PMID- 16944509
TI  - Effects of cadmium amendments on low-molecular-weight organic acid exudates in
      rhizosphere soils of tobacco and sunflower.
AB  - To recognize physiological response of plants to cadmium (Cd) toxicity in
      rhizosphere of plants, the pot experiments were employed to investigate how low
      molecular-weight organic acids (LMWOAs) were exudated from tobacco and sunflower
      roots of Cd-amended soils. The aims of this study were to assess the effect of
      LMWOAs on uptake of Cd by tobacco and sunflower under pot experiments, thus
      comparing the ability of tobacco and sunflower for phytoremediation. Surface
      soils (0-20 cm) were collected from Taichung Experiment Station (TC) (silty
      loam). Cadmium chloride (CdCl(2)) was amended into TC soil, giving Cd
      concentrations of 1, 5, 10 mg kg(-1) soil. Soils with different concentrations of
      Cd were put into 12 cm (i.d.) pots for incubation, and then 2-week-old tobacco
      and sunflower seedlings were transplanted into the pots. Tobacco and sunflower
      were grown in greenhouse for 50 days, respectively. The rhizosphere and bulk
      soils, and fresh plant tissues were collected after harvest. The Cd
      concentrations in the plant and transfer factor values in the sunflower were
      higher than that in the tobacco. No LMWOAs were detected by gas chromatograph in
      bulk soils, and low amounts of LMWOAs were found in uncontaminated rhizosphere
      soils. Acetic, lactic, glycolic, malic, maleic, and succinic acids were found in
      the tobacco and sunflower rhizosphere soils. Concentrations of LMWOAs increased
      with increasing amendment of Cd concentrations in tobacco and sunflower
      rhizosphere soils. Correlation coefficient (r) of concentrations of Cd amendment
      versus LMWOAs exudates of tobacco and sunflower were 0.85 and 0.98, respectively.
      These results suggest that the different levels of LMWOAs present in the
      rhizosphere soil play an important role in the solubilization of Cd that bound
      with soil particle into soil solution and then uptake by plants.

PMID- 16944510
TI  - Acute toxicity and bioaccumulation of aqueous and sediment-bound metals in the
      estuarine amphipod Melita plumulosa.
AB  - The sensitivities of juvenile and adult amphipods to metals (Cd, Cu, Ni, Pb, and
      Zn) in whole sediment and water-only exposures were compared using a newly
      developed acute test with the estuarine species Melita plumulosa. Endpoints
      included survival and bioaccumulation in adults, and survival and growth (body
      length) in juveniles over 96 h water-only and 10 day sediment exposures.
      Juveniles were more sensitive than adults to metals, either bound to sediments or
      in the aqueous phase. Although LOEC values for copper and zinc in juvenile whole
      sediment tests (820 and 2290 mg/kg dry weight, respectively) were high in
      comparison with interim sediment quality guideline values for individual metals
      (270 and 410 for copper and zinc respectively), they were generally within the
      range of concentrations found in contaminated sediments in local estuaries.
      Accumulation of metals, together with the low porewater metal concentrations in
      whole-sediment tests, indicated that the ingestion of sediment is an important
      source of zinc and copper and cause of toxicity in this species.

PMID- 16944511
TI  - Popliteal vein aneurysm due to an anomalous slip of the adductor magnus.

PMID- 16944512
TI  - Cadmium-induced changes in pigments, total phenolics, and phenylalanine ammonia
      lyase activity in fronds of Azolla imbricata.
AB  - This study was designed to examine the effects of cadmium on several color
      related parameters (including chlorophyll, carotenoid, and anthocyanin), total
      phenolics, and phenylalanine ammonia-lyase (PAL) activity in an aquatic fern
      species Azolla imbricate (A. imbricata). Cd accumulation and effects in the
      fronds were closely related with Cd concentration in the growth medium. The
      fronds under 0.5 mg/L Cd treatment turned red on the 3rd day, and this color
      change also appeared under 0.05 and 0.1 mg/L Cd treatment on the 5th day.
      Correlated with the color change, the contents of chlorophyll and carotenoid in
      the fronds significantly decreased in the presence of high Cd concentrations,
      while the anthocyanin content increased during the experiment. Significant
      increase in total phenolics content and PAL activity were also detected during Cd
      treatment. The results suggested that the Cd-induced change in color of fronds
      might be due to the decrease in chlorophyll and carotenoid and the increase in
      anthocyanin. Anthocyanin, total phenolics and their biosynthesis-related PAL
      might play a role in detoxification of Cd in A. imbricata.

PMID- 16944513
TI  - Effect of temperature on heavy metal toxicity to juvenile crayfish, Orconectes
      immunis (Hagen).
AB  - The acute toxicity of four selected heavy metals to juvenile crayfish Orconectes
      immunis (Hagen) (1-2 g wet body wt. each) at room temperature increased in the
      following order: cadmium (x3) < copper (x10) < zinc (x2) < lead. The toxicity of
      these metals to crayfish acclimated at 17, 20, 23/24, and 27 degrees C increased
      with temperature (by 7-20% between 20 and 24 degrees C and 14-26% between 20 and
      27 degrees C) as judged by the lowering of LT(50) (time to kill 50% of test
      animals at a fixed concentration) values. A 4 degrees C rise in temperature (from
      20 to 24 degrees C), which increased the toxicity of copper by about 7%,
      increased the rate of oxygen consumption by about 34%. Heavy metals inhibited the
      rate of oxygen consumption at all temperatures. In 20 degrees C-acclimated
      crayfish, copper caused about 17% inhibition of oxygen consumption compared to
      about 7-12% by other metals including the most toxic cadmium. A 3-4 degrees C
      rise in temperature tripled the inhibitory effect of copper (20%), cadmium and
      zinc (26 and 18%, respectively), but not of lead, on oxygen consumption. A 7
      degrees C-rise in temperature (from 20 to 27 degrees C) increased the inhibitory
      effect of heavy metals, including lead, on oxygen consumption by up to 54% in the
      case of copper. The data indicate that rising global temperatures (currently 0.60
      degrees C) associated with climate change can have the potential to increase the
      sensitivity of aquatic animals to heavy metals in their environment.

PMID- 16944514
TI  - Effects of copper pre-exposure routes on the energy reserves and subsequent
      copper toxicity in Daphnia magna.
AB  - The hypothesis was tested that copper uptake routes affect the tolerance of
      Daphnia magna to copper and influence the energy reserves. These were determined
      in D. magna juveniles that had been exposed for 4 days to water borne and/or
      dietary copper (algae Pseudokichneriella subcapitata loaded with copper) at
      nominal concentrations of 0, 10, and 100 nM. Tolerance increased with dietary
      copper pre-exposure reflected in 24 and 48 h LC50 values of 466 and 398 nM at 100
      nM pre-exposure versus 301 and 254 nM in controls, respectively. Control animals
      (no copper added to their exposure medium and diet) had the lowest lipid content
      and consequently the lowest energy content. The current study stresses the
      importance of addressing dietary exposure routes in metal toxicity assessments.

PMID- 16944515
TI  - Accessory middle cerebral artery originating from callosomarginal artery.

PMID- 16944516
TI  - Temporal and spatial changes in mercury concentrations in the North Atlantic as
      indicated by museum specimens of glacier lanternfish Benthosema glaciale (Pisces:
      Myctophidae).
AB  - Museum specimens of glacier lanternfish Benthosema glaciale were used to
      investigate long-term variations in mercury concentration of mesopelagic
      organisms from the North Atlantic. B. glaciale is an abundant mesopelagic fish
      species in the boreal and sub-polar pelagic regions of the North Atlantic,
      playing an important role in the cycling of energy in the oceanic food webs of
      these systems. We used 35 museum specimens of lanternfish, collected from the
      Gulf Stream biogeographic region between 1936 and 1993, to test for long-term
      variations in mercury concentrations. In addition, we studied the mercury
      concentrations throughout the geographical range of the species, using 105
      specimens collected around 1970s. Mercury concentrations were similar over time;
      however there was evidence of a noteworthy increase in mercury contamination
      during the World War II (1941) followed by a general decrease with lowest
      concentrations being found in 1954 and 1993. Significant differences were found
      between the different studied areas, probably reflecting different degrees of
      anthropogenic contamination. The results presented here indicate that museum
      myctophids may be suitable for the assessment of historical changes in mercury
      contamination of marine ecosystems.

PMID- 16944517
TI  - Study of the effects of Pb and Hg toxicity using a chronic toxicity reproductive
      5-day test with the freshwater rotifer Lecane quadridentata.
AB  - We have developed chronic toxicity reproductive 5-day tests to study the effects
      of Pb, as Pb(NO(3))(2), and Hg, as HgCl(2), exposure in the freshwater rotifer
      Lecane quadridentata. We used "r" (the instantaneous growth rate) as the
      endpoint. The test was performed using EPA medium at two food levels (10(5) and
      10(6) cells/mL of Nannochloris oculata) at a controlled temperature of 25 degrees
      C and an L/D cycle of 16:8 h. We monitored the levels of both metals, using
      atomic absorption, at days 0, 2, and 5 of each experiment. Our results showed
      that rotifers fed at higher food concentrations were capable of withstanding
      higher levels of metal toxicity than those fed at lower food concentrations (EC50
      = 0.704 versus 0.664 mg/L(-1) for lead, P < 0.05; EC50 = 0.057 versus 0.054 for
      mercury, P < 0.05). Our atomic absorption analysis showed that although 66% of
      lead nitrate can be taken up by algal cells efficiently and removed from the
      medium, rotifers also play an important role removing additional lead from the
      medium (up to 44% in some treatments). In the case of mercuric chloride, most of
      the mercury is bound by the salts contained in EPA medium or discarded by the
      organisms, and the remainder is removed by N. oculata in <48 h.

PMID- 16944518
TI  - Unusual termination of the great saphenous vein.

PMID- 16944519
TI  - Tuberculosis of the spine presenting with a cold abscess through the lumbar
      triangle of Petit.
AB  - The increasing incidence of human immunodeficiency virus (HIV) has resulted in an
      increase in the number of Mycobacterium tuberculosis (TB) infections worldwide.
      Musculoskeletal tuberculosis often involves the spine. Due to HIV, patients may
      present atypically and, as a result, a high clinical suspicion is necessary to
      avoid the catastrophic consequences of untreated Pott's disease of the spine. A
      cold abscess as a result of tuberculosis can emerge in a number of anatomical
      regions, and perhaps most notably as a psoas abscess. We report a less common
      anatomical location of a cold abscess, presenting as a mass in the inferior
      lumbar region through the lumbar triangle of Jean-Louis Petit. We consider the
      route that the pus had followed and highlight the need for vigilance when dealing
      with an abscess in this region, particularly in communities with a high incidence
      of HIV infection.

PMID- 16944520
TI  - Energetic aspects of locked nucleic acids quadruplex association and
      dissociation.
AB  - The design of modified nucleic acid aptamers is improved by considering
      thermodynamics and kinetics of their association/dissociation processes. Locked
      Nucleic Acids (LNA) is a promising class of nucleic acid analogs. In this work
      the thermodynamic and kinetic properties of a LNA quadruplex formed by the TGGGT
      sequence, containing only conformationally restricted LNA residues, are reported
      and compared to those of 2'-OMe-RNA (O-RNA) and DNA quadruplexes. The
      thermodynamic analysis indicates that the sugar-modified quadruplexes (LNA and O
      RNA) are stabilized by entropic effects. The kinetic analysis shows that LNA and
      O-RNA quadruplexes are characterized by a slower dissociation and a faster
      association with respect to DNA quadruplex. Interestingly, the LNA quadruplex
      formation process shows a second-order kinetics with respect to single strand
      concentration and has a negative activation energy. To explain these data, a
      mechanism for tetramer formation with two intermediate states was proposed.

PMID- 16944521
TI  - False tendons: an endoscopic cadaveric approach.
AB  - False tendons (FTs) have been extensively described and recognized by gross
      anatomic studies. However, in the clinical setting the recognition of FTs is
      limited to the use of echocardiography. We examined 200 formalin fixed adult
      hearts, with gross dissections. In addition, 90 of these specimens were also
      examined with ultrasonographic and endoscopic techniques. Gross examination was
      able to identify FTs in 128 (62%) specimens. The total number of FTs observed,
      was 248 and was classified into five types according to their location. In Type I
      (92, 37.1%) the FT was located between the posteromedial papillary muscle and the
      ventricular septum. In Type II (55, 22.1%) the FT was located between the two
      papillary muscles. Type III (41, 16.5%) was classified as an FT between the
      anterolateral papillary muscle and the ventricular septum. The FT in Type IV (31,
      12.5%) was observed to connect between the ventricular septum and the free wall
      and lastly in Type V (29, 11.6%) the FTs were found to be weblike with three or
      more points of insertion. When using all three techniques (n = 90), gross
      dissection and endoscopy were able to identify FTs in 62.2% of specimens while
      echocardiographic imaging was only able to identify FTs in 27.7% of specimens. Of
      the 114 FTs detected grossly and endoscopically, echocardiography was only able
      to identify 46 (40.3%). Therefore, the overall sensitivity of echocardiography
      for detecting left ventricular FTs was only 40.3%, compared to 100% for
      endoscopy. Based upon the ability or lack thereof of echocardiography to detect
      certain topographical patterns, we have created a small series of subtypes for
      the FTs. Histologically, in 30% of the FTs, conduction tissue fiber was observed
      to be present, which may implicate them in the appearance of arrhythmias.

PMID- 16944522
TI  - Deep fascia on the dorsum of the ankle and foot: extensor retinacula revisited.
AB  - This study revisits the anatomy of the deep fascia over the distal leg, ankle,
      and dorsum of the foot. The arrangement of the deep fascia in these regions was
      recorded in 14 lower limbs of adult cadavers using photographs and drawings. The
      fascial layer from all three sites was subsequently removed in toto, and serial
      thickness measurements were made along its entire length. In addition, fiber
      disposition was studied under polarized light, and sections were stained to
      demonstrate collagen. The arrangement of deep fascia is complex. A common and
      novel finding at all levels is a crisscross, lattice-like arrangement of fibers.
      There was little evidence of the clearly defined sturdy band of the superior
      extensor retinaculum (SER) or of the Y-shaped inferior retinaculum (IER) commonly
      illustrated in topographical anatomy texts. The SER is a complex area with
      several thickenings commencing about 3 cm proximal to the tip of the lateral
      malleolus and gradually increasing to reach a maximum of 270 microm about 5 cm
      above the malleolus, then gradually returning to original thickness, about 9 cm
      above the malleolus. Fibers crossing diagonally to each other are a feature of
      the region. The IER characteristically has two forms: either a cross-shaped band
      (9 specimens) or a thickened "node" with small extensions radiating toward the
      malleoli (5 specimens), located about 1-2 cm distal to the lateral malleolus and
      centred over the common tendon of extensor digitorum where it has maximum
      thickness (430 microm). The deep fascia is thickened and firmly attached over
      both malleoli and to the tarsals and metatarsals along both borders of the foot.
      In general, the deep fascial structures were thicker in males than those in
      females.

PMID- 16944523
TI  - Landmarks for the identification of the cutaneous nerves of the occiput and
      nuchal regions.
AB  - Although surgical procedures are often performed over the posterior head and
      neck, surgical landmarks for avoiding the cutaneous nerves in this region are
      surprisingly lacking in the literature. Twelve adult cadaveric specimens
      underwent dissection of the cutaneous nerves overlying the posterior head and
      neck, and mensuration was made between these structures and easily identifiable
      surrounding bony landmarks. All specimens were found to have a third occipital
      nerve (TON), lesser occipital nerve (LON), and greater occipital nerve (GON), and
      we found that the TON was, on average, 3 mm lateral to the external occipital
      protuberance (EOP). Small branches were found to cross the midline and
      communicate with the contralateral TON inferior to the EOP in the majority of
      sides. The mean diameter of the main TON trunk was 1.3 mm. This trunk became
      subcutaneous at a mean of 6 cm inferior to the EOP. The GON was found to lie at a
      mean distance of 4 cm lateral to the EOP. On all but three sides, a small medial
      branch was found that ran medially from the GON to the TON approximately 1 cm
      superior to a horizontal line drawn through the EOP. The GON was found to pierce
      the semispinalis capitis muscle on average 2 cm superior to the intermastoid
      line. The mean diameter of the GON was 3.5 mm. The GON was found to branch into
      medial and lateral branches on average 0.5 cm superior to the EOP. The LON was
      found to branch into a medial and lateral component at approximately the midpoint
      between a horizontal line drawn through the EOP and the intermastoid line. The
      main LON trunk was found on average 7 cm lateral to the EOP. In specimens with a
      mastoid branch of the great auricular nerve (GAN), this branch was found at a
      mean of 9 cm lateral to the EOP. The main trunk of this branch of the GAN was
      found to lie on average 1 cm superior to the mastoid tip. Easily identifiable
      bony landmarks for identification of the cutaneous nerves over the posterior head
      and neck can aid the surgeon in more precisely identifying these structures and
      avoiding complications. Although the occipital nerves were found to freely
      communicate with one another, avoiding the main nerve trunks could lessen
      postoperative or postprocedural morbidity. Moreover, clinicians who need to
      localize the occipital nerves for the treatment of occipital neuralgia could do
      so more reliably with better external landmarks.

PMID- 16944524
TI  - In response to Dr. Patel and Professor Moxham "Attitudes of professional
      anatomists to curricular change".

PMID- 16944525
TI  - Anatomic compartments of the foot: a 3-Tesla magnetic resonance imaging study.
AB  - There is neither consensus on the number nor agreement on the location of the
      anatomic compartments of the foot. This project utilized high-resolution magnetic
      resonance imaging (MRI) to identify foot compartments. The purpose of this study
      was to devise a new system using 3-Tesla (3T) MRI that assessed the number and
      location of these compartments. Six feet from healthy volunteers were imaged.
      From these, 10 compartments were described: (1) medial, (2) calcaneal, (3)
      lateral, (4) central superficial, (5) central deep (adductor), (6-9) interossei,
      and (10) skin. The 3T MRI and foot/ankle coil allowed us to assess the number and
      location of foot compartments.

PMID- 16944526
TI  - Some structures of the human body still remain controversial or incompletely
      described.

PMID- 16944527
TI  - Gliding characteristics of flexor tendon and tenosynovium in carpal tunnel
      syndrome: a pilot study.
AB  - The characteristic pathological finding in carpal tunnel syndrome (CTS) is
      noninflammatory fibrosis of the synovium. How this fibrosis might affect tendon
      function, if at all, is unknown. The subsynovial connective tissue (SSCT) lies
      between the flexor tendons and the visceral synovium (VS) of the ulnar
      tenosynovial bursa. Fibrosis of the SSCT may well affect its gliding
      characteristics. To investigate this possibility, the relative motion of the
      flexor tendon and VS was observed during finger flexion in patients undergoing
      carpal tunnel surgery, and for comparison in hands without CTS, in an in vitro
      cadaver model. We used a camera to document the gliding motion of the middle
      finger flexor digitorum superficialis (FDS III) tendon and SSCT in three patients
      with CTS during carpal tunnel release and compared this with simulated active
      flexion in three cadavers with no antemortem history of CTS. The data were
      digitized with the use of Analyze Software (Biomedical Imaging Resource, Mayo
      Clinic, Rochester, MN). In the CTS patients, the SSCT moved en bloc with the
      tendon, whereas, in the controls the SSCT moved smoothly and separately from the
      tendon. The ratio of VS to tendon motion was higher for the patients than in the
      cadaver controls. These findings suggest that in patients with CTS the synovial
      fibrosis has altered the gliding characteristics of the SSCT. The alterations in
      the gliding characteristics of the SSCT may affect the ability of the tendons in
      the carpal tunnel to glide independently from each other, or from the nearby
      median nerve. These abnormal tendon mechanics may play a role in the etiology of
      CTS.

PMID- 16944528
TI  - Incidence and ossification of sesamoid bones in the hands and feet: a
      radiographic study in an Arab population.
AB  - The incidence and ossification of sesamoid bones in the hands and feet were
      studied in 922 radiographs (400 hands and 522 feet) in an Arab population from
      Bahrain, 5-83 years of age and consisting of 549 adults (393 men and 156 women)
      and 373 children (286 boys and 97 girls). All radiographs of the hand and foot in
      the adult population showed two sesamoid bones in the thumb metacarpophalangeal
      (MCP) joint and in the hallucal metatarsophalangeal (MTP) joint, respectively.
      Only 2.3% and 1.5% of hands showed sesamoids at the MCP joints of the middle and
      ring fingers respectively compared to a reported incidence of 7.1% for each digit
      in Caucasians. The incidence of sesamoids in the MTP joints of third and fourth
      toes (0.6% each) and inferior to the hallucal interphalangeal joint (3.1%) is
      probably the lowest reported so far in the literature. In the hands, ossification
      commenced first in the thumb sesamoids, at the age of 10 years in females and 11
      years in males and was completed by the age of 13 and 14 years, respectively. In
      the feet, ossification began first in the hallucal sesamoids at the age of 8
      years in females and 9 years in males and was completed by the age of 10 years in
      both sexes. The incidence and ossification of sesamoids in the hands and feet in
      the Arab population from Bahrain seem to differ considerably from reports in
      other populations. The clinical significance of our findings is discussed.

PMID- 16944529
TI  - Posterior approach technique for accessory-suprascapular nerve transfer: a
      cadaveric study of the anatomical landmarks and number of myelinated axons.
AB  - Accessory-suprascapular nerve transfer by the anterior supraclavicular approach
      technique was suggested to ensure transferrance of the spinal accessory nerve to
      healthy recipients. However, a double crush lesion of the suprascapular nerve
      might not be sufficiently demonstrated. In that case, accessory-suprascapular
      nerve transfer by the posterior approach would probably solve the problem. The
      aim of this study was to evaluate the anatomical landmarks and histomorphometry
      of the spinal accessory and suprascapular nerve in the posterior approach.
      Dissection of fresh cadaveric shoulder in a prone position identified the spinal
      accessory and suprascapular nerve by the trapezius muscle splitting technique.
      After that, nerves were taken for histomorphometric evaluation. The spinal
      accessory nerve was located approximately halfway between the spinous process and
      conoid tubercle. The average distance from the conoid tubercle to the
      suprascapular nerve (medial edge of the suprascapular notch) is 3.3 cm. The mean
      number of myelinated axons of the spinal accessory and suprascapular nerve was
      1,603 and 6,004 axons, respectively. The results of this study supported the
      brachial plexus reconstructive surgeons, who carry out accessory-suprascapular
      nerve transfer by using the posterior approach technique. This technique is an
      alternative for patients who have severe crushed injury of the shoulder or
      suspected double crush lesion of the suprascapular nerve.

PMID- 16944530
TI  - Middle meningeal artery hemorrhage: an incorrect name.
AB  - Extradural hemorrhage is most commonly assumed to result from a middle meningeal
      artery rupture. This article challenges that assumption. The meningeal
      vasculature of 29 cadaveric specimens was examined macroscopically and
      microscopically at the level of the greater wing of the sphenoid bone and foramen
      spinosum. It was observed that the middle meningeal artery is accompanied by a
      pair of dural sinuses throughout the majority of its course, thus making
      exclusively arterial rupture an anatomical improbability. Furthermore, as these
      dural sinuses pass caudally through the foramen spinosum with the middle
      meningeal artery, they were seen to diverge to form a plexiform arrangement
      around the artery. This has not been reported before.

PMID- 16944531
TI  - Structural parameters of the vastus medialis muscle and its relationship to
      patellofemoral joint deterioration.
AB  - Vastus medialis (VM) muscle dysfunction and abnormal limb alignment are commonly
      observed in patients who experience changes in patellofemoral joint (PFJ)
      function, leading many clinicians to assume that there is a direct relationship
      between VM structural parameters, leg alignment, and PFJ dysfunction. This study
      tested the hypothesis that there is a relationship between structural parameters
      of the VM muscle, limb alignment, and the location and severity of patellofemoral
      joint deterioration (PFJD). The dissection study used 32 limbs from 24 intact
      cadavers. Data were collected on limb alignment, angle of VM muscle fibers below
      the superior aspect of the patella, length of VM inserting on the medial aspect
      of the patella, and severity and location of PFJD. Parametric and nonparametric
      statistical analyses illustrated that PFJD was most commonly located on the
      middle third of the medial half of the patellar articular surface. The severity
      of PFJD did not vary with location. There was no significant correlation between
      any of VM insertion length, VM fiber angle, limb alignment, and PFJD location and
      severity lpar;r(2) < 0.34). The results of this study did not support the
      hypothesis of a relationship between structural parameters of the VM muscle, limb
      alignment, and the location and severity of PFJD in this subject group. Future
      research should examine the relationship between functional parameters of the
      entire quadriceps muscle group and PFJ dysfunction.

PMID- 16944532
TI  - The keloid phenomenon: progress toward a solution.
AB  - For centuries, keloids have been an enigma and despite considerable research to
      unravel this phenomenon no universally accepted treatment protocol currently
      exists. Historically, the etiology of keloids has been hypothesized by multiple
      different theories; however, a more contemporary view postulates a multifactoral
      basis for this disorder involving nutritional, biochemical, immunological, and
      genetic factors that play a role in this abnormal wound healing. Critical to the
      process of preventing or managing keloids is the need to locally control
      fibroblasts and their activities at the wound site. In recent years, considerable
      evidence has accumulated demonstrating the importance of fatty acids and
      bioactive lipids in health and disease, especially those involving inflammatory
      disorders or immune dysfunction. If hypertrophic scarring and keloid formation
      can be argued to have significant inflammatory histories, then it is possible to
      postulate a role for lipids in their etiology and potentially in their treatment.
      This report briefly visits past views and theories on keloid formation and
      treatment, and offers a theoretical rationale for considering adjuvant fatty acid
      therapy for keloid management. Sufficient scientific evidence in support of fatty
      acid strategies for the prevention and treatment of keloids currently exists,
      which offer opportunities to bridge the gap between the laboratory and the
      clinic. The intent of this paper is to serve as a basic guideline for
      researchers, nutritionists, and clinicians interested in keloids and to propose
      new directions for keloid management.

PMID- 16944533
TI  - Leptomeningeal plaques, a "common" finding.

PMID- 16944534
TI  - Viable malignant germ cell tumor in the postchemotherapy retroperitoneal lymph
      node dissection specimen: can it be predicted using clinical parameters?
AB  - BACKGROUND: The presence of viable tumor in the surgical specimen after
      postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) is associated
      with an increased risk of disease progression. The objective of this study was to
      determine whether the presence of viable tumor in the surgical specimen could be
      predicted. METHODS: Between 1980 and 2003, 236 patients underwent PC-RPLND for
      clinical Stage IIA or III nonseminomatous germ cell tumors (NSGCT). The authors
      retrospectively reviewed the medical records of those patients for pertinent
      clinical and treatment-related outcomes. A multivariate logistic regression
      analysis was used to evaluate whether clinical parameters were capable of
      predicting the presence of viable tumor in the surgical specimen. RESULTS:
      International Germ Cell Consensus Classification (IGCCC) risk categories could be
      assigned to 218 patients, with 101 patients in the good-risk category, 32
      patients in the intermediate-risk category, and 85 patients in the poor-risk
      category. The incidence of viable tumor in the good-risk, intermediate-risk, and
      poor-risk categories was similar (17.8%, 15.6%, and 15.3%, respectively);
      however, the risk categories predicted disease-specific and recurrence-free
      survival (P = .022 and P < .0001, respectively). On multivariate analysis, an
      elevated serum alpha-fetoprotein (AFP) level prior to PC-RPLND (P = .05) and the
      size of the retroperitoneal mass on pathology review (P = .02) were predictive of
      viable tumor in the surgical specimen. CONCLUSIONS: Although IGCCC risk
      categories were correlated with disease-related outcomes, the risk groups had
      similar incidences of viable tumor. Elevated serum AFP levels prior to surgery
      and the size of the retroperitoneal mass in the resected specimen may help to
      predict viable tumor in the PC-RPLND specimen.

PMID- 16944535
TI  - Lysophosphatidic acid acyltransferase-beta (LPAAT-beta) is highly expressed in
      advanced ovarian cancer and is associated with aggressive histology and poor
      survival.
AB  - BACKGROUND: Lysophosphatidic acid acyltransferase-beta (LPAAT-beta) tumor
      expression is an emerging prognostic, diagnostic, and therapeutic target in early
      epithelial ovarian cancer (EOC). The significance of tumor overexpression of
      LPAAT-beta was investigated in a large number of advanced- and early-stage EOC
      patients. METHODS: LPAAT-beta expression was analyzed by immunohistochemistry
      (IHC) in 158 ovarian tumors, including 68 advanced and 90 low-stage tumors,
      representing all grades and histologies (including 33 borderline tumors). In
      advanced-stage patients, tissue from multiple sites was evaluated to assess
      differential expression of LPAAT-beta in local tumor and distant metastases.
      RESULTS: LPAAT-beta was overexpressed in 90 (57%) of all 158 ovarian tumors.
      Forty-nine (72%) of 68 advanced tumors overexpressed LPAAT-beta. LPAAT-beta was
      associated with the presence of carcinoma versus borderline histology (67% vs.
      18%, P < .0001), high histologic grade [according to the Silverberg Grading
      Scheme] (Grade 1, 25%; Grade 2, 21%; and Grade 3, 54%; P < .0001), and with
      papillary-serous histology. In an analysis of the 125 carcinoma patients, LPAAT
      beta increased with but was not significantly associated with advanced clinical
      stage (P = .1431). LPAAT-beta expression was associated with shortened
      progression-free survival (PFS) (5-year PFS, 32% for LPAAT-beta-positive vs. 60%
      for LPAAT-beta-negative; P = .0318) and decreased overall survival (OS) (5-year
      OS, 54% for LPAAT-beta-positive vs. 74% for LPAAT-beta-negative; P = .0173).
      CONCLUSIONS: LPAAT-beta is highly expressed in advanced ovarian tumors and is
      associated with aggressive histology and decreased PFS and OS. LPAAT-beta is an
      intriguing prognostic tool for the identification of high-risk EOC and a
      potential target for directed therapy that warrants further study.

PMID- 16944536
TI  - Biochemical and clinical significance of the posttreatment prostate-specific
      antigen bounce for prostate cancer patients treated with external beam radiation
      therapy alone: a multiinstitutional pooled analysis.
AB  - BACKGROUND: The posttreatment prostate-specific antigen (PSA) bounce phenomenon
      has been recognized in at least 20% of all patients treated with radiation. The
      purpose of the current report was to determine if there was a difference in
      biochemical and clinical control between the bounce and nonbounce (NB) patients
      using pooled data on 4839 patients with T1-2 prostate cancer treated with
      external beam radiation therapy (RT) alone at 9 institutions between 1986 and
      1995. METHODS: The median follow-up was 6.3 years. A posttreatment PSA bounce was
      defined by a minimal rise of 0.4 ng/mL over a 6-month follow-up period, followed
      by a drop in PSA level of any magnitude. Endpoints included no biochemical
      evidence of disease (bNED) failure (BF) (ASTRO definition), distant failure (DF),
      cause-specific failure (CSF), and overall survival (OS). Patients were stratified
      by pretreatment PSA, Gleason score, T stage, age, dose, and risk group. RESULTS:
      In all, 978 (20%) patients experienced at least 1 posttreatment PSA bounce.
      Within 3 subgroups (risk group, pretreatment PSA, and age), statistically
      significant differences of remaining bounce-free were observed on univariate
      analysis. Patients < 70 years had a 72% chance of remaining bounce-free at 5
      years compared with 75% for older patients (P = .04). The NB patients had 72%
      bNED control at 10 years compared with 58% for the bounce patients. The effect of
      a bounce remained statistically significant on multivariate analysis (P < .0001).
      No statistically significant difference in DF, CSF, or OS was observed.
      CONCLUSIONS: Patients treated with external beam radiation therapy alone who
      experience a posttreatment PSA bounce have increased risk of BF. However, this
      did not translate into a difference in clinical failure with the available follow
      up in the current study.

PMID- 16944537
TI  - The role of immunolocalization of CD57 and GLUT-1 in cell blocks in fine-needle
      aspiration diagnosis of papillary thyroid carcinoma.
AB  - BACKGROUND: CD57 (Leu7), a marker for natural killer lymphocytes, and glucose
      transporter-1 (GLUT-1), a facilitative cell surface glucose transport protein,
      are expressed in a wide spectrum of epithelial malignancies. The usefulness of
      CD57 and GLUT-1 immunostaining was evaluated as an adjunct to assist in the
      diagnosis of papillary carcinoma in fine-needle aspirations (FNAs) of the
      thyroid. METHODS: Immunohistochemical staining for CD57 and GLUT-1 was performed
      on paraffin-embedded cell blocks of 50 thyroid FNA cases with the following
      cytologic diagnoses: 1) papillary carcinoma (15 cases); 2) atypical cytology,
      cannot exclude papillary carcinoma (14 cases); and 3) benign thyroid (21 cases).
      RESULTS: Fourteen of 15 cases with an unequivocal diagnosis of papillary
      carcinoma were positive for CD57 and 1 case was negative for CD57. Tissue follow
      up confirmed papillary carcinoma in all 15 cases. Of the 14 cases with a
      diagnosis of atypical cytology, cannot exclude papillary carcinoma, 6 cases were
      positive for CD57 and subsequent excision confirmed papillary carcinoma in all 6
      cases. The remaining 8 cases negative for CD57 included surgically confirmed
      goiter (5 cases), adenoma (2 cases), and papillary carcinoma (1 case). The
      follicular cells in all 21 cases with a cytologic diagnosis of benign thyroid
      were negative for CD57. Histologic follow-up of these cases confirmed the benign
      cytologic diagnoses. GLUT-1 was negative in all cases. The sensitivity and
      specificity of CD57 was 91% and 100%, respectively. CONCLUSIONS: CD57
      immunostaining is a useful adjunct for the diagnosis of papillary thyroid
      carcinoma in cell block material. Although negative staining for CD57 does not
      completely exclude papillary carcinoma, positive staining aids in the accurate
      diagnosis of malignancy in cytomorphologically equivocal cases. GLUT-1 did not
      prove to be a useful marker in distinguishing papillary carcinomas.

PMID- 16944538
TI  - Fine-needle aspiration biopsy of non-Hodgkin lymphoma for use in expression
      microarray analysis.
AB  - BACKGROUND: The majority of patients with lymphoma undergo a single biopsy for
      diagnosis, and there are few opportunities to acquire posttreatment material.
      Fine-needle aspiration (FNA) biopsy is a minimally invasive procedure, and
      acquiring routine posttreatment material would require minimal effort and provide
      needed material for gene expression profiling. METHODS: Ex vivo FNA biopsies were
      performed using a standard clinical technique with 21-gauge, 22-gauge, 23-gauge,
      and 25-gauge needles for 8 lymph node specimens and were collected in either RNA
      stabilization reagent (RNAlater) or Trizol. Eight patients with known or
      suspected Non-Hodgkin lymphoma (NHL) underwent interoperative (in vivo) FNA
      biopsies based on the best technique derived from the ex vivo aspirates. RNA
      derived from the in vivo FNA biopsies and the matched, snap-frozen surgical lymph
      node biopsy remnant was used for gene expression analysis with proprietary U133A
      chips. RESULTS: The results confirmed the authors' experience, that RNA isolated
      from FNA biopsies of lymph nodes collected in Trizol is superior both
      quantitatively and qualitatively to RNA collected in RNAlater. Gene expression
      profiles of NHL derived from in vivo FNA biopsies and matched, frozen surgical
      specimens showed good overall correlation. CONCLUSIONS: High-throughput gene
      expression analysis in patients with NHL derived from material acquired by FNA
      biopsy is a feasible approach to developing a platform for real-time analysis of
      treatment responses in this group of patients.

PMID- 16944539
TI  - Surgical pathology stage by American Joint Commission on Cancer criteria predicts
      patient survival after preoperative chemoradiation for localized gastric
      carcinoma.
AB  - BACKGROUND: Preoperative chemoradiation for localized gastric cancer can modify
      baseline stage, as determined by surgical pathology stage. Therefore, the authors
      hypothesized that surgical pathology stage would be a better prognosticator of
      overall survival (OS) than baseline stage. METHODS: Patient populations were
      combined from 2 prospectively conducted, preoperative chemoradiation trials that
      used the same therapeutic strategy. Patients must have had localized gastric
      adenocarcinoma and were staged extensively, including endoscopic ultrasonography
      and laparoscopy. Patients had to be fit for surgery medically with a technically
      resectable cancer. All patients provided written informed consent. Patients first
      received induction chemotherapy for up to 2 months followed by chemoradiation (45
      grays) and an attempted surgery. OS was correlated with pretreatment and
      posttreatment parameters, including surgical pathology stage according to
      American Joint Commission on Cancer criteria. RESULTS: Of 74 patients who were
      registered, 69 patients (93%) had undergone surgery. Nineteen patients (26%) had
      a pathologic complete response (pathCR), and 55 patients (81%) had a curative
      (R0) resection. None of the pretreatment parameters correlated with OS; however,
      longer OS correlated with lower pathologic stage (P < .0001), R0 resection (P <
      .001), clinical response noted prior to surgery (P = .002), pathCR (P = .004),
      lower pathologic lymph node classification (P = .006), and lower pathologic tumor
      classification (P = .03). Pathologic stage and R0 resection were independent
      prognostic factors for OS (multivariate Cox model; both P = .05). CONCLUSIONS:
      When preoperative chemoradiation strategy was employed for gastric cancer, the
      surgical pathology stage, a reflection of cancer's biologic heterogeneity, was a
      better prognosticator of OS than the baseline clinical stage. Surgical pathology
      stage, in this setting, may serve as an intermediate endpoint for Phase II/III
      trials.

PMID- 16944540
TI  - Prevention of severe menorrhagia in oncology patients with treatment-induced
      thrombocytopenia by luteinizing hormone-releasing hormone agonist and depo
      medroxyprogesterone acetate.
AB  - BACKGROUND: Menorrhagia is a serious complication in young female oncology
      patients who suffer from severe thrombocytopenia during myelosuppressive
      treatment. To the authors' knowledge, little is known regarding the incidence of
      this complication or the effectiveness of possible therapies for its prevention.
      METHODS: In this retrospective clinical study, after a thorough gynecologic
      evaluation, young female oncology patients with regular menstrual cycles
      undergoing myelosuppressive treatments received either depo-medroxyprogesterone
      acetate (DMPA), or D-tryptophan-6-luteinizing hormone-releasing hormone depot
      treatment (gonadotropin-releasing hormone agonist [GnRH-a]), or no treatment
      before the administration of myelosuppresive chemotherapy. Only patients who
      later developed severe thrombocytopenia (<25,000 platelets per muL) were included
      in the study. Daily blood counts, menorrhagia, nonvaginal bleeding episodes, and
      the need for blood products, gynecologic consultations, and other medical
      interventions were determined. RESULTS: Of 101 women with cancer who met the
      inclusion criteria, 42 patients received DMPA, 39 patients received GnRH-a, and
      20 patients remained untreated. The mean duration (+/- standard deviation) of
      severe thrombocytopenia was 24.76 +/- 23.6 days. Four patients were not included
      because of significant gynecologic pathologies. General bleeding from
      nongynecologic sites was similar for all groups and was not associated with
      vaginal bleeding. Severe or moderate menorrhagia was documented in none of the 39
      women who received GnRH-a, in 9 patients (21.4%) who received DMPA, and in 9
      untreated patients (40%; P = .02). Fewer calls for urgent gynecologic
      consultations were documented in the GnRH-a group compared with the untreated
      group (P < .0001). CONCLUSIONS: Female patients undergoing myelosupressive
      therapy are at high risk of developing significant menorrhagia during prolonged,
      severe thrombocytopenia. Pretreatment gynecologic evaluation can detect
      significant pelvic pathologies. GnRH-a treatment effectively prevented
      menorrhagia, whereas DMPA administration was less effective.

PMID- 16944541
TI  - Predictors of outcome in patients undergoing postchemotherapy retroperitoneal
      lymph node dissection for testicular cancer.
AB  - BACKGROUND: The management of metastatic nonseminomatous germ cell tumors (NSGCT)
      frequently consists of systemic chemotherapy followed by retroperitoneal lymph
      node dissection (PC-RPLND). The aim of the present study was to evaluate the
      authors' PC-RPLND experience and identify predictors of outcome in these
      patients. METHODS: Between 1980 and 2003, 236 patients with clinical Stage IIA
      III NSGCT underwent PC-RPLND. Their medical records were retrospectively reviewed
      for pertinent clinical and treatment-related outcomes. The 5-year disease
      specific and recurrence-free survival was 85% and 75%, respectively, with the
      median length of follow-up after RPLND 45 months (6-250 months). RESULTS: The
      median age of patients at diagnosis was 28 years, with all patients receiving
      systemic chemotherapy (median of 5 cycles) before RPLND. On multivariate
      analysis, predictors of poorer disease-specific survival (DSS) included systemic
      symptoms at presentation (P = .05), elevated pre-RPLND serum alpha fetoprotein
      (AFP, P = .006) and beta-human chorionic gonadotropin (HCG, P = .004),
      postoperative complications (P = .03), and recurrence (P < .0001). Predictors of
      poorer recurrence-free survival (RFS) included advanced clinical stage (IIC-III,
      P = .001) and presence of viable tumor in the RPLND specimen (P = .03). A pre
      RPLND serum AFP > 9 ng/mL and HCG > 4.1 mIU/mL were found to predict a worse DSS
      (P = .03 and .03, respectively). CONCLUSIONS: In patients undergoing PC-RPLND,
      preoperative tumor markers and the occurrence of postoperative complications or
      recurrence are predictive of poorer DSS. Advanced clinical stage and viable tumor
      in the surgical specimen predict worse RFS.

PMID- 16944542
TI  - Synthesis, multiphase characterization, and helicity control in chiral DACH
      linked oligothiophenes.
AB  - A new class of chiral oligothiophenes is described. Mono-, bi-, ter-, and
      quarterthiophenes have been linked to enantiopure trans-1,2-cyclohexanediamine
      (DACH) via diamino or diimino moieties. The stereochemistry of DACH, the type of
      linker, and oligothiophene size determine the conformational flexibility of these
      molecules and consequently their molecular and supramolecular helicity in
      solution and in the solid state. The case of diaminobis(bithiophene), which
      inverts helicity and shows chiral amplification in the transition from solution
      to film, is described in detail. Based on the combined use of circular dichroism
      in solution and in the solid state, single-crystal/thin-film X-ray diffraction,
      and polarized optical microscopy, a working mechanism has been proposed to
      explain this unexpected behavior.

PMID- 16944543
TI  - Synthesis, structure, and in vitro antitumor activity of some glycoside
      derivatives of ferrocenyl-chalcones and ferrocenyl-pyrazolines.
AB  - Some new glycosides of 3-ferrocenyl-1-(4'-hydroxyphenyl)-prop-2-en-1-one were
      prepared and transformed into the corresponding pyrazoline and pyrazole
      derivatives. Using methyl-hydrazine, formation of regioisomers was observed. DDQ
      was found to be a mild and efficient reagent for the pyrazoline-pyrazole
      dehydroaromatization process. The structure of the new compounds was proved by IR
      and NMR spectroscopy. The in vitro antitumor activity of the substances was
      investigated against human leukemia (HL-60) cells by the MTT method. Among these
      new compounds some chalcone derivatives (3 a, 3 b, 5 a, and 5 b) showed
      attractive in vitro antitumor effects on human leukemia cells. These molecules
      contained ferrocenyl moieties and a p-hydroxy-phenolic ring or a size-independent
      apolar substitution of that.

PMID- 16944544
TI  - Activatable fluorescent probes for tumour-targeting imaging in live mice.

PMID- 16944545
TI  - 6-alkylthio-4-[1-(2,6-difluorophenyl)alkyl]-1H-[1,3,5]triazin-2-ones (ADATs):
      novel regulators of cell differentiation and proliferation.
AB  - Novel triazine analogues of 5-alkyl-2-alkylthio-6-[1-(2,6-difluorophenyl)alkyl]
      3,4-dihydropyrimidin-4(3H)-ones (F(2)-DABOs), previously described by us as
      nonnucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs), were tested for
      their antiproliferative and cytodifferentiating activity on the A-375 human
      melanoma cell line. Most of the tested derivatives were effective in decreasing
      cell proliferation, facilitating morphological differentiation, and reprogramming
      gene expression. All these effects were reversible upon withdrawal of RT
      inhibitors. Among the compounds tested, 3 f showed the highest antiproliferative
      effect, whereas compound 6 c, although not affecting cell proliferation, is
      endowed with a strong cytodifferentiating effect, which is probably related to a
      marked upregulation of the e-cad gene. These results support the potential of
      NNRTIs as valuable antitumor agents.

PMID- 16944546
TI  - Emerging and re-emerging viral infections in Europe.
AB  - Emerging viral infections are becoming a serious problem in Europe in the recent
      years. This is particularly true for severe acute respiratory syndrome (SARS),
      West Nile virus (WNV) disease, Toscana virus (TOSV) disease, and potentially for
      avian influenza virus (H5N1). In contrast, emergence or re-emergence of severe
      viral infections, including tick borne encephalitis virus, and viral haemorrhagic
      fever caused by Hantavirus and dengue virus have been frequently reported in
      several European countries. Laboratory diagnosis of these viral infections based
      on viral isolation or detection by immune electron microscopy, immunoassay and
      polymerase chain reaction (PCR) has dramatically improved in the recent years,
      and SARS represents a good example of a diagnostic approach to emerging viral
      infections. Finally, old and new promising agents are in the pipeline of
      pharmaceutical companies to treat emerging viral infections. However only
      prevention based on large epidemiological studies, and research and development
      of new vaccines may be able to control and eventually eradicate these deadly
      viral infections.

PMID- 16944547
TI  - The aftermath of Schiavo: advance directives update.

PMID- 16944548
TI  - Talking about...clinic.

PMID- 16944549
TI  - [Dialogue and interaction in psychotherapy].

PMID- 16944550
TI  - Profile: Ernst Wolner, MD.

PMID- 16944552
TI  - A rare clinical presentation of caudal brain stem lesion.

PMID- 16944553
TI  - Commercial support for professional development.

PMID- 16944554
TI  - [Image of the week. Eosinophilic cellulitis or Wells syndrome].

PMID- 16944555
TI  - Nature versus nurture: eugenics.

PMID- 16944556
TI  - American Academy of Psychiatry & the Law ethical guidelines for the practice of
      forensic psychiatry.

PMID- 16944557
TI  - AAPL's new ethics guidelines.

PMID- 16944559
TI  - Current awareness on yeast.

PMID- 16944558
TI  - Phagocytosis and hydrophobicity: a method of calculating contact angles based on
      the diameter of sessile drops.
AB  - The correlation between the contact angle and degree of phagocytosis of different
      yeast particles has been investigated. To facilitate the estimation of the
      contact angle, we have tested the hypothesis that the shape of a small liquid
      drop put on a flat surface is that of a truncated sphere. By making this
      approximation it is possible to calculate the contact angle, i.e. the tangent to
      the drop in the 3-phase liquid/solid/air meeting point, by measuring the drop
      diameter. Known volumes of saline were put on different surfaces and the
      diameters of the drops were measured from above. Calculation of the contact angle
      with drops of different volumes, and comparison between expected and measured
      height of 10 microl drops, indicated that the assumption that the shape of a drop
      is that of a truncated sphere is valid. Monolayers of leukocytes was shown to
      give rise to a contact angle of 17.9 degrees. Particles with a lower contact
      angle than the phagocytic cells resisted phagocytosis, but opsonization of the
      particles with normal human serum rendered them susceptible to phagocytosis,
      conferring a higher contact angle than that of the phagocytic cells.

PMID- 16944560
TI  - Male breast cancers in Pakistan.

PMID- 16944561
TI  - Practical ethics. To apologize or not, that is the question.

PMID- 16944562
TI  - Combating rising energy costs.

PMID- 16944563
TI  - Survey says hospitals must 'quickly transform' work environment to retain older
      nurses.

PMID- 16944564
TI  - Coalition releases set of seven standards for hospitals to better meet health
      needs of women.

PMID- 16944565
TI  - [Construction of RNAi binary vector of soybean receptor-like kinase gene (rlpk2)
      and its soybean transformation].
AB  - Plant receptor-like kinases (RLKs) play important roles in plant growth,
      development and responses to environmental stress. RNA interference (RNAi) is a
      powerful tool to study functions of RLKs. In this study, a 312bp 3'end cDNA
      fragment of the soybean receptor-like kinase gene rlpk2 was chosen to construct
      the rlpk2-RNAi expression cassette. The binary vector pART27-R2 harboring rlpk2
      RNAi expression cassette was constructed through three times subcloning via mid
      clone vector and then transformed into Agrobacterium LBA4404. Three independent
      transgenic plants were obtained by Agrobactium-mediated soybean cotyledon
      transformation method. RT-PCR analysis showed that rlpk2 gene was successfully
      knocked down in all transgenic plants. It was found that photosynthesis
      activities of rlpk2-RNAi transgenic leaves were much improved, suggesting rlpk2
      may function as a negative regulator of soybean leaf functions and/or chloroplast
      structure.

PMID- 16944566
TI  - [Construction of HPV type 16 Li antigen expressing tumor model].
AB  - Recombinant expression vector was constructed by techniques of gene
      recombination, and identified by restriction endonuclease and sequence analysis.
      Then the recombinant was transfected into B16 cell by techniques of gene
      transfection and expressions were detected by RT-PCR and IFA. After that,
      transfected cells were inoculated into subcutaneous of mouse and the forming
      tumor and expression of HPV16L1 protein after tumor was formed was observed.
      Identification of pcDNA- HPV16L1 by enzyme digestion showed that the length,
      inserted location and direction of the target gene which was inserted into the
      recombinant was correct and the expression of L1 in transfected cell was observed
      by IFA. The inoculated cells could form tumor in vivo obviously and HPV16 L1
      protein could express in the cells stably.

PMID- 16944567
TI  - [Chemokine CXCL16 induces proliferation and invasion of human first-trimester
      cytotrophoblasts in autocrine manner].
AB  - To investigate the secretion and autocrine roles of chemokine CXCL16 in first
      trimester human cytotrophoblast cells, enzyme-linked immunosorbent assay (ELISA)
      was used to detect the CXCL16 secretion of primary-cultured cytotrophoblast cells
      in various lengths of culture time and various plated densities in vitro. Then,
      the [3H] thymidine incorporation assay and matrigel invasion assay were applied
      respectively to investigate proliferation and invasion roles of CXCL16 on the
      cytotrophoblast cells treated with rhCXCL16. Our results showed that the primary
      cultured cytotrophoblasts were found to secrete in vitro CXCL16 spontaneously and
      continuously. CXCL16 stimulated the proliferation and invasion of cytotrophoblast
      cells in vitro. These results indicated that CXCL16 is secreted in first
      trimester cytotrophoblast cells and induces the proliferation and invasion of
      cytotrophoblast cells in autocrine manner. CXCL16 plays important roles in human
      placentation and extravillous trophoblast invasiveness.

PMID- 16944568
TI  - [Cloning and expression analysis of human N-acetyltransferase doman containing
      gene hNATL].
AB  - A novel human gene hNA TL (Human NAT Like) was cloned by in silico cloning and RT
      PCR. hNA TL cDNA is 1803bp in length with a 621bp coding region, and the Genbank
      accession No. is AY632082. hNA TL encodes a protein of 206 amino acid residues
      which containing a N-acetyltransferase domain. hNA TL is located on human
      chromosome 17q25.2 with 6 exons. Serial analysis of gene expression revealed that
      hNA TL was highly expressed in human brain and gonad, while hNA TL was expressed
      in heart, spleen and gonad of adult mouse. Whole-mount in situ hybridization
      showed that hNATL specifically expresses in E7.5 and E8.5 mouse embryo brains and
      in HH10 stage chicken embryo brain. These results suggest that hNATL may play an
      important role in the development of embryo brain and may also be important for
      function of adult brain and gonad.

PMID- 16944569
TI  - [Calcium distribution in the egg cell, zygote and proembryo of lettuce (Lactuca
      sativa L.)].
AB  - Potassium antimonite precipitation was used to located calcium in the egg cells
      (before and after anthesis), zygotes and proembryos of lettuce (Lactuca sativa
      L.). A few calcium precipitates (ppts) were located in the small vacuoles of
      cytoplasm of egg cell at 3 d before anthesis, when egg cells just formed. Then
      the small vacuoles fused to form some bigger vacuoles in egg cell at 2d before
      anthesis. Calcium ppts increased evidently in the cytoplasm and nucleus of egg
      cells at this time. At 1d before anthesis, a biggest vacuole located at the
      micropyle end of the cell and its nucleus was pushed toward the chalazal end of
      the cell, which made an evident cellular polarity. The number of calcium ppts in
      the egg cell markedly decreased, suggesting that change of calcium distribution
      may be related to the development of egg cell. After anthesis and before
      fertilization, calcium ppts were still few in the egg cells, and most of them
      were accumulated in the nucleus, especially in the vacuoles of nucleolus. At 4h
      after anthesis, egg cell was fertilized and the wall at the chalazal end of egg
      cell was formed completely. Calcium ppts evidently increased again in egg cell,
      and some big ppts appeared in the karyoplasm of nucleus and abundant small ppts
      in the large vacuole. At 9h after anthesis, zygote completed its first division.
      Calcium ppts in the nucleus and cytoplasm of two-celled proembryo began to
      decrease, and only some ones accumulated in the vacuoles of nucleolus. At 18h
      after anthesis, zygote divided several times and became a multi-celled proembryo.
      Calcium ppts in the cells of proembryo ulteriorly diminished but there were many
      ppts on the surface of proembryo. The result indicates that calcium in egg cell,
      zygote and the cells of proembryo orderly changes its temporal and spatial
      position, which suggests that calcium may play a role during the development of
      egg cell and zygote.

PMID- 16944570
TI  - [Nuclear gene involves in phenotype of non-syndromic deafness associated with
      mitochondrial 12S rRNA mutation].
AB  - The human mitochondrial 12S rRNA gene mutation at position 1555 associated with
      non-syndromic deafness and aminoglycoside-induced deafness. Family of Huaiyin in
      Jiangsu is one of the biggest non-syndromic deafness family in the world. In this
      family, deafness is maternally inherited. After establishing immortal
      lymphoblastoid cell lines of the family by EB virus, we analysed 17
      lymphoblastoid cell lines derived, respectively, from symptomatic, asymptomatic
      and controll members of the family. Compared with control members, symptomatic
      and asymptomatic members both exhibited significant decreases in the rate of
      growth as well as in the rates of mitochondrial protein synthesis. But the extent
      of decreases is different and the severity of mitochondrial defect is related
      with its clinical phenotype. These results supported that the nuclear factor
      involves in the phenotypic manifestation of the non-syndromic deafness associated
      with the A1555G mutation.

PMID- 16944571
TI  - [Study on the correlation between the expressions of nm23H1 mRNA, VEGF-C mRNA and
      lymphatic metastases, survival rate with gastric cancer].
AB  - The correlations between the expression of nm23H1 mRNA,VEGF-C mRNA, VEGFR-3 and
      neoangiogenesis, hyperplasia of micro-lymphatic, tumor metastases in gastric
      cancer were studied, the results supplied an experimental foundation for clinical
      treatment and prognosis. All the specimens were marked by VEGFR-3 antibody, the
      expressions of nm23H1 mRNA, VEGF-C mRNA were detected in 78 cases of gastric
      cancer in situ hybridization with EnVision and Leica-Qwin computer image analysis
      system. The Weidner's highest vessel density counting method was used to analyse
      micro-lymphatics count (MLC) of the specimens, and the patients' viability after
      operation was investigated. The positive expression of nm23H1 mRNA in gastric
      cancer was 69.23% (54 cases). There was negative correlation between the positive
      expression of nm23H1 mRNA and lymph node metastasizing, TNM staging, MLC (P <
      0.01 or P < 0.05). The expression of VEGF-C mRNA was 46.15% (36 cases). It was
      positive related to the lymph node metastasis, TNM stages, MLC in gastric cancer
      (P < 0.01 or P < 0.05), and was significantly different compared with adjacent
      nontumorous tissue (P < 0.01 or 0.05). The expression of nm23H1 in stage I and II
      gastric cancer was high, while in stage III and IV the expression was lower or
      even none. The MLC (8.37 +/- 2.29/mm2) in gastric cancer was higher than that in
      adjacent nontumorous tissue (4.82 +/- 3.48/mm2), which has statistical
      significance (P < 0.05). There was negative correlation between the expression of
      nm23H1 mRNA and VEGFR-3 (p < 0.05, r = 0.8479), but positive correlation between
      VEGF-C mRNA and VEGFR-3 (P < 0.05, r = 0.8362). The MLC (10.82 +/- 2.51/mm2) in
      those who died in five years (48 cases) was higher than that (6.53 +/- 2.09/mm2)
      in those who were still alive, the difference has statistical significance (P <
      0.05). In different tumor pathology grading, different differentiation, the
      nm23H1 positive expression is significantly different (P < 0.05). Higher the
      nm23H1 expressed, lower the tumor lymph metastasized, but the viability rate was
      higher, so the nm23H1 gene was thought to have the effect of suppressing gastric
      cancer occurring and lymph metastasizing. Higher the VEGF-C mRNA expressed,
      higher the tumor lymph metastasized, but the viability rate was lower. There is
      close correlation between the VEGFR-3 expression and gastric cancer lymph
      metastasizing. The higher MLC level indicated neoangiogenesis in gastric cancer.
      VEGF-C promote neoangiogenesis induced by tumor and play an important role in
      lymph metastasizing.

PMID- 16944572
TI  - [Ultracytochemical studies of aloin in Aloe arborescens leaves].
AB  - Lead acetate precipitation method was used for ultracytochemical localization of
      aloin. The processes of aloin production, transport and storage were studied by
      transmission electron microscope. Results showed that aloin was produced in the
      plastids of the assimilating tissue. The aloin was transported through the
      plastid membrane to the surrounding endoplasmic reticulum and enveloped in the
      vesicles by the endoplasmic reticulum elements, the vesicles approached and later
      fused with the plasmalemma. Some vesicles of the plastid membrane directly fused
      with the plasmalemma. The vesicles released their contents into the apoplast
      through exocytosis, and finally reached the vascular bundle sheath by apoplastic
      translocation. Aloin was transported to the internal tangential wall of vascular
      bundle sheath cell through endoplasmic reticulum vesicles, and reached the
      cytoplasm of aloin cell by means of plasmodesmata. Finally, aloin was stored in
      the vacuoles of aloin cell.

PMID- 16944573
TI  - [Coding-sequence mutation and polymorphism analysis of EDNRB gene in patients
      with Hirschsprung's disease from Zhejiang region].
AB  - To determine the characters of EDNRB gene in patients with sporadic
      Hirschsprung's disease (HD) and discuss the relationship between mutation of
      EDNRB gene and HD, seventy five sporadic HD cases and forty normal cases as
      control were collected and DNA was extracted from peripheral white blood cells by
      standard method. All seven exons of EDNRB gene were analyzed by single strand
      conformation polymorphism analysis of polymerase chain reaction products (PCR
      SSCP) and direct sequencing. In result, A G --> A transition in codon 277 was
      observed in exon 4 in six patients. This variation leads to a nonsense mutation
      (L277L) and is a previously described polymorphism, the rate of variation is 8%
      (6/75). A G --> A transition in codon185 was detected in exon 2 in two patients,
      this is a novel heterozygous mutation, leading to a missense mutation (V185M),
      and the rate of mutation is 2.7% (2/75). So we can conclude that mutation of
      EDNRB gene can be detected in Chinese patients with sporadic HD and EDNRB gene
      might play an important role in the pathogenesis of HD.

PMID- 16944574
TI  - [Cytological and embryological observation on the cross of autotriploid x diploid
      in rice].
AB  - In this report, the process of hybridization between different ploidy levels was
      observed in rice. Autotriploid (2n = 36) 149-B, generated naturally from the twin
      seedling rice population SAR-2, was used as the female parent crossing with a
      normal diploid variety Shuhui 363. The processes of fertilization and
      embryological development were investigated. The pollen could germinate in
      triploid tissue of pistil normally and arrive at micropyle. But the percentage of
      double fertilization was only 8.89%, and the percentage of seed setting was
      0.566%. The hybridization obstacles mainly occurred in the process of
      fertilization. Barriers of double fertilization, prolongation and abnormal
      development of proembryo, and even development stopping or differentiation
      failure of embryo and/or endosperm could result in abnormal development and
      abortion of zygote.

PMID- 16944575
TI  - [Culture of soybean somatic embryo line and stability of microsatellite DNA].
AB  - We cultured soybean immature cotyledons to induce somatic embryos and set up
      soybean somatic embryo lines by culturing the induced somatic embryos in liquid
      medium on shaker. Regenerated plants of normal fertility were easily obtained
      with the cultures of various ages by culturing the somatic embryos on
      differentiation media. DNAs were isolated from the embryogenic cultures after 5,
      9, 15 or 17 months' suspension and from 42 plants regenerated from somatic
      embryos of various culturing ages. 102 SSR markers covering soybean genome almost
      evenly were chosen to check variation of microsatellite DNA during suspension
      culture and differentiation. Among the eight DNA samples of soybean somatic
      embryos of various ages and 42 DNA samples of regenerated plants, there was no
      any variation of the major bands of the 102 SSR markers during one year's
      subculturing and differentiation. There were only six weaker subsidiary bands of
      five SSR markers among the 102 SSR markers added in four of the fifty DNA
      samples. Two of them happened to the same regenerated plant differentiated from
      the 9-month embryogenic cultures. Three happened to the two DNA samples from
      somatic embryos irregular in morphology of the 5-month embryogenic cultures. The
      last subsidiary band variation happened to a DNA sample of the 17-month
      embryogenic cultures. The results show that stable microsatellites were
      maintained during the suspension culture and differentiation while we made the
      cultures highly embryogenic potential and easy to regenerate.

PMID- 16944576
TI  - [Molecular adjuvant C3d up-regulates both B7-1 and B7-2 expression on Raji
      cells].
AB  - To explore modulation of the molecular adjuvant C3d in the hCGbeta -C3d3 fusion
      protein in costimulatory molecule expression on Raji cells by linking to the
      surface molecule CD21. Raji cells, B cell line, were incubated with the purified
      hCGbeta-C3d3, hCGbeta or C3d3 protein for 15 hours respectively in the
      interference of anti-CD21 monoclonal antibody or not. The culture concentration
      of each group was 10, 30, or 90 microg/ml respectively. The expression of both B7
      1 and B7-2 on Raji cells were analyzed by flow cytometric assay. It was observed
      that compared to hCGbeta or C3d3 protein, hCGbeta-C3d3 up-regulated both B7-1 and
      B7-2 expression on the Raji cells, and the effect was in a dose-dependent manner.
      The up-regulation effect was blocked efficiently by anti-CD21 mAb. The results
      showed that molecular adjuvant C3d may up-regulate both B7-1 and B7-2 expression
      on Raji cell via C3d/CD21/CD19 complex, thus enhance the antigen presentation of
      B cell, and the interaction between B cell and T cell.

PMID- 16944577
TI  - [Study on factors influencing Agrobacterium-mediated transformation of Jatropha
      curcas].
AB  - Susceptibility of explants to antibiotics and the transient expression of beta
      glucuronidase (GUS) gene were studied to determine the optimal conditions for
      gene transformation of Jatropha curcas mediated by Agrobacterium Tumefaciens. The
      results showed that Jatropha curcas was insensitive to the antibiotic cefotaxime,
      which is used for suppressing the growth of Agrobacterium after cocultivation,
      while the plant was sensitive to kanamycin, hygromycin, phoshpinothrincin. All
      the three selective reagents synchronously suppressed the induction and the
      growth of callus, shoot organogenesis in a dose-dependent manner. The types of
      explants and the physiological state of the explants had strong influence on the
      transient expression efficiency of GUS. Hypocotyl, cotyledon petiole and
      cotyledon from 14-day-old seedling were more susceptible to Agrobacterium
      infection. Hygromycin-resistance calli from cotyledon explants were obtained and
      showed GUS staining.

PMID- 16944578
TI  - [Cloning and identification of the resistance gene analogs of wheat].
AB  - Specific primer sequences were designed on the basis of converse motifs of cloned
      resistance genes and subsequently used as PCR primers to amplify the resistance
      gene analog (RGA) in wheat (Triticum aestivum L.) Xinong 88 which possesses rust
      disease resistance. The amplified products of WRGA1, WRGA2 and WRGA14 were cloned
      and sequenced. The wheat RGAs contain some conserved motifs such as Kinase-2a,
      Kinase-3a and HD presenting in known NBS-LRR resistance genes from other plants
      and share between 46.0%-9.9% amino acid sequence identity with them. The amino
      acid sequence identity among three RGAs is 80.7%-56.8%. The WRGA1 expression was
      induced and detected by Northern blotting, which is positively regulated by
      salicylic acid.

PMID- 16944579
TI  - [SSR polymorphism on the waxy gene locus and their relationship to amylose
      content in wheat].
AB  - Variation of one simple sequence repeat (SSR)(AT (AT)n AT) in the 3 end of the
      waxy gene was analyzed in samples of 32 cultivars, including different wheat
      cultivars in Shandong region and representing a wide distribution range of
      amylose content (AC) in cultivated wheat. In this study, we found two fragments
      were present in all cultivars, one of 204bp, the expected size, and one of 225
      346bp. 204bp fragment located on the chromosome 7DS, while 225-346bp fragment
      located on the chromosome 7AS. That is, Wx-Ala gene and Wx-Dla gene present in
      all wheat lines, but the larger fragment showed length polymorphism. The result
      showed that the amylose level is highly positive correlated with the length of
      the polymorphic SSR. Amplified fragment is long in high AC cultivars and
      electrophoresis migration rate is small, while the fragment is short in low AC
      cultivars and electrophoresis migration rate is large. AC is highly diverse among
      different lines with the various SSR genotypes. Although the SSR variation did
      not seem to have obvious function in the synthesis of the starch synthase encoded
      by the waxy gene, the correlation between the SSR and AC level could be used as
      molecular marker for quality improvement in wheat programs.

PMID- 16944580
TI  - [The features of distribution of polysaccharide and lipid in the developing
      anther of Lycium barbarum L].
AB  - Polysaccharide and lipid in the anthers of Lycium barbarurn L. at different
      stages were examined with cytochemical techniques. At the stage of sporogenous
      cell, many starches have been storied in parenchyma around vascular bundle,
      epidermis and endothecium cells but no starches in sporogenous cells, tapetal and
      middle layer cells. At the stage of tetrad, there were many starches still in
      epidermis and endothecium, however tapetal cells began to accumulate lipid drops,
      suggesting that tapetal cells transformed polysaccharides into lipid. Tapetum
      degenerated at the late stage of microspore and the lipid drops moved into
      locule. During microspore development neither starches nor lipid drops were
      accumulated in the cell. After the division of microspore, some lipids drops
      appeared in 2-cellular pollen, and then some starches also appeared in the
      pollen. Two days before anthesis, there were many lipid drops and starches
      located in nearly mature pollen grains, suggesting that pollen of Lycium
      barbarurn L. has a function of transforming lipid into polysaccharide. The
      temporal and spatial features of polysaccharide and lipid material accumulated
      and distributed in anther during its development reflect the transformation of
      physiological function of the cells consisting of anther. This research will help
      us to understand the mechanism of anther development.

PMID- 16944581
TI  - [Regulation of vitality and IL-10 receptor expression of human decidual stromal
      cells in early pregnancy by IL-10, IFN-gamma].
AB  - The study is to investigate the effect of IL-10, IFN-gamma on viability and IL-10
      receptor expression of human decidual stromal cells (DSC) in early pregnancy. The
      vitality of DSC was detected by MTT. IL-10R1 and IL-10R gene expression of DSC
      were detected after treated by different concentrations of IL-10, IFN-gamma at
      15min, 30min, 45min, 60min. The vitality of DSC was significantly enhanced by the
      higher dose of IL-10 (100-10ng/ml) (P<0.05), and there was no significant
      stimulative role induced by the lower dose of it(0.10-1ng/ml)(P>0.05). The
      viability of DSC was inhibited by the highest dose of IFN-gamma (1000ng/ml)
      (P<0.01), on the contrary, its viability was stimulated by the lower dose of IFN
      gamma (10ng/ml) (P<0.05). IL-10R1 was highly expressed by IL-10 of 10ng/ml within
      15min, and significantly reduced at 30min, then disappeared within 45min; while
      IL-10R1 expression was not induced by IL-10(1ng/ml) of lower concentration
      throughout 60min; IL-10R1 was briefly and lowly expressed by IFN-gamma of
      100ng/ml, which effect on DSC at 45min; The expression of IL-10R1 was moderate
      level induced by IFN-gamma of 10ng/ml within 30min,and reduced at 45min,then
      disappeared at 60min. There was no significant difference of IL-10R2 expression
      (P>0.05) between treatment and not with the above-mentioned cytokines. IL-10, IFN
      gamma may play an important role of immune regulation in early pregriancy by
      influencing IL-10R1 expression and vitality of DSC.

PMID- 16944582
TI  - [siRNA-cyclin D1 inhibit cell proliferation in breast cancer MCF-7 cell line].
AB  - To study the inhibitory effect of siRNA on cyclin D1 expression and cell
      proliferation in breast cancer MCF-7 cell line. The siRNA targeting cyclin D1 was
      chemically synthesized and transfected into MCF-7 cells by oligofectamine. The
      expression of cyclin D1 was analyzed by quantitive PCR and Western blot, and the
      cell growth inhibition was measured with CCK-8 assay. Then, cell cycle of the
      transfected cells was examined by flow cytometry, and cell colony forming ability
      was measured by soft-agar colony formation assay. After MCF-7 cells were
      transfected with 10, 50, 100nmol/L siRNA,the expression of cyclin D1 mRNA was
      respectively suppressed with inhibition rates of 57.85%, 63.22% and 68.02%, and
      the protein expression was suppressed with inhibition rates of 51.13%, 62.09% and
      77.68% respectively. The proliferation of MCF-7 cells was inhibited after
      transfection with siRNA-cyclin D1, which caused cell cycle arrest at G1 phase and
      showed less colony forming ability in the breast cancer cell line MCF-7. These
      results indicate that siRNA-cyclin D1 could be a powerful anti-proliferative tool
      in breast cancer gene therapy.

PMID- 16944583
TI  - [Uterine expression of adenovirus E4 promoter-binding protein 4 (E4BP4) during
      the embryo implantation period in mice].
AB  - Adenovirus E4 promoter-binding protein 4 (E4BP4), a mammalian basic leucine
      zipper (bZIP) nuclear transcription factor, was identified to be involved in cell
      survival and proliferation. Previous research data showed that the expression of
      E4BP4 gene was up-regulated at the implantation sites on day 5 pregnancy of
      mouse. The aim of the present study was to examine the expression pattern of
      E4BP4 gene in uterus during pre-implantation period, and at the implantation
      sites and inter-implantation sites during the implantation process, through the
      Northern blot, in situ hybridization, Western blot and immunohistochemistry
      analyses. It was found that, (1) during the pre-implantation period, the
      expression of E4BP4 gene was gradually increased; (2) its expression was sharply
      up-regulated at the implantation sites compared with that at the inter
      implantation sites during the embryo implantation process; (3) the uterine
      expression of E4BP4 gene was not embryo-dependent, but observed in artificially
      induced decidulization of pseudopregnant mouse; (4) both E4BP4 mRNA and E4BP4
      protein were localized in stromal cells and decidual cells around the uterine
      lumen. These results indicated that E4BP4 may play a critical role in embryo
      implantation process by promoting stromal cell proliferation and inhibiting
      decidual cell apoptosis.

PMID- 16944584
TI  - [Study on the mitochondrial inner membrane potential of apoptotic thymocytes at
      cell and organelle level].
AB  - In this study, dexamethasone was used to induce mouse thymocyte apoptosis. The PI
      and Annexin V/PI staining flowcytometry methods were adopted to detect late and
      early phases apoptosis. Inner mitochondrial membrane potential (deltapsim) was
      examined by JC-1 and DiOC6(3)/PI staining flowcytometry. Direct JC-1 staining
      technology was applied to test the of deltapsim abstracted pure mitochondria.
      Results showed: DEX could significantly induce late and early phase mouse
      thymocyte apoptosis; at cell level, DEX was observed to reduce staining ability
      of deltapsim dependant fluorescence, J-aggregate and DiOC6(3), to drop down
      mitochondria number, but to cause no significant change of cell membrane
      integrity. Results of pure mitochondria detection showed most of them maintained
      normal deltapsim. According to above results, we concluded DEX could reduce
      mitochondria number when inducing mouse thymocyte apoptosis; and the remaining
      ones maintain normal function to meet the energy need for apoptotic process.

PMID- 16944585
TI  - [Initial identification of quantitative trait loci controlling resistance to
      banded leaf and sheath blight at elongating and heading date in maize].
AB  - The genetic linkage map was constructed with 146 SSR markers based on a maize
      population consisting of 229 F2 individuals from the cross R15 (resistant) x 478
      (susceptible), covering 1666cM on a total of ten chromosomes, with an average
      interval length of 11.4 cM. The disease index from the population of 229 F24
      lines were evaluated for BLSB resistance under artificial inoculation at
      elongating stage and heading date. With the method of composite interval mapping
      (CIM) described in QTL cartographer v2.0 procedure, 9 QTLs among of 17 QTLs were
      identified on 1, 2, 3, 4, 5, 6 and 10 chromosomes at Jointing Stage, accounting
      for 3.72% to 9.26% of the phenotypic variance. The other 10 QTLs were identified
      on 2, 3, 4, 5, 6, 8 and 9 chromosomes at elongating stage and heading date,
      accounting for 4.27% to 9.27% of the phenotypic variance. Among of them, two QTLs
      were detected at two stages, which were located between bnlgl600-umc1818 and
      umc1006-umc1723 on chromosome 2 and 6, respectively. The result indicated that
      the significant difference about QTL Controlling Resistance between the two
      stages had a close connection with Developing Stages, which was showed on the
      resistance of banded leaf and sheath blight in maize. So this result provided new
      information to the resistance breeding of maize.

PMID- 16944586
TI  - [Effects of different donor cells and passages on the development of nuclear
      transfer porcine embryos].
AB  - This study was undertaken to systematically examine effects of different donor
      cells and passages on the development of nuclear transfer porcine embryos, so as
      to establish a preliminary procedure for porcine cloning. Porcine oocytes
      obtained from ovaries at slaughter were matured in vitro for 40-44h and then
      enucleated in manipulation medium containing 5 microg/mL cytochalasin B.
      Fibroblast cells (FC), oviduct epithelial cells (OEC), granulosa cells (GC) and
      cumulus cells(CC) after 3-9 passages in TCM + 10% FBS were treated by serum
      starvation (0.5% FBS for 2-9 days), 0.1 microg/mL aphidiconlin (APD) for 1 day
      and 0.5% FBS for 2-9 days or continue culturing in 10% FBS for 2-9 days, then,
      were transferred into enucleated oocytes by microinjection or electronic fusion
      (100 V/mm, 30 micros and 1 pulses). Reconstituted embryos were activated with a
      combination of calcium ionophore A23187 or electric pulse and 6-DMAP, and
      cultured for 6 days, to evaluate their cleavage and embryonic development. The
      cleavage rate of embryos reconstructed with FC and GC pretreated with 0.1
      microg/mL APD + 0.5% FBS were significantly higher than that of serum starvation
      group and control group (P<0.01). There was significantly difference in the
      cleavage rate and embryonic development among embryos derived from GC, CC and FC,
      OEC pretreated with 0.1 microg/mL APD + 0.5% FBS. The cleavage rate of embryos
      reconstructed with GC by electrofusion was significantly higher than that by
      microinjection (P<0.05), but no difference was found in their proportion
      developing to blastocysts. 75% to 85% of GC at 3 and 6 passages, and FC at 6 and
      10 passages had normal karyotype, which did not show significant difference among
      them (P>0.05). When GC at G3, G4, G5 and G6 of passages were used as donor cells,
      the cleavage rate and blastocyst rate was similar, moreover, FC at G6, G7, G8 and
      G9 of passages also resulted in a similar cleavage rate and blastocyst
      development. These results indicate that: (1) FC and GC can be cultured up to 9
      passages and keep relatively stable karyotepe; (2) Using 0.1 microg/mL APD to
      treat donor cells prior to nuclear transfer can improve the efficiency of somatic
      cell nuclear transfer in buffalo but serum starvation is inefficient in our
      system; (3) Both of FC and GC cells can be used as the donor karyoplasts for
      nuclear transfer, and their efficiency are not influenced by the culture
      passages; (4) The development of reconstructed embryos by electrofusion is higher
      than that by microinjection, but there is no difference in the total efficiency
      between the two methods.

PMID- 16944587
TI  - [In vitro study on proliferation and multi-lineage differentiation potential of
      adipose-derived cells].
AB  - Adipose were obtained from patients underwent liposuction treatment (total 19
      female donors, 31.5 +/- 5.8 years old). Liposuction tissues were digested with
      type I collagenase, cells were isolated and cultured up to passage 10. To
      evaluate the proliferation potential of ADCs, growth curve and cumulative
      population doubling were achieved by cell counting. CD29,CD105, CD106, CD166,
      CD49d, CD34, CD31, 3G5 were analyzed by flow cytometry and immunocytochemistry to
      characterize the cell population. The multi-lineage potential of ADCs was
      testified by differentiating cells with osteogenic,chondrogenic and adipogenic
      inducer. A total of 5x10(7) nucleared cells could be obtained from 300ml
      liposuction tissues. After in vitro cultivation,cumulative population doubling
      number reached 15.53 at passage 10 (average 1.59 +/- 0.224 /passage). Flow
      cytometry and immunocytochemistry showed that ADCs expressed high level (>60%) of
      stem cell-related antigen (CD29, CD105, CD106, CD166), while cells expressed
      hematopoiesis-related antigen CD34 and CD31 around 7.3% and 29.2% respectively.
      Collagen II (both in mRNA and protein level) was detected in chondrogenic
      differentiation. The calcified nodules were observed by von Kossa and Alizarn Red
      staining and the expressions of AKP and Osteonectin were detected by RT-PCR in
      osteogenic differentiation. PPARr2, GLU-4, and Leptin genes were detected in
      adipogenic differentiation and intracellular lipid droplets could be observed by
      Oil Red staining. ADCs can be abundantly harvested and have high proliferative
      and multi-lineage differentiation potential.

PMID- 16944588
TI  - Identification and genetic mapping of a novel gene involved in pollen development
      in arabidopsis.
AB  - With an aim of the genetic dissection of anther and pollen development, we
      identified an Arabidopsis mutant line named zy1511 by ethyl-methane sulphonate
      (EMS) mutagenesis. Genetic analysis indicated that the mutant phenotype was
      controlled by a single recessive nuclear gene zy1511. Cytological studies of
      anther at various developmental stages indicated that the mutant anther tapetum
      did not start degenerating after microspores released from the tetrads. Part of
      the mutant anther tapetum still existed at late stages of anther development,
      indicating that mutant tapetum degenerated later than that of the wild-type. So
      the mutant microspores could not develop into normal pollen grains in the anther.
      For the further genetic analysis and the map-based cloning of gene zy1511, we
      have mapped it to a region of 134 kb between molecular markers F25P12 and T8L23
      on chromosome 1 using a map-based cloning strategy. As no male sterile genes have
      been reported in this region, we believe that zy1511 is an undiscovered key gene
      involved in pollen development.

PMID- 16944589
TI  - [Changes of nuclear matrix proteins during differentiation of human osteosarcoma
      MG-63 cells induced by HMBA].
AB  - Human osteosarcoma MG-63 cells were induced into differentiation by hexamethylene
      bisacetamide (HMBA). Its nuclear matrix proteins were selectively extracted, and
      subjected to two dimensional gel electrophoresis analysis. The resulted protein
      patterns were analyzed by Melanie software. There were 12 spots changed
      remarkably during the differentiation induced by HMBA, nine of which were
      identified. The up-regulated proteins were identified as MHC class II antigen,
      interferon-stimulated gene factor 3d, hypothetical protein DKFZp434M2221.1,8
      hydroxy-guanine glycosylase homolog ogg1, and vimentin. The down-regulated ones
      were hnRNP A2/B1 and actin; and two newly expressed proteins under induction were
      60S ribosomal protein L21 and ST2 protein. This study suggests that the induced
      differentiation of carcinoma cells is accompanied with changes of nuclear matrix
      proteins, and confirms the presence of some specific nuclear matrix proteins
      associated with carcinoma cell growth and differentiation. The changed nuclear
      matrix proteins are potential markers for cancer diagnosis or targets for cancer
      therapy.

PMID- 16944590
TI  - [The ultrastructure of compound eye in the Portunus tritubereulatus under
      different wavelength lights adaptation].
AB  - The fine structure of compound eye in Portunus tritubereulatus under different
      wavelength lights adaptation was studied with electron microscopy. The Portunus
      tritubereulatus were trained in a darkroom for 30 minutes and they were given the
      lights of different wavelength (red 750 nm, yellow 580 nm, green 560 nm, blue 400
      nm). The result showed that fine structures varied with different wavelength
      lights. Under red light, the diameter of rhabdom was biggest, the microsvilli was
      orderly. There were more endoplasmic reticulum and mitochondria in the cell. The
      pigment granules were distributed everywhere in the cytoplasm. The dimension of
      perirhabdomal vacuoles was small. Under blue light, the diameter of rhabdom was
      smallest, the microsvilli was messy. There were more lamellar bodies, lysosomes
      and perirhabdomal vacuoles in the cell. The pigment granules were distributed
      around nucleolus.

PMID- 16944591
TI  - [Detection of rpoB gene mutations in Mycobacterium tuberculosis].
AB  - ABSTRACT With Mycobacterium tuberculosis H37Rv as a control, the mutations of
      rpoB gene from 37 Mycobacterium tuberculosis clinical isolates (18 rifampin
      resistant strains and 19 rifampin-susceptible strains) have been detected by
      polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP) under
      standard condition (no glycerol in gel). For the strains in which mutations had
      not been detected under standard condition, PCR-SSCP analysis was performed again
      on condition that 8% glycerol was added to gel. In addition, the PCR products of
      rpoB genes of 30 strains (18 rifampin-resistant strains and 12 rifampin
      susceptible strains) were detected by DNA sequencing. After twice analyses of PCR
      SSCP, in 18 rifampin-resistant strains, the patterns of 17 strains were found to
      be abnormal; and in 19 rifampin-susceptible strains, the patterns of 16 strains
      were found to be normal. Compared with routine drug susceptibility test, the
      sensitivity of PCR-SSCP 94.4% is higher for rifampin resistance detection, and
      specificity of PCR -SSCP 84% seems lower. The results of sequence analysis were
      shown as: amomg 18 rifampin-resistant strains, only one has deletion in codons
      513 and 514 of rpoB gene, which is a new report, the others have point mutation;
      among 12 rifampin- susceptible strains, 3 positive strains in SSCP occur gene
      mutations directly related to rifampin resistance. Then compared with DNA
      sequencing, the accuracy, sensitivity and specificity of PCR-SSCP are 96.7%,
      95.2% and 100% respectively. Therefore, the sensitivity of mutation detection in
      SSCP could be improved by adding glycerol in gel. It is feasible and efficient to
      detect the mutation of rpoB gene in Mycobacterium tuberculosis by PCR-SSCP. This
      method is valuable to evaluate the rifampin resistance of Mycobacterium
      tuberculosis in clinical application for curing tuberculosis.

PMID- 16944592
TI  - [Protoplast culture and plant regeneration of the methionine resistant variant of
      Astragalus cicer L].
AB  - A protoplast-to-plant system for the methionine resistant variant of Astragalus
      cicer L. has been developed. The friable calli induced from stem segments of
      variant plants were used as materials for protoplast isolation through enzyme
      digestion. The effects of different media and plating densities on protoplast
      divisions and plant regeneration were studied. Sustained cell divisions and
      colony formation from the protoplasts of the methionine resistant cell line of
      Astragalus cicer L. were obtained by a DPD medium containing 2.0 mg/L 2,4-
      dichlorophenoxyacetic acid (2,4-D), 0.2 mg/L 6 -benzylaminopurine(6-BA), 0.3
      mol/L mannitol, 200 mg/L casein hydrolysate and 2% (W/V) sucrose at a plating
      density of 2x10(5) /ml. The division frequency was 38.3%. At the same time,
      different dividing types of protoplasts were found. Organogenesis and shoot
      formation from the protoplast-derived calli were induced on MS medium
      supplemented with 0.5 mg/L NAA, 10 mg/L KT and 2% (W/V) sucrose. The protoplast
      derived calli still expressed resistance to methionine. The protoplast to plant
      regeneration protocol developed in this study might provide the foundation for
      the resistant cell line as a parent for somatic hybridization.

PMID- 16944593
TI  - [Analysis of shoot apical anatomic changes during the development of Brassica
      plants].
AB  - In this study, we analyzed shoot apical anatomic changes during the development
      of Brassica plants including cauliflower (Brasscia oleracea L.var. botrytis),
      broccoli (B. oleracea L.var italica), Chinese cabbage (Brasscia compestris spp.
      pekinensis) and cabbage (Brasscia oleracea.L.). It has been showed that all of
      their apical meristems changed from the original tunica-corpus structure to the
      intergrade subarea, to typical 5-subarea structure and to 4-subarea structure
      when they went into reproductive development. The shoot apical meristem (SAM)
      cells were undergoing in different developmental way among these plants after
      they began reproductive development. The bilateral cells of sub-tunica of Chinese
      cabbage and cabbage divided into apical leafy primordial, in which lateral
      inflorescence meristem arised. While the bilateral cells of sub-tunica of
      cauliflower and broccoli divided into inflorescence meristem, which proliferated
      into curd or head. The results presented here provide the base for further
      investigation of anatomic identity of inflorescence phenotype formation and
      molecular events associated with meristem fate.

PMID- 16944594
TI  - Cloning and characterization of a novel soybean receptor-like protein kinase gene
      GmRLCK.
AB  - Protein kinases play key roles in transduction of both environmental and
      developmental signals in higher plants. Here reported full-length cDNA cloning
      and preliminary structural and functional analysis of a novel soybean receptor
      like protein kinase (RLK) gene (GenBank Accession No.AY687390). The deduced
      protein product of this gene contains a transmembrane region, an intracellular
      catalytic domain possessing serine/threonine kinase activity, and an
      extracellular domain which lacks the N-terminus signal peptide. Bioinformatic
      analyses revealed highly similarity between this soybean gene and a group of the
      Arabidopsis RLK genes which all lack of N-terminus signal sequence and belong to
      RLCK subfamily. Thus, it was designated GmRLCK. Some residues of GmRLCK that
      showed high probability to be phosphorylated were also predicted. RT-PCR analysis
      revealed higher expression levels of GmRLCK in soybean cotyledons, roots, flowers
      and young pods; whereas lower expression levels were detected in radicles, stems
      and mature leaves at vegetative stage. Phylogeny analysis suggested that GmRLCK
      was more close to and might have a common ancestor with several senescence
      associated RLKs.

PMID- 16944595
TI  - Diagnostic detection and genetic analysis of wheat stripe rust resistant gene
      YrCN19.
AB  - DNA samples of 19 wheat cultivars or lines were screened with the primer pair
      Xgwm410, a diagnostic marker of wheat stripe rust resistant gene YrCN19. The
      results showed that the wheat cultivars or lines CN19, XK5, AIM5 and AIM6
      produced the amplicon Xgwm410/391, which co-segregated with the resistance of
      YrCN19, but other cultivars or lines did not produced it. Pedigree analysis and
      resistance test showed that CN19, XK5, AIM5 and AIM6 carried wheat stripe rust
      gene YrCN19. Genetic analysis proved that the resistance to wheat stripe rust of
      CN19, XK5, and AIM5 inherited in single dominant gene genetic law (3 resistant: 1
      susceptible). The results also proved that the resistance descent in the cross
      combination Yanfu188/AIM6 complied with the single dominant gene genetic law (3
      resistant: 1 susceptible), while the resistance inheritance in other cross
      combinations (CN18/AIM6, Lu955159/AIM6 and Shu3110/ AIM6) complied with two gene
      complementary genetic law (9 resistant: 7 susceptible). The results suggested
      that the resistance expression and separation of YrCN19 was distinct in the
      various genetic backgrounds or cross combinations. This study would expedite the
      exploitation and utilization of YrCN19 in wheat resistant breeding.

PMID- 16944596
TI  - [The effects of prenatal stress on Ca2+ channel and K+ channel of hippocampal CA3
      pyramidal neurons in rat offspring].
AB  - To investigate the effects of prenatal stress (PNS) on high-voltage-activated
      (HVA) Ca2+ channel and delayed rectifier potassium currents (I(KD)) of freshly
      isolated rat offspring hippocampal CA3 pyramidal neurons, the pregnant rats of
      PNS group were exposed to restraint stress and patch clamp technique of whole
      cell mode was employed to record HVA Ca2+ and K+ channel currents in hippocampal
      CA3 pyramidal neurons. It was observed that PNS increased HVA calcium peak
      current amplitude. The maximal HVA calcium peak current amplitudes were -576.52
      +/- 7.03 pA in the control group and -702.05 +/- 6.82 pA in the PNS group
      respectively (P < 0.01). The conductance-voltage relationship of HVA Ca2+ channel
      was not changed. Current-voltage relationship and conductance-voltage
      relationship of I(KD) in offspring CA3 neurons were also not affected by PNS. The
      data suggested that exposure of pregnant animals to a period of stress could
      impose lasting effects on the offspring hippocampus CA3 neurons Ca2+ channel
      during a critical phase of fetal development. The mechanism may include two ways.
      One was that high CORT led to enhance level of expression for the HVA Ca2+
      channel subunit mRNAs and increased HVA calcium currents. Another was that PNS
      caused an increase in the production of ROS in hippocampal CA3 region and ROS
      caused an increase in the phosphorylation of HVA Ca2+ channel of offspring
      hippocampal CA3 neurons.

PMID- 16944597
TI  - [The production and distribution of the newborn neural precursor in the
      telencephalon of female Melanocorypha mongolica and compared with female Lonchura
      striata].
AB  - The production of labeled precursors in adult female Melanocorypha mongolica and
      Lonchura striata were investigated by using bromodeoxyuridine (BrdU) and ABC
      immunohistochemical method to mark new synthesized DNA. Then, the distribution of
      newborn precursor was compared between the two kinds of songbirds. The results
      reveal that: 1) During 1-4 days after BrdU intramuscular injection, there were a
      great number of labeled cells in lateral ventricular zone (LVZ),and forming
      proliferation 'hot spots' in the ventricular zone (VZ) of the ventral striatum
      and neostriatum. The newborn labeled precursor in the two adult songbirds
      originated from ventricular zone in telencephalon. In the two adult songbirds,
      there were a great number of labeled precursors in the ventricular zone (VZ) of
      the medial striatum and lateral striatum and forming proliferation 'the first hot
      spots'; in the top of LVZ and forming proliferation 'the second hot spots'. In
      Melanocorypha mongolica,there were a lot of labeled precursors in the tail of VZ
      in lateral striatum and forming proliferation 'the third hot spots'. But in
      Lonchura striata, there were a small number BrdU labeled precursors in the tail
      of VZ. 2) From 5 days after BrdU intramuscular injection in Melanocorypha
      mongolica, a great number of labeled precursors in the LVZ began to migrate into
      the other region of the telencephalon. During 5-30 day after BrdU intramuscular
      injection, some of labeled cells emerged into the nucleus of high vocal center
      (HVc), and robust nucleus of the archistriatum (RA) in Melanocorypha mongolica.
      But there were no BrdU labeled cells in the HVc and RA in female Lonchura striata
      during the 30 days after BrdU intramuscular injection. New neurons, which are
      added to HVc and RA continuously in adult female Melanocorypha mongolica, may be
      necessary for learning the new songs of adult male birds. HVc and RA of adult
      Lonchura striata have few new neurons to replace older neurons.

PMID- 16944598
TI  - [Identification and analysis of the specific molecular marker associated with
      fertile maintenance of cytoplasmic male sterility cauliflower].
AB  - Analysis of RAPD (Randomly Amplification Polymorphic DNA) was performed between
      cytoplasmic male sterility line and its maintainer line of cauliflower. Totally
      2160 detectable bands were obtained by RAPD using 406 10-bp random primers.
      Averagely, 5 to 10 bands were produced per primer. Among all the primers only the
      amplification of primer S2121 was polymorphic in two lines. A 934-bp specific
      band was only detected in maintainer line. After cloning and sequencing, specific
      primers were designed to transform the RAPD marker to PCR marker, which was named
      S2121(900). To identify the specificity of S2121(900), southern dot blotting was
      performed. To further identify its specificity, individual plant and candidate
      materials testing were also performed. All these results indicated that the
      S2121(900) was specific. It can be used to screen the maintainer lines of
      cauliflower in early stage. Analysis of the sequence suggested that this fragment
      was high homologous with the part sequences of mitochondrial genome in Brassica
      napus and Arabidopsis thaliana. So we supposed the S2121(900) may also derive
      from mitochondrial genome. Our results here offer new clues for explaining the
      molecular mechanism of cytoplasic male sterility of cauliflower in other way.

PMID- 16944599
TI  - [Vitrification of mouse blastocyst by open pulled straw (OPS) method at different
      temperature].
AB  - To examine the efficiency of EDFS and EFS for blastocyst cryopreservation and to
      provide information for preparation of vitrification medium at different
      temperature, the present investigation was conducted to establish a model for
      vitrification of domestic animal's blastocyst and human blastocyst using mouse
      blastocyst as a model and OPS (open pulled straw) as the container. When ambient
      temperature was 25 degrees C and heating plate temperature was 37 degrees C,
      mouse blastocysts were vitrified using 1-step OPS method, after thawing, the
      expanded blastocyst (EB) rates of EDFS40 and EFS40 group (92.31%, 92.30%) were
      not different from that of the control (97.26%) (P > 0.05), however, the hatched
      blastocyst (HB) rate of EDFS40 group (59.62%) was significantly lower than that
      of the control (83.56%); When 2-step method was adopted at the same temperature,
      mouse blastocyst was successfully cryopreserved with EDFS30 and EFS40, the post
      thawing EB rate (95.69%, 95.05%) and HB rate(80.48%, 78.95%) of both EDFS30 and
      EFS40 groups did not differ from those of the control (P > 0.05). When ambient
      temperature was 25 degrees C and heating plate was free, the EB rate (85.96%) and
      HB (75.44%) of embryos vitrified with EDFS40 using 1-step OPS method were not
      statistically different from those of the control (96.05% and 82.89%,
      respectively) (P > 0.05); the EB and HB rates (92.03%-95.31%, 67.19%-76.76%) of
      embryos vitrified with EDFS30, EDFS40 and EFS40 using 2-step OPS method were
      similar to those of the control (P > 0.05). According to in vitro development of
      vitrified embryos, the promising group was chosen for embryo transfer to examine
      in vivo development of vitrified embryos. When vitrified blastocysts were
      transferred into uterus of pseudopregnant mouse, the pregnancy rate of receipts
      (90.90%) and birth rate of foster mother (37.33%) were similar to those of fresh
      embryos (91.67% and 42.33%) (P > 0.05). All data demonstrated that mouse
      blastocyst was successfully cryopreserved with EDFS30, EDFS40 and EFS40 at
      different temperature and using different procedures.

PMID- 16944600
TI  - [Study on genetic instability of nm23H1 gene in Chinese with original gallbladder
      tumor].
AB  - The aim of this study was to examine the microsatellite instability (MSI) and
      loss of heterozygosity (LOH) of locus D17S396 on chromosome 17 and their
      influence on the expression of nm23H1 in gallbladder tumors, which may provide
      experimental basis for the tumor occurrence and metastasis. Techniques such as
      DNA extraction from formalin-fixed paraffin-embedded tissues, polymerase chain
      reaction-single strand conformation polymorphism (PCR-SSCP), ordinary silver
      stain were used to study MSI and LOH of locus D17S396. Envision
      immunohistochemistry and Leica-Qwin computer imaging techniques were used to
      assess the expression of gene nm23H1. In our experiment, the frequency of genetic
      instability of malignant gallbladder tumors was 42.55%, which was higher than
      that of gallbladder adenomas, while there were no genetic instability occurred in
      chronic cholecystitis tissue. The frequency of LOH seemed higher with the
      deteriorism of gallbladder tumor. Among 47 gallbladder carcinomas, the frequency
      of LOH and MSI were different between different differentiation cases (P < 0.05),
      and the frequency of LOH in liver and lymph node metastasis cases was
      significantly higher than those without metastasis (P < 0.01). Moreover, the
      frequency of LOH was higher in stage Nevin IV and V when compared with stage I,
      II and III. However, the frequency of MSI showed contrary correlation with some
      clinicopathologic characteristics. The expression of nm23H1 in gallbladder
      carcinoma, gallbladder adenoma and chronic cholecystitis tissue were different (P
      < 0.05). The case with lymph node metastasis showed significantly lower nm23H1
      expression than those without lymph node metastasis (P < 0.01). Nevin stage IV
      and V also exhibited lower nm23H1 expression levels compared with stage I, II and
      Ill. Furthermore, there was no difference in nm23H1 protein expression intensity
      analyzed by computer imaging techniques. In gallbladder carcinomas, the positive
      frequency of nm23H1 protein in LOH positive group was lower than that of LOH
      negative group (P < 0.05). The results indicated that the genetic instability of
      nm23H1 gene might be implicated in pathogenesis and progression of gallbladder
      tumor. Both MSI and LOH of nm23H1 gene controlled the development of gallbladder
      tumor independently in different paths. MSI may be an early stage molecule marker
      of gallbladder carcinoma. LOH may be molecule marker for the deteriorism of
      gallbladder tissue, which could inhibit the expression of nm23H1 in local tissue
      of gallbladder carcinoma and endow it with high aggressive and poor prognosis.
      Increasing the amount of nm23H1 protein expression could effectively restrain
      gallbladder carcinoma metastasis and improve prognosis of patients.

PMID- 16944601
TI  - [Analysis of changes about hsbp1, hsf1, hsf2 AND hsp70's expression levels in
      rat's regenerating liver].
AB  - Heat shock factor binding protein 1 (HSBP1), a recently discovered protein,
      weakens and blocks transcription of the heat shock protein 70 (HSP70) gene when
      binding to HSF1, but HSBP1 can promote cell growth, cell development and cell
      differentiation when binding to HSF2. Partial hepatectomy (PH) in rat creates
      injury stimulation and induces liver regeneration. How does hsbp1 coordinate two
      processes sequently is extremely interesting. This paper, based on cloning the
      full-length cDNA of hsbpl in rat, applied in situ hybridration and Rat Genome 230
      2.0 Array to analyze hsbp1, hsf1, hsf2 and hsp70 expression in liver after PH and
      sham-operation. The results indicated that the hsbp1 expression level was down
      regulated meaningfully at 0.5-2h and up-regulated meaningfully at 8-16h after
      sham-operation, while hsf2 expression level did not meaningfully change at 0-144h
      after sham-operation. hsbp1 expression level was up-regulated meaningfully at 6h
      and 66-144h,and hsf1 at 8-16h, hsf2 at 2-16h, hsp70 at 0.5-24h after PH. Our data
      suggested that up-regulated expression of the hsp70 at 0.5-12h after sham
      operation was controlled by intracellular HSF1, and then controlled by hsbp1 down
      regulated at 0.5-2h and hsf1 up-regulated at 8-16h. In the early phase of liver
      regeneration in rats, hsbp1 and hsf2 expression levels were up-regulated, which
      promoted cell proliferation through HSBP1 and HSF2 up-regulating,upa activating,c
      jun enhancing, intracellular matrix (ECM) degradation, activating the hepatocyte
      like growth factor (HGF) etc. In the late phase of liver regeneration (66-144h),
      hsbp1 expression level was up-regulated, which promoted reconstruction of liver
      structure and recovery of liver function through HSBP1 inhibiting hsp70
      expression, up-regulating genes related to growth, development, differentiation.
      In conclusion, down-regulating of hsbp1 contributed to interaction between HSF1
      and HSE,increased hsp70 expression and enhanced anti-injured capacity of liver
      and rats. HSBP1 and HSF2 activated the genes related to growth, development,
      differentiation and then promoted liver regeneration in rats.

PMID- 16944602
TI  - [Changes of Smad2 and type I collagen expressions on cultured human Tenon's
      capsule fibroblasts transfected with Smad7 vector].
AB  - The purposes of this research is to investigate Smad2, phosphorylated Smad2 (p
      Smad2) and type I collagen expressions in the cultured human Tenon's capsular
      fibroblasts (HTFs) transfected with Smad7 vector and to elucidate the mechanism
      of Smad7 in blocking tissue fibrosis after filtration surgery. Nucleofector was
      used to transfect Smad7 vector into HTFs. Reverse transcription real-time
      quantitive polymerase chain reaction (real-time RT-PCR) was then used to detect
      Smad7 mRNA expression levels. The expressions of HA-probe fusion protein, Smad2,
      p-Smad2, alpha2-type I procollagen (COL1A2) mRNA and carboxyterminal propeptide
      of type I procollagen (PICP) were determined by real-time RT-PCR, Western blot,
      cellular immunofluorescence assay and radioimmunoassay. The items mentioned above
      were also detected after HTFs being stimulated by TGF-beta2 (10 ng/ml). HTFs and
      vector-HTFs were used as control groups. Clones with Smad7 overexpression were
      successfully established. Results of real-time RT-PCR proved that there was no
      difference of Smad2 mRNA between Smad7 overexpression clone and the control
      groups whether stimulated by TGF-beta2 or not. The increase of p-Smad2 expression
      stimulated by TGF-beta2 was inhibited in Smad7 overexpression clone by Western
      blot assay. It only took 56.01% and 53.48% of control groups. In cellular
      immunofluorescence assay, the p-Smad2 positive cells in Smad7 overexpression
      clone only took 31.02% and 29.41% of control groups. Smad7 -HTFs could also
      abolish the increase of COL1A2 mRNA expression and PICP concentration stimulated
      by TGF-beta2. It is possible that Smad7 can block the signal transduction of TGF
      beta by downregulating the expression of p-Smad2 in HTFs. However, it doesn't
      affect the expression of Smad2.

PMID- 16944603
TI  - [Efficient plant regeneration in vitro in Pinus massoniana L].
AB  - Pinus massoniana L. is one of the important trees for afforestation in South
      China. The efficient system of plant regeneration from mature zygotic embryos and
      seedlings of masson pine was established in this study. The influences of basal
      media, hormones and methods for buds induction, shoots elongation and rooting
      were studied. The results indicate that DCR medium with 0.5 mg/L BA and 0.05 mg/L
      IBA shows the highest differentiation rate of adventitious buds. Induction and
      multiplication of axillary buds take aseptic seedlings as explants. KT has better
      effect than BA on the axillary buds induction. The best axillary buds induction
      medium is DCR medium supplemented with 1 mg/L KT and 0.2 mg/L IBA. After
      culturing on GD medium with 0.1 mg/L BA and 0.2 mg/L IBA for elongation, the buds
      were transferred on the 1/2 GD medium with 2 mg/L IBA and 0.05 mg/L BA for
      adventitious roots induction. Paraffin slice indicates that the adventitious buds
      developed from the meristematic tissue of cotyledonary epicuticula.

PMID- 16944604
TI  - [Molecular phylogenetic relationships of Drosophila immigrans species group based
      on H2a-H2b spacer and Cyt b sequences].
AB  - In order to investigate molecular phylogenetic relationships of Drosophila
      immigrans species group, nucleotide sequences of H2a-H2b spacer regions and
      partial nucleotide sequences of Cytochrome b gene for five specieses subgroup in
      Drosophila immigrans species group and D. hydei which was selected as outgroup
      were acquired. Phylogenetic trees were reconstructed using maximum parsimony,
      maximum likelihood, neighbor joining and Bayesian methods based on H2a-H2b and
      Cyt b DNA sequences. The results indicated that Drosophila curviceps species
      subgroup is located at the base of molecular trees, diverged first in this group;
      the second clade is Drosophila quadrilineata species subgroup; the third is
      Drosophila hypocausta species subgroup; the fourth is Drosophila immigrans
      species subgroup; Drosophila nasuta species subgroup is the last diverged clade.
      Moreover, the phylogentic relationships of seven specieses in Drosophila nasuta
      subgroup was investigated.

PMID- 16944605
TI  - [Cloning and analyzing of the female-specific marker in the dioecious species
      Asparagus officinalis L].
AB  - Sex-linked molecular markers are being obtained, which would be essential to be
      used in the screening of different sex of dioecious plants at the seedling stage.
      Furthermore, it is important in cloning the gene related to the sex. In this
      study the random amplified polymorphic DNA (RAPD) technique was employed with the
      objective to find markers linked to sex determination in Asparagus. A total of
      100 primers were tested with the same PCR cycling procedure. A female-associated
      fragment with a length of about 867bp was generated with S12 primer. The fragment
      was cloned and sequenced, showing it is abundant in AT and contains 2 shorter
      open reading frames. In order to convert the RAPD marker into SCAR (sequence
      characterized amplified regions) marker, 24bp specific primers were constructed
      and used for PCR amplifying. The female-linked dominant SCAR marker was obtained,
      which would be efficient to identify the different sex of Asparagus officinalis
      L.

PMID- 16944606
TI  - [Effects of different cryoprotectants on post-thaw viability of porcine
      preadipocyte].
AB  - To explore the optimal cryoprotectant for porcine preadipocyte cryppreservation,
      the primary pig preadipocytes were cryopreseved with DMSO, ethlyleneglycol(EG),
      PVP and DMSO+PVP cryoprotective agents (CPA) and without CPA, respectively. After
      30d, the cells were recovered, viability of pig preadipocyte cryopreserved with
      different CPAs was evaluated by the Typlan exclusion, growth characteristic was
      analyzed with MTT, the differentiation potentials of pig preadipocytes were
      observed by morphology change from preadipocyte to mature adipocyte and Oil Red O
      staining. The results were as follows: four cryoprotectants all could protect the
      pig preadipocyte from frozen at a certain degree, and the efficiency was as
      follows: PVP > MSO+PVP > DMSO > EG > without cryoprotectant. The growth state and
      the lipogenic capability of the pig preadipocytes cryopreserved with PVP were
      similar to those unfreezing cells. Thus, we draw a conclusion: PVP is the optimal
      cryoprotectant for pig preadipocyte.

PMID- 16944607
TI  - Hypertension in pregnancy.

PMID- 16944608
TI  - Hypertension in pregnancy: hospital based study.
AB  - Eighteen hundred two pregnant women consisting of 750 primigravida and 1,052
      multigravida were screened for hypertension between July 2000 to June 2002.
      Hypertension was noted in 97 (5.38%) patients. Twenty five patients were lost to
      follow up and only 72 patients were included in the final study. The age of the
      patients ranged between 19 to 32 (mean +/- SD = 24.75 +/- 3.36) years. The
      majority of patients 41 (57%) were primigravida and 31 (43%) were multigravida.
      Of 31 multigravida, vast majority (84%) of patients were found to be hypertensive
      in the third trimester. Only 5 (16%) patient had hypertension in the first
      trimester. Stage I, II and III hypertension were noted in 18%, 50% and 32% of
      patients respectively as per JNC-VI criteria. Preeclampsia (PE) was seen in
      44.44% (n=32), eclampsia in 40.28% (n=29), HELLP syndrome in 6.94% (n=5), chronic
      hypertension (HTN) with superimposed PE in 6.94% (n=5) and chronic HTN in 1.38%
      (n=1). Of the 6 patients with chronic hypertension 50% (3) had essential HTN.
      Acute renal failure (S. creat > 3 mg/dl) was seen in 7 patients and 4 required
      dialytic support. Maternal mortality was 5.55% (4) and perinatal death occurred
      in 37.5% (27) of deliveries. Low birth weight was seen in 66.66% (48) of births.
      Hypertension complicated 5.38% of all pregnancies in our study. Preeclampsia
      eclampsia and its variants remain the major cause of hypertension in pregnant
      women. Hypertension during pregnancy is responsible for high fetal mortality and
      low birth weight.

PMID- 16944609
TI  - Prevalence of rheumatic heart disease in school children in Bikaner: an
      echocardiographic study.
AB  - OBJECTIVE: To determine prevalence of rheumatic heart disease (RHD) using
      clinical and echocardiographic criteria and to study influence of socioeconomic
      status (SES) we studied school children in a north-western Indian town. METHODS:
      3292 school children, age range 5-14 years, in two private schools, ten middle
      SES government schools and six low SES government schools were invited to
      participate in the study. 3002 (1837 boys, 1165 girls) were clinically examined
      (response 91%) of which 1042 were in private schools, 1002 in middle SES schools
      and 958 in low SES schools. Prevalence of cardiac murmurs and RHD based on
      clinical diagnosis was determined in school by a trained team of physicians.
      Those with a murmur were further evaluated by Doppler-echocardiography in the
      hospital. Group-specific and age-specific rates (prevalence/thousand) of murmurs
      and cardiac lesions were determined. RESULTS: A significant cardiac murmur was
      observed in 55 subjects (18.3/1000) with similar prevalence in boys (20.7) and
      girls (14.6). The prevalence of murmur was significantly greater in children
      belonging to low SES schools (29.2/1000) as compared to middle SES (18.9) and
      higher SES schools (7.6). RHD prevalence based on clinical diagnosis was observed
      in 50 children (16.7/1000) and was similar in boys (19.1) and girls (12.9).
      Clinical RHD was more in the low SES school children (28.2/1000) as compared to
      middle (17.0) and high SES schools (5.8). RHD was demonstrated on
      echocardiography in 2 children (0.67/1000). Other prevalent cardiac lesions were
      congenital heart disease in 5 (1.66/1000) and mitral valve prolapse in 37
      (12.3/1000). CONCLUSIONS: There is a low prevalence of RHD in school children in
      this region compared to previous Indian studies. Cardiac murmurs are more
      prevalent among low SES children.

PMID- 16944611
TI  - Giant fourth ventricular cyst : diagnostic and therapeutic dilemmas.

PMID- 16944610
TI  - Efficacy of species specific anti-scorpion venom serum (AScVS) against severe,
      serious scorpion stings (Mesobuthus tamulus concanesis Pocock)--an experience
      from rural hospital in western Maharashtra.
AB  - BACKGROUND: Death caused by scorpion envenoming is a common event in the tropical
      and subtropical countries including many regions in India. Severe scorpion
      envenoming causes an autonomic storm producing multi-system organ-failure (MSOF)
      and death. OBJECTIVES: To determine the efficacy of Anti-scorpion venom serum
      (AScVS) in patients stung by scorpions (Mesobuthus tamulus concanesis Pocock-
      earlier called Buthus tamulus); to compare it with other modalities of therapy
      and to detect complications, if any, arising out of AScVS treatment. METHODS:
      Total 48 patients of severe, serious scorpion envenoming syndrome were studied
      during the period from 1992 to 2002. In 17 patients AScVS was the only mode of
      treatment. Others had received adjunctive therapy along with AScVS. RESULTS: 47
      patients out of 48 scorpion sting victims recovered completely. Recovery period
      in patients given AScVS (10 hours) was faster than those who received alpha
      blockers (16-42 hours). No anaphylactic reaction with AScVS was observed.
      CONCLUSIONS: AScVS is effective and safe method of therapy in severe scorpion
      envenoming syndrome.

PMID- 16944612
TI  - Unusual dialysate leakage complicating peritoneal dialysis.

PMID- 16944613
TI  - Tropical infections in the ICU.
AB  - Certain arthropod-borne infections are common in tropical regions because of
      favorable climatic conditions. Water-borne infections like leptospirosis are
      common due to contamination of water especially during the monsoon floods.
      Infections like malaria, leptospirosis, dengue fever and typhus sometimes cause
      life threatening organ dysfunction and have several overlapping features. Most
      patients present with classicial clinical syndromes: fever and thrombocytopenia
      are common in dengue, malaria and leptospirosis; coagulopathy is frequent in
      leptospirosis and viral hepatitis. Hepatorenal syndrome is seen in leptospirosis,
      falciparum malaria and scrub typhus. The pulmonary renal syndrome is caused by
      falciparium malaria, leptospirosis, Hantavirus infection and scrub typhus. Fever
      with altered mental status is produced by bacterial meningitis, Japanese B
      encephalitis, cerebral malarial, typhoid encephalopathy and fulminant hepatic
      failure due to viral hepatitis. Subtle differences in features of the organ
      failure exist among these infections. The diagnosis in some of these diseases is
      made by demonstration of antibodies in serum, and these may be negative in the
      first week of the illness. Hence empiric therapy for more than one disorder may
      be justified in a small proportion of cases. In addition to specific anti
      infective therapy, management of organ dysfunction includes use of mechanical
      ventilation, vasopressor drugs, continuous renal replacement therapy and blood
      products. Timely transfer of these patients to well-equipped ICUs with experience
      in managing these cases can considerably decrease mortality and morbidity.

PMID- 16944614
TI  - Literature search using PubMed: an essential tool for practicing evidence- based
      medicine.
AB  - Efficient literature search is essential to the practice of Evidence-Based
      Medicine. PubMed provides free access to one of the largest searchable biomedical
      databases. Efficient literature search using PubMed requires a good understanding
      of the available search strategies and tools. In this article we present a step
      by-step approach for performing literature search using PubMed. Several PubMed
      tools including 'Single Citation Matcher', 'Clinical Queries', 'Clipboard',
      'Field Tags', and 'Cubby' are highlighted using case based scenarios.

PMID- 16944615
TI  - Biological significance of essential fatty acids.
AB  - Essential fatty acids (EFAs)--linoleic acid (LA) and alpha-linolenic acid (ALA)
      are critical for human survival. EFAs are readily available in the diet. But, to
      derive their full benefit, EFAs need to be metabolized to their respective long
      chain metabolites. EFAs not only form precursors to respective prostaglandins
      (PGs), thromboxanes (TXs), and leukotrienes (LTs), but also give rise to lipoxins
      (LXs), resolvins, isoprostanes, and hydroxy- and hydroperoxyeicosatetraenoates.
      Certain PGs, TXs, and LTs have pro-inflammatory actions whereas LXs and resolvins
      are anti-inflammatory in nature. Furthermore, EFAs and their long-chain
      metabolites modulate the activities of angiotensin converting and HMG-CoA
      reductase enzymes, enhance acetylcholine levels in the brain, increase the
      synthesis of endothelial nitric oxide, augment diuresis, and enhance insulin
      action. Thus, EFAs and their metabolites may function as endogenous ACE and HMG
      CoA reductase inhibitors, nitric oxide enhancers, beta-blockers, diuretics, anti
      hypertensive, and anti-atherosclerotic molecules. In addition, EFAs and their
      long-chain metabolites react with nitric oxide (NO) to yield respective
      nitroalkene derivatives that exert cell-signaling actions via ligation and
      activation of peroxisome proliferator-activated receptors (PPARs). Thus, EFAs and
      their derivatives have varied biological actions that may have relevance to their
      involvement in several physiological and pathological processes.

PMID- 16944616
TI  - Hallerborden Spatz disease.
AB  - Hallervorden Spatz disease is a rare disorder characterized by progressive
      extrapyramidal dysfunction. We report a case of a 18 year old boy who presented
      with cervical dystonia, pigmentary retinal degeneration and MRI brain showing the
      "eye-of-the-tiger" appearance. Renamed recently as "Neurodegeneration with brain
      iron accumulation", we present this case for its rarity and interesting features.

PMID- 16944617
TI  - Christiaan Eijkman (1858-1930). Postal stamps issued on Eijkman by Grenada.
      Christiaan Eijkma--discoverer of cause of Beri-beri.

PMID- 16944618
TI  - Elderly lady with ascites.
AB  - An elderly lady with amylase-rich ascites is presented, whose isoenzyme
      estimation revealed salivary type amylase. Tumour hyperamylasemia is an important
      group among the nonpancreatic causes of elevated amylase.

PMID- 16944619
TI  - Primary amebic meningoencephalitis.
AB  - This case is reported with the intention of highlighting the presentation of
      primary amebic meningoencephalitis as acute meningitis, a rare differential
      diagnosis with presence of free living amoebas in the CSF.

PMID- 16944620
TI  - Familial hypercholesterolemia presenting as intracranial xanthoma.
AB  - A 22 years female who was diagnosed as having cholestseatoma of right ear was
      referred to us for medical fitness. On examination she incidentally had evidence
      of tuberous and tendon xanthomas. She was found to have hypercholesterolemia. On
      mastoid exploration a yellowish groomous mass was seen which was surrounded by
      foamy macrophages, suggestive of 'mastoid xanthoma'. The purpose of this case
      presentation is to report occurrence of such rare case and importance of early
      detection that will warrant treatment with proper diet and medical management.
      This will stabilize lesions and delay complications.

PMID- 16944621
TI  - A rare cause of haematemesis: retrograde jejunogastric intussusception.
AB  - Retrograde Jejunogastric intussusception is a well-recognised, rare but
      potentially fatal, long-term complication of gastro-jejunostomy or Billroth-II
      reconstruction. Only about 200 cases have been reported in literature to date.
      Diagnosis of this condition is difficult in most of the cases. To avoid mortality
      early diagnosis and prompt surgical intervention is mandatory. Since
      gastrojejunostomies with vagotomy are on a declining trend, it is extremely rare
      to come across such a complication. We report such a case that presented with
      haematemesis.

PMID- 16944622
TI  - Malignant colo-jejunal fistula--a rare internal fistula.

PMID- 16944623
TI  - Fenofibrate can increase serum creatinine levels in renal insufficiency.

PMID- 16944624
TI  - Diagnosis of leptospirosis--role of MAT.

PMID- 16944625
TI  - Polymerase chain reaction in the diagnosis of leptospiral infection.

PMID- 16944626
TI  - Pachydermoperiostitis and bisphosphonates.

PMID- 16944627
TI  - Congress fails to preserve right of insurers to be reimbursed.

PMID- 16944628
TI  - Off-label use often presents conundrum for health plans.

PMID- 16944629
TI  - Put away that carrot and stick.

PMID- 16944631
TI  - Finding opportunity where business models meet.

PMID- 16944630
TI  - Return to Jackson Hole? The push for a standard benefit.

PMID- 16944632
TI  - Although employers need depression programs, they may not know it yet.

PMID- 16944633
TI  - Building the paperless health care system. Interview by Patrick Mullen.

PMID- 16944634
TI  - Everyone uses E-mail now (except doctors and patients).

PMID- 16944635
TI  - For Kansas, it's all in the (ID) cards.

PMID- 16944636
TI  - New injectable medication effective against wet AMD.

PMID- 16944637
TI  - Slowdown in premium increase expected to continue into 2007.

PMID- 16944638
TI  - Challenges of climate change: an Arctic perspective.
AB  - Climate change is being experienced particularly intensely in the Arctic. Arctic
      average temperature has risen at almost twice the rate as that of the rest of the
      world in the past few decades. Widespread melting of glaciers and sea ice and
      rising permafrost temperatures present additional evidence of strong Arctic
      warming. These changes in the Arctic provide an early indication of the
      environmental and societal significance of global consequences. The Arctic also
      provides important natural resources to the rest of the world (such as oil, gas,
      and fish) that will be affected by climate change, and the melting of Arctic
      glaciers is one of the factors contributing to sea level rise around the globe.
      An acceleration of these climatic trends is projected to occur during this
      century, due to ongoing increases in concentrations of greenhouse gases in the
      Earth's atmosphere. These Arctic changes will, in turn, impact the planet as a
      whole.

PMID- 16944639
TI  - The Arctic in an earth system context: from brake to accelerator of change.
AB  - Human activities over the past few centuries have profoundly changed the
      functioning of the earth system as a whole. These changes are particularly
      evident in the high latitudes of the Northern Hemisphere, where environmental
      change has been pronounced and rapid. Such changes have implications beyond the
      region, as they can lead to two important feedback processes: the ice-albedo
      feedback and the terrestrial carbon cycle-climate feedback. These processes play
      an exceptionally important role in earth system functioning, particularly because
      they may switch this century from damping the effects of anthropogenic climate
      change to accelerating them. Rapid environmental change in the high latitudes
      also has consequences for issues of direct importance to humans, particularly
      water resources.

PMID- 16944640
TI  - Cumulative effects of climate warming and other human activities on freshwaters
      of Arctic and subarctic North America.
AB  - Despite their generally isolated geographic locations, the freshwaters of the
      north are subjected to a wide spectrum of environmental stressors. High-latitude
      regions are especially sensitive to the effects of recent climatic warming, which
      have already resulted in marked regime shifts in the biological communities of
      many Arctic lakes and ponds. Important drivers of these limnological changes have
      included changes in the amount and duration of snow and ice cover, and, for
      rivers and lakes in their deltas, the frequency and extent of spring floods.
      Other important climate-related shifts include alterations in evaporation and
      precipitation ratios, marked changes in the quality and quantity of lake and
      river water inflows due to accelerated glacier and permafrost melting, and
      declining percentages of precipitation that falls as snow. The depletion of
      stratospheric ozone over the north, together with the clarity of many Arctic
      lakes, renders them especially susceptible to damage from ultraviolet radiation.
      In addition, the long-range atmospheric transport of pollutants, coupled with the
      focusing effects of contaminant transport from biological vectors to some local
      ecosystems (e.g., salmon nursery lakes, ponds draining seabird colonies) and
      biomagnification in long food chains, have led to elevated concentrations of many
      persistent organic pollutants (e.g., insecticides, which have never been used in
      Arctic regions) and other pollutants (e.g., mercury). Rapid development of gas
      and oil pipelines, mining for diamonds and metals, increases in human
      populations, and the development of all-season roads, seaports, and hydroelectric
      dams will stress northern aquatic ecosystems. The cumulative effects of these
      stresses will be far more serious than those caused by changing climate alone.

PMID- 16944641
TI  - Permafrost and changing climate: the Russian perspective.
AB  - The permafrost regions occupy about 25% of the Northern Hemisphere's terrestrial
      surface, and more than 60% of that of Russia. Warming, thawing, and degradation
      of permafrost have been observed in many locations in recent decades and are
      likely to accelerate in the future as a result of climatic change. Changes of
      permafrost have important implications for natural systems, humans, and the
      economy of the northern lands. Results from mathematical modeling indicate that
      by the mid-21st century, near-surface permafrost in the Northern Hemisphere may
      shrink by 15%-30%, leading to complete thawing of the frozen ground in the upper
      few meters, while elsewhere the depth of seasonal thawing may increase on average
      by 15%-25%, and by 50% or more in the northernmost locations. Such changes may
      shift the balance between the uptake and release of carbon in tundra and
      facilitate emission of greenhouse gases from the carbon-rich Arctic wetlands.
      Serious public concerns are associated with the effects that thawing permafrost
      may have on the infrastructure constructed on it. Climate-induced changes of
      permafrost properties are potentially detrimental to almost all structures in
      northern lands, and may render many of them unusable. Degradation of permafrost
      and ground settlement due to thermokarst may lead to dramatic distortions of
      terrain and to changes in hydrology and vegetation, and may lead ultimately to
      transformation of existing landforms. Recent studies indicate that nonclimatic
      factors, such as changes in vegetation and hydrology, may largely govern the
      response of permafrost to global warming. More studies are needed to better
      understand and quantify the effects of multiple factors in the changing northern
      environment.

PMID- 16944642
TI  - Backyard of the rich north: the climate change-related vicious circle of the
      Arctic zone.
AB  - The Arctic zone is full of controversies, unknowns, contrasts, and challenges.
      The following example is enlightening. Saudi Arabia is a country that has been
      considered to have almost unlimited possibilities because of its enormous oil
      earnings. The country has US$60 thousand million purchasing power parity oil
      income each year for its mere 22 million inhabitants. Astonishingly, the Arctic
      zone's income from oil, gas, and minerals is at least as large as that of Saudi
      Arabia, modestly estimated, but the Arctic has less than 4 million people. Most
      money, however, flows away from the tundra, yet social and environmental problems
      remain there. A part of the side effect of consuming these resources-largely
      fossil fuels-returns to the Arctic in the form of greenhouse warming and all its
      consequences. The Arctic zone now warms at approximately double the rate of the
      world average.

PMID- 16944643
TI  - Climate change in the Seychelles: implications for water and coral reefs.
AB  - The Seychelles is a small island state in the western Indian Ocean that is
      vulnerable to the effects of climate change. This vulnerability led the
      Intergovernmental Panel on Climate Change (IPCC) in 2001 to express concern over
      the potential economic and social consequences that may be faced by small island
      states. Small island states should be prepared to adapt to such changes,
      especially in view of their dependence on natural resources, such as water and
      coral reefs, to meet basic human welfare needs. Analysis of long-term data for
      precipitation, air temperature, and sea-surface temperature indicated that
      changes are already observable in the Seychelles. The increase in dry spells that
      resulted in drought conditions in 1999 and the 1998 mass coral bleaching are
      indicative of the events that are likely to occur under future climate change.
      Pre-IPCC Third Assessment Report scenarios and the new SRES scenarios are
      compared for changes in precipitation and air surface temperature for the
      Seychelles. These intercomparisons indicate that the IS92 scenarios project a
      much warmer and wetter climate for the Seychelles than do the SRES scenarios.
      However, a wetter climate does not imply readily available water, but rather
      longer dry spells with more intense precipitation events. These observations will
      likely place enormous pressures on water-resources management in the Seychelles.
      Similarly, sea-surface temperature increases predicted by the HADCM3 model will
      likely trigger repeated coral-bleaching episodes, with possible coral extinctions
      within the Seychelles region by 2040. The cover of many coral reefs around the
      Seychelles have already changed, and the protection of coral-resilient areas is a
      critical adaptive option.

PMID- 16944644
TI  - What determines the current presence or absence of permafrost in the Tornetrask
      region, a sub-arctic landscape in northern Sweden?
AB  - In a warming climate, permafrost is likely to be significantly reduced and
      eventually disappear from the sub-Arctic region. This will affect people at a
      range of scales, from locally by slumping of buildings and roads, to globally as
      melting of permafrost will most likely increase the emissions of the powerful
      greenhouse gas methane, which will further enhance global warming. In order to
      predict future changes in permafrost, it is crucial to understand what determines
      the presence or absence of permafrost under current climate conditions, to assess
      where permafrost is particularly vulnerable to climate change, and to identify
      where changes are already occurring. The Tornetrask region of northern sub-Arctic
      Sweden is one area where changes in permafrost have been recorded and where
      permafrost could be particularly vulnerable to any future climate changes. This
      paper therefore reviews the various physical, biological, and anthropogenic
      parameters that determine the presence or absence of permafrost in the Tornetrask
      region under current climate conditions, so that we can gain an understanding of
      its current vulnerability and potential future responses to climate change. A
      patchy permafrost distribution as found in the Tornetrask region is not random,
      but a consequence of site-specific factors that control the microclimate and
      hence the surface and subsurface temperature. It is also a product of past as
      well as current processes. In sub-Arctic areas such as northern Sweden, it is
      mainly the physical parameters, e.g., topography, soil type, and climate (in
      particular snow depth), that determine permafrost distribution. Even though
      humans have been present in the study area for centuries, their impacts on
      permafrost distribution can more or less be neglected at the catchment level.
      Because ongoing climate warming is projected to continue and lead to an increased
      snow cover, the permafrost in the region will most likely disappear within
      decades, at least at lower elevations.

PMID- 16944645
TI  - Building resilience and adaptation to manage Arctic change.
AB  - Unprecedented global changes caused by human actions challenge society's ability
      to sustain the desirable features of our planet. This requires proactive
      management of change to foster both resilience (sustaining those attributes that
      are important to society in the face of change) and adaptation (developing new
      socioecological configurations that function effectively under new conditions).
      The Arctic may be one of the last remaining opportunities to plan for change in a
      spatially extensive region where many of the ancestral ecological and social
      processes and feedbacks are still intact. If the feasibility of this strategy can
      be demonstrated in the Arctic, our improved understanding of the dynamics of
      change can be applied to regions with greater human modification. Conditions may
      now be ideal to implement policies to manage Arctic change because recent studies
      provide the essential scientific understanding, appropriate international
      institutions are in place, and Arctic nations have the wealth to institute
      necessary changes, if they choose to do so.

PMID- 16944646
TI  - "It's not that simple": A collaborative comparison of sea ice environments, their
      uses, observed changes, and adaptations in Barrow, Alaska, USA, and Clyde River,
      Nunavut, Canada.
AB  - The Arctic environment, including sea ice, is changing. The impacts of these
      changes to Inuit and Inupiat ways of life vary from place to place, yet there are
      common themes as well. The study reported here involved an exchange of hunters,
      Elders, and others from Barrow, Alaska, USA, and Clyde River, Nunavut, Canada, as
      members of a larger research team that also included visiting scientists.
      Although the physical environments of Barrow and Clyde River are strikingly
      different, the uses of the marine environment by residents, including sea ice,
      had many common elements. In both locations, too, extensive changes have been
      observed in recent years, forcing local residents to respond in a variety of
      ways. Although generally in agreement or complementary to one another, scientific
      and indigenous knowledge of sea ice often reflect different perspectives and
      emphases. Making generalizations about impacts and responses is challenging and
      should therefore be approached with caution. Technology provides some potential
      assistance in adapting to changing sea ice, but by itself, it is insufficient and
      can sometimes have undesirable consequences. Reliable knowledge that can be
      applied under changing conditions is essential. Collaborative research and
      firsthand experience are critical to generating such new knowledge.

PMID- 16944647
TI  - How unusual are the "unusual events" detected by control chart techniques in
      healthcare settings?
AB  - Statistical process control (SPC) charts have become widely implemented tools for
      quality monitoring and assurance in healthcare settings across the United States.
      SPC methods have been successfully used in industrial settings to track the
      quality of products manufactured by machines and to detect deviations from
      acceptable Levels of product quality. However, problems may arise when SPC
      methods are used to evaluate human behavior. Specifically, when human behavior is
      tracked over time, the data stream generated usually exhibits periodicity and
      gradualism with respect to behavioral changes over time. These tendencies can be
      quantified and are recognized in the statistical field as autocorrelation. When
      autocorrelation is present, conventional SPC methods too often identify events as
      "unusuaL" when they really should be understood as products of random
      fluctuation. This article discusses the concept of autocorrelation and
      demonstrates the negative impact of autocorrelation on traditional SPC methods,
      with a specific focus on the use of SPC charts to detect unusual events.

PMID- 16944648
TI  - Construct validation of a physician satisfaction survey.
AB  - Hospitals continuously look for ways to improve patient care and retain high
      quality physicians. Previous research indicates that physicians' satisfaction
      with where they practice is a crucial part of addressing these issues. A reliable
      and valid method to assess physician satisfaction is needed in order to identify
      potential areas of discontent. The purpose of the present study was to develop
      and validate a self-administered medical staff satisfaction survey. The survey
      contains 13 Likert-type items divided into three reliable subscales: Quality of
      Patient Care (alpha = .84), Ease of Practice (alpha = .76), and Relationship with
      Leadership (alpha = .92). Results from both exploratory and confirmatory factor
      analyses supported the survey's structure and robustness across three independent
      samples.

PMID- 16944649
TI  - Using quality improvement to enhance research readiness in palliative care.
AB  - Quality improvement is an essential feature of the ongoing development of
      palliative care programs. Little has been written, however, about using quality
      improvement as a strategy to introduce research concepts to staff and
      administrators for the purpose of enhancing research readiness in healthcare
      settings. This article describes such an endeavor. The authors discuss two
      quality improvement initiatives undertaken by a palliative care program in
      Canada. These two examples demonstrate how the quality improvement process acted
      as a catalyst to enhance research readiness.

PMID- 16944650
TI  - Mikel Harry on Six Sigma in healthcare. Interview by Carole S. Guinane.

PMID- 16944651
TI  - How do patients perceive electronic documentation at the bedside?
AB  - Electronic patient records provide an opportunity for real-time access to patient
      information at the bedside, which has the potential to improve healthcare quality
      because it would increase efficiency and facilitate best practice. Patients in
      this study reported that portable computers used at the bedside did not affect
      the clinician-patient relationship. Many patients thought that the technology was
      a valuable tool and that it could foster an efficient hospital atmosphere and
      promote reliable and accurate medical documentation.

PMID- 16944652
TI  - The declining rate of avoidable hospitalizations in the Veterans Health
      Administration.
AB  - Most research shows a lower rate of avoidable hospitalizations associated with
      better access to outpatient care. Such findings have important implications for
      the Veterans Health Administration (VHA), with its change from delivering mainly
      inpatient services to emphasizing quality ambulatory care. From 1999 to 2004 the
      number of avoidable hospitalizations at the VHA increased while the rate per
      10,000 enrollees declined. The trend in the rate of avoidable hospitalizations
      and the rapid growth of the beneficiary population indicate that new enrollees
      had a higher health status and perhaps better access to outpatient care.

PMID- 16944653
TI  - Developing a simpler measure of diabetes care quality.
AB  - The researchers developed a diabetes care quality summary score (DCQSS) that
      weights blood pressure, tobacco use, glucose information, and lipid information
      by cost-effectiveness for improving cardiovascular outcomes. They compared the
      DCQSS to selected Diabetes Quality Improvement Project (DQIP) measures of care in
      an urban Medicaid healthcare maintenance organization population using a
      retrospective chart review. The DCQSS assesses cardiovascular risk compared to
      individual risk-factor control with DQIP measures. The authors believe that the
      DCQSS provides an easier interpretation of diabetes quality than multiple DQIP
      measures.

PMID- 16944654
TI  - Multichannel intraluminal impedance in the evaluation of patients with persistent
      globus on proton pump inhibitor therapy.
AB  - OBJECTIVES: Studies suggest an association between globus sensation ("globus")
      and gastroesophageal reflux. Although globus often persists despite proton pump
      inhibitor (PPI) therapy, the role of nonacid reflux has never been determined.
      Our goal was to use 24-hour multichannel intraluminal impedance (pH/MII) to
      determine 1) reflux characteristics in patients with globus despite PPI therapy;
      2) whether there are differences in reflux patterns between patients with globus
      and patients with heartburn alone; and 3) whether there are differences in the
      number of positive symptom indices when standard pH testing is compared to
      pH/MII. METHODS: Twenty-one adult patients with globus and 12 with heartburn
      symptoms alone underwent 24-hour pH/MII on PPI therapy. Reflux frequencies and
      characteristics were compared in both groups. For patients with globus, the
      symptom index and symptom sensitivity index were calculated. Logistic regression
      was performed to determine which reflux characteristics correlated with symptoms.
      RESULTS: With pH/MII, we detected 1,160 reflux episodes; 64.7% were nonacid, and
      55% reached the proximal sensor. In identifying patients with positive symptom
      indices, pH/MII increased the yield of standard pH testing by 27.8%. Proximal
      reflux was a significant predictor of globus symptoms (p = .04). Nonacid reflux
      approached significance in predicting globus (p = .08). Compared to patients with
      heartburn alone, those with globus had a higher mean frequency of proximal reflux
      (27.76% versus 15.63%; p = .04). CONCLUSIONS: In adults on PPI therapy with
      refractory globus, acid reflux does not predict globus symptoms. Through
      detection of nonacid reflux, pH/MII increased the yield of standard pH testing in
      identifying positive symptom indices. Additionally, pH/MII provided important
      information regarding reflux-symptom correlation. Proximal reflux may be
      predictive of globus symptoms.

PMID- 16944655
TI  - Pulsed angiolytic laser treatment of ectasias and varices in singers.
AB  - OBJECTIVES: Varices and ectasias in singers are typically the result of
      phonotraumatic shearing stresses and/or collision forces on the microcirculation
      within the superficial lamina propria. These lesions can be debilitating in
      performing vocalists because of the effect of recurrent hemorrhage and/or as a
      contributing factor to the morbidity of other mass lesions such as polyps,
      nodules, and cysts. Phonomicrosurgical treatment of performers is understandably
      approached with great trepidation, as the vocal liability of surgically
      disturbing the superficial lamina propria and epithelium must be balanced with
      the inherent detrimental vocal effect(s) of the lesion(s). Pulsed angiolytic
      lasers that emit radiation at high absorbance peaks of oxyhemoglobin were
      examined to determine whether they were an efficacious treatment approach for
      ectasias and varices based on these lasers' mechanisms of action and prior
      experience in phonomicrosurgery. METHODS: A prospective trial was done in 39
      patients (40 procedures in 54 vocal folds) without complication to evaluate the
      effectiveness of a 585-nm pulsed dye laser (PDL; 25 cases) and a 532-nm pulsed
      KTP laser (15 cases) in a noncontact mode to treat 65 varices and 43 ectasias.
      Twenty-nine of 39 patients had varices and ectasias associated with other
      phonotraumatic mass lesions that required resection. RESULTS: All patients have
      resumed full vocal activities, and no patient has had a subsequent hemorrhage or
      vocal deterioration. CONCLUSIONS: Both the 585-nm PDL and the 532-nm pulsed KTP
      laser were found to be efficacious and relatively safe treatment modalities for
      vascular abnormalities of the vocal folds in singers. Noncontact selective
      photoangiolysis of the aberrant vessels prevented future bleeding without
      substantial photothermal trauma to the overlying epithelium and surrounding
      delicate superficial lamina propria, thereby allowing for optimal postoperative
      mucosal pliability and glottal sound production. However, the pulsed KTP laser
      was substantially easier to use because of its enhanced hemostasis due to its
      longer pulse width. Vessel wall rupture was commonplace during use of the 585-nm
      PDL, but rarely occurred during photoangiolysis with the 532-nm pulsed KTP laser.

PMID- 16944656
TI  - Voice-related quality of life in T1 glottic cancer: irradiation versus endoscopic
      excision.
AB  - OBJECTIVES: Several studies have explored posttreatment voice outcomes for early
      glottic cancer with varying results. To further clarify the voice-related quality
      of life (QOL) of T1 glottic cancer patients treated by external beam radiotherapy
      (EBRT) compared to endoscopic carbon dioxide laser excision (CLE), we performed a
      meta-analysis. METHODS: We performed a meta-analysis review for the years 1966 to
      2005 for the Voice Handicap Index (VHI), laryngeal cancer, voice outcome, voice
      quality, and quality of life. Studies in which the VHI was assessed at least 3
      months after treatment for T1 glottic cancer were identified and analyzed by meta
      analysis techniques. RESULTS: Six studies with 208 patients (6 T1b and 202 T1a)
      treated with CLE and 91 patients (6 T1b and 85 T1a) treated with EBRT were
      identified. The posttreatment VHI scores were similar for the EBRT- and CLE
      treated patients (p = .1, Wilcoxon rank sum test). CONCLUSIONS: We conclude that
      CLE and EBRT provide comparable levels of voice handicap for patients with T1
      glottic cancer.

PMID- 16944657
TI  - Prospective study of positional nystagmus in 100 consecutive patients.
AB  - OBJECTIVES: The purpose of this study was to investigate the various diagnoses of
      patients who present with positional nystagmus. METHODS: Positional maneuvers
      were systematically performed in the plane of the posterior canal (PC; Dix
      Hallpike maneuver) and the horizontal canal (HC; patients were rolled to either
      side in a supine position) on 490 consecutive patients essentially referred for
      vertigo and/or gait unsteadiness. RESULTS: One hundred patients (20%) presented
      positional nystagmus. This nystagmus had a peripheral origin in 83 patients,
      including 80 patients with benign paroxysmal positional vertigo (BPPV). In BPPV,
      the PC was involved in 61 patients, the HC in 18 patients (geotropic horizontal
      nystagmus in 11 and ageotropic in 7; changing from geotropic to ageotropic or the
      reverse in 4 patients), and both the PC and HC in 1 patient. There was evidence
      of central positional nystagmus in 12 patients, including positional downbeat
      nystagmus during the Dix-Hallpike maneuver in 7 patients with various neurologic
      disorders, and ageotropic horizontal nystagmus during the HC maneuver in 2
      patients with, respectively, cerebellar ischemia and definite migrainous vertigo.
      The peripheral or central origin of the positional nystagmus could not be
      ascertained in 5 patients, including 1 patient with probable migrainous vertigo
      and another with possible anterior canal BPPV. CONCLUSIONS: A rotatory-upbeat
      nystagmus in the context of PC BPPV, a horizontal nystagmus, whether geotropic or
      ageotropic, due to HC BPPV, and a positional downbeat nystagmus related to
      various central disorders are the 3 most common types of positional nystagmus.
      Geotropic horizontal positional nystagmus and, most certainly, horizontal
      positional nystagmus changing from geotropic to ageotropic or the reverse point
      to HC BPPV. In contrast, an ageotropic horizontal positional nystagmus that is
      not changing (from ageotropic to geotropic) may indicate a central lesion.

PMID- 16944658
TI  - The widely patent cochleovestibular communication of Edward Cock is a distinct
      inner ear malformation: implications for cochlear implantation.
AB  - OBJECTIVES: In 1838, Edward Cock described the anatomic findings in 4 inner ears
      with a widely patent communication between the cochlea and the vestibule that is
      now frequently referred to as the "common cavity deformity" and is often confused
      with Michel's "otocyst deformity." Little is known about the anatomic
      characteristics, including the presence of neural elements in this malformation.
      METHODS: Light microscopy and 2-dimensional and computerized 3-dimensional
      reconstructions were used to determine the histopathology and spiral ganglion
      cell counts in 7 temporal bones with a widely patent cochleovestibular
      communication. RESULTS: In all 7 specimens, the cochlea, vestibule, and
      semicircular canals were distinguishable and a bony defect resulting in an
      abnormal communication of perilymphatic space between the cochlea and vestibule
      was present. The ductus reuniens was abnormally wide in all. The cochlear duct
      varied from less than 1 turn to up to 2 turns. The mean spiral ganglion cells
      were estimated as a percentage of age-matched normal controls at 2.3%, 16.5%, and
      26.8% when the cochlea was approximately 1, 1(1/2), and 2 turns, respectively (p
      = .007). The cribrose area consisted of a thin membrane in 2 specimens, and
      Rosenthal's canal openly communicated with the cerebrospinal fluid space in 3
      specimens. The stapes footplate was abnormal in all 7 specimens and consisted of
      a central defect bridged by a thin membrane in 4 specimens. The facial nerve was
      dehiscent in 5 specimens (71%) and also followed an anomalous course in 2
      specimens (28%). CONCLUSIONS: The widely patent cochleovestibular communication
      is a distinct inner ear malformation, recognition of which may have important
      clinical implications. Estimates of spiral ganglion cells can be predicted from
      the number of cochlear turns. Although cochlear implantation is feasible in
      patients with this malformation, a higher risk of cerebrospinal fluid gushers,
      facial nerve injuries, meningitis, and poor performance would be predicted. A
      better understanding of the anatomy will allow more effective surgical planning
      and techniques and may have a significant impact in improving outcomes.

PMID- 16944659
TI  - Risk of second primary malignancy after radioactive iodine treatment for
      differentiated thyroid carcinoma.
AB  - OBJECTIVES: The association between second primary malignancy (SPM) and
      radioactive iodine (RAI) is controversial. We examined the association between
      RAI and SPM after treatment of differentiated thyroid carcinoma (DTC) using a
      large cohort from a national cancer database. METHODS: From the Surveillance,
      Epidemiology and End Results (SEER) database, all index cases of DTC (papillary
      or follicular) were extracted for the years 1988 to 2001. Two cohorts were
      constructed: 1) patients with DTC who were not treated with RAI, and 2) patients
      with DTC who were treated with RAI. For each cohort, we tabulated all subsequent
      malignancies for each patient, identifying patients in each group with 1 or more
      SPMs. RESULTS: According to inclusion criteria, 18,882 cases of DTC treated
      without RAI (mean follow-up, 55.5 months) and 10,349 cases treated with RAI (mean
      follow-up, 61.8 months) were identified. The most common SPM sites were breast or
      prostate followed by colon or lung for both groups. On univariate analysis, SPMs
      developed in 6.7% of patients without RAI versus 4.8% of those with RAI (p <
      .001, univariate chi-squared). However, on multivariate analysis, only age and
      male gender had statistically significant hazard ratios (1.052 and 1.438,
      respectively; p < .001); follicular carcinoma histology and use of RAI did not
      influence occurrence of SPM after DTC (p = .180 and p = .789, respectively).
      CONCLUSIONS: Use of RAI does not elevate the risk of SPM. Concern about SPM
      induction should not adversely affect the decision to administer RAI for DTC.

PMID- 16944660
TI  - Subglottic wound healing in a new rabbit model of acquired subglottic stenosis.
AB  - OBJECTIVES: It is difficult to develop models of subglottic stenosis in small
      animals that ensure reliable stenosis. We therefore sought to establish a new
      animal model of subglottic stenosis in rabbits and observe subglottic wound
      healing. METHODS: Using a diode laser under endoscopic visualization after
      anterior tracheal incision, we induced full-thickness injury to the subglottis in
      60 rabbits: 20 on the anterior 120 degrees, 20 on the posterior 120 degrees, and
      20 circumferentially. The animals were painlessly sacrificed 2 or 4 weeks later,
      and their gross and histologic findings were compared with those of each other
      and with those of 16 age-matched nonwounded controls. RESULTS: Of the 60 animals,
      22 died, primarily of acute airway obstruction and mostly in the circumferential
      group. All of the injured rabbits showed subglottic stenosis compared with
      controls, ranging from 12% to 56% reduction in cross-sectional area in the 120
      degrees injured groups and from 32% to 82% reduction in the 360 degrees injured
      group. The significant narrowing of the subglottic lumina resulted in substantial
      early mortality in the circumferential group. Histologic examination showed
      mucosal ulceration, inflammation, and formation of granulation tissues during the
      acute phase after wounding, and collapse of the injured cartilage and submucosal
      thickening and fibrosis at later times. CONCLUSIONS: Subglottic healing and
      stenosis depend on the extent of cartilaginous injury. This model may be useful
      for developing methods to treat subglottic stenosis.

PMID- 16944661
TI  - Effects of tumor necrosis factor alpha antagonist, platelet activating factor
      antagonist, and nitric oxide synthase inhibitor on experimental otitis media with
      effusion.
AB  - OBJECTIVES: We studied the inflammatory responses in otitis media with effusion
      induced by lipopolysaccharide (LPS) in rats, and compared the preventive effects
      of tumor necrosis factor (TNF) soluble receptor type I (sTNFRI, a TNF-alpha
      antagonist), platelet activating factor antagonist, and the nitric oxide synthase
      inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). METHODS: We used 2 control
      groups of Sprague Dawley rats (untreated and saline-treated) and 4 experimental
      groups, which all received an intratympanic injection of LPS, followed in 3
      groups by experimental treatment of the same ear. The LPS group had no additional
      treatment. The L-NAME group received intraperitoneal injection of L-NAME and was
      reinjected after 12 hours. The A-85783 group was first given an intraperitoneal
      injection of A-85783. The sTNFRI group was first given an intratympanic injection
      of sTNFRI. Twenty-four hours after the initial intratympanic injection of LPS,
      temporal bones from each group were examined histopathologically and the vascular
      permeability of the middle ear mucosa was measured by Evans blue vital dye
      staining. RESULTS: The L-NAME, A-85783, and sTNFRI groups showed significantly
      reduced capillary permeability, subepithelial edema, and infiltration of
      inflammatory cells in comparison with the LPS group. There were no differences in
      capillary permeability, subepithelial edema, or infiltration of inflammatory
      cells between the A-85783 and sTNFRI groups. The L-NAME group showed no
      difference in vascular permeability or subepithelial edema in comparison with the
      A-85783 and sTNFRI groups, but showed more infiltration of inflammatory cells.
      CONCLUSIONS: We conclude that sTNFRI, A-85783, and L-NAME can be proposed as
      alternative future treatments for otitis media with effusion. However, L-NAME may
      be the least effective of these agents.

PMID- 16944662
TI  - Submucosal minimally invasive lingual excision: an effective, novel surgery for
      pediatric tongue base reduction.
AB  - OBJECTIVES: The aim of this study was to develop an effective single intraoral,
      minimally invasive technique to reduce the enlarged tongue base in children with
      obstructive macroglossia. METHODS: We present the anatomic dissection of fresh
      cadavers and a representative case series of children who underwent submucosal
      minimally invasive lingual excision (SMILE) with a plasma-mediated radiofrequency
      device (coblation) under intraoral ultrasonic and endoscopic guidance. Multiple
      anatomic dissections determined the relative location of the hypoglossal nerve
      and lingual neurovascular bundle in relation to removable tongue base
      musculature. A pediatric case series demonstrates the straightforward SMILE
      technique. RESULTS: Laboratory anatomic dissection and clinical lingual
      ultrasonography revealed the surgical safety borders for SMILE. The surgical
      safety and efficacy of SMILE is demonstrated by preoperative and postoperative
      clinical examinations and polysomnograms in children with obstructive
      macroglossia (such as Beckwith-Wiedemann and Down syndromes and tongue vascular
      malformation). Coblation submucosally removes excessive tongue base tissue
      through a small anterior tongue incision. SMILE was performed without excessive
      pain, bleeding, edema, infection, or tongue dysfunction. CONCLUSIONS: SMILE is an
      effective novel operation that incorporates coblation with ultrasonography and
      endoscopic guidance for children who need tongue base reduction. Anatomic
      dissection and clinical cases demonstrate the potential for aggressive yet
      relatively safe tissue removal by this minimally invasive technique. SMILE also
      has significant potential for adults with obstructive sleep apnea due to a large
      tongue base.

PMID- 16944663
TI  - Peripheral facial nerve regeneration using collagen conduit entubulation in a cat
      model.
AB  - OBJECTIVES: Facial nerve (FN) injuries are functionally, psychologically, and
      financially debilitating. Facial nerve autograft repairs produce significant
      donor nerve morbidity and functional results that rarely exceed House-Brackmann
      (HB) grade III over VI. In this study we sought to enhance FN regeneration via
      collagen conduit entubulation. METHODS: Five control cats underwent right ("cut
      side") FN transection and immediate microsurgical anastomosis repair. Five
      experimental cats underwent identical repairs plus collagen conduit entubulation
      of each anastomosis. RESULTS: Postoperative behavioral observations revealed
      gradual FN functional recovery in all cats, who attained adapted HB grades of II
      to III over VI after 6 weeks. Electromyographic latencies and amplitudes from the
      bilateral orbicularis oculi and orbicularis oris muscles indicated restoration of
      FN continuity in all 10 cats. In comparison with FN repairs without conduits,
      repairs with conduits significantly enhanced recovery of amplitude in cut-side
      orbicularis oculi muscles (p = .037) and latency in cut-side orbicularis oris
      muscles (p = .048). In comparison with intact left ("uncut-side") FN latencies
      and amplitudes, more statistically significant differences in cut-side FN
      function were observed in repairs without conduits than in repairs with conduits.
      Conduits therefore facilitated a more complete return of electrophysiological
      function. Histologic analyses confirmed FN continuity and revealed more organized
      FN regenerative architecture in conduit-implanted repairs. CONCLUSIONS: The
      overall results support enhanced FN regeneration with collagen conduit
      entubulation.

PMID- 16944665
TI  - California IPA outruns the market as capitation rebounds.

PMID- 16944664
TI  - Generics lead moderating drug trend, but price spike looms.

PMID- 16944666
TI  - Benchmarks show physicians losing ground in real income.

PMID- 16944667
TI  - Genetically increased risk of sleep disruption in Alzheimer's disease.
AB  - STUDY OBJECTIVES: To investigate the role of a monoamine A oxidase promoter
      polymorphism in sleep disruption in Alzheimer's disease (AD). DESIGN: A case
      control association analysis. SETTING: Sleep disturbance in AD is common, is
      extremely stressful for caregivers, and increases the risk of
      institutionalisation. It remains unclear why only some patients develop sleep
      disturbance; neuropathologic changes of AD are not typically seen in the areas of
      the brain responsible for sleep. We hypothesized that the risk of sleep
      disturbance is, at least in part, influenced by the availability of serotonin
      used for melatonin synthesis secondary to polymorphic variation at the enzyme
      monoamine oxidase A (MAO-A). PATIENTS: Patients with AD diagnosed according to
      standard criteria. INTERVENTIONS: Data were collected using the Sleep domain of
      the Neuropsychiatric Inventory with Caregiver Distress. Patients' cognition and
      function were assessed using the Mini-Mental State Examination and the Functional
      Assessment Staging. Genotyping of apolipoprotein E (APOE) and of the 30 bp
      variable number tandem repeat of the MAO-A promoter was by standard methods.
      MEASUREMENTS AND RESULTS: Of 426 patients surveyed, 54% experienced sleep
      disturbance. We found that the high-activity 4-repeat allele of the MAO-A VNTR
      promoter polymorphism confers increased susceptibility to sleep disturbance (p =
      .008). A quantitative sleep disturbance score was significantly higher in the
      patients possessing MAO-A 4-repeat allele genotypes. APOE had no influence on the
      development of an altered sleep phenotype. CONCLUSIONS: We conclude that sleep
      disturbance in AD is common and distressing and is associated with genetic
      variation at MAO-A.

PMID- 16944668
TI  - Association of usual sleep duration with hypertension: the Sleep Heart Health
      Study.
AB  - STUDY OBJECTIVES: Limited experimental data suggest that sleep restriction
      acutely elevates blood pressure; however, little is known about the relationship
      between usual sleep duration and hypertension. This study assesses the
      relationship between usual sleep duration and hypertension in a community-based
      cohort. DESIGN: Cross-sectional observational study. SETTING: The Sleep Heart
      Health Study, a community-based prospective study of the cardiovascular
      consequences of sleep-disordered breathing. PARTICIPANTS: Two thousand eight
      hundred thirteen men and 3097 women, aged 40 to 100 years. INTERVENTIONS: None.
      MEASUREMENTS AND RESULTS: Usual weekday and weekend sleep durations were obtained
      by questionnaire, and their weighted average were categorized as less than 6, 6
      to less than 7, 7 to less than 8, 8 to less than 9, and 9 or more hours per
      night. Hypertension was defined as a systolic blood pressure of 140 mm Hg or
      greater, a diastolic blood pressure of 90 mm Hg or greater, or use of medication
      to treat hypertension. The relationship between sleep duration and hypertension
      was examined using categorical logistic regression with adjustment for age, sex,
      race, apnea-hypopnea index, and body mass index. Compared to subjects sleeping 7
      to less than 8 hours per night, those sleeping less than 6 and between 6 and 7
      hours per night had adjusted odds ratios for hypertension of 1.66 (95% confidence
      interval 1.35-2.04) and 1.19 (1.02-1.39), respectively, whereas those sleeping
      between 8 and 9 and 9 or more hours per night had adjusted odds ratios for
      hypertension of 1.19 (1.04-1.37) and 1.30 (1.04-1.62), respectively (p < .0001
      for association of sleep duration with hypertension). These associations
      persisted when analyses were further adjusted for caffeine and alcohol
      consumption, current smoking, insomnia symptoms, depression symptoms, sleep
      efficiency, and prevalent diabetes mellitus or cardiovascular disease.
      CONCLUSIONS: Usual sleep duration above or below the median of 7 to less than 8
      hours per night is associated with an increased prevalence of hypertension,
      particularly at the extreme of less than 6 hours per night.

PMID- 16944669
TI  - CSF versus serum leptin in narcolepsy: is there an effect of hypocretin
      deficiency?
AB  - STUDY OBJECTIVE: To determine if hypocretin deficiency is associated with
      abnormally low serum leptin levels, a putative cause of increased body mass index
      in narcoleptics. DESIGN: Cross-sectional controlled study. PARTICIPANTS: Three
      hundred seventy subjects, including 111 healthy controls, 93 narcoleptic subjects
      with hypocretin deficiency (cerebrospinal fluid [CSF] hypocretin-1 levels < 110
      pg/mL), 72 narcoleptic subjects with normal hypocretin levels, and 89 subjects
      with other sleep disorders INTERVENTION: After completing the Stanford Sleepiness
      Inventory, participants underwent spinal taps and blood sampling for measurement
      of CSF leptin and hypocretin-1 levels, HLA DQB1*0602 phenotyping, and serum
      leptin and C-reactive protein levels. RESULTS: Serum leptin levels were similar
      in narcoleptic subjects, whether hypocretin-deficient (13.2 +/- 1.7 ng/mL, mean
      +/- SEM) or not (13.0 +/- 1.8 ng/mL), controls (10.1 +/- 1.1 ng/mL) and subjects
      with other sleep disorders (11.5 +/- 1.6 ng/mL). Similarly, the CSF leptin levels
      and the CSF: serum leptin ratios (an indicator of brain leptin uptake) were not
      different between groups. Serum and CSF leptin levels were higher in women and in
      subjects with higher body mass indexes. Leptin brain uptake decreased in women,
      in the aged, and in more-obese subjects. In contrast with a presumed inhibitory
      effect of leptin on hypocretin-containing cells, CSF leptin levels tended to
      correlate positively with CSF hypocretin-1 levels. C-reactive protein was higher
      (4.2 +/- 0.9 mg/L) in narcoleptic subjects with hypocretin deficiency than in
      controls (1.4 +/- 0.3 mg/L, p = .0055), a difference still significant after
      adjustment on confounding factors. DISCUSSION: Our data do not support a role for
      leptin in mediating increased body mass index in narcolepsy. A moderate but
      selective increase in C-reactive protein in hypocretin-1 deficient subjects
      should prompt research on inflammation in narcolepsy.

PMID- 16944670
TI  - Off-label treatment of severe childhood narcolepsy-cataplexy with sodium oxybate.
AB  - STUDY OBJECTIVES: To evaluate the efficacy and side-effect profile of off-label
      sodium oxybate (gamma hydroxy butyrate) therapy in severe childhood narcolepsy
      cataplexy. DESIGN: Retrospective; chart review. SETTING: A multidisciplinary
      tertiary sleep center. PATIENTS: A group of eight children with severe narcolepsy
      cataplexy diagnosed on the basis of clinical history, nocturnal polysomnography
      and the multiple sleep latency test were studied. A modified Epworth Sleepiness
      Scale and an arbitrary cataplexy severity scale (1 = minimal weakness, 2 =
      voluntarily preventable falls, 3 = falls to the ground) were utilized.
      INTERVENTIONS: Sodium oxybate therapy; concurrent medications were maintained.
      MEASUREMENTS AND RESULTS: Before sodium oxybate therapy, all subjects had
      suboptimally controlled sleepiness and cataplexy. Following treatment with sodium
      oxybate, 7/8 subjects (88%) improved. Cataplexy frequency decreased from a median
      of 38.5 to 4.5/ week (p = 0.0078). Cataplexy severity decreased from 2.75 to 1.75
      (p = 0.06). The Epworth Sleepiness Scores improved from a median of 19 to 12.5 (p
      = 0.02). Suicidal ideation, dissociative episodes, tremor and constipation
      occurred in one subject each and terminal insomnia in two. Three of the 8 (38%)
      discontinued therapy. Two stopped the drug owing to side effects and one due to
      problems with postal delivery of the medication. CONCLUSIONS: This is the first
      report on sodium oxybate therapy in childhood narcolepsy-cataplexy. Our finding
      of improvement in cataplexy and sleepiness suggests that this medication is
      effective in treating severe childhood narcolepsy-cataplexy.

PMID- 16944671
TI  - Practice parameters for the medical therapy of obstructive sleep apnea.
AB  - Therapies for obstructive sleep apnea other than positive airway pressure, oral
      appliances, and surgical modifications of the upper airway are reviewed in this
      practice parameter. Several of these therapies such as weight loss and positional
      therapy hold some promise. Others, such as serotonergic agents, may gain
      credibility in the future but lack well-designed clinical trials. No practice
      parameters could be developed for a number of possible therapeutic modalities
      that had little or no evidence-based data on which to form a conclusion. The role
      of an organized, targeted weight-loss program either as a single therapy or as a
      supplement to PAP needs to be clarified. Although bariatric surgery is
      increasingly performed for refractory medically complicated obesity, its long
      term effectiveness in treatment of obstructive sleep apnea in morbidly obese
      patients is not yet demonstrated. Positional therapy, or methods for preventing
      sleep in the supine position, has probably been underutilized due to lack of
      easily measured predictive factors and randomized controlled trials.

PMID- 16944672
TI  - Medical therapy for obstructive sleep apnea: a review by the Medical Therapy for
      Obstructive Sleep Apnea Task Force of the Standards of Practice Committee of the
      American Academy of Sleep Medicine.
AB  - A significant number of patients with obstructive sleep apnea neither tolerate
      positive airway pressure (PAP) therapy nor achieve successful outcomes from
      either upper airway surgeries or use of an oral appliance. The purpose of this
      paper, therefore, was to systematically evaluate available peer-reviewed data on
      the effectiveness of adjunctive medical therapies and summarize findings from
      these studies. A review from 1985 to 2005 of the English literature reveals
      several practical findings. Weight loss has additional health benefits and should
      be routinely recommended to most overweight patients. Presently, there are no
      widely effective pharmacotherapies for individuals with sleep apnea, with the
      important exceptions of individuals with hypothyroidism or with acromegaly.
      Treating the underlying medical condition can have pronounced effects on the
      apnea/hypopnea index. Stimulant therapy leads to a small but statistically
      significant improvement in objective sleepiness. Nonetheless, residual sleepiness
      remains a significant health concern. Supplemental oxygen and positional therapy
      may benefit subsets of patients, but whether these therapies reduce morbidities
      as PAP therapy does will require rigorous randomized trials. PAP therapy has set
      the bar high for successful treatment of sleep apnea and its associated
      morbidities. Nonetheless, we should strive towards the development of universally
      effective pharmacotherapies for sleep apnea. To accomplish this, we require a
      greater knowledge of the neurochemical mechanisms underlying sleep apnea, and we
      must use this infrastructure of knowledge to design well-controlled, adequately
      powered studies that examine, not only effects on the apnea/hypopnea index, but
      also the effects of pharmacotherapies on all health related outcomes shown
      beneficial with PAP therapy.

PMID- 16944673
TI  - Lateral sleeping position reduces severity of central sleep apnea / Cheyne-Stokes
      respiration.
AB  - INTRODUCTION: The influence of sleeping position on obstructive sleep apnea
      severity is well established. However, in central sleep apnea with Cheyne Stokes
      respiration (CSA-CSR) in which respiratory-control instability plays a major
      pathophysiologic role, the effect of position is less clear. STUDY OBJECTIVES: To
      examine the influence of position on CSA-CSR severity as well as central and
      mixed apnea frequency. METHODS: Polysomnograms with digitized video surveillance
      of 20 consecutive patients with heart failure and CSA-CSR were analyzed for total
      apnea-hypopnea index, mean event duration, and mean oxygen desaturation according
      to sleep stage and position. Position effects on mixed and central apnea index,
      mean apnea duration, and mean desaturation were also examined in non-rapid eye
      movement sleep. RESULTS: Data are presented as mean +/- SEM unless otherwise
      indicated. Group age was 59.9 +/- 2.3 years, and total apnea-hypopnea index was
      26.4 +/- 3.0 events per hour. Compared with supine position, lateral position
      reduced the apnea-hypopnea index in all sleep stages (Stage 1, 54.7 +/- 4.2
      events per hour vs 27.2 +/- 4.1 events per hour [p < .001]; Stage 2, 43.3 +/- 6.1
      events per hour vs 14.4 +/- 3.6 events per hour [p < .001]; slow-wave sleep, 15.9
      +/- 6.4 events per hour vs 5.4 +/- 2.9 events per hour [p < .01]; rapid eye
      movement sleep, 38.0 +/- 7.3 events per hour vs 11.0 +/- 3.0 events per hour [p <
      .001]). Lateral position attenuated apnea and hypopnea associated desaturation
      (supine 4.7% +/- 0.3%, lateral 3.0% +/- 0.4%; p < .001) with no difference in
      event duration (supine 25.7 +/- 2.8 seconds, lateral 26.9 +/- 3.4 seconds; p =
      .921). Mixed apneas were longer than central (29.1 +/- 2.1 seconds and 19.3 +/-
      1.1 seconds; p < .001) and produced greater desaturation (6.1% +/- 0.5% and 4.5%
      +/- 0.5%, p = .003). Lateral position decreased desaturation independent of apnea
      type (supine 5.4% +/- 0.5%, lateral 3.9% < or = 0.4%; p = .003). CONCLUSIONS:
      Lateral position attenuates severity of CSA-CSR. This effect is independent of
      postural effects on the upper airway and is likely to be due to changes in
      pulmonary oxygen stores. Further studies are required to investigate mechanisms
      involved.

PMID- 16944674
TI  - Effect of zolpidem on the efficacy of continuous positive airway pressure as
      treatment for obstructive sleep apnea.
AB  - STUDY OBJECTIVE: Assess the effect of the hypnotic zolpidem on the efficacy of
      nasal continuous positive airway pressure for treatment of Obstructive Sleep
      Apnea. DESIGN: Randomized double blind placebo controlled, cross-over study.
      SETTING: Veterans Administration Medical Center. PATIENTS: 16 patients with
      severe obstructive sleep apnea (apnea+ hypopnea index > 30/hr), on CPAP therapy
      for at least 6 months. INTERVENTION: Three sleep studies were performed over
      three consecutive weeks. On night one the pressure level required to prevent
      apnea, hypopnea, and snoring was determined. On the second and third study
      nights, either placebo (P) or 10 mg of zolpidem (Z) was given (random order) and
      subjects slept on the CPAP level determined on the first night. MEASUREMENTS:
      Sleep architecture, apnea + hypopnea index, arterial oxygen saturation. RESULTS:
      The sleep architecture was similar on the placebo and zolpidem nights except for
      a decrease in the sleep latency ( P: 23.5 +/- 4.7; Z: 13.1 +/- 3.3 minutes, P <
      0.02) and a small decrease in the arousal index (P < 0.03) on zolpidem nights.
      The was no significant difference between placebo and zolpidem nights in the
      apnea + hypopnea index (P: 4.8 +/- 1.4 versus Z : 2.7 +/- 0.47 events/hour),
      oxygen desaturation index (1.46 +/- 0.53 versus 0.81 +/- 0.29
      desaturations/hour), or the lowest SaO2 (91.4 +/- 0.6 versus 91.0 +/- 0.7%).
      CONCLUSIONS: Acute administration of zolpidem 10 mg does not impair the efficacy
      of an effective level of CPAP in patients with severe obstructive sleep apnea.

PMID- 16944675
TI  - Family conflict in childhood: a predictor of later insomnia.
AB  - STUDY OBJECTIVES: To examine the association between childhood exposure to family
      conflict and insomnia at 18 years of age. DESIGN: Longitudinal prospective data
      on an entire birth cohort were obtained. Parents completed the Conflict subscale
      of the Moos Family Environment Scale when the study members were 7, 9, 13, and 15
      years of age. Insomnia was examined in a standardized interview when the
      participants were aged 18 years. SETTING: Participants were born in Dunedin, New
      Zealand, and were interviewed at this location. PATIENTS OR PARTICIPANTS: One
      thousand thirty-seven children born between April 1, 1972, and March 31, 1973,
      enrolled in the study (52% male). At age 18 years, 993 (97% of living cohort
      members) provided data. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The mean
      level of family conflict at age 7 to 15 years predicted insomnia at 18 years
      after controlling for sex, socioeconomic status, sleep problems at 9 years, and
      self-reported health (odds ratio [95% confidence interval] = 1.42 [1.17-1.73], p
      < .001). There was a dose-response relationship, whereby the more assessments at
      which families scored in the top 25% for conflict, the greater the young person's
      likelihood of developing insomnia at age 18 years. This association was present
      even after controlling for depression at 18 years. CONCLUSIONS: This study
      demonstrates a modest but robust longitudinal link between family conflict during
      childhood and insomnia experienced at 18 years of age. Future work needs to
      replicate this finding in different populations and to elucidate the mechanisms
      underlying this association.

PMID- 16944677
TI  - Circadian phase in delayed sleep phase syndrome: predictors and temporal
      stability across multiple assessments.
AB  - STUDY OBJECTIVES: To assess temporal stability across multiple assessments and
      predictors of circadian phase in participants with delayed sleep phase syndrome
      (DSPS), relative to normal-sleeping matched controls. DESIGN: Circadian phase was
      assessed by salivary dim light melatonin onset (DLMO) during 3 laboratory visits,
      separated by at least 5 days--2 scheduled at the end of the week (Friday) and 1
      scheduled at the end of the weekend (Sunday). PATIENTS: Eight young volunteers
      who met International Classification of Sleep Disorders-Revised criteria for
      DSPS, and 8 age- and sex-matched controls (age range 19-27 years old).
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: As expected, salivary DLMO occurred
      significantly later in patients with DSPS than in controls (F 10.561, p = .006).
      However, circadian phase did not change significantly across the 3 DLMO
      assessments in either group. Estimations of circadian phase were not
      significantly different in the assessments conducted on weekdays versus weekends.
      Predictors of circadian phase included time of morning light exposure (R2 =
      0.777; p < .001), recent wake time (R2 = 0.701, p < .001), and self-reported
      chronotype (R2 = 0.320, p = .016). DLMO preceded wake time in both groups by
      approximately 10.75 hours. CONCLUSIONS: Across serial laboratory assessments on
      an ad lib sleep schedule, patients with DSPS appeared more similar to than
      different from normal-sleeping control subjects, except for a stable delay in
      circadian phase.

PMID- 16944676
TI  - Impaired sleep-related memory consolidation in primary insomnia--a pilot study.
AB  - STUDY OBJECTIVES: To compare sleep-related consolidation of procedural memory in
      patients with primary insomnia and healthy controls. DESIGN: Controlled
      comparison pilot study. SETTING: Sleep Laboratory of the Department of Psychiatry
      and Psychotherapy, University of Freiburg, Germany. PATIENTS OR PARTICIPANTS:
      Seven patients with primary insomnia and 7 sex-, age-, and IQ-matched healthy
      controls. INTERVENTIONS: Subjects spent 1 night in the sleep laboratory with
      polysomnographic monitoring. Performance on a mirror tracing task was measured
      before and after sleep. MEASUREMENTS AND RESULTS: Polysomnography revealed a
      trend toward disturbed sleep in the patients, compared with the control group,
      without reaching significance. Performance in the mirror tracing task before
      sleep did not differ between the groups. Both groups performed significantly
      better in the retest condition after sleep. Healthy controls showed an
      improvement of 42.8% +/- 5.8% in the mirror tracing draw time, whereas patients
      with insomnia showed an improvement of 20.4% +/- 14.8% (multivariate analyses of
      variance test session x group interaction: F(3,10) = 10.9, p = .002).
      CONCLUSIONS: These preliminary findings support the view that sleep-associated
      consolidation of procedural memories may be impaired in patients with primary
      insomnia.

PMID- 16944678
TI  - Validation of a new noninvasive method to measure blood pressure and assess
      baroreflex sensitivity in preterm infants during sleep.
AB  - STUDY OBJECTIVES: Accuracy and precision of a noninvasive device for continuously
      measuring blood pressure (BP) (Finometer, FMS, The Netherlands) during sleep was
      assessed in preterm infants. DESIGN: Absolute BP beat-to-beat values, interbeat
      changes, measurement precision, and baroreflex sensitivity were compared with BP
      measurements from intraarterial catheters. PARTICIPANTS: Ten preterm infants
      (gestational age 27-36 weeks; birth weight 964-2620 gm) were studied in the
      neonatal intensive care unit. MEASUREMENTS AND RESULTS: The 2 modes of BP
      measurement were compared in 2-minute epochs (n = 10-12/infant). Mean arterial
      pressure, systolic arterial pressure, and diastolic arterial pressure were
      analyzed beat to beat, and baroreflex sensitivity was assessed using spontaneous
      sequence analysis. Mean differences for absolute BP (mm Hg) were as follows: mean
      arterial pressure, 3 (limits of agreement, -1 to 8); systolic arterial pressure, 
      4 (-8 to 1); and diastolic arterial pressure, 7 (4 to 10). Mean differences and
      limits of agreement for interbeat changes were essentially 0 for mean arterial
      pressure, systolic arterial pressure, and diastolic arterial pressure. Precision
      (+/- 95% confidence intervals, mm Hg) for the Finometer were mean arterial
      pressure +/- 7, systolic arterial pressure +/- 8, and diastolic arterial pressure
      +/- 6. Precision was greater for the arterial catheter (mean arterial pressure +/
      3, systolic arterial pressure +/- 4, and diastolic arterial pressure +/- 4).
      Baroreflex sensitivity calculated from the Finometer BP was (mean +/- SEM, ms/mm
      Hg) 1.74 +/- 0.23 and, from the catheter system, BP was 1.56 +/- 0.21 (p value
      NS). CONCLUSIONS: The Finometer provides accurate measurements of beat-to-beat BP
      and baroreflex sensitivity. The ability to continuously measure BP and baroreflex
      sensitivity during sleep in infants may provide vital clues into pathologic
      conditions associated with impaired autonomic control during sleep.

PMID- 16944679
TI  - Episodic diencephalic hypoperfusion in Kleine-Levin syndrome.
AB  - A 22 year-old woman suffered from recurrent episodes of hypersomnia, apathy, and
      hyperphagia. The symptoms occurred 3 to 4 times per year, and each attack lasted
      2 to 3 weeks. 99mTc-ethylcysteinate dimer brain single photon emission computed
      tomography (SPECT) was performed during symptomatic and asymptomatic periods. To
      localize brain regions with perfusion changes during symptomatic period,
      asymptomatic SPECT was subtracted from symptomatic SPECT. The subtracted SPECT
      showed significant hypoperfusion in the left hypothalamus, bilateral thalami,
      basal ganglia, bilateral medial and dorsolateral frontal regions, and left
      temporal lobe during the symptomatic period. These cerebral hypoperfusion areas
      support the diencephalic hypothesis and clinical symptoms of Kleine-Levin
      syndrome.

PMID- 16944680
TI  - Management of radial scars found at percutaneous breast biopsy.
AB  - OBJECTIVE: To determine whether percutaneous biopsy can safely differentiate
      radial scars (RS) that can be followed from those that require excision. METHODS:
      Retrospective analysis of prospectively collected data regarding 15 986 biopsies
      was performed at the Centre Hospitalier de l'Universite de Montreal between
      October 1995 and December 2003 and yielded 227 RS. The type of biopsy, number of
      cores, and mammographic characteristics were recorded. Only lesions with surgical
      pathology or 24 months of mammographic stability were considered for analysis.
      Subgroup analyses were performed for patients who underwent 14-gauge core biopsy
      (CB), 11-gauge vacuum-assisted biopsy (VAB), or both. RESULTS: Among the 14-gauge
      CBs (n = 176), data were available for 144 (81.8%); among the 11-gauge VABs (n =
      51), data were available for 40 (78.4%). Thirty lesions had 14-gauge CB followed
      by 11-gauge VAB. RS were associated with cancer in 19.6%, with a high-risk lesion
      in 20.1% and a benign lesion in 60.3%. Overall, 4% of cancers were missed (5% for
      14-gauge CB and 0% for 11-gauge VAB), and cancer was underestimated in 22.2% (25%
      for 14-gauge CB and 16.7% for 11-gauge VAB). One (3.7%) additional cancer was
      found when benign radial scar on 14-gauge CB underwent subsequent 11-gauge VAB.
      Cancer was associated with 37% of RS presenting as masses but with only 17.1% of
      distortions and 12.3% of microcalcifications. CONCLUSIONS: If benign radial scar
      is found on 14-gauge CB, further evaluation is needed with 11-gauge VAB or
      surgery. Our data support mammographic follow-up for RS that are benign on 11
      gauge VAB.

PMID- 16944681
TI  - Radiation doses to patients receiving computed tomography examinations in British
      Columbia.
AB  - OBJECTIVE: To estimate the diagnostic reference levels and effective radiation
      dose to patients from routine computed tomography (CT) examinations in the
      province of British Columbia, Canada. METHODS: The patient weight, height and
      computed tomography dose index or dose linear product (DLP) were recorded on
      study sheets for 1070 patients who were referred for clinically indicated routine
      CT examinations at 18 radiology departments in British Columbia. Sixteen of the
      scanners were multidetector row scanners. RESULTS: The average patient dose
      varied from hospital to hospital. The largest range was found for CT of the
      abdomen, for which the dose varied from 3.6 to 26.5 (average 10.1) mSv. For head
      CT, the range was 1.7 to 4.9 (average 2.8) mSv; for chest CT, it was 3.8 to 26
      (average 9.3) mSv; for pelvis CT, it was 3.5 to 15.5 (average 9.0) mSv; and for
      abdomen-pelvis CT, it was 7.3 to 31.5 (average 16.3) mSv. Reference dose values
      were calculated for each exam. These DLP values are as follows: head, 1300 mGy
      cm; chest, 600 mGy cm; abdomen, 920 mGy cm; pelvis, 650 mGy cm; and abdomen
      pelvis, 1100 mGy cm. CONCLUSION: Among hospitals, there was considerable
      variation in the DLP and patient radiation dose for a specific exam. Reference
      doses and patient doses were higher than those found in similar recent surveys
      carried out in the United Kingdom and the European Union. Patient doses were
      similar to those found in a recent survey in Germany.

PMID- 16944682
TI  - Atypical extraspinal musculoskeletal tuberculosis in immunocompetent patients, a
      review. Part I: atypical osteoarticular tuberculosis and tuberculous
      osteomyelitis.
AB  - With the resurgence of pulmonary tuberculosis and musculoskeletal tuberculosis in
      North America and Europe over the last 20 years, the typical pattern of
      extraspinal musculoskeletal tuberculosis has been changing; presentation of the
      disease often mimics that of neoplasia. However, certain radiographic features
      may offer some clues to the more benign nature of the process and its
      inflammatory and infectious nature. Although the diagnosis of extraspinal
      musculoskeletal tuberculosis depends largely on clinical context, it is the
      radiologist's role to guide the imaging workup to initiate the specific treatment
      as early as possible. As in classic extraspinal tuberculosis, delayed diagnosis
      may lead to deformity of the involved joint and permanent disability. This review
      considers atypical osteoarticular tuberculosis and tuberculous osteomyelitis. We
      discuss examples of these atypical presentations. All patients were permanent
      residents in Europe and North America, and all were immunocompetent.

PMID- 16944683
TI  - Uterine artery embolization--inpatient and outpatient therapy: a comparison of
      cost, safety, and patient satisfaction.
AB  - OBJECTIVES: To determine whether uterine artery embolization (UAE) can be safely
      performed as an outpatient procedure without increased complications and
      readmission rates or decreased patient satisfaction rates and to determine the
      Canadian cost difference between performing UAE as an outpatient, compared with
      inpatient, procedure. METHODS: We performed a retrospective chart review and
      patient survey of 2 groups of patients, 132 patients who underwent inpatient UAE
      and 20 patients who underwent outpatient UAE. Of these, 82 and 18, respectively,
      were successfully surveyed by telephone. Variables examined included presenting
      complaints, postprocedural symptoms, patient satisfaction, and readmission or
      complication rates. We also performed a detailed Canadian cost analysis comparing
      inpatient with outpatient UAE. RESULTS: We did not find any statistically
      significant difference between inpatient and outpatient UAE on any of the patient
      variables measured, including presenting complaints, postprocedural symptoms,
      patient satisfaction, and readmission or complication rates. We also found that
      outpatient UAE costs significantly less than inpatient UAE, primarily owing to
      decreased hospital overhead costs for overnight admission. In Ontario, inpatient
      UAE costs per patient totalled dollars 3216.22, whereas outpatient costs totalled
      dollars 2194.53--a saving of dollars 1021.69, which represents a 31.8% cost
      reduction. CONCLUSION: Given these results, we recommend that centres consider
      performing UAE as an outpatient procedure. A key enabling factor is the ability
      to have several hours of close nursing supervision of the patient postprocedure,
      prior to discharge.

PMID- 16944684
TI  - A web-based test of residents' skills in diagnostic radiology.
AB  - PURPOSE: To develop an objective, Web-based tool for evaluating residents'
      knowledge of diagnostic radiology. METHODS: We developed and tested a Web-based
      evaluation tool (the Diagnostic Radiology Skills Test) that consists of 3 tests,
      one in each of 3 domains of diagnostic radiology: chest, gastrointestinal, and
      musculoskeletal imaging. Each test comprises 30 cases representing a range of
      difficulty in the domain, including normal states, normal variants, typical cases
      of common diagnoses, and cases with more subtle findings. Cases are presented
      with a long menu of domain-specific possible diagnoses (response options), each
      coded for diagnostic appropriateness. Our subjects were 21 residents in
      postgraduate year (PGY) 2 to 5 and 11 experts in diagnostic radiology. Subjects
      accessed the tool via a Web site on our Web server. Residents' test results were
      compared for reliability and validity across domain, case, and training level. In
      addition, results were correlated with commonly used established and objective
      evaluation tools. RESULTS: The tool demonstrated consistent monotonic improvement
      in performance with training level. It showed acceptable reliability in
      discriminating between residents at different performance levels, both within and
      across training levels (r= 0.53 within level and 0.69 across levels). Test
      results also had concurrent validity against the American College of Radiology In
      Training Examination, a widely accepted objective assessment tool (r = 0.65, P <
      0.01), and 2 Objective Structured Clinical Examinations (OSCEs) focusing on
      diagnostic skills (r= 0.78 and r= 0.69, P < 0.01, respectively). CONCLUSIONS: Our
      study demonstrates the feasibility of a Web-based, standardized, objective
      assessment method for evaluating residents' performance.

PMID- 16944685
TI  - Answer to case of the month #107. Appendiceal mucocele as a presentation of
      mucinous adenocarcinoma.

PMID- 16944686
TI  - Answer to case of the month #108. Allergic bronchopulmonary aspergillosis.

PMID- 16944688
TI  - [Structural alterations in the human brain in chronic alcohol intoxication].
AB  - Different brain samples were studied in 23 male alcoholics and 14 healthy victims
      who had died of heart and major vessels wounds to determine histological changes
      in the brain and quantitative relations between its tissue structures. The
      complex of histological, stereo- and morphometric examinations has shown that the
      brain of alcoholics is characterized by sclerosis and hyalinosis of the vascular
      branches as well as dystrophic, atrophic and hypertrophic changes of neurocytes.
      Moreover, there were calcinated petrificates and the cysts, foci of
      demyelination, diffuse microglyosis. These alterations are accompanied with
      impairment of quantitative correlations between tissue brain structures. The
      diameter of cerebral capillaries narrows with resultant lessening of vascular bed
      capacity and chronic brain ischemia. The concentration of nervous cells decreased
      because of their progressive atrophy and death while the indices of the glyal
      component development rose. The findings are important for tanatogenesis and
      postmortem forensic-medical diagnosis of alcoholism.

PMID- 16944689
TI  - [Morphological changes in the lungs in chronic drug addiction].
AB  - Morphological studies of the lungs and immune system organs were made in drug
      addicts with narcotic intoxication. Depletion of the central and peripheral
      lymphoid organs was found in most cases. It is shown that morphological changes
      in the lungs in acute and (or) chronic narcotic drug intoxication, the rate of
      acute and chronic inflammatory lung diseases reflect development of lung
      inflammation in the presence of aquired immunological deficiency in terminal
      chronic drug abuse. The documented features of different pathological processes
      in the lungs can improve diagnosis of acute and chronic drug intoxication by
      results of section and histological examinations.

PMID- 16944690
TI  - [Analysis of accidental deaths in mountain tourism and sport according to
      statistics from the Republic of Kabardino-Balkariia].
AB  - Lethal cases in mountain tourism and sports in the Republic of Kabardino-Balkaria
      were studied for 1978-1995. A total of 152 accidental deaths were analysed. Most
      of the victims were males under 30 years of age. The greatest number of the
      accidents took place on Monday, in July and August. Many amateur visitors from
      abroad were among the victims. The main cause of death in the mountains of
      Kabardino-Balkaria for the 18 years studied was multitrauma of the body (69.7%).
      Hypothermia and obturation asphyxia with snow and compression asphyxia due to
      snowbreak account for 11.8 and 13.2% deaths, respectively; lightning killed 4%.
      Combination of high mountain hypoxia with exacerbated chronic somatic disease or
      hypothermia caused death in 1% victims. The authors propose how to improve
      forensic-medical expert examination of accidental death and safety in the
      mountains.

PMID- 16944691
TI  - [Forensic-medical aspects in assessment of damage to health as the result of
      chest and low back spinal traumas].
AB  - By the law of the Russian Federation, forensic medical examination is obligatory
      to assess damage to health in chest and low back spinal traumas. In persons who
      survived spinal trauma the assessment of its severity is regulated by the rules
      of assessment of the severity of bodily damage and harm to health. Difficulties
      arising in this assessment are outlined. Damage to health is proposed to be
      evaluated not only by clinical data on the condition of the patients but also by
      macro- and microscopic results of forensic-medical examination of the dead body,
      by the presence and severity of edema of the spinal cord tissue.

PMID- 16944692
TI  - [Dependence of acute opiate poisoning lethal outcome on the gender, age, and
      duration of addiction].
AB  - The article presents toxicological characteristics of 198 cases of acute
      parenteral poisoning with morphine and heroin in the range of concentrations of
      their metabolites in the blood and urine which occur in practice. Risk of death
      is quantified in the range of possible morphine concentrations in the blood in
      acute opiates intoxication with reference to gender and age. Assessment of the
      criteria of quantitative opiates toxicity was made according to the method of
      logit regression and dose-effect curve suitable for analysis of correlations
      between probability of death and blood concentrations of opiates metabolites.
      Conditional lethal doses in respect to gender and age are calculated.

PMID- 16944693
TI  - [Micromorphometric parameters of human skin as a marker of skin involution in age
      determination in forensic medicine].
AB  - The mathematical analysis of quantitative micromorphometric parameters of
      different human skin sites on section material has revealed a significant age
      related thinning of the skin and its layers, decreased depth of the salivary and
      sweat glands position. It is proposed to use micrometric skin parameters for
      expert examination to define a biological age of the examinee.

PMID- 16944694
TI  - [Relationships between size and shape of the face with somatic type in women].
AB  - We studied correlations between size of the face, different complexes of somatic
      signs and constitutional types according to the I.B. Galant's scheme basing on
      the materials of a complex anthropometric examination of 1153 Russian girls 16-21
      years of age. We found a mean level of correlations (maximum 0.5 of the
      coefficient of canonic correlation) between the parameters of various
      morphological subsystems "face-body" The factorial analysis allowed us to obtain
      two integrative indices describing a total size and shape of the face.
      Statistical processing revealed a trend to macroprosopia in the groups from
      leptosomic to megalosomic constitutional types of girls from the Galant's scheme
      (p < 0.001). The athletic girls have more pronounced maxillofacial (visceral)
      part and a reduced size of the frontal face. For application in forensic-medical
      practice we present equations for individual estimation of the variant of a total
      size and shape of the face as well as female somatotype.

PMID- 16944695
TI  - [Possibilities of spectral investigations of injuries inflicted by special arms].
AB  - Quantitative characteristics and application of different spectral methods are
      compared in experiment. Stab and gunshot wounds were studied by roentgenospectral
      fluorescent and emission spectral analyses. The above spectral methods detected
      significant quantities of alien material on the wounds depending on the kind of
      the weapon.

PMID- 16944696
TI  - [Blood reinfusion as an indicator of time-limit in the development of splenic
      injuries].
AB  - Literature data are analysed on the causes of differencies often encountered in
      practice between the time of injury by histological examination and time
      established in the course of legal investigation. An indirect marker--blood
      reinfusion--can limit the time of splenic damage creation.

PMID- 16944697
TI  - [The diagnosis of an ABO(H) ABSe group in the traces of saliva, sperm and vaginal
      secretion using mixed agglutination reaction].
AB  - Experimental spots of the saliva, sperm, vaginal secretion from persons with
      groups Ase, Bse, ABSe and Abse were studied with mixed agglutination reaction
      (MAR) using hemagglutinating sera anti-A and anti-B (heteroimmune, isoimmune),
      monoclonal antibodies. MAR with monoclonal antibodies was able to diagnose ABSe
      group not only in the spots of saliva, but also in the spots of sperm and vaginal
      secretion where heteroimmune sera failed.

PMID- 16944698
TI  - [Isolation of lambda-cyhalothrin from biological material].
AB  - Dioxan is proposed as an isolating agent for isolating lambda-cytalotrin (LC)
      from biological material. Optimal conditions for isolating LC from cadaveric
      hepatic tissue with dioxan were determined and the results of the isolation were
      quantified.

PMID- 16944699
TI  - [Differentiation of splenic injuries by the time of their infliction].

PMID- 16944700
TI  - [Visceral alterations in acute blood loss in forensic-medical practice].

PMID- 16944701
TI  - [Forensic-medical service in Leningrad in the years before World War II and
      during the Blockade].

PMID- 16944702
TI  - [Meeting of Main Forensic-Medical Experts of the Health Control System of the
      Russian Federation Subjects and Chiefs of Forensic Medicine Departments:
      "Organisation of Forensic-Medical Expertise of Environmental and Technogenic
      Disasters and Terrorist Attacks Entailed Wounds and Massive Loss of Lives" in
      (March 29-April 1, 2005, Rostov-on-Don)].

PMID- 16944703
TI  - [Clinical and functional parallels and screening for chronic obstructive lung
      disease].
AB  - A difficulty in the timely diagnosis of obstructive lung disease is a problem of
      modern medicine. The disease gradually develops through the years and manifests
      when bronchopulmonary system cannot be restored. The paper presents a method of
      early diagnosis of obstructive lung disease, assesses various procedures, and
      characterizes their informative value. There is evidence that the significance of
      routine functional tests increases with the progression of the disease. The
      simplicity of these tests and their assessment will assist a general practitioner
      to establish the diagnosis in time.

PMID- 16944704
TI  - [Prediction of the course of acute purulent diseases of the lung and pleura].
AB  - The paper presents the data of examination of 62 patients with acute purulent
      diseases of the lung and pleura (abscess, empyema, pyopneumothorax). The
      persistent and virulent characteristics of causative agents isolated just from a
      suppuration focus during its puncture are described. There was an association of
      the high level of antilysozyme, anticomplementary, and hemolytic activities of
      bacterial pathogens with the severe course of a disease. On this basis, a
      mathematical model that can predict the course of acute purulent diseases of the
      lung and pleura with an accuracy of as high as 95% has been constructed.

PMID- 16944705
TI  - [Annual time course of hemostatic changes in patients with respiratory
      sarcoidosis treated with glucocorticoids].
AB  - The time course of changes in the hemostasiological parameters of peripheral
      venous blood was estimated in patients with different forms of respiratory
      sarcoidosis treated with glucocorticoids. A tendency for hypercoagulation was
      found at the onset of the disease. During therapy the trend was towards
      hypocoagulation in most patients. The study of hemostasis supplements and refines
      sarcoidosis patients' functional status that changes under the influence of the
      illness.

PMID- 16944706
TI  - [Effect of theophylline on respiratory function in patients with chronic
      obstructive lung disease].
AB  - The purpose of the investigation was to study the effects of small (200-mg) and
      mean (600-mg) daily doses of theophylline on respiratory function and the quality
      of life in patients with chronic obstructive lung disease during its relatively
      long-term therapy. By the end of the third month of therapy, dyspnea ameliorated
      and life quality increased in both groups of patients receiving both small and
      mean doses of theophylline. This was accompanied by the improved parameters of
      bronchial patency. Thus, forced expiratory volume in one second increased up to
      70.4 +/- 3.9 and to 78.2 +/- 4.8%, respectively, as compared to the baseline
      volumes that were equal to 54.2 +/- 4.3 and 58.4 +/- 4.7%. It should be noted
      that these effects were more pronounced in the mean daily theophylline dosage
      regimen. Relatively long-term therapy with theophylline in daily doses of 200 and
      600 mg was well tolerated. The occurrence of minimum side effects did not prevent
      the drug from being used long in any case.

PMID- 16944707
TI  - [Trend in the gender-age structure of tuberculosis morbidity over 10 years in the
      Russian Federation's areas followed up by the Central Research Institute of
      Tuberculosis, Russian Academy of Medical Sciences].

PMID- 16944708
TI  - [The epidemic drug-resistant tuberculosis situation among the children and
      adolescents of Moscow].

PMID- 16944709
TI  - [Impact of active detection and treatment of patients with tuberculosis on fatal
      outcomes].
AB  - The influence of medical factors, such as active detection of the disease and
      therapeutic efficiency within the first-year follow-up, on the outcome of
      tuberculosis was studied. It was ascertained that about half the patients with
      active tuberculosis could not be undetected if goal-oriented measures to attract
      persons to screening were not made. Fatal outcomes were more common in patients
      with untimely diagnosed disseminated tuberculosis with bacterial isolation and
      decay. The patient's awareness of the disease and readiness to contact medical
      staff are of great importance for good results of therapy and recovery.

PMID- 16944710
TI  - [Causes of death from fibrocavernous pulmonary tuberculosis in the Sverdlovsk
      Region].
AB  - In the Sverdlovsk Region, the main reason of death from tuberculosis is a
      fibrocavernous pulmonary process (51.8%) that is most commonly detected in the
      postportem diagnosis of tuberculosis (61.9%). Before death, patients with
      fibrocavernous tuberculosis do not ask for medical aid frequently (73.4%). In the
      first-year follow-up, most deceased persons come to health care facilities 3
      months or more after the occurrence of significant clinical symptoms (60.8%). The
      refusals of patients to receive in- and outpatient therapy, multiple discharges
      from hospital due to their incompliance, following by long-term therapy
      discontinuance, which led to secondary multidrug resistance, were responsible for
      progressive tuberculosis that was the main cause of death from a fibrocavernous
      process.

PMID- 16944711
TI  - [Impact of the area burden of agrochemicals on tuberculosis morbidity and
      mortality].
AB  - The rate of use of pesticides and mineral fertilizers in the Republic of
      Daghestan was high in the USSR and Russia and was many times greater than the
      critical burden (3/93 kg/ha) and ranged from 3.5-4.2 kg/ha in the highlands to
      17.0-21.7 kg/ha in the plain. Two-factor analysis indicated that out of the
      mineral fertilizers, pesticides and phosphate fertilizers had the most adverse
      effect on the incidence of tuberculosis whereas potash fertilizers exerted a less
      effect. Phosphate fertilizers and copper-containing pesticides were secondary
      risk factors of death from tuberculosis. The correlation coefficient was 0.53 for
      phosphate fertilizers, 0.59 upon total exposure to organochlorine compounds, and
      0.68 upon total exposure to copper-containing pesticides.

PMID- 16944712
TI  - [Organization of hospital care to patients with tuberculosis concurrent with HIV
      infection in Tuberculosis care hospital No. seven].
AB  - HIV-infection morbidity rates continue to increase in Moscow, the Moscow Region,
      and in the whole country. The epidemiological situation associated with
      tuberculosis concurrent with HIV infection remains tense in Moscow and its
      region, as judged from the data of an analysis of this disease at tuberculosis
      hospital seven (TH-7) over 9 years. A total of 411 patients with tuberculosis
      concurrent with HIV infection were treated at TH-7 in 1996 to December 2004.
      Among them, 49.6% were Moscow residents, 15.1 and 26.5% of the patients lived in
      the Moscow Region and other regions of the Russian Federation, respectively; 6.8%
      were homeless persons and 2% foreigners. The number of patients with tuberculosis
      concurrent with HIV infection has been annually increasing at TH-7. Among the
      total number of patients, their proportion was 13.4% in 2004. In the structure of
      patients with comorbidity, the proportion of surgical patients has been on the
      rise and it was 51.8% in 2004. Among the surgical patients with tuberculosis
      concurrent with HIV, the proportion of patients with generalized (multiple organ)
      tuberculosis has increased; it was 50% in 2004. Patients with tuberculosis
      concurrent with HIV infection need a greater scope of surgical interventions al
      number of patients for therapeutic and diagnostic purposes.

PMID- 16944713
TI  - [Problems in the diagnosis and surgical treatment in an osseous tuberculosis
      hospital].
AB  - The diagnosed patients treated at an osseous tuberculosis hospital are analyzed.
      In the reporting period, the diagnosis of osseous tuberculosis has not been
      verified. Late detection of osseous tuberculosis, as its prehospital
      hyperdiagnosis is one of the main reasons of a grave condition in this group of
      patients. The paper characterizes plastic reparative versus palliative
      decompressive operations for tuberculous spondylitis with spinal-cord
      abnormalities and shows that radical surgery has a higher efficiency (89%) in the
      treatment of an inflammatory process and in the regression of neurological
      complications. In generalized forms of osteoarticular lesions if there is an
      indication for surgical treatment, long-term drug therapy for tuberculosis of the
      lung and other organs is not warranted.

PMID- 16944714
TI  - [Forced oscillation technique in the study of a bronchial response in patients
      with tuberculosis during drug test using berotec].
AB  - A comparative study of the data obtained from the use of forced oscillation (FO)
      technique, spirography (SG), flow-forced expiratory volume (F-FEC) curve
      recording has provided evidence that the FO technique is highly effective in
      assessing a drug test. The FO technique revealed changes in bronchial patency in
      69.5% of patients with bronchial obstruction whereas F-FEV recording indicated
      this pathology only in 42.4% (p < 0.05). A concurrent use of the pooled values of
      viscous respiratory resistance, SG, F-FEV curve to assess the results of a
      broncholytic test could diagnose bronchospasm in 79.7% of patients with pulmonary
      tuberculosis with impaired bronchial patiency.

PMID- 16944715
TI  - [The clinical and morphological features of pulmonary tuberculosis under the
      conditions of the Far North].
AB  - The clinical and morphological features of pulmonary tuberculomas were studied in
      205 patients among the naives and newcomers of the Far North. It was established
      that the lymphohematogenous spread of tuberculosis involving mainly the lymphatic
      system into the inflammatory process predominates in the genesis of tuberculomas
      under the conditions of the Far North. At the same time the lymphatic genesis of
      tuberculosis was found to affect the development of pulmonary tuberculomas in 60%
      of cases among the native patients. In most patients, the afflicted intrathoracic
      lymph nodes became a source of retrograde dissemination of tuberculosis in the
      lung. Tuberculomas were chiefly unilateral and in 56.7% of cases they were
      located in the lower portions of the lung in the presence of significant
      fibrosis. The lymphohematogenous spread of tuberculous infection was a cause of
      pulmonary tuberculomas in most (72.9%) newcomers on adapting to the conditions of
      the Far North. In most cases, tuberculomas were formed from a newly appeared
      tuberculous focus in the presence of intact lung tissue and located in the upper
      portions of both lungs. The formed tuberculomas had no extensive focal
      dissemination and were present within the anatomic structure of one or two
      segments of the lung.

PMID- 16944716
TI  - [Leiomyomatosis of the lung].
AB  - The paper describes a case of diffuse leiomyomatosis of the lung in a 45-year-old
      female. Leiomyomatosis, a disease noted in females, is considered to include 4
      types of multiple smooth muscle lesions: 1) benign metastasizing leiomyoma; 2)
      lymphangioleiomyomatosis; 3) leiomyomatous peritoneal dissemination; and 4)
      intravenous leiomyomatosis. The authors present a classification proposed by E.
      Martin who attempts to pool in it all multiple leiomyomatous lesions observed in
      females, males, and children.

PMID- 16944717
TI  - [Tuberculosis-controlling service in the Tyumen Region from its setting-up to the
      present day].

PMID- 16944718
TI  - [Study of the platelet and plasma systems of hemostasis in patients with
      pulmonary tuberculosis].

PMID- 16944719
TI  - [Determination of multidrug resistance of Mycobacterium tuberculosis by molecular
      biological studies].

PMID- 16944720
TI  - GMP Wireless Medicine LifeSync wireless ECG system.
AB  - Wireless technology is a growing presence in medical applications. A recent entry
      in the field is the LifeSync Wireless ECG System manufactured by GMP Wireless
      Medicine. The LifeSync transmits electrocardiogram (ECG) and respiration
      waveforms wirelessly from the patient to a physiologic monitoring device (bedside
      monitor, transport monitor, or 12-lead ECG cart), allowing the elimination of
      traditional ECG leadwires connecting the patient to the monitoring device. This
      wireless ECG monitoring is designed to reduce restrictions on patient movement,
      ease transport, and simplify clinicians' lives compared to the use of traditional
      hardwired ECG systems. Our Evaluation examines whether, in fact, the LifeSync
      accomplishes these goals. Most of our findings focus on ease-of-use issues,
      although cost also carries significant weight in our judgments. The LifeSync's
      lead set, the LeadWear Disposable Cable Replacement System, is disposable and
      radiolucent, and its electrodes are all connected along a single cable rather
      than being separate strands. In addition to its use with the full LifeSync
      system, the LeadWear can also be used by itself--without the wireless component
      in place of standard ECG leadwires. Our Evaluation includes a separate rating for
      using the LeadWear in this way, in what we call the LeadWear-only approach.

PMID- 16944721
TI  - Anesthesia systems for ambulatory surgery settings.
AB  - This Evaluation presents ECRI's detailed findings for two anesthesia systems
      designed for the ambulatory surgery market-the Datex-Ohmeda S/5 Aespire 7100 and
      the Draeger Medical Fabius Tiro. The study examines whether and how well the
      systems can meet the needs of the typical patient population for this
      application, and it considers factors such as the adequacy of the systems' safety
      features, the comprehensiveness of their pre-use checks, and ease of use. We
      subjected the two systems to the same test protocol that is detailed in our July
      2006 Evaluation of anesthesia systems designed for inpatient surgical
      applications. While the six systems evaluated in that issue could also be used in
      outpatient clinics and other ambulatory surgery centers, such systems are not the
      most economical choices for these facilities. The two systems we evaluate in the
      current study offer performance similar to that of the inpatient units, without
      many of the (often expensive) features that would likely go unused in an
      ambulatory surgery setting.

PMID- 16944722
TI  - Hazard report. Incompatibility of IV therapy products impedes IV fluid flow.

PMID- 16944723
TI  - [The effect of myocardial bridging on the incidence of coronary
      arteriosclerosis].
AB  - In this paper we dissected 50 human hearts obtained from the Department for
      Anatomy and Department of Forensic Medicine and Pathology, Faculty of Medicne,
      Sarajevo. Our interest was to show frequency of myocardial bridging on human
      heart coronary artery branches, their localisation and dimensions. Cross sections
      of coronary arteries segments in area of bridges, proximal and distal to it, were
      taken out from hearts on which dissection method showed presence of myocardial
      bridging of the coronary artery branches. Cuts were made 5microm-tick and
      coloured by Hematoxylin-eosine, Elastica Van Giesson, and Ladewig after having
      been fitted into paraffin wax. Preparations were behold mocroscopically and flow
      direction of myocardial bridge muscle fibres was followed regarding the artery
      wall, and it was analysed artery wall structure in the myocardial bridge area,
      proximal and distal to the bridge. Myocardial bridges werw found in 42% examined
      cases, and with the most frequent localisation on ramus interventricularis
      anterior (34%). Atherosclerotic change in the artery segments proximal to the
      myocardial bridge was detected by the histolopathological method and its
      intensity depended on the myocardial bridge length and years of age. In the area
      of the myocardial bridge, besided insignificant diffuse intima, there were not
      any other histopathological changes that would indicate an atherosclerotic
      process.

PMID- 16944724
TI  - [Variable anatomy of the kidneys--relationship and incidence between anatomical
      and clinical three-dimensional image methods].
AB  - Research has been done at a 150 pairs of the human adult kidneys (50 anatomical
      preparedness plus 100 patients) both sex, randomly chosen. Variations of the
      kidneys have been analyzed and their respect at a live ones, by clinical tree
      dimensional "image"methods and lifeless one by anatomical macro dissection plus
      corrosive method. CONCLUSION: At the most presence of noticed variation had into
      a size of the kidney, and the lowest one in the number of the kidneys. Technique
      of magnetic resonance (MR), in relation with computerized tomography (CT) had
      shown more types of the kidneys variations and more number of the kidney's
      variations in the form. Percentage of variations of the kidneys at an anatomical
      preparedness in relation with variations noticed by MR and CT, into a size had
      relation 44: 4: 0, in the form of 36: 6: 2, in the number 0: 2: 0 and into a
      location ( rotation) 0: 0: 4. The number and the type of noticed variations of
      the kidneys show the largest presence at an anatomical matiarials assigned by
      anatomical macro dissection and corrosive technique in relation with noticed
      variations of the kidneys by MR and CT. Because of that anatomy finding are set
      as an imperative into methodological researches of variable anatomy of the
      kidneys.

PMID- 16944725
TI  - [Morphological research of fibrinoid and intervillous space of human term
      placenta in relation to the age of pregnant woman].
AB  - Fibrinoid and intervillous spaces of the mature human placenta were
      morphologically and quantitatively examined in pregnant women of different ages.
      The aim of this research was to compare the results and to confirm if there is
      some quantitative difference between fibrinoid and intervillous spaces of
      placenta related to the age of pregnant women. The examined group of women were
      of age between 20 and 45 years, and they were divided into two groups: 1)
      pregnant women 20-35 year old; 2) pregnant women over 35 years old. The volume
      density and absolute volume of fibrinoid and intervillous space of placenta were
      stereologically examined. Volume densities of fibrinoid and intervillous space of
      placentas in older pregnant women compared to younger is significantly increased.
      Absolute volumes of fibrinoid and intervillous space of placentas in younger and
      older pregnant women are not significantly different.

PMID- 16944726
TI  - [Eosinophil-derived neurotoxin as a new additional clinical marker in spinal
      muscular atrophies].
AB  - INTRODUCTION: Spinal muscular atrophies (SMA) are group of neuromuscular
      disorders characterized by degeneration of motorneurons in anterior column of
      medulla spinalis, and sometimes in motoneurons of cranial nerves and the brain.
      Causes of SMAs are mutations in genes encoding for SMN, SIP and NAIP that are
      very low in motorneurons of these patients. Ribonucleases (RNases) are enzymes
      that depolimerize RNA and may destabilize DNA. AIM: The objective of this study
      was to determine ribonuclease activity in serum and urine of SMA patients.
      METHODS: RNases were purified by anion-kation-exchange chromatographies, and
      HPLC, and their activity was measured by immunodetection using specific
      antibodies against rinonucleases in presence of RNA as a substrate. RESULTS:
      Eosinophil-derived neurotoxin (EDN) activity iin serum of SMA patients was 5.6,
      3.8 and 2.6 higher in type I, II and III comparing with control group. RNase
      inhibitor activity in serum of the same patients was 3.0 and 2.4 lower in type I
      and II vs. Control group, but in type III was unchanged. Similar results are
      found in urine of the same patients. CONCLUSION: Increased serum and urin EDN
      activities in SMA patients could be used as a new additional clinical marker in
      their diagnosis.

PMID- 16944727
TI  - [The effectivness of direct observed treatment short course (DOTS) in
      tuberculosis treatment].
AB  - In 1994 the National Tuberculosis (TB) Programme of our country adopted direct
      observed treatment short course (DOTS) as National TB control strategy. After
      that DOTS has been implemented in different parts of country. OBJECTIVE: to
      define the effectiveness of DOTS strategy implementation in Sarajevo Canton.
      PATIENTS AND METHODS: Medical histories and treatment cards of TB smear patients
      admitted in the University Clinic Sarajevo during 1998 and 1999, as well as
      Referral Microbiological Laboratory Registers of Federation of Bosnia and
      Herzegovina were used for the analysis. The control group consisted of patients
      treated in the area which covers present Sarajevo Canton in the period when DOTS
      strategy was not used. RESULTS: In 1998 there were 83.6 % new TB cases and 89.5 %
      in 1999. The smear sputum conversion rate was 89.5 % in 1998 and 93 % in 1999.
      Smear sputum conversion rates were achieved in the period of 30-45 days after
      antituberculous treatment onset in 50.0 % patients in 1998 and in 51.7 % in 1999.
      Chest X-ray partial regression in the initial phase (at the end of second month
      of treatment) was achieved in the examined groups in higher percentages (70.1 %
      in 1998 and 77.9 % in 1999.) compared with the control group (44.29 %). It was
      evident that partial radiographic regression was achieved up to 45 days after
      treatment onset in the examined group in 42.6 % cases in 1998 and in 61.2 % in
      1999. In this period in the control group partial radiographic regression was not
      achieved at all. Total chest X-ray regression was achieved neither in examined
      groups nor in control group. CONCLUSION: These data are the results of
      successfulness of the DOTS treatment.

PMID- 16944728
TI  - [Pancreas and laparoscopy].
AB  - Number of studies were performed about pneumoperitoneum effect formed during
      laparoscopic surgery to the function of thoraco-abdomininal organs. However,
      studies about influence of pneumoperitoneum to the pancreas function are very
      rare. This is just what this study is about. Two groups of patients are included
      in the study: examined group of about 30 patients who had holecistectomy
      performed by laparoscopic surgery technique, and the control group (30 patients)
      who had holecistectomy performed by the laparotomic technique. Activity of the
      pancreas amylases was controlled 2, 6, 24, 48 and 72 hours, for the patients from
      both groups, before and after the surgery. CONCLUSION: After statistic analysis
      of gained data it was not possible to prove that pneumoperitoneum with a pressure
      of 15 mmHg has influence to the excretory pancreas function.

PMID- 16944729
TI  - [Antegrade warm blood cardioplegia compared to crystalloid cardioplegia in
      myocardial protection].
AB  - The tehniques of myocardial protection in cardiac surgery are innumerable. In
      this trial we tried to compare two established cardioplegic strategies in
      elective on-pump surgery (Intermittent antegrade warm blood cardioplegia-
      Calafiore--) and Kirsch-Solution with Haes). We took the data from our medical
      documentaton for 115 patients who underwent elective on-pump surgery in time
      period from February 2005 to July 2005.

PMID- 16944730
TI  - [Surgical treatment of juvenile nasopharyngeal angifibroma].
AB  - Juvenile nasopharyngeal angiofibroma represents non-incapsulated benign tumor. It
      can lead to serious problems with the extension into nearest structures.
      Recidivism is described in 20 to 30 % of cases, after surgical or other adjuvant
      therapy. Three patients with juvenile nasopharyngeal angiofibroma that underwent
      surgery in a five year period (2001-2005) at the ENT Clinic of the University
      Clinical Center in Sarajevo are evaluated in this paper. No complications were
      encountered during surgical procedure and early postoperative period. Recidivism
      are not noted two years after the surgery. Surgical method of choice in stage IA
      and IB is combined transnasal-oropharyngeal technique. Other surgical procedures
      are used for more extensive processes.

PMID- 16944731
TI  - [Hepatitis C virus infection in hemodialysis patients in General Hospital
      Gracanica].
AB  - PURPOSE: It is estimated that 10-20 % patients on hemodialysis therapy have
      hepatitis C virus infection with big geographic and individual variability in HCV
      prevalence between different hemodialysis centers. OBJECTIVES: To determine
      prevalence of HCV infection among hemodialysis patients in Hemodialysis Unit of
      General Hospital Gracanica and to make epidemiological, clinical, biochemical and
      virusological analysis in anti-HCV positive patients. WORK METHODS: 58 patients
      that were hemodialyse during 2000 year in Hemodialysis Unit Gracanica were
      included in this study. All patients were tested on anti-HCV antibody and further
      planed analyses were done. WORK RESULTS: Prevalence HCV infection in Dialysis
      Unit Gracanica was 46.5 %. The most number of HCV positive patients were in age
      of 40-49 years 40.7 % or (11/27 patients). The more often HCV positive patients
      were male 59.3 % or (16/27 patients). In group of anti-HCV positive patients, in
      85 % (23/27) have detected HCV RNA. It means that 39.60 % patients in
      Hemodialysis Unit Gracanica have chronic HCV infection, but 6.80 % patients had
      past infection. Receiving of blood transfusion, as risk factor, for HCV infection
      were more often found in group anti HCV + patients (81.5 %) than in group anti
      HCV negative patients (51.6 % patients). The length of dialysis therapy were
      longer in group anti HCV + patients and it was 6.8 years than in group of anti
      HCV negative patients that was 1.6 years. HCV infection was not associated with
      significant biochemical parameters of liver lesion or with manifested clinical
      symptoms in the time of this study. CONCLUSION: The observed Unit for
      Hemodialysis can be concerned as unit with high prevalence of HCV infection. It
      is courage fact that there was no new registered HCV seroconversion since
      beginning of work this unit until time of this study. Implementation of general
      and specific measures for prevention of HCV infection and introduction of regular
      control can decrease risks for HCV infection inside hemodialysis unit.

PMID- 16944732
TI  - [Frequency of microsporidial Encephalitozoon intestinalis in patients with
      diarrhea].
AB  - Encephalitozoon intestinalis is an obligate intracellular sporeforming protozoa
      belonging to the order Microsporidia of the phylum Microspora. In the year 1923
      Levadetia et al., using transmision electron microscopy, for the first time,
      identified microspridial organism, Encphalitozon intestinalis as causing acute
      diarrhea. Encephalitozzon-like spores were also found in cerebrospinal fluid in
      rabits. Three species have been identified in order Encephalitozoon firstly named
      Sepatata intestinalis and later renamed in Encephalitizon spp. by Didier.
      Thereafter, numerous reports have sugested that microspridial infections may be
      responsible for many cases of diarrhea esspecialy in patients with AIDS. Only
      rarely have microsporidial infections been found in non-HIV infected individuals.
      The aim of our study is to detect microsporidian protozoal parasite
      Encephalitozoon intestinalis as a cause of acute diarrhea in non HIV-infectid
      patients in Slovenia.

PMID- 16944733
TI  - [Adolescents and knowledge of sexually transmitted diseases in Tuzla Canton].
AB  - INTRODUCTION: Sexually transmitted diseases today are the most spread infectious
      diseases. Their incidence is constantly increasing. Usually they affect the
      population age 15 to 19. OBJECTIVE: To examine and determine parameters related
      to sexual behavior (sexarcha, duration of sexual activity, number of sexual
      partners), knowledge of adolescents of Tuzla Canton about sexually transmitted
      diseases and how do they get informed about it. MATERIAL AND METHODS: In period
      June to September 2003 we conduct a survey with 2995 high school boys and girls
      age 14 to 19 in Tuzla Canton. The survey contained questions about sexarcha,
      knowledge on sexually transmitted diseases, usage and knowledge on methods of
      contraception. RESULTS: Sexually active high school youth was 395 (13,18 %). Of
      that number 306 (10.22%) were boys and 89 (2.9 %) were girls (p<0.001). Average
      age of sexarcha for girls was 16.5+0.97 and for boys 15.7+1.2. Earliest average
      age of sexarcha for girls was in the municipality of Sapna (15.25+0.5) and for
      the boys in the municipality of Teocak (15 +1.1). In undeveloped municipalities
      sexual activity of adolescents of both sexes is significantly higher then in
      developed ones (p<0.5). High school boys and girls of Tuzla Canton showed
      insufficient knowledge of sexually transmitted diseases. Good knowledge showed
      only 87 (5 %) of girls and 25 (2 %) of boys. Girls showed statistically
      significant better knowledge on sexually transmitted diseases than boys p<0.001).
      Only 208 (19 %) boys and 539 (29 %) girls talks with parents about sexually
      transmitted diseases and contraception. CONCLUSION: Work on education of youth,
      especially in undeveloped municipalities in insufficient, as well as knowledge on
      sexually transmitted diseases and methods of contraception.

PMID- 16944734
TI  - [Model of integrated management of hypertension--population approach].
AB  - Actual transitional moment in Bosnia and Herzegovina has the significant health
      implication. Several population surveys conducted in the past 10 years period
      showed the rather high prevalence of main cardiovascular risk factors, including
      hypertension. It was proof that cardiovascular risk factors are preventable.
      Hence, development and establishment of a model of integrated management of
      hypertension in actual moment in BIH is necessities due to relatively high level
      of prevalence of hypertension and limited financial resources in health sector.
      This paper shows a possible model a model of integrated management of
      hypertension at population level with active participation of actors from three
      managerial levels--strategic, tactical and operational.

PMID- 16944735
TI  - [Hospital outcome in acute coronary syndrome in the period 1987-2001 in West
      Herzegovina canton--retrospective study].
AB  - Objective of the study is to show prevalence of hospital mortality of acute
      coronary syndrome in pre-war (1987-1991), war (1992-1996) and after war period
      (1997-2001) among inhabitants of West-Herzegovina canton living in the following
      municipalities: Siroki Brijeg, Posusje, Grude and Ljubuski (88,992 inhabitants).
      Collected were data on patients who were admitted in the hospital due to acute
      coronar syndrome (category I 20, 21, 22- X revision, ICD) in the above period in
      Mostar. Data were analyzed in regard to sex, age and disease output. Hospital
      morality in 15 year period for both sex were 15.0 %, men 12.1 %, and women 20.2
      %. Statistically it was not found significant differences in the period 1987-2001
      in regards to total hospital mortality of men and women and separate hospital
      mortality of men. Differences were found in women where considerable larger
      number was in pre-war and post-war period in comparison with war period. The
      largest hospital mortality was in total and for women in the pre-war period and
      for men was during the war period. The smallest hospital mortality was in total
      and for women during the war and for men in pre-war period. We find that lower
      hospital mortality in women was caused by lower hospital admission because of war
      time and problems with transport and that larger number of women deceased before
      admission to the hospital.

PMID- 16944736
TI  - [Acute lymphoblastic leukaemia as a secondary malignoma after treatment of acute
      myeloic leukaemia (AML/M4)].
AB  - We report about very rare case of ten years old boy with diagnose of acute
      myeloic leukaemia which was diagnosed in his age of five (March of 2000) at
      Pediatric Clinic in Sarajevo. In the first phase of the complete remission
      autologic bone marrow transplantation was done in Italy (Ancona). Just 7 months
      after transplantation boy had relaps of illness in the form of acute
      lymphoblastic leukaemia (ALL/L2). Complete therapeutic protocol for acute
      lymphoblastic leukaemia was done and now boy is in complete clinical and
      hematologic remission.

PMID- 16944737
TI  - [Fryns syndrome].
AB  - Fryns syndrome is an extremely rare developmental disorder associated with
      deletion of long arm of chromosome 16. Characteristics of the Fyns syndrome are:
      craniofacial dysmorfism, diaphragmatic defects with lung hypoplasia, distal
      digital hypoplasia, brain and urogenital abnormalities and other developmental
      disturbances. After the first description in two stillborn sisters by Fryns
      (1971), new reports appeared with descriptions included disorders which have not
      described previously. We described a case of female live born with deletion of
      long arm of chromosome 16. Our patient had a typical craniofacial dysmorfism,
      brain abnormalities (Dandy Walker malformation), cardiac defects (artial septal
      defect and persistent ductus arteriosus), renal hypoplasia, gastrointestinal
      problems, hypotonia and feeding difficulties. Our patient had no diaphragmatic
      hernia and he survived neonatal period with severe neurological impairment.

PMID- 16944738
TI  - [Have we forgotten neurological diseases with psychological symptoms? Case study:
      Huntington's chorea].
AB  - Huntington's cohrea is neurodegenerative disorder with high incidence of
      different psychiatric symptomathology including mood symptoms, dementia and
      psychotic symptoms. Very often psychic symptoms come before the typical motor
      symptoms. This paper demonstrates difficulties in diagnostic process for
      Huntington's chorea in the case when psychiatric symptoms come before the motor
      symptoms. We should take in account neurodegenerative disorder in the case of
      psychiatric disorder with atypical clinical pictures without adequate response on
      standard treatment.

PMID- 16944739
TI  - [Primary retroperitoneal mucinous cystadenocarcinoma].
AB  - Primary retroperitoneal mucinous cystadenocarcinoma is very rare disease. It is
      very similar to cystadenocarcinoma ovary. Histogenesis of this tumour still
      remains unknown. In our case report tumour was noticed in left retroperitoneum
      during routine ultrasound check of stomach in female patient 43 years old. CT
      studies of kidney, retroperitoneum and pelvis, irigography studies and
      gynecological examination was done additionally.

PMID- 16944740
TI  - [Statins and cardiovascular diseases].
AB  - Statins are utilised in the primary and secondary prevention of coronary heart
      disease, due to their efficacy at lowering lipid levels. However, statins may
      also prevent atherosclerosis disease by non-lipid or pleiotropic effects, for
      example, improving endothelial function by promoting the production of NO. By
      increasing NO production, statins may interfere with atherosclerosis lesion
      developement, stabilise plaque, inhibit platlet aggregation, improve blood flow
      and protect against ischaemia. Therofore, the ability of statins to improve
      endothelial function through the release of NO may partialy account for their
      beneficial effects at reducing the incidence of cardiovascular events. Other
      pleiotropic effects of statins, i.e. immunomedulatory, antiinflammatory,
      antioxidant and antiendothelin effects, also contribute to the reduction of the
      incidence of major cardiovascular events. Statins have become the basic drugs in
      high risk cardiovascular patients with hypercholesterolemia. The ATP III update
      recommends an optional therapeutic target of LDL-C < 1,8 mmol/L in very high risk
      patients: those with acute coronary syndrome or those with CHD plus diabetes, the
      metabolic syndrome, multiple-risk factors, or a poorly controlled risk factor.
      Studies have demonstrated benefit from lipid lowering irrispective of initial LDL
      C levels, including those with average levels at baseline.

PMID- 16944741
TI  - Role of radionuclide imaging in nephro-urology.
AB  - Urinary tract diseases are common problem that, if untraeted may lead to
      progressive renal damage. Interpretation of a dynamic renal study includes
      evaluation of the parenchimal phase, the cortical transit time and the urine
      drainage phase. The diagnosis and management of urinary tract obstruction is an
      important problem in both pediatric and adult urology. For the study of urinary
      tract obstruction, conventional radionuclide renography has been modified to
      include, the administration of a potent diuretic. Dynamic renal study accurately
      reflect the functional status of each kidney.

PMID- 16944742
TI  - [Renal osteodystrophy: diagnostic-therapeutic approach].
AB  - Disturbances in mineral and bone metabolism are common in patients with chronic
      kidney disease (CKD). Patients with CKD almost always develop secondary
      hyperplasia of the parathyroid glands, resulting in elevated blood levels of
      parathyroid hormone (PTH). The processes causing disordered mineral metabolism
      and bone disease have their onset in the early stages of CKD, continue throughout
      the course of progressive loss of kidney function and may be influenced
      beneficially or adversely by various therapeutic approaches used. It is should be
      emphasized that the care of CKD patients with bone disease requires frequent
      assessment of the various parameters (levels of calcium, phosphorus, vitamin D,
      PTH) and frequent evaluation of the therapies.

PMID- 16944743
TI  - [Development of public health in B&H and Sarajevo].
AB  - Public health in B&H has long tradition. In this article authors presented
      development of public health in Sarajevo and Bosnia and Herzegovina.

PMID- 16944744
TI  - [Scheme of hemopoiesis 2005].

PMID- 16944745
TI  - [Efficacy and safety of transfusion therapy in hematological patients].
AB  - AIM: To determine whether probability of hepatitis B and C virus (HBV/HCV)
      infection of hematological patients depends on intensity of hemotransfusion
      therapy and to propose possible ways to diminish posttransfusion risk of virus
      infection with HBV/HCV. MATERIAL AND METHODS; A clinicoepidemiological
      prospective trial was made to monitor risk factors and indicators of HBV and HCV
      infection in 216 patients of a hematological department of the Hematological
      Research Center. A total of 447 hospitalizations (229 rehospitalizations among
      them) to the department of chemotherapy, depression of hemopoiesis and bone
      marrow transplantation for 2 years were analysed. Statistics were analysed using
      SAS computer programs and the "landmark method". RESULTS: Transfusions of blood
      components before initiation of the trial were performed in 201 (93%) patients,
      120 (60%) patients received more than one transfusion (median of the number of
      donors was 40). Markers of virus hepatitis were initially detected 1 month after
      hospitalization in 103 (47.7%) patients: HCV--in 26 (12%), HBV--in 77 (35.6%); 18
      (17.5%) patients were coinfected (HBV/ HCV). Probability of detection of HBV and
      HCV markers in patients with multiple transfusions was significantly higher than
      in patients with a short transfusion history (50% probability of HBV and HCV
      infection was 153 and 251 days, respectively, p = 0.059). CONCLUSION: Reduction
      of aftertreatment lethality and, finally, treatment efficacy in hematological
      patients depends on adequacy of replacement therapy with blood components,
      platelets first of all. High percentage of HBV and HCV infection confirms
      dependence of infection probability on the number of donors. Thus, patients with
      planned massive replacement therapy should be provided with specially selected
      donors. Blood for transfusion for them should be examined for viruses repeatedly.

PMID- 16944746
TI  - [Characteristics of T-cell immunity in patients with acute leukemia].
AB  - AIM: To study a cytokine profile of cytotoxic T-cells and T-helpers at diagnosis
      of acute myeloid and lymphoblastic leukemia (AML and ALL) and at different stages
      of its treatment. MATERIAL AND METHODS: T-cell population of peripheral blood
      lymphocytes was studied in 19 AML patients at diagnosis, 13 AML patients in
      remission, 5 AML patients in developing recurrence and 5 ALL patients at
      diagnosis. The control group consisted of 10 healthy donors. A mononuclear
      fraction of peripheral blood cells was stained with monoclonal antibodies.
      Surface expression of CD3, CD4, CD8 antigens was estimated with the use of flow
      cytofluorimeter FACS Calibur. Part of the cells were cultured for production of
      activated lymphocytes. The cytokine profile of T-cells was investigated according
      to the modified method of Rostaing et al. in the population of CD3+CD8+ and
      CD3+CD8- T-cells using the flow cytofluorimeter FACS Calibur. The results were
      processed with the programs CellQuest and WinMDI, Statistica Module Switcher.
      RESULTS: The percentage of CD3+CD8+ cells producing interferon-gamma (IF-g) was
      the same in AML patients and donors. The percentage of CD3+CD8- cells (T-helpers)
      producing IF-g was similar in the patients at diagnosis and in complete remission
      being higher than in healthy donors. The number of CD3+CD8- cells producing IF-g
      was reduced in recurrence while the number of CD3+CD8+ and CD3+CD8- cells
      producing interleukin-4 (IL-4) increased. In the onset of the disease, ALL
      patients had significantly increased percentage of CD3+CD8- IL-4 cells.
      CONCLUSION: The results obtained evidence for different polarization of T-cell
      immunity in AML and ALL patients at the time of diagnosis, remission and
      recurrence: in the onset of AML there was an increase in the production of Th1-
      proinflammatory cytokines, in ALL--in percent of Th-2 cytokines. In AML
      recurrence the balance of cytokines shifted in the direction of Th-2 response.

PMID- 16944747
TI  - [Monitoring of minimal residual disease in patients with acute promyelocytic
      leukemia].
AB  - AIM: To study efficacy of different programs of maintenance therapy, to create
      the program of differential therapy of minimal residual disease (MRD) and
      molecular recurrences at all stages of acute promyelocytic leukemia (APL) basing
      on the results of monitoring. MATERIAL AND METHODS: A total of 76 APL patients
      entered the trial. They received therapy by the protocols APL-97/98, APL-01,
      AIDA, 5D. Expression of chymeric oncogen PML/RARa in the disease onset was
      estimated by bone marrow and/or peripheral blood examination with RT-PCR. The
      study of chymeric oncogen PML/RARa was made once in two months. RESULTS: The
      program of differential therapy of APL is proposed on the basis of molecular
      biological monitoring of expression of chymeric oncogen PML/RARa. The results of
      molecular monitoring of MRD correlated with development of molecular and
      hematological recurrences. Therapeutic policy is determined after diagnosis of
      molecular recurrence. Further therapy of APL is determined which allows a rise in
      overall and recurrence-free survival of the patients. CONCLUSION: The efficacy of
      maintenance therapy only with cytostatic drugs or their combination with ATRA is
      similar. The response to biological therapy with ATRA plus interferon-alpha is
      not sufficient. Molecular recurrences--probable or documented--are detected in
      maintenance therapy 2 months earlier, on the average, than hematological ones.
      Changes in the treatment policy in registration of molecular recurrence
      significantly diminish probability of hematological recurrence (from 36 to 0%, p
      = 0.001.

PMID- 16944748
TI  - [Clonal chromosomal aberrations in patients with aplastic anemia at the disease
      onset and transformation].
AB  - AIM: To estimate detectability and characteristic features of chromosomal
      aberrations in bone marrow cells of patients with aplastic anemia (AA). MATERIAL
      AND METHODS: The trial covered 155 AA patients admitted to the Hematological
      Research Center in 1987-2002. Cytogenetic study by G-differential staining was
      performed in 58 patients with AA and 5 patients with AA transforming into
      myelodysplastic syndrome (MDS) or acute leukemia (AL). Cytogenetic and
      morphological specimens of the latter's bone marrow were studied retrospectively
      using fluorescent in situ hybridization (FISH) with DNA probes for detection of
      monosomia 7 and deletion 7q. RESULTS: Clonal chromosomal aberrations were
      detected in 4 out of 28 patients. Further examinations revealed no aberrations.
      Clonal diseases developed in 7 (4.5%) of 155 patients. In 2 patients the disease
      transformed into paroxysmal nocturnal hemoglobinuria, 5 (3.2%) patients developed
      variants of MDS and AL. Monosomia 7 or deletion 7q were diagnosed in 3 cases of
      MDS/AL. In retrospective study of bone marrow specimens of patients with
      transformation in MDS/AL with monosomia 7, FISH recognized a small elevation over
      control values in 2 cases. CONCLUSION: Stable clonal chromosomal aberrations are
      not characteristic of AA. Some AA patients with subsequent MDS/AL may have minor
      neoplastic clone in the disease onset.

PMID- 16944749
TI  - [First experience with the modified program NHL-BFM-90 application in adult
      patients with primary diffuse large B-cell gastric lymphosarcoma with
      unfavourable prognosis].
AB  - AIM: To assess efficacy of a modified program NHL-BFM-90 in adult patients with
      primary diffuse large B-cell gastric lymphosarcoms (PDLBGL) with unfavourable
      prognosis. MATERIAL AND METHODS: Modified courses of NHL-BFM-90 were conducted in
      5 patients aged 27-67 years from January 2004 to September 2005. Four patients
      received chemotherapy of the first line, in one patient block therapy followed
      monotherapy with chlorambucil and a CHOEP course. All the patients were in a
      severe clinical condition and had several initial factors of unfavourable
      prognosis: size of the tumor more than 10 cm; stage IE and more advanced; B
      symptoms; proliferative activity above 70%. The program NHL-BFM-90 was modified
      because of the patients' age. Chemotherapy was conducted according to the middle
      arm of the original program NHL-BFM-90, but methotrexate was introduced in a dose
      1 g/m2 for 12 hours, while leukovorin was given 18 hours after the start of
      methotrexate injection. In two cases the blocks were enhanced with rituximab, 2
      patients had doxorubicin in block A, in one case block C was enhanced with
      methotrexate. A total of 23 modified blocks NHL-BFM-90 were performed: one
      patient was given 6 blocks, two patients--5, one patient--4 blocks and one
      patient--3 blocks. RESULTS: Four patients after block 2 and one patient after
      block 3 of polychemotherapy NHL-BFM-90 achieved remission of the disease of 6 to
      22 months duration which still continues. Infectious complications related to
      hematological toxicity arose more frequently at the latest courses of
      chemotherapy. CONCLUSION: Treatment according to the modified program NHL-BFM-90
      in adult patients with PDLBGL and unfavourable prognosis is highly effective. For
      a mean follow-up of 10.2 months no recurrences occurred. The number of courses
      can be reduced to decrease accumulated hematological toxicity and in case of
      rapid achievement of remission.

PMID- 16944750
TI  - [Flow fluorimetry in differential diagnosis of diffuse large B-cell lymphoma].
AB  - AIM: To analyse immunophenotype of diffuse large B-cell lymphoma (DLBCL) with
      flow cytometry. MATERIAL AND METHODS: Combinations of antibodies against the
      following antigens were used: CD3/ CD19/CD45, CD5/CD19/CD38, CD19/CD10/CD23,
      CD4/CD8/CD3, kappa/lambda/CD19, CD25/CD20/FMC7; CD43/CD22/CD20; CD79a/Ki-67/CD3;
      cytoplasmic kappa/lambda. The analysis was made on flow fluorimeter FacsCalibur
      using computer program CellQuest (Beckton Dickenson, USA). RESULTS: Specific
      coexpression of markers is not detectable in DLBCL, in the greatest degree the
      phenotype corresponds to lymphoma from the cells of the marginal zone. The study
      of cells with maximal direct light diffusion provides more precise assessment of
      clonality and proliferative potential of tumor cells than the analysis of the
      whole lymphocytic polygon. The proliferative index in 33 cases of DLBCL varied in
      the range 10-60%. CONCLUSION: Flow cytometry in most DLBCL cases allows
      identification of B-cell clonality, more precise assessment of a proliferative
      potential of the tumor.

PMID- 16944751
TI  - [Determination of T-cell clonicity by a T-cell receptor gamma-chain: final data].
AB  - AIM: To test diagnostic efficacy of T-cell clonicity determination by a gamma
      chain of T-cell receptor (TCR). MATERIAL AND METHODS: The examination covered 426
      patients (458 tests). T-cell tumors were detected in 132 patients. The samples
      from 294 patients in whom T-cell tumors were not found were referred to the
      laboratory for a differential diagnosis. Clonicity was determined by gamma-chain
      of TCR in the test for conformation polymorphism of one-chain DNA fragments. All
      the tests were made in one laboratory. RESULTS: Sensitivity of the method, found
      by analysis of different delusions of the cell line Jurkat in selected polyclonal
      CD3+ cells is 10%. The results were of 3 kinds: clonal, doubtful and polyclonal.
      In patients free of T-cell tumors there were 15 (5%), 34 (11%) and 258 (84%)
      false positive, doubtful and true negative results. False positive results were
      most frequent in an acute phase of infectious mononucleosis--in 8 (33%) of 24
      patients. 127 (84%) true positive, 5 (3%) doubtful and 19 (13% 0 false negative
      results were documented in patients with T-cell lymphoma. The occurrence of false
      negative results was the highest in anaplastic CD30+ T-cell lymphomas--in 6 (46%)
      of 13 cases. CONCLUSION: Diagnostic efficacy of the method is 92%, but in 10% the
      result is doubtful. Main reason of false negative results is a small number of
      tumor cells in tissue samples. The main reason of false positive results is
      prevalence of one or some T-cell clones in the presence of immune response caused
      by viruses, autoimmune diseases and, possibly, depletion of bone marrow in
      aplastic syndromes.

PMID- 16944752
TI  - [Cytogenetic disorders in chronic B-cell lymphoid leukemia and their relations
      with clinicobiological features and prognosis of the disease].
AB  - AIM: To study a relationship between cytogenetic disorders, clinicobiological
      characteristics and prognosis in chronic B-cell lymphoid leukemia (B-CLL).
      MATERIAL AND METHODS: Cytogenetic examination of blood, bone marrow and lymph
      node cells from 135 patients (90 males and 45 females aged 23-84 years) with
      chronic B-CLL was made. The patients were followed up from 1 month to 25 years.
      Before the cytogenetic examination specific therapy was not given. B-CLL was
      staged by K. Rai, forms--by A.L. Vorobyev and M.D. Brilliant. All the patients
      have undergone standard cytogenetic examination, FISH with multicolor probe to
      loci with possible frequent aberrations (del3q14, del11q23, del17p13, trisomia
      12), determination of CD38 antigen expression on circulating tumor cells.
      Mutation status of the genes of immunoglobulins variable region (IgVH) was
      defined in 61 patients. RESULTS: Del13q14 was detected in 34 cases, del11q23--in
      26, trisomia of chromosome 12--in 17 cases, del 17p13--in 8, absence of q-arm of
      chromosome 13--in 3 cases. 61 patients had no karyotype defects. Three prognostic
      groups of the patients were identified: favourable prognosis--patients without
      disorders of karyotype and one chromosomal aberration--del13q14; intermediate
      prognosis patients with dell1q23 and trisomia of chromosome 12; poor prognosis-
      patients with del17p13 and complex disorders of karyotype. CONCLUSION.
      Cytogenetic study help determine prognosis of B-CLL and detect patients in need
      of early therapy.

PMID- 16944753
TI  - [Outpatient hospital technologies in hematology].
AB  - AIM: To study possibilities of cure of hemoblastosis patients in the setting of
      day hospital (DH). MATERIAL AND METHODS: The experience with 5-year activity of
      the first in Russia hematological DH is analyzed. Managerial, clinical, economic
      and social aspects of DH activity are considered. RESULTS: Basing on the
      experience of the DH activity, indications for hospitalization of patients with
      hematological malignancy (HM) to DH, the model of management of hematological DH,
      the diseases which can be treated in hematological DH are specified. Cost-effect
      efficacy of establishment of hematological day hospitals is validated.
      CONCLUSION: Hematological DH is a modern, cost effective form of rendering
      special medical assistance in outpatient setting providing examination and
      treatment of hematological patients without loss of quality of diagnosis,
      treatment and life.

PMID- 16944754
TI  - [Effect of cytarabine on expression of cell adhesion molecules and on endothelium
      leukocyte interaction in vitro].
AB  - AIM: To characterize cytarabine effects on human endothelium expression of cell
      adhesion molecules (CAM) of various classes and interaction of cultured
      endothelial cells (EC) with blood leukocytes. MATERIAL AND METHODS: Primary
      cultures of EC of human umbilical vein were obtained by EC culturing for 24-72 h
      with cytarabine (10 mcg/ml). They were investigated with phase-contrast
      microscopy, immunohistochemistry and flow cytometry. RESULTS: Cytarabine effects
      manifested with EC-induced expression of cell surface P- and E-selectines and
      VCAM-1; ICAM-1 expression rapidly enhanced, leukocyte adhesion to endothelium
      also activates. CONCLUSION: Cytarabine, as a pathogenetic factor, induces
      proinflammatory alterations of the endothelium responsible for development of
      vascular complications in patients on cytostatic therapy.

PMID- 16944755
TI  - [Effect of parathyroid hormone (PTH 1-34) on hemopoiesis in long-term cultures of
      human bone marrow].
AB  - AIM: To study effects of parathyroid hormone (PTH) used in therapy of
      osteoporosis on hemopoiesis in long-term culture of human bone marrow (LCBM) in
      terms of its potential influence on stem hemopoietic and stromal cells. MATERIAL
      AND METHODS: For a long time LCBM was treated with PTH (1-34) and compared for
      cell production, concentration of late and early hemopoietic precursors.
      Maintenance of hemopoiesis and adhesion at early hemopoiesis precursors on the
      stromal sublayers treated with PTH (1-34) was used as a functional test. A
      relative level of expression of genes participating in regulating proliferation
      and self-support of stem hemopoietic cells was studied. RESULTS: PTH (1-34) in
      the above concentrations did not affect hemopoiesis in LCBM. Stromal sublayer
      treated with PTH (1-34) for a long time supports cell precursors better, their
      adhesion to such sublayers enhances. CONCLUSION: PTH (1-34) in pharmacological
      but small concentrations had no irreversible effects on hemopoiesis, i.e.
      contraindications for its use in the treatment of osteoporosis were not revealed.

PMID- 16944756
TI  - [Diffuse large B-cell lymphosarcoma: difficulties and errors of diagnosis].

PMID- 16944757
TI  - [Combination of chronic lymphoid leukemia and hairy cell leukemia].

PMID- 16944758
TI  - [Remission in T-cell prolymphocytic leukemia during the FMC treatment course].

PMID- 16944759
TI  - [Hemodilution and hemodilution coagulopathy].

PMID- 16944760
TI  - [Composition of populations and clones of lymphocytes in cytopenic conditions of
      hemopoiesis].

PMID- 16944761
TI  - [Massive tumor cytolysis syndrome].

PMID- 16944762
TI  - Rapid HIV testing for managing occupational exposures.

PMID- 16944763
TI  - When medicine and culture collide.

PMID- 16944764
TI  - Welcome back to school!

PMID- 16944765
TI  - Retention of medical records--guideposts to consider.

PMID- 16944766
TI  - Political forecasting heats up.

PMID- 16944768
TI  - Which is better: lease or buy?

PMID- 16944767
TI  - Health literacy: are you doing enough to communicate with your patients?

PMID- 16944769
TI  - Student debt: an unsustainable problem.

PMID- 16944770
TI  - Numerical simulation of microcarrier motion in a rotating wall vessel bioreactor.
AB  - OBJECTIVE: To analyze the forces of rotational wall vessel (RWV) bioreactor on
      small tissue pieces or microcarrier particles and to determine the tracks of
      microcarrier particles in RWV bioreactor. METHODS: The motion of the microcarrier
      in the rotating wall vessel (RWV) bioreactor with both the inner and outer
      cylinders rotating was modeled by numerical simulation. RESULTS: The continuous
      trajectory of microcarrier particles, including the possible collision with the
      wall was obtained. An expression between the minimum rotational speed difference
      of the inner and outer cylinders and the microcarrier particle or aggregate
      radius could avoid collisions with either wall. The range of microcarrier radius
      or tissue size, which could be safely cultured in the RWV bioreactor, in terms of
      shear stress level, was determined. CONCLUSION: The model works well in
      describing the trajectory of a heavier microcarrier particle in rotating wall
      vessel.

PMID- 16944771
TI  - In vitro anti-HIV activity of a Chinese fungus extract.
AB  - OBJECTIVE: To investigate the inhibitory effect of the mycelium extract from a
      Chinese fungus (M1) on HIV-1 and its mode of action. METHODS: Several in vitro
      methods including time of action, time of addition and PCR were used to test the
      mode of action of M1. RESULTS: M1 inhibited acute HIV infection in vitro and was
      effective when it was added 12 h after infection. PCR analysis of infected cells
      demonstrated that M1 delayed the appearance of late product of reverse
      transcription and HIV was blocked before its RNA expression. CONCLUSION: The
      target of M1 is post-integration of proviral DNA.

PMID- 16944772
TI  - Waste water disinfection during SARS epidemic for microbiological and
      toxicological control.
AB  - OBJECTIVE: To evaluate the disinfection of wastewater in China. METHODS: During
      the SARS epidemic occurred in Beijing, a study of different disinfection methods
      used in the main local wastewater plants including means of chlorine, chlorine
      dioxide, ozone, and ultraviolet was carried out in our laboratory. The residual
      coliform, bacteria and trihalomethanes, haloacetic acids were determined after
      disinfection. RESULTS: Chlorine had fairly better efficiency on microorganism
      inactivation than chlorine dioxide with the same dosage. Formation of THMs and
      HAAs does not exceed the drinking water standard. UV irradiation had good
      efficiency on microorganism inactivation and good future of application in China.
      Organic material and ammonia nitrogen was found to be significant on inactivation
      and DBPs formation. CONCLUSION: Chlorine disinfection seems to be the best
      available technology for coliform and bacteria inactivation. And it is of fairly
      low toxicological hazard due to the transformation of monochloramine.

PMID- 16944773
TI  - Common SNPs of APM1 gene are not associated with hypertension or obesity in
      Chinese population.
AB  - OBJECTIVE: To investigate whether the common variants 45T/G and 276G/T in APM1
      gene were associated with hypertension combined with obesity (HO) and related
      clinical features in Chinese Han population. METHODS: A case-control study design
      was applied. Common polymorphisms of 45T/G and 276G/T were genotyped by PCR
      product sequencing in 484 cases with HO and 502 controls with normal blood
      presure and BMI < 25. RESULTS: The genotype and allele frequencies of 45T/G,
      276G/T, and haplotype defined by the two variants in cases did not differ from
      those in controls. The means of blood pressure, BMI and waist-hip ratio did not
      differ among genotypes of the two polymorphisms and haplotypes. Among lipid
      profiles, only serum high-density lipoprotein cholesterol (HDL-C) levels were
      significantly lower in T allele carriers than that in non-T carriers after
      adjusting possible confounding factors (1.21 vs 1.32 mmol/L, P=0.0001).
      CONCLUSION: Polymorphisms of 45T/G and 276G/T in APM1 gene are not associated
      with hypertension or obesity, or their clinical features in Chinese Han
      population. Common polymorphism of 45T/G might be associated with serum HDL-C
      levels in Chinese.

PMID- 16944774
TI  - Inhibitory effects of saponins from Anemarrhena asphodeloides Bunge on the growth
      of vascular smooth muscle cells.
AB  - OBJECTIVE: To investigate the effects of saponins from Anemarrhena asphodeloides
      Bunge (SAaB) (Botanical Name: Anemarrhena Asphodeloidis Rhizoma) on the growth of
      vascular smooth muscle cells (VSMCs). METHODS: Cell proliferation was measured by
      a newly developed cell proliferation reagent, WST-1. Cell apoptosis was assayed
      by flow cytometry through detecting annexin V. Nitric oxide production was
      evaluated using confocal laser scanning microscopy with diaminofluorescein
      diacetate (DAF-2, DA). Cell aldose reductase (AR) activity, as well as the effect
      of Epalrestat and interleukin-1beta were also explored. RESULTS: WST assay showed
      that cell proliferation induced by serum was significantly inhibited by SAaB
      (P<0.01). Flow cytometry analysis revealed that SAaB could enhance apoptotic rate
      of VSMCs (P<0.01). Nitric oxide production was significantly enhanced after
      administration of SAaB and interleukin-1beta. Moreover, AR activity of VSMCs was
      also remarkably inhibited by both SAaB and Epalrestat (P<0.01). CONCLUSION: SAaB
      can inhibit proliferation and enhance apoptosis of VSMCs. It may protect vascular
      cells by inhibiting VSMC proliferation and augmenting apoptotic rate of VSMCs via
      NO-dependent pathway.

PMID- 16944775
TI  - Influence of chemical oxygen demand concentrations on anaerobic ammonium
      oxidation by granular sludge from EGSB reactor.
AB  - OBJECTIVE: To investigate the effect of chemical oxygen demand (COD)
      concentrations on the anaerobic ammonium oxidation (ANAMMOX). METHODS: An
      Expanded Granular Sludge Bed (EGSB) reactor was used to cultivate the granular
      sludge and to perform the ANAMMOX reaction in the bench scale experiment. NH4(+)
      N and NO2(-)-N were measured by using colorimetric method. NO3(-)-N was analyzed
      by using the UV spectrophotometric method. COD measurement was based on digestion
      with potassium dichromate in concentrated sulphuric acid. RESULTS: When the COD
      concentrations in the reactors were 0 mg/L, 200 mg/L, 350 mg/L, and 550 mg/L,
      respectively, the NH4(+)-N removal efficiency was 12.5%, 14.2%, 14.3%, and 23.7%;
      the removal amount of NO2(-)-N was almost the same; the nitrate removal
      efficiency was 16.8%, 94.5%, 86.6%, and 84.2% and TN removal efficiency was
      16.3%, 50.7%, 46.9%, and 50.4%, moreover, the COD removal efficiency was 85%,
      65.7%, and 60%; the COD removal rate was 27.42, 61.88, and 97.8 mg COD/(h x L).
      CONCLUSION: COD concentrations have a significant influence on anaerobic ammonium
      oxidation by granular sludge.

PMID- 16944776
TI  - DNA damage, apoptosis and C-myc, C-fos, and C-jun overexpression induced by
      selenium in rat hepatocytes.
AB  - OBJECTIVE: To study the effects of selenium on DNA damage, apoptosis and c-myc, c
      fos, and c-jun expression in rat hepatocytes. METHODS: Sodium selenite at the
      doses of 5, 10, and 20 micromol/kg was given to rats by i.p. and there were 5
      male SD rats in each group. Hepatocellular DNA damage was detected by single cell
      gel electrophoresis (or comet assay). Hepatocellular apoptosis was determined by
      TUNEL (TdT-mediated dUTP nick end labelling) and flow cytometry. C-myc, c-fos,
      and c-jun expression in rat hepatocytes were assayed by Northern dot
      hybridization. C-myc, c-fos, and c-jun protein were detected by
      immunohistochemical method. RESULTS: At the doses of 5, 10, and 20 micromol/kg,
      DNA damage was induced by sodium selenite in rat hepatocytes and the rates of
      comet cells were 34.40%, 74.80%, and 91.40% respectively. Results also showed an
      obvious dose-response relationship between the rates of comet cells and the doses
      of sodium selenite (r=0.9501, P<0.01). Sodium selenite at the doses of 5, 10, and
      20 micromol/kg caused c-myc, c-fos, and c-jun overexpression obviously. The
      positive brown-yellow signal for proteins of c-myc, c-fos, and c-jun was mainly
      located in the cytoplasm of hepatocytes with immunohistochemical method. TUNEL
      positive cells were detected in selenium-treated rat livers. Apoptotic rates (%)
      of selenium-treated liver cells at the doses of 5, 10, and 20 micromol/kg were
      (3.72 +/- 1.76), (5.82 +/- 1.42), and (11.76 +/- 1.87) respectively, being much
      higher than those in the control. Besides an obvious dose-response relationship
      between apoptotic rates and the doses of sodium selenite (r=0.9897, P<0.01),
      these results displayed a close relationship between DNA damage rates and
      apoptotic rates, and the relative coefficient was 0.9021, P<0.01. CONCLUSION:
      Selenium at 5-20 micromol/kg can induce DNA damage, apoptosis, and overexpression
      of c-myc, c-fos, and c-jun in rat hepatocytes.

PMID- 16944777
TI  - Phthalate exposure and human semen quality in Shanghai: a cross-sectional study.
AB  - OBJECTIVE: To monitor the level of phthalates in human semen samples and to
      analyze the relationship between phthalate levels and semen parameters. METHODS:
      Concentrations of three kinds of commonly used phthalates (di-ethyl phthalate,
      DEP; di-n-butyl phthalate, DBP; di-2-ethylhexyl phthalate, DEHP) were measured
      using reversed-phase HPLC. Semen parameters were measured by computer aided sperm
      analysis (CASA). RESULTS: The three phthalates were detected in most of the
      biological samples, with median levels of 0.30 mg/L (0.08-1.32 mg/L) in semen
      specimens. There was a significant positive association between liquefied time of
      semen and phthalate concentrations of semen. The correlation coefficient was
      0.456 for DEP, 0.475 for DBP, and 0.457 for DEHP, respectively. There was no
      significant difference between phthalate concentrations of semen and sperm
      density or livability, though the correlation coefficients were negative.
      CONCLUSION: These results suggest that people who reside in Shanghai are exposed
      to phthalates, especially to DBP and DEHP. Although the level of phthalates is
      relatively mild, an association of phthalate levels and reduced quality of human
      semen has been shown in the present study.

PMID- 16944778
TI  - Immediate-early inducible function in upstream region of junB gene.
AB  - OBJECTIVE: To analyze the upstream region of radiation-induced junB gene.
      METHODS: Four plasmids containing 250 bp, 590 bp, 900 bp and 1650 bp, and CAT
      reporter gene were constructed separately and introduced to L8704 cells. The
      cells were irradiated with 2 Gy X-rays and incubated at different intervals.
      Total RNA was extracted from the cells and fluctuation of the CAT mRNA level was
      assessed by the RNA ratio of CAT/beta-actin measured by quantitative Northern
      blot hybridization. RESULTS: CAT mRNA expression containing 900 bp and 1560 bp
      junB promoter remarkably and rapidly increased, and reached its peak 30 min after
      2 Gy X-ray irradiation. CONCLUSIONS: 590-900 bp fragments located in the upstream
      region of junB gene play an important role in the early process of cells against
      radiation.

PMID- 16944779
TI  - Establishment of cell free conversion system with biotin-labelled recombinant
      PrPsen expressed in E. coli.
AB  - OBJECTIVE: To report a protocol using biotin-labelled PrP protein in cell free
      conversion assay instead of isotope. METHODS: A hamster PrP protein (HaPrP) was
      expressed in E. coli and purified with HIS-tag affinity chromatograph. After
      being labelled with biotin, HaPrP was mixed with PrPSc preparation from scrapie
      strain 263K. RESULTS: Protease-resistant bands were detected after four-day
      incubation. CONCLUSION: The new conversion model provides a reliable, easily
      handling, and environment-friendly method for studies of prion and transmissible
      spongiform encephalopathies.

PMID- 16944781
TI  - Identification and determination of microcystins in source water and waterbloom
      sample from Meiliang Bay, Taihu Lake, China.
AB  - OBJECTIVE: To identify and determine the congener and level of microcystins in
      the source water of Taihu Lake. METHODS: Improved method of SPE combined with
      HPLC was employed to detect the concentration and varieties of microcystins in
      source water and bloom samples collected from Meiliang Bay, Taihu Lake. RESULTS:
      The contents of two predominant microcystin components, MC-RR, and MC-LR, were
      relatively high in samples during warm months and correlated with the phase of
      algae growth. The maximum concentrations of MC-RR and MC-LR in water sample
      reached 3.09 +/- 0.53 microg/L and 2.39 +/- 0.41 microg/L during the period of
      water bloom in September 2004, respectively. Even without waterbloom, the
      concentration of MC-LR in source water sample was still higher than the guideline
      value. CONCLUSION: The status of microcystin pollution in this region is serious
      and measures to monitor and control the growth of cyanobacteria are urgently
      needed.

PMID- 16944780
TI  - Synergistic effect of schwann cells and retinoic acid on differentiation and
      synaptogenesis of hippocampal neural stem cells in vitro.
AB  - OBJECTIVE: To investigate the synergistic effect of Schwann cells (SCs) and
      retinoic acid (RA) on differentiation and synaptogenesis of neural stem cells
      (NSCs) derived from hippocampus of neonatal rats. METHODS: The classical method
      for 2x2 factorial analysis experiment was used to assess synergistic action of
      SCs and RA. NSCs were treated with RA, SCs, and SCs + RA in DMEM/F12 with 0.5%
      fetal bovine serum for six days, respectively. Double immunofluorescent staining
      was used to detect the differentiation of NSCs including nestin, glial fibrillary
      acidic protein (GFAP) and Map2. The expression of PSD95 was used to demonstrate
      synaptogenesis. RESULTS: After NSCs were treated with RA or SCs, the expression
      of nestin and GFAP was significantly decreased while the expression of Map2 and
      PSD95 was significantly increased in comparison with the control. Factorial ANOVA
      showed that interactions between SCs and RA could induce the expression of Map2
      and PSD95. CONCLUSION: SCs and RA could promote synergistically the neuronal
      differentiation and synaptogenesis of hippocampal neural stem cells in vitro
      while they decreased the astrocytes and nestin positive NSCs.

PMID- 16944782
TI  - Association between polymorphisms of DNA repair gene XRCC1 and DNA damage in
      asbestos-exposed workers.
AB  - OBJECTIVE: To compare the asbestos-induced DNA damage and repair capacities of
      DNA damage between 104 asbestos-exposed workers and 101 control workers in
      Qingdao City of China and to investigate the possible association between
      polymorphisms in codon 399 of XRCC1 and susceptibility to asbestosis. METHODS:
      DNA damage levels in peripheral blood lymphocytes were determined by comet assay,
      and XRCC1 genetic polymorphisms of DNA samples from 51 asbestosis cases and 53
      non-asbestosis workers with a similar asbestos exposure history were analyzed by
      PCR/RFLP. RESULTS: The basal comet scores (3.95 +/- 2.95) were significantly
      higher in asbestos-exposed workers than in control workers (0.10 +/- 0.28). After
      1 h H2O2 stimulation, DNA damage of lymphocytes exhibited different increases.
      After a 4 h repair period, the comet scores were 50.98 +/- 19.53 in asbestos
      exposed workers and 18.32 +/- 12.04 in controls. The residual DNA damage (RD) was
      significantly greater (P<0.01) in asbestos-exposed workers (35.62%) than in
      controls (27.75%). XRCC1 genetic polymorphism in 104 asbestos-exposed workers was
      not associated with increased risk of asbestosis. But compared with polymorphisms
      in the DNA repair gene XRCC1 (polymorphisms in codon 399) and the DNA damage
      induced by asbestos, the comet scores in asbestosis cases with Gln/Gln, Gln/Arg,
      and Arg/Arg were 40.26 +/- 18.94, 38.03 +/- 28.22, and 32.01 +/- 11.65,
      respectively, which were higher than those in non-asbestosis workers with the
      same genotypes (25.58 +/- 11.08, 37.08 +/- 14.74, and 29.38 +/- 10.15). There
      were significant differences in the comet scores between asbestosis cases and non
      asbestosis workers with Gln/Gln by Student's t-test (P<0.05 or 0.01). The comet
      scores were higher in asbestosis workers with Gln/Gln than in those with Arg/Arg
      and in non-asbestosis workers exposed to asbestos, but without statistically
      significant difference. CONCLUSIONS: Exposure to asbestos may be related to DNA
      damage or the capacity of cells to repair H2O2-induced DNA damage. DNA repair
      gene XRCC1 codon 399 may be responsible for the inter-individual susceptibility
      in DNA damage and repair capacities.

PMID- 16944783
TI  - Vitamin C inhibits benzo[a]pyrene-induced cell cycle changes partly via cyclin
      D1/E2F pathway in human embryo lung fibroblasts.
AB  - OBJECTIVE: To study the molecular mechanism of the inhibitory effects of vitamin
      C on benzo[a]pyrene (B[a]P)-induced changes of cell cycle in human embryo lung
      fibroblast (HELF) cells. METHODS: The stable transfectants, HELF transfected with
      antisense cyclin D1 and antisense CDK4, were established. Cells were cultured and
      pretreated with vitamin C before stimulation with B[a]P for 24 h. The expression
      levels of cyclin D1, CDK4, E2F1, and E2F4 were determined by Western blot. Flow
      cytometric analysis was employed to detect the distributions of cell cycle.
      RESULTS: B[a]P significantly elevated the expression levels of cyclin D1, E2F1,
      and E2F4 in HELF cells. Vitamin C decreased the expression levels of cyclin D1,
      E2F1, and E2F4 in B[a]P-stimulated HELF cells. Dose-dependent relationships were
      not found between the different concentrations of vitamin C (10, 100, 500, 1000,
      and 5000 micromol/L) and the expression levels of cyclin D1, E2F1, and E2F4 in
      HELF cells. The expression levels of cyclin D1, E2F1, and E2F4 in B[a]P-treated
      transfectants were lower than those in B[a]P-treated HELF cells. The expression
      levels of cyclin D1 and E2F4 treated with vitamin C and antisense cyclin D1 were
      decreased compared with those treated with antisense cyclin D1 alone. The effects
      of vitamin C combined with antisense CDK4 on the expression levels of cyclin D1
      and E2F1/E2F4 were similar to those of antisense CDK4 alone. B[a]P progressed
      HELF cells from G1 to S phase. Both vitamin C and antisense cyclin D1 suppressed
      the changes of cell cycle progressed by B[a]P. However, antisense CDK4 did not
      attenuate the above changes. Vitamin C combined with antisense CDK4 markedly
      suppressed B[a]P-induced changes of cell cycle as compared with antisense CDK4.
      But the inhibitory effects of vitamin C combined with antisense cyclin D1 on
      B[a]P-induced changes of cell cycle were similar to those of vitamin C alone or
      antisense cyclin D1 alone. CONCLUSIONS: B[a]P progressed HELF cells from G1 to S
      phase via intracellular signaling pathway of cyclin D1/E2F. Vitamin C may
      modulate this signaling pathway to protect cells from injury caused by B[a]P.

PMID- 16944785
TI  - Palliative care gains support in medical community.

PMID- 16944784
TI  - Price packaging and transparency: get ready for government mandates, consumer
      demand.

PMID- 16944786
TI  - Hospitals improve communication, efficiency, and patient safety with hands-free
      WiFi device.

PMID- 16944787
TI  - Internal affairs: current problematic issues in Critical Incident Stress
      Management for emergency services.
AB  - Critical Incident Stress Management is really in it's infancy as a valid crisis
      intervention technique. With that in mind, everyone involved--peers, mental
      health professionals, pastoral counselors, trainers, and academicians--must
      support the CISM model by knowing it thoroughly, conducting it appropriately,
      taking care of themselves and their fellow team members, continuing to be trained
      and educated, and promoting cohesive teams that thrive through their ongoing
      work.

PMID- 16944788
TI  - Past violence, substance use, and precipitants to psychiatric patient assaults:
      eleven-year analysis of the Assaulted Staff Action Program (ASAP).
AB  - Thirty-five years of empirical research on assaultive psychiatric patients has
      documented the presence of consistent patient assailant characteristics. However,
      these characteristics studies have yielded little in the way of predictor
      variables. This study examined three commonly present, patient clinical variables
      (past violence toward others, personal victimization, and substance use disorder)
      singly and in combinations as potential predictor variables. An additional subset
      analysis of patient precipitants was added to ascertain whether precipitant data
      would add further predictive power The combinations of past violence toward
      others and personal victimization with and without substances use disorder during
      an eleven-year period were associated with 61% of the subsequent assaults. A
      trend for denial of services to female patients during a three-year period was
      also associated with subsequent assaults. The predictive implications of these
      findings and their relevance for emergency services personnel are examined.

PMID- 16944789
TI  - Suicide by cop: causes, reactions, and practical intervention strategies.
AB  - Due to a combination of interpersonal manipulativeness, personal identification,
      and lack of heroic status, most police officers find suicide by cop (SBC) calls
      to be among the most disturbing shooting incidents. This article describes the
      dynamics of SBC and some of the factors that may contribute to it. Operational
      strategies and psychological techniques for de-escalating and resolving a SBC
      crisis are discussed. Finally, psychological reactions by officers to a SBC and
      psychotherapeutic strategies for dealing with the aftermath are described.
      Especially important is the recommendation that officers use intervention
      "failures" as tools for learning, so that purposeless remorse can be turned into
      enhanced life-saving skills for the next incident.

PMID- 16944790
TI  - Applying Roberts' Triple ABCD Model in the aftermath of crisis-inducing and
      trauma-inducing community disasters.
AB  - Natural and man-made community disasters, such as hurricanes, earthquakes, school
      shootings, and mass terrorist attacks, heavily impact the safety, mental health,
      and well-being of large numbers of individuals, families and groups. Millions of
      individuals who experience acute crisis episodes or psychological trauma are not
      consistently provided with the early psychological interventions they urgently
      need. There is a critical need for tools and a framework to quickly and
      effectively promote interventions. This article presents one such effort, the
      Roberts' Triple ABCD Model. This model is an up-to-date and integrated conceptual
      framework that helps to provide the foundation for developing a unified standard
      of care for crisis and disaster mental health interventions. This model can be
      useful in determining which early intervention methods and techniques are most
      likely to reduce traumatic stress, treat acute crisis and psychosocial symptoms,
      and promote recovery.

PMID- 16944791
TI  - College crisis intervention: an initiative to develop regional campus Critical
      Incident Stress Management teams.
AB  - This article presents a statewide initiative that was undertaken to develop
      regional Critical Incident Stress Management (CISM) teams among colleges and
      universities within a northeastern state. In light of the unique needs and
      culture of institutions of higher education, this initiative was intended to
      improve each member college or university's capacity to respond comprehensively
      and effectively to critical incidents that affect its community. A step-by-step
      description of the implementation of the initiative is presented as well as
      discussion of what was learned through the process and future directions.

PMID- 16944792
TI  - Critical incident stress debriefing for law enforcement: practical models and
      special applications.
AB  - Critical incident stress debriefing (CISD) has evolved and diversified to address
      the needs of various subpopulations of public safety and emergency services
      personnel, including law enforcement. This article describes the concept of
      critical incident stress as it applies to police officers and other law
      enforcement agents. It then discusses the traditional debriefing models and the
      specialized modifications and applications that have been introduced to deal with
      the needs of law enforcement individuals and groups. Next, the role of peer
      debriefing is described in addressing law enforcement critical incident stress,
      as well as specific examples of model programs within different types of law
      enforcement agencies. Finally, the as yet incompletely resolved legal and
      administrative issues surrounding the use of peers versus professional clinicians
      for critical incident intervention are addressed.

PMID- 16944793
TI  - Communicating bad news: a model for emergency mental health helpers.
AB  - This article addresses the concerns of the messenger/helper who must convey
      tragic news to individuals and families. It offers a model to be used as a guide
      to ease the stress on both the deliverer and receiver of bad news. The model uses
      the mnemonic, PEWTER (Prepare, Evaluate, Warn, Tell, Emotional Response,
      Regroup), to represent the six components of the communication process.

PMID- 16944794
TI  - We need to get evacuations right.

PMID- 16944795
TI  - We had a great AIHce this year.

PMID- 16944797
TI  - All along the watchtowers.

PMID- 16944796
TI  - Employees improve with age.

PMID- 16944798
TI  - Screening can cut down on liabilities.

PMID- 16944799
TI  - Why drugs and safety don't mix.

PMID- 16944800
TI  - Facing unexpected hazards.

PMID- 16944801
TI  - Misinformation and the ANSI standard.

PMID- 16944802
TI  - Standpipe fire hose stations save lives, protect property.

PMID- 16944803
TI  - Protecting employees in volatile industrial surroundings.

PMID- 16944804
TI  - ISEA vs. ISO: apparel standards examined.

PMID- 16944805
TI  - Predicting the unpredictable: PPE planning for a natural disaster.

PMID- 16944806
TI  - How to assess machine risks.

PMID- 16944807
TI  - [The study of cholinesterases of different origins by method oh inhibitory
      analysis (variation of phosphoryl group of alcoxyalcylphosphonates].

PMID- 16944808
TI  - [Comparative study of blood plasma lipids and fatty acids in lamprey Lampetra
      fluviatilis and frog Rana temporaria during food deprivation].

PMID- 16944809
TI  - [pH influences on somatotropin binding activity of theca and granulosa tissues in
      preovulating follicules in chicken].

PMID- 16944810
TI  - [Areal influence on functional activity of liver mitochondria of two small
      mammalian species with different ecological specialisation].

PMID- 16944811
TI  - [Molecular mechanisms of polycation peptides interaction with serpentine type
      receptors and heterotrimeric g-proteins in rat tissue].

PMID- 16944812
TI  - [Comparative study of cholinergic activity of troponol and isoquinoline
      alkaloids].

PMID- 16944813
TI  - [Ryanodine does not show negative chronotropic effect on action potentials
      generation in pacemaking cells of heart of young frogs Rana Temporaria. ].

PMID- 16944814
TI  - [Brain cortex oxygen supply in acute nitrite hypoxia in rodents with different
      ecological specialisation].

PMID- 16944815
TI  - [Studies of ECG, parameters of external breathing and motor activity of rats of
      different ages during acute fluoroacetamide intoxication].

PMID- 16944816
TI  - [Development of cardio-motor relationships during rat ontogenesis].

PMID- 16944817
TI  - [Influence of phloretin and phloridzin on digestive and adsorptive
      characteristics of rat small intestine].

PMID- 16944818
TI  - [Hypoxic factors influence on chronotropic heart reactions of ondatra Ondatra
      zibethicus in free behavior].

PMID- 16944819
TI  - [Nitroxidergetic elements in digestive system of Mactra chinensis and Spisula
      sachalinensis (mollusca: Bivalvia: Mactridae)].

PMID- 16944820
TI  - [Ventrothalamic region organisation of sturgeon fishes].

PMID- 16944821
TI  - [Comparative study of proton- and calcium-dependent uncoupling action of
      palmitate in liver mitochondria of adult and aged guinea pigs Cavia porcellus].

PMID- 16944822
TI  - The effect of exercise of the affected foot in stroke patients--a randomized
      controlled pilot trial.
AB  - OBJECTIVE: To evaluate the effect of treatment with a portable device called
      Stimulo on range of motion, muscle strength and spasticity in the ankle joint and
      its effect on walking ability, balance, activities of daily living (ADL) and
      health-related quality of life in stroke patients. DESIGN: A randomized
      controlled pilot study. SETTING: A research centre. SUBJECTS: Ambulatory or
      partly ambulatory chronic stroke patients with remaining spasticity and/or
      decreased range of motion in the hemiparetic leg/ankle. INTERVENTIONS:
      Standardized and individualized programme including active and passive range of
      motion of the ankle with a portable device (Stimulo), performed three times a
      week for 30 min, over a six-week period. MAIN MEASURES: Range of motion, muscle
      strength, spasticity, gait variables, balance, ADL and health-related quality of
      life. RESULTS: Eighteen subjects were included in the study with a mean age of 75
      years. The compliance rate was 94-99%. There were no significant differences
      between the groups. CONCLUSION: The study showed no significant effect of an
      ankle-exercise intervention programme with Stimulo. Further studies with a larger
      sample size are of importance before any further conclusions can be drawn.

PMID- 16944823
TI  - Contracture preventive positioning of the hemiplegic arm in subacute stroke
      patients: a pilot randomized controlled trial.
AB  - OBJECTIVE: To investigate the effectiveness of a contracture preventive
      positioning procedure for the hemiplegic arm in subacute stroke patients in
      addition to conventional physio- and occupational therapy. DESIGN: A single-blind
      pilot randomized controlled trial. SETTING: Inpatient neurological units from
      three rehabilitation centres in the Netherlands. SUBJECTS: Nineteen subacute
      stroke patients (minus two drop-outs) with a severe motor deficit of the arm.
      INTERVENTIONS: All subjects underwent conventional rehabilitation care. Nine
      subjects additionally received a positioning procedure for two 30-min sessions a
      day, five days a week, for five weeks. MAIN MEASURES: Passive range of motion of
      five arm movements using a hydrogoniometer and resistance to passive movement at
      the elbow using the Ashworth Scale. Secondary outcome measures were pain at the
      end range of passive motions, the arm section of the Fugl-Meyer Assessment and
      Barthel Index scores for ADL-independence. Outcome measures were taken after five
      weeks and additional measurements after 10 weeks by two assessors blinded to
      group allocation. RESULTS: Comparison of the experimental (n = 9) with the
      control subjects (n = 8) after five weeks showed that additional positioning
      significantly slowed down development of shoulder abduction contracture (P =
      0.042, -5.3 degrees versus -23 degrees). No other differences were found between
      the groups. CONCLUSIONS: Applying a contracture preventive positioning procedure
      for the hemiplegic arm slowed down the development of shoulder abduction
      contracture. Positioning did not show significant additional value on other
      outcome measures. Since the sample size was small, results of this study need
      future verification.

PMID- 16944824
TI  - The effect of botulinum toxin type A injection into the gastrocnemius muscle on
      sit-to-stand transfer in children with spastic diplegic cerebral palsy.
AB  - OBJECTIVE: To investigate the benefit of botulinum toxin type A injection into
      the ankle plantarflexor muscle on sit-to-stand transfer in children with spastic
      diplegic cerebral palsy. DESIGN: Case-control study. SETTING: Inpatients in a
      university-affiliated hospital. SUBJECTS: Forty spastic diplegic children aged
      from 2 to 6 years (18 children with botulinum toxin type A injection into both
      gastrocnemius muscles as an experimental group and 14 children without injection
      as a control group). MAIN MEASURES: Sit-to-stand transfer task was evaluated
      using a motion analyser (Vicon 370 MA with six infrared cameras). The tests were
      performed twice with a two- week interval. The changes in temporal, kinematic and
      kinetic parameters were investigated in each group. RESULTS: In the control group
      there were no significant changes in any of the measured parameters between the
      tests. In the experimental group, total duration (s) of sit-to-stand transfer was
      shortened after injection (4.35 +/- 2.49 to 2.89 +/- 1.48, P < 0.05). The maximal
      angles (degrees) of pelvic and hip joints were reduced (28.88 +/- 5.53 to 26.57
      +/- 3.73 and 90.78+8.69 to 87.23 +/- 8.76) and the initial angle of ankle
      dorsiflexion was increased (4.41 +/- 6.16 to 7.08 +/- 6.09) after injection (P <
      0.05). The maximal moments (Nm/kg) of the hip and knee joints (0.44 +/- 0.17 to
      0.51 +/- 0.21 and 0.13 +/- 0.05 to 0.18 +/- 0.14) were increased while that of
      the ankle joint was reduced (0.32 +/- 0.09 to 0.28 +/- 0.10) after injection (P <
      0.05). Only the cases with greater reduction of spasticity showed an improvement
      on kinematic and kinetic parameters. CONCLUSION: Botulinum toxin type A injection
      into spastic ankle plantarflexors led to better accomplishment of sit-to-stand
      transfer in children with spastic diplegic cerebral palsy.

PMID- 16944825
TI  - Comparison of customized versus standard exercises in rehabilitation of shoulder
      disorders.
AB  - OBJECTIVE(S): (1) To compare the effectiveness of customized exercises with that
      of standard exercises for the treatment of patients with shoulder disorders. (2)
      To determine whether four weeks or eight weeks would be needed to see improvement
      in outcome measures. DESIGN: A single-blinded randomized clinical trial. SETTING:
      An outpatient physical therapy clinic affiliated with an academic institution.
      SUBJECTS: Thirty patients with shoulder disorders were tested and treated between
      February 2003 and December 2004. INTERVENTIONS: Patients were randomized to a
      customized or standard exercise group. Each patient first underwent a
      standardized physical therapy assessment. Based on the results of the assessment,
      a classification was determined and a classification-specific exercise programme
      was instructed to the patients in the customized exercise group. The standard
      exercise group, regardless of classification, received preselected standard
      exercises. Both groups were followed for eight weeks. MAIN MEASURES: Shoulder
      range of motion, strength, pain intensity and function were assessed three times
      (weeks 0, 4 and 8). RESULTS: There were no significant differences between the
      customized and standard exercise groups in measures of shoulder range of motion,
      strength, pain intensity and function after four or eight weeks of exercise.
      Patients in both groups had significant improvements in shoulder strength, pain
      intensity and function. Significant improvements occurred at week 8, but not at
      week 4. CONCLUSION: The customized shoulder exercises did not provide additional
      benefit to our shoulder patients than the standard exercises.

PMID- 16944826
TI  - Reliability and sensitivity to change of measurement instruments used in a
      traumatic brain injury population.
AB  - OBJECTIVE: To compile a minimum data set for the follow-up of traumatic brain
      injury patients from discharge from hospital to one year post injury to assess
      functioning and participation in the physical, cognitive and psychosocial
      domains, and in quality of life. DESIGN: Repeated questionnaire interviews by two
      observers to establish inter-observer reliability of the measurement instruments
      at discharge and at one year post injury, as well as their sensitivity to change
      over time in traumatic brain injury patients. SETTING: Department of neurosurgery
      of an academic hospital, department of a rehabilitation centre, and at the
      patients' homes in the Netherlands. SUBJECTS: The study at discharge included 25
      patients aged 18-50 years with a moderate to severe traumatic brain injury
      (Glasgow Coma Scale score 3-14), whereas the one year post injury study included
      14 patients aged 19-51 years. MAIN (OUTCOME) MEASURES: Physical domain: Barthel
      Index (BI), Functional Independence Measurement (FIM), Glasgow Outcome Scale
      (GOS), GOS Extended (GOSE). Cognitive domain: Disability Rating Scale (DRS),
      Functional Assessment Measurement (FAM), Levels of Cognitive Functioning Scale
      (LCFS), Neurobehavioural Rating Scale (NRS). Psychosocial domain: Community
      Integration Questionnaire (CIQ), Employability Rating Scale (ERS), Frenchay
      Activity Index (FAI), Multi Health Locus of Control (MHLC), Rehabilitation
      Activities Profile (RAP), Social Support List (SSL), Supervision Rating Scale
      (SRS), Wimbledon Self Reporting Rating Scale (WSRS). Quality of life: Coop/Wonca
      Charts (Coop), Rand SF-36 (Rand-36), Sickness Impact Profile-68 (SIP-68).
      RESULTS: At both discharge and at one year post injury, in the physical domain
      the FIM showed excellent squared weighted kappa (SWK ranging from 0.75 to 0.80),
      and intraclass correlation coefficient (ICC ranging from 0.75 to 0.92), and a
      relatively small standard error of measurement (SEM 3.22) and smallest detectable
      difference (SDD 8.92). In the cognitive domain the FAM and the NRS showed
      excellent SWK, and ICC, and a relatively small SEM and SDD. In the psychosocial
      domain the FAI showed excellent SWK (0.89), and ICC (0.87), and a relatively
      small SEM (2.64) and SDD (7.31). For quality of life, at both discharge and at
      one year post injury the SIP-68 and the Coop showed excellent SWK (0.87), and ICC
      (0.89), and a relatively small SEM (3.79) and SDD (10.51). At both time points
      SWK and ICC ranged from 0.80 to 0.89, SEM ranged from 1.47 to 1.98, and the SDD
      was 4.07. CONCLUSIONS: An example of a reliable minimum data set that is also
      able to detect changes over time is: the FIM, the FAM and the Coop for the early
      stages in recovery, extended with the NRS, the FAI, and the SIP-68 later in
      recovery, thereby covering all relevant domains after traumatic brain injury.

PMID- 16944827
TI  - Prediction of postoperative morbidity, mortality and rehabilitation in hip
      fracture patients: the cumulated ambulation score.
AB  - OBJECTIVE: To validate the cumulated ambulation score as an early postoperative
      predictor of short-term outcome in hip fracture patients. DESIGN: Prospective,
      descriptive study. SETTING: An orthopaedic hip fracture unit in a university
      hospital. PATIENTS: Four hundred and twenty-six consecutive hip fracture patients
      with an independent walking function admitted from their own home. Rehabilitation
      followed a well-defined multimodal rehabilitation regimen and discharge criteria.
      MAIN OUTCOME MEASURE: Admission tests with a new mobility score to assess
      prefracture functional mobility and a short mental score for cognitive
      dysfunction were performed. On the first three postoperative days patients were
      assessed with the cumulated ambulation score consisting of a cumulated assessment
      of simple ambulation characteristics with a score from 0 to 18 (fully mobile).
      The three assessments were correlated to short-term outcome parameters. RESULTS:
      The cumulated ambulation score was a highly significant predictor for length of
      hospitalization, time to discharge status, 30-day mortality and postoperative
      medical complications (P < 0.001 for all). The cumulated ambulation score was
      superior in its association with all postoperative outcome parameters to both the
      New Mobility Score and the mental score. A cumulated ambulation score of > or =
      10 correlated with a 99% survival at one month and 93% discharge to own home.
      CONCLUSION: The cumulated ambulation score is a potentially valuable score for
      early prediction of short-term postoperative outcome after hip fracture surgery.

PMID- 16944828
TI  - Relations between social support, appraisal and coping and both positive and
      negative outcomes for children of a parent with multiple sclerosis and
      comparisons with children of healthy parents.
AB  - OBJECTIVE: To examine adjustment in children of a parent with multiple sclerosis
      within a stress and coping framework and compare them with those who have
      'healthy' parents. SUBJECTS: A total of 193 participants between 10 and 25 years
      completed questionnaires; 48 youngsters who had a parent with multiple sclerosis
      and 145 youngsters who reported that they did not have a parent with an illness
      or disability. METHOD: A questionnaire survey methodology was used. Variable sets
      included caregiving context (e.g. additional parental illness, family
      responsibilities, parental functional impairment, choice in helping), social
      support (network size, satisfaction), stress appraisal, coping (problem solving,
      seeking support, acceptance, wishful thinking, denial), and positive (life
      satisfaction, positive affect, benefits) and negative (distress, health)
      adjustment outcomes. RESULTS: Caregiving context variables significantly
      correlated with poorer adjustment in children of a parent with multiple sclerosis
      included additional parental illness, higher family responsibilities, parental
      functional impairment and unpredictability of the parent's multiple sclerosis,
      and less choice in helping. As predicted, better adjustment in children of a
      parent with multiple sclerosis was related to higher levels of social support,
      lower stress appraisals, greater reliance on approach coping strategies (problem
      solving, seeking support and acceptance) and less reliance on avoidant coping
      (wishful thinking and denial). Compared with children of 'healthy' parents,
      children of a parent with multiple sclerosis reported greater family
      responsibilities, less reliance on problem solving and seeking social support
      coping, higher somatization and lower life satisfaction and positive affect.
      CONCLUSIONS: Findings delineate the key impacts of young caregiving and support a
      stress and coping model of adjustment in children of a parent with multiple
      sclerosis.

PMID- 16944829
TI  - Perceived pain and satisfaction with medical rehabilitation after hospital
      discharge.
AB  - OBJECTIVE: To examine the association between pain and satisfaction with medical
      rehabilitation in patients with hip or knee replacement approximately 90 days
      after discharge from inpatient medical rehabilitation. DESIGN: A cross-sectional
      design. PARTICIPANTS: The sample included 2507 patients with hip or knee
      replacement using information from the IT Health Track medical outcome database.
      MAIN OUTCOME MEASURE: Satisfaction with medical rehabilitation. RESULTS: The
      average age was 70.2 years, 66.5% were female, and 88.5% were non-Hispanic white.
      Pain scores were significantly and inversely associated with satisfaction with
      medical rehabilitation after adjustment for possible confounding factors. In
      patients with hip replacement each one-point increase in pain score was
      associated with a 10% decreased odds ratio (OR) of being satisfied with medical
      rehabilitation (OR 0.90, 95% confidence interval (CI) 0.84, 0.96). In patients
      with knee replacement, each one-point increase in pain score was associated with
      a 9% decreased odds ratio (OR 0.91, 95% CI 0.87, 0.96) of being satisfied with
      medical rehabilitation. CONCLUSION: Our data indicate that postoperative pain
      from hip or knee replacement is associated with reduced satisfaction with medical
      rehabilitation. Better postoperative pain control may improve a patient's level
      of satisfaction.

PMID- 16944830
TI  - [An introduction of the concept of social capital into health promotion
      activities].
AB  - Social factors, such as networks, institutions, trust, and social norms, are
      currently known as "Social Capital", the concept of which seeks to provide a
      basis for visualization and measurement of phenomena stemming from such factors.
      As a considerable amount of research has demonstrated that collective actions may
      be established with a greater degree of ease in communities with well-accumulated
      social factors, we can promote collective actions of Health Promotion activities
      through the concept of Social Capital and thereby establish more effective
      intervention. It is to be expected that theoretical research and operational
      experience using Social Capital may contribute to enhancing the effectiveness of
      Health Promotion activities, improving various health determinants through
      collective action.

PMID- 16944831
TI  - [A survey of subjective symptoms and life-style in junior high school students].
AB  - PURPOSE: A questionnaire survey was conducted to examine a relationship between
      indefinite complaints and life styles in junior high school students and to apply
      the results to life guidance. METHODS: Twenty nine public junior high schools
      were selected by random sampling of 13 cities and 3 towns in Kanagawa Prefecture.
      A self-reported questionnaire was supplied to all subjects, containing 100 life
      style related items, including a simplified CMI (Cornel Medical Index)
      questionnaire. RESULTS: The number of students who were evaluated as "point
      medical examination" based on physical symptoms of CMI and "disorder" based on
      the mental and physical symptom increased with the grade for both males and
      females. The students who reported "the life rhythm was always irregular" tended
      to be in the group evaluated as "disorder" or "point medical examination". The
      life rhythm was related to bedtime, sleeping hours and eating habits. It was
      observed that the students whose daily habits were always irregular had late
      bedtime, short sleeping hours and an irregular eating habit. As a result of the
      quantification method for the second type of analysis, it was found that sleeping
      time was the most related factor to the life rhythm. Furthermore 90% and more of
      students reported they did not consider nutritional balance with regard to their
      eating habits. CONCLUSION: It was suggested that those students who had irregular
      life rhythm needed sufficient sleep and nutrition guidance to maintain their
      health.

PMID- 16944832
TI  - [Mobile-phone e-mail use, social networks, and loneliness among Japanese high
      school students].
AB  - PURPOSE: The purposes of this study were to assess the loneliness of Japanese
      high school students who own and use a mobile phone, to clarify the relationships
      between students' loneliness and their social network and frequency of use of e
      mail feature, and to demonstrate relationships with a student's social network
      and recognition of the benefits and drawbacks of mobile phone use. METHOD: The
      participants were 227 students from two classes in each grade of a high school in
      the Kanto region of Japan. Participants answered a questionnaire covering the
      UCLA Loneliness Scale as well as questions pertaining to the circumstances of use
      of their mobile phones, their social networks (e.g., number of friends), and
      their perceptions of the benefits and drawbacks of mobile phone use. The
      questionnaires of students owning a mobile phone were analyzed. Total scores for
      the UCLA Loneliness Scale were calculated, and factor analysis was performed for
      the benefits and drawbacks. RESULT: A total of 220 questionnaires were returned,
      for which 94.1 percent of respondents owned a mobile phone. The percentages of
      male and female respondents were 58% and 42%. Chronbach's alpha for the UCLA
      Loneliness Scale (total score) was 0.87, a result similar to previous studies
      with high school and university students. Factor analysis revealed five factors
      associated with the benefits and drawbacks of mobile phone use. Multiple
      regression analysis showed that 42.9% of the variance in "frequency of e-mail
      use" was explained by grade level, frequency of mobile phone use, and two of the
      five factors from the benefits and drawbacks ("difficulty of communication," and
      "possible sleep loss due to nighttime e-mailing"). Stepwise multiple-regression
      analysis revealed that 24.4% of the variance in UCLA Loneliness Score was
      explained by gender, the frequency of e-mail use, the number of friends and the
      presence/absence of a girlfriend or boyfriend. CONCLUSION: Presence of an active
      social network and frequent e-mailing by mobile phone reduced students'
      loneliness. The frequency depended on their recognition of the benefits and
      drawbacks of mobile phone use and by the frequency of mobile phone use. This
      study established that students appreciate the usefulness of their mobile phone
      as an immediate communication tool, and are aware of its limitations. Although
      they experience frustration and lack of sleep (because of nighttime use),
      students use mobile phones to deepen their friendships.

PMID- 16944833
TI  - [The effects of various factors on cerebrovascular disease mortality rates in the
      20th century and future trends in Japan].
AB  - PURPOSES: To analyze the outcomes of measures designed to decrease
      cerebrovascular diseases (CVDs) in Japan and to project CVD mortality trends into
      the 21st century based on an analysis of rates observed in the 20th century.
      METHODS: The numbers of CVD deaths and population sizes from 1920 to 2003
      (excluding 1940 to 1946) by sex, year, and 5-year age group (from 20 to 79 years
      old) were used and effects of various factors on CVD mortality rates were
      estimated using Nakamura's Bayesian age-period-cohort model. The numbers of CVD
      deaths up to the year 2050 were projected based on estimates of age, cohort, and
      future period effects under three scenarios: (i) values remaining constant after
      year 2003; (ii) linearly extrapolated values; and (iii) quadratically
      extrapolated values, we obtained using a regression line for period effects from
      1995 to 2003. RESULTS: The age, cohort, and period effects on CVD mortality rates
      were large and in order of the magnitude of their ranges. There were small
      differences between males and females. The age effect increased with aging and
      the period effect started decreasing after 1970. The cohort effect was high for
      birth cohorts born from the 1840s to the 1890s and low for those born from the
      1920s to the 1970s. There were some differences in the cohort effect between
      males and females for birth cohorts born after 1940s; for females there was a
      gradual decrease, while for males there was a slight increase, after which it
      remained almost constant. According to the three scenarios, CVD deaths: (i) had
      upward trends through the projected period and peaked at around 2025 and 2045;
      (ii) remained almost constant at the present level for males, and decreased
      slightly for females; (iii) decreased for both males and females. CONCLUSIONS:
      The outcomes of measures designed to decrease CVDs were observed as period
      effects after 1970. Exposure to these measures is associated with prevention of
      CVD deaths. Nevertheless, in the first half of the 21st century, the number of
      CVD deaths is projected to increase due to the aging of the baby boomers and
      upward trends in the cohort effect for males. It would be necessary to adopt and
      develop both population strategies to decrease future period effects and high
      risk strategies to decrease cohort effects for younger males who are currently in
      their twenties and thirties.

PMID- 16944834
TI  - [Factors associated with social activities among the elderly in a metropolitan
      area: physical, psychological, and socio-environmental parameters].
AB  - OBJECTIVE: The current study examined physical, psychological, and socio
      environmental factors related to social activities among the elderly in a
      metropolitan area. METHODS: Fifteen hundred individuals aged 65 to 84 years were
      randomly selected in Osaka City. Data for 771 persons (51.4%) were obtained from
      a mail survey and these for 654 eligible cases were analyzed for level of social
      activities from four aspects: personal activities, socially-related activities,
      learning activities, and job activity. In order to examine factors related to
      social activities, we used logistic regression analyses with each of the four
      aspects of social activities as dependent variables. Independent variables were
      socio-demographic, physical, psychological, and socio-environmental variables.
      RESULTS: Multivariate analyses revealed the following results: no feeling of
      difficulty in going outdoors, number of friends, sense of collecting information
      about social activities, and informational social support were positively
      associated with personal activities. The attitude toward community score, the
      motivation to live comfortably score, the number of friends, opportunities to be
      invited to participate, any skill or knowledge, and experience in community
      activities were positively related to participation in socially-related
      activities. The attitude toward community score, opportunities to be invited to
      take part, and sense of collecting information about social activities were also
      positively associated with learning activities. Furthermore, motivation to active
      life score, any skill or knowledge, and experience in community activities were
      positively related to job activity. CONCLUSION: Physical, psychological, and
      socio-environmental factors as well as socio-demographic factors were found to be
      associated with social activities among the elderly in a metropolitan area.

PMID- 16944835
TI  - [The influence of grasping the need of residents on the implemention of municipal
      health services].

PMID- 16944836
TI  - Morphometric development of the posterior funicular nucleus in the human medulla
      oblongata.
AB  - Using serial sections of 11 human brains of fetuses 18-40 weeks of gestation
      (WG), 2-month-old infant and 63-year-old adult, we conducted the quantitative
      analysis of the development of the posterior funicular nucleus (PFN) in the
      medulla oblongata. The results suggest the following: (1) The cells of the human
      cuneatus lateralis nucleus are easily distinguished from those of the gracilis
      nucleus and cuneatus medialis nucleus because the neuronal somatic areas are the
      largest; the smallest neuronal areas are in the cuneatus medialis nucleus. (2)
      The development of the PFN occurs at least in four stages characterized by the
      degree of maturation of the neurons: (a) immature neuronal stage before 20 WG,
      (b) preparatory stage between (a) and (c), (c) accelerated development stage from
      30 to 40 WG, and (d) postnatal stage. The development of the human posterior
      funicular nucleus accelerates after 30 WG, and postnatal qualitative maturation
      also occurs. Developmental differences of the three nuclei of the PFN in the
      medulla oblongata are presented and discussed from the morphological and
      morphometric point of view.

PMID- 16944837
TI  - TMJ inflammation increases Fos expression in the nucleus raphe magnus induced by
      subsequent formalin injection of the masseter or hindpaw of rats.
AB  - The study was designed to examine the effect of persistent temporomandibular
      joint (TMJ) inflammation on neuronal activation in the descending pain modulatory
      system in response to noxious stimulus. Formalin was injected into the left
      masseter muscle or hindpaw of rats 10 days after injection of the left TMJ with
      saline or complete Freund's adjuvant (CFA). The results showed that 10-day
      persistent TMJ inflammation (induced by CFA) alone did not induce a significant
      increase in Fos-like immunoreactive (Fos-LI) neurons in the rostral ventromedial
      medulla (RVM) or locus coeruleus (LC), but that formalin injection of the
      masseter muscle or hindpaw induced a significant increase in Fos-LI neurons in
      the RVM and LC of rats with and without TMJ inflammation (P < 0.05). However,
      persistent TMJ inflammation significantly increased Fos-LI neurons in the nucleus
      raphe magnus (NRM) induced by subsequent formalin injection of the masseter
      muscle and hindpaw (70.2% increase and 53.8% increase, respectively, over the
      control TMJ-saline-injected rats; P < 0.05). The results suggest that persistent
      TMJ inflammation increases neuronal activity, in particularly in the NRM, by the
      plastic change of the descending pain modulatory system after ipsilateral
      application of a noxious stimulus to either orofacial area or a spatially remote
      body area.

PMID- 16944838
TI  - Comparative effects of milk and soymilk on bone loss in adult ovariectomized
      osteoporosis rat.
AB  - The present study was designed to investigate the comparative effects of milk and
      soymilk on the bone morphology of ovariectomized rat model with postmenopausal
      osteoporosis. Fourty 12-week-old female Spraque-Dawley rats were randomly divided
      into the following 5 groups: intact control (control), sham-operated (sham),
      ovariectomized (OVX), ovariectomized and fed milk (milk), ovariectomized and fed
      soymilk (soymilk) groups. Rats of OVX, milk and soymilk groups were bilaterally
      ovariectomized. Milk or soymilk of 3 ml was administered by gavage via an
      intragastric tube per day for 6 weeks. The distal femoral metaphysis was studied
      morphologically, together with bone mineral density (BMD), serum parathyroid
      hormone (PTH) and estradiol levels. In the OVX group, the trabecular bone volume
      was significantly reduced. The percentage area of resorbing surface was high. In
      the soymilk group, the trabecular bone volume was 68% higher and the percentage
      area of resorbing surface was 18% lower as compared with the OVX group. The serum
      estradiol level rose 48% and the serum PTH level fell 26% in the soymilk group.
      In the milk group, the trabecular bone volume had the tendency to be high, but
      there was no significant change of the bone morphology. The present study
      provides certain evidence that the soymilk has beneficial effects in preventing
      bone loss in rats induced by ovarian hormone deficiency.

PMID- 16944839
TI  - Effect of changes in food consistency on NADH-ubiquinone oxidoreductase activity
      and levels of mRNA for ND1, 51kDa, 75kDa and myosin heavy chain isoforms in two
      different portions of rat masseter muscle.
AB  - We investigated the effect of a change in food consistency on properties of the
      masseter muscle in 3-week-old rats fed a soft diet for 9 weeks (Group S) and fed
      a soft diet for 5 weeks followed by a hard diet for 4 weeks (Group S-H). The NADH
      O2 oxidoreductase activity, levels of mRNAs transcribed from genes encoding NADH
      ubiquinone oxidoreductase (Complex I: ND1, 51kDa, and 75kDa) and myosin heavy
      chain (MyHC) isoforms and the phenotype of the muscle fibers were measured in the
      superficial and deep portions of the muscle. In the period from 8 weeks to 12
      weeks of age, NADH-O2 oxidoreductase enzyme activity in both the superficial and
      deep portions of the muscle showed similar patterns in Group S and Group S-H. In
      contrast, the ND1, 51kDa and 75kDa mRNA levels in the superficial and deep
      portions of the masseter muscle in the Group S-H were higher than those of Group
      S in the 12-week-old rats, except for the 51kDa mRNA in the superficial portion
      of the masseter muscle. MyHC-IIa and MyHC-IId/x mRNA levels in the superficial
      portion of the masseter muscle were higher in the Group S-H than in the Group S.
      These observations suggest that short-term feeding stress such as the transition
      from a soft diet to a hard diet causes changes in oxidative metabolism, in mRNA
      levels for the Complex I components ND1 and 75kDa, and the mRNA levels for the
      MyHC isoforms IIa and IId/x in the superficial portion of rat masseter muscle,
      but no changes in the composition of muscle fiber types.

PMID- 16944840
TI  - [Recent progress in structural biology of AGC protein kinases].

PMID- 16944841
TI  - [Role of phosphatidylinositol 3-kinase in the immune system].

PMID- 16944842
TI  - [Chimera photoreceptor, neochrome, has arisen twice during plant evolution].

PMID- 16944843
TI  - [Function of microtubules at the onset of cytokinesis].

PMID- 16944844
TI  - [Selective packaging mechanism for influenza A virus].

PMID- 16944845
TI  - [Novel intracellular signal transduction of dopamine D2 receptor in
      schizophrenia].

PMID- 16944846
TI  - [Definitions of key words in stem cell biology].

PMID- 16944847
TI  - [From glutathione metabolism to sugar-chain biology].

PMID- 16944848
TI  - Evaluating evidence-based practice performance.

PMID- 16944849
TI  - Fondaparinux reduced death or reinfarction in acute ST-segment elevation
      myocardial infarction.

PMID- 16944850
TI  - Enoxaparin for 7 days was better than unfractionated heparin for 2 days for
      reducing death and MI but not bleeding in STEMI.

PMID- 16944851
TI  - Fondaparinux was noninferior to enoxaparin for death, MI, and refractory ischemia
      but reduced bleeding in angina and non-STEMI.

PMID- 16944852
TI  - Review: ACE inhibitors reduce mortality and cardiovascular endpoints in stable
      coronary artery disease.

PMID- 16944853
TI  - Clopidogrel plus aspirin did not differ from aspirin alone for reducing MI,
      stroke, and CV death in high-risk atherothrombosis.

PMID- 16944854
TI  - Intensive insulin therapy reduced morbidity but not mortality in patients in the
      medical intensive care unit.

PMID- 16944855
TI  - Review: ACE inhibitors delay onset of microalbuminuria in diabetes without
      nephropathy and reduce mortality in diabetic nephropathy.

PMID- 16944856
TI  - Review: the renoprotective effects of ACE inhibitors and ARBs independent of
      blood pressure control are uncertain.

PMID- 16944857
TI  - Review: surgical site, advanced age, and comorbid conditions increase risk for
      postoperative pulmonary complications.

PMID- 16944858
TI  - Review: lung expansion modalities and selective nasogastric decompression prevent
      postoperative pulmonary complications.

PMID- 16944859
TI  - Formoterol in addition to tiotropium improved airflow obstruction in chronic
      obstructive pulmonary disease.

PMID- 16944860
TI  - Dietetic assistants improved postoperative clinical outcomes in older women with
      hip fracture.

PMID- 16944861
TI  - Laparoscopic gastric band surgery was more effective than an intensive
      nonsurgical intervention for weight loss in mild-to-moderate obesity.

PMID- 16944862
TI  - Lifestyle recommendations plus the DASH diet reduced hypertension in patients
      with above-optimal blood pressure.

PMID- 16944863
TI  - Review: oral appliances are better than control appliances, but not CPAP, in the
      obstructive sleep apnea-hypopnea syndrome.

PMID- 16944864
TI  - Review: sparse evidence supports lifestyle modifications for reducing symptoms of
      gastroesophageal reflux disease.

PMID- 16944865
TI  - Review: antiviral agents reduce risk for influenza in healthy adults and
      alleviate symptoms faster than placebo.

PMID- 16944866
TI  - Review: probiotics are effective for prevention of antibiotic-associated diarrhea
      and treatment of Clostridium difficile disease.

PMID- 16944867
TI  - Review: ribavirin is not better than placebo in chronic hepatitis C infection.

PMID- 16944868
TI  - Review: topical quinolones are better than systemic antibiotics for chronic
      suppurative otitis media at up to 2 weeks.

PMID- 16944870
TI  - Galantamine was effective in mild-to-moderate Alzheimer disease.

PMID- 16944869
TI  - Bovine lactoferrin added to triple therapy increased Helicobacter pylori
      eradication rate.

PMID- 16944871
TI  - Review: magnetic resonance imaging alone is of limited usefulness in diagnosing
      multiple sclerosis.

PMID- 16944872
TI  - The Thrombolysis in Myocardial Infarction risk index predicted in-hospital
      mortality in non-ST-segment elevation myocardial infarction.

PMID- 16944873
TI  - A clinical prediction model was sensitive but not specific for predicting
      mortality in pulmonary embolism.

PMID- 16944875
TI  - Parallel chemical dosing of subcellular targets.
AB  - To characterize the role of spatially heterogeneous signaling in cellular
      function, methods are required for differentially exposing distinct regions of
      individual cells to externally applied reagents. Although a range of standard
      approaches exists for generating localized chemical gradients in culture,
      including puffer pipet spritzing and photolytic release of caged effectors, each
      is limited in key respects. Here, we report development of a cell-dosing strategy
      that addresses these limitations, providing the means to create steep gradients
      of any aqueous-miscible compound at essentially unlimited numbers of sites in
      parallel. In this approach, cells are cultured on a micrometer-thick polymer
      membrane that serves as a barrier between two stacked laminar-flow channels: one
      containing the cell culture and the other serving as a reagent flow cell. By
      focusing a pulsed laser beam onto one or more selected membrane positions,
      micrometer-diameter pores can be ablated upstream of desired cellular targets.
      Nascent pores thus serve as ports of entry into the culture environment for
      reagent streams capable of modifying subcellular features at positions
      potentially hundreds of micrometers from ablation sites. Importantly, individual
      reagent streams also can be rapidly eliminated by photo-cross-linking a protein
      plug over a selected pore. This versatile strategy for dynamically reshaping the
      chemical microenvironments in which cells reside should be useful in a variety of
      cell biology applications, ranging from neurotrophic modulation of neurite
      pathfinding to stimulation of cellular networks.

PMID- 16944874
TI  - Reproducible two-dimensional capillary electrophoresis analysis of Barrett's
      esophagus tissues.
AB  - We have constructed a high-speed, two-dimensional capillary electrophoresis
      system with a compact and high-sensitivity fluorescence detector. This instrument
      is used for the rapid and reproducible separations of Barrett's esophagus tissue
      homogenates. Proteins and biogenic amines are labeled with the fluorogenic
      reagent 3-(2-furoyl)quinoline-2-carboxaldehyde. Labeled biomolecules are
      separated sequentially in two capillaries. The first capillary employs capillary
      sieving electrophoresis using a replaceable sieving matrix. Fractions are
      successively transferred to a second capillary where they undergo additional
      separation by micellar electrokinetic capillary chromatography. The comprehensive
      two-dimensional separation requires 60 min. Within-day migration time
      reproducibility is better than 1% in both dimensions for the 50 most intense
      features. Between-day migration time precision is 1.3% for CSE and better than
      0.6% for MECC. Biopsies were obtained from the squamous epithelium in the
      proximal tubular esophagus, Barrett's epithelium from the distal esophagus, and
      fundus region of the stomach from each of three Barrett's esophagus patients with
      informed consent. We identified 18 features from the homogenate profiles as
      biogenic amines and amino acids. For each of the patients, Barrett's biopsies had
      more than 5 times the levels of phenylalanine and alanine as compared to squamous
      tissues. The patient with high-grade dysplasia shows the highest concentrations
      for 13 of the amino acids across all tissue types. Concentrations of glycine are
      40 times higher in squamous biopsies compared to Barrett's and fundal biopsies
      from the patient with high-grade dysplasia. These results suggest that two
      dimensional capillary electrophoresis may be of value for the rapid
      characterization of endoscopic and surgical biopsies.

PMID- 16944876
TI  - Handheld rectilinear ion trap mass spectrometer.
AB  - A shoebox-sized, 10-kg, handheld mass spectrometer, Mini 10, based on a
      rectilinear ion trap mass analyzer has been designed, built, and characterized.
      This instrument has evolved from a decade-long experimental and simulation
      program in mass spectrometer miniaturization. The rectilinear ion trap has a
      simplified geometry and high trapping capacity, and when used with a miniature
      and ruggedized pumping system, it allows chemical analysis while the instrument
      is being carried. Compact electronics, including an air core RF drive coil, were
      developed to control the instrument and to record mass spectra. The instrument
      runs on battery power, consuming less than 70 W, similar to a laptop computer.
      Wired and wireless networking capabilities are implemented. The instrument gives
      unit resolution and a mass range of over m/z 500. Tandem mass spectrometry
      capabilities are implemented using collision-induced dissociation, and they are
      used to provide confirmation of chemical structure during in situ analysis.
      Continuous monitoring of air and solution samples is demonstrated, and a limit of
      detection of 50 ppb was obtained for toluene vapor in air and for an aqueous
      naphthalene solution using membrane sample introduction.

PMID- 16944877
TI  - Characterization of chloramphenicol palmitate drug polymorphs by Raman mapping
      with multivariate image segmentation using a spatial directed agglomeration
      clustering method.
AB  - Chemical imaging analysis holds great potential in probing the chemical
      heterogeneity of samples with high spatial resolution and molecular specificity.
      This paper demonstrates the implementation of Raman mapping for microscopic
      characterization of tablets containing chloramphenicol palmitate polymorphs with
      the aid of a new multivariate image segmentation approach based on spatial
      directed agglomeration clustering. This approach performs the agglomeration
      clustering by stepwise merging the pixels possessing both spatial closeness and
      spectral similarity into clusters that define the image segmentation. The
      incorporation of spatial closeness into the clustering process enables the
      approach to improve the robustness and avoid poorly defined image segmentation
      arising from clusters with highly separated pixels. Additionally, the stepwise
      merging of clusters offers an F-statistic-based procedure to automatically
      ascertain the number of image segments. Raman mapping analysis of tablets
      containing two polymorphs of chloramphenicol palmitate followed by multivariate
      image segmentation reveals that the proposed technique offers the identification
      of each polymorph and a quantitative visualization of the spatial distribution of
      the polymorphs identified. This technique holds promise in rapid, noninvasive,
      and quantitative polymorph analysis for pharmaceutical production processes.

PMID- 16944878
TI  - Determination of low molecular weight dicarboxylic and ketocarboxylic acids in
      seawater samples.
AB  - We report a new method developed for the isolation and determination of low
      molecular weight dicarboxylic acids and related polar compounds (C2-C9) from
      seawater samples. The seawater sample was first acidified and then passed through
      an activated charcoal column to adsorb the dicarboxylic acids. They are then
      desorbed with NH4OH/methanol/water mixture and derivatized with BF3/1-butanol to
      dibutyl esters, which are determined using a capillary GC/FID. We tested
      different pH (0.5, 1, 1.5) and different amounts of charcoal (100, 200, 300, 500
      mg) to maximize the recovery of dicarboxylic acids. Using 300 mg of activated
      charcoal for 100 mL of sodium chloride solution acidified at pH 1, the recoveries
      for C2, C3, C4, C5, C6, C7, C8, and C9 were 61, 49, 96, 84, 77, 67, 57, and 53%,
      respectively. We applied this method to real seawater samples collected from the
      northwestern Mediterranean Sea. Here, we report, for the first time,
      concentrations of a homologous series of C2-C9 dicarboxylic acids as well as
      ketocarboxylic acids including glyoxylic and 4-oxobutanoic acids in surface water
      and deep seawater samples, with glyoxylic acid being the dominant species (8-40
      microg L(-1)). This method allows the detection of dicarbonyls such as glyoxal in
      the samples although its quantification is not possible.

PMID- 16944879
TI  - Scanning electrochemical microscopy investigations of monolayers bound to p-type
      silicon substrates.
AB  - p-Si type electrodes modified with different organic monolayers were investigated
      by reaction with radical anion and cation electrogenerated at a microelectrode
      operating in the configuration of a scanning electrochemical microscope. The
      method proves to be a convenient tool for investigating both the quality and the
      redox properties of the layer as previously demonstrated on metallic electrodes
      especially when the sample cannot be electrically connected. Approach curves
      recorded with the different mediators were used to investigate the electron
      transfer rates across alkyl monolayers bound to p-type silicon substrates.
      Preliminary results indicate that the interfacial electron transfer occurs via
      electron tunneling through the organic layer as generally described for SAMs
      grafted on gold electrodes.

PMID- 16944880
TI  - Microdialysis sampling membrane performance during in vitro macromolecule
      collection.
AB  - Microdialysis sampling is well-established for sampling small molecules.
      Recently, there has been an increased interest toward collecting macromolecules
      using microdialysis sampling. In this work, fluorescein isothiocyanate-labeled
      dextrans (FITC-dextrans) with molecular weight between 10 and 70 kDa were chosen
      as representative molecules to study analyte mass transport properties during
      microdialysis sampling using different lengths (2 and 10 mm) of 100-kDa MWCO
      polyethersulfone membranes. Experiments were performed in both well-stirred and
      quiescent phosphate-buffered saline solutions as well as in a 0.3% agar solution.
      Different fundamental parameters affecting microdialysis sampling of
      macromolecules, including effective membrane diffusion coefficients, were
      evaluated. The applicability of the most-often-cited Bungay et al. mass transfer
      model was compared to experimental data for the FITC-dextrans. For the larger
      macromolecules, the membrane provides a significant mass transport resistance
      most likely caused by hindered diffusion. These experimental aspects that are
      critical to microdialysis sampling of macromolecules are presented.

PMID- 16944881
TI  - Unlimited-volume electrokinetic stacking injection in sweeping capillary
      electrophoresis using a cationic surfactant.
AB  - Sweeping is an effective and convenient way for online sample preconcentration in
      micellar electrokinetic chromatography. The usual procedure includes a
      hydrodynamic injection step carried out by applying pressure to the sample vial
      followed by the subsequent sweeping and separation processes. The injected sample
      volume is limited by the dimensions of the capillary because a part of the
      capillary has to be left free of sample solution for the subsequent sweeping and
      separation steps. In addition, when a short capillary, such as 4-10 cm, is used
      for sweeping, the injected sample volume is small even if the entire capillary is
      filled with sample solution. To solve this problem, an electrokinetic stacking
      injection (EKSI) scheme was developed by using a cationic surfactant,
      dodecyltrimethylammonium bromide, for sweeping in capillary electrophoresis. An
      experimental model was proposed, and the entire process was theoretically
      analyzed. According to the theoretical discussion, the optimal conditions for two
      model analytes, 5-carboxyfluorescein (5-FAM) and sodium fluorescein (FL), were
      experimentally determined. The injected sample plug lengths for 5-FAM and FL
      under 20.1 kV for 60 min were experimentally estimated as 836 and 729 cm,
      corresponding to 28- and 24-fold the effective capillary length, respectively.
      The EKSI scheme resulted in increased detection factors for 5-FAM and FL of 4.5 x
      10(3) and 4.0 x 10(3) using 60-min injection relative to a traditional pressure
      injection.

PMID- 16944882
TI  - Centrifuge microextraction coupled with on-line back-extraction field-amplified
      sample injection method for the determination of trace ephedrine derivatives in
      the urine and serum.
AB  - Although sample stacking has enjoyed some degree of success in electrophoretic
      separation techniques, there is still a major problem with complex matrix sample
      as it suffers tremendously from sample matrix effects. A novel method that
      combines two concentration techniques, centrifuge microextraction (CME) and on
      line back-extraction field-amplified sample injection (OLBE-FASI), is used to
      determine trace ephedrine derivatives in urine and serum by capillary zone
      electrophoresis. The CME, integrating the sample cleanup and preconcentration
      into a single step, is a promising sample preparation method for biological
      samples. The CME technique provided 9-14-fold enrichment within 10 min. The OLBE
      FASI eliminated the need to perform solvent exchange and provided a further
      concentration of the analytes. Using CME coupled with OLBE-FASI, over a 3800-fold
      increase in sensitivity could be obtained as compared with the normal
      hydrodynamic injection without sample stacking. For a 1-mL urine sample, the
      linear range was 5/10-200 ng/mL with the square of the correlation coefficients
      (r(2)) ranging from 0.9988 to 0.9994. Detection limits were from 0.15 to 0.25
      ng/mL using a photodiode array UV detection at wavelength 192 nm. The possibility
      of this method to determine ephedrine derivatives in 20-muL serum samples was
      also demonstrated.

PMID- 16944883
TI  - Ferrocene peapod modified electrodes: preparation, characterization, and
      mediation of H2O2.
AB  - Electrochemical properties of a new nanomaterial ferrocene (Fc) peapod, Fc-filled
      single-walled carbon nanotubes (Fc@SWNTs), have been investigated in an aqueous
      solution in detail by preparing different kinds of Fc@SWNTs-modified glassy
      carbon electrodes (Fc@SWNTs/GCE and Fc@SWNTs-gel/GCE). One pair of surface
      confined redox waves corresponding to the couple of Fc/Fc+ is obtained, which
      indicates that Fc encapsulated inside SWNTs retains electrochemical activity. The
      Fc@SWNTs-gel/GCE shows better electrochemical reversibility due to the existence
      of room temperature ionic liquid (RTIL). Furthermore, it shows excellent
      mediation of H2O2 based on Fc/Fc+ used as electron-transfer mediators for
      oxidation of H2O2 to O2 and reduction to H2O, suggesting specific properties of
      Fc@SWNTs due to a combination of Fc and SWNTs. The interaction between Fc and
      SWNTs is also characterized by UV-vis-NIR spectrometry and Raman spectrometry. A
      Fc@SWNTs-based sensor for H2O2 with a determination limit of 5 microM is
      fabricated, and it shows good stability and reproducibility. This work not only
      demonstrates that the Fc peapod is a new kind of functional nanomaterial but also
      appears promising in constructing novel chemical and biosensors and fuel cells.

PMID- 16944884
TI  - Surfactant-induced modulation of light emission in porous silicon produced by
      metal-assisted electroless etching.
AB  - Photoluminescent porous silicon (PSi) was produced by Pt-assisted electroless
      chemical etching of p(-)-Si in a 1:1:2 (v/v/v) solution of HF, methanol, and
      H2O2. Upon irradiation with ultraviolet light PSi produced under these conditions
      luminesces with a peak emission near 590 nm that is sufficiently intense to be
      visible by eye. Because PSi light emission is an attractive modality for chemical
      sensing, the effect of charged surfactant adsorbates on the photoluminescence
      (PL) intensity was investigated. PSi was exposed to aqueous solutions of
      cationic, cetyltrimethylammonium bromide (CTAB), and anionic, sodium dodecyl
      sulfate (SDS), surfactants as a function of solution concentration and pH.
      Adsorption produces both chemical and physical changes at the PSi-solution
      interface, which were followed by a combination of PL and infrared absorption
      spectroscopy. Luminescence is quenched in the presence of CTAB and enhanced in
      the presence of SDS, both in a pH-dependent manner, the behavior being explained
      by a depletion layer model. PSi crystallites generated from p-Si exhibit a hole
      depletion layer at the Si-solution interface, and the depletion layer expands in
      the presence of cationic surfactant and contracts in the presence of anionic
      surfactant. Because the surface depletion region is nonemissive (dead layer),
      surfactant adsorbate-induced modulation of the depletion layer width determines
      the luminescence intensity of PSi. At very basic pH, PL quenching was observed
      independent of surfactant identity or concentration, an observation likely tied
      to the dissolution of the PSi nanocrystallites in strong base.

PMID- 16944885
TI  - Metal affinity capture tandem mass spectrometry for the selective detection of
      phosphopeptides.
AB  - We report a new method called metal affinity capture that when coupled with
      tandem mass spectrometry (MAC-MSMS) allows for the selective detection and
      identification of phosphopeptides in complex mixtures. Phosphopeptides are
      captured as ternary complexes with Ga(III) or Fe(III) and N(alpha),N(alpha)
      bis(carboxymethyl)lysine (LysNTA) in solution and electrosprayed as doubly or
      triply charged positive ions. The gas-phase complexes uniformly dissociate to
      produce a common (LysNTA + H)+ ion that is used as a specific marker in precursor
      ion scans. The advantages of MAC-MSMS over the current methods of phosphopeptide
      detection are as follows. (1) MAC-MSMS uses metal complexes that self-assemble in
      solution at pH <5, which is favorable for the production of positive ions by
      electrospray. (2) Phosphorylation at tyrosine, serine, and threonine is detected
      by MAC-MSMS. (3) The phosphopeptide peaks in the mass spectra are encoded with
      the 69Ga-71Ga isotope pattern for selective recognition in mixtures. Detection by
      MAC-MSMS of singly and multiply phosphorylated peptides in tryptic digests is
      demonstrated at low-nanomolar protein concentrations.

PMID- 16944886
TI  - Double-cross hydrostatic pressure sample injection for chip CE: variable sample
      plug volume and minimum number of electrodes.
AB  - A novel sample injection method for chip CE was presented. This injection method
      uses hydrostatic pressure, generated by emptying the sample waste reservoir, for
      sample loading and electrokinetic force for dispensing. The injection was
      performed on a double-cross microchip. One cross, created by the sample and
      separation channels, is used for formation of a sample plug. Another cross,
      formed by the sample and controlling channels, is used for plug control. By
      varying the electric field in the controlling channel, the sample plug volume can
      be linearly adjusted. Hydrostatic pressure takes advantage of its ease of
      generation on a microfluidic chip, without any electrode or external pressure
      pump, thus allowing a sample injection with a minimum number of electrodes. The
      potential of this injection method was demonstrated by a four-separation-channel
      chip CE system. In this system, parallel sample separation can be achieved with
      only two electrodes, which is otherwise impossible with conventional injection
      methods. Hydrostatic pressure maintains the sample composition during the sample
      loading, allowing the injection to be free of injection bias.

PMID- 16944887
TI  - Mass spectrometry-based glycomics strategy for exploring N-linked glycosylation
      in eukaryotes and bacteria.
AB  - N-Glycosylation of proteins is recognized as one of the most common
      posttranslational modifications in eukaryotes. To date, most glycomics techniques
      are limited to examining eukaryotic pathways. Technologies capable of
      characterizing newly described N-linked glycosylation systems in bacteria from
      biologically relevant samples in an accurate, rapid, and cost-effective manner
      are needed. In this paper, a new glycomics strategy, based on the combination of
      nonspecific proteolytic digestion and permethylation, was devised that can be
      used for both eukaryotic and bacterial glycoproteins. Eukaryotic glycoproteins
      were digested with Pronase E with a higher ratio (enzyme/protein, 2:1-3:1) and a
      longer reaction time (48-72 h). The Asn-glycans were then purified using porous
      graphitic carbon cartridges followed by permethylation. The mass spectrometric
      data indicated that hydroxyl groups were methylated, while the amino group in
      asparagine underwent beta-elimination. Both modifications were evident from an
      increase of 111 Da in the molecular masses of permethylated Asn-glycans compared
      to the corresponding free oligosaccharides. NMR spectroscopy corroborated these
      results by showing that the mass difference resulted from beta-elimination of the
      free amino group in the asparagine residue. The method was validated with the
      characterization of the N-linked glycoproteins in total protein extracts from the
      bacterium Campylobacter jejuni 11168H. In addition to detecting the Asn-linked
      bacterial heptasaccharide, we also observed an unexpected free heptasaccharide
      intermediate that required a functional glycosylation pathway. These results
      demonstrate the usefulness of this method for screening N-linked glycans
      expressed by eukaryotes and bacteria and for detecting novel intermediates of N
      linked glycosylation pathways.

PMID- 16944888
TI  - Nanoparticle-based continuous full filling capillary
      electrochromatography/electrospray ionization-mass spectrometry for separation of
      neutral compounds.
AB  - Highly efficient reversed-phase capillary electrochromatography (CEC) separations
      (plate numbers up to 700 000/m), with electrospray ionization mass spectrometry
      detection were achieved utilizing novel dextran-coated polymer nanoparticles as a
      pseudostationary phase. A continuous full filling (CFF) technique in which
      nanoparticles are continuously introduced into the capillary was employed for
      separation of neutral analytes (dialkyl phthalates), utilizing an orthogonal
      electrospray interface to prevent nanoparticles from entering the mass
      spectrometer. CFF-CEC benefits from that an entirely fresh column is employed for
      every analysis, avoiding carryover effects associated with stationary-phase
      contamination. The highly efficient separations obtained were accomplished by
      optimizing the organic modifier concentration in the electrolyte and by using a
      high nanoparticle concentration (5 mg/mL), to improve interparticle mass transfer
      and gain sufficient retention. Nanoparticles, with an average diameter of 600 nm,
      were prepared by polymerization of methacrylic acid and trimethylolpropane
      trimethacrylate, which in turn were coated with dextran. These nanoparticles
      formed stable suspensions in electrolytes having broad ranges of polarities,
      enabling straightforward optimization of the reversed-phase conditions.

PMID- 16944889
TI  - Electrochemical detection of single-nucleotide mismatches using an electrode
      microarray.
AB  - Gold electrode arrays with electrode diameters of 10 mum were used for the
      detection of eight single-nucleotide mismatches in unlabeled and prehybridized
      DNA by electrochemical impedance spectroscopy (EIS). Because of the differences
      in the electrical properties of films of duplex DNA (normal duplex DNA in B-form)
      in the presence and absence of Zn(2+) at pH > or = 8.6, Randles equivalent
      circuits were employed to evaluate the EIS results. The difference in the charge
      transfer resistance (DeltaR(CT)) between B-DNA (absence of Zn2+ at pH > or = 8.6)
      and M-DNA (presence of Zn2+ at pH > or = 8.6) allows unequivocal detection of all
      eight single-nucleotide mismatches within a 20-mer DNA sequence. After
      dehybridization/rehybridization with target DNA, DeltaR(CT) allows the
      discrimination of single-nucleotide mismatches with concentrations of the target
      strand as low as 10 fM. Although the presence of protein impurities (bovine serum
      albumin, 10 microg/mL) interferes with the detection of the target strand (1 pM
      detection limit), the presence of nontarget DNA (calf thymus DNA, 10(-8) M) does
      not interfere, and the detection limit for recognition of the target strand
      remains at 10 fM.

PMID- 16944890
TI  - Electroanalysis using macro-, micro-, and nanochemical architectures on electrode
      surfaces. Bulk surface modification of glassy carbon microspheres with gold
      nanoparticles and their electrical wiring using carbon nanotubes.
AB  - Gold nanoparticles (approximately 30-60 nm in diameter) were deposited onto the
      surface of glassy carbon microspheres (10-20 microm) through electroless plating
      to produce bulk (i.e., gram) quantities of nanoparticle surface-modified
      microspheres. The gold nanoparticle-modified powder was then characterized by
      means of scanning electron microscopy and cyclic voltammetry. The voltammetric
      response of a macroelectrode consisting of a film of gold nanoparticle-modified
      glassy carbon microspheres, bound together and "wired-up" using multiwalled
      carbon nanotubes (MWCNTs), was investigated. We demonstrate that by intelligently
      exploiting both nano- and microchemical architectures and wiring up the
      electroactive centers using MWCNTs in this way, we can obtain macroelectrode
      voltammetric behavior while only using approximately 1% by mass of the expensive
      gold material that would be required to construct the equivalent gold film
      macrodisk electrode. The potential utility of electrodes constructed using
      chemical architectures such as this was demonstrated by applying them to the
      analytical determination of arsenic(III) concentration. An optimized limit of
      detection of 2.5 ppb was obtained.

PMID- 16944891
TI  - Automated determination of silicon isotope natural abundance by the acid
      decomposition of cesium hexafluosilicate.
AB  - A procedure for the automated determination of isotopic abundances of silicon
      from biogenic and lithogenic particulate matter and from dissolved silicon in
      fresh or saltwaters is reported. Samples are purified using proven procedures
      through the reaction of Si with acidified ammonium molybdate, followed by
      precipitation with triethylamine and combustion of the precipitate to yield
      silicon dioxide. The silicon dioxide is converted to cesium hexafluosilicate by
      dissolution in hydrogen fluoride and the addition of cesium chloride. Isotopic
      analysis is accomplished by decomposing the cesium hexafluosilicate with
      concentrated sulfuric acid to generate silicon tetrafluoride gas. Silicon
      tetrafluoride is purified cryogenically and analyzed on a gas source isotope
      ratio mass spectrometer. Yields of silicon tetrafluoride are >99.5%. The
      procedure can be automated by modifying commercial inlet systems designed for
      carbonate analysis. The procedure is free of memory effects and isotopic biases.
      Reproducibility is +/-0.03-0.10 per thousand for a variety of natural and
      synthetic materials.

PMID- 16944892
TI  - Probing mercury species-DNA interactions by capillary electrophoresis with on
      line electrothermal atomic absorption spectrometric detection.
AB  - The interactions of inorganic mercury Hg(II), methylmercury (MeHg(I)),
      ethylmercury (EtHg(I)), and phenylmercury (PhHg(I)) with DNA have been probed by
      capillary electrophoresis with on-line electrothermal atomic absorption
      spectrometric detection (CE-ETAAS) in combination with circular dichroism and
      Fourier transform infrared spectroscopy. The CE-ETAAS assay allows sensitive
      probing of the level of DNA damage by mercury species, extraction of
      thermodynamic and kinetic information on the interactions of mercury species with
      DNA, and provides direct evidence for the formation of mercury species-DNA
      adducts. The binding affinity of mercury species to DNA increases in order of
      Hg(II) < EtHg(I) approximately PhHg(I) approximately MeHg(I). The interactions of
      mercury species with DNA follow a first-order kinetics for mercury species and
      zero-order kinetics for DNA. Mercury highly covalently coordinates to endocyclic
      and exocyclic N sites of DNA bases. However, the interactions of DNA with
      mercuric species cause no transition of the DNA original conformation. The
      results reveal that organomercuric species exhibit stronger affinity and faster
      binding to DNA and show more potential damage to DNA than Hg(II) in view of the
      kinetic and thermodynamic evaluations. Moreover, MeHg(I) exhibits the fastest
      binding to DNA, suggesting that MeHg(I) enjoys superiority over the other
      mercuric species for rapid formation of a stable complex with DNA, whereas Hg(II)
      shows the slowest binding to DNA. The present study provides new evidence and
      understanding of the binding modality of mercuric species to DNA.

PMID- 16944893
TI  - Analysis of structurally heterogeneous Langmuir-Blodgett films of folded/unfolded
      long-chain molecules by infrared multiple-angle incidence resolution
      spectroscopy.
AB  - Infrared multiple-angle incidence resolution spectroscopy (IR MAIRS) has been
      employed for the structural analysis of a heterogeneous multilayer Langmuir
      Blodgett (LB) film of ketomycolic acid (keto-MA). Keto-MA was chosen for the
      study because the molecule changes its conformation largely, which depends on the
      layer structure of the LB film: the long alkyl chain with a keto group remains
      folded when it has no counter layer for interdigitation. IR MAIRS is a surface
      analytical technique that was originally developed to analyze anisotropic
      structure in a thin film prepared on an IR transparent material. In the present
      study, however, a newly found characteristic of MAIRS has been used to discuss
      the molecular conformation and the interdigitation architecture between two
      adjacent monolayers. As expected theoretically, the molecular folding was clearly
      detected as "IR MAIRS shift". Subtraction of the IR MAIRS spectra of single- and
      triple-monolayer LB film of keto-MA yielded unambiguous results for the
      interdigitated double layer in the triple-monolayer LB film, and the layer
      sequence was also revealed.

PMID- 16944894
TI  - Delta34S measurements of sulfur by multicollector inductively coupled plasma mass
      spectrometry.
AB  - An accurate and precise method for the determination of delta34S measurements by
      multicollector inductively coupled plasma mass spectrometry has been developed.
      Full uncertainty budgets, taking into consideration all the uncertainties of the
      measurement process, have been calculated. The technique was evaluated by
      comparing measured values with a range of isotopically enriched sulfur solutions
      prepared by gravimetric addition of a 34S spike. The gravimetric and measured
      results exhibited a correlation of R2 >0.999. Repeat measurements were also made
      after adding Na (up to 420 microg g(-1)) and Ca (up to 400 microg g(-1)) salts to
      the sulfur standard. No significant deviations in the delta34S values were
      observed. The Russell correction expression (Ingle, C.; Sharp, B.; Horstwood, M.;
      Parrish, R.; Lewis, D. J. J. Anal. At. Spectrom. 2003, 18, 219) was used to
      correct for mass bias on the 34S/32S isotope amount ratio from the mass bias
      observed for the 30Si/28Si isotope amount ratio. Consistent compensation for
      instrumental mass bias was achieved. Resolution of the measured delta34S values
      was better than 1 per thousand after consideration of all uncertainty components.
      The technique was evaluated for practical applications by measurement of delta34S
      for a range of mineral waters by pneumatic nebulization sample introduction and
      the analysis of genuine and counterfeit pharmaceuticals using both laser ablation
      sample introduction and liquid chromatography. For the former two cases
      polyatomic interferences were resolved by operating the MC-ICPMS in medium
      resolution, while for the chromatographic analyses polyatomic interferences were
      minimized by the use of a membrane desolvator, allowing the instrument to be
      operated at a resolution of 400.

PMID- 16944895
TI  - Characterization of laser-induced acoustic desorption coupled with a Fourier
      transform ion cyclotron resonance mass spectrometer.
AB  - Several experimental factors have been investigated that influence the efficiency
      of desorption and subsequent chemical ionization of nonvolatile, thermally labile
      molecules during laser-induced acoustic desorption/Fourier transform ion
      cyclotron resonance mass spectrometry (LIAD/FT-ICR) experiments. The experiments
      were performed by using two specially designed LIAD probes of different outer
      diameters (1/2 and 7/8 in.) and designs. Several improvements to the design of
      the "first generation" (1/2 in.) LIAD probe are presented. The larger diameter
      (7/8 in.) probe provides a larger surface area for desorption than the smaller
      diameter probe. Further, it was designed to desorb molecules on-axis with the
      magnetic field of the instrument. This is in contrast to the smaller probe for
      which desorption occurs 1.3 mm off-axis. This improved alignment, which provides
      better overlap between the desorbed molecules and trapped reagent ions, results
      in a substantial increase in the sensitivity of LIAD analyses. The thickness of
      the sample layer deposited on the irradiated metal foil and the number of laser
      shots fired on the backside of the foil were found to have a significant effect
      on the overall signal and the relative abundances of the ions formed in the
      experiment. Evaporation of a tetrapeptide, Val-Ala-Ala-Phe (VAAF), from Ag, Al,
      Au, Cu, Fe, and Ti foils, followed by protonation by protonated pyridine,
      revealed that the titanium foil provides the greatest signal. The importance of
      the laser power density was examined by desorbing a low MW polymer,
      polyisobutenyl succinic anhydride, at power densities ranging from 5.40 x 10(8)
      to 9.00 x 10(8) W/cm(2) at the backside of the foil. Higher laser power densities
      resulted in greater signals and an improved distribution for the higher molecular
      weight oligomers.

PMID- 16944896
TI  - Chromatographic alignment of ESI-LC-MS proteomics data sets by ordered bijective
      interpolated warping.
AB  - Mass spectrometry proteomics typically relies upon analyzing outcomes of single
      analyses; however, comparing raw data across multiple experiments should enhance
      both peptide/protein identification and quantitation. In the absence of
      convincing tandem MS identifications, comparing peptide quantities between
      experiments (or fractions) requires the chromatographic alignment of MS signals.
      An extension of dynamic time warping (DTW), termed ordered bijective interpolated
      warping (OBI-Warp), is presented and used to align a variety of electrospray
      ionization liquid chromatography mass spectrometry (ESI-LC-MS) proteomics data
      sets. An algorithm to produce a bijective (one-to-one) function from DTW output
      is coupled with piecewise cubic hermite interpolation to produce a smooth warping
      function. Data sets were chosen to represent a broad selection of ESI-LC-MS
      alignment cases. High confidence, overlapping tandem mass spectra are used as
      standards to optimize and compare alignment parameters. We determine that
      Pearson's correlation coefficient as a measure of spectra similarity outperforms
      covariance, dot product, and Euclidean distance in its ability to produce correct
      alignments with optimal and suboptimal alignment parameters. We demonstrate the
      importance of penalizing gaps for best alignments. Using optimized parameters, we
      show that OBI-Warp produces alignments consistent with time standards across
      these data sets. The source and executables are released under MIT style license
      at http://obi-warp.sourceforge.net/.

PMID- 16944897
TI  - The Genoa 2005 outbreak. Determination of putative palytoxin in Mediterranean
      Ostreopsis ovata by a new liquid chromatography tandem mass spectrometry method.
AB  - A new method for sensitive, specific, and direct determination of palytoxin is
      proposed herein. It is based on combination of reversed-phase liquid
      chromatography with mass spectrometry (LC-MS). The new method was set up on a
      turbo ion spray-triple quadrupole MS instrument operating in selected ion
      monitoring (SIM) and multiple reaction monitoring (MRM) acquisition modes
      (positive ions). The minimum detection levels for matrix-free toxin on column
      were thus estimated from the data to be 200 and 125 pg in SIM and MRM modes,
      respectively. Spiking experiments before and after extraction allowed us to
      assess limits of detection and quantitation for palytoxin in matrix, accuracy,
      and intraday and interday reproducibility of the method. The developed method was
      decisive for the analysis of a plankton sample collected along Genoa coasts in
      July 2005 when respiratory illness in people exposed to marine aerosols occurred.
      It is suggested that putative palytoxin was the causative agent responsible for
      patients' symptoms and demonstrated for the first time the presence of such a
      toxin in Italian waters.

PMID- 16944898
TI  - Sample preparation for MALDI mass spectrometry using an elastomeric device
      reversibly sealed on the MALDI target.
AB  - A new method for improving low-concentration sample recovery and reducing sample
      preparation steps in matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI MS) is presented. In the conventional approach, samples are
      typically desalted and/or concentrated with various techniques and deposited on
      the MALDI target as small droplets. In this work, we describe a new approach in
      which an elastomeric device is reversibly sealed on the MALDI target to form a
      multi-well plate with the MALDI target as the base of the plate. The new format
      allows a larger volume (5-200 microL) of samples to be deposited on each spot and
      a series of sample handling processes, including desalting and concentrating, to
      be performed directly on the MALDI target. Several advantages have been observed:
      (i) multiple sample transferring steps are avoided; (ii) recovery of low
      concentration peptides during sample preparation is improved using a novel
      desalting method that utilizes the hydrophobic surface of the elastomeric device;
      and (iii) sequence coverage of the peptide mass fingerprinting map is improved
      using a novel method in which proteins are immobilized on the hydrophobic surface
      of the elastomeric device for in-well trypsin digestion, followed by desalting
      and concentrating the digestion products in the same well.

PMID- 16944899
TI  - Comparison of two methods for obtaining quantitative mass concentrations from
      aerosol time-of-flight mass spectrometry measurements.
AB  - Aerosol time-of-flight mass spectrometry (ATOFMS) measurements provide continuous
      information on the aerodynamic size and chemical composition of individual
      particles. In this work, we compare two approaches for converting unscaled ATOFMS
      measurements into quantitative particle mass concentrations using (1) reference
      mass concentrations from a co-located micro-orifice uniform deposit impactor
      (MOUDI) with an accurate estimate of instrument busy time and (2) reference
      number concentrations from a co-located aerodynamic particle sizer (APS).
      Aerodynamic-diameter-dependent scaling factors are used for both methods to
      account for particle transmission efficiencies through the ATOFMS inlet. Scaling
      with APS data retains the high-resolution characteristics of the ambient aerosol
      because the scaling functions are specific for each hourly time period and
      account for a maximum in the ATOFMS transmission efficiency curve for larger
      sized particles. Scaled mass concentrations obtained from both methods are
      compared with co-located PM(2.5) measurements for evaluation purposes. When
      compared against mass concentrations from a beta attenuation monitor (BAM), the
      MOUDI-scaled ATOFMS mass concentrations show correlations of 0.79 at Fresno, and
      the APS-scaled results show correlations of 0.91 at Angiola. Applying composition
      dependent density corrections leads to a slope of nearly 1 with 0 intercept
      between the APS-scaled absolute mass concentration values and BAM mass
      measurements. This paper provides details on the methodologies used to convert
      ATOFMS data into continuous, quantitative, and size-resolved mass concentrations
      that will ultimately be used to provide a quantitative estimate of the number and
      mass concentrations of particles from different sources.

PMID- 16944900
TI  - Comprehensive interpretation of gel electrophoresis data.
AB  - From temperature analysis of polyacrylamide gel electrophoresis data for rigid
      rod DNA analytes, it is proposed that an entropic force term is responsible for
      the discrepancy between Ogston-Morris-Rodbard-Chrambach model predictions and
      experimental results. This entropic force originates from reduction of the
      orientational freedom of anisotropic analytes in small pores of polyacrylamide
      gels. Time-dependent fluorescence anisotropy decay measurements confirm that,
      even in the absence of an external field, orientation of anisotropic analytes is
      restricted in polyacrylamide gels. A new comprehensive model is proposed that
      takes this effect into consideration. Predictions based on this model are found
      to compare favorably with experimental data for linear and three-arm
      asymmetrically branched rigid-rod DNA analytes covering a broad range of
      molecular aspect ratios and sizes. A new length scale is also proposed for
      describing the effect of analyte topology on electrophoretic mobility. This
      length scale reduces to the analyte radius of gyration in the limiting cases of
      spherically symmetric and linear rigid-rod species. Based on these results, a
      general approach is proposed for interpreting gel electrophoresis data of charged
      analytes possessing simple and complex topologies.

PMID- 16944901
TI  - Imprinted polymeric materials. Insight into the nature of prepolymerization
      complexes of quercetin imprinted polymers.
AB  - Molecular imprinting techniques have proved to be a highly accessible method for
      producing molecule-specific recognition materials for a variety of applications,
      ranging from sensing to catalysis and separations. In noncovalent imprinting, it
      is anticipated that polymerizable complexes are created in the prepolymerization
      solution via self-assembly of functional monomers and template molecules
      resulting from inherent chemical complementarity, which will ideally form binding
      sites within the cross-linked matrix after polymerization. On the basis of 1H NMR
      data and X-ray crystallographic evidence, we now infer a more important role for
      template self-association for the recognition properties of quercetin-imprinted
      polymers. While directly applicable to fundamental understanding of the molecular
      imprinting mechanism of this polyphenol, on a more generic scale, this work also
      demonstrates the utility of this strategy toward analyzing complex noncovalent
      interaction mechanisms between small molecules. These interactions are of
      particular interest for quercetin and other members of the flavone/flavonoid
      class of compounds, which are radical-scavenging polyphenols of substantial
      interest to biomedicine.

PMID- 16944902
TI  - Domain size-induced heterogeneity as performance limitation of small-domain
      monolithic columns and other LC support types.
AB  - We have computed the band broadening and the flow resistance in a series of
      apparently self-similar porous LC support structures, all having the same mean
      geometric ratios and external porosity, but with a decreasing scale and disturbed
      by a scale-independent variance on the size and position of the porous solid zone
      elements. The study shows in a general and qualitative way that each type of LC
      support that is produced using a manufacturing process displaying a fixed (i.e.,
      domain-size independent) variance on the size and position of the produced solid
      zone elements will eventually encounter a limit beyond which a further reduction
      of the domain size can no longer be expected to yield a significant gain in
      separation speed. This is currently observed in practice for silica monoliths and
      could also compromise the performance of photolithographically etched columns.

PMID- 16944903
TI  - Automated identification and quantification of glycerophospholipid molecular
      species by multiple precursor ion scanning.
AB  - We report a method for the identification and quantification of
      glycerophospholipid molecular species that is based on the simultaneous automated
      acquisition and processing of 41 precursor ion spectra, specific for acyl anions
      of common fatty acids moieties and several lipid class-specific fragment ions.
      Absolute quantification of identified species was linear within a concentration
      range of 10 nM-100 microM and was achieved by spiking into total lipid extracts a
      set of synthetic lipid standards with diheptadecanoyl (17:0/17:0) fatty acid
      moieties, representing six common classes of glycerophospholipids. The automated
      analysis of total lipid extracts was powered by a robotic nanoflow ion source and
      produced currently the most detailed description of the glycerophospholipidome.

PMID- 16944904
TI  - Numeric simulation of heat transfer and electrokinetic flow in an electroosmosis
      based continuous flow PCR chip.
AB  - Precise design and operational control of the polymerase chain reaction process
      is key to the performance of on-chip DNA analysis. This research is dedicated to
      understanding the fluid flow and heat transfer mechanisms occurring in continuous
      flow PCR chips from the engineering point of view. In this work, a 3-dimensional
      model was developed to simulate the electrical potential field, the flow field,
      and the temperature field in an electroosmosis-based continuous flow PCR chip. On
      the basis of the simultaneous solution to this model, the effects of the
      channel/chip size, the chip material, and the applied voltage difference on the
      temperature distribution and control are discussed in detail. The importance of
      each heat transfer mechanism for different situations is also discussed. It was
      found that if a larger chip thickness or a material with a lower heat
      conductivity was used, the temperature in the microfluidic PCR chip would
      decrease dramatically. The effects of the applied electrical field strength and
      flow velocity on the temperature distribution, however, are negligible for
      microchannels with a small cross-sectional area. With bigger channels, the flow
      direction will affect the temperature distribution in the channel because heat
      convection will dominate heat transfer.

PMID- 16944905
TI  - Continuous flow thermal cycler microchip for DNA cycle sequencing.
AB  - We report here on the use of a polymer-based continuous flow thermal cycler
      (CFTC) microchip for Sanger cycle sequencing using dye terminator chemistry. The
      CFTC chip consisted of a 20-loop spiral microfluidic channel hot-embossed into
      polycarbonate (PC) that had three well-defined temperature zones poised at 95,
      55, and 60 degrees C for denaturation, renaturation, and DNA extension,
      respectively. The sequencing cocktail was hydrodynamically pumped through the
      microreactor channel at different linear velocities ranging from 1 to 12 mm/s. At
      a linear velocity of 4 mm/s resulting in a 36-s extension time, a read length of
      >600 bp could be obtained in a total reaction time of 14.6 min. Further increases
      in the flow rate resulted in a reduction in the total reaction time but also
      produced a decrease in the sequencing read length. The CFTC chip could be reused
      for subsequent sequencing runs (>30) with negligible amounts of carryover
      contamination or degradation in the sequencing read length. The CFTC microchip
      was subsequently coupled to a solid-phase reversible immobilization (SPRI)
      microchip made from PC for purification of the DNA sequencing ladders (i.e.,
      removal of excess dye-labeled dideoxynucleotides, DNA template, and salts) prior
      to gel electrophoresis. Coupling of the CFTC chip to the SPRI microchip showed
      read lengths similar to that obtained from benchtop instruments but did not
      require manual manipulation of the cycle sequencing reactions following
      amplification.

PMID- 16944906
TI  - In vivo detection of gold-imidazole self-assembly complexes: NIR-SERS signal
      reporters.
AB  - Here we report in vitro and in vivo detection of self-assembled Au-imidazole by
      using near-infrared surface-enhanced Raman scattering (NIR-SERS). In vivo, the Au
      imidazole structures were administered into tumor-bearing mice and detected
      noninvasively. The self-assembled Au-imidazole complexes were generated by the
      adsorption of imidazole molecules onto Au nanoparticles (NP) and were then
      characterized as aqueous suspensions by using NIR-SERS, angle-dependent light
      scattering with fractal dimension analysis, and visible extinction spectroscopy.
      The structure and optical activity was sensitive to imidazole concentration and
      Au NP size. Specifically, the Au-imidazole assemblies formed at lower imidazole
      concentrations had the lowest fractal dimension (D(f) = 1.2) and the largest
      Raman enhancement factors for the dominant NIR-SERS feature, a ring-breathing
      vibrational mode at 954 cm(-1). Changes in elastic scattering intensity, fractal
      dimension, and surface plasmon absorption were observed with increasing imidazole
      concentration. The Raman enhancement factor was also found to range between 10(6)
      and 10(9) with different primary Au nanoparticle sizes. For the higher
      enhancement factor systems, NIR-SERS detection of Au-imidazole was performed with
      data acquisitions time of only 5 s. The largest enhancement was observed for the
      954-cm(-1) feature at an imidazole concentration of 1.9 microM when coupled to 54
      nm-diameter Au NPs (the largest NP tested). Finally, we show the first
      demonstration of in vivo, noninvasive, and real-time SERS detection.

PMID- 16944907
TI  - Enhanced fluorescence of Cy5-labeled DNA tethered to silver island films:
      fluorescence images and time-resolved studies using single-molecule spectroscopy.
AB  - Methods that increase the total emission per fluorophore would provide increased
      sensitivity and a wider dynamic range for chemical analysis, medical diagnostics,
      and in vivo molecular imaging. The use of fluorophore-metal interactions has the
      potential to dramatically increase the detectability of single fluorophores for
      bioanalytical monitoring. The fabrication and single-molecule analysis of
      fluorophore-labeled DNA molecules tethered to silver island films are described
      in this article. The single-molecule spectroscopic method reveals some insightful
      information on the behaviors of single molecules, rather than an ensemble of
      molecules. Analysis of fluorescence images, intensity profiles, total emitted
      photons, and lifetime distributions reveals some of sample heterogeneities.
      Investigations of time-dependent emission characteristics of single molecules
      indicate that the total number of emitted photons on the silvered surface is more
      than 10 times greater than on free labeled DNA molecules on a glass substrate. In
      addition, time-correlated single-photon counting results reveal the reduced
      lifetimes of single molecules tethered to silver island films.

PMID- 16944909
TI  - Single column trapping/separation and chemiluminescence detection for on-site
      measurement of methyl mercaptan and dimethyl sulfide.
AB  - A simple, automated method for the measurement of methyl mercaptan (CH3SH) and
      dimethyl sulfide (DMS) has been investigated. These two sulfur gases have strong
      and unpleasant odors. The collection and separation are performed in sequence
      with a single short column packed with silica gel powder. CH3SH and DMS are
      separated according to their desorption temperatures and introduced into a
      chemiluminescence cell in this order. These two gases emit strong
      chemiluminescence by reaction with ozone. The calibration curves obtained are
      linear, which is superior to flame photometric detection of these substances. The
      whole system, including a small cylinder for the carrier nitrogen, can be set in
      a portable box. The instrument is applicable to breath odor analysis, and
      automated measurement of room air can also be performed. In toilet air analysis,
      it was observed that levels of the sulfur gases increased after dark. With this
      instrument, sulfur gases at a ppbv level are successfully measured by a simple
      procedure without much interference.

PMID- 16944908
TI  - Quantitative intracellular molecular profiling using a one-dimensional flow
      system.
AB  - We report on the development of one-dimensional microfluidic bead arrays for
      rapid and quantitative molecular profiling of human cancer cells. This new
      bioanalytical platform integrates the rapid binding kinetics of suspension bead
      carriers, the multiplexing and encoding capabilities of gene/protein chips, and
      the liquid handling advantages of microfluidic devices. Using antibody-conjugated
      beads in a two-site "sandwich" format, we demonstrate that the proteomic contents
      of as few as 56 human lung epithelial cancer cells can be determined with high
      sensitivity and specificity. The results indicate that each cell contains
      approximately 6 x 10(5) copies of the tumor suppressor protein P53. We have
      further examined the expression changes of P53, c-Myc, and beta-Actin as a
      function of anticancer drug treatment and have validated these changes by using
      Western blotting. This ability to quantitatively analyze normal and diseased
      cells raises new possibilities in studying cancer heterogeneity and circulating
      tumor cells.

PMID- 16944910
TI  - Ultrasound-promoted cold vapor generation in the presence of formic acid for
      determination of mercury by atomic absorption spectrometry.
AB  - A new cold vapor technique within the context of green chemistry is described for
      determination of mercury in liquid samples following high-intensity
      ultrasonication. Volatile Hg evolved in a sonoreactor without the use of a
      chemical reducing agent is carried to a quartz cell kept at room temperature for
      measurement of the atomic absorption. The mechanism involved lies in the
      reduction of Hg(II) to Hg(0) by reducing gases formed upon sonication and
      subsequent volatilization of Hg(0) due to the degassing effect caused by the
      cavitation phenomenon. Addition of a low molecular weight organic acid such as
      formic acid favors the process, but vapor generation also occurs from Hg
      solutions in ultrapure water. The detection limit of Hg was 0.1 microg/L, and the
      repeatability, expressed as relative standard deviation, was 4.4% (peak height).
      Addition of small amounts of oxidizing substances such as the permanganate or
      dichromate anions completely suppressed the formation of Hg(0), which confirms
      the above mechanism. Effect of other factors such as ultrasound irradiation time,
      ultrasound amplitude, and the presence of concomitants are also investigated.
      Some complexing anions such as chloride favored the stabilization of Hg(II) in
      solution, hence causing an interference effect on the ultrasound-assisted
      reduction/volatilization process.

PMID- 16944912
TI  - Monitoring and kinetics study of a single particle on a simple microfluidic chip.
AB  - A single-channel poly(dimethylsiloxane) microchip was developed for the
      desorption process monitoring and kinetics studies of a single particle. The
      microchannel consisting of a narrow section following a relatively wide part
      enabled particle introduction, transfer, and location. A microinfusion pump was
      employed to delivery eluting solution at a precise rate. Once the particle
      contacted with the eluting solution, the solute transferred from particle into
      eluting solution and would be detected by laser-induced fluorescence or a
      chemiluminescence detector. Desorption process of a single particle was
      sensitively monitored. Depending on the desorption curves obtained, kinetics
      studies were carried out. The sediment desorption process analyses of single
      resin particles and single active carbon particles were performed.

PMID- 16944911
TI  - Use of peptide retention time prediction for protein identification by off-line
      reversed-phase HPLC-MALDI MS/MS.
AB  - A new algorithm, sequence-specific retention calculator, was developed to predict
      retention time of tryptic peptides during RP HPLC fractionation on C18, 300-A
      pore size columns. Correlations of up to approximately 0.98 R2 value were
      obtained for a test library of approximately 2000 peptides and approximately 0.95
      0.97 for a variety of real samples. The algorithm was applied in conjunction with
      an exclusion protocol based on mass (15 ppm tolerance) and retention time (2-min
      tolerance for 0.66% acetonitrile/min gradient), MART criteria to significantly
      reduce the instrument time required for complete MS/MS analysis of a digest
      separated by RP HPLC. This was confirmed by reanalyzing the set of HPLC-MALDI
      MS/MS data with no loss in protein identifications, despite the number of
      virtually executed MS/MS analyses being decreased by 57%.

PMID- 16944913
TI  - Chemical-induced unfolding of cofactor-free protein monitored by
      electrochemistry.
AB  - Protein folding has been studied extensively with an aim to better understanding
      of the relationship between protein sequence, structure, and function. A large
      variety of techniques have been developed and utilized to probe protein
      conformation and folding/unfolding transition. In this report, electrochemical
      monitoring of urea-induced unfolding of a large cofactor-free protein, bovine
      serum albumin (BSA), is described. Enhanced electrochemical oxidation of tyrosine
      and tryptophan in free amino acids and in BSA was achieved on an indium tin oxide
      electrode by using an electron mediator, Os(bpy)2dppz (bpy = 2,2'-bipyridine,
      dppz = dipyrido[3,2-a:2',3'-c]phenazine). The oxidation current was used as a
      signal reporter in the monitoring of urea-induced BSA denaturation. At high urea
      concentrations, the electrochemical signal increased by 3-fold relative to the
      native protein. The increase is attributed to the closer contact between the
      oxidizable residues in the unfolded BSA and Os(bpy)2dppz. The degree of unfolding
      assessed by electrochemistry correlates well with the established fluorescence
      technique in the range of 0-10 M urea. The method can be used to investigate the
      unfolding process of other cofactor-free proteins.

PMID- 16944914
TI  - Silver nanocrystal-modified silicon nanowires as substrates for surface-enhanced
      Raman and hyper-Raman scattering.
AB  - Metal catalyzed, CVD-grown silicon nanowires decorated by chemical assembly of
      closely spaced Ag nanocrystals were modified with the well-known "silver mirror"
      reaction and investigated as substrates for surface-enhanced Raman (SERS) and
      hyper-Raman (SEHRS) spectroscopy. Four chromophores were examined: Rhodamine 6G,
      crystal violet, a cyanine dye, and a cationic donor-acceptor substituted
      stilbene. After soaking the substrates overnight in 10(-4) M aqueous chromophore
      solutions, all four chromophores gave good-quality SERS spectra in < or =60 s
      using <1 microW of 458-nm cw laser power, and SEHRS spectra are obtained in < or
      =120 s using <1 mW of mode-locked 916-nm laser power. Results from this substrate
      are compared with those on colloidal silver nanoparticles deposited as a film, as
      well as surfaces grown by the silver mirror reaction.

PMID- 16944917
TI  - Peptidomics for cancer diagnosis: present and future.
AB  - Analysis of peptides in biological fluids by mass spectrometry holds promise of
      providing diagnostic and prognostic information for cancer and other diseases.
      Before this technology is used clinically, it is important to understand its
      advantages and limitations. These are summarized, along with proposals, on how to
      proceed in the future.

PMID- 16944918
TI  - Glutamine-binding protein from Escherichia coli specifically binds a wheat
      gliadin peptide. 2. Resonance energy transfer studies suggest a new sensing
      approach for an easy detection of wheat gliadin.
AB  - In this work is presented the first attempt to develop a fluorescence assay for
      detection of traces of gluten in food by utilizing the recombinant glutamine
      binding protein (GlnBP) from E. coli. We found that GlnBP specifically binds the
      sequence of amino acids present both in gliadin and other prolamines classified
      as toxic for celiac patients. Affinity chromatography experiments together with
      mass spectrometry experiments demonstrated that GlnBP can bind the following
      amino acid sequence XXQPQPQQQQQQQQQQQQL. Sequence alignment experiments pointed
      out that this sequence is exclusively representative of the gliadin and the other
      prolamines considered toxic for celiac patients. These findings suggest the
      development of a competitive resonance energy transfer (RET) assay for an easy
      and rapid detection of this sequence in raw and cooked food.

PMID- 16944919
TI  - Selective disulfide bond cleavage in gold(I) cationized polypeptide ions formed
      via gas-phase ion/ion cation switching.
AB  - Gaseous multiply protonated disulfide-linked peptides have been subjected to
      reactions with AuCl2(-) ions to explore the possibility of effecting cation
      switching of Au+ for two protons and to determine whether cationization by Au+
      ions affords selective dissociation of disulfide linkages. The incorporation of
      Au+ into several model disulfide-linked peptides proved to be straightforward.
      The primary ion/ion reaction channels were proton transfer, which does not lead
      to Au+ incorporation, and attachment of AuCl2(-) ions to the polypeptide cation,
      which does incorporate Au+. Fragmentation of the attachment product, the extent
      of which varied with peptide and charge state, led to losses of one or more
      molecules of HCl and, to some extent, cleavage of polypeptides at the disulfide
      linkage into its two constituent chains. Collisional activation of the intact
      metal-ion-incorporated peptides showed cleavage of the disulfide linkage to be a
      major, and in some cases exclusive, process. Cations with protons as the only
      cationizing agents showed only small contributions from cleavage of the disulfide
      linkage. These results indicate that Au+ incorporation into a disulfide-linked
      polypeptide ion is a promising way to effect selective dissociation of disulfide
      bonds. Cation switching via ion/ion reactions is a convenient means for
      incorporating gold and is attractive because it avoids the requirement of adding
      metal salts to the analyte solution.

PMID- 16944920
TI  - An integrated proteomic workflow for two-dimensional differential gel
      electrophoresis and robotic spot picking.
AB  - New technologies have advanced the field of proteomics, and a number of companies
      have developed innovative platforms to drive this research. However, significant
      challenges are often encountered when trying to integrate complementary
      technologies from multiple manufacturers. We have developed a software and
      hardware solution to integrate the Ettan two-dimensional difference gel
      electrophoresis (2-D DIGE) system (GE Healthcare) with the Investigator ProPic
      spot picking robot (Genomic Solutions). We have analyzed protein sample
      preparations from bacterial and mammalian sources to demonstrate a new workflow
      with increased throughput for gel-based proteomics.

PMID- 16944921
TI  - Venom proteomes of closely related Sistrurus rattlesnakes with divergent diets.
AB  - The protein composition of the venoms of the three subspecies of Sistrurus
      catenatus (S. c. catenatus, tergeminus, and edwardsii) and a basal species,
      Sistrurus miliarius barbouri, were analyzed by RP-HPLC, N-terminal sequencing,
      MALDI-TOF peptide mass fingerprinting, and CID-MS/MS. The venoms of the four
      Sistrurus taxa contain proteins from 11 families. The protein family profile and
      the relative abundance of each protein group in the different venoms are not
      conserved. Myotoxins and 2-chain PLA2s were detected only in S.c. catenatus and
      S.c. tergeminus, whereas C-type BPP and Kunitz-type inhibitors were exclusively
      found in S.c. edwardsii and Sistrurus miliarius barbouri. Among major protein
      families, taxa were most similar in their metalloproteases (protein similarity
      coefficient value: 34%) and most divergent in PLA2s (12%), with values for
      disintegrins and serine proteases lying between these extremes (25 and 20%,
      respectively). The patterns of venom diversity points to either a gain in
      complexity in S. catenatus taxa or a loss of venom diversity occurring early on
      in the evolution of the group involving the lineage connecting S. milarius to the
      other taxa. The high degree of differentiation in the venom proteome among
      recently evolved congeneric taxa emphasizes the uniqueness of the venom
      composition of even closely related species that have different diets.
      Comparative proteomic analysis of Sistrurus venoms provides a comprehensive
      catalog of secreted proteins, which may contribute to a deeper understanding of
      the biology and ecology of these North American snakes and may also serve as a
      starting point for studying structure-function correlations of individual toxins.

PMID- 16944922
TI  - Starvation induces phase-specific changes in the proteome of mouse small
      intestine.
AB  - Food deprivation results in metabolic, structural, and functional changes in the
      small intestine that influences gut mucosal integrity, epithelial cell
      proliferation, mucin synthesis, and other processes. The underlying mechanisms
      are still unclear, which lead to the study of molecular effects of short-term and
      long-term starvation in the intestine of mice. A comparative proteomics approach,
      combining two-dimensional gel electrophoresis with matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry, was used to identify
      intestinal proteins whose expression is changed under different starvation
      conditions (0, 12, 24, and 72 h). In total, the expression levels of 80 protein
      spots changed significantly between the different groups. The results demonstrate
      that after 12 h of starvation, mainly proteins involved in glycolysis and energy
      metabolism show decreased expression levels. Starvation for 24 h results in a
      down-regulation of proteins involved in protein synthesis and amino acid
      metabolism. Simultaneously, proteins with a protective role, e.g., reg I and II,
      glutathione peroxidase 3, and carbonic anhydrase 3, are clearly up-regulated. The
      last starvation phase (72 h) is characterized by increased ezrin expression,
      which may enhance villus morphogenesis critical for survival. Together, these
      results provide novel insights in the intestinal starvation response and may
      contribute to improved nutritional support during conditions characterized by
      malnutrition.

PMID- 16944923
TI  - Interaction of zonula occludens-1 (ZO-1) with alpha-actinin-4: application of
      functional proteomics for identification of PDZ domain-associated proteins.
AB  - The use of recombinant "bait" proteins to capture protein-binding partners,
      followed by identification of protein interaction networks by mass spectrometry
      (MS), has gained popularity and widespread acceptance. We have developed an
      approach using recombinant PDZ protein interaction modules of the membrane
      associated guanylate kinase (MAGUK) protein zonula occludens-1 (ZO-1) to pull
      down and screen for proteins that interact with these modules via their PDZ
      domain binding motifs. Identification of proteins by MS of pull-down material was
      achieved using a vacuum-based chromatography sample preparation device designed
      for matrix-assisted laser desorption/ionization (MALDI) MS. MS analysis of
      tryptic fragments in pull-down material revealed a number of potential ZO-1
      interacting candidates, including the presence of peptides corresponding to the
      cortical membrane scaffolding protein alpha-actinin-4. Interaction of alpha
      actinin-4 with ZO-1 was confirmed by coimmunoprecipitation of these two proteins
      from cultured cells, as well as from brain, liver, and heart, and by immunoblot
      detection of alpha-actinin-4 after pull-down with the first PDZ domain of ZO-1.
      In contrast, the highly homologous alpha-actinin family member, alpha-actinin-1,
      displayed no association with ZO-1. Immunofluorescence showed colocalization of
      alpha-actinin-4 with ZO-1 in cultured HeLa and C6 glioma cells, as well as in a
      variety of tissues in vivo, including brain, heart, liver, and lung. This study
      demonstrates the utility of MS-based functional proteomics for identifying
      cellular components of the ZO-1 scaffolding network. Our finding of the
      interaction of ZO-1 with alpha-actinin-4 provides a mechanism for linking the
      known protein recruitment and signaling activities of ZO-1 with alpha-actinin-4
      associated plasma membrane proteins that have regulatory activities at cell-cell
      and cell-extracellular matrix contacts.

PMID- 16944924
TI  - Metabonomics study of intestinal fistulas based on ultraperformance liquid
      chromatography coupled with Q-TOF mass spectrometry (UPLC/Q-TOF MS).
AB  - Ultraperformance liquid chromatography coupled with Q-TOF mass spectrometry
      (UPLC/Q-TOF MS) is an effective and sensitive analytical tool. A UPLC/Q-TOF MS
      based metabonomics technique was employed to investigate sera from 40 patients
      with intestinal fistula and 17 healthy volunteers in an effort to find potential
      biomarkers of the disease and reveal their pathophysiological changes. After the
      UPLC/Q-TOF analysis, the retention time and m/z data pair for each peak were
      detected. Partial least squares discriminant analysis (PLS-DA) and coefficient of
      correlation analysis were used for marker selection and identification. According
      to the data, nine potential biomarkers were identified: glycochenodeoxycholic
      acid, glycocholic [corrected] acid, taurochenodexycholic acid, taurodeoxycholic
      acid, and two kinds of lysophosphatidyl choline (C16:0 and C18:2) were found with
      increased concentrations in the patients, and phenylalanine, tryptophan, and
      carnitine were found with decreased concentrations in the patients. The results
      suggested that a subclinical hepatic injury and abnormal metabolism of two
      essential amino acids (phenylalanine and tryptophan), and a key compound of fatty
      acid synthesis and beta-oxidation (carnitine), occurred in the fistula patients.
      This work demonstrates the utility of metabonomics as a top-down systems biology
      tool for understanding clinical problems.

PMID- 16944925
TI  - A novel approach of protein immobilization for protein chips using an oligo
      cysteine tag.
AB  - Protein chip technology is essential for high-throughput functional proteomics.
      We developed a novel protein tag consisting of five tandem cysteine repeats (Cys
      tag) at termini of proteins. The Cys-tag was designed to allow covalent
      attachment of proteins to the surface of a maleimide-modified, diamond-like,
      carbon-coated silicon substrate. As model proteins, we created an enhanced green
      fluorescent protein (EGFP) and an EGFP-stathmin fusion protein, both of which
      contained a Cys-tag. We also included an oligo-histidine tag to allow its
      purification by the use of Ni beads, and we expressed the protein in Escherichia
      coli. The purified Cys-tagged EGFP could be captured on the maleimide-coated
      substrate efficiently so that 50 pg of the fusion protein was detected by
      fluorescence, and as little as 5 pg was immunodetected by combination with
      enhanced chemiluminescence. This highly sensitive immunodetection may be due to
      the strong covalent binding of the Cys-tag to the substrate combined with
      efficient exposure of the protein to the surrounding solution. Thus, the Cys-tag
      should be useful for developing a novel protein printing method for protein chips
      that requires very low amounts of protein and can be used for high-performance
      analysis of protein-ligand interactions.

PMID- 16944926
TI  - Identification and confirmation of increased fibrinopeptide a serum protein
      levels in gastric cancer sera by magnet bead assisted MALDI-TOF mass
      spectrometry.
AB  - Gastric cancer is the second most common malignancy and prognosis remains dismal.
      The reasons for the poor prognosis are the lack of sensitive serum markers for
      early detection and screening of high-risk individuals as well as the limited
      treatment options in advanced cancer stages. Using MALDI-TOF mass spectrometry
      after prefractionation of sera with magnet hydrophobic C8 coated beads sera from
      14 patients with gastric cancer and 14 healthy controls mass spectra were
      generated. A peptide fragment was found to be highly elevated in cancer sera and
      was identified as fibrinopeptide A. To confirm proteome analysis of gastric
      cancer sera, we then screened a larger series of patients with gastric cancer (n
      = 99), high-risk individuals (n = 13) and normal controls (n = 111) for
      fibrinopeptide A serum levels. Interestingly, the mean logarithmic concentrations
      of serum fibrinopeptide A levels were significantly higher in cancer patients
      (mean 3.636 +/- 0.3738; p < 0.0001) and high-risk individuals (mean 3.569 +/-
      0.4722; p < 0.05) compared to normal controls (mean 3.303 +/- 0.4012). In
      contrast, we observed no association of fibrinopeptide A levels with tumor stage,
      tumor location, presence of regional or distant metastasis, and Lauren type of
      gastric cancer. In conclusion, MALDI-TOF mass spectrometry of prefractionated
      gastric cancer sera allows the identification of potential biomarkers that may
      lead to the development of serum based tests for screening of high-risk
      individuals.

PMID- 16944927
TI  - Creation of allotypic active sites during oxidative stress.
AB  - Oxidative stress is a factor in a series of diseases and aging, primarily through
      irreversible oxidative modification of proteins. A major question is how
      nonenzymatic oxidation has the specificity to impact cellular regulation. Here,
      we report the degree to which in vivo protein oxidation to the ketone and
      aldehyde level is random using yeast as a simple model system and hydrogen
      peroxide as an environmental oxidative stress agent. Among 415 affinity-selected
      proteins identified throughout the matrix of stressed cells, oxidation sites were
      found in 87, predominantly on lysine, arginine, proline, histidine, threonine,
      and methionine residues. In almost all cases, one to two specific oxidation sites
      on the exterior of proteins were identified using MS-derived sequence and
      publicly available 3-D structural data. This suggests that, when regulation or
      disease progression is mediated by protein oxidation, specific new "allotypic
      active sites" are being created in proteins that trigger the process.

PMID- 16944928
TI  - Proteins associated with disease and clinical course in pancreas cancer: a
      proteomic analysis of plasma in surgical patients.
AB  - New biomarkers for pancreas cancer are needed to improve its detection and
      management. We surveyed the plasma of patients undergoing surgical resection to
      identify proteins which change in abundance after complete resection of tumor.
      Using longitudinally collected specimens from surgical patients, we control for
      normal inter-individual variation which can confound cross-sectional analysis.
      Recent refinements in two-dimensional gel electrophoresis allowed us to quantify
      changes in low abundance plasma proteins with precision. To circumvent the
      traditional limitations of image analysis in comparing two-dimensional gels, we
      used fluorometric two-dimensional difference gel electrophoresis to resolve the
      proteins from pre- and post-surgical plasma from each patient on one physical
      gel. Furthermore, we increased the ability of our assay to detect low-abundance
      proteins by depleting the plasma of 12 high-abundance proteins with a multi
      affinity column. Informative protein spots from 20 plasma samples across 10
      patients were submitted for identification with mass-spectrometry. We identified
      a group of proteins which change consistently in plasma following complete
      resection of pancreas tumor. Furthermore, we identified proteins which correlate
      with post-surgical rapid recurrence of disease. With further identification and
      validation, the candidate biomarkers which we identify in this study may prove to
      be useful in the diagnosis, management and prognostication of patients with
      pancreas cancer.

PMID- 16944929
TI  - Protein bipartivity and essentiality in the yeast protein-protein interaction
      network.
AB  - Protein-protein interaction networks (PINs) are structured by means of a few
      highly connected proteins linked to a large number of less-connected ones.
      Essential proteins have been found to be more abundant among these highly
      connected proteins. Here we demonstrate that the likelihood that removal of a
      protein in a PIN will prove lethal to yeast correlates with the lack of
      bipartivity of the protein. A protein is bipartite if it can be partitioned in
      such a way that there are two groups of proteins with intergroup, but not
      intragroup, interactions. The abundance of essential proteins found among the
      least bipartite proteins clearly exceeds that found among the most connected
      ones. For instance, among the top 50 proteins ranked by their lack of bipartivity
      62% are essential proteins. However, this percentage is only 38% for proteins
      ranked according to their number of interactions. Protein bipartivity also
      surpasses another 5 measures of protein centrality in yeast PIN in identifying
      essential proteins and doubles the number of essential proteins selected at
      random. We propose a possible mechanism for the evolution of essential proteins
      in yeast PIN based on the duplication-divergence scheme. We conclude that a
      replica protein evolving from a nonbipartite target will also be nonbipartite
      with high probability. Consequently, these new replicas evolving from
      nonbipartite (essential) targets will with high probability be essential.

PMID- 16944930
TI  - Transgenomic metabolic interactions in a mouse disease model: interactions of
      Trichinella spiralis infection with dietary Lactobacillus paracasei
      supplementation.
AB  - Irritable Bowel Syndrome (IBS) is a common multifactorial intestinal disorder for
      which the aetiology remains largely undefined. Here, we have used a Trichinella
      spiralis (T. spiralis)-induced model of post-infective IBS, and the effects of
      probiotic bacteria on gut dysfunction have been investigated using a metabonomic
      strategy. A total of 44 mice were divided into four groups: an uninfected control
      group and three T. spiralis-infected groups, one as infected control and the two
      other groups subsequently treated with either Lactobacillus paracasei (L.
      paracasei) NCC2461 in spent culture medium (SCM) or with L. paracasei-free SCM.
      Plasma, jejunal wall and longitudinal myenteric muscle samples were collected at
      day 21 post-infection. An NMR-based metabonomic approach characterized that the
      plasma metabolic profile of T. spiralis-infected mice showed an increased energy
      metabolism (lactate, citrate, alanine), fat mobilization (acetoacetate, 3-D
      hydroxybutyrate, lipoproteins) and a disruption of amino acid metabolism due to
      increased protein breakdown, which were related to the intestinal
      hypercontractility. Increased levels of taurine, creatine and
      glycerophosphorylcholine in the jejunal muscles were associated with the muscular
      hypertrophy and disrupted jejunal functions. L. paracasei treatment normalized
      the muscular activity and the disturbed energy metabolism as evidenced by
      decreased glycogenesis and elevated lipid breakdown in comparison with untreated
      T. spiralis-infected mice. Changes in the levels of plasma metabolites
      (glutamine, lysine, methionine) that might relate to a modulation of
      immunological responses were also observed in the presence of the probiotic
      treatment. The work presented here suggests that probiotics may be beneficial in
      patients with IBS.

PMID- 16944931
TI  - Quantitative profiling of drug-associated proteomic alterations by combined 2
      nitrobenzenesulfenyl chloride (NBS) isotope labeling and 2DE/MS identification.
AB  - The identification of drug-responsive biomarkers in complex protein mixtures is
      an important goal of quantitative proteomics. Here, we describe a novel approach
      for identifying such drug-induced protein alterations, which combines 2
      nitrobenzenesulfenyl chloride (NBS) tryptophan labeling with two-dimensional gel
      electrophoresis (2DE)/mass spectrometry (MS). Lysates from drug-treated and
      control samples are labeled with light or heavy NBS moiety and separated on a
      common 2DE gel, and protein alterations are identified by MS through the
      differential intensity of paired NBS peptide peaks. Using NBS/2DE/MS, we profiled
      the proteomic alterations induced by tamoxifen (TAM) in the estrogen receptor
      (ER) positive MCF-7 breast cancer cell line. Of 88 protein spots that
      significantly changed upon TAM treatment, 44 spots representing 23 distinct
      protein species were successfully identified with NBS-paired peptides. Of these
      23 TAM-altered proteins, 16 (70%) have not been previously associated with TAM or
      ER activity. We found the NBS labeling procedure to be both technically and
      biologically reproducible, and the NBS/2DE/MS alterations exhibited good
      concordance with conventional 2DE differential protein quantitation, with
      discrepancies largely due to the comigration of distinct proteins in the regular
      2DE gels. To validate the NBS/2DE/MS results, we used immunoblotting to confirm
      GRP78, CK19, and PA2G4 as bona fide TAM-regulated proteins. Furthermore, we
      demonstrate that PA2G4 expression can serve as a novel prognostic factor for
      disease-free survival in two independent breast cancer patient cohorts. To our
      knowledge, this is the first report describing the proteomic changes in breast
      cancer cells induced by TAM, the most commonly used selective estrogen receptor
      modulator (SERM). Our results indicate that NBS/2DE/MS may represent a more
      reliable approach for cellular protein quantitation than conventional 2DE
      approaches.

PMID- 16944932
TI  - Identification of the SELDI ProteinChip human serum retentate by microcapillary
      liquid chromatography-tandem mass spectrometry.
AB  - Surface-enhanced laser desorption/ionization (SELDI) time-of-flight (TOF) mass
      spectrometry (MS) has been widely applied for conducting biomarker research with
      the goal of discovering patterns of proteins and/or peptides from biological
      samples that reflect disease status. Many diseases, ranging from cancers of the
      colon, breast, and prostate to Alzheimer's disease, have been studied through
      serum protein profiling using SELDI-based methods. Although the results from
      SELDI-based diagnostic studies have generated a great deal of excitement and
      skepticism alike, the basis of the molecular identities of the features that
      underpin the diagnostic potential of the mass spectra is still largely
      unexplored. A detailed investigation has been undertaken to identify the
      compliment of serum proteins that bind to the commonly used weak cation exchange
      (WCX-2) SELDI protein chip. Following incubation and washing of a standard serum
      sample on the WCX-2 sorbent, proteins were harvested, digested with trypsin,
      fractionated by strong cation exchange liquid chromatography (LC), and
      subsequently analyzed by microcapillary reversed-phase LC coupled online with an
      ion-trap mass spectrometer. This analysis resulted in the identification of 383
      unique proteins in the WCX-2 serum retentate. Among the proteins identified, 50
      (13%) are documented clinical biomarkers with 36 of these (72%) identified from
      multiple peptides.

PMID- 16944933
TI  - Proteomic analysis of effect of hyperthermia on spermatogenesis in adult male
      mice.
AB  - We characterized cellular and molecular mechanisms involved in spermatogenesis
      following short-term heat exposure of murine testis. For these studies, we
      utilized a proteomic approach with two-dimensional gel electrophoresis (2DE)
      analyses and mass spectroscopic identification of proteins with altered
      expression in mouse testes at different times after heat shock. We established a
      proteome reference map from 7-wk-old mouse testis linked to a federated proteome
      database. We used these tools to analyze quantitative variations in the tissue
      over a time course of 0.5, 2, 6, and 12 h following heat exposure. We separated
      108 protein spots expressed differentially between the heat shock tissues and the
      control mouse testes. Of these spots, we identified 36 by comparing with the
      control reference map. We then focused on the heterogeneous nuclear
      ribonucleoproteins (hnRNPs) and the chaperonins containing t-complex polypeptide
      1 (CCT). Further analysis in this heat-shocked model suggests numerous potential
      mechanisms for heat shock-induced spermatogenic disorder.

PMID- 16944934
TI  - Proteomic analysis of amniotic membrane prepared for human transplantation:
      characterization of proteins and clinical implications.
AB  - Amniotic membrane is commonly exploited in several surgical procedures. Despite a
      freeze preservation period, it is reported to retain wound healing, anti
      angiogenic, antiinflammatory and anti-scarring properties; however, little is
      known about the active protein content. 2-DE analysis of transplant-ready
      amniotic membrane (TRAM) was performed. The effects of preservation and
      processing on amnion proteome were investigated, and the major proteins in the
      TRAM characterized using mass spectrometry and immunoblotting. This identified a
      spectrum of proteins including thrombospondin, mimecan, BIG-H3, and integrin
      alpha 6. Preservation compromises cellular viability resulting in selective
      elution of soluble cellular proteins, leaving behind extracellular matrix
      associated and cell structural proteins. A number of key architectural proteins
      common to the architecture of the ocular surface were demonstrated in AM, which
      are involved in homeostasis and wound healing. Handling procedures alter the
      protein composition of amniotic membrane prepared for transplantation. Without
      standardization, there will be inter-membrane variation, which may compromise the
      desired therapeutic effect of transplant ready amniotic membrane.

PMID- 16944935
TI  - Phyloproteomics: what phylogenetic analysis reveals about serum proteomics.
AB  - Phyloproteomics is a novel analytical tool that solves the issue of comparability
      between proteomic analyses, utilizes a total spectrum-parsing algorithm, and
      produces biologically meaningful classification of specimens. Phyloproteomics
      employs two algorithms: a new parsing algorithm (UNIPAL) and a phylogenetic
      algorithm (MIX). By outgroup comparison, the parsing algorithm identifies novel
      or vanished MS peaks and peaks signifying up or down regulated proteins and
      scores them as derived or ancestral. The phylogenetic algorithm uses the latter
      scores to produce a biologically meaningful classification of the specimens.

PMID- 16944936
TI  - Optimized peptide separation and identification for mass spectrometry based
      proteomics via free-flow electrophoresis.
AB  - Multidimensional LC-MS based shotgun proteomics experiments at the peptide level
      have traditionally been carried out by ion exchange in the first dimension and
      reversed-phase liquid chromatography in the second. Recently, it has been shown
      that isoelectric focusing (IEF) is an interesting alternative approach to ion
      exchange separation of peptides in the first dimension. Here we present an
      improved protocol for peptide separation by continuous free-flow electrophoresis
      (FFE) as the first dimension in a two-dimensional peptide separation work flow.
      By the use of a flat pI gradient and a mannitol and urea based separation media
      we were able to perform high-throughput proteome analysis with improved
      interfacing between FFE and RPLC-MS/MS. The developed protocol was applied to a
      cytosolic fraction from Schneider S2 cells from Drosophila melanogaster,
      resulting in the identification of more than 10,000 unique peptides with high
      probability. To improve the accuracy of the peptide identification following FFE
      IEF we incorporated the pI information as an additional parameter into a
      statistical model for discrimination between correct and incorrect peptide
      assignments to MS/MS spectra.

PMID- 16944937
TI  - OmpW and OmpV are required for NaCl regulation in Photobacterium damsela.
AB  - Photobacterium damsela is a marine pathogen to both fish and human beings. The
      bacterium can shift between the ambient seawater and hosts, suggesting the
      existence of proteins rapidly responding to salt concentration. In the current
      study, proteomic methodologies were applied to screen the outer membrane proteins
      (OMPs) related to salt stress. OmpW and OmpV were determined in the response in
      this bacterium as OmpC and OmpF did in E. coli. Furthermore, the two genes were
      overexpressed in E. coli Top10F and complemented in V. paraheamolyticus mutants.
      The ability in salt-tolerance was elevated in the E. coli overexpressed OmpW and
      reduced in the cells overexpressed OmpV. These V. paraheamolyticus mutants could
      recover their response to environmental salt concentration when they were
      complemented by P. damsela OmpW and OmpV. These findings indicate that OmpW and
      OmpV are required for environmental salt regulation in P. damsela, in which OmpW
      and OmpV, respectively, elevate and reduce the ability in salinity-tolerance.

PMID- 16944938
TI  - Discovery and identification of potential biomarkers in a prospective study of
      chronic lymphoid malignancies using SELDI-TOF-MS.
AB  - The accurate diagnosis of the different forms of chronic mature B-cell
      lymphocytic malignancies is of primary importance to determine an appropriate and
      efficient treatment. Usually, the diagnosis is achieved by morphology and
      immunophenotyping. Nevertheless, the diagnostic tools available are not able to
      discriminate pathologies with variable evolution, or to classify some of them. To
      discover new biomarkers, we used peptide and protein profiling SELDI-TOF-MS, to
      analyze 39 chronic B-cell malignancies and 20 control serum samples. Markers of
      interest were subsequently identified and characterized. In the obtained SELDI-MS
      profiles, most of the differences were observed in three mass ranges (m/z = 13
      000; m/z = 9000; m/z < 2000). Identification of these biomarkers was achieved
      either by direct enrichment on the ProteinChip arrays followed by on-chip-MS/MS
      or by chromatographic fractionation, 1D-gel followed by nanoLC-MS/MS analysis. An
      increase of a sulfite form of transthyretin (13,841 Da) was observed in the
      patient group. A second set of markers at 8.6 and 8.9 kDa was identified as
      complement related fragment proteins, the C3a and C4a anaphylatoxins. In the low
      mass range, several peptides originating from N-terminal and C-terminal
      processing of the C3 alpha and C4 alpha chains were specifically observed in 38%
      of the patient sera, but in none of the control sera. This study emphasizes the
      usefulness of mass spectrometry studies in such malignancies.

PMID- 16944939
TI  - Protein cross-linking analysis using mass spectrometry, isotope-coded cross
      linkers, and integrated computational data processing.
AB  - Distance constraints in proteins and protein complexes provide invaluable
      information for calculation of 3D structures, identification of protein binding
      partners and localization of protein-protein contact sites. We have developed an
      integrative approach to identify and characterize such sites through the analysis
      of proteolytic products derived from proteins chemically cross-linked by
      isotopically coded cross-linkers using LC-MALDI tandem mass spectrometry and
      computer software. This method is specifically tailored toward the rapid analysis
      of low microgram amounts of proteins or multimeric protein complexes cross-linked
      with nonlabeled and deuterium-labeled bis-NHS ester cross-linking reagents (both
      commercially available and readily synthesized). Through labeling with [18O]water
      solvent and LC-MALDI analysis, the method further allows the possible distinction
      between Type 0 and Type 1 or Type 2 modified peptides (monolinks and looplinks or
      cross-links), although such a distinction is more readily made from analysis of
      tandem mass spectrometry data. When applied to the bacterial Colicin E7 DNAse/Im7
      heterodimeric protein complex, 23 cross-links were identified including six
      intersubunit cross-links, all between residues that are close in space when
      examined in the context of the X-ray structure of the heterodimer. In addition,
      cross-links were successfully identified in five single subunit proteins, beta
      lactoglobulin, cytochrome c, lysozyme, myoglobin, and ribonuclease A,
      establishing the generality of the approach.

PMID- 16944940
TI  - Rapid alteration of the phosphoproteome in the moss Physcomitrella patens after
      cytokinin treatment.
AB  - Cytokinin hormones are crucial regulators of a large number of processes in plant
      development. Recently, significant progress has been made toward the elucidation
      of the molecular details of cytokinin that has led to a model for signal
      transduction involving a phosphorylation cascade. However, the current knowledge
      of cytokinin action remains largely unknown and does not explain the different
      roles of this hormone. To gain further insights into this aspect of cytokinin
      action and the inducible phosphorelay, we have produced the first large-scale map
      of a phosphoproteome in the moss Physcomitrella patens. Using a protocol that we
      recently published (Heintz, D.; et al. Electrophoresis 2004, 25, 1149-1159) that
      combines IMAC, MALDI-TOF-MS, and LC-MS/MS, a total of 172 phosphopeptide
      sequences were obtained by a peptide de novo sequencing strategy. Specific P.
      patens EST and raw genomic databases were interrogated, and protein homology
      searches resulted in the identification of 112 proteins that were then classified
      into functional categories. In addition, the temporal dynamics of the
      phosphoproteome in response to cytokinin stimulation was studied at 2, 4, 6, and
      15 min after hormone addition. We identified 13 proteins that were not previously
      known targets of cytokinin action. Among the responsive proteins, some were
      involved in metabolism, and several proteins of unknown function were also
      identified. We have mapped the time course of their activation in response to
      cytokinin and discussed their hypothetical biological significance. Deciphering
      these early induced phosphorylation events has shown that the cytokinin effect
      can be rapid (few minutes), and the duration of this effect can be variable. Also
      phosphorylation events can be differentially regulated. Taken together our
      proteomic study provides an enriched look of the multistep phosphorelay system
      mediating cytokinin response and suggests the existence of a multidirectional
      interaction between cytokinin and numerous other pathways.

PMID- 16944941
TI  - Comparison of MS/MS methods for protein identification from 2D-PAGE.
AB  - We have compared the use of a low resolution MALDI-Ion Trap MS/MS and a high
      resolution ESI-TOF-MS/MS for the analysis of spots from 2D gels. The main
      criteria were speed and accuracy of protein identification. The results obtained
      using the MALDI-MS/MS system are comparable to those from the LC-MS/MS system in
      terms of accuracy, but less low-level proteins are identified while the time
      required for the analysis is dramatically reduced.

PMID- 16944942
TI  - Proteomic study of plasma from moderate hypercholesterolemic patients.
AB  - Proteomics is a technology to detect and identify several proteins and their
      isoforms in a single sample. We used proteomics to analyze modifications in the
      protein map of plasma after simvastatin treatment of moderate
      hypercholesterolemic patients. Plasma from hypercholesterolemic patients (n = 9)
      was compared before and after 12 weeks of simvastatin treatment (40 mg/day).
      Patients with similar cardiovascular risk factors were used as controls (CR
      group). By using two-dimensional electrophoresis and mass spectrometry, we
      identified the different protein isoforms. The plasma expression of three
      fibrinogen gamma chain isoforms (FGG) was enhanced, whereas the expression of two
      isoforms of the fibrinogen beta chain (FGB) was reduced in the
      hypercholesterolemic patients compared with the CR group. The expression of
      apolipoprotein A-IV and three haptoglobin isoforms was higher in
      hypercholesterolemic patients. Simvastatin treatment modified the plasma
      expression of FGG chain isoform 1, FGB chain isoforms 1 and 2, vitamin D binding
      protein isoform 3, apo A-IV, and haptoglobin isoform 2. The modification of FGG
      chain isoform 1 and FGB chain isoforms 1 and 2 was positively correlated with
      total plasma cholesterol level. Proteomic analysis of plasma may help to know
      more in depth the molecular mechanism modified by simvastatin treatment.

PMID- 16944943
TI  - Proteomic analysis of root meristems and the effects of acetohydroxyacid synthase
      inhibiting herbicides in the root of Medicago truncatula.
AB  - Quantitative proteome analyses of meristematic and nonmeristematic tissues from
      Medicago truncatula primary and lateral roots and meristem tissues from plants
      treated with acetohydroxyacid synthase-inhibiting herbicides were made. The
      accumulation of 81 protein spots changed in meristematic and nonmeristematic
      tissues and 51 protein spots showed significant changes in accumulation in
      herbicide-treated meristems. Identified proteins indicate two trends, (i)
      increased accumulation of cell division and redox-mediating proteins in meristems
      compared to nonmeristematic tissues and (ii) increased accumulation of
      pathogenesis-related and decreased accumulation of metabolic proteins in
      herbicide-treated roots.

PMID- 16944944
TI  - A proteomics approach to identify protein expression changes in rat liver
      following administration of 3,5,3'-triiodo-L-thyronine.
AB  - We analyzed whole cell protein content of rat liver following T3 administration.
      Fourteen differentially expressed proteins were unambiguously identified and were
      involved in substrates and lipid metabolism, energy metabolism, detoxification of
      cytotoxic products, calcium homeostasis, amino acid catabolism, and the urea
      cycle. This study represents the first systematic identification of T3-induced
      changes in liver protein expression profile and provides novel information at the
      molecular, cellular, and tissue level of T3 action.

PMID- 16944945
TI  - Multi-Q: a fully automated tool for multiplexed protein quantitation.
AB  - The iTRAQ labeling method combined with shotgun proteomic techniques represents a
      new dimension in multiplexed quantitation for relative protein expression
      measurement in different cell states. To expedite the analysis of vast amounts of
      spectral data, we present a fully automated software package, called Multi-Q, for
      multiplexed iTRAQ-based quantitation in protein profiling. Multi-Q is designed as
      a generic platform that can accommodate various input data formats from search
      engines and mass spectrometer manufacturers. To calculate peptide ratios, the
      software automatically processes iTRAQ's signature peaks, including peak
      detection, background subtraction, isotope correction, and normalization to
      remove systematic errors. Furthermore, Multi-Q allows users to define their own
      data-filtering thresholds based on semiempirical values or statistical models so
      that the computed results of fold changes in peptide ratios are statistically
      significant. This feature facilitates the use of Multi-Q with various instrument
      types with different dynamic ranges, which is an important aspect of iTRAQ
      analysis. The performance of Multi-Q is evaluated with a mixture of 10 standard
      proteins and human Jurkat T cells. The results are consistent with expected
      protein ratios and thus demonstrate the high accuracy, full automation, and high
      throughput capability of Multi-Q as a large-scale quantitation proteomics tool.
      These features allow rapid interpretation of output from large proteomic datasets
      without the need for manual validation. Executable Multi-Q files are available on
      Windows platform at http://ms.iis.sinica.edu.tw/Multi-Q/.

PMID- 16944946
TI  - Statistical analysis of membrane proteome expression changes in Saccharomyces
      cerevisiae.
AB  - We have devised an approach for analyzing shotgun proteomics datasets based on
      the normalized spectral abundance factor that can be used for quantitative
      proteomics analysis. Three biological replicates of samples enriched for plasma
      membranes were isolated from S. cerevisiae grown in 14N-rich media and 15N
      minimal media and analyzed via quantitative multidimensional protein
      identification technology. The natural log transformation of NSAF values from S.
      cerevisiae cells grown in 14N YPD media and 15N-minimal media had a normal
      distribution. The t-test analysis demonstrated 221 of 1316 proteins were
      significantly overexpressed in one or the other growth conditions with a p value
      <0.05. Notably, amino acid transporters were among the 14 membrane proteins that
      were significantly upregulated in cells grown in minimal media, and we
      functionally validated these increases in protein expression with radioisotope
      uptake assays for selected proteins.

PMID- 16944947
TI  - Semiautomated high-sensitivity profiling of human blood serum glycoproteins
      through lectin preconcentration and multidimensional chromatography/tandem mass
      spectrometry.
AB  - We describe an effective analytical approach to identify trace glycoproteins in a
      small volume of human serum. The system is based on automatable affinity
      enrichment through silica-based lectin microcolumns and a further separation of
      the retained glycoproteins on a reversed-phase liquid chromatography with
      superficially porous packing, operating at high temperature. The fractionated
      sample is further directed into a 96-well plate for trypsinization and LC-MS/MS
      analysis. Using a major-component depleted blood serum (16 microg total protein),
      we were able to identify 271 glycoproteins through this analytical system.

PMID- 16944948
TI  - Focused proteomics in post-mortem human spinal cord.
AB  - With a highly sensitive electrospray ionization-Fourier transform ion cyclotron
      resonance mass spectrometry (ESI-FTICR MS) system, proteins were identified in
      minimal amounts of spinal cord from patients with the neurodegenerative disease
      amyotrophic lateral sclerosis (ALS) and compared to proteins in spinal cord from
      control subjects. The results show 18 versus 16 significantly identified (p <
      0.05) proteins, respectively, all known to be found in the central nervous
      system. The most abundant protein in both groups was the glial fibrillary acidic
      protein, GFAP. Other proteins were, for example, hemoglobin alpha- and beta
      chain, myelin basic protein, thioredoxin, alpha enolase, and choline
      acetyltransferase. This study also includes the technique of laser
      microdissection in combination with pressure catapulting (LMPC) for the
      dissection of samples and specific neurons. Furthermore, complementary
      experiments with nanoLC-matrix assisted laser desorption ionization time-of
      flight tandem mass spectrometry (MALDI-TOF-TOF MS) confirmed the results of the
      ESI-FTICR MS screening and provided additional results of further identified
      proteins.

PMID- 16944949
TI  - Identification of 14-3-3epsilon substrates from embryonic murine brain.
AB  - Mice deficient in 14-3-3epsilon exhibit abnormal neuronal migration and die
      perinatally. We report here the first large-scale analysis of 14-3-3 interacting
      partners from primary animal tissue, identifying from embryonic murine brain 163
      14-3-3epsilon interacting proteins and 85 phosphorylation sites on these
      proteins. Phosphorylation of the deubiquitinating enzyme USP8 at serine 680 was
      found essential for its interaction with 14-3-3epsilon and for maintaining USP8
      in the cytosol.

PMID- 16944950
TI  - Investigating the dynamic nature of the interactions between nuclear proteins and
      histones upon DNA damage using an immobilized peptide chemical proteomics
      approach.
AB  - As a result of the complexity and dynamic range of the cellular proteome,
      including mutual interactions and interactions with other molecules, focused
      proteomic approaches are important to study subsets of physiologically important
      proteins. In one such approach, a small molecule or part of a protein is
      immobilized on a solid phase and used as bait to fish out interacting proteins
      from complex mixtures such as cellular lysates. Here, such a chemical proteomics
      experiment is presented to explore the range of proteins that interact with the N
      terminal tail of core histones. Therefore, a core histone consensus N-terminal
      tail (NTT) peptide was synthesized and immobilized on agarose. Interactions
      between histone NTTs and proteins are extremely important as they regulate
      chromatin structure, which is important in many DNA-related processes, like
      transcription and DNA repair. Induction of DNA damage, like DNA double strand
      breaks, is known to trigger chromatin remodeling events through interactions
      between histone NTTs and so-called histone chaperones. Therefore, we set out to
      investigate specific changes in interactions of nuclear proteins before and
      shortly after DNA double strand break induction. Over 700 proteins were found to
      bind specifically to the NTT peptide, which makes our study the most
      comprehensive proteomic survey of the broad spectrum of nuclear proteins
      interacting with the NTT of core histones in nucleosomes. Apart from a few
      exceptions, the abundance of the majority of NTT binding proteins was found to be
      unchanged following DNA damage. However, an in-depth analysis of protein
      phosphorylation (we detected more than 90 unique sites in about 60 proteins)
      revealed that the phosphorylation status of several proteins involved in
      chromatin remodeling changes upon DNA damage. We observed that in these
      differentially phosphorylated chaperones are part of closely interacting protein
      complexes involved in regulatory mechanisms at the crossroads of nucleosome
      assembly, DNA replication, transcription, and the early onset of DNA damage
      repair.

PMID- 16944951
TI  - Alterations in the mitochondrial proteome of adriamycin resistant MCF-7 breast
      cancer cells.
AB  - A 2D-gel based comparative proteomic analysis has been conducted of changes in
      mitochondrial protein abundances in MCF-7 human breast cancer cells selected for
      resistance to Adriamycin accompanied by verapamil. We identified and compared 156
      unique proteins from 184 spots. Eleven mitochondrial proteins were found with
      abundances altered more than 2-fold. Transcription was evaluated for two of
      these, using quantitative RT-PCR. Implications of the changes are considered with
      respect to drug resistance.

PMID- 16944952
TI  - Proteomic analysis of hypoxia/ischemia-induced alteration of cortical development
      and dopamine neurotransmission in neonatal rat.
AB  - Perinatal hypoxia/ischemia (HI) is a common cause of neurological deficits in
      children. Our goal was to elucidate the underlying mechanisms that contribute to
      the neurological sequelae of HI-induced brain injury. HI was induced by permanent
      ligation of the left carotid artery followed by 90 min of hypoxia (7.8% O2) in
      female P7 rats. A two-dimensional differential proteome analysis was used to
      assess changes in protein expression in cortex 2 h after HI. In total, 17
      proteins reflecting a 2-fold or higher perturbation of expression after HI as
      compared to sham-treated pups were identified by mass spectrometry. Of the
      altered proteins, 14-3-3epsilon and TUC-2, both playing an important role in the
      development of the central nervous system, decrease after HI, consistent with an
      early disturbance of cortical development. Also affected, DARPP-32 and alpha
      synuclein, two proteins important for dopamine neurotransmission, increased more
      than 2-fold 2 h after HI injury. The differential expression of these proteins
      was validated by individual Western blot assays. The expression of several
      metabolic enzymes and translational factors was also perturbed early after HI
      brain injury. These findings provide initial insights into the mechanisms
      underlying neurodegenerative events after HI and may allow for the rational
      design of therapeutic strategies that enhance neuronal adaptation and
      compensation after HI.

PMID- 16944954
TI  - Identification of protein networks associated with the PAK1-betaPIX-GIT1-paxillin
      signaling complex by mass spectrometry.
AB  - The process of cell motility involves coordinate signaling events among proteins
      associated in interactive integrin-linked networks. Mass spectrometric analysis
      of immunoprecipitation-derived protein mixtures have provided efficient means of
      identifying proteomes. In this study, we investigate strategies to enhance the
      detection of interactome proteins for the known signaling module: PAK1, betaPIX,
      GIT1, and paxillin. Our results indicate that near-endogenous expression levels
      of bait protein enhances the identification of associated proteins, and that
      phosphatase inhibition augments the detection of specific protein interactions.
      Following the analysis of a large pool of spectral data, we have identified and
      mapped clusters of proteins that either share common interactions among the four
      bait proteins of interest or are exclusive to single bait proteins. Taken
      together, these data indicate that biochemical manipulations can enhance the
      ability for LC-MS/MS to identify interactome proteins, and that qualitative
      screening of multiple samples leads to the compilation of proteins associated
      with a known plexus.

PMID- 16944953
TI  - Mass spectrometry reveals specific and global molecular transformations during
      viral infection.
AB  - Mass spectrometry analysis was used to target three different aspects of the
      viral infection process: the expression kinetics of viral proteins, changes in
      the expression levels of cellular proteins, and the changes in cellular
      metabolites in response to viral infection. The combination of these methods
      represents a new, more comprehensive approach to the study of viral infection
      revealing the complexity of these events within the infected cell. The proteins
      associated with measles virus (MV) infection of human HeLa cells were measured
      using a label-free approach. On the other hand, the regulation of cellular and
      Flock House Virus (FHV) proteins in response to FHV infection of Drosophila cells
      was monitored using stable isotope labeling. Three complementary techniques were
      used to monitor changes in viral protein expression in the cell and host protein
      expression. A total of 1500 host proteins was identified and quantified, of which
      over 200 proteins were either up- or down-regulated in response to viral
      infection, such as the up-regulation of the Drosophila apoptotic croquemort
      protein, and the down-regulation of proteins that inhibited cell death. These
      analyses also demonstrated the up-regulation of viral proteins functioning in
      replication, inhibition of RNA interference, viral assembly, and RNA
      encapsidation. Over 1000 unique metabolites were also observed with significant
      changes in over 30, such as the down-regulated cellular phospholipids possibly
      reflecting the initial events in cell death and viral release. Overall, the
      cellular transformation that occurs upon viral infection is a process involving
      hundreds of proteins and metabolites, many of which are structurally and
      functionally uncharacterized.

PMID- 16944955
TI  - Identification of marker proteins for the adulteration of meat products with
      soybean proteins by multidimensional liquid chromatography-tandem mass
      spectrometry.
AB  - Soybean proteins are frequently added to processed meat products for economic
      reasons and to improve their functional properties. Monitoring of the addition of
      soybean protein to meat products is of high interest due to the existence of
      regulations forbidding or limiting the amount of soybean proteins that can be
      added during the processing of meat products. We have used chromatographic
      prefractionation on the protein level by perfusion liquid chromatography to
      isolate peaks of interest from extracts of soybean protein isolate (SPI) and of
      meat products containing SPI. After enzymatic digestion using trypsin, the
      collected fractions were analyzed by nanoflow liquid chromatography-tandem mass
      spectrometry. Several variants and subunits of the major seed proteins, glycinin
      and beta-conglycinin, were identified in SPI, along with two other proteins. In
      soybean-protein-containing meat samples, different glycinin A subunits could be
      identified from the peak discriminating between samples with and without soybean
      proteins added. Among those, glycinin G4 subunit A4 was consistently found in all
      samples. Consequently, this protein (subunit) can be used as a target for new
      analytical techniques in the course of identifying the addition of soybean
      protein to meat products.

PMID- 16944956
TI  - Zirconium phosphonate-modified porous silicon for highly specific capture of
      phosphopeptides and MALDI-TOF MS analysis.
AB  - Phosphorylation is one of the most important post-translational modifications of
      proteins, which modulates a wide range of biological functions and activity of
      proteins. The analysis of phosphopeptides is still one of the most challenging
      tasks in proteomics research by mass spectrometry. In this study, a novel
      phosphopeptide enrichment approach based on the strong interaction of zirconium
      phosphonate (ZrP) modified surface with phosphopeptides has been developed. ZrP
      modified porous silicon (ZrP-pSi) wafer was prepared to specifically capture the
      phosphopeptides from complex peptide mixtures, and then the captured
      phosphopeptides were analyzed by MALDI-TOF MS by directly placing the wafer on a
      MALDI target. The phosphopeptide enrichment and MALDI analysis were both
      performed on the ZrP-pSi wafer which significantly reduced the sample loss and
      simplified the analytical procedures. The prepared ZrP-pSi wafer has been
      successfully applied for the enrichment of phosphopeptides from the tryptic
      digest of standard phosphoproteins beta-casein and alpha-casein. The excellent
      selectivity of this approach was demonstrated by analyzing phosphopeptides in the
      digest mixture of beta-casein and bovine serum albumin with molar ratio of 1:100.
      High detection sensitivity has been achieved for the analysis of the
      phosphopeptides from tryptic digestion of 2 fmol beta-casein on the ZrP-pSi
      surface.

PMID- 16944957
TI  - Proteome-wide characterization of N-glycosylation events by diagonal
      chromatography.
AB  - A procedure to map N-glycosylation sites is presented here. It can be applied to
      purified proteins as well as to highly complex mixtures. The method exploits
      deglycosylation by PNGase F in a diagonal, reverse-phase chromatographic setup.
      When applied to 10 microL of mouse serum, affinity-depleted for its three most
      abundant components, 117 known or predicted sites were mapped in addition to 10
      novel sites. Several sites were detected on soluble membrane or receptor
      components. Our method furthermore senses the nature of glycan structures and can
      detect differential glycosylation on a given site. These properties--high
      sensitivity and dependence on glycan imprinting--can be exploited for glycan
      biomarker analysis.

PMID- 16944958
TI  - Rapid validation of protein identifications with the borderline statistical
      confidence via de novo sequencing and MS BLAST searches.
AB  - Protein identifications with the borderline statistical confidence are typically
      produced by matching a few marginal quality MS/MS spectra to database peptide
      sequences and represent a significant bottleneck in the reliable and reproducible
      characterization of proteomes. Here, we present a method for rapid validation of
      borderline hits that circumvents the need in, often biased, manual inspection of
      raw MS/MS spectra. The approach takes advantage of the independent interpretation
      of corresponding MS/MS spectra by PepNovo de novo sequencing software followed by
      mass spectrometry-driven BLAST (MS BLAST) sequence-similarity database searches
      that utilize all partially inaccurate, degenerate and redundant candidate peptide
      sequences. In a case study involving the identification of more than 180
      Caenorhabditis elegans proteins by nanoLC-MS/MS analysis on a linear ion trap LTQ
      mass spectrometer, the approach enabled rapid assignment (confirmation or
      rejection) of more than 70% of Mascot hits of borderline statistical confidence.

PMID- 16944959
TI  - Proteomic and computational analysis of secreted proteins with type I signal
      peptides from the Antarctic archaeon Methanococcoides burtonii.
AB  - LC-MS/MS was used to identify secreted proteins in the Antarctic archaeon
      Methanococcoides burtonii. Seven proteins possessing a classical class 1 signal
      peptide were identified in the supernatant from cultures grown at 4 and 23
      degrees C. The proteins included a putative S-layer cell surface protein, cell
      surface protein involved with cell adhesion, and trypsin-like serine protease.
      Protease activity was detected in the secreted fraction, and the signal peptide
      cleavage site of the protease was confirmed using Edman sequencing. The
      expression profile of putative cell surface proteins suggests a requirement for
      cell interactions during growth at low temperature. Sequences of the secreted
      proteins were used to compile a dataset containing a further 32 predicted
      secreted proteins from the Methanosarcinaceae. Many of these proteins were also S
      layer cell surface proteins with a variety of predicted roles, particularly in
      cell-cell interaction. Computational analysis of signal peptides revealed a
      preference for lysine in the n-region, leucine in the h-region, and a eucaryal
      type cleavage site, highlighting the mosaic nature of signal peptides in Archaea.
      This is the first study to experimentally characterize secreted proteins from a
      cold-adapted archaeon and provides new insight and a functional dataset for
      studying secretion in Archaea.

PMID- 16944960
TI  - A combined shotgun and multidimensional proteomic analysis of the insoluble
      subproteome of the obligate thermophile, Geobacillus thermoleovorans T80.
AB  - To further our understanding of the biology of the thermophilic bacterium
      Geobacillus thermoleovorans T80, we now report the first proteomic analysis of
      the insoluble subproteome of this isolate. A combination of both shotgun and
      multidimensional methodologies were utilized, and a total of 8628 peptides was
      initially identified by automated MS/MS identification software. Curation of
      these peptides led to a final list of 184 positive protein identifications. The
      proteins from this insoluble subproteome were functionally classified, and
      physiochemical characterization was carried out. Of 15 hypothetical conserved
      proteins identified, we have assigned function to all but four. A total of 31
      proteins were predicted to possess signal peptides. In silico investigation of
      these proteins allowed us to identify four of the five bacterial classes of
      signal peptide, namely, (i) twin-arginine translocation; (ii) Sec-type; (iii)
      lipoprotein, and (iv) ABC transport. In addition, a number of proteins were
      identified that are known to be involved in the transport of compatible solutes,
      known to be important in microbial stress responses.

PMID- 16944961
TI  - Proteomic analysis of human whole and parotid salivas following stimulation by
      different tastes.
AB  - Whole and parotid salivas, collected after stimulation with tastants, were
      analyzed by 2D electrophoresis and mass spectrometry. In whole saliva, the number
      of proteins affected by taste stimulation increased in the order sweet < umami <
      bitter < acid. Annexin A1 and calgranulin A, involved in inflammation, were over
      represented after umami, bitter, and sour stimulations. Their low abundance or
      absence in parotid saliva after bitter stimulation suggested that they originated
      from other oral glands or tissues.

PMID- 16944963
TI  - Pharmacokinetic drug interaction profiles of proton pump inhibitors.
AB  - Proton pump inhibitors are used extensively for the treatment of gastric acid
      related disorders because they produce a greater degree and longer duration of
      gastric acid suppression and, thus, better healing rates, than histamine H(2)
      receptor antagonists. The need for long-term treatment of these disorders raises
      the potential for clinically significant drug interactions in patients receiving
      proton pump inhibitors and other medications. Therefore, it is important to
      understand the mechanisms for drug interactions in this setting. Proton pump
      inhibitors can modify the intragastric release of other drugs from their dosage
      forms by elevating pH (e.g. reducing the antifungal activity of ketoconazole).
      Proton pump inhibitors also influence drug absorption and metabolism by
      interacting with adenosine triphosphate-dependent P-glycoprotein (e.g. inhibiting
      digoxin efflux) or with the cytochrome P450 (CYP) enzyme system (e.g. decreasing
      simvastatin metabolism), thereby affecting both intestinal first-pass metabolism
      and hepatic clearance. Although interactions based on the change of gastric pH
      are a group-specific effect and thus may occur with all proton pump inhibitors,
      individual proton pump inhibitors differ in their propensities to interact with
      other drugs and the extent to which their interaction profiles have been defined.
      The interaction profiles of omeprazole and pantoprazole have been studied most
      extensively. A number of studies have shown that omeprazole carries a
      considerable potential for drug interactions, since it has a high affinity for
      CYP2C19 and a somewhat lower affinity for CYP3A4. In contrast, pantoprazole
      appears to have lower potential for interactions with other medications. Although
      the interaction profiles of esomeprazole, lansoprazole and rabeprazole have been
      less extensively investigated, evidence suggests that lansoprazole and
      rabeprazole seem to have a weaker potential for interactions than omeprazole.
      Although only a few drug interactions involving proton pump inhibitors have been
      shown to be of clinical significance, the potential for drug interactions should
      be taken into account when choosing a therapy for gastric acid-related disorders,
      especially for elderly patients in whom polypharmacy is common, or in those
      receiving a concomitant medication with a narrow therapeutic index.

PMID- 16944964
TI  - Cardiovascular safety profiles of aromatase inhibitors : a comparative review.
AB  - Third-generation aromatase inhibitors (AIs) are now being used for the adjuvant
      treatment of postmenopausal women with breast cancer, and are challenging
      tamoxifen, the previous 'gold standard' of care, in this setting. This review
      evaluates the potential clinical impact of anastrozole, letrozole and exemestane
      on the cardiovascular (CV) system of postmenopausal women with breast cancer.
      Some data for CV safety are available for AIs from the advanced disease setting;
      however, most derive from patients being treated for early disease. CV data on
      anastrozole for the treatment of early breast cancer were taken from the ATAC
      trial, in which anastrozole was compared with tamoxifen in the primary adjuvant
      setting, and the ABCSG trial 8/ARNO 95 combined analysis, in which switching to 3
      years of anastrozole after 2 years of tamoxifen was compared with the standard 5
      years of tamoxifen adjuvant therapy. Letrozole has been studied in the primary
      adjuvant setting and the adjuvant sequencing setting in the BIG 1-98 study, as
      well as in extended adjuvant endocrine therapy after 5 years of tamoxifen in the
      MA-17 trial. For exemestane, results were reviewed from the IES trial, in which
      switching to exemestane following 2-3 years of adjuvant tamoxifen was compared
      with continued tamoxifen treatment. All these trials clearly confirmed that all
      three AIs significantly reduce the risk of thromboembolic events compared with
      tamoxifen. Data on anastrozole versus tamoxifen from the ATAC trial (68 months'
      follow-up) showed a similar incidence of myocardial infarctions (MIs), CV deaths
      and overall deaths for both therapies; however, anastrozole appeared to be
      associated with a lower incidence of cerebrovascular events compared with
      tamoxifen. In addition, the ABCSG trial 8/ARNO 95 study reported no difference in
      terms of MIs for patients switching to anastrozole compared with patients
      continuing tamoxifen treatment. Data from BIG 1-98 (26 months' follow-up)
      suggested that primary adjuvant treatment with letrozole may be associated with a
      significantly greater incidence of CV events and a numerical increase of
      cerebrovascular and cardiac deaths compared with tamoxifen. However, no increase
      in CV events with letrozole was reported from the MA-17 trial. In the IES,
      updated data at 55 months' median follow up showed no significant difference in
      the incidence of MIs and cardiac deaths between patients who switched to
      exemestane compared with those who continued tamoxifen. In conclusion, a
      significantly reduced risk of thromboembolic disease was observed for all three
      AIs compared with tamoxifen. Anastrozole is, at this point, the only AI with a
      detailed benefit-risk profile from over 5 years' follow-up in the adjuvant
      setting. Thus far, no apparent CV-safety concerns have emerged. Preliminary data
      on letrozole and exemestane suggest that longer follow-up is needed for these two
      AIs before being able to fully assess their respective long-term CV toxicity
      profile. The present differences in CV-safety profiles suggest that third
      generation AIs should not be considered as equivalents in clinical practice.

PMID- 16944965
TI  - Errors associated with applying decision support by suggesting default doses for
      aminoglycosides.
AB  - BACKGROUND: Medication errors, and the resultant adverse drug events (ADEs), are
      one of the main preventable causes of morbidity and mortality. Computerised
      physician order entry (CPOE) is reported to reduce the frequency of these errors.
      However, CPOE systems themselves may be associated with errors. The aim of this
      study was to investigate the effects of a CPOE system that displays an initial
      default dose for gentamycin and tobramycin administration on the frequency of
      medication errors and potential ADEs in patients with renal insufficiency.
      METHODS: Gentamycin and tobramycin prescriptions from the CPOE records of a Dutch
      tertiary adult intensive care unit were retrospectively compared with doses
      recommended by a locally developed guideline. The default dose for gentamycin and
      tobramycin in the CPOE system is 240 mg/day. A dose prescribing error was defined
      as an administered dose that exceeded the recommended dose by >10%. RESULTS:
      Three hundred and ninty two prescriptions, relating to 253 patients (of whom 184
      had renal insufficiency), were analysed. There was a high frequency (58%, 227 of
      392) of prescriptions that used the CPOE system's default dose of 240 mg/day. The
      dose was wrong in 73% (165) of these orders. Default orders for patients with
      renal insufficiency amounted to 52% (132 of 259). A total of 86% (113 of 132) of
      these resulted in potential ADEs compared with 53% (66 of 124) for the rest of
      orders (p < 0.0001). DISCUSSION: A markedly high frequency of prescriptions
      followed the default dose value and, in patients with renal insufficiency, there
      was a high frequency of doses exceeding the guideline recommendation (+10%),
      amounting to potential ADEs. CONCLUSION: Initial CPOE dose values for prescribing
      gentamycin and tobramycin, which are based on a fixed default value, form a
      source of potential ADEs for patients with renal insufficiency.

PMID- 16944966
TI  - Long-term safety and tolerability of the lamivudine/abacavir combination as
      components of highly active antiretroviral therapy.
AB  - BACKGROUND: Numerous large, long-term clinical trials have assessed the safety
      and efficacy of the two antiretroviral nucleoside analogs lamivudine and abacavir
      as components of highly active antiretroviral therapy for the treatment of
      patients with HIV-1 infection. This analysis pools the safety data on multi-drug
      regimens containing lamivudine/abacavir in combination with a protease inhibitor,
      non-nucleoside reverse transcriptase inhibitor, or nucleoside reverse
      transcriptase inhibitor. METHODS: Data are presented from 2279 treatment-naive
      HIV-1-infected patients who were enrolled in one of five clinical trials that
      assessed the safety and tolerability of lamivudine/abacavir in combination with a
      third antiretroviral agent. The well characterised combination of
      lamivudine/zidovudine plus efavirenz was used as the comparator arm. All
      available safety data (including data beyond 48 weeks) were used in all analyses,
      which included calculation of treatment emergent laboratory values, adverse
      events (AEs), serious AEs, fatalities, drug discontinuations and any summaries by
      study week of safety data. RESULTS: In the total lamivudine/abacavir group, 1585
      of 2229 (71%) patients experienced at least one drug-related AE during the study
      compared with 247 of 325 (76%) patients in the lamivudine/zidovudine/efavirenz
      treatment group. The most common drug-related AEs reported during the study were
      diarrhoea (19%), nausea (18%) and dizziness (12%) in patients treated with
      lamivudine/abacavir plus a third agent, and nausea (31%), dizziness (27%) and
      headache (16%) in the comparator group. Overall, in the total lamivudine/abacavir
      group there were only three severe (Division of AIDS 1992 toxicity table grade 3
      or 4) AEs that were reported in >1% of subjects: drug hypersensitivity, elevated
      ALT levels and elevated AST levels. In the lamivudine/zidovudine/efavirenz group,
      six severe AEs that occurred in >1% of the safety population were reported. The
      abacavir hypersensitivity reaction rate reported in these five studies was
      comparable with the previously reported rate. In addition, there were no patient
      fatalities attributed by investigators to the study drugs. CONCLUSION: This
      analysis indicates that the combination of lamivudine/abacavir is generally safe
      for the majority of patients when used as part of combination therapy.

PMID- 16944967
TI  - Hepatoblastomas and liver development: a study of cytokeratin immunoexpression in
      twenty-nine hepatoblastomas.
AB  - Hepatoblastomas (HBs) recapitulate liver development. It is possible that HBs
      result from malignant transformation of hepatic precursor cells, and they may
      reflect a blockage in normal development. Here we study the expression of
      cytokeratins (CKs) in order to delineate the immunoprofile and relationship with
      liver development, as well as vimentin and alphafetoprotein (AFP), of HBs.
      Immunohistochemistry was performed in a tissue microarray (TMA) containing
      representative areas of 18 HBs (fetal and/or embryonal and/or mesenchymal); we
      also reviewed 11 cases not included in the TMA. No cases stained for CKs 1, 5/6,
      7, 10, 13, 15, 16, 20, and 34betaE12. CK8 stained 73.07% of fetal, 50% of
      embryonal, and 18% of mesenchymal areas. CK18 stained 100% of epithelial areas.
      CK19 staining was intense and diffuse in 100% of embryonal samples, but it was
      weaker in fetal areas (66.66%). AE1 stained epithelial areas in all cases, and it
      stained 29.41% of mesenchymal areas. AE3 stained 84.61% of embryonal and 60% of
      fetal components. AE1/AE3 showed stronger staining in embryonal (100%) than in
      fetal areas (76.92%). Vimentin staining was strong in embryonal (66.66%) and
      mesenchymal (84.61%) components but weak in fetal areas (8%). Alphafetoprotein
      was positive in only 20% of fetal and 70% of embryonal areas. Our results support
      the hypothesis that immunoexpression of HBs follows the stages of normal liver
      development. Embryonal areas look less differentiated, expressing vimentin and
      biliary epithelium CKs, whereas fetal areas display a more developed phenotype,
      similar to that of mature hepatocytes. These data aid in understanding the
      ontogenesis of HBs and may be used in histopathological diagnosis.

PMID- 16944962
TI  - Therapeutic drug monitoring and pharmacogenetic tests as tools in
      pharmacovigilance.
AB  - Therapeutic drug monitoring (TDM) and pharmacogenetic tests play a major role in
      minimising adverse drug reactions and enhancing optimal therapeutic response. The
      response to medication varies greatly between individuals, according to genetic
      constitution, age, sex, co-morbidities, environmental factors including diet and
      lifestyle (e.g. smoking and alcohol intake), and drug-related factors such as
      pharmacokinetic or pharmacodynamic drug-drug interactions. Most adverse drug
      reactions are type A reactions, i.e. plasma-level dependent, and represent one of
      the major causes of hospitalisation, in some cases leading to death. However,
      they may be avoidable to some extent if pharmacokinetic and pharmacogenetic
      factors are taken into consideration. This article provides a review of the
      literature and describes how to apply and interpret TDM and certain
      pharmacogenetic tests and is illustrated by case reports. An algorithm on the use
      of TDM and pharmacogenetic tests to help characterise adverse drug reactions is
      also presented. Although, in the scientific community, differences in drug
      response are increasingly recognised, there is an urgent need to translate this
      knowledge into clinical recommendations. Databases on drug-drug interactions and
      the impact of pharmacogenetic polymorphisms and adverse drug reaction information
      systems will be helpful to guide clinicians in individualised treatment choices.

PMID- 16944968
TI  - Correlation of minimal residual disease by assessing Wilms tumor gene expression
      and engraftment by variable number of tandem repeats in children with leukemia
      posthematopoietic stem cell transplantation.
AB  - An important measure to ensure successful follow-up in patients with allogeneic
      stem cell transplant is to evaluate for engraftment. Recent studies have shown
      that detecting minimal residual disease is important in order to predict early
      clinical relapse. We followed 88 leukemic patients with pre- and posttransplant
      Wilms tumor gene (WT1) levels to predict relapse and variable number of tandem
      repeats (VNTR) for engraftment. We have found that high pretransplant WT1 levels
      correlated significantly with relapse in all patient groups, but more
      significantly in the acute nonlymphoblastic leukemia (ANLL) patients.
      Posttransplant WT1 level correlated with VNTR status such that low WT1 is
      associated invariably with VNTR of 100% donor origin, while high WT1 is
      associated with VNTR of 20%. The association is significant in all patients,
      specifically in ANLL patients. In this preliminary study, we demonstrate that
      patients harboring detectable levels of WT1 prior to stem cell transplant have a
      higher chance of relapse, and posttransplant WT1 and VNTR status appeared to be
      dependent parameters predicting relapse when present in the posttransplant
      period. By combining 2 highly sensitive molecular techniques, we have found that
      this combined technique provided us with a promising alternative for overcoming
      the limitations imposed by each separate procedure. More studies are necessary
      before we can come to any significant conclusions.

PMID- 16944969
TI  - Fulminant neonatal liver failure in siblings: probable congenital hemophagocytic
      lymphohistiocytosis.
AB  - Familial hemophagocytic lymphohistiocytosis (HLH) is an autosomal recessive
      disorder of immune regulation characterized by fever, splenomegaly, cytopenia,
      hypertriglyceridemia, hypofibrinogenemia, and hyperferritinemia. Although
      presentation usually occurs during the first 2 years of life, congenital
      presentation is rare. We report siblings with a presumptive diagnosis of familial
      HLH who presented with hydrops fetalis and severe hepatic involvement ultimately
      resulting in their deaths. This report emphasizes the difficulty of confirming
      the diagnosis of HLH. However, establishing the diagnosis has important
      implications for genetic counseling and family planning. HLH should be considered
      in the setting of perinatal liver failure. The immunologic basis of the disease
      is incompletely understood but testing for natural killer cell function, and
      perforin defects may be helpful in establishing a diagnosis. HLH can be treated
      with chemotherapy, immunotherapy, and stem cell transplantation.

PMID- 16944970
TI  - Alveolar Capillary Dysplasia in a Patient with Down's Syndrome.

PMID- 16944971
TI  - Amnion degeneration over fetal placental surface vessels possibly resulting from
      focal hypoxia: a case report.
AB  - The monoamnionic placenta of this twin gestation had focal amnion necrosis, but
      this was present only over the fetal surface vessels of one twin; this twin also
      developed cerebral atrophy. We hypothesize that this degeneration is due to a
      more severely reduced oxygen tension in its vessels. The placental amnion
      epithelium may undergo several degenerative processes, including amnion nodosum
      and changes due to meconium staining. Sonography had disclosed what appeared to
      be a dividing membrane, but this was not found at birth when monoamnionic twins
      with entangled cords presented. The amnion degeneration was present only over the
      large surface fetal vessels of the placenta of that twin who also developed
      central nervous system degeneration, and macrophage infiltration was confined to
      the same lesions. Focal hypoxia from entangling cords may have caused this
      defect.

PMID- 16944972
TI  - Peripheral primitive neuroectodermal tumor with postchemotherapy neuroblastoma
      like differentiation.
AB  - We report the case of an 11-year-old girl with a retroperitoneal tumor in the
      left upper quadrant. The girl was admitted to hospital with weight loss and a
      painless abdominal mass that on biopsy was diagnosed as a peripheral primitive
      neuroectodermal tumor/Ewing sarcoma (pPNET/EWS) of the soft tissue. The patient
      underwent chemotherapy followed by surgical resection of the tumor 5 months after
      diagnosis. The posttreatment residual viable tumor showed a morphologic
      appearance resembling a neuroblastoma. Interphase and metaphase fluorescent in
      situ hybridization (FISH) studies performed on the pretreatment and posttreatment
      samples showed the presence of a t(11;22) rearrangement resulting in EWSR1/FLI1
      gene fusion consistent with pPNET/EWS in both specimens. This case is unusual in
      the sense of showing the typical gene fusion for pPNET/EWS both in the pretherapy
      sample with the typical morphological appearance of this tumor and in the
      posttherapy specimen showing neural differentiation suggestive of a
      neuroblastoma.

PMID- 16944973
TI  - Co-occurrence of massive perivillous fibrin deposition and chronic
      intervillositis: case report.
AB  - Chronic intervillositis (CI) and massive perivillous fibrin deposition (MFD),
      together with its related entity, maternal floor infarction (MFI), are rare and
      poorly understood placental lesions. Both MFD/MFI and CI are associated with poor
      fetal outcome and high risk of recurrence. We report a patient who was found to
      have both MFD and CI in the same placenta, resulting in severe intrauterine fetal
      growth restriction and intrauterine fetal death at 37 weeks of gestation.
      Characteristic histological findings included both very extensive perivillous
      deposition of fibrinoid material and a heavy infiltrate of CD68-positive
      macrophages/monocytes in the maternal intervillous space. To our knowledge, this
      is the first time the co-occurrence of MFD and CI is reported in the literature.

PMID- 16944975
TI  - Cytogenetic and p53 profiles in congenital cystic adenomatoid malformation:
      insights into its relationship with pleuropulmonary blastoma.
AB  - Congenital cystic adenomatoid malformation (CCAM), a developmental anomaly of
      lung, shares many features with the pediatric tumor pleuropulmonary blastoma
      (PPB). Both may show benign epithelium-lined cysts and mesenchymal proliferation,
      often with skeletal muscle differentiation. Before its recognition as a distinct
      entity, PPB was described in several reports as "rhabdomyosarcoma arising in
      CCAM." Abnormal karyotypes in PPB often show excess material from chromosome 8.
      It has also been suggested that PPB may harbor p53 mutations. We examined the
      karyotype and searched for p53 mutations (via immunostaining and single-strand
      conformation polymorphism analysis) in 11 CCAM and in 2 PPB. Karyotypes were
      normal in all CCAM and showed clonal abnormalities in both PPB. There was marked
      and diffuse immunopositivity for nuclear p53 in the epithelial cells of CCAM and
      PPB. Strong staining was also observed in approximately 50% of the stromal cells
      in all PPB, but was seen in the stroma of only 2 of 10 CCAM, where it was faint
      and focal. TP53 mutations were not identified in CCAM or PPB. We conclude that
      CCAM does not contain the clonal chromosomal aberrations reported in PPB and
      shows less stromal p53 immunostaining than PPB. Since p53 mutations were not
      identified in either entity, the observed p53 immunoreactivity may be caused by
      another mechanism; its role in PPB and CCAM pathogenesis remains to be
      determined. Overall, these findings provide evidence that CCAM is nonneoplastic.
      Although some may view CCAM as a PPB precursor, it remains biologically distinct
      in terms of karyotype and p53 status.

PMID- 16944976
TI  - A protocol for the handling of tissue obtained by operative lung biopsy:
      recommendations of the chILD pathology co-operative group.
AB  - This is the first of a series on pediatric pulmonary disease that will appear as
      Perspectives in Pediatric Pathology over the coming months. The series will
      include practical issues, such as this protocol for handling lung biopsies and
      another on bronchoalveolar lavage in childhood, as well as reviews of advances in
      various areas in pediatric pulmonary pathology. It has been 11 years since the
      last Perspectives on pulmonary disease. Much has happened since then in this
      area, and this collection will highlight some emerging and rapidly advancing
      areas in pediatric lung disease. These will include a review of molecular
      mechanisms of lung development, and another of mechanisms of pulmonary vascular
      development. The surfactant system and its disorders, as well as recent advances
      in the biology of the pulmonary neuroendocrine system and mechanisms of
      respiratory viral disease, will be addressed. Articles on pulmonary hypertension,
      pulmonary neoplasia, and pediatric lung transplantation, with their implications
      for the pediatric pathologist, are also planned. The contributors to this series
      are a diverse group with special interests and expertise in these areas. As Dr.
      William Thurlbeck noted in his foreword to the previous volume, Pulmonary
      Disease, volume 18 of Perspectives in Pediatric Pathology, pediatric pathology
      had been largely concerned with phenomenology, rather than with mechanisms, model
      systems, and experimental investigation. I think he would have been pleased to
      see the changes that have occurred over the past 10 years in pediatric lung
      biology and pathology in particular, because these were particularly favored
      interests of his later years.

PMID- 16944977
TI  - High TGFbeta1, estrogen receptor, and aromatase gene expression in a large cell
      calcifying sertoli cell tumor (LCCSCT): implications for the mechanism of
      oncogenesis.
AB  - Large cell calcifying Sertoli cell tumors (LCCSCT) are associated with Carney
      complex and Peutz-Jeghers syndrome. The mechanisms linking these 2 genetic
      defects to the genesis of this tumor are obscure. Studies of CYP19 (aromatase)
      and transforming growth factor (TGF)-beta1 messenger RNA (mRNA) abundance,
      estrogen receptor (ER), TGFbeta1, and TGFbeta type II receptor (R)
      immunochemistry were carried out in the testis of a patient with this tumor to
      gain information on possible mechanisms of cell tumor development. Testicular
      tissue of a prepubertal patient, collected at gonadectomy, was separated into 2
      macroscopically distinct fractions: tumoral nodules (Tu) and extratumoral, normal
      looking testicular tissue (ExTu). The patient was a 9.5-year-old boy with a 5
      year history of bilateral gynecomastia (Tanner stage 4), no pubic hair, incipient
      genital development, and bilateral testicular nodules. Multiple pigmented lesions
      of the skin were present. Bilateral mammectomy and gonadectomy was performed. RNA
      was extracted from Tu and ExTu for semiquantitative reverse transcriptase
      polymerase chain reaction of CYP19 and TGFbeta1. Protein expression of ER,
      TGFbeta1, and TGFbeta type II R in Tu and ExTu was detected by
      immunohistochemistry. Cell proliferation was estimated by Ki-67 antigen
      immunochemistry and apoptosis using a modified TUNEL assay. Mean expression of
      aromatase and TGFbeta1 mRNAs in Tu was 6- and 2.3-fold higher than in ExTu,
      respectively (P<0.05). Tumoral cells exhibited ER staining with a predominant
      extranuclear localization. Positive staining of Sertoli cells in Tu was higher
      than in ExTu. TGFbeta1 immunostaining of the interstitial cells in Tu was higher
      than in ExTu. TGFbeta type II R immunostaining was detected in most Sertoli and
      interstitial cells, but intensity in ExTu was lower than in Tu. No significant
      difference was detected in the proliferation index, but in Tu, the percentage of
      Sertoli cells in apoptosis (1.4%) was significantly lower (P<0.01) than in ExTu
      (14.0%). The following hypothesis is proposed. The congenital gene defects of
      Carney complex or of Peutz-Jeghers syndrome might trigger a cascade of
      intracellular events that leads to overexpression of aromatase in Sertoli cells,
      favoring the development of a LCCSCT. At some point in the evolution of the
      disease, a mutational event might induce a higher expression of the ER. Also,
      TGFbeta1 protein expression is increased in neighboring cells. In this
      environment, TGFbeta1 might switch from tumor suppressor to oncogenic factor and,
      along with estrogen-ER complexes, might favor tumor progression by inhibiting
      apoptosis.

PMID- 16944978
TI  - Sirenomelia of an intracytoplasmic sperm injection conceptus: a case report and
      review of mechanism.
AB  - Postmortem dissection of the 18-week male conceptus, product of intracytoplasmic
      sperm injection (ICSI), demonstrated the hallmark findings of sirenomelia. The
      lower legs were fused and the left knee was rotated medially. Internal organs
      showed hypoplastic lungs, a multicystic kidney, and unilateral ureteral
      hypoplasia. The vitelline artery was absorbed, in a classic fashion, into the
      umbilical artery and communicated with the aorta at a point proximal to the iliac
      arteries. The tributaries distal to this point were hypoplastic. This finding is
      consistent with previously documented cases of sirenomelia and is thought to be
      the pathogenetic mechanism resulting in a vascular steal from the lower
      extremities. A rare finding was the presence of a penis on the dorsal side just
      below a perforate anus. In this case report, we discuss the pertinent clinical
      history and autopsy findings. A brief review of the mechanism thought to give
      rise to sirenomelia is provided. To our knowledge, this is the first reported
      case of sirenomelia in an ICSI conceptus.

PMID- 16944979
TI  - Quantity and distribution of eosinophils in the gastrointestinal tract of
      children.
AB  - There are a lack of data on the quantity and location of eosinophils in the
      gastrointestinal tract of healthy individuals. Accordingly, we examined
      gastrointestinal biopsies obtained during endoscopic evaluation of pediatric
      patients. Biopsies were previously interpreted as having no diagnostic
      abnormality. The presence of extracellular eosinophil constituents and the
      quantity of eosinophils in atopic versus nonatopic individuals was determined. In
      the esophagus, eosinophils were present in only 2.7% of high-power fields (hpf),
      with a mean value of 0.03+/-0.10 eosinophils/hpf (mean+/-standard deviation) and
      a maximum of 1 eosinophil/hpf. Examination of the antrum and fundus revealed
      similar numbers of eosinophils in the lamina propria (1.9+/-1.3 and 2.1+/-2.4
      eosinophils/hpf, respectively), with no eosinophils observed in the surface
      epithelium. In the small intestine, there were 9.6+/-5.3 (maximum, 26
      eosinophils/hpf) and 12.4+/-5.4 eosinophils/hpf (maximum, 28 eosinophils/hpf) in
      the intercryptal lamina propria of the duodenum and ileum, respectively. The
      number of eosinophils in the surface epithelium and crypt epithelium was minimal.
      In the large intestine, the highest concentration of eosinophils was observed in
      the cecum (20.3+/-8.2 eosinophils/hpf; maximum, 50 eosinophils/hpf), and there
      were lower concentrations in the transverse and sigmoid colon (16.3+/-5.6 and
      8.3+/-5.9 eosinophils/hpf, respectively). The percentage of fields demonstrating
      extracellular eosinophil granules in all gastrointestinal segments was 70% to
      93%, and extracellular granules were most numerous at the edge of the biopsy
      (P<0.05). Atopic and nonatopic patients had comparable numbers of eosinophils.
      These data establish baseline gastrointestinal eosinophil values in pediatric
      patients without apparent pathological disease.

PMID- 16944980
TI  - KAI-1 expression in pediatric high-grade osteosarcoma.
AB  - Recent evidence implicates cell surface proteins of the tetraspanin superfamily
      in the process of metastasis whereas the downregulation of KAI-1, a member of the
      tetraspanin family, is associated with an aggressive clinical phenotype in
      several types of human cancers. To determine if expression of KAI-1-1 is
      associated with any known prognostic marker or clinical outcome in high-grade
      osteosarcoma, we examined 91 nondecalcified archival samples from 47 patients for
      the expression of KAI-1. Archival, paraffin-embedded, and decalcified pathologic
      samples were examined by immunohistochemistry and results were correlated to
      clinical outcomes and known prognostic markers. There were 46 samples from
      diagnostic biopsies (1 diagnostic sample was not available), 32 tumor resection
      samples, and 13 metastasis samples. Thirty-three percent (n=30) of the samples
      expressed KAI-1 (16 biopsies, 9 resections, and 5 metastasis). KAI-1 expression
      was not significantly related to known prognostic markers or to either tumor
      necrosis after neoadjuvant therapy or the incidence of metastasis at diagnosis.
      KAI-1 expression was not significantly different between paired diagnostic tumor
      samples and either resection or metastasis tumor samples. Twenty-five patients
      remain alive at a median follow-up of 95 months. The overall and progression-free
      survival percentages at 5 years were 62% and 47% for KAI-1-positive patients and
      49% and 38% for KAI-1-negative patients, respectively. This difference was not
      statistically significant. We conclude that KAI-1 is expressed in a proportion of
      high-grade osteosarcoma but is not of clinical significance and cannot be used to
      stratify treatment groups for these patients.

PMID- 16944981
TI  - Pathologic and molecular analysis in a family with rare mixed supravalvar aortic
      and pulmonic stenosis.
AB  - Nonsyndromic supravalvar aortic stenosis (SVAS) is an obstructive vascular
      disorder often inherited in an autosomal dominant manner. With pulmonary artery
      involvement, stenotic lesions are nearly always peripheral or downstream of the
      pulmonic valve. In rare cases when the supravalvar pulmonic region is affected,
      the stenoses usually improve over time and rarely affect prognosis. We evaluated
      a unique family in which 10 of 14 individuals have nonsyndromic SVAS and 7 of the
      10 affected family members with SVAS have the rare finding of supravalvar
      pulmonic stenosis (SVPS). In at least 2 of these individuals, the severity of
      SVPS was so significant that it led to death in early infancy. Pathologic
      examination of stenotic lesions in this kindred group revealed concentrically
      organized smooth muscle cells separated by dense elastic fibers. In contrast, the
      arterial pathology reported for other individuals with nonsyndromic SVAS
      demonstrates increased numbers of hypertrophied smooth muscle cells separated by
      thin, fragmented elastin fibers. Molecular analysis identified a novel ELN
      mutation within the donor splice site of exon 16, which may be responsible for
      the unique phenotype and distinct elastin histopathology found in this kindred.

PMID- 16944982
TI  - Unusual fallopian tube neoplasm in a 10-year-old patient with Proteus syndrome: a
      case report and review of the literature.
AB  - We report a case of fallopian tube and peritoneal lesions resected from a 10-year
      old girl with Proteus syndrome. The papillary fallopian tube tumor expressed CA
      125 and demonstrated negative staining for CEA, CD15, calretinin, and CK 5/6.
      Nondilated portions of fallopian tube exhibited evidence of an in situ component.
      This patient was also found to have peritoneal mesothelial hyperplasia as well as
      cystic peritoneal lesions of mesothelial origin, with positive calretinin
      staining. This case provides direct evidence of both Mullerian and mesothelial
      lesions arising concurrently in a patient with Proteus syndrome and represents
      the 1st documented fallopian tube neoplasm. Previously reported lesions involving
      the female and male genital tracts in patients with Proteus syndrome are
      reviewed.

PMID- 16944983
TI  - Squamous cell carcinoma arising in a pediatric intra- and paravertebral teratoma.
AB  - A 7-year-old boy presented with a 1-year history of back pain radiating to his
      left scapula and arm, with tenderness to palpation over the area. Laboratory
      studies were unremarkable. Computed tomographic scan showed a mixed lytic and
      sclerotic process at the T5-T6 level of the vertebral column in continuity with
      an adjacent paravertebral soft tissue mass. Nuclear medicine scan demonstrated
      increased uptake in the T5 vertebral body. Histology revealed invasive squamous
      cell carcinoma infiltrating mature, gliotic neural tissue, with areas of necrosis
      and prominent perivascular space involvement. Associated vertebral fragments
      showed bone destruction, reactive bone formation, and fibrosis. By
      immunohistochemistry, the carcinoma cells were positive for cytokeratin AE1/AE3,
      cytokeratin 5/6, EMA, and MIC-2 (membranous staining). The mature neural tissue
      was positive for GFAP; immature neural elements were not identified. Based on
      morphologic, immunohistochemical, and clinical features, this lesion was
      diagnosed as invasive squamous cell carcinoma arising within an intravertebral
      and paravertebral teratoma.

PMID- 16944984
TI  - Adenovirus infection within stromal cells in a pediatric small bowel allograft.
AB  - Adenovirus infection is not uncommon in pediatric small bowel transplant
      recipients. Histopathologic findings include characteristic epithelial changes of
      intranuclear inclusions and smudging of nuclei. We present a case of adenovirus
      within stromal cells of the lamina propria in a biopsy from a small bowel
      allograft. Immunohistochemistry and double-labeled immunofluorescence were
      performed using antibodies against adenovirus, CD31, vimentin, cytokeratin, and
      CD163 on the allograft intestinal biopsy. Electron microscopy was done to confirm
      the presence of viral particles and to attempt to confirm the origin of the
      infected cells. The index biopsy showed scant cells within the lamina propria
      double-labeled with vimentin and adenovirus. Several cells showed predominantly
      cytoplasmic staining for adenoviral antigen. Intranuclear adenoviral particles
      were found in several cells of the lamina propria by electron microscopy. A
      subsequent biopsy showed typical adenoviral intranuclear inclusions within
      surface enterocytes. Adenovirus may infect stromal cells within the lamina
      propria. Although the typical location of adenoviral inclusions in small bowel is
      the surface epithelial cell nuclei, some cases may show inclusions within stromal
      cells. This observation may be important in the pathobiology of adenoviral
      infection, especially in the setting of pediatric transplantation. This finding
      should alert pathologists examining small bowel transplant biopsies, particularly
      those biopsies with extensive ulceration, to include careful surveillance of the
      lamina propria.

PMID- 16944985
TI  - Anal and ano-urogenital malformations: a histopathological study of "imperforate
      anus" with a reconstruction of the pathogenesis.
AB  - Histopathological information about "anorectal malformations" is scarce and the
      pathogenesis still controversial. Autopsy specimens of 20 human fetuses and
      newborns with "main" types of the disorder were studied histologically.
      Supplemented with surgical-anatomical data from the literature and with
      information from our own and earlier embryological research in animal models as
      well as from recent observations on the normal development of the human perineum,
      the study allowed for a new reconstruction of the pathogenesis of the disorder.
      The histological analysis of the malformations in human fetuses and newborns
      showed a ventralward deviation of the anal canal as the principal deformity. Ano
      urogenital communications and differently structured ectopic anocutaneous canals
      issued from anywhere between the bladder and the vestibular/urethral orifice
      (female urethra excluded) and between the orifice and the usual site of the anus,
      respectively, or they ended blindly, but with a suggestion of lost communication.
      They occurred isolated or in association with other primary or secondary regional
      anomalies. Patho-embryological data from animal models revealed that the
      deviation was caused by defective development of the dorsal cloaca and not by
      disturbances in a series of fusion processes inside and outside the cloaca, as is
      currently believed. This mechanism fits well into recent adjustments of ideas
      about the normal development of the perineum. The cause of the defect is still
      obscure, but a malfunctioning of cells ingressing from an end-stage primitive
      streak that affects the dorsal side of the prospective cloaca appears most
      likely. The data collected permit a new reconstruction of the pathogenesis of
      anal and ano-urogenital malformations.

PMID- 16944986
TI  - Cardiac Registry screening for DiGeorge Critical Region deletion using loss of
      heterozygosity analysis.
AB  - DiGeorge (DGS), velocardiofacial, and conotruncal anomaly face syndromes comprise
      a phenotypic spectrum that is associated with a submicroscopic 22q11.2 deletion
      in the majority of cases. These syndromes variably express complex congenital
      heart disease, cellular immune deficits, hypocalcemia, craniofacial anomalies,
      and learning disabilities. This retrospective study correlates the presence of a
      deletion in this region with autopsy and clinical findings in a cohort of
      patients selected from the Cardiac Registry at Boston Children's Hospital. DNA
      was extracted from formalin-fixed paraffin-embedded cardiac tissue sampled from
      189 patients with conotruncal anomalies. Polymerase chain reaction (PCR) was
      performed using 4 fluorescently labeled oligonucleotide primer pairs for unique
      short tandem repeat polymorphisms in the DGS critical region. The PCR products
      were analyzed for loss of heterozygosity (LOH), and a deletion was assumed when
      at least 3 consecutive loci demonstrated homozygosity. Of the 189 cases, 16 (8%)
      met our criteria for LOH and were assumed to have a deletion. These patients
      included 6 (35%) of 17 patients diagnosed clinically with DGS prior to death. Of
      the 10 non-DGS patients with LOH, 4 had aortic atresia and 3 had tetralogy of
      Fallot, both frequently seen in DGS. Polymerase chain reaction is a useful
      screening alternative to fluorescence in situ hydridization for detecting 22q11.2
      deletions in archived tissue samples. This study identified a probable deletion
      in a subset of cases from a cardiac registry with cardiac defects associated with
      the DGS phenotype.

PMID- 16944988
TI  - The pathogenesis of villitis of unknown etiology: analysis with a new conjoint
      immunohistochemistry-in situ hybridization procedure to identify specific
      maternal and fetal cells.
AB  - The conjoint immunohistochemistry-in situ hybridization (IHC-ISH) procedure
      permits, under routine light microscopic conditions, simultaneous documentation
      of either a male or female karyotype plus the immunological phenotype of
      individual cells within paraffin-embedded tissues. We have used this technique to
      characterize the inflammatory response in placental villitis of unknown etiology
      (VUE). A male placenta with severe VUE and appropriate control placentas were
      analyzed. In situ hybridization probes concurrently label both the X and Y
      chromosomes. On the same tissue section, individual cells were characterized with
      antibodies to CD3, CD68, or CD20. The amnion and syncytiotrophoblast were
      delineated by cytokeratin antibody (AE1/AE3). A complete karyotyping was
      performed on amnion cells to validate the procedure. Amnion cell karyotyping
      confirmed the accuracy of the procedure. The VUE case revealed that 88.8% of
      intravillous CD3+ lymphocytes were female (maternal), while 11.2% were male
      (fetal). Intervillous CD3+ lymphocytes and CD68+ macrophages were universally
      female. Intravillous CD68+ cells were only 10.5% female. Perivillous CD68+ cells
      were 94.6% female. Remarkably, multinucleated giant cells were exclusively
      maternal. This study confirms that lymphocytes in VUE are predominately but not
      exclusively maternal T cells. Our findings indicate that invasion of fetal villi
      by maternal T cells is associated with focal destruction of the
      syncytiotrophoblast, clarifying how placental immuno-defensive mechanisms may be
      contravened.

PMID- 16944989
TI  - Tetralogy of Fallot, hypertrophic cardiomyopathy, and Down's syndrome: a rare and
      challenging combination.
AB  - A case of the combination of tetralogy of Fallot, hypertrophic cardiomyopathy,
      and Down's syndrome is reported here and is the first report on the combination
      of the 3 entities. Tetralogy of Fallot is often associated with chromosomal
      aberration, while hypertrophic cardiomyopathy associates with certain gene loci.
      Our experience with treating this patient, although ultimately unsuccessful, may
      provide useful information in any future cases.

PMID- 16944991
TI  - Early diagnosis of colorectal cancer. Diagnostic delay reduction or rather
      screening programs?

PMID- 16944990
TI  - Ectopic pancreas associated with choledochal cyst and multiseptate gallbladder.
AB  - Congenital choledochal cyst is a rarely seen malformation of childhood,
      particularly when associated with multiseptate gallbladder or ectopic pancreas.
      The current case represents a 15-day-old boy with jaundice. Ultrasonography
      suggested a cystic lesion, probably of the common bile duct. The patient
      underwent a total excision of type I choledochal cyst and gallbladder with Roux
      en-Y anastomosis, and a wedge biopsy from the liver. Gross examination revealed
      multiple septa dividing the gallbladder into multiple compartments. The outer and
      inner surfaces of the choledochal cyst were unremarkable. Microscopically, the
      cyst wall was composed of dense fibrous tissue with a single layer of cubic to
      columnar cells constituting the overlying epithelium. Serial sections
      incidentally revealed ectopic pancreatic tissue lying along the cyst wall
      characterized by acini, islets, and ductal structures with endocrine cells
      reactive for chromogranin A. Septa dividing the gallbladder were composed of
      fibrotic stalks containing smooth muscle fibers. Areas of papillary hyperplasia
      and intestinal metaplasia of gallbladder epithelium were also noted. The liver
      biopsy specimen demonstrated the presence of intrahepatic bile ducts,
      subsequently confirmed by cytokeratin 7. To our knowledge, this case represents
      the 1st one associated with these 3 entities and only the 2nd choledochal cyst
      with ectopic pancreatic tissue in its wall.

PMID- 16944992
TI  - The colorectal carcinoma prognosis factors. Significance of diagnosis delay.
AB  - INTRODUCTION: detection of early-stage colorectal carcinoma (CRC)--( Dukes A or
      B)--provides better survival rates in these patients. Thus, the effectiveness of
      screening programs in asymptomatic patients or of early diagnosis in symptomatic
      individuals has been postulated. The aim of this study was to establish whether a
      delay in diagnosis or other factors are related to CRC stage. PATIENTS AND
      METHODS: a retrospective study was performed on 96 patients with CRC. Age at
      diagnosis, gender distribution, intestinal disorders, diagnosis delay, primary
      sign and -regarding CRC- localization, stage (Dukes) and grade of differentiation
      (well differentiated; non-well differentiated; poorly differentiated) were
      recorded. RESULTS: diagnosis delay was 185 +/- 190 days. Patients delay in
      obtaining a diagnosis was 119 +/- 158 days. In 40% of patients CRC was diagnosed
      at an early stage (Dukes A or B), and in 13% CRC was poorly differentiated. The
      only factor with an independent effect on Dukes stage was tumor differentiation
      (p: 0.0012). Distal location was associated with less advanced tumors without
      statistical significance (p: 0.156). CONCLUSION: based on the presented data, a
      greater effort regarding screening programs for healthy people seems warranted,
      as improved survival has been demonstrated when diagnosis delay is reduced,
      particularly in patients with the highest mean delay.

PMID- 16944993
TI  - Risk factors associated with Helicobacter pylori infection. A population-based
      study conducted in the province of Ourense.
AB  - OBJECTIVES: to identify the relationship between Helicobacter pylori infection
      and various factors that have been described in other studies in the general
      adult population in the province of Ourense. MATERIAL AND METHODS: three hundred
      and eighty-three participants were enrolled in a study on the prevalence of
      Helicobacter pylori infection. All participants filled in a questionnaire under
      supervision, and the data obtained were examined by means of a univariate
      analysis. The odds ratio corresponding to each variable studied was calculated
      with their corresponding 95% confidence intervals. Furthermore, a multivariate
      analysis was performed. RESULTS: the univariate analysis revealed an association
      between infection and: age, place of residence during childhood, current social
      status based on the head of the family s profession, current blue collar/white
      collar profession of the head of the family, sharing a bedroom during childhood,
      type of drinking water, and contact with animals during childhood. No association
      was found with respect to the presence of dyspeptic symptoms. The multivariate
      analysis disclosed that only age is an independent risk factor associated with
      infection. CONCLUSION: age has been identified as the only independent risk
      factor associated with Helicobacter pylori infection in this population-based
      study. The univariate analysis has detected other factors. No association has
      been identified with respect to dyspeptic symptoms.

PMID- 16944994
TI  - Esophagoenteral stents in patients with recurrent gastric adenocarcinoma.
AB  - One of the problems that can appear in patients with total gastrectomy for
      adenocarcinoma with esophagoenteral anastomosis is the appearance of a stenosis
      of the anastomosis. These stenosis are frequently malignant due to relapse of
      neoplasia. The therapeutic possibilities available are the surgical bypass or
      palliative treatment. There is very little experience described in the literature
      (21 cases) on the placing of self-expandable metal stents as a palliative
      treatment for the symptoms of stenosis.We present our experience of 3 patients,
      in whom 4 esophageal stents were fitted (1 covered and 3 uncovered) with good
      results. The dysphagia disappeared or improved, it allowed the ingestion of a
      soft diet and meant an improvement in the quality of life and at the same time
      stopped the weight loss. It seems an effective palliative treatment as a
      treatment for dysphagia in patients with tumoral relapse in the anastomosis of
      total gastrectomies.

PMID- 16944995
TI  - Surgical treatment of esophageal leiomyoma: an analysis of our experience.
AB  - INTRODUCTION: leiomyoma is the most common benign esophageal neoplasm. Surgical
      treatment (enucleation) has traditionally been the therapy of choice. The advent
      of minimally invasive techniques has produced an increase in endoscopic
      approaches to the detriment of open surgery. OBJECTIVE: the aim of this study was
      to compare the results obtained with open surgery and with laparoscopic surgery
      in this kind of pathology. MATERIAL AND METHODS: we performed a retrospective
      study of all leiomyomas operated for in our center between 1986 and 2004, and
      obtained 9 cases of esophageal leiomyoma. Four were women and five men, between
      the ages of 40 and 70, with a mean age of 53.5 years. The most frequent symptoms
      were heartburn (5 cases), dysphagia (3 cases), and retrosternal pain (3 cases).
      Surgery was in all the cases an enucleation. An open approach was performed in 5
      cases (3 thoracotomies and 2 laparotomies), and an endoscopic approach in 4 (2
      thoracoscopies and 2 laparoscopies). RESULTS: the mean postoperative hospital
      stay was 5.12 days (range 2-8 days). This was shorter for endoscopic approaches
      versus open surgery (3.25 vs. 7 days). There was no case of esophageal mucosal
      perforation or reconversion. No death, intraoperative complication, or tumor
      relapse was described. Only 2 patients had complications: post-surgical thoracic
      pain, and intestinal obstruction by adhesions 8 years after surgery. CONCLUSION:
      enucleation is an easier procedure and constitutes the therapy of choice for
      esophageal leiomyoma. This approach has to be laparoscopic. We think that muscle
      borders should be closed after enucleation, and that biopsy is not indicated
      preoperatively.

PMID- 16944996
TI  - "Downhill" varices. A rare cause of esophageal hemorrhage.
AB  - "Downhill" varices or upper esophageal varices are a rare cause of proximal
      digestive tract hemorrhage with only 16 cases described in the literature. In our
      series, hemorrhage due to "downhill" varices represents 0.1% of all acute
      esophageal variceal bleeding. Their etiology differs from that of the usual
      "uphill" varices secondary to portal hypertension, and the clinical management
      should be directed to vascular obstruction if present. We report a case of an 89
      year-old male with hemorrhagic "downhill" varices not associated, as usually,
      with superior vena cava obstruction or compression, but with severe pulmonary
      hypertension and drug-related hemorrhagic risk factors, whose removal proved
      sufficient to prevent rebleeding.

PMID- 16944997
TI  - Budesonide for ulcerative colitis.
AB  - In this review, we examined studies published on oral and topical formulations of
      budesonide (Entocort and Budenofalk, in Spain: Entocord and Intestifalk) for the
      treatment of ulcerative colitis. This glycocorticosteroid has a potent local
      action and an important first-pass liver metabolism. It has proven successful
      over the last years as a controlled-release formulation. It obtained results
      similar to prednisolone, without the latter s significant suppression of plasma
      cortisol. Many publications exist on the effects of oral budesonide for the
      treatment of Crohn s disease (CD). These have led to the registration of this
      drug for the treatment of CD. Studies on oral formulations of budesonide for the
      treatment of ulcerative colitis (UC) are scarce. After reviewing published
      evidence, we suggest the conduction of controlled trials for the treatment of UC
      to obtain evidence-based efficacy and safety results in order to benefit patients
      with this form of inflammatory bowel disease (IBD).

PMID- 16944998
TI  - Factors involved in the pathogenesis of Helicobacter pylori infection.

PMID- 16944999
TI  - Lower GI bleeding secondary to a stromal rectal tumor (rectal GIST).

PMID- 16945000
TI  - [Intestinal linitis plastica, late metastases in signet-ring gastric
      adenocarcinoma].

PMID- 16945001
TI  - [Giant colonic hernia with incarcetarion of transverse colon].

PMID- 16945002
TI  - [Psoas abscess complicating Crohn's disease: review of 5 cases].

PMID- 16945003
TI  - [Ambulatory laparoscopic cholecystectomy].

PMID- 16945004
TI  - REACH testing requirements must not be driven by reproductive toxicity testing.

PMID- 16945005
TI  - In vitro tests within the REACH information strategies.
AB  - Tonnage-based information requirements are specified in the proposal on the
      regulation on the Registration, Evaluation and Authorisation of Chemicals (REACH)
      in the European Union. The hazard assessment for toxic endpoints should be
      performed by using a tiered approach, i.e. as an information strategy (IS),
      starting with an evaluation of all of the data already available, including
      animal in vivo and in vitro data, and human evidence and case reports, as well as
      data from (Quantitative)-Structure Activity Relationships ([Q]SARs) or read
      across, before any further testing is suggested. To contribute to the
      implementation of the REACH system, the Nordic countries launched two projects:
      1) a review of currently used testing strategies, including a comparison with the
      REACH requirements; and 2) the development of detailed ISs for skin and eye
      irritation/corrosion. The review showed that the ISs and classification criteria
      for the selected endpoints are inconsistent in many cases. In the classification
      criteria, human data and in vivo test results are usually the prerequisites.
      Other types of information, such as data from in vitro studies, can sometimes be
      used, but usually as supportive evidence only. This differs from the REACH ISs,
      where QSARs, read-across and in vitro testing are important elements. In the
      other part of the project, an IS for skin and eye irritation/corrosion was
      proposed. The strategy was "tested" by using four high production volume (HPV)
      chemicals: hydrogen peroxide, methyl tertiary-butyl ether (MTBE), trivalent
      chromium, and diantimony trioxide, but only MTBE and trivalent chromium are dealt
      with in this paper. The "test" revealed that in vivo data, human case reports and
      physical-chemical data were available and could be used in the evaluation.
      Classification could be based on the proposed IS and the existing data in all
      cases, except for the eye irritation/corrosion of trivalent chromium. Weight-of
      evidence analysis appeared to be a useful step in the ISs proposed, and including
      it in the REACH strategies should be considered. For these chemicals, few in
      vitro and (Q)SAR data were available--more of these data would be generated, if
      the relevant guidance and legislation on classification were updated.

PMID- 16945006
TI  - Human tissue for in vitro research as an alternative to animal experiments: a
      charitable "honest broker" model to fulfil ethical and legal regulations and to
      protect research participants.
AB  - Research with human tissue offers the possibility not only of improving
      preclinical pharmaceutical research and safety assessment, but also of the
      substitution of some animal experiments. Surgically removed human tissue is
      discarded after pathological evaluation. This tissue would be of enormous value
      for research, especially in the pharmaceutical branch, if it were readily
      available in an ethically and legally approved manner. But there are public
      concerns about the use of human tissue, especially for "commercial" purposes,
      such as in the pharmaceutical industry. The question is whether the ethical
      boundaries are sufficiently respected in the course of striving for industrial
      profit. To overcome this problem, a clear procedure for tissue donation,
      collection, supply and allocation must be established, which is guaranteed to be
      independent of special interests. The persisting problem seems to be the lack of
      an authority which asks for informed consent, coordinates tissue as well as
      blinded data collection, and supplies research facilities with tissue samples in
      a transparent manner. Therefore, a charitable, state-controlled foundation acting
      as an "honest broker" was initiated, to cover the ethical and legal aspects, as
      well as to protect the research participants in their use of human tissue as an
      alternative to animal experiments.

PMID- 16945007
TI  - Assessment of the skin irritation potential of chemicals by using the SkinEthic
      reconstructed human epidermal model and the common skin irritation protocol
      evaluated in the ECVAM skin irritation validation study.
AB  - Currently, two reconstructed human skin models, EpiDerm and EPISKIN are being
      evaluated in an ECVAM skin irritation validation study. A common skin irritation
      protocol has been developed, differing only in minor technical details for the
      two models. A small-scale study, applying this common skin irritation protocol to
      the SkinEthic reconstructed human epidermis (RHE), was performed at ZEBET at the
      BfR, Berlin, Germany, to consider whether this protocol could be successfully
      transferred to another epidermal model. Twenty substances from Phase III of the
      ECVAM prevalidation study on skin irritation were tested with the SkinEthic RHE.
      After minor, model-specific adaptations for the SkinEthic RHE, almost identical
      results to those obtained with the EpiDerm and EPISKIN models were achieved. The
      overall accuracy of the method was more than 80%, indicating a reliable
      prediction of the skin irritation potential of the tested chemicals when compared
      to in vivo rabbit data. As a next step, inter laboratory reproducibility was
      assessed in a study conducted between ZEBET and the Department of Experimental
      Toxicology, Schering AG, Berlin, Germany. Six coded substances were tested in
      both laboratories, with three different batches of the SkinEthic model. The assay
      results showed good reproducibility and correct predictions of the skin
      irritation potential for all six test chemicals. The results obtained with the
      SkinEthic RHE and the common protocol were reproducible in both phases, and the
      overall outcome is very similar to that of earlier studies with the EPISKIN and
      EpiDerm models. Therefore, the SkinEthic skin irritation assay test protocol can
      now be evaluated in a formal "catch-up" validation study.

PMID- 16945008
TI  - Integrated testing strategies for use in the EU REACH system.
AB  - Integrated testing strategies have been proposed to facilitate the process of
      chemicals risk assessment to fulfil the requirements of the proposed EU REACH
      system. Here, we present individual, decision-tree style, strategies for the
      eleven major toxicity endpoints of the REACH system, including human health
      effects and ecotoxicity. These strategies make maximum use of non-animal
      approaches to hazard identification, before resorting to traditional animal test
      methods. Each scheme: a) comprises a mixture of validated and non-validated
      assays (distinguished in the schemes); and b) decision points at key stages to
      allow the cessation of further testing, should it be possible to use the
      available information to classify and label and/or undertake risk assessment. The
      rationale and scientific justification for each of the schemes, with respect to
      the validation status of the tests involved and their individual advantages and
      limitations, will be discussed in detail in a series of future publications.

PMID- 16945009
TI  - The relevance of genetically altered mouse models of human disease.
AB  - The impetus to develop useful models of human disease and toxicity has resulted
      in a number of large-scale mouse mutagenesis programmes. This, in turn, has
      stimulated considerable concern regarding the scientific validity and welfare of
      genetically altered mice, and the large numbers of mice that are required by such
      programmes. In this paper, the scientific advantages and limitations of
      genetically altered mice as models of several human diseases are discussed. We
      conclude that, while the use of some such mouse models has contributed
      considerably to an understanding of human disease and toxicity, other genetically
      altered mouse models have limited scientific relevance, and fewer have positively
      contributed to the development of novel human medicines. Suggestions for
      improving this unsatisfactory situation are made.

PMID- 16945010
TI  - An interview with Michel Bouvier, Ph.D. Interview by Vicki Glaser.

PMID- 16945012
TI  - High throughput screening identified a substituted imidazole as a novel RANK
      pathway-selective osteoclastogenesis inhibitor.
AB  - Receptor activator of nuclear factor-kappaB (NF-kappaB) (RANK) plays a key role
      in the differentiation, activation, and survival of osteoclasts. Upon activation
      of RANK with RANK ligand (RANKL), osteoclast precursor cells differentiate into
      tartrate-resistant acid phosphatase (TRAP)-positive, multinucleated osteoclasts.
      To identify compounds that block osteoclastogenesis, a cell-based assay was
      developed using RAW264.7 cells stably transfected with a TRAP promoter-dependent
      reporter gene as a surrogate readout for differentiation. Described herein is the
      strategy for high throughput screening and subsequent secondary biological assays
      for hit triage, which resulted in the identification of compound 1, a 4
      nitroimidazole derivative, that specifically inhibited RANKL-induced TRAP gene
      and protein expression. Compound 1 did not affect the tumor necrosis factor-alpha
      or lipopolysaccharide-induced TRAP-luciferase response, suggesting selective
      inhibition of the RANKL-induced pathway. Reverse transcription polymerase chain
      reaction analysis confirmed the inhibition of expression of osteoclast marker
      genes, such as TRAP, cathepsin K, and carbonic anhydrase type II. Compound 1 did
      not inhibit the RANKL-induced activation of a NF-kappaB reporter gene, or p38
      kinase activity, suggesting a mechanism of action downstream of NF-kappaB.
      Together, these results suggest that we have identified a RANK pathway-specific
      inhibitor able to block the RANKL-induced osteoclast differentiation process. The
      hit identification strategy described here can be applied to other cell-based
      assays using an indirect surrogate readout to improve success rates.

PMID- 16945013
TI  - High-content screening analysis of the p38 pathway: profiling of structurally
      related p38alpha kinase inhibitors using cell-based assays.
AB  - The complexity of the p38 mitogen-activated protein kinase (MAPK) signaling
      pathway presents challenges to understanding the efficacy of p38 inhibitors.
      Biochemical recombinant kinase assays and tumor necrosis factor alpha (TNFalpha)
      secretion assays are typically used to evaluate p38alpha inhibitors, but they do
      not provide insight into proximal intracellular events. Stimulation of the
      pathway evokes a cascade of phosphorylation events, accompanied by movement of
      molecules to different cellular compartments. Herein, we describe the profiling
      and potency comparison of a large set of p38alpha inhibitors with a pyrimidinone,
      imidazopyrimidine, or triazolopyrimidine core against biochemical recombinant
      p38alpha kinase activity, lipopolysaccharide (LPS)-mediated TNFalpha secretion by
      THP-1 cells, and a set of cellular imaging assays in SW1353 chondrocytes and baby
      hamster kidney cells. These pathway assays included p38 phosphorylation, MAPK
      activated protein kinase 2 translocation, and heat shock protein (HSP) 27
      phosphorylation. We established that HSP27 phosphorylation correlates well with
      LPS-induced TNFalpha secretion, validating our cellular imaging assays. We also
      found that the choice of cells and inducer can profoundly affect cellular potency
      results. High-content analysis may reveal signaling details, enriching our
      understanding of the mechanism of action of p38alpha inhibitors.

PMID- 16945014
TI  - Enzyme fragment complementation binding assay for p38alpha mitogen-activated
      protein kinase to study the binding kinetics of enzyme inhibitors.
AB  - The majority of protein kinase assays used in drug discovery research are enzyme
      activity assays. These assays are based on the measurement of phosphorylated
      protein or peptide substrate, which is the end product of the enzyme reaction.
      Since most kinase inhibitors are ATP competitive, prediction of the activity of
      compounds in cellular systems based on potency values in enzyme activity assays
      is complex, as this should take into account the affinity of the enzyme for ATP
      and the cellular ATP concentration. The fact that some of the most successful
      kinase inhibitors, such as STI 571 (imatinib mesylate, Gleevec, Novartis
      Pharmaceuticals, East Hanover, NJ), act through binding to the inactive isoform
      of the kinase provides another limitation of enzyme activity assays. Binding
      assays allow separate measurement of compound affinity to active and inactive
      kinase and do not require ATP or substrate in the reaction. Recently, a non
      radioactive kinase binding assay for p38 mitogen-activated protein kinase has
      become available from DiscoveRx (Fremont, CA). The assay method, called
      HitHunter, utilizes enzyme fragment complementation of Escherichia coli beta
      galactosidase to generate an assay signal by chemiluminescence. We have
      reconfigured the commercial assay kit to study the binding kinetics of two known
      reference inhibitors of the alpha-isoform of p38, the pyridinyl imidazole SB
      203580 and the diaryl urea BIRB 796. Our data confirm the slow association
      kinetics of BIRB 796 as compared to SB 203580, which corresponded with the
      requirement of a relatively long preincubation time to obtain maximal effect in a
      cellular assay. Although neither of the two compounds showed preference for
      either active or inactive p38alpha, our data demonstrate that the HitHunter
      kinase binding assay can be used to select compounds that specifically target
      inactive kinase.

PMID- 16945015
TI  - Quantitative characterization of mitosis-blocked tetraploid cells using high
      content analysis.
AB  - A range of cellular evidence supporting a G1 tetraploidy checkpoint was obtained
      from different assay methods including flow cytometry, immunoblotting, and
      microscopy. Cancer research would benefit if these cellular properties could
      instead be measured by a single, quantitative, automated assay method, such as
      high content analysis (HCA). Thus, nocodazole-treated cells were fluorescently
      labeled for different cell cycle-associated properties, including DNA content,
      retinoblastoma (Rb) and histone H3 phosphorylation, p53 and p21(WAF1) expression,
      nuclear and cell sizes, and cell morphology, and automatically imaged, analyzed,
      and correlated using HCA. HCA verified that nocodazole-induced mitosis block
      resulted in tetraploid cells. Rb and histone H3 were maximally
      hyperphosphorylated by 24 h of nocodazole treatment, accompanied by cell and
      nuclear size decreases and cellular rounding. Cells remained tetraploid and
      mononucleated with longer treatments, but other targets reverted to G1 levels,
      including Rb and histone H3 dephosphorylation accompanied by cellular
      respreading. This was accompanied by increased p53 and p21(WAF1) expression
      levels. The range of effects accompanying nocodazole-induced block of mitosis and
      the resulting tetraploid cells' reversal to a pseudo-G1 state can be
      quantitatively measured by HCA in an automated manner, recommending this assay
      method for the large-scale biology challenges of modern cancer drug discovery.

PMID- 16945016
TI  - Rb+ efflux through functional activation of cardiac KCNQ1/minK channels by the
      benzodiazepine R-L3 (L-364,373).
AB  - The slow delayed rectifier K+ current, Iks, encoded by KCNQ1 (KvLQT1)/KCNE1
      (mink) genes, contributes to cardiac action potential repolarization and
      determines the heartbeat rate. Mutations in either KCNQ1 or KCNE1 that reduce Iks
      cause long-QT syndrome (LQTS), a disorder of ventricular repolarization that
      results in cardiac arrhythmia and sudden death. A well-recognized potential
      treatment for LQTS caused by reduction of Iks is to enhance functional activation
      of cardiac KCNQ1/KCNE1 channels. In the present study, we generated a stable
      Chinese hamster ovary cell line that expresses KCNQ1/KCNE1 channels confirmed by
      electrophysiology. Using a pharmacological tool compound R-L3 (L-364,373 [(3-R)
      1,3-dihydro-5-(2-fluorophenyl)-3-(1H-indol- 3-ylmethyl)-1-methyl-2H-1,4
      benzodiazepin-2-one]), which activates KCNQ1/mink channels, we then developed and
      validated a non-radioactive rubidium (Rb+) efflux assay that directly measures
      the functional activity of KCNQ1/KCNE1 channels by atomic absorption
      spectroscopy. Our results show that the validated Rb+ efflux assay can be used
      for screening of KCNQ1/KCNE1 openers that potentially treat LQTS in both
      inherited and acquired forms. In addition, the assay also can be used for
      evaluation of possible long-QT liability during cardiac selectivity of new
      chemical entities.

PMID- 16945017
TI  - A cellular assay for measuring the inhibition of glycogen synthase kinase-3 via
      the accumulation of beta-catenin in Chinese hamster ovary clone K1 cells.
AB  - Glycogen synthase kinase-3 (GSK3) is a serine-threonine protein kinase that
      exists as two isozymes, GSK3alpha and GSK3beta. It plays important roles in
      regulating cell structure, function, and survival, and dysregulation of its
      function is linked to disorders such as Alzheimer's disease and type II diabetes.
      In resting cells, GSK3 is active and regulates the function of many downstream
      targets, including beta-catenin. We describe the development of a cell-based
      assay designed to measure the activity of GSK3 by directly measuring the
      accumulation of beta-catenin in Chinese hamster ovary clone K1 (CHOK1) cells.
      Beta-catenin levels were assessed using an antibody-based staining protocol with
      a luminometric readout. The assay is set up in a 96-well format. The use of GSK3
      inhibitors demonstrated that this assay could be used to compare the effects of
      various small molecules on GSK3 inhibition in CHOK1 cells.

PMID- 16945019
TI  - Cell-based assay strategy for identification of motif-specific RANK signaling
      pathway inhibitors.
AB  - Osteoclasts, the principal bone-resorbing cells, not only play a pivotal role in
      skeletal development and maintenance but are also implicated in the pathogenesis
      of various bone disorders such as postmenopausal osteoporosis, bone erosion in
      inflammatory conditions, and tumor-induced osteolysis. As a result, several
      antiresorptive drugs (agents capable of inhibiting osteoclast formation and/or
      function) have been developed and are widely used to prevent and treat these bone
      diseases. However, current antiresorptive agents either lack satisfactory
      efficacy or cause serious side effects in clinical management of these bone
      disorders. Almost a decade ago, the receptor activator of nuclear factor-kappaB
      (RANK) ligand (RANKL) was identified as an essential factor required for
      osteoclast formation. RANKL exerts the effect by binding to its receptor RANK on
      osteoclast precursors. RANKL also has a decoy receptor, osteoprotegerin (OPG),
      which inhibits RANKL function by competing with RANK for RANKL. The unraveling of
      the critical role for the RANKL/RANK/OPG system in osteoclast biology provides an
      unprecedented opportunity to develop more effective antiresorptive drugs.
      Unfortunately, the agents currently under development, such as OPG, RANK-Fc, and
      anti-RANKL antibodies, all inherit a serious drawback--lack of specificity, due
      to the involvement of the RANKL/RANK/OPG system in other biological processes
      such as immune response and mammary gland development. Thus, future efforts may
      need to shift to explore RANK signaling pathways as more effective therapeutic
      targets. Here, we review our current understanding of RANK signaling in
      osteoclasts and then discuss the potential of RANK signaling pathways as
      therapeutic pathways. Moreover, we further describe a strategy for constructing
      novel cell-based systems for identifying compounds inhibiting signaling from two
      recently identified RANK motifs through high throughput screening. We hope that
      this review will not only provide readers with an update on progress in this area
      of research but, more importantly, will also serve as a starting point for
      further discussion and eventual development of new strategies for harnessing the
      ultimate potential of the RANKL/RANK/OPG system as antiresorptive therapeutic
      targets.

PMID- 16945018
TI  - Real-time and high throughput monitoring of cAMP in live cells using a
      fluorescent membrane potential-sensitive dye.
AB  - Adenosine-3',5'-cyclic monophosphate (cAMP) conveys the signals from G-protein
      coupled receptors (GPCRs) and regulates a variety of downstream cellular events.
      However, there are few robust assays available for measuring cAMP in live cells.
      Most of the existing cAMP assays require cell lysis and/or have relatively low
      throughput. We report a live cell-based cAMP assay that has been developed to
      record the real-time changes in intracellular cAMP. By employing a mutated cyclic
      nucleotide-gated ion channel (CNGC) as the cAMP biosensor, the change of cAMP
      level is coupled to the change of transmembrane potential that is measured
      through a new fluorescent membrane potential (MP)-sensitive dye, HLB 021-152. We
      have successfully used HLB 021-152 for homogeneously monitoring cAMP stimulations
      in live cells under both serum-containing and serum-free environments. Upon
      stimulating the endogenous or heterogenous GPCRs on CNGC-cloned human embryonic
      kidney 293 cells with agonists, the fluorescence signal of HLB 021-152 increases
      rapidly. It has much greater assay dynamic range than DiSBAC2(3), the existing
      "gold standard" dye for measuring cellular MP. This new MP dye can be readily
      formulated for high throughput screening of GPCR modulators either with serum or
      without serum.

PMID- 16945020
TI  - Exploring the molecular basis of tumor metastasis by microarray analysis.
AB  - Over the past decade, microarray technology has become a powerful tool to provide
      a genome-wide view of genetic or epigenetic changes associated with tumor
      metastasis. To extract biologically meaningful information from the vast amounts
      of microarray data, it is crucial to choose suitable biological systems and have
      vigilant experimental design. In this review, I will discuss several experimental
      systems that are used to identify genes involved in tumor metastasis by
      microarray analysis. Also highlighted are the pros and cons for each system. In
      particular, I will describe our experience of using microarray technology to
      identify the transcription factor Twist as an essential player in tumor
      metastasis.

PMID- 16945022
TI  - Systematic review of the association between respiratory diseases and oral
      health.
AB  - BACKGROUND: The purpose of this review was to investigate evidence for a possible
      etiological association between oral health and pneumonia or other respiratory
      diseases. METHODS: The following data sources were used: Ovid MEDLINE (In-Process
      & Other Non-Indexed Citations, Daily Update, and OLDMEDLINE); Cumulative Index to
      Nursing & Allied Health Literature; Evidence Based Medicine of Cochrane Central
      Register of Controlled Trials; Cochrane Database of Systematic Reviews; Database
      of Abstracts of Reviews of Effects; EMBASE; Health and Psychosocial Instruments;
      HealthSTAR; International Pharmaceutical Abstracts; PubMed; and Google Scholar
      from the earliest record until July 2005. Studies were selected from randomized
      controlled clinical trials and longitudinal, cohort, case-control, and
      epidemiological studies. Searches were limited to English language and human
      studies. RESULTS: A total of 728 articles were searched for relevancy, determined
      by article title, abstract, and full copy, resulting in a yield of 19 studies
      that met our inclusion criteria. These articles were read and scored
      independently by the reviewers to obtain the evidence for this review: 1) the
      potential risk factors for pneumonia were identified as the presence of
      cariogenic and periodontal pathogens, dental decay, and poor oral hygiene in five
      studies; 2) a weak association between periodontal disease and chronic
      obstructive pulmonary disease (COPD) was identified in four poor to fair studies;
      and 3) 10 studies were retained providing evidence that interventions aiming to
      improve oral health reduced the progression or occurrence of pneumonia.
      CONCLUSIONS: 1) There is fair evidence (II-2, grade B recommendation) of an
      association of pneumonia with oral health (odds ratio [OR]=1.2 to 9.6 depending
      on oral health indicators). 2) There is poor evidence of a weak association
      (OR<2.0) between COPD and oral health (II-2/3, grade C recommendation). 3) There
      is good evidence (I, grade A recommendation) that improved oral hygiene and
      frequent professional oral health care reduces the progression or occurrence of
      respiratory diseases among high-risk elderly adults living in nursing homes and
      especially those in intensive care units (ICUs) (number needed to treat [NNT]=2
      to 16; relative risk reduction [RRR]=34% to 83%).

PMID- 16945023
TI  - Periodontal status in smokers and never-smokers: clinical findings and real-time
      polymerase chain reaction quantification of putative periodontal pathogens.
AB  - BACKGROUND: Smoking is a well-known risk factor for destructive periodontal
      disease, but its relationship with periodontal status and subgingival microbiota
      remains unclear. Inherent limitations of microbiological methods previously used
      may partly explain these mixed results, and real-time polymerase chain reaction
      (PCR) has been presented as a valid alternative. The aim of the present study was
      to investigate the clinical condition and microbiological profile of patients
      with chronic periodontitis as related to the habit of smoking. METHODS: Fifty
      patients (33 to 59 years old), 25 smokers and 25 never-smokers, constituted the
      sample. The visible plaque index (VPI), gingival bleeding index (GBI), bleeding
      on probing (BOP), periodontal probing depth (PD), clinical attachment loss (CAL),
      and gingival crevicular fluid (GCF) volume were recorded. Real-time PCR
      quantified Porphyromonas gingivalis, Micromonas micros, Dialister pneumosintes,
      Actinobacillus actinomycetemcomitans and total bacteria in subgingival samples.
      RESULTS: Smokers and never-smokers showed similar values for VPI, GBI, and BOP.
      Smokers had deeper PD in buccal/lingual sites and higher CAL independently of the
      tooth surface. The GCF volume was smaller in smokers, independent of the PD.
      Similar amounts of total bacteria and P. gingivalis were observed for both
      groups. Significantly higher numbers of D. pneumosintes and M. micros were
      present in smokers and associated with moderate and deep pockets. When heavy
      smokers were considered, higher counts of total bacteria, M. micros, and D.
      pneumosintes were observed. CONCLUSIONS: Smoking seems to have a detrimental
      impact on the periodontal status and microbiological profile of patients with
      periodontitis. Compared to never-smokers, smokers had deeper pockets, greater
      periodontal destruction, and higher counts of some putative periodontal
      pathogens.

PMID- 16945024
TI  - Impaired masticatory behavior in subjects with reduced periodontal tissue
      support.
AB  - BACKGROUND: Mechanoreceptors situated in the periodontal ligament provide
      detailed information about intensive and spatial aspects of tooth loads, which
      support the neural control of masticatory forces. We asked whether a reduced
      periodontal ligament due to periodontitis, and, thus, an altered mechanoreceptive
      innervation of the teeth, would affect masticatory behavior when subjects used
      incisors to hold and split food. METHODS: We tested 11 subjects with reduced
      periodontal tissue support that rendered 30% to 70% alveolar bone loss for at
      least one pair of opposing anterior incisors. Forces were recorded when subjects
      used their affected incisors to hold half of a peanut for approximately 4 seconds
      and then split it. Age- and gender-matched healthy subjects served as the control
      group. None of the participants showed acute oral symptoms or massive periodontal
      inflammation. RESULTS: The test group used greater force when holding food
      between the teeth (1.1+/-0.4 N [ mean+/-1 SD]) compared to the control group
      (0.4+/-0.2 N). Hold forces used by subjects in the test group were also more
      variable, both within and between trials. The increase in bite force applied to
      split the peanut was slower and more hesitant for subjects in the test group
      compared to the control group. CONCLUSIONS: Reduced periodontal tissue support
      accompanies impaired regulation of masticatory forces. Faulty mechanoreceptive
      innervation of the periodontal ligament explains the elevated hold force, whereas
      a change in biting strategy due to the weakened support of the teeth may account
      for the more defensive food-splitting behavior.

PMID- 16945025
TI  - Matrix metalloproteinase-1 gene polymorphism in renal transplant patients with
      and without gingival enlargement.
AB  - BACKGROUND: Gingival enlargement frequently occurs in transplant patients
      receiving immunosuppressive drugs. It was hypothesized that gingival enlargement
      associated with cyclosporin use results in a disturbance of the homeostatic
      balance, which is characterized by an increase in the number of fibroblasts and
      volume of the extracellular matrix. Matrix metalloproteinase (MMP) serves as an
      initiator of extracellular matrix destruction. The aim of this study was to
      determine whether there is an association between genotypes of the MMP-1 gene and
      gingival enlargement in kidney transplant patients. METHODS: Sixty-one unrelated
      kidney transplant patients with gingival enlargement and 121 control transplant
      patients without enlargement were enrolled in the study. Six months after
      transplantation, all patients were given medication, which included cyclosporin
      A, and gingival enlargement was assessed. MMP-1 polymorphism was determined using
      the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      assay. RESULTS: In kidney transplant patients with gingival enlargement, the mean
      score of gingival enlargement was 1.42+/-0.63, whereas in control subjects, it
      was 0.0. There were no significant differences in the frequency of -1607 1G>2G
      alleles and genotypes between patients with and without gingival enlargement. In
      all subjects (N=182) and in patients without gingival enlargement, the genotype
      distribution met Hardy-Weinberg equilibrium criteria, whereas in patients with
      gingival enlargement, it was markedly different (P<0.06). There was a trend for
      carriers of at least the 1G allele to have an increased risk of gingival
      enlargement, but the trend was not statistically significant (odds ratio, 2.32;
      P<0.073). CONCLUSION: No association between the MMP-1 gene polymorphism and
      gingival enlargement was revealed in kidney transplant patients who were
      administered cyclosporin A as a principal immunosuppressive agent.

PMID- 16945026
TI  - Interleukin-10 haplotype frequencies in children with gingivitis.
AB  - BACKGROUND: Polymorphisms in the promoter region of the interleukin (IL)-10 gene
      have been identified at positions -1082 (G-->A), -819 (C-->T), and -592 (C-->A).
      Linkage disequilibrium between alleles -819*C, and -592*C was observed. A
      previous study addressed the association between the -1082*A allele and
      gingivitis in white Caucasian children. The aim of this case-control study was to
      test whether differences could exist between children with and without gingivitis
      in the distribution of IL-10 alleles and haplotypes at positions -1082, -819, and
      -592. METHODS: A total of 248 subjects aged 8 to 12 years from the University
      Dental Hospital of Manchester were enrolled in this study. According to gingival
      and bleeding on probing indices, 84 children were classified as controls and 164
      as children with gingivitis. Amplification refractory mutation system-polymerase
      chain reaction (ARMS-PCR) was used for genotyping IL-10 polymorphisms. Allele and
      haplotype frequencies were calculated by direct counting and by a haplotype
      frequency estimation (EH) program. Differences between subjects with gingivitis
      and controls in the frequency of haplotypes were determined by a chi2 test of
      homogeneity. RESULTS: The GCC/GCC genotype, which has been associated with
      increased production of IL-10, was significantly more frequent in controls than
      in children with gingivitis (36% versus 23%) (P=0.036). In addition, there was a
      marginally significant difference between controls and cases in the frequency of
      haplotypes (P=0.06). The GCC haplotype was more frequent in controls than in
      children with gingivitis (60% versus 50%). In contrast, the ACC and ATA
      haplotypes were more frequent in children with gingivitis (27% and 23% versus 19%
      and 21% in controls). CONCLUSION: These findings suggest that IL-10 gene promoter
      polymorphisms could have an active role in the pathogenesis of gingivitis in
      Caucasian children.

PMID- 16945027
TI  - Association of matrix metalloproteinase-9 promoter gene polymorphism with chronic
      periodontitis.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) are related to tissue destruction
      and remodeling events in periodontal diseases. A single nucleotide polymorphism
      in the promoter region of human MMP-9 gene is associated with the risk of some
      inflammatory diseases. Therefore, the aim of this study was to investigate the
      association between MMP-9 promoter polymorphism and severe generalized chronic
      periodontitis in a Turkish population. METHODS: Samples of venous blood and DNA
      were obtained from 70 severe generalized chronic periodontitis patients and 70
      healthy subjects. The alleles of the C/T polymorphism at position -1562 in the
      promoter region of the MMP-9 gene were distinguished by cutting with the SphI
      restriction enzyme. Genotype and allele frequencies were calculated, and data
      were analyzed by the chi2 test. RESULTS: There was a significant difference in
      MMP-9 genotypes between chronic periodontitis patients and healthy controls. The
      odds ratios for the CT genotype and the combination of CT and TT genotypes were
      0.4 (95% confidence interval, 0.17 to 0.93; P=0.02) and 0.37 (95% confidence
      interval, 016 to 0.85; P=0.01) relative to the subjects with the CC genotype,
      respectively. CONCLUSION: MMP-9 promoter gene polymorphism seems to be associated
      with severe generalized chronic periodontitis.

PMID- 16945028
TI  - Assessment of single nucleotide polymorphism at IL-1A+4845 and IL-1B+3954 as
      genetic susceptibility test for chronic periodontitis in Maharashtrian ethnicity.
AB  - BACKGROUND: The inflammatory response that is directed in large part by
      proinflammatory cytokine interleukin (IL)-1 is genetically determined, with some
      people having a more vigorous response than others to the same stimulus. The
      reason for this is speculated that the dysregulated production of IL-1 in some
      individuals overrides the feedback mechanisms that normally master the dose of
      inflammation to a level sufficient to fight microbial invasion without long
      lasting damage to the tissues involved. The aims of the present study were to
      determine the distribution of IL-1 gene polymorphism (IL-1A+4845 and IL-1B+3954)
      and their association with periodontal disease severity and to determine the
      significance of detecting the composite genotype (IL-1A allele2+IL-1B allele2)
      versus detecting either of them alone. METHODS: A total of 120 subjects were
      included and divided into four groups of 30 subjects each, namely, healthy, mild,
      moderate, and severe periodontitis groups. After a complete clinical examination,
      DNA was isolated from 0.5 ml blood. Specific primers were used to detect the
      presence of IL-1 gene polymorphism with the help of polymerase chain reaction
      (PCR) and subsequent allele detection with restriction fragment length
      polymorphism (RFLP) and separation by gel electrophoresis. RESULTS: The
      distribution of the allele1 homozygous genotype was 3% in the severe
      periodontitis group, and the distribution for the allele2 genotype was 30%. A
      higly significant difference (Wilcoxon signed-rank test; P<0.001) was seen
      between subjects positive and negative for the composite genotype. CONCLUSIONS:
      Results of the present study reinforced the association of the IL-1 genotype as a
      risk factor for severe chronic periodontitis. Positivity for the composite
      genotype was found to be significantly associated with severe chronic
      periodontitis (odds ratio [OR]=12.42).

PMID- 16945029
TI  - Additional effect of dentifrices on the instant efficacy of toothbrushing.
AB  - BACKGROUND: Inconclusive evidence exists in the literature with regard to the
      additional effect of the use of dentifrice on plaque removal. The present study
      was undertaken to test whether the use of dentifrice during toothbrushing
      contributes to the instant cleaning efficacy of the brushing procedure. METHODS:
      Three groups of patients, 40 subjects each, were randomly assigned to one of
      three dentifrices that differed with respect to the relative dentin abrasivity
      (RDA) value. After a 48-hour plaque accumulation, subjects brushed under
      supervision in a split-mouth order with or without the use of dentifrice (total
      time=2 minutes). RESULTS: Plaque reductions varied between 51% and 58% for the
      three dentifrices. The overall analysis showed a mean difference of 3% in plaque
      reduction in favor of brushing without dentifrice (P=0.017). The type of
      dentifrice did not influence this observed difference (P=0.506). Also, the order
      of the brushing procedure (starting the brushing procedure with or without
      dentifrice) had no interaction with the effect of dentifrice on the brushing
      (P=0.187). CONCLUSIONS: The use of dentifrice does not contribute to the instant
      mechanical plaque removal during manual toothbrushing. A higher dentifrice
      abrasivity does not seem to contribute to increased plaque removal with a manual
      toothbrush. It appears that the mechanical action provided by the use of a
      toothbrush is the main factor in the plaque-removing process.

PMID- 16945030
TI  - Long-term success of implants replacing a single molar.
AB  - BACKGROUND: The aim of this study was to assess the long-term success and
      survival rates of implants replacing a single molar between two natural teeth and
      to evaluate the influence of implant characteristics on implant success. METHODS:
      The study was based on a consecutive cohort of 81 patients who received implants
      to replace a single molar between the years 1994 and 2004. Inclusion criteria for
      patients were having an implant replacing a molar between two natural teeth and
      follow-up data of at least 6 months. Data were recorded regarding the incidence
      of complications and success and survival rates of these implants. RESULTS: The
      range of follow-up was from 6 to 125 months (mean: 36 months). Smoking was
      reported by 18.5% of patients. The replacement of a mandibular molar was more
      frequent (87.7%), with 25.9% of the implants placed immediately after tooth
      extraction. Two implants were used to replace a single molar in seven patients
      (8.6%). The failure rate was 7.4% (six implants failed: three had broken necks,
      and three failed because of infection or bone loss). Complications included
      suppuration in 11.1% of implants and a pocket around the implant in two patients
      (2.5%). No relation was found among failure, complications, timing of implant
      placement, and smoking habits. CONCLUSION: A single implant can serve as a good
      long-term and predictable treatment modality to replace a single molar with low
      complication and failure rates.

PMID- 16945031
TI  - Relationship between salivary melatonin and severity of periodontal disease.
AB  - BACKGROUND: Melatonin possesses antioxidant, free-radical scavenging, and
      immunoenhancing properties that promote fibroblast activity and bone
      regeneration. The aim of this study was to examine the possible links between
      salivary melatonin levels and the severity of periodontal disease using the
      community periodontal index (CPI). METHODS: Thirty-seven patients with different
      degrees of periodontal disease were studied. Salivary and plasma melatonin levels
      (by radioimmunoassay), salivary/plasma melatonin ratio, and CPI status were
      collected for each patient. The Spearman correlation coefficient was used to
      analyze relationships among variables. RESULTS: Data showed a significant
      correlation between CPI and salivary/plasma melatonin ratios. When saliva volume
      was controlled for, a significant correlation (P<0.05) was found between lower
      salivary melatonin and a worse CPI. This finding suggests that melatonin may act
      as a protector against free radicals produced by inflammatory periodontal
      diseases. CONCLUSIONS: Salivary melatonin levels varied according to the degree
      of periodontal disease. As the degree of periodontal disease increased, the
      salivary melatonin level decreased, indicating that melatonin may act to protect
      the body from external bacterial insults. Therefore, melatonin may be potentially
      valuable in the treatment of periodontal diseases, although further research is
      required to validate this hypothesis.

PMID- 16945032
TI  - Microbiota of the dorsum of the tongue after plaque accumulation: an experimental
      study in humans.
AB  - BACKGROUND: The purpose of the present investigation was to determine the effect
      of the absence of tongue hygiene on the microbiota of the dorsum of the tongue.
      METHODS: Ten volunteers (aged 19 to 22 years) entered the study at baseline and
      were instructed to abstain from tongue cleaning for 7 days, followed by a period
      of 3 days without any kind of oral hygiene. Subsequently, a period of 21 days of
      washout was employed, and this protocol was repeated three times. Microbiological
      samples were obtained from the dorsum of the tongue at baseline and at the end of
      the period of coating accumulation and analyzed using the checkerboard DNA-DNA
      hybridization technique. RESULTS: The species found in highest mean counts at
      baseline and day 10 were Prevotella melaninogenica and Veillonella parvula. The
      mean bacterial total counts enhanced significantly during the study (from
      17.1x10(6) to 33.7x10(6)). Proportions of red and blue complexes and levels of 18
      species also increased after the period of coating accumulation, including
      several periodontal pathogens, such as Prevotella intermedia, Prevotella
      nigrescens, Streptococcus constellatus, Tannerella forsythensis, Porphyromonas
      gingivalis, Treponema denticola, and P. melaninogenica. CONCLUSION: The tongue
      surface could be an important reservoir for periodontal pathogens and may play a
      role in the recolonization of tooth surfaces and in the etiology of oral
      halitosis.

PMID- 16945033
TI  - Periodontal disease and coronary heart disease.
AB  - BACKGROUND: Several epidemiological studies have demonstrated an association
      between periodontal disease and coronary heart disease (CHD). The association
      could be a result of confounding by mutual risk factors. The present study was
      undertaken in a Danish population to reveal the significance of common risk
      factors. METHODS: The investigation was conducted as a case-control study
      comprising 250 individuals: 110 individuals with verified CHD from a Department
      of Cardiovascular Medicine and 140 control individuals without CHD from the
      Copenhagen City Heart Study. Information on diabetic status, smoking habits,
      alcohol consumption, physical activity, school attendance, household income, body
      weight and height, triglyceride, and serum cholesterol was obtained. Full-mouth
      probing depth (PD), clinical attachment loss (CAL), bleeding on probing (BOP),
      and alveolar bone level (ABL) on radiographs were registered. ABL was stratified
      into ABL1=ABL<or=2 mm; ABL2=ABL>2 to <or=4 mm; and ABL3=ABL>4 mm. Multiple
      logistic regression models with stepwise backward elimination were used allowing
      variables with P<0.15 to enter the multivariate analysis. RESULTS: The CHD group
      had a significantly lower outcome with respect to PD, BOP, CAL, and ABL. For
      participants<60 years old, only risk factors such as smoking and diabetic status
      entered the multivariate analysis. For the ABL3 group, there was a significant
      association with CHD for participants<60 years old, the odds ratio being 6.6
      (1.69 to 25.6). For participants>or=60 years old, there was no association.
      CONCLUSIONS: The present study showed a positive association between periodontal
      disease and CHD in agreement with several other studies. The association was
      highly age dependent and could only be attributed to diabetes and smoking to some
      extent.

PMID- 16945034
TI  - Osteoinductive ability of human allograft formulations.
AB  - BACKGROUND: Bone graft materials are needed in periodontics that are
      osteoinductive, have good handling characteristics, and have physical properties
      that provide appropriate stiffness for the treatment site. Demineralized freeze
      dried bone allograft (DFDBA), also called demineralized bone matrix (DBM), is
      osteoinductive but requires a carrier to meet the other clinical objectives,
      thereby decreasing the DBM content per volume of the bone graft material. The
      present study determined whether the DBM content of a carrier formulation is an
      important variable with respect to its effectiveness as an osteoinductive
      material. METHODS: The immunocompromised Nu/Nu mouse-muscle implantation assay of
      osteoinductivity was used to test human DBM formulated with hyaluronic acid (HY)
      and cancellous and cortical bone granules from the same donor: DBM alone (11 mg);
      DBM (11 mg):HY, 55:45, weight/weight (wt/wt); DBM (6.4 mg):HY, 32:68, wt/wt; DBM
      mixed with cortical and cancellous bone chips 1:4 (DBMC) (11 mg total, of which
      2.2 mg was DBM); DBMC (11 mg):HY, 55:45, wt/wt; heat-treated DBM (11 mg); HY
      alone; and positive-control DBM (11 mg). Osteoinduction was scored using a
      qualitative scale and by histomorphometry. RESULTS: Results showed that all DBM
      was osteoinductive and the addition of HY did not change this as long as the
      amount of DBM used was held constant. The reduction in the absolute amount of DBM
      resulted in a reduced osteoinduction score, reduced ossicle area, and reduced new
      bone formation. The addition of HY also caused a decrease in the amount of
      residual non-vital bone particles, particularly when DBMC was implanted. Results
      were donor dependent. CONCLUSION: This study showed the importance of DBM content
      and donor variability in osteoinductivity of DBM formulations with improved
      handling and stiffness characteristics.

PMID- 16945035
TI  - Salivary histamine level as a predictor of periodontal disease in type 2 diabetic
      and non-diabetic subjects.
AB  - BACKGROUND: Some previous investigations underscored the role of histamine in
      periodontal disease, especially in diabetic patients, but the behavior of this
      inflammatory mediator in the early phases of periodontal involvement remains
      unclear. The aim of the present study was to correlate the presence of histamine
      in saliva with clinical parameters in healthy, periodontitis-affected, and
      diabetic subjects to ascertain whether this amine may serve as a predictive index
      of periodontal risk. METHODS: For this purpose, subjects were selected as
      follows: 1) with newly diagnosed type 2 diabetes mellitus; 2) with neither
      diabetes nor periodontitis; 3) with no diabetes but with chronic, untreated
      periodontal disease. Histamine salivary levels were measured at the initial time
      (T0) and after 6, 12, and 24 months using high-performance liquid chromatography.
      The main periodontal indexes were recorded at the same time intervals. RESULTS:
      At T0, a very typical shape of the histamine chromatogram was found for all
      patients of the three groups; at this time, the salivary histamine levels of
      diabetic patients were increased and comparable to those of healthy patients with
      periodontal disease, whereas healthy subjects with no periodontitis showed
      reduced histamine levels. Further controls at 6, 12, and 24 months showed a
      statistically significant correlation between the increase of salivary histamine
      and the worsening of the periodontal indexes in diabetic and non-diabetic
      subjects. CONCLUSION: These results suggest that salivary histamine may serve as
      a predictive index in the prevention of periodontal disease.

PMID- 16945036
TI  - The diagnosis of periodontal disease in private practice.
AB  - BACKGROUND: Periodontal disease is an inflammatory reaction to the bacteria in
      dental plaque. The present study compared the prevalence of periodontal disease
      in patients using as a diagnostic either probing depth measurements, an
      inflammatory marker such as numbers of white blood cells in plaque samples, or
      microbiological markers such as the microscopic count and the benzoyl-DL-arginine
      naphthylamide (BANA) test. METHODS: Teeth with the most inflammation and/or
      deepest pockets in each quadrant were probed and subgingival plaque was sampled
      from 1,043 consecutive new patients enrolled in a private practice. Multivariate
      "diagnostic" models were developed based upon the probing depth (general linear
      models), percentage of white blood cell-positive and percentage of BANA-positive
      plaques (logistic regression models) to determine the prevalence of patients with
      periodontal disease. RESULTS: Plaque samples were removed from 3,694 sites. Fifty
      two percent of sampled pockets were >4 mm; 49% of sites were inflamed, using the
      presence of white blood cells, and 28% were infected using the BANA test.
      Diagnostic models were highly significant at P<0.0001. The white blood cell model
      was the most parsimonious as demonstrated by the lowest Akaike information
      criteria statistic and had the highest receiver operator characteristic (ROC)
      curve relative to the probing depth and BANA models. CONCLUSIONS: Periodontal
      disease can be diagnosed chairside by the presence of white blood cells in plaque
      samples, a finding that reflects the inflammatory nature of the disease process.
      This approach would reduce the misclassification of subjects as having
      periodontal disease (130 patients in the present study who had pockets) but
      minimal evidence of an inflammatory response.

PMID- 16945037
TI  - Superior effect of MD05, beta-tricalcium phosphate coated with recombinant human
      growth/differentiation factor-5, compared to conventional bone substitutes in the
      rat calvarial defect model.
AB  - BACKGROUND: MD05 consists of beta-tricalcium phosphate (beta-TCP) coated with
      recombinant human growth/differentiation factor-5 (rhGDF-5) and is under
      evaluation as an osteoinductive and osteoconductive bone graft material for use
      in dental and maxillofacial applications. The objective of this study was to
      compare the bone regenerative properties of MD05 with those of conventional
      commercially available bone substitutes. METHODS: Full-thickness, 6-mm diameter,
      calvarial critical-size defects (two per animal) were created in adult Sprague
      Dawley rats. Groups of rats were implanted with the following: 1) MD05; 2) bovine
      bone mineral; 3) bovine bone mineral with collagen; 4) bovine bone mineral with
      synthetic peptide, 5) beta-TCP (from two different manufacturers); or 6) no
      filling material (sham controls). Blinded macroscopic analysis, histopathologic
      analysis, and histomorphometric analysis were carried out 6 weeks after
      implantation. RESULTS: New bone formation assessed histomorphometrically was
      about five times greater with MD05 than with the other bone substitutes tested,
      and bone repair was well advanced in MD05-filled defects after 6 weeks. The
      extent of fibrous tissue and residual implant were significantly lower in the
      MD05 group. In contrast to the other materials, the use of MD05 was associated
      with the complete osseous bridging of the defect and with the presence of normal
      bone marrow. The osteoinductive effect of rhGDF-5 was apparent from the more
      pronounced bone ingrowth observed with MD05 compared to the beta-TCP carrier
      alone. All implants showed good biocompatibility. CONCLUSION: MD05 achieved
      superior bone regeneration compared to conventional materials and is a promising
      new bone substitute for dental and maxillofacial applications.

PMID- 16945038
TI  - A short-term clinical and microbial evaluation of periodontal therapy associated
      with amalgam overhang removal.
AB  - BACKGROUND: This study evaluated the effect of periodontal therapy plus amalgam
      overhang removal (PT+AOR) on periodontal status and the presence of
      Actinobacillus actinomycetemcomitans and Streptococcus mutans and compared two
      microbiological sampling techniques. METHODS: Molar teeth with Class II overhang
      restorations were selected as the test group, and homologous sound teeth were
      selected as the control group. Periodontal probing depth (PD), clinical
      attachment level (CAL), and plaque and gingival indices were measured, and
      restorations were evaluated using radiographs and clinical exploration at
      baseline (T1) and 90 days after PT+AOR (T2). Microbial samples were taken with
      dental floss and paper points at T1 and T2. S. mutans and A.
      actinomycetemcomitans were detected using culture and commercial kits. RESULTS:
      Mean values of plaque and gingival indices did not show statistically significant
      differences between test and control teeth between T1 and T2. At T2, the mean CAL
      decreased among test teeth, and the number of test teeth positive for A.
      actinomycetemcomitans showed a decrease, whereas positive samples for S. mutans
      increased. At T1, an association between the two sampling techniques for both
      bacteria was found. At T2, dental floss presented low sensitivity values for A.
      actinomycetemcomitans, whereas paper points showed low sensitivity for S. mutans.
      CONCLUSIONS: PT+AOR showed a beneficial effect on clinical parameters and a
      decrease of A. actinomycetemcomitans. At T1, both sampling techniques showed
      appropriate results. At T2, the use of paper points was a more sensitive sampling
      technique for isolate A. actinomycetemcomitans, whereas dental floss was found to
      be an alternative sampling method for isolate S. mutans.

PMID- 16945039
TI  - Reevaluation of initial therapy: when is the appropriate time?
AB  - The concept of periodontal reevaluation of initial therapy needs to be revisited.
      From interviewing selective periodontists and reviewing the literature, it is
      apparent that the time period to perform a reevaluation is an ambiguous topic.
      This seems to be a dichotomy because today everything in dental medicine and
      medicine is evidence based. When reviewing selective literature sources, it was
      found that either a time period for reevaluation was given that was different in
      almost every publication, or a time period was not given but the subject of
      reevaluation was addressed. The objective of this commentary is to define
      reevaluation and to determine the best time interval after initial therapy to
      perform a reevaluation based on classic and current literature. Some questions
      that need to be addressed are the following: 1) Does too short of a time frame
      for reevaluation lead to the overtreatment of patients? 2) Is there a danger in
      reevaluating over too long of a time frame that will lead to disease progression
      and the return of pathogenic microbial flora? This would mean unnecessary
      periodontal breakdown could be occurring without appropriate further treatment.
      Many concerns need to be addressed, including when the appropriate time period is
      to measure the effects of initial therapy. After this time period, the stability
      of the periodontium should be evaluated rather than the effects of therapy.

PMID- 16945041
TI  - Guidelines for the management of patients with periodontal diseases.

PMID- 16945040
TI  - Paradental cyst: report of two cases.
AB  - BACKGROUND: The paradental cyst is an odontogenic lesion of inflammatory origin
      that has few clinical signs and symptoms apart from recurring acute episodes. A
      well-defined radiolucency associated with the roots or distal to the crown may be
      seen radiographically. The purpose of this article is to report on different
      aspects of two cases involving paradental cysts. In the first case, the patient
      complained about recurring pericoronitis. A semilunar-shaped radiolucency on the
      distal aspect of the mandibular third molar was noted on the periapical
      radiograph. In the second case, the patient's main complaint was chronic trauma
      of the overlying mucosa. Radiographs revealed an enlarged pericoronal space.
      METHODS: In both cases, the mandibular third molar was extracted due to a lack of
      space. Lesional samples were sent for histopathologic analysis. RESULTS: In the
      first case, the drainage of cystic fluid and a regular concavity were found
      during tooth removal. In the second case, a nodular lesion was found adhering to
      the disto-buccal surface of the tooth arising from the distal wall of a
      periodontal pocket. The histopathologic analysis revealed a hyperplastic
      stratified squamous epithelium with arcading lining a fibrous capsule with
      inflammatory infiltrate, resulting in a final diagnosis of a paradental cyst.
      CONCLUSIONS: The presence of a paradental cyst should be considered when
      recurrent inflammatory periodontal processes are associated with partially
      erupted vital teeth, even when characteristic radiographic findings are absent.
      Definitive diagnosis requires a clinicopathologic correlation incorporating
      surgical, radiographic, and histologic findings.

PMID- 16945042
TI  - International adoption: issues in infectious diseases.
AB  - International adoptions have become increasingly common in the United States.
      Children awaiting international adoption and families traveling to adopt these
      children can be exposed to a variety of infectious diseases. Compared with the
      United States, foreign countries often have different immunization practices and
      methods of diagnosing, treating, and monitoring disease. Reporting of medical
      conditions can also differ from that of the United States. The prevalence of
      infectious diseases varies from country to country and may or may not be common
      among adopted children. The transmission of tuberculosis, hepatitis B, and
      measles from adopted children to family members has been documented. Furthermore,
      infectious organisms (e.g., intestinal parasites), bacterial pathogens (e.g.,
      Bordetella pertussis and Treponema pallidum), and viruses (e.g., human
      immunodeficiency virus and hepatitis viruses) may cause clinically significant
      morbidity and mortality among infected children. Diseases such as severe acute
      respiratory syndrome or avian influenza have not been reported among
      international adoptees, but transmission is possible if infection is present.
      Family members may be infected by others during travel or by their adopted child
      after returning home. Families preparing to adopt a child from abroad should pay
      special attention to the infectious diseases they may encounter and to the
      precautions they should take on returning home.

PMID- 16945043
TI  - Development and validation of the pediatric nausea assessment tool for use in
      children receiving antineoplastic agents.
AB  - STUDY OBJECTIVE: To develop and validate an instrument to assess nausea intensity
      in children aged 4-18 years. DESIGN: Prospective, descriptive study. SETTING:
      Tertiary-quaternary, university-affiliated pediatric hospital. PATIENTS: Four
      pediatric inpatient groups (177 patients): group 1 (107), those receiving cancer
      chemotherapy; group 2 (24), those receiving cancer chemotherapy before
      hematopoietic stem cell transplantation; group 3 (23), those with cancer who were
      not receiving cancer chemotherapy; and group 4 (23), those without cancer.
      INTERVENTION: We developed a scale with a standard script for administration, the
      Pediatric Nausea Assessment Tool (PeNAT). Revisions were made after face validity
      testing with clinicians and parents, and pilot testing with 15 inpatients
      undergoing chemotherapy. MEASUREMENTS AND MAIN RESULTS: The PeNAT scores were
      obtained 4-24 hours after chemotherapy in groups 1 and 2. Dietary intake scores
      and number of emetic episodes were recorded for the 4 hours before PeNAT
      administration for all patients in group 2 and 36 patients in group 1. Parents of
      a subset of patients made an independent assessment of their child's nausea and
      pain intensities immediately before PeNAT administration. Reliability was
      evaluated in groups 1 and 2 by correlating the first and second (obtained 1 hr
      after the first) PeNAT scores. Construct validity was evaluated by comparing
      PeNAT scores in groups 1-4. Criterion-related validity was evaluated by
      correlating PeNAT scores with emetic episodes and dietary intake. Convergent and
      discriminant validity were evaluated by correlating PeNAT scores with parental
      assessments of nausea and pain. Significant differences in PeNAT scores were
      noted among the study groups (p=0.035). Moderate correlation was noted between
      the first and second PeNAT scores (Spearman rho = 0.649). The PeNAT scores
      correlated modestly with emetic episodes (Spearman rho = 0.322) but not with
      dietary intake (Spearman rho = -0.217). Children's PeNAT scores correlated
      moderately with their parents' assessment of nausea (Spearman rho = 0.442),
      whereas little correlation was seen between children's PeNAT scores and parents'
      assessment of pain (Spearman rho = 0.167). CONCLUSION: The PeNAT is a new
      instrument that can be used by children to assess nausea intensity.

PMID- 16945044
TI  - Limited sampling strategy for predicting area under the concentration-time curve
      of mycophenolic acid in adult lung transplant recipients.
AB  - STUDY OBJECTIVE: To develop limited sampling strategies for estimation of
      mycophenolic acid exposure (by determining area under the concentration-time
      curve [AUC]) in lung transplant recipients by using sampling times within 2 hours
      after drug administration and a maximum of three plasma samples. DESIGN:
      Prospective, open-label clinical study. SETTING: Lung transplant clinic in
      Vancouver, British Columbia, Canada. PATIENTS: Nineteen adult (mean age 48.3 yrs)
      lung transplant recipients who were receiving mycophenolate mofetil therapy along
      with cyclosporine (9 patients) or tacrolimus (10 patients). INTERVENTION: Eleven
      blood samples were collected from each of the 19 patients over 12 hours:
      immediately before (0 hr) and 0.3, 0.6, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours
      after administration of mycophenolate mofetil. MEASUREMENTS AND MAIN RESULTS:
      Mycophenolic acid levels in plasma were determined by a high-performance liquid
      chromatography-ultraviolet detection method. The 19 patients were randomly
      divided into index (10 patients) and validation (9 patients) groups. Limited
      sampling strategies were developed with multiple regression analysis by using
      data from the index group. Data from the validation group were used to test each
      strategy. Bias and precision of each limited sampling strategy were determined by
      calculating the mean prediction error and the root mean square error,
      respectively. The correlation between AUC and single concentrations was generally
      poor (r2= 0.18-0.73). Two single-concentration strategies, eight two
      concentration strategies, and eight three-concentration strategies matched our
      criteria. However, the best overall limited sampling strategies (and their
      predictive performance) were the following: log AUC = 0.241 log C0 + 0.406 log C2
      + 1.140 (bias -5.82%, precision 5.97%, r2= 0.828) and log AUC = 0.202 log C0 +
      0.411 log C1.5 + 1.09 (bias -5.71%, precision 6.94%, r2= 0.791), where Cx is
      mycophenolic acid concentration at time x hours. CONCLUSION: Two-concentration
      limited sampling strategies provided minimally biased and highly precise
      estimation of mycophenolic acid AUC in lung transplant recipients. These optimal
      and most clinically feasible limited sampling strategies are based collectively
      on the number of blood samples required, r2 value, bias, and precision.

PMID- 16945045
TI  - Electrocardiographic and blood pressure effects of the ephedra-containing TrimSpa
      thermogenic herbal compound in healthy volunteers.
AB  - STUDY OBJECTIVE: To determine the effect of an ephedra-containing thermogenic
      herbal compound (TrimSpa) on rate-corrected QT (QTc) interval duration and
      systolic blood pressure. DESIGN: Randomized, double-blind, placebo-controlled,
      crossover, intent-to-treat study. SETTING: Student laboratory at a college of
      pharmacy. SUBJECTS: Thirteen healthy volunteers (eight men, five women).
      INTERVENTION: Participants were given TrimSpa, which contains more than 30
      ingredients including ephedra 15 mg and caffeine 60 mg, or matching placebo 3
      times/day for 7 days in a crossover fashion with a 7-day washout period between
      treatments. MEASUREMENTS AND MAIN RESULTS: Each subject's QTc interval and
      systolic blood pressure were measured on days 1, 4, and 7. These measurements
      were performed immediately before study drug ingestion (baseline) and 0.5, 1, and
      3 hours after ingestion. No differences in these variables were found between the
      TrimSpa and placebo groups. In one subject taking TrimSpa, the QTc interval
      increased 96 msec from baseline, more than double the largest increase in the
      placebo group. CONCLUSION: Standard doses of TrimSpa did not induce changes in
      subjects' QTc intervals or systolic blood pressures. However, because the QTc
      interval dramatically changed in one subject taking TrimSpa, a large study is
      needed to determine if the effect is an artifact or if the subject represents a
      subset of people for whom the drug may pose a risk.

PMID- 16945046
TI  - Discordant beta-blocker effects on clinic, ambulatory, resting, and exercise
      hemodynamics in patients with hypertension.
AB  - STUDY OBJECTIVES: To determine the correlation between ambulatory and clinic
      blood pressure in assessing antihypertensive response to beta-blockade, to test
      whether blood pressure response to metoprolol is associated with the heart rate
      response, and to determine whether exercise and resting heart rate responses to
      metoprolol are correlated. DESIGN: Post hoc analysis of a prospective cohort
      study. SETTING: University-affiliated general clinical research center. PATIENTS:
      Fifty-one patients aged 35-65 years with uncomplicated hypertension.
      Intervention. All patients received metoprolol at a dosage titrated to achieve a
      diastolic blood pressure below 90 mm Hg. MEASUREMENTS AND MAIN RESULTS: Clinic
      and 24-hour ambulatory blood pressure measurements were obtained and exercise
      treadmill testing was performed before and after metoprolol treatment. Based on
      ambulatory blood pressure data, 24 patients (47%) responded (defined as at least
      a 10% reduction in diastolic blood pressure) to metoprolol compared with 36
      patients (71%) based on clinic blood pressure data (p=0.027). Clinic blood
      pressure was associated with a 67% false-positive rate (responsive blood pressure
      by clinic data that was actually nonresponsive by ambulatory data). Blood
      pressure responders and nonresponders exhibited similar reductions in exercise
      heart rate (24% and 23%, p=0.74). However, responses to metoprolol measured by
      exercise heart rate versus resting heart rate were not significantly correlated
      (r=0.24, p=0.105). CONCLUSION: Reliance on clinic blood pressure or resting heart
      rate for making beta-blocker treatment decisions may yield less than optimal
      assessment of the antihypertensive response or degree of beta-blockade.

PMID- 16945047
TI  - Effect of quercetin on the plasma and intracellular concentrations of saquinavir
      in healthy adults.
AB  - STUDY OBJECTIVES: To determine if quercetin, a bioflavonoid that inhibits p
      glycoprotein, alters plasma saquinavir concentrations, and to explore the
      potential influence on intracellular concentrations. DESIGN: Prospective
      pharmacokinetic analysis. SETTING: University-affiliated general clinical
      research center. SUBJECTS: Ten healthy adults (four women, six men) with a mean
      +/- SD age of 30.7 +/- 9.4 years. INTERVENTION: All subjects received saquinavir
      1200 mg 3 times/day with food on days 1-11 and quercetin 500 mg 3 times/day with
      food on days 4-11. MEASUREMENTS AND MAIN RESULTS: On days 4 and 11, nine blood
      samples and four peripheral blood mononuclear cell samples were drawn during a
      steady-state dosing interval. Pharmacokinetic parameters were calculated by using
      standard noncompartmental techniques. Plasma saquinavir concentrations were
      similar regardless of quercetin administration. Geometric mean ratios for the
      area under the concentration-time curve during an 8-hour dosing interval (AUC0
      8), maximum concentration in the dosing interval, and minimum concentration in
      the dosing interval were 0.99 (95% confidence interval [CI] 0.65-1.50), 0.99 (95%
      CI 0.64-1.54), and 1.06 (95% CI 0.68-1.67), respectively. Intracellular
      saquinavir concentrations displayed substantial intra- and intersubject
      variability, which limited the ability to determine the influence of quercetin
      coadministration (geometric mean ratio for AUC0-8 = 0.51 [95% CI 0.14-1.95], six
      patients). CONCLUSION: Quercetin coadministration did not influence plasma
      saquinavir concentrations. Because of substantial inter- and intrasubject
      variability, more study is necessary to determine if saquinavir intracellular
      concentrations are altered by coadministration of quercetin.

PMID- 16945048
TI  - Use of heparin versus lepirudin flushes to prevent withdrawal occlusion of
      central venous access devices.
AB  - STUDY OBJECTIVE: To determine whether lepirudin flushes are more effective than
      heparinized saline in preventing withdrawal occlusion of central venous access
      devices. DESIGN: Randomized, double-blind clinical trial. SETTING: Research
      institution-tertiary referral center. PATIENTS: Forty-nine adults undergoing bone
      marrow transplantation for hematologic malignancies or metastatic solid tumors.
      INTERVENTION: Twenty-four patients received heparin and 25 received lepirudin
      flushes. The heparin dose was 3 ml of porcine heparin 100 U/ml (300 U) per
      catheter lumen at least once/day; the lepirudin dose was 3 ml of lepirudin 100
      microg/ml (300 microg) per catheter lumen at least once/day. After 3-4 weeks, all
      49 patients received the heparin flushes. MEASUREMENTS AND MAIN RESULTS: Efficacy
      was assessed by the frequency with which the patients were treated with alteplase
      instillations for withdrawal occlusion of their central venous access devices
      during the first 4 months of catheterization. Three (12.5%) patients treated with
      heparin alone and five (20%) treated initially with lepirudin required alteplase
      instillations for an estimated relative risk with lepirudin versus heparin of 1.6
      (95% confidence interval [CI] 0.40-13.86, p=0.70). CONCLUSION: Lepirudin was not
      more effective than heparin, which may have been related to the conservative dose
      of lepirudin administered. However, higher lepirudin doses are likely to incur an
      unacceptable risk of systemic anticoagulation.

PMID- 16945049
TI  - Analysis of the psychoactive terpenoid salvinorin A content in five Salvia
      divinorum herbal products.
AB  - STUDY OBJECTIVE: To determine the content of the hallucinogen salvinorin A in a
      variety of Salvia divinorum herbal products and to compare the content with the
      label claims of potency and purity. DESIGN: Laboratory analysis. SETTING:
      University-affiliated laboratory. SAMPLES: Five herbal products containing Salvia
      divinorum. MEASUREMENTS AND MAIN RESULTS: The samples were purchased from the
      Internet and local drug paraphernalia shops ("head shops"). Highperformance
      liquid chromatography and thin-layer chromatography-gas chromatography-mass
      spectroscopy were used for the analysis. All five samples contained salvinorin A,
      a psychoactive compound found in Salvia divinorum; however, the salvinorin A
      concentrations we measured were much lower than those claimed on the product
      label. Vitamin E was also found in two samples and caffeine in one sample.
      CONCLUSION: The five salvinorin A herbal products were found to be subpotent, and
      three products contained adulterants. Any discrepancy between the advertised
      salvinorin A concentration and their actual concentration may pose a potential
      risk of both misuse and overdose. These concerns, and the recently reported
      teenage suicide that could have been related to salvia consumption, underscore
      the need for practitioners to become familiar with the signs and symptoms of
      salvia use.

PMID- 16945050
TI  - Treatment options for nausea and vomiting during pregnancy.
AB  - Nausea and vomiting, common symptoms during pregnancy, often are regarded as an
      unpleasant but normal part of pregnancy during the first and early second
      trimesters. Nausea and vomiting of pregnancy (NVP) occurs in approximately 75-80%
      of pregnant women. The exact etiology and pathogenesis of NVP are poorly
      understood and are most likely multifactorial. Some theories for the etiology of
      NVP are psychological predisposition, evolutionary adaptation, hormonal stimuli,
      and Helicobacter pylori infection. Treatment ranges from dietary and lifestyle
      changes to vitamins, antiemetics, and hospitalization for intravenous therapy.
      Treatment generally begins with nonpharmacologic interventions; if symptoms do
      not improve, drug therapy is added. Although NVP has been associated with a
      positive pregnancy outcome, the symptoms can significantly affect a woman's life,
      both personally and professionally. Given the substantial health care costs, as
      well as indirect costs, and the potential decrease in quality of life due to NVP,
      providers need to acknowledge the impact of NVP and provide appropriate
      treatment.

PMID- 16945051
TI  - Statin withdrawal: clinical implications and molecular mechanisms.
AB  - Retrospective analyses of data from the Platelet Receptor Inhibition in Ischemic
      Syndrome Management (PRISM), the National Registry of Myocardial Infarction 4,
      and the Global Registry of Acute Coronary Events (GRACE) trials revealed that the
      benefits of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins)
      on acute coronary outcomes are rapidly lost and outcomes worsened if statins are
      discontinued during a patient's hospitalization for an acute coronary syndrome.
      Withdrawal of statin therapy in the first 24 hours of hospitalization for non-ST
      elevation myocardial infarction increased the hospital morbidity and mortality
      rate versus continued therapy (11.9% vs 5.7%, p<0.01). Data from the Treating New
      Targets (TNT) study, however, suggested that short-term discontinuation of statin
      therapy in patients with stable cardiac conditions may not substantially increase
      the risk of acute coronary syndromes. In patients with acute coronary syndromes
      who discontinue statins, the rapid increase in risk of an event may result not
      only from the lost benefits from the therapy, but also from rebound inhibition of
      vascular protective substances and activation of vascular deleterious substances.
      Statins inhibit cholesterol synthesis in vascular cells. By reducing levels of
      isoprenoid intermediates, statins increase the production of nitric oxide and
      downregulate angiotensin II AT(1) receptors, endothelin-1, vascular inflammatory
      adhesion molecules, and inflammatory cytokines. These benefits are rapidly lost
      and often transiently reversed when statins are acutely discontinued. Acute
      removal of pleiotropic effects and rebound vascular dysfunction may be more
      important in an acute coronary event, where inflammation promotes rupture of
      atherosclerotic plaques and inflammatory and prothrombosis markers are present in
      high concentration, than in stable chronic vascular disease. In the absence of
      data from randomized controlled trials, current information suggests that statin
      therapy should be continued, and possibly boosted, during hospitalization for an
      acute coronary syndrome. Because statins are discontinued during the early
      hospitalization of many patients, practitioners must ensure that statins are not
      omitted, unless contraindicated, from the treatment of patients with acute
      coronary syndromes.

PMID- 16945052
TI  - Effect of angiotensin-converting enzyme inhibitors and angiotensin II type 1
      receptor blockers on the rate of new-onset diabetes mellitus: a review and pooled
      analysis.
AB  - The rising prevalence and health burden of diabetes mellitus require that new
      approaches for prevention among high-risk populations be evaluated. Emerging
      evidence from the prospective evaluations of secondary and tertiary outcomes and
      from retrospective evaluations in randomized controlled trials suggests that
      angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 receptor
      blockers (ARBs) may reduce the occurrence of new-onset diabetes. Therefore, we
      each independently searched MEDLINE for randomized controlled trials from January
      1966-October 2005 that used an ACE inhibitor or ARB as a primary intervention
      versus a control group not receiving an ACE inhibitor or ARB and that reported
      the occurrence of diabetes. Thirteen trials were identified. In each of the 13
      studies, the frequency of diabetes in the ACE inhibitor or ARB groups was lower
      than that in the control groups. In addition, it was consistent in that no study
      significantly excluded any benefit from ACE inhibitors or ARBs on the rate of new
      onset diabetes. The combined occurrence of new-onset diabetes in all 13 studies
      was 2249 cases among 31,283 patients (7.2%) in the ACE inhibitor or ARB group
      versus 3230 cases among 35,988 patients (9.0%) in the control group. The combined
      relative risk of diabetes was 0.80, with a 95% confidence interval of 0.76-0.84,
      based on a two-sided alpha of 0.05, in favor of ACE inhibitors and ARBs. This
      observation needs to be confirmed by randomized controlled trials with the
      frequency of diabetes as the primary prospective end point.

PMID- 16945053
TI  - Interaction between selective serotonin reuptake inhibitors and nonsteroidal
      antiinflammatory drugs: review of the literature.
AB  - OBJECTIVE: To evaluate the evidence of an interaction between selective serotonin
      reuptake inhibitors (SSRIs) and nonsteroidal antiinflammatory drugs (NSAIDs)
      producing an increased risk for gastrointestinal adverse outcomes such as
      bleeding. METHODS: We searched MEDLINE for English-language literature published
      between 1966 and August 2005. All studies examining gastrointestinal adverse
      effects from an SSRI-NSAID combination were included. DATA SYNTHESIS: Four
      retrospective studies examined gastrointestinal adverse outcomes from the
      combination of SSRIs and NSAIDs. The risk ratio for an upper gastrointestinal
      bleed from this drug combination (compared with not receiving either agent)
      ranged from 3.3-15.6, and the risk ratio for gastrointestinal adverse effects was
      12.4. Two studies found that the risk for an upper gastrointestinal bleed from
      the drug combination exceeded the additive risk of the agents alone. The risk
      ratio for an upper gastrointestinal bleed from an SSRI-aspirin interaction was
      1.9-7.2. In addition, the number needed to harm in terms of an upper
      gastrointestinal bleed from an SSRI-NSAID combination ranged from 62-75 patient
      years, and the number needed to harm for gastrointestinal adverse effects was 2
      patient-years. CONCLUSION: Concurrent use of an SSRI and NSAID increases the risk
      of gastrointestinal adverse outcomes such as bleeding. Clinicians must take care
      to avoid these negative outcomes by altering NSAID or SSRI therapy, or by
      providing ulcer-protective drugs.

PMID- 16945054
TI  - Interaction between warfarin and cranberry juice.
AB  - Warfarin is extensively used for anticoagulation to a target international
      normalized ratio of 2.0-3.0 for most indications or 2.5-3.5 for high-risk
      indications; however, many drugs and dietary supplements induce fluctuations in
      the international normalized ratio. Such fluctuations may lead to therapeutic
      failure or bleeding complications. Cranberry juice is increasingly used for the
      prevention and adjunctive treatment of urinary tract infections. The United
      Kingdom's Committee on Safety of Medicines has alerted clinicians to a potential
      interaction between warfarin and cranberry juice and has advised that patients
      avoid their concurrent use. Review and analysis of the literature revealed that
      ingestion of large volumes of cranberry juice destabilize warfarin therapy. Small
      amounts of juice are not expected to cause such an interaction. Clinicians should
      be aware of this potential interaction and monitor and counsel patients
      accordingly.

PMID- 16945055
TI  - Application of antimicrobial pharmacodynamic concepts into clinical practice:
      focus on beta-lactam antibiotics: insights from the Society of Infectious
      Diseases Pharmacists.
AB  - In recent years there have been tremendous strides in understanding the
      relationship between the pharmacodynamics of beta-lactams and microbiologic
      response. For beta-lactams, in vitro and animal studies suggest that the amount
      of time in which free or non-protein-bound antimicrobial concentration exceeds
      the minimum inhibitory concentration (MIC) of the organism (fT>MIC) is the best
      predictor of bacterial killing and microbiologic response. Using population
      pharmacokinetic modeling and Monte Carlo simulation, it is possible to integrate
      pharmacokinetics, a pharmacodynamic target, and microbiologic surveillance data
      to generate empiric beta-lactam dosing strategies that maximize the likelihood of
      achieving fT>MIC associated with near maximal bactericidal effect against the
      range of pathogens encountered in clinical practice. At Albany Medical Center
      Hospital, these mathematical modeling techniques were used to devise alternative
      dosing schemes for piperacillin-tazobactam, meropenem, and cefepime. These
      alternative schemes optimized fT>MIC at a lower total daily dose than would be
      employed with traditional dosing methods. Moreover, they achieved the targeted
      fT>MIC with less administration time/day than would be needed for continuous
      infusion.

PMID- 16945056
TI  - Coronary artery disease and hypertension: outcomes of a pharmacist-managed blood
      pressure program.
AB  - STUDY OBJECTIVE: To assess the effectiveness of a pharmacist-managed service in
      improving hypertension control among patients with coronary artery disease.
      DESIGN: Prospective cohort study. Setting. Health maintenance organization.
      PATIENTS: Three hundred seventy-six patients with uncontrolled hypertension and
      coronary artery disease. INTERVENTION: Pharmacist-managed, physician-supervised
      population-management approach to optimize evidence-based drug management.
      MEASUREMENTS AND MAIN RESULTS: Blood pressure reduction and control were
      evaluated, as well as the use of angiotensin-converting enzyme inhibitors and
      generic antihypertensive drugs during 7-month follow-up. At baseline, mean +/- SD
      age was 70.4 +/- 8.8 years, 247 (65.7%) were men, 201 (53.5%) had a history of
      myocardial infarction, and 237 (63.0%) had diabetes mellitus. Baseline mean
      systolic blood pressure was 151 mm Hg, and none had achieved their blood pressure
      goal. During follow-up, mean systolic blood pressure decreased 16.1 mm Hg overall
      (p<0.001), and 179 (47.6%) patients achieved their goal blood pressure (p<0.001).
      Blood pressure reductions were 14.7 and 18.4 mm Hg in patients with and patients
      without diabetes, respectively (p<0.001). The target dose for angiotensin
      converting enzyme inhibitors was achieved in 252 (67.0%) patients compared with
      102 (27.1%) at baseline (p<0.001). Generic fill rates for antihypertensive drugs
      continued to be higher than 95% during follow-up (p=0.723). CONCLUSION: A
      pharmacist-managed, physician-supervised population-management approach in
      patients with coronary artery disease significantly improved blood pressure
      control. Clinically meaningful reductions in blood pressure were achieved by
      using evidence-based, cost-effective drug regimens.

PMID- 16945057
TI  - Effectiveness of a two-part educational intervention to improve hypertension
      control: a cluster-randomized trial.
AB  - STUDY OBJECTIVE: To measure the effectiveness of a multifaceted educational
      intervention to improve ambulatory hypertension control. DESIGN: Cluster
      randomized trial. SETTING: Academic health system using an ambulatory electronic
      medical record. SUBJECTS: A total of 10,696 patients with a diagnosis of
      hypertension cared for by 93 primary care providers. INTERVENTION: Academic
      detailing, provision of provider-specific data about hypertension control,
      provision of educational materials to the provider, and provision of educational
      and motivational materials to patients. MEASUREMENTS AND MAIN RESULTS: The
      primary outcome was blood pressure control, defined as a blood pressure
      measurement below 140/90 mm Hg, and was ascertained from electronic medical
      records over 6 months of follow-up. We determined the adjusted odds ratio for the
      association between the intervention and the achievement of controlled blood
      pressure. When we accounted for clustering by provider, this adjusted odds ratio
      was 1.13 (95% confidence interval 0.87-1.47). Adjusted odds ratios were 1.03 (95%
      confidence interval 0.78-1.36) in patients whose blood pressure was controlled at
      baseline and 1.25 (95% confidence interval 0.94-1.65) in those whose blood
      pressure was not. These odds ratios were not significantly different (p=0.11).
      CONCLUSIONS: These results were consistent with no effect or, at best, a
      relatively modest effect of the intervention among patients with hypertension.
      Had we not included a concurrent control group, the data would have provided an
      unduly optimistic view of the effectiveness of the program. The effectiveness of
      future interventions may be improved by focusing on patients whose blood pressure
      is uncontrolled at baseline.

PMID- 16945058
TI  - Acute renal failure during lisinopril and losartan therapy for proteinuria.
AB  - The use of combined therapy with an angiotensin-converting enzyme (ACE) inhibitor
      and an angiotensin II receptor blocker (ARB) for treatment of proteinuria has
      been gaining support. Limited data are available regarding this treatment in the
      pediatric population. This report describes a case of acute compromise of renal
      function associated with hypotension in a 7-year-old boy treated with the ACE
      inhibitor lisinopril and the ARB losartan. It emphasizes the need for close
      surveillance of renal function and blood pressure during such therapy even in
      patients with relative preservation of renal function. Further investigation into
      the utility and safety of dual therapy with an ACE inhibitor plus an ARB in
      pediatric patients is warranted. Key Words: renal failure, proteinuria,
      angiotensin-converting enzyme inhibitor, ACEI, angiotensin II receptor blocker,
      ARB.

PMID- 16945059
TI  - Probable association between ziprasidone and worsening hypertension.
AB  - According to premarketing studies, at least 1% of ziprasidone-treated patients
      exhibited hypertension; however, this figure is not necessarily attributable to
      the drug. A PubMed/MEDLINE search yielded no articles describing hypertension as
      a possible adverse event associated with oral ziprasidone therapy. We describe a
      53-year-old African-American woman with hypertension and schizophrenia whose
      blood pressure increased during ziprasidone therapy. She experienced no similar
      blood pressure increases during therapy with four other atypical antipsychotics.
      Her mean systolic blood pressure during ziprasidone treatment (158 mm Hg) was
      significantly higher than before (141 mm Hg) and after (135 mm Hg) treatment.
      Also, her mean diastolic blood pressure during ziprasidone treatment (88 mm Hg)
      was significantly higher than after treatment (79 mm Hg). Linear regression
      analysis demonstrated that the patient's systolic blood pressure increased
      significantly with ziprasidone dose (regression coefficient [B] = 0.22 mm Hg x
      day/mg, 95% confidence interval 0.10-0.34, p=0.001). Thus, after adjusting for
      the effect of antihypertensive doses, an increase of 40 mg/day in ziprasidone
      yielded an increase of 8.8 mm Hg in systolic blood pressure. For unknown (perhaps
      genetic) reasons, this patient may have been particularly sensitive to
      ziprasidone. Clinicians prescribing ziprasidone in patients with hypertension
      should be aware that their hypertension could worsen with the addition of
      ziprasidone. If this occurs, replacement of ziprasidone with a different
      antipsychotic should be considered.

PMID- 16945060
TI  - Critical pathways: the role of pharmacy today and tomorrow.

PMID- 16945061
TI  - Review of guidelines and the literature in the treatment of acute bronchospasm in
      asthma.
AB  - Asthma is a common chronic condition that disproportionately affects persons
      younger than 45 years. Asthma exacerbations can be sudden and severe, requiring
      treatment in the emergency department or hospitalization. Children younger than
      15 years are 2-4 times more likely to have asthma as the first-listed hospital
      discharge diagnosis compared with those in other age groups. An estimated 12.8
      million missed school days and 24.5 million lost work days due to asthma occurred
      in 2003. Drugs used in the treatment of acute asthma include inhaled beta(2)
      agonists, oral corticosteroids, and inhaled anticholinergics. Levalbuterol was
      evaluated in several recent trials for treatment of asthma in the emergency
      department, for its effect in improving pulmonary function and on hospitalization
      rate. Theophylline, intravenous beta(2)-agonists, intravenous magnesium sulfate,
      and inhaled anesthetics have not been proven useful in the emergency management
      of asthma. The effectiveness of inhalation devices is dependent on age,
      cooperation of the patient, and technique.

PMID- 16945062
TI  - Review of guidelines and the literature in the treatment of acute bronchospasm in
      chronic obstructive pulmonary disease.
AB  - In 2002, an estimated 11.2 million adults in the United States had chronic
      obstructive pulmonary disease (COPD). Guidelines for the management of the
      disease have been published by the Global Initiative for Chronic Obstructive Lung
      Disease (GOLD) and the American Thoracic Society-European Respiratory Society.
      Several other organizations are in the process of preparing guidelines for COPD,
      most based on the GOLD report. The most important pharmacologic intervention in
      COPD is treatment with bronchodilator drugs. This intervention applies not only
      to stable COPD, but also to exacerbations (flares) of the disease. Prevention
      strategies have been developed for acute exacerbations, and management strategies
      include using short-acting beta(2)-agonists, systemic corticosteroids, and
      antibiotics, in both at home and hospital settings.

PMID- 16945063
TI  - Risk versus benefit considerations for the beta(2)-agonists.
AB  - Short-acting beta(2)-agonists are the mainstay of therapy for acute bronchospasm
      associated with asthma and chronic obstructive pulmonary disease, whereas long
      acting beta(2)-agonists are used in maintaining disease control in these
      respiratory disorders. This review describes and compares the pharmacology of the
      beta(2)-agonists and explains how these differences translate into differences in
      efficacy and beta(2)-adrenergic-mediated adverse effects. Questions commonly
      asked by clinicians regarding the efficacy and safety of short- and long-acting
      beta(2)-agonists include issues about cardiovascular effects, tolerance to their
      bronchodilator and bronchoprotective effects, blunting of albuterol response by
      long-acting beta(2)-agonists, potential masking of worsening asthma control, and
      the role of long-acting beta(2)-agonists as adjunctive therapy with inhaled
      corticosteroids in maintaining asthma control. Pharmacogenetics may play a role
      in determining which patients may be at risk for a reduced response to a beta(2)
      agonist. The continued use of racemic albuterol, which contains a mixture of R
      albuterol and S-albuterol, has been questioned because of data from preclinical
      and clinical studies suggesting that S-albuterol causes proinflammatory effects
      and may increase bronchial hyperreactivity. The preclinical and clinical effects
      of these two stereoisomers are reviewed. Data describing the efficacy and safety
      of levalbuterol (R-albuterol) and racemic albuterol are presented.

PMID- 16945064
TI  - Outcomes and humanistic issues related to treatment of acute bronchospasm.
AB  - Because of emergency department visits and hospitalizations, the economic costs
      associated with asthma, chronic obstructive pulmonary disease (COPD), and
      bronchospasm are a significant portion of total overall treatment costs. A small
      proportion of patients account for most of the costs, due to disease severity and
      acute exacerbations. Disease management programs, sponsored by insurance groups
      and employers, are lowering health and disability costs and reducing days missed
      from work and school because of exacerbations. Quality-of-life patient
      assessments are available to assist practitioners in evaluating disease status.
      Evidenced-based medicine analysis can show that less expensive therapies are not
      necessarily cost-effective. A study of the rate of hospital admissions from the
      emergency department showed that although levalbuterol therapy in the emergency
      department was more costly than racemic albuterol therapy, total overall
      treatment costs were reduced because of decreased hospitalizations in the
      levalbuterol-treated patients. Thus, providers, payers, and patients should
      examine all the scientific evidence (safety, efficacy or effectiveness,
      economics, and humanistic benefits) to make the most informed health care
      decision.

PMID- 16945065
TI  - The value of care algorithms.
AB  - The use of protocols or care algorithms in medical facilities has increased in
      the managed care environment. The definition and application of care algorithms,
      with a particular focus on the treatment of acute bronchospasm, are explored in
      this review. The benefits and goals of using protocols, especially in the
      treatment of asthma, to standardize patient care based on clinical guidelines and
      evidence-based medicine are explained. Ideally, evidence-based protocols should
      translate research findings into best medical practices that would serve to
      better educate patients and their medical providers who are administering these
      protocols. Protocols should include evaluation components that can monitor,
      through some mechanism of quality assurance, the success and failure of the
      instrument so that modifications can be made as necessary. The development and
      design of an asthma care algorithm can be accomplished by using a four-phase
      approach: phase 1, identifying demographics, outcomes, and measurement tools;
      phase 2, reviewing, negotiating, and standardizing best practice; phase 3,
      testing and implementing the instrument and collecting data; and phase 4,
      analyzing the data and identifying areas of improvement and future research. The
      experiences of one medical institution that implemented an asthma care algorithm
      in the treatment of pediatric asthma are described. Their care algorithms served
      as tools for decision makers to provide optimal asthma treatment in children. In
      addition, the studies that used the asthma care algorithm to determine the
      efficacy and safety of ipratropium bromide and levalbuterol in children with
      asthma are described.

PMID- 16945066
TI  - Acute bronchospasm from the patient's perspective: role of patient education.
AB  - Patient education is a vital tool for managing patients with acute bronchospasm
      arising from both asthma and chronic obstructive pulmonary disease (COPD). Both
      are serious chronic diseases, and lack of patient education usually results in
      lack of patients' adherence to their therapies. Several surveys indicate that a
      tremendous disparity exists between physicians and patients with asthma in how
      they perceive control of the patient's lung disease. A high proportion of
      physicians report that they provide patient education, and a low proportion of
      patients claim to have received adequate education. Management plans for both
      asthma and COPD are outlined, including instructions for the use of peak-flow
      meters and profiles of inhalation devices. Although inhalation devices will
      continue to be the most common delivery systems for airway diseases that cause
      acute bronchospasm, their proper use can be both complex and diverse. Patient
      education, therefore, is essential for optimal benefit from therapy.

PMID- 16945067
TI  - The role of pharmacists in the evolution of health care: an open forum
      discussion.
AB  - The pharmacy profession should be actively involved in the development of
      guidelines and protocols for various disease states. Good research to demonstrate
      that interventions by pharmacists result in good clinical outcomes and money
      saved is scarce. Pharmacy is in the early throes of change as a result of growth
      within the profession. In the future, pharmacists will be more involved in
      clinical evaluations and less with drug dispensing duties because of advances in
      automation. The new Medicare Part D program is a real opportunity for pharmacists
      to be actively engaged in patient education and treatment monitoring.

PMID- 16945068
TI  - Treatment algorithms from the pharmacist perspective.
AB  - Hospitals across the United States develop treatment algorithms for acute
      bronchospasm, asthma, and chronic obstructive pulmonary disease by following
      several different pathways. Some institutions use established national guidelines
      and protocols, some revise national guidelines to apply to their particular
      environment, and others create specific institution-related treatment algorithms
      with input from various departments, such as emergency medicine, respiratory
      therapy, and pharmacy. Although some institutions track outcomes on either a
      formal or an informal basis, others have not yet implemented outcomes-based
      programs.

PMID- 16945069
TI  - Regulation of mammalian ciliary beating.
AB  - Recent advances in our understanding of the structure-function relationship of
      motile cilia with the 9 + 2 microtubular arrangement have helped explain some of
      the mechanisms of ciliary beat regulation by intracellular second messengers.
      These second messengers include cyclic adenosine monophosphate (cAMP) and cyclic
      guanosine monophosphate (cGMP) as well as calcium and pH. cAMP activates protein
      kinase A (PKA), which is localized to the axoneme. The cAMP-dependent
      phosphorylation of PKA's main target, originally described as p29 in Paramecium,
      seems to increase ciliary beat frequency (CBF) directly. The mechanism by which
      cGMP increases CBF is less well defined but involves protein kinase G and
      possibly PKA. Protein kinase C inhibits ciliary beating. The regulation
      mechanisms of CBF by calcium remain somewhat controversial, favoring an
      immediate, direct action of calcium on ciliary beating and a second cyclic
      nucleotide-dependent phase. Finally, intracellular pH likely affects CBF through
      direct influences on dynein arms.

PMID- 16945070
TI  - National review of maternity care for women with HIV infection.
AB  - OBJECTIVE: To assess adherence to the British HIV Association (BHIVA) 2001
      guidelines for the management of HIV-infected pregnant women. METHODS: A survey
      and a case note review were carried out using structured questionnaires sent to
      providers of adult HIV care in the UK and Ireland. Participants were women with
      HIV infection who delivered a live or stillborn infant between October 2002 and
      September 2003. The main outcome measures were the appropriate use of
      antiretroviral therapy, the use and timing of elective Caesarean section, and
      support for the avoidance of breast-feeding. RESULTS: Of 186 centres, 100 (54%)
      responded with data on 501 eligible pregnancies. CONCLUSIONS: In general,
      practice was in accordance with the BHIVA 2001 guidelines. However, in a number
      of cases Caesarean sections were planned later than the recommended 38 weeks.

PMID- 16945071
TI  - Demographic predictors of a positive HIV test result among clients attending a
      large metropolitan voluntary counselling and testing centre in Thailand.
AB  - OBJECTIVES: The Thai Red Cross Anonymous Clinic in Bangkok, established in 1991,
      was the first centre in Asia to provide anonymous, voluntary counselling and
      testing for HIV infection. We present outcomes of testing for the period 1997
      2004. METHODS: Newcomers to the Thai Red Cross Anonymous Clinic were invited to
      complete a brief questionnaire concerning HIV risk behaviour and personal
      characteristics. The questionnaire was linked by code numbers to the HIV test
      result. Information obtained from the pretest questionnaire and HIV antibody test
      results from January 1997 to December 2004 were analysed. Data are presented as
      means [with standard deviation (SD)], medians [with interquartile range (IQR)] or
      percentages. Multivariate analysis using logistic regression was performed to
      identify factors predicting a positive HIV test result. RESULTS: Over the 8-year
      study period, 65,807 new clients attended the clinic. Two-thirds were male and
      the mean age was 31.7 years (SD 9 years), and more than half were single. The
      proportion of high-school graduates was 43%, and 36% earned more than 10,000 Baht
      a month (40 Baht:1 US dollar). Of 54,578 new clients who had an HIV test during
      the study period, 17.5% had a positive test result. In multivariate analysis,
      predictive factors for HIV positivity included female gender, age group 25-34
      years, widowed status (women), residence outside Bangkok, birthplace in a
      northern province, no formal schooling, farmer as profession, and salary less
      than 5000 Baht a month (the current legal minimum daily wage set by the Thai
      Ministry of Labor is 181 Baht). CONCLUSIONS: With nearly 7000 clients newly
      tested for HIV infection each year, the Anonymous Clinic in Bangkok has provided
      a unique epidemiological window into the patterns of HIV infection in the Thai
      capital.

PMID- 16945072
TI  - 'Simply forgot' is the most frequently stated reason for missed doses of HAART
      irrespective of degree of adherence.
AB  - OBJECTIVES: Previous studies have reported that forgetfulness is the most
      frequently mentioned reason for missed doses among patients on highly active
      antiretroviral therapy (HAART). However, no previous study has compared the
      reasons given by highly nonadherent patients with the reasons given by patients
      with better adherence. The objective of this study was to examine further
      patients' self-reported reasons for missing doses of HAART and to compare the
      reasons given by patients with lower adherence with those given by patients with
      higher adherence. METHODS: All patients visiting the clinics participating in the
      Danish HIV cohort study during a 1-year period (July 2002 to June 2003) were
      eligible if they had started HAART at least 6 months previously. Consenting
      patients completed an anonymous self-administered questionnaire based upon the
      adult AIDS Clinical Trial Group adherence questionnaires. Lower adherence was
      defined as reporting a missed dose within the preceding 4 days. RESULTS: We
      received usable questionnaires from 840 (75%) of the 1126 eligible patients.
      Patients with lower adherence reported the same reasons for missed doses as
      patients with higher adherence (Spearman's rho=0.952, P<0.0001). In both groups
      of patients the three most frequently reported reasons for missed doses were
      'simply forgot', 'were away from home', and 'had a change in daily routines'.
      CONCLUSIONS: Patients with poorer adherence to HAART state the same reasons for
      missing doses as patients with better adherence, and 'simply forgot' is the most
      frequently stated reason.

PMID- 16945073
TI  - Pulmonary Kaposi sarcoma in the era of highly active antiretroviral therapy.
AB  - OBJECTIVE: Since the introduction of highly active antiretroviral therapy (HAART)
      there has been a dramatic reduction in the incidence of Kaposi sarcoma (KS) and
      an improvement in survival. We wished to examine whether the outcome in pulmonary
      KS (pKS) has also altered. METHODS: In a single-institution cohort of 1140 HIV
      positive patients with KS, 305 patients were diagnosed in the HAART era (1996
      2004). We examined the clinicopathological features and outcomes of these
      patients, of whom 25 had pKS and 280 did not. RESULTS: Patients with pKS had
      lower CD4 cell counts at the time of KS diagnosis (Mann-Whitney U-test P=0.005).
      The incidence of pKS was higher in African patients than in non-African patients
      in this sample (Fisher's test, P=0.001). There were no significant differences in
      age, gender, plasma HIV-1 viral load or prior HAART treatment at the time of KS
      diagnosis. Five-year overall survival in the pKS group was 49% [95% confidence
      interval (CI) 26-73%] as compared with 82% (95% CI 76-87%) for the non-pKS group
      (log rank, P<0.0001). CONCLUSION: PKS remains an ominous diagnosis in the era of
      HAART, with a median survival of just 1.6 years.

PMID- 16945074
TI  - HIV-1 reverse transcriptase (RT) genotypic patterns and treatment characteristics
      associated with the K65R RT mutation.
AB  - BACKGROUND: The K65R HIV-1 reverse transcriptase (RT) mutation is a multidrug
      resistance mutation which may be correlated with specific antiretroviral
      combinations and with the presence or absence of other RT resistance mutations.
      OBJECTIVES: The aims of this study were: (i) to determine the prevalence of the
      K65R mutation in a cohort of antiretroviral-treated patients; (ii) to study
      genotypic patterns and treatment characteristics in patients in whom the K65R
      mutation was present. STUDY DESIGN: We included in the study all antiretroviral
      experienced patients followed up at the Bordeaux University Hospital in 2003 and
      2004 for whom an HIV-1 genotypic resistance analysis was available. Information
      on RT resistance mutations was reported from a hospital database including
      therapeutic and biological parameters. The prevalence of K65R was investigated
      for all patients. Genotypic patterns and treatment characteristics were examined
      at the time of detection of the K65R mutation. RESULTS: The prevalence of K65R
      was 1.9% (26 of 1404 patients). K65R was associated with nucleoside RT inhibitor
      based regimens in 22 patients, and with tenofovir disoproxil fumarate,
      lamivudine, didanosine and abacavir in 23, 17, 17 and eight patients,
      respectively. The M184V and Q151M mutations were the most commonly co-selected
      substitutions. Thymidine analogue mutations (TAMs) were rarely co-selected with
      K65R and inversely associated with K65R. CONCLUSION: The K65R mutation may emerge
      preferentially in the absence of zidovudine and TAMs, suggesting the possibility
      of an antagonistic interaction between K65 and TAMs.

PMID- 16945075
TI  - Counteracting muscle wasting in HIV-infected individuals.
AB  - HIV-infected persons often experience a loss of lean tissue mass, which includes
      decreases in skeletal muscle mass. This HIV-associated wasting is significant
      because it has been associated with accelerated disease progression and increased
      morbidity. Signalling related to several circulating molecules, including tumour
      necrosis factor (TNF)-alpha, growth hormone, insulin-like growth factor (IGF)-1
      and testosterone, has been associated with the aetiology of muscle wasting.
      Additionally, nutritional status related to malnutrition and specific dietary
      deficiencies may be involved. In an attempt to counter muscle wasting in HIV
      infected persons, treatments have been suggested that target these mechanisms.
      Nutritional supplementation, cytokine reduction, hormone therapy and resistance
      exercise training are potential treatments for this condition. Resistance
      exercise training, which is more easily accessible to this population than other
      treatments, holds promise in counteracting the process of HIV wasting, as it has
      been successfully used to increase lean tissue mass in healthy and clinical
      populations. This review will explore the HIV/AIDS muscle-wasting syndrome, its
      aetiology, and the treatments used to counteract wasting.

PMID- 16945076
TI  - Regimen-dependent variations in adherence to therapy and virological suppression
      in patients initiating protease inhibitor-based highly active antiretroviral
      therapy.
AB  - OBJECTIVE: To examine differences among four protease inhibitor (PI)-based drug
      regimens in adherence to therapy and rate of achievement of virological
      suppression in a cohort of antiretroviral-naive patients initiating highly active
      antiretroviral therapy (HAART). METHODS: Participants were antiretroviral-naive
      and were first dispensed combination therapy containing two nucleosides and a
      ritonavir (RTV)-boosted PI, or unboosted nelfinavir, between 1 January 2000 and
      30 September 2003. Logistic regression analysis was used to examine associations
      between the prescribed PI and other baseline factors associated with being >90%
      adherent to therapy and then to determine the associations of prescribed drug
      regimen, adherence to therapy and baseline variables with the odds of achieving
      two consecutive viral loads of <500 HIV-1 RNA copies/mL. RESULTS A total of 385
      subjects were available for analysis. Lopinavir (LPV)/RTV was prescribed for 168
      patients (42% of total); 86 (22%) received indinavir (IDV)/RTV; 91 (24%) received
      nelfinavir (NFV) and 40 (10%) received saquinavir (SQV)/RTV. SQV/RTV-based HAART
      was associated with reduced adherence to therapy [odds ratio (OR)=0.40; 95%
      confidence interval (CI) 0.19-0.83]. In multivariate models, IDV/RTV (OR=0.45;
      95% CI 0.22-0.92), SQV/RTV (OR=0.18; 95% CI 0.07-0.43) and NFV were associated
      with reduced odds of achieving virological suppression within 1 year in
      comparison to LPV/RTV-based therapy. For patients receiving NFV, adjusting for
      adherence (OR=0.73; 95% CI 0.36-1.47) rendered this association nonsignificant.
      CONCLUSION: Patients prescribed IDV/RTV, NFV or SQV/RTV were less likely to
      achieve virological suppression on their first regimen compared with patients
      prescribed LPV/RTV. Reduced adherence to these therapies only partly explained
      these observed differences.

PMID- 16945078
TI  - The impact of malnutrition on survival and the CD4 count response in HIV-infected
      patients starting antiretroviral therapy.
AB  - BACKGROUND: The impact that malnutrition at the time of starting antiretroviral
      therapy (ART) has on survival and the CD4 count response is not known. METHODS: A
      retrospective cohort study of patients attending the national HIV referral centre
      in Singapore who had a CD4 count less than 250 cells/microL and a measurement of
      body weight performed at the time of starting ART was carried out. Demographic
      and clinical variables were extracted from an existing database. Body mass index
      (BMI) was calculated from the weight in kilograms divided by the square of the
      height in metres. Moderate to severe malnutrition was defined as BMI less than 17
      kg/m(2). Intent-to-treat Cox models were used to determine the predictors of
      survival. RESULTS: A total of 394 patients were included in the analysis, of whom
      79 died during a median study follow-up of 2.4 years. Moderate to severe
      malnutrition was present in 16% of patients at the time of starting ART, and was
      found to be a significant independent predictor of death [hazard ratio (HR) 2.19,
      95% confidence interval (CI) 1.29-3.73, P=0.004 for those with BMI<17 compared
      with those with BMI>18.5] as were stage of disease (HR 2.47, 95% CI 1.20-5.07,
      P=0.014 for those who were at stage C compared with those at stage A) and the
      type of ART [HR 0.50, 95% CI 0.27-0.93, P=0.03 for highly active antiretroviral
      therapy (HAART) compared with non-HAART treatment]. Malnutrition did not impair
      the magnitude of the increase in CD4 count at 6 or 12 months. CONCLUSIONS:
      Malnutrition at the time of starting ART was significantly associated with
      decreased survival, but the effect appeared not to be mediated by impaired immune
      reconstitution. Given the increasing access to ART in developing countries and
      the high frequency of HIV-associated wasting, studies of nutritional therapy as
      an adjunct to the initiation of HAART are urgently needed.

PMID- 16945077
TI  - A prospective evaluation of the effect of atazanavir on the QTc interval and QTc
      dispersion in HIV-positive patients.
AB  - BACKGROUND: Atazanavir (ATV), an HIV protease inhibitor (PI) that may be
      preferred for the treatment of HIV-infected patients with cardiovascular
      comorbidities because of its favourable effects on plasma lipids, has been
      associated with cardiac rhythm disturbances. OBJECTIVE: To quantify the effect of
      ATV on corrected QT (QTc) and QTc dispersion (QTd), markers of the potential for
      cardiac dysrhythmia, in patients switching from other PIs to ATV. METHODS: In
      this prospective, single-centre, open-label study, 12-lead electrocardiograms
      were performed for subjects at baseline, 2 h after the first dose of ATV, and 1
      month after initiation of ATV. RESULTS: Twenty-one patients (19 received
      ritonavir-boosted ATV) completed the study. There was a trend towards an increase
      in the QTc at 2 h after the first dose [mean+/-standard deviation 3.19+/-8.0 ms;
      95% confidence interval (CI) -0.47 to 6.85 ms; P=0.084]. There was no difference
      between QTc values at baseline and at 1 month (-1.5+/-8.75 ms; 95% CI -5.50 to
      2.46; P=0.43). There was a nonsignificant decrease in the QTd between baseline
      and 2 h (-5.1+/-15.19 ms; 95% CI -13.22 to 2.96; P=0.197) and between baseline
      and 1 month (-0.61+/-15.04 ms; 95% CI -8.1 to 6.87; P=0.865). A significant
      increase in the PR interval (7.4+/-10.7 ms; 95% CI 2.5 to 12.25 ms; P=0.005) was
      observed at 1 month. CONCLUSIONS: The use of ATV did not result in increases in
      the QTc interval or QTd. However, PR interval monitoring may be warranted in
      patients with underlying heart block or those treated with atrioventricular nodal
      blocking agents.

PMID- 16945079
TI  - Risk factors for fibrosis progression in HIV/HCV coinfected patients from a
      retrospective analysis of liver biopsies in 1985-2002.
AB  - OBJECTIVES: To identify predictive factors for moderate/severe liver fibrosis and
      to analyse fibrosis progression in paired liver biopsies from HIV-positive
      patients with chronic hepatitis C virus (HCV) infection. METHODS: HIV/HCV
      coinfected patients followed at the 2nd Department of Infectious Diseases of L.
      Sacco Hospital in Milan, Italy, with at least one liver biopsy specimen were
      retrospectively evaluated. RESULTS: A total of 110 patients were enrolled in the
      study. In a univariate analysis, predictive factors of Ishak-Knodell stage > or
      =3 were a history of alcohol abuse [odds ratio (OR) 3.6, P=0.004], alanine
      aminotransferase level >100 IU/L at biopsy (OR 2.4, P=0.05), necro-inflammatory
      grade > or =9 (OR 37.14, P<0.0001) and CD4 count <350 cells/microL at nadir (OR
      5.3, P=0.05). In a multivariate analysis, age >35 years (OR 3.19, P=0.04) and
      alcohol abuse (OR 4.36, P=0.002) remained independently associated with Ishak
      Knodell stage. Paired liver biopsies were available in 36 patients; 18 showed an
      increase of at least one stage in the subsequent liver biopsy. Either in a
      univariate or in a multivariate analysis, a decrease of CD4 cell count of more
      than 10% between two biopsies (OR 6.85, P=0.002) was significantly associated
      with liver fibrosis progression. CONCLUSION: Our findings highlight the relevance
      of encouraging a withdrawal of alcohol consumption in people with chronic HCV
      infection and of carrying out close follow-up of patients, especially if they are
      more than 35 years old. It is therefore mandatory to evaluate HIV/HCV coinfected
      patients for anti-HCV treatment and to increase CD4 cell count through
      antiretroviral therapy in order to reduce the risk of fibrosis progression and to
      slow the evolution of liver disease.

PMID- 16945080
TI  - Safety of nevirapine-containing antiretroviral triple therapy regimens to prevent
      vertical transmission in an African cohort of HIV-1-infected pregnant women.
AB  - OBJECTIVE: To assess the incidence and consequences of adverse reactions among
      African HIV-positive pregnant women treated with fixed-dose combinations of a
      nevirapine-containing antiretroviral (ARV) triple therapy. METHODS: A
      retrospective analysis of the clinical files of 703 HIV-1-positive pregnant women
      treated with a nevirapine-containing regimen between May 2002 and July 2004 was
      conducted. Selection criteria for inclusion in the analysis were: (a) taking ARV
      for more than 14 days; (b) baseline values of transaminases below the threshold
      of 2.5 times the upper limit of normal (ULN). The women were on a nevirapine
      containing regimen for a median of 127 days [interquartile range (IQR) 86-190
      days], starting on average at the 27th week of gestation (standard deviation+/
      9.5) and continuing up to a maximum of 6 months after delivery. All women were
      offered formula milk to feed the babies. Highly active antiretroviral therapy
      (HAART) was continued beyond 6 months only if the patient qualified on the first
      visit. The main outcome measures were incidence of hepatotoxicity, skin rashes
      and Stevens-Johnson syndrome. Multivariate analysis to assess the impact of
      several factors on the adverse reaction rate was performed. RESULTS: As of 1
      August 2004, 554 pregnancies reached term, 96 women were still pregnant, and 53
      women dropped out of the programme before giving birth. After 2 months of therapy
      the percentage of patients with a viral load less than 1000 HIV-1 RNA copies/mL
      increased to 78.6%; average CD4 cell counts increased from 490 cells/microL
      before therapy to 630 after therapy. The incidence of grade 3-4 adverse reactions
      (hepatotoxicity, skin rashes and Stevens-Johnson syndrome) was 6.5, 2.4 and 1.1%,
      respectively. Five women died during pregnancy (0.88%). Only one of the deaths
      could be associated with ARV treatment. CONCLUSION: Nevirapine-containing
      regimens in pregnant woman, at all CD4 cell count levels, appear to be safe in
      African settings.

PMID- 16945082
TI  - Overyielding and stable species coexistence.

PMID- 16945083
TI  - What is the link between carbon and phosphorus fluxes in arbuscular mycorrhizas?
      A null hypothesis for symbiotic function.

PMID- 16945085
TI  - Photoprotection in an ecological context: the remarkable complexity of thermal
      energy dissipation.
AB  - This review places photoprotection into the context of ecology and species
      diversity. The focus is on photoprotection via the safe removal - as thermal
      energy - of excess solar energy absorbed by the light collecting system, which
      counteracts the formation of reactive oxygen species. An update on the
      surprisingly complex, multiple variations of thermal energy dissipation is
      presented, placing these different forms into ecological and genetic contexts.
      Zeaxanthin-facilitated, flexible thermal dissipation associated with the PsbS
      protein and controlled by the trans-thylakoid pH gradient apparently occurs
      ubiquitously in plants, and can become sustained (and thus less flexible) at low
      temperatures. Long-lived, slow-growing plants with low intrinsic capacities for
      photosynthesis have greater capacities for this flexible dissipation than short
      lived, fast-growing species. Furthermore, potent, but inflexible (zeaxanthin
      facilitated) thermal dissipation, prominent in evergreen species under prolonged
      environmental stress, is characterized with respect to the involvement of
      photosystem II core rearrangement and/or degradation as well as the absence of
      control by trans-thylakoid pH and, possibly, PsbS. A role of PsbS-related
      proteins in photoprotection is discussed.

PMID- 16945086
TI  - Isoprenoid metabolism and plastid reorganization in arbuscular mycorrhizal roots.
AB  - Plant root-colonizing arbuscular mycorrhizal (AM) fungi activate the
      methylerythritol phosphate pathway, carotenoid biosynthesis and oxidative
      carotenoid cleavage in roots, leading to C13 and C14 apocarotenoids, that is,
      cyclohexenone and mycorradicin derivatives. Mycorradicin causes the
      characteristic yellow coloration of many AM roots accumulating within a complex
      mixture of unknown components. The accumulating C13 cyclohexenones exhibit
      various ring substitutions and different glycosyl moieties. Transcript levels of
      the first two enzymes of the MEP pathway, 1-deoxy-D-xylulose 5-phosphate synthase
      and 1-deoxy-D-xylulose 5-phosphate reductoisomerase, and of the carotenoid
      pathway, phytoene desaturase and zeta-carotene desaturase, along with a
      carotenoid-cleaving dioxygenase, are markedly increased in AM roots. This
      correlates with proliferation and reorganization of root plastids. These results
      allow at this point only speculation about the significance of apocarotenoid
      accumulation: participation in the production of signaling molecules and control
      of fungal colonization or protection against soil-borne pathogens; protection of
      root cells against oxidative damage of membranes by reactive oxygen species; and
      promotion of the symbiotic interactions between plant roots and AM fungi.

PMID- 16945087
TI  - A journey through signaling in arbuscular mycorrhizal symbioses 2006.
AB  - Recent years have seen fascinating contributions to our understanding of the
      molecular dialogue between fungi and plants entering into arbuscular mycorrhizal
      (AM) symbioses. Attention has shifted from descriptions of physiological and
      cellular events to molecular genetics and modern chemical diagnostics. Genes,
      signal transduction pathways and the chemical structures of components relevant
      to the symbiosis have been defined. This review examines our current knowledge of
      signals and mechanisms involved in the establishment of AM symbioses.

PMID- 16945088
TI  - Genome-wide analysis of the structural genes regulating defense phenylpropanoid
      metabolism in Populus.
AB  - Salicin-based phenolic glycosides, hydroxycinnamate derivatives and flavonoid
      derived condensed tannins comprise up to one-third of Populus leaf dry mass.
      Genes regulating the abundance and chemical diversity of these substances have
      not been comprehensively analysed in tree species exhibiting this metabolically
      demanding level of phenolic metabolism. Here, shikimate-phenylpropanoid pathway
      genes thought to give rise to these phenolic products were annotated from the
      Populus genome, their expression assessed by semiquantitative or quantitative
      reverse transcription polymerase chain reaction (PCR), and metabolic evidence for
      function presented. Unlike Arabidopsis, Populus leaves accumulate an array of
      hydroxycinnamoyl-quinate esters, which is consistent with broadened function of
      the expanded hydroxycinnamoyl-CoA transferase gene family. Greater flavonoid
      pathway diversity is also represented, and flavonoid gene families are larger.
      Consistent with expanded pathway function, most of these genes were upregulated
      during wound-stimulated condensed tannin synthesis in leaves. The suite of
      Populus genes regulating phenylpropanoid product accumulation should have
      important application in managing phenolic carbon pools in relation to climate
      change and global carbon cycling.

PMID- 16945089
TI  - Importance of plant species and external silicon concentration to active silicon
      uptake and transport.
AB  - Here, we characterized silicon (Si) uptake and xylem loading in Oryza sativa, Zea
      mays, Helianthus annuus and Benincase hispida in a series of hydroponic
      experiments. Both active and passive Si-uptake components co-exist in all the
      plants tested. The active component is the major mechanism responsible for Si
      uptake in O. sativa and Z. mays. By contrast, passive uptake prevails in H.
      annuus and B. hispida at a higher external Si concentration (0.85 mM), while the
      active component constantly exists and contributes to the total Si uptake,
      especially at a lower external Si concentration (0.085 mM). Short experiments
      showed that Si uptake was significantly suppressed in O. sativa and Z. mays by
      metabolic inhibitors or low temperature, regardless of external Si
      concentrations. By contrast, Si uptake in H. annuus and B. hispida was inhibited
      more significantly by metabolic inhibitors or low temperature at lower (for
      example, 0.085 mM) than at higher (for example, 1.70 mM) external Si
      concentrations. It can be concluded that both active and passive Si-uptake
      components co-exist in O. sativa, Z. mays, H. annuus and B. hispida, with their
      relative contribution being dependent much upon both plant species and external
      Si concentrations.

PMID- 16945090
TI  - Decreased Rubisco activity during water stress is not induced by decreased
      relative water content but related to conditions of low stomatal conductance and
      chloroplast CO2 concentration.
AB  - Rubisco activity decreases under water stress, for reasons as yet unclear. Here,
      the covariation of stomatal conductance (gs) and relative water content (RWC),
      often observed during water stress, was impaired to assess the separate effects
      of these factors on Rubisco activity. Three different treatments were applied to
      soybean (Glycine max) and tobacco (Nicotiana tabacum): leaf desiccation (LD), in
      which stomatal closure was accompanied by large decreases of RWC; water stress
      (WS), in which minor decreases of RWC were observed along with stomatal closure;
      and exogenous application of abscisic acid (ABA), which triggered stomatal
      closure without changing RWC. Decreased RWC did not induce decreased initial
      Rubisco activity, which was impaired only in soybean by 40% when the gs dropped
      below 50 mmol m(-2) s(-1), regardless of the treatment. The mechanism for
      decreased activity differed among treatments, owing to decreased activation in LD
      and to total activity and protein content in WS and ABA. Despite the occurrence
      of Rubisco regulation, CO2 availability in the chloroplast, not impairment of
      Rubisco activity, limits photosynthesis during WS.

PMID- 16945091
TI  - Growth towards light as an adaptation to high light conditions in Chara branches.
AB  - Growth of plants or plant organs towards more light is commonly interpreted as an
      adaptation to low light conditions. Here, we show for the first time, in a study
      of charophyte branches, a growth-based orientation towards light functioning as a
      mechanism to protect the plant from excessive light. Two Chara species were
      exposed to five different intensities of photosynthetically active radiation and
      species traits and pigmentation were measured. Branches of plants exposed to
      higher light intensities were convergent and pointed steeply upwards, whereas
      those exposed to lower light intensities grew nearly straight and were less
      inclined. Only branches that increased in length during the experiments reacted
      to differences in light intensity. This indicates that branch orientation is
      determined by a light-dependent growth reaction. Orientation of charophyte
      branches towards light is accompanied by a decrease in chlorophyll a (Chla)
      content and a lower Chla : carotenoid ratio, which clearly indicates that the
      plant is taking protective measures against potentially damaging excess light
      conditions. We suggest that the growth-based orientation of Chara branches
      towards light may protect sexual organs, which grow on adaxial branch sides, from
      light damage. In addition, the upward orientation of branches might lead to
      increased light transmission within dense charophyte beds, thus enabling an
      enhanced gross production.

PMID- 16945092
TI  - Elevated CO2 induces physiological, biochemical and structural changes in leaves
      of Arabidopsis thaliana.
AB  - Leaves of Arabidopsis thaliana grown under elevated or ambient CO2 (700 or 370
      micromol mol(-1), respectively) were examined for physiological, biochemical and
      structural changes. Stomatal characters, carbohydrate and mineral nutrient
      concentrations, leaf ultrastructure and plant hormone content were investigated
      using atomic absorption spectrophotometry, transmission electron microscopy and
      enzyme-linked immunosorbent assay (ELISA). Elevated CO2 reduced the stomatal
      density and stomatal index of leaves, and also reduced stomatal conductance and
      transpiration rate. Elevated CO2 increased chloroplast number, width and profile
      area, and starch grain size and number, but reduced the number of grana thylakoid
      membranes. Under elevated CO2, the concentrations of carbohydrates and plant
      hormones, with the exception of abscisic acid, increased whereas mineral nutrient
      concentrations declined. These results suggest that the changes in chloroplast
      ultrastructure may primarily be a consequence of increased starch accumulation.
      Accelerated A. thaliana growth and development in elevated CO2 could in part be
      attributed to increased foliar concentrations of plant hormones. The reductions
      in mineral nutrient concentrations may be a result of dilution by increased
      concentrations of carbohydrates and also of decreases in stomatal conductance and
      transpiration rate.

PMID- 16945093
TI  - Leaf lifespan and lifetime carbon balance of individual leaves in a stand of an
      annual herb, Xanthium canadense.
AB  - Leaf lifespan in response to resource availability has been documented in many
      studies, but it still remains uncertain what determines the timing of leaf
      shedding. Here, we evaluate the lifetime carbon (C) balance of a leaf in a canopy
      as influenced by nitrogen (N) availability. Stands of Xanthium canadense were
      established with high-nitrogen (HN) and low-nitrogen (LN) treatments and temporal
      changes of C gain of individual leaves were investigated with a canopy
      photosynthesis model. Daily C gain of a leaf was maximal early in its development
      and subsequently declined. Daily C gain at shedding was nearly zero in HN, while
      it was still positive in LN. Sensitivity analyses showed that the decline in the
      daily C gain resulted primarily from the reduction in light level in HN and by
      the reduction in leaf N in LN. Smaller leaf size in LN than in HN led to higher
      light levels in the canopy, which helped leaves of the LN stand maintain for a
      longer period. These results suggest that the mechanism by which leaf lifespan is
      determined changes depending on the availability of the resource that is most
      limiting to plant growth.

PMID- 16945094
TI  - An overlooked carbon source for grassland soils: loss of structural carbon from
      stubble in response to elevated pCO2 and nitrogen supply.
AB  - In grasslands, the loss of structural carbon (C) from nonharvested plant parts is
      a primary C source for the soil. The amount of input depends not only on the size
      of structural C pools but also on their loss rates. In the field, we examined the
      effects of elevated atmospheric partial pressures of CO2 (pCO2) and nitrogen (N)
      supply on pool size and rates of structural C loss in stubble and roots of
      perennial ryegrass (Lolium perenne) by using multiple-pulse labelling and steady
      state labelling. Stubble retained structural C for roughly half the time it was
      retained in roots. Elevated pCO2 combined with low N supply enlarged the pools of
      roots and stubble. These conditions also stimulated the rate of structural C loss
      from stubble and, thus, the amounts available for further transformation. The
      potential of multiple-pulse labelling as a field technique is highlighted. The
      stimulation of structural C loss from stubble by elevated pCO2 at low N provides
      a missing link between increased C assimilation and low yield response and
      indicates a potentially higher input of structural C into the soil.

PMID- 16945095
TI  - Relating geographical variation in pollination types to environmental and spatial
      factors using novel statistical methods.
AB  - The relative frequencies of functional traits of plant species show notable
      spatial variation, which is often related to environmental factors. Pollination
      type (insect-, wind- or self-pollination) is a critical trait for plant
      reproduction and provision of ecosystem services. Here, we mapped the
      distribution of pollination types across Germany by combining databases on plant
      distribution and plant pollination types. Applying a new method, we modelled the
      composition of pollination types using a set of 12 environmental variables as
      predictors within a Bayesian framework which allows for the analysis of
      compositional data in the presence of spatial autocorrelation. A clear
      biogeographical pattern in the distribution of pollination types was revealed
      which was adequately captured by our model. The most striking relationship was a
      relative increase in insect-pollination and a corresponding decrease of selfing
      with increasing altitude. Further important factors were wind speed, geology and
      land use. We present a powerful tool to analyse the distribution patterns of
      plant functional types such as pollination types and their relationship with
      environmental parameters in a spatially explicit framework.

PMID- 16945096
TI  - Overyielding and species diversity: what should we expect?
AB  - Recent empirical studies have found evidence of increased biomass production
      ('overyielding') in species mixtures relative to monoculture, but the
      interpretation of these results remains controversial, in part, because of the
      lack of a theoretical expectation. Here, we examined the expected frequency and
      stability of overyielding species mixtures using Lotka-Volterra models of species
      dynamics in two- and four-species systems in conjunction with community,
      population, and specific rate of biomass production (SRP) definitions of
      overyielding. Overyielding plant mixtures represented > 55% of potential species
      assemblages under community definitions and approximately 100% of species were
      either overyielding or underyielding under the population definition. Our species
      simulations approached their equilibria in 1-2 yr, supporting the relevancy of an
      equilibrial analysis. The range of parameter space that we explored produced
      realistic values of plot biomass, supporting their biological relevance. We show
      that overyielding is expected to be common under community definitions and
      population definitions. Overyielding, under community or population definitions,
      does not imply an actual increase in the specific rate of biomass production. In
      addition, assemblages of overyielding and underyielding species under all three
      definitions can be stable over time with underyielding species persisting in the
      presence of overyielding species.

PMID- 16945097
TI  - Influence of long-term repeated prescribed burning on mycelial communities of
      ectomycorrhizal fungi.
AB  - To demonstrate the efficacy of direct DNA extraction from hyphal ingrowth bags
      for community profiling of ectomycorrhizal (ECM) mycelia in soil, we applied the
      method to investigate the influence of long-term repeated prescribed burning on
      an ECM fungal community. DNA was extracted from hyphal ingrowth bags buried in
      forest plots that received different prescribed burning treatments for 30 yr, and
      denaturing gradient gel electrophoresis (DGGE) profiles of partial fungal rDNA
      internal transcribed spacer (ITS) regions were compared. Restriction fragment
      length polymorphism (RFLP) and sequence analyses were also used to compare clone
      assemblages between the treatments. The majority of sequences derived from the
      ingrowth bags were apparently those of ECM fungi. DGGE profiles for biennially
      burned plots were significantly different from those of quadrennially burned and
      unburned control plots. Analysis of clone assemblages indicated that this
      reflected altered ECM fungal community composition. The results indicate that
      hyphal ingrowth bags represent a useful method for investigation of ECM mycelial
      communities, and that frequent long-term prescribed burning can influence below
      ground ECM fungal communities.

PMID- 16945098
TI  - Molecular analysis of arbuscular mycorrhizal fungi colonising a semi-natural
      grassland along a fertilisation gradient.
AB  - The community of arbuscular mycorrhizal fungi (AMF) colonizing the roots of
      Festuca pratensis and Achillea millefolium was characterized in a Swedish pasture
      at different times, along a gradient of fertilization. The small subunit
      ribosomal RNA gene was subjected to PCR and denaturing gradient gel
      electrophoresis (DGGE), sequencing and phylogenetic analysis. The sequences found
      in this study clustered in 10 discrete sequence groups, seven belonging to
      Glomus, two to Scutellospora and one to Diversispora. A negative correlation was
      observed between soil mineral nitrogen and the number of AMF sequence groups in
      the roots. The frequency of occurrence of AMF in roots decreased dramatically
      between June and September. No plant-host specificity could be detected.

PMID- 16945099
TI  - Long-distance dispersal vs vicariance: the origin and genetic diversity of alpine
      plants in the Spanish Sierra Nevada.
AB  - Here, we investigated the origin and genetic diversity of four alpine plant
      species co-occurring in the Spanish Sierra Nevada and other high mountains in
      south-western Europe by analysis of amplified fragment length polymorphisms
      (AFLPs). In Kernera saxatilis, Silene rupestris and Gentiana alpina we found
      intraspecific phylogroups corresponding to mountain regions as predicted by the
      vicariance hypothesis. Moreover, genetic distances between Sierra Nevada and
      Pyrenees populations were always higher than those between populations from the
      Pyrenees and the south-western Alps/Massif Central. This suggests successive
      disruption of gene exchange between mountain ranges as postglacial climatic
      warming proceeded from south to north. In Papaver alpinum, our data indicate that
      a central Pyrenean population arose via long-distance dispersal from the Sierra
      Nevada, and that vicariant separation events between the Sierra Nevada and the
      Pyrenees and between the Pyrenees and the south-western Alps occurred
      simultaneously. Overall, Sierra Nevada populations of all species investigated
      here preserve unexpectedly high (or not exceptionally reduced) genetic diversity.
      This testifies to the important influence of long-term isolation, i.e.
      vicariance, on genetic diversity through fostering the accumulation of new
      mutations and/or the fixation of ancestral ones.

PMID- 16945100
TI  - Pin1 in Alzheimer's disease.
AB  - Proteolytic processing and phosphorylation of amyloid precursor protein (APP),
      and hyperphosphorylation of tau protein, have been shown to be increased in
      Alzheimer's disease (AD) brains, leading to increased production of beta-amyloid
      (Abeta) peptides and neurofibrillary tangles, respectively. These observations
      suggest that phosphorylation events are critical to the understanding of the
      pathogenesis and treatment of this devastating disease. Pin-1, one of the
      peptidyl-prolyl isomerases (PPIase), catalyzes the isomerization of the peptide
      bond between pSer/Thr-Pro in proteins, thereby regulating their biological
      functions which include protein assembly, folding, intracellular transport,
      intracellular signaling, transcription, cell cycle progression and apoptosis. A
      number of previous studies have shown that Pin1 is co-localized with
      phosphorylated tau in AD brain, and shows an inverse relationship to the
      expression of tau. Pin1 protects neurons under in vitro conditions. Moreover,
      recent studies demonstrate that APP is a target for Pin1 and thus, in Abeta
      production. Furthermore, Pin1 was found to be oxidatively modified and to have
      reduced activity in the hippocampus in mild cognitive impairment (MCI) and AD.
      Because of the diverse functions of Pin1, and the discovery that this protein is
      one of the oxidized proteins common to both MCI and AD brain, the question arises
      as to whether Pin1 is one of the driving forces for the initiation or progression
      of AD pathogenesis, finally leading to neurodegeneration and neuronal apoptosis.
      In the present review, we discuss the role of Pin1 with respect to Alzheimer's
      disease.

PMID- 16945101
TI  - Developmental expression of the SRF co-activator MAL in brain: role in regulating
      dendritic morphology.
AB  - The dynamic changes in dendritic morphology displayed by developing and mature
      neurons have stimulated interest in deciphering the signaling pathways involved.
      Recent studies have identified megakaryocytic acute leukemia (MAL), a serum
      response factor (SRF) co-activator, as a key component of a signaling pathway
      linking changes in the actin cytoskeleton to SRF-mediated transcription. To help
      define the role of this pathway in regulating dendritic morphology, we have
      characterized the pattern of MAL expression in the developing and adult brain,
      and have examined its role in regulating dendritic morphology in cultured
      cortical neurons. In histological studies of mouse brain, we found prominent
      expression of MAL in neurons in adult hippocampus and cerebral cortex. MAL
      immunostaining revealed localization of this protein in neuronal cell bodies and
      apical dendrites. During development, an increase in MAL expression occurs during
      the second post-natal week. Expression of dominant negative MAL constructs or MAL
      siRNA in cortical neurons grown in primary culture reduces the number of
      dendritic processes and decreases the basal level of SRF-mediated transcription.
      Taken together, these findings indicate that the MAL-SRF signaling pathway plays
      a key role in regulating dendritic morphology.

PMID- 16945102
TI  - SNAP25 is a pre-synaptic target for the depressant action of reactive oxygen
      species on transmitter release.
AB  - Reactive oxygen species (ROS) participate in various physiological and
      pathological processes in the nervous system, but the specific pathways that
      mediate ROS signalling remain largely unknown. Using electrophysiological
      techniques and biochemical evaluation of isolated fusion proteins, we explored
      the sensitivity to standard oxidative stress of the entire synapse, the pre
      synaptic machinery and essential fusion proteins underlying transmitter
      exocytosis. Oxidative stress induced by H(2)O(2) plus Fe(2+) inhibited both
      evoked and spontaneous quantal release from frog or mouse motor nerve endings,
      while it left post-synaptic sensitivity unchanged. The depressant effect of
      H(2)O(2) on acetylcholine release was pertussis toxin-insensitive, ruling out G
      protein cascades. Experiments with ionomycin, a Ca(2+) ionophore, revealed that
      ROS directly impaired the function of releasing machinery. In line with this,
      SNAP25, one of three essential fusion proteins, showed a selectively high
      sensitivity to the oxidative signals. Several ROS scavengers enhanced evoked
      synaptic transmission, consistent with tonic inhibition by endogenous ROS. Our
      data suggest that ROS-induced impairment of releasing machinery is mediated by
      SNAP25, which appears to be a pre-synaptic ROS sensor. This mechanism of ROS
      signalling could have widespread implications in the nervous system and might
      contribute to the pathogenesis of neurodegenerative diseases.

PMID- 16945103
TI  - The transcriptional repressor REST is a critical regulator of the neurosecretory
      phenotype.
AB  - Release of distinct cellular cargoes in response to specific stimuli is a process
      fundamental to all higher eukaryotes and controlled by the regulated secretory
      pathway (RSP). However, the mechanism by which genes involved in the RSP are
      selectively expressed, leading to the establishment and appropriate functioning
      of regulated secretion remaining largely unknown. Using the rat pheochromocytoma
      cell line PC12, we provide evidence that, by controlling expression of many genes
      involved in the RSP, the transcriptional repressor REST can regulate this pathway
      and hence the neurosecretory phenotype. Introduction of REST transgenes into PC12
      cells leads to the repression of many genes, the products of which are involved
      in regulated secretion. Moreover, chromatin immunoprecipitation assays show that
      many of the repressed genes recruit the recombinant REST protein to RE1 sites
      within their promoters and abrogation of REST function leads to reactivation of
      these transcripts. In addition to the observed transcriptional effects, PC12
      cells expressing REST have fewer secretory granules and a reduction in the
      ability to store and release noradrenaline. Furthermore, an important trigger for
      synaptic release, influx of calcium through voltage-operated calcium channels, is
      compromised. This is the first demonstration of a transcription factor that
      directly controls expression of many major components of the RSP and provides
      further insight into the function of REST.

PMID- 16945104
TI  - Neuronal sensitivity to kainic acid is dependent on the Nrf2-mediated actions of
      the antioxidant response element.
AB  - The transcription factor, nuclear factor E2 (erythroid-derived 2)-related factor
      2 (Nrf2), is essential for the induction of a battery of phase II detoxification
      genes through the antioxidant response element (ARE) that lies in their promoter
      region. Genes driven by the ARE are up-regulated in response to various stressors
      of the cellular environment. These genetic changes to the cellular reducing
      potential may reflect an intrinsic damage response to harmful toxicants. Analysis
      of transgenic reporter mice following kainate injection revealed selective ARE
      activation within the damaged hippocampus. Further, 2 x 2 microarray analyses
      comparing Nrf2 knockout versus wild-type hippocampi unmasked gene changes
      associated with ion movement and myelination, in addition to alterations to
      detoxification-related genes. Nrf2 knockout mice were more sensitive to kainate
      toxicity, as evidenced by elevated seizure severity, seizure duration,
      hippocampal neuron damage and mortality. Knockout mice injected with kainate
      displayed altered glial fibrillary acidic protein immunoreactivity and increased
      microglial infiltration. The wild-type to knockout damage differential was not
      dependent on the peripheral metabolism of the excitotoxin, was well correlated
      with increased seizure susceptibility, and was therefore not necessarily the
      neuroprotective effects of Nrf2. These results combine to support a role for Nrf2
      in the neural cell defense response of the adult brain.

PMID- 16945105
TI  - Loss of the cellular prion protein affects the Ca2+ homeostasis in hippocampal
      CA1 neurons.
AB  - Previous neurophysiological studies on prion protein deficient (Prnp(-/-)) mice
      have revealed a significant reduction of slow afterhyperpolarization currents
      (sI(AHP)) in hippocampal CA1 pyramidal cells. Here we aim to determine whether
      loss of PrP(C.) directly affects the potassium channels underlying sI(AHP) or if
      sI(AHP) is indirectly disturbed by altered intracellular Ca(2+) fluxes. Patch
      clamp measurements and confocal Ca(2+) imaging in acute hippocampal slice
      preparations of Prnp(-/-) mice compared to littermate control mice revealed a
      reduced Ca(2+) rise in CA1 neurons lacking PrP(C) following a depolarization
      protocol known to induce sI(AHP). Moreover, we observed a reduced Ca(2+) influx
      via l-type voltage gated calcium channels (VGCCs). No differences were observed
      in the protein expression of the pore forming alpha1 subunit of VGCCs Prnp(-/-)
      mice. Surprisingly, the beta2 subunit, critically involved in the transport of
      the alpha1 subunit to the plasma membrane, was found to be up-regulated in knock
      out hippocampal tissue. On mRNA level however, no differences could be detected
      for the alpha1C, D and beta2-4 subunits. In conclusion our data support the
      notion that lack of PrP(C.) does not directly affect the potassium channels
      underlying sI(AHP), but modulates these channels due to its effect on the
      intracellular free Ca(2+) concentration via a reduced Ca(2+) influx through l
      type VGCCs.

PMID- 16945106
TI  - Changes in cerebral membrane lipid composition and fluidity during thioacetamide
      induced hepatic encephalopathy.
AB  - Lipids are an essential structural and functional component of cellular
      membranes. Changes in membrane lipid composition are known to affect the
      activities of many membrane-associated enzymes, endocytosis, exocytosis, membrane
      fusion and neurotransmitter uptake, and have been implicated in the
      pathophysiology of many neurodegenerative disorders. In the present study, we
      investigated changes in the lipid composition of membranes isolated from the
      cerebral cortex of rats treated with thioacetamide (TAA), a hepatotoxin that
      induces fulminant hepatic failure (FHF) and thereon hepatic encephalopathy (HE).
      HE refers to acute neuropsychiatric changes accompanying FHF. The estimation of
      membrane phospholipids, cholesterol and fatty acid content in cerebral cortex
      membranes from TAA-treated rats revealed a decrease in cholesterol,
      phosphatidylserine, sphingomyelin, a monounsaturated fatty acid, namely oleic
      acid, and the polyunsaturated fatty acids gamma-linolenic acid, decosa hexanoic
      acid and arachidonic acid compared with controls. Assessment of membrane fluidity
      with pyrene, 1,6-diphenyl-1,3,5-hexatriene and 1-[4-(trimethylammonio)phenyl]-6
      phenyl-1,3,5-hexatriene revealed a decrease in the annular membrane fluidity,
      whereas the global fluidity was unaffected. The level of the thiobarbituric acid
      reactive species marker for lipid peroxidation also increased in membranes from
      TAA-treated rats, thereby indicating the prevalence of oxidative stress. Results
      from the present study demonstrate gross alterations in cerebral cortical
      membrane lipid composition and fluidity during TAA-induced HE, and their possible
      implications in the pathogenesis of this condition are also discussed.

PMID- 16945107
TI  - The hereditary spastic paraplegia protein spartin localises to mitochondria.
AB  - Hereditary spastic paraplegia describes a diverse group of disorders
      characterized by progressive paraparesis primarily affecting lower limbs. In
      Troyer syndrome, an autosomal recessive form of hereditary spastic paraplegia,
      patients have dysarthria, distal amyotrophy, developmental delay and short
      stature in addition to spastic paraparesis. It is caused by a frameshift mutation
      (1110delA) in SPG20 leading to premature truncation of spartin, a protein with no
      known function. The objective of this study was to determine the subcellular
      localization of spartin and investigate the effect of the 1110delA mutation. We
      observed cytoplasmic expression of spartin in all transfected cell lines. Using
      superimposed organelle markers or immunocytochemistry staining, we established
      that spartin localizes to mitochondria and that this localization is dependent on
      sequences in the C-terminal region. Mutant spartin containing the 1110delA
      mutation has lost mitochondrial localization. Immunocytochemistry staining using
      anti-alpha-tubulin antibody provided evidence for partial co-localization of
      spartin with microtubules. Analysis of fluorescence resonance energy transfer
      indicated that sequences in the amino terminal are important in mediating
      microtubule interaction. This study provides the first evidence of spartin
      subcellular localization and identifies it as the third mitochondrial protein
      implicated in hereditary spastic paraplegia. Our results suggest that Troyer
      syndrome may be due to defective microtubule-mediated trafficking of mitochondria
      and/or mitochondrial dysfunction.

PMID- 16945108
TI  - Protean agonism of the lysophosphatidic acid receptor-1 with Ki16425 reduces
      nerve growth factor-induced neurite outgrowth in pheochromocytoma 12 cells.
AB  - We report here a novel role for the constitutively active lysophosphatidic acid
      receptor-1 (LPA(1)) receptor in providing Gbetagamma subunits for use by the Trk
      A receptor. This enhances the ability of nerve growth factor (NGF) to promote
      signalling and cell response. These conclusions were based on three lines of
      evidence. Firstly, the LPA(1) receptor was co-immunoprecipitated with the Trk A
      receptor from lysates, suggesting that these proteins form a complex. Secondly,
      Ki16425, a selective protean agonist of the LPA(1) receptor, decreased
      constitutive basal and LPA-induced LPA(1) receptor-stimulated GTPgammaS binding.
      Ki16425 reduced the LPA-induced activation of p42/p44 mitogen activated protein
      kinase (MAPK), while acting as a weak stimulator of p42/p44 MAPK on its own,
      properties typical of a protean agonist. Significantly, Ki16425 also reduced the
      NGF-induced stimulation of p42/p44 MAPK and inhibited NGF-stimulated neurite
      outgrowth. Thirdly, the over-expression of the C-terminal GRK-2 peptide, which
      sequesters Gbetagamma subunits, reduced the NGF-induced activation of p42/p44
      MAPK. In contrast, the stimulation of PC12 cells with LPA leads to a predominant
      G(i)alpha2-mediated Trk A-independent activation of p42/p44 MAPK, where
      Gbetagamma subunits play a diminished role. These findings suggest a novel role
      for the constitutively active LPA(1) receptor in regulating NGF-induced neuronal
      differentiation.

PMID- 16945109
TI  - Toxicity mediated by soluble oligomers of beta-amyloid(1-42) on cholinergic
      SN56.B5.G4 cells.
AB  - Alzheimer's disease (AD) is characterized by cholinergic dysfunction and
      progressive basal forebrain cell loss which has been assumed to be as a result of
      the extensive accumulation of beta-amyloid (Abeta). In addition to Abeta
      fibrillar assemblies, there are pre-fibrillar forms that have been shown to be
      neurotoxic, although their role in cholinergic degeneration is still not known.
      Using the cholinergic cell line SN56.B5.G4, we investigated the effect of
      different Abeta(1-42) aggregates on cell viability. In our model, only soluble
      oligomeric but not fibrillar Abeta(1-42) forms induced toxicity in cholinergic
      cells. To determine whether the neurotoxicity of oligomeric Abeta(1-42) was
      caused by its oxidative potential, we performed microarray analysis of SN56.B5.G4
      cells treated either with oligomeric Abeta(1-42) or H(2)O(2). We showed that
      genes affected by Abeta(1-42) differed from those affected by non-specific
      oxidative stress. Many of the genes affected by Abeta(1-42) were present in the
      endoplasmic reticulum (ER), Golgi apparatus and/or otherwise involved in protein
      modification and degradation (chaperones, ATF6), indicating a possible role for
      ER-mediated stress in Abeta-mediated toxicity. Moreover, a number of genes, which
      are known to be involved in AD (clusterin, Slc18a3), were identified. This study
      provides important leads for the understanding of oligomeric Abeta(1-42) toxicity
      in cholinergic cells, which may account in part for cholinergic degeneration in
      AD.

PMID- 16945110
TI  - Am5-HT7: molecular and pharmacological characterization of the first serotonin
      receptor of the honeybee (Apis mellifera).
AB  - The biogenic amine serotonin (5-HT) plays a key role in the regulation and
      modulation of many physiological and behavioural processes in both vertebrates
      and invertebrates. These functions are mediated through the binding of serotonin
      to its receptors, of which 13 subtypes have been characterized in vertebrates. We
      have isolated a cDNA from the honeybee Apis mellifera (Am5-ht7) sharing high
      similarity to members of the 5-HT(7) receptor family. Expression of the Am5-HT(7)
      receptor in HEK293 cells results in an increase in basal cAMP levels, suggesting
      that Am5-HT(7) is expressed as a constitutively active receptor. Serotonin
      application to Am5-ht7-transfected cells elevates cyclic adenosine 3',5'
      monophosphate (cAMP) levels in a dose-dependent manner (EC(50) = 1.1-1.8 nm). The
      Am5-HT(7) receptor is also activated by 5-carboxamidotryptamine, whereas
      methiothepin acts as an inverse agonist. Receptor expression has been
      investigated by RT-PCR, in situ hybridization, and western blotting experiments.
      Receptor mRNA is expressed in the perikarya of various brain neuropils, including
      intrinsic mushroom body neurons, and in peripheral organs. This study marks the
      first comprehensive characterization of a serotonin receptor in the honeybee and
      should facilitate further analysis of the role(s) of the receptor in mediating
      the various central and peripheral effects of 5-HT.

PMID- 16945111
TI  - Defective processing of neuropeptide precursors in Caenorhabditis elegans lacking
      proprotein convertase 2 (KPC-2/EGL-3): mutant analysis by mass spectrometry.
AB  - Biologically active peptides are synthesized as larger inactive proprotein
      peptide precursors which are processed by the concerted action of a cascade of
      enzymes. Among the proprotein convertases, PC2 is widely expressed in neuro
      endocrine tissues and has been proposed to be the major convertase involved in
      the biosynthesis of neuropeptides. In this study, we have examined the role of
      the Caenorhabditis elegans orthologue PC2/EGL-3 in the processing of proprotein
      peptide precursors. We recently isolated and identified 60 endogenous peptides in
      the nematode C. elegans by two-dimensional nanoscale liquid chromatography -
      quadrupole time-of-flight tandem mass spectrometry. In the present study, we
      compare the peptide profile of different C. elegans strains, including PC2/EGL-3
      mutants. For this purpose, we used an offline approach in which HPLC fractions
      are analysed by a matrix-assisted laser desorption ionisation - time of flight
      mass spectrometer. This differential peptidomic approach unambiguously provides
      evidence for the role of PC2/EGL-3 in the processing of FMRFamide-like peptide
      (FLP) precursors and neuropeptide-like protein (NLP) precursors in nematodes.

PMID- 16945112
TI  - Nerve growth factor-induced phosphorylation of amphiphysin-1 by casein kinase 2
      regulates clathrin-amphiphysin interactions.
AB  - Amphiphysins interact directly with clathrin and have a function in clathrin
      mediated synaptic vesicle recycling and clathrin-mediated endocytosis. The
      neuronal isoform amphiphysin-1 is a serine/threonine phosphoprotein that is
      dephosphorylated upon stimulation of synaptic vesicle endocytosis.
      Rephosphorylation was stimulated by nerve growth factor. We analysed the
      regulation of amphiphysin-clathrin interactions by phosphorylation. The N
      terminal domain of clathrin bound to unphosphorylated amphiphysin-1, but not to
      the phosphorylated protein. A search for possible phosphorylation sites revealed
      two casein kinase 2 consensus motifs in close proximity to the clathrin binding
      sites in amphiphysin-1 and -2. We mutagenized these residues (T350 and T387) to
      glutamate, mimicking a constitutive phosphorylation. The double mutant showed a
      strong reduction in clathrin binding. The assumption that casein kinase 2
      phosphorylates amphiphysin-1 at T350 and T387 was corroborated by experiments
      showing that: (i) casein kinase 2 phosphorylated these residues directly in
      vitro, (ii) when expressed in HeLa cells, the glutamate mutant showed reduced
      phosphorylation, and (iii) casein kinase 2 inhibitors blocked nerve growth factor
      induced phosphorylation of endogenous amphiphysin-1 in PC12 cells. These
      observations are consistent with the hypothesis that, upon activation by nerve
      growth factor, casein kinase 2 phosphorylates amphiphysin-1 and thereby regulates
      the endocytosis of clathrin-coated vesicles via the interaction between clathrin
      and amphiphysin.

PMID- 16945113
TI  - Inhibition of neuronal nitric oxide synthase activity by N1-acetyl-5
      methoxykynuramine, a brain metabolite of melatonin.
AB  - We assessed the effects of melatonin, N(1)-acetyl-N (2)-formyl-5
      methoxykynuramine (AFMK) and N(1)-acetyl-5-methoxykynuramine (AMK) on neuronal
      nitric oxide synthase (nNOS) activity in vitro and in rat striatum in vivo.
      Melatonin and AMK (10(-11)-10(-3) m), but not AFMK, inhibited nNOS activity in
      vitro in a dose-response manner. The IC(50) value for AMK (70 microm) was
      significantly lower than for melatonin (>1 mm). A 20% nNOS inhibition was reached
      with either 10(-9) m melatonin or 10(-11) m AMK. AMK inhibits nNOS by a non
      competitive mechanism through its binding to Ca(2+)-calmodulin (CaCaM). The
      inhibition of nNOS elicited by melatonin, but not by AMK, was blocked with 0.05
      mm norharmane, an indoleamine-2,3-dioxygenase inhibitor. In vivo, the potency of
      AMK to inhibit nNOS activity was higher than that of melatonin, as a 25%
      reduction in rat striatal nNOS activity was found after the administration of
      either 10 mg/kg of AMK or 20 mg/kg of melatonin. Also, in vivo, the
      administration of norharmane blocked the inhibition of nNOS produced by melatonin
      administration, but not the inhibition produced by AMK. These data reveal that
      AMK rather than melatonin is the active metabolite against nNOS, which may be
      inhibited by physiological levels of AMK in the rat striatum.

PMID- 16945114
TI  - Regulation of N-acetylaspartate and N-acetylaspartylglutamate biosynthesis by
      protein kinase activators.
AB  - The neuronal dipeptide N-acetylaspartylglutamate (NAAG) is thought to be
      synthesized enzymatically from N-acetylaspartate (NAA) and glutamate. We used
      radiolabeled precursors to examine NAA and NAAG biosynthesis in SH-SY5Y human
      neuroblastoma cells stimulated with activators of protein kinase A (dbcAMP; N6,2'
      O-dibutyryl cAMP) and protein kinase C (PMA; phorbol-12-myristate-13-acetate).
      Differentiation over the course of several days with dbcAMP resulted in increased
      endogenous NAA levels and NAAG synthesis from l-[(3)H]glutamine, whereas PMA
      induced differentiation reduced both. Exogenously applied NAA caused dose
      dependent increases in intracellular NAA levels, and NAAG biosynthesis from l
      [(3)H]glutamine, suggesting precursor-product and mass-action relationships
      between NAA and NAAG. Incorporation of l-[(3)H]aspartate into NAA and NAAG
      occurred sequentially, appearing in NAA by 1 h, but not in NAAG until between 6
      and 24 h. Synthesis of NAAG from l-[(3)H]aspartate was increased by dbcAMP and
      decreased by PMA at 24 h. The effects of PMA on l-[(3)H]aspartate incorporation
      into NAA were temporally biphasic. Using short incubation times (1 and 6 h), PMA
      increased l-[(3)H]aspartate incorporation into NAA, but with longer incubation
      (24 h), incorporation was significantly reduced. These results suggest that,
      while the neuronal production of NAA and NAAG are biochemically related,
      significant differences exist in the regulatory mechanisms controlling their
      biosynthesis.

PMID- 16945116
TI  - Population pharmacokinetics of darbepoetin alfa in haemodialysis and peritoneal
      dialysis patients after intravenous administration.
AB  - AIMS: To characterize the pharmacokinetics of darbepoetin alfa and covariate
      relationships in haemodialysis (HD) and peritoneal dialysis (PD) patients.
      METHODS: Data were collected from 131 (63 HD and 68 PD) patients who received
      darbepoetin alfa intravenously. A total of 917 serum concentrations were
      available. The data were analysed by nonlinear mixed effect modelling using
      NONMEM with a model including endogenous erythropoietin production. In addition,
      the final model was evaluated using bootstrap resampling. RESULTS: The selected
      basic model was a two-compartment model with a combination of additive and the
      constant coefficient of variation error models. The significant covariates were
      weight (WT) for clearance (CL) and the volume of central compartment (V(1)), and
      the dialysis technique (DIA) for V(1). The typical values of CL and V(1) were
      0.0807 l h(-1) and 2.51 l, respectively. V(1) in PD patients was 17% higher than
      in HD patients. With the introduction of WT in CL and WT and DIA in V(1),
      interindividual variability decreased from 27.1% to 20.6% in CL and from 29.1% to
      21.8% in V(1). The mean parameter estimates from the bootstrap datasets were
      similar to those from the original dataset. Evaluation by bootstrapping showed
      that the final model was stable. CONCLUSIONS: The results of the present analysis
      suggest no dosage regimen change is warranted for darbepoetin alfa in HD and PD
      patients over the range of distribution of covariates included in this study.

PMID- 16945117
TI  - Obesity among female adolescents in Vienna, Austria--the impact of childhood
      weight status and ethnicity.
AB  - OBJECTIVE: The objective of the study was to analyse prevalence of overweight and
      obesity among migrant girls in Vienna, Austria, starting at the age of 6 years up
      to the age of 15 years. DESIGN: In a longitudinal study, the prevalence of
      overweight and obesity among migrant girls from Turkey and former Yugoslavia was
      documented and compared with that among Austrian girls in Vienna. SETTING:
      Medical investigation of medical school authority in Viennese schools. SAMPLE:
      Seven hundred and ninety girls of low socio-economic status were included in the
      study. METHODS: Anthropometric data were collected at the age of 6, 10 and 15
      years. Body mass was estimated by means of the body mass index (BMI), and
      percentile curves were used for determining the weight status. MAIN OUTCOME
      MEASURE: Stature, body weight, BMI, weight status. RESULTS: The prevalence of
      overweight and obesity was significantly higher among migrant girls at all age
      groups. The highest percentage of overweight was found among 10-year-old girls
      from Yugoslavia (nearly 35%) and the lowest percentage of overweight was
      exhibited in 6-year-old Austrian girls (20%). Being overweight or obese at the
      age of 6 years increased the risk of being overweight at 10 and 15 years
      significantly (P < 0.001). Among migrants, this risk was significantly higher
      than among Austrian girls (P < 0.001). Only 64.8% of Austrian girls, who were
      overweight/obese at the age of 6 years, were still classified as overweight at
      the age of 15 years. Among migrant girls, who were overweight at the age of 6
      years, 72.0% (Turkish girls) and 78.3% (Yugoslavian girls) remained overweight
      until the age of 15 years. CONCLUSIONS: Especially girls from former Yugoslavia
      but also Turkish girls exhibited high rates of overweight and obesity. Prevention
      should start as early as possible since overweight tends to persist from
      childhood into adolescence.

PMID- 16945118
TI  - Obesity as a risk factor for development and poor prognosis of breast cancer.
AB  - The evidence that obesity adversely affects women's health is overwhelming and
      indisputable. The risk of postmenopausal breast cancer increases with obesity;
      measured as weight gain, body mass index, waist-hip ratio or percent body fat. It
      is also established that obesity is associated with poor prognosis of breast
      cancer. This review examines in detail the possible mechanisms by which obesity
      causes poor prognosis of breast cancer such as estrogenic activity, advanced or
      more aggressive disease at diagnosis and high likelihood of both local and
      systemic treatment failure. After careful consideration of the available
      evidence, the author concludes that obesity contributes towards development and
      poor prognosis of breast cancer; therefore, weight management should be an
      integral part of any strategy to prevent and improve the outcome of breast
      cancer.

PMID- 16945119
TI  - The use of three-dimensional computed tomography for assessing patients before
      laparoscopic adrenal-sparing surgery.
AB  - OBJECTIVE: To evaluate the efficacy of three-dimensional computed tomography (3D
      CT) in delineating the relationship of the adrenal mass to adjacent normal
      structures in preparation for laparoscopic partial adrenalectomy. PATIENTS AND
      METHODS: Multislice CT (1 mm slices, 0.5 s rotation time) was used to evaluate 12
      patients before adrenal-sparing surgery for aldosterone-producing adenoma or
      phaeochromocytoma. The CT data were reconstructed using two rendering techniques;
      (i) volume rendering with the modified VOLREN software (Johns Hopkins Hospital,
      Baltimore, MD, USA) which allowed interactive 3D examination of the whole data
      volume within a few minutes; (ii) surface representations only of the interesting
      structures (kidney, adrenal tumour, vessels) represented in different colours and
      depicted together in a 3D scene using the software package 3DVIEWNIX. RESULTS: In
      all, 14 adrenal masses in 12 patients were evaluated with 3D-CT; the number and
      location of lesions was accurate in all cases with both rendering techniques. The
      coloured surface-rendered images showed a consistently better delineation of the
      adrenal tumour from the normal tissue than did the volume-rendering technique.
      From this information all laparoscopic partial adrenalectomies could be completed
      as planned. CONCLUSIONS: Interactive visualization of volume-rendered CT images
      was helpful for the planning and successful performance of the procedure, but
      coloured surface-rendered CT provided more convenient, immediate and accurate
      intraoperative information.

PMID- 16945120
TI  - Detection of clinical unilateral T3a prostate cancer - by digital rectal
      examination or transrectal ultrasonography?
AB  - OBJECTIVE: To assess, in a retrospective study, the sensitivity, specificity,
      positive predictive value (PPV) and negative predictive value (NPV) of digital
      rectal examination (DRE), transrectal ultrasonography (TRUS) and the combination
      of both in unilateral clinical T3a (cT3a) prostate cancer. PATIENTS AND METHODS:
      The long-term outcome of surgical treatment for locally advanced prostate cancer
      is very good and surpasses that for radiotherapy outcomes, so it is anticipated
      that surgical management for cT3a disease will become more important, but staging
      methods for cT3a disease are not well studied. Between 1990 and 2004, 2240
      patients had a radical prostatectomy at our institution; 267 were diagnosed as
      having clinical cT3a prostate cancer either by DRE or TRUS. The final
      histopathology was compared with the findings of DRE and TRUS. The sensitivity,
      specificity, PPV and NPV for DRE, TRUS and the combination of both were
      calculated. RESULTS: The sensitivity, specificity, PPV and NPV by DRE only was
      90.9%, 15.8%, 47.2% and 67.7%, by TRUS only was 80.2%, 25.3%, 47.1% and 60.7%,
      and by both DRE and TRUS was 71.1%, 41.1%, 50.0% and 63.2%. Although the
      sensitivity was lower in the combined group, it had the highest specificity
      (41.1%) and PPV (50.0%). The combination of DRE and TRUS can detect T3a prostate
      cancer more accurately than either method alone. CONCLUSION: Until data on
      staging methods like magnetic resonance imaging become available, the combination
      of DRE and TRUS is advisable in selecting cT3a patients for primary radical
      prostatectomy.

PMID- 16945121
TI  - Silodosin, a new alpha1A-adrenoceptor-selective antagonist for treating benign
      prostatic hyperplasia: results of a phase III randomized, placebo-controlled,
      double-blind study in Japanese men.
AB  - OBJECTIVE: To verify the efficacy and safety of the new alpha1A-adrenoceptor
      selective antagonist silodosin compared with tamsulosin and placebo in patients
      with lower urinary tract symptoms (LUTS) associated with benign prostatic
      hyperplasia (BPH). PATIENTS AND METHODS: This randomized, double-blind, placebo
      controlled study was conducted at 88 centres in Japan. Men aged > or = 50 years
      with an International Prostate Symptom Score (IPSS) of > or = 8, a quality-of
      life (QoL) score of > or = 3, a maximum urinary flow rate (Qmax) of < 15 mL/s, a
      prostate volume of > or = 20 mL and a postvoid residual urine volume of < 100 mL
      were eligible for enrolment. Patients were randomized to receive silodosin 4 mg
      twice daily, tamsulosin 0.2 mg once daily, or placebo, for 12 weeks. The primary
      endpoint was the change in IPSS from baseline. Safety was assessed by adverse
      events, physical examination, vital signs and laboratory tests. RESULTS: In all,
      457 patients were randomized (silodosin 176, tamsulosin 192 and placebo 89). The
      change in the total IPSS from baseline in the silodosin, tamsulosin and placebo
      groups was -8.3, -6.8 and -5.3, respectively. There was a significant decrease in
      the IPSS vs placebo in the silodosin group from 1 week. In the early-stage
      comparison, silodosin showed a significant decrease in IPSS vs tamsulosin at 2
      weeks. The change in QoL from baseline was -1.7, -1.4 and -1.1 in the silodosin,
      tamsulosin and placebo groups, respectively; silodosin showed a significant
      improvement in the QoL score vs placebo. In the subgroup of patients with severe
      symptoms (IPSS > or = 20) silodosin also gave a significantly better improvement
      than placebo (-12.4 vs -8.7). The incidence rates of adverse events and drug
      related adverse events were, respectively, 88.6%, 82.3% and 71.6% and 69.7%,
      47.4% and 36.4%, respectively. The most common adverse event in the silodosin
      group was abnormal ejaculation, which occurred more often in the silodosin than
      in the tamsulosin group (22.3% vs 1.6%). However, only five men (2.9%)
      discontinued treatment for abnormal ejaculation. CONCLUSION: Silodosin was
      generally effective in the absence of obtrusive side-effects. This study suggests
      that silodosin is clinically useful for treating LUTS associated with BPH.

PMID- 16945122
TI  - Human nasal rhinosporidiosis: an Italian case report.
AB  - BACKGROUND: Rhinosporidiosis is a disease affecting primarily the mucosa of nose,
      conjunctiva and urethra. It is endemic in some Asiatic regions, affecting people
      of any age and sex. Its manifestation is a polypoid mass growing inside the
      affected cavity and the only treatment is surgical excision. Rhinosporidium
      seeberi is the aetiological agent. Many discussions arouse regarding the
      taxonomic classification of the microorganism, recent studies established it is
      an aquatic protistan parasite. The lesion may recur and sometimes cause
      osteolytic bone lesions. In endemic areas it is not easy to establish if
      recurrent lesions are due to relapse or reinfection. CASE PRESENTATION: A 26-year
      old male patient from India, resident in Italy since 2005, presented in March
      2006 with a history of nasal obstruction of three months duration. Physical
      examination showed an erythematous, papillomatous mass, 3 cm in diameter,
      obstructing the right nasal cavity. A microscopic diagnosis of rhinosporidiosis
      was made. Few Italian human cases of this disease have been previously reported
      in the literature. CONCLUSION: Rhinosporidiosis is a condition which both
      clinicians and pathologists should keep in mind when managing patients from
      endemic countries with nasal masses. Moreover, it is very interesting in such
      cases to follow the clinical course: an eventual recurrence of the lesion in our
      patient would mean a true relapse, excluding the possibility of a reinfection,
      more probable in the endemic areas.

PMID- 16945123
TI  - Prognostic significance of urokinase plasminogen activator and plasminogen
      activator inhibitor-1 mRNA expression in lymph node- and hormone receptor
      positive breast cancer.
AB  - BACKGROUND: One of the most thoroughly studied systems in relation to its
      prognostic relevance in patients with breast cancer, is the plasminogen
      activation system that comprises of, among others, the urokinase Plasminogen
      Activator (uPA) and its main inhibitor, the Plasminogen Activator Inhibitor-1
      (PAI-1). In this study, we investigated the prognostic value of uPA and PAI-1 at
      the mRNA level in lymph node- and hormone receptor-positive breast cancer.
      METHODS: The study included a retrospective series of 87 patients with hormone
      receptor positive and axillary lymph node-positive breast cancer. All patients
      received radiotherapy, adjuvant anthracycline-based chemotherapy and five years
      of tamoxifen treatment. The median patient age was 54 and the median follow-up
      time was 79 months. Distant relapse occurred in 30 patients and 22 patients died
      from breast cancer during follow-up. We investigated the prognostic value of uPA
      and PAI-1 at the mRNA level as measured by real-time quantitative RT-PCR.
      RESULTS: uPA and PAI-1 gene expression was not found to be correlated with any of
      the established clinical and pathological factors. Metastasis-free Survival (MFS)
      and Breast Cancer specific Survival (BCS) were significantly shorter in patients
      expressing high levels of PAI-1 mRNA (p < 0.0001; p < 0.0001; respectively). In
      Cox multivariate analysis, the level of PAI-1 mRNA appeared to be the strongest
      prognostic factor for MFS (Hazard Ratio (HR) = 10.12; p = 0.0002) and for BCS (HR
      = 13.17; p = 0.0003). Furthermore, uPA gene expression was not significantly
      associated neither with MFS (p = 0.41) nor with BCS (p = 0.19). In a Cox
      multivariate regression analysis, uPA expression did not demonstrate significant
      independent prognostic value. CONCLUSION: These findings indicate that high PAI-1
      mRNA expression represents a strong and independent unfavorable prognostic factor
      for the development of metastases and for breast cancer specific survival in a
      population of hormone receptor- and lymph node-positive breast cancer patients.

PMID- 16945125
TI  - Phenology of marine turtle nesting revealed by statistical model of the nesting
      season.
AB  - BACKGROUND: Marine turtles deposit their eggs on tropical or subtropical beaches
      during discrete nesting seasons that span several months. The number and
      distribution of nests laid during a nesting season provide vital information on
      various aspects of marine turtle ecology and conservation. RESULTS: In the case
      of leatherback sea turtles nesting in French Guiana, we developed a mathematical
      model to explore the phenology of their nesting season, derived from an
      incomplete nest count dataset. We detected 3 primary components in the nest
      distribution of leatherbacks: an overall shape that corresponds to the arrival
      and departure of leatherback females in the Guianas region, a sinusoidal pattern
      with a period of approximately 10 days that is related to physiological
      constraints of nesting female leatherbacks, and a sinusoidal pattern with a
      period of approximately 15 days that likely reflects the influence of spring high
      tides on nesting female turtles. CONCLUSION: The model proposed here offers a
      variety of uses for both marine turtles and also other taxa when individuals are
      observed in a particular location for only part of the year.

PMID- 16945124
TI  - Emergency laparoscopy--current best practice.
AB  - Emergency laparoscopic surgery allows both the evaluation of acute abdominal pain
      and the treatment of many common acute abdominal disorders. This review
      critically evaluates the current evidence base for the use of laparoscopy, both
      diagnostic and interventional, in the emergency abdomen, and provides guidance
      for surgeons as to current best practise. Laparoscopic surgery is firmly
      established as the best intervention in acute appendicitis, acute cholecystitis
      and most gynaecological emergencies but requires further randomised controlled
      trials to definitively establish its role in other conditions.

PMID- 16945126
TI  - New low-viscosity overlay medium for viral plaque assays.
AB  - BACKGROUND: Plaque assays in cell culture monolayers under solid or semisolid
      overlay media are commonly used for quantification of viruses and antiviral
      substances. To overcome the pitfalls of known overlays, we tested suspensions of
      microcrystalline cellulose Avicel RC/CLtrade mark as overlay media in the plaque
      and plaque-inhibition assay of influenza viruses. RESULTS: Significantly larger
      plaques were formed under Avicel-containing media, as compared to agar and
      methylcellulose (MC) overlay media. The plaque size increased with decreasing
      Avicel concentration, but even very diluted Avicel overlays (0.3%) ensured
      formation of localized plaques. Due to their low viscosity, Avicel overlays were
      easier to use than methylcellulose overlays, especially in the 96-well culture
      plates. Furthermore, Avicel overlay could be applied without prior removal of the
      virus inoculum thus facilitating the assay and reducing chances of cross
      contamination. Using neuraminidase inhibitor oseltamivir carboxylate, we
      demonstrated applicability of the Avicel-based plaque reduction assay for testing
      of antiviral substances. CONCLUSION: Plaque assay under Avicel-containing overlay
      media is easier, faster and more sensitive than assays under agar- and
      methylcellulose overlays. The assay can be readily performed in a 96-well plate
      format and seems particularly suitable for high-throughput virus titrations,
      serological studies and experiments on viral drug sensitivity. It may also
      facilitate work with highly pathogenic agents performed under hampered conditions
      of bio-safety labs.

PMID- 16945127
TI  - The effect of long term combined yoga practice on the basal metabolic rate of
      healthy adults.
AB  - BACKGROUND: Different procedures practiced in yoga have stimulatory or inhibitory
      effects on the basal metabolic rate when studied acutely. In daily life however,
      these procedures are usually practiced in combination. The purpose of the present
      study was to investigate the net change in the basal metabolic rate (BMR) of
      individuals actively engaging in a combination of yoga practices (asana or yogic
      postures, meditation and pranayama or breathing exercises) for a minimum period
      of six months, at a residential yoga education and research center at Bangalore.
      METHODS: The measured BMR of individuals practicing yoga through a combination of
      practices was compared with that of control subjects who did not practice yoga
      but led similar lifestyles. RESULTS: The BMR of the yoga practitioners was
      significantly lower than that of the non-yoga group, and was lower by about 13 %
      when adjusted for body weight (P < 0.001). This difference persisted when the
      groups were stratified by gender; however, the difference in BMR adjusted for
      body weight was greater in women than men (about 8 and 18% respectively). In
      addition, the mean BMR of the yoga group was significantly lower than their
      predicted values, while the mean BMR of non-yoga group was comparable with their
      predicted values derived from 1985 WHO/FAO/UNU predictive equations. CONCLUSION:
      This study shows that there is a significantly reduced BMR, probably linked to
      reduced arousal, with the long term practice of yoga using a combination of
      stimulatory and inhibitory yogic practices.

PMID- 16945128
TI  - Preventive home visits postpone mortality--a controlled trial with time-limited
      results.
AB  - BACKGROUND: There is a debate on whether preventive home visits to older people
      have any impact. This study was undertaken to investigate whether preventive home
      visits by professional health workers to older persons can postpone mortality in
      a Swedish context. METHOD: A controlled trial in a small community in the north
      of Sweden. Participants are healthy pensioners aged 75 years and over. 196
      pensioners were selected as the intervention group and 346 as the control group.
      The intervention, two visits per year, lasted two years. RESULTS: During the
      intervention, mortality was 27 per 1000 in the intervention group and 48 per 1000
      in the control group. The incidence rate ratio for the control group IR2000-2001
      was 1.79 (95% CI = 0.94-3.40). Analysing the data with an "on treatment approach"
      gave a significant result, 2.31 (95% CI = 1.07-5.02) After the trial the
      difference between the groups disappeared. CONCLUSION: Preventive home visits in
      a healthy older population can postpone mortality in a Swedish context if they
      are carried out by professional health-workers in a structured way. When the home
      visit programme ended the effect on mortality disappeared. These findings are
      dependent on contextual factors that make it difficult to form general policy
      recommendations.

PMID- 16945129
TI  - Ethnopharmacological evaluation of radal (leaves of Lomatia hirsuta) and
      isolation of 2-methoxyjuglone.
AB  - BACKGROUND: Leaves of Lomatia hirsuta are used in traditional medicine in Chile
      under the common name of "radal". A tea of radal is traditionally used for
      treatment of cough, bronchial troubles, and asthma. In a preliminary screening,
      extracts of the leaves revealed antifungal activity, and the present
      phytochemical study was undertaken to explain this activity and support the
      traditional use. METHODS: Along with the traditional tea, extracts of the leaves
      were screened for antifungal and toxic activities. The profile of secondary
      constituents was obtained using GC-MS. RESULTS: 2-Methoxyjuglone was isolated
      from the leaves of Lomatia hirsuta and found to be active against the pathogenic
      fungus Candida albicans (MIC = 8 microg/mL). Cinnamic acid and vanillic acid were
      identified as major constituents in the tea by GC-MS. The tea was found not to be
      toxic against Artemia salina. CONCLUSION: The presence of phenolic acids with
      antimicrobial properties supports the traditional use of Radal, and encourages
      further studies.

PMID- 16945130
TI  - A randomised controlled trial investigating the effect of n-3 long-chain
      polyunsaturated fatty acid supplementation on cognitive and retinal function in
      cognitively healthy older people: the Older People And n-3 Long-chain
      polyunsaturated fatty acids (OPAL) study protocol [ISRCTN72331636].
AB  - The number of individuals with age-related cognitive impairment is rising
      dramatically in the UK and globally. There is considerable interest in the
      general hypothesis that improving the diet of older people may slow the
      progression of cognitive decline. To date, there has been little attention given
      to the possible protective role of n-3 long-chain polyunsaturated fatty acids (n
      3 LCPs) most commonly found in oily fish, in age-related loss of cognitive
      function. The main research hypothesis of this study is that an increased dietary
      intake of n-3 LCPs will have a positive effect on cognitive performance in older
      people in the UK. To test this hypothesis, a double-blind randomised placebo
      controlled trial will be carried out among adults aged 70-79 years in which the
      intervention arm will receive daily capsules containing n-3 LCP (0.5 g/day
      docosahexaenoic acid and 0.2 g/day eicosapentaenoic acid) while the placebo arm
      will receive daily capsules containing olive oil. The main outcome variable
      assessed at 24 months will be cognitive performance and a second major outcome
      variable will be retinal function. Retinal function tests are included as the
      retina is a specifically differentiated neural tissue and therefore represents an
      accessible window into the functioning of the brain. The overall purpose of this
      public-health research is to help define a simple and effective dietary
      intervention aimed at maintaining cognitive and retinal function in later life.
      This will be the first trial of its kind aiming to slow the decline of cognitive
      and retinal function in older people by increasing daily dietary intake of n-3
      LCPs. The link between cognitive ability, visual function and quality of life
      among older people suggests that this novel line of research may have
      considerable public health importance.

PMID- 16945131
TI  - Semi-automated segmentation and quantification of adipose tissue in calf and
      thigh by MRI: a preliminary study in patients with monogenic metabolic syndrome.
AB  - BACKGROUND: With the growing prevalence of obesity and metabolic syndrome,
      reliable quantitative imaging methods for adipose tissue are required. Monogenic
      forms of the metabolic syndrome include Dunnigan-variety familial partial
      lipodystrophy subtypes 2 and 3 (FPLD2 and FPLD3), which are characterized by the
      loss of subcutaneous fat in the extremities. Through magnetic resonance imaging
      (MRI) of FPLD patients, we have developed a method of quantifying the core FPLD
      anthropometric phenotype, namely adipose tissue in the mid-calf and mid-thigh
      regions. METHODS: Four female subjects, including an FPLD2 subject (LMNA R482Q),
      an FPLD3 subject (PPARG F388L), and two control subjects were selected for MRI
      and analysis. MRI scans of subjects were performed on a 1.5T GE MR Medical
      system, with 17 transaxial slices comprising a 51 mm section obtained in both the
      mid-calf and mid-thigh regions. Using ImageJ 1.34 n software, analysis of raw MR
      images involved the creation of a connectedness map of the subcutaneous adipose
      tissue contours within the lower limb segment from a user-defined seed point.
      Quantification of the adipose tissue was then obtained after thresholding the
      connected map and counting the voxels (volumetric pixels) present within the
      specified region. RESULTS: MR images revealed significant differences in the
      amounts of subcutaneous adipose tissue in lower limb segments of FPLD3 and FPLD2
      subjects: respectively, mid-calf, 15.5% and 0%, and mid-thigh, 25.0% and 13.3%.
      In comparison, old and young healthy controls had values, respectively, of mid
      calf, 32.5% and 26.2%, and mid-thigh, 52.2% and 36.1%. The FPLD2 patient had
      significantly reduced subcutaneous adipose tissue compared to FPLD3 patient.
      CONCLUSION: Thus, semi-automated quantification of adipose tissue of the lower
      extremity can detect differences between individuals of various lipodystrophy
      genotypes and represents a potentially useful tool for extended quantitative
      phenotypic analysis of other genetic metabolic disorders.

PMID- 16945132
TI  - Predicting transcription factor binding sites using local over-representation and
      comparative genomics.
AB  - BACKGROUND: Identifying cis-regulatory elements is crucial to understanding gene
      expression, which highlights the importance of the computational detection of
      overrepresented transcription factor binding sites (TFBSs) in coexpressed or
      coregulated genes. However, this is a challenging problem, especially when
      considering higher eukaryotic organisms. RESULTS: We have developed a method,
      named TFM-Explorer, that searches for locally overrepresented TFBSs in a set of
      coregulated genes, which are modeled by profiles provided by a database of
      position weight matrices. The novelty of the method is that it takes advantage of
      spatial conservation in the sequence and supports multiple species. The
      efficiency of the underlying algorithm and its robustness to noise allow weak
      regulatory signals to be detected in large heterogeneous data sets. CONCLUSION:
      TFM-Explorer provides an efficient way to predict TFBS overrepresentation in
      related sequences. Promising results were obtained in a variety of examples in
      human, mouse, and rat genomes. The software is publicly available at
      http://bioinfo.lifl.fr/TFM-Explorer.

PMID- 16945133
TI  - Ruptured renal artery aneurysm during pregnancy, a clinical dilemma.
AB  - BACKGROUND: Rupture of a renal artery aneurysm (RAA) during pregnancy is a rare
      event, with a high mortality rate for both mother and fetus. Increased blood flow
      and intra-abdominal pressure, and vascular changes secondary to increased steroid
      production are postulated as contributory to the increased risk of rupture during
      pregnancy. CASE PRESENTATION: We present here a case report of total avulsion of
      solitary kidney secondary to rupture of RAA in a pregnant patient with congenital
      absence of the contralateral kidney. The main indication for nephrectomy was
      severely damaged kidney. Diagnosis was made during operation and both mother and
      fetus were saved. There are no previous reports of an intact renal artery
      aneurysm diagnosed either antepartum or postpartum. CONCLUSION: The possibility
      of a ruptured RAA should be considered in pregnant women with evidence of
      retroperitoneal hemorrhage. This case was unusual because it occurred in a
      solitary kidney, during the third trimester of pregnancy.

PMID- 16945134
TI  - Protein expression of G-protein inwardly rectifying potassium channels (GIRK) in
      breast cancer cells.
AB  - BACKGROUND: Previous data from our laboratory has indicated that a functional
      link exists between the G-protein-coupled inwardly rectifying potassium (GIRK)
      channel and the beta-adrenergic receptor pathway in breast cancer cell lines, and
      these pathways were involved in growth regulation of these cells. Alcohol is an
      established risk factor for breast cancer and has been found to open GIRK. In
      order to further investigate GIRK channels in breast cancer and possible
      alteration by ethanol, we identified GIRK channel protein expression in breast
      cancer cells. RESULTS: Cell pellets were collected and membrane protein was
      isolated to determine GIRK protein expression. GIRK protein was also analyzed by
      immuno-precipitation. GIRK protein was over-expressed in cells by transfection of
      GIRK plasmids. Gene expression studies were done by real-time RT-PCR. GIRK
      protein expression was identified in breast cancer cell lines. Expression of
      GIRK1 at the indicated molecular weight (MW) (62 kDa) was seen in cell lines MDA
      MB-453 and ZR-75-1. In addition, GIRK1 expression was seen at a lower MW (40-42
      kDa) in MDA-MB-361, MDA-MB-468, MCF-7, ZR-75-1, and MDA-MB-453 cell lines. To
      prove the lower MW protein was GIRK1, MDA-MB-453 cells were immuno-precipitated.
      GIRK2 expression was seen in MDA-MB-468, MCF-7, and ZR-75-1 and was variable in
      MDA-MB-453, while GIRK4 protein expression was seen in all six cell lines tested.
      This is the first report indicating GIRK protein expression in breast cancer
      cells. To determine functionality, MDA-MB-453 cells were stimulated with ethanol.
      Decreased GIRK1 protein expression levels were seen after treatment with 0.12%
      ethanol in MDA-MB-453 breast cancer cells. Serum-free media decreased GIRK
      protein expression, possibly due to lack of estrogen in the media. Transfection
      of GIRK1 or GIRK4 plasmids increased GIRK1 protein expression and decreased gene
      expression in MDA-MB-453 breast cancer cells. CONCLUSION: Our data indicates that
      functional GIRK channels exist in breast cancer cells that are involved in
      cellular signaling.

PMID- 16945135
TI  - Bacterial lipopolysaccharide induces apoptosis in the trout ovary.
AB  - BACKGROUND: In mammals it is well known that infections can lead to alterations
      in reproductive function. As part of the innate immune response, a number of
      cytokines and other immune factors is produced during bacterial infection or
      after treatment with lipopolysaccharide (LPS) and acts on the reproductive
      system. In fish, LPS can also induce an innate immune response but little is
      known about the activation of the immune system by LPS on reproduction in fish.
      Therefore, we conducted studies to examine the in vivo and in vitro effects of
      lipopolysaccharide (LPS) on the reproductive function of sexually mature female
      trout. METHODS: In saline- and LPS -injected brook trout, we measured the
      concentration of plasma steroids as well as the in vitro steroidogenic response
      (testosterone and 17alpha-hydroxyprogesterone) of ovarian follicles to
      luteinizing hormone (LH), the ability of 17alpha,20beta-dihydroxy-4-pregnen-3-one
      to induce germinal vesicle breakdown (GVBD) in vitro, and that of epinephrine to
      stimulate follicular contraction in vitro. We also examined the direct effects of
      LPS in vitro on steroid production, GVBD and contraction in brook trout ovarian
      follicles. The incidence of apoptosis was evaluated by TUNEL analysis.
      Furthermore, we examined the gene expression pattern in the ovary of saline- and
      LPS-injected rainbow trout by microarray analysis. RESULTS: LPS treatment in vivo
      did not affect plasma testosterone concentration or the basal in vitro production
      of steroids, although a small but significant potentiation of the effects of LH
      on testosterone production in vitro was observed in ovarian follicles from LPS
      treated fish. In addition, LPS increased the plasma concentration of cortisol.
      LPS treatment in vitro did not affect the basal or LH-stimulated steroid
      production in brook trout ovarian follicles. In addition, we did not observe any
      effects of LPS in vivo or in vitro on GVBD or follicular contraction. Therefore,
      LPS did not appear to impair ovarian steroid production, oocyte final maturation
      or follicular contraction under the present experimental conditions.
      Interestingly, LPS administration in vivo induced apoptosis in follicular cells,
      an observation that correlated with changes in the expression of genes involved
      in apoptosis, as evidenced by microarray analysis. CONCLUSION: These results
      indicate that female trout are particularly resistant to an acute administration
      of LPS in terms of ovarian hormone responsiveness. However, LPS caused a marked
      increase in apoptosis in follicular cells, suggesting that the trout ovary could
      be sensitive to the pro-apoptotic effects of LPS-induced inflammatory cytokines.

PMID- 16945136
TI  - Gene x Gene interaction between MnSOD and GPX-1 and breast cancer risk: a nested
      case-control study.
AB  - BACKGROUND: Germ-line mutations in genes such as BRCA1, BRCA2, and ATM can cause
      a substantial increase in risk of breast cancer. However, these mutations are
      rare in the general population, and account for little of the incidence of
      sporadic breast cancer in the general population. Therefore, research has been
      focused on examining associations between common polymorphisms and breast cancer
      risk. To date, few associations have been described. This has led to the
      hypothesis that breast cancer is a complex disease, whereby a constellation of
      very low penetrance alleles need to be carried to present a risk phenotype.
      Polymorphisms in the manganese superoxide dismutase (MnSOD) and glutathione
      peroxidase (GPX-1) genes have been proposed as low penetrance alleles, and have
      not been clearly associated with breast cancer. We investigated whether variants
      at both polymorphisms, while not independently associated with breast cancer
      risk, could influence breast cancer risk when considered together. METHODS: A
      case-control study nested within the Nurses' Health Study was performed comparing
      1262 women diagnosed with breast cancer to 1533 disease free women. The MnSOD
      (Val16Ala, rs1799725) and GPX-1 (Pro198Leu, rs1050450) were genotyped via TaqMan
      assay. Disease risk was evaluated using logistic regression. RESULTS: While
      neither allele alone shows any change in breast cancer risk, an increase in the
      risk of breast cancer (OR 1.87, 95% CI 1.09 - 3.19) is observed in individuals
      who carry both the Ala16Ala genotype of MnSOD and the Leu198Leu genotype of GPX
      1. CONCLUSION: Polymorphisms in the GPX-1 and MnSOD genes are associated with an
      increased risk of breast cancer.

PMID- 16945137
TI  - Analysis of vaccinia virus temperature-sensitive I7L mutants reveals two
      potential functional domains.
AB  - As an approach to initiating a structure-function analysis of the vaccinia virus
      I7L core protein proteinase, a collection of conditional-lethal mutants in which
      the mutation had been mapped to the I7L locus were subjected to genomic
      sequencing and phenotypic analyses. Mutations in six vaccinia virus I7L
      temperature sensitive mutants fall into two groups: changes at three positions at
      the N-terminal end between amino acids 29 and 37 and two different substitutions
      at amino acid 344, near the catalytic domain. Regardless of the position of the
      mutation, mutants at the non-permissive temperature failed to cleave core protein
      precursors and had their development arrested prior to core condensation. Thus it
      appears that the two clusters of mutations may affect two different functional
      domains required for proteinase activity.

PMID- 16945138
TI  - Heritability and major gene effects on left ventricular mass in the Chinese
      population: a family study.
AB  - BACKGROUND: Genetic components controlling for echocardiographically determined
      left ventricular (LV) mass are still unclear in the Chinese population. METHODS:
      We conducted a family study from the Chin-San community, Taiwan, and a total of
      368 families, 1145 subjects, were recruited to undergo echocardiography to
      measure LV mass. Commingling analysis, familial correlation, and complex
      segregation analysis were applied to detect component distributions and the mode
      of inheritance. RESULTS: The two-component distribution model was the best
      fitting model to describe the distribution of LV mass. The highest familial
      correlation coefficients were mother-son (0.379, P < .0001) and father-son
      (0.356, P < .0001). Genetic heritability (h2) of LV mass was estimated as 0.268
      +/- 0.061 (P < .0001); it decreased to 0.153 +/- 0.052 (P = .0009) after systolic
      blood pressure adjustment. Major gene effects with polygenic components were the
      best-fitting model to explain the inheritance mode of LV mass. The estimated
      allele frequency of the gene was 0.089. CONCLUSION: There were significant
      familial correlations, heritability and a major gene effect on LV mass in the
      population-based families.

PMID- 16945139
TI  - Evaluation of ultrasound lung comets by hand-held echocardiography.
AB  - BACKGROUND: Ultrasound lung comets (ULCs) are a clinically useful sign of
      extravascular lung water. They require very limited technology (2 D-echo), and a
      short learning curve. The aim of the present study is to compare ULCs information
      obtained by experienced echocardiologists using a full feature echocardiographic
      platform and by inexperienced sonographers using a hand-held echocardiography
      system. METHODS: 20 consecutive in-hospital patients underwent, within 15' and in
      random order, 2 ultrasound examinations for ULCs by 2 observers with different
      specific expertise and different technology: 1) "high-tech veteran": ULCs
      assessment with full feature echocardiographic platform (HP Sonos 7500 Philips
      Medical Systems, Andover, MA, USA) by a trained echocardiologist, with > or =2
      years expertise in ULCs assessment and accredited by the European Association of
      Echocardiography; 2) and a "low-tech beginner": ULCs assessment with hand-held
      echocardiography (Optigo; Philips, Andover, MA) by an echocardiographer with very
      limited (30') dedicated training on ULCs assessment. In each patient, ULC score
      was obtained by summing the number of comets from each of the scanning spaces in
      the anterior right and left hemithorax, from the second to the fifth intercostal
      space. RESULTS: There was a significant, tight correlation (r = .958, p < 0.001)
      between the 2 observations in the same patient by "high-tech veteran" and "low
      tech beginner". CONCLUSION: ULCs are equally reliable in the hands of highly
      experienced echocardiologists using full feature echocardiographic platforms and
      in the hands of absolute beginners with miniaturized, compact, and battery
      equipped echocardiographic systems. From the technological and expertise
      viewpoint, ULCs are the "kindergarten" of echocardiography, ideally suited for
      bedside evaluation of patients with both known or suspected heart failure.

PMID- 16945141
TI  - Fine mapping of genes within the IDDM8 region in rheumatoid arthritis.
AB  - The IDDM8 region on chromosome 6q27, first identified as a susceptibility locus
      for type 1 diabetes, has previously been linked and associated with rheumatoid
      arthritis (RA). The region contains a number of potential candidate genes,
      including programmed cell death 2 (PDCD2), the proteosome subunit beta type 1
      (PSMB1), delta-like ligand 1 (DLL-1) and TATA box-binding protein (TBP) amongst
      others. The aim of this study was to fine map the IDDM8 region on chromosome
      6q27, focusing on the genes in the region, to identify polymorphisms that may
      contribute to susceptibility to RA and potentially to other autoimmune diseases.
      Validated single nucleotide polymorphisms (SNPs; n = 65) were selected from
      public databases from the 330 kb region of IDDM8. These were genotyped using
      Sequenom MassArray genotyping technology in two datasets; the test dataset
      comprised 180 RA cases and 180 controls. We tested 50 SNPs for association with
      RA and any significant associations were genotyped in a second dataset of 174 RA
      cases and 192 controls, and the datasets were combined before analysis.
      Association analysis was performed by chi-square test implemented in Stata
      software and linkage disequilibrium and haplotype analysis was performed using
      Helix tree version 4.1. There was initial weak evidence of association, with RA,
      of a number of SNPs around the loc154449 putative gene and within the KIAA1838
      gene; however, these associations were not significant in the combined dataset.
      Our study has failed to detect evidence of association with any of the known
      genes mapping to the IDDM8 locus with RA.

PMID- 16945142
TI  - Optimization of a large-scale gene disruption protocol in Dictyostelium and
      analysis of conserved genes of unknown function.
AB  - BACKGROUND: Development of the post-genomic age in Dictyostelium will require the
      existence of rapid and reliable methods to disrupt genes that would allow the
      analysis of entire gene families and perhaps the possibility to undertake the
      complete knock-out analysis of all the protein-coding genes present in
      Dictyostelium genome. RESULTS: Here we present an optimized protocol based on the
      previously described construction of gene disruption vectors by in vitro
      transposition. Our method allows a rapid selection of the construct by a simple
      PCR approach and subsequent sequencing. Disruption constructs were amplified by
      PCR and the products were directly transformed in Dictyostelium cells. The
      selection of homologous recombination events was also performed by PCR. We have
      constructed 41 disruption vectors to target genes of unknown function, highly
      conserved between Dictyostelium and human, but absent from the genomes of S.
      cerevisiae and S. pombe. 28 genes were successfully disrupted. CONCLUSION: This
      is the first step towards the understanding of the function of these conserved
      genes and exemplifies the easiness to undertake large-scale disruption analysis
      in Dictyostelium.

PMID- 16945140
TI  - Complete plastid genome sequence of Daucus carota: implications for biotechnology
      and phylogeny of angiosperms.
AB  - BACKGROUND: Carrot (Daucus carota) is a major food crop in the US and worldwide.
      Its capacity for storage and its lifecycle as a biennial make it an attractive
      species for the introduction of foreign genes, especially for oral delivery of
      vaccines and other therapeutic proteins. Until recently efforts to express
      recombinant proteins in carrot have had limited success in terms of protein
      accumulation in the edible tap roots. Plastid genetic engineering offers the
      potential to overcome this limitation, as demonstrated by the accumulation of
      BADH in chromoplasts of carrot taproots to confer exceedingly high levels of salt
      resistance. The complete plastid genome of carrot provides essential information
      required for genetic engineering. Additionally, the sequence data add to the
      rapidly growing database of plastid genomes for assessing phylogenetic
      relationships among angiosperms. RESULTS: The complete carrot plastid genome is
      155,911 bp in length, with 115 unique genes and 21 duplicated genes within the
      IR. There are four ribosomal RNAs, 30 distinct tRNA genes and 18 intron
      containing genes. Repeat analysis reveals 12 direct and 2 inverted repeats > or =
      30 bp with a sequence identity > or = 90%. Phylogenetic analysis of nucleotide
      sequences for 61 protein-coding genes using both maximum parsimony (MP) and
      maximum likelihood (ML) were performed for 29 angiosperms. Phylogenies from both
      methods provide strong support for the monophyly of several major angiosperm
      clades, including monocots, eudicots, rosids, asterids, eurosids II, euasterids
      I, and euasterids II. CONCLUSION: The carrot plastid genome contains a number of
      dispersed direct and inverted repeats scattered throughout coding and non-coding
      regions. This is the first sequenced plastid genome of the family Apiaceae and
      only the second published genome sequence of the species-rich euasterid II clade.
      Both MP and ML trees provide very strong support (100% bootstrap) for the sister
      relationship of Daucus with Panax in the euasterid II clade. These results
      provide the best taxon sampling of complete chloroplast genomes and the strongest
      support yet for the sister relationship of Caryophyllales to the asterids. The
      availability of the complete plastid genome sequence should facilitate improved
      transformation efficiency and foreign gene expression in carrot through
      utilization of endogenous flanking sequences and regulatory elements.

PMID- 16945143
TI  - Marginal vitamin C status is associated with reduced fat oxidation during
      submaximal exercise in young adults.
AB  - BACKGROUND: Vitamin C is a cofactor in the biosynthesis of carnitine, a molecule
      required for the oxidation of fatty acids. A reduction in the ability to oxidize
      fat may contribute to the reported inverse relationship between vitamin C status
      and adiposity. To examine this possibility, we conducted a preliminary trial to
      evaluate the impact of vitamin C status on fat oxidation during submaximal
      exercise. METHODS: Fat energy expenditure was determined in individuals with
      marginal (n = 15) or adequate (n = 7) vitamin C status during a submaximal, 60
      minute treadmill test. Subsequently, eight of the subjects with marginal vitamin
      C status completed an 8-week double-blind, placebo-controlled, depletion
      repletion trial with submaximal exercise testing. RESULTS: Individuals with
      marginal vitamin C status oxidized 25% less fat per kg body weight during the
      treadmill test as compared to individuals with adequate vitamin C status. Fat
      oxidation during exercise was inversely related to fatigue (r = -0.611, p =
      0.009). Vitamin C repletion of vitamin C depleted subjects (500 mg vitamin C/d)
      raised fat energy expenditure during exercise 4-fold as compared to depleted
      control subjects (p = 0.011). CONCLUSION: These preliminary results show that low
      vitamin C status is associated with reduced fat oxidation during submaximal
      exercise. Low vitamin C status may partially explain the inverse relationship
      between vitamin C status and adiposity and why some individuals are unsuccessful
      in their weight loss attempts.

PMID- 16945144
TI  - MAP-ping genomic organization and organ-specific expression profiles of poplar
      MAP kinases and MAP kinase kinases.
AB  - BACKGROUND: As in other eukaryotes, plant mitogen-activated protein kinase (MAPK)
      cascades are composed of three classes of hierarchically organized protein
      kinases, namely MAPKKKs, MAPKKs, and MAPKs. These modules rapidly amplify and
      transduce extracellular signals into various appropriate intracellular responses.
      While extensive work has been conducted on the post-translational regulation of
      specific MAPKKs and MAPKs in various plant species, there has been no systematic
      investigation of the genomic organization and transcriptional regulation of these
      genes. RESULTS: Ten putative poplar MAPKK genes (PtMKKs) and 21 putative poplar
      MAPK genes (PtMPKs) have been identified and located within the poplar (Populus
      trichocarpa) genome. Analysis of exon-intron junctions and of intron phase inside
      the predicted coding region of each candidate gene has revealed high levels of
      conservation within and between phylogenetic groups. Expression profiles of all
      members of these two gene families were also analyzed in 17 different poplar
      organs, using gene-specific primers directed at the 3'-untranslated region of
      each candidate gene and real-time quantitative PCR. Most PtMKKs and PtMPKs were
      differentially expressed across this developmental series. CONCLUSION: This
      analysis provides a complete survey of MAPKK and MAPK gene expression profiles in
      poplar, a large woody perennial plant, and thus complements the extensive
      expression profiling data available for the herbaceous annual Arabidopsis
      thaliana. The poplar genome is marked by extensive segmental and chromosomal
      duplications, and within both kinase families, some recently duplicated
      paralogous gene pairs often display markedly different patterns of expression,
      consistent with the rapid evolution of specialized protein functions in this
      highly adaptive species.

PMID- 16945146
TI  - Methods for evaluating clustering algorithms for gene expression data using a
      reference set of functional classes.
AB  - BACKGROUND: A cluster analysis is the most commonly performed procedure (often
      regarded as a first step) on a set of gene expression profiles. In most cases, a
      post hoc analysis is done to see if the genes in the same clusters can be
      functionally correlated. While past successes of such analyses have often been
      reported in a number of microarray studies (most of which used the standard
      hierarchical clustering, UPGMA, with one minus the Pearson's correlation
      coefficient as a measure of dissimilarity), often times such groupings could be
      misleading. More importantly, a systematic evaluation of the entire set of
      clusters produced by such unsupervised procedures is necessary since they also
      contain genes that are seemingly unrelated or may have more than one common
      function. Here we quantify the performance of a given unsupervised clustering
      algorithm applied to a given microarray study in terms of its ability to produce
      biologically meaningful clusters using a reference set of functional classes.
      Such a reference set may come from prior biological knowledge specific to a
      microarray study or may be formed using the growing databases of gene ontologies
      (GO) for the annotated genes of the relevant species. RESULTS: In this paper, we
      introduce two performance measures for evaluating the results of a clustering
      algorithm in its ability to produce biologically meaningful clusters. The first
      measure is a biological homogeneity index (BHI). As the name suggests, it is a
      measure of how biologically homogeneous the clusters are. This can be used to
      quantify the performance of a given clustering algorithm such as UPGMA in
      grouping genes for a particular data set and also for comparing the performance
      of a number of competing clustering algorithms applied to the same data set. The
      second performance measure is called a biological stability index (BSI). For a
      given clustering algorithm and an expression data set, it measures the
      consistency of the clustering algorithm's ability to produce biologically
      meaningful clusters when applied repeatedly to similar data sets. A good
      clustering algorithm should have high BHI and moderate to high BSI. We evaluated
      the performance of ten well known clustering algorithms on two gene expression
      data sets and identified the optimal algorithm in each case. The first data set
      deals with SAGE profiles of differentially expressed tags between normal and
      ductal carcinoma in situ samples of breast cancer patients. The second data set
      contains the expression profiles over time of positively expressed genes (ORF's)
      during sporulation of budding yeast. Two separate choices of the functional
      classes were used for this data set and the results were compared for
      consistency. CONCLUSION: Functional information of annotated genes available from
      various GO databases mined using ontology tools can be used to systematically
      judge the results of an unsupervised clustering algorithm as applied to a gene
      expression data set in clustering genes. This information could be used to select
      the right algorithm from a class of clustering algorithms for the given data set.

PMID- 16945145
TI  - Tying the loose ends together in DNA double strand break repair with 53BP1.
AB  - To maintain genomic stability and ensure the fidelity of chromosomal
      transmission, cells respond to various forms of genotoxic stress, including DNA
      double-stranded breaks (DSBs), through the activation of DNA damage response
      signaling networks. In response to DSBs as induced by ionizing radiation (IR),
      during DNA replication, or through immunoglobulin heavy chain (IgH)
      rearrangements in B cells of lymphoid origin, the phosphatidyl inositol-like
      kinase (PIK) kinases ATM (mutated in ataxia telangiectasia), ATR (ATM and Rad3
      related kinase), and the DNA-dependent protein kinase (DNA-PK) activate signaling
      pathways that lead to DSB repair. DSBs are repaired by either of two major, non
      mutually exclusive pathways: homologous recombination (HR) that utilizes an
      undamaged sister chromatid template (or homologous chromosome) and non-
      homologous end joining (NHEJ), an error prone mechanism that processes and joins
      broken DNA ends through the coordinated effort of a small set of ubiquitous
      factors (DNA-PKcs, Ku70, Ku80, artemis, Xrcc4/DNA lig IV, and XLF/Cernunnos). The
      PIK kinases phosphorylate a variety of effector substrates that propagate the DNA
      damage signal, ultimately resulting in various biological outputs that influence
      cell cycle arrest, transcription, DNA repair, and apoptosis. A variety of data
      has revealed a critical role for p53-binding protein 1 (53BP1) in the cellular
      response to DSBs including various aspects of p53 function. Importantly, 53BP1
      plays a major role in suppressing translocations, particularly in B and T cells.
      This report will review past experiments and current knowledge regarding the role
      of 53BP1 in the DNA damage response.

PMID- 16945147
TI  - Syndecan-1 mediates internalization of apoE-VLDL through a low density
      lipoprotein receptor-related protein (LRP)-independent, non-clathrin-mediated
      pathway.
AB  - BACKGROUND: Triacylglyerol-rich very low density lipoprotein (VLDL) particles are
      the primary carriers of fatty acids in the circulation and as such serve as a
      rich energy source for peripheral tissues. Receptor-mediated uptake of these
      particles is dependent upon prior association with apolipoprotein E (apoE-VLDL)
      and is brought about by cell surface heparan sulfate proteoglycans (HSPG) in some
      cell types and by the low density lipoprotein receptor-related protein (LRP) in
      others. Although LRP's role in apoE-VLDL uptake has been well studied, the
      identity of the HSPG family member that mediates apoE-VLDL uptake has not been
      established. We investigated if syndecan-1 (Syn-1), a transmembrane cell surface
      HSPG, is able to mediate the internalization of apoE-VLDL and examined the
      relationship between Syn-1 and LRP toward apoE-VLDL uptake. For this study, we
      used a human fibroblast cell line (GM00701) that expresses large amounts of LRP,
      but possesses no LDL receptor activity to eliminate its contributions toward apoE
      VLDL uptake. RESULTS: Although LRP in these cells is fully active as established
      by substantial alpha2macroglobulin binding and internalization, uptake of apoE
      VLDL is absent. Expression of human Syn-1 cDNA restored apoE-VLDL binding and
      uptake by these cells. Competition for this uptake with an LRP ligand-binding
      antagonist had little or no effect, whereas co-incubation with heparin abolished
      apoE-VLDL internalization. Depleting Syn-1 expressing cells of K+, to block
      clathrin-mediated endocytosis, showed no inhibition of Syn-1 internalization of
      apoE-VLDL. By contrast, treatment of cells with nystatin to inhibit lipid raft
      function, prevented the uptake of apoE-VLDL by Syn-1. CONCLUSION: These data
      demonstrate that Syn-1 is able to mediate apoE-VLDL uptake in human fibroblasts
      with little or no contribution from LRP and that the endocytic path taken by Syn
      1 is clathrin-independent and relies upon lipid raft function. These data are
      consistent with previous studies demonstrating Syn-1 association with lipid raft
      domains.

PMID- 16945148
TI  - Learning to perform a new movement with robotic assistance: comparison of haptic
      guidance and visual demonstration.
AB  - BACKGROUND: Mechanical guidance with a robotic device is a candidate technique
      for teaching people desired movement patterns during motor rehabilitation,
      surgery, and sports training, but it is unclear how effective this approach is as
      compared to visual demonstration alone. Further, little is known about motor
      learning and retention involved with either robot-mediated mechanical guidance or
      visual demonstration alone. METHODS: Healthy subjects (n = 20) attempted to
      reproduce a novel three-dimensional path after practicing it with mechanical
      guidance from a robot. Subjects viewed their arm as the robot guided it, so this
      "haptic guidance" training condition provided both somatosensory and visual
      input. Learning was compared to reproducing the movement following only visual
      observation of the robot moving along the path, with the hand in the lap (the
      "visual demonstration" training condition). Retention was assessed periodically
      by instructing the subjects to reproduce the path without robotic demonstration.
      RESULTS: Subjects improved in ability to reproduce the path following practice in
      the haptic guidance or visual demonstration training conditions, as evidenced by
      a 30-40% decrease in spatial error across 126 movement attempts in each
      condition. Performance gains were not significantly different between the two
      techniques, but there was a nearly significant trend for the visual demonstration
      condition to be better than the haptic guidance condition (p = 0.09). The 95%
      confidence interval of the mean difference between the techniques was at most 25%
      of the absolute error in the last cycle. When asked to reproduce the path
      repeatedly following either training condition, the subjects' performance
      degraded significantly over the course of a few trials. The tracing errors were
      not random, but instead were consistent with a systematic evolution toward
      another path, as if being drawn to an "attractor path". CONCLUSION: These results
      indicate that both forms of robotic demonstration can improve short-term
      performance of a novel desired path. The availability of both haptic and visual
      input during the haptic guidance condition did not significantly improve
      performance compared to visual input alone in the visual demonstration condition.
      Further, the motor system is inclined to repeat its previous mistakes following
      just a few movements without robotic demonstration, but these systematic errors
      can be reduced with periodic training.

PMID- 16945149
TI  - Familial frontotemporal dementia with neuronal intranuclear inclusions is not a
      polyglutamine expansion disease.
AB  - BACKGROUND: Many cases of frontotemporal dementia (FTD) are familial, often with
      an autosomal dominant pattern of inheritance. Some are due to a mutation in the
      tau- encoding gene, on chromosome 17, and show an accumulation of abnormal tau in
      brain tissue (FTDP-17T). Most of the remaining familial cases do not exhibit tau
      pathology, but display neuropathology similar to patients with dementia and motor
      neuron disease, characterized by the presence of ubiquitin-immunoreactive (ub
      ir), dystrophic neurites and neuronal cytoplasmic inclusions in the neocortex and
      hippocampus (FTLD-U). Recently, we described a subset of patients with familial
      FTD with autopsy-proven FTLD-U pathology and with the additional finding of ub-ir
      neuronal intranuclear inclusions (NII). NII are a characteristic feature of
      several other neurodegenerative conditions for which the genetic basis is
      abnormal expansion of a polyglutamine-encoding trinucleotide repeat region. The
      genetic basis of familial FTLD-U is currently not known, however the presence of
      NII suggests that a subset of cases may represent a polyglutamine expansion
      disease. METHODS: We studied DNA and post mortem brain tissue from 5 affected
      members of 4 different families with NII and one affected individual with
      familial FTLD-U without NII. Patient DNA was screened for CAA/CAG trinucleotide
      expansion in a set of candidate genes identified using a genome-wide
      computational approach. Genes containing CAA/CAG trinucleotide repeats encoding
      at least five glutamines were examined (n = 63), including the nine genes
      currently known to be associated with human disease. CAA/CAG tract sizes were
      compared with published normal values (where available) and with those of healthy
      controls (n = 94). High-resolution agarose gel electrophoresis was used to
      measure allele size (number of CAA/CAG repeats). For any alleles estimated to be
      equal to or larger than the maximum measured in the control population, the
      CAA/CAG tract length was confirmed by capillary electrophoresis. In addition,
      immunohistochemistry using a monoclonal antibody that recognizes proteins
      containing expanded polyglutamines (1C2) was performed on sections of post mortem
      brain tissue from subjects with NII. RESULTS: No significant polyglutamine
      encoding repeat expansions were identified in the DNA from any of our FTLD-U
      patients. NII in the FTLD-U cases showed no 1C2 immunoreactivity. CONCLUSION: We
      find no evidence to suggest that autosomal dominant FTLD-U with NII is a
      polyglutamine expansion disease.

PMID- 16945150
TI  - Benefits and challenges of transitioning preterm infants to at-breast feedings.
AB  - Upon hospital discharge it is not unusual for mothers of preterm infants to
      continue to meet all or most of their infants' nutritional needs through bottle
      feedings of expressed breast milk (EBM) because of infants' physiological
      immaturity and maternal concerns with an inadequacy of milk supply. Although for
      some mothers the challenge of transitioning the infant to feeding at the breast
      may be beyond their ability and resources, for others it appears to be based on a
      conscious choice. Mothers are often unaware of the advantages of breastfeeding at
      the breast. The purpose of this article is to examine some of the factors that
      may contribute to the inability and resistance of mothers to transition their
      preterm infants, and to report on the potential short and long-term advantages
      associated with feeding at the breast as opposed to feeding bottles of EBM.

PMID- 16945151
TI  - Kinesin-5 motors are required for organization of spindle microtubules in
      Silvetia compressa zygotes.
AB  - BACKGROUND: Monastrol, a chemical inhibitor specific to the Kinesin-5 family of
      motor proteins, was used to examine the functional roles of Kinesin-5 proteins
      during the first, asymmetric cell division cycle in the brown alga Silvetia
      compressa. RESULTS: Monastrol treatment had no effect on developing zygotes prior
      to entry into mitosis. After mitosis entry, monastrol treatment led to formation
      of monasters and cell cycle arrest in a dose dependent fashion. These findings
      indicate that Kinesin-5 motors maintain spindle bipolarity, and are consistent
      with reports in animal cells. At low drug concentrations that permitted cell
      division, spindle position was highly displaced from normal, resulting in
      abnormal division planes. Strikingly, application of monastrol also led to
      formation of numerous cytasters throughout the cytoplasm and multipolar spindles,
      uncovering a novel effect of monastrol treatment not observed in animal cells.
      CONCLUSION: We postulate that monastrol treatment causes spindle poles to break
      apart forming cytasters, some of which capture chromosomes and become
      supernumerary spindle poles. Thus, in addition to maintaining spindle bipolarity,
      Kinesin-5 members in S. compressa likely organize microtubules at spindle poles.
      To our knowledge, this is the first functional characterization of the Kinesin-5
      family in stramenopiles.

PMID- 16945152
TI  - SIV escape mutants in rhesus macaques vaccinated with NEF-derived lipopeptides
      and challenged with pathogenic SIVmac251.
AB  - BACKGROUND: Emergence of viral variants that escape CTL control is a major hurdle
      in HIV vaccination unless such variants affect gene regions that are essential
      for virus replication. Vaccine-induced multispecific CTL could also be able to
      control viral variants replication. To explore these possibilities, we
      extensively characterized CTL responses following vaccination with an epitope
      based lipopeptide vaccine and challenge with pathogenic SIVmac251. The viral
      sequences corresponding to the epitopes present in the vaccine as well as the
      viral loads were then determined in every macaque following SIV inoculation.
      RESULTS: In most cases, the emergence of several viral variants or mutants within
      vaccine CTL epitopes after SIV challenge resulted in increased viral loads except
      for a single macaque, which showed a single escape viral variant within its 6
      vaccine-induced CTL epitopes. CONCLUSION: These findings provide a better
      understanding of the evolution of CD8+ epitope variations after vaccination
      induced CTL expansion and might provide new insight for the development of an
      effective HIV vaccine.

PMID- 16945154
TI  - Avian GIS models signal human risk for West Nile virus in Mississippi.
AB  - BACKGROUND: West Nile virus (WNV) poses a significant health risk for residents
      of Mississippi. Physicians and state health officials are interested in new and
      efficient methods for monitoring disease spread and predicting future outbreaks.
      Geographic Information Systems (GIS) models have the potential to support these
      efforts. Environmental conditions favorable for mosquito habitat were modeled
      using GIS to derive WNV risk maps for Mississippi. Variables important to WNV
      dissemination were selected and classified as static and dynamic. The static
      variables included road density, stream density, slope, and vegetation. The
      dynamic variable represented seasonal water budget and was calculated using
      precipitation and evaporation estimates. Significance tests provided
      deterministic evidence of variable importance to the models. RESULTS: Several
      models were developed to estimate WNV risk including a landscape-base model and
      seasonal climatic sub-models. P-values from t-tests guided variable importance
      ranking. Variables were ranked and weights assigned as follows: road density
      (0.4), stream density (0.3), slope (0.2) and vegetation (0.1). This landscape
      base model was modified by climatic conditions to assess the importance of
      climate to WNV risk. Human case data at the zip code level were used to validate
      modeling results. All models were summarized by zip codes for interpretation and
      model validation. For all models, estimated risk was higher for zip codes with at
      least one human case than for zip codes where no human cases were recorded.
      Overall median measure of risk by zip code indicated that 67% of human cases
      occurred in the high-risk category. CONCLUSION: Modeling results indicated that
      dead bird occurrences are correlated with human WNV risk and can facilitate the
      assessment of environmental variables that contribute to that risk. Each
      variable's importance in GIS-based risk predictions was assigned
      deterministically. Our models indicated non-uniform distribution of risk across
      the state and showed elevated risk in urban and as well as rural areas. Model
      limitations include resolution of human data, zip code aggregation issues, and
      quality/availability of vegetation and stream density layers. Our approach
      verified that WNV risk can be modeled at the state level and can be modified for
      risk predictions of other vector-borne diseases in varied ecological regions.

PMID- 16945153
TI  - Heparin (GAG-hed) inhibits LCR activity of human papillomavirus type 18 by
      decreasing AP1 binding.
AB  - BACKGROUND: High risk HPVs are causative agents of anogenital cancers. Viral E6
      and E7 genes are continuously expressed and are largely responsible for the
      oncogenic activity of these viruses. Transcription of the E6 and E7 genes is
      controlled by the viral Long Control Region (LCR), plus several cellular
      transcription factors including AP1 and the viral protein E2. Within the LCR, the
      binding and activity of the transcription factor AP1 represents a key regulatory
      event in maintaining E6/E7 gene expression and uncontrolled cell proliferation.
      Glycosaminoglycans (GAGs), such as heparin, can inhibit tumour growth; they have
      also shown antiviral effects and inhibition of AP1 transcriptional activity. The
      purpose of this study was to test the heparinoid GAG-hed, as a possible antiviral
      and antitumoral agent in an HPV18 positive HeLa cell line. METHODS: Using in vivo
      and in vitro approaches we tested GAG-hed effects on HeLa tumour cell growth,
      cell proliferation and on the expression of HPV18 E6/E7 oncogenes. GAG-hed
      effects on AP1 binding to HPV18-LCR-DNA were tested by EMSA. RESULTS: We were
      able to record the antitumoral effect of GAG-hed in vivo by using as a model
      tumours induced by injection of HeLa cells into athymic female mice. The
      antiviral effect of GAG-hed resulted in the inhibition of LCR activity and,
      consequently, the inhibition of E6 and E7 transcription. A specific diminishing
      of cell proliferation rates was observed in HeLa but not in HPV-free colorectal
      adenocarcinoma cells. Treated HeLa cells did not undergo apoptosis but the
      percentage of cells in G2/M phase of the cell cycle was increased. We also
      detected that GAG-hed prevents the binding of the transcription factor AP1 to the
      LCR. CONCLUSION: Direct interaction of GAG-hed with the components of the AP1
      complex and subsequent interference with its ability to correctly bind specific
      sites within the viral LCR may contribute to the inhibition of E6/E7
      transcription and cell proliferation. Our data suggest that GAG-hed could have
      antitumoral and antiviral activity mainly by inhibiting AP1 binding to the HPV18
      LCR.

PMID- 16945155
TI  - HIV-1 replication in cell lines harboring INI1/hSNF5 mutations.
AB  - BACKGROUND: INI1/hSNF5 is a cellular protein that directly interacts with HIV-1
      integrase (IN). It is specifically incorporated into HIV-1 virions. A dominant
      negative mutant derived from INI1 inhibits HIV-1 replication. Recent studies
      indicate that INI1 is associated with pre-integration and reverse transcription
      complexes that are formed upon viral entry into the target cells. INI1 also is a
      tumor suppressor, biallelically deleted/mutated in malignant rhabdoid tumors. We
      have utilized cell lines derived from the rhabdoid tumors, MON and STA-WT1, that
      harbor either null or truncating mutations of INI1 respectively, to assess the
      effect of INI1 on HIV-1 replication. RESULTS: We found that while HIV-1 virions
      produced in 293T cells efficiently transduced MON and STA-WT1 cells, HIV-1
      particle production was severely reduced in both of these cells. Reintroduction
      of INI1 into MON and STA-WT1 significantly enhanced the particle production in
      both cell lines. HIV-1 particles produced in MON cells were reduced for
      infectivity, while those produced in STA-WT1 were not. Further analysis indicated
      the presence of INI1 in those virions produced from STA-WT1 but not from those
      produced from MON cells. HIV-1 produced in MON cells were defective for synthesis
      of early and late reverse transcription products in the target cells.
      Furthermore, virions produced in MON cells were defective for exogenous reverse
      transcriptase activity carried out using exogenous template, primer and
      substrate. CONCLUSION: Our results suggest that INI1-deficient cells exhibit
      reduced particle production that can be partly enhanced by re-introduction of
      INI1. Infectivity of HIV-1 produced in some but not all INI1 defective cells, is
      affected and this defect may correlate to the lack of INI1 and/or some other
      proteins in these virions. The block in early events of virion produced from MON
      cells appears to be at the stage of reverse transcription. These studies suggest
      that presence of INI1 or some other host factor in virions and reverse
      transcription complexes may be important for early events of HIV-1 replication.

PMID- 16945156
TI  - Health behaviour modelling for prenatal diagnosis in Australia: a geodemographic
      framework for health service utilisation and policy development.
AB  - BACKGROUND: Despite the wide availability of prenatal screening and diagnosis, a
      number of studies have reported no decrease in the rate of babies born with Down
      syndrome. The objective of this study was to investigate the geodemographic
      characteristics of women who have prenatal diagnosis in Victoria, Australia, by
      applying a novel consumer behaviour modelling technique in the analysis of health
      data. METHODS: A descriptive analysis of data on all prenatal diagnostic tests,
      births (1998 and 2002) and births of babies with Down syndrome (1998 to 2002) was
      undertaken using a Geographic Information System and socioeconomic lifestyle
      segmentation classifications. RESULTS: Most metropolitan women in Victoria have
      average or above State average levels of uptake of prenatal diagnosis. Inner city
      women residing in high socioeconomic lifestyle segments who have high rates of
      prenatal diagnosis spend 20% more on specialist physician's fees when compared to
      those whose rates are average. Rates of prenatal diagnosis are generally low
      amongst women in rural Victoria, with the lowest rates observed in farming
      districts. Reasons for this are likely to be a combination of lack of access to
      services (remoteness) and individual opportunity (lack of transportation, low
      levels of support and income). However, there are additional reasons for low
      uptake rates in farming areas that could not be explained by the behaviour
      modelling. These may relate to women's attitudes and choices. CONCLUSION: A lack
      of statewide geodemographic consistency in uptake of prenatal diagnosis implies
      that there is a need to target health professionals and pregnant women in
      specific areas to ensure there is increased equity of access to services and that
      all pregnant women can make informed choices that are best for them. Equally as
      important is appropriate health service provision for families of children with
      Down syndrome. Our findings show that these potential interventions are
      particularly relevant in rural areas. Classifying data to lifestyle segments
      allowed for practical comparisons of the geodemographic characteristics of women
      having prenatal diagnosis in Australia at a population level. This methodology
      may in future be a feasible and cost-effective tool for service planners and
      policy developers.

PMID- 16945157
TI  - TWEAK/Fn14 interaction regulates RANTES production, BMP-2-induced
      differentiation, and RANKL expression in mouse osteoblastic MC3T3-E1 cells.
AB  - Tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), a member of
      the TNF family, is a multifunctional cytokine that regulates cell growth,
      migration, and survival principally through a TWEAK receptor, fibroblast growth
      factor-inducible 14 (Fn14). However, its physiological roles in bone are largely
      unknown. We herein report various effects of TWEAK on mouse osteoblastic MC3T3-E1
      cells. MC3T3-E1 cells expressed Fn14 and produced RANTES (regulated upon
      activation, healthy T cell expressed and secreted) upon TWEAK stimulation through
      PI3K-Akt, but not nuclear factor-kappaB (NF-kappaB), pathway. In addition, TWEAK
      inhibited bone morphogenetic protein (BMP)-2-induced expression of osteoblast
      differentiation markers such as alkaline phosphatase through mitogen-activated
      protein kinase (MAPK) Erk pathway. Furthermore, TWEAK upregulated RANKL (receptor
      activation of NF-kappaB ligand) expression through MAPK Erk pathway in MC3T3-E1
      cells. All these effects of TWEAK on MC3T3-E1 cells were abolished by mouse Fn14
      Fc chimera. We also found significant TWEAK mRNA or protein expression in
      osteoblast- and osteoclast-lineage cell lines or the mouse bone tissue,
      respectively. Finally, we showed that human osteoblasts expressed Fn14 and
      induced RANTES and RANKL upon TWEAK stimulation. Collectively, TWEAK/Fn14
      interaction regulates RANTES production, BMP-2-induced differentiation, and RANKL
      expression in MC3T3-E1 cells. TWEAK may thus be a novel cytokine that regulates
      several aspects of osteoblast function.

PMID- 16945158
TI  - Pseudomyxoma peritonei--a revisit: report of 2 cases and literature review.
AB  - BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare, chronic, relapsing,
      diagnostically challenging and poorly understood disease characterized by
      disseminated mucinous ascites and peritoneal implants. CASE PRESENTATION: We
      report two cases of PMP that represent the two biological variants of
      disseminated peritoneal adenomucinosis (DPAM)--the benign variant and the
      peritoneal mucinous carcinomatosis (PMCA)--the malignant variant, both of which
      were characterized by multiple relapses and progression of the disease despite
      aggressive management. CONCLUSION: Even with a better understanding and recent
      advances in the management of these cases, PMP remains an enigmatic disease with
      a protracted clinical course characterized by multiple recurrences despite
      surgery and/or chemotherapy. Recognition of PMP as a delayed consequence years
      later should alert all surgeons to be extremely vigilant when treating mucinous
      neoplasms of the appendix, with special care being directed towards adequate
      excision and thorough debridement at the initial diagnosis.

PMID- 16945159
TI  - Post-ERCP bacteremia caused by Alcaligenes xylosoxidans in a patient with
      pancreas cancer.
AB  - Alcaligenes xylosoxidans is an aerobic, motile, oxidase and catalase positive,
      nonfermentative Gram negative bacillus. This bacterium has been isolated from
      intestine of humans and from various hospital or environmental water sources.
      A.xylosoxidans is both waterborne and results from the poor-hygienic conditions
      healthcare workers are in. In this case report, the bacteremia which appeared in
      a patient with pancreas cancer after ERCP was described.

PMID- 16945160
TI  - Hepatitis C virus NS2 and NS3/4A proteins are potent inhibitors of host cell
      cytokine/chemokine gene expression.
AB  - BACKGROUND: Hepatitis C virus (HCV) encodes several proteins that interfere with
      the host cell antiviral response. Previously, the serine protease NS3/4A was
      shown to inhibit IFN-beta gene expression by blocking dsRNA-activated retinoic
      acid-inducible gene I (RIG-I) and Toll-like receptor 3 (TLR3)-mediated signaling
      pathways. RESULTS: In the present work, we systematically studied the effect of
      all HCV proteins on IFN gene expression. NS2 and NS3/4A inhibited IFN gene
      activation. NS3/4A inhibited the Sendai virus-induced expression of multiple IFN
      (IFN-alpha, IFN-beta and IFN-lambda1/IL-29) and chemokine (CCL5, CXCL8 and
      CXCL10) gene promoters. NS2 and NS3/4A, but not its proteolytically inactive form
      NS3/4A-S139A, were found to inhibit promoter activity induced by RIG-I or its
      adaptor protein Cardif (or IPS-1/MAVS/VISA). Both endogenous and transfected
      Cardif were proteolytically cleaved by NS3/4A but not by NS2 indicating different
      mechanisms of inhibition of host cell cytokine production by these HCV encoded
      proteases. Cardif also strongly colocalized with NS3/4A at the mitochondrial
      membrane, implicating the mitochondrial membrane as the site for proteolytic
      cleavage. In many experimental systems, IFN priming dramatically enhances RNA
      virus-induced IFN gene expression; pretreatment of HEK293 cells with IFN-alpha
      strongly enhanced RIG-I expression, but failed to protect Cardif from NS3/4A
      mediated cleavage and failed to restore Sendai virus-induced IFN-beta gene
      expression. CONCLUSION: HCV NS2 and NS3/4A proteins were identified as potent
      inhibitors of cytokine gene expression suggesting an important role for HCV
      proteases in counteracting host cell antiviral response.

PMID- 16945161
TI  - Comparison of the in-vivo muscarinic cholinergic receptor availability in
      patients treated with clozapine and olanzapine.
AB  - Clozapine and olanzapine are two atypical antipsychotics that bind to a broad
      range of receptors in vitro. Our group previously reported on the binding of
      clozapine and olanzapine to muscarinic receptors in vivo. Based on these data, a
      direct comparison of the muscarinic receptor availability in vivo under treatment
      with these atypical antipsychotics was performed. [123I]IQNB SPECT scans were
      obtained in seven subjects treated with a high dose (20 mg) of olanzapine and
      seven subjects treated with a moderate dose (mean 275.0 mg, range 200-450 mg) of
      clozapine. Muscarinic receptor-binding indices were determined for basal ganglia,
      cortex, thalamus and pons. When comparing moderate-dose clozapine with high-dose
      olanzapine, significantly lower muscarinic receptor availability was found for
      clozapine in all four cortical regions of interest. Our results suggest that
      treatment with clozapine results in a stronger blockade of the muscarinic
      cholinergic receptors than with olanzapine. These results are compatible with the
      higher rates of anticholinergic side-effects seen with clozapine in clinical
      practice.

PMID- 16945162
TI  - Quetiapine treatment in an open trial in combat-related post-traumatic stress
      disorder with psychotic features.
AB  - Patients with combat-related post-traumatic stress disorder (PTSD) with psychotic
      features frequently fail to respond to antidepressants. Previous research has
      shown that these patients improve significantly after monotherapy with two
      atypical antipsychotics, olanzapine and risperidone. This study investigated the
      clinical outcome of another atypical antipsychotic, quetiapine, in war veterans
      with combat-related PTSD with psychotic features. Male war veterans (n=53) with
      DSM-IV-diagnosed PTSD with psychotic symptoms completed 8 wk of in-patient
      treatment with quetiapine (25-400 mg/d). The reductions in the total and subscale
      scores on the Clinician-Administered PTSD Scale (CAPS), and the increase in the
      Clinical Global Impression - Improvement Scale (CGI-I) were the primary outcome
      measures, and reductions in the Positive and Negative Syndrome Scale (PANSS) were
      the secondary outcome measures. The CGI - Severity of Illness scale (CGI-S) was
      used to assess the global clinical improvement. Drug-Induced Extrapyramidal
      Symptoms scale recorded adverse effects. Two, 6 and 8 wk treatment with
      quetiapine significantly reduced total and the subscales scores on the CAPS,
      PANSS, and CGI-S scales, in patients with psychotic PTSD. The results indicate
      that 8 wk of monotherapy with quetiapine reduced the majority of the psychotic
      and PTSD symptoms in the patients. Our present and previous data suggest that
      treatment-resistant psychotic PTSD patients may improve after taking atypical
      antipsychotics.

PMID- 16945163
TI  - Cerebral 5-HT2A receptor binding is increased in patients with Tourette's
      syndrome.
AB  - Experimental and clinical data have suggested that abnormalities in the
      serotonergic neurotransmissions in frontal-subcortical circuits are involved in
      Tourette's syndrome. To test the hypothesis that the brain's 5-HT2A receptor
      binding is increased in patients with Tourette's syndrome, PET imaging was
      performed. Twenty adults with Tourette's syndrome and 20 healthy control subjects
      were investigated with PET-[18F]altanserin using a bolus-infusion protocol.
      Regions of interest were delineated automatically on co-registered MRI images,
      and partial volume-corrected binding parameters were extracted from the PET
      images. Comparison between control subjects and Tourette's syndrome patients
      showed increased specific [18F]altanserin binding, not only in the a-priori
      selected brain regions hypothesized to be involved in Tourette's syndrome, but
      also post-hoc analysis showed a global up-regulation when testing for a overall
      difference with a randomization test (p<0.03). Increased 5-HT2A receptor binding
      was found not only in regions closely related to subcortical regions in patients
      with Tourette's syndrome, but also in most other brain regions. Our data suggest
      that the serotonergic transmitter system is pathophysiologically involved in
      Tourette's syndrome and that a clinical trial with 5-HT2A receptor antagonists
      may be justified.

PMID- 16945164
TI  - The potential role of gene profiling in the management of early-stage colon
      cancer.

PMID- 16945165
TI  - Highlights from the 42nd Annual Meeting of the American Society of Clinical
      Oncology, Atlanta, GA, June 2006.

PMID- 16945166
TI  - Oxaliplatin-associated hypersensitivity reactions: clinical presentation and
      management.
AB  - Hypersensitivity reactions to cisplatin and carboplatin have been reported in the
      literature to occur at a rate of 10%-27%. Initial reports of hypersensitivity
      reactions to oxaliplatin were low; however, more recently, it appears as if the
      incidence of hypersensitivity reactions to oxaliplatin is similar to that of the
      earlier generation platinum agents. The degree of the reaction varies from mild
      flushing to life-threatening anaphylactic responses. After a mild
      hypersensitivity reaction to oxaliplatin, re-exposing a patient can be considered
      after administering immunosuppressants (eg, high-dose corticosteroids and
      histamine antagonists) and/or prolonging the duration of oxaliplatin infusion. In
      the case of moderate-to-severe reactions to oxaliplatin, re-exposure is usually
      not considered, and alternative forms of therapy should be explored. However,
      there are reports of successful desensitization to oxaliplatin, and therefore, re
      exposing a patient can be considered after carefully weighing the risks and
      benefits of additional oxaliplatin therapy.

PMID- 16945167
TI  - Role of panitumumab in the management of metastatic colorectal cancer.
AB  - Panitumumab (formerly known as ABX-EGF) is the first fully human monoclonal
      antibody directed against the epidermal growth factor receptor in clinical use.
      It has proven to be very well tolerated alone and in combination with other
      cytotoxic chemotherapeutic agents. Panitumumab has demonstrated efficacy as
      monotherapy and with standard chemotherapeutic agents in a wide variety of cancer
      types, including non-small-cell lung cancer, renal, and colorectal cancer (CRC).
      To date, no human antihuman antibodies have been detected, and unlike cetuximab,
      infusion reactions are infrequent, and no premedications are required when
      administering panitumumab. The only significant toxicity has been a rash similar
      to that seen with other agents targeting the epidermal growth factor receptor,
      and such reactions have been predominantly mild to moderate. In metastatic CRC,
      panitumumab has been safe and efficacious when given with other commonly used
      agents in this disease, including irinotecan and fluorouracil. Current studies
      under way are looking at panitumumab in combination with FOLFOX
      (fluorouracil/leucovorin/oxaliplatin) plus bevacizumab as well as with novel
      agents that have yet to come into common clinical practice. Recent progress in
      development of panitumumab in the management of CRC is reviewed, and management
      of associated rash is discussed herein.

PMID- 16945168
TI  - Isolation and characterization of circulating tumor cells in patients with
      metastatic colorectal cancer.
AB  - PURPOSE: Development of targeted therapeutic agents in colorectal cancer (CRC) is
      impeded by the lack of a noninvasive surrogate of drug effect. This pilot study
      evaluated the ability of immunomagnetic separation to isolate circulating tumor
      cells (CTCs) and of the fluorescent microscope system and flow cytometry to
      enumerate and characterize CTCs from patients with metastatic CRC. PATIENTS AND
      METHODS: Fifty patients with metastatic CRC contributed 50 mL of blood at
      treatment initiation and disease evaluation timepoints. Fresh tumor specimens
      were obtained from 17 patients for comparison of circulating and in situ tumor
      cell characteristics. Epithelial cells were magnetically isolated from whole
      blood targeting the antiepithelial cell adhesion molecule (EpCAM). Circulating
      tumor cells were defined as EpCAM isolated, cytokeratin positive, nuclear stain
      positive, and CD45 negative. Total RNA was isolated from EpCAM-enriched CTCs and
      multigene reverse-transcriptase polymerase chain reaction analyses were
      performed. RESULTS: The median number of CTCs detected by flow cytometry was
      2/7.5 mL blood. Mean change in cell count was significantly different for
      patients with tumor progression versus nonprogression (+6.7 vs. +0.2/7.5 mL; P =
      0.001). A correlation was noted between mean fluorescence intensity (flow
      cytometry) of cytokeratin in CTC and matched tumor specimens (r = 0.79, P =
      0.06). Nearly 80% (15 of 19) of samples with >or= 2 CTCs expressed >or= 1
      epithelial marker gene (CK19, CK20, carcinoembryonic antigen, or epidermal growth
      factor receptor). CONCLUSION: Isolating and characterizing CTCs from patients
      with metastatic CRC is feasible. Change in the CTC number might reflect clinical
      status, and flow cytometric and gene expression data suggest similarity of
      circulating and in situ tumor cells. Further evaluation of CTCs for
      pharmacodynamic and clinical monitoring in patients with CRC is warranted.

PMID- 16945169
TI  - Randomized clinical trial of high-dose levamisole combined with 5-fluorouracil
      and leucovorin as surgical adjuvant therapy for high-risk colon cancer.
AB  - BACKGROUND: Levamisole combined with 5-fluorouracil (5-FU) was previously shown
      to significantly reduce tumor relapses and improve patient survival when given
      postoperatively in patients with resected stage III colon cancer. Laboratory
      investigations subsequently documented a direct dose-dependent enhancement of 5
      FU cytotoxicity with increasing concentrations of levamisole against human cancer
      cell lines. A clinical trial was designed to test the value of levamisole given
      at its maximum tolerated dose in combination with 5-FU-based chemotherapy.
      PATIENTS AND METHODS: Eight hundred seventy-eight patients who had undergone
      complete surgical resection of high-risk stage II/III colon cancer were
      stratified by known prognostic factors and randomized to receive 1 of 2 treatment
      regimens: standard-dose levamisole combined with 5-FU and leucovorin; or high
      dose levamisole combined with the same chemotherapy. Serum neopterin was
      monitored in a cohort of patients to evaluate immune function. RESULTS: Severe
      vomiting and neurologic side effects required reduction in the dose of levamisole
      that could be safely administered on the high-dose levamisole regimen. There were
      no significant differences in disease-free survival, overall survival, or levels
      of serum neopterin between the treatment regimens. CONCLUSION: It was not
      possible to improve the efficacy of surgical adjuvant chemotherapy for patients
      with high-risk colon cancer by giving levamisole at its maximum tolerated dose in
      combination with 5-FU and leucovorin. High rates of severe gastrointestinal and
      neurologic side effects were observed with the high-dose levamisole regimen.

PMID- 16945170
TI  - Diverticular disease in patients with colon cancer: subgroup analysis of national
      surgical adjuvant breast and bowel project protocol C-06.
AB  - BACKGROUND: Similar epidemiologic characteristics suggest a common etiology for
      colon cancer (CC) and diverticular disease of the colon (DD). The relationship
      between the 2 diseases is still unclear, and the impact of DD in patients
      diagnosed with CC on disease-free survival (DFS) and overall survival (OS) is
      unknown. National Surgical Adjuvant Breast and Bowel Project (NASBP) protocol C
      06 is a clinical trial comparing oral uracil/tegafur/leucovorin with 5
      fluorouracil/leucovorin in patients with resected stage II/III carcinoma of the
      colon. PATIENTS AND METHODS: The NASBP enrolled 1,608 patients who had undergone
      potentially curative resection for stage II/III colon cancer from 256 medical
      sites between February 14, 1997, and March 31, 1999. RESULTS: Pathology reports
      from 1561 eligible patients retrospectively reviewed for the presence of DD
      revealed that 160 (10.2%) had this disease. The median ages of patients with CC
      and DD and without DD were 67 and 61 years, respectively (P < 0.05). The majority
      of patients were white, and Hispanic patients were better represented in the
      group with DD (P < 0.05). Colon cancer was located in the rectosigmoid in 46.88%
      of patients with DD and in 31.92% of patients without DD (P < 0.05). A baseline
      diagnosis of DD made no significant contribution to DFS or OS without adjustment
      for confoundin factors (P = 0.2 and P = 0.32, respectively) or adjusted for Dukes
      classification and age (P = 0.49 and P = 0.68, respectively). CONCLUSION: The
      prevalence of DD in patients diagnosed and treated for CC was 10.2%. Patients
      with CC with and without DD differed from each other with respect to age, tumor
      location, and ethnicity. There was no negative impact of having DD on DFS and OS
      in patients treated for stage II/III CC.

PMID- 16945171
TI  - Addition of gabapentin to a modified FOLFOX regimen does not reduce oxaliplatin
      induced neurotoxicity.
AB  - BACKGROUND: Sensory neurotoxicity is dose limiting for oxaliplatin, an effective
      drug in the treatment of colorectal cancer (CRC) and other malignancies. This
      study assessed the impact of gabapentin on oxaliplatin dose intensity and
      neurotoxicity. PATIENTS AND METHODS: Patients with previously untreated
      metastatic CRC were recruited sequentially to 2 cohorts: the first used a
      modified FOLFOX6 (fluorouracil/leucovorin/oxaliplatin) regimen alone with
      oxaliplatin 100 mg/m(2) every 2 weeks (mFOLFOX; n = 40), and the second included
      the addition of gabapentin (mFOLFOX+G; n = 41). Gabapentin commenced at 300 mg
      daily, increasing to a maximum of 600 mg 3 times daily to decrease neurotoxicity.
      RESULTS: Doses of gabapentin were increased in 31 of 41 patients, with 39% of
      patients receiving >or= 900 mg daily. The median relative dose intensity of
      oxaliplatin and requirement for dose reductions or delays because of
      neurotoxicity were similar in the 2 cohorts. There was no grade 4 neurotoxicity.
      Whereas grade 3 neurotoxicity was observed in 10% of patients treated with
      gabapentin versus 21% of patients treated with mFOLFOX alone, there was no
      statistically significant difference in the severity of neurotoxicity between the
      2 cohorts (P = 0.89) or the time to recover from grade 2/3 neurotoxicity (P =
      0.97). There were also no significant differences in nonneurologic toxicity or
      antitumor efficacy between the 2 cohorts. CONCLUSION: This study does not support
      a role for gabapentin in reducing the incidence or severity of oxaliplatin
      induced sensory neurotoxicity.

PMID- 16945172
TI  - Cetuximab-induced hypomagnesemia in patients with colorectal cancer.
AB  - BACKGROUND: Cetuximab treatment has been associated with severe hypomagnesemia,
      but the predisposing factors and management of this toxicity have been poorly
      characterized. PATIENTS AND METHODS: The charts of 114 patients with colorectal
      cancer treated with cetuximab were reviewed. Forty-eight evaluable patients had
      normal magnesium levels before initiation of cetuximab and >or=1 repeat magnesium
      level during cetuximab treatment. The incidence, grade, and management of
      hypomagnesemia were described in the evaluable population. RESULTS: Among the
      evaluable population, 13 patients developed grade 3/4 hypomagnesemia (27%). The
      incidence of grade 3/4 hypomagnesemia was 6%, 23%, and 47% in patients receiving
      < 3 months, 3-6 months, and > 6 months of cetuximab therapy, respectively. Grade
      3/4 hypomagnesemia was refractory to oral supplementation and required daily to 3
      times-weekly intravenous magnesium sulfate supplementation at 6-10 g per dose.
      Recovery or amelioration in hypomagnesemia occurred approximately 4 weeks after
      cetuximab discontinuation. CONCLUSION: Severe hypomagnesemia is a frequent side
      effect of cetuximab therapy. Treatment of hypomagnesemia requires frequent
      intravenous magnesium supplementation and can be associated with significant
      patient inconvenience and an increased risk of venous access-related
      complications. Intermittent cetuximab schedules need to be investigated in order
      to reduce the frequency and severity of hypomagnesemia.

PMID- 16945173
TI  - Pharmacological utility of melatonin in the treatment of septic shock:
      experimental and clinical evidence.
AB  - Sepsis is a major cause of mortality in critically ill patients and develops as a
      result of the host response to infection. In recent years, important advances
      have been made in understanding the pathophysiology and treatment of sepsis.
      Mitochondria play a central role in the intracellular events associated with
      inflammation and septic shock. One of the current hypotheses for the molecular
      mechanisms of sepsis is that the enhanced nitric oxide (NO) production by
      mitochondrial nitric oxide synthase (mtNOS) leads to excessive peroxynitrite
      (ONOO-) production and protein nitration, impairing mitochondrial function.
      Despite the advances in understanding of its pathophysiology, therapy for septic
      shock remains largely symptomatic and supportive. Melatonin has well documented
      protective effects against the symptoms of severe sepsis/shock in both animals
      and in humans; its use for this condition significantly improves survival.
      Melatonin administration counteracts mtNOS induction and respiratory chain
      failure, restores cellular and mitochondrial redox status, and reduces
      proinflammatory cytokines. Melatonin clearly prevents multiple organ failure,
      circulatory failure, and mitochondrial damage in experimental sepsis, and reduces
      lipid peroxidation, indices of inflammation and mortality in septic human
      newborns. Considering these effects of melatonin and its virtual absence of
      toxicity, the use of melatonin (along with conventional therapy) to preserve
      mitochondrial bioenergetics as well as to limit inflammatory responses and
      oxidative damage should be seriously considered as a treatment option in both
      septic newborn and adult patients. This review summarizes the data that provides
      a rationale for using melatonin in septic shock patients.

PMID- 16945174
TI  - Permeation of bioactive constituents from Arnica montana preparations through
      human skin in-vitro.
AB  - This study investigated and characterised transdermal permeation of bioactive
      agents from a topically applied Arnica montana tincture. Permeation experiments
      conducted over 48 h used polydimethylsiloxane (silastic) and human epidermal
      membranes mounted in Franz-type diffusion cells with a methanol-water (50:50 v/v)
      receptor fluid. A commercially available tincture of A. montana L. derived from
      dried Spanish flower heads was a donor solution. Further donor solutions prepared
      from this stock tincture concentrated the tincture constituents 1, 2 and 10 fold
      and its sesquiterpene lactones 10 fold. Permeants were assayed using a high
      performance liquid chromatography method. Five components permeated through
      silastic membranes providing peaks with relative retention factors to an internal
      standard (santonin) of 0.28, 1.18, 1.45, 1.98 and 2.76, respectively. No permeant
      was detected within 12 h of applying the Arnica tincture onto human epidermal
      membranes. However, after 12 h, the first two of these components were detected.
      These were shown by Zimmermann reagent reaction to be sesquiterpene lactones and
      liquid chromatography/diode array detection/mass spectrometry indicated that
      these two permeants were 11,13-dihydrohelenalin (DH) analogues (methacrylate and
      tiglate esters). The same two components were also detected within 3 h of topical
      application of the 10-fold concentrated tincture and the concentrated
      sesquiterpene lactone extract.

PMID- 16945175
TI  - Nanoparticles of 5-fluorouracil (5-FU) loaded N-succinyl-chitosan (Suc-Chi) for
      cancer chemotherapy: preparation, characterization--in-vitro drug release and
      anti-tumour activity.
AB  - N-Succinyl-chitosan has favourable properties as a drug carrier, such as
      biocompatibility, low toxicity and long-term retention in the body. It is a good
      candidate for cancer chemotherapy as a polymeric drug carrier. This study
      describes the preparation and characterization of 5-fluorouracil-loaded N
      succinyl-chitosan nanoparticles (5-FU-Suc-Chi/NP) by an emulsification solvent
      diffusion method. The influence of the initial 5-FU concentration on the
      nanoparticle characteristics and release behaviour in phosphate-buffered saline
      solution (PBS) was evaluated. The Suc-Chi nanoparticles had a particle diameter
      (Z-average) in the range 202 approximately 273 nm and a negative zeta-potential
      (approx. -27 to -18 mV). The formulation with an initial 5-FU concentration of
      1000 microg mL-1 provided the highest loading capacity (19%) and the highest
      extent of release (61% at 24 h). The 5-FU-Suc-Chi/NP showed good anti-tumour
      activity against Sarcoma 180 solid tumour and mild toxicity. According to the
      data obtained, this Suc-Chi-based nanotechnology opens new and interesting
      perspectives for cancer chemotherapy.

PMID- 16945176
TI  - Preparation and evaluation of self-microemulsifying drug delivery systems
      (SMEDDS) containing atorvastatin.
AB  - Atorvastatin is insoluble in aqueous solution and the bioavailability after oral
      administration is low. Self-microemulsifying drug delivery systems (SMEDDS)
      containing atorvastatin have been successfully prepared to improve its
      bioavailability. SMEDDS is a mixture of lipid, surfactant, and cosurfactant,
      which are emulsified in aqueous medium under gentle digestive motility in the
      gastrointestinal tract. Pseudo-ternary phase diagrams composed of various
      excipients were plotted. Droplet size, zeta-potential and long-term physical
      stability of the formulations were investigated. The release of atorvastatin from
      SMEDDS capsules was studied using the dialysis bag method in 0.1 M HCl and
      phosphate buffer (pH 7.4), compared with the release of atorvastatin from a
      conventional tablet. A pharmacokinetic study was performed in 6 beagle dogs after
      oral administration of 6 mg kg-1 atorvastatin. The bioavailability of
      atorvastatin SMEDDS capsules was significantly increased compared with that of
      the conventional tablet. SMEDDS capsules consisting of Labrafil, propylene glycol
      and Cremophor RH40 provided the greatest bioavailability. Our studies indicate
      that the use of SMEDDS for the delivery of atorvastatin can improve its
      bioavailability.

PMID- 16945177
TI  - Effect of plasma lipid on pharmacokinetics of ciclosporin and its relationship
      with plasma prednisolone level in renal transplant patients.
AB  - Ciclosporin (cyclosporine A, CyA) is a potent immunosuppressant used after organ
      transplantation. The pharmacokinetic properties of CyA vary widely and
      lipoproteins are the major complexing constituents for CyA in the plasma.
      Therefore, a change in lipoprotein level may influence the pharmacokinetic
      properties of CyA. Prednisolone (PSL) is concomitantly used with CyA as an
      immunosuppressant. After organ transplantation, hyperlipidaemia resulting from
      PSL therapy has been mostly observed and PSL increased the plasma lipoprotein
      level. Therefore, in this study, to obtain more useful information of the
      therapeutic drug monitoring (TDM) of CyA, the relationship between the plasma PSL
      level, plasma lipoprotein level and blood CyA level was investigated in detail.
      An open-label, non-randomized, retrospective study was performed. Data from 21
      male and 11 female patients (age 11-65 years) who received a living-related renal
      transplantation from 2002 to 2004 were included. On postoperative days (PODs) 7,
      14 and 28, the area under the plasma concentration-time curve until 9 h after 40
      mg of PSL administration (AUCPSL40(0-9)) correlated well with total cholesterol
      (T-cho) (r=0.558, 0.768, 0.660, all P<0.05) and high-density lipoprotein (HDL)
      (r=0.688, P<0.05; 0.835, P<0.01; 0.508, p<0.05), and correlated negatively with
      very-low-density lipoprotein (VLDL) (r=-0.486, p<0.01; -0.776, p<0.01; -0.967,
      p<0.01). In addition, AUC until 9 h after CyA administration (AUCCyA0-9) also
      correlated with T-cho (r=0.797, p<0.01; 0.577, p<0.05; 0.901, p<0.01), HDL
      (r=0.514, p<0.05; 0.614, p<0.05; 0.893, p<0.01) and low-density lipoprotein (LDL)
      (r=0.906, p<0.01; 0.573, p<0.05; 0.537, p<0.05), and there was a negative
      correlation with VLDL (r=-0.480, -0.630, -0.632, all p<0.05). Moreover, AUCCyA0-9
      correlated well with AUCPSL40(0-9) (r=0.728, p<0.01; 0.482, p<0.05; 0.688,
      p<0.05); namely, it was considered that the variety of plasma PSL concentrations
      influenced the pharmacokinetic properties of CyA through the change in
      lipoprotein levels. These results suggested that monitoring of the biochemical
      parameters of the plasma lipid and plasma PSL level might be useful for the TDM
      of CyA.

PMID- 16945178
TI  - Site-specific accumulation of the cancer preventive dietary polyphenol ellagic
      acid in epithelial cells of the aerodigestive tract.
AB  - Ellagic acid (EA), a polyphenol present in berries, has been demonstrated to
      prevent oesophageal and colon cancer in animals. To better understand the site
      specificity of these effects, we studied the accumulation and transport of
      [14C]EA in rat aerodigestive epithelial cells in-vivo and in cultured human
      cells. When [14C]EA was administered to rats by gavage, a high content of EA was
      found in the oesophagus and small intestine at 0.5 h after oral administration
      and in the colon at 12 h, with very low amounts in plasma and peripheral tissues.
      Studies in human intestinal Caco-2 and human oesophageal HET-1A cells found very
      limited transcellular transport (Caco-2) of EA but high accumulation (Caco-2 and
      HET-1A) in the cells. In more detailed studies in the Caco-2 cells, accumulation
      of EA displayed ATP- and Na+-dependency. Multiple interventions permitted the
      exclusion of a number of transporters as mediators of this uptake. A dramatically
      reduced transport of EA at low pH (5.5) compared with high pH (7.4) suggested an
      important role for the negative charge of EA. This was supported by the organic
      anion transport inhibitors 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid and
      bromosulfophthalein. The latter produced as much as 78% inhibition at the 100
      microM concentration. Finally, Caco-2 cells were shown to express organic anion
      transporter 4 (OAT4) mRNA, as was the human large intestine. EA appears to be
      accumulated along the aerodigestive tract using OAT-like transporters, one of
      which might be OAT4.

PMID- 16945179
TI  - Plasma profiles of lycopene after single oral and intravenous administrations in
      dogs.
AB  - The objectives of this study were to identify the factors limiting the absorption
      of purified lycopene after oral administration, and to comparatively assess
      plasma data sets after single oral and intravenous administrations in dogs to
      define the conditions for performing an absolute bioavailability study.
      Solubility of purified lycopene (all-trans, 93.5%) was determined in media
      simulating the conditions in the fasted and in the fed upper gastrointestinal
      lumen. After evaluating the plasma levels achieved following single
      administrations of purified lycopene powder to fasted and fed dogs at escalating
      doses (75-750 mg), a crossover study was performed in four fed female mongrel
      dogs at two phases. In phase I, one soft gelatine capsule (10 mg lycopene) with
      500 mL milk was administered orally. In phase II, 500 mL milk was administered
      orally and 250 mL 5% dextrose containing 5 mg lycopene in the form of a binary
      system with hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) was administered
      intravenously over 3.5 h. In-vitro and preliminary canine studies confirmed that,
      after oral administration of lycopene in solid form, arrival of lycopene into the
      systemic circulation was limited by lymphatic transport and, in addition, if the
      administered dose was higher than approximately 2 mg, by intralumenal solubility.
      During the first 50 h after single administrations to fed dogs, lycopene plasma
      levels were lower after intravenous than after oral administration. This could
      have been related to capacity limited elimination of lycopene and/or route
      dependent disposition kinetics. Estimation of the amount of lycopene reaching the
      systemic circulation after oral and after intravenous administration requires
      separate estimations of total body clearance of lycopene.

PMID- 16945180
TI  - Uptake of dexamethasone incorporated into liposomes by macrophages and foam cells
      and its inhibitory effect on cellular cholesterol ester accumulation.
AB  - To confirm the efficacy of dexamethasone incorporated into liposomes in the
      treatment of atherosclerosis, the uptake of dexamethasone-liposomes by
      macrophages and foam cells and its inhibitory effect on cellular cholesterol
      ester accumulation in these cells were investigated in-vitro. Dexamethasone
      liposomes were prepared with egg yolk phosphatidylcholine, cholesterol and
      dicetylphosphate in a lipid molar ratio of 7/2/1 by the hydration method. This
      was adjusted to three different particle sizes to clarify the influence of
      particle size on the uptake by the macrophages and foam cells, and the inhibitory
      effect on cellular cholesterol ester accumulation. The distribution of particle
      sizes of dexamethasone-liposomes were 518.7+/-49.5 nm (L500), 202.2+/-23.1 nm
      (L200), and 68.6+/-6.5 nm (L70), respectively. For each size, dexamethasone
      concentration and dexamethasone/lipid molar ratio in dexamethasone-liposome
      suspension were 1 mg dexamethasone mL-1 and 0.134 mol dexamethasone mol-1 total
      lipids, respectively. The zeta potential was approximately -70 mV for all sizes.
      Dexamethasone-liposomes or free dexamethasone were added to the macrophages in
      the presence of oxidized low density lipoprotein (oxLDL) and foam cells, and then
      incubated at 37 degrees C. The uptake amount of dexamethasone by the macrophages
      and foam cells after a 24-h incubation was L500>L200>free dexamethasone>L70. The
      macrophages in the presence of oxLDL and foam cells were incubated with
      dexamethasone-liposomes or free dexamethasone for 24 h at 37 degrees C to
      evaluate the inhibitory effect on the cellular cholesterol ester accumulation.
      The cellular cholesterol ester level in the macrophages treated with oxLDL was
      significantly increased compared with that in macrophages without additives.
      L500, L200 and free dexamethasone significantly inhibited this cholesterol ester
      accumulation. L500, L200 and free dexamethasone also significantly reduced
      cellular cholesterol ester accumulation in foam cells. In addition, the
      relationship between the area under the uptake amount of dexamethasone-time curve
      (AUC) and the inhibition rate of cholesterol ester accumulation in macrophages
      and foam cells was evaluated. The inhibition rate of cholesterol ester
      accumulation (%) was related to the AUC in both types of cell. These results
      suggested that dexamethasone-liposomes would be a useful approach to the
      development of a novel drug delivery system for atherosclerotic therapy.
      Furthermore, the prediction of the inhibitory effect of dexamethasone on cellular
      cholesterol ester accumulation may become possible by using the results of this
      study.

PMID- 16945181
TI  - Enhanced therapeutic potential of naringenin-phospholipid complex in rats.
AB  - Naringenin is a naturally occurring flavanone, possessing a variety of biological
      activity. Due to its rapid elimination, naringenin needs frequent administration
      to maintain an effective plasma concentration. We have evaluated the therapeutic
      potential of naringenin-phospholipid complex under oxidative stress conditions
      compared with free naringenin. Naringenin-phospholipid complex was prepared and
      assessed for antioxidant activity in carbon tetrachloride intoxicated rats at a
      dose level of 100 mg kg-1 (p.o.). Liver function tests were studied by assessing
      serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase,
      serum alkaline phosphatase and total bilirubin. Marker enzymes of liver, namely
      glutathione peroxidase, superoxide dismutase, catalase and thiobarbituric acid
      reactive substances, were measured to evaluate the antioxidant potential at the
      same dose level. The plasma concentration of naringenin was also measured. It was
      observed that the naringenin-phospholipid complex enhanced the antioxidant
      activity of the biomolecule and protected the liver significantly for a longer
      time as compared with free naringenin at the same dose level. Phospholipid
      complex of naringenin produced better antioxidant activity than the free compound
      with a prolonged duration of action, which may be helpful in reducing the fast
      elimination of the molecule from body.

PMID- 16945182
TI  - Voltage-gated Na+ channel ligands and ATP: relative molecular similarity and
      implications for channel function.
AB  - The voltage-gated sodium channel (VGNC) is targeted by naturally occurring
      ligands and drugs of diverse structure. ATP modulates VGNC current in-vitro but
      is given little prominence in models describing channel function. This
      computational study uses superimposition and molecular fitting to investigate
      relative molecular similarity within the structures of ATP and VGNC ligands. A
      motif of 3 linked atoms (C-N-C) in the adenine ring of ATP satisfies the fitting
      of a wide range of anticonvulsant structures. An alternative group (N-C-N)
      provides one fitting motif for the ester and amide groups of local anaesthetic
      drugs; protonated amine and aromatic groups in the same conformers fit to a
      second motif in the adenine ring. Analogous structures from other drug classes
      with VGNC blocking activity give the same molecular fits to ATP. Structures
      fitted to the adenine ring of ATP occlude the intra-molecular space between the
      nucleoside and triphosphate chain in approximation to their established blocking,
      activating or neutral effects on Na+ current. The findings are discussed in terms
      of drug preferences for VGNC states and channel requirements for ATP.

PMID- 16945183
TI  - Indorenate modifies a1-adrenergic and benzodiazepine receptor binding in the rat
      brain: an autoradiography study.
AB  - Indorenate (5-methoxytryptamine-beta-methylcarboxylate) is a 5-HT1A receptor
      agonist that produces antihypertensive, anxiolytic, antidepressant and
      anticonvulsant effects. However, there is evidence suggesting that these effects
      could involve the activation of benzodiazepine (BZD) receptors but not the
      activation of a1-adrenergic receptors. The goal of this study was to analyse the
      effect of indorenate on a1-adrenergic and BZD receptor binding in specific rat
      brain areas by using in-vitro autoradiography. Coronal brain sections from male
      Wistar rats were used for labelling 5-HT1A (3H-8-OH-DPAT, 2 nM), a1-adrenergic
      (3H-prazosin, 2 nM) and BZD (3H-flunitrazepam, 2 nM) receptor binding in the
      presence or absence of indorenate (1 microM). Indorenate totally displaced 3H-8
      OH-DPAT binding in all the brain areas evaluated. It decreased 3H-prazosin
      binding just in the frontal (30%) and sensorimotor (32%) cortices and in the
      thalamus (21%). Additionally, indorenate diminished 3H-flunitrazepam binding only
      in the cingulate (16%) and piriform (18%) cortices as well as in the dorsal raphe
      nucleus (18%). These results confirm that indorenate is a 5-HT1A ligand and
      suggest the possible participation of a1-adrenergic and BZD receptors in its
      pharmacological properties.

PMID- 16945184
TI  - Synthesis and pharmacological investigation of novel 1-substituted-4-(4
      substituted phenyl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones as a new class of
      H1-antihistamine agents.
AB  - A series of novel 1-substituted-4-(4-substituted phenyl)-4H-[1,2,4]triazolo[4,3
      a]quinazolin-5-ones was synthesized by the cyclization of 2-hydrazino-3-(4
      substituted phenyl)-3H-quinazolin-4-one with various one-carbon donors. The
      starting material, 2-hydrazino-3-(4-substituted phenyl)-3H-quinazolin-4-one, was
      synthesized from 4-substituted aniline by a novel innovative route. When tested
      for in-vivo H1-antihistamine activity on conscious guinea-pigs, all the test
      compounds significantly protected the animals against histamine-induced
      bronchospasm. The compound 1-methyl-4-(4-chloro phenyl)-4H-[1,2,4]triazolo[4,3
      a]quinazolin-5-one (VII) was more potent (72.71% protection), and 1-methyl-4-(4
      methoxy phenyl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-one (II) was equipotent
      (71% protection), when compared with the reference standard, chlorpheniramine
      maleate (71% protection). Compounds II and VII showed negligible sedation (5% and
      8% respectively) when compared with chlorpheniramine maleate (25%). Compounds II
      and VII could serve as prototype molecules for further development as a new class
      of H1-antihistamines.

PMID- 16945186
TI  - Anti-inflammatory, analgesic and anti-oedematous effects of Lafoensia pacari
      extract and ellagic acid.
AB  - Lafoensia pacari St. Hil. (Lythraceae) is used in traditional medicine to treat
      inflammation. Previously, we demonstrated the anti-inflammatory effect that the
      ethanolic extract of L. pacari has in Toxocara canis infection (a model of
      systemic eosinophilia). In this study, we tested the anti-inflammatory activity
      of the same L. pacari extract in mice injected intraperitoneally with beta-glucan
      present in fraction 1 (F1) of the Histoplasma capsulatum cell wall (a model of
      acute eosinophilic inflammation). We also determined the anti-oedematous,
      analgesic and anti-pyretic effects of L. pacari extract in carrageenan-induced
      paw oedema, acetic acid writhing and LPS-induced fever, respectively. L. pacari
      extract significantly inhibited leucocyte recruitment into the peritoneal cavity
      induced by beta-glucan. In addition, the L. pacari extract presented significant
      analgesic, anti-oedematous and anti-pyretic effects. Bioassay-guided
      fractionation of the L. pacari extract in the F1 model led us to identify ellagic
      acid. As did the extract, ellagic acid presented anti-inflammatory, anti
      oedematous and analgesic effects. However, ellagic acid had no anti-pyretic
      effect, suggesting that other compounds present in the plant stem are responsible
      for this effect. Nevertheless, our results demonstrate potential therapeutic
      effects of L. pacari extract and ellagic acid, providing new prospects for the
      development of drugs to treat pain, oedema and inflammation.

PMID- 16945185
TI  - Role of four major components in the effect of Si-Ni-San, a traditional Chinese
      prescription, against contact sensitivity in mice.
AB  - Previously, we demonstrated the inhibitory effects of Si-Ni-San, a traditional
      Chinese prescription, on picryl chloride-induced ear contact sensitivity (PCl
      CS). This study aimed to evaluate the role of the four major constituents
      contained in the prescription (saikosaponins, paeoniflorin, naringin and
      glycyrrhizin) in the inhibitory effect. When administered during the induction
      phase, saikosaponin a and glycyrrhizin showed significant inhibitory effects,
      while paeoniflorin and naringin did not. These components in Si-Ni-San also
      inhibited the activation and proliferation of T lymphocytes as well as the
      production of cytokines such as tumour necrosis factor-alpha and interferon-gamma
      to different extents. Saikosaponin a and paeoniflorin dose-dependently reduced
      the splenocyte adhesion to type I collagen, while glycyrrhizin only showed a
      slight tendency. Furthermore, treatment with glycyrrhizin or saikosaponin a,
      rather than paeoniflorin or naringin, moderately inhibited the matrix
      metalloproteinase (MMP)-2 activity of the splenocytes from PCl-CS mice, and the
      combination of all four components showed a strong inhibition against MMP-2.
      Moreover, the components markedly decreased the serum level of nitric oxide in
      PCl-sensitized mice. The results indicated that saikosaponin a and glycyrrhizin
      may be the major contributors in the alleviation effect of Si-Ni-San on contact
      sensitivity, and paeoniflorin and naringin may exhibit a co-operative effect.

PMID- 16945187
TI  - Compounds from rose (Rosa rugosa) flowers with human immunodeficiency virus type
      1 reverse transcriptase inhibitory activity.
AB  - The aqueous extracts and ethanol precipitates of aqueous extracts of 18 medicinal
      herbs traditionally used in China were screened for their ability to inhibit
      human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT) in-vitro.
      Among the samples screened at a concentration of 500 microg mL-1, dried rose
      (Rosa rugosa) flowers showed the strongest inhibition. The ethanol precipitate of
      the aqueous extract of R. rugosa was processed and two components (P1 and P2)
      were obtained after ion exchange chromatography on DEAE-cellulose. Then, P1-a (Mr
      150 kDa) and P1-b (Mr 8 kDa) were isolated from P1 by gel filtration on Sephadex
      G-200. They inhibited the activity of HIV-1 RT with an IC50 of 158 nM and 148.16
      microg mL-1 (18.5 microM), respectively. Further structural analyses revealed
      that P1-a was a polysaccharide-peptide complex, and P1-b was a polymer consisting
      of acteoside and acteoside derivatives identified by Fourier transform infrared
      spectroscopy, nuclear magnetic resonance, assays of carbohydrate and protein
      contents and high-performance liquid chromatography electrospray ionization mass
      spectrometry.

PMID- 16945188
TI  - Cytotoxic activity and cytostatic mechanism of novel 2-arylbenzo[b]furans.
AB  - The aims of this study were to screen cytotoxic compounds from 14 newly
      synthesized 2-arylbenzo[b]furans and explore their mechanisms of action.
      Cytotoxicity was determined by the MTT method. Cell-cycle distribution was
      detected by flow cytometry. Wright-Giemsa staining was performed to demonstrate
      the morphological features of cells in mitotic phase. Polymerization of tubulin
      was detected by tubulin assembly assay, and the cellular microtubule network was
      observed by immunocytochemical study. Among the 14 compounds screened, 4-formyl-2
      (4-hydroxy-3-methoxyphenyl)-5-(2-methoxycarbonyethyl)-7-methoxy-benzo[b]furan
      (ERJT-12) showed significant cytotoxicity. Our results demonstrated that ERJT-12
      exhibited anti-cancer activity in a variety of tumour cell lines with an IC50
      value (concentration resulting in 50% inhibition of cell growth) of 5.75
      approximately 17.29 microM. Cell cycle analysis showed a concentration-dependent
      accumulation of tumour cells in G2/M phase after treatment with ERJT-12. Further
      investigation indicated that ERJT-12 blocked the cell cycle in M phase, with
      separation and dispersion of chromosomes. ERJT-12 inhibited tubulin
      polymerization in-vitro. Changes of the cellular microtubule network caused by
      ERJT-12 were also detected, which were similar to the changes caused by
      colchicine. These results suggested that the anti-cancer activity of ERJT-12 is
      worth further investigation.

PMID- 16945189
TI  - Development and pharmacokinetics of nimodipine-loaded liposomes.
AB  - In order to improve the water solubility of nimodipine and prolong the time of
      the drug in the circulation, nimodipine-loaded liposomes with a small size and
      high entrapment efficiency were prepared by a method that was easy to scale up
      (the modified ethanol injection method). The nimodipine liposome dispersions were
      characterized with respect to particle size distribution, zeta potential and
      entrapment efficiency. Liposomal nimodipine and nimodipine solution were
      intravenously administered to mice as a single dose of 4 mg kg-1. The
      pharmacokinetic parameters of nimodipine changed significantly when encapsulated
      in liposomes. The clearance of nimodipine encapsulated in liposomes was reduced
      and the elimination half-life was prolonged. The ratios of the area under the
      curve values of nimodipine liposomes to nimodipine solution were 1.78 and 1.90 in
      plasma and cerebral tissue, respectively. The drug concentration in cerebral
      tissue and in plasma showed a good linear correlation, which showed that
      liposomes could efficiently deliver nimodipine into brain tissue. These findings
      suggest that intravenous administration of liposomal nimodipine produces higher
      and more stable plasma and cerebral drug concentrations compared with nimodipine
      solution. In conclusion, liposomal nimodipine is a promising alternative to the
      solution preparation.

PMID- 16945194
TI  - Borderline personality disorder features: the role of self-discrepancies and self
      complexity.
AB  - OBJECTIVES: Borderline personality disorder (BPD) involves disordered self
      conceptions, along with dysphoria and anxiety. The present study examined the
      role of actual-ideal (AI) and actual-ought (AO) self-discrepancies, and self
      complexity as predictors of borderline personality features in a student
      population. METHOD: AI and AO self-discrepancy magnitudes across all self-domains
      were assessed, along with self-complexity, idiographically and nomothetically.
      Borderline personality features were assessed using subscales of the Minnesota
      Multiphasic Personality Inventory (MMPI-2). RESULTS: Both AI and AO self
      discrepancies were directly related to BPD personality features, in that those
      with larger self-discrepancies of both types reported more features. Self
      complexity had no direct relationship to BPD personality features; rather, it
      moderated the relationship between AI, but not AO, self-discrepancies and BPD
      personality features. For individuals low in self-complexity, a stronger
      relationship between AI self-discrepancies and BPD personality features existed.
      CONCLUSIONS: This study is novel in its consideration of the impact of features
      of the self-system on BPD personality features. It highlights the important role
      that AO self-discrepancies, and the combined role of AI self-discrepancies and
      self-complexity, have in increasing vulnerability to BPD. The findings suggest
      that different pathways might be involved in the vulnerability to BPD, depending
      on self-discrepancy type and level of self-complexity.

PMID- 16945195
TI  - Two subjective factors as moderators between critical incidents and the
      occurrence of post traumatic stress disorders: adult attachment and perception of
      social support.
AB  - This paper presents the result of a research which investigated the influence of
      the subjective factors 'adult attachment style' and 'perception of social
      support' in the occurrence of post traumatic stress disorders (PTSD) in a
      population of 544 subjects working for a security company and the Belgian Red
      Cross. The analysis of the results suggests that 'adult attachment style' and
      'perception of social support' moderate between a critical incident and the
      occurrence of a PTSD. In other words, these independent variables differentiate
      between individuals who are more, and who are less prone, to suffer from a PTSD
      after having experienced a critical incident. The results of this research shed
      light on subjective risk factors related to PTSD. The findings can also suggest
      guidelines for the treatment of individuals suffering from a PTSD.

PMID- 16945196
TI  - Measuring interrelating within couples: the Couple's Relating to Each Other
      Questionnaires (CREOQ).
AB  - The Couple's Relating to Each Other Questionnaires (CREOQ) are a set of four
      questionnaires for measuring negative forms of interrelating within couples. They
      enable each partner to rate his/her relating to the other and the other's
      relating to him/her. They are based upon the theoretical structure called the
      interpersonal octagon, and each questionnaire has eight scales. They are usually
      accompanied by a brief, single-scale questionnaire called the US (us as a
      couple), by which each partner rates the quality of the relationship. The set of
      questionnaires was administered to 130 English couples from the community, 157
      English couples seeking couple therapy and 89 Dutch community couples. The Dutch
      couples were also invited to rate themselves and their partners according to the
      items of the revised interpersonal checklist (ICL-R). The mean scores for the US
      and for most of the scales of the four CREOQ were significantly higher in the
      couple therapy sample. The internal reliabilities of the Dutch sample were
      generally lower than those of the English sample. Correlations were examined
      between the 10 ICL-R scales and the 8 CREOQ ones. Some agreement emerged, and for
      the ICL-R, there appeared to be one close, one distant, four upper and two lower
      scales.

PMID- 16945197
TI  - Common and specific effects of couples treatment for alcoholism: a test of the
      generic model of psychotherapy.
AB  - The generic model of psychotherapy (Orlinsky & Howard, 1987) eschews the view
      that inputs, processes or outputs associated with treatment exert linear and
      independent effects on outcomes. Variables within these three clusters must be
      viewed both within the context of time and through their interactions with other
      variables within a class. This study illustrates the use of this model by
      identifying common (comprising both traditional relationship factors and shared
      therapy ingredients) and specific factors in cognitive-behavioural (CB) and
      family systems (FS) treatments for alcoholic couples and tracking their
      contributions over two treatment phases - the acute phase, and the follow-up
      phase. While four process variables (therapy type, intensity of treatment, common
      elements and FS-specific procedures) contributed to outcomes during the active
      treatment phase, these variables became more interactive during follow-up.
      Indeed, high levels of both specific interventions of both treatments were
      negatively associated with benefit, if common factors were also frequently used
      during the acute phase. The best effects were obtained when common and specific
      interventions were counterbalanced, one being frequently used and the other being
      infrequently used. Implications for future alcohol treatment and recommendations
      for research on common and specific factors are discussed.

PMID- 16945198
TI  - Brief psychoeducation for people with personality disorder: a pilot study.
AB  - BACKGROUND: The Patients' Charter for Mental Health Services (DOH, 1997) states
      that a patient is entitled to both know and understand his or her diagnosis.
      Despite this, personality disordered clients are not always well informed about
      their disorder. Some will not be told their diagnosis because of concern that to
      do so would damage the therapeutic alliance. OBJECTIVE: To test the hypothesis
      that the therapeutic alliance is not compromised by engaging in a psychoeducation
      programme that informs about personality disorder. DESIGN: Pilot study, pre-post
      design. METHODS: Eighteen forensic in-patients and 16 community out-patients
      separately participated in a 4-session individual programme that focused on
      personality, personality disorder, and their own diagnosis. Understanding of
      these concepts was explored in a brief structured interview. Therapeutic alliance
      was assessed pre- and post-intervention using the Agnew relationship measure.
      RESULTS: For both samples, participation in the intervention resulted in a
      positive change in four of the five measured components of the therapeutic
      alliance. This change was rated more strongly by clients than therapists, and
      reached statistical significance for bond, partnership, and confidence subscales.
      Participants demonstrated improved knowledge of their disorder following the
      intervention, and all but one gave positive feedback. CONCLUSION: These findings
      support the hypothesis and suggest the therapeutic relationship is not impaired
      when a diagnosis of personality disorder is imparted using this psychoeducation
      programme.

PMID- 16945199
TI  - Resolving threats to the therapeutic alliance in cognitive analytic therapy of
      borderline personality disorder: a task analysis.
AB  - BACKGROUND: Alliance ruptures and premature drop out from psychotherapy are very
      common with patients who have a diagnosis of borderline personality disorder,
      limiting the clinical effectiveness of treatment. AIM: To test and refine a model
      of how therapists successfully resolve threats to the therapeutic alliance
      involving enactment of problematic relationship patterns in the cognitive
      analytic therapy of borderline personality disorder. METHOD: Task analysis
      (Greenberg, 1984a) of 107 enactments from 66 sessions in four good outcome cases,
      compared with 35 enactments from 16 sessions in two poor outcome cases. This
      systematically compares a rational model of process with empirically coded
      transcripts of therapy sessions where independent raters have identified an
      alliance threat event. RESULTS: The process stages of the rational model were
      observed, and 20 refinements were made, including a new process stage, heuristic
      principles and 'when-then' steps. Therapists were found to cycle between stages.
      Therapists in good outcome cases recognized the majority of these enactments and
      focused attention to them in contrast to poor outcome cases where therapists
      usually failed to notice or draw attention to the alliance threat and did not
      adhere to the model. CONCLUSION: Competent resolution of alliance-threatening
      events is crucially dependent on therapists' ability to recognize them, and
      secondarily on their adherence to the principles in the refined model. The model
      is consistent with prior research and can be used in supervision and quality
      improvement strategies.

PMID- 16945200
TI  - Engaging hard to engage clients: a Q methodological study involving clinical
      psychologists.
AB  - This research uses Q methodology to collate a number of techniques, and to
      investigate what techniques are used to encourage engagement across a number of
      clinical psychology specialities. Eleven groups of participants from different
      clinical specialities were interviewed in order to develop a set of 51 statements
      reflecting engagement techniques that clinicians felt that they were likely to
      use with 'hard to engage' clients. Seventy-five participants from a similar range
      of specialities were then asked to Q sort these statements and provide other
      demographic information. Forty-four participants returned completed Q sorts which
      were factor analysed by a tailored program (PQ Method) to investigate how the
      statements fall into patterns that reflect ways clinicians approach engagement.
      Varimax rotation produced five factors, four of which were able to be interpreted
      by participant information and comments. These accounts were taken back to some
      of the initial participants for 'reflexive correction' (Stainton Rogers, 1995).
      The four factor patterns are discussed in relation to existing literature and the
      research questions. These identified factors are: (i) the client focused
      approach; (ii) the interpersonal professional; (iii) the 'eclectic' or systemic
      approach; (iv) the expert listener. The implications for training, clinical
      practice and research are discussed.

PMID- 16945201
TI  - Repetitive skin-cutting: parental bonding, personality and gender.
AB  - OBJECTIVES: This study examines (a) the extent to which repetitive skin-cutting
      is most prevalent among women and those with a history of trauma; and (b) among
      those skin-cutters without a history of trauma, the extent to which borderline
      personality disorder (BPD) features as a primary diagnosis and whether disturbed
      parental bonding might be associated with this form of self-harm. METHOD: Details
      of gender and reported experiences of trauma were recorded for a large,
      consecutive sample of skin-cutters (N=517) who attended a general hospital.
      Psychiatric diagnoses and parental bonding instrument (PBI) scores were obtained
      for a subsample of skin-cutters (N=81) and comparison group participants without
      experiences of trauma. RESULTS: No gender differences were observed among skin
      cutters, most of whom reported experiences of trauma. BPD was recorded for a
      minority of those skin-cutters without a history of trauma. PBI scores
      discriminated between non-BPD skin cutters and non-BPD comparison participants
      without a history of trauma. CONCLUSIONS: Although these results provide further
      confirmation of a potential association between prior trauma and repetitive skin
      cutting, they rigorously challenge the validity of reported gender differences
      for this behaviour. Further, this study has identified that repetitive skin
      cutting can arise independently of BPD and prior trauma. Clinical implications of
      these results and suggested directions for future research are discussed.

PMID- 16945202
TI  - The negative as potential prognostic marker of outcome in psychotherapy.
AB  - From 73 patients, 10 with the best, and 10 with the worst outcomes after
      psychotherapy were compared statistically for the frequency of 'not' and 'never'
      at commencement of psychotherapy, and for change in their frequency after
      therapy. A highly statistically significantly difference was found at
      commencement of psychotherapy in that the negative was used more frequently by
      the worst outcome group (p=.006). No significant differences were found for
      change in frequency after therapy. Thus, the frequent use of the negative at
      commencement of psychotherapy seems to predict a poor outcome.

PMID- 16945203
TI  - Working with parentification: implications for clients and counselling
      psychologists.
AB  - This paper concerns the concept of parentification, whereby children take on
      inappropriate parental roles. A brief theoretical overview is presented, showing
      that parentification has important implications for understanding both clients'
      and counselling psychologists' experiences. Specific ways of assessing adult
      clients who were parentified as children are described, focusing on
      parentification criteria and typical profiles. This is followed by a description
      of a deparentifying process, including exploring shame-based experiences,
      resisting splitting and working with projective identification. These discussions
      are illustrated by examples from an anonymized case study of a client who was
      parentified as a child. Finally, the paper includes a discussion of possible
      dilemmas and difficulties that may arise when parentified clients and parentified
      counselling psychologists work together. Although previous literature has
      discussed parentification separately for counselling psychologists and clients,
      this paper is unique in its discussion of the interaction between the client's
      and counselling psychologist's experiences of parentification and the
      corresponding impact on the therapeutic alliance. The paper concludes by
      emphasising the importance of personal therapy and supportive working
      environments for the well-being of counselling psychologists and consequently
      that of their clients.

PMID- 16945208
TI  - Regional cerebral blood flow reductions, heart failure and Alzheimer's disease.
AB  - OBJECTIVES: To discuss whether there are similarities between the functional
      brain abnormalities detectable in association with the diagnoses of heart failure
      (HF) and Alzheimer's disease (AD), focusing particularly on neuroimaging findings
      in vivo. METHODS: Using an electronic database (Medline), we reviewed imaging
      studies that have evaluated resting cerebral blood flow (CBF), resting glucose
      metabolism or amyloid deposition in groups of subjects suffering AD or HF
      compared with healthy controls. RESULTS: Single photon emission computed
      tomography (SPECT) investigations have reported global CBF reductions in HF
      groups compared with controls. In one recent SPECT study using modern voxel-based
      methods for image analysis, regional CBF deficits in the pre-cuneus and posterior
      cingulate gyrus were detected in a sample of HF sufferers relative to controls.
      The regional distribution of functional deficits in the latter study was similar
      to that found in many positron emission tomography (PET) investigations of
      glucose metabolism at early AD stages, as well as in recent PET investigations of
      amyloid deposition in AD. DISCUSSION: Imaging studies have rarely investigated
      whether there are localized functional brain deficits in association with HF.
      Recent regional CBF SPECT data provide preliminary anatomic support to a view
      that AD-like brain changes may develop in HF patients, possibly as a consequence
      of chronic CBF reductions. Additional studies of larger HF samples are needed to
      confirm this possibility, preferably using PET measures that have afforded
      greater sensitivity and specificity to identify brain functional abnormalities
      associated with the diagnosis of AD, such as indices of glucose metabolism and
      amyloid deposition.

PMID- 16945209
TI  - Congestive heart failure and Alzheimer's disease.
AB  - The increase in average life expectancy is resulting in an increasing prevalence
      of major invalidating illnesses, such as cardiovascular disease and dementia.
      Congestive heart failure (CHF) is a chronic, progressive disease representing the
      advanced stage of cardiac illnesses. Cognitive impairment is known to be a
      frequent feature of CHF patients. The epidemiologic pictures of mild cognitive
      impairment (MCI), Alzheimer's disease (AD) and CHF are predicted to worsen with
      the demographic expansion of the elderly population. Nevertheless, there has been
      little structured research on cognitive impairment in patients with CHF. This is
      unfortunate not only because CHF is the leading cause of hospitalization in the
      elderly and a leading cause of disability and death, but also for important
      clinical and socioeconomic implications including those related to comorbidity in
      advanced age and the need to early detect factors which may precipitate the
      conversion of MCI to AD. In this review, several aspects of the role of CHF in
      cognitive impairment are evaluated. Owing to the lack of studies focusing on CHF
      in AD, the pathophysiology of cardiac failure in cognitive impairment is
      addressed in light of possible preventive strategies against the onset of AD.
      These include prevention of oxygen radical and peroxynitrite production,
      supplementation of nitric oxide (NO) donors, as well as the achievement of an
      adequate antioxidant supply, better if obtained with a targeted and
      individualized nutritional approach. A systematic neuropsychologic testing of
      older patients with heart failure is to identify those with early cognitive
      impairment and promptly establish traditional therapies such as angiotensin
      converting enzyme (ACE) inhibitors, digoxin or beta-blockers. The
      neuropsychologic assessment in CHF patients is also fundamental to disclose
      conditions potentially favoring the onset of cognitive impairment such as
      depression. Finally, management schemes should include exercise training programs
      as well as patient and caregiver education.

PMID- 16945210
TI  - Cardiac risk factors and potential treatments in Alzheimer's disease.
AB  - Dementia is one of the commonest neurological disorders in the elderly
      population. In regards to the increasing longevity of populations worldwide,
      prevention of dementia has become a major public health challenge. There has been
      an intense research in the identification of modifiable risk factors for
      dementia. These risk factors could then be used as targets for intervention,
      pharmacologic or non-pharmacologic. Numerous reports of the relation between
      cardiovascular risk factors and cognitive decline and dementia have been
      published over the past years. This review focuses on the cardiovascular risk
      factors hypertension, hyperlipidemia and diabetes mellitus as targets for
      prevention of cognitive decline, overall dementia and Alzheimer's disease.
      Observational studies and clinical trials regarding the association between
      antihypertensive, lipid lowering and antidiabetic medications and the risk of
      impaired cognition, dementia or Alzheimer's disease are reviewed. Based on these
      data, we propose that early interventions at reducing these cardiovascular risk
      factors may have an impact on future incidence and prevalence of cognitive
      deficits of many etiologies including Alzheimer's disease.

PMID- 16945211
TI  - Update on hypertension and Alzheimer's disease.
AB  - Several studies report that blood pressure is increased in victims of Alzheimer's
      disease (AD) decades before the onset of the disease. Years before onset of
      Alzheimer's disease, blood pressure start to decrease and continues to decrease
      during the disease process. High blood pressure has also been related to
      pathological manifestations of Alzheimer's disease (senile plaques,
      neurofibrillary tangles, hippocampal atrophy). The exact mechanism behind these
      associations is not clear. Hypertension is also a risk factor for stroke,
      ischemic white matter lesions, silent infarcts, general atherosclerosis,
      myocardial infarction and cardiovascular diseases, and often clusters with other
      vascular risk factors, including diabetes mellitus, obesity and
      hypercholesterolemia. Also these risk factors have been related to Alzheimer's
      disease. Hypertension may thus cause cerebrovascular disease that may increase
      the possibility for individuals with AD encephalopathy to express a dementia
      syndrome. Hypertension may also lead to vessel wall changes in the brain, leading
      to hypoperfusion, ischemia and hypoxia which may initiate the pathological
      process of AD. Finally, subclinical AD may lead to increased blood pressure, and
      similar biological mechanisms may be involved in the pathogenesis of both
      disorders. Hypertension is a common disorder and often untreated. Several
      observational studies have reported that use of antihypertensives decreases risk
      of AD. Even though hypertension only results in a moderately increased risk of
      AD, or overall dementia, better treatment of hypertension may have an immense
      effect on the total number of demented individuals.

PMID- 16945212
TI  - Cardiovascular disease and risk of Alzheimer's disease.
AB  - Several recent studies demonstrate associations between cardiovascular disease
      and its risk factors and the incidence of Alzheimer's disease. This review will
      examine the evidence for these associations and possible pathogenetic pathways.
      Clinical relevance and implications of these associations will also be discussed.

PMID- 16945213
TI  - Change in circulating C-reactive protein is not associated with atorvastatin
      treatment in Alzheimer's disease.
AB  - Amyloid containing senile plaques (SP) and neurofibrillary tangles (NFT) are
      histologic hallmarks of Alzheimer's disease (AD). Interestingly the SP and NFT
      found in non-demented, age-matched individuals with ischemic heart disease and/or
      hypertension are morphologically and topographically identical to those in AD.
      Cholesterol plays a significant role in production and accumulation of amyloid
      beta (Abeta) and progression of AD. Cholesterol is also a major contributor in
      atherosclerotic changes and cardiovascular disease. Numerous studies acknowledged
      benefits of cholesterol-lowering statins in slowing down the progression of AD,
      improving cognitive status and significantly reducing risk of cardiovascular
      events. Accumulating evidence suggests that there is a chronic inflammatory
      reaction in the areas of the brain affected by AD and C-reactive protein (CRP) is
      identified as a key molecule of acute phase of inflammation. CRP is also a very
      sensitive marker for cardiovascular events and excellent prognostic tool in post
      heart attack and post-coronary artery bypass surgery recovery. Here we report
      that cholesterol lowering with atorvastatin produces no significant change in CRP
      levels in treating AD patients who participated in ADCLT (AD cholesterol lowering
      trial).

PMID- 16945214
TI  - Atrial fibrillation and risk of dementia in non-demented elderly subjects with
      and without mild cognitive impairment.
AB  - OBJECTIVES: Mild cognitive impairment (MCI) is regarded as a precursor to
      dementia, but not all patients with MCI actually develop dementia. As Alzheimer
      and vascular dementia are thought to share many common etiopathogenetic
      mechanisms, we investigated whether the vascular risk factor atrial fibrillation
      affects the risk of conversion to dementia for different MCI subtypes diagnosed
      according to international criteria. METHODS: One hundred and eighty elderly
      outpatients with MCI and 431 elderly outpatients with a normal cognition were
      followed up for a mean of 3 and 4 years, respectively. The risk of conversion to
      dementia associated with atrial fibrillation was studied in both samples using a
      Cox proportional hazards model adjusted for socio-demographic and medical
      variables. RESULTS: Overall conversion rate to dementia was 10.5 (8.0-13.8 per
      100 person-years) in the MCI group and 2.2 (1.5-3.1 per 100 person-years) in the
      normal cognition group. Atrial fibrillation was significantly associated with
      conversion to dementia [hazard ratio (HR): 4.63; 95% confidence interval: 1.72
      12.46] in the MCI group but not in the cognitively normal group (HR: 1.10; 95%
      confidence interval: 0.40-3.03). DISCUSSION: Current diagnostic criteria for MCI
      subtypes define heterogeneous populations, but atrial fibrillation can be useful
      in identifying people with increased risk of conversion to dementia.

PMID- 16945215
TI  - Interventions for heart disease and their effects on Alzheimer's disease.
AB  - OBJECTIVES: To review the contributions of cardiovascular disease to Alzheimer's
      disease and vascular dementia. METHODS: Review of the literature. RESULTS:
      Alzheimer's disease and vascular dementia both share significant risk
      attributable to cardiovascular risk factors. Hypertension and
      hypercholesterolemia at midlife are significant risk factors for both subsequent
      dementia. Diabetes and obesity are also risk factors for dementia. Stressful
      medical procedures, such as coronary artery bypass and graft operations also
      appear to contribute to the risk of Alzheimer's disease. Apolipoprotein E is the
      major risk factor for Alzheimer's disease. Apolipoprotein E does not appear to
      contribute to Alzheimer's disease by increasing serum cholesterol, but it might
      contribute to the disease through a mechanism involving both Abeta and an
      increase in neuronal vulnerability to stress. DISCUSSION: The strong association
      of cardiovascular risk factors with Alzheimer's disease and vascular dementia
      suggest that these diseases share some biologic pathways in common. The
      contribution of cardiovascular disease to Alzheimer's disease and vascular
      dementia suggest that cardiovascular therapies might prove useful in treating or
      preventing dementia. Antihypertensive medications appear to be beneficial in
      preventing vascular dementia. Statins might be beneficial in preventing the
      progression of dementia in subjects with Alzheimer's disease.

PMID- 16945216
TI  - How do heart disease and stroke become risk factors for Alzheimer's disease?
AB  - BACKGROUND: Heart disease and stroke are two of the major leading causes of death
      and disability in the world. Mainly affecting the elderly population, heart
      disease and stroke are important risk factors for Alzheimer's disease (AD).
      METHODS: This review examines the evidence linking chronic brain hypoperfusion
      (CBH) produced by several types of heart disease and stroke on the development of
      AD. RESULTS: The evidence indicates a strong association between such risk
      factors as coronary artery bypass surgery (CABG), atrial fibrillation,
      aortic/mitral valve damage, hypertension, hypotension, congestive heart failure,
      cerebrovascular-carotid atherosclerosis, and transient ischemic attacks in
      producing CBH. In people whose cerebral perfusion is already diminished by their
      advanced age, further cerebral blood flow reductions from heart-brain vascular
      related risk factors, seemingly increases the probability of AD. The evidence
      also suggests that a neuronal energy crisis brought on by a relentless CBH is
      responsible for protein synthesis defects that later result in the classic AD
      neurodegenerative lesions such as the formation of excess beta-amyloid plaques
      and neurofibrillary tangles. CONCLUSIONS: Knowledge of how heart disease and
      stroke can progress to AD should provide a better understanding of the
      physiopathology characteristic of AD and also target more precise therapy in
      preventing, controlling or reversing this dementia.

PMID- 16945217
TI  - Transcranial and extracranial ultrasound assessment of cerebral hemodynamics in
      vascular and Alzheimer's dementia.
AB  - BACKGROUND: Increasing life expectancy of the population leads to a higher
      incidence of dementia. Exact differentiation between the most common types,
      vascular dementia (VD) and Alzheimer's dementia (AD), is crucial to the
      development and application of new treatment strategies. Both conditions are
      thought to differ greatly by their extent of microvascular affection.
      Transcranial and extracranial ultrasound permits analysis of cerebral
      hemodynamics and should help to differentiate between VD and AD. We compare
      multimodal ultrasound data between VD, AD and controls, and give an overview of
      the literature on this topic. METHODS: Twenty VD and 20 AD patients were studied
      and compared with 12 age-matched controls. Transcranial color-coded ultrasound
      was performed to assess blood flow velocity (V(mean)) and pulsatility indices
      (PI) of the middle cerebral artery (MCA). Extracranial duplex and Doppler
      ultrasound techniques were used to assess the blood volume flow (BVF) in the
      anterior circulation (both internal carotid arteries [ICA]) and posterior
      circulation (both vertebral arteries [VA]), the global cerebral blood flow (CBF =
      BVF(ICA) + BVF(VA)), the global cerebral circulation time (CCT = time delay of
      echo-contrast bolus arrival between ICA and internal jugular vein) and global
      cerebral blood volume (CBV = CCT x CBF). RESULTS: MCA V(mean) in VD (36 +/- 8
      cm/s) and AD (43 +/- 13 cm/s) were significantly lower than in controls (59 +/-
      13 cm/s) but did not differ significantly between VD and AD groups. PI (1.1 +/-
      0.2; 1 +/- 0.2; 0.9 +/- 0.2) only differed significantly between VD group and
      controls. CBF and CCT in VD (570 +/- 61 ml/min; 8.8 +/- 2.6 s) and AD (578 +/- 77
      ml/min; 8.2 +/- 1.4 s) were similar but differed significantly from controls (733
      +/- 54 ml/min; 6.4 +/- 0.8 s). BVF in the anterior and posterior circulation of
      VD group (412 +/- 62 and 158 +/- 38 ml/min) and AD group (428 +/- 62 and 150 +/-
      41 ml/min) were significantly lower than in controls (537 +/- 48 and 199 +/- 26
      ml/min) but did not differ significantly between the patient groups. DISCUSSION:
      Transcranial and extracranial ultrasound does not help to distinguish between VD
      and AD. However, our results add insight into the pathophysiology of dementia,
      arguing in favor of a common 'vascular' pathway in both conditions.

PMID- 16945218
TI  - Cerebrovascular disease, APOE epsilon4 allele and cognitive decline in a
      cognitively normal population.
AB  - OBJECTIVES: To investigate whether cerebrovascular disease (CVD) and
      apolipoprotein E (APOE) epsilon4 allele were associated with cognitive decline
      and whether the relationship between CVD and cognitive decline varied by APOE
      epsilon4 status. METHODS: A total of 809 cognitively normal community-dwelling
      residents aged >75 years were followed to detect subjects with cognitive decline,
      defined as follow-up. Mini-mental state examination (MMSE) score was >10% decease
      of the baseline score. Logistic and multinomial logistic models were developed to
      estimate odds ratio (OR) and 95% confidence interval (CI) of cognitive decline
      related to a history of CVD and APOE epsilon4 by taking into account major
      potential confounders including baseline MMSE score. RESULTS: During the mean 3.5
      years of follow-up, 190 subjects experienced cognitive decline. Multi-adjusted
      ORs (95% CIs) of overall cognitive decline were 2.27 (1.23-4.17) for CVD and 1.69
      (1.13-2.54) for APOE epsilon4, but no interaction was detected. Multinomial
      logistic analysis led to the CVD-related ORs of 1.42 (0.75-2.67) for cognitive
      decline without progression to dementia and 3.41 (1.55-7.55) for the decline
      progressing to dementia; similar analysis from a separate model led to adjusted
      OR of 2.28 (0.88-5.87; p=0.09) for the decline progressing to Alzheimer's
      disease. The risk effects of CVD on cognitive decline with progression to
      dementias were statistically significant mainly among individuals without APOE
      epsilon4 allele. CONCLUSIONS: CVD is a major risk factor for cognitive decline
      associated with progression to dementia and Alzheimer's disease. There appears no
      interaction between CVD and APOE epsilon4 on cognitive decline in very old
      people.

PMID- 16945219
TI  - Effects of acidosis on brain capillary endothelial cells and cholinergic neurons:
      relevance to vascular dementia and Alzheimer's disease.
AB  - Alzheimer's disease is a progressive brain disorder which is neuropathologically
      characterized by an increased number of beta-amyloid plaques, tau pathology and
      synapse loss. Recent research suggests that vascular pathology may be also
      important for the development and progression of Alzheimer's disease. It is still
      unknown whether there is a relation between damage of brain capillary endothelial
      cells (BCEC) and subsequent cholinergic cell death. The aim of this study was to
      examine the effects of acidosis on cell death of BCEC and cholinergic neurons in
      an organotypic brain slice model. We show that BCEC were heavily damaged in
      medium at pH<6.6. Cholinergic neurons incubated in medium pH 6.0 degenerated
      within 2-3 days and were not rescued by nerve growth factor (NGF). Lactate did
      not affect the survival of BCEC or cholinergic neurons. Both BCEC and cholinergic
      cells were not affected at pH 7.4, 7.0 or 6.6. It is concluded that both
      endothelial cells and cholinergic neurons have a high capacity to compensate for
      pH changes. At a certain pH, however, the vascular and neuronal cells show the
      same vulnerability, indicating that a low pH is deleterious for the cerebral
      microenvironment. Future studies are necessary to explore whether temporary pH
      changes could be responsible for cerebrovascular damage and cholinergic cell
      death. Acidosis may play an important role in the development of vascular
      dementia and Alzheimer's disease.

PMID- 16945220
TI  - Is the ischemic blood-brain barrier insufficiency responsible for full-blown
      Alzheimer's disease?
AB  - The goal of this paper is to provide scientists with a comprehensive review of
      the state-of-the-art influence the ischemic blood-brain barrier (BBB) has on the
      final development of Alzheimer's disease and to provide detailed food-for-thought
      which will hopefully stimulate more researchers in this area of neuroscience.
      Understanding new and fundamental concepts about the behavior of the BBB during
      long-term reperfusion after ischemia with a variety of new neuropathogenic
      factors can hopefully provide some interesting clues related to the pathologic
      processes issues that have been receiving considerable attention in the human
      clinic. We present the recent data to understand the role of the BBB in
      maturation of both diseases and try to differentiate between primary and
      secondary pathologic mechanisms. In conclusion, the neuropathogenesis of
      Alzheimer's disease involves an initial ischemic neuronal alterations leading to
      enhanced neuronal vulnerability to beta-amyloid peptide and the ischemic
      breakdown of the BBB with leakage of serum borne beta-amyloid peptide into brain
      parenchyma, activation of beta-amyloid peptide-dependent toxicity culminating in
      the formation of amyloid plaques and finally end in full-blown Alzheimer's
      disease. In summary, probably we have combined mechanism(s) of ischemia
      processes, ischemic and chronic BBB dysfunction and beta-amyloid peptide
      dependent injury in pathology of neurodegeneration that is observed in
      Alzheimer's disease. We speculate that Alzheimer's disease may be caused by
      silent and sublethal ischemic episodes that attack and slowly steal the minds of
      its victims. Finally, our review proposes the ischemic BBB-dependent mechanism(s)
      that probably are responsible for full-blown Alzheimer's disease.

PMID- 16945221
TI  - Interaction of cardiovascular disease and neurodegeneration: transcranial Doppler
      ultrasonography and Alzheimer's disease.
AB  - OBJECTIVE: Recent post-mortem studies have reported that the severity of
      atheromatous deposits in the circle of Willis is significantly greater, relative
      to non-demented (ND) elderly persons, in subjects with neuropathologically
      diagnosed Alzheimer's disease (AD). Additionally, the severity of intracranial
      atherosclerosis correlates significantly with the densities of neuritic plaques
      and neurofibrillary tangles. In this study, we examine the arteries of the circle
      of Willis by transcranial Doppler (TCD) ultrasonography. METHODS: TCD was used to
      measure, in 25 AD patients and 30 ND elderly subjects, mean flow velocities and
      pulsatility indices in 16 different segments of the circle of Willis. The data
      were compared with and without adjustment for age, gender and systolic blood
      pressure. RESULTS: The AD patients had systematically higher pulsatility indices
      (p<0.005) than the ND group. Incremental increases of pulsatility indices in
      these segments had odds ratios ranging from 1.8 to 48 for the presence of AD when
      adjusted for age, gender and systolic blood pressure. The left internal carotid
      artery siphon and the left posterior cerebral artery were the two vessels that
      were strongly associated with AD diagnosis. Mean flow velocities were generally
      lower in patients with AD but the differences did not reach the significance
      level. DISCUSSION: The pulsatility indices of the arteries of AD patients were
      generally greater than those of similarly-aged ND subjects. This difference is
      most likely due to increased arterial wall rigidity imposed by atherosclerotic
      changes. Atherosclerotic disease of intracranial arteries may be a risk factor
      for AD.

PMID- 16945222
TI  - Paradoxical embolization: a potential cause of cerebral damage in Alzheimer's
      disease?
AB  - BACKGROUND: There are considerable overlaps between vascular dementia and
      Alzheimer's disease (AD), with a suggestion that cerebrovascular disease (CVD)
      contributes to the neurodegenerative pathology of AD. Paradoxical embolization of
      venous emboli into the systemic circulation through a venous to arterial
      circulation shunt (v-aCS), the most commonly a patent foramen ovale (PFO), is
      known to cause cryptogenic stroke in younger people. We reviewed the potential
      role of paradoxical embolization in AD. METHODS: A review of the literature on
      paradoxical embolization in neurological disorders and techniques to detect v-aCS
      and PFO, supplemented by data from our own studies. RESULTS: Before our research,
      the role of paradoxical embolism in dementia had not been studied. The potential
      role of embolization in cerebral damage was highlighted by studies in patients
      undergoing coronary artery bypass or carotid surgery. Paradoxical embolization
      was found to occur in patients with cryptogenic stroke, migraine, decompression
      sickles and during hip surgery. The methods for detecting v-aCS or PFO had not
      been standardized. We found 'significant' v-aCS (equivalent to PFO) in 32% of AD
      patients compared with 22% of controls, but the study was not sufficiently
      powered to test the statistic significance of this difference. In AD, there was
      evidence of an association between 'significant' v-aCS and the severity of white
      matter hyperintensities on magnetic resonance imaging (MRI). CONCLUSION:
      Paradoxical embolization through a v-aCS may be a potentially preventable or
      treatable cause of CVD in AD.

PMID- 16945223
TI  - [Evaluation of the quality of nursing care: qualitative and quantitative analysis
      on a sample of nursing documents].
AB  - The theory of continuous quality improvement is related to the principles of
      Total Quality and focuses on three main elements: client satisfaction, erogation
      of services and the informative system. In this wide context, the experience of
      the Niguarda Ca Granda Hospital regarding the introduction of certified nursing
      documents is described. The aspects considered are the introduction and
      management of the document, also taking into consideration the strategies adopted
      for modifying professional behaviour such as training. The evaluation confirms
      that any project aimed at improving the quality of care can be achieved as long
      as the Hospital management make a strategic decision and there is involvement of
      the individual professionals.

PMID- 16945224
TI  - [Teaching nursing research at bachelor and second level degree: opinions of
      nursing associate professors and nursing researchers].
AB  - Nursing research is a systematic and very important enquiry for improving
      clients' quality of life and effective and efficient nursing care. National and
      international literature state that all nurses should have knowledge and
      responsibilities in research which are different in relation to their educational
      level. The aim of the present study was to collect opinions of the new professors
      in nursing about objectives, contents and methods for teaching nursing research
      at Bachelor and Master Degree. The sample was made of nine participants who were
      interviewed by twenty questions sent by e-mail. The interviews were analysed
      using quantitative-descriptive and qualitative-phenomenological methods
      (triangulation). Interviews revealed that Bachelor students should be educated to
      retrieve and criticise scientific literature, to apply research finding in
      practice and to collaborate in research studies; Master students should improve
      knowledge of Bachelor degree and be able to design and conduct research studies.
      Participants emphasised the importance of using active methodologies for teaching
      and to involve students in research. By analysing the literature and the results
      of the present study educational objectives for teaching nursing research at
      Bachelor and Master degree are defined.

PMID- 16945225
TI  - [Efficacy and compliance of hip protectors in preventing fractures in the
      elderly: review of literature].
AB  - Hip fracture resulting from a fall is one of the main causes of morbidity and
      functional decay in elderly people. Hip protectors, plastic shields or foam pads
      fitted in pockets within specially designed underwear could represent an
      interesting preventive measure available to nursing staff caring for elderly
      people. The literature from 1993 to July 2005 was reviewed to assess the efficacy
      and compliance of such devices. In fact, the efficacy of this measure is still
      controversial because although there is some evidence that in institutions with
      high rates of hip fracture the use of hip protectors may help to reduce this
      incidence, there is no evidence of this being true for the majority of older
      people living at home. Compliance remains poor due to discomfort the practical
      impairment related to continuous wear of the device. While awaiting further
      evidence, nursing staff should not use the protectors as a routine measure to
      prevent hip fracture in institutionalized elderly people and outside a research
      program. Instead, they should concentrate on the implementation of those
      preventive measures that have been proved effective.

PMID- 16945226
TI  - [Reflections on the meaning of nursing work loads and responsibility to establish
      safe staffing].
AB  - The methods for establishing nursing staff requirements , based on the caring
      needs of patients , take into consideration two parameters: the determination of
      the overall care requirements fundamental for programming nursing care; the
      quantification of the requirements as the time needed for care, classifying
      patients according to their degree of dependence, by the analysis of the pre
      established parameters. Consequently, the approach to the evaluation of nursing
      staff requirements varies: in fact, when the focus is placed on the care
      necessary for different types of patients, the nursing practice is based on
      planning of care and the resulting criteria are more objective. On the other
      hand, when the approach focuses on an analysis of the division of available
      resources among the different types of patients, it is influenced by local
      factors and is less objective. The DRG system introduced in Italy in 1995
      classifies patients on a medical basis and allocates resources accordingly.
      However, since this system does not take into account a nursing classification,
      it cannot extrapolate the true requirements of nursing resources: this means that
      financing does not adequately evaluate the costs of nursing care. The non
      assessable aspects of nursing care and their significance are also taken into
      consideration.

PMID- 16945227
TI  - PBL-the perspective.

PMID- 16945228
TI  - Plaque formation reduction with glutathione monoester in mice fed on atherogenic
      diet.
AB  - OBJECTIVE: To determine the role of glutathione monoester on reducing the
      development of plaque formation in an animal model. DESIGN: Laboratory control
      trial. PLACE AND DURATION OF STUDY: Aga Khan University, Karachi, from January
      2004 to December, 2004. MATERIALS AND METHODS: Twenty-four Balb/c mice were
      divided into 3 equal groups. First group was fed on atherogenic diet alone, while
      the second group received atherogenic diet plus twice weekly injections of
      glutathione monoester. The third group was fed on normal diet for mice. After one
      year, the animals were sacrificed. Blood was analyzed for lipid levels, while
      liver, kidney, spleen, heart and aorta were removed to study morphological
      changes. RESULTS: In the groups of mice receiving atherogenic diet (with and
      without glutathione monoesters), there was significant increase in levels of
      total cholesterol (p=0.011) and LDL cholesterol (p=0.001) compared to levels of
      these lipids in mice on normal diet. However, a significant decrease in levels of
      triglycerides (p=0.01) was observed in the group receiving atherogenic diet along
      with glutathione monoester. Supplementation with glutathione monoester had the
      most pronounced effect only on triglyceride levels. Atherosclerotic plaques were
      seen in heart and/or aorta of mice receiving atherogenic diet. However, such
      plaques were either totally absent or if seen in an animal, were extremely small
      and diffuse in the group receiving glutathione monoester along with atherogenic
      diet. Mice on normal diet had no evidence of any plaque formation. Cholesterol
      granuloma was seen in liver of mice on atherogenic diet alone. In mice receiving
      atherogenic diet plus glutathione monoester, no cholesterol granuloma was found
      in liver. There were no remarkable morphological changes in spleen and kidney in
      the three groups of mice. CONCLUSION: Glutathione monoester appears to inhibit or
      reduce the development of plaque formation in mice.

PMID- 16945229
TI  - Correlation of serum cortisol levels and stress among medical doctors working in
      emergency departments.
AB  - OBJECTIVE: To assess and correlate serum cortisol levels and self-perceived work
      related stress among medical doctors working in emergency departments in
      different tertiary care hospitals of Karachi. DESIGN: Cohort study. PLACE AND
      DURATION OF STUDY: The study was conducted in Section of Chemical Pathology,
      Department of Pathology and Microbiology, AKUH, from December 2004 to August
      2005. SUBJECTS AND METHODS: A total of 64 doctors participated from one private
      and two public tertiary care hospitals of Karachi. Thirty-four doctors were from
      emergency departments and 30 from non-emergency departments. Serum cortisol
      levels were measured in the morning (between 8.00-8.30 am) and in the evening
      (between 8.00-8.30 pm). Cortisol was measured by Florescence Polarization
      Immunoassay (FPIA) technique. Two questionnaires, modified mental Professional
      Stress Scale (PSS) and Aga Khan University Anxiety and Depression Scale (AKUADS)
      were used to assess stress levels. RESULTS: Emergency room physicians (ERP) were
      1.2-year younger than non-emergency room physicians (NERP). Mean evening cortisol
      of emergency physicians was 60.72nmol/L higher than non-emergency physicians. The
      difference between morning and evening cortisol was marginally significant (p =
      0.051). Morning diastolic blood pressure was 3mmHg higher in emergency
      physicians. Forty-one percent of emergency physicians and 20% of non-emergency
      physicians had AKUADS more than or equal to 20, the difference was borderline
      significant (p = 0.068). Mean value of professional stress scale for emergency
      physicians was significantly higher than non-emergency physicians. Evening serum
      cortisol concentration was significantly associated with PSS (p = 0.011). The sub
      scales such as work-load (p = 0.007) and lack of resources were highly
      significant with evening cortisol (p = 0.005). CONCLUSION: In this study, evening
      serum cortisol levels significantly correlated with work overload and lack of
      resources, however, there was marginally significant correlation between morning
      and evening serum cortisol difference. Study suggests that emergency physicians
      perceive more stress than non-emergency physicians. Work overload and lack of
      resources are major contributing factors for stress in these doctors.

PMID- 16945230
TI  - Frequency and comparative analysis of hapatitis D in petients seeking treatment
      for hepatitis B.
AB  - OBJECTIVE: To find the frequency of hepatitis 'D' in patients of hepatitis 'B'
      seeking treatment and to compare clinical and biochemical features in patients
      harboring HDV with those who are not. DESIGN: Cross-sectional study. PLACE AND
      DURATION OF STUDY: Medical Unit-IV, Civil Hospital Karachi, Medical Unit-VI and
      Surgical Unit-VII, Lyari General Hospital, Dow University of Health Sciences,
      Karachi; from July 2003 to June 2005. PATIENTS AND METHODS: HBsAg positive
      patients seeking treatment were enrolled in the study. Anti-HDV was done in all.
      Patients were split into two groups according to their anti-HDV status into HDV
      positive and HDV negative groups. Liver biochemistries and viral profile for HCV,
      anti-HBc IgM and HBeAg were done and compared between the two groups. RESULTS: A
      total of 246 patients were selected. HDV was positive in 66 (26.8%) patients. No
      significant difference was observed in the frequency and stages of cirrhosis
      between the two groups while significant differences were observed in the mean
      SGPT (95% CI: -381.09 to -110.74; P = 0.001) and albumin levels (95% CI: 1.87 to
      7.73; P = 0.007) and in the frequency of HBeAg (P = 0.001), anti-HBc IgM (P =
      0.02) and HBV DNA (P<0.001). CONCLUSION: HDV infection was common in patients
      with HBV in this cohort of patients. All patients of HBV should be screened for
      HDV before treatment decision for the former is taken.

PMID- 16945231
TI  - Cardiorespiratory compromise under conscious sedation during upper
      gastrointestinal endoscopy.
AB  - OBJECTIVE: To compare the cardiorespiratory effects of benzodiazepine and
      midazolam used for sedation in patients undergoing upper gastrointestinal
      endoscopy with cardiorespiratory changes in the non-sedated patients. STUDY
      DESIGN: Comparative, randomized, single blind study. Duration and Setting:
      Department of Medicine at Government Medical College and Hospital, Chandigarh,
      India, from January to July 2000. PATIENTS AND METHODS: A total of 252 adult
      patients without previous cardiorespiratory co-morbidity, undergoing upper
      gastrointestinal endoscopy were recruited. They were randomly allocated in to
      group I (placebo with saline administration), group II (diazepam administered)
      and group III (midazolam administered). The pulse rate, blood pressure, ECG and
      peripheral oxygen saturation (SpO2) was noted at baseline, after pre-medication,
      during endoscopy and postendoscopy. Statistical analysis was done by paired t
      test, Chi-square test and ANOVA as applicable. RESULTS: There was no difference
      in baseline record of the three groups. Significant fall in SpO2 was noted in all
      the groups, more marked in the sedated one during endoscopy. Tachycardia
      developed in all the three groups and settled within 5 minutes of endoscopy.
      Blood pressure remained more stable in the sedated group. ECG changes included
      atrial and ventricular premature contraction in all the three groups. CONCLUSION:
      Endoscopy is a safe procedure where cardiorespiratory complication are minimized
      in non-sedated patients when appropriately selected.

PMID- 16945232
TI  - Usefulness of crush smears intraoperative consultaion of neurological biopsis.
AB  - OBJECTIVE: To evaluate accuracy of intraoperative crush smears diagnosis of
      neurosurgical biopsies. DESIGN: Cross-sectional study. PLACE AND DURATION OF
      STUDY: The Armed Forces Institute of Pathology, Rawalpindi, from February 2002 to
      February 2003. PATIENTS AND METHODS: One hundred, neurosurgical biopsies were
      received for intraoperative consultation over a period of one year. Clinical
      information regarding age, gender, history, and CT scan or MRI findings were
      recorded. Crush smears were prepared, fixed in 95% alcohol and stained with rapid
      haemotoxylin and eosin (H&E) stains. Diagnosis was categorized into inflammatory,
      benign and malignant tumours. Remaining tissue was fixed overnight in 10%
      formalin for histological sections. Permanent H&E sections were used as the gold
      standard. The average time required for intraoperative cytological diagnosis was
      8 minutes. RESULTS: Out of 100 neurosurgical biopsies, crush smears of 94 were
      considered suitable for interpretation. There were 8 inflammatory, 41 benign and
      41 malignant tumours, including 4 inconclusive. Eightyfour of the crush smears
      diagnosis agreed with the histological diagnosis. Overall diagnostic accuracy of
      crush smears was 93.3%. Diagnosis of inflammatory, benign and malignant tumours
      showed specificity of 98.7%, 96% and 94%, and a sensitivity of 70%, 97.5% and 95%
      respectively. CONCLUSIONS: Crush smears are useful in the intraoperative
      diagnosis of space occupying lesions of central nervous system. The crush smears
      cytology was found highly reliable, rapid and inexpensive mode of intraoperative
      diagnosis.

PMID- 16945233
TI  - Correlation of the size of undescended testis with its locations in vatrious age
      groups.
AB  - OBJECTIVE: To assess the correlation of the size of undescended testis with its
      location in children of various age groups, per-operatively. DESIGN: Cross
      sectional study. PLACE AND DURATION OF STUDY: Surgical Unit B, National Institute
      of Child Health, Karachi from February 2004 - November 2005. PATIENTS AND
      METHODS: Children presenting with undescended testis at surgical outpatient were
      recruited. Physical examination and relevant investigations (haemoglobin,
      ultrasound for location and size of testes) were performed. Patients were divided
      randomly into three age groups, group I (8 months - 2.5 years), group II (2.6 - 8
      years), group III (8.1-13 years). At orchiopexy location and size of undescended
      testis were noted. Patients were further sub-divided into groups according to
      peroperative location of undescended testis, group A (intra-abdominal), group B
      (intra-canalicular), group C (distal to superficial inguinal ring - pubic). Where
      no testis was found, a separate group D was assigned. The size of undescended
      testis at different locations in various age groups was compared with reference
      to normal descended testicular size in the respective age group, for statistical
      significance. ANOVA test was used for intergroup comparison for the size of
      undescended testis and Student t- test was applied for comparison with reference
      to normal values of the size of testis. RESULTS: A total of 102 patients with
      undescended testis were included in the study. The total number of 107 testicular
      units were assessed. Group I had 28, group II, 41 and group III, 38 testes. There
      were 24 intra-abdominal, 68 intra-canalicular and 12 pubic in location. In 3
      cases, no testis was found at exploration. We found no statistically significant
      difference amongst groups (p-value=0.090) between the size of the undescended
      testis at different peroperative locations. The size of undescended testis grew
      with the age as undescended testis of larger size were found in older age group
      as compared to younger age group. By applying Student t-test, we did not find
      statistically significant difference in relation to the size of undescended
      testis in various age groups in comparison to the reference of mean volume of
      normally descended testis in the respective age groups. CONCLUSION: Pre-pubertal
      size of undescended testis does not differ significantly from that of normal
      reference value of descended testis in relation to age and location. The ultimate
      size of the testis can only be assessed after puberty whether it is a normally
      descended or undescended testis.

PMID- 16945234
TI  - Successful pulmonary venous channeling in a case of scimitar syndrome.
AB  - A young girl child with recurrent pneumonias, failure to thrive and dextroposed
      heart was diagnosed with and surgically treated for scimitar syndrome. Early
      diagnosis and treatment of this syndrome prevents serious morbidity.

PMID- 16945235
TI  - Primary intrathoracic goiter -a rare mediastinal tumor.
AB  - Primary intrathoracic goiter is a rare presentation of thyroid disease. Its
      removal usually necessitates thoracotomy or sternotomy. This patient having a
      primary intrathoracic goiter presented with posterior mediastinal mass that was
      removed through a right lateral thoracotomy.

PMID- 16945236
TI  - Meigs' syndrome.
AB  - Meigs' syndrome is a rare clinical condition commonly considered to be associated
      with malignant ovarian tumour. A case of unmarried female is presented who came
      with a slowly increasing abdominal mass. Clinical and ultrasonic investigations
      revealed a mobile, solid right adenexal tumour in the lower abdomen, along with
      ascites and pleural effusion of the right lung. The level of CA 125 was also
      raised. Diagnosis of Meigs' syndrome was confirmed after surgical intervention.
      The tumour was successfully removed and pleural effusion disappeared 15 days
      after the intervention. Cytomorphologic study of both the tumour and ascitic
      fluid was negative for malignancy.

PMID- 16945237
TI  - Myotonia congenita in a brother and sister.
AB  - Myotonia congenita is a rare channelopathy and carries a good prognosis. Two
      cases of young siblings are presented detected with difficulty in gait and motor
      activities. Both had typical hypertrophied body musculature. EMG was diagnostic.

PMID- 16945239
TI  - Problem based learning in medical education: theory, rationale, process and
      implications for pakistan.
AB  - Historically, lectures were the medium to transfer cognitive information to the
      learners in medical education. Apprenticeship training, labs, bedside teaching,
      tutorials etc. were used to impart psychomotor and affective skills. It was
      assumed that the learner will assimilate all this knowledge and will be competent
      to apply this learning in practical life. Problem-based learning (PBL) emerged
      due to problems in building the appropriate competencies in the medical graduates
      and is a relatively newer mode of transfer of knowledge. This paper will deal
      with problem-based learning which took the world with storm in the 80's and most
      institutions in the world started using different variants of PBL. This paper
      attempts to define and explore the theoretical basis and historical background of
      PBL. The paper will systematically review literature and argue about the
      advantages and disadvantages of PBL and the implications of its implementation in
      Pakistan.

PMID- 16945238
TI  - Medullary carcinoma of breast with a novel germline mutation 1123T >G in exon 11
      of BRCA1.
AB  - Breast cancer, the most common malignancy in females, has an estimated 5-10%
      hereditary predisposition. BRCA1 is a tumor suppressor gene and is known to be
      responsible for breast cancer and breast-ovarian cancers running in families. In
      breast caner patients, several mutations in BRCA1 have been reported throughout
      the gene. This report describes identification of a mutation in BRCA1 gene using
      protein truncation (PTT) assay in a patient with medullary carcinoma of breast
      who also had a family history of breast cancer. Following DNA sequencing, the
      mutation was confirmed as substitution of thymine at position 1123 with guanine
      of exon 11 (1123 T>G). This mutation can be added to the pool of known BRCA1
      mutations in Pakistani population, which will help in developing a local
      screening panel of BRCA1 mutations.

PMID- 16945240
TI  - Desmoplastic small round cell tumor.
AB  - Desmoplastic small round cell tumour (DSRCT) is a unique, highly aggressive
      neoplasm that chiefly affects adolescent male and young adults and most
      frequently presents as a large abdominal mass with widespread peritoneal
      involvement at the time of diagnosis. Histologically, it is composed of nests of
      small, undifferentiated round or oval hyperchromatic cells embedded in abundant
      desmoplastic stroma. Co-expression of epithelial, mesenchymal, and neural
      antigens in the same cell provides evidence of origin from a primitive
      pluripotent stem cell with multiphenotypic differentiation. A multidisciplinary
      treatment including high-dose chemotherapy, aggressive debulking surgery,
      radiation and myeloablative chemotherapy with stem cell rescue might be the
      proper approach to treat this rare malignancy and may improve progression-free
      survival.

PMID- 16945241
TI  - Current radiologic interventions in hepatocellular carcinoma.
AB  - With the rising incidence of chronic liver disease caused by viral hepatitis,
      hepatocellular carcinoma is showing a corresponding rise worldwide. Surgery
      remains the mainstay of treatment, but patients unfit for surgery or liver
      transplantation form the bulk of those presenting with this disease. Palliative
      treatments are being used to treat those and radiological modalities form the
      mainstay of the treatment. Radiology plays a major role in the diagnosis,
      treatment and follow-up of hepatocellular carcinoma. Current radiological
      treatment modalities include percutaneous ethanol ablation, radiofrequency
      ablation and trans-arterial chemoembolization. This update highlights the recent
      advancements in the field and compares their relative merits and demerits.

PMID- 16945242
TI  - The cost of unsafe injections in pakistan and challenges for prevention program.
AB  - The burden of disease associated with unsafe therapeutic injection practices in
      Pakistan is very high. The number of injection per person per year has been
      estimated to be in the range of 8.2 to 13.6, one of the highest in developing
      world. Extrapolating this number to the whole country would result in 1.5 billion
      injections per year. Approximately 4% (75 million) of these are administered for
      immunization while the remainders are used for therapeutic use. Of these, 94.2%
      are unnecessary. Average price of an injection (not the complete prescription) is
      Rs. 20.6 (0.34 US dollars). Under conservative estimate, over three billion
      rupees or 500 million dollars out-of-pocket healthcare resources may be wasted
      each year. Appropriate use of injections would be highly cost effective.
      According to adjusted analysis, safe and appropriate use of injection in Pakistan
      would cost 92 million US dollars each year with a high proportion that would be
      injection devices paid through out-of-pocket expenses. Behaviour change for
      reduction in number of injections require long-term multidimentional efforts.
      Interventions in the form of phasing out of convention disposable injection
      equipment and switching to reuse prevention devices for all injections could
      prevent the common practice of reuse, hence reducing the transmission of
      infections.

PMID- 16945243
TI  - Spectrum and outcomes of infections in systemic lupus erythematosus pateients.

PMID- 16945244
TI  - Dental education in pakistan: perception and perspectives.

PMID- 16945245
TI  - Segmental neurofibromatosis.

PMID- 16945246
TI  - Massive splenomegaly with pancytopenia in children and adolescents with hepatitis
      B cirrhosis.

PMID- 16945247
TI  - Update on rheumatologic mimics of fibromyalgia.
AB  - Fibromyalgia is a common disorder of diffuse musculoskeletal pain. Several
      rheumatic diseases can mimic fibromyalgia, and a clinician would not want to miss
      these diagnoses because of their potential long-term sequelae, such as
      progressive joint damage or life- or organ-threatening disease if they remain
      untreated. This paper discusses the typical clinical presentations of selected
      rheumatic diseases (systemic lupus erythematosus, rheumatoid arthritis,
      ankylosing spondylitis, polymyalgia rheumatica, and osteoarthritis) then
      highlights the key features in history, laboratory testing, and radiographic
      imaging that aid the clinician in differentiating between fibromyalgia and these
      rheumatic diseases.

PMID- 16945248
TI  - Physical therapy and other nonpharmacologic approaches to fibromyalgia
      management.
AB  - Fibromyalgia is a vague and changing syndrome that comprises many symptoms. Due
      to the confounding nature of fibromyalgia syndrome, there has been much debate
      about which interventions and therapies should be considered as viable treatment
      options. Opinions continue to shift in publication and research circles, with
      little documentation to show good, long-term outcomes. Several studies have shown
      promise, with initial improvement in symptoms, but in many cases, these
      improvements were not lasting or the patients were then unable to
      continue/replicate the program on their own. In this article, some of the more
      recently published findings regarding the efficacy of exercise are explored,
      specifically physical therapy and other nonpharmacologic interventions, for
      managing fibromyalgia syndrome.

PMID- 16945249
TI  - Soft tissue determinants of low back pain.
AB  - Low back pain is one of the complaints most commonly seen in the clinical
      setting. Correctly or incorrectly, these patients are often given the diagnosis
      of fibromyalgia, myofascial pain syndrome, disk herniation, or some other label.
      It is important to recognize the soft tissue causes of low back pain and
      understand how they can be most appropriately diagnosed and managed.
      Nonligamentous disorders of the low back region may occur in isolation or in
      combination with underlying discogenic, ligamentous, and facet-mediated causes of
      pain. Therefore, in order to fully evaluate and treat a patient with low back
      pain, it is necessary to consider and address these soft tissue conditions. This
      paper reviews soft tissue causes of low back pain and discusses how they are most
      appropriately diagnosed and managed.

PMID- 16945250
TI  - Treatment of myofascial pain syndrome.
AB  - Myofascial pain syndrome (MPS) is caused by myofascial trigger points (MTrPs)
      located within taut bands of skeletal muscle fibers. Treating the underlying
      etiologic lesion responsible for MTrP activation is the most important strategy
      in MPS therapy. If the underlying pathology is not given the appropriate
      treatment, the MTrP cannot be completely and permanently inactivated. Treatment
      of active MTrPs may be necessary in situations in which active MTrPs persist even
      after the underlying etiologic lesion has been treated appropriately. When
      treating the active MTrPs or their underlying pathology, conservative treatment
      should be given before aggressive therapy. Effective MTrP therapies include
      manual therapies, physical therapy modalities, dry needling, or MTrP injection.
      It is also important to eliminate any perpetuating factors and provide adequate
      education and home programs to patients so that recurrent or chronic pain can be
      avoided.

PMID- 16945251
TI  - The physical examination of migraine.
AB  - Patients and physicians are frequently unaware that pain coming from the muscles
      of the head and neck is probably the cause of the most frequent forms of
      migraine. Identifying the extracranial origins of the patient's headache by
      physical examination should reassure patient and examiner that the headache is
      benign and treatable. The results of the examination should lead to physical
      treatment, reducing headache frequency and severity. This paper describes
      techniques of the physical examination to identify the extracranial causes of
      migraine headache.

PMID- 16945252
TI  - The role of botulinum toxin in whiplash injuries.
AB  - Cervical whiplash injuries are common and yet poorly understood. Several of these
      cases become chronic for unknown reasons and defy most forms of musculoskeletal
      therapy. Botulinum toxin has shown promise in selected cases in which soft tissue
      injury predominates. In conjunction with a good biomechanical assessment and
      appropriate physical rehabilitation techniques, this new approach to treatment
      may offer a way of treating the central and peripheral dysfunction that
      characterizes this condition.

PMID- 16945253
TI  - Diagnosing migraine in the pediatric population.
AB  - Migraine in the pediatric population remains substantially underdiagnosed and
      undertreated. The recently revised International Classification of Headache
      Disorders is a step in the right direction to improve our diagnostic accuracy.
      This article reviews the practical diagnostic issues related to migraine in the
      pediatric population.

PMID- 16945254
TI  - Chronic daily headaches in children.
AB  - Chronic daily headache (CDH) is increasingly recognized as a problem in
      pediatrics and tertiary pediatric headache care. It is estimated that up to 4% of
      the adult population has CDH. Many of these are chronic migraine (CM). The
      fraction of the pediatric population with CDH appears to be lower, although the
      prevalence has not been adequately determined. The simplest definition of CDH is
      more than 15 headache days per month. In the International Classification of
      Headache Disorders, Second Edition (ICHD-II), several types of CDH have been
      identified. These criteria have been contrasted with the Silberstein-Lipton
      criteria, with revisions suggested. The diagnosis of CDH is further complicated
      and may be initiated by the overuse of analgesic medications (medication overuse
      headache) and requires the resolution of this issue before a final diagnosis can
      be established. In children, most CDH appears to have migraine features, although
      it may not completely meet the ICHD-II criteria for migraine or CM. Evaluation of
      CDH needs to include a complete history and physical examination to identify any
      possibility of the secondary headaches or headaches directly attributed to a
      secondary cause. Treatment and management involve a multidisciplinary approach,
      including acute therapy for when the headache severity increases (while avoiding
      medication overuse), preventative therapy to reduce the frequency and impact of
      the CDH, and biobehavioral therapy to assist with long-term outcome.

PMID- 16945255
TI  - Pharmacologic treatment of migraine.
AB  - Nonsteroidal anti-inflammatory drugs are the mainstay of migraine treatment for
      children and adolescents by most primary care physicians. Not all patients
      respond to these readily available agents. Triptans have been studied in children
      and adolescents, and there is reasonable evidence to support the use of these
      agents in these populations. Other agents, such as combination preparations and
      ergot compounds, are also used in clinical practice, although there has been
      little scientific study. Prophylactic agents have been less well studied in those
      under 18 years of age. Agents such as antidepressants, anticonvulsants, and
      antihypertensives are commonly used in clinical practice. Safety issues are
      fairly well understood because of historical use and use for other conditions.
      Efficacy and optimal dosing have yet to be established for the treatment of
      migraine in children and adolescents in double-blind, randomized, placebo
      controlled trials.

PMID- 16945256
TI  - Secondary headaches.
AB  - In this article, we develop an approach to the headache patient based upon
      pattern of headache. Headache can be acute recurrent, acute, chronic progressive,
      and chronic nonprogressive. Within each pattern we go through the differential
      diagnosis, with a focus on secondary causes of headache. Although most patients
      presenting with headache will end up having migraine, we must be able to
      recognize the other causes when they present.

PMID- 16945257
TI  - Pediatric post-traumatic headache.
AB  - Post-traumatic headache after craniocerebral trauma is not an uncommon occurrence
      in children and adolescents. It can occur after mild, moderate, or severe injury.
      The headache may have features of tension-type headache, migraine, or probable
      migraine and is rarely seen in isolation. It is often part of a syndrome
      encompassing a variety of somatic and psychobehavioral symptoms. In time, the
      headache and accompanying symptoms gradually resolve over a period of 8 to 12
      weeks. However, sometimes it may become chronic, requiring a multidimensional
      management approach including pharmacologic intervention, physical
      rehabilitation, and cognitive-behavioral therapy as used in the adult population.

PMID- 16945258
TI  - Pediatric headaches in the emergency department.
AB  - Headache is a common presenting complaint in the pediatric emergency department.
      Although the majority of headaches are benign in nature, headache may be
      secondary to more serious pathology, such as tumor, meningitis, hemorrhage, or
      brain abscess. A systematic history will elicit the temporal pattern of the
      headache, guiding the development of an appropriate differential diagnosis.
      Thorough physical and neurologic examinations will disclose the objective signs
      that dictate the need for further diagnostic testing.

PMID- 16945259
TI  - [Are quality and the extensive use of spirometry compatible?].

PMID- 16945260
TI  - [Diagnostic imaging techniques for pulmonary embolism].

PMID- 16945261
TI  - [Spirometric reference values in 5 large Latin American cities for subjects aged
      40 years or over].
AB  - OBJECTIVE: In clinical practice, spirometry is a extremely useful test that
      requires strict quality control, an appropriate strategy for interpretation, and
      reliable reference values. The aim of this study was to report spirometric
      reference values for 5 cities in Latin America. PATIENTS AND METHODS: From data
      for 5315 subjects who had undergone spirometry in the PLATINO study in Caracas,
      Mexico City, Santiago, Sao Paulo, and Montevideo, we selected information for 906
      (17%) individuals aged between 40 years and 90 years to provide reference values.
      The chosen subjects had never smoked, were asymptomatic, had not been diagnosed
      with lung disease, and were not obese. Multiple regression models were
      constructed with the following spirometric parameters: forced expiratory volume
      in 1 second (FEV1) and in 6 seconds (FEV6), peak expiratory flow, forced vital
      capacity (FVC), FEV1/FEV6, FEV1/FVC, and forced midexpiratory flow rate. Height,
      sex, and age were also included in the model. RESULTS: Average values for the
      subjects studied were similar to those for the white North American population
      and the Mexican-American population of the third National Health and Nutrition
      Examination Survey, but exceeded those of the black population of the same survey
      by 20%. CONCLUSIONS: The proposed reference values are an improvement on those
      currently available for Latin America because the participants were chosen by
      population sampling methods and standardized up-to-date methodology was used.

PMID- 16945262
TI  - [Spirometry in primary care in Navarre, Spain].
AB  - OBJECTIVE: To analyze the use and quality of spirometry in primary care settings
      in Navarre, Spain. PATIENTS AND METHODS: A questionnaire was completed
      simultaneously by professionals responsible for spirometry in all of the primary
      health care centers in Navarre. Data were collected on availability, model of
      spirometer, frequency of use, calibration, methods, personnel responsible for
      testing, and training of personnel. Then, baseline spirometry without a
      bronchodilator test was performed in 171 patients in their primary health care
      center and then the test was repeated on the same day in a hospital pneumology
      department. Spirometry was supervised by 2 pneumologists who jointly assessed the
      acceptability of the flow-volume curves. The quality of spirometry was assessed
      according to the recommendations of the American Thoracic Society and the
      interpretation of spirometry results according to the criteria of the Spanish
      Society of Pulmonology and Thoracic Surgery (SEPAR). RESULTS: A total of 90.9% of
      primary health care centers in Navarre have a spirometer, although 22% of those
      spirometers have never been used. Only 2 centers performed between 10 and 20
      spirometry tests per week and none performed more than 20. In 96% of primary
      health care centers the spirometers were not regularly calibrated. The
      professionals who performed spirometry were not dedicated for that task in 51.2%
      of cases, and the mean period of supervised training was 10 hours. When
      comparisons were made between the mean values obtained in the primary care
      centers and the pneumology department, statistically significant differences were
      detected for forced vital capacity (P < .0001) and forced expiratory volume in
      the first second (P = .0002). Significant differences were also found between the
      flow-volume curves performed in the 2 different care settings for the initial and
      end portions of the curve as well as for the slope. The criteria for
      reproducibility recommended by the American Thoracic Society were not met in 76%
      of cases for forced vital capacity and 39.7% of cases for forced expiratory
      volume in the first second. Incorrect functional diagnosis occurred in 39.7% of
      spirometry tests and there was a tendency in the primary care settings to falsely
      diagnose patterns as restrictive and to inadequately classify the severity of
      obstruction. CONCLUSIONS: Despite the fact that spirometers are available in the
      majority of primary health care centers in Navarre, we found a marked underuse of
      these devices and little compliance with recommendations for the use of
      spirometry. Furthermore, the quality of the measurements performed in this care
      setting was very low.

PMID- 16945263
TI  - [Systemic and lung inflammation in 2 phenotypes of chronic obstructive pulmonary
      disease].
AB  - OBJECTIVE: To study whether patients with chronic obstructive pulmonary disease
      (COPD) at the same level of flow limitation but with different clinical
      phenotypes present different degrees of systemic and/or pulmonary inflammation.
      PATIENTS AND METHODS: We studied 15 male smokers without COPD (control group) and
      39 males with COPD in stable clinical condition. The COPD patients were assigned
      to 2 groups based on the ratio of carbon monoxide diffusing capacity (DLCO) to
      alveolar volume (DLCO/VA) expressed as a percentage as follows: a) mainly
      emphysema (n = 15) and b) mainly chronic bronchitis (n = 24). Classification was
      determined by comparing both clinical features and diagnostic images. RESULTS:
      Mean (SD) concentrations of interleukin 8 (IL-8) and 8-isoprostane in exhaled
      breath condensate (EBC) were significantly lower in patients with mainly
      emphysema (IL-8, 0.34 [0.70] pg/mL; 8-isoprostane, 0.07 [0.26] pg/mL) than in
      patients with chronic bronchitis (IL-8, 2.32 [3.10] pg/mL; 8-isoprostane, 1.77
      [2.98] pg/mL) or in the controls (IL-8, 3.14 [4.59] pg/mL; 8-isoprostane, 1.92
      [2.84] pg/mL); P < .05 for IL-8 comparisons and P < .01 for 8-isoprostane. IL-8,
      leukotriene B4, and 8-isoprostano in EBC correlated significantly with DLCO/VA (%
      of predicted) (r = 0.30, P < .05; r = 0.29, P < or = .05; and r = 0.46, P < .01,
      respectively) but not with forced expiratory volume in 1 second. There was a
      negative correlation between EBC and serum levels of both IL-8 (r = -0.31; P <
      .05) and 8-isoprostane (r = -0.51; P < .001). The correlation between leukotriene
      B4 concentrations in EBC and serum was not significant, however. No significant
      differences were found between smokers' and ex-smokers' serum levels of IL-8,
      leukotriene B4, 8-isoprostane in serum or EBC. CONCLUSIONS: The results indicate
      that COPD patients with an emphysematous phenotype have a less intense
      inflammatory response and less oxidative stress in the lung.

PMID- 16945264
TI  - [Optimizing exercise performance with a continuously paced shuttle walk test for
      patients with chronic obstructive pulmonary disease].
AB  - BACKGROUND: A continuously paced shuttle walk test (SWTp) was developed to test
      the hypothesis that speed and rhythm could be more optimally imposed by an easier
      to-follow sound stimulus at every step. The objective of this study was to assess
      the reproducibility of the SWTp and to compare the performance of patients with
      chronic obstructive pulmonary disease (COPD) on the conventional and optimally
      paced forms of the test. PATIENTS AND METHODS: The walk test results of 24 COPD
      patients were studied. All patients completed 2 SWTp sessions and a conventional
      SWT in random order, after an initial practice test for each. A portable device
      was used to measure peak oxygen uptake (VO2) in 6 patients. RESULTS: The
      intraclass correlation coefficient (Cronbach's alpha) was 0.95 for the STWp. The
      Pearson correlation coefficient between distance walked and peak VO2 in the SWTp
      was 0.86 (P < .02). Better performance was achieved during the SWTp (peak VO2,
      3.30 mL/kg/min; P < .01; distance walked, 32 m, P < .001) than during the
      conventional SWT. The SWTp showed excellent reproducibility. CONCLUSIONS: COPD
      patients can achieve better performance with the stimuli provided in the SWTp
      than on the SWT.

PMID- 16945265
TI  - [Thromboembolic events in patients after a negative computed tomography pulmonary
      angiogram: A retrospective study of 165 patients].
AB  - OBJECTIVE: To determine the value of computed tomography (CT) angiography of the
      chest as a diagnostic test to exclude pulmonary embolism and to assess compliance
      with diagnostic protocols for thromboembolic disease. PATIENTS AND METHODS: We
      retrospectively studied patients who underwent CT angiography of the chest
      because of suspected pulmonary embolism in 2004. All the patients were followed
      for 3 months. The percentage of patients diagnosed with a thromboembolic event
      based on an objective test during the follow-up period was determined. We
      analyzed the percentage of patients with a negative CT angiogram on whom
      additional diagnostic tests (ultrasound of the lower limbs and/or ventilation
      perfusion lung scintigraphy) were performed. RESULTS: One hundred sixty-five
      patients underwent CT angiography of the chest because of suspected pulmonary
      embolism in 2004. Four of the patients were excluded from the study because they
      were on chronic anticoagulation therapy and a further 2 were excluded because
      they had a life expectancy of under 3 months. Of the remaining 159 patients, 60
      had CT angiograms that were interpreted as high probability for pulmonary
      embolism (prevalence of 38%). Thirty-nine of the 99 patients with a negative CT
      angiogram experienced an objectively confirmed thromboembolic event (63%
      sensitivity; 95% confidence interval, 53%-73%). Other diagnostic tests were not
      performed in 46% of the cases. CONCLUSIONS: In our setting, a negative single
      detector helical CT angiogram was not sensitive enough to exclude the diagnosis
      of pulmonary embolism. Furthermore, compliance with internationally accepted
      diagnostic protocols was far from optimal.

PMID- 16945266
TI  - [Diagnosis and treatment of pleural effusion].

PMID- 16945267
TI  - [Economy-class syndrome or Immobile Traveler's syndrome?].
AB  - Economy class syndrome describes the situation of patients who suffer pulmonary
      embolism following prolonged immobility in a long distance flight. The objective
      of the present study was to analyze whether there is a risk of pulmonary
      thromboembolism after a long overland journey. The study consecutively enrolled
      100 patients diagnosed with pulmonary thromboembolism. Nine of them had
      previously undertaken a long journey (>5 h), 6 of which had been over land.
      Consequently, we think that the preventative measures recommended for airline
      passengers should be extended to users of other means of transport.

PMID- 16945268
TI  - [Etymologies].

PMID- 16945269
TI  - [Addisonian crises induced by rifampicin].

PMID- 16945270
TI  - [Consensus document about the use of antibiotics in primary care].

PMID- 16945271
TI  - [Peripheral artery disease of the lower limbs and morbidity/mortality in type 2
      diabetics].
AB  - OBJECTIVE: To study the relationship between the presence of peripheral artery
      disease (PAD) and the morbidity and mortality at 6 years, and the ankle-brachial
      index (ABI) as a predictor of morbidity and mortality in type 2 diabetes
      mellitus. DESIGN: Retrospective cohort study. Six years follow-up. SETTING: Urban
      health centre. PARTICIPANTS: A total of 269 type 2 diabetics, of which 63 had PAD
      in 1996: 20 were previously diagnosed and 43 had an ABI of < or =0.90. PRINCIPAL
      MEASUREMENTS: An appointed was made with the patients to find out the incidence
      of fatal and non-fatal microvascular and macrovascular events and the histories
      were reviewed. Six patients were excluded as all their data were not available.
      RESULTS: Thirty nine patients had died, of whom 19 had PAD in 1996 (30.1%) and 20
      did not (9.7%) (P = .001). Sixteen patients died in the group with an ABI < or
      =0.9 (30.2%) and 21 (10.1%) in the group with normal ABI values (P = .001). 7
      (13.2%) patients died due to a cardiovascular cause with a pathological ABI, and
      8 (3.9%) with a normal value (P = .009). The presence of PAD has been associated
      with a higher probability of having a non-fatal episode of ischaemic cardiac
      disease (P = .04), a cerebrovascular accident (CVA) (P < .001) and ulcers (P =
      .006). A low ABI has been associated with a higher probability of presenting with
      a fatal or non-fatal cardiovascular event (P < .001). After the multivariate
      analysis an increase was observed in cardiovascular (odds ratio [OR] =2.81; 95%
      confidence interval [CI], 1.16-6.78), CVA (OR = 3.47; 95% CI, 1.19-10.07), and
      cardiac failure (OR = 6.75; 95% CI, 1.34-33.81), morbidity and mortality in
      diabetics with an ABI of < or = 0.90. CONCLUSIONS: The type 2 diabetics with PAD
      present with a higher morbidity and mortality. The ABI is a good predictor of
      cardiovascular disease and heart failure morbidity and mortality.

PMID- 16945272
TI  - [Peripheral arterial disease and usefulness of measuring the tibial/brachial
      index of diabetic patients].

PMID- 16945273
TI  - [Urinary tract infection by Candida species].
AB  - OBJECTIVES: To determine the frequency and characteristics of urinary tract
      infection (UTI) by Candida in diabetic patients (with and without symptoms) and
      to compare them with non-diabetic patients (with and without symptoms). DESIGN:
      Longitudinal, descriptive, and observational study. SETTING: Study conducted at
      the "Dr Ignacio Chavez" Clinic of family medicine, ISSSTE: Mexico. PARTICIPANTS:
      There were 2 kinds of patients; 1 with diabetes mellitus diagnosis (DM) with and
      without clinical picture of probable urinary tract infection (UTI), and 1 without
      DM and with and without clinical picture of probable UTI. MAIN MEASUREMENTS: A
      urine culture and a confidential questionnaire were administered to find the
      presence of urinary symptoms and likely risk factors associated with the
      infection. To associate these risks, the chi2 statistical method was used, with
      significance at 95% and Fisher's Exact Test for small frequencies, using the
      EpiInfo V.6.0 program. RESULTS: Two hundred thirty seven patients between 28 and
      82 years old were included. The prevalence of urinary infection by Candida was
      5.1%, but only 33% of these had C albicans. There was no association between
      candidiasis and factors like age, sex, or presence of DM, but it was related to
      previous treatments, previous UTI and the evolution time of DM. CONCLUSIONS: The
      conscious search by both doctor and laboratory for Candida micro-organisms as
      factors causing UTI is important. This is especially so in those patients with
      factors of risk that may condition Candida's presence.

PMID- 16945274
TI  - [Anxiety in adolescents of a Madrid neighbourhood].
AB  - OBJECTIVES: To determine the degree of state-trait anxiety in adolescents and its
      possible association with several socio-demographic variables. DESIGN:
      Descriptive cross-sectional study. SETTING: First semester of 2004. Two state
      secondary schools in Area 7, Madrid, Spain. PARTICIPANTS: Five hundred fifty nine
      students from the first to third years of secondary education. MAIN MEASUREMENTS:
      Two anonymous multiple-choice tests were given out to fill in during class time:
      STAIC (State-Trait Anxiety Inventory for Children) and a questionnaire of socio
      demographic variables (age, sex, immigration, toxic habits, socio-economic and
      family situation, relationships, view of life, and school results). RESULTS: Four
      hundred forty five tests were valid. Mean age, 13.8 (SD, 1.2); 53.5% were girls,
      18.7% immigrants, 20.7% took drugs (alcohol, tobacco, or illegal drugs), 32.8%
      had repeated at least 1 year, 14.3% considered their relationship with their
      family "bad," 15% referred to a "bad" relation with their class mates and 29.5%
      had a "bad" view of life. A statistically significant association was established
      between all these variables and anxiety. CONCLUSIONS: It is important to know
      what risk factors are associated with anxiety in order to detect it early and
      prevent its development to other serious mental disorders. In this study, higher
      levels of anxiety were found in immigrants, in girls, in drug users, in students
      in a worse socio-economic situation and in students who have had to repeat a
      year. This study corroborates the classic risk factors associated with anxiety,
      but shows that we should take into account a further one: immigration. It also
      suggests the importance of good family and personal relationships for
      psychological balance.

PMID- 16945275
TI  - [Appropriate use of benzodiazepines zolpidem and zopiclone in diseases attended
      in primary care].
AB  - OBJECTIVES: To estimate the proportion of benzodiazepine prescriptions that
      comply with the guidelines for appropriate prescription. To identify the
      variables associated with appropriate prescription. DESIGN: Observational, cross
      sectional study. SETTING: Monovar Health Centre in Area IV, Madrid, Spain.
      SUBJECTS: Random sample of 270 active benzodiazepine prescriptions in adult
      patients from the prescriptions record of the OMI-AP V. 5.0 computer system.
      MEASUREMENTS: The chosen dimensions for appropriate prescription were: a) correct
      diagnostic indication; b) absence of benzodiazepines with long half-life in the
      elderly; c) existence of support or monitoring visits; d) overall appropriateness
      or coexistence of correct diagnostic indications and monitoring visits.
      Independent variables were recorded in relation to patient, person prescribing
      and prescription. RESULTS: Diagnostic indication, 75.6%; absence of
      benzodiazepines with long half-life in the elderly, 79.8%; existence of support
      visits, 63.3%; overall appropriateness, 53%. Main diagnoses: pure anxiety, 29%;
      anxiety related to other illness, 18.6%; insomnia, 14.8%; cardiovascular illness,
      14.8%; alcohol and drug abuse, 4.5%; osteo-muscular illness, 4.4%; schizophrenia,
      4.4%. Most prescribed substances: lorazepam, 27.8%; bromazepam, 23.7%. Average
      life of prescriptions: 18.58 months. Origins: health centre, 68.5%; out-patient
      psychiatry, 10%; hospital, 10%. The variable that is most closely associated with
      overall appropriateness, fitted with the rest of the variables, is out-patient
      psychiatry prescription (OR, 6.67; 95% CI, 1.92-23.18). CONCLUSIONS: The mean
      duration of the prescriptions infringes all standards. The overall
      appropriateness or correct coexistence of adequate diagnostic indication with
      follow-up visits is associated with out-patient Psychiatry prescription.

PMID- 16945276
TI  - [The process by which family doctors manage uncertainty: Not everything is zebras
      or horses].

PMID- 16945277
TI  - [Protocol to evaluate the effectiveness of a consciousness-raising and training
      intervention for primary care professionals, in order to improve detection of
      domestic violence (ISFVIDAP)].
AB  - OBJECTIVE: To evaluate the effectiveness of an intervention aimed at primary care
      physicians and nurses to improve the detection of domestic violence. DESIGN:
      Community intervention study with control, randomized in clusters, pragmatic,
      open, and with parallel groups. SETTING: Primary care centres in Spain.
      POPULATION: Primary care physicians and nurses from the entire country who agree
      to participate in the study. UNIT OF ANALYSIS: The basic care team (BCT) of
      doctor and nurse looking after a list is the unit of analysis for evaluating the
      number of cases detected; and their clinical records are the units of analysis
      for evaluating recorded cases (suspicion and/or confirmation of mistreatment).
      SAMPLE SIZE: Sixty eight BCT in each group (136 in the 2 groups) and 1700
      clinical records per group (25 per BCT). Altogether, they will cover some 130,000
      women of 14 and over. INTERVENTION: A short training programme with homogeneous
      training contents, aimed at raising the awareness of health professionals and
      teaching them how to identify risk factors, situations of special vulnerability
      and alarm signals. The programme also aims to provide health professionals with
      tools to make the clinical interview easier, when they suspect mistreatment and
      how to tackle a case once it is detected. MEASUREMENTS: The main measurement will
      be the mean variation between intervention and control groups in the number of
      cases of domestic violence detected during the study, through specific recording
      and mean variation between the initial and final variations in each group.
      ANALYSIS: A weighted student's t test or, if covariates need to be adjusted, a
      regression analysis will be used for comparison. All analyses will be based on
      intention to treat.

PMID- 16945279
TI  - [Strategies to promote an egalitarian relationship with patients].

PMID- 16945278
TI  - [Consensus document on the use of antibiotics in primary care].

PMID- 16945280
TI  - [Allergy to tetanus toxoid: study of 14 cases].

PMID- 16945281
TI  - [Excess work-load of the main carers for dependent patients in primary care].

PMID- 16945282
TI  - [Oral bisphosphonates and musculoskeletal disorders].

PMID- 16945283
TI  - [In search of the lost trust in quality indicators].

PMID- 16945284
TI  - [EuroNeoStat. A European information system on the outcomes of care for extremely
      low birth-weight infants].

PMID- 16945285
TI  - [Obesity screening: updated criteria and their clinical and populational
      validity].
AB  - OBJECTIVES: The primary aim of this study was to compare the frequency of
      overweight and obesity in Spanish children and teenagers by using national and
      international standards for the body mass index (BMI). The second aim was to
      establish the association between criteria based on BMI and body composition. The
      third aim was to propose new standards of fat percentages in order to increase
      diagnostic accuracy in patients with excess weight. MATERIAL AND METHODS: The
      sample was composed of 7,228 boys and girls aged between 6 and 20 years.
      Anthropometric measurements were taken (height, weight and subcutaneous
      skinfolds), and BMI and the percentage of fat were obtained using the methods of
      Durnin and Womersley, Siri and Slaughter et al. To classify obesity and
      overweight, the national standards of Hernandez et al and the international
      standards published by Cole et al were used. The correlation between BMI and
      percentage of fat was established using Spearman's method and the variability fat
      percentage was estimated in relation to the BMI cut-off points proposed by the
      International Obesity Task Force (IOTF). RESULTS AND CONCLUSIONS: Overweight and
      obesity were more frequent in boys than in girls and in the youngest individuals.
      According to national standards, between 9.6 % (6-12 years) and 9.5 % (13-20
      years) of girls and between 10.62 % (13-20 years) and 12.50 % (6-12 years) of
      boys were overweight. According to international standards, between 4.68 % (13-20
      years) and 6 % (6-12 years) of boys were obese and between 18.83 % (13-20 years)
      and 21.6 % (6-12 years) were overweight. The proportion of obesity in girls
      ranged from 2.81 % (13-20 years) to 5.9 % (6-12 years); the prevalence of
      overweight was 25.99 % in the group aged 6-12 years and was 14.55 % in that aged
      13-20 years. The analysis carried out shows that the association between BMI and
      adiposity differs in normal individuals and in those with excess weight. The
      international standards of Cole et al tend to underestimate obesity and to
      overestimate overweight. Therefore, their usefulness is limited to comparative
      studies and their use cannot be recommended in clinical diagnosis, where it would
      be more effective to use of specific population standards, especially those for
      fat percentage.

PMID- 16945286
TI  - [Epidemiology of type 1 diabetes in children and adolescents aged less than 15
      years in the provinces of Castilla y Leon].
AB  - INTRODUCTION: The incidence of type 1 diabetes shows wide geographical
      variability and heterogeneity. The aim of this study was to determine the
      incidence and prevalence of type 1 diabetes in children and adolescents ages less
      than 15 years in the different provinces of Castilla-Leon. MATERIAL AND METHODS:
      To determine incidence, all new cases of type 1 diabetes with onset under 15
      years of age in 2003-2004 were obtained. Incidence was expressed as the crude
      value with the corresponding confidence interval and as standardized incidence.
      The capture-recapture method was used to calculate the completeness of
      ascertainment. To determine prevalence, all cases of type 1 diabetes in persons
      ages less than 15 years at 31 December 2004 were obtained. RESULTS: Incidence
      showed wide variability among the different provinces of Castilla-Leon. The
      highest values were found in Segovia (38.77/100,000/year), Valladolid
      (32.07/100,000/ year) and Avila (23.21/100,000/year) and the lowest in Zamora
      (8.14/100,000/year). Incidences were highest in the 5-9 years age group in all
      provinces except Burgos. Prevalence was highest in Segovia (1.54/1,000),
      Valladolid (1.41/1,000), Avila (1.38/1,000) and Zamora (1.32/1,000) and lowest in
      Burgos (0.91/1,000). CONCLUSIONS: Castilla-Leon seems to have one of the highest
      incidences of type 1 diabetes in Spain; several of its provinces have values
      similar to those in Northern Europe.

PMID- 16945287
TI  - [Congenital hyperinsulinism. Review of 22 cases].
AB  - INTRODUCTION: Congenital hyperinsulinism (CHI) is the most common cause of
      recurrent episodes of hypoglycemia in early childhood and consists of a group of
      distinct genetic disorders causing dysregulation of insulin secretion. OBJECTIVE:
      To review the presentation, management and outcome of patients with CHI attended
      at our hospital. MATERIAL AND METHODS: A retrospective review of all patients
      diagnosed with CHI between 1982 and 2004 was performed. Data were collected on
      age, gender, clinical presentation, medical and surgical management, and
      complications. RESULTS: Twenty-two patients were identified. Notable features
      were early symptom onset in 80 %, pancreatectomy in 72 %, and neurological
      sequels in 28 % (abnormal neurodevelopment in 22 % and epilepsy in 13 %).
      CONCLUSIONS: The presentation, management and outcome in our patients were
      similar to those in other series, indicating the need for early diagnosis and
      treatment to avoid neurological sequels.

PMID- 16945288
TI  - [Peritonsillar and retropharyngeal abscesses: study of 13 years].
AB  - INTRODUCTION: Peritonsillar and retropharyngeal abscesses are the most common
      deep head and neck infections. We present a series of patients with these
      infections. MATERIAL AND METHODS: We performed a retrospective study of
      peritonsillar and retropharyngeal abscesses in children admitted to the
      Infectious Diseases Unit of our hospital between January 1991 and January 2004.
      Diagnosis was based mainly on clinical and laboratory findings. RESULTS: We
      studied 54 patients, 10 with retropharyngeal abscess and 44 with peritonsillar
      abscess. The mean age was 6.7 and 7.5 years respectively. There was a slight
      predominance of boys (1.45:1). The number of cases diagnosed increased from 1997,
      with a maximum (nine cases) in 2002. Twenty-nine children had received previous
      antibiotic therapy. The main symptoms and signs were: fever, odynophagia,
      cervical lymphadenitis, and asymmetric tonsillar hypertrophy. All children
      received intravenous antibiotic therapy. Puncture-aspiration was carried out in
      seven patients. Eleven children underwent tonsillectomy, two with retropharyngeal
      abscess and nine with peritonsillar abscess. Of these 11 patients, five had had
      several episodes of tonsillitis and three had previously had a peritonsillar
      abscess. Three children who developed an abscess had previously undergone
      tonsillectomy. In most patients, outcome was favorable. CONCLUSIONS: In the last
      few years the frequency of peritonsillar and retropharyngeal abscesses has
      increased in the pediatric population. Most of the children have a good response
      to conservative treatment. The main risk factor for abscess recurrence is a
      previous history of repeated tonsillitis. Consequently, these patients are
      candidates for tonsillectomy.

PMID- 16945289
TI  - [Management of peritonsillar infections].
AB  - OBJECTIVE: To evaluate the clinical and epidemiologic characteristics in children
      with peritonsillar infections. PATIENTS AND METHODS: A longitudinal retrospective
      study was performed through a review of the clinical histories of patients
      attending the emergency unit in the previous 6 years. The variables gathered were
      age, sex, recurrent tonsillitis, previous upper airway infection, antibiotic
      administration, and therapeutic approach. RESULTS: Twenty-nine children were
      admitted, with a mean age of 7.4 +/- 1.6 years (boys 1.6:1). Twenty-seven percent
      had recurrent tonsillitis. At the visit, 57.8 % had an upper respiratory
      infection and 65 % were taking antibiotic treatment, especially macrolides. The
      treatment selected at our center consisted of the association of penicillin or
      amoxicillin-clavulanate acid with clindamycin, including corticosteroids. Ten
      children underwent computed tomography and nine underwent fine-needle aspiration.
      Drainage was performed in 20.6 % of confirmed abscesses. The mean length of
      hospital stay was 5.6 +/- 1.6 days. Delayed tonsillectomy was performed in 31 %,
      except in one patient who developed a parapharyngeal abscess. Currently, 18.9 %
      of all peritonsillar infections occur in the pediatric population. CONCLUSIONS:
      The increase in these infections is probably related to inappropriate use of
      antibiotics in respiratory diseases. Diagnosis is clinical, and infections are
      often resolved by intravenous administration of beta-lactams with clindamycin and
      an expectant attitude. When an abscess is suspected or there is no clinical
      improvement, fine-needle aspiration or computed tomography is warranted and
      drainage should be performed if an abscess is confirmed. Tonsillectomy, usually
      delayed, is only indicated in patients with recurrent tonsillitis.

PMID- 16945290
TI  - [Management of isolated minor head trauma. A multicenter study].
AB  - OBJECTIVE: To detect intracranial injuries (ICI) earlier in children with minor
      head trauma through the use of a previously established decision tree. METHOD: We
      performed a prospective multicenter study from September 2003 to January 2005.
      All patients aged between 3 months and 14 years old who visited the emergency
      department with minor head trauma (Glasgow Coma Scale score 13-15) were included.
      Six situations were established according to age (older or younger than 2 years)
      and low, intermediate or high risk for ICI. The management of each situation was
      suggested: observation at home, hospital observation or computed tomography (CT).
      The records of all patients were audited and categorized into: "properly
      classified, correct management", "properly classified but incorrect management",
      and "wrongly classified". All the patients were followed-up after discharge.
      RESULTS: A total of 2148 patients were included. Low risk was assigned to 54.8 %,
      intermediate risk to 32.4 %, and high risk to 12.8 %. Observation at home or in
      hospital was assigned to 53.4 % and 24 % respectively. CT was performed in 22.6
      %. ICI was detected in 1.6 % and 0.32 % required neurosurgery. There were 25 ICI
      in the high risk group, seven in the intermediate risk group, and none in the low
      risk group. No ICI were detected during follow-up. Most patients (90.1 %) were
      properly classified and the proposed management was carried out in 87.4 %.
      CONCLUSIONS: When the recommendations of the management protocol were applied,
      early detection of ICI was achieved in all the situations in which these lesions
      occurred.

PMID- 16945291
TI  - [Clinical practice guideline on asthma (part II)].

PMID- 16945292
TI  - [High-frequency oscillatory ventilation. A single-center study].
AB  - INTRODUCTION: High-frequency oscillatory ventilation is a safe and effective
      means of delivering mechanical ventilatory support. OBJECTIVE: To evaluate the
      safety and effectiveness of high-frequency oscillatory ventilation in pediatric
      patients with acute respiratory failure. PATIENTS AND METHOD: From August 2003 to
      July 2005, we performed a prospective observational study of 11 children older
      than 1 month who underwent high-frequency oscillatory ventilation. Pediatric risk
      of mortality scores (PRISM), Murray lung-injury scores and air leak scores were
      recorded at baseline before ventilation. The following variables were studied:
      ventilatory settings (FiO2 and mean airway pressure), gasometric (PaO2, SaO2,
      PaCO2, pHa, PaO2/FiO2 ratio) and hemodynamic parameters (Partm, PVC), and the
      oxygenation index. RESULTS: The overall survival rate was 82 %. Significant
      increases were found in PaO2 (p < 0.05), SaO2 (p < 0.05) and the PaO2/FiO2 ratio
      (p < 0.05), while mean airway pressure (p < 0.001), oxygenation index (p <
      0.001), and FiO2 (p < 0.001) significantly decreased over time. CONCLUSIONS: High
      frequency oscillatory ventilation significantly improved oxygenation in children
      with acute hypoxemic respiratory failure.

PMID- 16945293
TI  - [Crigler-Najjar syndrome: diagnosis and treatment].
AB  - INTRODUCTION: Crigler-Najjar syndrome (CNS) is a very rare disease characterized
      by severe indirect hyperbilirubinemia from birth with normal liver function. It
      may cause kernicterus at any age. This disease is due to a total or partial
      deficiency of the UDP-glucuronosyltransferase enzyme caused by a mutation of the
      five exons of the ULT1A1 gene. PATIENTS AND METHODS: We reviewed the clinical
      outcomes of 7 children diagnosed with CNS between 1987 and 2004. RESULTS: There
      were three boys and four girls (two of which were homozygote twins). Two children
      had familial consanguinity. Three out of the six families had another healthy
      child. The mean follow-up was 8.3 years (14 months-17 years). In all patients,
      jaundice was detected in the first 3 days of life. The children were admitted to
      hospital between the fourth and the sixtieth day of life with jaundice and
      indirect bilirubin levels of between 12.5 and 32 mg/dl. In all patients,
      hemolysis was ruled out and hepatic function was normal. The diagnosis was based
      on genetic study in 4 patients, on inactive UGT enzyme in liver in 1 patient, and
      on clinical features exclusively in 2 patients. Treatment consisted of
      phenobarbital and phototherapy from 8 to 16 hours a day in all patients except
      three. Associated calcium salts were found in 5 patients and cholestyramine was
      found in two. Two patients developed kernicterus. Two underwent liver
      transplantation and bilirubin levels became normal. The remaining patients
      maintained indirect bilirubin from 15 to 25 mg/dl with no associated neurological
      alterations. CONCLUSIONS: Patients with CNS are at greater risk of developing
      kernicterus, mostly associated with indirect bilirubin levels of around 25 mg/dl.
      Phototherapy is very useful in these patients but the only definitive treatment
      is liver transplantation.

PMID- 16945294
TI  - [Shwachman-Diamond syndrome. A case report].
AB  - Shwachman-Diamond syndrome is a rare autosomal recessive disorder characterized
      by exocrine pancreatic insufficiency, bone marrow dysfunction, skeletal
      abnormalities, and short stature. We describe the clinical characteristics,
      laboratory data, and treatment in a 14-month-old boy diagnosed with this syndrome
      in our unit.

PMID- 16945295
TI  - [Utility of bone scintigraphy in the differential diagnosis of child
      maltreatment].

PMID- 16945296
TI  - [Early application of high-frequency oscillatory ventilation in an infant with
      severe chemical neuropathy].

PMID- 16945297
TI  - [Effectiveness of rapid diagnostic techniques in two neonates with postnatal
      varicella].

PMID- 16945298
TI  - [Acute lithiasic cholecystitis as an exceptional presentation of celiac disease].

PMID- 16945299
TI  - [Auxologic study of girls adopted in China].

PMID- 16945300
TI  - [Hepatosplenomegaly and motor delay in a 6-month old infant].

PMID- 16945301
TI  - [The surgery to come: less vocation and changes in the form of teaching and
      practicing surgery].

PMID- 16945303
TI  - [Knowledge identification and management in a surgery department].
AB  - The hospital is an enterprise in which the surgery department represents a
      specific healthcare unit. The purpose of the surgery department, like that of any
      other enterprise, is assumed to be indefinite survival; to that end, it must be
      able to achieve and maintain a competitive advantage in the long term.
      Nevertheless, each surgery department, like each enterprise, can precisely define
      the scope of the above-mentioned terms, the main source of an enterprise's
      competitive advantage being its knowledge stock. Knowledge is recognized as being
      the basis of competitive success among institutions. This article presents the
      concept and classification of knowledge and discusses how it should be
      identified, inventoried, and managed. Special emphasis is placed on healthcare
      activity, since this sector presents certain characteristics distinguishing it
      from other sectors of economic and business activity.

PMID- 16945302
TI  - [Acute necrotizing pancreatitis: therapeutic alternatives].
AB  - The management of acute necrotizing pancreatitis has changed significantly over
      the last few years. Currently, most patients survive the early phases of the
      disease due to improvements in intensive care unit management. The most important
      risk factor for morbidity and mortality is infection of the pancreatic necrosis.
      Ideally, surgery should be delayed until 4 weeks after the onset of symptoms of
      pancreatitis, as it is at this time that the necrosis is most clearly demarcated.
      Advances in diagnostic imaging and minimally invasive techniques in surgery and
      radiology have revolutionized the surgical management of this disease. However,
      minimally invasive techniques should be limited to critically-ill patients unfit
      for conventional surgery.

PMID- 16945304
TI  - [Mortality analysis as a tool for quality improvement in a general surgery
      service].
AB  - OBJECTIVES: The present study aims to propose a method to improve healthcare
      quality based on systematic analysis of mortality and mortality-related adverse
      effects. PATIENTS AND METHODS: We analyzed all deaths in the surgery service
      between January, 1997 and December, 2003. There were 10,905 hospital admissions
      and 194 deaths. The mean number of deaths per year was 28 (range 24-36). The mean
      number of deaths/discharges per year was 1.77 (SD 0.2; range 1.5-2.13). The
      overall mean age was 80.5 years (SD 9.5; range 47-100). By sex there were 104
      women (53.6%) and 90 men (46.6%). During the study period 9,437 patients
      underwent surgery. We defined the concept of death secondary to a hospital
      problem (DSHP): this easily objectified concept includes any hospital problem
      occurring from admission to death associated directly or indirectly with death,
      or simply precipitating a foreseeable death. RESULTS: We detected 33 DSHP. Of all
      deaths, 17% were DSHP. In these DSHP, 37 problems were detected (some deaths
      involved more than one problem). The most frequent types of problem were three
      nosocomial infections, 19 problems secondary to therapeutic or diagnostic
      techniques, seven insufficient evaluations or treatment omissions or delays, and
      eight harmful incidents. No deaths occurred because of organizational or
      structural problems. The number of DSHP in relation to discharges was 0.3%.
      CONCLUSIONS: We present a system of continuous self-evaluation, in which problems
      are recognized and a constructive attitude is adopted. The model can be
      extrapolated to other hospitals but the results must be evaluated in the specific
      context of each hospital. Nevertheless, the results can be used for monitoring
      within a single center over a period of years.

PMID- 16945305
TI  - [Development and outcomes of the surgical management of multinodular goiter].
AB  - OBJECTIVES: The aims of this study were to: 1. Define our criteria and the
      results obtained in the surgical management of multinodular goiter (MNG); 2.
      Compare the results of partial thyroidectomies with those of total
      thyroidectomies; 3. Determine the incidence of "hidden" carcinomas diagnosed as
      MNG; 4. Define the most suitable treatment of MNG. MATERIAL AND METHODS: We
      performed a retrospective study (1999-2005) of 190 patients with MNG. Clinical
      characteristics, the diagnostic procedures used, surgical indications, the
      strategy employed, and biopsy results were analyzed. Overall morbidity and
      mortality were evaluated and statistical comparison of the morbidity-mortality
      rate between partial and total thyroidectomies was performed. RESULTS: Depending
      on the patients, diagnostic procedures consisted of ultrasonography, gammagraphy,
      computed tomography, and fine-needle aspiration (FNA). Surgical indication was
      established by compressive syndrome, endothoracic prolongation, rapid growth,
      suspected malignancy, nodular hyperthyroidism, the endocrinologist's criteria,
      and the patient's wishes. The surgical strategy showed a change in favor of
      radical surgery. The most common histologic diagnosis was nodular hyperplasia,
      but 16 carcinomas were "hidden" under a diagnosis of MNG (8.5%). There was no
      mortality. Morbidity, however, did exist, with the poorest results, showing
      statistically significant differences, occurring in total thyroidectomies.
      CONCLUSIONS: 1. Ultrasonography and FNA were routinely used for diagnosis.
      Surgical treatment tended to be radical. We believe that identification of
      recurrences and parathyroid disease is mandatory; 2. Morbidity was greater with
      total thyroidectomy; 3. Of patients who underwent surgery for MNG, 8.5% had a
      hidden thyroid carcinoma; 4. With certain limitations, total thyroidectomy is the
      most suitable therapy.

PMID- 16945306
TI  - [Factors associated with morbidity and mortality after gastric bypass.
      Alternatives for risk reduction: sleeve gastrectomy].
AB  - INTRODUCTION: The aim of this study was to analyze factors related to morbidity
      and mortality after gastric bypass and to evaluate lower-risk alternatives in
      selected patients. PATIENTS AND METHODS: A prospective cohort of 761 patients who
      underwent gastric bypass was included. Prognostic factors were studied using a
      logistic regression model with SPSS 11.0. Independent variables were age, sex,
      body mass index (BMI), comorbidities, and the laparoscopic approach. Dependent
      variables consisted of medical complications, surgical complications, and
      mortality. We performed a preliminary descriptive study of morbidity and weight
      loss at 3 months after sleeve gastrectomy. RESULTS: In the postoperative period,
      2.8% of patients presented medical complications and 5.4% presented surgical
      complications. Mortality was 0.52%. Surgical complications were significantly
      associated with age > 45 years (P = .04; OR = 2.00 [1.03-3.8]) and male sex (P =
      .041; OR = 2.40 [1.12-5.14]). Medical complications were significantly associated
      with a BMI of > 50 kg/m2 (P = .012; OR = 3.32 [1.23-8.98]), and mortality was
      significantly associated with a BMI of > 50 kg/m2 (P = .006) and male sex (P =
      .006). Sleeve gastrectomy was performed in eight patients with a BMI of > 60
      kg/m2, in three patients with a BMI of > 50 kg/m2, cardiopulmonary disease and
      android fat distribution, and in four patients with a BMI of between 35 and 40
      kg/m2 and major comorbidity. Morbidity consisted of self-limited febrile syndrome
      in one patient. There was no mortality. Weight loss at 3 months was 39.8 +/-
      5.36% of excess BMI in superobese patients (n = 4) and was 50.2 +/- 11.05% of
      excess BMI in morbidly obese patients (n = 4). CONCLUSIONS: Postoperative
      morbidity and mortality was significantly higher in male patients, in patients
      aged more than 45 years, and in those with a BMI of > 50 kg/m2. Sleeve
      gastrectomy in selected patients could be a lower-risk alternative.

PMID- 16945307
TI  - [Impact of the availability of an external nuclear medicine service in the
      application of sentinel lymph node biopsy in breast cancer surgery].
AB  - INTRODUCTION: To perform sentinel lymph node biopsy (SLNB), nuclear medicine
      services that have previously undergone a validation phase are required. The aim
      of the present study was to analyze the possibility of performing this technique
      with a previously validated, external nuclear medicine service and to study its
      impact on the indication for radical axillary lymphadenectomy (RAL) and on length
      of postoperative hospital stay. PATIENTS AND METHODS: We performed a prospective
      study in a cohort of patients with breast cancer starting from the introduction
      of SLNB in our center, which was made possible by collaboration with an external
      nuclear medicine service that performed lymphoscintigraphy and sentinel node
      detection. Intraoperative detection was performed through a portable probe. The
      feasibility of the project and its clinical impact were analyzed, taking a
      reduction in the number of lymphadenectomies and length of hospital stay as
      endpoints. RESULTS: A total of 196 patients with 201 breast carcinomas were
      treated. The most frequent interventions were tumorectomy (TC) with SLNB in 124
      patients (62%), and TC with SLNB and RAL in 62 patients (31%). Sentinel node
      visualization on lymphoscintigraphy was achieved in 187/201 carcinomas (93.1%)
      and sentinel nodes were detected during the intervention in 182/187 carcinomas
      (97.4%). Sentinel node detection in the internal mammary chain was achieved in
      23/201 carcinomas (11.4%). RAL was avoided in 131 of the 201 carcinomas (65%).
      Days of postoperative hospital stay with or without RAL showed a mean difference
      of 1.8 days (3.1 vs. 1.3; P < .001). CONCLUSION: SLNB is feasible with the
      collaboration of an external nuclear medicine service. This technique avoids 65%
      of RAL and reduces length of postoperative stay by 1.8 days.

PMID- 16945308
TI  - [Conceptual reformulation of the double mesh repair technique: a simple solution
      for highly complex abdominal wall defects].
AB  - INTRODUCTION: Repair of complex abdominal wall defects remains a challenge for
      the general surgeon. The aim of the present study was to validate the double mesh
      repair technique in complex hernias. MATERIAL AND METHOD: We performed a
      prospective study of 15 patients with complex abdominal wall defects who
      underwent surgery in a university hospital. All patients were evaluated in a
      multidisciplinary unit. Indications consisted of incisional hernias with multiple
      recurrences (> 3 times), prior mesh complicated by fistula and chronic infection,
      giant diffuse lumbar hernia, and ventral hernia (associated with parastomal
      hernia or occurring after bariatric surgery with associated dermolipectomy). The
      surgical technique used was double intra-abdominal and supra-aponeurotic mesh
      repair without associated plasty techniques. Clinical, surgical and follow-up
      data were analyzed. RESULTS: Nine defects were lateral, three were lumbar, one
      was parapubic, and two were located in the mid-line (one associated with giant
      parastomal hernia and one occurring after bariatric surgery). Eight showed
      significant tissue loss, five showed trophic skin lesions, and two showed chronic
      suppurative infection. The mean size of the defects was 17.5 cm. Seroma occurred
      in three patients and limited cutaneous necrosis occurred in one patient. The
      mean length of hospital stay was 4.3 days (range 2-7 days). No complications,
      recurrences or mortality were detected during follow-up. CONCLUSION: Complex
      abdominal wall defects can be corrected through double repair using mesh only.
      This technique is simple to learn and perform and can be applied in many
      anatomical sites and types of defect, as well as in the presence of tissue
      destruction.

PMID- 16945309
TI  - [Cephalic pancreaticoduodenectomy with mesentericoportal venous reconstruction.
      Technical features].
AB  - Cephalic pancreaticoduodenectomy (CPD) with mesentericoportal venous resection
      increases the resectability rate of pancreatic tumors. When performed in selected
      patients and by experienced surgical teams, this technique shows the same long
      term rates of morbidity, mortality and survival as CPD without vascular
      resection, provided that negative surgical margins are obtained. This procedure
      is contraindicated by complete thrombosis of the portal or superior mesenteric
      veins, invasion of the superior mesenteric artery or celiac trunk, and distant or
      periaortic lymph node involvement. Venous reconstruction can be performed through
      lateral suture, termino-terminal anastomosis, or by graft placement. We believe
      that intercalation of the autologous internal jugular vein facilitates resection
      and minimizes phenomena of venous stasis. We present a case of adenocarcinoma of
      the pancreatic head infiltrating the superior mesenteric-portal vein confluence
      that underwent surgery in our hospital. CPD with mesentericoportal venous
      resection and reconstruction using autologous internal jugular vein were
      performed. The most important technical features are discussed.

PMID- 16945310
TI  - [Endobronchial lipoma. Therapeutic considerations].
AB  - Endobronchial lipoma is a very rare benign tumor. The most frequent clinical
      presentation is caused by airway obstruction. A computed tomography finding of a
      homogeneous mass with fat density not enhanced by intravenous contrast material
      is considered diagnostic of this kind of tumor. The definitive diagnosis is given
      by bronchoscopy and biopsy. The treatment of choice is endoscopic resection,
      although open resection is sometimes required. We present a case of endobronchial
      lipoma that involved the left main bronchus and extended through the bronchial
      carina. Endoscopic treatment was initially attempted. However, open resection
      through superior lobectomy with carinal resection and a bronchoplastic procedure
      were required to avoid left pneumonectomy.

PMID- 16945311
TI  - [Hepatocarcinoma in noncirrhotic liver].
AB  - Hepatocellular carcinoma (HCC) usually develops in patients with liver cirrhosis
      or chronic liver disease. These tumors are highly infrequent in patients without
      precipitating factors. We present a series of four patients with nonfibrolamellar
      HCC arising in healthy liver. None of the patients had viral infection, or showed
      alcohol abuse and/or hemochromatosis. Three patients underwent surgery. The
      clinical characteristics, therapeutic options, and survival and recurrence rates
      in this type of tumor are discussed.

PMID- 16945312
TI  - [Image of the month. Intestinal perforation caused by foreign body].

PMID- 16945313
TI  - [Abdominal injury associated with inguinal hernia and orthopedic truss].

PMID- 16945314
TI  - [Pneumoretroperitoneum secondary to surgical lavage of a perianal abscess with
      hydrogen peroxide].

PMID- 16945315
TI  - [Spontaneous contralateral pneumothorax after pneumonectomy for bronchogenic
      carcinoma].

PMID- 16945316
TI  - Perceived stimulus complexity and food preference development.
AB  - The importance of perceived complexity, a "collative property" as defined by
      [Berlyne, D. E. (1967). Arousal and reinforcement. In Nebraska symposium on
      motivation (pp. 1-110). University of Nebraska Press], to the dynamic development
      of preference was investigated. Eighty-six female and 82 male subjects rated
      their liking for and various collative properties of seven very similar orange
      drinks that differed only in perceived complexity as a result of adding small
      quantities of other flavours. This was done before and after giving each subject
      extended experience of one of the drinks, each being used equally often for this
      purpose. As predicted by the theory of [Dember, W. N., & Earl, R. W. (1957).
      Analysis of exploratory, manipulatory and curiosity behavior. Psychological
      Review, 64 (2), 91-96] exposure to a stimulus with a slightly higher complexity
      than an individual subject's optimally preferred level of perceived complexity,
      caused an upwards shift in that level, whereas exposure to a less complex
      stimulus had no such effect. Changes in the appreciation of the drinks predicted
      by the theory were also observed.

PMID- 16945317
TI  - Memories affect mood: evidence from covert experimental assignment to positive,
      neutral, and negative memory recall.
AB  - Memory recall has been proposed as a common and effective mood regulation
      strategy. Although several studies have presented results suggesting that
      recalling valenced memories affects subsequent mood, their designs allow for
      alternative interpretations of the observed effects. Two such alternatives
      include the reverse effect (mood effects on memory due to non-experimental
      assignment to memory recall condition) and demand characteristics of the
      experiment. We used covert experimental assignment to memory condition, asking
      subjects (N=314; 56% female) to recall memories that were primarily positive,
      neutral, or negative. Results showed the expected effect on mood (p<.002), with
      reported mood worst in the negative memory condition, better in the neutral
      condition, and best in the positive condition. These results suggest that
      valenced memory recall does indeed exert an effect on mood, and may do so even
      without the individual's awareness.

PMID- 16945318
TI  - Folk knowledge about dengue mosquitoes and contributions of health belief model
      in dengue control promotion in Northeast Thailand.
AB  - The health belief model (HBM) has been adopted as the principal theory for health
      education and communication for dengue haemorrhagic fever (DHF) prevention and
      control in Thailand. The HBM focuses on persuading people to acknowledge their
      vulnerability and susceptibility to DHF, and the benefits of undertaking dengue
      larval control in household water containers. This study was undertaken in Khon
      Kaen province to investigate folk knowledge and beliefs about dengue mosquitoes
      and larval control campaigns and relating these to the theoretical components of
      HBM. Findings from this study indicate that health education messages can raise
      awareness during an outbreak but do not ensure sustained larval control
      practices. Several barriers are identified, including insufficient control
      agents, inadequate knowledge of control methods, and incompatibility of control
      practices with people's beliefs. The barriers prevail over the benefits of
      recommended larval control practices. In developing health education messages,
      consideration should go beyond the HBM and focus on control methods that are
      compatible with the socio-cultural environment in which control practices are
      being encouraged.

PMID- 16945319
TI  - Rapid time-resolved fluoroimmunoassay for diethylstilbestrol residues in chicken
      liver.
AB  - A competitive time-resolved fluoroimmunoassay (TR-FIA) was developed for the
      determination of diethylstilbestrol (DES) residues in chicken liver. Prior to
      analysis, the residues were extracted from chicken liver with acetonitrile. The
      assay could be used in a quantitative or qualitative mode. The limit of detection
      (LOD) was determined to be 0.05 ngg(-1), and the limit of quantification (LOQ)
      was less than 0.18 ngg(-1). The intraassay variations were less than 10%, and the
      interassay variations were from 9.8 to 12.7%. The mean recoveries established at
      six concentration levels varied from 84.3 to 109.6%, and the coefficients of
      variation were from 8.3 to 12.4%. The results obtained by the TR-FIA and enzyme
      linked immunosorbent assay (ELISA) showed a good correlation. The established TR
      FIA was validated for the determination of incurred chicken liver and was
      confirmed by liquid chromatography and tandem mass spectrometry (LC-MS/MS). This
      proposed technique could be applied to routine residue analysis.

PMID- 16945320
TI  - In situ phosphorylation of immobilized receptors on biosensor surfaces:
      application to E-cadherin/beta-catenin interactions.
AB  - Phosphorylation is a key posttranslational modification for modulating biological
      interactions. Biosensor technology is ideally suited for examining in real time
      the role of phosphorylation on protein-protein interactions in signaling
      pathways. We have developed processes for on-chip phosphorylation of immobilized
      receptors on biosensor surfaces. These processes have been used to analyze E
      cadherin/beta-catenin interactions. Phosphorylation of the intracellular domain
      (ICD) of E-cadherin modulates its affinity to beta-catenin and consequently the
      strength of cell-cell adhesion. We have phosphorylated immobilized E-cadherin ICD
      in situ using casein kinase 1 (CK1), casein kinase 2 (CK2), and src. On-chip
      phosphorylation of E-cadherin was confirmed using anti-phosphoserine and anti
      phosphotyrosine antibodies. The binding of beta-catenin to E-cadherin was
      analyzed quantitatively. CK1 phosphorylation of E-cadherin increased the binding
      affinity to beta-catenin from approximately 230 to 4 nM. A similar increase in
      affinity, from 260 to 4 nM, was obtained with CK2 phosphorylation of E-cadherin.
      However, phosphorylation by src kinase decreased the affinity constant from
      approximately 260 nM to 4 microM. Interestingly, phosphorylation of E-cadherin by
      CK1 or CK2 prevented the inhibition of beta-catenin binding by src
      phosphorylation.

PMID- 16945321
TI  - Concerted involvement of cooperative proton-electron linkage and water production
      in the proton pump of cytochrome c oxidase.
AB  - In cytochrome c oxidase, oxido-reductions of heme a/Cu(A) and heme a3/Cu(B) are
      cooperatively linked to proton transfer at acid/base groups in the enzyme. H+/e-
      cooperative linkage at Fe(a3)/Cu(B) is envisaged to be involved in proton pump
      mechanisms confined to the binuclear center. Models have also been proposed which
      involve a role in proton pumping of cooperative H+/e- linkage at heme a (and
      Cu(A)). Observations will be presented on: (i) proton consumption in the
      reduction of molecular oxygen to H2O in soluble bovine heart cytochrome c
      oxidase; (ii) proton release/uptake associated with anaerobic oxidation/reduction
      of heme a/Cu(A) and heme a3/Cu(B) in the soluble oxidase; (iii) H+ release in the
      external phase (i.e. H+ pumping) associated with the oxidative (R-->O
      transition), reductive (O-->R transition) and a full catalytic cycle (R-->O-->R
      transition) of membrane-reconstituted cytochrome c oxidase. A model is presented
      in which cooperative H+/e- linkage at heme a/Cu(A) and heme a3/Cu(B) with
      acid/base clusters, C1 and C2 respectively, and protonmotive steps of the
      reduction of O2 to water are involved in proton pumping.

PMID- 16945322
TI  - Assignment of a kinetic component to electron transfer between iron-sulfur
      clusters F(X) and F(A/B) of Photosystem I.
AB  - We studied the kinetics of reoxidation of the phylloquinones in Chlamydomonas
      reinhardtii Photosystem I using site-directed mutations in the PhQ(A)-binding
      site and of the residues serving as the axial ligand to ec3(A) and ec3(B)
      chlorophylls. In wild type PS I, these kinetics are biphasic, and mutations in
      the binding region of PhQ(A) induced a specific slowing down of the slow
      component. This slowing allowed detection of a previously unobserved 180-ns phase
      having spectral characteristics that differ from electron transfer between
      phylloquinones and F(X). The new kinetic phase thus reflects a different reaction
      that we ascribe to oxidation of F(X)(-) by the F(A/B) FeS clusters. These
      absorption changes partly account for the differences between the spectra
      associated with the two kinetic components assigned to phylloquinone reoxidation.
      In the mutant in which the axial ligand to ec3(A) (PsaA-Met688) was targeted,
      about 25% of charge separations ended in P(700)(+)A(0)(-) charge recombination;
      no such recombination was detected in the B-side symmetric mutant. Despite
      significant changes in the amplitude of the components ascribed to phylloquinone
      reoxidation in the two mutants, the overall nanosecond absorption changes were
      similar to the wild type. This suggests that these absorption changes are similar
      for the two different phylloquinones and that part of the differences between the
      decay-associated spectra of the two components reflect a contribution from
      different electron acceptors, i.e. from an inter-FeS cluster electron transfer.

PMID- 16945323
TI  - Interaction of sitamaquine with membrane lipids of Leishmania donovani
      promastigotes.
AB  - Sitamaquine is an 8-aminoquinoline which is active by the oral route for the
      treatment of life-threatening visceral leishmaniasis caused by Leishmania
      donovani, with an IC50 of 29.2 microM against the promastigote form in vitro. At
      high concentration (100 microM), sitamaquine affected parasite motility,
      morphology and growth in a way that was only partially reversible. As a first
      approach to determine its mechanism of action, we describe the interaction of
      sitamaquine with parasite membrane components, representing the first barrier to
      be crossed by the drug. Analysis of the physicochemical interactions of
      sitamaquine with monolayers of phospholipids and sterols at the air-water
      interface showed that these interactions only occurred in the presence of anionic
      phospholipids. Thus, electrostatic interactions between positively charged
      sitamaquine and the negative polar headgroups are a pre-requisite for subsequent
      hydrophobic interactions between the sitamaquine aromatic ring and the alkyl
      chains of phospholipids leading to drug insertion into the monolayer.

PMID- 16945325
TI  - The skin barrier in healthy and diseased state.
AB  - The primary function of the skin is to protect the body for unwanted influences
      from the environment. The main barrier of the skin is located in the outermost
      layer of the skin, the stratum corneum. The stratum corneum consists of
      corneocytes surrounded by lipid regions. As most drugs applied onto the skin
      permeate along the lipid domains, the lipid organization is considered to be very
      important for the skin barrier function. It is for this reason that the lipid
      organization has been investigated quite extensively. Due to the exceptional
      stratum corneum lipid composition, with long chain ceramides, free fatty acids
      and cholesterol as main lipid classes, the lipid organization is different from
      that of other biological membranes. In stratum corneum, two lamellar phases are
      present with repeat distances of approximately 6 and 13 nm. Moreover the lipids
      in the lamellar phases form predominantly crystalline lateral phases, but most
      probably a subpopulation of lipids forms a liquid phase. Diseased skin is often
      characterized by a reduced barrier function and an altered lipid composition and
      organization. In order to understand the aberrant lipid organization in diseased
      skin, information on the relation between lipid composition and organization is
      crucial. However, due to its complexity and inter-individual variability, the use
      of native stratum corneum does not allow detailed systematic studies. To
      circumvent this problem, mixtures prepared with stratum corneum lipids can be
      used. In this paper first the lipid organization in stratum corneum of normal and
      diseased skin is described. Then the role the various lipid classes play in
      stratum corneum lipid organization and barrier function has been discussed.
      Finally, the information on the role various lipid classes play in lipid phase
      behavior has been used to interpret the changes in lipid organization and barrier
      properties of diseased skin.

PMID- 16945324
TI  - Lack of enantiomeric specificity in the effects of anesthetic steroids on lipid
      bilayers.
AB  - The most important target protein for many anesthetics, including volatile and
      steroid anesthetics, appears to be the type A gamma-amino butyric acid receptor
      (GABA(A)R), yet direct binding remains to be demonstrated. Hypotheses of lipid
      mediated anesthesia suggest that lipid bilayer properties are changed by
      anesthetics and that this in turn affects the functions of proteins. While other
      data could equally well support direct or lipid-mediated action, enantiomeric
      specificity displayed by some anesthetics is not reflected in their interactions
      with lipids. In the present study, we studied the effects of two pairs of
      anesthetic steroid enantiomers on bilayers of several compositions, measuring
      potentially relevant physical properties. For one of the pairs, allopregnanolone
      and ent-allopregnanolone, the natural enantiomer is 300% more efficacious as an
      anesthetic, while for the other, pregnanolone and ent-pregnanolone, there is
      little difference in anesthetic potency. For each enantiomer pair, we could find
      no differences. This strongly favors the view that the effects of these
      anesthetics on lipid bilayers are not relevant for the main features of
      anesthesia. These steroids also provide tools to distinguish in general the
      direct binding of steroids to proteins from lipid-mediated effects.

PMID- 16945326
TI  - Transcriptional repression activity of PAX3 is modulated by competition between
      corepressor KAP1 and heterochromatin protein 1.
AB  - Pax3 is a transcription factor crucial for normal development and tumorigenesis.
      Pax3 has been known to cause Waardenburg syndrome and pediatric alveolar
      rhabdomyosarcoma, but how Pax3 regulates transcription is not clear. Here, we
      report that Pax3 represses transcription and selectively interacts with
      heterochromatin protein 1 (HP1) and KAP1. KAP1 functions as a transcriptional
      corepressor by recruiting HP1 to facilitate the formation of a closed chromatin
      through histone deacetylation and methylation. We found that KAP1 is a
      corepressor for Pax3 by augmenting the repressional activity of Pax3.
      Unexpectedly, HP1gamma diminishes the repressional activity of Pax3. On target
      promoters, KAP1 and HP1gamma compete for binding with Pax3 on the N-terminal
      paired domain, and the C-terminal domain of Pax3 governs the subcellular
      localization of Pax3. Taken together, our results indicate that Pax3 represses
      transcription through a novel mechanism involving competition between corepressor
      KAP1 and the heterochromatin-binding protein HP1gamma.

PMID- 16945327
TI  - Phenotypic screening of hepatocyte nuclear factor (HNF) 4-gamma receptor knockout
      mice.
AB  - Using the mouse as a model organism in pharmaceutical research presents unique
      advantages as its physiology in many ways resembles the human physiology, it also
      has a relatively short generation time, low breeding and maintenance costs, and
      is available in a wide variety of inbred strains. The ability to genetically
      modify mouse embryonic stem cells to generate mouse models that better mimic
      human disease is another advantage. In the present study, a comprehensive
      phenotypic screening protocol is applied to elucidate the phenotype of a novel
      mouse knockout model of hepatocyte nuclear factor (HNF) 4-gamma. HNF4-gamma is
      expressed in the kidneys, gut, pancreas, and testis. The first level of the
      screen is aimed at general health, morphologic appearance, normal cage behaviour,
      and gross neurological functions. The second level of the screen looks at
      metabolic characteristics and lung function. The third level of the screen
      investigates behaviour more in-depth and the fourth level consists of a thorough
      pathological characterisation, blood chemistry, haematology, and bone marrow
      analysis. When compared with littermate wild-type mice (HNF4-gamma(+/+)), the
      HNF4-gamma knockout (HNF4-gamma(-/-)) mice had lowered energy expenditure and
      locomotor activity during night time that resulted in a higher body weight
      despite having reduced intake of food and water. HNF4-gamma(-/-) mice were less
      inclined to build nest and were found to spend more time in a passive state
      during the forced swim test.

PMID- 16945328
TI  - Mutation at Glu23 eliminates the neuron growth inhibitory activity of human
      metallothionein-3.
AB  - Human metallothionein-3 (hMT3), first isolated and identified as a neuronal
      growth inhibitory factor (GIF), is a metalloprotein expressed predominantly in
      brain. However, until now, the exact mechanism of the bioactivity of hMT3 is
      still unknown. In order to study the influence of acid-base catalysis on S
      nitrosylation of hMT3, we constructed the E23K mutant of hMT3. During the course
      of bioassay, we found out unexpectedly that mutation at E23 of hMT3 eliminates
      the neuronal growth inhibitory activity completely. To the best of our knowledge,
      it is the first report that other residues, besides the TCPCP motif, in the beta
      domain can alter the bioactivity of hMT3. In order to figure out the causes for
      the loss of bioactivity of the E23K mutant, the biochemical properties were
      characterized by UV-vis spectroscopy, CD spectroscopy, pH titration, DTNB
      reaction, EDTA reaction, and SNOC reaction. All data demonstrated that stability
      of the metal-thiolate cluster and overall structure of the E23K mutant were not
      altered too much. However, the reaction of the E23K mutant with SNOC exhibited
      biphasic kinetics and the mutant protein released zinc ions much faster than hMT3
      in the initial step, while hMT3 exhibited single kinetic process. The 2D [1H-15N]
      HSQC was also employed to characterize structural changes during the reaction of
      hMT3 with varying mounts of nitric oxide. It was shown that the resonance of
      Glu23 disappeared at a molar ratio of NO to protein of 4. Based on these results,
      we suggest that mutation at Glu23 may alter the NO metabolism and/or affect zinc
      homeostasis in brain, thus altering the neuronal growth inhibitory activity.

PMID- 16945329
TI  - Phorbol ester potentiates the growth inhibitory effects of troglitazone via up
      regulation of PPARgamma in A549 cells.
AB  - The activation of peroxisome proliferator-activated receptor gamma (PPARgamma)
      has been shown to induce growth arrest and differentiation of various cancer
      cells. In the current study, we investigated the effect of 12-O
      tetradecanoylphorbol-13-acetate (TPA) on the expression of PPARgamma and
      proliferation of A549 cells. TPA elicited a dose- and time-dependent increase in
      PPARgamma mRNA and protein levels. PPARgamma expression in response to TPA was
      attenuated by pretreatment with bisindolylmaleimide I, N-acetyl-L-cysteine (NAC)
      and PD98059. TPA-induced protein kinase C (PKC) activation was linked to the
      generation of reactive oxygen species (ROS), both of which were indispensable for
      PPARgamma expression in A549 cells. Pretreatment with bisindolylmaleimide I or
      NAC blocked TPA-induced phosphorylation of extracellular signal-regulated kinase
      (ERK), suggesting that ERK-mediated signaling is also involved in the induction
      of PPARgamma. Furthermore, the growth inhibitory effect of troglitazone was
      significantly potentiated by prolonged incubation with TPA and was attenuated in
      the presence of GW9662, a specific inhibitor of PPARgamma. These effects were
      associated with an induction of cell cycle arrest at G0/G1 phase, which was
      accompanied by the induction of p21Waf1/Cip1 expression and decreased cyclin D1
      expression. Taken together, these observations indicate that TPA synergizes with
      PPARgamma ligand to inhibit cell growth through up-regulation of PPARgamma
      expression.

PMID- 16945330
TI  - Intradermal pregnenolone sulfate attenuates capsaicin-induced nociception in
      rats.
AB  - We have previously shown that the neurosteroid pregnenolone sulfate (PS) inhibits
      the capsaicin receptor-mediated current in rat dorsal root ganglion neurons.
      Here, we examined the effect of intradermal injection of PS into the rat hindpaw
      on capsaicin-induced nociception. Results revealed that PS co-injected with
      capsaicin dose-dependently inhibited the capsaicin-induced nocifensive response.
      In contrast, injections of PS into one hindpaw and capsaicin into the
      contralateral hindpaw had no effect on the capsaicin-induced nocifensive
      response, suggesting that PS produced its effect locally but not systemically.
      Moreover, PS inhibition of the capsaicin-induced nocifensive response was not
      significantly reduced by a nonselective opioid receptor antagonist or by
      cannabinoid receptor antagonists, indicating that neither an opioid- nor a
      cannabinoid-dependent mechanism mediated the effect of PS. These data demonstrate
      that PS acts peripherally to attenuate capsaicin-induced nociception through an
      opioid- and cannabinoid-independent mechanism and suggest a new therapeutic
      potential for PS in pain management.

PMID- 16945331
TI  - Solution structure of Ser14Gly-humanin, a potent rescue factor against neuronal
      cell death in Alzheimer's disease.
AB  - The NMR solution study of Ser14Gly-humanin (S14G-HN), a 1000-fold more potent
      derivative of humanin (HN), is reported. HN is 24-residue peptide that
      selectively suppresses neuronal cell death caused by Alzheimer's disease (AD)
      specific insults and offers hope for the development of a cure against AD. In
      aqueous solution the NMR data show that S14G-HN is a flexible peptide with turn
      like structures in its conformational ensemble distributed over an extensive part
      of its sequence from Pro3 to Glu15. In the more lipophilic environment of 30%
      TFE, an alpha-helical structure spanning residues Phe6 to Thr13 is identified.
      Comparison of these findings to the NMR structure of the parent HN and to
      existing structure-function relationship literature data outlines the important
      for activity structural features for this class of neuroprotective peptides, and
      brings forth flexibility as an important characteristic that may facilitate
      interactions with functional counterparts of the neuroprotection pathway.

PMID- 16945333
TI  - Design and mechanism of action of a novel bacteria-selective antimicrobial
      peptide from the cell-penetrating peptide Pep-1.
AB  - Here, we report the successful design of a novel bacteria-selective antimicrobial
      peptide, Pep-1-K (KKTWWKTWWTKWSQPKKKRKV). Pep-1-K was designed by replacing Glu
      2, Glu-6, and Glu-11 in the cell-penetrating peptide Pep-1 with Lys. Pep-1-K
      showed strong antibacterial activity against reference strains (MIC = 1-2 microM)
      of Gram-positive and Gram-negative bacteria as well as against clinical isolates
      (MIC = 1-8 microM) of methicillin-resistant Staphylococcus aureus and multidrug
      resistant Pseudomonas aeruginosa. In contrast, Pep-1-K did not cause hemolysis of
      human erythrocytes even at 200 microM. These results indicate that Pep-1-K may be
      a good candidate for antimicrobial drug development, especially as a topical
      agent against antibiotic-resistant microorganisms. Tryptophan fluorescence
      studies indicated that the lack of hemolytic activity of Pep-1-K correlated with
      its weak ability to penetrate zwitterionic phosphatidylcholine/cholesterol (10:1,
      w/w) vesicles, which mimic eukaryotic membranes. Furthermore, Pep-1-K caused
      little or no dye leakage from negatively charged
      phosphatidylethanolamine/phosphatidylglycerol (7:3, w/w) vesicles, which mimic
      bacterial membranes but had a potent ability to cause depolarization of the
      cytoplasmic membrane potential of intact S. aureus cells. These results suggested
      that Pep-1-K kills microorganisms by not the membrane-disrupting mode but the
      formation of small channels that permit transit of ions or protons but not
      molecules as large as calcein.

PMID- 16945332
TI  - Novel role of the RET finger protein in estrogen receptor-mediated transcription
      in MCF-7 cells.
AB  - The Scaffold attachment factor B1 (SAFB1) is an estrogen receptor (ESR1)
      repressor that has been proposed to inhibit breast tumorigenesis. To obtain
      insight into the functions of SAFB1 we utilized a yeast two-hybrid screen and
      identified the Ret finger protein (RFP) as interacting with the SAFB1 C-terminus.
      RFP is a member of the trimotif (TRIM) family of proteins, which we found widely
      expressed in a series of breast cancer cell lines. We confirmed the interaction
      between SAFB1 and RFP through in vitro (GST-pull-down) and in vivo
      (coimmunoprecipitations) assays. We hypothesized that SAFB1 functions as a
      scaffolding protein to recruit proteins such as RFP into proximity with ESR1.
      Consequently, we asked whether RFP would modulate ESR1 activity and we discovered
      that RFP was important for the ESR1-dependent expression of cyclin D1 (CCND1) and
      the progesterone receptor (PR), but not IRS1 or MYC. Although RFP did not
      interact with ESR1 directly, it does coimmunoprecipitate with ESR1, demonstrating
      that RFP is found within the same protein complex. Chromatin immunoprecipitation
      assays (ChIP) located RFP to the TFF1 promoter, a known ESR1-regulated gene.
      Taken together, our study provides further evidence that coactivation and
      corepression are integrally linked processes and that RFP is a component of an
      ESR1 regulatory complex.

PMID- 16945334
TI  - Rhes expression in pancreatic beta-cells is regulated by efaroxan in a calcium
      dependent process.
AB  - The monomeric G-protein Rhes has been described to be present in pancreatic beta
      cells, and a putative role in the control of insulin release has been proposed.
      Here, we show that treatment of beta-cells with the imidazoline insulin
      secretagogue efaroxan resulted in a concentration- and time-dependent increase in
      the expression of Rhes, which peaked after 4h of efaroxan exposure; thereafter,
      Rhes mRNA levels decreased. Marked stereoselectivity was displayed, with (-)
      efaroxan (the selectively insulinotropic enantiomer) being much more effective
      than (+)-efaroxan at raising Rhes transcript levels. The mechanism by which Rhes
      gene expression is activated in beta-cells appears to require the influx of
      extracellular calcium and de novo protein synthesis, and is not directly
      associated with the release of insulin. The present results confirm our earlier
      proposal that Rhes is an imidazoline-regulated transcript in pancreatic beta
      cells. Studies to understand the role of Rhes as a regulator of beta-cell
      function are, thus, warranted.

PMID- 16945335
TI  - Ribozyme-mediated selective killing of cancer cells expressing carcinoembryonic
      antigen RNA by targeted trans-splicing.
AB  - Carcinoembryonic antigen (CEA) has been shown to be involved in a variety of
      neoplasia process, such as tumor cell adhesion, metastasis, blocking of cellular
      immune mechanisms, and anti-apoptosis function. Therefore, CEA has been a
      potential target for anti-cancer therapy. In this study, we developed a specific
      ribozyme that can target CEA RNA and then reprogram the RNA with new transcripts,
      resulting in triggering of transgene activity selectively in cancer cells that
      express the RNA. The ribozyme-mediated induction of the transgene expression was
      caused via a highly accurate and specific RNA replacement through trans-splicing
      reaction with the targeted residue in the CEA-expressing cells. Simultaneously
      with the specific RNA replacement, the ribozyme efficiently reduced expression
      level of the targeted CEA RNA in the cells. Importantly, the ribozyme could
      selectively deliver activity of suicide gene, herpes simplex virus thymidine
      kinase gene, into cancer cells expressing the CEA RNA and thereby specifically
      retarded the survival of these cells with ganciclovir treatment. These suggest
      that the CEA RNA-targeting trans-splicing ribozyme could be a powerful genetic
      agent for specific cancer gene therapy.

PMID- 16945336
TI  - Expression of HSP72 in the gastric mucosa is regulated by gastric acid in rats
      correlation of HSP72 expression with mucosal protection.
AB  - BACKGROUND AND AIM: The real mechanism of adaptive cytoprotection in the gastric
      mucosa is not well established. In the present study, we investigated the effect
      of acid suppressing agents on a 72-kDa heat shock protein (HSP72) expression,
      which is known as endogenous cytoprotective factor, in the gastric mucosa. Also,
      the association of gastric mucosal protective function against HCl-challenge was
      compared between HSP72-induced and -reduced group. MATERIALS AND METHODS:
      Expression of HSP72 was measured by Western blotting in the gastric mucosa before
      and after administration of famotidine or omeprazole. The gastric mucosal
      protective function against 0.6 N HCl was compared between control group and
      HSP72-reduced group. Also, the effect of increased expression of gastric HSP72 by
      additional administration of zinc sulfate or zinc L-carnosine, which is known as
      HSP72-inducer, on mucosal protective function was studied. RESULTS: HSP72
      expression in the gastric mucosa was reduced by acid suppressing agents. The
      lowest expression level of HSP72 was observed 12 h (famotidine, H2-receptor
      antagonist) or 48 h (omeprazole, proton pump inhibitor) after administration. The
      gastric mucosal protective ability against 0.6 N HCl was also reduced when HSP72
      expression was decreased by famotidine or omeprazole. This phenomenon was
      reversed by HSP72 induction by additional administration of zinc derivatives.
      CONCLUSION: Our results might indicate that the expression of HSP72 in the
      gastric mucosa is physiologically regulated by gastric acid, and that HSP72
      induction could be important in view of mucosal protection especially when HSP72
      expression is reduced by administration of acid suppressing agents such as proton
      pump inhibitor or H2 receptor antagonist.

PMID- 16945337
TI  - Ketamine-induced cardiac depression is associated with increase in [Mg2+]i and
      activation of p38 MAP kinase and ERK 1/2 in guinea pig.
AB  - This study investigated the signaling pathways responsible for ketamine-induced
      cardiac depression in guinea pigs. The left ventricular development pressure
      (LVDP), velocity of the change in pressure (dP/dt), and heart rate (HR)
      accompanied with the total magnesium efflux ([Mg]e) were measured simultaneously
      in perfused hearts. The level of activation of the extracellular signal-regulated
      kinases 1/2 (ERK 1/2) and p38 mitogen-activated protein (MAP) kinase. The
      intracellular ionized magnesium concentration ([Mg2+]i) was measured using Mag
      fura 2 AM in a single cardiomyocyte. Ketamine produced reversible decreases in
      the LVDP, dP/dt, and HR accompanied by increases in the [Mg]e. Ketamine also
      produced significant activation of p38 MAP kinase and ERK 1/2, and produced a
      dose-dependent increase in the [Mg2+]i, which was inhibited SB203580 and PD98059.
      These results suggest that ketamine-induced cardiac depression can be partly
      responsible for the increase in [Mg2+]i and [Mg]e, accompanied by the activation
      of p38 MAP kinase and ERK 1/2 in guinea pigs.

PMID- 16945338
TI  - Verteporfin, photofrin II, and merocyanine 540 as PDT photosensitizers against
      melanoma cells.
AB  - The efficiency of photodynamic effect (PDE) for Photofrin II (PfII), Verteporfin,
      and Merocyanine 540 (MC540) was compared against neoplastic cells. Triplet state
      lifetimes and singlet molecular oxygen quantum yields were correlated with
      biological effect. PfII triplet lifetime was two times longer than that of
      Verteporfin, however, its singlet molecular oxygen quantum yield was two times
      lower in comparison with Verteporfin. High singlet molecular oxygen quantum yield
      of Verteporfin resulted in high biological efficacy. To achieve 50% mortality of
      cells four times lower light dose and five times lower concentration of
      Verteporfin were applied in comparison with PfII. The same level of cell damage
      was reached using 10 times higher light dose and two times higher concentration
      of MC540 in comparison with PfII. Our results confirm that singlet molecular
      oxygen based mechanism, prevalent for Verteporfin and PfII, was highly effective
      against melanoma cells. Verteporfin can be used at small doses with high cellular
      damage efficiency.

PMID- 16945339
TI  - Identification and characterization of Hedgehog modulator properties after
      functional coupling of Smoothened to G15.
AB  - The seven-transmembrane receptor Smoothened (Smo) transduces the signal initiated
      by Hedgehog (Hh) morphogen binding to the receptor Patched (Ptc). We have
      reinvestigated the pharmacological properties of reference molecules acting on
      the Hh pathway using various Hh responses and a novel functional assay based on
      the coexpression of Smo with the alpha subunit of the G15 protein in HEK293
      cells. The measurement of inositol phosphate (IP) accumulation shows that Smo has
      constitutive activity, a response blocked by Ptc which indicates a functional Hh
      receptor complex. Interestingly, the antagonists cyclopamine, Cur61414, and SANT
      1 display inverse agonist properties and the agonist SAG has no effect at the Smo
      induced IP response, but converts Ptc-mediated inactive forms of Smo into active
      ones. An oncogenic Smo mutant does not mediate an increase in IP response,
      presumably reflecting its inability to reach the cell membrane. These studies
      identify novel properties of molecules displaying potential interest in the
      treatment of various cancers and brain diseases, and demonstrate that Smo is
      capable of signaling through G15.

PMID- 16945340
TI  - Structure-based design of potent Grb2-SH2 domain antagonists not relying on
      phosphotyrosine mimics.
AB  - Development of Grb2-SH2 domain antagonists is considered to be an effective and
      non-cytotoxic strategy to develop new antiproliferative agents because of their
      potential to shut down the Ras signaling pathway. We developed a concise route
      for the efficient synthesis of G1TE analogs on solid phase. Using this route, a
      series of cyclic peptides that do not rely on phosphotyrosine or its mimics were
      designed and synthesized based upon the phage library-derived cyclopeptide, G1TE.
      Considering that Gly7 plays prominent roles for G1TE binding to the Grb2-SH2
      domain, we introduced different amino acids in the 7th position. The D-Ala7
      containing peptide 3 demonstrates improved binding affinity by adopting favorable
      conformation for protein binding. This can be rationalized by molecular modeling.
      The optimization at the Leu2 position was also studied, and the resulting
      cyclopeptides exhibited remarkably improved binding affinity. Based upon these
      global modifications, a highly potent peptide ligand 9 was discovered with a Kd =
      17 nM, evaluated by Biacore binding assay. This new analog is one of the most
      potent non-phosphorus-containing Grb2-SH2 antagonists reported to date. This
      potent peptidomimetic provides a new template for the development of non-pTyr
      containing Grb2-SH2 domain antagonists and acts as a chemotherapeutic lead for
      the treatment of erbB2-related cancer.

PMID- 16945341
TI  - Protective role of protein kinase C epsilon activation in ischemia-reperfusion
      arrhythmia.
AB  - PURPOSE: Ischemic heart disease carries an increased risk of malignant
      ventricular tachycardia (VT), fibrillation (VF), and sudden cardiac death.
      Protein kinase C (PKC) epsilon activation has been shown to improve the
      hemodynamics in hearts subjected to ischemia/reperfusion. However, very little is
      known about the role of epsilon PKC in reperfusion arrhythmias. Here we show that
      epsilon PKC activation is anti-arrhythmic and its inhibition is pro-arrhythmic.
      METHOD: Langendorff-perfused isolated hearts from epsilonPKC agonist (epsilonPKC
      activation), antagonist (epsilonPKC inhibition) transgenic (TG), and wild-type
      control mice were subjected to 30 min stabilization period, 10 min global
      ischemia, and 30 min reperfusion. Action potentials (APs) and calcium transients
      (CaiT) were recorded simultaneously at 37 degrees C using optical mapping
      techniques. The incidence of VT and VF was assessed during reperfusion. RESULTS:
      No VT/VF was seen in any group during the stabilization period in which hearts
      were perfused with Tyrode's solution. Upon reperfusion, 3 out of the 16 (19%)
      wild-type mice developed VT but no VF. In epsilonPKC antagonist group, in which
      epsilonPKC activity was downregulated, 10 out of 13 (76.9%) TG mice developed VT,
      of which six (46.2%) degenerated into sustained VF upon reperfusion.
      Interestingly, in epsilonPKC agonist mice, in which the activity of epsilonPKC
      was upregulated, no VF was observed and only 1 out of 12 mice showed only
      transient VT during reperfusion. During ischemia and reperfusion, CaiT decay was
      exceedingly slower in the antagonist mice compared to the other two groups.
      CONCLUSION: Moderate in vivo activation of epsilonPKC exerts beneficial
      antiarrhythmic effect vis-a-vis the lethal reperfusion arrhythmias. Abnormal CaiT
      decay may, in part, contribute to the high incidence of reperfusion arrhythmias
      in the antagonist mice. These findings have important implications for the
      development of PKC isozyme targeted therapeutics and subsequently for the
      treatment of ischemic heart diseases.

PMID- 16945342
TI  - Role of ventral striatal dopamine D1 receptor in cigarette craving.
AB  - BACKGROUND: Several theories of cigarette craving suggest that dopaminergic
      function in the ventral striatum plays an important role. The objective of this
      study was to determine correlations between craving-related brain activation and
      dopamine D1 receptor (D1R) binding in smokers. METHODS: Twelve smokers and 12
      nonsmoking controls underwent [(15)O]H(2)O-positron emission tomography
      activation study and D1R-binding study using [(11)C]SCH 23390, and the
      correlations between receptor binding and cue-induced regional cerebral blood
      flow (rCBF) changes were assessed. Consecutive D1R-binding changes were examined
      during a period of 6 months of postsmoking abstinence in five smokers. RESULTS:
      Cue-induced activation was observed in the left ventral striatum including the
      nucleus accumbens in smokers. D1R binding in the ventral striatum showed a
      negative relationship with cue-induced craving and rCBF changes. D1R binding was
      significantly low in smokers, and there was a trend of increase after smoking
      abstinence. CONCLUSIONS: D1R binding and cue-induced rCBF changes in the ventral
      striatum suggest the important role of D1R in this region in cigarette craving.

PMID- 16945343
TI  - A pilot study of antidepressant-induced mania in pediatric bipolar disorder:
      Characteristics, risk factors, and the serotonin transporter gene.
AB  - BACKGROUND: Antidepressant-induced mania (AIM) has been described in bipolar
      disorder (BD) and has been associated with the short-allele of the serotonin
      transporter gene (5-HTT). We wished to investigate the frequency of and risk
      factors for AIM in pediatric patients with or at high risk for BD. METHODS: Fifty
      two children and adolescents (30 with BD and 22 with subthreshold manic symptoms,
      15.1 +/- 3.4 years old), all with a parent with BD, were interviewed with their
      parents for manic/depressive symptoms occurring before and after past
      antidepressant treatment. The 47 subjects with serotonin reuptake inhibitor
      (SSRI) exposure were genotyped for the 5-HTT polymorphism. RESULTS: Fifty percent
      of subjects were AIM+ and 25.5% had new onset of suicidal ideation. The AIM+ and
      AIM- groups did not differ significantly in relation to allele (p = .36) or
      genotype (p = .53) frequencies of the 5-HTT polymorphism. The AIM+ subjects were
      more likely to have more comorbidities (3.2 vs. 2.4; p = .02) and be BD type I (p
      = .04) than AIM- subjects. CONCLUSIONS: Youth with or at high risk for BD may be
      particularly vulnerable to SSRI AIM and thus should be monitored if given SSRIs.
      In this preliminary study, we did not find that the 5-HTT polymorphism
      significantly influenced vulnerability to AIM.

PMID- 16945344
TI  - Saliva cortisol and response to dexamethasone in children of depressed parents.
AB  - BACKGROUND: Major depression (MDD) is heritable, and children of depressed
      parents are at higher risk for the development of depression. However, depression
      in a parent might also act as a stressor leading to increased activation of
      neuroendocrine stress circuits. To address this question we examined saliva
      cortisol in children whose parents have a history of MDD. METHODS: We recruited
      15 families with one parent with MDD (26 prepubertal children) and 16 control
      families without history of parental MDD (32 prepubertal children). All parents
      and children underwent Structured Clinical Interview for DSM-IV and Kiddie
      Schedule For Affective Disorders And Schizophrenia interviews, respectively.
      Families were asked to collect morning, afternoon, and bedtime saliva samples for
      4 days for 2 weeks. At bedtime of the 3rd day, dexamethasone was administered.
      Two doses, standard and low, were used in each family. RESULTS: The majority of
      children demonstrated no psychiatric diagnosis. Children with MDD parents showed
      higher cortisol basally and higher cortisol after both 25 mg and 5 mg
      dexamethasone. However, this effect occurred predominantly in children whose
      parents were currently depressed. There were strong correlations for cortisol
      between parents and children (r = 52 in depressed; r = 499 in control).
      CONCLUSIONS: Elevated cortisol and impaired feedback seemed to reflect an
      environmental effect of MDD in a parent.

PMID- 16945345
TI  - Functional magnetic resonance imaging study of cognitive control in the healthy
      relatives of schizophrenia patients.
AB  - BACKGROUND: The predisposition, or diathesis, to schizophrenia is highly
      heritable. The manner in which this genetic diathesis is manifest in the central
      nervous system is largely unknown, although healthy relatives of schizophrenia
      patients show executive processing deficits associated with prefrontal cortical
      impairments. METHODS: The current study evaluated brain activity in 21 healthy
      relatives of schizophrenia patients and 20 demographically similar control
      subjects during correct trials on a stimulus-response incompatibility task.
      During the first part of each trial, participants represented and maintained the
      instruction for that trial; during the second part, participants used the
      instruction either to make an automatic response or to overcome this prepotent
      response. RESULTS: Behaviorally, relatives were slower when overcoming the
      prepotent response. Analyses focused on the first part of the trial indicated
      that both groups showed activity in middle frontal (Brodmann areas 46 and 9) and
      anterior cingulate (Brodmann area 32) gyri. However, control subjects showed
      significantly greater activity in dorsal prefrontal cortex (Brodmann areas 9, 8,
      and 6) when preparing to overcome the prepotent response, whereas patients'
      relatives showed prefrontal activity later, when making the response.
      CONCLUSIONS: Using an event-related design showed distinct prefrontal brain
      abnormalities associated with the genetic diathesis to schizophrenia.

PMID- 16945347
TI  - A role for MAP kinase signaling in behavioral models of depression and
      antidepressant treatment.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) is upregulated in the
      hippocampus by antidepressant treatments, and centrally administered BDNF can
      produce antidepressant-like effects in rodent behavioral models of depression.
      BDNF-regulated signaling pathways are thus potential targets for investigation of
      antidepressant mechanisms. METHODS: We examined the effects of inhibition of MAPK
      kinase (MEK) in mouse behavioral models for depression including interactions
      with effects of antidepressant drugs. We also assessed the behavioral
      consequences of a heterozygous gene deletion for BDNF combined with MEK
      inhibition or stress. RESULTS: Acute administration of the MEK inhibitor PD184161
      produced depressive-like behavior. PD184161 blocked the antidepressant-like
      effects of desipramine and sertraline in the forced swim test and blocked the
      effects of desipramine in the tail suspension test. Heterozygous deletion of BDNF
      alone did not influence behavior in the forced swim test but resulted in a
      depressive phenotype when combined with a low-dose MEK inhibitor or stress
      exposure. CONCLUSIONS: We demonstrate that acute blockade of MAPK signaling
      produces a depressive-like phenotype and blocks behavioral actions of
      antidepressants. We also demonstrate in BDNF heterozygous knockout mice an
      example of a how a defined genetic alteration can confer vulnerability to a
      pharmacologic or environmental challenge resulting in a depressive behavioral
      phenotype.

PMID- 16945346
TI  - A new dimension of sensory dysfunction: stereopsis deficits in schizophrenia.
AB  - BACKGROUND: Schizophrenia is a neurocognitive disorder with a wide range of
      cognitive and sensory impairments. Early visual processing has been shown to be
      especially impaired. This article investigates the integrity of binocular depth
      perception (stereopsis) in schizophrenia. METHODS: Seventeen schizophrenia
      patients and 19 healthy control subjects were compared on the Graded Circles
      Stereo Test. Results of stereoacuity were compared between patients and control
      subjects using t test. RESULTS: Schizophrenia patients demonstrated significantly
      (p = .006) reduced stereoacuity (mean = 142 arcseconds) versus control subjects
      (mean = 55 arcseconds). At the normative level for adults, patients performed
      below chance. CONCLUSIONS: These findings demonstrate an impairment of binocular
      depth perception and further confirm deficits of early visual processing in
      schizophrenia. Findings are discussed in context of magnocellular/dorsal stream
      processing with implications for visual processing and cognitive deficits.

PMID- 16945348
TI  - Novelty seeking involved in mediating the association between the dopamine D4
      receptor gene exon III polymorphism and heavy drinking in male adolescents:
      results from a high-risk community sample.
AB  - BACKGROUND: Previous research suggests that personality traits, particularly
      novelty seeking (NS), increase the risk of substance abuse. One possible
      explanation to account for this association relates to common genetic factors.
      The aim of this study was to examine whether allelic variants of the dopamine D4
      receptor gene (DRD4) are associated with alcohol use in adolescents and to
      determine the extent to which these links are mediated by NS. METHODS: Three
      hundred three adolescents (144 male participants, 159 female participants,
      approximately 15 years old) from a high-risk community sample completed self
      report questionnaires measuring alcohol intake and temperament (Junior
      Temperament and Character Inventory [JTCI]). DNA was genotyped for the DRD4 exon
      III polymorphism. RESULTS: Male participants carrying the 7-repeat allele of DRD4
      drank higher maximum amounts of alcohol per occasion and had greater lifetime
      rates of heavy drinking than male participants without this allele. Higher levels
      of NS were associated with higher alcohol intake in both genders. Multiple
      regression analyses support the role of NS in mediating the relationship between
      DRD4 and heavy drinking in male adolescents but not in female adolescents.
      CONCLUSIONS: These findings extend previous work highlighting the significance of
      personality traits as a mediating factor between genetic susceptibility and
      substance use during the period of early experimental use.

PMID- 16945349
TI  - Altered central micro-opioid receptor binding after psychological trauma.
AB  - BACKGROUND: Functional neuroimaging studies have detected abnormal limbic and
      paralimbic activation to emotional probes in posttraumatic stress disorder
      (PTSD), but few studies have examined neurochemical mechanisms that underlie
      functional alterations in regional cerebral blood flow. The mu-opioid
      neurotransmitter system, implicated in responses to stress and suppression of
      pain, is distributed in and is thought to regulate the function of brain regions
      that are implicated in affective processing. METHODS: Here we examined the micro
      opioid system with positron emission tomography and the micro-opioid receptor
      selective radiotracer [11C] carfentanil in 16 male patients with PTSD and two non
      PTSD male control groups, with (n = 14) and without combat exposure (n = 15).
      Differences in micro-opioid receptor binding potential (BP2) were detected within
      discrete limbic and paralimbic regions. RESULTS: Relative to healthy controls,
      both trauma-exposed groups had lower micro-opioid receptor BP2 in extended
      amygdala, nucleus accumbens, and dorsal frontal and insular cortex but had higher
      BP2 in the orbitofrontal cortex. PTSD patients exhibited reduced BP2 in anterior
      cingulate cortex compared with both control groups. Micro-opioid receptor BP2 in
      combat-exposed subjects without PTSD was lower in the amygdala but higher in the
      orbitofrontal cortex compared with both PTSD patients and healthy controls.
      CONCLUSIONS: These findings differentiate the general response of the micro
      opioid system to trauma from more specific changes associated with PTSD.

PMID- 16945350
TI  - Antidepressant-like effects of the histone deacetylase inhibitor, sodium
      butyrate, in the mouse.
AB  - BACKGROUND: Chromatin remodeling, including changes in histone acetylation, might
      play a role in the pathophysiology and treatment of depression. We investigated
      whether the histone deacetylase inhibitor sodium butyrate (SB) administered as
      single drug or in combination with the selective serotonin reuptake inhibitor
      (SSRI) fluoxetine exerts antidepressant-like effects in mice. METHODS: Mice
      (C57BL/6J) received injections of SB, fluoxetine, or a combination of both drugs
      either acutely or chronically for a period of 28 days and were subjected to a
      battery of tests to measure anxiety and behavioral despair. Histone acetylation
      and expression of brain-derived neurotrophic factor (BDNF) were monitored in
      hippocampus and frontal cortex. RESULTS: Co-treatment with SB and fluoxetine
      resulted in a significant 20%-40% decrease in immobility scores in the tail
      suspension test (TST), a measure for behavioral despair, both acutely and
      chronically. In contrast, decreased immobility after single drug regimens was
      limited either to the acute (fluoxetine) or chronic (SB) paradigm. Systemic
      injection of SB induced short-lasting histone hyperacetylation in hippocampus and
      frontal cortex. Among the four treatment paradigms that resulted in improved
      immobility scores in the TST, three were associated with a transient, at least
      50% increase in BDNF transcript in frontal cortex, whereas changes in hippocampus
      were less consistent. CONCLUSIONS: The histone deacetylase inhibitor SB exerts
      antidepressant-like effects in the mouse. The therapeutic benefits and molecular
      actions of histone modifying drugs, including co-treatment with SSRIs and other
      newer generation antidepressant medications, warrant further exploration in
      experimental models.

PMID- 16945351
TI  - Evidence for reduced cerebellar volumes in trichotillomania.
AB  - BACKGROUND: Limited knowledge exists regarding the neurobiology of
      trichotillomania (TTM). Cerebellum (CBM) volumes were explored, given its role in
      complex, coordinated motor sequences. METHODS: Morphometric magnetic resonance
      imaging (MRI) scans were obtained for 14 female subjects with DSM-IV diagnoses of
      TTM and 12 age-, education-, and gender-matched normal control (NC) participants.
      Parcellation was performed utilizing a recently developed methodology to measure
      subterritory volumes of the CBM. Regions were defined based on knowledge of the
      structural and functional subunits of the CBM. RESULTS: As predicted, significant
      group differences were reported for CBM raw cortical volumes (p = .008) that
      survived correction for total brain volume (TBV; p = .037) and head circumference
      (HC; p = .011). A priori and post hoc group raw volume comparisons for CBM
      subterritories and functional clusters revealed many significant differences.
      However, most differences failed to withstand correction for total CBM volumes
      (TCV). Smaller volumes were consistently reported for the TTM versus NC cohorts.
      Total Massachusetts General Hospital Hair Pulling Scale (MGHHPS) scores were
      significantly inversely correlated with left primary sensorimotor cluster volumes
      (p = .008), with smaller volumes associated with more severe TTM symptoms.
      CONCLUSIONS: These findings implicate the CBM in the neurobiology of TTM, with
      reduced subterritory volumes reported for the TTM versus NC groups.

PMID- 16945352
TI  - Lack of paternal care affects synaptic development in the anterior cingulate
      cortex.
AB  - Exposure to enriched or impoverished environmental conditions, experience and
      learning are factors which influence brain development, and it has been shown
      that neonatal emotional experience significantly interferes with the synaptic
      development of higher associative forebrain areas. Here, we analyzed the impact
      of paternal care, i.e. the father's emotional contribution towards his offspring,
      on the synaptic development of the anterior cingulate cortex. Our light and
      electron microscopic comparison of biparentally raised control animals and
      animals which were raised in single-mother families revealed no significant
      differences in spine densities on the apical dendrites of layer II/III pyramidal
      neurons and of asymmetric and symmetric spine synapses. However, significantly
      reduced densities (-33%) of symmetric shaft synapses were found in layer II of
      the fatherless animals compared to controls. This finding indicates an imbalance
      between excitatory and inhibitory synapses in the anterior cingulate cortex of
      father-deprived animals. Our results query the general assumption that a father
      has less impact on the synaptic maturation of his offspring's brain than the
      mother.

PMID- 16945353
TI  - Cell-permeable cAMP analog suppresses 6-hydroxydopamine-induced apoptosis in PC12
      cells through the activation of the Akt pathway.
AB  - Although cAMP protects neuronal cells from various apoptotic stimulations, its
      mechanism is not fully elucidated. We report here the molecular mechanism of the
      6-hydroxydopamine (6-OHDA)-induced apoptosis of pheochromocytoma PC12 cells and
      its suppression by 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate
      (pCPT-cAMP), which is a membrane permeable cAMP analog. Treatment of PC12 cells
      with 6-OHDA resulted in the activation of caspases and apoptosis, as detected by
      chromatin condensation. 6-OHDA also induced superoxide generation, Bid cleavage
      and mitochondrial membrane depolarization. In addition, Akt phosphorylation that
      was favorable to cell survival was decreased and p38 MAPK phosphorylation was
      increased by 6-OHDA. PC12 cell apoptosis was inhibited by pCPT-cAMP, Z-VAD-fmk (a
      broad-range caspase inhibitor) and tiron (a superoxide scavenger), although PC12
      cell apoptosis was not inhibited by cyclosporine A (an inhibitor of mitochondrial
      membrane permeability transition). Moreover, pCPT-cAMP promoted Akt
      phosphorylation, but it did not prevent superoxide generation and mitochondrial
      membrane depolarization. Conversely, LY294002, an inhibitor of Akt upstream
      molecule PI3-kinase, enhanced 6-OHDA-induced apoptosis. These results indicated
      that the 6-OHDA-induced apoptosis of PC12 cells was initiated by superoxide
      generation followed by caspase cascade activation, which was associated with the
      suppressed Akt phosphorylation and increased p38 phosphorylation. It is likely
      that pCPT-cAMP prevented the 6-OHDA-induced apoptosis via activation of the PI3
      kinase/Akt pathway without any effect on superoxide generation or mitochondrial
      membrane depolarization.

PMID- 16945354
TI  - Dietary phytoestrogens enhance spatial memory and spine density in the
      hippocampus and prefrontal cortex of ovariectomized rats.
AB  - Long-term maintenance of ovariectomized rats (9 weeks) on chow containing high
      phytoestrogen levels (Purina LabDiet 5001) as compared to chow with minimal
      phytoestrogens (Harlan 2016 Teklad) was associated with better performance of the
      spatial memory task, object placement, increased dendritic spine density in CA1
      and prefrontal cortex pyramidal neurons, and higher uterine weights. Object
      recognition memory, anxiety on an elevated plus maze and body weight were
      unaffected by phytoestrogen levels in the diet.

PMID- 16945355
TI  - The electrophysiological correlate of contour integration is modulated by task
      demands.
AB  - Psychophysical studies demonstrated under which task conditions contour
      integration based on orientation cues succeeds or fails. We investigated how the
      electrophysiological correlate of contour integration is modulated by changes in
      task demands. In two experiments, event-related potentials (ERPs) were recorded.
      We presented open or nearly closed contours defined by Gabor elements embedded in
      a background of randomly oriented distracters. In experiment 1, randomly oriented
      Gabors preceded the test stimulus, while in experiment 2, the screen was blank
      before appearance of the test stimulus. Correct performance was above 96% for
      aligned and slightly misaligned contours but did not significantly differ from
      chance level for random orientations of the contour elements. Detectable contours
      elicited a negative shift over posterior recording sites. This effect started
      about 150 ms after stimulus onset but was delayed for more difficult contour
      integration. Presenting the stimulus after a random display elicited a frontal
      selection positivity (FSP). In both experiments, contours elicited a P3, which
      was larger for aligned compared to misaligned contours. Timing, duration and
      localisation of the negative enhancement were similar to both the texture
      segmentation VEP (tsVEP) and the selection negativity (SN). Our results indicate
      that contours are processed similar to textures and that decreasing saliency of
      detectable contours is compensated by increasing processing time which possibly
      results from increasing allocation of visual selective attention.

PMID- 16945356
TI  - Shear stress sustains atheroprotective endothelial KLF2 expression more potently
      than statins through mRNA stabilization.
AB  - OBJECTIVE: The transcription factor KLF2 is considered an important mediator of
      the anti-inflammatory and anti-thrombotic properties of the endothelium. KLF2 is
      absent from low-shear, atherosclerosis-prone sites of the vascular tree but is
      induced by HMG-CoA reductase inhibitors (statins) in vitro. We studied KLF2
      dependent induction of important determinants of the atheroprotective status of
      the endothelium to determine whether pharmacological intervention, e.g. by
      statins, can potentially replace shear stress. METHODS: Shear stress and statin
      effects in combination with TNF-alpha were determined in human umbilical vein
      endothelial cells by quantitative measurements of the steady-state levels and
      stability of mRNA for KLF2 and its downstream target genes thrombomodulin (TM)
      and endothelial nitric oxide synthase (eNOS). RESULTS: We demonstrate that
      prolonged shear stress has a potential that is superior to that of statins to
      induce the KLF2-dependent expression of eNOS and TM, especially in the presence
      of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). These
      effects can be attributed to the sustained stabilization of KLF2 mRNA by shear,
      leading to an increased KLF2 protein expression and concomitant strong induction
      of KLF2 downstream targets. The stabilization of KLF2 mRNA is demonstrated to be
      dependent on signaling involving phosphoinositide 3-kinase (PI3K). CONCLUSION:
      The stabilization of KLF2 steady-state levels, as induced by prolonged shear
      stress but not by statins, may be essential for sustaining the quiescent,
      atheroprotective status of the vascular endothelium under inflammatory
      conditions.

PMID- 16945357
TI  - Nutrition, physical activity, and cardiovascular disease: an update.
AB  - Many epidemiological studies have indicated a protective role for a diet rich in
      fruits and vegetables against the development and progression of cardiovascular
      disease (CVD), one of the leading causes of morbidity and mortality worldwide.
      Physical inactivity and unhealthy eating contribute to these conditions. This
      article assesses the scientific rationale of benefits of physical activity and
      good nutrition on CVD, especially on atherosclerosis-related diseases. Compelling
      evidence has accumulated on the role of oxidative stress in endothelial
      dysfunction and in the pathogenesis of CVD. Reduced nitric oxide (NO)
      bioavailability due to oxidative stress seems to be the common molecular disorder
      comprising stable atherosclerotic narrowing lesions. Energy expenditure of about
      1000 kcal (4200 kJ) per week (equivalent to walking 1 h 5 days a week) is
      associated with significant health benefits. Such benefits can be achieved
      through structured or nonstructured physical activity, accumulated throughout the
      day (even through short 10-min bouts) on most days of the week. Some prospective
      studies showed a direct inverse association between fruit and vegetable intake
      and the development of CVD incidents such as acute plaque rupture causing
      unstable angina or myocardial infarction and stroke. Many nutrients and
      phytochemicals in fruits and vegetables, including fiber, potassium, and folate,
      could be independently or jointly responsible for the apparent reduction in CVD
      risk. Novel findings and critical appraisal regarding antioxidants, dietary
      fibers, omega-3 polyunsaturated fatty acids (n-3 PUFAs), nutraceuticals,
      vitamins, and minerals, are presented here in support of the current dietary
      habits together with physical exercise recommendations for prevention and
      treatment of CVD.

PMID- 16945359
TI  - Membranes are not just rafts.
AB  - A new definition for lipid rafts was coined at the Keystone Symposium of Lipid
      Rafts and Cell Function based on recent advances in the field. The revised
      definition lumps all membrane heterogeneities that are not rafts into a single
      class of "non-raft". In this commentary, we suggest that "non-raft" domains
      encompass a variety of membrane heterogeneities and are quite diverse in
      composition and origin. A good starting point for the study of this diversity
      would be phospholipids with unsaturated acyl chains, which display little
      affinity for cholesterol; these lipids are abundant in membranes such as the
      endoplasmic reticulum and that may form their own macro- or microdomains.

PMID- 16945358
TI  - Age-, gender-, and species-dependent mutagenicity in T cells of mice and rats
      exposed by inhalation to 1,3-butadiene.
AB  - Experiments were performed: (i) to investigate potential age- and gender
      dependent differences in mutagenic responses in T cells following exposures of
      B6C3F1 mice and F344 rats by inhalation for 2 weeks to 0 or 1250 ppm butadiene
      (BD), and (ii) to determine if exposures for 2 weeks to 62.5 ppm BD produce a
      mutagenic effect in female rats. To evaluate the effect of age on mutagenic
      response, mutant manifestation curves for splenic T cells of female mice exposed
      at 8-9 weeks of age were defined by measuring Hprt mutant frequencies (MFs) at
      multiple time points after BD exposure using a T cell cloning assay and comparing
      the resulting mutagenic potency estimate (calculated as the difference of areas
      under the mutant manifestation curves of treated versus control animals) to that
      reported for female mice exposed to BD in the same fashion beginning at 4-5 weeks
      of age. The shapes of the mutant T cell manifestation curves for spleens were
      different [e.g., the maximum BD-induced MFs in older mice (8.0+/-1.0 [S.D.]x10(
      6)) and younger mice (17.8+/-6.1 x 10(-6)) were observed at 8 and 5 weeks post
      exposure, respectively], but the mutagenic burden was the same for both age
      groups. To assess the effect of gender on mutagenic response, female and male
      rodents were exposed to BD at 4-5 weeks of age and Hprt MFs were measured when
      maximum MFs are expected to occur post-exposure. The resulting data demonstrated
      that the pattern for mutagenic susceptibility from high-level BD exposure is
      female mice>male mice>female rats>male rats. Exposures of female rats to 62.5 ppm
      BD caused a minor but significant mutagenic response compared with controls
      (n=16/group; P=0.03). These results help explain part of the differing
      outcomes/interpretations of data in earlier Hprt mutation studies in BD-exposed
      rodents.

PMID- 16945360
TI  - Performance characteristics of 5 automated thyroglobulin autoantibody and thyroid
      peroxidase autoantibody assays.
AB  - BACKGROUND: Measurement of thyroid peroxidase autoantibodies (TPOAb) is useful in
      diagnosing patients with autoimmune thyroid disease. Measurement of thyroglobulin
      autoantibodies (TgAb) is used to detect potential interferences with
      thyroglobulin immunoassays and in limited situations for the diagnosis of
      autoimmune thyroid disease. METHODS: The limit of detection, imprecision,
      reference interval, method comparison and diagnostic concordance for the ADVIA
      Centaur, ARCHITECT i2000, AxSYM, Immulite 2000, Modular E170 (TPOAb only), and
      UniCel DxI 800 (TgAb only) methods were evaluated. The Advantage was used as the
      comparison method. RESULTS: Total imprecision ranged from 2.6% to 14.9% for TgAb
      and 2.1% to 15.8% for TPOAb. Passing-Bablok slopes ranged from 0.51 to 10.4
      (TgAb) and 1.05 to 7.12 (TPOAb) with correlation coefficients of 0.48 to 0.82
      (TgAb) and 0.66 to 0.78 (TPOAb). Assay cutoffs were adjusted using a common set
      of reference interval samples. Concordance with the Advantage assay using the new
      cutoffs was found to be improved and ranged from 68.5% to 84.7% (TgAb) and 77.5%
      to 84.7% (TPOAb). CONCLUSIONS: Although all assays generally performed well,
      assay concordance for a negative or positive result ranged from 54.2 to 84.7%.
      Quantitative agreement between methods was generally poor and methods could not
      be used interchangeably. Additional standardization efforts are required to
      improve inter-method agreement.

PMID- 16945361
TI  - Are the beta-adducin C1797T polymorphism and gamma-adducin A386G polymorphism
      associated with essential hypertension in Yi and Hani populations?

PMID- 16945362
TI  - Analytical performance of serum free light-chain assay during monitoring of
      patients with monoclonal light-chain diseases.
AB  - BACKGROUND: Measurement of serum free light chains (FLC) is useful for the
      diagnosis and monitoring of monoclonal light-chain diseases. It has been
      suggested that there will be widespread replacement of urine Bence Jones protein
      measurement by serum FLC assay. We report on our experience with the assay during
      monitoring of light-chain myeloma (LCMM) and AL amyloidosis (AL). METHODS: Serum
      FLC immunoassay, serum and/or urine protein electrophoresis and immunofixation
      were performed on serial samples during monitoring of LCMM. Recovery and
      immunoreactivity of FLC were tested by sample dilution. Assay precision was
      determined by repeat assay of samples over several reagent lots. RESULTS: In one
      of 23 patients with LCMM there was non-reaction of a monoclonal kappa FLC with
      some reagent lots and the assay did not indicate disease relapse. Samples showed
      non-linear, non-parallel immunoreactivity on dilution. Several tested monoclonal
      FLC gave lower values at the assay starting dilution compared with higher sample
      dilution and non-parallel dose-response curves. The median between-reagent lot
      variation for FLC measurement was 19-20% CV. CONCLUSIONS: Laboratory staff and
      clinicians need to be aware of the potential for non-reactivity of individual
      monoclonal FLC, and the effects of dilution and precision on FLC values and their
      interpretation.

PMID- 16945363
TI  - Mitochondrial distribution and microtubule organization in fertilized and cloned
      porcine embryos: implications for developmental potential.
AB  - Mitochondrial distribution and microtubule organization were examined in porcine
      oocytes after parthenogenesis, fertilization and somatic cell nuclear transfer
      (SCNT). Our results revealed that mitochondria are translocated from the oocyte's
      cortex to the perinuclear area by microtubules that either constitute the sperm
      aster in in vitro-fertilized (IVF) oocytes or originate from the donor cell
      centrosomes in SCNT oocytes. The ability to translocate mitochondria to the
      perinuclear area was lower in SCNT oocytes than in IVF oocytes. Sperm-induced
      activation rather than electrical activation of SCNT oocytes as well as the
      presence of the oocyte spindle enhanced perinuclear mitochondrial association
      with reconstructed nuclei, while removal of the oocyte spindle prior to sperm
      penetration decreased mitochondrial association with male pronuclei without
      having an apparent effect on microtubules. We conclude that factors derived from
      spermatozoa and oocyte spindles may affect the ability of zygotic microtubules to
      translocate mitochondria after IVF and SCNT in porcine oocytes. Mitochondrial
      association with pronuclei was positively related with embryo development after
      IVF. The reduced mitochondrial association with nuclei in SCNT oocytes may be one
      of the reasons for the low cloning efficiency which could be corrected by adding
      yet to be identified, sperm-derived factors that are normally present during
      physiological fertilization.

PMID- 16945364
TI  - Differential effects of hydroxyacetophenone analogues on the transcytotic
      vesicular pathway in rat liver.
AB  - Insertion of transporter proteins into the apical canalicular membrane via
      vesicular transport is one of several choleretic mechanisms. Based on different
      choleretic activities of hydroxyacetophenone analogues including 4-mono; 2,6-di
      and 2,4,6-trihydroxy-acetophenone (MHA, DHA and THA), the present study aims to
      determine if these compounds stimulated vesicular transport in hepatocytes.
      Hydroxyacetophenone was continuously infused into the duodenum of the bile
      fistula rat. Bile flow rate was allowed to stabilize and then followed by an
      intraportal injection of horseradish peroxidase, a marker of the transcytotic
      vesicle pathway. MHA which stimulates bile acid independent flow, showed a dose
      dependent increase in both the early (paracellular) and late (transcellular) peak
      of horseradish peroxidase excretion in bile. THA, which stimulates both bile acid
      dependent flow and bile acid independent flow, did not alter the pattern of
      horseradish peroxidase excretion into bile. However, DHA, which is more
      hydrophobic and increases only bile acid dependent flow, decreased the late peak.
      The stimulating effects of MHA on bile flow and horseradish peroxidase excretion
      were markedly inhibited by colchicine, suggesting that its choleretic action
      involves stimulation of exocytosis, as well as increase in paracellular
      permeability. In contrast, the lack of a stimulatory effect of THA and DHA on
      biliary horseradish peroxidase excretion suggested that their choleretic action
      is not associated with vesicular exocytosis. These results demonstrate a variable
      effect of hydroxyacetophenones on the transcytotic vesicular pathway reflecting
      different choleretic mechanisms and therapeutic potential.

PMID- 16945365
TI  - Fe(III) improves antioxidant and cytoprotecting activities of mangiferin.
AB  - Iron-induced oxidative stress has been implicated in several pathological
      processes. In the present work we provide evidence for the formation of a
      mangiferin:Fe(III) complex (2:1), shown by means of either iron-induced changes
      in the UV/visible spectrum of mangiferin or by reduction of the anodic current
      peak in the voltammogram of that compound; we demonstrate, in addition, that the
      ferric complex is more effective than mangiferin itself in scavenging superoxide
      radicals generated by pyrogallol autoxidation, as well as in protecting
      hepatocytes from reactive oxygen species mediated hypoxia/reoxygenation injury.
      Moreover, we found that the mangiferin:Fe(III) complex reacts more readily with
      horseradish peroxidase/H(2)O(2) than does mangiferin by itself. We postulate that
      mangiferin could afford protection against iron/reactive oxygen species-mediated
      pathological processes by means of both iron chelating and iron-stimulated
      superoxide radical scavenging activity.

PMID- 16945366
TI  - Inhibition of dipeptidyl peptidase-IV activity by metformin enhances the
      antidiabetic effects of glucagon-like peptide-1.
AB  - GLP-1 and GIP are insulin-releasing 'incretin' hormones inactivated following
      degradation by dipeptidyl peptidase IV. Incretin hormone analogues resistant to
      degradation by DPP IV, as well as, inhibitors of DPP IV are in development as
      novel treatments for type 2 diabetes. The biguanide metformin is an oral agent
      commonly prescribed to treat type 2 diabetes. Antidiabetic actions of metformin
      involve the reduction of hepatic glucose production and/or insulin resistance.
      Recent reports indicate that metformin may have the additional property of
      inhibiting DPP IV activity. Here we examine the effects of metformin on plasma
      DPP IV activity of normal and ob/ob diabetic mice. DPP IV activity present in
      mouse plasma was concentration-dependently inhibited by metformin generating
      IC(50) values of 38 microM for normal mice and 29 microM for ob/ob mice. In vivo
      metformin lowered plasma DPP IV activity in ob/ob mice, and improved glucose
      lowering and insulin-releasing effects of exogenous GLP-1 administration. This
      was associated with increased circulating concentrations of active GLP-1(7
      36)amide. In contrast metformin had minor effects on in vitro GLP-1-stimulated
      insulin release from clonal beta cells. Long-term (12 day) oral metformin
      administration to ob/ob mice resulted in lower DPP IV activity but had no effect
      on basal glucose and insulin levels. These findings indicate that metformin
      decreases the plasma DPP IV activity, limiting the inactivation of exogenously
      administered GLP-1 and improving glycaemic control.

PMID- 16945367
TI  - Mu and kappa opioid receptor agonists antagonize icilin-induced wet-dog shaking
      in rats.
AB  - Icilin is a cooling agent that precipitates vigorous wet-dog shakes in rats after
      acute i.p. administration. Recent research has emphasized the peripheral agonist
      properties (e.g. activation of transient receptor potential channels, TRPM8 and
      TRPA1) of icilin rather than its unusual and pronounced behavioral effects, often
      classified as quasi-morphine withdrawal. We tested selective opioid receptor
      agonists against icilin-induced wet-dog shakes in rats. Shaking was antagonized
      following s.c. pretreatment with the mu agonists, morphine (1, 2, 3 mg/kg) and
      buprenorphine (0.10 mg/kg) or the kappa agonists, nalfurafine (0.02, 0.04 mg/kg)
      and U50,488H (5 mg/kg). Pretreatment with ICI 204,448 (1, 5, 10 mg/kg), the
      peripherally directed kappa agonist, or the delta agonist, SNC 80 (0.30, 1, 3, 10
      mg/kg), had no marked effect on the incidence of shaking. We conclude that (a)
      icilin can trigger shaking via interactions within the central nervous system and
      (b) mu and kappa opioid receptors are involved in suppressing this stimulant
      behavior.

PMID- 16945368
TI  - LPS from Escherichia coli protects against indomethacin-induced gastropathy in
      rats--role of ATP-sensitive potassium channels.
AB  - The effect of lipopolysaccharide (LPS) in gastric protection has not been
      elucidated, but ATP-sensitive potassium (K(ATP)) channels are known to be
      involved in gastric defense. We evaluated the effect of LPS administration on
      indomethacin-induced gastropathy, and the role of K(ATP) channels in this event.
      Rats received intravenous (i.v.) LPS administration. After 1/2, 6, 24 or 48 h,
      indomethacin was injected. 3H later, gastric damage and myeloperoxidase activity
      were determined. Another group received LPS and 5 h later, glibenclamide,
      diazoxide or glibenclamide plus diazoxide. After 1 h, the rats received
      indomethacin and 3 h later, gastric damage and myeloperoxidase activity were
      evaluated. LPS reduced dose dependently gastric damage and myeloperoxidase
      activity induced by indomethacin. Glibenclamide reversed this LPS effect on
      indomethacin-induced gastropathy. Glibenclamide plus diazoxide administration did
      not change this LPS effect. Thus LPS has a protective effect against indomethacin
      induced gastropathy, probably through activation of K(ATP) channels.

PMID- 16945369
TI  - The role of the IGF-I system for vitellogenesis in maturing female sterlet,
      Acipenser ruthenus Linnaeus, 1758.
AB  - Transition from previtellogeneic to vitellogenic oocyte growth is a critical
      phase for folliculogenesis in sturgeon and may often be postponed for several
      years. Recent findings on the involvement of insulin-like growth factor I (IGF-I)
      in cell differentiation processes of oocyte follicle and ovarian steroidogenesis
      of teleosts in vitro led to the hypothesis that paracrine IGF-I could function as
      a potential trigger in vivo. For the first time, IGF-I and its corresponding
      receptor (IGF-IR) were identified in a non-teleostean fish. Real-time PCR assays
      for IGF-I and IGF-IR mRNA were established, normalising mRNA expression of the
      target genes to beta-microglobulin (beta2m). We clearly show that expression of
      IGF-I in the gonad is a substantial source for IGF-I-mediated effects in
      follicles compared to liver, brain, muscle and adipose tissue. Among these
      tissues, IGF-IR mRNA was highest in the gonad. With regard to different cohorts
      of coexisting follicles, highest expression of IGF-I and IGF-IR were met in
      developing follicles, indicating that IGF-I functions as an intraovarian
      modulator of follicle faith. Comparing previtellogenic follicles in females that
      matured within two years with non-maturing females f the same age, revealed an
      increases of 2.3-fold for IGF-I and 2.8-fold for IGF-IR mRNA expression in
      maturing females. These findings implicate an important role of paracrine IGF-I
      in early vitellogenesis and identify it as candidate vitellogenesis inducing
      factor (VIF), determining the faith of the follicle.

PMID- 16945370
TI  - Operative treatment of acute Achilles tendon ruptures: an institutional review of
      clinical outcomes.
AB  - PURPOSE: To retrospectively review the clinical outcome and incidence of post
      operative complications after open end-to-end repair of acute Achilles tendon
      ruptures. METHODS: Seventy consecutive patients (74 open Achilles tendon repairs)
      operated on between 1989 and 2002 were identified for inclusion in this
      investigation. The medical records were reviewed and patients were contacted for
      a follow up interview in order to survey their post-operative function. Outcome
      scores were calculated based on the Boyden outcome and AOFAS ankle-hindfoot
      scoring systems. Post-operative complications were documented during the chart
      review and follow up interview, including an additional nine patients (nine
      repairs), who were not included in the clinical evaluation portion of the study.
      RESULTS: Fifty-two patients (54 repairs) were successfully contacted and
      completed the follow up interview. Within this cohort there were 44 males and 8
      females with a mean age of 41 years. Achilles tendon rupture in this population
      was attributable to participation in athletic activity in 87% of cases. At a mean
      post-operative follow up of 45 months, 96% of cases achieved an overall Boyden
      outcome score of good to excellent. The mean AOFAS ankle-hindfoot score was 96,
      with 74% of cases scoring greater than 90. Forty-two cases (78%) reported no pain
      and 40 cases (74%) reported no activity limitations. Fourteen post-operative
      complications were identified after 83 open Achilles tendon repairs, resulting in
      an institutional complication rate of 16.8%. The complications included four
      superficial wound infections, five deep wound infections requiring irrigation and
      debridement, one heel ulcer secondary to post-operative boot wear, three partial
      Achilles tendon re-ruptures, and one complete Achilles tendon re-rupture.
      CONCLUSION: Our results demonstrate that open end-to-end repair of acute Achilles
      tendon ruptures provides long-term functional outcomes with consistent good to
      excellent results. However, this high clinical success rate was associated with a
      relatively high incidence of post-operative complications. With careful attention
      to the surgical wound and patient adherence to post-operative rehabilitation
      protocols, operative repair of acute Achilles tendon ruptures is a reliable
      treatment for active patients.

PMID- 16945371
TI  - Vibrio infection associated with finning injury of the hand.
AB  - BACKGROUND: Penetrating injury by fish fins is common and often overlooked.
      Vibrio spp. are known worldwide for their virulence, quickly causing soft-tissue
      infection and lethal septicaemia. Vibrio infection following finning injury is
      rare, but can result in devastating complications in susceptible individuals.
      AIM: To elucidate the clinical significance of such injury. METHOD: Between July
      2003 and September 2005, nine cases of Vibrio infection caused by finning injury
      to the hand were retrospectively reviewed. Clinical data, including skin
      presentations, treatment course and outcomes, were collected and reviewed.
      RESULTS: In our group of nine patients, seven had concurrent hepatoma, diabetes
      mellitus, cirrhosis, chronic renal insufficiency or the effects of long-term
      steroid use; three had wound infections manifested by cellulitis or tenosynovitis
      and six had life-threatening necrotising soft-tissue infections. Vibrio spp. were
      identified from the wound (n=4), blood (n=1), and both (n=4). Symptoms appeared
      within a few hours to 3 days after injury, with 50% of patients developing
      symptoms within 24h; three patients were hypotensive upon admission; one patient
      received antibiotic therapy only and eight required emergency fasciotomy. All
      patients survived and none required amputation. The mean hospital stay was 23.2
      days. CONCLUSIONS: Vibrio infections after finning injury can produce bacteraemic
      necrotising soft tissue-infections, especially in individuals with a systemic
      illness. Health education should include a recommendation to wear protective
      gloves while handling fish. Early antibiotic and surgical treatment can avoid
      potentially life-threatening complications.

PMID- 16945372
TI  - What is the lifetime risk of contact with an A&E Department or an Institute of
      Forensic Medicine following violent victimisation?
AB  - OBJECTIVE: The aim of the study was to estimate the age and gender specific
      incidence rates of first time contact with an A&E Department and/or an Institute
      of Forensic Medicine due to violent victimisation in a Danish low-risk urban
      population and, secondly to estimate the corresponding lifetime risk of violence
      based upon these incidence rates. METHODS: All first time contacts of victims of
      violence with the A&E Department at Odense University Hospital and/or the
      Institute of Forensic Medicine, University of Southern Denmark 1991-2002 were
      included. Based on estimated age and gender specific annual incidence rates of
      first time violence and on the survival rates of the background population, the
      lifetime risk was estimated assuming calendar time stationarity of incidence and
      survival rates. RESULTS: The overall annual incidence rate of first time violence
      was 9.2 [95% CI: 9.0-9.4] per 1000 population/year for males and 2.6 [95% CI: 2.5
      2.7] per 1000 population/year for females. The estimated lifetime risk was 0.440
      [95% CI: 0.438-0.442] for males and 0.180 [95% CI: 0.178-0.181] for females. The
      highest cumulative risk for both males and females was in the age group 15-24
      years, 0.192 [95% CI: 0.188-0.195] for males and 0.048 [95% CI: 0.046-0.051] for
      females. CONCLUSION: The current study shows, that even in a country with a
      relatively low risk of violent victimisation a considerable part of the
      population over a lifetime will need medical assistance after violent
      victimisation.

PMID- 16945373
TI  - Codon 54 polymorphism of the fatty acid binding protein (FABP) 2 gene is
      associated with increased cardiovascular risk in the dyslipidemic diabetic
      participants of the Veterans Affairs HDL intervention trial (VA-HIT).
AB  - The threonine (Thr) for alanine (Ala) codon 54 polymorphism of the fatty acid
      binding protein (FABP) 2 gene, when compared to the wild type, is associated with
      dyslipidemia. Since dyslipidemia is common in diabetes and is associated with
      increased cardiovascular risk, we tested the hypothesis that Thr-54 is associated
      with increased cardiovascular risk in patients with diabetes. The secondary
      prevention veterans affairs HDL intervention trial (VA-HIT) was carried out in
      patients with dyslipidemia. The DNA of trial participants (n=776) was screened
      for the Thr-54 polymorphism and cardiovascular endpoints were monitored. The
      polymorphism was detected in 370 (47.7%). For first occurrence of the primary
      endpoint [myocardial infarction (MI) or coronary heart disease (CHD) death] the
      hazard ratio (HR) and confidence intervals (Cox proportional hazards model) was
      2.5 (1.2, 5.3) p=.02 in diabetic carriers of Thr-54 versus carriers without
      diabetes or fasting glucose >7 mmol/L. For the expanded endpoint (stroke, MI or
      CHD death), the corresponding HR was 3.0 (1.4, 5.4) p=.0003 and for the stroke
      alone the corresponding HR was 3.5 (1.4-8.9) p=.01. The higher cumulative
      incidence of the expanded endpoint in diabetic participants carrying the FABP2
      polymorphism versus non-diabetic carriers was consistently present throughout the
      5 years of the study (p=.0002). We conclude that based on the VA-HIT data, the
      Thr-54 polymorphism of the FABP2 gene is associated with a 2-3.5-fold increase in
      cardiovascular risk in dyslipidemic men with diabetes compared to their non
      diabetic counterparts.

PMID- 16945374
TI  - Common variants of apolipoprotein A-IV differ in their ability to inhibit low
      density lipoprotein oxidation.
AB  - Apolipoprotein A-IV (apoA-IV) inhibits lipid peroxidation, thus demonstrating
      potential anti-atherogenic properties. The aim of this study was to investigate
      how the inhibition of low density lipoprotein (LDL) oxidation was influenced by
      common apoA-IV isoforms. Recombinant wild type apoA-IV (100 microg/ml)
      significantly inhibited the oxidation of LDL (50 microg protein/ml) by 5 microM
      CuSO(4) (P<0.005), but not by 100 microM CuSO(4), suggesting that it may act by
      binding copper ions. ApoA-IV also inhibited the oxidation of LDL by the water
      soluble free-radical generator 2,2'-azobis(amidinopropane) dihydrochloride (AAPH;
      1 mM), as shown by the two-fold increase in the time for half maximal conjugated
      diene formation (T(1/2); P<0.05) suggesting it can also scavenge free radicals in
      the aqueous phase. Compared to wild type apoA-IV, apoA-IV-S347 decreased T(1/2)
      by 15% (P=0.036) and apoA-IV-H360 increased T(1/2) by 18% (P=0.046). All apoA-IV
      isoforms increased the relative electrophoretic mobility of native LDL,
      suggesting apoA-IV can bind to LDL and acts as a site-specific antioxidant. The
      reduced inhibition of LDL oxidation by apoA-IV-S347 compared to wild type apoA-IV
      may account for the previous association of the APOA4 S347 variant with increased
      CHD risk and oxidative stress.

PMID- 16945375
TI  - Nicotinic acid induces secretion of prostaglandin D2 in human macrophages: an in
      vitro model of the niacin flush.
AB  - Nicotinic acid is a safe, broad-spectrum lipid agent shown to prevent
      cardiovascular disease, yet its widespread use is limited by the prostaglandin D2
      (PGD2) mediated niacin flush. Previous research suggests that nicotinic acid
      induced PGD2 secretion is mediated by the skin, but the exact cell type remains
      unclear. We hypothesized that macrophages are a source of nicotinic acid-induced
      PGD2 secretion and performed a series of experiments to confirm this. Nicotinic
      acid (0.1-3 mM) induced PGD2 secretion in cultured human macrophages, but not
      monocytes or endothelial cells. The PGD2 secretion was dependent on the
      concentration of nicotinic acid and the time of exposure. Nicotinuric acid, but
      not nicotinamide, also induced PGD2 secretion. Pre-incubation of the cells with
      aspirin (100 microM) entirely prevented the nicotinic acid effects on PGD2
      secretion. The PGD2 secreting effects of nicotinic acid were additive to the
      effects of the calcium ionophore A23187 (6 microM), but were independent of extra
      cellular calcium. These findings, combined with recent in vivo work, provide
      evidence that macrophages play a significant role in mediating the niacin flush
      and may lead to better strategies to eliminate this limiting side effect.

PMID- 16945376
TI  - Deuterium/hydrogen ratio analysis of thymol, carvacrol, gamma-terpinene and p
      cymene in thyme, savory and oregano essential oils by gas chromatography
      pyrolysis-isotope ratio mass spectrometry.
AB  - Isotope ratio mass spectrometry online coupled with capillary gas chromatography
      (GC-Py-IRMS) on column INNOWAX is used in the origin specific analysis and the
      authenticity control of the phenolic essential oils (EOs). Isotopic data
      delta(2)H(V-SMOW) of thymol and carvacrol in natural essential oils were
      evidently more depleted than synthetic products (from -49 to 7 per thousand for
      thymol and -61 per thousand for carvacrol). delta(2)H(V-SMOW) values of p-cymene,
      gamma-terpinene and thymol in authentic thyme oils (Thymus vulgaris L. and Thymus
      zygis L.) were found from -300 to -270 per thousand, from -285 to -248 per
      thousand and from -259 to -234 per thousand, respectively. delta(2)H(V-SMOW)
      values of carvacrol and p-cymene in authentic oregano oils (Origanum
      heracleoticum L., Coridothymus capitatus L. and Origanum compactum L.) varied
      from -223 to -193 per thousand and from -284 to -259 per thousand, respectively.
      For authentic Satureja montana subsp. montana essential oils, the mean
      delta(2)H(V-SMOW) value for aromatic compounds were found to be the following:
      gamma-terpinene -273 per thousand (SD=4.6 per thousand) and p-cymene -283 per
      thousand (SD=3.0 per thousand), thymol -245 per thousand (SD=1.8 per thousand)
      and carvacrol -226 per thousand (SD=1.7 per thousand). In addition, p-cymene was
      previously found as a precursor of the biosynthesis of thymol and carvacrol in
      thyme oil, thus, we considered p-cymene as an endogenous reference compound (ERC)
      for D/H ratio analysis. The isotopic fractionation factors alpha(thymol/p
      cymene)=1.05 and alpha(carvacrol/p-cymene)=1.08 were obtained and also used to
      control the authenticity of the phenolic EOs.

PMID- 16945378
TI  - Capillary electrophoresis with laser-induced fluorescence detection for detailed
      studies on N-linked oligosaccharide profile of therapeutic recombinant monoclonal
      antibodies.
AB  - Total N-linked oligosaccharide profiling method for recombinant monoclonal
      antibody (rmAb) using capillary electrophoresis with laser-induced fluorescence
      detection (CE-LIF) and an approach for detailed structural analysis of N-linked
      oligosaccharide were developed. A CE-LIF method using 2-aminobenzoic acid (2-AA)
      as a fluorogenic reagent allowed sensitive detection of several minor peaks
      besides typical asialo-biantennary complex type oligosaccharides in the analysis
      of N-linked oligosaccharide from a commercial rmAb pharmaceutical, rituximab.
      These minor peaks were successfully assigned as sialo-biantennary complex type
      and high-mannose type oligosaccharides by comparison with the migration times of
      2-AA derivatized oligosaccharides which were separately fractionated and
      determined by high-performance liquid chromatography (HPLC) and matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). In
      development of biopharmaceuticals, it is important to evaluate these minor
      oligosaccharides, because some of these minor glycans are likely to influence
      immunogenicity and clearance rate in vivo. The repetitive analysis using CE-LIF
      showed excellent precision in relative corrected peak areas. These results
      demonstrate that the present CE-LIF method is applicable for both structural
      characterization and quantitative profiling of N-linked oligosaccharides derived
      from rmAb pharmaceuticals. The present method will be a powerful tool for rapid,
      quantitative and exhaustive evaluation of N-linked oligosaccharides in various
      stages of rmAb pharmaceutical development such as clone selection, bioprocess
      control, and routine lot release testing to ensure product efficacy and
      consistency.

PMID- 16945377
TI  - Single laboratory validation of a method for the determination of Bisphenol A,
      Bisphenol A diglycidyl ether and its derivatives in canned foods by reversed
      phase liquid chromatography.
AB  - A method was developed and validated for the simultaneous determination of
      Bisphenol A (BPA), Bisphenol A diglycidyl ether (BADGE), BADGE-H2O, BADGE-2H2O,
      BADGE-H2O-HCl, BADGE-HCl, and BADGE-2HCl in canned food using reversed phase high
      performance liquid chromatography (HPLC) with fluorescence detection;
      chromatographic separation of all seven analytes was achieved (Rs > or = 1.08)
      using HPLC gradient elution technique. Acetonitrile was used to extract the
      analytes from the food matrix before subjecting the samples to liquid-liquid
      extraction, solid-phase extraction for further clean-up and preconcentration
      prior to HPLC analysis. Excellent inter-day precision data (n = 10) and intra-day
      precision data (n = 5) were obtained on a 200 microg/kg spiked sample. The RSD
      ranged from 0.20% to 2.96% for the inter-day precision tests, and 0.04% to 2.82%
      for the intra-day precision tests. Accuracy was measured at three concentration
      levels: 200, 1000, and 2000 microg/kg; recoveries ranged from 86.07% to 114.06%.
      The excellent validation data suggests that this method can be applied on canned
      foods for the determination of migration of BPA, BADGE and its derivatives from
      can coatings into food.

PMID- 16945379
TI  - Anionic phospholipid coatings in capillary electrochromatography. Binding of Ca2+
      to phospholipid phosphate group.
AB  - Anionic phospholipids phosphatidic acid (PA), phosphatidylglycerol (PG),
      phosphatidylinositol (PI), and phosphatidylserine (PS) were examined for their
      effect on 1-palmitoyl-2-oleyl-sn-glycero-3-phosphatidylcholine (POPC)-containing
      liposomes used as coating material in capillary electrochromatography. Liposome
      solvent was N-(2-hydroxyethyl)piperazine-N'-(2-ethanesulfonic acid) (HEPES)
      buffer at pH 7.4 with and without 3 mM of CaCl2. The background electrolyte
      solution was HEPES buffer at pH 7.4. The net charge, size, and short-term
      stability of the liposomes were measured with a Zetasizer. Results showed that
      calcium interacts with all liposomes but most strongly with POPC/PA. The relative
      migration times, retention factors, and resolution of the model analytes (one
      cationic, three uncharged ions, and one anionic) were studied. All liposomes
      successfully coated the silica capillary. Without calcium the strongest
      interaction and best separation of the analytes were with the POPC/PI and POPC/PS
      coatings, while interactions with the POPC/PA coating were weak. Calcium enhanced
      the interactions of the model analytes with all coatings, and the interactions
      were then strongest with the POPC/PA coating. In the presence of calcium there
      appears to be a slight reorganization of the coating with increasing number of
      runs. Our results indicate strong interactions between calcium and the phosphate
      groups in phospholipids and demonstrate the significant role of the phospholipid
      polar head group in phospholipid coatings on silica surfaces.

PMID- 16945380
TI  - One-step purification of a recombinant protein from a whole cell extract by
      reversed-phase high-performance liquid chromatography.
AB  - We have developed a one-step facile, flexible and readily scalable purification
      method for a recombinant protein, TM 1-99 (113 amino acid residues; 12,837 Da)
      based on reversed-phase high-performance liquid chromatography (RP-HPLC) from an
      E. coli cell lysate. Following cell lysis, the cell contents were extracted with
      0.1% aqueous trifluoroacetic acid (TFA), applied directly under conditions of
      high sample load to a narrow bore RP-HPLC C(8) column (150 mm x 2.1 mm I.D.) and
      eluted by a shallow gradient of acetonitrile (0.1%/min). Loads of 23 and 48 mg of
      lyophilized crude cell extract produced 2.4 and 4.2mg of purified product (>94%
      pure), respectively, at >94% recovery. Our results show the excellent potential
      of one-step RP-HPLC for purification of recombinant proteins from cell lysates,
      where high yields of purified product and greater purity are achieved compared to
      affinity chromatography. Such an approach was also successful in purifying just
      trace levels (<0.1% of total contents of crude sample) of TM 1-99 from a cell
      lysate.

PMID- 16945381
TI  - Analysis of estrogens in environmental waters using polymer monolith in-polyether
      ether ketone tube solid-phase microextraction combined with high-performance
      liquid chromatography.
AB  - A simple, rapid and sensitive on-line method for simultaneous determination of
      four endocrine disruptors (17beta-estradiol, estriol, bisphenol A and 17alpha
      ethinylestradiol) in environmental waters was developed by coupling in-tube solid
      phase microextraction (SPME) to high-performance liquid chromatography (HPLC)
      with fluorescence detection (FLD). A poly(acrylamide-vinylpyridine-N,N'-methylene
      bisacrylamide) monolith, synthesized inside a polyether ether ketone (PEEK) tube,
      was selected as the extraction medium. To achieve optimum extraction performance,
      several parameters were investigated, including extraction flow-rate, extraction
      time, and pH value, inorganic salt and organic solvent content of the sample
      matrix. By simply filtered with nylon membrane filter and adjusting the pH of
      samples to 6.0 with phosphoric acid, the sample solution then could be directly
      injected into the device for extraction. Low detection limits (S/N=3) and
      quantification limits (S/N=10) of the proposed method were achieved in the range
      of 0.006-0.10 ng/mL and 0.02-0.35 ng/mL from spiked lake waters, respectively.
      The calibration curves of four endocrine disruptors showed good linearity ranging
      from quantification limits to 50 ng/mL with a linear coefficient R(2) value above
      0.9913. Good method reproducibility was also found by intra- and inter-day
      precisions, yielding the RSDs less than 12 and 9.8%, respectively. Finally, the
      proposed method was successfully applied to the determination of these compounds
      in several environmental waters.

PMID- 16945382
TI  - Rapid determination of histamine and its metabolites in mice hair by ultra
      performance liquid chromatography with time-of-flight mass spectrometry.
AB  - The rapid determination of histamine (HA) and several metabolites, i.e., 1
      methylhistamine (MHA), imidazole-4-acetic acid (IAA), and 1-methyl-4-imidazole
      acetic acid (MIAA), in mice hairs was performed by ultra-performance liquid
      chromatography with time-of-flight mass spectrometry (UPLC-TOF-MS). HA and MHA,
      having a primary amino group (NH(2)) in their structures, were first labeled with
      4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole (DBD-F) at 60 degrees
      C for 45 min in the mixture of 0.1M borax (pH 9.3) and acetonitrile (CH(3)CN). On
      the other hand, 4-(N,N-dimethylaminosulfonyl)-7-piperazino-2,1,3-benzoxadiazole
      (DBD-PZ) was used for the labeling of a carboxylic acid group (COOH) in IAA and
      MIAA in the presence of 2,2'-dipyridyl disulfide (DPDS) and triphenylphosphine
      (TPP). The reaction with DBD-PZ was completed at 50 degrees C after 2h. The
      resulting derivatives of HA and the metabolites were perfectly separated using an
      ACQUITY UPLCtrade mark BEH C(18) column (1.7 microm, 100 x 2.1mm, i.d.) with the
      mixture of 20 mM HCOONH(4) and CH(3)CN (8:2). The structures of HA and the
      metabolites were identified from the protonated-molecular ions [M+H](+) and the
      de-protonated-molecular ions [M-H](-) of authentic compounds, obtained from TOF
      MS measurement. A good linearity was achieved from the calibration curves,
      obtained by plotting the peak area ratios of the analytes relative to the
      internal standard (IS), i.e., histamine-alpha,alpha,beta,beta-d(4) (HA-d(4)) or 4
      imidazolecarboxylic acid (ICA), against the injected amounts of each compound
      (1.0-25 pmol, r(2)=0.998). The detection limits of HA and the metabolites were
      less than 1 pmol. The proposed method was applied to the determination in the
      hair shafts of C3H mice. The average concentrations of HA, MHA, IAA and MIAA in
      1mg of the hair shafts were 16.3 pmol (n=7), 21.6 pmol (n=3), 6.6 pmol (n=3) and
      7.1 pmol (n=3), respectively. Because the proposed method provides good mass
      accuracy and the trace detection of HA and several metabolites in hair, this
      analytical technique seems to be applicable for the determination of various
      biological compounds in hair.

PMID- 16945383
TI  - Determination of fragrance allergens in cosmetics by size-exclusion
      chromatography followed by gas chromatography-mass spectrometry.
AB  - A method using size-exclusion chromatography (SEC) combined with gas
      chromatography-mass spectrometry (GC-MS) was developed for the quantitation of 24
      restricted allergenic fragrance compounds in cosmetic samples. To achieve
      reproducible results fragrance calibration has to be performed with propyl
      acetate as a solvent containing a constant proportion of matrix components. With
      the exception of hydroxycitronellal (66+/-5%) all compounds showed good recovery
      rates in the range of 90-120%. The mean accuracy (relative error) was 1+/-10% for
      all 24 compounds in five spiked creams (10 mg/kg per allergen) and 8+/-34% in a
      reference sample (4-15 mg/kg). The biggest benefit compared to other methods is
      the flexible clean up with SEC which allows the determination of a large range of
      compounds in difficult matrices with GC-MS.

PMID- 16945384
TI  - Structural and redox properties of mitochondrial cytochrome c co-sorbed with
      phosphate on hematite (alpha-Fe2O3) surfaces.
AB  - The interaction of metalloproteins with oxides has implications not only for
      bioanalytical systems and biosensors but also in the areas of biomimetic
      photovoltaic devices, bioremediation, and bacterial metal reduction. Here, we
      investigate mitochondrial ferricytochrome c (Cyt c) co-sorption with 0.01 and 0.1
      M phosphate on hematite (alpha-Fe2O3) surfaces as a function of pH (2-11).
      Although Cyt c sorption to hematite in the presence of phosphate is consistent
      with electrostatic attraction, other forces act upon Cyt c as well. The
      occurrence of multilayer adsorption, and our AFM observations, suggest that Cyt c
      aggregates as the pH approaches the Cyt c isoelectric point. In solution,
      methionine coordination of heme Fe occurs only between pH 3 and 7, but in the
      presence of phosphate this coordination is retained up to pH 10. Electrochemical
      evidence for the presence of native Cyt c occurs down to pH 3 and up to pH 10 in
      the absence of phosphate, and this range is extended to pH 2 and 11 in the
      presence of phosphate. Cyt c that initially adsorbs to a hematite surface may
      undergo conformation change and coat the surface with unfolded protein such that
      subsequently adsorbing protein is more likely to retain the native conformational
      state. AFM provides evidence for rapid sorption kinetics for Cyt c co-sorbed with
      0.01 or 0.1 M phosphate. Cyt c co-sorbed with 0.01 M phosphate appears to unfold
      on the surface of hematite while Cyt c co-sorbed with 0.1 M phosphate possibly
      retains native conformation due to aggregation.

PMID- 16945385
TI  - A flow cytometry procedure for simultaneous characterization of cell DNA content
      and expression of intracellular protein kinase C-zeta.
AB  - A selective involvement of protein kinase C-zeta (PKC-zeta) in the events
      regulating cell proliferation has been recently proposed. Here we report a flow
      cytometric method allowing the simultaneous association of intracellular PKC-zeta
      expression or phosphorylation with each cell cycle phase. Current methods for
      flow cytometry analysis were applied to several cell lines and compared to the
      method developed in our laboratory. The latter includes 2% paraformaldehyde
      (PFA), as fixing agent, a permeabilization/saturation step by means of a solution
      containing 150 mM NaCl, 5 mM EDTA, 50 mM Tris-HCl pH 7.4, 0.05% NP-40, 0.25%
      lambda-carrageenan and 0.02% NaN3, followed by labelling with a primary antibody
      (PKC-zeta or P-PKC-zeta) and with the appropriate FITC-conjugated secondary
      antibody. Cells processed by such a method disclosed no substantial modification
      of light scattering features with respect to live cells. In addition,
      stainability with anti-PKC-zeta or anti-P-PKC-zeta antibodies was well preserved
      while stoichiometric staining of DNA with PI enabled accurate cell cycle
      analysis. Results show that a distinct up-regulation of P-PKC-zeta in G2/M phase
      occurs. The method here described, therefore, represents a simple, reproducible
      and conservative assay for a simultaneous assessment of intracellular PKC or P
      PKC modulations within each cell cycle phase.

PMID- 16945386
TI  - The acute treatment of nerve agent exposure.
AB  - Nerve agents (NA) are simple and cheap to produce but can produce casualties on a
      massive scale. They have already been employed by terrorist organizations and
      rogue states on civilians and armed forces alike. By inhibiting the enzyme
      acetylcholine esterase, NAs prevent the breakdown of the neurotransmitter
      acetylcholine. This results in over-stimulation of muscarinic and nicotinic
      receptors in the autonomic and central nervous systems and at the neuromuscular
      junction. Increased parasympathetic stimulation produces miosis, sialorrhea,
      bronchospasm and bronchorrhea. Effects at the neuromuscular junction cause
      weakness, fasciculations, and eventually paralysis. Central effects include
      altered behavior and mental status, loss of consciousness, seizures, or apnea.
      Most deaths are due to respiratory failure. Treatment with atropine competitively
      blocks the parasympathetic effects. Oximes like pralidoxime salvage acetylcholine
      esterase by "prying off" NA, provided the attachment has not "aged" to an
      irreversible bond. This reverses weakness. Benzodiazepines like diazepam are
      effective against NA induced seizures. Mortality has been surprisingly low. If
      victims can survive the first 15 to 20 min of a vapor attack, they will likely
      live. The low mortality rate to date underscores that attacks are survivable and
      research reveals even simple barriers such as clothing offer substantial
      protection. This article reviews the properties of NAs and how to recognize the
      clinical features of NA intoxication, employ the needed drugs properly, and
      screen out anxious patients who mistakenly believe they have been exposed.

PMID- 16945387
TI  - PNN-curve: a new 2D graphical representation of DNA sequences and its
      application.
AB  - We introduce a novel 2D graphical representation of DNA sequences based on the
      pairs of the neighboring nucleotides (PNNs). Then we get the PNNs' distributions
      and obtain a y-M. The construction of the PNN-curve has some important advantages
      (1) It avoids loss of information and the PNN-curve standing for DNA sequences
      does not overlap or intersect with itself. (2) The novel 2D representation is
      more sensitive. The utility of this method can be illustrated by the examination
      of similarities/dissimilarities among the coding sequences of the first exon of
      beta-globin gene of eleven different species in Table 2.

PMID- 16945388
TI  - A simplified model for mitochondrial ATP production.
AB  - Most of the adenosine triphosphate (ATP) synthesized during glucose metabolism is
      produced in the mitochondria through oxidative phosphorylation. This is a complex
      reaction powered by the proton gradient across the mitochondrial inner membrane,
      which is generated by mitochondrial respiration. A detailed model of this
      reaction, which includes dynamic equations for the key mitochondrial variables,
      was developed earlier by Magnus and Keizer. However, this model is
      extraordinarily complicated. We develop a simpler model that captures the
      behavior of the original model but is easier to use and to understand. We then
      use it to investigate the mitochondrial responses to glycolytic and calcium
      input. We use the model to explain experimental observations of the opposite
      effects of raising cytosolic Ca(2+)in low and high glucose, and to predict the
      effects of a mutation in the mitochondrial enzyme nicotinamide nucleotide
      transhydrogenase (Nnt) in pancreatic beta-cells.

PMID- 16945389
TI  - Adaptation of proteins to different environments: a comparison of proteome
      structural properties in Bacillus subtilis and Escherichia coli.
AB  - We compared amino acid solvent accessibilities and helix propensities in data
      sets of Escherichia coli and Bacillus subtilis proteins. These species reside in
      very different environments and hold very different physiological properties.
      From the observations, it was proposed that the cytoplasm of B. subtilis is more
      ion-rich compared to the cytoplasm of E. coli, which might be more hydrophobic;
      therefore, during evolution these differences have resulted in different protein
      folding tracks. Such inherent differences imply that the results of bioinformatic
      analyses of protein structures might depend on the species from which the
      proteins are picked. It is also suggested that different cytoplasmic environments
      cause E. coli and B. subtilis to be appropriate for expression of distinct types
      of proteins.

PMID- 16945390
TI  - Role of epigallocatechin gallate (EGCG) in the treatment of breast and prostate
      cancer.
AB  - Green tea and its major constituent epigallocatechin gallate (EGCG) have been
      extensively studied as a potential treatment for a variety of diseases, including
      cancer. Epidemiological data have suggested that EGCG may provide protective
      effects against hormone related cancers, namely breast or prostate cancer.
      Extensive in vitro investigations using both hormone responsive and non
      responsive cell lines have shown that EGCG induces apoptosis and alters the
      expression of cell cycle regulatory proteins that are critical for cell survival
      and apoptosis. This review will highlight the important in vitro mechanistic
      actions elicited by EGCG in various breast and prostate cancer cell lines.
      Additionally, the actions of green tea/EGCG in in vivo models for these cancers
      as well as in clinical trials will be discussed.

PMID- 16945391
TI  - Reactive oxygen species damaged human serum albumin in patients with type 1
      diabetes mellitus: biochemical and immunological studies.
AB  - The role of hydroxyl radical (.OH) damaged human serum albumin (HSA) in type 1
      diabetes has been investigated in the present study. Hydroxyl radical induced
      modification on HSA has been studied by UV absorption spectroscopy, ANS
      fluorescence and carbonyl estimation. Hydroxyl radical modified HSA was found to
      be highly immunogenic in rabbits as compared to native HSA. The binding
      characteristics of circulating autoantibodies in type 1 diabetes patients against
      native and modified HSA were assessed. Diabetes patients (n=31) were examined by
      direct binding ELISA and the results were compared with healthy age-matched
      controls (n=22). High degree of specific binding by 54.8% of patients sera
      towards .OH modified HSA, in comparison to its native analogue (p<0.05) was
      observed. Sera from those type 1 diabetes patients having smoking history, high
      aging with high degree of disease showed substantially stronger binding to .OH
      modified HSA over native HSA in particular. Normal human sera showed negligible
      binding with either antigen. Competitive inhibition ELISA reiterates the direct
      binding results. Gel retardation assay further substantiated the enhanced
      recognition of modified HSA by circulating autoantibodies in diabetes patients.
      The increase in total serum protein carbonyl levels in the diabetes patients was
      largely due to an increase in oxidized albumin. HSA of diabetes mellitus patients
      (DM-HSA) and normal subjects (normal-HSA) were purified on a Sephacryl S-200 HR
      column. Spectroscopic analysis confirmed that the DM-HSA samples contained higher
      levels of carbonyls than normal-HSA (p<0.001). DM-HSA was conformationally
      altered, with more exposure of its hydrophobic regions. Collectively, the
      oxidation of plasma proteins, especially HSA, might enhance oxidative stress in
      type 1 diabetes mellitus patients.

PMID- 16945392
TI  - Anti-diabetic effects of electrolyzed reduced water in streptozotocin-induced and
      genetic diabetic mice.
AB  - Oxidative stress is produced under diabetic conditions and is likely involved in
      progression of pancreatic beta-cell dysfunction found in diabetes. Both an
      increase in reactive oxygen free radical species (ROS) and a decrease in the
      antioxidant defense mechanism lead to the increase in oxidative stress in
      diabetes. Electrolyzed reduced water (ERW) with ROS scavenging ability may have a
      potential effect on diabetic animals, a model for high oxidative stress.
      Therefore, the present study examined the possible anti-diabetic effect of ERW in
      two different diabetic animal models. The genetically diabetic mouse strain
      C57BL/6J-db/db (db/db) and streptozotocin (STZ)-induced diabetic mouse were used
      as insulin deficient type 1 and insulin resistant type 2 animal model,
      respectively. ERW, provided as a drinking water, significantly reduced the blood
      glucose concentration and improved glucose tolerance in both animal models.
      However, ERW fail to affect blood insulin levels in STZ-diabetic mice whereas
      blood insulin level was markedly increased in genetically diabetic db/db mice.
      This improved blood glucose control could result from enhanced insulin
      sensitivity, as well as increased insulin release. The present data suggest that
      ERW may function as an orally effective anti-diabetic agent and merit further
      studies on its precise mechanism.

PMID- 16945393
TI  - Ginseng: Cardiotonic in adult rat cardiomyocytes, cardiotoxic in neonatal rat
      cardiomyocytes.
AB  - Ginsengs are widely used to improve cardiac health and circulation. Loosely
      termed as ginsengs, Asian (Panax), Siberian and Ashwagandha (Indian Ginseng)
      Indian ginsengs are prepared from different plants. We tested the popular belief
      of cardiotonic effects of ginsengs using both neonatal and adult rat
      cardiomyocytes, comparing extracts from the three ginsengs. Addition of 10% v/v
      of extract (100 microl of extract/ml of culture medium) of each of the ginsengs
      resulted in a rapid (<10 s) cessation of beating in neonatal cardiomyocytes due
      to calcium overload, while sequential dilutions revealed that treatment with a
      low dose (0.01% v/v, 0.1 microl/ml of the medium) resulted in constant, regular
      beats (transients), and a slight elevation of diastolic calcium without overload.
      Addition of extracts to sparking, calcium-tolerant adult cardiomyocytes resulted
      in initiation of calcium transients, and adult cells were able to tolerate
      exposure to high concentrations of extract. Cardiotonic effects in adult cells
      (cardiotoxicity in neonatal cells) were most profound with Asian ginseng (2.6
      times that of Siberian ginseng, 1.6 times that of Indian ginseng) probably due to
      the active ingredients (ginsenosides in Asian, eleutherosides in Siberian and
      withanolides in Indian) being structurally different. We conclude that fully
      developed cardiomyocytes are able to accommodate higher doses of ginseng than
      neonatal cells, and that the effects of ginseng on newly formed, developing
      myocytes, could be extremely deleterious to the fetus. However, for adults,
      ginseng might well be a 'tonic' in its ability to increase beating and
      intramyocytic calcium levels.

PMID- 16945394
TI  - Impaired self-initiated task preparation during task switching in Parkinson's
      disease.
AB  - Patients with Parkinson's disease (PD) typically show reduced performance in
      clinical tests involving cognitive control processes, presumably due to reduced
      availability of dopamine in striatofrontal neuronal circuits. Although task
      switching paradigms are considered as an ideal experimental measure of cognitive
      control, previous studies on task switching in PD have yielded ambiguous results,
      indicating that performance deficits depend on the specific task requirements.
      Among these, the aspect of self-initiated as opposed to externally triggered task
      preparation seems to play an important role, as evidenced by recent research. To
      address this topic, the present study investigated PD patients and age-matched
      controls (n=16) with a sequential switching task in which the upcoming task was
      predicted by two different types of cues. Firstly, every task was predicted by an
      external visual cue of varying utility (long versus short precuing interval).
      Additionally, the tasks were predictable on the basis of a fixed task sequence
      (AABB), which placed relatively higher demands on self-initiated task
      preparation. After considerable practice, the sequence was changed to random.
      Increased reaction times following sequence removal indicated prior use of the
      sequence in both groups. However, in contrast to healthy age-matched controls, PD
      patients did not learn to use the predictable task sequence to a greater extent
      when the utility of the visual task cue was low due to a short precuing interval.
      This finding is interpreted as evidence for a specific impairment in self
      initiated as opposed to externally triggered task preparation.

PMID- 16945395
TI  - Rightward bisection errors for letter lines: the role of semantic information.
AB  - When bisecting words in their middle, people reveal leftward bisection errors.
      This tendency might emerge from an attentional bias towards the beginning of the
      word. However, when longer meaningless letter strings are presented, people
      reveal a rightward bisection bias. To test the role of semantic information on
      leftward or rightward bisection biases, we tested letter line bisection
      performance in healthy right-handed students in four independent experiments. A
      third of the letter lines contained an embedded four-letter word to the left of
      true centre, another third contained an embedded four-letter word to the right of
      true centre, while the remaining lines contained no words. Half of these words
      were emotional words, the other half were neutral words. Results across
      experiments revealed a stronger rightward bisection bias: (i) for letter lines
      containing emotional as compared to neutral words, (ii) for letter lines
      containing words in the left as compared to right half of the lines, and (iii)
      for those experiments in which the spatial position of letter lines remained
      within a narrow body-centred space. Findings from this study suggest that letter
      line bisection performance might be only minimally determined by visuo-spatial
      attention. Rather, letter line perception might activate the left hemisphere more
      than the right hemisphere, shifting the subjective midpoint to the right of true
      centre. Leftward bisection biases for words only, as had been described in the
      literature, may thus have resulted from automated reading strategies rather than
      from attentional biases towards the left hemispace.

PMID- 16945396
TI  - Exercise effects stress-induced analgesia and spatial learning in rats.
AB  - Previous studies indicated that intensity level may be a determining factor in
      the beneficial or detrimental effects of exercise on spatial memory, as chronic
      low-intensity level exercise appears to enhance learning and memory which
      stressful situations may impair. This study examines the effects of different
      intensity levels of acute exercise (treadmill running) on spatial memory in rats.
      Using the Morris water maze, spatial learning was measured in animals exposed to
      treadmill running at low- (20-22 m/min for 25 min daily) and high-intensity (25
      m/min for 25 min daily) levels of exercise. A stress control using an electric
      foot shock was used to examine if the high-intensity exercise was sufficient to
      serve as a stressor. Stress level was estimated by examining tail flick latencies
      as a measure of stress-induced analgesia. The results indicate that high
      intensity exercise at a level that may not induce an analgesic state is
      sufficient to impair early acquisition of spatial learning. However, with
      additional trials, all animals are capable of learning the task. Acute exposure
      to the electric foot shock impaired learning in the Morris water maze.
      Surprisingly, across all studies, there was a significantly higher analgesic
      state post-swim as compared to pre-swim. The results indicate that irrespective
      of stress level prior to water maze testing, swimming in the Morris water maze
      repeatedly for short durations of time is enough to induce an analgesic state.

PMID- 16945397
TI  - Study of a peak in cavitation activity from HIFU exposures using TA fluorescence.
AB  - Methods of measuring the sound field and focal region of a 1.05 MHz high
      intensity focused ultrasound (HIFU) are described in this paper. 1.05 MHz pulsed
      HIFU with intensity 2400 W/cm(2) with a 1:1 duty cycle ("on" phase equaled "off"
      phase) was used to irradiate terephthalic acid (TA). Pulse periods of 0.5 ms, 1
      ms, 3.3 ms, 10 ms, 15 ms, 33 ms, 0.1s and 1s were used. The irradiation time was
      2 min. To indicate the intensity of inertial cavitation activity, the
      fluorescence intensity of hydroxyterephthalic acid (HTA) was measured. The result
      shows that the cavitation activity of pulsed HIFU peaks at a pulse period of 10
      ms, cavitation activity is significantly greater for pulse periods from 2 to 20
      ms than for others.

PMID- 16945399
TI  - Development and characterization of a Rift Valley fever virus cell-cell fusion
      assay using alphavirus replicon vectors.
AB  - Rift Valley fever virus (RVFV), a member of the Phlebovirus genus in the
      Bunyaviridae family, is transmitted by mosquitoes and infects both humans and
      domestic animals, particularly cattle and sheep. Since primary RVFV strains must
      be handled in BSL-3+ or BSL-4 facilities, a RVFV cell-cell fusion assay will
      facilitate the investigation of RVFV glycoprotein function under BSL-2
      conditions. As for other members of the Bunyaviridae family, RVFV glycoproteins
      are targeted to the Golgi, where the virus buds, and are not efficiently
      delivered to the cell surface. However, overexpression of RVFV glycoproteins
      using an alphavirus replicon vector resulted in the expression of the
      glycoproteins on the surface of multiple cell types. Brief treatment of RVFV
      glycoprotein expressing cells with mildly acidic media (pH 6.2 and below)
      resulted in rapid and efficient syncytia formation, which we quantified by beta
      galactosidase alpha-complementation. Fusion was observed with several cell types,
      suggesting that the receptor(s) for RVFV is widely expressed or that this acid
      dependent virus does not require a specific receptor to mediate cell-cell fusion.
      Fusion occurred over a broad temperature range, as expected for a virus with both
      mosquito and mammalian hosts. In contrast to cell fusion mediated by the VSV-G
      glycoprotein, RVFV glycoprotein-dependent cell fusion could be prevented by
      treating target cells with trypsin, indicating that one or more proteins (or
      protein-associated carbohydrate) on the host cell surface are needed to support
      membrane fusion. The cell-cell fusion assay reported here will make it possible
      to study the membrane fusion activity of RVFV glycoproteins in a high-throughput
      format and to screen small molecule inhibitors for the ability to block virus
      specific membrane fusion.

PMID- 16945398
TI  - Cervical keratinocytes containing stably replicating extrachromosomal HPV-16 are
      refractory to transformation by oncogenic H-Ras.
AB  - Ras expression in human epithelial cells with integrated HPV genomes has been
      shown to cause tumorigenic transformation. The effects of Ras in cells
      representing early stage HPV-associated disease (i.e., when HPV is
      extrachromosomal and the oncogenes are under control of native promoters) have
      not been examined. Here, we used human cervical keratinocyte cell lines
      containing stably replicating extrachromosomal HPV-16 and present the novel
      finding that these cells resist transformation by oncogenic H-Ras. Ras expression
      consistently diminished anchorage-independent growth (AI), reduced E6 and E7
      expression, and caused p53 induction in these cells. Conversely, AI was enhanced
      or maintained in Ras-transduced cervical cells that were immortalized with a
      16E6/E7 retrovirus, and minimal effects on E6 and E7 expression were observed.
      Ras expression with either episomal HPV-16 or LXSN-E6/E7 was insufficient for
      tumorigenic growth suggesting that other events are needed for tumorigenic
      transformation. In conclusion, our results indicate that Ras-mediated
      transformation depends on the context of HPV oncogene expression and that this is
      an important point to address when developing HPV tumor models.

PMID- 16945401
TI  - Flow patterns of dairy wastewater constructed wetlands in a cold climate.
AB  - Conservative tracer experiments, and spatial temperature and dissolved oxygen
      mapping within four subsurface treatment wetlands employed in this study
      demonstrated the importance of supplemental aeration and vegetation in reducing
      preferential flows in cold climate treatment wetlands. Four constructed wetlands,
      employing horizontal subsurface flow were used to treat dairy wastewater in a 2 x
      2 factorial design consisting of two wetland cells with vegetation and two with
      supplemental aeration. Four tracer studies were conducted between November 2004
      and May 2005. Two key observations were made, demonstrating that vegetation and
      aeration can be utilized in cold regions to prevent clogging and freezing,
      thereby reducing preferential flow paths which can reduce treatment efficiencies:
      (1) vegetation contributed to thermal protection and (2) aeration increased
      temperature and mixing. A comparison of multiple wetland cells with varying flow
      rates showed that the use of pore volume in tracer response curves was a better
      indicator of preferential flows than other indicators including volumetric
      efficiency, hydraulic efficiency and number of continuosly stirred tank reactors
      (CSTRs). This research helps further establish how constructed wetlands are a
      viable tool for treating wastewater in cold climates.

PMID- 16945400
TI  - A fused gene of nucleoprotein (NP) and herpes simplex virus genes (VP22) induces
      highly protective immunity against different subtypes of influenza virus.
AB  - We evaluated the immunogenicity and protective activity of plasmid DNA vaccines
      encoding the influenza virus NP gene (pNP) alone or in combination with the
      herpes simplex virus type 1 protein 22 gene (pVP22). Optimal immune responses
      were observed in BALB/c mice immunized with the combination of pVP22 plus pNP, as
      assessed by enzyme-linked immunosorbent assay (ELISA), enzyme-linked immunospot
      (ELISPOT) and intracellular cytokine staining (ICCS). These mice also showed
      maximal resistance following challenge with the A/PR/8/34 (H1N1) and A/Udron/72
      (H3N2) strains of influenza virus. The susceptibility of immunized mice to virus
      infection was significantly increased following depletion of either CD4+ or CD8+
      T cells. These results indicate that a plasmid DNA vaccine encoding pVP22 plus NP
      induces a high level of cross-protective immunity against influenza virus
      subtypes.

PMID- 16945402
TI  - Degradation of plasmid and plant DNA in water microcosms monitored by natural
      transformation and real-time polymerase chain reaction (PCR).
AB  - Extracellular DNA exists in the environment and can be taken up by competent
      bacterial cells, leading to horizontal gene transfer. The persistence of
      extracellular plasmid and plant DNA in water microcosms was monitored in this
      study. Water samples were two groundwater (GW1 and GW2) and one river water (RW)
      samples. Three treatments included: (1) intact, (2) 0.22 microm filter
      sterilized, and (3) autoclaved water. DNA from a plasmid (pNS1) and a transgenic
      Bt (Bacillus thuringiensis) corn line, both carrying a neomycin
      phosphotransferase gene (nptII gene) conferring kanamycin and neomycin
      resistance, was inoculated into the microcosms at 0.4 and 0.8 microg/ml,
      respectively. By monitoring its ability to transform a competent Pseudomonas
      stutzeri strain harboring plasmid pMR7 (P. stutzeri pMR7), plasmid DNA was
      degraded to undetectable levels in the intact and/or filter-sterilized water
      treatments within 48-96 h in GW1, GW2, and RW. Meanwhile, plasmid DNA persisted
      in the autoclaved treatment throughout the entire incubation period. For plant
      DNA, a highly sensitive real-time PCR method using SYBR Green I was developed to
      monitor the degradation dynamics of the nptII gene carried by the transgenic corn
      line in the microcosms. The results showed that the concentration of plant DNA
      was reduced by two orders of magnitude (from 0.8-0.008 microg/ml) within 96 h in
      the intact and filter-sterilized treatments of GW1, GW2, and RW, in contrast to
      its persistence in the autoclaved treatment. In addition, no kanamycin resistant
      (Km R) transformants were detected from in situ transformation of P. stutzeri
      pMR7 with plasmid pNS1 DNA.

PMID- 16945404
TI  - LINK-AGE: coordination and consolidation of European biogerontology: en route
      towards formation of a European college of biogerontology.

PMID- 16945403
TI  - Synthesis of pyrrolo[2,3-d]pyrimidine nucleoside derivatives as potential anti
      HCV agents.
AB  - Several Toyocamycin (4) analogues were examined for their ability to inhibit HCV
      RNA in a replicon assay. Among the compounds examined 4-methylthio (18) and 5
      carboxamide oxime derivatives (23 and 27) of Toyocamycin were found to have good
      activity and selectivity.

PMID- 16945405
TI  - Effects on growth, photosynthesis and pigments of the freshwater moss Fontinalis
      antipyretica Hedw. after exposure to wood ash solution.
AB  - The application of wood ash from biofuel sources to the forest has been suggested
      as a source of nutrients for trees and for restoration of acidified soils and
      surface waters. Studies on the effects of wood ash on aquatic organisms and
      ecosystems are, however, few. This study investigated the effects of wood ash
      (0.1-10 g l(-1)) on the freshwater moss Fontinalis antipyretica Hedw., which has
      previously been shown to be a sensitive test organism for assessing environmental
      pollution. After nine weeks of treatment with wood ash, a significant effect of
      enhanced stem growth was observed at higher concentrations (1-10 g l(-1)). The
      concentration of wood ash was also correlated with the growth of secondary
      branches. Photosynthesis (oxygen evolution after 4 h of exposure to wood ash) was
      significantly lower in the alkaline treatments (no pH adjustment) compared to the
      treatments with neutral wood ash solutions (pH adjusted to 7.5). Furthermore,
      photosynthesis in the alkaline wood ash treatments was significantly lower
      compared to the control. The ratio between the optical density value before and
      after acidification (OD(665/665a)) was higher for all wood ash concentrations
      compared to the control. The OD(665/665a) values ranged from 1.52 to 1.61 and
      there was a difference, however not significant, between the alkaline and the
      neutral treatment at 10 g l(-1) wood ash. This study clearly demonstrated that
      wood ash may be beneficial for F. antipyretica at moderate concentrations (0.5-5
      g l(-1)), particularly when a sudden increase in pH is avoided.

PMID- 16945406
TI  - Neuro(active)steroids actions at the neuromodulatory sigma1 (sigma1) receptor:
      biochemical and physiological evidences, consequences in neuroprotection.
AB  - Steroids from peripheral sources or synthesized in the brain, i.e. neurosteroids,
      exert rapid modulations of neurotransmitter responses through specific
      interactions with membrane receptors, mainly the gamma-aminobutyric acid type A
      (GABA(A)) receptor and N-methyl-d-aspartate (NMDA) type of glutamate receptor.
      Progesterone and 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone) act as
      inhibitory steroids while pregnenolone sulfate or dehydroepiandrosterone sulfate
      act as excitatory steroids. Some steroids also interact with an atypical protein,
      the sigma(1) (sigma(1)) receptor. This receptor has been cloned in several
      species and is centrally expressed in neurons and oligodendrocytes. Activation of
      the sigma(1) receptor modulates cellular Ca(2+) mobilization, particularly from
      endoplasmic reticulum pools, and contributes to the formation of lipid droplets,
      translocating towards the plasma membrane and contributing to the recomposition
      of lipid microdomains. The present review details the evidences showing that the
      sigma(1) receptor is a target for neurosteroids in physiological conditions.
      Analysis of the sigma(1) protein sequence confirmed homologies with the
      ERG2/emopamil binding protein family but also with the steroidogenic enzymes
      isopentenyl diphosphate isomerase and 17beta-estradiol dehydrogenase. Biochemical
      and physiological arguments for an interaction of neuro(active)steroids with the
      sigma(1) receptor are analyzed and the impact on physiopathological outcomes in
      neuroprotection is illustrated.

PMID- 16945407
TI  - Fabrication methods of an engineered microenvironment for analysis of cell
      biomaterial interactions.
AB  - Success in tissue engineering requires an understanding of how cells integrate
      the signals presented from the microenvironment created by biomaterial scaffolds
      to alter their responses. Besides the presence of chemical stimuli, there is
      growing evidence that the spatial organization of cells and tissue within a 3
      dimensional (3-D) extracellular matrix (ECM) context is a critical element in
      controlling cellular function. Therefore, in order to direct cells toward a
      desirable tissue structure, it is necessary to engineer biomaterials to have
      spatiotemporal control of the presentation of regulatory signals. Given that,
      micro-patterning techniques have profited by combining micro-fabrication
      technology with the chemical conjugation of biologically active molecules to
      provide new culture systems where cells can be cultured within a specific
      geometry. The micro-engineered environments have been developed as 2- and 3-D
      structures, which have proven greatly useful as versatile platforms to study
      cell, biomaterial, and ECM interactions on both macroscopic and microscopic
      levels. The main focus of this review is a brief summary of the use of micro
      engineered substrates in the analysis of cell-biomaterial interactions with the
      aim to provide an introductory overview of practical applications available in
      the literature. In particular, topics regarding (1) the soft-lithography
      technique to prepare micro-patterned substrates for the spatial control of cell
      adhesion, (2) biomaterials stiffness-dependent cellular responses, and (3) the
      microarray techniques for analysis of cell/biomaterials interactions are
      discussed.

PMID- 16945408
TI  - Platinum nanowire nanoelectrode array for the fabrication of biosensors.
AB  - Platinum nanowire arrays can be grown by electrodeposition in polycarbonate
      membrane, with the average diameter of the nanowires about 250 nm and the height
      about 2 microm. The nanowire array prepared by the proposed method can be
      considered as nanoelectrode array (NEA) with nanoelectrode density of 5 x
      10(8)cm(-2). While the NEA can improve the signal-to-noise ratio and decrease the
      detection limit, the high surface area of the platinum NEA circumvents the
      problem of conventional platinum electrodes associated with the limited
      electroactive site. The platinum NEA can direct response to hydrogen peroxide at
      low potential of 0 V with wide linear range (1 x 10(-7)-6 x 10(-2)M) and
      sensitivity 50 times larger than that of the conventional platinum electrode.
      With the absorption of glucose oxidase onto the ordered NEA surface, the
      spatially patterned glucose oxidase improves greatly the resulting biosensor. The
      biosensor can achieve interference free determination of glucose with wide linear
      range (10(-6)-3 x 10(-2)M). The sensitivity of the glucose biosensor is one-fifth
      of the sensitivity toward hydrogen peroxide, indicating high efficiency of signal
      transduction. The biosensor was used to determine glucose in real blood samples,
      and the glucose contents determined by the present biosensor were in agreement
      with the results of existing method.

PMID- 16945409
TI  - Pore throat size and connectivity determine bone and tissue ingrowth into porous
      implants: three-dimensional micro-CT based structural analyses of porous
      bioactive titanium implants.
AB  - A porous structure comprises pores and pore throats with a complex three
      dimensional (3D) network structure, and many investigators have described the
      relationship between average pore size and the amount of bone ingrowth. However,
      the influence of network structure or pore throats for tissue ingrowth has rarely
      been discussed. Four types of bioactive porous titanium implants with different
      pore sizes and porosities (6mm in diameter and 15 mm long) were analyzed using
      specific algorithms for 3D analysis of interconnectivity based on a micro focus X
      ray computed tomography system. In vivo histomorphometric analysis was performed
      using the very same implants implanted into the femoral condyles of male rabbits
      for 6 and 12 weeks. This matching study revealed that more poorly differentiated
      pores tended to have narrow pore throats, especially in their shorter routes to
      the outside. In addition, for assessment of the entire implant, we proposed new
      two indices that represent the degree of bone and tissue ingrowth into an implant
      by considering the effect of narrow pore throats. Data obtained suggest that this
      sort of novel analysis is useful for evaluating bone and tissue ingrowth into
      porous biomaterials.

PMID- 16945410
TI  - Novel hydroxyapatite/chitosan bilayered scaffold for osteochondral tissue
      engineering applications: Scaffold design and its performance when seeded with
      goat bone marrow stromal cells.
AB  - Recent studies suggest that bone marrow stromal cells are a potential source of
      osteoblasts and chondrocytes and can be used to regenerate damaged tissues using
      a tissue-engineering (TE) approach. However, these strategies require the use of
      an appropriate scaffold architecture that can support the formation de novo of
      either bone and cartilage tissue, or both, as in the case of osteochondral
      defects. The later has been attracting a great deal of attention since it is
      considered a difficult goal to achieve. This work consisted on developing novel
      hydroxyapatite/chitosan (HA/CS) bilayered scaffold by combining a sintering and a
      freeze-drying technique, and aims to show the potential of such type of scaffolds
      for being used in TE of osteochondral defects. The developed HA/CS bilayered
      scaffolds were characterized by Fourier transform infra-red spectroscopy, X-ray
      diffraction analysis, micro-computed tomography, and scanning electron microscopy
      (SEM). Additionally, the mechanical properties of HA/CS bilayered scaffolds were
      assessed under compression. In vitro tests were also carried out, in order to
      study the water-uptake and weight loss profile of the HA/CS bilayered scaffolds.
      This was done by means of soaking the scaffolds into a phosphate buffered saline
      for 1 up to 30 days. The intrinsic cytotoxicity of the HA scaffolds and HA/CS
      bilayered scaffolds extract fluids was investigated by carrying out a cellular
      viability assay (MTS test) using Mouse fibroblastic-like cells. Results have
      shown that materials do not exert any cytotoxic effect. Complementarily, in vitro
      (phase I) cell culture studies were carried out to evaluate the capacity of HA
      and CS layers to separately, support the growth and differentiation of goat
      marrow stromal cells (GBMCs) into osteoblasts and chondrocytes, respectively.
      Cell adhesion and morphology were analysed by SEM while the cell viability and
      proliferation were assessed by MTS test and DNA quantification. The chondrogenic
      differentiation of GBMCs was evaluated measuring the glucosaminoglycans
      synthesis. Data showed that GBMCs were able to adhere, proliferate and osteogenic
      differentiation was evaluated by alkaline phosphatase activity and
      immunocytochemistry assays after 14 days in osteogenic medium and into
      chondrocytes after 21 days in culture with chondrogenic medium. The obtained
      results concerning the physicochemical and biological properties of the developed
      HA/CS bilayered scaffolds, show that these constructs exhibit great potential for
      their use in TE strategies leading to the formation of adequate tissue
      substitutes for the regeneration of osteochondral defects.

PMID- 16945411
TI  - Response of micro- and macrovascular endothelial cells to starch-based fiber
      meshes for bone tissue engineering.
AB  - The establishment of a functional vasculature is as yet an unrealized milestone
      in bone reconstruction therapy. For this study, fiber-mesh scaffolds obtained
      from a blend of starch and poly(caprolactone) (SPCL), that have previously been
      shown to be an excellent material for the proliferation and differentiation of
      bone marrow cells and thereby represent great potential as constructs for bone
      regeneration, were examined for endothelial cell (EC) compatibility. To be
      successfully applied in vivo, this tissue engineered construct should also be
      able to support the growth of ECs in order to facilitate vascularization and
      therefore assure the viability of the construct upon implantation. The main goal
      of this study was to examine the interactions between ECs and SPCL fiber meshes.
      Primary cultures of HUVEC cells were selected as a model of macrovascular cells
      and the cell line HPMEC-ST1.6R as a model for microvascular ECs. Both macro- and
      microvascular ECs adhered to SPCL fiber-mesh scaffolds and grew to cover much of
      the available surface area of the scaffold. In addition, ECs growing on the SPCL
      fibers exhibited a typical morphology, maintained important functional
      properties, such as the expression of the intercellular junction proteins, PECAM
      1 and VE-cadherin, the expression of the most typical endothelial marker vWF and
      sensitivity to pro-inflammatory stimuli, as shown by induction of the expression
      of cell adhesion molecules (CAMs) by lipopolysaccharide (LPS). These data
      indicate that ECs growing on SPCL fiber-mesh scaffolds maintain a normal
      expression of EC-specific genes/proteins, indicating a cell compatibility and
      potential suitability of these scaffolds for the vascularization process in bone
      tissue engineering in vivo.

PMID- 16945412
TI  - Differences in the effect on neural stem cells of fetal bovine serum in substrate
      coated and soluble form.
AB  - The influence of fetal bovine serum (FBS) adsorbed to poly(ethylene-co-vinyl
      alcohol) (EVAL) and polyvinyl alcohol (PVA) substrates (coated FBS) and FBS
      present in the culture medium (soluble FBS) on the behavior of embryonic rat
      cerebral cortical neural stem cells was studied at neurosphere level. When both
      coated FBS and soluble FBS were not present in the culture system, the fate and
      behavior of neurospheres were mediated mainly by the substrates used. When
      neurospheres were cultured either on FBS-coated EVAL or FBS-coated PVA substrates
      in the serum-free medium, the most striking morphological characteristic of
      neurospheres was that these neurosphere-forming cells attached and were induced
      to differentiate into process-bearing cell phenotypes predominantly; however, the
      differentiated cell phenotypes were dissimilar on these two substrates. On the
      contrary, when neurospheres were cultured in the medium containing 10% FBS, the
      neurosphere-forming cells were induced into protoplasmic cells typically but no
      difference in differentiated cell phenotypes on EVAL and PVA substrates was
      observed. Interestingly, instead of promoting process outgrowth under serum-free
      medium condition, coated FBS enhanced migration of differentiated protoplasmic
      cells when soluble FBS were present. These results inform that the substrates,
      coated serum, and soluble serum within the culture environment together can
      significantly alter cell behavior and morphological differentiation and will
      therefore be an important clue for the development of biomaterials to regulate
      the potential of the CNS neural stem cells.

PMID- 16945413
TI  - Bortezomib and extramedullary disease in multiple myeloma: the shine and dark
      side of the moon.

PMID- 16945414
TI  - The effect of total-ABL, GUS and B2M control genes on BCR-ABL monitoring by real
      time RT-PCR.
AB  - We compared the effect of control genes (CG): total Abelson (total-ABL), beta-2
      microglobulin (B2M) and beta-glucuronidase (GUS), recommended in the Europe
      Against Cancer (EAC) program, on real-time BCR-ABL monitoring in patients with
      chronic myeloid leukemia (CML). We focused on the stability of CG expressions
      during therapy and the effect of the CGs on BCR-ABL ability to characterize the
      disease status and disease prognosis, issues that have not been addressed yet.
      The results showed B2M as a very convenient CG for BCR-ABL monitoring. On the
      contrary, the widely used total-ABL was not confirmed as appropriate for
      normalization of gene expression in CML.

PMID- 16945415
TI  - Binding of alkylphenols and alkylated non-phenolics to the rainbow trout
      (Oncorhynchus mykiss) plasma sex steroid-binding protein.
AB  - Alkylphenols are well-known endocrine disrupters, mediating effects through the
      estrogen receptor (ER). Although the estrogenic properties of the alkylphenols
      are well documented, alternative mechanisms of action are poorly described. In
      the present work, the interaction of a range of alkyl-substituted phenols and
      alkyl-substituted non-phenolics with the rainbow trout (Oncorhynchus mykiss) sex
      steroid-binding protein (rtSBP) were determined by competitive ligand-binding
      studies. The role of alkyl chain length and branching, substituent position,
      number of alkylated groups, and the requirement of a phenolic ring structure were
      assessed. The results showed that the rtSBP binds to most chemical structures
      tested, although the highest affinity was obtained for mono-substituted
      alkylphenols with a chain length of four to eight methyl groups. Interestingly,
      rtSBP binding was also observed for non-phenolic compounds such as 4-t
      butylcyclohexanol and 4-t-butylnitrobenzene suggesting that the rtSBP has a broad
      binding specificity for alkylphenols and alkylated non-phenolics.

PMID- 16945416
TI  - Cloning and sequencing of the Bet v 1-homologous allergen Fra a 1 in strawberry
      (Fragaria ananassa) shows the presence of an intron and little variability in
      amino acid sequence.
AB  - The Fra a 1 allergen in strawberry (Fragaria ananassa) is homologous to the major
      birch pollen allergen Bet v 1, which has numerous isoforms differing in terms of
      amino acid sequence and immunological impact. To map the extent of sequence
      differences in the Fra a 1 allergen, PCR cloning and sequencing was applied.
      Several genomic sequences of Fra a 1, with a length of either 584, 591 or 594
      nucleotides, were obtained from three different strawberry varieties. All
      contained one intron, with the length of either 101 or 110 nucleotides. By
      sequencing 30 different clones, eight different DNA sequences were obtained,
      giving in total five potential Fra a 1 protein isoforms, with high sequence
      similarity (>97% sequence identity) and only seven positions of amino acid
      variability, which were largely confirmed by mass spectrometry of expressed
      proteins. We conclude that the sequence variability in the strawberry allergen
      Fra a 1 is small, within and between strawberry varieties, and that multiple
      spots, previously detected in 2DE, are presumably due to differences in post
      translational modification rather than differences in amino acid sequence. The
      most abundant Fra a 1 isoform sequence, recombinantly expressed in Escherichia
      coli after removal of the intron, was recognized by IgE from strawberry allergic
      patients. It cross-reacted with antibodies to Bet v 1 and the homologous apple
      allergen Mal d 1 (61 and 78% sequence identity, respectively), and will be used
      in further analyses of variation in Fra a 1-expression.

PMID- 16945417
TI  - Cisplatin modulates voltage gated channel currents of dorsal root ganglion
      neurons of rats.
AB  - The anticancer drug cis-diammindichloroplatin (CDDP, cisplatin) causes severe
      side effects like peripheral sensitive neuropathy. The toxicity of CDDP has been
      linked to changes in intracellular calcium homeostasis ([Ca2+]i). Voltage
      activated calcium channel currents (ICa(V)) are important for the regulation of
      [Ca2+]i; therefore, this study was designed to examine the effect of CDDP on
      ICa(V) in comparison to voltage activated potassium (IK(V)) and sodium (INa(V))
      channel currents using the whole cell patch clamp method on dorsal root ganglion
      neurons of rats. In small neurons (<or=O20 microm) CDDP reduced peak and
      sustained ICa(V) concentration dependently (1-100 microM). The IC50 was 23.9+/
      4.5 microM (+/-S.D.) for the peak current with a Hill-coefficient of 0.6+/-0.1
      and 38.8+/-6.1 microM for the sustained current (Hill-coefficient: 0.7+/-0.1).
      IK(V) were reduced by 20.9+/-4.8% (10 microM) and INa(V) were only reduced by
      9.2%+/-7.2% (10 microM). ICa(V) of large neurons (>or=O25 microm) were less
      sensitive to CDDP. The peak ICa(V) was reduced by 14.1+/-2.3% and IK(V) by 12.8+/
      3.4% (100 microM). The sensitivity of INa(V) in large neurons to CDDP was not
      different compared to small neurons. We conclude that the reduction of ICa(V) in
      small cells may be responsible for the neurotoxic side effects CDDP causes in
      sensory neurons.

PMID- 16945419
TI  - Non-invasive intraoperative monitoring of blood pressure and arterial pCO2 during
      surgical anesthesia in mice.
AB  - Despite the constantly increasing use of genetically engineered mice in
      biomedical research, control of crucial physiological parameters such as blood
      pressure and arterial blood gases is difficult to achieve in temporarily
      anesthetized mice due to lack of techniques for reversible arterial cannulation.
      Here we report that arterial blood pressure and blood gases can be measured
      reliably in anaesthetized and artificially ventilated mice using non-invasive
      technology. C57Bl6 mice were anaesthetized by i.p. injection of midazolam,
      fentanyl, and medetomidin, intubated, and ventilated for 3h. End tidal pCO2 was
      monitored by micro-capnometry. Arterial blood pressure was measured non
      invasively using a tail cuff. Non-invasive blood pressure (NIBP) correlated
      strongly with the invasive arterial blood pressure measured at the external
      carotid artery (r = 0.99, P < 0.001) and end tidal pCO2 values correlated very
      well with arterial blood pCO2 (r = 0.93, P < 0.001). The current results
      demonstrate that it is possible to reliably measure and control the most relevant
      physiological parameters in anesthetized mice. Thereby the current study may help
      to reduce animal numbers and perform mice experiments under more defined and
      controlled physiological conditions in the future.

PMID- 16945418
TI  - Leukocyte lipid bodies regulation and function: contribution to allergy and host
      defense.
AB  - Lipid bodies are lipid-rich organelles found in the cytoplasm of a variety of
      cells, including leukocytes. Lipid body morphology, its ability to interact with
      other organelles and its functions are dictated by its lipid arrangement, as well
      as its protein composition. Both may vary according to the cell type and with the
      specific lipid body biogenic stimulatory pathways. Nascent lipid bodies, which
      are formed in vivo in the course of a variety of immunopathological conditions,
      are sites of enzyme localization, eicosanoid production, as well as, sites for
      cytokine storage in inflammatory leukocytes, suggesting that lipid bodies
      function as inducible intracellular platforms for spatial segregation and
      organization of signaling leading to inflammatory mediator secretion during
      inflammation. The emerging role of lipid bodies as inflammatory organelles raises
      lipid body status to critical regulators of different inflammatory diseases, key
      markers of leukocyte activation and attractive targets for novel anti
      inflammatory therapies.

PMID- 16945420
TI  - A delivery device for presentation of tactile stimuli during functional magnetic
      resonance imaging.
AB  - We describe a novel stimulus delivery system designed to present tactile stimuli
      to a subject in the tunnel of a magnetic resonance imaging (MRI) system. Using
      energy from an air-driven piston to turn a wheel, the device advances a conveyor
      belt with a pre-determined sequence of stimuli that differ in their spatial
      features into the tunnel of the MRI. The positioning of one or several stimulus
      objects in a window near the subject's hand is controlled by a photoelectric
      device that detects periodic openings in the conveyor belt. Using this electric
      signal to position each presentation avoids cumulative positioning errors and
      provides a signal related to the progression of the experiment. We used a series
      of shapes that differed in their spatial features but the device could carry
      stimuli with a diversity of shapes and textures. This flexibility allows the
      experimenter to design a wide variety of psychophysical experiments in the haptic
      world and possibly to compare and contrast these stimuli with the cognitive
      treatment of similar stimuli delivered to the other senses. Appropriate
      experimental design allows separation of motor, sensory and memory storage phases
      of mental processes.

PMID- 16945421
TI  - Signal and noise of Fourier reconstructed fMRI data.
AB  - In magnetic resonance imaging, complex-valued measurements are acquired in time
      corresponding to spatial frequency measurements in space generally placed on a
      Cartesian rectangular grid. These complex-valued measurements are transformed
      into a measured complex-valued image by an image reconstruction method. The most
      common image reconstruction method is the inverse Fourier transform. It is known
      that image voxels are spatially correlated. A property of the inverse Fourier
      transformation is that uncorrelated spatial frequency measurements yield
      spatially uncorrelated voxel measurements and vice versa. Spatially correlated
      voxel measurements result from correlated spatial frequency measurements. This
      paper describes the resulting correlation structure between voxel measurements
      when inverse Fourier reconstructing correlated spatial frequency measurements. A
      real-valued representation for the complex-valued measurements is introduced
      along with an associated multivariate normal distribution. One potential
      application of this methodology is that there may be a correlation structure
      introduced by the measurement process or adjustments made to the spatial
      frequencies. This would produce spatially correlated voxel measurements after
      inverse Fourier transform reconstruction that have artificially inflated spatial
      correlation. One implication of these results is that one source of spatial
      correlation between voxels termed connectivity may be attributed to correlated
      spatial frequencies. The true voxel connectivity may be less than previously
      thought. This methodology could be utilized to characterize noise correlation in
      its original form and adjust for it. The exact statistical relationship between
      spatial frequency measurements and voxel measurements has now been established.

PMID- 16945422
TI  - Comparing spectra and coherences for groups of unequal size.
AB  - Spectra and coherences are standard measures of association within and between
      time series. These measures have several advantages over their time-domain
      counterparts, not the least of which is the ability to derive and estimate
      confidence intervals. However, comparing spectra and coherences between two
      groups of observation is a problem that has not received much attention. This
      problem is important in neuroscience since it is often of great interest to
      determine whether the estimates differ between distinct experimental/behavioral
      conditions. Here we propose one approach to this problem. Based on the known
      distributional properties of spectral and coherence estimates, we derive a test
      for equality of two spectral or coherence estimates. The test is applicable to
      unequal sample sizes. We also derive jackknifed estimates of the variance of the
      proposed test statistic. We suggest that comparing the estimates obtained from
      the jackknife procedure with the theoretical estimates provides a robust means of
      determining whether the data in question shows non-Gaussian or non-stationary
      behavior. Finally, we present applications of the method to simulated and real
      data.

PMID- 16945423
TI  - In vivo transcranial imaging of connections in mouse visual cortex.
AB  - From the moment the mouse model took center stage for studies of cortical
      arealization and map formation, there was an urgent need for methods to identify
      areal borders in the living animal. The need was met in part by intrinsic optical
      signal imaging, which has been successfully applied to map topographic
      representations in primary visual, auditory and somatosensory cortex. However,
      the challenge remains to register these maps to the underlying structure. This is
      especially important for studies of the mouse brain in which cortical areas are
      often only a few hundred microns across. Here, we show that in visual cortex
      neuronal tracing with fluororuby and fluoroemerald can be used for transcranial
      imaging through the intact skull of callosal connections from the opposite side
      of the brain, and for mapping of topographic striate-extrastriate cortical
      pathways in living mice. Because callosal connections are important landmarks for
      cortical areas, the new method will allow registration of functional maps to
      underlying structures and facilitate targeted single-unit recordings in
      identified cortical areas.

PMID- 16945425
TI  - Carbohydrate-deficient transferrin and anorexia nervosa.

PMID- 16945424
TI  - Assessing depressive symptoms in persons who die of suicide in mainland China.
AB  - BACKGROUND: The potential insensitivity to depression of translated diagnostic
      instruments makes it difficult to assess the relationship of depressive symptoms
      to suicide in non-Western cultures. METHODS: Addition of culturally sensitive
      probes and other modifications were made to the depression section of the Chinese
      version of the SCID; the standard SCID probes and the expanded-probes are
      separately used to assess each symptom of depression, the resultant diagnoses and
      the overall severity of depression. This modified SCID was included in the
      psychological autopsy interviews with family members and, separately, close
      associates of 887 suicides and 721 non-suicidal decedents from 23 regions of
      mainland China. RESULTS: Compared to the standard interview, the expanded-probe
      method increased reported prevalence of major depressive episode among suicide
      decedents from 26.4% (234/887) to 40.2% (357/887) and for other deaths from 1.0%
      (7/721) to 2.1% (15/701). The additional 131 cases identified using the expanded
      probe method had substantial social impairment and a greatly elevated risk of
      suicide compared to those with no depressive symptoms (OR=37.0, 95% CI=17.6
      77.6). Inter-observer reliability for major depressive episode between the two
      independent interviews was greater for the expanded probe method (ICC=0.77 vs.
      0.67, P<0.001). For both interview methods there was a strong dose-response
      relationship between suicide risk and the number and severity of depressive
      symptoms. LIMITATIONS: This study uses proxy informants to obtain information
      about the psychological status of deceased subjects; the value of this expanded
      probe method for the diagnosis of depression in non-Western cultures needs to be
      confirmed with living subjects. CONCLUSIONS: Adding culture-appropriate probes
      about depressive symptoms to standardized diagnostic instruments identifies many
      Chinese subjects with unrecognized depression. Dimensional measures of depressive
      symptoms are more powerful predictors of suicide risk than categorical diagnoses.

PMID- 16945426
TI  - CD4+ T and B cells cooperate in the immunoregulation of Experimental Autoimmune
      Myasthenia Gravis.
AB  - C57Bl6 mice (B6 mice) immunized with Torpedo acetylcholine receptor (TAChR) in
      Freund's adjuvants (FA) develop Experimental Autoimmune Myasthenia Gravis (EAMG).
      In mouse EAMG Th2 cytokines may be protective. Aluminum hydroxide (Alum) was used
      to immunize B6 mice to the TAChR and prime CD4+ T and B cells secreting Th2
      cytokines. Mice immunized with TAChR/Alum developed anti-AChR CD4+ T cells
      response, but minimal antibody levels and symptoms. TAChR/Alum treatments prior
      immunization with TAChR/FA protected mice from EAMG. Cell transfer experiments
      demonstrated that B and CD4+ T cells mediated the protective effect by causing
      intense reduction of complement-fixing anti-TAChR IgG subclasses.

PMID- 16945427
TI  - Oligoclonal bands in multiple sclerosis cerebrospinal fluid: an update on
      methodology and clinical usefulness.
AB  - Two or more oligoclonal IgG bands (OB) detected by separation of cerebrospinal
      fluid (CSF) proteins while not demonstrable in corresponding serum reflect a
      local B-cell response accompanying central nervous system (CNS) inflammation.
      Using optimized, standardized methodology, preferentially protein separation by
      isoelectric focusing followed by immunoblotting, more than 95% of patients with
      multiple sclerosis (MS) have CSF OB of IgG class not detectable in serum, thereby
      providing powerful evidence for the diagnosis of MS. Once present, CSF OB
      persists in the individual patient irrespective of MS course or therapy. Because
      of the high sensitivity of CSF OB in MS as well as its high specificity in the
      appropriate clinical setting, examination of CSF for OB of IgG class can be
      strongly recommended to obtain support for the diagnosis of MS and identify
      patients with clinically isolated syndrome (CIS) at increased risk of developing
      MS. The IgG index equal to CSF/serum IgG:CSF/serum albumin is elevated in about
      70% of MS patients, but rarely in CSF OB-negative MS. Because of lower diagnostic
      sensitivity, IgG index cannot be recommended as replacement of CSF OB in the
      diagnosis of MS but, when elevated, as additional evidence for an augmented B
      cell response within the CNS that is compatible with MS. Although the clinical
      picture as well as findings from magnetic resonance imaging of the brain and
      spinal cord are essential for an MS diagnosis, this should be re-evaluated in CSF
      OB-negative patients, keeping in mind the many disease entities imitating MS.
      Recommended diagnostic criteria for MS must include definitions of the role of
      lumbar puncture and of clearly specified, optimized and standardized routine CSF
      investigations including for the presence of CSF IgG OB. There is a need for
      concerted long-term follow-up studies of the subgroup of MS patients without CSF
      OB regarding e.g. prognostic and immunologic features. For inclusion in trials of
      disease-modulating drugs, it is recommended that patients with MS or CIS are
      selected regarding presence vs. absence of CSF OB. Development and evaluation of
      new technologies to define local vs. systemic B-cell responses in patients with
      MS or CIS vs. patients with other inflammatory neurological diseases should shed
      new light on the role of CSF OB, which remains enigmatic.

PMID- 16945428
TI  - Neural-endocrine-immune complex in the central modulation of tumorigenesis:
      facts, assumptions, and hypotheses.
AB  - For the precise coordination of systemic functions, the nervous system uses a
      variety of peripherally and centrally localized receptors, which transmit
      information from internal and external environments to the central nervous
      system. Tight interconnections between the immune, nervous, and endocrine systems
      provide a base for monitoring and consequent modulation of immune system
      functions by the brain and vice versa. The immune system plays an important role
      in tumorigenesis. On the basis of rich interconnections between the immune,
      nervous and endocrine systems, the possibility that the brain may be informed
      about tumorigenesis is discussed in this review article. Moreover, the eventual
      modulation of tumorigenesis by central nervous system is also considered.
      Prospective consequences of the interactions between tumor and brain for
      diagnosis and therapy of cancer are emphasized.

PMID- 16945429
TI  - Evidence that vestibular hypofunction affects reading acuity in children.
AB  - OBJECTIVE: Despite reported gaze stability deficits in children with hearing
      impairment and concurrent vestibular hypofunction, the reading difficulties
      reported in this population have not been linked to the gaze instability. The
      purpose of this study was to develop a modified version of the MNREAD chart that
      enabled responses orally or using sign language. METHODS: Seventy-two typically
      developing children and 14 children with sensorineural hearing loss with and
      without vestibular hypofunction participated. We examined: (1) reliability and
      age related changes in reading acuity scores, (2) the effect of vestibular
      hypofunction on reading acuity scores, and (3) the relationship between these
      scores and a test of dynamic visual acuity. RESULTS: The test was reliable (ICC
      (3,2)>or=0.86). Reading acuity scores were significantly worse in children with
      vestibular hypofunction (p<or=0.002). Furthermore, reading acuity scores
      correlated with dynamic not static visual acuity scores (r=0.55, p<0.001).
      CONCLUSIONS: These results imply that the gaze instability due to vestibular
      hypofunction affects reading ability in young children.

PMID- 16945430
TI  - Children and partners of patients with recurrent respiratory papillomatosis have
      no evidence of the disease during long-term observation.
AB  - OBJECTIVE: Recurrent respiratory papillomatosis (RRP) is the most common benign
      neoplasm affecting the larynx and upper respiratory tract. The aim of our study
      was to investigate whether children and partners of patients with RRP develop the
      same disease and to determine whether there is an impact of pregnancy on the
      course of RRP. PATIENTS AND METHODS: Thirty-eight of 42 patients with RRP were
      accepted for a multicenter prospective study in Germany in 21.06.83-12.03.90.
      Mean follow-up duration was 15.3+/-1.8 years. The data of partners of patients
      with RRP was collected during the period of observation and then updated via
      interviews in January 2006. Twenty-nine children and four grandchildren were born
      to 14 patients with RRP. Fifteen of 448 cases of patients with RRP were treated
      in Saint Vladimir Moscow Children's Hospital in Russia in 1988-2003 and analyzed
      retrospectively. Sixteen children and one grandchild were born to 15 patients
      with RRP from Russia. In both studies, the virus type of patients with RRP was
      identified by nested PCR or Southern blot hybridization. Statistical analysis was
      performed using Fisher's exact test (probability value set at p<0.05). RESULTS:
      All children born to patients with RRP were healthy. RRP was not diagnosed in any
      of them on the basis of clinical or histological examination. Four of 45 children
      developed dysphonia, two of them had vocal cord nodules. None of the sexual
      partners of patients has developed RRP during the follow-up period. Pregnancy was
      accompanied by excessive growth of papillomas in all women (100%) with RRP
      associated with HPV type 11, and only in 16.7% of women with RRP associated with
      HPV type 6 (p=0.001). CONCLUSIONS: Patients with RRP are able to have healthy
      children regardless of the stage of the disease. Partners of RRP patients do not
      develop RRP during an observation period of 15 years. Pregnancy has a negative
      impact on the course of RRP and local laryngeal status in patients; it is more
      significant in HPV type 11 associated cases as it is manifested by more rapid
      papillomas growth and more frequent recurrence.

PMID- 16945431
TI  - Antiviral interactions of an HCV polymerase inhibitor with an HCV protease
      inhibitor or interferon in vitro.
AB  - The combinations of Abbott Hepatitis C virus (HCV) polymerase A-782759 with
      either Boehringer Ingelheim HCV NS3 protease inhibitor BILN-2061 or interferon
      (IFN) displayed additive to synergistic relationships over a range of
      concentrations of two-drug combination. Treatment of HCV replicon with A-782759,
      IFN or BILN-2061 for about 16 days resulted in dramatic reductions in HCV RNA
      (5.1, 3.0 and 3.9 log10 RNA copies, respectively). However, none of the compounds
      tested alone lead to replicon RNA reduction to undetectable levels. Ongoing
      replication in the presence of A-782759 or BILN-2061 was associated with the
      appearance of resistant mutations M414T in NS5B and D168V in NS3, respectively.
      In contrast, a combination of A-782759 with BILN-2061 resulted in greater than 7
      logs RNA reduction leading to undetectable replicon RNA after 16 days of
      treatment. Our findings suggest that a monotherapy with either drug alone is
      likely to result in development of resistant mutants. However, a combination
      therapy with polymerase inhibitor has the potential to improve the efficacy of
      IFN or a protease inhibitor alone in vivo, due to the lower likelihood of
      resistance development.

PMID- 16945432
TI  - The subiculum to entorhinal cortex projection is capable of sustaining both short
      and long-term plastic changes.
AB  - The hippocampus communicates with the neocortex via the entorhinal cortex. These
      areas are thought to be critically involved in the consolidation of memories. The
      hippocampus is considered to be the site of association of sensory information,
      which is then laid down for long-term storage in the neocortex. We examined the
      projection from the subiculum to the entorhinal cortex to determine whether it
      could function to transfer this hippocampally-processed information to the
      neocortex. Following stimulation in the subiculum we demonstrate a negative-going
      deflection followed by a positive-going deflection in the entorhinal cortex. This
      projection is capable of short-term plastic changes in the form of PPF. FIn
      addition, we demonstrate that long-term synaptic changes in the form of LTP and
      LTD could be sustained for at least 30min on this pathway. Finally we show that
      PPF changes after LTP and LTD, suggesting that a presynaptic mechanism may be
      involved in both of these pathways.

PMID- 16945433
TI  - The neuroprotective effects of PACAP in monosodium glutamate-induced retinal
      lesion involve inhibition of proapoptotic signaling pathways.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptors are
      present in the retina and exert several distinct functions. PACAP has well-known
      neuroprotective effects in neuronal cultures in vitro and against different
      insults in vivo. Recently we have shown that PACAP is neuroprotective against
      monosodium glutamate (MSG)-induced retinal degeneration. In the present study we
      investigated the possible signal transduction pathways involved in the protective
      effect of intravitreal PACAP administration against apoptotic retinal
      degeneration induced by neonatal MSG treatment. MSG induced activation of
      proapoptotic signaling proteins and reduced the levels of antiapoptotic molecules
      in neonatal retinas. Co-treatment with PACAP attenuated the MSG-induced
      activation of caspase-3 and JNK, inhibited the MSG-induced cytosolic
      translocation of apoptosis inducing factor (AIF) and cytochrome c, and increased
      the level of phospho-Bad. Furthermore, PACAP treatment alone decreased cytosolic
      AIF and cytochrome c levels, while PACAP6-38 increased cytochrome c release,
      caspase-3 and JNK activity and decreased phospho-Bad activity. In summary, our
      results show that PACAP treatment attenuated the MSG-induced changes in apoptotic
      signaling molecules in vivo and suggest that also endogenously present PACAP has
      neuroprotective effects. These results may have further clinical implications in
      reducing glutamate-induced excitotoxicity in several ophthalmic diseases.

PMID- 16945434
TI  - A serine kinase associates with the RAL GTPase and phosphorylates RAL-interacting
      protein 1.
AB  - A kinase activity that phosphorylated myelin basic protein in vitro was detected
      in RalA and RalB immunoprecipitates from human platelets. Protein-protein
      interaction studies using recombinant GST-RalA, GST-RalB and GST-cH-Ras confirmed
      that the kinase specifically associates with the Ral GTPase. The Ral Interacting
      Protein 1 (RIP1), a GTPase Activating Protein (GAP) for Cdc42 and Rac1, was found
      to be the preferred substrate for the Ral Interacting Kinase (RIK). Phosphoamino
      acid analysis demonstrated that RIK phosphorylated serine residue in RIP1. The
      Ral-RIK interaction was not dependent on the guanine nucleotide status of Ral.
      RIK was detected in a variety of rat tissues with testis containing the highest
      and skeletal muscle the lowest activity. In-gel kinase renaturation assay using
      RIP1 as the substrate demonstrated that the kinase activity was associated with
      polypeptides of molecular mass of approximately 36-40 kDa and was detected in
      most rat tissues with a prominent 38 kDa band in testis and a 40 kDa band in
      brain. Human platelets contained a single band of approximately 36 kDa. RIK was
      distinct from MAPKs, CDKs, cyclic AMP dependent protein kinase and
      Ca2+/calmodulin dependent kinases. To demonstrate in vivo interaction, the
      endogenous Ral-RIK complex was isolated using a calmodulin affinity column. The
      Ral-RIK complex co-eluted from this column upon washing with a 13 residue peptide
      that encompasses the calmodulin-binding domain in RalA. The data suggest that RIK
      is a serine specific kinase that phosphorylates RIP1 and is constitutively
      associated with Ral. The current study provides additional support for a link
      between Ral and the Cdc42/Rac1 signalling pathways in the cell.

PMID- 16945435
TI  - Alterations of pressure waveforms along the coronary arteries and the effect of
      microcirculatory vasodilation.
AB  - OBJECTIVES: We sought to investigate the differences of pressure waveforms at a
      distal point of an epicardial coronary artery comparatively to the ostium and to
      assess the effect of microcirculatory vasodilation on them. BACKGROUND: Pressure
      waveforms in the systematic circulation and their alterations along the aorta due
      to wave reflections from the periphery have been extensively studied. However,
      similar data regarding intracoronary pressure waveforms and the effects of
      coronary microcirculation on them are limited. METHODS: In 18 patients who
      underwent diagnostic coronary angiogram or percutaneous coronary intervention in
      the left circumflex or the right coronary artery, we studied pressure waveforms
      recorded by a high-fidelity pressure wire, which was advanced to the ostium and
      to a distal site of the free of significant lesions left anterior descending
      coronary artery. Pressure recording was performed both at rest and at hyperemia
      induced by intravenous infusion of adenosine. Analysis of pressure waveforms at
      the frequency domain was performed with Fast Fourier Transform. RESULTS: At
      baseline conditions, distal pressure waveforms were characterized by higher
      pulsatility, higher presystolic wave and higher amplitude of the 11th to the 15th
      harmonics. Hyperemia increased the pulsatility, compressed the notch and
      decreased the amplitude of higher than the 10th harmonics of distal waveforms.
      CONCLUSIONS: This study identifies differences of pressure waveforms between
      proximal and distal sites of free of significant lesions coronary arteries, which
      are affected by the status of coronary microcirculation and may therefore
      facilitate assessment of microvascular disease.

PMID- 16945436
TI  - Acquired noncompaction?

PMID- 16945437
TI  - Enhanced inflammatory response following coronary stent implantation in stable
      angina patients.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) is associated with an
      increase in inflammatory activity. However, little is known about the association
      between the inflammatory response post-PCI and plaque morphology. The objective
      of this study was to characterize the inflammatory response following coronary
      stent implantation (CSI) of stable atherosclerotic plaques, according to plaque
      morphology. METHODS: The study population consisted of 62 patients with stable
      angina that had an elective indication of CSI. Immediately before CSI, the
      patients underwent intravascular ultrasound (IVUS) for determination of the
      predominant plaque morphology of the target lesion: calcified (C, n=15),
      fibrocalcified (FC, n=16), fibrolipidic (FL, n=16), or lipidic (L, n=15).
      Angiographic lesion types were also determined. Coronary sinus samples were
      collected at baseline (BL) and 15 min after CSI for measuring inflammatory
      mediators (IM): interleukin-6 (IL-6, in pg/ml), tumoral necrosis factor-alpha
      (TNF, in pg/ml), interferon-gamma (IFN, in IU/ml), and neopterin (N, in ng/ml).
      RESULTS: BL IL-6, TNF, IFN, and N were, respectively, for C plaques (mean+/
      S.D.): 1.3+/-3.0, 8.0+/-3.5, 0.1+/-0.2, and 3.2+/-0.8; for FC plaques: 6.7+/-3.3,
      1.9+/-2.0, 0.1+/-0.1, and 3.8+/-2.0; for FL plaques: 0.7+/-0.9, 8.7+/-4.3, 0.1+/
      0.2, and 4.0+/-2.4; and, for L plaques: 1.9+/-2.8, 0.9+/-1.4, 0.0+/-0.1, and
      5.2+/-3.3. After 15 min of CSI, percentual changes of IL-6, TNF, IFN, and N,
      respectively, were for C plaques: 43.8+/-19.6%, 7.7+/-5.5%, -7.5+/-5.3%, and 
      20.0+/-11.2%; for FC plaques: 7.7+/-5.5%, 168.4+/-56.9%, 311.1+/-159.9%, and 0%;
      for FL plaques: 147.5+/-16.1%*, 714.3+/-34.4%*, 116.1+/-9.9%*, and 3000.0+/
      230.0%*; and, for L plaques: 147.7+/-14.4%*, 140.3+/-15.0%*, 131.6+/-11.9%*, and
      2300.0+/-25.9%*. Moreover, B1 (n=28) and B2 (n=32) predominated and resulted in
      significant changes only for IL-6 and IFN, respectively. *P<0.05: 15 min vs BL.
      CONCLUSIONS: These data suggest that stable angina patients with predominant
      lipidic (L and FL) plaques present a greater inflammatory response after CSI in
      than those with predominant calcified (C and FC) plaques.

PMID- 16945438
TI  - Efficient computation of partial expected value of sample information using
      Bayesian approximation.
AB  - We describe a novel process for transforming the efficiency of partial expected
      value of sample information (EVSI) computation in decision models. Traditional
      EVSI computation begins with Monte Carlo sampling to produce new simulated data
      sets with a specified sample size. Each data-set is synthesised with prior
      information to give posterior distributions for model parameters, either via
      analytic formulae or a further Markov Chain Monte Carlo (MCMC) simulation. A
      further 'inner level' Monte Carlo sampling then quantifies the effect of the
      simulated data on the decision. This paper describes a novel form of Bayesian
      Laplace approximation, which can be replace both the Bayesian updating and the
      inner Monte Carlo sampling to compute the posterior expectation of a function. We
      compare the accuracy of EVSI estimates in two case study cost-effectiveness
      models using 1st and 2nd order versions of our approximation formula, the
      approximation of Tierney and Kadane, and traditional Monte Carlo. Computational
      efficiency gains depend on the complexity of the net benefit functions, the
      number of inner level Monte Carlo samples used, and the requirement or otherwise
      for MCMC methods to produce the posterior distributions. This methodology
      provides a new and valuable approach for EVSI computation in health economic
      decision models and potential wider benefits in many fields requiring Bayesian
      approximation.

PMID- 16945439
TI  - Development of a new real-time TaqMan PCR assay for quantitative analyses of
      Candida albicans resistance genes expression.
AB  - Candida albicans is an important opportunistic pathogen that can cause serious
      fungal diseases in immunocompromised patients including cancer patients,
      transplant patients, and patients receiving immunosuppressive therapy in general,
      those with human immunodeficiency virus infections and undergoing major surgery.
      Its emergence spectrum varies from mucosal to systemic infections and the first
      line treatment is still based on fluconazole, a triazole derivate with a potent
      antifungal activity against most of C. albicans strains. Nevertheless the
      emergence of fluconazole-resistant C. albicans strains can lead to treatment
      failures and thus become a clinical problem in the management of such infections.
      For that reason we consider it important to study mechanisms inducing azole
      resistance and the possibilities to influence this process. In this work we give
      a short report on a real-time PCR (TaqMan) assay, which can be used for
      quantitative analyses of gene expression levels of MDR1, CDR1 and ERG11, genes
      supposed to contribute to development of the resistance mechanisms. We show some
      results achieved with that assay in fluconazole susceptible and resistant strains
      that confirm results seen earlier in experiments using Northern blot
      hybridisation and prove that the comparative DeltaCt method is valid for our
      system.

PMID- 16945440
TI  - Transforming growth factor beta mediates apoptosis in the ganglion cell layer
      during all programmed cell death periods of the developing murine retina.
AB  - Transforming growth factor beta (TGF-beta) is an extracellular signaling molecule
      known to mediate programmed cell death (PCD) in the developing retina. In the
      present study, we investigated the expression profiles and activity levels of TGF
      beta ligand and TGF-beta receptors (TbetaR) during the successive physiological
      PCD periods of the developing postnatal mouse retina. The peak of TbetaR
      expression levels--revealed by Western Blots and MLEC assays--coincided with the
      main periods of postnatal (P) retinal murine PCD at P2, P9, and P15.
      Immunocytochemical studies showed that the localization of the TbetaRs is
      restricted to the ganglion cell layer. Application of a neutralizing anti-TGF
      beta antibody to E15 and P9 retinal cultures resulted in a significant decrease
      in the number of TUNEL-positive neurons specifically in the ganglion cell or
      prospective ganglion cell layer. Treatment of P2 and P15 organotypic murine
      retinal wholemount cultures with exogenous recombinant TGF-beta significantly
      increased cell death levels. In the P15 retina, where PCD affects ganglion cells
      and photoreceptors, TGF-beta induced cell death of large retinal ganglion cells,
      whereas small ganglion cells and photoreceptor neurons remained unaffected. Our
      data indicate that TGF-beta mediated apoptosis during all postnatal retinal PCD
      phases specifically affects the fate of retinal ganglion cells.

PMID- 16945441
TI  - Study of the toxic effect of short- and medium-chain monocarboxylic acids on the
      growth of Saccharomyces cerevisiae using the CO2-auxo-accelerostat fermentation
      system.
AB  - The effect of aliphatic monocarboxylic acids (formic, acetic, propionic, valeric,
      octanoic and decanoic acids) on the growth and metabolic activity of
      Saccharomyces cerevisiae S288C was studied, using continuous cultivation method -
      CO(2)-auxo-accelerostat with smooth increase in the concentration of added
      monocarboxylic acids. Slow increase in the concentration of these acids resulted
      in the rapid decrease in the growth yield (Y(ATP)) and specific growth rate
      (micro), however, the specific ATP production rate (Q(ATP)) increased or stayed
      almost constant. On the other hand, Q(ATP) decreased if the concentration of
      formic, acetic or decanoic acids was increased rapidly. The toxic effect of
      aliphatic monocarboxylic acids on the growth of S. cerevisiae was characterized
      and quantified from the respective dose-effect curves as the IC(50) value (mM)
      using two different endpoints: a decrease of 50% in the specific growth rate
      (IC(50 micro)) and a decrease of 50% in the growth yield based on ATP production
      (IC(50YATP)). The concentrations of formic, acetic, propionic, valeric, octanoic
      and decanoic acids causing the 50% reduction in the specific growth rate (IC(50
      micro)) were, respectively, 18.1, 47.1, 33.6, 2.3, 0.16 and 0.07 mM. The IC(50
      micro) values were notably lower (up to 5-fold) in case of a more rapid increase
      in the concentration of acid in the medium. The results of the CO(2)-auxo
      accelerostat experiments show that the toxic effect depends not only on the
      nature of the monocarboxylic acid (lipophilicity) but also on the rate at which
      its concentration changes in the growth environment.

PMID- 16945442
TI  - Solid-state production of polygalacturonase by Aspergillus sojae ATCC 20235.
AB  - The effect of solid substrates, inoculum and incubation time were studied using
      response surface methodology (RSM) for the production of polygalacturonase enzyme
      and spores in solid-state fermentation using Aspergillus sojae ATCC 20235. Two
      stage optimization procedure was applied using D-optimal and face-centered
      central composite design (CCD). Crushed maize was chosen as the solid substrate,
      for maximum polygalacturonase enzyme activity based on D-optimal design. Inoculum
      and incubation time were determined to have significant effect on enzyme activity
      and total spore (p<0.01) based on the results of CCD. A second order polynomial
      regression model was fitted and was found adequate for individual responses. All
      two models provided an adequate R(2) of 0.9963 (polygalacturonase) and 0.9806
      (spores) (p<0.001). The individual optimum values of inoculum and incubation time
      for maximum production of the two responses were 2 x 10(7) total spores and 5-6
      days. The predicted enzyme activity (30.55 U/g solid) and spore count (2.23 x
      10(7)spore/ml) were very close to the actual values obtained experimentally
      (29.093 U/g solid and 2.31 x 10(7)spore/ml, respectively). The overall optimum
      region considering the two responses together, overlayed with the individual
      optima. Solid-state fermentation provided 48% more polygalacturonase activity
      compared to submerged fermentation under individually optimized conditions.

PMID- 16945443
TI  - Inclusion body anatomy and functioning of chaperone-mediated in vivo inclusion
      body disassembly during high-level recombinant protein production in Escherichia
      coli.
AB  - During production in recombinant Escherichia coli, the human basic fibroblast
      growth factor (hFGF-2) partly aggregates into stable cytoplasmic inclusion
      bodies. These inclusion bodies additionally contain significant amounts of the
      heat-shock chaperone DnaK, and putative DnaK substrates such as the elongation
      factor Tu (ET-Tu) and the metabolic enzymes dihydrolipoamide dehydrogenase
      (LpdA), tryptophanase (TnaA), and d-tagatose-1,6-bisphosphate aldolase (GatY).
      Guanidinium hydrochloride induced disaggregation studies carried out in vitro on
      artificial aggregates generated through thermal aggregation of purified hFGF-2
      revealed identical disaggregation profiles as hFGF-2 inclusion bodies indicating
      that the heterogenic composition of inclusion bodies did not influence the
      strength of interactions of hFGF-2 in aggregates formed in vivo as inclusion
      bodies compared to those generated in vitro from native and pure hFGF-2 through
      thermal aggregation. Compared to unfolding of native hFGF-2, higher
      concentrations of denaturant were required to dissolve hFGF-2 aggregates showing
      that more energy is required for disruption of interactions in both types of
      protein aggregates compared to the unfolding of the native protein. In vivo
      dissolution of hFGF-2 inclusion bodies was studied through coexpression of
      chaperones of the DnaK and GroEL family and ClpB and combinations thereof. None
      of the chaperone combinations was able to completely prevent the initial
      formation of inclusion bodies, but upon prolonged incubation mediated
      disaggregation of otherwise stable inclusion bodies. The GroEL system was
      particularly efficient in inclusion body dissolution but did not lead to a
      corresponding increase in soluble hFGF-2 rather was promoting the proteolysis of
      the recombinant growth factor. Coproduction of the disaggregating DnaK system and
      ClpB in conjunction with small amounts of the chaperonins GroELS was most
      efficient in disaggregation with concomitant formation of soluble hFGF-2. Thus,
      fine-balanced coproduction of chaperone combinations can play an important role
      in the production of soluble recombinant proteins with a high aggregation
      propensity not through prevention of aggregation but predominantly through their
      disaggregating properties.

PMID- 16945444
TI  - Excess sludge reduction induced by Tubifex tubifex in a recycled sludge reactor.
AB  - Sludge reduction in a conventional activated sludge (CAS) process combined with a
      recycled sludge reactor where Tubifex tubifex (one of Oligochaeta) was inoculated
      was investigated in this study. The results showed sludge production could be
      reduced through T. tubifex's predation on sludge in the recycled sludge reactor.
      The sludge reduction rate of T. tubifex (R) was from 0.18 to 0.81 mg-VSS mg
      Tubifex(-1) d(-1). The sludge reduction capacity of the recycled sludge reactor E
      was from 650 to 1080 mg-VSS L(-1) d(-1). The optimum density of T. tubifex was
      2500 mg L(-1) and the optimum sludge recycled ratio was 1. The existence of T.
      tubifex did not affect COD and NH(4)(+)-N removals in the process, but led to a
      slight decrease in TP removal. SVI almost did not change when the T. tubifex
      density was lower than 3300 mg L(-1). The LC50 values on T. tubifex of copper and
      ammonia were 2.5 and 880 mg L(-1), respectively, both of which were higher than
      those on Aeolosoma hemprichi.

PMID- 16945445
TI  - Impact of RNA degradation on gene expression profiles: assessment of different
      methods to reliably determine RNA quality.
AB  - DNA microarray technology enables investigators to measure the expression of
      several 1000 mRNA species simultaneously in a biological specimen. However, the
      reliability of the microarray technology to detect transcriptional differences
      representative of the original samples is affected by the quality of the
      extracted RNA. Thus, it is of critical importance to standardize sample-handling
      protocols and to perform a quality assessment of RNA preparations. In this
      report, 59 human tissue samples were used to evaluate the relationships between
      RNA quality and gene expression. From Affymetrix GeneChip array data analysis of
      these samples, we compared the performance of the 28S/18S ratio, two computer
      methods (RIN and degradometer) and our in-house RNA quality scale (RQS) in
      assessing RNA quality. The optimal RNA reliability threshold was determined for
      each method using statistical discrimination measures. We showed that RQS, RIN
      and degradometer have a similar capacity to detect reliable RNA samples whereas
      the 28S/18S ratio leads to a misleading categorization. Furthermore, we developed
      a new approach, based on clustering analyses of full chip expression, to control
      RNA quality after hybridization experiments. The combination of these methods,
      allowing monitoring of RNA quality prior to and after the hybridization
      experiments, ensured reliable and reproducible microarray data.

PMID- 16945446
TI  - [Outcome of the Aquitaine Unit for Evaluation, Training and Social and Vocational
      Counselling (UEROS) at 5-year follow-up in young adults with brain damage].
AB  - INTRODUCTION: Difficulties in social and vocational adjustment are common in
      adults with brain damage. A French government-funded program, UEROS (Unit for
      Evaluation, Training and Social and Vocational Counselling), was developed to
      improve cognitive adjustment, social autonomy and return to work for these
      people. OBJECTIVES: To describe the outcome and satisfaction with life after 5
      years for patients who participated in the UEROS-Aquitaine network program. MAIN
      OUTCOME MEASURES: EBIS Document to evaluate people with traumatic brain injury.
      RESULTS: Seventy-five of the 102 patients participating in UEROS from 1997 to
      1999 were assessed during a phone-structured interview based on the EBIS
      Document. The sample consisted of young adults (mean age 28.5 years), most (65,
      85%) with brain injury and moderate disability (Glasgow Outcome Scale 2: 57%) or
      severe disability (Glasgow Outcome Scale 3: 42%). On entering the program, 33% of
      the subjects needed no help physically or cognitively. None were employed. At the
      end of the program, 9% were students or were learning a job, 8% worked full-time,
      16% were in sheltered conditions, and 13% had volunteer activities. At 5-year
      follow-up, 50% of the subjects were independent, 4% were in school, 10.6% worked
      full-time, and 26.7% were in sheltered conditions. Playing sports was associated
      with good social adjustment. The professional status at 5 years was significantly
      correlated with following the UEROS program (r=0.30, P<0.01) and status at the
      end of the program (r=0.29, P<0.05). However, 41.3% of the subjects were still
      unsatisfied with their conditions of life. DISCUSSION-CONCLUSION: In patients
      with brain damage, the UEROS-Aquitaine network program improves independence in
      daily living and allows for nearly one inactive adult in two (42%) to be engaged
      in an activity or a job.

PMID- 16945447
TI  - Waist circumference estimation from BMI in Japanese children.
AB  - Waist circumference, not BMI, is one of the factors in the definition of
      metabolic syndrome in adults. In children, waist circumference is also a well
      known predictor of metabolic syndrome. However, waist circumference measurement
      is not as commonly recorded as weight and height measurements in physical
      examinations in schools. This means BMI data is available for every child, but
      waist circumference is not. Therefore, we investigated whether there is an
      alternative way to estimate waist circumference even in those children whose
      waist circumference measurement has not been taken. We evaluated the relationship
      between BMI and the waist circumference of schoolchildren using a relatively
      large-scale population-based cohort in Japan. There was a significant linear
      relationship between BMI and waist circumference noted in each age- and sex
      divided group [9-10-year-old boys: waist=13.99+2.63BMI (r=0.940, p<0.001), 9-10
      year-old girls: waist=15.09+2.61BMI (r=0.933, p<0.001), 12-13-year-old boys:
      waist=23.67+2.22BMI (r=0.880, p<0.001), 12-13-year-old girls: waist=23.83+2.15BMI
      (r=0.859, p<0.001)]. This means it is possible to estimate waist circumference
      from height and weight, at least among those age groups of children in Japan.
      This estimation could be an alternative way and useful in detecting childhood
      metabolic syndrome or obesity disease in which a waist circumference figure is
      necessary.

PMID- 16945448
TI  - Hemodynamic and oxidative stress profile after exercise in type 2 diabetes.
AB  - This study investigated the effect of an acute bout of exercise (>85% VO2Max) on
      biochemical, hemodynamic and oxidative stress variables in sedentary and
      physically active subjects with type 2 diabetes (T2D). Blood measurements were
      taken before and after a treadmill test on 12 sedentary non-diabetes subjects
      (ND), 12 sedentary type 2 diabetes (T2S) and 9 physically active T2D subjects
      (T2DA). T2DS subjects before and after the treadmill test showed a higher plasma
      glucose (123.2 +/- 19.0 mg/dL versus 108.9 +/- 16.8 mg/dL, p < 0.001), HbA1C (8.7
      +/- 2.4% versus 7.3 +/- 1.2%, p < 0.001) and body fat% (21.3 +/- 5.7% versus 34.6
      +/- 4.5%, p < 0.001) than T2DA subjects. T2DA had higher VO2Max (37.7 +/- 3.5
      versus 29.5 +/- 3.2, p < 0.05), time on treadmill (22.3 +/- 2.1 min versus 16.1
      +/- 2.1 min, p < 0.05), hemoglobin (17.9 +/- 0.9 g/dL, p < 0.05) and lower blood
      pressure levels in comparison to ND and T2DS subjects. Thiobarbituric acid
      substances (TBARS) in T2DS were higher than in T2DA subjects (0.27 +/- 0.1
      nmol/mL versus 0.21 +/- 0.1 nmol/mL, p < 0.05). Glutathione (GSH) levels were
      similar among the groups. Physically active type 2 diabetes subjects had a more
      favorable biochemical, hemodynamic and oxidative stress profile than sedentary
      subjects. The coexistence of a poor cardiopulmonary performance and high
      oxidative stress environment can determine a profile of high risk for serious
      cardiovascular events in patients with diabetes.

PMID- 16945449
TI  - Impact of a generic substitution reform on patients' and society's expenditure
      for pharmaceuticals.
AB  - Sweden's pharmaceutical expenditure has increased during the last decades. On 1
      October 2002 mandatory generic substitution was introduced in Sweden with the
      purpose to reduce the growth in pharmaceutical expenditure. The aim of the
      present study was to investigate if the implementation of generic substitution
      was associated with changes in patients' expenses and reimbursed cost for
      prescribed pharmaceuticals included in the Swedish Pharmaceutical Benefits Scheme
      (PBS). Monthly pharmacy sales data was obtained from the National Corporation of
      Swedish Pharmacies (Apoteket AB). The study period ranged between 1 January 2000
      and 31 December 2004. Changes in pharmaceutical expenditure associated with the
      introduction of generic substitution were analysed with a linear segmented
      regression. The study comprised outpatient prescription pharmaceuticals
      encompassed by PBS for Sweden in total and each county council. Two different
      data sets were analysed. The first comprised all prescribed pharmaceuticals. The
      second contained only pharmaceuticals on regular prescriptions (i.e. exclusion of
      multidose dispensed drugs). Changes in patient co-payment per 1000 inhabitants
      and working day and subsidised cost per 1000 inhabitants and working day
      associated with the introduction of generic substitution were analysed.
      Expenditure was expressed in Swedish krona, SEK (SEK 1=US$ 0.14/euro 0.11, 7 July
      2006). The Swedish Consumer Price Index was used to inflation-adjust expenditures
      with 2004 as base. The introduction of generic substitution was associated with a
      significant change in slope for patient co-payment in both all prescribed
      pharmaceuticals and pharmaceuticals on regular prescriptions (p<0.005) for Sweden
      in total. The slope shifted direction from a slight increase before the reform
      into a decline after the reform was implemented. This was also found for the
      average slope of patient co-payment for all county councils (p<0.0001). The
      introduction of generic substitution was associated with a statistically
      significant shift in slope for subsidised cost for Sweden in total (p<0.001). The
      slope shifted from a monthly increase before October 2002 to a monthly decline
      for all prescribed pharmaceuticals afterwards. Similar results were found for the
      average slope of subsidised cost for all county councils both for all prescribed
      pharmaceuticals and pharmaceuticals on regular prescriptions (p<0.0001). The
      introduction of generic substitution was associated with a shift in trend from an
      increase into a decrease both for patients' and society's expenditures. This
      suggests that generic substitution has contributed to a reduction in the growth
      of pharmaceutical expenditure.

PMID- 16945450
TI  - Tracer test with As(V) under variable redox conditions controlling arsenic
      transport in the presence of elevated ferrous iron concentrations.
AB  - To study transport and reactions of arsenic under field conditions, a small-scale
      tracer test was performed in an anoxic, iron-reducing zone of a sandy aquifer at
      the USGS research site on Cape Cod, Massachusetts, USA. For four weeks, a stream
      of groundwater with added As(V) (6.7 muM) and bromide (1.6 mM), was injected in
      order to observe the reduction of As(V) to As(III). Breakthrough of bromide (Br(
      )), As(V), and As(III) as well as additional parameters characterizing the
      geochemical conditions was observed at various locations downstream of the
      injection well over a period of 104 days. After a short lag period, nitrate and
      dissolved oxygen from the injectate oxidized ferrous iron and As(V) became bound
      to the freshly formed hydrous iron oxides. Approximately one week after
      terminating the injection, anoxic conditions had been reestablished and increases
      in As(III) concentrations were observed within 1 m of the injection. During the
      observation period, As(III) and As(V) were transported to a distance of 4.5 m
      downgradient indicating significant retardation by sorption processes for both
      species. Sediment assays as well as elevated concentrations of hydrogen reflected
      the presence of As(V) reducing microorganisms. Thus, microbial As(V) reduction
      was thought to be one major process driving the release of As(III) during the
      tracer test in the Cape Cod aquifer.

PMID- 16945451
TI  - Characterization of contryphans from Conus loroisii and Conus amadis that target
      calcium channels.
AB  - Distinctly different effects of two closely related contryphans have been
      demonstrated on voltage-activated Ca(2+) channels. The peptides Lo959 and Am975
      were isolated from Conus loroisii, a vermivorous marine snail and Conus amadis, a
      molluscivore, respectively. The sequences of Lo959 and Am975 were deduced by mass
      spectrometric sequencing (MALDI-MS/MS) and confirmed by chemical synthesis. The
      sequences of Lo959, GCP(D)WDPWC-NH(2) and Am975, GCO(D)WDPWC-NH(2) (O: 4-trans
      hydroxyproline: Hyp), differ only at residue 3; Pro in Lo959, Hyp in Am975, which
      is identical to contryphan-P, previously isolated from Conus purpurascens, a
      piscivore; while Lo959 is a novel peptide. Both Lo959 and Am975 undergo slow
      conformational interconversion under reverse-phase chromatographic conditions, a
      characteristic feature of all contryphans reported thus far. Electrophysiological
      studies performed using dorsal root ganglion neurons reveal that both peptides
      target high voltage-activated Ca(2+) channels. While Lo959 increases the Ca(2+)
      current, Am975 causes inhibition. The results establish that subtle sequence
      effects, which accompany post-translational modifications in Conus peptides, can
      have dramatic effects on target ion channels.

PMID- 16945453
TI  - Critical thinking as an outcome of context-based learning among post RN students:
      a literature review.
AB  - Increasingly complex needs and expanding roles in the delivery of health care
      require professional nurses to be capable critical thinkers and self-directed
      learners. Problem-based learning (PBL) is promoted as a mean to facilitate
      critical thinking (CT) in nursing students attending generic and post RN
      baccalaureate programs. The authors summarize and analyze nursing research and
      theoretical literature (1992-2005) related to four key topic areas: critical
      thinking, nursing education, PBL, and post RN education, to determine what is
      known about the impact of PBL on CT among post RN students. CINAHL, ERIC, Medline
      and PsychINFO databases were searched and based on the literature retrieved,
      there is no strong research evidence to suggest changes occur in baccalaureate
      nursing students' CT during their educational programs, including those using
      PBL. Similar results were found among post RN students although the literature on
      this topic is sparse. There is a need for additional research and ongoing
      development of valid and reliable instruments to measure CT in nurses to guide
      teaching and learning strategies that effectively facilitate CT among nursing
      students.

PMID- 16945452
TI  - Valproate and copper accelerate TRH-like peptide synthesis in male rat pancreas
      and reproductive tissues.
AB  - Treatment with valproate (Valp) facilitates the synthesis of TRH-like peptides
      (pGlu-X-Pro-NH(2)) in rat brain where "X" can be any amino acid residue. Because
      high levels of TRH-like peptides occur in the pancreas and pGlu-Glu-Pro-NH(2)
      (Glu-TRH) has been shown to be a fertilization promoting peptide, we hypothesized
      that these peptides mediate some of the metabolic and reproductive side effects
      of Valp. Male WKY rats were treated with Valp acutely (AC), chronically (CHR) or
      chronically followed by a 2 day withdrawal (WD). AC, CHR and WD treatments
      significantly altered TRH and/or TRH-like peptide levels in pancreas and
      reproductive tissues. Glu-TRH was the predominant TRH-like peptide in epididymis,
      consistent with its fertilization promoting activity. Glu-TRH levels in the
      epididymis increased 3-fold with AC Valp. Phe-TRH, the most abundant TRH-like
      peptide in the pancreas, increased 4-fold with AC Valp. Phe-TRH inhibits both
      basal and TRH-stimulated insulin release. Large dense core vesicles (LDCV's)
      contain a copper-dependent enzyme responsible for the post-translational
      processing of precursors of TRH and TRH-like peptides. Copper (500 microM)
      increased the in vitro C-terminal amidation of TRH-like peptides by 8- and 4-fold
      during 24 degrees C incubation of homogenates of pancreas and testis,
      respectively. Valp (7 microM) accelerated 3-fold the processing of TRH and TRH
      like peptide precursors in pancreatic LDCV's incubated at 24 degrees C. We
      conclude that copper, an essential cofactor for TRH and TRH-like peptide
      biosynthesis that is chelated by Valp, mediates some of the metabolic and
      reproductive effects of Valp treatment via acceleration of intravesicular
      synthesis and altered release of these peptides.

PMID- 16945454
TI  - Ginseng and Salviae herbs play a role as immune activators and modulate immune
      responses during influenza virus infection.
AB  - We have investigated the adjuvant roles of common herbal medicines (ginseng,
      Salviae) and their effects on early immune responses during influenza virus
      infection in a mouse model. Intranasal co-administration with inactivated
      influenza virus A (PR8) and ginseng or Salviae extract increased the levels of
      influenza virus specific antibodies and neutralizing activities compared to
      immunization with PR8 alone, and provided protective immunity. Salviae co
      administration significantly enhanced IFN-gamma and IL-2 cytokine producing
      splenocytes while ginseng induced high levels of IL-4 and IL-5 cytokine producing
      cells after challenge infection. Cells expressing an early activation marker CD69
      and levels of a pro-inflammatory cytokine IL-6 were highly elevated in lungs from
      naive mice during challenge virus infection, which might be a mechanism in lung
      inflammation leading to death. In contrast, immunized mice that were co
      administered ginseng or Salviae modulated CD69 expressing immune cells, did not
      produce IL-6, and showed significant enhancement of influenza virus specific IgA
      antibody in lungs after challenge virus infection. Therefore, these results
      indicate that both ginseng and Salviae play a role as mucosal adjuvants against
      influenza virus as well as immuno-modulators during influenza virus infection.

PMID- 16945455
TI  - Vaccine adverse events reported in post-marketing study of the Kitasato Institute
      from 1994 to 2004.
AB  - General physicians, pediatricians and parents realize that serious adverse events
      occur with an extremely rare incidence, but have no information on the incidences
      of vaccine-associated adverse events. A proper understanding of vaccine adverse
      events would be helpful in promoting an immunization strategy. Causal association
      can rarely be determined in adverse events through laboratory examinations. We
      examined the cases reported in the post-marketing surveillance of the Kitasato
      Institute, categorizing them into two groups: allergic reactions and severe
      systemic illnesses. Anaphylactic patients with gelatin allergy after immunization
      with live measles, rubella and mumps monovalent vaccines have been reported since
      1993, but the number of reported cases with anaphylaxis dramatically decreased
      after 1999 when gelatin was removed from all brands of DPT. The incidence of
      anaphylactic reaction was estimated to be 0.63 per million for Japanese
      encephalitis virus (JEV) vaccine, 0.95 for DPT and 0.68 for Influenza vaccine,
      but the causative component has not yet been specified. Among 67.2 million
      immunization practices, 6 cases with encephalitis or encephalopathy, 7 with acute
      disseminated encephalomyelitis (ADEM), 10 with Guillain-Barre syndrome and 12
      with idiopathic thrombocytopenic purpura (ITP) were reported. The wild-type
      measles virus genome was detected in a patient with encephalitis and in two of
      four bone marrow aspirates obtained from ITP after measles vaccination.
      Enterovirus infection was identified in two patients after mumps vaccination (one
      each with encephalitis and ADEM), one patient with encephalitis after
      immunization with JEV vaccine, and one with aseptic meningitis after immunization
      with influenza vaccine. The total estimated incidence of serious neurological
      illness after vaccination was 0.1-0.2 per million immunization practices. We
      found that enterovirus or wild-type measles virus infection was coincidentally
      associated with vaccination in several cases suspected of being vaccine adverse
      events.

PMID- 16945456
TI  - Oral immunogenicity of potato-derived HBsAg middle protein in BALB/c mice.
AB  - The antibodies to preS2 synthetic peptides have been probed to neutralize
      hepatitis B virus (HBV), and also the addition of preS2 sequence could enhance
      the antibody response compared with a conventional vaccine in the non- and low
      responders. Previously, we generated transgenic potatoes expressing middle
      protein, which contains additional 55 amino acid preS2 region at the N-terminus
      of the S protein, of HBV to determine the feasibility of developing a plant
      delivered HBV vaccine. In this study, we monitored the immune response after
      induction of immunoglobulin by boosting and assessed the efficacy of the mucosal
      immune response with regard to generate IgA antibodies. The HBsAg middle protein
      expressed in our transgenic potatoes was well immunized at low antigenic
      quantities in mice and the induced anti-S or anti-preS2 antibodies were sustained
      for the whole period without decrease. Orally delivery of plant-derived HBsAg
      middle protein to mice resulted in fecal anti-S or anti-preS2 as well as serum
      IgG. In addition, we used antibodies induced from the immunized mice with the
      potato-derived rHBsAg in competition assay as competitors to confirm the binding
      ability of preS2 antibodies to surface antigen of hepatitis virus. Anti-preS2
      antibodies induced from immunized mice with transgenic potatoes effectively
      competed with anti-preS2 murine antibody H8 as expected. From these results, the
      inclusion of preS2 antigen to HBV plant vaccine may provide additional protective
      immunity in the HBV prevention.

PMID- 16945457
TI  - Sudden infant death syndrome: no increased risk after immunisation.
AB  - BACKGROUND: Although previous studies have shown either no association between
      immunisation and SIDS or even a decreased risk of SIDS, adverse effects,
      including death, from immunisations continue to cause concern, especially when a
      new vaccine is introduced. METHODS: A large case control study with immunisation
      data on 307 SIDS cases and 971 controls. RESULTS: SIDS cases were immunised less
      frequently and later than controls. Furthermore there was no increased risk of
      SIDS in the 14 days following immunisation. There was no evidence to suggest the
      recently introduced hexavalent vaccines were associated with an increased risk of
      SIDS. CONCLUSIONS: This study provides further support that immunisations may
      reduce the risk of SIDS.

PMID- 16945458
TI  - Toona sinensis extracts induces apoptosis via reactive oxygen species in human
      premyelocytic leukemia cells.
AB  - Toona sinensis (T. sinensis), well known in Taiwan as a traditional Chinese
      medicine, has been shown to exhibit antioxidant effects. In this study,
      therefore, the ability of T. sinensis to induce apoptosis was studied in cultured
      human premyelocytic leukemia HL-60 cells. Treatment of the HL-60 cells with a
      variety of concentrations of the aqueous extracts of T. sinensis (TS extracts)
      (10-75 microg/ml) and gallic acid (5-10 microg/ml), the natural phenolic
      components purified from TS extracts, resulted in dose- and time-dependent
      sequences of events marked by apoptosis, as shown by loss of cell viability and
      internucleosomal DNA fragmentation. Furthermore, apoptosis in the HL-60 cells was
      accompanied by the release of cytochrome c, caspase 3 activation and specific
      proteolytic cleavage of poly (ADP-ribose) polymerase (PARP). This increase in TS
      extracts- and gallic acid-induced apoptosis was also associated with a reduction
      in the levels of Bcl-2, a potent cell-death inhibitor, and an increase in those
      of the Bax protein, which heterodimerizes with and thereby inhibits Bcl-2.
      Interestingly, TS extracts- and gallic acid-induced dose-dependent reactive
      oxygen species (ROS) generation in HL-60 cells. We found that catalase
      significantly decreased TS extracts- or gallic acid-induced cytotoxicity, DNA
      fragmentation, and ROS production, however, slight reduction was observed with
      vitamins C and E. Our results indicate that TS extracts- or gallic acid-induced
      HL-60 apoptotic cell death could be due to the generation of ROS, especially
      H(2)O(2). The data suggest that T. sinensis exerts antiproliferative action and
      growth inhibition on HL-60 cells through apoptosis induction, and, therefore,
      that it may have anticancer properties valuable for application in food and drug
      products.

PMID- 16945459
TI  - Immunosuppression, hepatotoxicity and depression of antioxidant status by
      arecoline in albino mice.
AB  - BACKGROUND: There are about 600 million betel quid chewers in the world. Betal
      quid chewing is one of the major risk factors of hepatocarcinoma, oropharyngeal
      and esophagus cancers. Arecoline, the main Areca alkaloid of the betel nut is
      reported to have cytotoxic, genotoxic and mutagenic effects in various cells. It
      shows strong correlation to the incidence of oral submucosal fibrosis,
      leukoplakia and oral cancer, and has also been found to impose toxic
      manifestations in immune, hepatic and other defense systems of the recipient.
      AIM: The precise molecular mechanisms underlying the toxic effects of arecoline
      deserve investigation. To clarify the action of arecoline on defense systems,
      immune, hepatic and detoxification system were studied in mice. METHOD: Cell
      count and cell cycle of the splenocytes were studied for evaluating cell
      immunity. Liver function test (LFT) was followed by assaying different enzyme
      systems from serum (SGPT, SGOT and ALP) and liver (GST for detoxication enzyme,
      SOD and catalase for antioxidant enzymes and GSH for non-enzymatic antioxidant)
      and by ultrastructural studies of hepatocytes. RESULTS: Here we report that
      arecoline arrested splenic lymphocyte cell cycle at lower concentration with
      induced apoptosis at higher concentration thereby causing immunosuppression in
      arecoline recipients. Besides, it resulted in hepatotoxicity in arecoline
      recipient mice by disrupting the hepatocyte ultrastructure, as judged by liver
      ultrastructural studies that showed decreased nuclear size, RER with profusely
      inflated cysternae and abundance of lipid droplets, and by up regulating
      hepatotoxic marker enzymes (SGOT and SGPT) in serum. Arecoline also caused
      depression of antioxidants, i.e., superoxide dismutase (SOD), catalase, reduced
      glutathione (GSH) and glutathione-S-transferase (GST) that are known to
      neutralize reactive oxygen species. CONCLUSION: All these above-mentioned results
      led us to conclude that arecoline attacks multiple targets to finally generate
      systemic toxicity in mice.

PMID- 16945460
TI  - Cytotoxic effects of S-(dimethylarsino)-glutathione: a putative intermediate
      metabolite of inorganic arsenicals.
AB  - Glutathione (GSH) plays an important role in the metabolism of arsenite and
      arsenate by generating arsenic-glutathione complexes. Although dimethylarsinic
      acid (DMA(V)) is the major metabolite of inorganic arsenicals (iAs) in urine, it
      is not clear how DMA(V) is produced from iAs. In the present study we report that
      S-(dimethylarsino)-glutathione (DMA(III)(SG)), a putative precursor of
      dimethylarsinic acid DMA(V), was unstable in the culture medium without excess
      GSH and generated volatile substances which were highly cytotoxic for both rat
      heart microvascular endothelial cells and HL60, a human leukemia cell line.
      Cytotoxicity of DMA(III)(SG) was higher than that of iAs and its LC(50) value was
      calculated to be 7.8 microM in the endothelial cells. To our surprise
      DMA(III)(SG) effectively killed cells in the neighbor wells of the same multi
      well dish, indicating that volatile toxic compounds generated from DMA(III)(SG)
      in the culture medium. High performance lipid chromatography-inductively coupled
      plasma mass spectrometry (HPLC-ICPMS) analyses suggested that the freshly
      generated volatile compounds dissolved into aqueous solution and formed an
      unstable arsenic compound and the unstable compound was further converted to
      DMA(V). These results suggested that DMA(III)(SG) exerts its cytotoxicity by
      generating volatile arsenicals and is implicated in the metabolic conversion of
      inorganic arsenicals into DMA(V), a major final metabolite of inorganic
      arsenicals in most mammals.

PMID- 16945461
TI  - Evaluation of a new caries detecting dye for primary and permanent carious
      dentin.
AB  - OBJECTIVE: This study evaluated the clinical efficacy of a new caries detecting
      dye using a laser fluorescence device (DIAGNOdent). METHOD: Primary and permanent
      teeth with dentin caries were stained with Caries Check (CC), containing 1% acid
      red in polypropylene glycol (MW=300) or Caries Detector (CD), containing 1% acid
      red in propylene glycol (MW=76). Primary-CC, primary-CD, permanent-CC and
      permanent-CD groups were prepared. In the CC groups, stained dentin was
      completely removed. In the CD groups, pink-stained dentin was retained according
      to the manufacturers' instructions. Cavities before and after caries removal were
      measured with the DIAGNOdent. Data were analyzed using ANOVA and Fisher's PLSD
      multiple comparison test at alpha=0.05. Regression analyses were performed
      between DIAGNOdent readings and scores obtained from the clinical parameters.
      RESULTS: For all groups, there were no significant differences in the DIAGNOdent
      readings before treatment. The DIAGNOdent readings after caries removal were:
      primary-CC (16.0+/-17.6), primary-CD (9.6+/-5.2), permanent-CC (11.0+/-7.0) and
      permanent-CD (7.1+/-3.8). Significant differences were identified between the
      permanent-CC and primary-CD, and permanent-CC and permanent-CD subgroups but not
      for the primary subgroups. Correlation coefficients between DIAGNOdent readings
      and clinical parameters were low. CONCLUSIONS: When dentin stained with Caries
      Check was completely removed, the DIAGNOdent readings were higher than those
      recorded when palely-stained pink dentin was retained with the Caries Detector,
      with significant difference observed for the permanent teeth. Caries Check may be
      used clinically to avoid excessive removal of caries-affected or sound dentin in
      permanent teeth but not in primary teeth.

PMID- 16945462
TI  - Comparison of the ability of different colour indices to assess changes in tooth
      whiteness.
AB  - OBJECTIVES: The study investigates the suitability of different whiteness indices
      and colour parameters in assessing changes in tooth whiteness using a digital
      colour imaging system. METHODS: Forty-six male and female subjects aged 18-70
      years participated in the study and were divided into two groups. The control
      group was given a standard "non-whitening" dentifrice (Colgate Great Regular
      Flavour) and the test group received whitening strips (crest white strips). The
      latter contained 6% hydrogen peroxide and were worn for 30 min twice daily on the
      six maxillary anterior teeth. Digital images of teeth were captured using a Jai
      3CCD digital camera with annular LED illumination array and the data obtained was
      used to calculate colour parameters (L*, a* and b*) and whiteness indices (WIC,
      WIO, W). Colour differences (delta L, delta a, delta b and delta E) and
      differences in whiteness indices were obtained and were compared between the test
      and control groups. Reliability and repeatability of the instrument were checked
      by comparing the digital data to the clinical data and also by comparing data
      obtained from different camera views for the same tooth. RESULTS: The test group
      showed significant changes in the colour parameters and whiteness indices over
      the 2-week period. It also showed significant correlation between the digital
      data obtained from lateral and central camera views for the same teeth. Digital
      data showed a similar trend to that of clinical data. The WIO index demonstrated
      the strongest discrimination between the test and control groups. CONCLUSION: The
      WIO index is appropriate for assessing changes in tooth whiteness. The digital
      imaging system is reproducible and reliable in evaluating changes in whiteness of
      teeth.

PMID- 16945463
TI  - Intracellular sterol transport in eukaryotes, a connection to mitochondrial
      function?
AB  - Eukaryotic cells synthesize sterols in the endoplasmatic reticulum (ER) from
      where it needs to be efficiently transported to the plasma membrane, which
      harbors approximately 90% of the free sterol pool of the cell. Sterols that are
      being taken up from the environment, on the other hand, are transported back from
      the plasma membrane to the ER, where the free sterols are esterified to steryl
      esters. The molecular mechanisms that govern this bidirectional movement of
      sterols between the ER and the plasma membrane of eukaryotic cells are only
      poorly understood. Proper control of this transport is important for normal cell
      function and development as indicated by fatal human pathologies such as Niemann
      Pick type C disease and atherosclerosis, which are characterized by an over
      accumulation of free sterols within endosomal membranes and the ER, respectively.
      Recently, a number of complementary approaches using Saccharomyces cerevisiae as
      a model organism lead to a more precise characterization of the pathways that
      control the subcellular transport of sterols and led to the identification of
      components that directly or indirectly affect sterol uptake at the plasma
      membrane and its transport back to the ER. A genetic approach that is based on
      the fact that yeast is a facultative anaerobic organism, which becomes
      auxotrophic for sterols in the absence of oxygen, resulted in the identification
      of 17 genes that are required for efficient uptake and/or transport of sterols.
      Unexpectedly, many of these genes are required for mitochondrial functions. A
      possible connection between mitochondrial biogenesis and sterol biosynthesis and
      uptake will be discussed in light of the fact that cholesterol transport into the
      inner membranes of mitochondria is a well established sterol transport route in
      vertebrates, where it is required to convert cholesterol into pregnenolone, the
      precursor of steroids.

PMID- 16945464
TI  - Human leukocyte elastase hydrolysis of peptides derived from human elastin exon
      24.
AB  - In normal and pathological tissues, polymorphonuclear leukocyte proteases
      (elastase, cathepsin G and proteinase 3) may generate soluble peptides through
      limited proteolysis of elastin, the main component of mature elastic fibres.
      Elastin-derived peptides display diverse biological activities including cell
      migration, differentiation, proliferation, chemotaxis, tumor progression and up
      regulation of metalloproteinases. To be biologically active, their structures
      must adopt a beta-turn conformation which accommodates to the cell surface
      located elastin binding protein. In this study, we established that human elastin
      exon 24-derived peptides are hydrolysed by leukocyte elastase, when the active
      site is fully occupied (from S(5) to S'(3)). As shown by mass spectrometry
      analyses, a major cleavage site was demonstrated at a Val-Ala bond and a minor
      one at Gly-Val bond. For longer peptides, the hydrolysed fragments could
      themselves be re-hydrolysed. If the shortest fragments do not contain the GxxPG
      sequence known to stimulate cellular effects, some of the intermediates together
      with hydrolysis fragments generated by other proteases such as proteinase 3, may
      possess this motif.

PMID- 16945465
TI  - Hospital-wide physiological surveillance-a new approach to the early
      identification and management of the sick patient.
AB  - Hospitalised patients, who suffer cardiac arrest and require unanticipated
      intensive care unit (ICU) admission or die, often exhibit premonitory
      abnormalities in vital signs. Sometimes, the deterioration is well documented,
      though there is little discernable evidence of intervention. In other cases,
      monitoring and recording of vital signs is infrequent or incomplete. Healthcare
      providers have introduced "track and trigger" systems to allow early
      identification of patients with physiological abnormalities, and rapid response
      teams to facilitate rapid and appropriate management. However, even when "track
      and trigger" systems are used, the recording of vital signs, patient chart
      completion and team activation remain sub-optimal. We have developed a system for
      collecting routine vital signs data at the bedside using standard personal
      digital assistants (PDA). The PDAs act as "thin clients" linked by a wireless
      local area network (W-LAN) to the hospital's intranet system, where raw and
      derived data are integrated with other patient information, e.g., name, hospital
      number, laboratory results. It is possible for raw physiology data, early warning
      scores (EWS), vital signs charts and oxygen therapy records to be made
      instantaneously available to any member of the hospital healthcare team via the W
      LAN or hospital intranet. Early and direct contact with members of the patient's
      primary clinical team or rapid response team can be made through an automated
      alerting system, triggered by the EWS data. The ability to capture physiological
      data at the bedside, and to make these available to anyone with appropriate
      access rights at any time and in any place, should provide previously
      unattainable, clinical and administrative benefits. Analysis of the raw
      physiological data and patient outcomes will also make it possible to validate
      existing and future "track and trigger" systems.

PMID- 16945466
TI  - The effect of cardiopulmonary resuscitation training on psychological variables
      of cardiac rehabilitation patients.
AB  - As a component of cardiac rehabilitation (CR), cardiopulmonary resuscitation
      (CPR) training is widely recommended. These recommendations advocate the
      importance of offering CPR training to cardiac patients' families. Prior research
      examining the effect of CPR training on the cardiac patients spouse or family
      member, suggests that receiving CPR training within a supportive environment such
      as cardiac rehabilitation causes no adverse psychological effects in the family
      members. Patients are often excluded from CPR training due to fears of the
      possible physiological consequences. Conversely, there may be negative
      psychological consequences for patients who are excluded from CPR training.
      Although cardiac patients are at high risk of cardiac arrest themselves this
      should not preclude them from having the ability to help another. The aim of this
      study was to assess the impact on anxiety, depression and perception of control
      (POC) of CPR training for the cardiac patients as an integral part of an 8-week
      phase III Cardiac Rehabilitation Programme. Fifty-eight patients and 54 family
      members or partners attending an 8-week CR programme were offered optional CPR
      training during the final week of the programme. Forty-nine patient subjects were
      evaluated at four time points, using the hospital anxiety and depression scale
      and the control attitudes scale. Seventy-five percent (n = 37) of patients
      participated in the CPR training. Teaching CPR to cardiac patients did not affect
      anxiety levels adversely. There was an overall significant decrease in anxiety
      scores for both patient groups over time (p = 0.0071). Both patient groups showed
      an average moderate level of POC at baseline but the POC level in those who did
      the CPR training continued to increase slightly throughout the study period. If
      the patient agreed to undertake CPR training approximately 61% of their relatives
      or partners also undertook the training, but when the patient did not avail of
      the CPR training only 20% of their relatives or partners participated. Cardiac
      patients would appear to have a desire to learn CPR. It is recommended that
      cardiac patients be involved in CPR training as it poses them no adverse
      psychological consequences and may improve their perception of control. Inclusion
      of the patients in the CPR training may help increase the participation in CPR
      training by cardiac patients' families.

PMID- 16945467
TI  - Public perceptions and experiences of myocardial infarction, cardiac arrest and
      CPR in London.
AB  - INTRODUCTION: The lay public have limited knowledge of the symptoms of myocardial
      infarction ("heart attack"), and inaccurate perceptions of cardiac arrest
      survival rates. Levels of CPR training and willingness to intervene in cardiac
      emergencies are also low. AIMS: To explore public perceptions of myocardial
      infarction and cardiac arrest; investigate perceptions of cardiac arrest survival
      rates; assess levels of training and attitudes towards CPR, and explore the types
      of interventions considered useful for increasing rates of bystander CPR among
      Greater London residents. METHODS: A quantitative interview survey was conducted
      with 1011 Greater London residents. Eight focus groups were also conducted to
      explore a range of issues in greater depth and validate trends that emerged in
      the initial survey. RESULTS: Chest pain was the most commonly recognised symptom
      of "heart attack". Around half of the respondents were aware that a myocardial
      infarction differs from a cardiac arrest, although their ability to explain this
      difference was limited. The majority overestimated that at least a quarter of
      cardiac arrest patients in London survive to hospital discharge. Few participants
      had received CPR training, and most were hesitant about performing the procedure
      on a stranger. CONCLUSIONS: Awareness and knowledge of CPR, and reactions to
      cardiac emergencies, reflect relatively low levels of CPR training in London.
      Publicising cardiac arrest survival figures may be instrumental in prompting
      members of the public to train in CPR and motivating those who have been trained
      to intervene in a cardiac emergency.

PMID- 16945468
TI  - Association between interval between call for ambulance and return of spontaneous
      circulation and survival in out-of-hospital cardiac arrest.
AB  - AIM: To describe the association between the interval between the call for
      ambulance and return of spontaneous circulation (ROSC) and survival in out-of
      hospital cardiac arrest. PATIENTS: All patients suffering an out-of-hospital
      cardiac arrest in whom cardiopulmonary resuscitation (CPR) was started, included
      in the Swedish Cardiac Arrest Registry (SCAR) for whom information about the time
      of calling for an ambulance and the time of ROSC was available. RESULTS: Among
      26,192 patients who were included in SCAR and were not witnessed by the ambulance
      crew, information about the time of call for an ambulance and the time of ROSC
      was available in 4847 patients (19%). There was a very strong relationship
      between the interval between call for an ambulance and ROSC and survival to one
      month. If the interval was less than or equal to 5 min, 47% survived to one
      month. If the interval exceeded 30 min, only 5% (n = 35) survived to one month.
      The vast majority of the latter survivors had a shockable rhythm either on
      admission of the rescue team or at some time during resuscitation. CONCLUSION:
      Among patients who have ROSC after an out-of-hospital cardiac arrest, there is a
      very strong association between the interval between the call for ambulance and
      ROSC and survival to one month. However, even if this delay is very long (> 30
      min after calling for an ambulance), a small percentage will ultimately survive;
      they are mainly patients who at some time during resuscitation have a shockable
      rhythm. The overall percentage of patients for whom CPR continued for more than
      30 min who are alive one month later can be assumed to be extremely low.

PMID- 16945469
TI  - In-hospital cardiac arrest: is outcome related to the time of arrest?
AB  - BACKGROUND: Whether outcome from in-hospital cardiopulmonary resuscitation (CPR)
      is poorer when it occurs during the night remains controversial. This study
      examined the relationship between CPR during the various hospital shifts and
      survival to discharge. METHODS: CPR attempts occurring in a tertiary hospital
      with a dedicated, certified resuscitation team were recorded prospectively
      (Utstein template guidelines) over 24 months. Medical records and patient
      characteristics were retrieved from patient admission files. RESULTS: Included
      were 174 in-hospital cardiac arrests; 43%, 32% and 25% in morning evening and
      night shifts, respectively. Shift populations were comparable in demographic and
      treatment related variables. Asystole (p < 0.01) and unwitnessed arrests (p =
      0.05) were more common during the night. Survival to discharge was poorer
      following night shift CPR than following morning and evening shift CPR (p =
      0.04). When asystole (being synonymous with death) was excluded from the
      analysis, the odds of survival to discharge was not higher for witnessed compared
      to unwitnessed arrest but was 4.9 times higher if the cardiac arrest did not
      occur during the night shift (p = 0.05, logistic regression). The relative risk
      of eventual in-hospital death for patients with return of spontaneous circulation
      (ROSC) following night shift resuscitation was 1.9 that of those with ROSC
      following morning or evening resuscitation (Cox regression). CONCLUSIONS:
      Although unwitnessed arrest is more prevalent during night shift, resuscitation
      during this shift is associated with poorer outcomes independently of witnessed
      status. Further research is required into the causes for the increased mortality
      observed after night shift resuscitation.

PMID- 16945470
TI  - The 2005 compression-ventilation ratio in practice: cycles or time?
AB  - AIM: The purpose of this study was to determine how long it takes rescuers to
      complete five cycles of cardiopulmonary resuscitation (CPR) using a compression
      ventilation (CV) ratio of 30:2. MATERIALS AND METHODS: Twenty subjects, who were
      all members of the medical service at a motor racing circuit and trained in basic
      life support (BLS), were instructed to provide five cycles of CPR with a CV ratio
      of 30:2 using a manikin (Little Anne Adult CPR Manikin, Laerdal, Stavanger,
      Norway). The time taken to deliver the first two breaths and to complete all five
      cycles was recorded. RESULTS: The median time to deliver the first two breaths
      was 7.3 s (IQR 6.5-9.6 s) and the median time to complete five cycles with a CV
      ratio of 30:2 was 105.0 s (IQR 92.0-112 s). Many of the subjects found it
      difficult to count five cycles when using this CV ratio. CONCLUSIONS: Five cycles
      of CPR using a CV ratio of 30:2 takes approximately 1 min 45 s to complete. Using
      this CV ratio, trained individuals find it difficult to count out five cycles of
      CPR. It may be simpler to train individuals to give CPR for a specified time (2
      min) instead of a specific number of cycles.

PMID- 16945471
TI  - Training lay-people to use automatic external defibrillators: are all of their
      needs being met?
AB  - AIMS: We explored the experiences of lay people who have been trained to use
      automatic external defibrillators. The research questions were: (1) How can
      training courses help prepare people for dealing with real life situations? (2)
      Who is ultimately responsible for providing critical incident debriefing and how
      should this be organised? (3) What is the best process for providing feedback to
      those who have used an AED? METHODOLOGY: Fifty-three semi-structured, qualitative
      interviews were conducted, some with those who had been trained and others with
      trainers. Locations included airports, railway stations, private companies and
      first responder schemes. Geographically, we covered Nottinghamshire,
      Lincolnshire, Yorkshire, Staffordshire, Essex and the West Midlands in the UK.
      RESULTS: Our analysis of the data indicates that most people believe scenarios
      based within their place of work were most useful in preparing for 'real life'.
      Many people had not received critical incident debriefing after using an AED.
      There were a variety of systems in place to provide support after an incident,
      many of which were informal. CONCLUSION: Training scenarios should be conducted
      outside the classroom. There should be more focus on critical incident debriefing
      during training and a clear identification of who should provide support after an
      incident. Other issues which were of interest included: (1) people's views on do
      not attempt resuscitation (DNAR); (2) perceived boundaries of responsibility when
      using an AED; (3) when is someone no longer 'qualified' to use an AED?

PMID- 16945472
TI  - Clinical consequences of the introduction of mechanical chest compression in the
      EMS system for treatment of out-of-hospital cardiac arrest-a pilot study.
AB  - AIM: To evaluate the outcome among patients suffering from out-of-hospital
      cardiac arrest (OHCA) after the introduction of mechanical chest compression
      (MCC) compared with standard cardiopulmonary resuscitation (SCPR) in two
      emergency medical service (EMS) systems. METHODS: The inclusion criterion was
      witnessed OHCA. The exclusion criteria were age < 18 years, the following judged
      etiologies behind OHCA: trauma, pregnancy, hypothermia, intoxication, hanging and
      drowning or return of spontaneous circulation (ROSC) prior to the arrival of the
      advanced life support (ALS) unit. Two MCC devices were allocated during six-month
      periods between four ALS units for a period of two years (cluster randomisation).
      RESULTS: In all, 328 patients fulfilled the criteria for participation and 159
      were allocated to the MCC tier (the device was used in 66% of cases) and 169 to
      the SCPR tier. In the MCC tier, 51% had ROSC (primary end-point) versus 51% in
      the SCPR tier. The corresponding values for hospital admission alive (secondary
      end-point) were 38% and 37% (NS). In the subset of patients in whom the device
      was used, the percentage who had ROSC was 49% versus 50% in a control group
      matched for age, initial rhythm, aetiology, bystander-/crew-witnessed status and
      delay to CPR. The percentage of patients discharged alive from hospital after
      OHCA was 8% versus 10% (NS) for all patients and 2% versus 4%, respectively (NS)
      for the patients in the subset (where the device was used and the matched control
      population). CONCLUSION: In this pilot study, the results did not support the
      hypothesis that the introduction of mechanical chest compression in OHCA improves
      outcome. However, there is room for further improvement in the use of the device.
      The hypothesis that this will improve outcome needs to be tested in further
      prospective trials.

PMID- 16945473
TI  - A micelle nucleation model for the interaction of dodecyl sulphate with Lys49
      phospholipases A(2).
AB  - Bothropstoxin-I (BthTx-I) is a Lys49-PLA(2) from the venom of Bothrops
      jararacussu that lacks detectable catalytic activity, yet causes rapid Ca(2+)
      independent membrane damage. With the aim of understanding the interaction
      between BthTx-I and amphiphilic molecules, we have studied the interaction of
      sodium dodecyl sulphate (SDS) with the protein. Circular dichroism and attenuated
      total reflection Fourier-transform infrared spectra of BthTx-I reveal changes in
      the alpha-helical organization of the protein at an SDS/BthTx-I molar ratio of 20
      25. At SDS/BthTx-I ratios of 40-45 the alpha-helices return to a native-like
      conformation, although fluorescence emission anisotropy measurements of 2-amino-N
      hexadecyl-benzamide (AHBA) demonstrate that the total SDS is below the critical
      micelle concentration when this transition occurs. These results may be
      interpreted as the result of SDS accumulation by the BthTx-I homodimer and the
      formation of a pre-micelle SDS/BthTx-I complex, which may subsequently be
      released from the protein surface as a free micelle. Similar changes in the alpha
      helical organization of BthTx-I were observed in the presence of
      dipalmitoylphosphatidylcholine liposomes, suggesting that protein structure
      transitions coupled to organization changes of bound amphiphiles may play a role
      in the Ca(2+)-independent membrane damage by Lys49-PLA(2)s.

PMID- 16945474
TI  - Cleaner production opportunity assessment for a milk processing facility.
AB  - Possible cleaner production (CP) opportunities for a milk processing facility
      were examined in this study. The CP concept and its key tools of implementation
      were used to assess the potential CP opportunities in the facility studied. The
      general production process and its resulting environmental loads were
      investigated by taking possible CP opportunities as the basis of study. The
      methodology developed for CP opportunity assessment in the milk processing
      facility covered two major steps: preparation of checklists to assist auditing
      and CP opportunity assessment, and implementation of the mass-balance analysis.
      For mass-balance analysis, measurements and experimental analysis of the mass
      flows were utilized to determine the inputs and outputs. Prepared checklists were
      utilized to determine waste reduction options that could be implemented. Selected
      opportunities were evaluated considering their environmental benefits and
      economic feasibility. The results of the study indicated that 50% of the service
      water used, 9.3% of the current wastewater (WW) discharge, 65.36% of the chemical
      use and the discharge of 181.9 kg/day of chemical oxygen demand (COD) and 20.7
      kg/day of total suspended solids (TSS) could be eliminated and 19.6% of the
      service water used could be recycled/reused.

PMID- 16945475
TI  - Safety and effectiveness of photoselective vaporization of the prostate (PVP) in
      patients on ongoing oral anticoagulation.
AB  - OBJECTIVES: Ongoing oral anticoagulation (OA) contraindicates transurethral
      electroresection of the prostate. We evaluated the safety and effectiveness of
      photoselective vaporization of the prostate (PVP) in patients on ongoing OA with
      coumarin derivatives, aspirin, or clopidogrel, complaining of symptomatic benign
      prostatic hyperplasia (BPH). METHODS: We evaluated perioperative parameters,
      functional outcome, and adverse events up to 24 mo postoperatively of patients on
      OA, and compared results with 92 men at normal risk without anticoagulant therapy
      undergoing PVP for the same indication (control). RESULTS: Within 40 mo, 116 men
      on OA were included, with 31% (n=36) receiving coumarin derivatives; 61% (n=71),
      aspirin; and 8% (n=9), clopidogrel. Mean prostate volume (62+/-34ml vs. 57+/
      25ml; p=0.289) and mean operation time (67+/-28min vs 63+/-29min; p=0.313) were
      comparable with control. We observed no bleeding complications necessitating
      blood transfusions. Average postoperative decrease of haemoglobin was 8.6% for
      patients on OA versus 8.8% for control. At 3, 6, 12, and 24 mo postoperatively,
      improvement of the International Prostate Symptom Score ranged from 60-70%;
      postvoid residual volume, 80-88%; and average maximum urinary flow rate, 116
      140%, respectively. Postoperative complications were low and comparable with
      control. CONCLUSIONS: PVP is characterized by excellent haemostatic properties
      and very low intraoperative complication rate even in patients on OA. On the
      basis of our perioperative results, we recommend PVP as first-line procedure for
      patients with symptomatic BPH at high risk of bleeding.

PMID- 16945476
TI  - Management of urethrovaginal fistulas.
AB  - OBJECTIVES: Despite the apparent similarity, urethrovaginal fistulas (UVFs) are
      not identical to vesicovaginal defects. Obstetric trauma and vaginal surgery are
      the causes of a majority of urethrovaginal fistulas. METHODS: Careful
      preoperative evaluation is essential for identifying small UVFs or associated
      vesicovaginal fistulas and includes physical examination, cystourethroscopy,
      intravenous pyelography, ultrasonography, and urinalysis, but sometimes the final
      surgical plan can only be decided on after the patient is examined under
      anaesthesia with a metal sound in the urethra. Significant tissue deficit is the
      main characteristic of UVF repair and the minimal space present often does not
      allow placing any additional tissue between the urethral and vaginal walls.
      RESULTS: Seventy-one women (mean age, 43 yr) with UVFs have been treated in our
      clinic. Our results have shown successful closure of the fistula in 90.14% of
      patients after primary surgery and 98.59% after a second operation. Postoperative
      stress urinary incontinence developed in 37 patients (52.11%). We used both
      synthetic and autologous slings for their management. Twenty-two patients
      (59.46%) were cured, 12 (32.43%) were improved, and 3 remained incontinent
      (8.11%). The long-term results of 21 patients with mean follow-up time of 99.6 mo
      show no fistula recurrence. Postoperative bladder outlet obstruction (5.63%) was
      successfully managed by urethral dilation or urethrotomy. CONCLUSIONS: This
      article gives a detailed description of UVF surgical treatment. An attached DVD
      demonstrates one case that includes UVF primary repair, recurrent fistula repair,
      and surgery for continence restoration.

PMID- 16945477
TI  - Initial biopsy outcome prediction--head-to-head comparison of a logistic
      regression-based nomogram versus artificial neural network.
AB  - OBJECTIVES: Nomograms and artificial neural networks (ANNs) represent alternative
      methodologic approaches to predict the probability of prostate cancer on initial
      biopsy. We hypothesized that, in a head-to-head comparison, one of the approaches
      might demonstrate better accuracy and performance characteristics than the other.
      METHODS: A previously published nomogram, which relies on age, digital rectal
      examination, serum prostate-specific antigen (PSA), and percent-free PSA, and an
      ANN, which relies on the same predictors plus prostate volume, were applied to a
      cohort of 3980 men, who were subjected to multicore systematic prostate biopsy.
      The accuracy and the performance characteristics were compared between these two
      approaches. RESULTS: The accuracy of the nomogram was 71% versus 67% for the ANN
      (p=0.0001). Graphical exploration of the performance characteristics demonstrated
      virtually perfect predictions for the nomogram. Conversely, the ANN
      underestimated the observed rate of prostate cancer. CONCLUSIONS: A 4% increase
      in predictive accuracy implies that the use of the nomogram instead of the ANN
      will result in 40 additional patients who will be correctly classified between
      benign and cancer.

PMID- 16945478
TI  - A theoretical steady state analysis indicates that induction of Escherichia coli
      glnALG operon can display all-or-none behavior.
AB  - The nitrogen starvation response in Escherichia coli is characterized by the
      enhanced expression of Ntr regulon, comprising hundreds of genes including the
      one coding for nitrogen-assimilating glutamine synthetase (GS) enzyme. The
      biosynthesis and activity of GS is regulated mainly by nitrogen and carbon levels
      in the cell and monitored by three functionally separable interconnected modules.
      Here, we present the steady-state modular analysis of this intricate network made
      up of a GS bicyclic closed-loop cascade, a NRII-NRI two-component system, and an
      autoregulated glnALG operon encoding genes for GS, NRII, and NRI. Our simulation
      results indicate that the transcriptional output of glnALG operon is discrete and
      switch-like, whereas the activation of transcription factor NRI is graded, and
      the inactivation of GS is moderately ultrasensitive to input stimulus glutamine.
      The autoregulation of the NRII-NRI two-component system was found to be essential
      for the all-or-none induction of the glnALG operon. Furthermore, we show that the
      autoregulated two-component system modulates the total active GS by delineating
      the GS activity from its biosynthetic regulation. Our analysis indicates that the
      exclusive relationship between GS activity and its synthesis is brought about by
      the autoregulated two-component system. The modularity of the network endows the
      system to respond differently to nitrogen depending on the carbon status of the
      cell. Through a system-level quantification, we conclude that the discrete switch
      like transcriptional response of the E. coli glnALG operon to nutrient starvation
      prevents the premature initiation of transcription and may represent the
      desperate attempt by the cell to survive in limiting conditions.

PMID- 16945479
TI  - How to describe genes: enlightenment from the quaternary number system.
AB  - As an open problem, computational gene identification has been widely studied,
      and many gene finders (software) become available today. However, little
      attention has been given to the problem of describing the common features of
      known genes in databanks to transform raw data into human understandable
      knowledge. In this paper, we draw attention to the task of describing genes and
      propose a trial implementation by treating DNA sequences as quaternary numbers.
      Under such a treatment, the common features of genes can be represented by a
      "position weight function", the core concept for a number system. In principle,
      the "position weight function" can be any real-valued function. In this paper, by
      approximating the function using trigonometric functions, some characteristic
      parameters indicating single nucleotide periodicities were obtained for the
      bacteria Escherichia coli K12's genome and the eukaryote yeast's genome. As a
      byproduct of this approach, a single-nucleotide-level measure is derived that
      complements codon-based indexes in describing the coding quality and expression
      level of an open reading frame (ORF). The ideas presented here have the potential
      to become a general methodology for biological sequence analysis.

PMID- 16945480
TI  - Molecular co-expression of the c-Met oncogene and hepatocyte growth factor in
      primary colon cancer predicts tumor stage and clinical outcome.
AB  - INTRODUCTION/HYPOTHESIS: Over-expression of the c-Met receptor tyrosine kinase
      has been described in a variety of cancers and implicated in tumor progression.
      Unlike some solid tumors, current evidence indicates that c-Met activation in
      colon cancer is unrelated to gene mutation, is ligand dependent, and occurs via a
      paracrine fashion. We hypothesize that over-expression of the c-Met receptor and
      its ligand, hepatocyte growth factor (HGF) in the tumor microenvironment is
      associated with tumor progression and metastases. METHODS: Primary tumor c-Met
      and HGF mRNA expression was analyzed in 60 colon adenocarcinomas. Receptor and
      ligand expression was analyzed for correlation and association with
      clinicopathologic features and outcome. RESULTS: Compared to adjacent normal
      mucosa, 69% and 48% of tumors showed a greater than 2- and greater than 10-fold
      elevation in c-Met mRNA, respectively. Elevated HGF mRNA was noted in 47% of
      tumors with 19% having a greater than 10-fold increase. Tumor c-Met expression
      was correlated with HGF expression, and a cohort of 33 patients could be defined
      with both low c-Met and HGF expression. Compared with the 27 tumors with either
      high c-Met or HGF, the cohort with low c-Met and HGF expression had fewer nodal
      and distant metastases as well as improved overall survival (HR=2.3, p<0.05).
      CONCLUSION: Evaluation of the c-Met receptor in context of ligand, HGF, allows
      identification of a metastatic phenotype that correlates with advanced stage and
      poor survival. c-Met and HGF co-expression in the tumor microenvironment could be
      useful in the molecular staging of colon cancer and viable therapeutic targets.

PMID- 16945481
TI  - Cystatin C as a potential marker for relapse in patients with non-Hodgkin B-cell
      lymphoma.
AB  - The concentration of cysteine protease inhibitor cystatin C was determined in
      sera from 59 patients with non-Hodgkin B-cell lymphoma using ELISA. The sera from
      43 age and sex matched healthy blood donors served as controls. Cystatin C was
      significantly increased in sera of patients without therapy (mean 1136+/-SE
      105.7ng/ml, p=0.00001) and with therapy (mean 1073+/-52ng/ml, p=0.001) compared
      to controls (mean 819+/-28ng/ml). The highest levels were determined in sera of
      patients with a relapse (mean 1680+/-196ng/ml). By using immunofluorescence
      staining and confocal microscopy we determined immature dendritic cells as a
      major population of cystatin C positive cells in affected lymph nodes. Our study
      reports for the first time that cystatin C is a potential marker for relapse in
      patients with non-Hodgkin B-cell lymphoma.

PMID- 16945482
TI  - Adsorption, desorption and bioregeneration in the treatment of 2-chlorophenol
      with activated carbon.
AB  - This study aims to clarify the effect of activated carbon type on the extent of
      adsorbability, desorbability, and bioregenerability in the treatment of 2
      chlorophenol. Four different activated carbon types; thermally activated and
      chemically activated powdered carbons (PAC), and their granular countertypes
      (GAC) with similar physical characteristics were used. Thermally activated
      carbons adsorbed 2-chlorophenol much better than chemically activated ones.
      However, adsorption was more reversible in the case of chemically activated ones.
      The use of powdered and granular activated carbon countertypes resulted in
      comparable adsorption and desorption characteristics. For each activated carbon
      type, 2-chlorophenol exhibited higher adsorbability and lower desorbability than
      phenol. Biodegradation of 2-chlorophenol took place very slowly when it was used
      as the sole carbon source in acclimated and non-acclimated activated sludges.
      Bioregeneration occurred only via desorption due to an initial concentration
      gradient and no further desorption took place due to low biodegradability.
      Bioregeneration of activated carbon loaded with 2-chlorophenol was not a suitable
      option when 2-chlorophenol was the only carbon source. It is suggested to remove
      2-chlorophenol via adsorption onto activated carbon rather than applying
      biological treatment. Also in such cases, the use of thermally activated carbons
      with higher adsorption and lower desorption capacities is recommended rather than
      chemically activated carbons.

PMID- 16945483
TI  - High loading toluene treatment in a compost based biofilter using up-flow and
      down-flow swing operation.
AB  - A compost/ceramic (1:1, v/v) three section laboratory-scale biofilter inoculated
      with acclimated activated sludge was examined to treat high loading toluene
      vapors from a synthetic gas stream. The biofilter was operated continuously at
      different gas flow rates, 0.108-0.15m(3)h(-1), with inlet toluene concentrations
      ranging 0.5-13gm(-3). The overall performance of the biofilter was divided to
      seven stages according to the mode of operation (down-flow and up-flow) over a
      period of 102 days. Removal efficiencies ranging from 48 to 100% and elimination
      capacities ranging from 26 to 180gm(-3)h(-1) were observed depending on the
      initial loading rates and the mode of operations. A maximum elimination capacity
      of 180gm(-3)h(-1) was observed in the last period at an inlet toluene
      concentration of about 13gm(-3). The results showed that changing the mode of
      operation (up-flow and down-flow) periodically will improve the performance of
      the biofilter under high inlet toluene concentration (higher than 4gm(-3)).
      Results obtained in this study provide insight into the possibility of the
      biofilter to treat high inlet concentrations rather than low concentrations well
      known in the literature.

PMID- 16945484
TI  - Differential contribution of TRPV1 to thermal responses and tissue injury-induced
      sensitization of dorsal horn neurons in laminae I and V in the mouse.
AB  - Our previous recordings from dorsal root ganglion and spinal lamina V neurons
      from TRPV1-mutant mice showed dramatic decreases in responses to temperatures
      near the activation threshold of this channel (43-49 degrees C). Somewhat
      unexpectedly, we only observed behavioral deficits in these mice at higher
      temperatures (50-58 degrees C). In the present study, we tested the hypothesis
      that the noxious heat-evoked pain behavior that persists in TRPV1-mutant mice
      reflects residual responsiveness of neurons in the superficial, but not deep,
      dorsal horn. To this end, we performed in vivo extracellular recordings of spinal
      nociresponsive neurons in laminae I and V in wild type (WT) and TRPV1 mutant
      mice. Neurons in WT and mutant mice from both laminae did not differ in their
      spontaneous activity or evoked responses to mechanical or cold stimuli. By
      contrast, most lamina I neurons from mutant mice responded to noxious heat with
      significantly higher thresholds than in WT mice. In contrast, lamina V neurons
      from mutant mice were virtually unresponsive to noxious heat before and after
      topical mustard oil-induced tissue injury. Interestingly, lamina I neurons in
      mutant mice displayed thermal sensitization following tissue injury, comparable
      in magnitude, but of shorter duration, than in WT mice. We conclude that TRPV1 is
      necessary for noxious heat-evoked responses of lamina V neurons, both before and
      after tissue injury. It is also an essential contributor to the normal activation
      threshold of lamina I neurons to noxious heat and for the full duration of
      thermal sensitization of lamina I neurons following injury. Finally, our results
      suggest that the processing of noxious thermal messages by neurons in lamina I
      involves convergent inputs from a heterogeneous population of primary afferent
      thermal nociceptors.

PMID- 16945485
TI  - Spinal pathways involved in supraspinal modulation of neuropathic manifestations
      in rats.
AB  - Controversial results have been recently reported on the role of supraspinal
      centers in the modulation of nociceptive behavior in animal models of
      mononeuropathy. Our aim was to investigate the role of the various spinal
      pathways in the modulation of the neuropathic manifestations. Several groups of
      rats were subjected to selective spinal-tract lesions, either 2-3 weeks before or
      2-3 weeks after the induction of mononeuropathy following the chronic
      constriction injury (CCI) or the spared nerve injury (SNI) models. Tactile and
      cold allodynias were assessed by Von Frey filaments and the acetone drops test,
      respectively. Thermal hyperalgesia was assessed by the paw withdrawal and the hot
      plate tests. The effects of unilateral and bilateral lesions of the dorso-lateral
      funiculus (DLF), the anterolateral column (ALC) or hemisection were tested over a
      period of 4-8 weeks. All spinal tract lesions produced reversible, but
      significant decrease of allodynia and hyperalgesia over a period of 1-3 weeks.
      The most pronounced effects were observed with bilateral lesions. The stronger
      attenuation was observed on thermal hyperalgesia, assessed by the paw withdrawal
      test, while cold allodynia was the least affected. Spinal lesions performed
      before the induction of neuropathy did not produce significant alterations in the
      temporal development of neuropathic manifestations. The present results allow the
      conclusion that all spinal tracts can be involved in the rostral transmission and
      the descending modulation of neuropathic manifestations. The recovery of symptoms
      following spinal lesions provides illustration on the plasticity of the neural
      network involved in the processing of the neuropathic syndromes.

PMID- 16945486
TI  - Mass spectrometry identification of circulating alpha-1-B glycoprotein, increased
      in aged female C57BL/6 mice.
AB  - In this study, we surveyed the profiles of mouse circulating proteins by 2
      dimensional SDS-PAGE in different strains, sexes and ages. Among visible protein
      spots on 2-D gels with silver-staining, we identified a unique set of 7 seemingly
      related proteins whose levels were consistently elevated in older C57BL/6 female
      mice. This set of 7 proteins was absent in C57BL/6 males or in BALB/c mice of
      either sex of any age. When C57BL/6 female mice were crossed with BALB/c males,
      the age-related increase of these proteins became sporadic and not linear in the
      F1 offspring. All 7 spots of this protein group were picked and subjected to
      identification by mass spectrometric analysis after tryptic digestion. The
      results showed that all 7 spots were different isoforms of alpha(1)B-glycoprotein
      with different degrees of post-translational modifications, such as
      phosphorylation. These results suggest that alpha(1)B-glycoprotein changes in
      mice in a sex and age dependent manner.

PMID- 16945487
TI  - Brief motivational enhancement and coping skills interventions for heavy
      drinking.
AB  - Two brief (3-session) interventions were evaluated in a community sample of 98
      non-dependent heavy drinking adults. Three weeks of intensive daily monitoring of
      drinking using a hand-held computer were completed before and after a 3-week
      intervention phase in which participants were randomly assigned to a brief coping
      skills, brief motivational enhancement, or waiting list condition. Waiting list
      participants drank more before, during, and after the brief intervention than
      brief intervention subjects, but all participants demonstrated reductions in
      drinking amount and frequency. No differences in drinking were found between the
      two brief interventions. The potential value of intensive daily monitoring as a
      tool for non-alcohol dependent individuals interested in reducing their drinking
      was considered.

PMID- 16945488
TI  - Mitochondrial genome of the moon jelly Aurelia aurita (Cnidaria, Scyphozoa): A
      linear DNA molecule encoding a putative DNA-dependent DNA polymerase.
AB  - The 16,937-nuceotide sequence of the linear mitochondrial DNA (mt-DNA) molecule
      of the moon jelly Aurelia aurita (Cnidaria, Scyphozoa) - the first mtDNA sequence
      from the class Scypozoa and the first sequence of a linear mtDNA from Metazoa -
      has been determined. This sequence contains genes for 13 energy pathway proteins,
      small and large subunit rRNAs, and methionine and tryptophan tRNAs. In addition,
      two open reading frames of 324 and 969 base pairs in length have been found. The
      deduced amino-acid sequence of one of them, ORF969, displays extensive sequence
      similarity with the polymerase [but not the exonuclease] domain of family B DNA
      polymerases, and this ORF has been tentatively identified as dnab. This is the
      first report of dnab in animal mtDNA. The genes in A. aurita mtDNA are arranged
      in two clusters with opposite transcriptional polarities; transcription
      proceeding toward the ends of the molecule. The determined sequences at the ends
      of the molecule are nearly identical but inverted and lack any obvious potential
      secondary structures or telomere-like repeat elements. The acquisition of
      mitochondrial genomic data for the second class of Cnidaria allows us to
      reconstruct characteristic features of mitochondrial evolution in this animal
      phylum.

PMID- 16945489
TI  - Penaeus monodon gene discovery project: the generation of an EST collection and
      establishment of a database.
AB  - A large-scale expressed sequence tag (EST) sequencing project was undertaken for
      the purpose of gene discovery in the black tiger shrimp Penaeus monodon.
      Initially, 15 cDNA libraries were constructed from different tissues (eyestalk,
      hepatopancrease, haematopoietic tissue, haemocyte, lymphoid organ, and ovary) of
      shrimp, reared under normal or stress conditions, to identify tissue-specific
      genes and genes responding to infection and heat stress. A total of 10,100 clones
      were analyzed by single-pass sequencing from the 5' end. Clustering and
      assembling of these ESTs resulted in a total of 4845 unique sequences with 917
      overlapping contigs and 3928 singletons. The redundancy of each cDNA library
      ranged from 13.4% to 61.3% with an overall redundancy of 61.1%. About half of
      these ESTs (2365 clones, 48.8%) showed significant homology (BLASTX, e-values
      <10(-4)) to known genes. A high proportion of P. monodon ESTs was most similar to
      the predicted protein sequences from various organisms, e.g. Homo sapiens (9%),
      Mus musculus (7%), Drosophila (6%), Gallus sp.(6%), and Anopheles (5%). Only 6%
      showed the highest similarity to other known genes from shrimp due to the limited
      sequence entries of the species in the public database. Several tissue-specific
      transcripts were identified as well as the candidate genes that may be implicated
      in the immune response. In addition, bioinformatic mining of microsatellites from
      the P. monodon ESTs identified 997 unique microsatellite containing ESTs in which
      74 loci resided within the genes of known functions. Consequently, the P. monodon
      EST database was established. The EST sequence data and the BLAST results were
      stored and made available through a web-accessible database (). This EST database
      provides a useful resource for gene identification and functional genomic studies
      of shrimp.

PMID- 16945490
TI  - Proliferative arrest and activation of apoptosis related genes in Rolly Protein
      silenced cells.
AB  - Here we describe a novel small polypeptide expressed in chick embryo and mouse
      adult tissues referred to as Rolly Protein (Rolp), expressed at the highest
      levels in tibial cartilage and lung respectively. Investigating its putative role
      in cartilage differentiation we found that its expression is restricted to
      proliferative stages consistently with a decreased proliferation rate observed in
      Rolp-silenced cells. Additional functional studies demonstrate that inhibition of
      Rolp expression causes a transcription modulation of genes involved in apoptosis.
      The results here provided strongly suggest an active role of Rolp in the control
      of cell proliferation and apoptosis.

PMID- 16945491
TI  - Women's perception of male erectile dysfunction drugs in the general population.
AB  - OBJECTIVE: The aim of this study is to investigate trends in women's perception
      of male erectile dysfunction (ED) drugs in the general population. METHODS: We
      designed an online questionnaire survey and randomly invited an initial total of
      2370 women to respond to it from a database population that included 450,000 men
      and women recruited through an Internet-based market research company. The 17
      items of the questionnaire comprised 9 items related to socio-cultural background
      and 8 items related to the perception of ED drugs, ED itself, and sexual
      relations. RESULTS: A total of 1262 women (53.2% of those initially invited),
      ranging in age from 20 to 77 years, participated. Among the participants, 83.3%
      were aware of the existence of ED drugs, but only 12.0% showed some interest in
      them, 46.4% and 43.2% of the participants claimed to have an unfavorable image of
      ED drugs, and of men using ED drugs, respectively. Among the participants, 45.2%
      stated that if their partners suffered from ED at present or in the future, they
      would not desire their partners to use ED drugs, and 25.5% stated that they would
      not accept it. Multiple logistic regression analysis revealed that higher age had
      a negative impact on knowledge, interest and image of ED drugs, the image of men
      using ED drugs, and the importance of sexual relations. CONCLUSIONS: Our findings
      reveal that a high proportion of women have a negative perception of ED drugs and
      associated issues in Japan.

PMID- 16945492
TI  - Vitamin A palmitate and aciclovir biodegradable microspheres for intraocular
      sustained release.
AB  - The aim of this study was to obtain a prolonged release of Vitamin A palmitate
      (RAP) and aciclovir from biodegradable microspheres for intraocular
      administration with an antiviral action and to be capable of preventing the
      inherent risks of intravitreal administration. The RAP effect on the microsphere
      characteristics was also studied. Poly(D,L-lactic-co-glycolic) acid microspheres
      were prepared by the solvent evaporation method. Different quantities of
      aciclovir (40-80 mg) and RAP (10-80 mg) were added to the internal phase of the
      emulsion. Microspheres were analysed by scanning electron microscopy, which
      revealed a spherical surface and a porous structure, and granulometric analysis
      that showed an adequate particle size for intraocular administration. The
      aciclovir loading efficiency increased when Vitamin A palmitate was added.
      Differential scanning calorimetry detected no differences in the polymer glass
      transition temperature and the aciclovir melting endotherm in all formulations.
      The release of aciclovir during the first days of the in vitro assay was improved
      with respect to microspheres without RAP. The microspheres showed a constant
      release of aciclovir and RAP for 49 days. Best results were obtained for
      microspheres prepared with 40 mg aciclovir, 80 mg RAP and 400mg polymer. A dose
      of 4.74 mg of microspheres would be therapeutic for the herpes simplex and
      Epstein-Barr viruses' treatment in an animal model and would reduce the
      intravitreal adverse effects. The injectability of a suspension of microspheres
      in isotonic saline solution resulted appropriate for its injection through a 27 G
      needle.

PMID- 16945493
TI  - Mutations of connexin 26 at position 75 and dominant deafness: essential role of
      arginine for the generation of functional gap-junctional channels.
AB  - Gap-junctional channels are large intercellular aqueous pores formed by head-to
      head association of two gap-junctional hemichannels (connexin hexamers), one from
      each of the adjacent cells. The mechano-transduction of sound waves into
      electrical impulses occurs in the cochlea, which houses the organ of Corti.
      Hereditary deafness is frequent and mutations of connexin 26, the predominant
      connexin of the cochlea, are its most frequent cause. Mutations of R75 cause
      deafness and disrupt gap-junctional communication. Here, we determined the
      effects of substitutions of R75 with different residues (alanine, asparagine,
      aspartic acid, lysine, phenylalanine, tyrosine or tryptophan) on formation of gap
      junctional channels and hemichannels. We show that connexin 26 R75 is essential
      for the formation of gap-junctional channels. Substitution of R75 with aromatic
      residues yields functional hemichannels that display altered voltage dependence,
      whereas substitution with other residues yields non-functional hemichannels. The
      expression of R75 mutants has a dominant negative effect on gap-junctional
      communication mediated by wild-type connexin 26, independently of the ability of
      the mutants to form functional gap-junctional hemichannels. Our results show that
      the arginine located at position 75 of connexin 26 is essential for function, and
      cannot be replaced by other residues.

PMID- 16945494
TI  - The S1P2 sphingosine 1-phosphate receptor is essential for auditory and
      vestibular function.
AB  - Sphingosine 1-phosphate (S1P) is an endogenous growth factor with potent effects
      on many different cell types. Most of these effects are produced by activation of
      one or more of a family of G-protein coupled receptors. The S1P2 receptor can
      mediate S1P-induced proliferation, differentiation and survival in a wide variety
      of cells in culture. However, identifying essential in vivo functions for S1P2
      has been hampered by its ubiquitous expression and the failure to detect any
      anatomical abnormalities in initial analyses of S1P2 knockout mice. We report
      here that all S1P2 knockout mice are profoundly deaf from postnatal day 22 and
      approximately half display a progressive loss of vestibular function with aging.
      Anatomically, both the auditory and vestibular systems appear to develop normally
      but then degrade. Morphological defects associated with hearing are first
      detected at 3 weeks postnatal as deformations of the organ of Corti/Nuel's space.
      By one year of age structures within the scala media are dramatically altered.
      The S1P2 knockout mice also display a loss of otoconia consistent with the
      vestibular impairment. The present data are the first to indicate that S1P
      signaling plays critical roles, in vivo, in auditory and vestibular functions.
      The data further establish that the S1P signaling occurs through the S1P2
      receptor and makes an essential contribution to the structural maintenance of
      these systems, raising the possibility that properly targeted enhancement of this
      signaling may prove to be clinically beneficial.

PMID- 16945495
TI  - Responses of inferior colliculus neurons to SAM tones located in inhibitory
      response areas.
AB  - In order to examine the effect of inhibition on processing auditory temporal
      information, responses of single neurons in the inferior colliculus of the
      chinchilla to sinusoidally amplitude-modulated (SAM) tones alone and the presence
      of a steady-state tone were obtained. The carrier frequency of the SAM tone was
      either the characteristic frequency (CF) or a frequency in the inhibitory
      response area of a studied neuron. When the carrier frequency was set to the
      neuron's CF, neurons responded in synchrony to the SAM-tone envelope, as
      expected. When the carrier frequency was set to a frequency at which pure tones
      produced inhibition, SAM tones elicited little or no response, also as expected.
      However, when the same SAM tone was paired with a pure tone whose frequency was
      set to the neuron's CF, responses synchronized to the SAM tone envelope were
      obtained. These modulated responses were typically one-half cycle out-of-phase
      with the response to the SAM tone at CF, suggesting that they arose from cyclic
      inhibition and release from inhibition by the SAM tone. The results demonstrate
      that the representation of temporal information by inferior colliculus neurons is
      influenced by temporally-patterned inhibition arising from locations remote from
      CF.

PMID- 16945496
TI  - Low coherence interferometry of the cochlear partition.
AB  - Interferometric measurement of the vibration of the organ of Corti in the
      isolated guinea pig cochlea was conducted using low-coherence light (1310+/-47 nm
      wavelength) from a superluminescent diode. The short coherence length of the
      light source localized measurements along the axial direction to within a
      approximately 10-microm window (in tissue), even when using a low numerical
      aperture lens. The ability to accomplish this is important because measurement of
      the vibration of the basal-turn organ of Corti is generally done via a small hole
      in the bone of the cochlea, which effectively limits the numerical aperture. The
      axial localization, combined with the inherent sensitivity of the method, allowed
      distinct measurements of the basilar membrane (BM) and the putative reticular
      lamina (RL) vibration using only the native tissue reflectance, that is without
      requiring the use of reflective particles. The system was first operated in a
      scanning mode as an optical coherence tomography (OCT) system to yield an image
      of the organ of Corti. The reflectance of intensity from the BM and RL was 8x10(
      5) and 8x10(-6), respectively. The internal structure between the BM and RL
      presented a variable reflectivity of about 10(-7). A mirror would define a
      reflectance of 1.00. Then the instrument was operated as a homodyne
      interferometer to measure the displacement of either the BM or RL. Vibration at
      16 kHz was induced by a piezoelectric actuator, causing whole movement of a
      dissected cochlea. After calibration of the system, we demonstrated clear
      measurement of mechanically driven vibration for both the BM and RL of 0.30 nm
      above a noise floor equivalent to 0.03 nm. OCT interferometry, when adapted for
      in vivo organ of Corti measurements, appears suitable to determine the
      micromechanical vibration of cells and tissue elements of the organ.

PMID- 16945497
TI  - Long-lived C. elegans mitochondrial mutants as a model for human mitochondrial
      associated diseases.
AB  - Mitochondria play a pivotal role in the life of cells, controlling diverse
      processes ranging from energy production to the regulation of cell death. In
      humans, numerous pathological conditions have been linked to mitochondrial
      dysfunction. Cancer, diabetes, obesity, neurodegeneration, cardiomyopathy and
      even aging are all associated with mitochondrial dysfunction. Over 400 mutations
      in mitochondrial DNA result directly in pathology and many more disorders
      associated with mitochondrial dysfunction arise from mutations in nuclear DNA. It
      is counter-intuitive then, that a class of mitochondrially defective mutants in
      the nematode Caenorhabditis elegans, the so called Mit (Mitochondrial) mutants,
      in fact live longer than wild-type animals. In this review, we will reconcile
      this paradox and provide support for the idea that the Mit mutants are in fact an
      excellent model for studying human mitochondrial associated diseases (HMADs). In
      the context of the 'Mitochondrial Threshold Effect Theory', we propose that the
      kinds of processes induced to counteract mitochondrial mutations in the Mit
      mutants (and which mediate their life extension), are very likely the same ones
      activated in many HMADs to delay disease appearance. The identification of such
      compensatory pathways opens a window of possibility for future preventative
      therapies for many HMADs. They may also provide a way of potentially extending
      human life span.

PMID- 16945498
TI  - Exploring the black box of a decision aid: what information do patients select
      from an interactive Cd-Rom on treatment options in breast cancer?
AB  - OBJECTIVE: It is thought that patients fare better when they participate in
      treatment decision-making, and when they have more control over the amount and
      type of information they receive. To facilitate informed decision-making,
      interactive decision aids have been introduced in health care. This article
      describes how much, and which information patients select from an interactive
      decision aid on breast cancer. To explore whether the interactive system
      facilitates that different patients receive different information, associations
      between patients' characteristics and information selection are inspected.
      METHODS: The interactive decision aid was provided to 106 patients after an
      initial discussion with their surgeon about their diagnosis and treatment
      options. Information regarding patients' age, completed education, treatment
      preference, psychological functioning, decision uncertainty and decision style
      was collected with a written, structured questionnaire. The questionnaire was
      completed before patients used the interactive decision aid. To create
      categories, a median-split procedure was employed on the scores of the continuous
      background variables. The information patients selected from the interactive
      decision aid were registered into logfiles. Associations between patients'
      background variables and information selection were investigated by means of
      univariate statistics. RESULTS: Patients (n=97; 92%) used the interactive
      decision aid intensively. On average, patients spent almost 70min searching for
      information and selected 21 information topics. Overall, treatment related
      information was clearly more selected than other types of information. Age,
      education, and decision style factors were associated with information selection.
      CONCLUSION: The interactive breast cancer decision aid was utilized intensively.
      The interactive system was found to facilitate that different patients received
      different amounts and types of information. PRACTICE IMPLICATIONS: Interactive
      decision aids may improve information giving to patients, and as a result, the
      quality of care. To safeguard informed-choice, decision aids should be used in
      conjunction with other communication strategies. Decision aids should be
      available continuously and throughout the patients' disease journey. The Internet
      may help to achieve broad dissemination and enduring access.

PMID- 16945499
TI  - Reduced recanalization rates of the great saphenous vein after endovenous laser
      treatment with increased energy dosing: definition of a threshold for the
      endovenous fluence equivalent.
AB  - BACKGROUND: Recent reports indicated a correlation between the amount of energy
      released during endovenous laser treatment (ELT) of the great saphenous vein
      (GSV) and the success and durability of the procedure. Our objective was to
      analyze the influence of increased energy dosing on immediate occlusion and
      recanalization rates after ELT of the GSV. METHODS: GSVs were treated with either
      15 or 30 W of laser power by using a 940-nm diode laser with continuous fiber
      pullback and tumescent local anesthesia. Patients were followed up prospectively
      with duplex ultrasonography at day 1 and at 1, 3, 6, and 12 months. RESULTS: A
      total of 114 GSVs were treated with 15 W, and 149 GSVs were treated with 30 W.
      The average endovenous fluence equivalents were 12.8 +/- 5.1 J/cm2 and 35.1 +/-
      15.6 J/cm2, respectively. GSV occlusion rates according to the method of Kaplan
      and Meier for the 15- and 30-W groups were 95.6% and 100%, respectively, at day
      1, 90.4% and 100% at 3 months, and 82.7% and 97.0% at 12 months after ELT (log
      rank; P = .001). An endovenous fluence equivalent exceeding 20 J/cm2 was
      associated with durable GSV occlusion after 12 months' follow-up, thus suggesting
      a schedule for dosing of laser energy with respect to the vein diameter.
      CONCLUSIONS: Higher dosing of laser energy shows a 100% immediate success rate
      and a significantly reduced recanalization rate during 12 months' follow-up.

PMID- 16945500
TI  - Prognostic role of factor XIII gene variants in nonhealing venous leg ulcers.
AB  - OBJECTIVE: Many factors impair healing of chronic venous ulcer (CVU), and many
      theories have been proposed to explain their pathogenesis. Coagulation factor
      XIII (FXIII) influences tissue regeneration and angiogenesis with effects on
      wound healing. Because FXIII properties depend upon its genetic variants, we
      investigated whether intragene polymorphisms may have modulating effects on the
      CVU area. METHODS: The study included 121 patients with nonhealing CVUs (CEAP
      clinical class C6) that included 67% with primary chronic venous disease (CVD),
      26% with post-thrombotic ulcers, and 7% with mixed ulcer origin. Polymerase chain
      reaction was used to genotype them for Val34Leu, Pro564Leu, and Tyr204Phe
      variants in the FXIII-A subunit gene and for His95Arg variant in the FXIII-B
      subunit gene. The same variants were analyzed in 102 controls, healthy subjects
      who were case-matched by age and gender. RESULTS: Genotype distribution for all
      polymorphisms investigated was not significantly different between cases and
      controls. Conversely, our CVU cases had a mean ulcer area inversely related with
      the presence of both Leu34 and Leu564 alleles (ValVal, 12.3 +/- 22.4 cm2 vs
      LeuLeu, 3.9 +/- 2.6 cm2, P = .002; ProPro, 10.2 +/- 21.2 cm2 vs LeuLeu, 2.9 +/-
      1.4 cm2, P = .002). In combined analysis, those cases who were wild-type for both
      variants (ValVal34/ProPro564) had a further increase in mean ulcer size compared
      with cases carrying both variants (Leu34/Leu564) (13.3 +/- 27.1 cm2 vs 5.2 +/-
      5.6 cm2; P = .034). CONCLUSIONS: No correlation exists between FXIII genotypes
      and the prevalence of chronic venous ulcers, thus demonstrating that FXIII
      polymorphisms have no role in ulcer development. In contrast, FXIII-gene
      variants, in particular the non-wild-type alleles Leu34 and Leu564, were
      associated with a smaller venous ulcer surface and might have favorable effects
      on reparative processes.

PMID- 16945501
TI  - Spontaneous appearance of uterine tumors in vehicle and 3-methylcholanthrene
      treated Wistar rats.
AB  - During the conduct of a study designed to determine the effect of 3
      methylcholanthrene (3-MC), a synthetic polycyclic aromatic hydrocarbon (PAH) that
      acts through the aryl hydrocarbon receptor (AhR), on uterine contractility in
      Wistar rats, uterine tumors were identified in both vehicle and 3-MC-treated
      animals. The objective of the current study was to describe the histological
      characteristics of these tumors. Sexually mature female rats (110 days old) were
      treated with 70 micro mol/kg 3-MC or vehicle (olive oil) for 4 days and
      euthanized by exsanguination. At necropsy uterine tumors were unexpected findings
      in two vehicle and four 3-MC-treated rats. The tumors appeared as multiple
      unilateral or bilateral subserosal nodes. No tumors were found in other tissues
      on gross inspection. Prior to necropsy, tumor-presenting animals were acyclic and
      arrested in a state of persistent proestrus. Haematoxylin and eosin staining of
      tumor sections revealed nests of acidophilic granule-containing cells within a
      highly vascular stroma of the uterine wall below the muscularis. Positive
      periodic acid Schiff (PAS) staining suggested the presence of glycogen or
      glycophospholipids within these granules, however, negative PAS diastase staining
      indicated that the acidophilic bodies were not composed of glycogen. The tumors
      are histologically similar to human dysgerminomas. We conclude that these tumors
      are unrelated to treatment and are of a granular type not previously documented
      in Wistar rats.

PMID- 16945502
TI  - Hold your horses: a dynamic computational role for the subthalamic nucleus in
      decision making.
AB  - The basal ganglia (BG) coordinate decision making processes by facilitating
      adaptive frontal motor commands while suppressing others. In previous work,
      neural network simulations accounted for response selection deficits associated
      with BG dopamine depletion in Parkinson's disease. Novel predictions from this
      model have been subsequently confirmed in Parkinson patients and in healthy
      participants under pharmacological challenge. Nevertheless, one clear limitation
      of that model is in its omission of the subthalamic nucleus (STN), a key BG
      structure that participates in both motor and cognitive processes. The present
      model incorporates the STN and shows that by modulating when a response is
      executed, the STN reduces premature responding and therefore has substantial
      effects on which response is ultimately selected, particularly when there are
      multiple competing responses. Increased cortical response conflict leads to
      dynamic adjustments in response thresholds via cortico-subthalamic-pallidal
      pathways. The model accurately captures the dynamics of activity in various BG
      areas during response selection. Simulated dopamine depletion results in emergent
      oscillatory activity in BG structures, which has been linked with Parkinson's
      tremor. Finally, the model accounts for the beneficial effects of STN lesions on
      these oscillations, but suggests that this benefit may come at the expense of
      impaired decision making.

PMID- 16945503
TI  - RAFTK/Pyk2 regulates EGF-induced PC12 cell spreading and movement.
AB  - The protein tyrosine kinase RAFTK, also termed Pyk2, is a member of the focal
      adhesion kinase (FAK) subfamily. In this report, we show the role of RAFTK in
      neuroendocrine PC12 cells upon epidermal growth factor (EGF) stimulation.
      Following EGF treatment, we observed that RAFTK was tyrosine-phosphorylated in a
      time- and dose-dependent manner, while FAK was constitutively phosphorylated and
      primarily regulated by cell adhesion. Moreover, we found that RAFTK associated
      with the phosphorylated EGF receptor (EGFR) upon EGF stimulation. RAFTK
      phosphorylation was mediated primarily through PLCgamma-IP3-Ca(2+) signaling and
      partially through PI3-Kinase. Furthermore, overexpression of PRNK, a specific
      dominant-negative construct of RAFTK, was sufficient to block EGF-induced cell
      spreading and movement. Paxillin, a key modulator of the actin cytoskeleton and
      an RAFTK substrate, was also phosphorylated following EGF treatment. EGF induced
      a dynamic reorganization of RAFTK and paxillin at neuronal adhesion sites, with
      the specific localization of paxillin at the inner juxtaposition of RAFTK.
      Additionally, we observed that RAFTK associated with the scaffold protein c-Cbl
      and mediated its phosphorylation. Our data demonstrate that while FAK mediated
      cell adhesion, RAFTK was localized at the cytoplasm where it mediated inside-out
      signaling through intracellular Ca(2+), thus leading to cell spreading and
      movement upon EGF stimulation.

PMID- 16945504
TI  - The combination of topiramate and diazepam is partially neuroprotective in the
      hippocampus but not antiepileptogenic in the lithium-pilocarpine model of
      temporal lobe epilepsy.
AB  - Lithium-pilocarpine induces status epilepticus (SE), leading to extensive damage
      and spontaneous recurrent seizures (SRS). Neuroprotective and antiepileptogenic
      effects of topiramate (TPM) associated with diazepam (DZP) were investigated in
      this model. SE was induced by LiCl and pilocarpine. TPM (10, 30 or 60 mg/kg) was
      injected at the onset of SE and 10h later and DZP (2.5 and 1.25mg/kg) at 2 and
      10h after SE. TPM treatment was continued twice daily for 6 days. Other rats
      received two injections of DZP on the day of SE. Cell counting was performed on
      thionine-stained sections 14 days after SE and after 2 months of epilepsy.
      Occurrence and frequency of SRS were video-recorded. The MRI T2-weighted signal
      was quantified in hippocampus and ventral cortices. DZP-TPM treatment induced
      partial neuroprotection in CA1 and hilus, and tended to increase the percentage
      of rats with protected neurons in layer III/IV of the ventral entorhinal cortex.
      The latency to and frequency of SRS were not modified by DZP-TPM. T2-weighted
      signal was decreased in hippocampus 3 days after SE at all TPM doses and in
      ventral hippocampus after epilepsy onset. In conclusion, although DZP-TPM
      treatment was able to partially protect two areas critical for epileptogenesis,
      the hippocampus and ventral entorhinal cortex, it was not sufficient to prevent
      epileptogenesis.

PMID- 16945506
TI  - Procedural learning in schizophrenia investigated with functional magnetic
      resonance imaging.
AB  - A cerebral basis for the acquisition and retention of procedural knowledge in
      schizophrenia was examined with 1.5 T functional MRI during an embedded sequence
      Serial Reaction Time Task (SRTT) in 10 chronic medicated patients and 15 healthy
      controls. Comparable procedural learning was observed in both groups, suggesting
      that the impairment reported in previous schizophrenia samples may not be robust.
      Consistent with previous fMRI reports, procedural learning in the control group
      was associated with activity in the dorsal striatum, anterior cingulate, parietal
      cortex and frontal cortex. Greater procedural learning related activity was
      observed in the control relative to the schizophrenia group in the bilateral
      frontal, left parietal and bilateral caudate regions. Patients did not activate
      frontal or parietal areas while responding to the embedded sequence within the
      SRTT, but greater activation during procedural learning was observed relative to
      the control sample in the right anterior cingulate, left globus pallidus and the
      right superior temporal gyrus. Thus, despite comparable instantiation of
      procedural learning in schizophrenia, the cerebral activation associated with
      this cognitive skill was abnormal. The paucity of activity in bilateral frontal
      cortex, left parietal cortex and bilateral caudate nucleus may represent cerebral
      dysfunction associated with schizophrenia, whereas the hyperactivation of the
      right superior temporal gyrus, the right anterior cingulate cortex and the left
      globus pallidus may represent a compensatory cerebral action capable of
      facilitating near-normal task performance. The results are thus consistent with a
      neurodevelopmental pathology impinging on fronto-subcortical circuitry.

PMID- 16945505
TI  - Delusions and processing of discrepant information: an event-related brain
      potential study.
AB  - One possible explanation for why delusions persist despite the awareness of
      contradictory information is that the new information fails to be integrated.
      Interestingly, the amplitude of the N400 event-related brain potential (ERP) has
      been proposed as an index of the integration of information that is discrepant
      with expectancies whatever the task in which the potential is found. Thus,
      delusions may persist because of a deficit in integration as indexed by the N400.
      To test this hypothesis, ERPs were recorded in 35 schizophrenia patients (mean
      age=30.5+/-5.6 years) and 26 normal controls during a task in which they either
      had to decide whether or not each target word could be integrated into the
      category "animal", or had no decision to make, according to the prompt "animal?"
      or the prompt "inaction". In these conditions, the amplitudes of the N400s to
      target words that were discrepant with the category were found to be negatively
      correlated with delusion severity. The patient group was then dichotomized
      according to a median split of delusion severity, excluding the 5 patients with
      delusion scores at the median. Mean age, sex ratio, and severity of conceptual
      disorganization and hallucinations of the two subgroups differed. Controlling for
      these 4 covariates, the N400s for discrepant targets were found smaller in the 14
      More-Delusional patients than in the 16 Less-Delusional patients. These results
      support the hypothesis that delusions are associated with smaller N400s in
      patients. Further studies should thus be done to test whether a deficit of N400
      processes could have a causal role in the persistence of delusions.

PMID- 16945507
TI  - Striatal D(2) receptor occupancy in bipolar patients treated with olanzapine.
AB  - We explored the relationship between striatal dopamine-2 (D(2)) receptor
      occupancy and extra-pyramidal symptoms (EPS) in bipolar patients receiving
      olanzapine. Seventeen patients with a DSM-IV diagnosis of bipolar disorder were
      treated with 5-45 mg/day olanzapine for at least 14 days. After that period, D(2)
      receptor occupancy was determined using Iodobenzamide (IBZM) and SPECT. EPS were
      assessed by the Simpson-Angus Scale (SAS) and Barnes-Akathisia Scale (BAS). We
      found a dose-dependent increase in occupancy: 5 mg led to 28-50%, 10 mg to 40
      68%, 15 mg to 69%, 20 mg to 57-66%, 30 mg to 66% and 45 mg to 80% D(2) receptor
      occupancy; and a significant correlation between plasma levels and occupancy
      (R(2)=.55, P=.001). Similar to schizophrenic patients, bipolar patients did not
      exhibit EPS at D(2) occupancy levels of 28 to 80%. Although we did not find an
      increased vulnerability for acute EPS in bipolar patients receiving olanzapine at
      clinical relevant doses, this needs to be replicated with larger sample sizes.

PMID- 16945508
TI  - Visualization of the Xenopus primordial germ cells using a green fluorescent
      protein controlled by cis elements of the 3' untranslated region of the DEADSouth
      gene.
AB  - We succeeded in visualization of the primordial germ cells (PGCs) in a living
      Xenopus embryo. The mRNA of the reporter Venus protein, fused to the 3'
      untranslated region (UTR) of DEADSouth, which is a component of the germ plasm in
      Xenopus eggs, was microinjected into the vegetal pole of fertilized eggs and then
      the cells with Venus fluorescence were monitored during development. The behavior
      of the cells was identical to that previously described for PGCs. Almost all
      Venus-expressing cells were Xdazl-positive in the stage 48 tadpoles, indicating
      that they were PGCs. In addition, we found three sub-regions (A, B and C) in the
      3' UTR, which were involved in the PGC-specific expression of the reporter
      protein. Sub-region A, which was identified previously as a localization signal
      for the germ plasm during oogenesis, participated in anchoring of the mRNA at the
      germ plasm and the degradation of the mRNA in the somatic cells. Sub-regions B
      and C were also involved in anchoring of the mRNA at the germ plasm. Sub-region B
      participated in the enhancement of translation.

PMID- 16945509
TI  - Abnormal brain size effect on the thalamus in autism.
AB  - This study was conducted to examine the volume of the thalamus in autism and to
      investigate the effect of brain size on this structure in an attempt to
      replicate, in a larger sample, findings from a previous study reporting the
      existence of a relationship between brain volume and thalamus in healthy controls
      but not in individuals with autism. Additionally, the relationships between
      thalamic volumes and clinical features were examined. Volumetric measurements of
      the right and left thalamic nuclei were performed on MRI scans obtained from 40
      high-functioning individuals with autism (age range: 8-45 years) and 41 healthy
      controls (age range: 9-43 years). No differences were observed between the two
      groups for unadjusted thalamic volumes. However, the expected linear relationship
      between TBV and thalamic volume was not observed in individuals with autism.
      Furthermore, no correlations were observed between thalamic volumes and clinical
      features. Findings from this larger study are consistent with the previous report
      of an abnormal brain size effect on the thalamus in autism and support the
      possibility of abnormal connections between cortical and subcortical structures
      in this disorder.

PMID- 16945510
TI  - Effects of low-molecular-weight organic ligands and phosphate on DNA adsorption
      by soil colloids and minerals.
AB  - Adsorption of DNA on montmorillonite, kaolinite, goethite and soil clays from an
      Alfisol in the presence of citrate, tartrate and phosphate was studied. A marked
      decrease in DNA adsorption was observed on montmorillonite and kaolinite with
      increasing anion concentrations from 0 to 5 mM. However, the amount of DNA
      adsorbed by montmorillonite and kaolinite was enhanced when ligand concentration
      was higher than 5 mM. In the system of soil colloids and goethite, with the
      increase of anion concentrations, a steady decrease was found and the ability of
      ligands in depressing DNA adsorption followed the sequence: phosphate > citrate >
      tartrate. Compared to H2O2-treated clays (inorganic clays), a sharp decrease in
      DNA adsorption was observed on goethite and organo-mineral complexes (organic
      clays) with increasing ligand concentrations. The results suggest that the
      influence of anions on DNA adsorption varies with the type and concentration of
      anion as well as the surface properties of soil components. Introduction of DNA
      into the system before the addition of ligands had the greatest amount of DNA
      adsorption on soil colloids and goethite. Organic and inorganic ligands promoted
      DNA adsorption on montmorillonite and kaolinite when ligands were introduced into
      the system before the addition of DNA. The results obtained in this study have
      important implications for the understanding of the persistence and fate of DNA
      in soil environments especially rhizosphere soil where various organic and
      inorganic ligands are active.

PMID- 16945511
TI  - Adsorption of copper and zinc on Pseudomonas putida CZ1: particle concentration
      effect and adsorption reversibility.
AB  - The adsorption and desorption processes of Cu(II) and Zn(II) on the biomass of
      Pseudomonas putida CZ1 as a function of particle concentrations (C(p)) were
      studied. In a 0.01 M KNO3 solution, the Cu-biomass and Zn-biomass adsorption
      systems displayed a clear C(p) effect. The overall adsorption isotherms under
      three C(p) conditions could be described as a Freundlich-type C(p) effect
      isotherm equation: gamma = 2.553C(p)(-0.7106) C(eq)(0.8971) for Cu-biomass
      system, gamma = 2.412C(p)(-0.8305) C(eq)(0.6504) for Zn-biomass system. The
      results of experiments, designed to eliminate several typical sources of
      experimental artifact, agree with the prediction of the metastable-equilibrium
      adsorption theory. Results from laboratory equilibration studies also indicate
      that biomass-adsorbed Cu(II) or Zn(II) fractions may be comprised of both
      reversibly and strongly bound or resistant components. A computational method has
      been derived to allow prediction of the magnitude of the reversible and more
      strongly adsorbed Cu(II) or Zn(II) fractions from conventional isotherm data.
      This methodology provides an initial quantitative approximation of the strongly
      bound, resistant, biomass fractions while utilizing relatively simple
      experimental adsorption-desorption data.

PMID- 16945512
TI  - Natural hybridization in primates: one evolutionary mechanism.
AB  - The role and importance of natural hybridization in the evolutionary histories of
      animal taxa is still debated. This results largely from a history of zoological
      investigations that assumed, rather than documented, a limited evolutionary role
      for this process. However, it is now becoming apparent that, just as for plants,
      the creative effects of reticulate evolution are widespread in animal taxa as
      well. This conclusion is supported by the documentation of numerous instances of
      the formation of new taxa and the genetic enrichment through introgressive
      hybridization. In the present review, we use primates as a paradigm for how
      natural hybridization can affect the evolution of species complexes and remains a
      footprint on genomes. Findings for a number of groups, including basal (e.g.
      lemurs) and derived (e.g. Old World apes) lineages, demonstrate that
      introgression and hybrid speciation have caused a reticulate pattern that is
      still detectable in the, often mosaic, genomes of primates. For example, results
      from genetic analyses of our own species demonstrate the process of past
      introgressive hybridization with the progenitors of our sister taxa (i.e.
      chimpanzees and gorillas) and most likely also our extinct, close relatives in
      the hominid lineage.

PMID- 16945513
TI  - Effects of covalently attached chondroitin sulfate on aggrecan cleavage by ADAMTS
      4 and MMP-13.
AB  - Aggrecan is degraded by several aggrecanase-1 (ADAMTS-4) isoforms differing in
      the number of sulfated glycosaminoglycan (sGAG)-binding motifs. ADAMTS-4 and MMPs
      cleave aggrecan more efficiently within the chondroitin sulfate (CS)-rich region
      than the interglobular domain (IGD). We investigated the influence of CS on
      aggrecan core protein cleavage by ADAMTS-4 (p68) and (p40) as well as MMP-13,
      which has no recognizable GAG-binding sites. Chondroitinase ABC-treated cartilage
      aggrecan was cleaved with ADAMTS-4 (p68) less efficiently than CS-substituted
      aggrecan within the CS-2 domain. Keratanase-treated aggrecan exhibited reduced
      IGD cleavage, but when both CS and KS were removed, the IGD cleavage was
      restored. This result suggests that KS in the IGD may compete with CS for ADAMTS
      4 (p68) binding. In the absence of KS, however, p68 binding was shifted to the CS
      2 domain. CS-deficient full-length recombinant aggrecan (rbAgg) was produced by
      chondroitinase ABC treatment, or by expression in the xylosyltransferase
      deficient CHO-pgsA745 cell line. When digested with the ADAMTS-4 (p68), each of
      these preparations exhibited reduced CS-2 domain cleavage compared to CS
      substituted CHO-K1 cell-derived aggrecan. Additionally, CS-deficient rbAgg showed
      increased IGD scission prior to cleavage within the CS-2 domain. ADAMTS-4 (p40)
      readily cleaved both rbAggs within the IGD, but cleaved poorly within the CS-2
      domain, indicating little CS dependence. MMP-13, in contrast, cleaved the CS
      region and the IGD of both CS-substituted and CS-deficient rbAgg equally well.
      These data indicate that covalently bound CS enhances ADAMTS-4-mediated cleavage
      within the CS-rich region. MMP-13 also cleaves preferentially within the CS
      region, but by an apparently CS-independent mechanism.

PMID- 16945514
TI  - A randomised trial comparing 5 mL/kg and 10 mL/kg of pentastarch as a volume
      preload before spinal anaesthesia for elective caesarean section.
AB  - BACKGROUND: Colloid solutions are more effective at preventing hypotension than
      crystalloids when used as a volume preload before caesarean delivery under spinal
      anaesthesia. The ideal volume to infuse has not been established. METHOD: In a
      randomised double-blind trial 70 women presenting for elective caesarean section
      received either 5 mL/kg of pentastarch (group A) or 10 mL/kg of pentastarch
      (group B) as a volume preload before spinal anaesthesia. Hypotension was defined
      as a systolic pressure below 90 mmHg or a decrease of 30% from a baseline value.
      Treatment was with 6-mg increments of ephedrine until resolution. RESULTS: In
      group B, 7/35 patients (20%) developed hypotension, significantly fewer than the
      15/35 (42.8%) in group A (P<0.05). The patients in group B also required less
      ephedrine (total in group, 114 mg) than those in group A (total in group, 198 mg)
      CONCLUSIONS: Pentastarch, 10 mL/kg is more effective than 5 mL/kg at preventing
      hypotension following spinal anaesthesia for caesarean delivery.

PMID- 16945515
TI  - Effect of blood pressure instrument and cuff side on blood pressure reading in
      pregnant women in the lateral recumbent position.
AB  - BACKGROUND: Hydrostatic forces affect non-invasive blood pressure measurement in
      the lateral position. This study assessed the extent of this effect with the
      mercury column sphygmomanometer and Dinamap oscillometric instrument as well as
      different recommendations for comparing supine and lateral blood pressure
      measurements. METHOD: Thirty-two term pregnant women were studied in the
      antenatal clinic. Blood pressure was recorded from both arms in the right lateral
      and supine recumbent positions, using the sphygmomanometer and Dinamap. RESULTS:
      Blood pressure in the uppermost arm while lateral was lower than supine by a mean
      10 mmHg or more. Systolic, mean and diastolic pressures in the dependent arm
      while lateral were higher than supine by a mean (SD) 3.1 (6.8)mmHg, 5.6
      (6.8)mmHg, and 6.9 (8.7)mmHg using the sphygmomanometer and 3.8 (8.1)mmHg, 3.2
      (7.1)mmHg, and 1.9 (5.3)mmHg using the Dinamap. Systolic, mean and diastolic
      pressure values calculated as the average taken from both arms in the lateral
      position were lower than supine by a mean (SD) 3.5 (7.5)mmHg, 3.9 (4.7) mmHg, and
      4.1 (5.8)mmHg using the sphygmomanometer and 4.6 (6.0)mmHg, 4.9 (4.4)mmHg, and
      4.8 (4.4)mmHg using the Dinamap. Corresponding blood pressure readings were
      always higher using the Dinamap than the sphygmomanometer. CONCLUSIONS: In
      normotensive non-labouring term pregnant women, the use of the dependent arm or
      an average blood pressure from both arms while in the lateral position will give
      a closer reading to supine blood pressure than the use of the uppermost arm.
      However, use of the dependent arm is simpler.

PMID- 16945516
TI  - The ProSeal laryngeal mask airway in two failed obstetric tracheal intubation
      scenarios.

PMID- 16945517
TI  - Aspergillus meningitis following spinal anaesthesia for caesarean section in
      Colombo, Sri Lanka.
AB  - We report six cases of Aspergillus meningitis after spinal anaesthesia for
      caesarean section administered in June and July 2005. Three patients died before
      a fungal infection was confirmed at the first post-mortem examination in August.
      Thereafter anti-fungal therapy was successful in saving the lives of the other
      three patients. Some syringes and spinal needles supplied to the hospitals
      concerned were found to be contaminated with Aspergillus fumigatus. Investigators
      found that medical supply storage facilities were substandard following the
      influx of donations after the tsunami of December 2004.

PMID- 16945518
TI  - Reversible posterior leucoencephalopathy syndrome in a peripartum patient.
AB  - We present the case of a multiparous parturient who developed hypertension
      associated with a severe headache in the immediate post-partum period. She
      subsequently suffered a generalised tonic clonic seizure on the fifth post-partum
      day. Following recovery of consciousness, she developed a left homonymous
      hemianopia. Apart from hypertension, headache and convulsion, she had no symptoms
      and no proteinuria or other biochemical or haematological changes associated with
      eclampsia. The magnetic resonance imaging findings were consistent with vasogenic
      oedema in the right posterior parieto-occipital white matter and these in turn
      are consistent with reversible posterior leucoencephalopathy syndrome. The
      differential diagnosis of convulsions in the post-partum period is discussed and
      the clinical and radiological features of reversible posterior
      leucoencephalopathy syndrome are described.

PMID- 16945519
TI  - Failure of an emergency oxygen bypass in an anaesthetic machine due to sunburn!

PMID- 16945520
TI  - Glial regulation of the axonal membrane at nodes of Ranvier.
AB  - Action potential conduction in myelinated nerve fibers depends on a polarized
      axonal membrane. Voltage-gated Na(+) and K(+) channels are clustered at nodes of
      Ranvier and mediate the transmembrane currents necessary for rapid saltatory
      conduction. Paranodal junctions flank nodes and function as attachment sites for
      myelin and as paracellular and membrane protein diffusion barriers. Common
      molecular mechanisms, directed by myelinating glia, are used to establish these
      axonal membrane domains. Initially, heterophilic interactions between glial and
      axonal cell adhesion molecules define the locations where nodes or paranodes
      form. Subsequently, within each domain, axonal cell adhesion molecules are
      stabilized and retained through interactions with cytoskeletal and scaffolding
      proteins, including ankyrins and spectrins.

PMID- 16945521
TI  - Are men with low selenium levels at increased risk of prostate cancer?
AB  - A meta-analysis was undertaken to quantitatively determine if men with low
      selenium levels were at increased risk of prostate cancer. PubMed, EMBASE and
      current contents were searched to identify relevant studies. The effect size was
      calculated by pooling the mean difference for serum, plasma and toenail selenium
      levels (95% confidence intervals) separately and combined using a random effects
      model. Meta-regression analysis explored possible sources of heterogeneity.
      Twenty epidemiologic studies were selected. Mean differences were: -5.55 microg/l
      (-9.82; -1.27; p=0.01), -0.01 microg/g (-0.03; 0.006; p=0.19), -0.52 microg/l (
      4.63; 3.58; p=0.80) for serum, toenail and plasma studies, respectively. Overall,
      the pooled standardized mean difference between cases and controls was; -0.23 (
      0.40; -0.05; p=0.01) indicating a possible inverse association between selenium
      levels and risk of prostate cancer. Differences in selenium levels between
      populations, a possible threshold effect and the relationship between selenium
      and the different stages of prostate cancer require further investigation.

PMID- 16945522
TI  - Autoimmune diseases, asthma and risk of haematological malignancies: a nationwide
      case-control study in Sweden.
AB  - To investigate potential associations between several autoimmune diseases and
      haematological malignancies, we studied 39,908 cases of leukaemia, Hodgkin's
      disease, non-Hodgkin's lymphoma and myeloma that occurred during 1987-1999 in
      Sweden, and 149,344 controls. Hospital discharge diagnoses of psoriasis,
      Sjogren's syndrome, autoimmune haemolytic anaemia, idiopathic thrombocytopenic
      purpura, pernicious anaemia, multiple sclerosis, rheumatic fever or asthma from
      1969 to 1999 were retrieved from the Swedish Hospital Discharge Registry.
      Psoriasis was positively associated with leukaemia, excluding chronic lymphocytic
      leukaemia, (odds ratio [OR]=1.6, 95% confidence interval [CI] 1.1-2.3) and non
      Hodgkin's lymphoma (OR=1.6, 95% CI 1.3-2.1). Sjogren's syndrome increased the
      risks of all haematological malignancies combined (OR=4.0, 95% CI 2.3-7.0), and
      of non-Hodgkin's lymphoma (OR=6.4, 95% CI 3.5-12). These findings, together with
      increased risks of several haematological malignancies in autoimmune haemolytic
      anaemia and idiopathic thrombocytopenic purpura but not in asthma, suggest
      chronic autoimmunity and immune stimulation as mechanisms contributing to the
      development of haematological malignancies.

PMID- 16945523
TI  - Trends in stomach cancer mortality in relation to living conditions in childhood.
      A study among cohorts born between 1860 and 1939 in seven European countries.
AB  - AIM: To assess whether secular trends in stomach cancer mortality were correlated
      with trends in infant mortality rate (IMR) or gross domestic product (GDP).
      METHODS: Data from seven European countries were analyzed. We used Poisson
      regression to describe mortality trends among birth cohorts of 1865-1939 and
      correlation coefficients to determine associations with IMR/GDP. RESULTS: Large
      differences were observed between birth cohorts in mortality from stomach cancer.
      In each country, these cohort differences were closely related to IMR/GDP levels
      at birth time. However, stronger associations were observed with measures of
      living conditions during later life. In comparisons between countries, stomach
      cancer mortality rates were not consistently related to national levels of
      IMR/GDP. CONCLUSION: General living conditions in childhood do not seem to have
      had a predominant effect on secular trends in stomach cancer mortality. The
      mortality decline is likely to be related to more 1specific factors, such as
      declining Helicobacter pylori prevalence.

PMID- 16945524
TI  - Discovery of potent inhibitors of pseudomonal quorum sensing via pharmacophore
      modeling and in silico screening.
AB  - HipHop-Refine was employed to derive a binding hypothesis for pseudomonal quorum
      sensing (QS) antagonists. The model was employed as 3D search query to screen the
      National Cancer Institute (NCI) database. One of the hits illustrated nanomolar
      QS inhibitory activity. The fact that this compound contained tetravalent lead
      (Pb) prompted us to evaluate the activities of phenyl mercuric nitrate and
      thimerosal, both fit the binding pharmacophore. The two mercurials illustrated
      nanomolar to low micromolar IC50 inhibitory values against pseudomonal QS. The
      three compounds represent a new class of QS inhibitors.

PMID- 16945525
TI  - Synthesis and in vitro pharmacological studies of new C(4)-modified salvinorin A
      analogues.
AB  - Salvinorin A, a compound isolated from the plant Salvia divinorum, is a potent
      and highly selective agonist for the kappa opioid receptor. For exploration of
      its structure and activity relationships, further modifications, such as
      reduction at the C(4) position, have been studied and a series of salvinorin A
      derivatives were prepared. These C(4)-modified salvinorin A analogues were
      screened for binding and functional activities at the human kappa-opioid receptor
      and several new full agonists have been identified.

PMID- 16945526
TI  - Novel thienopyrrole glycogen phosphorylase inhibitors: synthesis, in vitro SAR
      and crystallographic studies.
AB  - Two series of novel thienopyrrole inhibitors of recombinant human liver glycogen
      phosphorylase a (GPa) which are effective in reducing glucose output from rat
      hepatocytes are described. Representative compounds have been shown to bind at
      the dimer interface site of the rabbit muscle enzyme by X-ray crystallography.

PMID- 16945527
TI  - In vitro inhibitory activity of boropinic acid against Helicobacter pylori.
AB  - In this study, we assessed in vitro minimum inhibitory concentration (MIC) values
      of some natural geranyloxycoumarins, geranyloxy- and isopentenyloxy acids against
      growth of Helicobacter pylori. Boropinic acid, active principle isolated from
      Boronia pinnata (Fam. Rutaceae), was seen to be the most effective compound with
      a MIC value of 1.62 microg/mL.

PMID- 16945528
TI  - Sesquiterpene lactones are potent and irreversible inhibitors of the
      antibacterial target enzyme MurA.
AB  - We report the identification of the sesquiterpene lactones cnicin and
      cynaropicrin as potent, irreversible inhibitors of the bacterial enzyme MurA.
      They covalently bind to the thiol group of Cys115. Judging from the structure
      activity relationships, we conclude that the unsaturated ester side chain of
      cynaropicrin and cnicin is of particular importance for the inhibition of MurA.
      These results provide evidence that MurA is a target protein of SLs with a
      probably high relevance for their known antibacterial effect.

PMID- 16945530
TI  - Syntheses and studies of quinolone-cephalosporins as potential anti-tuberculosis
      agents.
AB  - The syntheses and anti-tuberculosis activity of quinolone-cephalosporin
      conjugates (1 and 2) are described. Both showed broad-spectrum antibacterial
      activity and significant anti-TB activity. The carbamate-linked quinolone-cephem
      2 showed better antimycobacterial activity, including anti-TB activity, than the
      direct amine-linked quinolone-cephem 1, while quinolone-cephem 1 was slightly
      more effective against some Gram-negative bacterial strains.

PMID- 16945529
TI  - 6-Hydroxy- and 6-methoxy-beta-carbolines as acetyl- and butyrylcholinesterase
      inhibitors.
AB  - In the course of studies directed toward the discovery of novel acetyl- and
      butyrylcholinesterase (AChE and BChE) inhibitors for the treatment of Alzheimer's
      disease, we focused on beta-carbolines (BCs). 6-Oxygenated beta-carboline and
      beta-carbolinium derivatives based on the serotonin template were synthesized and
      tested in vitro for their ability to inhibit AChE and BChE, respectively.
      Particularly the carbolinium salts, which can be formed by intracerebral
      methylation out of the tertiary-BC prodrugs, show inhibitory activity levels
      reaching those of galantamine, physostigmine, and rivastigmine.

PMID- 16945531
TI  - A novel oxazine ring closure reaction affording (Z)-((E)-2-styrylbenzo[b]furo[3,2
      d][1,3]oxazin-4-ylideno)acetaldehydes and their anti-osteoclastic bone resorption
      activity.
AB  - A novel oxazine ring formation method was established using the reaction of 2
      acetyl-(E)-3-styrylcarbonylaminobenzo[b]furans (4) with Vilsmeier-Haack-Arnold
      reagent to afford (E and Z)-((E)-2-styrylbenzo[b]furo[3,2-d][1,3]oxazin-4
      ylideno)acetaldehydes (5). (Z)-4-(8-Bromo-(E)-2-styrylbenzo[b]furo[3,2
      d][1,3]oxazin-4-ylideno)but-(E)-2-enoic acid ethyl ester (6b), derived from (Z)
      5a, showed significantly potent anti-osteoclastic bone resorption activity
      comparable to 17beta-estradiol (E2).

PMID- 16945532
TI  - Interaction of N1-unsubstituted and N1-benzenesulfonyltryptamines at h5-HT6
      receptors.
AB  - Despite possessing a common tryptaminergic scaffold, examination of 28 (i.e., 14
      pairs of) compounds suggests that N1-unsubstituted and N1
      benzenesulfonyltryptamines likely bind at h5-HT6 receptors in a dissimilar manner
      (r2=0.201). Additionally, an examination of two rotationally constrained N1
      benzenesulfonyltryptamine analogs indicates that a non-coplanar relationship
      between the two aryl groups might be preferred for interaction with the
      receptors.

PMID- 16945533
TI  - p38 MAP kinase inhibitors. Part 6: 2-arylpyridazin-3-ones as templates for
      inhibitor design.
AB  - p38 inhibitors based on 3,4-dihydropyrido[4,3-d]pyrimidazin-2-one template were
      synthesized and their SAR explored. Benchmark compounds 30, 35, and 36 were found
      to be potent against the enzyme. Crystal structure of p38 in complex with 30
      indicated a key pi-stacking interaction with the pendant tyrosine residue-35 in
      the glycine-rich loop.

PMID- 16945534
TI  - p38 MAP kinase inhibitors. Part 5: discovery of an orally bio-available and
      highly efficacious compound based on the 7-amino-naphthyridone scaffold.
AB  - A new sub-class of p38 inhibitors represented by 7-amino-naphthyridone have been
      discovered. Benchmark compound 16 potently inhibited p38 in vitro, was
      functionally active, and displayed excellent pharmacokinetic profiles in two
      animal species. Compound 16 reduced inflammation in animal disease models at
      EC(50) doses as low as 0.2mpk.

PMID- 16945535
TI  - Workshop on the nuclear envelope and Emery-Dreifuss muscular dystrophy 29th March
      2006, Oswestry, UK.

PMID- 16945537
TI  - Fatal hypertrophic cardiomyopathy and nemaline myopathy associated with ACTA1
      K336E mutation.
AB  - We report on a 2-year-old male child with both nemaline myopathy and hypertrophic
      cardiomyopathy (HCM). Sequencing of the ACTA1 gene showed a "de novo" missense
      heterozygous mutation a>g in exon 7 (Lys336Glu). Two-dimensional electrophoresis
      showed 28% mutant actin present in his muscle biopsy. Actin was isolated from the
      muscle biopsy and examined by in vitro motility assay. The sliding speed was 13+/
      3% less than normal and the affinity of actin for the Z-line protein alpha
      actinin was reduced 10 fold. This is the first report on a hypertrophic
      cardiomyopathy associated with nemaline myopathy and an ACTA1 mutation.

PMID- 16945536
TI  - Severe nemaline myopathy caused by mutations of the stop codon of the skeletal
      muscle alpha actin gene (ACTA1).
AB  - Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal
      muscle alpha-actin (ACTA1) genes. Here we report for the first time three
      patients with severe nemaline myopathy and mutations of the ACTA1 stop codon:
      TAG>TAT (tyrosine), TAG>CAG (glutamine) and TAG>TGG (tryptophan). All three
      mutations will cause inclusion of an additional 47 amino acids, translated from
      the 3' UTR of the gene, into the mature actin protein. Western blotting of one
      patient's muscle demonstrated the presence of the larger protein, while
      expression of one of the other mutant proteins fused to EGFP in C2C12 cells
      demonstrated the formation of rod bodies.

PMID- 16945538
TI  - Age-related differences in foot structure and function.
AB  - The aim of this study was to compare foot characteristics and plantar force and
      pressure patterns in young and older people. Fifty young (mean age 20.9+/-2.6
      years) and 50 older (mean age 80.2+/-5.7 years) people without foot problems
      underwent tests of foot posture, range of motion, strength, sensation and
      deformity. Plantar force and pressure distribution during gait were evaluated
      using a floor-mounted resistive sensor mat system. Older participants exhibited
      flatter/more pronated feet, reduced range of motion of the ankle and 1st
      metatarsophalangeal joints, a higher prevalence of hallux valgus, toe deformities
      and toe plantarflexor weakness, and reduced plantar tactile sensitivity. Plantar
      pressure analysis revealed decreased magnitude of forces and pressures under the
      heel (-13% to 16%), metatarsophalangeal joints (-11% to 16%) and hallux (-19% to
      25%), but greater relative contact time under the heel (+21%), midfoot (+14%) and
      metatarsophalangeal joints (+5% to 8%) in older participants. Multiple regression
      analysis revealed that these age-related differences could be largely explained
      by differences in step length and various foot characteristics, particularly foot
      posture and the severity of hallux valgus. These findings indicate that ageing is
      associated with significant changes in foot characteristics which contribute to
      altered plantar loading patterns during gait.

PMID- 16945539
TI  - Molybdenocene-oligonucleotide binding study at physiological pH using NMR
      spectroscopy and cyclic voltammetry.
AB  - The self-complementary oligonucleotide CGCATATATGCG was used as a model to
      establish the binding interactions of antitumor molybdenocene dichloride and DNA.
      The free dodecamer was first characterized using (1)H, NOESY, and DQF-COSY NMR
      experiments, which enable to pinpoint the guanines and adenines as well as the
      cytosines and thymines signals in the aromatic region. Molybdenocene dichloride
      was characterized in saline and buffer solutions as function of pH by (1)H NMR
      spectroscopy. In 10mM NaCl/D(2)O solution at pH of 6.5 and above,
      Cp(2)Mo(OD)(D(2)O)(+) is in equilibrium with its dimeric species, [Cp(2)Mo(mu
      OH)(2)MoCp(2)](2+). In 25mM Tris/4mM NaCl/D(2)O at physiological pH, a new stable
      species is formed, coordinated by the buffer, Tris(hydroxymethyl)aminomethane.
      The interactions of molybdenocene dichloride species with CGCATATATGCG were
      studied at different pH. At pH 6.5, in 4mM NaCl/D(2)O solution, (1)H NMR spectra
      of CGCATATATGCG exhibit downfield shifts in the signals associated mainly to
      adenines and guanines, upon addition of molybdenocene dichloride. At pH 7.4, in
      25mM Tris/4mM NaCl/D(2)O, molybdenocene species causes broadening and small
      downfield shifts to the purines and pyrimidine signals, suggesting that
      molybdenocene dichloride can get engaged in binding interactions with the
      oligonucleotide in a weak manner. (31)P NMR spectra of these interactions at pH
      7.4 showed no changes associated to Mo(IV)-OP coordination, indicating that
      molybdenocene-oligonucleotide binding interactions are centered, most likely, on
      the bases. Cyclic voltammetry titration showed a 4.9% of molybdenocene
      oligonucleotide interaction. This implicates that possible binding interactions
      with DNA are weak.

PMID- 16945540
TI  - QSAR study of antiplatelet agents.
AB  - A QSAR methodology that involves multilinear (Hansch-type) and nonlinear (ANN
      backpropagation) approaches was developed to correlate the antiplatelet activity
      of 60 benzoxazinone derivatives against factor Xa. The statistical
      characteristics provided by multilinear model (R2 = 0.821) indicated satisfactory
      stability and predictive ability, while the ANN predictive ability is somewhat
      superior (R2 = 0.909). The multilinear model provided insight into the main
      factors that modulate the inhibitory activity of the investigated compounds.

PMID- 16945541
TI  - A cationic chalcogenoxanthylium photosensitizer effective in vitro in
      chemosensitive and multidrug-resistant cells.
AB  - Pentacyclic thio- (1) and seleno- (2) analogues of tetramethylrosamine (TMR) were
      prepared with a julolidyl fragment replacing the 3-dimethylamino substituent in
      the xanthylium core. The pentacylic structure increases the lipophilicity of 1
      and 2 relative to TMR-S and TMR-Se and locks the lone-pair of electrons on the
      julolidyl N atom into conjugation with the xanthylium core. This conformational
      rigidization leads to longer wavelengths of absorption, but has little impact on
      other photophysical properties such as quantum yields for fluorescence and
      singlet-oxygen generation and fluorescence lifetimes in 1 and 2 relative to TMR-S
      and TMR-Se. Both 1 and 2 are effective photosensitizers against chemosensitive
      AUXB1 cells in vitro at 1x10(-7)M and compound 2 is an effective photosensitizer
      against multidrug-resistant CR1R12 cells in vitro at 1x10(-7)M. While the uptake
      TMR-S into CR1R12 cells as measured by fluorescence is significantly lower than
      uptake into chemosensitive AUXB1 cells, there is no significant difference in the
      uptake of 1 into either AUXB1 or CR1R12 cells. The addition of 2x10(-4)M
      verapamil to the cells prior to treatment with 1 had no significant effect on the
      uptake of 1 into either AUXB1 or CR1R12 cells. Treating lipid-activated, purified
      Pgp with 2 and light gave complete inhibition of Pgp ATPase activity.

PMID- 16945542
TI  - Synthesis of 2,4,6-trisubstituted pyrimidine and triazine heterocycles as
      antileishmanial agents.
AB  - A series of 2,4,6 trisubstituted pyrimidines and triazines have been synthesized
      and screened for its in vitro antileishmanial activity profile in promastigote
      model. Nine compounds have shown > 94% inhibition against promastigotes at a
      concentration of 10 microg/mL.

PMID- 16945543
TI  - Structure-activity relationship of wedelolactone analogues: structural
      requirements for inhibition of Na+, K+ -ATPase and binding to the central
      benzodiazepine receptor.
AB  - Coumestans 2a-i, bearing different patterns of substitution in A- and D-rings,
      were synthesized and evaluated as inhibitors of kidney Na+, K+ -ATPase and
      ligands for the central benzodiazepine (BZP) receptor. The presence of a hydroxyl
      group in position 2 favours the effect on Na+, K+ -ATPase but decreases the
      affinity for the BZP receptor, allowing the design of more selective molecules
      than the natural wedelolactone. On the other hand, the presence of a catechol in
      ring D is important for the effect on both molecular targets.

PMID- 16945545
TI  - Speckle random coding for 2D super resolving fluorescent microscopic imaging.
AB  - In this manuscript we present a novel super resolving approach based upon
      projection of a random speckle pattern onto samples observed through a
      microscope. The projection of the speckle pattern is created by coherent
      illumination of the inspected pattern through a diffuser. Due to local
      interference of the coherent wave front with itself, a random speckle pattern is
      superimposed on the sample. This speckle pattern can be scanned over the object.
      A super-resolved image can be extracted from a temporal sequence of images by
      appropriate digital processing of the image stream. The resulting resolution is
      significantly higher than the diffraction limitation of the microscope objective.
      The new super-resolution method is demonstrated by application to fluorescence of
      biological samples.

PMID- 16945544
TI  - Solid-phase synthesis of positively charged deoxynucleic guanidine (DNG)
      oligonucleotide incorporating 7-deazaguanine bases.
AB  - DNG nucleotides represent a positively charged DNA analog in which the negatively
      charged phosphodiester linkages of DNA are replaced by positively charged
      guanidinium linkages. We report herein the synthesis of 3'-end, middle, and 5'
      end monomers required for the synthesis of a DNG sequence in which the natural
      guanine base is replaced by 7-deazaguanine (c(7)G). 7-Deazaguanine nucleobase was
      chosen because of their unique glycoside bond stability and their ability to
      prevent G-quartet formation. A facile and high yield two-step synthesis of xylo-7
      deazaguanine 7, a key intermediate for introducing 3'-amino functionality, is
      carried out under Mitsunobu conditions. Subsequently, the 3'-Fmoc-protected
      thiourea monomers 13 and 19 were prepared from 7 via their corresponding 3'-amino
      7-deazaguanines 11 and 18, respectively. The smooth coupling of these thiourea
      monomers with monomethoxytrityl (MMTr)-protected 3'-end monomer 25, prepared from
      5, occurred on solid phase in 3'-->5' direction. The resultant trimeric HO
      c(7)Ggc(7)Ggc(7)G-OH (1) has been designed to be included into DNA using standard
      DNA synthesis technology. The combination of C-c(7)G base pairing and
      electrostatic association of phosphodiester and guanidinium backbone allows the
      small synthesized DNG trimer 1 to form 1:1 complex with DNA-C pentamer.

PMID- 16945546
TI  - Calibration of HPGe gamma-ray detectors for measurement of radioactive noble gas
      sources.
AB  - Measurements of radioactive noble gases are routinely made with gamma-ray
      spectrometers. This work describes the calibration of high purity germanium
      detectors provided by the full-energy-peak efficiency as a function of the gamma
      ray energy. A comparison of measured efficiency values with a new, simplified
      method based on a direct mathematical method is given here.

PMID- 16945547
TI  - Magnetic resonance-fluoroscopy as long-term follow-up examination in patients
      with narrow gastric tube reconstruction after radical esophagectomy.
AB  - OBJECTIVE: To evaluate the functionality and morphology of neo-esophagus in
      subjects who underwent narrow gastric tube (NGT) reconstruction after total
      esophagectomy using magnetic resonance (MR)-fluoroscopy with Turbo-FLASH
      sequences acquired during positive oral contrast agent administration. METHODS
      AND MATERIALS: Ten patients, who underwent NGT reconstruction after total
      esophagectomy between 2002 and 2004, were studied using a 1.5 T magnet (Magnetom
      Avanto: Siemens, Erlangen, Germany, featuring total imaging matrix-TIM
      technology), equipped with surface phased-array and integrated spine coils.
      Imaging protocol included TRUFI and Turbo-FLASH sequences (TR=600 ms; TE=1.3 ms;
      Flip Angle 8 degrees ; Thickness 20 mm; FoV 350; Matrix 128 x 256; N. acquisition
      120; TA=50 s) acquired on sagittal and axial planes to achieve motility
      evaluation during oral administration of positive contrast agent (yoghurt+Gd-DTPA
      0.5M, 1:100 boluses). RESULTS: Good quality images were obtained in all patients,
      with adequate lumen contrast and a frame rate of 2.5 frames per second (fps).
      Three patients had completely re-established motility of NGT; six patients had
      mild to moderate alterations including raised transit time, reflux and contrast
      agent stasis; one patient had severe alterations with grossly dilated NGT, severe
      reflux and stasis. CONCLUSIONS: MR-fluoroscopy approach represents a promising
      radiation-free modality in the evaluation of functionality and morphology of NGT.
      Further investigation in the evaluation of post-surgery patients is necessary.

PMID- 16945548
TI  - Fractionated illumination after topical application of 5-aminolevulinic acid on
      normal skin of hairless mice: the influence of the dark interval.
AB  - We have previously shown that light fractionation during topical aminolevulinic
      acid based photodynamic therapy (ALA-PDT) with a dark interval of 2h leads to a
      significant increase in efficacy in both pre-clinical and clinical PDT. However
      this fractionated illumination scheme required an extended overall treatment
      time. Therefore we investigated the relationship between the dark interval and
      PDT response with the aim of reducing the overall treatment time without reducing
      the efficacy. Five groups of mice were treated with ALA-PDT using a single light
      fraction or the two-fold illumination scheme with a dark interval of 30 min, 1,
      1.5 and 2h. Protoporphyrin IX fluorescence kinetics were monitored during
      illumination. Visual skin response was monitored in the first seven days after
      PDT and assessed as PDT response. The PDT response decreases with decreasing
      length of the dark interval. Only the dark interval of 2h showed significantly
      more damage compared to all the other dark intervals investigated (P<0.05
      compared to 1.5h and P<0.01 compared to 1h, 30 min and a single illumination). No
      relationship could be shown between the utilized PpIX fluorescence during the two
      fold illumination and the PDT response. The rate of photobleaching was comparable
      for the first and the second light fraction and not dependent of the length of
      dark interval used. We conclude that in the skin of the hairless mouse the dark
      interval cannot be reduced below 2h without a significant reduction in PDT
      efficacy.

PMID- 16945549
TI  - Non-steroidal anti-inflammatory drugs to potentiate chemotherapy effects: from
      lab to clinic.
AB  - Most solid tumors express the cyclooxygenase-2 (COX-2) protein, a target of
      NSAIDs. COX-2 overexpression in tumorsis considered a predictor of more advanced
      stage disease and of worse prognosis in a number of studies investigating solid
      malignancies. Therefore, NSAIDs are evaluated as anti-cancer drugs. NSAIDs
      inhibit proliferation, invasiveness of tumors, and angiogenesis and overcome
      apoptosis resistance in a COX-2 dependent and independent manner. This review
      will focus on the rationale behind NSAIDs, including selective COX-2 inhibitors,
      in combination with conventional chemotherapeutic drugs or novel molecular
      targeted drugs. Studies investigating anti-cancer effects of NSAIDs on cell lines
      and xenograft models have shown modulation of the Akt, NF-kappaB, tyrosine kinase
      and the death receptor-mediated apoptosis pathways. COX-2 expression in tumors is
      not yet used as biomarker in the clinic. Despite the increased risk on
      cardiovascular toxicity induced by selective COX-2 inhibitors, several ongoing
      clinical trials are still investigating the therapeutic benefits of NSAIDs in
      oncology. The anti-tumor effects in these trials balanced with the side effects
      data will define the precise role of selective COX-2 inhibitors in the treatment
      of cancer patients.

PMID- 16945550
TI  - Molecular markers in the diagnosis of prostate cancer.
AB  - The genetic alterations leading to prostate cancer are gradually being
      discovered. A wide variety of genes have been associated with prostate cancer
      development as well as tumor progression. Knowledge of gene polymorphisms
      associated with disease aid in the understanding of important pathways involved
      in this process and may result in the near future in clinical applications.
      Urinary molecular markers will soon be available to aid in the decision of repeat
      prostate biopsies. Recent findings suggest the importance of androgen signaling
      in disease development and progression. The further understanding of interaction
      of inflammation, diet, and genetic predisposition will improve risk
      stratification in the near future.

PMID- 16945551
TI  - Old and new perspectives in the management of high-risk, locally advanced or
      recurrent, and metastatic vulvar cancer.
AB  - During the last decades there has been a continuing evolution in the surgical
      approach of squamous cell carcinoma of the vulva that has been traditionally
      treated with radical vulvectomy and bilateral inguinal-femoral lymphadenectomy.
      Patients with T1 tumour are usually treated with radical local excision, if the
      lesion is unifocal and the remainder of the vulva is normal. Patients with T1a
      disease have no risk of groin metastases and do not need lymphadenectomy, whereas
      those with T1b disease need ipsilateral inguinal-femoral lymphadenectomy if the
      lesion is lateral, and bilateral lymphadenectomy if the lesion is midline.
      Modifications of the surgical technique of deep femoral lymphadenectomy and the
      mapping of sentinel node can offer new interesting therapeutic perspectives.
      Postoperative adjuvant pelvic and groin irradiation is warranted for patients
      with two or more or macroscopically involved groin nodes. Locally advanced
      squamous cell carcinoma of the vulva has been long surgically treated with en
      block radical vulvectomy and bilateral inguinal-femoral lymphadenectomy plus
      partial resection of urethra, vagina or anum, or by exenteration, with severe
      postsurgical complications, poor quality of life, and unsatisfactory survival
      rates. 5-Fluorouracil [5-FU] or 5-FU- and cisplatin-based chemotherapy concurrent
      with irradiation followed by tailored surgery represents an attractive
      therapeutic option for advanced disease, planned to avoid such ultra-radical
      surgical procedures and, hopefully, to improve patient outcome. Chemotherapy has
      also been used in neoadjuvant setting, with contrasting and generally
      unsatisfactory results, and in palliative treatment of patients with distant
      metastases. Surgery is the primary treatment also for vulvar malignancies other
      than squamous cell carcinoma, whereas the clinical usefulness of adjuvant
      irradiation or chemotherapy is still to be defined. Primary chemoradiation can be
      also used for advanced carcinoma of the Bartholin gland or for advanced
      adenocarcinoma associated with extramammary Paget's disease. The drugs used for
      chemotherapy of metastatic melanomas or sarcomas of the vulva are the same
      employed for the melanomas or sarcomas developed in other sites.

PMID- 16945552
TI  - The Oscar-worthy role of Myc in apoptosis.
AB  - The discovery that the Myc oncoprotein could drive cells to undergo apoptosis in
      addition to its well-established role in cellular proliferation came in the early
      1990s, at the beginning of a period of explosive research on cell death.
      Experimental evidence revealed that Myc sensitises cells to a wide range of death
      stimuli and abrogating this biological activity plays a profound role in
      tumorigenesis. Our understanding of the molecular mechanism and genetic programme
      of Myc-induced apoptosis remains shrouded in mystery and the focus of much
      attention. In this review, we will discuss established data, recent advances and
      future objectives regarding the regulatory processes and the functional
      cooperators that effect and abrogate apoptosis induced by Myc.

PMID- 16945553
TI  - Spatially weighted BOLD signal for comparison of functional magnetic resonance
      imaging and near-infrared imaging of the brain.
AB  - We introduce a weighted spatial average of the functional magnetic resonance
      imaging (fMRI) BOLD signal (blood oxygen level-dependent) that is appropriate for
      comparison with the changes in oxy- and deoxy-hemoglobin concentrations measured
      with near-infrared spectroscopy (NIRS) during brain activation. Because the BOLD
      signal shows a spatial dependence (both in shape and amplitude) within the region
      of activation, the location of the optical probe with respect to the region of
      BOLD activation should be taken into account for comparison of the BOLD and NIRS
      signals. Our new method is based on combining weighted contributions of the BOLD
      signal from each activated voxel, with a weight given by a hitting density
      function for photons migrating between a given pair of illumination and
      collection points. We present a case study where we have found that the new
      spatially weighted BOLD signal shows a high spatial and temporal correlation with
      the oxy- and deoxy-hemoglobin concentration changes measured with NIRS during a
      hand-tapping protocol. These findings reinforce the idea that fMRI and NIRS are
      sensitive to similar underlying hemodynamic changes, and indicate that the
      proposed weighted BOLD signal is needed for a quantitative comparison of BOLD and
      NIRS signals.

PMID- 16945554
TI  - Translating DNA data tables into quasi-median networks for parsimony analysis and
      error detection.
AB  - Every DNA data table can be turned into a quasi-median network that faithfully
      represents the data. We show that for (weighted) condensed data tables the
      associated network harbors all most parsimonious reconstructions for any tree
      that connects the sampled haplotypes. Structural features of this network can be
      computed directly from the data table. The key principle repeatedly used is that
      the quasi-median network is uniquely determined by the sub-tables for pairs of
      characters. The translation of a table into a network enhances the understanding
      of the properties of the data in regard to homoplasy and potential artifacts. The
      total number of nodes of such a network measures the complexity of the data. In
      particular, networks that display the results of filter analyses by which hotspot
      mutations are removed help to detect data idiosyncrasies and thus pinpoint
      sequencing problems. A pertinent example drawn from human mtDNA illustrates these
      points.

PMID- 16945555
TI  - Convergent evolution of gigantism in damselflies of Africa and South America?
      Evidence from nuclear and mitochondrial sequence data.
AB  - Extreme large body size is rare in modern Zygoptera (damselflies). Only the South
      and Central American damselfly family Pseudostigmatidae and one African species,
      Coryphagrion grandis, share the morphological trait of gigantism. By means of
      phylogenetic analyses using two mitochondrial markers (16S rDNA and ND1) and one
      nuclear marker (EF1) in combination with an existing morphological data set, we
      trace the evolution of gigantism in damselflies. Individual and combined data
      sets were analyzed using the maximum parsimony, minimum evolution and maximum
      likelihood algorithms. Regardless of the algorithm used and the data set analyzed
      all principal tree topologies support a monophyly of the damselfly taxa
      displaying giant body size. This supports the view that the evolution of
      gigantism in damselflies from Africa and South America is not the result of
      convergent evolution due to strikingly similar habitat preferences, but rather
      the result of close genealogical relationship. Because modern odonates evolved
      before the split of Africa from Gondwanaland, the proposed phylogeny suggests
      that C. grandis represents a Gondwana relict.

PMID- 16945556
TI  - A northward colonisation of the Andes by the potato cyst nematode during
      geological times suggests multiple host-shifts from wild to cultivated potatoes.
AB  - The cyst nematode Globodera pallida is a major pest of potato in South America
      where this specialist parasite is native. To investigate its phylogeography, we
      have genotyped individuals from 42 Peruvian populations using mitochondrial and
      nuclear molecular markers. A clear south-to-north phylogeographical pattern was
      revealed with five well-supported clades. The clade containing the southern
      populations is genetically more diverse and forms the most basal branch. The
      large divergence among cytochrome b haplotypes suggests that they diverged before
      human domestication of potato. As the nematodes studied have been sampled on
      cultivated potato, multiple host-shifts from wild to cultivated potatoes must
      have occurred independently in each clade. We hypothesise that this south-to
      north pattern took place during the uplift of the Andes beginning 20 My ago and
      following the same direction. To our knowledge, this is the first study of a
      plant parasite sampled on cultivated plants revealing an ancient
      phylogeographical pattern.

PMID- 16945557
TI  - Upper extremity deep venous thrombosis after shoulder arthroscopy: a case report.

PMID- 16945558
TI  - Traumatic subacromial dislocation of the acromioclavicular joint: a case report.

PMID- 16945559
TI  - Possible involvement of the oxidized low-density lipoprotein/lectin-like oxidized
      low-density lipoprotein receptor-1 system in pathogenesis and progression of
      human osteoarthritis.
AB  - OBJECTIVE: Using human cartilage samples and cultured chondrocytes, to assess the
      possible involvement of oxidized low-density lipoprotein (ox-LDL) and lectin-like
      ox-LDL receptor-1 (LOX-1) in pathogenesis and progression of osteoarthritis (OA).
      METHODS: Thirty-two cartilage samples were obtained from 16 patients with knee
      OA, and 12 Control samples from six with femoral neck fracture. LOX-1 mRNA
      expressions in 12 OA and six Control samples were analyzed by reverse
      transcription-polymerase chain reaction (RT-PCR). Immunohistochemistry for ox-LDL
      and LOX-1 was performed in all samples. The histological OA grade was assessed
      with the modified Mankin score. The relative percentage of the ox-LDL and LOX-1
      immunopositive chondrocytes was calculated in all samples. The effects of ox-LDL
      on cell viability in cultured human chondrocytes were investigated by the 3-(4,5
      dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay and on
      proteoglycan synthesis by monitoring [35S] sulfate incorporation. RESULTS: There
      was a statistically significant difference between mean LOX-1/GAPDH (LOX-1/human
      glyceraldehyde-3-phosphate dehydrogenase) ratio of OA samples and that of Control
      samples (40.6%+/-10.3 and 11.9%+/-2.8, respectively, P<0.0001). The mean
      percentage of ox-LDL-positive cells was 23.0+/-15.7% in OA and 4.3+/-3.7% in
      Control cells (P=0.0002). The mean percentage of LOX-1-positive cells was 51.7+/
      29.5% in OA and 10.0+/-8.1% in Control cells (P<0.0001). Both the ox-LDL
      immunoreactivity and the LOX-1 immunoreactivity were significantly correlated
      with the modified Mankin scores (R2=0.67 and 0.48, respectively; P<0.0001 for
      each). ox-LDL significantly reduced the human chondrocyte viability and
      proteoglycan synthesis, and pretreatment with anti-human LOX-1 monoclonal
      antibody reversed these effects. CONCLUSION: The ox-LDL/LOX-1 system may be
      involved in human OA.

PMID- 16945560
TI  - The effects of diet on blood glucose, insulin, gastrin and the serum tryptophan:
      large neutral amino acid ratio in foals.
AB  - High carbohydrate diets can affect the health and behaviour of foals, but the
      mechanisms are not always fully understood. The objective of this study was to
      compare the effects of feeding a starch and sugar (SS), or a fat (oil) and fibre
      (FF) rich diet to two groups of eight foals. Diets were fed from 4 to 42 weeks of
      age, alongside ad libitum forage. Faecal pH levels did not differ significantly
      between groups and endoscopic examination showed that the gastric mucosa was
      healthy in both groups at 25 and 42 weeks of age. At 40 weeks of age, SS foals
      had significantly higher total blood glucose and lower total blood gastrin than
      FF foals during the 6h period following ingestion of their respective diets, but
      insulin levels did not differ significantly. The ratio between serum tryptophan
      and other large neutral amino acids showed a trend towards an interaction between
      diet and sampling time. The results provide preliminary information about the
      effects of diet on the physiology of young horses.

PMID- 16945561
TI  - Ultra-low field NMR measurements of liquids and gases with short relaxation
      times.
AB  - Interest in nuclear magnetic resonance measurements at ultra-low magnetic fields
      (ULF, approximately microT fields) has been motivated by various benefits and
      novel applications including narrow NMR peak-width, negligible susceptibility
      artifacts, imaging of samples inside metal containers, and possibility of
      directly imaging neuronal currents. ULF NMR/MRI is also compatible with
      simultaneous measurements of biomagnetic signals. However the most widely used
      technique in ULF NMR-prepolarization at high field and measurement at lower field
      results in large transient signals which distort the free induction decay signal.
      This is especially severe for the measurement of signals from samples and
      materials with short T1 time. We have devised an approach that largely cancels
      the transient signals. The technique was successfully used to measure NMR signals
      from liquids and gases with T1 in the range 1-4 ms.

PMID- 16945562
TI  - Cloning of chicken lanosterol 14alpha-demethylase (CYP51) cDNA: discovery of a
      testis-specific CYP51 transcript.
AB  - A lanosterol 14alpha-demethylase (CYP51) cDNA, which consisted of a 1419 bp open
      reading frame encoding 472 amino acids and a 918 bp 3'-untranslated region, was
      isolated from the chicken testis. The sequence corresponding to exon 1 of this
      cDNA was completely different from those of CYP51 cDNAs in other tissues,
      including the liver. The expression level of the CYP51 gene with the testis
      specific exon 1 was much higher in mature (2-year-old) male chickens than in
      immature (5-week-old) chickens. In addition, a CYP51 transcript common to several
      tissues, including the liver, adrenal gland, cerebellum, cerebrum, lobus opticus,
      kidney, lung, heart, muscle, spleen, small intestine and ovary, was also detected
      in the testis by RT-PCR. Furthermore, testis-specific shorter transcripts, which
      have been observed in mammals such as humans, rats and pigs, were not detected in
      the chicken testis. The results of this study demonstrate for the first time the
      presence of a chicken testis-specific CYP51 transcript and its sexual maturation
      related expression, although its biological significance remains unclear.

PMID- 16945563
TI  - Blood-gas properties of plateau zokor (Myospalax baileyi).
AB  - Plateau zokor (Myospalax baileyi) is one of the blind subterranean mole rats that
      spend their life solely underground in sealed burrows. It is one of the special
      species of the Qinghai-Tibet plateau. In their burrows, oxygen is low and carbon
      dioxide is high and their contents fluctuate with the change of seasons, soil
      types, rain and depth of burrows. However, plateau zokors show successful
      adaptation to that extreme environment. In this study, their adapting mechanisms
      to the hypoxic hypercapnic environment were analyzed through the comparison of
      their blood-gas properties with that of pikas (Ochotona curzniae) and Sprague
      Dawley rats. The results indicated that plateau zokors had higher red blood
      corpuscle counts (8.11+/-0.59 (10(12)/L)) and hemoglobin concentrations (147+/
      9.85 g/L), but hematocrit (45.9+/-3.29%) and mean corpuscular volume (56.67+/
      2.57 fL) were lower than the other rodents. Their arterial blood and venous blood
      pH were 7.46+/-0.07 and 7.27+/-0.07. Oxygen pressure in arterial blood of plateau
      zokors was about 1.5 times higher than that of pikas and rats, and it was 0.36
      and 0.26 times in their venous blood. Partial pressure for carbon dioxide in
      arterial and venous blood of plateau zokors was 1.5-fold and 2.0-fold higher,
      respectively, than in rats and pikas. Oxygen saturation of plateau zokors was 5.7
      and 9.3 times lower in venous blood than that of pikas and rats, respectively. As
      result, the difference of oxygen saturation in arterial blood to venous blood was
      2- and 4.5-fold higher in plateau zokors as that of pikas and rats, respectively.
      In conclusion, plateau zokors had a high tolerance to pH changes in tissues,
      together with strong capabilities to obtain oxygen from their hypoxic-hypercapnic
      environment.

PMID- 16945564
TI  - V-H(+)-ATPase, Na(+)/K(+)-ATPase and NHE2 immunoreactivity in the gill epithelium
      of the Pacific hagfish (Epatretus stoutii).
AB  - We report the presence of the ion transporting proteins V-H(+)-ATPase, Na(+)/K(+)
      ATPase and NHE2 in the gill epithelium of the Pacific hagfish Epatretus stoutii.
      Heterologous antibodies recognized single bands of the appropriate sizes for the
      three transporters in western blots. Immunohistochemical staining revealed that
      the distribution of labeled cells in the gill epithelium was identical for the
      three proteins. Immunopositive cells were most abundant in the primary filament
      from the afferent side of the gill pouch, and their number diminished towards the
      lamella. Na(+)/K(+)-ATPase-like immunoreactivity (L-IR) occurred throughout the
      cell cytoplasm, probably associated to the basolateral tubular system. V-H(+)
      ATPase L-IR was similar to Na(+)/K(+)-ATPase, although some cells had slightly
      heavier staining in either the supra- or infra-nuclear region. NHE2 L-IR was also
      generally cytoplasmic, but a minority of the cells had stronger immunoreactivity
      in the apical region. In general, all three ion transporting proteins were
      localized in the same cells, as estimated from 4-microm immunostained consecutive
      sections. We hypothesize that these putative ion-transporting cells are involved
      in systemic acid/base regulation and discuss other possible roles. This is the
      first report of V-H(+)-ATPase in myxinoids, and the first NHE2 report in the
      Pacific hagfish.

PMID- 16945565
TI  - Molecular cloning, expression, and enzymatic activity of a novel endogenous
      cellulase from the mulberry longicorn beetle, Apriona germari.
AB  - A novel endogenous beta-1,4-endoglucanase (Ag-EGase III) gene belonging to the
      glycoside hydrolase family (GHF) 5 was cloned from the mulberry longicorn beetle,
      Apriona germari. The Ag-EGase III gene spans 1061 bp and consists of a single
      exon coding for 325 amino acid residues. The Ag-EGase III showed 89% protein
      sequence identity to another beetle, Psacothea hilaris, cellulase belonging to
      GHF 5. The Ag-EGase III has the potential proton donor and nucleophile amino
      acids conserved in GHF 5 and two putative N-glycosylation sites. Northern blot
      and Western blot analyses showed that Ag-EGases were expressed in the gut; Ag
      EGase III and Ag-EGase I were expressed in three gut regions, and no Ag-EGase II
      was found in hindgut, indicating that the foregut and midgut are the prime sites
      for cellulase synthesis in A. germari larvae. The cDNA encoding Ag-EGase III was
      expressed as a 47-kDa polypeptide in baculovirus-infected insect Sf9 cells and
      the enzyme activity of the purified recombinant Ag-EGase III was approximately
      1037 U per mg of recombinant Ag-EGase III. The enzymatic property of the purified
      recombinant Ag-EGase III showed the highest activity at 55 degrees C and pH 6.0,
      and was stable at 60 degrees C at least for 10 min. In addition, the N
      glycosylation of Ag-EGase III was revealed by treatment with tunicamycin of
      recombinant virus-infected insect Sf9 cells and with endoglycosidase F of
      purified recombinant Ag-EGase III, demonstrating that the carbohydrate moieties
      are not necessary for enzyme activity.

PMID- 16945566
TI  - Palmitoylation and its effect on the GTPase-activating activity and conformation
      of RGS2.
AB  - Regulator of G protein signaling (RGS) proteins act as negative regulators of G
      protein coupled signaling by accelerating the GTPase activity of the G proteins
      alpha subunits. Reversible palmitoylation, a common post-translational
      modification for various components of the G protein-coupled signaling pathway,
      plays an important role in the modulation of protein activity. RGS2 appears to
      act selectively to increase the GTPase activity of Gqalpha when single turnover
      assays are preformed in solution. However, less attention has been paid to the
      effects of palmitoylation of RGS2 on its conformation and GTPase-activating
      activity. Studies of palmitoylation on a series of RGS2 mutants in which alanine
      was substituted for cysteine revealed cysteine 106, 116 and 199 to be multiple
      putative palmitoylation sites in RGS2, the efficiency of palmitate incorporation
      being about 60% at each individual palmitoylation site. Palmitoylation of RGS2
      inhibited the GTPase-activating activity toward a GTPase-deficient R183C mutant
      of Gqalpha in vitro, but mutation of cysteine 116 eliminated the inhibition of
      palmitoylation on GTPase-activating activity of RGS2. The effect of
      palmitoylation on conformation of RGS2 was examined by monitoring spectra of the
      intrinsic fluorescence and Circular Dichroism. The results suggested that GTPase
      activating activity change of RGS2 might be related to conformational change of
      RGS2 upon palmitoylation. Taken together, these results provided clear and strong
      experimental evidence for palmitoylation sites in RGS2 as well as for effect of
      palmitoylation on the GTPase-activating activity and conformation of RGS2.

PMID- 16945567
TI  - Chondroitin sulfate A chains enhance platelet derived growth factor-mediated
      signalling in fibrosarcoma cells.
AB  - Platelet derived growth factor is involved in the autocrine growth stimulation of
      malignant cells, the stimulation of angiogenesis and the recruitment and
      regulation of tumor fibroblasts. PDGF has been shown to physically interact with
      glycosaminoglycans which are abundant in the fibrosarcoma cell microenvironment.
      Aim of the present study was to examine the effects of glycosaminoglycans on the
      mitogenic function of platelet derived growth factor in two human fibrosarcoma
      cell lines (B6FS, HT1080). For this purpose exogenously added glycosaminoglycans,
      regulators of endogenous glycosaminoglycan synthesis (sodium chlorate as
      selective inhibitor and beta-D-xyloside as a stimulator) and specific
      glycosidases to cleave cell-associated glycosaminoglycans, were utilized.
      Platelet derived growth factor demonstrated a growth stimulating effect on B6FS,
      whereas no effect was evident on HT1080 fibrosarcoma cells. Beta-D-xyloside had
      no effect on the basal level or the platelet derived growth factor-induced cell
      proliferation, whereas sodium chlorate severely reduced the basal level of
      proliferation in both cell lines. Significant co-stimulatory effects of
      chondroitin sulfate A in combination with platelet derived growth factor BB on
      the growth of HT1080 and B6FS cells were found. The co-stimulatory effect of
      chondroitin sulfate A was not due to transcriptional up regulation of platelet
      derived growth factor receptors genes, but rather to more efficient signalling of
      tyrosine kinase receptors. In conclusion, this study shows that chondroitin
      sulfate A can enhance the mitogenic activity of platelet-derived growth factor in
      fibrosarcoma cells utilizing a pathway which involves tyrosine kinases. This
      result introduces a new modulating role for chondroitin sulfate in signalling
      pathways critical for cancer growth.

PMID- 16945568
TI  - Endothelial monocyte-activating polypeptide-II and its functions in
      (patho)physiological processes.
AB  - Endothelial monocyte-activating polypeptide-II (EMAP-II) is a pro-inflammatory
      cytokine with anti-angiogenic properties. Its precursor, proEMAP, is identical to
      the p43 auxiliary component of the tRNA multisynthetase complex and therefore
      involved in protein translation. Although most of the activities have been
      ascribed to the active form EMAP-II, also p43 has reported cytokine properties.
      ProEMAP/p43 and EMAP-II act on many levels and on many cell types including
      endothelial cells, immune cells and fibroblasts. In this review we summarize all
      available data on isolation, expression and functions of EMAP-II both in
      physiological processes as well as in pathological settings, like cancer. We also
      discuss the different reported mechanisms for processing of proEMAP/p43 into EMAP
      II. Finally, we speculate on the possible applications of this cytokine for
      (cancer) therapy.

PMID- 16945569
TI  - A biologically inspired algorithm for microcalcification cluster detection.
AB  - The early detection of breast cancer greatly improves prognosis. One of the
      earliest signs of cancer is the formation of clusters of microcalcifications. We
      introduce a novel method for microcalcification detection based on a biologically
      inspired adaptive model of contrast detection. This model is used in conjunction
      with image filtering based on anisotropic diffusion and curvilinear structure
      removal using local energy and phase congruency. An important practical issue in
      automatic detection methods is the selection of parameters: we show that the
      parameter values for our algorithm can be estimated automatically from the image.
      This way, the method is made robust and essentially free of parameter tuning. We
      report results on mammograms from two databases and show that the detection
      performance can be improved by first including a normalisation scheme.

PMID- 16945570
TI  - Acanthamoeba keratitis associated with misuse of daily disposable contact lenses.
AB  - PURPOSE: To report a case of Acanthamoeba keratitis that occurred in a daily
      disposable contact lens wearer. METHOD: Case report. RESULTS: A 70-year-old
      gentleman presented to eye casualty with a red left eye with reduced vision and
      corneal epithelial changes. Acanthamoeba keratitis was not suspected initially as
      he was a daily disposable contact lens wearer. This led to a delay of 17 days in
      initiating treatment. He responded well to topical polyhexamethylene biguanide
      and propamidine and made a full recovery. CONCLUSION: Acanthamoeba keratitis can
      occur in patients who reuse daily disposable contact lenses. A diagnosis of
      Acanthamoeba keratitis can be difficult to make and should be considered in all
      patients who wear contact lenses, including daily disposable lenses. All patients
      who wear daily disposable contact lenses should be reminded that the benefits of
      this modality of contact lens are only possible if the lenses are worn once and
      thrown away.

PMID- 16945571
TI  - Traumatic aniridia after small incision cataract extraction.
AB  - INTRODUCTION: Phacoemulsification and falls are both common in the elderly
      population. We present a case of acquired total aniridia and vitreous haemorrhage
      occurring as a result of trauma in a pseudophakic eye. METHODS: Interventional
      case report with history, clinical photograph and discussion with literature
      review. RESULTS: A previously healthy 74-year-old Caucasian female was referred
      with a painful left eye and poor vision following a fall and trauma to the left
      side of her face. Initial examination confirmed visual acuity of perception of
      light with total hyphaema and vitreous haemorrhage. Subsequent examination
      revealed complete aniridia with an intact capsular bag and well-centred posterior
      chamber intraocular lens and attached retina. Final visual acuity after treatment
      was 6/9. CONCLUSIONS: Blunt trauma may cause total iris disinsertion in and
      expulsion from pseudophakic eyes. This relatively novel injury may present
      increasingly commonly to casualty departments and ophthalmologists.

PMID- 16945572
TI  - Lens care complications--where's the rub?

PMID- 16945574
TI  - Structure and vibrations of BenOn (n=3-10) clusters.
AB  - The structure and harmonic vibrations of Be(n)O(n) (n=3-10) clusters have been
      investigated using density functional theory. All structures are found to be
      cumulenic D(nh) rings (equal bonds, alternating angles), with one intense out of
      plane mode and three infrared-active degenerate modes, of which the highest one
      is extremely intense and asymptotically increases to 1597 cm(-1) for n=10.
      Comparisons with C(2n) clusters and B(n)N(n) clusters, the structure and bonding
      type for the Be(n)O(n) clusters are consistent with those of the C(2n) (n=3, 5,
      7, ...) clusters and the B(n)N(n) clusters.

PMID- 16945575
TI  - Optical constants, dielectric constants, molar absorption coefficients, molar
      polarizability, vibrational assignment and transition moments of liquid
      iodobenzene between 4000 and 400 cm(-1) at 25 degrees C.
AB  - This paper reports the complex refractive index, molar absorption coefficient and
      imaginary molar polarizability spectra of liquid iodobenzene at 25 degrees C. The
      imaginary molar polarizability spectrum was fitted with 184 classical damped
      harmonic bands to determine the integrated intensity of the individual
      transitions. The standard deviation of the fitted spectrum from the experimental
      spectrum is 0.024 cm(3) mol(-1), and the R(2) value of the fit is 0.9968
      indicating that the fitted spectrum is an accurate representation of the
      experimental spectrum. The dipole moment derivatives with respect to the normal
      coordinates and transition moments were determined for 26 of the 30 fundamentals.
      The total intensities of the in-plane and out-of-plane fundamentals were compared
      to benzene and other monosubstituted benzene derivatives using the F-sum rule. It
      was found that the total intensity of the out-of-plane fundamentals is
      essentially the same for the different compounds while the total intensities for
      the in-plane fundamentals varies according to the electronegativities of the
      substituents.

PMID- 16945576
TI  - Spectral and optical studies of 2-amino-5-nitropyridinium dihydrogen phosphate: a
      semiorganic nonlinear optical material.
AB  - 2-Amino-5-nitropyridinium dihydrogen phosphate (2A5NPDP) was synthesized and the
      molecular structure was elucidated by FT-IR, FT-Raman and FT-NMR. The proton and
      carbon configurations of 2A5NPDP was confirmed through FT-NMR technique. UV-vis
      NIR spectrum was recorded and the optical transmittance region was identified as
      350 nm. Single crystals were grown from ethanol by slow evaporation technique at
      35 degrees C and the unit cell constants were determined. Bulk and powder second
      harmonic generation (SHG) measurements were carried out using Nd:YAG laser
      (lambda=1064 nm) and its phase matching condition was determined.

PMID- 16945577
TI  - A new substrate for surface enhanced Raman scattering of dye Sudan molecules.
AB  - A new SERS substrate was prepared using electro-polishing aluminum foils. Based
      on these high active SERS systems, surface enhanced Raman scattering (SERS) of
      Azo Dye Sudan were performed and carefully studied based on this highly active
      SERS substrate. High quality SERS spectra were obtained, which indicates that
      this kind of coarse aluminum foils is an active SERS substrate. Numbers of
      additional modes were presented, as well as some split peaks, which may be a
      consequence of symmetry lowering.

PMID- 16945578
TI  - Vibrational spectroscopy investigation using ab initio and density functional
      theory analysis on the structure of 3-aminobenzotrifluoride.
AB  - In this work, we will report a combined experimental and theoretical study on
      molecular and vibrational structure of 3-aminobenzotrifluoride. The FT-Raman and
      Fourier transform infrared spectra of 3-aminobenzotrifluoride (3ABTF) were
      recorded in the liquid phase. The equilibrium geometry, harmonic vibrational
      frequencies, infrared intensities and Raman scattering activities, depolarization
      ratios, reduced masses were calculated by HF and density functional B3LYP method
      with the 6-31G(d,p) and 6-311G(d,p) basis sets. The scaled theoretical
      wavenumbers showed very good agreement with the experimental values. The
      thermodynamic functions of the title compound were also performed at HF/6
      31G(d,p)/6-311G(d,p) and B3LYP/6-31G(d,p)/6-311G(d,p) levels of theory. A
      detailed interpretations of the infrared and Raman spectra of 3ABTF is reported.
      The theoretical spectrograms for FT-IR spectra of the title molecule have been
      constructed.

PMID- 16945579
TI  - Vibrational analysis of n-butyl, isobutyl, sec-butyl and tert-butyl nitrite.
AB  - Raman and infrared spectra of n-butyl, isobutyl, sec-butyl and tert-butyl nitrite
      are reported. Density functional theory and Moeller-Plesset calculations with 6
      31G* and 6-311G* basis sets were used to determine ground state molecular
      geometries and vibrational frequencies of these compounds. Calculations and
      spectral data of these molecules were used to perform partial vibrational mode
      assignments for the observed transitions. In agreement with previous
      investigations of alkyl nitrites, cis and trans rotational conformers of n-butyl,
      isobutyl and sec-butyl nitrite were observed in the gas phase infrared spectra
      and the condensed phase Raman and infrared spectra. Among the several predicted
      geometries of these compounds, the cis-trans geometry (cis with respect to the C
      O-N=O dihedral angle and trans with respect to the C-C-O-N dihedral) was
      calculated to be the most stable conformer of n-butyl and isobutyl nitrite, while
      the cis-gauche conformer was found to be the most stable geometry of sec-butyl
      nitrite. The cis-type structures of these three molecules are favored due to
      formation of a pseudo hydrogen bond between the nitrite group and the alpha
      carbon hydrogen atoms. Hindrance with the alkyl moiety, however, causes the trans
      conformer (trans with respect to the C-O-N=O dihedral) of tert-butyl nitrite to
      lie lower than its cis conformer, a result that was supported by our
      spectroscopic measurements. The characteristic N=O stretch frequency for the
      trans conformers of all the compounds examined was observed to decrease with
      increasing branching at the alpha-carbon, while the same mode for the cis
      conformers shows no change among the primary and secondary nitrites. Evidence is
      also provided that suggests that the relative number of cis conformers to trans
      conformers decreases as the alpha-carbon branching increases.

PMID- 16945580
TI  - Synthesis and infrared and fluorescence spectra of rare earth complexes with a
      novel amide-based ligand.
AB  - A novel amide-based open-chain crown ether, N,N'-1,3-propanediyl-bis[2-(benzyl 
      carbamoyl-methoxy)-benzamide] (L) and its solid complexes with rare earth
      nitrates and picrates have been prepared. The complexes were characterized by
      elemental analyses, molar conductivity and IR spectra. The fluorescence
      properties of the Eu(III) and Tb(III) complexes in solid and in organic solvents
      were studied. Under the excitation of ultraviolet light, these complexes exhibit
      characteristic emission of europium and terbium ions. The results show that the
      ligand favor energy transfers to the emitting energy level of Tb(III). Some
      factors that influence the fluorescent intensity were also discussed.

PMID- 16945581
TI  - A novel fluorescent sensor for metal cations and protons based of bis-1,8
      naphthalimide.
AB  - A newly synthesized bis-1,8-naphthalimide aimed to increase its fluorescence
      intensity in the presence of protons or metal cations has been investigated. Its
      spectral photophysical characteristics in acetonitrile and chloroform solutions
      are described. The influence of metal cations (Zn(2+), Ni(2+), Ce(3+), Co(2+),
      Cu(2+) and Ag(+)) and protons on the fluorescence intensity has been investigate
      with regard to obtain fluorescence sensors for this ions in the environment.

PMID- 16945582
TI  - Quantitating the association of charged molecules with ionic micelles.
AB  - We have studied micelles comprised of cationic (CTAB) and anionic (SDS)
      surfactants through the interactions of solution phase anionic disodium
      fluorescein (DSF) and cationic rhodamine 110 (R110) dyes with perylene
      sequestered within the micelles. Fluorescence lifetime measurements monitor
      energy transfer between the nonpolar optical donor within the micelle and ionic
      probes in the surrounding solution. The efficiency of this process is mediated by
      the extent to which the ionic dyes interact with the micelle palisade layer, and
      our fluorescence lifetime data allow us to determine the association constants
      for acceptor-micelle interactions.

PMID- 16945583
TI  - Group V sPLA2: classical and novel functions.
AB  - Group V sPLA(2) is unique among the family of secretory sPLA(2) enzymes in being
      able to bind to cell membranes through both interfacial-binding and through
      binding to proteoglycan. The function of group V sPLA(2) as an enzyme and its
      cross-talk with cPLA(2)alpha in initiating eicosanoid generation is well
      documented. Evidence, though, is emerging on the ability of this molecule to act
      as a regulator of several intracellular and extracellular pathways independently
      of its ability to provide arachidonic acid for eicosanoid generation, acting
      within the cell or as a secreted enzyme. In this article we will provide an
      overview of the properties of the enzyme and how they relate to our current
      understanding of its function.

PMID- 16945584
TI  - Membrane binding and subcellular targeting of C2 domains.
AB  - C2 domains are a ubiquitous structural module and many of them function in Ca2+ 
      dependent membrane binding and thereby serve as Ca2+ effectors for divergent Ca2+
      -mediated cellular processes. Extensive structural, biochemical, biophysical, and
      cellular studies of C2 domains and host proteins in the past decade have shown
      that due to their structural diversity C2 domains have disparate Ca2+
      sensitivity, lipid selectivity and membrane binding mechanisms. This review
      summarizes the basic structural and functional properties of C2 domains as well
      as recent findings on Ca2+ and membrane binding, lipid selectivity, and
      subcellular localization of C2 domains and their host proteins.

PMID- 16945585
TI  - Role of leucine zipper motif in apoE3 N-terminal domain lipid binding activity.
AB  - The N terminal domain of human apolipoprotein E3 (apoE3-NT) functions as a ligand
      for members of the low-density lipoprotein receptor (LDLR) family. Whereas lipid
      free apoE3-NT adopts a stable four-helix bundle conformation, a lipid binding
      induced conformational change is required for LDLR recognition. To investigate
      the role of a leucine zipper motif identified in the helix bundle on lipid
      binding activity, three leucine residues in helix 2 (Leu63, Leu71 and Leu78) were
      replaced by alanine. Recombinant "leucine to alanine" (LA) apoE3-NT was produced
      in E. coli, isolated and characterized. Stability studies revealed a transition
      midpoint of guanidine hydrochloride induced denaturation of 2.7 M and 2.1 M for
      wild type (WT) and LA apoE3-NT, respectively. Results from fluorescent dye
      binding assays revealed that, compared to WT apoE3-NT, LA apoE3-NT has an
      increased content of solvent exposed hydrophobic surfaces. In phospholipid
      vesicle solubilization assays, LA apoE3-NT was more effective than WT apoE3-NT at
      inducing a time-dependent decrease in dimyristoylphosphatidylglycerol vesicle
      light scattering intensity. Likewise, in lipoprotein binding assays, LA apoE3-NT
      protected human low-density lipoprotein from phospholipase C induced aggregation
      to a greater extent than WT apoE3-NT. On the other hand, LA apoE3-NT and WT apoE3
      NT were equivalent in terms of their ability to bind a soluble LDLR fragment. The
      results suggest that the leucine zipper motif confers stability to the apoE3-NT
      helix bundle state and may serve to modulate lipid binding activity of this
      domain and, thereby, influence the conformational transition associated with
      manifestation of LDLR binding activity.

PMID- 16945586
TI  - In vitro testing of platelets using the thromboelastogram, platelet function
      analyzer, and the clot signature analyzer to predict the bleeding time.
AB  - BACKGROUND: Platelet aggregation, thromboxane A2 production and platelet annexin
      V binding are in vitro tests used to assess platelet function. This study was
      done to evaluate the clot signature analyzer (CSA), platelet function analyzer
      (PFA), and thromboelastogram (TE) as in vitro tests to predict the template
      bleeding time (BT). STUDY DESIGN AND METHODS: Twelve normal volunteers were
      studied before and after removal of 2 units of RBC. Seven females were reinfused
      their RBC and 5 males were not. Samples were collected prior to and at 24, 48,
      and 72 h and 7 days after the RBC removal whether or not reinfusion of RBC was
      performed for measurement of TE, CSA, PFA and template BT. RESULTS: BT increased
      significantly following the removal of 2 units of RBC and BT decreased
      significantly after the reinfusion of the 2 units of RBC in the 7 female
      volunteers. BT decreased during the 7-day period in the 5 male volunteers not
      reinfused their RBC. No significant correlations were observed between BT and
      platelet hemostatic time (PHT) and clotting time (CT) in the CSA and between the
      bleeding time and the closure time (CT) in the platelet function analyzer (PFA).
      Significant correlations were observed between BT and K time, the MA, and the
      angle recorded in the thromboelastogram. CONCLUSION: In this study in vitro
      testing using the clot signature analyzer, platelet function analyzer and the
      thromboelastogram could not be used to predict the template bleeding time.

PMID- 16945587
TI  - Dealing with repetitions in sequencing by hybridization.
AB  - DNA sequencing by hybridization (SBH) induces errors in the biochemical
      experiment. Some of them are random and disappear when the experiment is
      repeated. Others are systematic, involving repetitions in the probes of the
      target sequence. A good method for solving SBH problems must deal with both types
      of errors. In this work we propose a new hybrid genetic algorithm for isothermic
      and standard sequencing that incorporates the concept of structured combinations.
      The algorithm is then compared with other methods designed for handling errors
      that arise in standard and isothermic SBH approaches. DNA sequences used for
      testing are taken from GenBank. The set of instances for testing was divided into
      two groups. The first group consisted of sequences containing positive and
      negative errors in the spectrum, at a rate of up to 20%, excluding errors coming
      from repetitions. The second group consisted of sequences containing repeated
      oligonucleotides, and containing additional errors up to 5% added into the
      spectra. Our new method outperforms the best alternative procedures for both data
      sets. Moreover, the method produces solutions exhibiting extremely high degree of
      similarity to the target sequences in the cases without repetitions, which is an
      important outcome for biologists. The spectra prepared from the sequences taken
      from GenBank are available on our website http://bio.cs.put.poznan.pl/.

PMID- 16945588
TI  - Foxp3 controls autoreactive T cell activation through transcriptional regulation
      of early growth response genes and E3 ubiquitin ligase genes, independently of
      thymic selection.
AB  - To elucidate the mechanisms of autoreactive T cell activation and expansion, we
      used endogenous viral superantigens (VSAg)-reactive T cells as a model of self
      antigens in two strains of Foxp3-mutant mice. These two strains, together with
      wild-type mice, provided us with an advantage to simultaneously study the
      positively and negatively selected as well as rescued autoreactive T cells. We
      show here that while both VSAg-reactive and non-VSAg-reactive T cells are equally
      activated in Foxp3-mutant mice, only the VSAg-reactive T cells are preferentially
      expanded independently of their selected states in the thymus. The T cell
      activation appears to be controlled by Foxp3 through transcriptional regulation
      of early growth response (Egr) genes Egr-2 and Egr-3, and E3 ubiquitin (Ub)
      ligase genes Cblb, Itch and GRAIL, subsequently affecting degradation of two key
      signaling proteins, PLCgamma1 and PKC-theta. Physiologically, the positively, but
      not negatively selected VSAg-reactive T cells are spontaneously activated without
      significant expansion. The results suggest that autoreactive T cell activation is
      controlled by Foxp3 through transcriptional regulation of early growth response
      genes and E3 ubiquitin ligase genes, independently of thymic selection.

PMID- 16945589
TI  - Identification, sequencing and expression of selenium-dependent glutathione
      peroxidase transcript in the freshwater bivalve Unio tumidus exposed to Aroclor
      1254.
AB  - Glutathione peroxidases (GPx) and glutathione S-transferases (GST) are essential
      enzymes of the cellular defense system. The aim of this work was the
      identification of GPx transcript in a freshwater bivalve, Unio tumidus, and the
      effects of Aroclor 1254 on GPx and pi-class GST (pi-GST) expression pattern. The
      GPx full-length coding sequence was obtained by reverse transcription PCR using
      degenerated primers followed by 5' and 3' rapid amplification of cDNA ends. The
      GPx cDNA encodes a protein of 232 amino acids. The 72nd amino acid corresponds to
      a selenocysteine encoded by a TGA codon. Residues essential to the enzymatic
      function are conserved in GPx of U. tumidus. Specific amplifications of the Se
      GPx mRNA from U. tumidus were performed on the digestive gland, the excretory
      system and the gills. Se-GPx expression level is highest in the digestive gland.
      No induction of the Se-GPx was observed at the transcriptional level in the
      digestive gland and the excretory system of Aroclor-treated mussels, while an
      increase of the pi-GST mRNA level was observed in the excretory system.

PMID- 16945590
TI  - Neurokinin3 receptor regulation of the airways.
AB  - Neurokinin(3) (NK(3)) receptors may regulate the airways primarily through
      actions on the nerves. In the periphery, airway parasympathetic ganglia neurons
      are depolarized following NK(3) receptor activation resulting subsequently in the
      facilitation of synaptic transmission. Such an effect may account for the
      excessive parasympathetic reflex effects (e.g. airway smooth muscle contraction,
      vascular engorgement, mucus secretion) associated with asthma and chronic
      obstructive pulmonary disease (COPD). In the central nervous system (CNS), NK(3)
      receptor activation may regulate airway vagal afferent relay neurons, rendering
      them hyperresponsive to parallel inputs from glutamate containing afferent
      nerves. This process is analogous to the process of central sensitization
      regulating hyperalgesia and pain in somatic tissues. In both the CNS and in the
      airways, NK(3) receptors are likely activated by either substance P and/or
      neurokinin A (NKA), both of which are full agonists at NK(3) receptors, as there
      is little evidence that airway nerves express neurokinin B (NKB). Evidence for
      other potential sites of regulation by NK(3) receptors in the airways (e.g.
      vasculature, airway smooth muscle, epithelium, mucus glands) is either
      inconclusive or conflicting.

PMID- 16945591
TI  - New-onset diabetes and pancreatic cancer.
AB  - BACKGROUND & AIMS: Although many individuals with pancreatic cancer have
      diabetes, the association between new-onset diabetes mellitus and the subsequent
      incidence of pancreatic cancer is unclear. METHODS: We conducted a retrospective
      cohort study to estimate the incidence of pancreatic cancer subsequent to a new
      diabetes diagnosis and to evaluate factors associated with a subsequent
      pancreatic cancer diagnosis. We used the Veterans Health Administration National
      Patient Care Database to assemble a cohort of 1,421,794 US veterans without prior
      diabetes or pancreatic cancer diagnoses. We recorded coding for new diabetes
      diagnoses (> or =2 International Classification of Diseases-9 codes for diabetes
      within a 12-month period), pancreatic cancer, age, sex, race, and common
      gastrointestinal symptoms. RESULTS: A total of 36,631 (2.6%) of the 1,421,794
      veterans were diagnosed with new-onset diabetes in 1999; 149 subsequently
      received a diagnosis of pancreatic cancer. Pancreatic cancer incidence in
      patients with new-onset diabetes (83.8/100,000 person-years) was 2.2-fold higher
      (95% confidence interval, 1.84-2.56) than in nondiabetics, and was highest during
      the first 2 years after diabetes diagnosis. One additional pancreatic cancer was
      diagnosed for every 332 new diabetics over 6 years. A subsequent pancreatic
      cancer diagnosis (among new-onset diabetics) was associated independently with
      younger age groups, changes in bowel habits, constipation, epigastric pain, and
      malnutrition. CONCLUSIONS: New-onset diabetes was associated with a significantly
      increased rate of pancreatic cancer diagnosis, particularly in the first 2 years
      after diabetes diagnosis. Factors associated with pancreatic cancer diagnosis
      included younger age groups and the presence of gastrointestinal symptoms. The
      absolute incidence of pancreatic cancer was low.

PMID- 16945592
TI  - Nausea and vomiting--an interdisciplinary approach.

PMID- 16945593
TI  - Functional cortical imaging of nausea and vomiting: a possible approach.
AB  - From a naive point of view, a study on functional cortical imaging of nausea and
      vomiting should deliver insight into the basic cortical mechanisms, connections,
      and time courses, of nausea and vomiting as perceived and processed in the human
      brain of affected subjects. Until now the brain's response to nausea and vomiting
      are only inadequately characterized, because studies have been focused mostly on
      understanding the different mechanisms leading to nausea rather than to cortical
      activations during nausea or vomiting, respectively. Consequently, the imaging of
      the "personal experience" of nausea and vomiting can currently be regarded as
      terra incognita. Nonetheless, the wide variety of the results published on
      diverse aspects of the topic can be helpful in providing guidelines for a
      paradigm to further investigations. This paper presents a brief outline for a
      study on the functional imaging of nauseated humans by means of functional
      magnetic resonance imaging (fMRI).

PMID- 16945594
TI  - Endocrine correlates of acute nausea and vomiting.
AB  - This paper gives an overview of studies investigating endocrine changes in acute
      nausea and vomiting. The aetiology of nausea and vomiting is not fully
      understood, but it has been shown that different stress hormones are released
      into circulation during motion sickness. Studies with animals and humans have
      shown that acute nausea activates the hypothalamo-pituitary-adrenal axis and the
      neurohypophyseal system. So-called stress hormones, like adrenocorticotropic
      hormone, cortisol, and antidiuretic hormone, are released concomitant with nausea
      and vomiting in motion sickness, but do not seem to be involved in the aetiology
      of motion sickness. Nevertheless, plasma levels of stress hormones more or less
      correlate to the intensity of nausea related symptoms. Although
      gastroenteropancreatic hormones are involved in gastrointestinal motility, there
      are only few data describing their changes in response to acute nausea or
      vomiting.

PMID- 16945595
TI  - A hemagglutinin with mitogenic activity from dark red kidney beans.
AB  - A 67-kDa hemagglutinin composed of two identical subunits was purified from
      Phaseolus vulgaris cv. 'Dark Red Kidney Bean'. It was unadsorbed on DEAE
      cellulose but adsorbed on Affi-gel blue gel. The hemagglutinin was highly
      purified after the two aforementioned chromatographic steps as revealed by a
      single peak in gel filtration on Superdex 75 and a single band in SDS-PAGE. The
      hemagglutinating activity was stable between 25 degrees C and 70 degrees C, and
      between pH 4 and pH 11, and in the presence of a variety of divalent metal
      chlorides at 500 mM concentration. The activity was reduced by 50% at 80 degrees
      C, and also when the pH was lowered to 3 or elevated to 12. The activity was
      reduced by 75% in the presence of 250 mM KCl or NaCl. A variety of sugars tested
      failed to inhibit the hemagglutinating activity of the hemagglutinin. Although
      the hemagglutinin exhibited mitogenic activity toward murine splenocytes, it had
      no effect on the activity of HIV-1 reverse transcriptase or mycelial growth in
      the fungi Botrytis cinerea, Fusarium oxysporum and Mycosphaerella arachidicola.
      It exerted an antiproliferative activity on leukemia L1210 cells.

PMID- 16945596
TI  - A method for the identification of glycoproteins from human serum by a
      combination of lectin affinity chromatography along with anion exchange and Cu
      IMAC selection of tryptic peptides.
AB  - This paper reports a method for identifying glycoproteins from human serum.
      Glycoproteins were selected with a concanavalin A (Con A) lectin column and then
      tryptically digested prior to sequential chromatographic selection of acidic and
      histidine containing peptides. Acidic peptides were selected with a strong anion
      exchange (SAX) column. Peptides captured by the SAX columns were then released
      and histidine-containing peptides in the mixture selected with a copper loaded
      immobilized metal affinity chromatography (Cu-IMAC) column. This serial
      chromatographic selection process reduced the complexity of proteolytic digests
      by more than an order of magnitude. Peptides selected by this serial process were
      then fractionated by reversed-phase chromatography (RPC) and identified by tandem
      mass spectrometry. The method was initially validated using human transferrin
      before application to human serum. The results show that all the peptides
      identified except one contained histidine and acidic amino acids.

PMID- 16945597
TI  - Characterization of Human gamma-glutamyl hydrolase in solution demonstrates that
      the enzyme is a non-dissociating homodimer.
AB  - Human gamma-glutamyl hydrolase (hGH) is a key enzyme in the metabolism of folic
      acid and in the pharmacology of many antifolate drugs. hGH catalyzes removal of
      the poly-gamma-glutamate chains of intracellular folic acid and antifolates. hGH
      crystallized as a homodimer with two putative active sites. However, the
      quaternary structure and the number of species of the enzyme in solution have not
      been determined. hGH has now been characterized using analytical
      ultracentrifugation and dynamic light scattering. HisTag fusion proteins of wild
      type hGH, rat GH, and hGH expressed as a glycosylated protein were studied.
      Analyses of HisTag wild-type hGH were conducted over a range of protein
      concentrations (1.4-200 microM), ionic strengths (0-1 M NaCl), and pH (4.5-8.5).
      A single species with a molecular mass consistent with a homodimer was observed.
      Glycosylated hGH and HisTag rat gamma-glutamyl hydrolase also formed very stable
      homodimers. The lack of dissociation of the dimer, the large monomer-monomer
      interface, and the presence of catalytically essential Tyr-36 in the homodimer
      interface sequences suggest that homodimer formation is required for the hGH
      monomer to fold into an active conformation. The conservation of hGH monomer
      monomer interface sequences in other mammalian and plant gamma-glutamyl hydrolase
      molecules suggests that they also exist as stable homodimers.

PMID- 16945598
TI  - Pharmacodynamic studies on PPIs: look carefully at the country of origin.

PMID- 16945599
TI  - Pegylated interferon (PEG-IFN) alfa-2b and ribavirin for recurrent hepatitis C
      (genotype 1) after liver transplantation: relationship with steatosis.

PMID- 16945600
TI  - Simulation of discontinuous damage incorporating residual stresses in
      circumferentially overstretched atherosclerotic arteries.
AB  - When a balloon-angioplasty is performed, the arterial wall is overstretched and
      thereby damaged, which leads to a stiffness reduction in the arterial layers. An
      anisotropic damage model able to reflect the main damage mechanisms in
      overstretched arterial walls is used in combination with a polyconvex
      hyperelastic stored energy function. Furthermore, a method for the incorporation
      of residual stresses present in the wall of unloaded configurations is applied.
      The energy describes the anisotropic hyperelastic behavior of arteries under
      physiological conditions. Due to the assumption that the rupture of cross-bridges
      between collageneous micro-fibrils is responsible for the damage inside arterial
      walls, the damage function is applied to that part of the energy only which is
      associated to the fiber elasticity. For the incorporation of the residual
      stresses into the simulation, we apply a method which consists of two simulation
      steps. Finally, a numerical simulation of the overstretching of a simplified
      atherosclerotic artery is performed taking into account residual stresses.

PMID- 16945601
TI  - What diet should we recommend to patients?

PMID- 16945602
TI  - The body in the dissection lab: thing or taboo?

PMID- 16945603
TI  - Selective serotonin reuptake inhibitors and risk of upper GI bleeding: confusion
      or confounding?
AB  - BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) represent a
      relatively new class of antidepressants. Several studies have reported bleeding
      disorders associated with the use of SSRIs, which are considered the result of a
      decrease in platelet serotonin leading to a defect in platelet aggregation. To
      what extent the use of SSRIs increases the risk of gastrointestinal bleeding is
      unclear. METHODS: A comprehensive literature search for studies addressing SSRI
      use and upper gastrointestinal tract bleeding (UGIB) was conducted using Medline,
      EMBASE, and Cochrane databases with a recursive manual reference search up to May
      2005. Any observational and interventional studies were systematically reviewed,
      and critical appraisal was conducted on available studies. RESULTS: Published
      clinical evidence on the relationship between SSRI use and gastrointestinal
      bleeding is limited to observational studies without any clinical trials. Three
      cohort studies and one case-control study met inclusion criteria. These studies
      combined different affinity SSRIs in the class and had differing control groups
      with conflicting conclusions. Both a cohort study and a case-control study
      investigating the concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs)
      or low-dose aspirin found that combined use with an SSRI increased the risk of
      UGIB. CONCLUSIONS: Only a few epidemiology studies have investigated the
      association between SSRIs and UGIB. They provide weak evidence to support the
      hypothesis of a link between SSRIs and UGIB at a population level. Available
      evidence shows that concurrent use of NSAIDs or aspirin with SSRIs greatly
      increases the risk of UGIB. The preventive strategy should be considered in those
      SSRI users at high risk, especially the elderly or those with a history of UGIB
      and taking nonselective NSAIDs or aspirin.

PMID- 16945604
TI  - Screening for colorectal cancer in average-risk populations.
AB  - Screening average-risk populations for colorectal cancer can reduce the incidence
      and mortality of colorectal cancer. Effectiveness depends on programmatic
      adherence and quality. This review discusses the evidence supporting the use of
      currently available screening tests. The discussion specifically focuses on
      programmatic issues and highlights the importance of quality assurance in each
      program.

PMID- 16945605
TI  - Constipation in the primary care setting: current concepts and misconceptions.
AB  - Constipation is prevalent in Western societies and is a common illness in
      clinical practice. A broader clinical definition, which encompasses difficult and
      infrequent defecation, has aligned medical concepts with that of patients and the
      general population. Unfortunately, there are widespread misconceptions concerning
      the origins and management of constipation within both the lay and medical
      communities that influence recommendations by health care practitioners. This
      review highlights and seeks to correct some of these misconceptions and provide
      treatment guidelines for the practicing physician.

PMID- 16945606
TI  - High pressure surgery.

PMID- 16945607
TI  - Red spots and recurrent anemia.

PMID- 16945608
TI  - Inverted U waves.

PMID- 16945609
TI  - An odd case of hypertension.

PMID- 16945610
TI  - Fruit and vegetable juices and Alzheimer's disease: the Kame Project.
AB  - BACKGROUND: Growing evidence suggests that oxidative damage caused by the beta
      amyloid peptide in the pathogenesis of Alzheimer's disease may be hydrogen
      peroxide mediated. Many polyphenols, the most abundant dietary antioxidants,
      possess stronger neuroprotection against hydrogen peroxide than antioxidant
      vitamins. METHODS: We tested whether consumption of fruit and vegetable juices,
      containing a high concentration of polyphenols, decreases the risk of incident
      probable Alzheimer's disease in the Kame Project cohort, a population-based
      prospective study of 1836 Japanese Americans in King County, Washington, who were
      dementia-free at baseline (1992-1994) and were followed through 2001. RESULTS:
      After adjustment for potential confounders, the hazard ratio for probable
      Alzheimer's disease was 0.24 (95% confidence interval [CI], 0.09-0.61) comparing
      subjects who drank juices at least 3 times per week with those who drank less
      often than once per week with a hazard ratio of 0.84 (95% CI, 0.31-2.29) for
      those drinking juices 1 to 2 times per week (P for trend < .01). This inverse
      association tended to be more pronounced among those with an apolipoprotein
      Eepsilon-4 allele and those who were not physically active. Conversely, no
      association was observed for dietary intake of vitamins E, C, or beta-carotene or
      tea consumption. CONCLUSIONS: Fruit and vegetable juices may play an important
      role in delaying the onset of Alzheimer's disease, particularly among those who
      are at high risk for the disease. These results may lead to a new avenue of
      inquiry in the prevention of Alzheimer's disease.

PMID- 16945611
TI  - Fruit and vegetable consumption and risk of cholecystectomy in women.
AB  - PURPOSE: Many constituents of fruits and vegetables may reduce the risk for
      gallstones, but prospective data relating fruit and vegetable intake to gallstone
      disease are sparse. METHODS: We prospectively studied fruit and vegetable
      consumption in relation to the risk of cholecystectomy in a cohort of 77,090
      women in the Nurses' Health Study, 37 to 64 years of age, who had no history of
      gallstone disease. Women reported on follow-up questionnaires both their
      consumption of fruits and vegetables and whether they had undergone
      cholecystectomy. RESULTS: During 1,060,033 person-years of follow-up from 1984 to
      2000, participants reported 6608 cases of cholecystectomy. After adjusting for
      established or suspected risk factors, the relative risk for women in the highest
      quintile of overall consumption of fruits and vegetables was 0.79 (95% confidence
      interval [CI], 0.73-0.87, P for trend<.0001) compared with those in the lowest
      quintile. Similar results were seen for both total fruits and total vegetables
      separately. The composite items of fruits and vegetables including green leafy
      vegetables, citrus fruits, vitamin C-rich fruits and vegetables, and cruciferous
      vegetables also were each inversely associated with the risk. CONCLUSIONS: Our
      findings suggest a protective role of greater fruit and vegetable consumption
      against risk of cholecystectomy in women.

PMID- 16945612
TI  - Laryngeal cancer and gastroesophageal reflux disease: a case-control study.
AB  - PURPOSE: Gastroesophageal reflux disease (GERD) is common in patients with
      laryngeal cancer. However, the role of GERD in laryngeal cancer remains
      controversial because of poor matching and selection of inappropriate control
      groups in prior studies. We aimed to better understand this relationship by
      conducting a matched case-control study. METHODS: This study was based in a
      single tertiary care center over a 2-year period. Cases included all patients
      with a diagnosis of new laryngeal cancer presenting to the otolaryngology
      clinics. Two controls, derived from the internal medicine clinics, were matched
      to the cases on an individual basis for age (within 1 year), gender, ethnicity,
      and time of first visit to the institution (within 1 month). Data were extracted
      by chart review. Conditional logistic regression was used to assess the
      relationship between laryngeal cancer and GERD, tobacco, and alcohol consumption.
      RESULTS: A total of 96 cases were matched to 192 controls. On univariable
      analysis, the significant risk factors were current smoking, odds ratio (OR) 5.46
      (95% confidence interval [CI], 2.59-11.50); alcohol, OR 1.97 (CI, 1.19-3.26); and
      GERD, OR 1.79 (CI, 1.03-3.11). On multivariable analysis, only smoking and GERD
      continued to be significantly associated with laryngeal cancer, OR 6.08 (CI, 2.82
      13.10) and OR 2.11 (CI, 1.16-3.85), respectively. CONCLUSIONS: Smoking and GERD
      are significant risk factors for laryngeal cancer and may have an independent
      incremental risk for laryngeal carcinogenesis.

PMID- 16945613
TI  - Randomized controlled trial of calcium in healthy older women.
AB  - PURPOSE: Calcium has been shown to have positive effects on bone mineral density
      in postmenopausal women. However, these effects are small, it is unknown whether
      they are sustained with long-term use, they have not been shown with intention-to
      treat analyses, and the evidence for fracture prevention with calcium monotherapy
      is inconsistent. METHODS: A randomized controlled trial of calcium (1 g/day as
      the citrate) in 1471 healthy postmenopausal women (aged 74+/-4 years) was
      performed to assess the effects on bone density and fracture incidence over 5
      years. RESULTS: Follow-up was complete in 90% of subjects, and average medication
      compliance was 55% to 58%. Calcium had a significant beneficial effect on bone
      density (intention-to-treat analysis), with between-groups differences at 5 years
      of 1.8% (spine), 1.6% (total hip), and 1.2% (total body). Effects were greater in
      a per-protocol analysis (5-year differences of 2.3%, 2.8%, and 1.8%,
      respectively). A total of 425 fractures occurred in 281 women. Hazard ratios,
      based on time to first fracture, were 0.90 (95% confidence interval [CI], 0.71
      1.16) for any symptomatic fracture, 0.72 (95% CI, 0.44-1.18) for vertebral, 3.55
      (95% CI, 1.31-9.63) for hip, and 0.65 (95% CI, 0.41-1.04) for forearm fracture.
      Per-protocol analysis found respective hazard ratios of 0.86 (95% CI, 0.64-1.17),
      0.62 (95% CI, 0.33-1.16), 3.24 (95% CI, 0.65-16.1), and 0.45 (95% CI, 0.24-0.87).
      Height loss was reduced by calcium in the per-protocol population (P=.03). Serum
      alkaline phosphatase and procollagen type-I N-terminal propeptide were lower in
      the calcium group at 5 years, but constipation was more common. CONCLUSIONS:
      Calcium results in a sustained reduction in bone loss and turnover, but its
      effect on fracture remains uncertain. Poor long-term compliance limits its
      effectiveness.

PMID- 16945614
TI  - Change in lipid profile in celiac disease: beneficial effect of gluten-free diet.
AB  - PURPOSE: Celiac disease is associated with hypocholesterolemia, which is thought
      to contribute to a favorable cardiovascular risk profile. This led to suggestions
      that the diagnosis of celiac disease and its treatment with a gluten-free diet
      may result in elevation of the serum cholesterol level and worsen this risk
      profile. However, no study proves this in adults. We therefore examined the
      effect of a gluten-free diet on the lipid profile in patients with celiac
      disease. SUBJECTS AND METHODS: We identified 132 patients with celiac disease who
      adhered to a gluten-free diet and had lipid profiles performed before and after a
      median of 20.5 months on the diet. The patients lacked diseases that may affect
      serum lipids. RESULTS: There were significant increases in total cholesterol and
      high-density lipoprotein (HDL) cholesterol (P < .0001) but not low-density
      lipoprotein (LDL) cholesterol (P=.06). The LDL/HDL ratio decreased by 0.36+/-0.7
      (P < .0001). Both men and women had a significant increase in total cholesterol
      and HDL and a significant decrease in the LDL/HDL ratio. Only men had increases
      in LDL (P=.02). The greatest increase in lipid values was seen in those with the
      lowest initial values. The largest increase in HDL was seen in subjects with more
      severe disease as indicated by low albumin level and presence of total villous
      atrophy. CONCLUSIONS: Diagnosis of celiac disease and its treatment with a gluten
      free diet resulted in improvement in the lipoprotein profile, which included an
      increase in HDL and a decrease in the LDL/HDL ratio.

PMID- 16945615
TI  - Prospective comparison of patient experience with colon imaging tests.
AB  - PURPOSE: Patient experience varies with the currently available colon imaging
      tests, including air contrast barium enema, computed tomographic colonography,
      and colonoscopy. We examined differences in patient experience with colon imaging
      tests and whether they varied with gender, age, and race. SUBJECTS AND METHODS:
      Patients with fecal occult blood, hematochezia, iron-deficiency anemia, or a
      family history of colon cancer underwent air contrast barium enema followed 7 to
      14 days later by computed tomographic colonography and colonoscopy. Validated
      patient experience questionnaires that measured the experience for each test and
      a separate questionnaire that obtained an overall summary measure were
      administered after testing. Eleven patient experiences including pain,
      embarrassment, difficulty with bowel preparation, and satisfaction with tests
      were examined. RESULTS: A total of 614 subjects completed all 3 imaging tests.
      The test most patients were willing to repeat was colonoscopy; it also was
      reported to be the least painful procedure. Patients were least satisfied with
      air contrast barium enema, and fewer would undergo air contrast barium enema
      compared with computed tomographic colonography or colonoscopy. There were
      limited racial and gender differences in perceptions of the tests. Younger adults
      perceived air contrast barium enema to be more painful than older adults.
      CONCLUSION: Taking into account a wide variety of patient experience measures,
      patients preferred colonoscopy to air contrast barium enema and computed
      tomographic colonography. This finding has important implications for physicians
      considering different colon imaging tests.

PMID- 16945616
TI  - Quality of reporting of randomized controlled trials of herbal medicine
      interventions.
AB  - BACKGROUND: Public interest in herbal medicines has generated an increasing
      number of trials evaluating their efficacy. Trials with poor methodologic quality
      have exaggerated estimates of treatment effect, and incomplete reporting of
      trials causes difficulties in assessing trial methodologic quality. The objective
      of this project was to examine the quality of reporting of randomized controlled
      intervention trials of herbal medicine. METHODS: MEDLINE (1966 to September 2003)
      was searched for randomized controlled trials of 10 herbal medicines. Two
      individuals (J. G. and J. D.) independently assessed trials using the
      Consolidated Standard of Reporting Trials checklist. Disagreements were resolved
      by consensus. The mean number of checklist items reported across all and for
      individual herbal medicines was calculated. The influence of decade of
      publication and species of herbal medicine tested was explored using an analysis
      of variance. RESULTS: A total of 206 randomized controlled trials of herbal
      medicine were included. Interrater reliability on reporting quality assessment
      was high. A total of 45% of items were reported across all trials. The quality of
      reporting improved across decades from the 1970s to the 2000s. Individual herbal
      species differed in the total number of items reported, with echinacea, ginkgo,
      St. John's wort, and kava trials reporting the most items. CONCLUSIONS: Important
      methodologic components of randomized controlled trials of herbal medicines are
      incompletely reported including allocation concealment, method used to generate
      the allocation sequence, and whether an intention-to-treat analysis was used.
      Also, key information unique to these trials may be missing, such as percentage
      of active constituents and type or form of the herbal medicine preparation. We
      suggest trialists consult a recent extension of the Consolidated Standard of
      Reporting Trials statement specific to herbal medicine trials when designing and
      reporting randomized controlled intervention trials of herbal medicines.

PMID- 16945617
TI  - Alcohol consumption as a trigger of recurrent gout attacks.
AB  - BACKGROUND: Alcohol consumption has long been considered a trigger for recurrent
      gout attacks; however, this hypothesis has not been formally tested. METHODS: We
      conducted an Internet-based case-crossover study to assess several putative risk
      factors, including alcohol consumption, thought to trigger recurrent gout
      attacks. Subjects who had an attack within the past year were recruited online
      and asked to provide access to medical records pertaining to their gout. Data
      were obtained on the amount and type of alcoholic beverage consumed on each day
      over the 2-day period before a gout attack and on each day over a 2-day period
      during the intercritical period. We examined the amount and type of alcohol
      consumption and the risk of recurrent gout attacks using a conditional logistic
      regression adjusting for diuretic use and purine intake. RESULTS: A total of 197
      subjects were recruited online over a 10-month period. Of those, 179 (91%)
      fulfilled the American College of Rheumatology Criteria for gout. Compared with
      no alcohol consumption, odds ratios for recurrent gout attacks were 1.1, 0.9,
      2.0, and 2.5 for 1 to 2, 3 to 4, 5 to 6, and 7 or more drinks consumed over the 2
      day period, respectively (P<.005). A dose-response relationship of risk of gout
      attacks was more evident for alcohol consumed over the last 24 hours. An
      increased risk of recurrent gout attacks was found for each type of beverage
      consumed. CONCLUSION: Alcohol consumption triggers recurrent gout attacks. This
      effect was likely to occur within 24 hours after its consumption.

PMID- 16945618
TI  - Open-label study of hemin for acute porphyria: clinical practice implications.
AB  - BACKGROUND: The acute porphyrias are rare inherited diseases characterized by
      acute episodes of life-threatening symptoms. Hemin was approved for treating
      these disorders in 1983. This open-label study of hemin therapy, conducted to
      demonstrate the safety of hemin manufactured in a new facility, is the largest to
      date and provides an overview of the use of hemin in clinical practice in the
      United States. METHODS: During 8 months when hemin was available only through
      study participation, 130 patients with a clinical diagnosis of acute porphyria
      received hemin as regularly prescribed by their doctor. Laboratory information
      and data on use of hemin for acute and prophylactic treatment were analyzed from
      case report forms. RESULTS: Hemin was administered to 111 patients for treatment
      of 305 acute attacks and to 40 patients for prophylaxis (usually by weekly or
      biweekly infusions). Diagnostic laboratory findings reported for 69 patients were
      confirmatory in only 26. Hemin was regarded as effective for all attacks in 73%
      of patients. Doses for acute attacks were less than the recommended 3-4 mg/kg/day
      in 20% of patients. Among 31 patients who received hemin prophylaxis for >1
      month, 68% did not require subsequent hemin treatment for acute attacks. Most
      adverse events were attributed to porphyria and not treatment, and were more
      common in patients treated for acute attacks rather than prophylaxis.
      CONCLUSIONS: Safety and perceived efficacy of hemin were consistent with previous
      studies. Physician education is needed regarding use of diagnostic tests and
      recommended dosing. Preventive regimens are common and deserve further study.

PMID- 16945619
TI  - Artificially sweetened versus regular mixers increase gastric emptying and
      alcohol absorption.
AB  - BACKGROUND: Mixed alcoholic drinks are increasingly being consumed in "diet"
      varieties, which could potentially empty more rapidly from the stomach and
      thereby increase the rate of alcohol absorption when compared with "regular"
      versions containing sugar. METHODS: We studied 8 healthy males twice in
      randomized order. On each day, they consumed an orange-flavored vodka beverage
      (30 g ethanol in 600 mL), made with either "regular" mixer containing sucrose
      (total 478 kcal), or "diet" mixer (225 kcal). RESULTS: Gastric half-emptying time
      measured by ultrasound (mean+/-standard deviation) was less for the "diet" than
      the "regular" drink (21.1+/-9.5 vs 36.3+/-15.3 minutes, P <.01). Both the peak
      blood ethanol concentration (0.053+/-0.006 vs 0.034+/-0.008 g%, P <.001) and the
      area under the blood ethanol concentration curve between 0 and 180 minutes (5.2+/
      0.7 vs 3.2+/-0.7 units, P <.001) were greater with the "diet" drink. CONCLUSIONS:
      Substitution of artificial sweeteners for sucrose in mixed alcoholic beverages
      may have a marked effect on the rate of gastric emptying and the blood alcohol
      response.

PMID- 16945620
TI  - Globalization: a new dimension for academic internal medicine.

PMID- 16945625
TI  - Proceedings of the European Society of Paediatric Urology and the American
      Academy of Pediatrics Section on Urology Joint Meeting, Uppsala, Sweden, June 15
      18, 2005.

PMID- 16945626
TI  - Pediatric urology medal. R. Dixon Walker.

PMID- 16945627
TI  - Global gene expression patterns in mouse wolffian duct development.
AB  - PURPOSE: We identified genes responsible for terminal differentiation of the
      mouse ureter. MATERIALS AND METHODS: We isolated the wolffian ducts of Black
      Swiss mice from embryonic days 12.5 to 14.5. These ducts were processed for total
      RNA extraction. RNA was amplified and converted to biotinylated cDNA, which was
      hybridized to Affymetrix(R) mouse 430 microarray GeneChips. Data were analyzed
      using Affymetrix software provided by the core facility at our institution. Data
      were confirmed by semiquantitative polymerase chain reaction and
      immunohistochemistry. RESULTS: Of 42,000 evaluable transcripts 412 were up
      regulated and 133 were down-regulated more than 1.5-fold between embryonic days
      12.5 and 14.5. Of up-regulated genes 17 were up-regulated more than 3-fold. Of
      these genes 5 were selected for further study and they were identified as having
      roles in cell growth/regulation in general. Increased expression of Foxa1 was
      seen at embryonic day 14.5 in the distal ureter and urogenital sinus.
      CONCLUSIONS: To our knowledge this is the first report of differential gene
      expression patterns in the developing mouse wolffian duct. Our results diverge
      from expression patterns reported in the kidney. This information will enable
      future comparisons between WT and transgenic mice with an abnormal phenotype.

PMID- 16945628
TI  - Bladder augmentation with acellular dermal biomatrix in a diseased animal model.
AB  - PURPOSE: The use of bowel for bladder augmentation is associated with many
      complications. We have reported that acellular dermal biomatrix can be used
      successfully for directing the regeneration of each key bladder wall element in
      healthy domestic pigs. Before proposing that this material should be used in the
      human setting a final set of experiments using this scaffold to replace diseased
      bladder wall is necessary. We determined if acellular dermal biomatrix can be
      used to replace diseased bladder wall. We compared our findings to our previous
      results. MATERIALS AND METHODS: Six domestic male pigs underwent urethral
      ligation and suprapubic tube placement. Five female pigs served as controls for
      bladder dynamics. Machined resistance valves of 5 and 10 cm H(2)O pressure were
      placed into the lumen of the cystostomy catheter for a mean of 3.3 weeks (range 3
      to 4). Obstruction was then relieved and partial cystectomy was performed,
      followed by augmentation with a 4 x 4 cm segment of acellular dermal biomatrix of
      the markedly thickened and poorly compliant bladder. Animals were sacrificed 3
      months following augmentation. Standard urodynamic studies were performed.
      Contractility and compliance were measured in freshly isolated regenerated and
      native bladder tissues. Histological evaluation was performed on hematoxylin and
      eosin, and Masson's trichrome stained sections. RESULTS: Bladder compliance was
      markedly decreased after 3.3 weeks of obstruction. Mean compliance +/- SEM before
      obstruction was 16.28 +/- 9.21 cm H(2)O. After 3.3 weeks of obstruction average
      compliance was 4.13 +/- 0.98 cm H(2)O. One pig died 2 weeks following
      augmentation due to graft separation and sepsis. Gross examination of augmented
      bladders revealed the complete replacement of acellular dermal biomatrix with
      bladder tissue. Histological evaluation revealed extensive fibrosis with small
      islands of poorly organized muscle in contrast to the complete regeneration of
      mucosa, smooth muscle and serosa seen in augmentations previously performed in
      healthy animal bladders. Maximum contractile tension of the patch tissue was not
      different than that in the native tissue from the obstructed hypertrophied
      bladder but it was only approximately 10% of the tension produced by healthy
      tissue from nonobstructed augmented bladders. The obstructed bladder patch and
      native tissue was approximately 14 times stiffer than healthy bladder tissue.
      CONCLUSIONS: While augmentation of healthy porcine bladder with acellular dermal
      biomatrix results in excellent functional bladder tissue regeneration, similar
      experiments in a porcine model of obstructed bladder disease failed to show
      favorable results. Therefore, acellular dermal biomatrix cannot be recommended at
      this time for human bladder dysfunction. Results support the contention that
      matrices designed for human bladder augmentation should be tested in a disease
      animal model before recommending them for human bladder dysfunction.

PMID- 16945629
TI  - Total continence reconstruction: a comparison to staged reconstruction of
      neuropathic bowel and bladder.
AB  - PURPOSE: Surgical treatment for neuropathic bowel and bladder has become an
      essential tool in maximizing the quality of life in patients with
      myelomeningocele. We present our results comparing results in patients who
      underwent total continence reconstruction of the urinary and gastrointestinal
      tracts to patients who underwent a separate or single operation. MATERIALS AND
      METHODS: We performed a retrospective chart review of all patients with
      myelomeningocele at our institution who underwent reconstruction with a cutaneous
      catheterizable urinary channel or Malone antegrade continence enema. We compared
      outcomes with regard to surgical revisions of the channel between patients who
      underwent the construction of each simultaneously, that is total continence
      reconstruction, to outcomes in those with a single channel or who underwent
      reconstruction at 2 or more operations. RESULTS: Most of our patients underwent
      genitourinary and gastrointestinal reconstruction, and few desired surgical
      intervention for only a single system. We were unable to find any differences in
      the continence rate or stomal complications. However, patients who underwent
      staged reconstruction usually had significant secondary reasons for repeat
      surgery. CONCLUSIONS: Surgical success for urinary and fecal continence can be
      safely and effectively achieved through single or multiple procedures. However,
      because of shared pathophysiology, we believe that most patients benefit from
      intervention in the gastrointestinal and the genitourinary tract. Therefore, a
      major advantage of total continence reconstruction is avoidance of the morbidity
      of a second major surgical procedure.

PMID- 16945630
TI  - Augmentation cystoplasty rates at children's hospitals in the United States: a
      pediatric health information system database study.
AB  - PURPOSE: We identified augmentation cystoplasty rates in children with spina
      bifida at children's hospitals enrolled in the Pediatric Health Information
      System database. MATERIALS AND METHODS: The Pediatric Health Information System
      database tabulates demographic and diagnostic patient data from 35 children's
      hospital centers in the United States. Between October 1999 and September 2004 we
      extracted data on 0 to 19-year-old patients with International Classification of
      Diseases-9 diagnosis codes for spina bifida. The International Classification of
      Diseases-9 procedure code for augmentation cystoplasty was cross-referenced with
      these patients to determine the total number of patients with augmentation, total
      population augmentation rates and individual institution rates of bladder
      augmentation. RESULTS: Staff at enrolled pediatric medical centers submitted
      inpatient data accounting for 9,059 beds servicing an aggregate metropolitan
      population of 82 million individuals. In the 5-year period 12,925 unique spina
      bifida patient encounters were identified, including 665 patients who underwent
      augmentation cystoplasty. The mean 5-year institutional number of augmentations
      performed in children with spina bifida was 20 (range 1 to 121) and the mean
      annual number of augmentations performed per institution was 4. The overall
      augmentation rate at 33 hospitals contributing data for the full years 2000 to
      2003 was 5.4% (range 0.5% to 16.3%, p <0.0001). The male-to-female ratio of those
      who underwent augmentation was 1:1.2. Median length of stay in children with
      augmentation was 7 days (mean 9). The median age of children with augmentation
      was 10.4 years, that is 11.3 years in boys and 9.8 years in girls. The difference
      in mean age was statistically significant (p <0.003). At institutions where 10 or
      more augmentations were performed in 5 years (mean 27) mean patient age at
      operation was 10.1 years. This was significantly younger than the mean patient
      age of 12.3 years at hospitals where fewer than 10 augmentations (mean 5) were
      done in 5 years (p <0.05). CONCLUSIONS: Clinical management for neurogenic
      bladder conditions has evolved to emphasize nonoperative management. Several
      studies suggest that aggressive early intervention improves bladder compliance
      and may protect renal function. However, results from the Pediatric Health
      Information System database demonstrate no change in augmentation rates during
      this time and they demonstrate significant interinstitutional variability. To our
      knowledge this represents the largest series of augmentation cystoplasty in
      children with spina bifida to date.

PMID- 16945631
TI  - Ureterocystoplasty: videourodynamic assessment.
AB  - PURPOSE: We evaluated bladder function outcome in children who underwent
      ureterocystoplasty based on preoperative and postoperative videourodynamic
      studies. MATERIALS AND METHODS: Between 1977 and 2003, 8 patients with a median
      age of 6 years who had severe bladder dysfunction underwent ureterocystoplasty as
      a single surgical procedure. Augmentation was performed in 1 refluxing ureter in
      7 patients and with a nonrefluxing megaureter in 1. All patients were evaluated
      urodynamically before and after augmentation using videourodynamic studies.
      Preoperative bladder capacity was estimated subtracting the volume trapped inside
      the refluxing ureter from the total amount of contrast fluid infused into the
      bladder. Controls included 8 patients matched in age (median 7.8 years) and
      diagnosis who had undergone ileocystoplasty and were studied with the same
      urodynamic methodology. Median age in patients with ureterocystoplasty and
      controls at postoperative urodynamic testing was 7.3 and 11.2 years,
      respectively. RESULTS: Median cystometric bladder capacity for age before and
      after ureterocystoplasty was 75% (range 10% to 92%) and 94% (range 49% to 100%),
      respectively. In the ileocystoplasty group cystometric bladder capacity increased
      significantly after augmentation (median 44% vs 118, p <0.0005). Comparison of
      postoperative cystometric bladder capacity between the 2 treatment groups showed
      significantly higher bladder volumes in the ileocystoplasty group (median 217 vs
      290 ml, p <0.02). When we analyzed compliance before and after
      ureterocystoplasty, no statistically significant difference was found (4.09 vs
      10.5 ml/cm water). The same parameter in the ileocystoplasty group was
      statistically significant (1.6 vs 22.5 ml/cm water, p <0.016). CONCLUSIONS: Our
      retrospective study suggests that, although ureterocystoplasty is a useful method
      for improving bladder storage abnormalities in properly selected patients,
      enterocystoplasty is associated with a better storage function outcome.

PMID- 16945632
TI  - Distal shunt obstruction in children with myelomeningocele after bladder
      perforation.
AB  - PURPOSE: We studied short-term complications and particularly the signs of shunt
      dysfunction after augmented bladder perforation in patients with myelomeningocele
      and ventriculoperitoneal shunts. MATERIALS AND METHODS: In our series of bladder
      augmentations in 27 patients with myelomeningocele and a ventriculoperitoneal
      shunt in the last 10 years (1994 to 2004) we noted 4 who were 8 to 16 years old
      at our institute with bladder perforation 2 to 5 years after augmentation. Three
      patients received a colonic augmentation and 1 received an ileal augmentation.
      One patient underwent surgery for small bowel obstruction 2 years after the
      primary operation, when a hole in the augmented bladder was identified and
      oversewn. The other 3 bladder perforations occurred spontaneously or after
      failure to catheterize. An additional patient with spontaneous perforation
      underwent auto-augmentation elsewhere. RESULTS: After primary open abdominal
      surgery and enterocystoplasty there was no sign of shunt dysfunction in any
      patient. Bladder perforation and leakage of free urine into the abdominal cavity
      occurred in 4 of the 5 patients. In those patients severe symptoms of shunt
      dysfunction, including headache and high intracranial pressure, were noted 2 to 7
      days after perforation. In patient 1 there was only urine leakage into a small
      cavity close to the bladder and no acute signs of post-perforation shunt
      dysfunction. In all cases the shunt was externalized for 1 to 6 weeks without
      further complications. CONCLUSIONS: In patients with myelodysplasia who have
      bladder perforation and free urine in the abdominal cavity the peritoneum is
      chemically inflamed by urine. Resorption of cerebral liquor may be disturbed,
      leading to shunt dysfunction and high intracranial pressure. Therefore, it is
      important for the urologist to recognize and evaluate postoperative signs and
      symptoms of increased intracerebral pressure in patients with bladder
      perforation. If found, early computerized tomography of the brain is recommended.

PMID- 16945634
TI  - Outcome in patients who underwent tethered cord release for occult spinal
      dysraphism.
AB  - PURPOSE: Tethered cord syndrome encompasses a group of clinical symptoms caused
      by abnormal spinal cord fixation. We evaluated a select cohort of patients with
      primary tethered cord syndrome in regard to urodynamic and clinical outcome after
      cord release. MATERIALS AND METHODS: We retrospectively reviewed the records of
      patients with the diagnosis of tethered cord from May 2001 to October 2004.
      Patients were assessed preoperatively by standard urodynamic studies, which was
      repeated a mean of 6.4 months after tethered cord release. Clinical and
      urodynamic outcomes were analyzed. RESULTS: Ten male and 14 female patients 1
      month to 12 years old (median age 6 years) were evaluable. Preoperatively 14 of
      the 24 patients with a median age of 8.1 years were toilet trained and 7 (50%)
      had diurnal incontinence. Constipation was noted in 10 of 24 patients (42%) and
      urinary tract infections developed in 6 (25%). Postoperatively only 1 patient
      (7%) experienced diurnal incontinence (p = 0.04). Constipation was observed in 6
      patients (25%) and urinary tract infections developed in 1 (4.2%) (p = 0.29 and
      0.07, respectively). Ten of the 21 children (48%) with abnormal urodynamics had
      normalized studies postoperatively. Ten of the 17 patients with neurogenic
      detrusor overactivity achieved normalization and 7 remained unchanged. Two of 3
      patients with normal preoperative urodynamics had neurogenic detrusor
      overactivity and 1 had poor bladder compliance. Four patients with low bladder
      capacity and/or low compliance preoperatively did not improve. CONCLUSIONS: Our
      results suggest that tethered cord release is beneficial in terms of clinical and
      urodynamic outcomes. Patients with abnormal urodynamics had 48% improvement after
      tethered cord release. Neurogenic detrusor overactivity seems to respond better
      with 59% improvement in urodynamics. The level of the conus on magnetic resonance
      imaging did not seem to be predictive of urodynamic outcome. Patients with a
      normal bladder may show urodynamic deterioration postoperatively, which raises
      cause for concern.

PMID- 16945635
TI  - Abnormal urine flow in boys with distal hypospadias before and after correction.
AB  - PURPOSE: We established the urine flow rate and the effect of surgical correction
      on that rate in patients with hypospadias. MATERIALS AND METHODS: The urine flow
      rate, voided volume and residual urine were measured using an ultrasound flow
      probe and bladder scan in boys with distal hypospadias before operative
      correction in 42 with a mean age of 16 months, 3 and 9 months after operative
      correction in 28 and 11, respectively, and in a control group of 51 boys 0 to 3
      years old (mean age 11 months). Long-term flow data were obtained retrospectively
      from the records of 63 patients with hypospadias 1 to 10 years after operation.
      RESULTS: Of the controls 37% had mainly intermittent and sometimes fractionated
      flows, 4% had a plateau phase flow and 59% had mainly bell-shaped flow curves.
      The average maximum flow rate +/- SD was 6.8 +/- 4.1 ml per second and maximum
      flow rate/voided volume was 0.26 +/- 0.11 l per second. Of the boys with distal
      hypospadias 76% produced intermittent flows (fractionated in the majority) before
      correction. After correction this percent decreased to 50%. The average maximum
      flow rate was 7.5 +/- 2.5 ml per second before correction, and 6.6 +/- 2.8 and
      7.2 +/- 1.8 ml per second 3 and 9 months after operation, respectively. Average
      maximum flow rate/voided volume was 0.22 +/- 0.12 l per second before, and 0.16
      +/- 0.09 and 0.16 +/- 0.09 l per second 3 and 9 months after operation,
      respectively. In the long-term group maximum flow rate/voided volume was 0.13 +/-
      0.11 l per second. The number of patients voiding with a plateau phase increased
      from 6% before to 13% and 17% after correction, respectively. An obstructive
      pattern was also observed in 41% of the long-term followup group. CONCLUSIONS: An
      intermittent flow pattern is common in 0 to 3-year-old boys. It appears to be
      more common and more pronounced or fractionated in boys with distal hypospadias
      at the same ages. In relation to voided volume patients with hypospadias already
      produce an abnormally low urine flow rate before correction and even more so
      thereafter in the short and intermediate term. The corrective procedure increases
      the occurrence of flows with an obstructive pattern.

PMID- 16945637
TI  - Long-term followup of visual internal urethrotomy for management of short (less
      than 1 cm) penile urethral strictures following hypospadias repair.
AB  - PURPOSE: We reviewed the results of direct vision urethrotomy for short (less
      than 1 cm) penile urethral strictures following hypospadias surgery. MATERIALS
      AND METHODS: Patients with less than 1 cm anterior penile urethral strictures
      located proximal to the meatus underwent direct vision urethrotomy. Based on the
      type of initial urethroplasty patients were randomly divided into treatment with
      direct vision urethrotomy vs direct vision urethrotomy plus clean intermittent
      catheterization for 3 months. Success was defined as absent obstructive voiding
      symptoms and a normal urine flow 2 years following the last patient
      instrumentation. RESULTS: Of patients with urethral strictures following
      hypospadias repair 44% (32) had previously undergone tubularized graft
      urethroplasty and 56% (40) had previously undergone flap urethroplasty, including
      a tubularized island flap in 18, an onlay flap in 11 and urethral plate
      urethroplasty in 11. Direct vision urethrotomy alone was performed in 51% of
      patients (37), and direct vision urethrotomy and clean intermittent
      catheterization were performed in 49% (35). Success with the 2 methods was
      similar, that is 24% (9 of 37 patients) vs 22% (8 of 35). Following direct vision
      urethrotomy all patients with tubularized graft urethroplasty showed failure (0
      of 32). Success was noted in 11% of patients (2 of 18) with tubularized island
      flap urethroplasty compared to 72% (8 of 11) with onlay urethroplasty and 63% (7
      of 11) with urethral plate urethroplasty (each p <0.05). CONCLUSIONS: The
      addition of clean intermittent catheterization to direct vision urethrotomy does
      not improve the likelihood of success. Direct vision urethrotomy for short (less
      than 1 cm) urethral stricture usually fails following any type of tubularized
      graft or flap urethroplasty but it had moderate success following onlay flap and
      urethral plate urethroplasties.

PMID- 16945638
TI  - Feeling good in daily life: from the point of view of boys with posterior
      urethral valves.
AB  - PURPOSE: We determined what is important to feel good in daily life when living
      with a long-term illness that requires daily treatment routines. MATERIALS AND
      METHODS: Seven boys between 6 and 16 years old who were born with posterior
      urethral valves narrated their experiences with daily life. They were on clean
      intermittent catheterization, had impaired renal function and 2 had undergone
      transplantation. RESULTS: Being involved in decisions about themselves was
      important, as was having their own doctor and nurse. Friends were important.
      Clean intermittent catheterization was something that worried them in relation to
      friends and made them feel uncertain about how they would react to it. The boys
      accepted the catheterization procedure as something that had to be done but they
      needed strategies to be able to comply. A single event, such as no available
      toilet, was enough to interrupt treatment. CONCLUSIONS: In these boys prescribed
      treatment was a surprisingly small part of their lives. The clean intermittent
      catheterization routine was sometimes experienced as an obstacle in company with
      friends. The new challenge might be to achieve compliance with the treatment
      routine in daily life in a long-term perspective.

PMID- 16945639
TI  - Expression of cyclooxygenase-2 in Wilms tumor: immunohistochemical study using
      tissue microarray methodology.
AB  - PURPOSE: Cyclooxygenase-2, a key enzyme in prostaglandin biosynthesis, has been
      shown to be involved in the modulation of cell growth, inflammation and
      apoptosis. Its involvement in the development of several human neoplasms has also
      been documented as well as the significant antitumor effects of its inhibitors.
      To our knowledge cyclooxygenase-2 expression in Wilms tumor has not been studied.
      MATERIALS AND METHODS: A tissue microarray multitissue block was prepared from 14
      samples of Wilms tumor, each from a different patient, from xenografts derived
      thereof, and from normal human lung, liver, renal cortex and medulla tissues as
      controls. Each sample was represented in the block by 3 or 4 cores 0.6 mm in
      diameter. After serial slicing to 4 mum the histological slides were stained with
      hematoxylin and eosin, and immunostained with anti-cyclooxygenase-2 antibodies.
      Immunostaining was graded semiquantitatively according to the percent of stained
      cells with the cytoplasmic pattern of staining and according to staining
      intensity. RESULTS: All authentic human pathological samples except 1 anaplastic
      Wilms tumor as well as Wilms tumor xenografts expressed cyclooxygenase-2 in all
      Wilms tumor cellular components except the stroma. Expression was also observed
      in Wilms tumor lung metastasis and in tumors that overgrew chemotherapy. In
      comparison, cyclooxygenase-2 expression in normal kidneys was less prominent than
      in Wilms tumor samples and it was confined to the tubular epithelium in the
      cortex and medulla. CONCLUSIONS: Cyclooxygenase-2 expression is characteristic of
      all nonanaplastic Wilms tumors at all stages. It is similar to the previously
      observed pan-expression of ErbB2 receptors in these tumors. The potential
      therapeutic role of cyclooxygenase-2 inhibitors should be evaluated for Wilms
      tumor.

PMID- 16945640
TI  - Myogenin and desmin immunohistochemistry in the assessment of post-chemotherapy
      genitourinary embryonal rhabdomyosarcoma: prognostic and management implications.
AB  - PURPOSE: Posttreatment genitourinary embryonal rhabdomyosarcoma often shows well
      differentiated rhabdomyoblasts, which are detectable on routine histological
      staining. Definite areas of residual undifferentiated rhabdomyosarcoma indicate
      residual/recurrent disease. However, the recent use of immunohistochemical
      staining with desmin and myogenin in resected specimens and surveillance biopsies
      following adjuvant therapy may demonstrate scant positive staining cells that
      appear undifferentiated on light microscopy. To our knowledge the clinical
      significance of this finding is currently unknown. Therefore, we reviewed our
      retrospective experience with genitourinary embryonal rhabdomyosarcoma to examine
      the relationship between immunostain positive undifferentiated cells and
      subsequent clinical outcome. MATERIALS AND METHODS: A total of 14 children with a
      median age of 2.75 years (range 8 months to 7 years) with genitourinary embryonal
      rhabdomyosarcoma were identified in the histopathology database. All had biopsy
      confirmation of the diagnosis, followed by multi-agent chemotherapy. Two children
      in whom there was obvious residual active tumor at the resection margins were
      excluded from further analysis. Histopathological findings in all patients on the
      resection/posttreatment biopsy were reviewed. All specimens were immunostained
      with desmin and myogenin to detect residual undifferentiated rhabdomyoblasts. The
      relation between histopathological findings and outcome was determined. RESULTS:
      There were 14 cases of genitourinary embryonal rhabdomyosarcoma. In 2 cases (14%)
      residual embryonal tumor was pathologically confirmed following initial
      treatment. In 12 cases no obvious residual tumor was present following initial
      therapy. Rhabdomyosarcoma affected the bladder in 10 cases and the vagina in 2.
      There were no distant metastases in any child. Ten patients underwent local
      resection following chemotherapy and 2 underwent followup biopsies only without
      resection. A total of 11 cases showed well differentiated, posttreatment
      rhabdomyoblasts that was identifiable on routine hematoxylin and eosin staining
      with margins apparently free of tumor and 1 showed no morphological evidence of
      residual rhabdomyosarcoma. However, all cases demonstrated at least scant
      abnormal desmin and myogenin positive cells in the specimens. Four patients had
      no further treatment and none had clinical recurrence. All were well 10 years
      (range 8 to 13) after treatment. Eight patients received further treatment
      (chemotherapy and/or radiotherapy) based on clinical and pathological findings,
      followed by further resection in 3. One patient died of disease but 7 were well a
      median of 7.2 years (range 8 months to 13 years) after treatment. CONCLUSIONS:
      The significance of undifferentiated myogenin/desmin positive cells in
      genitourinary embryonal rhabdomyosarcoma in the absence of morphological
      residual/recurrent embryonal rhabdomyosarcoma remains unclear since such cells
      can be detected in all cases of posttreatment embryonal rhabdomyosarcoma. In some
      cases findings are associated with clinical disease recurrence, while others with
      identical histopathological findings following initial treatment have no clinical
      sequelae even in the absence of further treatment. In genitourinary embryonal
      rhabdomyosarcoma close and regular clinical surveillance is essential.
      Desmin/myogenin immunohistochemistry to detect scattered undifferentiated cells
      does not appear to provide useful prognostic information.

PMID- 16945641
TI  - Magnetic resonance urography for evaluating outcomes after pediatric pyeloplasty.
AB  - PURPOSE: We report the role of magnetic resonance urography in children with
      ureteropelvic junction obstruction. Differential renal function, the single
      kidney glomerular filtration rate index, renal transit time, renal length and
      renal pelvis anteroposterior diameter were compared before and after pyeloplasty.
      MATERIALS AND METHODS: Magnetic resonance urography was performed before and
      after pyeloplasty in 24 patients with a mean age of 1.9 years (range 3 months to
      10 years). Renal length, renal transit time and renal pelvis anteroposterior
      diameter were determined by the radiologist. The volume of functioning renal
      tissue and descending aorta were segmented and the ratio of the volumes of
      functioning kidney tissue was used to calculate differential renal function.
      Rutland-Patlak plots were used to calculate single kidney glomerular filtration
      rate index, that is the Patlak score. RESULTS: Mean renal pelvis renal pelvis
      anteroposterior diameter was 3.3 cm preoperatively and 2.5 cm postoperatively (p
      = 0.0003). There was no difference in average renal length (p = 0.22). Of the 24
      cases 22 (92%) showed stable or improved differential renal function. Improvement
      in renal transit time was seen in 20 of 23 cases (87%). Of 15 patients with
      complete Patlak scores 14 (93%) showed postoperative improvement. Mean
      preoperative and postoperative differential renal function, renal transit time
      and Patlak score were 36% and 41% (p = 0.003), 16.2 and 8.6 minutes (p = 0.0005),
      and 6.6 and 11.9 ml per minute (p = 0.01), respectively. CONCLUSIONS: Magnetic
      resonance urography provides superior anatomical and unprecedented functional
      information to fully define the preoperatively and postoperative status of
      corrected ureteropelvic junction obstruction. Magnetic resonance urography has
      the potential to become the imaging study of choice for evaluating pediatric
      hydronephrosis and obstructive uropathy.

PMID- 16945642
TI  - Long-term effects of dextranomer endoscopic injections for the treatment of
      urinary incontinence: an update of a prospective study of 61 patients.
AB  - PURPOSE: To treat sphincteric deficiency in children endoscopic bladder neck
      injections may avoid or salvage more complex procedures. A prospective study to
      assess the efficacy of bladder neck injections of dextranomer based implants
      (Deflux(R)) was done in a 7-year period in 61 patients. MATERIALS AND METHODS:
      From September 1997 to September 2004 we enrolled in the study 41 males and 20
      females 5 to 18 years old with severe sphincteric incompetence, including
      exstrophy-epispadias in 26, neuropathic bladder in 27, bilateral ectopic ureters
      in 5, and miscellaneous in 3. Preoperative evaluation consisted of medical
      history, urine culture, urinary tract ultrasound and videourodynamics. This
      evaluation was repeated 6 months and 1 year after treatment, and yearly
      thereafter. Of the patients 17 underwent 2 and 4 underwent 3 treatment sessions
      to achieve a definitive result. At each evaluation the case was considered cured
      a dryness interval of 4 hours between voids or CIC, significantly improved
      minimal incontinence requiring no more than 1 pad daily and no further treatment
      required, and treatment failure-no significant, long lasting improvement.
      Videourodynamics were mainly useful to study the evolution of bladder capacity,
      activity and compliance. Followup after the last injection was 6 to 84 months
      (mean 28). RESULTS: Mean injected volume per session was 3.9 cc (range 1.6 to
      12). Postoperative complications were temporary dysuria in 2 patients nonfebrile
      urinary tract infection in 10, orchid-epididymitis in 1 and urinary retention
      with pyelonephritis in 1. The incidence of dryness or improvement during followup
      was 79% (48 of 61 patients) at 1 month, 56% (31 of 55) at 6 months, 52% (24 of
      46) at 1 year, 51% (18 of 35) at 2 years, 52% (16 of 31) at 3 years, 48% (12 of
      25) at 4 years, 43% (9 of 21) at 5 years, 36% (4 of 11) at 6 years and 40% (2 of
      5) at 7 years. The success rate according to pathological condition was similar
      in cases of neuropathic bladder and the exstrophy-epispadias complex (48% and
      53%, respectively). The success rate in re-treated cases was 38%. After treatment
      a contracted bladder developed in 6 patients. Also, of the 35 patients with at
      least 2 years of followup an increase in capacity of at least 50% was observed in
      12 of 18 with an initially small bladder. No side effects related to the
      substance were observed. CONCLUSIONS: Endoscopic treatment for pediatric severe
      sphincteric deficiency with dextranomer implant, a nontoxic, nonimmunogenic,
      nonmigratory synthetic substance, was effective up to 2 years in half of the
      patients. Subsequently at up to 7 years of followup a slow decrease in efficacy
      was observed and treatment remained beneficial in 40% of the patients.

PMID- 16945643
TI  - Botulinum A toxin urethral sphincter injection in children with nonneurogenic
      neurogenic bladder.
AB  - PURPOSE: We evaluated botulinum-A toxin (Botox) injection into the urethral
      urinary sphincter in children with nonneurogenic neurogenic bladder to decrease
      urethral resistance and improve voiding. In these patients alpha-blocker
      medications had failed and injection was an alternative to unavailable
      biofeedback. MATERIALS AND METHODS: Prospective treatment was performed in 10
      children 6 to 17 years old (mean age 8) with nonneurogenic neurogenic bladder
      using botulinum-A toxin (Botox). Preoperatively all children were evaluated by
      ultrasound, voiding cystourethrography, excretory urography, magnetic resonance
      imaging and urodynamic studies, including pressure flow, electromyography and
      uroflowmetry. One patient had unilateral G3 reflux and 4 had bilateral G1 to G3
      hydronephrosis. Using a rigid pediatric endoscope and a 4Fr injection needle 50
      to 100 IU botulinum-A toxin were injected into the external sphincter at the 3, 6
      and 9 o'clock positions. Followup was 6 to 15 months. Repeat injections every
      month were given according to the response with a maximum of 3 injections.
      RESULTS: Immediately after botulinum-A toxin injection all except 1 patient were
      able to void without catheterization. No acute complications occurred. Four
      patients with bilateral hydronephrosis and the patient with the refluxing unit
      showed regression. Postoperatively post-void residual urine decreased by 89%,
      detrusor leak point pressure decreased significantly by a mean +/- SD of 66 +/-
      18 vs 37 +/- 4 cm H(2)O and uroflowmetry showed a marked increase in maximum
      urine flow of 2 +/- 2 vs 17.8 +/- 8 ml per second. Three injections were needed
      in 1 patient to attain the desired response. CONCLUSIONS: Urethral sphincter
      botulinum-A toxin injection could be considered a reliable treatment modality in
      children with nonneurogenic neurogenic bladder after the failure of conservative
      therapy.

PMID- 16945644
TI  - Proceedings of the Annual Meeting of the Section on Urology, American Academy of
      Pediatrics, Washington, DC, USA, October 9-11, 2005.

PMID- 16945646
TI  - Nocturnal enuresis in adolescents and adults is associated with childhood
      elimination symptoms.
AB  - PURPOSE: Since nocturnal enuresis in adults and adolescents is rarely
      monosymptomatic, we identified the prevalence of childhood bladder and bowel
      dysfunction, and compared findings to those in a normative cohort. MATERIALS AND
      METHODS: Childhood and current bladder and bowel dysfunction were investigated in
      56 consecutive adolescents and adults attending a public nocturnal enuresis
      service and in 293 normative adults using a self-administered questionnaire.
      Analysis involved descriptive statistics, the chi-square and Kruskal-Wallis
      tests, and regression analysis with p <0.05 considered significant. RESULTS:
      Adolescents and adults attending a public nocturnal enuresis service had
      significantly higher childhood scores than normative adults, and significantly
      more childhood urgency, frequency, urge incontinence, infrequent voiding and
      small volume, high urge voids. Infrequent bowel action and fecal soiling in
      childhood were also significantly more common in those with nocturnal enuresis
      than in controls. Adult symptoms of urge incontinence, general bowel symptoms and
      nocturnal enuresis were significantly more common in adults and adolescents with
      nocturnal enuresis. Significant associations were found between childhood
      symptoms and adult overactive bladder, and childhood emptying dysfunction and
      adult voiding dysfunction. Higher childhood scores in adults and adolescents with
      nocturnal enuresis correlated significantly with current adult symptoms of urge,
      urge leakage, stress incontinence, hesitancy, incomplete emptying and UTI within
      the last year. CONCLUSIONS: Significant childhood bladder and bowel symptoms
      along with more adult urge and bowel dysfunction were found in adults and
      adolescents with nocturnal enuresis. The association with adult urgency and
      urinary tract infection supports the likelihood of underlying bladder and or
      voiding dysfunction in unremitting nocturnal enuresis.

PMID- 16945647
TI  - Familial vesicoureteral reflux: influence of sex on prevalence and expression.
AB  - PURPOSE: Familial clustering of vesicoureteral reflux implies that genetic
      factors have an important role in the pathogenesis of vesicoureteral reflux. We
      investigated the impact of sex on familial vesicoureteral reflux. MATERIALS AND
      METHODS: Between 1998 and 2003 we identified 159 white families with at least 2
      children (range 2 to 5) with vesicoureteral reflux confirmed by a voiding
      cystourethrogram. Families were divided into 3 groups, including group 1 with
      only boys affected (29 or 18%), group 2 with only girls affected (57 or 36%) and
      group 3 with boys and girls affected (73 or 46%). Clinical characteristics,
      reflux grade and associated renal anomalies in these 3 groups were compared using
      the Mann-Whitney U and chi-square tests for statistical analysis. RESULTS:
      Sisters of index female patients were at significantly higher risk for
      vesicoureteral reflux than brothers (p <0.01). Boys in group 1 had a
      significantly higher grade of vesicoureteral reflux than boys in group 3, and
      girls in groups 3 and 2 (p = 0.018, <0.001 and <0.0001, respectively). Severe
      renal scarring was present in 7% of boys in group 1, 6.6% of boys in group 3,
      1.3% of girls in group 3 and 1.9% of girls in group 2. Duplex kidneys were
      present in 15.3% of boys in group 1 but only in 2.3% of boys in group 3 (p
      <0.01), 5.7% of girls in group 3 and 5.8% of girls in group 2. Age at diagnosis
      was not significantly different among boys in groups 1 and 3, and girls in group
      2 (median 0.9, 0.6 and 1.9 years, respectively). CONCLUSIONS: The risk and
      severity of vesicoureteral reflux in siblings depends on the sex of the affected
      child. Brothers of index male patients have higher grade of reflux and higher
      rate of associated duplex systems. This has implications for genetic counseling
      and for modeling the inheritance of vesicoureteral reflux.

PMID- 16945648
TI  - Magnetic resonance urographic parameters for predicting the need for pyeloplasty
      in infants with prenatally diagnosed severe hydronephrosis.
AB  - PURPOSE: Treatment in infants with prenatally diagnosed, severe hydronephrosis
      remains controversial. We measured anatomical parameters using magnetic resonance
      urography to create a pelvic index ratio, which we correlated with outcome to
      assess its value. MATERIALS AND METHODS: We reviewed 35 cases of prenatally
      diagnosed severe hydronephrosis, including grade III in 19 and grade IV in 16. By
      6 weeks after birth all patients had undergone repeat ultrasonography, diuretic
      renography and magnetic resonance urography. Magnetic resonance urography was
      used to measure the distance (D) from the bottom of the lowest renal calyx to the
      ureteropelvic junction and the total longitudinal length (L) of the caliceal
      system. The pelvic index ratio, defined as D/L, assesses the level at which the
      ureter inserts into the renal pelvis. RESULTS: All cases were initially managed
      conservatively. Pyeloplasty was required in 16 kidneys (mean patient age +/- SD
      7.5 +/- 3.9 months) because of deterioration in renal function. All patients were
      well at a mean followup of 3.8 years. The remaining 19 cases continued to be
      managed conservatively. By a mean of 5.4 years spontaneous resolution of
      prenatally diagnosed severe hydronephrosis had occurred in 7 of 19 cases, while
      12 were downgraded to grades I-II. The mean pelvic index ratio in surgical cases
      was 0.26 +/- 0.13 and in nonsurgical cases it was 0.12 +/- 0.11, indicating that
      ureters inserted significantly higher in surgical cases (p = 0.0012). Of 9
      kidneys with a pelvic index ratio of greater than 0.3 pyeloplasty was required in
      8, while 10 of 12 with a pelvic index ratio of less than 0.1 were managed
      conservatively. CONCLUSIONS: Pyeloplasty is likely to be required if the pelvic
      index ratio is greater than 0.3 and conservative management is likely to succeed
      if the ratio is less than 0.1. The pelvic index ratio can be calculated easily
      even in the neonatal period. It appears to be prognostic for pyeloplasty in cases
      of prenatally diagnosed, severe hydronephrosis.

PMID- 16945650
TI  - Magnetic resonance urography in the evaluation of prenatally diagnosed
      hydronephrosis and renal dysgenesis.
AB  - PURPOSE: We present our experience with dynamic contrast enhanced magnetic
      resonance urography for evaluation and treatment in infants born with prenatally
      recognized hydronephrosis. We determined the characteristics of renal dysgenesis
      in this population. MATERIALS AND METHODS: We reviewed magnetic resonance
      urography images done within the first 6 months of life in 67 infants born with
      prenatally recognized hydronephrosis. High resolution imaging was used to
      establish a morphological diagnosis. Functional evaluation was used to assess
      obstruction and individual renal function. Voiding cystourethrography was
      performed in 62 patients. RESULTS: Our study included 67 infants (87 renal
      units). There were 54 boys and 13 girls with a mean age of 2.8 months (range 0.9
      to 4.6). Of these 87 renal units 30 (35%) had ureteropelvic junction obstruction,
      18 (21%) had primary megaureters, 10 (11%) had nondilating vesicoureteral reflux,
      10 (11%) had fetal folds, 8 (9%) had posterior urethral valves, 6 (7%) had
      ectopic ureters, 4 (5%) had multicystic dysplastic kidneys and 1 (1%) had a
      normal study. Magnetic resonance urography revealed renal dysgenesis in 24 renal
      units (28%), consisting of loss of corticomedullary differentiation, renal cystic
      changes distinct from multicystic dysplastic kidneys, solid renal dysplasia,
      hypoplasia and dysmorphic calyces. CONCLUSIONS: Magnetic resonance urography is
      an excellent addition to our armamentarium for evaluating neonatal hydronephrosis
      and renal dysgenesis. Due to its comprehensiveness magnetic resonance urography
      has the potential to become the study of choice for evaluating infants with
      significant prenatally recognized hydronephrosis. However, further prospective,
      comparative studies in larger patient populations are needed to justify the cost
      and the need for sedation in infants.

PMID- 16945651
TI  - Urinary metabolic evaluations in normal and stone forming children.
AB  - PURPOSE: Urinary stone disease is relatively rare in children and urinary
      metabolic evaluations have been the standard in our practice. We have previously
      reported a high rate of urinary metabolic abnormalities in stone forming
      children. We compared urinary chemistry values in normal and stone forming
      children. MATERIAL AND METHODS: A prospective study was performed to assess
      urinary metabolic profiles in children with no history or a family history of
      urinary calculi. The 24-hour urine collections were performed and evaluated at an
      outside central laboratory. Urine chemistry studies were adjusted for creatinine.
      The data were compared to those on a historical cohort of calcium stone forming
      children. RESULTS: A total of 58 samples from normal children and 142 from stone
      forming children were evaluated. Mean age was 10 years in normal children and 12
      years in stone forming children. of the normal and stone forming children 45% and
      51%, respectively, were female. Supersaturation levels of calcium oxalate as well
      as calcium to creatinine levels were significantly higher in children with
      stones. No data confounding by age or sex was identified by stratification.
      CONCLUSIONS: There are significant differences in urinary metabolic evaluations
      between normal and stone forming children. This may allow more precise treatment
      to prevent recurrent stone episodes. We continue to perform metabolic evaluations
      in all children with documented urolithiasis.

PMID- 16945652
TI  - Renal transplantation in children 15 Kg or less: the British Columbia Children's
      Hospital experience.
AB  - PURPOSE: Small infants are the most challenging group of patients to undergo
      renal transplantation. PURPOSE: We reviewed the transplantation experience at our
      institution with children less than 15 kg at transplantation. MATERIALS AND
      METHODS: We retrospectively reviewed the records of 24 recipients in a 20-year
      period. Technical and allograft outcomes were compared to those in the North
      American Pediatric Renal Transplant Cooperative Study database. RESULTS: Since
      the inception of our program 24 recipients weighing 15 kg or less who were 6
      years or younger have undergone transplantation. Seven grafts (29%) were from
      living donors. At transplantation mean age was 3.1 years (range 1.8 to 5.7) and
      mean weight was 13.4 kg (range 9.0 to 15.7). Average cold and warm ischemic times
      were 14.1 hours (range 3.4 to 37.2) and 23.1 minutes (range 21 to 41),
      respectively. Early complications were ureteral stricture requiring
      pyeloureterostomy in 1 case, reversible acute tubular necrosis in 2 and early
      arterial thrombosis salvaged by immediate thrombectomy in 1. Delayed
      complications were arterial stenosis requiring angioplasty in 2 cases, and 3
      delayed deaths related to malignant hypertension in 2 and sepsis in 1. No grafts
      were lost due to thrombosis. Mean serum creatinine at years 1 to 3 and 5 were
      48.5, 67.5, 79.1 and 84.4 mumol/l, respectively. Graft survival was 92% (22
      patients after censoring 1 who died with a functioning graft) at 2 and 5 years.
      Overall results compare favorably to those in the North American Pediatric Renal
      Transplant Cooperative Study. CONCLUSIONS: With a multidisciplinary team effort
      successful results can be achieved in this challenging group of patients.

PMID- 16945653
TI  - What is the need for additional bladder surgery after bladder augmentation in
      childhood?
AB  - PURPOSE: Bladder augmentation has revolutionized the care of children with a
      neuropathic bladder but it remains a major surgical procedure. However, the need
      for subsequent bladder surgery has not been well defined in a large series with
      long-term followup. MATERIALS AND METHODS: We retrospectively reviewed the
      records of the first 500 bladder augmentations performed from 1978 to 2003 at our
      institution. Charts were reviewed for complications requiring additional surgery,
      including malignancy, bladder perforation, repeat augmentation, bowel obstruction
      and bladder calculi. Mean and median followup was 13.3 years. RESULTS:
      Complications occurred in 169 patients (34%) resulting in a total of 254
      surgeries. The cumulative risk of further surgery at the bladder level was 0.04
      operations per patient per year of augmentation. Three patients (0.6%) had
      transitional cell carcinoma, of whom all presented with metastatic disease and
      died. Bladder perforation occurred in 43 patients (8.6%) with a total of 53
      events. Of the patients 16 (3.2%) required laparotomy for bowel obstruction and
      47 (9.4%) required repeat augmentation. Bladder stones were treated in 75
      patients (15%), who required a total of 125 surgeries. CONCLUSIONS: Bladder
      augmentation provides immeasurable improvements in quality of life but it
      requires lifelong dedication from the patient, family and health care providers.
      While the requirements for additional surgery are not trivial, 66% of our
      patients have not required any further surgery in the augmented bladder.

PMID- 16945655
TI  - Review of 86 patients with myelodysplasia and neurogenic bladder who underwent
      sigmoidocolocystoplasty and were followed more than 10 years.
AB  - PURPOSE: We reviewed the long-term outcome of sigmoidocolocystoplasty. MATERIALS
      AND METHODS: The records of 86 patients who underwent sigmoidocolocystoplasty
      with a followup of more than 10 years were reviewed, focusing on histopathology,
      renal function, vesicoureteral reflux, bladder stones and urinary continence. We
      developed a urinary continence evaluation score, calculated as the postoperative
      minus the preoperative urinary continence score, including 0-incontinence, 1
      severe leakage, 2-moderate leakage, 3-mild leakage, 4-almost dry and 5-dry, for
      patient self-assessment of urinary continence. A score of 2 or more meant
      improvement and a score of less than 2 meant no improvement. RESULTS: Mean
      followup was 13.1 years (range 10 to 21). Histopathology showed inflammation in
      all cases, hyperplasia in 9 and metaplasia in 4. In 80 of 86 cases creatinine
      clearance was normal. Ureteral reimplantation had been performed before
      sigmoidocolocystoplasty in 9 cases (13 kidneys) for grades III to V
      vesicoureteral reflux, which recurred as grade I in 1 (1 kidney). Ureteral
      reimplantation was performed during sigmoidocolocystoplasty in 31 cases (58
      kidneys) and grades I to II vesicoureteral recurred in 5 (6 kidneys). Of the
      remaining 44 sigmoidocolocystoplasty cases there were 2 (2 kidneys) of grade I
      vesicoureteral reflux. On (99m)technetium-dimercapto-succinic acid scintigraphy
      there was increased renal scarring in 8 cases. Bladder stones were identified in
      18 of 86 cases during followup but they were absent at review. The urinary
      continence evaluation score showed improvement in 61 cases and no improvement in
      25. CONCLUSIONS: Our results suggest that sigmoidocolocystoplasty is safe and
      effective in the long term.

PMID- 16945656
TI  - Aesthetic aspects of bladder exstrophy: results of puboplasty.
AB  - PURPOSE: At times children born with bladder exstrophy-epispadias complex must
      undergo several operations and the resultant scar tissue on the abdomen can be
      quite disfiguring. Long-term followup in these patients reveals that many have a
      poor self-image, and the aesthetic aspects of the genitalia and lower abdomen
      acquire greater significance with age. We present our retrospective case series
      of the experience of 1 surgeon during 27 years. MATERIALS AND METHODS: Our
      database includes 116 patients born with exstrophy-epispadias complex. Primary
      reconstruction was performed in 62 infants and neonates, while 54 children and
      young adults underwent initial surgery elsewhere. Secondary puboplasty was
      performed in 88 of the 116 patients. Various techniques were used, ranging from
      simple excision and longitudinal closure in 12 cases, Z-plasty and pubic
      contouring in 23, the use of axial pattern inguinal skin flaps in 50 and tissue
      expanders in 3, when necessary. Long-term followup data were available on 76
      patients. The parent and, when appropriate, the patient determined satisfaction
      with the cosmetic appearance. RESULTS: Patient satisfaction with the cosmetic and
      functional outcomes of surgery was high. Of the 76 patients 73 (96%) were
      satisfied following puboplasty. Complications included wound infection and keloid
      formation in 4% and 10% of cases, respectively. CONCLUSIONS: Achievement of
      excellent aesthetic results is possible with secondary puboplasty. Simple closure
      is associated with a higher incidence of keloid formation compared to the Z
      plasty closure technique. Axial pattern skin flaps and Z-plasty techniques yield
      superior cosmetic results for contouring the mons pubis in patients with
      exstrophy-epispadias complex.

PMID- 16945657
TI  - Continent catheterizable channels and the timing of their complications.
AB  - PURPOSE: We reviewed our experience with continent catheterizable channels with
      interest in the timing of conduit related complications. MATERIALS AND METHODS: A
      retrospective review was performed of the outcome of continent catheterizable
      channels in all patients between 1998 and 2003 who had undergone construction of
      an antegrade continence enema and/or a Mitrofanoff procedure using appendix,
      small bowel or continent cutaneous vesicostomy. We performed a total of 117 such
      stomas in 37 male and 41 female patients 2.5 to 20 years old (mean age 8.9). For
      the antegrade continence enema we used appendix in 92% of cases, an ileal Yang
      Monti tube in 6% and a cecal tube in 2%. For the continent catheterizable channel
      we used appendix in 43% of cases, a Yang-Monti tube in 38% and continent
      cutaneous vesicostomy in 19%. RESULTS: Continence was achieved in 98% of
      patients. Followup was 6 to 71 months (mean 28.4). There were 27 channel related
      complications (23%). Stomal stenosis occurred in 7 antegrade continence enema
      procedures (14%) within 1 to 10 months (mean 6.2) and in 9 continent bladder
      channels (13%), including 5 continent cutaneous vesicostomies, within 1 to 24
      months (mean 9.4) after surgery. False passages occurred in 5 antegrade
      continence enema procedures (10%) within 1 to 13 months (mean 3.6) and in 4
      continent catheterizable channels (6%) within 1 to 13 months (mean 6.5) after
      surgery. Of patients with stomal stenosis 50% were treated with surgical
      revision, while the remainder was successfully treated with dilation. Most false
      passages were managed by catheter drainage alone. Reasons for revision were
      contained perforation, colovesical fistula and inability to catheterize. Patient
      noncompliance appeared to have a role in stomal stenosis. CONCLUSIONS: Continent
      catheterizable stomas help patients achieve bowel and bladder continence. Stomal
      incontinence after reconstruction is rare. In our experience most stoma related
      complications occurred in the first year after reconstruction. Experience with
      more patients and longer followup will help determine whether such problems
      continue to accumulate with time or whether continent stomas function well with
      time, particularly after the initial period of healing.

PMID- 16945659
TI  - 14 years of experience with the artificial urinary sphincter in children and
      adolescents without spina bifida.
AB  - PURPOSE: The efficacy of the artificial urinary sphincter to treat sphincteric
      incontinence in pediatric patients with spina bifida has been clearly reported.
      The possibility of maintaining spontaneous voiding has usually been the main
      reason for prosthetic device surgery. We reviewed our experience with the
      artificial urinary sphincter in patients without spina bifida who had had
      previous surgery of the bladder neck or proximal urethra. MATERIALS AND METHODS:
      From 1990 to 2004, 112 children and adolescents underwent implantation of an AMS
      800 artificial urinary sphincter. Of the patients 19 males and 4 females (20.5%)
      between ages 4 and 17 years (mean 8.1) had no spina bifida. Instead there were
      bladder exstrophy in 12 patients, anorectal malformation with a rectourethral or
      vesical fistula in 7 and epispadias in 4. A bladder neck cuff between 5.5 and 7.5
      cm, and a 61-70 balloon were used in all patients. RESULTS: Only 1 patient was
      lost to followup. In 22 patients (95.6%) mean followup was 80 months (range 4 to
      155). Three sphincters in patients with exstrophy were removed because of erosion
      and/or infection 5, 49 and 60 months after initial surgery, respectively. A total
      of 19 sphincters remained in place (86.3% survival rate) with 5 revisions (26.3%)
      because of the pump (2), the cuff (2) or balloon fluid leakage. In this group 13
      patients (68.4%) voided spontaneously and 6 (31.6%) performed clean intermittent
      catheterization, although 3 also voided spontaneously. Overall continence was
      good in 87% of patients because 2 were still incontinent at night. CONCLUSIONS:
      The artificial urinary sphincter is a good long-term solution to urinary
      incontinence secondary to sphincter incompetence despite multiple previous
      surgeries of the bladder neck or proximal urethra. Patients with bladder
      exstrophy and many previous bladder procedures are more exposed to complications
      such as erosion compared with patients with epispadias or anorectal malformation.
      The high percent of patients maintaining spontaneous voiding and the good rate of
      continence are the most important benefits of this type of surgical option for
      sphincter incompetence.

PMID- 16945660
TI  - Treatment of the occult tethered spinal cord for neuropathic bladder: results of
      sectioning the filum terminale.
AB  - PURPOSE: Occult tethered cord syndrome applies to patients with signs and
      symptoms consistent with a caudal spinal cord malformation despite normal
      neuroimaging. Although several reports of successful surgical treatment exist,
      controversy remains with respect to patient selection and efficacy. We present a
      large series with excellent clinical followup, neuroimaging and urodynamic
      characterization. MATERIALS AND METHODS: We present our experience with 36
      patients at a single institution with preoperative clinical findings,
      neuroimaging and urodynamics available. Postoperative outcomes were assessed
      clinically and with urodynamics. We determined predictive parameters to improve
      patient selection. RESULTS: Approximately 0.04% of pediatric urology clinic
      visits resulted in neurosurgical referral for the potential of an occult tethered
      cord. They occurred after failure of a mean of 2 years of aggressive medical
      management. Daytime urinary incontinence was present in 83% of patients and 47%
      had encopresis. Preoperative urodynamics were markedly abnormal in all patients
      with mean bladder capacity 55% of expected capacity. Clinical improvement in
      urinary symptoms was seen in 72% of patients with resolution of incontinence in
      42%. Bowel symptoms improved in 88% of cases, including resolution of encopresis
      in 53% within 3 months of surgery. Urodynamic improvements were demonstrated in
      57% of cases. We were unable to determine preoperative factors that were more
      likely associated with surgical success. CONCLUSIONS: In a highly select
      population with severe urinary and fecal dysfunction sectioning a normal
      appearing filum terminale can result in significant improvement. We were unable
      to identify factors that may increase the chance of surgical success.

PMID- 16945663
TI  - Urethral dilation as treatment for neurogenic bladder.
AB  - PURPOSE: We documented the change in bladder physiology and clinical outcomes
      after urethral dilation for managing neurogenic bladder. MATERIALS AND METHODS:
      Female patients with neurogenic bladder were identified who underwent urethral
      dilation due to failure to empty at low pressure or upper tract changes. Urethral
      dilation was performed using curved sounds to 36Fr (range 18Fr to 36Fr). Clinical
      charts were reviewed to document urodynamics, infection rates, symptomatology,
      vesicoureteral reflux and upper tract dilatation before and after dilation.
      RESULTS: A total of 19 children underwent urethral dilation a mean of 2 times.
      Mean age at first dilation was 19.3 months. Mean followup was 34.9 months. The
      indication for dilation was high detrusor leak point pressure in 16 children. The
      remaining children had recurrent infections (1), poor compliance (1) and bladder
      spasms (1). Clinical manifestations of increased detrusor leak point pressure in
      16 children were vesicoureteral reflux in 11, upper tract dilatation in 9 and
      recurrent infections in 3. Long-standing improvement occurred in 12 of 16
      patients with increased detrusor leak point pressure, in 0 of 1 with infection,
      in 0 of 1 with poor compliance and in 1 of 1 with bladder spasms. Overall
      improvement was noted in 13 of 19 cases (68%). Vesicoureteral reflux was
      identified in 14 of 19 patients. Improvement was seen in 6 of 14 cases, including
      complete resolution in 5 and improvement in 1. Hydronephrosis was seen in 11 of
      19 patients with improvement in 7, including resolution in 1 and improvement in
      6. Only 6 children required further surgical intervention, that is vesicostomy in
      2 and reimplantation in 4. CONCLUSIONS: Urethral dilation is effective for
      lowering detrusor leak point pressure in children with neurogenic bladder and for
      improving upper tract dilatation and vesicoureteral reflux. This procedure may
      prevent the need for more complicated surgical intervention. It should be
      investigated further in well designed, prospective studies.

PMID- 16945666
TI  - High yield of urodynamics performed for refractory nonneurogenic dysfunctional
      voiding in the pediatric population.
AB  - PURPOSE: In the pediatric population urodynamic evaluation for nonneurological
      causes has been previously reported as a low yield endeavor when considering
      patients with a primary diagnosis of dysfunctional voiding. We evaluated the rate
      of clinically significant urodynamic findings that would drive therapeutic
      intervention for a spectrum of urological disorders in pediatric patients without
      neurological deficit in whom initial conventional management had failed.
      MATERIALS AND METHODS: We retrospectively reviewed the charts of patients who had
      undergone urodynamics in the last 7 years. Patients with known neurological
      deficits were excluded. RESULTS: A total of 805 pediatric urodynamic evaluations
      were performed from December 1997 to July 2004 at our institution, including 89
      in patients with no known neurological diagnosis and charts available for review.
      Of the urodynamic studies 33 (37.1%) were reported as normal and 56 patients
      (62.9%) had clinically significant discoveries. Storage phase abnormalities were
      the predominant finding in 37 patients (66.1%), including uninhibited detrusor
      contractions in 31 (55.4%). Emptying phase abnormalities were less common (19
      patients or 33.9%). There was no difference in the percent of patients with
      positive urodynamics findings depending on sex. CONCLUSIONS: In our analysis
      evaluation of all recent urodynamics performed at a single institution revealed a
      high rate of pathological findings in patients with various nonneurological
      diagnoses.

PMID- 16945667
TI  - Bladder volume at onset of reflux on initial cystogram predicts spontaneous
      resolution.
AB  - PURPOSE: Reflux grade is the factor most commonly used to predict spontaneous
      reflux resolution. We evaluated other potential predictive factors aside from
      reflux grade relative to spontaneous resolution. MATERIALS AND METHODS: We
      reviewed the records of 20 males and 98 females who were diagnosed with primary
      vesicoureteral reflux between ages 0 and 7 years between 1990 and 2000. Age, sex,
      height, weight, reflux grade, bladder volume at onset of reflux and laterality
      were recorded for the first, second and most recent voiding cystourethrogram or
      nuclear cystogram before spontaneous resolution or operative intervention.
      RESULTS: Of 118 patients 75 (64%) had spontaneous resolution, 27 (23%) underwent
      corrective surgery and 16 (13%) are still being followed. Average age at
      diagnosis was 2.3 years (range 1 day to 7.7 years) and average followup was 4.3
      years (range 0.2 to 14). Average time to spontaneous resolution was 2.2 years
      (range 0.5 to 10.3) vs a time to operative treatment of 3.6 years (range 0.2 to
      11.2). There was a significantly higher spontaneous resolution rate for lower
      reflux grades (p = 0.0004). Reflux occurring at greater than 75% of predicted
      bladder capacity had a significantly higher resolution rate (p = 0.0005). The
      initial height and weight percentile was not significant for predicting
      spontaneous resolution. Breakthrough urinary tract infections were negative
      predictors of spontaneous resolution (p <0.0001). CONCLUSIONS: In addition to
      grade, bladder volume relative to predicted bladder capacity at the onset of
      reflux appears to provide additional prognostic information regarding the
      likelihood of spontaneous resolution of primary vesicoureteral reflux.

PMID- 16945668
TI  - Renal scarring in familial vesicoureteral reflux: is prevention possible?
AB  - PURPOSE: Detailed knowledge about risk factors for renal scarring in familial
      reflux is necessary to decide whether these factors could be influenced by early
      screening and treatment of siblings. We evaluated the prevalence of and risk
      factors influencing renal scarring in familial vesicoureteral reflux. MATERIALS
      AND METHODS: We reviewed the medical records and dimercapto-succinic acid scans
      of 306 children with familial vesicoureteral reflux. Scarring was classified as
      mild, moderate and severe. The impact of urinary tract infections, patient sex,
      reflux grade and age at diagnosis on renal scarring was evaluated. RESULTS: The
      prevalence of renal scarring was identical at 36% in 142 index patients and 74
      siblings presenting with urinary tract infection but it was only 10% in 87
      asymptomatic siblings (p <0.001) The difference between siblings with and without
      urinary tract infection was only statistically significant for mild scarring (23%
      vs 4.6%, p <0.001). It did not attain significance in those with moderate to
      severe scarring (13.5% vs 5.7%). Moderate to severe scarring was significantly
      more common in grade V than in grade IV refluxing units (43% vs 10%, p <0.0001)
      and in male than in female siblings (15.8% vs 3.4%, p = 0.012). Mild scarring was
      not significantly associated with reflux grade or patient sex. Children diagnosed
      before age 3 years showed significantly less scarring than patients diagnosed
      later (23% vs 41%, p <0.002). CONCLUSIONS: The development of mild renal scarring
      seems to mainly depend on urinary tract infections, while moderate and severe
      scarring are also associated with high grade reflux and male sex. Early detection
      and treatment may prevent further urinary tract infections as well as reflux
      related kidney damage.

PMID- 16945670
TI  - Endoscopic treatment for high grade vesicoureteral reflux in infants.
AB  - PURPOSE: Minimally invasive endoscopic treatment for vesicoureteral reflux has
      become an established alternative to long-term antibiotic prophylaxis and
      surgical intervention in children. We determined the long-term efficacy and
      safety of this treatment for high grade reflux in infants. MATERIALS AND METHODS:
      We retrospectively reviewed the medical records of 411 consecutive infants who
      underwent endoscopic treatment of grade III to V vesicoureteral reflux between
      June 1985 and October 2004. A total of 29 patients (7%) were excluded from study
      because they were lost to followup or the medical records were incomplete. Of the
      remaining 382 infants, including 203 males, 274 had bilateral and 108 had
      unilateral vesicoureteral reflux. This represented 642 high grade refluxing units
      with grade III to V disease in 232, 339 and 71, respectively. A dimercapto
      succinic acid scan performed in 312 infants revealed renal scarring in 88 (28%).
      The tissue augmenting substance used for endoscopic injection was
      polytetrafluoroethylene and dextranomer/hyaluronic acid copolymer in 432 and 210
      ureters, respectively. Endoscopic treatment was done at a median age of 7 months
      (range 2 months to 1 year). Median followup in these patients was 7 years (range
      6 months to 20 years). RESULTS: Complete resolution of vesicoureteral reflux
      after a single injection occurred in 443 ureters (69%), including 73% with
      dextranomer/hyaluronic acid copolymer and 65% with polytetrafluoroethylene. Of
      the 642 ureters 127 (20%) required more than 1 injection to correct
      vesicoureteral reflux. In 60 ureters vesicoureteral reflux was downgraded to
      grade I or II and no further treatment was given, while 12 ureters that failed to
      respond to endoscopic treatment required open surgical intervention. Only 1
      ureter required reimplantation to treat vesicoureteral obstruction. CONCLUSIONS:
      Endoscopic correction is a safe, effective, minimally invasive outpatient
      procedure for high grade vesicoureteral reflux in infants. Early correction of
      vesicoureteral reflux may provide protection from reflux associated renal damage
      and prolonged antibiotic use.

PMID- 16945671
TI  - What are the most powerful determinants of endoscopic vesicoureteral reflux
      correction? Multivariate analysis of a single institution experience during 6
      years.
AB  - PURPOSE: As the indications for endoscopic correction of vesicoureteral reflux
      continue to expand, the emergence of potential predictive variables has been
      noted. We used univariate and multivariate statistical analyses to find the most
      significant predictors of correction to improve patient selection. MATERIALS AND
      METHODS: A consecutive series of patients treated at a single institution was
      reviewed. Between August 1998 and August 2004, 232 children endoscopically
      injected with polydimethylsiloxane were identified, representing 351 refluxing
      units. A total of 23 variables were subjected to statistical analysis to detect
      predictors of reflux correction after injection. All identified patients with
      complete data and followup evaluations were included irrespective of anatomical
      variations, previous interventions or comorbidities. RESULTS: The overall success
      rate by patient and renal unit was 65% and 72%, respectively. In patients with a
      single system low grade (1-3) vesicoureteral reflux who did not previously
      undergo injection this success rate increased to 80%. Univariate analysis
      demonstrated that higher physician experience, low preoperative vesicoureteral
      reflux grade, absent renal scars and no previous injections were statistically
      significant predictors of vesicoureteral reflux correction (p <0.05). A history
      of febrile urinary tract infections and a duplex system did not attain
      significance (p = 0.069 and 0.076, respectively). On multivariate statistical
      evaluation only physician experience, preoperative vesicoureteral reflux grade
      and the number of previous injections remained significant. CONCLUSIONS:
      Multivariate analysis of our data showed the most important determinants of
      vesicoureteral reflux correction after endoscopic injection. Prospective
      validation will allow us to generate nomograms to better select and counsel
      patients who would benefit from vesicoureteral reflux treatment.

PMID- 16945672
TI  - Subureteral dextranomer/hyaluronic acid injection as first line treatment in the
      management of high grade vesicoureteral reflux.
AB  - PURPOSE: Endoscopic correction of vesicoureteral reflux has become an established
      alternative to long-term antibiotic prophylaxis and ureteral reimplantation. A
      number of tissue augmenting substances have been used for the endoscopic
      correction of vesicoureteral reflux. We prospectively evaluated the effectiveness
      of dextranomer/hyaluronic acid copolymer (Deflux) as first line treatment for
      high grade vesicoureteral reflux. MATERIALS AND METHODS: Between 2001 and 2004,
      692 children with a median age of 2.1 years (3 months to 13.7 years) with high
      grade vesicoureteral reflux underwent endoscopic subureteral injection of Deflux
      soon after the diagnosis of vesicoureteral reflux was made on the initial voiding
      cystourethrogram. Vesicoureteral reflux was unilateral in 283 patients and
      bilateral in 409. Of the 1,101 ureters vesicoureteral reflux was grade II to V in
      35 (3.2%), 580 (52.7%), 457 (41.5%) and 29 (2.6%), respectively. The procedure
      was performed on an outpatient basis. Followup ultrasound and voiding
      cystourethrogram were performed 3 months after the procedure, and renal and
      bladder ultrasound was done annually. RESULTS: Reflux resolved after first,
      second and third endoscopic Deflux injections in 952 (86.5%), 130 (11.8%) and 19
      ureters (1.7%), respectively. Followup ultrasound revealed no evidence of delayed
      vesicoureteral junction obstruction. Of the patients 18 (2.6%) had urinary tract
      infection during followup after successful vesicoureteral reflux correction.
      CONCLUSIONS: Endoscopic subureteral injection of Deflux is excellent first line
      treatment in children with high grade vesicoureteral reflux. This 15-minute
      outpatient procedure is safe and simple to perform, and it can be easily repeated
      in failed cases.

PMID- 16945674
TI  - Endoscopic injection of dextranomer/hyaluronic acid copolymer to correct
      vesicoureteral reflux following failed ureteroneocystostomy.
AB  - PURPOSE: The efficacy of endoscopic injection of dextranomer/hyaluronic acid to
      correct primary vesicoureteral reflux is well documented. We present experience
      at 2 institutions with endoscopic treatment for vesicoureteral reflux after
      failed ureteroneocystostomy. MATERIALS AND METHODS: A retrospective review was
      performed of the records of all patients who underwent endoscopic
      dextranomer/hyaluronic acid injection to correct vesicoureteral reflux following
      ureteral reimplantation between April 2002 and July 2005. De novo ipsilateral
      vesicoureteral reflux was noted after repair of primary nonrefluxing megaureters
      or renal transplantation and persistent vesicoureteral reflux was noted following
      attempted vesicoureteral reflux repair. Injection was performed using the
      standard technique if the ureteral orifice was easily accessible, and
      percutaneously if access was difficult. RESULTS: Nine male and 9 female patients
      were identified. Median age was 1.9 years at reimplantation and 6.5 years at
      injection, and median followup was 19 months. Ten patients underwent extravesical
      detrusorrhaphy and 8 underwent cross-trigonal reimplantation. Six patients
      underwent reimplantation for primary megaureter repair and all had resolution of
      vesicoureteral reflux with injection. Of the 20 renal units 16 (80%) and 15 of 18
      patients (83%) had complete resolution of vesicoureteral reflux after 1
      injection. One patient had improvement in vesicoureteral reflux and 2 had no
      improvement. There were no complications resulting from injections. CONCLUSIONS:
      Endoscopic treatment of vesicoureteral reflux with dextranomer/hyaluronic acid
      following extravesical or cross-trigonal reimplantation is safe and efficacious,
      at least at short-term followup. Endoscopic injection should be considered first
      line treatment for this situation.

PMID- 16945675
TI  - The evolution of vesicoureteral reflux management in the era of
      dextranomer/hyaluronic acid copolymer: a pediatric health information system
      database study.
AB  - PURPOSE: Since Food and Drug Administration approval of Deflux, injection therapy
      for vesicoureteral reflux has increased. Little data exist on the effect that
      injection therapy has had on the incidence of ureteral reimplantation and total
      vesicoureteral reflux procedures. We used the Pediatric Health Information System
      database to define practice trends for vesicoureteral reflux therapy. MATERIALS
      AND METHODS: From 2002 to 2004 we extracted data on 0 to 19-year-old patients
      with International Classification of Diseases-9 diagnosis codes for
      vesicoureteral reflux, and procedure codes for ureteral reimplantation and
      subureteral injection therapy. Of 37 hospitals enrolled in Pediatric Health
      Information System 18 submitted ambulatory surgery and inpatient data. Data on
      the total number of patients who underwent reimplantation and injection were
      analyzed using linear regression analysis for trend. RESULTS: We identified a
      total of 4,570 procedures performed in 1,948 patients treated with injection
      therapy and in 2,483 treated with reimplantation. The mean number of injections
      per institution yearly increased from 17 to 66 from 2002 to 2004 or 288%, while
      the mean number of reimplantations yearly was not statistically different from
      2002 to 2004 (p = 0.02 and 0.09, respectively). In addition, the annual mean
      number of vesicoureteral reflux procedures per institution increased from 75 to
      116 or 55% (p <0.05), primarily due to the increased number of injections.
      CONCLUSIONS: With the introduction of a new, minimally invasive procedure for
      reflux therapy the number of procedures for reflux has increased, while open
      surgery rates have remained stable. This may be explained by public and clinician
      acceptance of a newer injection material that is safe and increasingly
      successful. To our knowledge this represents the largest series of patients
      treated for vesicoureteral reflux in the United States.

PMID- 16945676
TI  - Has the growth and development of subspecialization in pediatric urology affected
      scholarly activity?
AB  - PURPOSE: How has academic productivity changed in a decade in the American
      Academy of Pediatrics Section on Urology? Do academic pursuits slow as section
      members become older? What is the average number of publications yearly by
      section members? What percent of research is funded in pediatric urology? Has
      change occurred with multiple authorships? MATERIALS AND METHODS: American
      Academy of Pediatrics Urology Section active memberships for 1993 and 2003 were
      obtained. A PubMed study was performed by reviewing all manuscripts published by
      American Academy of Pediatrics Section on Urology active members for 1991 to 1993
      and 2001 to 2003. The data recorded were author, year, PubMed identification
      number, the number of authors, financial support and journal. Parametric and
      nonparametric statistics were used for analysis. RESULTS: In the 1991 to 1993 era
      there were 245 active members, of whom 145 published a total of 972 manuscripts.
      There were 604 clinical authorships, 161 basic science articles, 42 reviews and
      186 case reports, of which 154 manuscripts received funding. In the 2001 to 2003
      era there were 252 members, of whom 177 published a total of 1,152 manuscripts.
      There were 773 clinical authorships, 140 basic science articles, 107 reviews and
      124 case reports, of which 151 manuscripts receiving funding. For members in the
      2 periods the mean number of articles decreased by 1.0 from 1 decade to the next
      (p = 0.002). CONCLUSIONS: Scholarly pursuit of pediatric urology as a
      subspecialty has remained remarkably steady, averaging about 2 authorships per
      author yearly in the recent decade. The percent of authorships with funding in
      pediatric urology has decreased. The number of funded authorships has remained
      steady. A higher percent of American Academy of Pediatrics members have published
      manuscripts in the last decade. More manuscripts were published during the last
      decade study period than during the prior decade. The mix of manuscript types has
      changed with more reviews, and fewer case reports and basic science authorships
      in the most recent decade. New members are more likely to publish with a low
      unpublished percent.

PMID- 16945677
TI  - A meta-analysis of surgical practice patterns in the endoscopic management of
      ureteroceles.
AB  - PURPOSE: We examined the contribution of patient features on reoperation after
      transurethral incision or puncture in children with ureteroceles. MATERIALS AND
      METHODS: A systematic review was accomplished using Medline and article
      bibliographies to obtain articles related to endoscopic management of
      ureteroceles in English, Spanish, Italian, French and Japanese. Exposures of
      interest were ureterocele position and anatomy, and preoperative reflux. The
      outcome was secondary operation. Meta-analysis was done using Mantel-Haenszel
      calculations. RESULTS: Meta-analysis of 10 studies demonstrated that ectopic
      ureteroceles are associated with significantly greater reoperation rates than
      intravesical ureteroceles in patients undergoing ureterocele incision. This
      remains true with longer followup and systematic ureterocele incision/puncture,
      in neonates and in patients with single and duplex collecting systems. In
      addition, a meta-analysis of 3 studies showed that patients with duplex system
      ureteroceles are more likely to require subsequent operation. A third meta
      analysis of 7 studies showed that preoperative reflux increases the risk of
      reoperation after ureterocele incision. More than 1 risk factor did not appear to
      increase the risk of secondary operation. CONCLUSIONS: To our knowledge this is
      the first systematic review of endoscopic ureterocele management. It suggests
      that ectopic ureterocele location, duplex renal systems and preoperative reflux
      are proxies for trigonal anatomical distortion, rather than independent risk
      factors for a secondary operation after incision. Findings reinforce the
      importance of considering these variables when making management decision in
      children with ureteroceles.

PMID- 16945679
TI  - Prospective, longitudinal evaluation of health related quality of life in the
      pediatric spina bifida population undergoing reconstructive urological surgery.
AB  - PURPOSE: Spina bifida, the most frequent permanently debilitating birth defect,
      results in major urological problems of voluntary bladder control and bowel
      function, which may impair quality of life. We prospectively assessed quality of
      life in patients with spina bifida using child and parent reports simultaneously.
      This study had 3 goals, that is to 1) document baseline health related quality of
      life in patients with spina bifida preoperatively, 2) study health related
      quality of life, reporting differences between parents and children, and 3) study
      changes in health related quality of life prospectively at preoperative and
      postoperative intervals. MATERIALS AND METHODS: Patients with spina bifida who
      were 2 to 18 years old and required reconstructive urological surgery in 2004
      were included in the study. Demographic survey and the validated PedsQL 4.0
      health related quality of life questionnaire were used preoperatively and
      postoperatively. A clinical outcomes data set was completed after the clinician
      saw the patient. PedsQL 4.0 subscales were scored using the algorithms provided.
      RESULTS: The response rate was 100%. Mean participant age was 10.3 years.
      Preoperatively child physical and psychosocial health and school functioning were
      significantly higher than parent reports (p <0.001). Overall health related
      quality of life in patients with spina bifida was lower than in healthy children
      (62.4 vs 85, p <0.001). Six weeks postoperatively significant differences in
      health related quality of life reporting between parents and children had
      lowered. Six months postoperatively child emotional and social functioning scores
      were higher than parent scores (p <0.001). No correlation was found between
      health related quality of life, and clinical and demographic factors due to
      insufficient sample size. CONCLUSIONS: Children with spina bifida recorded higher
      health related quality of life scores than parents/guardians. This health related
      quality of life study addresses concerns that impact daily quality of life in
      patients with spina bifida. Future health related quality of life studies in
      patients with spina bifida should use child self-reports.

PMID- 16945680
TI  - Ontogeny of androgen receptor and disruption of its mRNA expression by exogenous
      estrogens during morphogenesis of the genital tubercle.
AB  - PURPOSE: The ontogeny of androgen receptor expression in male and female mouse
      genital tubercles, and the effects of in utero ethinyl estradiol exposure on
      androgen receptor mRNA expression in the hypospadias model were studied.
      MATERIALS AND METHODS: Androgen receptor mRNA expression was measured in mouse
      genital tubercles from fetuses and pups collected on gestational days 12, 14, 16
      and 18, and from newborns using immunohistochemistry and real-time quantitative
      polymerase chain reaction. Pregnant dams were exposed to ethinyl estradiol or
      corn oil as controls from gestational days 12 to 17. Genital tubercles of
      gestational day 19 fetuses were then examined by further quantitative polymerase
      chain reaction analysis after identification of the seam area using a dissecting
      microscope to diagnose hypospadias in males. RESULTS: Androgen receptor protein
      was detected in genital tubercles by gestational day 14. Androgen receptor mRNA
      expression increased gradually in each sex during normal development. However,
      female genital tubercles expressed a higher level of androgen receptor mRNA
      throughout development compared to male genital tubercles (p <0.0001). In utero
      ethinyl estradiol exposure led to a 5.4 and 4.5-fold increase in androgen
      receptor mRNA in the genital tubercles of female and male embryos (p = 0.004 and
      0.001, respectively). Hypospadiac male genital tubercles showed increased
      androgen receptor mRNA expression compared to control males (p = 0.006). Levels
      in hypospadiac males did not differ from those in control females but they were
      less than those in ethinyl estradiol treated females (p >0.05 and 0.01,
      respectively). CONCLUSIONS: Androgen receptor protein is expressed abundantly in
      male and female genital tubercles. Androgen receptor mRNA levels are higher in
      female than in male genital tubercles through development and they increase in
      response to in utero ethinyl estradiol exposure with ethinyl estradiol treated
      females having the highest levels of expression, followed by ethinyl estradiol
      treated hypospadiac males. We infer that higher estrogen in genital tubercles
      results in a physiological response of increased androgen receptor mRNA
      expression. We found no direct association between changes in androgen receptor
      mRNA expression and the presence or absence of hypospadias in males, suggesting
      that alterations in the expression of proteins other than or in addition to
      androgen receptor result in anomalous urethral development. This finding supports
      the idea that the etiology of hypospadias is multifactorial in origin.

PMID- 16945681
TI  - Long-term cosmetic and sexual outcome of hypospadias surgery: norm related study
      in adolescence.
AB  - PURPOSE: Even if performed early in life, hypospadias surgery may have a
      significant impact on self-esteem and sexual behavior in adolescence. We
      evaluated the long-term cosmetic and sexual outcomes of hypospadias surgery
      performed in childhood. MATERIALS AND METHODS: A detailed questionnaire was
      mailed to 33 patients with hypospadias who were 18 to 26 years old and had
      undergone the first operation at age 6 years or younger. It was also mailed to 50
      age matched controls. RESULTS: A total of 22 patients (66.7%) and 38 controls
      (76.0%) returned the questionnaire. Mean age in the hypospadias and control
      groups was 20.6 and 21.0 years, respectively. Eight of the 22 patients had mild
      hypospadias and 11 had severe hypospadias. Severity was unknown in 3 patients.
      Age at the first and final operations was 31 to 75 (mean 46) and 35 to 81 months
      (mean 53). The number of operation was 1 in 10 patients, 2 in 10 and 3 in 2. The
      rate of dissatisfaction with penile appearance was slightly higher in the
      hypospadias group than in the control group (40.9% vs 34.2%). The single reason
      for dissatisfaction in the hypospadias group was inadequate penile size, whereas
      in the control group penile size, phimosis and curvature were the major reasons
      for dissatisfaction (69.2%, 46.2% and 23.1%, respectively). Experience with
      masturbation (100% and 97.4%) and sexual intercourse (52.4% and 55.3%), and mean
      age at first masturbation (13.4 and 13.0 years) and first sexual intercourse
      (16.6 and 17.3 years) were similar in the hypospadias and control groups,
      respectively. CONCLUSIONS: Although patients with hypospadias had a slightly
      higher rate of dissatisfaction with penile size, their sexual behavior was not
      different from that in control subjects.

PMID- 16945683
TI  - On effects of trawling, benthos and sampling design.
AB  - The evidence for the wider effects of fishing on the marine ecosystem demands
      that we incorporate these considerations into our management of human activities.
      The consequences of the direct physical disturbance of the seabed caused by towed
      bottom-fishing gear have been studied extensively with over 100 manipulations
      reported in the peer-reviewed literature. The outcome of these studies varies
      according to the gear used and the habitat in which it was deployed. This
      variability in the response of different benthic systems concurs with established
      theoretical models of the response of community metrics to disturbance. Despite
      this powerful evidence, a recent FAO report wrongly concludes that the
      variability in the reported responses to fishing disturbance mean that no firm
      conclusion as to the effects of fishing disturbance can be made. This thesis is
      further supported (incorrectly) by the supposition that current benthic sampling
      methodologies are inadequate to demonstrate the effects of fishing disturbance on
      benthic systems. The present article addresses these two erroneous conclusions
      which may confuse non-experts and in particular policy-makers.

PMID- 16945684
TI  - Risk factors for nosocomial urinary tract-related bacteremia: a case-control
      study.
AB  - BACKGROUND: Risk factors for bacteremia in patients with hospital-acquired
      bacteriuria are largely unknown. Given the morbidity and costs associated with
      nosocomial bacteremia, determining risk factors could enhance the safety of
      hospitalized patients. METHODS: We conducted a case-control study within the
      Veterans Affairs Puget Sound Health Care System. A patient hospitalized between
      1984 and 1999 from whom a urine culture and a blood culture grew the same
      organism > or =48 hours after admission was considered a case. Control patients
      were those with significant bacteriuria detected > or =48 hours after admission
      who did not have a positive blood culture. We used logistic regression to
      determine independent risk factors for bacteremia. RESULTS: There were 95 cases
      and 142 controls. Independent, statistically significant predictors of bacteremia
      included immunosuppressant therapy within 14 days of bacteriuria (odds ratio
      [OR], 8.13); history of malignancy (OR, 1.94); male sex (OR, 1.88); cigarette use
      in the past 5 years (OR, 1.26); number of hospital days before bacteriuria (OR,
      1.03); and antibiotic use within 3 days of bacteriuria (OR, 0.76). Corticosteroid
      use within 7 days of bacteriuria predicted bacteremia in patients <70 years old
      (OR, 14.24). Similarly, patients <70 years old were more likely to develop
      bacteremia if they had diabetes mellitus (OR, 6.19). CONCLUSION: Delineating risk
      factors for nosocomial urinary tract-related bacteremia can help target
      appropriate preventive practices at the highest risk patients.

PMID- 16945685
TI  - Impact of contact isolation on health care workers at a tertiary care center.

PMID- 16945686
TI  - Nurses and emergency disasters: what is known.
AB  - Following the events of September 11, 2001, the threat of bioterrorism events has
      become a realistic concern for health care workers in the United States.
      Bioterrorism events caused by infectious agents will be challenging because
      nurses will need to recognize unfamiliar infections and work long hours with
      limited resources in stressful conditions. During a bioterrorism event caused by
      biologic agents, nurses will be expected to provide care to infected patients and
      may fear that they, or their families, could also become infected. A review of
      literature suggests that nurses' response to working during a bioterrorism event
      is not well described. The limited number of studies regarding nurses' concerns,
      fears, and anxieties is focused on nurses' experiences in natural disaster or war
      situations. Additional studies are needed to validate the appropriateness of
      applying findings from disaster response studies to bioterrorism events. During
      bioterrorism events, nurses will be expected to provide physical care and
      emotional and psychologic support for victims and victims' families. Realistic
      bioterrorism plans should incorporate strategies to support nurses and address
      their physical, psychologic, and emotional issues. Strategies to optimize safe
      working conditions and minimize psychologic trauma such as technical training
      regarding bioterrorism agents and debriefing opportunities should be included.

PMID- 16945687
TI  - Comparison of bacterial counts in glove juice of surgeons wearing smooth band
      rings versus those without rings.
AB  - BACKGROUND: Removal of rings is recommended before surgeons aseptically prepare
      for surgical procedures. OBJECTIVES: This study was undertaken to determine
      whether there is a difference between bacterial counts under surgical gloves of
      ring wearers compared with nonring wearers after proper aseptic hand preparation
      and 3 hours of wear. METHODS: Twenty volunteer veterinary medical students were
      divided into 2 groups: One group wore a smooth ring band (without projections or
      mounted stones) on their ring finger, and the other group did not wear a ring. A
      modified glove juice method was used to obtain bacterial counts (colony-forming
      units/mL) inside surgically gloved hands prior to a proper aseptic hand
      preparation and 3 hours after hand preparation and wear. Each of the pre- and
      postsurgical glove juice samples were inoculated onto Letheen agar plates, which
      were incubated aerobically under atmospheric conditions for 48 hours at 35
      degrees C. Gloves were tested for perforations using a water pressure test.
      RESULTS: No differences, or significant change, in bacterial counts were found
      before or after surgery between all ring hands and nonring hands or between ring
      and nonring hands for ringed participants. No differences in bacterial counts
      were found within perforated versus nonperforated gloves. CONCLUSION: There is no
      compelling evidence to suggest that surgeons wearing rings possess higher
      bacterial counts under their gloves during surgery.

PMID- 16945688
TI  - Infection control in German nursing homes.
AB  - Infection control in German nursing homes has become an issue during the past 10
      years. The changing demographics and the introduction of the diagnosis-related
      group reimbursement system, as well as the increasing number of residents who are
      colonized with methicillin-resistant Staphylococcus aureus, may worsen already
      existing infection control problems. The publication of national infection
      control guidelines for nursing homes that should be implemented and supervised by
      infection control nurses may increase the standard. However, the lack of
      responsibility of the caring physicians for the whole population of a nursing
      home may hinder the process. This article discusses the state of infection
      control in German nursing homes.

PMID- 16945690
TI  - Errors committed by nursing technicians and assistants in administering
      antibiotics.
AB  - BACKGROUND: Success in any antibiotic treatment depends on many factors,
      including the associated preparation procedures and the nursing care management.
      OBJECTIVE: The aim of this research was to analyze errors in nursing procedures
      in the use of cefepime. METHODS: A survey was performed in the adult patients'
      wing of a university hospital in Brazil, and a direct observation technique was
      used to process variation errors. Errors were classified by type. RESULTS: Thirty
      three nursing assistants were observed and interviewed as they prepared and
      administered cefepime on 99 occasions. From our sample, 20 (20%) applications
      were performed correctly but 126 errors were observed in 79 cases (80%). The
      majority (62%) of errors detected were time (scheduled and rate) related. Trained
      personnel executed the procedure for diluting the solution better than nontrained
      personnel, but no other statistically significant effect related to the knowledge
      level of the personnel was detected. This study concluded that errors occurred
      during care of patients because lack of specific procedures, such as adequate
      planned rate of infusion and schedule time. They were classified in an American
      Society of Health-System Pharmacists scheme. It is recommended that corrective
      practice and safety measures be introduced.

PMID- 16945689
TI  - The establishment of a statewide surveillance program for hospital-acquired
      infections in large Victorian public hospitals: a report from the VICNISS
      Coordinating Centre.
AB  - BACKGROUND: A 1998 survey of acute Victorian public hospitals (VPH) revealed that
      surveillance of hospital-acquired infections (HAI) was underdeveloped,
      definitions and methodology varied considerably, and results disseminated
      inconsistently. The survey identified the need for an effective surveillance
      system for HAI. OBJECTIVE: To develop and support a standardized surveillance
      program for HAIs in large acute VPH and to provide risk-adjusted, procedure
      specific, HAI rates. METHODS: In 2002, the independent Victorian Nosocomial
      Infection Surveillance System (VICNISS) Coordinating Centre (VCC) was established
      to develop and support the standardized surveillance program. A multidisciplinary
      team was recruited. A communication strategy, surveillance manual, user groups,
      and Web site were developed. Formal education sessions were provided to
      participating infection control nurse consultants (ICCs). Surveillance activities
      were based on the US Centers for Diseases Control and Prevention's National
      Nosocomial Infection Surveillance System (NNIS) surgical site infection and
      intensive care unit (ICU) components. NNIS methods were modified to suit local
      needs. Data collection was paper based or through existing hospital software. An
      advisory committee of key stakeholders met every second month. RESULTS: The
      surveillance program was rolled out over 12 months to all 28 large adult VPH.
      Data on over 20,000 surgical procedures performed at participating sites between
      November 11, 2002, and December 31, 2004, were submitted. Thirteen hospitals
      contributed to the ICU surveillance activities. Following aggregation and
      analysis by the VCC, hospital- and state-level results were posted on the Web
      page for hospitals to review. CONCLUSION: A standardized approach for
      surveillance of HAI was established in a short time frame in over 28 VPH. VICNISS
      is a tool that will continue to provide participating hospitals with a basis for
      continuous quality improvement.

PMID- 16945692
TI  - Risk factors for vancomycin-resistant Enterococcus faecalis bacteremia in
      hospitalized patients: an analysis of two case-control studies.
AB  - BACKGROUND: Vancomycin-resistant enterococci (VRE) is an important pathogen in
      the hospital environment, and a progressive increase in its incidence is a cause
      of nosocomial infections. Bacteremia is one of the major infections caused by
      this pathogen. Risk factors for VRE bacteremia were assessed at a university
      affiliated hospital. METHODS: Two case-control studies with different control
      groups were used. In study 1, patients with VRE bacteremia were compared with
      control patients matched by sex, admission unit, age (+/-10 years), and time of
      admission (+/-1 year). In study 2, the case group (VRE patients) was compared
      with vancomycin-susceptible enterococci (VSE) patients. RESULTS: A total of 34
      patients with VRE bacteremia and 102 control patients were included in study 1,
      and 34 patients with VRE bacteremia and 55 patients with VSE bacteremia were
      included in study 2. In study 1, vancomycin use (OR, 10.19; CI 95%, 3.63-28.57)
      was associated with VRE bacteremia. In study 2, vancomycin use (OR, 17.58; CI
      95%, 5.24-58.96) was also associated with VRE bacteremia. CONCLUSION: Because
      vancomycin use was the only variable associated with VRE bacteremia in the two
      studies, we confirmed that vancomycin exposure is the major risk factor for VRE
      bacteremia.

PMID- 16945691
TI  - Pseudooutbreak of Pantoea species bacteremia associated with contaminated cotton
      pledgets.
AB  - A total of 22 isolates of Pantoea strains, unusual causative agents of clinical
      infection, was isolated from blood cultures from 9 patients and 1 ear swab from 1
      of the patients within a period of 1 month in a tertiary-care hospital.
      Pseudooutbreak was suspected because specimens were collected from a limited
      number of places and the patients did not show consistent signs or symptoms of
      bacterial sepsis. Enterobacterial repetitive intergenic consensus (ERIC)
      polymerase chain reaction (PCR) and partial 16S ribosomal DNA sequencing were
      performed to determine the clonal relationship among the isolates. Screening
      environmental cultures revealed that cotton pledgets were contaminated with
      Pantoea species. Molecular typing suggested that 2 different clones of Pantoea
      strains were responsible for the pseudooutbreak. Cotton materials may be a
      possible source of Pantoea pseudooutbreak. Molecular typing is useful for
      investigating epidemics and identifying unusual clinical isolates.

PMID- 16945693
TI  - Social marketing: a behavior change technology for infection control.
AB  - Changing health care worker behaviors is a core function of infection control
      programs. The social change technologies of education and institutional policy
      are limited in their capacity to achieve desired behaviors on a sustained basis
      because they do not address the importance of opportunity and ability in practice
      enhancement. Social marketing addresses the health care worker's lack of
      opportunity and ability by offering a bundle of benefits at low cost with high
      accessibility and by doing this better than the behavioral status quo. This
      article introduces some social marketing concepts and explicates them in the
      context of hand hygiene promotion.

PMID- 16945694
TI  - Multihospital surveillance of nosocomial methicillin-resistant Staphylococcus
      aureus, vancomycin-resistant enterococcus, and Clostridium difficile: analysis of
      a 4-year data-sharing project, 1999-2002.
AB  - BACKGROUND: This study sought to establish a benchmark of resistant organism
      rates among a cohort of regional hospitals. METHODS: The Centers for Disease
      Control and Prevention (CDC) definitions were used to standardize the methodology
      for obtaining rates per 1000 patient days of nosocomial infection and
      colonization with methicillin-resistant Staphylococcus aureus (MRSA) and
      vancomycin-resistant enterococcus (VRE), and nosocomial infection with
      Clostridium difficile (CDIF). Only newly acquired nosocomial cases were counted.
      Data were reported as individual hospital control charts and as cohorted
      aggregate data. VHA East Coast Infection Control Professionals from 32 hospitals
      in New Jersey and Pennsylvania were involved. RESULTS: Benchmarks were
      established with pooled mean rates for each cohort. During the observational
      period, a statistically significant downward trend was observed for VRE and MRSA
      (P = .02 and .0007, respectively), and an upward trend was observed for CDIF (P =
      .0256). CONCLUSION: Benchmarks were established to compare nosocomial MRSA, VRE,
      and CDIF rates. Although significant changes in rates were observed, no attempt
      was made to establish a causal relationship between infection control practices
      and observed rates. However, a secondary gain was achieved through sharing best
      practices.

PMID- 16945695
TI  - Compliance with hepatitis B virus vaccine: a matter of force?
AB  - BACKGROUND: Vaccination for hepatitis B virus has been mandatory in Italy since
      1991 for newborns but not for workers exposed to biologic fluids. METHODS: The
      immunologic status against hepatitis B virus was investigated in 827 paramedical
      students of Padua University Medical School. The students were subdivided
      according to sex and 2 age groups: 24 years of age or less and older than 24
      years because subjects aged 24 years or less were probably included in the
      Italian vaccination mandatory period. RESULTS: Subjects born during the mandatory
      period showed a large compliance to vaccination (94.9%) and without statistically
      significant difference between males and females compared with the oldest
      students (67.6%). CONCLUSION: The prevention at work is a matter of public
      health, not an individual sensitivity. For this reason, the devices to prevent
      accidents and diseases should be mandatory for all exposed subjects.

PMID- 16945696
TI  - Re: Reduction in nosocomial infection with improved hand hygiene in intensive
      care units of a tertiary care hospital in Argentina, by Rosenthal et al.

PMID- 16945697
TI  - Assessment of infection surveillance and control programs in nursing homes.

PMID- 16945698
TI  - HA cleavage site mutation in bird flu virus in Thailand: relation to pathogenic
      degree and further surveillance.

PMID- 16945702
TI  - Structure and format of peer-reviewed scientific manuscripts.

PMID- 16945703
TI  - William Darrach, MD: his life and his contribution to hand surgery.
AB  - William Darrach popularized subperiosteal resection of the distal ulna for distal
      radioulnar joint dysfunction, a procedure also known as the Darrach procedure. He
      was also a major contributor to academic surgery and medical education,
      publishing at least 70 articles, most on the treatment of fractures. He was
      influential in organized medicine and served as Dean of the Columbia College of
      Physicians and Surgeons, Governor and Regent of the American College of Surgeons,
      President of the American Surgical Association, and President of the Association
      of the American Medical Colleges. His contributions to education, hand surgery,
      and fracture treatment methodology make him an important figure in medicine.

PMID- 16945704
TI  - Low-profile dorsal plating for dorsally angulated distal radius fractures: an
      outcomes study.
AB  - PURPOSE: Controversy exists surrounding the effectiveness and complications
      associated with dorsal plating for distal radius fractures. This study evaluated
      the functional outcome of dorsal plating for dorsally angulated distal radius
      fractures at a single institution. METHODS: Thirty patients formed the study
      cohort. All plates were low profile and stainless steel. Radiographic parameters,
      range of motion, and strength compared with the uninjured side were recorded. The
      functional outcome was evaluated by the Disabilities of the Arm, Shoulder, and
      Hand questionnaire and the Gartland and Werley scoring system. RESULTS: The
      median patient age at surgery was 59 years. The median follow-up period was 18
      months. According to the AO classification system, there were 4 type A fractures,
      5 type B fractures, and 21 type C fractures. The median preoperative dorsal
      angulation was 30 degrees, and the median postoperative angulation was -4 degrees
      volar. Sixteen patients with fractures had an intra-articular step-off or gap,
      which were all corrected to neutral by the procedure. Seven patients with the
      fractures showed positive ulnar variance, all corrected to neutral at time of
      follow-up evaluation. Compared with the contralateral side, the mean extension
      and flexion were 88% and 81%, respectively; pronation and supination were 89% and
      87%, respectively; and grip strength and thumb pinch were 78% and 94%,
      respectively. The mean postoperative Disabilities of the Arm, Shoulder, and Hand
      questionnaire score was 15 points, and 28 patients had Gartland and Werley scores
      of good or excellent. No patients needed to have their plates removed, and no
      extensor tendon rupture was reported. One patient lost reduction, 1 patient
      needed a tenolysis of the extensor pollicis longus tendon, and 2 patients
      required the removal of a single metaphyseal screw. CONCLUSIONS: Results from
      this study show that patients can expect to have 80% of their range of motion and
      strength after dorsal plating for distal radius fractures. Moreover, 93% of the
      patients will have good to excellent functional outcomes. Complications from
      dorsal plating may be caused by the specific plate used, rather than by the
      technique itself, supporting a dorsal approach for dorsally angulated distal
      radius fractures.

PMID- 16945705
TI  - Incidence and demographics of hand fractures in British Columbia, Canada: a
      population-based study.
AB  - PURPOSE: To identify population-based hand fracture annual incidence rates,
      demographics, and seasonal and geographic variations from all patients seeking
      treatment for a hand fracture in British Columbia, Canada from May 1, 1996 to
      April 20, 2001. METHODS: All Medical Service Plan and Hospital Separation records
      that included International Classification of Diseases-9 codes for metacarpal
      (815), phalangeal (816), and multiple (817) fractures were extracted from the
      British Columbia Linked Health Dataset, along with the individual registry
      demographic records linked to each hand fracture. RESULTS: A total of 72,481 hand
      fractures were identified. Fifty percent were phalangeal fractures, 42% were
      metacarpal fractures, and 8% were multiple fractures. The total population annual
      incidence rate for a hand fracture was 36 per 10,000. Age-adjusted annual
      incidence rates ranged from 29 per 10,000 for people older than 20 years to 61
      per 10,000 for people age 20 or younger. The most common age for a hand fracture
      was 14 years for males and 13 years for females. Males had a 2.08 greater
      relative risk for hand fracture and they maintained most of this increase in risk
      between the ages of 15 and 40. For females there was an increased relative risk
      for a hand fracture after the age of 65. Spring had the highest rates for hand
      fractures. People in the Northern half of the province had a 1.6 greater relative
      risk for sustaining a hand fracture, compared with people in the more urbanized,
      less-industrialized, and more-affluent Southwestern region. CONCLUSIONS: Our
      study provides a robust projection of annual incidence rates for hand fractures
      because we were able to review all occurrences of a hand fracture within a
      population base of approximately 4 million people over a 5-year period. Our study
      also allowed for the examination of how age, gender, season, and geographic
      location influenced hand fracture incidence rates within a large, diverse
      population.

PMID- 16945706
TI  - Vascularized bone blocks from the toe phalanx to solve complex intercalated
      defects in the fingers.
AB  - PURPOSE: Vascularized bone transplants resist infection and allow rapid healing
      but keeping small bony segments vascularized, as needed for a finger defect, is a
      challenge. The purpose of this article is to present a cohort of patients with
      traumatic intercalated compound bony defects in the fingers that were
      reconstructed by a vascularized toe phalanx (or part of a phalanx) in a single
      stage. METHODS: Eight patients were treated with an intercalary vascularized bone
      graft that included a part of the proximal phalanx (3 patients), most of the
      middle phalanx (4 patients), or a portion of each phalanx (1 patient) of a second
      toe (totaling 9 bone blocks). There was an associated soft-tissue defect in each
      patient, an infection in 6 patients, and cartilage loss in 4 patients. The toes
      were pedicled on the proper digital artery (6 patients) or a segment of the first
      dorsal metatarsal artery (2 patients). A mean length of 12 mm of vascularized
      bone was transferred. The associated skin island varied from a minimum of 2 x 1
      cm to a maximum of 5 x 3 cm. Bleeding from all of the bone surfaces was evidenced
      once the clamps were released. The homolateral digital nerve and the
      contralateral neurovascular pedicle of the toe were kept in place. The toe defect
      was treated by soft-tissue arthroplasty or arthrodesis. No toe was amputated.
      RESULTS: Radiologic bony union was evident at 4 to 6 weeks, except in 1 patient
      with an acute infection whose distal union failed to unite at 6 weeks because the
      infection recurred. Finger length loss averaged 3 mm. All patients returned to
      their preoperative occupation. CONCLUSIONS: In this group of patients the toe
      phalanx reliably maintained its vascularization, allowing us to solve compound
      osteocutaneous defects in the fingers in a single stage. Donor site morbidity was
      minimal.

PMID- 16945707
TI  - Locked intramedullary nailing of metacarpal fractures secondary to gunshot
      wounds.
AB  - PURPOSE: To investigate the results of fixation of 10 metacarpal shaft fractures
      secondary to low-velocity gunshot wounds with locked intramedullary nails.
      METHODS: We reviewed the results of 10 patients with locked intramedullary
      nailing of the metacarpal for low-velocity gunshot wounds. Autogenous bone
      grafting was used in 9 of the 10 fractures. The follow-up period averaged 26
      months. The parameters evaluated included angulation, rotational alignment,
      shortening of the digit, postoperative metacarpophalangeal (MCP) range of motion,
      and time to union. RESULTS: Nine of 10 fractures showed corticocancellous bone
      autograft incorporation in the midshaft of the metacarpal on radiographs 3 months
      after surgery; the single fracture without bone grafting did not unite and
      required an additional procedure with bone grafting to achieve union. The MCP
      flexion averaged 81 degrees. All MCP joints attained full extension except for 2
      that had a 10 degrees extension lag. One metacarpal required an extensor tendon
      tenolysis and an MCP capsulotomy. No malrotation of the digits was noted and none
      of the patients developed an infection. The average shortening was 1.2 mm and 1
      metacarpal had an angulation of 6 degrees. CONCLUSIONS: Locked intramedullary
      nailing of the metacarpal with autogenous iliac crest bone graft is an effective
      technique for treating low-velocity gunshot metacarpal fractures associated with
      bone loss and comminution. The locked implant maintains satisfactory alignment,
      length, and rotation of the metacarpal until graft incorporation and bone healing
      occurs.

PMID- 16945708
TI  - Ultrasound in the diagnosis of ulnar neuropathy at the cubital tunnel.
AB  - PURPOSE: Ulnar neuropathy at the cubital tunnel (UCT) is diagnosed on the basis
      of history, physical examination, and nerve conduction studies (NCSs); however,
      the wide spectrum of findings often makes the diagnosis difficult. The purpose of
      this study was to document the ultrasonographic differences in ulnar nerve size
      between patients with UCT and control subjects, and to correlate those
      differences with clinical examination findings and NCS abnormalities, thereby
      testing the validity of ultrasound (US) as an additional adjunct diagnostic
      modality for UCT. METHODS: Fifteen elbows in 14 patients with symptoms, clinical
      examination, and NCS findings consistent with UCT had US of the ulnar nerve.
      Patients were excluded if they had a history of polyneuropathy, acute trauma
      involving the upper extremity, previous trauma in the region of the elbow
      (including previous surgery), or brachial plexus injury. The control group
      consisted of 60 elbows from 30 normal volunteers that also had US. Maximal cross
      sectional areas (CSAs) were measured and compared for the 2 groups and a
      correlation analysis was performed between nerve size and NCS findings. RESULTS:
      The average CSA of the ulnar nerve was 0.065 cm(2) in the control group, whereas
      in the UCT group it was 0.19 cm(2), indicating a significant statistical
      difference in ulnar nerve size between the 2 groups. The Pearson correlation
      coefficient between motor nerve conduction velocity of the ulnar nerve and the
      CSA was 0.80. CONCLUSIONS: High-resolution US is a noninvasive, safe, and
      reliable modality for imaging the ulnar nerve at the elbow and it may provide a
      valuable adjunct to NCS in the diagnosis of UCT.

PMID- 16945709
TI  - Innervated reverse dorsal digital island flap for fingertip reconstruction.
AB  - PURPOSE: Various methods of fingertip reconstruction with a sensory flap have
      been reported. Digital island flaps or cross-finger flaps have to be used for
      large defects; however, the digital artery is sacrificed when creating
      conventional homodigital island flaps and 2 surgeries are required for the cross
      finger flap. We describe our experience with an innervated reverse dorsal digital
      island flap that does not require sacrifice of the digital artery. METHODS: We
      used innervated reverse dorsal digital flaps for fingertip reconstruction in 8
      patients. The flap was supplied by the vascular network between the dorsal
      digital artery (the terminal branch of the dorsal metacarpal artery) and the
      dorsal branch of the digital artery. Venous drainage was through the cutaneous
      veins and the venous network associated with the dorsal arterial network. The
      flap was designed on either the dorsal proximal or the dorsal middle phalangeal
      region. The flap was harvested with the dorsal branch of the digital nerve (for
      the dorsal middle phalanx), the dorsal digital nerve (for the dorsal proximal
      phalanx), or the superficial branch of the radial nerve (for the thumb), which
      was anastomosed to the distal end of the digital nerve. After flap transfer the
      donor site was covered with a full-thickness skin graft. RESULTS: Of the 8 flaps,
      6 survived completely, 1 had partial epithelial skin necrosis, and 1 showed
      central compression skin necrosis. Three flaps showed congestive changes from the
      first to the fifth day after surgery, which resolved by massage. All patients
      achieved satisfactory recovery of sensation; the static 2-point discrimination
      ranged from 3 mm to 5 mm and the Semmes-Weinstein test results ranged from 0.036
      g to 0.745 g. CONCLUSIONS: The innervated reverse dorsal digital island flap
      provides another option for homodigital tip coverage. The advantages are that the
      digital artery is not sacrificed and only 1 surgery is needed. A disadvantage is
      the potential for venous congestion for the first 4 or 5 days after surgery.

PMID- 16945710
TI  - Hourglass-like constriction of the axillary nerve: report of two patients.
AB  - Among the various etiologies of compressive lesions, the development of an
      hourglass-like constriction of the nerve that is unrelated to any recognizably
      compressive structure is a very rare phenomenon. This problem has been reported
      previously for the radial nerve and its branch posterior interosseous nerve and
      for the anterior interosseous nerve, a branch of median nerve. Here we report 2
      cases of hourglass-like constriction of the axillary nerve that were observed
      during surgery; the constrictive segment was unrelated to any compressive
      structure.

PMID- 16945712
TI  - Intrinsic muscle contribution to the metacarpophalangeal joint flexion moment of
      the middle, ring, and small fingers.
AB  - PURPOSE: To analyze the relative contribution of the intrinsic muscles to the
      flexion moment potential of the metacarpophalangeal (MCP) joints of the middle,
      ring, and small fingers and to calculate the moment potential loss occurring with
      deep motor branch, low, or high ulnar nerve palsy or low median nerve palsy.
      METHODS: Eleven fresh cadaver hands were used. A small wire sutured to each
      tendon was connected to an excursion transducer containing a constant-tension
      spring. The tendon excursion and the MCP joint rotation were measured
      simultaneously during 10 to 16 cycles of passive flexion/extension cyclic motion.
      The moment arm was calculated from the tendon excursion-joint rotation curve as
      the derivative of the curve. The flexion moment potential was calculated by
      multiplying the moment arm with the known tension fractions of the muscles.
      RESULTS: When the MCP joint was at 0 degrees of flexion the relative moment
      potential contributions of the intrinsic muscles to MCP joint flexion were 8%,
      13%, and 28% in the middle, ring, and small fingers, respectively. Moment
      potential losses were 7%, 13%, and 6% in the middle, ring, and small fingers,
      respectively, in deep motor branch ulnar nerve palsy. In low ulnar nerve palsy
      the losses were 7%, 13%, and 28%, respectively. In high ulnar nerve palsy they
      were 7%, 64%, and 82%, respectively. Low median nerve palsy, however, resulted in
      a moment potential loss at the middle finger MCP joint of less than 2%.
      CONCLUSIONS: The relative contribution of the intrinsic muscles to the total
      flexion moment at the MCP joint was different for each finger. The small finger
      had a large intrinsic contribution, primarily because of the larger moment arms
      of the hypothenar muscles.

PMID- 16945711
TI  - Passive muscle-tendon amplitude may not reflect skeletal muscle functional
      excursion.
AB  - PURPOSE: To quantify the gain in muscle mobility with progressive release of
      surrounding connective-tissue structures and to compare this property with the
      known architecture of each muscle. METHODS: Each of 5 different muscle tendon
      units (extensor carpi radialis brevis, extensor carpi radialis longus, flexor
      carpi ulnaris, flexor digitorum superficialis, pronator teres) was released from
      its insertion and secured into the jaws of a clamp attached to a servomotor that
      could be operated under length or force control to simulate the load placed on
      the tendon by a surgical assistant. A constant load of 5 N was applied to the
      tendon while the muscle-tendon unit was released surgically from the surrounding
      tissue in 1-cm increments. Mobility was plotted against release distance and
      analyzed by linear regression to yield mobility gain, the slope of the regression
      equation. One-way analysis of variance was used to compare mobility gain among
      muscles. RESULTS: In contrast to previous results from the brachioradialis muscle
      in which the mobility gain was large and highly nonlinear, mobility gain was
      small, consistent, and linear for all muscles studied. The smallest mobility gain
      was for the flexor digitorum superficialis and was highly linear. The largest
      gain was for the pronator teres and again was highly linear. In general, the
      mobility gain for the extensor carpi radialis brevis was similar to that of the
      extensor carpi radial longus. The flexor carpi ulnaris muscle was difficult to
      mobilize, and its gain was modest. There was no significant correlation between
      mobility gain of the forearm muscles during progressive release and the length of
      their fibers. CONCLUSIONS: The small mobility and complete lack of correlation
      with fiber length provide strong evidence that mobility gain does not accurately
      reflect muscle excursion as it is typically described. This calls into question
      the general practice of tensioning muscles by first passively extending the
      muscle and then choosing the attachment length as a particular portion of that
      passive relationship.

PMID- 16945713
TI  - Analysis of relative motion splint in the treatment of zone VI extensor tendon
      injuries.
AB  - PURPOSE: Early protected motion after extensor tendon repair is desirable. The
      low-profile relative motion splint, described previously by Merritt et al, holds
      the affected digit in 15 degrees of extension relative to the uninjured digits to
      allow less-cumbersome early protected motion versus dynamic splinting. Although
      early clinical results have been favorable, formal biomechanic testing of this
      approach is lacking. We used an in vitro model to assess the effect of the low
      profile relative motion splint on the biomechanics of zone VI extensor tendons by
      measuring tendon elongation with and without the splint. Tendon elongation also
      was measured after transection and repair of extensor tendons in zone VI with and
      without splint protection. METHODS: Ten fresh-frozen cadeveric upper extremities
      were prepared and mounted on a testing apparatus with the wrist in 25 degrees of
      extension. Alternating applications of extension and flexion loads to the tendons
      induced a full range of motion for 25 cycles. Differential variable reluctance
      transducers were applied to zone VI of the index, middle, and ring extensor
      tendons. Measurements of intact tendon microelongation (or strain) were obtained
      with and without the relative motion splint. The middle finger extensor tendon
      then was transected (in zone VI) and was repaired immediately. Measurements were
      repeated with and without splint protection. Elongation ratios were calculated
      and analyzed statistically. RESULTS: For the intact tendon of the middle finger
      splinting reduced the elongation by 1% in extension, by 2% in flexion, and by 3%
      in neutral position. After the transection and repair of this same tendon, the
      splint reduced the elongation by 5% in extension, by 7% in flexion, and by 6% in
      neutral position. Cycling without splint protection caused permanent stretching
      at the repair site. Reapplication of the splint decreased elongation at the
      repair site by 2% in extension, by 3% in flexion, and by 3% in neutral position.
      CONCLUSIONS: The relative motion splint reduces the effective strain on intact
      and repaired zone VI middle finger extensor tendons and supports its clinical
      use.

PMID- 16945714
TI  - A histologic analysis of the effects of stainless steel and titanium implants
      adjacent to tendons: an experimental rabbit study.
AB  - PURPOSE: The current trend is to treat distal radius fractures with open
      reduction and internal fixation with either titanium or stainless steel plates.
      Both provide stable fixation; however, there is minimal evidence concerning the
      soft-tissue response to these materials. Our objective was to evaluate the
      response of adjacent extensor tendons to titanium and stainless steel in a rabbit
      in vivo model and to evaluate the influence of time. METHODS: Forty rabbits were
      divided into 5 groups of 8 rabbits each. Groups I and II had unilateral osteotomy
      of the distal radius followed by dorsal fixation with titanium and stainless
      steel plates, respectively. Groups III and IV had fixation with titanium and
      stainless steel, respectively, but without osteotomy. Group V had surgical
      dissection without osteotomy or plates. Two animals per group were killed at 1,
      4, 12, and 24 weeks. The specimens (distal radius, plate, overlying soft tissue,
      and extensor tendon) were harvested en bloc for histologic analysis. For
      interface preservation between implant and tissues the specimens were embedded in
      methylmethacrylate, sectioned, and stained with hematoxylin-eosin. RESULTS:
      Histologic analysis showed a fibrous tissue layer formed over both implants
      between the plate and the overlying extensor tendons in the groups treated with
      plating independently of the material and the presence or absence of osteotomy.
      This fibrous layer contained the majority of debris. Metallic particles were not
      observed in the tendon or muscle substance of any animals; however, they were
      visualized in the tenosynovium. Hematoxylin-eosin-stained sections of groups I
      through IV showed proliferative fibroblasts and metallic particles; however, this
      layer was not observed in group V. Statistical analysis did not show differences
      between the groups regarding the number of cells or metallic particles.
      CONCLUSIONS: Our results indicate that both implants generated adjacent reactive
      inflammatory tissue and particulate debris. There was no difference in cell or
      particle number produced by both materials. There is a statistically significant
      increase in inflammatory cells with increasing time of implantation.

PMID- 16945715
TI  - Pulsed magnetic field therapy increases tensile strength in a rat Achilles'
      tendon repair model.
AB  - PURPOSE: To examine the effect of pulsing electromagnetic fields on the
      biomechanic strength of rat Achilles' tendons at 3 weeks after transection and
      repair. METHODS: This noninvasive modality was tested in a prospective,
      randomized, double-blinded, placebo-controlled study to evaluate the effect of a
      specific noninvasive radiofrequency pulsed electromagnetic field signal on tendon
      tensile strength at 21 days post transection in a rat model. RESULTS: In the
      animals receiving PMF exposure, an increase in tensile strength of up to 69% was
      noted at the repair site of the rat Achilles' tendon at 3 weeks after transection
      and repair compared with nonstimulated control animals. CONCLUSIONS: The
      application of electromagnetic fields, configured to enhance Ca(2+) binding in
      the growth factor cascades involved in tissue healing, achieved a marked increase
      of tensile strength at the repair site in this animal model. If similar effects
      occur in humans, rehabilitation could begin earlier and the risk of developing
      adhesions or rupturing the tendon in the early postoperative period could be
      reduced.

PMID- 16945716
TI  - The wettability of intrasynovial and extrasynovial tendons.
AB  - PURPOSE: The surface properties of biologic materials are important to their
      observed physiochemical responses, mechanical interactions, and compatibility
      with other materials. The purpose of this study was to characterize further the
      surface properties of canine tendons, specifically how they interface with fluids
      -that is, their wettability. METHODS: Drop-shape analysis was used to study
      contact angles on intrasynovial and extrasynovial tendon surfaces. This standard
      goniometric method was used to estimate tendon-wettability properties. RESULTS:
      This study showed that extrasynovial tendon portions (particularly the dorsal
      sides) are more wettable than intrasynovial tendons. We also showed that trypsin
      digestion of tendon surfaces increases their wettability. CONCLUSIONS: The
      wettability differences between intrasynovial and extrasynovial canine tendons
      may help to explain known differences in the propensities of these 2 different
      tendon types to form adhesions after surgery.

PMID- 16945717
TI  - Kinematics of the midcarpal and radiocarpal joint in flexion and extension: an in
      vitro study.
AB  - PURPOSE: To apply carpal kinematic analysis using noninvasive medical imaging to
      investigate the midcarpal and radiocarpal contributions to wrist flexion and
      extension in a quasidynamic in vitro model. METHODS: Eight fresh-frozen cadaver
      wrists were scanned with computed tomography in neutral, full flexion, and full
      extension. Body-mass-based local coordinate systems were used to track motion of
      the capitate, lunate, and scaphoid with the radius as a fixed reference. Helical
      axis motion parameters and Euler angles were calculated for flexion and
      extension. RESULTS: Minimal out-of-plane carpal motion was noted with the
      exception of small amounts of ulnar deviation and supination in flexion. Overall
      wrist flexion was 68 degrees +/- 12 degrees and extension was 50 degrees +/- 12
      degrees. In flexion, 75% of wrist motion occurred at the radioscaphoid joint, and
      50% occurred at the radiolunate joint. In extension, 92% of wrist motion occurred
      at the radioscaphoid joint, and 52% occurred at the radiolunate joint. Midcarpal
      flexion/extension between the capitate and scaphoid was 0 degrees +/- 5 degrees
      in extension and 10 degrees +/- 13 degrees in flexion. Midcarpal
      flexion/extension between the capitate and lunate was larger, with 15 degrees +/-
      11 degrees in extension and 22 degrees +/- 19 degrees in flexion. CONCLUSIONS:
      The capitate and scaphoid tend to move together. This results in greater
      flexion/extension for the scaphoid than the lunate at the radiocarpal joint. The
      lunate has greater midcarpal motion between it and the capitate than the scaphoid
      does with the capitate. The engagement between the scaphoid and capitate is
      particularly evident during wrist extension. Out-of-plane motion was primarily
      ulnar deviation at the radiocarpal joint during flexion. These results are
      clinically useful in understanding the consequences of isolated fusions in the
      treatment of wrist instability.

PMID- 16945719
TI  - Closing radial wedge osteotomy for Preiser's disease: a case report.
AB  - A case of Preiser's disease treated with closing radial wedge osteotomy is
      reviewed and the therapeutic effect is reported. A good result was obtained in
      the short term and we believe that this surgical method could become one of the
      choices for surgical treatment to alleviate pain in Preiser's disease.

PMID- 16945718
TI  - Concomitant Kienbock's and Preiser's diseases: a case report.
AB  - Reports of simultaneous carpal avascular necrosis in more than 1 bone are rare.
      This is a report of simultaneous Kienbock's disease and Preiser's disease in a 50
      year-old woman with a remote history of steroid use but without a history of
      trauma or systemic illness.

PMID- 16945720
TI  - Pisotriquetral arthrosis after triquetral malunion: a case report.
AB  - We report a patient with chronic ulnar palmar wrist pain caused by malunion after
      isolated fracture of the triquetrum. Intra-articular malunion of the triquetrum
      body resulted in posttraumatic pisotriquetral arthrosis. The diagnosis was made
      by magnetic resonance imaging, computed tomography, bone scintigraphy, and wrist
      arthroscopy 5 months after the injury. The patient's symptoms were relieved by
      excision of the pisiform.

PMID- 16945721
TI  - Three-dimensional analysis of the ligamentous attachments of the first
      carpometacarpal joint.
AB  - PURPOSE: To show the ligamentous locations and attachments of the first
      carpometacarpal (CMC) joint on a 3-dimensional (3-D) surface model. METHODS: Ten
      fresh-frozen cadaver wrists were used to dissect and identify the first CMC
      ligaments. Their ligamentous attachments and whole bone surfaces were digitized 3
      dimensionally and their areas were calculated. The attachments of each ligament
      were represented in a model combining 3-D computed tomography surfaces overlaid
      by a digitized 3-D surface and also were shown visually by a specific color on 3
      D bone images. The superimposed outlines of the ligamentous attachments on both
      the radial and ulnar base of the first metacarpal (MC) also are described.
      RESULTS: Seven ligaments of the first CMC joint were identified: the dorsoradial
      ligament, the posterior oblique ligament, the superficial anterior oblique
      ligament, the deep anterior oblique ligament, the ulnar collateral ligament, the
      dorsal first MC ulnar base-second MC radial base intermetacarpal ligament, and
      the volar first MC ulnar base-second MC radial base intermetacarpal ligament. The
      detailed locations and areas of the ligamentous attachments of the first CMC
      joint were determined. The average locations of the centroid of the ligamentous
      attachments of the ulnar collateral and the dorsoradial ligaments were located
      ulnovolar and dorsoradial on the first MC base, respectively. CONCLUSIONS: The
      anatomic 3-D attachment sites of the first CMC ligaments were shown qualitatively
      and their areas were quantified. The results of this study improve the knowledge
      and understanding of the normal anatomy and its impact on the mechanics of the
      first CMC joint. This should help in making an accurate assessment of
      radiographic images and treating injuries and degenerative changes in the first
      CMC joint by ligament reconstruction, repair, and arthroscopy.

PMID- 16945722
TI  - Entire flexor carpi radialis tendon harvest for thumb carpometacarpal
      arthroplasty alters wrist kinetics.
AB  - PURPOSE: To investigate the clinical outcome of thumb carpometacarpal
      arthroplasty with entire-thickness flexor carpi radialis (FCR) ligament
      reconstruction and tendon interposition and to investigate the isokinetic wrist
      flexion/extension torque and flexion fatigue strength of the surgically treated
      wrist compared with the nonsurgically treated wrist. METHODS: Thirty-nine
      patients with osteoarthritis who had unilateral thumb carpometacarpal
      arthroplasty with the entire FCR tendon were studied prospectively with a minimum
      follow-up period of 24 months. Preoperative Disabilities of the Arm, Shoulder,
      and Hand (DASH) questionnaire score, grip, pinch, and postoperative DASH score,
      grip, pinch, and Biodex (Shirley, NY) isokinetic wrist flexion/extension torques
      were recorded. The nonsurgically treated extremity served as the control for each
      patient with unilateral ligament reconstruction and tendon interposition. Peak
      torque ratios and fatigue were measured for the control and surgically treated
      extremities with the Biodex. RESULTS: Postoperative DASH scores were 12 +/- 4 and
      were improved significantly from preoperative scores of 43 +/- 4. The surgically
      treated extremity showed a significantly lower wrist flexion-to-extension peak
      torque ratio than the control extremity. The control extremity had 2.5 times
      greater wrist flexion fatigue resistance than the surgically treated side. After
      surgery the surgically treated extremity had significantly improved grip strength
      and thumb-index tip pinch compared with the preoperative status. CONCLUSIONS: Our
      data show conclusively that wrist flexion extension torque ratio decreases and
      wrist flexion fatigue resistance decreases when the entire FCR tendon is
      harvested even though the final outcome is favorable and uniformly based on
      traditional DASH, grip, and pinch scores.

PMID- 16945724
TI  - The effect of the epiphyseal growth plate on the length of the first metacarpal
      in triphalangeal thumb.
AB  - PURPOSE: Triphalangeal thumb is characterized as a congenital difference of the
      thumb with an extra phalanx. Additional thumb length is attributed mostly to the
      extra phalanx. The influence of the epiphyseal plate positions on growth in
      congenital hand anomalies is unclear. The purpose of this article was to compare
      the length of the first metacarpal in triphalangeal thumbs with the length of the
      same bone in normal thumbs and to investigate the influence of the often aberrant
      metacarpal epiphyseal plates on the length of the triphalangeal thumb metacarpal
      during growth. METHODS: The positions of the epiphyseal plate and the relative
      length of the first metacarpal were examined retrospectively in 37 patients with
      triphalangeal thumb. Ratios of the measurements were calculated (metacarpal
      II/metacarpal I) and compared with a normal population. Subjects were divided
      into 3 groups based on the position of the epiphyseal plate (double, proximal,
      distal). RESULTS: The distally placed growth plate was the most common variety,
      present in 22 of patients, followed by the proximal position in 14, and double
      epiphyseal plates in 6. All ratios of patients with triphalangeal thumb were
      significantly smaller than those of a normal population, indicating a longer
      first metacarpal in this condition. First metacarpals in triphalangeal thumb with
      double epiphyses grew disproportionately more than those of a normal population,
      whereas those with distal epiphyses grew disproportionately less than normal.
      First metacarpals with proximal epiphyses grew at the same rate as normal first
      metacarpals. CONCLUSIONS: In this study population the most common growth plate
      location was distal whereas the most common location in the normal population is
      proximal. The different positions of the epiphyseal plates correlate with growth
      differences in patients with triphalangeal thumb.

PMID- 16945723
TI  - Radial longitudinal deficiency: the incidence of associated medical and
      musculoskeletal conditions.
AB  - PURPOSE: Radial longitudinal deficiency (RLD) is associated with certain
      syndromes and medical and musculoskeletal conditions. The purpose of this
      investigation was to evaluate the incidence of these conditions with RLD.
      METHODS: A comprehensive chart review identified patients with RLD and a complete
      medical record. These charts were evaluated for the presence of associated
      medical and musculoskeletal conditions and biographic information on gestation,
      delivery, and family history. RESULTS: A total of 164 patients with 245 affected
      extremities were identified; 138 patients had radius abnormalities and 26
      patients had isolated thumb hypoplasia. Twenty-five patients had thrombocytopenia
      absent radius syndrome; 22 patients had vertebral, anal, cardiac,
      tracheoesophageal, renal, and limb abnormalities association; 7 patients had Holt
      Oram syndrome; and 1 patient had Fanconi anemia. There were 32 patients with
      cardiac abnormalities and 60 patients with spinal or lower-extremity
      musculoskeletal abnormalities. The percentage of patients with associated
      abnormalities increased with an increasing severity of RLD. One hundred two of
      the 138 patients with types I through V RLD had associated medical or
      musculoskeletal abnormalities. In contrast, only 9 of 26 patients with an
      isolated thumb hypoplasia (type 0 RLD) had associated abnormalities. CONCLUSIONS:
      The high incidence of associated medical and musculoskeletal abnormalities in
      patients with RLD emphasizes the importance of a complete assessment including a
      complete musculoskeletal examination, cardiac auscultation, complete blood count,
      echocardiogram, renal ultrasound, and spinal radiographs. Although approximately
      one third of patients in this investigation had a syndrome commonly associated
      with RLD, most patients with RLD types I through V had an additional medical or
      musculoskeletal anomaly. Patients with type 0 RLD were less likely to have
      comorbidities.

PMID- 16945725
TI  - Surgical treatment for a congenitally stiff metacarpophalangeal joint of the
      small finger: report of four cases.
AB  - We report 4 cases of a congenitally stiff metacarpophalangeal joint of the small
      finger that were treated satisfactorily with surgical release.

PMID- 16945726
TI  - An unusual presentation of methotrexate-induced B-cell lymphoma of the
      metacarpophalangeal joint: a case report and literature review.
AB  - We report a unusual presentation of B-cell lymphoma in the chronically inflamed
      synovium of a 64-year-old man with an 18-year history of rheumatoid arthritis
      that was treated with methotrexate.

PMID- 16945727
TI  - Solitary plasmocytoma of the distal humerus.
AB  - A patient presented with chronic shoulder pain from a rare plasmocytoma in the
      distal humerus that resolved following a pathologic fracture. Staged
      reconstruction of the elbow after resection of the tumor in the distal humerus
      resulted in resolution of the patient's elbow and shoulder symptoms.

PMID- 16945728
TI  - Upper-extremity mucormycosis infections in immunocompetent patients.
AB  - PURPOSE: Mucormycosis can produce an aggressive and sometimes fatal soft tissue
      infection seen most commonly in immunocompromised individuals. Eradication
      consists of surgical resection and antifungal chemotherapy. Knowledge regarding
      infectious mucormycosis in the upper extremity has been limited to case reports
      involving mainly immunocompromised individuals. The purpose of this study was to
      identify risk factors for the development of mucormycosis infections within the
      upper extremity in immunocompetent individuals and to evaluate the effectiveness
      of the present therapies. METHODS: A 12-year retrospective review of all fungal
      infections involving the upper extremity was conducted in our institution. Seven
      immunocompetent patients with infectious cutaneous mucormycosis of the upper
      extremity were identified from 223 primary upper-extremity fungal infections.
      RESULTS: In the 7 patients 3 infections resulted from heavy soil contamination
      after motor vehicle collisions and 4 resulted from conveyor belt injuries in
      agricultural facilities. All patients had considerable upper-extremity soft
      tissue loss and 6 of the 7 patients had upper-extremity fractures or
      dislocations. Patients had an average of 10 surgical debridements. Four
      infections resulted in amputations: 1 partial hand amputation, 1 below the elbow,
      1 above the elbow, and 1 at the glenohumeral joint. CONCLUSIONS: Mucormycosis can
      produce limb-threatening infections in an immunocompetent host. Hand surgeons
      must have suspicion of such infections in patients with grossly contaminated open
      wounds.

PMID- 16945729
TI  - Madelung's deformity: treatment with radial osteotomy and insertion of a
      trapezoidal wedge.
AB  - This article describes a modification of the double-osteotomy radial technique
      that has been described previously and summarizes our clinical experience with
      this method in 4 female patients. All patients had improvement in functional
      motion and were satisfied with the improved appearance of their wrist after
      surgery.

PMID- 16945730
TI  - Giant-cell tumors of the carpus.
AB  - Giant cell tumor (GCT) of bone is a rare, benign tumor with some aggressive
      characteristics such as a high recurrence rate. The tumor usually occurs in the
      distal radius although it has been reported in the carpus. We reviewed 63
      manuscripts published from 1935 to 2005 and report on the treatment of GCT of
      carpal bone in 29 cases. Intralesional procedures, such as curettage, were
      associated with a high incidence of recurrence (24%), whereas cases treated with
      an excisional procedure did not recur.

PMID- 16945731
TI  - Homodigital antegrade-flow neurovascular pedicle flaps for sensate reconstruction
      of fingertip amputation injuries.
AB  - Fingertip amputations through the distal 50% of the nail matrix usually create a
      finger that is best served by maintaining length. When the amputation is more
      proximal than this, revision with ablation of the small residual nail unit may
      provide greater overall patient satisfaction. When amputations in the distal 50%
      of the nail matrix are transverse or short oblique in orientation, a flap of some
      kind is needed to restore the contact surface of the pulp. Many alternative
      reconstructive strategies are possible but have inherent limitations that detract
      from the quality of the final result. Inadequate padding, lack of sensibility,
      excessive tension, hook nail deformity, poor durability, and donor site morbidity
      are but some of the considerations. Although not a panacea for all distal
      fingertip amputations, the antegrade-flow homodigital neurovascular pedicle flap
      offers a good ratio of advantages to disadvantages. As with all flaps, knowledge
      and execution of the details largely determine the outcome.

PMID- 16945732
TI  - 2004-2005 Sterling Bunnell Traveling Fellowship report.
AB  - The Bunnell Traveling Fellowship was established in 1982 with the purpose of
      sponsoring a young hand surgeon in the development of national and international
      relationships that contribute to his/her pursuit of higher learning and that
      foster the principles of scholarship of the American Society for Surgery of the
      Hand. I was fortunate to be selected as the 24th Sterling Bunnell Fellow, and I
      had the opportunity to follow in the footsteps of the 23 former fellows. In
      Bunnell's Surgery of the Hand, Fourth Edition (Boyes JH, ed. Philadelphia,
      Lippincott; 1964:561-567), a man with a brachial plexus injury was described. The
      recommended treatment was shoulder arthrodesis and transhumeral amputation,
      followed by fitting of an above-elbow prosthesis. Sterling Bunnell has been
      quoted as saying, "To someone who has nothing, a little is a lot." Nowhere in the
      field of hand surgery is this more true than in patients with brachial plexus
      injuries. The theme and purpose of my traveling fellowship was to evaluate the
      status and advances of adult brachial plexus surgery throughout the world, to
      determine the utility of the contralateral C7 nerve transfer, to evaluate the
      optimal reconstruction of grasp, and finally to determine the philosophies of
      experts around the world regarding the treatment of these patients.

PMID- 16945733
TI  - Osseointegration and mechanical stability of pyrocarbon and titanium hand
      implants in a load-bearing in vivo model for small joint arthroplasty.

PMID- 16945735
TI  - Rare case of double inlet left ventricle: functional and anatomic information
      provided by adenosine Tc-99m sestamibi SPECT.

PMID- 16945736
TI  - Nuclear cardiology: where are we and where are we going?

PMID- 16945737
TI  - Technetium tetrofosmin myocardial perfusion imaging in women.

PMID- 16945738
TI  - Coronary computed tomographic angiography: competitive or complementary?

PMID- 16945739
TI  - Asymptomatic patients with diabetes mellitus should be screened for coronary
      artery disease.

PMID- 16945740
TI  - Asymptomatic patients with diabetes mellitus should not be screened for coronary
      artery disease.

PMID- 16945741
TI  - Direct comparison of adenosine and adenosine 5'-triphosphate as pharmacologic
      stress agents in conjunction with Tl-201 SPECT: Hemodynamic response, myocardial
      tracer uptake, and size of perfusion defects in the same subjects.
AB  - BACKGROUND: Adenosine 5'-triphosphate (ATP), a potent and inexpensive coronary
      vasodilator, was introduced as a pharmacologic stress agent for thallium 201
      single photon emission computed tomography (SPECT). However, there has been no
      direct comparison of ATP and adenosine as myocardial stressors in the same
      subjects. METHODS AND RESULTS: Thirty-six patients underwent consecutive Tl-201
      SPECT imaging with adenosine and ATP in a randomly assigned order. There were no
      changes in clinical status and no invasive procedures were performed between the
      two tests. The hemodynamic response and side effects were monitored, and
      myocardial tracer uptake was assessed by use of a visual grading system and
      quantitative analysis via a CEqual map. The hemodynamic changes and adverse
      effects did not differ significantly between the two groups. There were no
      changes in the detection of any perfusion defect on a per-subject basis, except
      in one. The exact agreement rate for the visual grading of the myocardial tracer
      uptake was 84.8%. However, the average extent of the perfusion defect and the
      severity score were higher with adenosine. CONCLUSION: The hemodynamic changes
      and the degree of myocardial uptake were similar between the adenosine and ATP
      infusion. However, quantitative analysis by use of a CEqual map revealed smaller
      perfusion defects and lower severity scores in subjects undergoing Tl-201 SPECT
      with ATP.

PMID- 16945742
TI  - Accuracy of stress Tc-99m tetrofosmin myocardial perfusion tomography for the
      diagnosis and localization of coronary artery disease in women.
AB  - BACKGROUND: Earlier studies have suggested a modest accuracy of stress thallium
      201 myocardial perfusion imaging (MPI) for the diagnosis of coronary artery
      disease (CAD) in women. The accuracy of stress MPI with technetium 99m
      tetrofosmin has not been studied in women. The aim of this study was to assess
      the accuracy of stress Tc-99m tetrofosmin MPI for the diagnosis and localization
      of CAD in women. METHODS AND RESULTS: We studied 88 women who underwent exercise
      or dobutamine stress Tc-99m tetrofosmin tomography and coronary angiography
      within 3 months. Significant CAD was defined as a stenosis 50% or greater in
      diameter in at least 1 major epicardial coronary artery. Myocardial perfusion
      abnormalities were detected in 44 of 53 patients with significant CAD and in 7 of
      35 patients without significant CAD (overall sensitivity, 83% [95% confidence
      interval (CI), 73%-93%]; specificity, 80% [95% CI, 67%-93%]; and accuracy, 82%
      [95% CI, 74%-90%]). The sensitivity was 72% (18/25) in patients with single
      vessel CAD and 93% (26/28) in patients with multivessel CAD. Perfusion
      abnormalities were detected in 2 or more vascular distributions in 20 of 28
      patients with multivessel CAD and in 4 of 60 patients without multivessel CAD
      (sensitivity for the identification of multivessel CAD, 71% [95% CI, 55%-88%];
      specificity, 93% [95% CI, 86%-98%]; and accuracy, 86% [95% CI, 79%-93%]). The
      sensitivity, specificity, and accuracy were 82%, 84%, and 83%, respectively, for
      the diagnosis of CAD in the left anterior descending artery; 77%, 84%, and 81%,
      respectively, for CAD in the right coronary artery; and 74%, 80%, and 78%,
      respectively, for CAD in the left circumflex artery. CONCLUSION: Stress Tc-99m
      tetrofosmin MPI is an accurate noninvasive technique for the diagnosis and
      localization of CAD in women.

PMID- 16945743
TI  - Do risk factors influence the diagnostic accuracy of noninvasive coronary
      angiography with multislice computed tomography?
AB  - BACKGROUND: Multislice computed tomography (MSCT) is a relatively new noninvasive
      imaging modality in the evaluation of patients with suspected coronary artery
      disease (CAD). Whether diagnostic accuracy is influenced by gender or risk
      factors for CAD is currently unknown and was evaluated in this study. METHODS AND
      RESULTS: In 197 patients (171 men and 26 women; mean age, 60 +/- 11 years) 16
      slice MSCT was performed and compared with invasive coronary angiography at 2
      different centers (Leiden and Rotterdam, The Netherlands). Diagnostic accuracy
      for the detection of 50% luminal narrowing or greater was calculated for all
      patients combined, as well as for patients with known versus suspected CAD. In
      addition, diagnostic accuracy was determined in men versus women and in different
      subsets of patients based on the presence of risk factors for CAD including
      hypertension, type 2 diabetes mellitus, hypercholesterolemia, and obesity. Only
      segments with a diameter of 2.0 mm or greater were evaluated, whereas smaller
      segments and stents were excluded from the analysis. Overall, a sensitivity and
      specificity of 99% and 86%, respectively, on a patient level were demonstrated,
      with corresponding positive and negative predictive values of 95% and 96%,
      respectively. Similar values were observed in the different subsets of patients,
      with no statistical differences. CONCLUSION: These findings confirm the high
      diagnostic accuracy of MSCT, regardless of gender or risk factors.

PMID- 16945744
TI  - Simplified normal limits and automated quantitative assessment for attenuation
      corrected myocardial perfusion SPECT.
AB  - BACKGROUND: We aimed to compare normal limits and the detection of coronary
      artery disease (CAD) with attenuation-corrected (AC) and non-attenuation
      corrected (NC) myocardial perfusion single photon emission computed tomography
      (MPS) by use of a recently improved automated quantification technique. METHODS
      AND RESULTS: We acquired 415 rest/stress technetium 99m MPS studies on a Vertex
      dual-detector camera with a gadolinium 153 line source (Vantage Pro). Gender
      specific NC, AC, and gender-combined AC normal limits were created from
      rest/stress images of 50 women and 50 men with a low likelihood of CAD (< 5%) and
      a median body mass index (BMI) of 30 kg/m2 in each gender group. BMI-specific
      normal limits (< 30 kg/m2 and > or = 30 kg/m2) were also compared. Total
      perfusion deficit and 17-segment summed scores in 174 patients were compared with
      angiography, and normalcy rates were established from 141 studies of low
      likelihood patients. There were no differences between low-BMI and high-BMI
      normal limits for AC or NC studies. Male and female normal limits differed in 12
      of 17 segments for NC stress studies and in 3 of 17 segments for AC stress
      studies (P < .01). The sensitivity, specificity, and normalcy rates for stenoses
      with 70% narrowing or greater were 89%, 73%, and 91%, respectively, for NC
      studies and 87%, 80%, and 95%, respectively, for AC studies (P = not
      significant). CONCLUSION: Automated detection of CAD by AC and NC MPS
      demonstrated similar sensitivity, specificity, and normalcy rates. Some gender
      differences were noted for AC normal limits.

PMID- 16945745
TI  - Left ventricular shape index assessed by gated stress myocardial perfusion SPECT:
      initial description of a new variable.
AB  - BACKGROUND: Ventricular remodeling is predictive of congestive heart failure
      (CHF). We aimed to automatically quantify a new myocardial shape variable on
      gated myocardial perfusion single photon emission computed tomography (SPECT)
      (MPS) and to evaluate the association of this new SPECT parameter with the risk
      of hospitalization for CHF. METHODS AND RESULTS: A computer algorithm was used to
      measure the 3-dimensional (3D) left ventricular (LV) shape index (LVSI), derived
      as the ratio of maximum 3D short- and long-axis LV dimensions, for end systole
      and end diastole. LVSI normal limits were obtained from stress technetium 99m
      sestamibi MPS images of 186 patients (60% of whom were men) (control subjects)
      with a low likelihood of CAD (< 5%). These limits were tested in a consecutive
      series of 93 inpatients (85% of whom were men) having MPS less than 1 week after
      hospitalization, of whom 25 were hospitalized for CHF exacerbation. Variables
      associated with CHF hospitalization were tested by receiver operating
      characteristic curve and multivariate logistic regression analyses. LVSI
      repeatability was assessed in 52 patients with ischemic cardiomyopathy who had
      sequential stress MPS within 60 days after the initial MPS without clinical
      events in the interval between MPS studies. Control subjects had lower end
      systolic and end-diastolic LVSIs compared with patients with CHF and those
      without CHF (P < .001). Receiver operating characteristic curve areas for the
      prediction of hospitalization as a result of CHF were similar for LV ejection
      fraction and end-systolic LVSI. End-systolic and end-diastolic LVSIs were
      independent predictors of CHF hospitalization by multivariate analysis; however,
      end-systolic LVSI had the greatest added value among all tested variables.
      Repeatability was excellent for both end-systolic LVSI (R2 = 0.85, P < .0001) and
      end-diastolic LVSI (R2 = 0.82, P < .001). CONCLUSION: LVSI is a promising new 3D
      variable derived automatically from gated MPS providing highly repeatable
      ventricular shape assessment. Preliminary findings suggest that LVSI might have
      clinical implications in patients with CHF.

PMID- 16945746
TI  - Regional heterogeneity of resting perfusion in hypertrophic cardiomyopathy is
      related to delayed contrast enhancement but not to systolic function: a PET and
      MRI study.
AB  - BACKGROUND: Regional differences in resting myocardial blood flow (MBF) have been
      observed in patients with hypertrophic cardiomyopathy (HCM), but their
      determinants are currently unknown. This study verifies whether MBF at rest in
      HCM is related to delayed contrast enhancement (DCE) or regional systolic
      function (or both) as determined by magnetic resonance imaging. METHODS AND
      RESULTS: Fourteen patients with HCM were studied. MBF was measured with positron
      emission tomography by use of oxygen 15-labeled water. DCE and tissue tagging, to
      calculate end-systolic circumferential shortening (Ecc), were obtained with
      magnetic resonance imaging. The mean resting MBF was 0.78 +/- 0.19 mL x min(-1) x
      mL(-1), and there was a trend toward reduced MBF in the septum (0.72 +/- 0.11 mL
      x min(-1) x mL(-1)) compared with that in the lateral wall (0.84 +/- 0.29 mL x
      min(-1) x mL(-1)) (P = .092). The distribution patterns of DCE and Ecc were both
      heterogeneous, displaying significantly increased enhancement and impaired
      regional systolic function in the hypertrophic septum compared with the lateral
      wall (both P < .001). Resting MBF was inversely related to the extent of DCE (r =
      -0.30, P < .001), whereas MBF was not significantly related to Ecc (r = -0.15, P
      = .072). CONCLUSIONS: Regional heterogeneity of resting perfusion in HCM is
      related to the extent of DCE but not to regional systolic function.

PMID- 16945748
TI  - Comparison among tomographic radionuclide ventriculography algorithms for
      computing left and right ventricular normal limits.
AB  - BACKGROUND: Various algorithms have been developed to compute right ventricular
      (RV) and left ventricular (LV) end-diastolic volumes, end-systolic volumes, and
      ejection fractions (EF) from tomographic radionuclide ventriculography (TRV). The
      aims of this investigation were to establish sex-specific normal limits, to
      determine whether different algorithms produce the same normal values, and to
      compare TRV normal limits vs for magnetic resonance imaging values in the
      literature. METHODS: Fifty-one healthy volunteers (29 men, 22 women) were studied
      prospectively. All subjects had normal electrocardiograms and echocardiographic
      examinations, and underwent both planar radionuclide ventriculography and TRV.
      Four algorithms were used to process TRV data. RESULTS: Normal limits for most
      functional parameters differed significantly from one algorithm to another.
      Volumes were greater in men, but no statistically significant differences were
      found between men and women for LV EF or RV EF values for any method. Normal LV
      and RV EF and volumes were largely consistent with the literature for cardiac
      magnetic resonance imaging. CONCLUSIONS: Ventricular measurements differ
      significantly among TRV algorithms. Therefore, it is important to apply sex
      specific normal limits that are specific to a given TRV algorithm in interpreting
      LV and RV EF and volume measurements for each patient.

PMID- 16945747
TI  - Differences in left ventricular ejection fraction and volumes measured at rest
      and poststress by gated sestamibi SPECT.
AB  - BACKGROUND: Some studies suggested that the poststress left ventricle ejection
      fraction (LV EF) is lower than rest LV EF in patients with stress-induced
      ischemia. METHODS AND RESULTS: By using a 2-day protocol and 30 mCi Tc-99m
      sestamibi, LV EF, end-systolic volume (ESV), and end-diastolic volume (EDV) were
      measured with gated SPECT. Of 99 eligible patients, 91 had technically adequate
      studies. Poststress LV EF minus rest LV EF was defined as DeltaLV EF. DeltaEDV
      and DeltaESV were similarly defined. Rest and poststress LV EF (r = 0.89), EDV (r
      = 0.78), and ESV (r = 0.93) were highly correlated (P <.001). Rest LV EF, EDV,
      and ESV were not significantly different between patients with and without stress
      induced ischemia. DeltaLV EF was significantly lower in patients with stress
      induced ischemia (-3.5% +/- 4.5% vs -1.1% +/- 4.7%, P = .02). Mean LV EF
      poststress in ischemic patients was 55.0% +/- 10.5% vs 61.2% +/- 10.0% in
      nonischemic patients (P = .008). However, only 1 patient (3%) with ischemia had
      DeltaLV EF that exceeded the 95% confidence limit of DeltaLV EF for normal
      patients. Ischemia was significantly associated with increased DeltaEDV and
      DeltaESV (P < .01). CONCLUSIONS: Stress-induced ischemia is associated with
      poststress reduction in LV EF and increased poststress EDV and ESV. However, the
      effect of ischemia on the difference between poststress and rest EF measurements
      is modest and rarely exceeds the confidence limits in normal patients undergoing
      2-day protocols. In most patients, poststress LV EF is an accurate reflection of
      rest LV EF.

PMID- 16945750
TI  - Advances in detection and characterization of atherosclerosis using contrast
      agents targeting the macrophage.

PMID- 16945749
TI  - Gated myocardial perfusion single photon emission computed tomography in the
      clinical outcomes utilizing revascularization and aggressive drug evaluation
      (COURAGE) trial, Veterans Administration Cooperative study no. 424.
AB  - BACKGROUND: Stress gated myocardial perfusion single photon emission computed
      tomography (gSPECT) is increasingly used before and after intercurrent
      therapeutic intervention and is the basis for ongoing evaluation in the
      Department of Veterans Affairs clinical outcomes utilizing revascularization and
      aggressive drug evaluation (COURAGE) trial. METHODS AND RESULTS: The COURAGE
      trial is a North American multicenter randomized clinical trial that enrolled
      2287 patients to aggressive medical therapy vs percutaneous coronary intervention
      plus aggressive medical therapy. Three COURAGE nuclear substudies have been
      designed. The goals of substudy 0 are to examine the diagnostic accuracy of the
      extent and severity of inducible ischemia at baseline in COURAGE patients
      compared with patient symptoms and quantitative coronary angiography and to
      explore the relationship between inducible ischemia and the benefit from
      revascularization when added to medical therapy. Substudy 1 will correlate the
      extent and severity of provocative ischemia with the frequency, quality, and
      instability of recurrent symptoms in postcatheterization patients. Substudy 2 (n
      = 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months
      after therapeutic intervention. Together, these nuclear substudies will evaluate
      the role of gSPECT to determine the effectiveness of aggressive risk-factor
      modifications, lifestyle interventions, and anti-ischemic medical therapies with
      or without revascularization in reducing patients' ischemic burdens. CONCLUSIONS:
      The unfolding of evidence on the application of gSPECT in trials such as COURAGE
      defines a new era for nuclear cardiology. We hope the evidence that emerges from
      the COURAGE trial will further establish the role of nuclear imaging in the
      evidence-based management of patients with stable coronary disease.

PMID- 16945751
TI  - Clinical value of carotid intima-media thickness testing.
AB  - Carotid intima-media thickness (CIMT) testing is recognized as a valid method for
      the noninvasive assessment of atherosclerosis. In addition to its association
      with known cardiovascular risk factors and both prevalent and incident coronary
      heart disease, the rate of CIMT progression is directly related to the risk for
      future cardiovascular events. Subsequently, CIMT has been a valuable research
      tool in clinical trials in the assessment of therapeutic agents directed against
      atherosclerosis. An overview of CIMT testing including its precise measurement,
      establishment as a surrogate for atherosclerosis by epidemiologic trials, role in
      clinical trials, and potential applications in both primary and secondary
      coronary heart disease prevention is presented.

PMID- 16945752
TI  - Demonstration of an ectopic mediastinal parathyroid adenoma on Tc-99m sestamibi
      myocardial perfusion scintigraphy.

PMID- 16945753
TI  - Tc-99m sestamibi myocardial perfusion imaging after undisclosed I-131 therapy.

PMID- 16945754
TI  - Increased right ventricular uptake on stress SPECT myocardial perfusion images in
      a patient with severe coronary artery disease.

PMID- 16945755
TI  - Bilateral photopenic areas in the lungs on SPECT imaging.

PMID- 16945756
TI  - Practical points for nuclear cardiology.

PMID- 16945759
TI  - Systemic activation and vascular infiltration of neutrophils with term labor.
AB  - OBJECTIVE: The purpose of the current study was to determine if neutrophils
      infiltrate maternal systemic vascular tissue at the time of term labor. METHODS:
      Subcutaneous fat biopsies were obtained at cesarean delivery or abdominal surgery
      from laboring women (n = 5), non-laboring women (n = 5), and normal non-pregnant
      women (n = 5). Immunohistochemical staining was performed for CD66b, a neutrophil
      antigen, and intercellular adhesion molecule-1 (ICAM-1; CD54), an endothelial
      cell adhesion molecule for neutrophils. Vessels (10 to 200 microm) were analyzed
      for intensity of staining and percentage of vessels with staining. RESULTS: CD66b
      staining intensity was significantly greater for laboring women at term than for
      non-laboring women at term or for normal non-pregnant women (1.3 +/- 0.3 versus
      0.2 +/- 0.1 versus 0.2 +/- 0.1, respectively, P < .01). Laboring women had
      significantly more vessels with staining for CD66b (79 +/- 4 versus 24 +/- 8
      versus 19 +/- 6%, P < .001), more vessels with neutrophils adhered and flattened
      to endothelium (67 +/- 3 versus 16 +/- 7 versus 12 +/- 4%, P < .001), more
      vessels with neutrophils in the intima (30 +/- 6 versus 5 +/- 2 versus 2 +/- 1%,
      P < .05), and a greater number of neutrophils per vessel (5.4 +/- 1.1 versus 1.7
      +/- 0.5 versus 1.2 +/- 0.3, P < .01) as compared to non-laboring or normal non
      pregnant women. ICAM-1 staining was present in the endothelium of all groups,
      with no difference in staining intensity or percent of vessels stained. Between
      86% to 96% of vessels stained for ICAM-1. Laboring patients had numerous
      leukocytes stained for ICAM-1 in their vessels. CONCLUSION: This study
      demonstrates that neutrophils infiltrate maternal systemic vascular tissue at the
      time of term labor. Neutrophils were flattened and adhered to endothelium and
      infiltrated into the intimal space.

PMID- 16945760
TI  - Has genetic profiling finally come of age in NSCLC?

PMID- 16945761
TI  - Keynote comment: deliberations of a born-again cancer immunotherapist.

PMID- 16945762
TI  - Adjuvant chemotherapy for resected non-small-cell lung cancer--ANITA takes the
      stage.

PMID- 16945763
TI  - Don't forget survival, please...

PMID- 16945764
TI  - Radiotherapy might not be the answer in Africa.

PMID- 16945766
TI  - Adjuvant vinorelbine plus cisplatin versus observation in patients with
      completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine
      International Trialist Association [ANITA]): a randomised controlled trial.
AB  - BACKGROUND: Whether adjuvant chemotherapy improves survival of patients with non
      small-cell lung cancer (NSCLC) is not known. We aimed to compare the effect of
      adjuvant vinorelbine plus cisplatin versus observation on survival in patients
      with completely resected NSCLC. METHODS: 840 patients with stage IB-IIIA NSCLC
      from 101 centres in 14 countries were randomly assigned to observation (n=433) or
      to 30 mg/m(2) vinorelbine plus 100 mg/m(2) cisplatin (n=407). Postoperative
      radiotherapy was not mandatory and was undertaken according to every centre's
      policy. The primary endpoint was overall survival. Analysis was by intention to
      treat. This trial is registered as an International Standard Randomised
      Controlled Trial, number ISRCTN95053737. FINDINGS: 367 patients in the
      chemotherapy group and 431 in the control group received their assigned
      treatment. 301 (36%) patients had stage IB disease, 203 (24%) had stage II
      disease, and 325 (39%) had stage IIIA disease. Tolerance to chemotherapy mainly
      included neutropenia in 335 (92%) patients and febrile neutropenia in 34 (9%);
      seven (2%) toxic deaths were also recorded. Compliance was greater with cisplatin
      than with vinorelbine (median dose intensity 89% [range 17-108] vs 59% [17-100]).
      After a median follow-up of 76 months (range 43-116), median survival was 65.7
      months (95% CI 47.9-88.5) in the chemotherapy group and 43.7 (35.7-52.3) months
      in the observation group. Adjusted risk for death was significantly reduced in
      patients assigned chemotherapy compared with controls (hazard ratio 0.80 [95% CI
      0.66-0.96]; p=0.017). Overall survival at 5 years with chemotherapy improved by
      8.6%, which was maintained at 7 years (8.4%). INTERPRETATION: Adjuvant
      vinorelbine plus cisplatin extends survival in patients with completely resected
      NSCLC, better defining indication of adjuvant chemotherapy.

PMID- 16945767
TI  - Staging of carcinoid tumours with 18F-DOPA PET: a prospective, diagnostic
      accuracy study.
AB  - BACKGROUND: To assess individual treatment options for patients with carcinoid
      tumours, accurate knowledge of tumour localisation is essential. We aimed to test
      the diagnostic sensitivity of 6-[fluoride-18]fluoro-levodopa ((18)F-DOPA PET),
      compared with conventional imaging methods, in patients with carcinoid tumours.
      METHODS: In a prospective, single-centre, diagnostic accuracy study, (18)F-DOPA
      PET with carbidopa pretreatment was compared with somatostatin-receptor
      scintigraphy (SRS), CT, and combined SRS and CT in 53 patients with a metastatic
      carcinoid tumour. The performance of all imaging methods was analysed for
      individual patients, for eight body regions, and for the detection of individual
      lesions. PET and CT images were fused to improve localisation. To produce a
      composite reference standard, we used cytological and histological findings; all
      imaging tests, including secondary assessments for newly found lesions; follow
      up; and biochemical data. Sensitivities were calculated and compared. FINDINGS:
      In patient-based analysis, we recorded sensitivities of 100% (95% CI 93-100) for
      (18)F-DOPA-PET, 92% (82-98) for SRS, 87% (75-95) for CT, and 96% (87-100) for
      combined SRS and CT (p=0.45 for (18)F-DOPA PET vs combined SRS and CT). However,
      (18)F-DOPA PET detected more lesions, more positive regions, and more lesions per
      region than combined SRS and CT. In region-based analysis, sensitivity of (18)F
      DOPA PET was 95% (90-98) versus 66% (57-74) for SRS, 57% (48-66) for CT, and 79%
      (70-86) for combined SRS and CT (p=0.0001, PET vs combined SRS and CT). In
      individual-lesion analysis, corresponding sensitivities were 96% (95-98), 46% (43
      50), 54% (51-58), and 65% (62-69; p<0.0001 for PET vs combined SRS and CT).
      INTERPRETATION: If the improved tumour localisation seen with (18)F-DOPA-PET
      compared with conventional imaging is confirmed in future studies, this imaging
      method could replace use of SRS, help improve prediction of prognosis, and be
      used to assess patients' response to treatment for carcinoid tumours.

PMID- 16945768
TI  - Chronic kidney disease after nephrectomy in patients with renal cortical tumours:
      a retrospective cohort study.
AB  - BACKGROUND: Chronic kidney disease is a graded and independent risk factor for
      substantial comorbidity and death. We aimed to examine new onset of chronic
      kidney disease in patients with small, renal cortical tumours undergoing radical
      or partial nephrectomy. METHODS: We did a retrospective cohort study of 662
      patients with a normal concentration of serum creatinine and two healthy kidneys
      undergoing elective partial or radical nephrectomy for a solitary, renal cortical
      tumour (</=4 cm) between 1989 and 2005 at a referral cancer centre. Glomerular
      filtration rate (GFR) was estimated with the abbreviated Modification in Diet and
      Renal Disease Study equation. Separate analysis was undertaken, with chronic
      kidney disease defined as GFR lower than 60 mL/min per 1.73 m(2) and GFR lower
      than 45 mL/min per 1.73 m(2). FINDINGS: 171 (26%) patients had pre-existing
      chronic kidney disease before surgery. After surgery, the 3-year probability of
      freedom from new onset of GFR lower than 60 mL/min per 1.73 m(2) was 80% (95% CI
      73-85) after partial nephrectomy and 35% (28-43; p<0.0001) after radical
      nephrectomy; corresponding values for GFRs lower than 45 mL/min per 1.73 m(2)
      were 95% (91-98) and 64% (56-70; p<0.0001), respectively. Multivariable analysis
      showed that radical nephrectomy remained an independent risk factor for patients
      developing new onset of GFR lower than 60 mL/min per 1.73 m(2) (hazard ratio 3.82
      [95% CI 2.75-5.32]) and 45 mL/min per 1.73 m(2) (11.8 [6.24-22.4]; both
      p<0.0001). INTERPRETATION: Because the baseline kidney function of patients with
      renal cortical tumours is lower than previously thought, accurate assessment of
      kidney function is essential before surgery. Radical nephrectomy is a significant
      risk factor for the development of chronic kidney disease and might no longer be
      regarded as the gold standard treatment for small, renal cortical tumours.

PMID- 16945770
TI  - Laryngeal preservation in head and neck cancer: multidisciplinary approach.
AB  - Since the first total laryngectomy was undertaken, efforts have been made to
      avoid removing the entire larynx. For a long time, partial surgery and
      radiotherapy were the only options that could preserve the larynx. Development of
      active chemotherapy regimens has prompted an era of intensive clinical research.
      Induction chemotherapy followed by radiotherapy in patients with objective
      responses has been shown to allow conservation of the larynx in nearly two-thirds
      of individuals, without any effect on survival; concurrent chemoradiotherapy also
      provides high rates of laryngeal preservation, again without affecting survival;
      and induction chemotherapy followed by concurrent chemoradiotherapy is under
      investigation. In the meantime, partial open surgery and endoscopic carbon
      dioxide laser procedures are feasible in selected moderately advanced
      laryngopharyngeal cancers as an alternative to destructive surgery. Altered
      fractionation radiotherapy can also be used in management of these tumours, and
      targeted treatments have opened a new area of clinical research. Findings of
      basic research and modern imaging should provide useful approaches for selection
      of patients for various strategies.

PMID- 16945769
TI  - Response rate or time to progression as predictors of survival in trials of
      metastatic colorectal cancer or non-small-cell lung cancer: a meta-analysis.
AB  - BACKGROUND: The duration and cost of cancer clinical trials could be reduced if a
      surrogate endpoint were used in place of survival. We did a meta-analysis to
      assess the extent to which two surrogates, tumour response and time to
      progression, are predictive of mortality in metastatic colorectal cancer and non
      small-cell lung cancer. METHODS: Summary data (median time to progression,
      proportion of patients responding to treatment, and median overall survival) from
      randomised trials of first-line treatment in colorectal cancer (146 trials) and
      lung cancer (191 trials) were identified. Data were extracted and analysed by
      linear regression. We used prediction bands for trials with 250, 500, and 750
      patients to identify the surrogate threshold effect that would predict a
      significant difference in survival. FINDINGS: Response to treatment and time to
      progression correlated with improvement in survival for both lung cancer
      (p<0.0001 and p=0.0003, respectively) and colorectal cancer (p<0.0001 for both).
      To predict a significant survival gain in colorectal cancer trials, an
      improvement of 20% in the number of patients responding to treatment was required
      in trials with 750 patients, increasing to 26% in trials with 500 patients and
      38% in trials with 250 patients. In lung cancer trials, the same prediction
      required differences in response of 18% for 750 patients, 21% for 500 patients,
      and 30% for 250 patients. For time to progression for both cancer types, the
      incremental gain needed to predict a survival improvement was a median of 1.8
      months for trials with 750 patients, 2.2 months for 500 patients, and 3.3 months
      for 250 patients. INTERPRETATION: Irrespective of trial size, large differences
      in tumour response rate are needed to predict a significant survival benefit. If
      surrogates are chosen as the primary endpoint in a clinical trial, time to
      progression is the preferred measure because more modest and achievable
      differences are needed for a significant survival benefit. Trials in metastatic
      lung cancer and colorectal cancer should measure survival as their primary
      outcome unless the surrogate outcome difference is anticipated to exceed the
      threshold effect size.

PMID- 16945771
TI  - Heterogeneity of ductal carcinoma in situ and its effects on management.
AB  - Data derived from histopathological analysis, natural history, radiological
      characteristics, molecular markers, and clinical outcome indicate that ductal
      carcinoma in situ (DCIS) is a heterogeneous disease, meaning that no one
      treatment strategy is best, but rather that treatment should be personalised and
      entail a systematic and rigorous multidisciplinary approach. Many women with DCIS
      will develop actual invasive carcinoma over time, whereas others-especially those
      with low-grade cancers-will not. At the moment, identification of patients at low
      risk of recurrence risk is very difficult (that is, such people for whom further
      treatment beyond lumpectomy is not needed). In this context, molecular profiling
      analysis is a promising method to guide management decisions. In this Review,
      various treatment strategies for DCIS will be reviewed, highlighting the
      limitations of randomised trials. Furthermore, discussions about the role of
      sentinel-node biopsy and tamoxifen in disease management; locoregional
      recurrence; and special clinical scenarios such as recurrent disease, DCIS after
      thoracic radiotherapy, ductal carcinoma with concurrent lobular carcinoma in
      situ, and DCIS in elderly people and in men will be presented.

PMID- 16945772
TI  - Use of selenium in chemoprevention of bladder cancer.
AB  - The anticarcinogenic potential of selenium was first identified nearly 40 years
      ago in geographical studies that reported lower death rates for cancer in regions
      with high levels of selenium. Cancer of the bladder was one of the body sites
      found to share this inverse association. Although many subsequent studies have
      been done on selenium and cancer, only a few have specifically assessed the
      relation with bladder cancer. However, the high recurrence rate and ability to
      monitor bladder urothelial-cell carcinoma make selenium a good candidate for
      chemoprevention. Evidence suggests that selenium is a biologically plausible,
      safe, and efficacious potential chemoprevention agent for bladder cancer. Large
      tertiary chemoprevention trials are needed to further investigate the role of
      selenium in the prevention of bladder cancer. Future studies should assess the
      best dose and form of selenium, and whether the protective effect of selenium
      differs between the sexes.

PMID- 16945773
TI  - Sphincter saving is the primary objective for local treatment of cancer of the
      lower rectum.

PMID- 16945774
TI  - Meningeal carcinomatosis from breast cancer treated with intrathecal trastuzumab.

PMID- 16945775
TI  - Transoesophageal endoscopic-ultrasonography-guided 125I permanent brachytherapy
      for unresectable mediastinal lymphadenopathy.

PMID- 16945776
TI  - Metastatic primary peritoneal carcinoma presenting as tension hydrothorax.

PMID- 16945777
TI  - Therapeutic moments.

PMID- 16945778
TI  - Maternal and fetal stress responses during birth: adaptive or maladaptive?

PMID- 16945779
TI  - An exploration of negative thoughts as a normal phenomenon after childbirth.
AB  - The period following the birth of a child brings many transitions into a woman's
      life, which can effect major psychological and social changes, including feelings
      of loss. If new mothers experience negative thoughts at this time, when societal
      expectations are of happiness, this may lead to feelings of unacceptability and
      guilt. This study aimed to investigate the prevalence of negative thoughts after
      childbirth in nondepressed mothers. Following the identification of negative
      thoughts experienced by women who had suffered postnatal depression, a
      quantitative survey was conducted, which asked nondepressed mothers to indicate
      how often they experienced the negative thoughts or images identified by
      depressed mothers. One hundred and fifty-eight returned questionnaire packs were
      included in the analyses. The 158 nondepressed mothers acknowledged experiencing
      all but one of the 54 negative cognitions. Negative cognitions usually associated
      with postnatal depression are also experienced by mothers who are not considered
      depressed. This information provides evidence for reassuring new mothers that
      negative thoughts after childbirth are common. This, in turn, may help to reduce
      feelings of guilt associated with experiencing negative thoughts in the
      postpartum period.

PMID- 16945780
TI  - What constitutes a good childbirth? A qualitative study of pregnant Finnish
      women.
AB  - The aim of this study was to describe pregnant Finnish women's perceptions of a
      good childbirth. Data were collected through semistructured interviews in
      maternity health care clinics and maternity hospitals. Data interpretation was
      based on content analysis. A purposive sample of 24 pregnant women aged 19 to 45,
      half of them expecting their first child, were interviewed. Five main issues were
      seen by informants as important in the course of childbirth: 1) unhurried
      atmosphere, 2) normality, 3) reasonable duration of labor, 4) security, and 5)
      control. Participants did not expect much from their birth companions, although
      some mentioned various tasks for them. The three main issues considered important
      for the role of staff were the professionals'1) personal characteristics, 2)
      attitudes toward the childbearing woman, and 3) way they acted. The question
      about the physical environment was found quite irrelevant by some women, and only
      a few had special wishes related to the birthing environment. None of the
      participants voiced opposition to obstetric interventions, but some were willing
      to avoid them if possible. Informed consent for interventions was seen as very
      important. These results suggest that health care providers are challenged to
      provide individualized care for every woman.

PMID- 16945781
TI  - Attitudes, perceived ability, and knowledge about depression screening: a survey
      of certified nurse-midwives/certified midwives.
AB  - A survey of certified nurse-midwives/certified midwives (CNMs/CMs) attending the
      2004 American College of Nurse-Midwives (ACNM) annual meeting was undertaken to
      describe the depression screening practices of CNMs/CMs and to examine factors
      associated with depression screening. A relationship was found between attitude,
      perceived ability, knowledge, education level, and depression screening, with
      attitude and perceived ability having the strongest positive relationship to
      screening. Attitude, perceived ability, knowledge, and education accounted for
      20% of the variance in depression screening conducted by CNMs/CMs. These findings
      suggest that the management of depression is not fully integrated into the
      practice of many CNMs/CMs. Further research is needed to assess screening
      methods, interventions for the treatment of depression, and evaluation of
      institutional barriers to depression screening.

PMID- 16945782
TI  - Expectations, perceptions, and management of labor in nulliparas prior to
      hospitalization.
AB  - This ethnographic qualitative study was designed to explore the phenomenon of
      prehospitalization labor from the perspective of nulliparous women. Twenty-three
      women were interviewed in the early postpartum period using a semistructured
      interview guide. The participants recounted their experiences with labor onset
      recognition and management before being admitted to the hospital for birthing.
      Qualitative analyses included verbatim transcription of audiotaped interviews,
      line-by-line coding, and categorization of data into codes and categories.
      Interpretive analyses were validated with a collaborative research team and the
      participants themselves. The central theme that emerged from this study was
      confronting the relative incongruence between expectations and actual
      experiences. Supporting categories included: expectations about the labor
      experience, identifying labor onset, managing the physical and emotional
      responses to labor, supportive resources, and decision making about hospital
      admission. Early labor experiences in nulliparas offer insight into the
      contributions of both expectations and environment to adaptation in labor.
      Midwives and perinatal nurses are in a unique position to design interventions
      that support and reinforce laboring women's activities outside of the hospital
      setting.

PMID- 16945783
TI  - English midwives' views and experiences of intrapartum fetal heart rate
      monitoring in women at low obstetric risk: conflicts and compromises.
AB  - Over the last 20 years in the United Kingdom, midwives have implemented the
      routine use of intrapartum fetal monitoring regardless of the risk status of
      laboring women. This practice is at odds with the published research. The
      discrepancy between practice and best evidence merits further investigation. A
      qualitative study was conducted to evaluate midwives' attitudes and experiences
      about the use of fetal monitoring for women at low obstetric risk. Fifty-eight
      midwives working in two hospitals in the north of England were interviewed by
      using a semistructured approach. The taped interviews were transcribed and
      analyzed by using a general thematic approach. Issues included midwives'
      perceptions of low-risk status, the socialization of midwives, and the loss of
      woman-centered care. Midwives subscribed to the notion of woman-centered care,
      but because of a complexity of factors experienced in their daily working lives,
      they felt vulnerable when attempting to implement evidence-based fetal monitoring
      practices. Midwives regretted the loss of a woman-centered approach to care when
      technologic methods of intrapartum fetal heart rate monitoring were used
      indiscriminately. An appreciation of the complex factors affecting the ability of
      midwives to implement evidence-based practice is important when attempting to
      facilitate the development of appropriate fetal monitoring practices for women at
      low obstetric risk.

PMID- 16945784
TI  - Abuse disclosure in privately and medicaid-funded pregnant women.
AB  - Disclosure of abuse by pregnant women can vary depending on whether the woman is
      assessed directly by a trained interviewer versus written questionnaires, and if
      she is asked repeatedly during the course of pregnancy. One thousand pregnant
      women were enrolled in a randomized clinical trial designed to assess the effects
      of a nursing case management intervention on the mental and physical well-being
      of pregnant women experiencing or at risk for abuse. Thirteen percent of the
      total study participants reported current abuse and/or abuse within the past
      year, with only 2% of those reporting that the abuse occurred during pregnancy.
      The incidence of reported abuse was much higher among Medicaid-funded women
      (28.9%) than privately insured women (8.7%). Regardless of source of payment,
      women reporting abuse were significantly younger, less educated, nonwhite with
      lower income, and had significantly higher stress and lower self-esteem than
      women not reporting abuse. A high incidence of women reporting intimate partner
      violence described being choked on the Danger Assessment Screen (34%). We
      strongly urge that choking be added to routine screening questions used during
      pregnancy and that the Danger Assessment tool is used for further evaluation of
      women who screen positive. In addition, we believe another barrier to reporting
      abuse was fear of being reported to child protective services, contributing to
      the overall low rate of abuse disclosure.

PMID- 16945785
TI  - Experience of Taiwanese women living with nausea and vomiting during pregnancy.
AB  - Two common symptoms of pregnancy are nausea and vomiting, which, for some women,
      cause great discomfort and profoundly impact daily life. A descriptive
      phenomenological method was used to understand how Taiwanese women deal with
      nausea and vomiting during pregnancy. A purposive sample of 10 expectant mothers
      participated in the study. A transcription of each informant's verbal description
      of her nausea and vomiting experience was made and analyzed using Colaizzi's
      phenomenological methodology. Four themes emerged from the interview data after
      inductively analyzing the narrative content concerning nausea and vomiting: 1)
      understanding nausea and vomiting, 2) finding coping strategies, 3) psychosocial
      adaptation, and 4) needing support. The results also indicated the importance of
      social support to pregnant women's health, including instrumental and emotional
      forms of support. Health professionals, however, were not mentioned in the
      mothers' narratives as a source of support. The issues of social support,
      language translation, and western and eastern perspectives on nausea and vomiting
      and cultural differences in perceptions of their severity are discussed.

PMID- 16945786
TI  - Blue hours.

PMID- 16945788
TI  - Atrial activation during atrioventricular nodal reentrant tachycardia: studies on
      retrograde fast pathway conduction.
AB  - BACKGROUND: Detailed right and left septal mapping of retrograde atrial
      activation during typical atrioventricular nodal reentrant tachycardia (AVNRT)
      has not been undertaken and may provide insight into the complex physiology of
      AVNRT, especially the anatomic localization of the fast and slow pathways.
      OBJECTIVES: The purpose of this study was to investigate the pattern of
      retrograde atrial activation during typical AVNRT by means of right-sided and
      left-sided septal mapping and implementation of pacing maneuvers for separating
      atrial and ventricular electrograms recorded during tachycardia. METHODS: Twenty
      two patients with slow-fast AVNRT were studied by means of simultaneous His
      bundle recordings from the right and left sides of the septum. Patterns of
      retrograde atrial activation were recorded during tachycardia following specific
      pacing maneuvers and during right ventricular apical (RVA) pacing at the
      tachycardia cycle length. RESULTS: The pattern of retrograde atrial activation
      could be mapped in 17 of 22 patients during AVNRT. In 9 (53%) patients, the
      earliest retrograde atrial activation was recorded on the left side of the
      septum, in 3 (17%) patients on the right side, and in 5 (29%) patients both right
      and left atrial septal electrograms occurred simultaneously. Stimulus to atrial
      electrogram times recorded during RVA pacing in 14 patients were 138.5 ms from
      the right His bundle, 134.5 ms from the left His bundle, and 148.0 ms from the
      ostium of the coronary sinus (P <.001). The predominant site of earliest
      retrograde atrial activation during RVA pacing was the left side of the septum
      (10 patients [71%]). Only 8 (57%) of 14 patients demonstrated concordance in the
      pattern of retrograde atrial activation during AVNRT and RVA pacing. CONCLUSION:
      Earliest retrograde atrial activation during AVNRT is most often recorded on the
      left side of the septum. Breakthrough of atrial activation may be discordant from
      that observed during RVA pacing.

PMID- 16945789
TI  - Unraveling the mysteries of the AV node.

PMID- 16945791
TI  - Choosing tools for QT correction.

PMID- 16945790
TI  - Bazett and Fridericia QT correction formulas interfere with measurement of drug
      induced changes in QT interval.
AB  - BACKGROUND: The QT interval on the ECG is prolonged by more than 50 marketed
      drugs, an effect that has been associated with syncope and/or sudden cardiac
      death due to an arrhythmia. Because changes in heart rate also change the QT
      interval, it has become standard practice to use a correction formula, such as
      the Bazett formula, to normalize the QT interval to a heart rate of 60 bpm, that
      is, the rate-corrected QT or QTc. Numerous other formulas have been devised to
      make this correction, including the Fridericia, Hodges, and Framingham formulas.
      OBJECTIVES: The purpose of this study was to investigate how the Bazett formula
      and three other formulas influence assessment of the QT-prolonging effect of the
      potassium channel-blocking drug ibutilide. METHODS: Using a standardized physical
      activity protocol, the QT interval was assessed over a broad range of heart rates
      before and after an infusion of ibutilide (4.75 microg/kg) that produced a stable
      15- to 20-ms QT prolongation in consenting normal subjects (9 men and 9 women).
      The QT interval was measured digitally over a range of heart rates from 60 to 120
      bpm, and then four correction formulas (Bazett, Fridericia, Framingham, or
      Hodges) were applied. The uncorrected change in QT interval due to ibutilide was
      compared with the change using each of the formulas by repeated measures analysis
      of variance. RESULTS: At heart rates from 60 to 120 bpm, the Bazett and
      Fridericia correction formulas overestimated the change in QT in both men and
      women (P <.001). However, the Framingham and Hodges formulas did not alter the
      accuracy of the assessment of QT interval change. CONCLUSION: Rate correction of
      QT intervals using the standard Bazett and Fridericia formulas can introduce
      significant errors in the assessment of drug effects on the QT interval. This has
      implications for the clinical assessment of drug effects and for the safety
      assessment of new drugs under development.

PMID- 16945792
TI  - Elevated defibrillation thresholds in patients undergoing biventricular
      defibrillator implantation: incidence and predictors.
AB  - BACKGROUND: The biventricular implantable cardioverter-defibrillator (ICD) is an
      important therapy for select patients with severe heart failure. Given reported
      risk factors for elevated defibrillation thresholds (DFTs), patients undergoing
      biventricular ICD placement would be suspected of having a higher incidence of
      elevated DFT. OBJECTIVES: The purpose of this study was to examine the clinical
      predictors and mortality risk of elevated DFTs in patients receiving a
      biventricular ICD. METHODS: Characteristics of patients undergoing biventricular
      ICD placement with an elevated DFT were compared to those without an elevated
      DFT. RESULTS: An elevated DFT was found in 14 (12%) of 121 patients. Mean QRS
      duration was 210 +/- 50 ms in the elevated DFT group and 171 +/- 36 ms in the
      normal DFT group (P = .01). Patients with a QRS duration >or=200 ms were more
      likely to have an elevated DFT than those with a duration <200 ms (odds ratio
      13.4, 95% confidence interval 3.1-66.7, P <.01). No other clinical
      characteristics were associated with an elevated DFT. More than 90% of patients
      with an elevated DFT achieved an adequate safety margin through system
      modification or manipulation of their drug regimen. An elevated DFT did not have
      an impact on 2-year mortality. CONCLUSION: Patients with a biventricular ICD had
      a 12% incidence of elevated DFT in our sequential patient cohort. QRS duration
      prior to biventricular ICD placement is the most powerful predictor of patients
      at risk for an elevated DFT. An elevated DFT does not have an impact on
      mortality, perhaps because of successful implementation of system modifications
      to ensure an adequate defibrillation safety margin.

PMID- 16945793
TI  - Predicting elevated defibrillation energy requirements in heart failure with
      reasonable probability.

PMID- 16945794
TI  - Left superior vena cava isolation in patients undergoing pulmonary vein antrum
      isolation: impact on atrial fibrillation recurrence.
AB  - BACKGROUND: A persistent left superior vena cava (SVC) can be an arrhythmogenic
      source in patients with atrial fibrillation (AF) through connections from the
      coronary sinus (CS) and the left atrium (LA). The left SVC can be electrically
      isolated. However, little clinical data about the impact of left SVC
      disconnection on AF outcome are available. We report on six patients with left
      SVC and recurrent AF. OBJECTIVES: The purpose of this study was to assess the
      impact of left SVC isolation on AF recurrence. METHODS: Six patients (4 men and 2
      women; age 50 +/- 6.4 years) with symptomatic drug-refractory AF and persistent
      left SVC presented to our laboratory for treatment. Four of the patients had left
      SVC isolation only because there was no conduction recovery in the pulmonary
      veins (PVs) after several previous procedures. RESULTS: Conduction between the
      left SVC and the CS and LA was documented, as was spontaneous ectopies in three
      patients that degenerated into AF in one patient. Isolation of the left SVC was
      successful in all patients. Isolation was relatively easy to perform (10.25 +/-
      1.6 minutes), with no complications. After follow-up of 13 +/- 7.4 months, all
      patients were in sinus rhythm and free from AF without antiarrhythmic drugs.
      CONCLUSION: This study stresses the importance of looking for unusual sources of
      AF in patients presenting for repeat procedures or in those in whom the PVs have
      been ruled out as a source triggering AF. We present clinical evidence that in
      patients with AF and left SVC, isolation of the PVs only may not be sufficient to
      suppress AF. Thus, diagnosis and isolation of the left SVC appears critical to
      preventing AF recurrence in patients with AF when ablation is considered.

PMID- 16945795
TI  - Clinical predictors and outcomes associated with acute return of pulmonary vein
      conduction during pulmonary vein isolation for treatment of atrial fibrillation.
AB  - BACKGROUND: Pulmonary vein electrical isolation (PVI) is an effective treatment
      for atrial fibrillation (AF). However, recurrence of pulmonary vein (PV)
      conduction after ablation may limit long-term success. OBJECTIVE: We sought to
      determine the clinical predictors of acute PV reconnection during PVI and assess
      the long-term clinical outcomes associated with this phenomenon. METHODS: We
      studied all patients with AF referred for PVI between November 2000 and August
      2004. Over the course of the study period, PVI of arrhythmogenic PVs was
      performed segmentally using a 4-mm tip (52 degrees , 40 W, up to 90 seconds) or 8
      mm tip catheter (50 degrees , 70 W, up to 60 seconds). PVI was defined as entry
      and exit block using a multipolar Lasso catheter. All veins were resampled to
      confirm isolation after 20-60 minutes. AF control was defined as no AF on or off
      a previously ineffective antiarrhythmic drug. Follow-up data included
      transtelephonic monitoring and clinical data collection from patient interviews.
      RESULTS: There were 424 patients who underwent isolation of 1,347 PVs during the
      study period. Acute reconnection of at least one PV occurred in 211 (50%) of the
      424 patients and 326 (24%) of 1,347 of the PVs targeted. The left superior PV was
      most likely to acutely recover conduction compared with the other veins (left
      superior 31%, right superior 26%, right inferior 22%, left inferior 24%; P =
      .03). Patients with acute reconnection were more likely to be older, have a
      larger left atrium, have a history of hypertension or obstructive sleep apnea,
      and demonstrate persistent AF. After a single procedure, AF control was achieved
      in 153 (70%) of the 213 patients who demonstrated acute PV reconnection compared
      with 148 (73%) of 211 patients without acute PV reconnection observed (P = .52).
      CONCLUSIONS: Acute return of PV conduction is common after successful PVI and is
      more likely to occur in older patients with nonparoxysmal AF, hypertension, a
      large left atrium, and sleep apnea. There was no significant difference in acute
      PV reconnection between the 4-mm and 8-mm tip RF catheter despite differences in
      power and duration of energy delivery. Furthermore, there was no effect of PV
      reconnection on long-term AF control after repeated disconnection was performed.

PMID- 16945796
TI  - Is pulmonary vein isolation by segmental ostial ablation a correct approach for
      treatment of atrial fibrillation?

PMID- 16945797
TI  - Characterization of an LQT5-related mutation in KCNE1, Y81C: implications for a
      role of KCNE1 cytoplasmic domain in IKs channel function.
AB  - BACKGROUND: Y81C is a new long QT-5 (LQT5)-related KCNE1 mutation, which is
      located in the post-transmembrane domain (post-TMD) region in close proximity to
      three other LQT5 mutations (S74L, D76N, and W87R). OBJECTIVE: We examine the
      effects of Y81C on the function and drug sensitivity of the slow delayed
      rectifier channel (I(Ks)) formed by KCNE1 with pore-forming KCNQ1 subunits. We
      also infer a structural basis for the detrimental effects of Y81C on I(Ks)
      function. METHODS: Wild-type (WT) and mutant (harboring Y81C) I(Ks) channels are
      expressed in oocytes or COS-7 cells. Channel function and KCNQ1 protein
      expression/subcellular distribution are studied by techniques of
      electrophysiology, biochemistry, and immunocytochemistry. Ab initio structure
      predictions of KCNE1 cytoplasmic domain are performed by the Robetta server.
      RESULTS: Relative to WT KCNE1, Y81C reduces I(Ks) current amplitude and shifts
      the voltage range of activation to a more positive range. Y81C does not reduce
      whole-cell KCNQ1 protein level or interfere with KCNQ1 trafficking to cell
      surface. Thus, its effects are mediated by altered KCNQ1/KCNE1 interactions in
      cell surface channels. Importantly, Y81C potentiates the effects of an I(Ks)
      activator. Preserving the aromatic or hydroxyl side chain at position 81 (Y81F or
      Y81T) does not prevent the detrimental effects of Y81C. Structure predictions
      suggest that the post-TMD region of KCNE1 may adopt a helical secondary
      structure. CONCLUSION: We propose that the post-TMD region of KCNE1 interacts
      with the KCNQ1 channel to modulate I(Ks) current amplitude and gating kinetics.
      Other LQT5 mutations in this region share the Y81C phenotype and probably affect
      the I(Ks) channel function by a similar mechanism.

PMID- 16945798
TI  - Mutations in KCNE1 in long QT syndrome (LQTS): insights into mechanism of LQTS
      and drug sensitivity?

PMID- 16945799
TI  - Monophasic action potentials and activation recovery intervals as measures of
      ventricular action potential duration: experimental evidence to resolve some
      controversies.
AB  - BACKGROUND: Activation recovery intervals (ARIs) and monophasic action potential
      (MAP) duration are used as measures of action potential duration in beating
      hearts. However, controversies exist concerning the correct way to record MAPs or
      calculate ARIs. We have addressed these issues experimentally. OBJECTIVES: To
      experimentally address the controversies concerning the correct way to record
      MAPs or calculate ARIs. METHODS: Left ventricular local electrograms were
      recorded in isolated pig hearts with an exploring electrode grid, with a KCl
      reference electrode on the left ventricular myocardium, the aortic root, or the
      left atrium. Local activation was determined from calculated Laplacian
      electrograms. RESULTS: With the KCl electrode on the aortic root, local
      electrograms represented local activation. However, with the KCl electrode on the
      myocardium remote from the exploring electrode, a combined electrogram emerged
      consisting of local activation recorded from the grid and remote activation
      recorded from the reference electrode. The remote, inverted monophasic component
      did not show propagation and did not correlate with the Laplacian complex. When
      the KCl electrode was placed on the atrium during AV block, remote atrial
      monophasic components were completely dissociated from local, ventricular
      deflections. At left ventricular sites with a positive T wave, the Laplacian
      signal showed that the end of the T wave was caused by remote repolarization.
      During cooling-induced regional action potential prolongation, the T wave became
      negative, whereby the positive flank of the T wave remained correlated with
      repolarization (recorded with a MAP at the same site). CONCLUSIONS: MAPs are
      recorded from the depolarizing electrode. In both negative and positive T waves,
      the moment of maximum dV/dt corresponds to local repolarization.

PMID- 16945800
TI  - Controversies in measuring repolarization using extracellular recordings: why
      should we care?

PMID- 16945801
TI  - A comparison of the output characteristics of several implantable cardioverter
      defibrillators.
AB  - BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are effective for
      primary and secondary prevention of sudden cardiac death due to ventricular
      arrhythmias. However, despite wide clinical use, there are no generally accepted
      standardized protocols to characterize and report the output capabilities of
      ICDs. OBJECTIVE: The objective of this study was to measure and compare the
      output characteristics of standard-output and high-output ICDs from several
      manufacturers under a common set of conditions. METHODS: The output
      characteristics of ICDs randomly selected from hospital stock were measured. The
      energy delivered for each shock to a range of fixed loads (25-75 Omega) was
      computed from the voltage waveform and the corresponding load. RESULTS: Delivered
      energy varied by approximately 4 J over the range of loads tested and varied
      between devices (high-output 33.8-35 J; standard-output 26.7-28.6 J, at 50
      Omega). Leading-edge voltage varied by approximately 6% over the range of loads
      tested and varied between devices (high-output 738-792 V; standard-output 593-797
      V, at 50 Omega). Pulse width varied by a factor of approximately 3 over the range
      of loads tested and varied between devices (high-output 10-14.5 ms; standard
      output 9-12.2 ms, at 50 Omega). Observed variations between devices and with load
      were significant (P <.001). CONCLUSIONS: Potentially important differences in
      output characteristics of different ICD systems exist and merit further clinical
      investigation. The reporting of ICD output characteristics should be
      standardized. Additionally, it is recommended that manufacturers report output
      characteristics as a function of load over the typical range of patient loads
      clinically encountered.

PMID- 16945802
TI  - ICD waveforms: what really matters?

PMID- 16945803
TI  - Role of intramural virtual electrodes in shock-induced activation of left
      ventricle: optical measurements from the intact epicardial surface.
AB  - BACKGROUND: According to one hypothesized mechanism of defibrillation, shocks
      directly excite the bulk of ventricular myocardium in the excitable state due to
      intramural virtual electrodes; however, this hypothesis has not been examined in
      intact myocardium. OBJECTIVES: The purpose of this study was examine the role of
      intramural virtual electrodes in shock-induced activation of intact left
      ventricular (LV) tissue. METHODS: Twelve isolated porcine LV preparations were
      stained with a transmembrane potential (V(m))-sensitive dye by two methods: (1)
      surface staining and (2) global staining via coronary perfusion. Shocks (E
      approximately 0.8-48 V/cm, duration = 10 ms) were applied across the wall from
      epicardium to endocardium during diastole via transparent electrodes. Shock
      induced V(m) responses were measured optically from the intact epicardial surface
      after surface staining and global staining. RESULTS: Surface-staining recordings
      demonstrated different V(m) responses to cathodal and anodal shocks. Whereas
      cathodal shocks caused depolarization and rapid activation of the epicardial
      surface, anodal shocks induced hyperpolarization and delayed surface activation.
      In contrast, global-staining V(m) responses to cathodal and anodal shocks were
      qualitatively similar. Both responses were characterized by activation with small
      latency and rapid propagation. Weak shocks of both polarities induced monotonic
      action potential upstrokes; stronger shocks induced nonmonotonic upstrokes with
      two rising phases at shock onset and end. Such features of global-staining V(m)
      responses as make activation of the epicardium by anodal shocks and the
      nonmonotonic action potential upstrokes can be explained by the presence of
      subepicardial intramural virtual electrodes. CONCLUSION: These data suggest that
      shocks induce intramural virtual electrodes that directly excite LV tissue and
      account for the shape of optical V(m) responses recorded from the epicardial
      surface.

PMID- 16945804
TI  - Genetic and biophysical basis for bupivacaine-induced ST segment elevation and
      VT/VF. Anesthesia unmasked Brugada syndrome.
AB  - BACKGROUND: Brugada syndrome is an inherited disease associated with sudden
      cardiac death. The electrocardiographic pattern associated with Brugada syndrome
      has been linked to the use of sodium channel blockers, including antiarrhythmics,
      trycyclics and anesthetics. OBJECTIVE: We report a case of bupivacaine-induced
      Brugada syndrome, in which we investigated the genetic, biophysical and path
      physiological mechanism involved. METHODS AND RESULTS: The patient developed a
      Brugada-like electrocardiographic pattern twice under the influence of
      bupivacaine. The first occurrence was accompanied by ventricular tachycardia (VT)
      which subsided after withdrawal of the anesthetic. The VT was also observed
      during co-administration of diltiazem and isosorbide-5-mononitrate, agents
      thought to facilitate ST segment elevation in the Brugada syndrome. Genetic
      analysis revealed a missense mutation in the alpha subunit of the cardiac sodium
      channel, SCN5A. Biophysical analysis by whole-cell patch-clamping revealed a
      reduction in sodium current as a result of the mutation. The study of bupivacaine
      in the wedge model revealed use-dependent changes in conduction, heterogeneous
      loss of the action potential dome in RV epicardium and phase 2 re-entry when the
      preparations were pretreated with low concentrations of the calcium channel
      blocker verapamil. CONCLUSION: Our findings indicate that bupivacaine may induce
      the electrocardiographic and arrhythmic manifestations of the Brugada syndrome in
      silent carriers of SCN5A mutations. The data have important implications in the
      management of patients who develop ST segment elevation when under the influence
      of anesthetics such as bupivacaine.

PMID- 16945805
TI  - Brugada syndrome and the use of anesthetics.

PMID- 16945806
TI  - Characterization of J wave in a patient with idiopathic ventricular fibrillation.

PMID- 16945807
TI  - Atypical atrioventricular nodal reentrant tachycardia in a patient with
      fasciculoventricular pathway.

PMID- 16945808
TI  - Focal atrial fibrillation originating from the coronary sinus musculature.

PMID- 16945809
TI  - Elucidation of the spatial ventricular gradient and its link with dispersion of
      repolarization.
AB  - The ventricular gradient, a notion conceived by Wilson et al during the 1930s,
      has contributed considerably to a better understanding of the ECG manifestations
      of the cardiac repolarization process. The power of the ventricular gradient is
      its ability to assess the primary factors that contribute to the T wave (i.e.,
      heterogeneity of action potential morphology throughout the ventricles) in the
      presence of secondary factors contributing to the T wave (i.e., heterogeneity in
      ventricular depolarization instants). Where T-wave morphology is an ECG
      expression of heterogeneity of the repolarization, the ventricular gradient
      discriminates between primary or secondary causes of such heterogeneity. Besides
      the spatial ventricular gradient (Burger's three-dimensional elaboration of
      Wilson's two-dimensional concept), body surface mapping of local components of
      the ventricular gradient has emerged as a technique for assessing local
      ventricular action potential duration heterogeneity. The latter is believed to
      contribute to localization of arrhythmogenic areas in the heart. The spatial
      ventricular gradient, which can be computed on the basis of a regular routine ECG
      and does not require body surface mapping, aims to assess the overall
      heterogeneity of ventricular action potential morphology. This review addresses
      the nature and diagnostic potential of the spatial ventricular gradient. The main
      focus is the role of the spatial ventricular gradient in ECG assessment of
      dispersion of repolarization, a key factor in arrhythmogeneity.

PMID- 16945810
TI  - Virtual electrode hypothesis of defibrillation.

PMID- 16945811
TI  - A nonsustained tachycardia: What is the mechanism?

PMID- 16945812
TI  - How to perform encircling ablation of the left atrium.

PMID- 16945813
TI  - Transthoracic epicardial catheter ablation of ventricular tachycardia.

PMID- 16945814
TI  - An excellent refinement of the postpacing interval--tachycardia cycle length (PPI
      TCL) and stimulus-atrial--ventriculoatrial (SA-VA) criteria.

PMID- 16945815
TI  - Benefit of millisecond waveform duration for patients with high defibrillation
      thresholds.

PMID- 16945819
TI  - Bivalirudin versus unfractionated heparin in patients undergoing percutaneous
      coronary intervention after acute myocardial infarction.
AB  - BACKGROUND: Bivalirudin is replacing heparin as the anticoagulant agent of choice
      for elective percutaneous coronary intervention (PCI). This study aimed to assess
      the safety and clinical outcomes of bivalirudin versus unfractionated heparin
      (UFH) in patients undergoing PCI for acute myocardial infarction (AMI). METHODS:
      A cohort of 672 consecutive patients presenting with AMI without prior
      thrombolytic therapy were treated with either bivalirudin (216 patients) or UFH
      (456 patients). Platelet glycoprotein IIb/IIIa inhibitors were administered at
      the operator's discretion. The in-hospital, 30-day, and 6-month outcomes of the
      two groups were compared. RESULTS: Baseline clinical and angiographic
      characteristics were similar between the groups. In-hospital complications were
      similar, although there was a trend of a less major hematocrit drop in the
      bivalirudin group (0.9% vs. 3.1%, P=.09). All clinical outcomes were similar
      between the groups at 30-day and 6-month follow-ups. There was no statistical
      significance for acute thrombosis and subacute thrombosis between the groups, and
      there was no late thrombosis from either group. The event-free survival rate was
      similar between the groups (P=.41). CONCLUSION: The use of bivalirudin in
      patients undergoing PCI after AMI is safe and feasible. Bivalirudin should be
      considered as an alternative anticoagulant agent during PCI to treat patients
      presenting with AMI.

PMID- 16945820
TI  - Safety of intramyocardial injection of autologous bone marrow cells to treat
      myocardial ischemia in pigs.
AB  - OBJECTIVE: The purpose of this study is to determine the potential adverse
      consequences of intracardiac injections of bone marrow mononuclear cells (BMCs)
      to facilitate the revascularization of ischemic myocardium. BACKGROUND: Bone
      marrow mononuclear cells are used to treat heart failure, though there are few
      studies that evaluated the safety of BMC transplantation for chronic myocardial
      ischemia. METHODS: The pigs received coronary ameroid constrictors to induce
      chronic myocardial ischemia and left ventricular dysfunction. At 4 weeks,
      autologous BMCs were injected intramyocardially by Boston Scientific Stiletto
      catheter with low-dose (10(7) cells) or high-dose BMC (10(8)). Control animals
      received saline. Blood samples were collected for hematological and chemical
      indices, including cardiac enzyme levels at regular time intervals
      postinfarction. At 7 weeks, animals underwent electrophysiological study to
      evaluate the arrhythmic potential of transplanted BMC, followed by necropsy and
      histopathology. RESULTS: No mortalities were associated with intramyocardial
      delivery of BMC or saline. At Day 0, the total creatine phosphokinase (CPK) was
      in the normal range in all groups. All groups had significant elevations in CPK
      after ameroid placement, with no significant differences between groups. At 7
      weeks, CPK in all groups had returned to pretreatment levels.
      Electrophysiological assessment revealed that one control animal had an inducible
      arrhythmia. No arrhythmias were induced in low- or high-dose BMC-treated pigs.
      There were no histopathological changes associated with BMC injection.
      CONCLUSION: This study showed, in a clinically relevant large-animal model, that
      catheter-based intramyocardial injection of autologous BMC into ischemic
      myocardium is safe.

PMID- 16945821
TI  - Hyperbaric oxygen: a new drug in myocardial revascularization and protection?
AB  - Ischemia-reperfusion injury (IRI) occurs following coronary artery
      revascularization. Reactive oxygen species (ROS) were initially thought to play a
      role in the pathogenesis of this injury. However, the evidence for this is
      inconclusive. Recent studies involving ischemic preconditioning have identified
      ROS as potential mediators for the cardioprotective effects observed following
      this technique. Furthermore, cardiac studies involving IRI and the use of
      hyperbaric oxygen (HBO) have demonstrated the ability of HBO to induce
      cardioprotection and to attenuate IRI. This review suggests the possible role for
      HBO as a new drug in the arena of myocardial revascularization and cellular
      protection. While there is mounting clinical evidence for this, a methodological
      understanding of HBO's cellular mechanisms of actions appears to be lacking. As
      such, this article attempts to draw the similarity between HBO and other
      protective oxidative stress mechanisms and then to speculate in an evidence-based
      manner its possible cellular mechanistic role as a drug via the generation of
      ROS.

PMID- 16945822
TI  - Double jeopardy: balance between bleeding and stent thrombosis with prolonged
      dual antiplatelet therapy after drug-eluting stent implantation.
AB  - Prolonged dual antiplatelet therapy with aspirin and clopidogrel is mandatory
      after drug-eluting stent (DES) implantation because of potential increase risk of
      stent thrombosis compared to bare-metal stents. As more DES are being implanted,
      many of these patients will undergo non-cardiac surgery whilst on antiplatelet
      therapy. The optimal management of perioperative antiplatelet therapy is not well
      established. The risk of excessive bleeding associated with antiplatelet therapy
      needs to be balanced against the risk of stent thrombosis with interruption of
      antiplatelet therapy on a case-to-case basis.

PMID- 16945823
TI  - Is sirolimus better than paclitaxel? A review of the comparative data on drug
      eluting stents.
AB  - Drug-eluting stents have been unequivocally demonstrated to reduce in-stent
      restenosis when compared to bare metal stents, with resultant lower rates of
      repeat revascularization. Comparative data are now emerging which compare the
      performance of sirolimus- and paclitaxel-eluting stents to each other rather than
      to bare metal stents. In this article, we review these data with the aim of
      placing the studies in context thereby providing an overall view of this rapidly
      developing field as it stands at present.

PMID- 16945824
TI  - A concise review of DNA damage checkpoints and repair in mammalian cells.
AB  - DNA of eukaryotic cells, including vascular cells, is under the constant attack
      of chemicals, free radicals, or ionizing radiation that can be caused by
      environmental exposure, by-products of intracellular metabolism, or medical
      therapy. Damage may be either limited to altered DNA bases and abasic sites or
      extensive like double-strand breaks (DSBs). Nuclear proteins sense this damage
      and initiate the attachment of protein complexes at the site of the lesion.
      Subsequently, signal transducers, mediators, and finally, effector proteins
      phosphorylate targets (e.g., p53) that eventually results in cell cycle arrest at
      the G1/S, intra-S, or G2/M checkpoint until the lesion undergoes repair.
      Defective cell cycle arrest at the respective checkpoints is associated with
      genome instability and oncogenesis. When cell cycle arrest is accomplished, the
      DNA repair machinery can become effective. Important pathways in mammalian cells
      are the following: base excision repair, nucleotide excision repair, mismatch
      repair, and DSB repair. When repair is successful, the cell cycle arrest may be
      lifted. If repair is unsuccessful (e.g., by high doses of DNA-damaging agents or
      genetic defects in the DNA repair machinery), then this may lead to permanent
      cell cycle arrest (cellular senescence), apoptosis, or oncogenesis.

PMID- 16945825
TI  - Efficient transduction and seeding of human endothelial cells onto metallic
      stents using bicistronic pseudo-typed retroviral vectors encoding vascular
      endothelial growth factor.
AB  - BACKGROUND: Stents seeded with genetically modified endothelial cells (EC) may
      provide an attractive therapeutic modality for treating vascular diseases by
      combining the mechanical properties of the metallic stent with the biologic
      activity of native or genetically engineered ECs. The clinical feasibility of
      implanting seeded stents depends on the ability to achieve adequate stent
      coverage within a clinically applicable time frame. We tested the hypothesis that
      this goal could be achieved by seeding stents with human ECs overexpressing
      vascular endothelial growth factor (VEGF) and by using an efficient gene transfer
      system. METHODS AND RESULTS: Efficiency of gene transfer to human ECs using an
      amphotropic retroviral vector and a gibbon ape leukemia virus (GALV) pseudo-typed
      retroviral vector was examined and compared. For assessment of transduction
      rates, LacZ-encoding vectors were used and beta-galactosidase activity was
      determined 48 h after gene transfer. The transduction rate of primary human ECs
      using the amphotropic retroviral vector encoding the LacZ gene was low (2.9+/-2%
      of cells). Under the same conditions, the GALV pseudo-typed vector encoding LacZ
      transduced 94+/-2% of cells (P<.001). To test the effect of VEGF gene transfer on
      stent coverage, we transduced ECs using a bicistronic GALV pseudo-typed
      retroviral vector encoding either GFP alone or both VEGF and GFP. Since all
      transduced cells expressed GFP, stent coverage by ECs could be assessed by
      fluorescent inverted microscopy, which demonstrated that stent coverage by ECs
      overexpressing VEGF was more rapid and effective than coverage by ECs
      overexpressing GFP. Progressively increasing quantities of VEGF protein were
      detected in the conditioned medium of stents seeded with endothelia cells
      expressing VEGF 2, 3, and 5 days after seeding. CONCLUSIONS: High-rate gene
      transfer to human primary ECs was observed 48 h after transduction with GALV
      pseudo-typed retroviral vectors, eliminating the need for the time-consuming
      process of cell selection. Seeding with ECs overexpressing VEGF improved stent
      coverage and was associated with continuing secretion of the protein. The
      findings provide support for the feasibility of implanting genetically engineered
      biologically active cellular-coated stents.

PMID- 16945826
TI  - Optimal dosing and duration of oral everolimus to inhibit in-stent neointimal
      growth in rabbit iliac arteries.
AB  - BACKGROUND: Everolimus is an orally active derivative of sirolimus. Oral
      administration of rapamycin is efficacious in the reduction of neointima
      formation and clinical restenosis; however, its optimal dose and duration have
      not been determined. METHODS: New Zealand White rabbits were divided into three
      groups. The first (low-dose) group received 1.5 mg/kg everolimus 1 day before
      stenting, followed by 0.75 mg/kg/day everolimus for 28 days. The second (high
      dose) group received 6 mg/kg everolimus 1 day before, on the day of, and on the
      day after stenting, followed by 2 mg/kg/day for 4 days. The third (placebo) group
      received a matching volume of vehicle similar to that of Group 2. Twenty-eight
      days after stenting, animals were euthanized and morphometry was performed.
      RESULTS: In the high-dose group, circulating everolimus levels corresponded with
      administrated dose levels; by Day 12, no circulating everolimus could be
      detected. In the low-dose everolimus group, levels remained constant up to 28
      days. When compared with placebo, low-dose everolimus was associated with a
      significant reduction in medial thickness (32%), neointimal area (60%), and
      percent stent stenosis (33%); however, high-dose everolimus had no significant
      effect. CONCLUSIONS: In conclusion, oral everolimus suppresses in-stent
      neointimal growth in rabbit iliac arteries. Four weeks of low-dose everolimus is
      more effective than 7 days of high-dose everolimus.

PMID- 16945827
TI  - Cutting balloon inflation for drug-eluting stent underexpansion due to
      unrecognized coronary arterial calcification.
AB  - Unrecognized calcification is a cause of stent underexpansion which significantly
      increases the subsequent risks of restenosis and/or stent thrombosis. We describe
      the use of cutting balloon inflation within the implanted stent which overcame
      calcific restraint unresponsive to high pressure inflations with non-compliant
      balloons.

PMID- 16945828
TI  - Systolic cessation of the flow in the mid stent segment of the previously stented
      ostial vein graft with normal flow during diastole. A case report and brief
      review.
AB  - We present a case of intermittent cessation of blood flow through stent struts
      during systole, with normal flow during diastole in the previously stented ostial
      vein graft. After reviewing the initial procedure, we discovered that the
      operator had difficulty in positioning the stent. After stent deployment, the
      ostial stent was malpositioned and was protruding more than 50% into the aorta.
      During systole, the contrast in the stent struts, which are situated in the
      aorta, was being washed off by systolic blood flow, while in the diastole, the
      flow of contrast was normal. This is the first case report of this observation
      with a brief review.

PMID- 16945829
TI  - Closure of patent Potts shunt with aortic endoluminal stent graft.
AB  - Pulmonary hypertension secondary to residual Potts shunt is not an uncommon
      phenomenon. A 59-year-old male with a history of tetralogy of Fallot was noted,
      on a full heart study, to have persistent pulmonary hypertension, normal left
      ventricular function, severe aortic regurgitation, and a residual Potts shunt. A
      previous surgical attempt at closure of the shunt during definitive repair was
      unsuccessful. An aortic endoluminal stent graft was deployed to definitively
      close the shunt. There was a subsequent normalization of pulmonary pressures
      following Potts shunt closure. The patient will now proceed with surgical aortic
      root repair and aortic valve replacement.

PMID- 16945830
TI  - Treatment strategies in myocardial bridging: a case report.
AB  - Myocardial bridging is one of the nonatherosclerotic causes of coronary artery
      disease and is characterized by muscles overlying the intramyocardial course of a
      major epicardial coronary artery segment, leading to systolic compression.
      Myocardial bridging is considered a benign condition in most cases, but has been
      associated with serious cardiac events such as myocardial infarction and sudden
      death. We discuss the case of a 63-year-old man who was admitted to our hospital
      with effort-induced angina, bradycardia, and left ventricular hypertrophy on
      electrocardiogram. On coronary angiography, we found significant myocardial
      bridging with total occlusion in the left anterior descending artery during
      systole. In patients with myocardial bridging, symptoms often manifest during
      exercise and with tachycardia. But it is interesting to note that our patient was
      bradycardic and became symptomatic with minimal effort. Thus, we thought that
      these emphasized its significance and affected treatment strategy.

PMID- 16945831
TI  - Peripheral devices for recanalizing a giant thrombosed aneurysmal coronary
      artery.

PMID- 16945832
TI  - Alterations in myocardial energy metabolism induced by the anti-cancer drug
      doxorubicin.
AB  - Doxorubicin and other anthracyclines are among the most potent chemotherapeutic
      drugs for the treatment of acute leukaemia, lymphomas and different types of
      solid tumours such as breast, liver and lung cancers. Their clinical use is,
      however, limited by the risk of severe cardiotoxicity, which can lead to
      irreversible congestive heart failure. There is increasing evidence that
      essential components of myocardial energy metabolism are among the highly
      sensitive and early targets of doxorubicin-induced damage. Here we review
      doxorubicin-induced detrimental changes in cardiac energetics, with an emphasis
      on the emerging importance of defects in energy-transferring and -signalling
      systems, like creatine kinase and AMP-activated protein kinase.

PMID- 16945833
TI  - On phytoplankton aggregation: a view from an IBM approach.
AB  - In this paper, we build up an individual-based model (IBM) that describes the
      aggregative behavior in phytoplankton. The processes in play at the individual
      level (an individual=a phytoplankton cell) are: a random dispersal, a
      displacement due to the net effect of cells present in a suitable neighborhood
      (spatial interactions) and a branching (cell division and death). The IBM model
      provides a virtual world where phytoplankton cells appear to form clusters. Using
      this model, we explore the spatial structure of phytoplankton and present some
      numerical simulations that help the understanding of the aggregation phenomenon.

PMID- 16945834
TI  - [Olfactory receptors and odour coding].
AB  - The first step of olfactory detection involves interactions between odorant
      molecules and neuronal protein receptors. Odour coding results from the
      combinatory activation of a set of receptors and rests on their clonal expression
      and olfactory neurone connexion, which lead to formation of a specific sensory
      map in the cortex. This system, sufficient to discriminate myriads of odorants
      with a mere 350 different receptors, allows humans to smell molecules that are
      not natural (new cooking flavours, synthetic chemicals...). The extreme olfactory
      genome diversity explains the absence of odour semantics. Olfactory receptors are
      also involved in cellular chemotaxis.

PMID- 16945835
TI  - Influences of the season and the habitat structure on the foraging ecology of two
      coua species in the western dry forest of Madagascar.
AB  - I studied the foraging ecology of Coquerel's Coua (Coua coquereli) and Giant Coua
      (Coua gigas), which occur in the dry forest in west Madagascar. This kind of
      forest is characterised by an alternating of a dry and a rainy season. The
      foraging behaviour was described in several dimensions: i.e. height and
      proportion of perching, rate of capture (estimating the food availability),
      foraging techniques, substrates used, type and size of the captured prey. Their
      foraging behaviour was different according to the season and to the proximity of
      water. Habitat structure was important to take in consideration to study their
      foraging behaviour. They tended to use the same pattern of techniques and
      substrates, but differed by the proportions they used these variables and also by
      the possibility to climb into the dense understorey vegetation. Seasonal
      variation has probably an important effect on the prey availability and the
      nature of prey captured. The diet of both species is also discussed. I suggest
      that change in habitat structure and resources levels could be important to take
      in consideration for the conservation of these forest birds.

PMID- 16945837
TI  - [Contribution of microscopic techniques to anatomical and morphological knowledge
      on Styrax officinalis L].
AB  - The aim of this study was to precise anatomical and morphological features of the
      species Styrax officinalis with the help of current microscopic techniques, those
      features being of interest as valuable taxonomic characters. Typical hairy
      structures were observed on all surfaces of the aerial organs and their location,
      density and size were specified. Moreover, we demonstrated the occurrence of
      secretory glands in the leaf blades. These structures were revealed for the first
      time for this species.

PMID- 16945836
TI  - [Physiological and structural modifications induced by cadmium-calcium
      interaction in tomato (Lycopersicon esculentum)].
AB  - Tomato seedlings (Lycopersicon esculentum), initially cultivated in a basic
      nutrient solution during 12 days, were treated with increasing CdCl(2)
      concentrations for 10 days. The results showed that cadmium inhibited the weight
      growth depending on the metal concentration and the plant organ. In the presence
      of 20 microM CdCl(2), the addition of calcium, 0.1 to 10 mM of CaCl(2) in the
      culture medium, improved especially the biomass production and the mineral
      composition of the plants in concomitance with an increase in the contents of
      photosynthetic pigments. Histological study at the hypocotyle level revealed that
      cadmium (20 microM) induced a restriction of the tissue territories as well as
      meristem formations differentiating in a root structure. At this concentration,
      the addition of CaCl(2) (5 microM) was characterized by an opposite effect with
      absence of meristem structures. The overall results suggest that the alteration
      of some plant growth process after exposure to cadmium can be attenuated by an
      adequate calcium contribution in culture medium.

PMID- 16945839
TI  - The growth capacity of bone marrow CD34 positive cells in culture is drastically
      reduced in a murine model of Down syndrome.
AB  - Human trisomy 21, Down syndrome (DS), is characterized by mental retardation. In
      addition, high risks of developing hematological and immune disorders, as well as
      cardiac, skeletal and other abnormalities are life-long concerns. Recent data
      suggested that bone marrow contains progenitors, hematopoietic or stromal cells,
      which may have the potential of generating non hematopoietic tissue such as
      neural cells, cardiac cells or osteoblasts. Therefore we have used a model of
      Down syndrome, Ts65Dn mice, to investigate their bone marrow. We have found that
      the vast majority of CD34(+) cells in the bone marrow of adult Ts65Dn mice, but
      not of the CD34(-) cells, exhibit a drastic reduction in their in vitro growth
      capacity. In addition to neural antigens, cultured CD34(+) cells from trisomic
      and diploid mice also expressed mast cell markers.

PMID- 16945838
TI  - Evolution of phosphoenolpyruvate carboxylase activity and lipid content during
      seed maturation of two spring rapeseed cultivars (Brassica napus L.).
AB  - Phosphoenolpyruvate carboxylase (PEPc: EC 4.1.1.31) activity was monitored during
      seed maturation of two varieties (Hybridol and Pactol) of rapeseed (Brassica
      napus L.), widely cultivated in Tunisia. In the Hybridol variety, PEPc activity
      did not exceed 5 micromol h(-1) per gram of fresh weight (FW) during the first
      stages of maturation. It then highly increased to reach more than 30 micromol h(
      1) g(-1)/FW. On the contrary, in the Pactol variety, the evolution of PEPc
      activity showed a classical curve, i.e. an increase during the most active phase
      of lipid accumulation in maturating seeds, followed by a rapid decrease until the
      end of seed maturation. In both varieties, the seed oil was characterised by a
      high content of oleic acid (C(18:1)), linoleic (C(18:2)) and linolenic acids
      (C(18:3)). Saturated fatty acids were also present, although decreasing with
      maturation course. The analysis of the triacylglycerols (TAG) showed that
      trioleoylglycerol (OOO) and dioleoyllinoleoylglycerol (OOL) were the major
      species (ca. 35% and ca. 25% of the total respectively). The evolution pattern of
      fatty acids and TAG contents was similar to that of PEPc activity. Taken
      together, our findings suggest that PEPc may be involved in fatty acid and
      triacylglycerol biosynthesis during seed maturation of both rapeseed varieties.

PMID- 16945840
TI  - Does coverage matter at mesoscale within a Posidonia oceanica seagrass meadow?
AB  - Despite the fact that coverage is one of the most widely used descriptors for
      seagrass meadows, the spatial structure of coverage at mesoscale has not often
      been taken into account. The present work investigates the structure of P.
      oceanica coverage at mesoscale and its possible relationship with several factors
      (depth, type of substrate, relative level within the meadow, type of shoot
      density and level of anthropic pressure). Five classes of coverage structure are
      delineated within P. oceanica meadows and statistical analysis of the data did
      not provide evidence of a link with the factors taken into consideration. This
      result could be explained by the prevailing role of endogenic processes in the
      structuring of the P. oceanica meadow.

PMID- 16945841
TI  - [Nitrogen fixation and primary production in Western Mediterranean].
AB  - Nitrogen fixation, nitrate assimilation and primary production ((13)C/(15)N
      method) were investigated during one year and half in the northwestern
      Mediterranean Sea. Nitrogen fixation was detectable all over the year with rates
      ranged from 2 to 17 nmol N l(-1) d(-1)(d). Highest values being obtained during
      spring associated with the phytoplankton bloom. High rates (4-8 nmol N l(-1) d(
      1)(d)) were also measured during summer, when primary productivity was very low.
      Then, diazotrophy process supplies significant new nitrogen during summer
      oligotrophic periods. This new nitrogen input can balance the annual nitrogen
      biogeochemical budget in the Mediterranean Sea and should explain the high
      nitrate/phosphate ratio observed in deep waters.

PMID- 16945842
TI  - Infection of Spodoptera frugiperda cells with Autographa californica nuclear
      polyhedrosis virus I. Synthesis of intracellular proteins after virus infection.
AB  - The replication of Autographa californica nuclear polyhedrosis virus (AcNPV) in
      Spodoptera frugiperda cells in culture has been studied with different methods.
      The first virus-induced polypeptides (with molecular weights of 46K, 30K, 29K) in
      infected cells appeared at 3 hr postinfection. Viral DNA synthesis started at
      about 5 hr postinfection. By electron microscopy, intranuclear nucleocapsids were
      detected at 10 hr postinfection and at about the same time, the titer of
      intracellular infectious particles began to rise. The pattern of viral protein
      synthesis was rather complex; within the first 24 hr postinfection, some 30-35
      different polypeptides appeared sequentially in infected cells. Some of these
      polypeptides seemed to be structural proteins of the virion. The 28K polyhedrin
      polypeptide was synthesized originally as a precursor and was modified
      posttranscriptionally. Polyhedrin was synthesized until late in infection. Two
      distinct stages exist in AcNPV replication: (i) the rapid synthesis of AcNPV
      specific nucleic acids and proteins and the assembly of nucleocapsids, some of
      which develop by budding to extracellular virus; (ii) intranuclear membrane
      synthesis, polyhedra formation, and occlusion of intranuclear, enveloped virions.

PMID- 16945843
TI  - Infection of Spodoptera frugiperda cells with Autographa californica nuclear
      polyhedrosis virus II. The viral DNA and the kinetics of its replication.
AB  - The kinetics of replication of Autographa californica nuclear polyhedrosis virus
      (AcNPV) DNA in Spodoptera frugiperda cells in culture were studied. Viral DNA
      replication started at about 5 hr postinfection, the rate of viral DNA
      replication reached a maximum at about 18 hr postinfection and thereafter
      decreased. Parental viral DNA could be detected within the first hour
      postinfection in the total intracellular DNA by the Southern technique. There was
      no evidence for the occurrence of AcNPV DNA sequences which became covalently
      linked to cellular DNA between 1 and 3 hr post-infection in the productive cycle.
      The AcNPV DNA appeared as a covalently closed circular molecule of about 92 x
      10(6) daltons. The AcNPV DNA did not seem to be methylated, at least there were
      no 5'-CmCGG3' sequences detectable in this DNA. Restriction enzyme analysis of
      viral DNA preparations derived from several single plaque isolates of AcNPV as
      well as of DNA from different virus stocks revealed a certain heterogeneity of
      the AcNPV DNA.

PMID- 16945844
TI  - Infectious DNA from Autographa californica nuclear polyhedrosis virus.
AB  - Cells from the lepidopteran Spodoptera frugiperda can be successfully transfected
      in culture with the DNA from Autographa californica nuclear polyhedrosis virus
      (AcNPV). The calcium chloride precipitation procedure has been used in
      conjunction with dimethyl sulfoxide treatment of the transfected cells. The
      highest specific infectivity observed was 6.1 x 10(4) PFU/mug of AcNPV DNA. As
      judged from a comparison of the restriction patterns of viral DNA preparations,
      the virus produced in transfection experiments was identical to the virions from
      which the DNA for transfection was prepared. The transfection procedure described
      will be useful for the genetic analysis of AcNPV DNA.

PMID- 16945846
TI  - [Management strategies for the treatment of non malignant chronic pain in the
      elderly].
AB  - Chronic pain has a growing incidence with age. In the elderly, the most frequent
      etiologies of pain are musculoskeletal diseases, neuropathic pain and cancer.
      Pain management in older patients requires a comprehensive assessment, adapted to
      the patient's cognitive functioning, using specific tools, and taking into
      account the daily life activities and autonomy. Management includes drugs,
      especially paracetamol and level 2 and 3 opioids. Non steroidal anti-inflammatory
      drugs (NSAIDs) should be avoided, including COX-2 inhibitors. Drugs are to be
      prescribed regularly, pre-emptively, and via oral route. Immediate release drugs
      should be selected, and a slow increase of dosages. Local treatments should be
      preferred: local injections, topical application and physiotherapy.
      Rehabilitation, pool-therapy, crenotherapy may be proposed. In conclusion,
      chronic pain management in elderly patients does not importantly differ from that
      in younger patients. Specificities are more related to the assessment of pain and
      to the drugs side effects rather than to the type of drugs.

PMID- 16945847
TI  - [Specificity of pain assessment in the aged].
AB  - Pain is frequent in older subjects but remains under diagnosed and treated.
      Systematic evaluation of pain is recent and the assessment tools, although well
      known, are only occasionally used. The main progress in the evaluation of pain in
      the elderly is the concept of behavioral assessment. Two assessment scales have
      been designed for people with communication disorders: the DOLOPLUS and the ECPA.
      Every carer should be skilled in the use of at least one auto and one hetero
      assessment scale to recognize and treat pain in the older subjects.

PMID- 16945848
TI  - [Anxiety disorders in the elderly: Clinical and therapeutic aspects].
AB  - Few studies have been specifically devoted to anxiety disorders in the elderly.
      Nevertheless, various factors can expose this population to relevant levels of
      anxiety: development of somatic disorders, bereavements, isolation, changes of
      life, use of anxiogenic drugs, etc. Prevalence rates weaker than in the general
      population are usually found, but with high rates, however, for generalized
      anxiety disorder and agoraphobia. The clinical aspect of these anxious states is
      often dominated by somatic symptoms and complaints, and some topics seem of
      special concern: fear of death and disease, displacement phobias related to the
      fear of falling or being attacked. Some consequences should be particularly
      watched over (diverse somatic affections, depression, dementia, and even suicidal
      tendencies), which justify an accurate clinical evaluation. Treatment must often
      be multidisciplinary involving medical but also psychological, and institutional
      aspects. The therapeutic strategies are largely identical to what they are in the
      other groups of age. Anxiolytic drugs and antidepressants, cognitive-behavioral
      therapies can be proposed, even if some adaptation of drug posology or methods of
      non pharmacological interventions should be needed. Particular attention should
      be paid to the risk of benzodiazepine dependence, drugs which are widely used by
      elderly subjects. As a conclusion, anxiety disorders in the elderly present
      clinical and therapeutic particularities, which require a special approach and
      the development of specific epidemiological, physiopathologic and therapeutic
      researches.

PMID- 16945849
TI  - [Primary progressive aphasia: clinical aspects].
AB  - Primary progressive aphasia (PPA), initially described by Mesulam, is a syndrome
      of progressive deterioration of language, occurring in the presenium. Several
      classifications have been proposed, but the most useful one distinguishes non
      fluent and fluent forms of PPA. Both begin by anomia. In non fluent PPA, there is
      a progressive reduction of language, sometimes with aggramatism and articulatory
      impairment, but without impairment of comprehension. Fluent PPA is characterized
      by preserved fluency with severe impairment of single word comprehension. It is
      frequently confounded with semantic dementia (SD), but some observations can be
      differentiated from SD. After several years, all patients become mute, and most
      of them develop dementia, usually of frontal lobe type. The syndrome of PPA is
      due to neurodegenerative brain pathology affecting mostly the perisylvian regions
      of the left hemisphere. In most cases, no Alzheimer type pathology was found in
      the brain, but tauopathy (mainly in non fluent PPA) or motor neuron disease type
      pathology - tau negative ubiquitin inclusions (mainly in fluent PPA). However,
      Alzheimer type pathology was found in a substantial number of cases.

PMID- 16945850
TI  - [Representation of medical drugs and factors involved in their consumption in the
      elderly].
AB  - The purpose of this paper is to introduce a research on the relationship that an
      aging person establishes with medical drugs. From data on the social perception
      of elderly people about health and medication, we have constructed a
      questionnaire which has been submitted to a sample of 94 elderly persons aged
      from 64 to 89 years. The factorial analysis brought into perspective five
      dimensions related to medication: social, dependency, normative, coping, feelings
      of security. Crossing these dimensions with the socio-demographic and medical
      variables allowed to identify some decisive factors for medical drug consumption.
      The results of the research show the complexity of medical drug consumption which
      is influenced by multiple variables. Furthermore the perception of medical drugs
      remains somewhat ambiguous; it is sometimes perceived as remedy and sometimes as
      poison. It is no longer considered a decisive factor for good health while aging.

PMID- 16945851
TI  - [Gait and dual-task: definition, interest, and perspectives in the elderly].
AB  - Walking is an automated rythmic motor behavior that is mostly controlled by
      subcortical brain regions. Automaticity implies that gait can be performed
      without attention. However, recent works highlight the involvement of attentional
      resources in gait, using a "dual-task" methodology in which performance on
      attention-demanding tasks such as spoken verbal response and walking is compared
      when they are performed separately and concurrently. Changes in gait patterns due
      to simultaneous performance of an attention-demanding task are interpreted as
      interference caused by competing demands for attentional resources involving the
      cortical level in gait control. Dual-task related gait changes are a new way to
      assess age-associated change in gait control. Furthermore, new screening tools of
      falling risk based on the dual-task paradigm have been developed, comparing
      walking performance alone to walking while performing a simultaneous attention
      demanding task. However, the consistent prediction of falls by dual-task testing
      remains difficult. The recent availability and growing number of validated, user
      friendly portable gait analysis systems allow simple objective gait measurement
      such as gait variability. The study of gait variability under dual-task
      represents a new challenge for the clinicians because high stride-to-stride
      variability is a powerful fall predictor in older adults. Because there is
      increasing evidence that age-related gait changes are associated with incidence
      of dementia, dual-task related gait changes could provide useful information
      about relationship between gait disorders and cognitive decline. Furthermore,
      dual-task could be a new approach of the gait disorders rehabilitation.

PMID- 16945852
TI  - [Role of personality, familial environment, and severity of the disease on the
      behavioral and psychological symptoms of dementia].
AB  - The phenomenology of Behavioral and Psychological Symptoms of Dementia (BPSD)
      occurring in the Alzheimer's disease and related syndromes remains not well
      known. The goal of this study was to assess the role of disorders of personality,
      psychiatric disorders and home environment in the occurence of the BPSD; 99
      inpatients from a short-term Alzheimer unit were included in the study. BPSD were
      assessed by the NeuroPsychiatric Inventory, the severity of dementia by the MMSE.
      Previous somatic, psychiatric and personality disorders were evaluated by a semi
      structured interview of the family, and classified according to the A, B and C
      groups from the DSM-IV. Eighty eight percent of the patients presented at least
      one BPSD. The patients whose the main caregiver was a spouse appeared to be more
      aggressive. Sixty seven per cent of the patients presented with former disorders
      of personality; they were more delirious, more anxious, more irritable and
      suffered more disorders of appetite. Each type of personality disorder modified
      the phenomenology of the BPSD. The severity of dementia does not seem sufficient
      to explain the occurrence of BPSD. Other factors seem to play a dominating part
      such as the previous disorders of personality and psychiatric antecedents.
      However, the exact links between disorders of personality, psychiatric
      antecedents and BPSD remain difficult to specify.

PMID- 16945853
TI  - Does word frequency affect lexical selection in speech production?
AB  - We evaluated whether lexical selection in speech production is affected by word
      frequency by means of two experiments. In Experiment 1 participants named
      pictures using utterances with the structure "pronoun + verb + adjective". In
      Experiment 2 participants had to perform a gender decision task on the same
      pictures. Access to the noun's grammatical gender is needed in both tasks, and
      therefore lexical selection (lemma retrieval) is required. However, retrieval of
      the phonological properties (lexeme retrieval) of the referent noun is not needed
      to perform the tasks. In both experiments we observed faster latencies for high
      frequency pictures than for low-frequency pictures. This frequency effect was
      stable over four repetitions of the stimuli. Our results suggest that lexical
      selection (lemma retrieval) is sensitive to word frequency. This interpretation
      runs against the hypothesis that a word's frequency exerts its effects only at
      the level at which the phonological properties of words are retrieved.

PMID- 16945854
TI  - How does running memory span work?
AB  - In running memory span, a list ends unpredictably, and the last few items are to
      be recalled. This task is of increasing importance in recent research. We argue
      that there are two very different strategies for performing running span tasks: a
      low-effort strategy in which items are passively held until the list ends, when
      retrieval into a capacity-limited store takes place; and a higher-effort strategy
      in which working memory is continually updated using rehearsal processes during
      the list presentation. In two experiments, we examine the roles of these two
      strategies and the consequences of two types of interference.

PMID- 16945855
TI  - The role of encoding in reality monitoring: a running memory test with
      Alzheimer's type dementia.
AB  - Reality monitoring refers to the discrimination between memories of internal and
      external events (e.g., Johnson & Raye, 1981). A total of 28 healthy older adults
      and 28 older adults with Alzheimer's type dementia (DAT) were asked to perform or
      to imagine performing simple action statements in a running memory test. This
      task required participants to tell whether the action statement had been carried
      out or imagined, or whether it was new at unpredictable intervals. The results
      indicated that older adults with DAT had greater difficulty in reality monitoring
      than did the healthy control group. The finding is discussed in terms of the role
      of working memory functions in reality monitoring.

PMID- 16945856
TI  - When do auditory/visual differences in duration judgements occur?
AB  - Four experiments examined judgements of the duration of auditory and visual
      stimuli. Two used a bisection method, and two used verbal estimation.
      Auditory/visual differences were found when durations of auditory and visual
      stimuli were explicitly compared and when durations from both modalities were
      mixed in partition bisection. Differences in verbal estimation were also found
      both when people received a single modality and when they received both. In all
      cases, the auditory stimuli appeared longer than the visual stimuli, and the
      effect was greater at longer stimulus durations, consistent with a "pacemaker
      speed" interpretation of the effect. Results suggested that Penney, Gibbon, and
      Meck's (2000) "memory mixing" account of auditory/visual differences in duration
      judgements, while correct in some circumstances, was incomplete, and that in some
      cases people were basing their judgements on some preexisting temporal standard.

PMID- 16945857
TI  - Differences in the types of musical regularity learnt in incidental- and
      intentional-learning conditions.
AB  - Several studies have found learning of biconditional grammars only under
      intentional rule-search conditions (e.g., Johnstone & Shanks, 2001). Memorization
      of strings merely led to the learning of chunks. We used a musical grammar, a
      diatonic inversion, that is a type of biconditional grammar. Participants either
      were required to memorize a set of grammatical tunes (incidental learning), or
      were asked to search for the underlying rule whilst being given feedback about
      their performance (intentional learning). The results showed that participants in
      the incidental-learning condition did not learn the inversion rule and merely
      acquired explicit knowledge about chunks. However, participants in the
      intentional-learning condition learnt both the inversion rule and chunks.

PMID- 16945858
TI  - Distance and ratio effects in the flanker task are due to different mechanisms.
AB  - When participants must respond to a relevant central target and ignore irrelevant
      flanking stimuli the flanking stimuli produce a compatibility effect, with
      increased response speed and accuracy on compatible as compared to incompatible
      trials. This flanker effect is larger when compatible trials are more frequent
      than incompatible trials (the ratio effect). A potential explanation of this
      ratio effect is that the occurrence of frequent incompatible trials causes the
      focus of spatial attention to be set narrower than when there are frequent
      compatible trials. The present investigation tests this hypothesis by comparing
      the flanker effect with near and far flankers. The hypothesis predicts that the
      flanker distance should modulate the ratio effect more when incompatible trials
      are frequent than when compatible trials are frequent. The results, however, show
      the opposite pattern: Distance effects are larger in conditions with frequent
      compatible trials. Moreover, the effect of distance but not the ratio effect was
      eliminated when flanker distance remained fixed across blocks of trials, and also
      when participants had to attend to flanker stimuli in a go-no-go task. These
      results suggest that the ratio effect does not result from an adjustment of the
      focus of spatial attention.

PMID- 16945859
TI  - Context effects of pictures and words in naming objects, reading words, and
      generating simple phrases.
AB  - In five language production experiments it was examined which aspects of words
      are activated in memory by context pictures and words. Context pictures yielded
      Stroop-like and semantic effects on response times when participants generated
      gender-marked noun phrases in response to written words (Experiment 1A). However,
      pictures yielded no such effects when participants simply read aloud the noun
      phrases (Experiment 2). Moreover, pictures yielded a gender congruency effect in
      generating gender-marked noun phrases in response to the written words
      (Experiments 3A and 3B). These findings suggest that context pictures activate
      lemmas (i.e., representations of syntactic properties), which leads to effects
      only when lemmas are needed to generate a response (i.e., in Experiments 1A, 3A,
      and 3B, but not in Experiment 2). Context words yielded Stroop-like and semantic
      effects in picture naming (Experiment 1B). Moreover, words yielded Stroop-like
      but no semantic effects in reading nouns (Experiment 4) and in generating noun
      phrases (Experiment 5). These findings suggest that context words activate the
      lemmas and forms of their names, which leads to semantic effects when lemmas are
      required for responding (Experiment 1B) but not when only the forms are required
      (Experiment 4). WEAVER++ simulations of the results are presented.

PMID- 16945860
TI  - Priming and binding in and across perception and action: a correlational analysis
      of the internal structure of event files.
AB  - Individual performance was compared across three different tasks that tap into
      the binding of stimulus features in perception, the binding of action features in
      action planning, and the emergence of stimulus-response bindings ("event files").
      Within a task correlations between the size of binding effects were found within
      visual perception (e.g., the strength of shape-location binding correlated
      positively with the strength of shape-colour binding) but not between perception
      and action planning, suggesting different, domain-specific binding mechanisms. To
      some degree, binding strength was predicted by priming effects of the respective
      features, especially if these features varied on a dimension that matched the
      current attentional set.

PMID- 16945861
TI  - Between reasoning.
AB  - In two experiments we investigated three-term reasoning with spatial relational
      assertions using the preposition between as compared to projective prepositions
      (such as to the left of). For each kind of assertion we distinguish the referent
      expression (i.e., the grammatical subject) from the relatum expression (i.e., the
      internal argument of the preposition; e.g., [The hedgehog]referent_expressionis
      to the left of [the frog]relatum_expression; [the snake]referent_expressionis
      between [the donkey and the deer]relatum_expression). Previous research has shown
      that integrating premises with projective prepositions is easier (a) when the
      relatum expression of the second premise denotes an element already given by the
      first premise (relatum = given), and (b) when the term denoting a given element
      precedes the term denoting a new element (given-new). Experiment 1 extended this
      finding to second premises with the preposition between. In Experiment 2, between
      figured in the first premise. In this case, participants built an initial
      preferred model already from the first premise, although such a premise is
      indeterminate with respect to the array that it describes. Since there is no need
      left for integrating the second premise, this premise is instead used to verify
      the initial model and to modify it when necessary. A further investigation of
      conclusion evaluation times showed that conclusions were evaluated faster when
      they first mentioned the element that was included most recently into the mental
      model of the premises. The use of premises with between permitted the separation
      of recency of model inclusion from recency of appearance of an element in a
      premise.

PMID- 16945862
TI  - Understanding spatial diagram structure: an analysis of hierarchies, matrices,
      and networks.
AB  - Abstract diagrams are powerful tools for comprehension and problem solving in
      diverse contexts. Two studies examined the structural properties of (i.e.,
      applicability conditions for) three interrelated spatial diagrams--hierarchies,
      matrices, and networks. College students from two groups with distinct
      educational backgrounds and learning histories--advanced computer science
      students and representative undergraduates--rated the diagnosticity of the
      hypothesized applicability conditions for each of the 3 diagrams. The results
      validated 24-26 of the 30 hypothesized applicability conditions and provided
      evidence regarding the relative importance, or diagnosticity, of the validated
      properties for each type of diagram. A different set of properties was identified
      as most highly diagnostic for each type of diagram, indicating that the three
      spatial diagrams are optimized to serve different representational functions: The
      matrix stores static information about the kind of relation that exists between
      pairs of items in different sets, the network conveys dynamic information by
      showing the local connections and global routes connecting the items being
      represented, and the hierarchy depicts a rigid structure of power or precedence
      relations among items. The quantitative and qualitative differences in
      representational knowledge due to educational background are discussed.

PMID- 16945864
TI  - Increasing the involvement of elderly patients in healthcare decision making--the
      IMPROVE study.

PMID- 16945865
TI  - Evaluation of an intervention designed to enhance involvement of older patients
      in their own care.
AB  - OBJECTIVE: To implement a programme for involvement of older patients aged 70+ in
      general practice, and to detect quality changes after its implementation.
      METHODS: The study was performed in 11 European countries as an uncontrolled
      before-and-after study, in which a number of GPs and patients answered a
      questionnaire before and after receiving an intervention. The intervention was
      aimed at motivating, instructing and facilitating GPs and older patients to
      increase patient involvement during consultation by use of a specially designed
      consultation leaflet. RESULTS: Valid data from seven countries exist. There was a
      total of 765 patients and 70 GPs in the pre-intervention phase, and 564 patients
      and 49 GPs in the post-intervention phase. In the post-intervention group, 43% of
      the patients thought that the consultation leaflet had improved the consultation
      and 62% of the GPs found it to be useful. There were no significant differences
      between pre- and post-intervention patient perceptions of the level of
      involvement, evaluations of consultations and perceptions of feeling enabled to
      deal with their health situation. CONCLUSION: Quality of consultations as
      measured by patient satisfaction and patient enablement did not improve as a
      result of the intervention, but nearly half of the patients and two thirds of the
      GPs found the intervention to be useful. Unselected use of this intervention on
      all patients cannot be advised without further studies on possible effects.
      Future studies should focus on the applicability and benefits of the methods for
      special patient groups.

PMID- 16945866
TI  - Patients' views on dyspepsia and acid suppressant drug therapy in general
      practice.
AB  - OBJECTIVES: To do an inventory on the opinion of long-term acid suppressant drug
      (ASD) users on their condition and drug treatment, and from that angle to reflect
      on possibilities to reduce usage and costs of long-term acid suppressant drug
      therapy. METHODS: In the year 2001, in seven general practices, patients who
      chronically used ASDs without proper indication were identified. A postal
      questionnaire based on the literature was sent to these patients (n=498).
      RESULTS: 318 (64%) returned questionnaires were fit for analysis. Patients
      experienced dyspepsia as unpleasant and restraining, and were extremely positive
      about ASDs without differences between H2-receptor antagonists (H2RAs) and proton
      pump inhibitors (PPIs). ASD use was very compliant. Patients smoked and drank
      less than the normal population. They did not continue unhealthy habits simply
      because ASDs enable them to. Most patients were not motivated to stop their ASDs.
      CONCLUSION: Dyspeptic complaints should not be underestimated. Improving
      lifestyle is not likely to generate much effect on ASD use. Due to a lack of
      motivation, discontinuing long-term ASD use may not be an efficient way to reduce
      the use and costs of ASDs. Patient-centred possibilities are prescribing H2RAs
      instead of PPIs as a first step, as they are perceived by patients to be equally
      effective, and encouraging patients to self-regulate drug treatment through on
      demand regimes.

PMID- 16945867
TI  - Out-of-hours co-operatives: general practitioner satisfaction with governance and
      working arrangements.
AB  - OBJECTIVE: General practice co-operatives have led to significant improvements in
      quality of life for general practitioners. Little is known about general
      practitioners' own experiences with the working arrangements and governance of co
      operatives. This study investigates GP satisfaction, the working environment,
      governance and future developments in co-operatives. METHODS: A questionnaire was
      sent to GPs in two co-operatives in the Republic of Ireland, covering mixed urban
      and rural areas. RESULTS: Of 221 GPs in the co-operatives, 82% responded and
      confirmed the co-operatives' positive effects on their lives. However, 57% still
      received requests for out-of-hours care while off duty, most commonly from
      patients who preferred to see their own doctor. Half felt overburdened by out-of
      hours work, especially those over 40 y of age. Twenty-five per cent were
      dissatisfied with the GP complaints mechanism. The majority (63%) would prefer a
      GP/health board partnership for the organization of out of hours, while 23%
      wanted sole responsibility. GPs indicated a strong need for better ancillary
      services such as nursing, mental health, dentistry, pharmacy and social work.
      Access to records is an important issue in terminal care and mental illness.
      CONCLUSION: While GP co-operatives are a success story for general practice, they
      will work better for general practitioners and their patients if nursing, mental
      health, dentistry, pharmacy and social services are improved. Support and
      training is needed in mental health, palliative and emergency care to increase
      competence and reduce stress. GPs are willing to work with health authorities in
      further co-operative development. More attention needs to be paid to the
      complaints and suggestions of GPs in the running and governance of their co
      operatives.

PMID- 16945868
TI  - A study of cardiovascular risk in overweight and obese people in England.
AB  - OBJECTIVES: To report current levels of obesity and associated cardiac risk using
      routinely collected primary care computer data. METHODS: 67 practices took part
      in an educational intervention to improve computer data quality and care in
      cardiovascular disease. Data were extracted from 435,102 general practice
      computer records. 64.3% (229,108/362,861) of people age 15 y and older had a body
      mass index (BMI) recording or a valid height and weight record that enabled BMI
      to be derived. Data about cardiovascular disease and risk factors were also
      extracted. The prevalence of disease and the control of risk factors in the
      overweight and obese population were compared with those of normal body weight.
      RESULTS: 56.8% of men and 69.3% of women aged over 15 y had a BMI record. 22% of
      men and 32.3% of women aged 15 to 24 y were overweight or obese; rising each
      decade to a peak of 65.6% of men and 57.5% of women aged 55 to 64 y. Thereafter,
      the proportion who were overweight or obese declined. The prevalence of ischaemic
      heart disease, diabetes mellitus and hypertension rose with increasing levels of
      obesity; their prevalence in those who are moderately obese was between two and
      three times that of the general population. Systolic and diastolic blood
      pressure, blood glucose even in non-diabetics, cholesterol and triglycerides were
      all elevated in the overweight and obese population. CONCLUSION: Based on the
      recorded data over half of men and nearly half of women are overweight or obese.
      They have increased cardiovascular risk, which is not adequately controlled by
      current practice.

PMID- 16945869
TI  - Western European best practice in primary healthcare.

PMID- 16945870
TI  - Do influenza and acute respiratory infective diseases weigh heavily on general
      practitioners' daily practice?
AB  - OBJECTIVE: Respiratory infections are a frequent causes of medical attendance.
      Influenza viruses increases this phenomena. The aim of this study was to
      prospectively identify GPs' increased work in terms of visits and time. METHODS:
      Over a period of five months 5 GPs recorded sex, age, number and place of visits,
      telephone consultations of the patients visited for acute respiratory disease
      (ARD)which included acute respiratory infections (ARI), influenza (FLU) and
      Influenza-like illness (ILI). Upper respiratory tract infections (URTI) were
      classified as sinusitis, rhinitis, otitis, tonsillitis, pharyngitis, laryngitis,
      Lower respiratory tract infections (LRTI) were classified as tracheitis,
      bronchitis, pneumonia, bronchopneumonia, acute episodes of chronic obstructive
      pulmonary disease (COPD) and asthma. FLU and ILI were considered two different
      entities on the basis of symptoms. RESULTS: Acute respiratory disease increase of
      22 patients attending every GP's office monthly (from 176 to 198 total visits).
      6,542 patients were observed. The incidence of ARD was 33.5% (2191: 1,091 female
      and 1,100 males). URTI affected 944 patients, LRTI 739, FLU 328 and ILI 180. The
      increase in home visits grew from 10 to 36. Each home visit took from 15 to 45
      minutes. In a high number of cases (236), home visits were necessary for sick
      leave certificates. FLU (54%) and LRTI (37.5%) required more attention, and they
      were the primary causes for visits. Telephone consultations took place for all
      ILI or FLU of minor severity and in young people. CONCLUSION: During the winter
      there is an increased work-load for GPs due to the diffusion of influenza virus
      and respiratory tract diseases. "Burn out syndrome" is increasing among the GPs.
      Territorial GPs' action is highly efficacious. Patients self-certification should
      be evaluated. Vaccine therapy could be more effective if done on a larger
      population. More research is needed.

PMID- 16945871
TI  - Do co-existing psychosocial problems influence the prescription of psychotropic
      medication in depressive and anxiety disorders?

PMID- 16945872
TI  - Is the expression "Oh, by the way ..." a problem that arises in the early moments
      of a consultation?

PMID- 16945873
TI  - Hypertension management in primary care in Iceland.

PMID- 16945874
TI  - Academic outreach: fostering learning and research in general practice.

PMID- 16945876
TI  - Medical renaissance in Florence.

PMID- 16945877
TI  - Assessing chronic pain in general practice: are guidelines relevant? A cluster
      randomized controlled trial.
AB  - OBJECTIVES: To evaluate the impact of using pain assessment scales on the
      management of musculoskeletal chronic pain. METHODS: Cluster-randomized
      controlled multicentre trial in French general practice settings. Practices were
      randomized by region before patient recruitment. The inclusion concerned patients
      suffering from musculoskeletal chronic pain. General practitioners assigned to
      the scale group used two validated assessment instruments; those assigned to the
      control group cared for their patients according to their usual practice. The
      primary end-point was the level of relief obtained and the secondary changes in
      prescription of painkilling modalities. RESULTS: A total of 155 general
      practitioners included 772 successive patients suffering from musculoskeletal
      chronic pain. The control group reported a mean level of relief of 50.7% compared
      with one of 41.1% in the scale group (p<0.0001). In the intervention group,
      physicians decreased significantly their prescription of level two painkillers.
      CONCLUSIONS: In general practice, the use of pain assessment scales is not
      associated with greater pain relief. The lesser level of pain relief obtained in
      the scale group does provide evidence that using pain assessment scales does not
      enhance the relief of chronic pain in patients in primary care. Guidelines which
      recommend the systematic use of scales for the assessment and monitoring of
      chronic pain are not tailored to either the context or the patients encountered
      in the primary care setting.

PMID- 16945878
TI  - Diabetes mellitus in Irish general practice: level of care as reflected by HbA1c
      values.
AB  - OBJECTIVE: To assess the level of care given to people with diabetes by general
      practitioners and factors affecting it. METHODS: A cross-sectional study of Irish
      general practitioners, looking at practice characteristics and patient care over
      the previous 2 years; a nationally representative sample of 27 general
      practitioners. A total of 1030 people with diabetes were studied, of whom 201
      were type 1 and 829 were type 2. RESULTS: The response rate was 27 out of 52
      (52%). HbA1c values were not related to the patient's socioeconomic status. The
      average HbA1c for type 1 people with diabetes was 7.81%, and for type 2 it was
      7.1%. HbA1c values were measured 3.02 times for type 1 and 3.16 times for people
      with type 2 diabetes. This is a good standard of care, especially for type 2
      disease. Computerized practices and those patients whose care was shared with the
      hospital achieved better control, even though HbA1c levels were checked less
      frequently with computerization. The use of a protocol in the practices also
      improved care. Those practices employing a nurse had increased frequency of
      measurement of HbA1c and better control on univariate but not on multivariate
      analysis. Possible reasons for this are discussed. CONCLUSION: Diabetes Mellitus
      is treated to a good standard in Irish general practice, especially type 2
      disease. This standard appears to be independent of the patient's socio-economic
      status, is improved by GPs being computerised, in group practices and by
      providing care according to a protocol. Shared care also improves control.
      Employing a practice nurse may also improve care.

PMID- 16945879
TI  - Experience of intimate partner violence among women and men attending general
      practices in Dublin, Ireland: a cross-sectional survey.
AB  - This cross-sectional study examined women's and men's reported experience of
      intimate partner violence in general practice in the greater Dublin region. A
      high prevalence of reported experience of controlling behaviour and violent
      incidents was found. Although the reported prevalence of both was higher in men,
      women were more likely to have reported fear of a partner and a severe level of
      violence. CONCLUSION: The findings demonstrate that intimate partner violence is
      a major problem among the men and women surveyed.

PMID- 16945880
TI  - Cluster randomized controlled trials in primary care: an introduction.
AB  - BACKGROUND: Cluster randomized trials occur when groups or clusters of
      individuals, rather than the individuals themselves, are randomized to
      intervention and control groups and outcomes are measured on individuals within
      those clusters. Within primary care, between 1997 and 2000, there has been a
      virtual doubling in the number of published cluster randomized trials. A recent
      systematic review, specifically within primary care, found study quality to be
      both generally lower than that reported elsewhere and not to have shown any
      recent quality improvement. OBJECTIVE: To discuss the design, conduct and
      analysis of cluster randomized trials within primary care in terms of the
      appropriate expertise required, potential bias, ethical considerations and
      expense. DISCUSSION: Compared with trials that involve the randomization of
      individual participants, cluster randomized trials are more complex to design and
      analyse and, for a given sample size, have decreased power and a broadening of
      confidence intervals. Cluster randomized trials are specifically prone to
      potential bias at two levels-the cluster and individual. Regarding the former, it
      is recommended that cluster allocation be undertaken by a party independent to
      the research team and careful consideration be given to ensure minimal cluster
      attrition. Bias at the individual level can be overcome by identifying trial
      participants before randomization and at this time obtaining consent for
      intervention, data collection or both. A unique ethical aspect to cluster
      randomized trials is that cluster leaders may consent to the trial on behalf of
      potential cluster members. Additional costs of cluster randomized trials include
      the increased number of patients required, the complexity in their design and
      conduct and, usually, the need to recruit clusters de novo. CONCLUSION: Cluster
      randomized trials are a powerful and increasingly popular research tool. They are
      uniquely placed for the conduct of research within primary-care clusters where
      intracluster contamination can occur. Associated methodological issues are
      straightforward and surmountable and just need careful consideration and
      management.

PMID- 16945881
TI  - Information in a Dutch GP registration system about high risks on long-lasting
      sickness absence: a cross sectional exploration in their registration system.

PMID- 16945882
TI  - Marketing of a new non-sedating antihistamine (fexofenadine) puts an additional
      burden on healthcare system resources in Israel.

PMID- 16945883
TI  - Course of glycaemia in poorly controlled type 2 diabetes patients 2.5 years after
      optimizing oral treatment in general practice.

PMID- 16945884
TI  - Healthcare utilization is substantial for patients with type 2 diabetes in
      primary care: a patient-level study in a Swedish municipality.

PMID- 16945885
TI  - Diet and weight gain of elderly diabetic patients.

PMID- 16945886
TI  - Patients with irritable bowel syndrome in Swedish primary care.

PMID- 16945889
TI  - Moral values and career: factors shaping the image of healthy work for female
      dentists.
AB  - OBJECTIVE: Female unpromoted general practice dentists (GPDs) constitute about
      one-quarter of all dentists in Sweden. These female dentists suffer from many
      problems relating to their psychosocial working conditions. There are wide
      discrepancies between their perception of the ideal job situation and reality.
      Previously, three factors were found to constitute the ideal job situation. The
      aim of this study was to analyze patterns in two of these factors, i.e. the moral
      and the career factors, for understanding how ideal circumstances are conceived,
      i.e. how "good work" for the dentists could be obtained. MATERIAL AND METHODS: In
      the year 2000, all female unpromoted GPDs (183 persons) within the Public Dental
      Health Service (PDHS) in a region in Sweden received a questionnaire; response
      rate 94%. Four multiple regression models were constructed for two factors of
      good work and for the differences between the ideal job situation and reality
      concerning these factors. RESULTS: In all models, the explained variance was
      high. Those dentists who were committed to moral issues perceived large
      differences between the ideal and reality concerning moral values. Dentists
      committed to career issues experienced large differences between the ideal and
      reality concerning career development. Those dentists - about 60% - who would not
      want to be a dentist if they were to choose today, perceived large discrepancies
      concerning moral and career issues. CONCLUSIONS: The PDHS organization has failed
      to convince or engage those whom it ought to engage, that is those with the
      highest level of commitment. Dentists' emphasis on moral values confirms the
      character of dentistry as primarily a human service work.

PMID- 16945890
TI  - Healing following ultrasonic debridement and PVP-iodine in individuals with
      severe chronic periodontal disease: a randomized, controlled clinical study.
AB  - OBJECTIVE: Antiseptics and antibiotics delivered either locally or systemically
      have been used as an adjunct to scaling and root planing procedures in order to
      control the subgingival biofilm and thereby enhancing the treatment outcome. The
      results presented in the literature are, however, inconclusive. Povidone-iodine
      (PVP-iodine) has a bactericidal effect and is effective against most bacteria,
      including putative periodontal pathogens. The aim of the present study was to
      evaluate the clinical effect of PVP-iodine as an adjunct to ultrasonic scaling in
      the treatment of severe chronic periodontitis. MATERIAL AND METHODS: Twenty
      patients were recruited to the study. Each test site and the related quadrant
      were randomly assigned to one of four different treatment modalities: ultrasonic
      scaling + subgingival irrigation with 0.5% PVP-iodine for 5 min/tooth, ultrasonic
      scaling + subgingival irrigation with sterile saline solution for 5 min/tooth,
      subgingival irrigation with sterile saline solution for 5 min/tooth, and
      subgingival irrigation with 0.5% PVP-iodine for 5 min/tooth. The individuals were
      followed longitudinally for 6 months. RESULTS: The present study showed that non
      surgical periodontal therapy by means of an ultrasonic device was effective in
      attaining a healthy periodontal status in patients with severe periodontal
      lesions. No additive effect was found when PVP-iodine was included. CONCLUSIONS:
      Ultrasonic debridement using Odontogain is effective in controlling infection in
      patients with severe chronic periodontitis. PVP-iodine does not add any clinical
      benefit to the ultrasonic debridement alone under these circumstances.

PMID- 16945891
TI  - Risk factors and risk indicators associated with high caries experience in
      Swedish 19-year-olds.
AB  - OBJECTIVE: To study the risk factors and risk indicators associated with high
      caries experience (DMFS >or= 10) in 19-year-olds. MATERIAL AND METHODS: The
      subjects (n=800) lived in seven suburbs of Stockholm and answered a structured
      questionnaire about their parents' education, occupation, and country of birth,
      as well as their dietary habits, oral hygiene habits, and attitudes to dental
      care. Dental caries was assessed by clinical and radiographic examination using
      the decayed, missing, filled teeth (DMFT), and surfaces (DMFS) indices. Dental
      plaque (VPI%) and gingival bleeding (GBI%) indices were recorded. RESULTS: A
      total of 696 subjects (364 M, 332 F) participated in the study. The mean DMFT and
      DMFS were 3.9 and 5.1, respectively. In 81% of subjects, the DMFT was >or= 1 and
      15% had DMFS >or= 10. In the multivariate analysis, the variables significantly
      associated with high caries experience were: dental fear (p<0.001, odds ratio
      (OR) 2.8), GBI >or= 15% (p=0.003, OR 2.1), mother born abroad (p=0.007, OR 2.0)
      and irregular toothbrushing at night (p=0.008, OR 1.9). When all significant
      variables in the multivariate analysis were present, the cumulative probability
      of DMFS >or= 10 was 52%. CONCLUSIONS: Dental fear, gingival inflammation, a
      foreign-born mother, and irregular toothbrushing at night are variables that are
      strongly associated with high caries experience in 19-year olds. The study
      indicates that foreign-born parents, oral hygiene habits, and behavioral factors
      still have a strong impact on dental health in late adolescence.

PMID- 16945892
TI  - Knowledge of prescribing antimicrobials among Yemeni general dentists.
AB  - OBJECTIVE: Overuse of antimicrobial agents is closely related to an increase in
      bacterial resistance. A sound knowledge of appropriate prescribing of
      antimicrobials among health professionals is thus critical in combating the
      resistance. The objectives of this study were to assess the rationale for and
      patterns of antimicrobial prescriptions by general dental practitioners in Yemen.
      MATERIAL AND METHODS: A questionnaire containing 65 closed questions was used for
      this cross-sectional study and distributed to 280 dentists in the three major
      governorates in Yemen. The anonymously completed questionnaires sought answers to
      demographic questions and to questions on the therapeutic and prophylactic use of
      antimicrobial agents in dentistry. Correct and incorrect answers were defined
      according to information available in the current authoritative literature. Each
      correct answer was given a score of 1 while an incorrect answer scored 0. Thus,
      the total score had an attainable range from 0 to 65. Frequencies, means, and
      associations were assessed statistically. RESULTS: Out of 181 collected forms
      (response rate 64.6%), 150 were appropriately completed and used for data
      analyses. Penicillins were the most frequently prescribed drugs (72%), followed
      by spiramycin (10%). It was found that up to 84% of practitioners were likely to
      prescribe an antimicrobial agent when there was no clinical indication for such a
      medication. Many respondents (70%) would consider antibiotics for at least one of
      the given non-clinical factors. CONCLUSIONS: The results suggest that dental
      practitioners in Yemen lack uniformity in the rationale for appropriate
      prescribing of antimicrobials to their patients. Consequently, to reduce overuse,
      there is an urgent need for the dental community in the country to be informed
      about evidence-based guidelines and the appropriate use of antimicrobial agents
      in clinical dental practice.

PMID- 16945893
TI  - Fiber-reinforced composite substructure: load-bearing capacity of an onlay
      restoration.
AB  - OBJECTIVE: To determine the static load-bearing capacity of composite resin onlay
      restorations made of particulate filler composite (PFC) with two different types
      of fiber-reinforced composite (FRC) substructures. MATERIAL AND METHODS:
      Specimens were prepared to simulate an onlay restoration, composed of a 2 to 3 mm
      FRC layer as the substructure (short random and continuous bidirectional fiber
      orientation) and a 1 mm surface layer of PFC. Control specimens were prepared
      from plain PFC. The specimens were incrementally polymerized with a hand-light
      curing unit for 40 s and then post-cured in a light-curing oven for 15 min. The
      specimens were cemented on dentin substrate of extracted human molars using a
      standard adhesive resin cementation technique. The specimens (n=8/group) were
      water stored either for 24 h at room temperature or for 4 weeks at 37 degrees C
      before they were statically loaded until fracture using a universal testing
      machine. Failure modes were visually examined. RESULTS: ANOVA revealed that all
      specimens with FRC substructures had higher values of static load-bearing
      capacity than those obtained with plain PFC (p<0.001). The load-bearing capacity
      of all the specimens decreased after water storage (p<0.001). CONCLUSIONS:
      Restorations made from a combination of FRC and PFC showed better load-bearing
      capacity than those obtained with PFC alone.

PMID- 16945894
TI  - Parental influence on children's oral health-related behavior.
AB  - OBJECTIVE: The aim of this study was to determine whether there are differences
      between oral health-related knowledge, attitudes, beliefs and behaviors of
      children and their parents, and to identify the family-related factors associated
      with children's poor or good oral health-related behavior. MATERIAL AND METHODS:
      The data were gathered by means of questionnaires from 11-12-year-old
      schoolchildren and their parents who replied without having knowledge of the
      answers of the others. Differences between subgroups of children were analyzed by
      cross-tabulation, and the factors related to children's good or poor oral health
      related behavior by logistic regression analyses. RESULTS: Parents of children
      who reported good oral health-related behavior had better knowledge and more
      favorable behaviors than those of other parents. Predictors for a child's poor
      oral health-related behavior were the child's poor knowledge, male gender, the
      parent's frequent consumption of sweets, and the parent's infrequent use of
      xylitol gum. When a less strict threshold for the child's poor oral health
      related behavior was used, more predictors entered the model: the parent's
      unfavorable use of fluoride toothpaste; among girls, the parent's lack of
      knowledge; and among children whose mother's occupation level was high, the
      parent's infrequent use of xylitol gum. The parents of children whose oral health
      behavior was favorable were more likely to have a high level occupation and
      favorable oral health-related behaviors. CONCLUSIONS: Oral health-related
      knowledge of children and their parents seems to be associated with children's
      oral health-related behavior. Parents' behaviors, but not attitudes, were
      associated with children's oral health behavior.

PMID- 16945895
TI  - Bonding of lithium-disilicate ceramic to enamel and dentin using orthotropic
      fiber-reinforced composite at the interface.
AB  - OBJECTIVE: To evaluate the effect of orthotropic fiber-reinforced composite (FRC)
      at the interface on bonding of lithium-disilicate ceramic to dentin and enamel
      using different adhesive systems. MATERIAL AND METHODS: Dentin and enamel
      surfaces were ground occlusally on human molar teeth. Ceramic blocks of IPS
      Empress 2 (Ivoclar-Vivadent) were fabricated. Following acid etching and silane
      treatment of the ceramics, the teeth were divided into two groups (dentin and
      enamel). Ceramic blocks were bonded to the tooth substance with or without a
      layer of FRC and dual-polymerizing composite cement (Duolink). Total-etching
      (etchant (Etch 37) with adhesive (One Step Plus)) and self-etching (self-priming
      etchant (Tyrian SPE) with adhesive (One Step Plus)) systems were used, with five
      test specimens in each group. The cement was polymerized with a LED curing unit
      (Elipar Freelight LED 2) with standard mode of 40 s. The specimens were
      thermocycled for 6000 cycles and tested with the microtensile tester at a rate of
      5 mm/min. Fracture mode analyses were done by light microscope and with SEM. The
      data were analyzed using three-way analysis of variance (ANOVA). RESULTS: ANOVA
      showed that enamel had statistically significant (p<0.001) higher bond strength
      values than dentin. Bond strength values were significantly higher (p=0.012) with
      the total-etching system than with the self-etching system. The existence of FRC
      also had a minor effect on bond strength values (p=0.013). CONCLUSIONS: The
      enamel and total-etching system provided more reliable bonding than dentin and
      the self-etching system. Use of an FRC layer at the interface did not improve
      bond strength values, but instead changed fracture pattern behavior.

PMID- 16945896
TI  - Psychological factors and responses to artificial interferences in subjects with
      and without a history of temporomandibular disorders.
AB  - OBJECTIVE: It has often been suggested that psychological factors play a role in
      temporomandibular disorders (TMD). However, reports on psychological factors in
      TMD patients and controls have been equivocal. In a previous double-blind
      randomized controlled study, subjects with a TMD history showed more clinical
      signs and subjective symptoms and adapted less well to the artificial
      interferences than subjects without an earlier TMD history. In the present study,
      we analyzed the associations of psychological factors with symptom responses and
      adaptation to interferences. MATERIAL AND METHODS: Before the intervention, the
      subjects filled in questionnaires dealing with personality traits, level of
      psychological and somatic stress symptoms, coping strategies, and health beliefs.
      Every day during the 2-week follow-up period, the subjects rated the intensity of
      their symptoms on 9 modified visual analog scales (VAS). RESULTS: Health
      hardiness, positive socialization history and inhibition of aggression were
      associated with weaker symptom responses and better adaptation to true artificial
      interferences. Some personality characteristics in subjects with an earlier TMD
      history tended to associate with higher symptom reporting despite the type of
      intervention. CONCLUSIONS: Psychological factors appeared significant for the
      symptom responses to artificial interferences, and they seem to play a different
      role in responses in subjects with an earlier TMD history compared to those
      without.

PMID- 16945897
TI  - Relationship between bond strength and marginal and internal adaptation of
      composite restorations photocured by different methods.
AB  - OBJECTIVE: This study evaluated the relationship between bond strength and
      marginal and internal adaptation of composite restorations photocured using
      different methods with a quartz-tungsten-halogen light. MATERIAL AND METHODS: A
      push-out test was performed to evaluate bond strength of conical restorations in
      50 bovine incisors. To evaluate marginal (external) and internal restoration
      adaptation, 50 circular all-enamel margin preparations were done in bovine
      incisors. For both tests, the preparations were filled with Esthet*X resin
      composite. Specimens were distributed into 5 groups (n=10) depending on
      photoactivation method: G1: continuous light 700; G2: continuous light 150; G3:
      soft-start; G4: intermittent light; and G5: pulse-delay. The energy density for
      each method was standardized: 14 J/cm2. Caries Detector (Kuraray) was placed in
      restoration margins for detection of marginal adaptation. The percentage of
      interfaces present as gaps was determined using digital images. Specimens were
      then sectioned, stained, and the internal adaptation was recorded in a similar
      manner. Data were submitted to ANOVA and the Tukey HSD test, pre-set alpha =
      0.05. RESULTS: Bond strength G5 (7.2 MPa+/-1.3) was significantly greater
      (p=0.00280) than G1 (4.6 MPa+/-1.5). G2, G3, and G4 showed equivalent,
      intermediate strength values. No significant difference was found in marginal
      adaptation of any of the groups (p=0.16911). Internal adaptation results were the
      inverse of strength results: G5 (2.8%+/-4.9) showed significantly less
      (p=0.00979) gap formation compared to G1 (10.1%+/-6.2). CONCLUSION: Some
      modulated photocuring methods can increase bond strength while decreasing
      internal gap formation. An inverse relationship was found between push-out bond
      strength and internal adaptation. Marginal adaptation was not affected by any
      photoactivation method.

PMID- 16945898
TI  - Salivary mutans streptococci and lactobacilli levels after ingestion of the
      probiotic bacterium Lactobacillus reuteri ATCC 55730 by straws or tablets.
AB  - OBJECTIVE: Previous studies have suggested that lactobacilli-derived probiotics
      in dairy products may affect oral ecology, but the impact of different vehicles
      of ingestion has received little attention. The aim of the present study was to
      investigate the effect of the probiotic bacterium Lactobacillus reuteri ATCC
      55730 on the levels of salivary mutans streptococci and lactobacilli in young
      adults when ingested by two different delivery systems. MATERIAL AND METHODS: The
      material comprised 120 healthy young adults (21-24 years) and a placebo
      controlled study design with parallel arms was utilized. The subjects were
      randomly assigned to four equally sized groups: group A drank 200 ml of water
      through a prepared straw containing L. reuteri ATCC 55730 once daily for 3 weeks,
      while group B took 200 ml water through a placebo straw during the same period.
      Group C was given one tablet containing L. reuteri ATCC 55730 once daily for 3
      weeks, while group D received placebo tablets without bacteria. Salivary mutans
      streptococci and lactobacilli were enumerated with chair-side kits at baseline
      and 1 day after the final ingestion. RESULTS: A statistically significant
      reduction of the mutans streptococci levels was recorded after ingestion of the
      probiotic bacteria via the straw (p<0.05) and the tablets (p<0.01), which was in
      contrast to the placebo controls. A similar but non-significant trend was seen
      for lactobacilli. CONCLUSIONS: A short-term daily ingestion of lactobacilli
      derived probiotics delivered by prepared straws or lozenges reduced the levels of
      salivary mutans streptococci in young adults.

PMID- 16945899
TI  - Temporomandibular disorders, headaches, and cervical pain among females in a Sami
      population.
AB  - OBJECTIVE: The aim of this study was to examine the prevalence and co-morbidity
      of long-standing, intense, and frequent symptoms of pain and dysfunction in the
      jaw-face, head, and cervical region among adult females drawn from the Sami
      population in northern Sweden. METHODS: A total of 487 females, taken from the
      register of the Swedish Sami Parliament or registered as reindeer owners or
      reindeer herders in the Swedish Board of Agriculture and living in the Arctic
      region of northern Sweden, participated in a questionnaire study. RESULTS: The
      prevalence of pain and/or dysfunction in the jaw-face region was 32%, of
      headaches 61%, and of pain in the cervical region 56%. When the criterion of
      frequent symptoms (once a week or more often) was used, prevalence dropped to
      17%, 19%, and 30%, respectively, and when that of intense symptoms, defined as 5
      or more on an 11-point numerical rating scale, was added, prevalence dropped
      further to 8%, 11%, and 20%, respectively. The majority reported long-standing
      symptoms (67-98% depending on symptom). A high statistically significant
      relationship was found between frequent symptoms of pain and/or dysfunction in
      the jaw-face, frequent headaches, and frequent cervical pain (p<0.0001).
      CONCLUSIONS: Symptoms in the jaw-face, headaches, and cervical pain were
      frequently reported among a sample of Sami females living in the Swedish Arctic
      region. The prevalence of symptoms was strongly dependent on criteria of
      frequency and intensity.

PMID- 16945900
TI  - Phosphorylation of actin Tyr-53 inhibits filament nucleation and elongation and
      destabilizes filaments.
AB  - Dictyostelium actin was shown to become phosphorylated on Tyr-53 late in the
      developmental cycle and when cells in the amoeboid stage are subjected to stress
      but the phosphorylated actin had not been purified and characterized. We have
      separated phosphorylated and unphosphorylated actin and shown that Tyr-53
      phosphorylation substantially reduces actin's ability to inactivate DNase I,
      increases actin's critical concentration, and greatly reduces its rate of
      polymerization. Tyr-53 phosphorylation substantially, if not completely, inhibits
      nucleation and elongation from the pointed end of actin filaments and reduces the
      rate of elongation from the barbed end. Negatively stained electron microscopic
      images of polymerized Tyr-53-phosphorylated actin show a variable mixture of
      small oligomers and filaments, which are converted to more typical, long
      filaments upon addition of myosin subfragment 1. Tyr-53-phosphorylated and
      unphosphorylated actin copolymerize in vitro, and phosphorylated and
      unphosphorylated actin colocalize in amoebae. Tyr-53 phosphorylation does not
      affect the ability of filamentous actin to activate myosin ATPase.

PMID- 16945901
TI  - Familial ALS-superoxide dismutases associate with mitochondria and shift their
      redox potentials.
AB  - Recent studies suggest that the toxicity of familial amyotrophic lateral
      sclerosis mutant Cu, Zn superoxide dismutase (SOD1) arises from its selective
      recruitment to mitochondria. Here we demonstrate that each of 12 different
      familial ALS-mutant SOD1s with widely differing biophysical properties are
      associated with mitochondria of motoneuronal cells to a much greater extent than
      wild-type SOD1, and that this effect may depend on the oxidation of Cys residues.
      We demonstrate further that mutant SOD1 proteins associated with the mitochondria
      tend to form cross-linked oligomers and that their presence causes a shift in the
      redox state of these organelles and results in impairment of respiratory
      complexes. The observation that such a diverse set of mutant SOD1 proteins behave
      so similarly in mitochondria of motoneuronal cells and so differently from wild
      type SOD1 suggests that this behavior may explain the toxicity of ALS-mutant SOD1
      proteins, which causes motor neurons to die.

PMID- 16945902
TI  - Rats produced by interspecies spermatogonial transplantation in mice and in vitro
      microinsemination.
AB  - Spermatogonial transplantation has demonstrated a unique opportunity for studying
      spermatogenesis and provided an assay for spermatogonial stem cells. However, it
      has remained unknown whether germ cells that matured in a xenogeneic environment
      are functionally normal. In this investigation, we demonstrate the successful
      production of xenogeneic offspring by using spermatogonial transplantation. Rat
      spermatogonial stem cells were collected from immature testis and transplanted
      into the seminiferous tubules of busulfan-treated nude mouse testis. Using rat
      spermatids or spermatozoa that developed in xenogeneic surrogate mice, rat
      offspring were born from fresh and cryopreserved donor cells after
      microinsemination with rat oocytes. These offspring were fertile and had a normal
      imprinting pattern. The xenogeneic offspring production by interspecies germ cell
      transplantation and in vitro microinsemination will become a powerful tool in
      animal transgenesis and species conservation.

PMID- 16945903
TI  - DNA-mediated anisotropic mechanical reinforcement of a virus.
AB  - In this work, we provide evidence of a mechanism to reinforce the strength of an
      icosahedral virus by using its genomic DNA as a structural element. The
      mechanical properties of individual empty capsids and DNA-containing virions of
      the minute virus of mice are investigated by using atomic force microscopy. The
      stiffness of the empty capsid is found to be isotropic. Remarkably, the presence
      of the DNA inside the virion leads to an anisotropic reinforcement of the virus
      stiffness by approximately 3%, 40%, and 140% along the fivefold, threefold, and
      twofold symmetry axes, respectively. A finite element model of the virus
      indicates that this anisotropic mechanical reinforcement is due to DNA stretches
      bound to 60 concavities of the capsid. These results, together with evidence of
      biologically relevant conformational rearrangements of the capsid around pores
      located at the fivefold symmetry axes, suggest that the bound DNA may reinforce
      the overall stiffness of the viral particle without canceling the conformational
      changes needed for its infectivity.

PMID- 16945904
TI  - Climatically driven emissions of hydrocarbons from marine sediments during
      deglaciation.
AB  - Marine hydrocarbon seepage emits oil and gas, including methane ( approximately
      30 Tg of CH(4) per year), to the ocean and atmosphere. Sediments from the
      California margin contain preserved tar, primarily formed through hydrocarbon
      weathering at the sea surface. We present a record of variation in the abundance
      of tar in sediments for the past 32,000 years, providing evidence for increases
      in hydrocarbon emissions before and during Termination IA [16,000 years ago (16
      ka) to 14 ka] and again over Termination IB (11-10 ka). Our study provides direct
      evidence for increased hydrocarbon seepage associated with deglacial warming
      through tar abundance in marine sediments, independent of previous geochemical
      proxies. Climate-sensitive gas hydrates may modulate thermogenic hydrocarbon
      seepage during deglaciation.

PMID- 16945905
TI  - NikR-operator complex structure and the mechanism of repressor activation by
      metal ions.
AB  - Metal ion homeostasis is critical to the survival of all cells. Regulation of
      nickel concentrations in Escherichia coli is mediated by the NikR repressor via
      nickel-induced transcriptional repression of the nickel ABC-type transporter,
      NikABCDE. Here, we report two crystal structures of nickel-activated E. coli
      NikR, the isolated repressor at 2.1 A resolution and in a complex with its
      operator DNA sequence from the nik promoter at 3.1 A resolution. Along with the
      previously published structure of apo-NikR, these structures allow us to evaluate
      functional proposals for how metal ions activate NikR, delineate the drastic
      conformational changes required for operator recognition, and describe the
      formation of a second metal-binding site in the presence of DNA. They also
      provide a rare set of structural views of a ligand-responsive transcription
      factor in the unbound, ligand-induced, and DNA-bound states, establishing a model
      system for the study of ligand-mediated effects on transcription factor function.

PMID- 16945907
TI  - Structure of an RNA switch that enforces stringent retroviral genomic RNA
      dimerization.
AB  - Retroviruses selectively package two copies of their RNA genomes in the context
      of a large excess of nongenomic RNA. Specific packaging of genomic RNA is
      achieved, in part, by recognizing RNAs that form a poorly understood dimeric
      structure at their 5' ends. We identify, quantify the stability of, and use
      extensive experimental constraints to calculate a 3D model for a tertiary
      structure domain that mediates specific interactions between RNA genomes in a
      gamma retrovirus. In an initial interaction, two stem-loop structures from one
      RNA form highly stringent cross-strand loop-loop base pairs with the same
      structures on a second genomic RNA. Upon subsequent folding to the final dimer
      state, these intergenomic RNA interactions convert to a high affinity and compact
      tertiary structure, stabilized by interdigitated interactions between U-shaped
      RNA units. This retroviral conformational switch model illustrates how two-step
      formation of an RNA tertiary structure yields a stringent molecular recognition
      event at early assembly steps that can be converted to the stable RNA
      architecture likely packaged into nascent virions.

PMID- 16945906
TI  - A single lentiviral vector platform for microRNA-based conditional RNA
      interference and coordinated transgene expression.
AB  - RNAi is proving to be a powerful experimental tool for the functional annotation
      of mammalian genomes. The full potential of this technology will be realized
      through development of approaches permitting regulated manipulation of endogenous
      gene expression with coordinated reexpression of exogenous transgenes. We
      describe the development of a lentiviral vector platform, pSLIK (single
      lentivector for inducible knockdown), which permits tetracycline-regulated
      expression of microRNA-like short hairpin RNAs from a single viral infection of
      any naive cell system. In mouse embryonic fibroblasts, the pSLIK platform was
      used to conditionally deplete the expression of the heterotrimeric G proteins
      Galpha12 and Galpha13 both singly and in combination, demonstrating the Galpha13
      dependence of serum response element-mediated transcription. In RAW264.7
      macrophages, regulated knockdown of Gbeta2 correlated with a reduced Ca(2+)
      response to C5a. Insertion of a GFP transgene upstream of the Gbeta2 microRNA
      like short hairpin RNA allowed concomitant reexpression of a heterologous mRNA
      during tetracycline-dependent target gene knockdown, significantly enhancing the
      experimental applicability of the pSLIK system.

PMID- 16945908
TI  - Purification and molecular cloning of a DNA ADP-ribosylating protein, CARP-1,
      from the edible clam Meretrix lamarckii.
AB  - The cabbage butterflies Pieris rapae and Pieris brassicae have unique enzymes,
      named pierisin-1 and -2, respectively, that catalyze the ADP-ribosylation of
      guanine residues of DNA, which has been linked with induction of apoptosis and
      mutation in mammalian cell lines. In the present study, we identified ADP
      ribosylation activity targeting DNA in six kinds of edible clam. Similar to our
      observations with pierisin-1 and -2, crude extracts from the clams Meretrix
      lamarckii, Ruditapes philippinarum, and Corbicula japonica incubated with calf
      thymus DNA and beta-NAD resulted in production of N(2)-(ADP-ribos-1-yl)-2'
      deoxyguanosine. The DNA ADP-ribosylating protein in the hard clam M. lamarckii,
      designated as CARP-1, was purified by column chromatography, and its cDNA was
      cloned. The cDNA encodes a 182-aa protein with a calculated molecular mass of
      20,332. The protein synthesized in vitro from the cDNA in a reticulocyte lysate
      exhibited the same ADP-ribosylating activity as that of purified CARP-1. Neither
      the nucleotide nor the deduced amino acid sequence of CARP-1 showed homology with
      pierisin-1 or -2. However, a glutamic acid residue (E128) at the putative NAD
      binding site, conserved in all ADP-ribosyltransferases, was found in CARP-1, and
      replacement of aspartic acid for this glutamic acid resulted in loss of almost
      all ADP-ribosylating activity. CARP-1 in the culture medium showed no
      cytotoxicity against HeLa and TMK-1 cells; however, introduction of this protein
      by electroporation induced apoptosis in these cells. The finding of clam ADP
      ribosylating protein targeting guanine residues in DNA could offer new insights
      into the biological significance of ADP-ribosylation of DNA.

PMID- 16945909
TI  - The iminosugar isofagomine increases the activity of N370S mutant acid beta
      glucosidase in Gaucher fibroblasts by several mechanisms.
AB  - Gaucher disease is a lysosomal storage disorder caused by deficiency in lysosomal
      acid beta-glucosidase (GlcCerase), the enzyme responsible for the catabolism of
      glucosylceramide. One of the most prevalent disease-causing mutations, N370S,
      results in an enzyme with lower catalytic activity and impaired exit from the
      endoplasmic reticulum. Here, we report that the iminosugar isofagomine (IFG), an
      active-site inhibitor, increases GlcCerase activity 3.0 +/- 0.6-fold in N370S
      fibroblasts by several mechanisms. A major effect of IFG is to facilitate the
      folding and transport of newly synthesized GlcCerase in the endoplasmic
      reticulum, thereby increasing the lysosomal pool of the enzyme. In addition,
      N370S GlcCerase synthesized in the presence of IFG exhibits a shift in pH optimum
      from 6.4 to 5.2 and altered sensitivity to SDS. Although IFG fully inhibits
      GlcCerase in the lysosome in an in situ assay, washout of the drug leads to
      partial recovery of GlcCerase activity within 4 h and full recovery by 24 h.
      These findings provide support for the possible use of active-site inhibitors in
      the treatment of some forms of Gaucher disease.

PMID- 16945910
TI  - Admixture mapping identifies 8q24 as a prostate cancer risk locus in African
      American men.
AB  - A whole-genome admixture scan in 1,597 African Americans identified a 3.8 Mb
      interval on chromosome 8q24 as significantly associated with susceptibility to
      prostate cancer [logarithm of odds (LOD) = 7.1]. The increased risk because of
      inheriting African ancestry is greater in men diagnosed before 72 years of age (P
      < 0.00032) and may contribute to the epidemiological observation that the higher
      risk for prostate cancer in African Americans is greatest in younger men (and
      attenuates with older age). The same region was recently identified through
      linkage analysis of prostate cancer, followed by fine-mapping. We strongly
      replicated this association (P < 4.2 x 10(-9)) but find that the previously
      described alleles do not explain more than a fraction of the admixture signal.
      Thus, admixture mapping indicates a major, still-unidentified risk gene for
      prostate cancer at 8q24, motivating intense work to find it.

PMID- 16945911
TI  - Parallel genetic origins of pelvic reduction in vertebrates.
AB  - Despite longstanding interest in parallel evolution, little is known about the
      genes that control similar traits in different lineages of vertebrates. Pelvic
      reduction in stickleback fish (family Gasterosteidae) provides a striking example
      of parallel evolution in a genetically tractable system. Previous studies suggest
      that cis-acting regulatory changes at the Pitx1 locus control pelvic reduction in
      a population of threespine sticklebacks (Gasterosteus aculeatus). In this study,
      progeny from intergeneric crosses between pelvic-reduced threespine and ninespine
      (Pungitius pungitius) sticklebacks also showed severe pelvic reduction,
      implicating a similar genetic origin for this trait in both genera. Comparative
      sequencing studies in complete and pelvic-reduced Pungitius revealed no
      differences in the Pitx1 coding sequences, but Pitx1 expression was absent from
      the prospective pelvic region of larvae from pelvic-reduced parents. A much more
      phylogenetically distant example of pelvic reduction, loss of hindlimbs in
      manatees, shows a similar left-right size bias that is a morphological signature
      of Pitx1-mediated pelvic reduction in both sticklebacks and mice. These multiple
      lines of evidence suggest that changes in Pitx1 may represent a key mechanism of
      morphological evolution in multiple populations, species, and genera of
      sticklebacks, as well as in distantly related vertebrate lineages.

PMID- 16945912
TI  - Hmgb3 regulates the balance between hematopoietic stem cell self-renewal and
      differentiation.
AB  - Hmgb3 is an X-linked member of a family of sequence-independent chromatin-binding
      proteins that is preferentially expressed in hematopoietic stem cells (HSC).
      Hmgb3-deficient mice (Hmgb3(-/Y)) contain normal numbers of HSCs, capable of self
      renewal and hematopoietic repopulation, but fewer common lymphoid (CLP) and
      common myeloid progenitors (CMP). In this study, we tested the hypothesis that
      Hmgb3(-/Y) HSCs are biased toward self-renewal at the expense of progenitor
      production. Wild-type and Hmgb3(-/Y) CLPs and CMPs proliferate and differentiate
      equally in vitro, indicating that CLP and CMP function normally in Hmgb3(-/Y)
      mice. Hmgb3(-/Y) HSCs exhibit constitutive activation of the canonical Wnt
      signaling pathway, which regulates stem cell self-renewal. Increased Wnt
      signaling in Hmgb3(-/Y) HSCs corresponds to increased expression of Dvl1, a
      positive regulator of the canonical Wnt pathway. To induce hematopoietic stress
      and a subsequent response from HSCs, we treated Hmgb3(-/Y) mice with 5
      fluorouracil. Hmgb3(-/Y) mice exhibit a faster recovery of functional HSCs after
      administration of 5-fluorouracil compared with wild-type mice, which may be due
      to the increased Wnt signaling. Furthermore, the recovery of HSC number in Hmgb3(
      /Y) mice occurs more rapidly than CLP and CMP recovery. From these data, we
      propose a model in which Hmgb3 is required for the proper balance between HSC
      self-renewal and differentiation.

PMID- 16945913
TI  - Biosynthesis of mycobacterial lipoarabinomannan: role of a branching
      mannosyltransferase.
AB  - Lipoarabinomannan (LAM), one of the few known bacterial glycosylphosphoinositides
      (GPIs), occurs in various structural forms in Mycobacterium species. It has been
      implicated in key aspects of the physiology of Mycobacterium tuberculosis and the
      immunology and pathogenesis of tuberculosis. Yet, little is known of the
      biosynthesis of LAM. A bioinformatics approach identified putative integral
      membrane proteins, MSMEG4250 in Mycobacterium smegmatis and Rv2181 in M.
      tuberculosis, with 10 predicted transmembrane domains and a glycosyltransferase
      (GT) motif (DID), features that are common to eukaryotic mannosyltransferases
      (ManTs) of the GT-C superfamily that rely on polyprenyl-linked rather than
      nucleotide-linked sugar donors. Inactivation of M. smegmatis MSMEG4250 by allelic
      exchange resulted in altered growth and inability to synthesize lipomannan (LM)
      but accumulation of a previously uncharacterized, truncated LAM. MALDI-TOF/MS and
      NMR indicated a structure lower in molecular weight than the native molecule, a
      preponderance of 6-linked Manp residues, and the absence of 2,6-linked and
      terminal Manp. Complementation of the mutant with the corresponding ortholog of
      M. tuberculosis H37Rv restored normal LM/LAM synthesis. The data suggest that
      MSMEG4250 and Rv2181 are ManTs that are responsible for the addition of alpha(1-
      >2) branches to the mannan core of LM/LAM and that arrest of this branching in
      the mutant deters formation of native LAM. The results allow for the presentation
      of a unique model of LM and LAM biosynthesis. The generation of mutants defective
      in the synthesis of LM/LAM will help define the role of these GPIs in the
      immunology and pathogenesis of mycobacterial infections and physiology of the
      organism.

PMID- 16945914
TI  - Nonimmune immunoglobulin binding and multiple adhesion characterize Plasmodium
      falciparum-infected erythrocytes of placental origin.
AB  - The harmful effects of pregnancy-associated malaria (PAM) are engendered by the
      heavy sequestration of Plasmodium falciparum-parasitized RBCs in the placenta. It
      is well documented that this process is mediated by interactions of parasite
      encoded variant surface antigens and placental receptors. A P. falciparum
      erythrocyte membrane protein 1 variant, VAR2CSA, and the placental receptor
      chondroitin sulfate A (CSA) are currently the focus of PAM research. A role for
      immunoglobulins (IgG and IgM) from normal human serum and hyaluronic acid as
      additional receptors in placental sequestration have also been suggested. We show
      here (i) that CSA and nonimmune IgG/IgM binding are linked phenotypes of in vitro
      adapted parasites, (ii) that a VAR2CSA variant shown to bind CSA also harbors IgG
      and IgM-binding domains (DBL2-X, DBL5-epsilon, and DBL6-epsilon), and (iii) that
      IgG and IgM binding and adhesion to multiple receptors (IgG/IgM/HA/CSA) rather
      than the exclusive binding to CSA is a characteristic of fresh Ugandan placental
      isolates. These findings are of importance for the understanding of the
      pathogenesis of placental malaria and have implications for the ongoing efforts
      to develop a global PAM vaccine.

PMID- 16945915
TI  - Consistent resting-state networks across healthy subjects.
AB  - Functional MRI (fMRI) can be applied to study the functional connectivity of the
      human brain. It has been suggested that fluctuations in the blood oxygenation
      level-dependent (BOLD) signal during rest reflect the neuronal baseline activity
      of the brain, representing the state of the human brain in the absence of goal
      directed neuronal action and external input, and that these slow fluctuations
      correspond to functionally relevant resting-state networks. Several studies on
      resting fMRI have been conducted, reporting an apparent similarity between the
      identified patterns. The spatial consistency of these resting patterns, however,
      has not yet been evaluated and quantified. In this study, we apply a data
      analysis approach called tensor probabilistic independent component analysis to
      resting-state fMRI data to find coherencies that are consistent across subjects
      and sessions. We characterize and quantify the consistency of these effects by
      using a bootstrapping approach, and we estimate the BOLD amplitude modulation as
      well as the voxel-wise cross-subject variation. The analysis found 10 patterns
      with potential functional relevance, consisting of regions known to be involved
      in motor function, visual processing, executive functioning, auditory processing,
      memory, and the so-called default-mode network, each with BOLD signal changes up
      to 3%. In general, areas with a high mean percentage BOLD signal are consistent
      and show the least variation around the mean. These findings show that the
      baseline activity of the brain is consistent across subjects exhibiting
      significant temporal dynamics, with percentage BOLD signal change comparable with
      the signal changes found in task-related experiments.

PMID- 16945916
TI  - Leishmania disease development depends on the presence of apoptotic promastigotes
      in the virulent inoculum.
AB  - The obligate intracellular pathogen Leishmania major survives and multiplies in
      professional phagocytes. The evasion strategy to circumvent killing by host
      phagocytes and establish a productive infection is poorly understood. Here we
      report that the virulent inoculum of Leishmania promastigotes contains a high
      ratio of annexin A5-binding apoptotic parasites. This subpopulation of parasites
      is characterized by a round body shape, a swollen kinetoplast, nuclear
      condensation, and a lack of multiplication and represents dying or already dead
      parasites. After depleting the apoptotic parasites from a virulent population,
      Leishmania do not survive in phagocytes in vitro and lose their disease-inducing
      ability in vivo. TGF-beta induced by apoptotic parasites is likely to mediate the
      silencing of phagocytes and lead to survival of infectious Leishmania
      populations. The data demonstrate that apoptotic promastigotes, in an altruistic
      way, enable the intracellular survival of the viable parasites.

PMID- 16945917
TI  - Inhibition of a spliceosome turnover pathway suppresses splicing defects.
AB  - Defects in assembly are suggested to signal the dissociation of faulty splicing
      complexes. A yeast genetic screen was performed to identify components of the
      putative discard pathway. Weak mutant alleles of SPP382 (also called NTR1) were
      found to suppress defects in two proteins required for spliceosome activation,
      Prp38p and Prp8p. Spp382p is shown necessary for cellular splicing, with premRNA
      and, for some alleles, excised intron, accumulating after inactivation. Like
      spp382-1, a mutant allele of AAR2 was identified in this suppressor screen. Like
      Spp382p, Aar2p has a reported role in spliceosome recycling and is found with
      Spp382p in a complex recovered with a mutant version of the spliceosomal core
      protein Prp8p. Possible insight into to the spp382 suppressor phenotype is
      provided by the observation that defective splicing complexes lacking the 5' exon
      cleavage intermediate are recovered by a tandem affinity purification-tagged
      Spp382 derivative. Stringent proteomic and two-hybrid analyses show that Spp382p
      also interacts with Cwc23p, a DNA J-like protein present in the spliceosome and
      copurified with the Prp43p DExD/H-box ATPase. Spp382p binds Prp43p and Prp43p
      requires Spp382p for intron release from the spliceosome. Consistent with a
      related function in the removal of defective complexes, three prp43 mutants are
      also shown to suppress splicing defects, with efficiencies inversely
      proportionate to the measured ATPase activities. These and related genetic data
      support the existence of a Spp382p-dependent turnover pathway acting on defective
      spliceosomes.

PMID- 16945918
TI  - The marine product cephalostatin 1 activates an endoplasmic reticulum stress
      specific and apoptosome-independent apoptotic signaling pathway.
AB  - Cephalostatin 1, a bis-steroidal marine natural product, has been reported to
      induce apoptosis without the requirement of an active caspase-8 or mitochondrial
      cytochrome c release and apoptosome formation. Here we show that despite the
      absence of these events, caspase-9 activation is essential for cephalostatin 1
      induced apoptosis. Cephalostatin 1 initiates a rapid endoplasmic reticulum stress
      response characterized by phosphorylation of eukaryotic initiation factor-2 alpha
      subunit and increased expression of the chaperone immunoglobulin heavy chain
      binding protein GRP78 as well as the transcription factor C/EBP homologous
      protein (CHOP)/GADD153. Cephalostatin 1 activates apoptosis signal-regulating
      kinase 1 and c-Jun N-terminal kinase (JNK). However, this pathway does not play a
      major role in cephalostatin 1-induced apoptosis, as assessed by stable expression
      of a dominant negative apoptosis signal-regulating kinase 1. Importantly, the
      endoplasmic reticulum-associated caspase-4 is required and as shown by
      biochemical and genetic inhibition experiments, acts upstream of caspase-9 in
      cephalostatin-induced apoptosis.

PMID- 16945919
TI  - Thioredoxin-h1 reduces and reactivates the oxidized cytosolic malate
      dehydrogenase dimer in higher plants.
AB  - Cytosolic malate dehydrogenase (cytMDH) was captured by thioredoxin affinity
      chromatography as a possible target protein of cytosolic thioredoxin (Yamazaki,
      D., Motohashi, K., Kasama, T., Hara, Y., and Hisabori, T. (2004) Plant Cell
      Physiol. 45, 18-27). To further dissect this interaction, we aimed to determine
      whether cytMDH can interact with the cytosolic thioredoxin and whether its
      activity is redox-regulated. We obtained the active recombinant cytMDH that could
      be oxidized and rendered inactive. Inactivation was reversed by incubation with
      low concentrations of dithiothreitol in the presence of recombinant Arabidopsis
      thaliana thioredoxin-h1. Inactivation of cytMDH was found to result from
      formation of a homodimer. By cysteine mutant analysis and peptide mapping
      analysis, we were able to determine that the cytMDH homodimer occurs by formation
      of a disulfide bond via the Cys(330) residue. Moreover, we found this bond to be
      efficiently reduced by the reduced form of thioredoxin-h1. These results
      demonstrate that the oxidized form cytMDH dimer is a preferable target protein of
      the reduced form thioredoxin-h1 as suggested by thioredoxin affinity
      chromatography.

PMID- 16945920
TI  - Structure of the calmodulin alphaII-spectrin complex provides insight into the
      regulation of cell plasticity.
AB  - AlphaII-spectrin is a major cortical cytoskeletal protein contributing to
      membrane organization and integrity. The Ca2+-activated binding of calmodulin to
      an unstructured insert in the 11th repeat unit of alphaII-spectrin enhances the
      susceptibility of spectrin to calpain cleavage but abolishes its sensitivity to
      several caspases and to at least one bacterially derived pathologic protease.
      Other regulatory inputs including phosphorylation by c-Src also modulate the
      proteolytic susceptibility of alphaII-spectrin. These pathways, acting through
      spectrin, appear to control membrane plasticity and integrity in several cell
      types. To provide a structural basis for understanding these crucial biological
      events, we have solved the crystal structure of a complex between bovine
      calmodulin and the calmodulin-binding domain of human alphaII-spectrin (Protein
      Data Bank ID code 2FOT). The structure revealed that the entire calmodulin
      spectrin-binding interface is hydrophobic in nature. The spectrin domain is also
      unique in folding into an amphiphilic helix once positioned within the calmodulin
      binding groove. The structure of this complex provides insight into the
      mechanisms by which calmodulin, calpain, caspase, and tyrosine phosphorylation
      act on spectrin to regulate essential cellular processes.

PMID- 16945921
TI  - Sgt1p is a unique co-chaperone that acts as a client adaptor to link Hsp90 to
      Skp1p.
AB  - Sgt1p is a conserved, essential protein required for kinetochore assembly in both
      yeast and animal cells. Sgt1p has homology to both TPR and p23 domains, sequences
      often found in proteins that interact with and regulate the molecular chaperone,
      Hsp90. The presence of these domains and the recent findings that Sgt1p interacts
      with Hsp90 has led to the speculation that Sgt1p and Hsp90 form a co-chaperone
      complex. To test this possibility, we have used purified recombinant proteins to
      characterize the in vitro interactions between yeast Sgt1p and Hsp82p (an Hsp90
      homologue in yeast). We show that Sgt1p interacts directly with Hsp82p via its
      p23 homology region in a nucleotide-dependent manner. However, Sgt1p binding does
      not alter the enzymatic activity of Hsp82p, suggesting that it is distinct from
      other co-chaperones. We find that Sgt1p can form a ternary chaperone complex with
      Hsp82p and Sti1p, a well characterized Hsp90 co-chaperone. Sgt1p interacts with
      its binding partner Skp1p through its TPR domains and links Skp1p to the core
      Hsp82p-Sti1p co-chaperone complex. The multidomain nature of Sgt1p and its
      ability to bridge the interaction between Skp1p and Hsp82p argue that Sgt1p acts
      as a "client adaptor" recruiting specific clients to Hsp82p co-chaperone
      complexes.

PMID- 16945922
TI  - The NR4A orphan nuclear receptor NOR1 is induced by platelet-derived growth
      factor and mediates vascular smooth muscle cell proliferation.
AB  - Members of the nuclear hormone receptor superfamily function as key
      transcriptional regulators of inflammation and proliferation in cardiovascular
      diseases. In addition to the ligand-dependent peroxisome proliferator-activated
      receptors and liver X receptors, this family of transcription factors includes a
      large number of orphan receptors, and their role in vascular diseases remains to
      be investigated. The neuron-derived orphan receptor-1 (NOR1) belongs to the
      ligand-independent NR4A subfamily, which has been implicated in cell
      proliferation, differentiation, and apoptosis. In this study, we demonstrate NOR1
      expression in vascular smooth muscle cells (SMC) of human atherosclerotic
      lesions. In response to mitogenic stimulation with platelet-derived growth factor
      (PDGF), SMC rapidly express NOR1 through an ERK-MAPK-dependent signaling pathway.
      5'-deletion analysis, site-directed mutagenesis, and transactivation experiments
      demonstrate that PDGF-induced NOR1 expression is mediated through a cAMP-response
      element-binding protein (CREB)-dependent transactivation of the NOR1 promoter.
      Consequently, short interfering RNA-mediated depletion of CREB abolished PDGF
      induced NOR1 expression in SMC. Furthermore, PDGF induced Ser-133 phosphorylation
      of CREB and subsequent binding to the CRE sites of the endogenous NOR1 promoter.
      Functional analysis demonstrated that PDGF induces NOR1 transactivation of its
      consensus NGFI-B-response elements (NBRE) in SMC. We finally demonstrate that SMC
      isolated from NOR1-deficient mice exhibit decreased cell proliferation and
      characterize cyclin D1 and D2 as NOR1 target genes in SMC. These experiments
      indicate that PDGF-induced NOR1 transcription in SMC is mediated through CREB
      dependent transactivation of the NOR1 promoter and further demonstrate that NOR1
      functions as a key transcriptional regulator of SMC proliferation.

PMID- 16945923
TI  - Ubiquilin 1 modulates amyloid precursor protein trafficking and Abeta secretion.
AB  - Ubiquilin 1 (UBQLN1) is a ubiquitin-like protein, which has been shown to play a
      central role in regulating the proteasomal degradation of various proteins,
      including the presenilins. We recently reported that DNA variants in UBQLN1
      increase the risk for Alzheimer disease, by influencing expression of this gene
      in brain. Here we present the first assessment of the effects of UBQLN1 on the
      metabolism of the amyloid precursor protein (APP). For this purpose, we employed
      RNA interference to down-regulate UBQLN1 in a variety of neuronal and non
      neuronal cell lines. We demonstrate that down-regulation of UBQLN1 accelerates
      the maturation and intracellular trafficking of APP, while not interfering with
      alpha-, beta-, or gamma-secretase levels or activity. UBQLN1 knockdown increased
      the ratio of APP mature/immature, increased levels of full-length APP on the cell
      surface, and enhanced the secretion of sAPP (alpha- and beta-forms). Moreover,
      UBQLN1 knockdown increased levels of secreted Abeta40 and Abeta42. Finally,
      employing a fluorescence resonance energy transfer-based assay, we show that
      UBQLN1 and APP come into close proximity in intact cells, independently of the
      presence of the presenilins. Collectively, our findings suggest that UBQLN1 may
      normally serve as a cytoplasmic "gatekeeper" that may control APP trafficking
      from intracellular compartments to the cell surface. These findings suggest that
      changes in UBQLN1 steady-state levels affect APP trafficking and processing,
      thereby influencing the generation of Abeta.

PMID- 16945924
TI  - Azumolene inhibits a component of store-operated calcium entry coupled to the
      skeletal muscle ryanodine receptor.
AB  - Dantrolene reduces the elevated myoplasmic Ca(2+) generated during malignant
      hyperthermia, a pharmacogenetic crisis triggered by volatile anesthetics.
      Although specific binding of dantrolene to the type 1 ryanodine receptor (RyR1),
      the Ca(2+) release channel of skeletal muscle sarcoplasmic reticulum, has been
      demonstrated, there is little evidence for direct dantrolene inhibition of RyR1
      channel function. Recent studies suggest store-operated Ca(2+) entry (SOCE)
      contributes to skeletal muscle function, but the effect of dantrolene on this
      pathway has not been examined. Here we show that azumolene, an equipotent
      dantrolene analog, inhibits a component of SOCE coupled to activation of RyR1 by
      caffeine and ryanodine, whereas the SOCE component induced by thapsigargin is not
      affected. Our data suggest that azumolene distinguishes between two mechanisms of
      cellular signaling to SOCE in skeletal muscle, one that is coupled to and one
      independent from RyR1.

PMID- 16945925
TI  - Heme oxygenase-1 protects gastric mucosal cells against non-steroidal anti
      inflammatory drugs.
AB  - Gastric mucosal cell death by non-steroidal anti-inflammatory drugs (NSAIDs) is
      suggested to be involved in NSAID-induced gastric lesions. Therefore, cellular
      factors that suppress this cell death are important for protection of the gastric
      mucosa from NSAIDs. Heme oxygenase-1 (HO-1) is up-regulated by various stressors
      and protects cells against stressors. Here, we have examined up-regulation of HO
      1 by NSAIDs and the contribution of HO-1 to the protection of gastric mucosal
      cells against NSAIDs both in vitro and in vivo. In cultured gastric mucosal
      cells, all NSAIDs tested up-regulated HO-1. In rats, orally administered
      indomethacin up-regulated HO-1, induced apoptosis, and produced lesions at
      gastric mucosa. An inhibitor of HO-stimulated NSAID-induced apoptosis in vitro
      and in vivo and also stimulated NSAID-produced gastric lesions, suggesting that
      NSAID-induced up-regulation of HO-1 protects the gastric mucosa from NSAID
      induced gastric lesions by inhibiting NSAID-induced apoptosis. Indomethacin
      activated the HO-1 promoter and caused nuclear accumulation of NF-E2-related
      factor 2 (Nrf2), a transcription factor for the HO-1 gene. Examination of
      phosphorylation of p38 mitogen-activated protein kinase (MAPK) and experiments
      with its inhibitor strongly suggest that the nuclear accumulation of Nrf2 and
      resulting up-regulation of HO-1 by NSAIDs is mediated through NSAID-dependent
      activation (phosphorylation) of p38 MAPK. This is the first report showing the
      protective role of HO-1 against irritant-induced gastric lesions.

PMID- 16945926
TI  - Interaction of neurochondrin with the melanin-concentrating hormone receptor 1
      interferes with G protein-coupled signal transduction but not agonist-mediated
      internalization.
AB  - Screening of a human brain cDNA library using the C-terminal tail of the melanin
      concentrating hormone receptor 1 (MCHR1) as bait in a yeast two-hybrid assay
      resulted in the identification of the neurite-outgrowth related factor,
      neurochondrin. This interaction was verified in overlay, pulldown, and co
      immunoprecipitation assays. Deletion mapping confined the binding to the C
      terminus of neurochondrin and to the proximal C terminus of MCHR1, a region known
      to be involved in G protein binding and signal transduction. This region of the
      MCHR1 is also able to interact with the actin- and intermediate filament-binding
      protein, periplakin. Interactions of MCHR1 with neurochondrin and periplakin were
      competitive, indicating that these two proteins bind to overlapping regions of
      MCHR1. Although neurochondrin did not interfere with melanin-concentrating
      hormone-mediated internalization of the receptor, it did inhibit G protein
      coupled signal transduction via both Galpha(i/o) and Galpha(q/11) family G
      proteins as measured by each of melanin-concentrating hormone-induced G protein
      activated inwardly rectifying K(+) channel activity of voltage-clamped amphibian
      oocytes, by calcium mobilization in transfected mammalian cells, and by reduction
      in the capacity of melanin-concentrating hormone to promote binding of
      [(35)S]guanosine 5'-3-O-(thio)triphosphate to both Galpha(o1) and Galpha(11).
      Immunohistochemistry revealed co-expression of neurochondrin and MCHR1 within the
      rodent brain, suggesting that neurochondrin may be involved in the regulation of
      MCHR1 signaling and play a role in modulating melanin-concentrating hormone
      mediated functions in vivo.

PMID- 16945927
TI  - A specific dileucine motif is required for the GGA-dependent entry of newly
      synthesized insulin-responsive aminopeptidase into the insulin-responsive
      compartment.
AB  - In muscle and adipose cells, the insulin-responsive aminopeptidase (IRAP) is
      localized to intracellular storage sites and undergoes insulin-dependent
      redistribution to the cell surface. Following expression, the newly synthesized
      IRAP protein traffics to the perinuclear insulin-sensitive compartment and
      acquires insulin sensitivity 6-9 h following biosynthesis. Knockdown of GGA1 by
      RNA interference prevented IRAP from entering, but not exiting, the insulin
      responsive compartment. Mutation of the dileucine motif at positions 76 and 77
      (EGFP-IRAP/AA(76,77)), but not the dileucine motif at positions 53 and 54,
      resulted in the rapid default of the reporter to the cell surface beginning at 3
      h following biosynthesis. Alanine substitution of 9 residues amino- or carboxyl
      terminal to LL(76,77) did not perturb basal intracellular sequestration or
      abrogate insulin-stimulated IRAP translocation. Moreover, a dominant interfering
      GGA mutant (VHS-GAT) potently inhibited insulin-stimulated translocation of EGFP
      IRAP/WT but did not block the constitutive exocytotic trafficking of EGFP
      IRAP/AA(76,77). In addition, the EGFP-IRAP/WT and EGFP-IRAP/AA(76,77) constructs
      occupied morphologically distinct tubulovesicular compartments in the perinuclear
      region. Taken together, these data indicate that LL(76,77) functions during the
      GGA-dependent sorting of newly made IRAP into the insulin-responsive storage
      compartment.

PMID- 16945928
TI  - GATA-4 incompletely substitutes for GATA-1 in promoting both primitive and
      definitive erythropoiesis in vivo.
AB  - Vertebrate GATA transcription factors have been classified into two subgroups;
      GATA-1, GATA-2, and GATA-3 are expressed in hematopoietic cells, whereas GATA-4,
      GATA-5, and GATA-6 are expressed in mesoendoderm-derived tissues. We previously
      discovered that expression of GATA-2 or GATA-3 under the transcriptional control
      for the Gata1 gene eliminates lethal anemia in Gata1 germ line mutant mice
      (Gata1.05/Y). Here, we show that the GATA-4 expression by the same regulatory
      cassette prolongs the life span of Gata1.05/Y embryos from embryonic day 12.5 to
      15.5 but fails to abrogate its embryonic lethality. Gata1.05/Y mice bearing the
      GATA-4 transgene showed impaired maturation of both primitive and definitive
      erythroid cells and defective erythroid cell expansion in fetal liver. Moreover,
      the incidence of apoptosis was observed prominently in primitive erythroid cells.
      In contrast, a GATA-4-GATA-1 chimeric protein prepared by linking the N-terminal
      region of GATA-4 to the C-terminal region of GATA-1 significantly promoted the
      differentiation and survival of primitive erythroid cells, although this protein
      is still insufficient for rescuing Gata1.05/Y embryos from lethal anemia. These
      data thus show a functional incompatibility between hematopoietic and endodermal
      GATA factors in vivo and provide evidence indicating specific roles of the C
      terminal region of GATA-1 in primitive erythropoiesis.

PMID- 16945929
TI  - Laminin alpha1 chain LG4 module promotes cell attachment through syndecans and
      cell spreading through integrin alpha2beta1.
AB  - The laminin alpha1 chain is a subunit of laminin-1, a heterotrimeric basement
      membrane protein. The LG4-5 module at the C terminus of laminin alpha1 contains
      major binding sites for heparin, sulfatide, and alpha-dystroglycan and plays a
      critical role in early embryonic development. We previously identified active
      synthetic peptides AG73 and EF-1 from the sequence of laminin alpha1 LG4 for
      binding to syndecan and integrin alpha2beta1, respectively. However, their
      activity and functional relationship within the laminin-1 and LG4 as well as the
      functional relation between these sites and alpha-dystroglycan binding sites in
      LG4 are not clear. To address these questions, we created mutant recombinant LG4
      proteins containing alanine substitutions within the AG73 (M1), EF-1 (M2, M3),
      and alpha-dystroglycan binding sites (M4, M5) and analyzed their activities. We
      found that recombinant proteins rec-M1 and rec-M5, containing mutations within M1
      and M5, respectively, did not bind heparin or lymphoid cell lines expressing
      syndecans. These results suggest that LG4 binds to heparin and syndecans through
      M1 and M5. Rec-M1 and rec-M5 reduced fibroblast attachment, whereas mutant rec-M2
      and rec-M3 retained cell attachment activity but did not promote cell spreading.
      Fibroblast attachment to rec-LG4 was inhibited by heparin but not by integrin
      antibodies. Spreading of fibroblasts on rec-LG4 was inhibited by anti-integrin
      alpha2 and beta1 but not by anti-integrin alpha1 and alpha6. These results
      suggest that the M1 and M5 sites are necessary for cell attachment on LG4 through
      syndecans and that the EF-1 site is for cell spreading activity through integrin
      alpha2beta1. In contrast, laminin-1-mediated fibroblast attachment and spreading
      were not inhibited by heparin or anti-integrin alpha2. Our findings indicate that
      LG4 has a unique function distinct from laminin-1 and suggest that laminin alpha1
      LG4-5 may also be produced by a proteolytic cleavage in certain tissues where it
      exerts its activity.

PMID- 16945931
TI  - Volte-face on venlafaxine--reasons and reflections.

PMID- 16945930
TI  - Acylation of CD44 and its association with lipid rafts are required for receptor
      and hyaluronan endocytosis.
AB  - CD44 is a cell surface receptor for the extracellular matrix macromolecule
      hyaluronan. In addition, CD44 mediates the endocytosis of hyaluronan leading to
      its subsequent degradation within lysosomes. Using model systems of COS-7 and Flp
      293 cells, we demonstrate that the association of CD44 with lipid rafts is
      essential for the endocytosis of hyaluronan but not the extracellular binding.
      Further, we demonstrate that palmitoylation of CD44 on two highly conserved
      cysteine residues is essential for the association with lipid rafts as determined
      by density gradient ultracentrifugation. Mutations of either cysteine residues or
      pretreatment of cells with the palmitic acid analog 2-bromopalmitate, reduced the
      [3H]palmitic acid incorporation into CD44 and prevented CD44-lipid rafts
      association. Preventing CD44 palmitoylation had no effect on the binding of
      hyaluronan but inhibited hyaluronan internalization. The turnover of the CD44
      receptor itself was also affected by blocking its association with lipid rafts.
      Using cycloheximide to prevent de novo protein synthesis, palmitoylation
      deficient cysteine mutants underwent slower turnover from cell surface compared
      with the palmitoylation-intact wild type, as determined by immunofluorescence and
      Western blotting. These results indicate that palmitoylation of CD44 is a
      critical driving determinant to CD44 association with lipid rafts and,
      concomitantly, the rates of hyaluronan endocytosis and CD44 turnover from cell
      surface.

PMID- 16945932
TI  - The Arabidopsis mutant stg1 identifies a function for TBP-associated factor 10 in
      plant osmotic stress adaptation.
AB  - Plant salt tolerance is a complex trait involving many genes. To identify new
      salt tolerance determinants during seed germination, we have screened a
      population of chemically inducible activation-tagged Arabidopsis mutants. A
      mutant, designated stg1 (salt tolerance during germination 1), was obtained. The
      stg1 mutant is less sensitive than the wild type to NaCl and osmotic stress
      inhibition of germination in the presence of the inducer. Germination assays on
      media containing various salts upon inducer application indicate that the stg1
      mutation enhances tolerance to Na(+) and K(+). Under salt stress, stg1 maintains
      a higher K(+)/Na(+) ratio and accumulates less proline than the wild-type
      control, suggesting that its salt tolerance mechanisms are mainly involved in the
      regulation of ion balance. STG1 encodes a putative Arabidopsis TATA box-binding
      protein (TBP)-associated factor 10 (atTAF10), which constitutes the
      transcriptional factor IID (TFIID) complex. Overexpression of atTAF10 under the
      control of the 35S promoter in Arabidopsis improves seed tolerance to salt stress
      during germination and the knocked-down mutant is more sensitive to salt stress,
      indicating the transcription initiation factor as a physiological target of salt
      toxicity in plants.

PMID- 16945933
TI  - Government reform of the National Health Service: implications for radiologists
      and diagnostic services.
AB  - Demand for radiology services within the National Health Service (NHS) continues
      unabated and current NHS operations cannot keep up with demand. Therefore, to
      meet this demand, the government has decided to outsource a significant number of
      investigations to the independent sector and will actively promote patient
      referrals to the new government sponsored Treatment Centres as they become
      available. This presents opportunities to patients, but threatens existing public
      sector providers (including doctors) as competition for radiology services may
      result in both loss of patient referrals and revenue to these providers. This
      article is a personal opinion and will focus on the current challenges facing the
      provision of radiology services in the NHS. I will suggest the possible negative
      outcomes for providers (NHS hospitals and staff alike) and will offer strategies,
      tactics and tools that can be employed to counter the threat to their existing
      services.

PMID- 16945934
TI  - Are targeted contrast agents realistically going to reach the clinic? Recent
      regulatory experience with targeted MRI contrast agents.

PMID- 16945935
TI  - On the possible increase in local tumour control probability for gliomas
      exhibiting low dose hyper-radiosensitivity using a pulsed schedule.
AB  - Using modelling, we have developed a treatment strategy for gliomas exhibiting
      low dose hyper-radiosensitivity (HRS) that employs both a reduced dose-rate and
      pulsed treatment dose delivery. The model exploits the low dose hypersensitivity
      observed in some glioma cell lines at low radiation doses. We show, based on in
      vitro data, that a pulsed delivery of external beam radiation therapy could yield
      significant increases in local control. We therefore propose a pulsed delivery
      scheme for the treatment of gliomas in which the daily treatment fraction is
      delivered using 0.20 Gy pulses, separated by three minutes for a time-averaged
      dose-rate of 0.0667 Gy/min. The dose per pulse of 0.2 Gy is near or below the
      transition dose observed in vitro for four of the five glioma cell lines we have
      studied. Using five established glioma cell lines our modelling demonstrates that
      our pulsed delivery scheme yields a substantial increase in tumour control
      probability (TCP).

PMID- 16945936
TI  - Diverse molecular mechanisms involved in AChR deficiency due to rapsyn mutations.
AB  - Congenital myasthenic syndromes are inherited disorders of neuromuscular
      transmission characterized by fatigable muscle weakness. Autosomal recessive
      acetylcholine receptor (AChR) deficiency syndromes, in which levels of this
      receptor at the neuromuscular junction are severely reduced, may be caused by
      mutations within genes encoding the AChR or the AChR-clustering protein, rapsyn.
      Most patients have mutations within the rapsyn coding region and are either
      homozygous for N88K or heteroallelic for N88K and a second mutation. In some
      cases the second allele carries a null mutation but in many the mutations are
      missense, and are located in different functional domains. Little is known about
      the functional effects of these mutations, but we hypothesize that they would
      have an effect on AChR clustering by a variety of mechanisms that might correlate
      with disease severity. Here we expressed RAPSN mutations A25V, N88K, R91L, L361R
      and K373del in TE671 cells and in rapsyn-/- myotubes to determine their
      pathogenic mechanisms. The A25Vmutation impaired colocalization of rapsyn with
      AChR and prevented agrin-induced AChR clusters in rapsyn-/- myotubes. In TE671
      cells, R91L reduced the ability of rapsyn to self-associate, and K373del-rapsyn
      was significantly less stable than wild-type. The effects of mutations L361R and
      N88K were more subtle: in TE671 cells, in comparison with wild-type rapsyn, L361R
      rapsyn showed reduced expression/stability, and both N88K-rapsyn and L361R-rapsyn
      showed significantly reduced co-localization with AChR. N88K-rapsyn and L361R
      rapsyn could effectively mediate agrin-induced AChR clusters, but these were
      reduced in number and were less stable than with wild-type rapsyn. The disease
      severity of patients harbouring the compound allelic mutations was greater than
      that of patients with homozygous rapsyn mutation N88K, suggesting that the second
      mutant allele may largely determine severity.

PMID- 16945937
TI  - Stimulation effect of Dnmt3L on the DNA methylation activity of Dnmt3a2.
AB  - Quantification of DNA methyltransferases Dnmt3a and Dnmt3a2, and Dnmt3L in
      isolated male gonocytes in day 16.5 embryos confirmed that not Dnmt3a but Dnmt3a2
      and Dnmt3L were the major Dnmt3s. The expression level of Dnmt3L constituted 5-
      to 10-fold molar excess compared to that of Dnmt3a2. The stimulation property of
      the DNA methylation activity of Dnmt3a2 with Dnmt3L towards substrate DNA in
      naked or nucleosomes was similar to that of Dnmt3a. However, the DNA methylation
      activity of not Dnmt3a but Dnmt3a2 was severely inhibited at the physiological
      salt concentration. Interestingly, the activity of Dnmt3a2 was significantly
      detected in the presence of Dnmt3L even at the physiological salt concentration.
      This indicates that Dnmt3a2 functions only in the presence of Dnmt3L in male
      gonocytes, and may explain why Dnmt3L is required specifically in mouse gonocytes
      for DNA methylation.

PMID- 16945938
TI  - A Monte Carlo sampling method of amino acid sequences adaptable to given main
      chain atoms in the proteins.
AB  - We have developed a computational method of protein design to detect amino acid
      sequences that are adaptable to given main-chain coordinates of a protein. In
      this method, the selection of amino acid types employs a Metropolis Monte Carlo
      method with a scoring function in conjunction with the approximation of free
      energies computed from 3D structures. To compute the scoring function, a side
      chain prediction using another Metropolis Monte Carlo method was performed to
      select structurally suitable side-chain conformations from a side-chain library.
      In total, two layers of Monte Carlo procedures were performed, first to select
      amino acid types (1st layer Monte Carlo) and then to predict side-chain
      conformations (2nd layers Monte Carlo). We applied this method to sequence design
      for the entire sequence on the SH3 domain, Protein G, and BPTI. The predicted
      sequences were similar to those of the wild-type proteins. We compared the
      results of the predictions with and without the 2nd layer Monte Carlo method. The
      results revealed that the two-layer Monte Carlo method produced better sequence
      similarity to the wild-type proteins than the one-layer method. Finally, we
      applied this method to neuraminidase of influenza virus. The results were
      consistent with the sequences identified from the isolated viruses.

PMID- 16945939
TI  - Crystal structure of TTHA0252 from Thermus thermophilus HB8, a RNA degradation
      protein of the metallo-beta-lactamase superfamily.
AB  - In bacterial RNA metabolism, mRNA degradation is an important process for gene
      expression. Recently, a novel ribonuclease (RNase), belonging to the beta-CASP
      family within the metallo-beta-lactamase superfamily, was identified as a
      functional homologue of RNase E, a major component for mRNA degradation in
      Escherichia coli. Here, we have determined the crystal structure of TTHA0252 from
      Thermus thermophilus HB8, which represents the first report of the tertiary
      structure of a beta-CASP family protein. TTHA0252 comprises two separate domains:
      a metallo-beta-lactamase domain and a "clamp" domain. The active site of the
      enzyme is located in a cleft between the two domains, which includes two zinc
      ions coordinated by seven conserved residues. Although this configuration is
      similar to those of other beta-lactamases, TTHA0252 has one conserved His residue
      characteristic of the beta-CASP family as a ligand. We also detected nuclease
      activity of TTHA0252 against rRNAs of T. thermophilus. Our results reveal
      structural and functional aspects of novel RNase E-like enzymes with a beta-CASP
      fold.

PMID- 16945940
TI  - Childhood leukaemia and socioeconomic status: fact or artefact? A report from the
      United Kingdom childhood cancer study (UKCCS).
AB  - BACKGROUND: It is widely believed that children of high socioeconomic status
      (SES) are more likely than those of low SES to develop acute lymphoblastic
      leukaemia (ALL). Such observations have led to wide-ranging speculations about
      the potential aetiological role of factors associated with affluence and
      modernization. METHODS: Children (0-14 years) newly diagnosed with cancer in the
      UK between 1991 and 1996 were ascertained via a rapid hospital-based case finding
      system (n = 4430, of which 1578 were ALL). Children without cancer (controls)
      were randomly selected from primary care population registries for comparative
      purposes (n = 7763). Area-based deprivation scores were assigned as markers of
      SES at two time points - birth and diagnosis. An individual-based marker of SES -
      social class - was assigned using father's occupation as recorded on the child's
      birth certificate. RESULTS: No differences in area-based measures of deprivation
      were observed between cases and controls at time of diagnosis, either for all
      cancers combined [n = 4430, odds ratio (OR) = 1.00 (95% confidence intervals (CI)
      0.98-1.01)] or for ALL alone (n = 1578 OR = 0.99, 95%CI 0.96-1.01). Findings were
      similar at time of birth (all cancers, OR = 0.99 95%CI 0.98-1.01, ALL OR = 0.98,
      95%CI 0.96-1.00). In addition, no case-control differences were observed when an
      individual-based measure of SES - social class - based on father's occupation at
      time of birth was used. CONCLUSIONS: The comprehensive nature of the data,
      coupled with complete case-ascertainment and representative population-based
      controls suggests that SES in the UK is not a determinant of ALL in children. We
      believe the small effects reported for SES in some past studies may be
      artefactual.

PMID- 16945942
TI  - The changing AMPK expression profile in differentiating mouse skeletal muscle
      myoblast cells helps confer increasing resistance to apoptosis.
AB  - AMP-activated protein kinase (AMPK) functions as a alpha/beta/gamma heterotrimer
      to preserve ATP levels and so cell viability during stressful conditions.
      However, its role in aiding survival of adult skeletal muscle precursor cells is
      unclear. Using the differentiating mouse C2C12 postnatal skeletal muscle myoblast
      cell line, we have determined that proteins for the AMPK subunit isoforms alpha2
      and gamma2 are constitutively expressed, while those for alpha1, beta1 and beta2
      are undetectable in undifferentiated myoblasts but increasingly expressed with
      differentiation to myotubes. Although the gamma3 subunit is expressed at a low
      level in myoblasts, it too is expressed increasingly with differentiation to
      myotubes. The p50 but not the p72 isoform of the embryonic alpha subunit
      homologue MELK is expressed only in proliferating myoblasts, while the ARK5 alpha
      subunit homologue is increasingly expressed with differentiation. Myotubes
      displayed higher basal and stimulated alpha1/alpha2 AMPK activation than
      myoblasts. Furthermore, serum starvation resulted in less apoptosis of
      differentiated myotubes than of undifferentiated myoblasts. This reflects, in
      part, the increased expression of functional AMPK in the myotubes, since specific
      inhibition of AMPK activity with 6-[4-(2-piperidin-1-ylethoxy)-phenyl]-3-pyridin
      4-ylpyrazolo[1,5-alpha] pyrimidine (Compound C) exacerbated the apoptosis
      resulting from serum withdrawal. If these in vitro events can also occur in vivo,
      they could have implications for pathologies such as muscle wasting, in which
      undifferentiated satellite stem cells may be easier apoptotic targets than their
      differentiated counterparts. Furthermore, these results suggest that when
      interpreting results from in vitro or in vivo experiments on AMPK, the subunit
      expression profile should be taken into account.

PMID- 16945943
TI  - Prostaglandin E2 release in gastric antral mucosa of guinea-pigs: basal PGE2
      release by cyclo-oxygenase 2 and ACh-stimulated PGE2 release by cyclo-oxygenase
      1.
AB  - Prostaglandin E(2) (PGE(2)), which is generated by two isoforms of cyclo
      oxygenase (COX(1) and COX(2)), is a key mediator in gastric mucosal defense. In
      the present study, antral mucosa of guinea-pigs was incubated with various
      agonists or antagonists in a medium, the PGE(2) concentration of which was
      measured using a PGE(2) EIA kit. Prostaglandin E(2) was released from the antral
      mucosa spontaneously (basal PGE(2) release) and acetylcholine (ACh, 10 microM)
      enhanced the PGE(2) release (ACh-stimulated PGE(2) release) was mediated via
      intracellular Ca(2+) concentration ([Ca(2+)](i)). Arachidonic acid enhanced both
      forms of PGE(2) release, and a phospholipase A(2) inhibitor (amylcinnamoyl
      anthranilic acid) and COX inhibitors (acetylsalicylic acid and indomethacin)
      decreased them. 5-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazol
      (SC560, 100 nm, a COX(1)-selective inhibitor) inhibited ACh-stimulated PGE(2)
      release without any decrease in basal PGE(2) release. N-(2-Cyclohexyloxy-4
      nitrophenyl) methanesulphonamide (NS398, 20 microM, a COX(2)-selective inhibitor)
      decreased basal PGE(2) release without any reduction of ACh-stimulated PGE(2)
      release. However, ionomycin (a Ca(2+) ionophore) increased PGE(2) release from
      antral mucosa in the presence of SC560 or NS398, suggesting that COX(1) and
      COX(2) are regulated by [Ca(2+)](i). These findings indicate that COX(1)
      containing cells have ACh receptors but COX(2)-containing cells do not. Moreover,
      in isolated antral epithelial cells, SC560 decreased basal and ACh-stimulated
      PGE(2) release, but NS398 did not. In conclusion, in antral mucosa, basal PGE(2)
      release is mainly maintained by COX(2) of non-epithelial cells, and ACh
      stimulated PGE(2) release is maintained by COX(1) of epithelial cells.

PMID- 16945944
TI  - IndexToolkit: an open source toolbox to index protein databases for high
      throughput proteomics.
AB  - A software package, IndexToolkit, aimed at overcoming the disadvantage of FASTA
      format databases for frequent searching, is developed to utilize an indexing
      strategy to substantially accelerate sequence queries. IndexToolkit includes user
      friendly tools and an Application Programming Interface (API) to facilitate
      indexing, storage and retrieval of protein sequence databases. As open source, it
      provides a sequence-retrieval developing framework, which is easily extensible
      for high-speed-request proteomic applications, such as database searching or
      modification discovering. We applied IndexToolkit to database searching engine
      pFind to demonstrate its effect. Experimental studies show that IndexToolkit is
      able to support significantly faster searches of protein database. AVAILABILITY:
      The IndexToolkit is free to use under the open source GNU GPL license. The source
      code and the compiled binary can be freely accessed through the website
      http://pfind.jdl.ac.cn/IndexToolkit. In this website, the more detailed
      information including screenshots and documentations for users and developers is
      also available.

PMID- 16945945
TI  - PSoL: a positive sample only learning algorithm for finding non-coding RNA genes.
AB  - MOTIVATION: Small non-coding RNA (ncRNA) genes play important regulatory roles in
      a variety of cellular processes. However, detection of ncRNA genes is a great
      challenge to both experimental and computational approaches. In this study, we
      describe a new approach called positive sample only learning (PSoL) to predict
      ncRNA genes in the Escherichia coli genome. Although PSoL is a machine learning
      method for classification, it requires no negative training data, which, in
      general, is hard to define properly and affects the performance of machine
      learning dramatically. In addition, using the support vector machine (SVM) as the
      core learning algorithm, PSoL can integrate many different kinds of information
      to improve the accuracy of prediction. Besides the application of PSoL for
      predicting ncRNAs, PSoL is applicable to many other bioinformatics problems as
      well. RESULTS: The PSoL method is assessed by 5-fold cross-validation experiments
      which show that PSoL can achieve about 80% accuracy in recovery of known ncRNAs.
      We compared PSoL predictions with five previously published results. The PSoL
      method has the highest percentage of predictions overlapping with those from
      other methods.

PMID- 16945946
TI  - Phytogeographical analysis of seed plant genera in China.
AB  - BACKGROUND AND AIMS: A central goal of biogeography and ecology is to uncover and
      understand distributional patterns of organisms. China has long been a focus of
      attention because of its rich biota, especially with respect to plants. Using 290
      floras from across China, this paper quantitatively characterizes the composition
      of floristic elements at multiple scales (i.e. national, provincial and local),
      and explores the extent to which climatic and geographical factors associated
      with each flora can jointly and independently explain the variation in floristic
      elements in local floras. METHODS: A study was made of 261 local floras, 28
      province-level floras and one national-level flora across China. Genera of seed
      plants in each flora were assigned to 14 floristic elements according to their
      worldwide geographical distributions. The composition of floristic elements was
      related to climatic and geographical factors. KEY RESULTS AND CONCLUSIONS:
      Variations in percentages of cosmopolitan, tropical and temperate genera among
      local floras tend to be greater at higher latitudes than at lower latitudes.
      Latitude is strongly correlated with the proportions of 13 of the 14 floristic
      elements. Correlations of the proportions of floristic elements with longitude
      are much weaker than those with latitude. Climate represented by the first
      principal component of a principal component analysis was strongly correlated
      with the proportions of floristic elements in local floras (|r| = 0.75 +/- 0.18).
      Geographical coordinates independently explained about four times as much
      variation in floristic elements as did climate. Further research is necessary to
      examine the roles of water-energy dynamics, geology, soils, biotic interactions,
      and historical factors such as land connections between continents in the past
      and at present in creating observed floristic patterns.

PMID- 16945947
TI  - Extensive clonality and strong differentiation in the insular pacific tree
      Santalum insulare: implications for its conservation.
AB  - BACKGROUND AND AIMS: The impact of evolutionary forces on insular systems is
      particularly exacerbated by the remoteness of islands, strong founder effects,
      small population size and the influence of biotic and abiotic factors. Patterns
      of molecular diversity were analysed in an island system with Santalum insulare,
      a sandalwood species endemic to eastern Polynesia. The aims were to evaluate
      clonality and to study the genetic diversity and structure of this species, in
      order to understand the evolutionary process and to define a conservation
      strategy. METHODS: Eight nuclear microsatellites were used to investigate
      clonality, genetic variation and structure of the French Polynesian sandalwood
      populations found on ten islands distributed over three archipelagos. KEY
      RESULTS: It was found that 58 % of the 384 trees analysed were clones. The real
      size of the populations is thus dramatically reduced, with sometimes only one
      genet producing ramets by root suckering. The diversity parameters were low for
      islands (n(A) = 1.5-5.0; H(E) = 0.28-0.49). No departure from Hardy-Weinberg
      proportion was observed except within Tahiti island, where a significant excess
      of homozygotes was noted in the highland population. Genetic structure was
      characterized by high levels of differentiation between archipelagos (27 % of the
      total variation) and islands (F(ST) = 0.50). The neighbour-joining tree did not
      discriminate the three archipelagos but separated the Society archipelago from
      the other two. CONCLUSIONS: This study shows that clonality is a frequent
      phenomenon in S. insulare. The genetic diversity within populations is lower than
      the values assessed in species distributed on the mainland, as a consequence of
      insularity. But this can also be explained by the overexploitation of sandalwood.
      The differentiation between archipelagos and islands within archipelagos is very
      high because of the limited gene flow due to oceanic barriers. Delineation of
      evolutionary significant units and principles for population management are
      proposed based on this molecular analysis.

PMID- 16945948
TI  - Tobacco plastid ribosomal protein S18 is essential for cell survival.
AB  - Plastid genomes contain a conserved set of genes most of which are involved in
      either photosynthesis or gene expression. Among the ribosomal protein genes
      present in higher plant plastid genomes, rps18 is special in that it is absent
      from the plastid genomes of several non-green unicellular organisms, including
      Euglena longa and Toxoplasma gondii. Here we have tested whether the ribosomal
      protein S18 is required for translation by deleting the rps18 gene from the
      tobacco plastid genome. We report that, while deletion of the rps18 gene was
      readily obtained, no homoplasmic Deltarps18 plants or leaf sectors could be
      isolated. Instead, segregation into homoplasmy led to severe defects in leaf
      development suggesting that the knockout of rps18 is lethal and the S18 protein
      is required for cell survival. Our data demonstrate that S18 is indispensable for
      plastid ribosome function in tobacco and support an essential role for plastid
      translation in plant development. Moreover, we demonstrate the occurrence of flip
      flop recombination on short inverted repeat sequences which generates different
      isoforms of the transformed plastid genome that differ in the orientation a 70 kb
      segment in the large single-copy region. However, infrequent occurrence of flip
      flop recombination and random segregation of plastid genomes result in the
      predominant presence of only one of the isoforms in many tissue samples.
      Implications for the interpretation of chloroplast transformation experiments and
      vector design are discussed.

PMID- 16945949
TI  - A mass spectrometry-based approach for identifying novel DNA polymerase
      substrates from a pool of dNTP analogues.
AB  - There has been a long-standing interest in the discovery of unnatural nucleotides
      that can be incorporated into DNA by polymerases. However, it is difficult to
      predict which nucleotide analogs will prove to have biological relevance.
      Therefore, we have developed a new screening method to identify novel substrates
      for DNA polymerases. This technique uses the polymerase itself to select a dNTP
      from a pool of potential substrates via incorporation onto a short
      oligonucleotide. The unnatural nucleotide(s) is then identified by high
      resolution mass spectrometry. By using a DNA polymerase as a selection tool, only
      the biologically relevant members of a small nucleotide library can be quickly
      determined. We have demonstrated that this method can be used to discover
      unnatural base pairs in DNA with a detection threshold of < or =10%
      incorporation.

PMID- 16945950
TI  - CAG*CTG repeat instability in cultured human astrocytes.
AB  - Cells of the central nervous system (CNS) are prone to the devastating
      consequences of trinucleotide repeat (TNR) expansion. Some CNS cells, including
      astrocytes, show substantial TNR instability in affected individuals. Since
      astrocyte enrichment occurs in brain regions sensitive to neurodegeneration and
      somatic TNR instability, immortalized SVG-A astrocytes were used as an ex vivo
      model to mimic TNR mutagenesis. Cultured astrocytes produced frequent (up to 2%)
      CAG.CTG contractions in a sequence-specific fashion, and an apparent threshold
      for instability was observed between 25 and 33 repeats. These results suggest
      that cultured astrocytes recapitulate key features of TNR mutagenesis.
      Furthermore, contractions were influenced by DNA replication through the repeat,
      suggesting that instability can arise by replication-based mechanisms in these
      cells. This is a crucial mechanistic point, since astrocytes in the CNS retain
      proliferative capacity throughout life and could be vulnerable to replication
      mediated TNR instability. The presence of interruptions led to smaller but more
      frequent contractions, compared to a pure repeat, and the interruptions were
      sometimes deleted to form a perfect tract. In summary, we suggest that CAG.CTG
      repeat instability in cultured astrocytes is dynamic and replication-driven,
      suggesting that TNR mutagenesis may be influenced by the proliferative capacity
      of key CNS cells.

PMID- 16945951
TI  - Transcriptional and phenotypic comparisons of Ppara knockout and siRNA knockdown
      mice.
AB  - RNA interference (RNAi) has great potential as a tool for studying gene function
      in mammals. However, the specificity and magnitude of the in vivo response to
      RNAi remains to be fully characterized. A molecular and phenotypic comparison of
      a genetic knockout mouse and the corresponding knockdown version would help
      clarify the utility of the RNAi approach. Here, we used hydrodynamic delivery of
      small interfering RNA (siRNA) to knockdown peroxisome proliferator activated
      receptor alpha (Ppara), a gene that is central to the regulation of fatty acid
      metabolism. We found that Ppara knockdown in the liver results in a transcript
      profile and metabolic phenotype that is comparable to those of Ppara-/- mice.
      Combining the profiles from mice treated with the PPARalpha agonist fenofibrate,
      we confirmed the specificity of the RNAi response and identified candidate genes
      proximal to PPARalpha regulation. Ppara knockdown animals developed hypoglycemia
      and hypertriglyceridemia, phenotypes observed in Ppara-/- mice. In contrast to
      Ppara-/- mice, fasting was not required to uncover these phenotypes. Together,
      these data validate the utility of the RNAi approach and suggest that siRNA can
      be used as a complement to classical knockout technology in gene function
      studies.

PMID- 16945953
TI  - Systematic identification of pseudogenes through whole genome expression evidence
      profiling.
AB  - The identification of pseudogenes is an integral and significant part of the
      genome annotation because of their abundance and their impact on the experimental
      analysis of functional genes. Most of the computational annotation systems are
      not optimized for systematic pseudogene recognition, often annotating pseudogenes
      as functional genes, and users then propagate these errors to subsequent analyses
      and interpretations. In order to validate gene annotations and to identify
      pseudogenes that are potentially mis-annotated, we developed a novel approach
      based on whole genome profiling of existing transcript and protein sequences.
      This method has two important features: (i) equally detects both processed and
      non-processed pseudogenes and (ii) can identify transcribed pseudogenes. Applying
      this method to the human Ensembl gene predictions, we discovered that 2011 (9% of
      total) Ensembl genes in the categories of known and novel might be pseudogenes
      based on expression evidence. Of these, 1200 genes are found to have no existing
      evidence of transcription, and 811 genes are found with transcription evidence
      but contain significant translation disruption. Approximately 40% of the 2011
      identified pseudogenes presented a multi-exon structure, representing non
      processed pseudogenes. We have demonstrated the power of whole genome profiling
      of expression sequences to improve the accuracy of gene annotations.

PMID- 16945952
TI  - Tapping diversity lost in transformations--in vitro amplification of ligation
      reactions.
AB  - Molecular evolution is a powerful means of engineering proteins. It usually
      requires the generation of a large recombinant DNA library of variants for
      cloning into a phage or plasmid vector, and the transformation of a host organism
      for expression and screening of the variant proteins. However, library size is
      often limited by the low yields of circular DNA and the poor transformation
      efficiencies of linear DNA. Here we have overcome this limitation by
      amplification of recombinant circular DNA molecules directly from ligation
      reactions. The amplification by bacteriophage Phi29 polymerase increased the
      number of transformants; thus from a nanogram-scale ligation of DNA fragments
      comprising two sub-libraries of variant antibody domains, we succeeded in
      amplifying a highly diverse and large combinatorial phage antibody library
      (>10(9) transformants in Escherichia coli and 10(5)-fold more transformants than
      without amplification). From the amplified library, but not from the smaller un
      amplified library, we could isolate several antibody fragments against a target
      antigen. It appears that amplification of ligations with Phi29 polymerase can
      help recover clones and molecular diversity otherwise lost in the transformation
      step. A further feature of the method is the option of using PCR-amplified
      vectors for ligations.

PMID- 16945954
TI  - Tumor inhibition by genomically integrated inducible RNAi-cassettes.
AB  - RNA interference (RNAi) has emerged as a powerful tool to induce loss-of-function
      phenotypes by post-transcriptional silencing of gene expression. In this study we
      wondered whether inducible RNAi-cassettes integrated into cellular DNA possess
      the power to trigger neoplastic growth. For this purpose inducible RNAi vectors
      containing tetracycline (Tet)-responsive derivatives of the H1 promoter for the
      conditional expression of short hairpin RNA (shRNA) were used to target human
      polo-like kinase 1 (Plk1), which is overexpressed in a broad spectrum of human
      tumors. In the absence of doxycycline (Dox) HeLa clones expressing TetR, that
      carry the RNAi-cassette stably integrated, exhibited no significant alteration in
      Plk1 expression levels. In contrast, exposure to Dox led to marked downregulation
      of Plk1 mRNA to 3% and Plk1 protein to 14% in cell culture compared to mismatch
      shRNA/Plk1-expressing cells. As a result of Plk1 depletion cell proliferation
      decreased to 17%. Furthermore, for harnessing RNAi for silencing disease-related
      genes in vivo we transplanted inducible RNAi-HeLa cells onto nude mice. After
      administration of Dox knockdown of Plk1 expression was observed correlating to a
      significant inhibition of tumor growth. Taken together, our data revealed that
      genomically integrated RNAi-elements are suitable to hamper tumor growth by
      conditional expression of shRNA.

PMID- 16945955
TI  - Structure of an archaeal PCNA1-PCNA2-FEN1 complex: elucidating PCNA subunit and
      client enzyme specificity.
AB  - The archaeal/eukaryotic proliferating cell nuclear antigen (PCNA) toroidal clamp
      interacts with a host of DNA modifying enzymes, providing a stable anchorage and
      enhancing their respective processivities. Given the broad range of enzymes with
      which PCNA has been shown to interact, relatively little is known about the mode
      of assembly of functionally meaningful combinations of enzymes on the PCNA clamp.
      We have determined the X-ray crystal structure of the Sulfolobus solfataricus
      PCNA1-PCNA2 heterodimer, bound to a single copy of the flap endonuclease FEN1 at
      2.9 A resolution. We demonstrate the specificity of interaction of the PCNA
      subunits to form the PCNA1-PCNA2-PCNA3 heterotrimer, as well as providing a
      rationale for the specific interaction of the C-terminal PIP-box motif of FEN1
      for the PCNA1 subunit. The structure explains the specificity of the individual
      archaeal PCNA subunits for selected repair enzyme 'clients', and provides
      insights into the co-ordinated assembly of sequential enzymatic steps in PCNA
      scaffolded DNA repair cascades.

PMID- 16945956
TI  - Crystallization and characterization of the thallium form of the Oxytricha nova G
      quadruplex.
AB  - The crystal structure of the Tl+ form of the G-quadruplex formed from the
      Oxytricha nova telomere sequence, d(G4T4G4), has been solved to 1.55 A. This G
      quadruplex contains five Tl+ ions, three of which are interspersed between
      adjacent G-quartet planes and one in each of the two thymine loops. The structure
      displays a high degree of similarity to the K+ crystal structure [Haider et al.
      (2002), J. Mol. Biol., 320, 189-200], including the number and location of the
      monovalent cation binding sites. The highly isomorphic nature of the two
      structures, which contain such a large number of monovalent binding sites
      (relative to nucleic acid content), verifies the ability of Tl+ to mimic K+ in
      nucleic acids. Information from this report confirms and extends the assignment
      of 205Tl resonances from a previous report [Gill et al. (2005), J. Am. Chem.
      Soc., 127, 16 723-16 732] where 205Tl NMR was used to study monovalent cation
      binding to this G-quadruplex. The assignment of these resonances provides
      evidence for the occurrence of conformational dynamics in the thymine loop region
      that is in slow exchange on the 205Tl timescale.

PMID- 16945957
TI  - Identification of miRNA targets with stable isotope labeling by amino acids in
      cell culture.
AB  - miRNAs are small noncoding RNAs that regulate gene expression. We have used
      stable isotope labeling by amino acids in cell culture (SILAC) to investigate the
      effect of miRNA-1 on the HeLa cell proteome. Expression of 12 out of 504
      investigated proteins was repressed by miRNA-1 transfection. This repressed set
      of genes significantly overlaps with miRNA-1 regulated genes that have been
      identified with DNA array technology and are predicted by computational methods.
      Moreover, we find that the 3'-untranslated region for the repressed set are
      enriched in miRNA-1 complementary sites. Our findings demonstrate that SILAC can
      be used for miRNA target identification and that one highly expressed miRNA can
      regulate the levels of many different proteins.

PMID- 16945958
TI  - Competition for RISC binding predicts in vitro potency of siRNA.
AB  - Short interfering RNAs (siRNA) guide degradation of target RNA by the RNA-induced
      silencing complex (RISC). The use of siRNA in animals is limited partially due to
      the short half-life of siRNAs in tissues. Chemically modified siRNAs are
      necessary that maintain mRNA degradation activity, but are more stable to
      nucleases. In this study, we utilized alternating 2'-O-methyl and 2'-deoxy-2'
      fluoro (OMe/F) chemically modified siRNA targeting PTEN and Eg5. OMe/F-modified
      siRNA consistently reduced mRNA and protein levels with equal or greater potency
      and efficacy than unmodified siRNA. We showed that modified siRNAs use the RISC
      mechanism and lead to cleavage of target mRNA at the same position as unmodified
      siRNA. We further demonstrated that siRNAs can compete with each other, where
      highly potent siRNAs can compete with less potent siRNAs, thus limiting the
      ability of siRNAs with lower potency to mediate mRNA degradation. In contrast, a
      siRNA with low potency cannot compete with a highly efficient siRNA. We
      established a correlation between siRNA potency and ability to compete with other
      siRNAs. Thus, siRNAs that are more potent inhibitors for mRNA destruction have
      the potential to out-compete less potent siRNAs indicating that the amount of a
      cellular component, perhaps RISC, limits siRNA activity.

PMID- 16945959
TI  - A modified thymine for the synthesis of site-specific thymine-guanine DNA
      interstrand crosslinks.
AB  - DNA interstrand crosslinks (ICLs) are highly cytotoxic lesions formed by a
      variety of important anti-tumor agents. Despite the clinical importance of ICLs,
      the mechanisms by which these lesions are repaired in mammalian cells have so far
      remained elusive. One of the obstacles in the study of ICL repair has been the
      limited availability of suitable methods for the synthesis of defined site
      specific ICLs. We report here the synthesis of a site-specific ICL containing an
      ethylene-bridged G-T base pair based on the incorporation of a crosslink
      precursor containing a selectively reactive group on one strand using solid-phase
      synthesis. 3-(2-chloroethyl)thymidine was incorporated into oligonucleotides and
      underwent ICL formation upon annealing to a complementary strand by reacting with
      the base opposite to the modified T residue. A strong preference for ICL
      formation with a G residue opposite the reactive T was observed. Detailed
      characterization of the reaction product revealed that the alkylation reaction
      occurred with the O-6 group of G and a mechanism accounting for this preference
      is proposed. These G-T crosslinks introduced here will be useful for studies of
      ICL repair.

PMID- 16945960
TI  - Solution structure of the apical stem-loop of the human hepatitis B virus
      encapsidation signal.
AB  - Hepatitis B virus (HBV) replication is initiated by HBV RT binding to the highly
      conserved encapsidation signal, epsilon, at the 5' end of the RNA pregenome.
      Epsilon contains an apical stem-loop, whose residues are either totally conserved
      or show rare non-disruptive mutations. Here we present the structure of the
      apical stem-loop based on NOE, RDC and (1)H chemical shift NMR data. The (1)H
      chemical shifts proved to be crucial to define the loop conformation. The loop
      sequence 5'-CUGUGC-3' folds into a UGU triloop with a CG closing base pair and a
      bulged out C and hence forms a pseudo-triloop, a proposed protein recognition
      motif. In the UGU loop conformations most consistent with experimental data, the
      guanine nucleobase is located on the minor groove face and the two uracil bases
      on the major groove face. The underlying helix is disrupted by a conserved non
      paired U bulge. This U bulge adopts multiple conformations, with the nucleobase
      being located either in the major groove or partially intercalated in the helix
      from the minor groove side, and bends the helical stem. The pseudo-triloop motif,
      together with the U bulge, may represent important anchor points for the initial
      recognition of epsilon by the viral RT.

PMID- 16945961
TI  - The role of AtMUS81 in DNA repair and its genetic interaction with the helicase
      AtRecQ4A.
AB  - The endonuclease MUS81 has been shown in a variety of organisms to be involved in
      DNA repair in mitotic and meiotic cells. Homologues of the MUS81 gene exist in
      the genomes of all eukaryotes, pointing to a conserved role of the protein.
      However, the biological role of MUS81 varies between different eukaryotes. For
      example, while loss of the gene results in strongly impaired fertility in
      Saccharomyces cerevisiae and nearly complete sterility in Schizosaccharomyces
      pombe, it is not essential for meiosis in mammals. We identified a functional
      homologue (AtMUS81/At4g30870) in the genome of Arabidopsis thaliana and isolated
      a full-length cDNA of this gene. Analysing two independent T-DNA insertion lines
      of AtMUS81, we found that they are sensitive to the mutagens MMS and MMC. Both
      mutants have a deficiency in homologous recombination in somatic cells but only
      after induction by genotoxic stress. In contrast to yeast, no meiotic defect of
      AtMUS81 mutants was detectable and the mutants are viable. Crosses with a
      hyperrecombinogenic mutant of the AtRecQ4A helicase resulted in synthetic
      lethality in the double mutant. Thus, the nuclease AtMUS81 and the helicase
      AtRecQ4A seem to be involved in two alternative pathways of resolution of
      replicative DNA structures in somatic cells.

PMID- 16945963
TI  - Sympathetic activation by the central chemoreceptor 'reflex': new evidence that
      RVLM vasomotor neurons are involved...but are they enough?

PMID- 16945962
TI  - Stimulation of Dmc1-mediated DNA strand exchange by the human Rad54B protein.
AB  - The process of homologous recombination is indispensable for both meiotic and
      mitotic cell division, and is one of the major pathways for double-strand break
      (DSB) repair. The human Rad54B protein, which belongs to the SWI2/SNF2 protein
      family, plays a role in homologous recombination, and may function with the Dmc1
      recombinase, a meiosis-specific Rad51 homolog. In the present study, we found
      that Rad54B enhanced the DNA strand-exchange activity of Dmc1 by stabilizing the
      Dmc1-single-stranded DNA (ssDNA) complex. Therefore, Rad54B may stimulate the
      Dmc1-mediated DNA strand exchange by stabilizing the nucleoprotein filament,
      which is formed on the ssDNA tails produced at DSB sites during homologous
      recombination.

PMID- 16945964
TI  - Resonance (approximately 10 Hz) of excitatory networks in motor cortex: effects
      of voltage-dependent ion channel blockers.
AB  - The motor cortex generates synchronous network oscillations at frequencies
      between 7 and 14 Hz during disinhibition or low [Mg2+]o buffers, but the
      underlying mechanisms are poorly understood. These oscillations, termed here
      approximately 10 Hz oscillations, are generated by a purely excitatory network of
      interconnected pyramidal cells because they are robust in the absence of
      GABAergic transmission. It is likely that specific voltage-dependent currents
      expressed in those cells contribute to the generation of approximately 10 Hz
      oscillations. We tested the effects of different drugs known to suppress certain
      voltage-dependent currents. The results revealed that drugs that suppress the low
      threshold calcium current and the hyperpolarization-activated cation current are
      not critically involved in the generation of approximately 10 Hz oscillations.
      Interestingly, drugs known to suppress the persistent sodium current abolished
      approximately 10 Hz oscillations. Furthermore, blockers of K+ channels had
      significant effects on the oscillations. In particular, blockers of the M-current
      abolished the oscillations. Also, blockers of both non-inactivating and slowly
      inactivating voltage-dependent K+ currents abolished approximately 10 Hz
      oscillations. The results indicate that specific voltage-dependent non
      inactivating K+ currents, such as the M-current, and persistent sodium currents
      are critically involved in generating approximately 10 Hz oscillations of
      excitatory motor cortex networks.

PMID- 16945966
TI  - The self-regulating nature of spontaneous synchronized activity in developing
      mouse cortical neurones.
AB  - Waves of spontaneous electrical activity that are highly synchronized across
      large populations of neurones occur throughout the developing mammalian central
      nervous system. The stages at which this activity occurs are tightly regulated to
      allow activity-dependent developmental programmes to be initiated correctly. What
      determines the onset and cessation of spontaneous synchronous activity (SSA) in a
      particular region of the nervous system, however, remains unclear. We have tested
      the hypothesis that activity itself triggers developmental changes in intrinsic
      and circuit properties that determine the stages at which SSA occurs. To do this
      we exposed cultured slices of mouse neocortex to tetrodotoxin (TTX) to block SSA,
      which normally occurs between embryonic day 17 (E17) and postnatal day 3 (P3). In
      control cultured slices, SSA rarely occurs after P3. In TTX-treated slices,
      however, SSA was generated from P3 (the day of TTX removal) until at least P10.
      This indicates that in the absence of spontaneous activity, the mechanisms that
      normally determine the timing of SSA are not initiated, and that a compensatory
      response occurs that shifts the time of SSA occurrence to later developmental
      stages.

PMID- 16945965
TI  - Potentiation of mouse vagal afferent mechanosensitivity by ionotropic and
      metabotropic glutamate receptors.
AB  - Glutamate acts at central synapses via ionotropic (iGluR--NMDA, AMPA and kainate)
      and metabotropic glutamate receptors (mGluRs). Group I mGluRs are excitatory
      whilst group II and III are inhibitory. Inhibitory mGluRs also modulate
      peripherally the mechanosensitivity of gastro-oesophageal vagal afferents. Here
      we determined the potential of excitatory GluRs to play an opposing role in
      modulating vagal afferent mechanosensitivity, and investigated expression of
      receptor subunit mRNA within the nodose ganglion. The responses of mouse gastro
      oesophageal vagal afferents to graded mechanical stimuli were investigated before
      and during application of selective GluR ligands to their peripheral endings. Two
      types of vagal afferents were tested: tension receptors, which respond to
      circumferential tension, and mucosal receptors, which respond only to mucosal
      stroking. The selective iGluR agonists NMDA and AMPA concentration-dependently
      potentiated afferent responses. Their corresponding antagonists AP-5 and NBQX
      alone attenuated mechanosensory responses as did the non-selective antagonist
      kynurenate. The kainate selective agonist SYM-2081 had minor effects on
      mechanosensitivity, and the antagonist UBP 302 was ineffective. The mGluR5
      antagonist MTEP concentration-dependently inhibited mechanosensitivity. Efficacy
      of agonists and antagonists differed on mucosal and tension receptors. We
      conclude that excitatory modulation of afferent mechanosensitivity occurs mainly
      via NMDA, AMPA and mGlu5 receptors, and the role of each differs according to
      afferent subtypes. PCR data indicated that all NMDA, kainate and AMPA receptor
      subunits plus mGluR5 are expressed, and are therefore candidates for the
      neuromodulation we observed.

PMID- 16945967
TI  - Cytosolic energy reserves determine the effect of glycolytic sugar phosphates on
      sarcoplasmic reticulum Ca2+ release in cat ventricular myocytes.
AB  - Localization of glycolytic enzymes in close proximity to Ca(2+) transport systems
      of the sarcoplasmic reticulum (SR) in cardiac cells suggests an important
      functional role for glycolysis in intracellular [Ca(2+)] regulation and,
      consequently, excitation-contraction coupling. Here, we investigated the
      mechanisms of regulation of SR Ca(2+) release by glycolytic sugar phosphate
      intermediates in cat ventricular myocytes. Experiments with permeabilized
      myocytes revealed that with normal cytosolic energy reserves (mm: ATP 5, ADP
      0.01, phosphocreatine (CrP) 10) fructose-1,6-bisphosphate (FBP; 1 mm) and
      fructose-6-phosphate (F6P; 1 mm) caused a transient increase of Ca(2+) spark
      frequency by 62 and 42%, respectively. This effect of sugar phosphates was
      associated with a 13% decrease in SR Ca(2+) load. Pretreatment of the cells with
      an inhibitor of glycolysis, iodoacetate (IAA; 0.5 mm), did not prevent the
      effects of FBP and F6P on Ca(2+) sparks. Recording of single ryanodine receptor
      (RyR) channel activity indicated that FBP and F6P significantly increased RyR
      open probability. Reduction of cytosolic energy reserves decreased Ca(2+) spark
      activity. Increasing [ADP] to 0.4 mm or removal of CrP ([ATP] was kept constant)
      caused a slowly developing decrease of Ca(2+) spark frequency by 29 and 42%,
      respectively. Changing [ADP] and [CrP] simultaneously decreased Ca(2+) spark
      frequency by 66%. This inhibition of Ca(2+) sparks was associated with a 40%
      decrease in SR Ca(2+) load. The subsequent addition of FBP (1 mm) partially
      restored Ca(2+) spark frequency and SR Ca(2+) load. This recovery of Ca(2+)
      sparks was blocked completely by IAA. These data suggest that at physiological
      ATP, ADP and CrP levels accumulation of sugar phosphates from glycolysis can
      stimulate SR Ca(2+) release. This effect does not require the activity of
      downstream glycolytic enzymes, but rather is the result of direct activation of
      RyRs. However, under conditions associated with depletion of cellular energy
      reserves (e.g. myocardial ischaemia), ATP generated from glycolysis may play an
      important role in maintaining myocardial Ca(2+) homeostasis by improving SR
      Ca(2+) uptake.

PMID- 16945968
TI  - Factors modifying the frequency of spontaneous activity in gastric muscle.
AB  - The cellular mechanisms that determine the frequency of spontaneous activity were
      investigated in gastric smooth muscles isolated from the guinea-pig. Intact
      antral muscle generated slow waves periodically; the interval between slow waves
      was decreased exponentially by depolarization of the membrane to reach a steady
      interval value of about 7 s. Isolated circular muscle bundles produced slow
      potentials spontaneously or were evoked by depolarizing current stimuli. Evoked
      slow potentials appeared in an all-or-none fashion, with a refractory period of
      approximately 2-3 s. Low concentrations of chemicals that modify intracellular
      signalling revealed that the refractory period was causally related to the
      activity of protein kinase C (PKC). Activation of PKC increased and inhibition of
      PKC activity decreased the frequency of slow potentials. Chemicals that inhibit
      mitochondrial functions reduced the frequency of slow waves. Inhibition of
      internal Ca(2+)-store activity decreased the amplitude, but not the frequency of
      slow potentials, suggesting that the amplitude is causally related to Ca(2+)
      release from the internal store. The results suggest that changes in [Ca(2+)](i)
      caused by the activity of mitochondria may play a key role in determining the
      frequency of spontaneous activity in gastric pacemaker cells.

PMID- 16945969
TI  - Pyeloureteric peristalsis: role of atypical smooth muscle cells and interstitial
      cells of Cajal-like cells as pacemakers.
AB  - Pyeloureteric peristalsis has long been considered to be triggered by pacemaker
      atypical smooth muscle cells (SMC) located in the proximal regions of the renal
      pelvis. However, interstitial cells with many of the morphological features and c
      Kit immuno-reactivity of interstitial cells of Cajal (ICC), the established
      pacemaker cells in the intestine, have been demonstrated to be present in small
      numbers within the ureteropelvic junction (UPJ) of many mammals. Freshly isolated
      ICC-like cells (ICC-LC) of the mouse UPJ also display autorhyhmicity. This review
      discusses the notion that ureteric peristalsis depends on the presence of both
      atypical SMC and ICC-LC which form separate but interconnected networks that
      drive electrically quiescent typical SMC. In contrast to the intestine or
      prostate, all regenerative potential discharge in the mouse UPJ is abolished by
      the L-type Ca(2+) channel blocker nifedipine revealing a fundamental pacemaker
      signal. Whether these pacemaker transients arise from atypical SMC or ICC-LC or
      both has yet to be established. We speculate that the presence of spontaneously
      active ICC-LC in the distal regions of the UPJ maintains rudimentary peristaltic
      waves and movement of urine towards the bladder after pyeloureteral obstruction
      or pyeloplasty and disconnection from the proximal pacemaker drive.

PMID- 16945970
TI  - Interstitial cells of Cajal at the clinical and scientific interface.
AB  - Considerable work over the past two decades has determined that interstitial
      cells of Cajal (ICC) serve as pacemaker cells, conduits for active transmission
      of electrical slow waves, sites of innervation by peripheral motor neurons, and
      mechanotransducers. While most of the physiology of ICC has been learned from
      studies of the cells within the gastrointestinal tract, ICC are found in a
      variety of smooth muscle tissues and may have analogous or novel physiological
      functions in those organs. Clinical investigations of muscles from patients with
      a variety of gastrointestinal motility disorders have raised the exciting
      possibility that loss of ICC may be responsible for the development of motor
      dysfunction. This review discusses the development of ICC, the kinds of human
      disorders in which ICC loss may be important, what factors regulate the ICC
      phenotype, and what therapeutic approaches might be utilized to restore or
      regenerate ICC. This field is primed for translational discoveries. ICC are
      responsible for critical physiological functions in smooth muscle tissues, they
      are lost in pathophysiological conditions, and it will be important now to
      decipher the conditions that are responsible for ICC loss and develop new
      therapies to relieve patients of this problem. Success in this endeavour might
      improve the quality of life for millions of patients.

PMID- 16945971
TI  - Complex interplay between glutamate receptors and intracellular Ca2+ stores
      during ischaemia in rat spinal cord white matter.
AB  - Electrophysiological recordings of propagated compound action potentials (CAPs)
      and axonal Ca(2+) measurements using confocal microscopy were used to study the
      interplay between AMPA receptors and intracellullar Ca(2+) stores in rat spinal
      dorsal columns subjected to in vitro combined oxygen and glucose deprivation
      (OGD). Removal of Ca(2+) or Na(+) from the perfusate was protective after 30 but
      not 60 min of OGD. TTX was ineffective with either exposure, consistent with its
      modest effect on ischaemic depolarization. In contrast, AMPA antagonists were
      very protective, even after 60 min of OGD where 0Ca(2+) + EGTA perfusate was
      ineffective. Similarly, blocking ryanodine receptor-mediated Ca(2+) mobilization
      from internal stores (0Ca(2+) + nimodipine or 0Ca(2+) + ryanodine), or inositol
      1,4,5-trisphosphate (IP(3))-dependent Ca(2+) release (block of group 1
      metabotropic glutamate receptors with 1-aminoindan-1,5-dicarboxylic acid,
      inhibition of phospholipase C with U73122 or IP(3) receptor block with 2APB; each
      in 0Ca(2+)) were each very protective, with the combination resulting in
      virtually complete functional recovery after 1 h OGD (97 +/- 32% CAP recovery
      versus 4 +/- 6% in artificial cerebrospinal fluid). AMPA induced a rise in Ca(2+)
      concentration in normoxic axons, which was greatly reduced by blocking ryanodine
      receptors. Our data therefore suggest a novel and surprisingly complex interplay
      between AMPA receptors and Ca(2+) mobilization from intracellular Ca(2+) stores.
      We propose that AMPA receptors may not only allow Ca(2+) influx from the
      extracellular space, but may also significantly influence Ca(2+) release from
      intra-axonal Ca(2+) stores. In dorsal column axons, AMPA receptor-dependent
      mechanisms appear to exert a greater influence than voltage-gated Na(+) channels
      on functional outcome following OGD.

PMID- 16945972
TI  - Interaction between interstitial cells and smooth muscles in the lower urinary
      tract and penis.
AB  - Smooth muscles in the lower urinary tract and corporal tissue exhibit spontaneous
      contractile activity which depends on L-type Ca(2+) channels. The mechanism
      underlying this activity is spontaneous electrical activity which shows varied
      form and property between these tissues. Recent studies revealed that
      interstitial cells (ICs) are widely distributed in the genitourinary system, and
      suggested their involvement in spontaneous muscle activity. ICs in the system are
      not a simple analogy of interstitial cells of Cajal (ICC) in the gut, which act
      as electrical pacemaker, but represent variability amongst tissues which may
      account for individual characteristics of each organ. In the bladder and corporal
      tissue, where smooth muscle cells are capable of generating spontaneous
      electrical activity, ICs may modulate smooth muscle activity. ICs in corporal
      tissue release prostaglandins via cyclooxygenase-2 (COX-2) activity and reinforce
      not only spontaneous but also nerve-mediated alpha-adrenergic contractions. In
      the bladder, their fundamental role in the integration of signals between
      populations of cells has been proposed, and thus changes in ICs may contribute to
      an overactive bladder, a pathological condition which results from increased
      excitability in detrusor smooth muscles. In the urethra, ICs may act as
      electrical pacemakers as do ICC. However, overall contractility of urethral
      smooth muscles does not necessarily rely on pacemaking of ICs, and thus some
      population of smooth muscles may also have their own excitability.

PMID- 16945973
TI  - Intracellular calcium regulation among subpopulations of rat dorsal root ganglion
      neurons.
AB  - Primary afferent neurons are functionally heterogeneous. To determine whether
      this functional heterogeneity reflects, in part, heterogeneity in the regulation
      of the concentration of intracellular Ca(2+) ([Ca(2+)](i)), the magnitude and
      decay of evoked Ca(2+) transients were assessed in subpopulations of dorsal root
      ganglion (DRG) neurons with voltage clamp and fura-2 ratiometric imaging. To
      determine whether differences in evoked Ca(2+) transients among subpopulations of
      DRG neurons reflected differences in the contribution of Ca(2+) regulatory
      mechanisms, pharmacological techniques were employed to assess the contribution
      of influx, efflux, release and uptake pathways. Subpopulations of DRG neurons
      were defined by cell body size, binding of the plant lectin IB(4) and
      responsiveness to the algogenic compound capsaicin (CAP). Ca(2+) transients were
      evoked with 30 mm K(+) or voltage steps to 0 mV. There were marked differences
      between subpopulations of neurons with respect to both the magnitude and decay of
      the Ca(2+) transient, with the largest and most slowly decaying Ca(2+) transients
      in small-diameter, IB(4)-positive, CAP-responsive neurons. The smallest and most
      rapidly decaying transients were in large-diameter, IB(4)-negative and CAP
      unresponsive DRG neurons. These differences were not due to a differential
      distribution of voltage-gated Ca(2+) currents. However, these differences did
      appear to reflect a differential contribution of other influx, efflux, release
      and uptake mechanisms between subpopulations of neurons. These results suggest
      that electrical activity in subpopulations of DRG neurons will have a
      differential influence on Ca(2+)-regulated phenomena such as spike adaptation,
      transmitter release and gene transcription. Significantly more activity should be
      required in large-diameter non-nociceptive afferents than in small-diameter
      nociceptive afferents to have a comparable influence on these processes.

PMID- 16945974
TI  - Craniocentric body-sway responses to 500 Hz bone-conducted tones in man.
AB  - Whole-body responses evoked by bone-conducted sound, a stimulus known to activate
      vestibular afferents, were recorded in standing subjects deprived of vision. With
      the head facing forward, unilateral mastoid vibration (500 Hz, 2 s, 136 dB force
      level) produced an oblique body sway with a consistent lateral component away
      from the stimulated ear and an average forward component. The side of stimulation
      had a powerful influence on the direction but not the magnitude of sway.
      Individuals' mean response directions were significantly clustered between
      subjects, as well as within subjects for 12 of 16 subjects when tested on five
      occasions. Single trial analysis did not reveal any habituation of the response.
      To investigate whether muscle spindle activation might be responsible for the
      response, vibration was applied directly over posterior and anterior neck muscles
      and tendons. This generally produced responses that were smaller and with
      different direction characteristics than with mastoid vibration. In contrast,
      stimulation over the temporal fossa produced responses similar in magnitude and
      direction to mastoid stimulation. When the head was turned in yaw to face in
      different directions the sway response changed direction by the same amount but
      with no change in magnitude, suggesting response organization in a craniocentric
      reference frame. Whole-body sway evoked by 500 Hz vibration delivered over sites
      close to the ear is thus likely to represent a vestibular-evoked balance
      response. When compared with sway responses evoked by 500 Hz vibration of the
      left temporal fossa, responses to 1 mA left cathodal galvanic vestibular
      stimulation were of similar magnitude, yet significantly different in direction,
      suggesting differences in the end organ afferents activated by these two stimuli.
      This may enable investigation of previously inaccessible aspects of vestibular
      function in intact freely behaving human subjects.

PMID- 16945975
TI  - In vivo ATP production during free-flow and ischaemic muscle contractions in
      humans.
AB  - The aim of this study was to determine how ATP synthesis and contractility in
      vivo are altered by ischaemia in working human skeletal muscle. The hypotheses
      were: (1) glycolytic flux would be higher during ischaemic (ISC) compared to free
      flow (FF) muscle contractions, in compensation for reduced oxidative ATP
      synthesis, and (2) ischaemic muscle fatigue would be related to the accumulation
      of inhibitory metabolic by-products rather than to the phosphorylation potential
      ([ATP]/[ADP][P(i)]) of the muscle. Twelve healthy adults (6 men, 6 women)
      performed six intermittent maximal isometric contractions of the ankle
      dorsiflexors (12 s contract, 12 s relax), once with intact blood flow and once
      with local ischaemia by thigh cuff inflation to 220 Torr. Intracellular
      phosphorous metabolites and pH were measured non-invasively with magnetic
      resonance spectroscopy, and rates of ATP synthesis through oxidative
      phosphorylation, anaerobic glycolysis, and the creatine kinase reaction were
      determined. The force-time integral declined more during ISC (66 +/- 3% initial)
      than FF (75 +/- 2% initial, P = 0.002), indicating greater fatigue in ISC. [ATP]
      was preserved in both protocols, indicating matching of ATP production and use
      under both conditions. Glycolytic flux (mm s(-1)) was similar during FF and ISC
      (P = 0.16). Total ATP synthesis rate was lower during ISC, despite adjustment for
      the greater muscle fatigue in this condition (P < 0.001). Fatigue was linearly
      associated with diprotonated inorganic phosphate (FF r = 0.94 +/- 0.01, ISC r =
      0.92 +/- 0.02), but not phosphorylation potential. These data provide novel
      evidence that ATP supply and demand in vivo are balanced in human skeletal muscle
      during ischaemic work, not through higher glycolytic flux, but rather through
      increased metabolic economy and decreased rates of ATP consumption as fatigue
      ensues.

PMID- 16945976
TI  - Evidence that GABA rho subunits contribute to functional ionotropic GABA
      receptors in mouse cerebellar Purkinje cells.
AB  - Ionotropic gamma-amino butyric acid (GABA) receptors composed of heterogeneous
      molecular subunits are major mediators of inhibitory responses in the adult CNS.
      Here, we describe a novel ionotropic GABA receptor in mouse cerebellar Purkinje
      cells (PCs) using agents reported to have increased affinity for rho subunit
      containing GABA(C) over other GABA receptors. Exogenous application of the
      GABA(C)-preferring agonist cis-4-aminocrotonic acid (CACA) evoked whole-cell
      currents in PCs, whilst equimolar concentrations of GABA evoked larger currents.
      CACA-evoked currents had a greater sensitivity to the selective GABA(C)
      antagonist (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) than
      GABA-evoked currents. Focal application of agonists produced a differential
      response profile; CACA-evoked currents displayed a much more pronounced
      attenuation with increasing distance from the PC soma, displayed a slower time-to
      peak and exhibited less desensitization than GABA-evoked currents. However, CACA
      evoked currents were also completely blocked by bicuculline, a selective agent
      for GABA(A) receptors. Thus, we describe a population of ionotropic GABA
      receptors with a mixed GABA(A)/GABA(C) pharmacology. TPMPA reduced inhibitory
      synaptic transmission at interneurone-Purkinje cell (IN-PC) synapses, causing
      clear reductions in miniature inhibitory postsynaptic current (mIPSC) amplitude
      and frequency. Combined application of NO-711 (a selective GABA transporter
      subtype 1 (GAT-1) antagonist) and SNAP-5114 (a GAT-(2)/3/4 antagonist) induced a
      tonic GABA conductance in PCs; however, TPMPA had no effect on this current.
      Immunohistochemical studies suggest that rho subunits are expressed predominantly
      in PC soma and proximal dendritic compartments with a lower level of expression
      in more distal dendrites; this selective immunoreactivity contrasted with a more
      uniform distribution of GABA(A) alpha1 subunits in PCs. Finally, co
      immunoprecipitation studies suggest that rho subunits can form complexes with
      GABA(A) receptor alpha1 subunits in the cerebellar cortex. Overall, these data
      suggest that rho subunits contribute to functional ionotropic receptors that
      mediate a component of phasic inhibitory GABAergic transmission at IN-PC synapses
      in the cerebellum.

PMID- 16945977
TI  - Frequency-dependent selection of reflexes by pudendal afferents in the cat.
AB  - Activation of urethral or genital afferents of the pudendal nerve can elicit or
      inhibit micturition, and low frequency stimulation of the compound pudendal nerve
      (PN) is known to produce a continence response. The present study demonstrates
      that PN stimulation also can elicit a micturition-like response and that the
      response to PN stimulation is dependent on stimulation frequency. We measured the
      changes in bladder pressure and external urethral sphincter (EUS)
      electroneurogram (ENG) evoked by PN stimulation before and up to 16 h after
      spinal cord transection (SCT) in cats anaesthetized with alpha-chloralose. Low
      frequency (10 Hz) stimulation elicited a continence-like response, including
      inhibition of the bladder and activation of the EUS, but mid-frequency (33 Hz)
      stimulation produced a micturition-like response, including excitation of the
      bladder without activation of the EUS. The dependence of the response on stimulus
      frequency was linked to interpulse interval as the same number of pulses at 10,
      33 and 100 Hz produced different responses. Stimulation of the PN at 33 Hz
      produced bladder contractions before and 8 h after SCT provided the bladder
      contained a minimum volume of fluid. Only mid-range frequency stimulation with
      sufficient stimulus train duration produced a reduction in EUS ENG activity
      before and after SCT. In addition to a continence-like response, PN stimulation
      can also elicit a micturition-like response, and this response is dependent on
      stimulation frequency, stimulus train duration, and bladder volume. The ability
      to control the two principal functions of the bladder by pudendal nerve
      stimulation is an exciting prospect for neurorehabilitation.

PMID- 16945978
TI  - Sex differences in cortical thickness mapped in 176 healthy individuals between 7
      and 87 years of age.
AB  - Findings from previous magnetic resonance imaging studies of sex differences in
      gray matter have been inconsistent, with some showing proportionally increased
      gray matter in women and some showing no differences between the sexes. Regional
      sex differences in gray matter thickness have not yet been mapped over the entire
      cortical surface in a large sample of subjects spanning the age range from early
      childhood to old age. We applied algorithms for cortical pattern matching and
      techniques for measuring cortical thickness to the structural magnetic resonance
      images of 176 healthy individuals between the ages of 7 and 87 years. We also
      mapped localized differences in brain size. Maps of sex differences in cortical
      thickness revealed thicker cortices in women in right inferior parietal and
      posterior temporal regions even without correcting for total brain volume. In
      these regions, the cortical mantle is up to 0.45 mm thicker, on average, in women
      than in men. Analysis of a subset of 18 female and 18 male subjects matched for
      age and brain volume confirmed the significance of thicker gray matter in
      temporal and parietal cortices in females, independent of brain size differences.
      Further analyses were conducted in the adult subjects where gender differences
      were evaluated using height as a covariate, and similar sex differences were
      observed even when body size differences between the sexes were controlled.
      Together, these results suggest that greater cortical thickness in posterior
      temporal inferior parietal regions in females relative to males are independent
      of differences in brain or body size. Age-by-sex interactions were not
      significant in the temporoparietal region, suggesting that sex differences in
      these regions are present from at least late childhood and then are maintained
      throughout life. Male brains were larger than female brains in all locations,
      though male enlargement was most prominent in the frontal and occipital poles,
      bilaterally. Given the large sample and the large range of ages studied, these
      results help to address controversies in the study of central nervous system
      sexual dimorphisms.

PMID- 16945979
TI  - Insights into early extracellular matrix evolution: spongin short chain collagen
      related proteins are homologous to basement membrane type IV collagens and form a
      novel family widely distributed in invertebrates.
AB  - Collagens are thought to represent one of the most important molecular
      innovations in the metazoan line. Basement membrane type IV collagen is present
      in all Eumetazoa and was found in Homoscleromorpha, a sponge group with a well
      organized epithelium, which may represent the first stage of tissue
      differentiation during animal evolution. In contrast, spongin seems to be a
      demosponge-specific collagenous protein, which can totally substitute an
      inorganic skeleton, such as in the well-known bath sponge. In the freshwater
      sponge Ephydatia mulleri, we previously characterized a family of short-chain
      collagens that are likely to be main components of spongins. Using a combination
      of sequence- and structure-based methods, we present evidence of remote homology
      between the carboxyl-terminal noncollagenous NC1 domain of spongin short-chain
      collagens and type IV collagen. Unexpectedly, spongin short-chain collagen
      related proteins were retrieved in nonsponge animals, suggesting that a family
      related to spongin constitutes an evolutionary sister to the type IV collagen
      family. Formation of the ancestral NC1 domain and divergence of the spongin short
      chain collagen-related and type IV collagen families may have occurred before the
      parazoan-eumetazoan split, the earliest divergence among extant animal phyla.
      Molecular phylogenetics based on NC1 domain sequences suggest distinct
      evolutionary histories for spongin short-chain collagen-related and type IV
      collagen families that include spongin short-chain collagen-related gene loss in
      the ancestors of Ecdyzosoa and of vertebrates. The fact that a majority of
      invertebrates encodes spongin short-chain collagen-related proteins raises the
      important question to the possible function of its members. Considering the
      importance of collagens for animal structure and substratum attachment, both
      families may have played crucial roles in animal diversification.

PMID- 16945980
TI  - Avian influenza virus exhibits rapid evolutionary dynamics.
AB  - Influenza A viruses from wild aquatic birds, their natural reservoir species, are
      thought to have reached a form of stasis, characterized by low rates of
      evolutionary change. We tested this hypothesis by estimating rates of nucleotide
      substitution in a diverse array of avian influenza viruses (AIV) and allowing for
      rate variation among lineages. The rates observed were extremely high, at >10(-3)
      substitutions per site, per year, with little difference among wild and domestic
      host species or viral subtypes and were similar to those seen in mammalian
      influenza A viruses. Influenza A virus therefore exhibits rapid evolutionary
      dynamics across its host range, consistent with a high background mutation rate
      and rapid replication. Using the same approach, we also estimated that the common
      ancestors of the hemagglutinin and neuraminidase sequences of AIV arose within
      the last 3,000 years, with most intrasubtype diversity emerging within the last
      100 years and suggestive of a continual selective turnover.

PMID- 16945981
TI  - The lack of mitochondrial complex I in a CMSII mutant of Nicotiana sylvestris
      increases photorespiration through an increased internal resistance to CO2
      diffusion.
AB  - The cytoplasmic male sterile II (CMSII) mutant lacking complex I of the
      mitochondrial electron transport chain has a lower photosynthetic activity but
      exhibits higher rates of excess electron transport than the wild type (WT) when
      grown at high light intensity. In order to examine the cause of the lower
      photosynthetic activity and to determine whether excess electrons are consumed by
      photorespiration, light, and intercellular CO(2), molar fraction (c(i)) response
      curves of carbon assimilation were measured at varying oxygen molar fractions.
      While oxygen is the major acceptor for excess electrons in CMSII and WT leaves,
      electron flux to photorespiration is favoured in the mutant as compared with the
      WT leaves. Isotopic mass spectrometry measurements showed that leaf internal
      conductance to CO(2) diffusion (g(m)) in mutant leaves was half that of WT
      leaves, thus decreasing the c(c) and favouring photorespiration in the mutant.
      The specificity factor of Rubisco did not differ significantly between both types
      of leaves. Furthermore, carbon assimilation as a function of electrons used for
      carboxylation processes/electrons used for oxygenation processes (J(C)/J(O)) and
      as a function of the calculated chloroplastic CO(2) molar fraction (c(c)) values
      was similar in WT and mutant leaves. Enhanced rates of photorespiration also
      explain the consumption of excess electrons in CMSII plants and agreed with
      potential ATP consumption. Furthermore, the lower initial Rubisco activity in
      CMSII as compared with WT leaves resulted from the lower c(c) in ambient air,
      since initial Rubisco activity on the basis of equal c(c) values was similar in
      WT and mutant leaves. The retarded growth and the lower photosynthetic activity
      of the mutant were largely overcome when plants were grown in high CO(2)
      concentrations, showing that limiting CO(2) supply for photosynthesis was a major
      cause of the lower growth rate and photosynthetic activity in CMSII.

PMID- 16945982
TI  - Risk perceptions and behavioral intentions for Hepatitis B: how do young adults
      fare?
AB  - Young adults are at risk for Hepatitis B infection. Little is known about their
      attitudes and beliefs concerning Hepatitis B, which are determinants of getting
      immunized. This investigation examined risk perceptions and behavioral intentions
      concerning Hepatitis B among a convenience sample of 1070 young adults, 18-24
      years old who participated in a Hepatitis B campaign that aired a prevention
      based advertisement in movies. The campaign did not produce any significant
      effects. Therefore, analyses presented in this paper explored whether risk
      perceptions and intentions vary by sociodemographic characteristics. Most young
      adults do not perceive themselves to be at risk for Hepatitis B, but perceive
      other people to be at risk. Gender and ethnic differences in behavioral
      intentions to seek out Hepatitis B information were also observed. This study
      offers insight about important factors to consider when designing Hepatitis B
      prevention interventions for young adults and suggests that increasing health
      promotion efforts for this group, while accounting for differences in age,
      culture and gender, are warranted.

PMID- 16945983
TI  - Implementation examined in a health center-delivered, educational intervention
      that improved infant growth in Trujillo, Peru: successes and challenges.
AB  - Process evaluation was used to examine the implementation of a randomized,
      controlled trial of an education intervention that improved infant growth in
      Trujillo, Peru. Health personnel delivered the multi-component intervention as
      part of usual care in the government health centers. Quantitative and qualitative
      methods were used to examine process indicators, which included the extent of
      delivery (dose), fidelity to intervention protocol, barriers to implementation
      and context. Results demonstrated that most intervention components were
      delivered at a level of 50-90% of expectations. Fidelity to intervention
      protocol, where measured, was lower (28-70% of expectations). However, when
      compared with existing nutrition education, as represented by the control
      centers, significant improvements were demonstrated. This included both improved
      delivery of existing educational activities as well as delivery of new
      intervention components to strengthen overall nutrition education. Barriers to,
      and facilitators of, implementation were explored with health personnel and
      helped to explain results. This study demonstrates the importance of examining
      actual versus planned implementation in order to improve our understanding of how
      interventions succeed. The information gained from this study will inform future
      evaluation designs, and lead to the development and implementation of more
      effective intervention programs for child health.

PMID- 16945984
TI  - Evaluating the impact of health promotion programs: using the RE-AIM framework to
      form summary measures for decision making involving complex issues.
AB  - Current public health and medical evidence rely heavily on efficacy information
      to make decisions regarding intervention impact. This evidence base could be
      enhanced by research studies that evaluate and report multiple indicators of
      internal and external validity such as Reach, Effectiveness, Adoption,
      Implementation and Maintenance (RE-AIM) as well as their combined impact.
      However, indices that summarize the combined impact of, and complex interactions
      among, intervention outcome dimensions are not currently available. We propose
      and discuss a series of composite metrics that combine two or more RE-AIM
      dimensions, and can be used to estimate overall intervention impact. Although
      speculative and, at this point, there have been limited empirical data on these
      metrics, they extend current methods and are offered to yield more integrated
      composite outcomes relevant to public health. Such approaches offer potential to
      help identify interventions most likely to meaningfully impact population health.

PMID- 16945985
TI  - Stage-specific effects of an action control intervention on dental flossing.
AB  - Health behavior interventions may have different effects when targeting
      individuals at different stages of change. A 'motivation' stage, during which
      intentions are formed, has been distinguished from a 'volition' stage, implying
      that the latter requires self-regulatory effort in implementing and maintaining
      behavior. To test this stage assumption, an action control intervention (self
      monitoring tool for dental flossing) matched to the volition stage and mismatched
      to the motivation stage was provided to 151 university students, with follow-up
      measures of action control and flossing after 2 and 6 weeks. Separate regression
      analyses for motivational and volitional participants indicated that only
      volitional participants benefited from the volitional intervention. This supports
      the usefulness of stage assumptions and the advantage of tailoring interventions
      to participants who reside either in the motivational or in the volitional stage.

PMID- 16945986
TI  - Krachtvoer: process evaluation of a Dutch programme for lower vocational schools
      to promote healthful diet.
AB  - The aim of this study was to examine the fidelity and completeness of the
      implementation of a school-based healthful diet promotion programme called
      'Krachtvoer' (we use the Dutch title of the programme throughout this article. A
      possible translation is Power Food, but this does not reflect the play on words
      in the Dutch title), aimed at lower vocational training students aged 12-14
      years. The teachers' and students' opinions of the programme were also assessed,
      as well as the association between these opinions and the level of
      implementation. Data were collected through structured teachers' monitoring
      reports, in-class observations and in-depth interviews with teachers. Further
      data were drawn from a student questionnaire included in a concurrent cluster
      randomized baseline post-test experimental study evaluating the effects of the
      programme. The present study indicates that the teachers implemented the
      programme largely according to plan, that the teachers appreciated most parts of
      the programme and that the students who were exposed to the programme were more
      appreciative of their nutrition education lessons than students who followed the
      usual curriculum. However, programme elements that teachers did not like were
      often not implemented. We conclude that the Krachtvoer programme is a promising
      tool to encourage students in lower vocational training to adopt diets that are
      more healthful. The present study revealed the stronger and weaker parts of the
      programme and can thus guide programme improvement.

PMID- 16945987
TI  - From science to policy--when are scientific results certain enough?
AB  - The amount of scientific findings linking air pollution with adverse health
      effects is continuously growing and indicates a need for action to improve air
      quality. On 21 September 2005, the European Commission published a new draft
      directive on air quality, as part of the Thematic Strategy on air pollution. This
      is a long-term plan on how to reduce air pollution in the European Union in the
      next 15 years. Immediately after its release, the Commission received criticism
      for not going far enough from various instances, such as research institutions
      and nongovernmental organizations concerned with health and environmental effects
      of air pollution. One policy argument for not taking full measures was the
      argument of scientific uncertainty. In light of this air quality strategy and the
      corresponding criticism which ensued, the present article discusses how the
      ambiguity of scientific uncertainty may contribute to impeding the process of
      translating scientific findings into concrete policy options. As complete
      certainty is likely to never be achieved, the question arises whether it is
      possible to determine and agree on clear and applicable definitions of certain
      levels of scientific certainty. The case referred to in this paper clearly
      demonstrates a situation with discordant views on the uncertainty of scientific
      findings. More discussion on how to define scientific uncertainty and how to deal
      with it would be beneficial for both the scientific and the political
      communities. Finally, it is important to recognize that scientific evidence is
      not the only driver influencing policy decisions.

PMID- 16945988
TI  - Contribution of CYP2C9, CYP2A6, and CYP2B6 to valproic acid metabolism in hepatic
      microsomes from individuals with the CYP2C9*1/*1 genotype.
AB  - The present study investigated the role of specific human cytochrome P450 (CYP)
      enzymes in the in vitro metabolism of valproic acid (VPA) by a complementary
      approach that used individual cDNA-expressed CYP enzymes, chemical inhibitors of
      specific CYP enzymes, CYP-specific inhibitory monoclonal antibodies (MAbs),
      individual human hepatic microsomes, and correlational analysis. cDNA-expressed
      CYP2C9*1, CYP2A6, and CYP2B6 were the most active catalysts of 4-ene-VPA, 4-OH
      VPA, and 5-OH-VPA formation. The extent of 4-OH-VPA and 5-OH-VPA formation by
      CYP1A1, CYP1A2, CYP1B1, CYP2C8, CYP2C19, CYP2D6, CYP2E1, CYP4A11, CYP4F2,
      CYP4F3A, and CYP4F3B was only 1-8% of the levels by CYP2C9*1. CYP2A6 was the most
      active in catalyzing VPA 3-hydroxylation, whereas CYP1A1, CYP2B6, CYP4F2, and
      CYP4F3B were less active. Correlational analyses of VPA metabolism with CYP
      enzyme-selective activities suggested a potential role for hepatic microsomal
      CYP2A6 and CYP2C9. Chemical inhibition experiments with coumarin (CYP2A6
      inhibitor), triethylenethiophosphoramide (CYP2B6 inhibitor), and sulfaphenazole
      (CYP2C9 inhibitor) and immunoinhibition experiments (including combinatorial
      analysis) with MAb-2A6, MAb-2B6, and MAb-2C9 indicated that the CYP2C9 inhibitors
      reduced the formation of 4-ene-VPA, 4-OH-VPA, and 5-OH-VPA by 75-80% in a panel
      of hepatic microsomes from donors with the CYP2C9*1/*1 genotype, whereas the
      CYP2A6 and CYP2B6 inhibitors had a small effect. Only the CYP2A6 inhibitors
      reduced VPA 3-hydroxylation (by approximately 50%). The extent of inhibition
      correlated with the catalytic capacity of these enzymes in each microsome sample.
      Overall, our novel findings indicate that in human hepatic microsomes, CYP2C9*1
      is the predominant catalyst in the formation of 4-ene-VPA, 4-OH-VPA, and 5-OH
      VPA, whereas CYP2A6 contributes partially to 3-OH-VPA formation.

PMID- 16945989
TI  - Gonadotropin-induced apoptosis in human ovarian surface epithelial cells is
      associated with cyclooxygenase-2 up-regulation via the beta-catenin/T-cell factor
      signaling pathway.
AB  - Gonadotropins play a prominent role in ovarian function and pathology. We have
      shown that treatment with gonadotropins (FSH and LH/human chorionic gonadotropin)
      reduces the amount of N-cadherin with a concomitant induction of apoptosis in
      human ovarian surface epithelial (OSE) cells, but precise molecular mechanisms
      remain to be elucidated. Here, we demonstrated activation of beta-catenin/T-cell
      factor (TCF) signaling by gonadotropins. We further showed that ectopic
      expression of N-cadherin was sufficient to recruit beta-catenin to the plasma
      membrane, thereby blocking beta-catenin/TCF-mediated transactivation in
      gonadotropin-treated cells. Transfection with beta-catenin small interfering RNA
      or expression of dominant negative TCF inhibited apoptosis, whereas expression of
      dominant stable beta-catenin (S37A) caused significant apoptosis, thus supporting
      a proapoptotic role for beta-catenin/TCF in human OSE. In addition, we showed
      that gonadotropins enhanced beta-catenin/TCF transcriptional activity through
      inactivation of glycogen synthase kinase-3beta in a phosphatidylinositol 3
      kinase/Akt-dependent manner, indicating cross talk between the
      phosphatidylinositol 3-kinase/Akt and beta-catenin signaling pathways through
      glycogen synthase kinase-3beta. Furthermore, gonadotropins increased
      cyclooxygenase-2 (COX-2) expression via the beta-catenin/TCF pathway. COX-2 also
      played a role in gonadotropin-induced apoptosis, as treatment with the COX-2
      specific inhibitor NS-398 or COX-2 small interfering RNA blocked gonadotropin
      dependent apoptotic activity. These findings suggest that the participation of
      beta-catenin in adhesion and signaling may represent a novel mechanism through
      which gonadotropins may regulate the cellular fate of human OSE.

PMID- 16945990
TI  - Kinase-specific phosphorylation of the estrogen receptor changes receptor
      interactions with ligand, deoxyribonucleic acid, and coregulators associated with
      alterations in estrogen and tamoxifen activity.
AB  - Posttranslational modifications of the estrogen receptor (ER) are emerging as
      important regulatory elements of cross talk between different signaling pathways.
      ER phosphorylation, in particular, has been implicated in the ligand-independent
      effects of ER and in tamoxifen resistance of breast tumors. In our studies,
      Western immunoblot analysis of endogenous ER in parental MCF-7 cells reveals
      specific, ligand-dependent phosphorylations at S118 and S167, with this ligand
      dependence being lost in tamoxifen-resistant, MCF-7 Her2/neu cells. Using highly
      purified components and sensitive fluorescence methods in an in vitro system, we
      show that phosphorylation by different kinases alters ER action through distinct
      mechanisms. Phosphorylation by Src and protein kinase A increases affinity for
      estradiol (E2), whereas ER phosphorylation by MAPK decreases trans
      hydroxytamoxifen (TOT) binding. Affinity of ER for the consensus estrogen
      response element is also altered by phosphorylation in a ligand-specific manner,
      with decrease in affinity of MAPK- and Src-phosphorylated ER in the presence of
      TOT. ER phosphorylation by MAPK, AKT, or protein kinase A increases recruitment
      of steroid receptor coactivator 3 receptor interaction domain to the DNA-bound
      receptor in the presence of E2. Taken together, these results suggest that ER
      phosphorylation alters receptor functions (ligand, DNA, and coactivator binding),
      effecting changes that could lead to an increase in E2 agonism and a decrease in
      TOT antagonistic activity, reflecting changes encountered in tamoxifen resistance
      in endocrine therapy of breast cancer.

PMID- 16945991
TI  - Signaling specificity of interleukin-6 action on glucose and lipid metabolism in
      skeletal muscle.
AB  - We identified signaling pathways by which IL-6 regulates skeletal muscle
      differentiation and metabolism. Primary human skeletal muscle cells were exposed
      to IL-6 (25 ng/ml either acutely or for several days), and small interfering RNA
      gene silencing was applied to measure glucose and fat metabolism. Chronic IL-6
      exposure increased myotube fusion and formation and the mRNA expression of
      glucose transporter 4, peroxisome proliferator activated receptor (PPAR)alpha,
      PPARdelta, PPARgamma, PPARgamma coactivator 1, glycogen synthase, myocyte
      enhancer factor 2D, uncoupling protein 2, fatty acid transporter 4, and IL-6 (P <
      0.05), whereas glucose transporter 1, CCAAT/enhancer-binding protein-alpha, and
      uncoupling protein 3 were decreased. IL-6 increased glucose incorporation into
      glycogen, glucose uptake, lactate production, and fatty acid uptake and
      oxidation, concomitant with increased phosphorylation of AMP-activated protein
      kinase (AMPK), signal transducer and activator of transcription 3, and ERK1/2. IL
      6 also increased phosphatidylinositol (PI) 3-kinase activity (450%; P < 0.05),
      which was blunted by subsequent insulin-stimulation (P < 0.05). IL-6-mediated
      glucose metabolism was suppressed, but lipid metabolism was unaltered, by
      inhibition of PI3-kinase with LY294002. The small interfering RNA-directed
      depletion of AMPK reduced IL-6-mediated fatty acid oxidation and palmitate uptake
      but did not reduce glycogen synthesis. In summary, IL-6 increases glycogen
      synthesis via a PI3-kinase-dependent mechanism and enhances lipid oxidation via
      an AMPK-dependent mechanism in skeletal muscle. Thus, IL-6 directly promotes
      skeletal muscle differentiation and regulates muscle substrate utilization,
      promoting glycogen storage and lipid oxidation.

PMID- 16945993
TI  - Women with left frontal glioblastoma have a significantly shorter survival--why?

PMID- 16945992
TI  - Vitamin D deficiency: prevention or treatment?
AB  - BACKGROUND: Vitamin D deficiency is a chronic condition which contributes to
      general ill health and seems to be re-emerging in our catchment area since
      funding of vitamin D supplementation by Primary Care Trusts ceased. This study
      aims to verify this situation and to assess the cost effectiveness of
      reintroducing vitamin D supplementation in the Burnley Health Care NHS Trust.
      METHODS: Vitamin D deficient patients presenting between January 1994 and May
      2005 were identified and data retrospectively collected from their case notes.
      The cost of treatment and the theoretical cost of primary prevention for the
      Trust population were calculated using previous and current DoH guidelines.
      RESULTS: Fourteen patients were identified, of whom 86% presented in the last 5
      years and 93% were of Asian origin. The incidence of vitamin D deficiency for our
      population is 1 in 923 children overall and 1 in 117 in children of Asian origin.
      The average cost of treatment for each such child is pound2500, while the
      theoretical cost of prevention of vitamin D deficiency in the Asian population
      through primary prevention according to COMA guidance is pound2400 per case.
      CONCLUSIONS: Vitamin D deficiency is re-emerging in our Trust. The overwhelming
      majority of our patients are of Asian origin. The cost of primary prevention for
      this high risk population compares favourably both medically and financially with
      treatment of established disease. We suggest that Primary Care Trusts provide
      funds for vitamin D supplementation of Asian children for at least the first 2
      years of life.

PMID- 16945994
TI  - Abstracts from the Seventh Congress of the European Association for Neuro
      Oncology, Vienna, Austria, September 14-17, 2006.

PMID- 16945996
TI  - Cell culture medium composition and translational adult bone marrow-derived stem
      cell research.
AB  - For most therapeutic strategies using MSC, the preliminary amplification is
      carried out in media containing fetal calf serum (FCS). The theoretical health
      risk of using a xenogenic serum, a recent practice for which we have limited
      data, cannot be underestimated, while amplification using human serum (HS)
      remains controversial. At present, the available information on
      multipotentiality, self-renewal, and transplantability does not permit the
      selection of FCS rather than HS. Cellular modifications observed during cell
      passage seem to indicate a gradual impairment of cells in relation to native MSC,
      suggesting the making of short cell cultures without necessarily trying to
      reinfuse a high number of MSC in patients. With this approach, the volume of HS
      required would remain limited. While clinical studies have already started, many
      problems remain, such as evaluating the quality of the initial mesenchymal
      compartment and the biological properties of the cell suspension with FCS
      compared to those with HS, and depending on culture time.

PMID- 16945995
TI  - Neurosphere assays: growth factors and hormone differences in tumor and nontumor
      studies.
AB  - The "no new neuron" dogma that the brain is quiescent throughout adult life has
      been challenged by the discovery of cells with stem cell-like qualities of self
      renewal and multipotency in the subventricular zone of the lateral ventricles and
      the dentate gyrus of the hippocampus in adults. This self-renewing capacity also
      makes these neural stem cells a possible source of brain tumors, which was
      supported by the discovery of self-sustaining brain tumor stem-like cells in
      cancers such as glioblastoma multiforme. Neurosphere assays are the standard for
      studying these stem-like cells in both normal and cancer tissues. Despite the
      importance of these assays, there is no standardized protocol to allow for a
      comparison of results because several studies use different growth factors and
      hormones at different concentrations. The primary objective of this study is to
      review the literature for both nontumor and tumor studies to assess their
      respective neurosphere assay components. We found significant variation in assay
      components, namely hormones and growth factors, as well as their respective
      concentrations. This illustrates the need for a standardized protocol to allow
      proper comparison among studies and a better assessment of the effects of
      different factors.

PMID- 16945997
TI  - Potential of dental mesenchymal cells in developing teeth.
AB  - The tooth, composed of dentin and enamel, develops through epithelium-mesenchyme
      interactions. Neural crest (NC) cells contribute to the dental mesenchyme in the
      developing tooth and differentiate into dentin-secreting odontoblasts. NC cells
      are known to differentiate into chondrocytes and osteoblasts in the craniofacial
      region. However, it is not clear whether the dental mesenchymal cells in the
      developing tooth possess the potential to differentiate into a lineage(s) other
      than the odontoblast lineage. In this study, we prepared mesenchymal cells from
      E13.5 tooth germ cells and assessed their potential for differentiation in
      culture. They differentiated into odontoblasts, chondrocyte-like cells, and
      osteoblast-like cells. Their derivation was confirmed by tracing NC-derived cells
      as LacZ(+) cells using P0-Cre/Rosa26R mice. Using the flow cytometry-fluorescent
      di-beta-D-galactosidase system, which makes it possible to detect LacZ(+) cells
      as living cells, cell surface molecules of dental mesenchymal cells were
      characterized. Large number of LacZ(+) NC-derived cells expressed platelet
      derived growth factor receptor alpha and integrins. Taken together, these results
      suggest that NC-derived cells with the potential to differentiate into
      chondrocyte-like and osteoblast-like cells are present in the developing tooth,
      and these cells may contribute to tooth organogenesis.

PMID- 16945998
TI  - Isolation and characterization of a stem cell population from adult human liver.
AB  - Several studies suggested the presence of stem cells in the adult normal human
      liver; however, a population with stem cell properties has not yet been isolated.
      The purpose of the present study was to identify and characterize progenitor
      cells in normal adult human liver. By stringent conditions of liver cell
      cultures, we isolated and characterized a population of human liver stem cells
      (HLSCs). HLSCs expressed the mesenchymal stem cell markers CD29, CD73, CD44, and
      CD90 but not the hematopoietic stem cell markers CD34, CD45, CD117, and CD133.
      HLSCs were also positive for vimentin and nestin, a stem cell marker. The absence
      of staining for cytokeratin-19, CD117, and CD34 indicated that HLSCs were not
      oval stem cells. In addition, HLSCs expressed albumin, alpha-fetoprotein, and in
      a small percentage of cells, cytokeratin-8 and cytokeratin-18, indicating a
      partial commitment to hepatic cells. HLSCs differentiated in mature hepatocytes
      when cultured in the presence of hepatocyte growth factor and fibroblast growth
      factor 4, as indicated by the expression of functional cytochrome P450, albumin,
      and urea production. Under this condition, HLSCs downregulated alpha-fetoprotein
      and expressed cytokeratin-8 and cytokeratin-18. HLSCs were also able to undergo
      osteogenic and endothelial differentiation when cultured in the appropriated
      differentiation media, but they did not undergo lipogenic differentiation.
      Moreover, HLSCs differentiated in insulin-producing islet-like structures. In
      vivo, HLSCs contributed to regeneration of the liver parenchyma in severe
      combined immunodeficient mice. In conclusion, we here identified a pluripotent
      progenitor population in adult human liver that could provide a basis for cell
      therapy strategies.

PMID- 16946000
TI  - Plasticity of hepatic cell differentiation: bipotential adult mouse liver clonal
      cell lines competent to differentiate in vitro and in vivo.
AB  - In fetal liver, bipotential hepatoblasts differentiate into hepatocytes and bile
      duct cells (cholangiocytes). The persistence of such progenitor cells in adult
      mouse liver is still debated. In damaged liver of adult murine animals, when
      hepatocyte proliferation is compromised, bipotential oval cells emerge, probably
      from bile ducts, proliferate, and differentiate to regenerate the liver. However,
      treatment to elicit oval cell proliferation is not necessary to obtain
      bipotential stem cells from adult mouse liver. Here, we have isolated bipotential
      clonal cell lines from healthy liver of 8-10-week-old C57BL/6 mice. Primary
      cultures established from hepatocyte-enriched suspensions were characterized by
      time-lapse image acquisition, immunocytology, and RNA transcript analysis.
      Although hepatocytes dedifferentiated with loss of apical polarity and other
      hepatocyte markers, they rapidly activated expression of bile duct/oval cell
      markers. Reversibility of these processes was achieved in part by culture under
      dilute Matrigel or by aging of confluent cultures. Cell lines were obtained at
      high frequency from mass cultures, from isolated colonies, and by primary cloning
      of the hepatocyte-enriched suspension. Cells of the clonal cell lines do not grow
      in soft agar and are nontumorigenic, and they express cytokeratin 19, A6 antigen,
      and alpha6 integrin, as well as a large panel of hepatocyte functions.
      Furthermore, they can participate in liver regeneration in albumin-urokinase-type
      plasminogen activator/severe combined immune-deficient mice, where they
      differentiate in clusters of hepatocytes and occasionally bile ducts. These
      results demonstrate the existence, in normal adult mouse liver, of a significant
      pool of clonogenic cells that are (or can become) bipotential.

PMID- 16945999
TI  - Transforming growth factor-beta1 sensitivity is altered in Abl-Myc- and Raf-Myc
      induced mouse pre-B-cell tumors.
AB  - Understanding the mechanisms leading to transformation of early B-lineage
      precursors is an important step leading to rational design of new treatments for
      precursor (pre)-B-cell leukemia. We used normal mouse pre-B cells to determine if
      and how transforming growth factor (TGF)-beta1 affects these precursors to the B
      cell lineage and whether transformed pre-B cells respond to TGF-beta1. We found
      that normal pre-B cells proliferating in the presence of interleukin (IL)-7 enter
      cell-cycle arrest after exposure to TGF-beta1. However, clonally related IL-7
      independent tumors induced by oncogenes abl + myc or raf + myc have reduced
      sensitivity to TGF-beta1. In contrast, tumor cells induced by myc alone remain
      sensitive to TGF-beta1 growth suppression. These results suggest that lesions in
      different molecular signaling pathways can lead to loss of TGF-beta1 sensitivity
      in a single cell type. The approach of using normal pre-B-cell lines and
      transformation by overexpression of different oncogenes provides a system to
      compare and contrast molecular pathways that lead to full malignancy.

PMID- 16946001
TI  - Ex vivo expansion does not alter the capacity of umbilical cord blood CD34+ cells
      to generate functional T lymphocytes and dendritic cells.
AB  - We examined whether ex vivo expansion of umbilical cord blood progenitor cells
      affected their capacity to generate immune cells such as T lymphocytes (TLs) and
      dendritic cells (DCs). The capacity to generate TLs from cord blood CD34(+) cells
      expanded for 14 days (d14) was compared with that of nonexpanded CD34(+) cells
      (d0) using fetal thymus organ cultures or transfer into nonobese diabetic/severe
      combined immunodeficient mice. The cell preparations yielded comparable
      percentages of immature (CD4(+)CD8(-), CD4(+)CD8(+)) TLs and functional mature
      (CD3(+)CD4(+), CD3(+)CD8(+)) TLs with an analogous TCR (T-cell receptor)-Vbeta
      repertoire pattern. As regards DCs, d0 and d14 CD34(+) cells also yielded similar
      percentages of CD1a(+) DCs with the same expression levels of HLA-DR,
      costimulatory and adhesion molecules, and chemokine receptors. DCs derived from
      either d14 or d0 CD34(+) stimulated allogeneic TLs to the same extent, and the
      cytokine pattern production of these allogeneic TLs was similar with no shift
      toward a predominant Th1 or Th2 response. Even though the intrinsic capacity of
      d14 CD34(+) cells to generate DCs was 13-fold lower than that of d0 CD34(+)
      cells, this reduction was offset by the prior amplification of the CD34(+) cells,
      resulting in the overall production of 15-fold more DCs. These data indicate that
      ex vivo expansion of CD34(+) cells does not impair T lymphopoiesis nor DC
      differentiation capacity.

PMID- 16946003
TI  - The paired box-8/peroxisome proliferator-activated receptor-gamma oncogene in
      thyroid tumorigenesis.
AB  - The American Cancer Society estimates 30,180 new cases of thyroid cancer in the
      United States in 2006. Of all thyroid cancers, 15-20% are follicular thyroid
      carcinoma (FTC), making this the second most common thyroid malignancy (after
      papillary carcinoma). A proportion of FTC has been found to be associated with a
      chromosomal translocation, t (2, 3)(q13;p25), which fuses the thyroid-specific
      transcription factor paired box-8 with the peroxisome proliferator-activated
      receptor-gamma nuclear receptor, a ubiquitously expressed transcription factor.
      This fusion event causes expression of a paired box-8/peroxisome proliferator
      activated receptor-gamma fusion protein (PPFP). PPFP is detected in approximately
      30% of FTC. In this report we review data on the role of PPFP in FTC, its
      mechanism of oncogenesis, and PPFP targeting as a strategy in thyroid cancer
      treatment.

PMID- 16946002
TI  - Pregnancy-associated plasma protein-A increases osteoblast proliferation in vitro
      and bone formation in vivo.
AB  - Pregnancy-associated plasma protein (PAPP)-A, a protease for IGF binding protein
      (IGFBP)-2, -4, and -5, may enhance IGF action by increasing its bioavailability.
      Here we have determined the role and mechanism of action of PAPP-A in the
      regulation of osteoblast proliferation in vitro and bone metabolism in vivo.
      Recombinant PAPP-A (100 ng/ml) significantly increased osteoblast proliferation
      and free IGF-I concentration. These effects were abolished by noncleavable IGFBP
      4, suggesting that PAPP-A promotes osteoblast proliferation by increasing IGF
      bioavailability. To determine whether PAPP-A exerts an anabolic effect on bone in
      vivo, we developed transgenic mice that overexpress PAPP-A in osteoblasts using
      the 2.3-kb rat type I collagen promoter. Consistent with the increase in IGFBP-4
      proteolysis, free IGF-I concentration was significantly increased in the
      conditioned medium of cultured osteoblasts derived from transgenic mice compared
      with the wild-type littermates. Calvarial bone thickness, bone marrow cavity, and
      skull bone mineral density were significantly increased in transgenic mice. Bone
      size-related parameters in femur and tibia such as total bone area and periosteal
      circumference as determined by peripheral quantitated computed tomography and
      histological analysis were significantly increased in transgenic mice. Bone
      formation rate and osteoid surface were increased by more than 2-fold, whereas
      bone resorbing surface was unaffected. These anabolic effects were sustained with
      aging. These findings provide strong evidence that PAPP-A acts as a potent
      anabolic factor in the regulation of bone formation. Thus, enhancing IGF
      bioavailability by PAPP-A can be a powerful strategy in the treatment of certain
      metabolic diseases such as osteoporosis.

PMID- 16946004
TI  - Tumor necrosis factor-alpha activates transcription of inducible repressor form
      of 3',5'-cyclic adenosine 5'-monophosphate-responsive element binding modulator
      and represses P450 aromatase and inhibin alpha-subunit expression in rat ovarian
      granulosa cells by a p44/42 mitogen-activated protein kinase-dependent mechanism.
AB  - The proinflammatory cytokine TNFalpha has important actions at the level of the
      ovary, including inhibition of P450 aromatase (P450AROM) activity and the
      secretion of inhibin, two proteins that are markers of the granulosa cell's
      differentiated status. Because the transcription of both P450AROM and inhibin
      alpha-subunit can be suppressed in the ovary by the inducible repressor isoform
      of cAMP-responsive element binding modulator (ICER), we have investigated whether
      TNFalpha and its intracellular messenger ceramide can induce ICER expression and
      the mechanisms whereby the induction is accomplished. ICER mRNA levels were
      assessed by RT-PCR in granulosa cells treated with TNFalpha, the ceramide
      mobilizing enzyme sphingomyelinase (SMase), or C6-cer, a cell-permeant ceramide
      analog. Rapid (3 h) yet transient increases in the four isoforms of ICER were
      observed in response to all treatments. Likewise, ICER protein measured by
      immunoprecipitation with a specific antibody increases after TNFalpha, SMase, or
      C6-cer treatment. The mandatory phosphorylation of cAMP-responsive element
      binding was also observed in response to TNFalpha, SMase, or C6-cer and shown to
      be prevented by the p44/42 MAPK-specific inhibitor PD098059 but no other kinase
      blockers. Activation of p44/42 MAPK by the cytokine and its messenger was
      subsequently demonstrated as well as the inhibition of ICER expression by
      PD098059. Finally, the blocking of p44/42 MAPK activation prevented TNFalpha
      inhibition of FSH-dependent increases in P450AROM and inhibin alpha-subunit mRNA
      levels, thus indicating that p44/42 MAPK-mediated ICER expression may be
      accountable for the effects of TNFalpha on the expression of both proteins.

PMID- 16946005
TI  - Estradiol inhibition of voltage-activated and gonadotropin-releasing hormone
      induced currents in mouse gonadotrophs.
AB  - We report the first study of voltage-activated and GnRH-induced plasma membrane
      currents and their modulation by estradiol (E2) in mouse gonadotrophs. In
      consideration of the pleiotropic effects of E2 on gonadotrophin secretion and the
      relationship between plasma membrane electrical excitability and secretion, our
      objective was to determine the role of E2 in modulating gonadotroph plasma
      membrane currents. We measured total voltage-activated and GnRH-induced currents
      using the perforated-patch configuration of the patch-clamp technique, which
      preserves signaling pathways, including GnRH-induced Ca2+ oscillations. We show
      that female mouse gonadotrophs are similar to those from other species in that
      the voltage-activated net current response exhibits an inward fast activating
      current that is inhibited by tetrodotoxin, which is characteristic of a Na+
      current, and a larger magnitude outward current with a profile suggesting the
      presence of multiple K+ currents. Furthermore, in voltage-clamped mouse
      gonadotrophs, GnRH activates large amplitude current oscillations that are apamin
      sensitive and have a reversal potential of -90 mV, consistent with Ca2+-activated
      K+ currents. Significantly, E2 pretreatment for 2-5 d decreased the density of
      both the peak outward voltage-activated current and the peak GnRH-induced
      current. The specific linkage between the observed E2 effects on membrane
      currents and, ultimately, gonadotroph function remains to be established.
      However, because decreased K+ current density is associated with an increase in
      membrane electrical excitability, we postulate increased excitability is one of
      the modes of action of E2 in sensitizing the gonadotroph to GnRH, an event
      central to the regulation of cyclic gonadotrophin secretion.

PMID- 16946007
TI  - Minireview: vitamin D receptor: new assignments for an already busy receptor.
AB  - With its discovery in 1920, the molecule vitamin D achieved prominence as a
      nutritionally essential vitamin important for calcium homeostasis, particularly
      in the intestine and bone. Then in 1932, the elucidation of vitamin D's chemical
      structure revealed that this vitamin was in fact a steroid. But it was not until
      the late 1960s that it was appreciated that the steroid vitamin D was a precursor
      of a new steroid hormone, 1alpha,25(OH)2-vitamin D3 [1alpha,25(OH)2D3], that is
      produced by the kidney acting as an endocrine gland. The discovery in 1969 of the
      nuclear vitamin D receptor (VDR) for 1alpha,25(OH)2D3 initiated a two-decade-long
      proliferation of reports that collectively described the broad sphere of
      influence of the vitamin D endocrine system that is defined by the presence of
      the VDR in over 30 tissue/organs of man. The new genomic frontiers defined by the
      cellular presence of the VDR include the immune system's B and T lymphocytes,
      hair follicle, muscle, adipose tissue, bone marrow, and cancer cells.
      Unexpectedly in the mid 1980s, a new world of 1alpha,25(OH)2D3-mediated rapid
      responses (RR) was discovered. These were responses that occurred too rapidly
      (minutes to an hour) to be explained as the simple consequence of the nuclear VDR
      regulating gene transcription. Some RR examples include the rapid intestinal
      absorption of calcium (transcaltachia), secretion of insulin by pancreatic beta
      cells, opening of voltage-gated Ca2+ and Cl- channels in osteoblasts, and the
      rapid migration of endothelial cells. The question then arose as to whether there
      was a second receptor, apart from the nuclear VDR, which responded to the
      presence of 1alpha,25(OH)2D3 to generate RR? After some false starts, it now
      appears that the classic VDR, long known to reside in the cell nucleus, in some
      cells is also associated with caveolae present in the plasma membrane.
      Furthermore, the chemical properties of the conformationally flexible
      1alpha,25(OH)2D3 allow it to generate different shaped ligands for the VDR that
      are selective either for genomic or for RR. This minireview summarizes a proposed
      conformational ensemble model of the VDR that provides insight into how different
      ligand shapes of 1alpha,25(OH)2D3 acting through the VDR in different cellular
      locations can selectively mediate both genomic and RR.

PMID- 16946008
TI  - AKT in thyroid tumorigenesis and progression.
AB  - AKT (protein kinase B) is a central signaling molecule in the phosphatidyl
      inositol 3-kinase pathway that is frequently activated in human cancer. AKT
      activation regulates energy metabolism, apoptosis, proliferation, and migration
      in many cell systems. In thyroid cancer, AKT activation is involved in
      tumorigenesis, particularly in both inherited and sporadic forms of follicular
      thyroid cancer. Phosphatidyl inositol 3-kinase and AKT signaling also appear to
      play an important role in progression of both papillary and follicular cancers.
      In this review, the role of AKT in thyroid cancer development and progression are
      discussed with a focus on areas of current debate in the literature.

PMID- 16946006
TI  - Minireview: rapid glucocorticoid signaling via membrane-associated receptors.
AB  - Glucocorticoids are secreted into the systemic circulation from the adrenal
      cortex and initiate a broad range of actions throughout the organism that
      regulate the function of multiple organ systems, including the liver, muscle, the
      immune system, the pancreas, fat tissue, and the brain. Delayed glucocorticoid
      effects are mediated by classical steroid mechanisms involving transcriptional
      regulation. Relatively rapid effects of glucocorticoids also occur that are
      incompatible with genomic regulation and invoke a noncanonical mode of steroid
      action. Studies conducted in several labs and on different species suggest that
      the rapid effects of glucocorticoids are mediated by the activation of one or
      more membrane-associated receptors. Here, we provide a brief review focused on
      multiple lines of evidence suggesting that rapid glucocorticoid actions are
      triggered by, or at least dependent on, membrane-associated G protein-coupled
      receptors and activation of downstream signaling cascades. We also discuss the
      possibility that membrane-initiated actions of glucocorticoids may provide an
      additional mechanism for the regulation of gene transcription.

PMID- 16946009
TI  - Gene methylation in thyroid tumorigenesis.
AB  - Aberrant gene methylation plays an important role in human tumorigenesis,
      including thyroid tumorigenesis. Many tumor suppressor genes are aberrantly
      methylated in thyroid cancer, and some even in benign thyroid tumors, suggesting
      a role of this epigenetic event in early thyroid tumorigenesis. Methylation of
      some of these genes tends to occur in certain types of thyroid cancer and is
      related to specific signaling pathways. For example, methylation of PTEN and
      RASSF1A genes occurs mostly in follicular thyroid cancer, and its tumorigenic
      role may be related to the phosphatidylinositol 3-kinase/Akt signaling pathway,
      whereas methylation of genes for tissue inhibitor of metalloproteinase-3, SLC5A8,
      and death-associated protein kinase occurs in papillary thyroid cancer and is
      related to the BRAF/MAPK kinase/MAPK pathway. Methylation of thyroid-specific
      genes, such as those for sodium/iodide symporter and thyroid-stimulating hormone
      receptor, is also common in thyroid cancer. Although its tumorigenic role is not
      clear, methylation, and hence silencing, of these thyroid-specific genes is a
      cause for the failure of clinical radioiodine treatment of thyroid cancer. Unlike
      gene methylation, histone modifications have been relatively poorly investigated
      in thyroid tumors. Future studies need to emphasize the mechanistic aspects of
      these two types of epigenetic alterations to uncover new molecular mechanisms in
      thyroid tumorigenesis and to provide novel therapeutic targets for thyroid
      cancer.

PMID- 16946010
TI  - RET/PTC rearrangements and BRAF mutations in thyroid tumorigenesis.
AB  - Thyroid papillary carcinoma is the most common type of endocrine cancer. It is
      frequently associated with genetic alterations leading to activation of the MAPK
      signaling pathway. The two most frequently affected genes, BRAF and RET, are
      activated by either point mutation or as a result of chromosomal rearrangement.
      These mutations are tumorigenic in thyroid follicular cells and correlate with
      specific phonotypical features and biological properties of papillary carcinomas,
      including tumor aggressiveness and response to radioiodine therapy. Molecular
      inhibitors that block RET/PTC or BRAF kinase activity have shown substantial
      therapeutic effects in the experimental systems and are currently being tested in
      clinical trials.

PMID- 16946011
TI  - Gene expression profiling of human endometrial-trophoblast interaction in a
      coculture model.
AB  - Investigating the interaction of human endometrium and trophoblast during
      implantation is difficult in vitro and impossible in vivo. This study was
      designed to analyze the effect of trophoblast on endometrial stromal cells during
      implantation by comprehensive gene profiling. An in vitro coculture system of
      endometrial stromal cells with first-trimester trophoblast explants was
      established. Trophoblast and endometrial stromal cells were separated after 24 h.
      Gene expression of endometrial stromal cells after coculture was compared with
      the gene expression of endometrial stromal cells cultured alone by microarray
      analysis. We confirmed the expression of distinct genes using real-time PCR.
      Genes up-regulated included those for inflammatory response, immune response, and
      chemotaxis (pentraxin-related gene 3, chemokine ligands, IL-8, IL-1 receptors, IL
      18 receptor, IL-15, IL-15 receptor, TNF-alpha-induced protein 6, and IL-6 signal
      transducer), regulators of cell growth (IGF-binding proteins 1 and 2) and signal
      transduction. Also up-regulated were genes for growth and development, glucose
      metabolism, and lipid metabolism: DKK-1, WISP, IGF-II, hydroxysteroid 11beta
      dehydrogenase 1, hydroxyprostaglandin dehydrogenase 15, prostaglandin E synthase,
      prostaglandin F receptor, aldehyde dehydrogenase 1 family, member A3 and
      phosphatidic acid phosphatase type 2B. Other genes included genes for cell-cell
      signaling (pre-B-cell colony-enhancing factor 1), proteolysis, calcium ion
      binding, regulation of transcription, and others. Down-regulated genes included
      genes for proteolysis (MMP-11 and mitochondrial intermediate peptidase), genes
      for cell death (caspase 6, death-associated protein kinase 1, and histone
      deacetylase 5), transcription factors (sex determining region Y-box 4, dachshund
      homolog 1, ets variant gene 1, and zinc finger protein 84 and 435), and genes for
      humoral immune response (CD24 antigen). Trophoblast has a significant impact on
      endometrial stromal cell gene expression. Some of the genes regulated by
      trophoblast in endometrial stromal cells are already known to be regulated by
      progesterone and show the endocrine function of trophoblast during pregnancy.
      Others are genes so far unknown to play a role in endometrial-trophoblast
      interaction and open a wide field of investigation.

PMID- 16946012
TI  - Minireview: aldosterone and the cardiovascular system: genomic and nongenomic
      effects.
AB  - There is clear evidence for rapid nongenomic effects of aldosterone in the
      cardiovascular system in addition to its well characterized effects of
      unidirectional transepithelial sodium transport. Many of these effects are
      mediated by the classical mineralocorticoid receptors, although others may be
      exerted independently. Given that mineralocorticoid receptors are largely
      constitutively occupied but not activated by physiological glucocorticoids,
      effects of aldosterone administered in vitro or in vivo may or may not equate
      with true physiological mineralocorticoid roles. In many systems (e.g. blood
      pressure regulation and cardiac fibrosis), the time course of effects is such
      that it is not possible, and perhaps not important, to distinguish between rapid
      nongenomic and classical genomic effects in the context of homeostatic
      physiology.

PMID- 16946013
TI  - Developmental programming: differential effects of prenatal exposure to bisphenol
      A or methoxychlor on reproductive function.
AB  - Increased occurrence of reproductive disorders has raised concerns regarding the
      impact of endocrine-disrupting chemicals on reproductive health, especially when
      such exposure occurs during fetal life. Prenatal testosterone (T) treatment leads
      to growth retardation, postnatal hypergonadotropism, compromised estradiol
      positive feedback, polycystic ovaries, and infertility in the adult. Prenatal
      dihydrotestosterone treatment failed to affect ovarian morphology or estradiol
      positive feedback, suggesting that effects of prenatal T may be facilitated via
      conversion of T to estradiol, thus raising concerns regarding fetal exposure to
      estrogenic endocrine-disrupting chemicals. This study tested whether fetal
      exposure to methoxychlor (MXC) or bisphenol A (BPA) would disrupt cyclicity in
      the ewe. Suffolk ewes were administered MXC (n=10), BPA (n=10) (5 mg/kg.d sc in
      cotton seed oil) or the vehicle (C; n=16) from d 30 to 90 of gestation. On d 60
      of treatment, maternal MXC concentrations in fat tissue and BPA in blood averaged
      approximately 200 microg/g fat and 37.4+/-3.3 ng/ml, respectively. Birth weights
      of BPA offspring were lower (P<0.05) relative to C. There was no difference in
      the time of puberty between groups. BPA females were hypergonadotropic during
      early postnatal life and ended their breeding season later, compared with C.
      Characterization of cyclic changes after synchronization with prostaglandin
      F2alpha in five C, six MXC, and six BPA females found that the onset of the LH
      surge was delayed in MXC (P<0.05) and the LH surge magnitude severely dampened
      (P<0.05) in BPA sheep. These findings suggest that prenatal BPA and MXC exposure
      have long-term differential effects on a variety of reproductive endocrine
      parameters that could impact fertility.

PMID- 16946014
TI  - Androgens differentially potentiate mouse intestinal smooth muscle by nongenomic
      activation of polyamine synthesis and Rho kinase activation.
AB  - We demonstrate that testosterone and its active metabolite 5alpha
      dihydrotestosterone acutely (approximately 30 min) potentiate mouse ileal, but
      not duodenal, muscle activity. Androgens augment the amplitude of spontaneous
      peak-to-peak oscillations, alter the spontaneous activity frequency spectrum, and
      increase the amplitude of calcium-induced and carbachol-induced contractions.
      Concentration-dependence analyses revealed that maximal potentiation (449-910%)
      occurred at physiological concentrations of androgens (100 pM to 10 nM) with EC50
      values in the picomolar range (8-20 pM). Western blot analyses using an
      antiandrogen receptor (anti-AR) antibody revealed the presence of two different
      AR proteins migrating at 87 and 110 kDa in ileal, but not duodenal, extracts.
      Androgen-induced potentiation was prevented by preincubation with AR antagonists
      flutamide or cyproterone acetate but was unaffected by pretreatment with
      cycloheximide plus actinomycin D, indicating that potentiation was mediated by
      ARs via a novel nongenomic mechanism. Androgen effects were mimicked by
      polyamines putrescine and spermine and were blocked by the ornithine
      decarboxylase and S-adenosyl-L-methionine decarboxylase inhibitors alpha
      difluoromethylornithine and berenil, respectively. Accordingly, androgens
      increase alpha-difluoromethylornithine-sensitive ornithine-decarboxylase-
      mediated L-ornithine decarboxylation in ileal tissues within the same time course
      as isometric potentiation. Both putrescine and dihydrotestosterone induced Ca2+
      sensitization of ionomycin-permeabilized ileal smooth muscle. Finally, inhibition
      of the Rho kinase (ROK) pathway with the specific inhibitor Y27632 completely
      prevented androgen-induced potentiation. In agreement, androgens elicited ROK
      induced Ser19 phosphorylation of myosin light chain 2 in ileal muscle. These data
      indicate that androgens potentiate ileal contractile activity by an AR-dependent
      nongenomic mechanism involving intracellular polyamine signaling and Ca2+
      sensitization via ROK activation.

PMID- 16946015
TI  - Minireview: estrogen receptor-mediated rapid signaling.
AB  - In addition to nuclear-initiated (genomic) responses, estrogen receptors (ERs)
      have the ability to facilitate rapid, membrane-initiated, estrogen-triggered
      signaling cascades via a plasma membrane-associated form of the receptor. These
      rapid responses are dependent on assembly of membrane ER-centered multimolecular
      complexes, which can transduce ligand-activated signals to affect a variety of
      enzymatic pathways, often occurring in a cell-type-specific fashion with tissue
      specific physiological outcomes. In some instances, cross-talk occurs between
      these membrane-initiated and nuclear responses, ultimately regulating
      transcriptional activation. The role of splice variants in membrane-initiated
      estrogen responses has been described, notably those within the vascular
      endothelium. In this review, we describe the evidence for membrane ERs, the
      molecular components of the aforementioned signaling complexes and pathways, the
      relevance of ER splice variants, and ER-mediated responses in specific tissues.
      Our growing understanding of ER-mediated actions at a molecular level will
      provide insight into the controversies surrounding hormone replacement therapy in
      postmenopausal women.

PMID- 16946017
TI  - Communicable disease and health protection quarterly review: January to March
      2006. From the Health Protection Agency, Centre for Infections.

PMID- 16946016
TI  - Fanconi anemia A is a nucleocytoplasmic shuttling molecule required for
      gonadotropin-releasing hormone (GnRH) transduction of the GnRH receptor.
AB  - GnRH binds its cognate G protein-coupled GnRH receptor (GnRHR) located on
      pituitary gonadotropes and drives expression of gonadotropin hormones. There are
      two gonadotropin hormones, comprised of a common alpha- and hormone-specific beta
      subunit, which are required for gonadal function. Recently we identified that
      Fanconi anemia a (Fanca), a DNA damage repair gene, is differentially expressed
      within the LbetaT2 gonadotrope cell line in response to stimulation with GnRH.
      FANCA is mutated in more than 60% of cases of Fanconi anemia (FA), a rare
      genetically heterogeneous autosomal recessive disorder characterized by bone
      marrow failure, endocrine tissue cancer susceptibility, and infertility. Here we
      show that induction of FANCA protein is mediated by the GnRHR and that the
      protein constitutively adopts a nucleocytoplasmic intracellular distribution
      pattern. Using inhibitors to block nuclear import and export and a GnRHR
      antagonist, we demonstrated that GnRH induces nuclear accumulation of FANCA and
      green fluorescent protein (GFP)-FANCA before exporting back to the cytoplasm
      using the nuclear export receptor CRM1. Using FANCA point mutations that locate
      GFP-FANCA to the cytoplasm (H1110P) or functionally uncouple GFP-FANCA (Q1128E)
      from the wild-type nucleocytoplasmic distribution pattern, we demonstrated that
      wild-type FANCA was required for GnRH-induced activation of gonadotrope cell
      markers. Cotransfection of H1110P and Q1128E blocked GnRH activation of the
      alphaGsu and GnRHR but not the beta-subunit gene promoters. We conclude that
      nucleocytoplasmic shuttling of FANCA is required for GnRH transduction of the
      alphaGSU and GnRHR gene promoters and propose that FANCA functions as a GnRH
      induced signal transducer.

PMID- 16946018
TI  - MD-2 expression is not required for cell surface targeting of Toll-like receptor
      4 (TLR4).
AB  - The cell surface receptor complex formed by TLR4 and myeloid differentiation 2
      (MD-2) is engaged when cells are exposed to LPS. Recent studies suggested that
      surface localization of functional mouse TLR4 (mTLR4) depends on the simultaneous
      expression of MD-2. As we did not observe a similar requirement, we conducted a
      comparative study of human TLR4 and mTLR4 surface expression in immune cells
      derived from the MD-2 knockout mouse and LPS-responsive cell lines and in cells
      that ectopically express TLR4. Our results indicate that in the human and mouse
      models, neither TLR4 function nor TLR4 surface targeting requires MD-2
      coexpression. Accordingly, we report on one human cell line, which constitutively
      expresses functional TLR4 on the cell surface in the absence of MD-2 expression.

PMID- 16946019
TI  - The role of cytokines in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a frequent malignancy worldwide with a high
      rate of metastasis. The hepatitis B and C viruses are considered major
      etiological factors associated with the development of HCC, particularly as a
      result of their induction of chronic inflammation. There is increasing evidence
      that the inflammatory process is inherently associated with many different cancer
      types, including HCC. Specifically, this review aims to cover evidence for the
      potential roles of cytokines, an important component of the immune system, in
      promoting HCC carcinogenesis and progression. A global summary of cytokine
      levels, functions, polymorphisms, and therapies with regard to HCC is presented.
      In particular, the role of proinflammatory Th1 and anti-inflammatory Th2 cytokine
      imbalances in the microenvironment of HCC patients with metastasis and the
      possible clinical significance of these findings are addressed. Overall, multiple
      studies, spanning many decades, have begun to elucidate the important role of
      cytokines in HCC.

PMID- 16946020
TI  - Monocyte-derived macrophages and myeloid cell lines as targets of HIV-1
      replication and persistence.
AB  - HIV infection of mononuclear phagocytes (MP), mostly as tissue macrophages, is a
      dominant feature in the pathogenesis of HIV disease and its progression to AIDS.
      Although the general mechanism of infection is not dissimilar to that of CD4+ T
      lymphocytes occurring via interaction of the viral envelope with CD4 and a
      chemokine receptor (usually CCR5), other features are peculiar to MP infection.
      Among others, the long-term persistence of productive infection, sustained by the
      absence of substantial cell death, and the capacity of the virions to bud and
      accumulate in intracellular multivesicular bodies (MVB), has conferred to MP the
      role of "Trojan horses" perpetuating the chronic state of infection. Because the
      investigation of tissue macrophages is often very difficult for both ethical and
      practical reasons of accessibility, most studies of in vitro infection rely upon
      monocyte-derived macrophages (MDM), a methodology hampered by inter-patient
      variability and lack of uniformity of experimental protocols. A number of cell
      lines, mostly Mono Mac, THP-1, U937, HL-60, and their derivative chronically
      infected counterparts (such as U1 and OM-10.1 cell lines) have complemented the
      MDM system of infection providing useful information on the features of HIV
      replication in MP. This article describes and compares the most salient features
      of these different cellular models of MP infection by HIV.

PMID- 16946021
TI  - Changing times: a longitudinal analysis of international firearm suicide data.
AB  - We investigated changes in the proportion of firearm suicides in Western
      countries since the 1980s and the relation of these changes to the change in the
      proportion of households owning firearms. Several countries had an obvious
      decline in firearm suicides: Norway, United Kingdom, Canada, Australia, and New
      Zealand. Multilevel modeling of longitudinal data confirmed the effect of the
      proportion of households owning firearms. Legislation and regulatory measures
      reducing the availability of firearms in private households can distinctly
      strengthen the prevention of firearm suicides.

PMID- 16946022
TI  - Residual force enhancement after lengthening is present during submaximal plantar
      flexion and dorsiflexion actions in humans.
AB  - Stretch of an activated muscle causes a transient increase in force during the
      stretch and a sustained, residual force enhancement (RFE) after the stretch. The
      purpose of this study was to determine whether RFE is present in human muscles
      under physiologically relevant conditions (i.e., when stretches were applied
      within the working range of large postural leg muscles and under submaximal
      voluntary activation). Submaximal voluntary plantar flexion (PF(v)) and
      dorsiflexion (DF(v)) activation was maintained by providing direct visual
      feedback of the EMG from soleus or tibialis anterior, respectively. RFE was also
      examined during electrical stimulation of the plantar flexion muscles (PF(s)).
      Constant-velocity stretches (15 degrees /s) were applied through a range of
      motion of 15 degrees using a custom-built ankle torque motor. The muscles
      remained active throughout the stretch and for at least 10 s after the stretch.
      In all three activation conditions, the stable joint torque measured 9-10 s after
      the stretch was greater than the isometric joint torque at the final joint angle.
      When expressed as a percentage of the isometric torque, RFE values were 7, 13,
      and 12% for PF(v), PF(s), DF(v), respectively. These findings indicate that RFE
      is a characteristic of human skeletal muscle and can be observed during
      submaximal (25%) voluntary activation when stretches are applied on the ascending
      limb of the force-length curve. Although the underlying mechanisms are unclear,
      it appears that sarcomere popping and passive force enhancement are insufficient
      to explain the presence of RFE in these experiments.

PMID- 16946023
TI  - Age-dependent changes of airway and lung parenchyma in C57BL/6J mice.
AB  - In the current study, we hypothesize that senescent-dependent changes between
      airway and lung parenchymal tissues of C57BL/6J (B6) mice are not synchronized
      with respect to altered lung mechanics. Furthermore, aging modifications in
      elastin fiber and collagen content of the airways and lung parenchyma are
      remodeling events that differ with time. To test these hypotheses, we performed
      quasi-static pressure-volume (PV) curves and impedance measurements of the
      respiratory system in 2-, 20-, and 26-mo-old B6 mice. From the PV curves, the
      lung volume at 30 cmH(2)O pressure (V(30)) and respiratory system compliance
      (Crs) were significantly (P < 0.01) increased between 2 and 20 mo of age,
      representing about 80-84% of the total increase that occurred between 2 and 26 mo
      of age. Senescent-dependent changes in tissue damping and tissue elastance were
      analogous to changes in V(30) and Crs; that is, a majority of the parenchymal
      alterations in the lung mechanics occurred between 2 and 20 mo of age. In
      contrast, significant decreases in airway resistance (R) occurred between 20 and
      26 mo of age; that is, the decrease in R between 2 and 20 mo of age represented
      only 29% (P > 0.05) of total decrease occurring through 26 mo. Morphometric
      analysis of the elastic fiber content in lung parenchyma was significantly (P <
      0.01) decreased between 2 and 20 mo of age. To the contrary, increased collagen
      content was significantly delayed until 26 mo of age (P < 0.01, 2 vs. 26 mo). In
      conclusion, our data demonstrate that senescent-dependent changes in airway and
      lung tissue mechanics are not synchronized in B6 mice. Moreover, the reduction in
      elastic fiber content with age is an early lung remodeling event, and the
      increased collagen content in the lung parenchyma occurs later in senescence.

PMID- 16946024
TI  - Stretching human muscles makes them stronger.

PMID- 16946025
TI  - Continuous cardiac output monitoring by blood pressure analysis.

PMID- 16946026
TI  - Mechanisms underlying myogenesis: complex and likely to become more so!

PMID- 16946027
TI  - Impaired flow-mediated dilation with age is not explained by L-arginine
      bioavailability or endothelial asymmetric dimethylarginine protein expression.
AB  - Aging is associated with a decline in vascular endothelial function, manifesting
      in part as impaired flow-mediated arterial dilation (FMD), but the underlying
      mechanisms are uncertain. Impaired FMD may be mediated in part by a decrease in
      synthesis of nitric oxide by endothelial nitric oxide synthase, and in clinical
      populations this has been attributed to competitive inhibition of l-arginine
      binding sites by asymmetric dimethylarginine (ADMA). If this mechanism is
      involved in the age-associated decline in FMD, increasing l-arginine
      concentration may swing the competitive balance in favor of l-arginine binding,
      restoring nitric oxide synthesis, and enhancing FMD in older humans. To test this
      hypothesis, we measured FMD (brachial ultrasound) in 10 younger (21 +/- 1 yr) and
      12 older healthy men and women (60 +/- 2 yr) following infusion of vehicle or
      vehicle + l-arginine. Baseline FMD in the older subjects was only approximately
      60% of that in the younger subjects (P = 0.002). l-Arginine did not significantly
      increase FMD in either group despite 23-fold (older) and 19-fold (younger)
      increases in plasma l-arginine concentrations (P < 0.0001 vs. control). Protein
      expression (immunofluorescence) in vascular endothelial cells showed that ADMA
      and the enzyme isoform that controls its degradation, dimethylarginine
      dimethylaminohydrolase II, were not different in the younger and older subjects.
      Endothelium-independent vasodilation (sublingual nitroglycerine) was not
      different between age groups or conditions. We conclude that acutely increasing
      plasma concentrations of l-arginine do not significantly improve brachial artery
      FMD in healthy older subjects and thus does not restore the age-associated loss
      of FMD. Together with the finding that endothelial cell ADMA protein expression
      was not increased in older adults, these findings suggest that competitive
      inhibition of l-arginine binding sites on endothelial nitric oxide synthase by
      ADMA is not an important mechanism contributing to impaired conduit artery
      endothelium-dependent dilation with aging in healthy humans.

PMID- 16946029
TI  - Influences of adenosine receptor antagonism on vasodilator responses to adenosine
      and exercise in adenosine responders and nonresponders.
AB  - We previously demonstrated a bimodal distribution of vasodilator responsiveness
      to adenosine (Ado) infusion in human subjects, despite similar responses to
      exercise between subgroups [subjects responsive to Ado infusion (Ado responders)
      and subjects with blunted vasodilator responses to Ado infusion (Ado
      nonresponders]). (Martin EA, Nicholson WT, Eisenach JH, Charkoudian N, and Joyner
      MJ. J Appl Physiol 101: 492-499, 2006). A component of this difference was
      attributed to a larger nitric oxide component of Ado-mediated vasodilation in
      responders. However, there may also be differences in Ado receptors between these
      subgroups. We hypothesized that Ado receptor antagonism would reduce vasodilator
      responsiveness to Ado and exercise only in Ado responders. To test this
      hypothesis, we compared forearm vasodilation induced by intra-arterial infusion
      of three doses of Ado to vasodilation during three workloads of forearm handgrip
      exercise before and after Ado receptor antagonism with aminophylline (Aph) in 19
      subjects. In Ado responders, the change in forearm vascular conductance above
      baseline for the low, medium, and high doses of Ado, respectively, was 93 +/- 16,
      140 +/- 14, 194 +/- 18 before Aph and 27 +/- 12, 71 +/- 19, and 134 +/- 34
      ml.min(-1).100 mmHg(-1) after Aph (P < 0.05 for low and medium dose before vs.
      after Aph). For nonresponders, these values were 30 +/- 5, 39 +/- 6, and 78 +/- 9
      ml.min(-1).100 mmHg(-1) before Aph (P < 0.05 vs. responders), with no difference
      after Aph (P > 0.05). We found that Ado receptor blockade significantly inhibited
      exercise hyperemia only at high workloads in both responders and nonresponders (P
      < 0.05 before vs. after Aph). We conclude that there may be reduced Ado receptor
      responsiveness or sensitivity in nonresponders. Furthermore, Ado may play a
      limited role exercise hyperemia in both subgroups.

PMID- 16946028
TI  - Inhibition of mucin secretion with MARCKS-related peptide improves airway
      obstruction in a mouse model of asthma.
AB  - Allergic asthma is associated with airway epithelial cell mucous metaplasia and
      mucin hypersecretion, but the consequences of mucin hypersecretion on airway
      function are unclear. Recently, a peptide derived from the myristoylated alanine
      rich C kinase substrate protein NH(2)-terminal sequence (MANS) was shown to
      inhibit methacholine (MCh)-induced mucin secretion from airway mucous cells by
      >90%. We studied the effect of intranasal pretreatment with this peptide on
      specific airway conductance (sGaw) during challenge with MCh in mice with
      allergen-induced mucous cell metaplasia. sGaw was noninvasively measured in
      spontaneously breathing restrained mice, using a double-chamber plethysmograph.
      Pretreatment with MANS peptide, but not a control peptide [random NH(2)-terminal
      sequence (RNS)], resulted in partial inhibition of the fall in sGaw induced by 60
      mM MCh (mean +/- SE; baseline 1.15 +/- 0.06; MANS/MCh 0.82 +/- 0.05; RNS/MCh 0.55
      +/- 0.05 cmH(2)O/s). The protective effect of MANS was also seen in mice
      challenged with allergen for 3 consecutive days to increase airway
      hyperresponsiveness, although the degree of protection was less (baseline 1.1 +/-
      0.08; MANS/MCh, 0.65 +/- 0.06; RNS/MCh 0.47 +/- 0.03 cmH(2)O/s). Because routine
      sGaw measurement in mice includes nasal airways, the effectiveness of MANS was
      also confirmed in mice breathing through their mouths after nasal occlusion
      (baseline 0.92 +/- 0.05; MANS/MCh 0.83 +/- 0.06; RNS/MCh 0.61 +/- 0.03
      cmH(2)O/s). In all instances, sGaw in the MANS-pretreated group was approximately
      35% higher than in RNS-treated controls, and mucous obstruction accounted for
      approximately 50% of the MCh-induced fall in sGaw. In summary, mucin secretion
      has a significant role in airway obstruction in a mouse model of allergic asthma,
      and strategies to inhibit mucin secretion merit further investigation.

PMID- 16946030
TI  - The impact of sex and exercise duration on growth hormone secretion.
AB  - Previous research clearly indicates a linear relationship between exercise
      intensity and growth hormone (GH) release and that this relationship is
      influenced by sex. The present study examined the GH response to increasing
      exercise duration in young men and women. Fifteen healthy subjects (8 men and 7
      women) completed three randomly assigned exercise sessions (30, 60, and 120 min)
      at 70% of peak oxygen consumption. Blood samples were collected every 10 min
      beginning 30 min before exercise, for a total of 240 min. Total integrated GH
      concentration (IGHC) increased with increasing exercise duration for men and
      women (601, 1,394, and 2,360 microg/l.4 h; 659, 1,009 and 1,243 microg/l.4 h for
      30, 60, and 120 min of exercise, respectively). Regression analysis revealed that
      IGHC (logarithmically transformed) was significantly influenced by exercise
      duration (logarithmically transformed) (120 min > 60 min > 30 min) and that a
      significant sex-dependent effect was present even after adjustments for fitness
      level and percent body fat (men > women). The slope of the regression line was
      greater for men than for women (1.003 vs. 0.612; P = 0.013), but the average
      height of the regression line was greater for women (7.287 vs. 6.595; P < 0.001).
      Although GH secretory pulse half-duration was greater in women (P = 0.001), and
      GH half-life was greater in men (P = 0.001), they were not affected by exercise
      duration. The total mass of GH secreted during exercise increased with exercise
      duration (P < 0.001) but was not affected by sex (P = 0.137). Results from the
      present investigation indicate that when exercise intensity is constant, exercise
      duration significantly increases IGHC and that this relationship is sex
      dependent.

PMID- 16946031
TI  - The role of ascorbic acid and exercise in chronic ischemia of skeletal muscle in
      rats.
AB  - This study was designed to investigate the effects of peripheral arterial
      insufficiency, exercise, and vitamin C administration on muscle performance,
      cross-sectional area, and ultrastructural morphology in extensor digitorum longus
      (EDL) and soleus (Sol) muscles in rats. Adult Wistar rats were assigned to
      ischemia alone (isch), ischemia-exercised (exe), ischemia-vitamin C (vit C), and
      ischemia-exercise-vitamin C (vit C + exe) groups. Ischemia was achieved via
      unilateral ligation of the right common iliac artery. Contralateral muscles
      within the same animal served as controls. Exercise protocol consisted of 50-min
      intermittent level running performed every other day for 5 days. Vitamin C (100
      mg/kg body wt) was administered intraperitoneally on a daily basis throughout the
      14 days of the experiment. With regard to the EDL muscle, ischemia alone reduced
      muscle strength, which was not recovered after vitamin C administration. Exercise
      alone following ischemia induced the most severe structural damage and cross
      sectional area decrease in the muscle, yet the reduction in tetanic tension was
      not significant. Exercise in conjunction with vitamin C administration preserved
      ischemia-induced EDL muscle tetanic tension. In the Sol muscle, a significant
      reduction in single twitch tension after vitamin C administration was found,
      whereas the tetanic force of the ischemic Sol was not significantly decreased
      compared with the contralateral muscles in any group. Ischemic Sol muscle cross
      sectional area was reduced in all but the exe groups. In Sol, muscle strength was
      reduced in the vit C group, and mean cross-sectional area of ischemic Sol muscles
      was reduced in all groups except the exe group. These results illustrate that
      mild exercise, combined with a low dose of vitamin C supplementation, may have
      beneficial effects on ischemic EDL muscle with a smaller effect on the Sol
      muscle.

PMID- 16946032
TI  - Pharmacological inhibition of histone deacetylases by suberoylanilide hydroxamic
      acid specifically alters gene expression and reduces ischemic injury in the mouse
      brain.
AB  - Pharmacological manipulation of gene expression is considered a promising avenue
      to reduce postischemic brain damage. Histone deacetylases (HDACs) play a central
      role in epigenetic regulation of transcription, and inhibitors of HDACs are
      emerging as neuroprotective agents. In this study, we investigated the effect of
      the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) on histone acetylation
      in control and ischemic mouse brain. We report that brain histone H3 acetylation
      was constitutively present at specific lysine residues in neurons and astrocytes.
      It is noteworthy that in the ischemic brain tissue subjected to 6 h of middle
      cerebral artery occlusion, histone H3 acetylation levels drastically decreased,
      without evidence for a concomitant change of histone acetyl-transferase or
      deacetylase activities. Treatment with SAHA (50 mg/kg i.p.) increased histone H3
      acetylation within the normal brain (of approximately 8-fold after 6 h) and
      prevented histone deacetylation in the ischemic brain. These effects were
      accompanied by increased expression of the neuroprotective proteins Hsp70 and Bcl
      2 in both control and ischemic brain tissue 24 h after the insult. It is
      noteworthy that at the same time point, mice injected with SAHA at 25 and 50
      mg/kg had smaller infarct volumes compared with vehicle-receiving animals (28.5%
      and 29.8% reduction, p < 0.05 versus vehicle, Student's t test). At higher doses,
      SAHA was less efficient in increasing Bcl-2 and Hsp70 expression and did not
      afford significant ischemic neuroprotection (13.9% infarct reduction). Data
      demonstrate that pharmacological inhibition of HDACs promotes expression of
      neuroprotective proteins within the ischemic brain and underscores the
      therapeutic potential of molecules inhibiting HDACs for stroke therapy.

PMID- 16946033
TI  - Global genetic change tracks global climate warming in Drosophila subobscura.
AB  - Comparisons of recent with historical samples of chromosome inversion frequencies
      provide opportunities to determine whether genetic change is tracking climate
      change in natural populations. We determined the magnitude and direction of
      shifts over time (24 years between samples on average) in chromosome inversion
      frequencies and in ambient temperature for populations of the fly Drosophila
      subobscura on three continents. In 22 of 26 populations, climates warmed over the
      intervals, and genotypes characteristic of low latitudes (warm climates)
      increased in frequency in 21 of those 22 populations. Thus, genetic change in
      this fly is tracking climate warming and is doing so globally.

PMID- 16946034
TI  - Chemistry. A pixellated window on chemistry in solids.

PMID- 16946035
TI  - Solid ammonium sulfate aerosols as ice nuclei: a pathway for cirrus cloud
      formation.
AB  - Laboratory measurements support a cirrus cloud formation pathway involving
      heterogeneous ice nucleation by solid ammonium sulfate aerosols. Ice formation
      occurs at low ice-saturation ratios consistent with the formation of continental
      cirrus and an interhemispheric asymmetry observed for cloud onset. In a climate
      model, this mechanism provides a widespread source of ice nuclei and leads to
      fewer but larger ice crystals as compared with a homogeneous freezing scenario.
      This reduces both the cloud albedo and the longwave heating by cirrus. With the
      global ammonia budget dominated by agricultural practices, this pathway might
      further couple anthropogenic activity to the climate system.

PMID- 16946037
TI  - Irreversible organic crystalline chemistry monitored in real time.
AB  - Because multiple laser shots are typically required to monitor ultrafast
      photochemical reaction dynamics, sample depletion and product accumulation have
      greatly restricted the range of substrates and structural environments amenable
      to study. By implementing a two-dimensional spatial delay gradient across the
      profile of a femtosecond probe pulse, we can monitor in a single laser shot
      organic crystalline reaction dynamics despite the formation of permanent
      photoproducts that cannot be conveniently removed. We monitored the photolysis of
      the triiodide anion, I3-, and subsequent recombination or relaxation of its
      reaction products, in three very different pure organic molecular crystals. The
      experimental results and associated molecular dynamics simulations illustrate the
      intimate connection between lattice structure and reaction dynamics, highlighting
      the role of lattice constraints in directing phase-coherent geminate
      recombination of photofragments within a crystalline reaction cage.

PMID- 16946038
TI  - Boosting S&T innovation in Japan.

PMID- 16946036
TI  - Cancer regression in patients after transfer of genetically engineered
      lymphocytes.
AB  - Through the adoptive transfer of lymphocytes after host immunodepletion, it is
      possible to mediate objective cancer regression in human patients with metastatic
      melanoma. However, the generation of tumor-specific T cells in this mode of
      immunotherapy is often limiting. Here we report the ability to specifically
      confer tumor recognition by autologous lymphocytes from peripheral blood by using
      a retrovirus that encodes a T cell receptor. Adoptive transfer of these
      transduced cells in 15 patients resulted in durable engraftment at levels
      exceeding 10% of peripheral blood lymphocytes for at least 2 months after the
      infusion. We observed high sustained levels of circulating, engineered cells at 1
      year after infusion in two patients who both demonstrated objective regression of
      metastatic melanoma lesions. This study suggests the therapeutic potential of
      genetically engineered cells for the biologic therapy of cancer.

PMID- 16946039
TI  - Pluto. Underworld character kicked out of planetary family.

PMID- 16946040
TI  - Scholarly publishing. Particle physicists want to expand open access.

PMID- 16946041
TI  - Genetics. Genomes highlight plant pathogens' powerful arsenal.

PMID- 16946042
TI  - Emerging infectious diseases. During a hot summer, bluetongue virus invades
      northern Europe.

PMID- 16946043
TI  - Computer security. DOE tightens monitoring of lab collaborators.

PMID- 16946044
TI  - Academic careers. USC hires prepackaged team.

PMID- 16946045
TI  - Meteorology. A hurricane's punch still knocks out forecasters.

PMID- 16946046
TI  - Scientific misconduct. Truth and consequences.

PMID- 16946047
TI  - Profile: Thomas Kaplan. From making a killing to saving a species.

PMID- 16946048
TI  - Ecology. Plant wannabes.

PMID- 16946049
TI  - Plant science. Auxin begins to give up its secrets.

PMID- 16946050
TI  - Other nations catching up to United States.

PMID- 16946051
TI  - Why academic drug discovery makes sense.

PMID- 16946052
TI  - Propagation of errors in review articles.

PMID- 16946053
TI  - Role of leucine in regulating food intake.

PMID- 16946054
TI  - Comment on "A well-preserved Archaeopteryx specimen with theropod features".
AB  - On the basis of new information from the 10th specimen of Archaeopteryx, Mayr et
      al. (Reports, 2 December 2005, p. 1483) suggested that birds, or avian flight,
      originated twice. We investigate the statistical support for this phylogenetic
      hypothesis and show that it is no better supported by available morphological
      character data than the hypothesis of a single avian origin.

PMID- 16946055
TI  - Energy. A road map to U.S. decarbonization.

PMID- 16946056
TI  - Microbiology. Malaria's stealth shuttle.

PMID- 16946057
TI  - Chemistry. Controlling biological functions.

PMID- 16946058
TI  - Materials science. Step dances on silicon.

PMID- 16946059
TI  - Chemistry. Fluorous to the core.

PMID- 16946060
TI  - Geochemistry. The Hawaiian-Emperor bend: older than expected.

PMID- 16946061
TI  - Behavior. The power of social psychological interventions.

PMID- 16946062
TI  - Microarthropods mediate sperm transfer in mosses.
AB  - Among flowering plants, animals commonly act as pollinators. We showed that
      fertile moss shoots attract springtails and mites, which in turn carry moss
      sperm, thereby enhancing the fertilization process. Previously, fertilization of
      mosses was thought to depend on the capacity of individual sperm to swim through
      a continuous water layer. The role of microarthropods in moss fertilization
      resembles the role of animals as pollinators of flowering plants but may be
      evolutionarily much older because of the antiquity of the organism groups
      involved.

PMID- 16946063
TI  - Coherent control of retinal isomerization in bacteriorhodopsin.
AB  - Optical control of the primary step of photoisomerization of the retinal molecule
      in bacteriorhodopsin from the all-trans to the 13-cis state was demonstrated
      under weak field conditions (where only 1 of 300 retinal molecules absorbs a
      photon during the excitation cycle) that are relevant to understanding biological
      processes. By modulating the phases and amplitudes of the spectral components in
      the photoexcitation pulse, we showed that the absolute quantity of 13-cis retinal
      formed upon excitation can be enhanced or suppressed by +/-20% of the yield
      observed using a short transform-limited pulse having the same actinic energy.
      The shaped pulses were shown to be phase-sensitive at intensities too low to
      access different higher electronic states, and so these pulses apparently steer
      the isomerization through constructive and destructive interference effects, a
      mechanism supported by observed signatures of vibrational coherence. These
      results show that the wave properties of matter can be observed and even
      manipulated in a system as large and complex as a protein.

PMID- 16946065
TI  - Anomalous spiral motion of steps near dislocations on silicon surfaces.
AB  - We have used low-energy electron microscopy to measure step motion on Si(111) and
      Si(001) near dislocations during growth and sublimation. Steps on Si(111) exhibit
      the classic rotating Archimedean spiral motion, as predicted by Burton, Cabrera,
      and Frank. Steps on Si(001), however, move in a strikingly different manner. The
      strain-relieving anomalous behavior can be understood in detail by considering
      how the local step velocity is affected by the nonuniform strain field arising
      from the dislocation. We show how the dynamic step-flow pattern is related to the
      dislocation slip system.

PMID- 16946064
TI  - Phytophthora genome sequences uncover evolutionary origins and mechanisms of
      pathogenesis.
AB  - Draft genome sequences have been determined for the soybean pathogen Phytophthora
      sojae and the sudden oak death pathogen Phytophthora ramorum. Oomycetes such as
      these Phytophthora species share the kingdom Stramenopila with photosynthetic
      algae such as diatoms, and the presence of many Phytophthora genes of probable
      phototroph origin supports a photosynthetic ancestry for the stramenopiles.
      Comparison of the two species' genomes reveals a rapid expansion and
      diversification of many protein families associated with plant infection such as
      hydrolases, ABC transporters, protein toxins, proteinase inhibitors, and, in
      particular, a superfamily of 700 proteins with similarity to known oomycete
      avirulence genes.

PMID- 16946066
TI  - Chemically induced fast solid-state transitions of omega-VOPO4 in vanadium
      phosphate catalysts.
AB  - Vanadium phosphates are important catalysts for the oxidation of alkanes, and
      commercial catalysts comprise a complex range of V4+ and V5+ phosphates. We used
      three complementary in situ characterization methodologies-powder x-ray
      diffraction and laser Raman and electron paramagnetic resonance spectroscopies-to
      show that the metastable phase omega-VOPO4 is very sensitive to many of the
      reactants and products of butane oxidation. A rapid transformation from omega
      VOPO4 to delta-VOPO4 occurs on exposure to butane at the reaction temperature,
      and hence the metastable omega-VOPO4 may play a role in the formation of
      commercial catalysts.

PMID- 16946067
TI  - Fluorous nanodroplets structurally confined in an organopalladium sphere.
AB  - The distinct properties of fluorous phases are practically useful for separation,
      purification, and reaction control in organic synthesis. Here, we report the
      formation of a liquid-like fluorous droplet, composed of 24 perfluoroalkyl chains
      confined in the interior of a 5-nanometer-sized, roughly spherical shell that
      spontaneously assembled in solution from 12 palladium ions and 24 bridging
      ligands. Crystallographic analysis confirmed the rigid shell framework and
      amorphous interior. Perfluoroalkanes can dissolve in this well-defined fluorous
      phase, whereas they can hardly dissolve in a surrounding polar organic solution,
      and their solubility (up to approximately eight perfluoroalkane molecules per
      spherical complex) can be finely controlled by tuning the length of
      perfluoroalkyl chains tethered to the shell.

PMID- 16946068
TI  - Triple-bond reactivity of diphosphorus molecules.
AB  - We report a mild method for generating the diphosphorus molecule or its synthetic
      equivalent in homogeneous solution; the P2 allotrope of the element phosphorus is
      normally obtained only under extreme conditions (for example, from P4 at 1100
      kelvin). Diphosphorus is extruded from a niobium complex designed for this
      purpose and can be trapped efficiently by two equivalents of an organic diene to
      produce an organodiphosphorus compound. Diphosphorus stabilized by coordination
      to tungsten pentacarbonyl can be generated similarly at 25 degrees C, and in this
      stabilized form it still efficiently consumes two organic diene molecules for
      every diphosphorus unit.

PMID- 16946069
TI  - 50-Ma initiation of Hawaiian-Emperor bend records major change in Pacific plate
      motion.
AB  - The Hawaiian-Emperor bend has played a prominent yet controversial role in
      deciphering past Pacific plate motions and the tempo of plate motion change. New
      ages for volcanoes of the central and southern Emperor chain define large changes
      in volcanic migration rate with little associated change in the chain's trend,
      which suggests that the bend did not form by slowing of the Hawaiian hot spot.
      Initiation of the bend near Kimmei seamount about 50 million years ago (MA) was
      coincident with realignment of Pacific spreading centers and early magmatism in
      western Pacific arcs, consistent with formation of the bend by changed Pacific
      plate motion.

PMID- 16946070
TI  - Corridors increase plant species richness at large scales.
AB  - Habitat fragmentation is one of the largest threats to biodiversity. Landscape
      corridors, which are hypothesized to reduce the negative consequences of
      fragmentation, have become common features of ecological management plans
      worldwide. Despite their popularity, there is little evidence documenting the
      effectiveness of corridors in preserving biodiversity at large scales. Using a
      large-scale replicated experiment, we showed that habitat patches connected by
      corridors retain more native plant species than do isolated patches, that this
      difference increases over time, and that corridors do not promote invasion by
      exotic species. Our results support the use of corridors in biodiversity
      conservation.

PMID- 16946071
TI  - Exploiting the reversibility of natural product glycosyltransferase-catalyzed
      reactions.
AB  - Glycosyltransferases (GTs), an essential class of ubiquitous enzymes, are
      generally perceived as unidirectional catalysts. In contrast, we report that four
      glycosyltransferases from two distinct natural product biosynthetic pathways
      calicheamicin and vancomycin-readily catalyze reversible reactions, allowing
      sugars and aglycons to be exchanged with ease. As proof of the broader
      applicability of these new reactions, more than 70 differentially glycosylated
      calicheamicin and vancomycin variants are reported. This study suggests the
      reversibility of GT-catalyzed reactions may be general and useful for generating
      exotic nucleotide sugars, establishing in vitro GT activity in complex systems,
      and enhancing natural product diversity.

PMID- 16946072
TI  - Structural asymmetry of AcrB trimer suggests a peristaltic pump mechanism.
AB  - The AcrA/AcrB/TolC complex spans the inner and outer membranes of Escherichia
      coli and serves as its major drug-resistance pump. Driven by the proton motive
      force, it mediates the efflux of bile salts, detergents, organic solvents, and
      many structurally unrelated antibiotics. Here, we report a crystallographic
      structure of trimeric AcrB determined at 2.9 and 3.0 angstrom resolution in space
      groups that allow asymmetry of the monomers. This structure reveals three
      different monomer conformations representing consecutive states in a transport
      cycle. The structural data imply an alternating access mechanism and a novel
      peristaltic mode of drug transport by this type of transporter.

PMID- 16946073
TI  - Human lineage-specific amplification, selection, and neuronal expression of
      DUF1220 domains.
AB  - Extreme gene duplication is a major source of evolutionary novelty. A genome-wide
      survey of gene copy number variation among human and great ape lineages revealed
      that the most striking human lineage-specific amplification was due to an unknown
      gene, MGC8902, which is predicted to encode multiple copies of a protein domain
      of unknown function (DUF1220). Sequences encoding these domains are virtually all
      primate-specific, show signs of positive selection, and are increasingly
      amplified generally as a function of a species' evolutionary proximity to humans,
      where the greatest number of copies (212) is found. DUF1220 domains are highly
      expressed in brain regions associated with higher cognitive function, and in
      brain show neuron-specific expression preferentially in cell bodies and
      dendrites.

PMID- 16946074
TI  - Reducing the racial achievement gap: a social-psychological intervention.
AB  - Two randomized field experiments tested a social-psychological intervention
      designed to improve minority student performance and increase our understanding
      of how psychological threat mediates performance in chronically evaluative real
      world environments. We expected that the risk of confirming a negative stereotype
      aimed at one's group could undermine academic performance in minority students by
      elevating their level of psychological threat. We tested whether such
      psychological threat could be lessened by having students reaffirm their sense of
      personal adequacy or "self-integrity." The intervention, a brief in-class writing
      assignment, significantly improved the grades of African American students and
      reduced the racial achievement gap by 40%. These results suggest that the racial
      achievement gap, a major social concern in the United States, could be
      ameliorated by the use of timely and targeted social-psychological interventions.

PMID- 16946075
TI  - A role for the macaque anterior cingulate gyrus in social valuation.
AB  - Complex human social interaction is disrupted when the frontal lobe is damaged in
      disease, and in extreme cases patients are described as having acquired
      sociopathy. We compared, in macaques, the effects of lesions in subdivisions of
      the anterior cingulate and the orbitofrontal cortices believed to be anatomically
      homologous to those damaged in such patients. We show that the anterior cingulate
      gyrus in male macaques is critical for normal patterns of social interest in
      other individual male or female macaques. Conversely, the orbitofrontal cortex
      lesion had a marked effect only on responses to mildly fear-inducing stimuli.
      These results suggest that damage to the anterior cingulate gyrus may be the
      cause of changes in social interaction seen after frontal lobe damage.

PMID- 16946076
TI  - Urethane inhibits the GABAergic neurotransmission in the nucleus of the solitary
      tract of rat brain stem slices.
AB  - Because urethane is a widely used anesthetic in animal experimentation, in the
      present study, we evaluated its effects on neurons of the nucleus of the solitary
      tract (NTS) in brain stem slices from young rats (25-30 days old). Using the
      whole cell configuration of the patch-clamp technique, spontaneous postsynaptic
      currents (sPSCs) and evoked excitatory postsynaptic currents (eEPSCs) were
      recorded. Urethane (20 mM) decreased by approximately 60% the frequency of
      GABAergic sPSCs (1.0 +/- 0.2 vs. 0.4 +/- 0.1 Hz) but did not change the
      frequency, amplitude, or half-width of glutamatergic events or TTX-resistant
      inhibitory sPSCs [miniature inhibitory postsynaptic currents (IPSCs)]. Miniature
      IPSCs were measured in the presence of urethane plus 1 mM diazepam (1 mM), and no
      changes were seen in their amplitude. This suggests that the GABA concentration
      in the NTS synapses is set at saturating level. We also evaluated the effect of
      urethane on eEPSCs, and no significant change was observed in the amplitude of N
      methyl-d-aspartate [NMDA; 44.2 +/- 11.5 vs. 37.6 +/- 10.6 pA (holding potential =
      40 mV)] and non-NMDA currents [204.4 +/- 35.5 vs. 196.6 +/- 31.2 pA (holding
      potential = -70 mV)]. Current-clamp experiments showed that urethane did not
      alter the action potential characteristics and passive membrane properties. These
      data suggest that urethane has an inhibitory effect on GABAergic neurons in the
      NTS but does not change the spontaneous or evoked excitatory responses.

PMID- 16946077
TI  - Ghrelin and sleep-wake regulation.

PMID- 16946078
TI  - Burn-induced increase in atrogin-1 and MuRF-1 in skeletal muscle is
      glucocorticoid independent but downregulated by IGF-I.
AB  - The present study determined whether thermal injury increases the expression of
      the ubiquitin (Ub) E3 ligases referred to as muscle ring finger (MuRF)-1 and
      muscle atrophy F-box (MAFbx; aka atrogin-1), which are muscle specific and
      responsible for the increased protein breakdown observed in other catabolic
      conditions. After 48 h of burn injury (40% total body surface area full-thickness
      scald burn) gastrocnemius weight was reduced, and this change was associated with
      an increased mRNA abundance for atrogin-1 and MuRF-1 (3.1- to 8-fold,
      respectively). Similarly, burn increased polyUb mRNA content in the gastrocnemius
      twofold. In contrast, there was no burn-induced atrophy of the soleus and no
      significant change in atrogin-1, MuRF-1, or polyUb mRNA. Burns also did not alter
      E3 ligase expression in heart. Four hours after administration of the anabolic
      agent insulin-like growth factor (IGF)-I to burned rats, the mRNA content of
      atrogin-1 and polyUb in gastrocnemius had returned to control values and the
      elevation in MuRF-1 was reduced 50%. In contrast, leucine did not alter E3 ligase
      expression. In a separate study, in vivo administration of the proteasome
      inhibitor Velcade prevented burn-induced loss of muscle mass determined at 48 h.
      Finally, administration of the glucocorticoid receptor antagonist RU-486 did not
      prevent burn-induced atrophy of the gastrocnemius or the associated elevation in
      atrogin-1, MuRF-1, or polyUb. In summary, the acute muscle wasting accompanying
      thermal injury is associated with a glucocorticoid-independent increase in the
      expression of several Ub E3 ligases that can be downregulated by IGF-I.

PMID- 16946079
TI  - IL-1beta and LPS induce anorexia by distinct mechanisms differentially dependent
      on microsomal prostaglandin E synthase-1.
AB  - Recent work demonstrated that the febrile response to peripheral immune
      stimulation with proinflammatory cytokine IL-1beta or bacterial wall
      lipopolysaccharide (LPS) is mediated by induced synthesis of prostaglandin E(2)
      by the terminal enzyme microsomal prostaglandin E synthase-1 (mPGES-1). The
      present study examined whether a similar mechanism might also mediate the
      anorexia induced by these inflammatory agents. Transgenic mice with a deletion of
      the Ptges gene, which encodes mPGES-1, and wild-type controls were injected
      intraperitoneally with IL-1beta, LPS, or saline. Mice were free fed, and food
      intake was continuously monitored with an automated system for 12 h. Body weight
      was recorded every 24 h for 4 days. The IL-1beta induced anorexia in wild-type
      but not knock-out mice, and so it was almost completely dependent on mPGES-1. In
      contrast, LPS induced anorexia of the same magnitude in both phenotypes, and
      hence it was independent of mPGES-1. However, when the mice were prestarved for
      22 h, LPS induced anorexia and concomitant body weight loss in the knock-out
      animals that was attenuated compared with the wild-type controls. These data
      suggest that IL-1beta and LPS induce anorexia by distinct immune-to-brain
      signaling pathways and that the anorexia induced by LPS is mediated by a
      mechanism different from the fever induced by LPS. However, nutritional state
      and/or motivational factors also seem to influence the pathways for immune
      signaling to the brain. Furthermore, both IL-1beta and LPS caused reduced meal
      size but not meal frequency, suggesting that both agents exerted an anhedonic
      effect during these experimental conditions.

PMID- 16946081
TI  - Maternal dexamethasone treatment at midgestation reduces nephron number and
      alters renal gene expression in the fetal spiny mouse.
AB  - We investigated the effects of maternal glucocorticoid exposure in the spiny
      mouse, a precocial species with a relatively long gestation, few offspring, and
      in which nephrogenesis is complete before birth. We hypothesized that exposure of
      the fetus to glucocorticoids before the formation of glomeruli would result in
      adult hypertensive offspring with fewer nephrons. Furthermore, we hypothesized
      that this nephron deficit would result from changes in expression of genes
      involved in branching morphogenesis. Osmotic pumps implanted in pregnant spiny
      mice at midgestation (day 20) delivered dexamethasone (dex; 125 microg/kg) or
      saline for 60 h. Females were killed at day 23 of gestation and kidneys were
      frozen for real-time PCR analysis or allowed to deliver their offspring. At 20 wk
      of age, blood pressure was measured in the offspring for 1 wk before nephron
      number was determined using unbiased stereology. Males and females exposed to dex
      had significantly fewer nephrons (male: saline: 7,870 +/- 27, dex: 6,878 +/- 173;
      female: saline: 7,526 +/- 62, dex: 5,886 +/- 382; P < 0.001) compared with
      controls. Dex had no effect on basal blood pressure. Fetal kidneys collected at
      day 23 of gestation from dex-exposed mothers showed increased mRNA expression of
      BMP4 (P < 0.05), TGF-beta(1) (P < 0.05), genes known to inhibit branching
      morphogenesis and gremlin (P < 0.01), an antagonist of BMP4, compared with saline
      controls. This study shows for the first time an upregulation of branching
      morphogenic genes in the fetal kidney in a model of excess maternal
      glucocorticoids that leads to a nephron deficit in the adult. This study also
      provides evidence that a reduced nephron number does not necessarily lead to
      development of hypertension.

PMID- 16946080
TI  - Quantitative trait loci for carbohydrate and total energy intake on mouse
      chromosome 17: congenic strain confirmation and candidate gene analyses (Glo1,
      Glp1r).
AB  - Quantitative trait loci (QTL) for carbohydrate (Mnic1) and total energy (Kcal2)
      intake on proximal mouse chromosome 17 were identified previously from a C57BL/6J
      (B6) X CAST/Ei (CAST) intercross. Here we report that a new congenic strain
      developed in our laboratory has confirmed this complex locus by recapitulating
      the original linked phenotypes: B6.CAST-17 homozygous congenic mice consumed more
      carbohydrate (27%) and total energy (17%) compared with littermate wild-type
      mice. Positional gene candidates with relevance to carbohydrate metabolism,
      glyoxalase I (Glo1) and glucagon-like peptide-1 receptor (Glp1r), were evaluated.
      Glo1 expression was upregulated in liver and hypothalamus of congenic mice when
      compared with B6 mice. Analyses of Glp1r mRNA and protein expression revealed
      tissue-specific strain differences in pancreas (congenic>B6) and stomach
      (B6>congenic). These results suggest the possibility of separate mechanisms for
      enhanced insulin synthesis and gastric accommodation in the presence of high
      carbohydrate intake and larger food volume, respectively. Sequence analysis of
      Glp1r found a G insert at nt position 1349, which results in earlier termination
      of the open reading frame, thus revealing an error in the public sequence.
      Consequently, the predicted length of GLP-1R is 463 aa compared with 489 aa, as
      previously reported. Also, we found a polymorphism in Glp1r between parental
      strains that alters the amino acid sequence. Variation in Glp1r could influence
      nutrient intake in this model through changes in the regulatory or protein coding
      regions of the gene. These congenic mice offer a powerful tool for investigating
      gene interactions in the control of food intake.

PMID- 16946082
TI  - Cross-organ interactions between reproductive, gastrointestinal, and urinary
      tracts: modulation by estrous stage and involvement of the hypogastric nerve.
AB  - Central nervous system neurons process information converging from the uterus,
      colon, and bladder, partly via the hypogastric nerve. This processing is
      influenced by the estrous cycle, suggesting the existence of an estrous
      modifiable central nervous system substrate by which input from one pelvic organ
      can influence functioning of other pelvic organs. Here, we tested predictions
      from this hypothesis that acute inflammation of colon, uterine horn, or bladder
      would produce signs of inflammation in the other uninflamed organs (increase
      vascular permeability) and that cross-organ effects would vary with estrous and
      be eliminated by hypogastric neurectomy (HYPX). Under urethane anesthesia, the
      colon, uterine horn, or bladder of rats in proestrus or metestrus, with or
      without prior HYPX, was treated with mustard oil or saline. Two hours later,
      Evans Blue dye extravasation was measured to assess vascular permeability.
      Extravasation was increased in all inflamed organs, regardless of estrous stage.
      For rats in proestrus, but not metestrus, either colon or uterine horn
      inflammation significantly increased extravasation in the uninflamed bladder.
      Much smaller cross-organ effects were seen in colon and uterine horn. HYPX
      reduced extravasation in the inflamed colon and inflamed uterine horn, but not
      the inflamed bladder. HYPX eliminated the colon-to-bladder and uterine horn-to
      bladder effects. These results demonstrate that inflaming one pelvic organ can
      produce estrous-modifiable signs of inflammation in other pelvic organs,
      particularly bladder, and suggest that the cross-organ effects involve the
      hypogastric nerve and are at least partly centrally mediated. Such effects could
      contribute to co-occurrence and cyclicity of distressing pelvic disorders in
      women.

PMID- 16946083
TI  - Effect of aging on the cardiovascular regulatory systems in healthy women.
AB  - Aging, independently from the hormonal status, is a major risk factor for
      cardiovascular morbidity in healthy women. Therefore, we studied the effect of
      healthy aging on the cardiovascular homeostatic mechanisms in premenopausal and
      postmenopausal women with similar estrogen levels. Twelve healthy postmenopausal
      women, confirmed by follicular-stimulating hormone (FSH) and luteal hormone (LH)
      levels, were compared with 14 normally menstruating women during the early
      follicular phase (young-EF), to avoid as much as possible the effects of
      estrogen. Systolic BP was 108 +/- 1.5 vs. 123 +/- 2.5 (P < 0.001), supine
      norepinephrine was 260 +/- 30 vs. 216 +/- 45 and upright 640 +/- 100 vs. 395 +/-
      50 pg/ml (P = 0.05) in young-EF vs. postmenopausal, respectively. Plasma renin
      activity and aldosterone remained unchanged. Vagal cardiac tone indices decreased
      significantly with aging (young-EF vs. postmenopausal): high-frequency (HF) band,
      root mean square successive differences (rMSSD) and proportion of R-R intervals
      >50 ms (PNN50%) were 620 +/- 140 vs. 270 +/- 70 (P = 0.04), 53 +/- 7 vs. 30 +/- 3
      (P = 0.02), and 23 +/- 5 vs. 10 +/- 3 (P = 0.04), respectively. LF to HF ratio
      was 0.85 +/- 0.17 in young-EF and became 1.5 +/- 0.22 in postmenopausal (P =
      0.03). Both arms of the baroreflex, +BRS (29 +/- 5 vs. 13.5 +/- 2.5, P = 0.01)
      and -BRS (26 +/- 4 vs. 15 +/- 1.5, P = 0.02) decreased with aging. Cardiovascular
      alpha(1)-adrenoreceptor responsiveness significantly increased and beta-decreased
      in postmenopausal compared with young EF (P < 0.001, both). The corrected QT
      intervals (QTc) were similar, whereas corrected JT intervals (JTc) and JTc to QTc
      ratio were prolonged in the postmenopausal group. We conclude that in young
      women, parasympathetic control is the main regulator of the cardiovascular system
      and in postmenopausal women, sympathetic tone dominates. The transition from
      parasympathetic to sympathetic control may contribute to the increased
      cardiovascular morbidity with aging.

PMID- 16946084
TI  - Social defeat and footshock increase body mass and adiposity in male Syrian
      hamsters.
AB  - Obesity is a world-wide epidemic, and many factors, including stress, have been
      linked to this growing trend. After social stress (i.e., defeat), subordinate
      laboratory rats and most laboratory mice become hypophagic and, subsequently,
      lose body mass; the opposite is true of subordinate Syrian hamsters. After social
      defeat, Syrian hamsters become hyperphagic and gain body mass compared with
      nonstressed controls. It is unknown whether this increase in body mass and food
      intake is limited to subordinate hamsters. In experiment 1, we asked, do dominant
      hamsters increase food intake, body mass, and adiposity after an agonistic
      encounter? Subordinate hamsters increased food intake and body mass compared with
      nonstressed controls. Although there was no difference in food intake or absolute
      body mass between dominant and nonstressed control animals, cumulative body mass
      gain was significantly higher in dominant than in nonstressed control animals.
      Total carcass lipid and white adipose tissue (WAT) (i.e., retroperitoneal and
      epididymal WAT) masses were significantly increased in subordinate, but not
      dominant, hamsters compared with nonstressed controls. In experiment 2, we asked,
      does footshock stress increase food intake, body mass, and adiposity. Hamsters
      exposed to defeat, but not footshock stress, increased food intake relative to
      nonstressed controls. In animals exposed to defeat or footshock stress, body
      mass, as well as mesenteric WAT mass, increased compared with nonstressed
      controls. Collectively, these data demonstrate that social and nonsocial
      stressors increase body and lipid mass in male hamsters, suggesting that this
      species may prove useful for studying the physiology of stress-induced obesity in
      some humans.

PMID- 16946085
TI  - Differential expression of neuronal ACE2 in transgenic mice with overexpression
      of the brain renin-angiotensin system.
AB  - Angiotensin-converting enzyme 2 (ACE2) is a newly discovered carboxy-peptidase
      responsible for the formation of vasodilatory peptides such as angiotensin-(1-7).
      We hypothesized that ACE2 is part of the brain renin-angiotensin system, and its
      expression is regulated by the other elements of this system. ACE2 immunostaining
      was performed in transgenic mouse brain sections from neuron-specific enolase
      AT(1A) (overexpressing AT(1A) receptors), R(+)A(+) (overexpressing
      angiotensinogen and renin), and control (nontransgenic littermates) mice. Results
      show that ACE2 staining is widely distributed throughout the brain. Using cell
      type-specific antibodies, we observed that ACE2 staining is present in the
      cytoplasm of neuronal cell bodies but not in glial cells. In the subfornical
      organ, an area lacking the blood-brain barrier and sensitive to blood-borne
      angiotensin II, ACE2 was significantly increased in transgenic mice.
      Interestingly, ACE2 mRNA and protein expression were inversely correlated in the
      nucleus of tractus solitarius/dorsal motor nucleus of the vagus and the
      ventrolateral medulla, when comparing transgenic to nontransgenic mice. These
      results suggest that ACE2 is localized to the cytoplasm of neuronal cells in the
      brain and that ACE2 levels appear highly regulated by other components of the
      renin-angiotensin system, confirming its involvement in this system. Moreover,
      ACE2 expression in brain structures involved in the control of cardiovascular
      function suggests that the carboxypeptidase may have a role in the central
      regulation of blood pressure and diseases involving the autonomic nervous system,
      such as hypertension.

PMID- 16946086
TI  - Sex-dependent differences in the regulation of myocardial protein synthesis
      following long-term ethanol consumption.
AB  - Chronic heavy alcohol consumption alters cardiac structure and function.
      Controversies remain as to whether hearts from females respond to the chronic
      ethanol intake in a manner analogous to males. In particular, sex differences in
      the myocardial response to chronic alcohol consumption remain unresolved at the
      molecular level. The purpose of the present set of experiments was to determine
      whether alterations in cardiac structure and protein metabolism show sexual
      dimorphism following chronic alcohol consumption for 26 wk. In control animals,
      hearts from female rats showed lowered heart weights and had thinner ventricular
      walls compared with males. The smaller heart size was associated with a lower
      protein content that occurred in part from a reduced rate of protein synthesis.
      Chronic alcohol consumption in males, but not in females, caused a thinning of
      the ventricular wall and intraventricular septum, as assessed by
      echocardiography, correlating with the loss of heart mass. The alterations in
      cardiac size occurred, in part, through a lowering of the protein content
      secondary to a diminished rate of protein synthesis. The decreased rate of
      protein synthesis appeared related to a reduced assembly of active eukaryotic
      initiation factor (eIF)4G.eIF4E complex secondary to both a diminished
      phosphorylation of eIF4G and increased formation of inactive 4Ebinding protein
      (4EBP1).eIF4E complex. The latter effects occurred as a result of decreased
      phosphorylation of 4EBP1. None of these ethanol-induced alterations in hearts
      from males were observed in hearts from females. These data suggest that chronic
      alcohol-induced impairments in myocardial protein synthesis results, in part,
      from marked decreases in eIF4E.eIF4G complex formation in males. The failure of
      female rats consuming ethanol to show structural changes appears related to the
      inability of ethanol to affect the regulation protein synthesis to the same
      extent as their male counterparts.

PMID- 16946087
TI  - Visualization in zebrafish larvae of Na(+) uptake in mitochondria-rich cells
      whose differentiation is dependent on foxi3a.
AB  - Uptake of Na(+) from the environment is an indispensable strategy for the
      survival of freshwater fish, as they easily lose Na(+) from the plasma to a
      diluted environment. Nevertheless, the location of and molecules involved in
      Na(+) uptake remain poorly understood. In this study, we utilized Sodium Green, a
      Na(+)-dependent fluorescent reagent, to provide direct evidence that Na(+)
      absorption takes place in a subset of the mitochondria-rich (MR) cells on the
      yolk sac surface of zebrafish larvae. Combined with immunohistochemistry, we
      revealed that the Na(+)-absorbing MR cells were exceptionally rich in vacuolar
      type H(+)-ATPase (H(+)-ATPase) but moderately rich in Na(+)-K(+)-ATPase. We also
      addressed the function of foxi3a, a transcription factor that is specifically
      expressed in the H(+)-ATPase-rich MR cells. When foxi3a was depleted from
      zebrafish embryos by antisense morpholino oligonucleotide injection,
      differentiation of the MR cells was completely blocked and Na(+) influx was
      severely reduced, indicating that MR cells are the primary sites for Na(+)
      absorption. Additionally, foxi3a expression is initiated at the gastrula stage in
      the presumptive ectoderm; thus, we propose that foxi3a is a key gene in the
      control of MR cell differentiation. We also utilized a set of ion transport
      inhibitors to assess the molecules involved in the process and discuss the
      observations.

PMID- 16946088
TI  - On pulmonary rehabilitation and the flight of the bumblebee: the ATS/ERS
      Statement on Pulmonary Rehabilitation.

PMID- 16946089
TI  - Idiopathic pulmonary fibrosis: treatment options in pursuit of evidence-based
      approaches.

PMID- 16946090
TI  - How should we treat portopulmonary hypertension?

PMID- 16946091
TI  - Ventilatory assistance in patients with Duchenne muscular dystrophy.

PMID- 16946092
TI  - HERMES: good reasons for harmonising education and training in respiratory
      medicine.

PMID- 16946094
TI  - Corticosteroid treatment in sarcoidosis.
AB  - At present there is no curative treatment for sarcoidosis. Immunosuppressive
      and/or immunomodulatory drugs can, however, be used for controlling the disease.
      Corticosteroids remain the mainstay of therapy. They function by suppressing the
      pro-inflammatory cytokines and chemokines that are involved in cell-mediated
      immune responses and granuloma formation. Only in a select group of patients is
      it justifiable to use these drugs, after careful evaluation of the pros and cons.
      Importantly, disease severity, e.g. threatened organ functions, and not disease
      activity itself should be the deciding factor in this process. In the case of
      parenchymal involvement, there is substantial evidence that corticosteroids can
      improve respiratory symptoms and chest radiography and lung function parameters
      over 6-24 months. Other generally acknowledged (empirical) criteria for systemic
      treatment include neurological, cardiac and sight-threatening ocular involvement
      and hypercalcaemia. Remarkably, despite >50 yrs of use, there is no proof of long
      term (survival) benefit from corticosteroid treatment. In addition, there are
      still no data regarding the optimal dose and duration of corticosteroid or other
      immunosuppressive therapy. One of the weightiest questions remaining is whether
      or not these drugs can prevent scarring in patients with a fibrogenic phenotype.
      As new agents, including infliximab and thalidomide, enter the stage and new
      diagnostic tools are now available, there is clearly a momentum to design
      multicentric randomised controlled trials with long enough follow-up (>5 yrs) to
      answer this pivotal question.

PMID- 16946093
TI  - Toll-like receptor mRNA levels in alveolar macrophages after inhalation of
      endotoxin.
AB  - Toll-like receptors (TLRs) are pattern-recognition receptors that have been
      implicated in the initiation of innate immune responses upon the first encounter
      with invading pathogens. The airways are frequently exposed to various types of
      lipopolysaccharide (LPS) from the environment or from pathogens. The current
      study was designed to determine the effect of LPS on TLR gene expression in human
      alveolar macrophages in vivo. In total, 16 healthy subjects were enrolled in a
      single-blinded, placebo-controlled study. Subjects inhaled 100 microg LPS or
      normal saline (n = 8 per group). Measurements were performed in alveolar
      macrophages purified from bronchoalveolar lavage fluid obtained 6 h post
      challenge. Inhalation of LPS by healthy human volunteers resulted in enhanced
      alveolar macrophage expression of mRNAs encoding TLRs 1, 2, 7, 8 and CD14, and
      reduced expression of mRNAs encoding TLR4 and lymphocyte antigen 96. In
      conclusion, lipopolysaccharide differentially influences the toll-like receptor
      mRNA expression profile in human alveolar macrophages in vivo.

PMID- 16946095
TI  - Management of spontaneous pneumothorax: state of the art.
AB  - Spontaneous pneumothorax remains a significant health problem. However, with
      time, there have been improvements in pathogenesis, diagnostic procedures and
      both medical and surgical approaches to treatment. Owing to better imaging
      techniques, it is now clear that there is almost no normal visceral pleura in the
      case of spontaneous pneumothorax, and that blebs and bullae are not always the
      cause of pneumothorax. In first episodes of primary spontaneous pneumothorax,
      observation and simple aspiration are established first-line therapies, as proven
      by randomised controlled trials. Aspiration should be better promoted in daily
      medical practice. In the case of recurrent or persistent pneumothorax, simple
      talc poudrage under thoracoscopy has been shown to be safe, cost-effective and no
      more painful than a conservative treatment using a chest tube. There are also new
      experimental data showing that talc poudrage, as used in Europe, does not lead to
      serious side-effects and is currently the best available pleural sclerosing
      agent. Alternatively, surgical techniques have considerably improved, and are now
      less invasive, especially due to the development of video-assisted thoracoscopic
      surgery. Studies suggest that video-assisted thoracoscopic surgery may be more
      cost-effective than chest tube drainage in spontaneous pneumothorax requiring
      chest tube drainage, although it is more expensive than simple thoracoscopy and
      requires general anaesthesia, double-lumen tube intubation and ventilation.
      Recommendations are made regarding the treatment of pneumothorax. In secondary or
      complicated primary pneumothorax, i.e. recurrent or persistent pneumothorax, some
      diffuse treatment of the visceral pleura should be offered, either by talc
      poudrage under thoracoscopy or by video-assisted thoracoscopic surgery. Moreover,
      all of these new techniques should be better standardised to permit comparison in
      randomised controlled studies.

PMID- 16946096
TI  - c-Jun N-terminal kinase-dependent mechanisms in respiratory disease.
AB  - Respiratory diseases pose a multifaceted dilemma. Although the symptoms and
      pathology are obvious and provide multiple opportunities for therapeutic
      investigation, at the same time, the molecular complexities and prioritisation
      are overwhelming. Even within a disease such as asthma, the number of inducers,
      cell types, secondary mediators, chemical changes, immune responses and tissue
      modifications is remarkable. One means of therapeutically targeting this
      complexity is to identify individual factors responsible for regulating multiple
      disease processes. The mitogen-activated protein kinase family integrates
      multiple diverse stimuli, and, in turn, initiates a cell response by
      phosphorylating and thereby modulating the activity of many target proteins. The
      c-Jun N-terminal kinase is a critical regulator of pro-inflammatory genes, tissue
      remodelling and apoptosis, and, therefore, represents an attractive target for
      novel therapies. Pre-clinical and clinical investigation into the efficacy of c
      Jun N-terminal kinase inhibitors has been ongoing since the late 1990s. Over the
      course of this work, hypotheses have shifted as to the role of c-Jun N-terminal
      kinase in the many processes that promote allergic, inflammatory, obstructive and
      fibrotic diseases of the lung. Inhibition of c-Jun N-terminal kinase may indeed
      provide a means of suppressing more pathological mechanisms in respiratory
      disease than first suspected.

PMID- 16946097
TI  - An unusual case of mediastinal mass due to Fonsecaea pedrosoi.
AB  - Phaeohyphomycosis is a disease caused by dematiaceous fungi. Here, the first
      culture-proven case of mediastinal mass due to Fonsecaea pedrosoi is reported.
      The patient was a 40-yr-old male who had presented with history of dyspnoea and
      dysphagia. Computed tomography of the chest disclosed a mediastinal mass.
      Cultures of a specimen from the mediastinum grew Fonsecaea pedrosoi. The patient
      received amphotericin B and itraconazole and showed a remarkable recovery. Repeat
      computed tomography revealed a reduction in the mediastinal mass. The case
      highlights the need for a high degree of clinical suspicion and appropriate
      histopathological and mycological examination of clinical specimens.

PMID- 16946098
TI  - A 46-year-old female with dyspnoea, stridor and chronic cough.

PMID- 16946099
TI  - Angiotensin II blockers in obstructive pulmonary disease: a randomised controlled
      trial.

PMID- 16946100
TI  - Delirium induced by clarithromycin in a patient with community-acquired
      pneumonia.

PMID- 16946102
TI  - Studies to investigate the in vivo therapeutic window of the gamma-secretase
      inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6
      oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide (LY411,575) in the
      CRND8 mouse.
AB  - Accumulation of amyloid beta-peptide (Abeta) is considered a key step in the
      etiology of Alzheimer's disease. Abeta is produced by sequential cleavage of the
      amyloid precursor protein by beta- and gamma-secretase enzymes. Consequently,
      inhibition of gamma-secretase provides a promising therapeutic approach to treat
      Alzheimer's disease. Preclinically, several gamma-secretase inhibitors have been
      shown to reduce plasma and brain Abeta, although they also produce mechanism
      based side effects, including thymus atrophy and intestinal goblet cell
      hyperplasia. The present studies sought to establish an efficient screen for
      determining the therapeutic window of gamma-secretase inhibitors and to test
      various means of maximizing this window. Six-day oral administration of the gamma
      secretase inhibitor N(2)-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N(1)
      [(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-l-alaninamide
      (LY411,575) reduced cortical Abeta(40) in young (preplaque) transgenic CRND8 mice
      (ED(50) approximately 0.6 mg/kg) and produced significant thymus atrophy and
      intestinal goblet cell hyperplasia at higher doses (>3 mg/kg). The therapeutic
      window was similar after oral and subcutaneous administration and in young and
      aged CRND8 mice. Both the thymus and intestinal side effects were reversible
      after a 2-week washout period. Three-week treatment with 1 mg/kg LY411,575
      reduced cortical Abeta(40) by 69% without inducing intestinal effects, although a
      previously unreported change in coat color was observed. These studies
      demonstrate that the 3- to 5-fold therapeutic window for LY411,575 can be
      exploited to obtain reduction in Abeta levels without induction of intestinal
      side effects, that intermittent treatment could be used to mitigate side effects,
      and that a 6-day dosing paradigm can be used to rapidly determine the therapeutic
      window of novel gamma-secretase inhibitors.

PMID- 16946103
TI  - Muscarinic regulation of ether-a-go-go-related gene K+ currents in interstitial
      cells of Cajal.
AB  - The interstitial cells of Cajal (ICC) of the myenteric plexus generate a set of
      currents that evoke a pacemaker potential that sets the initial conditions for
      the contraction frequency and duration of the electrically coupled intestinal
      musculature. The synapse-like contacts between ICC and myenteric motor nerves
      highlight the potential role of the enteric nervous system in regulating the
      pacemaking currents in ICC. The objective of the present study was to investigate
      muscarinic regulation of the ether-a-go-go-related gene (ERG) K(+) current.
      Immunoreactivity of the M(3) receptor (M(3)R) but not the M(2) receptor was
      detected on murine jejunal ICC-Auerbach's plexus (ICC-AP). The muscarinic agonist
      bethanechol reduced hyperpolarization-evoked peak ERG currents at -100 mV by 23
      +/- 1% and increased both fast and slow time constants of deactivation, resulting
      in increased steady-state currents between -55 and -35 mV. Bethanechol also
      increased depolarization-evoked steady-state currents by 59 +/- 10% at -40 mV,
      whereas currents were decreased at potentials positive to 0 mV. The half-maximal
      voltage of activation was shifted 11.9 mV leftward. Interestingly, the time
      constant of activation increased only at -40 mV. Atropine prevented and 2 muM
      E4031 [1-[2-(6-methyl-2-pyridyl)-ethyl-4-(methylsulfonylaminobenzoyl)piperidine]
      inhibited bethanechol-affected currents. The effect of bethanechol was mimicked
      by protein kinase C (PKC) activation and diminished by PKC inhibition. Our
      results indicate that the ERG K(+) channel in ICC is affected by stimulation of
      muscarinic receptors, probably the M(3)R, via a PKC-dependent mechanism.
      Modulation of the ERG K(+) current in ICC-AP will affect the kinetics of
      pacemaking in the intestinal musculature.

PMID- 16946105
TI  - Editorial: nursing and health systems research: hospital systems.

PMID- 16946106
TI  - Unit type differences in RN workgroup job satisfaction.
AB  - Using cross-sectional data from the 2004 National Database of Nursing Quality
      Indicators (NDNQI) RN Satisfaction Survey, differences in RN workgroup job
      satisfaction were examined among 10 unit types--medical-surgical, step-down,
      critical care, pediatric, maternal-newborn, psychiatric, emergency department,
      rehabilitation, surgical services, and outpatient clinics and labs. The national
      sample included RN workgroups in 2,900 patient care units (55,516 RNs; 206
      hospitals in 44 states). Workgroup satisfaction across all unit types was
      moderate. RN workgroups in pediatric units were the most satisfied, whereas those
      in surgical services and emergency department unit types were least satisfied. A
      consistent finding across all unit types was high satisfaction with the specific
      domains of nurse-to-nurse interaction, professional status, and professional
      development versus much lower satisfaction with task, decision making, and pay.
      Findings can be used to inform and develop investigations that examine specific
      aspects of the work environment for RN workgroups in various unit types.

PMID- 16946104
TI  - R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor
      signaling and reduces immune complex-mediated inflammation.
AB  - Recent compelling evidence has lead to renewed interest in the role of antibodies
      and immune complexes in the pathogenesis of several autoimmune disorders, such as
      rheumatoid arthritis. These immune complexes, consisting of autoantibodies to
      self-antigens, can mediate inflammatory responses largely through binding and
      activating the immunoglobulin Fc receptors (FcRs). Using cell-based structure
      activity relationships with cultured human mast cells, we have identified the
      small molecule R406 [N4-(2,2-dimethyl-3-oxo-4H-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2
      (3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine] as a potent inhibitor of
      immunoglobulin E (IgE)- and IgG-mediated activation of Fc receptor signaling
      (EC(50) for degranulation = 56-64 nM). Here we show that the primary target for
      R406 is the spleen tyrosine kinase (Syk), which plays a key role in the signaling
      of activating Fc receptors and the B-cell receptor (BCR). R406 inhibited
      phosphorylation of Syk substrate linker for activation of T cells in mast cells
      and B-cell linker protein/SLP65 in B cells. R406 bound to the ATP binding pocket
      of Syk and inhibited its kinase activity as an ATP-competitive inhibitor (K(i) =
      30 nM). Furthermore, R406 blocked Syk-dependent FcR-mediated activation of
      monocytes/macrophages and neutrophils and BCR-mediated activation of B
      lymphocytes. R406 was selective as assessed using a large panel of Syk
      independent cell-based assays representing both specific and general signaling
      pathways. Consistent with Syk inhibition, oral administration of R406 to mice
      reduced immune complex-mediated inflammation in a reverse-passive Arthus reaction
      and two antibody-induced arthritis models. Finally, we report a first-inhuman
      study showing that R406 is orally bioavailable, achieving exposures capable of
      inhibiting Syk-dependent IgE-mediated basophil activation. Collectively, the
      results show R406 potential for modulating Syk activity in human disease.

PMID- 16946107
TI  - Relationships among teams, culture, safety, and cost outcomes.
AB  - The objective of this study is to test the transtheoretical integration model,
      which proposes relationships among team-based phenomena and patient safety and
      resource-use outcome variables. The sample consisted of 411 nursing staff (n =
      372) and multidisciplinary team members (n = 39) from 16 medical surgical units.
      Staff were surveyed to evaluate their perceptions of hospital culture, work group
      design, and positive and negative team processes. Managers provided data
      concerning outcome variables of patient falls with injury, average length of stay
      (LOS), and labor and supply expenses for their patient care units. A group-type
      hospital culture predicted fewer patient falls with injury; a developmental-type
      hospital culture predicted higher patient care unit costs. Team design and
      processes were predictive of longer LOS for patients on medical-surgical units.
      Conclusions of the study were that hospital contexts external to the patient care
      unit may be important contributors to patient safety and resource use on nursing
      units.

PMID- 16946108
TI  - Are patient falls and pressure ulcers sensitive to nurse staffing?
AB  - Research has demonstrated an association between more nurses and more qualified
      nursing staff in hospitals and better patient outcomes. Patient falls and
      pressure ulcers have been advanced as nursing-sensitive outcomes. This article
      evaluates the state of the science linking nurse staffing to falls and pressure
      ulcers. Studies that employed multivariate analysis to discern the effect of
      nurse staffing on patient falls and pressure ulcers in hospitals were evaluated.
      Eleven studies that met inclusion criteria were contrasted on their data sources
      and measures, data analysis, risk adjustment, and results. The evidence of an
      effect of nursing hours or skill mix on patient falls and pressure ulcers is
      equivocal. Substantial differences in research methods across studies may account
      for the mixed findings. Two study types were identified based on the level at
      which nurse staffing was measured, hospital or nursing unit, which exhibited
      systematic differences in measures and methods. Improvements in measurement and
      methods are suggested.

PMID- 16946109
TI  - Staff nurses and their solutions to the nursing shortage.
AB  - Nurses in acute care hospitals report that situations in their work setting and
      profession are in dire need of repair. Although they waiver on their intention to
      remain in their institution and nursing, they do not waiver on their selected
      resolution to nursing's shortage. A total of 787 staff nurses in eight
      geographically and demographically diverse states responded and were asked to
      select the "Top 5" actions they thought would improve nursing and decrease the
      shortage. Creating career ladders was endorsed by most respondents (85%) with
      increasing pay endorsed by the fewest (33%). When selecting the single most
      important action, they reversed the order--increased pay was the most endorsed
      (26%), and creating career ladders and increased educational opportunities were
      endorsed by less than 1%. Nurses appeared to be concerned about the profession in
      general; however, when asked the "most important" thing to do, an age-old action
      was selected--increase pay.

PMID- 16946110
TI  - Methodological issues in nurse staffing research.
AB  - The purpose of this article is to identify and describe four issues in nurse
      staffing research that must be addressed before the evidence base for the
      relationship between nurse staffing and quality of care can be said to be
      theoretically and empirically sufficient. The issues are the need to build well
      developed theory, use valid and reliable databases, appropriate risk-adjustment
      systems, and address issues of causal inference in nonexperimental research.

PMID- 16946111
TI  - Teaching and community hospital work environments.
AB  - The Institute of Medicine report suggests that nursing work environments
      experience threats to patient safety related to organizational management and
      workforce deployment practices, work design, and organizational culture.
      Organizational factors contribute to nursing and potentially patient outcomes,
      yet few studies have examined the differences in practices perceived by nurses
      employed in different settings. Nurses from 16 medical and surgical units in
      eight randomly selected acute care hospitals representing teaching and community
      organizations participated in this project. Nurses working in teaching hospitals
      reported lower levels of role tension, yet their perceptions of the quality of
      work, the work environment, nursing unit leadership, quality of care, and levels
      of job stress and job satisfaction were higher than their colleagues in the
      community sites. This study highlights some important differences between
      teaching and community hospitals that can inform nurse executives and policy
      makers of the unique work-life issues for different groups of nurses.

PMID- 16946112
TI  - Hospital demand for licensed practical nurses.
AB  - Despite evidence that hospital use of licensed practical nurses (LPNs) declined
      in the 1990s, the current registered nurse (RN) shortage has prompted interest in
      LPNs as substitutes for RNs. Hospitals, being the dominant employer of RNs, have
      an economic incentive to use less expensive LPNs as substitutes. Beside wages,
      there are several forces underlying hospital demand for LPNs. In this article,
      the authors model and estimate hospital demand for LPNs as a function of nurse
      wages and hospital, market, and patient characteristics using a longitudinal data
      set of short-term general hospitals in the United States. The authors find
      evidence that higher RN wages increase hospital demand for LPNs, both in levels
      and relative to RNs, suggesting that hospitals at least partially substitute RNs
      with LPNs.

PMID- 16946114
TI  - Cherishing the past: 100 years of nursing education at the American University of
      Beirut.
AB  - This article describes the foundation and the development of nursing education at
      the American University of Beirut, the first professional school in the country
      and the region, across 100 years (1905-2005). It talks about the early years,
      pioneering achievements (1905-1940), the school's leadership in nursing from 1940
      to 1976, the war years from 1976 to 1993, and postwar global vision (1993-2005).
      Furthermore, it gives special tribute to the dedication and hard work of the
      founders, Ms. Jane Elizabeth Van Zandt and Ms. Mary Bliss Dale, and all the
      directors whose endeavors and wisdom have helped the development of the school
      from diploma to bachelor and master's programs.

PMID- 16946115
TI  - Exposure to war-related traumatic events, prevalence of PTSD, and general
      psychiatric morbidity in a civilian population from Southern Lebanon.
AB  - The South of Lebanon has experienced prolonged armed conflict. The current study
      aims to investigate the degree of exposure to traumatic events and prevalence of
      posttraumatic stress disorder (PTSD) and nonspecific general psychiatric
      morbidity in a civilian population from the South of Lebanon. The design was
      cross-sectional with random sampling. War-related traumatic events and symptoms
      of PTSD were assessed by the Harvard Trauma Questionnaire and general psychiatric
      morbidity by the General Health Questionnaire (GHQ-28). Almost all participants,
      97.7%, had experienced, witnessed, or heard of a war-related traumatic event.
      Current PTSD prevalence was 29.3%. PTSD symptoms correlated highly with GHQ-28
      symptoms, r = .73 (p < .0001). The present study indicates a need for
      psychological interventions in the population and studies to assess such
      interventions.

PMID- 16946116
TI  - Delay in seeking health care for acute coronary syndromes in a Lebanese sample.
AB  - Early treatment of patients with acute coronary syndromes (ACS) is crucial to
      reduce morbidity and mortality. The purpose of this study was to examine delay in
      seeking care for ACS symptoms in a Lebanese sample and identify predictors of
      delay. Medical record reviews and interviews using the Response to Symptoms
      Questionnaire were conducted with 204 ACS patients in coronary care within 72
      hours of admission. Median time from symptom onset to hospital arrival was 4.5
      hours. Higher education, presence of dyspnea, intermittent symptoms, and waiting
      for symptoms to go away predicted longer delays, whereas intensity of symptoms
      and active response (going to the hospital) predicted shorter delays. The
      findings suggest lack of knowledge of ACS symptoms and the need for public
      education in this regard.

PMID- 16946117
TI  - Cognitive appraisal of stress and health status of wage working and non-wage
      working women in Jordan.
AB  - This cross-sectional correlation study addresses the stress appraisal of 93
      Jordanian wage working and non-wage working single and married women in Jordan
      and the relationship of appraised stress to their physical and psychological
      health. Data were collected using a demographic interview guide that included a
      Likert-type scale addressing perceived global social stress, the Cornell Medical
      Index (CMI), and the Perceived Stress Scale (PSS). Perceived stress had no
      significant relations with physical and emotional health as measured by the PSS,
      but significant relations were found between social stress and indicators of
      health. In fact, social stress was the single most significant predictor of
      overall health, physical health, and emotional health. The findings on the health
      profile of participants and social stress have important implications for future
      research and for illness prevention and health promotion initiatives.

PMID- 16946118
TI  - Raising awareness and providing free screening improves cervical cancer screening
      among economically disadvantaged Lebanese/Armenian women.
AB  - Women need to practice cervical screening regularly to reduce morbidity and
      mortality. The purpose of this study was to examine the impact of an intervention
      program on knowledge, attitude, and practice of cervical screening in the
      population of Lebanese/Armenian women. The design was a cross-sectional, quasi
      experimental posttest survey following a year long intervention program. The
      sample included 176 women, who were members of the Armenian Relief Cross in
      Lebanon. Interventions consisted of educational classes, media messages, and free
      screening. The instrument was a self-administered questionnaire. Knowledge of
      women with intervention was higher (p > .05) and practice rate increased between
      intervention and comparison groups. No difference in attitude was noted. The
      study was successful in raising awareness and increasing screening in the sample.
      It is recommended to continue helping women to overcome barriers for cervical
      screening.

PMID- 16946119
TI  - Utilization of family planning services in the Governorate of Zarqa, Jordan.
AB  - Quantitative and qualitative methods are used to explore family planning (FP)
      utilization in four clinics with different models of provision in Zarqa
      Governorate in Jordan. Constraints to utilization at the service level are
      identified based on service observations and the perspectives of providers.
      Service statistics, clinic observations, and focus group discussions were used to
      compare utilization patterns and to evaluate the strengths and weaknesses of the
      different models of provision. Findings show that FP provision is still
      fragmented and "techno-patriarchal" in Jordan. Strengthening coordination
      mechanisms between the service sectors and addressing men are important
      strategies to increase FP utilization that are transferable to other countries of
      the Middle East and the developing world.

PMID- 16946120
TI  - The adaptation of mothers of children with intellectual disability in Lebanon.
AB  - In many Middle Eastern countries, including Lebanon, there is a stigma attached
      to families who have an intellectually impaired child. These families complain of
      isolation and lack of community resources that could help them cope with their
      circumstances to optimize the child's abilities. Health professionals and
      researchers should be cognizant of factors related to the process of stress
      adaptation to help families cope with their circumstances. The aim of this cross
      sectional study was to identify factors that play a role in mothers' adaptation
      to the care of their intellectually impaired children. The results, based on a
      sample of 127 mothers from Lebanon, reveal that a high percentage of mothers had
      depressive symptoms. Multiple regression analysis demonstrates that by order of
      importance, the factors that determine maternal depression are family strain,
      parental stress, and family income. The conclusions about nursing implications
      from a cultural perspective are discussed and recommendations proposed.

PMID- 16946121
TI  - End-of-life practices at a Lebanese hospital: courage or knowledge?
AB  - End-of-life care requires knowledgeable and culturally sensitive clinicians to
      assist patients and families dealing with the difficult journey of death. The
      authors present important end-of-life considerations for health care providers
      dealing with culturally diversified patients. A case study approach is used
      illustrating two case vignettes derived from the practice of an intensive care
      setting of a tertiary teaching facility in a large urban area in Lebanon. In a
      multidisciplinary fashion, practices of end of life were explored and a protocol
      developed to guide health care providers. Special cultural values were identified
      such as importance of family involvement and religious beliefs. Implications for
      practice are described.

PMID- 16946122
TI  - Cultural attitudes and beliefs about pain.
AB  - Patients and health professionals bring their own cultural attitudes to the
      communication and interpretation of the patient's pain experience. In this
      interaction, it is the health professional's knowledge and attitudes that
      dominate the response to the patient's experience of pain. In Saudi Arabia, a
      multicultural foreign and local health care team is challenged to understand the
      cultural beliefs and attitudes toward pain of both patients and team members. To
      increase cultural understanding and knowledge, a collaborative inquiry project
      using a culturally diverse group was conducted to learn about cultural attitudes
      and beliefs on the causes, treatment, and experience of pain. This article
      presents the knowledge gained from the collaborative inquiry journey of action
      and reflection.

PMID- 16946123
TI  - Improving global health care through diversity.
AB  - One of the major challenges facing the nursing profession is the globalization of
      nursing education, research, and practice. The word diversity is derived from the
      Latin word divertere meaning being different or having differences. Diversity in
      nursing practice means providing competent care to clients from different
      cultures, conducting research in multi-cultural settings, and implementing
      educational programs to diverse populations. Key principles and practices that
      provide a framework for diverse relationships in nursing practice, research, and
      education must be driven by a professional commitment in building a global
      community that is inclusive, respectful, and dedicated to global health care for
      all. Through international collaborations and individual and collective
      partnerships, nurses can build bridges between and among national health care
      systems, strengthen the international health care infrastructure, broaden health
      care delivery systems, and improve the quality of health care for all.

PMID- 16946124
TI  - Perspectives of an American University of Beirut graduate on nursing scholarship.
AB  - Nursing scholarship is necessary for the advancement of the nursing discipline.
      Engaging in scholarly activities is every nurse's responsibility regardless of
      job title, position, or practice setting. Scholarship today is no longer limited
      to the practice of academicians and scientists; rather, it is integral to the
      work of nurse leaders, clinicians, health policy specialists, researchers, and
      educators. The scholarly contributions of nurses have been noted at regional,
      national, even international levels. This article describes a renewed and
      contemporary view on nursing scholarship and discusses the role of the nurse in
      promoting the nursing profession using scholarly activities.

PMID- 16946125
TI  - Magnetic resonance imaging of uneven pulmonary perfusion in hypoxia in humans.
AB  - RATIONALE: Inhomogeneous hypoxic pulmonary vasoconstriction causing regional
      overperfusion and high capillary pressure is postulated for explaining how high
      pulmonary artery pressure leads to high-altitude pulmonary edema in susceptible
      (HAPE-S) individuals. OBJECTIVE: Because different species of animals also show
      inhomogeneous hypoxic pulmonary vasoconstriction, we hypothesized that
      inhomogeneity of lung perfusion in general increases in hypoxia, but is more
      pronounced in HAPE-S. For best temporal and spatial resolution, regional
      pulmonary perfusion was assessed by dynamic contrast-enhanced magnetic resonance
      imaging. METHODS: Dynamic contrast-enhanced magnetic resonance imaging and
      echocardiography were performed during normoxia and after 2 h of hypoxia (Fi(O2)
      = 0.12) in 11 HAPE-S individuals and 10 control subjects. As a measure for
      perfusion inhomogeneity, the coefficient of variation for two perfusion
      parameters (peak signal intensity, time-to-peak) was determined for the whole
      lung and isogravitational slices. RESULTS: There were no differences in perfusion
      inhomogeneity between the groups in normoxia. In hypoxia, analysis of
      coefficients of variation indicated a greater inhomogeneity in all subjects,
      which was more pronounced in HAPE-S compared with control subjects.
      Discrimination between HAPE-S and control subjects was best in gravity-dependent
      lung areas. Pulmonary artery pressure during hypoxia increased from 22 +/- 3 to
      53 +/- 9 mm Hg in HAPE-S and 24 +/- 4 to 33 +/- 6 mm Hg in control subjects (mean
      +/- SD; p < 0.001), respectively. CONCLUSION: This study shows that hypoxic
      pulmonary vasoconstriction is inhomogeneous in hypoxia in humans, particularly in
      HAPE-S individuals where it is accompanied by a greater increase in pulmonary
      artery pressure compared with control subjects. These findings support the
      hypothesis of exaggerated and uneven hypoxic pulmonary vasoconstriction in HAPE-S
      individuals.

PMID- 16946126
TI  - Health effects of the 2003 Southern California wildfires on children.
AB  - RATIONALE: In late October 2003, Southern California wildfires burned more than
      3,000 km2. The wildfires produced heavy smoke that affected several communities
      participating in the University of Southern California Children's Health Study
      (CHS). OBJECTIVES: To study the acute effects of fire smoke on the health of CHS
      participants. METHODS: A questionnaire was used to assess smoke exposure and
      occurrence of symptoms among CHS high-school students (n = 873; age, 17-18 yr)
      and elementary-school children (n = 5,551; age, 6-7 yr), in a total of 16
      communities. Estimates of particulate matter (PM10) concentrations during the 5 d
      with the highest fire activity were used to characterize community smoke level.
      MAIN RESULTS: All symptoms (nose, eyes, and throat irritations; cough;
      bronchitis; cold; wheezing; asthma attacks), medication usage, and physician
      visits were associated with individually reported exposure differences within
      communities. Risks increased monotonically with the number of reported smoky
      days. For most outcomes, reporting rates between communities were also associated
      with the fire-related PM10 levels. Associations tended to be strongest among
      those without asthma. Individuals with asthma were more likely to take preventive
      action, such as wearing masks or staying indoors during the fire. CONCLUSIONS:
      Exposure to wildfire smoke was associated with increased eye and respiratory
      symptoms, medication use, and physician visits.

PMID- 16946127
TI  - Randomized study of adding inhaled iloprost to existing bosentan in pulmonary
      arterial hypertension.
AB  - RATIONALE: Small, open-label studies suggest that combinations of existing
      therapies may be effective for pulmonary arterial hypertension (PAH). OBJECTIVE:
      To evaluate the safety and efficacy of adding inhaled iloprost, a prostacyclin
      analog, to the endothelin receptor antagonist bosentan in patients with PAH.
      METHODS: In a randomized, multicenter, double-blind trial, inhaled iloprost (5
      mug) or placebo was added to stable monotherapy with bosentan for 12 wk. Efficacy
      endpoints included change from baseline in 6-min-walk distance (6-MWD), modified
      New York Heart Association (NYHA) functional class, hemodynamic parameters, and
      time to clinical worsening. MEASUREMENTS AND MAIN RESULTS: A total of 67 patients
      with PAH (55% idiopathic PAH, 45% associated PAH, 94% NYHA class III, and mean
      baseline 6-MWD of 335 m) were randomized. At Week 12, patients receiving iloprost
      had a mean increase in 6-MWD of 30 m (p = 0.001); placebo patients had a mean 6
      MWD increase of 4 m (p = 0.69), with a placebo-adjusted difference of +26 m (p =
      0.051). NYHA status improved by one class in 34% of iloprost versus 6% of placebo
      patients (p = 0.002). Iloprost delayed the time to clinical worsening (p =
      0.0219). Improvements were noted in postinhalation placebo-adjusted change in
      mean pulmonary artery pressure (-8 mm Hg; p < 0.001) and pulmonary vascular
      resistance (-254 dyn x s x cm(-5); p < 0.001). Combination therapy was well
      tolerated. CONCLUSIONS: Within the limitations of a relatively small sample size,
      results of this study demonstrate that the addition of inhaled iloprost in
      patients with PAH with reduced exercise capacity on bosentan monotherapy is safe
      and efficacious.

PMID- 16946129
TI  - Increased ratio of CD31+/CD42- microparticles to endothelial progenitors as a
      novel marker of atherosclerosis in hypercholesterolemia.
AB  - OBJECTIVE: Atherosclerosis may be caused by increased endothelial damage and by a
      consumptive loss of endothelial repair capacity by endothelial progenitors.
      Arterial stiffness is a reliable marker of atherosclerosis and a positive
      correlate of endothelial damage. We investigated whether an increased ratio of
      CD31+/CD42- microparticles to endothelial progenitors, a possible indicator of
      endothelial damage and impaired endothelium reparation, may contribute to aortic
      stiffness in hypercholesterolemia. We also studied the in vitro effect of
      microparticles from hypercholesterolemic patients on endothelial progenitor
      survival. METHODS AND RESULTS: Circulating CD31+/CD42- microparticles,
      endothelial progenitors, and aortic pulse wave velocity (aPWV), a measure of
      aortic stiffness, were measured in 50 patients with never-treated
      hypercholesterolemia and 50 normocholesterolemic controls. Hypercholesterolemic
      patients had more circulating CD31+/CD42- microparticles, less endothelial
      progenitors, and a stiffer aorta than controls. aPWV was associated with
      CD31+/CD42- microparticles (r=0.61; P<0.001), endothelial progenitors (r=-0.45,
      P<0.001), and with cholesterol levels (r=0.51; P<0.001). High plasma cholesterol
      and a high ratio of CD31+/CD42- microparticles to endothelial progenitors
      independently predicted an increased aPWV. Microparticles from
      hypercholesterolemic patients caused a significant endothelial progenitor loss in
      vitro. CONCLUSIONS: Hypercholesterolemia-related aortic stiffness is promoted by
      plasma cholesterol directly, increased endothelial damage, and reduced
      endothelium repair capacity by endothelial progenitors.

PMID- 16946128
TI  - p53 mediates particulate matter-induced alveolar epithelial cell mitochondria
      regulated apoptosis.
AB  - RATIONALE: Exposure to particulate matter (PM) causes lung cancer by mechanisms
      that are unknown, but p53 dysfunction is implicated. OBJECTIVE: We determined
      whether p53 is required for PM-induced apoptosis in both human and rodent
      alveolar type (AT) 2 cells. METHODS: A well-characterized form of urban PM was
      used to determine whether it induces mitochondrial dysfunction (mitochondrial
      membrane potential change [DeltaPsi m] and caspase-9 activation), p53 protein and
      mRNA expression, and apoptosis (DNA fragmentation and annexin V staining) in
      vitro using A549 cells and primary isolated human and rat AT2 cells. The role of
      p53 was assessed using inhibitors of p53-dependent transcription, pifithrin
      alpha, and a genetic approach (overexpressing E6 or dominant negative p53). In
      mice, the in vivo effects of PM causing p53 expression and apoptosis were
      assessed 72 h after a single PM intratracheal instillation. MEASUREMENTS AND MAIN
      RESULTS: PM-induced apoptosis in A549 cells was characterized by increased p53
      mRNA and protein expression, mitochondrial translocation of Bax and p53, a
      reduction in DeltaPsi m, and caspase-9 activation, and these effects were blocked
      by inhibiting p53-dependent transcription. Similar findings were noted in primary
      isolated human and rat AT2 cells. A549-rho degrees cells that are incapable of
      mitochondrial reactive oxygen species production were protected against PM
      induced DeltaPsi m, p53 expression, and apoptosis. In mice, PM induced p53
      expression and apoptosis at the bronchoalveolar duct junctions. CONCLUSIONS:
      These data suggest a novel interaction between p53 and the mitochondria in
      mediating PM-induced apoptosis that is relevant to the pathogenesis of lung
      cancer from air pollution.

PMID- 16946130
TI  - Cholesteryl ester transfer protein decreases high-density lipoprotein and
      severely aggravates atherosclerosis in APOE*3-Leiden mice.
AB  - OBJECTIVE: The role of cholesteryl ester transfer protein (CETP) in the
      development of atherosclerosis is still undergoing debate. Therefore, we
      evaluated the effect of human CETP expression on atherosclerosis in APOE*3-Leiden
      (E3L) mice with a humanized lipoprotein profile. METHODS AND RESULTS: E3L mice
      were crossbred with human CETP transgenic mice. On a chow diet, CETP expression
      increased plasma total cholesterol (TC) (+43%; P<0.05). To evaluate the effects
      of CETP on the development of atherosclerosis, mice were fed a Western-type diet
      containing 0.25% cholesterol, leading to 4.3-fold elevated TC levels in both E3L
      and CETP.E3L mice (P<0.01). On both diets, CETP expression shifted the
      distribution of cholesterol from high-density lipoprotein (HDL) toward very-low
      density lipoprotein (VLDL)/low-density lipoprotein (LDL). Moreover, plasma of
      CETP.E3L mice had reduced capacity (-39%; P<0.05) to induce SR-BI-mediated
      cholesterol efflux from Fu5AH cells than plasma of E3L mice. After 19 weeks on
      the Western-type diet, CETP.E3L mice showed a 7.0-fold increased atherosclerotic
      lesion area in the aortic root compared with E3L mice (P<0.0001). CONCLUSIONS:
      CETP expression in E3L mice shifts the distribution of cholesterol from HDL to
      VLDL/LDL, reduces plasma-mediated SR-BI-dependent cholesterol efflux, and
      represents a clear pro-atherogenic factor in E3L mice. We anticipate that the
      CETP.E3L mouse will be a valuable model for the preclinical evaluation of HDL
      raising interventions on atherosclerosis development.

PMID- 16946131
TI  - Tetrahydrobiopterin and cardiovascular disease.
AB  - Tetrahydrobiopterin (BH4) is an essential cofactor for the aromatic amino acid
      hydroxylases, which are essential in the formation of neurotransmitters, and for
      nitric oxide synthase. It is presently used clinically to treat some forms of
      phenylketonuria (PKU) that can be ameliorated by BH4 supplementation. Recent
      evidence supports potential cardiovascular benefits from BH4 replacement for the
      treatment of hypertension, ischemia-reperfusion injury, and cardiac hypertrophy
      with chamber remodeling. Such disorders exhibit BH4 depletion because of its
      oxidation and/or reduced synthesis, which can result in functional uncoupling of
      nitric oxide synthase (NOS). Uncoupled NOS generates more oxygen free radicals
      and less nitric oxide, shifting the nitroso-redox balance and having adverse
      consequences on the cardiovascular system. While previously difficult to use as a
      treatment because of chemical instability and cost, newer methods to synthesize
      stable BH4 suggest its novel potential as a therapeutic agent. This review
      discusses the biochemistry, physiology, and evolving therapeutic potential of BH4
      for cardiovascular disease.

PMID- 16946132
TI  - Tissue-specific induction of intestinal ABCA1 expression with a liver X receptor
      agonist raises plasma HDL cholesterol levels.
AB  - ABCA1 controls the rate-limiting step in HDL particle formation and is therefore
      an attractive molecular target for raising HDL levels and protecting against
      atherosclerosis. Intestinal ABCA1 significantly and independently contributes to
      plasma HDL cholesterol levels in mice, suggesting that induction of intestinal
      ABCA1 expression may raise plasma HDL cholesterol levels. We evaluated the
      ability of a synthetic Liver X Receptor (LXR) agonist, GW3965, to raise plasma
      HDL cholesterol levels in control mice and mice with liver- or intestinal
      specific deletion of the Abca1 gene. Oral treatment with GW3965 increased the
      expression of ABCA1 by approximately 6-fold (P=0.004) as well as other LXR target
      genes in the intestines of mice, with no change in the hepatic expression of
      these genes. This resulted in a significant approximately 48% elevation of plasma
      HDL cholesterol levels in wild-type mice (P<0.01) with no change in plasma
      triglycerides. A similar increase in HDL cholesterol was observed in mice lacking
      hepatic ABCA1, indicating that the increase in plasma HDL cholesterol was
      independent of hepatic ABCA1. This effect was completely abrogated in mice
      lacking intestinal ABCA1. These data indicate that intestinal ABCA1 may be an
      attractive therapeutic target for raising HDL levels while avoiding the hepatic
      lipogenesis and hypertriglyceridemia typical of systemic LXR activation.

PMID- 16946133
TI  - Maternal immunization programs postnatal immune responses and reduces
      atherosclerosis in offspring.
AB  - Maternal hypercholesterolemia during pregnancy increases offspring susceptibility
      to atherosclerosis by an oxidation-dependent mechanism. The present studies
      investigated whether maternal immunization with oxidized LDL (OxLDL) before
      pregnancy protects the fetus from atherogenic in utero programming by maternal
      hypercholesterolemia. Maternal immunization of NZW rabbits and LDL receptor
      deficient mice indeed reduced atherosclerosis in adult offspring by up to 56%,
      but the protective effect could not be attributed to a reduction of fetal
      exposure to hypercholesterolemia alone, and even nonspecific immune stimulation
      with adjuvant only provided some protection. Unexpectedly, offspring of immunized
      mothers developed increased IgM antibodies to selective OxLDL epitopes and
      increased IgM-LDL immune complexes, compared with offspring of nonimmunized
      controls. Even naive offspring of OxLDL-immunized mothers never exposed to
      postnatal hypercholesterolemia responded to a one-time OxLDL and KLH challenge
      with greater OxLDL-specific IgM responses, increased OxLDL-specific IgM-secreting
      B cells, and more IgM-LDL immune complexes. In contrast, maternal immunization
      with KLH, a T cell-dependent nonmammalian antigen, did not influence postnatal
      immune responses. Effects of maternal OxLDL-immunization on offspring B cells and
      selective antibodies were independent of transplacental passage of maternal
      immunoglobulins. Results show that maternal immunization with antigens prevalent
      in atherosclerotic lesions reduces atherogenesis in their offspring by mechanisms
      that include, but are not limited to, reduced fetal exposure to maternal
      hypercholesterolemia and lipid peroxidation. More importantly, they demonstrate
      in principle that maternal adaptive immunity to selective antigens influences
      postnatal B cell and antibody responses in offspring, and that modulation of in
      utero immune programming may influence immune-modulated diseases later in life.

PMID- 16946134
TI  - Cardiac alternans do not rely on diastolic sarcoplasmic reticulum calcium content
      fluctuations.
AB  - Cardiac alternans are thought to be a precursor to life-threatening arrhythmias.
      Previous studies suggested that alterations in sarcoplasmic reticulum (SR) Ca2+
      content are either causative or not associated with myocyte Ca2+ alternans.
      However, those studies used indirect measures of SR Ca2+. Here we used direct
      continuous measurement of intra-SR free [Ca2+] ([Ca2+]SR) (using Fluo5N) during
      frequency-dependent Ca2+ alternans in rabbit ventricular myocytes. We tested the
      hypothesis that alternating [Ca2+]SR is required for Ca2+ alternans. Amplitudes
      of [Ca2+]SR depletions alternated in phase with cytosolic Ca2+ transients and
      contractions. Some cells showed clear alternation in diastolic [Ca2+]SR during
      alternans, with higher [Ca2+]SR before the larger SR Ca2+ releases. However, the
      extent of SR Ca2+ release during the small beats was smaller than expected for
      the modest decrease in [Ca2+]SR. In other cells, clear Ca2+ alternans was
      observed without alternations in diastolic [Ca2+]SR. Additionally, alternating
      cells were observed, in which diastolic [Ca2+]SR fluctuations occurred
      interspersed by depletions in which the amplitude was unrelated to the preceding
      diastolic [Ca2+]SR. In all forms of alternans, the SR Ca2+ release rate was
      higher during large depletions than during small depletions. Although [Ca2+]SR
      exerts major influence on SR Ca2+ release, alternations in [Ca2+](SR) are not
      required for Ca2+ alternans to occur. Rather, it seems likely that some other
      factor, such as ryanodine receptor availability after a prior beat (eg, recovery
      from inactivation), is of greater importance in initiating frequency-induced Ca2+
      alternans. However, once such a weak SR Ca2+ release occurs, it can result in
      increased [Ca2+]SR and further enhance SR Ca2+ release at the next beat. In this
      way, diastolic [Ca2+]SR alternans can enhance frequency-induced Ca2+ alternans,
      even if they initiate by other means.

PMID- 16946136
TI  - Direct evidence for endothelial vascular endothelial growth factor receptor-1
      function in nitric oxide-mediated angiogenesis.
AB  - Vascular endothelial growth factor-A (VEGF) is critical for angiogenesis but
      fails to induce neovascularization in ischemic tissue lesions in mice lacking
      endothelial nitric oxide synthase (eNOS). VEGF receptor-2 (VEGFR-2) is critical
      for angiogenesis, although little is known about the precise role of endothelial
      VEGFR-1 and its downstream effectors in this process. Here we have used a
      chimeric receptor approach in which the extracellular domain of the epidermal
      growth factor receptor was substituted for that of VEGFR-1 (EGLT) or VEGFR-2
      (EGDR) and transduced into primary cultures of human umbilical vein endothelial
      cells (HUVECs) using a retroviral system. Activation of HUVECs expressing EGLT or
      EGDR induced rapid phosphorylation of eNOS at Ser1177, release of NO, and
      formation of capillary networks, similar to VEGF. Activation of eNOS by VEGFR-1
      was dependent on Tyr794 and was mediated via phosphatidylinositol 3-kinase,
      whereas VEGFR-2 Tyr951 was involved in eNOS activation via phospholipase Cgamma1.
      Consistent with these findings, the VEGFR-1-specific ligand placenta growth
      factor-1 activated phosphatidylinositol 3-kinase and VEGF-E, which is selective
      for VEGFR-2-activated phospholipase Cgamma1. Both VEGFR-1 and VEGFR-2 signal
      pathways converged on Akt, as dominant-negative Akt inhibited the NO release and
      in vitro tube formation induced following activation of EGLT and EGDR. The
      identification Tyr794 of VEGFR-1 as a key residue in this process provides direct
      evidence of endothelial VEGFR-1 in NO-driven in vitro angiogenesis. These studies
      provide new sites of modulation in VEGF-mediated vascular morphogenesis and
      highlight new therapeutic targets for management of vascular diseases.

PMID- 16946135
TI  - Proteomic analysis of pharmacological preconditioning: novel protein targets
      converge to mitochondrial metabolism pathways.
AB  - Ischemic preconditioning is characterized by resistance to ischemia reperfusion
      injury in response to previous short ischemic episodes, a protective effect that
      can be mimicked pharmacologically. The underlying mechanism of protection remains
      controversial and requires greater understanding before it can be fully exploited
      therapeutically. To investigate the overall effect of preconditioning on the
      myocardial proteome, isolated rabbit ventricular myocytes were treated with drugs
      known to induce preconditioning, adenosine or diazoxide (each at 100 micromol/L
      for 60 minutes). Their protein profiles were then compared with vehicle-treated
      controls (n=4 animals per treatment) using a multitiered 2D gel electrophoresis
      approach. Of 28 significantly altered protein spots, 19 nonredundant proteins
      were identified (5 spots remained unidentified). The majority of these proteins
      are involved in mitochondrial energetics, including subunits of tricarboxylic
      acid cycle enzymes and oxidative phosphorylation complexes. These changes were
      not indiscriminate, with only a small number of enzymes or complex subunits
      altered, indicating a very specific and targeted affect of these 2
      preconditioning mimetics. Among the changes were shifts in the extent of
      posttranslational modification of 4 proteins. One of these, the adenosine-induced
      phosphorylation of the ATP synthase beta subunit, was fully characterized with
      the identification of 5 novel phosphorylation sites. This proteomics approach
      provides an overall assessment of the cellular response to pharmacological
      treatment with adenosine and diazoxide and identifies a distinct subset of
      enzymes and protein complex subunit that may underlie the preconditioned
      phenotype.

PMID- 16946137
TI  - Reduced cardiac L-type Ca2+ current in Ca(V)beta2-/- embryos impairs cardiac
      development and contraction with secondary defects in vascular maturation.
AB  - Cardiac myocyte contraction depends on transmembrane L-type Ca2+ currents and the
      ensuing release of Ca2+ from the sarcoplasmic reticulum. Here we show that these
      L-type Ca2+ currents are essential for cardiac pump function in the mouse at
      developmental stages where the functional significance of the heart becomes
      imperative to blood flow and to the continuing growth and survival of the embryo.
      Disruption of the Ca(V)beta2 gene, which encodes for the predominant ancillary
      beta subunit of cardiac Ca2+ channels, resulted in diminished L-type Ca2+
      currents in cardiomyocytes of embryonic day 9.5 (E9.5). This led to a
      functionally compromised heart, causing defective remodeling of intra- and
      extraembryonic blood vessels and embryonic death following E10.5. The defects in
      vascular remodeling were also observed when the Ca(V)beta2 gene was selectively
      targeted in cardiomyocytes, demonstrating that they are secondary to cardiac
      failure rather than a result of the lack of Ca(V)beta2 proteins in the
      vasculature. Partial rescue of the Ca2+ channel currents by a Ca2+ channel
      agonist significantly postponed embryonic death in Ca(V)beta2-/- mice. Taken
      together, these data strongly support the essential role of L-type Ca2+ channel
      activity in cardiomyocytes for normal heart development and function and that
      this is a prerequisite for proper maturation of the vasculature.

PMID- 16946138
TI  - Molecular pH Probes: mediators of angina and ischemic preconditioning?

PMID- 16946139
TI  - Inflame my heart (by p38-MAPK).

PMID- 16946140
TI  - Estrogen and different aspects of vascular disease in women and men.

PMID- 16946141
TI  - Realizing its potential: the intermediate conductance Ca2+-activated K+ channel
      (KCa3.1) and the regulation of blood pressure.

PMID- 16946142
TI  - Toward solving the riddle: the enigma becomes less mysterious.

PMID- 16946143
TI  - NXY-059 for acute ischemic stroke: the promise of neuroprotection is finally
      realized?

PMID- 16946144
TI  - Blood pressure changes during the initial week after different subtypes of
      ischemic stroke.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to clarify the differences
      in the acute blood pressure course among different ischemic stroke subtypes.
      METHODS: We divided 588 consecutive patients with acute brain infarction into
      four clinical subgroups to study the blood pressure levels during the initial 6
      hospital days. RESULTS: During the 6 days, systolic blood pressure of lacunar and
      atherothrombotic patients was higher (P=0.0001) and diastolic blood pressure of
      lacunar patients was higher (P=0.0371) than of patients with the other subtypes.
      Preexisting hypertension was associated with elevated acute systolic blood
      pressure in all patients and in each subtype and with elevated acute diastolic
      blood pressure in all patients, cardioembolic patients, and patients with stroke
      of other etiology. After adjustment by preexisting hypertension, diabetes
      mellitus with a hemoglobin A1c >7.0% was associated with elevated systolic blood
      pressure in all, lacunar, and cardioembolic patients and with diastolic blood
      pressure in all patients. CONCLUSIONS: Blood pressure course of patients
      sustaining acute stroke varied widely according to stroke subtypes. Poorly
      controlled diabetes mellitus, as well as preexisting hypertension, appeared to
      influence blood pressure during the initial week of stroke.

PMID- 16946145
TI  - Low-level laser therapy applied transcranially to rats after induction of stroke
      significantly reduces long-term neurological deficits.
AB  - BACKGROUND AND PURPOSE: Low-level laser therapy (LLLT) modulates various
      biological processes. In the present study, we assessed the hypothesis that LLLT
      after induction of stroke may have a beneficial effect on ischemic brain tissue.
      METHODS: Two sets of experiments were performed. Stroke was induced in rats by
      (1) permanent occlusion of the middle cerebral artery through a craniotomy or (2)
      insertion of a filament. After induction of stroke, a battery of neurological and
      functional tests (neurological score, adhesive removal) was performed. Four and
      24 hours poststroke, a Ga-As diode laser was used transcranially to illuminate
      the hemisphere contralateral to the stroke at a power density of 7.5 mW/cm2.
      RESULTS: In both models of stroke, LLLT significantly reduced neurological
      deficits when applied 24 hours poststroke. Application of the laser at 4 hours
      poststroke did not affect the neurological outcome of the stroke-induced rats as
      compared with controls. There was no statistically significant difference in the
      stroke lesion area between control and laser-irradiated rats. The number of newly
      formed neuronal cells, assessed by double immunoreactivity to bromodeoxyuridine
      and tubulin isotype III as well as migrating cells (doublecortin immunoactivity),
      was significantly elevated in the subventricular zone of the hemisphere
      ipsilateral to the induction of stroke when treated by LLLT. CONCLUSIONS: Our
      data suggest that a noninvasive intervention of LLLT issued 24 hours after acute
      stroke may provide a significant functional benefit with an underlying mechanism
      possibly being induction of neurogenesis.

PMID- 16946146
TI  - The unchanging incidence and case-fatality of stroke in the 1990s: a population
      based study.
AB  - BACKGROUND AND PURPOSE: Many advances were made in stroke prevention strategies
      during the 1990s, and yet temporal trends in stroke incidence and case-fatality
      have not been reported in the United States. Blacks have a 2-fold higher risk of
      stroke; however, there are no data over time showing if any progress has been
      made in reducing racial disparity in stroke incidence. The objective of this
      study was to examine temporal trends in stroke incidence and case-fatality within
      a large, biracial population during the 1990s. METHODS: Within a biracial
      population of 1.3 million, all strokes were ascertained at all local hospitals
      using International Classification of Diseases, 9th Revision codes during July
      1993 to June 1994 and again in 1999. A sampling scheme was used to ascertain
      cases in the out-of-hospital setting. Race-specific incidence and case-fatality
      rates were calculated and standardized to the 2000 US Census population. A
      population-based telephone survey regarding stroke risk factor prevalence and
      medication use was performed in 1995 and 2000. RESULTS: There were 1954 first
      ever strokes in 1993-1994 and 2063 first-ever strokes in 1999. The annual
      incidence of first-ever hospitalized stroke did not significantly change between
      study periods: 158 per 100,000 in both 1993-1994 and 1999 (P=0.97). Blacks
      continue to have higher stroke incidence than whites, especially in the young;
      however, case-fatality rates continue to be similar between races and are not
      changing over time. Medication use for treatment of stroke risk factors
      significantly increased in the general population between study periods.
      CONCLUSIONS: Despite advances in stroke prevention treatments during the 1990s,
      the incidence of hospitalized stroke did not decrease within our population. Case
      fatality also did not change between study periods. Excess stroke mortality rates
      seen in blacks nationally are likely the result of excess stroke incidence and
      not case-fatality, and the racial disparity in stroke incidence did not change
      over time.

PMID- 16946148
TI  - Age-related changes in carotid artery flow and pressure pulses: possible
      implications for cerebral microvascular disease.
AB  - BACKGROUND AND PURPOSE: We sought to establish the relation between the pulsatile
      components of pressure and flow waveforms in the carotid artery and their change
      with age. METHODS: Distention (pressure) and axial flow velocity waveforms were
      recorded noninvasively and simultaneously from the common carotid artery of 56
      healthy subjects aged 20 to 72 years. RESULTS: There was a close relation between
      the time intervals of pressure and flow waves: from foot to first shoulder or
      peak, to second shoulder or peak, and to incisura (r=0.97, P<0.0001 for each),
      which approximated the line of identity. The peak and nadir of flow velocity
      decreased with age, but late systolic flow augmentation increased substantially
      (1.6 times in the older group); this can be attributed to earlier wave reflection
      from the lower body. Pressure augmentation index (PAI) and flow augmentation
      index (FAI) increased similarly with age (PAI (%) = 0.84 x age - 26.6; FAI (%) =
      0.75 x age + 11.9; both P<0.0001). CONCLUSIONS: Arterial stiffening with aging
      increases carotid flow augmentation and can explain the increasing flow
      fluctuations in cerebral blood vessels. Measurement of carotid FAI may provide a
      gauge for risk of cerebral microvascular damage, just as PAI provides a gauge for
      risk of left ventricular hypertrophy and failure.

PMID- 16946147
TI  - Plasma fibrinogen concentrations and risk of stroke and its subtypes among
      Japanese men and women.
AB  - BACKGROUND AND PURPOSE: We aimed to examine the impact of fibrinogen
      concentrations on the incidence of stroke. METHODS: We examined the association
      between fibrinogen and risk of total stroke and stroke subtypes in an 11-year
      prospective study of 4608 men and 7589 women aged 40 to 79 years with no history
      of stroke and/or coronary heart disease. The analysis was repeated, stratified by
      smoking status, to examine whether the association between fibrinogen and stroke
      was modified by smoking. RESULTS: There were 317 incident total strokes
      comprising 103 hemorrhagic strokes (70 intraparenchymal hemorrhages [22.1% of
      strokes], 33 subarachnoid hemorrhages [10.4%]), 206 ischemic strokes (65.0%), and
      8 strokes of undetermined type (2.5%). The multivariable hazard ratio (95% CI)
      for the highest versus lowest fibrinogen quartiles after adjustment for age, sex,
      area, and known cardiovascular risk factors was 2.5 (1.3 to 5.0), P<0.01, for
      hemorrhagic stroke and 3.2 (1.4 to 7.4), P<0.01, for intraparenchymal hemorrhage.
      There was no positive association of fibrinogen with risk of ischemic stroke or
      subarachnoid hemorrhage. Among never-smokers, the multivariable hazard ratio (95%
      CI) for the highest versus lowest fibrinogen quartiles was 3.5 (1.3 to 9.3),
      P=0.01, for hemorrhagic stroke and 4.4 (1.3 to 15.2), P=0.02, for
      intraparenchymal hemorrhage. CONCLUSIONS: High plasma fibrinogen concentration
      can be a predictor for risk of intraparenchymal hemorrhage.

PMID- 16946149
TI  - Clarification.

PMID- 16946150
TI  - On the analysis and interpretation of outcome measures in stroke clinical trials:
      lessons from the SAINT I study of NXY-059 for acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: A variety of primary end points have been used in acute
      stroke trials. We focus on the modified Rankin Scale, a reliable and valid
      ordinal outcome measure that assesses disability on a 7-point scale. METHODS: We
      provide an abbreviated discussion of analytical methods for ordinal scales, and
      related effect size measures; we illustrate these methods and their
      interpretation with outcome data from the SAINT I study of NXY-059 in acute
      ischemic stroke. RESULTS: The nonparametric Mann-Whitney statistic provides a
      straightforward method for analysis of the modified Rankin Scale, and
      incorporates associated measures of effect size. These measures are directly
      related to the concepts of Number Needed to Treat and Number Needed to Harm.
      CONCLUSIONS: Our re-examination of the outcome data from the SAINT I study
      provides little evidence for the purported efficacy of NXY-059. More broadly,
      analysis and interpretation of ordinal outcome scales based on ascribed numerical
      values to the steps of the scale should be done cautiously. Statistical treatment
      of multiple primary outcome measures in acute stroke clinical trials should be
      established before analysis. Lastly, conflating statistical and clinical
      significance should be avoided.

PMID- 16946151
TI  - Increased balloon-induced inflammation, proliferation, and neointima formation in
      apolipoprotein E (ApoE) knockout mice.
AB  - BACKGROUND AND PURPOSE: The pathophysiology of vascular lesions after balloon
      angioplasty remains poorly understood. A major limitation of most experimental
      studies in this regard is that injury was assessed in healthy arteries. Our aim
      was to study the effects of hypercholesterolemia in a mouse vascular injury model
      that mimics human balloon angioplasty. METHODS: Carotid balloon distension was
      performed in wild-type (WT) mice on a normal diet (ND), in apolipoprotein E
      deficient (ApoE-/-) mice on ND and in ApoE-/- mice fed a high cholesterol diet
      (CD). RESULTS: Medial cell death (TUNEL) was elevated in all mice at 1 hour and 1
      day after angioplasty without differences between the groups. We found enhanced
      intimal inflammation (%CD45-positive cells) and vascular cell adhesion molecule-1
      expression at 7 days (P < 0.05; n > or = 4) as well as increased proliferation
      rates (BrdU-index) in ApoE-/- CD at 7 and 28 days postinjury (P < 0.05; n > or =
      5). Four weeks after injury, these events led to enhanced neointima in ApoE-/- CD
      compared with WT ND mice (intima/media, P < 0.001; n > or = 8). The amount of
      lesion formation paralleled the incremental increase in total plasma cholesterol
      in WT ND, ApoE-/- ND and ApoE-/- CD (P < 0.01). CONCLUSIONS: Carotid balloon
      distension injury in ApoE-/- mice on CD induced enhanced inflammation and
      proliferation leading to increased neointima. Further applications of this
      microballoon catheter in genetically modified mice will provide opportunities to
      elucidate molecular mechanisms of vascular lesion formation in a model that
      reflects clinical balloon angioplasty. This know-how may pave the way to catheter
      based interventions of human microvessels in the peripheral or cerebral
      circulation.

PMID- 16946152
TI  - Transesophageal echocardiography is superior to transthoracic echocardiography in
      management of patients of any age with transient ischemic attack or stroke.
AB  - BACKGROUND AND PURPOSE: The merits of transthoracic echocardiography (TTE) and
      transesophageal echocardiography (TEE) in the management of transient ischemic
      attack (TIA) and stroke patients remains matter of debate. METHODS: Two hundred
      and thirty-one consecutive patients with a recent TIA or stroke for which no
      definite cause and indication for anticoagulation was assessed after standardized
      work-up underwent TTE and TEE. Echocardiographic findings were categorized into
      minor and major risk factors. RESULTS: A potential cardiac source of embolism was
      detected in 55% (127/ 231) of the patients by echocardiography, in 39% (90/231)
      only identified on TEE. Major risk factors, with an absolute indication for oral
      anticoagulation, were detected in 20% (46/231) of the patients, in 16% (38/231)
      of all patients identified on TEE only. A thrombus in the left atrial appendage
      was the most common major risk factor (38 patients, 16%). The presence of major
      risk factors was independent of age (chi2=1.48; P=0.224). The difference in
      proportions of cardiac sources detected in favor of TEE was highly significant in
      both patients < or = 45 years of age (10/39, P=0.002) and in those > 45 years of
      age (80/192; P<0.004). CONCLUSIONS: TEE proved superior to TTE for identification
      of a cardiac embolic source in patients with TIA or stroke without pre-existent
      indication or contraindication for anticoagulation. In patients with normal TTE,
      a cardiac source of embolism was detected by TEE in approximately 40% of
      patients, independent of age. More than 1 of 8 patients of any age with normal
      TTE revealed a major cardiac risk factor on TEE, in whom anticoagulation is
      warranted.

PMID- 16946153
TI  - Discontinuation of statin treatment in stroke patients.
AB  - BACKGROUND AND PURPOSE: Statins reduce the risk for myocardial infarctions and
      stroke which may in part depend on cholesterol-independent (pleiotropic)
      vasoprotective effects. Here, we review evidence to suggest that the abrupt
      discontinuation of statin medication exerts negative vascular effects in patients
      with acute vascular events. SUMMARY OF REVIEW: It is increasingly recognized that
      statins (HMG-CoA reductase inhibitors) exert rapid cholesterol-independent
      effects. Cessation of statin treatment confers overshoot activation of
      heterotrimeric G-proteins Rho and Rac causing production of reactive oxygen
      species and suppression of NO bioavailability. In humans, discontinuation of
      statin therapy leads to a proinflammatory, prothrombotic state with impaired
      endothelium function. In patients with acute coronary syndromes, abrupt
      discontinuation of statin therapy significantly increases morbidity and
      mortality, whereas in stable vascular patients discontinuation may be safe.
      Recent prospective data indicated that the cessation of statin medication in
      acute ischemic stroke patients confers a significantly higher likelihood of early
      neurological deterioration and poor outcome. CONCLUSIONS: We propose that in all
      acute ischemic stroke patients chronically treated with statins before the event,
      treatment should be continued and the patient should receive medication at the
      day of the stroke.

PMID- 16946154
TI  - Should spectrophotometry be used to identify xanthochromia in the cerebrospinal
      fluid of alert patients suspected of having subarachnoid hemorrhage?
AB  - BACKGROUND AND PURPOSE: The absence of xanthochromia in the cerebrospinal fluid
      (CSF) is often used to exclude subarachnoid hemorrhage (SAH). Authorities
      advocate spectrophotometry to measure xanthochromia, but most North American
      hospitals use visual inspection. We studied the diagnostic accuracy of
      spectrophotometry for SAH, and its potential impact on current practice. METHODS:
      This was a prospective cohort study comparing the diagnostic accuracy of tests.
      The study was set in 3 university-affiliated tertiary care emergency departments.
      We enrolled consecutive neurologically intact adults with nontraumatic headache
      undergoing lumbar puncture (LP) to rule out SAH. CSF was centrifuged, frozen and
      analyzed later in batch. SAH was defined by (1) subarachnoid blood on CT, (2)
      >5x10(6) red blood cells/L in the final CSF tube and positive angiography, or (3)
      visible xanthochromia in CSF and positive angiography. All subjects lacking a
      normal CT and LP were telephoned at 30 days. RESULTS: We enrolled 220 patients
      (mean age 42+/-16 years; CT rate 87.7%; angiography rate 5.9%). Two SAHs were
      identified: 1 with red blood cells without xanthochromia in the CSF and 1 with
      visibly xanthochromic CSF. The specificity of xanthochromia was 97% (95% CI: 92%
      to 99%) for visual inspection, but as low as 29% (95% CI: 23% to 35%) for 2 of
      the spectrophotometric definitions. Introducing spectrophotometry could lead to
      angiography in as many as 11% to 71% of patients undergoing LP. CONCLUSIONS:
      Spectrophotometric definitions of xanthochromia have only moderate to low
      specificity for SAH. Using spectrophotometry could increase angiography rates,
      thereby identifying more incidental aneurysms, increasing patient anxiety and
      exposing patients to unnecessary surgical or investigational complications
      without benefit.

PMID- 16946155
TI  - Cerebral microbleeds are associated with lacunar stroke defined clinically and
      radiologically, independently of white matter lesions.
AB  - BACKGROUND AND PURPOSE: Associations among microbleeds, white matter lesions
      (WMLs), and small deep infarcts on imaging have been reported. Because many of
      these imaging infarcts were asymptomatic, the relationship of microbleeds to
      clinical lacunar stroke is unclear. An association between microbleeds and
      clinically defined lacunar stroke might suggest a common causal microangiopathy.
      METHODS: Patients with lacunar, partial anterior circulation or posterior
      circulation stroke syndromes and older healthy subjects underwent MRI.
      Microhemorrhages, infarcts, hemorrhages, and WMLs were coded blind to clinical
      details. A final clinicoradiologic stroke subtype diagnosis was assigned.
      RESULTS: Among 308 subjects (67 older healthy and 241 with stroke), 54 patients
      had microbleeds (17%). Microbleeds were twice as frequent in lacunar than
      cortical strokes (26% versus 13%, P=0.03) or healthy older subjects (9%) and
      associated with increasing WML scores (P<0.0001). Lacunar and cortical stroke
      subtypes and healthy older subjects had similar WML scores. CONCLUSIONS:
      Microbleeds are associated with lacunar stroke defined clinicoradiologically more
      than other stroke subtypes but not simply by association with WMLs. This suggests
      that microbleeds and lacunar stroke have a similar microvascular abnormality.

PMID- 16946156
TI  - NXY-059: a hopeful sign in the treatment of stroke.

PMID- 16946158
TI  - Impact of stroke on health-related quality of life in the noninstitutionalized
      population in the United States.
AB  - BACKGROUND AND PURPOSE: Stroke is a major cause of long-term disability in the
      United States. This study examined the national impact of stroke on health
      related quality of life (HRQoL) and disparities in HRQoL across different
      demographic groups. METHODS: Combined 2000 and 2002 Medical Expenditure Panel
      Survey data were used, which include quality-of-life measures based on the short
      form generic measures (SF-12) and the EuroQol Group measures (EQ-5D index and EQ
      VAS) for 39,680 adults aged >18 years. Stratified analysis and ordinary least
      square regressions were used to compare HRQoL scores between stroke and nonstroke
      populations. RESULTS: The study included 1040 noninstitutionalized stroke
      survivors. After adjustment for sociodemographics, risk factors, and
      comorbidities, stroke survivors had statistically significantly lower mean scores
      for mental health (-4.1%), physical health (-7.9%), health utility (-6.9%), and
      self-rated health (-7.2%) (all P<0.01). In general, stroke did not affect
      differences in HRQoL among age or gender groups. However, racial and ethnic
      disparities in HRQoL were greater among stroke survivors than nonstroke
      individuals, particularly in health utility scores for black vs white
      participants (-0.06 in stroke survivors and -0.02 in the nonstroke population,
      P<0.01) and Hispanic versus non-Hispanic participants (-0.11 in stroke survivors
      and -0.01 in the nonstroke population). CONCLUSIONS: Stroke significantly impairs
      HRQoL in the United States. The findings suggest that racial and ethnic
      disparities in HRQoL among stroke survivors are more pronounced than in the
      nonstroke population. The burden of nonfatal stroke, especially among racial and
      ethnic minorities, should be recognized more widely.

PMID- 16946157
TI  - Population-based study of determinants of initial secondary care costs of acute
      stroke in the United Kingdom.
AB  - BACKGROUND AND PURPOSE: To determine the cost-effectiveness of specific
      interventions to prevent or treat acute stroke, it is necessary to know the costs
      of stroke according to patient characteristics and stroke subtype and etiology.
      However, very few such data are available and none from population-based studies.
      We determined the predictors of resource use and acute care costs of stroke using
      data from a population-based study. METHODS: Data were obtained from the Oxford
      Vascular study, a population-based cohort of all individuals in nine general
      practices in Oxfordshire, UK, which identified 346 patients with a first or
      recurrent stroke during April 1, 2002, to March 31, 2004. Univariate and
      multivariate analyses were performed to identify the main predictors of resource
      use and costs. RESULTS: Acute care costs ranged from 326 pounds sterling (lower
      decile) to 19,901 pounds sterling (upper decile). There were multiple important
      univariate interrelations of patient characteristics, stroke subtype, and stroke
      etiology with hospital admission, length of stay, and 30-day case-fatality. For
      example, patients with primary intracerebral hemorrhage were more likely to be
      admitted than patients with partial anterior circulation ischemic stroke and less
      likely to survive without disability, but length of stay was reduced as a result
      of high early case-fatality such that cost was substantially less. However, the
      majority of univariate predictors of resource use, cost, and outcome were
      confounded by initial stroke severity as measured by the National Institutes of
      Health Stroke Scale score, which accounted for approximately half of the
      predicted variance in cost. Cost increased approximately linearly up to an
      National Institutes of Health Stroke Scale score of 18 and then fell steeply at
      higher scores as a result of rising early case-fatality. CONCLUSIONS: Several
      patient and event-related characteristics explained the wide range of initial
      secondary care costs of acute stroke, but stroke severity was by far the most
      important independent predictor.

PMID- 16946159
TI  - Stroke propagates bacterial aspiration to pneumonia in a model of cerebral
      ischemia.
AB  - BACKGROUND AND PURPOSE: Bacterial pneumonia is the most common cause of death in
      patients sustaining acute stroke and is believed to result from an increased
      aspiration. Recently, stroke-induced immunodeficiency was described in a mouse
      model of cerebral ischemia, which is primarily caused by overactivation of
      sympathetic nervous system. We tested if stroke-induced immunodeficiency
      increases the risk of pneumonia after aspiration in a newly developed model of
      poststroke pneumonia. METHODS: Experimental stroke in mice was induced by
      occlusion of the middle cerebral artery (MCAO) for 60 minutes. Aspiration
      pneumonia was induced by intranasal application of 20 microL of a defined
      suspension of Streptococcus pneumoniae in phosphate-buffered saline 4 or 14 days
      after MCAO. Treatment comprised moxifloxacin (100 mg/kg body weight, six times
      every 2 hours after operation) or propranolol (30 mg/kg body weight, immediately
      before as well as 4 and 8 hours after MCAO). Readout was lung histology and
      bacterial counts in lung and blood. RESULTS: Nasal inoculation of only 200 colony
      forming units of S. pneumoniae caused severe pneumonia and bacteremia after
      experimental stroke, whereas 200,000 colony-forming units are needed to induce
      comparable disease in sham animals. Aspiration pneumonia in stroke animals
      outlasted acute stroke state but was preventable by beta-adrenoreceptor blockade.
      CONCLUSIONS: Experimental stroke propagates bacterial aspiration from harmless
      intranasal colonization to harmful pneumonia. Prevention of infections by beta
      adrenoreceptor blockade suggests that immunodepression by sympathetic
      hyperactivity is essential for progression of bacterial aspiration to pneumonia.

PMID- 16946160
TI  - Adeno-associated viral-vector-mediated hypoxia-inducible vascular endothelial
      growth factor gene expression attenuates ischemic brain injury after focal
      cerebral ischemia in mice.
AB  - BACKGROUND AND PURPOSE: Exogenous delivery of vascular endothelial growth factor
      gene (VEGF) may provide a useful approach to the treatment of brain ischemia. We
      investigated the use of a hypoxia-responsive element to control VEGF expression
      given for neuroprotection. METHODS: Three groups (n=36) of mice received AAVH9
      VEGF, AAVH9-lacZ, or saline injection. Five days after gene transfer, the mice
      underwent 45 minutes of transient middle cerebral artery occlusion (tMCAO)
      followed by 1 to 7 days of reperfusion. Infarct volume was determined using
      cresyl violet staining; neuronal injury was examined using TUNEL, cleaved caspase
      3, and fluoro-Jade B staining. RESULTS: Hypoxia-inducible factor-1 (HIF-1) was
      overexpressed after tMCAO in the ischemic hemisphere in the brain. Expression of
      lacZ, mediated by AAV-lacZ, was seen before and after tMCAO; however, AAVH9-lacZ
      mediated lacZ expression was detected only after tMCAO. Infarct volume was
      smaller in the AAVH9-VEGF-transduced group compared with AAVH9-lacZ and saline
      groups (55% reduction, P<0.05) with reduced TUNEL (29+/-5% and 30+/-7% versus
      12+/-3%, P<0.05), cleaved caspase-3 (20+/-3% and 21+/-5% versus 13+/-4%, P<0.05)
      and fluoro-Jade B (23+/-3% and 24+/-5% versus 12+/-5%, P<0.05) -positive neurons,
      respectively. CONCLUSIONS: Exogenous expression of VEGF through AAVH9-VEGF gene
      transfer 5 days before the onset of ischemia provides neuroprotection. Hypoxia
      responsive element is a viable strategy of restricting VEGF expression to areas
      of ischemia to minimize adverse effects of therapy on adjacent normal parenchyma.

PMID- 16946162
TI  - Effects of cerebral ischemia on evoked cerebral blood oxygenation responses and
      BOLD contrast functional MRI in stroke patients.
AB  - BACKGROUND AND PURPOSE: To evaluate the mechanisms of failure of blood
      oxygenation level-dependent (BOLD) imaging in stroke, we compared the evoked
      cerebral blood oxygenation (CBO) responses and activation volumes (AVs) of BOLD
      functional MRI (fMRI) in chronic stroke patients with moderate and severe
      cerebral ischemia. METHODS: We measured the evoked CBO responses in the primary
      sensorimotor cortex (PSMC) by means of near-infrared spectroscopy during
      contralateral motor tasks. We compared the AV of BOLD-functional MRI in the PSMC
      on the nonlesion and lesion sides. Single-photon emission computed tomography was
      used to classify ischemic status as moderate (slight reduction of regional
      cerebral blood flow and cerebrovascular reserve capacity [CVRC]) or severe
      (marked reduction of regional cerebral blood flow and CVRC; ie, misery
      perfusion). RESULTS: In age-matched controls, deoxyhemoglobin concentration
      decreased with concomitant increases in oxyhemoglobin and total hemoglobin
      concentrations during activation. The PSMC on the nonlesion side exhibited a
      normal CBO response pattern. On the lesion side, moderate cerebral ischemia did
      not affect the CBO response pattern, but severe cerebral ischemia caused an
      increase of deoxyhemoglobin during the task, associated with increases of
      oxyhemoglobin and total hemoglobin. Moderate cerebral ischemia induced only a
      slight reduction of the AV on the lesion side; however, severe cerebral ischemia
      markedly reduced the AV on the lesion side. The BOLD signal did not change in
      some areas of the PSMC on the lesion side in severe cerebral ischemia, whereas it
      tended to decrease in other areas during the tasks. CONCLUSIONS: Misery perfusion
      caused a marked reduction of the AV on BOLD imaging, associated with an increase
      of deoxyhemoglobin concentration during activation. BOLD-fMRI investigations of
      stroke patients should be performed while giving consideration to baseline
      circulatory status. Functional near-infrared spectroscopy could be an alternative
      means to assess the CVRC.

PMID- 16946161
TI  - Stroke among patients with dizziness, vertigo, and imbalance in the emergency
      department: a population-based study.
AB  - BACKGROUND AND PURPOSE: Dizziness, vertigo, and imbalance are common presenting
      symptoms in the emergency department. Stroke is a leading concern even when these
      symptoms occur in isolation. The objective of the present study was to determine
      the "real-world" proportion of stroke among patients presenting to the emergency
      department with these dizziness symptoms (DS). METHODS: From a population-based
      study, patients >44 years of age presenting with DS to the emergency department,
      or directly admitted to the hospital, were identified. Demographics, the
      frequency of new cerebrovascular events, and the frequency of isolated DS (ie DS
      with no other stroke screening term or accompanying neurologic signs or symptoms)
      were assessed. Multivariable logistic regression was used to evaluate the
      association of age, gender, ethnicity, and isolated DS with stroke/transient
      ischemic attack (TIA). The association of the presenting symptoms with stroke/TIA
      was also assessed. RESULTS: Stroke/TIA was diagnosed in 3.2% (53 of 1666) of all
      patients with DS. Only 0.7% (9 of 1297) of those with isolated DS had a
      stroke/TIA. Patients with stroke/TIA were slightly older than those without
      stroke/TIA (69.3+/-11.7 vs 65.3+/-12.9, P=0.02). Male gender was associated with
      stroke/TIA, whereas isolated DS was negatively associated with stroke/TIA.
      Patients with imbalance (dizziness as referent) were more likely to have
      stroke/TIA. CONCLUSIONS: The proportion of cerebrovascular events in patients
      presenting with dizziness, vertigo, or imbalance is very low. Isolated dizziness,
      vertigo, or imbalance strongly predicts a noncerebrovascular cause. The symptom
      of imbalance is a predictor of stroke/TIA.

PMID- 16946163
TI  - Safety of cerebral digital subtraction angiography in children: complication rate
      analysis in 241 consecutive diagnostic angiograms.
AB  - BACKGROUND AND PURPOSE: Catheter-based cerebral angiography remains an important
      diagnostic tool in the pediatric population, particularly considering the
      currently growing interest in diagnosing and treating cerebrovascular disorders
      in children. There are no recent estimates of the complication rate associated
      with modern diagnostic digital subtraction angiography (DSA) in the pediatric
      population. The purpose of this study was to estimate the rate of complications
      occurring during cerebral angiography in children. METHODS: Data from 241
      consecutive pediatric cerebral angiograms performed at a single institution were
      entered into an institutional review board-approved database. Information on
      patient demographics, DSA indication, neurovascular diagnosis, and intra
      procedural and postprocedural complications was collected. RESULTS: Our
      population included 115 boys and 90 girls, with age ranging from 1 week to 18
      years (mean+/-SD, 12+/-5 years). All angiograms were technically successful. No
      intraprocedural complication was noted; in particular, there was no occurrence of
      iatrogenic vessel injury (dissection) and no transient or permanent neurological
      deficit secondary to a thromboembolic event. One child with a complex dural
      arteriovenous fistula experienced a fatal intracranial rehemorrhage secondary to
      a posterior fossa varix rupture 3 hours after completion of an uneventful
      diagnostic angiogram. The rates of intraprocedural and postprocedural
      complications were therefore 0.0% (95% CI, 0.0% to 1.4%) and 0.4% (95% CI, 0.012%
      to 2.29%), respectively. CONCLUSIONS: The rate of immediate complications
      occurring during diagnostic cerebral angiography in children is very low. No
      intraprocedural complication was documented in the reported series. DSA performed
      by experienced angiographers is a safe procedure that can provide critical
      diagnostic information.

PMID- 16946165
TI  - Long-term cognitive transitions, rates of cognitive change, and predictors of
      incident dementia in a population-based first-ever stroke cohort.
AB  - BACKGROUND AND PURPOSE: There are few data on long-term cognitive outcomes after
      first-ever stroke. We aimed to study long-term cognitive transitions, rates of
      cognitive change, and factors associated with incident dementia and cognitive
      impairment-no dementia (CIND) 2 years after first-ever stroke. METHODS: A
      population-based cohort of incident first-ever stroke cases (n=99; mean age, 69.9
      years) and an age- and sex-matched comparison group (nonstrokes, n=99) were
      followed up for 2 years by 3 serial examinations. Rates of cognitive change were
      compared by repeated-measures analyses. Factors associated with incident dementia
      and CIND at 2 years were determined by multinomial logistic regression. RESULTS:
      Significant stroke x time interactions were present for all cognitive domains,
      with stroke cases showing a greater rate of decline compared with nonstrokes.
      Stroke recurrence during follow-up was responsible for significantly greater
      global decline. Strokes with recurrence (P=0.02), age (P=0.004), and baseline
      cognitive impairment (P<0.001) were independently associated with incident
      dementia at 2 years. Strokes without recurrence (P=0.008), age (P=0.001), and
      baseline cognitive impairment (P<0.001) were independently associated with CIND
      at 2 years. CONCLUSIONS: Recurrent stroke contributes importantly to global
      cognitive decline after a first-ever stroke. Secondary stroke prevention will be
      important in ameliorating dementia related to stroke. Mechanisms underlying the
      progression of early cognitive impairment to dementia in stroke patients need
      further investigation.

PMID- 16946164
TI  - Long-term changes of functional MRI-based brain function, behavioral status, and
      histopathology after transient focal cerebral ischemia in rats.
AB  - BACKGROUND AND PURPOSE: The relation between recovery of brain function and
      neurological status after clinical and experimental cerebral ischemia is
      incompletely characterized. We assessed the evolution of ischemic injury,
      behavioral status, and brain activity at acute to chronic periods after transient
      middle cerebral artery occlusion (tMCAO) in rats. METHODS: Male Sprague-Dawley
      rats were subjected to 20-minute tMCAO (n=10) or sham operation (n=10).
      Sensorimotor behavioral testing and multimodal (diffusion, perfusion, T2, and
      functional) MRI, as well as postmortem hematoxylin-eosin staining, were performed
      before and up to 21 days after tMCAO. MRI and histological parameters were
      evaluated in 5 regions of interest within the sensorimotor network. Diffusion,
      perfusion, and T2 lesion volumes were calculated according to previously
      established viability thresholds. RESULTS: Diffusion and perfusion lesions were
      present during occlusion but disappeared completely and permanently within 30
      minutes after reperfusion, with no T2 lesions seen. Functional MRI and behavioral
      deficits did not normalize until 1 and 21 days after tMCAO, respectively.
      Histology demonstrated selective neuronal cell death at 7 and 21 days after
      reperfusion. CONCLUSIONS: Twenty-minute tMCAO produced distinct changes on
      multimodal MRI, histology, and behavioral parameters acutely and chronically.
      Normal findings on MRI after transient ischemia may not indicate normal tissue
      status, as behavioral and histological anomalies remain. Behavioral dysfunction
      persisting long after the recovery of MRI parameters may relate to the subtle
      neuronal damage seen on histology. Together, these results may help explain
      unremitting neurological deficits in stroke or transient ischemic attack patients
      with normal MRI findings.

PMID- 16946166
TI  - Feasibility of acute clinical trials during aerial interhospital transfer.
AB  - BACKGROUND AND PURPOSE: In rural America, patients are often first seen at a
      small community hospital and then transferred to a tertiary care center by
      helicopter for further care. If acute clinical research were feasible during the
      aerial interhospital transport, more patients might be enrolled in trials at a
      critical earlier stage. METHODS: Prospective data were collected for all aerial
      transfers of a university-based helicopter service from April 2005 to January
      2006. Flight nurses were educated about stroke research and offered certification
      and participation. Data collected included patient characteristics and the
      availability of relatives to provide surrogate consent. RESULTS: All 12 flight
      nurses completed the institutional review board certification requirements and
      collected data on 215 transfers. Sixty-one patients had acute stroke or
      myocardial events (MIs). The median time from symptom onset to helicopter arrival
      at an outside hospital was 213 minutes (range, 90 to 2135) for ischemic stroke
      (n=12), 186 (45 to 1332) for intracranial hemorrhage (n=28), and 157 (47 to 1044)
      for MI (n=21). A relative was available in >74% of those transfers. A trial with
      a 4-hour window would permit enrollment of 67% of the ischemic strokes, 82% of
      intracranial hemorrhage cases, and 76% of MI patients. CONCLUSIONS: Clinical
      trials are feasible during aerial interhospital transport of patients. Flight
      nurses became successful investigators in clinical research and were exposed to
      potentially eligible patients with the ability to consent either directly or
      through surrogates. This approach could improve current clinical trial
      recruitment in rural areas, as well as permit testing of inflight ancillary
      interventions to improve outcome during patient transport.

PMID- 16946167
TI  - Conflict of interest, round 2.

PMID- 16946168
TI  - Keeping our eyes on STAR*D.

PMID- 16946169
TI  - A note on the partnership between psychiatry and primary care.

PMID- 16946170
TI  - Mood disorders and workplace performance: half a loaf.

PMID- 16946171
TI  - Central mechanisms for thyroid hormone regulation.

PMID- 16946172
TI  - Treatments for later-life depressive conditions: a meta-analytic comparison of
      pharmacotherapy and psychotherapy.
AB  - OBJECTIVE: To improve interventions for depressed older adults, data are needed
      on the comparative effects of pharmacotherapy versus psychotherapy. Given that
      most older adults with clinically significant depressive symptoms do not have
      major depression, data on treatments for minor depression and dysthymia are
      especially needed. METHOD: Meta-analysis was used to integrate the results of 89
      controlled studies of treatments focused on acute major depression (37 studies)
      and other depressive disorders (52 studies conducted with mixed diagnostic
      groups, including patients with major depression, minor depression, and
      dysthymia). A total of 5,328 older adults received pharmacotherapy or
      psychotherapy in these studies. RESULTS: Clinician-rated depression scores
      improved, on average, by 0.80 standard deviation (SD) units; self-rated
      depression scores improved by 0.76 SD units. Clinician-rated depression improved
      by 0.69 SD units in pharmacotherapeutic studies and by 1.09 SD units in
      psychotherapeutic studies. Self-rated depression improved by 0.62 SD units and
      0.83 SD units, respectively. An interesting finding was the stronger improvements
      in clinician-rated depression among control subjects participating in medication
      studies, compared to those in psychotherapeutic studies. CONCLUSIONS: Available
      treatments for depression work, with effect sizes that are moderate to large.
      Comparisons of psychotherapy and pharmacotherapy must be interpreted with
      caution, in part because medication studies are more likely to use a credible
      active placebo, which may lead to smaller adjusted effect sizes in medication
      studies. Given that psychotherapy and pharmacotherapy did not show strong
      differences in effect sizes, treatment choice should be based on other criteria,
      such as contraindications, treatment access, or patient preferences.

PMID- 16946173
TI  - SSRI-associated sexual dysfunction.

PMID- 16946174
TI  - Conversion disorder.

PMID- 16946175
TI  - Jacob A. Arlow (1912-2004).

PMID- 16946176
TI  - A comparison of lithium and T(3) augmentation following two failed medication
      treatments for depression: a STAR*D report.
AB  - OBJECTIVE: More than 40% of patients with major depressive disorder do not
      achieve remission even after two optimally delivered trials of antidepressant
      medications. This study compared the effectiveness of lithium versus
      triiodothyronine (T(3)) augmentation as a third-step treatment for patients with
      major depressive disorder. METHOD: A total of 142 adult outpatients with
      nonpsychotic major depressive disorder who had not achieved remission or who were
      intolerant to an initial prospective treatment with citalopram and a second
      switch or augmentation trial were randomly assigned to augmentation with lithium
      (up to 900 mg/day; N=69) or with T(3) (up to 50 mug/day; N=73) for up to 14
      weeks. The primary outcome measure was whether participants achieved remission,
      which was defined as a score < or =7 on the 17-item Hamilton Depression Rating
      Scale. RESULTS: After a mean of 9.6 weeks (SD=5.2) of treatment, remission rates
      were 15.9% with lithium augmentation and 24.7% with T(3) augmentation, although
      the difference between treatments was not statistically significant. Lithium was
      more frequently associated with side effects (p=0.045), and more participants in
      the lithium group left treatment because of side effects (23.2% versus 9.6%;
      p=0.027). CONCLUSIONS: Remission rates with lithium and T(3) augmentation for
      participants who experienced unsatisfactory results with two prior medication
      treatments were modest and did not differ significantly. The lower side effect
      burden and ease of use of T(3) augmentation suggest that it has slight advantages
      over lithium augmentation for depressed patients who have experienced several
      failed medication trials.

PMID- 16946177
TI  - Tranylcypromine versus venlafaxine plus mirtazapine following three failed
      antidepressant medication trials for depression: a STAR*D report.
AB  - OBJECTIVE: The purpose of this study was to compare the effectiveness and
      tolerability of tranylcypromine and combination treatment with extended-release
      venlafaxine and mirtazapine in patients with treatment-resistant major depression
      whose current depressive episode had not responded adequately to treatment in
      three prior prospective medication trials. METHOD: Adult outpatients with
      nonpsychotic major depressive disorder who had not achieved remission or had
      withdrawn from treatment because of intolerance in three previous prospective
      medication trials were randomly assigned to receive open-label treatment with
      either tranylcypromine (N=58) or extended-release venlafaxine plus mirtazapine
      (N=51). The primary outcome measure was whether patients achieved remission,
      which was defined as a score < or =7 at exit on the 17-item Hamilton Depression
      Rating Scale (HAM-D). The HAM-D was administered by telephone by raters to whom
      treatment was masked. RESULTS: Remission rates were not significantly different
      between the two treatment groups (6.9% for the tranylcypromine group and 13.7%
      for the venlafaxine plus mirtazapine group). The mean daily dose at exit for
      tranylcypromine was 36.9 mg (SD=18.5); for venlafaxine, 210.3 mg (SD=95.2); and
      for mirtazapine, 35.7 mg (SD=17.6). Tranylcypromine was associated with
      significantly less symptom reduction and greater attrition due to intolerance.
      CONCLUSIONS: Remission rates were modest for both the tranylcypromine group and
      the extended-release venlafaxine plus mirtazapine group, and the rates were not
      statistically different between groups. The lower side effect burden, lack of
      dietary restrictions, and ease of use of venlafaxine and mirtazapine suggest that
      this combination may be preferred over tranylcypromine for patients with highly
      treatment-resistant depression who have not benefited adequately from several
      prior treatments.

PMID- 16946178
TI  - Predictors of relapse in a prospective study of fluoxetine treatment of major
      depression.
AB  - OBJECTIVE: Loss of response to a previously effective antidepressant is a common
      clinical problem. Retrospective analyses have shown that the pattern of response
      during antidepressant treatment (late onset and persistent versus other patterns)
      can be used to predict relapse during continuation and maintenance treatment and
      possibly to identify placebo responses to treatment. This study was designed to
      test the predictive value of response pattern prospectively and to examine the
      data for other predictors of relapse. METHOD: Five hundred seventy persons with
      major depressive disorder were treated with fluoxetine for 12 weeks and their
      pattern of response was determined. Those who responded (N=292) underwent random
      assignment, under double-blind conditions, to continue taking fluoxetine or to
      switch to placebo for 52 weeks or until relapse. Survival analysis was used to
      examine the effect of covariates on relapse. RESULTS: Although fluoxetine was
      significantly more effective than placebo during maintenance treatment, this
      chronically ill group had a high rate of relapse. Contrary to previous findings,
      a pattern of acute response was not predictive of relapse. Chronicity, symptom
      severity, a neurovegetative symptom pattern, and female gender were all
      associated with a significantly greater risk of relapse, with no difference
      observed between fluoxetine and placebo. CONCLUSIONS: The pattern of response to
      acute treatment appears to be inconsistently predictive of relapse. There is a
      high rate of relapse with both active medication and placebo in patients with
      chronic depression. Illness characteristics predict loss of response both to
      fluoxetine and to placebo. No variable examined was predictive of differential
      relapse rates between fluoxetine and placebo.

PMID- 16946179
TI  - Familiality of postpartum depression in unipolar disorder: results of a family
      study.
AB  - OBJECTIVE: The authors previously reported strong evidence for familial
      aggregation of postpartum (puerperal) psychotic episodes in women with bipolar
      disorder. The authors here examine whether vulnerability to postpartum triggering
      of depressive episodes aggregates in families and assess how this aggregation
      varies with the definition of postpartum onset. METHOD: Postpartum depression
      occurrence was studied in the female members of 120 sibling pairs recruited at a
      site within an international multicenter study of sibling pairs with recurrent
      unipolar depression. Employing a range of definitions of postpartum onset, the
      authors examined concordance for postpartum episode status between sisters.
      RESULTS: Episodes of depression with onset within 4 weeks of delivery clustered
      in families, but there was no significant evidence of familial clustering of
      broadly defined postpartum depression (onset within 6 months). Among women with a
      family history of narrowly defined postpartum episodes, 42% experienced
      depression following their first delivery, whereas only 15% of women with no such
      family history experienced depression following first delivery. The evidence for
      familiality maximized with a postpartum onset definition of 6-8 weeks.
      CONCLUSIONS: These results implicate familial factors in susceptibility to the
      triggering of narrowly defined postpartum depressive episodes in women with
      recurrent major depression. They suggest that a postnatal onset definition of
      within 6-8 weeks of delivery may be optimal in studies of the triggering of
      depressive illness by childbirth.

PMID- 16946180
TI  - Familial aggregation of illness chronicity in recurrent, early-onset major
      depression pedigrees.
AB  - OBJECTIVE: The authors used a large sample collected for genetic studies to
      determine whether a chronic course of illness defines a familial clinical subtype
      in major depressive disorder. METHOD: A measure of lifetime chronicity of
      depressive symptoms (substantial mood symptoms most or all of the time) was
      tested for familial aggregation in 638 pedigrees from the Genetics of Recurrent
      Early-Onset Depression (GenRED) project. RESULTS: In subjects with chronic
      depression, the mean age at illness onset was lower and rates of attempted
      suicide, panic disorder, and substance abuse were higher than among those with
      nonchronic depression. Chronicity was assessed in 37.8% of affected first-degree
      relatives of probands with chronic depression and in 20.2% of relatives of
      probands with nonchronic depression. Analysis using the generalized estimating
      equation model yielded an odds ratio of 2.52 (SE=0.39, z=6.02, p<0.0001) for the
      likelihood of chronicity in a proband predicting chronicity in an affected
      relative. With stratification by proband age at illness onset, the odds ratio for
      chronicity in relatives by proband chronicity status was 6.17 (SE=2.09, z=5.35,
      p<0.0001) in families of probands whose illness onset was before age 13 and 1.92
      (SE=0.34, z=3.72, p<0.0001) in families of probands whose illness started at age
      13 or later. CONCLUSIONS: These findings suggest that chronicity of depressive
      symptoms is familial, especially in preadolescent-onset illness. Chronicity is
      also associated with other indicators of illness severity in recurrent, early
      onset major depression. Further study using chronicity as a subtype in the
      genetic analysis of depressive illness is warranted. Refinement of the definition
      of chronicity in depressive illness may increase the power of such studies.

PMID- 16946181
TI  - Prevalence and effects of mood disorders on work performance in a nationally
      representative sample of U.S. workers.
AB  - OBJECTIVE: Research on the workplace costs of mood disorders has focused largely
      on major depressive episodes. Bipolar disorder has been overlooked both because
      of the failure to distinguish between major depressive disorder and bipolar
      disorder and by the failure to evaluate the workplace costs of mania/hypomania.
      METHOD: The National Comorbidity Survey Replication assessed major depressive
      disorder and bipolar disorder with the World Health Organization (WHO) Composite
      International Diagnostic Interview (CIDI) and work impairment with the WHO Health
      and Work Performance Questionnaire. A regression analysis of major depressive
      disorder and bipolar disorder predicting Health and Work Performance
      Questionnaire scores among 3,378 workers was used to estimate the workplace costs
      of mood disorders. RESULTS: A total of 1.1% of the workers met CIDI criteria for
      12-month bipolar disorder (I or II), and 6.4% meet criteria for 12-month major
      depressive disorder. Bipolar disorder was associated with 65.5 and major
      depressive disorder with 27.2 lost workdays per ill worker per year. Subgroup
      analysis showed that the higher work loss associated with bipolar disorder than
      with major depressive disorder was due to more severe and persistent depressive
      episodes in those with bipolar disorder than in those with major depressive
      disorder rather than to stronger effects of mania/hypomania than depression.
      CONCLUSIONS: Employer interest in workplace costs of mood disorders should be
      broadened beyond major depressive disorder to include bipolar disorder.
      Effectiveness trials are needed to study the return on employer investment of
      coordinated programs for workplace screening and treatment of bipolar disorder
      and major depressive disorder.

PMID- 16946182
TI  - Job performance deficits due to depression.
AB  - OBJECTIVE: This study assessed the relationship between depression severity and
      job performance among employed primary care patients. METHOD: In a 2001-2004
      longitudinal observational study of depression's affect on work productivity, 286
      patients with DSM-IV major depressive disorder and/or dysthymia were compared to
      93 individuals with rheumatoid arthritis, a condition associated with work
      disability, and 193 depression-free healthy control subjects. Participants were
      employed at least 15 hours per week, did not plan to stop working, and had no
      major medical comorbidities. Measures at baseline, six, 12, and 18 months
      included the Work Limitations Questionnaire for work outcomes, and the Patient
      Health Questionnaire-9 for depression. RESULTS: At baseline and each follow-up,
      the depression group had significantly greater deficits in managing mental
      interpersonal, time, and output tasks, as measured by the Work Limitations
      Questionnaire: The rheumatoid arthritis group's deficits in managing physical job
      demands surpassed those of either the depression or comparison groups.
      Improvements in job performance were predicted by symptom severity. However, the
      job performance of even the "clinically improved" subset of depressed patients
      remained consistently worse than the control groups. CONCLUSIONS: Multiple
      dimensions of job performance are impaired by depression. This impact persisted
      after symptoms have improved. Efforts to reduce work-impairment secondary to
      depression are needed.

PMID- 16946183
TI  - Health disparities in care for depression possibly obscured by the clinical
      significance criterion.
AB  - BACKGROUND: In addition to symptoms, DSM-IV criteria for major depression require
      clinical significance, operationalized via reports of receipt of care or
      interference in functioning. The authors examined whether this confounding of
      symptoms with receipt of care and/or impairment affected racial differences in
      rates of major depression in the community. METHOD: Analysis of data from the
      1999 National Health Interview Survey for a nationally representative community
      sample of 30,801 adults administered the depression module of the Composite
      International Diagnostic Interview-Short Form. RESULTS: There were no differences
      between African American subjects and white/other subjects when diagnosis was
      based solely on symptoms. Symptomatic African American individuals were less
      likely to endorse either receipt of care or interference in functioning, so that
      the clinical significance criterion served to reduce their rates of DSM-IV
      diagnosis. CONCLUSIONS: The clinical significance criterion underestimates of the
      rate of depression for African American individuals relative to white/other
      subjects, which may in turn underestimate their need for services.

PMID- 16946184
TI  - Increased 5-HT(2A) receptor binding in euthymic, medication-free patients
      recovered from depression: a positron emission study with [(11)C]MDL 100,907.
AB  - OBJECTIVE: A previous positron emission tomography (PET) study reported increased
      serotonin 5-HT(2A) receptor binding in unmedicated depressed patients with high
      scores on the Dysfunctional Attitudes Scale. The purpose of the present study was
      to use the highly selective 5-HT(2A) receptor ligand [(11)C]MDL 100,907 in a PET
      imaging paradigm to assess 1) 5-HT(2A) receptor binding potential in euthymic
      subjects with a history of recurrent depression and 2) the relationship between
      receptor binding and scores on the Dysfunctional Attitudes Scale. METHOD:
      Cortical 5-HT(2A) receptor binding was measured in 20 unmedicated, fully
      recovered unipolar depressed patients and 20 age- and gender-matched comparison
      subjects. Regional estimates of binding potential were obtained using a
      reversible plasma input function compartmental model and the cerebellum as a
      reference region to estimate the free and non-specifically bound [(11)C]MDL
      100,907 in brain tissue. RESULTS: Relative to the comparison subjects, the
      recovered depressed patients demonstrated significantly higher 5-HT(2A) receptor
      binding potential in the frontal cortex (mean increase: 19%), parietal cortex
      (mean increase: 25%), and occipital cortex (mean increase: 19%). 5-HT(2A)
      receptor binding potential correlated negatively with age in both patients and
      comparison subjects and positively with the Dysfunctional Attitudes Scale in the
      recovered patients. CONCLUSIONS: These findings should be considered preliminary
      but suggest that recovered subjects with a history of recurrent major depression
      have elevated binding potential of cortical 5-HT(2A) receptors. The correlation
      of increased 5-HT(2A) receptor binding potential with increased scores on
      Dysfunctional Attitudes Scale supports earlier work suggesting that increased 5
      HT(2A) receptor availability characterizes a group of depressed patients with
      high levels of dysfunctional attitudes.

PMID- 16946185
TI  - Association of a triallelic serotonin transporter gene promoter region (5-HTTLPR)
      polymorphism with stressful life events and severity of depression.
AB  - OBJECTIVE: The lower expressing allele of the serotonin transporter gene 5'
      promoter region (5-HTTLPR) polymorphism is reported to be associated with
      susceptibility to depression and suicidality in response to stressful life
      events. The authors examined the relationship of a triallelic 5-HTTLPR
      polymorphism to stressful life events, severity of major depression, and
      suicidality. METHOD: Mood disorder subjects (N=191) and healthy volunteers
      (N=125), all Caucasian subjects of European origin, were genotyped for the
      triallelic 5-HTTLPR polymorphism (higher expressing allele: L(A); lower
      expressing alleles: L(G), S). All subjects underwent structured clinical
      interviews to determine DSM-IV diagnoses, ratings of psychopathology, stressful
      life events, developmental history, and suicidal behavior. CSF 5-HIAA was assayed
      in a subgroup of subjects. RESULTS: Lower expressing alleles independently
      predicted greater depression severity and predicted greater severity of major
      depression with moderate to severe life events compared with the higher
      expressing L(A) allele. No associations with suicidal behavior and CSF 5-HIAA
      were found. CONCLUSIONS: Lower expressing transporter alleles, directly and by
      increasing the impact of stressful life events on severity, explain 31% of the
      variance in major depression severity. The biological phenotype responsible for
      these effects remains to be elucidated.

PMID- 16946186
TI  - Elevated putamen D(2) receptor binding potential in major depression with motor
      retardation: an [11C]raclopride positron emission tomography study.
AB  - OBJECTIVE: Several antidepressants raise striatal dopamine, but the role of
      striatal dopamine during major depressive episodes is unclear. Striatal
      [(11)C]raclopride binding potential measured with positron emission tomography is
      an index of D(2) type receptors and is sensitive to extracellular dopamine levels
      (higher D(2) binding potential occurs when dopamine is lower). It was
      hypothesized that putamen D(2) binding potential would be higher during major
      depressive episodes featuring motor retardation. METHOD: Drug-free, nonsmoking
      subjects experiencing a major depressive episode (N=21) underwent
      [(11)C]raclopride PET imaging as did 21 healthy age-matched comparison subjects.
      Motor retardation was measured with the finger tapping test. RESULTS: The
      depressed subjects exhibiting motor retardation had significantly higher D(2)
      binding potential in both the left and right putamen than did healthy subjects,
      and putamen D(2) binding potential correlated significantly with motor speed in
      the depressed subjects. CONCLUSIONS: The results argue that extracellular
      dopamine is lower in subjects experiencing a major depressive episode that
      features motor retardation. This depression subtype should preferentially benefit
      from dopamine-increasing medications and should be targeted in future clinical
      trials of dopamine reuptake inhibitors.

PMID- 16946187
TI  - Increased brain activation during working memory in cognitively intact adults
      with the APOE epsilon4 allele.
AB  - OBJECTIVE: Altered patterns of brain activity during cognitive tasks have been
      demonstrated using functional magnetic resonance imaging (fMRI) in mild cognitive
      impairment and Alzheimer's disease. However, there have been few studies of
      adults at genetic risk for Alzheimer's disease prior to the onset of symptoms.
      The purpose of this study was to determine whether brain activation patterns
      associated with working memory differ as a function of apolipoprotein E (APOE)
      genotype in cognitively intact adults. METHOD: Participants were cognitively
      intact, healthy adults who completed genotyping, comprehensive neuropsychological
      testing, and structural and functional neuroimaging. Twenty-two participants had
      the APOE epsilon3/epsilon3 genotype, and 13 participants had the APOE
      epsilon3/epsilon4 genotype. The study employed an auditory verbal N-back task to
      probe working memory-related brain activity. RESULTS: The epsilon3/epsilon3 and
      epsilon3/epsilon4 groups did not differ in demographic characteristics, cognitive
      ability, mood, or in-scanner task performance. The epsilon3/epsilon4 group showed
      greater activity during working memory in the medial frontal and parietal regions
      bilaterally and in the right dorsolateral prefrontal cortex. There were no
      regions in which the epsilon3/epsilon3 group showed greater activation than the
      epsilon3/epsilon4 group. CONCLUSIONS: These results indicate that differences in
      brain activity are evident in cognitively intact individuals who are at risk for
      late-onset Alzheimer's disease by virtue of their APOE allele status. As
      neuroprotective interventions become available, early detection will increase in
      importance. The combination of genetic and functional neuroimaging strategies may
      prove useful for monitoring individuals at risk for Alzheimer's disease before
      the onset of cognitive symptoms.

PMID- 16946188
TI  - Prevention of late-life depression in primary care: do we know where to begin?
AB  - OBJECTIVE: This study attempted to compare two models for selective (people at
      elevated risk) and indicated (those with subsyndromal depressive symptoms)
      prevention and to determine the optimal strategy for prevention of late-life
      depression. METHOD: Onset was assessed at 3 years with the Geriatric Mental State
      AGECAT in a randomly selected cohort of 1,940 nondepressed and nondemented older
      people in Amsterdam. Risk factors that can easily be identified in primary care
      were used. RESULTS: The association of risk factors with depression incidence was
      expressed in absolute and relative risk estimates, number needed to treat, and
      population-attributable fractions. Prevention models were identified with
      classification and regression tree analyses. In the indicated prevention model,
      subsyndromal symptoms of depression were associated with a risk of almost 40% of
      developing depression and a number needed to treat of 5.8, accounting for 24.6%
      of new cases. Adding more risk factors raised the absolute risk to 49.3%, with a
      lower number needed to treat but also lower attributable fraction values. In the
      selective prevention model, spousal death showed the highest risk, becoming even
      higher if the subjects also had a chronic illness. Overall, the attributable
      fraction values in the indicated model were higher, identifying more people at
      risk. CONCLUSIONS: Consideration of the costs and benefits of both models in the
      context of the availability of evidence-based preventative interventions
      indicated that prevention aimed at elderly people with depressive symptoms is
      preferred. The focus on treatment should be readdressed; a new approach is
      needed, with a stronger emphasis on prevention.

PMID- 16946189
TI  - Association of a functional deficit of the BKCa channel, a synaptic regulator of
      neuronal excitability, with autism and mental retardation.
AB  - OBJECTIVE: Autism is a complex, largely genetic psychiatric disorder. In the
      majority of cases, the cause of autism is not known, but there is strong evidence
      for a genetic etiology. To identify candidate genes, the physical mapping of
      balanced chromosomal aberrations is a powerful strategy, since several genes have
      been characterized in numerous disorders. In this study, the authors analyzed a
      balanced reciprocal translocation arising de novo in a subject with autism and
      mental retardation. METHOD: The authors performed the physical mapping of the
      balanced 9q23/10q22 translocation by fluorescent in situ hybridization
      experiments using bacterial artificial chromosome clones covering the areas of
      interest. RESULTS: Findings revealed that the KCNMA1 gene, which encodes the
      alpha-subunit of the large conductance Ca(2+)-activated K(+) (BK(Ca)) channel, a
      synaptic regulator of neuronal excitability, is physically disrupted. Further
      molecular and functional analyses showed the haploinsufficiency of this gene as
      well as decreased activity of the coded BK(Ca )channel. This activity can be
      enhanced in vitro by addition of a BK(Ca )channel opener (BMS-204352). Further
      mutational analyses on 116 autistic subjects led to the identification of an
      amino acid substitution located in a highly conserved domain of the protein not
      found in comparison subjects. CONCLUSIONS: These results suggest a possible
      association between a functional defect of the BK(Ca) channel and autistic
      disorder and raise the hypothesis that deficits in synaptic transmission may
      contribute to the physiopathology of autism and mental deficiency.

PMID- 16946191
TI  - Further evidence for a developmental subtype of bipolar disorder defined by age
      at onset: results from the national epidemiologic survey on alcohol and related
      conditions.
AB  - OBJECTIVE: This study examines the relationship between age at onset of bipolar I
      disorder and illness characteristics among adults in a community sample. METHOD:
      The National Epidemiologic Survey on Alcohol and Related Conditions identified
      1,411 adults with bipolar disorder. For analyses, bipolar disorder subjects were
      divided into three age at onset groups: childhood (less than 13 years old,
      N=113), adolescence (13-18 years old, N=339), and adulthood (19 years or older,
      N=959). RESULTS: Nonremitting bipolar disorder was most prevalent among childhood
      onset subjects, and childhood-onset subjects were most likely to experience
      prolonged episodes. Antisocial personality disorder was most prevalent among
      childhood-onset subjects. Drug use disorders were more prevalent among childhood
      onset and adolescent-onset, as compared with adult-onset, subjects. Prevalence of
      mixed episodes or irritability did not differ significantly between groups.
      CONCLUSIONS: Findings corroborate clinical studies: illness characteristics among
      adults with childhood-onset bipolar disorder are similar to those described in
      children with bipolar disorder.

PMID- 16946190
TI  - Increased stress-induced inflammatory responses in male patients with major
      depression and increased early life stress.
AB  - OBJECTIVE: The authors sought to determine innate immune system activation
      following psychosocial stress in patients with major depression and increased
      early life stress. METHOD: Plasma interleukin (IL)-6, lymphocyte subsets, and DNA
      binding of nuclear factor (NF)-kB in peripheral blood mononuclear cells were
      compared in medically healthy male subjects with current major depression and
      increased early life stress (N=14) versus nondepressed male comparison subjects
      (N=14) before and after completion of the Trier Social Stress Test. RESULTS:
      Trier Social Stress Test-induced increases in IL-6 and NF-kappaB DNA-binding were
      greater in major depression patients with increased early life stress and
      independently correlated with depression severity, but not early life stress.
      Natural killer (NK) cell percentages also increased following stress. However,
      there were no differences between groups and no correlation between NK cell
      percentage and stress-induced NF-kappaB DNA-binding or IL-6. CONCLUSIONS: Male
      major depression patients with increased early life stress exhibit enhanced
      inflammatory responsiveness to psychosocial stress, providing preliminary
      indication of a link between major depression, early life stress and adverse
      health outcomes in diseases associated with inflammation.

PMID- 16946192
TI  - Association of the dysbindin gene with bipolar affective disorder.
AB  - OBJECTIVE: In the study of bipolar affective disorder and schizophrenia, there is
      some evidence suggesting a phenotypic and genetic overlap between the two
      disorders. A possible link between bipolar affective disorder and schizophrenia
      remains arguable, however. The authors hypothesized that dysbindin, which is a
      probable susceptibility gene for schizophrenia, was associated with bipolar
      affective disorder and tested this hypothesis using a case-control design study.
      METHOD: Participants included 213 patients with bipolar I disorder and 197
      comparison subjects. In each subject, 10 polymorphisms in the dysbindin gene were
      genotyped and assessed. RESULTS: Two polymorphisms showed individual genotypic
      association with bipolar I disorder. Multiple marker haplotypes were more
      strongly associated, with the rarer of the two common haplotypes being
      overrepresented in the patients with bipolar affective disorder. A similar
      finding was reported in patients with schizophrenia in a previous study.
      CONCLUSIONS: Findings suggest that the human dysbindin gene may play a role in
      the susceptibility to bipolar affective disorder, which underscores a potentially
      important area of etiological overlap with schizophrenia. The existence of shared
      genetic risk factors will, in time, lead to changes in the current nosology of
      major psychoses.

PMID- 16946193
TI  - Sex differences in amphetamine-induced displacement of [(18)F]fallypride in
      striatal and extrastriatal regions: a PET study.
AB  - OBJECTIVE: The authors examined gender differences in d-amphetamine-induced
      displacements of [(18)F]fallypride in the striatal and extrastriatal brain
      regions and the correlations of these displacements with cognition and sensation
      seeking. METHOD: Six women and seven men underwent positron emission tomography
      (PET) with [(18)F]fallypride before and after an oral dose of d-amphetamine.
      Percent displacements were calculated using regions of interest and parametric
      images of dopamine 2 (D(2)) receptor binding potential. RESULTS: Parametric
      images of dopamine release suggest that the female subjects had greater dopamine
      release than the male subjects in the right globus pallidus and right inferior
      frontal gyrus. Gender differences were observed in correlations of changes in
      cognition and sensation seeking with regional dopamine release. CONCLUSION:
      Findings revealed a greater dopamine release in women as well as gender
      differences in the relationship between regional dopamine release and sensation
      seeking and cognition.

PMID- 16946194
TI  - Less mood switching with venlafaxine?

PMID- 16946195
TI  - Compulsions in depression: stalking by text message.

PMID- 16946196
TI  - Reduced hippocampal and amygdalar volume in dissociative identity disorder: not
      such clear evidence.

PMID- 16946197
TI  - Antidepressant-induced or clinician-induced suicidality in depression?

PMID- 16946198
TI  - Dissociative disorder underdiagnosed due to undescriptive criteria?

PMID- 16946199
TI  - Comparing antipsychotic efficacy.

PMID- 16946200
TI  - Using a medical model with psychotic patients.

PMID- 16946201
TI  - Pierre Janet and the concept of dissociation.

PMID- 16946203
TI  - Emerging infections in obstetric and gynecologic practice.

PMID- 16946204
TI  - Prevalence of methicillin-sensitive and methicillin-resistant Staphylococcus
      aureus in pregnant women.
AB  - OBJECTIVE: To estimate the extent of Staphylococcus aureus vaginal-rectal
      colonization among pregnant women as severe S aureus infections have emerged in
      pregnant and postpartum women and infants. METHODS: We conducted a prospective
      surveillance study for methicillin-sensitive S aureus and methicillin-resistant S
      aureus on all routine de-identified vaginal-rectal prenatal group B streptococcus
      (GBS) screening cultures submitted to the microbiology laboratory of a tertiary
      care facility from January to July 2005. Standard microbiologic techniques and
      molecular analyses were used to detect community-associated methicillin-resistant
      S aureus strains. As opposed to health care-associated methicillin-resistant S
      aureus isolates, community-associated methicillin-resistant S aureus isolates
      were defined as those possessing the type IV or type V staphylococcal chromosomal
      cassette mec element and usually lacking a multidrug-resistant phenotype.
      RESULTS: A total of 2,963 GBS screening cultures were analyzed, from which 743
      (25.1%, 95% confidence interval [CI] 23.5-26.7%) GBS isolates and 507 (17.1%, 95%
      CI 15.7-18.5%) S aureus isolates were identified. Group B streptococcus
      colonization was significantly associated with S aureus colonization (prevalence
      odds ratio 2.1, 95% CI 1.7-2.5, P < .001). Of the S aureus isolates, 14 (2.8%,
      95% CI 1.4-4.2%) were methicillin-resistant, and 13 of these were determined to
      be community-associated methicillin-resistant S aureus. CONCLUSION: The
      prevalence of S aureus colonization identified in GBS screening cultures from
      pregnant women was substantial and associated with GBS co-colonization. Although
      we do not advocate routine screening of pregnant women for methicillin-sensitive
      S aureus and methicillin-resistant S aureus colonization, we recommend continued
      monitoring of both methicillin-sensitive S aureus and methicillin-resistant S
      aureus infections in this population and their infants.

PMID- 16946205
TI  - Evaluation of polymerase chain reaction for group B streptococcus detection using
      an improved culture method.
AB  - OBJECTIVE: The administration of antibiotic prophylaxis to laboring women who
      harbor Group B streptococci (GBS) depends on identification of carriers. We
      sought to evaluate the diagnostic accuracy of real-time polymerase chain reaction
      (PCR) for detection of GBS using a more stringent culture method. METHODS: Two
      swabs were used simultaneously to obtain rectovaginal GBS samples from consenting
      women. One swab was analyzed using a stringent, validated culture technology,
      which included direct plating onto selective agar and inoculation of a selective
      broth. The other swab was used for a commercial real-time PCR assay, which uses
      amplification to detect the presence of the cfb gene sequence of GBS DNA. We
      calculated the assay accuracy using sensitivity and specificity. RESULTS: A total
      of 233 samples were available. Both the culture and PCR methods were positive for
      59 and negative for 157 patients. The culture method was positive and PCR was
      negative in 9 patients. The culture was negative and the PCR positive for 8
      patients. The sensitivity of the PCR assay was 86.8% and specificity was 95.2%.
      The positive predictive value was 88.1% and the negative predictive value was
      94.6%. CONCLUSION: Although a rapid PCR assay may be useful to determine GBS
      status in the urgent intrapartum setting, the false-negative rate of 13.2% for
      the real-time PCR assay prohibits its use for standard GBS screening in the
      office.

PMID- 16946206
TI  - 17alpha-hydroxyprogesterone caproate for the prevention of preterm delivery: A
      cost-effectiveness analysis.
AB  - OBJECTIVE: To evaluate whether the use of 17alpha-hydroxyprogesterone caproate
      for the prevention of recurrent preterm deliveries is cost-effective. METHODS:
      Using decision-analysis modeling, we compared the cost-effectiveness of using
      17alpha-hydroxyprogesterone caproate in four subgroups: 1) Prior preterm
      deliveries less than 32 weeks; 2) prior preterm deliveries 32-37 weeks; 3) prior
      term delivery; and 4) no prior delivery. Each subgroup was compared with a "no
      treatment" group. Costs included those for 17alpha-hydroxyprogesterone caproate,
      hospital admissions, and complications from preterm deliveries. The main outcome
      measures include cost per quality-adjusted life-year gained and the number of
      preterm deliveries prevented. Secondary outcomes include neonatal complications
      prevented. One-way and multiway sensitivity analyses were performed. RESULTS: The
      use of 17alpha-hydroxyprogesterone caproate for the prevention of preterm
      deliveries result in cost-savings in women with prior preterm deliveries less
      than 32 weeks and 32-37 weeks. The sensitivity analyses revealed the model to be
      robust over a wide range of values for evaluated variables. CONCLUSION: Within
      our baseline assumptions, 17alpha-hydroxyprogesterone caproate was associated
      with cost-savings when used for the prevention of preterm deliveries in women
      with prior preterm deliveries.

PMID- 16946207
TI  - Outcomes of pregnancy beyond 37 weeks of gestation.
AB  - OBJECTIVE: The aim of the study was to evaluate pregnancy outcomes by weeks of
      gestation. A second aim was to assess the outcomes in groups with spontaneous or
      induced labor. METHODS: This was a prospective cohort study of singleton
      pregnancies delivered after 37 weeks of pregnancy covering a well defined region
      in Norway from 1990 to 2001 (N = 27,514). Linear regression, chi 2 tests, and
      multivariable logistic regression analysis were used. RESULTS: Maternal
      complications varied with gestational age, and were lowest at 39 weeks and
      highest postterm (cesarean delivery 12.3-21.6%, operative vaginal delivery 10.7
      15.4%, maternal hemorrhage 9.7-14.6%). Poor neonatal outcome varied with
      gestational age only for spontaneous labors (Apgar at 5 minutes less than 7 1.0
      2.3%, pH less than 7.10 3.4-5.2%), whereas induction of labor was a risk factor
      for delivery complications (odds ratio 1.3-2.8), independent of gestational
      weeks. CONCLUSION: Poor pregnancy outcomes vary with gestational age. Postterm
      pregnancy and induced labor are prognostic factors for poor outcome.

PMID- 16946208
TI  - Growing teratoma syndrome after ovarian germ cell tumors.
AB  - OBJECTIVE: To analyze a series of occurrences of growing teratoma syndrome after
      ovarian germ cell tumors. METHODS: We analyzed a database containing 103 patients
      affected by pure or mixed ovarian immature teratoma. RESULTS: We report 12
      patients fulfilling growing teratoma syndrome criteria (incidence 12%). The
      median interval between the diagnosis of ovarian immature teratoma and growing
      teratoma syndrome was 9 months (range 4-55). Growing teratoma syndrome was
      revealed by radiological examinations in nine cases (75%). In all cases but one,
      growing teratoma syndrome occurred in the site involved by the primary tumor. The
      peritoneum was the first site involved (10 cases, 83%). A complete surgical
      resection of the growing teratoma syndrome was done in eight cases. The median
      follow-up was 144 months. Four patients presented a late growing teratoma
      syndrome recurrence after treatment (second event), more than 5 years after the
      initial diagnosis, and 14 years later for one patient. All patients but one (lost
      to follow-up) were still alive at the end of the study. CONCLUSION: The treatment
      of growing teratoma syndrome consists of the surgical resection of the tumor, as
      completely as possible. Because of the possibility of very late recurrence of
      growing teratoma syndrome, a prolonged follow-up of patients treated for ovarian
      immature teratoma is mandatory.

PMID- 16946209
TI  - Prophylactic bilateral salpingo-oophorectomy compared with surveillance in women
      with BRCA mutations.
AB  - OBJECTIVE: The objective of this study was to evaluate clinical factors
      associated with choosing prophylactic bilateral salpingo-oophorectomy (BSO) over
      surveillance in women with a BRCA1 or BRCA2 mutation. METHODS: Between 1996 and
      2005, 139 women who tested positive for a BRCA1 or BRCA2 mutation were
      identified. Thirty-three women were excluded due to a personal history of ovarian
      or fallopian tube cancer before genetic testing, resulting in 106 women for the
      final analysis. The characteristics of women who underwent prophylactic BSO were
      compared with those choosing surveillance. RESULTS: Sixty-five of the BRCA
      mutation carriers (61%) underwent prophylactic BSO. Median age at BSO was 45.6
      years. Median time from disclosure of genetic test results to surgery was 4.6
      months. Eighty-five percent of women who underwent prophylactic BSO were parous
      compared with 66% of women who chose surveillance (P = .03). A previous diagnosis
      of breast cancer was noted in 72% of women who underwent prophylactic BSO
      compared with 46% of women undergoing surveillance (P < .01). Fifty-two women
      (80%) had hysterectomy performed at the time of BSO. Two women had incidental
      ovarian cancer diagnosed at time of surgery. CONCLUSION: Age greater than 40
      years, parity, and a personal history of breast cancer were associated with
      choosing prophylactic BSO in our cohort. A short time interval was noted from the
      time of receiving positive genetic test results to undergoing prophylactic
      surgery.

PMID- 16946210
TI  - Patterns and progress in ovarian cancer over 14 years.
AB  - OBJECTIVE: To estimate the change in survival rates of women with ovarian cancer
      during the past 14 years. METHODS: Women diagnosed with epithelial, germ cell,
      sarcomas, and sex-cord stromal ovarian tumors were identified from the
      Surveillance Epidemiology and End Results Database. Demographic and
      clinicopathologic factors, and survival information were extracted and tested
      using chi 2 and Kaplan-Meier and Cox regression analyses. RESULTS: A total of
      30,246 women were diagnosed with ovarian cancer, including 26,753 non-clear cell
      epithelial, 1,411 clear cell, 818 sarcoma, 778 germ cell, and 486 sex-cord
      stromal tumors. The 5-year disease-specific survival rate across 1988-1992 and
      1993-1997 improved from 45.4% to 48.6% (P < .001). The corresponding estimates
      show increases for non-clear cell epithelial carcinoma from 42.5% to 45.8% (P <
      .001), and for sarcomas from 33.5% to 38.8% (P = .07). However, improvements were
      not observed in those with clear cell, 64.3% to 63.9% (P = .82), and sex-cord
      stromal, 89.7% to 85.7% (P = .18), tumors of the ovary. In multivariable
      analyses, younger age, early stage, favorable histologic cell types, low-grade
      tumors, standard surgery, and recent time interval from 1993-1997 were
      independent prognostic factors for improved survival. CONCLUSION: In this large
      population-based study, there has been some improvement in the overall survival
      of women with ovarian cancers during a 14-year period. However, new treatment
      strategies are warranted for those with epithelial cancer and sarcomas of the
      ovary, given their overall poor prognosis. These results from our updated
      analyses might help to counsel women diagnosed with ovarian cancers.

PMID- 16946211
TI  - Innervation of the pelvic floor muscles: a reappraisal for the levator ani nerve.
AB  - OBJECTIVE: We investigated the clinical anatomy of the levator ani nerve and its
      topographical relationship with the pudendal nerve. METHODS: Ten female pelves
      were dissected and a pudendal nerve blockade was simulated. The course of the
      levator ani nerve and pudendal nerve was described quantitatively. The anatomical
      data were verified using (immuno-)histochemically stained sections of human fetal
      pelves. RESULTS: The levator ani nerve approaches the pelvic-floor muscles on
      their visceral side. Near the ischial spine, the levator ani nerve and the
      pudendal nerve lie above and below the levator ani muscle, respectively, at a
      distance of approximately 6 mm from each other. The median distance between the
      levator ani nerve and the point of entry of the pudendal blockade needle into the
      levator ani muscle was only 5 mm. CONCLUSION: The levator ani nerve and the
      pudendal nerve are so close at the level of the ischial spine that a transvaginal
      "pudendal nerve blockade" would, in all probability, block both nerves
      simultaneously. The clinical anatomy of the levator ani nerve is such that it is
      prone to damage during complicated vaginal childbirth and surgical interventions.

PMID- 16946212
TI  - Cost-effectiveness of thromboprophylaxis with intermittent pneumatic compression
      at cesarean delivery.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of thromboprophylaxis at cesarean
      delivery with intermittent pneumatic compression. METHODS: A decision tree model
      using Markov analysis was developed to compare two approaches to perioperative
      care at the time of cesarean delivery: 1) no use of perioperative
      thromboprophylaxis and 2) the use of intermittent pneumatic compression for
      thromboprophylaxis at the time of cesarean delivery. Postcesarean deep venous
      thrombosis was estimated to occur in 0.7% of patients (75% of whom were
      asymptomatic), and result in a 9% chance of postthrombotic syndrome. Mechanical
      prophylaxis was assumed to decrease the risk of deep venous thrombosis by 70% and
      to cost 120 dollars. Probability of morbidity and mortality of venous
      thromboembolism as well as anticoagulation and the costs and utilities for
      different health state were derived from published studies. Sensitivity analysis
      was performed over a wide range of variable estimates. RESULTS: Using the
      assumptions in our base case, routine thromboprophylaxis for cesarean delivery
      cost 39,545 dollars per quality-adjusted life year. One-way sensitivity analysis
      revealed that as long as the incidence of postcesarean deep venous thrombosis was
      at least 0.68%, intermittent pneumatic compression reduced the incidence of deep
      venous thrombosis by at least 50%, or the cost of intermittent pneumatic
      compression was less than 180 dollars, the cost-effectiveness of mechanical
      prophylaxis did not exceed 50,000 dollars per quality-adjusted life year.
      CONCLUSION: Mechanical thromboprophylaxis is estimated to be a cost-effective
      strategy under a wide range of circumstances.

PMID- 16946213
TI  - Postpartum maternal mortality and cesarean delivery.
AB  - OBJECTIVE: A continuous rise in the rate of cesarean delivery has been reported
      in many countries during the past decades. This trend has prompted the emergence
      of a controversial debate on the risks and benefits associated with cesarean
      delivery. Our objective was to provide a valid estimate of the risk of postpartum
      maternal death directly associated with cesarean as compared with vaginal
      delivery. METHODS: A population-based case-control study was designed, with
      subjects selected from recent nationwide surveys in France. To control for
      indication bias, maternal deaths due to antenatal morbidities were excluded. For
      the 5-year study period 1996-2000, 65 cases were included. The control group was
      selected from the 1998 French National Perinatal Survey and included 10,244
      women. Multivariable logistic regression analysis was used to adjust for
      confounders. RESULTS: After adjustment for potential confounders, the risk of
      postpartum death was 3.6 times higher after cesarean than after vaginal delivery
      (odds ratio 3.64 95% confidence interval 2.15-6.19). Both prepartum and
      intrapartum cesarean delivery were associated with a significantly increased
      risk. Cesarean delivery was associated with a significantly increased risk of
      maternal death from complications of anesthesia, puerperal infection, and venous
      thromboembolism. The risk of death from postpartum hemorrhage did not differ
      significantly between vaginal and cesarean deliveries. CONCLUSION: Cesarean
      delivery is associated with an increased risk of postpartum maternal death.
      Knowledge of the causes of death associated with this excess risk informs
      contemporary discussion about cesarean delivery on request and should inform
      preventive strategies.

PMID- 16946214
TI  - Cumulative economic implications of initial method of delivery.
AB  - OBJECTIVE: To examine the cumulative costs of hospital care in the first and
      subsequent pregnancies associated with different methods in the initial delivery
      of nulliparous women. METHODS: An 18-year population-based cohort study (1985
      2002) using the Nova Scotia Atlee Perinatal Database compared cumulative delivery
      costs in the first and subsequent pregnancies. Women were identified by initial
      method of delivery for nulliparous women with singleton cephalic presentation at
      term undergoing spontaneous or induced labor for planned vaginal delivery, and
      for nulliparous women undergoing cesarean delivery without labor. Costs that were
      assessed included nursing hours in antepartum, labor and delivery, postpartum and
      neonatal intensive care units, physician costs, labor induction agents,
      consumables, and costs for postpartum hysterectomy, tubal ligation, and
      dilatation and curettage. RESULTS: A total of 27,613 pregnancies satisfied
      inclusion and exclusion criteria. When cumulative costs by type of labor at first
      delivery were considered, induction of labor (7,220 dollars) was more costly than
      spontaneous onset of labor (6,919 dollars, P = .006). The cumulative costs of
      assisted vaginal delivery at first delivery (7,288 dollars) and cesarean delivery
      in labor at first delivery (9,524 dollars) were similar in magnitude and were
      higher than spontaneous vaginal delivery at first delivery (P < .001). Cesarean
      delivery in labor in the first delivery was the most costly type of delivery
      (9,524 dollars), and the differences in cost increased with increasing number of
      deliveries (P < .05). CONCLUSION: Cesarean delivery in labor in the first
      delivery is associated with increased cumulative costs compared with other
      methods of delivery, regardless of the number or type of subsequent deliveries.

PMID- 16946215
TI  - Determinants of perinatal mortality and serious neonatal morbidity in the second
      twin.
AB  - OBJECTIVE: To identify potential determinants of perinatal mortality and neonatal
      morbidity among second twins relative to first twins. METHODS: A retrospective
      cohort design was used to study twin deliveries in Nova Scotia from 1988 to 2002.
      Monoamniotic or conjoined twins and twin pairs with major congenital anomaly or
      antepartum fetal death of either twin were excluded. The primary outcome was a
      composite measure of perinatal mortality and neonatal morbidity, including birth
      asphyxia, respiratory distress, neonatal trauma, and infection. Risk of adverse
      outcome of second twins relative to first-born co-twins was determined by matched
      pair analysis. RESULTS: Of 1,542 twin pairs, the second twin was at greater risk
      of composite adverse outcome (relative risk [RR] 1.62, 95% confidence interval
      [CI] 1.38-1.9) than the first twin. This excess risk was evident independent of
      presentation, chorionicity, or infant sex but was associated with planned vaginal
      delivery, birth weight discordance, and prolonged interdelivery interval. Term
      second twins were less likely to suffer excess morbidity with elective cesarean
      (RR 1.0, 95% CI 0.14-7.10) than with planned vaginal delivery (RR 3.0, 95% CI
      1.47-6.11). The major contributors to neonatal morbidity in the second twin were
      birth asphyxia at 37 weeks or later and respiratory distress syndrome at less
      than 37 weeks. CONCLUSION: The second twin is at greater risk of adverse
      perinatal outcome than the first twin, independent of presentation, chorionicity,
      or infant sex. Planned vaginal delivery, birth weight discordance, and prolonged
      interdelivery interval increase this infant risk. Elective cesarean delivery at
      term may improve perinatal outcome for the second twin. However, the number of
      cesarean births required to prevent one case of composite adverse outcome,
      assuming causality, was 33.

PMID- 16946216
TI  - Effects of dietary calcium intervention on adolescent mothers and newborns: A
      randomized controlled trial.
AB  - OBJECTIVE: To evaluate the effects of dietary calcium (Ca) intervention on
      adolescent pregnant mothers and their newborns. METHODS: Seventy-two pregnant
      adolescent mothers were randomized into one of 3 groups: control, orange juice
      fortified with calcium, and dairy. The orange juice and dairy groups were
      required to take more than 1,200 mg Ca. Calcium tablets were added for those not
      able to meet required Ca. Maternal and infant weight, length, and blood pressure
      (BP) were recorded. Maternal dietary records were evaluated. Mother's blood was
      drawn for serum Ca, phosphate (P), magnesium (Mg), and vitamin 25-hydroxyvitamin
      D (D). Cord blood was collected for serum Ca and D. Newborn total body Ca was
      determined. RESULTS: All mothers were similar in weight, height, and BP. Mothers
      in the orange juice plus calcium and dairy groups had higher intakes of Ca (1,472
      mg and 1,771 mg) than controls (862 mg). One half of the mothers in the orange
      juice plus calcium group required Ca tablets. Mothers in the dairy group had
      higher intakes of P, D, and Mg, higher serum folate and D, and higher cord D
      levels. Mothers in the orange juice plus calcium group had higher serum P but
      lower serum folate and D. Infants (3,517+/-273 g) in the dairy group were heavier
      than infants in the control (3,277+/-177 g) and orange juice plus calcium
      (3,292+/-165 g) groups. Infants in the dairy group had higher total body calcium
      than control infants. CONCLUSION: Calcium diet supplemented with dairy products
      during adolescent pregnancy resulted in higher maternal vitamin D and folate
      serum levels and higher newborn weight and bone mineralization compared with
      controls.

PMID- 16946217
TI  - Accuracy of ultrasonography and magnetic resonance imaging in the diagnosis of
      placenta accreta.
AB  - BACKGROUND: The incidence of placenta accreta has increased dramatically over the
      last three decades, in concert with the increase in the cesarean delivery rate.
      Optimal management requires accurate prenatal diagnosis. The purpose of this
      study was to determine the precision and reliability of ultrasonography and
      magnetic resonance imaging (MRI) in diagnosing placenta accreta. METHODS: A
      historical cohort study was performed with information gathered from our
      obstetric, radiologic, and pathology databases. Records from January 2000 to June
      2005 were reviewed to identify patients with a diagnosis of placenta previa, low
      lying placenta with a prior cesarean delivery, or history of a myomectomy to
      determine the accuracy of pelvic ultrasonography in the diagnosis of placenta
      accreta. The records of those considered to be suspicious for placenta accreta
      and subsequently referred for additional confirmation by MRI were also analyzed.
      The sonographic and MRI diagnoses were compared with the final pathologic or
      operative findings or with both. RESULTS: Of the 453 women with placenta previa,
      previous cesarean delivery and low-lying anterior placenta, or previous
      myomectomy, 39 had placenta accreta confirmed by pathological examination.
      Ultrasonography accurately predicted placenta accreta in 30 of 39 of women and
      correctly ruled out placenta accreta in 398 of 414 without placenta accreta
      (sensitivity 0.77, specificity 0.96). Forty-two women underwent MRI evaluation
      because of findings suspicious or inconclusive of placenta accreta by
      ultrasonography. Magnetic resonance imaging accurately predicted placenta accreta
      in 23 of 26 cases with placenta accreta and correctly ruled out placenta accreta
      in 14 of 14 (sensitivity 0.88, specificity 1.0). CONCLUSION: A two-stage protocol
      for evaluating women at high risk for placenta accreta, which uses
      ultrasonography first, and then MRI for cases with inconclusive ultrasound
      features, will optimize diagnostic accuracy.

PMID- 16946218
TI  - Misoprostol administered by epithelial routes: Drug absorption and uterine
      response.
AB  - OBJECTIVE: To quantify and compare serum levels and uterine effects following
      vaginal (dry), vaginal (moistened), buccal, and rectal misoprostol
      administration. METHODS: Forty women seeking elective abortion between 6 and 12
      6/7 weeks were randomly assigned to receive 400 mug of misoprostol by one of four
      routes. A 2.5-mm pressure monitoring catheter was placed through the cervix to
      the uterine fundus to record uterine tone and activity during the 5-hour
      observation period. Serum levels of misoprostol acid were measured at 15 and 30
      minutes, then every 30 minutes. RESULTS: The four groups were similar in age,
      race or ethnicity, body mass index, parity, and gestation. Serum levels after
      vaginal, vaginal moistened and buccal administration rose gradually, peaked
      between 15 and 120 minutes and fell slowly. Vaginal and vaginal moistened routes
      produced higher peak serum levels than buccal and rectal (445.9 and 427.1
      compared with 264.8 and 202.2 pg/mL; P = .03) and higher serum concentration area
      under the curve at 5 hours (1,025.0 and 1279.4 compared with 519.6 and 312.5 pg
      hr/mL; P < .001). Uterine tone and activity, however, were similar for buccal and
      the two vaginal routes. After rectal administration, serum levels peaked earlier
      (P < .001) then dropped more abruptly, and peak uterine tone (P < .001) and total
      activity (P = .04) were lower than after the other routes. CONCLUSION: Although
      serum levels were lower for buccal compared with the vaginal routes, the three
      routes produced similar uterine tone and activity. Rectal administration produced
      lower uterine tone and activity. Vaginal serum levels were two to three and a
      half times higher than those observed in prior misoprostol pharmacokinetic
      studies.

PMID- 16946219
TI  - Amnioinfusion to facilitate external cephalic version after initial failure.
AB  - OBJECTIVE: To evaluate the effectiveness of antepartum transabdominal
      amnioinfusion to facilitate external cephalic version after initial failure.
      METHODS: Women with a structurally normal fetus in breech lie at term, with a
      failed external cephalic version and an amniotic fluid index (AFI) less than 15
      cm, were asked to participate in our study. After tocolysis with indomethacin, a
      transabdominal amnioinfusion was performed with an 18G spinal needle. Lactated
      Ringers solution was infused until the AFI reached 15 cm, with a maximum of 1 L.
      External cephalic version was performed directly afterward. RESULTS: Seven women
      participated in the study. The gestational age of the women was between 36(+4)
      and 38(+3) weeks, and three women were primiparous. The AFI ranged from 4 cm to
      13 cm. A median amount of 1,000 mL Ringers solution (range 700-1,000 mL) was
      infused per procedure. The repeat external cephalic versions after amnioinfusion
      were not successful in any of the patients. CONCLUSION: In our experience,
      amnioinfusion does not facilitate external cephalic version.

PMID- 16946220
TI  - Cost of transferring one through five embryos per in vitro fertilization cycle
      from various payor perspectives.
AB  - OBJECTIVE: We sought to examine the costs of transferring one through five
      embryos per in vitro fertilization cycle from each of three perspectives:
      society, the infertile couple, and the insurer. METHODS: Data from the 2003
      Assisted Reproductive Technology Report was used to create Markov decision
      analytic models stratified by maternal age subgroup. We modeled both total costs,
      cost-effectiveness (cost per live birth), and clinical outcomes: multiple births,
      preterm deliveries, and cerebral palsy. RESULTS: From a societal and insurer
      perspective, it was least expensive to transfer one embryo. For women aged
      younger than 35 years, it cost society 80% more to transfer five rather than one
      embryo at a time (total cost 39,212 dollars compared with 21,661 dollars). For
      women aged older than 42 years, it cost 13% more (29,102 dollars compared with
      25,723 dollars). From a parental perspective, it was least expensive to transfer
      between two and five embryos, depending on maternal age. One-embryo transfers
      markedly improved clinical outcomes. For example, two compared with one-embryo
      transfers for women aged younger than 35 years reduced preterm birth and cerebral
      palsy rates by 55% and 41%, respectively. Univariable sensitivity analysis and
      Monte Carlo simulation showed our results to be robust. CONCLUSION: Transferring
      one embryo per cycle is the least expensive strategy from a societal perspective,
      especially for younger women, yet it is the most expensive option from a parental
      perspective. To reduce in vitro fertilization-associated multiple birth rates,
      public policy must address these disparate financial incentives.

PMID- 16946221
TI  - The influence of physician race and gender on obstetrician-gynecologists' annual
      incomes.
AB  - OBJECTIVE: A study using 1998 data concluded that incomes of male and female
      obstetrician-gynecologists were essentially equivalent, after considering only
      differences in productivity. We examined the association between gender, race,
      and obstetrician-gynecologists' incomes, after correcting for productivity and
      other important practice and provider characteristics. METHODS: Survey responses
      obtained from 1992 to 2001 from 962 actively practicing obstetrician
      gynecologists and linear regression modeling were used to estimate the influence
      of race and gender on physicians' annual incomes after controlling for work
      effort, provider characteristics, and practice characteristics. RESULTS: Compared
      with white male and black female obstetrician-gynecologists, black men reported
      seeing 5% more patient visits and working 18% more hours, while white women
      reported seeing 18% fewer visits and working 10% fewer annual hours. Women were
      more likely to be nonowner employees than men. White female obstetrician
      gynecologists were less likely than the other groups to be board certified. After
      adjustment for work effort, provider characteristics, and practice
      characteristics, black men's mean reported annual income was 210,859 dollars, or
      78,905 dollars (27%) lower than that for white men (95% confidence interval [CI]
      120,082 dollars to 37,729 dollars lower; P < .001); white women's was 242,721
      dollars, or 47,043 dollars (16%) lower (95% CI 70,127 dollars to 23,958 dollars
      lower; P < .001); and black women's was 246,355 dollars, or 43,409 dollars (15%)
      lower (95% CI 92,296 dollars to 5,478 dollars higher, P = .08). CONCLUSION:
      During the 1990s, both black race and female gender were associated with
      substantially lower annual incomes among obstetrician-gynecologists. These
      findings warrant further exploration to ensure that income differences among
      physicians are not unjustly driven by race or gender.

PMID- 16946222
TI  - Chorionic villus sampling compared with amniocentesis and the difference in the
      rate of pregnancy loss.
AB  - OBJECTIVE: To compare loss rates following amniocentesis and chorionic villus
      sampling (CVS) over time. METHODS: A retrospective cohort study of all
      amniocentesis and CVS procedures resulting in a normal karyotype from 1983-2003
      at a single prenatal diagnostic referral center was conducted. Pregnancy loss
      rates for amniocentesis, CVS, and nonintervention groups (ie, those who had
      nuchal translucency screening or counseling, but no procedure) were compared
      using the chi 2 test. Year of procedure, maternal age, parity, race or ethnicity,
      and gestational age at procedure were controlled for in multivariable logistic
      regression models. RESULTS: There were 9,886 CVS and 30,893 amniocentesis
      procedures performed during the study period that resulted in a normal karyotype.
      The overall loss rates were 3.12% for CVS and 0.83% for amniocentesis (P < .001).
      When examined by 5-year intervals, there was a statistically significant decrease
      in the CVS loss rate (P < .001) and a nonsignificant lesser decrease in the loss
      rate for amniocentesis over time. Although the pregnancy loss rate from CVS over
      the entire study period was higher than from amniocentesis (adjusted odds ratio
      4.23, 95% confidence interval 2.29-7.81), in the most recent time period, 1998 to
      2003, there was no difference between the two procedures (adjusted odds ratio
      1.03, 95% confidence interval 0.23-4.52). CONCLUSION: The loss rates for both
      amniocentesis and CVS at our institution have decreased over time. Because the
      decrease in loss rate for CVS has been greater, there is no longer a
      statistically significant difference between the two. These results are
      informative in both patient counseling and establishing widespread prenatal
      diagnostic and screening programs.

PMID- 16946223
TI  - Kinetics of betamethasone and fetal cardiovascular adverse effects in pregnant
      sheep after different doses.
AB  - OBJECTIVE: To study the pharmacokinetics of different betamethasone doses and
      preparations used to enhance fetal lung maturation in the maternal and fetal
      circulation of sheep and the adverse effects on fetal blood pressure. METHODS:
      Doses of 170 (n = 6) and 110 microg/kg (n = 6) betamethasone phosphate equivalent
      to 12 or 8 mg, respectively, administered to a 70 kg pregnant woman or 170
      microg/kg (n = 6) of a depot formulation (50% betamethasone phosphate and 50%
      betamethasone acetate) were injected intramuscularly to chronically instrumented
      pregnant sheep. RESULTS: Both betamethasone preparations produced highest
      maternal concentrations after 15 min followed by an exponential decline with a
      t(1/2) of about 3 hours. The drug fell below the limit of detection at 8 to 12
      hours. Betamethasone was first detectable in the fetal circulation at 1 hour,
      peaked at 3 hours, and decreased below the limit of detection at 8 hours
      independently of the dose or preparation. Maternal and fetal betamethasone
      concentrations achieved with the phosphate and acetate formulation were one half
      of those obtained with betamethasone phosphate, suggesting that very little
      betamethasone is released from the acetate within the first 8 hours when the
      effect on lung maturation is needed. Betamethasone led to a maximal increase of
      mean fetal blood pressure from 42+/-1 to 51+/-1 mm Hg (P < .05) and did not
      differ between the doses and preparations, although plasma concentrations showed
      a clear dose-concentration relationship. CONCLUSION: The doses of betamethasone
      used in obstetrics are supramaximal in terms of cardiovascular effects in sheep.
      Risk-benefit studies are needed to find the effective steroid dose with the least
      adverse effects.

PMID- 16946224
TI  - Maternal race, procedures, and infant birth weight in type 2 and gestational
      diabetes.
AB  - OBJECTIVE: To examine the relation between race and cesarean delivery,
      episiotomy, and low birth weight infants in pregnancies with type 2 and
      gestational diabetes mellitus and to identify factors that might explain racial
      differences. METHODS: Population-based, cross-sectional study of 1999-2004
      Maryland hospital discharge data. Hospitalizations for delivery of pregnancies
      with type 2 and gestational diabetes mellitus were identified and matched to
      infants. The independent variable was maternal race. Dependent variables were
      cesarean delivery, episiotomy, and low infant birth weight. Stepwise logistic
      regression models were developed to estimate the independent effect of race on
      use of each procedure and infant birth weight, after adjusting for
      sociodemographic, hospital, and clinical factors. RESULTS: We examined 6,310
      deliveries for pregnancies with type 2 (15%) and gestational (85%) diabetes.
      Before adjustment, black race was associated with a higher odds of cesarean
      delivery (odds ratio [OR] 1.40, 95% confidence interval [CI] 1.24-1.58) and low
      birth weight infants (OR 1.94, 95% CI 1.57-2.40) compared with white race.
      Adjustment for racial differences in preeclampsia and fetal heart rate
      abnormalities accounted for a modest degree of the racial variation in outcomes.
      With full adjustment, black race was still associated with a higher odds of
      cesarean delivery (OR 1.38, 95% CI 1.20-1.60) and low birth weight (OR 1.81, 95%
      CI 1.41-2.34) and a lower odds of episiotomy (OR 0.45, 95% CI 0.36-0.57).
      CONCLUSION: In pregnancies with diabetes, adjustment for sociodemographic,
      hospital, and clinical factors only partially explains racial differences in
      procedure use and infant low birth weight.

PMID- 16946225
TI  - Gestational weight gain and adverse neonatal outcome among term infants.
AB  - OBJECTIVE: To examine the relationship between gestational weight gain and
      adverse neonatal outcomes among infants born at term (37 weeks or more). METHODS:
      This was a retrospective cohort study of 20,465 nondiabetic, term, singleton
      births. We performed univariable and multivariable analyses of the associations
      between gestational weight gain and neonatal outcomes. We categorized gestational
      weight gain by the Institute of Medicine guidelines as well as extremes of
      gestational weight gain (less than 7 kg and more than 18 kg). RESULTS:
      Gestational weight gain above the Institute of Medicine guidelines was more
      common than gestational weight gain below (43.3% compared with 20.1%). In
      multivariable analyses, gestational weight gain above guidelines was associated
      with a low 5-minute Apgar score (adjusted odds ratio [AOR] 1.33, 95% confidence
      interval [CI] 1.01-1.76), seizure (AOR 6.50, 95% CI 1.43-29.65), hypoglycemia
      (AOR 1.52, 95% CI 1.06-2.16), polycythemia (AOR 1.44, 95% CI 1.06-1.94), meconium
      aspiration syndrome (AOR 1.79, 95% CI 1.12-2.86), and large for gestational age
      (AOR 1.98, 95% CI 1.74-2.25) compared with women within weight gain guidelines.
      Gestational weight gain below guidelines was associated with decreased odds of
      neonatal intensive care unit admission (AOR 0.66, 95% CI 0.46-0.96) and increased
      odds of small for gestational age (SGA; AOR 1.66, 95% CI 1.44-1.92). Gestational
      weight gain less than 7 kg was associated with increased risk of seizure,
      hospital stay more than 5 days, and SGA. Gestational weight gain more than 18 kg
      was associated with assisted ventilation, seizure, hypoglycemia, polycythemia,
      meconium aspiration syndrome, and large for gestational age. CONCLUSION:
      Gestational weight gain above guidelines was common and associated with multiple
      adverse neonatal outcomes, whereas gestational weight gain below guidelines was
      only associated with SGA status. Public health efforts among similar populations
      should emphasize prevention of excessive gestational weight gain.

PMID- 16946226
TI  - Fetal and neonatal outcomes of diabetic pregnancies.
AB  - OBJECTIVE: To estimate whether the incidences of adverse fetal and neonatal
      outcomes in infants of mothers with preexisting types 1 and 2 diabetes 1) differ
      from infants of nondiabetic mothers in Nova Scotia (NS); and 2) have changed
      between 1988 and 2002. METHODS: Population-based cohort study using the NS Atlee
      Perinatal Database, a well-validated source of standardized clinical information.
      RESULTS: A total of 516 infants of diabetic mothers and 150,589 infants of
      nondiabetic mothers from singleton pregnancies were studied. Infants of diabetic
      mothers had significantly higher rates of perinatal mortality (17.4/1,000
      compared with 5.9/1,000, relative risk [RR] 3.01, 95% confidence interval [CI]
      1.55-5.84), major congenital anomaly (9.1% compared with 3.1%, RR 2.97, 95% CI
      2.25-3.90), and large for gestational age birth (LGA, more than 90th percentile
      weight for gestational age) (45.2% compared with 12.6%, RR 3.59, 95% CI 3.26
      3.95) than infants of nondiabetic mothers. In infants of diabetic mothers, there
      was no improvement in perinatal mortality (23.4/1,000 in 1988-1995 compared with
      11.5/1000 in 1996-2002, P = .340), incidence of LGA (48.0% in 1988-1995 compared
      with 42.3% in 1996-2002, P = .237), or rate of major congenital anomaly (8.2% in
      1988-1995 compared with 10.0% in 1996-2002, P = .560). Diabetes remained an
      independent risk factor for LGA infants and major congenital anomaly after
      adjusting for possible confounders. CONCLUSION: Rates of adverse neonatal
      outcomes are 3-9 times greater in infants of diabetic mothers compared with those
      of nondiabetic mothers. There were no significant improvements in rates of
      perinatal mortality, congenital anomaly, or LGA birth in infants of diabetic
      mothers in 1996-2002 compared with 1988-95.

PMID- 16946227
TI  - Human chorionic gonadotropin and plasma protein-A in alpha0-thalassemia
      pregnancies.
AB  - OBJECTIVE: Maternal serum free beta-human chorionic gonadotropin (beta-hCG) and
      pregnancy-associated plasma protein-A (PAPP-A) have been used effectively in the
      screening of Down syndrome in the first trimester. In this study, we aim to
      measure the value of first-trimester maternal serum free beta-hCG and PAPP-A as
      predictors of homozygous alpha0-thalassemia-affected pregnancies. METHODS: Free
      beta-hCG and PAPP-A concentrations were measured in stored maternal serum samples
      obtained at 12 weeks of gestation from 22 women with fetuses affected by
      homozygous alpha0-thalassemia and from 436 controls matched for maternal age,
      ethnicity, and weight, as well as gestation at blood sampling. RESULTS: Maternal
      serum concentration of free beta-hCG was significantly increased in women with
      pregnancies affected by homozygous alpha0-thalassemia than in controls (P =
      .001). Concentrations of PAPP-A did not differ between the cases affected by
      homozygous alpha0-thalassemia and the controls (P = .652). CONCLUSION:
      Pregnancies affected by homozygous alpha0-thalassemia are associated with
      increased maternal serum free beta-hCG at 11-14 weeks of gestation. This serum
      analyte alone may not be clinically useful as a predictor of pregnancies affected
      by homozygous alpha0-thalassemia. However, the absence of ultrasound features of
      fetal anemia and hydropic changes, together with normal maternal serum free beta
      hCG and PAPP-A in the first trimester, will be reassuring signs of normality for
      fetuses at risk of homozygous alpha0-thalassemia and, hence, enable women to
      avoid invasive tests in unaffected pregnancies.

PMID- 16946228
TI  - Intrapartum electronic fetal heart rate monitoring and the prevention of
      perinatal brain injury.
AB  - OBJECTIVE: Electronic fetal heart rate monitoring (EFM) is the most widely used
      method of intrapartum surveillance, and our objective is to review its ability to
      prevent perinatal brain injury and death. DATA SOURCES: Studies that quantified
      intrapartum EFM and its relation to specific neurologic outcomes (seizures,
      periventricular leukomalacia, cerebral palsy, death) were eligible for inclusion.
      MEDLINE was searched from 1966 to 2006 for studies that examined the relationship
      between intrapartum EFM and perinatal brain injury using these MeSH and text
      words: "cardiotocography," "electronic fetal monitoring," "intrapartum fetal
      heart rate monitoring," "intrapartum fetal monitoring," and "fetal heart rate
      monitoring." METHODS OF STUDY SELECTION: This search strategy identified 1,628
      articles, and 41 were selected for further review. Articles were excluded for the
      following reasons: in case reports, letters, commentaries, and review articles,
      intrapartum EFM was not quantified, or specific perinatal neurologic morbidity
      was not measured. Three observational studies and a 2001 meta-analysis of 13
      randomized controlled trials were selected for determination of the effect of
      intrapartum EFM on perinatal brain injury. TABULATION, INTEGRATION, AND RESULTS:
      Electronic fetal monitoring was introduced into widespread clinical practice in
      the late 1960s based on retrospective studies comparing its use to historical
      controls where auscultation was performed in a nonstandardized manner. Case
      control studies have shown correlation of EFM abnormalities with umbilical artery
      base excess, but EFM was not able to identify cerebral white matter injury or
      cerebral palsy. Of 13 randomized controlled trials, one showed a significant
      decrease in perinatal mortality with EFM compared with auscultation. Meta
      analysis of the randomized controlled trials comparing EFM with auscultation have
      found an increased incidence of cesarean delivery and decreased neonatal seizures
      but no effect on the incidence of cerebral palsy or perinatal death. CONCLUSION:
      Although intrapartum EFM abnormalities correlate with umbilical cord base excess
      and its use is associated with decreased neonatal seizures, it has no effect on
      perinatal mortality or pediatric neurologic morbidity.

PMID- 16946229
TI  - Asthma and pregnancy.
AB  - Asthma complicates 4-8% of pregnancies. Mild and well-controlled moderate asthma
      can be associated with excellent maternal and perinatal pregnancy outcomes.
      Severe and poorly controlled asthma may be associated with increased prematurity,
      need for cesarean delivery, preeclampsia, growth restriction, other perinatal
      complications, as well as maternal morbidity and mortality. Optimal management of
      asthma during pregnancy includes objective monitoring of lung function, avoiding
      or controlling asthma triggers, patient education, and individualized
      pharmacologic therapy. Those with persistent asthma should be monitored by peak
      expiratory flow rate, spirometry to measure the forced expiratory volume in 1
      second, or both. Step-care therapeutic approach uses the least amount of drug
      intervention necessary to control a patient's severity of asthma. Inhaled
      corticosteroids are the preferred treatment for the management of all levels of
      persistent asthma during pregnancy. It is safer for pregnant women with asthma to
      be treated with asthma medications than it is for them to have asthma symptoms
      and exacerbations. The ultimate goal of asthma therapy is maintaining adequate
      oxygenation of the fetus by prevention of hypoxic episodes in the mother. Asthma
      exacerbations should be aggressively managed, with a goal of alleviating asthma
      symptoms and attaining peak expiratory flow rate or forced expiratory volume in 1
      second of 70% predicted or more. Pregnancies complicated by moderate or severe
      asthma may benefit from ultrasound for fetal growth and accurate dating and
      antenatal assessment of fetal well-being. Asthma medications should be continued
      during labor, and parturients should be encouraged to breastfeed.

PMID- 16946230
TI  - One cheer for choice.

PMID- 16946231
TI  - Letter from Madagascar.

PMID- 16946232
TI  - Refusals by pharmacists to dispense emerging contraception: a critique.

PMID- 16946233
TI  - Placenta previa, placenta accreta, and vasa previa.

PMID- 16946234
TI  - Can a 29% cesarean delivery rate possibly be justified?

PMID- 16946235
TI  - ACOG Committee Opinion No. 344: Human papillomavirus vaccination.

PMID- 16946236
TI  - Evidence for the participation of the proteasome in symbiont-induced tissue
      morphogenesis.

PMID- 16946237
TI  - Characterization and role of p53 family members in the symbiont-induced
      morphogenesis of the Euprymna scolopes light organ.
AB  - Within hours of hatching, the squid Euprymna scolopes forms a specific light
      organ symbiosis with the marine luminous bacterium Vibrio fischeri. Interactions
      with the symbiont result in the loss of a complex ciliated epithelium dedicated
      to promoting colonization of host tissue, and some or all of this loss is due to
      widespread, symbiont-induced apoptosis. Members of the p53 family, including p53,
      p63, and p73, are conserved across broad phyletic lines and p63 is thought to be
      the ancestral gene. These proteins have been shown to induce apoptosis and
      developmental morphogenesis. In this study, we characterized p63-like transcripts
      from mRNA isolated from the symbiotic tissues of E. scolopes and described their
      role in symbiont-induced morphogenesis. Using degenerate RT-PCR and RACE PCR, we
      identified two p63-like transcripts encoding proteins of 431 and 567 amino acids.
      These transcripts shared identical nucleotides where they overlapped, suggesting
      that they are splice variants of the same gene. Immunocytochemistry and Western
      blots using an antibody specific for E. scolopes suggested that the p53 family
      members are activated in cells of the symbiont-harvesting structures of the
      symbiotic light organ. We propose that once the symbiosis is initiated, a
      symbiont-induced signal activates p53 family members, inducing apoptosis and
      developmental morphogenesis of the light organ.

PMID- 16946238
TI  - Two atypical carbonic anhydrase homologs from the planula larva of the
      scleractinian coral Fungia scutaria.
AB  - In cnidarians, the enzyme carbonic anhydrase (CA) is important to inorganic
      carbon (Ci) flux in processes including calcification and dinoflagellate symbiont
      photosynthesis. Although CA is known to function in Ci delivery to symbionts in
      adults with mature symbioses, it is not known when CA becomes active in this
      capacity during the onset of symbiosis in developing hosts. We identified two CA
      cDNA sequences from the planula larvae of the Hawaiian scleractinian coral Fungia
      scutaria. Expression of these larval CAs did not differ between infected and
      uninfected larvae or vary over the course of infection. Bioinformatic analyses of
      the two homologs showed that the sequences are unusually short and are missing
      some residues that support active site structure in other CAs. This is the first
      description of a short form of CA. Phylogenetic analyses of the larval CAs
      grouped them with membrane-bound homologs from vertebrates. Studies in other
      calcifying cnidarians have identified membrane-associated CAs as functioning in
      calcification, and therefore the two larval CAs could play a role in the onset of
      calcification during metamorphosis. A longer CA isoform was amplified from adult
      F. scutaria cDNA but not from larvae, suggesting that the longer form is not
      expressed in larvae. The longer form grouped with cytosolic CAs including a
      symbiotic anemone homolog implicated in Ci delivery to dinoflagellate symbionts.
      The apparent absence of this "symbiosis" CA in larvae suggests that the Ci supply
      mechanism is not active during the initial onset of the association.

PMID- 16946239
TI  - Effects of beta-catenin on dendritic morphology and simulated firing patterns in
      cultured hippocampal neurons.
AB  - Beta-catenin is an intracellular signaling molecule that has been shown to be
      important in activity-dependent dendritic morphogenesis. Here, we investigate the
      detailed morphological changes elicited in dendritic arbors of cultured
      hippocampal neurons by overexpression of beta-catenin, and we simulate the
      electrophysiological consequences of these changes. Compared to control neurons,
      cells overexpressing beta-catenin have dendritic arbors with significantly
      greater surface area and more branches, as well as different topological
      characteristics. To investigate possible effects of beta-catenin expression on
      the electrophysiological properties of neurons, we converted confocal images of
      neurons expressing beta-catenin into computational simulator formats using
      parameters that evenly distributed voltage-dependent channels across the cells'
      membranes. In simulated current clamp experiments, somata were injected with a
      normalized current such that the observed electrophysiological differences in the
      neurons would be due only to morphological differences. We found that the
      morphology of beta-catenin-expressing neurons contributes to significantly
      smaller action potential amplitude and greater sensitivity than seen in control
      neurons. As a consequence, beta-catenin-expressing neurons tended to exhibit
      higher spike rates and needed less excitation to induce firing. These findings
      show that beta-catenin, by modifying dendritic arborization, could have profound
      influences on the electrophysiological behavior of neurons.

PMID- 16946240
TI  - Impact of exposure to bacteria on metabolism in the penaeid shrimp Litopenaeus
      vannamei.
AB  - We hypothesized that aggregation of bacteria and hemocytes at the gill, which
      occurs as part of the shrimp's antibacterial immune defenses, would impair normal
      respiratory function and thereby disrupt aerobic metabolism. Changes in oxygen
      uptake and lactate accumulation were determined in Litopenaeus vannamei, the
      Pacific white shrimp, following injection with either saline (control) or a
      strain of the gram-negative bacterium Vibrio campbellii that is pathogenic in
      crustaceans. The rate of oxygen uptake was determined during the first 4 h after
      injection and after 24 h. Injection of bacteria decreased oxygen uptake by 27%
      (from 11.0 to 8.2 micromol g-1 h-1) after 4 h, while saline-injected shrimp
      showed no change. Decreased oxygen uptake persisted 24 h after Vibrio injection.
      In well-aerated water, resting whole-animal lactic acid levels increased in
      shrimp injected with bacteria (mean=2.59 micromol lactate g-1+/-0.39 SEM, n=8)
      compared to saline-injected control shrimp, but this difference did not persist
      at 24 h. Exposure to hypercapnic hypoxia (PCO2=1.8 kPa, PO2=6.7 kPa) also
      resulted in significant whole-body lactic acid differences (mean=3.99 and 1.8
      micromol g-1 tissue in Vibrio and saline-injected shrimp, respectively). Our
      results support the hypothesis that the crustacean immune response against
      invading bacteria impairs normal metabolic function, resulting in depression of
      oxygen uptake and slightly increased anaerobic metabolism.

PMID- 16946241
TI  - Immune defense reduces respiratory fitness in Callinectes sapidus, the Atlantic
      blue crab.
AB  - Crustacean gills function in gas exchange, ion transport, and immune defense
      against microbial pathogens. Hemocyte aggregates that form in response to
      microbial pathogens become trapped in the fine vasculature of the gill, leading
      to the suggestion by others that respiration and ion regulation might by impaired
      during the course of an immune response. In the present study, injection of the
      pathogenic bacterium Vibrio campbellii into Callinectes sapidus, the Atlantic
      blue crab, caused a dramatic decline in oxygen uptake from 4.53 to 2.56 micromol
      g-1 h-1. This decline in oxygen uptake is associated with a large decrease in
      postbranchial PO2, from 16.2 (+/-0.46 SEM, n=7) to 13.1 kPa (+/-0.77 SEM, n=9),
      while prebranchial PO2 remains unchanged. In addition, injection of Vibrio
      results in the disappearance of a pH change across the gills, an indication of
      reduced CO2 excretion. The hemolymph hydrostatic pressure change across the gill
      circulation increases nearly 2-fold in Vibrio-injected crabs compared with a
      negligible change in pressure across the gill circulation in saline-injected,
      control crabs. This change, in combination with stability of heart rate and
      branchial chamber pressure, is indicative of a significant increase in vascular
      resistance across the gills that is induced by hemocyte nodule formation. A
      healthy, active blue crab can eliminate most invading bacteria, but the
      respiratory function of the gills is impaired. Thus, when blue crabs are engaged
      in the immune response, they are less equipped to engage in oxygen-fueled
      activities such as predator avoidance, prey capture, and migration. Furthermore,
      crabs are less fit to invade environments that are hypoxic.

PMID- 16946242
TI  - Expression profiles of Na+,K+-ATPase during acute and chronic hypo-osmotic stress
      in the blue crab Callinectes sapidus.
AB  - During acclimation to dilute seawater, the specific activity of Na+,K+-ATPase
      increases substantially in the posterior gills of the blue crab Callinectes
      sapidus. To determine whether this increase occurs through regulation of pre
      existing enzyme or synthesis of new enzyme, mRNA and protein levels were measured
      over short (<24 h) and long (18 days) time courses. Na+,K+-ATPase expression,
      both mRNA and protein, did not change during the initial 24-h exposure to dilute
      seawater (10 ppt salinity). Thus, osmoregulation in C. sapidus during acute
      exposure to low salinity likely involves either modulation of existing enzyme or
      mechanisms other than an increase in the amount of Na+,K+-ATPase enzyme. However,
      crabs exposed to dilute seawater over 18 days showed a 300% increase in Na+,K+
      ATPase specific activity as well as a 200% increase in Na+,K+-ATPase protein
      levels. Thus, it appears that the increase in Na+,K+-ATPase activity during
      chronic exposure results from the synthesis of new enzyme. The relative amounts
      of mRNA for the alpha-subunit increased substantially (by 150%) during the
      acclimation process, but once the crabs had fully acclimated to low salinity, the
      mRNA levels had decreased and were not different from levels in crabs fully
      acclimated to high salinity. Thus, there is transient induction of the Na+,K+
      ATPase mRNA levels during acclimation to dilute seawater.

PMID- 16946243
TI  - Ionic and acid-base consequences of exposure to increased salinity in the zebra
      mussel, Dreissena polymorpha.
AB  - Dreissena polymorpha, an invasive freshwater bivalve, displays physiological
      characteristics that reflect its ancestry in brackish water, yet it has limited
      ability to withstand modest increases in salinity. We examined changes in
      hemolymph ion concentrations and acid-base variables in mussels transferred to
      and incubated in 10% artificial seawater (ASW) for 7 days and then returned to
      pondwater (PW) for a further 7 days. Hemolymph was sampled (10 animals per sample
      period) every 4 h for the first 24-h incubation and at 72 h and 168 h for both
      the transfer to 10% ASW and the transfer back to PW. The initial response to
      transfer to 10% ASW was a rapid attainment of an apparent isoosmotic steady
      state, with most hemolymph ion concentrations rising and attaining steady state
      within 12 h. Hemolymph magnesium rose more slowly, and hemolymph calcium declined
      despite an increase in its concentration in the bathing medium. Hemolymph pH rose
      significantly during the first 24 h, from 7.96 to 8.25, as a result of increases
      in bicarbonate; pH subsequently returned to normal through increases in PCO2.
      When animals were returned to PW after 7 days' incubation in ASW, the response of
      the major hemolymph ions was largely the reverse of that effected by the transfer
      to ASW. Hemolymph pH was not altered significantly until after 72 h in PW, when
      declines in bicarbonate lowered the pH to 7.73. Strong ion difference (SID) was
      related significantly to hemolymph pH. Hemolymph calcium and magnesium showed a
      reciprocal relationship throughout both transfer and incubation. Solubility
      interactions between sulfate and calcium and magnesium may be important in
      determining calcium availability in solution. The Na/K ratio in hemolymph was
      maintained within relatively narrow bounds throughout the procedure and may
      contribute to the mussels' ability to volume-regulate during an osmotic
      challenge. Overall, the responses of D. polymorpha to modest changes in salinity
      were largely the result of passive processes.

PMID- 16946244
TI  - Function-dependent development in a colonial animal.
AB  - How does the way an organism functions affect its subsequent development?
      Bryozoans are colonial animals that capture suspended food particles from water
      currents they generate using crowns of ciliated tentacles (lophophores). In many
      encrusting bryozoans the water passes through and then under the lophophores
      until it exits the colony at "chimneys" where the lophophores spread apart to
      form an opening. To determine whether these water currents can induce the
      formation of new chimneys, I augmented the excurrent flow by injecting seawater
      into the colony. New chimneys began to develop near the site of seawater
      injection within as little as one to two days. New chimneys rarely began to
      develop within this time interval at control sites where I did not inject
      seawater. This shows that fluid flow controls development in an external fluid
      transport system lacking pipe-like conduits, as has been found in the vertebrate
      circulatory system, an internal fluid transport system with pipe-like conduits.
      These fluid transport systems show feedback between the way they function and
      their own development. This kind of "function-dependent development" should be
      differentiated from phenotypic plasticity, since the developing system, not the
      environment, produces the signals that induce morphological change.

PMID- 16946245
TI  - Sponge systematics by starfish: predators distinguish cryptic sympatric species
      of Caribbean fire sponges, Tedania ignis and Tedania klausi n. sp. (Demospongiae,
      Poecilosclerida).
AB  - Tedania ignis (Duchassaing and Michelotti, 1864), the fire sponge, is common
      throughout the tropical western Atlantic, and is a popular species for studies of
      ecology, larval biology, and chemistry. T. ignis is readily consumed by seagrass
      dwelling starfish, and so finding sponges similar to this species in a seagrass
      meadow provoked closer scrutiny. A variety of ecological, morphological, and
      molecular traits consistently and unambiguously distinguish T. ignis from a
      cryptic sympatric congener, here described as Tedania klausi, n. sp. Starfish
      that consume T. ignis reject T. klausi, and angelfish consume T. klausi less
      quickly. In Belize, T. ignis individuals transplanted to a seagrass meadow
      inhabited by T. klausi were consumed by starfish, and individuals of T. klausi
      transplanted to a mangrove-lined creek in which T. ignis flourishes, died. In
      Panama, many individuals of T. klausi were diseased in May 2004, while adjacent
      individuals of T. ignis were unaffected. Spicule types are the same in the two
      forms, and sizes overlap; but within individuals, the relative sizes of styles
      and tylotes differ in a pattern that distinguishes the two forms. Comparison of
      DNA sequences for mitochondrial cytochrome c oxidase subunit I (COI) revealed
      that 8 single nucleotide mutations consistently differ between the two forms
      regardless of habitat (seagrass vs. mangrove) and geographically separated sites
      (Belize vs. Panama).

PMID- 16946246
TI  - Hypermutable bacteria isolated from humans--a critical analysis.
AB  - Hypermutable bacteria of several species have been described among isolates
      recovered from humans over the last decade. Interpretation of the literature in
      this area is complicated by diversity in the determination and definition of
      hypermutability, and this review outlines the different methods used.
      Inactivation of the mismatch repair gene mutS is often implicated in the mutator
      phenotype; the reported effect of mutS inactivation on mutation frequency varies
      widely between species, from under 10-fold to nearly 1,000-fold, but also varies
      among different reports on the same species. Particularly high proportions of
      mutators have been reported among Pseudomonas aeruginosa and other species in the
      cystic fibrosis lung, epidemic serogroup A Neisseria meningitidis, and
      Helicobacter pylori. Aspects of the biology of these infections that could be
      relevant to hypermutability are discussed, and some future directions that may
      increase our understanding of mutators among bacteria isolated from humans are
      considered.

PMID- 16946247
TI  - Rho-dependent terminators and transcription termination.
AB  - Rho-dependent transcription terminators participate in sophisticated genetic
      regulatory mechanisms, in both bacteria and phages; they occur in regulatory
      regions preceding the coding sequences of genes and within coding sequences, as
      well as at the end of transcriptional units, to prevent readthrough
      transcription. Most Rho-dependent terminators have been found in enteric
      bacteria, but they also occur in Gram-positive bacteria and may be widespread
      among bacteria. Rho-dependent termination requires both cis-acting elements, on
      the mRNA, and trans-acting factors. The only cis-acting element common to Rho
      dependent terminators is richness in rC residues. Additional sequence elements
      have been observed at different Rho termination sites. These 'auxiliary elements'
      may assist in the termination process; they differ among terminators, their
      occurrence possibly depending on the function and sequence context of the
      terminator. Specific nucleotides required for termination have also been
      identified at Rho sites. Rho is the main factor required for termination; it is a
      ring-shaped hexameric protein with ATPase and helicase activities. NusG, NusA and
      NusB are additional factors participating in the termination process. Rho
      dependent termination occurs by binding of Rho to ribosome-free mRNA, C-rich
      sites being good candidates for binding. Rho's ATPase is activated by Rho-mRNA
      binding, and provides the energy for Rho translocation along the mRNA;
      translocation requires sliding of the message into the central hole of the
      hexamer. When a polymerase pause site is encountered, the actual termination
      occurs, and the transcript is released by Rho's helicase activity. Many aspects
      of this process are still being studied. The isolation of mutants suppressing
      termination, site-directed mutagenesis of cis-acting elements in Rho-dependent
      termination, and biochemistry, are and will be contributing to unravelling the
      still undefined aspects of the Rho termination machinery. Analysis of the more
      sophisticated regulatory mechanisms relying on Rho-dependent termination may be
      crucial in identifying new essential elements for termination.

PMID- 16946248
TI  - Microdiesel: Escherichia coli engineered for fuel production.
AB  - Biodiesel is an alternative energy source and a substitute for petroleum-based
      diesel fuel. It is produced from renewable biomass by transesterification of
      triacylglycerols from plant oils, yielding monoalkyl esters of long-chain fatty
      acids with short-chain alcohols such as fatty acid methyl esters and fatty acid
      ethyl esters (FAEEs). Despite numerous environmental benefits, a broader use of
      biodiesel is hampered by the extensive acreage required for sufficient production
      of oilseed crops. Therefore, processes are urgently needed to enable biodiesel
      production from more readily available bulk plant materials like sugars or
      cellulose. Toward this goal, the authors established biosynthesis of biodiesel
      adequate FAEEs, referred to as Microdiesel, in metabolically engineered
      Escherichia coli. This was achieved by heterologous expression in E. coli of the
      Zymomonas mobilis pyruvate decarboxylase and alcohol dehydrogenase and the
      unspecific acyltransferase from Acinetobacter baylyi strain ADP1. By this
      approach, ethanol formation was combined with subsequent esterification of the
      ethanol with the acyl moieties of coenzyme A thioesters of fatty acids if the
      cells were cultivated under aerobic conditions in the presence of glucose and
      oleic acid. Ethyl oleate was the major constituent of these FAEEs, with minor
      amounts of ethyl palmitate and ethyl palmitoleate. FAEE concentrations of 1.28 g
      l(-1) and a FAEE content of the cells of 26 % of the cellular dry mass were
      achieved by fed-batch fermentation using renewable carbon sources. This novel
      approach might pave the way for industrial production of biodiesel equivalents
      from renewable resources by employing engineered micro-organisms, enabling a
      broader use of biodiesel-like fuels in the future.

PMID- 16946249
TI  - Prediction of whole-genome DNA-DNA similarity, determination of G+C content and
      phylogenetic analysis within the family Pasteurellaceae by multilocus sequence
      analysis (MLSA).
AB  - Genome predictions based on selected genes would be a very welcome approach for
      taxonomic studies, including DNA-DNA similarity, G+C content and representative
      phylogeny of bacteria. At present, DNA-DNA hybridizations are still considered
      the gold standard in species descriptions. However, this method is time-consuming
      and troublesome, and datasets can vary significantly between experiments as well
      as between laboratories. For the same reasons, full matrix hybridizations are
      rarely performed, weakening the significance of the results obtained. The authors
      established a universal sequencing approach for the three genes recN, rpoA and
      thdF for the Pasteurellaceae, and determined if the sequences could be used for
      predicting DNA-DNA relatedness within the family. The sequence-based similarity
      values calculated using a previously published formula proved most useful for
      species and genus separation, indicating that this method provides better
      resolution and no experimental variation compared to hybridization. By this
      method, cross-comparisons within the family over species and genus borders easily
      become possible. The three genes also serve as an indicator of the genome G+C
      content of a species. A mean divergence of around 1 % was observed from the
      classical method, which in itself has poor reproducibility. Finally, the three
      genes can be used alone or in combination with already-established 16S rRNA, rpoB
      and infB gene-sequencing strategies in a multisequence-based phylogeny for the
      family Pasteurellaceae. It is proposed to use the three sequences as a taxonomic
      tool, replacing DNA-DNA hybridization.

PMID- 16946250
TI  - A link in transcription between the native pbpB and the acquired mecA gene in a
      strain of Staphylococcus aureus.
AB  - Conditional mutants of pbpB with an IPTG-inducible promoter were used to compare
      the effects of interrupted transcription of this gene in a meticillin-sensitive
      (MSSA) and a meticillin-resistant (MRSA) strain of Staphylococcus aureus. After 3
      h growth following the removal of IPTG, multiplication of the MSSA strain stopped
      abruptly, cells began to lyse, and membrane preparations showed greatly decreased
      quantities of penicillin-binding protein (PBP) 2. In contrast, the MRSA strain
      continued to grow for at least 20 h in the IPTG-free medium, but with gradually
      increasing doubling times, which eventually reached 180 min. The peptidoglycan
      produced during this period of extremely slow growth showed only minor
      alterations, but cells with abnormal morphology accumulated in the culture, the
      abundance of mecA transcript gradually declined, and the cellular amounts of
      PBP2A were significantly decreased. Adding back the IPTG inducer caused rapid
      resumption in the transcription of pbpB, followed by an increase in the
      transcription of mecA. No changes were detected in the transcription of pbpA, C
      and D, the determinant of 16S rRNA or the housekeeping gene pta. Promoter fusion
      experiments suggested that the transcription of the resistance gene mecA may
      respond to some regulatory signal generated in the bacteria during changes in the
      transcription of pbpB.

PMID- 16946251
TI  - Identification and characterization of msa (SA1233), a gene involved in
      expression of SarA and several virulence factors in Staphylococcus aureus.
AB  - The staphylococcal accessory regulator (sarA) plays a central role in the
      regulation of virulence in Staphylococcus aureus. To date, studies involving sarA
      have focused on its activity as a global regulator that modulates transcription
      of a wide variety of genes (>100) and its role in virulence. However, there is
      also evidence to suggest the existence of accessory elements that modulate SarA
      production and/or function. A reporter system was developed to identify such
      elements, and a new gene, msa (SA1233), mutation of which results in reduced
      expression of SarA, was identified and characterized. Additionally, it was shown
      that mutation of msa resulted in altered transcription of the accessory gene
      regulator (agr) and the genes encoding several virulence factors including alpha
      toxin (hla) and protein A (spa). However, the impact of mutating msa was
      different in the laboratory strain RN6390 and the clinical isolate UAMS-1. For
      instance, mutation of msa caused a decrease in spa and hla transcription in
      RN6390 but had a different effect in UAMS-1. The strain-dependent effects of the
      msa mutation were similar to those observed previously, which suggests that msa
      may modulate the production of specific virulence factors through its impact on
      sarA. Interestingly, sequence analysis of Msa suggests that it is a putative
      membrane protein with three membrane-spanning regions, indicating that Msa might
      interact with the environment. The findings show that msa is involved in the
      expression of SarA and several virulence factors.

PMID- 16946252
TI  - The effect of penicillin on Chlamydia trachomatis DNA replication.
AB  - Chlamydia trachomatis L2 was used to infect BGMK cells at an m.o.i. of 1.0, and
      the developmental cycle was followed by transmission electron microscopy and
      quantitative PCR (QPCR) for both chromosomal and plasmid DNA. Samples were taken
      at sequential 6 h time points. Subsequent analysis by QPCR showed that there was
      an initial slow replication period (0-18 h), followed by a rapid phase (18-36 h)
      coinciding with exponential division when the DNA doubling time was 4.6 h.
      Chromosomal DNA was amplified 100-200-fold corresponding to 7-8 generations for
      the complete developmental cycle. Penicillin (10 and 100 units ml(-1)) was added
      to cultures at 20 h post-infection (p.i.). This blocked binary fission and also
      prevented reticulate body (RB) to elementary body transition. However, exposure
      to penicillin did not prevent chromosomal or plasmid DNA replication. After a
      short lag period, following the addition of penicillin, chlamydial chromosomal
      DNA replication resumed at the same rate as in control C. trachomatis-infected
      cells. C. trachomatis-infected host cells exposed to penicillin did not lyse, but
      instead harboured large, aberrant RBs in massive inclusions that completely
      filled the cell cytoplasm. In these RBs, the DNA continued to replicate well
      beyond the end of the normal developmental cycle. At 60 h p.i. each aberrant RB
      contained a minimum of 16 chromosomal copies.

PMID- 16946253
TI  - Implication of (Mn)superoxide dismutase of Enterococcus faecalis in oxidative
      stress responses and survival inside macrophages.
AB  - The gene encoding the manganese-containing superoxide dismutase (MnSOD) of
      Enterococcus faecalis was characterized. It is transcribed monocistronically from
      an upstream promoter identified by rapid amplification of cDNA ends (RACE)-PCR. A
      sodA mutant was constructed and characterized. Growth of the mutant strain was
      not significantly different from that of its wild-type counterpart in standing
      and aerated cultures. However, the mutant was more sensitive towards menadione
      and hydroperoxide stresses. The response to H(2)O(2) stress was analysed in more
      detail, and the mode of killing of this oxidant was different under anaerobic and
      aerobic conditions. Cultures grown and challenged under anaerobic conditions were
      highly sensitive to treatment with 35 mM H(2)O(2). They were largely protected by
      the iron chelator deferoxamine, which suggested that killing was mainly due to an
      enhanced Fenton reaction. In contrast, neither strain was protected by the iron
      chelators deferoxamine and diethylenetriaminepentaacteic acid when grown and
      challenged under aerobic conditions, which suggested that inactivation of the
      cells by H(2)O(2) was due to another killing mode. The sodA mutant was more
      sensitive under these conditions, showing that MnSOD is also important for
      protecting the cells from damage under aerobic conditions. Finally, the MnSOD of
      Ent. faecalis may be considered to be a virulence factor, since survival of the
      corresponding mutant strain was highly affected inside mouse peritoneal
      macrophages.

PMID- 16946254
TI  - Irr regulates brucebactin and 2,3-dihydroxybenzoic acid biosynthesis, and is
      implicated in the oxidative stress resistance and intracellular survival of
      Brucella abortus.
AB  - Brucella abortus faces iron deprivation in both nature and the host. To overcome
      this limitation, Brucella secretes the siderophores 2,3-dihydroxybenzoic acid and
      brucebactin. A Fur-like protein named Irr has previously been characterized in B.
      abortus; this protein is present in the alpha-2 group of Proteobacteria only,
      where it negatively regulates haem biosynthesis when iron is scarce. Additional
      evidence that Irr also regulates the synthesis of both siderophores is presented
      here. Transcriptional lacZ fusion and chemical determinations revealed that Irr
      induced the transcription of the operon involved in the synthesis of the
      catecholic siderophores, which were consequently secreted under conditions of
      iron limitation. Irr was able to bind the upstream region of the operon, as shown
      by electrophoretic mobility shift assay. A B. abortus irr mutant showed higher
      intracellular haem content, catalase activity and resistance to hydrogen peroxide
      than the wild-type strain. The mutation also improved the replication and
      survival of iron-depleted bacteria within cultured mammalian cells. Although the
      pathogenesis of Brucella correlates with its ability to replicate
      intracellularly, pathogenicity was not attenuated when assayed in a murine model.

PMID- 16946255
TI  - Transcriptional profiling of Borrelia burgdorferi containing a unique bosR allele
      identifies a putative oxidative stress regulon.
AB  - Borrelia burgdorferi regulates gene expression in response to environmental
      conditions, including temperature, pH, redox potential and host factors. B.
      burgdorferi encodes a PerR homologue designated BosR, which presumably serves as
      a global regulator of genes involved in the oxidative stress response. Infectious
      B. burgdorferi strain B31 is resistant to oxidative stressors in vitro, whereas
      the non-infectious isolate was sensitive due, in part, to a point mutation that
      converts an arginine to a lysine at residue 39 of BosR. Subsequent insertional
      inactivation of this bosRR39K allele (bosRR39K : : kan(R)) restored resistance to
      oxidative stressors. These observations suggest that the B. burgdorferi non
      infectious bosRR39K : : kan(R) strain may transcribe genes that are also
      expressed in infectious B. burgdorferi cells, but are repressed in the bosRR39K
      background, thus explaining the different oxidative stress phenotypes observed
      between these isolates. To test this hypothesis, macroarray technology and
      quantitative RT-PCR were utilized to compare the transcriptional profiles from
      the isogenic bosRR39K and bosRR39K : : kan(R) isolates. Array data indicated that
      88 ORFs were significantly expressed in the absence of BosRR39K. Since most
      affected genes mapped to the chromosome, it is likely that these genes define an
      important physiologic response for B. burgdorferi. Included within the genes
      identified was the detoxification gene sodA, as well as other loci not overtly
      linked to oxidative stress. These results suggest that a putative BosR regulon,
      as defined by the bosRR39K allele, is required to combat toxic oxidative
      intermediates, but may also be involved in adaptive strategies that are
      independent of reactive oxygen species.

PMID- 16946256
TI  - Construction and characterization of a Lactococcus lactis strain deficient in
      intracellular ClpP and extracellular HtrA proteases.
AB  - A Lactococcus lactis strain deficient in both its major proteases, intracellular
      (ClpP) and extracellular (HtrA), was constructed and characterized. This strain,
      hereafter called clpP-htrA, could be obtained only by conjugation between a clpP
      donor strain and an htrA recipient strain in the NZ9000 context, allowing
      heterologous gene expression under the control of the NICE (nisin-controlled
      expression) system. The clpP-htrA double mutant showed both higher stress
      tolerance (e.g. high temperature and ethanol resistance) and higher viability
      than single clpP or htrA mutant strains. In addition, the secretion rate of two
      heterologous proteins (staphylococcal nuclease Nuc and Nuc-E7) was also higher in
      clpP-htrA than in the wild-type strain. This strain should be a useful host for
      high-level production and quality of stable heterologous proteins.

PMID- 16946257
TI  - Fermentation acids inhibit amino acid deamination by Clostridium sporogenes MD1
      via a mechanism involving a decline in intracellular glutamate rather than
      protonmotive force.
AB  - Fermentation acids inhibited the growth and ammonia production of the amino-acid
      fermenting bacterium Clostridium sporogenes MD1, but only when the pH was acidic.
      Such inhibition was traditionally explained by the ability of fermentation acids
      to act as uncouplers and decrease protonmotive force (Deltap), but C. sporogenes
      MD1 grows even if the Deltap is very low. Cell suspensions incubated with
      additional sodium chloride produced ammonia as rapidly at pH 5.0 as at pH 7.0,
      but cells incubated with additional sodium lactate were sensitive to even small
      decreases in extracellular pH. Similar results were obtained if the sodium
      lactate was replaced by sodium acetate or propionate. When extracellular pH
      declined, DeltapH increased even if sodium lactate was present. The cells
      accumulated intracellular lactate anion when the pH was acidic, and intracellular
      glutamate declined. Because amino acid deamination is linked to a transamination
      reaction involving glutamate dehydrogenase, the decrease in ammonia production
      could be explained by the decrease in intracellular glutamate. This latter
      hypothesis was consistent with the observation that extracellular glutamate
      addition restored amino acid deamination even though glutamate alone did not
      allow for the generation of ammonia.

PMID- 16946258
TI  - Trehalose metabolism is important for heat stress tolerance and spore germination
      of Botrytis cinerea.
AB  - To analyse the role of trehalose as stress protectant and carbon storage compound
      in the grey mould fungus Botrytis cinerea, mutants defective in trehalose-6
      phosphate synthase (TPS1) and neutral trehalase (TRE1) were constructed. The
      Deltatps1 mutant was unable to synthesize trehalose, whereas the Deltatre1 mutant
      showed elevated trehalose levels compared to the wild-type and was unable to
      mobilize trehalose during conidial germination. Both mutants showed normal
      vegetative growth and were not affected in plant pathogenicity. Growth of the
      Deltatps1 mutant was more heat sensitive compared to the wild-type. Similarly,
      Deltatps1 conidia showed a shorter survival under heat stress, and their
      viability at moderate temperatures was strongly reduced. In germinating wild-type
      conidia, rapid trehalose degradation occurred only when germination was induced
      in the presence of nutrients. In contrast, little trehalose breakdown was
      observed during germination on hydrophobic surfaces in water. Here, addition of
      cAMP to conidia induced trehalose mobilization and accelerated the germination
      process, probably by activation of TRE1. In accordance with these data, both
      mutants showed germination defects only in the presence of sugars but not on
      hydrophobic surfaces in the absence of nutrients. The data indicate that in B.
      cinerea trehalose serves as a stress protectant, and also as a significant but
      not essential carbon source for germination when external nutrients are low. In
      addition, evidence was obtained that trehalose 6-phosphate plays a role as a
      regulator of glycolysis during germination.

PMID- 16946259
TI  - KlRHO1 and KlPKC1 are essential for cell integrity signalling in Kluyveromyces
      lactis.
AB  - Cell integrity in yeasts is ensured by a rigid cell wall whose synthesis is
      triggered by a MAP kinase-mediated signal-transduction cascade. Upstream
      regulatory components of this pathway in Saccharomyces cerevisiae involve a
      single protein kinase C, which is regulated by interaction with the small GTPase
      Rho1. Here, two genes were isolated which encode these proteins from
      Kluyveromyces lactis (KlPKC1 and KlRHO1). Sequencing showed ORFs which encode
      proteins of 1,161 and 208 amino acids, respectively. The deduced proteins shared
      59 and 85 % overall amino acid identities, respectively, with their homologues
      from S. cerevisiae. Null mutants in both genes were non-viable, as shown by
      tetrad analyses of the heterozygous diploid strains. Overexpression of the KlRHO1
      gene under the control of the ScGAL1 promoter severely impaired growth in both S.
      cerevisiae and K. lactis. On the other hand, a similar construct with KlPKC1 did
      not show a pronounced phenotype. Two-hybrid analyses showed interaction between
      Rho1 and Pkc1 for the K. lactis proteins and their S. cerevisiae homologues. A
      green fluorescent protein (GFP) fusion to the C-terminal end of KlPkc1 located
      the protein to patches in the growing bud, and at certain stages of the division
      process also to the bud neck. N-terminal GFP fusions to KlRho1 localized mainly
      to the cell surface (presumably the cytoplasmic side of the plasma membrane) and
      to the vacuole, with some indications of traffic from the former to the latter.
      Thus, KlPkc1 and KlRho1 have been shown to serve vital functions in K. lactis, to
      interact in cell integrity signalling and to traffic between the plasma membrane
      and the vacuole.

PMID- 16946260
TI  - Cyt1Ca from Bacillus thuringiensis subsp. israelensis: production in Escherichia
      coli and comparison of its biological activities with those of other Cyt-like
      proteins.
AB  - The larvicidal activity of Bacillus thuringiensis subsp. israelensis against
      dipteran larvae is determined by four major polypeptides of the parasporal
      crystalline body produced during sporulation. Cyt1Aa shows the lowest toxicity
      when used alone but is the most synergistic with any of the other proteins. The
      sequence of the plasmid pBtoxis, which contains all the toxin genes in this
      subspecies, revealed a new cyt-like coding sequence named cyt1Ca. In addition to
      the Cyt-like region, the predicted Cyt1Ca contained an extra domain at the C
      terminus, which appeared to be a beta-trefoil carbohydrate-binding motif, as
      found in several ricin-like toxins. The gene was PCR-amplified from pBtoxis and
      cloned in several vectors, allowing high-level expression in Escherichia coli.
      Cyt1Ca was purified by nickel-nitrilotriacetic acid affinity chromatography,
      characterized, and its biological activity was determined. Toxicity against
      larvae of Aedes aegypti of Cyt1Ca in recombinant E. coli cells was compared with
      that of Cyt1Aa and Cyt2Ba, and the ability of these proteins to enhance the
      activity of Cry4Aa was assessed. Although Cyt2Ba appeared able to interact with
      Cry4Aa, no activity for Cyt1Ca was observed, even when produced in truncated
      form. Furthermore, in contrast to Cyt1Aa, Cyt1Ca did not lyse sheep erythrocytes,
      and it was not bactericidal to the host cell.

PMID- 16946261
TI  - Regulation of class D beta-lactamase gene expression in Ralstonia pickettii.
AB  - Ralstonia pickettii, an environmental bacterium that may also be responsible for
      human infections, produces two unrelated, inducible and chromosomally encoded
      oxacillinases, OXA-22 and OXA-60. In order to study the molecular basis of the
      induction process of these oxacillinase genes, the induction kinetics, the
      promoter/operator regions necessary for expression and induction, and the role of
      several ORFs located upstream and downstream of the bla(OXA) genes were
      investigated. The beta-lactamase production reached a maximal level after 1 h
      induction, returned to its basal level within the following 3 h and was then
      again inducible. Using 5'RACE experiments, the promoter sequences of both
      oxacillinases were determined. These sequences showed weak promoter activities,
      which could, however, be increased approximately 200-fold by mutating the -35
      promoter sequence. Deletion of the sequences located upstream of the promoter
      regions did not modify the basal beta-lactamase expression in R. pickettii, but
      resulted in the lack of induction. A minimum of 240 and 270 bp upstream of the
      transcription initiation sites was required for inducible expression of the
      bla(OXA-22) and bla(OXA-60) genes, respectively. Analysis of the genetic
      environment of both bla(OXA) genes revealed several ORFs that were inactivated by
      homologous recombination. Disruption of ORF-RP3, located 190 bp upstream of
      bla(OXA-60) and divergently transcribed, abolished induction of both beta
      lactamases. ORF-RP3, which encoded a polypeptide of 532 aa with an estimated
      molecular mass of 58.7 kDa, displayed no obvious sequence homology with known
      regulatory proteins. Trans-complementation of ORF-RP3 restored the basal and
      inducible expression of both oxacillinase genes, indicating that the induction of
      both enzymes was related to the presence of ORF-RP3. In addition to the loss of
      induction, inactivation of the ORF-RP3 in R. pickettii resulted in a complex
      pleiotropic phenotype, with increased lag phase and reduced survival after heat
      exposure, suggesting that ORF-RP3 might be a global regulator involved in
      unrelated regulatory pathways.

PMID- 16946262
TI  - Bacterial factors influencing adhesion of Pseudomonas aeruginosa strains to a
      poly(ethylene oxide) brush.
AB  - Most bacterial strains adhere poorly to poly(ethylene oxide) (PEO)-brush
      coatings, with the exception of a Pseudomonas aeruginosa strain. The aim of this
      study was to find factors determining whether P. aeruginosa strains do or do not
      adhere to a PEO-brush coating in a parallel plate flow chamber. On the basis of
      their adhesion, a distinction could be made between three adhesive and three non
      adhesive strains of P. aeruginosa, while bacterial motilities and zeta potentials
      were comparable for all six strains. However, water contact angles indicated that
      the adhesive strains were much more hydrophobic than the non-adhesive strains.
      Furthermore, only adhesive strains released surfactive extracellular substances,
      which may be engaged in attractive interactions with the PEO chains. Atomic force
      microscopy showed that the adhesion energy, measured from the retract curves of a
      bacterial-coated cantilever from a brush coating, was significantly more negative
      for adhesive strains than for non-adhesive strains (P<0.001). Through surface
      thermodynamic and extended-DLVO (Derjaguin, Landau, Verwey, Overbeek) analyses,
      these stronger adhesion energies could be attributed to acid-base interactions.
      However, the energies of adhesion of all strains to a brush coating were small
      when compared with their energies of adhesion to a glass surface. Accordingly,
      even the adhesive P. aeruginosa strains could be easily removed from a PEO-brush
      coating by the passage of a liquid-air interface. In conclusion, cell surface
      hydrophobicity and surfactant release are the main factors involved in adhesion
      of P. aeruginosa strains to PEO-brush coatings.

PMID- 16946263
TI  - DNA secretion and gene-level selection in bacteria.
AB  - Natural genetic transformation can facilitate gene transfer in many genera of
      bacteria and requires the presence of extracellular DNA. Although cell lysis can
      contribute to this extracellular DNA pool, several studies have suggested that
      the secretion of DNA from living bacteria may also provide genetic material for
      transformation. This paper reviews the evidence for specific secretion of DNA
      from intact bacteria into the extracellular environment and examines this
      behaviour from a population-genetics perspective. A mathematical model
      demonstrates that the joint action of DNA secretion and transformation creates a
      novel type of gene-level natural selection. This model demonstrates that gene
      level selection could explain the existence of DNA secretion mechanisms that
      provide no benefit to individual cells or populations of bacteria. Additionally,
      the model predicts that any trait affecting DNA secretion will experience
      selection at the gene level in a transforming population. This analysis confirms
      that the secretion of DNA from intact bacterial cells is fully explicable with
      evolutionary theory, and reveals a novel mechanism for bacterial evolution.

PMID- 16946265
TI  - Plasmid pSci6 from Spiroplasma citri GII-3 confers insect transmissibility to the
      non-transmissible strain S. citri 44.
AB  - The insect-transmissible strain GII-3 of Spiroplasma citri contains plasmids
      pSci1-6, five of which (pSci1-5) encode adhesin-like proteins and one (pSci6)
      encodes protein P32, which has been associated with insect transmissibility. In
      contrast, S. citri strains ASP-1 and 44, which cannot be transmitted via
      injection into the leafhopper vector Circulifer haematoceps, lack these proteins
      and also do not carry plasmids pSci1-6. To further study the apparent
      relationship between the presence of plasmids and insect transmissibility,
      plasmids from S. citri GII-3 were introduced into the insect-non-transmissible S.
      citri strain 44 by electrotransformation using the tetM gene as the selection
      marker. Tetracycline-resistant transformants were shown to carry one, two or
      three distinct plasmids. Plasmids pSci1-6 were all detected in the transformants,
      pSci1 being the most frequently found, alone or together with other plasmids.
      Selected S. citri 44 transformants having distinct plasmid contents were
      submitted, separately or in combination, to experimental transmission to
      periwinkle (Catharanthus roseus) plants via injection into the leafhopper vector.
      The occurrence of symptomatic plants indicated that, in contrast to S. citri 44,
      spiroplasmal transformants were transmitted to the host plant, in which they
      multiplied. Spiroplasma cultures isolated from these infected plants all
      contained pSci6, leading to the conclusion that, under the experimental
      conditions used, transformation by pSci6 conferred insect transmissibility to S.
      citri strain 44. This is believed to be the first report of a phenotypic change
      associated with transformation of S. citri by natural plasmids.

PMID- 16946264
TI  - Plasmids from freshwater environments capable of IncQ retrotransfer are diverse
      and include pQKH54, a new IncP-1 subgroup archetype.
AB  - Nine mercury-resistance plasmids isolated from river epilithon were assessed for
      their ability to retrotransfer the non-conjugative IncQ plasmid, R300B,
      derivatives of which have commercial uses that may result in accidental or
      deliberate release into the environment. Retrotransfer frequencies ranging from
      2.1 x 10(-4) to 1.75 x 10(-5) were obtained for five of the nine plasmids--the
      remaining plasmids showed low or undetectable retrotransfer ability. The majority
      of the retrotransfer-proficient plasmids could not be classified by the tests
      used. Classical incompatibility testing with RP4 identified pQKH6, pQKH54 and
      pQM719 as IncP-1. Hybridization to replicon probes confirmed this for pQKH6 and
      pQM719 and added pQKH33. PCR with primers designed to amplify trfA and korA
      regions of IncP-1 plasmids did not identify any other plasmids. Plasmids pQKH6
      and pQM719 but not pQKH54 produced similar SphI restriction profiles to the IncP
      1beta subgroup. The complete nucleotide sequence of pQKH54 was determined,
      revealing it to have a complete IncP-1 backbone but belonging to a new distinct
      subgroup which was designated IncP-1gamma. The results emphasize the ubiquity and
      diversity of IncP-1 plasmids in the environment but demonstrate that plasmids of
      as yet unknown groups are also able to retrotransfer IncQ plasmids efficiently.

PMID- 16946266
TI  - Identification of a diacylglycerol acyltransferase gene involved in accumulation
      of triacylglycerol in Mycobacterium tuberculosis under stress.
AB  - Mycobacterium tuberculosis under stress stores triacylglycerol (TG). There are 15
      genes in M. tuberculosis that belong to a novel family of TG synthase genes
      (tgs), but it is not known which of them is responsible for this accumulation of
      TG. In this paper, it is reported that M. tuberculosis H37Rv accumulated TG under
      acidic, static or hypoxic growth conditions, or upon treatment with NO, whereas
      TG accumulation was drastically reduced in the tgs1 (Rv3130c) disrupted mutant.
      Complementation with tgs1 restored this TG accumulation. C(26) was a major fatty
      acid in this TG, indicating that the TGS1 gene product uses C(26) fatty acid,
      which is known to be produced by the mycobacterial fatty acid synthase. TGS1
      expressed in Escherichia coli preferred C(26 : 0)-CoA for TG synthesis. If TG
      storage is needed for the long-term survival of M. tuberculosis under dormant
      conditions, the tgs1 product could be a suitable target for antilatency drugs.

PMID- 16946267
TI  - Identification of the Mycobacterium tuberculosis GlnE promoter and its response
      to nitrogen availability.
AB  - Adenylyltransferase, GlnE, has a predicted role in controlling the enzymic
      activity of glutamine synthetase, the key enzyme in ammonia assimilation. It was
      previously demonstrated that glnE is an essential gene in Mycobacterium
      tuberculosis. glnE is located downstream of glnA2, one of four glutamine
      synthetases. The expression of GlnE under various conditions was determined.
      Although a co-transcript of glnA2 and glnE was detectable, the major transcript
      was monocistronic. A transcriptional start site immediately upstream of glnE was
      identified and it was shown by site-directed mutagenesis that the predicted -10
      region is a functional promoter. It was demonstrated that in a Mycobacterium
      smegmatis background M. tuberculosis P(glnE) was up-regulated in ammonia- or
      glutamine-containing media.

PMID- 16946268
TI  - Mycobacterium smegmatis whmD and its homologue Mycobacterium tuberculosis whiB2
      are functionally equivalent.
AB  - Mycobacterium smegmatis whmD is is an essential gene involved in cell division.
      This paper shows that whmD and its homologue whiB2 in Mycobacterium tuberculosis
      are functionally equivalent. The genes are syntenous, and share significant
      homology in both their coding and non-coding DNA sequences. Transcription site
      mapping showed that the two genes possess near-identical promoter elements, and
      they displayed comparable promoter strengths in a reporter gene assay. The two
      proteins show near identity in their C-terminus, and polyclonal antiserum to WhmD
      specifically cross-reacts with a approximately 15 kDa band in M. tuberculosis
      lysates. Following overexpression of sense and anti-sense constructs in their
      cognate mycobacterial hosts, whiB2 and whmD transformants displayed a small
      colony phenotype, exhibited filamentation, and showed a reduction in viability.
      These observations reveal that the two proteins are functionally homologous and
      that their intracellular concentration is critical for septation in mycobacteria.
      Colonies of M. tuberculosis overexpressing whiB2 were spherical and glossy,
      suggesting a change in composition of the cell envelope. Filaments of the
      conditionally complemented M. smegmatis whmD mutant were non-acid-fast, also
      indicating changes in characteristics of surface lipids. M. smegmatis
      transformants carrying a whmD-gfp fusion showed a diffuse pattern of
      fluorescence, consistent with the putative role of WhmD as a regulator. These
      observations strongly suggest that M. tuberculosis whiB2 is an essential gene and
      its protein product in all likelihood regulates the expression of genes involved
      in the cell division cascade.

PMID- 16946269
TI  - Regulation of the expression of whiB1 in Mycobacterium tuberculosis: role of cAMP
      receptor protein.
AB  - The wbl (whiB-like) genes encode putative transcription factors unique to
      actinomycetes. This study characterized the promoter element of one of the seven
      wbl genes of Mycobacterium tuberculosis, whiB1 (Rv3219c). The results reveal that
      whiB1 is transcribed by a class I-type cAMP receptor protein (CRP)-dependent
      promoter, harbouring a CRP-binding site positioned at -58.5 with respect to its
      transcription start point. In vivo promoter activity analysis and electrophoretic
      mobility shift assays suggest that the expression of whiB1 is indeed regulated by
      cAMP-dependent binding of CRP(M) (encoded by the M. tuberculosis gene Rv3676) to
      the whiB1 5' untranslated region (5'UTR). beta-Galactosidase gene fusion analysis
      revealed induction of the whiB1 promoter in M. tuberculosis on addition of
      exogenous dibutyric cAMP (a diffusible cAMP analogue) only when an intact CRP
      binding site was present. These results indicate that M. tuberculosis whiB1
      transcription is regulated in part by cAMP levels via direct binding of cAMP
      activated CRP(M) to a consensus CRP-binding site in the whiB1 5'UTR.

PMID- 16946270
TI  - Metabolic fingerprints of Mycobacterium bovis cluster with molecular type:
      implications for genotype-phenotype links.
AB  - Mycobacterium bovis is the causative agent of bovine tuberculosis. Various
      genetic typing techniques have been used to trace the reservoirs of infection;
      however, they have limited success in population genetics and outbreak studies.
      Fourier-transform infrared spectroscopy (FT-IR) is a rapid phenotypic typing
      technique, which may be used to generate a metabolic fingerprinting and is
      increasingly used to characterize bacteria. When coupled with multivariate
      cluster analysis, this powerful combination has sufficient resolving power to
      discriminate bacteria down to subspecies level; however, to date this method has
      not been used in the differentiation of mycobacteria. Multiple isolates of the
      ten major spoligotypes in the UK, recovered from different geographical
      locations, were analysed using FT-IR. Hierarchical cluster analysis of the
      spectra showed that the isolates could be differentiated according to their
      spoligotypes. Six of the spoligotype FT-IR clusters were very homogeneous and all
      isolates were recovered together. However, the remaining four groups displayed a
      more heterogeneous phenotype, which may reflect greater variation than previously
      suspected within these groups. Included in the ten spoligotypes are the two most
      dominant isolates in the UK, designated types 9 and 17. Whilst type 17 showed a
      highly conserved phenotype as judged by FT-IR, type 9 showed a very heterogeneous
      metabolic profile and isolates were recovered throughout the dendrogram. This
      variation in type 9 is reflected in the high degree of diversity observed by
      variable number tandem repeats (VNTR) analysis, underlining the exquisite
      resolving power of FT-IR.

PMID- 16946271
TI  - Anaerobic and aerobic metabolism of glycogen-accumulating organisms selected with
      propionate as the sole carbon source.
AB  - In the microbial competition observed in enhanced biological phosphorus removal
      (EBPR) systems, an undesirable group of micro-organisms known as glycogen
      accumulating organisms (GAOs) compete for carbon in the anaerobic period with the
      desired polyphosphate-accumulating organisms (PAOs). Some studies have suggested
      that a propionate carbon source provides PAOs with a competitive advantage over
      GAOs in EBPR systems; however, the metabolism of GAOs with this carbon source has
      not been previously investigated. In this study, GAOs were enriched in a
      laboratory-scale bioreactor with propionate as the sole carbon source, in an
      effort to better understand their biochemical processes. Based on comprehensive
      solid-, liquid- and gas-phase chemical analytical data from the bioreactor, a
      metabolic model was proposed for the metabolism of propionate by GAOs. The model
      adequately described the anaerobic stoichiometry observed through chemical
      analysis, and can be a valuable tool for further investigation of the competition
      between PAOs and GAOs, and for the optimization of the EBPR process. A group of
      Alphaproteobacteria dominated the biomass (96 % of Bacteria) from this
      bioreactor, while post-fluorescence in situ hybridization (FISH) chemical
      staining confirmed that these Alphaproteobacteria produced poly-beta
      hydroxyalkanoates (PHAs) anaerobically and utilized them aerobically,
      demonstrating that they were putative GAOs. Some of the Alphaproteobacteria were
      related to Defluvicoccus vanus (16 % of Bacteria), but the specific identity of
      many could not be determined by FISH. Further investigation into the identity of
      other GAOs is necessary.

PMID- 16946272
TI  - Involvement of the S-layer proteins Hpi and SlpA in the maintenance of cell
      envelope integrity in Deinococcus radiodurans R1.
AB  - The potential functions have been investigated of two proteins in Deinococcus
      radiodurans R1 predicted to be involved in the maintenance and integrity of the S
      layer: the hexagonally packed intermediate (Hpi) protein, and SlpA (DR2577), a
      homologue of an S-layer SlpA protein in Thermus thermophilus. Deletion of the hpi
      gene had little effect on the structure of the cell envelope or on shear- or
      solvent-induced stress responses. However, deletion of the slpA gene caused
      substantial alterations in cell envelope structure, and a significant defect in
      resistance to solvent and shear stresses compared to the wild-type.
      Ultrastructural analysis of slpA mutant cells indicated loss of much of the outer
      Hpi protein carbohydrate coat, the 'pink envelope', and the membrane-like backing
      layer. Together these results suggest that the SlpA protein may be involved in
      attachment of the Hpi surface layer to the inner cell envelope, and that SlpA may
      play an important role in the maintenance of cell envelope integrity in D.
      radiodurans.

PMID- 16946273
TI  - Laboratory and clinical Pseudomonas aeruginosa strains do not bind
      glycosphingolipids in vitro or during type IV pili-mediated initial host cell
      attachment.
AB  - The glycosphingolipids (GSLs) gangliotriaosylceramide (Gg(3)) and
      gangliotetraosylceramide (Gg(4)) have been implicated as receptors for type IV
      pili (T4P)-mediated Pseudomonas aeruginosa epithelial cell attachment. Since P.
      aeruginosa T4P are divided into five groups, the authors determined whether GSLs
      in general, and Gg(3) and Gg(4) in particular, are specifically bound and
      required for host epithelial cell attachment of clinical and laboratory strains
      within these groups. An enterohaemorrhagic Escherichia coli strain, CL56, known
      to bind to both Gg(3) and Gg(4), provided a positive control. TLC overlay showed
      no binding of more than 12 P. aeruginosa strains to either Gg(3) or Gg(4) (or
      other GSLs), while CL56 Gg(3)/Gg(4) binding was readily detectable. GSL ELISA
      similarly demonstrated no significant P. aeruginosa binding to Gg(3) or Gg(4),
      compared with CL56. Using a selective chemical inhibitor, epithelial cell GSL
      synthesis was abrogated, and Gg(3) and Gg(4) expression deleted, but P.
      aeruginosa attachment was not impaired. Target cell attachment was mediated by
      T4P, since non-piliated, but flagellated, mutants were unable to bind to the
      target cells. CFTR (cystic fibrosis transmembrane conductance regulator) has also
      been implicated as a receptor; however, in this work, overexpression of CFTR had
      no effect on P. aeruginosa binding. It is concluded that neither Gg(3) nor Gg(4)
      are specifically recognized by P. aeruginosa, and that endogenous GSLs do not
      have a role in the attachment of live intact P. aeruginosa to cultured lung
      epithelial cells. In contrast to whole piliated P. aeruginosa, T4P sheared from
      such bacteria showed significant Gg(3) and Gg(4) binding, which may explain the
      results of other studies.

PMID- 16946274
TI  - Biofilm formation by a Bacillus subtilis strain that produces gamma
      polyglutamate.
AB  - The extracellular matrix produced by Bacillus subtilis B-1, an environmental
      strain that forms robust floating biofilms, was purified, and determined to be
      composed predominantly of gamma-polyglutamate (gamma-PGA), with a molecular mass
      of over 1,000 kDa. Both biofilm formation and gamma-PGA production by B. subtilis
      B-1 increased with increasing Mn(2+) or glycerol concentration. gamma-PGA was
      produced in a growth-associated manner in standing culture, and floating biofilms
      were formed. However, gamma-PGA was produced in a non-growth-associated manner in
      shaking culture conditions. When B. subtilis B-1 was grown in a microaerated
      culture system, floating biofilm formation and gamma-PGA production were
      significantly retarded, suggesting that oxygen depletion is involved in the
      initial steps of floating biofilm formation in standing culture. Proteomic
      analysis of membrane proteins demonstrated that flagellin, oligopeptide permease
      and Vpr protease precursor were the major proteins produced by cells in a
      floating biofilm and a colony.

PMID- 16946275
TI  - AopP, a type III effector protein of Aeromonas salmonicida, inhibits the NF
      kappaB signalling pathway.
AB  - Aeromonas salmonicida subsp. salmonicida contains a functional type III secretion
      system that is responsible for the secretion of the ADP-ribosylating toxin AexT.
      In this study, the authors identified AopP as a second effector protein secreted
      by this system. The aopP gene was detected in both typical and atypical A.
      salmonicida isolates and was found to be encoded on a small plasmid of
      approximately 6.4 kb. Sequence analysis indicates that AopP is a member of the
      YopJ family of effector proteins, a group of proteins that interfere with mitogen
      activated protein kinase (MAPK) and/or nuclear factor kappa B (NF-kappaB)
      signalling pathways. AopP inhibits the NF-kappaB pathway downstream of IkappaB
      kinase (IKK) activation, while a catalytically inactivated mutant, AopPC177A,
      does not possess this inhibitory effect. Unlike other effectors of the YopJ
      family, such as YopJ and VopA, AopP does not inhibit the MAPK signalling pathway.

PMID- 16946276
TI  - Mechanisms of copper loading on the Schizosaccharomyces pombe copper amine
      oxidase 1 expressed in Saccharomyces cerevisiae.
AB  - Copper amine oxidases (CAOs) are found in almost every living kingdom. Although
      Saccharomyces cerevisiae is one of the few yeast species that lacks an endogenous
      CAO, heterologous gene expression of CAOs from other organisms produces a
      functional enzyme. To begin to characterize their function and mechanisms of
      copper acquisition, two putative cao(+) genes from Schizosaccharomyces pombe were
      expressed in S. cerevisiae. Expression of spao1(+) resulted in the production of
      an active enzyme capable of catalysing the oxidative deamination of primary
      amines. On the other hand, expression of spao2(+) failed to produce an active
      CAO. Using a functional spao1(+)-GFP fusion allele, the SPAO1 protein was
      localized in the cytosol. Under copper-limiting conditions, yeast cells
      harbouring deletions of the MAC1, CTR1 and CTR3 genes were defective in amine
      oxidase activity. Likewise, atx1Delta null cells exhibited no CAO activity, while
      ccc2Delta mutant cells exhibited decreased levels of amine oxidase activity, and
      mutations in cox17Delta and ccs1Delta did not cause any defects in this activity.
      Copper-deprived S. cerevisiae cells expressing spao1(+) required a functional
      atx1(+) gene for growth on minimal medium containing ethylamine as the sole
      nitrogen source. Under these conditions, the inability of the atx1Delta cells to
      utilize ethylamine correlated with the lack of SPAO1 activity, in spite of the
      efficient expression of the protein. Cells carrying a disrupted ccc2Delta allele
      exhibited only weak growth on ethylamine medium containing a copper chelator. The
      results of these studies reveal that expression of the heterologous spao1(+) gene
      in S. cerevisiae is required for its growth in medium containing ethylamine as
      the sole nitrogen source, and that expression of an active Schiz. pombe SPAO1
      protein in S. cerevisiae depends on the acquisition of copper through the high
      affinity copper transporters Ctr1 and Ctr3, and the copper chaperone Atx1.

PMID- 16946278
TI  - EST analysis of cDNA libraries from the entomopathogenic fungus Beauveria
      (Cordyceps) bassiana. I. Evidence for stage-specific gene expression in aerial
      conidia, in vitro blastospores and submerged conidia.
AB  - The entomopathogenic fungus Beauveria (Cordyceps) bassiana holds much promise as
      a pest biological control agent. B. bassiana produces at least three in vitro
      single cell infectious propagules, including aerial conidia, vegetative cells
      termed blastospores and submerged conidia, that display different morphological,
      biochemical and virulence properties. Populations of aerial conidia, blastospores
      and submerged conidia were produced on agar plates, rich liquid broth cultures
      and under conditions of nutrient limitation in submerged cultures, respectively.
      cDNA libraries were generated from mRNA isolated from each B. bassiana cell type
      and approximately 2,500 5' end sequences were determined from each library.
      Sequences derived from aerial conidia clustered into 284 contigs and 963
      singlets, with those derived from blastospores and submerged conidia forming 327
      contigs with 788 singlets, and 303 contigs and 1,079 contigs, respectively.
      Almost half (40-45 %) of the sequences in each library displayed either no
      significant similarity (e value >10(-4)) or similarity to hypothetical proteins
      found in the NCBI database. The expressed sequence tag dataset also included
      sequences representing a significant portion of proteins in cellular metabolism,
      information storage and processing, transport and cell processes, including cell
      division and posttranslational modifications. Transcripts encoding a diverse
      array of pathogenicity-related genes, including proteases, lipases, esterases,
      phosphatases and enzymes producing toxic secondary metabolites, were also
      identified. Comparative analysis between the libraries identified 2,416 unique
      sequences, of which 20-30 % were unique to each library, and only approximately 6
      % of the sequences were shared between all three libraries. The unique and
      divergent representation of the B. bassiana transcriptome in the cDNA libraries
      from each cell type suggests robust differential gene expression profiles in
      response to environmental conditions.

PMID- 16946277
TI  - In vivo monitoring of the potassium channel KcsA in Streptomyces lividans hyphae
      using immuno-electron microscopy and energy-filtering transmission electron
      microscopy.
AB  - The previous discovery of the Streptomyces lividans kcsA gene and its
      overexpression followed by the functional reconstitution of the purified gene
      product has resulted in new strategies to explore this channel protein in vitro.
      KcsA has evolved as a general model to investigate the structure/function
      relationship of ion channel proteins. Using specific antibodies raised against a
      domain of KcsA lacking membrane-spanning regions, KcsA has now been localized
      within numerous separated clusters between the outer face of the cytoplasm and
      the cell envelope in substrate hyphae of the S. lividans wild-type strain but not
      in a designed chromosomal disruption mutant DeltaK, lacking a functional kcsA
      gene. Previous findings had revealed that caesium ions led to a block of KcsA
      channel activity within S. lividans protoplasts fused to giant vesicles. As
      caesium can be scored by electron energy loss spectroscopy better than potassium,
      this technique was applied to hyphae that had been briefly exposed to caesium
      instead of potassium ions. Caesium was found preferentially at the cell envelope.
      Compared to the DeltaK mutant, the relative level of caesium was approximately 30
      % enhanced in the wild-type. This is attributed to the presence of KcsA channels.
      Additional visualization by electron spectroscopic imaging supported this
      conclusion. The data presented are believed to represent the first demonstration
      of in vivo monitoring of KcsA in its original host.

PMID- 16946279
TI  - EST analysis of cDNA libraries from the entomopathogenic fungus Beauveria
      (Cordyceps) bassiana. II. Fungal cells sporulating on chitin and producing
      oosporein.
AB  - In the accompanying paper [Cho, E.-M., Liu, L., Farmerie, W. & Keyhani, N. O.
      (2006). Microbiology 152, 2843-2854], the analysis of expressed sequence tag
      (EST) libraries derived from homogeneous single-cell populations of aerial
      conidia, in vitro blastospores and submerged conidia of the entomopathogenic
      fungus Beauveria (Cordyceps) bassiana has been reported. Here an extended EST
      analysis is presented of complex cell mixtures derived from fungal cells
      sporulating on chitin or grown under culture conditions inducing the production
      of the B. bassiana secondary metabolite, oosporein. Fungal material used for the
      construction of the libraries included germinating conidia and blastospores,
      mycelia, as well as cells in various developmental stages. Approximately 2,500 5'
      end sequences were determined from random sequencing of clones from each library,
      and were clustered into 277 contigs with 1,069 singlets, and 306 contigs with
      1,064 singlets, for the chitin and oosporein libraries, respectively. Almost half
      (45-50 %) of the sequences in each library displayed either no significant
      similarity (e value >10(-4)) or similarity to hypothetical proteins found in the
      NCBI database. Approximately 20-25 % of the sequences in each library could be
      annotated by gene ontology terms. A comparative analysis between the two
      libraries, as well as the libraries in the accompanying paper, is presented. A
      set of 4,360 clustered and unique sequences was characterized. The data are
      indicative of a highly plastic gene expression repertoire being available to B.
      bassiana for growth during different environmental and developmental conditions,
      and provides a dataset for gene discovery and genome annotation.

PMID- 16946280
TI  - Procedural sedation in the community emergency department: initial results of the
      ProSCED registry.
AB  - OBJECTIVES: Procedural sedation and analgesia (PSA) has been well profiled in
      experimental studies in university emergency departments. Extrapolation of these
      practices into the community hospital setting is not well established. This
      report describes community hospital practices and outcomes in a multicenter PSA
      registry. METHODS: The Procedural Sedation in the Community Emergency Department
      (ProSCED) registry is a prospective observational database composed of
      consecutive emergency physician-directed procedural sedation cases in community
      hospitals. Registered procedures described by 15 categorical data fields are
      collected at the time of the patient encounter and entered into a secure Internet
      housed database. RESULTS: A total of 1,028 procedural sedations were performed on
      980 patients at 14 study sites. The most common specified procedures performed
      included shoulder relocation (392), hip relocation (102), elbow relocation (70),
      upper extremity fracture care (69), lower extremity fracture care (66), and
      facial laceration repair (67). Complications of any description occurred in 42
      cases (4.1%), with no patient's disposition changed secondary to a complication.
      Patients' ages ranged from 1 month to 95 years, with a median age of 31 years. Of
      procedures attempted, 982 (95.5%) were successfully completed, 21 cases (2.0%)
      were adequately sedated but unable to have their procedure completed, and 21
      cases (2.0%) were believed to be inadequately sedated. Medication use included
      midazolam in 423 cases (41.1%), propofol in 253 (24.6%), fentanyl in 253 (24.6%),
      etomidate in 241 (23.4%), and ketamine in 145 (14.1%), as well as several others.
      Cases using either ketamine or propofol exhibited the fewest complications, while
      those using fentanyl, hydromorphone, or midazolam demonstrated the highest
      complication rates. CONCLUSIONS: Community emergency physicians deliver safe and
      effective PSA over a wide variety of ages and procedures while using a broad
      selection of agents.

PMID- 16946281
TI  - The effects of ambulance diversion: a comprehensive review.
AB  - OBJECTIVES: To review the current literature on the effects of ambulance
      diversion (AD). METHODS: The authors performed a systematic review of AD and its
      effects. PubMed, EMBASE, the Cochrane database, societal meeting abstracts, and
      references from relevant articles were searched. All articles were screened for
      relevance to AD. RESULTS: The authors examined 600 citations and reviewed the 107
      articles relevant to AD. AD is a common occurrence that is increasing in
      frequency. AD is associated with periods of emergency department (ED) crowding
      (Mondays, mid-afternoon to early evening, influenza season, and when hospitals
      are at capacity). Interventions that redesign the AD process or that provide
      additional hospital or ED resources reduce diversion frequency. AD is associated
      with increased patient transport times and time to thrombolytics but not with
      mortality. AD is associated with loss of estimated hospital revenues. Short of
      anecdotal or case reports, no studies measured the effect of AD on ED crowding,
      morbidity, patient and provider satisfaction, or EMS resource utilization.
      CONCLUSIONS: Despite its common use, there is a relative paucity of studies on
      the effects of AD. Further research into these effects should be performed so
      that we may understand the role of AD in the health system.

PMID- 16946282
TI  - Evaluating "ED STAT!": a novel and effective faculty development program to
      improve emergency department teaching.
AB  - OBJECTIVES: Effective clinical teaching in emergency departments (EDs) presents
      unique challenges. No validated approaches to enhancing ED teaching have been
      reported. The authors evaluated the effectiveness of a novel one-day evidence
      based, skills-oriented faculty development course tailored to ED teachers (ED
      STAT!). METHODS: The authors invited all inaugural course registrants to
      participate in this program evaluation study. The authors assessed participants'
      knowledge change and perceived change in teaching behavior using a multiple
      choice and short-answer question examination, a teaching behaviors questionnaire,
      and a survey for satisfaction. Data were gathered before, immediately after, and
      one month after the course. Mean scores were compared using the Wilcoxon signed
      rank test, and qualitative results were analyzed via a grounded theory approach.
      RESULTS: Thirty-one individuals from a variety of academic and community EDs
      completed the May 2005 course; 28 participated in the pre-evaluation and
      postevaluation, and 22 participated in the one-month postevaluation. Multiple
      choice scores increased from pre-evaluation to one-month postcourse by 15.1% (p <
      0.001, effect size large: d = 1.53). Short-answer scores increased by 17.2% (p =
      0.001, effect size large: d = 0.90). After one month, 55% of participants
      reported an increased amount of teaching, 86% perceived this teaching to be of a
      greater quality, and 82% had shared new strategies with colleagues. The course
      would be recommended to a colleague by 96.3% of respondents. CONCLUSIONS: ED
      STAT! improves participants' knowledge about ED-specific teaching strategies, and
      this improvement is maintained at one month. Participants reported high
      satisfaction and a positive effect on teaching behavior.

PMID- 16946283
TI  - Emergency department performance measures and benchmarking summit.
AB  - The findings are presented of a consensus group created to address the
      standardization of performance measures for emergency medicine. This group, whose
      members have affiliations with most major organizations interested in emergency
      medicine performance, benchmarking and quality improvement, was tasked with
      standardizing definitions pertinent to emergency department performance measures,
      creating a set of general and operational measures, developing a comparison
      system for benchmarking and creating a plan for the dissemination of this
      information. The formation of this group, the problem statement, and the mission
      statement for the summit are all described, and the consensus document is
      presented.

PMID- 16946284
TI  - Adrenaline storm in the emergency physician.

PMID- 16946285
TI  - Care for the adult family members of victims of unexpected cardiac death.
AB  - More than 300,000 sudden coronary deaths occur annually in the United States,
      despite declining cardiovascular death rates. In 2000, deaths from heart disease
      left an estimated 190,156 new widows and 68,493 new widowers. A major unanswered
      question for emergency providers is whether the immediate care of the loved ones
      left behind by the deceased should be a therapeutic task for the staff of the
      emergency department in the aftermath of a fatal cardiac arrest. Based on a
      review of the literature, the authors suggest that more research is needed to
      answer this question, to assess the current immediate needs and care of
      survivors, and to find ways to improve care of the surviving family of unexpected
      cardiac death victims. This would include improving quality of death disclosure,
      improving care for relatives during cardiopulmonary resuscitation of their family
      member, and improved methods of referral for services for prevention of
      psychological and cardiovascular morbidity during bereavement.

PMID- 16946286
TI  - Ethics seminars: withdrawal of treatment in the emergency department--when and
      how?
AB  - Although increasing discussion has occurred within emergency medicine about
      indications for withholding cardiac life support and other resuscitative
      interventions, emergency physicians (EPs) may be less familiar with the ethical,
      legal, and practical issues surrounding withdrawal of life support that has
      already been initiated. Both physicians and out-of-hospital personnel must act
      rapidly in critical situations and must assume that the patient has the desire to
      be resuscitated, unless clear evidence exists to the contrary. Often, only after
      initial life-saving actions have stabilized the patient is there time to reflect
      and determine a patient's desires regarding such interventions. When the EP can
      clearly discern a patient's previously stated wishes during the emergency
      department (ED) stay, these wishes should be honored in the ED. Respecting a
      patient's request to avoid unwanted, invasive treatments near death may involve
      withdrawing interventions that could not be withheld during the first few minutes
      of care. In this article, the authors use a case of out-of-hospital stabilization
      of a patient as a springboard to review the ethical and legal framework for
      withdrawal of life-sustaining care, as well as the practical issues involved with
      withdrawal of such care in the ED.

PMID- 16946287
TI  - Limited opportunities for paramedic student endotracheal intubation training in
      the operating room.
AB  - BACKGROUND: Paramedics, who often are the first to provide emergency care to
      critically ill patients, must be proficient in endotracheal intubation (ETI).
      Training in the controlled operating room (OR) setting is a common method for
      learning basic ETI technique. OBJECTIVES: To determine the quantity and nature of
      OR ETI training currently provided to paramedic students. METHODS: The authors
      surveyed directors of paramedic training programs accredited by the Commission on
      Accreditation of Allied Health Education Programs. An anonymous 12-question,
      structured, closed-response survey instrument was used that requested information
      regarding the duration and nature of OR training provided to paramedic students.
      The results were analyzed by using descriptive statistics. RESULTS: From 192
      programs, 161 completed surveys were received (response rate, 85%). OR training
      was used at 156 programs (97%) but generally was limited (median, 17-32 hours per
      student). Half of the programs provided fewer than 16 OR hours per student.
      Students attempted a limited number of OR ETI (median, 6-10 ETI). Most
      respondents (61%) reported competition from other health care students for OR
      ETI. Other identified hindering factors included the increasing OR use of
      laryngeal mask airways and physicians' medicolegal concerns. Respondents from 52
      (33%) programs reported a recent reduction in OR access, and 56 (36%) programs
      expected future OR opportunities to decrease. CONCLUSIONS: Despite its key role
      in airway management education, the quantity and nature of OR ETI training that
      is available to paramedic students is limited in comparison to that available to
      other ETI providers.

PMID- 16946288
TI  - State of research in high-consequence hospital surge capacity.
AB  - High-consequence surge research involves a systems approach that includes
      elements such as healthcare facilities, out-of-hospital systems, mortuary
      services, public health, and sheltering. This article focuses on one aspect of
      this research, hospital surge capacity, and discusses a definition for such
      capacity, its components, and future considerations. While conceptual definitions
      of surge capacity exist, evidence-based practical guidelines for hospitals
      require enhancement. The Health Resources and Services Administration's (HRSA)
      definition and benchmarks are extrapolated from those of other countries and rely
      mainly on trauma data. The most significant part of the HRSA target, the need to
      care for 500 victims stricken with an infectious disease per one million
      population in 24 hours, was not developed using a biological model. If HRSA's
      recommendation is applied to a sample metropolitan area such as Orange County,
      California, this translates to a goal of expanding hospital capacity by 20%-25%
      in the first 24 hours. Literature supporting this target is largely consensus
      based or anecdotal. There are no current objective measures defining hospital
      surge capacity. The literature identifying the components of surge capacity is
      fairly consistent and lists them as personnel, supplies and equipment,
      facilities, and a management system. Studies identifying strategies for hospitals
      to enhance these components and estimates of how long it will take are lacking.
      One system for augmenting hospital staff, the Emergency System for Advance
      Registration of Volunteer Health Professionals, is a consensus-derived plan that
      has never been tested. Future challenges include developing strategies to handle
      the two different types of high-consequence surge events: 1) a focal, time
      limited event (such as an earthquake) where outside resources exist and can be
      mobilized to assist those in need and 2) a widespread, prolonged event (such as
      pandemic influenza) where all resources will be in use and rationing or triage is
      needed.

PMID- 16946289
TI  - Rewarming rates in urban patients with hypothermia: prediction of underlying
      infection.
AB  - BACKGROUND: In the urban setting, hypothermia is commonly associated with illness
      or intoxication, with death often secondary to infection. OBJECTIVES: To evaluate
      factors that affect the rewarming rate (RWR) and the ability of the RWR and other
      clinical markers to predict the presence or absence of underlying infection in an
      adult urban population. METHODS: This was a prospective observational study of
      hypothermic patient visits to a large emergency department. Serial temperatures
      were obtained during rewarming to construct rewarming curves. Rewarming
      modalities selected by emergency physicians were correlated with admission
      temperatures. Univariate associates of RWR and infection were assessed. RESULTS:
      The authors identified 96 patient visits. The median temperature was 89.5 degrees
      F (31.9 degrees C; range, 73.0 degrees F to 95.0 degrees F [22.8 degrees C to
      35.0 degrees C]). Thirteen patients had temperatures of < 80.0 degrees F (26.0
      degrees C). Seven died within 14 hours of presentation; six, of infection. No
      patient experienced ventricular fibrillation. Potential candidate predictors of
      infection from a multivariate analysis were a RWR of < 1.80 degrees F (1.0
      degrees C) per hour and a serum albumin of < 2.7 g/dL. Rapid rewarming was
      associated with the absence of infection and a temperature below 86.0 degrees F
      (30.0 degrees C). In patients without significant underlying illness, rewarming
      rates appeared to be independent of the modality of rewarming. CONCLUSIONS:
      Rewarming rates reflect intrinsic capacity for thermogenesis. Increased RWRs were
      associated with the absence of infection. The achievement of normothermia did not
      prevent death in infected patients. Initiation of invasive rewarming in urban
      patients with hypothermia who have not had hypothermic cardiac arrest may be
      unwarranted. Management of this population should emphasize support, detection,
      and treatment of underlying illness.

PMID- 16946290
TI  - Colles fracture reduction using ultrasound.

PMID- 16946291
TI  - Narrowing in on JCAHO recommendations for community-acquired pneumonia.

PMID- 16946292
TI  - Community pneumonia practice standard mandates: can't see the forest for the
      trees.

PMID- 16946293
TI  - Resident portfolio: a tale of two women.

PMID- 16946296
TI  - Comment on "endothelially derived nitric oxide affects the severity of early
      acetaminophen-induced hepatic injury in mice".

PMID- 16946298
TI  - STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation.
AB  - Hepcidin is a key iron-regulatory hormone produced by the liver. Inappropriately
      low hepcidin levels cause iron overload, while increased hepcidin expression
      plays an important role in the anemia of inflammation (AI) by restricting
      intestinal iron absorption and macrophage iron release. Its expression is
      modulated in response to body iron stores, hypoxia, and inflammatory and
      infectious stimuli involving at least in part cytokines secreted by macrophages.
      In this study we established and characterized IL6-mediated hepcidin activation
      in the human liver cell line Huh7. We show that the proximal 165 bp of the
      hepcidin promoter is critical for hepcidin activation in response to exogenously
      administered IL6 or to conditioned medium from the monocyte/macrophage cell line
      THP-1. Importantly, we show that hepcidin activation by these stimuli requires a
      STAT3 binding motif located at position -64/-72 of the promoter. The same STAT
      binding site is also required for high basal-level hepcidin mRNA expression under
      control culture conditions, and siRNA-mediated RNA knockdown of STAT3 strongly
      reduces hepcidin mRNA expression. These results identify a missing link in the
      acute-phase activation of hepcidin and establish STAT3 as a key effector of
      baseline hepcidin expression and during inflammatory conditions.

PMID- 16946299
TI  - CD200 is a new prognostic factor in multiple myeloma.
AB  - Using Affymetrix microarrays, we identified the expression of the CD200 gene in
      multiple myeloma cells (MMCs) of 112 patients with newly diagnosed multiple
      myeloma (MM). The CD200 gene was either absent or present (Affymetrix call) in
      22% and 78% of MMCs, respectively. The CD200 gene is not expressed in cells of
      the patients' bone marrow (BM). CD200 is a membrane glycoprotein that imparts an
      immunoregulatory signal through CD200R, leading to the suppression of T-cell
      mediated immune responses. Patients with CD200(absent) MMCs have an increased
      event-free survival (EFS; 24 months) compared with patients with CD200(present)
      MMCs (14 months), after high-dose therapy and stem cell transplantation. In a Cox
      proportional-hazard model, the absence or presence of CD200 expression in MMCs is
      predictive for EFS for patients independently of ISS stage or beta2M serum
      levels. Thus, CD200 is an independent prognosis factor for patients with MM that
      could represent a new therapeutic target in MM.

PMID- 16946300
TI  - Phosphotyrosine profiling identifies the KG-1 cell line as a model for the study
      of FGFR1 fusions in acute myeloid leukemia.
AB  - The 8p11 myeloproliferative syndrome (EMS) is associated with translocations that
      disrupt the FGFR1 gene. To date, 8 fusion partners of FGFR1 have been identified.
      However, no primary leukemia cell lines were identified that contain any of these
      fusions. Here, we screened more than 40 acute myeloid leukemia cell lines for
      constitutive phosphorylation of STAT5 and applied an immunoaffinity profiling
      strategy to identify tyrosine-phosphorylated proteins in the KG-1 cell line. Mass
      spectrometry analysis of KG-1 cells revealed aberrant tyrosine phosphorylation of
      FGFR1. Subsequent analysis led to the identification of a fusion of the FGFR1OP2
      gene to the FGFR1 gene. Small interfering RNA (siRNA) against FGFR1 specifically
      inhibited the growth and induced apoptosis of KG-1 cells. Thus, the KG-1 cell
      line provides an in vitro model for the study of FGFR1 fusions associated with
      leukemia and for the analysis of small molecule inhibitors against FGFR1 fusions.

PMID- 16946301
TI  - WHIM syndrome myelokathexis reproduced in the NOD/SCID mouse xenotransplant model
      engrafted with healthy human stem cells transduced with C-terminus-truncated
      CXCR4.
AB  - WHIM(warts, hypogammaglobulinemia, recurrent bacterial infection, and
      myelokathexis) syndrome is a rare immunodeficiency caused in many cases by
      autosomal dominant C-terminal truncation mutations in the chemokine receptor
      CXCR4. A prominent and unexplained feature of WHIM is myelokathexis
      (hypercellularity with apoptosis of mature myeloid cells in bone marrow and
      neutropenia). We transduced healthy human CD34(+) peripheral blood-mobilized stem
      cells (PBSCs) with retrovirus vector encoding wild-type (wt) CXCR4 or WHIM-type
      mutated CXCR4 and studied these cells ex vivo in culture and after engraftment in
      a nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse xenograft
      model. Neither wt CXCR4 nor mutated CXCR4 transgene expression itself enhanced
      apoptosis of neutrophils arising in transduced PBSC cultures even with
      stimulation by a CXCR4 agonist, stromal cell-derived factor-1 (SDF-1 [CXCL12]).
      Excess wt CXCR4 expression by transduced human PBSCs enhanced marrow engraftment,
      but did not affect bone marrow (BM) apoptosis or the release of transduced
      leukocytes into PB. However, mutated CXCR4 transgene expression further enhanced
      BM engraftment, but was associated with a significant increase in apoptosis of
      transduced cells in BM and reduced release of transduced leukocytes into PB. We
      conclude that increased apoptosis of mature myeloid cells in WHIM is secondary to
      a failure of marrow release and progression to normal myeloid cell senescence,
      and not a direct effect of activation of mutated CXCR4.

PMID- 16946302
TI  - Long-term outcome of patients given transplants of mobilized blood or bone
      marrow: A report from the International Bone Marrow Transplant Registry and the
      European Group for Blood and Marrow Transplantation.
AB  - We previously compared outcomes after allogeneic peripheral-blood stem cell
      (PBSC) and bone marrow (BM) transplantation in 706 patients with leukemia. We
      obtained long-term follow up on 413 of 491 patients who were alive at the time of
      the initial report: 141 PBSC and 272 BM recipients. Chronic graft-versus-host
      disease (GVHD) was more frequent after PBSC compared to BM transplantation (RR
      1.65, P < .001) yet relapse rates were similar in both groups. Leukemia-free
      survival rates were higher after PBSC than BM transplantation for patients with
      advanced chronic myeloid leukemia (33% versus 25%) but lower for those in first
      chronic phase (41% versus 61%) due to higher rates of late transplant-related
      mortality. Leukemia-free survival was similar after PBSC and BM transplantation
      for acute leukemia. These data represent the early experience with PBSC grafts.
      Long-term outcomes in recipients of more recent transplants are required to
      better evaluate the role of PBSC grafts relative to BM transplantation.

PMID- 16946303
TI  - Role of phosphatidylinositol 3'-kinase/AKT pathway in diffuse large B-cell
      lymphoma survival.
AB  - Phosphatidylinositol 3'-kinase (PI3K) is a key player in cell-growth signaling in
      a number of lymphoid malignancies, but its role in diffuse large B-cell lymphoma
      (DLBCL) has not been fully elucidated. Therefore, we investigated the role of the
      PI3K/AKT pathway in a panel of 5 DLBCL cell lines and 100 clinical samples.
      Inhibition of PI3K by a specific inhibitor, LY294002, induced apoptosis in
      SUDHL4, SUDHL5, and SUDHL10 (LY-sensitive) cells, whereas SUDHL8 and OCI-LY19 (LY
      resistant) cells were refractory to LY294002-induced apoptosis. AKT was
      phosphorylated in 5 of 5 DLBCL cell lines and inhibition of PI3K caused
      dephosphorylation/inactivation of constitutively active AKT, FOXO transcription
      factor, and GSK3 in LY-sensitive cell lines. In addition, there was a decrease in
      the expression level of inhibitory apoptotic protein, XIAP, in the DLBCL cell
      lines sensitive to LY294002 after treatment. However, no effect was observed in
      XIAP protein levels in the resistant DLBCL cell lines following LY294002
      treatment. Finally, using immunohistochemistry, p-AKT was detected in 52% of
      DLBCL tumors tested. Furthermore, in univariate analysis, high p-AKT expression
      was associated with short survival. In multivariate analysis, this correlation
      was no longer significant. Altogether, these results suggest that the PI3K/AKT
      pathway may be a potential target for therapeutic intervention in DLBCL.

PMID- 16946304
TI  - Maintenance therapy with rituximab leads to a significant prolongation of
      response duration after salvage therapy with a combination of rituximab,
      fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with
      recurring and refractory follicular and mantle cell lymphomas: Results of a
      prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG).
AB  - In follicular lymphoma (FL) and mantle cell lymphoma (MCL) the monoclonal
      antibody rituximab (R) improves the prognosis when combined with chemotherapy.
      The present study investigated R-maintenance after R-chemotherapy. Patients with
      recurring or refractory FL and MCL were randomized to 4 courses of fludarabine,
      cyclophosphamide, and mitoxantrone (FCM) alone or combined with R (R-FCM).
      Responding patients underwent a second randomization for R-maintenance comprising
      2 further courses of 4-times-weekly doses of R after 3 and 9 months. The first
      randomization was stopped after 147 patients, when R-FCM revealed a significantly
      better outcome. All subsequent patients received R-FCM. Of the 176 patients who
      are currently evaluable (as of October 2005), 138 received R-FCM for remission
      induction. Response duration was significantly prolonged by R-maintenance after R
      FCM, with the median not being reached in this evaluation versus an estimated
      median of 16 months (P = .001). This beneficial effect was also observed when
      analyzing FL (P = .035) and MCL (P = .049) separately. Hence, R-maintenance is
      effective after salvage with R-chemotherapy and significantly prolongs response
      duration in patients with recurring or refractory FL or MCL.

PMID- 16946305
TI  - JAK2(V617F): Prevalence in a large Chinese hospital population.
AB  - Recently, the JAK2(V617F) mutation was found in patients with myeloproliferative
      disorders (MPDs), including most with polycythemia vera (PV). The mutant JAK2 has
      increased kinase activity, and it was shown to be pathogenic in mouse models.
      Herein, we analyzed blood samples randomly collected from a clinical laboratory.
      Surprisingly, as many as 37 samples from a total of 3935 were found positive for
      the JAK2 mutation. However, only one of these samples had blood test results
      indicative for probable PV, but several had nonhematologic diseases. On average,
      samples with the mutation had normal red cell counts but significantly higher
      white blood cell and platelet counts, although most were within the normal range.
      The data suggest that the JAK2(V617F) mutation is apparently much more common
      than MPDs. Its occurrence may be a prelude to full blood cell abnormalities and
      other diseases, but it cannot by itself diagnose MPDs.

PMID- 16946306
TI  - Continuous in vivo infusion of interferon-gamma (IFN-gamma) enhances engraftment
      of syngeneic wild-type cells in Fanca-/- and Fancg-/- mice.
AB  - Fanconi anemia (FA) is a heterogeneous genetic disorder characterized by bone
      marrow (BM) failure and cancer susceptibility. Identification of the cDNAs of FA
      complementation types allows the potential of using gene transfer technology to
      introduce functional cDNAs as transgenes into autologous stem cells and provide a
      cure for the BM failure in FA patients. However, strategies to enhance the
      mobilization, transduction, and engraftment of exogenous stem cells are required
      to optimize efficacy prior to widespread clinical use. Hypersensitivity of Fancc
      /- cells to interferon-gamma (IFN-gamma), a nongenotoxic immune-regulatory
      cytokine, enhances engraftment of syngeneic wild-type (WT) cells in Fancc-/-
      mice. However, whether this phenotype is of broad relevance in other FA
      complementation groups is unresolved. Here we show that primitive and mature
      myeloid progenitors in Fanca-/- and Fancg-/- mice are hypersensitive to IFN-gamma
      and that in vivo infusion of IFN-gamma at clinically relevant concentrations was
      sufficient to allow consistent long-term engraftment of isogenic WT repopulating
      stem cells. Given that FANCA, FANCC, and FANCG complementation groups account for
      more than 90% of all FA patients, these data provide evidence that IFN-gamma
      conditioning may be a useful nongenotoxic strategy for myelopreparation in FA
      patients.

PMID- 16946308
TI  - Introduction of bovine tuberculosis to north-east England by bought-in cattle.
AB  - The source of bovine tuberculosis was investigated in 31 herds in north-east
      England that experienced confirmed breakdowns between January 2002 and June 2004;
      nine of the herds had been restocked after the UK outbreak of foot-and-mouth
      disease in 2001. In all but one of the breakdowns the most likely source of
      infection was identified as one or more purchased animals. In 17 of the
      breakdowns, reactor animals were traced to herds from which the same combination
      of spoligotype and variable number tandem repeats was isolated, and in five
      breakdowns a different spoligotype was isolated. The most likely sources were
      located in Wales and the west and north of England, and included a Cheshire herd
      that was the most likely source of nine of the breakdowns. Three breakdowns were
      traced to Irish imports. Reactors in five of the breakdowns included homebred as
      well as purchased animals, providing evidence for the likely spread of the
      disease within the herds. The lack of geographical clustering of molecular types
      pointed to the overwhelming source of infection being cattle that had been bought
      in.

PMID- 16946307
TI  - Mitochondrial DNA sequence variation in single cells from leukemia patients.
AB  - A high frequency of mtDNA somatic mutation has been observed in many tumors as
      well as in aging tissues. In this study, we analyzed the mtDNA control region
      sequence variation in 3534 single normal cells and individual blasts from 18
      patients with leukemia and 10 healthy donors, to address the mutation process in
      leukemic cells. We found significant differences in mtDNA sequence, as
      represented by the number of haplotypes and the mean number of cells with each
      nonaggregate haplotype in a population of cells, in patients compared to
      controls. Patients with similar clinical leukemia types, particularly acute
      myeloid leukemia (AML), did not show a uniform pattern of sequence variation in
      single blasts. Some patients at relapse presented a complex shift of major
      haplotypes in single cells. Four patients showed high frequencies of cells
      containing mutations 189, 260, 16150, and 16488, respectively, as a result of
      clonal expansion and could be considered as potential markers for their
      respective disease progression. To our knowledge, this is the first large-scale
      study of mtDNA variation in single malignant cells. Our results suggest that the
      somatic mutation process in leukemia is complex, leading to diverse levels of
      genetic alterations due to either intrinsic aspects of leukemia pathophysiology
      or chemotherapy effects.

PMID- 16946309
TI  - Epidemiology of salmonella infections in pig units and antimicrobial
      susceptibility profiles of the strains of Salmonella species isolated.
AB  - One hundred and thirteen finishing pig units and 74 sow units in Catalonia,
      Spain, were examined to determine the prevalence of salmonella infections and the
      factors that could be associated with them. Pooled faecal samples were taken from
      the finishing units, and samples of faeces were collected from individual sows.
      The Salmonella isolates were serotyped, phage typed and examined for their
      antimicrobial susceptibility to 18 common antimicrobial drugs. In addition, blood
      samples from pigs on 141 farms were analysed by ELISA. In both the
      bacteriological and serological surveys, a questionnaire with 84 questions was
      completed for each farm. Salmonella species were isolated from 20 per cent of the
      finishing units and 24 per cent of the sow units; 14 serotypes were detected in
      the finishing pigs and 11 in the sows. More than 30 per cent of the strains were
      resistant to tetracycline, sulphonamides, ampicillin or streptomycin, and 69 per
      cent of the strains were resistant to three or more agents up to 10 compounds.
      Seventy-seven per cent of the farms had at least one seropositive animal, and 26
      per cent of these farms had an individual seroprevalence of 50 per cent or more.
      The factors associated (P<0.05) with the excretion of Salmonella species in the
      finishing units were the practice of raising livestock other than pigs (odds
      ratio [OR]=6.18), the herd size (OR=5.87), and a past history of clinical
      salmonellosis (OR=4.97). For the sows, the factors associated (P<0.05) with the
      excretion of Salmonella species were having open-flushed drainage of sewage
      (OR=34.48), a lack of rodent control measures (OR=0.05) and the number of sows in
      the unit (OR=9.26). Factors associated with seropositivity in the finishing units
      were a lack of bird-proof nets (OR=0.30) and the use of water from private wells
      (OR=3.64).

PMID- 16946310
TI  - Study of the effects of once daily doses of trilostane on cortisol concentrations
      and responsiveness to adrenocorticotrophic hormone in hyperadrenocorticoid dogs.
AB  - The effects of trilostane, a 3beta-hydroxysteroid dehydrogenase inhibitor on
      basal cortisol concentrations and the results of ACTH stimulation tests in dogs
      with pituitary-dependent hyperadrenocorticism were investigated. In eight of nine
      dogs trilostane suppressed the concentration of cortisol below the lower limit of
      the reference range (<50 nmol/l) for a mean (sd) of 3.5 (2.3) hours during the
      day, but for no longer than 13 hours. In another 10 dogs, there was a clear
      difference between the post ACTH cortisol concentrations observed four and 24
      hours after the administration of trilostane. Furthermore, in the six dogs whose
      clinical signs were poorly controlled the post-ACTH concentrations observed four
      and 24 hours after the administration of trilostane were always higher than the
      equivalent cortisol concentrations in the four dogs whose clinical signs were
      controlled. A short duration of drug action may be responsible for the failure of
      some dogs to respond adequately to once daily trilostane administration.

PMID- 16946311
TI  - Susceptibility of fungi isolated from the respiratory tract of falcons to
      amphotericin B, itraconazole and voriconazole.
AB  - The minimum inhibitory concentrations (mics) of fungi isolated from the air sacs
      of falcons before (group 1), and during antifungal treatment with amphotericin B
      nebulisation and oral itraconazole or voriconazole (group 2), or with
      itraconazole alone (group 3) or voriconazole alone (group 4) were determined.
      Before treatment, 95 per cent of the isolates, including Aspergillus fumigatus,
      Aspergillus flavus, Aspergillus niger and Aspergillus terreus, were susceptible
      to voriconazole at mics up to 0.38 microg/ml, and all the isolates were
      susceptible at mics up to 1 microg/ml. Before treatment, 21 per cent of the
      isolates, including A fumigatus (27.6 per cent), A flavus (16.6 per cent), A
      niger (100 per cent) and A terreus (23 per cent), were resistant (mic > or =1
      microg/ml) to itraconazole; 51 per cent of the isolates, including A fumigatus
      (31 per cent), A flavus (78 per cent), A niger (14 per cent) and A terreus (77
      per cent), had mics of over 1 microg/ml to amphotericin B, and after treatment
      their mics increased significantly. In contrast, there were no significant
      differences between the mics of voriconazole and itraconazole for the different
      Aspergillus species before and during treatment with these antifungal agents.

PMID- 16946312
TI  - Potential sources of infection for BSE cases born in France after 1996.

PMID- 16946313
TI  - Lipoptena cervi (deer ked) in two naturally infested dogs.

PMID- 16946315
TI  - New genotype of infectious bronchitis virus in chickens in Scotland.

PMID- 16946314
TI  - Diagnosis of olfactory neuroblastoma in a dog by magnetic resonance imaging.

PMID- 16946317
TI  - Trade in wild birds.

PMID- 16946318
TI  - Managing minor head injury in children.

PMID- 16946319
TI  - Growing pains.

PMID- 16946320
TI  - Restless legs syndrome.

PMID- 16946321
TI  - A prescription for better prescribing.

PMID- 16946322
TI  - Prevention of psychosocial problems in adolescence.

PMID- 16946323
TI  - Derbyshire village wins court battle.

PMID- 16946324
TI  - FDA finally approves Plan B--but with restrictions.

PMID- 16946326
TI  - England's cancer plan needs an overhaul, think tank says.

PMID- 16946327
TI  - Waits for diagnostic tests threaten 18 week treatment target.

PMID- 16946328
TI  - More than 12 million adults in England will be obese by 2010.

PMID- 16946330
TI  - Floods wreak havoc in East Africa.

PMID- 16946331
TI  - Maternity unit is criticised again for high mortality.

PMID- 16946332
TI  - Bush tells federal agencies to gather and share data on health quality and cost.

PMID- 16946333
TI  - Israel Medical Association condemns attacks on hospitals--but not Israel's use of
      cluster bombs.

PMID- 16946334
TI  - On a mission: how Cuba uses its doctors abroad.

PMID- 16946335
TI  - Prevention and early detection of vascular complications of diabetes.

PMID- 16946336
TI  - Biochemical "liver function tests".

PMID- 16946338
TI  - Preventing development of allergic disorders in children.

PMID- 16946339
TI  - Common paediatric problems.

PMID- 16946340
TI  - Role of cholinesterase inhibitors in dementia care needs rethinking.

PMID- 16946341
TI  - Are the dangers of childhood food allergy exaggerated?

PMID- 16946342
TI  - Are the dangers of childhood food allergy exaggerated?

PMID- 16946343
TI  - Where next for China? User fees increase China's health challenges.

PMID- 16946344
TI  - Where next for China? Keep to the basic principles of critical appraisal.

PMID- 16946345
TI  - Where next for China? Rising inequalities in health and wealth are biggest
      challenge.

PMID- 16946346
TI  - Spironolactone and risk of upper gastrointestinal events: spironolactone may not
      be guilty.

PMID- 16946347
TI  - Where next for China? Doctors' consciences are called on.

PMID- 16946348
TI  - Where next for China? Rose tinted spectacles do not help.

PMID- 16946349
TI  - Where next for China? Birth ratio in India is also dwindling.

PMID- 16946350
TI  - Avoid delaying surgery in patients with severe ulcerative colitis.

PMID- 16946351
TI  - Spironolactone and risk of upper gastrointestinal events: causality remains
      unconvincing.

PMID- 16946352
TI  - Spironolactone and risk of upper gastrointestinal events: association is
      unproved.

PMID- 16946353
TI  - Deaths from pesticide poisoning: a global response.
AB  - Self-poisoning with pesticides accounts for about a third of all suicides
      worldwide. To tackle this problem, the World Health Organization announced a
      global public health initiative in the second half of 2005. Planned approaches
      were to range from government regulatory action to the development of new
      treatments for pesticide poisoning. With broad-based support, this strategy
      should have a major impact on the global burden of suicide.

PMID- 16946354
TI  - Insight in psychosis and neuropsychological function: meta-analysis.
AB  - BACKGROUND: One factor contributing to impaired awareness of illness (poor
      insight) in psychotic disorders may be neurocognitive deficits. METHOD: A
      systematic review and meta-analysis were conducted after data extraction.
      Following an overall analysis, in which measures of different cognitive domains
      were taken together, more fine-grained analyses investigated whether there was a
      specific relation with frontal executive functioning, and whether this was
      influenced by diagnosis or the insight scales used. RESULTS: There was a
      significant mean correlation between insight ratings and neurocognitive
      performance (mean weighted r=0.17, 95% CI 0.13-0.21, z=8.3, P<0.0001), based on
      35 studies with a total of 2354 individuals. Further analyses revealed that the
      effect of general intellectual impairment was smaller than the specific
      association with executive function. This was only the case for psychosis in
      general, and not in an analysis limited to schizophrenia, where all cognitive
      domains were associated with impaired insight to a similar degree. CONCLUSIONS:
      Neuropsychological dysfunction, specifically impairment of set-shifting and error
      monitoring, contributes to poor insight in psychosis. Specific relations with
      different dimensions of insight and the putative role of metacognitive functions
      require further study.

PMID- 16946355
TI  - Strategies for discontinuing long-term benzodiazepine use: meta-analysis.
AB  - BACKGROUND: The prevalence of benzodiazepine consumption in European countries
      remains at 2-3% of the general population despite the well-documented
      disadvantages of long-term use. AIMS: To review systematically the success rates
      of different benzodiazepine discontinuation strategies. METHOD: Meta-analysis of
      comparable intervention studies. RESULTS: Twenty-nine articles met inclusion
      criteria. Two groups of interventions were identified; minimal intervention (e.g.
      giving simple advice in the form of a letter or meeting to a large group of
      people; n=3), and systematic discontinuation (defined as treatment programmes led
      by a physician or psychologist; n=26). Both were found to be significantly more
      effective than treatment as usual: minimal interventions (pooled OR=2.8, 95% CI
      1.6-5.1); systematic discontinuation alone (one study, OR=6.1, 95% CI 2.0-18.6).
      Augmentation of systematic discontinuation with imipramine (two studies, OR=3.1,
      95% CI 1.1-9.4) or group cognitive-behavioural therapy for patients with insomnia
      (two studies, OR=5.5, 95% CI 2.3-14.2) was superior to systematic discontinuation
      alone. CONCLUSIONS: Evidence was found for the efficacy of stepped care (minimal
      intervention followed by systematic discontinuation alone) in discontinuing long
      term benzodiazepine use.

PMID- 16946356
TI  - Grey matter correlates of minor physical anomalies in the AeSOP first-episode
      psychosis study.
AB  - BACKGROUND: Minor physical anomalies are more prevalent among people with
      psychosis. This supports a neurodevelopmental aetiology for psychotic disorders,
      since these anomalies and the brain are both ectodermally derived. However,
      little is understood about the brain regions implicated in this association.
      AIMS: To examine the relationship between minor physical anomalies and grey
      matter structure in a sample of patients with first-episode psychosis. METHOD:
      Sixty patients underwent assessment of minor physical anomalies with the Lane
      scale. High-resolution magnetic resonance images and voxel-based methods of image
      analysis were used to investigate brain structure in these patients. RESULTS: The
      total anomalies score was associated with a grey matter reduction in the
      prefrontal cortex and precuneus and with a grey matter excess in the basal
      ganglia, thalamus and lingual gyrus. CONCLUSIONS: Minor physical anomalies in a
      sample of patients with first-episode psychosis are associated with regional grey
      matter changes. These regional changes may be important in the pathogenesis of
      psychotic disorder.

PMID- 16946357
TI  - Substance misuse in first-episode psychosis: 15-month prospective follow-up
      study.
AB  - BACKGROUND: Well-designed prospective studies of substance misuse in first
      episode psychosis can improve our understanding of the risks associated with
      comorbid substance misuse and psychosis. AIMS: To examine the potential effects
      of substance misuse on in-patient admission and remission and relapse of positive
      symptoms in first-episode psychosis. METHOD: The study was a prospective 15-month
      follow-up investigation of 103 patients with first-episode psychosis recruited
      from three mental health services. RESULTS: Substance misuse was independently
      associated with increased risk of in-patient admission, relapse of positive
      symptoms and shorter time to relapse of positive symptoms after controlling for
      potential confounding factors. Substance misuse was not associated with remission
      or time to remission of positive symptoms. Heavy substance misuse was associated
      with increased risk of in-patient admission, relapse and shorter time to relapse.
      CONCLUSIONS: Substance misuse is an independent risk factor for a problematic
      recovery from first-episode psychosis.

PMID- 16946358
TI  - Untreated illness and outcome of psychosis.
AB  - BACKGROUND: There has been controversy as to whether early intervention in
      psychosis can improve the outcome of the disorder. AIMS: To establish if there is
      an association between duration of untreated psychosis and the 4-year outcome of
      persons with a first episode of psychosis. METHOD: Prospective naturalistic
      follow-up study of the outcome of consecutive first presentations with DSM-IV
      psychosis attending a community-based psychiatric service. RESULTS: A longer
      duration of untreated psychosis was associated with a significantly poorer
      functional and symptomatic outcome 4 years later. For schizophrenia and
      schizophreniform disorder, each increment in duration of untreated psychosis was
      associated with a 7.8 point decrease in global functioning and an increase in
      positive symptoms scores by 1.9 points. CONCLUSIONS: This study extends the
      findings of short-term follow-up studies by confirming an association between
      duration of untreated psychosis and 'mid-term' outcome.

PMID- 16946359
TI  - Outcome of major depression in Ethiopia: population-based study.
AB  - BACKGROUND: The outcome and impact of major depression in developing countries
      are not clear. AIMS: To describe the outcome of major depression and compare the
      disability and patterns of service use among different outcome groups. METHOD: In
      a case cohort study, nested within a population-based survey of 68,000
      participants using the Composite International Diagnostic Interview (CIDI), 300
      participants were randomly selected from those with current major depression and
      300 from those with no lifetime history. Participants were re-interviewed after
      18-62 months to ascertain current diagnosis, psychological symptoms, disability
      and use of health services. RESULTS: Of participants with major depression at
      baseline 26% also met criteria for major depression at follow up. Mortality ratio
      standardised for age and gender was 3.55 (95% C11.97 to 6.39). All indices of
      measure of disability were significantly higher in the persistently depressed
      group compared with the completely recovered group. Participants who had
      recovered partially resembled participants with persistent depression. Two-thirds
      of those with persistent depression had not sought any help. CONCLUSIONS: Major
      depression was associated with mortality and disability. Those with residual
      symptoms remained disabled. Help-seeking was unusual.

PMID- 16946360
TI  - Relationship between disabling fatigue and depression in children: genetic study.
AB  - BACKGROUND: Medically unexplained disabling fatigue in young people is familial
      and frequently associated with depressed mood. AIMS: To examine the degree of
      sharing of genetic and environmental influences on the symptoms of depression and
      fatigue in this age group. METHOD: The parents of twins aged 8-17 years, derived
      from a population-based register, completed a questionnaire regarding lifetime
      ever disabling fatigue in both twins. Twins aged 11 years or over completed the
      Mood and Feelings Questionnaire. The genetic and environmental influences on
      fatigue and the relationship with depression were examined using bivariate
      genetic analysis. RESULTS: Parent-rated data were obtained for 1468 twin pairs
      (65%) and self-rated data from 930 older twin pairs (58%). Bivariate analysis of
      fatigue and depression suggested that genetic and environmental influences on
      disabling fatigue were mainly specific to fatigue. CONCLUSIONS: Unexplained
      disabling fatigue in childhood is substantially familial and has mainly an
      independent aetiology from depression.

PMID- 16946361
TI  - Cognitive impairment in bipolar II disorder.
AB  - BACKGROUND: Persistent impairments in neurocognitive function have been described
      in bipolar disorder. AIMS: To compare the cognitive performance of patients with
      bipolar II disorder with that of patients with bipolar I disorder and a healthy
      control group. METHOD: The study included 71 euthymic patients with bipolar
      disorder (38 bipolar I, 33 bipolar II), who were compared on clinical and
      neuropsychological variables (e.g. executive function, attention, verbal and
      visual memory) and contrasted with 35 healthy controls on cognitive performance.
      RESULTS: Compared with controls, both bipolar groups showed significant deficits
      in most cognitive tasks including working memory (DigitSpan Backwards, P=0.002)
      and attention (DigitSpan Forwards, P=0.005; Trail Making Test, P=0.001). Those
      with type II disorders had an intermediate level of performance between the
      bipolar I group and the control group in verbal memory (P<0.005) and executive
      functions (Stroop interference task, P=0.020). CONCLUSIONS: Cognitive impairment
      exists in both subtypes of bipolar disorder, although more so in the bipolar I
      group. The best predictors of poor psychosocial functioning in bipolar II
      disorder were subclinical depressive symptoms, early onset of illness and poor
      performance on a measure related to executive function.

PMID- 16946362
TI  - Cerebral emboli and depressive symptoms in dementia.
AB  - BACKGROUND: The vascular depression hypothesis and our recent findings of
      increased frequency of spontaneous cerebral emboli in dementia suggest that such
      emboli may be involved in the causation of depressive symptoms in dementia. AIMS:
      To evaluate the association between spontaneous cerebral emboli and depressive
      symptoms in Alzheimer's disease and vascular dementia. METHOD: In a cohort of 142
      patients with dementia (72 with Alzheimer's disease and 70 with vascular
      dementia), the association between spontaneous cerebral emboli and clinically
      relevant depressive symptoms was examined using multiple logistic regression
      analyses. RESULTS: Spontaneous cerebral emboli were significantly more frequent
      in the patients with clinically relevant depressive symptoms (66 v. 37%, P=0.03).
      After adjustment for age, gender, Mini-Mental State Examination score, type of
      dementia and significant cardiovascular risk factors, the relationship remained
      significant (OR=3.47, 95% CI 1.10-10.97). CONCLUSIONS: Spontaneous cerebral
      emboli are associated with clinically relevant depressive symptoms in dementia,
      and further research is needed to explore the nature of this relationship.

PMID- 16946363
TI  - Escitalopram and paroxetine in the treatment of generalised anxiety disorder:
      randomised, placebo-controlled, double-blind study.
AB  - BACKGROUND: It is uncertain whether higher doses of selective serotonin reuptake
      inhibitors have greater efficacy in generalised anxiety disorder. AIMS: To assess
      the efficacy of different doses of escitalopram in generalised anxiety disorder.
      METHOD: Randomised, double-blind, placebo-controlled, fixed-dose, parallel-group,
      12-week study, with 681 patients: placebo (n=139); escitalopram, 5 mg/day,
      (n=134); 10 mg/day (n=136); 20 mg/day (n=133); paroxetine, 20 mg/day (n=139).
      RESULTS: Mean change in the primary efficacy measure was greater with
      escitalopram 10 and 20 mg than with placebo; 10 mg was more efficacious than
      paroxetine. Paroxetine was superior to placebo on some secondary measures, at
      some time points. Compared with placebo, more patients withdrew because of
      adverse events with escitalopram 20 mg and paroxetine. CONCLUSIONS: Escitalopram
      was efficacious in generalised anxiety disorder, 20 was not significantly
      superior to 10 mg/day. Escitalopram 10 mg was more efficacious than paroxetine.

PMID- 16946364
TI  - Internet information-seeking in mental health: population survey.
AB  - BACKGROUND: A major use of the of the internet is for health information-seeking.
      There has been little research into its use in relation to mental health. AIMS:
      To investigate the prevalence of internet use for mental health information
      seeking and its relative importance as a mental health information source.
      METHOD: General population survey. Questions covered internet use, past
      psychiatric history and the 12-item General Health Questionnaire. RESULTS:
      Eighteen per cent of all internet users had used the internet for information
      related to mental health. The prevalence was higher among those with a past
      history of mental health problems and those with current psychological distress.
      Only 12% of respondents selected the internet as one of the three most accurate
      sources of information, compared with 24% who responded that it was one of the
      three sources they would use. CONCLUSIONS: The internet has a significant role in
      mental health information-seeking. The internet is used more than it is trusted.

PMID- 16946365
TI  - Physical vulnerability and fatal self-harm in the elderly.
AB  - Although the high rate of suicide in elderly people is conventionally explained
      as being due to greater intent to die, we have noted elderly Sri Lankans dying
      after relatively mild poisoning. Using data from cases of yellow oleander
      poisoning, we investigated the effect of age on outcome in 1697 patients,
      controlling for gender and amount ingested. In fully adjusted models, people over
      64 years old were 13.8 (95% CI 3.6-53.0) times more likely to die than those less
      than 25 years old. The high number of suicides in elderly people globally is
      likely to be due, in part, to the difficulty they face in surviving the effects
      of both the poisoning and its treatment.

PMID- 16946367
TI  - Vagus nerve stimulation in chronic treatment-resistant depression: preliminary
      findings of an open-label study.
AB  - We evaluated the efficacy and safety of vagus nerve stimulation therapy in the
      treatment of 11 patients with chronic treatment-resistant depression. Mood was
      evaluated at frequent intervals over the year following implantation. All
      measures of depression, including the Hamilton Rating Scale for Depression
      reduced significantly. The response and remission rates were 55% and 27%
      respectively at 1 year. Side-effects were common, and some were severe.

PMID- 16946366
TI  - Attention to the eyes and fear-recognition deficits in child psychopathy.
AB  - The ability to recognise fear is impaired in people with damage to the amygdala
      and, interestingly, in adult psychopathy. Here we confirm that deficits in
      recognising fear exist in children with psychopathic traits. We show for the
      first time that, as with patients with amygdala damage, this deficit can be
      temporarily corrected by simply asking them to focus on the eyes of other people.
      These data support models of psychopathy that emphasise specific dysfunction of
      the amygdala and suggest an innovative approach for intervening early in the
      development of psychopathy.

PMID- 16946369
TI  - Explanatory models of schizophrenia.

PMID- 16946370
TI  - Risk factors for coronary heart disease in people with severe mental illness.

PMID- 16946372
TI  - Restarting clozapine following leucopenia or neutropenia.

PMID- 16946374
TI  - Good and bad lessons from the United States.

PMID- 16946375
TI  - Good doctors: safer patients--the Chief Medical Officer's prescription for
      regulating doctors.

PMID- 16946376
TI  - The impact of surgical care practitioners on surgical training.

PMID- 16946377
TI  - Trends in obesity.

PMID- 16946378
TI  - Open access: the evidence and the verdict.

PMID- 16946379
TI  - Reasons for optimism not disillusionment.

PMID- 16946380
TI  - Controversies in thromboprophylaxis for immobile patients secondary to
      neurological impairment.

PMID- 16946381
TI  - Depression: epidemic or pseudo-epidemic?

PMID- 16946382
TI  - International medical graduates.

PMID- 16946383
TI  - Al-Razi and Islamic medicine in the 9th century.

PMID- 16946384
TI  - Open access, UK PubMed Central and the Wellcome Trust.

PMID- 16946385
TI  - The life and death of Private Harry Farr.

PMID- 16946386
TI  - The use of anaesthesia to diagnose malingering in the 19th century.

PMID- 16946387
TI  - The Valsalva manoeuvre and Antonio Valsalva (1666-1723).

PMID- 16946388
TI  - The highly profitable but unethical business of publishing medical research.

PMID- 16946389
TI  - The metabolic syndrome.

PMID- 16946390
TI  - Diabetes management in the USA and England: comparative analysis of national
      surveys.
AB  - OBJECTIVES: To compare diabetes management in adults between England and the
      United States, particularly focusing on the impact of a universal access health
      insurance system. DESIGN: Analysis of the nationally-representative surveys
      Health Survey of England, 2003 (unweighted n =14 057) and the National Health and
      Nutrition Examination Survey, 2001-2002 (unweighted n =5411). SETTING AND
      PARTICIPANTS: Adults 20-64 years of age; individuals >65. MAIN OUTCOME MEASURES:
      Glycaemic, lipid and blood pressure control and medication use among individuals
      with previously diagnosed diabetes. RESULTS: Among those aged 20-64 the
      prevalence of diagnosed diabetes was lower in England (2.7%) than in the USA
      (5.0%). The proportion with diabetes receiving treatment was similar for the two
      countries. However, the mean HbA1c in England was 7.6%: in the USA it was 7.5%
      for those with insurance and 8.6% for those without insurance. The proportion of
      individuals on ACE inhibitors in England was 39%: in USA it was 39% for those
      with insurance, and 14% for those without. CONCLUSIONS: Individuals in a
      healthcare system providing universal access have better managed diabetes than
      those in a market based system once one accounts for insurance.

PMID- 16946391
TI  - Comparison of reports of randomized controlled trials and systematic reviews in
      surgical journals: literature review.
AB  - OBJECTIVES: Randomized controlled trials and systematic reviews of such trials
      are the gold standard for assessing the effectiveness of interventions. There
      have been concerns about the anecdotal evidence underpinning many of the
      interventions used and introduced into surgical care. The American College of
      Surgeons has prioritized the need for more trials and systematic reviews of
      trials. To investigate the assertion that the methodological quality of studies
      conducted in surgery is in general poor and to assess the possible impact of new
      policy developments in the US, we sought to compare the number and proportion of
      published randomized controlled trials and systematic reviews in the leading two
      US and UK general surgical journals. Two reviewers systematically and
      independently hand searched all issues of these journals over a 12-month period
      to identify randomised controlled trials and systematic reviews. DESIGN:
      Systematic searching and independent abstraction of data from all volumes of the
      top two general surgical journals published in the USA and the UK in 2004.
      SETTING: 519 original reports in UK journals and 616 original reports in USA
      journals. MAIN OUTCOME MEASURES: Number and proportion of randomized controlled
      trials and systematic reviews. RESULTS: Overall, the proportion of randomized
      controlled trials in all four journals was 5.6% (95% confidence interval [CI] 4.4
      7.0) and 5.2% (95% CI 4.1-6.7) for systematic reviews. For journals published in
      the UK 29/519 (5.6%) of the publications were reports of randomized controlled
      trials, and for the USA journals this figure was 34/616 (5.5%); odds ratio
      [OR]=0.99, 95%CI 0.6-1.6; P=0.96. Systematic reviews were significantly more
      commonly reported in the UK journals: UK 37/519 (7.1%) versus USA 22/616 (3.6%);
      OR=0.48, 95%CI 0.3-0.8; P<0.01. CONCLUSIONS: The concerns expressed almost a
      decade ago remain valid: there are still very few reports of randomized
      controlled trials and systematic reviews published in leading USA and UK surgical
      journals, with relatively little difference between these countries in the
      proportion of reported studies employing these designs. The American College of
      Surgeons initiative has yet to make an impact.

PMID- 16946392
TI  - Schistosomiasis of the appendix.

PMID- 16946393
TI  - Bilateral cavernous sinus thrombosis complicating sinusitis.

PMID- 16946394
TI  - The 1944 patulin trial of the British Medical Research Council.

PMID- 16946395
TI  - Podcasts: an educational revolution in the making?

PMID- 16946396
TI  - Treatment of viral and neoplastic diseases with double-stranded RNA derivatives
      and other new agents.
AB  - Many attempts have been made to inhibit viral and neoplastic diseases by
      targeting the RNA system. The pathophysiologic significance of the microRNA
      system and the therapeutic potential of its manipulation are discussed. Studies
      of double-stranded RNA derivatives are reviewed. The therapeutic potential of one
      of these compounds, polyI:MPC, is emphasized. Studies of other related antiviral
      and antineoplastic agents are discussed, including 2'-deoxyoligocytidilates and
      telomerase inhibitors.

PMID- 16946397
TI  - Flavonoids attenuate cardiovascular disease, inhibit phosphodiesterase, and
      modulate lipid homeostasis in adipose tissue and liver.
AB  - Plant flavonoids are widely distributed polyphenolic compounds of the human diet.
      They consist of six major classes based on specific structural differences:
      flavonols, flavones, flavanones, catechins, anthocyanidins, and isoflavones. All
      of the major classes of flavonoids are comprised of three six-membered rings: an
      aromatic A-ring fused to a heterocyclic C-ring that is attached through a single
      carbon-carbon bond to an aromatic Bring. Population studies have shown that
      flavonoid intake is inversely correlated with mortality from cardiovascular
      disease, and numerous flavonoids of dietary significance have been shown to
      beneficially impact parameters associated with atherosclerosis, including
      lipoprotein oxidation, blood platelet aggregation, and vascular reactivity.
      Therapeutic effects of flavonoids on platelet aggregability and blood pressure
      have been attributed to competitive inhibition of cyclic nucleotide
      phosphodiesterase (PDE), an elevation in cAMP level, and subsequent activation of
      protein kinase A (cAMP-dependent protein kinase). In addition, flavonoids may
      induce neutral lipid hydrolysis from lipid stores through PDE inhibition in
      adipose tissue and liver. Indeed, the three-dimensional structure of many
      flavonoids is sterically and electrostatically compatible with the catalytic site
      of cAMP PDE3 and PDE4. Flavonoids have also been reported to suppress pathways of
      lipid biosynthesis and of very low-density lipoprotein production in cultured
      hepatocytes. Continued studies of the biochemical mechanisms underlying the
      biological effects of plant flavonoids may uncover new strategies for the
      treatment of cardiovascular disease, as well as associated conditions such as
      obesity, hepatic steatosis, and Type 2 diabetes.

PMID- 16946398
TI  - Sodium pump reduction correlates with aortic clamp time in pediatric heart
      surgery.
AB  - Myocardial depression after cardiac surgery is modulated by cardiopulmonary
      bypass (CPB) and the underlying heart disease. The sodium pump is a key component
      for myocardial function. We hypothesized that the change in sodium pump
      expression during CPB correlates with intraoperative and postoperative laboratory
      and clinical parameters in neonates and children with various congenital heart
      defects. Sodium pump isoforms alpha1 (ATP1A1) and alpha3 (ATP1A3) mRNA expression
      in right atrial myocardium, excised before and after CPB, was quantified. Groups
      were assigned according to presence (VO group, n = 8) or absence (NO group, n =
      8) of right atrial volume overload. CPB and aortic clamp time correlated with
      postoperative troponin-I values and ICU stay. ATP1A1 (P = 0.008) and ATP1A3 (P =
      0.038) mRNA expression were significantly reduced during CPB. Longer aortic clamp
      times were associated with lower postoperative ATP1A1 (P = 0.045) and ATP1A3 (P =
      0.002) mRNA expression. Low postoperative ATP1A1 (P = 0.043) and ATP1A3 (P =
      0.002) expressions were associated with high troponin-I values. These results
      were restricted to the VO group. No correlation of sodium pump mRNA expression
      was found with the duration of ICU stay or ventilation. The postoperative
      troponin-I and clinical parameters correlated with the length of CPB, regardless
      of volume overload. In contrast, only dilated right atrium seemed to be
      susceptible to CPB in terms of sodium pump expression, showing a reduction during
      the operation and a correlation of sodium pump with postoperative troponin-I
      values.

PMID- 16946399
TI  - Dynamic adhesion of T lymphocytes to endothelial cells revealed by atomic force
      microscopy.
AB  - The recruitment of T lymphocytes to lymphoid organs or sites of inflammation is a
      crucial step in adaptive immunity. These processes require endothelial activation
      and expression of adhesion molecules, including E- and P-selectins, intercellular
      adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1).
      However, the complete characterization of the adhesion strength and dynamics
      between lymphocytes and endothelial cells has been hampered by the lack of
      sensitive quantitative techniques. Here we report on the application of atomic
      force microscopy to characterize the interaction between individual pairs of
      living T lymphocytes (i.e., Jurkat cells) and human umbilical vein endothelial
      cells (HUVECs). The detachment of individual cell-cell conjugates was a complex
      process involving several step-like rupture events and the viscoelastic
      deformation of cells on the scale of several microns. Adhesion between Jurkat
      cells and activated endothelial cells increased with compression force and
      contact time, with the most dramatic changes occurring within the first half
      second of contact. After 0.25 sec of contact, E-selectin, ICAM-1, and VCAM-1
      contributed to 18%, 39%, and 41% of total adhesion strength, respectively,
      suggesting that ICAM-1 and VCAM-1 contributed more than the selectins in
      supporting cell attachment.

PMID- 16946400
TI  - Expression and properties of recombinant ovine uterine serpin.
AB  - Ovine uterine serpin (OvUS) is produced in the uterus of sheep under the
      influence of progesterone. It weakly inhibits pepsin and reduces proliferation of
      lymphocytes, tumor cell lines, and preimplantation embryos. When purified from
      uterine fluid, the concentration required for its antiproliferative effect in
      vitro is approximately 0.25-1 mg/ml. Here we show that recombinant (r) OvUS is a
      more potent regulator of cell proliferation than native (n) OvUS purified from
      uterine fluid. To produce rOvUS, RNA was extracted from endometrium from a
      pregnant ewe and cDNA was amplified by reverse transcription-polymerase chain
      reaction using gene-specific primers. The purified OvUS cDNA was inserted into
      the ampicillin-resistant plasmid vector pcDNA3.1/ V5-His-TOPO. The plasmid was
      introduced into the TOP10 Escherichia coli strain, purified, and used for
      transfection of Freestyle 293-F cells. Digestion of rOvUS with protein N
      glycosidase F confirmed that rOvUS was N-glycosylated. Both rOvUS and nOvUS
      inhibited proliferation of phytohemagglutin-activated sheep lymphocytes and the
      P388D1 mouse lymphoma and PC-3 prostate cell lines. Inhibition was greater for
      rOvUS than for nOvUS, and concentrations as low as 15 microg/ml rOvUS were
      effective at reducing lymphocyte proliferation. Addition of rOvUS to fertilized
      bovine embryos reduced the cleavage rate and the percentage of embryos that
      became blastocysts. Native OvUS did not affect cleavage rate and had a smaller
      effect on development to the blastocyst stage. Experiments demonstrate that OvUS
      is a more potent inhibitor of cell proliferation and embryonic development than
      previously believed and add credence to the putative role for the protein in
      regulating cell proliferation.

PMID- 16946401
TI  - Influence of osmolytes on in vivo glucose monitoring using optical coherence
      tomography.
AB  - Diabetes mellitus and its complications are the third leading cause of death in
      the world, exceeded only by cardiovascular disease and cancer. Tighter monitoring
      and control of blood glucose could minimize complications associated with
      diabetes. Recently, optical coherence tomography (OCT) for noninvasive glucose
      monitoring was proposed and tested in vivo. The aim of this work was to
      investigate the influence of changes in blood glucose concentration ([glu]) and
      sodium concentration ([Na+]) on the OCT signal. We also investigated the
      influence of other important analytes on the sensitivity of glucose monitoring
      with OCT. The experiments were carried out in anesthetized female pigs. The OCT
      images were acquired continuously from skin, while [glu] and [Na+] were
      experimentally varied within their physiological ranges. Correlations of the OCT
      signal slope with [glu] and [Na+] were studied at different tissue depths. The
      tissue area probed with OCT was marked and cut for histological examination. The
      correlation of blood [glu] and [Na+] with the OCT signal slope was observed in
      separate tissue layers. On average, equimolar changes in [glu] produced 2.26 +/-
      1.15 greater alterations of the OCT signal slope than changes in [Na+]. Variation
      of concentrations of other analytes did not influence the OCT signal slope. The
      influence of [Na+] on relative changes in the OCT signal slope was generally less
      than [glu]-induced changes. OCT is a promising method for noninvasive glucose
      monitoring because of its ability to track the influence of changing [glu] on
      individual tissue layers.

PMID- 16946402
TI  - Effects of commensal bacteria on intestinal morphology and expression of
      proinflammatory cytokines in the gnotobiotic pig.
AB  - A germ-free neonatal pig model was established to determine the effects of
      bacterial colonization by different species on small intestinal morphology and
      proinflammatory cytokine gene expression. Two experimental groups of 16 pigs were
      aseptically delivered by cesarian section and allocated into 4 gnotobiotic
      isolators. Pigs were either maintained germ-free (GF), or were orally inoculated
      with either a single strain of nonpathogenic Escherichia coli (EC) or
      Lactobacillus fermentum (LF) or conventionalized with adult porcine feces (CV).
      After 13 days tissue samples were collected at 5 regions corresponding to 5%,
      25%, 50%, 75%, and 95% of the small intestine (SI) length. In Experiment 2, the
      GF isolator became contaminated with Staphylococcus epidermidis (SE). In general,
      intestinal responses to bacterial colonization were similar among GF, LF, and SE
      pigs, and intestinal responses in EC pigs were more similar to CV pigs. Responses
      to bacterial colonization were most pronounced in the distal SI regions (50%
      95%), suggesting that nonmicrobial factors may be more important in the proximal
      SI. Relative to CV pigs, the distal intestines of GF, LF, and SE pigs were
      characterized by long villi, shallow crypts, increased relative intestinal mass,
      and decreased lamina propria cellularity, whereas SI morphology was intermediate
      in EC pigs. Relative expression of proinflammatory cytokines interleukin-1beta
      (IL-1beta ) and IL-6 generally increased distally in the SI and was highest in EC
      and CV pigs. We observed regional variation in SI morphology and proinflammatory
      cytokine expression, which differed with bacterial species. This study
      demonstrates that bacterial species differentially affect intestinal morphology
      and expression of proinflammatory cytokines and suggests that neonatal bacterial
      colonization patterns may have long-term effects on intestinal health and
      development.

PMID- 16946403
TI  - Accumulation of recombinant SARS-CoV spike protein in plant cytosol and
      chloroplasts indicate potential for development of plant-derived oral vaccines.
AB  - Plants are promising candidates as bioreactors for the production of oral
      recombinant proteins in the biopharmaceutical industry. As an initial step toward
      provision of an oral vaccine against the severe acute respiratory syndrome
      coronavirus (SARS-CoV), we have expressed a partial spike (S) protein of SARS-CoV
      in the cytosol of nuclear-transformed plants and in the chloroplasts of plastid
      transformed plants. In the construction of both nuclear and plastid
      transformation vectors, a 2-kilobase nucleotide sequence encoding amino acids 1
      658 of the SARS-CoV spike protein (S1) was modified with nucleotide changes, but
      not amino acid changes, to optimize codon usage for expression in plants. To
      investigate the subcellular localization of S1 during transient expression in
      tobacco leaves, a translational fusion consisting of S1 and the green fluorescent
      protein (GFP) was generated. Following agroinfiltration of tobacco leaves,
      analysis by laser confocal scanning microscopy revealed that the S1:GFP fusion
      protein was localized to the cytosol. In stable transgenic tobacco plants and
      lettuce plants generated by Agrobacterium-mediated transformation, tobacco and
      lettuce leaves were observed to express the S1 at high levels from the
      Cauliflower Mosaic Virus 35S promoter with Northern blot analysis. When the S1
      was expressed in transplastomic tobacco, S1 messenger RNA and its corresponding
      protein were detected on Northern and Western blot analyses, respectively. Our
      results demonstrate the feasibility of producing S1 in nuclear- and chloroplast
      transformed plants, indicating its potential in subsequent development of a plant
      derived and safe oral recombinant subunit vaccine against the SARS-CoV in edible
      plants.

PMID- 16946404
TI  - Antioxidants and phase 2 enzymes in cardiomyocytes: Chemical inducibility and
      chemoprotection against oxidant and simulated ischemia-reperfusion injury.
AB  - The increasing recognition of the role for oxidative stress in cardiac disorders
      has led to extensive investigation on the protection by exogenous antioxidants
      against oxidative cardiac injury. On the other hand, another strategy for
      protecting against oxidative cardiac injury may be through upregulation of the
      endogenous antioxidants and phase 2 enzymes in the myocardium by chemical
      inducers. However, our current understanding of the chemical inducibility of
      cardiac cellular antioxidants and phase 2 enzymes is very limited. In this study,
      using rat cardiac H9c2 cells we have characterized the concentration- and time
      dependent induction of cellular antioxidants and phase 2 enzymes by 3H-1,2
      dithiole-3-thione (D3T), and the resultant chemoprotective effects on oxidative
      cardiac cell injury. Incubation of H9c2 cells with D3T resulted in a marked
      concentration- and time-dependent induction of a number of cellular antioxidants
      and phase 2 enzymes, including catalase, reduced glutathione (GSH), GSH
      peroxidase, glutathione reductase (GR), GSH S-transferase (GST), and
      NAD(P)H:quinone oxidoreductase-1 (NQO1). D3T treatment of H9c2 cells also caused
      an increase in mRNA expression of catalase, gamma-glutamylcysteine ligase
      catalytic subunit, GR, GSTA1, M1 and P1, and NQO1. Moreover, both mRNA and
      protein expression of Nrf2 were induced in D3T-treated cells. D3T pretreatment
      led to a marked protection against H9c2 cell injury elicited by various oxidants
      and simulated ischemia-reperfusion. D3T pretreatment also resulted in decreased
      intracellular accumulation of reactive oxygen in H9c2 cells after exposure to the
      oxidants as well as simulated ischemia-reperfusion. This study demonstrates that
      a series of endogenous antioxidants and phase 2 enzymes in H9c2 cells can be
      induced by D3T in a concentration- and time-dependent fashion, and that the D3T
      upregulated cellular defenses are accompanied by a markedly increased resistance
      to oxidative cardiac cell injury.

PMID- 16946405
TI  - PPAR gamma ligand troglitazone lowers cholesterol synthesis in HepG2 and Caco-2
      cells via a reduced concentration of nuclear SREBP-2.
AB  - Cholesterol synthesis in animal cells is regulated by sterol regulatory element
      binding protein (SREBP)-2. The objective of this study was to investigate whether
      activation of peroxisome proliferator-activatedreceptor (PPAR)-gamma influences
      the SREBP-2 dependent cholesterol synthesis in liver and intestinal cells.
      Therefore, HepG2 and Caco-2 cells were incubated with and without 10 or 30 microM
      of troglitazone, a synthetic PPAR gamma agonist, for 4 hrs. Incubation with 10 or
      30 microM of troglitazone caused a significant, dose-dependent reduction of
      cholesterol synthesis in both HepG2 and Caco-2 cells (P < 0.05). HepG2 and Caco-2
      cells incubated with 10 or 30 microM of troglitazone had also lower mRNA
      concentrations and lower nuclear protein concentrations of SREBP-2 than untreated
      control cells (P < 0.05). mRNA concentrations of the SREBP-2 target genes HMG-CoA
      reductase and LDL receptor were also reduced in HepG2 and Caco-2 cells treated
      with 30 microM of troglitazone compared to control cells (P < 0.05). In
      conclusion, this study shows that PPAR gamma activation by troglitazone lowers
      the cholesterol synthesis in HepG2 and Caco-2 cells by reducing the concentration
      of nuclear SREBP-2 and successive downregulation of its target genes involved in
      cholesterol synthesis.

PMID- 16946406
TI  - Inhibition of dipeptidyl-peptidase IV does not increase circulating IGF-1
      concentrations in growing pigs.
AB  - The enzyme dipeptidyl peptidase-IV (DPP-IV) inactivates a variety of bioactive
      peptides, including glucagon-like peptide-1 (GLP-1) and growth hormone releasing
      hormone (GHRH). Inhibiting DPP-IV in order to increase circulating GLP-1 is of
      interest as a treatment for Type II diabetes. Inactivation of DPP-IV may also
      increase circulating GHRH, potentially enhancing growth in domestic animals. To
      test the hypothesis that inhibition of DPP-IV activity will influence the growth
      hormone/ IGF-1 axis, growing pigs (Sus scrofa domesticus, 78 kg) were treated
      with a DPP-IV inhibitor (Compound 1, the 2,5-difluor-ophenyl analog of the
      triazolopiperazine MK0431, sitagliptin), and plasma concentrations of IGF-1 were
      monitored. Pigs were administered either sterile saline (0.11 ml/kg followed by a
      continuous infusion at 2 ml/hr for 72 hrs, controls, n = 2), Compound 1 (2.78
      mg/kg followed by a continuous infusion at 0.327 mg/kg x hr for 72 hrs, n = 4) or
      GHRH (0.11 ml/kg sterile saline, followed by a continuous infusion of GHRH at 2.5
      microg/ kg x hr for 48 hrs, n = 4). Plasma concentrations of Compound 1 were
      maintained at 1 microM, which resulted in a 90% inhibition of circulating DPP-IV
      activity. Relative to the predose 24-hr period, area under the IGF-1
      concentration curve (AUC) tended to be lower (P = 0.062) with Compound 1 (.79 +/-
      130 ng/ml x hr) than controls (543 +/- 330 ng/ml x hr). GHRH treatment increased
      the IGF-1 AUC (1210 +/- 160 ng/ml x hr, P = 0.049 vs. controls and P = 0.001 vs.
      Compound 1). We conclude that inhibition of DPP-IV does not alter the circulating
      levels of IGF-1 in the growing pig.

PMID- 16946407
TI  - Physiologic and genomic analyses of nutrition-ethanol interactions during
      gestation: Implications for fetal ethanol toxicity.
AB  - Nutrition-ethanol (EtOH) interactions during gestation remain unclear primarily
      due to the lack of appropriate rodent models. In the present report we utilize
      total enteral nutrition (TEN) to specifically understand the roles of nutrition
      and caloric intake in EtOH-induced fetal toxicity. Time-impregnated rats were
      intragastrically fed either control or diets containing EtOH (8-14 g/kg/day) at a
      recommended caloric intake for pregnant rats or rats 30% undernourished, from
      gestation day (GD) 6-20. Decreased fetal weight and litter size (P < 0.05) and
      increased full litter resorptions (33% vs. 0%), were observed in undernourished
      dams compared to adequately fed rats given the same dose of EtOH, while
      undernutrition alone did not produce any fetal toxicity. Undernutrition led to
      impairment of EtOH metabolism, increased blood EtOH concentrations (160%), and
      decreased maternal hepatic ADH1 mRNA, protein, and activity. Microarray analyses
      of maternal hepatic gene expression on GD15 revealed that 369 genes were altered
      by EtOH in the presence of undernutrition, as compared to only 37 genes by EtOH
      per se (+/-2-fold, P < 0.05). Hierarchical clustering and gene ontology analysis
      revealed that stress and external stimulus responses, transcriptional regulation,
      cellular homeostasis, and protein metabolism were affected uniquely in the EtOH
      under-nutrition group, but not by EtOH alone. Microarray data were confirmed
      using real-time RT-PCR. Undernourished EtOH-fed animals had 2-fold lower IGF-1
      mRNA and 10-fold lower serum IGF-1 protein levels compared to undernourished
      controls (P < 0.0005). Examination of maternal GH signaling via STAT5a and -5b
      revealed significant reduction in both gene and protein expression produced by
      both EtOH and undernutrition. However, despite significantly elevated fetal BECs,
      fetal IGF-1 mRNA and protein were not affected by EtOH or EtOH-undernutrition
      combinations. Our data suggest that undernutrition potentiates the fetal toxicity
      of EtOH in part by disrupting maternal GH-IGF-1, signaling thereby decreasing
      maternal uterine capacity and placental growth.

PMID- 16946408
TI  - Mesenteric vascular responsiveness in a rat model of pregnancy-induced
      hypertension.
AB  - Reduced perfusion to the placenta in early pregnancy is believed to be the
      initiating factor in the development of preeclampsia, triggering local ischemia
      and systemic vascular hyperresponsiveness. This sequence of events creates a
      predisposition to the development of altered vascular function and hypertension.
      This study was designed to determine the influence of placental insufficiency on
      the responsiveness of mesenteric resistance arteries in an animal model of
      preeclampsia. Placental insufficiency was induced by reduction in uteroplacental
      perfusion pressure (RUPP) in experimental Sprague-Dawley rat dams. The uterine
      branches of the ovarian arteries and the abdominal aortae of pregnant rats were
      surgically constricted on gestational Day 14. Dams in the control group underwent
      a sham procedure. Rats were euthanized on gestational Day 20, followed by removal
      of the small intestine and adjacent mesentery. First-order mesenteric resistance
      arteries were mounted on a small vessel wire myograph and challenged with
      incremental concentrations of vasoconstrictors and vasorelaxants. Mesenteric
      arteries in dams with placental insufficiency demonstrated an increased maximal
      tension to phenylephrine (7.15 +/- 0.15 vs. 5.4 +/- 0.27 mN/mm, P < 0.001);
      potassium chloride at 60 mM (3.43 +/- 0.11 vs. 2.77 +/- 0.14 mN/mm, P < 0.01) and
      120 mM (3.92 +/- 0.18 vs. 2.97 +/- 0.16 mN/mm, P < 0.01); and angiotensin II
      (2.59 +/- 0.42 vs. 1.51 +/- 0.22 mN/mm, P < 0.05). Maximal relaxation to
      endothelium-dependent relaxants acetylcholine and calcium ionophore (A23187) was
      not significantly reduced. Data suggest that placental insufficiency leads to
      hyperresponsiveness to vasoconstrictor stimuli in mesenteric arteries.

PMID- 16946409
TI  - Hormonal changes accompanying cigarette smoke-induced preterm births in a mouse
      model.
AB  - Epidemiologic evidence indicates that maternal smoking increases the risk of
      preterm birth. While a number of plausible mechanisms for early delivery have
      been offered, the role of gestational hormones in this smoke-induced outcome is
      uncertain. Thus, a toxicologic study was performed to examine the effects and
      underlying hormonal mechanisms of mainstream cigarette smoke (MCS) exposure on
      gestational duration. Pregnant B6C3F1 mice were exposed by inhalation to MCS for
      5 days/week (4 hrs/day) from Gestational Day (GD) 4 to parturition. Smoke-induced
      effects on gestational length, interpubic ligament length, maternal hormone
      secretion patterns (estradiol-17beta, progesterone, prolactin, and relaxin), body
      weight gain, postimplantation loss, litter size, and offspring sex ratio were
      examined. Dams exposed to MCS at a concentration equivalent to smoking less than
      one pack of cigarettes/day (carbon monoxide = 25 parts per million, total
      suspended particulates = 16 mg/m3) demonstrated a significant (P < 0.05)
      shortening of gestational duration (compared with pregnant, air-exposed mice). In
      addition, MCS-exposed mice sacrificed on GD 18 had significantly (P < 0.05)
      increased interpubic ligament length, elevated serum estrogen levels, and a
      reduced progesterone to estradiol-17beta ratio (compared with air-exposed
      controls); levels of progesterone and prolactin were only modestly decreased and
      increased, respectively, in the MCS-exposed mice. Smoke exposure had no
      significant effects on maternal relaxin levels, body weight gain,
      postimplantation loss, litter size, or sex ratio. Results of this study
      demonstrate that inhalation exposure of pregnant mice to a low dose of MCS
      shortens gestation and alters hormone secretory patterns, which are important for
      maintaining pregnancy and inducing parturition. These findings support the view
      that pregnant women who smoke (even modestly) may be at increased risk for
      preterm birth, and that early delivery may be related (at least partly) to MCS
      induced.

PMID- 16946410
TI  - In situ cooling in a lung hilar clamping model of ischemia-reperfusion injury.
AB  - Experimental models for studying transplantation have up to now been unable to
      isolate reperfusion injury with minimal surgical manipulation and without the
      interference of graft rejection. Six pigs were subjected to left hilum
      preparation only (control group), and eight pigs were subjected to left hilum
      preparation plus in situ cooling ischemia and reperfusion of the lung
      (experimental group). The hilum was dissected free from other tissues in both
      groups. Lung preservation was achieved by antegrade flush perfusion via the left
      pulmonary artery. Pulmonary veins were clamped at the left atrium and a vent was
      created. The left main bronchus was clamped. Lung temperature was maintained at 4
      degrees -8 degrees C, while core temperature was kept at 38 degrees C. After 3
      hrs of cold ischemia the clamps were removed and the lung was reperfused.
      Elevated pulmonary vascular resistance and local and systemic aspects of ischemia
      reperfusion syndrome were consistently reproduced. This large-animal model of in
      situ unilateral lung cold ischemia with warm reperfusion proved to be very
      reliable in reproducing all aspects of ischemia-reperfusion injury. It excludes
      the interference of rejection and extensive surgical manipulation. We therefore
      propose its use in experimental studies investigating pharmaceutical or cooling
      modifications affecting lung ischemia-reperfusion outcomes.

PMID- 16946412
TI  - Biochemical and ultrastructural lung damage induced by rhabdomyolysis in the rat.
AB  - Rhabdomyolysis-induced oxidative stress is associated with morphological and
      functional damage to the kidney and other organs, but applications of this model
      in the lung are still lacking. The aim of the present study was to determine the
      relationship between oxidative stress and the morphological changes occurring in
      the lungs of rats subjected to rhabdomyolysis. Rhabdomyolysis was induced by
      intramuscular glycerol injection (50% v/v, 10 ml/kg), and the control group was
      injected with saline vehicle. Arterial blood samples were drawn at 0, 2, 4, and 6
      hrs for measurement of arterial gases, creatine kinase activity, and plasma free
      F2-isoprostane levels. Six hours later, the lungs were removed to determine the
      wet-to-dry weight ratio, reduced glutathione (GSH) and GSH disulfide (GSSG)
      levels, and activity of antioxidant enzymes (catalase [CAT], superoxide dismutase
      [SOD], and GSH peroxidase [GSH-Px]). Protein carbonylation and lipid peroxidation
      were assessed in the lungs by measurement of carbonyl and malondialdehyde (MDA)
      production, respectively. Bronchoalveolar lavage, cell counts, and lung
      ultrastructural studies were also performed. Six hours after glycerol injection,
      arterial PO2 and PCO2 were 23% and 38% lower, respectively, and plasma free F2
      isoprostane levels were 72% higher, compared with control values. In lungs,
      protein carbonyl and MDA production were 58% and 12% higher, respectively; the
      GSH:GSSG ratio and GSH-Px activity were 43% and 60% lower, respectively; and
      activities of CAT and SOD showed no significant differences compared with
      controls. Rhabdomyolysis-induced ultrastructural impairment of the lung showed
      Type II cell damage, extracytoplasmic lamellar bodies and lack of tubular myelin
      reorganization, endothelial cellular edema, and no disruption of the alveolar
      capillary barrier. These results provide evidence that rhabdomyolysis could
      induce tissue injury associated with increased oxidative stress, suggesting the
      contribution of oxidative stress to the pathogenic mechanism of acute lung
      injury.

PMID- 16946411
TI  - Inhibition of salivary secretion by activation of cannabinoid receptors.
AB  - It is known that marijuana use decreases saliva secretion. Therefore, we
      hypothesized that cannabinoid receptors (CBs) are located in salivary glands to
      mediate that effect. In these experiments, we used the submandibular gland (SMG)
      of male rats, which is one of the major salivary glands. Mammalian tissues
      contain at least two types of CBs, CB1 and CB2, mainly located in the nervous
      system and peripheral tissues, respectively. Both receptors are coupled to Gi
      protein and respond by inhibiting the activity of adenylyl cyclase. We
      demonstrated that both CB1 and CB2 are present in the SMG, each showing specific
      localizations. The best-known endocannabinoid is anandamide (AEA), which binds
      with high affinity to CB1 and CB2. We showed that AEA markedly reduced forskolin
      induced increase of cAMP content in vitro. This effect was blocked by AM251 and
      AM630 (CB1 and CB2 antagonists, respectively), indicating that both receptors are
      implicated in SMG physiology. In addition, we showed that AEA injected
      intraglandularly to anesthetized rats inhibited norepinephrine (NE)- and
      methacholine (MC)-stimulated saliva secretion in vivo and that both AM251 or
      AM630 prevented the inhibitory action of AEA. Also, the intraglandular injection
      of AM251 increased saliva secretion induced by lower doses of NE or MC. This
      increase was synergized after coinjection with AM630. Therefore, we concluded
      that AEA decreases saliva secretion in the SMG acting through CB1 and CB2
      receptors.

PMID- 16946413
TI  - Elevated bioactivity of the tolerogenic cytokines, interleukin-10 and
      transforming growth factor-beta, in the blood of acutely malnourished weanling
      mice.
AB  - The main objective of this investigation was to determine the influence of acute
      deficits of protein and energy on the blood levels of interleukin-10 (IL-10) and
      transforming growth factor-beta (TGF-beta), physiologically the main anti
      inflammatory and tolerogenic cytokines. In four 14-day experiments, male and
      female C57BL/6J mice, initially 19 days old, consumed a complete purified diet
      either ad libitum or in restricted daily quantities, or had free access to an
      isocaloric purified low-protein diet. A zero-time control group (19 days old) was
      included. In the first two experiments, serum IL-10 levels were assessed by
      sandwich enzyme-linked immunosorbent assay (ELISA) and bioassay. The mean serum
      IL-10 bioactivities were higher (P < or = 0.05) in both malnourished groups (low
      protein and restricted intake: 15.8 and 12.2 ng/ml, respectively) than in the
      zero-time and age-matched control groups (6.3 and 7.3 ng/ml, respectively),
      whereas serum IL-10 immunoactivity was high only in the restricted intake group
      (e.g., second experiment: 17.0 pg/ml vs. 5.4, 3.7, and 3.1 pg/ml in the zero-time
      control, age-matched control and low-protein group, respectively). The third and
      fourth experiments centered on plasma TGF-beta immunoactivity (sandwich ELISA)
      and bioactivity, respectively. The ELISA revealed a high mean plasma TGF-beta1
      level (P < or = 0.05) in the low-protein group only, but TGF-beta bioactivity
      (beta1 isoform, although 15% beta2 in the restricted intake group) was high in
      both malnourished groups (8.7 and 9.3 ng/ml in the low-protein and restricted
      groups, respectively) relative to the age-matched control group (0.5 ng/ml).
      Thus, metabolically distinct weanling systems mimicking marasmus and incipient
      kwashiorkor both exhibit a blood cytokine profile that points to a tolerogenic
      microenvironment within immune response compartments. A model emerges in which
      malnutrition-associated immune competence, at least in advanced weight loss,
      centers on cytokine-mediated peripheral tolerance that reduces the risk of
      catabolically induced autoimmune disease, but this is at the cost of attenuated
      responsiveness to infectious agents.

PMID- 16946414
TI  - Systems biology approaches to metabolic and cardiovascular disorders: network
      perspectives of cardiovascular metabolism.
AB  - In this review, we examine cardiovascular metabolism from three different, but
      highly complementary, perspectives. First, from the abstract perspective of a
      metabolite network, composed of nodes and links. We present fundamental concepts
      in network theory, including emergence, to illustrate how nature has designed
      metabolism with a hierarchal modular scale-free topology to provide a robust
      system of energy delivery. Second, from the physical perspective of a modular
      spatially compartmentalized network. We review evidence that cardiovascular
      metabolism is functionally compartmentalized, such that oxidative
      phosphorylation, glycolysis, and glycogenolysis preferentially channel ATP to
      ATPases in different cellular compartments, using creatine kinase and adenylate
      kinase to maximize efficient energy delivery. Third, from the dynamics
      perspective, as a network of dynamically interactive metabolic modules capable of
      self-oscillation. Whereas normally, cardiac metabolism exists in a regime in
      which excitation-metabolism coupling closely matches energy supply and demand, we
      describe how under stressful conditions, the network can be pushed into a
      qualitatively new dynamic regime, manifested as cell-wide oscillations in ATP
      levels, in which the coordination between energy supply and demand is lost. We
      speculate how this state of "metabolic fibrillation" leads to cell death if not
      corrected and discuss the implications for cardioprotection.

PMID- 16946415
TI  - Chronic diseases: transmittable pathogens and cultural traits.

PMID- 16946416
TI  - Nutrition and dental medicine: where is the connection?

PMID- 16946417
TI  - A message from the division of science.

PMID- 16946418
TI  - Ethical question.

PMID- 16946420
TI  - Depending on vaccines.

PMID- 16946419
TI  - Mineral trioxide aggregate.

PMID- 16946421
TI  - Dental education.

PMID- 16946422
TI  - Business training.

PMID- 16946423
TI  - More on education.

PMID- 16946427
TI  - Assessing patients' caries risk.
AB  - BACKGROUND: Caries management historically has focused on the removal of
      cavitated carious tissue and restoration of the tooth. OVERVIEW: Assessing a
      patient's risk of developing caries is a vital component of caries management. A
      comprehensive caries assessment should consider factors such as past and current
      caries experience, diet, fluoride exposure, presence of cariogenic bacteria,
      salivary status, general medical history, behavioral and physical factors, and
      medical and demographic characteristics that may affect caries development. A
      caries risk assessment also should consider factors that may challenge the
      patient's ability to maintain good oral hygiene (for example, crowded dentition,
      deep fissures, wide open restorative margins or placement of oral appliances).
      CONCLUSIONS: and Practical Implications. The authors review the importance of
      caries risk assessment as a prerequisite for appropriate preventive and treatment
      intervention decisions and provide some practical information on how general
      practitioners can incorporate caries risk assessment into the management of
      caries.

PMID- 16946428
TI  - Alzheimer's disease: psychopathology, medical management and dental implications.
AB  - BACKGROUND: The authors review the clinical features, epidemiology,
      pathophysiology, medical management, dental findings and dental treatment of
      patients with Alzheimer's disease (AD). STUDIES REVIEWED: The authors conducted
      MEDLINE searches for 2000 through 2005 using the terms "Alzheimer's disease,"
      "geriatric," "epidemiology," "pathophysiology," "treatment" and "dentistry."
      Reports selected for further review included those published in English in peer
      reviewed journals. The authors gave preference to articles reporting randomized,
      controlled trials. RESULTS: AD is a progressive and fatal neurodegenerative
      disorder characterized by cognitive dysfunctions, particularly in learning and
      memory, and the emergence of behavioral abnormalities. Deficiencies in the cells
      responsible for storage and processing of information underlie the cognitive,
      functional and behavioral changes seen in patients with the disorder. CLINICAL
      IMPLICATIONS: As the elderly population grows, increasing numbers of Americans
      with AD will require dental treatment. The prevalence of dental disease likely
      will be extensive, because of diminished salivary flow and patients' inability to
      perform appropriate oral hygiene techniques. Preventive dental education for the
      caregiver and use of saliva substitutes and anticaries agents by the patient are
      indicated.

PMID- 16946429
TI  - An evaluation of search and selection methods used in dental systematic reviews
      published in English.
AB  - BACKGROUND: Increasing numbers of systematic reviews are published each year,
      though little has been done to evaluate their search and selection methodology.
      METHODS: The authors searched dental systematic reviews published between Jan. 1,
      2000, and July 14, 2005, for descriptions of how researchers used multiple
      electronic databases and secondary searches. They evaluated search and selection
      methods of identified systematic reviews against the guidelines found in the 2005
      Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: The authors
      identified 220 unique dental systematic reviews. They found that all aspects of
      search and selection methodology had improved. In 2005, most systematic reviews
      documented database names and search dates (90 percent), electronic search terms
      (95 percent) and inclusion-exclusion criteria (95 percent), and most employed
      secondary searching (100 percent). Many still failed to search more than MEDLINE
      (20 percent), document the search strategy (20 percent), use multiple reviewers
      for selecting studies (25 percent) and include all languages (39 percent).
      CONCLUSIONS AND CLINICAL IMPLICATIONS: Systematic review methodology is
      improving, though key components frequently are absent. Reviews should be read
      critically and in consideration of the methodological flaws.

PMID- 16946430
TI  - Translating the new dietary guidelines.
AB  - BACKGROUND: Diet- and nutrition-related diseases influence oral health. The U.S.
      government recently revisited the dietary guidelines for health promotion and
      chronic disease prevention. The purpose of this article is to review the new
      recommendations. CONCLUSIONS: The Dietary Reference Intakes are designed to
      identify nutrient intakes required to maintain health in people of a given age
      and sex. The Dietary Guidelines for Americans are designed to promote healthy
      dietary and activity habits. MyPyramid is designed to identify individual dietary
      patterns to ensure adequate nutrient intakes within energy needs. CLINICAL
      IMPLICATIONS: Familiarization with the new dietary guidelines will enable dental
      practitioners to develop diet-related oral health recommendations that are
      consistent with disease prevention.

PMID- 16946431
TI  - A comparison of the efficacy of Er,Cr:YSGG laser and rotary instrumention in root
      canal debridement.
AB  - BACKGROUND: The authors evaluated the efficacy of an erbium,chromium:
      yttrium,scandium,gallium,garnet (Er,Cr:YSGG) laser-powered hydrokinetic system
      (HKS) versus that of rotary instrumentation for root canal debridement. METHODS:
      The authors studied four uninstrumented controls and two test groups of 18
      matched pairs of teeth. Teeth from each pair underwent different instrumentation
      but received identical irrigation solutions. The instrumentation protocol
      involved either rotary instrumentation or the Er,Cr:YSGG laser. The irrigation
      groups received 0.5 milliliter of distilled water or 5.25 percent sodium
      hypochlorite (NaOCl) between instruments. The authors measured the amount of
      debris remaining at 2 and 4 mm from the apex as a percentage of total lumen area.
      RESULTS: Lased canals had significantly more debris than did canals that received
      rotary instrumentation (Wilcoxon signed rank test, P < .001). With distilled
      water irrigation, the debris remaining in lased canals at both the 2-and 4-mm
      levels was not statistically different from that remaining in uninstrumented
      controls. Rotary instrumentation yielded significantly less remaining debris than
      did laser instrumentation (Wilcoxon signed rank test, P < .001). With 5.25
      percent NaOCl irrigation, there was no difference in remaining debris between the
      two groups (Wilcoxon signed rank test , P < .001). The lased group received
      significantly more irrigant than did the rotary group (Wilcoxon rank sum test, P
      < .001). CONCLUSIONS: This study indicates that the debridement efficacy of the
      HKS with distilled water irrigation is unacceptable; with 5.25 percent NaOCl
      irrigation, it is similar to that of rotary instrumentation. CLINICAL
      IMPLICATIONS: If the HKS is to be used for debridement, then NaOCl irrigation
      must be used for predictable tissue removal.

PMID- 16946432
TI  - Headache impact in patients with orofacial pain.
AB  - BACKGROUND: The authors conducted a cross-sectional survey to assess headache
      disability in patients with orofacial pain. METHODS: The authors administered a
      Migraine Disability Assessment (MIDAS) questionnaire to 337 university-based
      clinic patients with OFP and 367 general dental (GD) patients, who served as
      controls. They made primary and secondary diagnoses in patients with OFP
      according to standard diagnostic criteria. The authors classified the patients
      into three major categories: primary headache (PH), musculoskeletal disorders
      (MS) and neuropathic pain (NP). They categorized the MIDAS score into four
      severity grades (I, the lowest, through IV, the highest). The authors analyzed
      the data using chi(2), t test, one-way analysis of variance and logistic
      regression for calculated odds ratios. RESULTS: Patients with OFP had a greater
      prevalence of headache than did patients in the GD group (72.7 percent versus
      31.9 percent, respectively; P < .001), with a higher total MIDAS score, number of
      headache days in the previous three months and headache severity (P < .001).
      Within the OFP group, the diagnostic prevalence of PH, MS and NP was 7.1 percent,
      79.8 percent and 13.1 percent, respectively (P < .001). The authors categorized
      56 percent of patients with OFP and headache into the high-impact headache group
      (MIDAS grades III and IV; P < .001). CONCLUSIONS: Patients with OFP had a higher
      prevalence of headache with greater disability impact than did control subjects.
      The degree of disability was related strongly to the MS diagnosis. CLINICAL
      IMPLICATIONS: The coexistence of PH and MS disorders can lead to higher headache
      disability. Clinicians need to treat both disorders concomitantly, which will
      result in improved treatment outcomes.

PMID- 16946433
TI  - Internal contamination of air-driven low-speed handpieces and attached prophy
      angles.
AB  - BACKGROUND: In an in vitro crossover study, the authors investigated whether the
      interior of low-speed handpiece/prophy-angle systems becomes contaminated during
      operation and submersion into Geobacillus stearothermophilus. METHODS: This study
      involved two types of handpieces attached to eight brands of prophy angles. The
      researchers operated angles attached to sterile handpieces for 60 seconds. They
      then analyzed the inside surfaces of the angle, nosecone and motor. They tested
      each prophy angle and handpiece 10 times. RESULTS: In the 160 tests of handpieces
      contaminated at the prophy cup end, the spores traveled into the motor gears 32
      times (20 percent). In the other 160 tests in which the motor gears were
      contaminated, the test bacterium traveled through the prophy cup in 75 instances
      (47 percent). CONCLUSIONS: The in vitro data suggest that low-speed handpiece
      motors can become contaminated internally during use with prophy angles. Also,
      internal contaminants appear to have been released from the handpiece. CLINICAL
      IMPLICATIONS: The results suggest that low-speed hand-pieces can become
      contaminated internally during use. Unless low-speed handpieces are sterilized
      properly between patients, they may become cross-contaminated.

PMID- 16946434
TI  - 'Research is in my blood': Dr. Lorne Golub, developer of Periostat, receives the
      ADA's Gold Medal Award for Excellence in Dental Research.

PMID- 16946435
TI  - From production to performance: solving the positioning dilemma in dental
      practice.
AB  - BACKGROUND: Thriving dental practices are excellent at providing a warm personal
      experience or are efficient, fast and cost-effective. Those that that attempt to
      do both end up being mediocre at just about everything. CONCLUSIONS: Introducing
      ideas from dramaturgy and service simultaneity in the services marketing
      literature, the authors provide a model for the conceptualization and redesign of
      the dental practice. PRACTICE IMPLICATIONS: Successful dental practices will be
      those that concentrate on low customization of activities in the back office or
      high customization of activities in the front office.

PMID- 16946436
TI  - Computer-aided design and fabrication of dental restorations: current systems and
      future possibilities.
AB  - BACKGROUND: For more than 20 years, researchers have been trying to automate
      conventional manual processes in dental technology with the hope of producing
      higher- and more uniform-quality materials, standardizing manufacturing processes
      and reducing production costs. METHODS: The authors review existing computer
      aided design (CAD)/computer-aided manufacturing (CAM) systems, describing the
      components of CAD/CAM technologies and addressing the limitations of current
      systems, and suggest possibilities for future systems. CONCLUSIONS: Existing
      dental CAD/CAM systems vary dramatically in their capabilities; each has distinct
      advantages and limitations. None can yet acquire data directly in the mouth and
      produce the full spectrum of restoration types (with the breadth of material
      choices) that can be created by traditional techniques. Emerging technologies may
      expand dramatically the capabilities of future systems, but they also may require
      a different type of training to use them to their full effectiveness. CLINICAL
      IMPLICATIONS: In the future, automatically fabricated, fully esthetic
      restorations might be produced more quickly and have longer lifetimes than
      restorations currently produced with CAD/CAM systems.

PMID- 16946437
TI  - Is the wide range in crown fees justifiable?

PMID- 16946438
TI  - What hinders true potential?

PMID- 16946439
TI  - Should a dentist disclose that he is paying for the publication of his newspaper
      column?

PMID- 16946440
TI  - The use of dental radiographs: update and recommendations.
AB  - BACKGROUND AND OVERVIEW: The National Council on Radiation Protection &
      Measurements updated its recommendations on radiation protection in dentistry in
      2003, the Centers for Disease Control and Prevention published its Guidelines for
      Infection Control in Dental Health-Care Settings in 2003, and the U.S. Food and
      Drug Administration updated its selection criteria for dental radiographs in
      2004. This report summarizes the recommendations presented in these documents and
      addresses additional topics such as patient selection criteria, film selection
      for conventional radiographs, collimation, beam filtration, patient protective
      equipment, film holders, operator protection, film exposure and processing,
      infection control, quality assurance, image viewing, direct digital radiography
      and continuing education of dental health care workers who expose radiographs.
      CONCLUSIONS: This report discusses implementation of proper radiographic
      practices. In addition to these guidelines, dentists should be aware of, and
      comply with, applicable federal and state regulations. CLINICAL IMPLICATIONS:
      Dentists should weigh the benefits of dental radiographs against the consequences
      of increasing a patient's exposure to radiation and implement appropriate
      radiation control procedures.

PMID- 16946441
TI  - Dietary guidelines for Americans and MyPyramid.

PMID- 16946442
TI  - Antidote use in the critically ill poisoned patient.
AB  - The proper use of antidotes in the intensive care setting when combined with
      appropriate general supportive care may reduce the morbidity and mortality
      associated with severe poisonings. The more commonly used antidotes that may be
      encountered in the intensive care unit (N-acetylcysteine, ethanol, fomepizole,
      physostigmine, naloxone, flumazenil, sodium bicarbonate, octreotide, pyridoxine,
      cyanide antidote kit, pralidoxime, atropine, digoxin immune Fab, glucagon,
      calcium gluconate and chloride, deferoxamine, phytonadione, botulism antitoxin,
      methylene blue, and Crotaline snake antivenom) are reviewed. Proper indications
      for their use and knowledge of the possible adverse effects accompanying
      antidotal therapy will allow the physician to appropriately manage the severely
      poisoned patient.

PMID- 16946443
TI  - Critical care of the obstetric patient.
AB  - The obstetric patient poses exceptional challenges in the intensive care unit.
      Knowledge of the physiologic changes of pregnancy and specific pregnancy-related
      disorders is necessary for optimal management. Intensive care unit diagnoses may
      include preeclampsia, including the HELLP syndrome, pulmonary embolic disease,
      amniotic fluid embolism, status asthmaticus, respiratory infection, the acute
      respiratory distress syndrome, and sepsis. The management of mechanical
      ventilation is based on principles of avoiding lung injury, and hypercapnia may
      be tolerated even during the pregnancy. When the clinician is faced with the
      extraordinary instance of cardiopulmonary arrest, perimortem cesarean delivery
      must be considered to improve the potential for maternal and fetal survival.

PMID- 16946444
TI  - Obesity and sepsis.
AB  - Obesity has reached epidemic proportions over the last few decades. Obesity is
      associated with increased morbidity and mortality in hypertension, cardiovascular
      diseases, stroke, and cancer and is feared to decrease overall life expectancy
      over the next few decades. There is a growing body of evidence suggesting that
      obesity is a chronic inflammatory disease. Obesity is becoming a cause of concern
      in critically ill patients as well. Sepsis is the number one cause of morbidity
      and mortality in noncoronary artery disease critical care units all over the
      world and is associated with a high cost of care. An increase in morbidity in
      obese septic patients compared with lean people is a cause of growing concern.
      Laboratory evidence suggests that there is exaggeration in the inflammatory and
      prothrombogenic phenotype assumed by obese compared with lean septic animals. The
      exact mechanisms underlying this phenomenon are unknown. This article reviews
      some of the pathophysiological processes responsible for the underlying
      inflammation in obesity and sepsis and reviews the literature for the association
      of the two.

PMID- 16946445
TI  - Nonoperative management of spleen and liver injuries.
AB  - The spleen and liver are the 2 most commonly injured abdominal organs following
      trauma. Trends in management have changed over the years, and the majority of
      these injuries are now managed nonoperatively. Splenic injuries can be managed
      via simple observation or with angiography and embolization. Recent data suggest
      that there are few true contraindications in the setting of hemodynamic
      stability. Success rate of nonoperative management may be as high as 95%. Liver
      injuries can be approached similarly. In the setting of a hemodynamically stable
      patient, observation with or without angiography and embolization may similarly
      be used. As many as 80% of patients with liver injury can be successfully managed
      without laparotomy. This review will discuss current concepts in nonoperative
      management of liver and spleen, including diagnosis, patient selection,
      nonoperative management strategies, benefits, risks, and complications.

PMID- 16946446
TI  - Acute therapy of maternal and fetal arrhythmias during pregnancy.
AB  - Atrial premature beats are frequently diagnosed during pregnancy.
      Supraventricular tachycardia (atrial tachycardia, atrioventricular nodal
      reentrant tachycardia, circus movement tachycardia) is diagnosed less frequently.
      For acute therapy, electrical cardioversion with 50 to 100 J is indicated in all
      unstable patients. In stable supraventricular tachycardia, the initial therapy
      includes vagal maneuvers to terminate tachycardias. For short-term management,
      when vagal maneuvers fail, intravenous adenosine is the first choice drug and may
      safely terminate the arrhythmia. Ventricular premature beats are also frequently
      present during pregnancy and are benign in most patients; however, malignant
      ventricular tachyarrhythmias (sustained ventricular tachycardia, ventricular
      flutter, or ventricular fibrillation) may occur. Electrical cardioversion is
      necessary in all patients who are hemodynamically unstable with life-threatening
      ventricular tachyarrhythmias. In hemodynamically stable patients, initial therapy
      with ajmaline, procainamide, or lidocaine is indicated. In patients with syncopal
      ventricular tachycardia, ventricular fibrillation, ventricular flutter, or
      aborted sudden death, an implantable cardioverter-defibrillator is indicated. In
      patients with symptomatic bradycardia, a pacemaker can be implanted using
      echocardiography at any stage of pregnancy. The treatment of the pregnant patient
      with cardiac arrhythmias requires important modifications of the standard
      practice of arrhythmia management. The goal of therapy is to protect the patient
      and fetus through delivery, after which chronic or definitive therapy can be
      administered.

PMID- 16946447
TI  - Posttraumatic stress disorder in the child of an adult burn victim: a case report
      and review of the literature.
AB  - Adults with a myriad of medical and surgical conditions are at risk for pain,
      delirium, and disfigurement. Needless to say, these critical illnesses are
      profoundly stressful for patients and their caregivers. However, physicians
      rarely consider the reactions of children to their parents' illnesses. The
      article presents the case of a 15-year-old girl who developed posttraumatic
      stress disorder following her mother's severe burn and complicated course in a
      critical care unit; the case is used to discuss strategies for the detection of
      psychological vulnerability and for the implementation of care. By learning more
      about the children of adult patients, by screening for interpersonal dysfunction,
      and by maximizing support systems, clinicians can improve function and minimize
      distress.

PMID- 16946448
TI  - Combinations of SPR and MS for characterization of native and recombinant
      proteins in cell lysates.
AB  - Surface plasmon resonance and mass spectrometry (SPR-MS) has been combined for
      quality check of recombinant 6xHis-tagged 14-3-3 proteins expressed in
      Escherichia coli. Lysates were injected over an SPR sensorchip with immobilized
      Ni2+ for SPR analysis of the specific Ni2+ binding response and stability. To
      validate the identity, intactness and homogeneity of the captured proteins were
      eluted for mass spectrometric analysis of intact molecular weight and peptide
      mass mapping. Additionally, the captured recombinant proteins were investigated
      for specific binding to known phosphorylated ligands of 14-3-3 proteins in order
      to test their activity. Specific binding of recombinant and native 14-3-3
      proteins in complex mixtures to immobilized phosphopeptides and subsequent
      elution was also tested by SPR-MS. Ammonium sulfate precipitate fractions from
      lysates of E. coli expressing 14-3-3 protein and of cauliflower were investigated
      for specific binding to the phosphopeptide ligands immobilized on a sensorchip by
      SPR. Subsequently, the bound protein was eluted and analyzed by MS for
      characterization of intact mass and peptide mass mapping.

PMID- 16946449
TI  - Evidence of DNA rearrangements in the 128-kilobase pBtoxis plasmid of Bacillus
      thuringiensis israelensis.
AB  - BUPM97 is a novel Tunisian isolate of Bacillus thuringiensis israelensis
      presenting insecticidal activity against Culex pipiens larvae. The delta
      endotoxins pattern of this strain was different from that of the reference strain
      B. thuringiensis israelensis H14. Therefore, the study of its cry genes content
      was carried out by restriction-fragment-length-polymorphism (RFLP) using specific
      cry genes probes and by DNA sequencing. It was clearly demonstrated that in the
      strain BUPM97 the cry4A and cry10A genes were deleted from the B. thuringiensis
      israelensis 128-kb pBtoxis plasmid. In addition, a strong DNA sequence
      polymorphism was evidenced in the same plasmid downstream from the cry4B gene.
      This very particular DNA dynamic evidenced in this new strain of B. thuringiensis
      israelensis should be taken into consideration, regarding the strain stability
      during the industrial production of B. thuringiensis bioinsecticides.

PMID- 16946450
TI  - Effects of E. coli chaperones on the solubility of human receptors in an in vitro
      expression system.
AB  - The implementation of efficient technologies for the production of recombinant
      mammalian membrane receptors is an outstanding challenge in understanding
      receptor-ligand actions and the development of therapeutic antibodies. In order
      to improve the solubility of recombinant extracellular domains of human membrane
      receptors expressed in Escherichia coli, proteins were synthesized by an E. coli
      in vitro translation system supplemented with bacterial molecular chaperones,
      such as GroEL-GroES (GroEL/ES), Trigger factor (TF), a DnaK-DnaJ-GrpE chaperone
      system (DnaKJE), and/or a heat shock protein Hsp100, ClpB. The following three
      proteins that are prone to aggregation were examined: the extracellular domain
      (ECD) or the second immunoglobulin-like domain (IgII) of the human neurotrophin
      receptor TrkC (TrkC-ECD and TrkC-IgII), and the C-type lectin carbohydrate
      recognition domain of the human asialoglycoprotein receptor (ASGPR HI CRD). The
      cooperative chaperone system including GroEL/ES, DnaKJE and ClpB had a marked
      effect on the solubility of TrkC-ECD and TrkC-IgII, and the GroEL/ES-DnaKJE-TF
      chaperone system was more effective for TrkC-IgII. The GroEL/ES-DnaKJE-TF
      chaperone network increased the yield of soluble ASGPR HI CRD. The present
      findings demonstrate that E. coli molecular chaperones are useful in improving
      the yield of soluble recombinant extracellular domains of human membrane
      receptors in an E. coli expression system.

PMID- 16946451
TI  - Improvement of the lytic properties of a beta-1,3-glucanase by directed
      evolution.
AB  - BGLII is a bacterial endoglucanase that hydrolyzes the beta-1,3-glucan present in
      yeast cell walls, resulting in lysis of Saccharomyces cerevisiae. As a result of
      this property, BGLII is considered a potential tool for downstream processing and
      recovery of biotechnological products produced in yeast. Here we describe the
      improvement of the yeast lytic activity of BGLII, achieved by a directed
      evolution approach involving random mutagenesis and screening for variants with
      improved catalytic activity, combined with site-directed mutagenesis. A BGLII
      variant having three times the wild-type hydrolytic activity on laminarin was
      identified. The purified enzyme also exhibited higher lytic activity on yeast
      cells. Mutations causing the improvements are located very close to each other in
      the amino acid sequence, suggesting that the region should be considered as a
      target for further improvements of the glucanase activity. These results
      demonstrate the feasibility of molecular evolution methods for the improvement of
      the BGLII hydrolytic activity, and open a window for further improvement of this
      or other properties in glycosyl hydrolases in general.

PMID- 16946453
TI  - Methods and protocols of modern solid phase Peptide synthesis.
AB  - The purpose of this article is to delineate strategic considerations and provide
      practical procedures to enable non-experts to synthesize peptides with a
      reasonable chance of success. This article is not encyclopedic but rather devoted
      to the Fmoc/tBu approach of solid phase peptide synthesis (SPPS), which is now
      the most commonly used methodology for the production of peptides. The principles
      of SPPS with a review of linkers and supports currently employed are presented.
      Basic concepts for the different steps of SPPS such as anchoring, deprotection,
      coupling reaction and cleavage are all discussed along with the possible problem
      of aggregation and side-reactions. Essential protocols for the synthesis of fully
      deprotected peptides are presented including resin handling, coupling, capping,
      Fmoc-deprotection, final cleavage and disulfide bridge formation.

PMID- 16946452
TI  - Antisense therapy in clinical oncology: preclinical and clinical experiences.
AB  - Nucleic acid molecules have emerged as versatile tools with promising utility as
      therapeutics for human diseases. The specificity of hybridization of an antisense
      oligonucleotide (AS ODN) to the target mRNA makes the AS strategy attractive to
      selectively modulate the expression of genes involved in the pathogenesis of
      malignant or non-malignant diseases. One AS drug has been approved for local
      therapy of cytomegalovirus retinitis, and a number of AS ODN are currently tested
      in clinical trials including ODN that target bcl-2, survivin, and DNA
      methyltransferase. The clinical studies indicate that AS ODN are well tolerated
      and may have therapeutic activity. In this overview, we summarize therapeutic
      concepts, clinical studies, and new promising molecular targets to treat human
      cancer with AS ODN.

PMID- 16946454
TI  - Current concepts in antiretroviral therapy failure.
AB  - Currently, the goal for the first and second, possibly the third, antiretroviral
      regimen is the suppression of HIV replication to plasma levels below assay
      detection (ie, <50 HIV-1 RNA copies/mL). In patients with advanced treatment
      failure and resistance to numerous drugs, the goal of therapy has been to reduce
      viral load as much as possible and to maintain immunologic and clinical
      integrity. With the recent availability of new drugs and new classes of drugs,
      complete suppression of viral replication may be possible even in late salvage.
      When designing a regimen for a patient for whom antiretroviral therapy has
      failed, the regimen should contain at least 3 active drugs, and regimens are best
      selected with assistance from genotypic and phenotypic drug resistance testing.
      The selection should also be guided by knowledge of potential pharmacokinetic
      interactions among drugs. This article summarizes a presentation on
      antiretroviral failure by Carlos del Rio, MD, at the 8th Annual clinical meeting
      for Ryan White CARE Act clinicians in New Orleans in June 2005, sponsored by the
      International AIDS Society-USA and includes more recent data presented at the
      13th Conference on Retroviruses and Opportunistic Infections (CROI) in 2006.

PMID- 16946455
TI  - Structured treatment interruptions--new findings.
AB  - A number of recent studies have examined structured treatment interruption (STI)
      of antiretroviral therapy using CD4+ cell count-guided or time-based strategies
      in patients with chronic HIV infection and stable suppression of HIV RNA. On
      balance, data from these studies indicate that STI is associated with worse
      immunologic, virologic, and clinical outcomes than continuous antiretroviral
      therapy. However, the potential may still exist for use of short-term STI to
      manage drug toxicities in patients in this setting or to assess immunologic and
      virologic outcomes of novel interventions in carefully controlled clinical
      trials. This article summarizes a presentation on STI made by Constance A.
      Benson, MD, at the International AIDS Society-USA course in San Francisco in
      April 2006.

PMID- 16946456
TI  - Review of treatment studies of depression in HIV.
AB  - Depression is a prevalent and interfering, yet potentially treatable illness
      commonly comorbid with HIV/AIDS. In HIV, symptoms and diagnoses of depression
      have been associated with poor adherence to antiretroviral medication regimens
      and to accelerated disease progression. This article is a review of the existing
      literature on the treatment of depression in the context of HIV, including: (1)
      psychosocial and behavioral health interventions that directly target Diagnostic
      and Statistical Manual of Mental Disorders (DSM) unipolar depressive disorders,
      (2) psychosocial interventions that indirectly target depressive symptoms, and
      (3) psychopharmacologic treatment studies for DSM-IV unipolar depressive
      disorders. Psychosocial and psychopharmacologic treatments of depression appear
      to be effective for individuals with HIV. However, additional methodologically
      rigorous trials are needed for definitive inferences regarding treatment
      efficacy. Because of the high frequency of depression comorbid with HIV, and the
      association of depression with important self-care behaviors in this population,
      identification of efficacious treatments for depression has the potential to
      improve both overall quality of life and, potentially, health outcomes.

PMID- 16946457
TI  - Update of the drug resistance mutations in HIV-1: Fall 2006.
AB  - The International AIDS Society-USA (IAS-USA) Drug Resistance Mutations Group is
      marking 6 years as an independent volunteer panel of experts focused on
      identifying key HIV-1 drug resistance mutations. The goal of the effort is to
      quickly deliver accurate and unbiased information on these mutations to HIV
      clinical practitioners. This version of the IAS-USA Drug Resistance Mutations
      Figures replaces the version published in this journal in October/November 2005.
      The IAS-USA Drug Resistance Mutations Figures are designed for use in identifying
      mutations associated with viral resistance to antiretroviral drugs and in making
      therapeutic decisions. Care should be taken when using this list of mutations for
      surveillance or epidemiologic studies of transmission of drug-resistant virus. A
      number of amino acid substitutions, particularly minor mutations, represent
      polymorphisms that in isolation may not reflect prior drug selective pressure or
      reduced drug susceptibility.

PMID- 16946458
TI  - Trypanosoma brucei UDP-galactose-4'-epimerase in ternary complex with NAD+ and
      the substrate analogue UDP-4-deoxy-4-fluoro-alpha-D-galactose.
AB  - The structure of the NAD-dependent oxidoreductase UDP-galactose-4'-epimerase from
      Trypanosoma brucei in complex with cofactor and the substrate analogue UDP-4
      deoxy-4-fluoro-alpha-D-galactose has been determined using diffraction data to
      2.7 A resolution. Despite the high level of sequence and structure conservation
      between the trypanosomatid enzyme and those from humans, yeast and bacteria, the
      binding of the 4-fluoro-alpha-D-galactose moiety is distinct from previously
      reported structures. Of particular note is the observation that when bound to the
      T. brucei enzyme, the galactose moiety of this fluoro-derivative is rotated
      approximately 180 degrees with respect to the orientation of the hexose component
      of UDP-glucose when in complex with the human enzyme. The architecture of the
      catalytic centre is designed to effectively bind different orientations of the
      hexose, a finding that is consistent with a mechanism that requires the sugar to
      maintain a degree of flexibility within the active site.

PMID- 16946459
TI  - Structure of anti-FLAG M2 Fab domain and its use in the stabilization of
      engineered membrane proteins.
AB  - The inherent difficulties of stabilizing detergent-solubilized integral membrane
      proteins for biophysical or structural analysis demand the development of new
      methodologies to improve success rates. One proven strategy is the use of
      antibody fragments to increase the ;soluble' portion of any membrane protein, but
      this approach is limited by the difficulties and expense associated with
      producing monoclonal antibodies to an appropriate exposed epitope on the target
      protein. Here, the stabilization of a detergent-solubilized K(+) channel protein,
      KvPae, by engineering a FLAG-binding epitope into a known loop region of the
      protein and creating a complex with Fab fragments from commercially available
      anti-FLAG M2 monoclonal antibodies is reported. Although well diffracting
      crystals of the complex have not yet been obtained, during the course of
      crystallization trials the structure of the anti-FLAG M2 Fab domain was solved to
      1.86 A resolution. This structure, which should aid future structure
      determination efforts using this approach by facilitating molecular-replacement
      phasing, reveals that the binding pocket appears to be specific only for the
      first four amino acids of the traditional FLAG epitope, namely DYKD. Thus, the
      use of antibody fragments for improving the stability of target proteins can be
      rapidly applied to the study of membrane-protein structure by placing the short
      DKYD motif within a predicted peripheral loop of that protein and utilizing
      commercially available anti-FLAG M2 antibody fragments.

PMID- 16946460
TI  - Structure of the Y94F mutant of Escherichia coli thymidylate synthase.
AB  - Tyr94 of Escherichia coli thymidylate synthase is thought to be involved, either
      directly or by activation of a water molecule, in the abstraction of a proton
      from C5 of the 2'-deoxyuridine 5'-monophosphate (dUMP) substrate. Mutation of
      Tyr94 leads to a 400-fold loss in catalytic activity. The structure of the Y94F
      mutant has been determined in the native state and as a ternary complex with
      thymidine 5'-monophosphate (dTMP) and 10-propargyl 5,8-dideazafolate (PDDF).
      There are no structural changes ascribable to the mutation other than loss of a
      water molecule hydrogen bonded to the tyrosine OH, which is consistent with a
      catalytic role for the phenolic OH.

PMID- 16946462
TI  - Structure of Bacillus halmapalus alpha-amylase crystallized with and without the
      substrate analogue acarbose and maltose.
AB  - Recombinant Bacillus halmapalus alpha-amylase (BHA) was studied in two different
      crystal forms. The first crystal form was obtained by crystallization of BHA at
      room temperature in the presence of acarbose and maltose; data were collected at
      cryogenic temperature to a resolution of 1.9 A. It was found that the crystal
      belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 47.0, b =
      73.5, c = 151.1 A. A maltose molecule was observed and found to bind to BHA and
      previous reports of the binding of a nonasaccharide were confirmed. The second
      crystal form was obtained by pH-induced crystallization of BHA in a MES-HEPES
      boric acid buffer (MHB buffer) at 303 K; the solubility of BHA in MHB has a
      retrograde temperature dependency and crystallization of BHA was only possible by
      raising the temperature to at least 298 K. Data were collected at cryogenic
      temperature to a resolution of 2.0 A. The crystal belonged to space group
      P2(1)2(1)2(1), with unit-cell parameters a = 38.6, b = 59.0, c = 209.8 A. The
      structure was solved using molecular replacement. The maltose-binding site is
      described and the two structures are compared. No significant changes were seen
      in the structure upon binding of the substrates.

PMID- 16946461
TI  - Structure of the SH3 domain of human osteoclast-stimulating factor at atomic
      resolution.
AB  - Osteoclast-stimulating factor (OSF) is an intracellular signaling protein,
      produced by osteoclasts themselves, that enhances osteoclast formation and bone
      resorption. It is thought to act via an Src-related signaling pathway and
      contains SH3 and ankyrin-repeat domains which are involved in protein-protein
      interactions. As part of a structure-based anti-bone-loss drug-design program,
      the atomic resolution X-ray structure of the recombinant human OSF SH3 domain
      (hOSF-SH3) has been determined. The domain, residues 12-72, yielded crystals that
      diffracted to the ultrahigh resolution of 1.07 A. The overall structure shows a
      characteristic SH3 fold consisting of two perpendicular beta-sheets that form a
      beta-barrel. Structure-based sequence alignment reveals that the putative proline
      rich peptide-binding site of hOSF-SH3 consists of (i) residues that are highly
      conserved in the SH3-domain family, including residues Tyr21, Phe23, Trp49,
      Pro62, Asn64 and Tyr65, and (ii) residues that are less conserved and/or even
      specific to hOSF, including Thr22, Arg26, Thr27, Glu30, Asp46, Thr47, Asn48 and
      Leu60, which might be key to designing specific inhibitors for hOSF to fight
      osteoporosis and related bone-loss diseases. There are a total of 13 well defined
      water molecules forming hydrogen bonds with the above residues in and around the
      peptide-binding pocket. Some of those water molecules might be important for drug
      design approaches. The hOSF-SH3 structure at atomic resolution provides an
      accurate framework for structure-based design of its inhibitors.

PMID- 16946463
TI  - Structure of the stand-alone RAM-domain protein from Thermus thermophilus HB8.
AB  - The stand-alone RAM (regulation of amino-acid metabolism) domain protein SraA
      from Thermus thermophilus HB8 (TTHA0845) was crystallized in the presence of zinc
      ions. The X-ray crystal structure was determined using a multiple-wavelength
      anomalous dispersion technique and was refined at 2.4 A resolution to a final R
      factor of 25.0%. The monomeric structure is a betaalphabetabetaalphabeta fold and
      it dimerizes mainly through interactions between the antiparallel beta-sheets.
      Furthermore, five SraA dimers form a ring with external and internal diameters of
      70 and 20 A, respectively. This decameric structure is unique compared with the
      octameric and dodecameric structures found for other stand-alone RAM-domain
      proteins and the C-terminal RAM domains of Lrp/AsnC-family proteins.

PMID- 16946464
TI  - Expression, purification, crystallization and preliminary crystallographic
      analysis of BipD, a component of the Burkholderia pseudomallei type III secretion
      system.
AB  - A construct consisting of residues 10-310 of BipD, a component of the
      Burkholderia pseudomallei type III secretion system (T3SS), has been
      overexpressed as a GST fusion, cleaved from the GST tag and purified. Crystals
      were grown of native and selenomethionine-labelled BipD. The crystals grow in two
      different polymorphs from the same condition. The first polymorph belongs to
      space group C222, with unit-cell parameters a = 103.98, b = 122.79, c = 49.17 A,
      a calculated Matthews coefficient of 2.4 A(3) Da(-1) (47% solvent content) and
      one molecule per asymmetric unit. The second polymorph belongs to space group
      P2(1)2(1)2, with unit-cell parameters a = 136.47, b = 89.84, c = 50.15 A, and a
      calculated Matthews coefficient of 2.3 A(3) Da(-1) (45% solvent content) for two
      molecules per asymmetric unit (analysis of the self-rotation function indicates
      the presence of a weak twofold non-crystallographic symmetry axis in this
      P2(1)2(1)2 form). The native crystals of both forms give diffraction data to 2.7
      A resolution, while the SeMet-labelled P2(1)2(1)2 crystals diffract to 3.3 A
      resolution. A K(2)PtCl(4) derivative of the P2(1)2(1)2 form was also obtained and
      data were collected to 2.7 A with radiation of wavelength lambda = 0.933 A. The
      Pt-derivative anomalous difference Patterson map revealed two self-peaks on the
      Harker sections.

PMID- 16946465
TI  - Expression, limited proteolysis and preliminary crystallographic analysis of
      IpaD, a component of the Shigella flexneri type III secretion system.
AB  - IpaD, the putative needle-tip protein of the Shigella flexneri type III secretion
      system, has been overexpressed and purified. Crystals were grown of the native
      protein in space group P2(1)2(1)2(1), with unit-cell parameters a = 55.9, b =
      100.7, c = 112.0 A, and data were collected to 2.9 A resolution. Analysis of the
      native Patterson map revealed a peak at 50% of the origin on the Harker section v
      = 0.5, suggesting twofold non-crystallographic symmetry parallel to the b
      crystallographic axis. As attempts to derivatize or grow selenomethionine
      labelled protein crystals failed, in-drop proteolysis was used to produce new
      crystal forms. A trace amount of subtilisin Carlsberg was added to IpaD before
      sparse-matrix screening, resulting in the production of several new crystal
      forms. This approach produced SeMet-labelled crystals and diffraction data were
      collected to 3.2 A resolution. The SeMet crystals belong to space group C2, with
      unit-cell parameters a = 139.4, b = 45.0, c = 99.5 A, beta = 107.9 degrees . An
      anomalous difference Patterson map revealed peaks on the Harker section v = 0,
      while the self-rotation function indicates the presence of a twofold
      noncrystallographic symmetry axis, which is consistent with two molecules per
      asymmetric unit.

PMID- 16946466
TI  - Purification, identification and preliminary crystallographic studies of an
      allergenic protein from Lathyrus sativus.
AB  - A 24 kDa protein was purified from the seeds of Lathyrus sativus by ammonium
      sulfate fractionation and ion-exchange chromatography. The N-terminal amino-acid
      sequence showed significant homology with the 2S albumin class of seed storage
      proteins. The protein showed 85% sequence homology with the seed albumin of Pisum
      sativum within the 40 N-terminal residues. Crystals were obtained by the hanging
      drop vapour-diffusion method. The crystals belonged to space group P2(1)2(1)2(1),
      with unit-cell parameters a = 43.5, b = 82.7, c = 153.4 A.

PMID- 16946467
TI  - Crystallization and preliminary X-ray crystallographic studies of Mycobacterium
      tuberculosis CRP/FNR family transcription regulator.
AB  - CRP/FNR family members are transcription factors that regulate the transcription
      of many genes in Escherichia coli and other organisms. Mycobacterium tuberculosis
      H37Rv contains a probable CRP/FNR homologue encoded by the open reading frame
      Rv3676. The deletion of this gene is known to cause growth defects in cell
      culture, in bone marrow-derived macrophages and in a mouse model of tuberculosis.
      The mycobacterial gene Rv3676 shares approximately 32% sequence identity with
      prototype E. coli CRP. The structure of the protein might provide insight into
      transcriptional regulation in the pathogen by this protein. The M. tuberculosis
      CRP/FNR transcription regulator was crystallized in space group P2(1)2(1)2(1),
      with unit-cell parameters a = 54.1, b = 84.6, c = 101.2 A. The crystal diffracted
      to a resolution of 2.9 A. Matthews coefficient and self-rotation function
      calculations reveal the presence of two monomers in the asymmetric unit.

PMID- 16946468
TI  - Preliminary crystallographic characterization of an RNA helicase from Kunjin
      virus.
AB  - Kunjin virus is a member of the Flavivirus genus and is an Australian variant of
      West Nile virus. The C-terminal domain of the Kunjin virus NS3 protein displays
      helicase activity. The protein is thought to separate daughter and template RNA
      strands, assisting the initiation of replication by unwinding RNA secondary
      structure in the 3' nontranslated region. Expression, purification and
      preliminary crystallographic characterization of the NS3 helicase domain are
      reported. It is shown that Kunjin virus helicase may adopt a dimeric assembly in
      absence of nucleic acids, oligomerization being a means to provide the helicases
      with multiple nucleic acid-binding capability, facilitating translocation along
      the RNA strands. Kunjin virus NS3 helicase domain is an attractive model for
      studying the molecular mechanisms of flavivirus replication, while simultaneously
      providing a new basis for the rational development of anti-flaviviral compounds.

PMID- 16946469
TI  - Crystallization and preliminary crystallographic characterization of GumK, a
      membrane-associated glucuronosyltransferase from Xanthomonas campestris required
      for xanthan polysaccharide synthesis.
AB  - GumK is a membrane-associated inverting glucuronosyltransferase that is part of
      the biosynthetic route of xanthan, an industrially important exopolysaccharide
      produced by Xanthomonas campestris. The enzyme catalyzes the fourth glycosylation
      step in the pentasaccharide-P-P-polyisoprenyl assembly, an oligosaccharide
      diphosphate lipid intermediate in xanthan biosynthesis. GumK has marginal
      homology to other glycosyltransferases (GTs). It belongs to the CAZy family GT
      70, for which no structure is currently available, and indirect biochemical
      evidence suggests that it also belongs to the GT-B structural superfamily.
      Crystals of recombinant GumK from X. campestris have been grown that diffract to
      1.9 A resolution. Knowledge of the crystal structure of GumK will help in
      understanding xanthan biosynthesis and its regulation and will also allow a
      subsequent rational approach to enzyme design and engineering. The
      multiwavelength anomalous diffraction approach will be used to solve the phase
      problem.

PMID- 16946470
TI  - Crystallization and preliminary X-ray diffraction analysis of protein 14 from
      Sulfolobus islandicus filamentous virus (SIFV).
AB  - A large-scale programme has been embarked upon aiming towards the structural
      determination of conserved proteins from viruses infecting hyperthermophilic
      archaea. Here, the crystallization of protein 14 from the archaeal virus SIFV is
      reported. This protein, which contains 111 residues (MW 13 465 Da), was cloned
      and expressed in Escherichia coli with an N-terminal His(6) tag and purified to
      homogeneity. The tag was subsequently cleaved and the protein was crystallized
      using PEG 1000 or PEG 4000 as a precipitant. Large crystals were obtained of the
      native and the selenomethionine-labelled protein using sitting drops of 100-300
      nl. Crystals belong to space group P6(2)22 or P6(4)22, with unit-cell parameters
      a = b = 68.1, c = 132.4 A. Diffraction data were collected to a maximum
      acceptable resolution of 2.95 and 3.20 A for the SeMet-labelled and native
      protein, respectively.

PMID- 16946471
TI  - The purification, crystallization and preliminary structural characterization of
      PhzM, a phenazine-modifying methyltransferase from Pseudomonas aeruginosa.
AB  - Pyocyanin, phenazine-1-carboxylic acid and more than 70 related compounds
      collectively known as phenazines are produced by various species of Pseudomonas,
      including the fluorescent pseudomonad P. aeruginosa, a Gram-negative
      opportunistic pathogen in humans and animals. P. aeruginosa synthesizes a
      characteristic blue water-soluble compound called pyocyanin (1-hydroxy-5-methyl
      phenazine). Two enzymes designated PhzM and PhzS are involved in the terminal
      steps of its synthesis and very little is known about these enzymes. In this
      study, PhzM, a dimeric S-adenosylmethionine-dependent methyltransferase, was
      purified and crystallized from PEG 3350/sodium cacodylate/sodium citrate pH 6.5.
      The crystals belong to space group P1, with unit-cell parameters a = 46.1, b =
      61.8, c = 69.6 A, alpha = 96.3, beta = 106.6, gamma = 106.9 degrees . They
      contain one dimer in the asymmetric unit and diffract to a resolution of 1.8 A.
      Anomalous data to 2.3 A resolution have been collected from seleno-L-methionine
      labelled PhzM.

PMID- 16946472
TI  - Crystallization and preliminary crystallographic analysis of two Streptococcus
      agalactiae proteins: the family II inorganic pyrophosphatase and the
      serine/threonine phosphatase.
AB  - Streptococcus agalactiae, which infects human neonates and causes sepsis and
      meningitis, has recently been shown to possess a eukaryotic-like serine/threonine
      protein phosphorylation signalling cascade. Through their target proteins, the S.
      agalactiae Ser/Thr kinase and Ser/Thr phosphatase together control the growth as
      well as the morphology and virulence of this organism. One of the targets is the
      S. agalactiae family II inorganic pyrophosphatase. The inorganic pyrophosphatase
      and the serine/threonine phosphatase have therefore been purified and
      crystallized and diffraction data have been collected from their crystals. The
      data were processed using XDS. The inorganic pyrosphosphatase crystals diffracted
      to 2.80 A and the Ser/Thr phosphatase crystals to 2.65 A. Initial structure
      solution experiments indicate that structure solution will be successful in both
      cases. Solving the structure of the proteins involved in this cascade is the
      first step towards understanding this phenomenon in atomic detail.

PMID- 16946473
TI  - Expression, crystallization and preliminary X-ray analysis of the periplasmic
      stress sensory protein RseB from Escherichia coli.
AB  - Sensing external stress in the bacterial periplasm and signal transduction to the
      cytoplasm are important functions of the CpxAR, Bae and sigma(E) signalling
      pathways. In Escherichia coli, the sigma(E) pathway can be activated through
      degradation of the antisigma factor RseA by DegS and YaeL. The periplasmic
      protein RseB plays an important role in this pathway by exerting a direct or
      indirect negative effect on YaeL cleavage efficiency. RseB from E. coli, missing
      the periplasmic signal sequence (RseB(DeltaN)), was cloned, expressed, purified
      and crystallized. Crystals were obtained in two different forms belonging to
      space group P42(1)2 (form I) and C222(1) (form II) and diffracted to 2.8 and 2.4
      A resolution, respectively. In crystal form I two copies of the protein were
      located in the asymmetric unit according to heavy-atom analysis, while crystal
      form II contained three copies.

PMID- 16946474
TI  - Crystallization and preliminary crystallographic analysis of a novel plant type
      III polyketide synthase that produces pentaketide chromone.
AB  - Pentaketide chromone synthase (PCS) from Aloe arborescens is a novel plant
      specific type III polyketide synthase that catalyzes the formation of 5,7
      dihydroxy-2-methylchromone from five molecules of malonyl-CoA. Recombinant PCS
      expressed in Escherichia coli was crystallized by the hanging-drop vapour
      diffusion method. The crystals belonged to space group P2(1), with unit-cell
      parameters a = 73.2, b = 88.4, c = 70.0 A, alpha = gamma = 90.0, beta = 95.6
      degrees . Diffraction data were collected to 1.6 A resolution using synchrotron
      radiation at BL24XU of SPring-8.

PMID- 16946475
TI  - Crystallization and preliminary X-ray diffraction study of an active-site mutant
      of pro-Tk-subtilisin from a hyperthermophilic archaeon.
AB  - Crystallization of and preliminary crystallographic studies on an active-site
      mutant of pro-Tk-subtilisin from the hyperthermophilic archaeon Thermococcus
      kodakaraensis were performed. The crystal was grown at 277 K by the sitting-drop
      vapour-diffusion method. Native X-ray diffraction data were collected to 2.3 A
      resolution using synchrotron radiation from station BL41XU at SPring-8. The
      crystal belongs to the orthorhombic space group I222, with unit-cell parameters a
      = 92.69, b = 121.78, c = 77.53 A. Assuming the presence of one molecule per
      asymmetric unit, the Matthews coefficient V(M) was calculated to be 2.6 A(3) Da(
      1) and the solvent content was 53.1%.

PMID- 16946476
TI  - Crystallization and preliminary crystallographic studies of the Pasteurella
      multocida toxin catalytic domain.
AB  - The C-terminal catalytic domain of Pasteurella multocida toxin, which is the
      virulence factor of the organism in P. multocida, has been expressed, purified
      and subsequently crystallized using the sitting-drop vapour-diffusion technique.
      Native diffraction data to 1.9 A resolution were obtained at the BL44XU beamline
      of SPring-8 from a flash-frozen crystal at 100 K. The crystals belong to space
      group C2, with unit-cell parameters a = 111.0, b = 150.4, c = 77.1 A, beta =
      105.5 degrees, and are likely to contain one C-PMT (726 residues) per asymmetric
      unit.

PMID- 16946477
TI  - Cloning, expression, purification, crystallization and initial crystallographic
      analysis of the preprotein translocation ATPase SecA from Thermus thermophilus.
AB  - The Thermus thermophilus gene encoding the preprotein translocation ATPase SecA
      was cloned and expressed and the purified protein was crystallized by the hanging
      drop vapour-diffusion technique in two different space groups P3(1(2))21 (a = b =
      168.6, c = 149.8 A) and P6(1(5))22 (a = b = 130.9, c = 564.6 A). The crystals,
      improved by macroseeding, diffracted to beyond 2.8 and 3.5 A resolution for the
      trigonal and hexagonal crystal forms, respectively. Structure determination using
      the multiple isomorphous replacement method is in progress.

PMID- 16946478
TI  - Cloning, expression, purification, crystallization and preliminary X-ray analysis
      of peptidyl-tRNA hydrolase from Mycobacterium tuberculosis.
AB  - Peptidyl-tRNA hydrolase catalyses the cleavage of the ester link between the
      peptide and the tRNA in peptidyl-tRNAs that, for various reasons, have dropped
      off the translating ribosomes. This enzyme from Mycobacterium tuberculosis has
      been crystallized in three related but distinct forms: P2(1)2(1)2(1), unit-cell
      parameters a = 36.30, b = 61.85, c = 73.97 A, P2(1), a = 35.83, b = 73.79, c =
      59.79 A, beta = 92.3 degrees , and P2(1)2(1)2(1), a = 35.84, b = 57.06, c = 72.59
      A. X-ray data have been collected from all three forms.

PMID- 16946479
TI  - Purification, crystallization and preliminary X-ray crystallographic analysis of
      chitinase from Bacillus cereus NCTU2.
AB  - Chitinases (EC 3.2.1.14) are found in a broad range of organisms, including
      bacteria, fungi and higher plants, and play different roles depending on their
      origin. A chitinase from Bacillus cereus NCTU2 (ChiNCTU2) capable of hydrolyzing
      chitin as a carbon and nitrogen nutrient has been identified as a member of the
      family 18 glycoside hydrolases. ChiNCTU2 of molecular weight 36 kDa has been
      crystallized using the hanging-drop vapour-diffusion method. According to the
      diffraction of chitinase crystals at 1.10 A resolution, the crystal belongs to
      space group P2(1), with unit-cell parameters a = 50.79, b = 48.79, c = 66.87 A,
      beta = 99.31 degrees . Preliminary analysis indicates there is one chitinase
      molecule in the asymmetric unit, with a solvent content of 43.4%.

PMID- 16946480
TI  - Crystallization of mutant forms of glutaredoxin Grx1p from yeast.
AB  - Glutaredoxin Grx1p from yeast was crystallized both as an independent protein and
      in a protein fusion with His-tagged yellow fluorescent protein (rxYFP). A
      glutathionylated C30S mutant of the 12 kDa Grx1p was crystallized in two
      different forms in PEG 4000 at low pH. These orthorhombic and monoclinic forms
      diffract to 2.0 A (synchrotron radiation) and 2.7 A (rotating-anode generator),
      respectively. In contrast, rxYFP-Grx1p formed crystals at high pH in MgSO(4)
      which diffract synchrotron radiation to 2.7 A.

PMID- 16946481
TI  - Crystallization and preliminary X-ray diffraction analysis of rat protein
      tyrosine phosphatase eta.
AB  - The rat protein tyrosine phosphatase eta (rPTPeta) is a cysteine-dependent
      phosphatase which hydrolyzes phosphoester bonds in proteins and other molecules.
      rPTPeta and its human homologue DEP-1 are involved in neoplastic transformations.
      Thus, expression of the protein is reduced in all oncogene-transformed thyroid
      cell lines and is absent in highly malignant thyroid cells. Moreover, consistent
      with the suggested tumour suppression role of PTPeta, inhibition of the
      tumorigenic process occurs after its exogenous reconstitution, suggesting that
      PTPeta might be important for gene therapy of cancers. In this study, the
      catalytic domain of rPTPeta was produced in Escherichia coli in soluble form and
      purified to homogeneity. Crystals were obtained by the hanging-drop vapour
      diffusion method. Diffraction data were collected to 1.87 A resolution. The
      crystal belongs to space group P2(1)2(1)2(1), with unit-cell parameters a =
      46.46, b = 63.07, c = 111.64 A, and contains one molecule per asymmetric unit.

PMID- 16946482
TI  - Purification, crystallization and X-ray diffraction analysis of human
      synaptotagmin 1 C2A-C2B.
AB  - Synaptotagmin acts as the Ca(2+) sensor for neuronal exocytosis. The cytosolic
      domain of human synaptotagmin 1 is composed of tandem C2 domains: C2A and C2B.
      These C2 domains modulate the interaction of synaptotagmin with the phospholipid
      bilayer of the presynaptic terminus and effector proteins such as the SNARE
      complex. Human synaptotagmin C2A-C2B has been expressed as a glutathione-S
      transferase fusion protein in Escherichia coli. The purification, crystallization
      and preliminary X-ray analysis of this protein are reported here. The crystals
      diffract to 2.7 A and belong to the orthorhombic space group P2(1)2(1)2(1), with
      unit-cell parameters a = 82.37, b = 86.31, c = 140.2 A. From self-rotation
      function analysis, there are two molecules in the asymmetric unit. The structure
      determination of the protein using this data is ongoing.

PMID- 16946483
TI  - Cloning, expression, purification, crystallization and preliminary structure
      determination of glucose-1-phosphate uridylyltransferase (UgpG) from Sphingomonas
      elodea ATCC 31461 bound to glucose-1-phosphate.
AB  - The cloning, expression, purification, crystallization and preliminary
      crystallographic analysis of glucose-1-phosphate uridylyltransferase (UgpG) from
      Sphingomonas elodea ATCC 31461 bound to glucose-1-phosphate are reported.
      Diffraction data sets were obtained from seven crystal forms in five different
      space groups, with highest resolutions ranging from 4.20 to 2.65 A. The phase
      problem was solved for a P2(1) crystal form using multiple isomorphous
      replacement with anomalous scattering from an osmium derivative and a SeMet
      derivative. The best native crystal in space group P2(1) has unit-cell parameters
      a = 105.5, b = 85.7, c = 151.8 A, beta = 105.2 degrees . Model building and
      refinement are currently under way.

PMID- 16946484
TI  - Crystallization and preliminary crystallographic analysis of the tetrameric form
      of phosphofructokinase-2 from Escherichia coli, a member of the ribokinase
      family.
AB  - Escherichia coli contains two phosphofructokinases, Pfk-1 and Pfk-2, which belong
      to unrelated protein families. In addition to catalytic function, the enzymes
      have converged in showing substrate inhibition by the nucleotide MgATP. However,
      although both Pfk-1 and Pfk-2 have been extensively characterized biochemically,
      only the structure of the former has been solved by X-ray diffraction. In order
      to fully understand how the same function has evolved on different structural
      folds, Pfk-2 has been crystallized by the hanging-drop vapour-diffusion method
      using PEG 6000 as precipitant. Single crystals were grown in the presence of
      MgATP and diffracted to 1.98 A. The crystals belong to the orthorhombic system,
      space group P222(1), with unit-cell parameters a = 42.8, b = 86.8, c = 171.3 A.
      The calculated Matthews coefficient of 2.45 A(3) Da(-1) indicates the presence of
      two monomers in the asymmetric unit, corresponding to a solvent content of 49%.
      Structure determination is ongoing.

PMID- 16946485
TI  - Crystallization and X-ray data analysis of the 10 kDa C-terminal lid subdomain
      from Caenorhabditis elegans Hsp70.
AB  - Hsp70 is an important molecular chaperone involved in the regulation of protein
      folding. Crystals of the C-terminal 10 kDa helical lid domain (residues 542-640)
      from a Caenorhabditis elegans Hsp70 homologue have been produced that diffract X
      rays to approximately 3.4 A. Crystals belong to space group I2(1)2(1)2(1), with
      unit-cell parameters a = b = 197, c = 200 A. The Matthews coefficient, self
      rotation function and Patterson map indicate 24 monomers in the asymmetric unit,
      showing non-crystallographic 432 symmetry. Molecular-replacement studies using
      the corresponding domain from rat, the only eukaryotic homologue with a known
      structure, failed and a mercury derivative was obtained. Preliminary MAD phasing
      using SHELXD and SHARP for location and refinement of the heavy-atom substructure
      and SOLOMON for density modification produced interpretable maps with a clear
      protein-solvent boundary. Further density-modification, model-building and
      refinement are currently under way.

PMID- 16946486
TI  - A novel strategy for a drug delivery system using a claudin modulator.
AB  - With the continued progress in genomic drug discovery, the high-throughput
      production of drug candidates has become possible, and thus today there are a
      number of candidates that are extremely effective both in cell-free and in cell
      models. However, a drug delivery system suitable for the high-throughput
      production has yet to be fully developed. In tissues, the tight junction (TJ)
      plays a pivotal role as both a barrier to restrict various substances and in
      intra-tissue maintenance. Claudin, a ca. 23 kDa transmembrane protein with four
      transmembrane domains, is responsible for the TJ functions. Interestingly, for
      each of the 24 members of the claudin family, expression profiles and exact
      barrier functions differ. Therefore, claudin may be a potential target for use as
      a drug delivery system via a paracellular route. The C-terminal fragment of
      Clostridium perfringens enterotoxin (C-CPE) is known to modulate the barrier
      function of claudin. We found that C-CPE is a potent absorption-enhancer and that
      this enhancing activity is 400-fold greater than clinically used enhancers. The
      enhancing activity examined in this study involved an interaction between C-CPE
      and claudin-4. These findings indicate that claudin might be a novel target for a
      drug delivery system. In the current review, we describe about background and
      data on our research about claudin modulator, and we also discuss the possibility
      of the use of the claudin family in a new approach for developing a drug delivery
      system.

PMID- 16946487
TI  - Nanocarriers: promising vehicle for bioactive drugs.
AB  - Development of new delivery systems that deliver the potential drug specifically
      to the target site in order to meet the therapeutic needs of the patients at the
      required time and level remains the key challenge in the field of pharmaceutical
      biotechnology. Developments in this context to achieve desired goal has led to
      the evolution of the multidisciplinary field nanobiotechnology which involves the
      combination of two most promising technologies of 21st century--biotechnology and
      nanotechnology. Nanobiotechnology encompasses a wide array of different
      techniques to improve the delivery of biotech drugs, and nanoparticles offer the
      most suitable form whose properties can be tailored by chemical methods. This
      review highlights the different types of nanoparticulate delivery systems
      employed for biotech drugs in the field of molecular medicine with a short
      overlook at its applications and the probable associated drawbacks.

PMID- 16946488
TI  - Differential induction of cystathionine gamma-lyase in the livers and kidneys of
      mouse dams during gestation and lactation.
AB  - Cystathionine gamma-lyase (CSE) is the last key enzyme in the transsulfuration
      pathway for the biosynthesis of cysteine from methionine in mammals, and
      catalyzes the hydrolysis of cystathionine into cysteine. Cysteine can be provided
      through diet; however, several investigators have suggested that infants may
      require dietary supplements of cysteine because of very low or undetectable CSE
      activity in their livers. We have previously shown that CSE levels are much lower
      in the livers and kidneys of fetal and infant mice than in those of adult mice,
      suggesting that the maternal supply of cysteine is important for the early
      development of mice. Here we examined changes of CSE expression in the livers and
      kidneys of dams during gestation and lactation. Hepatic enlargement was observed
      as early as gestational day 12.5 (G12.5) and thereafter became more prominent,
      whereas expression of CSE in the livers was found after postpartum day 1 (P1) and
      reached a peak at P14. The maintenance of lactation was essential for both
      hepatic enlargement and CSE expression. In contrast, kidneys gained weight only
      slightly during lactation while CSE expression in kidneys was markedly induced at
      G15.5 and then gradually declined through to P28. Serum concentrations of
      homocysteine (the precursor of cystathionine) were significantly lower in G18.5
      dams than in virgins or G15.5 dams, suggesting that the expression of CSE in the
      kidneys contributes to the effective clearance of homocysteine during the late
      gestational stage.

PMID- 16946489
TI  - Antitumoral activity of 13-demethyl or 13-substituted analogues of all-trans
      retinoic acid and 9-cis retinoic acid in the human myeloid leukemia cell line HL
      60.
AB  - The antitumoral activity of 13-demethyl or 13-substituted all-trans retinoic acid
      (ATRA) and 9-cis retinoic acid (9CRA) was tested using the myeloid leukemia cell
      line HL-60. Cell proliferation, differentiation and apoptosis were evaluated by
      flow cytometry and DNA fragmentation assay. The ability to bind to human RXRalpha
      and to activate either human retinoic acid response element (RARE)-mediated gene
      expression or rat CRABPII retinoid X response element (RXRalpha)-mediated gene
      expression were determined using luciferase reporter plasmids. In terms of the
      magnitude of the regulatory activity for the proliferation and differentiation of
      HL-60 cells, the compounds ranked as follows: ATRA>13-ethyl ATRA>13-demethyl
      ATRA>13-phenylethyl ATRA>13-propyl ATRA>13-butyl ATRA (ATRA analogues) and
      9CRA>13-ethyl 9CRA>13-demethyl 9CRA>13-propyl 9CRA>13-phenetyl 9CRA>13-butyl 9CRA
      (9CRA analogues). Regarding the magnitude of the apoptosis-inducing activity, the
      order was: 9CRA>13-ethyl 9CRA>13-demethyl 9CRA, with ATRA and its analogues and
      the other 9CRA analogues virtually inactive. Similar trends were observed in
      binding affinity for RXRalpha and transactivation activity toward RARE- or RXRE
      mediated gene expression. The results clearly indicate that the presence of a
      methyl group at C-13 is essential for the antitumoral activity of ATRA and 9CRA,
      and that bulky substituents exceeding two carbon atoms or the absence of
      substitution at position 13 significantly reduce the binding affinity for RAR and
      RXR, leading to a decreased RAR/RARE and/or RXR/RXRE-mediated gene expression.

PMID- 16946490
TI  - Biochemical characterization of suramin as a selective inhibitor for the PKA
      mediated phosphorylation of HBV core protein in vitro.
AB  - The inhibitory effect of suramin on the phosphorylation of GST-HBV core fusion
      protein (GST-Hcore) and two GST-Hcore fusion polypeptides (Hcore157B and
      Hcore164B) by two alpha-type cAMP-dependent protein kinases (PKAIalpha and
      PKAIIalpha) was biochemically investigated in vitro. It was found that (i) this
      phosphorylation was inhibited by suramin at a low concentration (IC(50)=approx.
      10 nM); (ii) a relative high dose of suramin was required to inhibit an
      autophosphorylation of PKAIIalpha (IC(50)=approx. 0.7 muM) and the PKAIIalpha
      mediated phosphorylation of histone H2B (IC(50)=approx. 0.4 muM); (iii) the
      PKAIIalpha-mediated phosphorylation of Hcore157B was more sensitive to suramin
      than the phosphorylation of Hcore157B by Ca(2+)-dependent protein kinase (PKC);
      and (iv) suramin had a high binding affinity for Hcore157B, but not for histone
      H2B in vitro. These results suggest that suramin selectively inhibits the PKA
      mediated phosphorylation of HBV-CP through the direct binding in vitro of suramin
      to the Arg-rich C-terminal region (containing three potential phosphorylation
      sites for PKA) on HBV-CP.

PMID- 16946491
TI  - The small heat shock protein alphaB-crystallin inhibits differentiation-induced
      caspase 3 activation and myogenic differentiation.
AB  - Myoblasts respond to growth factor deprivation either by diffentiation into
      multinucleated myotubes or by undergoing apoptosis. The induction of apoptosis
      and differentiation in myogenic lineage may use overlapping cellular mechanisms.
      Here we demonstrate that the expression of the small heat shock protein alphaB
      crystallin as well as MyoD and myogenin is induced during myogenic
      differentiation in C2C12 cells, and these inductions occur at an early stage in
      the differentiation in vitro. To investigate the effect of alphaB-crystallin on
      myogenic differentiation and apoptosis, C2C12 cells were infected with adenovirus
      vector bearing full-length alphaB-crystallin cDNA. Overexpression of alphaB
      crystallin in C2C12 cells suppressed differentiation-induced apoptosis and
      activation of caspase 3, and also decreased the expression of MyoD and myogenin
      during myogenic differentiation of C2C12 cells induced by the differentiation
      medium. Our findings suggest that stress such as growth factor deprivation plays
      an important role in triggering apoptosis associated with myogenic
      differentiation and alphaB-crystallin suppressed the differentiation, apoptosis
      and caspase 3 activity.

PMID- 16946492
TI  - Caffeic acid protects hydrogen peroxide induced cell damage in WI-38 human lung
      fibroblast cells.
AB  - Cytoprotective effect of caffeic acid (3,4-dihydroxy cinnamic acid) on human lung
      fibroblast (WI-38) cells against hydrogen peroxide induced damage was
      investigated. Caffeic acid was found to scavenge intracellular reactive oxygen
      species, and 1,1-diphenyl-2-picrylhydrazyl radical, and thus prevented lipid
      peroxidation. The caffeic acid protected cell damage of WI-38 cells exposed to
      hydrogen peroxide (H(2)O(2)), via the activation of extracellular signal
      regulated kinase protein. Caffeic acid increased the activity of catalase and its
      protein expression. Hence, from the present study, it is suggestive that caffeic
      acid protects WI-38 cells against H2O2 damage by enhancing the cellular
      antioxidant activity.

PMID- 16946493
TI  - Segmental heterogeneity of epithelial ion transport induced by stimulants in rat
      distal colon.
AB  - Mammalian colon plays an important role in electrolyte and water balance, and
      exhibits significant segmental heterogeneity. The different responses to
      stimulants even exist in different segments of rat distal colon. The present
      study focus on the segmental heterogeneity of epithelial responses to different
      stimulants and investigates the possible mechanism by using short circuit current
      recording technique. Baseline I(SC) in the segment 4 of distal colon (DC(4),
      20.8+/-2.8 microA.cm(-2)) was significantly lower than that in the segment 1 of
      distal colon (DC(1), 40.5+/-1.9 microA.cm(-2)). Basolateral application of
      indomethacin induced a larger reduction of the baseline I(SC) in DC(4) (-28.2+/
      3.9 microA.cm(-2)) than that in DC(1) (-10.1+/-3.9 microA.cm(-2)). Moreover DC(4)
      are more sensitive to foskolin (a cAMP activator, apical side), Ach (basolateral
      side) and 5-HT (basolateral side) than DC(1), which was not affected by
      pretreatment with amiloride, a blocker of epithelial Na(+) channel. Basolateral
      pretreatment with atropine (muscarinic cholinergic receptor antagonist) for 10
      min, Ach-induced DeltaI(SC) increases in both DC(1) and DC(4 )were totally
      blocked. Otherwise, 5-HT(4) receptor antagonist GR113808 (basolateral side) and
      SB-204070 (basolateral side) completely inhibited 5-HT-induced I(SC) increases in
      both DC(1) and DC(4). Taken together, the results suggested that the segmental
      heterogeneity of epithelial responses to different stimulants exists in rat
      distal colon. And it is more likely related to the dissimilar distribution of
      membrane proteins involved in the ion transports within different segments of rat
      distal colon.

PMID- 16946494
TI  - A homeodomain-zinc finger protein, ZFHX4, is expressed in neuronal
      differentiation manner and suppressed in muscle differentiation manner.
AB  - Human ZFHX4 has recently been shown to be a candidate gene for congenital
      bilateral isolated ptosis. Here, we report molecular cloning of the human ZFHX4
      cDNA and genomic organization of this gene. Human ZFHX4 is about 180 kb long,
      containing 12 exons that encodes a 3599-amino acid protein carrying four
      homeodomains and 22 zinc fingers. The 11th exon is 3.2 kb in length and encodes
      all the four homeodomains together with four of the 22 zinc fingers. ZFHX4 is 90%
      homologous to mouse Zfhx4, 52% to human ATBF1A and 24% to Drosophila ZFH-2. ZFHX4
      was mapped to human chromosome 8q13.3-q21.11 by fluorescence in situ
      hybridization using BAC clone RP11-48D4 as a probe. RT-PCR analysis showed that
      ZFHX4 transcripts were expressed in adult human brain, liver and muscle. This,
      together with the finding that Zfhx4 was expressed transiently in differentiating
      P19 embryonal carcinoma cells and C2C12 myoblasts, suggests that ZFHX4/Zfhx4 is
      involved in neural and muscle differentiation.

PMID- 16946495
TI  - ATP-binding and -hydrolysis activities of ALDP (ABCD1) and ALDRP (ABCD2), human
      peroxisomal ABC proteins, overexpressed in Sf21 cells.
AB  - The peroxisomal ATP-binding cassette (ABC) proteins, adrenoleukodystrophy protein
      (ALDP, ABCD1) and ALD-related protein (ALDRP, ABCD2), were expressed in
      Spodoptera frugiperda 21 (Sf21) insect cells using a baculovirus-mediated
      expression system. Immunoelectron microscopy and subcellular fractionation
      revealed that the overexpressed ALDP was distributed in various subcellular
      organelles including mitochondria, nucleus and peroxisomes. The ALDP was not
      extractable with Na(2)CO(3) treatment, suggesting that it integrated into
      membranes. ATPase activity was detected in the membrane fraction expressing ALDP.
      The nucleotide-binding capacities of the expressed ALDP were estimated by the
      binding to ATP- or ADP-agarose. ALDP exhibited an affinity to both ADP and ATP.
      In contrast, ALDRP exhibited an affinity to ADP but scarcely to ATP. The ALDP in
      the Sf21 membrane fraction was extracted with n-dodecyl-beta-maltoside and
      successively purified with a chelate column. The nucleotide-binding and ATPase
      activities of the purified ALDP were, however, not detected. It may be that
      certain membranous components are required for the activity. We demonstrate for
      the first time that the peroxisomal ABC proteins can be expressed in Sf21
      membranes maintaining their nucleotide-binding abilities and ATPase activities,
      and the expressed proteins will be of use for further characterization.

PMID- 16946496
TI  - Antiviral targets of a chromene derivative from Sargassum micracanthum in the
      replication of human cytomegalovirus.
AB  - A chromene derivative (1) obtained from a brown alga, Sargassum micracanthum, has
      been proved to be a potent inhibitor of human cytomegalovirus (HCMV). In the
      present study, we evaluated its mode of action by various experimental assays.
      Time-of-addition experiments revealed that 1 was active if applied to cells
      before viral DNA synthesis, indicating that it inhibited early events of virus
      replication including virus adsorption and penetration, and a step immediately
      after viral internalization. Virus attachment and penetration studies suggested
      that one of the targets for anti-HCMV action of 1 was virus adsorption to cells
      and to a lesser extent, virus internalization was delayed in the presence of the
      compound. Pretreatment of virus particles with 1 showed that the compound exerted
      dose-dependent virucidal action. The chromene derivative and ganciclovir (GCV),
      an anti-HCMV drug, were synergistic inhibitors when used in combination. The
      synergistic effect could be explained by inhibition of different steps in HCMV
      replication cycle produced by 1 and GCV.

PMID- 16946497
TI  - Recombinant single-chain anti-idiotypic antibody: an effective fungal beta-1,3
      glucan synthase inhibitor.
AB  - Recombinant single-chain fragment variable anti-idiotypic antibodies were
      produced to represent the internal image of HM-1 killer toxin and were used as
      novel and effective antifungal agents to inhibit in vitro beta-1,3-glucan
      synthase and cell growth. The mechanism of cytocidal activity of anti-idiotypic
      antibodies was investigated and was compared with the actions of aculeacin A and
      papulacandin B, the most common antibiotics acting as beta-1,3-glucan synthase
      inhibitors. The degree of inhibition of beta-1,3-glucan synthase by both
      antibodies and antibiotics were examined for yeasts Saccharomyces cerevisiae
      A451, Cryptococcus albidus NBRC 0612 and Candida albicans IFM 40215. Although the
      mechanism of actions of the anti-idiotypic antibodies and antibiotics seems
      identical, the IC(50) values for the various yeasts used in this study confirmed
      that anti-idiotypic antibodies could be used as more effective fungal beta-1,3
      glucan synthase inhibitors than those of antibiotics.

PMID- 16946498
TI  - Beta-mannosyl linkages negatively regulate anaphylaxis and vasculitis in mice,
      induced by CAWS, fungal PAMPS composed of mannoprotein-beta-glucan complex
      secreted by Candida albicans.
AB  - Candida albicans water soluble fraction (CAWS) is a water-soluble extracellular
      mannoprotein-beta-glucan complex obtained from the culture supernatant of Candida
      albicans, which grows in a chemically defined medium. CAWS induced toxic
      reactions, such as acute anaphylactoid reaction, by intravenous administration
      and coronary arteritis by intraperitoneal administration. To clarify the
      structure responsible for these toxic reactions, C. albicans was cultured in pH-
      and temperature-controlled conditions and prepared with CAWS with or without the
      beta-1,2-linked mannosyl segment (BM). The structure of CAWS was assessed by
      immunochemical and spectroscopic methodologies, and we found that CAWS prepared
      under the natural culture conditions contained only small amounts of BM and CAWS
      prepared at neutral conditions at 27 degrees C contained a significantly higher
      percentage of BM. Both the acute lethal toxicity and coronary arteritis induction
      was significantly more severe in the absence of BM. Activation of a complement
      pathway, the lectin pathway, by CAWS was significantly stronger in the absence of
      BM. These facts strongly suggest that BM linkages in CAWS negatively modulate
      acute and chronic toxicity of CAWS, and may be strongly related to the lectin
      pathway of the complement activation.

PMID- 16946499
TI  - Inhibitory effects of Korean red ginseng and its genuine constituents
      ginsenosides Rg3, Rf, and Rh2 in mouse passive cutaneous anaphylaxis reaction and
      contact dermatitis models.
AB  - The inhibitory effects of the Korean red ginseng (steamed root of Panax ginseng
      C.A. MEYER, family Araliaceae) saponin fraction (KRGS) and its constituents
      ginsenosides Rg3, Rf, and Rh2 in mouse passive cutaneous anaphylaxis (PCA) and
      contact dermatitis models were measured. Orally administered KRGS and its genuine
      ginsenosides potently inhibited the PCA reaction induced by IgE. However, when
      these ginsenosides were intraperitoneally administered, ginsenoside Rh2 showed
      the most potent inhibition. The ginsenoside Rh2 also the most potently inhibited
      the beta-hexosaminidase release from RBL-2H3 cells induced by IgE with antigen.
      KRGS administered topically at a dose of 0.1% suppressed ear swelling in an
      oxazolone-induced mouse contact dermatitis model by 38.8%. Its constituents
      ginsenosides Rg3, Rf, and Rh2 at a concentration of 0.05% also potently
      suppressed mouse ear swelling by 47.5%, 34.8%, and 49.9% at 16 d, respectively.
      These ginsenosides also significantly reduced mRNA expression levels of
      cyclooxygenase (COX)-2, interleukin (IL)-1beta, tumor necrosis factor-alpha and
      interferon-gamma induced by oxazolone applied to mouse ears. However, the
      ginsenosides, except for ginsenoside Rh2, almost did not notably reduce IL-4
      levels. The ginsenoside Rh2 also potently inhibited COX-2 and inducible NO
      synthetase protein expression in liphopolysaccharide-stimulated RAW264.7 cells.
      Based on these findings, KRGS and its ginsenosides are suggested to improve
      atopic and contact dermatitis by regulating expression of cytokines.

PMID- 16946500
TI  - Neuroprotection of nicotiflorin in permanent focal cerebral ischemia and in
      neuronal cultures.
AB  - Nicotiflorin is a single component extracted from traditional Chinese medicine
      Flos Carthami. In this study, we investigated its neuroprotection in permanent
      focal cerebral ischemia model in rats, and in an in vitro model of ischemia. At
      doses of 2.5, 5 and 10 mg/kg, nicotiflorin administered immediately after the
      onset of ischemia markedly reduced brain infarct volume and neurological
      deficits. For primarily cultured neurons suffered 2 h hypoxia followed by 24 h
      reoxygenation, nicotiflorin significantly attenuated cell death and reduced LDH
      release. Morphological observation also directly confirmed its protective effect
      on neuron. These results provided strong pharmacological basis for its potential
      therapeutic role in cerebral ischemic illness.

PMID- 16946501
TI  - Fas/FasL signaling allows extracelluar-signal regulated kinase to regulate
      cytochrome c release in oridonin-induced apoptotic U937 cells.
AB  - Previously, we found that human histocytic lymphoma U937 cells possessed high
      susceptibility to oridonin-induced cell death, but the molecular mechanisms in
      response to oridonin remain unclear. In this study, U937 cells showed susceptible
      to apoptosis induced by 27 microM oridonin and an agonistic anti-Fas IgM mAb (CH
      11) (500 ng/ml) as a Fas-sensitized positive control. Caspase 8 inhibitor z-IETD,
      but neither caspase 1 inhibitor Ac-YVAD nor caspase 10 inhibitor z-AEVD,
      effectively blocked oridonin-induced cell death as well as DNA fragmentation.
      Western blot analysis showed the up-regulated expression of Fas, FasL, and FADD,
      and down-regulated expression of procaspase 8, suggesting that Fas/FasL pathway
      was activated in oridonin-induced cell apoptosis. Further, stimulation of U937
      cells with oridonin and CH11 resulted in significant ERK MAPK activation.
      However, inhibition of ERK by PD98059 reversed oridonin-induced cell death as
      well as the activation of caspase 8, indicating that ERK-mediated control occured
      upstream of caspase 8. Simultaneously, ERK activation accounted for the release
      of cytochrome c, but failed to influence decreased Bcl-2 expression induced by
      oridonin. Taken together, these results suggest that Fas/FasL signaling pathway
      mediated ERK activation sensitized U937 cells to mitochondrial pathway-mediated
      apoptosis induced by oridonin.

PMID- 16946502
TI  - Protective effects of breviscapine on ischemic vascular dementia in rats.
AB  - Breviscapine, a traditional Chinese medicine, is extensively used in clinic to
      treat cardiovascular diseases and cerebrovascular injury. In this study, we
      demonstrated the effects of breviscapine on vascular dementia (VD) rats, which
      were mimicked by permanent occlusion of bilateral common carotid arteries.
      Breviscapine (2 mg/kg for 14 d) improved the performance of learning and memory
      of VD rats in Morris water maze, decreased the level of lipid peroxidation and
      free radicals, and attenuated the pathological alterations, such as nuclear
      shrink, cellular edema and irregular arrangement of pyramidal layer in the
      hippocampal CA(1) area. In vitro experiment, breviscapine (50 microg/l) protected
      cortical neuron from injury and decreased intracellular calcium overloading
      induced by H2O2 (10 mM). The results suggest that breviscapine has therapeutic
      effect on cerebral ischemia and vascular dementia.

PMID- 16946503
TI  - Effective blood concentration of micafungin for pulmonary aspergillosis.
AB  - We previously reported that a 150 mg or higher daily dose is necessary for
      treatment of pulmonary aspergillosis with micafungin (MCFG) alone in patients
      with blood diseases. Since a delay in the treatment of pulmonary aspergillosis
      has a major influence on patient survival, clarification of the effective blood
      concentration of MCFG enables rapid treatment. Establishment of an appropriate
      dose is also useful for reducing the risk of adverse effects, such as MCFG
      induced impairment of liver function. Aiming for the rapid and safe treatment of
      pulmonary aspergillosis, we established new clinical diagnostic criteria of
      mycosis and MCFG therapeutic effect judgment criteria, and investigated the
      effective blood concentration of MCFG for mycosis. The blood trough level of MCFG
      in patients with blood diseases at each clinical improvement rating of pulmonary
      aspergillosis was 5.23+/-2.44 microg/ml in markedly improved cases, 4.08+/-2.63
      microg/ml in improved cases, and 3.45+/-1.63 microg/ml in successfully prevented
      cases, showing no significant difference among the 3 groups. Based on this
      finding, it is advisable to target a 5 microg/ml or higher blood trough level of
      MCFG in establishing the dose for aspergillosis in patients with blood diseases.

PMID- 16946504
TI  - Characterization of anti-neurodegenerative effects of Polygala tenuifolia in
      Abeta(25-35)-treated cortical neurons.
AB  - Although Polygala tenuifolia WILLD (PT) was classically mentioned as an anti
      dementia drug in Chinese and Japanese traditional medicine, basic research showed
      only enhancement of the cholinergic function. In Alzheimer's disease, neuritic
      atrophy and synaptic loss occur prior to neuronal death event, and may be the
      first trigger of the memory impairment. Therefore, we studied effects of Polygala
      tenuifolia WILLD (PT) on Abeta(25-35)-induced neuronal damage using rat cortical
      neurons for characterization of activities of PT under Abeta-induced neuronal
      damage. Treatment with the water extract of PT enhanced axonal length dose
      dependently after Abeta(25-35)-induced axonal atrophy. However, dendritic atrophy
      and synaptic loss induced by Abeta(25-35) were not recovered by treatment with PT
      extract. In contrast, Abeta(25-35)-induced cell damage was completely inhibited
      by PT extract. By characterization of PT effects on neuronal morphological
      plasticity and cell damage, usefulness as well as an insufficiency of PT as an
      anti-dementia drug was clarified.

PMID- 16946505
TI  - Augmentation of endothelin-1-induced phosphorylation of CPI-17 and myosin light
      chain in bronchial smooth muscle from airway hyperresponsive rats.
AB  - Airway hyperresponsiveness (AHR) associated with heightened airway resistance and
      inflammation is a characteristic feature of bronchial asthma. It has been
      demonstrated that contraclile responsiveness to endothelin-1 (ET-1) in repeated
      antigen challenge-induced airway hyperresponsive bronchial preparation was
      significantly increased. ET-1 is a potent contracting substance for various
      smooth muscles including airways. In addition to the classical Ca(2+)-mediated
      contraction, ET-1 also induced Ca(2+) sensitization of contraction. However, it
      is not clear whether ET-1 stimulation also activates the CPI-17 (PKC-potentiated
      inhibitory protein for heterotrimeric myosin light chain phosphatase of 17 kDa)
      pathway in airway smooth muscles. Therefore, the changes in ET-1-induced
      activation/phosphorylation of CPI-17 and myosin light chain (MLC) in bronchial
      smooth muscle of repeatedly antigen-challenged rats were examined. The levels of
      ET-1-induced phosphorylation of CPI-17 and MLC were increased much more markedly
      in the AHR group than in the sensitized control animals. It might be suggested
      that the augmented activation of CPI-17 observed in the hyperresponsive bronchial
      smooth muscle is responsible for the enhanced agonists-induced contraction of
      bronchial smooth muscle in AHR rats.

PMID- 16946506
TI  - Silibinin protects rat cardiac myocyte from isoproterenol-induced DNA damage
      independent on regulation of cell cycle.
AB  - Silibinin, derived from the milk thistle plant, Silybum marianum, has been
      traditionally used as an antihepatotoxic agent for the treatment of liver
      disease. Our preliminary study demonstrated that silibinin has protected rat
      cardiac myocytes against beta-adrenergic agonist isoproterenol-induced injury
      through resuming mitochondrial function and regulating the expression of SIRT1
      and Bcl-2 family members. In this study, we investigate whether silibinin has
      anti-apoptotic effect on isoproterenol-treated rat cardiac myocytes. DNA damage,
      detected by the TUNEL and DNA fragmentation assay, was diminished after treatment
      of silibinin. Results of nitrite and Western blot assays showed that the amount
      of NO and the expression of iNOS were decreased after treatment with silibinin,
      while the expression of procaspase-3 and digestion of caspase-3 substrates, the
      inhibitor of caspase-activated DNase (ICAD) and poly-(ADP-ribose) polymerase
      (PARP), were increased simultaneously. The DNA damage was reversed by down
      regulation of p53 phosphorylation after treatment with silibinin. Result of
      flowcytometric analysis showed that the cell cycle was not affected, and the
      expression of cell cycle regulatory protein p21 also had no change. Consequently,
      silibinin protected cardiac myocytes against isoproterenol-induced DNA damage
      through caspase pathway and the expression of p53, but independent on regulation
      of cell cycle.

PMID- 16946507
TI  - In vitro antioxidant studies on the benzyl tetra isoquinoline alkaloid berberine.
AB  - Berberine is a benzyl tetra isoquinoline alkaloid which is widely used as an
      antimicrobial and an antidiarrhoeal. As berberine containing plants are virtually
      used in all forms of traditional medicine, our study aimed to examine the
      antioxidant activity of berberine using 2,2-diphenyl 1-picrylhydrazyl (DPPH)
      radical scavenging, nitric oxide scavenging, lipid peroxidation, superoxide
      scavenging, iron chelating activity and 2,2-azino bis(3-ethylbenzothiazoline-6
      sulfonate) (ABTS) radical scavenging methods. The IC(50) values for all the
      models were calculated by regression analysis. In all the models tested,
      berberine showed its ability to scavenge the free radicals in a concentration
      dependent manner. The present study thereby justifies the therapeutic potential
      of berberine.

PMID- 16946508
TI  - Identification and characterization of antioxidants from Sophora flavescens.
AB  - The objectives of this study were to investigate the radical-scavenging activity
      and protective potential of Sophora flavescens from oxidative damage by the
      radical generator 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH) in renal
      epithelial LLC-PK(1) cells and to identify the active components using the
      bioassay-linked fractionation method. The MeOH extract and fractions of
      CH(2)Cl(2), BuOH, and H(2)O from S. flavescens showed 1,1-diphenyl-2
      picrylhydrazyl (DPPH) radical-scavenging effects in a dose-dependent manner
      (p<0.01),whereas only the BuOH and CH(2)Cl(2) fractions showed protective effects
      against LLC-PK(1) cellular damage induced by AAPH in a dose-dependent manner
      (p<0.01). In particular, the BuOH fraction had the most effective (p<0.05)
      antioxidative capacity. Employing a bioassay-linked HPLC/MS method, the active
      constituents from the BuOH fraction of S. flavescens were isolated and
      characterized as sophoraflavanone G and kurarinone with potent antioxidant
      effects against the DPPH radical, with IC(50) values of 5.26 and 7.73 microg/ml,
      respectively. Moreover, the compounds dose dependently recovered cell viability
      decreased by AAPH treatment (p<0.01), suggesting their protective roles against
      cellular oxidative damage. The results of this study suggest that S. flavescens
      has excellent antioxidative and kidney-protective potential and that flavonoids
      from S. flavescens, i.e., sophoraflavanone G and kurarinone, are the active
      constituents.

PMID- 16946509
TI  - Reproductive effects of ethnomedicinal formulation of tape-vine leaves in female
      rats.
AB  - Documented ethno-contraceptive use of Tape-vine or Stephania japonica (THUNB.)
      MIERS., Syn. Stephania hernandifolia (WILLD.) WALP. leaves is evaluated with
      regards to post-coital pregnancy interceptive activity of its aqueous extract
      (AE) and an ethnomedicinal formulation (EF) in Wistar rats. EF at 500 and 250
      mg/kg doses induced 66.7% and 33.3% post-coital pregnancy interception
      respectively and the higher dose exhibited significant reduction in number of
      litters born and also anti-implantation property. In contrast, none of the dose
      levels of AE interfered in pregnancy but significant anti-implantation property
      was observed at doses of 2 and 1 g/kg, even as the higher dose produced
      significant reduction in number of litters born as well. EF at 500 mg/kg also
      exhibited significant uterotrophic activity and histological changes in uterus.
      Pair-wise comparison of sex hormone-levels exhibited significant increment in
      serum estradiol, LH and FSH but decrease in progesterone levels. Assessed blood
      lipid-carbohydrate profile exhibited substantial decrease in glucose,
      cholesterol, VLDL and triglyceride contents and significant increase in HDL. It
      is concluded that EF probably acts as better post-coital pregnancy interceptive
      agent through restriction of implantation by alteration of gonadal hormone levels
      and decline in blood-glucose levels that possibly disrupts oxidative energy
      metabolism in uterus during implantation. High surge in LH and FSH suggests
      negligible interference in ovulatory mechanism. This preparation also seems to be
      free of cardiovascular risk factors. HPTLC and HPLC analysis of both EF and AE
      exhibited marked chemical differences.

PMID- 16946510
TI  - Influence of mouth washing procedures on the removal of drug residues following
      inhalation of corticosteroids.
AB  - Mouth washing after inhalation of corticosteroids is effective for prevention of
      local adverse effects such as hoarseness and oropharyngeal candidiasis. To
      establish an optimal procedure for such mouth washing, we investigated the
      removal rates of drug residues remaining on the oropharyngeal mucosa using
      various mouth washing methods following inhalation. A beclomethasone dipropionate
      metered dose inhaler (BDP-MDI) (100 microg) and a fluticasone propionate dry
      powder inhaler (FP-DPI) (100 microg) were used. The effects of different mouth
      washing methods were evaluated by quantification of drugs in the expectorated
      rinse solution using an HPLC method. The amounts of BDP recovered in the rinse
      after gargling and rinsing for 5 s each were 47.1+/-13.6 microg, while they were
      42.9+/-9.4 microg after rinsing alone for 10 s and 38.7+/-9.2 microg after
      gargling alone for 10 s. Under the same conditions, FP amounts were 32.9+/-7.3
      microg, 28.9+/-2.4 microg, and 27.1+/-7.9 microg, respectively. In a comparison
      of washing time, the amounts of BDP recovered were 49.8+/-9.7 microg after
      gargling and rinsing for 2 s each, 53.5+/-10.2 microg after those for 3 s each,
      and 47.1+/-13.6 microg after those for 5 s each, while the amounts of FP under
      the same conditions were 36.4+/-2.4 microg, 33.3+/-6.4 microg, and 32.9+/-7.4
      microg, respectively. As for the effect of time lag before mouth washing, the
      amount of BDP recovered decreased by 65.7% with a lag time of 1 min and by 5.6%
      after 10 min, while that of FP decreased by 51.1% with a lag time of 1 min and by
      7.7% after 10 min. Our results suggest that the amount of drugs removed by mouth
      washing is significantly associated with the time lag between inhalation and
      mouth washing. We concluded that immediate gargling and rinsing after inhalation
      is most useful for the removal of drugs following inhalation of corticosteroids.

PMID- 16946511
TI  - Role of tyrosine and tryptophan in chemically modified serum albumin on its
      tissue distribution.
AB  - To investigate the effect of functional groups in bovine serum albumin (BSA) on
      its tissue distribution characteristics, tyrosine (Tyr) or tryptophan (Trp)
      residues of BSA were chemically modified by tetranitromethane (TNM) and 2-hydroxy
      5-nitrobenzyl bromide (HNB), respectively. BSA was successfully modified with
      each reagent depending on the amount of the reagent added to the reaction
      mixture, and TNM- and HNB-modified BSA derivatives with different degrees of
      modification were obtained. Circular dichroism measurements showed that slight
      secondary and large tertiary changes were detectable as the degree of
      modification increased. After intravenous injection into mice, all synthetic BSA
      derivatives were eliminated very slowly from the systemic circulation. However,
      (111)In-TNM(6.6)- and (111)In-HNB(2.0)-BSA, derivatives with a high degree of
      modification, showed a slightly faster disappearance from the systemic
      circulation and slightly higher accumulation in the liver than (111)In-unmodified
      BSA. Pharmacokinetic analyses also demonstrated that the modification of Tyr or
      Trp residues on BSA had only marginal effects on tissue distribution. These
      results indicate that the Tyr and Trp residues have little effect on the tissue
      distribution characteristics of serum albumins, and that the specific
      modification of these residues may be a promising approach to designing sustained
      drug delivery systems using serum albumins.

PMID- 16946512
TI  - Effects of serotonin-3 receptor antagonists on cytochrome P450 activities in
      human liver microsomes.
AB  - The effects of three serotonin-3 (5-HT(3)) receptor antagonists, azasetron,
      ondansetron, and ramosetron, on cytochrome P450 (CYP) 1A2-mediated 7
      ethoxyresorufin O-deethylation, CYP2C9-mediated tolbutamide hydroxylation,
      CYP2C19-mediated S-mephenytoin 4'-hydroxylation, CYP2D6-mediated debrisoquine 4
      hydroxylation, CYP2E1-mediated chlorzoxazone 6-hydroxylation, CYP3A4-mediated
      nifedipine oxidation, and CYP3A4-mediated testosterone 6beta-hydroxylation
      activities in human liver microsomes were compared. Azasetron and ramosetron at a
      concentration of 1 or 10 muM neither inhibited nor stimulated any of the
      metabolic activities. On the other hand, ondansetron competitively inhibited
      CYP1A2 and CYP2D6 activities, and the inhibition constants (K(i)) were 3.2 and
      21.0 muM, respectively, which are much higher than the reported plasma
      concentrations after clinical intravenous or oral dosing. The free fractions of
      the three 5-HT(3) receptor antagonists in the incubation mixture estimated by
      ultracentrifugation were more than 68.6%. These results suggest that azasetron,
      ondansetron, and ramosetron do not cause clinically significant interactions with
      other drugs that are metabolized by CYPs via the inhibition of metabolism.

PMID- 16946513
TI  - Enhancement of anticancer activity in antineovascular therapy is based on the
      intratumoral distribution of the active targeting carrier for anticancer drugs.
AB  - We previously observed the enhanced anticancer efficacy of anticancer drugs
      encapsulated in Ala-Pro-Arg-Pro-Gly-polyethyleneglycol-modified liposome (APRPG
      PEG-Lip) in tumor-bearing mice, since APRPG peptide was used as an active
      targeting tool to angiogenic endothelium. This modality, antineovascular therapy
      (ANET), aims to eradicate tumor cells indirectly through damaging angiogenic
      vessels. In the present study, we examined the in vivo trafficking of APRPG-PEG
      Lip labeled with [2-(18)F]2-fluoro-2-deoxy-D-glucose ([2-(18)F]FDG) by use of
      positron emission tomography (PET), and observed that the trafficking of this
      liposome was quite similar to that of non-targeted long-circulating liposome (PEG
      Lip). Then, histochemical analysis of intratumoral distribution of both liposomes
      was performed by use of fluorescence-labeled liposomes. In contrast to in vivo
      trafficking, intratumoral distribution of both types of liposomes was quite
      different: APRPG-PEG-Lip was colocalized with angiogenic endothelial cells that
      were immunohistochemically stained for CD31, although PEG-Lip was localized
      around the angiogenic vessels. These results strongly suggest that intratumoral
      distribution of drug carrier is much more important for therapeutic efficacy than
      the total accumulation of the anticancer drug in the tumor, and that active
      delivery of anticancer drugs to angiogenic vessels is useful for cancer
      treatment.

PMID- 16946514
TI  - Effect of chitosan on gastrointestinal absorption of water-insoluble drugs
      following oral administration in rats.
AB  - Chitosan is widely used as a dietary weight-loss supplement in Japan. In the
      present study, we examined the effect of chitosan on the gastrointestinal
      absorption profiles of the water-insoluble drugs, indomethacin and griseofulvin,
      and the water-soluble drugs, acetaminophen and cephalexin, after oral
      administration in rats. Rats received oral administration of chitosan (5 mg/kg or
      25 mg/kg) dissolved in 5% acetic acid or vehicle 15 min before oral
      administration of each drug. Chitosan at a dose of 25 mg/kg, but not 5 mg/kg,
      significantly decreased the plasma concentrations of indomethacin and
      griseofulvin after administration as a suspension with a significant delay of the
      time to reach maximum concentration compared to the corresponding control values
      (vehicle-pretreated rats). However, pretreatment of chitosan (25 mg/kg) did not
      change the pharmacokinetics of indomethacin administered as a solution. Further,
      the same dose of chitosan had no effect on the pharmacokinetics of acetaminophen.
      The gastrointestinal absorption profile of an amino-beta-lactam antibiotic,
      cephalexin, which is actively absorbed via carrier-mediated transport system, was
      also unchanged. The present findings at least suggest the possibility that
      chitosan at high dose reduces the gastrointestinal absorption of water-insoluble
      drugs such as indomethacin and griseofulvin, but not water-soluble drugs, by
      diminishing the surfactant-like effect of bile acids.

PMID- 16946515
TI  - Depigmentation of melanocytes by the treatment of extracts from traditional
      Chinese herbs: a cell culture assay.
AB  - OBJECTIVE: To obtain potential skin whitening agents from traditional Chinese
      herbs, we tested changes of melanin content in melanocyte cell lines after
      treatment with extracts of 90 traditional Chinese herbs. METHODS: Mouse
      melanocyte cell lines were used. Depigmentation activity of the herb extracts
      were first screened in Mel-Ab cells, and then re-evaluated in melan-a cells and
      co-culture of melan-a and SP-1 cells. Melanin content and cell viability were the
      two indications for evaluation. Tyrosinase activity and the expression of melanin
      synthesis related enzymes in cells treated with the herb extracts were also
      tested. RESULTS: Nine herb extracts were proved to have depigmentation activity
      similar to or better than that of arbutin and low cytotoxicity to melanocytes.
      Two of them were more effective in co-cultured melan-a cells. Most of the
      effective herb extracts inhibited tyrosinase activity and the expression of
      tyrosinase. Some of them also inhibited tyrosinase related protein-1 and/or
      tyrosinase related protein-2 in cultured cells. CONCLUSIONS: We have found 9 herb
      extracts to be promising skin whitening agents. Among them, water extract of
      Galla Chinensis and ethanol extract of Radix Clematidis exhibited higher
      depigmentation activity and caused lower tyrosinase activity in cell culture
      assays and are worthy to be further studied.

PMID- 16946516
TI  - Responses of the liver to perfluorinated fatty acids with different carbon chain
      length in male and female mice:in relation to induction of hepatomegaly,
      peroxisomal beta-oxidation and microsomal 1-acylglycerophosphocholine
      acyltransferase.
AB  - The potency of the induction of hepatomegaly, peroxisomal beta-oxidation and
      microsomal 1-acylglycerophoshocholine (1-acyl-GPC) acyltransferase was compared
      among perfluorinated fatty acids (PFCAs) with 6-9 carbon chain length in the
      liver of male and female mice. All PFCAs examined induced hepatomegaly and
      peroxisomal beta-oxidation and the potency was in the order of perfluorononanonic
      acid (PFNA), perfluorooctanoic acid (PFOA), perfluoroheptanoic acid (PFHA) and
      perfluorohexanoic acid (PFHeA) when compared with the relative doses to induce
      the two parameters. Microsomal 1-acyl-GPC acyltransferase was induced by PFHA,
      PFOA and PFNA, as was peroxisomal beta-oxidation. No significant sex-related
      difference was observed in the induction of peroxisomal beta-oxidation by any
      PFCAs examined. PFNA and PFOA accumulated in the liver of both male and female
      mice in a dose-dependent manner. PFHA accumulated in the liver to a lesser
      extent; little PFHeA accumulated in the liver. Hepatic concentrations of PFNA,
      PFOA and PFHA were higher in male mice than those in female mice. One linear
      regression line was confirmed between the activities of peroxisomal beta
      oxidation and hepatic concentrations of PFHeA, PFHA, PFOA and PFNA in male mice
      regardless of their carbon chain lengths, and the activities were saturable at
      the concentrations over approximately 500 nmol/g liver. Similar linear regression
      line was obtained between the two parameters in female mice. These results
      suggest (i) that the longer the perfluoroalkyl chain becomes, the more PFCA
      accumulates in the liver of both male and female mice, (ii) that the accumulated
      PFCAs induce hepatomegaly, peroxisomal beta-oxidation and microsomal 1-acyl-GPC
      acyltransferase, and (iii) that the difference observed in the accumulation of
      PFHA, PFOA and PFNA in the liver between male and female mice is not enough to
      produce obvious sex-related difference in the induction of peroxisomal beta
      oxidation.

PMID- 16946517
TI  - Enhancement of de novo fatty acid biosynthesis in hepatic cell line Huh7
      expressing hepatitis C virus core protein.
AB  - Hepatitis C virus (HCV) core protein plays important roles in the pathogeneses of
      liver steatosis as well as hepatocellular carcinomas due to HCV infection. In
      this study, we examined de novo fatty acid biosynthesis in hepatic cell line Huh7
      cells expressing HCV core protein. The rate of metabolic labeling of cellular
      fatty acids with [(3)H]acetate in core-expressing (Uc39-6) cells was ca. 1.5-fold
      higher than that in non-expressing (Uc321) cells. The enzyme activities
      responsible for fatty acid biosynthesis were assayed in vitro. Cytosolic acetyl
      CoA carboxylase activity in Uc39-6 cells was ca. 1.6-fold higher than that in
      Uc321 cells. On the other hand, cytosolic fatty acid synthase activity in Uc39-6
      cells was only slightly higher than that in Uc321 cells. Immunoblot analysis of
      acetyl-CoA carboxylase 1 (ACC1), which is a rate-limiting enzyme for fatty acid
      biosynthesis, revealed a higher expression level of the protein in Uc39-6 cells
      than in Uc321 cells. The ACC1 mRNA content in Uc39-6 cells was 1.4-fold higher
      than that in Uc321 cells. These results strongly suggest that enhancement of
      fatty acid biosynthesis in core-expressing cells is caused by increased
      expression of fatty acid biosynthetic enzymes, especially ACC1. Up-regulation of
      de novo fatty acid biosynthesis by HCV core protein may affect cellular lipid
      metabolism, resulting in neutral lipid accumulation in HCV-infected cells.

PMID- 16946518
TI  - Dynamics of mitochondria during the cell cycle.
AB  - Mitochondria are highly dynamic organelles in eukaryotic cells. Although the role
      of mitochondria in metabolism, ATP production and apoptosis is more widely
      recognized, alterations in mitochondrial morphology and abundance are also
      important for cellular functions. Here we investigated mitochondrial dynamics in
      synchronized HeLa cells in which the major stages of the cell cycle of the
      observed cells were resolved by staining phosphorylate histones H1 and H3, and
      showed that mitochondria exist as filamentous network structures throughout the
      cell cycle progression, changing their morphology, distribution, and abundance.
      The current results suggest that mitochondrial condensation occurred at prophase
      is required for the proper progression of mitochondrial division.

PMID- 16946519
TI  - Inhibitory effect of artocarpanone from Artocarpus heterophyllus on melanin
      biosynthesis.
AB  - In our previous efforts to find new tyrosinase inhibitory materials, we
      investigated 44 Indonesian medicinal plants belonging to 24 families. Among those
      plants, the extract of Artocarpus heterophyllus was one of the strongest
      inhibitors of tyrosinase activity. By activity-guided fractionation of A.
      heterophyllus wood extract, we isolated artocarpanone, which inhibited both
      mushroom tyrosinase activity and melanin production in B16 melanoma cells. This
      compound is a strong candidate as a remedy for hyperpigmentation in human skin.

PMID- 16946520
TI  - Melanogenesis inhibitory and free radical scavenging activities of
      diarylheptanoids and other phenolic compounds from the bark of Acer nikoense.
AB  - Melanogenesis inhibitory and free radical scavenging activities of nine cyclic (1
      9) and one acyclic diarylheptanoids (10), and two phenolic compounds, (+)
      rhododendrol (11) and (+)-catechin (12), isolated from the ethyl acetate-soluble
      fraction of the MeOH extract of the bark of Acer nikoense MAXIM. (Aceraceae) were
      examined. Upon evaluation of compounds 1-12 on the melanogenesis in the B16
      melanoma cells, two compounds, 2 and 8, exhibited marked inhibitory activity with
      55.6% and 46.8% reduction, respectively, of melanin content at 25 microg/ml
      without inhibition of cell proliferation. In addition, upon an evaluation of
      eleven compounds, 1-7 and 9-12 against the scavenging activities of free radicals
      (against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical), compound 12 (IC(50)
      9.0 microgM) followed by compounds 1, 3, 4, and 6 (IC(50) 40.2-44.0 microgM)
      showed potent scavenging activities.

PMID- 16946521
TI  - Pharmacological properties of traditional medicine (XXXII): protective effects of
      hangeshashinto and the combinations of its major constituents on gastric lesions
      in rats.
AB  - The protective effect of Hangeshashinto (HST) and its major constituents,
      baicalin (BA), berberine (BE), saponin fraction of ginseng (GS) and glycyrrhizin
      (GL) on rat gastric lesion induced by ethanol was examined to clarify its active
      ingredients and action mechanism. Oral treatment with HST at the doses of 125 and
      250 mg/kg suppressed ethanol-induced gastric lesions. The mixture of BA, BE, GL
      and GS (4M), each of BE, GL and GS at the dosage corresponded to HST (125 mg/kg)
      also suppressed the ethanol-induced gastric lesion in rats, but BA did not.
      Treatment of ethanol augmented the activity of myeloperoxidase (MPO) in the
      stomach, which was significantly suppressed by the administration of HST, BE, GL
      and GS. These results suggest that the protective effect of HST on ethanol
      induced gastric lesion was depended on BE, GL and GS, by, in part, the reduction
      of MPO activity in stomach.

PMID- 16946522
TI  - Cancer chemopreventive effects and cytotoxic activities of the triterpene acids
      from the resin of Boswellia carteri.
AB  - Fifteen triterpene acids, viz., seven of the beta-boswellic acids (ursane-type)
      (1-7), two of the alpha-boswellic acids (oleanane-type) (8, 9), two of the
      lupeolic acids (lupane-type) (10, 11), and four of the tirucallane-type (12-14,
      16), and two cembrane-type diterpenes (17, 18), isolated from the MeOH extract of
      the resin of Boswellia carteri (Burseraceae), together with a triterpene acid 15
      (the acetyl derivative of 14), were examined for their inhibitory effects on the
      induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O
      tetradecanoylphorbol-13-acetate (TPA) in Raji cells and on activation of (+/-)
      (E)-methyl-2[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitrogen
      oxide (NO) donor, and cytotoxic activities against three human neuroblastoma cell
      lines, IMR-32, NB-39, and SK-N-SH in vitro. On evaluation against the EBV-EA
      activation induced by TPA, seven compounds, 2, 10, 11, and 13-16, showed potent
      inhibitory effects on EBV-EA induction. Upon evaluation against activation of NOR
      1, five compounds, 7, 13, and 14-16, showed potent inhibitory effects. Further,
      fifteen compounds, 1-7, 9-11, 13-15, 17, and 18, exhibited potent cytotoxic
      activities with IC(50) values of 4.1-82.4 muM against all of the three human
      neuroblastoma cells tested.

PMID- 16946523
TI  - Inhibitory activities of plastoquinones and chromene derivative from a brown alga
      Sagassum micracanthum on bone resorption.
AB  - We evaluated inhibitory effects of plastoquinones (1, 2) and chromene derivative
      (3) from the methanol extract of Sargassum micracanthum on the differentiation of
      osteoclast progenitors into osteoclast-like cells (OCLs), bone-resorbing activity
      and the survival of OCLs. When OCL formation was investigated using osteoclast
      progenitor cells obtained from macrophage-colony stimulating factor (M-CSF)
      treated mouse bone marrow, 1-3 inhibited dose-dependently OCL formation at the
      concentrations of 3-10 muM, the order of inhibitory potency being 1>3>2. In
      addition, they suppressed dose-dependently the pit formation induced by OCL on
      dentine slices, the order of inhibitory potency being 1>3>2. The survival of OCLs
      was inhibited by about 35, 45 and 60% in the presence of 6 muM of 2, 3 and 1,
      respectively. These results suggest that the inhibitory effects of the three
      compounds on the differentiation, pit formation and the survival of OCLs might
      contribute to the suppression of bone resorption.

PMID- 16946524
TI  - Effect of glimepiride and glibenclamide on S-warfarin 7-hydroxylation by human
      liver microsomes, recombinant human CYP2C9.1 and CYP2C9.3.
AB  - The effect of glimepiride on metabolism of S-warfarin to 7-hydroxywarfarin was
      studied using human liver microsomes and recombinant cytochrome P450 2C9
      microsomes (CYP2C9.1 and CYP2C9.3), and was compared with the results from the
      experiments using glibenclamide as an inhibitor. S-Warfarin 7-hydroxylation by
      recombinant CYP2C9.1 and CYP2C9.3 was inhibited by glimepiride competitively. The
      apparent K(i) value of glimepiride was lower at CYP2C9.3 than at CYP2C9.1.
      Glimepiride also inhibited 7-hydroxylation of S-warfarin in a competitive manner
      by microsomes from human liver which showed the genotypes of CYP2C9, as
      CYP2C9*1/*1 or CYP2C9*1/*3. The apparent K(i) value of glimepiride was lower than
      that of glibenclamide. These results may provide valuable information for
      optimizing the anticoagulant activity of warfarin when glimepiride is co
      administered to patients.

PMID- 16946525
TI  - Intracellular trafficking is the important process that determines the optimal
      charge ratio on transfection by galactosylated lipoplex in HEPG2 cells.
AB  - The purpose of the present study was to gain insight into the major factors
      affecting transfection efficiency with galactosylated lipoplex in HepG2 cells. In
      this study, lipoplex and galactosylated lipoplex were examined at different
      charge ratios (- : +): 1.0 : 1.2, 1.0 : 2.3, 1.0 : 3.1, 1.0 : 4.7, and 1.0 : 7.0.
      The particle size and zeta potential of the both lipoplexes was dependent on the
      charge ratio. Cellular uptake was evaluated by using [(32)P]-labeled pCMV-Luc and
      this showed that the cellular uptake of galactosylated lipoplex was significantly
      higher than that of lipoplex at a charge ratio ranging from 1.0 : 2.3 to 1.0 :
      7.0. As the charge ratio increased in both lipoplexes, the apparent cellular
      uptake increased. Transfection activity by galactosylated lipoplex was
      significantly higher than that by lipoplex except at a charge ratio of 1.0 : 7.0.
      The optimal charge ratio for transfection efficacy was 1.0 : 2.3 and transfection
      was reduced at higher charge ratios. Both lipoplexes exhibited no significant
      cytotoxicity at any charge ratio. In conclusion, it is suggested that
      intracellular trafficking, rather than the degree of uptake and cytotoxicity, is
      the important process that determines the optimal charge ratio of galactosylated
      lipoplex in HepG2 cells.

PMID- 16946526
TI  - Guaianolides from Salvia nubicola (Lamiaceae).
AB  - A new sesquiterpene-lactone (nubenolide) belonging to the guaianolide class along
      with its acetate (nubenolide acetate) and a dimer (bisnubenolide) have been
      isolated from Salvia nubicola collected from Quetta, Pakistan. Structures of all
      three new metabolites were elucidated with the aid of spectroscopic techniques
      including 2D-NMR. However, the structure of nubenolide was finally confirmed via
      single-crystal X-ray diffraction method.

PMID- 16946527
TI  - Study of the interaction of indirubin with bovine serum albumin.
AB  - This study examined the interaction of indirubin with bovine serum albumin (BSA)
      at three temperatures (286, 297, 308 K) at pH 7.40. In the presence of indirubin,
      the drug-BSA binding mode, binding constant and the protein structure changes in
      aqueous solution were determined by fluorescence quenching methods including
      Fourier transform infrared (FT-IR) spectroscopy and UV-Vis spectroscopy. The FT
      IR change indicates that indirubin binds to BSA. The change in protein secondary
      structure accompanying ligand binding has been proved by fluorescence spectra
      data. The thermodynamic parameters, the enthalpy change (DeltaH), and the entropy
      change (DeltaS) calculated by the van't Hoff equation possess small negative (
      2.744 kJ.mol(-1)) and positive values (112.756 J.mol(-1).K(-1)), respectively,
      which indicated that hydrophobic interactions play the main role in the binding
      of indirubin to BSA. Furthermore, the displacement experiment shows that
      indirubin can bind to the subdomain IIA and the distance between the tryptophan
      residues in BSA and indirubin bound to site I was estimated to be 2.24 nm
      according to Foster's equation on the basis of fluorescence energy transfer.

PMID- 16946528
TI  - Prediction of granule physical property by a novel compression energy of wet
      powder.
AB  - Wet granulation is a very important process and a reliable evaluation method for
      formulation study; thus it requires appropriate process control. In this study, a
      novel and effective method that involves a compression test of wet powder is
      proposed. Here, the compression energy, which could predict the capability of the
      wet powder for extrusion granulation as well as the physical properties of the
      final products, is used as a novel characteristic of wet powder. The compression
      energy was defined as the energy consumption derived from the compression speed
      and the transmission loss during the compression test. Lactose monohydrate was
      mixed with various additives such as hydroxypropylcellulose in the mass ratio of
      0-10%. Various amounts of water were fed into the mixtures, which were kneaded in
      a planetary motion mixer to prepare the kneaded wet powders. The characteristics
      of these powders were evaluated by the compression energy. The kneaded wet
      powders were then extruded through an extrusion granulator, the electrical loads
      of the granulator during the operation were analyzed as the extrusion energy, and
      the physical properties of extruded granules were investigated. As a result, the
      granule strength and granule size distribution showed a good correlation with the
      compression energy. A good correlation was also observed between the compression
      energy of the kneaded wet powder and the extrusion energy regardless of the
      different additives and water contents. It was concluded that the compression
      energy of the wet powder could be used for the formulation study and the process
      control of wet granulation.

PMID- 16946529
TI  - Non-nucleoside HIV-1 reverse transcriptase inhibitors, Part 7. Synthesis,
      antiviral activity, and 3D-QSAR investigations of novel 6-(1-naphthoyl) HEPT
      analogues.
AB  - A series of novel 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT)
      analogues bearing a 6-(1-naphthoyl) group of non-nucleoside human
      immunodeficiency virus (HIV) reverse transcriptase inhibitors were synthesized
      and evaluated for their activity against HIV-1 and HIV-2. It was found that most
      of these compounds showed good activity against HIV-1. Among them, compound 5
      isopropyl-6-(1-naphthoyl)-1-[(2E)-3-phenylallyl]-2,4-pyrimidinedione (23)
      displayed the greatest inhibitory potency (IC(50)=0.14 muM), which is about 35
      fold more active than HEPT and DDI. To rationalize the relationships between
      structure and activity of these novel compounds, a three-dimensional quantitative
      structure-activity relationship (3D-QSAR) model was also generated. The results
      provided a tool for guiding the further design of more potent antiviral agents
      and for predicting the affinity of related compounds.

PMID- 16946530
TI  - Gene delivery into brain capillary endothelial cells using Antp-modified DNA
      loaded nanoparticles.
AB  - Our aim is to test the characteristics and expression activity in brain capillary
      endothelial cells (BCECs) of DNA-loaded nanoparticles before and after the
      modification with Antennapedia peptide (Antp). Chitosan (CH), polyethylenimine
      (PEI) and polyamidoamine (PAMAM) were chosen to prepare the nanoparticles;
      Lipofectamine 2,000 served as control. The incorporation efficiency was
      determined by agarose gel electrophoresis and PicoGreen assay. Transmission
      electron microscopy was performed to observe the diameter. The expression
      efficiency was qualified with fluorescence microscopy and quantified with the
      luciferase assay system. Heparin and DNase I were employed to investigate the
      stability. The results indicated that the gene products of DNA/CH nanoparticles
      and DNA/Lipofectamine 2,000 complexes whether modified or unmodified with Antp
      could not be observed within BCECs. The DNA/PEI nanoparticles and DNA/PAMAM
      nanoparticles could be internalized into BCECs to a certain extent, and the
      expression efficiency was enhanced significantly with the modification of Antp.
      The diameter increased from 100 to 200 nm after modification with Antp. The
      nanoparticles could protect themselves from the displacement of anionic
      substances and the digestion of DNase I. These observations demonstrated that
      Antp, polymer and DNA could form stable nanoparticles, and the modification of
      Antp can enhance the expression efficiency of DNA-loaded nanoparticles in BCECs.

PMID- 16946531
TI  - Biodegradable PLGA microspheres as a sustained release system for a new
      luteinizing hormone-releasing hormone (LHRH) antagonist.
AB  - A sustained release poly(DL-lactide-co-glycolide) (PLGA) microsphere delivery
      system to treat prostate cancer for a luteinizing hormone-releasing hormone
      (LHRH) antagonists, LXT-101 was prepared and evaluated in the paper. LXT-101
      microspheres were prepared from PLGA by three methods: (1) double-emulsion
      solvent extraction/evaporation technique, (2) single-emulsion solvent
      extraction/evaporation technique, and (3) S/O/O (solid-in-oil-in-oil) method. The
      microspheres were investigated on drug loading, particle size, surface morphology
      and in vitro release profiles. An accelerated release approach was also
      established in order to expedite the evaluation periods. The in vivo evaluation
      of the microspheres was made by monitoring testosterone levels after subcutaneous
      administration to rats. The LXT-101 PLGA microspheres showed smooth and round
      surfaces according to a scanning electron microscopic investigation, and average
      particle size of ca. 30 mum according to laser diffractometry. The drug
      encapsulation efficiency of microspheres was influenced by LA/GA ratio of PLGA,
      salt concentrations, solvent mixture and preparation methods. Moreover, LA/GA
      ratio of PLGA, different preparation methods and different peptide stabilizers
      affected in vitro release of drugs. In vivo study, the testosterone levels were
      suppressed to castration up to 42 d as for the 7.5 mg/kg dose. And in vivo
      performance of LXT-101 microspheres was dose-dependent. The weights of rat sexual
      organs decreased and histopathological appearance of testes had little changes
      after 4-month microspheres therapy. This also testified that LXT-101 sustained
      release microspheres could exert the efficacy to suppress the testosterone level
      to castration with little toxicity. In conclusion, the PLGA microspheres could be
      a well sustained release system for LXT-101.

PMID- 16946532
TI  - Inhibitory effect of ammonium tetrathiotungstate on tyrosinase and its kinetic
      mechanism.
AB  - Tyrosinase requires two copper ions at the active site, in order to oxidize
      phenols to catechols. In this study, the inhibitory effect of the copper
      chelating compound, ammonium tetrathiotungstate (ATTT), on the tyrosinase
      activity was investigated. ATTT was determined to inactivate the activity of
      mushroom tyrosinase, in a dose-dependent manner. The kinetic substrate reaction
      revealed that ATTT functions as a kinetically competitive inhibitor in vitro, and
      that the enzyme-ATTT complex subsequently undergoes a reversible conformational
      change, resulting in the inactivation of tyrosinase. In human melanin-producing
      cells, ATTT evidenced a more profound tyrosinase-inhibitory effect than has been
      seen in the previously identified tyrosinase inhibitors, including kojic acid and
      hydroquinone. Our results may provide useful information for the development of
      whitening agent.

PMID- 16946533
TI  - Quality evaluation of cortex moutan by high performance liquid chromatography
      coupled with diode array detector and electrospary ionization tandem mass
      spectrometry.
AB  - An high performance liquid chromatography (HPLC) coupled with diode array
      detector (DAD) and electrospray ionization tandem mass spectrometry (ESI/MS(n))
      method was developed for quality evaluation of Cortex Moutan through
      identification of common constituents based on chromatographic fingerprints and
      determination of key pharmacological compounds. The representative
      chromatographic fingerprints of Cortex Moutan were obtained by analyzing 10
      batches of samples under the optimized HPLC conditions and the results showed
      that the chromatographic profiles of the analyzed samples were very similar.
      Total of nineteen common peaks were detected and seventeen of them were
      identified rapidly by their characteristic UV profile and the information of
      molecular structure provided by ESI/MS(n) experiments. Simultaneously, five key
      pharmacological compounds, namely gallic acid, oxypaeoniflorin, paeoniflorin,
      benzoylpaeoniflorin and paeonol, were determined by the validated HPLC-DAD
      method. The linear calibration curves were acquired with correlation coefficients
      higher than 0.999. The precisions of intra-day and inter-day were not exceeding
      3.1%, and the recoveries of five analytes were from 92.86 to 99.35%. This
      developed method that combined the chromatographic fingerprints and
      quantification assay ensured the phytoequivalence and pharmacological effects of
      Cortex Moutan and was successfully applied to the quality control of Cortex
      Moutan.

PMID- 16946534
TI  - Effect of the moisture content in aerosol on the spray performance of Stmerin D
      HFA preparations.
AB  - Stmerin D, a pressurized metered dose inhaler (MDI) for treatment of asthma,
      contains CFCs (chlorofluorocarbons) as a propellant. For the CFC replacement
      study, two formulations were prepared using hydrofluoroalkanes (HFA-134a and HFA
      227) and the effect of storage on the spray performance was investigated under
      accelerated stress conditions. Drug stability, moisture content and spray
      performances such as the emitted dose uniformity and aerodynamic particle size
      distribution were evaluated. Drug content did not change after 3 months storage
      at 40 degrees C/75% RH. However, the emitted dose uniformity varied and the
      respirable fraction (RF) was reduced remarkably. While stored at 40 degrees
      C/ambient for 3 months, no change was observed in either drug content or spray
      performances. This study clarified that the moisture content in the canister
      played an important role on the spray performance, and it changed not only the
      emitted dose uniformity but also the particle size distribution. Consequently, in
      order to improve the stability of the spray performance of aerosol prepared with
      HFAs, moisture permeation into the canister must be controlled.

PMID- 16946535
TI  - Syntheses of new model compounds related to an antigenic epitope from Bupleurum
      falcatum L. and their distributions in various ganglioside-phospholipid
      monolayers.
AB  - 6-N-[2-(Tetradecyl)hexadecanamido]hexyl beta-D-glucopyranosyluronic acid-(1-->6)
      beta-D-galactopyranosyl-(1-->6)-beta-D-galactopyranoside (1) and its clustering
      compound (2) carrying a tetravalent sugar unit, which are new model compounds
      related to a major antigenic epitope from antiulcer pectic polysaccharide of
      Bupleurum falcatum L., were synthesized and the distributions of 1 and 2 in mixed
      ganglioside (GM1, GD1a or GT1b)/phospholipid (DPPC) monolayers were observed
      using atomic force microscopy (AFM). AFM images showed that 1 was distributed in
      the GM1, GD1a and GT1b region of the mixed monolayers, in which 1 was miscible
      with GD1a. Specific distribution of 1 was observed in the mixed GM1/DPPC
      monolayer. Compound 2 was miscible with GM1, while 2 formed associations with
      GD1a and GT1b in the mixed monolayers. The distribution mode of 1 and 2 was
      different among the mixed ganglioside/DPPC monolayers.

PMID- 16946536
TI  - New A-ring lactone triterpenoid saponins from the roots of Platycodon
      grandiflorum.
AB  - Three new A-ring lactone triterpenoid saponins, platycoside M-1 [3-O-beta-D
      glucopyranosyl platycogenic acid A lactone], platycoside M-2 [3-O-beta-D
      glucopyranosyl platycogenic acid A lactone 28-O-alpha-L-rhamnopyranosyl-(1-->2)
      alpha-L-arabinopyranoside], and platycoside M-3 [3-O-beta-D-glucopyranosyl
      platycogenic acid A lactone 28-O-beta-D-xylopyranosyl-(1-->4)-alpha-L
      rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside], were isolated from the roots
      of Platycodon grandiflorum A. DC. Their chemical structures were elucidated on
      the basis of their spectral data and chemical evidence.

PMID- 16946537
TI  - Bitterness suppression of BCAA solutions by L-ornithine.
AB  - The purpose of the present study was to evaluate the bitterness-suppressing
      effect of L-ornithine (L-Orn) on single or mixed solutions of branched-chain
      amino acids (BCAAs) using human gustatory sensation tests and an artificial taste
      sensor. The BCAAs tested (L-isoleucine (L-Ile), L-leucine (L-Leu), and L-valine
      (L-Val)) are the main components of various enteral nutrients or supplements. The
      bitterness-suppression effect of L-Orn was also compared with the effect of L
      Arg. L-Orn was effective in suppressing the bitterness of single or mixed
      solutions of BCAAs in human gustatory sensation tests, the effect being similar
      to or greater than that of L-Arg. The artificial taste sensor was able to predict
      the bitterness-suppressing effects of L-Orn and L-Arg. The response electric
      potential patterns of L-Val, L-Leu and L-Ile solutions to which 100 mM L-Arg had
      been added were quite similar to the sensor response patterns of the 100 mM L-Arg
      solutions alone. The relative response electric potential patterns of L-Val, L
      Leu or L-Ile solutions containing 100 mM L-Orn in channels 5-8 (positively
      charged) are similar to that of single solution of 100 mM L-Orn.

PMID- 16946538
TI  - Constituents of Holothuroidea, 18. Isolation and structure of biologically active
      disialo- and trisialo-gangliosides from the sea cucumber Cucumaria echinata.
AB  - Three new disialo- and trisialo-gangliosides, CEG-6 (6), CEG-8 (8), and CEG-9
      (9), were obtained, together with one known ganglioside, HLG-3 (7), from the
      lipid fraction of the chloroform/methanol extract of the sea cucumber Cucumaria
      echinata. The structures of the new gangliosides were determined on the basis of
      chemical and spectroscopic evidence to be 1-O-[alpha-L-fucopyranosyl-(1-->11)-(N
      glycolyl-alpha-D-neuraminosyl)-(2-->4)-(N-acetyl-alpha-D-neuraminosyl)-(2-->6)
      beta-D-glucopyranosyl]-ceramide (6) and 1-O-[(N-glycolyl-D-neuraminosyl)-(2-->11)
      (N-glycolyl-D-neuraminosyl)-(2-->4)-(N-acetyl-D-neuraminosyl)-(2-->6)-D
      glucopyranosyl]-ceramide (8, 9). The ceramide moieties of each compound were
      composed of an homogeneous sphingosine or phytosphingosine base and heterogeneous
      2-hydroxy or nonhydroxylated fatty acid units. These gangliosides showed
      neuritogenic activity toward the rat pheochromocytoma cell line PC-12 in the
      presence of nerve growth factor.

PMID- 16946539
TI  - Investigation of selective mono-deallylation of O,O'-diallylcatechols and 3
      methylene-1,5-benzodioxepanes.
AB  - Selective mono-deallylation of O,O'-diallylcatechols using 10% Pd/C was
      investigated to give the correspond-ing allylphenols. A similar reaction of 3
      methylene-1,5-benzodioxepanes afforded O-methacryl catecohols. When substrates
      bearing various substituents on the benzene ring were subjected to the reaction,
      regioselective cleavage of an ether bond occurred at the side of para position to
      an electron-withdrawing group on the aromatic ring. On the other hand, an
      electron-donating group did not cause any selectivity.

PMID- 16946540
TI  - Study on the reactivity of diarylmethane derivatives in supercritical alcohols
      media: reduction of diarylmethanols and diaryl ketones to diarylmethanes using
      supercritical 2-propanol.
AB  - We found that diarylmethanols and diaryl ketones were smoothly reduced to the
      corresponding diarylalkanes using supercritical 2-propanol in good yields.
      Furthermore, we determined the specific reaction of fluorene using supercritical
      methanol at high temperature.

PMID- 16946541
TI  - Constituents from the leaves of Phellodendron amurense and their antioxidant
      activity.
AB  - Three new coumarins, phellodenols F-H (1-3) and a new glutaric acid derivative,
      phellodendric acid-A (4) were isolated from the leaves of Phellodendron amurense
      together with twenty-nine known compounds. Extensive 1D and 2D NMR experiments
      and other spectroscopic studies were employed to determine the structures of 1-4.
      The isolated compounds were screened for their antioxidant activity through DPPH
      (alpha,alpha-diphenyl-beta-picrylhydrazyl) radical scavenging assay. Compounds
      quercetin, quercetin-3-O-beta-D-glucoside, quercetin-3-O-beta-D-galactoside and
      kaempferol-3-O-beta-D-glucoside demonstrated significant radical scavenging
      activity comparable to vitamin E.

PMID- 16946542
TI  - Metabolism of tomato steroidal glycosides in humans.
AB  - Pregnane glycosides have been isolated in small amounts, along with the major
      components furostanol and spirostanol glycosides, from Dioscoreaceae, Taccaceae,
      and Solanaceae, suggesting that pregnane glycosides might be biosynthesized from
      furostanol and spirostanol glycosides. Recently, commercial natural foods
      composed of diosgenin have been used for the treatment of diseases such as
      osteoporosis and premenstrual syndrome in women. It is anticipated that diosgenin
      would be metabolized into a type of steroidal hormone, for instance progesterone,
      however, this metabolism has not been confirmed. Therefore, we have examined the
      metabolites in the urine of subjects who ingested tomatoes, which contain a
      considerable amount of the steroidal glycoside esculeoside A. The occurrence of
      steroidal hormones in the metabolites has been recognized. It has been proven
      that when a steroidal glycoside is administered, it is partly metabolized into a
      type of steroidal hormone exhibiting various physiological activities.

PMID- 16946543
TI  - Puerariafuran, a new inhibitor of advanced glycation end products (AGEs) isolated
      from the roots of Pueraria lobata.
AB  - A new 2-arylbenzofuran, puerariafuran (1), as well as three known compounds,
      coumestrol (2), daidzein (3), and genistein (4), were isolated from a MeOH
      extract of the roots of Pueraria lobata as active constituents, using an in vitro
      bioassay based on the inhibition of advanced glycation end products (AGEs) to
      monitor chromatographic fractionation. The structure of 1 was determined by
      spectroscopic data interpretation, particularly by extensive 1D and 2D NMR
      studies. All the isolates (1-4) were evaluated for the inhibitory activity on
      AGEs formation in vitro.

PMID- 16946544
TI  - Major metabolites of zolpidem: expeditious synthesis and mass spectra.
AB  - An expeditious route to the two major metabolites of Zolpidem-and readily
      applicable to the synthesis of the drug-was established via a cyclization
      reaction between a 2-aminopyridine and a suitable alpha-bromoacetophenone. The
      structures of the target compounds were confirmed from a 2D (1)H-(15)N NMR
      correlation. Their mass spectra contribute to a reliable toxicological
      identification of the drug in the case of drug-facilitated crimes.

PMID- 16946545
TI  - Two new 15-deoxycimigenol-type and three new 24-epi-cimigenol-type glycosides
      from Cimicifuga Rhizome.
AB  - Two new 15-deoxycimigenol-type (1, 2) and three new 24-epi-cimigenol-type
      glycosides (3-5) were isolated from Cimicifuga Rhizome, and the structures were
      elucidated on the basis of spectroscopic data including 2D NMR spectra and
      chemical evidence. The two new 15-deoxycimigenol-type glycosides were the first
      cimigenol-type glycosides lacking a hydroxyl group at C-15.

PMID- 16946546
TI  - SAR study of 1-aryl-4-(phenylarylmethyl)piperazines as ligands for both dopamine
      D2 and serotonin 5-HT1A receptors showing varying degrees of (Ant)agonism.
      Selection of a potential atypical antipsychotic.
AB  - The syntheses of several 1-aryl-4-(arylpyridylmethyl)piperazines (4) and their
      affinities for dopamine D(2) and serotonin 5-HT(1A) receptors are described. The
      compounds were evaluated both in vitro and in vivo, resulting in the
      identification of the drug candidate SLV313 (4e) with equipotent and full D(2)
      receptor antagonism and 5-HT(1A) receptor agonism. Minor structural modifications
      in SLV313 revealed the possibility of designing compounds possessing varying
      degrees of partial agonism on one or both target receptors.

PMID- 16946547
TI  - A convenient preparation of (1R,2S,7S,8R)-3,5-diaza-2,7-dimethyl-1,8
      diphenyloctan-1,8-diol and its enantiomer.
AB  - The synthesis of (1R,2S,7S,8R)-3,5-diaza-2,7-dimethyl-1,8-diphenyloctan-1,8-diol
      6 and its enantiomer 7 are described utilising (-)-(1R,2S)- or (+)-(1S,2R)
      norephedrine, respectively.

PMID- 16946548
TI  - Asymmetric synthesis of methyl (-)-13-oxo-15,16-dinorlabda-8(17),11E-dien-19
      oate, methyl ester of a potent suppressor toward carcinogenic promotor.
AB  - Asymmetric synthesis of methyl ester (4) of (-)-13-oxo-15,16-dinorlabda-8(17),11E
      dien-19-oic acid (1), which exhibited the most potent activity for the prevention
      of incipient carcinogenesis among the isolated diterpenes from Thuja standishii
      and its related plants, was achieved by using methyl (-)-1,4a-dimethyl-5
      oxodecahydronaphthalene-1-carboxylate (5) as a strating material, which was
      easily prepared on gram scale by baker's yeast-catalyzed asymmetric reduction.

PMID- 16946549
TI  - Polystachyne F, a 5,10-seco-neoclerodane from Salvia polystachya.
AB  - A new 5,10-seco-neoclerodane diterpene, polystachyne F (1), was isolated from the
      aerial parts of Salvia polystachya. Its structure was established on the basis of
      its spectroscopic properties and X-ray crystallographic analysis. Some
      correlations in the NOESY spectrum of 1 suggested the existence of a
      conformational equilibrium.

PMID- 16946550
TI  - An approach for decontamination of beta-lactam antibiotic residues or
      contaminants in the pharmaceutical manufacturing environment.
AB  - An effective procedure for decontamination of beta-lactam antibiotic residues or
      contaminants in the pharmaceutical manufacturing environment was investigated.
      Decontamination with solutions of hydrochloric acid, sodium hydroxide, hydrogen
      peroxide and hydroxylamine as agents for degradation was assessed. According to
      the results, the beta-lactam antibiotics were significantly degraded with sodium
      hydroxide and hydroxylamine. From the structural analysis of the degradation
      products of a cephem antibiotic, cefpodoxime proxetil, it was found that
      hydroxylamine degraded the beta-lactam structure under mild conditions, while
      sodium hydroxide did not. Therefore, hydroxylamine was considered an appropriate
      decontamination agent for beta-lactam antibiotics.

PMID- 16946551
TI  - Potent cytotoxic rocaglamide derivatives from the fruits of Amoora cucullata.
AB  - Two new rocaglamide derivatives, 1-O-formylrocagloic acid (1) and 3'-hydroxy
      rocagloic acid (2), together with five known compounds, rocaglaol (3), rocagloic
      acid (4), 3'-hydroxymethylrocaglate (5), 1-O-formylmethyl rocaglate (6), and
      methylrocaglate (7), were isolated from the fruits of Amoora cucullata. Their
      structures were elucidated by spectroscopic methods. Compounds 1-3, 6, and 7
      exhibited potent cytotoxicity against KB, BC, and NCI-H187 cell lines, whereas 4
      and 5 showed selective cytotoxicity against NCI-H187 cell line.

PMID- 16946552
TI  - Bazzanane sesquiterpenoids from the New Zealand liverwort Frullania falciloba.
AB  - Two new bazzanane-type sesquiterpenoids have been isolated from the New Zealand
      liverwort Frullania falciloba. Their structures were confirmed by NMR and CD
      spectroscopy and chemical reactivity.

PMID- 16946553
TI  - Xenobiotic-metabolizing enzymes involved in activation and detoxification of
      carcinogenic polycyclic aromatic hydrocarbons.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental carcinogens
      and metabolized by a variety of xenobiotic-metabolizing enzymes such as
      cytochrome P450 (P450 or CYP), epoxide hydrolase, glutathione transferase, UDP
      glucuronosyltransferase, sulfotransferase, NAD(P)H quinone oxidoreductase 1, and
      aldo-keto reductase. These enzymes mainly participate in the conversion of PAHs
      to more polar and water-soluble metabolites, and the resultant metabolites are
      readily excreted from the body. However, during the course of metabolism, a
      variety of unstable and reactive intermediates of PAHs are formed, and these
      metabolites attack DNA, causing cell toxicity and transformation. P450s and
      epoxide hydrolase convert PAHs to proximate carcinogenic metabolites, PAH-diols,
      and these products are further metabolized by P450s to ultimate carcinogenic
      metabolites, PAH diol-epoxides, or by aldo-keto reductase to reactive PAH o
      quinones. PAHs are also activated by P450 and peroxidases to reactive radical
      cations that bind covalently to DNA. The oxygenated and reactive metabolites of
      PAHs are usually converted to more polar and detoxified products by phase II
      enzymes. Inter-individual differences exist in levels of expression and catalytic
      activities of a variety of enzymes that activate and/or detoxify PAHs in various
      organs of humans and these phenomena are thought to be critical in understanding
      the basis of individual differences in response to PAHs. Factors affecting such
      variations include induction and inhibition of enzymes by diverse chemicals and,
      more importantly, genetic polymorphisms of enzymes in humans.

PMID- 16946555
TI  - CYP2C19 genetic polymorphism in Thai, Burmese and Karen populations.
AB  - The genetic polymorphism of CYP2C19 was examined in three Southeast Asian
      populations. This study was conducted in 774 Thais, 127 Burmeses and 131 Karens.
      Genomic DNA was extracted from leucocytes and analyzed by the PCR-RFLP technique.
      Genotype analysis revealed that the allele frequencies of CYP2C19*1, CYP2C19*2
      and CYP2C19*3 in the Thais were 0.68, 0.29 and 0.03, respectively, and those of
      the Burmese population were 0.66, 0.30 and 0.04, respectively. For Karens, the
      minority ethnic in Mynmar, the allele frequencies of CYP2C19*1, CYP2C19*2 and
      CYP2C19*3 were 0.71, 0.28 and 0.01, respectively. The prevalence of PM estimated
      from genotype data among these three ethnic populations were 9.2%, 11.0%, and
      8.4%, respectively. The PM phenotype and the frequencies of CYP2C19 defective
      alleles, particularly CYP2C19*3 among these three Southeast Asian ethnics
      appeared to be lower than other Asian populations. Lower prevalence of CYP2C19 PM
      suggests that these ethnics may have different capacity to metabolize drugs that
      are substrates of CYP2C19. Certain drug dosage regiments should be considered
      differently for Asian populations.

PMID- 16946556
TI  - Peritoneal dialysis alters tolbutamide pharmacokinetics in rats with experimental
      acute renal failure.
AB  - The plasma concentration profile of the antidiabetic agent tolbutamide was
      investigated in glycerol-induced acute renal failure (ARF) rats receiving or not
      receiving peritoneal dialysis (PD) to assess the impact of performing dialysis on
      tolbutamide pharmacokinetics. It was revealed that the plasma concentration of
      tolbutamide was decreased by 23.4% by performing PD in ARF rats, while it was not
      changed by PD in normal rats. The decrease in the plasma concentration of
      tolbutamide was nearly proportional to the increase in its volume of
      distribution. To clarify the mechanisms responsible for the decreased tolbutamide
      concentration caused by PD, the plasma protein binding of tolbutamide was
      examined in normal and ARF rats. The plasma unbound fraction of tolbutamide was
      higher in ARF rats than in normal rats, and the dissociation constants were 3.5+/
      0.7 and 5.5+/-0.2 microg in normal and ARF rats, respectively. These results
      indicated that the unbound fraction of tolbutamide was increased in ARF rats
      because of its protein binding being suppressed. It is therefore likely that
      since a measurable amount of tolbutamide can distribute in peritoneal dialysate
      in ARF rats, but not in normal rats, the plasma concentration of tolbutamide was
      decreased by performing PD only in ARF rats. These findings suggest that diabetes
      medication with tolbutamide should be carefully performed in patients receiving
      dialysis treatment.

PMID- 16946554
TI  - Characterization of humanized liver from chimeric mice using coumarin as a human
      CYP2A6 and mouse CYP2A5 probe.
AB  - Coumarin 7-hydroxylation (COH), which is catalyzed almost solely by human CYP2A6
      and mouse CYP2A5, shows large differences in activity (humans>>mice) and
      inhibitor specificity between mice and humans. To differentiate human and mouse
      liver functions of chimeric mice (CM1, CM2 and CM3) prepared with hepatocytes
      from 3 donors, the microsomal COH activities were measured with and without
      benzaldehyde and undecanoic gamma-lactone as a specific inhibitor of human CYP2A6
      and mice CYP2A5, respectively. The replacement % to human hepatocytes designated
      as replacement index (RI) was calculated from human specific cytokeratin 8/18
      expression in the liver section. The COH activities correlated well with RIs in
      CM2 (R(2)=0.98) and CM3 (R(2)=0.94), except CM1 whose genotype of donor is
      CYP2A6*4/*4. However, the COH activities expressed as % of donor activities were
      not always coincident with RIs, and the inhibition pattern of CM2 and CM3 was
      human-type after RI exceeded approximately 50%. Subsequently, our attempts to use
      % of COH activities or inhibition patterns as an accurate functional replacement
      index were unsuccessful. Since the detection of human CYP2A6 protein in the liver
      and the steep increase of human albumin (hAlb) levels in the blood were begun
      from almost RI=50% similarly to the changes of inhibition pattern, RI=50% is the
      turning point for chimeric mice to have humanized liver function.

PMID- 16946557
TI  - Regulation of mRNA expression of MDR1, MRP1, MRP2 and MRP3 by prototypical
      microsomal enzyme inducers in primary cultures of human and rat hepatocytes.
AB  - The mRNA induction of various transporters by rifampicin (Rif), dexamethasone
      (Dex) and omeprazole (Ome) was investigated in primary cultures of cryopreserved
      human and rat hepatocytes. Analysis was performed by quantitative real-time RT
      PCR using primers and TaqMan probes. In primary cultures of human hepatocytes,
      mRNA levels of MDR and MRP1 were increased by about 1.5 fold and 1.3 fold,
      respectively, by exposure to Rif at 2 to 50 microM as compared with 0.1% DMSO
      treated controls. MRP2 mRNA levels in the same human hepatocytes were
      significantly increased by 1.2 to 1.8 fold by exposure to Rif at 50 microM as
      compared with controls. In primary cultures of rat hepatocytes, Mdr1a and Mdr1b
      mRNA levels were not increased or only slightly increased at 24 hr by exposure to
      any of the inducers at 2, 10 or 50 microM. Mrp2 mRNA levels in the same rat
      hepatocytes were significantly increased by 7 to 45 fold by exposure to Dex at 2
      microM as compared with controls. Based on the species differences observed in
      the present study, primary cultures of cryopreserved hepatocytes from both the
      human and rat should be useful in preclinical drug development for evaluating
      candidate drugs for transporter induction.

PMID- 16946558
TI  - Transporter-mediated intestinal absorption of fexofenadine in rats.
AB  - Both influx and efflux transporters are thought to be involved in the intestinal
      absorption of fexofenadine. The present study examined the influx transporter
      mediated intestinal absorption of fexofenadine in rats, focusing on the role of
      rat oatp3 (Oatp1a5). The intestinal permeability of fexofenadine was evaluated by
      means of the Ussing chamber method in the presence of a P-glycoprotein inhibitor
      to block efflux transport. The permeability of fexofenadine from the mucosal to
      the serosal side was higher than that from the serosal side to the mucosal side.
      Transport of fexofenadine was saturable, and was significantly decreased by an
      organic anion transporting polypeptide (oatp) inhibitor. Furthermore, uptake of
      fexofenadine by Xenopus oocytes expressing rat oatp3 was significantly greater
      than that by water-injected oocytes, and the affinity of oatp3 for fexofenadine
      (Km) was about 60 microM, which is comparable with the value obtained by the
      Ussing chamber method using rat intestinal tissues. These results indicate that
      oatp3 plays a role as an influx transporter in the intestinal absorption of
      fexofenadine in rats.

PMID- 16946559
TI  - Chenodeoxycholic acid-mediated activation of the farnesoid X receptor negatively
      regulates hydroxysteroid sulfotransferase.
AB  - Hydroxysteroid sulfotransferase catalyzing bile acid sulfation plays an essential
      role in protection against lithocholic acid (LCA)-induced liver toxicity. Hepatic
      levels of Sult2a is up to 8-fold higher in farnesoid X receptor-null mice than in
      the wild-type mice. Thus, the influence of FXR ligand (chenodeoxycholic acid
      (CDCA) and LCA) feeding on hepatic Sult2a expression was examined in FXR-null and
      wild-type mice. Hepatic Sult2a protein content was elevated in FXR-null and wild
      type mice fed a LCA (1% and 0.5%) diet. Treatment with 0.5% CDCA diet decreased
      hepatic Sult2a to 20% of the control in wild-type mice, but increased the content
      in FXR-null mice. Liver Sult2a1 (St2a4) mRNA levels were reduced to 26% in wild
      type mice after feeding of a CDCA diet, while no decrease was observed on Sult2a1
      mRNA levels in FXR-null mice after CDCA feeding. A significant inverse
      relationship (r(2)=0.523) was found between hepatic Sult2a protein content and
      small heterodimer partner (SHP) mRNA level. PCN-mediated increase in Sult2a
      protein levels were attenuated by CDCA feeding in wild-type mice, but not in FXR
      null mice. Human SULT2A1 protein and mRNA levels were decreased in HepG2 cells
      treated with the FXR agonists, CDCA or GW4064 in dose-dependent manners, although
      SHP mRNA levels were increased. These results suggest that SULT2A is negatively
      regulated through CDCA-mediated FXR activation in mice and humans.

PMID- 16946560
TI  - Population pharmacokinetic analysis of micafungin in Japanese patients with
      fungal infections.
AB  - The object of this analysis was to develop a population pharmacokinetic model of
      micafungin, a new anti-fungal agent of the echinocandin class, to optimize dosing
      in Japanese patients with fungal infections. Population pharmacokinetics
      parameters were determined using NONMEM based on pharmacokinetic data from 198
      subjects in seven clinical studies, comprising four phase I, two phase II and one
      pediatric phase III study. The healthy subjects received intravenous infusion of
      2.5-150 mg micafungin. Adult and pediatric patients, age range of 8 month to 15
      yeras old, were received 25-150 mg and 1-6 mg/kg daily, respectively. A total of
      1825 micafungin plasma samples were available for this analysis. Two-compartment
      pharmacokinetic model was adopted. The clearance of micafungin was influenced by
      body weight in children and platelet counts (PLT). However the PLT accounted for
      less than 20% of the variation of micafungin clearance in Japanese subjects. In
      conclusions, body weight is the primary covariate factor in pediatric patients.
      The dose adjustment by body weight would be required only pediatric patients for
      the micafungin therapy in Japanese patients with fungal infection.

PMID- 16946561
TI  - Three novel single nucleotide polymorphisms of the human thiopurine S
      methyltransferase gene in Japanese individuals.
AB  - In this study, the entire coding sequence and the exon-intron junctions of the
      thiopurine S-methyltransferase (TPMT) gene from 200 Japanese individuals were
      screened for mutation. Three novel single nucleotide polymorphisms (SNPs) were
      identified-106G>A in exon 3 (Gly36Ser, *20 allele), 967A>G in 3'-untranslated
      region, and -87C>T in intron 8. The allele frequencies were 0.003 for 106G>A,
      0.003 for 967A>G, and 0.010 for IVS8 -87C>T. In addition, the three known SNPs,
      474T>C (Ile158Ile), 719A>G (Tyr240Cys, *3C allele), and IVS4 +35C>T were detected
      at frequencies of 0.299, 0.010, and 0.421, respectively.

PMID- 16946562
TI  - Novel genetic variations and haplotypes of hepatocyte nuclear factor 4alpha
      (HNF4A) found in Japanese type II diabetic patients.
AB  - Thirty-nine single nucleotide variations, including 16 novel ones, were found in
      the 5' promoter region, all of the exons and their surrounding introns of HNF4A
      in 74 Japanese type II diabetic patients. The following novel variations were
      identified (based on the amino acid numbering of splicing variant 2): -208G>C in
      the 5' promoter region; 1154C>T (A385V) and 1193T>C (M398T) in the coding exons;
      1580G>A, 1852G>T, 2180C>T, 2190G>A, and 2362_2380delAAGAATGGTGTGGGAGAGG in the 3'
      untranslated region, and IVS1+231G>A, IVS2-83C>T, IVS3+50C>T, IVS3-54delC,
      IVS5+173_176delTTAG, IVS5-181_-180delAT, IVS8-106A>G, and IVS9-151A>C in the
      introns. The allele frequencies were 0.311 for 2362_2380delAAGAATGGTGTGGGAGAGG,
      0.054 for 1580G>A, 0.047 for 1852G>T, 0.020 for IVS1+231G>A, 0.014 for IVS9
      151A>C, and 0.007 for the other 11 variations. In addition, one known
      nonsynonymous single nucleotide polymorphism, 416C>T (T139I), was detected at a
      0.007 frequency. Based on the linkage disequilibrium profiles, the region
      analyzed was divided into three blocks. Haplotype analysis determined/inferred
      10, 16, and 12 haplotypes for block 1, 2, and 3, respectively. Our results on
      HNF4A variations and haplotypes would be useful for pharmacogenetic studies in
      Japanese.

PMID- 16946563
TI  - Correlation of dysmetabolic risk factors with different anthropometric
      measurements.

PMID- 16946564
TI  - Increased red blood cells in patients with metabolic syndrome.

PMID- 16946565
TI  - A case of polyglandular autoimmune syndrome type III complicated with autoimmune
      hepatitis.
AB  - A 58-year-old woman complaining of finger tremor was referred to our hospital.
      The diagnosis of Graves' disease was made based on increased free
      triiodothyronine (18.88 pg/ml) and free thyroxine (7.47 ng/dl), low TSH (<0.005
      microIU/ml) and increased TSH receptor binding antibody activity (70.9%). Serum
      level of AST (62 U/l) and ALT (93 U/l) were increased and liver biopsy revealed
      linkage of adjacent portal areas by lymphoplasmacytic infiltrates and fibrosis
      with piecemeal necrosis. Although antinuclear antibody was negative, these
      findings indicated that she had autoimmune hepatitis (AIH) according to the
      criteria of the International Autoimmune Hepatitis Scoring System. Slowly
      progressive type 1 diabetes mellitus (DM) was confirmed by a diabetic response
      pattern due to 75 g-oral glucose tolerance test, and seropositivity towards anti
      glutamic acid decarboxylase (725 U/ml) and islet cell (80 JDF Units) antibodies.
      This case exhibited an extremely rare combination of three different autoimmune
      diseases, including Graves' disease, slowly progressive type 1 DM and AIH, and
      had no known sensitive human leukocyte antigen (HLA) typing or haplotype for
      these disorders. Although it is common for patients with Graves' disease to
      exhibit abnormal liver function, it is important to make an accurate diagnosis of
      AIH because of this life-threatening disorder.

PMID- 16946566
TI  - Low-dose growth hormone treatment (0.175 mg/kg/week) for short stature in
      patients with Turner Syndrome: data from KIGS Japan.
AB  - Turner syndrome is a common sex chromosome anomaly. Human growth hormone (hGH) is
      effective for treating short stature, which is a major characteristic of the
      disease. In this report, we analyzed the results of low-dose GH treatment for
      short stature in 212 Turner syndrome patients with growth hormone deficiency.
      These patients were enrolled in KIGS Japan. After 5 years of treatment, change in
      height was more than the mean growth curve in many patients, and the standard
      deviation (SD) for stature improved by +1.22 SDS. As the treatment progressed,
      the weight-for-height index (WHI) decreased in patients aged 8.1 years or older
      but not more than 14.8 years at the commencement of the treatment.

PMID- 16946567
TI  - Molecular detection of SYT-SSX fusion gene transcripts currently represents the
      most specific and sensitive tool for diagnosing intrathoracic synovial sarcoma.

PMID- 16946568
TI  - Are there any other organs in which autoimmune pancreatitis-associated lesions
      remain to be identified?

PMID- 16946569
TI  - Lower level of low-density lipoprotein cholesterol by statin prevents progression
      of coronary restenosis after successful stenting in acute myocardial infarction.
AB  - OBJECTIVE: It is unclear whether the reduction of coronary restenosis by statins
      is due to a decrease in low-density lipoprotein (LDL) cholesterol and/or
      pleiotropic effects. Therefore, we performed quantitative coronary angiography
      (QCA) and analyzed the lipid profile and changes in adhesion molecules and
      chemokines caused by statin in patients with acute myocardial infarction (AMI).
      METHODS: The subjects included AMI patients who had initial coronary angiograms
      and significant coronary stenosis and were implanted with a stent. After stent
      implantation, patients were treated either with (n = 36) or without (n = 14)
      statin. The primary end-point for this study was the absolute changes in the
      lipid profile, C-reactive protein (CRP), adhesion molecules, chemokines and
      stenosis measured by QCA between the post-stent and follow-up angiogram at 6
      months after stenting. RESULTS: Treatment with statin reduced % coronary diameter
      stenosis (DS) and was associated with a greater reduction in LDL cholesterol at 6
      months after stenting in patients with acute myocardial infarction (AMI), while
      there were no differences in adhesion molecules, chemokines, CC chemokine
      receptor or CXC chemokine receptor. Interestingly, changes in % DS between before
      and after statin treatment at 6 months (Delta%DS) were positively correlated with
      DeltaLDL cholesterol, and patients who had an LDL cholesterol level of less than
      80 mg/dl had a significantly lower Delta%DS. In addition, Delta%DS was
      significantly related only to the reduction in LDL cholesterol as assessed by a
      stepwise multivariable regression analysis. CONCLUSION: These results suggest
      that the lower level of LDL cholesterol is the most critical factor in preventing
      coronary restenosis.

PMID- 16946570
TI  - Relationship between sleep-disordered breathing and lifestyle-related illnesses
      in subjects who have undergone health-screening.
AB  - OBJECTIVE: Simplified sleep polysomnography was performed in 207 adult men to
      examine the relationship between the frequency of sleep-disordered breathing
      (SDB) and lifestyle-related illness. METHODS: Each subject was checked for SDB
      using a simplified sleep polysomnograph (Auto-Set Portable; Teijin Limited,
      Tokyo, Japan). Apnea and hypopnea were detected with a nasal cannula type airflow
      sensor. Hypoxemia was checked with a percutaneous oxygen saturation (SpO2)
      monitor. We analyzed the relationships between SDB and body mass index (BMI) and
      hypertension, hyperlipidemia, liver dysfunction, fatty liver, and abnormal
      glucose metabolism. RESULTS: Fifty-nine subjects (29%) showed SDB with apnea
      hypopnea index (AHI) over 15 times/h. The frequency of obesity (BMI > or = 25),
      hypertension, hypercholesterolemia, fasting blood glucose level, and HbA1c were
      significantly higher in patients with SDB than in normal individuals (AHI < 5
      times/h). The frequencies of hypertension, hyperlipidemia, and abnormal glucose
      metabolism were compared between the obesity-free normal AHI group and the SDB
      group, and only that of hypertension was significantly different between the two
      groups. CONCLUSIONS: The present study revealed a high frequency of SDB among
      Japanese individuals. The results also suggest that as SDB becomes severe, it
      becomes more closely linked to the onset of lifestyle-related illnesses, such as
      hypertension, hypercholesterolemia and abnormal glucose metabolism.

PMID- 16946571
TI  - IgG4-associated prostatitis complicating autoimmune pancreatitis.
AB  - A 65-year-old man underwent transurethral resection of the prostate on a
      diagnosis of benign prostatic hypertrophy. Almost simultaneously, a diagnostic
      resection of minor salivary glands was performed. After the resections he
      suffered from obstructive jaundice. Laboratory examinations revealed an increase
      in eosinophils and an elevation of serum IgG4. Pancreaticoduodenectomy was
      performed because of the possibility of pancreatic cancer. The prostate, salivary
      glands and pancreas showed common histological characteristics, namely,
      infiltration of lymphocytes and plasma cells accompanying dense fibrosis. Most of
      the infiltrating plasma cells showed strong immunoreactivity to IgG4. This is the
      first case with IgG4-associated prostatitis complicating autoimmune pancreatitis.

PMID- 16946572
TI  - Vascular Behcet's disease with coronary artery aneurysm.
AB  - A 33-year-old man with a 4-year history of Behcet's disease was hospitalized with
      acute myocardial infarction. Percutaneous coronary intervention (PCI) treated 99%
      stenosis of the right coronary artery but follow-up coronary arteriography
      clearly revealed a coronary artery aneurysm (CAA) at the lesion proximal to the
      PCI site and intravascular ultrasound confirmed that it was a true aneurysm. We
      speculated that Behcet's disease might be involved in coronary lesion, especially
      in CAA formation. We decided to increase the dose of prednisolone and to add
      warfarin. The size of the CAA was not altered after 6 months.

PMID- 16946573
TI  - Sinus of Valsalva thrombosis causing renal infarction.
AB  - A 72-year-old man was admitted to our hospital with a renal infarction. On
      admission, computed tomography (CT) of the abdomen revealed total occlusion of
      the right renal artery, which was found to be recanalized with residual thrombus
      7 days later. Transesophageal echocardiography and chest CT demonstrated crescent
      shaped thrombus in the non-coronary sinus of Valsalva without evidence of
      aneurysm. After coumadin treatment the patient did not experience recurrent
      episodes of systemic embolization. Five months after the initiation of
      anticoagulation, transesophageal echocardiography and chest CT demonstrated
      disappearance of the thrombus. This is a rare case of renal infarction caused by
      a thrombus in the non-coronary sinus of Valsalva without aneurysm.

PMID- 16946574
TI  - Pulmonary nontuberculous mycobacterial infection caused by Mycobacterium szulgai
      in a young healthy woman.
AB  - A 20-year-old woman with no history of pulmonary disease had no symptom and her
      chest CT scans demonstrated adhesive small multiple nodules in the bronchial lung
      biopsy specimen showed epithelioid cell granuloma containing Langhans giant
      cells, therefore she was diagnosed as pulmonary mycobacteriosis caused by M.
      szulgai. This is the youngest case of this rare condition occurring in a healthy
      subject without underlying pulmonary diseases.

PMID- 16946575
TI  - Silico-asbestosis that responded to steroid therapy.
AB  - A 73-year-old man with silico-asbestosis responded to steroid therapy. Chest CT
      scans showed diffuse micronodular opacities and ground glass opacities
      bilaterally throughout the entire lung fields, as well as progressive massive
      fibrosis in the bilateral upper lung fields. Diagnostic thoracoscopic biopsy
      revealed mixed dust pneumoconiosis with silicotic nodules, as well as fibrosis
      similar to that of Usual Interstitial Pneumonia (UIP) with many fibroblastic foci
      and alveolitis. Many asbestos bodies were also detected by iron staining.

PMID- 16946576
TI  - Angiosarcoma with sacral origin metastasizing to the lung.
AB  - A 73-year-old man with fever, lumbago and hemosputum showed ground-glass opacity
      around multiple lung nodules on chest computed tomography. Examination of the man
      revealed anemia. Specimens obtained by video-assisted thoracic surgery revealed
      angiosarcoma, but the primary site of angiosarcoma could not be detected before
      autopsy. Angiosarcoma is a rare malignant neoplasm with rapid proliferation and
      they can arise at any region of the body. It can originate in the skin, soft
      tissue, liver or heart. Their multicentric and local recurrence easily leads us
      to misdiagnosis, and we have struggled to reach diagnosis and its origin.
      Angiosarcoma should be included in the different diagnosis of diffuse pulmonary
      hemorrhage with multiple lung nodules.

PMID- 16946577
TI  - Salazosulfapyridine-induced encephalopathy with symmetrical lesions in the basal
      ganglia and thalami.

PMID- 16946578
TI  - Pneumopericardium: a rare triggering factor for Takotsubo cardiomyopathy.

PMID- 16946579
TI  - Ruptured pheochromocytoma presenting with acute abdomen and pulmonary edema.

PMID- 16946580
TI  - Hummingbird and squint eyes in progressive supranuclear palsy.

PMID- 16946581
TI  - Adult-onset Still's disease: evaluation by gallium-67 citrate scintigraphy.

PMID- 16946582
TI  - Changes in circulating and testicular levels of inhibin A and B during postnatal
      development in bulls.
AB  - We investigated testicular and circulating levels of dimeric inhibins in Holstein
      bulls from the infantile to postpubertal periods (5 to 50 weeks of age) and
      examined the relationship between the profiles of circulating dimeric inhibins
      and FSH. Concentrations of total inhibin and inhibin B in the testis were highest
      at 4 to 5 weeks of age but decreased gradually as the bulls aged. Testicular
      inhibin A levels showed a gradual decline to a nadir at 15 to 26 weeks of age,
      but by 39 weeks, they were high again. The contents of total inhibin, inhibin A,
      and inhibin B per testis generally increased with age. Fractionation of
      testicular homogenates obtained from 15-week-old bulls by a combination of
      immunoaffinity chromatography and SDS-PAGE confirmed the presence of two major
      molecular weight forms (32 and 45 kDa) of dimeric inhibins in the testes.
      Circulating levels of total inhibin and inhibin A showed a significant increase
      in bulls at around 10 to 14 weeks of age compared to the levels between 5 and 7
      weeks of age but decreased thereafter. However, immunoreactivity for inhibin B
      was not detected in the peripheral circulation, probably because of low
      sensitivity of the inhibin B assays. The concentrations of plasma FSH were high
      at 5 weeks of age but declined to lower levels between 11 and 40 weeks, and then
      increased from 41 weeks onward. There was no significant correlation between the
      plasma levels of FSH and inhibin A or total inhibin. The results clearly indicate
      that the bull testis produces inhibin A and B and secretes at least inhibin A
      into the circulation during postnatal development. However, the profile of
      circulating FSH in bulls shows no reciprocal relationship with the inhibin A or
      total inhibin profile during the postnatal period.

PMID- 16946583
TI  - [UVB-induced skin damage and the protection/treatment--effects of a novel,
      hydrophilic gamma-tocopherol derivative].
AB  - Ultraviolet radiation is the major environmental cause of skin damage. Although
      only 0.5% of ultraviolet B (UVB) radiation reaches the earth, it is the main
      cause of sunburn and inflammation and the most carcinogenic constituent of
      sunlight. We investigated whether the topical application of a novel, water
      soluble gamma-tocopherol (gamma-Toc) derivative, gamma-tocopherol-N,N
      dimethylglycinate hydrochloride (gamma-TDMG), could protect against UV-induced
      skin damage. Topical pre- or postapplication of gamma-TDMG solution significantly
      prevented sunburn cell formation, lipid peroxidation, and edema/inflammation that
      were induced by exposure to a single dose of UV irradiation. Cyclooxygenase-2
      (COX-2)-catalyzed synthesis of prostaglandin E(2) (PGE(2)) levels seen after UV
      exposure were significantly suppressed by pre- or posttreatment with gamma-TDMG.
      The increase in COX-2 activity was significantly inhibited by gamma-TDMG,
      suggesting that the reduction in PGE(2) concentration was due to the direct
      inhibition of COX-2 activity by gamma-TDMG. The derivative strongly inhibited
      inducible nitric oxide synthase mRNA expression and nitric oxide production. With
      the application of gamma-TDMG, the pigmentation in melanocytes was lightened and
      the increase melanin concentration was suppressed. Gamma-TDMG is converted to
      gamma-Toc in the skin and has higher bioavailability than gamma-Toc itself. These
      results suggest that gamma-TDMG-derived gamma-Toc acts as an antioxidant,
      antiinflammatory and antipigmentation agent. Our data further suggest that the
      topical application of gamma-TDMG may be efficacious in preventing and reducing
      UV-induced skin damage in humans.

PMID- 16946584
TI  - [Mechanisms of hypertension in the central nervous system].
AB  - This article reviews studies by the author on central mechanisms of hypertension.
      Spontaneously hypertensive rats (SHR) have been developed as a rat model of
      genetic hypertension, and central acetylcholine has been implicated in
      hypertension in SHR. The rostral ventrolateral medulla (RVL), a major source of
      efferent sympathetic activity, has cholinergic pressor systems. The release of
      acetylcholine is enhanced in the RVL of SHR, leading to hypertension. The
      alteration of the RVL cholinergic system in SHR results from enhanced angiotensin
      systems in the anterior hypothalamic area (AHA). Angiotensin II-sensitive neurons
      are present in the AHA and they are tonically activated by endogenous
      angiotensins. The basal activity of AHA angiotensin II-sensitive neurons is
      enhanced in SHR, mainly due to enhanced sensitivity of AHA neurons to angiotensin
      II. The AHA angiotensin system is also responsible for hypertension induced by
      emotional stress and central Na(+) increases. These findings suggest that the AHA
      angiotensin system may play a critical role in the development of hypertension.

PMID- 16946585
TI  - [Claudin as a novel target for drug delivery system].
AB  - Recent remarkable progress in genomic novel drug discovery enables us to prepare
      drug candidates with tremendous diversity in a high-throughput-manner. In
      clinical use of these candidates, they should be effectively delivered to a
      target-tissue in body. But delivery systems suitable for the high-throughput
      discovery of drugs have never been established. Tight junctions (TJs) play a
      pivotal role in compartmentation of each tissues and maintenance of their intra
      circumstances. Claudin, a membrane protein with four trans-membrane domains, have
      recently found to be responsible for the barrier-function of TJs. Claudin is
      constituted of 24 family members, and expression profiles and barrier-function of
      claudin differ interestingly among the family members. These findings indicate
      that a modulator of the unique barrier-function of claudin may be used for drug
      delivery. In this respect, we have investigated whether a claudin is a target for
      drug delivery. A claudin modulator (C-terminal fragment of Clostridium
      perfringens enterotoxin, C-CPE) had 400-fold jejunal absorption-enhancing
      activity to a clinically used absorption-enhancer, and interaction between C-CPE
      and claudin was essential for the enhancing activity. We have already prepared a
      screening system for claudin-targeting molecule. Now we are performing functional
      domain mapping of C-CPE, and we will attempt to prepare a various type of claudin
      modulator in a future. In the current review, I introduce our recent works on
      development of a novel strategy for drug delivery system using claudin modulator,
      and I discuss also possibility of claudin modulator in drug delivery system.

PMID- 16946586
TI  - [Pharmacokinetic study of cancer chemotherapy].
AB  - We reported that the rate of conversion of lactone to carboxylate forms of
      irinotecan (CPT-11) and its metabolites plays a major role in the biliary
      excretion of these compounds. Sulfobromophthalein partially inhibited the
      secretion of SN-38-glucronide into the gastrointestinal lumen, whereas little
      change was seen in that of active metabolite SN-38. Co-administration of
      sulphobromophthalein with CPT-11 might lower the late-onset gastrointestinal
      toxicity observed during treatment with CPT-11 without lowering anticancer
      activity. In the ileum, the level of transport in the direction form the serosal
      layer to mucosal layer was significantly greater than that in the direction form
      the mucosal layer to serosal layer, whereas a significant difference was not
      observed in the jejunum. This secretory transport required metabolic energy was
      diminished by sulfobromophthalein. A specific transport system plays a major role
      in the secretion of SN-38 and that this secretory transport system predominantly
      exists in the ileum. Uptake of SN-38 was significantly reduced at 4 degrees C.
      Baicalin inhibited the uptake of SN-38. A specific transport system mediates the
      uptake of SN-38 across the apical membrane in Caco-2 cells. Inhibition of this
      transporter would be a useful means for reducing late-onset diarrhea.

PMID- 16946587
TI  - [Study on the highly efficient synthesis and pharmaceutical evaluation of PET
      radiopharmaceuticals for the clinical application].
AB  - Positron Emission Tomography (PET) is an advanced non-invasive technology used in
      the field of nuclear medicine for clinical diagnosis using radiotracers labeled
      with short-lived positron emitting radionuclides such as (11)C (half-life: 20.4
      min), (13)N, (15)O and (18)F. The present study describes an efficient rapid
      synthesis method for [(11)C]Phosgene ([(11)C]COCl(2)) which is an important
      potential precursor for preparation of PET radiopharmaceuticals. Catalytic
      oxidation of [(11)C]CCl(4) using Fe(2)O(3) powder mixed with Fe granules as an
      oxidizing agent was newly accomplished with a development of fully automated
      synthetic apparatus. Utilization of produced [(11)C]COCl(2) provided a
      substantial synthesis of [2-(11)C]thymine as a key intermediate for preparation
      of [2-(11)C]thymidine, a PET tracer to evaluate cellular proliferation. Direct
      ring closure reaction of the alkali metal salt of beta-(N-benzoyl
      amino)methacrylamide with [(11)C]COCl(2) readily proceeded under mild conditions
      to afford [2-(11)C]thymine in fair yield reproducibly. By way of further
      application, a useful PET ligand for beta-adrenoreceptors, S-(-)-[(11)C]CGP-12177
      (CGP) was synthesized in markedly high yield with high specific activity and
      radiochemical purity. CGP for intravenous injection was prepared in 25 min after
      EOB with a yield of 1.5+/-0.2 GBq. These results of quality control tests
      demonstrated that CGP preparation is suitable for routine clinical use. Thus, CGP
      PET study has been newly added to clinical PET for cardiac functional
      investigation in Hokkaido University Hospital.

PMID- 16946588
TI  - [Development of anti-dementia drugs related to neurotrophic factors].
AB  - Neurotrophic factor-like substances and inducers of neurotrophic factor
      biosynthesis have enormous therapeutic potential for serious neuronal diseases
      such as Alzheimer's disease. Here, we discuss about the pharmacological effects
      of scabronines and beta-eudesmol as promising candidates of leading compounds
      against the dementia. In addition, we discuss about the signaling pathway of
      nerve growth factor and cyclic AMP in order to seek the signaling molecules as
      targets of drug development.

PMID- 16946589
TI  - [Development of environmentally benign oxidations using hypervalent iodine (III)
      reagents].
AB  - We have synthesized a novel, nonpolymer-supported recyclable hypervalent iodine
      (III) reagent, 1,3,5,7-tetrakis[4-(diacetoxyiodo)phenyl]adamantane 3a and its
      derivatives 3b, c and utilized them in environmentally benign oxidations. The new
      reagents 3a-c mediate a wide range of oxidative transformations with efficiencies
      similar to those of conventional reagents, phenyliodine (III) diacetate (PIDA),
      pheyliodine (III) bis (trifluoroacetate) (PIFA), and (hydroxyl(tosyloxy)iodo).
      benzene (HTIB), and have higher reactivity compared with polymer-supported
      recyclable reagents such as poly(diacetoxyiodo)styrene (PDAIS) and
      poly{bis(trifluoroacetoxy)iodo}styrene (PBTIS). In all cases, tetraiodide 4 was
      recovered nearly quantitatively in a pure form after simple workup, i.e.,
      filtration. Reoxidation of 4 to 3a with m-chloroperbenzoic acid also proceeded
      quantitatively, without loss of oxidative activity. Recyclable 3a-c are used in
      various organic solvents as well as water, and thus mild and clean oxidation of
      alcohols in water has been achieved using 3a. A facile synthesis of aldehydes
      from primary alcohols has also been demonstrated using a dual recycling strategy,
      with 3a and recyclable 2,2,6,6-tetramethyl-1-piperidinyloxy free radical (TEMPO).

PMID- 16946590
TI  - [Clinicopharmacological study of gastrointestinal drugs from the viewpoint of
      postmarketing development].
AB  - Pharmaceutical development starts with the discovery of a new compound. Drugs
      become commercially available after non-clinical and clinical studies, but
      processes that take place after marketing are also important for pharmaceutical
      development. In recent years, use of the phrase "Ikuyaku" meaning postmarketing
      development has become more common. Sometimes, the proper usage, indications and
      harmful effects of a drug are discovered only after it becomes commercially
      available and is administered to many patients. Hence, pharmacists need to
      actively perform postmarketing studies to reveal the true nature of drugs. In the
      present clinicopharmacological study, we investigated the effects of histamine
      H(2) receptor antagonists (H(2)-RAs) on the plasma concentrations of
      gastrointestinal peptides from the viewpoint of postmarketing development. First
      we established an enzyme immunoassay for secretin, which is involved in
      gastrointestinal motility. Then we used this and existing peptide assays to
      investigate the above-mentioned issues. Ranitidine and nizatidine increased the
      plasma concentration of motilin. It is believed that the plasma concentration of
      Ach is elevated by ranitidine and nizatidine, which possesses an anti-AchE
      activity, and that the increased the plasma concentration of Ach facilitated
      release of motilin, elevating the plasma concentration of motilin. When compared
      to the placebo, lafutidine significantly increased the plasma concentration of
      CGRP (calcitonin gene-related peptide) and substance P. Furthermore, released
      CGRP stimulated CGRP1 receptors to facilitate secretion of somatostatin.
      Therefore, lafutidine appears to protect the gastric mucosa and regulate
      gastrointestinal motility. The same results were obtained with ranitidine and
      nizatidine. While H(2)-RAs have a common function in suppressing the secretion of
      gastric acid, they do not exhibit the same effects on factors related to
      recurrence of peptic ulcer, such as gastrointestinal motility and blood flow in
      the gastrointestinal mucosa. Hence, measuring the plasma concentration of
      gastrointestinal peptides can be used to estimate the effects of drugs on
      gastrointestinal motility. From the viewpoint of postmarketing development, we
      are in the process of establishing indicators for the proper usage of
      pharmaceutical drugs. Pharmacists need to closely follow and monitor adverse
      reactions. In order to further improve monitoring of drug therapy, it will be
      necessary to assess not only the blood concentrations of drugs, but also
      biological reactions to the drugs. Since the levels of peptides reflect the
      clinical efficacy of gastrointestinal drugs, measuring peptide levels appears to
      be useful for selecting appropriate drugs.

PMID- 16946591
TI  - [Synthesis and optical properties of the helical oligonaphthalenes].
AB  - We have developed an efficient synthesis method for optically active
      oligonaphthalenes (from 2 mer to 16 mer), which are connected at their 1,4
      positions, under oxidative homo coupling with a stoichiometric amount of CuCl(2)
      and amines. The absolute configuration of the newly formed axis bond was
      determined based on the CD spectra of oligonaphthalenes with 1) two pyrene rings
      on the central naphthalenes or 2) two tetraphenylporphyrins (TPP) on the top and
      bottom naphthalenes. The fluorescence quantum yields increased as the number of
      naphthalene units increased in methoxy derivatives 10-12, and the intramolecular
      energy transfer quantum yields of bispyrene derivatives 7-9 were around 20%
      regardless of the number of naphthalene units. Furthermore, the
      hexadecanaphthalene derivative 4b with two TPPs exhibited a clear exciton
      coupling over an interchromophore distance to ca. 66 A.

PMID- 16946592
TI  - Preparation of N-succinyl-chitosan and its physical-chemical properties as a
      novel excipient.
AB  - The aim of this work is to prepare N-succinyl-chitosan (Suc-Chi) and measure
      physical-chemical properties for Suc-Chi as excipients. Suc-Chi were prepared via
      ring-opening reactions with succinic anhydride in Dimethyl Sulfoxide system. The
      physical-chemical properties of Suc-Chi, such as the degree of substitution (DS),
      solubility, isoelectric point (pI), glass transition temperature (Tg), partition
      coefficient (P(app)) and zata potential were detected respectively in order to
      evaluate their possibility as drug carriers. We obtained Suc-Chi DAC-90 (DS=0.33)
      and the data of physical-chemical properties for the product. The knowledges of
      physical-chemical properties for Suc-Chi are valuable for basic or applied
      purposes in biomedical and pharmaceutical sciences stabilization.

PMID- 16946593
TI  - Antiamnesic effects of Desmodium gangeticum in mice.
AB  - Dementia is a mental disorder characterized by loss of intellectual ability
      sufficiently severe enough to interfere with one's occupational or social
      activities. Desmodium gangeticum commonly known as Salparni, is widely used in
      ayurveda for the treatment of neurological disorders. The present work was
      designed to assess the potential of aqueous extract of D. gangeticum (DG) as a
      nootropic agent in mice. DG (50, 100 and 200 mg/kg, p.o.) was administered for 7
      successive days to both young and older mice. Exteroceptive behavioral models
      such as elevated plus maze and passive avoidance paradigm were employed to
      evaluate learning and memory. Scopolamine (0.4 mg/kg, i.p.) induced amnesia and
      ageing induced amnesia were the interoceptive behavioral models. To delineate the
      mechanism by which DG exerts nootropic activity, the effect of DG on whole brain
      AChE activity was also assessed. Piracetam (200 mg/kg, i.p.) was used as a
      standard nootropic agent. Pretreatment with DG (50, 100 and 200 mg/kg p.o.) for
      seven successive days significantly improved learning and memory in mice and
      reversed the amnesia induced by both, scopolamine (0.4 mg/kg, i.p.) and natural
      ageing. DG also decreased whole brain acetyl cholinesterase activity. Hence, D.
      gangeticum appears to be a promising candidate for improving memory and it would
      be worthwhile to explore the potential of this plant in the management of
      dementia and Alzheimer disease.

PMID- 16946594
TI  - [Optimum preparation of levocarnitine chloride solution in the hospital
      pharmacy].
AB  - Levocarnitine chloride is used for the therapeutic purpose of levocarnitine
      deficiency. For infants, however, levocarnitine chloride tablets must be crushed
      to avoid difficulties associated with swallowing, and also to administer an
      appropriately low dosage. Since the tablet is extremely hygroscopic and sour, it
      is dissolved in water containing simple syrup after crushing. In this study we
      investigated the stability of the drug after dissolution to optimize its
      preparation for clinical use. It was shown to be stable for at least 90 days
      after preparation, and microbes did not grow in 1-10% (w/v) solutions (pH 2.0
      2.5) regardless of the presence or absence of simple syrup. Furthermore, the
      autoclaved levocarnitine chloride solution was as stable as the non-autoclaved
      one. In conclusion, the method employed in our hospital for the preparation of
      levocarnitine chloride for infants is appropriate and is recommended as a
      standard medicine supply method among different facilities.

PMID- 16946595
TI  - Determination of chlorogenic acid in rat plasma by high performance
      chromatography after peritoneal administration of compound Daqingye injection.
AB  - A simple and sensitive high performance liquid chromatographic method has been
      developed for the determination of chlorogenic acid (3-O-caffeoyl-D-quinic acid)
      in rat plasma and applied to its pharmacokinetic study in rats after peritoneal
      administration of compound Daqingye injection. Plasma samples are extracted with
      perchloric acid. HPLC analysis of the chlorogenic acid is performed on a C(18)
      reversed-phase column using methanol-water (80: 20, v/v, pH 2.8) as mobile phase
      with UV detector set at 327 nm. The standard curves are linear in the range of
      0.200-10.0 microg/ml (r=0.9982). The inter- and intra-day precision (relative
      standard deviation) was less than 9% and the accuracy (relative error) was less
      than 10%. The limit of quantitation was 0.200 microg/ml. The plasma concentration
      of chlorogenic acid shows a C(max) of 7.53+/-0.52 microg/ml at 13.33+/-4.00 min
      with a t(1/2) of 59.10+/-5.42 min.

PMID- 16946596
TI  - [Analysis of the chemical drugs among structural isomer].
AB  - Drugs that have a pharmacological effect similar to legal drugs such as narcotics
      and stimulants are available in the market and widely used. 5-methoxy-N,N-di-iso
      propyl-tryptamine (5MeO-DIPT) and alpha-methyl-tryptamine (AMT) were categorized
      as narcotics and were specified as legal drugs in April 2005, and also 2,5
      dimethoxy-4-n-propylthiophenethylamine (4C-T-7) and N-methyl-alpha-ethyl-3,4
      methylenedioxy-phenethylamine (MBDB) were categorized as narcotics and were
      specified as legal drugs in April 2006, in Japan. We are analyzing these chemical
      drugs by investigating the market research. It is recognized that during the
      analysis of chemical drugs, drugs that resemble a structural isomer of a target
      substance, such as 5MeO-DIPT and 5-methoxy-N,N-di-n-propyl-tryptamine (5MeO-DPT)
      or 4C-T-7 and 2,5-dimethoxy-4-iso-propylthiophenethylamine (4C-T-4), should be
      distinguished. The results of TLC, IR, GC-MS and HPLC analyses were compared.
      5MeO-DIPT and 5MeO-DPT could be distinguished by TLC and HPLC analyses, but not
      by IR and GC-MS analysis. The drugs 4-hydroxy-N-methyl-N-iso-propyl-tryptamine
      (4HO-MIPT) and 4-hydroxy-N,N-di-ethyl-tryptamine (4HO-DET) or could not be
      distinguished. Moreover, the isomers of 4-hydroxy-N-methyl-N-n-propyl-tryptamine
      (4HO-MPT) was not found to be present. Thus, we have demonstrated that the
      chemical drug could be distinguished from each other, and we have also shown that
      NMR data is essential for the analysis.

PMID- 16946597
TI  - Outcome of patients in relation to duration of new-onset atrial fibrillation
      following acute myocardial infarction.
AB  - AIM: The duration of new-onset atrial fibrillation (AF) following the acute
      myocardial infarction (AMI) was evaluated as well as its relation to in-hospital
      and 7-year mortality. METHODS AND RESULTS: A total of 320 consecutive patients
      with AF following AMI were examined and patients with AF <7 h (n = 141) were
      compared to those with AF > or =7 h in duration (n = 179). Receiver Operating
      Characteristic analysis was performed to identify the most useful AF duration cut
      off level for the prediction of poor outcome. Patients with longer AF duration
      were older and had more advanced heart failure than patients with short
      arrhythmia duration. Patients with longer AF duration had worse outcome,
      including higher in-hospital (22.3 vs. 12.8%) and 7-year (67.4 vs. 34.4%)
      mortality. After multivariate adjustment, longer AF duration remained an
      independent predictor of long-term mortality (relative risk = 2.04, 95%
      confidence interval = 1.39-2.99, p = 0.0002). CONCLUSION: New-onset AF > or =7 h
      in duration following the AMI independently predicts long-term mortality.

PMID- 16946598
TI  - Atrial fibrillation after percutaneous coronary intervention: predictive
      importance of clinical, angiographic features and P-wave dispersion.
AB  - Atrial fibrillation (AF) may occur during or after percutaneous coronary
      interventions (PCI). The purpose of the study was to determine the clinical,
      angiographic and electrophysiological predictors of AF after PCI. 225 patients
      undergoing PCI (mean age of 65 +/- 11 years) who had sinus rhythm (SR) before
      balloon inflation were taken to study. Of these 22 developed AF in
      catheterization laboratory after balloon inflation or in 24 h following PCI (AF
      group), 203 did not (SR group). The patients in AF group were older (67 +/- 9 vs.
      63 +/- 8 years, p < 0.05) and their ventricular ejection fraction was lower than
      SR group (56 +/- 5 vs. 45 +/- 7%, p < 0.05). The P-wave dispersion was
      significantly higher in AF group than SR group (53 +/- 8 vs. 29 +/- 10 ms, p <
      0.001). For the patients with ST elevation myocardial infarction, the time from
      the onset of symptoms to balloon inflation was 3.7 +/- 1.7 h in SR group. It was
      longer in AF group (4.1 +/- 1.8 h, p < 0.05). TIMI perfusion grades 2 and 3 were
      achieved in 23 of 27 patients in SR group, and 5 of 8 patients in AF group.
      Multivessel disease was documented in 93 of the patients in SR group, and 12 in
      AF group. Clinical reperfusion was thought to be established in 20 in SR group,
      and 4 in AF group. In conclusion, our results show the importance of clinical
      factors, angiographic results and P-wave analysis in prediction of AF following
      PCI.

PMID- 16946599
TI  - Anomalous origin of the entire coronary system with separate ostia within the
      right sinus of valsalva: a rare congenital anomaly and a review of the
      literature.
AB  - Congenital coronary artery malformations occur infrequently in the general
      population. In this report, we describe a rare case of anomalous origin of all
      three coronary arteries from separate ostia within the right coronary sinus.

PMID- 16946600
TI  - A case of pulmonary alveolar microlithiasis with cardiac constriction secondary
      to severe adjacent pleural involvement.
AB  - Pulmonary alveolar microlithiasis (PAM) is a rare disorder of uncertain etiology
      and pathogenesis that is characterized by tiny calcium phosphate depositions in
      lung alveoli. Ectopic organ involvement has been reported infrequently. We hereby
      present a patient with PAM complicated by severe pleural calcification that has
      caused a constrictive cardiac physiology, a heretofore unknown
      occurrence/association. Based on our observations in this particular case, we
      suggest that a non-invasive echocardiographic examination may be well worth in
      the investigation of PAM patients in whom symptom onset at an early age has
      occurred, particularly if severe pleural calcification adjacent to the heart is
      present.

PMID- 16946601
TI  - Are elderly patients with suspected HF misdiagnosed? A primary health care center
      study.
AB  - BACKGROUND: Few studies are published on heart failure patients in primary health
      care, in elderly in advanced age. OBJECTIVE: The purpose of this study was to
      examine the accuracy of the diagnosis of heart failure in all men and women with
      focus on age and gender. METHODS: The patients were recruited from one selected
      primary health care in the city of Skelleftea, Sweden. The general practitioners
      included all patients who had symptoms and signs indicating heart failure. The
      patients were then referred for an echocardiographic examination and a final
      cardiology consultation. RESULTS: The general practitioners identified 121 women
      and 49 men with suspected heart failure of whom 39% (51 women and 16 men) were
      above 80 years. Women were significantly older than men (mean age 78 and 75
      years, respectively, p = 0.03). The main symptom was dyspnoea (80%). Confirmed
      heart failure was verified in 45% of the patients and was significantly more
      common in men than women (p = 0.02). Of all men and women above 80 years, 75% and
      22%, respectively (p = 0.01) had a verified systolic heart failure, while there
      were no significant gender differences in patients younger than 80. In a
      multivariate regression analysis taking gender, age, smoking, atrial
      fibrillation, hypertension, angina, myocardial infarction and diabetes into
      account, myocardial infarction (OR = 4.3, CL = 1.8-10.6) hypertension (OR = 3.4,
      CI = 1.6-6.9) atrial fibrillation (OR = 2.8, CL = 1.0-7.9) remained significantly
      predictive of a confirmed diagnosis of heart failure. CONCLUSION: This study
      showed the difficulty of diagnosing heart failure accurately based only on
      clinical symptoms, especially in women above 80 years.

PMID- 16946602
TI  - Statistical aspects of design and analysis of clinical trials for the prevention
      of caries.
AB  - This paper considers the methods used in design and analysis of recent clinical
      trials of topical fluoride interventions designed to prevent the development of
      dental caries in children, with particular consideration given to issues related
      to cluster-randomized trials. Studies which met the inclusion criteria were
      recent clinical trials of topical fluoride interventions published since 1990,
      conducted in children under 16 years of age, with caries as the outcome variable.
      Papers not published in English were translated. Information was extracted from
      the published trial reports on the units of randomization and analysis. The
      papers were also studied to assess if reporting allowed the assessment of
      potential consent bias in cluster-randomized trials and the reproduction of
      sample size calculations. Fifteen trials published since 1990 were included, of
      which five were cluster randomized. Only 1 of the 5 accounted for the clustering
      in the analysis. For the other four trials, it was possible to calculate that
      values from 0.002 (for DMFS) and 0.08 (for being caries free) for the
      intracluster correlation coefficient within schools could result in statistically
      non-significant findings. 3 of the 5 cluster-randomized trials did not report the
      consenting procedure in enough detail to judge whether consent bias could be
      present. Only 1 of the total 15 trials reported a sample size calculation. In
      summary, researchers should be aware of the importance of correctly analyzing
      cluster-randomized data and thorough reporting of clinical trials according to
      the CONSORT guidelines.

PMID- 16946603
TI  - Are mutans streptococci detected in preschool children a reliable predictive
      factor for dental caries risk? A systematic review.
AB  - Research suggests that mutans streptococci play an important role in cariogenesis
      in children but the usefulness of bacterial testing in risk assessment is
      unknown. Our objective was to summarize the literature assessing the association
      of mutans streptococci and dental caries in preschool children, (Pre)Medline
      (1966-2003), Embase (1980-2003), the Cochrane Register of Controlled Trials
      (2003, issue 3), and reference lists of included studies were searched. All
      abstracts found by the electronic searches (n = 981) were independently
      scrutinized by 2 reviewers. Minimal requirements for inclusion were assessment of
      preschool children without caries at baseline, reporting of mutans streptococci
      present in saliva or plaque at baseline and assessment of caries presence after a
      minimum of 6 months of follow-up. Participants' details, test methods,
      methodological characteristics and findings were extracted by one reviewer and
      cross-checked by another. Homogeneity was tested using chi2 tests. Results of
      plaque and saliva testing were pooled separately using a fixed effects model.
      Methodological quality of reports was low. Out of 9 studies included, data from 3
      reports on plaque test assessment alone (n = 300) and from 4 reports on saliva
      test assessment alone (n = 451) were available for pooled analysis. The pooled
      risk ratio (95% CI) was 3.85 (2.48-5.96) in studies using plaque tests and 2.11
      (1.47-3.02) in those using saliva testing. Presence of mutans streptococci, both
      in plaque or saliva of young caries-free children, appears to be associated with
      a considerable increase in caries risk. Lack of adjustment for potential
      confounders in the original studies, however, limits the extent to which
      interpretations for practice can be made.

PMID- 16946604
TI  - Effectiveness of sealants in adolescents with high and low caries experience.
AB  - The aim of this 3-year longitudinal study was to analyze caries increment and the
      caries-preventive effect of sealants in adolescents in the setting of the German
      national health system. 434 pupils (193 male, 241 female) took part in compulsory
      school examinations at age 12 (mean 12.3 +/- 0.4 years) and 15 (mean 15.6 +/- 0.3
      years) according to WHO criteria, including the examination of sealants. Mean
      DMFT increased from 1.78 (+/- 2.15) to 3.97 (+/- 3.68), mean DMFS from 2.79 (+/
      4.07) to 6.94 DMFS (+/- 8.34), respectively. Logistic regression analysis showed
      that high caries incidence at the individual level was mostly associated with the
      type of school ('Gymnasium', RR = 0.3), gender (female, RR = 2.08) and high
      baseline DMFS (RR = 1.2 per surface), but not with the number of sealants. In an
      interaction model, adolescents with high baseline DMFS values had an even higher
      risk of caries increment with an increasing number of sealants compared to
      adolescents with fewer sealants (p = 0.047). At the tooth level, this effect was
      detected for first permanent molars, while sealants in premolars and second
      permanent molars did not result in a statistically significant caries-preventive
      effect due to the low caries incidence on these surfaces. Thus, sealants on
      occlusal surfaces of first permanent molars were only protective in individuals
      with low or moderate caries activity (p = 0.006), which indicates the need for
      other measures to reduce caries activity in high risk adolescents. In addition,
      rates of 19% lost sealants and 18% carious or filled surfaces in 3 years suggest
      a discrepancy between sealant retention under real-life conditions and the
      results of controlled clinical trials.

PMID- 16946605
TI  - Efficacy of sealing proximal early active lesions: an 18-month clinical study
      evaluated by conventional and subtraction radiography.
AB  - This study assessed the efficacy of sealing proximal lesions on adult patients
      using a split-mouth design. Eighty-two 15- to 39-year-olds from the Dental
      Faculties in Copenhagen and Bogota participated, each having 2 or more proximal
      lesions in the following radiographic stages: (1) lesion restricted to the outer
      half of enamel; (2) lesion from the inner half of enamel including the enamel
      dentine junction, and (3) lesion restricted to the outer third of dentine.
      Standardized geometrically aligned baseline and follow-up radiographs were
      obtained. One randomly selected lesion (test) in each patient was sealed with 1
      of 2 resins. The patients were instructed to floss all the proximal lesions 3
      times per week. The baseline to 18 months difference in caries lesion progression
      status was assessed using 3 methods: (1) radiographs were independently assessed
      visually; (2) radiographs were read in pairs, and (3) using subtraction
      radiography of digitized images. A total of 72 subjects finished the study (12.2%
      dropout). The compliance concerning flossing was poor (15%). For the repeated
      examinations kappa was 0.84 for the visual examination, 0.44 for the paired
      readings and 0.84 for the subtraction examination. Two test lesions and 1 control
      lesion were restored. For the independent radiograph assessment method 10 and 26%
      progressed in the test and control group, respectively (p > 0.05); with the
      paired radiograph method the corresponding data were 22% in the test and 47% in
      the control groups (p < 0.01). By subtraction radiography 44% of the test group
      and 84% of the control were judged to have progressed (p < 0.001). The sealing
      technique was superior to instructing patients to floss, and subtraction
      radiography appeared to be the most sensitive method for assessing lesion
      progression.

PMID- 16946606
TI  - Three-year evaluation of the ART approach in Class III and V restorations in
      permanent anterior teeth.
AB  - This study evaluated the survival of class III and V restorations using the
      atraumatic restorative treatment (ART) approach in permanent anterior teeth,
      after 3 years. A total of 151 restorations were performed in 60 patients. After 3
      years, 107 restorations (47 patients) were evaluated. Data were analyzed using
      exact 95% confidence interval. A total of 97 restorations (91% with 95% CI = 83
      99), 76 class III (92% with 95% CI = 82-100) and 21 class V (88% with 95% CI = 77
      98) were classified as successful. The survival rate of the ART approach in class
      III and V restorations in permanent anterior teeth was considered high.

PMID- 16946607
TI  - Xylitol concentration in saliva and dental plaque after use of various xylitol
      containing products.
AB  - The study consisted of two sets of experiments, one in saliva and one in dental
      plaque. The xylitol concentration in saliva was determined enzymatically in 12
      children (mean age 11.5 years) after a standardised use of various xylitol
      products: (A) chewing gums (1.3 g xylitol), (B) sucking tablets (0.8 g xylitol),
      (C) candy tablets (1.1 g xylitol), (D) toothpaste (0.1 g xylitol), (E) rinse (1.0
      g xylitol), and (F) a non-xylitol paraffin. Unstimulated saliva was sampled 1, 3,
      8, 16 and 30 min after use. The concentration in dental plaque was determined
      after mouthrinses with contrasting amounts of xylitol (LX = 2.0 g, HX = 6.0 g,
      and control) and supragingival plaque was collected and pooled after 5, 15 and 30
      min. The mean xylitol concentration in saliva at baseline was approximately 0.1
      mg/ml. All xylitol-containing products resulted in significantly increased levels
      (p < 0.05) immediately after intake and remained elevated for 8-16 min in the
      different groups. The highest mean value in saliva was obtained immediately after
      use of chewing gums (33.7 +/- 16.4 mg/ml) and the lowest was demonstrated after
      using toothpaste (8.2 +/- 4.9 mg/ml). No significant differences were
      demonstrated between chewing gums (A), sucking tablets (B), candy (C) and rinses
      (E). In dental plaque, the mean values were 8.6 +/- 5.4 and 5.1 +/- 4.0 mg/ml 5
      min after HX and LX rinses. Concerning the higher concentration, the values
      remained significantly elevated (p < 0.05) during the entire 30-min follow-up. In
      conclusion, commonly advocated xylitol-containing products gave elevated
      concentrations of xylitol in unstimulated whole saliva and dental plaque for at
      least 8 min after intake.

PMID- 16946608
TI  - Microbiological assessment of occlusal brown-spot lesions in primary molars.
AB  - Conventional cultural methods were used to compare the plaque flora and the level
      of infection of the dentine underlying 51 occlusal brown-spot lesions and 21
      sound occlusal sites on the primary dentition. Freshly extracted primary molar
      teeth were used, and occlusal brown-spot lesions and sound occlusal sites were
      identified using laser fluorescence (LF) and clinical visual methods. A
      standardized plaque sample was taken from each site, and an LF score was recorded
      for one discrete site per tooth. The teeth were carefully opened at each
      predetermined site to determine the clinical status of the underlying dentine,
      and samples were collected using a sterile bur. The microbiota of the plaque and
      dentine samples were enumerated and identified. The mean LF scores for the sound
      sites and brown-spot lesions were 1.2 and 30.5 (p < 0.001), and all the sound
      sites exhibited hard sound dentine, but 6 out of 51 brown spots exhibited
      softened dentine. Overall there was no significant (p > 0.1) difference between
      the level of infection of the dentine of the sound and brown-spot sites, although
      some sites in the brown-spot lesions yielded high numbers of bacteria. However,
      the numbers of bacteria as log10(CFU per sample + 1) +/- SE recovered from the
      plaque above the brown-spot lesions were significantly greater than above the
      sound sites, i.e. 2.89 +/- 0.24 and 0.89 +/- 0.33, respectively. These data
      indicate that brown-spot lesions may be more plaque retentive than sound sites
      and that they are either arrested or arresting lesions, which may require
      preventive intervention.

PMID- 16946609
TI  - Statherin and histatin 1 reduce parotid saliva-promoted Streptococcus mutans
      strain MT8148 adhesion to hydroxyapatite surfaces.
AB  - Small salivary phosphoproteins--statherin (ST) and histatin 1 (HT1) - are found
      in the acquired enamel pellicle which modulates Streptococcus mutans adhesion
      onto dental enamel. However, their roles in S. mutans adhesion onto enamel
      surfaces are still undefined. The aim of this study was to investigate whether
      and how ST and HT1 affect (i) S. mutans adhesion and (ii) the adsorption of S.
      mutans adhesion-promoting salivary proteins onto hydroxyapatite (HA) in vitro. We
      fractionated human parotid saliva by adsorption to HA and further by gel
      filtration chromatography. Adhesion of [3H]-labeled S. mutans strain MT8148 onto
      sintered HA plates was promoted significantly (>10-fold) by high-molecular weight
      glycoprotein fraction (HMWGP), but not by purified ST or HT1. More interestingly,
      promotion of S. mutans adhesion onto HA by HMWGP was significantly reduced by
      adding purified ST or HT1 to HMWGP. [3H]-labeled S. mutans adhesion on HA was
      positively correlated to the [14C]-labeled HMWGP adsorption onto HA, which was
      also reduced by the addition of purified ST and HT1. Synthetic peptides
      corresponding to ST and HT1 reduced the parotid saliva-promoted S. mutans
      adhesion. However, removal of the negative charges in the N-terminal domains of
      ST and HT1 diminished their inhibitory effects on S. mutans adhesion promoted by
      parotid saliva. We conclude that ST and HT1 competitively inhibit the adsorption
      of salivary HMWGP, and thereby reduce S. mutans adhesion onto HA surfaces.

PMID- 16946610
TI  - Effects of human milk on adhesion of Streptococcus mutans to saliva-coated
      hydroxyapatite in vitro.
AB  - Adhesion of bacteria to pellicle-coated tooth surfaces is the first step in
      biofilm formation on teeth. The aim of this study was to explore whether human
      milk prevents or promotes adhesion of cariogenic Streptococcus mutans to saliva
      coated hydroxyapatite (HA) using an in vitro model system. S. mutans binding to
      HA coated with human parotid saliva (s-HA) or human milk was studied, in addition
      to binding inhibition to s-HA by human milk. S. mutans did not bind to HA coated
      with milk. S. mutans binding to s-HA was inhibited by milk from 15 (71 %) of 21
      women, whereas milk from the remaining 6 mothers enhanced binding of S. mutans to
      s-HA. Inhibition of S. mutans binding correlated with bacterial binding to s-HA
      (r = 0.76). Human milk does not mediate adhesion of S. mutans to HA in vitro, but
      affects adhesion in an individually varying fashion. Phenotypic variations in
      milk and saliva glycosylation may explain the inhibitory capacity and possibly
      affect susceptibility to colonization by S. mutans in childhood.

PMID- 16946611
TI  - Effect of Weissella cibaria isolates on the formation of Streptococcus mutans
      biofilm.
AB  - The objective of this study was to isolate and identify lactic acid bacteria able
      to inhibit the in vitro formation of Streptococcus mutans biofilm as well as the
      in vivo formation of oral biofilm. Two strains, CMS1 and CMS3, exhibiting
      profound inhibitory effects on the formation of S. mutans biofilm and the
      proliferation of S. mutans, were isolated from children's saliva and identified
      as Weissella cibaria by 16S rDNA sequencing. The water-soluble polymers produced
      from sucrose by the W. cibaria isolates also inhibited the formation of S. mutans
      biofilm. According to the results of thin-layer chromatographic analysis, the
      hydrolysates of water-soluble polymers produced by the isolates were identical to
      those of dextran, forming mostly alpha-(1-6) glucose linkages. In the clinical
      study, the subjects mouthrinsed with a solution containing W. cibaria CMS1
      evidenced plaque index reduction of approximately 20.7% (p < 0.001). These
      results indicate that the W. cibaria isolates possess the ability to inhibit
      biofilm formation, both in vitro and in vivo.

PMID- 16946612
TI  - Quantification of dental fluorosis using fluorescence imaging.
AB  - Fluorescence imaging hardware and software have been recently employed to assess
      demineralization due to early dental caries. Dental fluorosis also presents as
      diffuse surface hypomineralization of enamel and in principle similar measurement
      methods might be applicable to both. The caries analysis system requires the user
      to select an area of sound enamel around the lesion so that the affected surface
      can be reconstructed and the lesion subtracted. Whereas early caries presents as
      discrete isolated lesions fluorosis is characterized by diffuse opacities
      covering most of the tooth. Consequently it is difficult to use commercial QLF
      software for the assessment of fluorosis, as there is typically no sound area of
      enamel to use for reconstruction. This study describes a fluorescent imaging
      device capable of recording digital images of the anterior teeth and also
      software that is able to objectively measure fluorosis area and severity. A
      convenience sample of 26 subjects with a range of fluorosis from TF scores 0-3
      took part in the study. The upper left central incisor of these subjects was
      scored for fluorosis using the TF index, photographed using a conventional
      digital camera and imaged using the fluorescence imaging device. The TF index was
      then used to visually score the digital photographs and the fluorescence images.
      The data from the fluorescence method demonstrated a strong correlation with TF
      scores from fluorescence images (Kendall's tau = 0.862). The fluorescence imaging
      method shows promise as an objective, potentially blinded system for the
      longitudinal assessment of enamel fluorosis in vivo.

PMID- 16946613
TI  - Influence of fluoride-releasing restorative material on root dentine secondary
      caries in situ.
AB  - The usefulness of fluoride-releasing restorations in secondary caries prevention
      may be questioned because of the presence of other common sources of fluoride and
      because of ageing of the restorations. This study tested the hypothesis that
      glass-ionomer cement restorations, either aged or unaged, do not prevent
      secondary root caries, when fluoride dentifrice is frequently used. Sixteen
      volunteers wore palatal appliances in two phases of 14 days, according to a 2 x 2
      crossover design. In each phase the appliance was loaded with bovine root dentine
      slabs restored with either glass-ionomer or resin composite, either aged or
      unaged. Specimens were exposed to cariogenic challenge 4 times/day and to
      fluoridated dentifrice 3 times/day. The fluoride content in the biofilm (FB)
      formed on slabs and the mineral loss (DeltaZ) around the restorations were
      analysed. No differences were found between restorative materials regarding the
      FB and the DeltaZ, for either aged (p = 0.792 and p = 0.645, respectively) or
      unaged (p = 1.00 and p = 0.278, respectively) groups. Under the cariogenic and
      fluoride dentifrice exposure conditions of this study, the glass-ionomer
      restoration, either aged or unaged, did not provide additional protection against
      secondary root caries.

PMID- 16946614
TI  - The protective effect of TiF4, SnF2 and NaF on erosion of enamel by hydrochloric
      acid in vitro measured by white light interferometry.
AB  - The purpose of this in vitro study was to compare the protective effect of TiF4,
      SnF2 and NaF (all 0.5 M F) on the development of erosion-like lesions in human
      dental enamel. Four enamel specimens from each of 6 extracted molars were
      polished and embedded in epoxy resin. The enamel surfaces of 3 specimens from
      each tooth were treated with the different fluoride solutions for 2 min.
      Following fluoride treatments, the specimens were immersed in 0.01 M HCl (pH
      2.0), for 2, 4 and 6 min in order to mimic a gastric reflux situation. One
      specimen from each tooth was used as a control and was only exposed to acid. The
      etching depths (in micrometres) after 6 min were: TiF4 0.8 (SD 0.8), SnF2 3.5 (SD
      0.7), NaF 5.3 (SD 0.4), and 7.0 (SD 0.3) for the control specimens. Compared to
      the control, TiF(4) protected the enamel surface from acid attack almost
      completely (88%), while SnF2 reduced the etch depth after 6 min by 50% and NaF by
      25%.

PMID- 16946615
TI  - Increased salivary fluoride concentrations after post-brush fluoride rinsing not
      reflected in dental plaque.
AB  - The aim of the present study was to assess fluoride concentrations in
      unstimulated saliva and buccal dental plaque 6 h after an oral hygiene procedure
      that consisted of brushing with an AmF/SnF2 dentifrice and different post-brush
      rinsing protocols: expectorating the excess of dentifrice foam and rinsing with
      tap water, expectorating only, or rinsing with 10 ml AmF/SnF2 mouthwash. The
      fluoride concentrations in plaque and saliva were increased after all three
      experimental protocols compared to F-free periods. The increase of the fluoride
      concentration in saliva was more pronounced after AmF/SnF2 mouthrinse as compared
      to rinsing with water and expectorating the excess of dentifrice foam. Such an
      effect was not seen in dental plaque. It is concluded that the potentially
      beneficial effect of not rinsing or fluoride rinsing after tooth brushing is not
      reflected in an increased fluoride concentration in newly formed dental plaque 6
      h after brushing.

PMID- 16946616
TI  - Salivary fluoride from fluoride dentifrices or rinses after use of a calcium pre
      rinse or calcium dentifrice.
AB  - The low concentration of available calcium (Ca) in oral fluids limits the
      formation of Ca-mediated fluoride deposits that maintain oral fluoride (F) after
      a topical F treatment. The purpose of this study was to examine if a high
      concentration of Ca would increase salivary F when used before a F rinse or
      dentifrice. We found that a Ca pre-rinse (150 mmol/l Ca lactate) or Ca dentifrice
      (0.084 g Ca glycerolphosphate per gram dentifrice) used immediately before a 60 s
      228-ppm F rinse (12 mmol/l NaF) produced a 4.6x or 3.6x increase (p < 0.05)
      respectively in the 1 h salivary F concentrations over the F rinse alone.
      Reducing the post-Ca F rinse to 10 s still produced a significant 2.2x increase
      in salivary F compared to the 60 s F rinse alone. Used with a conventional 1,100
      ppm F (i.e. 1,100 microg F per gram) NaF dentifrice (Crest), the above Ca pre
      rinse increased 1 h salivary F levels by 2.3x over the F dentifrice alone.
      However, a F rinse given before a Ca rinse produced no increase in 1 h salivary F
      concentrations. Although the persistence of these increases requires further
      study, these results suggest that a moderately high concentration of Ca given
      shortly before a F rinse or F dentifrice may increase the cariostatic effect of
      the F product.

PMID- 16946617
TI  - White matter ischemia: Time to begin integrating experimental and clinical data.

PMID- 16946618
TI  - Recent biochemical advances in white matter ischaemia.
AB  - Stroke is one of the leading causes of death and disability in the developed
      world and as a result is the focus of intensive research. Historically,
      investigators in the field have focused on the effects of energy deprivation on
      the neuronal population, but, in recent times, as imaging techniques have become
      more advanced, a greater appreciation of the extent of non-neuronal injury has
      emerged. Initial investigations into the pathophysiology of white matter
      ischaemia reported damage to central myelinated axons via reversal of the Na+
      Ca2+ exchange protein due to Na+ loading and ischaemia-induced membrane
      depolarisation. The latter also gates voltage-sensitive Ca2+ channels that
      contribute to the Ca2+ overload both directly and indirectly via Ca2+ release
      from intracellular stores. Excitotoxicity, once thought the unfortunate preserve
      of neurons, also contributes to white matter damage via both N-methyl-D-aspartate
      (NMDA) and non-NMDA glutamate receptors. However, important physiological
      differences are apparent in these receptors when compared to those present at the
      synapse, leading researchers to ask whether the molecular diversity of glutamate
      receptors will provide successful therapeutic interventions in the future. This
      brief review aims to summarise recent progress in the field of white matter
      ischaemia.

PMID- 16946619
TI  - Hypercalcaemia in relapsed medulloblastoma 8 years post-diagnosis; evidence to
      support PTHrP production by medulloblastoma cells.
AB  - BACKGROUND: A 19-year-old male presented with symptomatic hypercalcaemia as the
      first manifestation of relapsed metastatic medulloblastoma. Management at the
      time of the initial presentation 8 years earlier was with surgical excision and
      craniospinal radiotherapy. His biochemistry at the time of relapse and studies of
      medulloblastoma cell lines provide an insight into the pathogenesis of his
      hypercalcaemia. METHODS: Parathyroid hormone-related protein (PTHrP) was measured
      by immunoradiometric assay in blood, and in conditioned and control media from
      three medulloblastoma cell lines following 72 h growth. RESULTS: The histology at
      initial presentation (11 years of age) and at the time of relapse (with bone
      marrow infiltration and widespread bony metastases) demonstrated medulloblastoma.
      Ionised calcium concentrations at relapse were 2.89 mmol/l and serum PTHrP levels
      were increased at the same time (2.7 pmol/l; normal range: 0.7-1.8 pmol/l). There
      was evidence of PTHrP production by one cell line (MHH-MED-8A) while results for
      both other lines tested were below the limit of detection. CONCLUSIONS: Relapse 8
      years after diagnosis is unusual in medulloblastoma and for this relapse to
      manifest as hypercalcaemia is also very uncommon. Our investigations suggest that
      the clinical picture was a reflection of PTHrP production by medulloblastoma
      cells.

PMID- 16946620
TI  - A girl with a novel splice site mutation in VDR supports the role of a ligand
      independent VDR function on hair cycling.
AB  - Mutations in vitamin D receptor (VDR) cause hereditary vitamin D resistant
      rickets (HVDRR). We reported a Thai girl with HVDRR, presenting with an early
      onset of rickets and partial alopecia. She was a product of a consanguineous
      couple. Mutation analysis showed that she was homozygous for a novel splice site
      mutation of the VDR gene, 462 + 1 G --> C, resulting in incorporation of the
      whole 254 bp of the intron 4 into its mRNA. The mutated protein is expected to
      contain no ligand-binding domain. The fact that she did not develop total
      alopecia despite of no VDR ligand-binding domain supports that VDR function on
      hair cycling is ligand independent.

PMID- 16946621
TI  - Psychosocial functioning, self-perception and body image and their auxologic
      correlates in growth hormone and oestrogen-treated young adult women with Turner
      syndrome.
AB  - BACKGROUND: Few data are available on the psychosocial status of growth hormone
      (GH) and oestrogen treated women with Turner syndrome (TS). In this study, we
      evaluated psychosocial functioning, self-concept and body image in GH and
      oestrogen treated young adult women with TS and we studied the relationship with
      auxological parameters. PATIENTS AND METHODS: Thirty women with TS (mean +/- SD
      age: 22.1 +/- 2.4 years), all treated with GH and oestrogens if indicated, and an
      age-matched reference group of 44 non-Turner female students (age: 20.5 +/- 2.1
      years) completed 3 questionnaires evaluating, respectively, behavioural and
      emotional problems (Young Adult Self Report), self-concept (Self Perception
      Profile for College Students) and body-image (Body Attitude Scale). RESULTS: TS
      patients did not report more behavioural and emotional problems compared to the
      non-TS females except for attention problems; they even reported fewer problems
      on some subscales (somatic complaints, thought problems, delinquent behaviour).
      TS patients did not differ from the non-TS female group in their bodily
      satisfaction. TS patients, particularly patients with a 45,X karyotype, perceived
      themselves as less socially competent. BMI was significantly related to the
      appraisal score of the Body Attitude Scale, whereas height was not related to any
      of the evaluated psychosocial parameters. CONCLUSION: The psychosocial adaptation
      of young adult women with TS, diagnosed at an early age and treated during
      childhood with GH and oestrogens if indicated, appears to be quite satisfactory.
      Follow-up of adult TS patients should not neglect the problem of overweight and
      associated psychosocial consequences.

PMID- 16946622
TI  - Effect of reproductive factors and postmenopausal hormone use on the risk of
      amyotrophic lateral sclerosis.
AB  - OBJECTIVE: To examine the associations of reproductive factors and postmenopausal
      hormone use with the risk of amyotrophic lateral sclerosis (ALS) among women.
      METHODS: This case-control study was conducted within the Kaiser Permanente
      Medical Care Program (KPMCP) of Northern California during the years 1996-2000.
      Among the 193 postmenopausal women, 62 were incident ALS cases and 131 were
      controls randomly selected from KPMCP members and frequency matched by age and
      respondent type (self versus proxy) to the cases. Statistical analyses were
      carried out using logistic regression. RESULTS: Reproductive factors such as age
      at menarche, age at final menstrual period, parity, oral contraceptive use, and
      type of menopause (natural vs. hysterectomy with or without oophorectomy) were
      not associated with risk of ALS. Postmenopausal hormone use was positively, but
      not significantly, associated with the risk of ALS (adjusted OR 1.9, 95% CI 0.9
      3.8). CONCLUSIONS: Reproductive factors were not associated with ALS risk. There
      is no evidence that suggests a protective effect of postmenopausal hormone use
      against the development of ALS. However, due to insufficient power, we cannot
      rule out a possible increase in ALS risk associated with postmenopausal hormone
      use.

PMID- 16946623
TI  - Combined work and leisure physical activity and risk of stroke in men and women
      in the European prospective investigation into Cancer-Norfolk Prospective
      Population Study.
AB  - Most studies to date support a protective role of physical activity in reducing
      stroke risk. However, they were not able to take into account combined work and
      leisure activity. We prospectively followed up 22,602 men and women aged 40-79
      years, who had no history of stroke and myocardial infarction at baseline,
      participating in the European Prospective Investigation into Cancer-Norfolk.
      Participants were categorized into four levels of physical activity based on a
      validated self-reported questionnaire, which assesses combined work and leisure
      activities, at baseline during the period from 1993 to 1997. Stroke incidence was
      ascertained by death certificate and hospital record linkage data up to 2004,
      average 8.6 years of follow-up. We used the Cox proportional hazards model. There
      were 361 incident strokes during follow-up (total person years = 195,092). After
      adjusting for age, sex, systolic blood pressure, body mass index, cholesterol,
      history of diabetes and smoking, men and women who were physically active were
      less likely to have a stroke (relative risk = 0.70, 95% CI: 0.49-0.99, p = 0.024)
      compared to those who were inactive. This highlights the fact that efforts to
      increase physical activity in both the work place and in leisure time should be
      encouraged.

PMID- 16946624
TI  - Amyotrophic lateral sclerosis and exposure to environmental toxins: an Australian
      case-control study.
AB  - It has been suggested that environmental toxins could be risk factors for
      sporadic amyotrophic lateral sclerosis (SALS). We therefore analysed
      epidemiological data on 179 SALS cases and 179 age-, ethnicity- and sex-matched
      controls in Australia using self-reporting questionnaires. SALS was associated
      with solvent/chemical exposure (OR = 1.92, 95% CI: 1.26-2.93), overall
      herbicide/pesticide exposure (OR = 1.57, 95% CI: 1.03-2.41) and industrial
      herbicide/pesticide exposure (OR = 5.58, 95% CI: 2.07-15.06). Exposure to
      herbicides/pesticides showed a dose-response effect. All positive findings were
      more statistically significant in males. These findings support those from
      northern hemisphere studies, indicating that environmental toxins can be risk
      factors for SALS.

PMID- 16946625
TI  - Morphine state-dependent learning sensitization and interaction with nitric
      oxide.
AB  - In the present study, the effects of nitric oxide (NO) precursor L-arginine and L
      NAME, a potent inhibitor of NO synthase (NOS), on the expression of sensitization
      of morphine were investigated. Pre-training administration of morphine (5 mg/kg)
      impaired memory retrieval compared to pre-training saline-treated animals.
      Amnesia due to pre-training morphine (5 mg/kg) was restored by pre-test morphine
      (5 mg/kg). The retrieval impairment was also inhibited in mice which had received
      once-daily injections of morphine (20 and 30 mg/kg, s.c.) for 3 days, followed by
      5 days of no drug treatment before training (in order to induce morphine
      sensitization). Administration of L-arginine (60 mg/kg/day - 3 days) or L-NAME
      (20 mg/kg/day - 3 days) before training did not alter morphine state dependency.
      During acquisition of sensitization, administration of L-arginine (60 mg/kg) 20
      min before morphine (10 mg/kg/day, for 3 days) increased, while injection of L
      NAME (20 mg/kg) 20 min before morphine (30 mg/kg/day, for 3 days) decreased
      morphine state dependency. It is concluded that NO is involved in the morphine
      induced sensitization.

PMID- 16946627
TI  - Medical complications of surgical treatment of adult spinal deformity and how to
      avoid them.
AB  - STUDY DESIGN: Review article of medical complications related to adult spinal
      deformity surgery. OBJECTIVE: To identify medical complications related to
      surgery for adult spinal deformity and suggest ways to minimize their occurrence
      and to avoid them. SUMMARY OF BACKGROUND DATA: Medical complications are a major
      consideration in adult spinal deformity surgery. Few studies have been done to
      identify the medical complication rate in relation to these procedures. METHODS:
      We review the literature pertaining to medical complications regarding spinal
      deformity surgery. RESULTS: Urinary tract infections are the most frequently seen
      complication. Additionally, pulmonary complications are the most common life
      threatening complication. Medical complications are a frequent occurrence with
      adult deformity spinal surgery. CONCLUSIONS: Awareness of the presentation,
      treatment, and prevention of medical complications of deformity surgery may allow
      minimization of their occurrence and optimize treatment should they occur.

PMID- 16946628
TI  - The SRS classification for adult spinal deformity: building on the King/Moe and
      Lenke classification systems.
AB  - STUDY DESIGN: Descriptive study of the Scoliosis Research Society (SRS)
      Classification for Adult Spinal Deformity using interobserver reliability
      measures for validation of the system. OBJECTIVES: To propose and validate a
      classification system for adult spinal deformity that will have utility in
      reporting on treatment options and outcomes for affected adults. SUMMARY OF
      BACKGROUND DATA: Classification systems exist for adolescent idiopathic scoliosis
      and have utility in categorizing spinal deformity and guiding choices for
      management. Adult spinal deformity is distinct from adolescent deformity.
      Important distinctions include present impairment and pain, regional and global
      decompensation, and degenerative changes within the deformity. A useful
      classification system for adult spinal deformity does not exist. The absence of a
      classification system for adult deformity compromises the ability to report on
      similar cases and to develop an evidence-based approach to care. METHODS:
      Descriptive study design with development of an SRS Classification System using
      the Delphi Method. Validation of the system using interobserver reliability
      measures based on responses of SRS-member surgeons to radiographic case
      presentations. RESULTS: Nineteen surgeons evaluated 25 cases of adult spinal
      deformity. Interobserver reliability for curve types (kappa = 0.64), regional
      sagittal modifiers (kappa = 0.73), and degenerative lumbar modifiers (kappa =
      0.65) were substantial. Interobserver reliability was moderate (kappa = 0.56) for
      choosing a cephalad level for operative treatment and substantial for choosing a
      caudad level (kappa = 0.77). CONCLUSIONS: A uniform system for classification of
      adult spinal deformity has significant utility in improving the ability of
      surgeons and authors to compare and combine similar cases, and in improving the
      accuracy of reports on the outcomes of care for adults with spinal deformity. The
      SRS Classification System for Adult Spinal Deformity has good interobserver
      reliability and is predictive of surgical strategies. Further validation of the
      SRS Classification System will include measures of intraobserver reliability, and
      inclusion of clinical characteristics of patient presentation and comorbidities.

PMID- 16946629
TI  - Preparing the adult deformity patient for spinal surgery.
AB  - STUDY DESIGN: Review article of preoperative evaluation of surgical patients as
      relates to adult spine patients. OBJECTIVE: To determine which patients should
      undergo preoperative evaluation and review options for improved preoperative
      preparation for these patients. SUMMARY OF BACKGROUND DATA: There is increasing
      attention paid to preoperative preparation for surgical patients to decrease
      perioperative morbidity. Better preoperative evaluation may lead to decreased
      complication rates and may improve outcomes. METHODS: The literature to date,
      including surgical, hospitalist, and critical care, was reviewed and combined
      with the authors' experience. RESULTS: Suggestions for preoperative screening
      questions are summarized. CONCLUSION: Better recognition of preoperative risk
      factors may help spine surgeons improve preoperative preparation in their
      patients, leading to decreased complication rates.

PMID- 16946630
TI  - Principles for selecting fusion levels in adult spinal deformity with particular
      attention to lumbar curves and double major curves.
AB  - STUDY DESIGN: Review article. OBJECTIVES: To identify decision-making principles
      for selecting fusion levels in adult spinal deformity, with particular attention
      to lumbar curves and double major curves. SUMMARY OF BACKGROUND DATA: Although
      numerous articles have been published on the selection of fusion levels for
      adolescent idiopathic scoliosis (AIS) curves, relatively less attention has been
      paid to the selection of fusion levels for the operative management of adult
      scoliosis. METHODS: This is a literature review pertaining to the surgical
      management of adult scoliosis. RESULTS: Selection of fusion levels for adult
      scoliosis can be difficult; however, certain biomechanical and surgical
      principles can consistently be applied. CONCLUSION: An appreciation of both the
      coronal and sagittal plane components of spinal deformity is mandatory to achieve
      optimal results with surgical stabilization of adult scoliosis.

PMID- 16946631
TI  - Considerations for focused surgical intervention in the presence of adult spinal
      deformity.
AB  - STUDY DESIGN: Case studies, literature review. OBJECTIVES: The goal of this
      review is to raise awareness and stimulate contributions on this topic. SUMMARY
      OF BACKGROUND DATA: Surgical management of adult patients presenting with
      intractable back and leg pain in conjunction with spinal deformity often raises
      the question of need for curve arthrodesis. Meticulous patient assessment is
      essential in determining if the deformity underlies patient symptoms. If so, then
      the deformity must be stabilized according to criteria established in the
      literature. However, when patient evaluation suggests that the deformity is not
      the source of symptoms, other surgical options may be considered. These include
      limited decompression without fusion or decompression with short fusion limited
      only to the site of pathology. MATERIALS AND METHODS: Three cases are presented
      illustrating situations where decompression alone or decompression with short
      fusion was indicated. RESULTS: When an adult spinal deformity is stable and is
      not the source of symptoms, symptomatic relief may be provided through limited
      decompression within the curve but without curve arthrodesis. Similarly,
      symptomatic pathology arising from levels adjacent to or remote from the
      deformity may be addressed with short-segment decompression and fusion.
      CONCLUSIONS: This brief and limited communication reviews some of the pertinent
      issues and provides several examples of selective surgical treatment options
      without curve arthrodesis in patients with deformity. These options are typically
      much smaller surgical undertakings, particularly in adult patients who generally
      have complicating comorbidities. Little has been published to guide surgical
      management for these conditions.

PMID- 16946632
TI  - Instrumentation-related complications of multilevel fusions for adult spinal
      deformity patients over age 65: surgical considerations and treatment options in
      patients with poor bone quality.
AB  - STUDY DESIGN: Retrospective follow-up of patients over the age of 65 with a
      minimum of five-level fusions. OBJECTIVE: To determine the effect on outcomes of
      long constructs in patients with poor bone stock, and to review surgical
      techniques used in patients with poor bone stock. SUMMARY OF BACKGROUND DATA:
      Scoliotic deformities in patients with poor bone stock require alterations in
      both the surgical technique and preoperative planning. To our knowledge,
      complications of long constructs in poor bone stock have not been specifically
      reported. METHOD: Patients over the age of 65 that underwent a minimum of five
      level fusion over a 5-year period were reviewed. We reviewed both operative
      reports and clinic notes and recorded both early and late complications. RESULTS:
      Early complications included pedicle fractures and compression fractures with an
      overall rate of 13%. Late complications included pseudarthroses with
      instrumentation failure, adjacent level disc degeneration with herniation,
      compression fractures, and progressive kyphosis. Progressive junctional kyphosis
      occurred in 26% of patients. CONCLUSIONS: Spinal stabilization surgery in
      patients with poor bone stock is associated with high complication rates.
      Complications such as progressive kyphosis adjacent to the fusion are difficult
      to address with instrumentation alone.

PMID- 16946633
TI  - Biomechanical analysis of rotational motions after disc arthroplasty:
      implications for patients with adult deformities.
AB  - STUDY DESIGN: An anatomic and biomechanical bench-top basic scientific
      comparative analysis to determine the appropriateness of total disc replacement
      (TDR) in a lumbar spine with scoliotic tendencies. OBJECTIVES: Only limited data
      are currently available studying the application of disc replacement adjacent to
      scoliosis fusions. Theoretically, motion preservation should help delay the
      continuum of lumbar degeneration adjacent to scoliosis fusions and rotationally
      unstable lumbar segments. SUMMARY OF BACKGROUND DATA: As a tertiary referral
      center for failed TDR, we noticed an alarming number of lumbar spinal rotational
      iatrogenic instability patterns but none occurring in the cervical spine. It is
      appropriate to analyze the bench-top rotational stability of disc replacement to
      predict whether this new technology is feasible for a larger prospective clinical
      study in the treatment of degenerative scoliosis. METHODS: Measurements were
      taken from 60 human specimens from the Hamann-Todd Osteological Collection: 1) to
      determine the rotational arc of influence (AOI) = the angle formed from the
      center of axial rotation to the outermost extent of the facet joints; and 2) to
      determine the relative anatomic size discrepancy between the left and right
      facets proportionately with the cross-sectional area of the intervertebral disc =
      facet/endplate ratio (FER). Biomechanical testing was performed using fresh
      frozen human cadaveric spines with the following conditions to determine the
      rotational stability: 1) intact; 2) resection of ALL, anulus, disc, and PLL
      simulating the preparation for a TDR; 3) a more radical anular resection; 4)
      entire 360 degrees anular resection; and 4) insertion of the respective
      unconstrained-type disc replacement. Using a 6 degrees of freedom spine
      simulator, unconstrained pure moments of +/-8.0 Nm (lumbar) and +/-3.0 Nm
      (cervical) were used for axial rotation with quantification of the operative
      level range of motion and neutral zone, with data normalized to the intact spine
      condition. RESULTS: There were anatomic limitations in the lumbar spine that make
      it less desirable to apply uncon-strained disc replacements; indeed, the spine
      was at risk for iatrogenic lumbar scoliosis. The anulus fibrosis, anterior
      longitudinal ligament, and the posterior longitudinal ligament are critical
      structures in preventing iatrogenic scoliosis. The lumbar facet joints are more
      posteriorly located and are smaller relative to the intervertebral disc, compared
      with this association in the cervical spine. Because the facet capsular ligaments
      are mechanically less effective with lower tensile strength in the lumbar spine,
      multiple-level arthroplasty tends to accentuate scoliotic tendencies; this is
      independent of prosthetic design and surgical technique. DISCUSSION: Implantation
      of the lumbar TDR never restored the motion segment back to the rotational
      stability of the intact segment achieving a range of 120% to 140% rotational
      range of motion compared with the intact condition. This rotational instability
      proved to be additive as a two-level lumbar TDR resulted in between 240% and 260%
      increase in rotational instability compared with the intact condition.
      CONCLUSION: The neutral zone of the intact cervical spine was restored even using
      an unconstrained cervical TDR. The greater inherent rotational constraints of the
      cervical spine make it more amenable to stable multilevel arthroplasty compared
      with the lumbar spine.

PMID- 16946634
TI  - Thoracic and thoracolumbar kyphosis in adults.
AB  - STUDY DESIGN: Author experience and literature review. OBJECTIVES: To investigate
      the spectrum of adult kyphosis and to discuss the various surgical and
      nonsurgical treatment options. SUMMARY OF BACKGROUND DATA: Kyphosis with its
      various etiologies and associated pathophysiologies has been discussed in the
      literature for many decades. The nonsurgical treatment primarily consists of
      symptom reduction via physical therapy and has not changed significantly for
      decades. The surgical treatment, however, has changed dramatically. A decade ago,
      most large kyphotic deformities required anterior and posterior procedures. With
      the advent of numerous posterior osteotomy techniques and pedicle fixation, most
      of these deformities are now treated via posterior methods only. METHODS: Using
      literature review and the author's experience, kyphosis and its characteristics
      will be discussed. Important details pertinent to presurgical planning and
      execution of surgical will be discussed. Three cases will be presented to
      illustrate the surgical treatment options for three qualitatively different
      kyphotic deformities. RESULTS: Flexible kyphotic deformities may respond well to
      aggressive facetectomies and cantilever corrections. Multisegmental osteotomies
      may be most appropriate for long sweeping deformities. Fixed, sharply, angulated
      deformities may respond best to pedicle subtraction osteotomies or vertebral
      column resections. CONCLUSION: Segmental pedicle screw fixation coupled with one
      of four posterior osteotomy/resection techniques can be used to address most
      sagittal plain deformities. Careful application of these techniques is important.
      Smith-Petersen and Ponte osteotomies are most appropriate for long sweeping
      deformities with mobile anterior columns. Pedicle subtraction osteotomies and
      vertebral column resections are most appropriate for fixed, sharply angulated
      spinal deformities. The successful application of these techniques is dependent
      on accurate preoperative evaluation of the structural properties of the kyphosis
      and meticulous execution of the surgical technique.

PMID- 16946635
TI  - Decision making regarding Smith-Petersen vs. pedicle subtraction osteotomy vs.
      vertebral column resection for spinal deformity.
AB  - STUDY DESIGN: Author experience and literature review. OBJECTIVES: To investigate
      and discuss decision-making on when to perform a Smith-Petersen osteotomy as
      opposed to a pedicle subtraction procedure and/or a vertebral column resection.
      SUMMARY OF BACKGROUND DATA: Articles have been published regarding Smith-Petersen
      osteotomies, pedicle subtraction procedures, and vertebral column resections.
      Expectations and complications have been reviewed. However, decision-making
      regarding which of the 3 procedures is most useful for a particular spinal
      deformity case is not clearly investigated. METHODS: Discussed in this manuscript
      is the author's experience and the literature regarding the operative options for
      a fixed coronal or sagittal deformity. RESULTS: There are roles for Smith
      Petersen osteotomy, pedicle subtraction, and vertebral column resection. Each has
      specific applications and potential complications. CONCLUSION: As the magnitude
      of resection increases, the ability to correct deformity improves, but also the
      risk of complication increases. Therein, an understanding of potential
      applications and complications is helpful.

PMID- 16946636
TI  - Debate: to fuse or not to fuse to the sacrum, the fate of the L5-S1 disc.

PMID- 16946637
TI  - Debate: determining the upper instrumented vertebra in the management of adult
      degenerative scoliosis: stopping at T10 versus L1.

PMID- 16946638
TI  - Debate: degenerative scoliosis: to operate or not to operate.

PMID- 16946640
TI  - Randomized controlled trial of specific spinal stabilization exercises and
      conventional physiotherapy for recurrent low back pain.
AB  - STUDY DESIGN: Pragmatic, multicentered randomized controlled trial, with 12-month
      follow-up. OBJECTIVE: To evaluate the effect of adding specific spinal
      stabilization exercises to conventional physiotherapy for patients with recurrent
      low back pain (LBP) in the United Kingdom. SUMMARY OF BACKGROUND DATA: Spinal
      stabilization exercises are a popular form of physiotherapy management for LBP,
      and previous small-scale studies on specific LBP subgroups have identified
      improvement in outcomes as a result. METHODS: A total of 97 patients (18-60 years
      old) with recurrent LBP were recruited. Stratified randomization was undertaken
      into 2 groups: "conventional," physiotherapy consisting of general active
      exercise and manual therapy; and conventional physiotherapy plus specific spinal
      stabilization exercises. Stratifying variables used were laterality of symptoms,
      duration of symptoms, and Roland Morris Disability Questionnaire score at
      baseline. Both groups received The Back Book, by Roland et al. Back-specific
      functional disability (Roland Morris Disability Questionnaire) at 12 months was
      the primary outcome. Pain, quality of life, and psychologic measures were also
      collected at 6 and 12 months. Analysis was by intention to treat. RESULTS: A
      total of 68 patients (70%) provided 12-month follow-up data. Both groups showed
      improved physical functioning, reduced pain intensity, and an improvement in the
      physical component of quality of life. Mean change in physical functioning,
      measured by the Roland Morris Disability Questionnaire, was -5.1 (95% confidence
      interval -6.3 to -3.9) for the specific spinal stabilization exercises group and 
      5.4 (95% confidence interval -6.5 to -4.2) for the conventional physiotherapy
      group. No statistically significant differences between the 2 groups were shown
      for any of the outcomes measured, at any time. CONCLUSIONS: Patients with LBP had
      improvement with both treatment packages to a similar degree. There was no
      additional benefit of adding specific spinal stabilization exercises to a
      conventional physiotherapy package for patients with recurrent LBP.

PMID- 16946641
TI  - Biomechanical comparison of instrumented posterior lumbar interbody fusion with
      one or two cages by finite element analysis.
AB  - STUDY DESIGN: Using finite element models to study the biomechanics of lumbar
      instrumented posterior lumbar interbody fusion (PLIF) with one or two cages.
      OBJECTIVE: Analyzing the biomechanics of instrumented PLIF with one or two cages
      as to evaluate whether a single cage is adequate for instrumented PLIF. SUMMARY
      OF BACKGROUND DATA: Implantation of a single cage in instrumented PLIF of lumbar
      spine is still controversial. METHODS: Three validated finite element models of
      L3-L5 lumbar segment were established [intact model (INT), one cage model (LS-1),
      and two cages model (LS-2)]. The available finite element program ANSYS 6.0
      (Swanson Analysis System Inc., Houston, TX) was applied. To analyze the
      biomechanics of these models, 10 Nm flexion, extension, rotation, and lateral
      bending moment with 150 N of preload were respectively imposed on the superior
      surfaces of the L3. RESULTS: Compared with the INT model, the decrease of ROM in
      the LS-1 and LS-2 models were exaggerated from 0.67 degrees to 3.73 degrees and
      ranged from 37.2% to 86.1% in all motions. The mean subsidence was found to be
      slightly higher in the LS-1 model. Most of the cage dislodgement in both models
      was less than 0.03 mm. The mean dislodgement was slightly higher in the LS-1
      model. The stress of cage was found to be high in the LS-2 model. The mean stress
      of screw was raised to 4.5% to 9.7% in the LS-1, which was higher than that in
      the LS-2 model. In general, stress of adjacent disc was more pronounced in the LS
      2 model. The most stress distributed at the anterior portion of the adjacent
      disc, which could be used to interpret the clinical findings of the early
      adjacent disc degeneration. CONCLUSIONS: A single cage inserted in an
      instrumented PLIF gains approximate biomechanical stability, slight greater
      subsidence, and a slight increase in screw stress but less early degeneration in
      adjacent disc. Adjusting these factors, instrumented PLIF with one cage could be
      encouraged in clinical practice.

PMID- 16946642
TI  - Kinetic analysis of the cervical spinal cord in patients after spinous process
      splitting laminoplasty using a kinematic magnetic resonance imaging technique.
AB  - STUDY DESIGN: An in vivo flexion-extension magnetic resonance imaging study.
      OBJECTIVE: To evaluate the kinetic changes of the cervical spinal cord after
      laminoplasty in patients with cervical myelopathy. SUMMARY OF BACKGROUND DATA:
      Laminoplasty for cervical myelopathy increases the space occupied by the spinal
      cord, leading to a decompressive effect on the cord. However, there are few
      reports on kinetic changes of the spinal cord following this surgical procedure,
      by which it may contribute to an improvement of clinical symptoms. METHODS:
      Patients who underwent spinous process-splitting laminoplasty (n = 40) and
      control group (n = 20) were enrolled in the study. Cervical spines of the
      subjects were examined from maximum extension to maximum flexion using a magnetic
      resonance imaging scanner. Sagittal T1-weighted images were obtained at 12
      different angle positions. Images were analyzed with respect to the distance and
      alignment disparity between the dorsal edge of the vertebral column and the
      center of the cord at each disc level using National Institutes of Health Image
      software. RESULTS: Spinal cords of patients after laminoplasty were dorsally
      shifted in the enlarged spinal canal at neutral, extension, and flexion
      positions. Alignment changes of the cord during flexion-extension movements of
      the cervical spine were dissociated from those of the vertebral column because of
      smaller changes in the cord alignment. CONCLUSIONS: Spinous process-splitting
      laminoplasty increases the degree of freedom of the spinal cord.

PMID- 16946643
TI  - Spinal cord monitoring in patients with spinal deformity and neural axis
      abnormalities: a comparison with adolescent idiopathic scoliosis patients.
AB  - STUDY DESIGN: A retrospective review of spinal cord monitoring (SCM) results of
      patients with neural axis abnormalities (NAA) as compared with a control group of
      adolescent idiopathic scoliosis (AIS) patients. OBJECTIVE: To analyze SCM on a
      group of patients who had a NAA undergoing spinal deformity surgery. SUMMARY OF
      BACKGROUND DATA: To our knowledge, only 1 report in the literature has analyzed
      the accuracy and reliability of SCM in patients with NAA. METHODS: Over a 10-year
      period, 41 patients with NAA had SCM while undergoing surgery for spinal
      deformity. These patients were retrospectively compared with a group of 136 AIS
      patients. RESULTS: The average ages were similar (14.4 vs. 14.6 years), but there
      were more males (48.8% vs. 19.1%) and greater preoperative curve magnitude in the
      NAA group (65.9 degrees vs. 59.8 degrees ) (P < 0.05). Good baseline values were
      achieved less often in the NAA group for somatosensory-evoked potentials (SSEP)
      (85.4% vs. 98.5%) and motor-evoked potentials (MEP) (82.6% vs. 100%) (P < 0.05).
      Significant deviations from baseline values were seen more often in the NAA group
      for SSEP (8.6% vs. 1.5%) and MEP (5.3% vs. 2.5%). There were no false negatives
      in either group. CONCLUSIONS: SCM in patients who have NAA can be more difficult
      to obtain than in AIS but results in few false positives and does not miss
      neurologic injury.

PMID- 16946644
TI  - Effect of different upright sitting postures on spinal-pelvic curvature and trunk
      muscle activation in a pain-free population.
AB  - STUDY DESIGN: A normative within-subjects single-group study. OBJECTIVE: To
      compare spinal-pelvic curvature and trunk muscle activation in 2 upright sitting
      postures ("thoracic" and "lumbo-pelvic") and slump sitting in a pain-free
      population. SUMMARY OF BACKGROUND DATA: Clinical observations suggest that both
      upright and slump sitting postures can exacerbate low back pain. Little research
      has investigated the effects of different upright sitting postures on trunk
      muscle activation. METHODS: Spinal-pelvic curvature and surface electromyography
      of 6 trunk muscles were measured bilaterally in 2 upright (thoracic and lumbo
      pelvic) sitting postures and slump sitting in 22 subjects. RESULTS: Thoracic,
      compared to lumbo-pelvic, upright sitting showed significantly greater thoracic
      extension (P < 0.001), with significantly less lumbar extension (P < 0.001) and
      anterior pelvic tilt (P = 0.03). Furthermore, there was significantly less
      superficial lumbar multifidus (P < 0.001) and internal oblique (P = 0.03)
      activity, with significantly higher thoracic erector spinae (P < 0.001) and
      external oblique (P = 0.04) activity in thoracic upright sitting. There was no
      significant difference in superficial lumbar multifidus activity between thoracic
      upright and slump sitting. CONCLUSIONS: Different upright sitting postures
      resulted in altered trunk muscle activation. Thoracic when compared to lumbo
      pelvic upright sitting involved less coactivation of the local spinal muscles,
      with greater coactivation of the global muscles. These results highlight the
      importance of postural training specificity when the aim is to activate the lumbo
      pelvic stabilizing muscles in subjects with back pain.

PMID- 16946645
TI  - Surgical correction of developmental scoliosis following cardiac transplantation:
      case report.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To present a pediatric patient who
      underwent successful 2-stage anterior and posterior scoliosis surgery 20 months
      after cardiac transplantation. SUMMARY OF BACKGROUND DATA: Cardiac
      transplantation has increased the life expectancy in children with end-stage
      cardiac failure caused by congenital heart disease or cardiomyopathy. Scoliosis
      is commonly associated with congenital cardiac disease. Previous reports have
      suggested that anterior scoliosis surgery is contraindicated after heart
      transplantation. METHODS: We describe the case of a 13-year-old patient who
      underwent staged anterior and posterior spinal arthrodesis to correct a severe
      thoracic developmental scoliosis. RESULTS: The 2 procedures were performed 1 week
      apart. Following the first stage, pulmonary edema had developed, which required
      reintubation and administration of diuretics. Significant blood loss occurred
      during the posterior spinal fusion. The patient had a satisfactory correction of
      her scoliosis and made a good recovery. Three years after surgery, she had no
      complaints of her back and had a solid spinal fusion. CONCLUSIONS: Elective
      anterior and posterior spinal arthrodesis can be safely performed in cardiac
      transplant recipients with severe developmental scoliosis. This procedure can
      achieve optimum correction of the curvature and a successful outcome without long
      term medical or technical complications.

PMID- 16946646
TI  - Lumbosacral nerve root anomaly associated with spondylolisthesis in an
      adolescent: a case report and review of the literature.
AB  - STUDY DESIGN: Case report. OBJECTIVE: We describe the case of a lumbosacral nerve
      root anomaly in a 16-year-old male with spondylolisthesis and neurologic findings
      exceeding that that was expected of the underlying deformity. A complete review
      of clinical, radiologic, and operative records was performed. SUMMARY OF
      BACKGROUND DATA: Spondylolisthesis is a relatively common cause of lower back
      pain in adolescents. Neurologic findings may occur, most commonly associated with
      higher grade spondylolisthesis and spondyloptosis. Lumbosacral nerve root
      anomalies have been reported and are typically associated with neurologic
      symptoms in excess of the underlying deformity. METHODS: The 16-year-old male
      presented with lower back pain, difficulty walking, and sensory and motor
      symptoms in the L5 and S1 nerve root distributions. Radiographs revealed a
      Meyerding grade III spondylolisthesis, with a slip angle of 14 degrees and a
      lumbosacral angle of 76 degrees . Neither computerized tomography nor magnetic
      resonance imaging revealed the presence of lumbosacral nerve root anomalies.
      RESULTS: Intraoperatively, an L5-S1 anastomotic nerve root on the left side was
      identified. CONCLUSIONS: This case emphasizes the need to consider the presence
      of lumbosacral nerve root anomalies in cases in which neurologic findings exceed
      what would be anticipated. Preoperative identification of these anomalies allows
      for their existence to be considered in the surgical plan.

PMID- 16946647
TI  - Cervical dural arteriovenous fistula presenting with brainstem dysfunction: case
      report and review.
AB  - STUDY DESIGN: We present a rare case of cervical dural arteriovenous fistula (C
      DAVF) presenting with brainstem dysfunction. We discuss the details of the case
      and review previous articles on C-DAVF. OBJECTIVES: Our case study illustrates
      the relation between uncommon neurologic findings and altered hemodynamics
      resulting from the anatomic features of the neural pathway. Based on a review of
      31 cases of C-DAVFs published since 1990 (30 patients, including our own), we
      sought to determine which surgical treatment for C-DAVF, endovascular surgery, or
      direct interruption of the draining vein, is more effective. SUMMARY OF THE
      BACKGROUND DATA: A combination of endovascular techniques and direct interruption
      procedures was successful in curing the C-DAVF in our patient. The selection
      between endovascular surgery and surgical interruption in the treatment of C-DAVF
      is controversial. METHODS: We sought to identify the characteristics and surgical
      methods most closely associated with complete cure for C-DAVF. RESULTS.:
      According to the reports on 31 cases of C-DAVF treated surgically (including our
      own), 20 DAVFs were managed by open surgery with interruption, 8 were treated by
      endovascular surgery, and 3 underwent a combined open and endovascular approach.
      Twenty-one patients showed symptomatic improvement or stabilization without
      additional treatment during the postsurgical course. Surgical revisions were
      performed in 3 patients (10.0%) (including the present case), all of whom
      initially underwent endovascular surgery. None of the cases treated by surgical
      interruption of the draining vein showed signs of recurrence. CONCLUSIONS:
      Surgical interruption of the draining vein is more effective than endovascular
      surgery in bringing about an absolute cure for C-DAVF. In exceptional cases,
      however, endovascular surgery is the preferred treatment. This is particularly so
      for elderly or medically compromised cases with contraindications against general
      anesthesia, as well as for moribund cases which, like our own case, present with
      rapidly deteriorating neurologic status on admission.

PMID- 16946649
TI  - In vivo evaluation of plasmid DNA encoding OP-1 protein for spine fusion.
AB  - STUDY DESIGN: A posterolateral lumbar interbody arthrodesis animal model was
      selected to evaluate the percutaneous delivery of OP-1 plasmid DNA. OBJECTIVE.:
      To evaluate the feasibility of achieving ectopic bone formation using nonviral
      gene delivery with a minimally invasive technique, by coinjecting plasmid DNA
      encoding OP-1 with collagen into the paraspinal muscle. SUMMARY OF BACKGROUND
      DATA: Osteoinductive proteins show great promise for achieving spine fusion but
      suffer from poor bioavailability. Viral gene transfer can produce therapeutic and
      sustained levels of osteoinductive proteins to achieve osteogenesis in a variety
      of animal models. Toxicity and immunogenicity concerns, however, limit the appeal
      of viral gene therapy for spine fusion. METHODS: Single-level posterior lumbar
      arthrodesis was attempted at L5-L6 in 64 adult Sprague-Dawley rats bilaterally.
      OP-1 plasmid DNA was injected with and without collagen carrier above the L5
      transverse process either percutaneously or after open surgery. Bone formation
      was evaluated at 2 and 4 weeks by manual palpation, posterolateral radiographs,
      and nondecalcified histology. Control animals received the rhOP-1 protein.
      RESULTS: Bone formation was detected histologically after the percutaneous and
      open surgical delivery of 25 microg or 500 microg, respectively, of OP-1 plasmid
      DNA (pVR1055-OP1) and collagen (bone formation = 75% and 50%), but was weaker
      than that observed after injection of 30 microg of rhOP-1 protein and collagen
      (bone formation = 100%). Single-level spine fusion was only achieved in groups
      receiving percutaneous OP-1 protein and collagen (30 microg protein, fusion rate
      = 100%) or high concentrations of OP-1 protein alone (40 microg protein, 100%),
      as confirmed through manual palpation, histology, and radiography. CONCLUSIONS.:
      These data confirm that OP-1 plasmid DNA can successfully generate bone formation
      in vivo.

PMID- 16946650
TI  - Comparative effects of bone morphogenetic proteins and sox9 overexpression on
      extracellular matrix metabolism of bovine nucleus pulposus cells.
AB  - STUDY DESIGN: An in vitro biologic study of the effects of adenovirus expressing
      bone morphogenetic proteins (BMPs) and adenovirus expressing Sox9 on
      extracellular matrix metabolism by bovine nucleus pulposus cells. OBJECTIVE: To
      compare the effects of recombinant adenoviral vectors expressing various BMPs (2,
      3, 4, 5, 7, 8, 10, 11, 12, 13, 14, and 15) and Sox9 on extracellular matrix
      accumulation by bovine nucleus pulposus cells. SUMMARY OF BACKGROUND DATA:
      Nucleus pulposus matrix production may be promoted by transducing the cells with
      genes that permit the sustained expression of growth factors. The choice of the
      particular factors or BMPs to be studied for these applications has been largely
      based on the commercial availability of such products. To our knowledge, this
      study is the first effort to evaluate systematically the relative effectiveness
      of the various members of the BMP family in promoting intervertebral disc matrix
      repair. METHODS: Adult bovine nucleus pulposus cells cultured in monolayer were
      transduced with adenoviruses expressing human BMP-2, 3, 4, 5, 7, 8, 10, 11, 12,
      13, 14, and 15, and adenovirus expressing Sox9. Proteoglycan and collagen
      accumulation, and cell proliferation were measured 6 days after viral
      transduction. As a positive control, cells were cultured without any exogenous
      gene in the presence of recombinant human (rh)BMP-7. RESULTS: Nucleus pulposus
      cells transduced with adenoviruses expressing BMP-2, 3, 4, 5, 7, 8, 10, 13, 15,
      and Sox9 accumulated more proteoglycans than nucleus pulposus cells transduced
      with adenovirus expressing green fluorescent protein (control). It is noteworthy
      that nucleus pulposus cells transduced with adenoviruses expressing BMP-2 and 7
      resulted in essentially as great a stimulation of proteoglycan accumulation as
      nucleus pulposus cells maintained in the presence of rhBMP-7 (adenoviruses
      expressing BMP-2: 104% increase; adenoviruses expressing BMP-7: 162% increase;
      and rhBMP-7: 120% increase). Nucleus pulposus cells transduced with BMP-2, 4, 5,
      7, 8, 10, 14, 15, and Sox9 accumulated significantly more collagen compared to
      nucleus pulposus cells transduced with adenovirus expressing green fluorescent
      protein; adenoviruses expressing BMP-4 and 14 were the most effective (552% and
      661% increase, respectively). Nucleus pulposus cells also proliferated, as
      measured by deoxyribonucleic acid content, when transduced with adenoviruses
      expressing BMP-2 and 8. CONCLUSIONS: To our knowledge, for the first time, we
      have shown the relative effectiveness of 12 different BMPs and Sox9 in
      stimulating proteoglycan and collagen production by nucleus pulposus cells.
      Adenoviruses expressing BMP-2 and 7 were the most effective in stimulating
      proteoglycan accumulation, while adenoviruses expressing BMP-4 and 14 were the
      most effective in stimulating collagen accumulation. To our knowledge, this study
      is the first to compare the relative effectiveness of various BMPs and Sox9 on
      extracellular matrix accumulation by nucleus pulposus cells, and could help to
      develop more efficacious approaches to the treatment of degenerating
      intervertebral discs.

PMID- 16946651
TI  - Healos/recombinant human growth and differentiation factor-5 induces
      posterolateral lumbar fusion in a New Zealand white rabbit model.
AB  - STUDY DESIGN: Posterolateral lumbar spine fusions in New Zealand white rabbits.
      OBJECTIVE: To evaluate the efficacy of recombinant human growth and
      differentiation factor-5 (rhGDF-5) lyophilized to a Healos carrier (cross-linked
      type I collagen with hydroxyapatite coating; DePuy Spine, Inc., Raynham, MA) in
      inducing fusion. SUMMARY OF BACKGROUND DATA: Bone graft substitutes have become
      an area of considerable interest. rhGDF-5 is one such product. Limited lumbar
      preclinical studies have been performed with this product. METHODS: Single-level,
      intertransverse process fusions were performed in 67 rabbits using iliac crest
      autograft (n = 13), Healos alone (n = 13), or 0.5, 1.0, or 1.5 mg/cc rhGDF-5
      lyophilized to Healos (n = 13 per group). At 8 weeks, the rabbits were
      euthanized. Fusion masses were assessed. RESULTS: There were 2 animals (3%) lost
      to complication. Manual palpation revealed fusion rates for autograft of 38%
      (5/13), Healos alone of 0% (0/13), and each of the Healos/rhGDF-5 groups of 100%
      (13/13). Histologic analyses were 95% sensitive and 95% specific for confirming
      fusion. Histologic differences were found among the treatment groups.
      CONCLUSIONS: In this rabbit fusion model, Healos/rhGDF-5 induced fusion in 100%
      of the rabbits studied. This rate was significantly higher than the fusion rate
      induced by autograft (38%). Overall, these results support continued research of
      Healos/rhGDF-5 as a potential bone graft alternative.

PMID- 16946652
TI  - Effect of lumbar interbody cage geometry on construct stability: a cadaveric
      study.
AB  - STUDY DESIGN: Biomechanical study to investigate three-dimensional motion
      behavior of cadaveric spines in various surgical simulations. OBJECTIVES: To
      determine the effect of cage geometry on the construct stability. SUMMARY OF
      BACKGROUND DATA: There is a wide variety of cage/spacer designs available for
      lumbar interbody fusion surgery. These range from circular, tapered, and
      rectangular with and without curvature. However, the effectiveness of cages with
      different designs and materials to stabilize a decompressed intervertebral space
      has not been fully studied. METHODS: Six fresh ligamentous lumbar spine specimens
      (L1-S2) were subjected to pure moments in the six loading directions. The
      resulting spatial orientations of the vertebrae were recorded using Optotrak
      Motion Measurement System. Measurements were made sequentially for intact,
      bilateral spacer placements across L4-L5 using a posterior approach, supplemented
      with pedicle screw-rod system fixation, and after the cyclic loading in flexion
      extension mode. RESULTS: The stability tended to decrease after the bilateral
      cage placement as compared with the intact for all loading cases except flexion.
      In flexion, the angular displacement decreased to 80% of the intact. However,
      there was no significant statistical difference seen in stability between intact
      and after bilateral spacer placement. Following the addition of posterior
      fixation using pedicle screw-rod system, the stability significantly increased in
      all directions. Cyclic loading did not have any significant effect on the
      stability. CONCLUSIONS: Stand-alone cages restore motion to near-intact levels at
      best, and supplement instrumentation is essential for significantly increasing
      the stability of the decompressed segment. The effects of cage geometry and
      Young's modulus of the cage material do not seem to influence the stability, as
      compared with the other cagedesigns, especially after supplemental fixation with
      a posterior system.

PMID- 16946653
TI  - Biomechanical study of anterior cervical corpectomy and step-cut grafting with
      bioabsorbable screws fixation in cadaveric cervical spine model.
AB  - STUDY DESIGN: An in vitro biomechanical study. OBJECTIVE: To determine the
      initial stability of a novel construct in a 1-level cadaveric cervical spine
      model by comparing it with a conventional method. SUMMARY OF BACKGROUND DATA:
      Lots of endeavors have been made to enhance fusion rates and reduce complications
      in the anterior cervical spine procedure. METHODS: There were 12 fresh human
      cadaveric cervical spines (C3-C7) randomly divided into 2 groups: group 1, 1
      level corpectomy of C5 and step-cut grafting with bioabsorbable screw fixation
      (SCAS); and group 2, 1-level corpectomy of C5 and strut grafting with anterior
      plate fixation (SP). For each specimen, the intact underwent a flexibility test
      first, followed by the instrumented construct. Rotational angles of the C4-C6
      segment were measured to study the immediate stability of anterior cervical
      corpectomy and SCAS, compared with the intact and anterior cervical corpectomy
      and SP. RESULTS: Both anterior cervical corpectomy with SCAS and with SP
      significantly (P < 0.01) decreased the motions of C4-C6 in all 6 degrees of
      freedom after instrumentation. Compared with anterior cervical corpectomy and SP,
      anterior cervical corpectomy and SCAS had higher stability (P < 0.05) in
      extension, and comparable stability (P > 0.05) in flexion and axial rotation, but
      lower stability (P <or= 0.05) in lateral bending. CONCLUSION: Anterior cervical
      corpectomy and SCAS, a novel method of anterior cervical spine decompression and
      reconstruction, was introduced. The in vitro biomechanical study showed that
      anterior cervical corpectomy and SCAS had sufficient immediate stability except
      for the lateral bending, compared with anterior cervical corpectomy and SP, in a
      1-level cadaveric cervical spine model. However, an animal experimental in vivo
      evaluation of anterior cervical corpectomy and SCAS still has to be performed.

PMID- 16946654
TI  - A biomechanical analysis of sublaminar and subtransverse process fixation using
      metal wires and polyethylene cables.
AB  - STUDY DESIGN: An in vitro biomechanical calf thoracic spine study. OBJECTIVE: To
      evaluate the biomechanical stability of sublaminar and subtransverse process
      fixation using stainless steel wires and ultra-high molecular weight polyethylene
      (UHMWPE) cables. SUMMARY OF BACKGROUND DATA: It is commonly held that transverse
      process fixation provides less stability than sublaminar fixation. To our
      knowledge, this is the first biomechanical study to compare the stability
      afforded by sublaminar fixation and subtransverse process fixation using metal
      wire and UHMWPE cable before and after cyclic loading. METHODS: There were 6
      fresh-frozen calf thoracic spines (T4-T9) used to determine the sublaminar
      fixation stiffness and subtransverse process fixation stiffness in each group.
      Double strands of 18-gauge stainless steel wire, 3 and 5 mm-width UHMWPE cable
      (Nesplon; Alfresa, Inc., Osaka, Japan) were applied to each spine. Cyclic pure
      flexion-extension moment loading (2 Nm, 0.5 Hz, 5000 cycles) was applied after
      the initial stability was analyzed by measuring the range of motion. Statistical
      analyses were used to delineate differences between the various experimental
      groups. RESULTS: Subtransverse process wiring was more stable than sublaminar
      wiring after cyclic loading in flexion-extension (P < 0.05). There were no
      significant differences between each group in lateral bending and axial rotation
      after cyclic loading. Sublaminar stainless steel wiring was more stable than
      sublaminar 3 and 5-mm cable before and after cyclic loading in axial rotation (P
      < 0.01). Acute subtransverse process fixation using 3-mm cable was less stable
      after cyclic loading in axial rotation (P < 0.05). All other groups did not
      produce statistically significant differences. CONCLUSIONS: Subtransverse process
      fixation provides at least as much stability as sublaminar fixation. A 5-mm
      UHMWPE cable and stainless steel wire result in equivalent sublaminar and
      subtransverse process stability.

PMID- 16946655
TI  - Cobalt chromium sublaminar wires for spinal deformity surgery.
AB  - STUDY DESIGN: Biomechanical analysis and retrospective chart review. OBJECTIVES:
      To determine the mechanical properties of cobalt chromium alloy wires and review
      the clinical application of the wires as sublaminar implants to correct spinal
      deformity. SUMMARY OF BACKGROUND DATA: Sublaminar wires are commonly used as
      anchors in spinal deformity surgery. In stainless steel instrumentation systems,
      single strand wires (Luque wires) may be retightened over time to take advantage
      of stress relaxation while correcting spinal deformity. Because of the mechanical
      properties of titanium, solid titanium wires are not used as sublaminar wires.
      Cobalt chromium alloy is a titanium compatible alloy that can be twisted in a
      similar fashion to stainless steel sublaminar wires. METHODS: Comparative tensile
      tests were performed using cobalt chromium alloy wires and Luque stainless steel
      wires. In addition, 22 consecutive posterior spinal fusions for idiopathic
      scoliosis were performed using cobalt chromium alloy wires as sublaminar
      implants. RESULTS: Yield and ultimate tensile loads for the cobalt chromium alloy
      wires are on average 66% (P < 0.001) and 60% (P < 0.001) higher, respectively,
      than those for the steel wires. Mean preoperative thoracic curve for patients
      with idiopathic scoliosis was 56 degrees +/- 15 degrees , which corrected to 19
      degrees +/- 11 degrees (67% correction, P < 0.001) when cobalt chromium alloy
      wires were used as sublaminar implants. Mean preoperative lumbar curve was 52
      degrees +/- 14 degrees , which corrected to 17 degrees +/- 8 degrees (68%
      correction, P < 0.001). There were no instrumentation failures, neurologic
      complications, or infections. CONCLUSIONS: The advantages of cobalt chromium
      alloy wire over steel wire include greater tensile strength and titanium
      compatibility. Cobalt chromium alloy solid wires may be used as sublaminar
      implants with titanium spinal instrumentation with excellent clinical results.

PMID- 16946656
TI  - Balloon kyphoplasty for symptomatic vertebral body compression fractures results
      in rapid, significant, and sustained improvements in back pain, function, and
      quality of life for elderly patients.
AB  - STUDY DESIGN: Prospective, single-arm interventional cohort. OBJECTIVE: To
      evaluate the safety and effectiveness of balloon kyphoplasty to treat symptomatic
      vertebral body compression fractures (VCFs). SUMMARY OF BACKGROUND DATA: VCFs
      treated nonoperatively can diminish function and quality of life, and lead to
      chronic health effects. The short-term safety and effectiveness of balloon
      kyphoplasty for symptomatic VCFs are well-documented, but long-term follow-up is
      needed. METHODS: A total of 155 elderly patients with symptomatic VCFs were
      enrolled in a prospective, multicenter treatment study of balloon kyphoplasty at
      19 geographically diverse US centers. Outcomes included back pain severity,
      bedrest, and limited activities because of back pain, back disability score, and
      SF-36 Medical Outcomes Survey, at 7 days (visual analog scale only), and 1, 3,
      12, and 24 months after treatment. RESULTS: Patients reported severe back pain
      (15/20 on visual analog scale) interfering with daily activities 90% of days per
      month before kyphoplasty. Physical functioning and quality of life were also
      markedly impaired. Statistically significant (P < 0.001) improvements occurred in
      all pain, functional, and mental health outcomes at the first follow-up after
      treatment and were maintained for 24 months. CONCLUSIONS: Elderly patients with
      symptomatic VCFs had rapid, significant, and sustained improvements in back pain,
      back function, and quality of life following balloon kyphoplasty.

PMID- 16946657
TI  - Effects of perioperatively administered bupivacaine and bupivacaine
      methylprednisolone on pain after lumbar discectomy.
AB  - STUDY DESIGN: A prospective, randomized, controlled trial that compared the
      efficacy of different protocols of local tissue infiltration with bupivacaine or
      bupivacaine-methylprednisolone at the surgical site for pain relief after lumbar
      discectomy. OBJECTIVE: To determine the efficacy of preemptive wound infiltration
      with bupivacaine and bupivacaine-methylprednisolone after lumbar discectomy.
      SUMMARY OF BACKGROUND DATA: Patients usually have significant pain after lumbar
      discectomy. Wound infiltration with bupivacaine or bupivacaine-methylprednisolone
      is one method to address this. METHODS: Seventy-five patients were randomly
      allocated to 5 equal groups as follows: Group I (n = 15) had the musculus
      multifidi near the operated level infiltrated with 30 mL 0.25% bupivacaine and 40
      mg methylprednisolone just before wound closure; Group II (n = 15) had the same
      region infiltrated with 30 mL 0.25% bupivacaine alone before closure; Group III
      (n = 15) had this region infiltrated with 30 mL 0.25% bupivacaine and 40 mg
      methylprednisolone before the incision was made; in Group IV (n = 15), this
      region infiltrated with 30 mL 0.25% bupivacaine alone before incision; and Group
      C (controls, n = 15) had this region infiltrated with 30 mL 0.9% NaCl just before
      wound closure. Demographics, vital signs, postoperative pain scores, and morphine
      usage were recorded. RESULTS: All 4 groups treated with bupivacaine or
      bupivacaine-methylprednisolone (by preemptive or preclosure wound infiltration)
      showed significantly better results than the control group for most parameters.
      The treated groups had lower parenteral opioid requirements after surgery, lower
      incidences of nausea, and shorter hospital stays. Further, the data indicate
      that, compared with infiltration of these drugs at wound closure, preemptive
      injection of bupivacaine or bupivacaine-methylprednisolone into muscle near the
      operative site provides more effective analgesia after lumbar discectomy.
      CONCLUSION: In addition, our data suggest that preemptive infiltration of the
      wound site with bupivacaine alone provides similar pain control to preemptive
      infiltration of the wound site with bupivacaine and methylprednisolone combined.

PMID- 16946658
TI  - Impact of intraoperative normovolemic hemodilution on transfusion requirements
      for 68 patients undergoing lumbar laminectomies with instrumented posterolateral
      fusion.
AB  - STUDY DESIGN: To determine whether the normovolemic hemodilution (NH) technique
      would limit postoperative homologous blood transfusion requirements in 68
      patients having multilevel lumbar laminectomies (3-6 levels) with predominant 1-
      or 2-level instrumented fusions. OBJECTIVE: In this setting, to define
      postoperative homologous blood transfusion requirements using NH. SUMMARY OF
      BACKGROUND DATA: NH limits postoperative homologous blood transfusion
      requirements following various types of surgical procedures including those on
      the spine. METHODS: NH was used in an attempt to limit postoperative homologous
      transfusion requirements in 68 patients undergoing lumbar surgery. NH involves
      the removal of 1 to 2 U of blood replaced with crystalloid (2-4 mL per milliliter
      of blood harvested). Multiple variables contributing to homologous transfusion
      requirements were analyzed. RESULTS: Using NH, no homologous blood transfusions
      were required in 52 patients with a mean preoperative hematocrit of 41.3
      undergoing average 3.7 level laminectomies with 1.5 level fusions. However, 16
      patients with an average preoperative hematocrit of 38.5 undergoing average 4.3
      level laminectomies with 1.6 level fusions required transfusion of 31 U of
      homologous blood after surgery. CONCLUSIONS: Using NH, 16 (23.5%) patients
      required 31 postoperative homologous blood transfusions. By contrast, the
      remaining 52 patients with similar procedures were able to avoid the use of
      homologous transfusion.

PMID- 16946660
TI  - Comparison of the lowest instrumented, stable, and lower end vertebrae in "single
      overhang" thoracic adolescent idiopathic scoliosis: anterior versus posterior
      spinal fusion.
AB  - STUDY DESIGN: A retrospective multicenter study. OBJECTIVE: To investigate the
      relationship between the lowest instrumented, stable, and lower end vertebrae in
      patients with "single overhang" thoracic (main thoracic) curves treated with
      anterior or posterior spinal fusion. SUMMARY OF BACKGROUND DATA: Previous studies
      have shown "saving" fusion levels with anterior spinal fusion, as opposed to
      posterior spinal fusion; however, to our knowledge, none of these studies
      evaluated the relative position to the lower end vertebra to compare study groups
      accurately. For clarification, "single overhang" includes Lenke 1A and 1B curves.
      For these thoracic curves, the lumbar curve does not cross the midline. MATERIALS
      AND METHODS: A retrospective multicenter study of adolescent idiopathic scoliosis
      was performed to identify specifically patients with "single overhang" thoracic
      (Lenke 1A and 1B) curves with more than a 2-year follow-up. To analyze relative
      fusion levels, the differences were computed as follows: (1) the difference
      between the vertebra position for the stable vertebra of the main thoracic (MT)
      curve and the lowest instrumented vertebra, as noted on postoperative
      radiographs, or [equation: see text] (2) the difference between the vertebra
      position for the lower end vertebra of the main thoracic (MT) curve and the
      lowest instrumented vertebra, as noted on postoperative radiographs, or
      [equation: see text]. RESULTS: A total of 298 "single overhang" thoracic curves
      (148 Lenke 1A, 150 Lenke 1B) were identified, of which 293 had either an anterior
      spinal fusion or posterior spinal fusion; 5 patients underwent a combined
      anterior-posterior spinal fusion. Anterior spinal fusion was performed in 70
      patients (23.9%) and posterior spinal fusion in 223 (76.1%). While comparing the
      lowest instrumented vertebra to the stable vertebra with anterior spinal fusion,
      the lowest instrumented vertebra was identified either at the level of the stable
      vertebra or above in 97% of 1A/B curves (P < 0.001). Using posterior spinal
      fusion techniques, the lowest instrumented vertebra was identified either at the
      stable vertebra or above in 65% of the 1A/B curves (P < 0.05). CONCLUSIONS: These
      data confirm that anterior spinal fusion techniques result in a mean shorter
      fusion of 1.5 vertebral segments/patient when compared to posterior spinal fusion
      techniques with respect to the position of the lowest instrumented and stable
      vertebrae for "single overhang" thoracic (Lenke 1A/B) curves. However, because
      this is a retrospective multicenter study over 10 years, it represents various
      posterior spinal fusion techniques that do not include all pedicle screw
      constructs.

PMID- 16946661
TI  - The mobility capabilities of persons with adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: An analysis of differences among healthy elementary school children
      and those with adolescent idiopathic scoliosis (AIS), and between groups of
      individuals with AIS with different Cobb angles. OBJECTIVES: To research the
      differences in dynamic balance among adolescents with a variety of postural
      statuses and verify the sensitivity value of the Cobb angle. SUMMARY OF
      BACKGROUND DATA: Assuming the biomechanical and functional particularities of the
      children with AIS, there is a need for an earlier diagnosis. METHODS: The
      participants' balance (left and right step test) was estimated using
      electromyography and the reaction of base power on the platform. RESULTS:
      Discriminant analysis confirmed a significant difference between the participants
      with AIS and healthy persons on the left step test. The values of the lumbal
      erector muscles, right gluteus, and side-to-side reaction of the force platform
      are more pronounced than the other variables. There is no significant difference
      among the participants with various Cobb angles. CONCLUSIONS: The dynamic balance
      tests contribute to the AIS screening process. The pathologic form of AIS and
      lateralization highly affect dynamic balance. The study confirmed the
      neurophysicians' claims of the neuroplasticity of the central nervous system. In
      addition, the research illustrated the compensational functioning of mobility,
      especially when there is a lack of normal mobility forms, and there are weak
      postural control mechanisms and proprioception. There was no proof of the value
      of the Cobb angle as a clinical method and a measurement of the functional
      capabilities of the participants in the screening process.

PMID- 16946662
TI  - Dynamic magnetic resonance imaging in assessing lung volumes, chest wall, and
      diaphragm motions in adolescent idiopathic scoliosis versus normal controls.
AB  - STUDY DESIGN: Dynamic breath-hold (BH)- magnetic resonance (MR) imaging was used
      to evaluate lung function in adolescent idiopathic scoliosis (AIS). OBJECTIVES:
      Changes in lung volume, chest wall, and diaphragmatic motions were evaluated in
      AIS patients and compared with normal controls. SUMMARY OF BACKGROUND DATA:
      Little is known about whether pulmonary function impairment in AIS is related to
      restriction of lung volume, poor chest wall expansibility, or impaired
      diaphragmatic motion. This is a study on the underlying pathophysiology of the
      abnormal pulmonary function in AIS using the ultrafast BH-MR imaging technique.
      METHODS: Forty-two patients with moderate to severe right thoracic scoliosis
      (Cobb angle, 40 degrees -98 degrees), 22 patients with mild right thoracic
      scoliosis (Cobb angle 10 degrees -30 degrees), and 12 healthy subjects (age
      ranged, 11-18 years; all girls) were recruited for the following assessments: 1)
      inspiratory, expiratory, and change in lung volume; 2) change in anteroposterior
      (AP) and transverse (TS) diameter of the chest wall at two levels: carina and
      apical vertebra level; and 3) change in diaphragmatic heights. RESULTS:
      Inspiratory, expiratory lung volume and diaphragmatic heights were significantly
      reduced in the severe scoliosis group (P < 0.05), but the change in lung volume
      was not affected. There was no significant difference in the change of AP or TS
      diameter of the chest wall as well as diaphragmatic motions among groups.
      CONCLUSION: Impairment in lung function in AIS patients is predominantly due to
      restriction of lung volume.

PMID- 16946663
TI  - Are "structural abnormalities" on magnetic resonance imaging a contraindication
      to the successful conservative treatment of chronic nonspecific low back pain?
AB  - STUDY DESIGN: Prospective study. OBJECTIVE: To examine the association between
      structural abnormalities recorded on magnetic resonance imaging (MRI) and outcome
      after evidence-based conservative treatment in patients with chronic nonspecific
      low back pain (LBP). SUMMARY OF BACKGROUND DATA: In most guidelines for the
      management of LBP, MRI is not recommended unless the diagnostic triage suggests
      serious spinal pathology or nerve root involvement for which surgical treatment
      is foreseen. This is because many structural changes seen on MRI appear to be as
      common in asymptomatic individuals as in people with LBP and are, therefore,
      considered of little value in either explaining the cause of pain or deciding the
      subsequent course of management. However, to our knowledge, no studies have
      assessed whether the presence of such MRI abnormalities influences the outcome of
      the conservative treatment that patients with chronic nonspecific LBP typically
      receive. METHODS: T2-weighted, 4-mm spin-echo MRI sequences of the lumbar spine
      were obtained from 53 patients with chronic nonspecific LBP before a 3-month
      program of exercise therapy. Disc degeneration, disc bulging, high intensity
      zones, and endplate/bone marrow changes were assessed for each lumbar segment.
      Back pain (average and worst) and disability (Roland Morris score) were assessed
      before and after therapy, and 12 months later, and the improvements were examined
      in relation to the presence or absence of baseline MRI "abnormalities." RESULTS:
      Eighty-nine percent of patients had severe disc degeneration (grade 4 or 5), 74%
      had disc bulging, 60% had high intensity zones, and 62% had endplate/bone marrow
      changes in at least 1 lumbar segment. Only 11% patients had none of these changes
      at any level. The MRI abnormalities showed only minimal association with baseline
      symptoms. In multivariate regression analyses, in which age, gender, and baseline
      symptoms were controlled for, only 1 significant association between the MRI
      variables and outcome was observed: the presence of a high intensity zone in any
      vertebral segment was associated with lower average pain at the 12-month follow
      up (standardized beta -0.376, P = 0.006, 16.5% variance accounted for).
      CONCLUSION: In the patient group examined, the presence of common "structural
      abnormalities" on MRI had no significant negative influence on the outcome after
      therapy.

PMID- 16946664
TI  - Relationship between low back pain and lumbar multifidus size at different
      postures.
AB  - STUDY DESIGN: A prospective study of multifidus images. OBJECTIVE.: To compare
      the change of the cross-sectional area (CSA) of multifidus in subjects with and
      without chronic low back pain (LBP) at different postures. SUMMARY OF BACKGROUND
      DATA: Ultrasound imaging was shown to be useful in assessing acute LBP patients
      at rest only. METHODS AND MEASURES: Thirty-five male adults participated,
      including 19 normal and 16 chronic LBP patients. The CSAs of multifidus were
      assessed on ultrasound images acquired on both sides of the L4 and L5 levels with
      the subjects in prone lying, upright standing, and 25 degrees and 45 degrees
      forward stooping. RESULTS: In the control group, the CSA of multifidus increased
      from prone lying to upright standing and then gradually decreased from 25 degrees
      to 45 degrees forward stooping. However, a reverse pattern of the CSA changes was
      identified in patients with chronic LBP. CONCLUSION: Multifidus contracts
      maximally at upright standing in the normal group, while maximum contraction of
      the muscle occurs at 25 degrees forward stooping in the patient group. The role
      of multifidus may be altered in the stabilization of the lumbar spine of chronic
      LBP patients. Assessment of the change in muscle size reacting to different
      postures is found to be helpful.

PMID- 16946665
TI  - Racial variation in treatment preferences and willingness to randomize in the
      Spine Patient Outcomes Research Trial (SPORT).
AB  - STUDY DESIGN: Analysis of baseline data for patients enrolled in Spine Patient
      Outcomes Research Trial (SPORT), a project conducting three randomized and three
      observational cohort studies of surgical and nonoperative treatments for
      intervertebral disc herniation (IDH), spinal stenosis (SpS), and degenerative
      spondylolisthesis (DS). OBJECTIVE: To explore racial variation in treatment
      preferences and willingness to be randomized. SUMMARY OF BACKGROUND DATA:
      Increasing minority participation in research has been a priority at the NIH.
      Prior studies have documented lower rates of participation in research and
      preferences for invasive treatment among African-Americans. METHODS: Patients
      enrolled in SPORT (March 2000 to February 2005) that reported data on their race
      (n = 2,323) were classified as White (87%), Black (8%), or Other (5%). Treatment
      preferences (nonoperative, unsure, surgical), and willingness to be randomized
      were compared among these groups while controlling for baseline differences using
      multivariate logistic regression. RESULTS.: There were numerous significant
      differences in baseline characteristics among the racial groups. Following
      adjustment for these differences, Blacks remained less likely to prefer surgical
      treatment among both IDH (White, 55%; Black, 37%; Other, 55%, P = 0.023) and
      SpS/DS (White, 46%; Black, 30%; Other, 43%; P = 0.017) patients. Higher
      randomization rates among Black IDH patients (46% vs. 30%) were no longer
      significant following adjustment (odds ratio [OR] = 1.45, P = 0.235). Treatment
      preference remained a strong independent predictor of randomization in
      multivariate analyses for both IDH (unsure OR = 3.88, P < 0.001 and surgical OR =
      0.23, P < 0.001) and SpS/DS (unsure OR = 6.93, P < 0.001 and surgical OR = 0.45,
      P < 0.001) patients. CONCLUSIONS: Similar to prior studies, Black participants
      were less likely than Whites or Others to prefer surgical treatment; however,
      they were no less likely to agree to be randomized. Treatment preferences were
      strongly related to both race and willingness to be randomized.

PMID- 16946666
TI  - Evaluation of surgical volume and the early experience with lumbar total disc
      replacement as part of the investigational device exemption study of the Charite
      Artificial Disc.
AB  - STUDY DESIGN: A prospective, randomized, multicenter, Food and Drug
      Administration regulated Investigational Device Exemption (IDE) clinical trial.
      OBJECTIVES: To discern whether there is a correlation between surgical volume and
      clinical outcomes, as well as the complication rate and perioperative data
      points, for lumbar total disc replacement. To examine the early experience for
      lumbar total disc replacement as part of an IDE study. SUMMARY OF BACKGROUND
      DATA: To our knowledge, an analysis of the effect of surgical volume has not been
      performed for any spine surgical procedure. Prior reports of the early experience
      with lumbar total disc replacement consist of retrospective reviews with
      nonspecific indications. METHODS: An analysis was performed of the Food and Drug
      Administration IDE Study of the Charite Artificial Disc (DePuy Spine, Inc.,
      Raynham, MA). Patients enrolled in the control group were omitted from the
      analysis. Up to 5 nonrandomized cases (representing the early experience) were
      performed at each site before beginning the randomized arm of the study. There
      were 3 comparisons performed: nonrandomized cases (71) versus randomized cases
      (205); randomized cases performed by high-enrolling surgeons versus low-enrolling
      surgeons; and randomized cases at high-volume institutions versus low-volume
      institutions. RESULTS: The high-enrolling groups had a significantly lower mean
      hospital stay and operating time compared to the low-enrolling groups (P < 0.05).
      High-enrolling surgeons and institutions showed significantly shorter operating
      times, length of hospital stay, and complication rates. High-enrolling surgeons
      had significantly fewer device failures and cases of neurologic deterioration.
      Mean operating time and hospital stay were significantly lower in the randomized
      group (P < 0.05) compared to the nonrandomized group. Blood loss and approach
      related complications were similar between the 2 groups. Device failure requiring
      removal was 4.2% in the nonrandomized group and 1.5% in the randomized group.
      CONCLUSIONS: Surgeons and institutions with a high volume of lumbar total disc
      replacement cases have a reduction in key perioperative and postoperative
      parameters that provide a clinical and/or economic benefit. Surgeons may expect
      longer hospital stays, higher blood loss, and a higher rate of certain
      complications in their early experience with total disc replacement procedures,
      but there was no effect on clinical outcomes.

PMID- 16946667
TI  - Laryngeal cancer in the United States: changes in demographics, patterns of care,
      and survival.
AB  - BACKGROUND: Survival has decreased among patients with laryngeal cancer during
      the past 2 decades in the United States. During this same period, there has been
      an increase in the nonsurgical treatment of laryngeal cancer. OBJECTIVE: The
      objectives of this study were to identify trends in the demographics, management,
      and outcome of laryngeal cancer in the United States and to analyze factors
      contributing to the decreased survival. STUDY DESIGN: The authors conducted a
      retrospective, longitudinal study of laryngeal cancer cases. METHODS: Review of
      the National Cancer Data Base (NCDB) revealed 158,426 cases of laryngeal squamous
      cell carcinoma (excluding verrucous carcinoma) diagnosed between the years 1985
      and 2001. Analysis of these case records addressed demographics, management, and
      survival for cases grouped according to stage, site, and specific TNM
      classifications. RESULTS: This review of data from the NCDB analysis confirms the
      previously identified trend toward decreasing survival among patients with
      laryngeal cancer from the mid-1980s to mid-1990s. Patterns of initial management
      across this same period indicated an increase in the use of chemoradiation with a
      decrease in the use of surgery despite an increase in the use of endoscopic
      resection. The most notable decline in the 5-year relative survival between the
      1985 to 1990 period and the 1994 to 1996 period occurred among advanced-stage
      glottic cancer, early-stage supraglottic cancers, and supraglottic cancers
      classified as T3N0M0. Initial treatment of T3N0M0 laryngeal cancer (all sites) in
      the 1994 to 1996 period resulted in poor 5-year relative survival for those
      receiving either chemoradiation (59.2%) or irradiation alone (42.7%) when
      compared with that of patients after surgery with irradiation (65.2%) and surgery
      alone (63.3%). In contrast, identical 5-year relative survival (65.6%) rates were
      observed during this same period for the subset of T3N0M0 glottic cancers
      initially treated with either chemoradiation or surgery with irradiation.
      CONCLUSIONS: The decreased survival recorded for patients with laryngeal cancer
      in the mid-1990s may be related to changes in patterns of management. Future
      studies are warranted to further evaluate these associations.

PMID- 16946669
TI  - Proceedings of the Association of Pediatric Retinal Surgeons Meeting, January 27
      30, 2005, Hawks Cay, Florida, USA.

PMID- 16946668
TI  - Presbycusis: a human temporal bone study of individuals with downward sloping
      audiometric patterns of hearing loss and review of the literature.
AB  - OBJECTIVE: The purpose of this retrospective case review was to identify patterns
      of cochlear element degeneration in individuals with presbycusis exhibiting
      downward sloping audiometric patterns of hearing loss and to correlate these
      findings with those reported in the literature to clarify conflicting concepts
      regarding the association between hearing loss and morphologic abnormalities.
      METHODS: Archival human temporal bones from individuals with presbycusis were
      selected on the basis of strict audiometric criteria for downward-sloping
      audiometric thresholds. Twenty-one temporal bones that met these criteria were
      identified and compared with 10 temporal bones from individuals with normal
      hearing. The stria vascularis volumes, spiral ganglion cell populations, inner
      hair cells, and outer hair cells were quantitatively evaluated. The relationship
      between the severity of hearing loss and the degeneration of cochlear elements
      was analyzed using univariate linear regression models. RESULTS: Outer hair cell
      loss and ganglion cell loss was observed in all individuals with presbycusis.
      Inner hair cell loss was observed in 18 of the 21 individuals with presbycusis
      and stria vascularis loss was observed in 10 of the 21 individuals with
      presbycusis. The extent of degeneration of all four of the cochlear elements
      evaluated was highly associated with the severity of hearing loss based on
      audiometric thresholds at 8,000 Hz and the pure-tone average at 500, 1,000, and
      2,000 Hz. The extent of ganglion cell degeneration was associated with the slope
      of the audiogram. CONCLUSIONS: Individuals with downward-sloping audiometric
      patterns of presbycusis exhibit degeneration of the stria vascularis, spiral
      ganglion cells, inner hair cells, and outer hair cells that is associated with
      the severity of hearing loss. This association has not been previously reported
      in studies that did not use quantitative methodologies for evaluating the
      cochlear elements and strict audiometric criteria for selecting cases.

PMID- 16946670
TI  - Zone I retinopathy of prematurity: clinical characteristics and treatment
      outcomes.
AB  - PURPOSE: To study the clinical characteristics and treatment outcomes after laser
      and surgical treatment in a series of infants with zone I retinopathy of
      prematurity (ROP). METHODS: Preterm infants less than 1,500 g at birth diagnosed
      with zone I ROP were studied. Fifty-seven consecutive eyes in 29 infants with
      zone I ROP were treated with indirect diode laser. Within zone I, two anatomic
      subgroups (anterior and posterior) were defined. Additionally, 27 eyes (15
      patients) with retinal detachment secondary to zone I ROP were surgically
      treated. Structural outcomes were evaluated 3 months after surgery. RESULTS:
      Atypical morphologic characteristics were observed. Thirty-one out of 48 eyes
      (64.6%) with anterior zone I ROP and none of the 9 eyes with posterior zone I ROP
      had a favorable outcome (P < 0.001) after photocoagulation. In the surgery group,
      14 out of 19 (74%) eyes with stage 4 and 1 out of 8 (13%) eyes with stage 5 had
      favorable outcomes. CONCLUSIONS: Atypical clinical features can be observed in
      zone I ROP. A posterior localization of the disease carries a worse prognosis
      after laser photocoagulation. Surgical intervention can effectively reattach the
      retina in a significant number of zone I ROP-related retinal detachments.

PMID- 16946671
TI  - Laser treatment for retinopathy of prematurity: evolution in treatment technique
      over 15 years.
AB  - PURPOSE: To assess the number of laser burns applied to the peripheral retina to
      treat retinopathy of prematurity (ROP) in a recent population of patients and to
      compare that number with historical data. METHODS: The authors performed a
      retrospective chart review of all patients treated for ROP within a single
      practice from 2002-2004. There were 183 eyes from 93 patients. Sufficient data
      for analysis were available on 112 eyes from 57 patients. Data from these
      patients were compared to those of patients reported upon in 1991. RESULTS: The
      average number of laser burns applied to the 112 eyes was 2163. Eyes with zone 1
      disease had an average of 3077 spots and those with zone 2 disease had an average
      of 2072 spots. Greater than three months follow-up was available on 42 eyes from
      21 patients. Of those eyes, 90% had complete regression of ROP. In an initial
      report of laser treatment for ROP by several of the same authors in 1991, the
      average number of laser burns applied for treatment of ROP was 816. There was a
      265% increase in the average number of laser applications from the early study to
      the present. CONCLUSION: The data indicate that there has been a trend towards
      more confluent laser treatment to the avascular zone in ROP.

PMID- 16946672
TI  - Rethinking STOP-ROP: is it worthwhile trying to modulate excessive VEGF levels in
      prethreshold ROP eyes by systemic intervention? A review of the role of oxygen,
      light adaptation state, and anemia in prethreshold ROP.
AB  - PURPOSE: To review systemic modifiable factors that might downregulate pathologic
      levels of vascular endothelial growth factor (VEGF) in prethreshold retinopathy
      of prematurity (ROP), and thereby reduce the risk of blindness in affected
      infants. METHODS: Review of the author's clinical experience as compared to the
      STOP-ROP study, and discussion and literature review of the potential effects of
      oxygen supplementation, light adaptation state, and correction of severe anemia
      on the course of prethreshold retinopathy of prematurity (ROP). RESULTS: Moderate
      oxygen supplementation, combined with light adaptation to reduce retinal oxygen
      consumption and correction of severe anemia, were associated, in the author's
      experience, with improvement in the clinical course of prethreshold ROP.
      Withdrawal of these measures was often associated with deterioration of ROP.
      CONCLUSION: Systemic measures can be taken that may reduce the risk of blindness
      in infants with prethreshold ROP. For those infants who require laser treatment
      for threshold ROP, prior efforts to moderate excessive levels of VEGF may improve
      the chances of a successful surgical result, by slowing the momentum of the
      disease.

PMID- 16946674
TI  - Fibrovascular organization in the vitreous following laser for ROP: implications
      for prognosis.
AB  - PURPOSE: To study associations between surgical outcome and mean postmenstrual
      age (PMA) when fibrovascular organization is detected between vascular and
      avascular retina following laser for acute retinopathy of prematurity (ROP).
      METHODS: PMA at the time of detection of fibrovascular organization was
      determined in infants who had laser treatment for stage 3 ROP. Retinal features
      abstracted from examination sheets included zone, stage, and clock hours of
      fibrovascular organization, PMA at the times of first surgery and diagnosis of
      fibrovascular organization, and outcomes (retinal attachment after one surgery
      and retinal attachment at follow-up). Statistical analyses were performed to
      compare categorical data (Mann-Whitney U test, t-test, Fisher exact test) and
      determine correlations (Spearman rank test). RESULTS: Fibrovascular organization
      was diagnosed in 38/39 eyes that required surgery and 19/41 eyes that did not. In
      surgical eyes, older PMA at the time of detection of fibrovascular organization,
      zone II ROP, and stage 4 (versus stage 5) ROP were each associated with
      successful reattachment of the retina after one surgery and at the end of follow
      up. PMA at diagnosis of fibrovascular organization was associated with zone, but
      not stage, of ROP when surgical intervention was performed. CONCLUSION:
      Fibrovascular organization between the vascular and avascular retina is important
      because it is associated with the development of retinal detachment after laser
      for acute ROP. Further study is required to determine if improved detection of
      fibrovascular organization in eyes of infants of early PMA will improve surgical
      outcomes for retinal detachment.

PMID- 16946675
TI  - Tent-shaped retinal detachments in retinopathy of prematurity.
AB  - BACKGROUND: Most retinal detachments associated with retinopathy of prematurity
      (ROP) are radial, segmental, or circumferential with cicatricial extraretinal
      fibrovascular proliferation (EFP) at the apex of the detachment. This report
      describes peculiar tent-shaped retinal detachments that developed among eyes with
      ROP. METHODS: An observational case series consisting of 9 patients and 13 eyes
      with tent-shaped retinal detachments. Their morphology, clinical baseline,
      surgical course, and final retinal status were extracted from medical records.
      RESULTS: Eight had simple tent-shaped retinal detachments, three had a double
      tent-shaped retinal detachment, one had a chevron-based retinal detachment, and
      one had a star-shaped retinal detachment. Each case had a disk based stalk that
      extended to the apex of the traction retinal detachment and continued anteriorly;
      12 stalks inserted in the retrolental space and 1 terminated in the mid vitreous.
      Six eyes were stage 4A, two eyes were stage 4B, and five eyes were stage 5.
      Vitrectomy surgery was performed on 11 eyes. Surgery resulted in retinal
      attachment in nine eyes, and two retinas remained detached. CONCLUSION: Tent
      shaped retinal detachments are seen in patients with ROP. A stalk should be
      sought in evaluation of these eyes. Vitreous surgery focused on relieving this
      traction is often successful.

PMID- 16946676
TI  - Posterior hyaloid contracture in pediatric vitreoretinopathies.
AB  - BACKGROUND: Retinal detachment in pediatric vasoproliferative disorders such as
      retinopathy of prematurity (ROP) and familial exudative vitreoretinopathy (FEVR)
      have an exudative and tractional component. Younger eyes have an especially
      adherent posterior hyaloid. Contraction of the posterior hyaloid interface may
      lead to tractional retinal detachment. METHODS: Retrospective chart review of six
      eyes (four ROP, two FEVR) with diffuse contraction of the posterior hyaloid
      resulting in retinal detachment. Fundus photographs and optical coherence
      tomography findings (one eye) are presented. RESULTS: Diffuse proliferation along
      the posterior hyaloid required extensive lamellar dissection at times aided by
      autologous plasmin enzyme. A diffuse, taut posterior hyaloid resulted in marked
      tractional component to retinal detachment. CONCLUSIONS: Recognition of hyaloid
      contracture will aid in the proper diagnosis and surgical planning and repair of
      eyes with pediatric vasoproliferative disorders.

PMID- 16946677
TI  - The Photographic Screening for Retinopathy of Prematurity Study (Photo-ROP):
      study design and baseline characteristics of enrolled patients.
AB  - OBJECTIVE: The Photographic Screening for Retinopathy of Prematurity Study (Photo
      ROP) sought to evaluate the utility of digital wide-angle photographic fundus
      screening for retinopathy of prematurity (ROP) as compared to bedside indirect
      ophthalmoscopy. This article describes the study design and presents baseline
      characteristics of the subjects. DESIGN: Prospective, multicenter, masked,
      Internet-based clinical trial. PARTICIPANTS: Premature infants <31 weeks
      postmenstrual age at birth and <1000 g birthweight. INTERVENTIONS: Examinations
      began at 31 weeks postmenstrual age or 4 weeks postnatal age, whichever was
      later. Both eyes of all infants were imaged with a panoramic fundus imaging
      system followed by indirect ophthalmoscopic fundus examination. Images were
      transmitted via Internet to the Reading Center for interpretation by masked
      graders. Clinical interpretations based on indirect ophthalmoscopy were recorded
      for comparison with the Reading Center determinations. Examinations were
      performed weekly for 10 weeks or until an infant was discharged from the
      hospital. MAIN OUTCOME MEASURE: Sensitivity, specificity, and positive and
      negative predictive values of Reading Center image interpretations were compared
      to clinical impressions based on bedside indirect ophthalmoscopy. RESULTS:
      Enrollment began in February 2001 and was completed in February 2002. The target
      number of infants was 50, and 62 were enrolled. Of those enrolled, 51 infants
      (102 eyes) were considered eligible, and are the subject of this article. Mean
      postmenstrual age (+/- SD) at time of delivery was 26.80 +/- 1.73 weeks (median =
      26.86 weeks, interquartile range [IQR] = 2.43 weeks). Mean postmenstrual age at
      first examination (+/- SD) was 32.19 +/- 2.86 weeks (median = 31.71 weeks, IQR =
      2.29 weeks). Mean birthweight (+/- SD) was 830.51 +/- 219.57 g (median = 817 g,
      IQR = 225 g). Female infants comprised 49.02% of the patients. Race distribution
      was as follows: white 45.10%, African or black 39.22%, Hispanic 3.92%, Asian
      9.80%, and other races 1.96%. Mean follow-up (+/- SD) was 5.73 +/- 3.22 weeks
      (median = 6 weeks, IQR = 5, range = [1, 15]). CONCLUSIONS: The Photo-ROP Study
      Cooperative Group successfully recruited and enrolled at-risk premature infants
      into a longitudinal, prospective clinical trial comparing two different
      diagnostic approaches. Technology employed in this study is comparable to that
      currently available. Design issues for this trial included establishing the
      information technology infrastructure for an ROP study based on digital imaging,
      defining the study endpoints, estimating event rates, defining a standardized
      imaging protocol, and defining standards for interpretation of image quality and
      clinical findings.

PMID- 16946678
TI  - 25-Gauge pars plicata vitrectomy for stage 4 and 5 retinopathy of prematurity.
AB  - PURPOSE: To describe the authors' technique and initial experience using the 25
      gauge vitrectomy system for stage 4 and 5 tractional retinal detachment in
      retinopathy of prematurity (ROP). METHODS: Consecutive patients with stage 4 or 5
      ROP treated with 25-gauge vitrectomy surgery between July 2003 and May 2004 were
      studied retrospectively. Eyes with prior vitrectomy surgery were excluded. A
      modified three-port 25-gauge approach was used in which conjunctival dissection
      and suturing of sclerotomies was necessary. The primary outcome was anatomic
      success defined as retinal reattachment. Secondary outcomes were intra- and
      postoperative complications. RESULTS: Fifteen eyes in 12 infants were identified
      that had 25-gauge vitrectomy for stage 4 or 5 ROP: 11/15 (73%) had stage 4A; 2/15
      (13%), stage 4B; and 2/15 (13%), stage 5. All 15/15 (100%) were referred with
      incomplete anterior laser ablation of threshold ROP. Six of 15 (40%) required
      lensectomy at the time of initial pars plicata vitrectomy. Seven of 15 (47%)
      required more than one retinal surgery for persistent retinal detachment and/or
      vitreous hemorrhage. Eleven of 15 (73%) eyes had documented retinal reattachment
      after one or more surgeries at the last follow-up. Complications included
      vitreous hemorrhage (2) and postoperative cataract (1). CONCLUSIONS: Twenty-five
      gauge vitrectomy is a safe and effective treatment approach for tractional
      retinal detachments in stage 4 and 5 ROP. Complications may be comparable to
      vitrectomies performed with two-port 20-gauge vitrectomy. Modifications of the 25
      gauge vitrectomy system included conjunctival dissection and suturing of
      conjunctiva and sclerotomies at the conclusion of the case.

PMID- 16946679
TI  - Vitreoretinal complications of retinoblastoma treatment.
AB  - PURPOSE: To describe complications of the retina and vitreous occurring in
      children undergoing treatment for retinoblastoma and their clinical management.
      METHODS: Retrospective analysis of Ret-Cam images of 206 patients with
      retinoblastoma treated at one center between 1996 and 2003. Images were studied
      for vitreoretinal features other than tumor persistence or recurrence.
      Specifically, complications such as vitreous, retinal, or choroidal hemorrhage,
      retinal detachment, retinal fold, vascular obstruction, and preretinal or
      subretinal proliferation were sought. RESULTS: Vitreoretinal complications of
      retinoblastoma therapy were identified in 14 patients (6.8%) All had heritable
      bilateral retinoblastoma. Group 5 Reese-Ellsworth disease was present in 50% (n =
      7). All patients had systemic chemotherapy, 50% had external beam radiotherapy,
      and 64% had more than one local treatment method. Of the 14 patients with a
      complication, 4 eyes were enucleated for massive recurrence of tumor, 5 eyes were
      observed, and 5 eyes were treated successfully with vitreoretinal surgery for
      tractional or rhegmatogenous retinal detachment. CONCLUSION: Vitreoretinal
      complications occurred in 6.8% of patients undergoing therapy for retinoblastoma.
      These included retinal tears, rhegmatogenous and tractional retinal detachment,
      subretinal fibrosis, vitreous traction bands, preretinal fibrosis, and pseudo
      vitreous seeding. They were more often seen when systemic chemotherapy was
      combined with external beam radiation, cryotherapy, and local chemotherapy.

PMID- 16946680
TI  - Pars plana vitrectomy in eyes treated for retinoblastoma.
AB  - BACKGROUND: As conservative treatments for retinoblastoma become more prevalent,
      there will be a greater number of ocular complications developing in eyes that
      previously would have been enucleated. Pars plana vitrectomy (PPV) is needed to
      manage some of these complications. METHODS: The authors evaluated three
      consecutive cases of PPV in eyes that were successfully treated for
      retinoblastoma from the Retina Service of the Massachusetts Eye and Ear Infirmary
      (MEEI) performed between 1989 and 2004. A review of the literature to date
      regarding PPV after treatment for retinoblastoma was also performed. RESULTS:
      There was no tumor reactivation in the three cases at MEEI. Vision was maintained
      at light perception in one case, and there was improvement in vision from hand
      motions to 20/80 and 20/400 to 20/160 in two cases. Twelve of the 24 cases
      reviewed in the literature were found to have significant complications of
      recurrent tumor, need for enucleation, and/or systemic metastasis. CONCLUSION:
      PPV is associated with significant risks in eyes previously treated for
      retinoblastoma and should be reserved for monocular patients with no other
      alternative for retaining visual function. Areas that may influence outcome
      include different treatment modalities and length of time of documented tumor
      inactivity before PPV.

PMID- 16946681
TI  - Intraschisis cavity fluid composition in congenital X-linked retinoschisis.
AB  - PURPOSE: To describe the intraschisis cavity protein composition in congenital X
      linked retinoschisis (CXLRS) from two eyes of one child. METHODS: The authors
      present a child with complex, Type 3 CXLRS who underwent bilateral surgical
      repair with autologous plasmin enzyme-assisted lens-sparing vitrectomy. Undiluted
      samples of intraschisis fluid and vitreous fluid from two eyes (one child) were
      obtained and used for protein analysis. RESULTS: The patient underwent successful
      schisis repair with plasmin-assisted lens-sparing vitrectomy and silicone oil.
      Two unique protein bands were identified in the intraschisis cavity sample of
      each eye by gel electrophoresis. The proteins were identified as tenascin-C, an
      extracellular matrix protein involved in wound healing, and cystatin C, a
      ubiquitous cysteine protease inhibitor implicated in inflammation. CONCLUSIONS:
      Tenascin-C has previously been described in its complex relationship with decorin
      and fibronectin in normal wound healing. Tenascin's upregulation in sites of
      inflammation and tenascin's role as an antiadhesive molecule may contribute to
      the pathogenesis of CXLRS. To the authors' knowledge, this is the first
      description of intraschisis cavity fluid.

PMID- 16946682
TI  - Congenital X-linked retinoschisis classification system.
AB  - PURPOSE: To establish a classification system for congenital X-linked
      retinoschisis (CXLRS) using clinical examination and optical coherence tomography
      (OCT). METHODS: Thirty-eight eyes of 19 patients who carried a clinical diagnosis
      of CXLRS were examined with OCT and clinical examination. Eyes were classified
      into one of four types based on a combination of clinical examination and OCT.
      RESULTS: All patients had bilateral OCT scanning performed at an average age of
      8.64 years (range 2.24-17.4 years). Review of OCT scans revealed that 37 of 38
      eyes had foveal schisis (97%) while 31 of 38 (82%) eyes had macular schisis
      deeper than the nerve fiber layer in areas of ophthalmoscopically normal macular
      retina. The authors termed this flat schisis phenomenon lamellar schisis. Thirty
      of 38 (79%) had peripheral bullous schisis cavities present. CONCLUSIONS: OCT
      examinations of patients with CXLRS reveal lamellar schisis in areas of
      ophthalmoscopically normal macular retina in 82% of eyes with the clinical
      diagnosis of CXLRS. Using both clinical examination and OCT, the authors were
      able to identify foveal, lamellar, and peripheral schisis, lamellar schisis only
      identifiable by OCT. These findings allow the authors to propose a classification
      system. The authors hope this classification system will allow a better
      understanding of the natural history of CXLRS disease and allow testing of
      therapeutic options.

PMID- 16946683
TI  - Evaluation of open globe injuries of children in the last 12 years.
AB  - PURPOSE: To determine whether advances in vitreoretinal surgical techniques
      developed over the last decade have translated into improved anatomic and visual
      outcomes. METHODS: Retrospective review of children under the age of 18 who were
      treated for open globe injuries at a children's hospital between January 1990 and
      December 2002. RESULTS: The authors identified 59 open globe injuries seen at a
      single center in the past 12 years. Thirty eyes (51%) required secondary surgery
      after primary closure. Twelve patients underwent pars plana vitrectomy (PPV), and
      all presented with an initial visual acuity of count fingers or worse. Seven
      (58%) had an improvement in vision to 20/200 or better, and 6 (50%) of these
      patients achieved a visual acuity of 20/50 or better. CONCLUSION: Improvements in
      outcome compared to previous studies may signify refinement in technique and an
      increased utility of PPV over the last 10 years.

PMID- 16946684
TI  - Presumed transient reactive astrocytic hyperplasia in immature retina.
AB  - PURPOSE: To describe the appearance and clinical course of small, white,
      endophytic calcific, peripheral lesions in developing retina of premature
      infants. METHODS: Retrospective review of all patients evaluated for retinopathy
      of prematurity (ROP) at a level I neonatal intensive care unit (NICU) in San
      Jose, CA, between January 1, 2003, and December 31, 2004. Patients were examined
      either in the NICU or the affiliated outpatient clinic. Clinical examination
      consisted of dilated fundus examination with 360 degree scleral depression.
      Lesions were identified if they were white, calcific, peripheral, and transient.
      Ancillary testing and examination of family members was performed as indicated.
      RESULTS: A total of 302 unique patients were screened for ROP. Ten lesions were
      identified in seven eyes. Three eyes had two lesions each. All lesions were
      unilateral. The size of the lesions was estimated to range between 500 and 700
      microm. All lesions were located anterior to the vascularized retina, had minimal
      elevation on scleral depression, and demonstrated a predilection for the nasal
      and temporal raphe. Ultrasound findings demonstrated an elevated, hyperechoic
      mass with orbital shadowing. Computed tomography and magnetic resonance imaging
      tests did not demonstrate the lesions. Lesions involute slowly over a period of 6
      months. There were no systemic findings or familial dispositions. CONCLUSION:
      Immature retina in premature infants may predispose to the formation of transient
      reactive astrocytic hyperplasia. Development of mature retinal vascularization
      and spontaneous resolution of lesions should alleviate concerns regarding a more
      malignant diagnosis.

PMID- 16946685
TI  - A randomized comparative study of the effects of oral and topical estrogen
      therapy on the vaginal vascularization and sexual function in hysterectomized
      postmenopausal women.
AB  - OBJECTIVE: To compare the effects of oral and vaginal estrogen therapy (ET) on
      the vaginal blood flow and sexual function in postmenopausal women with previous
      hysterectomy. DESIGN: Fifty-seven women were randomized to receive either oral
      (0.625 mg of conjugated equine estrogens per tablet; n = 27) or topical (0.625 mg
      conjugated equine estrogens per 1 g vaginal cream; n = 30) estrogen administered
      once daily. All women underwent estradiol measurements, urinalysis, pelvic
      examination, introital color Doppler ultrasonographies, and personal interviews
      for sexual symptoms using a validated questionnaire before and 3 months after ET.
      RESULTS: A higher serum level of estradiol was noted in the oral group compared
      with the topical group after 3 months of ET. There were significant increases in
      the number of vaginal vessels and the minimum diastole (P < 0.01), and marked
      decreases of pulsatility index values (P < 0.01) in both groups after ET.
      Regarding the systolic peak, we found a significant decrease only in the topical
      group (P < 0.05). Although the post-ET prevalence of anorgasmia decreased
      significantly in both groups (P < 0.05), changes in other domains, including the
      rates of low libido and coital frequency, were not statistically significant (P >
      0.05). In the topical group, ET improved sexual function on the vaginal dryness
      and dyspareunia domains in a statistically significant manner (P < 0.05), but
      this was not the case in the oral group (P > 0.05). However, the efficacy of oral
      ET for vaginal dryness and dyspareunia reached 80% and 70.6%, respectively. The
      corresponding figures of the topical ET were 79.2% and 75%. CONCLUSIONS: The
      results of our study suggest that ET alone in hysterectomized postmenopausal
      women increases the vaginal blood flow and improves some domains of sexual
      function, but it may not have an impact on diminished sexual desire or activity.
      Compared with systemic therapy, topical vaginal preparations are found to
      correlate with better symptom relief despite the lower serum level of estradiol.

PMID- 16946686
TI  - Hormone therapy and cerebrovascular events: a population-based nested case
      control study.
AB  - OBJECTIVE: The relationship between postmenopausal hormone therapy (HT) and
      cerebrovascular disease has been examined in several epidemiological studies and
      clinical trials with conflicting results. The authors aimed to evaluate the
      association between the use of HT and the incidence of first cerebrovascular
      event. DESIGN: The study cohort comprised 158,031 women 50 to 69 years old
      registered in the U.K. General Practice Research Database between 1991 and 1997.
      The authors conducted a nested case-control analysis using all 920 confirmed
      cases of cerebrovascular events identified during the follow-up (536 of transient
      ischemic attack [TIA]; 259 of ischemic stroke; 125 of hemorrhagic stroke) and
      10,000 controls. RESULTS: The odds ratios of TIA, ischemic stroke, and
      hemorrhagic stroke among women currently using HT were 1.48 (95% CI, 1.17-1.87),
      1.12 (95% CI, 0.78-1.59) and 1.21 (95% CI, 0.76-1.93), respectively, compared to
      never users. The overall risk estimate for having a cerebrovascular event was
      1.34 (95% CI, 1.11-1.61). The risk of TIA was greater (1.96) among women using
      high doses of estrogen (95% CI, 1.34-2.87). CONCLUSION: Overall, a small
      increased risk of stroke associated with HT use of comparable magnitude to the
      one observed in recent clinical trials was found. The increased risk was more
      apparent for TIA than for stroke and was greater at higher doses.

PMID- 16946687
TI  - Mind/body interventions for hot flashes.

PMID- 16946688
TI  - Why does NAMS need a code of ethics?

PMID- 16946689
TI  - Spring cleaning at NAMS: the amended and restated code of regulations.

PMID- 16946691
TI  - Anorexia nervosa and brain tumor in a 14-year-old girl.
AB  - A 14-year-old girl with anorexia nervosa (AN) was found to have an intracranial
      neoplasm. Atypical psychological symptoms prompted further evaluation, including
      electroencephalogram and neuroimaging, which revealed a sellar and suprasellar
      mass. This patient had an eating disorder and a brain tumor, which appear to be
      two unrelated conditions. However, it remains unclear how each affected the
      other. The diagnosis of AN, like all other psychiatric disorders, requires that
      possible medical etiologies and coexisting medical problems be excluded. AN and
      other eating disorders are particularly difficult to diagnose in children and
      adolescents because they often do not present in the manner typical of adults.
      Perceptual and cognitive disturbances associated with AN are difficult to
      evaluate because children and adolescents normally change over time as they
      progress through different stages of development. Therefore, it is particularly
      important to evaluate for the presence of medical conditions when a diagnosis of
      an eating disorder is made in a child or adolescent.

PMID- 16946692
TI  - Presidential stroke: United States presidents and cerebrovascular disease.
AB  - In the United States, more individuals suffer disability from stroke than from
      any other disease, and as many as 11 of the 43 presidents have been affected. In
      this article, the authors review the cases of the United States presidents who
      have had strokes, some of which have occurred while the president was in office,
      having a direct effect on the country.

PMID- 16946693
TI  - Borderline personality disorder and traits in veterans: psychiatric comorbidity,
      healthcare utilization, and quality of life along a continuum of severity.
AB  - OBJECTIVE: To examine the presence of borderline personality disorder (BPD)
      traits in Gulf War veterans, and to assess psychiatric comorbidity, health
      status, healthcare utilization, and quality of life (QOL) along a continuum of
      BPD trait severity. METHOD: BPD and traits were evaluated using the Schedule for
      Non-Adaptive and Adaptive Personality in 576 veterans who were either deployed to
      the Persian Gulf (1990-1991) or were on active duty though not deployed to the
      Gulf. Demographic and military characteristics, personal and family history,
      psychiatric comorbidity, and QOL were also assessed. RESULTS: One or more BPD
      traits were present in 247 subjects (43%), and BPD (>5 traits) was identified in
      15 subjects (3%). The number of traits was significantly associated with age and
      level of education. Lifetime psychiatric comorbidity was significantly associated
      with the number of BPD traits present, and level of functioning, health status,
      healthcare utilization, social functioning, self-injurious tendencies, and
      military/behavioral problems. CONCLUSION: BPD and traits identified in Gulf War
      veterans were associated with significant psychiatric morbidity, poorer QOL, and
      increased utilization of healthcare resources. Early recognition and treatment of
      veterans with BPD symptoms may be warranted to minimize the burden on the
      healthcare system.

PMID- 16946694
TI  - The efficacy and safety of lower doses of aripiprazole for the treatment of
      patients with acute exacerbation of schizophrenia.
AB  - INTRODUCTION: Efficacy and safety of aripiprazole administered at doses lower
      than those previously studied systematically were investigated in patients with
      acute exacerbation of schizophrenia. METHODS: In this double-blind, multicenter
      study, 367 patients requiring inpatient hospitalization for acute relapse of
      schizophrenia were randomized to one of three fixed doses of aripiprazole (2, 5,
      or 10 mg/day) or placebo for 6 weeks. Efficacy and safety parameters were
      assessed weekly. Primary outcome measure was mean change from baseline in
      Positive and Negative Syndrome Scale (PANSS) Total score at endpoint. RESULTS:
      Aripiprazole 10 mg/day produced statistically significantly greater improvements
      from baseline compared with placebo for PANSS Total at endpoint (-11.3 vs -5.3;
      P=.03) and at weeks 2-5. Aripiprazole 5 mg/day did not produce significantly
      greater improvement in PANSS Total compared with placebo at endpoint, although
      significant differences were seen at weeks 3-5. No statistically significant
      improvements compared with placebo were achieved with aripiprazole 2 mg/day at
      any time points. All aripiprazole doses were well tolerated. Aripiprazole was not
      associated with significant extrapyramidal symptoms. CONCLUSION: While
      aripiprazole 5 mg/day warrants further study, the 10 mg/day dose provides
      effective and well-tolerated therapy for management of acute psychosis in
      patients with schizophrenia.

PMID- 16946695
TI  - Healthcare resource utilization in bipolar depression compared with unipolar
      depression: results of a United States population-based study.
AB  - INTRODUCTION: This study examined healthcare utilization in the past year by
      subjects who screened positive for bipolar versus unipolar depression. METHOD: A
      self-administered survey was completed in 2002 by a United States population
      based sample. Respondents were categorized into one of three subgroups: bipolar
      depressed screen positive (BP DEP+, n=394); unipolar depressed screen positive
      (UP DEP+, n=794); and control subjects (n=1,612). RESULTS: For depressive
      symptoms in the past year, BP DEP+ respondents were significantly more likely
      than UP DEP+ respondents to report a healthcare visit to a number of diverse care
      providers. In analyses controlled for demographics and depression severity, the
      differences in psychiatric hospitalization, psychologist/counselor outpatient
      visit, substance abuse/social services visit, and number of emergency room visits
      remained significant between BP DEP+ and UP DEP+ respondents. CONCLUSION:
      Subjects with self-reported bipolar depression sought care more often from a
      number of diverse healthcare resources than subjects with self-reported unipolar
      depression. These findings underscore the morbidity associated with bipolar
      depression.

PMID- 16946696
TI  - Adjunctive treatment for mood stabilization of patients with bipolar I disorder
      treated with lamotrigine.
AB  - OBJECTIVE: To describe the effect of supplemental psychotropic medications,
      specifically anxiolytics with sedative/hypnotics (ASH) combined with lamotrigine
      (LTG) on stabilization of symptoms in patients with bipolar I disorder. METHOD:
      Symptomatic patients participating in two LTG maintenance trials were classified
      post-hoc as those initiating LTG as monotherapy (n=313) or as adjunctive therapy
      (n=814) and further characterized by supplemental add-on therapies received
      during an open-label treatment phase. Patients were considered stabilized if they
      reached a stable dose of LTG monotherapy (100-200 mg/day) and had a Clinical
      Global Impressions-Severity scale score <3 for at least 4 weeks. Stabilization
      rates were compared across initial- and supplemental-treatment groups. RESULTS:
      Patients who initiated and were maintained on LTG monotherapy were stabilized at
      a slightly higher rate compared with those taking LTG adjunctive therapy (55% vs
      48%; P=.080). Stabilization rates were numerically higher for LTG monotherapy
      patients who later received only ASH as supplemental medication compared with LTG
      monotherapy throughout, but this difference was not significant (66% vs 55%;
      P=.271). Stabilization rates were significantly higher for monotherapy patients
      who later received ASH alone versus other psychotropic medications (66% vs 28%;
      P=.001). For patients initiating LTG as adjunctive therapy, adding ASH alone
      resulted in significantly higher stabilization rates than adding another
      psychotropic medication (62% vs 33%; P<.001). CONCLUSION: LTG and adjunctive
      treatment with ASH may be useful in the treatment of acute mood symptoms in
      patients with bipolar I disorder.

PMID- 16946697
TI  - Are we treating schizophrenia effectively? Understanding the primary outcomes of
      the CATIE study.
AB  - The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study for
      schizophrenia was designed to independently evaluate the effectiveness of
      antipsychotic treatment in "real-world" patients. To assess the effectiveness of
      the conventional antipsychotics compared to the atypicals as well as the
      differences among the atypicals, patients were randomized to one of four atypical
      antipsychotics (olanzapine, quetiapine, risperidone, ziprasidone) or a
      representative conventional antipsychotic (perphenazine). Effectiveness was
      defined by time to discontinuation and duration of successful treatment. Time to
      "all-cause" discontinuation reflects both efficacy (ability of a drug to reduce
      symptoms) and safety/tolerability. Phase I revealed discontinuation rates ranging
      from 64% for olanzapine to 82% for quetiapine. Differences among the medications
      may be important in the selection of a drug for a particular patient. Physicians
      should involve the patient in choosing their medication by inquiring about the
      patient's past experience with medications and side effects, educating the
      patient on the risk-benefit ratio, and considering the patient's preference. To
      demonstrate how results of the CATIE study can contribute to the knowledge of
      practicing clinicians, this monograph presents a representative clinical case
      patient and illustrates how the CATIE safety and efficacy data has important
      implications for the patient.

PMID- 16946699
TI  - Structural basis for molecular recognition and presentation of histone H3 by
      WDR5.
AB  - Histone methylation at specific lysine residues brings about various downstream
      events that are mediated by different effector proteins. The WD40 domain of WDR5
      represents a new class of histone methyl-lysine recognition domains that is
      important for recruiting H3K4 methyltransferases to K4-dimethylated histone H3
      tail as well as for global and gene-specific K4 trimethylation. Here we report
      the crystal structures of full-length WDR5, WDR5Delta23 and its complexes with
      unmodified, mono-, di- and trimethylated histone H3K4 peptides. The structures
      reveal that WDR5 is able to bind all of these histone H3 peptides, but only
      H3K4me2 peptide forms extra interactions with WDR5 by use of both water-mediated
      hydrogen bonding and the altered hydrophilicity of the modified lysine 4. We
      propose a mechanism for the involvement of WDR5 in binding and presenting histone
      H3K4 for further methylation as a component of MLL complexes.

PMID- 16946700
TI  - EB virus-encoded RNAs are recognized by RIG-I and activate signaling to induce
      type I IFN.
AB  - Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) are nonpolyadenylated,
      untranslated RNAs, exist most abundantly in latently EBV-infected cells, and are
      expected to show secondary structures with many short stem-loops. Retinoic acid
      inducible gene I (RIG-I) is a cytosolic protein that detects viral double
      stranded RNA (dsRNA) inside the cell and initiates signaling pathways leading to
      the induction of protective cellular genes, including type I interferons (IFNs).
      We investigated whether EBERs were recognized by RIG-I as dsRNA. Transfection of
      RIG-I plasmid induced IFNs and IFN-stimulated genes (ISGs) in EBV-positive
      Burkitt's lymphoma (BL) cells, but not in their EBV-negative counterparts or EBER
      knockout EBV-infected BL cells. Transfection of EBER plasmid or in vitro
      synthesized EBERs induced expression of type I IFNs and ISGs in RIG-I-expressing,
      EBV-negative BL cells, but not in RIG-I-minus counterparts. EBERs activated RIG
      I's substrates, NF-kappaB and IFN regulatory factor 3, which were necessary for
      type I IFN activation. It was also shown that EBERs co-precipitated with RIG-I.
      These results indicate that EBERs are recognized by RIG-I and activate signaling
      to induce type I IFN in EBV-infected cells.

PMID- 16946701
TI  - Synaptic GABAA receptors are directly recruited from their extrasynaptic
      counterparts.
AB  - GABAA receptors mediate the majority of fast synaptic inhibition in the brain.
      The accumulation of these ligand-gated ion channels at synaptic sites is a
      prerequisite for neuronal inhibition, but the molecular mechanisms underlying
      this phenomenon remain obscure. To further understand these processes, we have
      examined the cellular origins of synaptic GABAA receptors. To do so, we have
      created fluorescent GABAA receptors that are capable of binding -bungarotoxin
      (Bgt), facilitating the visualization of receptor endocytosis, exocytosis and
      delivery to synaptic sites. Imaging with Bgt in hippocampal neurons revealed that
      GABAA receptor endocytosis occurred exclusively at extrasynaptic sites,
      consistent with the preferential colocalization of extrasynaptic receptors with
      the AP2 adaptin. Receptor insertion into the plasma membrane was also
      predominantly extrasynaptic, and pulse-chase analysis revealed that these newly
      inserted receptors were then able to access directly synaptic sites. Therefore,
      our results demonstrate that synaptic GABAA receptors are directly recruited from
      their extrasynaptic counterparts. Moreover, they illustrate a dynamic mechanism
      for neurons to modulate GABAA receptor number at inhibitory synapses by
      controlling the stability of extrasynaptic receptors.

PMID- 16946702
TI  - Single-molecule analysis of epidermal growth factor binding on the surface of
      living cells.
AB  - Global cellular responses induced by epidermal growth factor (EGF) receptor
      (EGFR) occur immediately with a less than 1% occupancy among tens of thousands of
      EGFR molecules on single cell surface. Activation of EGFR requires the formation
      of a signaling dimer of EGFR bound with a single ligand to each molecule. How
      sufficient numbers of signaling dimers are formed at such low occupancy rate is
      still not known. Here, we have analyzed the kinetics of EGF binding and the
      formation of the signaling dimer using single-molecule imaging and mathematical
      modeling. A small number of EGFR on the cell surface formed dimeric binding
      sites, which bound EGF two orders of magnitude faster than the monomeric binding
      sites. There was a positive cooperative binding of EGF to the dimeric binding
      sites through a newly discovered kinetic intermediate. These two mechanisms
      facilitate the formation of signaling dimers of EGF/EGFR complexes.

PMID- 16946703
TI  - 3'-end formation signals modulate the association of genes with the nuclear
      periphery as well as mRNP dot formation.
AB  - Multiple studies indicate that mRNA processing defects cause mRNAs to accumulate
      in discrete nuclear foci or dots, in mammalian cells as well as yeast. To
      investigate this phenomenon, we have studied a series of GAL reporter constructs
      integrated into the yeast genome adjacent to an array of TetR-GFP-bound TetO
      sites. mRNA within dots is predominantly post-transcriptional, and dots are
      adjacent to but distinct from their transcription site. These reporter genes also
      localize to the nuclear periphery upon gene induction, like their endogenous GAL
      counterparts. Surprisingly, this peripheral localization persists long after
      transcriptional shutoff, and there is a comparable persistence of the RNA in the
      dots. Moreover, dot disappearance and gene delocalization from the nuclear
      periphery occur with similar kinetics after transcriptional shutoff. Both
      kinetics depend in turn on reporter gene 3'-end formation signals. Our
      experiments indicate that gene association with the nuclear periphery does not
      require ongoing transcription and suggest that the mRNPs within dots may make a
      major contribution to the gene-nuclear periphery tether.

PMID- 16946704
TI  - Dazl can bind to dynein motor complex and may play a role in transport of
      specific mRNAs.
AB  - Male germ cell development includes mitotic and meiotic cell divisions that are
      followed by dramatic morphological changes resulting in the production of
      spermatozoa. Genetic evidence has indicated that the DAZ family genes are
      critical for successful male germ cell development in diverse animals as well as
      humans. In the present study, we investigated the cellular functions of Dazl in
      the mouse male germ cells. We identified a specific interaction of Dazl with the
      dynein light chain, a component of the dynein-dynactin motor complex. The
      subcellular distribution of Dazl was microtubule-dependent and a selected number
      of Dazl-bound mRNAs could accumulate in the perinuclear area. Based on these
      results, we propose that Dazl may play a role in transport of specific mRNAs via
      dynein motor complex. The Dazl-bound mRNAs may be stored at specific sites and
      would be available for future developmental processes. Our study revealed the
      presence of an active mRNA transport system in mouse male germ cells.

PMID- 16946705
TI  - PARP-2 deficiency affects the survival of CD4+CD8+ double-positive thymocytes.
AB  - Poly-(ADP-ribose) polymerase-2 (PARP-2) belongs to a large family of enzymes that
      synthesize and transfer ADP-ribose polymers to acceptor proteins, modifying their
      functional properties. PARP-2-deficient (Parp-2-/-) cells, similar to Parp-1-/-
      cells, are sensitive to both ionizing radiation and alkylating agents. Here we
      show that inactivation of mouse Parp-2, but not Parp-1, produced a two-fold
      reduction in CD4+CD8+ double-positive (DP) thymocytes associated with decreased
      DP cell survival. Microarray analyses revealed increased expression of the
      proapoptotic Bcl-2 family member Noxa in Parp-2-/- DP thymocytes compared to
      littermate controls. In addition, DP thymocytes from Parp-2-/- have a reduced
      expression of T-cell receptor (TCR)alpha and a skewed repertoire of TCRalpha
      toward the 5' Jalpha segments. Our results show that in the absence of PARP-2,
      the survival of DP thymocytes undergoing TCRalpha recombination is compromised
      despite normal amounts of Bcl-xL. These data suggest a novel role for PARP-2 as
      an important mediator of T-cell survival during thymopoiesis by preventing the
      activation of DNA damage-dependent apoptotic response during the multiple rounds
      of TCRalpha rearrangements preceding a positively selected TCR.

PMID- 16946706
TI  - High-resolution cryo-EM maps show the nucleotide binding pocket of KIF1A in open
      and closed conformations.
AB  - Kinesin is an ATP-driven microtubule (MT)-based motor fundamental to organelle
      transport. Although a number of kinesin crystal structures have been solved, the
      structural evidence for coupling between the bound nucleotide and the
      conformation of kinesin is elusive. In addition, the structural basis of the MT
      induced ATPase activity of kinesin is not clear because of the absence of the MT
      in the structure. Here, we report cryo-electron microscopy structures of the
      monomeric kinesin KIF1A-MT complex in two nucleotide states at about 10 A
      resolution, sufficient to reveal the secondary structure. These high-resolution
      maps visualized clear structural changes that suggest a mechanical pathway from
      the nucleotide to the neck linker via the motor core rotation. In addition, new
      nucleotide binding pocket conformations are observed that are different from X
      ray crystallographic structures; it is closed in the 5'-adenylyl-imidodiphosphate
      state, but open in the ADP state. These results suggest a structural model of
      biased diffusion movement of monomeric kinesin motor.

PMID- 16946707
TI  - Physical and functional connection between auxilin and dynamin during
      endocytosis.
AB  - During clathrin-mediated endocytosis, the GTPase dynamin promotes formation of
      clathrin-coated vesicles, but its mode of action is unresolved. We provide
      evidence that a switch in three functional states of dynamin (dimers, tetramers,
      rings/spirals) coordinates its GTPase cycle. Dimers exhibit negative
      cooperativity whereas tetramers exhibit positive cooperativity with respect to
      GTP. Our study identifies tetramers as the kinetically most stable GTP-bound
      conformation of dynamin, which is required to promote further assembly into
      higher order structures such as rings or spirals. In addition, using fluorescence
      lifetime imaging microscopy, we show that interactions between dynamin and
      auxilin in cells are GTP-, endocytosis- and tetramer-dependent. Furthermore, we
      show that the cochaperone activity of auxilin is required for constriction of
      clathrin-coated pits, the same early step in endocytosis known to be regulated by
      the lifetime of dynamin:GTP. Together, our findings support the model that the
      GTP-bound conformation of dynamin tetramers stimulates formation of constricted
      coated pits at the plasma membrane by regulating the chaperone activity of
      hsc70/auxilin.

PMID- 16946708
TI  - Interaction of muscleblind, CUG-BP1 and hnRNP H proteins in DM1-associated
      aberrant IR splicing.
AB  - In myotonic dystrophy (DM1), both inactivation of muscleblind proteins and
      increased levels of CUG-BP1 are reported. These events have been shown to
      contribute independently to aberrant splicing of a subset RNAs. We demonstrate
      that steady-state levels of the splice regulator, hnRNP H, are elevated in DM1
      myoblasts and that increased hnRNP H levels in normal myoblasts results in the
      inhibition of insulin receptor (IR) exon 11 splicing in a manner similar to that
      observed in DM1. In normal myoblasts, overexpression of either hnRNP H or CUG-BP1
      results in the formation of an RNA-dependent suppressor complex consisting of
      both hnRNP H and CUG-BP1, which is required to maximally inhibit IR exon 11
      inclusion. Elevated levels of MBNL1 show RNA-independent interaction with hnRNP H
      and dampen the inhibitory activity of increased hnRNP H levels on IR splicing in
      normal myoblasts. In DM1 myoblasts, overexpression of MBNL1 in conjunction with
      si-RNA mediated depletion of hnRNP H contributes to partial rescue of the IR
      splicing defect. These data demonstrate that coordinated physical and functional
      interactions between hnRNP H, CUG-BP1 and MBNL1 dictate IR splicing in normal and
      DM1 myoblasts.

PMID- 16946710
TI  - Mechanism of RecA-mediated homologous recombination revisited by single molecule
      nanomanipulation.
AB  - The mechanisms of RecA-mediated three-strand homologous recombination are
      investigated at the single-molecule level, using magnetic tweezers. Probing the
      mechanical response of DNA molecules and nucleoprotein filaments in tension and
      in torsion allows a monitoring of the progression of the exchange in real time,
      both from the point of view of the RecA-bound single-stranded DNA and from that
      of the naked double-stranded DNA (dsDNA). We show that strand exchange is able to
      generate torsion even along a molecule with freely rotating ends. RecA readily
      depolymerizes during the reaction, a process presenting numerous advantages for
      the cell's 'protein economy' and for the management of topological constraints.
      Invasion of an untwisted dsDNA by a nucleoprotein filament leads to an exchanged
      duplex that remains topologically linked to the exchanged single strand,
      suggesting multiple initiations of strand exchange on the same molecule. Overall,
      our results seem to support several important assumptions of the monomer
      redistribution model.

PMID- 16946709
TI  - The tumor suppressor protein p53 is required for neurite outgrowth and axon
      regeneration.
AB  - Axon regeneration is substantially regulated by gene expression and cytoskeleton
      remodeling. Here we show that the tumor suppressor protein p53 is required for
      neurite outgrowth in cultured cells including primary neurons as well as for
      axonal regeneration in mice. These effects are mediated by two newly identified
      p53 transcriptional targets, the actin-binding protein Coronin 1b and the GTPase
      Rab13, both of which associate with the cytoskeleton and regulate neurite
      outgrowth. We also demonstrate that acetylation of lysine 320 (K320) of p53 is
      specifically involved in the promotion of neurite outgrowth and in the regulation
      of the expression of Coronin 1b and Rab13. Thus, in addition to its recognized
      role in neuronal apoptosis, surprisingly, p53 is required for neurite outgrowth
      and axonal regeneration, likely through a different post-translational pathway.
      These observations may suggest a novel therapeutic target for promoting
      regenerative responses following peripheral or central nervous system injuries.

PMID- 16946711
TI  - Enhanced survival associated with vitiligo expression during maintenance
      biotherapy for metastatic melanoma.
AB  - Vitiligo, an autoimmune skin disorder, was evaluated in 49 metastatic melanoma
      patients treated with an immunotherapy regimen of maintenance biotherapy (mBT)
      following induction concurrent biochemotherapy (cBCT). Patients receiving mBT
      demonstrated a stable or better response to cBCT. The mBT regimen consisted of
      outpatient subcutaneous injections of low-dose IL-2 (1 MIU/m(2)) 5/7 days weekly,
      GM-CSF (125 mcg/m(2)) 14 days monthly, and high-dose pulses of in-patient
      continuous infusion decrescendo IL-2 (54 MIU/m(2)) over 48 hours monthly for the
      first 6 months and every 2 months thereafter. The majority of patients had poor
      prognostic features. Forty-nine patients were without evidence of vitiligo at the
      start of mBT. Of these, 21 patients (43%) developed vitiligo during mBT and had a
      median overall survival from the start of mBT of 18.2 months (95% CI, 12.3-N/A)
      compared to 8.5 months (95%CI <6.7-12.7) for 28 non-vitiligo patients (P=0.027).
      Six of 21 vitiligo patients (29%) expressed IgG antibody titers to tyrosinase
      related protein-2 compared to four of 28 non-vitiligo patients (14%) (P=NS). The
      development of vitiligo in metastatic melanoma patients on cBCT/mBT immunotherapy
      correlates with a better therapeutic outcome.

PMID- 16946712
TI  - A Web-based data warehouse on gene expression in human malignant melanoma.
AB  - The identification of melanoma-specific dysregulated genes could identify new
      molecular markers. By applying bioinformatic tools for screening of biomedical
      databases, a melanoma-specific gene expression profile "data warehouse" was
      constructed. Utilizable data sets of global gene expression analyses were
      available from nine studies that applied different technology platforms. A single
      study used cell lines, five investigations analyzed cell lines and tissues
      obtained from patients, two studies used exclusively specimens obtained from
      patients, and one study analyzed blood cells prepared from patients. The total
      number of investigated patients was 116. From 815 differential-regulated genes,
      772 (95%) were identified merely in a single study, 37 in at least two studies,
      five (RAB33A, ERBB3, ADRB2, MERTK, SNF1LK, and ITPKB) in at least three studies,
      and a single gene, RAB33A, in four studies. These data show that the accuracy,
      reproducibility, and comparability among different gene expression profile
      studies are low in melanoma. In conclusion, the study demonstrates the high
      diversity of gene expression profiles associated with melanoma, the necessity to
      include a sufficient number of samples regarding clinical standards, for the
      design of standardized sample collecting and preparation, for the development of
      common standards for microarray data processing, and for developing standardized
      bioinformatic tools.

PMID- 16946713
TI  - Quantitative analysis of melanocytic tissue array reveals inverse correlation
      between activator protein-2alpha and protease-activated receptor-1 expression
      during melanoma progression.
AB  - The identification of molecular markers of melanoma progression is needed to more
      accurately stage and identify treatments for patients with malignant melanoma.
      Previously, we demonstrated that loss of the activator protein-2alpha (AP-2alpha)
      expression results in overexpression of the protease-activated receptor-1 (PAR-1)
      in human melanoma cell lines. Here, we used a tissue microarray platform that
      consisted of 64 melanocytic lesions, including dysplastic nevi (N=21), primary
      melanoma (N=20), and metastatic melanoma (N=23). We analyzed the expression of AP
      2 and PAR-1 simultaneously by immunofluorescent microscopy with an automated
      quantification laser scanning cytometer. AP-2 was highly expressed in normal
      cutaneous melanocytes and dysplastic nevi but not in melanoma metastases. We
      observed a significantly higher number of AP-2-positive cells in the dysplastic
      nevi (P=0.0013) and primary melanoma (P=0.0023) compared to the metastatic
      melanoma. In contrast, we observed a significantly higher percentage of PAR-1
      positive cells in the metastatic melanoma compared to dysplastic nevi (P=0.0072)
      and primary melanoma (P=0.0138). Increased expression of PAR-1 in metastatic
      melanomas contributes to tumor progression by modulating expression of genes,
      such as IL-8, matrix metalloproteinase-2, vascular endothelial growth factor,
      platelet-derived growth factor, and integrins. These findings support our
      hypothesis that loss of AP-2 is a crucial event in the progression of human
      melanoma and contributes to the acquisition of the metastatic phenotype via
      upregulation of PAR-1.

PMID- 16946714
TI  - Oxidative stress via hydrogen peroxide affects proopiomelanocortin peptides
      directly in the epidermis of patients with vitiligo.
AB  - The human skin holds the capacity for autocrine processing of the
      proopiomelanocortin (POMC)-derived peptides. Recent data demonstrated the
      presence and functionality of ACTH, alpha- and beta-melanocyte-stimulating
      hormone (MSH), and beta-endorphin in the regulation of skin pigmentation, and a
      role has been put forward for alpha-MSH as an effective antioxidant. In patients
      with vitiligo, decreased epidermal POMC processing and low alpha-MSH levels were
      documented previously. These patients accumulate hydrogen peroxide (H2O2) in the
      10(-3) M range in their epidermis. Therefore, we examined the involvement of H2O2
      on POMC-derived peptides as possible targets for oxidation by this reactive
      oxygen species. To address this, we employed immunofluorescence labelling, dot
      blot analysis, Fourier transform Raman spectroscopy, functionality studies, and
      computer simulation of the peptide structures. We demonstrate H2O2-mediated
      oxidation of epidermal ACTH, alpha-MSH, and beta-endorphin in vitiligo owing to
      oxidation of methionine residues in the sequences of these peptides. Moreover, we
      show that oxidized beta-endorphin loses its function in the promotion of
      pigmentation in melanocytes. These changes are reversible upon the reduction of
      H2O2 levels by a pseudocatalase PC-KUS. Moreover, oxidation of alpha-MSH can be
      prevented by the formation of a 1:1 complex with the abundant cofactor (6R)-L
      erythro-5,6,7,8-tetrahydrobiopterin. Thus, using vitiligo, we demonstrate that
      H2O2 can affect pigmentation via epidermal POMC peptide redox homeostasis.

PMID- 16946715
TI  - Survivin in the human hair follicle.

PMID- 16946716
TI  - Role of cathepsin K in the turnover of the dermal extracellular matrix during
      scar formation.
AB  - Cathepsins are a group of cysteine proteinases that are involved in various
      aspects of extracellular matrix turnover. The collagenolytic activity of
      cathepsin K plays a pivotal role in bone resorption and lung matrix homeostasis,
      but so far has not been described in skin. To study the role of cathepsin K in
      the turnover of the cutaneous extracellular matrix, we studied the expression of
      cathepsin K in human skin and in cultured primary neonatal skin fibroblasts.
      Normal skin exhibited only low levels or no expression of cathepsin K. In
      contrast, dermal fibroblasts in surgical scars showed strong cytoplasmic
      cathepsin K expression. Cathepsin K expression was most prominent in young scars
      and declined with time. Cultured neonatal primary fibroblasts showed strong
      cathepsin K staining in the perinuclear endosomal compartment, consistent with
      intracellular degradation of internalized collagen in lysosomes. Cathepsin K was
      also found to be strongly expressed in keloids and dermatofibromas, but not in
      sclerotic areas of morphea. Our data suggest that cathepsin K may play an
      important role in the homeostasis of the dermal extracellular matrix and the
      dynamic equilibrium between matrix synthesis and proteolytic degradation, by
      counteracting deposition of matrix proteins during scar formation with its matrix
      degrading activity.

PMID- 16946717
TI  - T helper type 2-biased natural killer cell phenotype in patients with pemphigus
      vulgaris.
AB  - Pemphigus vulgaris (PV) is an autoantibody-mediated bullous disease, but the role
      of natural killer (NK) cells in its pathogenic process has never been examined in
      detail. Circulating CD56+ CD3- NK cells as well as CD69+-activated NK cells were
      increased in PV patients compared with healthy controls and patients with other
      autoantibody-mediated autoimmune diseases, including immune thrombocytopenic
      purpura and myasthenia gravis. Gene expression analysis of highly purified NK
      cells demonstrated an increased expression of IL-10 and decreased expression of
      IL-12Rbeta2, perforin, and granzyme B ex vivo in PV patients versus healthy
      controls. The NK cells from PV patients also showed impaired signal transducer
      and activator of transduction4 phosphorylation upon in vitro IL-12 stimulation.
      Moreover, NK cells from PV patients exhibited reduced IL-10 production in
      response to in vitro stimulation with IL-2/IL-12. Finally, IL-5 expression in NK
      cells was exclusively detected ex vivo in PV patients with active disease, and
      was lost in subsequent analyses performed during disease remission. Together
      these findings suggest that NK cells contribute to a T helper type 2-biased
      immune response in PV patients through impaired IL-12 signaling and an
      upregulation of IL-10 and IL-5.

PMID- 16946718
TI  - Extracellular ATP has stimulatory effects on the expression and release of IL-6
      via purinergic receptors in normal human epidermal keratinocytes.
AB  - Extracellular ATP regulates proliferation and differentiation, functioning as an
      important messenger via purinergic (P2) receptors in keratinocytes. In this
      study, we investigated the effects of ATP on cytokine production in cultured
      normal human epidermal keratinocytes (NHEKs). Adenosine 5'-O-(3-thiotriphosphate)
      (ATPgammaS), adenosine 5'-O-2-(thio)diphosphate (ADPbetaS), ADP, ATP, and 2', 3'
      O-(4-benzoyl-benzoyl) ATP (BzATP) significantly increased the release of IL-6.
      The P2 antagonists, suramin-, reactive blue 2-, and periodate-oxidized ATP,
      inhibited ATP-induced IL-6 release, whereas pyridoxal-phosphate-6-azophenyl-2',4'
      disulfonic acid, adenosine 3'-phosphate 5'-phosphate, 1-[N,O-bis(1,5
      isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine, and pertussis toxin
      did not. SQ22563, an adenylate cyclase inhibitor, inhibited ATP-induced IL-6
      release. ATPgammaS, ADPbetaS, ATP, and BzATP significantly increased the
      intracellular cAMP content. Reverse transcription-PCR showed expression of P2Y1,
      P2Y2, P2Y4, P2Y11, P2Y12, P2Y13, P2X1, P2X4, P2X5, P2X6, and P2X7 receptor
      subtypes. Additionally, UVB radiation evoked the release of ATP from NHEKs. The
      release of IL-6 and the expression of IL-6 mRNA were increased after UVB
      radiation, and these increases were also inhibited by P2 receptor antagonists.
      These results suggest that cAMP-generating P2Y receptors are likely functional in
      ATP-induced IL-6 production in NHEKs. Furthermore, in UVB-radiated cells, we note
      the possibility that P2 receptor antagonists may reduce skin inflammation.

PMID- 16946719
TI  - Loss of heterozygosity analysis on chromosome 12q in disseminated superficial
      actinic porokeratosis.

PMID- 16946720
TI  - Where have all the chemists gone?

PMID- 16946721
TI  - Self-organized growth controlled by charge states of magnetic impurities.

PMID- 16946723
TI  - Solar cells: Pictures from the blended zone.

PMID- 16946724
TI  - Spintronics: Magnetism's ticklish giant.

PMID- 16946725
TI  - Materials for energy: From fission towards fusion.

PMID- 16946726
TI  - Zeolites: Large molecules welcome.

PMID- 16946728
TI  - Excitons in nanoscale systems.
AB  - Nanoscale systems are forecast to be a means of integrating desirable attributes
      of molecular and bulk regimes into easily processed materials. Notable examples
      include plastic light-emitting devices and organic solar cells, the operation of
      which hinge on the formation of electronic excited states, excitons, in complex
      nanostructured materials. The spectroscopy of nanoscale materials reveals details
      of their collective excited states, characterized by atoms or molecules working
      together to capture and redistribute excitation. What is special about excitons
      in nanometre-sized materials? Here we present a cross-disciplinary review of the
      essential characteristics of excitons in nanoscience. Topics covered include
      confinement effects, localization versus delocalization, exciton binding energy,
      exchange interactions and exciton fine structure, exciton-vibration coupling and
      dynamics of excitons. Important examples are presented in a commentary that
      overviews the present understanding of excitons in quantum dots, conjugated
      polymers, carbon nanotubes and photosynthetic light-harvesting antenna complexes.

PMID- 16946729
TI  - Caspase inhibitors: viral, cellular and chemical.
AB  - Caspases, key mediators of apoptosis, are a structurally related family of
      cysteine proteases that cleave their substrates at aspartic acid residues either
      to cause cell death or to activate cytokines as part of an immune response. They
      can be controlled upstream by the regulation of signals that lead to zymogen
      activation, or downstream by inhibitors that prevent them from reaching their
      substrates. This review specifically looks at caspase inhibitors as distinct from
      caspase regulators: those produced by the cell itself; those whose genes are
      carried by viruses; and artificial caspase inhibitors used for research and
      potentially as therapeutics.

PMID- 16946731
TI  - DNA damaging agent-induced autophagy produces a cytoprotective adenosine
      triphosphate surge in malignant glioma cells.
AB  - Although autophagy enhances cell survival in nutrient-deprived cells by
      increasing adenosine triphosphate (ATP) production, it remains unclear if
      autophagy functions similarly in cells treated with cytotoxic chemotherapy
      agents. To address this issue, we measured both the ability of DNA damaging
      agents (Temozolomide, and Etoposide) to induce an autophagy-dependent production
      of ATP, and the effects of modulation of autophagy on drug-induced cell death.
      Both drugs induced an autophagy-associated increase in ATP production in multiple
      glioma cell lines. The drug-induced ATP surge could not be blocked by glucose
      starvation, but could be blocked by preincubation with the autophagy inhibitor 3
      methyladenine (3-MA), an siRNA targeting beclin 1, or the mitochondrial inhibitor
      oligomycin. Inhibition of autophagy-induced ATP production increased non
      apoptotic cell death associated with micronucleation, while restoration of the 3
      MA-inhibited ATP surge by addition of pyruvate suppressed cell death. These
      results show that DNA damaging agents induce an autophagy-associated ATP surge
      that protects cells and may contribute to drug resistance.

PMID- 16946732
TI  - Elucidation of some Bax conformational changes through crystallization of an
      antibody-peptide complex.
AB  - The Bcl-2 family member Bax plays a critical role in apoptosis. In healthy
      resting cells, Bax resides in the cytoplasm and loosely attached to the
      mitochondrial membrane. Apoptotic stimuli induce Bax activation, which is
      characterized by translocation and multimerization on the mitochondrial membrane
      surface resulting in exposure of an amino terminal epitope recognized by the
      monoclonal antibody 6A7. To understand the structural changes that occur during
      Bax activation, we determined the crystal structure of a Bax peptide bound to the
      6A7 Fab fragment to a resolution of 2.3 A. The structure reveals the conformation
      of the 6A7 peptide epitope on Bax in the activated form and elucidates the
      extensive structural changes that Bax must undergo during the conversion from its
      native to its activated conformation.

PMID- 16946733
TI  - Innate ability is academic.

PMID- 16946735
TI  - Only one spindle, if you please....

PMID- 16946736
TI  - Kinesin-8s: motoring and depolymerizing.

PMID- 16946737
TI  - Src transforms in a Cool way.

PMID- 16946738
TI  - CFTR: helping to acidify macrophage lysosomes.

PMID- 16946739
TI  - Meiosis: separase strikes twice.

PMID- 16946742
TI  - Uveal malignant melanoma with extrascleral extension, treated with plaque
      radiotherapy.

PMID- 16946743
TI  - Precautions in ophthalmic practice in a hospital with a major acute SARS
      outbreak: an experience from Hong Kong.

PMID- 16946744
TI  - Precautions in ophthalmic practice in a hospital with a major acute SARS
      outbreak: an experience from Hong Kong.

PMID- 16946745
TI  - Scleral penetration force requirements for commonly used intravitreal needles.
AB  - INTRODUCTION: Repeated intraocular injections have become routine practice. It is
      important to determine how to make them as painless as possible. We wished to
      examine the force required to penetrate the sclera with different gauge needles.
      METHODS: Recently enucleated eyes had 4 mm scleral punch biopsies performed. The
      scleral disks were mounted on a fixed load cell and either a new needle or a
      needle that had previously penetrated a rubber vial was attached to a linear
      stage and the maximum penetration force measured. RESULTS: The 27-gauge needles
      required almost twice as much force to penetrate the sclera than either the 30-
      or the 31-gauge. In addition, the 30- and 31-gauge appeared to require similar
      force. In all cases, following vial perforation, there was an increase in the
      amount of force required to penetrate the sclera. The amount of force was
      variable. DISCUSSION: Smaller gauge needles require less force to penetrate the
      sclera and needles that have been used to penetrate rubber vials require more
      force.

PMID- 16946746
TI  - Intraocular pressure measurement in mice: a comparison between Goldmann and
      rebound tonometry.
AB  - PURPOSE: The development of mouse models of glaucoma requires methods to
      accurately measure the intraocular pressure (IOP) in this species. The aim of
      this study was to compare the accuracy of IOP measurements in mice between
      modified Goldmann and rebound tonometers. METHODS: IOP was measured either with a
      modified Goldmann or a rebound tonometer while simultaneously measuring the IOP
      using invasive manometry in enucleated eyes and in vivo. The level of IOP was
      controlled hydrostatically. The agreement and correlation between the IOP
      determined by invasive manometry and by either noninvasive method was evaluated.
      In addition, the IOP was determined by both noninvasive methods in a cohort of
      mice with laser-induced ocular hypertension (OHT), and the agreement and
      correlation between the two tonometry methods were evaluated. RESULTS: Measured
      IOP by either noninvasive tonometer correlated well with those recorded
      simultaneously by invasive manometry (r=0.98 for rebound and r=0.94 for
      Goldmann). In mice with OHT, the IOP correlation between rebound and modified
      Goldmann was moderate (r=0.71); the IOP measured by modified Goldmann tonometry
      was consistently higher than that by rebound by approximately 5 mmHg. However,
      the relative per cent increases in IOP were similar between the two methods.
      CONCLUSION: Both noninvasive methods of IOP measurements in mice are suitable to
      detect changes in IOP although rebound tonometry correlated better with the
      invasive manometry readings. The results suggest that the relative, rather than
      absolute, IOP offers a more reliable means of correlating findings from studies
      using different tonometers.

PMID- 16946747
TI  - Inadvertent injection of triamcinolone into the crystalline lens.

PMID- 16946748
TI  - Long-term results of Nd:YAG laser treatment for premacular subhyaloid haemorrhage
      owing to Valsalva retinopathy.
AB  - AIMS: Valsalva retinopathy produces sudden visual loss, which may be prolonged if
      untreated. Nd:YAG laser enables rapid diffusion of premacular subhyaloid
      haemorrhage. This study was performed to assess the long-term results and safety
      of Nd:YAG laser treatment in cases with Valsalva retinopathy. METHODS: Sixteen
      patients had Nd:YAG laser treatment to drain premacular haemorrhage. The follow
      up period was 24 months. RESULTS: All eyes had marked clearing of haemorrhage and
      immediate improvement of vision following laser treatment. In 14 eyes visual
      acuity improved to 20/20 level at the end of the first week and the remaining two
      patients achieved 20/20 level within 1 month. No patient had evidence of retinal
      or choroidal damage. CONCLUSION: Nd:YAG laser treatment for Valsalva retinopathy
      is an effective, non-invasive, and safe procedure for patients with a premacular
      subhyaloid haemorrhage larger than 3 disc diameter and no longer than 3 weeks of
      duration.

PMID- 16946749
TI  - Peripheral and posterior pole retinal lesions in association with high myopia: a
      cross-sectional community-based study in Hong Kong.
AB  - PURPOSE: To evaluate the prevalence and factors associated with posterior pole
      and peripheral retinal lesions in Chinese subjects with high myopia. METHODS:
      Three hundred and thirty-seven asymptomatic adults with high myopia of refractive
      error <or=-6 D were examined in a cross-sectional community-based study. All
      subjects underwent cycloplegic refraction, ultrasound biometry and dilated fundal
      examination. Statistical analysis was performed to assess factors associated with
      the presence of posterior pole and peripheral retinal lesions. RESULTS: The mean
      age of the 337 subjects was 36.0 years and the mean spherical equivalent
      refractive error was -10.2 D. Thirty-eight eyes (11.3%, 95% CI=8.1-15.2%) were
      found to have one or more posterior pole lesions and subjects with posterior pole
      lesion had significantly older age, longer axial length and higher degree of
      myopia (all P<0.001) compared with subjects without posterior pole lesion. After
      controlling for axial length, both the severity of refractive error and older age
      were significantly associated with the presence of posterior pole lesion (both
      P<0.001). For peripheral retinal lesions, 189 eyes (56.1%, 95% CI=50.6-61.5%)
      were found to have one or more peripheral retinal lesions. The presence of
      peripheral retinal lesion was associated with younger age and higher degree of
      refractive error (P=0.046 and 0.002, respectively). CONCLUSION: Posterior pole
      and peripheral retinal degenerative lesions were found in a considerable
      proportion of subjects with high myopia. As some of these retinal lesions might
      predispose to visual impairment, highly myopic individuals should be educated on
      the symptoms of various eye conditions and seek care immediately if symptoms
      arise.

PMID- 16946752
TI  - Screening amblyopia of preschool children with uncorrected vision and stereopsis
      tests in Eastern Taiwan.
AB  - AIMS OR PURPOSE: Screening for amblyopia at earliest age is important for early
      treatment and better prognosis. This study aimed at evaluating the validity of
      uncorrected distant and near visual acuity and random dot stereopsis for
      screening amblyopia. METHODS; In Eastern Taiwan, population-based screen tests
      were performed for children at age from 3 to 6 years. The tests included
      uncorrected distant and near visions and random dot stereopsis (300 s) test. The
      screen performers were registered nurses of local public health service posts.
      The golden standards of the tests were the results of examination by the
      ophthalmologists. RESULTS: Including Hans and aboriginal Taiwanese, 5232 children
      were included. Screened by distance visual acuity with different cutoffs and near
      visual acuity, 10.3, 30.3 and 8.2% children were abnormal. Screened by random
      dot, only 2% children were abnormal. By a senior ophthalmologist, 115 amblyopic
      children were diagnosed amblyopic. The sensitivities of distance visual acuity
      with low/high cutoff and near visual acuity were 74.7/84.8 and 49.4%, whereas
      that of the NTU random dot stereogram was 20.5%. Simultaneous testing of either
      two of the three tests improved the sensitivity. CONCLUSION: Screening for
      amblyopia by the local nurses using the visual acuity tests or random dot
      stereopsis test alone does not display a high sensitivity. Simultaneous testing
      of distant visual acuity and stereopsis test elevate the sensitivity and preserve
      the specificity.

PMID- 16946754
TI  - Dye-assisted small incision cataract surgery in an eye with cataract and
      coexisting corneal scarring and epithelial disease.

PMID- 16946755
TI  - Scleral buckling combined with vitrectomy for the management of rhegmatogenous
      retinal detachment associated with inferior retinal breaks.
AB  - AIM: The use of adjunctive scleral buckling during vitrectomy for retinal
      detachment associated with inferior breaks has been the recent focus of some
      debate. It has been suggested that any benefit might be outweighed by potential
      complications associated with buckling surgery. The purpose of this study was to
      compare the success rate of vitrectomy, gas, and supplementary scleral buckling
      with the results of two recently published case series suggesting that acceptable
      results in inferior break detachments can be achieved with vitrectomy and gas
      alone. METHODS: A retrospective analysis of 60 consecutive patients with inferior
      break retinal detachments was conducted. All patients underwent vitrectomy, gas,
      and scleral buckling. In all cases, fellow eyes were examined under anaesthesia
      for retinal breaks if posterior vitreous detachment (PVD) had occurred at the
      time of presentation. Demographics, preoperative, and postoperative complications
      and outcome were recorded. RESULTS: Primary retinal attachment at 3 months was
      achieved in 95% of patients. This exceeds success rates of published data of
      patients who underwent vitrectomy and gas without buckling (81-89%). In patients
      with PVD in the fellow eye, 53% had horseshoe tears and all were treated with
      cryopexy. No sight-threatening complications occurred, but five patients
      developed minor buckle-related complications postoperatively. CONCLUSION:
      Supplementary scleral buckling is a safe procedure that improves and enhances
      primary success rates in inferior break detachments over vitrectomy and gas
      without buckling. There is a high rate of PVD-related breaks requiring treatment
      in the fellow eyes.

PMID- 16946756
TI  - Unilateral amiodarone keratopathy: occlusive contact lens spares development in
      the contralateral eye.

PMID- 16946757
TI  - Cessation of migraines in a woman with low-tension glaucoma following the use of
      latanoprost: a favourable side effect?

PMID- 16946758
TI  - Comparison of visual acuity outcomes in predominantly classic vs occult lesions
      in age-related macular degeneration treated with photodynamic therapy.
AB  - PURPOSE: To determine if patients with occult with no classic and predominantly
      classic (PC) choroidal neovascular membranes have clinically equivalent visual
      outcomes after treatment with photodynamic therapy (PDT) with verteporfin.
      METHODS: This is a retrospective, observational cohort study. Two hundred and
      seventy-seven consecutive patients with occult or PC choroidal neovascularization
      secondary to age-related macular degeneration treated with PDT were included. The
      main outcome was the difference in mean change in Early Treatment of Diabetic
      Retinopathy Study (ETDRS) acuity lost from baseline in occult vs PC lesions, with
      the minimal clinically important difference (MCID) set at 7.5 letters. RESULTS:
      At baseline, 131 patients had occult and 146 had PC choroidal neovascularization.
      Twelve-month follow-up data were available for 94 occult and 110 PC participants.
      Occult patients lost an average of 8.7 letters (1.9 lines), and patients in the
      PC group an average of 10.0 ETDRS letters (two lines) over 12 months. The mean
      letters lost at 12 months was not significantly different between the groups, and
      the MCID was not detected (difference=1.3 letters; P=0.411; 95% confidence
      interval (-2.3, 5.6)). Patients with occult lesions required a mean of 2.99
      treatments vs a mean of 2.96 treatments in the PC group (out of a possible 4;
      P=0.172). CONCLUSION: We were not able to detect a clinically important
      difference in mean change in visual acuity with PDT treatment between patients
      with occult and PC lesions.

PMID- 16946759
TI  - Palpebral pleomorphic rhabdomyosarcoma in a teenager.

PMID- 16946760
TI  - Keratoconus in tuberous sclerosis.

PMID- 16946761
TI  - Lacrimal drainage surgery in patients with rare nasal diseases.
AB  - AIM: To examine the results of open lacrimal drainage surgery in patients with
      rare nasal diseases. METHOD: A retrospective review of a group of patients with
      rare nasal disease who underwent open lacrimal surgery over a 15-year period at
      Moorfields Eye Hospital. Three main groups of disease were identified: (I)
      patients with treated mid-face tumours; (II) patients with prior major midfacial
      injury or surgery; and (III) patients with congenital nasal anomalies, including
      nasal aplasia. The more common systemic conditions of Wegener's granulomatosis
      and sarcoidosis were specifically excluded. RESULTS: Eighty-six patients (43 men;
      50%) were identified with an age range between 1 and 82 years at the time of
      surgery. A total of 100 primary procedures were performed in 85 patients and
      symptomatic relief was achieved in 83/100 (83%) eyes, with 18/100 eyes (18%)
      requiring two or more lacrimal procedures. Lacrimal reconstructive surgery was
      considered impractical in two further patients. There were no intraoperative and
      few postoperative complications. CONCLUSION: With adequate experience, open
      lacrimal surgery appears to be a safe and effective procedure in the majority of
      patients with rare nasal diseases or major nasofacial anomalies.

PMID- 16946762
TI  - Diffractive element design for resonant scanner angular correction.
AB  - We propose an optical corrective element with zooming capability to convert
      nonlinear sinusoidal scanning into linear scanning. Such a device will be useful
      for linearizing the angular scan of a resonant mirror scanner. The design
      methodology is to create a graded index of refraction device as the reference
      design, with its index of refraction parameters based on the propagation of an
      electromagnetic field in inhomogeneous media. The algorithm for converting this
      refractive element to the corresponding binary diffractive version is also
      presented. Design and simulation data are shown.

PMID- 16946763
TI  - Fabrication and characterization of a diffraction-grating transducer in thin
      polybutadiene rubber film for sensing dynamical strain.
AB  - Surface relief gratings are holographically fabricated in thin polybutadiene
      rubber films produced by both spin coating and dip coating on glass and metal
      substrates. These thin-film gratings are characterized for their application as
      efficient transducers for detecting dynamic strain in solids. The performance of
      these rubber-grating transducers is compared to surface-mounted fiber Bragg
      gratings for a range of frequencies between 50 Hz and 30 kHz. Dynamic-strain
      sensitivity around 1 nepsilon/radicalHz is recorded for thin rubber-film grating
      transducers.

PMID- 16946764
TI  - Diffracted wavefront measurement of a volume phase holographic grating at
      cryogenic temperature.
AB  - Flatness of the wavefront diffracted by grating can be mandatory for some
      applications. At ambient temperature, the wavefront diffracted by a volume phase
      holographic grating (VPHG) is well mastered by the manufacturing process and can
      be corrected or shaped by postpolishing. However, to be used in cooled infrared
      spectrometers, VPHGs have to stand and work properly at low temperatures. We
      present the measurement of the wavefront diffracted by a typical VPHG at various
      temperatures down to 150 K and at several thermal inhomogeneity amplitudes. The
      particular grating observed was produced using a dichromated gelatine technique
      and encapsulated between two glass blanks. Diffracted wavefront measurements show
      that the wavefront is extremely stable according to the temperature as long as
      the latter is homogeneous over the grating stack volume. Increasing the thermal
      inhomogeneity increases the wavefront error that pinpoints the importance of the
      final instrument thermal design. This concludes the dichromated gelatine VPHG
      technology, used more and more in visible spectrometers, can be applied as it is
      to cooled IR spectrometers.

PMID- 16946765
TI  - Study of a dynamic-shape-curve function for a fused tapering optical fiber.
AB  - For the fused tapering optical fibers, a physics-mathematics equation of dynamic
      shape curves is deduced. The closed-form solution of the equation can be acquired
      by use of its initial, boundary, and volume-conserved conditions. The shape
      curves in different tapering processes can be described by the solution
      conveniently, accurately, and integratively. A large quantity of experimental
      data has been provided and shown to have a coincidence with the theoretical
      results properly. Especially, the initial length of the fused zone is known, and
      the solution can predict the whole tapering shape curve with an arbitrary
      elongating length.

PMID- 16946766
TI  - Theoretical development of in situ optical particle separator: cross-type optical
      chromatography.
AB  - An in situ separation system, cross-type optical chromatography, is developed
      theoretically, and an analytic solution of the retention distance is derived.
      Particle trajectories in the cross-type optical chromatography are calculated for
      various sizes and materials of the particles and for flow velocities. Further,
      cross-type optical chromatography assisted by a particle beam generation system
      is designed.

PMID- 16946767
TI  - Low-order aberration corrections of multilayer flat lenses using negative-index
      materials.
AB  - A study of the corrections for some low-order aberrations of multilayer flat
      lenses based on the introduction of negative-index materials is presented. With
      the aberration coefficients of a multilayer flat lens that we provided, numerical
      solutions for the parameters of the double-layer three-layer, and four-layer flat
      lenses are investigated, respectively, to correct the aberrations, under some
      conditions, up to orders as high as possible. We find that with the increment of
      the layer number, the spherical and oblique aberrations can be corrected up to
      higher orders though the corresponding ranges of the refractive indices and
      working distances become narrower.

PMID- 16946768
TI  - Speckle correlation method used to detect an object's surface slope.
AB  - We present a technique employing a speckle pattern correlation method for
      detection of the slope of an object's surface. Controlled translation of an
      object under investigation and numerical correlation of speckle patterns recorded
      during its motion give information used to evaluate the tilt of the object. The
      proposed optical setup uses a symmetrical arrangement of detection planes in the
      image field and enables one to detect the tilt of an object's surface within the
      interval (10 degrees-30 degrees). Simulation analysis shows how to control the
      measuring range. The presented theory, simulation analysis, and setup are
      verified through an experiment by measurement of the slope of a surface of a cube
      made out of steel.

PMID- 16946769
TI  - Accurate pixel-to-pixel correspondence adjustment in a digital micromirror device
      camera by using the phase-shifting moire method.
AB  - A camera based on the digital micromirror device (DMD) technology has been
      previously developed. In this optical system, the correspondence of each mirror
      of the DMD to each pixel of the CCD cannot readily be done since the pixel sizes
      of the DMD and the CCD are very small. An accurate pixel-to-pixel correspondence
      adjustment in the DMD camera by means of the phase-shifting moire method is
      proposed. To perform high accurate adjustment of the optical system, the phase
      distribution of a moire fringe pattern is analyzed when the CCD pixels and the
      DMD mirrors have a mismatch and/or misalignment with each other. This technique
      does not need a complicated setting or complex image processing to generate the
      moire fringe pattern, and it needs only one captured image. In the adjustment
      experiment, the proposed method provided very accurate adjustment whose error was
      less than 1/25 pixel. An experiment of phase analysis to demonstrate the
      usefulness was performed.

PMID- 16946770
TI  - High-resolution mapping of quantum efficiency of silicon photodiode via optical
      feedback laser microthermography.
AB  - We map the external quantum efficiency (QE) distribution of a silicon photodiode
      (PD) sample via a thermographic imaging technique based on optical-feedback laser
      confocal microscopy. An image pair consisting of the confocal reflectance image
      and the 2D photocurrent map is simultaneously acquired to delineate the following
      regions of interest on the sample: the substrate, the n-type region, the pn
      overlay, and the bonding pad. The 2D QE distribution is derived from the
      photocurrent map to quantify the optical performance of these sites. The thermal
      integrity of the sample is then evaluated by deriving the rate of change of QE
      with temperature T at each point on the silicon PD. These gradient maps function
      not only as stringent measures of local thermal QE activity but they also expose
      probable defect locations on the sample at high spatial resolution--a capability
      that is not feasible with existing bulk measurement techniques.

PMID- 16946771
TI  - Comparison of cubic B-spline and Zernike-fitting techniques in complex wavefront
      reconstruction.
AB  - We analyze an alternative to classical Zernike fitting based on the cubic B
      spline model, and compare the strengths and weaknesses of each representation
      over a set of different wavefronts that cover a wide range of shape complexity.
      The results obtained show that a Zernike low-degree polynomial expansion or a
      cubic B-spline with a low number of breakpoints are the best choices for fitting
      simple wavefronts, whereas the cubic B-spline approach performs much better when
      more complex wavefronts are involved. The effect of noise level in the fit
      quality for the different wavefronts is also studied.

PMID- 16946772
TI  - Improved optical profiling using the spectral phase in spectrally resolved white
      light interferometry.
AB  - In spectrally resolved white-light interferometry (SRWLI), the white-light
      interferogram is decomposed into its monochromatic constituent. The phase of the
      monochromatic constituents can be determined using a phase-shifting technique
      over a range of wavelengths. These phase values have fringe order ambiguity.
      However, the variation of the phase with respect to the wavenumber is linear and
      its slope gives the absolute value of the optical-path difference. Since the path
      difference is related to the height of the test object at a point, a line profile
      can be determined without ambiguity. The slope value, though less precise helps
      us determine the fringe order. The fringe order combined with the monochromatic
      phase value gives the absolute profile, which has the precision of phase-shifting
      interferometry. The presence of noise in the phase may lead to the
      misidentification of fringe order, which in turn gives unnecessary jumps in the
      precise profile. The experimental details of measurement on standard samples with
      SRWLI are discussed in this paper.

PMID- 16946773
TI  - Trithiocarbonate-mediated free-radical photopolymerization: improved uniformity
      in hologram recording.
AB  - A holographic material based on a photopolymerizable nematic acrylate was
      improved by the addition of the trithiocarbonate, EtO2CCH2SC(S)SCH2CO2Et,
      increasing uniformity and reproducibility in the formation of electrically
      switchable holographic gratings. Diffraction efficiencies as high as 34%, the
      thin-grating theoretical maximum, were achieved at large (10-14 microm) grating
      spacings. Improved diffraction efficiency was seen over a range of grating
      spacings (0.35-10 microm). The exposure window for grating formation was
      increased by an order of magnitude, resulting in much improved reproducibility.

PMID- 16946774
TI  - Laser micromachining of goldblack coatings.
AB  - Goldblack deposits have been used as high-absorption coatings for thermal
      infrared detectors for a number of years, principally on large single, or few
      pixel detectors. We present a new technique that allows the benefits of goldblack
      to be applied to the current generation of small pixel silicon micromachined
      thermal infrared detectors.

PMID- 16946775
TI  - Achromatic half-wave plate for submillimeter instruments in cosmic microwave
      background astronomy: experimental characterization.
AB  - An achromatic half-wave plate (HWP) to be used in millimeter cosmic microwave
      background (CMB) polarization experiments has been designed, manufactured, and
      tested. The design is based on the 5-plates Pancharatnam recipe and it works in
      the frequency range 85-185 GHz. A model has been used to predict the
      transmission, reflection, absorption, and phase shift as a function of frequency.
      The HWP has been tested by using coherent radiation from a back-wave oscillator
      to investigate its modulation efficiency and with incoherent radiation from a
      polarizing Fourier transform spectrometer (FTS) to explore its frequency
      behavior. The FTS measurements have been fitted with an optical performance model
      which is in excellent agreement with the data. A detailed analysis of the data
      also allows a precise determination of the HWP fast and slow axes in the
      frequency band of operation. A list of the HWP performance characteristics is
      reported including estimates of its cross polarization.

PMID- 16946776
TI  - Experimental results on piston detection by using the classical Ronchi test.
AB  - We present some experimental results of piston detection by using a classical
      Ronchi test in a segmented spherical surface. We compare the Ronchi fringes
      frequency of both segments (reference and under test). When the piston term is
      present at the segment under test, it is moved iteratively until we obtain a
      minimum piston error. When the surface is almost cophased, both segments have the
      same fringe frequency. The fringes of each segment are compared by correlating
      the intensity versus position in each segment. The Ronchi test is used at the
      same time as Shack interferometry; this second method is used as a reference to
      avoid segments tilts. With the Ronchi test we have detected experimentally a
      piston of the order of 45 nm (lambda/14 with lambda=632.8 nm). This result was
      compared with images of simulated Ronchigrams.

PMID- 16946777
TI  - Hybrid imaging using linear retroreflectors.
AB  - It has been observed that retroreflective materials can be used in combination
      with beam splitters to produce real images. This is practical on a large size
      scale but has a maximum optical efficiency of 25%. Conversely, curved reflectors
      efficiently produce real images, but their cost increases very rapidly with size.
      We introduce a new imaging method, which combines the advantages of both systems,
      through the use of a linear retroreflective film. This material is
      retroreflective in one plane and conventionally reflective in the perpendicular
      plane. The net result is an efficient real image system that can have unlimited
      extent in one transverse direction, and which can be inexpensively manufactured
      on a large scale.

PMID- 16946778
TI  - Refractive effects in coherent anti-Stokes Raman scattering microscopy.
AB  - Coherent anti-Stokes Raman scattering (CARS) microscopy with high sensitivity and
      high three- dimensional resolution has been developed for the vibrational imaging
      of chemical species. Due to the coherent nature of the CARS emission, it has been
      reported that the detection of epi-CARS and forward-CARS (F-CARS) signals depends
      on the size and shape of the sample. We investigate theoretically and
      experimentally the effects on the CARS signal of refractive index mismatches
      between the sample and its surroundings. Backward-CARS and F-CARS signals are
      measured for different polystyrene bead diameters embedded in different
      refractive index solvents. We show that index mismatches result in a backward
      reflected F-CARS signal that generally dominates the experimentally backward
      detected signal. Simulations based on geometrical and wave optics comparing
      forward- and backward-detected signals for polystyrene beads embedded in
      different index solvents confirm our findings. Furthermore, we demonstrate that
      the maxima of forward- and backward-detected signals are generated at different
      positions along the optical axis in the sample if refractive index mismatches are
      present between the sample and its surroundings.

PMID- 16946779
TI  - Influence of multiple reflections on transmission through a stack of plates.
AB  - We examine the problem of light transmission along the normal through a stack of
      flat plates whose thicknesses and separations vary. For a modest number of
      plates, an exact calculation is straightforward, but then one must address how to
      average over both the disorder in the stack and the distribution of incident
      wavelengths. Model calculations are used to show that an average over the light's
      distribution can suppress most of the fluctuations due to disorder. Our results
      are in qualitative agreement with experimental data and imply that multiple
      reflections do contribute significantly to the measurements. Finally we explore
      the effect of multiple reflections on photometry.

PMID- 16946780
TI  - Diffuse light propagation in a turbid medium with varying refractive index: Monte
      Carlo modeling in a spherically symmetrical geometry.
AB  - We report on the development of Monte Carlo software that can model media with
      spatially varying scattering coefficient, absorption, and refractive index. The
      varying refractive index is implemented by calculating curved photon paths in the
      medium. The results of the numerical simulations are compared with analytical
      solutions obtained using the diffusion approximation. The model under
      investigation is a scattering medium that contains a spherically symmetrical
      inclusion (inhomogeneity) created by variation in optical properties and having
      no sharp boundaries. The following steady-state cases are considered: (a) a
      nonabsorbing medium with a spherically symmetrical varying refractive index, (b)
      an inclusion with varying absorption and scattering coefficients and constant
      refractive index, and (c) an inclusion with varying absorption, scattering, and
      refractive index. In the latter case it is shown that the interplay between the
      absorption coefficient and the refractive index may create the effect of a hidden
      inclusion.

PMID- 16946781
TI  - Investigation of the effect of accumulation of thickness errors in optical
      coating production by broadband optical monitoring.
AB  - We present a theoretical approach enabling one to perform a preproduction
      investigation of the effect of accumulation of thickness errors in the course of
      optical coating production using broadband optical monitoring. On the basis of
      this approach we investigate and compare thickness errors that may be associated
      with such factors as random and systematic errors in measurement data,
      instabilities of deposition rates, and inaccuracies of on-line algorithms
      predicting termination instants for layer depositions.

PMID- 16946782
TI  - Selective erasure of speckle-multiplexed holograms by use of a double Mach
      Zehnder interferometric arrangement.
AB  - A novel method to selectively erase and update speckle-multiplexed holograms in
      photorefractive crystals by use of a double Mach-Zehnder (DMZ) interferometric
      arrangement is presented. The DMZ arrangement automatically produces a pair of pi
      phase-shifted interference patterns used for holographic recording, erasure, and
      update operations with a fairly simple optical configuration that consists of a
      commonly used dielectric multilayer beam splitter and two mirrors. The recording
      and the erasure conditions required for erasing a photorefractive hologram
      quickly and completely are discussed by calculating the temporal property of the
      hologram buildup and decay using the time-dependent coupled-wave equations. An
      experiment is also performed, in which arbitrary holograms in speckle-multiplexed
      holograms are selectively erased and updated with the simple DMZ optical
      configuration.

PMID- 16946783
TI  - State estimation approach for determining composition and growth rate of Si1-xGex
      chemical vapor deposition utilizing real-time ellipsometric measurements.
AB  - We present an algorithm that simultaneously deduces from real-time ellipsometric
      measurements both the growth rate and the composition of Si1-xGex films deposited
      via chemical vapor deposition. The heart of the algorithm is a dynamic, first
      principles model of the deposition system and the ellipsometric sensor. The model
      predicts the ellipsometric parameters psi and Delta during film growth. An
      extended Kalman filter is developed that utilizes the sensor model and infers
      both the growth rate and the Ge composition of the deposited film in real time.
      Two simulations demonstrating the effectiveness of the algorithm are evaluated.

PMID- 16946784
TI  - 4Pi microscopy deconvolution with a variable point-spread function.
AB  - To remove the axial sidelobes from 4Pi images, deconvolution forms an integral
      part of 4Pi microscopy. As a result of its high axial resolution, the 4Pi point
      spread function (PSF) is particularly susceptible to imperfect optical conditions
      within the sample. This is typically observed as a shift in the position of the
      maxima under the PSF envelope. A significantly varying phase shift renders
      deconvolution procedures based on a spatially invariant PSF essentially useless.
      We present a technique for computing the forward transformation in the case of a
      varying phase at a computational expense of the same order of magnitude as that
      of the shift invariant case, a method for the estimation of PSF phase from an
      acquired image, and a deconvolution procedure built on these techniques.

PMID- 16946785
TI  - Acousto-optic parallel read/write head for optical disk data storage.
AB  - Parallel read and write of optical disks has traditionally used a static grating
      for read or a linear array of independent lasers for read and write. Depending on
      the implementation, these systems suffer from coherent cross talk, excessive
      space between spots, and an inability to independently track. We show that a
      dynamic acousto-optic grating can generate multiple parallel read/write spots on
      the disk, each of which can be independently modulated and tracked and all of
      which are incoherent in less that a bit period. The resulting disk pickup can
      potentially reach gigabit per second transfer rates with only a modest increase
      in the drive complexity.

PMID- 16946786
TI  - Validation of the Raman lidar algorithm for quantifying aerosol extinction.
AB  - To calculate aerosol extinction from Raman lidar data, it is necessary to
      evaluate the derivative of a molecular Raman signal with respect to range. The
      typical approach taken in the lidar community is to make an a priori assumption
      about the functional behavior of the data to calculate the derivative. It has
      previously been shown that the use of the chi-squared technique to determine the
      most likely functional behavior of the data prior to actually calculating the
      derivative eliminates the need for making a priori assumptions. Here that
      technique is validated through numerical simulation and by application to a
      significant body of Raman lidar measurements. In general, we show that the chi
      squared approach for evaluating extinction yields lower extinction uncertainty
      than traditional techniques. We also use the technique to study the feasibility
      of developing a general characterization of the extinction uncertainty that could
      permit the uncertainty in Raman lidar aerosol extinction measurements to be
      estimated accurately without the need of the chi-squared technique.

PMID- 16946787
TI  - Rough ocean surface and sunglint region characteristics.
AB  - The sunglint geometrical optics equations of a statistically faceted sea,
      supported by the so-called interaction probability density and employing an
      averaging hybrid of the Cox-Munk and Mermelstein slope statistics, was successful
      in simulating 0.5 microm sunglint region characteristics. The results match
      independent experimental data, and good agreement is reported for various sea
      conditions and Sun locations, on sunglint amplitude, sunglint location, and
      azimuth range. In particular, the peak reflectance shift from the specular
      direction toward the horizon is correctly predicted, and it is found that the
      physical mechanism responsible for the shift is the accumulation of contributing
      facets near the horizon.

PMID- 16946788
TI  - Turbulence-induced measurement errors in coherent differential absorption lidar
      ground systems.
AB  - The presence of atmospheric refractive turbulence makes it necessary to use
      simulations of beam propagation to examine the uncertainty added to the
      differential absorption lidar (DIAL) measurement process of a practical
      heterodyne lidar. The inherent statistic uncertainty of coherent return
      fluctuations in ground lidar systems profiling the atmosphere along slant paths
      with large elevation angles translates into a lessening of accuracy and
      sensitivity of any practical DIAL measurement. This technique opens the door to
      consider realistic, nonuniform atmospheric conditions for any DIAL instrument
      configuration.

PMID- 16946789
TI  - Emissitivity spectra obtained from field and laboratory measurements using the
      temperature and emissivity separation algorithm.
AB  - Surface emissivities play an important role in thermal remote sensing, since
      knowledge of them is required to estimate land surface temperature with enough
      accuracy. They are also important in other environmental or geological studies.
      We show the results obtained for the emissivity spectra of different natural
      surfaces (water, green, and senescent vegetation) by applying the temperature and
      emissivity separation (TES) algorithm to ground-based measurements collected at
      the field with a multiband thermal radiometer. The results have been tested with
      data included in spectral libraries, and rms errors lower than 0.01 have been
      found, except for senescent vegetation. Two methods are also proposed to apply
      the TES algorithm to measurements achieved in the laboratory: (i) by heating the
      sample and (ii) using a box with reflective walls.

PMID- 16946790
TI  - Using shaded filter instruments for measurements of sky radiance: retrieval of
      the apparent sky-view factor from ultraviolet radiation measurements.
AB  - There is a growing need for sky radiometric measurements that encapsulate spatial
      as well as temporal variability. Since the advent of fast data acquisition
      systems in the 1980s, recent studies have utilized radiation filter instruments
      deployed in various sky-shading platforms. One cost effective method provides
      azimuthally averaged sky radiance distribution data at time scales down to
      fractions of a minute. Successful operation of this scheme requires knowledge of
      the apparent sky-view factor of the deployed sensor--an artifact of the
      instrument input optics, instrument filter design, and the instrument shading
      device employed. We provide a methodology for a determination of the sensor sky
      view factor by using the employed shading device and the sun as a light source.
      The effect of an incorrect determination of instrument sky-view factor is also
      analyzed in context of the measurements.

PMID- 16946791
TI  - Numerical analysis and experimental results of high-power Er/Pr:ZBLAN 2.7 microm
      fiber lasers with different pumping designs.
AB  - Gain factor and output performance of erbium-praseodymium codoped ZBLAN double
      clad fiber lasers at 2.7 microm with different pumping designs were calculated
      and analyzed. Single-end backward pumping with a highly reflective mirror butted
      against one fiber end and dual-end pumping with Fresnel reflections from both
      fiber ends were found to be the most efficient pumping designs. Ten-watt-level
      Er/Pr:ZBLAN fiber lasers proved to be achievable with recent diode laser and
      ZBLAN fiber technologies. Their corresponding optimum fiber lengths for different
      pumping configurations were determined. It was also found that fiber lasers with
      a flat evolution of gain factor can obtain the largest output power. Experimental
      results of 4 m and 12 m fiber lasers showed very good agreement with simulation
      results.

PMID- 16946792
TI  - Experimental study on an all gas-phase iodine laser using microwave discharge of
      Cl2/He as a Cl atoms source.
AB  - Microwave discharge of a Cl2/He mixture as a simple, clean and efficient Cl atom
      generator was used for an all gas-phase iodine laser study. Sufficient
      NCl(a1Delta) was produced through the reaction of HN3+2Cl-->NCl(a1Delta)+HCl+N2.
      The energy transfer reaction of I(2P3/2)+NCl(a1Delta)-->I(2P1/2)+NCl(X3Sigma) was
      observed. A population inversion was observed directly by using a 1315 nm tunable
      diode laser by scanning the entire line shape of the (3,4) hyperfine transition
      of iodine, and a small signal gain of 5x10(-5) cm-1 was obtained.

PMID- 16946793
TI  - Design of Stark-tuned far-infrared laser with circular hollow waveguide.
AB  - A novel design of a Stark-tuned far-infrared laser using a circular hollow
      dielectric waveguide is proposed, and its characteristics are studied.
      Supplementary electrodes are inserted inside the circular hollow dielectric tube
      to suppress charge accumulation while keeping field uniformity. In what is
      believed to be a new design, the mode property is found to be improved, and the
      angular dependency of the attenuation loss according to the beam polarization is
      estimated to be much smaller than that of the conventional rectangular hybrid
      waveguide design. In this new design, DeltaM=0 far-infrared (FIR) transition as
      well as DeltaM=+/-1 transition can be observed, and the power enhancement for the
      DeltaM=0 FIR transition is expected.

PMID- 16946794
TI  - Optical characteristics of femtosecond laser micromachined periodic structures in
      Si <100>.
AB  - A frequency doubled Ti:sapphire laser of 400 nm wavelength, 160 fs pulse width,
      and 1 kHz repetition rate, combined with a high resolution computer-controlled X
      Y stage, was used to direct write periodic structures on Si <100>. Laser pulses
      of approximately 130 nJ energy were focused using an objective lens of 0.65 NA.
      Laser micromachining yielded lines of 700 nm width and ablation depths of 600 nm.
      One- and two-dimensional periodic structures of 5 and 5x5 microm spacing were
      fabricated, and the structures were characterized by using optical and atomic
      force microscopy. The light diffraction characteristics of the periodic 1D and 2D
      patterns were examined. The diffraction properties of the 1D structures were
      highly dependent upon the light polarization orientation with respect to the
      micromachining direction.

PMID- 16946795
TI  - Wideband design of nonreciprocal phase shift magneto-optical isolators using
      phase adjustment in Mach-Zehnder interferometers.
AB  - A wideband design is proposed for nonreciprocal phase shift magneto-optical
      isolators based on Mach-Zehnder interferometers. The wavelength dependence of
      nonreciprocal phase difference between the backward waves propagating in two
      interferometer arms is compensated for by that of reciprocal phase difference.
      This is realized by introducing an appropriate phase bias in one of
      interferometer arms. Two design examples are presented with a backward loss of
      >30 dB in the wavelength range of 1.40-1.63 microm for a magnetic garnet
      waveguide isolator and of 1.485-1.630 microm for a Si-wire waveguide isolator.

PMID- 16946796
TI  - Excitation of waveguide modes in organic light-emitting diode structures by
      classical dipole oscillators.
AB  - Analytical techniques known in the literature are used to (i) identify all the
      planar waveguide modes in four top-emitting organic light-emitting diode (OLED)
      structures over the visible spectrum, and (ii) compute both TM and TE power
      spectra for classically radiating dipoles in the emissive layers of these OLED
      structures. Peaks in the computed power spectra are identified with the waveguide
      modes in the OLED devices, and areas associated with these peaks are used to
      estimate the excitation probability of the waveguide modes. In cases where
      ambiguities arise because of overlapping peaks, it is shown that computed power
      spectra can be approximated as sums of Lorentzian line shapes. It is found that
      for all four structures, the dipoles couple almost 80% of their radiant energy
      into TM modes with only about 20% going into TE modes. Furthermore, except for a
      narrow spectral band, the excited TM modes are primarily short-range surface
      plasmon polaritons. Excitations in the narrow spectral band correspond to TM and
      TE Fabry-Perot microcavity modes. Finally, the analysis shows that, in the
      absence of grating couplers, only light in the microcavity modes escapes into the
      air cover.

PMID- 16946797
TI  - Backscattering of light from disklike particles: is fine-scale structure or gross
      morphology more important?
AB  - The backscattering of light from disklike objects possessing periodic structures
      (e.g., resembling a wheel with spokes, hereafter called a pinwheel) or an object
      with a wavelength-sized deviation from a flat disk (e.g., a spherical cap) has
      been computed by using the discrete dipole approximation. The disks ranged in
      diameter from 1.5 to 2.7 microm with thicknesses from 0.04 to 0.15 microm. The
      goal of the study was to obtain some understanding of the differences between the
      backscattering of a collection of such objects in random orientation and a
      collection of randomly oriented homogeneous disks of the same size, i.e., the
      conditions under which the gross morphology (e.g., disklikeness) of these objects
      determines their backscattering. The computations for pinwheels showed that their
      backscattering cross sections were nearly identical to those of homogeneous disks
      of similar size (but with reduced effective refractive indices that are easily
      estimated) as long as the maximum separations between the spokes was less than
      one quarter of the wavelength. In this regime the backscattering is totally
      governed by the particle's gross morphology and effective index. For larger spoke
      separation, departures from a homogeneous disk are observed and manifest as
      significant increases (many times) in backscattering. In the case of spherical
      caps with the same projected area as the associated disk, the computations again
      show a complete similarity in their backscattering, and when the disks are
      sufficiently thin (with thickness divided by wavelength<0.15 to 0.25) there is
      very little difference between the backscattering of a cap and the associated
      disk.

PMID- 16946798
TI  - Bundled hollow optical fibers for transmission of high-peak-power Q-switched
      Nd:YAG laser pulses.
AB  - A hollow-fiber bundle was designed and used to deliver high-peak-power pulses
      from a Q-switched Nd:YAG laser. An 80 cm long bundle with a total diameter of 5.5
      mm was composed of 37 glass capillaries with bore diameters of 0.7 mm. Beam
      resizing optics with two lenses were used to couple the laser beam into the
      bundle. The measured coupling loss due to the limited aperture ratio of the
      bundle was 2.3 dB, and the transmission loss at wavelengths of 1064 and 532 nm
      was 0.3 dB. When an inert gas flowed through the bores of the capillaries, the
      maximum output pulse energy was 200 mJ, which was the limit of the laser used in
      the experiment. Hollow-fiber bundles withstand irradiation better than single
      hollow fibers and silica-glass optical fibers do. They are suitable for many
      dermatological applications because they can be used to irradiate a large area.

PMID- 16946799
TI  - Attachment and core relationship themes: wishes for autonomy and closeness in the
      narratives of securely and insecurely attached adults.
AB  - This study examines links between attachment states of mind and relationship
      schemas in a sample of 40 young adults, half of whom were hospitalized as
      adolescents for psychiatric treatment. Participants were interviewed about their
      closest relationships, and, using the Core Conflictual Relationship Theme method,
      their narratives about these relationships were analyzed for the relative
      frequency with which they expressed wishes for closeness and for autonomy in
      relation to others. Participants were also administered the Adult Attachment
      Interview and were classified with respect to security of attachment. Security of
      attachment was associated with the relative frequency with which participants
      expressed wishes for autonomy in their narratives about close relationships, even
      after accounting for current levels of psychological functioning and history of
      serious psychopathology in adolescence. Security of attachment was not associated
      with the relative frequency with which participants expressed wishes for
      closeness. The study suggests that core relational wishes for autonomy are linked
      specifically with subtypes of insecure attachment. These findings extend what is
      known about connections between the representation of early attachment
      relationships and the wishes and needs expressed in current relationships with
      significant others.

PMID- 16946801
TI  - Preventing sarcopenic obesity among breast cancer patients who receive adjuvant
      chemotherapy: results of a feasibility study.
AB  - PURPOSE: Weight gain is a common side effect of adjuvant chemotherapy for breast
      cancer - a side effect that decreases quality of life and also may decrease both
      disease-free and overall survival. This weight gain also is unique, since
      patients lose lean body mass while they gain weight. These body composition
      changes become apparent within six months of diagnosis. METHODS: We explored
      whether a clinic-based exercise program, which promoted a specialized program of
      strength training, aerobic activity and a healthful (</=20% fat; fruit, vegetable
      and calcium-rich) diet could prevent body composition change among Stage I/II
      premenopausal breast cancer patients who would receive adjuvant chemotherapy.
      Dual energy x-ray absorptiometry was used to assess body composition at both
      baseline and at six-month follow-up. Data from patients participating in the
      intervention (N=9) were compared to data from historic patient controls (N=36).
      RESULTS: Mean changes (SE) in body weight and composition at 6 month follow-up
      were as follows among historic patient controls and intervention participants,
      respectively: body weight +2.2(.4) kg vs. -2.0(1.3) kg (p=.02); % body fat
      +1.8(1.6)% vs. -1.3(1.2)% (p=.002); lean body mass -0.3(.01) kg vs. +0.1(1.5) kg
      (p=.80); and fat mass +2.0(.3) kg vs. -1.2(1.5) kg (p=.04). CONCLUSION: Data from
      this pilot study suggest that exercise/diet interventions may yield promise in
      preventing adverse chemotherapy-induced weight and body composition changes among
      young women who receive adjuvant chemotherapy for breast cancer, and that further
      study is needed. Since over half of the women approached for this intervention
      study refused on the basis of time and travel requirements, interventions that
      utilize home-based approaches may be necessary to reach greater numbers and a
      greater diversity of patients.

PMID- 16946802
TI  - Stress-buffering or stress-exacerbation? Social support and social undermining as
      moderators of the relationship between perceived stress and depressive symptoms
      among married people.
AB  - This prospective panel study examined social support and social undermining from
      the spouse as moderators of the relationship between perceived stress and
      depressive symptoms. Participants were 181 married people who completed
      questionnaires at two points in time. The interval between time 1 (T1) and time 2
      (T2) was approximately 6 weeks. Multiple regression analysis showed that T1
      perceived stress and T1 spouse undermining, but not T1 spouse support, predicted
      increases in depressive symptoms from T1 to T2. T1 spouse undermining, but not T1
      spouse support, moderated the association between T1 perceived stress and T2
      depressive symptoms. These findings supported a stress-exacerbation hypothesis
      for the effect of spouse undermining on the stress process. Discussion focuses on
      possible mechanisms for the stress-exacerbation effect.

PMID- 16946803
TI  - "World Psychiatry": an opportunity for psychiatrists of the world.

PMID- 16946804
TI  - Biological phenotypes and genetic research on schizophrenia.

PMID- 16946805
TI  - Evolutionary biology: a basic science for psychiatry.

PMID- 16946806
TI  - The sequential approach to relapse prevention in unipolar depression.

PMID- 16946807
TI  - Understanding the impact of stigma on people with mental illness.

PMID- 16946808
TI  - Strategies for reducing stigma toward persons with mental illness.

PMID- 16946809
TI  - From intuition- to evidence-based anti-stigma interventions.

PMID- 16946810
TI  - What else can we do to combat stigma?

PMID- 16946811
TI  - The power of stigma.

PMID- 16946813
TI  - The roots of stigmatization.

PMID- 16946812
TI  - What causes stigma?

PMID- 16946814
TI  - Fighting stigma: theory and practice.

PMID- 16946815
TI  - Integrating people who are stigmatized: the tetralogue model.

PMID- 16946816
TI  - Stigma is universal but experiences are local.

PMID- 16946817
TI  - Working together to modify prejudices.

PMID- 16946818
TI  - The WPA and the fight against stigma because of mental diseases.

PMID- 16946819
TI  - Mental health in Africa: the role of the WPA.

PMID- 16946820
TI  - The WPA International Guidelines for Diagnostic Assessment.

PMID- 16946821
TI  - Mental health resources in the world: results from Project Atlas of the WHO.

PMID- 16946822
TI  - The EPSILON Study - a study of care for people with schizophrenia in five
      European centres.

PMID- 16946823
TI  - BALANCE: a large simple trial of maintenance treatment for bipolar disorder.

PMID- 16946824
TI  - Families and mental health workers: the need for partnership.

PMID- 16946826
TI  - Creating a department of psychiatry in a developing country.

PMID- 16946825
TI  - Women's mental health in Tunisia.

PMID- 16946827
TI  - The scientific programme of the 12th World Congress of Psychiatry.

PMID- 16946828
TI  - New and forthcoming WPA books.

PMID- 16946829
TI  - News from the WPA secretariat.

PMID- 16946831
TI  - Scheduled to appear in forthcoming issues of "World Psychiatry".

PMID- 16946832
TI  - The strategy and policies of the WPA.

PMID- 16946833
TI  - Schizophrenic autism: clinical phenomenology and pathogenetic implications.

PMID- 16946835
TI  - The evolving epidemiology of bipolar disorder.

PMID- 16946834
TI  - Neurodevelopmental impairment, dopamine sensitisation, and social adversity in
      schizophrenia.

PMID- 16946837
TI  - Managing the psychiatric morbidity of disasters.

PMID- 16946836
TI  - Mental health services for victims of disasters.

PMID- 16946838
TI  - Special teams for medical/psychological intervention in disaster victims.

PMID- 16946839
TI  - Mental health services for victims of disasters in developing countries: a
      challenge and an opportunity.

PMID- 16946840
TI  - Mental health intervention and high-risk groups in disasters.

PMID- 16946841
TI  - Disaster mental health: lessons learned from the Hanshin Awaji earthquake.

PMID- 16946842
TI  - Disaster mental health care: the experience of Turkey.

PMID- 16946843
TI  - Behavioral consequences of disasters: a timely reminder.

PMID- 16946844
TI  - Mental health care for people with mental retardation: a global perspective.

PMID- 16946845
TI  - Psychophysiology in psychiatry: new perspectives in the study of mental
      disorders.

PMID- 16946846
TI  - From epidemiology to intervention for depressive disorders in the general
      population: the ODIN study.

PMID- 16946847
TI  - The UK700 trial of Intensive Case Management: an overview and discussion.

PMID- 16946848
TI  - Mental health of refugees: the case of Albania.

PMID- 16946849
TI  - Suicide and psychiatric diagnosis: a worldwide perspective.

PMID- 16946850
TI  - Usefulness and limitations of treatment guidelines in psychiatry.

PMID- 16946851
TI  - WPA educational programs.

PMID- 16946853
TI  - New WPA officers.

PMID- 16946852
TI  - News from WPA Sections.

PMID- 16946854
TI  - Partnership for mental health: the 12th World Congress of Psychiatry.

PMID- 16946855
TI  - Dysfunctional connectivity in schizophrenia.

PMID- 16946856
TI  - Attachment, information processing, and psychiatric disorder.

PMID- 16946857
TI  - The recognition and optimal management of early psychosis: an evidence-based
      reform.

PMID- 16946858
TI  - Balancing community-basedand hospital-based mental health care.

PMID- 16946859
TI  - Integration is as essential as balance.

PMID- 16946860
TI  - Deficiencies in community-based mental health care and possible remedies.

PMID- 16946861
TI  - Evaluating the feasibility of crisis homes: an application of the matrix model.

PMID- 16946862
TI  - Challenges of balanced care in Africa.

PMID- 16946863
TI  - The search for seamless care.

PMID- 16946864
TI  - Community-based vs. hospital-based mental health care: the case of Africa.

PMID- 16946865
TI  - Mental health systems: proposals beyond evidence-based mental health?

PMID- 16946866
TI  - Developing models of balanced mental health care: the case of Pakistan.

PMID- 16946867
TI  - Dis-sociality: the phenomenological approach to social dysfunction in
      schizophrenia.

PMID- 16946868
TI  - Measurement of some novel concepts in psychiatry.

PMID- 16946869
TI  - Exploring boundaries of schizophrenia: a comparison of ICD-10 with other
      diagnostic systems in first-admitted patients.

PMID- 16946870
TI  - Psychotherapy and antidepressant treatment of depression: evidence for similar
      neurobiological mechanisms.

PMID- 16946871
TI  - Mental health and mental health care in Asia.

PMID- 16946872
TI  - Mental health of refugees: the case of Azerbaijan.

PMID- 16946873
TI  - Bioethics and psychiatry: a challenging future.

PMID- 16946874
TI  - The Declaration of Madrid and its implementation.

PMID- 16946875
TI  - The work of the WPA Committee to Review the Abuse of Psychiatry.

PMID- 16946876
TI  - News from the WPA Secretariat.

PMID- 16946877
TI  - WPA proposal regarding the escalation of violence in the Middle East.

PMID- 16946879
TI  - The future of psychotherapies for mood disorders.

PMID- 16946878
TI  - The future of antidepressant pharmacotherapy.

PMID- 16946880
TI  - Supporting governments to adopt mental health policies.

PMID- 16946883
TI  - The cup is both half empty and half full.

PMID- 16946882
TI  - Does family psychoeducation have a future?

PMID- 16946884
TI  - Issues in the dissemination of family intervention for psychosis.

PMID- 16946881
TI  - Family interventions for mental disorders: efficacy and effectiveness.

PMID- 16946885
TI  - Issues for further refinement of family interventions in schizophrenia.

PMID- 16946886
TI  - Family interventions for serious mental illness: translating research to
      practice.

PMID- 16946887
TI  - Family interventions and empowerment as an approach to enhance mental health
      resources in developing countries.

PMID- 16946888
TI  - Broadening the international base for the development of an integrated diagnostic
      system in psychiatry.

PMID- 16946889
TI  - Personality disorder in psychiatric practice.

PMID- 16946890
TI  - The Edinburgh High Risk Study: current status and future prospects.

PMID- 16946891
TI  - Acute stress reaction among victims of the 1999 Athens earthquake: help seekers'
      profile.

PMID- 16946892
TI  - Mental health and mental health care in Latin America.

PMID- 16946893
TI  - Recent advances in graduate psychiatric training.

PMID- 16946894
TI  - The 12th world congress of psychiatry.

PMID- 16946895
TI  - WPA publications: recent developments and future plans.

PMID- 16946896
TI  - WPA strives to disseminate relevant psychiatric knowledge via scientific
      meetings.

PMID- 16946897
TI  - The Declaration of Madrid and its implementation. An update.

PMID- 16946898
TI  - Bipolar disorder and schizophrenia: not so distant relatives?
AB  - Bipolar disorder (BPD) and schizophrenia (SZ) may have some susceptibility genes
      in common, despite the fact that current nosology separates them into non
      overlapping categories. The evidence for shared genetic factors includes
      epidemiologic characteristics, family studies and overlap in confirmed linkages.
      Review of these data indicates that there are five genomic regions which may
      represent shared genetic susceptibility of BPD and SZ. As the genes underlying
      these confirmed linkages are identified, the current nosology must be changed to
      reflect the new knowledge concerning the shared etiologies of BPD and SZ.

PMID- 16946899
TI  - Psychoanalysis today.
AB  - The paper discusses the precarious position of psychoanalysis, a therapeutic
      approach which historically has defined itself by freedom from constraint and
      counted treatment length not in terms of number of sessions but in terms of
      years, in today's era of empirically validated treatments and brief structured
      interventions. The evidence that exists for the effectiveness of psychoanalysis
      as a treatment for psychological disorder is reviewed. The evidence base is
      significant and growing, but less than might meet criteria for an empirically
      based therapy. The author goes on to argue that the absence of evidence may be
      symptomatic of the epistemic difficulties that psychoanalysis faces in the
      context of 21st century psychiatry, and examines some of the philosophical
      problems faced by psychoanalysis as a model of the mind. Finally some changes
      necessary in order to ensure a future for psychoanalysis and psychoanalytic
      therapies within psychiatry are suggested.

PMID- 16946900
TI  - The future of pharmacotherapy for schizophrenia.
AB  - Although enormous progress has been made in the treatment of schizophrenia, and
      the use of existing pharmacologic agents can have a dramatic effect on the short-
      and long-term management of the disorder, enormous challenges and unmet needs
      continue to exist. Despite the introduction of a second generation of
      antipsychotic medications, many patients continue to derive inadequate benefits
      from available agents. Negative symptoms and cognitive dysfunction, and
      decrements in psychosocial and vocational functioning, often continue to persist
      despite our best available treatments. Medication adherence remains a constant
      challenge and has not been dramatically improved by the new-generation
      antipsychotic drugs. Since all currently marketed antipsychotic agents possess
      some degree of dopamine antagonist effects, the role of other neurotransmitters
      in the primary antipsychotic activity remains largely unclear. It is possible
      that different domains of disease effects might benefit from different specific
      classes of medications, yet research in this area is not highly developed. The
      promise of further discoveries in genetics leading to new treatment targets and
      better predictors of treatment response (both therapeutic and adverse) is
      enormously exciting, but these developments will require years of additional
      research. The field must balance the need to make the most informed and thorough
      use of available agents with a sense of both excitement and patience as we work
      toward other approaches.

PMID- 16946901
TI  - Psychiatry and the general hospital in an age of uncertainty.
AB  - General hospitals have had an illustrious role in the evolution of psychiatry.
      They have provided a rich soil for the growth of inpatient psychiatric units,
      consultation-liaison psychiatry, psychosomatic medicine, med-psych units,
      outpatient psychiatric clinics, emergency services and a whole spectrum of
      resources for the communities in which they dwell. In some respects, whether
      attached to universities or not, they have functioned as small colleges for the
      education and training of scores of health professionals. In the setting of the
      general hospital, psychiatry has had opportunities to become remedicalized and
      integrated into the mainstream of medicine. However, recent trends in health care
      run the risk of jeopardizing these accomplishments. Managed care has had a
      profound impact on the way psychiatry is practiced, taught, and reimbursed.
      Concerns about cost-containment have raised questions about whether the general
      hospital will remain the best and most economical setting for psychiatric
      services. If the primacy of the patient is lost, psychiatry's role in the general
      hospital will be uncertain. The need to safeguard psychiatry's achievements must
      be a worldwide endeavor.

PMID- 16946902
TI  - Consultation-liaison psychiatry worldwide.

PMID- 16946903
TI  - An international perspective on consultation-liaison psychiatry and the general
      hospital.

PMID- 16946904
TI  - The future of consultation-liaison psychiatry: prosper or perish?

PMID- 16946905
TI  - Psychiatry, psychosomatic medicine and the general hospital in Germany.

PMID- 16946906
TI  - Ten years behind 'an age of uncertainty'.

PMID- 16946908
TI  - General hospital psychiatry: a new sub-specialty?

PMID- 16946907
TI  - From consultation to integrated health risk assessment.

PMID- 16946909
TI  - Importance of general hospital in the development of mental health care.

PMID- 16946910
TI  - General hospital psychiatry: uncertainty starting from its name.

PMID- 16946912
TI  - General hospital psychiatry: the Italian experience.

PMID- 16946911
TI  - The worldwide prevalence of ADHD: is it an American condition?
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder that
      affects up to 1 in 20 children in the USA. The predominance of American research
      into this disorder over the past 40 years has led to the impression that ADHD is
      largely an American disorder and is much less prevalent elsewhere. This
      impression was reinforced by the perception that ADHD may stem from social and
      cultural factors that are most common in American society. However, another
      school of thought suggested that ADHD is a behavioral disorder common to children
      of many different races and societies worldwide, but that is not recognized by
      the medical community, perhaps due to confusion regarding its diagnosis and/or
      misconceptions regarding its adverse impact on children, their families, and
      society as a whole. In this article we present the available data, with a view to
      determining the worldwide prevalence of ADHD. A total of 50 studies were
      identified from a MEDLINE search for the terms ADHD, ADD, HKD, or attention
      deficit/hyperactivity disorder and prevalence combined, for the years 1982 to
      2001. 20 were studies in US populations and 30 were in non-US populations.
      Analysis of these studies suggests that the prevalence of ADHD is at least as
      high in many non-US children as in US children, with the highest prevalence rates
      being seen when using DSM-IV diagnoses. Recognition that ADHD is not purely an
      American disorder and that the prevalence of this behavioral disorder in many
      countries is in the same range as that in the USA will have important
      implications for the psychiatric care of children.

PMID- 16946913
TI  - Adapting group interpersonal psychotherapy for a developing country: experience
      in rural Uganda.
AB  - The current prevalence of depressive symptoms in Southwest Uganda, an area
      greatly affected by the HIV epidemic, has been shown to be as high as 21%.
      Traditional healers have expressed inability to treat these symptoms. The lack of
      physicians and high cost of medication make the use of antidepressants
      unfeasible. Therefore, an evidence-based psychotherapy was considered a
      reasonable treatment option by a team of health researchers familiar with the
      local culture, who designed a randomized controlled clinical trial. Interpersonal
      psychotherapy in a group format (IPT-G) was selected because it was time limited,
      was described in a manual, and had evidence of efficacy from clinical trials.
      Moreover, its focus on interpersonal triggers of depression was considered
      compatible with the culture. This paper describes the process of adapting the
      psychotherapy manual and the training of the group leaders who undertook the
      first psychotherapy clinical trial in Africa.

PMID- 16946914
TI  - Violence and mental illness: an overview.
AB  - THIS PAPER EVALUATES THE RELATIONSHIP OF MENTAL ILLNESS AND VIOLENCE BY ASKING
      THREE QUESTIONS: Are the mentally ill violent? Are the mentally ill at increased
      risk of violence? Are the public at risk? Mental disorders are neither necessary
      nor sufficient causes of violence. Major determinants of violence continue to be
      socio-demographic and economic factors. Substance abuse is a major determinant of
      violence and this is true whether it occurs in the context of a concurrent mental
      illness or not. Therefore, early identification and treatment of substance abuse
      problems, and greater attention to the diagnosis and management of concurrent
      substance abuse disorders among seriously mentally ill, may be potential violence
      prevention strategies. Members of the public exaggerate both the strength of the
      association between mental illness and violence and their own personal risk.
      Finally, too little is known about the social contextual determinants of
      violence, but research supports the view the mentally ill are more often victims
      than perpetrators of violence.

PMID- 16946915
TI  - Rethinking mental health: a European WHO perspective.
AB  - In spite of recent clinical and research advances, an increased burden of
      mortality and morbidity related to stress and mental ill health can be noted,
      especially in European societies and populations undergoing stressful transitions
      and dramatic changes. A societal syndrome, consisting of depression, suicide,
      abuse, risk-taking and violent behaviour as well as vascular morbidity and
      mortality, can be observed, reflecting individual psychopathology related to
      disturbances of the serotonin metabolism as one of the oldest, most basic
      cerebral instruments of mankind to survive, to socialize, to cope with stress and
      danger. In a time where mental health professionals look for new and challenging
      identities, they have a tendency to abdicate from social psychiatric and public
      health activities in favour of more prestigious positions in brain research,
      genetics or advanced psychotherapy. A redefinition, reconceptualization and
      renaissance of social psychiatry seems timely and necessary, responding to the
      burden, advances and possibilities related to mental health we find today. It
      should proceed from the reductionism which often has characterized earlier
      psychosocial and social psychiatric approaches, utilize modern knowledge about
      neuroplasticity, psychoimmunology, neuropsychology and neurophilosophy, reflect
      the interaction between environment and structure, nature and nurture, and
      integrate different areas of knowledge in a holistic public mental health
      approach. Political decisions and societal solutions can be more or less in line
      with basic human preconditions. Consequences of failure to respect this already
      can be seen. A new awareness and responsibility-taking with regard to basic human
      ethological, physiological, psychological and existential conditions is needed
      and has to be concretized in innovative public mental health approaches.

PMID- 16946916
TI  - The WPA International Congress "Treatments in Psychiatry: An Update".

PMID- 16946917
TI  - The Presidential WPA Program on Child Mental Health.

PMID- 16946918
TI  - Personality disorder diagnosis.
AB  - Every person has a characteristic manner of thinking, feeling, and relating to
      others. Some of these personality traits can be so dysfunctional as to warrant a
      diagnosis of personality disorder. The World Health Organization's International
      Classification of Diseases (ICD- 10) includes ten personality disorder diagnoses.
      Three issues of particular importance for the diagnosis of personality disorders
      are their differentiation from other mental disorders, from general personality
      functioning, and from each other. Each of these issues is discussed in turn, and
      it is suggested that personality disorders are more accurately and effectively
      diagnosed as maladaptive variants of common personality traits.

PMID- 16946919
TI  - The underlying neurobiology of bipolar disorder.
AB  - Clinical studies over the past decades have attempted to uncover the biological
      factors mediating the pathophysiology of bipolar disorder (BD) utilizing a
      variety of biochemical and neuroendocrine strategies. Indeed, assessments of
      cerebrospinal fluid chemistry, neuroendocrine responses to pharmacological
      challenge, and neuroreceptor and transporter binding have demonstrated a number
      of abnormalities in the amine neurotransmitter systems in this disorder. However,
      recent studies have also implicated critical signal transduction pathways as
      being integral to the pathophysiology and treatment of BD, in addition to a
      growing body of data suggesting that impairments of neuroplasticity and cellular
      resilience may also underlie the pathophysiology of the disorder. It is thus
      noteworthy that mood stabilizers and antidepressants indirectly regulate a number
      of factors involved in cell survival pathways - including MAP kinases, CREB, BDNF
      and bcl-2 protein - and may thus bring about some of their delayed long-term
      beneficial effects via underappreciated neurotrophic effects.

PMID- 16946920
TI  - The future of psychological therapies for psychosis.
AB  - The need for psychological therapies for psychosis is increasingly recognised. In
      recent years, two psychological approaches, cognitive behavioural therapy (CBT)
      and family interventions (FI), have emerged from among a range of psychological
      approaches as effective therapies with the strongest evidence base. The
      theoretical basis of these approaches, within a broader biopsychosocial stress
      vulnerability framework, is described. The evidence of effectiveness, drawn from
      the results of recent systematic reviews of CBT and FI, is summarised. CBT is
      found to reduce symptoms and FI to reduce relapse, with some evidence of
      improvement in other outcomes for both approaches. Future directions for these
      therapies are considered, with particular emphasis on their role in early
      intervention services and relapse prevention. Promising newer applications of
      these approaches are also discussed, for example in work with people with a dual
      diagnosis of psychosis and substance misuse disorder. Finally, training and
      dissemination issues are addressed. It is emphasised that the integration of
      psychological therapies within comprehensive service provision is important.

PMID- 16946921
TI  - Psychiatry and primary care.
AB  - There is now almost universal recognition that primary care is the place where
      most mentally distressed people first present for help. However, the pace at
      which the health system has adapted to this reality varies greatly from country
      to country, depending on the amount of resource devoted to mental illness
      services, the way in which primary care physicians have organized their practice,
      and the inertia of the system. Here we present several models from developed and
      developing countries and address briefly the issue of training of health workers.

PMID- 16946922
TI  - Improving the filter between primary and secondary care for mental disorders.

PMID- 16946923
TI  - Can medical practice adapt to a changed world?

PMID- 16946924
TI  - Five decades of research on psychiatric morbidity in primary care.

PMID- 16946925
TI  - Integrating depression treatment into primary care for common medical illnesses.

PMID- 16946926
TI  - The burden of depression in primary care.

PMID- 16946927
TI  - Managing the global burden of depression: lessons from the developing world.

PMID- 16946928
TI  - Mental health services in primary care in 'developing' countries.

PMID- 16946929
TI  - Mental health and primary care in Nigeria.

PMID- 16946930
TI  - Probing cortical dopamine function in schizophrenia: what can D1 receptors tell
      us?
AB  - Schizophrenia is characterized by positive symptoms, negative symptoms and
      cognitive impairment. Positive symptoms may be related to excessive dopamine (DA)
      function, as suggested by the common antidopaminergic properties of antipsychotic
      medications, which are most effective at treating positive symptoms. Negative
      symptoms and impairment in higher cognitive functions are thought to be related
      to a dysfunction of the dorsolateral prefrontal cortex (DLPFC), possibly related
      to inappropriate stimulation of D1 receptors. In the last few years we have
      clearly demonstrated excess subcortical DA transmission and now have indirect
      evidence for cortical dopamine deficit. We studied 16 drug free patients with
      schizophrenia (7 drug naive and 9 previously treated) and 16 matched controls,
      using positron emission tomography (PET) and [(11)C]NNC 112, a novel radiotracer
      for PET imaging of the D1 receptor, and the n-back task, a test of working
      memory. We observed a significant upregulation in D1 binding in the DLPFC in
      patients with schizophrenia compared to controls. This increase was present in
      both drug naive and previously treated patients and was regionally selective.
      Furthermore, the increase was correlated with poor performance on the n-back task
      (r(2)=0.45, p=0.004). This upregulation of D1 receptors might be secondary to a
      sustained deficit in prefrontal DA function, as postmortem studies revealed
      deficits in DA innervation in the prefrontal cortex in schizophrenia.

PMID- 16946931
TI  - Symptom dimensions and outcome in schizophrenia.
AB  - Since Kraepelin, outcome has been one of the most frequently used criteria for
      testing the validity of diagnosis in psychiatry. Factor analytic methods have
      showed, however, that the symptomatology of psychiatric patients can be divided
      into symptom dimensions, which also correlate with outcome. The aim of the
      present study was to explore how diagnostic sub-categories and symptom dimensions
      correlate with outcome in first-episode and chronic patients with schizophrenia.
      In samples of first-episode schizophrenia patients (n=156) and chronic
      schizophrenia patients (n=1571), symptom variables were factored and the five
      symptom dimensions obtained were correlated with outcome variables. In both
      samples, symptom dimensions were more powerful in explaining variance of outcome
      than categorical sub-diagnoses. Thus, a dimensional approach seems to be valuable
      not only in describing the illness picture, but also in predicting outcome in
      schizophrenia.

PMID- 16946932
TI  - Integration initiatives for forensic services.
AB  - Poorly implemented mental health reform policies are often given as reasons for
      the growth in demands for forensic psychiatric services and the steady increase
      of mental patients in prison systems. However, in this paper, additional reasons
      are advanced to explain the growth of forensic psychiatry, such as an expansion
      in the types of "psychiatric defences" in courts of law; public concerns about
      violent behaviour attributed to the mentally ill; the community management of
      paraphilias, especially pedophilia; the development of risk assessment
      methodologies and the halo of super-specialization. The net result of these
      developments is that patients who receive a label of "forensic" enter into a
      mental health ghetto with little connectivity or integration with the general
      mental health system. The forensic label increases the stigma and decreases
      opportunities for reintegration and full social recovery. The paper provides
      guidelines to reverse these trends.

PMID- 16946934
TI  - The WPA website.

PMID- 16946935
TI  - News from the WPA Secretariat.

PMID- 16946933
TI  - Chronic cognitive impairment in users of 'ecstasy' and cannabis.
AB  - MDMA use is commonly accompanied by use of other substances, most notably
      cannabis. Both MDMA and cannabis have probable effects on cognition. This paper
      reviews research into long-term effects on cognition which are likely to
      represent neurotoxicity. Research is hampered by numerous confounds and
      methodological difficulties. With recent cannabis use there is both an acute and
      a residual effect on cognition, making it important to have a significant
      abstinence period from cannabis when studying effects of MDMA in recreational
      users of both substances. It would appear that MDMA does indeed have subtle long
      term effects on complex memory and executive functions that are independent of
      cannabis and may remain with abstention. This is consistent with evidence of
      disruption of the serotonin system in animal and human studies. Chronic effects
      on cognition due to cannabis are less consistently demonstrated, but more
      sensitive tests including electrophysiological measures have revealed long-term
      deficits in attention.

PMID- 16946936
TI  - Institutional consolidation and global impact: towards a psychiatry for the
      person.

PMID- 16946937
TI  - Returning the debt: how rich countries can invest in mental health capacity in
      developing countries.

PMID- 16946938
TI  - The science of well-being: an integrated approach to mental health and its
      disorders.
AB  - Psychiatry has failed to improve the average levels of happiness and well-being
      in the general population, despite vast expenditures on psychotropic drugs and
      psychotherapy manuals. The practical failure of psychiatry to improve well-being
      is the result of an excessive focus on stigmatizing aspects of mental disorders
      and the neglect of methods to enhance positive emotions, character development,
      life satisfaction, and spirituality. In this paper, a simple and practical
      approach to well-being is described by integrating biological, psychological,
      social, and spiritual methods for enhancing mental health. Evidence is presented
      showing that people can be helped to develop their character and happiness by a
      catalytic sequence of practical clinical methods. People can learn to flourish
      and to be more selfdirected by becoming more calm, accepting their limitations,
      and letting go of their fears and conflicts. People can learn to be more
      cooperative by increasing in mindfulness and working in the service of others. In
      addition, people can learn to be more self-transcendent by growing in self
      awareness of the perspectives that lead to beliefs and assumptions about life
      which produce negative emotions and limit the experience of positive emotions.
      The personality traits of self-directedness, cooperativeness, and self
      transcendence are each essential for well-being. They can be reliably measured
      using the Temperament and Character Inventory. A psychoeducational program for
      wellbeing has been developed, called "The happy life: voyages to well-being". It
      is a multi-stage universal-style intervention by which anyone who wants to be
      happier and healthier can do so through self-help and/or professional therapy.

PMID- 16946939
TI  - The social brain hypothesis of schizophrenia.
AB  - The social brain hypothesis is a useful heuristic for understanding
      schizophrenia. It focuses attention on the core Bleulerian concept of autistic
      alienation and is consistent with well-replicated findings of social brain
      dysfunction in schizophrenia as well as contemporary theories of human cognitive
      and brain evolution. The contributions of Heidegger, Merleau-Ponty and
      Wittgenstein allow us to arrive at a new "philosophy of interpersonal
      relatedness", which better reflects the "embodied mind" and signifies the end of
      Cartesian dualistic thinking. In this paper I review the evolution, development
      and neurobiology of the social brain - the anatomical and functional substrate
      for adaptive social behaviour and cognition. Functional imaging identifies fronto
      temporal and fronto-parietal cortical networks as comprising the social brain,
      while the discovery of "mirror neurons" provides an understanding of social
      cognition at a cellular level. Patients with schizophrenia display abnormalities
      in a wide range of social cognition tasks such as emotion recognition, theory of
      mind and affective responsiveness. Furthermore, recent research indicates that
      schizophrenia is a disorder of functional and structural connectivity of social
      brain networks. These findings lend support to the claim that schizophrenia
      represents a costly by-product of social brain evolution in Homo sapiens.
      Individuals with this disorder find themselves seriously disadvantaged in the
      social arena and vulnerable to the stresses of their complex social environments.
      This state of "disembodiment" and interpersonal alienation is the core phenomenon
      of schizophrenia and the root cause of intolerable suffering in the lives of
      those affected.

PMID- 16946940
TI  - Recent developments in the theory of dissociation.
AB  - Although the construct of dissociation was introduced into psychiatry at the end
      of the 19th century by Pierre Janet, the term still lacks a coherent
      conceptualization, which is partially reflected by differences in the
      classification of dissociative and conversion disorders in ICD-10 and DSM-IV.
      Given the clinical significance of dissociative psychopathology in numerous
      clinical conditions, it is very valuable that various efforts have been made to
      refine and to specify current conceptualizations in recent years. The most
      promising and convincing approaches converge in subdividing dissociation into
      qualitatively different types, i.e. pathological versus non-pathological
      dissociation, and "detachment" versus "compartmentalization". We review these
      concepts and discuss their scientific and clinical potential as well as their
      limitations.

PMID- 16946941
TI  - Forensic psychiatry: contemporary scope, challenges and controversies.
AB  - Forensic psychiatry is the branch of psychiatry that deals with issues arising in
      the interface between psychiatry and the law, and with the flow of mentally
      disordered offenders along a continuum of social systems. Modern forensic
      psychiatry has benefited from four key developments: the evolution in the
      understanding and appreciation of the relationship between mental illness and
      criminality; the evolution of the legal tests to define legal insanity; the new
      methodologies for the treatment of mental conditions providing alternatives to
      custodial care; and the changes in attitudes and perceptions of mental illness
      among the public. This paper reviews the current scope of forensic psychiatry and
      the ethical dilemmas that this subspecialty is facing worldwide.

PMID- 16946942
TI  - Forensic psychiatry: a developing subspecialty.

PMID- 16946943
TI  - The ethical implications of forensic psychiatry practice.

PMID- 16946944
TI  - Forensic psychiatry in dubious ascent.

PMID- 16946945
TI  - Psychiatry and torture.

PMID- 16946946
TI  - Crime and mental illness: it is time to take action.

PMID- 16946947
TI  - Forensic psychiatry today: a Latin American view.

PMID- 16946948
TI  - Forensic psychiatry: the African experience.

PMID- 16946950
TI  - Forensic psychiatric practice: worldwide similarities and differences.

PMID- 16946949
TI  - Exploring evolving concepts and challenges in forensic psychiatry.

PMID- 16946951
TI  - Treatment of patients with first-episode psychosis: two-year outcome data from
      the Danish National Schizophrenia Project.
AB  - First episode psychosis interventions have been in focus in the last two decades
      in an attempt to improve the course and outcome of schizophrenic disorders. The
      Danish National Schizophrenia Project began in 1997 its intake of patients, aged
      16-35, with a first psychotic episode of a schizophrenic spectrum disorder,
      diagnosed by ICD-10 (F20-29). The study was carried out as a prospective,
      longitudinal, multicentre investigation, encompassing 16 centres, spread all over
      the country. The sample consists of 562 patients consecutively diagnosed during
      two years. Patients were treated with "supportive psychodynamic psychotherapy as
      a supplement to treatment as usual", "integrated, assertive, psychosocial and
      educational treatment programme", or "treatment as usual". Data on symptoms and
      social function and sociodemographic data were obtained at inclusion, and at year
      1 and 2. The three sub-cohorts did not differ at baseline. After one year, the
      total sample of patients improved significantly concerning symptoms and social
      function. The significance of the improvement remained after two years. After one
      year, patients in the two intervention groups improved more concerning symptoms
      and social function than patients in the treatment-as-usual group. Improvement in
      the intervention groups continued into the second year. Patients receiving
      integrated assertive treatment faired better than those being treated with the
      less intensive method of supportive psychodynamic psychotherapy, and the latter
      group improved more than the treatment-as-usual group.

PMID- 16946952
TI  - Do beliefs about causation influence attitudes to mental illness?
AB  - Studies indicate that stigmatizing attitudes to mental illness are rampant in the
      community worldwide. It is unclear whether views about the causation of mental
      disorders identify persons with more negative attitudes. Using data collected as
      part of a community study of knowledge of and attitudes to mental illness in
      Nigeria, we examined the relationships between views about causation and
      attitudes. Persons holding exclusively biopsychosocial views of causation were
      not different from those holding exclusively religious-magical views in regard to
      socio-demographic attributes, and the two groups were not very dissimilar when
      general knowledge of the nature of mental illness was compared. However,
      religious-magical views of causation were more associated with negative and
      stigmatizing attitudes to the mentally ill. Findings demonstrate the challenge of
      developing and delivering an educational program to change public attitudes to
      mental illness.

PMID- 16946953
TI  - Palestinian mothers' perceptions of child mental health problems and services.
AB  - The aim of this study was to explore Palestinian mothers' perceptions of child
      mental health problems and their understanding of their causes; to determine
      Palestinian mothers' awareness of existing services and sources of help and
      support; to identify professionals in the community whom Palestinian mothers
      would consult if their child had mental health problems; and to establish their
      views on ways of increasing awareness of child mental health issues and services.
      Checklists exploring the above issues were completed by 249 Palestinian mothers
      living in refugee camps in the Gaza Strip. Palestinian mothers equally perceived
      emotional, behavioural and psychotic symptoms as suggestive of mental ill health
      in childhood. Mothers perceived multiple causes of child mental health problems,
      including family problems, parental psychiatric illness and social adversity. A
      substantial proportion (42.6%) had knowledge of local child mental health care
      services. Overall, mothers preferred Western over traditional types of treatment,
      and were keen to increase mental health awareness within their society. Despite a
      different cultural tradition, Palestinian mothers appear open to a range of
      services and interventions for child mental health problems. As in other non
      Western societies, child mental health service provision should be integrated
      with existing primary health care, schools, and community structures.

PMID- 16946954
TI  - Challenges for psychiatry: delivering the Mental Health Declaration for Europe.
AB  - Mental health care is in the process of transformation across the European
      Region, due to a combination of recognition of disease burden, poor treatment
      conditions and demand from clinicians and the public. This transformation affects
      the scope of mental health, increasingly including promotion and prevention, and
      the structure and process of care, shifting to community based delivery. Many
      psychiatrists are in leadership positions, able to influence policies and
      strategies. But their work is also seriously affected by the consequences of
      these policies. New roles and responsibilities of all members of a multi
      disciplinary team need to be planned, and education and training have to be
      designed to prepare professionals to deal with expectations and demands.
      Psychiatrists face major challenges, since their complex roles are affected in
      multiple ways by the psychiatric and general health system. Some of these
      challenges can be addressed by the psychiatric profession and their partners,
      including patient and family organizations; others require wide ranging changes
      in attitude and system design.

PMID- 16946955
TI  - Culture and mental health of women in South-East Asia.
AB  - This article reviews the impact of cultural factors on mental health of South
      Asian women. Marked gender discrimination in South Asia has led to second class
      status of women in society. Their mobility, work, self-esteem and self-image, in
      fact their worth and identity, seem to depend upon the male members of a
      patriarchal society. Women's lack of empowerment and both financial and emotional
      dependence have restricted their self-expression and choices in life. This, along
      with family, social and work pressures, has a definite impact on women's mental
      health.

PMID- 16946957
TI  - Triennial General Survey of WPA activity (2002-2005).

PMID- 16946956
TI  - Letter to the editor.

PMID- 16946958
TI  - WPA Scientific Meetings: the link between sciences and quality of care.

PMID- 16946959
TI  - WPA International Congress 2007 (Melbourne, Australia, November 28-December 2).

PMID- 16946961
TI  - [In Process Citation]

PMID- 16946962
TI  - [Hypothesis on suicidal behavior as interpersonal communication.].
AB  - Traditionnaly, suicidal behavior has been analysed through its individual and
      intrapsychic components and by its links with economic and social factors. To
      consider suicide as a message to the environment, then by highlighting its
      communicationnal aspect, is a new trend in the field. In fact, suicide often has
      a profound impact on the personal environment of the suicidal person. We
      therefore set forth the following hypothesis : suicide myths and tabous might be
      a social rationalization and defense mechanism against the violent impact of
      suicidal behavior. This paper explores the communication view point of suicidal
      behavior which interestingly open up new possibilities in the research and
      intervention on suicide.

PMID- 16946963
TI  - [Notes on a definition for alternatives practices and therapies in Quebec.].
AB  - The phenomenon of non-traditional therapies is firstly analyzed within the
      context of an increasing number of approaches in the therapeutic field in Quebec
      and the Western hemisphere and of the development of health care alternatives.
      The growth and diversity of alternative therapies legitimizes the need to
      establish an operational definition of this phenomenon, which is the framework of
      this article.

PMID- 16946964
TI  - [Assesment of a satellite clinic : a five-year experience of a pedopsychiatric
      team in a disadvantaged area.].
AB  - Having worked closely for more than ten years with a team of child psychiatrists
      that defines itself as community-oriented, I attempt to describe the process by
      which this team became established in its designated territory. My aim is to
      provide an overview spanning the five years during which a "satellite clinic"
      established itself in a low-income district. I proceed by drawing a profile of
      the neighboring population and that which consults in particular, of agencies
      that refer and their motives for referral, as well as of our ways of responding
      to their requests. I also examine the collaboration with the various
      organizations in the district and what this entails with regard to hopes, doubts
      and conflict. Although being located within the designated territory had an
      overall positive impact on our work and our objective to prevent and detect
      anomalies, it has not necessarily been helpful in establishing better links with
      neighboring "support" organizations.

PMID- 16946965
TI  - [Reflection on university training in psychiatric nursing.].
AB  - This article focuses on present-day training in the field of psychiatric nursing
      at the undergraduate level. Following the author's definition of a competent
      psychiatric nurse, she then offers suggestions and traces the difficulties
      encountered by the professor to develop three essential qualities in such a
      student: a humanist approach towards the client; true concern for the client
      experiencing mental health problems; and the development of personal qualities
      and aptitudes that enable the student to establish, maintain and successfully
      carry out a supportive relationship with the client. The author finally insists
      on the fact that, as in all disciplines, we must improve the standards for
      training students. However, her emphasis lies mostly on the need to restore the
      care and attention a nurse-client relationship deserves.

PMID- 16946966
TI  - [The mirror broke : Oedipe has aged, Beginning of a reflection on aging and
      otherness.].
AB  - The "mirror phase" is characterized by a child's recognition of his own image in
      the mirror and simultaneous perception of approval by the adult, whose reflection
      is equally discovered. In contrast to this phase, we identify an experience that
      takes place in old age: the experience referred to in this article as the
      <<shattered mirror>>, which occurs when the image reflected by the mirror no
      longer matches the expectations of the subject. This experience raises doubts
      concerning non only the relation of the subject with himself, but also with the
      other, who, ever since the "mirror phase", has supported the subject's identity.
      Encountering alterity, the process of discovering one's self as different and of
      confronting an other with whom similarities no longer hold true, is the crux of
      the "shattered mirror' ' experience and the basis for uprooting narcissist
      complacency. The dynamics of alterity therefore favour revealment (illustrated by
      the tragedy of "Oedipe a Colone", while the outcome of the "shattered mirror"
      experience ranges between distress and reduced alienation.

PMID- 16946967
TI  - [Community tolerance of the mentally ill.].
AB  - This article is divided into three parts. First of all, the author examines our
      level of tolerance concerning mental patients from a historic perspective and
      defines the issue. Secondly, the author identifies five variables to explain the
      idea of tolerance: ethnic origin, social class, sex, age and urban-rural milieu.
      Thirdly, he presents two case studies, carried out in Annonciation and Montreal,
      that show a shift towards a more positive attitude with regard to mental
      patients.

PMID- 16946968
TI  - [Seeking refuge in the community.].
AB  - One of the many objectives of psychiatrie deinstitutionaliza-tion is to try to
      ensure that individuals who receive treatment reintegrate their community. The
      author points out that, for a certain category of young people undergoing
      treatment, such an objective requires a much broader approach involving more than
      psychiatric intervention alone; an increasing proportion of young people are left
      without community support and using prison as their drop-in centre. The situation
      is examined from the points of view of institutional practice and the life
      experience of subjects. The author sheds light on another step of psychiatric
      deinstitutionalization, namely social deinstitutionalization of a community's
      acceptance, support and accompaniment of the new generation of so-called mental
      patients.

PMID- 16946969
TI  - [Characteristics of the revolving door syndrome at Louis-Hippolyte Lafontaine
      Hospital.].
AB  - This cross-sectional study involving questionnaires examines the influence of
      clinical and socio-demographic variables on read-missions to Louis-H. Lafontaine
      Hospital. Results show a close resemblance between the profile of the 1024
      patients surveyed and that of the complex prototype identified by studies carried
      out in other countries. However, our clientele's characteristics offer a unique
      profile of open-door syndrome. The study's conclusion presents several
      recommendations to help provide more efficient services to the latter clientele.

PMID- 16946970
TI  - [The young adult in psychiatry : the problem and experiences in intervention.].
AB  - Young Adults represent a significant proportion of health care beneficiaries; in
      the field of psychiatry, their proportion is as significant as it is troublesome
      for those dispensing care. Young Adults aged 18 to 35 must rely on short-term
      health care policies that stress deinstitutionalization as the final goal; in
      short, they must deal with solutions that only partially address their problems
      and needs. This article focuses on Young Adults on a treatment center in the
      U.S.A. that specializes in this area and on a project of clinical intervention
      introduced by Louis-H. Lafon-taine Hospital.

PMID- 16946971
TI  - [Short psychiatric hospitalization (less than seven days) : experience at Albert
      Prevost.].
AB  - The authors discuss the available literature on a possible modification of
      traditional hospitalization in psychiatry : the brief hospitalization. Then they
      share a 30 month' experience in a transitory treatment unit at Albert-Prevost.
      Finally, the authors underline the fact that even if research and current use
      promote such an approach, this form of treatment is rare : they look into the
      reasons for such a state of affair.

PMID- 16946972
TI  - [The Coordination of service plans.].
AB  - Several American laws have been passed to co-ordinate various levels of health
      services. The aim is to help patients reintegrate their community, particularly
      for those physically and intellectually handicapped patients, people suffering
      from severe psychological problems and elderly who are increasingly non self
      sufficient. Certain aspects of health care, such as a person's real needs, the
      resources within a person's community, along with consistent and adequate
      services, must be considered if we are to overcome the downside of both budget
      constraints and such a complex health service network. This article reviews the
      author's ten-year experience in the field of mental health in the U.S.A.

PMID- 16946973
TI  - [Two models of services in psychiatric rehabilitation in Great-Britain.].
AB  - Social Psychiatry concepts represent the theoretical basis of British psychiatric
      rehabilitation. Psychiatric disabilities are explained in terms of three
      dimensions: psychiatric impairment, social disadvantages and personal reaction to
      impairment and disadvantages. Psychiatric rehabilitation consists in reducing or
      at least containing disabilities using medical and social treatments to affect
      these 3 dimensions. British Psychiatric services have pionereed
      deinstitutionaliza-tion and community care. However, the development of
      integrated community services has been slow and uneven across the country. Two
      British rehabilitation settings are described. Netherne Hospital, a mental
      hospital with local area respon-sabilities for rehabilitation. Camberwell, where
      admissions to mental hospital has ceased and where District Services Center
      coordinate the rehabilitation activities.

PMID- 16946974
TI  - [The componants of efficiency of community treatment programs for people with
      mental disorders.].
AB  - Community programmes are designed to help clients establish themselves
      permanently in the community to succeed, these programmes must include several
      treatment components each addressing a specific problem presented by the clients.
      These components include : drug therapy, an intervention to encourage clients to
      take medications as prescribed ; an intervention to train staff and clients to
      evaluate symptoms aetiology ; a stable relationship ; social skills training ;
      vocational training or an intervention which aims to help clients participate
      regularly in an activity of their choice ; stress innoculation ; problem solving
      ; an intervention to reduce the use of alcohol ; residences which will provide
      support to the clients.

PMID- 16946975
TI  - [Quality of life : theoretical and empirical perspectives.].
AB  - The idea of maintaining or improving ' 'quality of life' ' is frequently raised
      as a desired objective in mental health intervention. Furthermore, this notion is
      primarily brought up with regard to people who experience severe difficulty in
      living within their community. This article outlines the evolution of such a
      concept, describes certain theoretical models and deals with research data
      concerning factors associated with a positive perception of living conditions.
      Also discussed is the concept's usefulness in the planning and evaluation of
      mental health services.

PMID- 16946976
TI  - [The organization of mental health services in the North-Shore region.].
AB  - During the course of a regional symposium on mental health that took place at
      Sept-iles in October 1986, the author presented his views concerning the
      organization of mental health services in the North Shore region. In this
      article, he develops the two central ideas that supported his presentation.
      Firstly, he attempts to show to what extent it is imperative to deal with the
      issues surrounding alternatives to institutionalization; secondly, he attempts to
      show the importance of operationalizing services offered in small communities, in
      the area of preventive mental health care.

PMID- 16946977
TI  - [In Process Citation]

PMID- 16946978
TI  - ?

PMID- 16946980
TI  - ?

PMID- 16946979
TI  - [In Process Citation]

PMID- 16946982
TI  - ?

PMID- 16946981
TI  - ?

PMID- 16946983
TI  - ?

PMID- 16946984
TI  - [In Process Citation]

PMID- 16946985
TI  - Molecular analysis of a sulphate-reducing consortium used to treat metal
      containing effluents.
AB  - A sulphate-reducing consortium used in a bioprocess to remove toxic metals from
      solution as insoluble sulphides, was characterised using molecular (PCR-based)
      and traditional culturing techniques. After prolonged cultivation under anoxic
      biofilm-forming conditions, the mixed culture contained a low diversity of
      sulphate-reducing bacteria, dominated by one strain closely related to
      Desulfomicrobium norvegicum, identified by three independent PCR-based analyses.
      The genetic targets used were the 16S rRNA gene, the 16S-23S rRNA gene intergenic
      spacer region and the disulfite reductase (dsr) gene, which is conserved amongst
      all known sulphate-reducing bacteria. This organism was also isolated by
      conventional anaerobic techniques, confirming its presence in the mixed culture.
      A surprising diversity of other non-sulphate-reducing facultative and obligate
      anaerobes were detected, supporting a model of the symbiotic/commensal nature of
      carbon and energy fluxes in such a mixed culture while suggesting the
      physiological capacity for a wide range of biotransformations by this stable
      microbial consortium.

PMID- 16946986
TI  - Accumulation of cadmium ions in the methylotrophic yeast Hansenula polymorpha.
AB  - Intracellular cadmium (Cd(2+)) ion accumulation and the ability to produce
      specific Cd(2+) ion chelators was studied in the methylotrophic yeast Hansenula
      polymorpha. Only one type of Cd(2+) intracellular chelators, glutathione (GSH),
      was identified, which suggests that sequestration of this heavy metal in H.
      polymorpha occurs similarly to that found in Saccharomyces cerevisiae, but
      different to Schizosaccharomys pombe and Candida glabrata which both synthesize
      phytochelatins. Cd(2+) ion uptake in the H. polymorpha wild-type strains appeared
      to be an energy dependent process. It was found that Deltagsh2 mutants, impaired
      in the first step of GSH biosynthesis, are characterized by increase in net
      Cd(2+) ion uptake by the cells, whereas Deltagsh1/Deltamet1 and Deltaggt1 mutants
      impaired in sulfate assimilation and GSH catabolism, respectively, lost the
      ability to accumulate Cd(2+) intracellularly. Apparently H. polymorpha, similarly
      to S. cerevisiae, forms a Cd-GSH complex in the cytoplasm, which in turn
      regulates Cd(2+) uptake. Genes GSH1/MET1 and GGT1 are involved in maturation and
      metabolism of cellular Cd-GSH complex, respectively. Transport of [(3)H]N
      ethylmaleimide-S-glutathione ([(3)H]NEM-SG) conjugate into crude membrane
      vesicules, purified from the wild-type cells of H. polymorpha appeared to be
      MgATP dependent, uncoupler insensitive and vanadate sensitive. We suggest that
      MgATP dependent transporter involved in Cd-GSH uptake in H. polymorpha, is
      similar to S. cerevisiae Ycf1-mediated vacuolar transporter responsible for
      accumulation of organic GS-conjugates and Cd-GSH complex.

PMID- 16946987
TI  - Diagnostic contribution of virtual endoscopy in diseases of the upper airways.
AB  - PURPOSE: Virtual endoscopy (VE) is a new diagnostic tool that generates 3
      dimensional (3D) views of a lumen by exploiting cross-sectional images. The
      purpose of this study was to evaluate the usefulness of VE as a diagnostic tool
      in the diseases of the larynx and pharynx. MATERIALS AND METHODS: Twenty-two
      patients with a mean age of 57 years were included in the study. The patients
      underwent larynx examination, optical endoscopy (OE), and computed tomography
      (CT) of the larynx. Later, VE was produced from the CT images. RESULTS: Eight
      patients had larynx carcinoma, a 5-year-old patient had a laryngeal web, a 43
      year-old man had fish bone stuck in his submucosal layer, 10 patients were
      normal, and the remaining two patients were under follow-up for treated
      nasopharynx carcinoma and had no evidence for recurrence. VE showed the laryngeal
      tumor in seven patients and the laryngeal web in one patient, but failed to show
      a plaquelike tumor and the fishbone within the submucosa. CONCLUSIONS: Our
      findings suggest that VE is a useful and complimentary method of 3D imaging in
      the diseases compromising the laryngeal lumen. Furthermore, it may be superior to
      OE in severe stenosis or obstructions where the endoscope cannot be passed
      through.

PMID- 16946988
TI  - Microcatheter tip enhancement in fluoroscopy: a comparison of techniques.
AB  - We compared three techniques for enhancement of microcatheter tips in
      fluoroscopic images: conventional subtraction technique (CST); averaged image
      subtraction technique (AIST), which we have developed; and double average
      filtering (DAF) technique, which uses nonlinear background estimates. A pulsed
      fluoroscopic image sequence was obtained as a microcatheter was passed through a
      carotid phantom that was on top of a head phantom. The carotid phantom was a
      silicone cylinder containing a simulated vessel with the shape and curvatures of
      the internal carotid artery. The three techniques were applied to the images of
      the sequence, then the catheter tip was manually identified in each image, and
      100 x 100 pixel images, centered at the indicated microcatheter tip positions,
      were extracted for the evaluations. The signal-to-noise ratio (SNR) was
      calculated in each of the extracted images from which the mean value of the SNR
      and its standard deviation (SD) were calculated for each technique. The mean
      values and the standard deviations were 4.36 (SD 3.40) for CST, 6.34 (SD 3.62)
      for AIST, and 3.55 (SD 1.27) for DAF. AIST had a higher SNR compared to CST in
      almost all frames. Although DAF yielded the smallest mean SNR value, it yielded
      the best SNR in those frames in which the microcatheter tip did not move between
      frames. We conclude that AIST provides the best SNR for a moving microcatheter
      tip and that DAF is optimal for a temporarily stationary microcatheter tip.

PMID- 16946989
TI  - Budget variance analysis of a departmentwide implementation of a PACS at a major
      academic medical center.
AB  - In this study, the costs and cost savings associated with departmentwide
      implementation of a picture archiving and communication system (PACS) as compared
      to the projected budget at the time of inception were evaluated. An average of
      $214,460 was saved each year with a total savings of $1,072,300 from 1999 to
      2003, which is significantly less than the $2,943,750 projected savings. This
      discrepancy can be attributed to four different factors: (1) overexpenditures,
      (2) insufficient cost savings, (3) unanticipated costs, and (4) project
      management issues. Although the implementation of PACS leads to cost savings,
      actual savings will be much lower than expected unless extraordinary care is
      taken when devising the budget.

PMID- 16946990
TI  - White matter fiber tracking computation based on diffusion tensor imaging for
      clinical applications.
AB  - Fiber tracking allows the in vivo reconstruction of human brain white matter
      fiber trajectories based on magnetic resonance diffusion tensor imaging (MR-DTI),
      but its application in the clinical routine is still in its infancy. In this
      study, we present a new software for fiber tracking, developed on top of a
      general-purpose DICOM (digital imaging and communications in medicine) framework,
      which can be easily integrated into existing picture archiving and communication
      system (PACS) of radiological institutions. Images combining anatomical
      information and the localization of different fiber tract trajectories can be
      encoded and exported in DICOM and Analyze formats, which are valuable resources
      in the clinical applications of this method. Fiber tracking was implemented based
      on existing line propagation algorithms, but it includes a heuristic for fiber
      crossings in the case of disk-shaped diffusion tensors. We successfully performed
      fiber tracking on MR-DTI data sets from 26 patients with different types of brain
      lesions affecting the corticospinal tracts. In all cases, the trajectories of the
      central spinal tract (pyramidal tract) were reconstructed and could be applied at
      the planning phase of the surgery as well as in intraoperative neuronavigation.

PMID- 16946992
TI  - Perineal hernia after proctectomy: prevalence, risks, and management.
AB  - PURPOSE: Perineal hernias are infrequent complications of abdominoperineal
      operations with estimated historic prevalences (from the era where the perineal
      wound was left open) ranging from 0.6 to 7 percent. The purpose of this study was
      to identify the modern prevalence of postoperative perineal hernias, factors that
      may contribute to their development, and examine the methods of repair. METHODS:
      The Mayo Clinic patient database (1990-2000) was interrogated for the following
      data identifiers: incisional hernia, perineal hernia, abdominoperineal resection,
      proctocolectomy, and partial or total pelvic exenteration. All surviving patients
      were followed up to December 2005. The retrieved patient data was retrospectively
      analyzed. RESULTS: Of a total of 3,761 patients who underwent abdominoperineal
      resection (including nonrestorative proctocolectomy and pelvic exenteration)
      during the study period, 8 developed a perineal hernia (5 females). The median
      age at hernia presentation was 76 (range, 69-84) years, representing a median
      interval of 22 (range, 1-60) months from the original operation. All were smokers
      (> or =15 pack years) and five had received chemoradiotherapy for their original
      diagnosis. The commonest prevalence was found in patients who had undergone
      abdominoperineal resection (5/1,266) or pelvic exenteration (2/1,334). Only 1 of
      1,161 patients developed a perineal hernia after proctocolectomy despite most
      being on perioperative immunosuppression for inflammatory bowel disease.
      Abdominal exploration and repair was performed in four patients whereas four
      underwent perineal repair (2 of each with mesh). None have recurred with a median
      follow-up of 36 (range, 6-60) months. CONCLUSIONS: Perineal hernias are rare
      complications of abdominoperineal surgery with a more common prevalence after
      cancer operations. Smoking and chemoradiotherapy, but not corticosteroid
      immunosuppression, may be factors. The abdominal approach has advantages over the
      perineal approach, but both are suitable with good medium-term results.

PMID- 16946993
TI  - Beta2-adrenergic receptor polymorphisms are associated with asthma and COPD in
      adults.
AB  - The beta(2)-adrenergic receptor (beta(2)AR) is a transmembrane protein expressed
      by airway smooth muscle cells. In vitro studies have shown that polymorphisms at
      amino acid positions 16 and 27 alter receptor function. The aim of this study was
      to examine the associations between the beta ( 2 ) AR polymorphisms and risks of
      asthma, chronic obstructive pulmonary disease (COPD) and respiratory symptoms in
      a sample of adults. Participants were part of a cross-sectional population-based
      study of risk factors for respiratory disease. A total of 1,090 Caucasian
      participants completed a detailed respiratory questionnaire, spirometry,
      methacholine challenge and measurement of gas transfer. Genotyping for beta ( 2 )
      AR polymorphisms at positions 16 and 27 was performed using the tetra-primer
      amplification refractory mutation system-polymerase chain reaction (ARMS-PCR)
      method. Haplotype frequencies for the two polymorphisms were estimated using the
      E-M algorithm. We found the Arg16 homozygotes had an increased risk of COPD (OR
      5.13; 95% CI 1.40,18.8), asthma (2.44; 1.12,5.31) and symptoms of wheeze (1.84;
      1.02,3.35). The Gln27 homozygotes had an increased risk of asthma (2.08;
      1.05,4.13) and bronchial hyperreactivity (BHR) (1.92; 1.07,3.46). The Arg16/Gln27
      haplotype was associated with asthma (1.63; 1.12,2.38) and COPD (2.91;
      1.42,5.94). The Arg16/Gln27 beta(2)AR haplotype is important in COPD, asthma and
      BHR, and may be associated with more severe respiratory symptoms in middle-aged
      and older adults.

PMID- 16946994
TI  - A founder mutation for ichthyosis prematurity syndrome restricted to 76 kb by
      haplotype association.
AB  - Autosomal recessive congenital ichthyosis (ARCI) is a group of keratinisation
      disorders that includes the ichthyosis prematurity syndrome (IPS). IPS is rare
      and almost exclusively present in a restricted region in the middle of Norway and
      Sweden, which indicates a founder effect for the disorder. We recently reported
      linkage of IPS to chromosome 9q34, and we present here the subsequent fine
      mapping of this region with known and novel microsatellite markers as well as
      single nucleotide polymorphisms (SNPs). Allelic association, evaluated with
      Fisher's exact test and P (excess), was used to refine the IPS haplotype to
      approximately 1.6 Mb. On the basis of the average length of the haplotype in IPS
      patients, we calculated the age of a founder mutation to approximately 1,900
      years. The IPS haplotype contains a core region of 76 kb consisting of four
      marker alleles shared by 97.7% of the chromosomes associated with IPS. This
      region spans four known genes, all of which are expressed in mature epidermal
      cells. We present the results from the analysis of these four genes and their
      corresponding transcripts in normal and patient-derived samples.

PMID- 16946995
TI  - Novel mutation in the HSN2 gene in a Korean patient with hereditary sensory and
      autonomic neuropathy type 2.
AB  - Hereditary sensory and autonomic neuropathies (HSAN) are a group of clinically
      and genetically heterogeneous disorders that are associated with sensory
      dysfunction. Among these, HSAN type 2 (HSAN2; MIM 201300) is a rare recessive
      disease that is characterized by an early age of onset with distal and proximal
      sensory loss, dysfunction of the autonomic nervous system, loss of the tendon
      reflex, the presence of various mutilations, and the slow progression of the
      disease over time. The authors report a Korean patient with the clinical features
      of HSAN2, who was compound heterozygous for two loss-of-function mutations in the
      HSN2 gene: c.217C > T (Gln73X) and c.1134_1135insT (Asp379fsX1). The Gln73X
      mutation was a novel mutation while the Asp379fsX1 mutation has recently been
      reported in a Japanese patient with HSAN2. These results expanded the spectrum of
      mutations of the HSN2 gene by identifying a novel truncating mutation in a Korean
      patient and further support the hypothesis that HSN2 is a causative gene for
      HSAN2.

PMID- 16946996
TI  - Role of B cell inhibitory receptor polymorphisms in systemic lupus erythematosus:
      a negative times a negative makes a positive.
AB  - B lymphocytes play a pivotal role in the pathogenesis of systemic lupus
      erythematosus (SLE). Here, we will review our studies on the role of
      polymorphisms of two genes coding for B cell inhibitory receptors, FCGR2B and
      CD72. In FCGR2B, a single nucleotide polymorphism leading to a nonsynonymous
      substitution, Ile232Thr, within the transmembrane domain was identified, and a
      significant association of the 232Thr/Thr genotype with SLE was observed in
      Japanese, Thai and Chinese populations, while this allele was found to be rare in
      Caucasians. On the other hand, the association of FCGR2B promoter polymorphism
      with SLE in Caucasians has been reported by two independent groups, but this
      allele was not found to be present in Japanese. These observations demonstrate
      that the association of FCGR2B polymorphisms with SLE is common to multiple
      populations, but the alleles associated with SLE depend upon the genetic
      background of each population. Functional analyses using a human B cell line
      lacking endogenous FcgammaRIIb revealed that SLE-associated 232Thr allele product
      was partially excluded from membrane lipid rafts under resting conditions and
      after coligation with B cell receptor, and was significantly less potent at
      inhibiting B cell activation. Two haplotypes were identified in CD72, one of
      which was associated with increased production of an alternative splicing isoform
      that substantially alters the extracellular region of CD72. Interestingly, the
      presence of the haplotype significantly decreased the risk of SLE conferred by
      FCGR2B-232Thr in an epistatic manner. These observations emphasize the need to
      understand human immune system diversity if we are to improve our understanding
      of the pathogenesis of autoimmune diseases.

PMID- 16946997
TI  - Occurrence of sacroiliitis in patients with seronegative oligoarthritis.
AB  - The aim of this study was to investigate sacroiliitis in patients with
      seronegative oligoarthritis. Thirty consecutive patients with seronegative
      oligoarthritis and no other signs of spondylarthropathy were included. Sacroiliac
      (SI) joints were investigated by both radiography and magnetic resonance imaging.
      HLA B27 antigen was studied and family history was reexamined in 2006. Five
      patients had sacroiliitis. Additionally, 15 patients had HLA B27 antigen or
      family history of either psoriasis or ankylosing spondylitis. Our conclusion is
      that during the first decade of seronegative oligoarthritis, HLA B27 antigen,
      family history, and especially imaging of SI joints reveal in two thirds of the
      patients the spondylarthritic nature of their disease.

PMID- 16946998
TI  - A semi-physiological population pharmacokinetic model describing the non-linear
      disposition of indisulam.
AB  - The pharmacokinetic profile of the anti-cancer agent indisulam is non-linear. In
      addition to non-linear clearance, this may partially be explained by saturable
      distribution to red blood cells and saturable plasma protein binding. The aims of
      this study were to develop a semi-physiological population pharmacokinetic model
      of indisulam and to examine the impact of protein binding and distribution to red
      blood cells. Indisulam concentrations in plasma, plasma ultrafiltrate and in red
      blood cells from multiple phase I studies in Caucasian and Japanese patients were
      used to develop a pharmacokinetic model using NONMEM. This model comprised four
      physiological compartments: plasma, red blood cells, interstitial fluid and
      tissue. A simulation study was performed to examine the contribution of
      physiological processes in indisulam pharmacokinetics. Plasma albumin
      concentrations were predictive for the maximal protein binding capacity and
      considerably influenced total plasma concentrations of indisulam, whereas free
      plasma concentrations remained relatively unaffected. The maximal specific red
      blood cell binding capacity was 64.0 ( +/-5.9) mg/L and corresponded to the
      typical red blood cell carbonic anhydrase concentration. Simulation studies
      demonstrated that the hematocrit does not have a clinically relevant impact on
      indisulam disposition. This semi-physiological model allowed adequate prediction
      of the time profiles of indisulam concentrations in all monitored compartments
      for a large range of dose levels and several treatment regimens. The model has
      elucidated the mechanism and the role of saturable plasma protein binding and
      saturable distribution to red blood cells in indisulam pharmacokinetics and
      provides a basis for rationale PK-PD relationships.

PMID- 16947000
TI  - Natural conception after age 45 in Bedouin women, a uniquely fertile population.
AB  - PURPOSE: Women conceiving naturally and delivering after age 45 are an
      exceptionally fertile population that may serve as a model to identify factors
      associated with delayed reproductive aging. This work studies this phenomenon in
      Bedouin women. METHODS: The study is an observational retrospective analysis of
      all Bedouin women who conceived spontaneously and had their latest delivery after
      the age of 45 years, during the years 1995-2000 at the participating medical
      center. Complete histories of the outcomes of all pregnancies were collected.
      RESULTS: 133 of 34,519 (0.38%) Bedouin women gave birth after the age of 45
      years. The mean maternal age at last delivery was 46+/-1.4 years (range: 45-52),
      and the mean parity was 11.6+/-2.9 children (range: 3-18). 96% were
      grandmultiparous (> or =6 deliveries). The mean spontaneous abortion rate (6.6%)
      was not affected by increased parity and was significantly lower than in the
      general population: 12.4% vs.17.7% at age 39, 5% vs. 33.8% (p < 0.001) at age 44
      and 1.8% vs. 53.2% (p < 0.001) at age 45. CONCLUSIONS: This unique group of
      Bedouin women may have a genetic predisposition to delayed ovarian and oocyte
      aging.

PMID- 16946999
TI  - Intracytoplasmic sperm injection (ICSI) in unexplained and stage I endometriosis
      associated infertility after fertilization failure with in vitro fertilization
      (IVF).
AB  - PURPOSE: To investigate possible differences between unexplained and stage I
      endometriosis-associated infertility in ICSI cycles conducted after low
      fertilization (<20%) in preceding IVF cycles with normal semen parameters.
      METHODS: Retrospective cohort study consisting of patients with unexplained
      (n=48) and stage I endometriosis-associated infertility (n=43) with a minimum of
      one IVF cycle with <20% fertilized oocytes and normal semen quality, treated with
      ICSI from January 1997 to January 2006. Age matched male factor infertility
      patients (n=91) were used as controls. RESULTS: Diploid fertilization rate was
      significantly lower in the stage I endometriosis-associated infertility group
      compared to the unexplained infertility group. Score of the transferred embryos,
      implantation rate, pregnancy rate and outcome were similar in the two groups.
      CONCLUSIONS: ICSI appears to be an efficient treatment option after fertilization
      failure with IVF in unexplained and stage I endometriosis-associated infertility.

PMID- 16947001
TI  - Caregiver, child, family, and service system contributors to caregiver strain in
      two child mental health service systems.
AB  - Children's mental health researchers are increasingly recognizing the importance
      of caregiver strain (i.e., the impact on families of caring for children with
      emotional and behavioral disorders). This study examined the caregiver, child,
      family, and service variables associated with caregiver strain with special
      attention to the role of barriers to care. These relationships were compared
      across enrollees in a managed care Medicaid and a traditional fee-for-service
      system. Findings indicated that severity of child problems was the most
      consistent predictor of caregiver strain. Although there was considerable
      similarity in the variables associated with caregiver strain across the two
      systems, important differences were also evident. Caregivers in the managed care
      setting were significantly more likely to report provider/payer-related barriers
      to care. Provider/payer barriers predicted strain in the managed care sample. In
      the fee-for-service system, barriers related to family perceptions and
      inconvenient location and appointment times were significant predictors.

PMID- 16947002
TI  - HMG-CoA reductase inhibitors inhibit rat propylthiouracil-induced goiter by
      modulating the ras-MAPK pathway.
AB  - The aim of this study was to evaluate in vivo the antiproliferative effect of an
      inhibitor of isoprenoids metabolism, lovastatin, in an experimental model of
      propylthiouracil-induced goiter. In thyroid cells, thyrotropin (TSH)-induced
      proliferation requires active isoprenoid synthesis, and the HMG-CoA reductase
      inhibitors have antiproliferative effects in vitro. Propylthiouracil treatment
      (PTU) of rats led to thyroid hypertrophy and hyperplasia by TSH-induced
      activation of the mitogen-activated protein kinase (MAPK) pathway.
      Immunohistochemistry showed an increased number of proliferating cell nuclear
      antigen (PCNA)-positive cells in the thyroid gland of PTU-treated rats. Moreover,
      the phosphorylation of ERK1 and ERK2 was increased in the extract from goiter
      tissue as compared with the thyroid tissue of untreated rats. To determine
      whether the inhibition of selected pro-survival pathways (i.e., p21ras-MAPK) was
      sufficient to affect goitrogenesis, thyroids from 12 PTU-treated rats were
      injected in vivo with an adenovirus transducing a dominant-negative ras gene (Rad
      L61.S186) and another set of 12 rats were injected with a pharmacological
      inhibitor of MAPK (PD98059). Both Rad-L61.S186 and PD98059 were able to inhibit
      the PTU-induced goiter. It is interesting to note that lovastatin, when
      administered in drinking water, significantly prevented the thyroid gland
      enlargement. Therefore, lovastatin-treated thyroid glands were significantly
      smaller than those treated with PTU alone. In addition, the lovastatin-treated
      glands also showed a decreased expression of phosphorylated ERK1/2 and a number
      of PCNA-positive cells. Our data suggest that lovastatin is an efficient
      inhibitor of goitrogenesis and provide a rationale for innovative therapeutic
      strategies employing statins in the treatment of nodular goiter in humans.

PMID- 16947004
TI  - Increased CYP1A1 expression in human exfoliated urothelial cells of cigarette
      smokers compared to non-smokers.
AB  - Polycyclic aromatic hydrocarbons, arylamines and nitrosamines, constituents of
      cigarette smoke, are known inducers of bladder cancer. The biochemical response
      of the target tissue, the bladder urothelium, following inhalation of cigarette
      smoke has not been studied so far. We used exfoliated transitional urothelial
      cells from human urine samples to analyze effects of smoking on induction of the
      cytochrome P450 enzyme CYP1A1. Samples of 40 subjects, including male and female
      smokers and non-smokers, were examined. A prerequisite for the immunofluorescence
      microscopic analysis of the cells was the enrichment of the urothelial cell
      population. This was achieved by a new method which is based on magnetic cell
      sorting exploiting specific binding of immobilized Griffonia simplicifolia lectin
      to the surface of urothelial cells. Immunostaining of the final cell preparation
      with a monoclonal antibody to CYP1A1 showed that about 6% of the urothelial cells
      of non-smokers stained positive for CYP1A1. However, this fraction of positive
      cells was more than 44% of the urothelial cells in samples from cigarette
      smokers. In spite of the individual variation, the difference was statistically
      significant. There were no gender-related differences in the portion of CYP1A1
      expressing urothelial cells of smokers and non-smokers. In essence, we show for
      the first time that human urothelial cells respond to cigarette smoking by
      induction of CYP1A1. The approach opens new fields of mechanistic and biomarker
      research with respect to the pathogenetic processes of cancer development in the
      human bladder.

PMID- 16947003
TI  - TBG deficiency: description of two novel mutations associated with complete TBG
      deficiency and review of the literature.
AB  - Thyroxine-binding globulin (TBG) is the main thyroid hormone transport protein in
      serum. Inherited TBG defects lead to a complete (TBG-CD) or a partial (TBG-PD)
      deficiency and have a diagenic transmission, being clinically fully expressed
      only in hemizygous males and in homozygous females. In the present study, seven
      patients from two unrelated families with TBG-CD were studied and two novel TBG
      mutations were documented. In particular, a T insertion at the 5' donor splice
      site of exon 0, between nucleotides 2 and 3 at the beginning of intron 1
      (g.IVS1+2_3insT) was found in one family and was named TBG-Milano. The other
      novel mutation is a T deletion at nucleotide 214 of exon 1, which leads to a
      frameshift at codon 50 with a premature stop codon at position 51 (c.214delT,
      P50fsX51) and was named TBG-Nikita. According to the X-linked transmission of the
      defect, females harboring the mutation showed a reduction in TBG levels with
      normal TSH and total thyroid hormone values at the lower limit of normal. Males
      harboring either TBG-Milano or TBG-Nikita, showed normal TSH values and low
      levels of total thyroid hormones and lacked TBG. In conclusion, we report two
      novel mutations of the TBG gene associated with a complete TBG defect. The first
      mutation lies at the 5' donor splice site of exon 0 and probably alters the start
      of translation, while the second is a single nucleotide deletion and leads to a
      premature stop codon.

PMID- 16947005
TI  - Applications of microwave-assisted processes (MAP) to environmental analysis.
AB  - The use of microwave-assisted extraction has gained wide acceptance as a powerful
      tool for the recovery of environmental contaminants and their subsequent
      analysis. This paper reviews the historical and fundamental basis of the
      technology. It also provides a cursory review of the current state-of-the-art and
      literature (2000-2006) in the area of environmental analysis in addition to
      providing a critical review of the level of efforts being devoted to its further
      development.

PMID- 16947006
TI  - Fluorescence sensor using a molecularly imprinted polymer as a recognition
      receptor for the detection of aluminium ions in aqueous media.
AB  - This paper describes the investigation of a molecularly imprinted polymer (MIP)
      as a sensing receptor for Al(3+) ion detection by using an optical approach.
      Al(3+) ion was adopted as the template molecule and 8-hydroxyquinoline sulfonic
      acid ligand as the fluorescence tag. The polymer was synthesised using acrylamide
      as monomer, 2-hydroxyethyl methacrylate as co-monomer and ethylene glycol
      dimethracylate as cross-linker. The free radical polymerisation was performed in
      methanol and initiated by 2,2'-azobisisobutyronitrile at 70 degrees C. The
      imprinted polymer was fluorometrically characterised using a fibre optic
      attachment in a self-designed flow-cell. NaF was used to leach the Al(3+) ion
      from the MIP. The optimum pH for the rebinding of Al(3+) ion with the leached
      polymer was found to be pH 5 and the fluorescence response was found to be stable
      within the buffer strength range of 0.05-0.10 M. The fluorescence intensity
      during Al(3+) ion rebinding was inversely dependent on temperature, and a low
      interference response (<3%) toward metal ions except for Cu(2+) and Zn(2+) ions
      was observed. The polymer rebinding repeatability study conducted over 9 cycles
      with Al(3+) ion (0.8 x 10(-4) M) was found to give an RSD value of 2.82% with a
      standard deviation of 0.53. The dynamic range of the system was found to be
      linear up to 1.0 x 10(-4) M Al(3+) ion with a limit of detection of 3.62 microM.

PMID- 16947007
TI  - A novel competitive fluorescence immunoassay for the determination of dibutyl
      phthalate.
AB  - A novel, sensitive, and specific competitive fluorescence immunoassay has been
      developed for the quantitative determination of dibutyl phthalate (DBP) using an
      antibody-coated plate format. Hapten was synthesized in order to produce
      polyclonal antibodies against dibutyl phthalate. Polyclonal antisera to dibutyl
      phthalate were generated in rabbits and used to construct the fluorescence
      immunoassay for measurement of dibutylphthalate. The assay had a detection limit
      of about 0.02 microg L(-1), a dynamic range of approximately 0.1-300 microg L(
      1). Other similar phthalate compounds do not interfere significantly in the
      analysis using this immunoassay technique, and the cross-reactivity rates were
      less than 10%. The study demonstrated that the developed antiserum and
      fluorescence immunoassay procedure can be used to detect dibutyl phthalate in
      environmental samples such as tap water, river water, drinking water, and
      leachate from plastic drinking water bottles.

PMID- 16947008
TI  - Learning curve for total gastrectomy with D2 lymph node dissection: cumulative
      sum analysis for qualified surgery.
AB  - BACKGROUND: This study was conducted to evaluate the leaning curve of D2 lymph
      node dissection for patients with gastric cancer in a high-volume center.
      METHODS: The authors prospectively reviewed the data of all patients who
      underwent total gastrectomy with D2 lymph node dissection during a 4-year period.
      Retrieved lymph node number was used as a surrogate marker of oncological
      outcome. The retrieved lymph node number cut-off value required for satisfactory
      D2 lymph node dissection was defined as >25. Cumulative sum analysis was used to
      examine the learning curves of individual surgeons at target accuracy rates of
      85%, 90%, 92.5%, 95%, and 98%. RESULTS: Two junior staff surgeons performed 198
      curative-intent total gastrectomies with D2 lymph node dissections during the
      study period; their success rates exceeded 90%. Operating time decreased with
      operative experience (Pearson correlation coefficient = -0.515, P < 0.001). The
      learning period for total gastrectomy with D2 lymph node dissection for these two
      junior members of staff was calculated as 23-35 cases, presuming a 92.5% success
      rate. CONCLUSIONS: The current study suggests that the surgical learning period
      for D2 lymph node dissection extends to at least 23 cases or 8 months. In
      clinical trials containing gastric cancer surgery, the learning curve for
      qualified surgery from the standpoint of oncological outcome should be considered
      to minimize bias due to surgeon-associated factors.

PMID- 16947009
TI  - Selection of patients for resection of hepatic colorectal metastases: expert
      consensus statement.

PMID- 16947011
TI  - Alternate lung collapse in a 9-year-old boy with peanut aspiration.

PMID- 16947010
TI  - Analysis of the utility of diffusion-weighted MRI and apparent diffusion
      coefficient values in distinguishing central nervous system toxoplasmosis from
      lymphoma.
AB  - INTRODUCTION: Toxoplasmosis and lymphoma are common lesions of the central
      nervous system in patients with AIDS. It is often difficult to distinguish
      between these lesions both clinically and radiographically. Previous research has
      demonstrated restricted diffusion within cerebral lymphomas and bacterial
      abscesses. However, little work has been done to evaluate the diffusion
      characteristics of toxoplasmosis lesions. This study was designed to explore
      further the utility of diffusion-weighted imaging (DWI) and apparent diffusion
      coefficient (ADC) maps and values in making the distinction between toxoplasmosis
      and lymphoma. METHODS: The magnetic resonance imaging (MRI) studies of 36
      patients, including 22 with toxoplasmosis (all of whom had AIDS) and 14 with
      lymphoma (8 of whom had AIDS), at two institutions were reviewed retrospectively.
      The characteristics of the lesions on DWI were evaluated, and the ADC ratios of
      the lesions were calculated and compared. RESULTS: There was significant overlap
      of the ADC ratios of toxoplasma and lymphoma, most notably in the intermediate
      (1.0-1.6) range. There was variability in ADC ratios even among different lesions
      in the same patient. In only a minority of the lymphoma patients were the ADC
      ratios low enough to suggest the correct diagnosis. CONCLUSION: Our study showed
      that toxoplasmosis exhibits a wide spectrum of diffusion characteristics with ADC
      ratios which have significant overlap with those of lymphoma. Therefore, in the
      majority of patients, ADC ratios are not definitive in making the distinction
      between toxoplasmosis and lymphoma.

PMID- 16947012
TI  - Histological changes in bladders of patients submitted to ifosfamide chemotherapy
      even with mesna prophylaxis.
AB  - PURPOSE: Hemorrhagic cystitis (HC) is a limiting side effect of chemotherapy with
      ifosfamide (IFS). Mesna is the drug of choice for prevention of HC. In this
      study, we analyzed cystoscopic and histological changes present in bladders of
      patients using IFS with mesna prophylaxis. METHODS: Thirty-three patients
      selected for IFS plus three doses of mesna chemotherapy regime were assigned at
      random to two groups: Group I or reference group consisted of 18 patients yet
      untreated. Group II consisted of 15 patients in whom urinalysis and cystoscopy
      plus vesical biopsy were performed only 24 h after receiving the last dose of
      IFS. The cystoscopic and histological findings were used as parameters for
      evaluating the results. For the former the criterion adopted was macroscopic
      vesical changes in accordance with Gray's criteria. Histological analyses were
      performed by evaluation method especially adapted to this study. RESULTS: Even
      under treatment with three doses of mesna, 66.7% of patients presented
      cystoscopic alterations and 100% showed bladder mucosa microscopic alterations
      such as edema, exocytosis, and hemorrhage. CONCLUSIONS: The standard protocol
      used for prevention of IFS-induced HC with three doses of mesna does not
      completely prevent bladder damage. The histopathological criteria used in this
      study for observation of inflammatory events allowed staging the intensity of IFS
      induced urothelial and mucosal injury.

PMID- 16947013
TI  - Assessment of the abdominal aorta and its visceral branches by contrast-enhanced
      dynamic volumetric hepatic parallel magnetic resonance imaging: feasibility,
      reliability and accuracy.
AB  - The purpose of this study was to evaluate a new three-dimensional gradient-echo
      (GRE) MR sequence performed with a parallel acquisition technique to shorten
      breath-hold times (parallel GRE MRI) in the detection of arterial variants and
      stenosis of the abdominal aorta and its visceral branches. A total of 102
      patients underwent dynamic parallel GRE MRI, timed to the arterial phase by a
      test bolus (mean breath-hold time, 17 s). For both quantitative and qualitative
      analysis, the abdominal aorta and its visceral branches were divided into 13
      arterial segments. In a subanalysis of 55/102 patients, the accuracy of parallel
      GRE MRI compared to MDCT in the detection arterial variants and stenosis was
      calculated for two independent readers. Mean SNRs and CNRs were 47.2 and 35.6,
      respectively. Image quality was rated good or excellent in 1,234/1,326 segments
      (93%). Hepatic and renal arterial variants were identified with an accuracy of 93
      and 95%, respectively (reader 1) and 98 and 100%, respectively (reader 2). Both
      readers detected arterial stenosis with an accuracy of 98%. Interobserver
      agreement was good to excellent for the detection of hepatic (kappa=0.69) and
      renal (kappa=0.92) variants and for the diagnosis of stenosis (kappa=0.96).
      Dynamic three-dimensional parallel GRE MRI is feasible and allows a reliable and
      accurate diagnosis of arterial variants and stenosis of the abdominal aorta and
      its visceral branches in a short breath-hold-time.

PMID- 16947014
TI  - Two novel serum-free media for the culture of Trichomonas vaginalis.
AB  - Definitive diagnosis of Trichomonas vaginalis, one of the common causes of
      sexually transmitted diseases in Turkey, relies on the microscopic examination of
      both fresh preparations and culture material of genital secretions and urine. The
      aim of this study was to compare the diagnostic efficacies of two culture media,
      serum-free TB1 and TB2, including iron and vitamin B12, respectively, with the
      well-known medium, TYM. Growth rate reached peak levels 48 h in TYM and 72 h in
      both TB1 and TB2 after inoculation. The highest amount of viable trophozoites has
      been obtained from TB1, almost equal to TYM but significantly higher than TB2.
      Fresh preparations obtained from the vaginal secretions of 119 patients have been
      examined and vaginal samples have been inoculated in TB1, TB2, and TYM. Viable T.
      vaginalis trophozoites have been detected in ten (8.4%) of fresh preparations and
      11 (9.9%) of each medium. It is concluded that serum-free TB1 medium could be
      used effectively in both the isolation and maintenance of T. vaginalis culture in
      vitro.

PMID- 16947015
TI  - Temporo-spatial distribution of blood vessels in human lumbar intervertebral
      discs.
AB  - While there is consensus in the literature that blood vessels are confined to the
      outer anulus fibrosus of normal adult intervertebral disc, debate continues
      whether there is a vascular in-growths into inner parts of the intervertebral
      disc during degeneration. We therefore tested the hypothesis that vascular in
      growth is not a distinct feature of disc degeneration. The specific endothelial
      cell marker CD 31 (PECAM) was used to immunohistochemically investigate 42
      paraffin-embedded complete mid-sagittal human intervertebral disc sections of
      various ages (0-86 years) and varying extent of histomorphological degeneration.
      Additionally, 20 surgical disc samples from individuals (26-69 years) were
      included in this study. In discs of fetal to infantile age, blood vessels
      perforated the cartilaginous end plate and extended into the inner and outer
      anulus fibrosus, but not into the nucleus pulposus. In adolescents and adults, no
      blood vessels were seen except for the outer zone of the anulus fibrosus adjacent
      to the insertion to ligaments. The cartilaginous end plate remained free of
      vessels, except for areas with circumscribed destruction of the end plate. In
      advanced disc degeneration, no vessels were observed except for those few cases
      with complete, scar-like disc destruction. However, some rim lesions and
      occasionally major clefts were surrounded by a small network of capillary blood
      vessels extending into deeper zones of the anulus fibrosus. A subsequent
      morphometric analysis, revealed slightly "deeper" blood vessel extension in
      juvenile/adolescent discs when compared to young, mature and senile adult
      individuals with significantly "deeper" extension in the posterior than anterior
      anulus. The analysis of the surgical specimens showed that only sparse capillary
      blood vessels which did not extend into the nucleus pulposus even in major disc
      disruption. Our results show that vascular invasion deeper than the periphery was
      not observed during disc degeneration, which supports the hypothesis that
      vascular in-growth is not a distinct feature of disc degeneration.

PMID- 16947016
TI  - Dorsal dumb-bell melanotic schwannoma operated on by posterior and anterior
      approach: case report and a review of the literature.
AB  - The schwannomas are benign tumors originating from Schwann cells which constitute
      the nerve sheath. The dorsal pigmented type of schwannomas is relatively rare
      (Goldstein in Am J Med Genet 86:62-65, 2004; Kurtkaya-Yapicier in Histol
      Histopathol 18(3):925-934, 2003). There are two distinct types of melanotic
      schwannoma: the sporadic melanotic schwannomas and the psammomatous melanotic
      schwannomas of Carney complex. We report a case of a patient harboring a right
      dorsal dumb-bell melanotic schwannoma and left adrenal mass. The patient
      underwent a surgical procedure for en bloc total removal of the mass by a
      posterior and anterior approach. Histopathological examination revealed the
      diagnosis of melanotic schwannoma. At present, we have no reliable marker of
      histopathological malignancy of melanotic schwannoma so the follow-up period
      ought to continue for a period of more than 5 years. As the total removal of the
      melanotic neurinomas is mandatory to prevent possible malignant transformation of
      the tumor recurrence or regrowth, we believe that the posterior and trans
      thoracic approach are the most suitable one for the dorsal dumb-bell schwannoma.

PMID- 16947018
TI  - The cannabinoid receptor agonist WIN 55,212-2 facilitates the extinction of
      contextual fear memory and spatial memory in rats.
AB  - RATIONALE: Previous studies demonstrated that pharmacological blockade of CB1
      cannabinoid receptors decreases the extinction of conditioned fear and spatial
      memory in rodents. However, the effects of CB1 cannabinoid receptor activation in
      this response remain unclear. OBJECTIVES: To evaluate the effects of the
      cannabinoid agonist WIN 55,212-2 (WIN) and the cannabinoid antagonist SR 147778
      (SR) on the extinction of contextual fear memory in rats 24 h or 30 days after
      fear conditioning. METHODS: For fear conditioning, rats were placed in the
      conditioning chamber for 3 min and received a 1-s electric foot shock (1.5 mA).
      Retrieval testing consisted of a 3-min exposure to the conditioning chamber and
      extinction training consisted of successive 9-min exposures at 24-h intervals.
      Rats were also evaluated in the open field and water maze reversal task. RESULTS:
      The administration of SR (1.0 mg/kg, i.p.) and WIN (0.25 mg/kg, i.p.) before
      extinction training disrupted and facilitated, respectively, the extinction of 24
      h contextual fear memory. These effects were not related to any disturbance in
      memory retrieval, unconditioned freezing expression, or locomotor activity. WIN
      (0.25 mg/kg, i.p.) also facilitated the extinction of 30-day-old contextual fear
      memory, while the prior administration of SR (0.2 mg/kg, i.p.) antagonized this
      response. The facilitative effect of WIN on memory extinction does not seem to be
      specific for contextual fear memory because it was also observed in the water
      maze reversal task. CONCLUSIONS: These results suggest cannabinoid receptor
      agonists as potential drugs to treat anxiety disorders related to the retrieval
      of aversive memories.

PMID- 16947017
TI  - Lamotrigine inhibits basal and Na+-stimulated, but not Ca2+-stimulated, release
      of corticotropin-releasing hormone from the rat hypothalamus.
AB  - RATIONALE: Corticotropin-releasing hormone (CRH) is a peptide neurotransmitter
      involved in the pathogenesis of anxiety and depressive disorders; CRH receptor
      antagonists are currently developed as anxiolytic and antidepressive agents, and
      several antidepressants negatively modulate CRH in the central nervous system.
      OBJECTIVES AND METHODS: Originally marketed as an antiepileptic drug, lamotrigine
      (LTG) was subsequently shown to be effective as a mood stabilizer and an
      antidepressant. In this study, we used acute rat hypothalamic explants to
      investigate the effects of LTG on the gene expression and secretion of CRH from
      the hypothalamus in short-term incubation experiments. RESULTS: We found that LTG
      reduces basal CRH release in a time- and concentration-dependent manner. LTG also
      inhibits veratridine-stimulated, but not K+-stimulated, CRH release in 1-h
      experiments. Moreover, LTG tended to reduce CRH mRNA expression in 1-h
      experiments, regardless of whether the drug was given alone or in combination
      with veratridine or high K+ concentrations; such reduction achieved statistical
      significance after 3 h of incubation. CONCLUSION: In 1-h experiments, LTG reduces
      CRH release from CRH-containing neurons in the rat hypothalamus by interfering
      with Na+-driven secretion mechanisms. After 3-h incubations, the reduction in CRH
      release is also accounted for by LTG-induced decrease in CRH gene expression.

PMID- 16947019
TI  - T cell responses in melanoma patients after vaccination with tumor-mRNA
      transfected dendritic cells.
AB  - We have developed an individualized melanoma vaccine based on autologous
      dendritic cells (DCs) transfected with autologous tumor-mRNA. The vaccine targets
      the unique spectrum of tumor antigens in each patient and may recruit multiple T
      cell clones. In a recent phase I/II trial, we demonstrated T cell responses
      against vaccine antigens in 9/19 patients evaluable by T cell assays. Here, we
      report a follow-up study that was conducted to characterize interesting T cell
      responses and to investigate the effects of long-term booster vaccination. Two
      patients were selected for continued vaccine therapy. The clinical follow-up
      suggested a favorable clinical development in both patients. The immunological
      data (T cell proliferation/IFNgamma ELISPOT/Bioplex cytokine assays) indicated
      sustained T cell responses and suggested an enhancing effect of booster
      vaccinations. Both CD4(+) and CD8(+) T cell responses were demonstrated. From
      post-vaccination samples, we generated 39 T cell clones that responded
      specifically to stimulation by mRNA-transfected DCs and 12 clones that responded
      to mock-transfected DCs. These data clearly indicate a two-component vaccine
      response, against transfected and non-transfected antigens. T cell receptor (TCR)
      clonotype mapping, performed on 11 tDC-specific clones, demonstrated that 10/11
      clones had different TCRs. The results thus indicate a broad spectrum T cell
      response against antigens encoded by the transfected tumor-mRNA. We generally
      observed mixed Th1/Th2 cytokine profiles, even in T cell clones that were
      confirmed to be derived from a single cell. This finding suggests that cytokine
      patterns after cancer vaccination may be more complex than indicated by the
      classic Th1/Th2 dichotomy.

PMID- 16947020
TI  - Activation of complement C3, C5, and C9 genes in tumors treated by photodynamic
      therapy.
AB  - Cancer therapies, which deliver a rapidly induced massive tumor tissue injury,
      such as photodynamic therapy (PDT), provoke a strong host response raised for
      dealing with the inflicted local trauma. Activated complement system was
      identified as an important element of host response elicited by tumor PDT. The
      expression of genes encoding complement proteins C3, C5, and C9 was studied
      following tumor PDT mediated by photosensitizer Photofrin using mouse Lewis lung
      carcinoma (LLC) model. Treated tumors and the livers of host mice were collected
      at different times after PDT and the expression of the investigated genes was
      analyzed by RT-PCR. The results show a significant up-regulation of C3, C5, and
      C9 genes in PDT-treated tumors at 24 h after therapy, while no significant
      increase in the expression of these genes was found in the liver tissues. The
      expression of C3, C5, and C9 genes also became up-regulated in untreated tumor
      associated macrophages (TAMs) co-incubated in vitro with PDT-treated LLC cells.
      This effect was abolished or drastically reduced in the presence of antibodies
      blocking heat shock protein 70 (HSP70), Toll-like receptor (TLR) 2 and TLR4, and
      specific peptide inhibitors of TIRAP adapter protein and transcription factor NF
      kappaB. The presented study reveals that complement genes C3, C5, and C9 become
      up-regulated in tumors treated by PDT, but not in the host's liver. Tumor
      localized up-regulation of these genes can be largely attributed to
      monocytes/macrophages invading the treated lesion after PDT. This effect appears
      to be induced by the recognition of danger signals from PDT-treated tumor cells
      such as HSP70 by TAMs that involve the TLR2- and TLR4-triggered signal
      transduction pathways leading to the activation of NF-kappaB.

PMID- 16947021
TI  - Bee venom secretory phospholipase A2 and phosphatidylinositol-homologues
      cooperatively disrupt membrane integrity, abrogate signal transduction and
      inhibit proliferation of renal cancer cells.
AB  - Bee venom secretory phospholipase A2 (bv-sPLA2) and phosphatidylinositol-(3,4)
      bisphosphate (PtdIns(3,4)P2) act synergistically to induce cell death in tumour
      cells of various origins with concomitant stimulation of the immune system. Here,
      we investigated the mechanisms involved in such actions and examined structural
      requirements of PtdIns-homologues to inhibit tumour cells in combination with bv
      sPLA2. Renal cancer cells were treated with bv-sPLA2 alone or in combination with
      PtdIns-homologues. Inhibitory effects on [(3)H] thymidine incorporation and
      intracellular signal transduction pathways were tested. Reaction products
      generated by bv-sPLA2 interaction with PtdIns(3,4)P2 were identified by mass
      spectrometry. Among the tested PtdIns-homologues those with a phosphate
      esterified to position 3 of the inositol head group, were most efficient in
      cooperating with bv-sPLA2 to block tumour cell proliferation. Growth inhibition
      induced by the combined action of bv-sPLA2 with either PtdIns(3,4)bisphosphate or
      PtdIns(3,4,5)trisphosphate were synergistic and accompanied by potent cell lysis.
      In contrast, PtdIns, which lacked the phosphate group at position 3, failed to
      promote synergistic growth inhibition. The combined administration of
      PtdIns(3,4)P2 and bv-sPLA2 abrogated signal transduction mediated by
      extracellular signal regulated kinase 1 and 2 and prevented transduction of
      survival signals mediated by protein kinase B. Surface expression of the
      epidermal growth factor (EGF)-receptor was reduced after PtdIns(3,4)P2-bv-sPLA2
      administration and associated with a blockade of EGF-induced signalling. In
      addition, mass spectroscopy revealed that bv-sPLA2 cleaves PtdIns(3,4)P2 to
      generate lyso-PtdIns(3,4)P2. In conclusion, we suggest that the cytotoxic
      activity mediated by PtdIns(3,4)P2 and bv-sPLA2 is due to cell death that results
      from disruption of membrane integrity, abrogation of signal transduction and the
      generation of cytotoxic lyso-PtdIns(3,4)P2.

PMID- 16947022
TI  - Induction of apoptosis and immune response by all-trans retinoic acid plus
      interferon-gamma in human malignant glioblastoma T98G and U87MG cells.
AB  - Glioblastoma is the most common and highly malignant brain tumor. It is also one
      among the most therapy-resistant human neoplasias. Patients die within a year of
      diagnosis despite the use of available treatment strategies such as surgery,
      radiotherapy, and chemotherapy. Thus, there is a critical need to find a novel
      therapeutic strategy for treating this disease. Here, we have investigated the
      molecular mechanisms for induction of apoptosis as well as for activation of
      immune components in human malignant glioblastoma T98G and U87MG cells following
      treatment with all-trans retinoic acid (ATRA) plus interferon-gamma (IFN-gamma).
      Treatment of glioblastoma cells with ATRA alone prevented cell proliferation and
      induced astrocytic differentiation, while IFN-gamma alone induced apoptosis and
      modulated expression of human leukocyte antigen (HLA) class II molecules such as
      HLA-DRalpha, HLA-DR complex, invariant chain (Ii), HLA-DM (an important catalyst
      of the class II-peptide loading), and gamma interferon-inducible lysosomal thiol
      reductase (GILT). Interestingly, both T98G and U87MG cells showed more increase
      in apoptosis with expression of the HLA class II components for an effective
      immune response following treatment with ATRA plus IFN-gamma than with IFN-gamma
      alone. Apoptotic mode of cell death was confirmed morphologically by Wright
      staining and biochemically by measuring an increase in caspase-3 activity. While
      conversion of tumor cells into HLA class II+/Ii- cells by stimulation with the
      helper CD4+ T cells is thought to be challenging, this study reports for the
      first time that treatment of glioblastoma cells with ATRA plus IFN-gamma can
      simultaneously enhance apoptosis and expression of the HLA class II immune
      components with a marked suppression of Ii expression. Taken together, this study
      suggests that induction of apoptosis and immune components of the HLA class II
      pathway by ATRA plus IFN-gamma may be a promising chemoimmunotherapeutic strategy
      for treatment of human malignant glioblastoma.

PMID- 16947023
TI  - HLA-A0201 positive pancreatic cell lines: new findings and discrepancies.
AB  - Pancreatic cancer is being pursued as an immunotherapy target using antigen
      specific vaccine approaches activating CD8(+) CTL and CD4(+) T-helper cells.
      CD8(+) CTL exert their anti-tumor effects in an HLA-restricted manner and only
      tumor cells carrying a matched HLA class I sub-type are targets for antigen
      specific CTL. In the process of characterizing CD8(+) T cell responses against
      pancreatic cancer, we screened a number of human pancreatic tumor cell lines for
      HLA-A0201 positive (HLA-A2(+)) cell lines to be used in the evaluation of CTL
      function. This analysis revealed some new findings and discrepancies in the
      literature on the HLA sub-type of some commonly used pancreatic cell lines. We
      found that Capan-1 cells, originally reported to be HLA-A0201(+), actually only
      express HLA-A010101 and HLA-A300101 and were targets for HLA-A0201-restricted CTL
      only after transduction with an HLA-A0201-expressing lentivirus. Panc-1 cells
      were found to be HLA-A0201 positive, in agreement with published reports, while
      CF-Pac-1 cells were found to express both HLA-A020101 and HLA-A030101. We also
      found a normal human pancreatic ductal epithelial cell line, HPDE, to be HLA
      A0201 positive. Our findings were verified with two different sequence-based
      typing methods, antibody staining followed by flow cytometry analysis, and
      functional analysis using an HLA-A0201-restricted peptide-specific T cell
      response.

PMID- 16947024
TI  - Ingestion of unusual foreign bodies and malrotation: a "perfect storm".
AB  - Management of foreign body ingestion is usually nonsurgical unless atypical
      foreign bodies or anatomical variants are suspected. The present article
      illustrates a case of atypical foreign bodies ingestion in the presence of
      intestinal malrotation. The patient required surgical treatment and had an
      uneventful postoperative recovery. The article also reviews the cases reported in
      the literature of magnetic ingestion and the possible complications associated
      with it.

PMID- 16947025
TI  - Experience with choledochal cysts in infants.
AB  - The purpose of this analysis is to study the clinical features, liver histology
      and the outcome after surgery in infants with choledochal cysts (CDCs), and to
      draw conclusions on the management strategy accordingly. The clinical features,
      liver histology and the outcome after surgery in 14 cases of CDCs treated before
      1 year of age (the "infantile group") were compared with 52 cases that were
      diagnosed and treated between 1 and 12 years of age (the "classical pediatric
      group"). The differentiation of the "infantile choledochal cysts" from "biliary
      atresia with cystic dilatation" was based on the configuration of intrahepatic
      bile ducts on cholangiogram. Jaundice was the universal presenting feature in 14
      patients in the "infantile group", the clinical presentation in 6 infants was
      indistinguishable from biliary atresia. On the other hand, pancreatitis as a
      presenting complication was seen exclusively in those presenting later, i.e. the
      "classical pediatric group". Fibrosis, as early as 4 weeks of age, was seen in
      all nine (100%) infants in whom a liver histology was available. Seven of these
      nine infants had bridging fibrosis (n = 4) or cirrhosis (n = 3) on liver
      histology. The outcome was satisfactory in 9 of the 14 (64.3%) infants despite
      bridging fibrosis (n = 4) or cirrhosis (n = 1) in 5 of these 9 babies. The CDCs
      presenting in infancy differ from the classical variety of later presenting
      pediatric CDCs in terms of their presentation, liver histology and outcome. They
      merit an emergent surgical treatment following which the outcome is satisfactory.
      Delay results in progression to end stage liver disease.

PMID- 16947026
TI  - A comparison of free skin graft, fascia lata, alloderm, bovine pericardium and
      primary repair in urethrocutaneous fistulas without diversion: an experimental
      study.
AB  - The purpose of this study is to compare primary repair procedure with those that
      use bio-concordant materials in the treatment of urethrocutaneous fistula. Twenty
      five New Zealand rabbits were randomly placed into five groups (primary repair,
      free graft, allograft fascia lata, alloderm and bovine pericardium repair
      groups). A single dose of 20 mg/kg of ceftriaxon was applied intramuscularly as a
      prophylactic dose. Urethrocutaneous fistula was formed on midpenile level. Later,
      while primary repair was applied in one group, repair with free grafts and with
      other bio-concordant materials were performed in other groups. Urinary diversion
      was not used in any of the rabbits. The macroscopic observation was evaluated
      with urethrography obtained 21 days after the operation and then the rabbits were
      sacrificed. A total point was obtained by awarding a point to each good parameter
      in the histopathological evaluation and all the groups were compared. The
      urethrographic findings and macroscopic examinations were normal in all groups.
      In histopathological examinations, ranging from the best to worst results, bovine
      pericardium group (8 points) had a better total score than primary repair group
      (7 points), allograft fascia lata group (7 points) and alloderm group (7 points).
      The free graft group had the worst total point (6 points). Bio-concordant
      materials can be used in urethrocutaneous fistula repair as an alternative to
      primary repair or to the grafts obtained from body tissues.

PMID- 16947027
TI  - A prospective study into the demographics and treatment of paediatric facial
      lacerations.
AB  - To evaluate the demographics and treatment of facial lacerations occurring in a
      paediatric patient cohort. We undertook a prospective study of 106 children who
      sustained a soft tissue facial injury and who presented to an Accident and
      Emergency department in a UK district general hospital supporting a population of
      750,000. Approximately 31,000 are dependent children between the age of 0-12
      years. Our results show that the majority of paediatric patients who sustained a
      facial laceration were male (62%). The frequency of this injury was greatest
      amongst males across all age groups. The majority of children above 3 years of
      age sustained their injury outdoors. The peak time for injury varied for
      different age groups. The 0-3 year olds sustained the highest incidence of
      injuries around 17:00 h. A bi-modal time pattern was seen in the 4-6 year age
      group, initially at 12:00 h with a second peak at 17:00 h. The most frequent
      aetiology was play. A significant finding was that 8% of the injuries that were
      managed resulted from a dog bite. Almost 50% of children above 4 years of age,
      who required primary closure of their laceration, were able to tolerate their
      treatment being performed under local anaesthesia. The pattern of facial
      lacerations in our study supports the results of previous studies. Our data has
      provided further insight into the presentation of these injuries. These studies
      are valuable in targeted injury prevention programmes aimed at potentially
      reducing the nature, incidence and severity of facial soft tissue trauma in
      children in the UK.

PMID- 16947028
TI  - Congenital adrenal hyperplasia: long-term evaluation of feminizing genitoplasty
      and psychosocial aspects.
AB  - Analyzing the long-term outcome in females with congenital adrenal hyperplasia
      (CAH) is crucial to evaluate effectiveness of treatment strategies. The aim of
      the study was to evaluate the long-term results in patients with CAH after
      feminizing surgery from the pediatric intersex clinic. Of 163 patients of CAH
      being followed (1980-2005), 50 responded for review. The patients had undergone
      feminizing genitoplasty and hormonal therapy. Evaluation included filling a
      detailed questionnaire along with physical examination and a structured interview
      in privacy. Assessment was performed for cosmetic results (50), psychosocial
      adjustment (42) above 5-year age, and functional outcome in 19 cases above 14
      year age. Mean age at clitoroplasty was 3.6 years (1-16 years) and at time of the
      study was 14.6 years (4-23 years), with a mean post-op follow up of 6 years after
      the final surgery (6 months-17 years). The cosmetic outcome of clitoroplasty was
      excellent in 37, satisfactory in 10, and poor in 3. Gender identity was female,
      male, and mixed in 45, 4, and 1, respectively. The attitude to self and life was
      positive in 36 and negative in 6. The functional outcome of vaginoplasty was
      satisfactory, unsatisfactory, and undetermined in 11, 4, and 4, respectively.
      Endocrine control was satisfactory in 36/50. A novel assessment system has been
      adopted for analyzing the results of clitoroplasty and vaginoplasty. Endocrine
      control and surgical treatment are complimentary to each other to achieve
      satisfactory results in majority of CAH patients.

PMID- 16947029
TI  - Clinical quiz. A patient with recurrent episodes of red urine.

PMID- 16947030
TI  - Idiopathic hypercalciuria in infants with renal stones.
AB  - In children older than 2 years, hypercalciuria is the most common metabolic cause
      of renal stones. In infants, its prevalence is not well established. Since 1990,
      we observed five infants in whom renal stones or microcalculi were diagnosed
      between the age of 5 and 19 months. One of them was lost to follow up. In the
      present report, we describe the four patients who underwent metabolic evaluation
      and in whom idiopathic hypercalciuria (IH) was diagnosed. We conclude that IH is
      a frequent cause of microcalculi and renal stones in infants, and a screen for
      this condition is warranted in this age group.

PMID- 16947031
TI  - Hyperuricemia and gout following pediatric renal transplantation.
AB  - Hyperuricemia and gout are common complications in adult renal transplant
      recipients. In pediatric recipients, however, hyperuricemia seems to be rare, but
      data are scarce. Thirty-two children (21 males, 11 females) were investigated for
      a median time of 4.8 years (range: 0.4-11.2 years) following renal
      transplantation. The median age of this pediatric study group was 13.9 years
      (range: 5.7-20.3 years), and the calculated glomerular filtration rate (GFR) was
      61 ml/min per 1.73 m(2) (range:12-88 ml/min per 1.73 m(2)). All patients were
      given calcineurin inhibitors, with 22 and ten children receiving cyclosporine A
      (CSA) and tacrolimus (TAC), respectively. The median plasma uric acid was 385
      micromol/l (range: 62-929 micromol/l); 15 children (47%) were above the age
      related normal range. Only one patient experienced gouty arthritis. There was a
      significant correlation between plasma uric acid concentration and both time span
      after transplantation and plasma creatinine, and an inverse correlation to GFR
      (p<0.05). No significant correlation was found between plasma uric acid and body
      mass index (BMI). Plasma uric acid concentrations were neither different among
      CSA- and TAC-treated children, nor did they correlate with drug exposure or blood
      trough levels of CSA or TAC. Plasma uric acid concentration was not different
      when compared to children with chronic renal failure (CRF) of a similar degree in
      native kidneys. We conclude that hyperuricemia is common among pediatric renal
      transplant recipients and rather a consequence of chronic renal transplant
      dysfunction than the use of calcineurin inhibitors. Gout, however, is rare.

PMID- 16947032
TI  - Essentials of laboratory medicine for the nephrology clinician.
AB  - The purpose of this review is to compile and bring to the attention of the
      pediatric nephrology community various aspects of laboratory medicine pertinent
      to nephrology. The review addresses different aspects in laboratory medicine that
      should be taken into account during interpretation of a test result, such as
      methodological and analytical issues, statistical considerations and the
      biological interpretation of a test result in the context of the clinical
      setting. An understanding of the considerations and limitations in laboratory
      medicine will be helpful to the pediatric nephrologist when ordering and
      interpreting biochemical tests.

PMID- 16947033
TI  - Crescentic glomerulonephritis is part of hyperimmunoglobulinemia D syndrome.

PMID- 16947034
TI  - [Surgical treatment of ileus. Differential diagnosis and therapeutic results].
AB  - Intestinal obstruction and ileus continue to represent a surgical challenge,
      regarding diagnosis and treatment. The decision when to operate is often
      difficult and should be based primarily on the clinical impression, although
      modern diagnostic tests are very helpful. Additionally, it is crucial to choose
      an operation that the patient can tolerate, as the spectrum of surgical
      interventions ranges from the taking-down of a single adhesion, that may be done
      laparoscopically, to sophisticated lysis of the intestine in patients with
      metastatic cancer in the peritoneal cavity, and simple diversion to extensive
      resections. These aspects are highly relevant, as good outcome can only be
      expected when the operation is performed correctly and optimal timing and
      appropriate choice of procedure are ensured.

PMID- 16947035
TI  - [Determinants of severely injured patients' trust in their hospital physicians].
AB  - BACKGROUND: Several studies have shown negative effects of insufficient physician
      patient interaction leading to a lack of compliance, worse subjective and
      objective evaluation of treatment outcome, increased consumption of pain
      medication, and decreased patient satisfaction. The aim of the present study was
      to identify patient-, physician-, and/or hospital-specific determinants which
      have a significant influence on the trust of severely injured patients in their
      physicians. METHODS: A written questionnaire was sent to 121 severely injured
      patients hurt predominantly in traffic accidents and treated between July 1996
      and July 2001 in two departments of surgery in the German state of Northrhine
      Westfalia. Applying the Total Design Method, a response rate of 74.4% (n=90)
      could be achieved. RESULTS: Using univariate analysis as a preselection tool, we
      developed a logistic regression model which identified four significant
      predictors of patients' trust in their physicians: (1) patient evaluation of
      information, (2) patient evaluation of their physician's decision policy, (3)
      patient evaluation of treatment success, and (4) patient age. CONCLUSIONS:
      Besides age of patient and subjective evaluation of treatment success, it is
      psychosocial aspects of interaction which influence trust in a physician. The
      results of this analysis confirm the importance of physician-patient
      communication for medical education, also for surgeons.

PMID- 16947036
TI  - [Perianal abscess and anal fistula in infancy and childhood. A congenital
      etiology?].
AB  - BACKGROUND: Perianal abscess and anal fistula in childhood are commonly treated
      in the same way as abscess and fistula in adults. We questioned whether they
      represent a cryptoglandular infection, as in adults, or two different diseases
      with the same symptoms. MATERIALS AND METHODS: We retrospectively analyzed all
      medical records of 80 children (seven male, 73 female) who underwent surgical
      treatment for primary perianal abscess or primary anal fistula during a 10-year
      period. The records were analyzed concerning age at appearance of lesion, sex,
      diagnosis (fistula and/or abscess), and anatomic localization of the lesion.
      RESULTS: Of all the children, 67.5% were treated during their 1st year of life
      and another 10% during their 2nd year (group 1: 77.5%, n=62). Only 22.5% were 3
      or older (group 2, n=18). Group 1 contained significantly more male infants (m:f
      30:1). However, much more balanced sex distribution was detected in group 2 (m:f
      2.6:1), similarly to adults. Analyzing anatomic localization, a second important
      difference could be found: in contrast to group 2, almost two thirds of all anal
      fistulas/abscesses in group 1 were localized horizontally between 3:00 and 9:00
      o'clock in crown-rump position. CONCLUSIONS: Divergences in preference of age,
      sex, and localization suggest a congenital etiology for anal fistulas and
      perianal abscesses in children.

PMID- 16947037
TI  - [Methods of imaging and bone densitometry in osteoporosis of patients with
      inflammatory rheumatoid diseases].
AB  - Besides clinical history and clinical findings conventional X-ray is important in
      the evaluation of osteoporosis as the third diagnostic tool. Its purpose is
      mainly excluding other diseases and proof of fractures as well as their follow
      up. Also X-ray is able to demonstrate complications of osteoporosis such as
      insuffiency fractures and effects of therapy as for example fluorosis. For very
      early diagnosis bone densitometry is used. Today the improved methods deliver
      fracture prediction percentages of high value. As a planar measurement method DXA
      of the spine and of the femoral neck can be used. Volumetric tools, which can
      measure trabecular bone, without overlying cortical bone, are computed tomography
      of the spine and of the distal radius. Quantitative ultrasound is an interesting
      approach, but which does not really measure bone densitometry and which is net
      yet suited for clinical follow up. Quantitative Magnetic Resonance is far from
      routine clinical application.

PMID- 16947038
TI  - [DVO guideline 2006. What changes have there been in the diagnosis, prevention
      and treatment of osteoporosis?].
AB  - The main changes in the updated DVO guideline 2006 on prevention, diagnosis and
      treatment of osteoporosis in postmenopausal women and in older men concern the
      evaluation of individual fracture risks and the selection of medicamentous
      therapy by means of new thresholds. A 30% risk of osteoporotic vertebral or hip
      fracture per decade is recommended as the threshold for implementation of
      pharmacological therapy. Evaluation of the individual absolute fracture risk is
      based on a combination of the results of densitometry at the lumbar spine and
      femur, age, gender, and other risk factors that are specifically associated with
      osteoporosis. Patient's mobility is assessed by carrying out special mobility
      tests. Further changes seen in the 2006 update of the DVO guideline are therapy
      proposals taking account of new pharmaceutical developments. New effective
      medications are rh-PTH (1-34), or teriparatide, strontium ranelate, and
      ibandronate (bisphosphonate) for monthly oral administration. Minimally invasive
      operative techniques for use in vertebral fractures in combination with
      medicamentous antiosteoporosis therapy are also included in the 2006 update of
      the DVO guideline. Thus, in the 2006 update of the DVO-guideline we have a
      practice-oriented 53 guideline that is adapted to individual fracture risk and
      gives recommendations on the prevention, diagnosis and treatment of osteoporosis.

PMID- 16947039
TI  - Reducing the unmet needs of patients with colorectal cancer: a feasibility study
      of The Pathfinder Volunteer Program.
AB  - GOALS OF THE WORK: Many cancer patients experience unmet needs and elevated
      levels of anxiety and depression. This paper describes a volunteer-delivered
      intervention to reduce the psychosocial needs of cancer patients and presents
      findings from a feasibility study of this intervention. MATERIALS AND METHODS:
      The telephone-based intervention, called the Pathfinder Program, involves the
      assignment of volunteers to patients to assist them in addressing their needs as
      identified in questionnaires. Fifty-two patients with colorectal cancer were
      involved in the feasibility study, with 18 in the intervention. Sixty-two percent
      of the sample was male and the mean age was 64 years. Patients' needs were
      assessed using The Supportive Care Needs Survey, a colorectal cancer symptom
      checklist, and the Hospital Anxiety and Depression Scale. All patients completed
      baseline questionnaires (Time 1) and 47 completed Time 2 questionnaires 3 months
      later. MAIN RESULTS: The most common needs were fear of the cancer spreading and
      returning, concerns about the worries of others, gas or wind, changes in weight,
      and bowel problems such as diarrhea, constipation, and pain. A statistically
      significant Time 1 to Time 2 decrease in supportive care needs and depression was
      found for the intervention group. CONCLUSIONS: The Pathfinder Program has been
      found to be feasible, acceptable for patients, and has the potential to reduce
      needs and depression. A larger, randomized controlled trial is needed to
      determine the impact of this program on colorectal symptoms and anxiety.

PMID- 16947040
TI  - Novel organization of catechol meta pathway genes in the nitrobenzene degrader
      Comamonas sp. JS765 and its evolutionary implication.
AB  - The catechol meta cleavage pathway is one of the central metabolic pathways for
      the degradation of aromatic compounds. A novel organization of the pathway genes,
      different from that of classical soil microorganisms, has been observed in
      Sphingomonas sp HV3 and Pseudomonas sp. DJ77. In a Comamonas sp. JS765, cdoE
      encoding catechol 2,3-dioxygenase shares a common ancestry only with tdnC of a
      Pseudomonas putida strain, while codG encoding 2-hydroxymuconic semialdehyde
      dehydrogenase shows a higher degree of similarity to those genes in classical
      bacteria. Located between cdoE and cdoG are several putative genes, whose
      functions are unknown. These genes are not found in meta pathway operons of other
      microorganisms with the exception of cdoX2, which is similar to cmpX in strain
      HV3. Therefore, the gene cluster in JS765 reveals a third type of gene
      organization of the meta pathway.

PMID- 16947041
TI  - HER-2/neu overexpression is an independent prognostic factor in colorectal
      cancer.
AB  - BACKGROUND AND AIMS: The HER-2/neu protein is intimately involved with normal
      cell proliferation and tissue growth, as it is extensively homologous and is
      related to the epidermal growth factor receptor. This phenomenon has been most
      intensively studied in the context of breast carcinoma, in which its
      amplification and overexpression correlate with the overall course of disease and
      poor prognoses, and also constitute a predictive factor of poor response to
      chemotherapy and endocrine therapy. In this study, we investigated the
      relationships between the expression of HER-2/neu and the clinicopathological
      characteristics of colorectal cancer, including survival. This study was
      performed with a view toward the future introduction of Herceptin therapy for
      colorectal cancer patients. PATIENTS AND METHODS: HER-2/neu overexpression and
      gene amplification were examined via semiquantitative standardized
      immunohistochemical staining and fluorescence in situ hybridization (FISH) in 137
      colorectal cancer patients who underwent curative surgery at the Kangbuk Samsung
      Hospital. RESULTS: Sixty-five (47.4%) out of 137 patients were determined by
      immunohistochemistry to have overexpressed HER-2/neu protein. HER-2/neu gene
      amplification was detected in two patients by FISH. Tumors with HER-2/neu
      overexpression showed higher postoperative recurrence rate (39.3% vs 14.6%,
      p=0.013). Tumors with HER-2/neu overexpression were associated with poor 3-year
      (70.8% vs 83.7%) and 5-year survival rates (55.1% vs 78.3%, p<0.05). Advanced TNM
      stage, postoperative recurrence, and overexpression of HER-2/neu were found to be
      independently related to survival by multivariate analysis. CONCLUSION: HER-2/neu
      overexpression may constitute an independent prognostic factor in colorectal
      cancer patients, and patients exhibiting HER-2/neu overexpression might
      constitute potential candidates for a new adjuvant therapy which involves the use
      of humanized monoclonal antibodies.

PMID- 16947042
TI  - The survival rate and prognostic factors in 26 perforated colorectal cancer
      patients.
AB  - PURPOSE: The treatment for perforated colorectal cancer is not easy and the
      prognosis for this disease is not so predictable. There are some controversies
      about performing radical operations because colorectal cancer perforation was
      considered as an advanced stage disease due to the possibility of tumor cell
      dissemination through the perforation site. METHODS: We selected and enrolled 26
      patients with perforated colorectal cancers among the 1,227 patients who
      underwent operation for colorectal cancer. These cases were retrospectively
      analyzed by using their medical records and clinicopathological data. RESULTS:
      Twenty-eight cases (2.3%) with perforated colorectal cancers were studied and the
      overall operative mortality rate was 11%. The overall 5-year survival rate was
      57.8% when excluding the operative mortality. The overall 5-year cancer-free
      survival rate was 52.8%. There were significant differences in the survival rate
      and the cancer-free survival rate between the stages (p=0.008 and p<0.001,
      respectively). A univariate analysis of the prognostic factors revealed that the
      number of the metastatic lymph nodes (p=0.018) and the perforation proximal to
      the cancer (p=0.005) were significantly correlated to worse survival, and the
      higher number of the metastatic lymph nodes was correlated to a poorer cancer
      free survival rate (p<0.001). CONCLUSION: For the perforated colorectal cancers,
      the stage, the perforation proximal to the cancer, and the number of the
      metastatic lymph nodes were correlated, with the survival and the cancer-free
      survival as factors of a poor prognosis. The surgical approach selected for
      perforated colorectal cancer should be in line with the principles of an
      appropriate cancer operation because the clinical pathway of perforated
      colorectal cancer is similar to that of uncomplicated colorectal cancer.

PMID- 16947043
TI  - Accessory costs of seed production.
AB  - Accessory costs of reproduction are those that are necessary to mature a seed,
      but that do not involve the direct cost of provisioning the seed itself. This
      study aims to quantify accessory costs in a range of species, and test whether
      they decrease as a proportion of total reproductive expenditure with increasing
      seed mass, as might be expected if economies of scale came into play at larger
      seed sizes. We also test whether accessory costs varied with growth form,
      pollination mode, and dispersal mode, with the expectation that biotic
      pollination and dispersal modes should incur greater costs. Reproductive
      allocation (dry biomass) over one season, was calculated for 14 diclinous
      angiosperm species. Accessory costs averaged 73% of total reproductive
      allocation, with the majority spent on packaging and dispersal. Total accessory
      costs, packaging and dispersal costs, and costs incurred prior to pollination
      were proportional to direct costs of reproduction in major axis regressions.
      However, larger seeded species incurred significantly greater costs associated
      with aborted seeds and fruits, and matured a smaller proportion of ovules. This
      is consistent with larger seeded species being more selective of the
      ovules/embryos matured than small-seeded species. Total accessory costs, and
      proportion of ovules aborted, were also significantly greater for biotically
      dispersed species, but only due to an association with larger seed masses. Costs
      associated with abortions were lower for biotically pollinated species, due to a
      general trend of more ovules per ovary, resulting in greater cost sharing. This
      study demonstrates that expenditure on items other than seeds accounts for the
      majority of reproductive allocation in flowering plants. Yet, far more literature
      exists on seed mass variation than on investment in accessory structures. We
      found a proportional relationship between accessory costs and seed mass that
      warrants further investigation within the context of selection on margin returns
      on investment.

PMID- 16947044
TI  - Mutation profile of EGFR gene detected by denaturing high-performance liquid
      chromatography in Japanese lung cancer patients.
AB  - PURPOSE: EGFR mutations in lung cancer increase sensitivity to an EGFR tyrosine
      kinase inhibitor, gefitinib. Mutation analysis of EGFR is essential for
      prediction of gefitinib response and avoidance of the coincidental severe side
      effects for the unresponsive population. The purpose of the present study is to
      apply DHPLC as a screening system of detection of EGFR mutations for large scaled
      population. METHODS: EGFR mutations were detected by both DHPLC procedure and
      direct sequencing using lung cancer tissue samples obtained from 97 patients (81
      surgical specimens and 16 pleural effusions of non-resectable lung cancer
      patients). RESULTS: DHPLC analysis detected EGFR mutations in 5 h as opposed to
      18 h by direct sequencing for ten samples, and it costs eightfold more expensive
      by direct sequencing than DHPLC. In addition, DHPLC analysis was sixfold more
      sensitive than sequencing analysis for detection of the point mutation of exon
      21, L858R. Using this system, EGFR mutations in exons 18, 19 and 21 were found in
      34 of 97 patients (36%). Thirteen of the 15 patients with exon 21 mutations (87%)
      were female non-smokers, who were diagnosed with adenocarcinomas with the feature
      of BAC. Eight of the 18 patients with exon 19 mutations (44%) were 7 male and 1
      female current or former smokers, and BAC feature was observed in 61% (8/18).
      CONCLUSION: DHPLC analysis for screening followed by sequencing analysis appears
      to be more sensitive and accurate, as well as easier and faster. In addition,
      these results suggest different mutagenesis and carcinogenesis pathways for
      mutations.

PMID- 16947045
TI  - [Perioperative administration of beta-blockers. Critical appraisal of recent meta
      analyses].
AB  - BACKGROUND: The perioperative administration of beta blockers is a controversial
      issue. Numerous trials failed to show any significant benefit or disadvantage
      because of low event rates and insufficient statistical power. METHODS: In July
      2005 McGory et al. and Devereaux et al. separately published 2 meta-analyses,
      raising the question of the perioperative administration of beta blockers for
      patients undergoing non-cardiac surgery. In February 2006, Schouten et al.
      published an additional meta-analysis concerning the same question. This evidence
      is supplemented by the publication of Lindenauer et al. in 2005. These trials
      will be critically appraised in this review. RESULTS: McGory et al. concluded
      from their data that the perioperative administration of beta blockers
      significantly reduced cardiovascular mortality. However, this conclusion is
      clearly not valid because of methodological deficits of the meta-analysis. In
      addition, the publications by Devereaux et al. and Schouten et al. did not
      support the results of the analysis by McGory et al. CONCLUSIONS: There is still
      no clear evidence to prove a significant benefit for the unselected perioperative
      use of beta blockers in patients undergoing non-cardiac surgery. While high-risk
      patients and those undergoing major surgical procedures seem to profit, low-risk
      patients may be more harmed than helped by this intervention. The fact that 3
      meta-analyses raising the same question produced substantially different results,
      underlines the importance of critically appraising each meta-analysis.

PMID- 16947046
TI  - In vivo occupancy of dopamine D2 receptors by antipsychotic drugs and novel
      compounds in the mouse striatum and olfactory tubercles.
AB  - Interaction with dopamine D2-like receptors plays a major role in the therapeutic
      effects of antipsychotic drugs. We examined in vivo dopamine D2 receptor
      occupancy of various established and potential antipsychotics in mouse striatum
      and olfactory tubercles 1 h after administration of the compound, using
      [3H]nemonapride as a ligand. All the compounds reduced in vivo binding of
      [3H]nemonapride in the striatum. When administered systemically, conventional
      antipsychotics, D2 antagonists, nemonapride (ID50: 0.034 mg/kg), eticlopride
      (0.047), haloperidol (0.11) and raclopride (0.11) potently inhibited
      [3H]nemonapride binding. The 'atypical' antipsychotics, risperidone (0.18),
      ziprasidone (0.38), aripiprazole (1.6), olanzapine (0.99), and clozapine (11.1)
      were less potent for occupying D2-like receptors. New compounds, displaying
      marked agonism at 5-HT1A receptors in addition to D2 receptor affinity, exhibited
      varying D2 receptor occupancy: bifeprunox (0.25), SLV313 (0.78), SSR181507 (1.6)
      and sarizotan (6.7). ID50 values for inhibition of [3H]nemonapride binding in the
      striatum correlated with those in the olfactory tubercles (r=0.95, P<0.0001).
      These values also correlated with previously-reported in vitro affinity of the
      compounds at rat D2 receptors (r=0.85, P=0.0001) and with inhibition of
      apomorphine-induced climbing in mice (r=0.79 P=0.0005). In contrast, there was no
      significant correlation between ID50 values herein and previously-reported ED50
      values for catalepsy in mice. These data indicate that: (1) there is no
      difference in D2 receptor occupancy in limbic versus striatal regions between
      most classical and atypical or potential antipsychotics; and (2) high occupancy
      of D2 receptors can be dissociated from catalepsy, if the drugs also activate 5
      HT1A receptors. Taken together, these data support the strategy of simultaneously
      targeting D2 receptor blockade and 5-HT1A receptor activation for new
      antipsychotics.

PMID- 16947047
TI  - Wandering chordoma--a mid-line crisis?

PMID- 16947048
TI  - Closed suction drains do not increase the blood transfusion rates in patients
      undergoing total knee arthroplasty.
AB  - We aim to determine whether the presence of a drain increases the actual blood
      transfusion rates in patients undergoing primary total knee arthroplasty (TKA). A
      retrospective review was performed on two consecutive groups of patients who
      underwent primary TKA: group 1 including 100 patients who underwent TKA and had
      one deep closed suction drain; group 2 including 100 patients who underwent TKA
      and had no drain. Blood transfusions were given post-operatively on the basis of
      clinical need without a pre-determined haemoglobin trigger factor. Group 1
      drained a mean of 692 ml (range 150-1500) of blood in 48 h. The mean fall in
      haemoglobin at 48 h post-operatively was 3.26 g/dl in group 1 and 3.33 g/dl in
      group 2. Nine patients in group 1 and seven patients in group 2 required a blood
      transfusion; this was not statistically significant (P=0.79). Transfusion of
      primary TKA patients on the basis of clinical need can result in post-operative
      transfusion rates of 8%. The presence of a drain does not increase the
      transfusion rates of patients undergoing primary TKA.

PMID- 16947049
TI  - Smoking increases failure rate of operation for established non-union of the
      scaphoid bone.
AB  - The aim of the study was to investigate the effect of smoking on the operative
      treatment of established non-union of the carpal scaphoid. Case notes and
      radiographs of patients undergoing bone grafting and screw fixation of scaphoid
      non-unions were reviewed. There were 34 patients that had undergone 37 operations
      for established non-union of the carpal scaphoid bone. There were two female
      patients, and the average age was 26.8 years (range 13.4 years to 52.9 years).
      The median delay to operation was 11.9 months. The overall success rate of the
      operation (internal fixation and autologous bone grafting) was 59.5% (22/37), but
      there was a significant association between non-union and smoking (P=0.02 for
      Fisher's exact test). In non-smokers (n=17) the success rate was 82.4%, but this
      dropped to 40.0% among smokers (P<0.01). We concluded that smoking was
      significantly associated with failure of operative treatment of established non
      union of the scaphoid bone.

PMID- 16947050
TI  - Effects of screw eccentricity on the initial stability of the acetabular cup.
AB  - One of the major failure modes of cementless acetabular components is the
      loosening of the acetabular cup, which is mostly attributable to insufficient
      initial stability. A hemispherical cup with a porous coating which is inserted
      with press-fit fixation and secured with several screws is one of the most widely
      used approaches. Many studies have found that bone screws are very helpful aids
      for cup fixation, but the optimal surgical technique for inserting screws has not
      been clearly reported. In this study, hemispherical cups were fixed into blocks
      of foam bone with zero to three screws. The effects of three types of screw
      eccentricity (a 1-mm offset and angular eccentricities of 15 degrees and 25
      degrees ) on the initial stability of the acetabular cup were evaluated. The
      experimental results indicate that increasing the number of screws enhances the
      cup stability in the case of ideal screwing (i.e., with no eccentricity). An
      angular eccentricity of 15 degrees did not affect the cup stability for fixation
      with one or two screws. However, the presence of 25 degrees of angular
      eccentricity significantly reduced the stability of the cup, while 1 mm of offset
      eccentricity produced an even greater impact.

PMID- 16947051
TI  - The functional outcome of total tears of the anterior cruciate ligament (ACL) in
      the skeletally immature patient.
AB  - Tears of the anterior cruciate ligament (ACL) in the skeletally immature patient
      are becoming more prevalent. The aim of this study was to describe the functional
      outcome and to evaluate the best management of total tears of the ACL in
      skeletally immature patient. Twenty consecutive, skeletally immature patients
      with a clinically evident rupture of the anterior cruciate ligament were followed
      up for a mean of 5.4 years. The mean age at the time of injury was 13.9 years
      old. The study group consisted of 13 girls and 7 boys, who were treated either
      conservatively, by ACL reconstruction, by primary repair or by delayed ACL
      reconstruction after skeletal maturity had been reached. Clinical outcomes were
      measured using the International Knee Documentation Committee Scoring System
      (IKDC) and the Knee Injury and Osteoarthritis Outcome Scoring System (KOOS). The
      radiological evaluation was performed using Jaeger and Wirth's criteria, and
      instrumented laxity testing was carried out with a Rolimeter. Five of the eight
      patients treated conservatively showed poor function of the knee, and this
      resulted in instability. Concerning the patients treated by primary repair,
      delayed ACL reconstruction or arthroscopic debridement, we also found none of the
      results to be satisfactory (seven of eight patients). The patients that were
      treated by a reconstruction had the best results. This was confirmed by clinical
      examination (Lachmann grade 1), by the IKDC (grade B) and by the KOOS with the
      best quality of life and no giving-way attacks. The level of evidence was
      therapeutic level III.

PMID- 16947052
TI  - Less is more: lag screw only fixation of lateral malleolar fractures.
AB  - Displaced fractures of the lateral malleolus are typically treated with plate
      osteosynthesis with or without the use of lag screws, and immobilisation in a
      plaster cast for up to 6 weeks. Fixation through a smaller incision with less
      metal, such as lag screw only fixation, would theoretically lead to decreased
      infection rates and less irritation caused by hardware. The purpose of this study
      was to evaluate the benefits and success of lag screw only fixation of the
      lateral malleolus in non-comminuted oblique fractures of the lateral malleolus. A
      total of 25 patients who had non-comminuted unstable oblique fractures of their
      lateral malleolus that had been surgically fixed with lag screws only were
      retrospectively evaluated. All patients were younger than 60 years of age.
      Evaluation of the success of fixation, complications, resultant mobility and
      patient satisfaction was based on information gathered from chart reviews, X-ray
      findings and a standardised questionnaire based on the AOFAS Foot and Ankle
      Outcomes Questionnaire. These results were compared to an age-matched group of 25
      consecutive patients treated with plate osteosynthesis. Of the 25 patients fixed
      with lag screws, nine had an unstable fracture of the lateral malleolus only, ten
      were bimalleolar fractures and six were trimalleolar. Eighteen patients were
      treated with two lag screws, and seven were treated with three lag screws. The bi
      and trimalleolar fractures were treated with standard partially threaded
      cancellous screws. None of the lag screw-only group lost reduction. There were no
      documented wound infections in the lag screw group as compared to three deep
      infections in the plate group. Lag screw-only patients reported no palpable
      hardware as compared to 50% of the plate group. AOFAS scores at a mean of 12
      months post-operative were similar in both groups. Lag screw only fixation of the
      lateral malleolus is a safe and effective method that has a number of advantages
      over plate osteosynthesis, in particular less soft tissue dissection, less
      prominent, symptomatic and palpable hardware and a reduced requirement for
      secondary surgical removal.

PMID- 16947053
TI  - To detach the long head of the biceps tendon after tenodesis or not: outcome
      analysis at the 4-year follow-up of two different techniques.
AB  - The aim of this study was to determine whether or not detaching the biceps tendon
      from the glenoid after tenodesis performed with the inclusion of the biceps in
      the rotator cuff suture results in an improved outcome. From 1999 to 2001, 22
      patients had an arthroscopic rotator cuff repair and associated biceps tendon
      lesions that were repaired with two new arthroscopic techniques of tenodesis
      incorporating the biceps tendon in the rotator cuff suture. Patients were
      randomised into one of two groups: tenodesis without tenotomy (group 1) and
      tenodesis with tenotomy (group 2). Preoperative and postoperative functions were
      assessed by means of a modified UCLA rating scale and shoulder ROM. The mean
      follow-up period was 47.2 months (range 36- 59). In group 1 (tenodesis without
      tenotomy), eight patients had an excellent postoperative score and three a good
      postoperative score. The UCLA rating system used for evaluation showed a
      statistically significant improvement from the preoperative average rating of
      10.5 (5-15) to the postoperative average score of 33 (29-35) (P<0.05). In group 2
      (tenodesis with tenotomy), the UCLA rating system used for evaluation showed a
      statistically significant improvement from the preoperative rating of 11.1 to the
      postoperative score of 32.9 (P<0.05). No statistically significant difference in
      the total UCLA scores was found when comparing the repairs performed with or
      without tenotomy. Follow-up results with regard to ROM were not different between
      the two groups, and the range of motion was improved in all measured directions.
      In this series, every patient qualified as having good to excellent results
      according to the UCLA score. This study suggests that there is no difference
      between detaching and not detaching the biceps after including it in the repair.

PMID- 16947055
TI  - Primary retroperitoneal non-Hodgkin lymphoma presenting with torturous
      generalized pruritus in an elderly.
AB  - INTRODUCTION: A case of a rare primary retroperitoneal non-Hodgkin lymphoma
      (NHL), which presented with torturous generalized pruritus in a 74-year-old
      female patient is reported METHODS: Case report. RESULTS: Explorative laparotomy
      was performed after imaging revealed a pelvic mass and an ovarian tumour was
      suspected. After the frozen section revealed a lymphoma, extensive surgery was
      omitted. The patient was successfully treated with courses of Bleo-CHOP regimen
      (complete response) and pruritus resolved entirely after completing the second
      course of chemotherapy. CONCLUSION: This report indicates the need of thorough
      investigation of the peritoneal cavity for the presence of NHL in cases
      presenting as unexplained pruritus in the elderly. In this setting the presence
      of a retroperitoneal pelvic mass must raise the suspicion for the possibility of
      the rare retroperitoneal NHL.

PMID- 16947054
TI  - Isolation and characterization of a novel v-SNARE family protein that interacts
      with a calcium-dependent protein kinase from the common ice plant,
      Mesembryanthemum crystallinum.
AB  - McCPK1 (Mesembryanthemum crystallinum calcium-dependent protein kinase 1) mRNA
      expression is transiently salinity- and dehydrationstress responsive. The enzyme
      also undergoes dynamic subcellular localization changes in response to these same
      stresses. Using the yeast-two hybrid system, we have isolated and characterized a
      M. crystallinum CPK1 Adaptor Protein 2 (McCAP2). We show that McCPK1 interacts
      with the C-terminal, coiled-coil containing region of McCAP2 in the yeast two
      hybrid system. This interaction was confirmed in vitro between the purified
      recombinant forms of each of the proteins and in vivo by coimmunoprecipitation
      experiments from plant extracts. McCAP2, however, was not a substrate for McCPK1.
      Computational threading analysis suggested that McCAP2 is a member of a novel
      family of proteins with unknown function also found in rice and Arabidopsis.
      These proteins contain coiled-coil spectrin repeat domains present in the
      syntaxin super-family that participate in vesicular and protein trafficking.
      Consistent with the interaction data, subcellular localization and fractionation
      studies showed that McCAP2 colocalizes with McCPK1 to vesicular structures
      located on the actin cytoskeleton and within the endoplasmic reticulum in cells
      subjected to low humidity stress. McCAP2 also colocalizes with AtVTIl1a, an
      Arabidopsis v-SNARE [vesicle-soluble N-ethyl maleimide-sensitive factor (NSF)
      attachment protein (SNAP) receptor] present in the trans-Golgi network (TGN) and
      prevacuolar compartments (PVCs). Both interaction and subcellular localization
      studies suggest that McCAP2 may possibly serve as an adaptor protein responsible
      for vesicle-mediated trafficking of McCPK1 to or from the plasma membrane along
      actin microfilaments of the cytoskeleton.

PMID- 16947056
TI  - Septic abortion: a review of social and demographic characteristics.
AB  - Septic abortion is a significant health problem with short- and long-term
      complications that affect the quality of life of those fortunate enough to avoid
      mortality. Both spontaneous and induced abortion can result in septic
      complications, with the latter disproportionately higher. Its incidence is high
      in environments with restrictive abortion laws, as clandestine procedures by non
      doctors in unhygienic settings are prevalent. This study shows that it is still
      more common among teenagers and mainly performed by health professionals, which
      means that health care interventions should be re-evaluated and appropriately
      directed to preserve the reproductive health status of this vulnerable
      population.

PMID- 16947057
TI  - Lead poisoning as a result of infertility treatment using herbal remedies.
AB  - INTRODUCTION: Lead poisoning remains a major problem in our society due to the
      lack of awareness of its ill effects among the clinical community. The non
      availability of blood lead levels at primary health centers results in many lead
      poisoned cases being treated symptomatically, without the diagnosis being sought.
      CASE REPORT: We report a case here, presenting with colicky abdominal pain
      receiving symptomatic treatment initially; lead poisoning was confirmed following
      the estimation of blood lead levels. DISCUSSION: The consumption of unbranded
      herbal medicines as a causative factor for lead poisoning was confirmed by high
      lead content in the medicines. Surely, this demands public health programs to
      disseminate strategies to the medical personnel about the clinical implication of
      lead poisoning, as well as the general public for awareness and to prevent lead
      poisoning.

PMID- 16947058
TI  - Prevalence of uterine defects in habitual abortion patients attended on at a
      university health service in Brazil.
AB  - OBJECTIVES: Assessment of the prevalence and types of uterine defects in patients
      with recurrent pregnancy loss (RPL) through hysteroscopy (HTC). PATIENTS AND
      METHODS: Sixty non pregnant patients with history of three or more consecutive
      spontaneous abortions were evaluated through HTC. The findings were separated
      into three groups: synechias, polypoids lesions (endometrial polyps and submucous
      myomas), and alterations of the cavity shape (mullerian anomalies). The findings
      were gathered and tabulated according to the presence of each defect. RESULTS:
      Uterine anomalies were observed in 23 (38.3%) patients, with 16 (26.7%)
      synechias, 3 (5.0%) polypoids lesions and 8 (13.3%) shape alterations.
      CONCLUSIONS: The results obtained here suggest that the uterine factor has high
      prevalence in patients with a RPL history, and for this reason it should be
      systematically assessed in patients with a RPL history.

PMID- 16947059
TI  - Tall fescue genomic SSR markers: development and transferability across multiple
      grass species.
AB  - Simple sequence repeat (SSR) markers are highly informative and widely used for
      genetic and breeding studies. Currently, a very limited number of SSR markers are
      available for tall fescue (Festuca arundinacea Schreb.) and other forage grass
      species. A tall fescue genomic library enriched in (GA/CT)( n ) repeats was used
      to develop primer pairs (PPs) flanking SSRs and assess PP functionality across
      different forage, cereal, and turf grass species. A total of 511 PPs were
      developed and assessed for their utility in six different grass species. The
      parents and a subset of a tall fescue mapping population were used to select PPs
      for mapping in tall fescue. Survey results revealed that 48% (in rice) to 66% (in
      tall fescue) of the PPs produced clean SSR-type amplification products in
      different grass species. Polymorphism rates were higher in tall fescue (68%)
      compared to other species (46% ryegrass, 39% wheat, and 34% rice). A set of 194
      SSR loci (38%) were identified which amplified across all six species. Loci
      segregating in the tall fescue mapping population were grouped as loci
      segregating from the female parent (HD28-56, 37%), the male parent (R43-64, 37%),
      and both parents (26%). Three percent of the loci that were polymorphic between
      parents were monomorphic in the pseudo F1 mapping population and the remaining
      loci segregated. Sequencing of amplified products obtained from PP NFFAG428
      revealed a very high level of sequence similarity among the grass species under
      study. Our results are the first report of genomic SSR marker development from
      tall fescue and they demonstrate the usefulness of these SSRs for genetic linkage
      mapping in tall fescue and cross-species amplification.

PMID- 16947060
TI  - Effects of intracerebroventricular injections of free fatty acids,
      lysophospholipids, or platelet activating factor in a mouse model of orofacial
      pain.
AB  - The present study was carried out to determine the effects of central nervous
      free fatty acids, lysophospholipids, or platelet activating factor (PAF), in a
      mouse facial carrageenan injection model of orofacial pain. Mice that received
      intracerebroventricular (I.C.V.) injection of arachidonic acid or oleic acid
      showed significantly reduced allodynia and behavioral responses to von Frey hair
      stimulation of a carrageenan-injected area of the face, at 8 h post-injection,
      compared to controls that received I.C.V. injection of vehicle. In contrast to
      free fatty acids, increased responses were observed in mice at 72 h after I.C.V.
      lysophosphatidic acid or lysophosphatidylcholine injection, and at 8 and 24 h
      after PAF injection, compared vehicle injected controls. Information regarding
      pro-nociceptive effect of specific brain lipids may be a useful basis for further
      studies to explore mechanism.

PMID- 16947061
TI  - Curvature discrimination in various finger conditions.
AB  - The ability of humans to discriminate curvature was investigated for different
      finger conditions. The experiments were conducted in which subjects explored
      cylindrically curved stimuli by touch. Using a 2-alternative forced-choice
      procedure, discrimination thresholds and biases were measured for several
      conditions. In 1-finger conditions, reference and test stimulus were explored
      with the same finger, whereas in 2-finger conditions these stimuli were felt with
      different fingers. Similar thresholds were obtained for the 1-finger conditions,
      in which either the preferred or the non-preferred index finger or the thumb was
      employed. However, significantly higher thresholds were found for the conditions
      in which subjects used two fingers, either of the same hand or of different
      hands. Interestingly, even higher thresholds were obtained for a 2-finger
      condition in which subjects explored the stimuli simultaneously instead of
      sequentially. In addition, subject-dependent biases were found in the 2-finger
      conditions. We conclude that the number of fingers and the mode of exploration
      have a considerable effect on performance in a haptic task such as curvature
      discrimination.

PMID- 16947062
TI  - Progressive suppression of intracortical inhibition during graded isometric
      contraction of a hand muscle is not influenced by hand preference.
AB  - GABAergic intracortical inhibition (ICI) in human motor cortex (M1) assists
      fractionated activation of muscles, and it has been suggested that hemispheric
      differences in ICI may contribute to hand preference. Previous studies of this
      issue have all been conducted at rest, with conflicting results. Testing during
      voluntary activation may reveal functionally relevant differences. In normal
      subjects, we assessed (1) operation of ICI circuits during selective activation
      of an intrinsic hand muscle at different forces, and (2) whether this differs
      between right and left hemispheres. Surface EMG was recorded bilaterally from
      abductor pollicis brevis (APB), first dorsal interosseous (FDI) and abductor
      digiti minimi (ADM) muscles in eleven right-handed subjects. A circular coil
      applied paired transcranial magnetic stimulation (TMS) with posteriorly directed
      current in the brain. Conditioning intensity was 0.8 x active threshold and
      interstimulus interval was 3 ms. TMS was applied to right or left M1 while
      subjects were at rest or performing isometric thumb abduction at different forces
      (0.5, 1, 2, 3, 5 and 10 N) with the contralateral hand. Conditioning TMS was less
      effective at suppressing the muscle evoked potential in APB during 2-10 N thumb
      abduction (P < 0.0001) versus rest, but not with lower target forces (0.5, 1 N).
      Conditioning TMS was less effective for FDI and ADM only during 10 N thumb
      abduction. We conclude that differential modulation of ICI in M1 during selective
      muscle activation is a function of target isometric force level. At low forces
      (<5% MVC), ICI is not modulated for the corticospinal neurons controlling the
      active or inactive muscles. There is a progressive reduction of ICI effects on
      corticospinal neurons at higher forces, which is largely restricted to
      corticospinal neurons controlling the muscle targeted for activation over the
      range of forces tested (up to approximately 25% MVC). The pattern of ICI
      modulation with selective voluntary muscle contraction was similar in left and
      right hemispheres during this relatively simple static task. If hemispheric
      differences in operation of M1 ICI circuits contribute to hand preference, a more
      challenging finger movement protocol may be needed to demonstrate this asymmetry.

PMID- 16947063
TI  - Fixation offset facilitates saccades and manual reaching for single but not
      multiple target displays.
AB  - Turning off a fixation point, typically for 200 ms, before the onset of a
      peripheral target substantially reduces saccadic reaction times. This
      facilitatory effect generated by an inserted temporal gap between fixation offset
      and the target appearance is called the "gap" effect [J Opt Soc Am 57:1030-1033,
      1967]. We show that the gap reduces the initial latency of both saccades and
      manual pointing in single and multiple target displays. Yet, in multiple target
      displays, the gap increased the movement duration because eye or hand movements
      were frequently misdirected toward distractors so that the trajectory had to be
      corrected. Thus, in spite of the shortened latency, the total time for trial
      completion was not shortened in multiple target displays, whereas it was reduced
      in single target displays. This selective gap effect for a single target was not
      restricted to goal-directed motor tasks because perceptual discrimination tasks,
      where no motor response is required, also demonstrated the gap effect only for
      single target displays. Our results suggest that the gap may facilitate
      attentional disengagement, but it does not help target selection in motor and
      perceptual discrimination tasks, where the allocation of attention to the target
      is required.

PMID- 16947064
TI  - Corticomotor facilitation associated with observation, imagery and imitation of
      hand actions: a comparative study in young and old adults.
AB  - In the present report, we extent our previous findings (Clark et al. in
      Neuropsychologia 42:105-122, 2004) on corticomotor facilitation associated with
      covert (observation and imagery) and overt execution (action imitation) of hand
      actions to better delineate the selectivity of the effect in the context of an
      object-oriented action. A second aim was to examine whether the pattern of
      facilitation would be affected by age. Corticomotor facilitation was determined
      in two groups of participants (young n = 21, 24 +/- 2 years; old n = 19, 62 +/- 6
      years) by monitoring changes in the amplitude and latency of motor evoked
      potentials (MEPs) elicited in hand muscles by transcranial magnetic stimulation.
      MEP responses were measured from both the first dorsal interosseous (FDI, task
      selective muscle) and the abductor digiti minimi (ADM) of the right hand while
      participants attended to four different video presentations. Each of four videos
      provided specific instructions for participants to either: (1) close their eyes
      and relax (REST), (2) observe the action attentively (OBS), (3) close their eyes
      and mentally simulate the action (IMAG), or (4) imitate the action (IMIT). The
      action depicted in the videos represented a male subject cutting a piece of
      material with scissors. In the young group, the pattern of results revealed
      selective facilitation in the FDI in conditions involving either covert (OBS and
      IMAG) or overt action execution (IMIT). In the ADM, only overt execution with
      action imitation was associated with significant MEP facilitation. In the old
      group, a similar pattern of results was observed, although the modulation was
      less selective than that seen in the young group. In fact, older individuals
      often exhibited concomitant facilitation in both the FDI and ADM during either
      covert (OBS and IMAG conditions) or overt action execution (IMIT condition).
      Taken together, these results further corroborate the notion that the
      corticomotor system is selectively active when actions are covertly executed
      through internal simulation triggered by observation or by motor imagery, as
      proposed by Jeannerod (Neuroimage 14:S103-S109, 2001). With aging, the ability to
      produce corticomotor facilitation in association with covert action execution
      appears to be largely preserved, although there seems to be a loss in
      selectivity. This lack of selectivity may, in turn, reflect age-related
      alterations in the function of the corticospinal system, which may impair the
      ability to individuate finger movements either in the covert or overt stage of
      action execution.

PMID- 16947066
TI  - Sperm binding glycoprotein is differentially present surrounding the lumen of
      isthmus and ampulla of the pig's oviduct.
AB  - In several mammals a sperm reservoir is formed at the isthmus of the Fallopian
      tube, providing viable, potentially fertile sperm for an extensive period. In pig
      (Sus scrofa) the spermadhesin AQN-1 seems to be involved in the establishment of
      the sperm reservoir. The pig oviductal protein, sperm binding glycoprotein (SBG),
      binds to sperm and exposes carbohydrate groups that can be recognized by AQN-1.
      In this study we obtain anti-SBG polyclonal antibodies and use them to localize
      SBG in the oviduct. Immunohistochemical analysis shows that SBG is present at the
      apical surface of isthmic and ampullar epithelial cells. The presence of SBG is
      limited to the upper two-thirds of the crypts of the isthmus and to cells located
      near the oviductal lumen in the ampulla. The ratio of the amount of SBG detected
      by western blot is 1:3 (ampulla:isthmus). Sperm entering the Fallopian tube
      probably contact the epithelial cells at the lumen before they reach the cells at
      the bottom of the folds. In vitro sperm can bind to isthmus and, at less extent,
      to ampulla. Thus, the localization and the relative amount of SBG in the isthmus
      and ampulla of pig's oviduct are compatible with its possible function in sperm
      binding to oviductal epithelial cells.

PMID- 16947065
TI  - [High-grade osteosarcoma of the maxillary sinus. A case report].
AB  - BACKGROUND: Osteosarcoma of the jaw (JOS) constituting 5% to 13% of all
      osteosarcoma is a locally aggressive malignant mesenchymal tumor with high
      tendency to local recurrence and the ability to produce tumor osteoid. Compared
      to osteosarcoma of the remaining skeleton (SOS) JOS metastasizes relatively
      rarely and relatively late. It differs significantly from SOS in its biological
      behaviour. CASE REPORT: The presented case deals with a 60-year-old male patient
      suffering from a newly occurred polypous mucosal tumor of the right-sided
      maxillary alveolar ridge bioptically diagnosed as a granulation tissue polyp
      first. After transmaxillary resection of the tumor and consultation of a bone
      tumor reference center the final diagnosis of a high-grade chondroblastic
      osteosarcoma could be made. The recommended radical resection of the tumor was
      declined by the patient because of the expected cosmetic consequences. After
      surgical reduction of the rapidly growing sarcoma chemotherapy according to the
      COOS/EURO-B.O.S.S. protocol was initiated at a stage when computed tomography
      showed diffuse metastatic disease to the lungs. Chemotherapy could delay the
      progress of the disease only temporarily. The patient died from respiratory
      insufficiency. CONCLUSION: In JOS radical surgical resection is the therapy of
      first choice. For substantiation of the diagnosis and central registration of the
      cases a bone tumor reference center should be contacted.

PMID- 16947067
TI  - Drug-related problems in general practice: results from a development project in
      Denmark.
AB  - OBJECTIVE: The objective of the study is identify and document drug-related
      problems and other possible quality problems in primary care through a pharmacist
      run medication review and screening service. GPs' acceptance and implementation
      rates of the pharmacist's recommendations are evaluated. METHOD: A community
      pharmacist worked 20 h per week for 18 months in a GP practice with three GPs.
      RESULTS: The pharmacist completed 40 reviews and identified 103 drug-related
      problems. GPs had a high rate of acceptance of the pharmacist's suggested
      interventions (83%), and 77% of the recommendations had been implemented. 765
      (12.5%) possible quality problems were identified after screening 6094 medical
      records. The physicians accepted 86% of the recommendations to initiate low
      dosage ASA and treatment was implemented for 63% of the patients. 76% of the
      recommendations to initiate Statin treatment were agreed on and 56% were
      implemented. CONCLUSIONS: The pharmacist was able to identify drug-related
      problems and other possible quality problems with regard to quality assurance of
      individual patient's drug treatment. The GPs accepted and implemented the
      pharmacist's recommendations. It was feasible to implement the services and to
      establish well-functioning co-operation between the pharmacist and the GPs.

PMID- 16947069
TI  - Venous spread of renal cell carcinoma: MDCT.
AB  - BACKGROUND: The purpose of our study was to present multidetector computed
      tomography (MDCT) findings in venous spread of renal cell carcinoma (RCC), to
      determine the superior extent of tumor thrombus and to compare MDCT findings with
      surgical report. METHODS: The prospective MDCT study was performed on 31 patients
      diagnosed with RCC with venous spread (19 males and 12 females; age range 39-80
      years; mean age 62.6 years). CT scans were obtained by MDCT scanner, in triphasic
      scanning protocol. All postprocessing techniques were performed by two
      independent radiologists, and the findings were reported in their consensus. MDCT
      diagnosis was compared with surgical and pathohistological findings. RESULTS:
      Tumor thrombus extension into renal vein only (T3b stage) was found in 13/31
      (42%) patients. Involvement of infradiaphragmatic level of inferior vena cava
      (IVC) (T3c stage) was found in 14/31 (45%) patients and supradiaphragmatic level
      of IVC (T4b stage) in 4/31 (13%) patients. In 27/31 (87%) patients surgery was
      performed, while 4/31 (13%) could not undergo surgery. In comparison with
      surgical report, in 25/27 (93%) operated patients the upper extent of the tumor
      thrombus was correctly diagnosed by MDCT, and 2/27 (7%) patients were falsely
      diagnosed. CONCLUSION: MDCT represents a fast, relatively inexpensive, and
      reliable diagnostic method for evaluating the venous spread of RCC as well as the
      level of its upper extent. Triphasic MDCT is often the only diagnostic method
      necessary for planning the surgical procedure. Surgery should be performed as
      soon as possible for MDCT findings to be valid.

PMID- 16947070
TI  - Pericecal hernia of the inferior ileocecal recess: CT findings.
AB  - Internal abdominal herniations are rare. A 34-year-old healthy man was seen in
      the emergency room because of severe lower abdominal pain and episodic vomiting.
      Pericecal internal herniation of the inferior ileocecal recess was suspected by
      abdominal CT study and confirmed by exploratory laparotomy. Finally, the
      herniated ileal loops were reduced, and the redundant peritoneum was resected. In
      the present case, CT demonstrates the precise anatomic diagnosis and shows acute
      complications that should be recommended preoperatively. Urgent surgical
      intervention is necessary to prevent strangulation, which is responsible for high
      mortality. Early diagnosis and treatment had a good outcome.

PMID- 16947071
TI  - Sonographic subcutaneous and visceral fat indices represent the distribution of
      body fat volume.
AB  - BACKGROUND: A reliable method for direct measurement of both subcutaneous and
      visceral fat volume is the measurement of fat tissue area from tomographic
      pictures by CT or by MR imaging. However, these are not widely usable because of
      high cost and/or exposure to radiation. METHODS: We compared sonographic
      subcutaneous and visceral fat indices with fat distribution by serial-slice MR
      imaging in 17 subjects. Sonographic subcutaneous or visceral fat index is
      standardized thickness of subcutaneous fat tissue or the intra-abdominal depth at
      the level of umbilicus by height. RESULTS: Sonographic visceral fat index and
      intra-abdominal depth were significantly correlated with visceral fat volume by
      serial-slice MR imaging (r = 0.746, r = 0.726, respectively). Similarly,
      sonographic subcutaneous fat index and subcutaneous fat thickness were
      significantly correlated with subcutaneous fat volume by serial-slice MR imaging
      (r = 0.825, r = 0.816, respectively). The ratio of sonographic visceral fat index
      and sonographic subcutaneous fat index was closely correlated with the ratio of
      the visceral fat volume and the subcutaneous fat volume by single-slice MR
      imaging, which proves to be related to cardiovascular disease risk (r = 0.722).
      CONCLUSION: Sonographic subcutaneous or visceral fat index could be an easily
      measured and inexpensive indicator for the assessment of fat distribution instead
      of CT or MR imaging.

PMID- 16947072
TI  - Colitis cystica profunda: MRI appearance.
AB  - Colitis cystica profunda (CCP) is an uncommon benign condition characterized by
      mucin-filled cysts located in the submucosa, frequently associated with the
      solitary ulcer and rectal prolapse syndromes. The diagnosis of this entity is
      important as it can mimic rectal cancer and therefore may result in unnecessary
      surgical resection. Endoscopic examination and barium enema findings are
      suggestive but not specific, neither are superficial biopsy findings. Transrectal
      ultrasound is helpful in the diagnosis by imaging the layers of the rectal wall.
      The authors report a 16-year-old male with a rectal lesion mimicking malignant
      mass on endoscopic examination. The lesion was defined as CCP, based on MR
      imaging findings which disclosed multiple noninfiltrating submucosal cysts,
      confirmed by histopathological examination. To our knowledge, this is the first
      case of CCP in the radiology literature describing MRI findings.

PMID- 16947073
TI  - Adnexal ring of ectopic pregnancy detected by contrast-enhanced CT.
AB  - We present a case of a 37-year-old woman who presented with acute right lower
      quadrant abdominal pain. Work up with contrast enhanced CT to rule out
      appendicitis revealed dramatic ring enhancing cystic structure in the right
      adnexa corresponding to tubal ring sign of ectopic pregnancy seen on subsequent
      pelvic ultrasound. Right tubal ectopic pregnancy was confirmed at surgery.

PMID- 16947074
TI  - Fournier's gangrene: a radiologic emergency.
AB  - Fournier's gangrene (FG) is a life-threatening, necrotizing infection involving
      the soft tissues of the scrotal area. Because of potential severe complications,
      it is important to diagnose the disease as early as possible. We present the CT
      findings of FG in a young male that came to the Emergency Department for genital
      pain and tenderness.

PMID- 16947075
TI  - Reconstituted micelle formation using reduced, carboxymethylated bovine kappa
      casein and human beta-casein.
AB  - In milk, kappa-casein, a mixture of disulfide-bonded polymers, stabilizes and
      regulates the size of the unique colloidal complex of protein, Ca2+ and inorganic
      phosphate (Pi) termed the casein (CN) micelle. However, reduced,
      carboxymethylated bovine kappa-CN (RCM-kappa) forms fibrils at 37 degrees C and
      its micelle-forming ability is in question. Here, the doubly- and quadruply
      phosphorylated human beta-CN forms and 1:1 (wt:wt) mixtures were combined with
      RCM-kappa at different beta/kappa weight ratios. Turbidity (OD(400 nm)) and a
      lack of precipitation up to 37 degrees C were used as an index of micelle
      formation. Studies were with 0, 5 and 10 mM Ca2+ and 4 and 8 mM Pi. The RCM-kappa
      does form concentration-dependent micelles. Also, beta-CN phosphorylation level
      influences micelle formation. Complexes were low-temperature reversible and RCM
      kappa fibrils were seen. There appears to be equilibrium between fibrillar and
      soluble forms since the solution still stabilized after fibril removal. The RCM
      kappa stabilized better than native bovine kappa-CN.

PMID- 16947076
TI  - Amino acid sequence and activity of green turtle (Chelonia mydas) lysozyme.
AB  - Green turtle lysozyme purified from egg white was sequenced and analyzed its
      activity. Lysozyme was reduced and pyridylethylated or carboxymethylated to
      digest with trypsin, chymotrypsin and V8 protease. The peptides yielded were
      purified by RP-HPLC and sequenced. Every trypsin peptide was overlapped by
      chymotrypsin peptides and V8 protease peptides. This lysozyme is composed of 130
      amino acids including an insertion of a Gly residue between 47 and 48 residues
      when compared with chicken lysozyme. The amino acid substitutions were found at
      subsites E and F. Namely Phe34, Arg45, Thr47, and Arg114 were replaced by Tyr,
      Tyr, Pro, and Asn, respectively. The time course using N-acetylglucosamine
      pentamer as a substrate showed a reduction of the rate constant of glycosidic
      cleavage and transglycosylation and increase of binding free energy for subsite
      E, which proved the contribution of amino acids mentioned above for substrate
      binding at subsites E and F.

PMID- 16947077
TI  - Proteome comparison following self- and across-pollination in self-incompatible
      apricot (Prunus armeniaca L.).
AB  - The study compared the protein differences between self- and across-pollinated
      self-incompatible (SI) apricots by two-dimensional gel electrophoresis and liquid
      chromatography-electrospray ion trap tandem mass spectrometry, the results showed
      that nine protein spots were expressed in self-pollinated pistil and only one was
      expressed in cross-pollinated pistils. Sixteen and three protein spots were up-
      and down-regulated in cross-pollinated pistils, respectively, compared with self
      pollinated pistils. Seven protein spots were identified unambiguously by SEQUEST
      in NCBI protein database: Actin-12, enolase, MYB transcription-factor-like
      protein, heat-shock protein 70 were upregulated in cross-pollinated pistils
      compared with self-pollinated pistils; and actin-7, actin-8 and fructose
      bisphosphate aldolase-like protein were detected only in self-pollinated pistils.

PMID- 16947078
TI  - The complete amino acid sequence of green turtle (Chelonia mydas) egg white
      ribonuclease.
AB  - Egg white ribonuclease was first found in green turtle eggs. This enzyme has been
      purified by CM-toyopearl cation exchange. Two isoforms (GTRNase-1 and GTRNase-2)
      were further separated by RP-HPLC, with the same M.W. (13 kDa) and activity.
      These isoforms carried one amino acid exchange of Ser and Leu at the position 37.
      The N-terminal sequence, ETRYEKF, was determined for the transblotted protein.
      Internal sequences were analyzed by protein sequencer and ESI-Q-TOF mass
      spectrometry for tryptic peptides (Ts). The overlapping sequences were obtained
      from chymotryptic peptides, CNBr fragments and ISD-MS/MS analysis. The C-terminal
      Ile was identified by CPase-Y. The established sequence composed of 119 residues
      with the molecular mass of 12,942.1 Da for GTRNase-1 and 12,967.8 Da for GTRNase
      2. The comparison of sequence with known pancreatic RNases, 27 positions
      including catalytic residues at the position 11 and 114 were conserved. Also
      basic residues contributed to phosphate binding residues were conserved with the
      exception of Lys 66. One insertion at the position 14, and 3 deletions at the
      position-1, between position 64-65, and 110 and 111 were found. Two Cys residues
      at position 65 and 72 that form a disulfide bond in mammalian RNase were deleted
      and exchanged. All these difference in the sequence were similar to reptile
      pancreatic RNase.

PMID- 16947079
TI  - Expression and purification of human PAG, a transmembrane adapter protein using
      an insect cell expression system and its structure basis.
AB  - In this study, we report the purification and structure basis of human
      phosphoprotein associated with glycosphingolipid-enriched microdomains (PAG), a C
      SRC tyrosine kinase (CSK)-binding protein. Human PAG was produced using an insect
      cell expression system. The PAG was purified by metal affinity, ion exchange, and
      gel filtration chromatographies. The final purity of gel-purified PAG was
      evaluated by SDS-PAGE and mass spectrometry. Recombinant human PAG migrates to 60
      kDa on SDS-PAGE gel, while native PAG is a 46 kDa transmembrane adapter protein
      in lipid rafts. Recombinant human PAG has a difference of 2590.7 Da with a
      calculated mass (47803.41 Da) and an observed mass (50394.1 Da) by mass
      spectrometry. Consequently, although human PAG sequence shares well-known sites
      for modifications such as myristoylation, palmitoylation, and tyrosine
      phosphorylation sites, perhaps the difference suggests the existence of unknown
      modification sites. We show the high PAG-binding ability with CSK in vitro as
      well as the human PAG structure characterized by 11 alpha-helix structures
      including a 3 kDa transmembrane domain.

PMID- 16947080
TI  - Interaction between Abeta peptide and alpha synuclein: molecular mechanisms in
      overlapping pathology of Alzheimer's and Parkinson's in dementia with Lewy body
      disease.
AB  - Amyloidogenic proteins (Abeta peptide) in Alzheimer's disease (AD) and alpha
      synuclein (alpha-Syn) in Parkinson's disease (PD) are typically soluble monomeric
      precursors, which undergo remarkable conformational changes and culminate in the
      form of aggregates in diseased condition. Overlap of clinical and
      neuropathological features of both AD and PD are observed in dementia with Lewy
      body (DLB) disease, the second most common form of dementia after AD. The
      identification of a 35-amino acid fragment of alpha-Syn in the amyloid plaques in
      DLB brain have raised the possibility that Abeta and alpha-Syn interact with each
      other. In this report, the molecular interaction of alpha-Syn with Abeta40 and/or
      Abeta42 are investigated using multidimensional NMR spectroscopy. NMR data in the
      membrane mimic environment indicate specific sites of interaction between
      membrane-bound alpha-Syn with Abeta peptide and vice versa. These Abeta-alpha-Syn
      interactions are demonstrated by reduced amide peak intensity or change in
      chemical shift of amide proton of the interacting proteins. Based on NMR results,
      the plausible molecular mechanism of overlapping pathocascade of AD and PD in DLB
      due to interactions between alpha-Syn and Abeta is described. To the best of our
      knowledge, it is the first report using multidimensional NMR spectroscopy that
      elucidates molecular interactions between Abeta and alpha-Syn which may lead to
      onset of DLB.

PMID- 16947081
TI  - Investigation of the multi-step dehydration reaction of theophylline monohydrate
      using 2-dimensional powder X-ray diffractometry.
AB  - PURPOSE: (i) To study the dehydration kinetics of theophylline monohydrate using
      2-dimensional (2D) powder X-ray diffractometry (XRD), and (ii) to investigate the
      effect of polyvinylpyrrolidone (PVP) on the dehydration pathway and kinetics.
      METHODS: Theophylline monohydrate (C(7)H(8)N(4)O(2).H(2)O; M) was recrystallized
      from aqueous PVP solutions of different concentrations. Dehydration kinetics was
      studied isothermally, at several temperatures, from 35 to 130 degrees C. The
      experimental set-up comprised of a high intensity X-ray source (synchrotron
      radiation or 8 kW rotating anode), a heating chamber, and a 2D area detector.
      Diffraction patterns were collected continuously, with a time resolution ranging
      from 40 ms to 30 s, over the angular range of 3 to 27 degrees 2theta. RESULTS:
      Dehydration of M resulted in either the stable (C(7)H(8)N(4)O(2); A), or the
      metastable anhydrate (A*), with the latter having a tendency to transform to A.
      The XRD technique allowed simultaneous quantification of M, A* and A during the
      dehydration reaction. The rate constants for individual reaction steps (M-->A*; M
      ->A and A*-->A) were determined by fitting the data to solid-state reaction
      models. In presence of PVP, there was a decrease in the magnitude of the rate
      constant associated with the M-->A transition, resulting in an increased build-up
      of A* in the product. The inhibitory effect of PVP on M-->A transition was more
      pronounced at lower dehydration temperatures, and was proportional to the
      concentration of PVP. CONCLUSIONS: Two dimensional powder X-ray diffractometry,
      using a high intensity source, is a powerful technique to study kinetics of rapid
      solid-state reactions. The inhibitory effect of excipients can have profound
      effect on phases formed during pharmaceutical processing.

PMID- 16947082
TI  - The role of the epidermal growth factor receptor in breast cancer.
AB  - Recent trials of drug therapy targeting the erbB receptor HER2 have met with
      success in breast cancer. The epidermal growth factor receptor or EGFR is a
      closely related receptor from this same family that is involved in cellular
      signal transduction and tumor cell growth and survival. Emerging evidence
      indicates that EGFR is implicated in the development of hormone-resistant breast
      cancer, and that its activity is intertwined with estrogen receptor. Here, the
      role of EGFR in breast cancer is reviewed, and data from selected clinical trials
      of signal transduction inhibition of this cellular target are summarized.

PMID- 16947083
TI  - The ErbB2 signaling network as a target for breast cancer therapy.
AB  - Overexpression of the ErbB2/Her2 receptor tyrosine kinase in breast cancers is
      associated with the most aggressive tumors. Experimental studies have revealed
      that ErbB2 shows many features of a therapeutic target: ErbB2 is able to confer
      many of the characteristics of a cancerous cell, including uncontrolled
      proliferation, resistance to apoptosis and increased motility; ErbB2
      overexpression is specific to tumor cells; as a cell surface-associated protein,
      it is easily accessible to drugs and as a kinase it is amenable to targeted
      inhibition by small molecules. Recent clinical results demonstrate the efficacy
      of ErbB2-targeting therapy and promise an expanding use of ErbB2-targeting drugs
      for breast cancer treatment. However, as only a fraction of patients responds
      successfully to therapy and risks of recurrence are still high, further
      investigation is required for an improved understanding of the complex network of
      signaling pathways underlying ErbB2-driven cancer progression.

PMID- 16947084
TI  - Inhibitors of insulin-like growth factor signaling: a therapeutic approach for
      breast cancer.
AB  - The peptide growth factors IGF-I and IGF-II not only play a role in the
      development of the mammary gland but are also implicated in breast cancer.
      Several reagents disrupting IGF signaling have been developed and clinical trials
      validating IGF signaling as a target in cancer therapy are underway. This review
      highlights the approaches to inhibiting IGF signaling in breast cancer.

PMID- 16947085
TI  - Notch signaling in breast cancer and tumor angiogenesis: cross-talk and
      therapeutic potentials.
AB  - Notch signaling is an evolutionarily conserved pathway that regulates numerous
      physiological processes. Disruption of Notch has been implicated in multiple
      tumor types. Evidence from in vitro experiments, mouse models and human tumor
      samples indicates that Notch plays a predominantly oncogenic role in breast
      cancer and interacts with other pathways involved in tumorigenesis. In addition,
      Notch signaling is required for physiological angiogenesis and may promote tumor
      angiogenesis. A variety of strategies for blocking Notch signaling, in particular
      gamma-secretase inhibition, are discussed as potential therapies for breast
      cancer and tumor angiogenesis.

PMID- 16947087
TI  - Surgical treatment of chronic thromboembolic pulmonary hypertension.
AB  - Chronic thromboembolic pulmonary hypertension is a commonly overlooked cause of
      physical incapacity and dyspnoea, with a higher incidence than is generally
      appreciated and a poor prognosis. The diagnosis can be suspected based on
      echocardiographic examinations and ventilation perfusion scanning of the lung.
      Pulmonary angiography still remains the gold standard for the diagnosis of
      thromboembolic pulmonary hypertension and the assessment of operability.
      Pulmonary endarterectomy is a complex surgical procedure, which provides
      permanent relief of thromboembolic pulmonary hypertension and cure for most of
      the patients. The operation resembles a true endarterectomy of the pulmonary
      artery branches using extracorporeal circulation and periods of hypothermic
      circulatory arrest. In experienced centres, the operative risk has been decreased
      to an acceptable level. Following successful surgery, long-term survival and
      quality of life are excellent. Earlier referral to surgery might avoid the
      occurrence of a secondary vasculopathy in the unaffected areas of the pulmonary
      vascular tree, and therefore further improve early and late results. A
      multidisciplinary approach and surgical experience are the prerequisites for
      success of this demanding procedure.

PMID- 16947088
TI  - In utero haematopoietic stem cell transplantation. Experiences in mice, sheep and
      humans.
AB  - Early prenatal diagnosis and in utero therapy of certain fetal diseases have the
      potential to reduce fetal morbidity and mortality. The intrauterine
      transplantation of stem cells provides in some instances a therapeutic option
      before definitive organ failure occurs. Clinical experiences show that certain
      diseases, such as immune deficiencies or inborn errors of metabolism, can be
      successfully treated using stem cells derived from bone marrow. However, a
      remaining problem is the low level of engraftment that can be achieved. Efforts
      are made in animal models to optimise the graft and study the recipient's
      microenvironment to increase long-term engraftment levels. Our experiments in
      mice show similar early homing of allogeneic and xenogeneic stem cells and
      reasonable early engraftment of allogeneic murine fetal liver cells (17.1% donor
      cells in peripheral blood 4 weeks after transplantation), whereas xenogeneic HSC
      are rapidly diminished due to missing self-renewal and low differentiation
      capacities in the host's microenvironment. Allogeneic murine fetal liver cells
      have very good longterm engraftment (49.9% donor cells in peripheral blood 16
      weeks after transplantation). Compared to the rodents, the sheep model has the
      advantage of body size and gestation comparable to the human fetus. Here,
      ultrasound-guided injection techniques significantly decreased fetal loss rates.
      In contrast to the murine in utero model, the repopulation capacities of
      allogeneic ovine fetal liver cells are lower (0.112% donor cells in peripheral
      blood 3 weeks after transplantation). The effect of MHC on engraftment levels
      seems to be marginal, since no differences could be observed between autologous
      and allogeneic transplantation (0.117% donor cells vs 0.112% donor cells in
      peripheral blood 1 to 2 weeks after transplantation). Further research is needed
      to study optimal timing and graft composition as well as immunological aspects of
      in utero transplantation.

PMID- 16947086
TI  - The biological functions of the versatile transcription factors STAT3 and STAT5
      and new strategies for their targeted inhibition.
AB  - Signal transducers and activators of transcription (STATs) comprise a unique
      family of transcription factors, which transmit the interactions of cytokines,
      hormones and growth factors with their cell surface receptors into
      transcriptional programs. The mechanism of STAT activation has been well
      established and comprises tyrosine phosphorylation, dimerization, nuclear
      translocation, binding to specific DNA response elements, recruitment of co
      activators or co-repressors and transcriptional induction or repression of target
      genes. Gene deletion, microarrays, proteomics and chromatin immunoprecipitation
      experiments have revealed target genes with a broad range of functions regulated
      by STAT3 and STAT5. In the mammary gland, STAT5-induced genes contribute mainly
      to the prolactin dependent lobulo-alveolar development, whereas STAT3 induced
      genes control apoptosis during involution. Crucial effects have also been
      observed in other tissues. The germ line deletion of STAT3 or STAT5 causes early
      embryonal or perinatal lethality in mice. STAT5 is also required for
      proliferation of T- and B-cells and hematopoietic stem cell self-renewal.
      Deregulated STAT activity is often found associated with tumorigenesis and
      activated STATs seem to be limiting components in tumor cells. This review
      summarizes the functions of STAT3 and STAT5 in different cell types and the
      strategies that are used to counteract their action in tumor cells.

PMID- 16947089
TI  - Clinical experiences with bisphopsphonate induced osteochemonecrosis of the jaws.
AB  - QUESTION: Bisphosphonates are frequently used drugs in the adjuvant therapy of
      bone metastases and tumour-induced hypercalcaemia, but also for osteoporosis or
      Pagets disease. Several publications within the last three years considered
      osteonecrosis of the jaws to be connected with bisphosphonate therapy. Until
      today possible treatment strategies contain antibiotics, hyperbaric therapy and
      operative treatment. The tendency of healing however seems to be extremely poor.
      All clinicians should be aware of this new kind of side effect of bisphosphonate
      therapy. METHODS: 14 patients with this new kind of osteonecrosis were admitted
      to the department of Cranio-Maxillofacial Surgery of the University Hospital of
      Zurich. 8 men and 6 women all received bisphosphonates for cancer therapy. A
      complete analysis of patients' data was performed. RESULTS: Of 14 patients in 7
      the underlying disease disease was multiple myeloma. In one patient it was
      prostate cancer and in all female patients it was breast cancer. All of them had
      prior dental treatment and showed inflammatory signs and bacterial colonisation
      with localisation in the upper or lower jaw or in both. CONCLUSION: The
      infectious part of the bisphosphonate-induced osteonecrosis (ONJ) is considered
      to be more important than thought before. We presume that antimicrobial treatment
      is of utmost importance in the treatment of this kind of osteonecrosis. Patients
      with current or previous bisphosphonate therapy should be treated
      multidisciplinary to assure ideal prevention and treatment.

PMID- 16947090
TI  - Antioxidant effects of hormone replacement therapy in postmenopausal women.
AB  - QUESTIONS UNDER STUDY: Postmenopausal women are more likely to develop coronary
      artery disease than premenopausal women of the same age. Postmenopausal oral
      oestrogen therapy is associated with increased levels of high-density lipoprotein
      (HDL) cholesterol and decreased levels of lowdensity lipoprotein (LDL)
      cholesterol. In this study we investigated the direct contribution of hormone
      replacement therapy on total antioxidant capacity rather than its effects on the
      serum lipid profile. METHODS: At the time of enrolment and after the drug
      delivery plasma total cholesterol, triglycerides (TG), HDL, LDL, uric acid, total
      bilirubin, albumin, oestradiol levels and total antioxidant capacity of plasma
      were assessed. RESULTS: Levels of plasma TG and total antioxidant capacity were
      significantly increased in the study group. CONCLUSIONS: Our results suggest that
      oestrogen has an antioxidant effect following 3 months of hormone replacement
      therapy. Progesterone in combination with oestrogen does not have this effect.
      Also plasma TG levels increased in those patients receiving HRT after 3 months.

PMID- 16947091
TI  - Swiss patients with variegate porphyria have unique mutations.
AB  - BACKGROUND: Variegate porphyria (VP), also known as South African porphyria, is a
      low-penetrance, autosomal dominant disorder as the result of a partial deficiency
      of protoporphyrinogen oxidase (PPOX). Clinically, VP is characterised by
      photosensitivity and neurovisceral attacks whereby the two symptoms can appear
      separately or together in patients. VP is little known in Switzerland. In this
      study, we report a clinical, biochemical and mutational study of eight Swiss VP
      patients and their families. RESULTS: Six of the eight index patients presented
      with only skin symptoms, and one with only neurological symptoms. Another patient
      had both skin and neurological symptoms. Faecal porphyrin excretion was elevated
      in all patients thus enabling diagnosis. Four different mutations including three
      novel mutations (G11D, 1041-1042 ins T and 1262-1263 ins 22bp) were identified in
      this cohort. Mutation 1082-1083 ins C, which had been reported in the French VP
      population, was shared by five apparently unrelated patients of this study.
      CONCLUSION: The novel PPOX gene mutations are apparently unique to the Swiss
      population. Both clinical and biochemical presentations varied considerably even
      among those patients who carried an identical mutation, which does not favour the
      existence of a genotype-phenotype correlation in VP.

PMID- 16947092
TI  - [Neurocognitive and psychosocial development in SGA and the indication for growth
      hormone therapy].
AB  - After recent approval of treatment indication for growth hormone therapy (GHT) in
      SGA (small for gestational age) treatment expectations do not only refer to
      improvement of growth parameters but also to enhancement of suspected impairments
      of neurocognitive, behavioural and educational development. Clinical prognosis,
      however, is difficult which specific developmental risks are to be expected in
      the individual case and if their course may response to GHT. The paper reviews
      recent findings of clinical and population-based studies on neurocognitive and
      psychosocial outcome in SGA and delineates an integrative framework on the
      emergence and course of potential developmental risk comprising three major
      causes: Conclusions are drawn for the clinical differentiation of specific
      adaptation difficulties towards short stature versus global, short stature
      independent behavioral disorders. Psychosocial outcome parameters can be expected
      to respond best to endocrinological growth stimulation in conditions with a high
      specific short stature related maladjustment; in turn, the relevance of child
      psychology interventions increases in conditions with global disturbance and
      short stature independent origin.

PMID- 16947093
TI  - [Asymptomatic carnitine depletion on ketogenic diet in patients with
      pharmacoresistant epilepsies].
AB  - BACKGROUND: The ketogenic diet (KD) is a nutritional therapy for the treatment of
      epilepsies and certain metabolic disorders like the glucose-transporter
      deficiency or the pyruvate-dehydrogenase-deficiency. The basis of the ketogenic
      diet is the change of energy metabolism to utilisation of fatty acids and their
      metabolites, ketonic bodies. Carnitines, which play an important role in
      transport and elimination of fatty acids, are essential for effective
      ketogenesis. Carnitine deficiency is described on ketogenic diet. The aim of this
      study is to evaluate when to expect a carnitine-deficiency during KD. PATIENTS:
      The carnitine levels of 19 patients aged 1.4 to 8.5 years (median 4.0 years), who
      were treated with ketogenic diet because of pharmacoresistent epilepsy, were
      evaluated retrospectively. RESULTS: Carnitine deficiency during KD was detected
      in 26 % of the patients and in 57 % of the patients without carnitine
      substitution. Decreased carnitine level occurred also with carnitine substitution
      independent from additional valproat therapy. The time of appearance of carnitine
      deficiency on KD was between 3 days and 248 weeks (median 32 weeks). CONCLUSION:
      Regular controls of carnitine levels should be performed during the treatment
      with ketogenic diet, both at the beginning and during longterm-therapy.

PMID- 16947094
TI  - [Indications for intermittent diazepam prophylaxis in febrile seizures].
AB  - BACKGROUND: In a prospective controlled study we evaluated the efficacy of
      intermittent diazepam prophylaxis in the recurrence rate of febrile seizures
      (FS). PATIENTS: A total of 139 children aged between 6 and 36 months, who had a
      first FS, were enrolled in the study and were randomly allocated to two groups:
      group (A) that received diazepam prophylaxis and group (B) without prophylaxis.
      METHODS: All children were followed up for at least 3 years after their first FS.
      The prophylaxis group (n = 68) received rectal diazepam the first two days of a
      febrile illness, whenever the temperature was > 38 degrees C (0.33 mg/kg every 8
      h on the first day, and 0.33 mg/kg every 12 h on the second day of fever, max.
      dosage 7.5 mg). The no-prophylaxis group (n = 71) did not receive any prophylaxis
      at all. Each group was stratified to low, intermediate and high risk subgroups
      according to the following clinical data: age at the first febrile seizure </= 15
      months, positive family history of febrile seizure or epilepsy in first degree
      relatives, complex first febrile seizure and frequent febrile illness. RESULTS:
      The 3-year recurrence rates in the no-prophylaxis group were 83 % in high- risk,
      55 % in intermediate-risk and 46 % in low-risk patients. In the prophylaxis group
      we established a reduction of febrile seizure recurrence at 38 %, 35 % and 33 %
      in the three risk subgroups respectively. CONCLUSION: The intermittent
      prophylaxis with rectal diazepam during febrile episodes lead to a reduction of
      febrile seizure recurrence, especially in high-risk patients. The results of our
      study set the indication for the use of intermittent diazepam prophylaxis in this
      subgroup.

PMID- 16947095
TI  - [The use of implantable cardioverter-defibrillators (ICD) in children and
      adolescents].
AB  - BACKGROUND: The compelling safety and efficacy data in numerous large, blinded
      trials on adult patients, and the progress in device- and leadtechnology have led
      to increasing use of implantable cardioverter defibrillators in pediatric
      patients. The purpose of our study was to assess the efficacy and safety of ICD
      in the pediatric age group of a tertiary referral centre. PATIENTS AND METHODS:
      Between March 1998 and October 2003 12 patients underwent ICD-implantation. The
      mean age at implantation was 14,8 years with a range between 10-17 years. The
      underlying cardiac disorders included long QT-syndrome in 4 patients, ventricular
      fibrillation in 3 patients, dilated cardiomyopathy in 4 patients, and congenital
      heart disease in 1 patient (pulmonary atresia with ventricular septal defect
      after Rastelli repair). All patients received a transvenous ICD-system (VVI-ICD
      in 4 patients, DDD-ICD in 8 patients). RESULTS: The mean follow up was 35 months
      (6-68 months). During this period there were no severe complications nor
      mortality. We haven't seen infections, thromboembolic complications or lead
      perforations. 2 patients (17 %) received appropriate DC-shocks, 1 patient (8 %)
      received an inappropriate DC-shock. 10 patients (83 %) had no malignant
      ventricular arrhythmia under medical therapy. 2 patients (17 %) required revision
      because of lead-dysfunction. In 2 patients with DCM the device was explanted
      during orthotopic heart transplantation. CONCLUSIONS: Our data demonstrate that
      advances in device- and leadtechnology have resulted in a decrease of severe
      complications in the pediatric age group. We conclude that ICD-implantation
      represents a safe and effective therapy for children and adolescents with
      lifethreatening ventricular dysrhythmias. Since it represents an invasive
      therapy, indication should be confined to patients with lifethreatening
      dysrhythmias according to the guidelines of the American Heart Association.

PMID- 16947096
TI  - [Use of transthoracic 3D-echocardiography in congenital heart disease].
AB  - 3D-echocardiography using a matrix array transducer was performed in 112
      patients. In 98 patients (87.5 %) we were able to acquire adequate 3D-data. The
      mean time for the 3D-examination was 5.5 min. In valve lesions, septal defects
      and complex cyanotic heart disease 3D-echocardiography was a confident and
      helpful innovation for better assessment of the intracardiac morphology in
      pediatric patients. We conclude that 3D-echocardiography is a useful addition to
      the conventional 2D-echocardiography.

PMID- 16947097
TI  - [Maternal tobacco consumption can be reduced by simple intervention of the
      paediatrician].
AB  - BACKGROUND: Exposure to environmental tobacco smoke at home increases the risk
      for numerous diseases in childhood. In this study we asked if maternal tobacco
      consumption can be reduced by a written advice of the paediatrician. PATIENTS AND
      METHODS: In a paediatrician's practice we recruited 40 mothers who smoked ten or
      more cigarettes per day according to their own statement. The paediatrician's
      intervention consisted in a short written advice to reduce tobacco consumption.
      At the beginning of the study and six weeks later we obtained urine samples of
      the mothers in order to measure the concentrations of the nicotine metabolite
      cotinine. A subgroup of the study population was informed about the initial
      concentration of cotinine, the other subgroup was not informed. MAIN RESULTS:
      Following the written advice of the paediatrician mothers reduced their
      consumption of tobacco products according to their own information as well as
      according to the concentrations of cotinine. Confronting mothers with their
      initial concentrations of cotinine was not found to be an additional factor
      reducing tobacco consumption. CONCLUSIONS: Maternal consumption of tobacco
      products can be reduced significantly by an advice of the paediatrician at least
      for a short time.

PMID- 16947098
TI  - [Fatigue and multiple sclerosis].

PMID- 16947099
TI  - [Measuring fatigue in patients with multiple sclerosis with standardized methods
      in German speaking areas].
AB  - Fatigue describes the presence of a pronounced and advanced state of weariness.
      People with fatigue need more energy and it takes more effort to perform
      different activities than expected when compared to the patients disability.
      Fatigue can be observed in up to 92 % of patients suffering from multiple
      sclerosis. In the presented study, the German fatigue severity scale (dFSS) was
      established following the English "Fatigue Severity Scale". We enrolled 20
      patients suffering from a primary relapsing multiple sclerosis and compared them
      to 20 healthy controls. Fatigue was detected if at least 4 points were reached in
      the dFSS. The dFSS demonstrated high validity and reliability. The dFSS is able
      to differentiate patients with fatigue from healthy controls. As consequence, the
      dFSS can be used to evaluate fatigue in German speaking individuals. The
      presented data demonstrated a good internal consistence. The scale is able to
      measure fatigue in an economic and rapid fashion. Therefore, it can be used in
      clinical situations for measuring fatigue in German speaking individuals.

PMID- 16947100
TI  - [A comparison of mother-child joint admission for postnatal mental disorders in
      different countries].
AB  - Postnatal depression is among the most frequent mental disorders in young women
      (incidence 10-15 %). Besides depressive illness, however anxiety disorder, stress
      disorder and psychosis play an important role as well. These disorders have not
      only negative impact on women's mental health, but may also adversely affect the
      child's development as well as the mother-child relationship. Inpatient mother
      child care as established e. g. at the Heidelberg University Hospital offers
      adequate treatment without the need for the mother to separate from her child. In
      a retrospective study a profile of the women treated at the Psychiatric
      Department of the University Hospital Heidelberg was developed which reflects the
      psychological and social stress in their life situations. In order to gain an
      overview on the specific treatment options the data were then compared with those
      of other national and international centres. Analysis of demand shows that this
      mother-child psychiatric care is well accepted by the population and that there
      is a considerable need for adequate in- and outpatient care of postnatal mental
      disorders.

PMID- 16947101
TI  - [Doble diagnosis--psychosis and addiction].

PMID- 16947102
TI  - Artificial selection on male longevity influences age-dependent reproductive
      effort in the black field cricket Teleogryllus commodus.
AB  - Although the trade-off between reproductive effort and longevity is central to
      both sexual selection and evolutionary theories of aging, there has been little
      synthesis between these fields. Here, we selected directly on adult longevity of
      male field crickets Teleogryllus commodus and measured the correlated responses
      of age-dependent male reproductive effort, female lifetime fecundity, and several
      other life-history traits. Male longevity responded significantly to five
      generations of divergent selection. Males from downward-selected lines commenced
      calling sooner and reached their peak calling effort at a younger age. They
      called more per night and, despite living less than half as long, called more
      overall than males selected for increased longevity. Females from the downward
      selected lines lived significantly shorter lives than females from the upward
      selected lines but still produced the same number of offspring. Nymph survival,
      development time, and body size and weight at eclosion did not show significant
      correlated response to selection on male longevity, despite evidence for
      substantial genetic variation in each of these traits. Collectively, our findings
      directly support the antagonistic pleiotropy model of aging and suggest an
      important role for sexual selection in the aging process.

PMID- 16947103
TI  - Encoding power in communication networks.
AB  - In animal societies, conflicts can be resolved by combatants or through third
      party intervention. In gregarious species, conflicts among pairs can spread to
      involve multiple individuals. In the case of large conflicts, containment and
      termination of aggression by third parties is important. Successful intervention
      relies on consensus among combatants about the intervener's capacity to use
      force. We refer to this consensus as power. We measure it and study how it
      arises, using as our model system a pigtailed macaque (Macaca nemestrina)
      society. In macaques, the degree to which one individual perceives another as
      capable of using force is communicated using a special dominance signal. Group
      consensus about an individual's capacity to use force arises from the network of
      signaling interactions. We derive a formalism to quantify consensus in the
      network. We find that the power distribution is fat tailed and power is a strong
      predictor of social variables including request for support, intervention cost,
      and intensity. We develop models to show how dominance-signaling strategies
      promote robust power distributions despite individual signaling errors. We
      suggest that when considering correlated interactions among many individuals it
      can be more useful to emphasize coarse-grained information stored at the group
      level--behavioral macrostates--over detailed information at the individual level.

PMID- 16947104
TI  - Host life-history strategy explains pathogen-induced sterility.
AB  - Virulence is often equated with pathogen-induced mortality, even though loss of
      fecundity is also common. But while the former may be understood as a simple
      consequence of lost host resources for the purposes of pathogen transmission,
      pathogen-induced sterility is often not associated with changes in host
      mortality. As a result, a separate literature has emerged to explain fecundity
      effects of parasitism that has not been integrated into general theories of the
      evolution of virulence. Here, I present a model of pathogen-induced sterility
      that is based on the assumption that hosts and pathogens vie for the same host
      resources for both reproduction and maintenance. Loss of host fecundity can then
      be explained by the host compensating for its future loss of resources, before
      infection. Such preinfection ;;fecundity compensation" may often cause
      preinfection investment in maintenance to be as low as postinfection levels,
      despite a loss of total host resources after infection. Thus, sterility is simply
      explained as a host life-history strategy in a system where the pathogen
      necessarily steals host resources for its own transmission. In certain
      circumstances, the pathogen may even be able to manipulate the host to redirect
      resources away from reproduction and toward maintenance through castration,
      causing gigantism.

PMID- 16947105
TI  - A gravity model for the spread of a pollinator-borne plant pathogen.
AB  - Many pathogens of plants are transmitted by arthropod vectors whose movement
      between individual hosts is influenced by foraging behavior. Insect foraging has
      been shown to depend on both the quality of hosts and the distances between
      hosts. Given the spatial distribution of host plants and individual variation in
      quality, vector foraging patterns may therefore produce predictable variation in
      exposure to pathogens. We develop a "gravity" model to describe the spatial
      spread of a vector-borne plant pathogen from underlying models of insect foraging
      in response to host quality using the pollinator-borne smut fungus Microbotryum
      violaceum as a case study. We fit the model to spatially explicit time series of
      M. violaceum transmission in replicate experimental plots of the white campion
      Silene latifolia. The gravity model provides a better fit than a mean field model
      or a model with only distance-dependent transmission. The results highlight the
      importance of active vector foraging in generating spatial patterns of disease
      incidence and for pathogen-mediated selection for floral traits.

PMID- 16947106
TI  - Can neutral theory predict the responses of Amazonian tree communities to forest
      fragmentation?
AB  - We use Hubbell's neutral theory to predict the impact of habitat fragmentation on
      Amazonian tree communities. For forest fragments isolated for about two decades,
      we generate neutral predictions for local species extinction, changes in species
      composition within fragments, and increases in the probability that any two trees
      within a fragment are conspecific. We tested these predictions using fragment and
      intact forest data from the Biological Dynamics of Forest Fragments Project in
      central Amazonia. To simulate complete demographic isolation, we excluded
      immigrants--species absent from a fragment or intact forest plot in the initial
      census but present in its last census--from our tests. The neutral theory
      correctly predicted the rate of species extinction from different plots as a
      function of the diversity and mortality rate of trees in each plot. However, the
      rate of change in species composition was much faster than predicted in
      fragments, indicating that different tree species respond differently to
      environmental changes. This violates the key assumption of neutral theory. When
      immigrants were included in our calculations, they increased the disparity
      between predicted and observed changes in fragments. Overall, neutral theory
      accurately predicted the pace of local extinctions in fragments but consistently
      underestimated changes in species composition.

PMID- 16947107
TI  - Population cycles produced by delayed density dependence in an annual plant.
AB  - In contrast to insect and animal populations, little attention has been directed
      to the study of cycles in plant populations. It has been argued on theoretical
      grounds that plants present stable dynamics. Nevertheless, there are examples
      where plant populations appear to exhibit oscillatory dynamics, but the
      oscillatory signal is variable and comes from very short time series data. Using
      a combination of time series, models, and empirical results, we present evidence
      of population cycles for Descurania sophia in a 16-year field experiment.
      Endogenous and exogenous causal mechanisms were studied to identify processes
      underlying this temporal dynamic. Our results show a 4-year cycle produced by
      delayed density dependence. We suggest that high nutrient levels might be
      responsible for the observed dynamics of D. sophia. Our results suggest that
      although plant population dynamics may be stabilized by direct density
      dependence, delayed density dependence could destabilize dynamics.

PMID- 16947108
TI  - Experimental evolution of phenotypic plasticity: how predictive are cross
      environment genetic correlations?
AB  - Genetic correlations are often predictive of correlated responses of one trait to
      selection on another trait. There are examples, however, in which genetic
      correlations are not predictive of correlated responses. We examine how well a
      cross-environment genetic correlation predicts correlated responses to selection
      and the evolution of phenotypic plasticity in the seed beetle Stator limbatus.
      This beetle exhibits adaptive plasticity in egg size by laying large eggs on a
      resistant host and small eggs on a high-quality host. From a half-sib analysis,
      the cross-environment genetic correlation estimate was large and positive
      (rA=0.99). However, an artificial-selection experiment on egg size found that the
      realized genetic correlations were positive but asymmetrical; that is, they
      depended on both the host on which selection was imposed and the direction of
      selection. The half-sib estimate poorly predicted the evolution of egg size
      plasticity; plasticity evolved when selection was imposed on one host but did not
      evolve when selection was imposed on the other host. We use a simple two-locus
      additive genetic model to explore the conditions that can generate the observed
      realized genetic correlation and the observed pattern of plasticity evolution.
      Our model and experimental results indicate that the ability of genetic
      correlations to predict correlated responses to selection depends on the
      underlying genetic architecture producing the genetic correlation.

PMID- 16947109
TI  - Phylogenetic analysis of the evolution of a signal of aggressive intent in
      northern swordtail fishes.
AB  - The initiation of a coevolutionary relationship between signal and response can
      be explained by either the receiver taking advantage of information inadvertently
      provided by the sender or the sender taking advantage of a perceptual bias in the
      receiver. In addition, once both signal and response are present, the exchange of
      information may or may not be cooperative. We examined the evolution of a signal
      of aggressive intent (expression of vertical bars) across all the northern
      swordtail fishes (Xiphophorus) in a phylogenetic context. We found that the
      signal was present before responses evolved, which suggests that this
      coevolutionary relationship was initiated by the receiver taking advantage of
      information inadvertently provided by the signaler. In addition, we introduce a
      novel method for examining the cooperative nature of signaling systems and
      provide some evidence to suggest that in this signaling system, receivers may be
      exploiting an honest signal in some species.

PMID- 16947110
TI  - Efficiency evaluation of two competing foraging modes under different conditions.
AB  - Various foraging modes are employed by predators in nature, ranging from ambush
      to active predation. Although the foraging mode may be limited by physiological
      constraints, other factors, such as prey behavior and distribution, may come into
      play. Using a simulation model, we tested to what extent the relative success of
      an ambush and an active predator changes as a function of the relative velocity
      and movement directionality of prey and active predator. In accordance with
      previous studies, we found that when both active predator and prey use
      nondirectional movement, the active mode is advantageous. However, as movement
      becomes more directional, this advantage diminishes gradually to 0. Previous
      theoretical studies assumed that animal movement is nondirectional; however,
      recent field observations show that in fact animal movement usually has some
      component of directionality. We therefore suggest that our simulation is a better
      predictor of encounter rates than previous studies. Furthermore, we show that as
      long as the active predator cannot move faster than its prey, it has little or no
      advantage over the ambush predator. However, as the active predator's velocity
      increases, its advantage increases sharply.

PMID- 16947111
TI  - Spatial scaling of consumer-resource interactions in advection-dominated systems.
AB  - Ecologists studying consumer-resource interactions in advection-dominated systems
      such as streams and rivers frequently seek to link the results of small-scale
      experiments with larger-scale patterns of distribution and abundance.
      Accomplishing this goal requires determining the characteristic scale, termed the
      response length, at which there is a shift from local dynamics dominated by
      advective dispersal to larger-scale dynamics dominated by births and deaths.
      Here, we model the dynamics of consumer-resource systems in a spatially variable,
      advective environment and show how consumer-resource interactions alter the
      response length relative to its single-species value. For one case involving a
      grazer that emigrates in response to high predator density, we quantify the
      changes using published data from small-scale experiments on aquatic
      invertebrates. Using Fourier analysis, we describe the responses of advection
      dominated consumer-resource systems to spatially extended environmental
      variability in a way that involves explicit consideration of the response length.
      The patterns we derive for different consumer-resource systems exhibit important
      similarities in how component populations respond to spatial environmental
      variability affecting dispersal as opposed to demographic parameters.

PMID- 16947112
TI  - Toward synthesis of relationships among leaf longevity, instantaneous
      photosynthetic rate, lifetime leaf carbon gain, and the gross primary production
      of forests.
AB  - The assimilation of carbon by plant communities (gross primary production [GPP])
      is a central concern in plant ecology as well as for our understanding of global
      climate change. As an alternative to traditional methods involving destructive
      harvests or time-consuming measurements, we present a simple, general model for
      GPP as the product of the lifetime carbon gain by a single leaf, the daily leaf
      production rate, and the length of the favorable period for photosynthesis. To
      test the model, we estimated leaf lifetime carbon gain for 26 species using the
      concept of mean labor time for leaves (the part of each day the leaf functions to
      full capacity), average potential photosynthetic capacity over the leaf lifetime,
      and functional leaf longevity (leaf longevity discounted for periods within a
      year wholly unfavorable for photosynthesis). We found that the lifetime carbon
      gain of leaves was rather constant across species. Moreover, when foliar biomass
      was regressed against functional leaf longevity, aseasonal and seasonal forests
      fell on a single line, suggesting that the leaf production rate during favorable
      periods is not substantially different among forests in the world. The gross
      production of forest ecosystems then can be predicted to a first approximation
      simply by the annual duration of the period favorable for photosynthetic activity
      in any given region.

PMID- 16947113
TI  - Migration dynamics for the ideal free distribution.
AB  - This article verifies that the ideal free distribution (IFD) is evolutionarily
      stable, provided the payoff in each patch decreases with an increasing number of
      individuals. General frequency-dependent models of migratory dynamics that differ
      in the degree of animal omniscience are then developed. These models do not
      exclude migration at the IFD where balanced dispersal emerges. It is shown that
      the population distribution converges to the IFD even when animals are nonideal
      (i.e., they do not know the quality of all patches). In particular, the IFD
      emerges when animals never migrate from patches with a higher payoff to patches
      with a lower payoff and when some animals always migrate to the best patch. It is
      shown that some random migration does not necessarily lead to undermatching,
      provided migration occurs at the IFD. The effect of population dynamics on the
      IFD (and vice versa) is analyzed. Without any migration, it is shown that
      population dynamics alone drive the population distribution to the IFD. If animal
      migration tends (for each fixed population size) to the IFD, then the combined
      migration-population dynamics evolve to the population IFD independent of the two
      timescales (i.e., behavioral vs. population).

PMID- 16947114
TI  - Life-history evolution in uncertain environments: bet hedging in time.
AB  - Many vertebrates, forest herbs, and trees exhibit both variable age at maturity
      and iteroparity as adaptations to uncertain environments. We analyze a stochastic
      model that combines these two life-history adaptations with density-dependent
      fertility. Results for a model with only iteroparity are consistent with previous
      work; environmental uncertainty favors adult survival over juvenile survival.
      This holds true even if there is a moderately strong convex trade-off between
      adult survival and fecundity, but the direction of selection can depend on which
      life-history trait is considered a random variable. A life history with only
      developmental delay favors juvenile survival in uncertain environments,
      consistent with previous models of seed banks. When both developmental delay and
      iteroparity are included in the model, both adaptations are favored in uncertain
      environments. Our simulations show that selection is not necessarily a runaway
      process in which either developmental delay or iteroparity is favored, as
      recently proposed by Tuljapurkar and Wiener, but rather that selection can favor
      both mechanisms. Invasion analysis shows that selective pressure on life-history
      delays increases as environmental variation increases. Reproductive delay and
      adult survival can be either adaptations or constraints. Natural-history studies
      that estimate model parameters can resolve this uncertainty.

PMID- 16947115
TI  - Mother-young recognition in an ungulate hider species: a unidirectional process.
AB  - Parent-offspring recognition is usually crucial for survival of young. In
      mammals, olfaction often only permits identification at short range, and
      vocalizations are important at longer distances. Following and hiding
      antipredator strategies found in newborn mammals may also affect parental
      recognition mechanisms. We investigated mother-offspring recognition in fallow
      deer, an ungulate hider species. We analyzed the structure of adult female and
      fawn contact calls to determine whether they are individually distinctive and
      tested for mother-offspring recognition. Only females (and not fawns) have
      individualized vocalizations, with the fundamental frequency as the most
      distinctive parameter. Playback experiments showed that fawns can distinguish the
      calls of their mothers from those of other females, but mothers could not
      discriminate their own and alien fawn calls. Thus, the vocal identification
      process is unidirectional. In followers, mother-offspring acoustic recognition is
      mutual, and therefore the different antipredator strategies of newborn mammals
      may have shaped the modalities of parent-offspring acoustic recognition.

PMID- 16947116
TI  - Evaluating thermoregulation in reptiles: an appropriate null model.
AB  - Established indexes of thermoregulation in ectotherms compare body temperatures
      of real animals with a null distribution of operative temperatures from a
      physical or mathematical model with the same size, shape, and color as the actual
      animal but without mass. These indexes, however, do not account for thermal
      inertia or the effects of inertia when animals move through thermally
      heterogeneous environments. Some recent models have incorporated body mass, to
      account for thermal inertia and the physiological control of warming and cooling
      rates seen in most reptiles, and other models have incorporated movement through
      the environment, but none includes all pertinent variables explaining body
      temperature. We present a new technique for calculating the distribution of body
      temperatures available to ectotherms that have thermal inertia, random movements,
      and different rates of warming and cooling. The approach uses a biophysical model
      of heat exchange in ectotherms and a model of random interaction with thermal
      environments over the course of a day to create a null distribution of body
      temperatures that can be used with conventional thermoregulation indexes. This
      new technique provides an unbiased method for evaluating thermoregulation in
      large ectotherms that store heat while moving through complex environments, but
      it can also generate null models for ectotherms of all sizes.

PMID- 16947117
TI  - Reporting of adverse drug reactions: predictors of under-reporting in Malaysia.
AB  - BACKGROUND: Malaysia like many other countries worldwide uses spontaneous
      reporting systems as a mean of collecting data on suspected adverse drug reaction
      (ADR). However, compared to other countries, which use the system, the reporting
      rate in Malaysia is very low. Why some physicians do not report ADRs is not well
      understood. OBJECTIVE: To identify factors, which would predict physicians'
      failure to send ADR reports. DESIGN AND SETTING: Face-to-face interview using a
      structured questionnaire involving physicians working at the University of Malaya
      Medical Centre, Malaysia. RESULTS: About a third of the physicians in the Centre
      participated. Sixty-five of the 415 approached refused to participate. A high
      proportion of the respondents (81.4%) indicated that they had suspected an ADR
      but did not report it, while about 40% of the respondents were not aware of the
      existence of the national reporting system in Malaysia. Logistic regression
      modelling identified the variable 'ADR considered to be too trivial or too well
      known to report' as the strongest predictor of not reporting, followed by
      physicians' category and uncertainty that the reaction had been definitely caused
      by a drug. CONCLUSION: Important predictor variables, which limit physicians from
      reporting ADR in Malaysia, were related to uncertainty of types of reaction to
      report, lack of awareness about the existence, function and purpose of national
      ADR reporting. The findings could be useful for planning strategies to improve
      the reporting rate.

PMID- 16947118
TI  - Comparative proteomic studies on the pathogenesis of human ulcerative colitis.
AB  - Ulcerative colitis (UC) is a chronic inflammatory disorder primarily affecting
      the colon mucosa. Its etiology and pathogenesis remain unclear. We used 2-DE and
      MS to identify differentially expressed proteins among the UC active, UC
      inactive, nonspecific colitis, and normal colon mucosa. Thirteen down-regulated
      and six up-regulated proteins were identified. Of the down-expressed proteins,
      eight (heat-shock protein 90 (HSPA9B), heat-shock protein 60 (HSPD1), H+
      transporting two-sector ATPase (ATP5B), prohibitin (PHB), mitochondrial malate
      dehydrogenase (MDH2), voltage-dependent anion-selective channel protein 1
      (VDAC1), thioredoxin peroxidase (PRDX1), and thiol-specific antioxidant (PRDX2))
      were mitochondrial proteins, three (ATP5B, MDH2, triosephosphate isomerase) were
      involved in energy generation, three (PRDX1, PRDX2, SELENBP1) were cellular
      antioxidants, and six (HSPD1, HSPA9B, PRDX1, PRDX2, PHB, VDAC1) were stress
      response proteins. Transmission electron microscopy revealed pathological
      alterations of mitochondrial ultrastructures even before the global colonocyte
      changes in the UC colon mucosa. PHB, an essential mitochondrial component
      protein, was down-expressed in the disease active as well as inactive colon
      mucosa from the patients of UC, indicative of an early event of mitochondrial
      changes during UC development. In contrast, aberrant activation of NFAT and
      ectopic expression of potential immunogenic proteins (tumor rejection antigen 1
      and poliovirus receptor related protein 1) were found in the UC-diseased colon
      mucosa. Our findings suggest the implications of colonocyte mitochondrial
      dysfunction and perturbed mucosa immune regulation in the pathogenesis of UC and
      provide potential targets for the development of a new therapy.

PMID- 16947119
TI  - Effect of fungal polysaccharides on the modulation of plasma proteins in
      streptozotocin-induced diabetic rats.
AB  - To search out novel biomarkers for monitoring diabetes prognosis, we examined the
      effect of hypoglycemic fungal exopolysaccharides (EPS) on the differential levels
      of plasma proteins in streptozotocin-induced diabetic rats. The orally
      administrated EPS exhibited an excellent hypoglycemic effect, lowering the
      average plasma glucose level, and increasing insulin secretion in diabetic rats.
      The 2-DE analysis of rat plasma demonstrated that about 500 visualized spots were
      differentially regulated, of which 20 spots were identified as principal diabetes
      associated proteins. The distinct effect of diabetes induction on the pattern of
      rat plasma proteins includes the down-regulation of albumin, apolipoprotein E
      (Apo E), alpha1-inhibitor-3, fetuin beta, Gc-globulin, hemopexin, vitronectin,
      and transthyretin (TTR) monomer, and the up-regulation of Apo A-I, Apo A-IV,
      ceruloplasmin, alpha1-antitrypsin, serine protease inhibitor III, and
      transferrin. Those protein levels were interestingly restored to those of healthy
      rats by EPS treatment, although the order of magnitude of the changes differed
      widely. Two proteins of interest showed distinct differential expression with
      opposite trends: TTR tetramer was significantly down-regulated and immunoglobulin
      (Ig) kappa light chain was significantly up-regulated upon diabetes induction,
      both of which were also normalized to those of healthy groups after EPS
      treatment.

PMID- 16947120
TI  - Proteomic analysis of individual variation in normal livers of human beings using
      difference gel electrophoresis.
AB  - Normal Chinese Liver Proteome Expression Profile is one of the major parts of
      Human Liver Proteome Project. Before starting the studies, it is necessary to
      examine the interindividual variation of normal liver proteome and evaluate the
      minimal size of samples for proteomic analysis. In this study, normal liver
      samples from ten individual volunteers were collected and the proteome profiles
      of these samples were analyzed using 2-D difference gel electrophoresis (DIGE)
      combined with MALDI-TOF/TOF MS. The individual liver tissue lysates were labeled
      with Cy3 and Cy5 while the pooled sample was labeled with Cy2 as an internal
      standard, which minimized gel-to-gel variation. After analysis by the DeCyder
      software, up to 2056 protein spots were detected on the master gel. The CV of
      standardized abundance was calculated for the protein spots that were matched
      across all ten gels. The CV values of these protein spots ranged from 6.4 to
      108.5% and the median CV was approximately 19%, which demonstrated that the
      protein expression of normal liver among different individuals was relatively
      stable. The eight proteins with CV values over 50% were identified which would be
      a caveat when considering these proteins as potential disease-related markers.
      Moreover, the one-way ANOVA feature showed a correlation between sample size and
      individual variations. The results showed that when the sample size exceeded 7,
      the individual variations were not significant to the whole pool. Our results are
      an important basis for liver protein expression profiles and comparative
      proteomics of liver disease.

PMID- 16947121
TI  - Proteome analysis of B-cell maturation.
AB  - Proteins affected by anti-mIgM stimulation during B-cell maturation were
      identified using 2-DE-based proteomics. We investigated the proteome profiles of
      stimulated and nonstimulated Ramos B-cells at eight time points during 5 d and
      compared the obtained proteomic data to the corresponding data from DNA
      microarray studies. Anti-mIgM stimulation of the cells resulted in significant
      differences (> or =twofold) in the protein abundance close to 100 proteins and
      differences in post-translational protein modifications. Forty-eight up- or down
      regulated proteins were identified by mass spectrometric methods and database
      searches. The identities of a further nine proteins were revealed by comparing
      their positions to the known proteins in other lymphocyte 2-DE databases. Several
      of the proteins are directly related to the functional and morphological
      characteristics of B-cells, such as cytoskeleton rearrangement and intracellular
      signalling triggered by the crosslinking of B-cell receptors. In addition to
      proteins known to be involved in human B-cell maturation, we identified several
      proteins that were not previously linked to lymphocyte differentiation. The
      results provide deeper insights into the process of B-cell maturation and may
      lead to novel therapeutic strategies for immunodeficiencies. An interactive 2-DE
      reference map is available at http://bioinf.uta.fi/BcellProteome.

PMID- 16947122
TI  - An integrated approach to mapping the proteome of the human bone marrow stromal
      cell.
AB  - Bone marrow stromal cells, also known as mesenchymal stem or progenitor cells,
      are thought to play a critical role in hematopoiesis. Because hematopoiesis is
      dysregulated in leukemic individuals, expression profiling in leukemic stromal
      cells might yield valuable insights into mechanisms of normal and dysregulated
      hematopoiesis. Here, proteomics was used to identify expressed proteins in normal
      and leukemic bone marrow stromal cells. Isobaric tags for relative and absolute
      quantification (iTRAQ) technology and MS/MS were used to identify and quantify
      proteins in bone marrow stromal cells from two normal and two leukemic
      individuals. Approximately 900 distinct proteins were identified with >95%
      confidence, 73 of which were differentially expressed in leukemic stromal cells.
      cDNA microarray analysis on Affymetrix oligonucleotide gene chips showed that
      transcripts correlated with approximately 90% of the expressed proteins. A novel
      integrated approach for mining and visualization of iTRAQ data is presented. The
      results provide an initial assessment of the proteome in human bone marrow
      stromal cells, laying the groundwork for comprehensive analysis of the proteome
      in these cells, and ultimately, for improved understanding of normal and
      dysregulated hematopoiesis.

PMID- 16947123
TI  - A differentially expressed proteomic analysis in placental tissues in relation to
      pungency during the pepper fruit development.
AB  - Using proteomic analysis including 2-DE, image analysis, and protein
      identification with LC-MS/MS, an investigation aimed at a better understanding of
      the differentially expressed proteins and/or gene products was carried out with
      total cell extracts from placental tissues in nonpungent (Capsicum annuum cv.
      Saeng-Ryeog #213) and pungent peppers (C. annuum cv. Saeng-Ryeog #211).
      Mobilization of the most abundant proteins, which were on the gels of pH ranges
      of 4-7, 4.5-5.5, 5.5-6.7, and 6-9, and showed very similar profiles in the two
      tissues, revealing approximately 2600 protein spots consisting of 1200 on pH 4-7,
      600 on 4.5-5.5, 550 on 5.5-6.7, 250 on 6-9. Of these, 37 protein spots, which
      appeared in only pungent tissues but not in nonpungent tissues or markedly
      increased in their staining intensities on the gels from pungent tissue, were
      selected, excised, in-gel trypsin digested, and analyzed by LC-ESI-MS/MS. Peptide
      MS/MS data were searched against publicly available protein and EST databases,
      and 22 proteins were identified. Based on this result, we tested and compared the
      differential expression during fruit development on the 2-DE gels with total cell
      extracts from placental tissues of pungent and nonpungent peppers at an interval
      of 10 days from 10 to 40 days after flowering. In addition, this differential
      protein expression was further confirmed for some subsets of candidates by
      Northern-blot analysis with RNA samples from placental tissues harvested from
      each pepper fruit at the same sampling intervals. In this study, the
      physiological implications, revealed from the experimental data in the levels of
      proteome and transcripts, are discussed in the context of a complex biosynthesis
      network of capsaicinoids in pepper cells responsive to pungency.

PMID- 16947139
TI  - The design of simulation studies in medical statistics.
AB  - Simulation studies use computer intensive procedures to assess the performance of
      a variety of statistical methods in relation to a known truth. Such evaluation
      cannot be achieved with studies of real data alone. Designing high-quality
      simulations that reflect the complex situations seen in practice, such as in
      prognostic factors studies, is not a simple process. Unfortunately, very few
      published simulation studies provide sufficient details to allow readers to
      understand fully all the processes required to design a simulation study. When
      planning a simulation study, it is recommended that a detailed protocol be
      produced, giving full details of how the study will be performed, analysed and
      reported. This paper details the important considerations necessary when
      designing any simulation study, including defining specific objectives of the
      study, determining the procedures for generating the data sets and the number of
      simulations to perform. A checklist highlighting the important considerations
      when designing a simulation study is provided. A small review of the literature
      identifies the current practices within published simulation studies.

PMID- 16947202
TI  - Power and sample size calculations for discrete bounded outcome scores.
AB  - We consider power and sample size calculations for randomized trials with a
      bounded outcome score (BOS) as primary response adjusted for a priori chosen
      covariates. We define BOS to be a random variable restricted to a finite
      interval. Typically, a BOS has a J- or U-shaped distribution hindering
      traditional parametric methods of analysis. When no adjustment for covariates is
      needed, a non-parametric test could be chosen. However, there is still a problem
      with calculating the power since the common location-shift alternative does not
      hold in general for a BOS. In this paper, we consider a parametric approach and
      assume that the observed BOS is a coarsened version of a true BOS, which has a
      logit-normal distribution in each treatment group allowing correction for
      covariates. A two-step procedure is used to calculate the power. Firstly, the
      power function is defined conditionally on the covariate values. Secondly, the
      marginal power is obtained by averaging the conditional power with respect to an
      assumed distribution for the covariates using Monte Carlo integration. A
      simulation study evaluates the performance of our method which is also applied to
      the ECASS-1 stroke study.

PMID- 16947229
TI  - 16th World Congress on Ultrasound in Obstetrics and Gynecology, 3-7 September
      2006, London, UK. Abstracts.

PMID- 16947273
TI  - Comparing correlations of continuous observations from two independent
      populations using a sequential approach.
AB  - A sequential study design generally makes more efficient use of available
      information than a fixed sample counterpart of equal power. This feature is
      gradually being exploited by researchers in genetic and epidemiological
      investigations that utilize banked biological resources and in studies where
      time, cost and ethics are prominent considerations. Recent work in this area has
      focussed on the sequential analysis of matched case-control studies with a
      dichotomous trait. In this paper, we extend the sequential approach to a
      comparison of the associations within two independent groups of paired continuous
      observations. Such a comparison is particularly relevant in familial studies of
      phenotypic correlation using twins. We develop a sequential twin method based on
      the intraclass correlation and show that use of sequential methodology can lead
      to a substantial reduction in the number of observations without compromising the
      study error rates. Additionally, our approach permits straightforward allowance
      for other explanatory factors in the analysis. We illustrate our method in a
      sequential heritability study of dysplasia that allows for the effect of body
      mass index and compares monozygotes with pairs of singleton sisters.

PMID- 16947300
TI  - A proteomic analysis during serial subculture and osteogenic differentiation of
      human mesenchymal stem cell.
AB  - Although previous studies have reported the effects of extensive subculturing on
      proliferation rates and osteogenic potential of human mesenchymal stem cells
      (hMSCs), the results remain controversial. The aim of our study was to
      characterize the proliferation and osteogenic potential of hMSCs during serial
      subculture, and also to identify proteins that are differentially regulated in
      hMSCs during serial subculture and osteogenic differentiation using proteome
      analysis. Here we show that the proliferation and osteogenic capacity of hMSCs
      decrease during serial subculturing. Several proteins were shown to be
      differentially regulated during serial subculture; among these the expression of
      T-complex protein 1 alpha subunit (TCP-1alpha), a protein known to be associated
      with cell proliferation, cell cycle, morphological changes, and apoptosis,
      gradually decreased during serial subculture. Among proteins that were
      differentially regulated during osteogenic differentiation, chloride
      intracellular channel 1 (CLIC1) was downregulated only during the early passages
      eukaryotic translation elongation factor, and acidic ribosomal phosphoprotein P0
      was downregulated during the middle passages, while annexin V, LIM, and SH3
      domain protein 1 (LASP-1), and 14-3-3 protein gamma (YWHAG) were upregulated
      during the later passage. These studies suggest that differentially regulated
      passage-specific proteins may play a role in the decrease of osteogenic
      differentiation potential under serial subculturing.

PMID- 16947312
TI  - Involvement of complement receptor 3 (CR3) and scavenger receptor in macrophage
      responses to wear debris.
AB  - The ability of prosthetic wear debris to induce pro-inflammatory responses in
      macrophages is widely appreciated, but little is known about the molecular
      mechanisms involved in particle recognition. Specifically, the nature of the cell
      surface receptors that interact with wear debris is poorly understood.
      Elucidating the identities of these receptors and how they interact with
      different types of wear debris are critical to understanding how wear debris
      initiates periprosthetic osteolysis. We examined the involvement of opsonization,
      complement receptor 3 (CR3), and scavenger receptor A (SRA), in responses to
      polymethylmethacrylate (PMMA) and titanium wear particles. Serum dependence of
      pro-inflammatory responses to PMMA and titanium was tested, and serum proteins
      that adhered to these two types of particles were identified. Several serum
      proteins, including known opsonins such as C3bi and fibronectin, adhered to PMMA
      but not titanium, and serum was required for pro-inflammatory signaling induced
      by PMMA, but not by titanium. Phagocytosis of PMMA and titanium by macrophages
      was demonstrated by flow cytometry. Blocking CR3 specifically inhibited
      phagocytosis of PMMA by macrophages, whereas blocking SRA specifically inhibited
      titanium uptake. Direct involvement of CR3 and SRA in cell-particle interaction
      was assessed by expression of these receptors in nonphagocytic HEK293 cells. CR3
      specifically induced cell binding to PMMA particles and adhesion to PMMA-coated
      plates, while SRA specifically induced binding to titanium particles and adhesion
      to titanium-coated plates. Taken together, these results suggest involvement of
      opsonization, complement, and integrin receptors, including CR3 and fibronectin
      receptors, in PMMA action, and an involvement of scavenger receptors in responses
      to titanium.

PMID- 16947313
TI  - MRI of the kidney and urinary tract.
AB  - MRI of the kidney and urinary tract has evolved with advancements in MR
      technology combined with further radiologic experience. A combination of simple
      pulse sequences and the use of gadolinium (Gd) allow a comprehensive evaluation
      of the genitourinary system and facilitate the detection and accurate
      characterization of renal and urinary tract masses. In this review an MRI
      technique used to evaluate the kidneys and urinary tract is presented with an
      emphasis on the characterization of renal masses.

PMID- 16947314
TI  - Pure red cell aplasia caused by antibody to erythropoietin successfully treated
      by cyclosporine administration.

PMID- 16947315
TI  - A case of Waldenstrom's macroglobulinemia preceeded by larynx carcinoma.

PMID- 16947316
TI  - Combined D-dimer and clinical probability are useful for exclusion of recurrent
      deep venous thrombosis.
AB  - It is estimated that up to one-third of patients with a history of deep venous
      thrombosis (DVT) present with symptoms of recurrent DVT. Our objective was to
      investigate both the diagnostic value of D-dimer (DD) and safety of a standard
      diagnostic algorithm including clinical assessment, plasma DD levels, and
      compression venous ultrasound as diagnostic tools in outpatients presenting with
      clinically suspected acute recurrent DVT of the lower limbs. We have enrolled 105
      outpatients with a previous history of confirmed DVT and clinically suspected
      recurrent DVT. A 3-month follow-up period was carried out for patients in whom
      DVT was initially excluded. Prevalence of DVT in our study population was 44.8%
      (47/105). DD was negative in 17.1% of cases (18/105) and DVT could be ruled out
      in 15.2% of patients evaluated (16/105) on the basis of an unlikely clinical
      probability and a negative DD result. Only one false negative DD result in a
      patient scored as likely for DVT was found. Sensitivity, specificity, positive
      and negative predictive value of DD for the diagnosis of DVT were 97.9% (95% CI
      88.9-99.6%), 29.3% (95% CI 19.2-42.0%), 52.9% (95% CI 42.5-63.0) and 94.4% (95%
      CI 74.2%-99.0), respectively. Sensitivity was 100% (95% CI 75.7-100) in the group
      of patients in whom DVT was considered unlikely. A diagnostic strategy combining
      clinical evaluation and DD has proved to be useful for the exclusion of DVT in
      subjects with clinically suspected recurrent DVT, especially in patients included
      in the lower clinical pretest probability group.

PMID- 16947317
TI  - Acute myeloid leukemia with T-cell receptor gamma gene rearrangement occurring in
      a patient with chronic lymphocytic leukemia: a case report.
AB  - The association of chronic lymphocytic leukemia (CLL) and acute leukemia, either
      lymphoid or myeloid is a rare event. Our review of the medical literature
      revealed only 6 cases of CLL transformation to acute myeloid leukemia (AML) (M0,
      M1 and M2) with no other associated malignancy. We report a similar case but with
      occurrence of AML-M4 associated with normal cytogenetic analysis and molecular
      testing but with positive T-cell receptor gamma gene rearrangement rather than
      the usual Vbeta rearrangement.

PMID- 16947318
TI  - Preclinical assessment of curcumin as a potential therapy for B-CLL.
AB  - Curcumin, the principle component of the spice turmeric, has been used as an anti
      inflammatory medication in India and China for centuries. Recent studies,
      predominantly using actively dividing cell lines, have suggested that this
      compound could be used as a chemopreventative or therapeutic agent for epithelial
      tumors. As curcumin has been reported to inhibit the NIK/IKK complex, an activity
      that would be expected to induce apoptosis in B cell malignancies, we sought to
      determine whether curcumin induces apoptosis in vitro in primary chronic
      lymphocytic leukemia (B-CLL) cells. Primary leukemic cells were incubated with
      varying dosages of curcumin, followed by assessment for apoptosis. The role of
      PPARgamma or NF-kappaB signaling in curcumin-induced apoptosis was examined by
      cotreatment with a PPARgamma antagonist or EMSA of nuclear NFkappaB complexes. We
      also examined whether a clinically achievable concentration of curcumin (1
      microM) would augment the apoptotic effects of fludarabine, dexamethasone,
      vincristine or the PDE4 inhibitor rolipram. In B-CLL cells from 14 patients,
      curcumin-induced apoptosis with a mean EC(50) of 5.5 microM. In contrast, the
      EC(50) for whole mononuclear cells from a healthy donor was 21.8 microM. In a 48
      hr wash-out time course, curcumin-induced apoptosis was time-dependent, with a
      substantial reduction in apoptosis observed when curcumin was removed after 5 hr.
      Curcumin treatment reduced basal nuclear NF-kappaB levels and 1 microM curcumin
      augmented both vinca alkaloid and PDE4 inhibitor-induced apoptosis in B-CLL
      cells. Our studies suggest that curcumin may augment the efficacy of established
      or experimental therapies for B-CLL.

PMID- 16947319
TI  - Timing of allogeneic BMT for CML patients in India: does it affect response?

PMID- 16947320
TI  - Reversible posterior leukoencephalopathy syndrome after repeat intermediate-dose
      cytarabine chemotherapy in a patient with acute myeloid leukemia.
AB  - A 56-year-old man was admitted to our hospital with leukocytosis, anemia, and
      thrombocytopenia. Acute monoblastic leukemia was diagnosed. Two subsequent
      courses of consolidation chemotherapy consisted of conventional doses of
      cytarabine and intermediate-dose cytarabine. Intermediate-dose cytarabine was
      infused intravenously every 12 hr for 6 days. On day 15 after the final infusion
      of cytarabine, the patient suffered headache, and on day 21, he experienced a
      decrease in sensation on the sole of his left foot. Magnetic resonance imaging
      (MRI) of the brain revealed widespread areas of white matter edema. Cerebrospinal
      fluid (CSF) examination revealed an increase in the number of cells to 31 mm(-3);
      the majority were lymphocytes. No infiltration of leukemia cells was seen. After
      2 months, brain MRI findings were normal. The clinicoradiologic features of the
      case were consistent with reversible posterior leukoencephalopathy syndrome
      (RPLS). RPLS in the present case was unlikely to have been caused by direct
      neurotoxicity because (1) the doses of cytarabine (500 mg/m(2); total dose 9.2 g)
      were much smaller than those in reported cases and were repeatedly infused until
      RPLS developed; (2) the RPLS developed 21 days after the final infusion of
      cytarabine, a much longer period than previously reported; (3) the slight
      leukocytosis in the CSF observed on day 33 might also have been related to the
      cellular immune responses evoked by the infused cytarabine. These details suggest
      not only that direct cerebral neurotoxicity of cytarabine but also that some type
      of allergic response may have been involved in the development of RPLS.

PMID- 16947321
TI  - Disseminated extramedullary myeloid tumor of the gallbladder without involvement
      of the bone marrow.
AB  - Extramedullary myeloid tumors (myeloid sarcomas) are rare neoplasms that are
      composed of myeloid precursors. They usually arise concurrently with a diagnosis
      of acute myeloid leukemia, chronic myeloid leukemia, or other myeloproliferative
      disorders. They may also indicate relapsing disease in a patient with a prior
      history of leukemia or myeloproliferative disorder. We present our findings of a
      63-year-old female diagnosed with extramedullary myeloid tumor first presenting
      in the gallbladder. She subsequently developed respiratory failure; pre- and
      postmortem bone marrow studies were negative for leukemia by morphology, flow
      cytometry, and karyotypic analysis. However, the myeloid neoplasm was
      disseminated throughout most of her remaining organs. Immunohistochemical stains
      of the cells indicated a neoplasm of myelomonocytic derivation (CD4, CD43, CD45,
      CD68, myeloperoxidase, and lysozyme positive). To our knowledge, this is the
      first report of an extramedullary myeloid neoplasm of the gallbladder with
      disseminated disease without involvement of the bone marrow.

PMID- 16947323
TI  - Suspected cardiac amyloidosis: endomyocardial biopsy remains the diagnostic gold
      standard.

PMID- 16947325
TI  - Detailed analysis of myocardial motion in volunteers and patients using high
      temporal-resolution MR tissue phase mapping.
AB  - PURPOSE: To detect and investigate details in left ventricular (LV) motion
      patterns with a temporal resolution comparable to that of echocardiography.
      MATERIAL AND METHODS: To assess global and regional myocardial motion in high
      temporal detail, respiratory-gated MR phase-contrast measurements with three
      directional velocity encoding (venc) were performed in 12 healthy volunteers and
      two patients with LV hypertrophy in basal, midventricular, and apical locations
      of the LV with a temporal resolution of 13.8 msec. RESULTS: The volunteer data
      revealed details in LV motion patterns that were known only from
      echocardiography. For all volunteers, characteristic myocardial motion patterns,
      such as triphasic global diastolic expansion, could be detected with high
      accuracy. One volunteer underwent an additional echocardiographic measurement in
      order to corroborate the complex motion features as measured by MRI. Patient
      examinations revealed substantial changes in diastolic function compared to
      motion patterns in healthy volunteers. CONCLUSION: The proposed high-temporal
      resolution velocity-mapping technique provides previously undetectable
      information on LV performance, and is highly promising for the detection of local
      and global motion abnormalities in patients with disturbed LV performance, such
      as diastolic dysfunction.

PMID- 16947328
TI  - Cellular properties of human erythrocytes preserved in saline-adenine-glucose
      mannitol in the presence of L-carnitine.
AB  - L-Carnitine (LC) in the preservation medium during storage of red blood cells
      (RBC) can improve the mean 24-hr percent recovery in vivo and increase RBC life
      span after reinfusion. The purpose of the study was to investigate the
      differences in the biochemical properties of RBCs stored in the presence or
      absence of LC, and the cell-age related responses to storage conditions and to
      LC. RBC concentrates in saline-adenine-glucose-mannitol (SAG-M) were stored in
      the presence or absence of 5 mM LC at 4 degrees C for up to 8 weeks. RBC
      subpopulations of different densities were prepared by centrifugation on Stractan
      density gradient. Cells were sampled at 0, 3, 6, and 8 weeks, and hematological
      and cellular properties analyzed (MCV, MCHC, 4.1a/4.1b ratio as a cell age
      parameter, intracellular Na(+) and K(+)). After 6 weeks, MCV of RBC stored in the
      presence of LC was lower than that of controls (6 weeks MCV: controls 95.4 +/-
      1.8 fl; LC 91.5 +/- 2.0 fl; n = 6; P < 0.005). This was due to swelling of
      control cells, and affected mainly older RBCs. LC appeared to reduce or retard
      cell swelling. Among the osmotically active substances whose changes during
      storage could contribute to cell swelling, only intracellular Na(+) and K(+)
      differed between stored control RBCs and LC-treated cells. LC reduces the
      swelling of older cells during storage at 4 degrees C in SAG-M, possibly by
      acting on the permeability of cell membrane to monovalent cations.

PMID- 16947339
TI  - Focal nodular hyperplasia: lesion characteristics on state-of-the-art MRI
      including dynamic gadolinium-enhanced and superparamagnetic iron-oxide-uptake
      sequences in a prospective study.
AB  - PURPOSE: To image a cohort of patients with pathology-proven focal nodular
      hyperplasia (FNH) to assess which characteristics of state-of-the-art magnetic
      resonance imaging (MRI) of the liver are the most useful for improving the
      detection and characterization of FNH. MATERIALS AND METHODS: In 14 patients,
      pathology-proven FNH (N=33) were prospectively examined using gadolinium (Gd) and
      superparamagnetic iron-oxide (SPIO) contrast media. All lesions were evaluated
      for signal intensity (SI), fatty infiltration, central scar, mode of enhancement
      with Gd, and uptake of SPIO. The percentage of dynamic contrast enhancement in
      the arterial, portal, and delayed phases was assessed. The contrast-to-noise
      ratio (CNR) before and after administration of SPIO contrast was calculated.
      RESULTS: The SI of the lesions was low to isointense on T1-weighted (T1W) images,
      and intermediate to isointense on T2W images. Fatty infiltration of the lesions
      was present in 6%. The percentages of enhancement in the liver and lesion were
      110%, 115%, and 95%, and 151%, 182%, and 160%, respectively (P<0.0001). All
      lesions showed uptake of SPIO with improved conspicuity of the central scar and
      septa. The CNR values precontrast and post-Gd/SPIO were significantly different
      for T1 in- and opposed-phase and black-blood echo-planar imaging (BBEPI).
      CONCLUSION: Combining dynamic Gd-enhanced imaging with T1W and T2W sequences
      after administration of SPIO facilitates comprehensive evaluation of FNH.

PMID- 16947341
TI  - MP-SAGE: A new MP-RAGE sequence with enhanced SNR and CNR for brain imaging
      utilizing square-spiral phase encoding and variable flip angles.
AB  - The magnetization-prepared rapid gradient-echo (MP-RAGE) sequence is well known
      and widely used for high-resolution, structural brain MRI. Here we present a new
      version, termed magnetization-prepared spiral acquisition gradient-echo (MP
      SAGE), that employs interleaved square-spiral phase-encoding (PE) to take
      advantage of the 3D nature of the sequence. Resolution loss caused by point
      spread function (PSF) blurring is circumvented by the use of variable flip angle
      (VFA) radiofrequency (RF) pulses. The pulse train is calculated by means of an
      accurate new signal evolution theory that is derived from the extended phase
      graph (EPG) description. Phantom results show excellent agreement between theory
      and experiment for substances with relaxation times similar to those of human
      brain tissue. Both phantom and in vivo results show a strong enhancement of SNR
      and CNR compared to the standard MP-RAGE in high-resolution MRI. The benefits for
      brain tissue segmentation using images obtained with MP-SAGE are shown.

PMID- 16947380
TI  - Quantification of the pulse wave velocity of the descending aorta using axial
      velocity profiles from phase-contrast magnetic resonance imaging.
AB  - The pulse wave velocity (PWV) of aortic blood flow is considered a surrogate for
      aortic compliance. A new method using phase-contrast (PC)-MRI is presented
      whereby the spatial and temporal profiles of axial velocity along the descending
      aorta can be analyzed. Seventeen young healthy volunteers (the YH group), six
      older healthy volunteers (the OH group), and six patients with coronary artery
      disease (the CAD group) were studied. PC-MRI covering the whole descending aorta
      was acquired, with velocity gradients encoding the in-plane velocity. From the
      corrected axial flow velocity profiles, PWV was determined from the slope of an
      intersecting line between the presystolic and early systolic phases. Furthermore,
      the aortic elastic modulus (Ep) was derived from the ratio of the brachial pulse
      pressure to the strain of the aortic diameter. The PWV increased from YH to OH to
      CAD (541 +/- 94, 808 +/- 184, 1121 +/- 218 cm/s, respectively; P = 0.015 between
      YH and OH; P = 0.023 between OH and CAD). There was a high correlation between
      PWV and Ep (r = 0.861, P < 0.001). Multivariate analysis showed that age and CAD
      were independent risk factors for an increase in the PWV. Compared to existing
      methods, our method requires fewer assumptions and provides a more intuitive and
      objective way to estimate the PWV.

PMID- 16947381
TI  - Dysregulation of interleukin-10-dependent gene expression in rheumatoid arthritis
      synovial macrophages.
AB  - OBJECTIVE: The inflammatory cytokines tumor necrosis factor alpha (TNFalpha) and
      interleukin-1 (IL-1) are produced by activated macrophages, are key mediators of
      pathogenesis, and are validated therapeutic targets in rheumatoid arthritis (RA)
      and seronegative spondylarthritis (SpA). IL-10 is a potent antiinflammatory
      cytokine that suppresses macrophage TNFalpha and IL-1 production, yet is not
      effective in suppressing inflammatory arthritis. To gain insight into IL-10
      responses in inflammatory arthritis, we used microarray analysis to determine the
      patterns of IL-10-inducible gene expression in freshly isolated RA and
      seronegative SpA synovial macrophages. METHODS: Macrophages from the synovial
      fluid of 5 patients with RA and 3 with seronegative SpA (2 with psoriatic
      arthritis and 1 with ankylosing spondylitis) were isolated by positive selection
      and stimulated ex vivo with IL-10 or interferon-gamma (IFNgamma). Gene expression
      was analyzed using Affymetrix microarrays and protocols. Real-time polymerase
      chain reaction was used to confirm changes in gene expression. RESULTS: The
      number of genes induced by IL-10 in arthritic macrophages was markedly smaller
      than that induced in control macrophages, and the strength of induction was lower
      in arthritic macrophages for most genes. The residual response of arthritic
      macrophages to IL-10 stimulation was qualitatively altered, such that IL-10
      preferentially increased expression of IFNgamma-inducible genes. In contrast,
      arthritic macrophages expressed many IFNgamma-inducible genes prior to
      stimulation, and their response to IFNgamma remained mostly intact. CONCLUSION:
      These results demonstrate that IL-10 responses are dysregulated in RA synovial
      macrophages. An altered biologic response to IL-10, with attenuation of its
      antiinflammatory function and a concomitant retention of IFNgamma-like activating
      functions, provides a basis for the lack of efficacy of IL-10 in suppressing
      inflammatory arthritis.

PMID- 16947382
TI  - Up-regulated transforming growth factor beta-inducible gene h3 in rheumatoid
      arthritis mediates adhesion and migration of synoviocytes through alpha v beta3
      integrin: Regulation by cytokines.
AB  - OBJECTIVE: To delineate the expression of transforming growth factor beta
      inducible gene h3 (betaIG-H3) in rheumatoid synovitis and to determine the
      regulatory role of betaIG-H3 in the adhesion and migration of fibroblast-like
      synoviocytes (FLS). METHODS: Synovial tissue was obtained from patients with
      rheumatoid arthritis (RA) during joint replacement surgery, and FLS were isolated
      using enzymatic treatment. Immunohistochemical staining was performed to show the
      expression of betaIG-H3 within rheumatoid synovium. Synthesis of betaIG-H3 from
      FLS was determined by semiquantitative reverse transcription-polymerase chain
      reaction, Western blot analysis, and enzyme-linked immunosorbent assay. Cell
      adhesion and migration assays were performed using the YH18 peptide in the fourth
      fas-1 domain of betaIG-H3 and function-blocking antibodies to integrins. RESULTS:
      Expression of betaIG-H3 was up-regulated in RA synovial tissue compared with
      synovial tissue from patients with osteoarthritis. FLS isolated from RA synovial
      tissue constitutively produced betaIG-H3, which was up-regulated by transforming
      growth factor beta1, interleukin-1beta, and tumor necrosis factor alpha. Although
      FLS expressed a variety of integrins, betaIG-H3 mediated adhesion and migration
      of FLS through interaction with alpha v beta3 integrin. Cytokines failed to
      affect the betaIG-H3-mediated adhesion. However, migration of FLS guided by
      betaIG-H3 was enhanced by interferon-gamma and platelet-derived growth factor
      type BB. The YH18 peptide in the fourth fas-1 domain of betaIG-H3 inhibited
      adhesion and migration in a dose-dependent manner. CONCLUSION: The results
      suggest that betaIG-H3, which is abundantly expressed in RA synovial tissue,
      plays a regulatory role in chronic destructive inflammation through the
      modulation of the adhesion and migration of FLS. This finding indicates the
      relevance of betaIG-H3 and alpha v beta3 integrin-interacting motifs as potential
      therapeutic targets in this disease.

PMID- 16947383
TI  - Differential tissue expression and activation of p38 MAPK alpha, beta, gamma, and
      delta isoforms in rheumatoid arthritis.
AB  - OBJECTIVE: Activation of p38 MAPK is a key signaling step in chronic
      inflammation. Inhibition of p38 MAPK is considered to be a promising future
      strategy to control inflammatory diseases, but studies of compounds to inhibit
      this kinase have so far been limited to investigation of their side effects. We
      undertook the present study to investigate which specific molecule, among 4
      different isoforms of p38 MAPK (alpha, beta, gamma, and delta), is predominantly
      expressed and activated in inflammation. Such knowledge could allow more specific
      targeting of p38 MAPK in inflammatory disease. METHODS: Studies were performed on
      inflamed tissue from patients with rheumatoid arthritis, as a prototype of
      inflammatory disease. The expression and activation of the alpha, beta, gamma,
      and delta isoforms of p38 MAPK were examined by immunoblotting,
      immunoprecipitation, and immunohistochemistry. RESULTS: Immunoblot analysis
      revealed that alpha and gamma were the predominantly expressed p38 MAPK isoforms,
      whereas the other 2 isoforms were less frequently present. By
      immunohistochemistry, the expression of all p38 MAPK isoforms was localized to
      the synovial lining layer as well as to blood vessels. Colabeling with cell
      specific markers revealed that macrophages expressed the alpha and gamma
      isoforms, synovial fibroblasts the beta and gamma isoforms, and granulocytes the
      delta isoform, whereas T lymphocytes were rarely positive for any p38 MAPK
      isoform. Double-labeling with isoform-specific antibody and pan-p38 antibody
      against the phosphorylated form of p38 MAPK showed activation of the alpha and
      gamma isoforms. Occasional activation of the beta isoform was also noted in the
      synovial lining and the endothelium, whereas the delta isoform, although
      expressed in pericytes around blood vessels, was not phosphorylated. This
      phosphorylation pattern was confirmed in immunoprecipitation studies in which
      activated p38 MAPK from synovial tissue extracts was identified as p38 MAPKalpha
      and -gamma but not p38 MAPKbeta or -delta. CONCLUSION: These data show that the
      alpha and gamma isoforms of p38 MAPK dominate in chronic inflammation. Effective
      strategies to inhibit p38 MAPK should therefore aim to specifically target either
      or both of these isoforms.

PMID- 16947384
TI  - Safety of the selective costimulation modulator abatacept in rheumatoid arthritis
      patients receiving background biologic and nonbiologic disease-modifying
      antirheumatic drugs: A one-year randomized, placebo-controlled study.
AB  - OBJECTIVE: To assess the safety of abatacept, a selective costimulation
      modulator, in patients with active rheumatoid arthritis (RA) who had been
      receiving > or =1 traditional nonbiologic and/or biologic disease-modifying
      antirheumatic drugs (DMARDs) approved for the treatment of RA for at least 3
      months prior to entry into the study. METHODS: This was a 1-year, multicenter,
      randomized, double-blind, placebo-controlled trial. Patients were randomized 2:1
      to receive abatacept at a fixed dose approximating 10 mg/kg by weight range, or
      placebo. RESULTS: The abatacept and placebo groups exhibited similar frequencies
      of adverse events (90% and 87%, respectively), serious adverse events (13% and
      12%, respectively), and discontinuations due to adverse events (5% and 4%,
      respectively). Five patients (0.5%) in the abatacept group and 4 patients (0.8%)
      in the placebo group died during the study. Serious infections were more frequent
      in the abatacept group than in the placebo group (2.9% versus 1.9%). Fewer than
      4% of patients in either group experienced a severe or very severe infection. The
      incidence of neoplasms was 3.5% in both groups. When evaluated according to
      background therapy, serious adverse events occurred more frequently in the
      subgroup receiving abatacept plus a biologic agent (22.3%) than in the other
      subgroups (11.7-12.5%). CONCLUSION: Abatacept in combination with synthetic
      DMARDs was well tolerated and improved physical function and physician- and
      patient-reported disease outcomes. However, abatacept in combination with
      biologic background therapies was associated with an increase in the rate of
      serious adverse events. Therefore, abatacept is not recommended for use in
      combination with biologic therapy.

PMID- 16947385
TI  - Immunohistologic analysis of zygapophyseal joints in patients with ankylosing
      spondylitis.
AB  - OBJECTIVE: Zygapophyseal joints of the spine are often affected in ankylosing
      spondylitis (AS). In this study, we undertook a systematic immunohistologic
      evaluation of the immunopathology of the zygapophyseal joints in patients with
      advanced AS. METHODS: We obtained zygapophyseal joints from 16 AS patients
      undergoing polysegmental correction of kyphosis and from 10 non-AS controls (at
      autopsy). Immunohistologic analysis of the bone marrow was performed by analyzing
      the number of infiltrating T cells (CD3, CD4, CD8), B cells (CD20), osteoclasts
      (CD68), bone marrow macrophages (CD68), and microvessel density (CD34) per high
      power field. RESULTS: Zygapophyseal joints from 6 of 16 AS patients, but from
      none of the controls, exhibited 2 or more CD3+ T cell aggregates, signifying
      persistent inflammation. Interstitial CD4+ and CD8+ T cells were significantly
      more frequent in AS patients compared with non-AS controls (P = 0.002 and P =
      0.049, respectively). While there was no clear difference between the number of
      CD20+ B cells in AS patients overall compared with controls, there was a
      significant difference when persistently inflamed joints from patients with AS
      were compared with joints without active inflammation from patients with AS or
      joints from controls (both P = 0.03). Microvessel density in bone marrow from AS
      patients with active inflammation was significantly higher than that in bone
      marrow from controls. CONCLUSION: This immunohistologic study of bone marrow from
      zygapophyseal joints demonstrates persistent inflammation in the spine of
      patients with AS, including those with longstanding disease. The findings of
      increased numbers of T cells and B cells and neoangiogenesis suggest that these
      features play a role in the pathogenesis of AS.

PMID- 16947396
TI  - Vascular amine oxidases are needed for leukocyte extravasation into inflamed
      joints in vivo.
AB  - OBJECTIVE: Leukocyte traffic from the blood to the joints is crucial in the
      pathogenesis of arthritis. A bifunctional endothelial cell-surface glycoprotein,
      AOC3 (amine oxidase, copper-containing 3; also known as vascular adhesion protein
      1), has both adhesive and enzymatic properties. We undertook this study to
      determine the contribution of AOC3 and its oxidase activity to leukocyte
      trafficking into inflamed joints in vivo. METHODS: We used gene-modified animals,
      molecular modeling, an AOC3 enzyme inhibitor, oxidase assays, and arthritis
      models (adjuvant-induced arthritis [AIA] in rats and anti-type II collagen
      antibody-induced arthritis in mice) to dissect the importance of AOC3 in vivo.
      RESULTS: The AOC3 inhibitor fitted well with a covalent binding mode into the
      active site of the AOC3 crystal structure. It selectively blocked the oxidase
      activity of AOC3 in enzyme assays. Intraperitoneal and oral administration of the
      AOC3 inhibitor significantly ameliorated rat AIA. In anti-type II collagen
      antibody-induced arthritis in mice, the AOC3 inhibitor also improved the outcome
      of the joint inflammation. The acute semicarbazide-sensitive amine oxidase
      blockade by the inhibitor had even more pronounced effects than genetic deletion
      of AOC3. Enzymatic analyses showed that the inhibitor also blocked 2 other
      structurally very closely related AOCs, but not any of more than 100 other
      enzymes tested. CONCLUSION: These are the first data to demonstrate that the
      enzymatic activity of the atypical endothelial adhesion molecule AOC3, and
      possibly that of other closely related ecto-oxidases, is crucial for leukocyte
      exit from the vessels in inflamed joints in vivo.

PMID- 16947397
TI  - Lymphocyte-independent connective tissue mast cells populate murine synovium.
AB  - OBJECTIVE: Mast cells (MCs) are a heterogeneous population of tissue-resident
      bone marrow-derived cells; distinct MC subpopulations are situated at specific
      microanatomic locations. The phenotype of the murine synovial MC remains
      undefined. Since MCs have been implicated in the pathogenesis of inflammatory
      arthritis, we sought to define the phenotype of the murine synovial MC population
      in normal and arthritic joints. We also examined the contribution of lymphocytes
      to synovial MC physiology. METHODS: The MC phenotype in healthy and K/BxN serum
      transfer-induced arthritic synovial tissue was defined using immunohistochemical
      staining of prototypic MC-specific proteases (murine MC proteases [mMCP] 1, 2, 4,
      5, 6, and 7) (chymases and tryptases). MC numbers and density were determined by
      histomorphometry in healthy and arthritic synovia. The lymphocyte contribution to
      MC populations was assessed using RAG-null mice. RESULTS: We found that synovial
      MCs display a connective tissue mast cell (CTMC) phenotype in both normal and
      arthritic synovial tissue, which expresses mMCP-4, -5, -6, and -7, but not mMCP-1
      or mMCP-2. In addition, MC hyperplasia was seen in the arthritic synovium. In RAG
      null mice, the phenotype and degree of MC hyperplasia were identical to those
      observed in normal mice with and without arthritis. Furthermore, in contrast to
      skin CTMCs, all synovial MCs expressed mMCP-6, demonstrating discrete differences
      between synovial CTMCs and other anatomic CTMC populations. CONCLUSION: Our
      findings demonstrate that the murine synovial MC population is composed of
      lymphocyte-independent CTMCs and identify arthritic synovium as a model system by
      which to gain insight into the poorly understood physiology of CTMCs in chronic
      inflammation.

PMID- 16947419
TI  - Soluble human p55 and p75 tumor necrosis factor receptors reverse spontaneous
      arthritis in transgenic mice expressing transmembrane tumor necrosis factor
      alpha.
AB  - OBJECTIVE: The roles of the transmembrane and secreted forms of tumor necrosis
      factor alpha (TNFalpha) in rheumatoid arthritis (RA) remain unclear. Agents used
      to inhibit TNFalpha have shown varying efficacy in RA patients, suggesting that
      anti-TNFalpha agents possess dissimilar mechanisms of action, including the
      ability to neutralize transmembrane (tmTNFalpha) and secreted TNFalpha. In this
      study, TNFalpha-knockout (TNFalpha-KO) mice that were genetically altered to
      express elevated levels of tmTNFalpha were constructed to further understand the
      roles of the 17-kd secreted, trimeric, and 26-kd transmembrane forms of TNFalpha.
      METHODS: A speed-congenic mating scheme was used to generate 3 unique strains of
      mice: 1) transgenic tmTgA86 mice overexpressing 26-kd tmTNFalpha and also
      secreting 17-kd trimeric TNFalpha (tmTNFalpha-transgenic), 2) TNFalpha-/- mice
      (TNFalpha-KO), and 3) transgenic mice overexpressing tmTNFalpha backcrossed to
      TNFalpha-KO mice (tmTNFalpha-transgenic/TNFalpha-KO). Mice were treated with
      phosphate buffered saline (as vehicle control), dexamethasone (as positive
      control), or modified recombinant human soluble TNF receptor (sTNFR) p55 or p75,
      and were assessed clinically and histopathologically for signs of inflammation
      and development of arthritis. RESULTS: The tmTNFalpha-transgenic/TNFalpha-KO mice
      were born with crinkled tails and spinal deformities similar to those in
      ankylosing spondylitis. By 2-4 weeks, these mice developed symmetric inflammatory
      arthritis, characterized by tissue swelling, pannus formation, and bone
      deformities. The tmTNFalpha-transgenic mice also developed spontaneous-onset
      arthritis, but at a slower rate (100% incidence by 10-12 weeks). Clinical and
      histologic progression of arthritis in the tmTNFalpha-transgenic/TNFalpha-KO mice
      was reduced by treatment with dexamethasone or with the p55 or p75 sTNFR (69% and
      63% reduction in total histologic score, respectively). CONCLUSION: These data
      show that arthritis is sufficiently initiated and maintained in tmTNFalpha
      transgenic/TNFalpha-KO mice, and that it can be neutralized by recombinant human
      p55 or p75 sTNFR, resulting in amelioration of the biologic and subsequent
      histologic destructive effects of tmTNFalpha.

PMID- 16947421
TI  - Early elevation in circulating levels of C-telopeptides of type II collagen
      predicts structural damage in articular cartilage in the rodent model of collagen
      induced arthritis.
AB  - OBJECTIVE: To investigate changes in the circulating levels of the C-telopeptide
      of type II collagen (CTX-II) with relation to disease onset and structural damage
      of cartilage in a rodent model of collagen-induced arthritis (CIA), and to
      investigate immunolocalization of the CTX-II epitope in the articular cartilage
      of affected joints. METHODS: Seven-week-old female Lewis rats were immunized with
      type II collagen and monitored using blood sampling at weekly intervals. At study
      termination (day 23), the animals were killed, synovial fluid was collected, and
      the affected joints were scored macroscopically for disease severity and
      underwent immunohistochemical evaluation. RESULTS: At the time of disease onset
      (day 15), which was characterized by redness and swelling of the affected joints
      (mean +/- SD macroscopic severity score 9.1 +/- 1.6), there was a 355% increase
      in serum CTX-II levels. The early change in serum CTX-II from day 0 to day 15
      showed a significant association with the severity of cartilage damage (r = 0.61,
      P < 0.01). Immunostaining revealed extensive presence of the CTX-II epitope in
      the damaged, uncalcified cartilage tissue. CONCLUSION: The elevation in serum CTX
      II concomitant with the onset of disease and proportional to cartilage damage
      demonstrates that CTX-II is a sensitive diagnostic tool for monitoring joint
      disease in the rodent model of CIA. Furthermore, the immunohistochemical findings
      are consistent with the concept that the major source of serum CTX-II is the
      damaged articular cartilage.

PMID- 16947423
TI  - Pathogenesis of osteoarthritis-like changes in the joints of mice deficient in
      type IX collagen.
AB  - OBJECTIVE: To examine the pathogenetic mechanisms of osteoarthritis (OA)-like
      changes in Col9a1-/- mice, which are deficient in type IX collagen. METHODS: Knee
      joints and temporomandibular joints (TMJs) from Col9a1-/- mice and their wild
      type (Col9a1+/+) littermates were examined by light microscopy.
      Immunohistochemical staining was performed to examine the expression of matrix
      metalloproteinase 3 (MMP-3) and MMP-13, degraded type II collagen, and the
      discoidin domain receptor 2 (DDR-2) in knee joints. Cartilage mechanics were also
      evaluated for compressive properties by microindentation testing of the tibial
      plateau and for tensile properties by osmotic loading of the femoral condyle.
      RESULTS: Histologic analysis showed age-dependent OA-like changes in the knee and
      TMJs of Col9a1-/- mice starting at the age of 3 months. At the age of 6 months,
      enhanced proteoglycan degradation was observed in the articular cartilage of the
      knee and TMJs of the mutant mice. The expression of MMP-13 and DDR-2 protein and
      the amount of degraded type II collagen were higher in the knee joints of Col9a1
      /- mice than in their wild-type littermates at the age of 6 months. Changes in
      cartilage mechanics were observed in the femoral and tibial plateaus of Col9a1-/-
      mice at 6 months, including a decrease in the compressive modulus and uniaxial
      modulus. At 3 and 6 months of age, tibial cartilage in Col9a1-/- mice was found
      to be more permeable to fluid flow, with an associated compromise in the fluid
      pressurization mechanism of load support. All of these changes occurred only at
      medial sites. CONCLUSION: Lack of type IX collagen in Col9a1-/- mice results in
      age-dependent OA-like changes in the knee joints and TMJs.

PMID- 16947426
TI  - Cloprostenol, a prostaglandin F(2alpha) analog, induces hypoxia in rat placenta:
      BOLD contrast MRI.
AB  - Blood oxygen level dependent (BOLD) contrast was used to monitor hypoxia induced
      by cloprostenol, a prostaglandin F(2alpha) (PGF(2alpha)) analog, in the rat
      embryo-placental unit (EPU). It is shown that administration of cloprostenol
      (0.025 mg/rat) at mid-gestation (day 16) reduced EPU oxygenation, as detected by
      BOLD contrast MRI, in correlation with induction of vascular endothelial growth
      factor (VEGF) gene (Vegfa) expression in the corresponding placenta (r = 0.56, p
      = 0.03). Elevated VEGF mRNA expression in response to cloprostenol treatment was
      also observed at early gestation (day 9) in the forming placenta (p = 0.04) and
      uterus (p = 0.03). Cloprostenol increased the expression levels of endothelin-1
      (ET-1) gene (Edn1) (p = 0.03) and its corresponding peptide (p = 0.02) in the
      forming placenta, as well as the expression of the endothelin receptor type A
      (ETA) gene (Ednra) in both the forming placenta (p = 0.009) and the uterus (p =
      0.01). The levels of the endothelin receptor type B (ETB) gene (Ednrb) were not
      affected in response to cloprostenol, but a significant elevation in the
      expression level of this receptor was observed in the uterus at mid- and late
      gestation (day 22) (p = 0.04 and 0.01 respectively), suggesting a role for ETB in
      the vasodilatory status of the pregnant uterus. It is suggested that PGF(2alpha)
      induces uteroplacental vasoconstriction in the rat, and that ET-1 may take part
      in mediating this effect, probably via activation of ETA receptor. The
      uteroplacental vasoconstriction induces hypoxia, as manifested by significant
      changes in BOLD MRI and by upregulation of VEGF.

PMID- 16947441
TI  - Proceedings of the 26th Annual Meeting of the International Society for Clinical
      Biostatistics. August 21-25, 2005. Szeged, Hungary.

PMID- 16947448
TI  - Walking barefoot decreases loading on the lower extremity joints in knee
      osteoarthritis.
AB  - OBJECTIVE: To evaluate the effects that modern shoes have on gait and lower
      extremity joint loads in osteoarthritis (OA). METHODS: Gait analyses were
      performed on 75 subjects with knee OA while they were wearing their everyday
      walking shoes and while they were walking barefoot. The trials involved
      optoelectronic detection of external markers during ambulation over a
      multicomponent force plate, and were matched for speed. Comparisons were made of
      gait parameters and joint loading during trials in which the subjects walked
      while wearing shoes and while barefoot. RESULTS: Peak joint loads at the hips and
      knees significantly decreased during barefoot walking, with an 11.9% reduction
      noted in the knee adduction moment. Stride, cadence, and range of motion at the
      lower extremity joints also changed significantly, but these changes could not
      explain the reduction in the peak joint loads. CONCLUSION: Shoes may
      detrimentally increase loads on the lower extremity joints. Once factors
      responsible for the differences in loads between with-shoe and barefoot walking
      are better delineated, modern shoes and walking practices may need to be
      reevaluated with regard to their effects on the prevalence and progression of OA
      in our society.

PMID- 16947528
TI  - Long-term comparison of rituximab treatment for refractory systemic lupus
      erythematosus and vasculitis: Remission, relapse, and re-treatment.
AB  - OBJECTIVE: Current treatments for systemic lupus erythematosus (SLE) and
      vasculitis contribute to mortality and incapacity and are only partially
      effective; thus, newer therapies are clearly needed. Depletion of B cells has led
      to disease control in patients with autoimmune disorders. We sought to assess the
      long-term efficacy and safety of a B cell-depleting therapy in patients with SLE
      and patients with vasculitis. METHODS: In a prospective study with a median
      followup of 24 months, 11 patients with active or refractory SLE and 11 patients
      with active or refractory antineutrophil cytoplasmic antibody-associated
      vasculitis (AAV) received a course of therapy with rituximab (an anti-CD20
      monoclonal antibody) along with a single dose of intravenous cyclophosphamide.
      RESULTS: Remission followed rapid B cell depletion, with response rates of 100%
      among the 11 patients with SLE (6 patients had a complete response, and 5
      patients had a partial response) and 91% among the 11 patients with AAV (9
      patients had a complete response, and 1 patient had partial remission). A renal
      response occurred in all 6 patients with lupus nephritis. Clinical improvement
      was accompanied by significant reductions in the daily dose of prednisolone.
      Relapse occurred in 64% of the patients with SLE and in 60% of those with AAV. B
      cell return preceded relapse in the majority of patients, and further treatment
      with rituximab proved effective. IgG and IgM levels were maintained in the normal
      range. The incidence of infective complications was low; however, infusion
      reactions were common, and human antichimeric antibodies developed in 5 of 14
      patients. CONCLUSION: B cell depletion offers the prospect of sustained disease
      remission and improved disease control combined with low toxicity in patients
      with active or refractory SLE or AAV. Relapse following treatment is common, but
      re-treatment is rapidly effective.

PMID- 16947529
TI  - Rapamycin reduces disease activity and normalizes T cell activation-induced
      calcium fluxing in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown
      origin. Current treatment options are often ineffective or poorly tolerated.
      Recent observations have revealed mitochondrial hyperpolarization and enhanced
      Ca2+ fluxing in T cells from SLE patients. Rapamycin, a lipophilic macrolide
      antibiotic that regulates mitochondrial transmembrane potential and Ca2+ fluxing,
      has been used safely and effectively to treat renal transplant rejection since
      1999. In addition, rapamycin has been shown to ameliorate T cell function and to
      prolong survival in lupus-prone MRL/lpr mice. We therefore undertook the present
      study to investigate whether rapamycin is beneficial in patients with SLE.
      METHODS: Nine patients with clinically active SLE that had been treated
      unsuccessfully with other immunosuppressive medications began therapy with
      rapamycin, 2 mg/day orally. Disease activity was assessed with the British Isles
      Lupus Assessment Group (BILAG) score, SLE Disease Activity Index (SLEDAI), and
      requirement for prednisone therapy. Mitochondrial transmembrane potential and
      Ca2+ fluxing were assessed by flow cytometry. RESULTS: In patients treated with
      rapamycin, the BILAG score was reduced by a mean +/- SEM of 1.93 +/- 0.9 (P =
      0.0218), the SLEDAI by 5.3 +/- 0.8 (P = 0.00002), and concurrent prednisone use
      by 26.4 +/- 6.7 mg/day (P = 0.0062) compared with pre-rapamycin treatment. While
      mitochondrial hyperpolarization persisted, pretreatment cytosolic and
      mitochondrial Ca2+ levels and T cell activation-induced rapid Ca2+ fluxing were
      normalized in rapamycin-treated patients. CONCLUSION: Rapamycin appears to be a
      safe and effective therapy for SLE that has been refractory to traditional
      medications. Mitochondrial dysfunction and Ca2+ fluxing could serve as biomarkers
      to guide decisions regarding future therapeutic interventions in SLE.

PMID- 16947531
TI  - Successful use of a humanized anti-interleukin-6 receptor antibody, tocilizumab,
      to treat amyloid A amyloidosis complicating juvenile idiopathic arthritis.
AB  - We report an excellent clinical response to treatment with a humanized anti
      interleukin-6 receptor antibody, tocilizumab, in a patient with progressive
      amyloid A (AA) amyloidosis complicating very active juvenile idiopathic
      arthritis. Treatment with tocilizumab immediately normalized the serum AA (SAA)
      level, and subsequently all of the clinical symptoms of AA amyloidosis
      disappeared. Serial gastrointestinal biopsy specimens showed marked lasting
      regression of AA protein deposits. The patient's functional ability score
      improved dramatically, she maintains her mobility, and she has regained her
      previous quality of life. Tocilizumab appears to have an excellent ability to
      suppress SAA levels and could therefore be an important therapeutic strategy in
      AA amyloidosis secondary to rheumatic diseases.

PMID- 16947625
TI  - Insulin-like growth factor binding protein 5 induces skin fibrosis: A novel
      murine model for dermal fibrosis.
AB  - OBJECTIVE: To determine the role of insulin-like growth factor binding protein 5
      (IGFBP-5) in the development of skin fibrosis in vivo, by examining the effect of
      overexpression of IGFBP-5 in mouse skin. METHODS: Wild-type C57BL/6J mice were
      injected subcutaneously with replication-deficient serotype 5 adenovirus
      expressing human IGFBP-3 (Ad3), IGFBP-5 (Ad5), or no complementary DNA (cAd).
      Mice were killed 3, 8, or 22 days postinjection. The dermal thickness and dermal
      collagen bundle thickness in skin sections were measured. The deposition of
      collagen in the extracellular matrix (ECM) was quantified using the Sircol assay.
      Expression of proliferating cell nuclear antigen (PCNA) and fibronectin, as
      determined by immunohistochemical analysis, was used to evaluate fibroblast
      activation, and vimentin and alpha-smooth muscle actin (alpha-SMA) were used to
      evaluate the fibroblast phenotype. RESULTS: Adenovirally expressed IGFBP was
      detected in dermal fibroblasts, endothelial cells, epithelial cells, and muscle
      bundles in Ad3- and Ad5-injected mice. Increased collagen deposition, denser
      dermal connective tissue, and increased collagen bundle thickness were observed
      in IGFBP-5-overexpressing mice. Dermal thickness and collagen bundle thickness
      were significantly increased in Ad5-injected mice compared with cAd- and Ad3
      injected mice. Treatment with Ad5 resulted in a dose-dependent increase in dermal
      and collagen bundle thickness. Increased deposition of collagen and fibronectin,
      increased numbers of PCNA-positive fibroblasts, as well as increased numbers of
      vimentin- and alpha-SMA-double-positive fibroblasts were detected in the dermis
      of IGFBP-5-overexpressing mouse skin. CONCLUSION: IGFBP-5 is a key mediator of
      fibrosis. IGFBP-5 mediates its profibrotic effects through fibroblast activation,
      increased ECM deposition, and myofibroblastic transformation of dermal
      fibroblasts. Overexpression of IGFBP-5 provides a novel model for studying the
      pathogenesis of skin fibrosis in systemic sclerosis.

PMID- 16947627
TI  - Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor
      therapy: Results of a multicenter, randomized, double-blind, placebo-controlled,
      phase III trial evaluating primary efficacy and safety at twenty-four weeks.
AB  - OBJECTIVE: To determine the efficacy and safety of treatment with rituximab plus
      methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an
      inadequate response to anti-tumor necrosis factor (anti-TNF) therapies and to
      explore the pharmacokinetics and pharmacodynamics of rituximab in this
      population. METHODS: We evaluated primary efficacy and safety at 24 weeks in
      patients enrolled in the Randomized Evaluation of Long-Term Efficacy of Rituximab
      in RA (REFLEX) Trial, a 2-year, multicenter, randomized, double-blind, placebo
      controlled, phase III study of rituximab therapy. Patients with active RA and an
      inadequate response to 1 or more anti-TNF agents were randomized to receive
      intravenous rituximab (1 course, consisting of 2 infusions of 1,000 mg each) or
      placebo, both with background MTX. The primary efficacy end point was a response
      on the American College of Rheumatology 20% improvement criteria (ACR20) at 24
      weeks. Secondary end points were responses on the ACR50 and ACR70 improvement
      criteria, the Disease Activity Score in 28 joints, and the European League
      against Rheumatism (EULAR) response criteria at 24 weeks. Additional end points
      included scores on the Functional Assessment of Chronic Illness Therapy-Fatigue
      (FACIT-F), Health Assessment Questionnaire (HAQ) Disability Index (DI), and Short
      Form 36 (SF-36) instruments, as well as Genant-modified Sharp radiographic scores
      at 24 weeks. RESULTS: Patients assigned to placebo (n = 209) and rituximab (n =
      311) had active, longstanding RA. At week 24, significantly more (P < 0.0001)
      rituximab-treated patients than placebo-treated patients demonstrated ACR20 (51%
      versus 18%), ACR50 (27% versus 5%), and ACR70 (12% versus 1%) responses and
      moderate-to-good EULAR responses (65% versus 22%). All ACR response parameters
      were significantly improved in rituximab-treated patients, who also had
      clinically meaningful improvements in fatigue, disability, and health-related
      quality of life (demonstrated by FACIT-F, HAQ DI, and SF-36 scores, respectively)
      and showed a trend toward less progression in radiographic end points. Rituximab
      depleted peripheral CD20+ B cells, but the mean immunoglobulin levels (IgG, IgM,
      and IgA) remained within normal ranges. Most adverse events occurred with the
      first rituximab infusion and were of mild-to-moderate severity. The rate of
      serious infections was 5.2 per 100 patient-years in the rituximab group and 3.7
      per 100 patient-years in the placebo group. CONCLUSION: At 24 weeks, a single
      course of rituximab with concomitant MTX therapy provided significant and
      clinically meaningful improvements in disease activity in patients with active,
      longstanding RA who had an inadequate response to 1 or more anti-TNF therapies.

PMID- 16947629
TI  - Association of increased interferon-inducible gene expression with disease
      activity and lupus nephritis in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To study 5 type I interferon (IFN)-inducible genes (LY6E, OAS1, OASL,
      MX1, and ISG15) in patients with systemic lupus erythematosus (SLE) and to
      correlate expression levels with disease activity and/or clinical manifestations.
      METHODS: Peripheral blood cells were obtained from 48 SLE patients, 48 normal
      controls, and 22 rheumatic disease controls, and total RNA was extracted and
      reverse transcribed into complementary DNA. Gene expression levels were measured
      by real-time polymerase chain reaction, standardized to a housekeeping gene, and
      summed to an IFN score. Disease activity was determined by the Safety of
      Estrogens in Lupus Erythematosus: National Assessment-Systemic Lupus
      Erythematosus Disease Activity Index (SELENA-SLEDAI) composite. RESULTS: Each
      gene was highly expressed in SLE patients compared with normal controls (P < or =
      0.0003) or disease controls (P < or = 0.0008 except for MX1). IFN scores were
      positively associated with the SELENA-SLEDAI instrument score (P = 0.001), the
      SELENA-SLEDAI flare score (P = 0.03), and the physician's global assessment score
      (P = 0.005). Compared with patients without nephritis, lupus nephritis patients
      had higher IFN scores (overall P < 0.0001), especially during active renal
      disease. IFN scores were weakly associated with neurologic manifestations.
      Elevated IFN scores were positively associated with the current presence of anti
      double-stranded DNA (anti-dsDNA) antibodies (P = 0.007) or hypocomplementemia (P
      = 0.007). LY6E expression levels distinguished active from inactive lupus
      nephritis (P = 0.02) and were positively associated with proteinuria (P = 0.009).
      CONCLUSION: The 5 IFN-inducible genes were highly expressed in SLE patients, and
      increased levels were correlated with disease activity defined by several
      methods. IFN scores, or LY6E levels, were elevated in lupus nephritis patients,
      especially during active renal disease, and in patients with anti-dsDNA antibody
      positivity and hypocomplementemia. IFN scores, or LY6E levels, may be useful as a
      biomarker for lupus nephritis therapy.

PMID- 16947632
TI  - The prevalence and incidence of biopsy-proven lupus nephritis in the UK: Evidence
      of an ethnic gradient.
AB  - OBJECTIVE: Renal involvement is a major complication of systemic lupus
      erythematosus (SLE) and is a strong determinant of morbidity and mortality. There
      have been no previous studies of the epidemiology of lupus nephritis. Our aim was
      to establish the prevalence and incidence of biopsy-proven lupus nephritis in the
      northwest of England in 2001 and to examine the influence of age, sex, and
      ethnicity. METHODS: Adults (age 18 years and older) with biopsy-proven lupus
      nephritis were identified from 5 sources: renal biopsy databases,
      dialysis/transplant databases, nephrologists' patients, clinic lists, and lupus
      patient groups. The denominator data for the northwest of England were
      ascertained from the 2001 census. RESULTS: We identified 208 cases of biopsy
      proven lupus nephritis (176 women, 32 men): the overall prevalence was 4.4 per
      100,000 population (95% confidence interval [95% CI] 3.8-5.0), 7.1 per 100,000
      (95% CI 6.1-8.2) in women, and 1.4 per 100,000 (95% CI 1.0-2.0) in men. The
      prevalence was significantly higher among women in the ethnic subgroups: 110.3
      per 100,000 population (95% CI 55.0-197.3) in Chinese patients, 99.2 per 100,000
      (95% CI 55.5-163.6) in Afro-Caribbean, 21.4 per 100,000 (95% CI 12.0-35.2) in
      Indo-Asian (Asians from the Indian subcontinent), and 5.6 per 100,000 (95% CI 4.7
      6.7) in white patients. The overall annual incidence rate was 0.40 per 100,000
      population per year (95% CI 0.24-0.63), with a rate of 0.68 (95% CI 0.40-1.10) in
      women and 0.09 (95% CI 0.01-0.32) in men. Capture-recapture methods did not
      suggest any additional cases. CONCLUSION: This first estimate of the prevalence
      and incidence of biopsy-proven lupus nephritis demonstrates dramatic differences
      in prevalence according to ethnicity, with an increasing gradient from the white
      to the Indo-Asian, Afro-Caribbean, and Chinese populations.

PMID- 16947634
TI  - A proposal for a pediatric version of the Systemic Lupus International
      Collaborating Clinics/American College of Rheumatology Damage Index based on the
      analysis of 1,015 patients with juvenile-onset systemic lupus erythematosus.
AB  - OBJECTIVE: To devise a modified version of the Systemic Lupus International
      Collaborating Clinics/American College of Rheumatology Damage Index (SDI) for use
      in children and adolescents with systemic lupus erythematosus (SLE), based on the
      frequency and distribution of damage in patients with juvenile-onset SLE and the
      sources of damage that are most suitable for inclusion in a pediatric damage
      index. METHODS: In this cross-sectional study, damage was assessed through the
      SDI. Clinical assessments included evaluation of growth failure and delayed
      puberty, which were believed to be important sources of damage that are not
      incorporated in the SDI but should be included in a pediatric version of the
      instrument. RESULTS: A total of 1,015 patients with juvenile-onset SLE in 39
      countries were enrolled in the study. Of these, 405 patients (39.9%) had an SDI
      score of > or =1 (mean +/- SD score 0.8 +/- 1.4). Renal damage (13%),
      neuropsychiatric damage (10.7%), and musculoskeletal damage (10.7%) were observed
      most frequently, followed by ocular damage (8.2%) and skin damage (7.6%). Growth
      failure and delayed puberty were recorded in 15.3% and 11.3% of patients,
      respectively. A pediatric version of the SDI was devised, with inclusion of
      growth failure and delayed puberty as new domains. CONCLUSION: We propose a
      modified version of the SDI for use in patients with juvenile-onset SLE. This new
      instrument warrants prospective validation in other populations of patients seen
      in different clinical or research settings.

PMID- 16947635
TI  - Increased levels of transforming growth factor beta receptor type I and up
      regulation of matrix gene program: A model of scleroderma.
AB  - OBJECTIVE: Previously published studies have demonstrated that a majority of
      systemic sclerosis (SSc) fibroblasts exhibit elevated levels of transforming
      growth factor beta type I receptor (TGFbetaRI). An experimental model that
      recapitulates this condition was established in control dermal fibroblasts by
      titrating the dose of adenovirus vector expressing TGFbetaRI (AdTGFbetaRI). The
      present study was undertaken to determine the functional consequences of
      increased levels of TGFbetaRI in SSc. METHODS: Gene array analysis of control
      dermal fibroblasts transduced with AdTGFbetaRI was performed using GeneChip
      expression arrays. Gene validation was done by Northern blot, quantitative
      reverse transcriptase-polymerase chain reaction, and Western blot techniques.
      TGFbeta blockade was performed using soluble TGFbeta receptor. TGFbetaRI
      kinase/activin receptor-like kinase 5 was inhibited with pharmacologic
      inhibitors. TGFbetaRI and TGFbetaRII protein levels and collagen production were
      examined by Western blotting in primary dermal fibroblasts from 9 SSc patients
      and 9 healthy adults. Endogenous TGFbetaRI levels were suppressed in control and
      SSc fibroblasts using specific small interfering RNA (siRNA). RESULTS: Global
      gene analysis indicated that a 2-fold increase in TGFbetaRI levels in control
      fibroblasts resulted in profibrotic changes that closely resembled the phenotype
      of SSc fibroblasts. A total of 125 genes were up-regulated, including COL1A1,
      COL1A2, and connective tissue growth factor, and 206 genes were down-regulated.
      Elevated production of collagen in cells transduced with AdTGFbetaRI was
      dependent on the autocrine TGFbeta, but not TGFbetaRI kinase activity. Eight of
      the 9 SSc strains exhibited increased levels of TGFbetaRI protein, which
      correlated with increased collagen synthesis. Treatment of SSc and matched
      control fibroblasts with siRNA that normalizes TGFbetaRI levels reverted collagen
      protein production in SSc fibroblasts to the levels observed in control
      fibroblasts. CONCLUSION: Our findings demonstrate that aberrantly expressed
      TGFbetaRI may drive an autocrine loop involved in the up-regulation of collagen
      and other matrix-related genes in SSc fibroblasts.

PMID- 16947639
TI  - Effect of diffusion in inhomogeneous magnetic fields on balanced steady-state
      free precession.
AB  - In this work, the effects of susceptibility variation from dilute, micron-sized
      spherical field perturbers and diffusion on balanced steady-state free precession
      (bSSFP) are analyzed. Predictions from Monte Carlo simulations are in good
      agreement with experiments and reveal that, for diffusing protons, susceptibility
      variation becomes apparent as a reduction in the overall bSSFP signal intensity.
      This reduction depends on microsphere parameters (radius and susceptibility
      difference), as well as on sequence-related parameters (repetition time and flip
      angle) and on relaxation times. Specific Monte Carlo results from one set of
      parameter values can be extrapolated to another set of values by means of a
      scaling law and a substitution model. The scaling law, derived from the Bloch
      Torrey equation, captures the dependencies of bSSFP signal reduction on
      susceptibility and diffusion-related changes and on repetition time, whereas the
      substitution model describes those on flip angle and relaxation times.

PMID- 16947772
TI  - Streptococcus bovis: causal or incidental involvement in cancer of the colon?

PMID- 16947773
TI  - Function of interleukin-20 as a proinflammatory molecule in rheumatoid and
      experimental arthritis.
AB  - OBJECTIVE: The pathogenesis of rheumatoid arthritis (RA) reflects an ongoing
      imbalance between proinflammatory and antiinflammatory cytokines. Interleukin-20
      (IL-20) has proinflammatory properties for keratinocytes. In this study, we
      sought to determine whether IL-20 is involved in RA. METHODS: We analyzed IL-20
      levels in synovial fluid from RA patients. IL-20 and its receptors were detected
      in RA synovial fibroblasts (RASFs), using immunohistochemical staining. The
      effect of IL-20 on endothelial cells, neutrophils, and RASFs was investigated
      using MTT and migration assays. The expression of IL-20 and its receptors in
      healthy rats and in rats with collagen-induced arthritis (CIA) was also analyzed.
      Soluble IL-20 receptor type I (sIL-20RI) or sIL-20RII was administered to rats
      with CIA by intramuscular electroporation, and the severity of arthritis was
      monitored. RESULTS: RA patients expressed significantly higher levels of synovial
      fluid IL-20 than did the rheumatic disease controls. IL-20 and its receptors were
      expressed in the synovial membranes and RASFs. IL-20 induced RASFs to secrete
      monocyte chemoattractant protein 1, IL-6, and IL-8, and it promoted neutrophil
      chemotaxis, RASF migration, and endothelial cell proliferation. Both IL-20 and IL
      20RI were up-regulated in the rat CIA model. In vivo, electroporated sIL-20RI
      plasmid DNA decreased the severity of arthritis in the rats with CIA. CONCLUSION:
      IL-20 was up-regulated in the synovial fluid of RA patients and acted as a
      chemokine that attracted the migration of neutrophils and RASFs in vitro. The rat
      CIA model demonstrated that IL-20 was involved in the pathogenesis of arthritis,
      because sIL-20RI significantly reduced arthritis in rats with CIA. Thus, IL-20
      may modulate the incidence and severity of arthritis and play important roles at
      local sites of inflammation.

PMID- 16947774
TI  - Tumor necrosis factor alpha antagonist use and cancer in patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: Concerns persist about a possible association between tumor necrosis
      factor alpha (TNFalpha) antagonist treatment and development of cancers in
      patients with rheumatoid arthritis (RA). This study was undertaken to estimate
      the association between treatment with biologic disease-modifying antirheumatic
      drugs (DMARDs) and development of cancer in patients with RA. METHODS: We
      conducted a cohort study pooling administrative databases from 2 US states and 1
      Canadian province. A cohort of patients who had received a diagnosis of RA on >
      or =1 occasion and had been prescribed DMARDs was identified. We categorized
      patients with a prescription for a biologic DMARD as biologic DMARD users, and
      those with a prescription for methotrexate (MTX) but no biologic DMARD as MTX
      users. We used time-varying propensity scores to adjust for the large number of
      possible confounders and stratified proportional hazards regression to estimate
      the effects of biologic DMARDs on cancer. The primary end points were hematologic
      malignancies (lymphoma, multiple myeloma, and leukemia) and common solid tumors
      (colorectal, lung, stomach, breast, prostate, uterine, ovarian, urinary
      tract/bladder, and melanoma). RESULTS: The pooled cohort included 1,152 biologic
      DMARD users and 7,306 MTX users. We identified 11 hematologic malignancies and 46
      solid tumors during 2,940 person-years of biologic DMARD use, and 88 hematologic
      malignancies and 558 solid tumors during 30,300 person-years of MTX use.
      Comparing biologic DMARD users with MTX users, the propensity score-adjusted
      pooled hazard ratio was 1.37 (95% confidence interval 0.71-2.65) for hematologic
      malignancies and 0.91 (95% confidence interval 0.65-1.26) for solid tumors.
      CONCLUSION: Our results indicate that users of biologic agents are unlikely to
      have a substantial increase in the risk of hematologic malignancies and solid
      tumors as compared with MTX users. Despite the use of large combined data sets,
      studying the effect of an infrequent exposure (biologic DMARDs) on rare diseases
      (hematologic malignancies) remains a challenge.

PMID- 16947775
TI  - Endothelin axis polymorphisms in patients with scleroderma.
AB  - OBJECTIVE: To evaluate the distribution of polymorphisms in the endothelin 1
      (EDN1), endothelin receptor A (EDNRA) and endothelin receptor B (EDNRB) genes in
      systemic sclerosis (SSc; scleroderma) and SSc subsets. METHODS: Two hundred five
      patients with SSc and 255 healthy controls were screened for polymorphisms in
      EDN1, EDNRA, and EDNRB, using sequence-specific primer-polymerase chain reaction.
      The polymorphisms studied were at the following positions: for EDN1, -1370 (T
      1370G) of the promoter, +138 of exon 1 (+138 A/-), +85 of exon 3 (E106E), and +23
      of exon 5 (K198N); for EDNRA, -231 of exon 1 (G-231A), and +69(H323H) and +105
      (E335E) of exon 6; for EDNRB, +2841 of exon 2 (EDNRB-3), -2547 of exon 3 (EDNRB
      2), and -2446 of exon 3 (EDNRB-1). RESULTS: No significant differences between
      the SSc group as a whole and control subjects were observed for any of the
      investigated polymorphisms in EDN1, EDNRA, and EDNRB. However, compared with
      patients with limited cutaneous SSc, patients with diffuse skin involvement had
      an increased frequency of allele carriage of EDNRB-1A (76.8% versus 54.4%; P =
      0.002), EDNRB-2A (79.7% versus 60.2%; P = 0.006), and EDNRB-3G (79.7% versus
      56.6%; P = 0.001). Significantly increased carriage frequencies for EDNRA alleles
      H323H/C and E335E/A were observed in SSc patients with anti-RNA polymerase (anti
      RNAP) antibodies, compared with both anti-RNAP-negative SSc patients (P < 0.05)
      and control subjects (P < 0.005). CONCLUSION: The finding of associations between
      endothelin receptors A and B and distinct clinical and immunologic SSc subsets
      supports the role of endothelin and its receptors in the pathogenesis of SSc.
      However, these findings and their functional significance need to be confirmed
      and investigated in future studies.

PMID- 16947776
TI  - Clinical differences between idiopathic and scleroderma-related pulmonary
      hypertension.
AB  - OBJECTIVE: Pulmonary arterial hypertension related to scleroderma (PAH-Scl) is
      associated with high morbidity and mortality as well as poorer response to
      therapy and worse outcomes compared with the idiopathic form of PAH (IPAH).
      Scleroderma is an autoimmune disease that can affect left and right heart
      function directly through inflammation and fibrosis and indirectly through
      systemic and pulmonary hypertension. This study tested the hypothesis that an
      increased prevalence of left heart disease might explain the higher mortality in
      patients with PAH-Scl compared with patients with IPAH. METHODS: The study was
      designed as a retrospective cohort study comparing the baseline clinical data
      from 91 consecutive patients (41 with IPAH and 50 with PAH-Scl). Cox proportional
      hazards models were used to predict the effect of clinical covariates on patient
      survival. RESULTS: Patients with PAH-Scl had a lower mean pulmonary artery
      pressure (46.6 mm Hg versus 54.4 mm Hg in patients with IPAH; P = 0.002) despite
      similar levels of cardiac dysfunction (cardiac index 2.2 and 2.1
      liters/minute/m(2), respectively; P = 0.19). Echocardiography revealed similar
      degrees of right ventricular dysfunction in the 2 groups, whereas a predominance
      of left heart dysfunction was observed in patients with PAH-Scl. One- and three
      year survival estimates were 87.8% and 48.9%, respectively, in patients with PAH
      Scl and 95.1% and 83.6%, respectively, in those with IPAH. Patients with PAH-Scl
      were 3.06 times more likely to die than were patients with IPAH, after
      controlling for the presence of pericardial effusion; there was no significant
      change in increased risk of death in PAH-Scl after controlling for left heart
      disease. CONCLUSION: The results confirm that there are significant clinical and
      survival differences between IPAH and PAH-Scl. The presence of left heart
      disease, although more common in PAH-Scl, was not predictive of the higher
      mortality in these patients.

PMID- 16947777
TI  - Medial collateral ligament healing in macrophage metalloelastase (MMP-12)
      deficient mice.
AB  - Medial collateral ligament (MCL) injuries heal by a wound repair scar response
      controlled by a complex cellular and cytokine environment. Many enzymes
      participate in wound repair, particularly the matrix metalloproteinases. We
      hypothesize macrophage metalloelastase (MME/MMP-12) deficiency results in
      impaired healing of MCL injury. One hundred fifty MME-deficient and 150 WT
      (MME+/+) mice underwent knee MCL transection with the opposite knee as a sham
      operated control. Mice were sacrificed at 3, 7, 28, 42, and 56 days. At each of
      the five time points, 15 mice were utilized for biological and 15 were utilized
      for biomechanical testing. Outcome measures were the presence of macrophages to
      represent the inflammatory phase of wound healing, collagen synthesis to assay
      for matrix repair, and biomechanical testing for repair strength.
      Immunohistochemistry demonstrated significantly fewer macrophages in cut MCLs
      from MME-deficient mice versus wild-type (WT) mice at 3, 7, 28, and 42 days (all
      p<or=0.04). In situ hybridization to Col1a1 mRNA in the MME-deficient cut MCLs at
      7, 28, and 42 day time points showed a decreased level of type I pro-collagen
      mRNA compared to the WT cut MCLs (p<0.05). Biomechanical testing revealed cut
      ligaments from MME-deficient mice had significantly lower ultimate force and
      stiffness compared to cut ligaments from WT mice (p<0.001), with maximal
      differences of 40% at 7 days for ultimate force and 28 days for stiffness (p<0.05
      by Tukey post hoc test). We conclude MME is important in the multifactorial
      cascade of knee MCL injury healing, showing significant differences in both the
      early inflammatory and in the matrix tissue synthesis phases.

PMID- 16947779
TI  - Insulin resistance and impaired beta cell function in rheumatoid arthritis.
AB  - OBJECTIVE: To identify factors that regulate glucose metabolism in rheumatoid
      arthritis (RA). METHODS: We evaluated the homeostatic model assessment of insulin
      resistance (HOMA-IR) and beta cell function (HOMA-B) in 94 RA patients. We
      investigated the relationship between characteristics known to affect glucose
      metabolism in the general population (age, abdominal obesity [waist
      circumference], hypertension, antihypertensive therapy) as well as
      characteristics of RA (disease activity, glucocorticoid therapy) and insulin
      resistance and beta cell function. RESULTS: Patients with high-grade inflammation
      (high-sensitivity C-reactive protein value >1.92 mg/liter) (n = 81) were more
      insulin resistant than patients with low-grade inflammation (n = 13), whereas
      beta cell function was similar in both groups. Insulin resistance and beta cell
      function were similar in both groups after adjustment for waist circumference.
      All recorded characteristics except for age were associated with HOMA-IR or/and
      HOMA-B in univariate analyses. In mixed regression models, abdominal obesity and
      patient's assessment of disease activity (by visual analog scale) were predictors
      of insulin resistance. The Disease Activity Score assessed using 28-joint counts
      for swelling and tenderness, tender joint count, and patient's assessment of
      disease activity were associated with reduced beta cell function, and the
      cumulative dose of glucocorticoids was associated with enhanced beta cell
      function. The cumulative glucocorticoid dose in all study patients was a mean of
      only 536 mg (95% confidence interval 239-1,173). In patients with high-grade
      inflammation, age was further associated with impaired beta cell function,
      whereas use of angiotensin-converting enzyme inhibitors or angiotensin II type 1
      receptor blockers was associated with enhanced beta cell function. CONCLUSION:
      The modifiable factors of abdominal obesity, antihypertensive therapy, disease
      activity, and use of glucocorticoids appear to affect glucose metabolism in RA.

PMID- 16947780
TI  - Association of HLA-C3 and smoking with vasculitis in patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: To compare HLA-C genotypes and smoking habits in patients with
      vasculitis or other severe extraarticular manifestations of rheumatoid arthritis
      (ExRA) with those in RA patients without extraarticular disease. METHODS:
      Patients were recruited from a large research database of patients with RA at the
      Mayo Clinic, from 2 Swedish cohorts of prevalent RA cases, and from a regional
      Swedish early RA cohort. Patients with severe ExRA (n = 159) and control patients
      with RA but no history of ExRA (non-ExRA controls) (n = 178) were matched for
      duration of RA and for clinical center. Data on smoking at RA onset, rheumatoid
      factor (RF) status, and antinuclear antibodies (ANAs) were extracted from the
      medical records. Polymerase chain reaction-based HLA-C genotyping was performed
      using a sequence-specific primer kit. RESULTS: The distribution of HLA-C alleles
      was significantly different between patients with RA-associated vasculitis and
      non-ExRA controls (P = 0.014). This was mainly due to a positive association of
      the HLA-C3 allele with vasculitis (allele frequency 0.411 in vasculitis patients
      versus 0.199 in non-ExRA controls; P < 0.001) and a decreased frequency of HLA-C7
      (0.122 and 0.243, respectively; P = 0.018). The association between HLA-C3 and
      vasculitis was not due to linkage disequilibrium with HLA-DRB1. Smoking (P =
      0.001), RF positivity (P < 0.0001), and presence of ANAs (P < 0.0001) were all
      associated with ExRA. HLA-C3 and smoking were both significant predictors of
      vasculitis in a multivariate model. CONCLUSION: Vasculitis in RA is associated
      with HLA-C3. Smoking is an independent predictor of vasculitis and other types of
      severe ExRA. Our results suggest that these variables are among the genetic and
      environmental factors that contribute significantly to the pathomechanisms of
      systemic RA.

PMID- 16947781
TI  - Measuring function in rheumatoid arthritis: Identifying reversible and
      irreversible components.
AB  - OBJECTIVE: Measurement of physical function at one point in time cannot
      distinguish impairment caused by the active disease process from chronic
      irreversible impairment. We aimed to dissect these two components of functional
      limitation in rheumatoid arthritis (RA) by using the disability index of the
      Health Assessment Questionnaire (HAQ) as the measure of function. METHODS: We
      performed a secondary analysis of data from 6 contemporary clinical trials of RA
      (2,763 patients). Patients in whom remission was achieved in the trials, based on
      a simplified disease activity index, were identified. In an individual patient,
      HAQ scores at trial entry represented both reversible and irreversible
      impairments, while HAQ scores at the time of RA remission represented the mostly
      irreversible component, and the difference between these corresponded to the
      component related to disease activity. We tested the concept that the HAQ has a
      reversible and an irreversible component by associating the HAQ score during
      remission with 2 measures associated with the degree of accrued damage: duration
      of RA and radiographic severity. RESULTS: Among patients in whom clinical
      remission was achieved (n = 295), average HAQ scores despite clinical remission
      increased progressively with the duration of RA, from 0.19 (<2 years of RA) to
      0.36 (2-<5 years) to 0.38 (5-<10 years) to 0.55 (>/=10 years) (P < 0.001). The
      reversibility of HAQ scores decreased with the duration of RA (median 100%,
      83.3%, 81.9%, and 66.7%, respectively; P < 0.001). Findings were similar in
      patients subgrouped by quartile of radiographic scores. CONCLUSION: Differences
      in the sources of functional limitations should be considered in the
      interpretation of functional measures, and in their use for prediction and in
      cost analyses.

PMID- 16947782
TI  - Double-blind randomized controlled clinical trial of the interleukin-6 receptor
      antagonist, tocilizumab, in European patients with rheumatoid arthritis who had
      an incomplete response to methotrexate.
AB  - OBJECTIVE: To establish the safety and efficacy of repeat infusions of
      tocilizumab (previously known as MRA), a humanized anti-interleukin-6 (IL-6)
      receptor antibody, alone and in combination with methotrexate (MTX), for the
      treatment of rheumatoid arthritis (RA). METHODS: The study group comprised 359
      patients with active RA in whom the response to MTX was inadequate. During a
      stabilization period, these patients received their current dose of MTX for at
      least 4 weeks. Following stabilization, they were randomized to 1 of 7 treatment
      arms, as follows: tocilizumab at doses of 2 mg/kg, 4 mg/kg, or 8 mg/kg either as
      monotherapy or in combination with MTX, or MTX plus placebo. RESULTS: A 20%
      response (improvement) according to the American College of Rheumatology criteria
      (ACR20 response) was achieved by 61% and 63% of patients receiving 4 mg/kg and 8
      mg/kg of tocilizumab as monotherapy, respectively, and by 63% and 74% of patients
      receiving those doses of tocilizumab plus MTX, respectively, compared with 41% of
      patients receiving placebo plus MTX. Statistically significant ACR50 and ACR70
      responses were observed in patients receiving combination therapy with either 4
      mg/kg or 8 mg/kg of tocilizumab plus MTX (P < 0.05). A dose-related reduction in
      the Disease Activity Score in 28 joints was observed from week 4 onward, in all
      patients except those receiving monotherapy with 2 mg/kg of tocilizumab. In the
      majority of patients who received 8 mg/kg of tocilizumab, the C-reactive protein
      level/erythrocyte sedimentation rate normalized, while placebo plus MTX had
      little effect on these laboratory parameters. Tocilizumab was mostly well
      tolerated, with a safety profile similar to that of other biologic and
      immunosuppressive therapies. Alanine transaminase and aspartate transaminase
      levels followed a sawtooth pattern (rising and falling between infusions). There
      were moderate but reversible increases in the nonfasting total cholesterol and
      triglyceride levels and reversible reductions in the high-density lipoprotein
      cholesterol and neutrophil levels. There were 2 cases of sepsis, both of which
      occurred in patients who were receiving combination therapy with 8 mg/kg of
      tocilizumab plus MTX. CONCLUSION: These results indicate that targeted blockade
      of IL-6 signaling is a highly efficacious and promising means of decreasing
      disease activity in RA.

PMID- 16947783
TI  - Relationship between genetic variants in the adenosine pathway and outcome of
      methotrexate treatment in patients with recent-onset rheumatoid arthritis.
AB  - OBJECTIVE: Among patients with rheumatoid arthritis (RA), there is a high degree
      of interindividual variability in the degree of response to methotrexate (MTX)
      treatment. This study was undertaken to explore polymorphisms in genes
      contributing to antiinflammatory adenosine release as novel predictors of MTX
      treatment outcome. METHODS: In 205 patients with newly diagnosed RA, 5
      polymorphisms in 5 genes coding for enzymes related to the release of adenosine
      were analyzed. All patients received standardized MTX treatment (up to 25 mg per
      week orally), combined with folic acid. MTX efficacy was evaluated by the Disease
      Activity Score (DAS) and compared among genotypes. The association between MTX
      related adverse events and genotype was also assessed. The following
      polymorphisms were determined: AMPD1 34C>T, ATIC 347C>G, ITPA 94C>A, MTR 2756A>G,
      and MTRR 66A>G. When significant differences were found by chi-square analysis,
      odds ratios (ORs) and 95% confidence intervals were calculated. RESULTS: Patients
      carrying the AMPD1 34T allele, ATIC 347CC, or ITPA 94CC were more likely to have
      a good clinical response, as defined by a DAS of < or =2.4 (OR [95% confidence
      interval] 2.1 [1.0-4.5], 2.5 [1.3-4.7], and 2.7 [1.1-8.1], respectively). The
      likelihood of a good clinical response was increased if patients possessed all 3
      favorable genotypes (OR 27.8 [95% confidence interval 3.2-250]). Regarding
      toxicity, only ATIC G allele carriers experienced a greater frequency of adverse
      events (OR 2.0 [95% confidence interval 1.1-3.7]). CONCLUSION: Polymorphisms in
      the AMPD1, ATIC, and ITPA genes are associated with good clinical response to MTX
      treatment. These findings indicate that genotyping may help in the identification
      of patients who will benefit most from MTX treatment and may assist clinicians in
      making treatment decisions regarding patients with recent-onset RA.

PMID- 16947863
TI  - Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): xeroderma
      pigmentosum without and with Cockayne syndrome.
AB  - Defects in the xeroderma pigmentosum type B (XPB) gene (ERCC3), a DNA helicase
      involved in nucleotide excision repair (NER) and an essential subunit of the
      basal transcription factor, TFIIH, have been described in only three families. We
      report three new XPB families: one has two sisters with relatively mild xeroderma
      pigmentosum (XP) symptoms not previously associated with XPB mutations and two
      have severe XP/Cockayne syndrome (CS) complex symptoms. All XP-B cells had
      reduced NER and post-ultraviolet (UV) cell viability. Surprisingly, cells from
      the milder XP sisters had the same missense mutation (c.296T>C, p.F99S) that was
      previously reported in two mild XP/CS complex brothers. These cells had higher
      levels of XPB protein than the severely affected XP/CS complex patients. An XPB
      expression vector with the p.F99S mutation partially complemented the NER defect
      in XP-B cells. The three severely affected XP/CS complex families all have the
      same splice acceptor site mutation (c.2218-6C>A, p.Q739insX42) in one allele.
      This resulted in alteration of 41 amino acids at the C terminus, producing
      partial NER complementation. This limited number of mutations probably reflects
      the very restricted range of alterations of this vital protein that are
      compatible with life. We found new mutations in the second allele yielding
      markedly truncated proteins in all five XP or XP/CS complex families: c.1273C>T,
      p.R425X; c.471+1G>A, p.K157insTSDSX; c.807-808delTT, p.F270X; c.1421-1422insA,
      p.D474EfsX475; and c.1633C>T, p.Q545X. The remarkable phenotypic heterogeneity of
      XPB is associated with partially active missense mutations in milder patients
      while severe XP/CS complex patients have nonsense mutations in both alleles with
      low levels of altered XPB proteins.

PMID- 16947907
TI  - Retroviral vector production using suspension-adapted 293GPG cells in a 3L
      acoustic filter-based perfusion bioreactor.
AB  - Recombinant retroviruses are now an established tool for gene delivery. Presently
      they are mainly produced using adherent cells. However, due to the restrictive
      nature of adherent cell culture, this mode of production is hampered by low cell
      specific productivity and small production units. The large-scale production of
      retroviral vectors could benefit from the adaptation of retrovirus packaging cell
      lines to suspension culture. Here, we describe the ability of a 293 packaging
      cell line to produce retroviral vectors in suspension culture at high titer.
      Adherent 293GPG cells, producing a Moloney Murine Leukemia Virus (MoMLV)
      retrovirus vector pseudotyped with the vesicular stomatitis virus G (VSVG)
      envelope protein and expressing a TK-GFP fusion protein, were adapted to
      suspension culture in calcium-free DMEM. At a cell density similar to adherent
      cell culture, the suspension culture produced retroviral vector consistently in
      the range of 1 x 10(7) infectious viral particles/mL (IVP/mL), with a specific
      productivity threefold higher than adherent culture. Furthermore, at the same
      medium replacement frequency, the suspension producer cells could be cultured at
      higher density than their adherent counterparts, which resulted in virus titer of
      3-4 x 10(7) IVP/mL at 11.0 x 10(6) cells/mL. This corresponds to a 10-fold
      increase in viral concentration compared to adherent cells. The capacity to up
      scale the retroviral vector production was also demonstrated by performing a 2
      VVD perfusion culture for 9 days in a 3L Chemap bioreactor. The combination of
      suspension and perfusion led to a 20-fold increase in maximum virus productivity
      compared to the adherent culture.

PMID- 16947910
TI  - A three-year follow-up of major depression, dysthymia, minor depression and
      subsyndromal depression: results from a population-based study.
AB  - This study examined the 3-year outcome of major depression (MD)/dysthymic
      disorder (DD), minor depression (MinD), and subsyndromal symptomatic depression
      (SSD) in a population-based sample. The aims were to study the fluctuating nature
      of the symptoms of depression and to analyze the risk of fulfilling the criteria
      for MD/DD at the follow-up. An extensive questionnaire was sent out to persons
      ages 20-64 years registered in Stockholm County. Depression was assessed with the
      Major Depression Inventory. After 3 years the procedure was repeated, and 8,622
      persons participated in both waves. Diagnoses of MD/DD, MinD, or SSD were made.
      Highest 3-year stability in fulfilling the criteria for a specific depressive
      category was found in MD/DD, and of those affected, only 35.9% had one or fewer
      symptoms of depression at the 3-year follow-up. The frequency of those with one
      or fewer symptom of depression was equal in MinD (58.9%) and in SSD (56.5%). The
      relative risk (RR) of fulfilling the criteria for MD/DD at Wave 2 was highest for
      those affected by MD/DD (RR=22.4) at Wave 1, whereas those fulfilling the
      criteria for MinD or SSD had similar rates (RR=4.8 and 5.0, respectively). This
      study supports the view that depression is a dimensional illness, with the
      affected persons moving in and out of diagnostic subtypes. The 3-year prognosis
      was severe in half of the affected persons in all three diagnostic depression
      categories.

PMID- 16947924
TI  - Bayesian statistics in medicine: a 25 year review.
AB  - This review examines the state of Bayesian thinking as Statistics in Medicine was
      launched in 1982, reflecting particularly on its applicability and uses in
      medical research. It then looks at each subsequent five-year epoch, with a focus
      on papers appearing in Statistics in Medicine, putting these in the context of
      major developments in Bayesian thinking and computation with reference to
      important books, landmark meetings and seminal papers. It charts the growth of
      Bayesian statistics as it is applied to medicine and makes predictions for the
      future. From sparse beginnings, where Bayesian statistics was barely mentioned,
      Bayesian statistics has now permeated all the major areas of medical statistics,
      including clinical trials, epidemiology, meta-analyses and evidence synthesis,
      spatial modelling, longitudinal modelling, survival modelling, molecular genetics
      and decision-making in respect of new technologies.

PMID- 16947981
TI  - Evidence for adaptive selection acting on the tRNA and rRNA genes of human
      mitochondrial DNA.
AB  - In order to identify putative adaptive human mitochondrial DNA (mtDNA), transfer
      RNA (tRNA), and ribosomal RNA (rRNA) variants, we assembled a sequential
      mutational tree from 2,460 human mtDNA coding sequences, thus providing the
      relative age of all mtDNA sequence variants. Deleterious mutations affect
      evolutionarily conserved nucleotides and have been eliminated from the older
      internal branches of the tree by purifying selection, while beneficial mutations
      also alter conserved nucleotides but have been enriched in the internal branches
      of the tree by adaptive selection. Neutral polymorphisms alter poorly conserved
      nucleotides and are distributed throughout the tree. Stem nucleotides are more
      constrained than loop nucleotides. The functional importance of both types of
      nucleotide variants was assessed by comparison to the average evolutionary
      conservation index (CI) of all known pathogenic tRNA mutations, thus permitting
      discrimination between internal branch neutral and adaptive tRNA variants. This
      revealed that 19% of the stem and 13% of the loop internal branch tRNA variants
      were potentially adaptive. Since few pathogenic rRNA mutations are known,
      evidence for adaptive rRNA variation was revealed by higher stem to loop variant
      ratios and elevated CIs in the internal branches vs. external branches. Moreover,
      variants among stem noncanonical apposition bases predominantly created new
      Watson-Crick (WC) base pairs, thus also suggesting adaptive selection. Among the
      putative adaptive tRNA and rRNA polymorphisms, a number were found to occur at
      the base of the branches of the tree, to have recurred multiple times, and to be
      associated with altered human phenotypes. Therefore, a significant portion of
      ancient tRNA and rRNA polymorphisms appear to have been adaptive, and these are
      affecting human health today.

PMID- 16948054
TI  - Leukocyte migration to rheumatoid joints: Enzymes take over.

PMID- 16948055
TI  - A comparative analysis of bleomycin-induced incomplete chromosome elements in two
      mammalian cell lines using a telomeric PNA probe.
AB  - Fluorescence in situ hybridization (FISH) with a telomeric peptide nucleic acid
      probe was employed to analyze the induction of incomplete chromosome elements
      (ICE; i.e., incomplete chromosomes and terminal fragments) by bleomycin (BLM) in
      two mammalian cell lines. Chinese hamster embryo cells (CHE cell line, average 2n
      = 23) and domestic rabbit cells (CPC cell line, average 2n = 44) were treated
      with 2.5 micro g/ml BLM; after 18 hr of incubation, first-division metaphases
      were stained with the telomeric probe, and ICE and other unstable chromosomal
      aberrations were scored. BLM induced ICE, dicentrics, and interstitial acentric
      fragments in CHE cells, but only ICE in CPC cells. About 50% of the metaphases in
      BLM-treated CHE cells contained one or more pairs of ICE, while only 20% of
      treated CPC cells contained ICE. Almost 100% of the BLM-induced ICE in both cell
      lines consisted of pairs formed by an incomplete chromosome and a terminal
      fragment. Our results confirm that ICE are the most frequent type of unstable
      chromosomal aberration induced by BLM in mammalian cells. Moreover, the present
      study shows that an increase in the chromosome number does not necessarily result
      in an increase in the frequency of BLM-induced ICE. The results also show that
      the difference in the chromosomal sensitivity to BLM in CHE and CPC cells is due
      to differences in the absolute frequency but not in the pattern (i.e., type and
      proportion) of ICE.

PMID- 16948056
TI  - Screening and characterization of variant Theta-class glutathione transferases
      catalyzing the activation of ethylene dibromide to a mutagen.
AB  - Ethylene dibromide (EDB) is a widespread environmental pollutant and
      mutagen/carcinogen. Certain Theta-class glutathione transferases (GSTs), enzymes
      that catalyze the reaction of reduced glutathione (GSH) with electrophiles,
      activate EDB to a mutagen. Previous studies have shown that human GST T1-1, but
      not rat GST T2-2, activates EDB. We have constructed an E. coli lacZ reversion
      mutagenicity assay system in which expression of recombinant GST supports
      activation of EDB to a mutagen. Hexa-histidine N-terminal tagging of GST T1-1
      results in greatly enhanced expression of the recombinant enzyme and gives a lacZ
      strain that shows a mutagenic response to EDB at extremely low levels
      (approximately 1 ng EDB per plate). The hexa-histidine-tagged enzyme was purified
      in one step by Ni(2+)-affinity chromatography. We applied the lacZ mutagenicity
      assay to the rapid screening of a library of variant GST Theta enzymes. Sequence
      variants with altered catalytic activities were identified, purified, and
      characterized.

PMID- 16948057
TI  - Protection from radiation-induced mitochondrial and genomic DNA damage by an
      extract of Hippophae rhamnoides.
AB  - Hippophae rhamnoides or seabuckthorn is used extensively in Indian and Tibetan
      traditional medicine for the treatment of circulatory disorders, ischemic heart
      disease, hepatic injury, and neoplasia. In the present study, we have evaluated
      the radioprotective potential of REC-1001, a fraction isolated from the berries
      of H. rhamnoides. Chemical analysis of the extract indicated that REC-1001 was
      approximately 68% by weight polyphenols, and contained kaempferol, isorhamnetin,
      and quercetin. The effect of REC-1001 on modulating radiation-induced DNA damage
      was determined in murine thymocytes by measuring nonspecific nuclear DNA damage
      at the whole genome level using the alkaline halo assay and by measuring
      sequence/gene-specific DNA damage both in nuclear DNA (beta-globin gene) and in
      mitochondrial DNA using a quantitative polymerase chain reaction. Treatment with
      10 Gy resulted in a significant amount of DNA damage in the halo assay and
      reductions in the amplification of both the beta-globin gene and mitochondrial
      DNA. REC-1001 dose-dependently reduced the amount of damage detected in each
      assay, with the maximum protective effects observed at the highest REC-1001 dose
      evaluated (250 micro g/ml). Studies measuring the nicking of naked plasmid DNA
      further established the radioprotective effect of REC-1001. To elucidate possible
      mechanisms of action, the antioxidant properties and the free-radical scavenging
      activities of REC-1001 were evaluated. REC-1001 dose-dependently scavenged
      radiation-induced hydroxyl radicals, chemically-generated superoxide anions,
      stabilized DPPH radicals, and reduced Fe(3+) to Fe(2+). The results of the study
      indicate that the REC-1001 extract of H. rhamnoides protects mitochondrial and
      genomic DNA from radiation-induced damage. The polyphenols/flavonoids present in
      the extract might be responsible for the free radical scavenging and DNA
      protection afforded by REC-1001.

PMID- 16948114
TI  - An account of the discrepancy between MRI and PET cerebral blood flow measures. A
      high-field MRI investigation.
AB  - There is controversy concerning the discrepancy between absolute cerebral blood
      flow (CBF) values measured using positron emission tomography (PET) and magnetic
      resonance imaging (MRI). To gain insight into this problem, the increased signal
      to-noise ratio (SNR) and extended T(1) relaxation times of blood and tissue at
      3.0 T were exploited to perform pulsed arterial spin labeling (PASL) MRI
      measurements as a function of spatial resolution and post-labeling delay. The
      results indicate that, when using post-labeling delays shorter than 1500 ms, MRI
      gray matter flow values may become as high as several times the correct CBF
      values owing to tissue signal contamination by remaining arterial blood water
      label. For delays above 1500 ms, regional PASL-based CBF values (n = 5; frontal
      gray matter: 48.8 +/- 3.3(SD) ml/100 g/min; occipital gray matter: 49.3 +/- 4.5
      ml/100 g/min) comparable with PET-based measurements can be obtained by using
      spatial resolutions comparable with PET (5-7.5 mm in-plane). At very high
      resolution (2.5 x 2.5 x 3 mm(3)), gray matter CBF values were found to increase
      by 10-20%, a consequence attributed to reduction in partial volume effects with
      cerebrospinal fluid and white matter. The recent availability of MRI field
      strengths of 3.0 T and higher will facilitate the use of MRI-based CBF
      measurements in the clinic.

PMID- 16948115
TI  - IgG and IgM anticardiolipin antibodies following treatment with infliximab plus
      methotrexate in patients with early rheumatoid arthritis.
AB  - OBJECTIVE: To assess the occurrence of anticardiolipin antibodies (aCL) in
      patients with early rheumatoid arthritis (RA) receiving treatment with infliximab
      plus methotrexate (MTX) versus MTX alone. METHODS: The first 299 patients
      enrolled in the randomized, Active-Controlled Study of Patients Receiving
      Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset (ASPIRE)
      trial who had baseline (week 0) samples available for aCL testing were included
      in this study. Sera were collected at weeks 0, 30, and 54 from 110 patients
      taking infliximab 3 mg/kg plus MTX, 98 patients taking infliximab 6 mg/kg plus
      MTX, and 91 patients taking placebo plus MTX. IgG and IgM aCL were measured using
      an anticardiolipin assay. RESULTS: IgG and IgM aCL positivity at baseline was
      similar in all treatment groups. Most patients were negative for IgG aCL at
      baseline and remained so at the last followup evaluation. One percent (2 of 208)
      of patients who received infliximab plus MTX and were negative for IgG aCL at
      baseline were positive for IgG aCL at weeks 30 and 54. A slightly higher
      proportion of patients who received infliximab plus MTX and were negative for IgM
      aCL at baseline were positive for IgM aCL at weeks 30 and 54 (4.8% [10 of 208])
      as compared with patients who received placebo plus MTX (1.1% [1 of 91]), but the
      difference was not significant. CONCLUSION: There was a low incidence of the
      development of aCL in patients with early RA who received infliximab in
      combination with MTX, and the difference was not significant compared with
      patients who received placebo plus MTX.

PMID- 16948116
TI  - Increase in production of matrix metalloproteinase 13 by human articular
      chondrocytes due to stimulation with S100A4: Role of the receptor for advanced
      glycation end products.
AB  - OBJECTIVE: S100 proteins have been implicated in various inflammatory conditions,
      including arthritis. The aims of this study were to determine whether
      chondrocytes produce S100A4 and whether S100A4 can stimulate the production of
      matrix metalloproteinase 13 (MMP-13) by articular chondrocytes via receptor for
      advanced glycation end products (RAGE)-mediated signaling. METHODS: The
      expression of chondrocyte S100A4 was analyzed by immunohistochemistry using
      normal and osteoarthritic (OA) cartilage and by immunoblotting of chondrocyte
      cell lysates. RAGE signaling was examined by stimulating chondrocytes with S100A4
      and monitoring for the activation of MAP kinases and NF-kappaB. Production of MMP
      13 was determined in the conditioned medium. A pulldown assay using biotin
      labeled S100A4 was used to demonstrate binding to RAGE. RESULTS: S100A4
      expression was detected in human articular chondrocytes by immunoblotting and
      appeared to increase in the cell lysates from OA tissue. Marked positive
      immunostaining for S100A4 was also noted in sections of human cartilage with
      changes due to OA. Stimulation of chondrocytes with S100A4 increased the
      phosphorylation of Pyk-2, MAP kinases, and activated NF-kappaB, followed by
      increased production of MMP-13 in the conditioned medium. This signaling was
      inhibited in cells pretreated with soluble RAGE, advanced glycation end product
      bovine serum albumin, or the antioxidant Mn(III)tetrakis (4-benzoic acid)
      porphyrin, or by overexpression of a dominant-negative RAGE construct. A pulldown
      assay showed that S100A4 binds to RAGE in chondrocytes. CONCLUSION: This is the
      first study to demonstrate that S100A4 binds to RAGE and stimulates a RAGE
      mediated signaling cascade, leading to increased production of MMP-13. Since both
      S100A4 and RAGE are up-regulated in OA cartilage, this signaling pathway could
      contribute to cartilage degradation in OA.

PMID- 16948117
TI  - Identification of fibronectin neoepitopes present in human osteoarthritic
      cartilage.
AB  - OBJECTIVE: Fibronectin fragments are present at high concentrations in the
      cartilage of patients with rheumatoid arthritis and patients with osteoarthritis
      (OA) and have been shown to promote cartilage catabolism in human cartilage
      cultures, suggesting that fibronectin fragments participate in the initiation and
      progression of arthritic disease. This study was undertaken to 1) identify the
      major fibronectin fragments in human OA cartilage and confirm their ability to
      elicit cartilage catabolism, 2) identify the cleavage sites in fibronectin and
      generate the corresponding neoepitope antibodies, and 3) explore the utility of
      fibronectin neoepitopes as biomarkers. METHODS: Fibronectin fragments were
      purified from human OA cartilage using affinity chromatography; their N-termini
      were then identified by sequencing. Bovine nasal cartilage was treated with
      affinity-purified fibronectin fragments and assayed for aggrecan breakdown by
      monitoring the release of glycosaminoglycans and the aggrecan neoepitope
      1771AGEG. Fibronectin neoepitopes were detected by Western blotting in cytokine
      treated media of human cartilage explants, and by immunohistochemical analyses of
      human OA cartilage. RESULTS: Multiple fibronectin fragments were isolated from
      human OA cartilage, and all contained the N-terminus 272VYQP. These fragments
      induced aggrecanase-mediated cartilage catabolism in bovine cartilage explants.
      Fibronectin fragments with the N-terminus 272VYQP and fragments with the C
      terminus VRAA271 were detected following cytokine treatment of human cartilage
      extracts. These neoepitopes localized with areas of aggrecan loss in OA
      cartilage. CONCLUSION: Human OA cartilage contains fibronectin fragments with
      catabolic activity and a major cleavage site within fibronectin. This study is
      the first to characterize fibronectin neoepitopes in OA cartilage, suggesting
      that they may represent a novel biomarker of arthritis.

PMID- 16948118
TI  - Unzipping the cuticle of the human hair shaft to obtain micron/nano keratin
      filaments.
AB  - An attempt has been made to obtain intact individual keratin filaments of various
      levels from micron cortical, micron macrofibril to nano intermediate filament and
      polypeptide alpha-helix from the human hair shaft. The feasibility of this
      initiative has been largely demonstrated by finding that there is a longitudinal
      seam/zipper on the cuticle of the human hair shaft, which can be unzipped by
      certain solvents such as performic acid and urea, allowing one to use an
      anatomical approach to separate intact individual micron/nano filaments. Micron
      cortical and macrofibril filaments have been obtained. It is also found that the
      cortical filaments are twisted together to form a yarn, giving rise to the
      strength for the hair shaft; and that individual cortical filaments are often 2-2
      paired in a similar structure to the double helix.

PMID- 16948119
TI  - Optical spectroscopic elucidation of beta-turns in disulfide bridged cyclic
      tetrapeptides.
AB  - Vibrational circular dichroism (VCD) spectroscopic features of type II beta-turns
      were characterized previously, but, criteria for differentiation between beta
      turn types had not been established yet. Model tetrapeptides, cyclized through a
      disulfide bridge, were designed on the basis of previous experimental results and
      the observed incidence of amino acid residues in the i + 1 and i + 2 positions in
      beta-turns, to determine the features of VCD spectra of type I and II beta-turns.
      The results were correlated with electronic circular dichroism (ECD) spectra and
      VCD spectra calculated from conformational data obtained by molecular dynamics
      (MD) simulations. All cyclic tetrapeptides yielded VCD signals with a higher
      frequency negative and a lower frequency positive couplet with negative lobes
      overlapping. MD simulations confirmed the conformational homogeneity of these
      peptides in solution. Comparison with ECD spectroscopy, MD, and quantum chemical
      calculation results suggested that the low frequency component of VCD spectra
      originating from the tertiary amide vibrations could be used to distinguish
      between types of beta-turn structures. On the basis of this observation, VCD
      spectroscopic features of type II and VIII beta-turns and ECD spectroscopic
      properties of a type VIII beta-turn were suggested. The need for independent
      experimental as well as theoretical investigations to obtain decisive
      conformational information was recognized.

PMID- 16948120
TI  - Evidence for a strong selenium-aromatic interaction derived from crystallographic
      data and ab initio quantum chemical calculations.
AB  - Increasing attention is being paid to the role of selenium, both as an essential
      component required for the activity of many enzymes and in the context of
      selenium-based pharmaceutical agents. A wide range of therapeutics that include
      selenium are on the market and under development, such as antihypertensive,
      anticancerogenic, antiviral, and immunosuppressive agents. Computer-aided drug
      design (CADD) has proven to be an important tool for the development of new
      drugs. Many CADD techniques, including docking, molecular dynamics simulation,
      and other receptor-based approaches, require an accurate understanding of the
      nature of the intermolecular forces that act to stabilize protein-ligand
      complexes; moreover, a quantitative assessment of these interactions furthers our
      efforts to rationalize the drug design process. In this paper, we consider one
      class of interaction involving selenium, that between Se and aromatic rings.
      Prior work has shown that interactions between divalent sulfur and aromatic rings
      are observed much more frequently than would be expected on the basis of chance,
      both in protein structures and the crystal structures of organic compounds that
      include these moieties. Recent studies on the optimization of inhibitor-protein
      binding also suggest that sulfur-aromatic interactions are important in
      stabilizing these complexes and may be crucial focal point for CADD. Given that
      selenium and sulfur have similar chemistry, and that selenium is significantly
      more polarizable, we propose that Se-aromatic interactions may also play an
      important stabilizing role in the structure of folded proteins and in drug
      protein complexes. We have tested this hypothesis against data from the Cambridge
      Crystallographic Database and ab initio quantum chemical calculations. We have
      found evidence that selenium does interact strongly with aromatic rings and may
      play a role analogous to sulfur in stabilizing protein folds. In addition,
      selenium should be considered along with sulfur in rational drug design
      strategies that seek to improve binding to target protein sites that include
      aromatic rings.

PMID- 16948121
TI  - Interaction of synthetic peptides corresponding to the scaffolding domain of
      Caveolin-3 with model membranes.
AB  - Caveolin-1 and -3 are among the few proteins in which the functional domains are
      contiguous and modular. The interaction of synthetic peptides spanning the
      scaffolding domain of caveolin-3 with model membranes has been investigated. The
      peptides include the scaffolding domain, the aromatic and positively charged
      residues at the C-terminal end of this domain as well as deletion of three amino
      acids TFT, observed in certain patients with limb girdle muscular dystrophy. All
      of the peptides appear to be peripherally bound to the bilayer surface. However,
      no preferential binding to sphingomyelin and cholesterol-containing lipid
      vesicles was observed. Deletion of TFT appears to affect the association with
      lipid vesicles compared with the native sequence. Association with lipids
      decreases considerably when TFT as well as the aromatic-rich segment YWFYR, which
      occurs at the extreme C-terminus of the scaffolding domain, are deleted.

PMID- 16948122
TI  - P48 is a predictive marker for outcome of postoperative interferon-alpha
      treatment in patients with hepatitis B virus infection-related hepatocellular
      carcinoma.
AB  - BACKGROUND: Postoperative interferon-alpha (IFN-alpha) therapy improved survival
      in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).
      The identification of predictive markers of outcome will help to select patients
      who are most likely to benefit from treatment. METHODS: An immunohistochemical
      study of P48 was performed on specimens that were collected from patients in a
      randomized trial who received postoperative IFN-alpha therapy (Group 1; n = 80
      patients) and who did not receive postoperative IFN-alpha therapy (Group 2; n =
      75 patients). Positive P48 expression was graded as >/=20% positive cells in 1
      sample. RESULTS: Eighty-one patients were positive for P48, and 74 patients were
      negative for P48. The clinicopathologic data were comparable between patients
      with P48-negative and P48-positive staining. Disease-free survival (DFS) and
      overall survival (OS) in P48-positive patients were better than that in P48
      negative patients in Group 1 (DFS, P = .036; OS, P = .014), however, DFS and OS
      did not differ between patients with positive and negative P48 in Group 2. OS in
      P48-positive patients from Group 1 was better than that in patients with P48
      positive patients from Group 2 (OS, P = .001) but did not differ when P48 was
      negative. In Group 1, the risk factors for DFS were cirrhosis and P48 staining,
      and the risk factors for OS were tumor differentiation and P48 staining. Receiver
      operating curve analysis indicated that, in the first 2 years of DFS, combined
      cirrhosis and P48 had good predictive accuracy; and, in the first 4 years of OS,
      combined tumor differentiation and P48 had good predictive accuracy. CONCLUSIONS:
      P48 was useful as a predictive marker of outcome after postoperative IFN-alpha
      treatment in patients with HBV-related HCC.

PMID- 16948123
TI  - Novel approaches in the treatment of systemic mastocytosis.
AB  - In the absence of curative options, therapy for aggressive forms of systemic
      mastocytosis (SM) has relied in the use of cytoreductive agents, mainly
      interferon-alpha (IFN-alpha) and cladribine. However, responses are transient and
      only occur in a subset of patients. Gain-of-function mutations at codon 816 of
      the KIT protooncogene lead to constitutively active Kit receptor molecules, which
      are central to the pathogenesis of SM. Recent advances in the understanding of
      the molecular underpinnings of SM have led to the development of small molecules
      targeting mutant Kit tyrosine kinase isoforms that significantly have widened the
      range of therapeutic options for patients with SM. Some of these promising
      agents, such as dasatinib, AMN107, and PKC412, currently are under investigation
      in clinical trials whereas, others are at different stages of preclinical
      development. In addition, monoclonal antibodies directed to neoplastic mast cell
      restricted surface antigens constitute a viable option for the treatment of SM
      that warrants further investigation.

PMID- 16948124
TI  - Noninvasive imaging for evaluation of the systemic delivery of capsid-modified
      adenoviruses in an orthotopic model of advanced lung cancer.
AB  - BACKGROUND: Variable expression of the coxsackie and adenovirus receptor (CAR)
      has limited gene transfer efficacy to many types of tumors. Consequently, tropism
      modified adenoviruses have been developed for enhanced infectivity. To the
      authors' knowledge, targeting approaches for nonsmall cell lung cancer (NSCLC)
      have not been comprehensively evaluated. The current hypothesis was that modified
      adenoviruses could be used for increasing gene transfer to and killing of NSCLC
      cells in vitro and in vivo. METHODS: Ten NSCLC cell lines were analyzed to
      represent the different NSCLC histologies. Because clinical tumors may differ
      from established cell lines, 6 clinical specimens fresh from patients were
      analyzed. For in vivo studies, a novel orthotopic murine model of advanced lung
      cancer was developed. Because tumor response is difficult to quantitate in
      orthotopic models, noninvasive imaging of green fluorescent protein (GFP) was
      utilized as a surrogate for tumor size measurements. RESULTS: Adenoviruses whose
      capsids were modified with RGD-4C, the serotype 3 knob, or polylysine displayed
      increased gene transfer to NSCLC cell lines and clinical samples in comparison to
      serotype 5 viruses. Conditionally replicating oncolytic adenoviruses (CRAds) with
      the same modifications showed enhanced therapeutic efficiency in vitro and in
      vivo. The median survival of mice treated with Ad5.pK7-Delta24 or Ad5-Delta24RGD
      increased 37% (P<.01). GFP imaging allowed noninvasive individualized detection
      of response and recurrence. CONCLUSIONS: Targeting of adenovirus to heterologous
      receptors can improve killing of NSCLC cells. Utilization of clinical samples and
      an orthotopic model of advanced lung cancer may provide clinically relevant
      translational data.

PMID- 16948125
TI  - Correlation of cytotechnologists' parameters with their performance in rapid
      prescreening of papanicolaou smears.
AB  - BACKGROUND: Efficient quality control is essential to ensure high sensitivity of
      Papanicolaou (Pap) smears. For this purpose, rescreening of 10% random negative
      smears is increasingly felt to be ineffective. Rapid rescreening (RR) of all
      negative Pap smears is more practical and has received widespread acceptance,
      especially in Europe, although its sensitivity is difficult to monitor and its
      retrospective nature may influence the vigilance of the screeners. The method of
      rapid prescreening (RPS) overcomes these drawbacks because rapid review of Pap
      smears precedes full screening. METHODS: All routine conventional Pap smears (n =
      8364) over 2 months underwent RPS by 12 cytotechnologists, followed by full
      screening. Data were analyzed to determine correlation between the RPS
      sensitivity of individual cytotechnologists and both their sensitivity in full
      screening and their years of experience as cytotechnologists. RESULTS: There was
      a striking variability in sensitivity (15.4%-72.7%) among the 12 screeners with
      an atypical squamous cells of undetermined significance (ASCUS) threshold. There
      was no correlation between RPS sensitivity of individual cytotechnologists with
      either their sensitivity in full screening or their years of experience as
      cytotechnologists. CONCLUSIONS: The skills required of a cytotechnologist for
      achieving a high sensitivity in RPS are apparently different from those of full
      screening and are independent of the sensitivity of the screeners at full
      screening or of the years of experience as cytotechnologists.

PMID- 16948126
TI  - Rituximab combined with cladribine or with cladribine and cyclophosphamide in
      heavily pretreated patients with indolent lymphoproliferative disorders and
      mantle cell lymphoma.
AB  - BACKGROUND: In vitro studies have shown synergistic or additive interactions
      between rituximab and purine nucleoside analogues. The results of recent clinical
      trials seem to confirm these preclinical observations. METHODS: For the current
      study, the authors evaluated the feasibility, efficacy, and toxicity of combined
      regimens that consisted of either rituximab plus cladribine (2-CdA) (the RC
      regimen) or RC plus cyclophosphamide (the RCC regimen) in the treatment of
      patients with heavily pretreated, indolent lymphoid malignancies. Fifty-four
      adult patients with recurrent or refractory, low-grade non-Hodgkin lymphoma (LG
      NHL) and B-cell chronic lymphocytic leukemia (B-CLL) were treated according to
      the RC/RCC regimens. The RC protocol consisted of intravenous rituximab at a dose
      of 375 mg/m(2) on Day 1 and 2-CdA at a dose of .12 mg/kg per day on Days 2
      through 6. The RCC protocol consisted of rituximab at a dose of 375 mg/m(2) on
      Day 1, 2-CdA at a dose of 0.12 mg/m(2) on Days 2 through 4, and intravenous
      cyclophosphamide at a dose of 250 mg/m(2) per day on Days 2 to 4. The RC/RCC
      courses were repeated at 4-week intervals. RESULTS: Thirty-three patients with B
      CLL, 12 patients with LG-NHL and 9 patients with mantle cell lymphoma (MCL)
      entered the study. Thirty-three patients (61%) had recurrent disease after prior
      therapy, and 21 patients (39%) had refractory disease. Thirty-one patients were
      treated on the RC regimen, and 23 patients were treated on the RCC regimen. Six
      patients (11%) achieved a complete response, and 33 patients (60%) achieved a
      partial response. The median failure-free survival of responders was 10.5 months.
      The treatment revealed tolerability, with episodes of severe neutropenia (Grade 3
      and 4 [according to World Health Organization criteria]) observed in 6 patients
      (11%), episodes of Grade 3 and 4 infections observed in 11 patients (20%), and
      episodes of Grade 3-4 thrombocytopenia observed in 4 patients (7%). CONCLUSIONS:
      The RC and RCC regimens were highly effective and well tolerated modalities of
      treatment in heavily pretreated patients with indolent lymphoproliferative
      disorders.

PMID- 16948127
TI  - Applicability of the Bethesda System 2001 to a public health setting.
AB  - BACKGROUND: The degree of applicability of the Bethesda System 2001 (TBS 2001)
      for cervicovaginal cytology to a public health setting is unknown, and
      extrapolations from available data are unwarranted. METHODS: A "before/after"
      study design was used to evaluate the impact of TBS 2001 on an organized,
      population-based screening program in northern Italy. Between 2003-2004, 6
      cytology laboratories converted from TBS 1991 to TBS 2001. A set of screening
      indicators based on TBS 2001 (85,012 patients) were compared with those based on
      TBS 1991 (199,833 patients) by means of their laboratory- and patient age
      standardized ratio with a 95% confidence interval (CI). RESULTS: The prevalence
      of cervical intraepithelial neoplasm (CIN)2-3/carcinoma was stable between the 2
      populations. TBS 2001 had no effect on the unsatisfactory rate (1.99% vs. 2.03%
      for TBS 1991) nor on follow-up compliance rate (93.2% vs. 92.3%). The reporting
      rate of atypical squamous cells (ASC) decreased from 17.1 to 14.7 per 1000
      (ratio, 0.86; 95% CI, 0.81-0.91), the total positivity rate from 31.1 to 29.0 per
      1000 (ratio, 0.93; 95% CI, 0.90-0.97), and the ASC:SIL (squamous intraepithelial
      lesion) ratio from 1.38 to 1.16. Compared with the ASCUS (ASC of undetermined
      significance) reports of TBS 1991, the predictive value for CIN2-3/carcinoma
      decreased from 5.2 to 3.5% (ratio, 0.68; 95% CI, 0.48-0.93) among ASCUS reports,
      but increased from 5.1 to 17.2% (ratio, 3.41; 95% CI, 1.64-6.28) among ASC-cannot
      exclude high grade lesion (ASC-H) reports. ASC-H had a 5.01-fold (95% CI, 2.23
      10.2) greater predictive value than ASCUS. CONCLUSIONS: TBS 2001 is applicable to
      cervical screening in a public health setting.

PMID- 16948128
TI  - Development and validation of nomograms for predicting residual tumor size and
      the probability of successful conservative surgery with neoadjuvant chemotherapy
      for breast cancer.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NACT) increases the likelihood that breast
      conservation therapy for breast cancer patients will be successful. There is no
      available nomogram to predict breast conservation after NACT. The aim of the
      current study was to develop and validate nomograms for predicting residual tumor
      size and probability of a patient becoming eligible for breast conservation
      surgery after NACT. METHODS: A total of 1147 patients treated at M. D. Anderson
      Cancer Center (Houston, TX) and the Institut Gustave Roussy (Villejuif, France)
      who received anthracycline with or without paclitaxel NACT were included in the
      analysis. Clinicopathologic data from 1 series were used to construct logistic
      regression models for breast conservation and residual tumor size < 3 cm after
      NACT and were validated on an independent series. RESULTS: The discrimination and
      the calibration of the nomogram for predicting the probability of residual tumor
      size < 3 cm after anthracycline-based NACT were good when applied to the
      validation set (concordance index = 0.79; U-index = 10(-3)). The discrimination
      of the nomogram for predicting eligibility for breast conservation therapy was
      also good (concordance index = 0.67). However, the calibration had to be adjusted
      to take into account global rates of breast conservation surgery. A second
      nomogram adapted to preoperative chemotherapy regimens containing paclitaxel was
      established. The concordance index of the nomogram for predicting breast
      conservation was 0.71 (P < 10(-6)) for the independent dataset and the
      calibration was also good. The confrontation of both nomograms showed that
      predictions were highly correlated (r = 0.97), suggesting that eligibility for
      breast conservation therapy was independent of the preoperative chemotherapy
      regimen used. CONCLUSIONS: Nomograms were developed for breast cancer patients
      who received NACT to predict residual tumor size and whether the patient would
      thus become eligible for breast conservation therapy. These tools may be useful
      when counseling patients about treatment options, and a web-based interface is
      now available to help guide patients and physicians in these decisions.

PMID- 16948129
TI  - Mutational analysis of protein solubility enhancement using short peptide tags.
AB  - Protein aggregation is a common phenomenon. The preparation of highly
      concentrated protein samples, typically required for biophysical measurements,
      often involves a time consuming and tedious testing of solvent conditions for
      improving protein solubility. Here, in a systematic analysis, we have determined
      the increase in solubility upon the addition of SEP-tags (solubility enhancement
      peptide tags) containing, one, three, and five lysines or arginines (or six
      arginines) to either the N or C terminus of our low solubility model protein,
      bovine pancreatic trypsin inhibitor variant, BPTI-22 (a BPTI variant containing
      22 alanines). As anticipated, the BPTI-22 solubility increased in direct relation
      to the number of charged residues contained in the SEP-tag, and without altering
      either the activity or the structure of the protein. The largest solubility
      increases were of 4.2-, 4.8-, and 6.2-folds produced by the addition, at the C
      terminus, of five lysine (BPTI-22-C5K), five and six arginine residues (BPTI-22
      C5R and BPTI-22-C6R), respectively. The increased solubility of the tagged BPTI
      22 yielded higher quality NMR spectra (hetero single quantum correlation HSQC
      spectra; with respect of the signal-to-noise and line shapes) in a much shorter
      time than for the untagged BPTI-22. Furthermore, tagged samples remained soluble
      for over ten days, as observed by their HSQC spectra. We believe that lysine- and
      arginine-based SEP-tags may provide an effective and versatile method for
      enhancing protein solubility.

PMID- 16948131
TI  - Notice of retraction: "Pathologic indicators of degradation and inflammation in
      human osteoarthritic cartilage are abrogated by exposure to n-3 fatty acids"
      (Arthritis Rheum 2002;46:1544-53).

PMID- 16948130
TI  - Increased collagen degradation around loosened total hip replacement implants.
AB  - OBJECTIVE: To assess collagen degradation and its relationship to some of the key
      collagenolytic proteinases in the aggressive synovial membrane-like interface
      tissue around aseptically loosened hip replacement implants. METHODS: The medical
      indication for the primary total hip replacement was osteoarthritis in all study
      patients. Samples from the study patients were compared with control synovial
      membranes obtained from trauma (hip fracture) patients. Proteoglycans were
      extracted with 4M guanidinium chloride. Denatured collagen in the remaining
      matrix was solubilized with alpha-chymotrypsin. Nonsoluble matrix and supernatant
      fractions were acid hydrolyzed before measurement of hydroxyproline. The
      proportion of soluble (in vivo-degraded) collagen of the total sample collagen
      content was calculated. Proteinases were stained using the avidin-biotin
      peroxidase complex method. RESULTS: Collagen in the interface membrane from the
      implants was highly degraded (mean +/- SEM 20 +/- 3%) compared with that in the
      control synovial membranes (12 +/- 1%; P = 0.007). In controls, the degree of
      collagen degradation did not correlate with levels of matrix metalloproteinase 1
      (MMP-1), MMP-13, or cathepsin K, although MMP-1 approached statistical
      significance. In interface membranes, the correlations were r = 0.88 (P = 0.002),
      r = 0.92 (P = 0.001), and r = 0.98 (P < 0.0001) for MMP-1, MMP-13, and cathepsin
      K, respectively. CONCLUSION: In normal synovial membrane, collagen matrix
      remodeling may be mainly an intracellular process. In contrast, pathologic tissue
      destruction in the interface membrane from prosthetic hip joints is associated
      with a shift toward MMP-13 and cathepsin K, which become activated and overcome
      their endogenous inhibitors (tissue inhibitors of metalloproteinases and cystatin
      C). The highly significant correlation between collagen degradation and cathepsin
      K indicates an extracellular role of this acidic endoproteinase, consistent with
      previous observations concerning the acidity of the interface membrane.

PMID- 16948132
TI  - Cappuccino mutation in an autoimmune-prone strain of mice suggests a role of
      platelet function in the progression of immune complex crescentic
      glomerulonephritis.
AB  - OBJECTIVE: Crescent formation in the renal glomerulus is a typical manifestation
      of progressive glomerulopathy associated with fatal renal failure; therefore, its
      prevention is of clinical importance. Little is known about the pathogenic
      mechanism for crescent formation. This study was undertaken in an attempt to
      identify the events that are critical for crescent formation in immune complex
      crescentic glomerulonephritis (CGN) by analyzing a novel mutant strain of mice.
      METHODS: A spontaneous mutant strain of mice was isolated from the autoimmune
      prone strain EOD, which stably develops fatal CGN. The mutant phenotypes were
      assessed histopathologically, hematologically, and immunologically. The mutation
      was searched for with positional cloning using microsatellite markers. RESULTS:
      Compared with wild-type EOD (WT-EOD) mice, mutant EOD (mut-EOD) mice showed
      marked improvement in CGN in conjunction with an improvement in spontaneous
      mortality. In WT-EOD mice, an inverse correlation between blood urea nitrogen
      concentration and blood platelet count and massive accumulation of platelets in
      the glomerulus were evident, suggesting that an accumulation of platelets in the
      glomerulus contributes to the progression of CGN. The mutant platelets showed an
      abnormal aggregation in response to collagen and thrombin, associated with a
      bleeding tendency in mut-EOD mice. Genetic analysis revealed a deleterious
      mutation in the cappuccino gene (cno), which encodes a protein that belongs to a
      complex called the biogenesis of lysosome-related organelle complex 1 and is
      profoundly involved in platelet function. Morphologic examination revealed a
      partial defect in dense body formation in the delta-granule of platelets.
      CONCLUSION: The present findings suggest that platelet functions have a critical
      role in crescent formation in autoimmune GN.

PMID- 16948133
TI  - Chimerism occurs twice as often in lupus nephritis as in normal kidneys.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is an immune-mediated disease that
      particularly affects the kidneys, causing lupus nephritis. In experimental mouse
      models, lupus nephritis can be mimicked by inducing a chimeric state through the
      injection of parental T cells in offspring. In humans, pregnancy-induced
      chimerism may play a role in the pathogenesis of autoimmune diseases such as SLE,
      but it is likely that only certain chimeric cells have pathogenic potential. In
      this study, we investigated whether the distribution of chimeric cells is
      different in the kidneys of women with SLE from that in normal kidneys, and we
      examined the phenotype of chimeric cells in women with SLE. METHODS: The presence
      of chimeric cells was investigated by in situ hybridization targeting the Y
      chromosome in 57 renal biopsy samples from 49 women with lupus nephritis. Fifty
      one kidney autopsy specimens without histomorphologic lesions served as controls.
      Double-staining for the Y chromosome in combination with CD3 and CD34 markers was
      performed in 5 kidney specimens with lupus nephritis to identify the phenotype of
      the chimeric cells. RESULTS: Y chromosome-positive cells were found in 27 of 49
      patients with lupus nephritis and in 13 of 51 normal controls (P < 0.01). Both
      CD3+ and CD34+ chimeric cells were identified in lupus nephritis kidney
      specimens. CONCLUSION: Chimeric cells are present significantly more often in
      kidneys with lupus nephritis than in normal kidneys, and some of these chimeric
      cells are T cells. This finding is interesting in light of experimental models
      demonstrating that lupus nephritis is initiated by chimeric T cells.

PMID- 16948134
TI  - Differential expression of stromal cell-derived factor 1 and its receptor CXCR4
      in the skin and endothelial cells of systemic sclerosis patients: Pathogenetic
      implications.
AB  - OBJECTIVE: Systemic sclerosis (SSc) is characterized by early endothelial damage
      evolving to vascular desertification. Stromal cell-derived factor 1 (SDF-1) and
      its receptor CXCR4 regulate specific steps in new vessel formation. We undertook
      this study to determine whether an alteration of the SDF-1/CXCR4 axis might be
      involved in the pathogenetic mechanisms following ischemic damage during SSc.
      METHODS: We enrolled 36 SSc patients and 15 controls. Skin biopsy samples were
      obtained from each subject, and the expression of SDF-1 and CXCR4 was assessed by
      immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR),
      and Western blot analyses. Furthermore, isolated microvascular endothelial cells
      (MVECs) from 4 patients with diffuse cutaneous SSc (dcSSc) and 3 controls were
      analyzed for SDF-1 and CXCR4 by confocal laser scanning microscopy, RT-PCR, and
      Western blotting. RESULTS: SDF-1 and CXCR4 were up-regulated in the skin of
      patients with early (edematous) SSc, both in the diffuse and limited cutaneous
      forms, and progressively decreased, with the lowest expression in the latest
      phases of both SSc subsets. MVECs from patients with dcSSc expressed
      significantly higher amounts of both isoforms of SDF-1 in the early stage of
      disease, with a progressive reduction of SDF-1 and CXCR4 in later stages. On the
      surface of cultured MVECs from patients with dcSSc, SDF-1 and CXCR4 colocalized
      in polarized areas, suggesting that they are activated in vivo and that they are
      under strict genetic control to retain capping function. CONCLUSION: Due to its
      transient expression, SDF-1 could be considered a future therapeutic target to
      induce new vessel formation in SSc.

PMID- 16948135
TI  - Nucleolar staining cannot be used as a screening test for the scleroderma marker
      anti-RNA polymerase I/III antibodies.
AB  - OBJECTIVE: Anti-RNA polymerase I/III (anti-RNAP I/III) antibodies are clinically
      useful markers of scleroderma, and their presence is associated with diffuse skin
      disease and an increased risk of cardiac and kidney involvement. Although RNAP I
      antibodies localize to the nucleolus, nucleolar staining by many anti-RNAP
      antibody-positive sera is not always observed. Nucleolar staining by anti-RNAP
      antibody-positive sera was examined by double staining with antifibrillarin
      antibodies to evaluate whether nucleolar staining can be used as a screening test
      for anti-RNAP I/III antibodies. In addition, the relationships between nucleolar
      staining and levels of anti-RNAP III antibodies were examined by enzyme-linked
      immunosorbent assay (ELISA) and immunoprecipitation (IP) assay. METHODS: Sera
      were tested using immunofluorescent antinuclear antibodies on HEp-2 cell slides,
      by anti-RNAP III ELISA, and by IP assay using (35)S-labeled K562 cell extract.
      Nucleolar staining by anti-RNAP antibody IP-positive sera was confirmed by double
      staining using antifibrillarin monoclonal antibodies. The levels of anti-RNAP III
      antibodies were quantitated by ELISA and by IP assay using a serially diluted
      reference serum as a standard, and their relationship was analyzed. RESULTS: All
      18 anti-RNAP I/III antibody-positive sera showed nuclear speckled patterns, but
      nucleolar staining was readily noticeable in only 44% of the sera. A positive
      correlation was found between ELISA and IP units for anti-RNAP III antibodies.
      The levels of anti-RNAP III antibodies and anti-RNAP I antibodies correlated
      well, with the exception of a few sera. Levels of anti-RNAP III antibodies were
      low in sera with nucleolar staining, whereas several sera with high levels of
      anti-RNAP I antibodies clearly showed nucleolar staining. CONCLUSION: Although
      some sera positive for anti-RNAP I/III antibodies clearly stain nucleoli,
      nucleolar staining is inconsistent and cannot be used to screen for anti-RNAP
      I/III antibodies.

PMID- 16948136
TI  - Anti-cyclic citrullinated peptide antibody and rheumatoid factor isotypes in
      African Americans with early rheumatoid arthritis.

PMID- 16948137
TI  - Clinical images: Hidden in the heart.

PMID- 16948138
TI  - Effect of tumor necrosis factor alpha inhibition on CD28 surface expression on
      CD4+ T cells.

PMID- 16948140
TI  - Trial of etanercept and methotrexate with radiographic and patient outcomes two
      year clinical and radiographic results: Comment on the article by van der Heijde
      et al.

PMID- 16948141
TI  - Reconstitution of B cells after B cell-depletion therapy: Comment on the article
      by Leandro et al.

PMID- 16948142
TI  - Cultivation of MC3T3-E1 cells on a newly developed material (Sponceram) using a
      rotating bed system bioreactor.
AB  - The influence of a 3D macroporous scaffold (Sponceram) on the differentiation
      process into bone cells was investigated under static conditions in cell culture
      dishes. Furthermore, cultivations were performed using a new bioreactor system in
      the presence or absence of bone morphogenetic protein 2 (BMP-2). Preosteoblastic
      MC3T3-E1 cells were first cultured on Sponceram scaffolds in 96-well dishes using
      standard medium, differentiation medium and BMP-2 medium. Cell proliferation
      showed a similar course for all conditions used. Alkaline phosphatase (AP)
      activity resulted in a maximum at day 5 in the presence of BMP-2. Two bioreactor
      cultivations were performed in a BIOSTAT Bplus RBS (rotating bed system) 500 on
      Sponceram carrier discs. One cultivation was performed using standard medium. The
      second one was used with the same medium with BMP-2 substituted. Significant
      calcification of the extracellular matrix in the presence of BMP-2 occurred but
      even in the absence of BMP-2 mineralization was observed. mRNA expression of
      collagen I, osteocalcin and bone sialoprotein was detected after both reactor
      cultivations. This study demonstrates that macroporous Sponceram is suitable for
      the cultivation and differentiation of MC3T3-E1 cells into the osteoblastic
      phenotype. The results of the bioreactor cultivation revealed that the scaffold
      promoted the differentiation process even in the absence of BMP-2.

PMID- 16948143
TI  - Gradient substrate assembly for quantifying cellular response to biomaterials.
AB  - Using quantitative fluorescence microscopy in conjunction with a method of
      gradient substrate assembly established in their group, the authors were able to
      introduce and measure reproducible changes in cellular morphology and cell
      density by manipulating polymer grafting density. The mechanism behind this
      change in cellular behavior was explained by a semiempirical, geometric model
      that describes the effect of the spatial distribution of the polymer on protein
      attachment. A 10-fold increase in graft density of poly(2-hydroxyethyl
      methacrylate) [PHEMA] along the surface of a gradient sample, preexposed to
      bovine fibronectin, caused a change in the size of fibroblasts on the surface
      (i.e., cell spreading) from (1238 +/- 704) to (377 +/- 216) microm(2). The
      results were in quantitative agreement with those obtained on three separate
      gradient samples. Both cellular response and fibronectin adsorption (as measured
      via ellipsometry) were found to vary sigmoidally with graft density of PHEMA,
      demonstrating the high degree of correlation between the two phenomena. A simple,
      rigid-disk model accounting for the surface coverage of PHEMA was able to predict
      the amount of adsorbed fibronectin with a correlation coefficient of 0.97.
      Maximal cell adhesion and cell spreading were found to occur at fibronectin
      surface densities of 50 and 100 ng/cm(2), respectively. The results demonstrate
      the role of gradient substrate assembly as a method for quantifying the
      relationship between protein and cellular response to technologically relevant
      polymeric materials.

PMID- 16948145
TI  - RGD peptide-conjugated poly(dimethylsiloxane) promotes adhesion, proliferation,
      and collagen secretion of human fibroblasts.
AB  - A novel technique for conjugating Arg-Gly-Asp (RGD) peptides to
      poly(dimethylsiloxane) (PDMS) surfaces as well as its application to cell culture
      is presented in this paper. This technique performs RGD conjugation to PDMS
      through photochemical immobilization of functional NHS groups to PDMS surface
      followed with linking RGD peptide to the surface via coupling reaction with NHS.
      A bifunctional photolinker, N-sulfosuccinimidyl-6-(4'-azido-2'
      nitrophenylamino)hexanoate (sulfo-SANPAH), was used to conjugate RGD peptide to
      the surface. Compared to existing methods for peptide conjugation to PDMS, this
      technique is convenient, efficient, and free of organic contamination to PDMS
      surfaces. It can also be used to conjugate other peptides or proteins to most
      polymeric materials. In addition, cell culture studies showed that the RGD
      conjugated PDMS surfaces promoted the adhesion, proliferation, and collagen
      production of human skin fibroblasts (HSFs). Finally, the RGD-conjugated PDMS
      surfaces are resistant to autoclaving and UV irradiation, which enables them to
      be repeatedly used in cell culture studies.

PMID- 16948146
TI  - Co-electrospun poly(lactide-co-glycolide), gelatin, and elastin blends for tissue
      engineering scaffolds.
AB  - In this study, we describe composite scaffolds composed of synthetic and natural
      materials with physicochemical properties suitable for tissue engineering
      applications. Fibrous scaffolds were co-electrospun from a blend of a synthetic
      biodegradable polymer (poly(lactic-co-glycolic acid), PLGA, 10% solution) and two
      natural proteins, gelatin (denatured collagen, 8% solution) and alpha-elastin
      (20% solution) at ratios of 3:1:2 and 2:2:2 (v/v/v). The resulting PLGA-gelatin
      elastin (PGE) fibers were homogeneous in appearance with an average diameter of
      380 +/- 80 nm, which was considerably smaller than fibers made under identical
      conditions from the starting materials (PLGA, 780 +/- 200 nm; gelatin, 447 +/-
      123 nm; elastin, 1060 +/- 170 nm). Upon hydration, PGE fibers swelled to an
      average fiber diameter of 963 +/- 132 nm, but did not disintegrate. Importantly,
      PGE scaffolds were stable in an aqueous environment without crosslinking and were
      more elastic than those made of pure elastin fibers. To investigate the
      cytocompatibility of PGE, we cultured H9c2 rat cardiac myoblasts and rat bone
      marrow stromal cells (BMSCs) on fibrous PGE scaffolds. We found that myoblasts
      grew equally as well or slightly better on the scaffolds than on tissue-culture
      plastic. Microscopic evaluation confirmed that myoblasts reached confluence on
      the scaffold surfaces while simultaneously growing into the scaffolds.
      Histological characterization of the PGE constructs indicated that BMSCs
      penetrated into the center of scaffolds and began proliferating shortly after
      seeding. Our results suggest that fibrous scaffolds made of PGE and similar
      biomimetic blends of natural and synthetic polymers may be useful for engineering
      soft tissues, such as heart, lung, and blood vessels.

PMID- 16948147
TI  - Replication in genetic association studies: Comment on the editorial by Spector
      et al.

PMID- 16948148
TI  - Therapeutic effects for hypersensitivity pneumonitis induced by Japanese mushroom
      (Bunashimeji).
AB  - BACKGROUND: Bunashimeji-related hypersensitivity pneumonitis is found among
      workers who cultivate the mushroom in indoor facilities. An evaluation of
      protective measures was initiated using the outcomes of clinical, immunological,
      and radiological findings. METHODS: Twenty-two patients presented with symptoms
      of HP; all were employed cultivating Bunashimeji mushrooms in indoor facilities.
      After hospitalization, 6 of 22 patients quit their job to avoid exposure to
      spores (Avoidance group). Sixteen patients continued to work used a mask for 3
      months, and were then divided into two subgroups: Mask alone (seven patients) and
      mask plus oral prednisolone (Mask + PSL) (nine patients). The erythrocyte
      sedimentation rate (ESR), serum Krebs von der Lungen-6 (KL-6), surfactant protein
      D (SP-D), lymphocyte stimulation test (LST), ground-glass scores in chest high
      resolution computed tomography (HRCT), and bronchoalveolar lavage (BAL) were
      assessed before and after treatment. RESULTS: Complete avoidance resulted in a
      significant decrease in LST. There was a significant decrease after PSL treatment
      in serum KL-6, SP-D, and total cell counts in the BAL fluid in the Mask + PSL
      group. In the Mask alone group, serum KL-6, SP-D, ground-glass scores in chest
      HRCT and total cell counts in BAL fluid showed high levels compared with the
      other two groups. CONCLUSIONS: Complete cessation was the best treatment for
      hypersensitivity pneumonitis. The use of a mask was ineffective for patients with
      a high serum KL-6 and SP-D concentration and severe ground-glass opacity on chest
      HRCT. Initial treatment with PSL is recommended for these patients with high
      levels of total cell counts in BAL fluid.

PMID- 16948149
TI  - Patterns of fatigue among seafarers during a tour of duty.
AB  - BACKGROUND: Work-related fatigue is associated with sickness absence and mental
      and physical health problems, and may increase the risk of accidents and injuries
      at work. Relatively little is known about fatigue among seafarers, particularly
      during a tour of duty. The aim of this study was to describe the pattern of day
      to day fatigue among seafarers during a tour at sea. METHODS: Participants from
      the offshore support, short sea and coastal, and deep sea sectors of the UK
      shipping industry completed daily diaries. Information about sleep and fatigue
      was collected each day on waking and retiring. RESULTS: Fatigue on waking was a
      more sensitive measure of cumulative occupational fatigue than fatigue on
      retiring. Fatigue on waking increased between the start and end of tour. This
      increase took place in particular during the first week at sea, and was most
      apparent among those on shorter tours of duty. CONCLUSIONS: Day to day changes in
      fatigue are measurable, and may vary among particular sub-groups of seafarers.
      Used among larger groups, such a diary method could help identify times and
      activities associated with the greatest risk.

PMID- 16948151
TI  - Treatment of localized scleroderma in childhood: Comment on the article by Zulian
      et al.

PMID- 16948155
TI  - Measures for the assessment of fuzzy predictions of protein secondary structure.
AB  - Many of the recent secondary structure prediction methods incorporate the idea of
      fuzzy set theory, where instead of assigning a definite secondary structure to a
      query residue, probability for the residue being in each of the conformational
      states is estimated. Moreover, continuous assignment of conformational states to
      the experimentally observed protein structures can be performed in order to
      reflect inherent flexibility. Although various measures have been developed for
      evaluating performances of secondary structure prediction methods, they depend
      only on the most probable secondary structures. They do not assess the accuracy
      of the probabilities produced by fuzzy prediction methods, and they cannot
      incorporate information contained in continuous assignments of conformational
      states to observed structures. Three important measures for evaluating
      performance of a secondary structure prediction algorithm, Q score, Segment
      OVerlap (SOV) measure, and the k-state correlation coefficient (Corr), are
      deformed into fuzzy measures F score, Fuzzy OVerlap (FOV) measure, and the fuzzy
      correlation coefficient (Forr), so that the new measures not only assess
      probabilistic outputs of fuzzy prediction methods, but also incorporate
      information from continuous assignments of secondary structure. As an example of
      application, prediction results of four fuzzy secondary structure prediction
      methods, PSIPRED, PROFking, SABLE, and PREDICT, are assessed using the new fuzzy
      measures.

PMID- 16948156
TI  - Molecular dynamics study of the stabilities of consensus designed ankyrin repeat
      proteins.
AB  - Two designed ankyrin repeat (AR) proteins (E3_5 and E3_19) are high homologous
      (with about 87% sequence identity) and their crystal structures have a Calpha
      atom-positional root-mean-square difference of about 0.14 nm. However, it was
      found that E3_5 is considerably more stable than E3_19 in guanidinium
      hydrochloride and thermal denaturation experiments. With the goal of providing
      insights into the various factors contributing to the stabilities of the designed
      AR proteins and suggesting possible mutations to enhance their stabilities,
      homology modeling and molecular dynamics (MD) simulations with explicit solvent
      have been performed. Because the crystal structure of E3_19 was solved later than
      that of E3_5, a homology model of E3_19 based on the crystal structure of E3_5
      was also used in the simulations. E3_5 shows a very stable trajectory in both
      crystal and solution simulations. In contrast, the C-terminal repeat of E3_19
      unfolds in the simulations starting from either the modeled structure or the
      crystal structure, although it has a sequence identical to that of E3_5. A
      continuum electrostatic model was used to estimate the effect of single mutations
      on protein stability and to study the interaction between the internal ARs and
      the C-terminal capping AR. Mutations involving charged residues were found to
      have large effects on stability. Due to the difference in charge distribution in
      the internal ARs of E3_19 and E3_5, their interaction with the C-terminal capping
      AR is less favorable in E3_19. The simulation trajectories suggest that the
      stability of the designed AR proteins can be increased by optimizing the
      electrostatic interactions within and between the different repeats.

PMID- 16948157
TI  - Long working hours, safety, and health: toward a National Research Agenda.
AB  - BACKGROUND: A significant and growing number of people work long hours. Research
      examining impacts is limited, but raises concerns about risks to the worker, the
      family, the employer, and the community. The purpose of this report, which is
      authored by the National Occupational Research Agenda (NORA) Long Work Hours
      Team, is to motivate and guide future research by proposing a framework for
      studying long work hours and discussing research gaps. METHODS: The NORA Long
      Work Hours Team examined research reports and literature reviews, and gathered
      input from a conference on long work hours organized by the Team and faculty from
      University of Maryland. RESULTS AND CONCLUSION: A framework is proposed for long
      work hours, including determinants, outcomes, and moderating factors of long work
      hours, suggesting that studies need to include more clear and complete
      descriptions of work schedules, worker characteristics, and the work environment,
      and need to consider a wider range of possible health, safety, social and
      economic outcomes for workers, families, employers, and the community. Additional
      studies are needed on vulnerable employee groups and those critical to public
      safety. More studies are also needed to develop interventions and test their
      effectiveness.

PMID- 16948158
TI  - Crystal structure of an ORFan protein (TM1622) from Thermotoga maritima at 1.75 A
      resolution reveals a fold similar to the Ran-binding protein Mog1p.

PMID- 16948159
TI  - An efficient and generic strategy for producing soluble human proteins and
      domains in E. coli by screening construct libraries.
AB  - The implementation of generic and efficient technologies for the production of
      recombinant eukaryotic proteins remains an outstanding challenge in structural
      genomics programs. We have recently developed a new method for rapid
      identification of soluble protein expression in E. coli, the colony filtration
      blot (CoFi blot). In this study, the CoFi blot was used to screen libraries where
      the N-terminal translation start point was randomized. To investigate the
      efficiency of this strategy, we have attributed a large number of proteins to
      this process. In a set of 32 mammalian proteins, we were able to double the
      success rate (from 34 to 68%) of producing soluble and readily purifiable
      proteins in E. coli. Most of the selected constructs had their N-termini close to
      predicted domain borders and the method therefore provides a mean for
      experimental "domain foot printing." Surprisingly, for most of the targets, we
      also observed expressing constructs that were close to full-length. In summary
      this strategy constitutes a generic and efficient method for producing mammalian
      proteins for structural and functional studies.

PMID- 16948160
TI  - Specificity of molecular interactions in transient protein-protein interaction
      interfaces.
AB  - In this study, we investigate what types of interactions are specific to their
      biological function, and what types of interactions are persistent regardless of
      their functional category in transient protein-protein heterocomplexes. This is
      the first approach to analyze protein-protein interfaces systematically at the
      molecular interaction level in the context of protein functions. We perform
      systematic analysis at the molecular interaction level using classification and
      feature subset selection technique prevalent in the field of pattern recognition.
      To represent the physicochemical properties of protein-protein interfaces, we
      design 18 molecular interaction types using canonical and noncanonical
      interactions. Then, we construct input vector using the frequency of each
      interaction type in protein-protein interface. We analyze the 131 interfaces of
      transient protein-protein heterocomplexes in PDB: 33 protease-inhibitors, 52
      antibody-antigens, 46 signaling proteins including 4 cyclin dependent kinase and
      26 G-protein. Using kNN classification and feature subset selection technique, we
      show that there are specific interaction types based on their functional
      category, and such interaction types are conserved through the common binding
      mechanism, rather than through the sequence or structure conservation. The
      extracted interaction types are C(alpha)-- H...O==C interaction, cation...anion
      interaction, amine...amine interaction, and amine...cation interaction. With
      these four interaction types, we achieve the classification success rate up to
      83.2% with leave-one-out cross-validation at k = 15. Of these four interaction
      types, C(alpha)--H...O==C shows binding specificity for protease-inhibitor
      complexes, while cation-anion interaction is predominant in signaling complexes.
      The amine ... amine and amine...cation interaction give a minor contribution to
      the classification accuracy. When combined with these two interactions, they
      increase the accuracy by 3.8%. In the case of antibody-antigen complexes, the
      sign is somewhat ambiguous. From the evolutionary perspective, while protease
      inhibitors and sig-naling proteins have optimized their interfaces to suit their
      biological functions, antibody-antigen interactions are the happenstance,
      implying that antibody-antigen complexes do not show distinctive interaction
      types. Persistent interaction types such as pi...pi, amide-carbonyl, and hydroxyl
      carbonyl interaction, are also investigated. Analyzing the structural
      orientations of the pi...pi stacking interactions, we find that herringbone shape
      is a major configuration in transient protein-protein interfaces. This result is
      different from that of protein core, where parallel-displaced configurations are
      the major configuration. We also analyze overall trend of amide-carbonyl and
      hydroxyl-carbonyl interactions. It is noticeable that nearly 82% of the
      interfaces have at least one hydroxyl-carbonyl interactions.

PMID- 16948161
TI  - Crystal structure of the conserved hypothetical cytosolic protein Xcc0516 from
      Xanthomonas campestris reveals a novel quaternary structure assembled by five
      four-helix bundles.

PMID- 16948162
TI  - Generalized modeling of enzyme-ligand interactions using proteochemometrics and
      local protein substructures.
AB  - Modeling and understanding protein-ligand interactions is one of the most
      important goals in computational drug discovery. To this end, proteochemometrics
      uses structural and chemical descriptors from several proteins and several
      ligands to induce interaction-models. Here, we present a new and generalized
      approach in which proteins varying greatly in terms of sequence and structure are
      represented by a library of local substructures. Using linear regression and rule
      based learning, we combine such local substructures with chemical descriptors
      from the ligands to model binding affinity for a training set of hydrolase and
      lyase enzymes. We evaluate the predictive performance of these models using cross
      validation and sets of unseen ligand with unknown three-dimensional structure.
      The models are shown to generalize by outperforming models using descriptors from
      only proteins or only ligands, or models using global structure similarities
      rather than local similarities. Thus, we demonstrate that this approach is
      capable of describing dependencies between local structural properties and
      ligands in otherwise dissimilar protein structures. These dependencies are often,
      but not always, associated with local substructures that are in contact with the
      ligands. Finally, we show that strongly bound enzyme-ligand complexes require the
      presence of particular local substructures, while weakly bound complexes may be
      described by the absence of certain properties. The results demonstrate that the
      alignment-independent approach using local substructures is capable of describing
      protein-ligand interaction for largely different proteins and hence opens up for
      proteochemometrics-analysis of the interaction-space of entire proteomes. Current
      approaches are limited to families of closely related proteins. families of
      closely related proteins.

PMID- 16948163
TI  - Prevalence of building-related symptoms as an indicator of health and
      productivity.
AB  - BACKGROUND: The prevalence of building-related symptoms (BRS) is commonly used to
      characterize the indoor air quality in office buildings. To analyze the costs of
      building renovation and the improvement of the indoor environment, it is useful
      to quantitatively relate the prevalence or intensity of BRS to productivity. The
      intent of this study is to summarize the links between the BRS and productivity,
      and demonstrate this linkage in two case buildings. MATERIAL AND METHODS: A
      literature was surveyed for studies that measured simultaneously the prevalence
      or intensity of BRS and subjectively reported or objectively measured
      productivity. Case studies in two office environments were performed. An
      association between the prevalence of BRS and productivity of workers in a call
      center and in an insurance office were investigated. In the first case study, the
      productivity was expressed using the direct productivity metrics, namely the
      number of telephone contacts during active working hours while in the second
      case, the productivity was assessed by using the data concerning sick leave
      rates. RESULTS: Employees who report more BRS also have more often absences which
      relate to indoor environment quality (IEQ). Their productivity is lower than
      those who have better IEQ in their offices. Despite uncertainties related to the
      data concerning recorded sick leave and self-reported productivity, the number of
      studies showing an association between BRS and productivity or sick leave
      suggests that such a relationship exists. The present case studies also
      demonstrated an association between the BRS and the direct productivity. Based on
      the data from the call center, a reduction of 10%-units in the prevalence of
      general symptoms (such as fatigue, headache, nausea, etc.) corresponded with a
      gain of 1.5% in performance. Based on the findings in the insurance company, a
      reduction of 10%-units in the prevalence of irritation symptoms corresponded with
      a decrease of 0.7% in the short-term absenteeism. CONCLUSIONS: A review of 23
      studies suggests that a linkage exists between typical BRS and productivity
      indicators such as task or work performance or absence from work. Quantitative
      associations between BRS and productivity were demonstrated in two office
      environments. Quantitative associations between BRS and economic metrics enable
      cost-benefits analysis.

PMID- 16948164
TI  - Selective modification of surface-exposed thiol groups in Trigonopsis variabilis
      D-amino acid oxidase using poly(ethylene glycol) maleimide and its effect on
      activity and stability of the enzyme.
AB  - Covalent modification of purified Trigonopsis variabilis D-amino acid oxidase
      using maleimide-activated poly(ethylene glycol) 5000 yielded a stable
      bioconjugate in which three surface-exposed cysteine side chains were selectively
      derivatized. Compared with the native enzyme, the PEGylated variant displayed
      substantially (approximately 3.3-fold) slowed dissociation rate of FAD cofactor
      at 50 degrees C, and this caused a twofold thermostabilization of the enzyme
      activity. The stability under reaction conditions at 30 degrees C was also
      markedly enhanced in the PEG-oxidase conjugate. PEGylation did not affect steady
      state kinetic parameters for oxidative deamination of D-methionine when 2,6
      dichloroindophenol replaced dioxygen as the cosubstrate while it caused a
      ninefold decrease in substrate catalytic efficiency for the dioxygen-dependent
      reaction.

PMID- 16948165
TI  - Chemometric analysis of in-line multi-wavelength fluorescence measurements
      obtained during cultivations with a lipase producing Aspergillus oryzae strain.
AB  - The filamentous fungus, Aspergillus oryzae, was cultivated in batch and fed-batch
      cultivations in order to investigate the use of multi-wavelength fluorescence for
      monitoring course of events during filamentous fungi cultivations. The A. oryzae
      strain applied expressed a fungal lipase from Thermomyces lanuginosus. Spectra of
      multi-wavelength fluorescence were collected every 5 min with the BioView system
      (DELTA, Denmark) and both explorative and predictive models, correlating the
      fluorescence data with cell mass and lipase activity, were built. During the
      cultivations, A. oryzae displayed dispersed hyphal growth and under these
      conditions no fouling of the multi-wavelength fluorescence sensor was observed.
      The scores of a parallel factor analysis (PARAFAC) model, based on the
      fluorescence spectra, gave clear evidence of, for example, the on-set of the
      feeding phase. The predictive models, estimating the cell mass, showed
      correlations between 0.73 and 0.97 with root mean square error of cross
      validation (RMSECV) values between 1.48 and 0.77 g . kg(-1). A model estimating
      the lipase activity was also constructed for the fed-batch cultivations with a
      correlation of 0.93. The results presented here clearly show that multi
      wavelength fluorescence is a useful tool for monitoring fed-batch cultivations of
      filamentous fungi.

PMID- 16948166
TI  - Quantitation of interaction of lipids with polymer surfaces in cell culture.
AB  - As cell culture medium development efforts have progressed towards leaner, serum
      free, and chemically defined formulations, it has become increasingly important
      to ensure that the appropriate concentrations of all nutrients are maintained and
      delivered at point of use. In light of concurrent efforts to progress to
      disposable polymeric storage and culture platforms, the characterization and
      control of medium component interactions with container surfaces can be a key
      issue in ensuring consistent delivery of these medium formulations. These studies
      characterize the interactions of lipids with culture surfaces typically
      encountered in the bioprocess industry using model systems. The extent and
      kinetics of lipid association with polymeric surfaces were determined using radio
      labeled linoleic acid and cholesterol. The effect of methyl-beta-cyclodextrin, a
      component commonly used to solubilize lipids in culture media, on association
      kinetics was also examined. In addition, loss of lipids across a sterilizing
      membrane filter was quantified. We find that there is potential for significant
      loss of hydrophobic components due to non-specific binding to surfaces at
      timescales relevant to a typical cell culture process. The extent of loss is
      dependent on the nature of the hydrophobic component as well as the type of
      surface. These studies highlight the potential of the extracellular environment
      to modify medium composition and also emphasize the importance of medium
      formulation strategies, including those used in the delivery of hydrophobic
      components. It is noted, however, that the level of loss is very dependent on the
      specific system including the composition of the culture medium used.

PMID- 16948167
TI  - Effect of solvent concentration on the extraction kinetics and diffusivity of
      Cyclosporin A in the fungus Tolypocladium inflatum.
AB  - The kinetics of solid-liquid extraction and extraction yields of the
      immunosuppressant drug Cyclosporin A (CyA) from the mycelia of Tolypocladium
      inflatum were examined in this study. A 2 L stirred, baffled vessel was used to
      extract CyA from wet mycelia mass. Three different organic solvents were used,
      namely, methanol, acetone, and isopropanol at different concentrations in aqueous
      mixtures at room temperature. It was found that the best solvent was acetone at
      50% v/v concentration achieving 100% extraction of CyA from the mycelia of T.
      inflatum. Although acetone proved to be the better solvent for CyA extraction,
      further studies were performed using methanol. A linear relationship was found
      between extraction yield of CyA and methanol concentration with 100% CyA
      extraction at 90% v/v methanol. The partition coefficients of CyA between the
      solid mycelia phase and the aqueous solvent phase were found to decrease
      exponentially with increasing methanol concentration. A liquid extraction model
      was developed based on the diffusion equation to correlate the kinetic data of
      CyA extraction from the solid mycelia of T. inflatum. Non-linear regression
      analysis of experimental data was used with the diffusion equation in order to
      calculate the effective diffusivities of CyA in the mycelia of T. inflatum. For
      all three organic solvents used, the effective diffusivities of CyA were found to
      be between 4.41 x 10(-15) and 6.18 x 10(-14) m(2)/s. This is the first time CyA
      effective diffusivities in T. inflatum are reported in the literature.

PMID- 16948168
TI  - Limits to productivity of the alga Pleurochrysis carterae (Haptophyta) grown in
      outdoor raceway ponds.
AB  - This study examined the effects of oxygen concentration, pond temperature and
      irradiance on productivity and CaCO(3) formation of the coccolith-forming alga,
      Pleurochrysis carterae CCMP647 grown in semi-continuous culture in outdoor
      raceway ponds. During the day the oxygen content of the pond increases markedly
      and P. carterae photosynthesis is inhibited by these high O(2) concentrations
      with the inhibition increasing with increasing temperature. The high irradiance
      outdoors presents less of a problem to photosynthesis and productivity as the
      algae can acclimate well to high irradiances over a period of several weeks. Pond
      depth also effects productivity and this effect varies with season. During
      autumn, productivities were highest at depths of 13 to 16 cm, and decreased when
      the depth was increased. During summer productivity was much lower at 13 cm pond
      depth and increased when the depth was increased to 16, 18 and 21 cm. Heating the
      ponds in the morning by approximately 3 to 5 degrees C improves productivity by
      11%-21%, presumably because this allows the algae to photosynthesise faster in
      the conditions of low [O(2)] which occur in the early morning.

PMID- 16948169
TI  - Effects of shear stress on 3-D human mesenchymal stem cell construct development
      in a perfusion bioreactor system: Experiments and hydrodynamic modeling.
AB  - Shear stress is an important biomechanical parameter in regulating human
      mesenchymal stem cell (hMSC) construct development. In this study, the
      biomechanical characteristics of hMSCs within highly porous 3-D poly (ethylene
      terephthalate) (PET) matrices in a perfusion bioreactor system were analyzed for
      two flow rates of 0.1 and 1.5 mL/min, respectively over a 20-day culture period.
      A 1.4 times higher proliferation rate, higher CFU-F formation, and more
      fibronectin and HSP-47 secretion at day 20 were observed at the flow rate of 0.1
      mL/min compared to those at the flow rate of 1.5 mL/min. The higher flow rate of
      1.5 mL/min upregulated osteogenic differentiation potential at day 20 as measured
      by the expression of alkaline phosphatase activity and calcium deposition in the
      matrix after 14 days osteogenic induction, consistent with those reported in
      literatures. Mathematical modeling indicated that shear stress existed in the
      range of 1 x 10(-5) to 1 x 10(-4) Pa in the constructs up to a depth of 70 microm
      due to flow penetration in the porous constructs. Analysis of oxygen transport in
      the constructs for the two flow rates yielded oxygen levels significantly higher
      than those at which cell growth and metabolism are affected (Jiang et al., 1996).
      This indicates that differences in convective transport have no significant
      influence on cell growth and metabolism for the range of flow rates studied.
      These results demonstrate that shear stress is an important microenvironment
      parameter that regulates hMSC construct development at a range significantly
      lower than those reported previously in the perfusion system.

PMID- 16948170
TI  - Increased heterologous protein production by Saccharomyces cerevisiae growing on
      ethanol as sole carbon source.
AB  - Saccharomyces cerevisiae is a widely used host organism for the production of
      heterologous proteins, often cultivated in glucose-based fed-batch processes.
      This production system however has many factors limiting the productivity, mainly
      towards the end of the fermentation. For the optimised production of a Camelid
      antibody fragment this process was evaluated. In shake flask cultivations, it was
      found that ethanol has a strong effect on productivity increase and therefore
      glucose and ethanol fed-batch fermentations were compared. It appeared that
      specific heterologous protein production was up to five times higher in the
      ethanol cultivation and could be further optimised. Then the key characteristics
      of ethanol fed-batch fermentations such as growth rate and specific production
      were determined under ethanol limitation and accumulation and growth limiting
      conditions in the final phase of the process. It appeared that an optimal
      production process should have an ethanol accumulation throughout the feed phase
      of approximately 1% v/v in the broth and that production remains very efficient
      even in the last phase of the process. This productivity increase on ethanol
      versus glucose was also proven for several other Camelid antibody fragments some
      of which were heavily impaired in secretion on glucose, but very well produced on
      ethanol. This leads to the suggestion that the ethanol effect on improved
      heterologous protein production is linked to a stress response and folding and
      secretion efficiency.

PMID- 16948171
TI  - Codon optimized Thermobifida fusca hydrolase secreted by Bacillus megaterium.
AB  - Production and secretion of a 28,172 Da hydrolase from Thermobifida fusca (TFH)
      in Bacillus megaterium MS941 and WH323 was investigated in shake flask and pH
      controlled bioreactors. Successful production of heterologous TFH was achieved by
      adapting the original tfh gene to the optimal codon usage of B. megaterium. A
      codon adaption index close to one was reached. The codon optimized tfh was cloned
      into an open reading frame with DNA sequence for the N-terminal signal peptide of
      B. megaterium lipase A and a C-terminal His(6)-tag, all under the control of a
      xylose inducible promoter. Successful TFH production and secretion were observed
      using batch reactor cultivations with complex medium. Expression of the tfh gene
      from the P(xylA) promoter and secretion of produced TFH were compared in detail
      to batch reactor cultivations with semi-defined growth medium. For the first
      time, significant TFH secretion was achieved using a semi-defined medium in
      glucose limited fed batch cultivations yielding 10-fold higher cell densities
      compared to LB medium cultivation. Comparable volumetric TFH activities were
      obtained for both cultivation strategies. Surprisingly, measured specific TFH
      activities exhibited drastic discrepancies between preparations from LB and semi
      defined medium grown B. megaterium. TFH recovery by Ni-chelate affinity
      chromatography resulted in higher purification factors when LB medium was used.
      These results indicated that secreted TFH is favorably produced by batch cultures
      of B. megaterium WH323 in LB medium.

PMID- 16948172
TI  - Efficient regeneration of NADPH using an engineered phosphite dehydrogenase.
AB  - The in situ regeneration of reduced nicotinamide cofactors (NAD(P)H) is necessary
      for practical synthesis of many important chemicals. Here, we report the
      engineering of a highly stable and active mutant phosphite dehydrogenase (12x
      A176R PTDH) from Pseudomonas stutzeri and evaluation of its potential as an
      effective NADPH regeneration system in an enzyme membrane reactor. Two
      practically important enzymatic reactions including xylose reductase-catalyzed
      xylitol synthesis and alcohol dehydrogenase-catalyzed (R)-phenylethanol synthesis
      were used as model systems, and the mutant PTDH was directly compared to the
      commercially available NADP(+)-specific Pseudomonas sp. 101 formate dehydrogenase
      (mut Pse-FDH) that is widely used for NADPH regeneration. In both model
      reactions, the two regeneration enzymes showed similar rates of enzyme activity
      loss; however, the mutant PTDH showed higher substrate conversion and higher
      total turnover numbers for NADP(+) than mut Pse-FDH. The space-time yields of the
      product with the mutant PTDH were also up to fourfold higher than those with mut
      Pse-FDH. In particular, a space-time yield of 230 g L(-1) d(-1) xylitol was
      obtained with the mutant PTDH using a charged nanofiltration membrane,
      representing the highest productivity compared to other existing biological
      processes for xylitol synthesis based on yeast D-xylose converting strains or
      similar in vitro enzyme membrane reactor systems.

PMID- 16948173
TI  - Design and size control of uniform zeolite nanocrystals synthesized in adjustable
      confined voids formed by recyclable monodisperse polymer spheres.

PMID- 16948174
TI  - Polypeptides and 100 years of chemistry of alpha-amino acid N-carboxyanhydrides.
AB  - Syntheses and polymerizations of alpha-amino acid N-carboxyanhydrides (NCAs) were
      reported for the first time by Hermann Leuchs in 1906. Since that time, these
      cyclic and highly reactive amino acid derivatives were used for stepwise peptide
      syntheses but mainly for the formation of polypeptides by ring-opening
      polymerizations. This review summarizes the literature after 1985 and reports on
      new aspects of the polymerization processes, such as the formation of cyclic
      polypeptides or novel organometal catalysts. Polypeptides with various
      architectures, such as diblock, triblock, and multiblock sequences, and star
      shaped or dendritic structures are also mentioned. Furthermore, lyotropic and
      thermotropic liquid-crystalline polypeptides will be discussed and the role of
      polypeptides as drugs or drug carriers are reviewed. Finally, the hypothetical
      role of NCAs in molecular evolution on the prebiotic Earth is discussed.

PMID- 16948176
TI  - Quantitative MRI-pathology correlations of brain white matter lesions developing
      in a non-human primate model of multiple sclerosis.
AB  - Experimental autoimmune encephalomyelitis (EAE) induced with recombinant human
      myelin/oligodendrocyte glycoprotein in the common marmoset is a useful
      preclinical model of multiple sclerosis in which white matter lesions can be well
      visualized with MRI. In this study we characterized lesion progression with
      quantitative in vivo MRI (4.7 T; T(1) relaxation time +/- Gd-DTPA; T(2)
      relaxation time; magnetization transfer ratio, MTR, imaging) and correlated end
      stage MRI presentation with quantitative ex vivo MRI (formaldehyde fixed brains;
      T(1) and T(2) relaxation times; MTR) and histology. The histopathological
      characterization included axonal density measurements and the numeric
      quantification of infiltrated macrophages expressing markers for early active
      [luxol fast blue (LFB) or migration inhibition factor-related protein-14
      positive] or late active/inactive [periodic acid Schiff (PAS) positive]
      demyelinating lesion. MRI experiments were done every two weeks until the monkeys
      were sacrificed with severe EAE-related motor deficits. Compared with the normal
      appearing white matter, lesions showed an initial increase in T(1) relaxation
      times, leakage of Gd-DTPA and decrease in MTR values. The progressive enlargement
      of lesions was associated with stabilized T(1) values, while T(2) initially
      increased and stabilized thereafter and MTR remained decreased. Gd-DTPA leakage
      was highly variable throughout the experiment. MRI characteristics of the cortex
      and (normal appearing) white matter did not change during the experiment. We
      observed that in vivo MTR values correlated positively with the number of early
      active (LFB+) and negatively with late active (PAS+) macrophages. Ex vivo MTR and
      relaxation times correlated positively with the number of PAS-positive
      macrophages. None of the investigated MRI parameters correlated with axonal
      density.

PMID- 16948177
TI  - Bronchiolitis obliterans with organizing pneumonia after rituximab therapy for
      non-Hodgkin's lymphoma.
AB  - Rituximab is a chimeric, anti-CD20 monoclonal antibody initially approved for
      relapsed, refractory indolent B-cell non-Hodgkin's lymphoma (NHL), and is being
      applied in an increasing variety of clinical scenarios. Most adverse events are
      due to an infusion-related symptom complex, and severe pulmonary complications
      are rare. We describe a case of an NHL patient who received rituximab and
      developed symptomatic, biopsy-proven multinodular bronchiolitis obliterans with
      organizing pneumonia (BOOP). This is the first reported case of BOOP associated
      with single-agent rituximab, and along with two other patients we describe, as
      well as two prior reports of BOOP in NHL patients receiving rituximab-based
      combinations, strengthens the possibility of a causal relationship. Moreover,
      these findings suggest that the incidence of BOOP following rituximab therapy may
      be higher than has been previously appreciated. Physicians utilizing rituximab
      should be aware of this association given the difficulty of differentiating
      between presentations of BOOP and neoplastic pulmonary processes.

PMID- 16948181
TI  - Bibliography. Current world literature. The surgical patient.

PMID- 16948182
TI  - Steroid use in liver transplantation: none, perioperative, or full course.

PMID- 16948183
TI  - A new reason for intraoperative blood flow measurement: improving liver allograft
      function.

PMID- 16948184
TI  - Another dendritic cell enters the transplant story.

PMID- 16948185
TI  - Computed tomography for pulmonary embolism.

PMID- 16948186
TI  - Catheters and the treatment of acute lung injury.

PMID- 16948187
TI  - Catheters and the treatment of acute lung injury.

PMID- 16948188
TI  - Caffeine for apnea of prematurity.

PMID- 16948189
TI  - The dilemma of wanting it all.

PMID- 16948190
TI  - Emergency planning is vital.

PMID- 16948191
TI  - Committee service is challenging for public sector.

PMID- 16948192
TI  - Search for the neural correlates of learning to discriminate orientations.

PMID- 16948193
TI  - Growth cone stop signals: inviting to stay or sending away?

PMID- 16948194
TI  - Genomics and the second golden era of cancer drug development.
AB  - The first golden era of cancer drug development was initiated in the 1940s and
      gave rise to the cytotoxic agents that dominate current cancer medicine. The
      second golden era is now underway in which cancer genomics will direct drug
      development.

PMID- 16948195
TI  - [Treatment strategies to slow the progression of chronic renal failure in
      adults].

PMID- 16948199
TI  - Bibliography. Current world literature. Vascular biology.

PMID- 16948200
TI  - [Oral hypoglycemic agents, present and future].

PMID- 16948201
TI  - Lifelong physical activity patterns of sedentary Mexican American women.
AB  - Increasing physical activity, especially for high-risk groups, is a national
      priority; yet little is known about the lifelong patterns of physical activity of
      older Mexican American women. This article describes Mexican American women's
      current sedentary status by reviewing their physical activity history.
      Interventions aimed at promoting health in older adults require an understanding
      of the impact of prior experiences on current health behaviors. Thus, in-depth
      semistructured interviews were conducted with 71 Mexican American women (aged 50
      years or older) recruited from local churches and senior centers. Household,
      occupational, and leisure activities from age 15 years to present time were
      reviewed. A lifelong pattern of low occupational and leisure activity and low to
      moderate household activity were found, with sedentary occupations and no leisure
      activities predominating. Most believed that current household, occupational and
      leisure activities provide enough physical activity, thus influencing
      participation in exercise programs or activities. Attempts to increase physical
      activity for this group need to begin by teaching them age-appropriate and
      culturally acceptable physical activities.

PMID- 16948203
TI  - The ineffectiveness of a non-weight based heparin regimen in achieving
      therapeutic activated partial thromboplastin time (aPTT) in acute coronary
      syndrome.
AB  - Although low molecular weight heparin (LMWH) is increasingly being used in the
      treatment of acute coronary syndrome (ACS), unfractionated intravenous (IV)
      heparin infusion is still widely used in Australian hospitals for the treatment
      of ACS. This paper evaluates the effectiveness of a non-weight based heparin
      regimen in achieving a therapeutic activated partial thromboplastin time (aPTT)
      within 24 hours of IV heparin commencement. A sequential retrospective chart
      review of 99 medical records of ACS patients in a district hospital in south
      western Sydney, Australia, was performed. These patients were prescribed IV
      heparin and did not receive thrombolytic or warfarin therapy. Only 35 per cent
      reached a therapeutic aPTT level within 24 hours of commencement of IV heparin
      therapy. Comparison of therapeutic aPTT and non-therapeutic aPTT groups revealed
      that body weight was the only factor that was significantly different in the two
      groups. Patients who reached the therapeutic aPTT threshold within 24 hours
      weighed significantly less (mean body weight: 70.3 kg versus 80.3 kg) than those
      who did not reach the therapeutic threshold within 24 hours of heparin
      commencement (t = 3.80, d.f. = 86, p < 0.001). Given that a significant
      proportion of patients who require IV heparin therapy exceed the 70 kg body
      weight, the findings from this study suggest that a non-weight based heparin
      regimen is ineffective in the rapid achievement of therapeutic aPTT.

PMID- 16948204
TI  - Non-invasive positive pressure ventilation in acute respiratory failure:
      providing competent care.
AB  - Non-invasive positive pressure ventilation (NPPV) has been used as an alternative
      strategy to provide ventilatory support for patients with acute respiratory
      failure. Most studies demonstrate that the use of NPPV in acute respiratory
      failure results in a reduction in the need for endotracheal intubation and an
      overall survival advantage. However, current evidence, in the form of randomised
      controlled trials, suggests that these benefits may be restricted to patients
      suffering from acute exacerbation of chronic obstructive pulmonary disease
      (COPD). The clinical application of NPPV involves the development of competence
      in delivering the particular intervention. Clinical outcomes and thus valid
      comparisons with alternate methods of ventilatory support can only be made if
      attention is paid to the clinical indications for the application of NPPV and
      patient subgroups it is used to treat and the level of competence of care givers
      in its application and delivery. One essential element of competence is the
      establishment of an appropriate knowledge base and the development of clinical
      practice guidelines. This literature review identifies the current indications
      for NPPV and the relevant information for developing clinical practice guidelines
      for the management of this form of ventilatory support.

PMID- 16948205
TI  - Determinants of critical care nurses' pain management behaviour.
AB  - Research findings over the last 20 years show that critical care nurses (CCNs)
      continue to underestimate and under medicate their patients' pain, despite an
      allegedly strong commitment to pain relief. This literature review investigates
      the determinants of CCNs' pain assessment and management behaviours. Fishbein and
      Ajzen's theory of reasoned action' and Ajzen's theory of planned behaviour have
      been used as models to facilitate understanding of this phenomenon. Fishbein and
      Ajzen highlight attitudes, beliefs, subjective norms and the motivation to comply
      to the anticipated expectations of significant others as the determinants of
      intention to perform behaviour. Attitudinal barriers, knowledge deficits and the
      influence of peers affect CCNs' pain management behaviours, resulting in
      inadequate pain assessment and management practices. CCNs' attitudes about
      narcotic analgesia and how this interacts with gender, age and culture are also
      explored. Through an analysis of the behavioural determinants following the
      models described by Fishbein and Ajzen, strategies can be formulated to address
      CCN deficiencies, improve patient outcomes and satisfaction with nursing care and
      CCN fulfilment. Cervantes was quoted as saying "It's a long way from saying to
      doing". This report aims to improve on this idea.

PMID- 16948206
TI  - Chest x-ray quiz. Pulmonary emphysema.

PMID- 16948207
TI  - Pressure support and elevation following the removal of a radial artery for
      coronary artery bypass grafting.
AB  - The saphenous vein was once the standard coronary artery bypass graft. Alternate
      grafts, primarily the radial artery and the internal mammary artery are now being
      utilised for revascularisation of the heart. However, the radial artery graft
      site can be at risk of oedema and the development of haematoma during the post
      operative period. Also tension on the suture line may compromise circulation and
      create functional problems for the patient. The aim of this study was to assess
      the effect of pressure support (elastic support bandage) and elevation in
      reducing swelling and arm discomfort in the harvest arm. The patients in the
      study undergoing coronary artery bypass grafts were randomly assigned to one of
      three groups: elastic support bandage, collar and cuff sling and elevation on two
      pillows. There were 30 patients in each group. The circumference at three
      locations on the forearm was measured pre-operatively and on post-operative days
      3 and 5. Pain was measured on a visual pain scale, which went from 1-10, with 10
      being the most painful. The patients were also asked whether their arm movement
      felt restricted. The study found that there was no statistically significant
      difference (at the 0.05 level) between the three groups in the amount of swelling
      witnessed at the different forearm locations. There was, however, a significant
      decrease in swelling for all groups between days 3-5, but no difference in pain
      scores between the groups. Moreover, the collar and cuff sling group reported
      movement restriction, which was not apparent in the other two groups. In view of
      the findings, the researchers advocate the elastic support bandage. Patient
      compliance has practical implications when applying treatment and this is
      enhanced by the non cumbersome elastic support bandage. This can be compared to
      the collar and cuff sling and pillow elevation groups where the patient's daily
      activities affects compliance with these two treatments. It is recommended that
      future research be conducted comparing the effects of the elastic support bandage
      with a control group.

PMID- 16948208
TI  - Tilt testing for syncope.
AB  - Vasovagal syncope is a common cause of sudden collapse. It results from
      inappropriate activation of left ventricular mechanoreceptors causing sudden
      vasodilation with bradycardia. Tilt testing is an inexpensive and non-invasive
      way of establishing a vasovagal diagnosis in unexplained syncope. If critical
      care nurses improve their understanding of the pathophysiology of vasovagal
      syncope and the procedure of tilt testing, their care of syncopal patients will
      be enhanced. This literature review discusses the pathophysiology and clinical
      presentation of vasovagal syncope. The procedure of tilt testing is explained and
      the treatment of vasovagal syncope is briefly reviewed.

PMID- 16948209
TI  - [Discussion on the work of Professor J. Fruhling and his excellence as permanent
      Secretary].

PMID- 16948210
TI  - [Lecture by M. A. Burny, President for 2006]].

PMID- 16948211
TI  - [Stories about apothecaries].

PMID- 16948212
TI  - [Effects of environmental pollutants on hormone disturbances].
AB  - There is an increasing scientific concern that organochlorine compounds,
      recognized as environmental pollutants, may cause estrogen-related disorders. One
      of the main hypotheses is that organochlorines can act through their estrogenic
      or anti-estrogenic properties. Many endocrine diseases can be concerned by the
      pathogenic role on environmental residues in their promotion. The carcinogenic
      potential of environmental xenoestrogens on breast cancer is a matter of
      controversy. In Europe, despite their prohibition since the 70's, residues
      persist in soil and rivers, resulting in a widespread contamination of the
      general population. Our results suggest that environmental exposure to p,p'-DDE,
      HCB or PCBS may contribute to multifactorial pathogenesis of breast cancer. Male
      infertility is also a matter of concern. Our data suggest that male infertility
      can be associated with exposure of the mothers to p,p'-DDE, and that deleterious
      effects are probably restricted to intra-uterine life. Early or precocious
      puberty in children adopted from developing countries where organochlorines are
      still used is frequently reported. A possible relationship with exposure to DDT
      is suggested. There are two possible pathways to account for precocious puberty
      following chronic exposure to estrogenic related compounds: weak stimulation of
      estrogen sensitive tissues or removal in Belgium of the suppressing effects of
      estrogens on gonadotrophins, suppressing effect that was due to exposure in the
      origin country.

PMID- 16948213
TI  - [Psychology, psychiatry and oncology: recent and future findings].
AB  - There is an important development of research at the interface of psychology,
      psychiatry and oncology. There are now precise knowledges about assessment and
      type of difficulties experimented by patients and their significant others. The
      content of psychological interventions needed to optimize quality of care is
      starting to be better defined. All this has certainly allowed the development of
      "psycho-oncology" as a new discipline. Our experience at the Jules Bordet
      Institute, Cancer Center of the University of Brussels, will be reported in this
      paper.

PMID- 16948214
TI  - [Complications of central venous and indwelling catheterization].
AB  - Complications on Hickman central venous catheter and venous access ports Hickman
      central venous catheter and venous access ports are widely used in patients with
      hematology or oncology disorders. However, these long-term venous access devices
      can be the source of several kinds of complications that may compromise the
      functional and/or vital patient's prognosis. All these complications must be
      known, diagnosed, treated and prevented. If there is no consensus concerning the
      prevention of catheter-related thrombosis, various methods are now available to
      diagnose, treat and prevent device-related bloodstream infections. Extravasation
      of corrosive drugs represents a very serious complication of long-term venous
      access devices. The surgical technique that uses early subcutaneous wash-out in
      acute extravasation injuries is simple and safe; it helps to reduce the severe
      sequelae of highly toxic drug extravasation for the patient.

PMID- 16948215
TI  - [Multiple sclerosis: the new frontier].

PMID- 16948216
TI  - [Pathology and definition of multiple sclerosis].
AB  - Still today, as for the time of Charcot, multiple sclerosis is defined by
      pathology with the presence of inflammatory demyelinating foci ("plaques")
      disseminated in the white matter of the central nervous system (CNS). Each lesion
      follows its genuine course with an acute formation followed by a more or less
      complete regression whereas new lesions are forming elsewhere in the CNS
      throughout the disease duration. A permanent dynamics of the inflammatory
      activity, substratum of the lesional "dissemination in space and time"
      characteristic of the disease, is therefore operating. During the relapsing
      remitting phase, focal lesions are at the forefront of the pathological
      abnormalities. During the progressive phase, be it secondary or primary,
      macroscopic atrophy and axonal loss, the main explanation of the irreversible
      neurological disability and the expression of the diffuse, chronic and
      progressive degeneration of the CNS, are emerging to the first place. Persisting
      controversies are many. Are there several distinct immunohistopathological
      patterns of the disease or do they correspond to different moments of the same
      disease? Is there a continuum between classic MS and pathological variants such
      as Marburg's disease, Balo's concentric sclerosis, Schilder's disease, and
      Devic's acute neuromyelitis optica or are there distinct nosological entities? As
      for autoimmunisation which leads to the selective destruction of myelin, is it
      primary or secondary to an oligodendrocytic apoptotic process?

PMID- 16948217
TI  - [Pathophysiology of multiple sclerosis].
AB  - Patients with multiple sclerosis (MS) can exhibit an exceptionally wide variety
      of symptoms. This is largely due to the semi-random distribution of the lesions
      in the central nervous system (CNS). Most lesions occur in apparently "silent"
      areas in the brain, and so cause no detectable symptoms. The disease is therefore
      much more active than a mere clinical monitoring would suggest. Most symptoms are
      related to a loss of function. During the relapses, this is due to a failure of
      axonal conduction at the site of the lesion(s). The conduction block is caused by
      the local demyelination which prevents the saltatory conduction but also
      seemingly, to some extend, by the inflammation per se. Remissions are related to
      a recovery of function of the affected axons owing to a spreading of sodium
      channels along the demyelinated axolemma but also to cerebral functional
      plasticity and remyelination. However, nerve conduction remains slower and less
      secure than normal, easily altered by physico-chemical changes such as the
      increase in body temperature (Uhthoff's phenomenon). Remission is incomplete when
      the lesion has led to axonal transaction and therefore axonal loss. Progression
      in MS is mainly related to "slow-burning" diffuse and chronic axonal loss in a
      toxic inflammatory milieu. Lastly, some symptoms in MS are so-called "positive"
      arising from an acquired hyperexcitability of demyelinated axons and occur either
      spontaneously (e.g. paresthesias) or mechanically (e.g. Lhermitte's sign).

PMID- 16948218
TI  - [Etiology of multiple sclerosis].
AB  - Multiple sclerosis is an inflammatory disease of the central nervous system
      responsible for demyelinating lesions within white matter in young adults. The
      activation of autoreactive CD4+ but also CD8+ T cells directed against myelin
      antigens of the central nervous system is a key phenomenon at the origin of
      multiple sclerosis lesions. Its etiology is unknown but implies the existence of
      genetic traits and a triggering by environmental factors such as viral
      infections. However, no virus or other environmental factor has been directly
      involved in the triggering of the disease. Functionnal abnormalities on
      regulation systems of immunity, such as regulatory T cells, could be partially
      involved in the triggering of the disease. However, it appears, on the basis of
      recent findings, that multiple sclerosis is not only a disease of the immune
      system but also implies specific neurobiological factors which must be determined
      in studies to come.

PMID- 16948219
TI  - [The natural history of multiple sclerosis].
AB  - The course of multiple sclerosis (MS) results from the interplay of two clinical
      processes, relapses and progression. Three main clinical forms may be identified
      as relapsing-remitting, secondary progressive and primary progressive. The
      disease appears on average at the age of 30 and follows a remitting or a
      progressive course in 85% and 15% of the cases, respectively. Initial symptoms
      are related to an isolated or combined disturbance(s) of the long tracts of the
      central nervous system, of the brainstem, or of the optic nerve in 70%, 20% and
      25% of the cases, respectively. The relapse rate is one relapse on average every
      other year. After an exacerbating-remitting onset of MS, secondary progression
      appears after 19 years on average. The median time to reach the landmarks of
      irreversible disability are 8 years regarding limitation of ambulation, 20 years
      for walking with a stick, and 30 years for wheel-chair dependency. In fact, MS
      prognosis is highly variable depending on individuals. All the intermediate types
      do exist between malignant forms, possibly lethal, and benign forms (circa 30% of
      the cases) that allow normal daily life. The clinical and paraclinical predictive
      factors identified so far have been acknowledged statistically. They provide
      little help however, if any, when an individual is concerned. Recent research has
      showed that relapses have only a marginal effect, relatively to progression, on
      the accumulation of irreversible neurological disability. Furthermore, the age
      when reaching the landmarks of irreversible disability is essentially similar
      whatever the mode of onset of MS, be it exacerbating-remitting or progressive. In
      spite of the outstanding clinical polymorphism of MS, a unifying concept of the
      disease ("complexity vs heterogeneity") can be put forward.

PMID- 16948221
TI  - [Contribution of nuclear magnetic resonance imaging in multiple sclerosis].
AB  - Conventional MRI has become essential in the field of multiple sclerosis (MS). It
      reveals brain injury in visualising focal lesions of demyelination of the white
      matter, damage of the blood-brain barrier, and tissue loss within the lesions.
      These parameters are now used for an early diagnosis and for assessing the
      efficacy of new therapies. For years, neuroimaging research groups have been
      developing MRI techniques to get more sensitive and specific parameters of brain
      injury. Such techniques provide information on the extent of atrophy (volume,
      brain thickness), the metabolism (MR spectroscopy), the tissue structure
      (magnetization transfer and diffusion) and the compensation processes (functional
      MRI) of the brain. They lead to new approaches for analysing the
      pathophysiological processes at work in MS and their course in time.

PMID- 16948220
TI  - [Multiple sclerosis: positive diagnosis].
AB  - The diagnosis of multiple sclerosis (MS) is based on the dissemination in time
      and space of inflammatory central nervous system episodes. The recently proposed
      criteria for MS include MRI data as a possible definition of this dissemination.
      These new criteria make possible a very early diagnosis of MS.

PMID- 16948222
TI  - [Drug therapy in multiple sclerosis].
AB  - For the last 10 years, three disease-modifying-therapy drugs have been approved
      by the French health authorities for the treatment of relapsing-remitting MS: two
      of them are immunomodulatory agents (interferon beta 1a or 1b and glatiramer
      acetate), administered by subcutaneous or intramuscular injections at different
      time points, reducing by about 30% the risk of relapses. The third drug approved
      is an immunosuppressive agent, mitoxantrone, administered intravenously at a dose
      of 12 mg/m2 per month up to a maximum cumulative dose of 72 mg/m2, used as a
      second line therapy in rapidly worsening relapsing MS non responder to
      immunomodulatory agents. The impact of such medications in MS patients with
      gradual progression of disability has not yet been established either in
      secondary or primary progressive MS.

PMID- 16948223
TI  - [Therapeutic perspectives in multiple sclerosis].
AB  - Although consistent progress has been made over the last decade in the treatment
      of the inflammatory component of multiple sclerosis, these strategies have only
      partial efficacy. Numerous innovative therapeutic perspectives are emerging:
      currently, monoclonal antibody induced inhibition of entry of activated
      lymphocytes into the central nervous system is promising, but the benefit/risk
      ratio has still to be evaluated. In parallel, combination strategies with
      immunomodulators and/or immunosuppressants, and specific immunotherapy are
      investigated. In addition, in the longer-term, there is active development of
      experimental strategies aimed at repairing damaged tissue--both axon and myelin.
      These strategies are still at the preclinical stage. Therapeutic optimisation may
      come from an association between anti-inflammatory treatments acting upstream on
      the immune response, and neuroprotective and myelin repair strategies acting
      downstream, directed at the lesions.

PMID- 16948224
TI  - [Multiple sclerosis in MEDLINE].

PMID- 16948225
TI  - [Pregnancy and multiple sclerosis].

PMID- 16948226
TI  - [Holiday duties].

PMID- 16948227
TI  - [Problems posed by genetic diseases: trisomy 21].

PMID- 16948228
TI  - [Acute soft tissue infections].

PMID- 16948229
TI  - [Hypothyroidism in adults].

PMID- 16948230
TI  - [Malaria].

PMID- 16948231
TI  - [Napoleon. Autopsy of an autopsy].

PMID- 16948232
TI  - [A young woman with a labile mood, hyperactivity, hyperthermia and exhaustion:
      symptoms of lethal catatonia].
AB  - A 22-year-old woman went through a period with a labile mood that first turned
      into psychotic hyperactivity and was then followed by hyperthermia and
      exhaustion. This was accompanied by diminished consciousness, sinus arrhythmia
      and respiratory insufficiency. With a working diagnosis of 'lethal catatonia' she
      was treated by electroshock and later also with the antipsychotic agent
      quetiapine. After a few electroshock treatments her vital functions improved and
      ultimately, the patient recovered. Lethal catatonia is characterised by acute
      excitation, catalepsy, autonomic instability and fever, which can lead to death.
      The syndrome often starts with mood instability, which turns into hyperactivity
      accompanied by hyperthermia and exhaustion. The creatine kinase, blood
      sedimentation rate and leukocyte count are often raised. Lethal catatonia must be
      distinguished from the neuroleptic malignant syndrome, serotonin syndrome and
      encephalitis. The pathophysiology is unclear, but most reports suggest a
      hypodopaminergic state. The syndrome is associated with affective disorders and
      schizophrenia. Early recognition is made difficult by the low frequency of
      appearance, diversity in nomenclature, and strong resemblance to other syndromes.

PMID- 16948233
TI  - [MRI-guided biopsy of the breast: new possibilities but also new problems].
AB  - The use of MRI in the detection and management of breast cancer is increasing.
      Because of its relatively low specificity, many patients turn out in retrospect
      to have a false-positive biopsy. Conversely, due to the shortcomings of available
      biopsy techniques, breast cancer can also be missed and left behind in the
      breast. The introduction of MRI of the breast in daily practice may therefore
      have a great psychological impact on the group of mostly young patients who are
      offered this diagnostic modality because of their familial risk. In order to
      prevent learning curves in every clinic where MRI screening is implemented, the
      management of this special group should be concentrated in centres with broad
      experience in the treatment of patients with a genetic predisposition for breast
      cancer.

PMID- 16948234
TI  - [Echo-guided compression sclerotherapy using foam: an improvement in the
      treatment of varicose veins].
AB  - Recently, echo-guided compression sclerotherapy (ECST) using foam was introduced
      as an efficient and patient-friendly therapy for the treatment of varicose veins.
      ECST enables operation under either spinal or general anaesthetic to be avoided.
      Foam for phlebological use is a volatile mixture of a gas, usually air, and a
      small quantity of liquid with the characteristics of a detergent or soap, such as
      polidocanol. The product that is injected has deterging properties. It reduces
      the surface tension of endothelial cells resulting in the destruction of the
      vascular wall. The treated vessel is subsequently reduced to a fibrous cord. For
      small calibre varicose veins, sclerosing fluids are used. In The Netherlands,
      until relatively recently branch varicosities of the long and short saphenous
      veins were treated surgically, but ECST using foam can be successfully used to
      treat wide calibre varicosities. Caution is advised in treating patients who are
      known to have a history of open foramen ovale because of the higher risk of the
      occurrence of scotoma and transient cerebral ischaemia.

PMID- 16948235
TI  - [The Dutch Child Health Care guideline 'early detection of congenital heart
      disease in the age group 0-19 years'].
AB  - The Dutch Child Health Care guideline on the early detection of congenital heart
      disease was developed according to the principles for evidence-based guideline
      development and contains recommendations for the conduct of the examination
      during routine check-ups and for referral criteria. Most congenital heart
      diseases can be detected in the first year of life if physicians and nurses work
      according to this guideline. Important early times for screening are the home
      visit to infants at the age of two weeks by the child health nurse and the
      routine check-up of infants at the age of four weeks by the child health care
      physician. A routine cardiac screening is carried out in every child by the nurse
      and the physician at times specified in the basic list of professional
      responsibilities. A more extensive examination is carried out when indicated.
      Routine cardiac check-ups are recommended until the age of four, after which they
      should be done only when indicated on medical grounds. A feasibility study showed
      that physicians and nurses can apply the guideline effectively, provided that
      they take part in prior specific training.

PMID- 16948236
TI  - [Research sponsored by the industry benefits scientific progress].
AB  - The conflicts of interest dominate discussions on collaborative research between
      academic institutions and the pharmaceutical industry. Although one should not be
      blind to such possibilities and remain critical, the advantages outweigh the
      risks by far. The remaining diseases for which adequate pharmacotherapy is
      lacking are complex and require an expensive research infrastructure. Therefore,
      progress will benefit from collaboration and should not be hindered by short
      sightedness.

PMID- 16948237
TI  - [Sponsoring of research by the industry is not good for science].
AB  - The pharmaceutical industry is not basically interested in knowledge about
      diseases and their treatment--its main interest is selling drugs. Hence, its
      research may even be aimed at shifting the border between health and disease in
      order to produce more indications for which drugs can be prescribed. In contrast,
      non-industry sponsored research can be aimed at solving medical problems that
      really matter and problems for which other forms of treatment are indicated than
      medication. Therefore, industry-sponsored research is bad for medical science.

PMID- 16948238
TI  - [Diagnostic image (286). A man with a painful axilla].
AB  - A 61-year-old left-handed tennis player suffered dislocation of his implanted
      defibrillator, which was protruding through a left axillary skin rip.

PMID- 16948239
TI  - [Diagnostic value of patient history and physical examination in elderly patients
      with urinary incontinence; a literature review].
AB  - OBJECTIVE: To assess the validity of patient history and physical examination in
      elderly patients in the diagnosis ofvarious types of urinary incontinence.
      DESIGN: Literature review. METHOD: Articles on the diagnosis of urinary
      incontinence in elderly patients (patient history and/or physical examination
      versus urodynamic testing) were identified using PubMed, Picarta (a Dutch
      database) and the reference lists of the articles found. Articles were published
      between January 1970 and August 2005. The applicability and quality of the
      articles were assessed using the relevant Cochrane criteria. 'Sufficient
      diagnostic evidence' was defined as a positive likelihood ratio > 5 and a
      negative likelihood ratio < 0.02. RESULTS: 5 studies met the eligibility
      criteria; 4 were performed in the second-line setting and 1 in a general
      population. All 5 studies involved women aged 55 years or older. None of the 5
      studies found a positive or negative likelihood ratio for providing sufficient
      diagnostic evidence for various types of urinary incontinence. In the study
      conducted in a general population, the positive and negative likelihood ratios
      for the presence of stress incontinence according to patient history and physical
      examination were 3.23 and 0.40, respectively. CONCLUSION: Few adequate studies
      have been reported on the validity of clinical evaluation in the diagnosis of
      urinary incontinence in older women, and no studies have been conducted in men.
      The validity of clinical evaluation has been demonstrated only in the diagnosis
      of stress incontinence in older women.

PMID- 16948240
TI  - [Occult gastrointestinal bleeding due to a Dieulafoy lesion in the terminal
      ileum].
AB  - A 50-year-old man awaiting liver transplantation for primary sclerosing
      cholangitis developed iron-deficiency anaemia. Repeated occult gastrointestinal
      bleeding led to an increasing need for blood transfusions. After multiple
      oesophagogastroduodenoscopies and colonoscopies, videocapsule endoscopy finally
      demonstrated a polyp-like lesion in the terminal ileum. The lesion had not been
      detected despite two attempts (oral and anal) at double-balloon enteroscopy and
      even a peroperative enteroscopy. Only during a second laparotomy, again involving
      peroperative enteroscopy, a small red lesion was detected and resected 80 cm
      proximal to the ileocecal valve (Bauhin's valve). Histology revealed a Dieulafoy
      lesion. Four months later, after normalisation and stabilisation of his
      haemoglobin level, the patient received a successful liver transplant. If the
      cause of occult gastrointestinal bleeding in a patient remains unclear despite
      regular endoscopic procedures, new techniques like videocapsule endoscopy and
      double-balloon enteroscopy may contribute to identifying the cause. This may lead
      to an exceptional finding such as a Dieulafoy lesion in the distal ileum.

PMID- 16948241
TI  - [MRI-guided biopsy of suspicious abnormalities in the breast].
AB  - In a 55-year-old woman, an echographically occult breast tumour was only visible
      in one direction on mammography. MRI-guided needle localisation of the lesion
      followed by surgical excision biopsy were then carried out for diagnostic
      purposes. In a second woman, 61 years of age, mammographic needle localisation of
      a deep, echographically occult, lesion was unsuccessful. She then also underwent
      MRI-guided needle localisation followed by surgical excision biopsy. A third
      woman, also 61 years of age, with known carcinoma underwent an MRI staging study.
      This revealed a second, mammographically and echographically occult, lesion for
      which MRI-guided large-core needle biopsy was done. MRI of the breast has a high
      sensitivity for the detection of invasive breast carcinoma. MRI of the breast
      reveals suspicious lesions that cannot be seen on the conventional mammogram or
      by echography in 15-25% of the cases. In order to obtain tissue from these
      lesions for histopathology, MRI-guided biopsy techniques have been developed. The
      most commonly used methods are MRI-guided needle localisation followed by
      surgical excision biopsy and MRI-guided large-core needle biopsy. The demand for
      MRI-guided breast interventions is growing because of the increasing use of MRI
      of the breast in clinical practice.

PMID- 16948242
TI  - [Worldwide changes in the environment and public health].
AB  - In recent years, there is a growing awareness that, as a result of human
      activities, large-scale environmental changes are occurring with resultant risks
      for human health. The most important of these are changes in climate and other
      aspects of the atmosphere, in land use and soil erosion, in the use and
      contamination of fresh water, and in biodiversity. The usual estimates of the
      health-related effects of environmental problems in The Netherlands ignore the
      current effects of global environmental changes outside the borders of The
      Netherlands, as well as the possible future effects of these changes in The
      Netherlands. It would be irresponsible to allow ourselves to be put at ease by
      these estimates. Health-care institutions are co-responsible for an adequate
      response to global environmental changes, not only because health care as such
      also contributes to environmental damage but also because medical and health
      related research can help to further our understanding of the nature of these
      health risks and the possible countermeasures.

PMID- 16948243
TI  - [The village healer].

PMID- 16948244
TI  - [A multidisciplinary approach is necessary in the neonatal withdrawal syndrome].

PMID- 16948245
TI  - [Fever and exanthema as manifestations of the second stage of syphilis].

PMID- 16948246
TI  - Stopping internet-based tobacco sales through domain name seizure.

PMID- 16948247
TI  - U.S. physicians disciplined for criminal activity.

PMID- 16948248
TI  - Liability, regulation and policy in surgical innovation: the cutting edge of
      research and therapy.

PMID- 16948249
TI  - The future of telemedicine & its Faustian reliance on regulatory trade barriers
      for protection.

PMID- 16948250
TI  - Cock-a-doodle-doo: pandemic avian influenza and the legal preparation and
      consequences of an H5N1 influenza outbreak.

PMID- 16948251
TI  - Biblical biopolitics: judicial process, religious rhetoric, Terri Schiavo and
      beyond.

PMID- 16948252
TI  - In respect of people living in a permanent vegetative state--and allowing them to
      die.

PMID- 16948253
TI  - An economic assessment of damage caps in medical malpractice litigation imposed
      by state laws and the implications for federal policy and law.

PMID- 16948254
TI  - A right to no meaningful review under the due process clause: the aftermath of
      judicial deference to the federal administrative agencies.

PMID- 16948255
TI  - Schroeder Lecture. Worst pills, best pills.

PMID- 16948256
TI  - Truth in testing laws: a shot in the arm for designer gene tests.

PMID- 16948257
TI  - [Detection of drug transport using X-ray techniques].
AB  - The purpose of the paper was to show X-ray techniques used to discover drugs
      transported inside the body (body packers), on the body surface, in the garments
      or luggage, in goods and vehicles. The analysis was based on the X-ray findings
      of 141 body packers caught in Hamburg between 1989 and 2004 as well as individual
      cases from personal collections. The use of X-rays for border and security checks
      is described, different technical concepts are demonstrated and examples are
      given, e. g. transmission (fluoroscopic) and backscatter imaging of humans,
      luggage, goods, and vehicles as well as X-ray spectroscopy. The results showed
      that body packers produce characteristic findings in native X-ray photographs,
      which are even more pronounced in CT scans and after application of contrast
      media. Backscatter imaging allows the investigation of the body surface and the
      clothing. Transmission and backscatter imaging is suitable for checking humans,
      goods, passenger cars, trucks and containers. With the help of X-ray spectroscopy
      suspicious substances can be identified without opening the packaging material.
      According to present findings, the radiation dose applied seems low compared with
      exposure to environmental radiation and cosmic radiation during flights. The
      pictures obtained with the backscatter technique show the person checked in the
      nude, which raises the question of privacy versus the right of the state to carry
      out inspections and controls.

PMID- 16948258
TI  - [Morphology of bullet wounds when using police ammunition, type QD-P.E.P].
AB  - 6 years after introduction of the police ammunition QD-P.E.P. (9 mm caliber), 9
      bullet wounds are presented from forensic investigations along with the results
      of experimental shots at pig carcasses. The evaluation reveals the characteristic
      pattern of such bullet wounds: a skin defect which is almost as large as the
      caliber and has a sharp-edged border thus looking like it has been punched out;
      the contusion ring ("abrasion ring") is conspicuously narrow. These findings can
      be explained by the shape and design of the projectile. In regular police work
      immediate incapacitation has not always been achieved, depending on the entry
      location of the bullet. Experimental shots at pig carcasses showed that in the
      case of shots at extremities, the residual energy of the exiting bullet may be
      sufficient to generate another penetrating bullet wound.

PMID- 16948259
TI  - [Atypical "body packing syndrome"--a case report].
AB  - A case of ingested cocaine is reported in which death must be classified as body
      packer syndrome although both the temporal relationship and the number of packets
      were atypical. The deceased, a consumer of hard drugs who smuggled for his own
      use, was found in his flat. He was resuscitated and survived for another four
      days in hospital. Only four intact drug packages were found in the upper gastro
      intestinal tract. The concentrations of cocaine in blood and organs were
      relatively low but in a potentially lethal range. The case is presented, and its
      particularities as well as the option of induced vomiting as a way of preventing
      the fatal outcome are discussed.

PMID- 16948260
TI  - [Problems of assessing sibship probabilities by means of genetic analysis].
AB  - Nowadays, kinship studies based only on STR analysis are a very common practice.
      Apart from regular paternity cases, there is a rising number of cases in which
      the type of sibship between two persons has to be determined. Very often the
      parents or further relatives are unavailable for testing, so that the probability
      e. g. for a half-sibship has to be calculated as a deficiency situation. 50
      unrelated persons (Group 1), 50 full siblings (Group 2), and 50 half-siblings
      (Group 3) were genotyped using the 15 STRs comprised by the AmpFlSTR Identifiler
      multiplex PCR-kit to investigate the reliability of common statistics programs
      and the indicative value of the calculated probabilities. Using a commercially
      available statistics program, we calculated probabilities for the following
      hypotheses: 1. The persons investigated are full siblings; 2. the persons
      investigated are half-siblings; 3. the persons investigated are unrelated. After
      STR analysis, half-sibling probabilities between 0.03 %-97.56% for group 1,
      between 0.01%-78.46% for group 2, and between 24.28%-90.18% for group 3 were
      calculated. In addition, the authors present two complicated deficiency cases
      which could be resolved only by extensive DNA typing using X- and Y-chromosomal
      loci, respectively, as well as the investigation of further relatives. The
      results of this study suggest that typing of autosomal STRs alone is no
      sufficient tool for resolving cases of possible half-sibship, even if
      probabilities of more than 90.0% are obtained. Due to the results of our study we
      suggest the implementation of mandatory standards for the investigation and
      interpretation of complicated kinship cases.

PMID- 16948264
TI  - Independent nurse consultant.

PMID- 16948262
TI  - Oklahoma Nurses Association 2006 Annual Legislative Report.

PMID- 16948265
TI  - Another agent of bio-terrorism: tularemia.

PMID- 16948266
TI  - Understanding pandemic influenza.

PMID- 16948267
TI  - [Hygiene and other virtues].

PMID- 16948268
TI  - ["Bad news" for nosocomial infections].

PMID- 16948269
TI  - [Important role of hygiene counselors].

PMID- 16948270
TI  - [From surgical procedures to stitches].

PMID- 16948271
TI  - [German Nursing Societies takes the future in hand].

PMID- 16948272
TI  - ["This career was very good to me"].

PMID- 16948274
TI  - [End of the line].

PMID- 16948273
TI  - [Regrets that nurses do not have more importance].

PMID- 16948275
TI  - ["Politics directly affect everyday nursing"].

PMID- 16948276
TI  - [Pain scales for infants and small children].

PMID- 16948277
TI  - [Involvement without measuring].

PMID- 16948278
TI  - [A partnership rich in discoveries].

PMID- 16948279
TI  - [A well-oriented patient is better cared for].

PMID- 16948280
TI  - [Better utilization of movement].

PMID- 16948281
TI  - [A mission to change representation].

PMID- 16948282
TI  - [The future is well in hand].

PMID- 16948283
TI  - [Story of a long gestation].

PMID- 16948284
TI  - ["I am fascinated by the richness of uninterrupted nurses"].

PMID- 16948285
TI  - [Handwashing].

PMID- 16948286
TI  - Information and service needs of persons with Alzheimer's disease and their
      family caregivers living in rural communities.
AB  - This study aimed to identify the information and service needs of persons with
      Alzheimer's disease (AD) and their family caregivers living in rural communities
      and to assess differences and similarities in each partner's perspective. In an
      outpatient clinic setting, a self-report survey was completed by 100 caregivers,
      while a similar survey was used to interview 100 persons with mild to moderate
      AD. The survey assessed respondents' interest in information or services related
      to 22 topics about AD and various aspects of coping with the disease. Although
      more caregivers than persons with AD reported interest in each topic, 8 of the
      top 10 topics endorsed by each group of respondents were the same. However,
      analysis of responses by dyads revealed substantial disagreement in terms of each
      partner's interest in information and services. Patient and family education, as
      well as referrals for services, must take into account each partner's unique
      perspective and needs.

PMID- 16948287
TI  - Developing more flexible approaches to respite for people living with dementia
      and their carers.
AB  - A vital aspect of the care of people living with dementia is the provision of
      respite services, which allow family caregivers a break from the caring role. The
      flexibility of such services has consistently been identified as a major factor
      in whether families make use of them. This study of dementia respite services
      explores the notion of flexibility and then presents a comprehensive checklist
      that respite service providers can use to assess the flexibility of their
      service. It then provides brief descriptions of a number of creative respite
      programs that are examples of flexible service provision.

PMID- 16948288
TI  - Insight and cognitive impairment: effects on quality-of-life reports from mild
      cognitive impairment and Alzheimer's disease patients.
AB  - This study follows previous work to determine the effect of patient insight and
      cognitive impairment on the reliability and validity of self-reported quality of
      life (QOL) from patients diagnosed with Alzheimer's disease (AD) and mild
      cognitive impairment (MCI). AD and MCI patients (N = 68) and their caregivers
      participated. Patients with impaired insight provided QOL ratings that were less
      reliable than those provided by patients with better insight. Patient-caregiver
      agreement for. QOL reports was used as an index of validity. Neither better
      insight nor lesser cognitive impairment suggested better agreement. Thus, even
      when patient insight is intact, patient reports are unlikely to agree with
      caregiver reports. Patient and caregiver reports about patient QOL may represent
      2 unique, yet potentially valid, perspectives.

PMID- 16948289
TI  - Development and testing of a new outcome measure of relationship between patients
      with Alzheimer's disease and their partners.
AB  - In mild Alzheimer's disease (AD), loss of relationship with the patient is a
      significant consequence for the partner (relative) and may be amenable to
      improvement with effective intervention. To evaluate relationship dynamics, the
      authors developed and tested content and discriminative validity of the self
      administered Partner-Patient Questionnaire for Shared Activities among 100
      partners of patients with mild to moderate Alzheimer's disease. Principal
      component analysis confirmed that interference in 17 activities derived from the
      literature and partner-specified activities comprised a relationship factor;
      internal consistency was very high. Time spent caregiving, caregiver esteem, lack
      of family support, and impact on partner health and activities were significant
      predictors of the Partner-Patient Questionnaire for Shared Activities, but the
      patient's cognitive and mood states were not. The Partner-Patient Questionnaire
      for Shared Activities warrants additional psychometric testing as a measure of
      Alzheimer's disease outcome.

PMID- 16948290
TI  - Systemic inflammatory markers and risk of dementia.
AB  - Inflammation plays an important role in the pathogenesis of Alzheimer's disease.
      This article reviews the results of prospective studies demonstrating that the
      level of systemic inflammation markers, particularly C-reactive protein and
      interleukin-6, can predict cognitive decline or dementia. The potential
      mechanisms linking systemic inflammatory molecules to cognitive decline are also
      discussed.

PMID- 16948291
TI  - Neuropsychiatric and behavioral symptoms in a community sample of Hispanics with
      Alzheimer's disease.
AB  - The purpose of this study was to characterize and compare neuropsychiatric
      symptoms in a sample of 367 community-dwelling subjects: 70 Hispanics and 230 non
      Hispanic white patients with Alzheimer's disease, and 22 Hispanics and 45 non
      Hispanic white healthy age-matched controls. Neuropsychiatric symptoms were
      common among all patients with Alzheimer's disease. In the Alzheimer's disease
      groups, Hispanic subjects presented to the initial assessment with more symptoms
      than non-Hispanic white subjects did. In comparison to the non-Hispanic white
      population, the proportion of Hispanics with neuropsychiatric and behavioral
      symptoms was higher. These findings have implications for differential
      sociocultural presentations of Alzheimer's disease among ethnic/racial groups.

PMID- 16948292
TI  - Correlations between the Functional-Cognitive Assessment Scale and the
      Alzheimer's Disease Assessment Scale when administered to patients with dementia
      residing in long-term care.
AB  - The Alzheimer Disease Assessment Scale (ADAS) and the Functional Cognitive
      Assessment Scale (FUCAS) examine the cognitive performance of patients with
      dementia. ADAS has been widely used as a clinical instrument, mainly in clinical
      trials. FUCAS is a useful tool in diagnosing early dementia since it examines
      executive skills. Moreover, it is sensitive to the subtle changes that occur
      during the progress of the disease. The aim of this study was to examine the
      possible correlations between FUCAS and ADAS. The 2 neuropsychological scales
      were administered to 32 patients with dementia residing in long-term care. They
      were 12 men and 20 women, 65 to 90 years old, with 4 to 12 years of education.
      Twenty-four patients were reassessed 3 months after the first assessment, with
      the same scales. Pearson's correlation showed that the total score of FUCAS
      correlated significantly with the total score of ADAS: r = 0.80 (P < .01). The t
      test showed that changes over the 3 months for FUCAS were more significant than
      ADAS, suggesting that FUCAS is a more sensitive tool.

PMID- 16948293
TI  - Frontotemporal dementia-like phenotypes associated with presenilin-1 mutations.
AB  - Frontal behavioral changes may be the presenting features of single-photon
      emission tomography (presenilin-1 [PS-1]) mutations, the most common cause of
      familial Alzheimer's disease (AD). The authors describe a PS-1 (M233L) mutation
      with the features of frontotemporal dementia (FTD) and review the literature. PS
      1 mutations may produce FTD-like phenotypes with the neuropathology of AD. Some
      PS-1 mutations have additional Pick's bodies, a neuropathological marker of FTD,
      and a report of a PS-1 (G183V) mutation found Pick's bodies without amyloid
      plaques. The patient and the literature suggest that PS-1 mutations result in an
      overlapping continuum of the clinical and neuropathological features of AD and
      FTD. In PS-1 mutations, the expression of AD or FTD may depend on the degree of
      loss of function of the PS-1 gene and the resultant tau pathophysiology.

PMID- 16948294
TI  - Tri-focal tensor-based multiple video synchronization with subframe optimization.
AB  - In this paper, we present a novel method for synchronizing multiple (more than
      two) uncalibrated video sequences recording the same event by free-moving full
      perspective cameras. Unlike previous synchronization methods, our method takes
      advantage of tri-view geometry constraints instead of the commonly used two-view
      one for their better performance in measuring geometric alignment when video
      frames are synchronized. In particular, the tri-ocular geometric constraint of
      point/line features, which is evaluated by tri-focal transfer, is enforced when
      building the timeline maps for sequences to be synchronized. A hierarchical
      approach is used to reduce the computational complexity. To achieve subframe
      synchronization accuracy, the Levenberg-Marquardt method-based optimization is
      performed. The experimental results on several synthetic and real video datasets
      demonstrate the effectiveness and robustness of our method over previous methods
      in synchronizing full-perspective videos.

PMID- 16948295
TI  - Gabor-based kernel PCA with doubly nonlinear mapping for face recognition with a
      single face image.
AB  - In this paper, a novel Gabor-based kernel principal component analysis (PCA) with
      doubly nonlinear mapping is proposed for human face recognition. In our approach,
      the Gabor wavelets are used to extract facial features, then a doubly nonlinear
      mapping kernel PCA (DKPCA) is proposed to perform feature transformation and face
      recognition. The conventional kernel PCA nonlinearly maps an input image into a
      high-dimensional feature space in order to make the mapped features linearly
      separable. However, this method does not consider the structural characteristics
      of the face images, and it is difficult to determine which nonlinear mapping is
      more effective for face recognition. In this paper, a new method of nonlinear
      mapping, which is performed in the original feature space, is defined. The
      proposed nonlinear mapping not only considers the statistical property of the
      input features, but also adopts an eigenmask to emphasize those important facial
      feature points. Therefore, after this mapping, the transformed features have a
      higher discriminating power, and the relative importance of the features adapts
      to the spatial importance of the face images. This new nonlinear mapping is
      combined with the conventional kernel PCA to be called "doubly" nonlinear mapping
      kernel PCA. The proposed algorithm is evaluated based on the Yale database, the
      AR database, the ORL database and the YaleB database by using different face
      recognition methods such as PCA, Gabor wavelets plus PCA, and Gabor wavelets plus
      kernel PCA with fractional power polynomial models. Experiments show that
      consistent and promising results are obtained.

PMID- 16948296
TI  - Effective palette indexing for image compression using self-organization of
      Kohonen feature map.
AB  - The process of limited-color image compression usually involves color
      quantization followed by palette re-indexing. Palette re-indexing could improve
      the compression of color-indexed images, but it is still complicated and consumes
      extra time. Making use of the topology-preserving property of self-organizing
      Kohonen feature map, we can generate a fairly good color index table to achieve
      both high image quality and high compression, without re-indexing. Promising
      experiment results will be presented.

PMID- 16948297
TI  - Wavelet-based scalable L-infinity-oriented compression.
AB  - Among the different classes of coding techniques proposed in literature,
      predictive schemes have proven their outstanding performance in near-lossless
      compression. However, these schemes are incapable of providing embedded
      L(infinity)-oriented compression, or, at most, provide a very limited number of
      potential L(infinity) bit-stream truncation points. We propose a new
      multidimensional wavelet-based L(infinity)-constrained scalable coding framework
      that generates a fully embedded L(infinity)-oriented bit stream and that retains
      the coding performance and all the scalability options of state-of-the-art L2
      oriented wavelet codecs. Moreover, our codec instantiation of the proposed
      framework clearly outperforms JPEG2000 in L(infinity) coding sense.

PMID- 16948298
TI  - Adaptive downsampling to improve image compression at low bit rates.
AB  - At low bit rates, better coding quality can be achieved by downsampling the image
      prior to compression and estimating the missing portion after decompression. This
      paper presents a new algorithm in such a paradigm, based on the adaptive decision
      of appropriate downsampling directions/ratios and quantization steps, in order to
      achieve higher coding quality with low bit rates with the consideration of local
      visual significance. The full-resolution image can be restored from the DCT
      coefficients of the downsampled pixels so that the spatial interpolation required
      otherwise is avoided. The proposed algorithm significantly raises the critical
      bit rate to approximately 1.2 bpp, from 0.15-0.41 bpp in the existing downsample
      prior-to-JPEG schemes and, therefore, outperforms the standard JPEG method in a
      much wider bit-rate scope. The experiments have demonstrated better PSNR
      improvement over the existing techniques before the critical bit rate. In
      addition, the adaptive mode decision not only makes the critical bit rate less
      image-independent, but also automates the switching coders in variable bit-rate
      applications, since the algorithm turns to the standard JPEG method whenever it
      is necessary at higher bit rates.

PMID- 16948300
TI  - Semi-regular representation and progressive compression of 3-D dynamic mesh
      sequences.
AB  - We propose an algorithm that represents three-dimensional dynamic objects with a
      semi-regular mesh sequence and compresses the sequence using the spatiotemporal
      wavelet transform. Given an irregular mesh sequence, we construct a semi-regular
      mesh structure for the first frame and then map it to subsequent frames based on
      the hierarchical motion estimation. The regular structure of the resulting mesh
      sequence facilitates the application of advanced coding schemes and other signal
      processing techniques. To encode the mesh sequence compactly, we develop an
      embedded coding scheme, which supports signal-to-noise ratio and temporal
      scalability modes. Simulation results demonstrate that the proposed algorithm
      provides significantly better compression performance than the static mesh coder,
      which encodes each frame independently.

PMID- 16948299
TI  - Lossless compression of VLSI layout image data.
AB  - We present a novel lossless compression algorithm called Context Copy
      Combinatorial Code (C4), which integrates the advantages of two very disparate
      compression techniques: context-based modeling and Lempel-Ziv (LZ) style copying.
      While the algorithm can be applied to many lossless compression applications,
      such as document image compression, our primary target application has been
      lossless compression of integrated circuit layout image data. These images
      contain a heterogeneous mix of data: dense repetitive data better suited to LZ
      style coding, and less dense structured data, better suited to context-based
      encoding. As part of C4, we have developed a novel binary entropy coding
      technique called combinatorial coding which is simultaneously as efficient as
      arithmetic coding, and as fast as Huffman coding. Compression results show C4
      outperforms JBIG, ZIP, BZIP2, and two-dimensional LZ, and achieves lossless
      compression ratios greater than 22 for binary layout image data, and greater than
      14 for gray-pixel image data.

PMID- 16948301
TI  - 3-band motion-compensated temporal structures for scalable video coding.
AB  - Recent breakthroughs in motion-compensated temporal wavelet filtering have
      finally enabled implementation of highly efficient scalable and error-resilient
      video codecs. These new wavelet codecs provide numerous advantages over
      nonscalable conventional solutions techniques based on motion-compensated
      prediction, such as no recursive predictive loop, separation of noise and
      sampling artifacts from the content through use of longer temporal filters,
      removal of long range as well as short range temporal redundancies, etc.
      Moreover, these wavelet video coding schemes can provide flexible spatial,
      temporal, signal-to-noise ratio and complexity scalability with fine granularity
      over a large range of bit rates, while maintaining a very high coding efficiency.
      However, most motion-compensated wavelet video schemes are based on classical two
      band decompositions that offer only dyadic factors of temporal scalability. In
      this paper, we propose a three-band temporal structure that extends the concept
      of motion-compensated temporal filtering (MCTF) that was introduced in the
      classical lifting framework. These newly introduced structures provide higher
      temporal scalability flexibility, as well as improved compression performance
      compared with dyadic Haar MCTF.

PMID- 16948302
TI  - A global approach for solving evolutive heat transfer for image denoising and
      inpainting.
AB  - This paper proposes an alternative to partial differential equations (PDEs) for
      solving problems in computer vision based on evolutive heat transfer.
      Traditionally, the method for solving such physics-based problems is to
      discretize and solve a PDE by a purely mathematical process. Instead of using the
      PDE, we propose to use the global heat principle and to decompose it into basic
      laws. We show that some of these laws admit an exact global version since they
      arise from conservative principles. We also show that the assumptions made about
      the other basic Iaws can be made wisely, taking into account knowledge about the
      problem and the domain. The numerical scheme is derived in a straightforward way
      from the modeled problem, thus providing a physical explanation for each step in
      the solution. The advantage of such an approach is that it minimizes the
      approximations made during the whole process and it modularizes it, allowing
      changing the application to a great number of problems. We apply the scheme to
      two applications: image denoising and inpainting which are modeled with heat
      transfer. For denoising, we propose a new approximation for the conductivity
      coefficient and we add thin lines to the features in order to block diffusion.

PMID- 16948303
TI  - Edge-preserving image denoising via optimal color space projection.
AB  - Denoising of color images can be done on each color component independently.
      Recent work has shown that exploiting strong correlation between high-frequency
      content of different color components can improve the denoising performance. We
      show that for typical color images high correlation also means similarity, and
      propose to exploit this strong intercolor dependency using an optimal
      luminance/color-difference space projection. Experimental results confirm that
      performing denoising on the projected color components yields superior denoising
      performance, both in peak signal-to-noise ratio and visual quality sense,
      compared to that of existing solutions. We also develop a novel approach to
      estimate directly from the noisy image data the image and noise statistics, which
      are required to determine the optimal projection.

PMID- 16948304
TI  - Standardization of edge magnitude in color images.
AB  - Edge detection is a useful task in low-level image processing. The efficiency of
      many image processing and computer vision tasks depends on the perfection of
      detecting meaningful edges. To get a meaningful edge, thresholding is almost
      inevitable in any edge detection algorithm. Many algorithms reported in the
      literature adopt ad hoc schemes for this purpose. These algorithms require the
      threshold values to be supplied and tuned by the user. There are many high-level
      tasks in computer vision which are to be performed without human intervention.
      Thus, there is a need to develop a scheme where a single set of threshold values
      would give acceptable results for many color images. In this paper, an attempt
      has been made to devise such an algorithm. Statistical variability of partial
      derivatives at each pixel is used to obtain standardized edge magnitude and is
      thresholded using two threshold values. The advantage of standardization is
      evident from the results obtained.

PMID- 16948305
TI  - Performance analysis of motion-compensated de-interlacing systems.
AB  - A lot of research has been conducted on motion-compensated (MC) de-interlacing,
      but there are very few publications that discuss the performances of de
      interlacing quantatively. The various methods are compared through their
      performance on known video sequences. Linear system analysis of interlaced video
      and de-interlacer are proposed in. It is well established that the performance of
      the MC methods outperform the fixed or motion-adaptive methods when the motion
      vectors used are reliable and true to the scene content. Being an open-loop
      process the performance of the MC de-interlacers degrade drastically when there
      are motion vector errors. In this paper, a linear system analysis of MC video
      upconversion systems is presented and the effects of motion vector accuracy on
      system performance are analyzed. We investigate the various factors that
      contribute to the motion vector inaccuracy, such as incorrect motion modelling,
      acceleration between the frames, and insufficient interpolation kernel.

PMID- 16948306
TI  - Improved lossless intra coding for H.264/MPEG-4 AVC.
AB  - A new lossless intra coding method based on sample-by-sample differential pulse
      code modulation (DPCM) is presented as an enhancement of the H.264/MPEG-4 AVC
      standard. The H.264/AVC design includes a multidirectional spatial prediction
      method to reduce spatial redundancy by using neighboring samples as a prediction
      for the samples in a block of data to be encoded. In the new lossless intra
      coding method, the spatial prediction is performed based on samplewise DPCM
      instead of in the block-based manner used in the current H.264/AVC standard,
      while the block structure is retained for the residual difference entropy coding
      process. We show that the new method, based on samplewise DPCM, does not have a
      major complexity penalty, despite its apparent pipeline dependencies. Experiments
      show that the new lossless intra coding method reduces the bit rate by
      approximately 12% in comparison with the lossless intra coding method previously
      included in the H.264/AVC standard. As a result, the new method is currently
      being adopted into the H.264/AVC standard in a new enhancement project.

PMID- 16948307
TI  - Polyharmonic smoothing splines and the multidimensional Wiener filtering of
      fractal-like signals.
AB  - Motivated by the fractal-like behavior of natural images, we develop a smoothing
      technique that uses a regularization functional which is a fractional iterate of
      the Laplacian. This type of functional was initially introduced by Duchon for the
      approximation of nonuniformily sampled, multidimensional data. He proved that the
      general solution is a smoothing spline that is represented by a linear
      combination of radial basis functions (RBFs). Unfortunately, this is tedious to
      implement for images because of the poor conditioning of RBFs and their lack of
      decay. Here, we present a much more efficient method for the special case of a
      uniform grid. The key idea is to express Duchon's solution in a fractional
      polyharmonic B-spline basis that spans the same space as the RBFs. This allows us
      to derive an algorithm where the smoothing is performed by filtering in the
      Fourier domain. Next, we prove that the above smoothing spline can be optimally
      tuned to provide the MMSE estimation of a fractional Brownian field corrupted by
      white noise. This is a strong result that not only yields the best linear filter
      (Wiener solution), but also the optimal interpolation space, which is not
      bandlimited. It also suggests a way of using the noisy data to identify the
      optimal parameters (order of the spline and smoothing strength), which yields a
      fully automatic smoothing procedure. We evaluate the performance of our algorithm
      by comparing it against an oracle Wiener filter, which requires the knowledge of
      the true noiseless power spectrum of the signal. We find that our approach
      performs almost as well as the oracle solution over a wide range of conditions.

PMID- 16948308
TI  - A subspace matching color filter design methodology for a multispectral imaging
      system.
AB  - In this paper, we present a methodology to design filters for an imaging system
      to improve the accuracy of the spectral measurements for families of reflective
      surfaces. We derive the necessary and sufficient conditions that the sensor space
      of the system must obey in order to measure the spectral reflectance of the
      surfaces accurately. Through simulations, we show how these conditions can be
      applied to design filters using a set of sample spectral data acquired from
      extracted teeth. For this set of data, we also compare our results to those of
      Wolski's method, a conventional filter design method which produces filters that
      recover tristimulus values of surfaces accurately under several illuminants. We
      show that our method produces filters that capture the spectral reflectance
      better given the same number of measurements. The errors in predicting the color
      of the sample data are much lower under every test illuminant when the filters
      designed with our method are used.

PMID- 16948309
TI  - Using hidden scale for salient object detection.
AB  - This paper describes a method for detecting salient regions in remote-sensed
      images, based on scale and contrast interaction. We consider the focus on salient
      structures as the first stage of an object detection/recognition algorithm, where
      the salient regions are those likely to contain objects of interest. Salient
      objects are modeled as spatially localized and contrasted structures with any
      kind of shape or size. Their detection exploits a probabilistic mixture model
      that takes two series of multiscale features as input, one that is more sensitive
      to contrast information, and one that is able to select scale. The model combines
      them to classify each pixel in salient/nonsalient class, giving a binary
      segmentation of the image. The few parameters are learned with an EM-type
      algorithm.

PMID- 16948310
TI  - A hybrid SEM algorithm for high-dimensional unsupervised learning using a finite
      generalized Dirichlet mixture.
AB  - This paper applies a robust statistical scheme to the problem of unsupervised
      learning of high-dimensional data. We develop, analyze, and apply a new finite
      mixture model based on a generalization of the Dirichlet distribution. The
      generalized Dirichlet distribution has a more general covariance structure than
      the Dirichlet distribution and offers high flexibility and ease of use for the
      approximation of both symmetric and asymmetric distributions. We show that the
      mathematical properties of this distribution allow high-dimensional modeling
      without requiring dimensionality reduction and, thus, without a loss of
      information. This makes the generalized Dirichlet distribution more practical and
      useful. We propose a hybrid stochastic expectation maximization algorithm (HSEM)
      to estimate the parameters of the generalized Dirichlet mixture. The algorithm is
      called stochastic because it contains a step in which the data elements are
      assigned randomly to components in order to avoid convergence to a saddle point.
      The adjective "hybrid" is justified by the introduction of a Newton-Raphson step.
      Moreover, the HSEM algorithm autonomously selects the number of components by the
      introduction of an agglomerative term. The performance of our method is tested by
      the classification of several pattern-recognition data sets. The generalized
      Dirichlet mixture is also applied to the problems of image restoration, image
      object recognition and texture image database summarization for efficient
      retrieval. For the texture image summarization problem, results are reported for
      the Vistex texture image database from the MIT Media Lab.

PMID- 16948311
TI  - Fractal-wavelet image denoising revisited.
AB  - The essence of fractal image denoising is to predict the fractal code of a
      noiseless image from its noisy observation. From the predicted fractal code, one
      can generate an estimate of the original image. We show how well fractal-wavelet
      denoising predicts parent wavelet subtress of the noiseless image. The
      performance of various fractal-wavelet denoising schemes (e.g., fixed
      partitioning, quadtree partitioning) is compared to that of some standard wavelet
      thresholding methods. We also examine the use of cycle spinning in fractal-based
      image denoising for the purpose enhancing the denoised estimates. Our
      experimental results show that these fractal-based image denoising methods are
      quite competitive with standard wavelet thresholding methods for image denoising.
      Finally, we compare the performance of the pixel- and wavelet-based fractal
      denoising schemes.

PMID- 16948312
TI  - CCD noise removal in digital images.
AB  - In this work, we propose a denoising scheme to restore images degraded by CCD
      noise. The CCD noise model, measured in the space of incident light values (light
      space), is a combination of signal-independent and signal-dependent noise terms.
      This model becomes more complex in image brightness space (normal camera output)
      due to the nonlinearity of the camera response function that transforms incoming
      data from light space to image space. We develop two adaptive restoration
      techniques, both accounting for this nonlinearity. One operates in light space,
      where the relationship between the incident light and light space values is
      linear, while the second method uses the transformed noise model to operate in
      image space. Both techniques apply multiple adaptive filters and merge their
      outputs to give the final restored image. Experimental results suggest that light
      space denoising is more efficient, since it enables the design of a simpler
      filter implementation. Results are given for real images with synthetic noise
      added, and for images with real noise.

PMID- 16948313
TI  - SAR image filtering based on the heavy-tailed Rayleigh model.
AB  - Synthetic aperture radar (SAR) images are inherently affected by a signal
      dependent noise known as speckle, which is due to the radar wave coherence. In
      this paper, we propose a novel adaptive despeckling filter and derive a maximum a
      posteriori (MAP) estimator for the radar cross section (RCS). We first employ a
      logarithmic transformation to change the multiplicative speckle into additive
      noise. We model the RCS using the recently introduced heavy-tailed Rayleigh
      density function, which was derived based on the assumption that the real and
      imaginary parts of the received complex signal are best described using the alpha
      stable family of distribution. We estimate model parameters from noisy
      observations by means of second-kind statistics theory, which relies on the
      Mellin transform. Finally, we compare the proposed algorithm with several
      classical speckle filters applied on actual SAR images. Experimental results show
      that the homomorphic MAP filter based on the heavy-tailed Rayleigh prior for the
      RCS is among the best for speckle removal.

PMID- 16948314
TI  - On the estimation of the coefficient of variation for anisotropic diffusion
      speckle filtering.
AB  - In this paper, we focus on the problem of speckle removal by means of anisotropic
      diffusion and, specifically, on the importance of the correct estimation of the
      statistics involved. First, we derive an anisotropic diffusion filter that does
      not depend on a linear approximation of the speckle model assumed, which is the
      case of a previously reported filter, namely, SRAD. Then, we focus on the problem
      of estimation of the coefficient of variation of both signal and noise and of
      noise itself. Our experiments indicate that neighborhoods used for parameter
      estimation do not need to coincide with those used in the diffusion equations.
      Then, we show that, as long as the estimates are good enough, the filter proposed
      here and the SRAD perform fairly closely, a fact that emphasizes the importance
      of the correct estimation of the coefficients of variation.

PMID- 16948315
TI  - Rotation-invariant texture retrieval with Gaussianized steerable pyramids.
AB  - This paper presents a novel rotation-invariant image retrieval scheme based on a
      transformation of the texture information via a steerable pyramid. First, we fit
      the distribution of the subband coefficients using a joint alpha-stable sub
      Gaussian model to capture their non-Gaussian behavior. Then, we apply a
      normalization process in order to Gaussianize the coefficients. As a result, the
      feature extraction step consists of estimating the covariances between the
      normalized pyramid coefficients. The similarity between two distinct texture
      images is measured by minimizing a rotation-invariant version of the Kullback
      Leibler Divergence between their corresponding multivariate Gaussian
      distributions, where the minimization is performed over a set of rotation angles.

PMID- 16948316
TI  - A cost-effective line-based light-balancing technique using adaptive processing.
AB  - The camera imaging system has been widely used; however, the displaying image
      appears to have an unequal light distribution. This paper presents novel light
      balancing techniques to compensate uneven illumination based on adaptive signal
      processing. For text image processing, first, we estimate the background level
      and then process each pixel with nonuniform gain. This algorithm can balance the
      light distribution while keeping a high contrast in the image. For graph image
      processing, the adaptive section control using piecewise nonlinear gain is
      proposed to equalize the histogram. Simulations show that the performance of
      light balance is better than the other methods. Moreover, we employ line-based
      processing to efficiently reduce the memory requirement and the computational
      cost to make it applicable in real-time systems.

PMID- 16948317
TI  - Image denoising using total least squares.
AB  - In this paper, we present a method for removing noise from digital images
      corrupted with additive, multiplicative, and mixed noise. An image patch from an
      ideal image is modeled as a linear combination of image patches from the noisy
      image. We propose to fit this model to the real-world image data in the total
      least square (TLS) sense, because the TLS formulation allows us to take into
      account the uncertainties in the measured data. We develop a method to reduce the
      contribution from the irrelevant image patches, which will sharpen the edges and
      reduce edge artifacts at the same time. Although the proposed algorithm is
      computationally demanding, the image quality of the output image demonstrates the
      effectiveness of the TLS algorithms.

PMID- 16948318
TI  - Deformable shape finding with models based on kernel methods.
AB  - In this paper, a new kernel-based deformable model is proposed for detecting
      deformable shapes. To incorporate valuable information for shape detection, such
      as edge orientations into the shape representation, a novel scheme based on
      kernel methods has been utilized. The variation model of a deformable shape is
      established by a set of training samples of the shape represented in a kernel
      feature space. The proposed deformable model consists of two parts: a set of
      basis vectors describing the sample subspace, including the shape representations
      of the training samples, and a feasibility constraint generated by the one-class
      support vector machine to describe the feasible region of the training samples in
      the sample subspace. The aim of the proposed feasibility constraint is to avoid
      finding some invalid shapes. By using the proposed deformable model, an efficient
      algorithm without initial solutions is developed for shape detection. The
      proposed approach was tested against real images. Experimental results show the
      effectiveness of the proposed deformable model and prove the feasibility of the
      proposed approach.

PMID- 16948319
TI  - Unsupervised multiscale color image segmentation based on MDL principle.
AB  - We present an unsupervised multiscale color image segmentation algorithm. The
      basic idea is to apply mean shift clustering to obtain an over-segmentation and
      then merge regions at multiple scales to minimize the minimum description length
      criterion. The performance on the Berkeley segmentation benchmark campares
      favorably with some existing approaches.

PMID- 16948320
TI  - Nonparametric statistical snake based on the minimum stochastic complexity.
AB  - We propose a nonparametric statistical snake technique that is based on the
      minimization of the stochastic complexity (minimum description length principle).
      The probability distributions of the gray levels in the different regions of the
      image are described with step functions with parameters that are estimated. The
      segmentation is thus obtained by minimizing a criterion that does not include any
      parameter to be tuned by the user. We illustrate the robustness of this technique
      on various types of images with level set and polygonal contour models. The
      efficiency of this approach is also analyzed in comparison with parametric
      statistical techniques.

PMID- 16948321
TI  - Moving window-based double Haar wavelet transform for image processing.
AB  - Image denoising is a lively research field. The classical nonlinear filters used
      for image denoising, such as median filter, are based on a local analysis of the
      pixels within a moving window. Recently, the research of image denoising has been
      focused on the wavelet domain. Compared to the classical nonlinear filters, it is
      based on a global multiscale analysis of images. Apparently, the wavelet
      transform can be embedded in a moving window. Thus, a moving window-based local
      multiscale analysis is obtained. In this paper, based on the Haar wavelet, a
      class of nonorthogonal multi-channel filter bank with its corresponding wavelet
      shrinkage called Lee shrinkage is derived. As a special case of this filter bank,
      the double Haar wavelet transform is introduced. Examples show that it is
      suitable for a moving window-based local multiscale analysis used for image
      denoising, edge detection, and edge enhancement.

PMID- 16948322
TI  - The design and evaluation of a generic method for generating mosaicked
      multispectral filter arrays.
AB  - The technology of color filter arrays (CFA) has been widely used in the digital
      camera industry since it provides several advantages like low cost, exact
      registration, and strong robustness. The same motivations also drive the design
      of multispectral filter arrays (MSFA), in which more than three spectral bands
      are used. Although considerable research has been reported to optimally
      reconstruct the full-color image using various demosaicking algorithms, studies
      on the intrinsic properties of these filter arrays as well as the underlying
      design principles have been very limited. Given a set of representative spectral
      bands, the design of an MSFA involves two issues: the selection of tessellation
      mechanisms and the arrangement/layout of different spectral bands. We develop a
      generic MSFA generation method starting from a checkerboard pattern. We show,
      through case studies, that most of the CFAs currently used by the industry can be
      derived as special cases of MSFAs generated using the generic algorithm. The
      performance of different MSFAs are evaluated based on their intrinsic properties,
      namely, the spatial uniformity and the spectral consistency. We design two
      metrics, static coefficient and consistency coefficient, to measure these two
      parameters, respectively. The experimental results demonstrate that the generic
      algorithm can generate optimal or near-optimal MSFAs in both the rectangular and
      the hexagonal domains.

PMID- 16948323
TI  - A generalization of the two-dimensional prolate spheroidal wave function method
      for nonrectilinear MRI data acquisition methods.
AB  - The two-dimensional (2-D) prolate spheroidal wave function (2-D PSWF) method was
      previously introduced as an efficient method for trading off between spatial and
      temporal resolution in magnetic resonance imaging (MRI), with minimal penalty due
      to truncation and partial volume effects. In the 2-D PSWF method, the k-space
      sampling area and a matching 2-D PSWF filter, with optimal signal concentration
      and minimal truncation artifacts, are determined by the shape and size of a given
      convex region of interest (ROI). The spatial information in the reduced k-space
      data is used to calculate the total image intensity over a nonsquare ROI instead
      of producing a low-resolution image. This method can be used for tracking dynamic
      signals from non-square ROIs using a reduced k-space sampling area, while
      achieving minimal signal leakage. However, the previous theory is limited to the
      case of rectilinear sampling. In order to make the 2-D PSWF method more suitable
      for dynamic studies, this paper presents a generalized version of the 2-D PSWF
      theory that can be applied to nonrectilinear data acquisition methods. The method
      is applied to an fMRI study using a spiral trajectory, which illustrates the
      methods efficiency at tracking hemodynamic signals with high temporal resolution.

PMID- 16948324
TI  - Multigrid tomographic inversion with variable resolution data and image spaces.
AB  - A multigrid inversion approach that uses variable resolutions of both the data
      space and the image space is proposed. Since the computational complexity of
      inverse problems typically increases with a larger number of unknown image pixels
      and a larger number of measurements, the proposed algorithm further reduces the
      computation relative to conventional multigrid approaches, which change only the
      image space resolution at coarse scales. The advantage is particularly important
      for data-rich applications, where data resolutions may differ for different
      scales. Applications of the approach to Bayesian reconstruction algorithms in
      transmission and emission tomography with a generalized Gaussian Markov random
      field image prior are presented, both with a Poisson noise model and with a
      quadratic data term. Simulation results indicate that the proposed multigrid
      approach results in significant improvement in convergence speed compared to the
      fixed-grid iterative coordinate descent method and a multigrid method with fixed
      data resolution.

PMID- 16948325
TI  - High dynamic range image rendering with a Retinex-based adaptive filter.
AB  - We propose a new method to render high dynamic range images that models global
      and local adaptation of the human visual system. Our method is based on the
      center-surround Retinex model. The novelties of our method is first to use an
      adaptive filter, whose shape follows the image high-contrast edges, thus reducing
      halo artifacts common to other methods. Second, only the luminance channel is
      processed, which is defined by the first component of a principal component
      analysis. Principal component analysis provides orthogonality between channels
      and thus reduces the chromatic changes caused by the modification of luminance.
      We show that our method efficiently renders high dynamic range images and we
      compare our results with the current state of the art.

PMID- 16948326
TI  - Still-image watermarking robust to local geometric distortions.
AB  - Geometrical distortions are the Achilles heel for many watermarking schemes. Most
      countermeasures proposed in the literature only address the problem of global
      affine transforms (e.g., rotation, scaling, and translation). In this paper, we
      propose an original blind watermarking algorithm robust to local geometrical
      distortions such as the deformations induced by Stirmark. Our method consists in
      adding a predefined additional information to the useful message bits at the
      insertion step. These additional bits are labeled as resynchronization bits or
      reference bits and they are modulated in the same way as the information bits.
      During the extraction step, the reference bits are used as anchor points to
      estimate and compensate for small local and global geometrical distortions. The
      deformations are approximated using a modified basic optical flow algorithm.

PMID- 16948327
TI  - Level set-based bimodal segmentation with stationary global minimum.
AB  - In this paper, we propose a new level set-based partial differential equation
      (PDE) for the purpose of bimodal segmentation. The PDE is derived from an energy
      functional which is a modified version of the fitting term of the Chan-Vese
      model. The energy functional is designed to obtain a stationary global minimum,
      i.e., the level set function which evolves by the Euler-Lagrange equation of the
      energy functional has a unique convergence state. The existence of a global
      minimum makes the algorithm invariant to the initialization of the level set
      function, whereas the existence of a convergence state makes it possible to set a
      termination criterion on the algorithm. Furthermore, since the level set function
      converges to one of the two fixed values which are determined by the amount of
      the shifting of the Heaviside functions, an initialization of the level set
      function close to those values can result in a fast convergence.

PMID- 16948328
TI  - HFMA talks revenue in Orlando. Some of the industry's top chief financial
      officers recently chatted about how best to bring in dollars and cents.

PMID- 16948329
TI  - Insurers entertain new models at AHIP. Payers talk of becoming more consumer
      centric at their recently held annual conference.

PMID- 16948330
TI  - AHIC sets the table. The American Health Information Community has an ambitious
      roadmap for 2006 and beyond.

PMID- 16948331
TI  - Seeking the source. As deployments begin to gather steam, the industry is taking
      a closer look at open-source solutions.

PMID- 16948332
TI  - Real solutions for RHIO problems. Pioneering data exchange groups seek
      sustainability by solving business problems for members.

PMID- 16948333
TI  - Safety when it counts. Patient safety moves forward in some hospitals but, seven
      years after the "Quality chasm" report, progress is still spotty.

PMID- 16948334
TI  - Enhancing the intranet. Christina Birrer moves North Shore forward with an
      updated intranet.

PMID- 16948335
TI  - Infection protection. Surveillance technologies can help healthcare organizations
      better detect and respond to infections.

PMID- 16948336
TI  - NPI on the way. Healthcare providers would be wise to begin the process of
      acquiring national provider identifiers.

PMID- 16948337
TI  - Is practicing medicine virtually impossible? Employing virtual medicine
      technologies and techniques can help propel healthcare into the future.

PMID- 16948338
TI  - El Camino turns the page. A pioneering hospital recently exchanged the world's
      first medical information system for a next-generation solution.

PMID- 16948339
TI  - Getting connected. XML and .NET framework can provide the bridge to link payers,
      providers and consumers.

PMID- 16948340
TI  - RHIO & vendor growing together. The Utah Health Information Network continues to
      work in tandem with Columbus, Ohio-based HTP.

PMID- 16948341
TI  - Prepping for disaster. Intermountain Health Care invests in technology to help
      with business-continuity planning.

PMID- 16948342
TI  - Ruling out food allergy in pediatrics and preventing the "march" of the allergic
      child.
AB  - When a child presents with an allergic symptom, the general pediatrician needs to
      discriminate which patient has to be sent to the specialist for an allergologic
      evaluation. If referred, the child will undergo not only skin-prick test, but
      also more complex specialistic evaluations that we define here as "the march of
      allergic children." The objective of this article is to overview the clinical
      evidence about possible diagnostic interventions to avoid unuseful referrals of
      children reported with allergy from the general to the specialist level. Data
      sources include PubMed, using a search algorithm selecting for diagnostic studies
      of respiratory and food allergy in all children to August 2005. Also included are
      commentaries based on the authors' clinical experience in the allergy unit of a
      University Hospital in Italy. No study prospectively assessed the rule-out
      efficacy of clinical history, physical evaluation, and skin-prick test panels on
      the allergic disease. Three prospective studies on in vitro panels of specific
      IgE sensitization matched entry criteria. Diverse trial designs and diagnostic
      criteria precluded meta-analytic methods. The use of in vitro panels proved
      effective in ruling out the allergic condition in children. The screening
      efficacy of panels of food and respiratory skin-prick tests remains to be
      evaluated. With sensitivities and negative predictive values exceeding 90%, in
      vitro panels can inform the decisions of pediatricians in their capacity as
      gateway to specialist care. Avoiding the march of allergic children from the GPs
      to the secondary level is a more realistic goal than preventing the allergic
      march.

PMID- 16948343
TI  - Update on the use of montelukast in pediatric asthma.
AB  - Cysteinyl leukotrienes are inflammatory bioactive lipids produced by various
      cells. They are present in increased amounts in airway secretions of all
      different asthma phenotypes and can induce all the inflammatory changes observed
      in the airways of asthmatic patients. For this reason, an attempt to inhibit the
      actions of these mediators through the use of cysteinyl receptor antagonists
      appears rational. Montelukast belongs to this new class of drugs, which has been
      proved effective in asthmatic children and its safety profile is comparable with
      that of placebo. The major advantages of this drug are its once-daily oral
      administration, which increases adherence to the therapeutic regimen; its long
      term persistent efficacy in the prevention of exercise-induced
      bronchoconstriction; its possible preventive activity on viral-induced asthma
      exacerbations; and its complementary and additive effects when used with inhaled
      corticosteroids. As established for all drugs commonly used in the treatment of
      asthma, there is an interindividual variability also in response to montelukast.
      Therefore, it is important that caregivers evaluate treatment effect objectively
      in every asthmatic child to provide the single patient with a therapeutic regimen
      allowing the best quality of life.

PMID- 16948344
TI  - The determination of asthma, rhinitis, eczema, and atopy prevalence in 9- to 11
      year-old children in the city of Izmir.
AB  - The International Study of Asthma and Allergies in Childhood (ISAAC) phase II was
      designed to allow comparisons between populations in different countries and to
      investigate possible etiologic factors. This study was conducted to better
      delineate the prevalence and etiologic factors of asthma, rhinitis, and eczema in
      Izmir (Turkey) and to be included in the international comparisons by using a
      standard methodology of ISAAC phase II. The questionnaire was distributed to 2112
      students in the 3rd, 4th, and 5th grades of 12 selected primary schools in urban
      and rural boroughs of Izmir. One thousand two hundred seventeen of these
      questionnaires were evaluated and physical examinations and skin-prick tests were
      performed on 1098 of these children. The prevalence values were 15.9% for recent
      wheezing and 4.8% for physician-diagnosed asthma. The prevalence of sneezing or
      runny or blocked nose in the past 12 months when the child did not have a cold or
      flu was 30%. The prevalence of physician-diagnosed allergic rhinitis was 17%. The
      prevalence of an itchy rash that was coming and going for at least 6 months was
      7.2% and the prevalence of physician-diagnosed eczema was 4.9%. Atopic
      sensitization prevalence in the population was 8.8% with house-dust mite
      sensitization being the most frequent one. Secretion rales and sibilant wheezing
      rhoncus were detected in 2.7% of children by chest auscultation. In 1.1% of
      children flexural dermatitis was detected. Objective tests are necessary for
      epidemiologic studies of the aforementioned diseases.

PMID- 16948345
TI  - Identification of asthma risk factors in Mexico City in an International Study of
      Asthma and Allergy in Childhood survey.
AB  - The International Study of Asthma and Allergy in Childhood (ISAAC) has assessed
      the prevalence of asthma, as well as the factors related to the disease in
      different countries. The aim of this study was to identify asthma risks factors
      in Mexico City. Data were obtained from questionnaires of children participating
      in a phase 3b ISAAC survey. Two thousand ninety-eight boys and 2008 girls were
      recruited in the 6- to 7-year-old group and 3243 boy and 3333 girls were
      recruited in the 13- to 14-year-old group. Logistic regression was used to
      determine the asthma risks factors. In the logistic regression for cumulative and
      current asthma prevalence, the variables allergic rhinitis and atopic dermatitis
      were the most important risk factors with the highest odds ratios (OR > 1.5; p <
      0.05). The use of antibiotics and paracetamol in the first 12 months of life were
      related to cumulative asthma in both genders in the 6- to 7-year-old group.
      Contact of pregnant mother with farm animals was positively related with
      cumulative asthma in boys in the 6- to 7-year-old group. The main factors
      associated with the cumulative and current prevalence of asthma in both age
      groups were atopic dermatitis and allergic rhinitis. Future interventions for the
      prevention and early diagnosis and treatment could be focused in the natural
      history of the atopic march.

PMID- 16948346
TI  - Asthma prevalence in children living in north Mexico City and a comparison with
      other Latin American cities and world regions.
AB  - Reports of previous studies done without following the international guidelines
      in different cities of Mexico showed a decrease in asthma prevalence. The aim of
      this study was to determine the prevalence and severity of asthma symptoms in
      children and teenagers living in north Mexico City and compare them with those of
      other Latin American cities and world regions. The cross-sectional survey
      followed the protocol of the International Study of Asthma and Allergies in
      Childhood IIIb phase survey. The study population included children 6-7 years old
      and teenagers 13-14 years old from randomly selected primary and secondary
      schools. There were 1629 boys and 1582 girls in the group of 6- to 7-year-old
      children and 2039 boys and 1860 girls in the 13- to 14-year-old group. "Wheezing
      or whistling in the chest at any time in the past" was present in 19.2% (95%
      confidence interval [CI], 17.9, 20.6) of the children and in 17.0% (95% CI, 15.8,
      18.1) of the teenagers; "wheezing or whistling in the chest in the last 12
      months" was reported in 6.8% (95% CI, 5.9, 7.6) of the children and 9.9% (95% CI,
      9.0, 10.8) of the teenagers; "asthma ever" was claimed in 4.5% (95% CI, 3.8, 5.2)
      of the children and 8.0% (95% CI, 7.1, 8.8) of the teenagers. These prevalences
      were low compared with other ISAAC Latin American surveys and intermediate in
      comparison with worldwide regional prevalences reported by ISAAC surveys. The
      prevalence of asthma is low in Mexico City in comparison with other surveyed
      locations, but the number of patients with asthma makes it an important issue for
      Mexican public health programs.

PMID- 16948347
TI  - Early predictors for adult asthma and lung function abnormalities in infants
      hospitalized for bronchiolitis: a prospective 18- to 20-year follow-up.
AB  - In the present cohort, 85% of infants hospitalized for wheezing outgrew their
      symptoms until puberty, but 30-40% had asthma, depending on criteria, again in
      young adulthood. The aim of this study was to determine early predictors for
      adulthood asthma, bronchial reactivity, and lung function abnormalities in
      infants hospitalized for bronchiolitis. Fifty-two children hospitalized for
      bronchiolitis at < 2 years of age were restudied at the median age of 19 years.
      Wheezing histories and early risk factors for later asthma were recorded
      prospectively during infancy. The follow-up study consisted of a written
      questionnaire, physical examination, flow-volume spirometry, methacholine
      inhalation challenge, home peak expiratory flow monitoring, and skin-prick tests.
      In univariate analyses, parental asthma and repeated wheezing at age the age of 0
      1 years and 0-2 years predicted adulthood asthma. Repeated wheezing at age the
      age of 0-1 years predicted later bronchial reactivity. Onset and recurrence of
      wheezing at < 1 year of age, parental atopy and asthma, and maternal smoking
      during infancy were related to subnormal lung function parameters. In
      multivariate logistic regression, adjusted for sex, age on admission, current
      smoking, and atopy in infancy and, currently, repeated wheezing both at < 1 year
      and < 2 years of age was an independent predictor for adulthood asthma. Parental
      asthma and repeated wheezing predict adulthood asthma in infants hospitalized for
      bronchiolitis, and maternal smoking predisposes them to lung function impairment
      in adulthood.

PMID- 16948348
TI  - Passive smoking in asthmatic children: effect of a "smoke-free house" measured by
      urinary cotinine levels.
AB  - Environmental tobacco smoke (ETS) decreases pulmonary function and increases both
      airway reactivity and frequency of child asthma exacerbations. True exposure is
      related not only to parents smoking and to the number of cigarettes that they
      smoke, but also to involuntary smoking in public places. The aim of this study
      was to evaluate, by measuring urinary cotinine levels, the exposure to ETS in
      asthmatic children and the contribution of unapparent smoke exposure. Twenty
      asthmatic children (aged 7-12 years) were evaluated on the 1st day (TO) and after
      a week (T1) in a "smoke-free house." The mean level of urinary cotinine in
      children was 15.8 +/- 2.7 ng/mg of creatinine at TO and 4.2 +/- 0.6 ng/mg of
      creatinine at T1 (p < 0.0001). The urinary cotinine concentrations were higher in
      children living with smoking parents (21.8 +/- 3.4 ng/mg creatinine) compared
      with children not exposed to parental smoke (6.8 +/- 3.0 ng/mg creatinine; p =
      0.017). The number of cigarettes smoked by parents correlates with the urinary
      cotinine levels (p = 0.005; r = 0.64). Urinary cotinine levels significantly
      decreased after the avoidance of ETS in children exposed to parental smoke (21.8
      +/- 3.4 ng/mg at TO; 5.0 +/- 0.8 ng/mg at T1; p < 0.001) and also in children
      whose parents declared to be nonsmokers (6.8 +/- 1.2 ng/mg at TO; 3.0 +/- 0.8
      ng/mg at T1; p = 0.006). Our data confirm the widespread indirect and undetected
      tobacco smoke exposure in children with chronic asthma and the relevance of an
      evaluation with an objective method of the exposure to second-hand smoke.

PMID- 16948349
TI  - Bronchiectasis and chronic asthma: how common in pediatrics?
AB  - Asthma represents one of the most common chronic medical conditions affecting
      children. Although complications of asthma are rare, they deserve consideration
      when treating children with asthma. The aim of this study was report our
      experience with an 11-year-old boy with asthma that was complicated by
      bronchiectasis and to review our hospital's 10-year experience with
      bronchiectasis. We observed clinical and laboratory findings in a young boy with
      chronic asthma who developed bronchiectasis, reviewed medical records of 53
      children with bronchiectasis followed at a university children's hospital to
      identify etiologies of bronchiectasis, and reviewed articles in the medical
      literature. Complications of asthma along with their diagnosis, pathogenesis, and
      treatment options are outlined in the discussion section. We describe the case of
      an 11-year-old boy with chronic asthma who did not respond to conventional asthma
      management and was found to have bronchiectasis. A detailed workup undertaken to
      identify the cause was negative for usual etiologies of bronchiectasis. In this
      patient, bronchiectasis was felt to be secondary to a long-standing history of
      asthma. Aggressive treatment of bronchiectasis led to significant improvement of
      asthma. Among 53 patients admitted for bronchiectasis, only 3 cases (5.6%) of
      asthma were identified. Cystic fibrosis (50.9%) and infection (13.2%) were the
      most common etiologies identified in our hospital's experience. No clear etiology
      was identified in 1.8% of patients. Although rare, bronchiectasis does occur in
      patients with chronic asthma. It is important that complications be recognized
      and treated for optimal management of asthma.

PMID- 16948350
TI  - Functional assessment of allergic asthmatic children while asymptomatic.
AB  - The aim of this study was to detect the best test lung function to identify
      abnormalities in asthmatic children while asymptomatic. We studied 200 asthmatic
      children. Patients were evaluated by questionnaire to evaluate the presence of
      symptoms and drug consumption in the previous 3 months. Allergological evaluation
      by skin-prick tests and seric-specific IgE determination for relevant local
      inhalant allergens was made. Lung function was studied evaluating expiratory
      flows and measuring lung volumes by nitrogen washout technique. One hundred
      twenty-seven of 200 (63%) children showed functional abnormalities: 21 (10.5%)
      children had flow reductions, 56 (28%) children had volume modifications, and 50
      (25%) children had either flow and lung volume alterations, respectively. We
      observed increased total lung capacity (TLC), residual volume (RV), and ratio
      RV/TLC values more often in patients with mild and moderate persistent asthma
      than in patients with intermittent asthma. No significant difference was detected
      considering expiratory flows. Measurements of lung volumes are an important tool
      to evaluate "air trapping" in asthmatic patients and this could be related to
      disease severity. According to the literature, our data suggest that an increase
      of RV, functional residual capacity RV/TLC could be the only functional airway
      dysfunction present in asthmatic children during asymptomatic period.

PMID- 16948351
TI  - The role of IL-18 in Th1/Th2 balance in children.
AB  - Interleukin (IL)-18 has been identified as a mediator inducing interferon gamma
      release from type 1 helper (Th1) cells, CD8+ T cells, and natural killer cells,
      synergizing with IL-12. Several studies report differential roles of IL-18; but
      little is known about the role of IL-18 in Th1/Th2 balance in children. The aim
      of this study was to evaluate the role of IL-18 in Th1- and Th2-mediated diseases
      of children. Serum IL-18 levels were measured in a group of patients with acute
      asthma exacerbation (n = 24), in a group of patients who had recently been
      diagnosed as type I insulin-dependent diabetes mellitus (n = 18), and in a group
      of healthy subjects (n = 20). The groups were compared with respect to IL-18
      levels. Significantly lower serum IL-18 levels were found in patients with acute
      asthma (median, 8.55 pg/mL) and insulin-dependent diabetes mellitus (median, 7.20
      pg/mL) than in control subjects (median, 140.10 pg/mL; p < 0.05 and p < 0.001,
      respectively). We suggest that IL-18 may play an immunoregulatory role in
      allergic and autoimmune diseases and decreased expression of IL-18 can shift the
      immune responses to both Th1- and Th2-mediated ways.

PMID- 16948352
TI  - T-lymphocyte activation and the levels of eosinophilic cationic protein and
      interleukin-5 in asthmatic children with acute exacerbation and effect of
      glucocorticoid treatment.
AB  - The aim of this study was to evaluate the immunologic parameters and the effects
      of glucocorticoid treatment, the absolute numbers of CD4+/CD25+ T lymphocytes,
      eosinophil counts, levels of eosinophilic cationic protein (ECP), and interleukin
      (IL)-5 in peripheral blood of patients having acute asthma exacerbations and
      healthy children were investigated. Samples for the absolute numbers CD4+/CD25+ T
      lymphocyte and eosinophil count, ECP, and IL-5 were obtained before (day 1) and
      after (day 5) glucocorticoid treatment. Forced expiratory volume in 1 second and
      peak expiratory flow rate were measured on days 1 and 5 in asthma patients (n =
      25) and in the control group (n = 15). The absolute numbers of CD4+/CD25+ T
      lymphocyte and eosinophils, levels of ECP, and IL-5 were significantly greater,
      while forced expiratory volume in 1 second and peak expiratory flow rate were
      significantly less in the patients with asthma than in the control subjects on
      day 1. These parameters normalized after glucocorticoid treatment with clinical
      improvement by day 5. Glucocorticoid treatment is associated with clinical and
      laboratory improvement achieved in patients with acute asthma exacerbations.

PMID- 16948353
TI  - Percentage of eosinophils with surface CD44 and levels of eosinophil cationic
      protein in the peripheral blood in children with bronchial asthma and their
      changes after montelukast therapy.
AB  - Bronchial asthma (BA) is chronic inflammation of the respiratory tract with a
      role played by a variety of cells, particularly mast cells, eosinophils (Eo), and
      T lymphocytes. The serum levels of Eo cationic protein (S-ECP) reflect the
      severity of bronchial inflammation and the level of bronchial hyperreactivity in
      asthma patients. One of the most important adhesion molecules is CD44. We
      examined S-ECP, the percentage of Eo with surface CD44 expression (EoCD44), and
      Eo count in the peripheral blood of newly diagnosed pediatric atopic patients
      with intermittent and persistent mild BA according to the Global Iniative for
      Asthma 2002, in a proportion of patients 3 months after initiation of montelukast
      therapy. Ninety-seven children with BA had their medical history taken, and S
      ECP, with the percentage of EoCD44 determined by direct fluorescence from whole
      blood using flow cytometry with a Coulter EPICS XL cytometer, and Eo count, total
      serum immunoglobulin E levels (S-IgE) were determined. Therapy with montelukast
      (5 mg daily) was started in 23 children. Three months after the first collection,
      a second S-ECP level and EoCD44 count determinations were made. An inverse
      correlation between S-ECP and EoCD44 (-0.602; p < 0.0001) was found in the 97
      children with BA. In the 23 children receiving montelukast we documented inverse
      correlation of fluctuation on S-ECP and EoCD44 after 3 months. These results were
      not significant. An inverse correlation between S-ECP and percent of EoCD44 was
      established in the 97 children with asthma before therapy initiation. The lower
      percentage of EoCD44 in peripheral blood in asthmatic children is due to Eo
      inflammation activity and attests to massive Eo invasion into the airways.
      Determination of the percentage proportion of EoCD44 is another potential
      indirect marker of the multiple features of Eo inflammation.

PMID- 16948354
TI  - The effect of montelukast on soluble interleukin-2 receptor and tumor necrosis
      factor alpha in pediatric asthma.
AB  - Proinflammatory cytokines such as tumor necrosis factor (TNF) alpha and soluble
      interleukin 2 receptor (sIL-2R) are very important mediators in induction of
      inflammatory response in lung. The aim of this study was to investigate anti
      inflammatory response of cysteinyl leukotriene receptor antagonist montelukast on
      macrophage and T-cell activation by sIL-2R and TNF-alpha in mild atopic asthmatic
      children. Fifteen children with mild-to-moderate atopic asthma and 15 nonatopic
      children as control, enrolled in the study. Asthmatic children were treated with
      montelukast, 5-mg tablets, for 1 month. Lung function test forced expiratory
      volume in 1 second (FEV1) was performed before and after treatment. Serum TNF
      alpha, sIL-2R, and eosinophil cationic protein levels were determined in the
      control group and in asthmatic children before and after treatment. The mean
      eosinophil cationic protein value was significantly decreased (33.1 +/- 14.8 and
      22.2 +/- 12.1; p < 0.05) and FEV1 was significantly increased (86.9 +/- 20.9 and
      102.1 +/- 12.7; p < 0.05) after 1 month treatment with montelukast. The mean
      serum IL-2R levels were significantly higher in the before treatment group than
      in the after treatment group (1061.9 +/- 491 and 794 +/- 230.9; p < 0.05) or in
      control subjects (581.1 +/- 123; p < 0.01). The mean serum TNF-alpha level was
      higher in the before treatment group than in the after treatment group and
      control group (7.30 +/- 3.93, 5.20 +/- 1.46, and 4.95 +/- 1.27; p < 0.05). There
      was a significant correlation between TNF-alpha and sIL-2R in patients before
      montelukast treatment (r = 0.674; p < 0.01). This study indicates that
      montelukast improves clinical parameters and shows anti-inflammatory response by
      decreasing serum sIL-2R and TNF-alpha levels.

PMID- 16948355
TI  - Wild rice, hypoallergenic rice--immunologic comparison.
AB  - Rice is a cereal that is mainly produced and widely consumed in Asian countries
      including Korea. Several reports have suggested a role of IgE-mediated
      hypersensitivity in asthma and eczema associated with ingestion or inhalation of
      rice. In Japan, hypoallergenic rices are used for a substitute of common rice in
      some atopic patients. We performed this study to identify major allergens of rice
      and changed allergenicity in cooked and hypoallergenic rice. We purified crude
      extracts from a variety of rice and analyzed their protein distributions by
      sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Based on
      UniCAP test and skin-prick test, we selected sera with high sensitivity and
      analyzed specific IgE binding to rice by immunoblotting. In addition, the
      inhibition rate among some rice was determined by enzyme linked immunosorbent
      assay and CAP test. As the result of this study, rice with various origins and
      polishing levels had no difference in protein band pattern. After cooking, it was
      difficult to detect protein bands distributed in raw rice; and, even through IgE
      immunoblot analysis, it was impossible to differentiate between wild and
      hypoallergenic rice. In addition, both wild and hypoallergenic rice still had IgE
      binding activity on their remaining protein bands. In conclusion, almost all
      proteins of rice were excluded or weakened in the process of boiling and IgE
      binding activity still remained even in hypoallergenic rice.

PMID- 16948356
TI  - Buckwheat allergy.
AB  - Buckwheat, which has been abundantly consumed in Asian countries and has been
      increasingly popular in the United States, Canada, and Europe, can be a potent
      allergen when ingested or inhaled. A case is reported of a 36-year-old man who
      experienced nausea, vomiting, urticaria, a sensation of throat closing, inability
      to speak, dyspnea, and dizziness shortly after ingesting a large portion of
      buckwheat that required emergency room treatment. In the previous 2 years he had
      experienced asthma, contact urticaria, allergic conjunctivitis, and allergic
      rhinitis from sleeping with a buckwheat pillow. Six months after the first
      ingestion reaction, the patient again experienced anaphylaxis requiring emergency
      treatment when he accidentally ate crackers with a small amount of buckwheat.
      Skin-prick testing showed a strong positive response to buckwheat, and a
      radioallergosorbent assay test was highly positive to buckwheat. It is possible
      that inhaled buckwheat provoking asthma sensitized the patient before his two
      episodes of ingestion anaphylaxis. Buckwheat is a potent allergen that can induce
      various clinical manifestations in the same individual.

PMID- 16948357
TI  - Poppy seed allergy: a case report and review of the literature.
AB  - Seeds of the poppy plant are traditionally used in bakeries, e.g., for garnishing
      bread or making cakes. Reports of allergic type I sensitivity to poppy seed are
      rare. According to the literature, severe reactions may occur, affecting mainly
      patients with allergy to pollens or nuts. We report on a 16-year-old boy who has
      developed erythema and angioedema, conjunctivitis, and dyspnea due to inhalation
      of poppy seed. Skin-prick tests were positive for poppy seed, hazelnut, and
      chickpea. The concentration of specific IgE for poppy seed, hazelnut, and peanut
      were 3.36 kU/L (class 2), 1.5 kU/L (class 2), and 6.17 kU/L (class 3),
      respectively. Allergic reactions associated with inhalation of food allergens
      have been reported for some foods but not for poppy seed. This is the first
      report on inhalative allergy to the poppy seed. Although poppy seeds are not
      commonly used, we underline the possible importance of such rare and often hidden
      sources of allergens, especially in patients with nut allergy.

PMID- 16948358
TI  - IgE-mediated sensitization in seafood processing workers.
AB  - Occupational-related allergic sensitization has been reported in fishery workers.
      The aim of this study was to investigate the prevalence, work-related symptoms,
      and possible risk factors in this occupationally exposed population in Greece.
      Sixty-four fish and seafood processing workers were compared with 60 controls
      regarding sensitization to seafood allergens. All participants underwent skin
      prick tests (SPTs) with cod, sardines, shrimp, spiny lobster, crabs, salmon,
      mussels, and trout plus negative and positive control. The level of specific IgE
      (radioallergosorbent test) was evaluated in subjects with positive SPTs.
      Sensitization criteria were both SPTs and the corresponding positive
      radioallergosorbent test. Atopic status was tested with SPTs to seven common
      inhalant allergens. Potential risk factors for IgE sensitization were
      investigated using logistic regression analysis. Twenty-three of 64 workers
      (35.9%) were sensitive to at least one of the seafood allergens tested, and the
      prevalence in the control group was 10% (6/60; odds ratio, 5.049; 95% CI, 1.884
      13.533). The prevalence of sensitization in allergen species tested in the
      fishery workers group was shrimp, 12.5%; spiny lobster, 10.9%; mussels, 7.8%;
      crabs 3.1%; cod, 3.1%; sardines, 1.6%; salmon, 1.6%; and trout, 1.6%. Presence of
      atopy (p = 0.02), intensity (p = 0.03), and duration of exposure (p = 0.03) was
      found as potential risk factors for IgE sensitization. Four of 64 (6.25%) workers
      reported work-related symptoms. Occupational exposure to fish and seafood
      significantly increases the likelihood of sensitization in seafood allergens and
      atopy, duration, and intensity of exposure may represent potential risk factors
      in seafood processing workers.

PMID- 16948359
TI  - Assessment of mid flow rate measurements in patients undergoing methacholine
      challenge.
AB  - The objective of this study is to assess the FEF(25-75) and FEF(25-75)/FVC in
      relation to the FEV1 in patients who have had a methacholine inhalation challenge
      study for a variety of clinical indications. The study is a retrospective review
      of methacholine challenge results at the university medical center. One hundred
      twenty-one consecutive patients who had a methacholine challenge performed for
      clinical indications were included in the study with no intervention.
      Methacholine was administered in successively increasing twofold concentrations
      in doses from 0.62 mg to a final concentration of 10 mg. A 20% drop in FEV1
      compared to the prechallenge value was considered a positive test. We considered
      > or = 25% decrease in FEF(25-75) as a significant change. The > or = 25%
      decrease in FEF(25-75) occurred sooner than the 20% drop in FEV1 with a positive
      response occurring at least one full dose sooner in 23 of the 55 subjects. Thirty
      two subjects reacted at the same dose. The dose at which the FEF(25-75) decreased
      by > or = 25% was significantly different from the corresponding dose causing a
      20% decrease in FEV1. The FEF(25-75) decreases more per mg methacholine. There
      were no subjects in whom there was > or = 20% decrease in FEV1 without a > or =
      25% decrease in FEF(25-75). The mean FEF(25-75)/FVC after diluent inhalation =
      0.87 +/- 0.27 standard deviation with a range of 0.23 to 1.67. The doses at which
      the FEF(25-75)/FVC decreased by > or = 20% and by > or = 30% was significantly
      lower than the corresponding doses causing a 20% decrease in FEV1. FEF(25-75) and
      the FEF(25-75)/FVC are more sensitive but less specific than the FEV1 as
      indicators of a positive response to a methacholine challenge. The FEF(25-75)/FVC
      does not provide additional information to that provided by the FEF(25-75).

PMID- 16948360
TI  - Vocal cord dysfunction.
AB  - A case of vocal cord dysfunction (VCD) is presented, followed by a discussion of
      the clinical characteristics, pathogenesis, diagnosis, and management of this
      disorder. Special emphasis is given to clinical pearls and pitfalls for the
      practicing allergist. VCD is a common condition that mimics asthma. Dyspnea,
      cough, and chest tightness are frequent manifestations of the disease. A high
      degree of clinical suspicion is required to recognize VCD and diagnosis is made
      most confidently by laryngoscopy. The mainstay of treatment for VCD is
      reassurance, speech therapy, and treatment of associated comorbidities including
      gastroesophageal reflux disease, postnasal drip syndrome, and psychiatric
      conditions.

PMID- 16948361
TI  - Nursing faculty members competence of Web-based course development systems
      directly influences students' satisfaction.
AB  - Nursing faculty are compelled to use and implement computer assisted instruction
      to meet the technological needs of a diverse student population. Much of the
      current trend of nursing faculty and nursing curricula design encompasses a
      traditional face-to-face instruction mode and teaching methodology. Although
      faculty are using and implementing computer assisted instruction, the format is
      not personalized to the student. The goal of enhancing and maintaining continued
      student satisfaction will depend on the efficient nature of the faculty in the
      development of their individual technological competencies, nursing content area
      mastery and available university-wide technological support systems and
      resources.

PMID- 16948362
TI  - Cutting edge technology to enhance nursing classroom instruction at Coppin State
      University.
AB  - Educational technologies have changed the paradigm of the teacher-student
      relationship in nursing education. Nursing students expect to use and to learn
      from cutting edge technology during their academic careers. Varied technology,
      from specified software programs (Tegrity and Blackboard) to the use of the
      Internet as a research medium, can enhance student learning. The authors provide
      an overview of current cutting edge technologies in nursing classroom instruction
      and its impact on future nursing practice.

PMID- 16948363
TI  - Retaining and assisting nontraditional nursing students in a baccalaureate
      nursing program utilizing Blackboard & Tegrity technologies.
AB  - Historically Black College and University (HBCU) implemented new teaching
      methodologies that incorporate both technology and face-to-face teaching as a
      means of assisting and retaining the non-traditional student. Teaching strategies
      were enhanced through a new instructional delivery method, Tegrity. The course,
      Introduction to Nursing Process I, was transformed to a hybrid on-line course
      using Blackboard and Tegrity. Its transformation reflected inherent strengths
      when faculty used a systematic approach and implemented a strong team effort. A
      team approach including collaboration on lecture content and shared PowerPoint
      presentations in all sections of the course facilitated consistency in the course
      content. A conceptual model, which included a systems approach that encourages
      student involvement, was actualized throughout the project. This article utilizes
      a descriptive approach and explains what faculty did to retain and assist the 157
      newly admitted non-traditional baccalaureate nursing students using two
      technological methods.

PMID- 16948364
TI  - Integration of technology in a clinical research setting.
AB  - The use of wireless technology to collect and retrieve relevant patient data has
      been in use on many nursing units for the past decade. The technology continues
      to advance as it relates to patient data collection devices. The utilization of
      computers (in the form of a wireless tablet) is used in the General Clinical
      Research Unit (GCRC) at Howard University Hospital. The wireless technology is
      used for the compilation and retrieval of pertinent research data.

PMID- 16948365
TI  - Family nurse practitioner students utilization of Personal Digital Assistants
      (PDAs): implications for practice.
AB  - Personal Digital Assistants (PDAs) are a readily accessible source of information
      to aid in the delivery of patient care. A pilot group of five Family Nurse
      Practitioner students used PDAs to organize data and access information relevant
      to patient care. Utilization of the PDAs in the clinical setting provided
      practice guidelines, textbook information and protocols that were readily
      accessible. The PDA made it possible for students to utilize preexisting
      knowledge with additional learning resources. The PDAs were purchased with funds
      provided from a United States Department of Health and Human Services, Health
      Resources and Services Administration (HRSA) grant.

PMID- 16948366
TI  - Career of caring controls compass of life.

PMID- 16948367
TI  - Breast-feeding and other mother-child factors associated with developmental
      enamel defects in the primary teeth of Brazilian children.
AB  - PURPOSE: The purpose of this study was to examine the association between
      developmental defects in the enamel (DDE) of the primary teeth and low birth
      weight or prematurity. METHODS: A case-control study was carried out in Itajai,
      Southern Brazil, involving 3- to 5-year-old children. The case group was composed
      of 102 children presenting at least 1 dental surface with DDE. The control group
      comprised 113 children without DDE matched by sex and age and enrolled in the
      same day care centers. All teeth were clinically examined using the Modified
      Index of Developmental Defects of Enamel. The outcome variable of the study was
      DDE in at least 1 dental surface, and the independent variables were: (1) birth
      weight; (2) gestational age; and (3) breast-feeding. Maternal schooling and
      health problems of the mother during pregnancy and of the child during the first
      year of life were collected as potential confounding factors. Simple and
      conditional multiple logistic regression analyses were performed, providing crude
      and adjusted odds ratio and 95% confidence intervals. RESULTS: Prematurity
      (OR=2.6; 95% CI=1.0-6.4) and children who did not breast-feed (OR=3.2; 95% CI=1.2
      8.4) were associated with defects in tooth enamel after adjusting for possible
      confounding variables. CONCLUSIONS: In this study, premature children and those
      who did not breast-feed could be considered at risk for developing defects in
      tooth enamel.

PMID- 16948368
TI  - Comparative evaluation of endodontic management of teeth with unformed apices
      with mineral trioxide aggregate and calcium hydroxide.
AB  - PURPOSE: The purpose of this study was to compare mineral trioxide aggregate
      (MTA) and calcium hydroxide (Ca(OH)2) for their efficacies and time taken for
      formation of apical biological calcific barriers and resolution of periapical
      radiolucencies, if present at baseline, in teeth with unformed apices. METHODS:
      Twenty nonvital permanent maxillary incisors with unformed apices, stratified
      according to the size of periapical radiolucencies and stage of root development,
      were equally allocated to MTA and Ca(OH)2 groups. In group 1 (MTA group), after 7
      days of disinfection with Ca(OH)2, MTA was packed into the apical one third of
      the root canals and obturation with gutta percha (GP) was performed in 90% (9/10)
      of cases within 15 to 30 days. In group 2 (Ca(OH)2 group), obturation was
      performed following clinical and radiographic depiction of the apical stop.
      RESULTS: The mean time taken for apical biological barrier formation was 3 +/-
      2.9 months for group 1 and 7 +/- 2.5 months for group 2 (P=.008). The periapical
      radiolucencies were resolved in 4.6 +/- 1.5 months for group 1 and 4.4 +/- 1.3
      months for group 2 (P=.83). The total treatment was completed in 0.75 +/- 0.4859
      months and 7 +/- 2.5 months for groups 1 and 2, respectively. CONCLUSION: The 2
      materials were found to be equally efficacious in the management of nonvital
      teeth with unformed apices. Time taken to complete the treatment and the
      biological barrier formation in group 1 was significantly less than that for
      group 2. The healing time for periapical radiolucencies was almost identical.

PMID- 16948369
TI  - Effect of active pretreatment of self-etching primers on the ultramorphology of
      intact primary and permanent tooth enamel.
AB  - PURPOSE: The objective of this study was to evaluate the ultramorphological
      changes after agitated and nonagitated application of self-etching primer systems
      on unground primary and permanent enamel. METHODS: Five self-etching primer
      systems were used: (1) Clearfil SE Bond; (2) Clearfil Protect Bond; (3) Adper
      Prompt; (4) Xeno III; and (5) nonrinse conditioner (NRC). Noncarious human
      primary and permanent incisors were collected and stored frozen until used.
      Intact labial surfaces were divided into 2 halves, applying the self-etching
      primers with (active application) and without (inactive agitation) using a
      microbrush within the times recommended by the manufacturers. Treated surfaces
      were further processed for ultramorphological evaluation under scanning electron
      microscope (SEM). RESULTS: All tested self-etching systems produced weaker etch
      patterns and less dissolution of enamel surface compared with acid-etched samples
      in both primary and permanent teeth. Except for NRC and Adper Prompt, agitation
      of the surface did not increase the etching efficacy. Clearfil SE Bond and
      Clearfil Protect Bond resulted in similar morphological features following
      application in either mode. CONCLUSION: While agitation of self-etching primers
      may improve etching efficacy, this effect appears to be dependent on the material
      used. Phosphoric acid produces well-defined etching patterns on intact primary
      and permanent enamel.

PMID- 16948370
TI  - Clinical evaluation of atraumatic restorations in primary molars: a comparison
      between 2 glass ionomer cements.
AB  - Dental caries continues to be a highly prevalent disease among Brazilian
      preschoolers, especially those with low socioeconomic status. The purpose of this
      randomized, controlled trial was to evaluate in vivo 245 simplified restorations
      in deciduous molars using glass ionomer cements (Vidrion R and Ketac-Molar).
      Dental restorations were evaluated at 6- and 12-month follow-ups. The teeth
      restored with Vidrion R (SS White) on a single tooth surface were successful in
      87% of the cases evaluated at 6 months and in 63% at 12 months. The teeth
      restored with Ketac-Molar on one surface achieved a success rate of 95% at 6
      months and 82% at 12 months. No recurrent caries or pulpal infection was evident.
      Logistic regression analysis demonstrated that teeth with cavities restricted to
      the occlusal surface on sclerotic dentin showed the best adhesion to the
      restorative material. The restorations with Ketac-Molar had a better clinical
      performance than those with Vidrion R.

PMID- 16948371
TI  - Child temperament and risk factors for early childhood caries.
AB  - PURPOSE: The purpose of this study was to determine if a relationship existed
      between a mother's perception of her child's temperament and the child's risk
      factors for early childhood caries (ECC). METHODS: Data was collected from 629
      records of children ages 0 to 4 who were patients of the University of Iowa's
      Infant Oral Health Program. Data included: (1) maternal report of child's
      temperament; (2) knowledge of ECC; (3) dietary and oral hygiene habits; and (4)
      clinical evidence of cavitated and noncavitated lesions and visible plaque on
      maxillary incisors. Chi-square tests and logistic regression models were used to
      analyze the data. RESULTS: Bivariate analyses showed that children reported as
      "easy" were more likely to: (1) be younger (P=.001); (2) be breast-fed to sleep
      (P=.046); (3) be breast-fed throughout the night (P=.012); and (4) have their
      teeth brushed twice daily (P=.006). Children reported as "difficult" were more
      likely to: (1) be bottle-fed to sleep (P=.002); and (2) have noncavitated lesions
      (P=.044). Final logistic regression analysis indicated that children perceived as
      "easy" were more likely to breast-fed throughout the night (odds ratio [OR]=
      1.77; P=.016), while those perceived as "difficult" were more likely to be bottle
      fed to sleep (OR=1.74; P=.016). CONCLUSIONS: Maternal reported child temperament
      may be related to important early childhood caries risk factors.

PMID- 16948373
TI  - Management of an unusual maxillary dentoalveolar fracture: a case report.
AB  - The purpose of this case report was to describe the management of a trauma
      induced maxillary dentoalveolar fracture of the right maxilla in an 8-year-old
      boy. The child presented with swelling of the right maxillary region, difficulty
      in chewing and closing the mouth, and a sutured laceration on the cheek. Complete
      palatal displacement of the fractured fragment involving the deciduous canine and
      molars was observed clinically and confirmed by radiological examination. The
      fracture was reduced and stabilized using a custom-fabricated, open-cap acrylic
      splint with modified interdental wiring under general anesthesia.

PMID- 16948372
TI  - Association of maternal-child characteristics as a factor in early childhood
      caries and salivary bacterial counts.
AB  - The aim of this study was to investigate the caries-related microorganisms in
      saliva and the prevalence of Early childhood caries (ECC) in 15- to 35-month-old
      Turkish children and their associations with the characteristics of the mothers,
      socioeconomic criteria, and feeding habits of the children. METHODS: Saliva
      samples of 101 children were studied to determine the numbers of Streptococcus
      mutans, lactobacilli, and Candida albicans. A questionnaire regarding the
      characteristics of the mothers, socioeconomic criteria, and feeding habits of the
      children was carried out before the dental examinations of the mother-child
      pairs. RESULTS: The regression analyses revealed DMFS scores of the mothers as an
      impact factor for the children's caries experience. The prolonged usage of
      feeding bottle with sweetened milk, pacifier use, and maternal sharing were
      strongly associated with the colonization of S. mutans, lactobacilli, and C.
      albicans, respectively. A significant correlation was also found between maternal
      education and S. mutans. CONCLUSION: Data indicated that the mother's DMFS
      scores, education, and feeding habits were strong risk indicators for the
      colonization of caries-related micro-organisms and ECC.

PMID- 16948374
TI  - Children's preferences concerning the physical appearance of dental injectors.
AB  - PURPOSE: This pilot study was carried out to assess how the physical appearance
      of dental injectors influenced children's choice. METHODS: The study group
      consisted of 34 randomly selected children (17 boys, 17 girls) between the ages
      of 7 and 11 (mean age=8.6 +/- 1.4), who had been registered for treatment at the
      School of Dentistry, Marmara University. A combination of tests-the Children's
      Fear Survey Schedule-Dental Subscale (CFSS-DS), Venham Picture Test (VPT), and
      facial image scale (FIS)-were used to assess the multi-dimensional character of
      children's dental anxiety. Dental injectors (Wand, Citoject, traditional metal
      injector [MI], and plastic injector [PI]) were displayed on a tray and introduced
      to the children. The children were asked to consider which injectors they would
      choose "if their tooth had to be put to sleep," and their preferences were noted
      starting with their first choice. RESULTS: The children's first choice was: (1)
      the Wand (56%); (2) PI (29%); (3) Citoject (12%); and (4) MI (3%). The anxious
      children (n= 13) preferred the Wand with significantly higher ratings (Wand=84%;
      Citoject=8%; MI=8%; PI=0%). CONCLUSION: The physical appearance of dental
      injectors is important to children and even more important for children who are
      anxious.

PMID- 16948376
TI  - They are more than just pretty people handing out cool pens.

PMID- 16948375
TI  - Comparison of marginal microleakage of flowable composite restorations in primary
      molars prepared by high-speed carbide bur, Er:YAG laser, and air abrasion.
AB  - PURPOSE: The purpose of this study was to assess in vitro the influence of 3
      cavity preparation devices (carbide bur, Er:YAG laser, and air abrasion) on the
      microleakage of flowable composite restorations in primary teeth. METHODS:
      Fifteen primary second molars were selected, and Class V cavities were prepared
      on the buccal/lingual surfaces, being assigned to 3 groups (n= 10). Group 1
      (control) was prepared using a high-speed handpiece and was acid etched. Group 2
      was prepared and treated with a Er:YAG laser (400mJ/4Hz and 80mJ/4Hz,
      respectively) and was acid etched. Group 3 was prepared and treated with an air
      abrasion system and was acid etched. Cavities were restored and stored for 7
      days. Restorations were polished, thermocycled, immersed in 0.2% rhodamine B,
      sectioned, and analyzed for leakage. RESULTS: Er:YAG laser-prepared cavities
      showed the highest degree of infiltration. The performance of the air abrasion
      device was comparable to that of the high-speed handpiece. CONCLUSION: It may be
      concluded that the method of cavity preparation affected the microleakage of
      Class V cavities restored with flowable composite in primary teeth.

PMID- 16948377
TI  - Recognizing a new public health concern.

PMID- 16948378
TI  - Cutaneous leiomyomas: a clinical marker of risk for hereditary leiomyomatosis and
      renal cell cancer.

PMID- 16948379
TI  - The causes of acne: a qualitative study of patient perceptions of acne causation
      and their implications for acne care.

PMID- 16948380
TI  - What's your assessment? Dyshidrotic eczema.

PMID- 16948381
TI  - Specialized education for patients with psoriasis: a patient survey on its value
      and effectiveness.

PMID- 16948382
TI  - Update on preparing for the next influenza pandemic.
AB  - While previous pandemics have taken the world by surprise, the present situation
      has given the world advanced warning and a rare opportunity to prepare for the
      next pandemic. WHO urges all countries to take action now to assess their level
      of preparedness, identify priority needs, and develop a national influenza
      preparedness plan. If containing or delaying the spread of a new human influenza
      strain is possible, it will take rapid, massive coordinated global and national
      actions. The success of these actions will depend on the preparations made in
      advance by each member of the international community.

PMID- 16948383
TI  - Of primary importance.

PMID- 16948384
TI  - Guttate psoriasis.

PMID- 16948385
TI  - Pityriasis rosea.

PMID- 16948386
TI  - Intracorneal hemorrhage.

PMID- 16948388
TI  - Streamlining adverse event reporting in trials.

PMID- 16948387
TI  - Benign neoplasms/hyperplasia.

PMID- 16948389
TI  - Megatrends, the annual report, possibilities.
AB  - The successful leader and manager have two very important challenges: to scan the
      horizon and not be thrown into crisis by not seeing predictable surprises, and to
      recognize the longer, more pervasive trends that are in the more distant future.
      In reality, these two processes merge and drive the future planning of the
      patient care enterprise. The merger of the operational imperatives and the long
      range trends that create very different ways for us to work is the work of
      leaders. In the words of Senge and colleagues (2004), we are at the end of the
      era of hierarchical leadership and at the beginning of distributed, shared
      networks where "...becoming a real human being really is the primary leadership
      issue of our time" (p. 186). As we finish a year and begin a new one, it is time
      to look backward, look forward, and "see" the new world. We must also look into
      ourselves to see the inner work we need to do to meet the challenges of the next
      5 years.

PMID- 16948393
TI  - Employment form I-9 changes.

PMID- 16948394
TI  - Osteoporosis: how should it be treated?
AB  - Osteoporosis develops as a result of imbalance between bone resorption and bone
      formation. A number of effective and safe therapies for osteoporosis are
      currently available, most of which are inhibitors of bone resorption. However,
      because osteoporosis is a complex and heterogeneous disease with different
      pathogenetic factors, defining the role of the different factors in its
      development is important in formulating a more selective approach to therapy.
      This review discusses the advantages and disadvantages of the currently available
      agents used in the management of osteoporosis.

PMID- 16948395
TI  - Atherosclerosis: immune and inflammatory aspects.
AB  - This review article discusses the historical origin of our continuously evolving
      model of the etiology of atherosclerotic cardiovascular disease. The basic
      molecular biologic concepts underlying the development of coronary artery disease
      and the dynamic connection between the immune system and arterial integrity are
      explored. Emphasis is placed on the role of inflammation as a driving force in
      the process of atherosclerosis and vascular endothelium as a modulating factor in
      the pathogenesis of coronary artery disease.

PMID- 16948397
TI  - Does diabetes mellitus explain the higher hospital mortality of women with acute
      myocardial infarction? Results from the Berlin Myocardial Infarction Registry.
AB  - BACKGROUND: Women with acute myocardial infarction (AMI) exhibit greater hospital
      mortality than do men. In general, diabetes mellitus is one of the major factors
      influencing the outcome of patients with AMI. The aim of this study was to
      analyze the interaction between diabetes and gender, specifically with regard to
      the higher hospital mortality of female AMI patients aged < or = 75 years.
      METHODS: We prospectively collected data from 3,715 patients aged < or = 75
      (2,794 men, 921 women) with acute myocardial infarction who were treated in 25
      hospitals in Berlin, Germany, from 1999 to 2002. In a multivariate analysis, we
      specifically studied the interaction between the factors diabetes mellitus and
      gender in their effects on hospital mortality. RESULTS: After adjustment in
      multivariate analysis, the interaction between gender and diabetes was
      statistically significant, and the estimated odds ratios were as follows: female
      diabetic patients compared with male diabetic patients, odds ratio (OR) = 2.28
      (95% confidence interval [CI] 1.42-3.68); female diabetic patients compared with
      male nondiabetic patients, OR = 2.90 (95% CI 1.90-4.42); and female diabetic
      patients compared with female nondiabetic patients, OR = 2.92 (95% CI 1.75-4.87).
      There was no statistically significant difference between the risk of dying for
      female nondiabetic patients or for male diabetic patients when compared with male
      nondiabetic patients. CONCLUSIONS: In AMI patients aged < or = 75 years, female
      gender alone is not an independent predictor of hospital mortality. Detailed,
      multivariate analysis reveals that specifically diabetic women demonstrate higher
      hospital mortality than do men. Special attention should be provided to these
      female diabetic patients.

PMID- 16948396
TI  - Role of the mitogen-activated protein kinases in cytokine-mediated inhibition of
      insulin gene expression.
AB  - BACKGROUND: Following islet transplant, inflammatory cells in the vicinity of the
      transplant graft elaborate cytokines that contribute to islet graft dysfunction.
      To better understand the mechanism for this effect of cytokines on graft
      function, we examined the impact of cytokines on intracellular signaling and
      insulin promoter activity in pancreatic beta cells. METHODS: Two pancreatic beta
      cell lines, RINm5F and MIN6 cells, were transfected with a rat insulin promoter
      (RIP) luciferase fusion gene and treated with a combination of cytokines,
      including 5 ng/mL interleukin-1beta + 10 ng/mL tumor necrosis factor alpha + 25
      ng/mL interferon-gamma. The effect of cytokines on beta cell transcription
      factors and signaling pathways was analyzed by real-time reverse transcriptase
      polymerase chain reaction and Western blotting. RESULTS: Treatment for 48 hours
      with the combination of cytokines decreased insulin 1 messenger ribonucleic acid
      (mRNA) levels to 51% and 38% and RIP1 activity to 16% and 30% of control levels
      in RINm5F and MIN6 cells, respectively. The level of mRNAs encoding transcription
      factors important for insulin gene expression and beta cell function, including
      MafA, PDX-1, Nkx6.1, and Pax6, was also decreased by cytokine treatment.
      Cytokines increased phosphorylation of ERK and c-Jun NH2-terminal kinase (JNK) in
      RINm5F and MIN6 cells but had no effect on p38 kinase phosphorylation. Neither
      JNK nor ERK inhibition had a significant effect on cytokine-mediated inhibition
      of RIP1 activity. CONCLUSION: Beyond modulating beta cell survival, cytokines
      inhibit insulin promoter activity, which likely contributes to islet dysfunction
      following islet transplant. This effect appears to be mediated, in part, via
      altered expression of transcription factors important for insulin gene
      expression.

PMID- 16948398
TI  - Soft-tissue grafting to improve long-term success of dental implants.

PMID- 16948399
TI  - A literature review on Complementary and Alternative Medicine for the treatment
      of breast cancer: Hawai'i.
AB  - The purpose of this literature review is to survey the scholarly work done in the
      field of Complementary and Alternative Medicine (CAM) as it relates to breast
      cancer treatment, accenting studies done on diverse ethnicities of Hawai'i. This
      study reviews articles published in biomedical literature from 1999-2005 that
      report findings related to the themes recognized in this area of study.

PMID- 16948401
TI  - Simulation in medical education--SimTiki.

PMID- 16948400
TI  - The use of Complementary and Alternative Medicine by Asian women of Hawai'i in
      the treatment of breast cancer.
AB  - This qualitative investigation examined complementary and alternative medicine
      (CAM) by Hawai'i Asian women breast cancer survivors. The majority of
      participants felt that the conventional treatment they received was adequate in
      treating their cancer but was impersonal in nature leaving them feeling
      abandoned. Many sought CAM to improve their quality of life. Additional research
      on CAM and the patient-physician relationship is urgently needed.

PMID- 16948402
TI  - Hawaii Colorectal Cancer Family Registry.

PMID- 16948403
TI  - Issues in medical malpractice I.

PMID- 16948404
TI  - Campaign meets and exceeds goal of saving 100,000 lives.

PMID- 16948405
TI  - Sept. 1 deadline nears to help shape health system reform recommendations.

PMID- 16948406
TI  - The time has come to seriously address health care reform.

PMID- 16948407
TI  - The ethics of epidemics--when healing puts the doctor's life in danger.

PMID- 16948409
TI  - Scientific research enhances quality of life for Iowans.

PMID- 16948410
TI  - Asset protection 101.

PMID- 16948411
TI  - IMS supports certificate of merit and compassionate statement legislation.

PMID- 16948412
TI  - Medical negligence & the locality rule--"That's how medicine is practiced here".

PMID- 16948413
TI  - Governor signs "I'm sorry" legislation.

PMID- 16948414
TI  - CME a vital link to state-of-the-art care.

PMID- 16948415
TI  - Crucial conversations: tools for talking when the stakes are high.

PMID- 16948416
TI  - [Difficult access to emergency care: an indication of the crisis state of
      healthcare?].

PMID- 16948417
TI  - [Access to prehospital medical care: organization and utility of the chain of
      survival].
AB  - In order to be effective, access to prehospital care must be integrated into a
      system described as "the chain of survival". This system is composed of 5
      essential phases: 1) basic help by witnesses; 2) call for help; 3) basic life
      support; 4) professional rescue and transport to the appropriate institution and
      5) access to emergency ward and hospital management. Each phase is characterized
      by a specific organization, dedicated skills and means in order to increase the
      level of care brought to the patient. This article describes the organization,
      the utility and the specificity of the chain of survival allowing access to
      prehospital medical care in the western part of Switzerland.

PMID- 16948418
TI  - [Emergency department overcrowding: a legitimate reason to refuse access to
      urgent care for non-urgent patients?].
AB  - Non-urgent cases represent 30-40% of all ED consults; they contribute to
      overcrowding of emergency departments (ED), which could be reduced if they were
      denied emergency care. However, no triage instrument has demonstrated a high
      enough degree of accuracy to safely rule out serious medical conditions: patients
      suffering from life-threatening emergencies have been inappropriately denied
      care. Insurance companies have instituted financial penalties to discourage the
      use of ED as a source of non-urgent care, but this practice mainly restricts
      access for the underprivileged. More recent data suggest that in fact most
      patients consult for appropriate urgent reasons, or have no alternate access to
      urgent care. The safe reduction of overcrowding requires a reform of the
      healthcare system based on patients' needs rather than access barriers.

PMID- 16948419
TI  - [Access of elderly patients in the emergency department: demographic evolution
      and ethical perspectives].
AB  - Due to actual demographic evolution, emergency departments have to face a
      dramatic increase in admissions of elderly people. The peculiar medical and socio
      demographic characteristics of these old patients emphasize the need of specific
      decision processes and resources allocation. An individual-based approach,
      related to significant ethical values, should allow better diagnostic and
      therapeutic attitudes. Such a way to admit, evaluate and treat older patients
      implies an active collaboration with patients and their relatives, but also with
      all medical interveners, including in particular primary care physicians.

PMID- 16948420
TI  - [Hospitalisation criteria for the acute abdominal pain patient seen at home or in
      an ambulatory setting].
AB  - Dealing at patient's home with an acute abdominal pain may be particularly
      challenging for the primary care physician. In such a clinical situation, the
      part of laboratory and radiological investigations is increasing in the
      diagnostic process. The decision to keep the patient at home based on a clinical
      evaluation alone may represent a great medical responsibility for the physician.
      Emergency departments (ED) are of course in charge of investigating such patients
      with a wide panel of investigation techniques. But these structures are
      chronically overcrowded resulting frequently in long and difficult periods of
      waiting. Based on a literature review, a description of useful clinical symptoms
      and signs is summarized and should help the decision process for the orientation
      of the patient.

PMID- 16948421
TI  - [An efficient example of a Swiss pre-hospital chain of survival: the state of
      Vaud model].
AB  - The state of Vaud model of the pre-hospital chain of survival is an example of an
      efficient way to deal with pre-hospital emergencies. It revolves around a
      centrally located dispatch center managing emergencies according to specific key
      words, allowing dispatchers to send out resources among which we find general
      practitioners, ambulances, physician staffed fast response cars or physician
      staffed helicopters and specific equipment. The Vaud pre-hospital chain of
      survival has been tailored according to geographical, demographical and political
      necessities. It undergoes constant reassessment and needs continuous adaptations
      to the ever changing demographics and epidemiology of pre-hospital medicine.

PMID- 16948422
TI  - [Preventive medicine in emergency centres: an opportunity of partnership for
      emergency physicians and primary care physicians].
AB  - Whereas preventive interventions for primary care physicians are now well
      established, the preventive interventions in emergency departments have been only
      partially and recently evaluated. Emergency departments probably represent
      however an opportunity for preventive medicine. Indeed, the population, sometimes
      vulnerable, consulting emergency departments, frequently presents risks factors
      and risks behaviours. Moreover, the concept of "teachable moment" and the studies
      recently performed seem to confirm this hypothesis. This article review the
      currently preventive interventions recommended in emergency departments and
      discuss the rationale to implement preventive medicine in emergency departments
      and the limits of this process.

PMID- 16948424
TI  - [Stem cells: the veto of George W. Bush].

PMID- 16948423
TI  - [Treatment of bone metastases with bisphosphonates].
AB  - Bone metastasis are very common in many cancers; metastatic bone disease is the
      most common cause of cancer pain and also of serious complications, which reduce
      the quality of life of these patients. Management of skeletal cancer involves a
      multimodality approach who include bisphosphonates, which in association with
      anti-tumour treatments reduce the apparition of new skeletal-related events (SRE)
      and prolong the delay to first SRE. They although reduce the pain of bone
      metastasis. All this facts do the quality of life better.

PMID- 16948425
TI  - [Zinedine Zidane-suspended for his part in World Cup head-butting].

PMID- 16948426
TI  - [Destruction of the smallpox virus: the WHO plays for time again].

PMID- 16948427
TI  - Measurements of NO2, SO2, O3, benzene and toluene using differential optical
      absorption spectroscopy (DOAS) in Shanghai, China.
AB  - NO2, SO2, O3, benzene, and toluene were measured in Taopu industry park of
      Shanghai during the period June to August 2003 by differential optical absorption
      spectroscopy (DOAS) technique. The daily average concentrations of SO2, NO2, and
      O3 ranged from 5.7 ppb to 40 ppb, 22 ppb to 123 ppb, and 10.6 ppb to 23 ppb
      respectively. SO2 and NO2 concentrations were found to depend on wind direction.
      The diurnal variation of NO2 concentrations had two peaks due to traffic
      emission. Our DOAS measurements of NO2, SO2 and O3 were compared with the
      conventional measurement instruments (API automatic monitoring instrument). The
      concept of a percent difference (PD) and linear regression methods were employed
      to study the difference between DOAS and API instruments. The correlation
      analysis between PD values and meteorological parameters and analysis of abnormal
      higher absolute PD values indicated that the lower visibility induced the bad
      compatibility between the two systems. The results showed that both systems
      exhibited strong compatibility with good correlation, therefore the DOAS system
      is able to provide reliable information on distribution patterns of major air
      pollutants. Average benzene and toluene concentrations were 1.4 and 8.0 ppb
      respectively.

PMID- 16948428
TI  - Aragonite in Roman wall paintings of the VIII(a) Regio, Aemilia, and X(a) Regio,
      Venetia et Histria.
AB  - In the Roman wall paintings different white colours were used, named Paraetonium,
      Melinum, Anularia, Eretria, Argentaria, etc. FTIR, Raman spectroscopy and X-Ray
      diffraction were applied to study different white pigments, such as calcite,
      aragonite, dolomite and huntite, white carbonates present in archaeological
      findings from Roman walls in the Mediterranean region. This study showed that it
      is possible to distinguish and identify these components in white colours. About
      450 samples of Roman wall paintings were analysed and it was observed that often
      aragonite is associated to precious coloured pigments. On the basis of the
      obtained results some considerations about the period in which the different
      kinds of white pigments were used are proposed.

PMID- 16948429
TI  - A preliminary investigation of total organic carbon variation in influent and
      effluent of Isfahan (Iran) water treatment plant, urban network and Fellman
      wells.
AB  - In this work a series of total organic carbon (TOC) analyses were carried out to
      analyse the influent and the effluent of a water treatment plant providing
      Isfahan city in Iran. Other analyses were focused on the determination of TOC in
      the urban network and Fellman wells (in Isfahan and Dehaghan cities), in order to
      compare the water quality soon after the treatment with that of circulating water
      in the city network. Since it supplies water treatment plant, TOC content of
      Zayandehrood River was also compared with the treated water. The obtained results
      revealed that there were significant differences between TOC content of effluent
      of water treatment plant and that of the urban network (made with eight different
      points). In this project all the samples were withdrawn during 2005. It is worth
      noting that the analyses were carried out with a high precision combustion
      infrared method with a confidence limit lower than 0.05. The mean of TOC in
      Isfahan and Dehaghan Fellman wells were 0.7 and 2.6 mg.l(-1), respectively. The
      mean of TOC in influent of water treatment plant during June, July and September
      were 0.703, 1.148, 1.513 mg.l(-1) respectively which after treatment process
      reduced to about 0.7 mg.l(-1). In conclusion it can be said that during the
      summer with higher consumption of water and increase in vaporizing surface
      waters, we have accumulation of organic compounds and therefore we have increase
      in TOC content of various waters.

PMID- 16948430
TI  - Dioxouranium(VI)--carboxylate complexes. Interaction with dicarboxylic acids in
      aqueous solution: speciation and structure.
AB  - In this paper we report the results of an investigation performed by
      potentiometric (H+-glass electrode) and visible spectrophotometric measurements
      on the interaction of UO2(2+) ion towards some carboxylic ligands (acetate,
      malonate, succinate, azelate). The measurements were carried out at T= 25 degrees
      C in different ionic media (KNO3 and NaCl) at different ionic strengths (0.1 < or
      = I/mol L(-1) < or = 1.0, NaCl; I/mol L(-1) = 0.1, KNO3). The dependence on ionic
      strength of formation constants was taken into account by using both a simple
      Debye-Huckel type equation and the SIT (Specific ion Interaction Theory)
      approach. Different speciation models (depending on concentration of reagents,
      ionic strength, pH-range) both for different carboxylates and different ionic
      media have been obtained. Linear combinations between formation constants,
      stoichiometric coefficients and length of alkyl chain of dicarboxylates have been
      observed and predicted formation constants at I= 0 mol L(-1) are reported for the
      interaction of UO2(2+) with HOOC-(CH2)n-COOH with 1 < or = n < or = 7. Finally, a
      visible absorption spectrum for each complex reaching a significant percentage of
      formation in solution (KNO3 medium) has been calculated to characterise the
      compounds found by pH-metric refinement.

PMID- 16948431
TI  - Construction and performance characterization of ion-selective electrodes for
      potentiometric determination of pseudoephedrine hydrochloride applying batch and
      flow injection analysis techniques.
AB  - New pseudoephedrine selective electrodes have been constructed of the
      conventional polymer membrane type by incorporation of pseudoephedrine
      phosphotungstate (PE-PT) or pseudoephedrine-silicotungstate (PE-SiT) ion
      associates in a poly vinyl chloride (PVC) membrane plasticized with dibutyl
      phthalate (DBP). The electrodes were fully characterized in terms of the membrane
      composition, temperature, and pH. The electrodes exhibited mean slopes of
      calibration graphs of 57.09 and 56.10 mV concentration decade(-1) of PECl at 25
      degrees C for (PE-PT) and (PE-SiT) electrodes, respectively. The electrodes
      showed fast, stable, and near-Nernstian response over the concentration ranges
      6.31 x 10(-6)-1.00 x 10(-2) and 5.00 x 10(-5)-1.00x10(-2) M in the case of PE-PT
      applying batch and flow injection (FI) analysis, respectively, and 1.00 x 10(-5)
      1.00 x 10(-2) and 5.00 x 10(-5)-1.00x10(-2) M in the case of PE-SiT for batch and
      FI analysis system, respectively. Detection limit was 5.01x 10(-6) M for PE-PT
      electrode and 6.31x10(-6) M for PE-SiT electrode. The electrodes were
      successfully applied for the potentiometric determination of pseudoephedrine
      hydrochloride (PECl) in pharmaceutical preparations with mean recovery 101.13 +/-
      0.85% and 100.77+0.79% in case of PE-PT applying batch and flow injection
      systems, respectively, and 100.75+0.85% and 100.79 +/- 0.77% in case of PE-SiT
      for batch and flow injection systems, respectively. The electrodes exhibited good
      selectivity for PECl with respect to a large number of inorganic cations, sugars
      and amino acids.

PMID- 16948432
TI  - Distribution and determination of Pb, Cd, Bi and Cu in the sea brine system:
      solution--colloidal particles--biota.
AB  - The distribution of Pb, Cd, Bi, and Cu in Black Sea brine system (solution-
      colloidal particles--biota) produced in Burgas and Pomorie salterns is studied.
      The established distribution of the title elements among the brine components is
      as follows: Pb--25% in the salt solution, 30%--in colloidal particles, 45%--in
      biota (Halobacterium salinarium and microalgae Dunaliela salina); Cu--30% in the
      salt solution, 22%--in colloidal particles, 48%--in biota. Cd and Bi are not
      detected in biota. They are uniformly distributed (50%: 50%) between the salt
      solution and colloidal particles. Two procedures for analysis are developed. The
      first one is designed for determination of the total content of the studied
      metals in brine. It involves elimination of the biota interference by addition of
      ethanol, extraction and pre-concentration of the metals with NaDDC into CCl4
      followed by FAAS determination. The second procedure intends determination of the
      elements in the separate components of the brine. It involves separation of the
      colloidal particles through centrifugation, separation of the studied elements
      from the resulting solution as dithiocarbamate complexes on a Millipore filter,
      dissolution of the retained metal species and subsequent FAAS analysis.

PMID- 16948433
TI  - Characterization of the thermal decomposition and polymerization of arprocarb
      using pyrolysis-GC-MS.
AB  - Arprocarb is a carbamate type insecticide used to control cockroaches, flies,
      mosquitoes, and is a lawn and turf insect growth regulator. In order to evaluate
      the effects of the thermal behavior of arprocarb on its bioactivity or the
      environment, its thermal decomposition and polymerization were characterized
      using pyrolysis-GC-MS (Py-GC-MS). Arprocarb was pyrolysed at 450 degrees C, 600
      degrees C, 750 degrees C, and 900 degrees C, respectively. In all 71 components
      were determined. It was found that arprocarb was obviously decomposed when the
      temperature was lower (450 approximately 750 degrees qC), and a large number of
      mono- and polycyclic aromatic hydrocarbons (PAHs) were produced at higher
      temperatures (750 approximately 900 degrees C). Furthermore, the variety of the
      representative compounds versus the temperature was reported. The research
      results can provide useful information for the understanding of the thermal
      behavior of arprocarb.

PMID- 16948435
TI  - Particulate matter, gas-phase and particle-bound polycyclic aromatic hydrocarbons
      in an urban environment heavily impacted by vehicular traffic (Bologna, Italy).
AB  - A set of 8 polycyclic aromatic hydrocarbons (PAHs) has been analysed in a traffic
      limited area in Bologna downtown, both in the gas-phase and in the particulate
      phase (PM10), and gas-to-particle partitioning has been investigated. From Sep
      2002 to May 2003, 28 high volume PM10 samplings were carried out, and in 50 % of
      the samplings, PM10 concentrations exceeded the limit of 50 microg/m3 established
      by a 1999 EU directive. A precisely defined sampling strategy was adopted to
      limit artifacts (8 h sampling in the same time interval) in the 28 samplings
      carried out in different meteorological conditions. A linear log-log correlation
      was found between gas-particle partitioning coefficients KBp and the subcooled
      liquid vapour pressures pB0LB, with rP2P = 0.82 and slope = -0.59. This empirical
      correlation may be used to anticipate the total (gas + particle-bound)
      concentration of each PAHs in this urban site, once PM10 and the particle-bound
      concentration is measured. Parallel samplings of PM10 and of PM2.5 allowed us to
      ascertain that PM2.5 represents the gross contribution to PM10 and that most of
      the particle-bound PAHs reside on the finest fraction of particulate matter.

PMID- 16948434
TI  - Studies and application of catalytic kinetic spectrophotometric determination of
      trace chromium(VI) sensitized by microemulsion medium.
AB  - A new catalytic kinetic spectrophotometric method for the determination of trace
      amount of chromium (VI) in microemulsion medium has been developed. The method is
      based on the catalytic effect of chromium (VI) on the oxidation of nuclear fast
      red in the presence of Tween-80 microemulsion and HAc-NaAc buffer solution (pH =
      5.2). The linear ranges are in the range of 0 approximately 0.0480 microg mL(-1)
      of Cr (VI) at 528 nm and the detection limit is 1.56x10(-9)g mL(-1). The method
      has been applied in determination of Cr (VI) in water and food samples with
      satisfactory results. The relative standard deviation is less than 4.6 % and the
      recovery is 93.5 approximately 104 %.

PMID- 16948436
TI  - A highly selective spectrophotometric determination of niobium (V) using 3
      hydroxy-2-[1'-phenyl-3'-(p-chlorophenyl)-4'-pyrazolyl]-4-oxo-4H-1-benzopyran as a
      complexing agent.
AB  - 3-Hydroxy-2-[1'-phenyl-3'-(p-chlorophenyl)-4'-pyrazolyl]-4-oxo-4H-1benzopyran
      (HPCPB) is used as an analytical reagent for the spectrophotometric determination
      of niobium in trace amounts with which it forms a yellow coloured complex (4:1)
      in perchloric acid medium. The complex is extractable into chloroform and shows
      absorption maximum at 407-418 nm with a molar absorptivity of 2.79 x 10(4) L mol(
      1) cm(-1) and Sandell's sensitivity equal to 0.0033 microg Nb(V) cm(-2),
      respectively. Beer's law holds good in the range 0-1.2 microg Nb ml(-1), with a
      standard deviation of +/- 0.0015 absorbance units. The method is free from the
      interference of a large number of elements and handles satisfactorily the
      analysis of various samples of varying complexity.

PMID- 16948437
TI  - Use of a glass residue in the removal of heavy metals from wastewater.
AB  - The extraction of silica from powdered glass cullet with an aqueous solution of
      sodium hydroxide has been proposed as an alternative to glass recycling aimed to
      the low temperature production of sodium silicates. The unextracted residue
      obtained after a counter current two-step extractive process at approximately 100
      degrees C and room pressure is mainly made of calcium and sodium silicate and
      shows high porosity and a large surface area. We thought that it could be active
      as an agent for the removal of heavy metals from wastewater. In this paper the
      capacity of the unextracted residue of removing six metal ions (i.e., Cu2+, Ni2+,
      Zn2+, Cd2+, Pb2+ e Cr3+) was studied in a stirred batch reactor. The data
      obtained demonstrate that the removal of metal ions from wastewater is achieved
      with high capacity in a short time and their concentration is lowered under the
      legal limits without any appreciable influence from changes of physical and
      chemical conditions. Sodium and calcium ions take the place of heavy metals in
      water while pH keeps almost neutral. The exchange mechanism was identified.

PMID- 16948438
TI  - Senio river ecosystem: characterization and distribution of inorganic species in
      water and sediments.
AB  - Analytical results are reported for the determination of inorganic species in
      water and sediments sampled in the Senio river ecosystem. The species determined
      are Cu, Pb, Cd, Zn, Co, Cr, Ni, Fe, Mn, Hg, F-, Cl-, Br, NO3-, SO4-, Na+, K+,
      Ca++, Mg++, NH4+ in integrated water, and Cu, Pb, Cd, Zn, Co, Cr, Ni, Fe, Mn, Hg
      in sediments. For all the elements, in addition to detection limits, precision
      and accuracy are given: the former, expressed as relative standard deviation
      (sr), and the latter, expressed as relative error (e), were good, being in all
      cases lower than 6%. Limitedly to Cu, Pb, Cd and Zn a critical comparison with
      voltammetric measurements is also discussed.

PMID- 16948439
TI  - Caring versus curing.

PMID- 16948440
TI  - Managing problem behaviors associated with dementia.
AB  - The older adult with dementia who exhibits problem behaviors is likely to be
      experiencing physical or psychological distress. Both can negatively affect the
      health, rehabilitation, and quality of life for the older adult. Managing problem
      behaviors can challenge the skills of the most experienced nurse. Being able to
      identify the origins of these behaviors can help caregivers respond in a way that
      will achieve behavioral management and preserve the dignity of the older adult.
      This article presents some practical measures to assist nurses with minimizing
      the negative effects of dementia-associated problem behaviors in older adults.

PMID- 16948441
TI  - Fibromyalgia syndrome: the beneficial effects of exercise.
AB  - This article highlights positive outcomes for a convenience sample of six women
      (49-64 years of age) with fibromyalgia syndrome (FMS) who participated in an
      exercise program over 5 years. This group showed improvement with various FMS
      symptoms,fitness, and psychosocial factors early in the program, then showed
      further improvement as a result of adding new exercises to the protocol during
      the fourth and fifth years. Data suggest that certain people with FMS can improve
      their functional capacity with exercise over time, and move to even higher levels
      of physical function while aging and coping with FMS. Practical advice is
      provided for rehabilitation nurses regarding exercise and FMS.

PMID- 16948442
TI  - Caregiver strain and caregiver burden of primary caregivers of stroke survivors
      with and without aphasia.
AB  - Little is known about how the burden and strain of caring for stroke patients
      with or without aphasia affects primary caregivers. This article (a) critically
      examines the literature on the burden and strain of care experienced by
      caregivers of stroke patients and (b) examines the relationship between aphasia
      and caregiver burden and strain. Two literature reviews of three databases were
      conducted. Fourteen articles (12 quantitative articles, 1 mixed-design article,
      and 1 qualitative article) were found to comply with the study criteria for the
      first literature search. A second literature search focused on the effects of
      stroke survivors' aphasia on caregiving; none of the articles retrieved met the
      inclusion criteria. This article suggests that there is a lack of research in
      this area and that several key initiatives are needed, including the development
      of an instrument with psychometric properties appropriate for assessing the
      burden and strain on caregivers of stroke patients. Implications for future
      nursing practice and research are highlighted.

PMID- 16948443
TI  - Fatigue after stroke: relationship to mobility, fitness, ambulatory activity,
      social support, and falls efficacy.
AB  - Fatigue is common and persistent in stroke survivors, yet it is not known how
      mobility deficits, fitness, or other factors, such as social support, relate to
      fatigue severity, or whether subjective fatigue contributes to reduced ambulatory
      activity. The severity of fatigue in a sample of 53 community-dwelling subjects
      with chronic hemiparetic stroke was examined, and relationships among fatigue and
      mobility deficit severity, cardiovascular-metabolic fitness, ambulatory activity,
      social support, and self-efficacy for falls were identified. Measures included
      the Fatigue Severity Scale, timed 10-meter walks, the Berg Balance Scale,
      submaximal and peak VO2, total daily step activity derived from microprocessor
      linked Step Activity Monitors, the Medical Outcomes Study Social Support Survey,
      and the Falls Efficacy Scale. Forty-six percent of the sample had severe fatigue.
      Fatigue showed no relationship to ambulatory activity. Fatigue severity was
      associated with the Berg Balance Scale (p < .01) and falls efficacy (p < .01),
      but not with cardiovascular fitness variables. Patients with elevated fatigue
      severity scores had lower social support (p < .05) and poorer falls efficacy
      scores (p < .05) than patients reporting less fatigue. Only falls efficacy was
      predictive of fatigue severity (r2 = 0.216, p < .01). Further studies are needed
      to evaluate whether rehabilitation strategies that include not only fitness and
      mobility interventions, but also social/behavioral and self-efficacy components,
      are associated with reduced fatigue and increased ambulation.

PMID- 16948444
TI  - Cough assist strategy for pulmonary toileting in ventilator-dependent spinal cord
      injured patients.
AB  - The limited innervation of muscles supporting pulmonary functioning in spinal
      cord injured (SCI) patients indicates that these individuals are at a
      particularly high risk for atelectasis and other sequelae of ventilator
      dependency. As an alternative strategy to endotracheal suctioning for secretion
      management, our acute rehabilitation facility utilizes an assistive cough device.
      This device has not been commonly utilized in the SCI population, and studies
      concerning this device have primarily focused on individuals with neuromuscular
      diseases. In our experience, utilization of mechanical in-exsufflation has
      produced positive outcomes in terms of patient satisfaction, low rates of
      ventilator-acquired pneumonia, low incidence of complications, and ease of home
      discharge with patient or family using the device long term. This article
      describes the device, as well as the protocols associated with its use in one
      ventilator spinal cord center.

PMID- 16948445
TI  - Writing with a collaborative team.
AB  - As the science of rehabilitation moves forward, the need to actively participate
      on a collaborative research team increases. Rehabilitation involves many
      different disciplines--for example, nursing, medicine, psychology, physical
      therapy, social work, and epidemiology-that affect the care of persons of all
      ages with a variety of different clinical needs. Each discipline adds a
      particular perspective to research questions, clinical situations, and eventually
      to professional publications. As such, the need for multidisciplinary
      collaborative research and publication is paramount. Nurses uniquely contribute
      their theoretical perspectives, use of varied research designs, and their close
      relationship to clinical practice to collaborative teams. Nurses bring invaluable
      expertise to the clinical research arena, especially in the areas of health
      services and implementation research, for which their on-the-ground perspective
      is invaluable to the overall goal of understanding and improving the system of
      care to enhance patient outcomes. Nurses benefit greatly by serving as active
      members on research teams because they come to know more and to be more well
      known.

PMID- 16948446
TI  - [Biochemical and immunohistochemical markers of brain injury].
AB  - Proteins released to circulation from affected tissues during primary or
      secondary trauma brain injury might be used as serum markers of glial or ganglial
      cells damage (neuron specific enolasis and S100 B protein). Other markers of
      trauma can be proved as relatively specific of diffuse axonal injury by
      immunohistochemical detectoin (amyloid prekurzor protein, neuron specific
      enolasis, glial fibrilar acidic protein and superficial antigen receptor CD 68).
      Some markers are associated with blood brain barrier damage (matrix
      metaloproteinases (MMP-2, MMP-9) and synthase of nitric oxide (iNOS)). We aimed
      in our short communication on biomechanics of developed of trauma, primary or
      secondary kinds of trauma brain injury and use of trauma brain injury markers for
      clinical diagnostics and management of patients.

PMID- 16948447
TI  - [Using of scanning electron microscopy for detection of gunshot residue].
AB  - Scanning electron microscope improves the possibility of investigation of
      surroundings near of gunshot wounds in forensic medicine, it is the next
      subsequent method for differentiating of area of entrance and exit wound,
      supplemental method for determination of firing distance, permit of detection
      (GSR) on the hand of shooter and ensured describing of samples and their stored.
      Detection of GSR provides many information about composition of bullet and
      primer. Authors are demonstrating the possibility of detection of GSR on
      experimental shooting to the krupon (pigs' skin) in different situation (such as
      in a room and in outside area) and using of different weapon (hand gun CZ No.75
      and machine gun No.58).

PMID- 16948448
TI  - A fatal case of saponated cresol ingestion.
AB  - We describe here a case of suicidal poisoning by saponated cresol ingestion. A 41
      year-old male was found unconsciousness in a park in the early morning, and an
      empty bottle of saponated cresol was found beside him. His death was confirmed
      approximately 2 hours later, despite attempts at resuscitation and intensive
      care. The autopsy revealed severe morphological damage of the upper
      gastrointestinal tract and congestion of the lung. We also observed by
      histopathological examination severe lung edema and severe erosion of the
      esophagus and stomach. Toxicological analysis also identified a high
      concentration of cresol isomer in the blood and gastric contents. The cause of
      death was given as cresol poisoning, based on the results of the autopsy and
      toxicological examination.

PMID- 16948449
TI  - Relationship between preheparin lipoprotein lipase mass concentration in serum
      and bare metal stent restenosis.
AB  - OBJECTIVES: Insulin resistance or inflammation is known to be related with
      lipoprotein lipase activity and these factors are also closely associated with
      the pathogenesis of bare-metal stent restenosis. This study examined the
      relationship between preheparin lipoprotein lipase protein (preheparin LpL mass)
      concentration in serum and bare-metal stent restenosis. METHODS: A total of 121
      lesions in 112 patients who underwent bare-metal stent implantation using NIR
      stent or S660/670 stent were examined. Subjects were divided into two groups (N
      group; patients with normal preheparin LpL mass concentration, n = 50 or L group;
      patients with low preheparin LpL mass concentration, n = 71) according to the
      mean levels of preheparin LpL mass concentration (male 39.3 ng/ml, female 50.6
      ng/ml). RESULTS: There were no differences in percutaneous coronary intervention
      or angiographical characteristics. The L group had a significantly higher
      incidence of restenosis rate and target lesion revascularization than the N group
      (N group vs L group: 8.0% vs 42.3%, p < 0.0001; 8.0% vs 33.8%, p = 0.0008,
      respectively). Homeostatic model assessment of insulin resistance as a marker of
      insulin resistance and high sensitive C-reactive protein concentration were
      significantly higher in the L group than the N group. Multiple regression
      analysis showed that only low preheparin LpL mass concentration was an
      independent factor for restenosis (t value = 3.6, p = 0.0005). CONCLUSIONS:
      Preheparin LpL mass concentration is closely associated with bare-metal stent
      restenosis and preheparin LpL mass concentration may be an important marker for
      the selection of bare-metal stent or drug-eluting stent.

PMID- 16948450
TI  - Ratio of peak early to late diastolic filling velocity of the left ventricular
      inflow is associated with left atrial appendage thrombus formation in elderly
      patients with acute ischemic stroke and sinus rhythm.
AB  - OBJECTIVES: To investigate the useful parameters of transthoracic
      echocardiography (TTE) for the diagnosis of stroke subtypes in patients with
      acute cerebral infarction. METHODS: One hundred and one acute ischemic stroke
      patients met all of the following criteria; > or = 50 years of age, normal sinus
      rhythm on admission, and transesophageal echocardiography (TEE) within 7 days
      from the onset. The clinical significance of the TTE parameters on admission was
      examined for identifying intracardiac thrombus formation as follows: left atrial
      dimension, left ventricular end-diastolic dimension, percentage fractional
      shortening, left ventricular mass index, ratio of the transmitral inflow
      velocities (E/A), and deceleration time of the E wave. RESULTS: There were 28
      patients with E/A > or = 1.0(70 +/- 12 years old) and 73 with E/A < 1.0 (73 +/-
      10 years old). No patient showed pulmonary congestion on chest radiography. There
      were no significant differences in age, TTE parameters, and plasma levels of
      brain natriuretic peptide between the two groups. Patients with E/A > or = 1.0
      had higher incidence of left atrial appendage thrombus formation and/or
      spontaneous echographic contrast than those with < 1.0 (25% vs 5%, p = 0.0058).
      There was a significant relationship between E/A and emptying flow velocity of
      the left atrial appendage (r = -0.569, p < 0.0001). Multivariate logistic
      regression analysis showed E/A was an independent predictor for left atrial
      appendage thrombus (risk ratio 1.531 per 0.1 increase, 95% confidence interval
      1.129-2.076, p = 0.0002). CONCLUSIONS: Increased level of E/A on admission was
      associated with the occurrence of left atrial appendage thrombus formation in
      patients with acute ischemic stroke.

PMID- 16948451
TI  - [Coronary artery plaque assessment using Volcano Therapeutics' Virtual Histology
      intravascular ultrasound and temperature guide wire].
AB  - OBJECTIVES: This study investigated the tissue characterization of human coronary
      artery plaque using Virtual Histology intravascular ultrasound (VH-IVUS) and
      temperature guide wire. METHODS AND RESULTS: Between August 2005 and December
      2005, VH-IVUS examination and guide wire based measurement of coronary
      temperature were performed in 66 patients: 39 with stable angina pectoris (SAP),
      and 27 with unstable angina pectoris(UAP). Patients in the acute myocardial
      infarction with necrotic tissue and thrombus were excluded. After measurement of
      distal coronary pressure and coronary temperature, the following tissue types of
      atherosclerotic plaque were evaluated by VH-IVUS: fibrotic, fibro-fatty, dense
      calcium and necrotic core. Occurrence of fibro-fatty tissue was significantly
      higher in UAP patients than in SAP patients (17.4 +/- 7.0% vs 11.2 +/- 5.2%, p =
      0.04), and coronary temperature was significantly higher in UAP patients than in
      SAP patients (0.08 +/- 0.05 vs 0.03 +/- 0.02 degrees C, p = 0.01). CONCLUSIONS:
      These results suggest that the combination of VH-IVUS analysis and measurement of
      coronary temperature may be able to predict the progression of lesions.

PMID- 16948452
TI  - Intravascular ultrasound-guided recanalization of a coronary chronic total
      occlusion located in a stent implanted subintimally: a case report.
AB  - Successful percutaneous recanalization of coronary chronic total occlusion (CTO)
      results in improved survival, as well as enhanced left ventricular function,
      reduction of angina, and improved exercise tolerance. The procedural success rate
      has increased over time, but CTO recanalization does still fail in about 20% of
      cases. Different strategies and specific devices for CTOs have been developed
      with various degrees of success. We report the case of CTO after a first
      unsuccessful treatment attempt during which subintimal wire positioning without
      reentry into the distal lumen, and stent implantation were done. At the second
      revascularization, intravascular ultrasound guidance allowed reentry of the
      distal true lumen through the stent, restoring normal flow.

PMID- 16948453
TI  - [Recurrent episodes of takotsubo-like transient left ventricular ballooning
      occurring in different regions: a case report].
AB  - A 62-year-old male with emphysema developed recurrent episodes of transient left
      ventricular ballooning occurring in different regions. Left ventriculography
      revealed symmetric mid-ventricular ballooning when he was 60 years old, and he
      also developed mid-ventricular ballooning of larger extent at the age of 62
      years. Furthermore, as he was treated for severe asthma attack 3 months later,
      left ventricular apical ballooning occurred. Echocardiography also demonstrated
      akinetic wall motion in the right ventricular apex. These episodes showed
      myocardial infarction-like onset, ST elevations on electrocardiography, no
      significant increases in cardiac enzymes, wall motion abnormalities incompatible
      with coronary artery disease, and complete recovery within a few weeks. From
      these findings, we speculate that the recurrent left ventricular wall motion
      abnormalities including the mid-ventricular ballooning were so-called takotsubo
      like left ventricular dysfunction.

PMID- 16948454
TI  - [Novel strategy of noninvasive positive pressure ventilation by intravenous
      morphine hydrochloride infusion for acute cardiogenic pulmonary edema: two case
      reports].
AB  - Standard treatment strategy for acute cardiogenic pulmonary edema includes
      noninvasive positive pressure ventilation as an alternative treatment for
      patients with acute cardiogenic pulmonary edema who require endotracheal
      intubation. Even in the improvement of hypoxemia, the beneficial effects depend
      on preload and afterload reduction with positive pressure ventilation. Although
      several strategies have been proposed for mask fitting problems, patient
      dependent ventilation mask compliance is one of the major critical problems. In
      our institution, intravenous morphine hydrochloride has been used for load
      reduction and sedative effects in such patients, achieving favorable clinical
      outcomes.

PMID- 16948455
TI  - Magnetic resonance imaging of acute myocardial infarction.

PMID- 16948456
TI  - Subarachnoid hemorrhage with left ventricular dysfunction.

PMID- 16948457
TI  - [Total hip arthroplasty after failure of per- and subtrochanteric fracture
      fixation in elderly subjects].
AB  - PURPOSE OF THE STUDY: Most pertrochanteric fractures can be successfully fixed
      with osteosynthesis. Osteosynthesis fails however is a small number of patients
      who require re-operation for implantation of a total hip prosthesis. This
      situation occurs in particular when the material has penetrated the acetabulum
      and in elderly subjects. Although this type of arthroplasty is routine practice,
      few series have been reported. We present here outcome and complications of total
      hip arthroplasty after failure of per- and sub-trochanteric fracture fixation.
      MATERIAL AND METHODS: Between 1990 and 2000, twenty patients aged 79 years on
      average (range 62-78 years) underwent revision for total hip arthroplasty after
      failure of osteosynthesis for fracture of the upper femur. A gliding THS had been
      used for fixation in 18 patients, a plate in one and a Gamma nail in one.
      Osteosynthesis failure was related to early disassembly in ten patients,
      pseudarthrosis in eight and malunion in two. Revision was performed via a
      posterolateral approach in all cases. A standard total hip prosthesis was used in
      16 patients, a longer femoral stem was required in four. Femoral components were
      cemented in 18 patients and non-cemented in two. The cup was a standard cemented
      cup in 12, retaining and cemented in eight. RESULTS: Mean operative time and
      blood loss were greater than in first-intention arthroplasties. All patients had
      lost their independence prior to the revision procedure. Despite their age, all
      recovered independence after a stay in rehabilitation. Most still required
      crutches. Use of a retaining cup enabled avoiding dislocation in all cases. For
      those who did not have a retaining cup, dislocation was the most frequent
      complication (3/12). The difficulties observed were: 1) elimination of associated
      infection before surgery; many of these elderly subjects had altered ESR and CRP
      values for various reasons; 2) abnormal position of the trochanteric mass because
      of a rotation defect; 3) malunion of the upper femur in the frontal or sagittal
      planes; 4) more or less easily achieved positioning of the femoral piece on the
      calcar; 5) difficult intraoperative identification of limb length due to loss of
      usual landmarks on the lesser and greater trochanter; 6) removal of fracture
      screws which sometimes required use of a trephine and bridging the last screw
      hole with a longer centromedullary stem. The most frequent postoperative
      orthopedic problems were leg length discrepancy (1-2 cm for eight patients),
      gluteus medius insufficiency, limping and pain at palpation of the trochanteric
      area. DISCUSSION: Despite the difficult technique and the potential complications
      which are more important than for first-intention arthroplasties, this series
      demonstrates that total hip prosthesis is a reliable solution for treating
      fixation failures of the upper femur.

PMID- 16948458
TI  - [Computer-assisted positioning of the acetabular cup for total hip arthroplasty
      based on joint kinematics without prior imaging: preliminary results with
      computed tomographic assessment].
AB  - PURPOSE OF THE STUDY: Most navigation systems for computer-assisted total hip
      arthroplasty (THA) require prior computed tomography (CT) or acquisition of
      multiple bone landmarks on the pelvis. In order to avoid these problems, we
      developed a computer-assisted navigation system without CT based on a kinematic
      approach to the hip joint. The principle is to orient the cup in relation to the
      cone describing the hip joint range of motion. The purpose of this work was to
      analyze preliminary results. MATERIAL AND METHODS: Eighteen primary THA were
      implanted with the system (16 women, two men, mean age 68 +/- 7.8 years, age
      range 54-83 years, 18 degenerative hip disease). Two optoelectronic captors were
      fixed percutaneously on the pelvis and the distal femur. The acetabulum was
      prepared first followed by the femur using reamers and broaches of increasing
      size. The last broach placed in the femur was equipped with a large head adapted
      to the newly prepared acetabulum. The range of hip motion was recorded to
      determine the maximal range of motion cone. The acetabular cup was thus
      positioned in order the prosthesis range of motion included entirely the maximal
      range of motion of the hip joint. RESULTS: One patient fell three weeks after
      implantation causing posterior dislocation; there was no recurrence. The Postel
      Merle-d'Aubligne score improved from 8 +/- 2.9 (range 3-12) preoperatively to 17
      +/- 0.8 (range 16-18) at last follow-up. None of the patients complained about
      the captor insertion and there were no cases of hematoma or fracture. Operative
      time was 35-40 minutes longer for the first four cases and was progressively
      reduced 15-20 minutes for the last four cases. Mean leg length discrepancy was
      5.6 +/- 7.5 mm (range 0-25) before implantation and 0.6 +/- 3 mm (range -5 to 10
      mm) at last follow-up. CT-scan measurements revealed a mean anteversion of the
      femoral implant of 18.2 +/- 8.5 degrees (range 0-31). Anatomic anteversion of the
      cup (measured from the pelvis landmark and thus independently of the position of
      the pelvis) was 24.7 +/- 8.8 degrees (range 12-40). The sum of the femoral and
      anatomic acetabular anteversions was 43 +/- 13.1 degrees (range 22-71).
      Anteversions were 16 degrees for the cup and 16 degrees for the stem for the one
      case of dislocation. CONCLUSION: This method can be used in routine without
      lengthening operative time significantly. It safely controls leg length and helps
      position the cup. This study demonstrated that there is no ideal position for the
      cup which can be used for all patients. Because of the wide range of inclination
      and anteversion figures, half of the cases were outside the safety zone
      recommended by Lewinnek.

PMID- 16948459
TI  - [Survival of cementless dual mobility sockets: ten-year follow-up].
AB  - PURPOSE OF THE STUDY: We report a retrospective series of 106 total hip
      prosthesis with ten years follow-up. The purpose of this study was to analyze
      survival of cementless dual mobility sockets. MATERIAL AND METHODS: The series
      included 90 consecutive patients with 106 first-intention total hip prosthesis,
      all with cementless dual mobility sockets. All prosthesis (Novae-1 socket and
      Profil-1 stem, Serf) were implanted within a 6-month period. The stainless steal
      socket was coated with alumina and had two short anchorage studs and a superior
      mooring screw and a polyethylene retentive liner. The stem had a 22.2 mm chromium
      cobalt head. The main indication for arthroplasty was degenerative joint disease.
      Mean age at implantation was 56 years (range 23-87). All patients were seen for
      physical examination and x-rays every two or three years. We noted cup survival
      at ten years (actuarial method), defining surgical revision for cup replacement
      due to an aseptic cause as the endpoint. RESULTS: Twelve patients died during the
      10-year follow-up and one was lost to follow-up. The Postel-Merle d'Aubligne
      score improved from 7.1 preoperatively to 15.8 at ten years. There were two
      isolated acetabular loosenings, two intra-prosthetic dislocations due to advanced
      wear of the polyethylene insert. The overall survival rate of the socket was
      94.6% at ten years. There were no episodes of prosthetic instability in this
      series. DISCUSSION: This study demonstrates the good ten-year survival of the
      dual mobility socket, comparable to that of conventional prostheses. The absence
      of any case of prosthetic instability in this series confirms the good short-term
      and long-term stability of the dual mobility socket. Intraprosthetic dislocation,
      due to loss of the polyethylene retaining ring is the main limitation of this
      method. The incidence was however low (2% at ten years) and treatment was not a
      problem. We recommend using the dual-mobility socket as the first-intention
      implant for patients with a high risk of post-operative instability, but also
      recommend it for all patients aged over 70 years since instability is the leading
      cause of surgical revision after this age.

PMID- 16948460
TI  - [Custom cementless stem for osteoarthritis following developmental hip
      dysplasia].
AB  - PURPOSE OF THE STUDY: Arthroplasty in developmental dysplasia of the hip joint
      raises technical problems related to the anatomy and age of the young patient.
      The purpose of this work was to report results obtained with a custom-designed
      cementless stem. MATERIAL AND METHODS: This study included 257 hips reviewed at
      mean 82 months (range 43-162 months). Mean patient age was 55 years (17-78), mean
      weight 67 kg (42-118), and mean height 164 cm (147-190). A standard imaging
      protocol was performed for all patients: AP pelvis in reclining position, AP and
      lateral views of healthy and pathological hip, AP view of entire lower limb in
      standing position, computed tomography of lower limb. La position of the greater
      trochanter and the lengthening necessary was determined from the preoperative
      films. Stem integration and migration as well as osteolysis were studied
      postoperatively. Femoral anteversion and the anteroposterior diameter of the
      paleoacetabulum were measured on the superposed computed tomographic images.
      Surgery was performed via a Watson-Jones approach to insert a noncemented cup
      hooked in the obturator foramen and implanted in the paleoacetabulum. The femur
      endomedullary cavity was prepared with a ream having the form of the definitive
      stem and the prosthetic neck was custom fit to match the desired lever arm and
      anteversion. RESULTS: The series included 174 cases of dysplasia and 83
      dislocations, 39% stage 1, 30% stage 2, 14% stage 3 and 17% stage 4. Mean
      lengthening was 39 mm. The mean helitorsion was 28 +/- 16 degrees and the mean
      anteroposterior diameter of the acetabulum was 51 mm. On average, the alpha
      correction in the prosthetic neck was -13.4 degrees (-71 degrees to +37 degrees).
      The Postel-Merle-d'Aubigne score improved from 10.4 points preoperatively to 16.7
      points at last follow-up. Postoperative x-rays showed signs of osteointegration
      in 88% of cases, osteolysis in 5% and one case of stem impaction. Ten hips (3.9%)
      required revision for replacement (7 for an aseptic problem and 3 for sepsis).
      Survival was 94.7% at 13 years. DISCUSSION: This study confirmed the anatomic
      modifications observed in patients with developmental hip dysplasia and the
      surgical problems they cause. There was no correlation between the degree of
      dislocation and the degree of helitorsion which is difficult to assess without a
      preoperative computed tomography. The survival rate at 13 years is encouraging in
      this population. The intramedullary portion of the cementless stem must be
      adapted to the dimensions of the femoral canal which decrease with increasing
      dislocation.

PMID- 16948461
TI  - [Femoral reconstruction with impacted macroporous calcium phosphate ceramic in
      revision hip arthroplasty].
AB  - PURPOSE OF THE STUDY: Management of bone stock loss remains one of the most
      challenging problems for revision hip surgery. The aim of this retrospective
      study was to report the preliminary results of peri-prosthetic femoral defect
      reconstruction with impacted granules of calcium phosphate ceramic. MATERIAL AND
      METHODS: Fourteen hips in 13 patients (3 men and 10 women) were evaluated. Age at
      surgery ranged from 30 to 79 years (mean 66.1 years). All revised devices had
      been cemented. Femoral revision was indicated for loosening in eleven hips
      (including six septic cases), femoral osteolysis (one hip), persistent pain (one
      hip), and recurrent dislocation (one hip). On the preoperative radiological
      evaluation, bone defects were assessed as SOFCOT grade II in seven case, and
      grade III in fourteen. None was rated grade IV. Once the loose prosthesis had
      been removed, bone graft or ceramic granules (14 cases) were firmly impacted in
      the femoral canal. The stem was standard and always cemented using modern
      cementing technique. RESULTS: At a mean follow-up of 34 +/- 15 months (range 14
      76 months), eleven of fourteen hips were rated good or very good according to the
      Postel-Merle-d'Aubigne score. One diaphyseal femoral fracture occurred and later
      united. Two hips required re-revision (one aseptic femoral loosening, one septic
      recurrence). Direct bonding between synthetic graft and bone was observed on
      standard radiographs in eleven cases. Stem subsidence occurred in two cases and
      was limited (mean 4.5 mm). DISCUSSION: Femoral bone reconstruction using impacted
      calcium phosphate ceramic in revision hip arthroplasty provided encouraging
      results in the short to mid term. Femoral stock restoration was achieved in the
      great majority. No adverse effect related to the use of a synthetic graft was
      noted. Further long-term evaluation is required before wider application.

PMID- 16948462
TI  - [Iliopsoas bursal distension revealing complication of total hip arthroplasty:
      five cases].
AB  - The iliopsoas bursa is situated immediately anterior to the hip joint.
      Communication can develop between a hip prosthesis and the iliopsoas bursa
      leading to distension and formation of an inguinal mass revealing complication of
      total hip arthroplasty. We report five clinical cases. The five patients with a
      total hip arthroplasty developed a mass in the Scarpa triangle which correlated
      with defective prosthesis function. We chose not to dissect the cystic mass but
      to treat the intra-articular cause. Symptoms resolved after the intervention in
      all cases. This rare condition should be envisioned if an inguinal mass develops
      or has a functional impact, particularly on the lymphovenous circulation.
      Anatomic relations can be distinguished with computed tomography. Prosthetic
      complications include infection, loosening or wear. The work-up should include
      search for infection and standard x-rays of the hip joint. Before surgery, duplex
      Doppler should be performed systematically to search for a thromboembolic
      complication.

PMID- 16948463
TI  - [Idiopathic tumoral calcinosis: two cases and review of the literature].
AB  - Two black patients from Africa presented idiopathic tumoral calcinosis. This rare
      disease, defined by the presence of calcified deposits in peri-articular tissues
      remains poorly elucidated. Pathogenesis is still hypothetical. The diagnosis can
      be established with careful physical examination and appropriate complementary
      exams, allowing early complete surgical resection without biopsy. Pathology
      examination is required for formal differential diagnosis. The present tumors
      were particularly large, but did not produce signs of compression. In the first
      patient, the tumor developed after pregnancy in the zone of antibiotic
      injections. The second patient presented multiple bilateral symmetrical
      localizations with bone invasion. Histology confirmed the nature of the lesions
      and revealed bony metaplasie in the first patient, an element rarely described.
      Prognosis is excellent with early treatment. Recurrence is the rule in the event
      of incomplete resection. We discuss the appropriate diagnostic and therapeutic
      management.

PMID- 16948464
TI  - [Ilizarov reconstruction of the distal radius after resection of a giant-cell
      tumor: a case report].
AB  - We present a case of Ilizarov reconstruction after en bloc resection of the
      distal radius. An 8-cm resection was required to remove a giant-cell tumor.
      Reconstruction was based on the ascension technique using an Ilizarov external
      fixator after corticotomy of the proximal fragment of the radius. Satisfactory
      reconstruction with formation of a neoarticulation between the radius and the
      carpus was achieved. Satisfactory wrist function was achieved and the patient was
      recurrence free at five years. The arguments leading to this therapeutic option
      are discussed.

PMID- 16948465
TI  - [Thirty years of progress in pediatric orthopedics].

PMID- 16948466
TI  - [Apropos of the article "Results at skeletal maturity after double-approach
      hemivertebrae resection"].

PMID- 16948467
TI  - Inhibitory effects of bisphosphonates on the proliferation of human ovarian
      cancer cell lines and the mechanism.
AB  - Bisphosphonates are now well established as successful agents for the prevention
      and treatment of postmenopausal osteoporosis and corticosteroid-induced bone
      loss. Bisphosphonates have also recently become important in the management of
      cancer-induced bone disease, and they now have a widely recognized role for
      patients with multiple myeloma and bone metastases secondary to breast cancer and
      prostate cancer. Recent studies suggest that, besides the strong antiosteoclastic
      activity, the efficacy of such compounds in the oncological setting could also be
      due to direct anti-tumor effect. However, the effect of bisphosphonates to
      ovarian and endometrial cancers has not been elucidated. Thus, we examined the
      direct effect of bisphosphonates on the various ovarian cancer cell lines. Except
      for etidronate, all of bisphosphonates examined had the direct inhibitory effects
      on proliferation of all ovarian cancer cell lines used. Especially, pamidronate
      had the most marked inhibitory effect and inhibited dose-dependently the
      proliferation of ovarian cancer cell lines. KFr 13 cells among ovarian cancer
      cell lines used was the most sensitive to pamidronate and the caspase 3 activity
      was markedly stimulated by treatment with pamidronate, suggesting induction of
      apoptosis.

PMID- 16948468
TI  - Cellular sensitivity to beta-diketonato complexes of ruthenium(III),
      chromium(III) and rhodium(III).
AB  - The aim of this study was to investigate cellular response to several
      ruthenium(III), chromium(III) and rhodium(III) compounds carrying bidentate beta
      diketonato ligands: [(acac)--acetylacetonate ligand, (tfac)-
      trifluoroacetylacetonate ligand]. Cell sensitivity studies were performed on
      several cell lines (A2780, cisplatin-sensitive and -resistant U2-OS and U2-OS/Pt,
      HeLa, B16) using growth-inhibition assay. Effect of intracellular GSH depletion
      on cell sensitivity to the agents was analyzed in A2780 cells. Flow cytometry was
      used to assess apoptosis by Annexin-V-FITC/PI staining, and to analyze induction
      of caspase-3 activity. Possible DNA binding/damaging affinity was investigated,
      by inductively coupled mass spectrometry, and by 14C-thymidine / 3H-uridine
      incorporation assay. Cell sensitivity studies showed that the pattern of
      sensitivity to Ru(tfac)3 complex of the two cisplatin-sensitive/-resistant
      osteosarcoma cell lines, U2-OS and U2-OS/Pt, was similar to that of A2780 cells
      (72 h exposure), with the IC50 being around 40 microM. The growth-inhibitory
      effect of Ru(acac)3 ranged over 100 microM, while Cr(III) and Rh(III) complexes
      were completely devoid of antitumor action in vitro. Ru(tfac)3 exhibited strong
      potential for apoptosis induction on A2780 cells (up to 40%) and caused cell
      cycle arrest in the S phase as well as decrease of the percent of G1 and G2
      cells. Ru(acac)3-induced apoptosis was slightly higher than 10%, whereas
      activation of caspase-3 in HeLa cells was moderate. DNA binding study revealed
      that only Cr(acac)3 was capable of binding DNA, while Cr(III) and Ru(III)
      compounds possess potential to inhibit DNA/RNA synthesis. In conclusion, only
      Ru(III) complexes showed potential for antitumor action.

PMID- 16948469
TI  - Discovery of potential sorbitol dehydrogenase inhibitors from virtual screening.
AB  - Sorbitol dehydrogenase (SDH) is the second enzyme in the polyol pathway of
      glucose metabolism and is a possible target for the treatment of the
      complications of diabetes. In this study the molecular modelling program DOCK was
      used to analyse 249,071 compounds from the National Cancer Institute Database and
      predict those with high affinity for SDH. From a total of 21 tested the 7
      compounds including flavin adenine dinucleotide disodium hydrate, (+)
      Amethopterin, 3-hydroxy-2-napthoic(2-hydroxybenzylidene) hydrazide, folic acid, N
      2,4-dinitrophenyl-L-cysteic acid, Vanillin azine and 1H-indole-2,3-dione,5-bromo
      6-nitro-1-(2,3,4-tri-O-acetyl-alpha-L-arabinopyranosyl)-(9Cl), were shown to
      inhibit SDH and displayed IC50 values of 0.192 microM, 1.1 microM, 1.2 microM,
      4.5 microM, 5.3 microM, 7 microM and 28 microM, respectively. These compounds may
      aid the design of pharmaceutical agents for the treatment of diabetes
      complications.

PMID- 16948470
TI  - Quantitative structure-activity relationship studies on matrix metalloproteinase
      inhibitors: hydroxamic acid analogs.
AB  - A quantitative structure-activity relationship study has been conducted on two
      different series of acyclic hydroxamic acid analogs acting as matrix
      metalloproteinase (MMP) inhibitors. The results suggest that in a few cases, the
      hydrophobic property of the molecules is the major governing factor. However, in
      some cases, the polarizability of the molecules is shown to be dominant. The two
      enzymes, MMP-9 and MMP-13, are shown to behave in a similar fashion with any
      group of inhibitors.

PMID- 16948471
TI  - Antioxidant and anti-inflammatory activity of aryl-acetic and hydroxamic acids as
      novel lipoxygenase inhibitors.
AB  - Lipoxygenase plays an essential role in the biosynthesis of the leukotrienes.
      Leukotrienes, as LO metabolites of arachidonic acid (AA), have been implicated as
      mediators in the pathophysiology of inflammatory diseases, host defense reactions
      and to play important role in the propagation of the diseases states,
      exacerbating the local events and ultimately leading to tissue damage. Simple
      stable molecules containing the hydroxamic acid functionality have been shown to
      inhibit 5-lipoxygenase. In fact, several hydroxamates are orally active
      inhibitors of the enzyme as determined by their ability to block the biosynthesis
      of leukotriene in vivo. In order to establish the inhibitory utility of simple
      hydroxamates several omega-phenylalkyl and omega-naphthylalkyl hydroxamic acids
      were synthesized. In an attempt to expand and delineate these results we tried to
      synthesize some more for a further pharmacochemical study. Since lipophilicity is
      a significant physicochemical property determining distribution, bioavailability,
      metabolic activity and elimination, we tried to determine experimentally their
      lipophilicity from RPTLC method. The compounds are tested in vitro on: a) soybean
      lipoxygenase inhibition, b) interaction with 1,1-diphenyl-2-picryl-hydrazyl
      (DPPH) stable free radical, c) the HO* radical mediated oxidation of DMSO, d)
      inhibition of lipid peroxidation, e) scavenging of superoxide anion radicals f)
      interaction with glutathione and g) in vivo for the inhibition of carrageenin
      induced rat paw edema. The compounds have shown important antioxidant activity,
      medium anti-inflammatory activity and potent inhibition of soybean lipoxygenase
      as a result of their physichochemical features.

PMID- 16948472
TI  - Pigment epithelium-derived factor (PEDF) blocks angiotensin II-induced T cell
      proliferation by suppressing autocrine production of interleukin-2.
AB  - Angiotensin II (Ang II) elicits numerous inflammatory-proliferative responses in
      vascular cells, thereby being involved in atherosclerosis. We have previously
      shown that pigment epithelium-derived factor (PEDF) blocks the Ang II-induced
      endothelial cell activation, thus suggesting that PEDF may play a role in
      atherosclerosis. However, effects of PEDF on T cell activation, another key steps
      of atherosclerosis, remain to be elucidated. In this study, we examined whether
      PEDF could inhibit the Ang II-induced MOLT-3 T cell proliferation in vitro and
      the way that it might achieve this effect. Ang II significantly stimulated DNA
      synthesis in MOLT-3 T cells, which was inhibited by PEDF, olmesartan, an Ang II
      type I receptor blocker, an anti-oxidant N-acetylcysteine (NAC), or antibodies
      directed against IL-2. PEDF or NAC suppressed gene expression of interleukin-2
      (IL-2) in Ang II-exposed MOLT-3 T cells. Furthermore, PEDF blocked the Ang II
      induced reactive oxygen species (ROS) generation and NADPH oxidase activity in
      MOLT-3 T cells. These results demonstrate that PEDF inhibits the Ang II-induced T
      cell proliferation by blocking autocrine production of IL-2 via suppression of
      NADPH oxidase-mediated ROS generation. Blockade by PEDF of T cell activation may
      become a novel therapeutic target for atherosclerosis.

PMID- 16948473
TI  - Heme arginate pretreatment attenuates pulmonary NF-kappaB and AP-1 activation
      induced by hemorrhagic shock via heme oxygenase-1 induction.
AB  - Hemorrhagic shock followed by resuscitation (HSR) induces oxidative stress that
      leads to acute lung injury. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in
      heme catabolism, is induced by oxidative stress and is thought to play an
      important role in the protection from oxidative tissue injuries. We previously
      demonstrated that HO-1 induction by heme arginate (HA), a strong inducer of HO-1,
      ameliorated HSR-induced lung injury and inflammation. Cellular redox state is
      known to modulate the DNA biding activity of the transcription factors; nuclear
      factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). In the present study,
      we treated rats with HA (30 mg/kg of hemin) 18 h prior to HSR and examined its
      effect on the DNA binding activity of NF-kappaB and AP-1 at 1.5 h after HSR. HSR
      significantly increased the DNA binding activity of NF-kappaB as well as AP-1,
      while HA pretreatment markedly attenuated the activities of these transcription
      factors. In contrast, administration of tin mesoporphyrin, a specific competitive
      inhibitor of HO activity, to HA-pretreated animals abolished the suppressive
      effect of HA on the activities of NF-kappaB and AP-1, and increased these
      activities to almost the same level as those in HSR animals. Our findings
      indicate that HA pretreatment can significantly suppress the increased activity
      of NF-kappaB and AP-1 induced by HSR by virtue of its ability to induce HO-1. Our
      findings also suggest that HO-1 induced by HA pretreatment ameliorates HSR
      induced lung injury at least in part mediated through the suppression of the
      activities of these transcription factors.

PMID- 16948474
TI  - Induction of quinone reductase NQO1 by resveratrol in human K562 cells involves
      the antioxidant response element ARE and is accompanied by nuclear translocation
      of transcription factor Nrf2.
AB  - The phytochemical resveratrol has been reported to induce NQO1, an enzyme
      involved in detoxification reactions, by as yet undetermined mechanisms. Using
      K562 cells as a model, we showed that 25-50 microM resveratrol increased NQO1
      that peaked at 24-48 h. A 2.5-fold rise in NQO1 protein levels was accompanied by
      a comparable elevation in mRNA copy number and a 3- to 5-fold increase in NQO1
      enzymatic activity. Fluorescent microscopic analysis in combination with
      transfection experiments with plasmids harboring different segments of the 5'
      flanking region of NQO1 gene linked to a reporter provided evidence that the
      modulation of NQO1 gene expression by resveratrol involved the antioxidant
      response element ARE, accompanied by an increase in the state of phosphorylation
      of transcription factor Nrf2 and its re-distribution to the nucleus. This change
      in cellular localization of Nrf2 may be linked to resveratrol-elicited disruption
      of the Nrf2-Keapl complex in the cytosol, followed by the translocation of Nrf2
      to the nucleus where it locates the ARE-containing 5'-promoter region of NQO1
      leading to its transcriptional activation.

PMID- 16948475
TI  - In vitro anti-mycobacterial activities of various 2'-deoxyuridine, 2'
      arabinouridine and 2'-arabinofluoro-2'-deoxyuridine analogues: synthesis and
      biological studies.
AB  - M. tuberculosis, M. bovis and M. avium infections cause the most important
      mycobacterioses leading to increased mortality in patients with AIDS. Various 5
      substituted 2'-deoxyuridines, arabinouridines, arabinocytidines and 2'
      arabinofluoro-2'-deoxyuridines were synthesized and evaluated for their in vitro
      inhibitory activity against M. bovis, M. tuberculosis and M. avium. 5-(C-1
      Substituted)-2'-deoxyuridine derivatives emerged as potent inhibitors of M. avium
      (MIC50 = 1-10 microg/mL range); 5-(1-azidovinyl)-2'-deoxyuridine being the most
      active (MIC50 = 1-5 microg/mL range). The nature of C-5 substituents appeared to
      be a determinant of anti-mycobacterial activity.

PMID- 16948476
TI  - Novel fibrinogen receptor antagonists--RGDF mimetics, 4-(1,2,3,4-tetrahydro
      isoquinoline-7-yl)amino-4-oxo-butyric acid derivatives.
AB  - Two novel RGDF mimetics were synthesized with the use of 4-(1,2,3,4-tetrahydro
      isoquinoline-7-yl)amino-4-oxo-butyric acid as a new surrogate of Arg-Gly motif.
      The synthesized compounds have demonstrated a high potency to inhibit platelet
      aggregation in vitro and to block FITC-Fg binding to alphaIIbbeta3 on washed
      human platelets.

PMID- 16948477
TI  - Insulin attenuates diabetes-related mitochondrial alterations: a comparative
      study.
AB  - This study evaluated and compared the effect of insulin treatment on the status
      of brain, heart and kidney mitochondria isolated from 12-week streptozotocin
      (STZ)-induced diabetic rats versus STZ-diabetic animals treated with insulin
      during a period of 4 weeks. Mitochondria isolated from 12-week citrate (vehicle)
      treated rats were used as control. Several mitochondrial parameters were
      evaluated: respiratory indexes (state 3 and 4 of respiration, respiratory control
      and ADP/O ratios), transmembrane potential, depolarization and repolarization
      levels, ATP, glutathione and coenzyme Q contents, production of hydrogen
      peroxide, superoxide dismutase, glutathione peroxidase and glutathione reductase
      activities and the ability of mitochondria to accumulate calcium. We observed
      that diabetes promoted a significant decrease in kidney and brain mitochondrial
      coenzyme Q9 content while this parameter was increased in heart mitochondria.
      Furthermore, diabetes induced a significant increase in hydrogen peroxide
      production in kidney mitochondria this effect being accompanied by a significant
      increase in glutathione peroxidase and reductase activities. Furthermore, brain
      mitochondria isolated from diabetic animals presented a lower ATP content and
      ability to accumulate calcium. In contrast, heart and kidney mitochondria
      presented a slight higher capacity to accumulate calcium. Insulin treatment
      normalized the levels of coenzyme Q9 and glutathione peroxidase and reductase
      activities and increased ATP content and the ability to accumulate calcium.
      Altogether these results suggest that insulin treatment attenuates diabetes
      induced mitochondrial alterations protecting against the increase in oxidative
      stress and improving oxidative phosphorylation efficiency. In this line, insulin
      therapy, besides its well-known importance in the maintenance of glycemic
      control, may help to protect against mitochondrial dysfunction associated to
      several age-related disorders such as diabetes.

PMID- 16948478
TI  - Molecular modeling studies of peptide drug candidates against SARS.
AB  - Flexible alignment and docking studies were conducted for the three octapeptides,
      ATLQANEV, AVLQSGFR, and ATLQAIAS, that were cleavable by SARS-CoV Mpro. It has
      been observed that all pharmacophores of the three peptides overlap very well,
      and that ATLQANEV binds best with the receptor, followed by AVLQSGFR, and then
      ATLQAIAS. During the process of docking the octapeptides to the SARS enzyme, the
      residues of the catalytic dyad, i.e., His-41 and Cys-145 are actively involved in
      forming the hydrogen bonds, so is the center residue (Gln) of all the three
      octapeptides. The findings are fully consistent with experimental observations.
      The present studies suggest that the octapeptides ATLQANEV and ATLQAIAS, like
      AVLQSGFR, might also be the good starting points for designing potential drugs
      against SARS.

PMID- 16948479
TI  - Development of hypoxia selective cytotoxins for cancer treatment: an update.
AB  - Increased attention has centered on exploiting hypoxia in tumors for targeting
      the design of selective antitumor agents. This review presents an update of the
      principal families of compounds under study and in clinical trials, such as N
      oxide derivatives, nitro compounds and quinone derivatives. Especially promising
      for bioreductive activation is the reduction of some moieties able to trigger a
      mechanism that releases cytotoxic antitumor drugs. The most remarkable redox
      activated triggers are presented, N-oxide, nitro, azido, quinone, metal ions, 1,2
      benzisoxazolyl and sulfoxide moieties.

PMID- 16948480
TI  - Effect of whey and soy protein supplementation combined with resistance training
      in young adults.
AB  - The purpose was to compare changes in lean tissue mass, strength, and
      myofibrillar protein catabolism resulting from combining whey protein or soy
      protein with resistance training. Twenty-seven untrained healthy subjects (18
      female, 9 male) age 18 to 35 y were randomly assigned (double blind) to
      supplement with whey protein (W; 1.2 g/kg body mass whey protein + 0.3 g/kg body
      mass sucrose power, N = 9: 6 female, 3 male), soy protein (S; 1.2 g/kg body mass
      soy protein + 0.3 g/kg body mass sucrose powder, N= 9: 6 female, 3 male) or
      placebo (P; 1.2 g/kg body mass maltodextrine + 0.3 g/kg body mass sucrose powder,
      N = 9: 6 female, 3 male) for 6 wk. Before and after training, measurements were
      taken for lean tissue mass (dual energy X-ray absorptiometry), strength (1-RM for
      bench press and hack squat), and an indicator of myofibrillar protein catabolism
      (urinary 3-methylhistidine). Results showed that protein supplementation during
      resistance training, independent of source, increased lean tissue mass and
      strength over isocaloric placebo and resistance training (P < 0.05). We conclude
      that young adults who supplement with protein during a structured resistance
      training program experience minimal beneficial effects in lean tissue mass and
      strength.

PMID- 16948481
TI  - Blood lipid responses after continuous and accumulated aerobic exercise.
AB  - The purpose of this study was to compare blood lipid responses to continuous
      versus accumulated exercise. Nine participants completed the following conditions
      on separate occasions by treadmill walking/jogging at 70% of VO2max: 1) one 500
      kcal session and 2) three 167 kcal sessions. Total cholesterol (TC), high-density
      lipoprotein cholesterol (HDL-C), and triglycerides (TG) concentrations were
      measured from serum samples obtained 24 h prior to and 24 and 48 h after
      exercise. All blood lipid responses were analyzed in 2 (condition) x 3 (time)
      repeated measures ANOVAs. HDL-C increased by 7 mg/dL over baseline at 48 h post
      exercise with three accumulated sessions versus 2 mg/dL with continuous exercise
      (P < 0.05). Triglyceride concentrations were unchanged in both conditions. These
      findings suggest that three smaller bouts accumulated on the same day may have a
      modestly greater effect for achieving transient increases in HDL-C compared to a
      continuous bout of similar caloric expenditure.

PMID- 16948482
TI  - Protective effect of physical activity independent of obesity on metabolic risk
      factors.
AB  - The purpose of this prospective study was to examine the effect of physical
      activity independent of obesity on metabolic risk factors. A total of 358
      participants were recruited from the Department of Health Management of Chang
      Gung Medical Center. Physical activity was assessed using a 3-d activity record.
      Body-mass index (BMI) and metabolic risk factors were also assessed. Our findings
      demonstrate that an effect of obesity that was statistically independent of the
      levels of physical activity is associated with metabolic risk factors. Moreover,
      physical activity displayed inverse associations with triglycerides, and fasting
      plasma glucose and a positive association with HDL cholesterol. Those
      participants with time spent in moderate activity more than 0.5 h each day had
      significantly less risk of high fasting glucose. Significantly, these
      associations were independent of BMI.

PMID- 16948483
TI  - Effect of high dose vitamin C supplementation on muscle soreness, damage,
      function, and oxidative stress to eccentric exercise.
AB  - This study investigated if vitamin C supplementation before and after eccentric
      exercise could reduce muscle soreness (MS), oxidative stress, and muscle
      function. Eighteen healthy men randomly assigned to either a placebo (P) or
      vitamin C (VC) (3 g/d) treatment group took pills for 2 wk prior and 4 d after
      performing 70 eccentric elbow extensions with their non-dominant arm. MS
      increased in both groups with significantly reduced MS for the first 24 h with
      VC. Range of motion was reduced equally in both groups after the exercise (P > or
      = 0.05). Muscle force declined equally and was unaffected by treatment. VC
      attenuated the creatine kinase (CK) increase at 48 h after exercise with similar
      CK after this time. Glutathione ratio (oxidized glutathione/total glutathione)
      was significantly increased at 4 and 24 h with P but VC prevented this change.
      These data suggest that vitamin C pretreatment can reduce MS, delay CK increase,
      and prevent blood glutathione oxidation with little influence on muscle function
      loss.

PMID- 16948484
TI  - Body composition, dietary intake, and iron status of female collegiate swimmers
      and divers.
AB  - This study determined the effect of training on body composition, dietary intake,
      and iron status of eumenorrheic female collegiate swimmers (n = 18) and divers (n
      = 6) preseason and after 16 wk of training. Athletes trained on dryland
      (resistance, strength, flexibility) 3 d/wk, 1.5 h/d and in-water 6 d/wk, nine, 2
      h sessions per week (6400 to 10,000 kJ/d). Body-mass index (kg/m2; P = 0.05),
      waist and hip circumferences (P < or = 0.0001), whole body fat mass (P = 0.0002),
      and percentage body fat (P < or = 0.0001) decreased, whereas lean mass increased
      (P = 0.028). Using dual-energy X-ray absorptiometry, we found no change in
      regional lean mass, but fat decreased at the waist (P = 0.0002), hip (P =
      0.0002), and thigh (P = 0.002). Energy intake (10,061 +/- 3617 kJ/d) did not
      change, but dietary quality improved with training, as reflected by increased
      intakes of fiber (P = 0.036), iron (P = 0.015), vitamin C (P = 0.029), vitamin B
      6 (P = 0.032), and fruit (P = 0.003). Iron status improved as reflected by slight
      increases in hemoglobin (P = 0.046) and hematocrit (P = 0.014) and decreases in
      serum transferrin receptor (P < or = 0.0001). Studies are needed to further
      evaluate body composition and iron status in relation to dietary intake in female
      swimmers.

PMID- 16948485
TI  - The determination of subcutaneous body fat percentage by measuring skinfold
      thickness in teenagers in Turkey.
AB  - Our aim in this study was to determine the body fat percentage of teenagers in
      Diyarbakir, a city in southeast Turkey. The study included 1118 children between
      the ages of 10 to 15. Basic anthropometric measurements including body-mass index
      (BMI) and skinfold thickness were taken. The skinfold thickness were measured
      with a Lange skinfold caliper. Fat mass percentage (FM %) was predicted by using
      skinfold thickness equations. Differences between boys and girls across age
      groups for weight, height, and BMI were found to be statistically significant (P
      < 0.0001). With respect to skinfold thickness in the 10-y-old group, the
      thickness at triceps and subscapular sites in girls was higher than those of
      boys. In the 12-y-old group, the thickness was found to be higher in girls than
      boys at the triceps, biceps, and subscapular sites. We found that an increase in
      skinfold thickness in the 13, 14, and 15-y-old groups was significantly higher
      among girls than boys and tended to increase with age. However, such a tendency
      was not shown in boys. This tendency was found only at the triceps site in 10,
      12, and 13-y-old boys. In addition, the skinfold thickness at the biceps site was
      found to be greater in the 14-y-old boys. The body fat mass percent in girls,
      especially those older than age 13, was also increased.

PMID- 16948486
TI  - Does Rhodiola rosea possess ergogenic properties?
AB  - Rhodiola rosea is an herb purported to possess adaptogenic and ergogenic
      properties and has recently been the subject of increased interest The purpose of
      this article was to review and summarize recent investigations of the potential
      performance-enhancing properties of Rhodiola rosea. Such studies have generated
      equivocal results. Several investigations conducted in Eastern Europe have
      indicated that Rhodiola rosea ingestion may produce such positive effects as
      improved cognitive function and reduced mental fatigue. Other research from this
      region has illustrated enhanced endurance exercise performance in both humans and
      rats. Studies conducted in Western Europe and in North America have indicated
      that Rhodiola rosea may possess substantial antioxidant properties but have
      produced mixed results when attempting to demonstrate an ergogenic effect during
      exercise in humans.

PMID- 16948487
TI  - Serum basal hormone concentrations and muscle mass in aging women: effects of
      strength training and diet.
AB  - This study examined the effects of strength training and diet on serum basal
      hormone concentrations and muscle mass in aging women. Fifty-one women age 49 to
      74 y were divided into two groups: strength training and nutritional counseling
      (n = 25), and strength training (n = 26). Both groups performed strength training
      twice a week for 21 wk. Nutritional counseling was given to attain sufficient
      energy and protein intake and recommended intake of fat and fiber. We found that
      the cross-sectional area of the quadriceps femoris increased by 9.5 +/- 4.1% in
      the nutritional counseling group versus 6.8 +/- 3.5% in the strength training
      only group after training (P < 0.052). Nutritional counseling evoked dietary
      changes such as increases in the proportion of energy from protein and the ratio
      of polyunsaturated and saturated fatty acids. Strength training increased
      testosterone and testosterone/sex hormone-binding globulin ratio after the first
      half of training, but these returned to baseline values at the end of the entire
      training period. Changes in serum basal hormone concentrations did not differ
      between the groups. Our results support the conclusion that nutritional
      counseling can contribute to the increase in the muscle cross-sectional area
      during prolonged strength training in aging women.

PMID- 16948489
TI  - Fast-scanning atomic force microscopy reveals the molecular mechanism of DNA
      cleavage by ApaI endonuclease.
AB  - Newly developed fast-scanning atomic force microscopy (AFM) allows the dissection
      of molecular events such as DNA-enzyme reactions at the single-molecule level.
      With this novel technology, a model is proposed of the DNA cleavage reaction by a
      type IIP restriction endonuclease ApaI. Detailed analyses revealed that ApaI
      bound to DNA as a dimer and slid along DNA in a one-dimensional diffusion manner.
      When it encountered a specific DNA sequence, the enzyme halted for a moment to
      digest the DNA. Immediately after digestion, the ApaI dimer separated into two
      monomers, each of which remained on the DNA end and then dissociated from the DNA
      end. Thus, fast-scanning AFM is a powerful tool to aid the understanding of
      protein structures and dynamics in biological reactions at the single-molecule
      level in sub-seconds.

PMID- 16948490
TI  - Paramagnetic capture mode magnetophoretic microseparator for blood cells.
AB  - The paper presents the characterisation of a continuous paramagnetic capture
      (PMC) mode magnetophoretic microseparator for separating red and white blood
      cells from whole blood based on their native magnetic properties. The PMC
      microseparator separates the blood cells using a high-gradient magnetic
      separation method without the use of additives such as magnetic tagging. The
      microseparator is fabricated using microfabrication technology, enabling the
      integration of micro-scale magnetic flux concentrators in an aqueous micro
      environment. Experimental results show that the PMC microseparator can
      continuously separate out 91.1% of red blood cells from whole blood within 5 min,
      using an external magnetic flux of 0.2 T from a permanent magnet. Monitoring of
      white blood cells dyed with a fluorescent probe shows that 87.7% of white blood
      cells are separated out by the 0.2 T external magnetic flux applied to the PMC
      microseparator.

PMID- 16948491
TI  - Integration of microfluidics with biomedical infrared spectroscopy for analytical
      and diagnostic metabolic profiling.
AB  - We describe how infrared spectroscopy of dry films (IRDF) can provide diagnostic
      information, and how we expect integration with laminar fluid diffusion interface
      (LFDI) sample pre-processing to generate new analytical and diagnostic tests.
      LFDI pre-processing provides sample clean-up and analyte separation. The
      sensitivity of IRDF to certain analytes is enhanced through the depletion of
      sample constituents that otherwise obscure relevant spectral features, permitting
      the deposition of films with larger sample volumes and, hence, of greater
      effective optical pathlength for the targeted analytes. An integrated LFDI-IRDF
      technology holds promise both as a method for rapid point-of-care quantitative
      analysis of biological fluids and as the engine of discovery for a wide range of
      novel diagnostic methods based upon metabolic profiling. In particular,
      successful integration will provide a versatile and cost effective technology
      platform that will allow for the accurate quantification of low-concentration
      analytes that are otherwise inaccessible and will provide the basis for
      diagnostic and prognostic methods that would otherwise be impossible. The
      specific question addressed by the proof-of-concept study summarised here is
      whether the spectra of LFDI processed samples can provide analytical methods that
      are more accurate than otherwise possible without LFDI pre-processing. The
      enrichment of serum creatinine is accomplished, with subsequent enhancement of
      its spectral contribution permitting quantification of this clinically important
      analyte beyond that achievable with no pre-processing. Finally, to illustrate the
      potential in diagnostic applications, two recently initiated studies are
      outlined, one involving chronic kidney disease and the other for chronic and
      acute coronary artery disease.

PMID- 16948492
TI  - Engineering challenges of BioNEMS: the integration of microfluidics, micro- and
      nanodevices, models and external control for systems biology.
AB  - Systems biology, i.e. quantitative, postgenomic, postproteomic, dynamic,
      multiscale physiology, addresses in an integrative, quantitative manner the
      shockwave of genetic and proteomic information using computer models that may
      eventually have 10(6) dynamic variables with non-linear interactions.
      Historically, single biological measurements are made over minutes, suggesting
      the challenge of specifying 10(6) model parameters. Except for fluorescence and
      micro-electrode recordings, most cellular measurements have inadequate bandwidth
      to discern the time course of critical intracellular biochemical events. Micro
      array expression profiles of thousands of genes cannot determine quantitative
      dynamic cellular signalling and metabolic variables. Major gaps must be bridged
      between the computational vision and experimental reality. The analysis of
      cellular signalling dynamics and control requires, first, micro- and nano
      instruments that measure simultaneously multiple extracellular and intracellular
      variables with sufficient bandwidth; secondly, the ability to open existing
      internal control and signalling loops; thirdly, external BioMEMS micro-actuators
      that provide high bandwidth feedback and externally addressable intracellular
      nano-actuators; and, fourthly, real-time, closed-loop, single-cell control
      algorithms. The unravelling of the nested and coupled nature of cellular control
      loops requires simultaneous recording of multiple single-cell signatures.
      Externally controlled nano-actuators, needed to effect changes in the
      biochemical, mechanical and electrical environment both outside and inside the
      cell, will provide a major impetus for nanoscience.

PMID- 16948493
TI  - Microfluidic sensor for dynamic surface tension measurement.
AB  - A novel microfluidic sensor for measuring dynamic gas-liquid interfacial tension
      is reported. The device consists of a microfluidic chip with a microchannel
      network and an optical detection system. The sample is introduced into a main
      channel, while air is injected through a T-junction. Owing to the fixed flow rate
      ratio used for the sensor, surface tension is the only parameter determining
      bubble formation frequency, which can be measured by optical detection. Although
      the bubble is represented by a pulse in the output signal, the formation
      frequency is simply the frequency of the output signal. Measurements were carried
      out for aqueous solutions with different concentrations of the ionic surfactant
      cetyl trimethyl ammonium bromide. Surface tensions of these solutions were
      calibrated with a commercial tensiometer. The measurement results show a clear
      relationship between surface tension and formation frequency. The sensor can be
      used to identify the critical micelle concentration of the surfactant. The sensor
      potentially allows the use of a minute amount of sample compared with the
      relatively large amount required for existing commercial systems.

PMID- 16948494
TI  - Membrane channels as a tool to control nanoreactors.
AB  - We present an example of the use of self-assembly of biomolecules to create
      nanostructured building blocks. The resulting individual compartments can be
      tailored to fulfil specific functions: catalysis of a chemical reaction in a
      confined environment, detection on a molecular level and feedback with the
      outside. For example, such individually designed components can be assembled to
      build up macroscopic chemically active filters. The main component is membrane
      channels acting as molecular sieves, able to control the permeation across the
      capsule wall. We introduce briefly a new microdevice to characterise membrane
      channels with a future potential for high-throughput screening of channel
      properties based on automation, parallelisation and the use of microfluidics.
      Subsequently, we outline a possible application for channel-forming proteins:
      encapsulation of charged polymers or proteins into liposomes and restriction of
      diffusion through transmembrane channels to small ions, creating a Donnan
      potential. This Donnan potential can be used for external manipulation of
      nanocontainers by coupling of the capsule to an external electric field, or for
      the selective uptake of small charged molecules into the capsule.

PMID- 16948495
TI  - Freestanding polyelectrolyte multilayers as functional and construction elements.
AB  - This article reviews the progress in the field of polyelectrolyte multilayer
      membranes with special attention to freestanding membranes. These can be prepared
      both in the form of hollow capsules and as flat membrane sheets. While (bio)
      functionality, or bioactivity as it is known, from solid supported multilayers is
      maintained, additional applications arise for the freestanding membranes in the
      fields of encapsulation, separation and micromechanics. The production processes
      and functionalities achieved for capsules and flat sheets. The integration of
      membranes into larger scale structures is essential for their use and an overview
      of existing strategies is given. In particular, the way in which arrays of micro
      compartments can be built up is shown, and their potential for sensing and
      combinatorial chemistry discussed. Recent results on the applications of such
      systems as membrane sensors in the case of flat membrane sheets are also
      discussed.

PMID- 16948496
TI  - Characterisation of pore structures in nanoporous materials for advanced
      bionanotechnology.
AB  - Porous materials are potential candidates for applications in various fields,
      such as bionanotechnology, gas separation, catalysts and micro-electronics. In
      particular, their applications in bionanotechnology include biosensors,
      biomedical implants and microdevices, biosupporters, bio-encapsules, biomolecule
      separations and biomedical therapy. All these bionanotechnology applications
      utilise the shape, size and size distribution of pores in porous materials.
      Therefore the controlled creation of pores with desired shape, size and size
      distribution is most important in the development of nanoporous materials.
      Accordingly, the accurate evaluation of pore structure is necessary in the
      development of nanoporous materials and their applications. This article reviews
      recent developments in analytical techniques to characterise the pore structures
      of nanoporous materials.

PMID- 16948498
TI  - Quantitation of estrogen receptors and relaxin binding in human anterior cruciate
      ligament fibroblasts.
AB  - The significantly higher incidence of anterior cruciate ligament (ACL) injuries
      in collegiate women compared with men may result from relative ligament laxity.
      Differences in estrogen and relaxin activity, similar to that seen in pregnancy,
      may account for this. We quantified estrogen receptors by flow cytometry and
      relaxin receptors by radioligand binding assay in human ACL cells and compared
      the presence of these receptors in males and females. ACL stumps were harvested
      from seven males and eight females with acute ACL injuries. The tissue was placed
      in M199 cell culture medium. Outgrowth cultures were obtained, and passage 2
      cells were used for all studies. Estrogen receptor determination was performed
      using flow cytometry. Relaxin binding was performed in ACL cells derived from
      five female and male patients using I(125)-labeled relaxin. Estrogen receptors
      were identified by flow cytometry in 4 to 10% of ACL cells. Mean fluorescence of
      cells expressing estrogen receptors was approximately twice that of controls,
      with no significant differences between males and females. Relaxin studies showed
      low-level binding of I(125)-relaxin-labeled ACL cells. Relaxin binding was
      present in four out of five female ACL cells versus one out of five male ACL
      cells.

PMID- 16948497
TI  - Characterization of TGF-beta1 type II receptor expression in cultured cortical
      astrocytes.
AB  - The transforming growth factor-betas (TGF-betas) comprise a family of pleiotropic
      members that signal through two types of serine/threonine kinase receptors, named
      TGFRI (TGF-beta type I receptor) and TGFRII (TGF-beta type II receptor). We
      previously demonstrated that cortical neurons increase the astrocyte maturation
      marker, glial fibrillary acidic protein (GFAP), and thus, astrocyte
      differentiation, by inducing TGF-beta1 secretion by astrocytes in vitro. Although
      TGF-beta receptor expression has been described in different brain regions and
      cell types, their localization is still a subject of discussion. In the present
      work, we analyzed TGFRII expression in cultured cortical astrocytes from
      embryonic and newborn animals by immunocytochemistry, Western blot, and reverse
      transcriptase-polymerase chain reaction (RT-PCR). We report for the first time
      expression of TGFRII in embryonic glia. TGFRII immunostaining was punctual and
      spread throughout the cellular membrane of embryonic and newborn astrocytes.
      Western blot and RT-PCR assays revealed similar levels of the receptor in
      astrocytes from different ages. Identification of TGFRII in embryonic astrocytes
      is novel and might point to the multipotent precursor cell, radial glia, as a
      potential target for TGFbeta1 during astrocyte development.

PMID- 16948499
TI  - Cloning and characterization of osteoclast precursors from the RAW264.7 cell
      line.
AB  - Osteoclasts are bone-resorbing cells that differentiate from macrophage
      precursors in response to receptor activator of NF-kappaB ligand (RANKL). In
      vitro models of osteoclast differentiation are principally based on primary cell
      cultures, which are poorly suited to molecular and transgene studies because of
      the limitations associated with the use of primary macrophage. RAW264.7 is a
      transfectable macrophage cell line with the capacity to form osteoclast-like
      cells. In the present study, we have identified osteoclast precursors among
      clones of RAW264.7 cells. RAW264.7 cell were cloned by limiting dilution and
      induced to osteoclast differentiation by treatment with recombinant RANKL.
      Individual RAW264.7 cell clones formed tartrate resistant acid phosphatase (TRAP)
      positive multinuclear cells to various degrees with RANKL treatment. All clones
      tested expressed the RANKL receptor RANK. Each of the clones expressed the
      osteoclast marker genes TRAP and cathepsin-K mRNA with RANKL treatment. However,
      we noted that only select clones were able to form large, well-spread, TRAP
      positive multinuclear cells. Clones capable of forming large TRAP-positive
      multinuclear cells also expressed beta3 integrin and calcitonin receptor mRNAs
      and were capable of resorbing a mineralized matrix. All clones tested activated
      NF-kappaB with RANKL treatment. cDNA expression profiling of osteoclast precursor
      RAW264.7 cell clones demonstrates appropriate expression of a large number of
      genes before and after osteoclastic differentiation. These osteoclast precursor
      RAW264.7 cell clones provide a valuable model for dissecting the cellular and
      molecular regulation of osteoclast differentiation and activation.

PMID- 16948501
TI  - Mitochondrial biochemical activities and heteroplasmy evolution in established D.
      subobscura cell line.
AB  - A mutant strain of drosophila (D. subobscura) has two types of mitochondrial
      genomes: a small population (20%) identical to that of the wild strain (15.9 kb)
      and a predominant population (80%) which has undergone a 5-kb deletion affecting
      more than 30% of the coding zone. Two cell lines were established from
      homogenates of embryos from mutant and wild strains. The activities of the
      respiratory complexes measured in the different cell lines are much lower than in
      the flies, indicating a glycolytic metabolism. Various modifications of the
      medium composition did not change this metabolic pathway. The mutant cell line
      has two types of populations of mitochondrial genomes and the heteroplasmy is
      equivalent to that measured in the mutant strain. However, the biochemical
      characteristics differ from those observed in the flies (i.e., the decrease of
      complex I and III activities), and the various systems of compensation for the
      consequences of the deletion that are showed in the mutant strain are no longer
      observed. Furthermore, in contrast with observations made on mutant flies, the
      heteroplasmy appears unstable in the mutant cell lines: after 60 or so
      generations, it progressively decreases until it disappears completely. The
      limited importance of mitochondrial energy metabolism in cells may explain the
      low impact of the mutation on the established cell line, in contrast to what is
      seen in the mutant strain.

PMID- 16948500
TI  - Strategy for the development of a matched set of transport-competent, angiotensin
      receptor-deficient proximal tubule cell lines.
AB  - In the proximal convoluted tubule (PCT) angiotensin II (Ang II) modulates fluid
      and electrolyte transport through at least two pharmacologically distinct
      receptor subtypes: AT(1) and AT(2). Development of cell lines that lack these
      receptors are potentially useful models to probe the complex cellular details of
      Ang II regulation. To this end, angiotensin receptor- deficient mice were bred
      with an Immortomouse(R), which harbors a thermolabile SV40 large-T antigen (Tag).
      S1 PCT segments from kidneys of F(2) mice were microdissected, placed in culture,
      and maintained under conditions that enhanced cell growth, i.e., promoted Tag
      expression and thermostability. Three different types of angiotensin receptor
      deficient cell lines, (AT(1A) [-/-], Tag [+/-]), (AT(1B) [-/-], Tag [+/-]), and
      (AT(1A) [-/-], AT(1B) [-/-], Tag [+/+]), as well as wild type cell lines were
      generated. Screening and characterization, which were conducted under culture
      conditions that promoted cellular differentiation, included: measurements of
      transepithelial transport, such as basal monolayer short-circuit current (Isc; -3
      to 3 microA/cm2), basal monolayer conductance (G, 2 to 10 mS/cm2), Na3(+)
      phosphate cotransport (DeltaIsc of 2 to 3 microA/cm(2) at 1 mM), and Na(3)(+)
      succinate cotransport (DeltaIsc of 1 to 9 microA/cm(2) at 2 mM). Morphology of
      cell monolayers showed an extensive brush border, well-defined tight junctions,
      and primary cilia. Receptor functionality was assessed by Ang II-stimulated beta
      arrestin 2 translocation and showed an Ang II-mediated response in wild type but
      not (AT(1A) [-/ -], AT(1B) [-/-]) cells. Cell lines were amplified, yielding a
      virtually unlimited supply of highly differentiated, transport-competent,
      angiotensin receptor-deficient PCT cell lines.

PMID- 16948502
TI  - Heterogeneity amongst splenic stromal cell lines which support dendritic cell
      hematopoiesis.
AB  - Long-term cultures (LTC) producing dendritic cells (DC) have been previously
      established from spleen. LTC support the development of nonadherent cells
      comprising small DC progenitors and immature DC. Similarly, the splenic stroma
      STX3, derived from a LTC which ceased DC production, can support DC development
      from precursors in overlaid bone marrow. The STX3 stroma is an immortalised mixed
      population of endothelial cells and elongated spindle-shaped cells, thought to be
      fibroblasts. The stromal cell components of STX3 have been studied here. A panel
      of 102 cell lines was established by single-cell sorting. A range of clone
      morphology, including cobblestone cells and elongated spindle-shaped cells, was
      reflective of heterogeneity in STX3. However, similar expression levels for the
      endothelial genes ACVRL1/ ALK1, COL18A1, and MCAM in 13 splenic stromal cell
      lines suggested that both cell types had endothelial origin. The hematopoietic
      support function of stromal clones was tested in coculture assays with a bone
      marrow cell overlay. Splenic stromal cell lines with different morphology were
      both supporters and nonsupporters of hematopoiesis, in terms of foci formation or
      release of suspension cells. Cloning of STX3 led to the isolation of a panel of
      splenic endothelial cell lines heterogeneous in terms of morphology and
      hematopoietic support function.

PMID- 16948503
TI  - Human diploid fibroblast cells in senescence; cycling through polyploidy to
      mitotic cells.
AB  - Previously, it was found that senescent cells can undergo a modified cell cycle
      with mitotic cells as the end results. The major cycling events started with
      polyploidization, followed by depolyploidization to multinucleated cells (MNCs).
      These latter cells produced mononuclear offspring cells that could express
      mitotic cell divisions. In this report the emphasis is on late senescent
      fibroblasts that exhibited the senescence-associated change in cell morphology to
      large flat cells. Prior to live cell photography, flat cell cultures were
      maintained for months in the same culture flasks and therefore judged to be in a
      late senescent phase. All of the cellular events outlined above were present in
      these old cell cultures. Time lapse pictures showed movements of mitotic daughter
      cells away from each other and alignment of the chromosomes on the metaphase
      plate was visible in other mitotic cells. These data challenge the common view
      that cell senescence is irreversible and, therefore, an antitumor mechanism. A
      new finding was that the spike in polyploid cells in the near senescent phase
      consisted of cells with pairs of sister chromosomes from endoreduplication of DNA
      (two rounds of DNA synthesis and no mitosis). The lack of cells with 92 single
      chromosomes (e.g., G2 tetraploid cells) suggested that these polyploid cells also
      went through a changed cell cycle. The question now is whether these atypical
      polyploid cells are a subpopulation in senescence that can undergo the cycling
      from polyploidy to genome-reduced mitotic cells.

PMID- 16948505
TI  - Frozen section of thyroid and parathyroid specimens.

PMID- 16948504
TI  - Effects of Ulmus davidiana planch on mineralization, bone morphogenetic protein
      2, alkaline phosphatase, type I collagen, and collagenase-1 in bone cells.
AB  - Ulmus davidiana Planch (Ulmaceae) (UD) long has been known to have anti
      inflammatory and protective effects on damaged tissue, inflammation, and bone
      among other functions. The herbal medicine also is being used in Oriental
      medicine to treat osteoporosis. In a preliminary study, treatment of osteoclasts
      containing long bone cells with the water extract of UD bark prevented the
      intracellular maturation of cathepsin K (cat K), and thus, it was considered that
      UD is a pro-drug of a potent bone-resorption inhibitor. To further clarify the
      role of UD in ossification, we investigated the effects of UD on the
      proliferation and differentiation of osteoblastic cell lines in vitro. In this
      study, we assessed the effects of UD on osteoblastic differentiation in
      nontransformed osteoblastic cells (MC3T3-E1) and rat bone marrow cells. UD
      enhanced alkaline phosphatase (ALP) activity and mineralization in a dose- and
      time-dependent fashion. This stimulatory effect of the UD was observed at
      relatively low doses (significant at 5-50 microg/ml and maximal at 50 microg/ml).
      Northern blot analysis showed that UD (100 microg/ml) increases in bone
      morphogenic protein-2 as well as ALP mRNA concentrations in MC3T3-E1 cells. UD
      slightly increased in type I collagen mRNA abundance throughout the culture
      period, whereas it markedly inhibited the gene expression of collagenase-1
      between days 15 and 20 of culture. These results indicate that UD has anabolic
      effects on bone through the promotion of osteoblastic differentiation, suggesting
      that it could be used for the treatment of common metabolic bone diseases such as
      osteoporosis.

PMID- 16948506
TI  - The skilled phlebotomist.

PMID- 16948507
TI  - Improvements in clinical diagnostic accuracy after a 5-year systematic analysis
      of clinical and autopsy discrepancies.

PMID- 16948508
TI  - Assessing performance, productivity, and staffing needs in pathology groups:
      observations from the College of American Pathologists PathFocus pathology
      practice activity and staffing program.
AB  - CONTEXT: The PathFocus program affords the opportunity for participating
      pathology practices to be compared with other practices that have similar
      characteristics. OBJECTIVES: To demonstrate variability in workload among
      different pathology practice settings and to determine practice characteristics
      that influence staffing levels. DESIGN: Among 228 group practices in the
      PathFocus database, group practice settings were analyzed. The practice
      characteristics that were highly correlated with staffing levels are presented.
      RESULTS: Activities that showed significant variation include surgical pathology
      (P = .003), cytopathology (P = .006), miscellaneous (P = .006), and professional
      development (P = .003). Group practices report up to 4% of hours devoted to
      clinical pathology consultation, on average, and from 20% to 25% to
      administration and management. There are strong positive associations with
      staffing levels for lower-complexity Current Procedural Terminology code volumes
      (P < .001) and higher-complexity Current Procedural Terminology code volumes (P =
      .006). CONCLUSION: The settings of pathology practices carry specific commitments
      of time that are different and not equally distributed among all practice
      settings and strongly influence staffing requirements.

PMID- 16948511
TI  - Medical examiners, coroners, and public health: a review and update.
AB  - CONTEXT: Traditionally, the emphasis of work done by medical examiners, coroners,
      and the death investigation community has been viewed as serving the criminal
      justice system. During the last several decades, however, an important role for
      these 3 groups has emerged within public health. OBJECTIVE: To provide important
      background information on death investigation systems, the evolution and
      framework of public health entities that rely on information gathered by medical
      examiners and coroners, and the role of medical examiners and coroners in
      epidemiologic research, surveillance, and existing public health programs and
      activities. DATA SOURCES: Previous articles on epidemiologic aspects of forensic
      pathology and the role of medical examiners and coroners in epidemiologic
      research and surveillance; a review of the Web sites of public health and safety
      agencies, organizations, and programs that rely on medical examiner and coroner
      data collected during medicolegal investigations; and a review of recent public
      health reports and other publications of relevance to medical examiner and
      coroner activities. CONCLUSIONS: The role of medical examiners and coroners has
      evolved from a criminal justice service focus to a broader involvement that now
      significantly benefits the public safety, medical, and public health communities.
      It is foreseeable that the public health role of medical examiners and coroners
      may continue to grow and that, perhaps in the not-too-distant future, public
      health impact will surpass criminal justice as the major focus of medicolegal
      death investigation in the United States.

PMID- 16948509
TI  - The significance of certification in liquid-based cytology and performance in the
      college of american pathologists interlaboratory comparison program in
      cervicovaginal cytopathology.
AB  - CONTEXT: Morphology training and certification provided by the manufacturer is
      required before laboratories are allowed to prepare and interpret liquid-based
      cytology (LBC) gynecologic slides. Whether this certification is associated with
      improved LBC interpretation performance is not known. OBJECTIVE: To determine
      whether LBC certification correlates with performance. DESIGN: The results of the
      College of American Pathologists Interlaboratory Comparison Program in
      Cervicovaginal Cytopathology for the year 2004 were reviewed. During this year a
      question on the answer form asked participants whether they were certified in LBC
      preparations. Participant responses were analyzed at 2 levels of agreement with
      the reference diagnosis of unknown glass slides mailed quarterly. RESULTS: For
      cytotechnologists and pathologists, participants who were LBC certified had a
      significantly lower total discordant rate to series than participants who were
      not certified for validated LBC ThinPrep (Cytyc Corp, Marlborough, Mass)
      preparations (P < .001 for both groups). The results were similar for validated
      conventional preparations for pathologists but not for cytotechnologists. The
      differences were present across most individual diagnostic series. Differences
      were most striking for low-grade squamous intraepithelial lesions. In addition,
      cytotechnologists and pathologists who were certified had a significantly lower
      total discordant rate to the exact diagnosis for validated LBC ThinPrep slides
      than those who were not certified (discordant rates for cytotechnologists, 14.14%
      and 23.36%, respectively, P < .001; for pathologists, 15.99% and 24.07%,
      respectively, P < .001). CONCLUSION: Although not all confounding factors were
      excluded in this study, LBC certification is associated with a significantly
      lower discordant rate to both series and exact diagnosis for validated LBC
      ThinPrep preparations.

PMID- 16948512
TI  - Practical pathology of gunshot wounds.
AB  - CONTEXT: Gunshot wounds are the most common cause of homicidal death in the
      United States. Analysis and interpretation of fatal gunshot wounds is an
      important and common practice among forensic pathologists. Additionally, for
      pathology residents, it is an integral aspect of their training during their
      rotations at medical examiner or coroner offices. OBJECTIVE: The correct
      interpretation of gunshot wounds by forensic pathologists not only provides
      valuable information that can assist law enforcement in their investigation but
      also is essential for the final determination of manner of death. Discussion of
      the practical, basic, and essential skills required to interpret gunshot wounds
      include distinguishing a classic entrance wound from an exit wound; recognizing
      atypical entrance and exit wounds; utilizing the features of soot and stippling
      patterns to differentiate among contact, close, and distant range gunshot wounds;
      understanding of the trauma produced by gunshot wounds; and understanding the
      importance of recovering and documenting/handling any projectiles recovered at
      autopsy. DATA SOURCES: This article reviews numerous standard forensic pathology
      textbooks and the pertinent literature to formulate practical guidelines to
      assist the pathologist in the performance of forensic autopsies and the
      investigation of gunshot wound fatalities. CONCLUSIONS: Pathologists who perform
      investigations and autopsies to determine the cause and manner of death in
      gunshot wound cases must be aware of the implications, requirements, and pitfalls
      in interpretation of the injuries so that the examination fulfills its
      expectations to the community and the justice system.

PMID- 16948513
TI  - Elder maltreatment: a review.
AB  - CONTEXT: Elder maltreatment is not a new entity but is one that is recently
      recognized as a widespread and growing social problem. Unfortunately, few
      physicians are trained to recognize the different forms of elder maltreatment
      including physical abuse, sexual abuse, and neglect. The elder, age 65 years or
      older, is also a unique individual with respect to pathophysiology. The natural
      changes of aging must be considered when assessing any physical or laboratory
      findings. OBJECTIVE: The practicing pathologist and resident/fellow in training
      must be familiar with the 6 forms of elder abuse, in particular the 3 forms that
      are seen in general and forensic pathology: physical abuse, sexual abuse, and
      neglect. Naturally occurring conditions must also be recognized so that these are
      not erroneously interpreted as trauma or neglect. Furthermore, the victims and
      perpetrators, scenarios and risk factors, common anatomic and clinical findings,
      the pathophysiology of aging, and possible imitators of abuse must be understood.
      DATA SOURCES: This review explores the current medical and psychological
      understanding of elder maltreatment. Current scientific literature including peer
      reviewed journal publications and texts is cited. CONCLUSIONS: As a prevalent
      form of domestic violence, we can only expect to see more cases of elder
      maltreatment as the number and percentage of elders in our population increase.
      The correct interpretation of physical and laboratory findings is needed to
      adequately classify these cases, certify the cause and manner of death, and
      prevent future incidents.

PMID- 16948514
TI  - Hypothermia and hyperthermia medicolegal investigation of morbidity and mortality
      from exposure to environmental temperature extremes.
AB  - CONTEXT: The determination of the cause of death from exposure to extreme
      temperatures is a diagnosis of exclusion. Because both clinical and autopsy
      findings are nonspecific, a thorough investigation of the background and scene,
      evaluation of temporally relevant environmental conditions, and assessment of the
      victim's underlying state of health with appropriate laboratory studies, which
      frequently include autopsy, are essential to establish the cause of injury and/or
      death with reasonable medical probability. Individuals may encounter
      environmental extremes in many settings during any season. Both constitutional
      and external factors exacerbate the stress brought about by extreme temperature.
      OBJECTIVE: This article reviews guidelines for forensic investigation into
      environmental temperature extremes that contribute to an important seasonal
      grouping of morbidity and mortality in the United States. DATA SOURCES: Articles
      on clinical and pathologic aspects of hyperthermia and hypothermia were collected
      and reviewed. CONCLUSIONS: Recognition of multiple risk factors predisposing
      humans to both cold-related and heat-related morbidity and mortality enhances
      prevention. Awareness of the susceptibility of these exposed at-risk individuals
      is crucial to investigations by both clinicians and medicolegal death
      investigators.

PMID- 16948515
TI  - The art of attorney interaction and courtroom testimony.
AB  - CONTEXT: In our society it is well for a physician to know something of the
      workings of court and how to interact with attorneys. One need not go to law
      school to successfully navigate a legal proceeding as a physician witness.
      OBJECTIVE: To show that a physician skilled at interacting with colleagues and
      patients can successfully apply those skills to interacting with attorneys and
      testifying in court. DATA SOURCES: This work is based primarily on the author's
      experience in interacting with attorneys and testifying in court, with
      supplemental contributions from textbooks. CONCLUSIONS: Skillful testifying is
      simply the transmission of medical information in court in a professional,
      polite, and compelling manner, an ability within the grasp of any physician who
      has mastered the art of working with colleagues and patients. Careful, honest
      assessment of the medical matters in a legal case places a physician in a strong
      position, which the physician can maintain by remaining polite, even in the face
      of attempts by an attorney to denigrate the physician's professional abilities.
      The best witnesses tell the truth in a manner that compels people in the
      courtroom to listen.

PMID- 16948516
TI  - Upper aerodigestive tract squamous dysplasia: correlation with p16, p53, pRb, and
      Ki-67 expression.
AB  - CONTEXT: Differential expression of cell cycle-associated proteins may correlate
      with human papillomavirus status and may help delineate degree of dysplasia in
      upper aerodigestive tract squamous lesions. OBJECTIVE: To determine
      intraepithelial height of immunohistochemical staining for p16, p53, pRb, and Ki
      67 in upper aerodigestive tract lesions with reference to degree of dysplasia.
      Human papillomavirus status was ascertained to correlate with p16 expression.
      DESIGN: Biopsy specimens of 53 squamous dysplastic and 13 keratotic/hyperplastic
      lesions were immunohistochemically stained for p16, p53, pRb, and Ki-67. Mean
      height and proportion of positive staining were quantified and compared for
      keratotic/hyperplastic, mild, moderate, and severe dysplasia/carcinoma in situ.
      DNA extracted from paraffin-embedded blocks was evaluated for human
      papillomavirus by polymerase chain reaction amplification using consensus primers
      for mucosal viral types. RESULTS: Height of Ki-67 staining within the epithelium
      increased significantly between mild and moderate and between mild and severe
      dysplasia, with a trend toward increasing height between moderate and severe
      dysplasia. The percentage of cases with p16 staining decreased significantly with
      increasing degree of dysplasia; however, no significant trend in staining height
      or proportion was observed with p16, p53, or pRb in relation to degree of
      dysplasia, or between dysplastic and keratotic/hyperplastic lesions. Only 1 of 53
      dysplastic lesions was positive for human papillomavirus. CONCLUSIONS: This
      series of upper airway dysplastic mucosal lesions demonstrated a positive
      correlation between intraepithelial Ki-67 staining height and degree of
      dysplasia, offering a diagnostic aid in delineating degree of dysplasia in
      difficult squamous lesions.

PMID- 16948517
TI  - CD10 expression in cutaneous adnexal neoplasms and a potential role for
      differentiating cutaneous metastatic renal cell carcinoma.
AB  - CONTEXT: Recent investigations have demonstrated the utility of CD10 as a marker
      for renal cell carcinoma (RCC). Cutaneous metastases occur in up to 11% of
      patients with RCC and may be the presenting sign of widespread disease. The
      differential diagnosis in histopathologic evaluation of these cases includes
      cutaneous adnexal neoplasms, and describing the expression of CD10 in these
      tumors may be helpful in delineating the differential diagnosis. OBJECTIVE: To
      determine CD10 expression in a variety of adnexal lesions and to determine the
      diagnostic utility of CD10 in an immunohistochemical panel differentiating
      metastatic cutaneous renal cell carcinoma from cutaneous adnexal neoplasms.
      DESIGN: We studied 57 primary adnexal neoplasms of eccrine (n = 31), apocrine (n
      = 16), and sebaceous (n = 10) differentiation as well as normal skin (n = 3) and
      RCC metastatic to the skin (n = 4). A CD10 monoclonal antibody was applied to
      formalin-fixed, paraffin-embedded tissue. Specimens were randomized and
      categorized as immunopositive or immunonegative by a pathologist with expertise
      in immunohistochemistry who was blinded to the diagnoses. RESULTS: Two (6.5%) of
      31 eccrine, 1 (6%) of 16 apocrine, and 4 (40%) of 10 sebaceous neoplasms
      demonstrated CD10 immunopositivity. Four (100%) of 4 RCC were CD10
      immunopositive. CD10 expression was significant for eccrine and apocrine
      neoplasms (P < .001) compared to metastatic RCC, but not for sebaceous neoplasms
      (P = .08). CONCLUSION: Based on these results, CD10 is a useful additional
      immunostain for the discrimination of RCC metastatic to the skin and cutaneous
      adnexal neoplasms with eccrine and apocrine differentiation, but not with
      sebaceous differentiation.

PMID- 16948518
TI  - Distinct expression patterns of E-cadherin and beta-catenin in signet ring cell
      carcinoma components of primary pulmonary adenocarcinoma.
AB  - CONTEXT: E-Cadherin and beta-catenin complexes have been suggested to have
      critical roles in cancer development and progression. Primary signet ring cell
      carcinoma (SRCC) of the lung is a rare variant of pulmonary adenocarcinoma, and E
      cadherin and beta-catenin expressions of this tumor have not been documented, to
      our knowledge. OBJECTIVE: To characterize the E-cadherin and beta-catenin
      expressions in SRCC of the lung. DESIGN: An immunohistochemical evaluation of E
      cadherin and beta-catenin expressions in 10 cases of SRCC of the lung, 10 cases
      of conventional pulmonary adenocarcinoma, 10 cases of gastric SRCC, and 10 cases
      of colorectal SRCC was performed. RESULTS: Membranous E-cadherin and beta-catenin
      expressions were frequently reduced or absent in all types of tumors tested.
      Aberrant E-cadherin localization and nuclear beta-catenin accumulation were
      frequently found in gastric (6/10 and 5/10, respectively) and colorectal (7/10
      and 9/ 10, respectively) SRCCs, whereas SRCC of the lung rarely showed aberrant E
      cadherin localization (1/10) or nuclear beta-catenin accumulation (0/10).
      CONCLUSIONS: Signet ring cell carcinoma of the lung rarely showed aberrant E
      cadherin localization or beta-catenin nuclear accumulation, which are frequent
      events in gastric and colorectal SRCCs. These results suggest that the biologic
      roles of E-cadherin and beta-catenin complexes in SRCC of the lung differ from
      their roles in gastric or colorectal SRCCs.

PMID- 16948520
TI  - Mre11 expression in atypical adenomatous hyperplasia and adenocarcinoma of the
      lung.
AB  - CONTEXT: The Mre11-Rad50-NBS1 complex plays an important role in telomere
      maintenance. Recently, it has been proposed that alterations in Mre11 function
      may be contributing factors in the development of some tumors. Moreover,
      mutations of Mre11 have been demonstrated to cause reduced Mre11 immunostaining.
      OBJECTIVE: To investigate Mre11 in atypical adenomatous hyperplasia (AAH) and
      nonmucinous bronchioloalveolar carcinoma (NMBAC), an issue not previously
      explored. DESIGN: We examined (1) the expression of Mre11 protein in 27 AAHs (9
      lesions interpreted as low-grade AAH and 18 as high-grade AAH) and 40 NMBACs
      (using immunohistochemistry) and (2) Mre11 mRNA expression in 1 high-grade AAH
      and 6 NMBACs (using reverse transcription polymerase chain reaction). For the
      analysis of immunoreactivity, the intensity and extent of staining were each
      scored from 0 to 3. These 2 scores were summed to give in each case a final score
      of 0 to 6. RESULTS: Scores for Mre11 expression were 5.0 +/- 2.1 for low-grade
      AAH, 5.4 +/- 1.2 for high-grade AAH, and 5.5 +/- 0.9 for NMBAC, and there was no
      statistically significant difference among these 3 types of lesions. In the
      reverse transcription polymerase chain reaction for Mre11 mRNA, polymerase chain
      reaction products were detected in all samples. CONCLUSIONS: On this basis, we
      suggest that the part played by Mre11 in telomere maintenance may not be
      important for the progression of the adenoma-carcinoma (AAH-NMBAC) sequence in
      the lung, although some role for it in carcinogenesis cannot be completely ruled
      out.

PMID- 16948519
TI  - Combination of D-dimer and amino-terminal pro-B-type natriuretic Peptide testing
      for the evaluation of dyspneic patients with and without acute pulmonary
      embolism.
AB  - CONTEXT: D-dimer concentration can be used to exclude a diagnosis of acute
      pulmonary embolism. However, clinicians frequently order unnecessary supplemental
      testing in patients with low concentrations of D-dimer. Elevations in natriuretic
      peptides have also been described in the setting of pulmonary embolism.
      OBJECTIVE: We investigated the integrative role of D-dimer with amino-terminal
      pro-B-type natriuretic peptide for the evaluation of patients with and without
      acute pulmonary embolism. DESIGN: Patients were selected for analysis from a
      previous study in which levels of D-dimer and amino-terminal pro-B-type
      natriuretic peptide were measured. The presence of pulmonary embolism was
      determined by computed tomographic angiography. RESULTS: The median levels of D
      dimer were significantly higher in patients with acute pulmonary embolism.
      Similarly, the median levels of amino-terminal pro-B-type natriuretic peptide
      were higher in patients with pulmonary embolism. CONCLUSIONS: The Roche Tina
      quant D-Dimer immunoturbidimetric assay provides a high negative predictive value
      and can be used to exclude acute pulmonary embolism in patients with dyspnea.
      Measurement of amino-terminal pro-B-type natriuretic peptide in addition to D
      dimer improves specificity for acute pulmonary embolism without sacrificing
      negative predictive value. A combination of both markers may offer reassurance
      for excluding acute pulmonary embolism, and thus avoid redundant, expensive
      confirmatory tests.

PMID- 16948521
TI  - Documentation of surgical specimens using digital video technology.
AB  - CONTEXT: Digital technology is commonly used for documentation of specimens in
      anatomic pathology and has been mainly limited to still photographs. Technologic
      innovations, such as digital video, provide additional, in some cases better,
      options for documentation. OBJECTIVE: To demonstrate the applicability of digital
      video to the documentation of surgical specimens. DESIGN: A Canon Elura MC40
      digital camcorder was used, and the unedited movies were transferred to a
      Macintosh PowerBook G4 computer. Both the camcorder and specimens were hand-held
      during filming. The movies were edited using the software iMovie. Annotations and
      histologic photographs may be easily incorporated into movies when editing, if
      desired. RESULTS: The finished movies are best viewed in computers which contain
      the free program QuickTime Player. Movies may also be incorporated onto DVDs, for
      viewing in standard DVD players or appropriately equipped computers. The final
      movies are on average 2 minutes in duration, with a file size between 2 and 400
      megabytes, depending on the intended use. Because of file size, distribution is
      more practical via CD or DVD, but movies may be compressed for distribution
      through the Internet (e-mail, Web sites) or through internal hospital networks.
      CONCLUSIONS: Digital video is a practical, easy, and affordable methodology for
      specimen documentation, permitting a better 3-dimensional understanding of the
      specimens. Discussions with colleagues, student education, presentation at
      conferences, and other educational activities can be enhanced with the
      implementation of digital video technology.

PMID- 16948522
TI  - Diagnostic molecular pathology: an increasingly indispensable tool for the
      practicing pathologist.
AB  - CONTEXT: Diagnostic molecular pathology is rapidly becoming an indispensable tool
      for anatomic pathologists. Familiarity with some of the technologic principles
      and current, as well as upcoming, molecular diagnostic applications is greatly
      advantageous for today's practice of pathology. OBJECTIVES: To provide a
      discussion of the most common techniques currently used in molecular pathology
      laboratories and review their essential applications to diagnosis and management
      of neoplastic diseases. DATA SOURCES: A literature review and illustrative cases
      from the authors' molecular diagnostic practices. CONCLUSIONS: Applications such
      as clonality assays, molecular cytogenetics, and chimerism analysis are providing
      us with accurate tools to resolve difficult diagnostic and management decisions
      in hemato-oncology. This should serve as a future model to expand molecular
      applications into the wider field of solid tumors.

PMID- 16948523
TI  - "Benign," metastasizing adenomyoepithelioma of the breast: a report of 2 cases.
AB  - Adenomyoepitheliomas of the breast are rare tumors composed of a proliferation of
      2 cell populations. For the most part, they are considered to be benign, but they
      locally recur. Those neoplasms that metastasize are deemed to have come from a
      histologically malignant primary tumor. Herein, we describe 2 cases of metastases
      of histologically "benign" adenomyoepitheliomas of the breast to the lung. In
      both cases, the primary neoplasms and the metastases did not show histologic
      features of malignancy. These unique cases represent another example of neoplasms
      that can metastasize in the absence of histologic features that would suggest
      malignant behavior. Establishing the diagnosis, determining optimal therapy, and
      predicting outcome are problematic because of the rarity of this entity. Perhaps,
      classification of adenomyoepitheliomas should be changed to recognize those
      neoplasms with malignant behavior.

PMID- 16948524
TI  - Are gadolinium-based contrast media nephrotoxic? A renal biopsy study.
AB  - Gadolinium-based contrast media were originally introduced as alternatives to
      iodinated media for magnetic resonance imaging. Although originally thought to be
      nonnephrotoxic, gadolinium-based contrast media have recently been reported to be
      associated with acute renal failure; the mechanism and the underlying renal
      injury are not completely understood. We report what is, to our knowledge, the
      first renal biopsy in this context. A 56-year-old patient underwent 2 consecutive
      vascular imaging procedures in conjunction with gadolinium-based contrast medium
      administration. A few days later, the patient developed acute renal failure. A
      renal biopsy showed acute tubular cell injury including patchy tubular cell
      necrosis, tubular cell degeneration, and marked proliferation of tubular cells,
      together with mild interstitial edema and interstitial inflammation, but without
      significant glomerular or vascular changes. During supportive therapy, renal
      function was partially regained. This case emphasizes the potential
      nephrotoxicity of gadolinium-based contrast media and suggests that the
      nephrotoxicity is related to potentially reversible acute tubular cell injury.

PMID- 16948525
TI  - Low-grade fibromyxoid sarcoma: a brief review.
AB  - Low-grade fibromyxoid sarcomas are uncommon deep soft tissue neoplasms first
      described by Evans in 1987. They exhibit a deceptively benign appearance, with a
      whorled or linear arrangement of spindle-shaped cells showing few to absent
      mitoses. A characteristic, but not specific, feature is the presence of areas of
      myxoid stroma. Recurrences are common, and late metastases have been recorded. A
      closely related but morphologically distinct tumor, the so-called hyalinizing
      spindle cell tumor with giant rosettes, has also been described; both neoplasms
      share the same cytogenetic abnormality, a balanced translocation resulting in a
      FUS/CREB3L2 fusion gene. Because of similar clinical behavior and the common
      cytogenetic abnormality, some authors prefer to consider both lesions as a single
      entity within the spectrum of low-grade sarcomas.

PMID- 16948528
TI  - Evidence of influence of genomic DNA sequence on human X chromosome inactivation.
AB  - A significant number of human X-linked genes escape X chromosome inactivation and
      are thus expressed from both the active and inactive X chromosomes. The basis for
      escape from inactivation and the potential role of the X chromosome primary DNA
      sequence in determining a gene's X inactivation status is unclear. Using a
      combination of the X chromosome sequence and a comprehensive X inactivation
      profile of more than 600 genes, two independent yet complementary approaches were
      used to systematically investigate the relationship between X inactivation and
      DNA sequence features. First, statistical analyses revealed that a number of
      repeat features, including long interspersed nuclear element (LINE) and mammalian
      wide interspersed repeat repetitive elements, are significantly enriched in
      regions surrounding transcription start sites of genes that are subject to
      inactivation, while Alu repetitive elements and short motifs containing ACG/CGT
      are significantly enriched in those that escape inactivation. Second, linear
      support vector machine classifiers constructed using primary DNA sequence
      features were used to correctly predict the X inactivation status for >80% of all
      X-linked genes. We further identified a small set of features that are important
      for accurate classification, among which LINE-1 and LINE-2 content show the
      greatest individual discriminatory power. Finally, as few as 12 features can be
      used for accurate support vector machine classification. Taken together, these
      results suggest that features of the underlying primary DNA sequence of the human
      X chromosome may influence the spreading and/or maintenance of X inactivation.

PMID- 16948529
TI  - Striking similarities in the genomic distribution of tandemly arrayed genes in
      Arabidopsis and rice.
AB  - In Arabidopsis, tandemly arrayed genes (TAGs) comprise >10% of the genes in the
      genome. These duplicated genes represent a rich template for genetic innovation,
      but little is known of the evolutionary forces governing their generation and
      maintenance. Here we compare the organization and evolution of TAGs between
      Arabidopsis and rice, two plant genomes that diverged ~150 million years ago.
      TAGs from the two genomes are similar in a number of respects, including the
      proportion of genes that are tandemly arrayed, the number of genes within an
      array, the number of tandem arrays, and the dearth of TAGs relative to single
      copy genes in centromeric regions. Analysis of recombination rates along rice
      chromosomes confirms a positive correlation between the occurrence of TAGs and
      recombination rate, as found in Arabidopsis. TAGs are also biased functionally
      relative to duplicated, nontandemly arrayed genes. In both genomes, TAGs are
      enriched for genes that encode membrane proteins and function in "abiotic and
      biotic stress" but underrepresented for genes involved in transcription and DNA
      or RNA binding functions. We speculate that these observations reflect an
      evolutionary trend in which successful tandem duplication involves genes either
      at the end of biochemical pathways or in flexible steps in a pathway, for which
      fluctuation in copy number is unlikely to affect downstream genes. Despite
      differences in the age distribution of tandem arrays, the striking similarities
      between rice and Arabidopsis indicate similar mechanisms of TAG generation and
      maintenance.

PMID- 16948530
TI  - Model-based design of growth-attenuated viruses.
AB  - Live-virus vaccines activate both humoral and cell-mediated immunity, require
      only a single boosting, and generally provide longer immune protection than
      killed or subunit vaccines. However, growth of live-virus vaccines must be
      attenuated to minimize their potential pathogenic effects, and mechanisms of
      attenuation by conventional serial-transfer viral adaptation are not well
      understood. New methods of attenuation based on rational engineering of viral
      genomes may offer a potentially greater control if one can link defined genetic
      modifications to changes in virus growth. To begin to establish such links
      between genotype and growth phenotype, we developed a computer model for the
      intracellular growth of vesicular stomatitis virus (VSV), a well-studied,
      nonsegmented, negative-stranded RNA virus. Our model incorporated established
      regulatory mechanisms of VSV while integrating key wild-type infection steps:
      hijacking of host resources, transcription, translation, and replication,
      followed by assembly and release of progeny VSV particles. Generalization of the
      wild-type model to allow for genome rearrangements matched the experimentally
      observed attenuation ranking for recombinant VSV strains that altered the genome
      position of their nucleocapsid gene. Finally, our simulations captured previously
      reported experimental results showing how altering the positions of other VSV
      genes has the potential to attenuate the VSV growth while overexpressing the
      immunogenic VSV surface glycoprotein. Such models will facilitate the engineering
      of new live-virus vaccines by linking genomic manipulations to controlled changes
      in virus gene-expression and growth.

PMID- 16948532
TI  - Oriented scanning is the leading mechanism underlying 5' splice site selection in
      mammals.
AB  - Splice site selection is a key element of pre-mRNA splicing. Although it is known
      to involve specific recognition of short consensus sequences by the splicing
      machinery, the mechanisms by which 5' splice sites are accurately identified
      remain controversial and incompletely resolved. The human F7 gene contains in its
      seventh intron (IVS7) a 37-bp VNTR minisatellite whose first element spans the
      exon7-IVS7 boundary. As a consequence, the IVS7 authentic donor splice site is
      followed by several cryptic splice sites identical in sequence, referred to as 5'
      pseudo-sites, which normally remain silent. This region, therefore, provides a
      remarkable model to decipher the mechanism underlying 5' splice site selection in
      mammals. We previously suggested a model for splice site selection that, in the
      presence of consecutive splice consensus sequences, would stimulate exclusively
      the selection of the most upstream 5' splice site, rather than repressing the 3'
      following pseudo-sites. In the present study, we provide experimental support to
      this hypothesis by using a mutational approach involving a panel of 50 mutant and
      wild-type F7 constructs expressed in various cell types. We demonstrate that the
      F7 IVS7 5' pseudo-sites are functional, but do not compete with the authentic
      donor splice site. Moreover, we show that the selection of the 5' splice site
      follows a scanning-type mechanism, precluding competition with other functional
      5' pseudo-sites available on immediate sequence context downstream of the
      activated one. In addition, 5' pseudo-sites with an increased complementarity to
      U1snRNA up to 91% do not compete with the identified scanning mechanism.
      Altogether, these findings, which unveil a cell type-independent 5'-3'-oriented
      scanning process for accurate recognition of the authentic 5' splice site,
      reconciliate apparently contradictory observations by establishing a hierarchy of
      competitiveness among the determinants involved in 5' splice site selection.

PMID- 16948539
TI  - Celiac disease in the adult.

PMID- 16948531
TI  - Yersinia has a tropism for B and T cell zones of lymph nodes that is independent
      of the type III secretion system.
AB  - Pathogenic Yersinia have a pronounced tropism for lymphatic tissues and harbor a
      virulence plasmid that encodes a type III secretion system, pTTSS, that
      transports Yops into host cells. Yops are critical virulence factors that prevent
      phagocytosis by macrophages and neutrophils and Yersinia mutants lacking one or
      more Yops are defective for survival in lymphatic tissues, liver, and
      gastrointestinal tract. However, here we demonstrate that Y. pseudotuberculosis
      (Yptb) mutants lacking the pTTSS survived as well as or better than wild-type
      (WT) Yptb in the mesenteric lymph nodes (MLN). Infection with pTTSS mutants
      caused lymphadenitis with little necrosis, whereas infection with WT Yptb
      provoked lymphadenitis with multiple necrotic suppurative foci. Gentamicin
      protection assays and microscopic examination of the MLN revealed that pTTSS
      mutants resided extracellularly adjacent to B and T lymphocytes in the cortex and
      paracortex. WT Yptb was found extracellularly adjacent to neutrophils and
      macrophages in necrotic areas and adjacent to B and T lymphocytes in less
      inflamed areas. To determine whether lymphocytes protected pTTSS mutants from
      phagocytic cells, Rag1(-/-) mice were infected with pTTSS mutants or WT Yptb.
      pTTSS mutants but not WT, were impaired for survival in MLN of Rag1(-/-) mice,
      suggesting that lymphocyte-rich regions constitute a protective niche for pTTSS
      mutants. Finally, we show that invasin and the chromosomally encoded TTSS were
      not required for Yptb survival in MLN. In summary, chromosomally encoded factors
      are sufficient for Yptb replication in the cortex and paracortex of MLN; the
      pTTSS enables Yersinia to survive within phagocyte-rich areas of lymph nodes, and
      spread to other tissues.

PMID- 16948540
TI  - Current epidemiology and accessibility to diet compliance in adult celiac
      disease.
AB  - BACKGROUND: The widespread of serologic diagnosis for celiac disease has brought
      about an epidemiologic shift. Little up-to-date information is available on
      relevant epidemiologic issues regarding diagnosis, information, and therapy.
      OBJECTIVE: To examine forms of presentation, diagnostic difficulties, follow-up,
      information sources, and treatment-related issues regarding celiac disease.
      METHOD: A cross-sectional observational study using a self-completed
      questionnaire. RESULTS: Seventy-three adult patients were included; 15.0% of
      cases were diagnosed over 60 years of age. Most were non-smokers (91.8%). The
      rate of first-degree relatives with celiac sprue was 10.9%. The disease had a
      classic presentation in only 54.7% of cases. A functional gastrointestinal
      disorder was initially suspected in 42.4% of patients. Diet adherence is
      adequate, with unintentional lack of compliance in 15.5% of patients. Diet
      results in absent or improved symptoms in virtually all patients, but most of
      them consider compliance a challenge. Forty percent had difficulty finding gluten
      free food, and 50.8% had problems in labelling recognition. CONCLUSIONS: Celiac
      disease presents at any age, has a great variety of manifestations, and responds
      very well to gluten-free diet. It is crucial that patients be highly motivated
      and informed, and that they know for certain which foods and manufactured
      products are to be to used. Therefore, adequate control will result from
      coordination and cooperation regarding all resources involved, including medical
      care, and information provided by associations and other sources such as the Web.

PMID- 16948541
TI  - Restorative proctocolectomy with an ileoanal pouch: the role of laparoscopy.
AB  - OBJECTIVES: The Aim of this retrospective study was to evaluate early experience
      with laparoscopic restorative proctocolectomy by analyzing the perioperative
      results of surgical treatment. PATIENTS AND METHODS: Seven major surgeries were
      performed in six patients with familial adenomatous polyposis and ulcerative
      colitis. All procedures were performed under laparoscopy at our third-level
      hospital from June 2003 to October 2004. RESULTS: Mean surgical time was 287.5 +/
      80.7 min, and median blood loss was 300 +/- 249.0 cc. There were no conversions;
      return of peristalsis began at 32 +/- 12.4 h; average time to first oral intake
      was 64.0 +/- 32.8 h, and mean duration of hospital stay was 9.3 +/- 1.2 days.
      There was one case of perineal sepsis due to ileal pouch-anal anastomotic
      leakage, which was successfully treated with oral intake restriction, parenteral
      nutrition, and intra-rectal drainage. The most common postoperative complication
      was postoperative ileus. CONCLUSIONS: We believe that the laparoscopic approach
      to restorative proctocolectomy may be considerably improved in our center.
      Particular aspects for improvement include efforts to achieve lower operating and
      hospitalization times to equate our results with those reported by multicenter
      studies for laparoscopic colon cancer surgery. In our opinion, learning and
      further training opportunities should be encouraged to improve surgeon experience
      in the field of laparoscopy, preferably at centers specializing in restorative
      proctocolectomy.

PMID- 16948542
TI  - 20 years experience in the management of Zenker's diverticulum in a third-level
      hospital.
AB  - Zenker s diverticulum arises in the posterior wall of the pharynx, above the
      cricopharyngeal muscle, secondary to a functional cricopharyngeal disorder. We
      describe our experience with the management of Zenker s diverticulum from 1985 to
      this day in a third-level hospital. We review clinical data from 27 patients (78%
      males) with a mean age of 60.4 years. The most common clinical manifestations
      were dysphagia, regurgitation, syalorrhea, cough, and weight loss. All cases were
      diagnosed using an esophagogram. A diverticulectomy with cricopharingeal myotomy
      was performed in 74% of patients. Complications developed in 5 cases (21%), and
      the recurrence rate was 4% (1 of 3 cases, where myotomy was not performed).

PMID- 16948543
TI  - Public opinion survey after capsule endoscopy: patient s point of view on its
      utility.
AB  - AIM: When programming a medical test such as capsule endoscopy (CE), finding the
      closest point between the patient's experience and his/her expectation is
      essential to improve any further explorations. For this purpose we designed a
      form which tries to collect the information required. MATERIAL AND METHODS: From
      December 2003 to January 2005 we examined the small intestine of 98 patients with
      the help of CE. Later they were sent an anonymous questionnaire in July 2005,
      which included 10 questions upon the origin and previous knowledge of the patient
      about this technique, their tolerance to it, and the value they attached to it
      with regard to finding a new diagnosis and assigning different treatments, and
      also the incidence in the positive or negative evolution of their disease in
      particular and of medicine in general. RESULTS: Answer rate reached 58% and was
      slightly higher among women and people over 70 years; 80% of repliers had been
      informed about CE by a physician, while nearly all the rest had received previous
      information from the media; 37% had had symptoms for more than 12 months, while
      only 17% had suffered them for one month before the exploration. A bit over 30%
      did not know what the specific diagnostic field of the test was (most of them
      women and young people), although most of them were not surprised by the
      procedure. Over 75% showed "acceptable" or "excellent" tolerance, while 5.5%
      (most of them young people) found it hard to bear. The opinion about its utility
      in the diagnosis was 37%, and although 70% thought that CE had revealed nothing
      new about their pathology, over 60% declared feeling better after the test; 84%
      pointed out that it had achieved a breakthrough for their quality of life (most
      of them men and very old people), and only 13% thought it was worthless. However,
      nearly all the answers agreed in that CE was an "important" or "very important"
      diagnostic device. CONCLUSIONS: After the test using CE, the diagnostic benefit
      detected by the patient is not the same as that shown by technical studies.
      Nevertheless, the test can be highly satisfactory for the patient in particular,
      and also in an overall view. CE is a well-tolerated test, applied in our setting
      to chronic diseases and that, contrary to what we supposed, is explained to
      patients mainly by a physician. Most of them are not familiar with its specific
      indications.

PMID- 16948544
TI  - Constipation in the population over 50 years of age in Albacete province.
AB  - OBJECTIVE: To Determine the incidence of constipation in Albacete province and
      its relation with diet and lifestyle. PATIENTS AND METHODS: Cross-sectional
      population survey. We studied 414 participants over 50 years of age in Albacete
      province. 445 persons over 50 years of age were included in the study. All
      participants were selected by systematic random sampling; 414 participants filled
      in the questionnaire correctly. MAIN MEASURES: age, weight and height, marital
      status, level of education and occupation; presence of a disease, number of sleep
      hours a day, physical exercise, smoking, alcohol intake, drug intake (anti
      inflammatories and laxatives); bowel habit, diet, meal frequency and place; food
      intake frequency per week, daily intake of water, coffee, tea and herbal
      beverages; vitamin and fiber supplements; presence of cancer in the family.
      RESULTS: 56.9% of participants were women. Mean age 67.07 years. In Albacete
      province, 4.4% of the population over 50 years have a bowel habit consistent with
      constipation. Most participants had three meals a day (breakfast, lunch, and
      supper), while 50% had another meal in the morning or afternoon. These meals took
      place, habitually, in the domicile. There was a preponderance in daily intake of
      the following foods: milk (83.7%), bread (95.1%), vegetables (68.8%), fruit
      (91.8%), and virgin olive oil (96.6%). Fish was eaten every one to two days, and
      pulses and meat every three to six days. 44.4% of participants drank one to two
      liters of water a day. Only 3.9% of participants took some supplement; 35% of
      participants were on a diet. It was observed that 97.7% of participants with more
      than three defecations a week had a high intake of virgin olive oil; 65.7% of
      participants did some physical exercise customarily; 70.2% of participants were
      non-smokers, 10.2% were smokers, and 18.4% were ex-smokers. With regard to
      alcohol, the percentage of drinkers was 35.1%. The main class of medications
      taken by participants was NSAIDs - 14.5%; 79.7% took neither NSAIDs nor
      laxatives. Only 2.7% of participants took laxatives regularly. CONCLUSIONS: Most
      participants had relatively healthy eating habits.

PMID- 16948545
TI  - Kupffer cells and alcoholic liver disease.
AB  - Liver disease is a major cause of illness and death worldwide. A central
      component in the complex network leading to the development of alcoholic liver
      disease is the activation of Kupffer cells by endotoxin and other soluble
      mediators. Alcohol consumption induces a state of "leaky gut increasing plasma
      and liver endotoxin levels. When Kupffer cells become activated, they interact
      with a complex of proteins located on the extracellular membrane signaling to
      produce a wide array of soluble factors, including cytokines, chemokines, growth
      factors, cyclooxygenase and lipoxygenase metabolites, and reactive oxygen species
      such as superoxide anion, hydrogen peroxide, and nitric oxide, all of which
      provide physiologically diverse and pivotal paracrine effects on all other liver
      cell types and, ultimately, liver injury. Kupffer cells are also central to the
      liver homeostatic response to injury as upon cellular degenerative changes, they
      immediately respond to the insult and release mediators to orchestrate
      inflammatory and reparative responses. Thus, the homeostatic responses are
      initiated by Kupffer cell-derived mediators at the cellular level and underlie
      the liver s defense and reparative mechanisms against injury. In order to
      understand better the role of Kupffer cells in the onset of liver injury, animal
      models in which Kupffer cells are inactivated, and cell culture settings (e.g. co
      cultures) are being used with promising results that advance our understanding of
      alcoholic liver disease.

PMID- 16948546
TI  - Atypical left paraduodenal hernia.

PMID- 16948547
TI  - [Gastrointestinal bleeding as presentation of a testicular germ cell tumor].

PMID- 16948548
TI  - [Lymphocitic colitis and celiac disease].

PMID- 16948549
TI  - [Ileal intussusception due to inflammatory fibroid polyp].

PMID- 16948550
TI  - [Malignant leiomyoblastoma of the small bowel due to acute lower gastrointestinal
      bleeding].

PMID- 16948551
TI  - [Inflammatory fibroid polyp of the stomach].

PMID- 16948552
TI  - Alternative routes of influenza vaccine delivery.
AB  - The global emergence of virulent avian influenza and the concomitant raised
      threat of an influenza pandemic has increased interest in the development of
      improved influenza vaccines. Whereas conventional influenza vaccines are
      delivered by parenteral injection, an intranasal influenza vaccine has been
      marketed since 2003. Many other technologies are in development for intranasal,
      oral, epidermal and topical influenza vaccines. This editorial summarises the
      advances in clinical development of technologies for needle-free influenza
      vaccine delivery.

PMID- 16948553
TI  - pH-responsive shielding of non-viral gene vectors.
AB  - PEG shielding of non-viral vectors reduces undesired interactions with the
      extracellular environment. Combination with cell-binding domains enables in vivo
      targeting via specific attachment to the target cells. Pegylation, however, also
      interferes with effective intracellular nucleic acid delivery. Consistently
      triggered removal of the PEG shield after reaching the target cell would make non
      viral vectors more compatible with the intracellular delivery steps.
      Physiological triggers may include changes in pH, enzyme concentration or redox
      potential. This review focuses on pH-sensitive shielding strategies that exploit
      the endosomal acidification process after endocytosis for deshielding of the
      delivery system.

PMID- 16948554
TI  - Temperature- and pH-responsive smart polymers for gene delivery.
AB  - Biopolymer therapeutics are likely to be the next generation of medicines, and
      nucleic acids are among the most important of these potential drugs. The
      challenges of delivering genes are formidable and advanced biomimetic materials
      are expected to be required. Polymers that can respond to changes in temperature
      and pH are good candidates for gene delivery vehicles, as the stimulus response
      can be used to alter their interactions with the drug payload. In this review,
      the chemistries underlying these responsive polymers are considered, and the
      possible mechanisms by which nucleic acids, primarily DNA, can be protected
      during transit and released at target sites are outlined. Sophisticated
      multicomponent polymers are being developed, with functionalities designed to
      overcome the barriers to gene delivery at both the systemic and local level; key
      examples are highlighted. The extension of these materials to yet more advanced
      therapies, such as cell delivery and regenerative medicine, is outlined as an
      emerging technology for the future.

PMID- 16948555
TI  - Time-controlled oral delivery systems for colon targeting.
AB  - In recent years, many research efforts have been spent in the achievement of
      selective delivery of drugs into the colon following oral administration. Indeed,
      colonic release is regarded as a beneficial approach to the pharmacological
      treatment or prevention of widespread large bowel pathologies, such as
      inflammatory bowel disease and adenocarcinoma. In addition, it is extensively
      explored as a potential means of enhancing the oral bioavailability of peptides,
      proteins and other biotechnological molecules, which are known to be less prone
      to enzymatic degradation in the large, rather than in the small, intestine. Based
      on these premises, several formulation strategies have been attempted in pursuit
      of colonic release, chiefly including microflora-, pH-, pressure- and time
      dependent delivery technologies. In particular, this review is focused on the
      main design features and release performances of time-controlled devices, which
      rely on the relative constancy that is observed in the small intestinal transit
      time of dosage forms.

PMID- 16948556
TI  - Sublingual immunotherapy of allergic diseases.
AB  - The only disease-modifying treatment that is available for allergic patients is
      allergen-specific immunotherapy. Two competing application forms are used:
      subcutaneous immunotherapy, which has been used for > 90 years, and a relatively
      new immunotherapy where the allergen is applied sublingually. Numerous studies
      have shown efficacy for subcutaneous immunotherapy and have identified possible
      mechanisms that are responsible for the observed reduction in allergic responses.
      In contrast, the efficacy of sublingual immunotherapy has not been documented to
      the same degree and the responsible immunological mechanisms have not yet been
      clearly defined. This review focuses on the published clinical and experimental
      data on sublingual immunotherapy and points at possible mechanisms of how
      sublingual immunotherapy may differ from subcutaneous immunotherapy in its mode
      of action, and also discusses the potential advantages and pit falls of both
      therapies.

PMID- 16948557
TI  - Nanoparticulate drug carriers for delivery of HIV/AIDS therapy to viral reservoir
      sites.
AB  - Providing the optimum treatment of AIDS is a major challenge in the 21st Century.
      HIV is localised and harboured in certain inaccessible compartments of the body,
      such as the CNS, the cerebrospinal fluid, the lymphatic system and in the
      macrophages, where it cannot be reached by the majority of therapeutic agents in
      adequate concentrations or in which the therapeutic agents cannot reside for the
      necessary duration. Progression in HIV/AIDS treatment suggests that available
      therapy can lower the systemic viral load below the detection limit. However, on
      discontinuation of treatment, there is relapse of the infection from the
      reservoir sites and a potential for resistance development. This review discusses
      the aetiology and pathology of HIV, with emphasis on the viral reservoirs,
      current therapy of AIDS, and the opportunity for nanotechnology-based drug
      delivery systems to facilitate complete eradication of viral load from the
      reservoir sites. Literature-cited examples of drug delivery systems that are
      under investigation for the treatment of AIDS are discussed. The article also
      focuses on the future outlook and strategies for investigational drug
      formulations that use nanotherapeutic strategy for HIV/AIDS.

PMID- 16948558
TI  - Pharmaceutical nanotechnology: polymeric vesicles for drug and gene delivery.
AB  - Improving the therapeutic index of medicines is a goal of drug delivery.
      Employing nanosystems that control drug biodistribution is one way of achieving
      therapeutic improvements, and polymeric bilayer vesicles are one such nanosystem.
      Polymeric vesicles, with the ability to transport drugs or genes, are prepared in
      one of two ways: i) the self-assembly of amphiphilic polymers and ii) the
      polymerisation of monomers, following self-assembly (polymerised vesicles). There
      are two types of self-assembling amphiphilic polymers: water-soluble polymers
      derivatised with hydrophobic pendant groups and amphiphilic block copolymers.
      Amphiphilic alkenes and alkynes are the main compounds that are used to make
      polymerised vesicles. This review discusses polymer architecture fundamentals
      that govern the self-assembly of polymers into vesicles, the fine control on
      vesicle size that is achievable with polymeric vesicles and the application of
      the vesicles to drug delivery.

PMID- 16948559
TI  - Linear cyclodextrin-containing polymers and their use as delivery agents.
AB  - Cyclodextrins, cyclic oligomers of glucose, have been used in pharmaceutical
      formulations for decades as a result to their biocompatibilities, low toxicities
      and their abilities to solubilise organic small molecules via inclusion complex
      formation. The incorporation of cyclodextrins within polymers of numerous types,
      for use as drug delivery agents, has been explored. Illustrative of the
      flexibility in polymer chemistry and delivery application that is possible with
      these materials, two linear cyclodextrin-containing polymers are in preclinical
      and clinical development for the non-covalent delivery of nucleic acid
      therapeutics and covalent delivery of a small-molecule drug, respectively. This
      document provides an overview of the background and progress that has been made
      with these materials thus far, as well as suggestions for their future
      development and characterisation.

PMID- 16948561
TI  - Proprietary Rel-Ease drug delivery technology: opportunity for sustained delivery
      of peptides, proteins and small molecules.
AB  - Proprietary Rel-Ease (Praecis Pharmaceuticals) drug delivery technology uses
      biocompatible polymers as carriers to incorporate a drug into a polymer matrix
      through opposite charge interaction or complexation. The resulting low solubility
      complexes can be used to prepare sustained release depot injections or
      potentially sustained release formulations for oral administration. As a
      regulatory approved and commercialised drug delivery technology, Rel-Ease is used
      in abarelix for injectable suspension, a monthly depot injection for the
      treatment of patients with advanced prostate cancer. The technology offers high
      drug loading and minimal-to-no initial burst effect in vivo. It uses aqueous
      processes and is compatible for complexation with many peptide and protein
      therapeutics; its mechanism can also be applied to many small-molecule
      therapeutics and offers conventional and alternative methods for sustained
      release delivery via an oral route.

PMID- 16948562
TI  - Dose accuracy of a reusable insulin pen using a cartridge system with an
      integrated plunger mechanism.
AB  - Pen injection devices are a common method of administering insulin for patients
      with diabetes. Pen devices must comply with guidelines prepared by the
      International Organization for Standardization, which include device dose
      accuracy and precision. OptiClik (sanofi-aventis) was developed to fulfil unmet
      needs of patients with diabetes, including: easier cartridge changing, clearer
      dose display and readability, and a larger dose of insulin to be delivered with a
      single injection. In this paper, the authors report on the dose accuracy of the
      OptiClik pen device, which uses a novel cartridge system with an integrated
      plunger for easier cartridge changing. The authors show that OptiClik accurately
      delivers a required dose of insulin, which is maintained over the lifetime of the
      pen. OptiClik offers a significant contribution to the treatment of diabetes.

PMID- 16948563
TI  - Promoting absorption of drugs in humans using medium-chain fatty acid-based solid
      dosage forms: GIPET.
AB  - One of the most important and challenging goals in drug delivery is overcoming
      the poor oral absorption of high-value therapeutics that include peptides.
      Gastrointestinal Permeation Enhancement Technology (GIPET) attempts to address
      this question by safely delivering drugs across the small intestine in
      therapeutically relevant concentrations. GIPET is based primarily on promoting
      drug absorption through the use of medium-chain fatty acids, medium-chain fatty
      acid derivatives and microemulsion systems based on medium-chain fatty acid
      glycerides formulated in enteric-coated tablets or capsules. Importantly, these
      excipients are generally regarded as safe and the systems are formulated in such
      a way that there is no change in chemical composition of the active ingredient.
      More than 300 volunteers have been administered GIPET formulations in 16 Phase I
      studies of 6 separate drugs comprising both single- and repeat-dosing regimes.
      Oral bioavailability of alendronate, desmopressin and low-molecular-weight
      heparin in humans was increased using GIPET formulations compared with
      unformulated controls. GIPET was well tolerated by human subjects. Using fluxes
      of markers of epithelial permeability, the effects of GIPET on the human
      intestine were shown to be rapid, short-lived and reversible in vivo. These data
      suggest that GIPET formulations have genuine potential as a platform technology
      for safe and effective oral drug delivery of a wide range of poorly permeable
      drugs.

PMID- 16948564
TI  - New advances in aerosolised drug delivery: vibrating membrane nebuliser
      technology.
AB  - Innovative nebuliser systems bear the potential to greatly improve and expand the
      administration of therapeutic aerosols for the treatment of respiratory diseases.
      Exploiting the technology of a microperforated vibrating membrane offers a close
      control of the droplet size that is being generated and targeted to reach the
      lower airways, with little oropharyngeal deposition, thereby reducing undesired
      side effects. The greatly improved efficiency of such devices, as exemplified by
      the eFlow nebuliser (PARI), provides further advantages for the patient. A high
      respirable fraction due to the precisely defined perforations, low residual
      losses and the high liquid output rate combine to produce a highly efficient and
      fast administration of inhaled medications. Portability, ease of handling and
      noiseless operation have a positive effect on patient compliance, control of the
      therapy by the physician and the therapy costs.

PMID- 16948567
TI  - Requests additional information on infective endocarditis study.

PMID- 16948568
TI  - Principles of veterinary bioethics.

PMID- 16948560
TI  - Growth factor delivery for oral and periodontal tissue engineering.
AB  - The treatment of oral and periodontal diseases and associated anomalies accounts
      for a significant proportion of the healthcare burden, with the manifestations of
      these conditions being functionally and psychologically debilitating. Growth
      factors are critical to the development, maturation, maintenance and repair of
      craniofacial tissues, as they establish an extracellular environment that is
      conducive to cell and tissue growth. Tissue-engineering principles aim to exploit
      these properties in the development of biomimetic materials that can provide an
      appropriate microenvironment for tissue development. These materials have been
      constructed into devices that can be used as vehicles for delivery of cells,
      growth factors and DNA. In this review, different mechanisms of drug delivery are
      addressed in the context of novel approaches to reconstruct and engineer oral-
      and tooth-supporting structures, namely the periodontium and alveolar bone.

PMID- 16948569
TI  - Counseling veterinary students who aspire to careers in science.

PMID- 16948571
TI  - What is your diagnosis? Tetralogy of Fallot.

PMID- 16948570
TI  - What is your diagnosis? Dystocia.

PMID- 16948572
TI  - Animal behavior case of the month.

PMID- 16948573
TI  - Facilitative and functional fats in diets of cats and dogs.

PMID- 16948574
TI  - Requirements for mandatory reporting of animal cruelty.

PMID- 16948575
TI  - Lifelong diet restriction and radiographic evidence of osteoarthritis of the hip
      joint in dogs.
AB  - OBJECTIVE: To evaluate the effects of diet restriction on development of
      radiographic evidence of hip joint osteoarthritis in dogs. DESIGN: Longitudinal
      cohort study. ANIMALS: 48 Labrador Retrievers from 7 litters. PROCEDURES: Forty
      eight 6-week-old puppies from 7 litters were paired with littermates by sex and
      weight, and each pairmate was randomly assigned to 1 of 2 groups of 24 dogs each.
      Starting at 8 weeks of age, 1 group was fed ad libitum (control fed) and the
      other was fed 25% less (restricted fed) of the same diet for life on a pairwise
      basis. The dogs' hip joints were radiographed in the standard ventrodorsal hip
      extended view at multiple intervals prior to 1 year of age and at annual
      intervals thereafter on the basis of birth anniversary. A board-certified
      radiologist unaware of group assignment scored the radiographs for evidence of
      osteoarthritis. RESULTS: Prevalence of radiographic evidence of hip joint
      osteoarthritis in all dogs increased linearly throughout the study, from an
      overall prevalence of 15% at 2 years to 67% by 14 years. Restricted-fed dogs had
      lower prevalence and later onset of hip joint osteoarthritis. Median age at first
      identification of radiographic evidence of hip joint osteoarthritis was
      significantly lower in the control-fed group (6 years), compared with the
      restricted-fed group (12 years). CONCLUSIONS AND CLINICAL RELEVANCE: Restricted
      feeding delayed or prevented development of radiographic signs of hip joint
      osteoarthritis in this cohort of Labrador Retrievers. Lifetime maintenance of 25%
      diet restriction delayed onset and reduced severity of hip joint osteoarthritis,
      thus favorably affecting both duration and quality of life. In addition, the data
      indicated that development of hip joint osteoarthritis was not bimodal in these
      dogs but occurred as a continuum throughout life.

PMID- 16948576
TI  - Development of antimicrobial drug resistance in rectal Escherichia coli isolates
      from dogs hospitalized in an intensive care unit.
AB  - OBJECTIVE: To determine whether duration of hospitalization in the intensive care
      unit (ICU) of a veterinary teaching hospital was associated with prevalence of
      antimicrobial resistance among rectal Escherichia coli isolates from dogs,
      whether antimicrobial treatment was associated with prevalence of antimicrobial
      resistance, and whether there were associations among antimicrobial drugs to
      which isolates were resistant. DESIGN: Prospective observational study. ANIMALS:
      116 dogs hospitalized in an ICU for >or= 3 days. PROCEDURES: Rectal swab
      specimens were obtained every 3 days and submitted for bacterial culture for E
      coli. Isolates were tested for susceptibility to 12 antimicrobial agents by means
      of disk diffusion. RESULTS: For each additional day that a dog was hospitalized
      in the ICU, the odds of being colonized with an E coli isolate resistant to 1 or
      more of the 12 antimicrobials tested increased by a factor of 1.5, independent of
      antimicrobial treatment. Dogs that were treated with enrofloxacin were 25.6 times
      as likely to be colonized by a quinolone-resistant E coli strain as were dogs
      that did not receive any antimicrobials. Significant correlations were found for
      resistance to agents in the extended-spectrum cephalosporin group and the
      quinolone group. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that the
      proportion of rectal E coli isolates obtained from dogs housed for >or= 3 days in
      a veterinary teaching hospital ICU that were resistant to antimicrobial agents
      increased as the duration of hospitalization in the ICU increased. Thus, ICU
      hospitalization time should be as short as possible to prevent development of
      antimicrobial resistance among rectal E coli isolates.

PMID- 16948578
TI  - Prevalence of DNA of Mycoplasma haemofelis, 'Candidatus Mycoplasma haemominutum,'
      Anaplasma phagocytophilum, and species of Bartonella, Neorickettsia, and
      Ehrlichia in cats used as blood donors in the United States.
AB  - OBJECTIVE: To identify the prevalence of DNA of Mycoplasma haemofelis;
      'Candidatus Mycoplasma haemominutum'; Anaplasma phagocytophilum; and species of
      Bartonella, Neorickettsia, and Ehrlichia in blood of cats used as blood donors in
      the United States. DESIGN: Prospective study. ANIMALS: 146 cats that were active
      blood donors. PROCEDURES: Environmental history was requested for each blood
      donor cat from which a blood sample (mixed with EDTA) was available. Polymerase
      chain reaction assays capable of amplifying the DNA of the microorganisms of
      interest following DNA extraction from blood were performed. RESULTS: Overall,
      DNA of one or more of the infectious agents was detected in blood samples from 16
      of 146 (11%) feline blood donors. Twenty-eight laboratory-reared cats housed in a
      teaching hospital had negative results for DNA of all organisms investigated. The
      DNA of at least 1 infectious agent was amplified from blood samples collected
      from 16 of 118 (13.6%) community-source cats; assay results were positive for
      'Candidatus M haemominutum,' M haemofelis, or Bartonella henselae alone or in
      various combinations. Of the community-source cats allowed outdoors (n = 61) or
      with known flea exposure (44), DNA for a hemoplasma or B henselae was detected in
      21.3% and 22.7%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: When community
      source cats, cats allowed outdoors, or cats exposed to fleas are to be used as
      blood donors, they should be regularly assessed for infection with M haemofelis,
      'Candidatus M haemominutum,' and Bartonella spp, and flea-control treatment
      should be regularly provided.

PMID- 16948580
TI  - Forelimb amputation for treatment of a peripheral nerve sheath tumor in an
      African pygmy hedgehog.
AB  - CASE DESCRIPTION: A 6-year-old female African pygmy hedgehog was evaluated
      because of a mass of unknown duration on the lateral aspect of the right shoulder
      region. CLINICAL FINDINGS: A fine-needle aspirate of the mass was collected for
      cytologic examination; findings were consistent with a spindle cell tumor. A CBC,
      plasma biochemical analyses, and whole-body radiography revealed no other
      abnormalities. TREATMENT AND OUTCOME: An initial surgery performed in an attempt
      to remove the mass with preservation of the limb failed in that tumor-free
      surgical margins were not obtained. Histologically, the mass was identified as a
      peripheral nerve sheath tumor (neurofibrosarcoma). A second surgery to amputate
      the forelimb was successful. After 1 year, there had been no further development
      of peripheral nerve sheath tumor at this or other sites. CLINICAL RELEVANCE: In
      African pygmy hedgehogs, potential differential diagnoses for a subcutaneous mass
      should include peripheral nerve sheath tumor. If necessary, forelimb amputation
      can be performed successfully in this species with procedures modified from those
      used in dogs. Information gathered during the treatment and recovery of the
      hedgehog of this report may assist practicing veterinarians in counseling owners
      of hedgehogs that are undergoing forelimb amputation with regard to the course of
      recovery that may be expected following this procedure.

PMID- 16948582
TI  - Comparison of recoveries from anesthesia of horses placed on a rapidly inflating
      deflating air pillow or the floor of a padded stall.
AB  - OBJECTIVE: To compare recoveries from anesthesia of horses placed on a
      conventional padded stall floor or on a specially designed air pillow. DESIGN:
      Prospective study. ANIMALS: 409 horses (> 1 year old) that were anesthetized for
      surgical procedures during a 37-month period. PROCEDURES: By random allocation,
      horses were allowed to recover from anesthesia in either a foammat-padded
      recovery stall or an identical recovery stall equipped with a rapidly inflating
      deflating air pillow. All recoveries were videotaped for subsequent analysis by
      an independent evaluator. Times to first movement, first attempt to attain
      sternal recumbency, attainment of sternal recumbency, first attempt to stand, and
      successful standing were recorded. The numbers of attempts before achieving
      sternal recumbency and standing were counted, and scores for quality of standing
      and overall recovery were assigned. Recovery-related variables were compared
      between groups. RESULTS: Compared with horses allowed to recover in a
      conventional manner, horses that recovered from anesthesia on the air pillow had
      a significantly longer rest period before attempting to attain sternal recumbency
      and rise to standing. Once the pillow was deflated, horses were able to stand
      after significantly fewer attempts and the quality of their standing was
      significantly better. Between the 2 groups of horses, there was no significant
      difference in overall recovery quality scores. The air pillow and padded floor
      systems were equally safe. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested
      that use of a rapidly inflating-deflating air pillow promotes a longer period of
      recumbency and a better quality of standing after anesthesia in horses.

PMID- 16948584
TI  - Use of magnetic resonance imaging to diagnose distal sesamoid bone injury in a
      horse.
AB  - CASE DESCRIPTION: A 5-year-old Appaloosa mare was examined for severe left
      forelimb lameness of 4 months' duration. CLINICAL FINDINGS: Lameness was evident
      at the walk and trot and was exacerbated when the horse circled to the left.
      Signs of pain were elicited in response to hoof testers placed over the frog of
      the left front hoof, and a palmar digital nerve block eliminated the lameness.
      Radiographs revealed no abnormalities, but magnetic resonance imaging (MRI)
      revealed increased bone density in the medullary cavity of the distal sesamoid
      (navicular) bone in the proton density and T2-weighted images and a defect in the
      fibrocartilage and subchondral bone of the flexor cortex. TREATMENT AND OUTCOME:
      Because of the absence of improvement after 4 months and the poor prognosis for
      return to soundness, the mare was euthanatized. An adhesion between the deep
      digital flexor tendon and the flexor cortex defect on the navicular bone was
      grossly evident, and histologic evaluation revealed diffuse replacement of marrow
      trabecular bone with compact lamellar bone. Changes were consistent with blunt
      traumatic injury to the navicular bone that resulted in bone proliferation in the
      medullary cavity. CLINICAL RELEVANCE: Use of MRI enabled detection of changes
      that were not radiographically evident and enabled accurate diagnosis of the
      cause of lameness. Navicular bone injury may occur without fracture and should be
      considered as a differential diagnosis in horses with an acute onset of severe
      unilateral forelimb lameness originating from the heel portion of the foot.

PMID- 16948585
TI  - Streptococcus equi meningoencephalomyelitis in a foal.
AB  - CASE DESCRIPTION: A 4-month-old American Paint Horse colt was evaluated because
      of acute onset of ataxia, left-sided head tilt, and fever and a recently noticed
      heart murmur. Upper respiratory tract infection caused by Streptococcus equi
      subsp equi had been diagnosed at 3 months of age. CLINICAL FINDINGS: Hematologic
      abnormalities included leukocytosis, mature neutrophilia, monocytosis, and mild
      anemia. Analysis of a CSF sample revealed high total protein concentration and
      total nucleated cell count; nucleated cells consisted mainly of degenerate
      neutrophils. Results of a real-time PCR assay were positive for S equi subsp
      equi, and a diagnosis of S equi subsp equi meningoencephalomyelitis was made.
      TREATMENT AND OUTCOME: Treatment included administration of potassium penicillin
      and fluids, but the foal developed uroperitoneum and was subsequently euthanized.
      Postmortem examination revealed meningoencephalomyelitis, and S equi subsp equi
      was cultured from a brain aspirate. Additional findings included suppurative
      cystitis with rupture and neutrophilic myocarditis. CLINICAL RELEVANCE: Findings
      suggest that S equi subsp equi meningoencephalomyelitis should be considered in
      the differential diagnosis for foals with neurologic signs that have a history of
      strangles or exposure to affected horses.

PMID- 16948586
TI  - Use of transfixation pin casts to treat adult horses with comminuted phalangeal
      fractures: 20 cases (1993-2003).
AB  - OBJECTIVE: To determine the clinical applications, short and long-term survival,
      and complications of using transfixation pin casts for treatment of comminuted
      phalangeal fractures in adult horses. DESIGN: Retrospective case series. ANIMALS:
      20 horses. PROCEDURES: Medical records were reviewed to obtain information
      regarding signalment, fracture location, treatment methods, complications, and
      short-term survival (discharge from hospital). Long-term follow-up information
      was obtained via contact with owners or trainers. RESULTS: 12 fractures were in a
      hind limb, and 8 were in a forelimb. Fourteen fractures occurred in a middle
      phalanx, and 6 occurred in a proximal phalanx. Eleven fractures were treated with
      internal fixation combined with transfixation pin casts, and 9 fractures were
      treated with transfixation pin casts alone. Transfixation pin casts were
      maintained for a mean of 52 days (median, 49 days; range, 1 to 131 days).
      Fourteen (70%) horses were discharged from the hospital, whereas 6 (30%) were
      euthanized during the treatment period. Reasons for euthanasia included secondary
      fracture of the third metacarpal or metatarsal bone, avascularity of the distal
      aspect of the limb associated with an open fracture, and displacement of the
      fracture after transfixation pin cast removal. A significantly greater number of
      horses was discharged from the hospital when the transfixation pin cast was
      maintained for > 40 days, compared with those in which the transfixation pin cast
      was maintained for < 40 days. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      suggested that horses should be maintained in a transfixation pin cast for a
      minimum of 40 days, as this was associated with an increase in short-term
      survival without an increased risk of catastrophic failure.

PMID- 16948588
TI  - Effects of epidural administration of morphine and buprenorphine on the minimum
      alveolar concentration of isoflurane in cats.
AB  - OBJECTIVE: To determine effects of epidural administration of morphine and
      buprenorphine on the minimum alveolar concentration of isoflurane in cats.
      Animals-6 healthy adult domestic shorthair cats. PROCEDURES: Cats were
      anesthetized with isoflurane in oxygen. Morphine (100 microg/kg diluted with
      saline [0.9% NaCl] solution to a volume of 0.3 mL/kg), buprenorphine (12.5
      microg/kg diluted with saline solution to a volume of 0.3 mL/kg), or saline
      solution (0.3 mL/kg) was administered into the epidural space according to a
      Latin square design. The minimum alveolar concentration (MAC) of isoflurane was
      measured in triplicate by use of the tail clamp technique. At least 1 week was
      allowed between successive experiments. RESULTS: The MAC of isoflurane was 2.00
      +/- 0.18%, 2.13 +/- 0.11%, and 2.03 +/- 0.09% in the morphine, buprenorphine, and
      saline solution groups, respectively. No significant difference in MAC was
      detected among treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: A
      significant effect of epidural administration of morphine or buprenorphine on the
      MAC of isoflurane in cats could not be detected. Further studies are needed to
      establish whether epidural opioid administration has other benefits when
      administered as a component of general anesthesia in cats.

PMID- 16948589
TI  - Comparison of high (5%) and low (1%) concentrations of micellar microemulsion
      propofol formulations with a standard (1%) lipid emulsion in horses.
AB  - OBJECTIVE: To compare anesthesia-related events associated with IV administration
      of 2 novel micellar microemulsion preparations (1% and 5%) and a commercially
      available formulation (1%) of propofol in horses. Animals-9 healthy horses.
      PROCEDURES: On 3 occasions, each horse was anesthetized with 1 of the 3 propofol
      formulations (1% or 5% microemulsion or 1% commercial preparation). All horses
      received xylazine (1 mg/kg, IV), and anesthesia was induced with propofol (2
      mg/kg, IV). Induction and recovery events were quantitatively and qualitatively
      assessed. Venous blood samples were obtained before and at intervals following
      anesthesia for quantification of clinicopathologic variables. RESULTS: Compared
      with the commercial formulation, the quality of anesthesia induction in horses
      was slightly better with the micellar microemulsion formulas. In contrast,
      recovery characteristics were qualitatively and quantitatively indistinguishable
      among treatment groups (eg, time to stand after anesthesia was 34.3 +/- 7.3
      minutes, 34.1 +/- 8.8 minutes, and 39.0 +/- 7.6 minutes in horses treated with
      the commercial formulation, 1% microemulsion, and 5% microemulsion,
      respectively). During recovery from anesthesia, all horses stood on the first
      attempt and walked within 5 minutes of standing. No clinically relevant changes
      in hematologic and serum biochemical analytes were detected during a 3-day period
      following anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that
      the micellar microemulsion preparation of propofol (1% or 5%) has similar
      anesthetic effects in horses, compared with the commercially available lipid
      propofol formulation. Additionally, the micellar microemulsion preparation is
      anticipated to have comparatively low production costs and can be manufactured in
      various concentrations.

PMID- 16948590
TI  - Pharmacokinetics and clinical effects of a subanesthetic continuous rate infusion
      of ketamine in awake horses.
AB  - OBJECTIVE: To determine the pharmacokinetics and clinical effects of a
      subanesthetic, continuous rate infusion of ketamine administered to healthy awake
      horses. ANIMALS: 8 adult horses. PROCEDURES: Ketamine hydrochloride was
      administered to 2 horses, in a pilot study, at rates ranging from 0.4 to 1.6
      mg/kg/h for 6 hours to determine an appropriate dose that did not cause adverse
      effects. Ketamine was then administered to 6 horses for a total of 12 hours (3
      horses at 0.4 mg/kg/h for 6 hours followed by 0.8 mg/kg/h for 6 hours and 3
      horses at 0.8 mg/kg/h for 6 hours followed by 0.4 mg/kg/h for 6 hours).
      Concentration of ketamine in plasma, heart rate, respiratory rate, blood
      pressure, physical activity, and analgesia were measured prior to, during, and
      following infusion. Analgesic testing was performed with a modified hoof tester
      applied at a measured force to the withers and radius. RESULTS: No signs of
      excitement and no significant changes in the measured physiologic variables
      during infusion rates of 0.4 and 0.8 mg of ketamine/kg/h were found. At 6 hours
      following infusions, heart rate and mean arterial pressure were decreased,
      compared with preinfusion measurements. An analgesic effect could not be
      demonstrated during or after infusion. Pharmacokinetic variables for 0.4 and 0.8
      mg/kg/h infusions were not significantly different. CONCLUSIONS AND CLINICAL
      RELEVANCE: Ketamine can be administered to awake horses at 0.4 or 0.8 mg/kg/h
      without adverse behavioral effects. The observed pharmacokinetic values are
      different than those reported for single-dose IV bolus administration of this
      drug.

PMID- 16948591
TI  - Effects of increasing infusion rates of dopamine, dobutamine, epinephrine, and
      phenylephrine in healthy anesthetized cats.
AB  - OBJECTIVE: To determine the cardiopulmonary effects of increasing doses of
      dopamine, dobutamine, epinephrine, and phenylephrine and measure plasma
      concentrations of norepinephrine, epinephrine, and dopamine in cats anesthetized
      with isoflurane. ANIMALS: 6 healthy adult cats. PROCEDURES: Each cat was
      anesthetized with isoflurane (1.5 X minimum alveolar concentration) on 4
      occasions. Cardiopulmonary measurements were obtained after a 30-minute
      stabilization period; 20 minutes after the start of each infusion dose; and 30,
      60, and 90 minutes after the infusion was discontinued. Cats received 5
      progressively increasing infusions of epinephrine or phenylephrine (0.125, 0.25,
      0.5, 1, and 2 microg/kg/min) or dobutamine or dopamine (2.5, 5, 10, 15, and 20
      microg/kg/min). The order of treatment was randomly allocated. Results-All 4
      treatments increased oxygen delivery. Heart rate (HR) increased during
      administration of all drugs except phenylephrine, and mean arterial pressure
      increased during administration of all drugs except dobutamine. A progressive
      metabolic acidosis was detected, but whole-blood lactate concentration only
      increased during administration of epinephrine and dobutamine. Systemic vascular
      resistance index increased during administration of phenylephrine, decreased
      during administration of dobutamine, and remained unchanged during administration
      of dopamine and epinephrine. A positive inotropic effect was detected with all
      treatments. CONCLUSIONS AND CLINICAL RELEVANCE: During anesthesia in cats,
      administration of dopamine, dobutamine, and epinephrine may be useful for
      increasing cardiac output, with dopamine having the most useful effects.
      Administration of phenylephrine increased cardiac and systemic vascular
      resistance indexes with minimal effect on HR and may be useful for increasing
      mean arterial pressure without increasing HR.

PMID- 16948592
TI  - Elimination behavior patterns of domestic cats (Felis catus) with and without
      elimination behavior problems.
AB  - OBJECTIVE: To investigate the relationship of litter box location as it relates
      to cats' use of space in the house, elimination problems, and certain behaviors
      associated with elimination. SAMPLE POPULATION: 40 cats in single-cat house-holds
      with or without elimination behavior problems (20 cats/group). PROCEDURES:
      Camcorders were used to record the cats' behaviors at the litter box and other
      areas in which they eliminated during a 72-hour period. Use of space in the house
      was recorded by direct observation during 400 minutes of the 72-hour period.
      Elimination behaviors and other cat- and litter box-associated variables were
      compared between groups; litter box location with respect to inappropriate
      elimination was assessed. RESULTS: Litter box location did not differ between
      cats with and without elimination behavior problems. An inverse correlation was
      found between time spent sniffing and the distance of the litter box from the
      central core area. Cats with elimination problems spent significantly less time
      digging at the litter box than cats without elimination problems. There was no
      significant difference in the time spent pawing in litter box, sniffing, or
      covering excreta after elimination between the 2 groups of cats. CONCLUSIONS AND
      CLINICAL RELEVANCE: Times spent digging in litter boxes by cats with and without
      elimination problems have been determined, and data suggest that actual digging
      times could be used as a means to test for litter preference and litter aversion.
      This information may also be used to identify cats with litter aversion prior to
      the development of an elimination problem.

PMID- 16948593
TI  - Locomotor mechanics of the tolt in Icelandic horses.
AB  - OBJECTIVE: To evaluate the locomotor mechanics of the tolt in Icelandic horses.
      ANIMALS: 10 adult Icelandic horses with no history of lameness. PROCEDURES: Force
      platform data were captured for 27 trials for horses ridden at a tolt in a
      lateral sequence single-foot gait at a steady speed from 0.89 to 5.98 m/s.
      Simultaneous kinematic data were obtained by tracking retroflective markers
      overlying the right fore- and hind limbs. These kinetic and kinematic data were
      combined to evaluate 3 mechanical approaches, duty factor, Froude number, and
      center of mass (COM) mechanics, and to evaluate the capacity to recover
      mechanical energies during tolting via inverse pendulum and spring-mass
      (bouncing) mechanics. RESULTS: Tolting horses had in-phase fluctuations of
      gravitational potential and kinetic energies of their COM and a capacity to
      recover mechanical energy through elastic recoil of spring elements in their
      limbs. These characteristics, along with Froude numbers exceeding values expected
      for the walk-run transition, are indicative of bouncing mechanics and, hence,
      most strongly ally tolting with running. Only the footfall pattern of a lateral
      sequence single-foot gait and low vertical excursions of the COM are more
      commonly associated with walking. CONCLUSIONS AND CLINICAL RELEVANCE: At the
      tolt, horses have unique mechanical characteristics that should be understood for
      veterinary care. Differences in interlimb coordination between tolting and
      trotting mask the overall similarities in most other aspects of their locomotor
      dynamics.

PMID- 16948594
TI  - Development and evaluation of a noninvasive marker cluster technique to assess
      three-dimensional kinematics of the distal portion of the forelimb in horses.
AB  - OBJECTIVE: To develop and evaluate a marker cluster set for measuring sagittal
      and extrasagittal movement of joints in the distal portion of the forelimb in
      ponies. ANIMALS: 4 ponies. PROCEDURES: 5 infrared cameras were positioned on a
      concrete walkway in a frontal-sagittal arc and calibrated. Four segments were
      defined: hoof, middle phalanx, proximal phalanx, and metacarpus. Rigid clusters
      with 4 retroreflective markers were placed on each segment. A static trial was
      recorded with additional anatomic markers on the medial and lateral joint lines.
      Those anatomic markers were removed, and kinematic data were recorded at 240 Hz
      during walking. An ensemble mean was computed from the 4 ponies from 5 replicates
      of the walks. Joint kinematic variables were calculated by use of the calibrated
      anatomical system technique. The design and error dispersion of each marker were
      evaluated. RESULTS: Marker clusters were quasiplanar, but variation in
      orientation error was reduced because the mean radii were > 10 times the largest
      error dispersion values. Measurements of sagittal rotations of the distal
      interphalangeal, proximal interphalangeal, and metacarpophalangeal joints were
      similar to measurements obtained with bone-fixed triads, but larger discrepancies
      between the 2 methods were found for extrasagittal rotations. CONCLUSIONS AND
      CLINICAL RELEVANCE: Development of noninvasive methods for quantifying data
      pertaining to 3-dimensional motion in horses is important for advancement of
      clinical analysis. The technique used in the study enabled identification of
      flexion-extension motions with an acceptable degree of accuracy. Appropriate
      correction algorithms and improvements to the technique may enable future
      quantification of extrasagittal motions.

PMID- 16948595
TI  - Gentamicin concentrations in synovial fluid obtained from the tarsocrural joints
      of horses after implantation of gentamicin-impregnated collagen sponges.
AB  - OBJECTIVE: To determine synovial fluid gentamicin concentrations and evaluate
      adverse effects on the synovial membrane and articular cartilage of tarsocrural
      joints after implantation of a gentamicin-impregnated collagen sponge. ANIMALS: 6
      healthy adult mares. PROCEDURES: A purified bovine type I collagen sponge
      impregnated with 130 mg of gentamicin was implanted in the plantarolateral pouch
      of 1 tarsocrural joint of each horse, with the contralateral joint used as a sham
      operated control joint. Gentamicin concentrations in synovial fluid and serum
      were determined for 120 hours after implantation by use of a fluorescence
      polarization immunoassay. Synovial membrane and cartilage specimens were
      collected 120 hours after implantation and evaluated histologically. RESULTS:
      Median peak synovial fluid gentamicin concentration of 168.9 microg/mL (range,
      115.6 to 332 microg/mL) was achieved 3 hours after implantation. Synovial fluid
      gentamicin concentrations were < 4 microg/mL by 48 hours. Major histologic
      differences were not observed in the synovial membrane between control joints and
      joints implanted with gentamicin-impregnated sponges. Safranin-O fast green stain
      was not reduced in cartilage specimens obtained from treated joints, compared
      with those from control joints. CONCLUSIONS AND CLINICAL RELEVANCE: Implantation
      of a gentamicin-impregnated collagen sponge in the tarsocrural joint of horses
      resulted in rapid release of gentamicin, with peak concentrations > 20 times the
      minimum inhibitory concentration reported for common pathogens that infect
      horses. A rapid decrease in synovial fluid gentamicin concentrations was
      detected. The purified bovine type I collagen sponges did not elicit substantial
      inflammation in the synovial membrane or cause mechanical trauma to the articular
      cartilage.

PMID- 16948596
TI  - Relationship between stages of the estrous cycle and bone cell activity in
      Thoroughbreds.
AB  - OBJECTIVE: To investigate the relationship between stage of estrous cycle and
      bone cell activity in Thoroughbreds. SAMPLE POPULATION: Blood samples collected
      from forty-seven 2-year-old Thoroughbred mares in training for racing.
      PROCEDURES: Blood samples were collected monthly (in April through September)
      from the mares. Stage of estrus was determined by assessing serum progesterone
      concentration. Bone cell activity was determined by measuring concentrations of 2
      markers of bone formation (osteocalcin and the carboxy-terminal propeptide of
      type I collagen [PICP]) and a marker of bone resorption (the cross-linked carboxy
      terminal telopeptide of type I collagen [ICTP]) in sera. RESULTS: When the
      relationship between stage of the estrous cycle and markers of bone cell activity
      was examined, serum concentrations of both osteocalcin and ICTP were
      significantly higher in mares that were in the luteal phase, compared with mares
      that were at other stages of the estrous cycle. Stage of estrus did not affect
      serum PICP concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate
      that bone cell activity in Thoroughbred mares fluctuates during the estrous
      cycle; serum concentrations of markers of bone formation and bone resorption are
      increased during the luteal phase. Further studies are required to determine
      whether these changes are of clinical importance and increase the risk of injury
      for mares in training during the breeding season. As in humans, stage of estrus
      must be considered as a source of uncontrollable variability in serum bone marker
      concentrations in horses.

PMID- 16948597
TI  - Use of a flow-mediated vasodilation technique to assess endothelial function in
      dogs.
AB  - OBJECTIVE: To develop and assess the reproducibility of a protocol to
      noninvasively test endothelial function in dogs on the basis of the flow-mediated
      vasodilation (FMD) procedure used in humans. ANIMALS: 5 healthy spayed female
      dogs. PROCEDURES: Luminal arterial diameter and blood flow velocity in the
      brachial and femoral arteries were measured with ultrasonography. The within-dog
      reproducibility of these ultrasonographic measurements was tested. An occlusion
      period of 1, 3, or 5 minutes with an inflatable cuff was used to create the FMD
      response. Measurements made at 15, 30, and 60 seconds following release of the
      occlusion were compared with measurements made immediately prior to each
      occlusion to assess the FMD response. RESULTS: Within-dog reproducibility of
      measurements revealed moderate to high correlations. Change from baseline in
      luminal arterial diameter was most substantial when measured at 30 seconds
      following release of occlusion, whereas blood flow velocity changes were maximal
      when measured at 15 seconds following release. The brachial imaging site provided
      a larger number of significant FMD responses than the femoral site. The 3-minute
      occlusion period provided equal or better responses than the 5-minute occlusion
      period. CONCLUSIONS AND CLINICAL RELEVANCE: Ultrasonographic measurement of the
      FMD responses was a feasible and reproducible technique and significant changes
      from baseline were detected. The FMD responses in dogs were most substantial when
      performed at the brachial artery with blood flow velocity and luminal arterial
      diameter changes from baseline measured at 15 and 30 seconds, respectively,
      following release of a 3-minute occlusion period.

PMID- 16948598
TI  - Accuracy of an oscillometric blood pressure monitor during phenylephrine-induced
      hypertension in dogs.
AB  - OBJECTIVE: To examine the agreement between direct arterial blood pressure
      measurements obtained from 2 arteries and indirect blood pressure measurements
      obtained with an oscillometric blood pressure monitor (OBPM) during normotension
      and phenylephrine-induced hypertension in dogs. ANIMALS: 16 male Beagles.
      PROCEDURES: In anesthetized dogs, arterial catheters were placed in the lingual
      and dorsal pedal arteries for measurement of arterial blood pressure. A blood
      pressure cuff was placed on either the dog's fore- or hind limb and connected to
      an OBPM. Systolic, diastolic, and mean arterial blood pressures (SAP, DAP, and
      MAP, respectively) were recorded from both arteries and the OBPM every 5 minutes
      for 30 minutes (baseline), during a 30-minute period in which dogs received a
      phenylephrine infusion IV to induce hypertension, and for 30 minutes after
      discontinuation of the infusion. Mean differences in blood pressure values and
      confidence intervals were calculated to compare the indirect and direct
      measurement techniques. RESULTS: In dogs, oscillometry underestimated SAP during
      normotension, and the difference between oscillometric and direct measurements
      increased during hypertension. Oscillometry underestimated DAP, but the
      difference between oscillometric and direct measurements decreased during
      hypertension. There was close agreement among techniques for MAP determinations.
      Biases between direct measurements and OPBM blood pressure values measured from
      dogs' forelimbs or hind limbs were not significantly different. CONCLUSIONS AND
      CLINICAL RELEVANCE: In normotensive dogs, oscillometric measurements of MAP and
      SAP agreed more closely with direct arterial pressure measurements than
      oscillometric estimates of DAP. Oscillometric measurement of MAP was accurate
      during both normotension and hypertension in dogs.

PMID- 16948599
TI  - Comparison of digitized and conventional radiographic images for assessment of
      hip joint conformation in dogs.
AB  - OBJECTIVE: To determine agreement between assessments of canine hip joint
      conformation provided by board-certified radiologists after evaluation of
      digitized and conventional radiographic images. SAMPLE POPULATION: 200 pelvic
      radiographs previously evaluated by radiologists using the Orthopedic Foundation
      for Animals standard grading system for canine hip joint conformation.
      PROCEDURES: Each of 20 board-certified radiologists evaluated conventional and
      digitized pelvic radiographs from each of 200 dogs for hip joint conformation. A
      weighted kappa coefficient and intraclass correlation were used to determine
      agreement between assessments derived from digitized radiographic images and
      conventional radiographs and between the original Orthopedic Foundation for
      Animals conformation ratings and assessments derived from each image format.
      RESULTS: Overall, agreement between assessments derived from the digitized images
      and conventional radiographs was good, with all but 1 radiologist attaining a
      weighted kappa coefficient > 0.61. Intraclass correlation for each radiologist
      ranged from 0.75 to 0.98 (95% confidence interval, 0.67 to 0.984). On comparison
      of conformation assessments, 95.7% of those derived from conventional radiographs
      and digitized images were within 1 grade. On comparison of digitized radiographic
      conformation assessments and conformation ratings, 94.2% were within 1 grade. On
      comparison of conventional radiographic conformation assessments and conformation
      ratings, 92.3% were within 1 grade. CONCLUSIONS AND CLINICAL RELEVANCE: The use
      of digitized radiographic images does not appear to impact the radiographic
      assessments of canine hip joint conformation made by consultant radiologists.
      Compared with conventional radiographs, the use of digitized radiographic images
      decreases storage space requirements and enables more rapid reporting of
      assessment results for individual dogs.

PMID- 16948600
TI  - Effect of adrenalectomy on cholecystokinin-8-induced Fos-like immunoreactivity in
      myenteric neurons and the dorsal vagal complex in rats.
AB  - OBJECTIVE: To investigate the effect of adrenalectomy on cholecystokinin-8 (CCK
      8)-induced Fos-like immunoreactivity (Fos-LI) in the myenteric neurons of the
      dorsal vagal complex (DVC) in rats. ANIMALS: 16 male Sprague Dawley rats.
      PROCEDURES: Rats were allocated to 1 of 2 groups and underwent adrenalectomy or a
      sham adrenalectomy procedure. Rats were challenged with a supraphysiologic dose
      of CCK-8 (40 microg/kg) or physiologic saline (0.9% NaCl) solution (0.5 mL)
      administered IP; after 90 minutes, rats were euthanized, and Fos-LI was
      quantified in the DVC (at the levels of the area postrema, nucleus tractus
      solitarii, and dorsal motor nucleus of the vagus) and the myenteric neurons of
      the duodenum and jejunum by use of a diaminobenzidine reaction enhanced with
      nickel. The Fos-LI-positive cells were counted by use of an automated system and
      manually in the DVC and intestinal samples, respectively. Counts of Fos-LI in the
      different hindbrain levels and myenteric neurons were compared between the
      adrenalectomy--and shamtreated groups and between the CCK-8- and saline solution
      treated groups. RESULTS: After adrenalectomy, CCK-8-induced Fos-LI was attenuated
      only in the myenteric neurons of the duodenum. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results indicate that the adrenal gland has a role in the activation
      of myenteric neurons by CCK-8 in rats.

PMID- 16948601
TI  - Effects of food intake and food withholding on plasma ghrelin concentrations in
      healthy dogs.
AB  - OBJECTIVE: To investigate the physiologic endocrine effects of food intake and
      food withholding via measurement of the circulating concentrations of acylated
      ghrelin, growth hormone (GH), insulin-like growth factor-I (IGF-I), glucose, and
      insulin when food was administered at the usual time, after 1 day's withholding,
      after 3 days' withholding and after refeeding the next day in healthy Beagles.
      ANIMALS: 9 healthy Beagles. PROCEDURES: Blood samples were collected from 8:30 AM
      to 5 PM from Beagles when food was administered as usual at 10 AM, after 1 day's
      withholding, after 3 days' withholding, and after refeeding at 10 AM the next
      day. RESULTS: Overall mean plasma ghrelin concentrations were significantly lower
      when food was administered than after food withholding. Overall mean plasma GH
      and IGF-I concentrations did not differ significantly among the 4 periods.
      Circulating overall mean glucose and insulin concentrations were significantly
      higher after refeeding, compared with the 3 other periods. CONCLUSIONS AND
      CLINICAL RELEVANCE: In dogs, food withholding and food intake were associated
      with higher and lower circulating ghrelin concentrations, respectively,
      suggesting that, in dogs, ghrelin participates in the control of feeding behavior
      and energy homeostasis. Changes in plasma ghrelin concentrations were not
      associated with similar changes in plasma GH concentrations, whereas insulin and
      glucose concentrations appeared to change reciprocally with the ghrelin
      concentrations.

PMID- 16948602
TI  - Evaluation of a covered-rod silicone implant containing ivermectin for long-term
      prevention of heartworm infection in dogs.
AB  - OBJECTIVE: To evaluate use of covered-rod (CR) silicone implants containing
      ivermectin for long-term prevention of infection with Dirofilaria immitisin dogs.
      ANIMALS: 145 adult male and female dogs. PROCEDURES: Dogs received implants of
      different sizes, and ivermectin concentrations and serum ivermectin
      concentrations were monitored for 16, 57, and 56 weeks, respectively, in 3
      preclinical dose selection studies. Ability of implants to prevent infection with
      D immitis was evaluated in 2 further studies; dogs were challenged with 50
      infective third-stage larvae 52 weeks after implant administration and necropsied
      145 days after challenge, and the total number of adult heartworms was counted. A
      field study was then undertaken in which client-owned dogs received an implant
      and plasma samples were collected at intervals until week 52 for ivermectin
      analysis and heartworm antigen determination. RESULTS: Use of the implants
      resulted in maintenance of an ivermectin concentration > or = 0.2 ng/mL for 12
      months. In challenge studies, no treated dogs had adult heartworms, in contrast
      to untreated dogs, which all had adult heartworms at necropsy. In the field
      study, dogs treated with an implant had negative results of heartworm antigen
      testing for 12 months. CONCLUSIONS AND CLINICAL RELEVANCE: The CR silicone
      implant containing 7.3 mg of ivermectin was 100% effective in preventing
      experimental infection with D immitislarvae and resulted in negative results for
      heartworm antigen in a field trial. This product has the potential to alleviate
      poor owner compliance with monthly prevention regimens.

PMID- 16948603
TI  - Clinical, humoral, and pathologic findings in adult alpacas with experimentally
      induced Corynebacterium pseudotuberculosis infection.
AB  - OBJECTIVE: To experimentally infect adult alpacas by ID inoculation of
      Corynebacterium pseudotuberculosis, follow the clinical and pathologic course of
      disease, and study the humoral response to infection. ANIMALS: 13 adult alpacas.
      PROCEDURES: 9 alpacas were inoculated with 1.1 X 10(6) CFUs of C
      pseudotuberculosis from llama (n = 4) or alpaca (5) origin, and 4 alpacas were
      sham inoculated as controls. Alpacas were clinically observed after inoculation
      and euthanatized on days 16, 58, 93, or 128 after inoculation; necropsy
      examination and histologic evaluation were performed. An indirect ELISA, which
      made use of the C pseudotuberculosis cell wall as the antigen, was used to
      measure antibody titers in serum samples. RESULTS: Alpacas had a persistent
      febrile response, a local severe inflammatory response, and leucocytosis (> 30 X
      10(3) WBCs/microL). Internal abscesses that localized mainly in the renal lymph
      node were observed. Corynebacterium pseudotuberculosis was recovered from the
      inoculation site 1 week after inoculation and from internal abscesses at 58 days
      after inoculation. Initial lesions were typical pyogranulomas with central
      caseous necrosis, whereas later lesions consisted of connective tissue,
      mononuclear cells, abundant neutrophils, and liquefactive necrosis. Infected
      alpacas had detectable serum antibody titers starting on day 16 that persisted
      until day 93 after inoculation. Shaminoculated alpacas did not develop serum
      antibody titers, clinical signs of infection, or lesions. CONCLUSIONS AND
      CLINICAL RELEVANCE: Alpacas inoculated with C pseudotuberculosis developed
      abscesses at the inoculation site and internally in the renal lymph nodes,
      without lung lesions. Corynebacterium pseudotuberculosis isolates from llama and
      alpaca origin were found to be pathogenically indistinct.

PMID- 16948604
TI  - Isolation and characterization of a coronavirus from pigeons with pancreatitis.
AB  - OBJECTIVE: To identify and partially characterize a coronaviruslike virus
      isolated from naturally infected pigeons. ANIMALS: 50 specific pathogen-free
      (SPF) embryonated chicken eggs, 30 White Leghorn SPF chickens, and 12 clinically
      normal pigeons. PROCEDURES: Pancreatic tissue specimens from sick pigeons were
      inoculated into SPF embryonated chicken eggs for viral isolation and
      investigation of morphologic and hemagglutinating properties of the isolate,
      called PSH050513. Furthermore, virulence studies in SPF chickens and experimental
      pigeons were performed. The spike (S) glycoprotein gene of PSH050513 was further
      sequenced and analyzed. RESULTS: PSH050513 was isolated and identified from the
      experimentally infected pigeons by a routine method, which was in accordance with
      Koch's postulates. The complete S protein (1,167 amino acids) was compared with
      published S protein sequences of other avian and mammalian coronaviruses. A high
      degree of sequence identity (79.3% to 99.6%) was observed between the S protein
      sequence of PSH050513 and published sequences of avian infectious bronchitis
      virus (IBV); only limited identity (< 37.8%) was observed with turkey coronavirus
      and mammalian coronaviruses. Furthermore, when the virus was inoculated into SPF
      chickens, pancreatitis developed. CONCLUSIONS AND CLINICAL RELEVANCE: PSH050513
      has been tentatively identified as a novel member of group 3 coronaviruses that
      have close genetic relationships with IBV strains.

PMID- 16948605
TI  - Prevalence and antimicrobial resistance patterns of Salmonella enterica in
      preweaned calves from dairies and calf ranches.
AB  - OBJECTIVE: To evaluate serovar and antimicrobial resistance patterns of
      Salmonella enterica isolated from preweaned calves and identify management risk
      factors associated with fecal shedding of S enterica. SAMPLE POPULATION: Cohorts
      of 10 to 15 preweaned calves (1 to 84 days of age) on 26 dairies and 7 calf
      ranches and cross-sectional samples of preweaned calves on smaller farms.
      PROCEDURES: Calves were evaluated every 2 weeks during a 6-week period.
      Salmonella isolates obtained from rectal fecal swabs underwent antimicrobial
      susceptibility testing against 12 antimicrobials. Cluster analysis enabled
      description of antimicrobial susceptibility patterns. Calf, cohort, and farm risk
      factors associated with both the prevalence of S enterica and multiple
      antimicrobial-resistant S enterica in preweaned calves were identified with
      repeated-measure logistic regression models. RESULTS: Salmonella enterica was
      detected on > 50% of farms and in 7.5% of 3,686 fecal samples. Many isolates
      (33%) were resistant to multiple antimicrobials. Shedding of Salmonella spp was
      negatively associated with increasing calf age, herds being closed to incoming
      cattle, and antimicrobial supplementation of milk replacer; prophylactic
      antimicrobial treatment in day-old calves increased shedding. No association
      between farm management and presence of multiple-antimicrobial-resistant S
      enterica or between calving management and presence of S enterica in calves < or
      = 1 week old was detected. CONCLUSIONS AND CLINICAL RELEVANCE: In preweaned
      calves, the most important factors associated with decreased likelihood of fecal
      shedding of S enterica were the use of antimicrobial-supplemented milk replacer
      and maintenance of a closed herd. Infection with multiple-antimicrobial-resistant
      S enterica was not associated with antimicrobial administration.

PMID- 16948606
TI  - Proglycogen, macroglycogen, glucose, and glucose-6-phosphate concentrations in
      skeletal muscles of horses with polysaccharide storage myopathy performing light
      exercise.
AB  - OBJECTIVE: To determine concentrations of proglycogen (PG), macroglycogen (MG),
      glucose, and glucose-6-phosphate (G-6-P) in skeletal muscle of horses with
      polysaccharide storage myopathy (PSSM) before and after performing light
      submaximal exercise. ANIMALS: 6 horses with PSSM and 4 control horses.
      PROCEDURES: Horses with PSSM completed repeated intervals of 2 minutes of walking
      followed by 2 minutes of trotting on a treadmill until muscle cramping developed.
      Four untrained control horses performed a similar exercise test for up to 20
      minutes. Serum creatine kinase (CK) activity was measured before and 4 hours
      after exercise. Concentrations of total glycogen (G(t)), PG, MG, G-6-P, free
      glucose, and lactate were measured in biopsy specimens of gluteal muscle obtained
      before and after exercise. RESULTS: Mean serum CK activity was 26 times higher in
      PSSM horses than in control horses after exercise. Before exercise, muscle
      glycogen concentrations were 1.5, 2.2, and 1.7 times higher for PG, MG, and G(t),
      respectively, in PSSM horses, compared with concentrations in control horses. No
      significant changes in G(t), PG, MG, G-6-P, and lactate concentrations were
      detected after exercise. However, free glucose concentrations in skeletal muscle
      increased significantly in PSSM horses after exercise. CONCLUSIONS AND CLINICAL
      RELEVANCE: Analysis of the results suggests that glucose uptake in skeletal
      muscle is augmented in horses with PSSM after light exercise. There is excessive
      storage of PG and MG in horses with PSSM, and high concentrations of the 2
      glycogen fractions may affect functional interactions between glycogenolytic and
      glycogen synthetic enzymes and glycosomes.

PMID- 16948608
TI  - Effects of platelet-derived growth factor-BB on the metabolic function and
      morphologic features of equine tendon in explant culture.
AB  - OBJECTIVE: To evaluate the effects of recombinant human platelet-derived growth
      factor-BB (rhPDGF-BB) on the metabolic function and morphologic features of
      equine superficial digital flexor tendon (SDFT) in explant culture. Animals-6
      euthanized horses (2 to 5 years old). METHODS: Forelimb SDFT explants were
      cultured for 6 days as untreated control specimens or treated with rhPDGF-BB (1,
      10, 50, or 100 ng/mL of medium). Treatment effects on explant gene expression
      were evaluated via real-time PCR analysis of collagen type I, collagen type III,
      PDGF-A, and PDGF-B mRNA. Explants were assayed for total collagen,
      glycosaminoglycan, and DNA content; histologic changes were assessed via H and E
      staining and immunohistochemical localization of collagen types I and III.
      RESULTS: No morphologic or proliferative changes were detected in tendon explant
      sections. After high-dose rhPDGF-BB treatment, gene expression of collagen types
      I and III was increased and decreased, respectively. Expression of PDGF-A and
      PDGF-B mRNA was significantly increased at 24 hours, but later decreased to have
      few or negative autoinductive effects. Although PDGF gene expression waned after
      48 hours of culture, collagen type I gene expression was significantly increased
      at 48 hours and reached peak value on day 6. Glycosaminoglycan and DNA content of
      explants were unchanged with rhPDGF-BB treatment. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggest that rhPDGF-BB use may be of benefit in the repair of
      equine tendon, particularly through induction of collagen type I mRNA. Positive
      autoinductive effects of PDGF-BB in equine SDFT explants were detected early
      following culture medium supplementation, but these diminished with time.

PMID- 16948609
TI  - Morphologic and morphometric magnetic resonance imaging features of Doberman
      Pinschers with and without clinical signs of cervical spondylomyelopathy.
AB  - OBJECTIVE: To compare morphologic and morphometric features of the cervical
      vertebral column and spinal cord of Doberman Pinschers with and without clinical
      signs of cervical spondylomyelopathy (CSM; wobbler syndrome) detected via
      magnetic resonance imaging (MRI). ANIMALS: 16 clinically normal and 16 CSM
      affected Doberman Pinschers. PROCEDURES: For each dog, MRI of the cervical
      vertebral column (in neutral and traction positions) was performed.
      Morphologically, MRI abnormalities were classified according to a spinal cord
      compression scale. Foraminal stenosis and intervertebral disk degeneration and
      protrusion were also recorded. Morphometric measurements of the vertebral canal
      and spinal cord were obtained in sagittal and transverse MRI planes. RESULTS: 4
      of 16 clinically normal and 15 of 16 CSM-affected dogs had spinal cord
      compression. Twelve clinically normal and all CSM-affected dogs had disk
      degeneration. Foraminal stenosis was detected in 11 clinically normal and 14 CSM
      affected dogs. Vertebral canal and spinal cord areas were consistently smaller in
      CSM-affected dogs, compared with clinically normal dogs. In neutral and traction
      positions, the intervertebral disks of CSM-affected dogs were wider than those of
      clinically normal dogs but the amount of disk distraction was similar between
      groups. CONCLUSIONS AND CLINICAL RELEVANCE: The incidence of intervertebral disk
      degeneration and foraminal stenosis in clinically normal Doberman Pinschers was
      high; cervical spinal cord compression may be present without concurrent clinical
      signs. A combination of static factors (ie, a relatively stenotic vertebral canal
      and wider intervertebral disks) distinguished CSM-affected dogs from clinically
      normal dogs and appears to be a key feature in the pathogenesis of CSM.

PMID- 16948610
TI  - Correlation of motor evoked potentials with magnetic resonance imaging and
      neurologic findings in Doberman Pinschers with and without signs of cervical
      spondylomyelopathy.
AB  - OBJECTIVE: To establish the reference ranges for motor evoked potential (MEP)
      latency and amplitude in clinically normal Doberman Pinschers, compare the MEPs
      of Doberman Pinschers with and without clinical signs of cervical
      spondylomyelopathy (CSM; wobbler syndrome), and determine whether MEP data
      correlate with neurologic or magnetic resonance imaging (MRI) findings. ANIMALS:
      16 clinically normal and 16 CSM-affected Doberman Pinschers. PROCEDURES: Dogs
      were classified according to their neurologic deficits. After sedation with
      acepromazine and hydromorphone, transcranial magnetic MEPs were assessed in each
      dog; latencies and amplitudes were recorded from the extensor carpi radialis and
      cranial tibial muscles. Magnetic resonance imaging was performed to evaluate the
      presence and severity of spinal cord compression. RESULTS: Significant
      differences in cranial tibial muscle MEP latencies and amplitudes were detected
      between clinically normal and CSM-affected dogs. No differences in the extensor
      carpi radialis MEP were detected between groups. There was a significant
      correlation (r = 0.776) between the cranial tibial muscle MEP latencies and
      neurologic findings. Significant correlations were also found between MRI
      findings and the cranial tibial muscle MEP latencies (r = 0.757) and amplitudes
      (r = -0.453). CONCLUSIONS AND CLINICAL RELEVANCE: Results provided a reference
      range for MEPs in clinically normal Doberman Pinschers and indicated that cranial
      tibial muscle MEP latencies correlated well with both MRI and neurologic
      findings. Because of the high correlation between cranial tibial muscle MEP data
      and neurologic and MRI findings, MEP assessment could be considered as a
      screening tool in the management of dogs with spinal cord disease.

PMID- 16948611
TI  - Pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite after oral
      and intravenous administration of pentoxifylline to healthy adult horses.
AB  - OBJECTIVE: To determine serum pharmacokinetics of pentoxifylline and its 5
      hydroxyhexyl metabolite in horses after administration of a single IV dose and
      after single and multiple oral doses. ANIMALS: 8 healthy adult horses.
      PROCEDURES: A crossover study design was used with a washout period of 6 days
      between treatments. Treatments were IV administration of a single dose of
      pentoxifylline (8.5 mg/kg) and oral administration of generic sustained-release
      pentoxifylline (10 mg/kg, q 12 h, for 8 days). Blood samples were collected 0, 1,
      3, 6, 12, 20, 30, and 45 minutes and 1, 2, 4, 6, 8, and 12 hours after IV
      administration. For oral administration, blood samples were collected 0, 0.25,
      0.5, 0.75, 1, 2, 4, 8, and 12 hours after the first dose and 0, 0.25, 0.5, 0.75,
      1, 2, 4, 8, 12, and 24 hours after the last dose. RESULTS: Elimination of
      pentoxifylline was rapid after IV administration. After oral administration,
      pentoxifylline was rapidly absorbed and variably eliminated. Higher serum
      concentrations of pentoxifylline and apparent bioavailability were observed after
      oral administration of the first dose, compared with values after administration
      of the last dose on day 8 of treatment. CONCLUSIONS AND CLINICAL RELEVANCE: In
      horses, oral administration of 10 mg of pentoxifylline/kg results in serum
      concentrations equivalent to those observed for therapeutic doses of
      pentoxifylline in humans. Twice daily administration appears to be appropriate.
      However, serum concentrations of pentoxifylline appear to decrease with repeated
      dosing; thus, practitioners may consider increasing the dosage if clinical
      response diminishes with repeated administration.

PMID- 16948613
TI  - Immunohistochemical staining of urokinase plasminogen activator-like and
      urokinase plasminogen activator receptor-like proteins in the urinary tract of
      healthy dogs.
AB  - OBJECTIVE: To determine distribution of urokinase plasminogen activator-like
      protein and urokinase plasminogen activator receptor-like protein in urinary
      tract tissues of healthy dogs. ANIMALS: 11 healthy dogs. PROCEDURES: Necropsy
      specimens from kidney, ureter, bladder, urethra, prostate, and testis were
      obtained from 4 sexually intact female dogs, 5 sexually intact males, and 2
      castrated males; dogs ranged in age from juvenile to adult. Urokinase plasminogen
      activator-like protein and urokinase plasminogen activator receptor-like protein
      in tissue lysates from kidney, prostate, and testis were identified by use of SDS
      PAGE, western blot analysis, and immunoprecipitation. Urokinase plasminogen
      activator-like protein and urokinase plasminogen activator receptor-like protein
      in kidney, ureter, urinary bladder, urethra, prostate, and testis were identified
      by use of immunohistochemical staining of tissue sections. RESULTS: Urokinase
      plasminogen activator-like protein and urokinase plasminogen activator receptor
      like protein in the molecular-weight range published for urokinase and urokinase
      receptor (53 and 33 kd for urokinase and 60 to 65 kd for urokinase receptor) were
      identified. Distribution of the proteins identified by use of immunohistochemical
      staining was comparable with published information for humans and mice for the
      urinary tract. Staining of these proteins was detected in more tissue types than
      reported in healthy humans. CONCLUSIONS AND CLINICAL RELEVANCE: Urokinase
      plasminogen activator-like protein and urokinase plasminogen activator receptor
      like protein were detected in the urinary tract of healthy dogs. This information
      is important for further evaluation of the functions of urokinase and urokinase
      receptor in the canine urinary tract and the pathophysiologic features of urinary
      tract disease.

PMID- 16948614
TI  - Temporal clinical exacerbation of summer pasture-associated recurrent airway
      obstruction and relationship with climate and aeroallergens in horses.
AB  - OBJECTIVE: To describe the seasonal pattern of clinical exacerbation of summer
      pasture-associated recurrent airway obstruction (SPA-RAO) in relation to climate
      and aeroallergens in horses. ANIMALS: 19 horses with SPA-RAO and 10 nonaffected
      horses. PROCEDURES: Daily examinations were performed on all horses while they
      were kept on pasture for 3 years. Onset and progression of clinical exacerbation
      based on a clinical score of respiratory effort were evaluated in relation to
      changes in maximum temperature, minimum temperature, mean temperature, maximum
      dew-point temperature, minimum dew-point temperature, and delta dew-point
      temperature. Seasonal pattern of clinical exacerbation was evaluated in relation
      to aeroallergen counts (20 types of fungal spores and 28 types of pollen).
      RESULTS: Seasonal pattern of clinical exacerbation of SPA-RAO was associated with
      increases in temperature (heat) and dew-point temperature (humidity), counts of
      fungal spores, and counts of grass pollen grains. Seasonal pattern of clinical
      exacerbation paralleled and was associated with increases in counts of specific
      types of fungal spores, particularly Basidiospore, Nigrospora, and Curvularia
      spp. CONCLUSIONS AND CLINICAL RELEVANCE: Although a causal relationship could not
      be determined, the seasonal pattern of clinical exacerbation of SPA-RAO was
      associated with hot and humid conditions and high environmental counts for fungal
      spores and grass pollen grains. It is not known yet whether these are
      aeroallergens that cause clinical exacerbation of the disease.

PMID- 16948615
TI  - Pharmacogenetics and pharmacogenomics: development, science, and translation.
AB  - Pharmacogenetics and pharmacogenomics involve the study of the role of
      inheritance in individual variation in drug response, a phenotype that varies
      from potentially life-threatening adverse drug reactions to equally serious lack
      of therapeutic efficacy. This discipline evolved from the convergence of rapid
      advances in molecular pharmacology and genomics. Originally, pharmacogenetic
      studies focused on monogenic traits, often involving genetic variation in drug
      metabolism. However, contemporary studies increasingly involve entire "pathways"
      encoding proteins that influence both pharmacokinetics--factors that influence
      the concentration of a drug reaching its target(s)--and pharmacodynamics, the
      drug target itself, as well as genome-wide approaches. Pharmacogenomics is also
      increasingly moving across the "translational interface" into the clinic and is
      being incorporated into the drug development process and the governmental
      regulation of that process. However, significant challenges remain to be overcome
      if pharmacogenetics-pharmacogenomics is to achieve its full potential as a major
      medical application of genomic science.

PMID- 16948616
TI  - Organ donation: a chance for Australia to do better.

PMID- 16948617
TI  - Optimising communication between consumers and clinicians.

PMID- 16948618
TI  - Nutrition surveys or surveillance: one-night stands or a long-term commitment?

PMID- 16948619
TI  - Potential for organ donation in Victoria: an audit of hospital deaths.
AB  - OBJECTIVE: To determine the potential for organ donation in 12 Victorian
      hospitals. DESIGN AND SETTING: Prospective audit of all deaths in 12 major public
      hospitals in the state of Victoria between January 2002 and October 2004. MAIN
      OUTCOME MEASURES: Number of organ donors and potential organ donors (patients
      with brain death or likely to progress to brain death within 24 hours if
      supportive treatment continued), requests for organ donation and consents.
      Unrealised potential donors (organ donation not requested) were categorised by an
      independent panel of intensivists as category A (brain death formally diagnosed);
      B (brain death not formally diagnosed but criteria likely to be fulfilled); and C
      (potential to progress to brain death within 24 hours). RESULTS: There were
      17,230 deaths, 280 potential organ donors and 220 requests for organ donation.
      The 60 unrealised potential organ donors were classified as category A (3), B
      (17) and C (40). Consent rate was 53% to 65%, depending on the definition of
      potential donor (categories A, B and C or category A only). Consent rate was
      lower when discussions about organ donation were held by trainees or registrars
      (21%) than when specialists were present (57%) (P = 0.004). A maximum practically
      achievable organ donation rate for Victoria was estimated to be 15 to 17 donors
      per million population (current rate, 9 per million population). CONCLUSIONS: The
      potential for organ donation in Victoria is limited by a small organ donor pool.
      There is potential to increase the number of organ donors by increasing the
      consent rate (lower than expected from public surveys), the identification of
      potential organ donors (particularly those likely to progress to brain death if
      supportive treatment is continued), and requests for organ donation.

PMID- 16948620
TI  - Risk factors for wound infection after minor surgery in general practice.
AB  - OBJECTIVE: To determine the incidence of and risk factors for surgical site
      infections in general practice. DESIGN: Prospective, observational study of
      patients presenting for minor excisions. SETTING: Primary care in a regional
      centre, Queensland, October 2004 to May 2005. PARTICIPANTS: 857 patients were
      assessed for infection. RESULTS: The overall incidence of infection was 8.6% (95%
      CI, 3.5%-13.8%). Excisions from lower legs and feet (P = 0.009) or thighs (P =
      0.005), excisions of basal cell carcinoma (P = 0.006) or squamous cell carcinoma
      (P = 0.002), and diabetes (P < 0.001) were independent risk factors for wound
      infection. CONCLUSION: Our results indicate the high-risk groups for surgery in a
      general practice setting, such as people with diabetes and those undergoing
      excision of a non-melanocytic skin cancer or excision from a lower limb.
      Recognition of these groups could encourage more judicial use of prophylactic
      antibiotics and use of other interventions aimed at reducing infection rates.

PMID- 16948621
TI  - The assessment of kidney function by general practitioners in Australian patients
      with type 2 diabetes (NEFRON-2).
AB  - OBJECTIVE: To examine factors influencing the identification of kidney impairment
      in patients with type 2 diabetes in Australian primary care. DESIGN, SETTING AND
      PARTICIPANTS: 348 general practitioner investigators were asked to estimate
      kidney function and its severity in 10-15 consecutively presenting patients with
      type 2 diabetes (n = 3893). They were then asked, for each patient, whether they
      routinely estimated kidney function. No instruction was provided on how kidney
      function should be estimated or categorised. Data were collected between April
      and September 2005. MAIN OUTCOME MEASURES: Kidney function estimated by the
      Cockcroft-Gault equation using clinical and laboratory data provided by the GP;
      estimates of kidney function made by the GP. RESULTS: In 24% of the patients with
      type 2 diabetes, their GP routinely estimated kidney function. However, few of
      these patients had impaired kidney function or risk factors for kidney disease.
      There was a good statistical correlation between the estimates made by GPs and
      the data-derived estimates (R2 = 0.72). GPs identified patients with data-derived
      estimates of kidney function < 60 mL/min in over 83% of cases, with a specificity
      of 90%. Impaired kidney function was reported by GPs in 34.4% of men and 36.4% of
      women. These figures were discordant with function categorisation using both GP
      estimates and data-derived values, overlapping in half of the patients. Despite
      GPs' ability to assess creatinine clearance, "raw" (unstandardised) serum
      creatinine levels inappropriately influenced the perception of impairment of
      kidney function. CONCLUSION: GPs can accurately assess kidney function, without
      reporting of estimated glomerular filtration rate (eGFR). However, even in
      patients at increased risk of chronic kidney disease, routine estimates are
      seldom made. Our findings underline the value of the recent initiative
      recommending automatic reporting of eGFR in Australia.

PMID- 16948622
TI  - Does the CONSORT checklist improve the quality of reports of randomised
      controlled trials? A systematic review.
AB  - OBJECTIVE: To determine whether the adoption of the CONSORT checklist is
      associated with improvement in the quality of reporting of randomised controlled
      trials (RCTs). DATA SOURCES: MEDLINE, EMBASE, Cochrane CENTRAL, and reference
      lists of included studies and of experts were searched to identify eligible
      studies published between 1996 and 2005. STUDY SELECTION: Studies were eligible
      if they (a) compared CONSORT-adopting and non-adopting journals after the
      publication of CONSORT, (b) compared CONSORT adopters before and after
      publication of CONSORT, or (c) a combination of (a) and (b). Outcomes examined
      included reports for any of the 22 items on the CONSORT checklist or overall
      trial quality. DATA SYNTHESIS: 1128 studies were retrieved, of which 248 were
      considered possibly relevant. Eight studies were included in the review. CONSORT
      adopters had significantly better reporting of the method of sequence generation
      (risk ratio [RR], 1.67; 95% CI, 1.19-2.33), allocation concealment (RR, 1.66; 95%
      CI, 1.37-2.00) and overall number of CONSORT items than non-adopters
      (standardised mean difference, 0.83; 95% CI, 0.46-1.19). CONSORT adoption had
      less effect on reporting of participant flow (RR, 1.14; 95% CI, 0.89-1.46) and
      blinding of participants (RR, 1.09; 95% CI, 0.84-1.43) or data analysts (RR,
      5.44; 95% CI, 0.73-36.87). In studies examining CONSORT-adopting journals before
      and after the publication of CONSORT, description of the method of sequence
      generation (RR, 2.78; 95% CI, 1.78-4.33), participant flow (RR, 8.06; 95% CI,
      4.10-15.83), and total CONSORT items (standardised mean difference, 3.67 items;
      95% CI, 2.09-5.25) were improved after adoption of CONSORT by the journal.
      CONCLUSIONS: Journal adoption of CONSORT is associated with improved reporting of
      RCTs.

PMID- 16948623
TI  - Prevention and treatment of infant and childhood vitamin D deficiency in
      Australia and New Zealand: a consensus statement.
AB  - Vitamin D deficiency has re-emerged as a significant paediatric health issue,
      with complications including hypocalcaemic seizures, rickets, limb pain and
      fracture. A major risk factor for infants is maternal vitamin D deficiency. For
      older infants and children, risk factors include dark skin colour, cultural
      practices, prolonged breastfeeding, restricted sun exposure and certain medical
      conditions. To prevent vitamin D deficiency in infants, pregnant women,
      especially those who are dark-skinned or veiled, should be screened and treated
      for vitamin D deficiency, and breastfed infants of dark-skinned or veiled women
      should be supplemented with vitamin D for the first 12 months of life. Regular
      sunlight exposure can prevent vitamin D deficiency, but the safe exposure time
      for children is unknown. To prevent vitamin D deficiency, at-risk children should
      receive 400 IU vitamin D daily; if compliance is poor, an annual dose of 150,000
      IU may be considered. Treatment of vitamin D deficiency involves giving
      ergocalciferol or cholecalciferol for 3 months (1000 IU/day if < 1 month of age;
      3000 IU/day if 1-12 months of age; 5000 IU/day if > 12 months of age). High-dose
      bolus therapy (300,000-500,000 IU) should be considered for children over 12
      months of age if compliance or absorption issues are suspected.

PMID- 16948624
TI  - Clinical paradigms revisited.
AB  - Despite astounding advances in scientific knowledge and technological
      capabilities, modern medicine is not free of significant problems. A persistent
      high rate of diagnostic errors, the prevalence of medical (iatrogenic) harm and
      the growing demand for complementary and alternative medicine indicate an urgent
      need for improvement. An important step is a return to three quintessential
      clinical paradigms that have become neglected with the advent of high-technology
      medicine: the need to emphasise prevention and early, presymptomatic diagnosis;
      the crucial role in decision making of skillful history taking and examination,
      backed by evidence; and enhanced attention to patient autonomy and emotional
      factors. Possible reasons for the current neglect of these Altneuparadigms ("old
      new" paradigms) are considered, and techniques for restoring their primacy in
      medicine are discussed.

PMID- 16948625
TI  - The challenge of locum working arrangements in New South Wales public hospitals.
AB  - Use of locum medical officers is increasing in the NSW hospital system. Locums
      are expensive, and have highly variable expertise and experience. Locum
      employment arrangements are ambiguous. Locum work may divert junior doctors from
      participation in specialist training. Attempts to regulate the locum workforce
      must be accompanied by measures that increase the appeal of public hospital work
      and vocational training positions.

PMID- 16948626
TI  - Inhaled corticosteroids, adrenal suppression and benign intracranial
      hypertension.

PMID- 16948627
TI  - A case of human cutaneous anthrax.

PMID- 16948628
TI  - Anaphylaxis: diagnosis and management.
AB  - Anaphylaxis is a serious, rapid-onset, allergic reaction that may cause death.
      Severe anaphylaxis is characterised by life-threatening upper airway obstruction,
      bronchospasm and/or hypotension. Anaphylaxis in children is most often caused by
      food. Bronchospasm is a common symptom, and there is usually a background of
      atopy and asthma. Venom- and drug-induced anaphylaxis are more common in adults,
      in whom hypotension is more likely to occur. Diagnosis can be difficult, with
      skin features being absent in up to 20% of people. Anaphylaxis must be considered
      as a differential diagnosis for any acute-onset respiratory distress,
      bronchospasm, hypotension or cardiac arrest. The cornerstones of initial
      management are putting the patient in the supine position, administering
      intramuscular adrenaline into the lateral thigh, resuscitation with intravenous
      fluid, support of the airway and ventilation, and giving supplementary oxygen. If
      the response to initial management is inadequate, intravenous infusion of
      adrenaline should be commenced. Use of vasopressors should be considered if
      hypotension persists. The patient should be observed for at least 4 hours after
      symptom resolution and referred to an allergist to assist with diagnosis,
      allergen avoidance measures, risk assessment, preparation of an action plan and
      education on the use of self-injectable adrenaline. Provision of a MedicAlert
      bracelet should also be arranged.

PMID- 16948629
TI  - Anaphylaxis to stings and bites.

PMID- 16948631
TI  - Current teaching about obesity in Australian universities, specialist medical
      colleges and through continuing medical education.

PMID- 16948632
TI  - Trans fats in Australian fast foods.

PMID- 16948633
TI  - Guidelines for the management of acute coronary syndromes 2006.

PMID- 16948634
TI  - Evidence into practice: the mental health hurdle is high.

PMID- 16948635
TI  - Interface between residential aged care facilities and a teaching hospital
      emergency department in Western Australia.

PMID- 16948636
TI  - Characterization of A-kinase-anchoring disruptors using a solution-based assay.
AB  - Subcellular localization of PKA (cAMP-dependent protein kinase or protein kinase
      A) is determined by protein-protein interactions between its R (regulatory)
      subunits and AKAPs (A-kinase-anchoring proteins). In the present paper, we report
      the development of the Amplified Luminescent Proximity Homogeneous Assay
      (AlphaScreen) as a means to characterize AKAP-based peptide competitors of PKA
      anchoring. In this assay, the prototypic anchoring disruptor Ht31 efficiently
      competed in RIIalpha isoform binding with RII-specific and dual-specificity AKAPs
      (IC50 values of 1.4+/-0.2 nM and 6+/-1 nM respectively). In contrast, RIalpha
      isoform binding to a dual-specific AKAP was less efficiently competed (IC50 of
      156+/-10 nM). Characterization of two RI-selective anchoring disruptors, RIAD (RI
      anchoring disruptor) and PV-38 revealed that RIAD (IC50 of 13+/-1 nM) was 20-fold
      more potent than PV-38 (IC50 of 304+/-17 nM) and did not compete in the RIIalpha
      AKAP interaction. We also observed that the kinetics of RII displacement from pre
      formed PKA-AKAP complexes and competition of RII-AKAP complex formation by Ht31
      differed by an order of magnitude when the component parts were mixed in vitro.
      No such difference in potency was seen for RIalpha-AKAP complexes. Thus the
      AlphaScreen assay may prove to be a valuable tool for detailed characterization
      of a variety of PKA-AKAP complexes.

PMID- 16948638
TI  - Altered calcium signalling in platelets from bile-duct-ligated rats.
AB  - In the present study, we have analysed the mechanisms of Ca(2+) entry and release
      in platelets obtained from BDL (bile-duct-ligated) rats, 11-13 days and 4 weeks
      after surgery. Platelets were washed and loaded with fura-2, and [Ca(2+)](i)
      (cytosolic Ca(2+) concentration) was determined in cell suspensions by means of
      fluorescence spectroscopy. Basal [Ca(2+)](i) was similar in platelets from BDL
      rats compared with those from their respective controls, both in the absence and
      presence of extracellular Ca(2+). Platelet stimulation with thrombin in the
      absence and presence of extracellular Ca(2+) induced a rapid rise in [Ca(2+)](i)
      that was of greater magnitude in platelets from BDL rats than in controls. Ca(2+)
      storage was significantly elevated in platelets from BDL rats, as well as the
      activity of SERCA (sarcoplasmic/endoplasmic-reticulum Ca(2+)-ATPase).
      Capacitative Ca(2+) entry, as evaluated by inhibition of SERCA with thapsigargin,
      was also altered in platelets from BDL rats, having lower rates of Ca(2+) entry.
      In conclusion, chronic BDL alters intracellular Ca(2+) homoeostasis in platelets,
      such that an enhanced Ca(2+) release is evoked by thrombin, which may be due to
      an increased amount of Ca(2+) stored in the intracellular organelles and
      secondary to an enhanced activity of SERCA. These alterations are already evident
      before cirrhosis has completely developed and occurs during the cholestasis
      phase.

PMID- 16948637
TI  - Accumulation of lipophilic dications by mitochondria and cells.
AB  - Lipophilic monocations can pass through phospholipid bilayers and accumulate in
      negatively-charged compartments such as the mitochondrial matrix, driven by the
      membrane potential. This property is used to visualize mitochondria, to deliver
      therapeutic molecules to mitochondria and to measure the membrane potential. In
      theory, lipophilic dications have a number of advantages over monocations for
      these tasks, as the double charge should lead to a far greater and more selective
      uptake by mitochondria, increasing their therapeutic potential. However, the
      double charge might also limit the movement of lipophilic dications through
      phospholipid bilayers and little is known about their interaction with
      mitochondria. To see whether lipophilic dications could be taken up by
      mitochondria and cells, we made a series of bistriphenylphosphonium cations
      comprising two triphenylphosphonium moieties linked by a 2-, 4-, 5-, 6- or 10
      carbon methylene bridge. The 5-, 6- and 10-carbon dications were taken up by
      energized mitochondria, whereas the 2- and 4-carbon dications were not. The
      accumulation of the dication was greater than that of the monocation
      methyltriphenylphosphonium. However, the uptake of dications was only described
      by the Nernst equation at low levels of accumulation, and beyond a threshold
      membrane potential of 90-100 mV there was negligible increase in dication uptake.
      Interestingly, the 5- and 6-carbon dications were not accumulated by cells, due
      to lack of permeation through the plasma membrane. These findings indicate that
      conjugating compounds to dications offers only a minor increase over monocations
      in delivery to mitochondria. Instead, this suggests that it may be possible to
      form dications within mitochondria that then remain within the cell.

PMID- 16948639
TI  - Inhibition of aggregation in Dictyostelium by EGTA-induced depletion of calcium.
AB  - During aggregation of Dictyostelium discoideum, amoebae move towards collecting
      centres emitting cyclic AMP. Previous work has indicated that Ca2+ can affect the
      operation of various parts of the chemotactic mechanism but there are
      contradictory reports about the role or requirement for Ca2+ during aggregation
      of intact amoebae. In this study we show that there is a requirement for Ca2+
      during this aggregation process. Addition of EGTA (7 mM) and in some cases
      extensive washing with EGTA is needed to see inhibition of aggregation.
      Considerable stores of Ca2+ present within cells may explain the failure of some
      previous attempts to see a Ca2+ requirement during aggregation.

PMID- 16948640
TI  - Mannose-binding lectin in innate immunity: past, present and future.
AB  - The human collectin, mannose-binding lectin (MBL), is an important protein of the
      humoral innate immune system. With multiple carbohydrate-recognition domains, it
      is able to bind to sugar groups displayed on the surfaces of a wide range of
      microorganisms and thereby provide first-line defence. Importantly, it also
      activates the complement system through a distinctive third pathway, independent
      of both antibody and the C1 complex. Three single point mutations in exon 1 of
      the expressed human MBL-2 gene appear to impair the generation of functional
      oligomers. Such deficiencies of functional protein are common in certain
      populations, e.g. in sub-Saharan Africa, but virtually absent in others, e.g.
      indigenous Australians. MBL disease association studies have been a fruitful area
      of research and implicate a role for MBL in infective, inflammatory and
      autoimmune disease processes. Overall, there appears to be a genetic balance in
      which individuals generally benefit from high levels of the protein. However, in
      certain situations, reduced levels of circulating MBL may be beneficial to the
      host and this may explain the persistence of the deleterious gene polymorphisms
      in many population groups.

PMID- 16948641
TI  - Humanized transgenic mice expressing HLA DR4-DQ3 haplotype: reconstitution of
      phenotype and HLA-restricted T-cell responses.
AB  - Many autoimmune conditions have close genetic linkages to particular human
      histocompatibility leukocyte antigen (HLA) class II genes. With the aim of
      establishing a murine model of autoimmune disease, we have generated an HLA DR4
      DQ3 haplotype transgenic (Tg) mouse that expresses a 440-kb yeast artificial
      chromosome harbouring DRA, DRB1*040101, DRB4*010301, DQA1*030101, DQB1*0302 and
      all the internal regulatory segments. This Tg mouse line was crossed to human CD4
      (hCD4) Tg mice and endogenous class II knockout mice (I-A(o/o) and I-E(o/o))
      lines to generate a DR4-DQ3.hCD4.IAE(o/o) Tg line. The Tg DR and DQ molecules are
      expressed on the physiological cell types in these animals, i.e. on most B cells
      (>85%), dendritic cells (DCs) and macrophages but not on T cells, with levels of
      expression comparable with those of human B cells (where DR > DQ expression). The
      DR4/DQ3 transgenes fully reconstituted the CD4 T-cell compartment, in both the
      thymus and the periphery, and the analysis of the T-cell receptor repertoire in
      the Tg mice confirmed that these class II molecules were able to mediate thymic
      selection of a broad range of Vbeta families. HLA DR4- and DQ3-restricted T-cell
      responses were elicited following immunization with known T-cell determinants
      presented by these molecules. Furthermore, the DR4-DQ3-restricted CD4(+) T cells
      conferred protective antibody-mediated immunity against an otherwise lethal
      infection with Salmonella enterica var. typhimurium. These new DR4-DQ3 Tg mice
      should prove to be valuable tools for dissecting the importance of this class II
      haplotype in autoimmune disorders like rheumatoid arthritis.

PMID- 16948642
TI  - Investigation of killer cell immunoglobulin-like receptors gene KIR3DL2 diversity
      and confirmation of KIR3DL2*015 in a Chinese population.
AB  - Human killer cell immunoglobulin-like receptors (KIRs) are a subfamily of the
      immunoglobulin superfamily. Here, we established polymerase chain reaction
      sequence-based typing (PCR-SBT) procedure to identify alleles of KIR3DL2 gene.
      The method was designed around the specific amplification of exon 3 to exon 4 and
      exon 8 to exon 9 of the KIR3DL2 gene. Genomic DNA from 104 healthy, unrelated
      Chinese Han individuals was typed for KIR3DL2 alleles. Each sample was assigned
      to the putative allele combination according to the sequences of all KIR3DL2
      alleles. We observed 18 different genotypes and eight KIR3DL2 alleles in the
      population, with KIR3DL2*002 having the highest frequency of 0.558, and confirmed
      the new KIR3DL2*015 allele. Our data showed that the established PCR-SBT methods
      for KIR3DL2 allele typing were reliable, and Chinese Han population is distinct
      in KIR3DL2 allele frequencies.

PMID- 16948643
TI  - A crypto-Dravidian origin for the nontribal communities of South India based on
      human leukocyte antigen class I diversity.
AB  - The Dravidian communities are considered to be the original inhabitants of India,
      now restricted to South India. The southern most state, Kerala, is socio
      culturally stratified into Hindus, Muslims and Christians on the basis of
      religion. The origin of these religious communities in Kerala is considered to be
      unique in comparison with that in other parts of the country. These communities
      were later influenced by the hierarchical caste structure established by the
      Hindu Brahmins. In the present study, we compared six nontribal (Namboothiri,
      Nair, Ezhava, Pulaya, Malabar Muslim and Syrian Christian) communities belonging
      to the major religious groups in Kerala (Hindu, Muslim and Christian) based on
      the human leukocyte antigen (HLA)-A, -B and -C diversity. Our aim was to
      understand the genomic substructuring associated with the changing social
      scenario in various caste and religious groups and compare it with the Dravidian
      tribal and other world populations. The present study reveals that the HLA
      diversity of the Dravidian communities is very distinct from that in the other
      world populations. It is obvious that the nontribal communities of Kerala display
      a greater Dravidian influence, but traces of genetic admixture with the
      Mediterranean, western European, central Asian and East Asian populations can be
      observed. This characterizes the crypto-Dravidian features of the nontribal
      communities of Kerala. Demic diffusion of the local progressive communities with
      the migrant communities may have given rise to crypto-Dravidian features among
      the nontribal communities of Kerala.

PMID- 16948644
TI  - Development of multiple sclerosis after vaccination against hepatitis B: a study
      based on human leucocyte antigen haplotypes.
AB  - The aetiology of multiple sclerosis (MS) is still not fully understood.
      Infectious agents are believed to play a role in the development of this
      multifactorial disease. Cases in which this disease occurs after administration
      of both plasma-derived and recombinant hepatitis B vaccines have been reported.
      In this study, we compared a group of 11 MS patients who developed first clinical
      symptoms after hepatitis B vaccination (group I) with 71 MS patients who were
      never vaccinated against hepatitis B and were negative for hepatitis B serology
      (group II), and 20 healthy controls (group III). Mean age was 27.75 years (19-39)
      in group I, 30.16 years (18-50) in group II, and 34.4 years (18-50) in group III.
      Mean attack rate after 2 years was 1.5 in group I and 1.63 in group II. Mean
      Expanded Disability Status Scale score after 2 years was 1.31 in group I and 1.89
      in group II. Human leucocyte antigen (HLA) typing and serology for hepatitis B
      surface antigen were performed in all groups. In groups I and II, HLA-DR2 was
      more frequent than in normal healthy subjects. This reflects the general role of
      HLA in the pathogenesis of MS but suggests that antigen presentation by different
      HLA is not involved in the development of MS after hepatitis B vaccination. Since
      there was no difference in the clinical features between vaccinated and
      nonvaccinated MS patients, this study supports recent reports that hepatitis B
      vaccination is safe in MS patients and that hepatitis B vaccination is not
      involved in the development of MS.

PMID- 16948645
TI  - HLA-B35 upregulates the production of endothelin-1 in HLA-transfected cells: a
      possible pathogenetic role in pulmonary hypertension.
AB  - HLA-B35 is associated with an increased risk for developing isolated pulmonary
      hypertension (iPHT) in systemic sclerosis, but the mechanisms underlying this
      association have not been fully elucidated yet. Endothelin-1 (ET-1) is the main
      pathogenetic molecule implied in the development of iPHT; therefore, we sought to
      determine if ECV304 cells transfected with the HLA-B35 allele produce increased
      amounts of ET-1 after incubation with physiological concentrations of interleukin
      1 beta (IL-1beta). ECV304 cells transfected with HLA-B*3501 and HLA-B*0801
      polymorphic alpha chain or with pIRESneo2 were incubated with 100 U/ml of IL
      1beta for 6, 12, 24, 36 and 48 h. ET-1 levels were determined using EIA kit
      (CAYMAN Chemical, Ann Arbor, MI) in supernatants from different cell cultures;
      the relative expression of the preproendothelin-1 (PPET-1) gene was also
      determined by reverse transcription-polymerase chain reaction. Cells expressing
      the HLA-B35 allele showed significantly increased levels of ET-1 at all the
      selected times compared with controls or HLA-B8-transfected cells. The relative
      expression of the PPET-1 gene was also increased in a proportionally direct
      manner. The HLA-B35 allele influences the production of ET-1 in HLA-B35
      transfected ECV304 cells by promoting the expression of its precursor, PPET-1.
      Our results provide an explanation for the epidemiological association existing
      between iPHT and HLA-B35.

PMID- 16948646
TI  - Twenty-three novel HLA-B alleles identified during intermediate-resolution
      testing.
AB  - Twenty-three novel human leukocyte antigen-B alleles are described: B*070204,
      *0738, *0742, *0821, *130202, *1312, *1575, *1598, *1599, *270507, *2728,
      *350104, *3558, *3811, *3931, *3932, *4045, *4107, *420501, *4812, *510106,
      *5520, and *5616. Thirteen of the variants are single-nucleotide substitutions
      from their most homologous allele, eight resulting in amino acid changes (B*0742,
      *1312, *1598, *1599, *3558, *3931, *4107, and *5616) and five with silent
      substitutions (B*070204, *130202, *270507, *350104, and *510106). Three alleles
      (B*0738, *4812, and *5520) differ by five nucleotide changes, altering four amino
      acids. The remaining seven alleles differ from their most similar alleles by two
      to three nucleotides, altering from one to two amino acids.

PMID- 16948647
TI  - Association analysis of MYO9B gene polymorphisms and inflammatory bowel disease
      in a Norwegian cohort.
AB  - Association between single nucleotide polymorphisms (SNPs) within the MYO9B gene
      and celiac disease was recently reported. The role of MYO9B in celiac disease was
      suggested to relate to an epithelial barrier defect. The region to which MYO9B
      localize is also linked with inflammatory bowel disease (IBD). For these reasons,
      we hypothesize that MYO9B could also be a susceptibility gene in IBD. To address
      this, we performed an association study of a Norwegian IBD cohort (149 patients
      with Crohn's disease, 308 patients with ulcerative colitis and 562 healthy
      controls) using SNPs, which tagged the celiac disease associated MYO9B haplotype.
      No association between these SNPs and IBD was observed. Our results failed to
      support the notion that MYO9B is a susceptibility gene in IBD.

PMID- 16948648
TI  - Identification of the new allele B*3556 and extension of the sequences of B*4420
      and B*4427.
AB  - A new B*35 allele, B*3556, was identified in a Caucasian individual. Direct
      sequencing of exons 2 and 3 revealed that B*3556 was identical to B*3503, except
      for a nucleotide substitution from G to A at position 302, which causes a change
      from AGC to AAC at codon 101. This results in an amino acid change from Ser to
      Asn at position 77 of the mature protein. Two B*44 alleles, B*4420 and B*4427,
      were detected in a liver recipient and in an unrelated bone marrow donor,
      respectively, and their sequences were confirmed. The sequences of exons 1,4 and
      5 were also elucidated; for B*4420, these exons proved to be identical to those
      of B*440201. The sequence of exon 5 of B*4427 showed three mismatches with that
      of B*440201, implicating that it probably arose from B*440201 by allele
      conversion with an allele of the B*15, 45, 46, 49 or 50 allele group. Elucidation
      of the sequence of introns 3 and 4 indicated that the breakpoint for allele
      conversion has to be located in intron 3 or exon 4.

PMID- 16948649
TI  - Human leucocyte antigen class II polymorphism in Irish patients with multiple
      sclerosis.
AB  - The contribution of human leucocyte antigen (HLA) to the genetic risk for
      multiple sclerosis (MS) in patients of Northern European Caucasoid ancestry has
      been known since the 1970s. The northern part of Ireland, including county
      Donegal, is known to be a high-risk area for the development of MS. Recorded
      prevalence rates for county Wexford in the south-east Ireland have been markedly
      lower and suggest the existence of a prevalence gradient within the island. To
      evaluate the association of HLA-DRB1 and -DQB1 haplotypes with MS in both Wexford
      and Donegal, we examined a total of 118 patients and 400 regionally matched
      controls. The aim of this exploratory study was to test the possibility of
      heterogeneity in HLA class II associations with MS and to identify potential
      predisposing or protective haplotypes, associated with MS risk in Ireland. We
      confirmed the association of DRB1*1501-DQB1*0602 haplotype carriage with MS in
      both Wexford [odds ratio (OR) = 2.95, P= 0.0020, P(cor)= 0.0220] and Donegal (OR
      = 2.29, P= 0.0030, P(cor)= 0.0420). A higher frequency and a significantly higher
      homozygosity rate of this haplotype in Donegal are likely contributing factors to
      the higher prevalence of MS in Donegal compared with Wexford. The distribution of
      HLA class II alleles among Irish MS patients and controls establishes that there
      is heterogeneity in HLA class II associations with MS within Ireland.

PMID- 16948650
TI  - A*1126: a novel HLA-A11 variant identified by sequence-based typing method.

PMID- 16948651
TI  - A novel human leukocyte antigen-A*01 allele, A*010104, identified by polymerase
      chain reaction-sequence-based typing in a Caucasian hematopoietic stem cell
      donor.

PMID- 16948652
TI  - Identification of a new HLA-A*2464 variant in the Singapore Chinese population.

PMID- 16948653
TI  - Characterization of two new human leukocyte antigen class I alleles B*0829 and
      Cw*0736.

PMID- 16948654
TI  - Characterization of a new HLA-C allele in a Caucasian Italian family by sequence
      based typing: HLA-Cw*0730.

PMID- 16948655
TI  - Nomenclature for factors of the HLA system, update April 2006.

PMID- 16948656
TI  - Nomenclature for factors of the HLA system, update May 2006.

PMID- 16948657
TI  - Nomenclature for factors of the HLA system, update June 2006.

PMID- 16948659
TI  - Mineral trioxide aggregate: a review of the constituents and biological
      properties of the material.
AB  - This paper reviews the literature on the constituents and biocompatibility of
      mineral trioxide aggregate (MTA). A Medline search was conducted. The first
      publication on the material was in November 1993. The Medline search identified
      206 papers published from November 1993 to August 2005. Specific searches on
      constituents and biocompatibility of mineral trioxide aggregate, however, yielded
      few publications. Initially all abstracts were read to identify which fitted one
      of the two categories required for this review, constituents or biocompatibility.
      Based on this assessment and a review of the papers, 13 were included in the
      constituent category and 53 in the biocompatibility category. Relatively few
      articles addressed the constituents of MTA, whilst cytological evaluation was the
      most widely used biocompatibility test.

PMID- 16948660
TI  - Cyclic fatigue resistance and three-dimensional analysis of instruments from two
      nickel-titanium rotary systems.
AB  - AIM: To determine how instrument design affects the fatigue life of two nickel
      titanium (Ni-Ti) rotary systems (Mtwo and ProTaper) under cyclic fatigue stress
      in simulated root canals. METHODOLOGY: Cyclic fatigue testing of instruments was
      performed in stainless steel artificial canals with radii of curvature of 2 or 5
      mm and an angle of curvature of 60 degrees . A total of 260 instruments were
      rotated until fracture occurred and the number of cycles to failure were
      recorded. The morphology of Ni-Ti rotary instruments was investigated by
      measuring the volume of millimetre slices of each instrument size starting from
      the tip to the shank by means of microCT analysis. The fracture surface of three
      representative samples of each size was analysed by scanning electron microscopy
      (SEM). Data were analysed by one-way anova, Holm t-test, paired t-test and linear
      regression; the significance was determined at the 95% confidence level. RESULTS:
      Cycles to failure significantly decreased as the instrument volume increased for
      both the radii of curvature tested (P < 0.01). The radius of curvature had a
      statistically significant influence on the fatigue life of the instruments (P <
      0.05). Larger instruments underwent fracture in less time under cyclic stress
      than smaller ones. SEM evaluation showed typical features of fracture through
      fatigue failure. CONCLUSIONS: The metal volume in the point of maximum stress
      during a cyclic fatigue test could affect the fatigue life of Ni-Ti rotary
      instruments. The larger the metal volume, the lower the fatigue resistance.

PMID- 16948661
TI  - Pulpal anaesthesia for mandibular permanent first molar teeth: a double-blind
      randomized cross-over trial comparing buccal and buccal plus lingual infiltration
      injections in volunteers.
AB  - AIM: To compare the efficacy of buccal and buccal plus lingual infiltration
      anaesthesia for permanent mandibular first molars. METHODOLOGY: Thirty one
      healthy adult volunteers received each of the following methods of anaesthesia
      for a mandibular first molar tooth in a randomised order, 1) Buccal infiltration
      of 1.8 mL and needle penetration lingually. 2) Buccal infiltration of 0.9 mL,
      plus lingual infiltration of 0.9 mL. Two percent lidocaine with 1:100,000
      epinephrine was used. Electrical pulp testing was performed before, and every 2
      minutes for 30 minutes after injection. A successful outcome was recorded as the
      absence of pulp sensation on two or more consecutive maximal pulp tester
      stimulations (80 microA). Injection discomfort was assessed using visual analogue
      scales. Data were compared with McNemar and Wilcoxon Signed Ranks tests. RESULTS:
      Buccal infiltration was successful in 38.7% of cases compared to 32.3% after
      combined infiltrations; the difference was not significant (P = 0.63). Buccal
      infiltration produced more episodes of no response to maximum stimulation than
      buccal and lingual infiltrations (129 and 114 respectively), this difference was
      not significant (P = 0.11). Peak anaesthetic effect occurred around 10-14 minutes
      after injection. There was no difference in injection discomfort between buccal
      injections of 0.9 mL and 1.8 mL of solution (P = 0.90). Lingual injection was
      more uncomfortable than lingual penetration (P = O.O02). CONCLUSIONS: Buccal and
      buccal plus lingual infiltrations did not differ in their efficacy in producing
      anaesthesia of permanent first molar teeth.

PMID- 16948662
TI  - Effect of heat sterilization on surface characteristics and microstructure of
      Mani NRT rotary nickel-titanium instruments.
AB  - AIM: To evaluate the effect of repeated dry heat sterilization on surface
      characteristics and microstructure of Mani nickel-titanium rotary instruments.
      METHODOLOGY: Thirty-three new Mani NRT instruments, size 30, taper 0.04 and 25 mm
      in length were examined. Twenty-seven instruments were divided into three groups
      for surface characterization by scanning electron microscopy (SEM). In the first
      group (n = 3), instruments were examined in the 'as-received' condition and after
      they had been subjected to 11 sterilization cycles. In the second and third
      subgroups (n = 12), 12 instruments were prepared for cross-section and a further
      12 for longitudinal sectional analysis and evaluated in subgroups of three, after
      0, 1, 6 and 11 sterilization cycles. The remaining six instruments were analysed
      with differential scanning calorimetry (DSC), three in the 'as-received'
      condition and three after being subjected to 11 cycles of sterilization. RESULTS:
      Scanning electron microscopy observations indicated the presence of debris,
      pitting and deep milling marks in both new and sterilized files. After 11
      sterilization cycles, debris remained and surface roughness was increased
      significantly (P = 0.05). DSC analyses showed that the specimens in the 'as
      received' condition and after 11 sterilization cycles were in the austenite phase
      or a mixture of austenite and R-phase at 37 degrees C. CONCLUSIONS: The machining
      defects and structural imperfections of new Mani instruments are indicative of
      the difficulty in manufacturing nickel-titanium endodontic instruments. DSC
      measurements suggest that Mani instruments are capable of superelastic behaviour
      under clinical conditions.

PMID- 16948663
TI  - Efficacy of automated versus hand instrumentation during root canal retreatment:
      an ex vivo study.
AB  - AIM: To compare automated and manual instrumentation techniques for removing
      filling material from root canal walls during root canal retreatment.
      METHODOLOGY: One hundred extracted human single-rooted teeth were root filled and
      stored. Specimens were divided into two groups: group A, Endofill plus gutta
      percha; group B, Sealer 26 plus gutta-percha. The filling material was removed
      using the following techniques: group I - Gates-Glidden and K-type files; group
      II - ProFile; group III - ProTaper; group IV - K3; group V- Micro Mega Hero 642.
      The remaining filling debris on the root canal walls were assessed
      radiographically, images were digitized and analysed using Image ProPlus
      software. The roots were split for evaluation in a stereomicroscope by
      epiluminescence and photomicrographs were taken for further analysis. The area
      covered with filling debris was analysed by means of Student's t-test to compare
      the evaluation methods. The student's t-test was also used to compare the removal
      of filling materials. An anova test was applied to compare the different
      techniques (P < 0.05). RESULTS: A significant difference occurred between
      radiographic and photomicrographic evaluation methods (P < 0.05). No significant
      difference was observed between the filling materials on terms of their removal
      (P > 0.05). Manual instrumentation left more filling debris on the root canal
      walls when compared to K3 (P < 0.05) and ProTaper (P < 0.01). CONCLUSIONS: A
      photomicrographic method by epiluminescence was more effective than the
      radiographic method to evaluate filling debris. There was no significant
      difference between the filling materials in terms of their removal. K3 and
      ProTaper were more efficient than manual instrumentation.

PMID- 16948664
TI  - Root canal treatment in Denmark is most often carried out in carious vital molar
      teeth and retreatments are rare.
AB  - AIM: To study the reasons given by a representative sample of Danish general
      dental practitioners (GDPs) for undertaking root canal treatment and, to
      investigate their confidence in performing root canal treatment on molar teeth.
      METHODOLOGY: A questionnaire was sent to 600 Danish GDPs randomly selected from
      the roster of the Danish Dental Association. They were asked to recall various
      factors about their experience of the last root filling they completed, including
      the reason for treatment and the pulp diagnosis. Self-assessments on 100-mm
      visual analogue scales (VAS) were reported concerning the confidence in
      performing root canal treatment of a molar. End-point definitions were 'very
      easy' (0) and 'very difficult' (100), respectively. Time reports of molar
      treatments were given in categorized groups. RESULTS: The most frequent reason
      for performing root canal treatment was caries within the tooth involved (55%).
      The majority of treatments involved teeth with vital pulps (54%). Retreatments
      were carried out in 2% of the cases. The confidence in performing root canal
      treatment varied but was relatively high, expressed as VAS-values below 50. The
      creation of an aseptic working field was regarded as the most difficult procedure
      followed by root canal preparation. Fifty-six percent of the responders stated a
      time frame of 46-75 min to complete root filling in a molar tooth. CONCLUSIONS:
      Root canal treatment in Denmark was reported to be undertaken most often because
      of caries. Treatment was typically performed in molar teeth with vital pulp. Even
      though apical periodontitis was frequently noted in root filled teeth,
      retreatments were rare. From a subjective perspective root canal treatment was
      not considered to be very difficult and was carried out relatively rapidly.

PMID- 16948665
TI  - Shaping ability of progressive versus constant taper instruments in simulated
      root canals.
AB  - AIM: To compare the shaping ability of progressive versus constant taper shaft
      designed instruments in simulated root canals. METHODOLOGY: Simulated L- and S
      shaped resin canals were prepared by ProTaper (progressive taper) and high
      elasticity in rotation 642 (Hero 642) (constant taper) instruments (n = 10 canals
      in each case). The pre- and post-instrumentation images were recorded and
      assessment of the canal shape was completed with image pro plus 5.0. The width of
      resin removed was measured at 9 measuring points. Incidence of canal aberrations,
      instrument fracture, preparation time and change of working length were recorded.
      In addition, the change of curvature and centring ability were also assessed. The
      data were analysed statistically using Student's t-test or Fisher's exact-test.
      RESULTS: In both canal types, Hero 642 instruments prepared canals more rapidly
      (P < 0.01) and maintained working length significantly more accurately than
      ProTaper instruments (P < 0.05). In canals prepared with Hero 642 instruments,
      there was less change in curvature. Instrumentation with ProTaper results in
      transportation towards the outer aspect of the L-shaped curved canals in the
      apical part and the inner aspect of the S-shaped canals at the curve. Hero 642
      instruments had a better centring ability in the apical part of the canal, but
      resulted in shapes with a poor taper. CONCLUSIONS: ProTaper and Hero 642
      instruments prepared curved canals rapidly, maintained working length well and
      were relatively safe without creating perforations and danger zones. In both
      canal types, Hero 642 instruments maintained the original canal curvature better,
      and had a better centring ability in curved canals because of its constant taper
      design. The taper prepared by Hero 642 instruments in the coronal part of the
      canal was generally poor.

PMID- 16948667
TI  - Effects of luting agent and thermocycling on bond strengths to root canal
      dentine.
AB  - AIM: To investigate the effects of luting agent and thermocycling on bond
      strengths to root canal dentine. METHODOLOGY: Extracted maxillary canines (n
      =144) were root filled and divided into six groups of 24 teeth each. Fibre posts
      (FRC Postec) were inserted using six luting agents: Panavia F, Multilink,
      Variolink II, PermaFlo DC, RelyX Unicem and Clearfil Core. Each root was sliced
      into six discs (thickness 1 mm) representing the coronal, middle and apical part
      of the root canal. Push-out tests were performed 24 h after post insertion (n =
      12) as well as after thermocycling (5000x; 5-55 degrees C, 30 s) (n = 12).
      Statistical analysis was conducted using analysis of variance (anova) followed by
      post-hoc comparisons (Tukey-B). The influence of thermocycling on bond strengths
      was investigated for each material and region separately using t-tests. RESULTS:
      The bond strengths were significantly affected by the luting agent (P < 0.001),
      the root position (P = 0.003) and thermocycling (P < 0.001; three-way anova).
      RelyX had significantly higher bond strengths compared with all other materials
      (P < 0.05; Tukey-B). The apical region of the root canal had significantly higher
      bond strengths compared with the middle and coronal region (P < 0.05; Tukey-B).
      After thermocycling for RelyX a significant increase in bond strengths was
      detected for the middle and apical region (P < 0.01; t-test, Bonferroni factor
      18). CONCLUSIONS: Bond strengths were affected significantly by luting agent and
      root position. RelyX had higher bond strengths compared with other materials. The
      apical region of the canals was characterized by significantly higher bond
      strengths.

PMID- 16948666
TI  - Haemostatic agents used in periradicular surgery: an experimental study of their
      efficacy and tissue reactions.
AB  - AIM: To evaluate the haemostatic efficacy and the histologic tissue responses
      after the application of different haemostatic agents used in periradicular
      surgery. METHODOLOGY: The study was conducted in the calvarium of six rabbits.
      Standardized bone defects (diameter 4 mm) were trephined, and different
      haemostatic agents were applied and compared with control defects: bone wax (left
      for 10 min), Stasis (ferric sulphate, left for 5 s), Expasyl (aluminium chloride,
      left for 2 min and left permanently in situ), and a combination of Expasyl (2
      min) and Stasis (5 s). The sites were photographed before the application and
      after the removal of the haemostatic agents. Three independent examiners judged
      the initial and final bleeding (on the photographs) using a bleeding score for
      each site and treatment. The results were compared using Wilcoxon's signed rank
      test. For the histologic analysis, three animals were killed after 3 weeks and
      three animals after 12 weeks. Transverse, nondecalcified sections were stained
      with combined basic fuchsin and toluidine blue for descriptive histology.
      RESULTS: The most efficient haemorrhage control was provided by Expasyl in
      combination with Stasis and by Expasyl alone, whereas bone wax had the weakest
      bleeding reduction effect. The histologic analysis after 3 weeks demonstrated an
      inflammatory and foreign body tissue response towards all haemostatic agents. At
      12 weeks, this tissue response was less pronounced but still present in sites
      treated with bone wax or Expasyl. In general, the inflammatory tissue reactions
      were limited to the bone defects, and never extended into the surrounding
      tissues. CONCLUSIONS: Expasyl alone or in combination with Stasis appeared to be
      the most efficient of tested agents to control the bleeding within the bony
      defects created in a rabbit calvarium model.

PMID- 16948669
TI  - Diagnostic value of computed tomography in re-treatment of root fillings in
      maxillary molars.
AB  - AIM: To compare the diagnostic information and radiation dose between intraoral
      radiography and computed tomography (CT) in re-treatment decision making
      concerning root fillings in maxillary molars. METHODOLOGY: Thirty-nine root
      filled maxillary molars with suspected apical periodontitis were examined with
      two intraoral periapical radiographs and CT. Presence of periapical lesion/s per
      tooth and root were analysed for both techniques. In addition, in the CT images,
      the number of root canals, erosion, or perforation of cortical bone plates, and
      the distance between palatal root and cortical bone plates were evaluated.
      Radiation dose for CT was registered and calculated; and that of periapical
      radiographs used as reported previously (Ekestubbe et al. 2004). RESULTS:
      Periapical radiographs revealed periapical lesions in 33 teeth compared with 38
      on CT images. A lesion of any root was detected more often with CT. The
      mesiobuccal root had two root canals in 30 teeth of which 27 of the MB2 canals
      were not filled, and 22 roots with an unfilled canal were associated a periapical
      lesion. Distances to palatal root, from the buccal and palatal cortex were
      measured in CT and varied between 5.0-12.0 mm and 0-4.0 mm, respectively. Based
      on the radiographic information, a variety of treatment alternatives were
      suggested. Mean effective dose of periapical radiographs was 0.02 mSv and that of
      CT 0.055 mSv. CONCLUSIONS: Computed tomography may give important information in
      re-treatment decision when considering root fillings in maxillary molars. The
      radiation dose should be considered individually.

PMID- 16948668
TI  - Cytokine-induced prostaglandin E2 production and cyclooxygenase-2 expression in
      dental pulp cells: downstream calcium signalling via activation of prostaglandin
      EP receptor.
AB  - AIM: To determine whether (i) proinflammatory cytokines stimulate prostaglandin
      E(2) (PGE(2)) production and cyclooxygenase (COX) gene expression in dental pulp
      cells, and (ii) pulp cells that express different prostaglandin E(2) receptor
      (EP) isoforms and their activation by PGE(2) leads to downstream Ca(2+)
      signalling. METHODOLOGY: Cultured human dental pulp cells were exposed to
      interleukin (IL)-1beta and tumour necrotic factor-alpha (TNF-alpha). The
      expression of COX-1 and COX-2 was measured with reverse transcriptase-polymerase
      chain reaction (RT-PCR). The production of PGE(2) was measured using an enzyme
      linked immunosorbent assay. Expression of prostaglandin EP receptor isoforms was
      studied by RT-PCR, whereas fura-2 fluorescence was used to measure calcium
      mobilization. The Kruskal-Wallis test and Wilcoxon sum rank test with Bonferroni
      correction were used for statistical analysis. RESULTS: Interleukin-1beta and TNF
      alpha stimulate PGE(2) production of human dental pulp cells (P < 0.05). IL-1beta
      stimulated the COX-2 but not COX-1 mRNA expression. Pulp cells express mainly
      EP2, EP3 and EP1 receptors as analysed by RT-PCR. PGE(2) (0.25-2 micromol L(-1))
      stimulated the Ca(2+) mobilization as indicated by increase in fura-2
      fluorescence. CONCLUSIONS: Interleukin-1beta and TNF-alpha may stimulate PGE(2)
      production in dental pulp cells. Activation of prostaglandin EP receptors in
      dental pulp cells by PGE(2) may induce Ca(2+) signalling to regulate cellular
      biological activity during inflammation.

PMID- 16948670
TI  - ESE 12th Biennial Congress, Trinity College, Dublin, 15-17 September 2005 
      'Discover your roots'.

PMID- 16948671
TI  - Retention of resin-based pit and fissure sealants: A systematic review.
AB  - The aim of the present study was to perform a systematic review on the retention
      of resin-based sealants (RBSs) according to the material used and the clinical
      procedure. An electronic search in MEDLINE, EMBASE, Cochrane library and SCOPUS
      was completed by a hand search in conference proceedings. One hundred and twenty
      four studies were identified, 31 of which were included. The retention rate of
      auto-polymerized and light-cured RBSs did not differ significantly. Light-cured
      RBSs had a significantly higher retention rate than fluoride-containing light
      cured RBSs at 48 months (RR = 0.80, 95% CI: 0.72-0.89) and more. Concerning the
      clinical procedure, the scarcity of well-conducted studies made judgement
      difficult, except for the isolation stage. If using a rubber dam did not affect
      retention of auto-polymerized RBSs, it did for fluoride-containing light-cured
      RBSs (RR = 2.03, 95% CI: 1.51-2.73).

PMID- 16948672
TI  - Patient's delay in oral cancer: A systematic review.
AB  - Detecting oral cancer at an early stage is the most effective means of improving
      survival and reducing morbidity from this disease, yet a significant proportion
      of patients delay seeking help after the self-discovery of symptoms of oral
      cancer. The literature on factors associated with patient delay was searched
      systematically to access relevant data published between 1975 and 2005. Eight
      studies met the inclusion criteria for the review. In these studies, most
      clinical/tumour factors, sociodemographic variables, and patient health-related
      behaviours were not related to the duration of patient delay. Healthcare factors
      and psychosocial factors may play a role but the research in this area is sparse,
      atheoretical and of poor quality. Patient delay is a problem in oral cancer and
      yet at present the reasons for such delays are poorly understood and under
      researched. Systematic, high-quality and theory-driven research in this area is
      urgently required.

PMID- 16948673
TI  - The potential impact of neighborhood empowerment on dental caries among
      adolescents.
AB  - OBJECTIVE: Empowerment has been considered a dimension of social capital. It
      refers to social interaction processes that enable people to enhance their
      individual and collective skills and to exert greater control over their lives.
      This relationship has not been explored in relation to dental health. The
      objective of this study was to investigate the association between neighborhood
      empowerment and dental caries in adolescents. METHODS: A multilevel study was
      designed to assess the individual and neighborhood effects on the oral health of
      adolescents. Four sources of data were used: (a) clinical examinations (WHO), (b)
      students' questionnaires, (c) parents' questionnaires and (d) census data. The
      study population was 1302, 14/15-year-old students from 39 public schools of two
      cities of the Distrito Federal (DF), Brazil. Data analysis used logistic
      multilevel modeling at two levels: students (sources a and b) and neighborhood as
      defined by catchment areas of schools (sources c and d). RESULTS: High DMFT (DMFT
      > median, DMFT > or =3) rates were significantly lower in areas with higher
      levels of empowerment. This relationship was independent of socioeconomic
      variables at the individual and area levels and of all other individual risk
      factor variables such as sex, fluoride, sugar consumption, tooth brushing and
      dental attendance [OR for low compared with high empowerment was 1.54 (95% CI =
      1.09-2.18), P = 0.014]. CONCLUSIONS: Neighborhood empowerment may play an
      important role in explaining inequalities in the levels of dental caries. New
      perspectives are needed so that more effective interventions can be implemented
      using area-based perspectives.

PMID- 16948674
TI  - Utility of two oral health-related quality-of-life measures in patients with
      xerostomia.
AB  - OBJECTIVES: The study compared the validity of the short form of the Oral Health
      Impact Profile (OHIP) and Oral Impacts on Daily Performance (OIDP) as measures of
      oral health-related quality of life in patients with xerostomia in the UK.
      METHODS: A cross-sectional comparison of OHIP14 and OIDP with measures of
      clinical indicators, xerostomia symptom status, speech function, global oral
      health ratings and psychological well-being, in 85 patients attending outpatient
      clinics. RESULTS: Both OHIP14 and OIDP had excellent internal reliability, and
      good criterion and construct validity when used in this population of xerostomia
      patients. In regression analyses, salivary gland condition and xerostomia symptom
      status significantly predicted oral health-related quality of life (OHRQoL),
      accounting for 29% and 14% of the variance in OHIP and OIDP scores respectively.
      In turn, OHRQoL predicted global ratings of oral health (26% of variance) and
      psychological well-being (depression) scores (15%). Sex, ethnicity and age were
      associated with clinical presentation and patient-reported symptoms. Clinical
      presentation, OHRQoL (as measured by the OIDP) and speech function were related
      to duration of symptoms. CONCLUSION: Both OHIP14 and OIDP have good psychometric
      properties and appear useful measures of OHRQoL in xerostomia. Overall, the
      OHIP14 performed better than did OIDP. For both measures, the additive scoring
      method may be more relevant for this population that the number of impacts.

PMID- 16948675
TI  - Dental status and measures of deprivation in Clermont-Ferrand, France.
AB  - BACKGROUND: Many background variables, such as socioeconomic status (SES), may be
      measured at the level of the individual or using some ecological indicators.
      OBJECTIVES: This study aimed to examine, in 5- and 10-year-olds in Clermont
      Ferrand, the relationship between household SES indicators, SES measured as an
      area-based ecological variable and dental status. METHODS: All 5- and 10-year
      olds attending public schools in deprived and semi-deprived zones (n = 15) and
      six other randomly selected schools in Clermont-Ferrand were invited to
      participate. All children were examined clinically. On a questionnaire, parents
      provided sociodemographic information. RESULTS: Of the children invited, 84% (880
      children) were examined. Mean dft of 5-year-olds was 0.93 (SD 2.27); 26.5% had at
      least one tooth affected. The caries experience (DMFT) of 10-year-olds was 0.85
      (SD 1.14) and 37.2% had permanent tooth caries experience. Caries experience
      varied significantly with school deprivation status: the greater the deprivation
      score, the more likely was poor dental health. Country of birth, parents'
      employment status, family size and health insurance type were significantly
      related to dental status. Logistic analyses estimated the importance of SES and
      ecological variables; deprivation influenced dental status in 5-year-olds even
      when household SES indicators were considered. In 10-year-olds, caries experience
      was influenced by household SES, immigrant background, father's employment and
      family size. CONCLUSION: The use of school deprivation as an ecological measure
      status was useful for identifying population subgroups with different levels of
      oral health, particularly in young children. This indicator of social deprivation
      could be used for targeting preventive programmes to high caries risk communities
      defined geographically.

PMID- 16948676
TI  - Sugar snack consumption in Ugandan schoolchildren: Validity and reliability of a
      food frequency questionnaire.
AB  - OBJECTIVES: This study assessed the reproducibility and relative validity of an
      eight-item self-administered food frequency questionnaire (FFQ) on intake of
      sugared snacks in Ugandan schoolchildren. A 5-day precoded food behaviour
      checklist (FBC) was used as validation criteria. Sociodemographic correlates of a
      sum frequency sugar score were explored. METHODS: The study was conducted in
      Kampala, Uganda, in 2004. Six hundred and fourteen schoolchildren (mean age 12.4
      years) completed the FFQ on cakes/biscuits, chocolate, ice sticks, soft drinks,
      coffee, tea, sugared desserts and sweets/candies at school. They were examined
      clinically for dental caries. Forty students completed the FFQ twice, 1 week
      apart and 325 students completed the 5 day FBC at school. RESULTS: The mean
      decayed, missing and filled tooth index score was 0.98 (SD 1.6, range 0-15).
      Reproducibility scores (Cohen's kappa) for the sugar items ranged from 0.17 (ice
      sticks) to 0.55 (biscuits). No differences were seen between the average intakes
      at test and retest. Higher intake was reported in FFQ than in FBC across all
      sugar items. Crude agreement between students reporting intake at least 3-5 times
      a week/less than three times a week ranged from 50% to 55% (e.g. biscuits,
      chocolate) to 87% (tea). Spearman's correlation coefficients ranged from 0.14
      (desserts) to 0.27 (sweets). anova revealed significant increase (P = 0.001) in
      the mean FBC sum scores by increasing quartiles of the FFQ sum scores. The
      average sum FFQ sugar scores were higher in girls than in boys and higher in
      older than in younger students. CONCLUSION: Fair reproducibility was established
      for the FFQ sugar items. The FFQ was acceptable in classifying individuals into
      broad categories of low and high sugar consumption.

PMID- 16948677
TI  - Outcomes associated with dentists' risk assessment.
AB  - OBJECTIVE: To examine retrospectively the caries-related restorative experience
      of at-risk individuals who received fluoride-based preventive interventions to
      determine if the intervention resulted in fewer caries-related procedures.
      METHODS: Administrative data from two dental health plans were used to determine
      the relationship between caries risk assessment (CRA) scores, preventive
      treatment and caries-related treatment procedures. We identified 45 693 adults
      who were consecutively enrolled for at least 1 year before and 2.5 years after
      the CRA. Variables representing the number of teeth with any caries-related
      treatment procedure and receipt of preventive treatment were created. RESULTS:
      The outcome variable of interest was having at least one tooth with a caries
      related procedure in the 2-year follow-up period. In plan A, the recommendation
      for home-use fluoride was not significantly related to caries-related treatment
      procedures in the follow-up period for individuals at low, moderate or high risk
      (P > 0.300). In plan B, application of in-office fluoride was associated with
      having at least one tooth with a caries-related treatment procedure in the follow
      up period (P < 0.001). CONCLUSIONS: We found incomplete compliance with
      guidelines for recommendation or administration of preventive treatment for
      patients at elevated risk for caries. We were also unable to identify any
      significant reductions in caries-related procedures for individuals receiving a
      fluoride intervention, compared with those who did not, when stratified by risk
      level.

PMID- 16948678
TI  - Factors associated with dental health care coverage in Mexico: Findings from the
      National Performance Evaluation Survey 2002-2003.
AB  - OBJECTIVES: To determine the level of dental health care coverage in people aged
      > or =18 years across the country, and to identify the factors associated with
      coverage. MATERIAL AND METHODS: Using the instruments and sampling strategies
      developed by the World Health Organization for the World Health Survey, a cross
      sectional national survey was carried out at the household and individual (adult)
      levels. Dental data were collected in 20 of Mexico's 32 states. The relationship
      between coverage and environmental and individual characteristics was examined
      through logistic regression models. RESULTS: Only 6098 of 24 159 individual
      respondents reported having oral problems during the preceding 12 months
      (accounting for 14 284 621 inhabitants of the country if weighted). Only 48% of
      respondents reporting problems were covered, although details of the
      appropriateness, timeliness and effectiveness of the intervention(s) were not
      assessed. The multivariate regression model showed that higher level of
      education, better socioeconomic status, having at least one chronic disease and
      having medical insurance were positively associated with better dental care
      coverage. Age and sex were also associated. CONCLUSIONS: Overall dental health
      care coverage could be improved, assuming that ideal coverage is 100%. Some
      equality of access issues are apparent because there are differences in coverage
      across populations in terms of wealth and social status. Identifying the factors
      associated with sparse coverage is a step in the right direction allowing
      policymakers to establish strategies aimed at increasing this coverage, focusing
      on more vulnerable groups and on individuals in greater need of preventive and
      rehabilitative interventions.

PMID- 16948680
TI  - Daily soil ingestion estimates for children at a Superfund site.

PMID- 16948682
TI  - Within-animal variation as an indication of the minimal magnitude of the critical
      effect size for continuous toxicological parameters applicable in the benchmark
      dose approach.
AB  - In this study, the within-animal variation in routinely studied continuous
      toxicological parameters was estimated from temporal fluctuations in individual
      healthy nonexposed animals. Assuming that these fluctuations are nonadverse, this
      within-animal variation may be indicative of the minimal magnitude of the
      critical effect size (CES). The CES is defined as the breaking point between
      adverse and nonadverse changes in a continuous toxicological parameter, at the
      level of the individual organism. The total variation in the data from individual
      nonexposed animals was divided in variation parts due to known factors
      (differences in sex, animal, and day) and a residual variation, by means of
      analysis of variance. Using the residual variation and the estimated analytical
      measurement error of a toxicological parameter, the within-animal variation can
      be estimated. The data showed within-animal variations ranging between 0.6% and
      34% for different clinical chemistry and hematological parameters in 90-day rat
      studies. This indicates that different (minimal) CES values may be applicable for
      different parameters.

PMID- 16948683
TI  - Estimating preventable fractions of disease caused by a specified biological
      mechanism: PAHs in smoking lung cancers as an example.
AB  - Epidemiology textbooks often interpret population attributable fractions based on
      2 x 2 tables or logistic regression models of exposure-response associations as
      preventable fractions, i.e., as fractions of illnesses in a population that would
      be prevented if exposure were removed. In general, this causal interpretation is
      not correct, since statistical association need not indicate causation; moreover,
      it does not identify how much risk would be prevented by removing specific
      constituents of complex exposures. This article introduces and illustrates an
      approach to calculating useful bounds on preventable fractions, having valid
      causal interpretations, from the types of partial but useful molecular
      epidemiological and biological information often available in practice. The
      method applies probabilistic risk assessment concepts from systems reliability
      analysis, together with bounding constraints for the relationship between event
      probabilities and causation (such as that the probability that exposure X causes
      response Y cannot exceed the probability that exposure X precedes response Y, or
      the probability that both X and Y occur) to bound the contribution to causation
      from specific causal pathways. We illustrate the approach by estimating an upper
      bound on the contribution to lung cancer risk made by a specific, much-discussed
      causal pathway that links smoking to a polycyclic aromatic hydrocarbon (PAH)
      (specifically, benzo(a)pyrene diol epoxide-DNA) adducts at hot spot codons at p53
      in lung cells. The result is a surprisingly small preventable fraction (of
      perhaps 7% or less) for this pathway, suggesting that it will be important to
      consider other mechanisms and non-PAH constituents of tobacco smoke in designing
      less risky tobacco-based products.

PMID- 16948684
TI  - Environmental surveillance at Los Alamos: an independent reassessment of
      historical data.
AB  - Since 1971, a series of annual Environmental Surveillance ... reports have served
      as the official public record of Los Alamos National Laboratory's (LANL)
      environmental performance. In northern New Mexico, where past LANL emissions are
      a public health concern, there is public skepticism over the accuracy of
      information contained in these reports. To test the hypothesis that LANL
      Environmental Surveillance ... reports systematically understate past emissions,
      we compared the data on releases in LANL's own internal Occurrence Reports
      Collection (ORC) to the data reported to the public in the Environmental
      Surveillance ... reports. A data set of 89 environmental occurrences recorded in
      the ORC in the time period from 1971 through 1980 was assembled. We did not find
      a systematic pattern of quantitative underreporting of source terms. However, 17
      of the 89 (19%) environmental occurrences recorded in the ORC were not reported
      to the public in the Environmental Surveillance ... reports. The observed
      discrepancies are discussed in terms of their relevance to public health
      concerns. Methodological caveats dictate restraint in applying these findings
      beyond the scope of the relative comparison performed here. Possible social
      origins for the rejected hypothesis are discussed. Areas for further
      consideration by the Centers for Disease Control's dose reconstruction study of
      LANL are identified.

PMID- 16948685
TI  - A macro-economic framework for evaluation of cyber security risks related to
      protection of intellectual property.
AB  - The article is based on the premise that, from a macro-economic viewpoint, cyber
      attacks with long-lasting effects are the most economically significant, and as a
      result require more attention than attacks with short-lasting effects that have
      historically been more represented in literature. In particular, the article
      deals with evaluation of cyber security risks related to one type of attack with
      long-lasting effects, namely, theft of intellectual property (IP) by foreign
      perpetrators. An International Consequence Analysis Framework is presented to
      determine (1) the potential macro-economic consequences of cyber attacks that
      result in stolen IP from companies in the United States, and (2) the likely
      sources of such attacks. The framework presented focuses on IP theft that enables
      foreign companies to make economic gains that would have otherwise benefited the
      U.S. economy. Initial results are presented.

PMID- 16948686
TI  - Physiologically-based pharmacokinetic modeling of benzene in humans: a Bayesian
      approach.
AB  - Benzene is myelotoxic and leukemogenic in humans exposed at high doses (>1 ppm,
      more definitely above 10 ppm) for extended periods. However, leukemia risks at
      lower exposures are uncertain. Benzene occurs widely in the work environment and
      also indoor air, but mostly below 1 ppm, so assessing the leukemia risks at these
      low concentrations is important. Here, we describe a human physiologically-based
      pharmacokinetic (PBPK) model that quantifies tissue doses of benzene and its key
      metabolites, benzene oxide, phenol, and hydroquinone after inhalation and oral
      exposures. The model was integrated into a statistical framework that
      acknowledges sources of variation due to inherent intra- and interindividual
      variation, measurement error, and other data collection issues. A primary
      contribution of this work is the estimation of population distributions of key
      PBPK model parameters. We hypothesized that observed interindividual variability
      in the dosimetry of benzene and its metabolites resulted primarily from known or
      estimated variability in key metabolic parameters and that a statistical PBPK
      model that explicitly included variability in only those metabolic parameters
      would sufficiently describe the observed variability. We then identified
      parameter distributions for the PBPK model to characterize observed variability
      through the use of Markov chain Monte Carlo analysis applied to two data sets.
      The identified parameter distributions described most of the observed
      variability, but variability in physiological parameters such as organ weights
      may also be helpful to faithfully predict the observed human-population
      variability in benzene dosimetry.

PMID- 16948687
TI  - Direct estimation of the cost effectiveness of tornado shelters.
AB  - This article estimates the cost effectiveness of tornado shelters using the
      annual probability of a tornado and new data on fatalities per building struck by
      a tornado. This approach differs from recent estimates of the cost effectiveness
      of tornado shelters in Reference 1 that use historical casualties. Historical
      casualties combine both tornado risk and resident action. If residents of tornado
      prone states take greater precautions, observed fatalities might not be much
      higher than in states with lower risk. Estimation using the tornado probability
      avoids this potential bias. Despite the very different method used, the estimates
      are 68 million US dollars in permanent homes and 6.0 million US dollars in mobile
      homes in Oklahoma using a 3% real discount rate, within about 10% of estimates
      based on historical fatalities. The findings suggest that shelters provide cost
      effective protection for mobile homes in the most tornado-prone states but not
      for permanent homes.

PMID- 16948688
TI  - Using graph models to analyze the vulnerability of electric power networks.
AB  - In this article, we model electric power delivery networks as graphs, and conduct
      studies of two power transmission grids, i.e., the Nordic and the western states
      (U.S.) transmission grid. We calculate values of topological (structural)
      characteristics of the networks and compare their error and attack tolerance
      (structural vulnerability), i.e., their performance when vertices are removed,
      with two frequently used theoretical reference networks (the Erdos-Renyi random
      graph and the Barabasi-Albert scale-free network). Further, we perform a
      structural vulnerability analysis of a fictitious electric power network with
      simple structure. In this analysis, different strategies to decrease the
      vulnerability of the system are evaluated. Finally, we present a discussion on
      the practical applicability of graph modeling.

PMID- 16948689
TI  - Flooding risks: a comparison of lay people's perceptions and expert's assessments
      in Switzerland.
AB  - Experts on the risk of flooding have developed very detailed maps for different
      parts of Switzerland that indicate the types of damage possible and the
      probabilities of adverse events. Four categories of risk severity are defined on
      the maps, ranging from high risk to no risk. Based on these existing maps, we
      selected respondents for a mail survey, some from areas high in risk and others
      from low-risk regions. Respondents answered several questions related to flood
      risk perception and preparedness. Survey results showed that respondents' risk
      perceptions were correlated with the experts' risk assessments. Respondents who
      lived in areas designated "no risk" by the experts had lower perceptions of risk
      than respondents who lived in areas with higher levels of designated risk. With
      regard to concrete prevention behavior, no differences between people living in
      different risk areas were observed. Survey results further suggest that many
      inhabitants do not know that flooding maps exist for their region. Results
      suggest that in some regions people overestimate the risks associated with
      flooding. Consequently, some people are more afraid of flooding than is justified
      by the facts. Some people show prevention behavior that most likely is
      superfluous. However, in other regions people underestimate the risks associated
      with flooding. These people do not show prevention behavior, and they are not
      well prepared for an adverse event. Furthermore, results suggest that
      respondents' experiences with flooding are positively related to their
      perceptions of flood risk. Findings of the present study are in line with the
      availability heuristic.

PMID- 16948690
TI  - Application of the precautionary principle by senior policy officials: results of
      a Canadian survey.
AB  - Though use of the controversial precautionary principle in risk management has
      increasingly been recommended as a guide for the construction of public policy in
      Canada and elsewhere, there are few data available characterizing its use in risk
      management by senior public policymakers. Using established survey methodology we
      sought to investigate the perceptions and terms of application of the
      precautionary principle in this important subset of individuals. A total of 240
      surveys were sent out to seven departments or agencies in the Canadian
      government. The overall survey response rate was 26.6%, and our findings need to
      be interpreted in the context of possible responder bias. Of respondents, the
      overwhelming majority perceived the precautionary principle and the management of
      risk as complementary, and endorsed a role for the precautionary principle as a
      general guideline for all risk management decisions. However, 25% of respondents
      responded that the lack of clarity of the definition of the principle was a
      limitation to its effective use. The majority of respondents viewed their own
      level of understanding of the precautionary principle as moderate. Risk managers
      appeared to favor an interpretation of the precautionary principle that was based
      on the seriousness and irreversibility of the threat of damage, and did not
      endorse as strongly the need for cost effectiveness in the measures taken as a
      precaution against such threats. In contrast with its perceived role as a general
      guideline, the application of the precautionary principle by respondents was
      highly variable, with >60% of respondents reporting using the precautionary
      principle in one-quarter or less of all risk management decisions. Several
      factors influenced whether the precautionary principle was applied with the
      perceived seriousness of the threat being considered the most influential factor.
      The overwhelming majority of risk managers felt that "preponderance of evidence"
      was the level of evidence required for precautionary action to be instituted
      against a serious negative event. Overall, the majority of respondents viewed the
      precautionary principle as having a significant and positive impact on risk
      management decisions. Importantly, respondents endorsed a net result of more good
      than harm to society when the precautionary principle was applied to the
      management of risk.

PMID- 16948691
TI  - Egyptian farmers' attitudes and behaviors regarding agricultural pesticides:
      implications for pesticide risk communication.
AB  - The need to boost pre- and postharvest agricultural productivity serves as a
      powerful driving force for developing countries to promote the use of
      agricultural pesticides. Pesticides are, however, "poisons by design" and
      poisonings resulting from unsafe use of these chemicals are the most prevalent
      and serious occupational hazards faced by agricultural workers in developing
      countries. This article provides the results of a study designed to investigate
      the extent of unsafe use of pesticides by farmers in one of the largest
      agricultural areas in Egypt, the farmers' knowledge about pesticides, and their
      preferred sources of receiving risk information on pesticides. The results of
      this study show a high level of unsafe use of pesticides and inappropriate
      methods of disposal of empty pesticide containers. Also, knowledge about
      pesticides is scant. Notwithstanding that more than half of the farmers obtain
      regular drinking water from wells, most of the respondents were "not sure" as to
      whether or not pesticides may contaminate groundwater. The low level of knowledge
      about pesticides can be attributed to relatively low levels of education and that
      almost all the respondents have never participated in a pesticide education
      program. This article concludes with a recommendation for pesticide and pesticide
      use education programs, especially through "ministry officials" who most of the
      respondents seem to trust regarding receiving pesticide information.

PMID- 16948692
TI  - Integrating software into PRA: a software-related failure mode taxonomy.
AB  - Probabilistic risk assessment is a methodology to assess the probability of
      failure or success of a mission. Results provided by the risk assessment
      methodology are used to make decisions concerning choice of upgrades, scheduling
      of maintenance, decision to launch, etc. However, current PRA neglects the
      contribution of software to the risk of failure of the mission. Our research has
      developed a methodology to account for the impact of software to system failure.
      This article focuses on an element of the approach: a comprehensive taxonomy of
      software-related failure modes. Application of the taxonomy is discussed in this
      article. A validation of the taxonomy and conclusions drawn from this validation
      effort are described. Future research is also summarized.

PMID- 16948693
TI  - Precaution and cholera: a response to Tickner and Gouveia-Vigeant.

PMID- 16948694
TI  - Implicit attitudes toward nuclear power and mobile phone base stations: support
      for the affect heuristic.
AB  - The implicit association test (IAT) measures automatic associations. In the
      present research, the IAT was adapted to measure implicit attitudes toward
      technological hazards. In Study 1, implicit and explicit attitudes toward nuclear
      power were examined. Implicit measures (i.e., the IAT) revealed negative
      attitudes toward nuclear power that were not detected by explicit measures (i.e.,
      a questionnaire). In Study 2, implicit attitudes toward EMF (electro-magnetic
      field) hazards were examined. Results showed that cell phone base stations and
      power lines are judged to be similarly risky and, further, that base stations are
      more closely related to risk concepts than home appliances are. No differences
      between experts and lay people were observed. Results of the present studies are
      in line with the affect heuristic proposed by Slovic and colleagues. Affect seems
      to be an important factor in risk perception.

PMID- 16948695
TI  - Comparing experimental designs for benchmark dose calculations for continuous
      endpoints.
AB  - The BMD (benchmark dose) method that is used in risk assessment of chemical
      compounds was introduced by Crump (1984) and is based on dose-response modeling.
      To take uncertainty in the data and model fitting into account, the lower
      confidence bound of the BMD estimate (BMDL) is suggested to be used as a point of
      departure in health risk assessments. In this article, we study how to design
      optimum experiments for applying the BMD method for continuous data. We exemplify
      our approach by considering the class of Hill models. The main aim is to study
      whether an increased number of dose groups and at the same time a decreased
      number of animals in each dose group improves conditions for estimating the
      benchmark dose. Since Hill models are nonlinear, the optimum design depends on
      the values of the unknown parameters. That is why we consider Bayesian designs
      and assume that the parameter vector has a prior distribution. A natural design
      criterion is to minimize the expected variance of the BMD estimator. We present
      an example where we calculate the value of the design criterion for several
      designs and try to find out how the number of dose groups, the number of animals
      in the dose groups, and the choice of doses affects this value for different Hill
      curves. It follows from our calculations that to avoid the risk of unfavorable
      dose placements, it is good to use designs with more than four dose groups. We
      can also conclude that any additional information about the expected dose
      response curve, e.g., information obtained from studies made in the past, should
      be taken into account when planning a study because it can improve the design.

PMID- 16948696
TI  - Psychological determinants of reactions to food risk messages.
AB  - In recent years, European countries have witnessed a number of food crises such
      as dioxin-contaminated chicken, foot-and-mouth disease, and BSE. In such cases,
      food might be contaminated by microorganisms or chemicals that could pose a risk
      to the consumer. These cases attract media attention and might instigate the
      consumer to reduce the consumption of the allegedly contaminated products.
      Although a decline in consumption of (potentially) contaminated products has been
      observed, it is not yet clear what determines the individual's reaction to food
      risk messages. To study the psychological determinants of the reaction to food
      risk messages, a survey was conducted in the Netherlands (n= 280). Subjects had
      to imagine two situations involving chicken contamination and report how they
      would react behaviorally if this situation occurred. Risk perception, affective
      response, perceived susceptibility to foodborne disease, self-efficacy, outcome
      expectation, trust, experience with foodborne disease, and need for information
      were also assessed. It was found that 60% of the subjects would allegedly avoid
      the risks by not consuming chicken for a while and approximately 60% would seek
      additional information. Risk avoidance was significantly related to information
      seeking and the psychological determinants, especially risk perception, affective
      response, need for information, perceived susceptibility to foodborne disease,
      and trust. Seeking information was also significantly related to risk perception,
      affective response, need for information, susceptibility to foodborne disease,
      and trust, but to a lesser degree. A model describing the relationships between
      the variables was tested using AMOS. Results are presented and implications are
      discussed.

PMID- 16948697
TI  - TCDD exposure-response analysis and risk assessment.
AB  - We examined the relation between cancer mortality and time-dependent cumulative
      exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) estimated from a
      concentration- and age-dependent kinetic model of elimination, and we estimated
      incremental cancer risks at age 75. Data from the National Institute for
      Occupational Safety and Health study of 3,538 workers with occupational exposure
      to TCDD were analyzed using standardized mortality ratios and Cox regression
      procedures. Analyses adjusted for potential confounding by age, year of birth,
      and race and considered exposure lag periods of 0, 10, or 15 years. Other
      potential confounders including smoking and other occupational exposures were
      evaluated indirectly. To explore the influence of extreme values of cumulative
      TCDD ppt-years, we restricted the analysis to observations with exposure below
      the 95th percentile or used logarithmic (ln) transformed exposure values. We
      applied penalized smoothing splines to examine variation in the exposure-response
      relation across the exposure range. TCDD was not statistically significantly
      associated with cancer mortality using the full data set, regardless of the lag
      period. When we restricted the analysis to observations with exposure below the
      95th percentile, TCDD was associated positively with cancer mortality,
      particularly when a 15-year lag was applied (untransformed exposure data:
      regression coefficient , standard error (s.e.) = 1.4 x 10(-6), p < 0.05; ln
      transformed exposure data: , s.e. = 2.9 x 10(-2), p < 0.05). The estimated
      incremental lifetime risk of mortality at age 75 from all cancers was about 6 to
      more than 10 times lower than previous estimates derived from this cohort using
      exposure models that did not consider the age and concentration dependence of
      TCDD elimination.

PMID- 16948698
TI  - The role of society in engineering risk analysis: a capabilities-based approach.
AB  - This article proposes a new conceptual framework in engineering risk analysis to
      account for the net impact of hazards on individuals in a society. It analyzes
      four limitations of prevailing approaches to risk analysis and suggests a way to
      overcome them. These limitations are a result of how societal impacts are
      characteristically accounted for and valued. Prevailing approaches typically
      focus too narrowly on the consequences of natural or man-made hazards, not
      accounting for the broader societal impacts of such hazards. Such approaches lack
      a uniform and consistent metric for accounting for the impact of the
      nonquantifiable consequences (like psychological trauma or societal impacts) and
      rely upon implicit and potentially inaccurate value judgments when evaluating
      risks. To overcome these limitations, we propose an alternative, Capabilities
      Based Approach to the treatment of society in risk analysis. A similar approach
      is currently used by the United Nations to quantitatively measure the degree of
      development in countries around the world. In a Capabilities-Based Approach, the
      potential benefits and losses due to a hazard are measured and compared in a
      uniform way by using individual capabilities (functionings individuals are able,
      still able, or unable to achieve) as a metric. This Capabilities-Based Approach
      provides a foundation for identifying and quantifying the broader, complex
      societal consequences of hazards and is based on explicit, value judgments. The
      Capabilities-Based Approach can accommodate different methods or techniques for
      risk determination and for risk evaluation and can be used in assessing risk in
      diverse types of hazards (natural or man-made) and different magnitudes that
      range from minor to catastrophic. In addition, implementing a Capabilities-Based
      Approach contributes to the development of a single standard for public policy
      decision making, since a Capabilities-Based Approach is already in use in
      development economics and policy.

PMID- 16948699
TI  - An integrated model of infection risk in a health-care environment.
AB  - Certain respiratory tract infections can be transmitted by hand-to-mucous
      membrane contact, inhalation, and/or direct respiratory droplet spray. In a room
      occupied by a patient with such a transmissible infection, pathogens present on
      textile and nontextile surfaces, and pathogens present in the air, provide
      sources of exposure for an attending health-care worker (HCW); in addition, close
      contact with the patient when the latter coughs allows for droplet spray
      exposure. We present an integrated model of pertinent source-environment-receptor
      pathways, and represent physical elements in these pathways as "states" in a
      discrete-time Markov chain model. We estimate the rates of transfer at various
      steps in the pathways, and their relationship to the probability that a pathogen
      in one state has moved to another state by the end of a specified time interval.
      Given initial pathogen loads on textile and nontextile surfaces and in room air,
      we use the model to estimate the expected pathogen dose to a HCW's mucous
      membranes and respiratory tract. In turn, using a nonthreshold infectious dose
      model, we relate the expected dose to infection risk. The system is illustrated
      with a hypothetical but plausible scenario involving a viral pathogen emitted via
      coughing. We also use the model to show that a biocidal finish on textile
      surfaces has the potential to substantially reduce infection risk via the hand-to
      mucous-membrane exposure pathway.

PMID- 16948700
TI  - The evolving story of Mycobacterium tuberculosis clade members detected in fish.
AB  - Advances in molecular analyses have permitted documentation of an increasing
      spectrum of mycobacteria infecting fish. Although some of these mycobacteria are
      not closely related, several species belong to the Mycobacterium tuberculosis
      clade. One member of the clade, M. marinum, is well known as an agent of piscine
      mycobacteriosis. Three other clade species, M. shottsii, M. pseudoshottsii and M.
      'chesapeaki', have recently been identified as predominant disease agents in a
      widespread, continuing epizootic in wild striped bass of the Chesapeake Bay. A
      fifth clade member, M. ulcerans, has recently been indirectly detected in wild,
      African cichlid fish. As M. ulcerans is the third most common human mycobacterial
      infection worldwide, even such indirect evidence of M. ulcerans in fish must be
      more thoroughly investigated. Complicating the differentiation of these clade
      members is the growing recognition of intraspecies and interspecies variation in
      phenotypes, genes and virulence. Thus, researchers must be aware of the variety
      of piscine isolates within the M. tuberculosis clade. This review summarizes the
      methods of detection and differentiation for this important group of
      mycobacteria.

PMID- 16948701
TI  - Ichthyophonus-induced cardiac damage: a mechanism for reduced swimming stamina in
      salmonids.
AB  - Swimming stamina, measured as time-to-fatigue, was reduced by approximately two
      thirds in rainbow trout experimentally infected with Ichthyophonus. Intensity of
      Ichthyophonus infection was most severe in cardiac muscle but multiple organs
      were infected to a lesser extent. The mean heart weight of infected fish was 40%
      greater than that of uninfected fish, the result of parasite biomass,
      infiltration of immune cells and fibrotic (granuloma) tissue surrounding the
      parasite. Diminished swimming stamina is hypothesized to be due to cardiac
      failure resulting from the combination of parasite-damaged heart muscle and low
      myocardial oxygen supply during sustained aerobic exercise. Loss of stamina in
      Ichthyophonus-infected salmonids could explain the poor performance previously
      reported for wild Chinook and sockeye salmon stocks during their spawning
      migration.

PMID- 16948702
TI  - Experimental induction of nocardiosis in yellowtail, Seriola quinqueradiata
      Temminck and Schlegel by artificial challenge.
AB  - Challenge methods for inducing nocardiosis, caused by Nocardia seriolae in
      yellowtail, Seriola quinqueradiata, were evaluated. The first method involved
      intraperitoneal injection of 1.1 x 10(2), x 10(3) and x 10(4) cfu of N. seriolae;
      the second was by bath immersion with three different concentrations of bacterial
      suspension for 10 min; the third was by intradermal injection using a
      multipuncture device; the fourth was by oral administration using a tube; the
      fifth was based on the co-habitation of uninfected fish with others that had been
      artificially infected, i.e. intraperitoneally or by immersion for 10 min. The
      LD(50) values for the infection trials were 1.9 x 10(2) (intraperitoneal
      injection), 1.5 x 10(4) mL(-1) (immersion), 4.3 x 10(6) (intradermal injection)
      and 1.7 x 10(7) (oral administration). In the co-habitation challenge,
      mortalities were 70% and 50% in groups of non-infected fish mixed with fish
      infected by the i.p. injection and immersion methods, respectively. Fish
      challenged by intraperitoneal injection developed adhesions. Fish challenged by
      other methods did not show any gross clinical signs and moribund fish were
      similar to natural infection.

PMID- 16948703
TI  - Myocardial glycogen storage disease in farmed rainbow trout, Oncorhynchus mykiss
      (Walbaum).
AB  - This paper is the first description of a spontaneous glycogen-storage disease in
      a lower vertebrate, as previous descriptions deal with humans and other mammals,
      or fish where the condition has been experimentally induced. Affected farmed
      rainbow trout experienced increased mortality from 60 days post-startfeeding and
      displayed clinical signs of heart failure with abnormal behaviour, exophthalmia,
      distended abdomen and ventral skin petechiation. Necropsy revealed alterations in
      cardiac shape with distended atria and rounded ventricles. Microscopically, the
      compact wall of the ventricle was absent, uneven or thinner than normal. The
      cardiac myocytes contained extensive amounts of glycogen in cytoplasmic vacuoles
      as demonstrated by periodic acid-Schiff staining that was abolished by saliva
      diastase pretreatment on serial sections. Associated lesions included conspicuous
      subepicardial and myocardial vascularization, epicardial thickening and necrosis
      of the ventricular compactum/spongiosum interphase. The lesions in cardiac
      myocytes had a striking resemblance to glycogenosis type II (Pompe disease), a
      rare autosomal recessive lysosomal storage disease in humans. This condition was
      more severe and mortality was higher in a replicate/parallel fish group treated
      perorally with 17alpha-methyltestosterone to produce all-female progeny,
      indicating that the hormone treatment aggravated the condition resulting in
      earlier and more severe manifestation of the disease in this group.

PMID- 16948704
TI  - Characterization of Edwardsiella tarda strains isolated from turbot, Psetta
      maxima (L.).
AB  - The biochemical, serological and molecular characteristics of a group of 21
      Edwardsiella tarda strains isolated from turbot, Psetta maxima, in two different
      areas of Europe were analysed and compared with a total of 13 strains of this
      bacterial species with different geographical and host origins. All the turbot
      isolates were biochemically identical to the E. tarda strains included as
      reference. The use of different techniques including microagglutination, dot blot
      and Western blot of lipopolysaccharides allowed us to determine that all the
      turbot isolates constitute an homogeneous and distinctive serological group.
      Genetic analysis by randomly amplified polymorphic DNA (RAPD) analysis
      demonstrated that although the E. tarda strains from turbot were compiled in a
      unique group using the primers P3 and P6, two clonal lineages could be detected
      when oligonucleotides P4 and P5 were employed.

PMID- 16948705
TI  - Amoebic gill disease (AGD)-affected Atlantic salmon, Salmo salar L., are
      resistant to subsequent AGD challenge.
AB  - There is inconsistent evidence of resistance of Atlantic salmon, Salmo salar L.,
      to amoebic gill disease (AGD). Here, evidence is presented that demonstrates that
      Atlantic salmon exposed and subsequently challenged with AGD are more resistant
      than naive control fish. Seventy-three per cent of Atlantic salmon previously
      exposed to AGD survived to day 35 post-challenge compared with 26% exposed to
      Neoparamoeba sp. for the first time, yet the gill pathology of surviving naive
      control or previously exposed fish was not significantly different. Development
      of resistance to AGD is associated with anti-Neoparamoeba sp. antibodies that
      were detectable in serum of 50% of surviving Atlantic salmon previously exposed
      to AGD. However, anti-Neoparamoeba sp. antibodies were not detectable in
      cutaneous mucus of resistant fish. Increased resistance of Atlantic salmon after
      secondary Neoparamoeba sp. infection and detection of specific serum antibodies
      provides support for the development of a vaccine for AGD.

PMID- 16948706
TI  - Temperature effects on the development of Enteromyxum spp. (Myxozoa) in
      experimentally infected tiger puffer, Takifugu rubripes (Temminck & Schlegel).
AB  - The effects of water temperature on the development of the enteric myxosporeans,
      Enteromyxum fugu and Enteromyxum leei, were investigated in experimentally
      infected tiger puffer, Takifugu rubripes. After naive tiger puffer were fed gut
      tissue infected with both E. fugu and E. leei, they were divided into separate
      tanks and kept at different constant temperature regimes between 10 and 25
      degrees C. Regardless of the water temperature tested, E. fugu was consistently
      detected with a high prevalence of infection (60-100%), although no sporulation
      occurred at 10 and 15 degrees C. Development of E. leei and the onset of disease
      were suppressed by low water temperatures (<15 degrees C). However, a temperature
      increase to 20 degrees C promoted the development of E. leei, followed by an
      increase of disease rate in the fish. The present study demonstrates that water
      temperatures below 15 degrees C have an inhibitory effect on the development of
      E. fugu and E. leei, resulting in suppression of enteromyxosis at low
      temperatures.

PMID- 16948707
TI  - Studies on the inactivation of white spot syndrome virus of shrimp by physical
      and chemical treatments, and seaweed extracts tested in marine and freshwater
      animal models.

PMID- 16948709
TI  - What is IAQ?
AB  - In spaces for human occupancy indoor air quality (IAQ) is often defined as the
      extent to which human requirements are met. But what requirements do people have
      in relation to indoor air? The desire is that the air be perceived as fresh and
      pleasant, that it has no negative impact on their health, and that the air is
      stimulating and promotes their work, i.e. it increases their productivity and the
      learning of their children in the classroom at school. Present ventilation
      standards and guidelines do not care about productivity and learning and have the
      very modest requirement that the indoor air shall be 'acceptable,' meaning that
      the most sensitive group of persons (usually 20%) perceive the air as
      unacceptable while the remaining less sensitive persons may find the air barely
      acceptable. With such a modest aim it is not surprising that comprehensive field
      studies in many countries in buildings in which ventilation standards are met
      show high percentages of dissatisfied persons and of those suffering from sick
      building syndrome symptoms. Recent studies show that improvement of IAQ by a
      factor of 2-7 compared with existing standards increases office productivity and
      school learning significantly, while decreasing the risk of allergic symptoms and
      asthma in homes. To make indoor air acceptable, even for the most sensitive
      persons, an improvement of 1-2 orders of magnitude may be required. The paper
      will discuss the development of new methods that can provide such substantial
      improvements of IAQ while maintaining or even decreasing ventilation and energy
      usage. A paradigm shift is required and further future shifts are foreseen where
      we learn how to make indoor air equally fresh and pleasant as outdoors when it is
      best. Or even better, i.e. 'out of this world.' PRACTICAL IMPLICATIONS: The paper
      estimates an enormous potential for improving IAQ in practice utilizing new
      emerging technologies. This will enable us to provide IAQ which is acceptable
      even for the most sensitive persons. Already modest improvements compared to
      present minimum standards and typical conditions in practice can significantly
      decrease the risk of asthma/allergy in homes, improve learning in schools and
      increase productivity.

PMID- 16948710
TI  - Droplet fate in indoor environments, or can we prevent the spread of infection?
AB  - When considering how people are infected and what can be done to prevent the
      infections, answers from many disciplines are sought: microbiology, epidemiology,
      medicine, engineering, and physics. There are many pathways to infection spread,
      and among the most significant from the epidemiological point of view is airborne
      transport. Microorganisms can become airborne when droplets are generated during
      speech, coughing, sneezing, vomiting, or atomization of feces during sewage
      removal. The fate of the droplets is governed by the physical principles of
      transport, with droplet size being the most important factor affecting their
      dispersion, deposition on surfaces and determining the survival of microorganisms
      within the droplets. In addition, physical characteristics of the indoor
      environment as well as the design and operation of building ventilation systems
      are of critical importance. Do we understand the mechanisms of infection spread
      and can we quantify the droplet dynamics under various indoor conditions?
      Unfortunately no, as this aspect of infection spread has attracted surprisingly
      little scientific interest. However, investigations of numerous cases in which a
      large number of people were infected show how critical the physics of
      microorganism spread can be. This paper reviews the state of knowledge regarding
      mechanisms of droplet spread and solutions available to minimize the spread and
      prevent infections. PRACTICAL IMPLICATIONS: Every day tens of millions of people
      worldwide suffer from viral infections of different severity at immense economic
      cost. There is, however, only minimal understanding of the dynamics of virus
      laden aerosols, and so the ability to control and prevent virus spread is
      severely reduced, as was clearly demonstrated during the recent severe acute
      respiratory syndrome epidemic. This paper proposes the direction to significantly
      advance fundamental and applied knowledge of the pathways of viral infection
      spread in indoor atmospheric systems, through a comprehensive multidisciplinary
      approach and application of state-of-the-art scientific methods. Knowledge gained
      will have the potential to bring unprecedented economical gains worldwide by
      minimizing/reducing the spread of disease.

PMID- 16948711
TI  - Impact of dynamic airflow on human thermal response.
AB  - Airflow fluctuation is an important factor affecting indoor thermal environments
      and human thermal response. In this study, dynamic airflows with different
      fluctuation characteristics were generated by a dynamic air supply terminal. The
      influence of three different kinds of airflows, constant airflow, simulated
      natural airflow and sinusoidal airflow, on thermal comfort was studied.
      Subjective experiments indicated that a dynamic airflow can cause a stronger cold
      sensation, and that air movement with 1/f fluctuations similar to natural wind is
      more acceptable than other dynamic airflows in warm environments. Moreover, the
      impact of draughts in dynamic airflows on human thermal response is different in
      neutral-warm (30 degrees C) and cool-neutral (26 degrees C) thermal environments.
      PRACTICAL IMPLICATIONS: By means of a dynamic air supply terminal it is possible
      to generate artificial airflows that simulate natural wind indoors. This kind of
      airflow with higher velocity is more comfortable and causes less draught
      sensation than the constant airflows supplied by conventional fans. While the
      cooling effect of this airflow is utilized in the built environment, the design
      temperature of air-conditioning system can be increased and the amount of energy
      consumption can be reduced dramatically.

PMID- 16948712
TI  - Influence of movements on contaminant transport in an operating room.
AB  - The influence of persons' movements on contaminant transport during an orthopedic
      surgical operation is examined. Orthopedic surgical operations require an ultra
      clean environment usually provided by a LAF device (laminar airflow). During hip
      replacements bone cement is sometimes applied. Due to practical reasons cement
      mixing is performed outside the LAF area. During the cement transport from the
      mixing location to the surgeon there is a potential risk of bacterial transport
      to the clean zone. This phenomenon is examined by smoke visualization and
      computational fluid dynamics (CFD). The movements are modeled by CFD using
      distributed momentum sources as well as a turbulent kinetic energy source. A
      significant risk of contaminant transport from the less clean zone to the ultra
      clean zone is found. The results indicate that it is possible to simulate the
      influence of movements using a relatively simple CFD model that considers the
      significant influence of a transient phenomenon in an approximate way. PRACTICAL
      IMPLICATIONS: In real-life ventilated enclosures like operating rooms movements
      take place. Persons' movements may influence the local flow field as well as the
      contaminant field substantially. Most often movements are ignored in simulations
      due to the complexity of the phenomenon. This paper presents an indirect and
      simple method to consider the influence of movements that may enable modelers to
      include this important phenomenon in the engineering application of CFD. This may
      improve practical risk assessment--for instance risk assessment of unintended
      transport of bacteria during orthopedic surgical operations that may jeopardize
      the hygiene.

PMID- 16948713
TI  - Material odor-odoractive compounds identified in different materials--the
      surprising similarities with certain foods, possible sources and hypotheses on
      their formation.
AB  - Increased efforts have been undertaken by manufacturers to reveal the secrets of
      material odors, the structure of the odorants responsible, with regard to finding
      out the source(s) of odor and possible starting points for odor reduction, and
      therewith product improvement, increased consumer satisfaction and improved
      indoor air quality. The identification of odor-active compounds in materials by
      means of gas chromatography-olfactometry (GC-O, also called GC-sniffing),
      performed at the Fraunhofer Institute for Building Physics (IBP) during the
      previous years, showed surprising similarities between certain odorants found in
      materials and those previously identified in certain kinds of food. Examples of
      important odorants found in different material samples and similarities with food
      odorants were analyzed. Odorant sources are indicated as regards materials, and
      possible conditions and mechanisms of formation suggested to show starting points
      for odor reduction and odor improvement in material development. PRACTICAL
      IMPLICATIONS: If technical materials are planned to be used indoors and if they
      spread a distinct odor, the analysis of the compounds contained and emitted by
      this material using gas chromatography-olfactometry is a means to help reveal the
      compounds being responsible for that odor. The exact knowledge of the structure
      of the odorants is the prerequisite for drawing conclusions on possible sources
      and formation mechanisms and to reveal starting points for odor reduction and
      product improvement, e.g. by changing ingredients or production conditions. This
      contributes to an improvement of indoor air quality. Furthermore, quite often the
      concentrations of certain single odorants found in materials can be very low and
      the same odorants can be part of other well-known food flavors. This information
      might be useful to reduce consumers' fears of a possible impairment of their
      health in the future.

PMID- 16948714
TI  - Multivariate evaluation of VOCs in buildings where people with non-specific
      building-related symptoms perceive health problems and in buildings where they do
      not.
AB  - Volatile organic compounds (VOCs) were sampled in buildings where people with non
      specific building-related symptoms perceive health problems and in buildings
      where they do not. In total, nine persons and 34 buildings were included in the
      study. The obtained VOC data was evaluated using multivariate methods, to
      investigate possible systematic differences in air quality of 'problem' and 'non
      problem' buildings. All individual compounds were included as variables in a
      multivariate partial least squares (PLS) data analysis. 'Problem' and 'non
      problem' buildings separated into two distinct groups, showing that air samples
      of the two groups of building were chemically different. PRACTICAL IMPLICATIONS:
      The study showed that there was an identifiable systematic difference in the
      collected VOC data between buildings causing and not causing problems for people
      with non-specific building-related symptoms (also called sick building syndrome,
      SBS). This is an important indication that even such volatile organic compounds
      that can be sampled by commonly used adsorbents are of importance for the
      presence of such symptoms. By coordination of procedures for sampling and
      analysis of VOCs in buildings between laboratories, to get large datasets and
      more general models, the method can become a useful diagnostic measure in
      evaluating indoor air and to identify chemical compounds and sources that
      contribute to SBS problems.

PMID- 16948715
TI  - Indoor climate, psychosocial work environment and symptoms in open-plan offices.
AB  - To study the indoor climate, the psychosocial work environment and occupants'
      symptoms in offices a cross-sectional questionnaire survey was made in 11
      naturally and 11 mechanically ventilated office buildings. Nine of the buildings
      had mainly cellular offices; five of the buildings had mainly open-plan offices,
      whereas eight buildings had a mixture of cellular, multi-person and open-plan
      offices. A total of 2301 occupants, corresponding to a response rate of 72%,
      completed a retrospective questionnaire. The questionnaire comprised questions
      concerning environmental perceptions, mucous membrane irritation, skin
      irritation, central nervous system (CNS) symptoms and psychosocial factors.
      Occupants in open-plan offices are more likely to perceive thermal discomfort,
      poor air quality and noise and they more frequently complain about CNS and mucous
      membrane symptoms than occupants in multi-person and cellular offices. The
      association between psychosocial factors and office size was weak. Open-plan
      offices may not be suited for all job types. PRACTICAL IMPLICATION: Open-plan
      offices may be a risk factor for adverse environmental perceptions and symptoms.

PMID- 16948716
TI  - "Cesarean Delivery on Maternal Request": was the NIH conference based on a faulty
      premise?

PMID- 16948717
TI  - Infant and neonatal mortality for primary cesarean and vaginal births to women
      with "no indicated risk," United States, 1998-2001 birth cohorts.
AB  - BACKGROUND: The percentage of United States' births delivered by cesarean section
      has increased rapidly in recent years, even for women considered to be at low
      risk for a cesarean section. The purpose of this paper is to examine infant and
      neonatal mortality risks associated with primary cesarean section compared with
      vaginal delivery for singleton full-term (37-41 weeks' gestation) women with no
      indicated medical risks or complications. METHODS: National linked birth and
      infant death data for the 1998-2001 birth cohorts (5,762,037 live births and
      11,897 infant deaths) were analyzed to assess the risk of infant and neonatal
      mortality for women with no indicated risk by method of delivery and cause of
      death. Multivariable logistic regression was used to model neonatal survival
      probabilities as a function of delivery method, and sociodemographic and medical
      risk factors. RESULTS: Neonatal mortality rates were higher among infants
      delivered by cesarean section (1.77 per 1,000 live births) than for those
      delivered vaginally (0.62). The magnitude of this difference was reduced only
      moderately on statistical adjustment for demographic and medical factors, and
      when deaths due to congenital malformations and events with Apgar scores less
      than 4 were excluded. The cesarean/vaginal mortality differential was widespread,
      and not confined to a few causes of death. CONCLUSIONS: Understanding the causes
      of these differentials is important, given the rapid growth in the number of
      primary cesareans without a reported medical indication.

PMID- 16948718
TI  - Does supplementary prenatal nursing and home visitation support improve resource
      use in a universal health care system? A randomized controlled trial in Canada.
AB  - BACKGROUND: The addition of supplementary prenatal support may improve the health
      and well-being of high-risk women and families. The objective of this randomized
      controlled trial was to examine the impact of supplementary prenatal care on
      resource use among a community-based population of pregnant women. METHODS:
      Pregnant women from three urban maternity clinics were randomized (a) to current
      standard of physician care, (b) to current standard of care plus consultation
      with a nurse, or (c) to (b) plus consultation with a home visitor. Participants
      were 1,352 women who received 3 telephone interviews. The primary outcome was
      resource use (e.g., attended prenatal classes, used nutritional counseling).
      RESULTS: Overall, those in the nurse intervention group were more likely to
      attend an "Early Bird" prenatal class and parenting classes, and to use nutrition
      counseling and agencies that assist with child care. Women provided with extra
      nursing and home visitation supports were more likely to use a written resource
      guide, nutrition counseling, and agencies that assist with child care. Among
      women at higher risk (e.g., language barriers, young maternal age, low income),
      the nurse intervention significantly increased use of early prenatal classes,
      whereas the nurse and home visitor intervention significantly increased use of
      the written resource guide and nutrition counseling. The intervention
      substantially increased the amount of information received on numerous pregnancy
      related topics but had little impact on resource use for mental health and
      poverty-related needs. Among those with added support, resource use among low
      risk women was generally greater than among high-risk women. CONCLUSIONS:
      Additional support provided by nurses, or nurses and home visitors, can
      successfully address informational needs and increase the likelihood that women
      will use existing community-based resources. This finding was true even for high
      risk women, although this intervention did not reduce the difference in resource
      use between high- and low-risk women.

PMID- 16948719
TI  - Do physicians and their relatives have a decreased rate of cesarean section? A 4
      year population-based study in Taiwan.
AB  - BACKGROUND: The increased rate of cesarean deliveries may be partly due to a lack
      of consumer knowledge. Assuming that physicians and their relatives are well
      informed of the risks and benefits associated with the different methods of
      delivery, our goal was to compare cesarean rates between female physicians,
      female relatives of physicians, and women with high socioeconomic status in
      Taiwan. METHODS: Two subgroups of 588 female physicians and 5,021 relatives of
      physicians aged 20 to 50 years were compared with 93,737 pregnant women with a
      monthly wage 40,000 dollars New Taiwan (NT) dollars or more as identified in
      nationwide National Health Insurance databases of Taiwan from 2000 to 2003.
      RESULTS: Female physicians (adjusted odds ratio 0.66; 95% CI 0.47, 0.93) and
      female relatives of physicians (adjusted odds ratio 0.84; 95% CI 0.74, 0.95) were
      significantly less likely to undergo a cesarean section than other high
      socioeconomic status women, adjusted for clinical and nonclinical factors.
      CONCLUSIONS: In this study, the cesarean delivery rate was lower among women who
      may have greater access to medical knowledge. However, the lower rates observed
      among female physicians and physician relatives in Taiwan are still considerably
      higher than the national averages of many countries. This finding suggests that
      other than information, practice patterns, and social and cultural milieu may
      play a role.

PMID- 16948720
TI  - Surveillance of cesarean section deliveries, New Jersey, 1999-2004.
AB  - BACKGROUND: Nationally and in New Jersey, the cesarean delivery rate has been
      increasing steadily for nearly a decade, and especially since 1999. The purpose
      of this study was to describe recent trends in cesarean section delivery in New
      Jersey. METHODS: Data on delivery method, medical indications and patient
      characteristics were extracted from electronic birth certificate files. RESULTS:
      Cesarean section deliveries increased as a proportion of live births by 6 percent
      annually. Growth was roughly uniform across Robson's clinical classification.
      Repeat cesareans contributed only proportionately to the overall trend. The
      greatest acceleration was observed for procedures without trial of labor, and in
      medical situations where cesarean delivery had been relatively rare. CONCLUSIONS:
      Medical indications recorded on the birth certificate explained little of the
      rapid growth in utilization of cesarean delivery, since trends were comparable in
      most categories we examined. A sustained autonomous shift in practice patterns,
      patient preferences, or both seems the most likely driver of the overall trend.

PMID- 16948721
TI  - Systematic review of the literature on postpartum care: effectiveness of
      postpartum support to improve maternal parenting, mental health, quality of life,
      and physical health.
AB  - BACKGROUND: Postpartum support is recommended to prevent infant and maternal
      morbidity. This review examined the published evidence of the effectiveness of
      postpartum support programs to improve maternal knowledge, attitudes, and skills
      related to parenting, maternal mental health, maternal quality of life, and
      maternal physical health. METHODS: MEDLINE, Cinahl, PsycINFO, and the Cochrane
      Library were searched for randomized controlled trials of interventions initiated
      from immediately after birth to 1 year in postnatal women. The initial literature
      search was done in 1999 and was enhanced in 2003 and 2005. Studies were
      categorized based on the the above outcomes. Data were extracted in a systematic
      manner, and the quality of each study was reviewed. RESULTS: In the 1999 search,
      9 studies met the inclusion criteria. The 2003 and 2005 searches identified 13
      additional trials for a total of 22 trials. Universal postpartum support to
      unselected women at low risk did not result in statistically significant
      improvements for any outcomes examined. Educational visits to a pediatrician
      showed statistically significant improvements in maternal-infant parenting skills
      in low-income primiparous women. In women at high risk for family dysfunction and
      child abuse, nurse home visits combined with case conferencing produced a
      statistically significant improvement in home environment quality using the HOME
      (Home Observation for Measurement of the Environment) program. Similarly, in
      women at high risk for either family dysfunction or postpartum depression, home
      visitation or peer support, respectively, produced a statistically significant
      reduction in Edinburgh Postnatal Depression Scale scores (difference - 2.23, 95%
      CI -3.72 to -0.74, p= 0.004; and 15.0% vs 52.4%, OR 6.23, 95% CI 1.40 to 27.84,
      p= 0.01, respectively). Educational programs reduced repeat unplanned pregnancies
      (12.0% vs 28.3%, p= 0.003) and increased effective contraceptive use (RR 1.35,
      95% CI 1.09 to 1.68, p= 0.007). Maternal satisfaction was higher with home
      visitation programs. CONCLUSIONS: No randomized controlled trial evidence was
      found to endorse universal provision of postpartum support to improve parenting,
      maternal mental health, maternal quality of life, or maternal physical health.
      There is some evidence that high-risk populations may benefit from postpartum
      support.

PMID- 16948722
TI  - Maternal request for cesarean section due to fear of birth: can it be changed
      through crisis-oriented counseling?
AB  - BACKGROUND: A psychosocial team was established to meet the needs of an
      increasing number of pregnant women referred for fear of birth who wished a
      planned cesarean. This study describes the intervention, the women's psychosocial
      problems in relation to degree of fear of birth, changes in their wishes for mode
      of birth and birth outcome, women's satisfaction with the intervention, and their
      wishes for future births. METHODS: The study sample comprised 86 pregnant women
      with fear of birth and a request for planned cesarean, who were referred for
      counseling by a psychosocial team at the University Hospital of North Norway in
      the period 2000-2002. Data were gathered from referral letters, from antenatal
      and intrapartum care records, and from a follow-up survey conducted 2 to 4 years
      after the birth in question. RESULTS: Fear of birth was accompanied by extensive
      psychosocial problems in most women. Ninety percent had experienced anxiety or
      depression, 43 percent had eating disturbances, and 63 percent had been subjected
      to abuse. Twenty-four percent of those with psychiatric conditions had previously
      been in treatment. After the intervention, 86 percent changed their original
      request for cesarean section and were prepared to give birth vaginally. The
      follow-up survey confirmed long-term satisfaction with having changed their
      request for a cesarean delivery. Of these, 69 percent gave birth vaginally and 31
      percent were delivered by cesarean for obstetrical indications. CONCLUSIONS:
      Impending birth activates previous traumatic experiences, abuse, and psychiatric
      disorders that may give rise to fear of vaginal birth. When women were referred
      to a specialist service for fear of birth and request for cesarean, they became
      conscious of, and to some degree worked through, the causes of their fear, and
      most preferred vaginal birth. They remained pleased with their choice later.

PMID- 16948723
TI  - Systematic review of nulliparous women's views of planned cesarean birth: the
      missing component in the debate about a term cephalic trial.
AB  - BACKGROUND: The suggestion that planned cesarean birth is gaining acceptance
      among women has led some physicians to advocate the need for a trial of primary
      planned cesarean section versus planned vaginal birth in healthy women with
      singleton cephalic pregnancies at term. This paper reviews published studies of
      nulliparous women's views of mode of birth collected in the antenatal period,
      examining why women may express a preference for cesarean birth and exploring
      implications for the debate about the need for a trial. METHODS: A systematic
      literature review was undertaken of Cochrane, CINAHL, EMBASE, MEDLINE, and
      PsycINFO using the MeSH heading "cesarean section" and four free text spellings
      of "cesarean," or "birth" or "delivery," near truncated synonyms of 17 words
      meaning expressed preference. Studies of nulliparous women with a medical
      indication for cesarean birth, studies where a woman's preference for mode of
      birth was reported in the postpartum period, surveys of midwives or
      obstetricians, and opinion and non-English language papers were all excluded.
      RESULTS: Nine papers were included in the review, which reported rates of women
      expressing a preference for cesarean birth that ranged from 0 to 100 percent at
      recruitment. However, the papers raised specific methodological, conceptual, and
      cultural issues that may have influenced women's preferences for mode of birth in
      the populations studied. These issues included the timing and frequency of data
      collection, complexity of factors determining individual women's decision making,
      and influence of societal norms. CONCLUSIONS: Little evidence is available that
      an increasing cultural acceptance of cesarean delivery will bring about support
      for a trial among pregnant nulliparous women. Further qualitative research
      investigating the influence of both obstetric and psychosocial factors on women's
      views of vaginal and cesarean birth is required.

PMID- 16948724
TI  - Back to the future? A critical commentary on the 2003 U.S. National standard
      certificate of live birth.
AB  - Vital statistics documents for the United States have been revised approximately
      decennially throughout the past century. In this commentary we review the
      contents of the 2003 revision of the national standard certificate of live birth,
      focusing on changes from the certificates in use nationally since 1989, and
      identifying strengths and weaknesses of key data elements. Additional federal
      state partnership funding is imperative to support the transition to the new
      standard certificates, and to ensure a focus on data quality at the state and
      national levels.

PMID- 16948726
TI  - In the literature: pushing in the wrong direction.

PMID- 16948725
TI  - Why do women go along with this stuff?
AB  - PREFACE: Normal childbirth has become jeopardized by inexorably rising
      interventions around the world. In many countries and settings, cesarean surgery,
      labor induction, and epidural analgesia continue to increase beyond all
      precedent, and without convincing evidence that these actions result in improved
      outcomes (1,2). Use of electronic fetal monitoring is endemic, despite evidence
      of its ineffectiveness and consequences for most parturients (1,3); ultrasound
      examinations are too often done unnecessarily, redundantly, or for frivolous
      rather than indicated reasons (4); episiotomies are still routine in many
      settings despite clear evidence that this surgery results in more harm than good
      (5); and medical procedures, unphysiological positions, pubic shaving and enemas,
      intravenous lines, enforced fasting, drugs, and early mother-infant separation
      are used unnecessarily (1). Clinicians write and talk about the ideal of evidence
      based obstetrics, but do not practice it consistently, if at all. Why do women go
      along with this stuff? In this Roundtable Discussion, Part 2, we asked some
      maternity care professionals and advocates to discuss this question.

PMID- 16948727
TI  - Sheila Kitzinger's letter from Europe: what makes a good mother? Is that the only
      question?

PMID- 16948731
TI  - A placebo-controlled, crossover comparison of oral triazolam prior to sham
      patient-activated shock delivery during sinus rhythm in a group of patients with
      recurrent atrial fibrillation.

PMID- 16948733
TI  - An excellent review about inherited conduction system abnormalities.

PMID- 16948735
TI  - Does it all go up in smoke? Cigarette smoking and tachyarrhythmias.

PMID- 16948737
TI  - Is electrode catheter ablation-induced phrenic nerve injury really a benign
      condition?

PMID- 16948736
TI  - Mortality following defibrillator implantation in patients with renal
      insufficiency.
AB  - INTRODUCTION: Patients with renal insufficiency have an increased risk of
      atherosclerotic coronary artery disease, cardiovascular events, and sudden
      cardiac death. Due to under-representation of patients with renal disease in
      large clinical trials, outcomes of implantable cardioverter defibrillator (ICD)
      implantation in this group remain unclear. METHODS AND RESULTS: Inpatient and
      ambulatory records were reviewed for 741 consecutive patients undergoing 947
      defibrillator implants or replacements at Department of Defense Medical
      Facilities. Demographics, medical history, and mortality were reviewed. The mean
      age of the cohort was 64 +/- 14 years and 599 (80.8%) were male. There were 173
      patients (23.3%) with chronic renal insufficiency, 22 (3.0%) undergoing
      hemodialysis, and 546 (73.7%) without reported renal disease. The mean number of
      annual hospital admissions for heart failure among patients with and without
      renal failure was 3.8 +/- 4.0 versus 1.2 +/- 1.9 (P < 0.0001), respectively. The
      1-year survival for those without renal insufficiency was 96.6%, compared to
      87.8% for those with chronic renal insufficiency, and 88.7% for those undergoing
      hemodialysis. Multivariate analysis demonstrated a significant association
      between mortality among ICD patients and renal insufficiency, independent of
      coexisting congestive heart failure, ischemic cardiomyopathy, and diabetes
      mellitus (P < 0.0001). CONCLUSIONS: Among ICD recipients, those with renal
      insufficiency have a significantly higher mortality rate than those without renal
      insufficiency. Among a cohort of patients with ICDs, those with known renal
      insufficiency have higher rates of health care resource utilization and more
      heart failure admissions. Development of a national registry for ICDs should
      include data with regard to renal function.

PMID- 16948738
TI  - Morphologic characteristics of the left atrial appendage, roof, and septum:
      implications for the ablation of atrial fibrillation.
AB  - INTRODUCTION: The left atrium (LA) ablation in different regions, including LA
      appendage (LAA), LA roof, and LA septum, has recently been proposed to improve
      the success rate of treating patients with atrial fibrillation (AF). The purpose
      of this study was to investigate the anatomy of LAA, LA roof, and LA septum,
      using computed tomography (CT). METHODS AND RESULTS: Multidetector CT scan was
      used to depict the LA in 47 patients with drug-refractory paroxysmal AF (39
      males, age = 50 +/- 12 years) and 49 control subjects (34 males, age = 54 +/- 11
      years). The area of LAA orifice, neck, and the length of roof line were greater
      in AF group than in control subjects. Three types of LAA locations and two types
      of LAA ridges were observed. Higher incidence of inferior LAA was noted in AF
      patients. The different morphologies of LA roof were described. Roof pouches were
      revealed in 15% of AF and 14% of controls. Moreover, we found septal ridge in 32%
      of AF and 23% of controls. CONCLUSIONS: Considerable variations of LAA and LA
      roof morphologies were demonstrated. Peculiar structures, including roof pouches
      and septal ridges, were delineated by CT imaging. These findings were important
      for determining the strategy of AF ablation and avoiding the procedure-related
      complications.

PMID- 16948739
TI  - External and endoluminal analysis of left atrial anatomy and the pulmonary veins
      in three-dimensional reconstructions of magnetic resonance angiography: the full
      insight from inside.
AB  - INTRODUCTION: The detailed knowledge of the individual pulmonary vein (PV)
      anatomy may help to prevent serious complications during PV isolation (PVI). The
      purpose of this study was to determine the geometry of the PV ostia and their
      spatial relation to adjacent structures in external (ex 3D) and endoluminal (en
      3D) three-dimensional reconstructions of magnetic resonance angiographies (MRAs).
      METHODS AND RESULTS: Ex 3D and en 3D of the left atrium (LA) and the PVs of 28
      patients were calculated. Diameters and the shape of PV ostia were assessed. In
      addition, the distances between ipsilateral PV ostia, the LA isthmus line, the
      roof line and the distance between the left PV and the LA appendage (LAA) were
      measured. Both ex 3D and en 3D are useful tools to determine the dimensions and
      the geometry of PVs. En 3D facilitates the identification of common PV ostia
      (15/28 patients). In en 3D, ipsilateral PV ostia are separated by a narrow
      myocardial ridge of less than 4 mm in 19/38 PVs (mean 4.3 +/- 1 mm; 4.6 +/- 2 mm
      with ex 3D). LAA and the LPV ostia are separated by a ridge of less than 4 mm in
      12/28 PVs measured with en 3D (4.8 +/- 2 mm; 6.4 +/- 2 mm with ex 3D).
      CONCLUSIONS: Both ex 3D and en 3D reconstructions of MRA precisely visualize the
      complex LA anatomy. Exact determination of PV ostial geometry is facilitated with
      en 3D and provides important anatomical information for the PVI strategy.
      According to our data, individual encircling of every PV is strongly discouraged.

PMID- 16948740
TI  - Frequency mapping of the pulmonary veins in paroxysmal versus permanent atrial
      fibrillation.
AB  - INTRODUCTION: The pulmonary veins (PVs) are a dominant source of triggers
      initiating atrial fibrillation (AF). While recent evidence implicates these
      structures in the maintenance of paroxysmal AF, their role in permanent AF is not
      known. The current study aims to compare the contribution of PV activity to the
      maintenance of paroxysmal and permanent AF. METHODS AND RESULTS: Thirty-four
      patients with paroxysmal AF (n = 20) or permanent AF (n = 14) undergoing ablation
      were studied. Prior to ablation, 32 seconds of electrograms were acquired from
      each PV and the coronary sinus (CS). The frequency of activity of each PV and CS
      was defined as the highest amplitude frequency on spectral analysis. The effects
      of ablation on the AF cycle length (AFCL) and frequency and on AF termination
      were determined. Significant differences were observed between paroxysmal and
      permanent AF. Paroxysmal AF demonstrates higher frequency PV activity (11.0 +/-
      3.1 vs 8.8 +/- 3.0 Hz; P = 0.0003) but lower CS frequency (5.8 +/- 1.2 vs 6.9 +/-
      1.4 Hz; P = 0.01) and longer AFCL (182 +/- 17 vs 158 +/- 21 msec; P = 0.002),
      resulting in greater PV to atrial frequency gradient (7.2 +/- 2.2 vs 4.2 +/- 2.9
      Hz; P = 0.006). PV isolation in paroxysmal AF resulted in a greater decrease in
      atrial frequency (1.0 +/- 0.7 vs -0.05 +/- 0.4 Hz; P < 0.0001), greater
      prolongation of the AFCL (49 +/- 35 vs 5 +/- 6 msec; P < 0.0001), and more
      frequent AF termination (11/20 vs 0/14; P = 0.0007) compared to permanent AF.
      CONCLUSION: Paroxysmal AF is associated with higher frequency PV activity and
      lesser CS frequency compared to permanent AF. Isolation of the PVs had a greater
      impact on the fibrillatory process in paroxysmal AF compared to permanent AF,
      suggesting that while the PVs have a role in maintaining paroxysmal AF, these
      structures independently contribute less to the maintenance of permanent AF.

PMID- 16948741
TI  - When is ablation of AV nodal reentrant tachycardia high risk?

PMID- 16948742
TI  - The normal effects of epinephrine and isoproterenol on heart rate and QT
      interval: role in unmasking the long QT syndrome.

PMID- 16948743
TI  - Management of far-field R wave sensing for the avoidance of inappropriate mode
      switch in dual chamber pacemakers: results of the FFS-test study.
AB  - BACKGROUND AND OBJECTIVE: Far-field R wave sensing (FFS) in the atrial channel of
      dual chamber pacemakers is a relevant source for inappropriate mode switch from
      the DDD mode to the DDI or VDI mode. Inappropriate loss of atrioventricular
      synchrony due to false positive mode switch is hemodynamically disadvantageous,
      may induce atrial tachyarrhythmias, can lead to pacemaker syndrome, and impairs
      the reliability of pacemaker Holter data. The aim of the study was to determine
      whether individual adjustment of the postventricular atrial blanking period
      (PVAB) based on an additional test is effective in avoiding inappropriate mode
      switch due to FFS when compared with standard programming of the PVAB. METHODS: A
      total of 207 patients were supplied with a St. Jude Medical Identity DR or
      Identity ADx DR dual chamber pacemaker for sinus nodal disease (n = 84),
      atrioventricular block (n = 79), binodal disease (n = 35), or other indications
      (n = 9). At hospital discharge, they were randomized to an individually optimized
      PVAB (n = 100) or to a control group with the PVAB left at the nominal of 100
      msec (n = 107). Primary endpoint was the occurrence of inappropriate mode switch
      due to FFS within 3 months after pacemaker implantation assessed by stored
      electrograms of the pacemaker. RESULTS: At the 3-month follow-up, 28/107 (26%)
      patients with the standard programming of the PVAB showed at least one episode of
      inappropriate mode switch due to FFS versus 10/100 (10%) patients with optimized
      PVAB (P < 0.01). The optimized PVAB was shorter than the nominal PVAB in about
      one-third of patients and longer in about two-third of patients. Different atrial
      lead localizations were not associated with the occurrence of inappropriate mode
      switch. CONCLUSIONS: Individual adjustment of the PVAB significantly reduces the
      incidence of inappropriate mode switch due to FFS.

PMID- 16948744
TI  - A simple faint?

PMID- 16948745
TI  - Tissue Doppler imaging analysis at pre-cardioversion time predicts recurrent
      atrial fibrillation: a 12-month follow-up study.
AB  - INTRODUCTION: Tissue Doppler imaging (TDI) has been extensively used in several
      clinical settings. We aimed to investigate whether TDI can predict recurrent
      atrial fibrillation (AF). METHODS AND RESULTS: Seventy-four consecutive patients
      (aged 62.6 +/- 11.7 years) with AF (>48 hours and <6 months of duration) who
      underwent successful external electrical direct current cardioversion and 20
      healthy individuals were enrolled. Conventional echocardiography and TDI were
      prospectively performed before cardioversion. Based on a cutoff point of 5.43
      cm/sec for the negative systolic wave velocity (NSWV), derived by the normal
      controls (mean + 2 SD), patients were divided into Group I (36 patients) with a
      NSWV >5.43 cm/sec and Group II (38 patients) with NSWV <or=5.43 cm/sec. In Group
      I, 27.8% of patients were in sinus rhythm at 6 months, but had episodes of
      asymptomatic paroxysmal AF lasting >48 hours; all patients were in AF at 12
      months. In Group II, all patients were in sinus rhythm at 12 months. However,
      those patients presenting with a NSWV less but near to 5 cm/sec had frequent
      episodes of asymptomatic paroxysmal AF lasting for <48 hours. CONCLUSION: One
      year after successful direct current cardioversion, TDI analysis at pre
      cardioversion time may be a useful marker to identify a subgroup of patients with
      increased risk for AF recurrence.

PMID- 16948746
TI  - Ventricular fibrillation induced by stretch pulse: implications for sudden death
      due to commotio cordis.
AB  - INTRODUCTION: Nonpenetrating chest wall impact (commotio cordis) may lead to
      sudden cardiac death due to the acute initiation of ventricular fibrillation
      (VF). VF may result from sudden stretch during a vulnerable window, which is
      determined by repolarization inhomogeneity. METHODS: We examined action potential
      morphologies and VF inducibility in response to sudden myocardial stretch in the
      left ventricle (LV). In six Langendorff perfused rabbit hearts, the LV was
      instrumented with a fluid-filled balloon. Increasing volume and pressure pulses
      were applied at different times of the cardiac cycle. Monophasic action
      potentials (MAPs) were recorded simultaneously from five LV epicardial sites.
      Inter-site dispersion of repolarization was calculated in the time and voltage
      domains. RESULTS: Sudden balloon inflation induced VF when pressure pulses of 208
      289 mmHg were applied within a window of 35-88 msec after MAP upstroke, a period
      of intrinsic increase in repolarization dispersion. During the pressure pulse,
      MAPs revealed an additional increase in repolarization dispersion (time domain)
      by 9 +/- 6 msec (P < 0.01). The maximal difference in repolarization levels
      (voltage domain) between sites increased from 19 +/- 3% to 26 +/- 3% (P < 0.05).
      Earliest stretch-induced activation was observed near a site with early
      repolarization, while sites with late repolarization showed delayed activation.
      CONCLUSIONS: Sudden myocardial stretch can elicit VF when it occurs during a
      vulnerable window that is based on repolarization inhomogeneity. Stretch pulses
      applied during this vulnerable window can lead to nonuniform activation.
      Repolarization dispersion might play a crucial role in the occurrence of fatal
      tachyarrhythmias during commotio cordis.

PMID- 16948747
TI  - Unraveling the mystery of commotio cordis.

PMID- 16948748
TI  - Computer model study of electrocardiologic manifestations in asymmetric left
      ventricular hypertrophy.
AB  - Electrocardiologic criteria of left ventricular enlargement do not take into
      consideration the eventuality of asymmetric hypertrophy. Since experimental
      techniques for production of this condition are not available, computer modeling
      was utilized to study its electrocardiologic manifestations. A computer model of
      human ventricles with analytically defined geometry, consisting of 142,000
      elements (1.2 mm spatial resolution), was used to produce models of circumscribed
      hypertrophies by increasing the wall thickness to 150% in various regions of the
      free left ventricular wall, the septum and the apex. Gradients of simulated
      transmembrane action potentials were utilized to compute resultant heart vectors
      at any instant of ventricular activation and recovery, as well as time courses of
      their characteristics and planar projections of vectorgraphic loops. Involvement
      of the septum and/or the anterior wall decreased the maximum QRS vector
      magnitude, an opposite effect resulted from involvement of the lateral and
      posterior wall segments. Directional vector changes predicted the diagnostic
      value of S waves in precordial leads. Asymmetric hypertrophy did not produce
      abnormal Q waves. The maximum T vector increased in hypertrophy of any part of
      the free wall along with an increase of the spatial angle between maximum QRS and
      T vectors. The results of this study may be useful for refinement of
      electrocardiographic and vectorcardiographic diagnostic criteria of asymmetric
      left ventricular hypertrophy.

PMID- 16948749
TI  - Atrioventricular nodal reentrant tachycardia in two siblings with Wolfram
      syndrome.
AB  - This is a case of two siblings with the autosomal recessive Wolfram syndrome who
      both have documented atrioventricular nodal reentrant tachycardia (AVNRT). This
      is the first report to our knowledge that links AVNRT to a syndrome in which the
      putative gene has been identified.

PMID- 16948750
TI  - Image-guided ablation of a ventricular tachycardia originating from the left
      aortic cusp.

PMID- 16948751
TI  - Two LBBB-like tachycardias with identical QRS morphology: what is the mechanism?

PMID- 16948752
TI  - Surgical ablation of atrial fibrillation: the Columbia Presbyterian experience.
AB  - BACKGROUND: The Maze III procedure is an effective surgical treatment for atrial
      fibrillation (AF). However, it is not widely applied due to its complexity,
      increased operative times, and the risk of bleeding. Various energy sources have
      been introduced to simplify the traditional "cut and sew" approach. METHODS: This
      study involves patients undergoing surgical atrial fibrillation ablation (SAFA)
      at a single institution from 1999 to 2005. Type of concomitant procedures,
      preoperative clinical characteristics, and chronicity of AF were evaluated in
      overall patient population. Parameters including surgical approach, lesion
      pattern, and energy source used were collected intraoperatively. Clinical
      outcomes examined were postoperative rhythm success, stroke, early mortality, and
      long-term survival. RESULTS: Three hundred thirty-nine patients were identified.
      Three hundred twenty-eight (96.8%) patients had associated cardiac disease and
      underwent concomitant procedures; 75.8% of patients had persistent AF. Energy
      sources used were microwave (49.8%), radiofrequency (42.2%), and laser (8.0%). In
      41.9% of cases a pulmonary vein encircling lesion was the only lesion created.
      Combination lesion sets were performed in the remaining cases. Rhythm success
      rates at 3, 6, 12, and 24 months were 74.1%, 68.2%, 74.5%, and 71.1%,
      respectively. Patients who underwent surgical removal of left atrial appendage by
      means of stapling or simple excision had no early postoperative stroke. Early
      mortality was 4.9%. Postoperative survival rates at 1, 3, and 5 years were 89.6%,
      83.1%, and 78.0%. CONCLUSIONS: Surgical ablation of atrial fibrillation is a safe
      and effective procedure in restoring sinus rhythm with excellent postoperative
      survival rates. Further advancements in the field will eventually result in
      minimally invasive procedures with higher success rates.

PMID- 16948754
TI  - Would you consider performing an annulus enlargement procedure on your mother?

PMID- 16948753
TI  - Does aortic root enlargement impair the outcome of patients with small aortic
      root?
AB  - BACKGROUND: Posterior root enlargement procedures provide the implantation of
      suitable-sized prosthetic valves in patients with a small aortic root to prevent
      a high postoperative transvalvular gradient. The aim of this study was to
      evaluate long-term results of the posterior root enlargement. METHODS: Between
      1985 and 2002, 124 patients underwent aortic valve replacement with a posterior
      root enlargement. The main indication was a small aortic valve orifice area to
      patient body surface area (indexed valve area < 0.85 cm2/m2). Fifty-four (44%)
      patients were male, and 70 (56%) were female with a mean age 39.1 +/- 14.3 years.
      Indications for operation were severe calcified aortic valve stenosis (37.1%),
      severe aortic insufficiency (25.8%), or combination (37.1%). Seventy-five (60%)
      patients received double-valve replacement. A pericardial patch was used in 100
      patients (80.6%) and a Dacron patch was used in 24 patients. RESULTS: Operative
      mortality was 6.4% (8 patients). The causes of hospital mortality were low
      cardiac output syndrome (LCOS) (in 6 patients), cerebrovascular events (in 1
      patient) and multiple organ failure (in 1 patient). Multivariate analysis
      demonstrated concomitant coronary revascularization to be a significant (p =
      0.03) predictor for early mortality. There were six (5.4%) late deaths. Cox
      proportional hazards regression analysis demonstrated LCOS (p = 0.013) and
      infective endocarditis (p = 0.003) to be significant predictors for late
      mortality. Atrioventricular block required a permanent pacemaker was observed in
      4 patients (3.2%). CONCLUSIONS: Posterior aortic root enlargement techniques can
      be easily applied without additional risks. Long-term survival and freedoms from
      valve-related complications are satisfactory.

PMID- 16948755
TI  - Cardiovascular reoperations in Marfan syndrome.
AB  - BACKGROUND AND AIM OF THE STUDY: The purpose of this study is to analyze the
      outcome results of reoperations in Marfan syndrome patients. METHODS: Between
      1985 and December 2004, 49 patients with Marfan syndrome were operated for aortic
      aneurysms. Of these 49 patients, 9 (18,4%) required > or =1 reoperations after a
      mean duration of 32.2 +/- 26.6 months. The mean duration of follow-up was 52.0 +/
      46.8 months, a total of 39 patient/years. Survival free of reoperation was
      calculated by Cox regression analysis. RESULTS: Surgical indication for operation
      was a chronic aneurysmal dilatation of the ascending or abdominal aorta in seven
      patients (77.8%) and aortic dissection in two (22.2%) at the initial operation.
      In the reoperations, repair of thoracoabdominal aortic aneurysm with separated
      graft interposition in six patients (66.7%), replacement of ascending aorta in
      one (11.1%), replacement of ascending and hemiarchus aorta in one (11.1%), and
      mitral valve replacement in three patients (33.3%) were performed. The hospital
      mortality was 11.1% with one patient. Among the survivors, one expired in the
      follow-up five months after the second operation (12.5%). With the Cox regression
      analysis, survival without reoperation for 13, 24, and 123 months are 95.56 +/-
      3.04%, 90.66 +/- 4.40%, and 60.32 +/- 12.63%, respectively. Mean survival for
      reoperated patients is 99 +/- 14 months (95% confidence interval 72-127 months).
      CONCLUSIONS: Reoperations can be done with low morbidity and mortality. Patients
      should be kept under close follow-up using imaging techniques infinitely.

PMID- 16948756
TI  - Effect of low-dose amiodarone and magnesium combination on atrial fibrillation
      after coronary artery surgery.
AB  - BACKGROUND: To evaluate whether postoperative administration of intravenous low
      dose amiodarone and magnesium sulfate (MgSO(4)) combination would reduce the
      incidence of atrial fibrillation following coronary artery bypass grafting (CABG)
      in normomagnesemic high-risk patients for postoperative atrial fibrillation
      (POAF). METHODS: A total of 136 patients undergoing elective CABG and had > or =3
      risk factors for POAF were prospectively randomized to one of three groups, to
      receive a single dose of amiodarone (5 mg/kg) and MgSO(4) (1.5 g) (combination
      group, n = 44), or an equal dose of amiodarone (amiodarone group, n = 44) or
      equal volumes of saline (control group, n = 48) at early postoperative period.
      Continuous electrocardiographic (ECG) monitoring was performed for the first 48
      hours and an ECG was recorded every 8 hours later. POAF longer than 30 minutes or
      for any length requiring treatment, and the drug-related side effects were
      recorded. RESULTS: The study population showed a homogeneous distribution
      regarding risk factors for POAF and there was no significant difference in
      patient characteristics, echocardiographic variables, or operative variables
      among three groups. POAF developed in 4 patients in combination group, in 16
      patients in amiodarone group and in 16 patients in control group, representing a
      24% relative risk reduction between the combination group and control group (p =
      0.023). No statistically significant difference regarding incidence of POAF was
      observed between amiodarone and control groups. CONCLUSIONS: Combined
      prophylactic therapy with amiodarone and MgSO(4) at the early postoperative
      period without a maintenance phase is an effective, simple, well-tolerated, and
      possibly cost-effective regimen to prevent POAF in normomagnesemic, high-risk
      patients.

PMID- 16948757
TI  - Is preoperative delineation of coronary artery pattern a prerequisite for
      arterial switch operation?
AB  - OBJECTIVE: To determine the effect of preoperative echocardiographic delineation
      of coronary artery pattern on the immediate postoperative result of arterial
      switch procedures. METHODS: A retrospective review of a consecutive series of
      children who underwent the arterial switch operation at a single institution from
      February 2001 to December 2004. RESULTS: Sixty-six children underwent an arterial
      switch operation. The median age at the time of repair was 1.17 months (range 0.2
      96 months). Fifty-five patients (83%) were diagnosed to have dextro-transposition
      of the great arteries, and 11 patients (17%) had double outlet right ventricle of
      the Taussig-Bing type. Associated left-sided obstructive lesions were present in
      12 cases (18.3%). The dominant coronary pattern was 1 LCX; 2R (60.6%), and
      followed by 1L; 2RCX (24.2%). The techniques used for coronary transfer were the
      trapdoor flap, circular buttonhole transfer, or combined technique in all
      patients except for one case. Preoperatively, the coronary artery anatomy was
      adequately delineated in only 26 cases (39.4%). Forty patients (60.6%) had either
      different coronary description or non-documented coronary artery pattern.
      Myocardial ischemia was not observed in any case postoperatively and no patient
      in the series required reoperation for coronary revision. There were 10 in
      hospital deaths (15%) not related to the coronary pattern. Follow-up is available
      for 49 of the surviving patients (87.5%) at a mean of 10.1 months. There has been
      no readmission or reintervention for myocardial ischemia. CONCLUSIONS: The
      trapdoor flap and circular buttonhole techniques are the most practical and
      reproducible maneuvers of coronary transfer during arterial switch operation.
      Both techniques can compensate for inadequate preoperative echocardiographic
      delineation of coronary artery pattern.

PMID- 16948758
TI  - Mid-term angiographic comparison of sequential and individual anastomosis
      techniques for diagonal artery.
AB  - OBJECTIVE: The mid-term patency rates for individual and sequential grafts as
      coronary bypass conduits for diagonal arteries were angiographically compared;
      the impact of native coronary vessel and type of the conduit characteristics are
      investigated. METHODS: Between March 1992 and April 2000, we performed a total
      number of 811 distal anastomosis on diagonal arteries of left anterior descending
      (LAD) artery in 296 patients who underwent coronary artery bypass surgery (CABG)
      distal anastomosis in our clinic. The patients were divided into two groups in
      this prospective study. In group A (n = 195) individual anastomosis technique, in
      group B (n = 101) sequential anastomosis technique was chosen as the myocardial
      revascularization strategy. At an average of 49.4 +/- 13.2 months after coronary
      revascularization procedure coronary angiographies were evaluated. Individual and
      sequential grafting techniques were compared by graft patency rates. RESULTS: The
      patency rates of sequential conduits were markedly higher than those of
      individual conduits (66.7% vs. 89.2%, p = 0.0001). This difference was also clear
      in coronary arteries with poor quality and small (<1.5 mm) diameter (49.1% vs.
      66.6%, p = 0.032). Also, the patency rates of sequential radial artery conduits
      were higher than sequential saphenous vein graft (SVG) conduits (sequential
      radial artery; 94.1%, sequential SVG; 85.3%, p = 0.043). CONCLUSIONS: Sequential
      grafting for diagonal artery is technically more demanding but the mid-term
      results are better than individual grafting especially in coronary arteries with
      poor quality. Using radial artery as a sequential graft increases the mid-term
      graft patency rates.

PMID- 16948759
TI  - Total autologous Ross procedure in a child with aortic root abscess.
AB  - BACKGROUND AND AIM OF THE STUDY: Endocarditis with aortic root abscess is one of
      the most complicated surgical problems. METHODS: An 8-year-old girl presented
      with dyspnea, high fever, and fatigue. She had stenotic bicuspid aortic valve
      with endocarditis and aortic root abscess. Ross procedure was performed with
      fresh autologous pericardial tube and pericardial monocusp valve. Right internal
      mammary artery to right coronary artery bypass was also done due to destroyed
      right coronary artery ostium. RESULTS: Four years after the operation she is in
      excellent clinical condition without medications. Echocardiography reveals mild
      autograft regurgitation and mildly stenotic right ventricular outflow tract.
      CONCLUSIONS: If homografts are not available, total reconstruction of RVOT with
      autologous fresh pericardium may offer reasonable early and mid-term results
      especially when active endocarditis and aortic root abscess is involved.

PMID- 16948760
TI  - Total autologous Ross procedure in a child with aortic root abscess.

PMID- 16948761
TI  - Left atrial myxoma presenting as acute inferior wall infarction-a case report.
AB  - Acute myocardial infarction is a rare form of presentation in patients with left
      atrial myxoma. With wider availability of echocardiography, more and more
      patients with atrial myxomas will be diagnosed. This report describes a patient
      with left atrial myxoma who presented features of acute myocardial infarction and
      had surgical removal of LA myxoma.

PMID- 16948762
TI  - Left atrial myxoma presenting as acute inferior wall infarction--a case report.

PMID- 16948763
TI  - Cardiopulmonary bypass in revascularization and fluid management of exercise
      induced acute myocardial infarction.
AB  - A 52-year-old man was resuscitated from a cardiac arrest during a marathon run.
      During initial evaluation, he received a significant amount of crystalloid fluid
      to maintain end-organ perfusion. Based on electrocardiogram findings, myocardial
      infarction was suspected and an angiogram was performed. An acute thrombosis of
      the left anterior descending vessel was noted, angioplastied, and stented. Given
      that he was in cardiogenic shock, acidotic, and hemodynamically labile, an
      emergent coronary artery bypass grafting with cardiopulmonary bypass was
      performed to simultaneously revascularize the myocardium and remove intravascular
      fluid.

PMID- 16948764
TI  - Confirmed graft flow following use of recombinant factor VIIa in coronary artery
      bypass grafting: a case report and literature review.
AB  - We present our experience of a unique opportunity to survey coronary artery
      bypass graft (CABG) patency following the administration of recombinant factor
      VIIa in the early postoperative period. A review of the published literature on
      use of this medication in cardiothoracic surgery, specifically CABG, is included.

PMID- 16948765
TI  - Combined DOR ventriculoplasty and aortic valve replacement in the treatment of
      post infarction ventricular aneurysm and aortic regurgitation.
AB  - There has been only one other case of endoventricular circular patch plasty
      performed in conjunction with aortic valve replacement reported in the
      literature. We present the unique case of a patient suffering from congestive
      heart failure due to both post-infarct aortic regurgitation and ventricular
      aneurysm along with his successful surgical treatment.

PMID- 16948766
TI  - Mitral valve repair in a patient with Ter Haar Syndrome.
AB  - Ter Haar Syndrome is one of the most deteriorating disorders defined in the
      medical era. Up to date only ten patients were reported. We present a living
      patient with Ter Haar Syndrome who has undergone successful mitral valve repair.

PMID- 16948767
TI  - Chronic expanding intrapericardial hematoma after pericardial paracentesis.
AB  - Chronic expanding intrapericardial hematoma (CEIH) is rare. A thorough search of
      literature revealed a few cases after open heart surgery, chest trauma, or
      epicardial injury. We report the case of a 72-year-old man presenting with a
      large CEIH and constrictive pericarditis, who had no past history of the above
      conditions but had undergone pericardiocentesis four years earlier. The cause of
      the initial hemorrhage of the hematoma might be due to a scratch by a needle
      during pericardial paracentesis. The hematoma had expanded during a course of
      four years. The hematoma was removed surgically, and there has been no sign of
      recurrence 17 months after the operation.

PMID- 16948768
TI  - Surgical treatment of multiple coronary artery fistulas with an associated small
      saccular aneurysm--a case report.
AB  - Coronary angiography (CAG) of a 57-year-old woman with anterior chest discomfort
      revealed no stenosis of the coronary arteries but multiple coronary artery
      fistulas (CAFs). The sites of origin for the CAFs were the right coronary artery,
      left main coronary artery, left anterior descending coronary artery, and
      ascending aorta. The only site for drainage was the main pulmonary artery.
      Furthermore, a small saccular aneurysmal formation was detected. Surgical
      treatment was considered better than conservative treatment or coil embolization,
      and ligation and division of the CAFs were performed during cardiopulmonary
      bypass. Using a Harmonic Scalpel to expose fistulous arteries was very effective.
      CAG performed immediately after surgery demonstrated that all CAFs were repaired.
      The postoperative course was uneventful.

PMID- 16948769
TI  - Cardiopulmonary bypass without ischemic arrest: a myocardial protection strategy
      for high-risk patients requiring urgent CABG.
AB  - For patients requiring emergency coronary artery revascularization, mortality
      remains high. One of the primary reasons is poor functional and metabolic
      recovery of the myocardium after ischemic arrest. We describe a hybrid of the off
      pump and on-pump techniques to avoid ischemic arrest during coronary
      revascularization for this high-risk group.

PMID- 16948770
TI  - Cardiopulmonary bypass without ischemic arrest: a myocardial protection strategy
      for high-risk patients requiring urgent CABG.

PMID- 16948771
TI  - Double-orifice repair for left atrioventricular valve regurgitation in
      atrioventricular septal defect: report of two cases.
AB  - We describe two patients who successfully underwent a surgically created double
      orifice repair using the edge-to-edge repair for residual left atrioventricular
      valve (LAVV) regurgitation in an atrioventricular septal defects (AVSD). Both
      patients had previously received patch closure of the AVSD and partial closure of
      a cleft of the LAVV. Preoperatively, echocardiography showed a wide open cleft
      and remarkable dilatation of the LAVV annulus. Doppler study revealed severe
      regurgitation through the cleft and the central portion of the LAVV orifice and
      no intracardiac shunt. Postoperative echocardiography showed a remarkable
      decrease of the AV valve regurgitation to none or trivial levels without stenosis
      of the LAVV in both patients. Among several valve-sparing techniques, our
      experience suggests that the surgically created double-orifice repair is one of
      the most effective reparative procedures for LAVV regurgitation in AVSD.

PMID- 16948772
TI  - Anomalous coronary artery correction: a minimally invasive approach.

PMID- 16948773
TI  - The role of pannus in the longevity of an Ionescu-Shiley pericardial
      bioprosthesis.
AB  - As the population ages, bioprosthetic heart valves are increasingly being used to
      replace diseased native valves. Bioprosthetic valve durability depends on patient
      age and other factors, but rarely exceeds 15 years. Explanted bioprosthetic
      valves commonly show tissue degeneration, tears, and calcification. Host tissue
      overgrowth (pannus), to the extent of interfering with their function, is another
      finding in bioprostheses that have been in place for long periods. We present a
      case in which a bovine pericardial valve was explanted after more than 20 years
      of implantation. The longevity of this pericardial valve may have been related to
      excessive pannus growth, which most likely protected the valve from earlier
      failure.

PMID- 16948774
TI  - Large left atrial myxoma causing mitral valve obstruction: diagnosis by computed
      tomography.

PMID- 16948777
TI  - Do baseline IL-6 levels predict post-operative morbidity after surgery (CABG) in
      cardiac patients?

PMID- 16948778
TI  - Transient beneficial effects of glutamate-aspartate-enriched cardioplegia on
      ventricular functions in coronary artery bypass grafting.

PMID- 16948779
TI  - Regression of gastroesophageal reflux disease symptoms using dietary
      supplementation with melatonin, vitamins and aminoacids: comparison with
      omeprazole.
AB  - The prevalence of gastroesophageal reflux disease (GERD) is increasing. GERD is a
      chronic disease and its treatment is problematic. It may present with various
      symptoms including heartburn, regurgitation, dysphagia, coughing, hoarseness or
      chest pain. The aim of this study was to investigate if a dietary supplementation
      containing: melatonin, l-tryptophan, vitamin B6, folic acid, vitamin B12,
      methionine and betaine would help patients with GERD, and to compare the
      preparation with 20 mg omeprazole. Melatonin has known inhibitory activities on
      gastric acid secretion and nitric oxide biosynthesis. Nitric oxide has an
      important role in the transient lower esophageal sphincter relaxation (TLESR),
      which is a major mechanism of reflux in patients with GERD. Others biocompounds
      of the formula display anti-inflammatory and analgesic effects. A single blind
      randomized study was performed in which 176 patients underwent treatment using
      the supplement cited above (group A) and 175 received treatment of 20 mg
      omeprazole (group B). Symptoms were recorded in a diary and changes in severity
      of symptoms noted. All patients of the group A (100%) reported a complete
      regression of symptoms after 40 days of treatment. On the other hand, 115
      subjects (65.7%) of the omeprazole reported regression of symptoms in the same
      period. There was statiscally significant difference between the groups (P <
      0.05). This formulation promotes regression of GERD symptoms with no significant
      side effects.

PMID- 16948780
TI  - Lipid-protein modifications during ascorbate-Fe2+ peroxidation of photoreceptor
      membranes: protective effect of melatonin.
AB  - The rod outer segment (ROSg) membranes are essentially lipoprotein complexes.
      Rhodopsin, the major integral protein of ROSg, is surrounded by phospholipids
      highly enriched in docosahexaenoic acid (22:6 n3). This fluid environment plays
      an important role for conformational changes after photo-activation. Thus, ROSg
      membranes are highly susceptible to oxidative damage. Melatonin synthesized in
      the pineal gland, retina and other tissues is a free radical scavenger. The
      principal aim of this work was to study the changes in the ROSg membranes
      isolated from bovine retina submitted to nonenzymatic lipid peroxidation
      (ascorbate-Fe2+ induced), during different time intervals (0-180 min). Oxidative
      stress was monitored by increase in the chemiluminescence and fatty acid
      alterations. In addition we studied the in vitro protective effect of 5 mm
      melatonin. The total cpm originated from light emission (chemiluminescence) was
      found to be lower in those membranes incubated in the presence of melatonin. The
      docosahexaenoic acid content decreased considerably when the membranes were
      exposed to oxidative damage. This reduction was from 35.5 +/- 2.9% in the native
      membranes to 12.65 +/- 1.86% in those peroxidized during 180 min. In the presence
      of 5 mm melatonin we observed a content preservation of 22:6 n3 (23.85 +/- 2.77%)
      at the same time of peroxidation. Simultaneously the alterations of membrane
      proteins under oxidative stress were studied using sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). Loss of protein sulfhydryl groups
      and increased incorporation of carbonyl groups were utilized as biomarkers of
      protein oxidation. In membranes exposed to Fe2+ -ascorbate, we observed a
      decrease of protein thiols from 50.9 +/- 3.38 in native membranes to 1.72 +/-
      2.81 nmol/mg of protein after 180 min of lipid peroxidation associated with
      increased incorporation of carbonyl groups into proteins from 7.20 +/- 2.50 to
      12.50 +/- 1.12 nmol/mg of protein. In the SDS-PAGE we observed a decrease in the
      content of all the proteins, mainly rhodopsin, as a consequence of peroxidation.
      Melatonin, prevent both lipid peroxidation and protein oxidation.

PMID- 16948781
TI  - Mechanisms of protection by melatonin against acetaminophen-induced liver injury
      in mice.
AB  - The present study was performed to determine whether melatonin protects mouse
      liver against severe damage induced by acetaminophen (APAP) administration and
      where melatonin primarily functions in the metabolic pathway of APAP to protect
      mouse liver against APAP-induced injury. Treatment of mice with melatonin (50 or
      100 mg/kg, p.o.) 8 or 4 hr before APAP administration (750 mg/kg, p.o.)
      suppressed the increase in plasma alanine aminotransferase and aspartate
      aminotransferase activities in a dose- and a time-dependent manner. Melatonin
      treatment (100 mg/kg, p.o.) 4 hr before APAP administration remarkably inhibited
      centrilobular hepatic necrosis with inflammatory cell infiltration and increases
      in hepatic lipid peroxidation and myeloperoxidase activity, an index of tissue
      neutrophil infiltration, as well as release of nitric oxide and interleukin-6
      into blood circulation at 9 hr after APAP administration. However, melatonin
      neither affected hepatic reduced glutathione (GSH) content nor spared hepatic GSH
      consumption by APAP treatment. Moreover, pretreatment with melatonin 4 hr before
      APAP administration did not influence the induction of hepatic heat shock protein
      70 (HSP70) by APAP and melatonin alone did not induce HSP70 in mouse liver. These
      results indicate that exogenously administered melatonin exhibits a potent
      hepatoprotective effect against APAP-induced hepatic damage probably downstream
      of the activity of cytochrome P450 2E1, which works upstream of GSH conjugation
      in the pathway of APAP metabolism, via its anti-nitrosative and anti-inflammatory
      activities in addition to its antioxidant activity.

PMID- 16948782
TI  - Melatonin prevents neutrophil-mediated oxidative injury in Escherichia coli
      induced pyelonephritis in rats.
AB  - Regarding the mechanisms of renal scarring in pyelonephritis, several hypotheses
      have been put forward, among which oxidative stress is prominent. The present
      study investigated the possible protective effect of melatonin treatment against
      Escherichia coli-induced oxidative injury and scarring in renal tissue. For this
      purpose, 0.1 mL E. coli (ATCC 25922; 10(10) colony-forming units/mL) or saline
      was injected directly into the renal parenchyma of Wistar rats. Pyelonephritic
      rats were treated with either saline or melatonin (10 mg/kg) intraperitoneally.
      Twenty-four hours or 1 wk after E. Coli injection, rats were decapitated and
      trunk blood samples were collected for BUN, creatinine, tumor necrosis factor
      alpha (TNF-alpha) and lactate dehydrogenase (LDH) determination. In kidney
      samples, histological analysis was performed, and malondialdehyde (MDA),
      glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents
      were measured. Formation of reactive oxygen species was monitored using a
      chemiluminescence (CL) technique. Escherichia Coli inoculation caused a
      significant reduction in renal GSH levels, which was accompanied by significant
      increases in MDA levels, MPO activity, CL levels and collagen content of the
      renal tissues (P < 0.05-0.001). Similarly, serum TNF-alpha and, LDH, BUN and
      creatinine levels were elevated in the pyelonephritic rats when compared with
      control animals. Melatonin treatment reversed all these biochemical indices, as
      well as histopathological alterations induced by acute pyelonephritis. The
      protective effects of melatonin can be ascribed to its ability to inhibit
      neutrophil infiltration, to balance the oxidant-antioxidant status, and to
      regulate the generation of inflammatory mediators, suggesting a future role for
      melatonin in the treatment of acute pyelonephritis.

PMID- 16948783
TI  - Effects of combination of melatonin and dexamethasone on acute lung injury in a
      mice model of carrageenan-induced pleurisy.
AB  - The aim of this study was to investigate the effects of combination therapy with
      melatonin and dexamethasone (DEX) on acute lung injury. In particular, we
      investigated the effects of combination therapy in animal models of acute lung
      inflammation (carrageenan-induced pleurisy). Injection of carrageenan into the
      pleural cavity of rats elicited an acute inflammatory response characterized by
      fluid accumulation in the pleural cavity which contained a large number of
      neutrophils [polymorphonuclear leukocyte (PMN)] as well as an infiltration of PMN
      in lung tissues and subsequent lipid peroxidation, and increased production of
      nitrite/nitrate (NOx), and prostaglandin E2 (PGE2). Furthermore, carrageenan
      induced an upregulation of the adhesion molecules ICAM-1 and P-selectin,
      inducible nitric oxide synthase, cycloxygenase-2 as well as nitrotyrosine as
      determined by immunohistochemical analysis of lung tissues. No anti-inflammatory
      effect was observed in animals treated with melatonin (10 mg/kg) or with DEX
      (0.01 mg/kg) alone. This study shows that the combination therapy with melatonin
      and DEX reduced the degree of acute lung inflammation and tissue damage
      associated with carrageenan-induced pleurisy in mice and supports the possible
      use of melatonin in combination with steroids in order to reduce the dose and the
      side effects related with the use of steroids for the management of inflammatory
      disease.

PMID- 16948784
TI  - In vivo protective effect of melatonin on cadmium-induced changes in redox
      balance and gene expression in rat hypothalamus and anterior pituitary.
AB  - Cadmium (Cd) is widely used in industrial applications and is an important side
      contaminant of agricultural products. As an endocrine disruptor, Cd modifies
      pituitary hormone release. It has been shown that this metal causes oxidative
      stress in primary cultures of anterior pituitary cells. To examine whether Cd
      induces redox damage in the hypothalamic-pituitary axis in vivo and to evaluate
      the efficacy of the antioxidant molecule melatonin to prevent Cd activity, rats
      were exposed to Cd (5 p.p.m. in drinking water) with or without melatonin (3
      microg/mL drinking water) for 1 month. In the anterior pituitary, Cd increased
      lipid peroxidation and mRNA levels for heme oxygenase-1 (HO-1) at both time
      intervals tested (09:00 and 01:00 hr, beginning of rest span and middle of
      activity span, respectively). Melatonin administration prevented the Cd-induced
      increase in both parameters. In the hypothalamus, Cd affected the levels of mRNA
      for HO-1 by decreasing it in the evening. Melatonin reduced hypothalamic HO-1
      gene expression. Cd treatment augmented gene expression of nitric oxide synthase
      (NOS)1 and NOS2 in the pituitary whereas melatonin decreased it, impairing the
      activity of Cd. Exposure to Cd increased the levels of hypothalamic NOS1 mRNA at
      09:00 hr and decreased the levels of NOS2 mRNA at 01:00 hr, with melatonin
      treatment preventing Cd effects. Cd treatment decreased plasma thyroid
      stimulating hormone levels at both examined times, while melatonin reversed the
      effect of Cd at 09:00 hr and partially counteracted the effect at 01:00 hr. There
      were important variations between day and night in the expression of all the
      genes tested in both tissues. Melatonin treatment was effective reducing all
      examined effects of Cd, documenting its effectiveness to protect the rat
      hypothalamic-pituitary axis from the toxic metal effects.

PMID- 16948785
TI  - LIM homeodomain proteins Islet-1 and Lim-3 expressions in the developing pineal
      gland of chick embryo by immunohistochemistry.
AB  - LIM homeodomain proteins Islet-1 and Lim-3 expression and their role in nervous
      tissue and endocrine glands have been reported; however, nothing is known
      concerning Islet-1 and Lim-3 expression in the developing pineal gland of the
      chick embryo. The aim of the present study was to determine the ontogeny of Islet
      1 and Lim-3 expression in the developing pineal gland of chick embryo using
      immunohistochemistry. The results showed that Islet-1 and Lim-3 immunopositive
      cells were first detected in the pineal evagination of chick embryos at day 4
      (E4) and E4.5 of incubation, respectively. In the later developing stages, both
      Islet-1 and Lim-3 immunopositive cells were consistently detected in the
      follicular and parafollicular pinealocytes throughout the pineal gland. The
      relative percentage of Islet-1 immunopositive (Islet-1+) cells relative to the
      total cells was about 6% at E4.5, and then kept increasing (P < 0.05) and reached
      about 40% by E12.5; this was followed by no obvious changes until the chicks were
      newly hatched. The change in Lim-3 immunopositive (Lim-3+) cell number was
      parallel to that of Islet-1, although Lim-3+ cell were significantly fewer than
      Islet-1+ cell numbers from E4.5 to E8.5 (P < 0.05). Dual immunohistochemical
      staining results showed that almost all the Lim-3+ cells expressed Islet-1 at
      every stage examined, and about 90% of Islet-1+ cells were proliferating cell
      nuclear antigen negative. These results suggest that both Islet-1 and Lim-3 may
      be involved in regulating the development and functional maturation of the pineal
      gland, although further studies are required in elucidating the functional roles
      of Islet-1 and Lim-3 and the related mechanisms.

PMID- 16948786
TI  - Melatonin reduces ischemia/reperfusion-induced superoxide generation in arterial
      wall and cell death in skeletal muscle.
AB  - The purpose of this study was to determine the effect of melatonin on superoxide
      generation in arterial wall at an early phase of reperfusion and on endothelial
      dysfunction of microvasculature and cell viability of cremaster muscle at late
      phase of reperfusion (24 hr) after prolonged ischemia. Bilateral vascular
      pedicles which supply blood flow to the cremaster muscle were exposed. After
      surgical preparation, microvascular clamps were applied on the right iliac,
      femoral and spermatic arteries to create 4 hr of ischemia in both feeding vessels
      and the unexposed cremaster muscle. The vascular clamping was omitted on the left
      iliac, femoral and spermatic arteries and served as an internal control.
      Melatonin or Vehicle was via by intravenous injection at 10 min prior to
      reperfusion and 10 min after reperfusion. In the first experiment, the vascular
      pedicle was harvested after reperfusion to measure superoxide generation in real
      time by lucigenin-derived chemiluminescence. In the second experiment,
      endothelial-dependent and -independent vasodilatation was examined in the
      terminal arteriole of cremaster muscle which was then harvested to examine cell
      viability by WST-1 assay on day 2. Superoxide generation in arterial wall peaked
      at first 5-min of reperfusion and declined to near baseline after 60 min of
      reperfusion. Melatonin treatment significantly reduced superoxide generation in
      arterial walls and improved cell viability in cremaster muscles. Melatonin
      treatment also significantly reduced microvascular endothelial dysfunction which
      was still observable in the microcirculation of cremaster muscle after 24 hr of
      reperfusion. Melatonin reduces superoxide generation in the early phase of
      reperfusion resulting in attenuating endothelial dysfunction and muscle cell
      death in the late phase of reperfusion.

PMID- 16948787
TI  - Effect of photoperiod on the fish innate immune system: a link between fish
      pineal gland and the immune system.
AB  - The pineal gland via its secretory product, melatonin, influences the light-dark
      rhythm in most vertebrates including fish. Apart from the information concerning
      this circadian rhythm, the interrelation of the melatonin with other
      physiological processes has not been considered in fish. Thus, we evaluated the
      changes in the humoral innate immune system of seabream (Sparus aurata L.) and
      sea bass (Dicentrarchus labrax L.) specimens exposed to a constant light-dark
      photoperiod (12 hr L:12 hr D). Serum was obtained from blood samples collected at
      02:00, 08:00 hr (light-on), 14:00, 20:00 hr (light-off) and at 08:00 hr again.
      Among the humoral innate immune responses, complement, lysozyme and peroxidase
      activities were determined. Complement activity was higher during the day than
      during the night in both fish species. Seabream lysozyme activity reached its
      maximum at 20:00 and 02:00 hr but was hardly affected in sea bass. Finally, the
      peroxidase activity of seabream was significantly higher at 08:00 hr than during
      the rest of the cycle while, in sea bass, it showed little variation. The present
      results demonstrate that the humoral innate immune system has a circadian rhythm
      based on the light-dark cycle and that this cycle might be affected by the pineal
      gland.

PMID- 16948788
TI  - Melatonin inhibits endothelial nitric oxide production in vitro.
AB  - Endothelial cell function is a major player on the regulation of both vascular
      tonus and permeability. Activation of nitric oxide synthase (NOS) by bradykinin
      is one physiological pathway for the well-known vascular relaxation mediated by
      endothelial-derived nitric oxide (NO). In this study we investigated if
      melatonin, which is known to modulate endothelial cell function and NO production
      in other tissues, is able to impair bradykinin-induced NO production in vitro.
      Rat microvascular endothelial cells were incubated with fluorescent dyes to
      detect either NO or Ca2+. In addition, cGMP levels were measured by enzyme
      immunoassay. We found that while bradykinin (1-100 nm) increased both cytosolic
      Ca2+ and NO production, melatonin (1 nm) abolished this NO production but not
      cytosolic Ca2+ elevation. N-acetylserotonin (0.1 and 1 nm) had the same effect,
      while the selective agonist for MT3 receptors (5-MCA-NAT, 1 nm) had no effect.
      Moreover, nonselective and MT2-selective antagonists did not alter the effect of
      melatonin, suggesting that it is not mediated by MT melatonin receptors. A
      possible direct inhibition of calmodulin was also discarded as melatonin did not
      mimic the effect of calmidazolium on cytosolic Ca2+. Melatonin also abolished
      cGMP production induced by 1 microm bradykinin, indicating that the NO downstream
      effect is impaired. Thus, here we show that melatonin reduces NO production
      induced by bradykinin by a mechanism upstream to the interaction of Ca2+ 
      calmodulin with NOS. Moreover, this effect might be the basis of the diurnal
      variation in endothelial cell function.

PMID- 16948789
TI  - Melatonin prevents H2O2-induced activation of rat hepatic stellate cells.
AB  - Considerable evidence shows therapeutic effects of melatonin on liver injury and
      the involvement of hepatic stellate cells (HSCs) in vivo. In the present studies,
      we investigate the protective effect of melatonin on H2O2-induced activation of
      HSCs in vitro. Compared with that in control HSCs, synthesis of collagen type I
      was increased in H2O2-treated cells. Melatonin pretreatment significantly
      inhibited the above effects of H2O2 in HSCs. CCAAT/enhancer-binding protein alpha
      (C/EBP-alpha), which could partially reverse the phenotype of activated HSCs,
      augmented in HSCs pretreated with melatonin. Moreover, secretion of the most
      important fibrotic cytokine transforming growth factor beta 1 (TGF-beta1)
      diminished in melatonin-pretreated HSCs. These results suggest that melatonin
      prevents H2O2-induced activation of HSCs and that the mechanism involves, at
      least in part, differential regulation of TGF-beta1 and C/EBP-alpha gene
      expression.

PMID- 16948790
TI  - Seasonality of psychopathology and circannual melatonin rhythm.
AB  - The association of seasonal changes in health and disease has been known for
      centuries. The prevalence of psychopathological symptoms with seasonal
      fluctuations and the use of melatonin as a biological marker of circadian and
      circannual rhythms is well documented. The aim of this work was to study the
      variability of melatonin secretion between summer and winter in our geographical
      area (28 degrees N, 16 degrees W) and relate the changes to the level of
      psychopathology. Ten drug-free, nonsmoker, healthy subjects were studied in
      summer (August) and winter (December). Blood samples for melatonin assays were
      collected every hour at night for 5 hr, from 22:00 to 02:00 hr, and next day at
      noon. Melatonin was assayed by an ELISA technique. Psychopathology was evaluated
      by means of the 28-item version of the General Health Questionnaire (GHQ-28). All
      subjects had a circadian rhythm of melatonin secretion in summer and winter.
      There was a seasonal rhythm with melatonin levels being significantly higher at
      night in winter than in summer. Melatonin levels at 22:00, 23:00, 24:00 and 01:00
      hr and mean melatonin area under the curve (AUC) were significantly higher in
      winter than in summer. Melatonin AUC increased 80% in winter compared with
      summer. The GHQ-28 somatic and anxiety subscales and the total GHQ-28 score were
      significantly higher in winter than summer. Psychopathology scores were
      significantly and negatively correlated with melatonin production in summer and
      winter. Our data strongly suggest that melatonin production and psychopathology
      levels present seasonal fluctuations and these variations should be taken into
      account when conducting research in this field.

PMID- 16948791
TI  - A melatonin-rich germplasm line of St John's wort (Hypericum perforatum L.).
AB  - The objective of this study was to evaluate the possibility of selecting genetic
      variants of plants with enhanced concentrations of the indoleamine melatonin. A
      germplasm line of the medicinal plant species, St John's wort (Hypericum
      perforatum L.), with high levels of melatonin was selected in vitro using
      mutagenized tissues. The germplasm line has remained stable over a 5-yr period
      and contained >12-fold (1200%) melatonin content compared with the wild-type
      plant. Melatonin is a ubiquitous, highly conserved molecule with known
      therapeutic roles in the treatment of sleep disorders, depression, aging,
      inhibition of cancer cell growth and as a free radical scavenger and antioxidant.
      The selected melatonin-rich germplasm line of St John's wort may facilitate
      fundamental studies on melatonin biosynthesis, metabolism and new developments in
      natural products for treatment of human diseases.

PMID- 16948792
TI  - Beneficial effects of melatonin in protecting against cyclosporine A-induced
      cardiotoxicity are receptor mediated.
AB  - Melatonin, the chief product secreted by pineal gland, is capable of reducing
      free radical damage by acting directly as a free radical scavenger, and
      indirectly, by stimulating of antioxidant enzymes. Cyclosporine A (CsA) is the
      most widely used immunosuppressive drug, but its therapeutic use has several side
      effects including, i.e. nephrotoxicity and cardiotoxicity. This study was
      designed to examine the beneficial effects of melatonin in preventing CsA-induced
      cardiotoxicity. Additionally, we investigated the ability of melatonin to protect
      the rat heart via melatonin receptor. In one group of Wistar rats, melatonin (1
      mg/kg/day i.p.) was administered concurrently with CsA (15 mg/kg/day s.c.) for 21
      days. In another group of animals, melatonin was injected with CsA and luzindole,
      an antagonist of melatonin receptors. Oxidative stress in heart tissue
      homogenates was estimated using thiobarbituric acid reactive substances (TBARS),
      reduced glutathione levels and antioxidant enzyme activities including catalase
      and superoxide dismutase. CsA administration for 21 days produced elevated levels
      of TBARS, marked depletion of cardiac antioxidant enzymes and caused
      morphological alterations in myocardial fibers. Melatonin markedly reduced TBARS
      levels, increased the antioxidant enzyme levels and normalized altered cardiac
      morphology. The protective effects of melatonin were lost when the animals
      received the melatonin receptor antagonist. In conclusion our study shows that,
      (a) melatonin significantly reduces CsA cardiotoxicity, and (b) the reduction in
      CsA-induced cardiotoxicity was mediated by the binding of melatonin to its
      membrane receptors.

PMID- 16948795
TI  - Atrophy and hypertrophy of skeletal muscles: structural and functional aspects.
AB  - This review summarizes current information on structural and functional changes
      that occur during muscle atrophy and hypertrophy. Most published studies consider
      an increase in total mass of a muscle as hypertrophy, whereas a decrease in total
      mass of a muscle is referred to as atrophy. In hypertrophy, the rate of synthesis
      is much higher than the rate of degradation of muscle contractile proteins,
      leading to an increase in the size or volume of an organ due to enlargement of
      existing cells. When a muscle remains in disuse for a long period, the rate of
      degradation of contractile proteins becomes greater than the rate of replacement,
      resulting in muscle atrophy. This defect may occur as a result of lack of
      nutrition, loss of nerve supply, micro-gravity, ageing, systemic disease,
      prolonged immobilization or disuse. An understanding of the specific
      modifications that occur during muscle atrophy and hypertrophy may facilitate the
      development of novel techniques, as well as new therapies for affected muscles.

PMID- 16948797
TI  - Adventitia-dependent mechanical properties of brachiocephalic ovine arteries in
      in vivo and in vitro studies.
AB  - AIM: An adventitia dependent regulation of the vascular smooth muscle tone has
      been described. However, if the adventitia plays an active role on arterial wall
      biomechanical behaviour and functions remains to be established. Our aim was to
      characterize the influence of adventitia on arterial wall mechanical properties
      and the arterial conduit and buffer functions. METHODS: Ovine brachiocephalic
      arteries were studied in vivo (n = 8) and in vitro (with null tone) in a
      circulation mock (n = 8). Isobaric, isoflow and isofrequency studies were
      performed. In each segment, pressure and diameter waves were assessed before and
      after adventitia removal. From the arterial stress-strain relationship, we
      derived the elastic and the viscous modulus. The buffering and conduit functions
      were calculated using the Kelvin-Voigt's time constant and the inverse of the
      characteristic impedance, respectively. RESULTS: In in vivo studies arterial
      diameter decreased after adventitia removal (P < 0.05). Elastic and viscous
      modulus in in vivo studies were significantly higher in adventitia-removed
      arteries, compared with values in intact vessels (P < 0.05). This behaviour was
      not observed in in vitro experiments. An impairment of buffer and conduit
      functions was observed in vivo after adventitia removal (P < 0.05), while both
      functions remain unchanged in in vitro studies (P > 0.05). CONCLUSIONS: Arterial
      wall viscosity and elasticity were influenced by adventitia removal in in vivo
      studies, possibly by a smooth muscle-dependent mechanism, since it was not
      present in in vitro experiments. Adventitia would be involved in a physiological
      mechanism of arterial wall viscous and elastic properties regulation, that could
      influence arterial buffering and conduit functions.

PMID- 16948796
TI  - Forearm plethysmography in the assessment of vascular tone and resistance
      vasculature design: new methodological insights.
AB  - AIM: High peripheral resistance and structural alteration in resistance arteries
      are central phenomena in essential hypertension and have been widely examined by
      forearm venous occlusion plethysmography; at rest for studying vascular tone, and
      during reactive hyperaemia for studying vascular structure. This work concerns
      the influence of venous pressure on hyperaemic vascular resistance (Rmin), the
      reproducibility of hyperaemic and resting vascular resistances (Rrest) and the
      relation between forearm and total peripheral vascular resistance (TPR). METHODS:
      In four healthy subjects, intravenous and intra-arterial blood pressures were
      measured simultaneously with plethysmographic recordings of hyperaemic and
      resting forearm blood flows. Reproducibility was examined in 15 young and 14
      middle-aged healthy subjects and in 21 untreated hypertensive patients. RESULTS:
      Rmin remained low in the first recorded cardiac cycle, but rose in the second,
      even though corrected for the venous pressure rise, suggesting vascular tone
      recovery along with venous congestion. Between-day reproducibility of Rmin was
      high in middle-aged normotensive (8.7%) and hypertensive subjects (10.6%), but
      Rmin fell significantly between successive days in the young subjects. Rrest
      correlated with TPR, but required up to 40 min to reach steady state and showed
      high day-to-day variation in young (21.8%) and hypertensive subjects (16.2%).
      CONCLUSIONS: During hyperaemia, vascular resistance should be measured in the
      first cardiac cycle following venous occlusion to minimize influences of venous
      pressure rise and possible tone recovery. Rrest seems to reflect TPR. About 20
      subjects may be needed to detect 15% changes between days in Rrest, fewer when
      concerning Rmin and TPR.

PMID- 16948798
TI  - Soleus, plantaris and gastrocnemius VEGF mRNA responses to hypoxia and exercise
      are preserved in aged compared with young female C57BL/6 mice.
AB  - AIMS: In humans, skeletal muscle capillarization and the vascular endothelial
      growth factor (VEGF) mRNA response to acute exercise are lower in aged compared
      with young. The exercise-induced increase in VEGF mRNA has been proposed to
      involve hypoxic regulation of VEGF and is believed to be fibre type-dependent. We
      hypothesized that attenuated VEGF mRNA responses to hypoxia and exercise with
      advanced age would be greatest in oxidative vs. glycolytic muscles. METHODS: 3-
      and 24-month-old female C57BL/6 mice were exposed to acute hypoxia (FI O2 = 0.06)
      or performed a single exercise (65% of maximum treadmill running speed) bout.
      Capillarization and VEGF mRNA were analysed in the soleus, plantaris and
      gastrocnemius muscles. RESULTS: In each muscle, VEGF mRNA was greater in aged
      compared with young, while the VEGF mRNA response to acute hypoxia or acute
      exercise was similar between young and aged. Morphological analysis revealed that
      type IIA fibre percentage and type IIB capillarization in the plantaris were
      greater and type IIB fibre cross-sectional area (FCSA) in the gastrocnemius was
      smaller in aged compared with young. CONCLUSIONS: These findings suggest that
      ageing does not impair the potential for non-pathological angiogenesis in mice
      and that acute exercise increases VEGF mRNA in the soleus, plantaris and
      gastrocnemius muscles, which differ considerably in fibre type percentage.

PMID- 16948799
TI  - Relationship between systemic nitric oxide metabolites and cyclic GMP in healthy
      male volunteers.
AB  - AIM: Nitric oxide (NO) is an endogenous mediator of many physiological processes,
      many of which are mediated by cyclic guanosine 3',5'-monophosphate (cGMP). Much
      effort has been made to validate clinical markers of NO production or
      bioavailability. While the measurement of plasma nitrate, nitrite, and cGMP
      concentrations have been suggested to reflect endogenous production of NO, there
      is no study showing whether there is correlation between these three markers. In
      the present study, we investigate whether there is correlation between the plasma
      concentrations of nitrate, nitrite, and cGMP in a relatively homogeneous group of
      141 healthy subjects. METHODS: Venous blood samples were collected from healthy
      male subjects and plasma aliquots were then immediately removed and stored at -70
      degrees C until analysed in duplicate for their nitrite and nitrate content using
      ozone-based chemiluminescence assays. Plasma cGMP levels were determined by using
      a commercial enzyme immunoassay. RESULTS: While we found no significant
      correlation between plasma nitrite and nitrate concentrations (P = 0.747), or
      between plasma nitrate and cGMP concentrations (P = 0.221), a significant
      positive correlation was found between plasma cGMP and nitrite concentrations (P
      = 0.017, r(s) = 0.270). CONCLUSIONS: The significant correlation we found between
      plasma nitrite and cGMP concentrations is consistent with the notion that nitrite
      or cGMP concentrations in plasma may be useful clinical markers of NO formation
      in healthy subjects.

PMID- 16948800
TI  - Systemic effects of angiotensin III in conscious dogs during acute double
      blockade of the renin-angiotensin-aldosterone-system.
AB  - AIMS: The study was designed to determine (i) whether the effects of angiotensin
      III (AngIII) are similar to those of angiotensin II (AngII) at identical plasma
      concentrations and (ii) whether AngIII operates solely through AT1- receptors.
      METHODS: Angiotensin II (3 pmol kg(-1) min(-1)-3.1 ng kg(-1) min(-1)) or AngIII
      (15 pmol kg(-1) min(-1)-14 ng kg(-1) min(-1)) was infused i.v. during acute
      inhibition of angiotensin converting enzyme (enalaprilate; 2 mg kg(-1)) and of
      aldosterone (canrenoate; 6 mg kg(-1) plus 1 mg kg(-1) h(-1)). Arterial plasma
      concentrations of angiotensins were determined by radioimmunoassay using a cross
      reacting antibody to AngII. During ongoing peptide infusion, candesartan (2 mg
      kg(-1)) was administered to block the AT1-receptors. RESULTS: Angiotensin
      immunoactivity in plasma increased to 60 +/- 10 pg mL(-1) during infusion of
      AngII or infusion of AngIII. AngII significantly increased mean arterial blood
      pressure (+14 +/- 4 mmHg) and plasma aldosterone by 79% (+149 +/- 17 pg mL(-1))
      and reduced plasma renin activity and sodium excretion (-41 +/- 16 mIU L(-1) and 
      46 +/- 6 micromol min(-1) respectively). AngIII mimicked these effects and the
      magnitude of AngIII responses was statistically indistinguishable from those of
      AngII. All measured effects of both peptides were blocked by candesartan.
      CONCLUSION: At the present arterial plasma concentrations, AngIII is equipotent
      to AngII with regard to effects on blood pressure, aldosterone secretion and
      renal functions, and these AngIII effects are mediated through AT1- receptors.
      The metabolic clearance rate of AngIII is five times that of AngII.

PMID- 16948801
TI  - New method for evaluation of lung lymph flow rate with intact lymphatics in
      anaesthetized sheep.
AB  - AIM: Lung lymph has commonly been studied using a lymph fistula created by tube
      cannulation into the efferent duct of the caudal mediastinal node in sheep. In
      this method, the tail region of the caudal mediastinal node is resected and the
      diaphragm is cauterized to exclude systemic lymph contamination, and cannulation
      is performed into one of the multiple efferent ducts originating from the caudal
      mediastinal node. Moreover, the pumping activity of lymphatics might be
      diminished by cannulation. Therefore, the purpose of the study was to evaluate
      the flow rate of lung lymph with maintenance of intact lymphatic networks around
      the caudal mediastinal node to the thoracic duct in sheep. METHODS: An ultrasound
      transit-time flow meter was used to measure lung lymph flow. The thoracic duct
      was clamped just above the diaphragm and the flow probe was attached to the
      thoracic duct just after the last junction with an efferent duct from the caudal
      mediastinal node. The lung lymph flow rate was measured at baseline and under
      conditions of lung-oedema formation. RESULTS: The baseline lung lymph flow rate
      in our model was three- to sixfold greater than values obtained with the
      cannulation method. With oedema-formation, the lung lymph flow rate was the same
      as that measured using cannulation. CONCLUSION: The lung lymph flow was
      unexpectedly large under the conditions of the study, and our data suggest that
      the drainage effect of lymphatics is significant as a safety factor against
      pulmonary oedema formation.

PMID- 16948802
TI  - Review article: gastrointestinal bleeding with low-dose aspirin - what's the
      risk?
AB  - This review examines ulcers and gastrointestinal bleeding with low-dose aspirin,
      focusing on randomized placebo-controlled trials. The single endoscopic trial
      assessing ulcers showed no significant difference in 12-week ulcer incidence: 6%
      of 381 given placebo vs. 7% of 387 given 81 mg enteric-coated aspirin. The
      relative risk of major gastrointestinal bleeding with low-dose aspirin in a meta
      analysis of placebo-controlled trials of vascular protection was 2.07 (95% CI:
      1.61-2.66). The absolute rate increase with aspirin above placebo was 0.12% per
      year (95% CI: 0.07-0.19%) with a number-needed-to-harm of 833 patients (95% CI:
      526-1429). A meta-analysis of aspirin 50-1500 mg daily reported an odds ratio for
      any gastrointestinal bleeding of 1.68 (95% CI: 1.51-1.88) with an number-needed
      to-harm at 1 year of 247. The relative risk of hospitalization for upper
      gastrointestinal bleeding with low-dose aspirin in a large Danish cohort study
      was 2.6 (95% CI: 2.2-2.9) with an absolute annual incidence of 0.6%. Factors that
      may increase the risk of gastrointestinal bleeding include prior history of
      ulcers or gastrointestinal bleeding, corticosteroid use, anticoagulant therapy
      and addition of a non-aspirin non-steroidal anti-inflammatory drug. When
      determining whether low-dose aspirin is appropriate for an individual patient,
      the cardiovascular benefit must be weighed against the potential for clinical
      events such as gastrointestinal bleeding.

PMID- 16948803
TI  - Review article: the management of achalasia - a comparison of different treatment
      modalities.
AB  - BACKGROUND: Achalasia is an uncommon primary oesophageal motor disorder with an
      unknown aetiology. Therapeutic options for achalasia are aimed at decreasing the
      lower oesophageal sphincter pressure, improving the oesophageal empting, and most
      importantly, relieving the symptoms of achalasia. Modalities for treatment
      include pharmacologic, endoscopic, pneumatic dilatation and surgical. The
      decision of which modality to use involves the consideration of multiple clinical
      and economic factors. AIM: To review the management strategies currently
      available for achalasia. METHODS: A Medline search identified the original
      articles and reviews the published in the English language literature between
      1966 and 2006. RESULTS: The results reveal that pharmacotherapy, injection of
      botulinum toxin, pneumatic dilatation and minimally invasive surgical
      oesophagomyotomy are variably effective at controlling the symptoms of achalasia
      but that each modality has specific strengths and weaknesses which make them each
      suitable in certain populations. Overall, pharmacologic therapy results in the
      shortest lived, least durable response followed by botulinum toxin injection,
      pneumatic dilatation and surgery, respectively. CONCLUSION: The optimal treatment
      for achalasia remains an area of controversy given our lack of complete
      understanding about the pathophysiology of the disease as well as the high
      numbers of clinical relapse after treatment. Further research focusing on optimal
      dosing of botulinum toxin injection and optimal timing of repeated graduated
      pneumatic dilatations could add to our knowledge regarding long-term therapy.

PMID- 16948804
TI  - Review article: modulation of the brain-gut axis as a therapeutic approach in
      gastrointestinal disease.
AB  - BACKGROUND: The importance of bi-directional brain-gut interactions in
      gastrointestinal illness is increasingly being recognized, most prominently in
      the area of functional gastrointestinal disorders. Numerous current and emerging
      therapies aimed at normalizing brain-gut interactions are a focus of interest,
      particularly for irritable bowel syndrome and functional dyspepsia. METHODS: A
      literature search was completed for preclinical and clinical studies related to
      central modulation of gastrointestinal functions and published in English between
      1980 and 2006. RESULTS: Existing data, while sparse, support the use of different
      classes of antidepressant drugs, including tricyclics, and selective and non
      selective serotonin reuptake inhibitors in irritable bowel syndrome. Serotonin
      receptor agonists and antagonists with peripheral and possibly central effects
      are effective in treating specific subtypes of irritable bowel syndrome. Based
      largely on theoretical and preclinical evidence, several novel compounds that
      selectively target receptors at multiple levels within the brain-gut axis such as
      neurokinin, somatostatin and corticotropin-releasing factor receptor antagonists
      are promising. CONCLUSIONS: This review discusses the rationale for modulation of
      the brain-gut axis in the treatment of functional gastrointestinal disorders and
      highlights the most promising current and future therapeutic strategies.

PMID- 16948805
TI  - Meta-analysis: terlipressin therapy for the hepatorenal syndrome.
AB  - BACKGROUND: The hepatorenal syndrome is a severe and well-known complication of
      end-stage liver disease, but its management is controversial. Recent reports have
      shown the efficacy of terlipressin therapy, a vasopressin analogue, in
      hepatorenal syndrome patients. AIM: To evaluate the efficacy and safety of
      terlipressin in the treatment of hepatorenal syndrome. METHODS: We performed a
      systematic review of the literature with a meta-analysis of clinical trials. The
      primary outcome (as a measure of efficacy) was the rate of responder patients
      (i.e. patients who had hepatorenal syndrome reversal after terlipressin therapy).
      The secondary outcomes were the rate of responders who had hepatorenal syndrome
      recurrence after terlipressin withdrawal, and the drop-out rate (as a measure of
      tolerability). We used the random effects model of DerSimonian and Laird with
      heterogeneity and sensitivity analysis. RESULTS: We identified 10 clinical trials
      (154 unique patients); two (20.0%) were randomized, controlled trials. The pooled
      rate of patients who reversed hepatorenal syndrome after terlipressin therapy was
      0.52 (95% CI, 0.42; 0.61), P = 0.0001; I2 = 24.6%. The pooled frequency of
      responder patients who showed hepatorenal syndrome recurrence after terlipressin
      withdrawal was 0.55 (95% CI, 0.40; 0.69), P = 0.00001; I2 = 44.3%. The pooled
      rate of patients who showed side-effects to terlipressin therapy was 0.29 (95%
      CI, 0.17; 0.42), P < 0.0001, I2 = 66.6%. The drop-out rate was 0%. The pooled OR
      for mortality rate in hepatorenal syndrome patients who were not responders to
      terlipressin vs. responder patients was 5.746 (95% CI, 1.5; 21.9). We did not
      find any predictive factor of response to terlipressin therapy. CONCLUSIONS: This
      meta-analysis shows efficacy and safety of terlipressin in the treatment of
      hepatorenal syndrome. However, a significant number of responder patients
      relapsed after terlipressin withdrawal. Further studies are in progress to
      address the link between terlipressin and survival in hepatorenal syndrome
      patients.

PMID- 16948806
TI  - Discontinuation of proton pump inhibitors in patients on long-term therapy: a
      double-blind, placebo-controlled trial.
AB  - BACKGROUND: The proportion of proton pump inhibitor users on long-term therapy
      who can discontinue proton pump inhibitor (PPI) medication without developing
      symptoms is unknown. AIM: To determine the proportion of patients on long-term
      PPI therapy who are able to discontinue PPIs without developing symptoms.
      METHODS: Patients on long-term PPIs, without a history of peptic ulcer or
      esophagitis underwent upper endoscopy. Patients were randomized double-blindly to
      taper down or continue a constant dosage of omeprazole for three weeks.
      Thereafter, all patients discontinued PPIs. RESULTS: Of the 97 patients enrolled,
      had used PPIs for 48 months, 78% had GERD. A total of 27% did not use PPIs during
      the year after discontinuation, 31% of the patients randomized to tapering
      discontinued PPIs and 22% of those who did not could discontinue therapy (NS).
      Gastro-oesophageal reflux disease (GERD) patients were more prone to continue
      PPIs than non-GERD patients. Only 16 (21%) of GERD patients were off PPIs vs. 48%
      of patients without GERD (p < 0.05). Serum gastrin was higher at baseline in GERD
      patients who resumed PPIs versus non-resumers (p < 0.05). GERD and serum gastrin
      were independent predictors of PPI requirement. CONCLUSIONS: Discontinuation of
      PPI was successful in 27% of long-term PPI users. GERD patients had more
      difficulty discontinuing PPIs than non-GERD patients.

PMID- 16948807
TI  - Risk factors for cardiopulmonary events during propofol-mediated upper endoscopy
      and colonoscopy.
AB  - BACKGROUND: Propofol-mediated sedation for endoscopy is popular because of its
      rapid onset and recovery profile. AIM: To examine procedure-specific occurrence
      and risk factors for cardiopulmonary events during propofol-mediated upper
      endoscopy (EGD) and colonoscopy. DESIGN: A cohort study using the Clinical
      Outcomes Research Initiative database was used to determine the frequency of
      cardiopulmonary events. Clinical Outcomes Research Initiative consisted of 69
      practice sites comprising 593 US endoscopists. Multivariate logistic regression
      analysis used variables, such as age, ASA classification and propofol
      administration by monitored anaesthesia care or gastroenterologist-administered
      propofol to determine the risk of cardiopulmonary events. RESULTS: The overall
      cardiopulmonary event rate for 5928 EGDs and 11 683 colonoscopies was 11.7/1000
      cases. For colonoscopy, ascending ASA classification was associated with an
      increased risk. Monitored anaesthesia care was associated with a decreased
      adjusted relative risk (0.5, 95% CI: 0.36-0.72). ASA I and II patients receiving
      monitored anaesthesia care for EGD exhibited a significantly lower relative risk
      (ARR 0.29, 95% CI: 0.14-0.64). For subjects with ASA class III or greater, there
      was no difference in the risk between monitored anaesthesia care and
      gastroenterologist-administered propofol. CONCLUSIONS: There are procedure
      specific risk factors for cardiopulmonary events during propofol-mediated EGD and
      colonoscopy. These should be taken into account during future prospective
      comparative trials.

PMID- 16948808
TI  - Impact of endoscopist withdrawal speed on polyp yield: implications for optimal
      colonoscopy withdrawal time.
AB  - BACKGROUND: In 2002, a U.S. Multi-Society Task Force on Colorectal Cancer
      recommended that the withdrawal phase for colonoscopy should average at least 6
      10 min. This was based on 10 consecutive colonoscopies by two endoscopists with
      different adenoma miss rates. AIMS: To characterize the relationship between
      endoscopist withdrawal time and polyp detection at colonoscopy, and to determine
      the withdrawal time that corresponds to the median polyp detection rate. DESIGN:
      Procedural data from out-patient colonoscopies performed at the Mayo Clinic,
      Rochester during 2003 were reviewed. Endoscopists were characterized by their
      mean withdrawal time for a negative procedure and individual polyp detection
      rate. RESULTS: A total of 10 955 colonoscopies performed by 43 endoscopists were
      analysed. Median withdrawal time was 6.3 min (range: 4.2-11.9); polyp detection
      rate was 44.0% (all polyps), 29.8% (< or = 5 mm), 5.9% (6-9 mm), 6.7% (10-19 mm),
      2.1% (> or = 20 mm). Longer withdrawal time was associated with higher polyp
      detection rate (r = 0.76; P < 0.0001); this relationship weakened for larger
      polyps (r = 0.19 for polyps 6-9 mm, r = 0.28 for polyps 10-19 mm, r = 0.02 for
      polyps > or = 20 mm). Overall median polyp detection rate corresponded to a
      withdrawal time of 6.7 min. CONCLUSION: Our findings support a colonoscopy
      withdrawal time of at least 7 min, which correlates with higher colon polyp
      detection rates.

PMID- 16948809
TI  - Oral V2 receptor antagonist (RWJ-351647) in patients with cirrhosis and ascites:
      a randomized, double-blind, placebo-controlled, single ascending dose study.
AB  - BACKGROUND: RWJ-351647 is a selective V2 receptor antagonist that inhibits
      vasopressin-induced water reabsorption in the kidney. AIM: To investigate the
      safety and tolerability of RWJ-351647 compared with placebo after single oral
      dose administration to patients with cirrhosis and ascites, on a stable treatment
      with furosemide and spironolactone. METHODS: Single oral doses of 1, 2 and 5 mg
      of RWJ-351647 were administered to 24 patients with ascites on stable concomitant
      diuretic treatment. RESULTS: RWJ-351647 had a tmax of 1 to 1.1 h and mean half
      life of 10.4-17.4 h. There was no affect on the pharmacokinetics of concomitant
      diuretics. Increases in cumulative urine volume and free water excretion, and a
      decrease in urine osmolality were noted in a dose-dependent manner reaching the
      statistical significance at the 5-mg dose. Four patients exhibited a decrease of
      > 2 kg in weight in the 24 h after dosing. RWJ-351647 was well tolerated, with no
      evidence of a dose-related increase in adverse events when compared with placebo.
      No changes in either serum chemistry or plasma AVP (arginine vasopressin) and
      renin levels were observed despite the observed aquaresis. CONCLUSION: RWJ-351647
      is an effective aquaretic causing dose-dependent increases in urine output and
      free water clearance, when co-administered with conventional diuretics in
      patients with cirrhosis and ascites.

PMID- 16948810
TI  - Injection of botulinum toxin before pneumatic dilatation in achalasia treatment:
      a randomized-controlled trial.
AB  - BACKGROUND: Pneumatic dilatation is the first line therapy in achalasia, but half
      of patients relapse within 5 years of therapy and require further dilatations.
      AIM: To assess whether botulinum toxin injection before pneumatic dilatation is
      superior to pneumatic dilatation alone in achalasia patients. METHODS: Newly
      diagnosed achalasia patients were randomly assigned to receive botulinum toxin 1
      month before pneumatic dilatation (botulinum toxin-pneumatic dilatation group: 27
      patients with median age of 38) or to undergo pneumatic dilatation alone
      (pneumatic dilatation group: 27 patients with median age of 30). Response to
      therapy was assessed by clinical and objective methods at various intervals.
      RESULTS: One-year remission rate of patients in botulinum toxin-pneumatic
      dilatation group was 77% compared with 62% in pneumatic dilatation group (P =
      0.1). In pneumatic dilatation group, the oesophageal barium volume significantly
      (P < 0.001) decreased at 1 month, but this reduction did not persist over 1-year
      follow-up. Botulinum toxin-pneumatic dilatation group showed a significant (P <
      0.001) reduction in barium volume at the various times intervals post-treatment.
      In the botulinum toxin-pneumatic dilatation group, 10/11 (91%) patients over 40
      were in remission at 1 year, comparing with only five of nine (55%) cases in
      pneumatic dilatation group (P = 0.07). CONCLUSION: Injection of botulinum toxin
      before pneumatic dilatation does not significantly enhance the efficacy of
      pneumatic dilatation.

PMID- 16948812
TI  - Epidemiology of candidemia in a Turkish tertiary care hospital.
AB  - In order to determine the local epidemiology of candidemia, Candida strains
      isolated between 1994 and 2000 were identified to species level; antifungal
      resistance patterns and DNA fingerprints were analyzed. Identification of Candida
      strains (n: 140) was performed with germ tube test and carbohydrate assimilation
      reactions. Minimal inhibitory concentrations were determined using a commercial
      test for 5-flucytosine and the broth macrodilution method according to NCCLS for
      fluconazole and amphotericin B. Molecular relatedness was determined by
      restriction endonuclease analysis of genomic DNA followed by probe hybridization.
      C. albicans (37.2%), C. parapsilosis (32.2%), and C. tropicalis (12.2%) comprised
      114 (81.4%) of 140 isolates. Susceptibility tests did not reveal resistance to
      amphotericin B in any of the Candida isolates. Fluconazole resistance was
      detected in one isolate of C. krusei, and 5-flucytosine resistance in two C.
      tropicalis isolates and one C. albicans isolate. Significantly higher frequency
      of clusters with identical strains in C. parapsilosis and C. tropicalis was
      detected compared to C. albicans. Pediatric wards are particularly important in
      the nosocomial transmission of non-albicans candida species.

PMID- 16948813
TI  - Adhesive capability of Lactobacillus plantarum 299v is important for preventing
      bacterial translocation in endotoxemic rats.
AB  - The preventive effect of the probiotic Lactobacillus plantarum 299v on bacterial
      translocation (BT) and the role of adhesion were studied in septic rats. Five
      groups of rats were pretreated as follows: negative and positive control groups
      received regular drinking water; the oatmeal group received drinking water mixed
      with oatmeal; the Lp 299v group received drinking water mixed with oatmeal
      containing 10(9) colony-forming units (CFU) L. plantarum 299v/ml; the Lp 299v
      adh(-) group received drinking water with oatmeal containing 10(9) CFU/ml of
      modified L. plantarum 299v (L. plantarum 299v-adh(-)) lacking adhesive properties
      to enterocytes. On day 8, all rats except the negative control group were given
      lipopolysaccharide (LPS) intraperitoneally. After 24 h, mesenteric lymph node
      (MLN), liver and ileum were harvested for culture. Incidence of BT after LPS
      challenge was 25% and 88% in MLN and liver, respectively. BT increased to 75% in
      MLN and 100% in liver of endotoxemic rats pretreated with oatmeal. Pretreatment
      with L. plantarum 299v reduced BT to 0% and 12% in MLN and liver, respectively.
      L. plantarum 299v-adh(-) did not prevent BT to MLN. Flow cytometry revealed
      reduced adherence of these bacteria to intestinal epithelial cells compared to L.
      plantarum 299v. Thus, L. plantarum 299v prevents BT in septic rats, an effect
      probably dependent on bacterial adherence to the intestinal mucosa. Further, our
      findings indicate that oatmeal (prebiotics) without probiotics does not prevent
      BT during sepsis.

PMID- 16948811
TI  - How to outwit the enemy: dendritic cells face Salmonella.
AB  - Salmonella enterica serovar Typhi causes typhoid fever, a serious life
      threatening systemic infection. In mice, a similar disease is caused by
      Salmonella enterica serovar Typhimurium. During typhoid fever, soon after
      attachment to the mucosal surface of the gut, bacteria come into contact with the
      dendritic cells (DCs). The ability to sample antigens, process and present them
      to naive and mature T cells, in the context of major histocompatibility complex
      molecules, makes DCs indispensable for mounting a specific and efficient immune
      response to invading pathogens. These bacteria, however, have evolved a number of
      mechanisms to interfere with or subvert DC functions. This review aims to
      describe how Salmonella clashes with dendritic cells at different stages of
      infection as well as the war strategies of these two opposing sides.

PMID- 16948814
TI  - Phospho-Stat3 expression and correlation with VEGF, p53, and Bcl-2 in gastric
      carcinoma using tissue microarray.
AB  - The signal transducer and activator of the transcription (Stat)-family of
      proteins are latent cytoplasmic transcription factors that transmit signals from
      cytokines and growth-factor receptors to the nucleus. Stat proteins, especially
      Stat3 and Stat5, are constitutively activated in various solid tumors and
      hematological malignancies. However, the role of Stat3 signaling in gastric
      carcinoma has not yet been fully determined. This study was conducted to
      investigate the clinical value of phospho-Stat3 expression in gastric carcinoma.
      Expression of phospho-Stat3 (Tyr705), vascular endothelial growth factor (VEGF),
      p53, and Bcl-2 was determined by immunohistochemical staining of tissue
      microarrays from 137 cases of resected gastric cancer specimens. We evaluated the
      relationships among phospho-Stat3, VEGF, p53, and Bcl-2 expression and the
      correlation between expression of these proteins and various clinicopathological
      factors, including overall survival. Phospho-Stat3 nuclear expression was
      observed in 18.2% of the cases. Of the total number of cases, 68.6% were positive
      for VEGF, 40.1% for p53, and 11.7% for Bcl-2. Phospho-Stat3 expression correlated
      with VEGF (p=0.021) and Bcl-2 (p=0.005) expression. Positive phospho-Stat3
      staining was significantly associated with poor pathological grade. However,
      there was no significant difference in other clinicopathological parameters, such
      as tumor stage (T, N, M), pathological type, relapse-free survival, and overall
      survival between the phospho-Stat3-positive and -negative groups. Co-expression
      of phospho-Stat3 and VEGF was found in many patients with N3 and Stage IV
      disease. These results suggest that phospho-Stat3 expression might be associated
      with angiogenesis, anti-apoptosis, and tumor progression. Further studies are
      needed to determine the role of phospho-Stat3 in gastric cancer.

PMID- 16948815
TI  - Histological variety of floral variant of follicular lymphoma.
AB  - To further clarify the histopathological findings of the floral variant of
      follicular lymphoma (FVFL), we studied 13 Japanese cases. Two histological
      subtypes of neoplastic follicles of FVFL have been described: (i) A macrogerminal
      center pattern where the mantle zone lymphocytes were invaginated into the
      neoplastic germinal center, often reminiscent of a floral design. (ii) A
      microgerminal center pattern where the massive invasion of mantle zone
      lymphocytes resulted in almost complete breakage of the neoplastic follicles. In
      the former pattern, the neoplastic germinal center usually contained large
      clusters of tumor cells, whereas in the latter, small clusters of up to 20 tumor
      cells or isolated tumor cells were observed in the neoplastic germinal centers.
      Moreover, occasional tumor cells showed a lymphocytic and/or histiocytic Reed
      Sternberg cell (L&H cells)-like morphology. Both types of neoplastic follicles
      were observed to a varying degree in most cases. The macrogerminal center pattern
      was predominant in nine cases (70%), whilst the microgerminal center pattern was
      predominant in only four cases (30%). Three lesions (23%) had a marginal zone
      component. Immunohistochemistry showed that atypical follicular center cells,
      including L&H cells, were CD3-, CD5-, CD10+, CD20+, CD43-, bcl-2+, cyclinD1-. The
      overall histological findings of the macrogerminal center are similar to those of
      florid progressive transformation of germinal center (PTGC), whilst the
      microgerminal center pattern is similar to that of nodular lymphocyte-predominant
      Hodgkin lymphoma. Initially, the differential diagnosis between FVFL and florid
      PTGC was emphasized. However, the present study indicates that nodal marginal
      zone B-cell lymphoma possessing floral follicles and nodular lymphocyte
      predominant Hodgkin lymphoma should be added to the differential diagnosis of
      FVFL. The germinal center B-cell nature of FVFL is most clearly recognizable by
      immunohistochemistry, though histological appearance alone may cause some
      diagnostic problems.

PMID- 16948816
TI  - Nontypeable Haemophilus influenzae strains with the capsule-associated insertion
      element IS1016 may mimic encapsulated strains.
AB  - With the elimination of Haemophilus influenzae type b through vaccination, it has
      been suggested that other types of H. influenzae strains might acquire virulence
      traits and emerge as important pathogens. The gene sequence IS1016 has been
      associated with an increased capacity to cause severe infections. It is usually
      present in encapsulated strains but is sometimes harbored by nontypeable H.
      influenzae strains. To explore this further, 118 H. influenzae isolates,
      collected from both patients and healthy carriers, were investigated with PCR
      with reference to this gene sequence. Isolates positive for the insertion element
      were bio- and serotyped. The presence of hmw genes for adherence, the genetic
      profile, and the ability to form biofilm in vitro were investigated. A total of
      15 isolates were IS1016-positive, whereof 12 were nontypeable. All 12 nontypeable
      isolates were obtained from healthy carriers, and 92% of the isolates were
      biotype I. They cross-reacted to some extent with type-specific antisera or
      exhibited a restricted genetic diversity like encapsulated strains. Furthermore,
      they lacked hmw-genes, and their ability to form biofilms was comparable with a
      capsule-deficient type b strain. Although this subset of strains mimicked traits
      usually exhibited by encapsulated strains, the isolation frequency did not seem
      to have been affected by vaccination.

PMID- 16948817
TI  - High incidence of intravascular focus in nontyphoid Salmonella bacteremia in the
      age group above 50 years: a population-based study.
AB  - Questions regarding the relative frequency of vascular complications in
      nontyphoid Salmonella bacteremia are pending, and the true population-based age
      related incidence is not known. We reviewed all cases of nontyphoid Salmonella
      bacteremia during a 10-year period from 1994 through 2003 in a well-defined
      population of 492,843 residents in North Jutland County, Denmark. 77 of a total
      of 111 cases occurred in patients >50 years old. In this age group, five cases of
      mycotic aneurysm and two cases of endocarditis were documented, corresponding to
      a 9% occurrence. The annual incidence rate of endovascular nontyphoid Salmonella
      infection in this age group was 4.4 per 1,000,000 person years. The mortality was
      43% in cases with endovascular infection, and surgical procedures were important
      for survival. We conclude that in patients older than 50 years, detection of
      nontyphoid Salmonella bloodstream infection should be followed by examinations
      for mycotic aneurysms and endocarditis.

PMID- 16948818
TI  - Mutational analysis of the CASP6 gene in colorectal and gastric carcinomas.
AB  - Failure of apoptosis is one of the hallmarks of cancer. As an execution-phase
      caspase, caspase-6 plays a crucial role during apoptosis. To explore the
      possibility that the genetic alterations of CASP, which encodes caspase-6, might
      be involved in the development of human cancers, we analyzed the entire coding
      region and all splice sites of the human CASP6 gene for the detection of somatic
      mutations in 100 colorectal carcinomas and 50 gastric carcinomas. Overall, we
      detected three somatic mutations of the CASP6 gene, including two missense
      mutations and one splice-site mutation. The mutations were observed in two of the
      100 colorectal carcinomas (2.0%) and one of the 50 gastric carcinomas (2.0%). Of
      note, one colorectal carcinoma with the CASP6 mutation harbored CASP3 and CASP8
      gene mutations as well. We also analyzed caspase-6 expression by
      immunohistochemistry, and found that caspase-6 was expressed in 60% of the
      gastric cancers and 90% of the colorectal cancers. This is the first report on
      CASP6 gene mutations in human cancers, and these data indicate that the CASP6
      gene is occasionally mutated in gastric and colorectal carcinomas. Also, the data
      suggest the possibility that deficiency of caspase-6 expression might contribute
      to the pathogenesis of gastric cancers.

PMID- 16948819
TI  - Low-grade endometrial stromal sarcoma with sex cord-like differentiation
      metastatic to the thoracic spines.
AB  - We report a case of monostotic low-grade stromal sarcoma (ESS) with sex cord-like
      elements metastatic to the thoracic spines, which to the best of our knowledge
      has not previously been documented. A 48-year-old female who had undergone total
      abdominal hysterectomy for low-grade endometrial stromal sarcoma 7 years
      previously presented with insidious onset of severe back pain of 2 months'
      duration. Magnetic resonance image (MRI) showed involvement of the eleventh and
      twelfth thoracic vertebral bodies. Decompression at the level of T10-12 was
      performed. Histologically, the laminae of thoracic vertebrae 11 and 12 were
      replaced by sheets of ovoid cells with plump nuclei intermixed with anastomosing
      trabeculae, cords and small nests, reminiscent of a sex-cord stromal tumor
      pattern. The tumor cells showed diffuse nuclear immunostaining for estrogen
      receptors (ER) and progesterone receptors (PR), as well as membranous
      immunostaining for CD10. The immunostaining for smooth muscle actin was focal and
      sparse. These findings confirmed the diagnosis of metastatic low-grade ESS with
      sex cord-like differentiation. Low-grade ESS with sex cord-like differentiation
      is an uncommon tumor which rarely metastasizes to the bone, and use of a panel of
      ER, PR, CD10, actin, cytokeratin and inhibin immunostains is essential to
      establish the diagnosis.

PMID- 16948820
TI  - Rapid diagnosis of Mycobacterium tuberculous peritonitis with real-time PCR in a
      peritoneal dialysis patient.
AB  - A 49-year-old female patient on continuous ambulatory peritoneal dialysis
      presented with fever, abdominal pain and loss of appetite. While peritoneal fluid
      bacterial cultures remained negative, she had no relief after 3 weeks of broad
      spectrum antibiotics for possible bacterial peritonitis. In a peritoneal fluid
      sample, Mycobacterium tuberculosis DNA was detected by nucleic acid amplification
      using real-time PCR testing. The initiation of antituberculous therapy
      (isoniazid, rifampicin, ethambutol and pyrazinamide) was followed by resolution
      of fever and abdominal pain within one week. Nucleic acid amplification tests can
      play an important role in the species-specific diagnosis of tuberculous
      peritonitis.

PMID- 16948821
TI  - Granular cell tumor arising metachronously in the bronchus and esophagus.
AB  - We present a case of granular cell tumor (GCT) occurring in the esophagus 7 years
      after operation for bronchial GCT. A 59-year-old Japanese man complained of
      epigastralgia, and endoscopic examination of the upper digestive tract disclosed
      a submucosal tumor in the lower esophagus. Histological examination of the
      endoscopic mucosal resection of the esophageal tumor showed a proliferation of
      neoplastic cells with an eosinophilic and granular cytoplasm. The cytoplasm of
      the neoplastic cells was histochemically positive for PAS stain and
      immunohistochemically positive for S-100. This tumor did not fulfill any of the
      diagnostic criteria for malignancy at either the macroscopic or microscopic
      level. I believe that this is the first case of GCT occurring metachronously in
      the respiratory and digestive tracts. Clinicians and pathologists should bear in
      mind that GCT may arise metachronously in the respiratory and digestive tracts.

PMID- 16948822
TI  - Orbital giant cell angiofibroma.
AB  - A case of giant cell angiofibroma in a 73-year-old man is reported. The tumour
      was located in the upper-inner quadrant of the right orbit and recurred 16 months
      after surgical removal. The clinicopathological features of this rare neoplasm-
      that is nowadays considered a variant of solitary fibrous tumour--are reviewed
      and briefly commented on.

PMID- 16948823
TI  - Myeloid sarcoma of the extrahepatic bile ducts presenting as obstructive
      jaundice.
AB  - We report a rare case of myeloid sarcoma (MS) of the extrahepatic bile ducts
      presenting as obstructive jaundice in a patient without leukemia at time of
      diagnosis. A 75-year-old female presented with a one-month history of abdominal
      pain and jaundice. Computerized tomography scan of the abdomen showed stenosis of
      the extrahepatic bile ducts. Endoscopic retrograde cholangiography disclosed an
      irregular narrowing of the common biliary duct, suggestive of a
      cholangiocarcinoma, and resection was performed. Histologic examination showed
      diffuse transmural infiltration of malignant cells. These cells exhibited medium
      sized round nuclei with central nucleoli and eosinophilic cytoplasm, and were
      strongly positive for myeloperoxidase, CD68, lysozyme, CD45, CD117 (c-kit
      protein) and CD43. Eight months following surgery the patient presented with
      multiple cutaneous nodules and bone marrow trephine biopsy showed acute
      myelomonocytic leukemia. A literature search identified two previously reported
      cases of MS of the extrahepatic biliary duct. MS should be taken into
      consideration in the differential diagnosis of a patient with obstructive
      jaundice. Immunohistochemistry is essential for a correct diagnosis.

PMID- 16948824
TI  - Broad-band ultraviolet B phototherapy in zoster patients may reduce the incidence
      and severity of postherpetic neuralgia.
AB  - BACKGROUND: Postherpetic neuralgia (PHN) is one of the common complications of
      herpes zoster infection, particularly in the elderly. Current therapeutic
      measures are only partially effective in the affected patients. As inflammatory
      mediators released by different cells play an important role in the pathogenesis
      of this neuropathic pain and with regard to the immunomodulatory effects of
      ultraviolet B (UVB) spectrum, we presumed that UVB phototherapy might be
      effective in the prevention of PHN. METHOD: This study was performed in two
      phases. Phase I was a prospective open controlled trial. Twenty-five patients
      with severe pain in the first 7 days of zoster rash were divided into two groups:
      the prevention group (n=12) received oral acyclovir (800 mg five times a day for
      10 days) plus broad-band UVB to the affected dermatomes, starting with 20
      mJ/cm(2) and gradually increasing the dose by 10 mJ/cm(2) each session to a
      maximum dose of 100 mJ/cm(2). Treatment sessions were repeated three times a week
      until pain relief or to a maximum of 15 sessions. The control group (n=13), who
      had disease characteristics similar to the prevention group, received only oral
      acyclovir with the same dose. All patients reported their severity of pain on a
      verbal rating scale (VRS, score 0-4) before treatment and at 1 and 3 months'
      follow-up. In phase II of the study, five patients with established PHN (more
      than 3 months after rash onset) received UVB with the above-mentioned protocol.
      RESULTS: A total of 17 patients older than 40 (10 females, seven males; mean age,
      65.5 years; range: 47-82 years) who had intractable pain due to zoster infection
      received UVB in two phases of the study. In patients who received phototherapy in
      the first 7 days of rash, 58.33% and 83.33% were completely pain free at 1-and 3
      month follow-up, respectively. The corresponding figure in the control group was
      significantly lower (38.46% at 1 month and 53.85% at 3 months). The severity of
      pain was also lower in the phototherapy group than the control group (mean VRS
      2.50 vs. 3.28 at 3 months). None of the patients who were treated more than 3
      months after rash onset (established PHN) experienced significant (more than 50%)
      pain relief. CONCLUSION: UVB phototherapy in the acute stage of zoster rash might
      reduce the incidence and severity of PHN. Treatment after 3 months does not seem
      to have a significant beneficial effect.

PMID- 16948825
TI  - Evidence for a bystander role of neutrophils in the response to systemic 5
      aminolevulinic acid-based photodynamic therapy.
AB  - BACKGROUND/PURPOSE: A significant increase in the number of circulating and
      tumour neutrophils immediately after therapy was observed while investigating the
      increase in response of tissues to aminolevulinic acid-based photodynamic therapy
      (ALA-PDT) using a twofold illumination scheme with a prolonged dark interval. The
      action of (tumour) neutrophils is an important therapeutic adjunct to the
      deposition of singlet oxygen within the treatment volume, for many
      photosensitizers. It is not known if those phagocytes contribute to the improved
      outcome of ALA-PDT. In this study we investigated the role of neutrophils in the
      response to PDT using systemic ALA with and without light fractionation. METHODS:
      Rhabdomyosarcoma, transplanted in the thigh of female WAG/Rij rats were
      illuminated transdermally using 633 nm light following i.v. administration of 200
      mg/kg ALA. The pharmacokinetics of protoporphyrin IX (PpIX) within the tumour
      tissue during therapy were determined to compare with that observed in other
      models for topical administration of ALA. PDT was performed under immunologically
      normal or neutropenic conditions using various illumination schemes. The number
      of neutrophils in tumour and in the circulation were determined as a function of
      time after treatment and compared with growth delay of each scheme. RESULTS:
      Fluorescence spectroscopy revealed similar pharmacokinetics of PpIX to those
      observed during and after topical ALA-PDT. The number of neutrophils within the
      illuminated tumour and in the circulation increased significantly following
      therapy. This increase in the number of neutrophils was associated with an
      increase in the efficacy of therapy: the more effective the therapy the greater
      the increase in tumour and blood neutrophils. Administration of anti-granulocyte
      serum treatment prevented the influx of neutrophils after ALA-PDT, but did not
      lead to a significant decrease in the efficacy of the PDT treatment on the growth
      of the tumour for any illumination scheme investigated. CONCLUSION: These results
      indicate that the magnitude of damage inflicted on the tumour by ALA-PDT does not
      depend on the presence of neutrophils in the tumour or circulation and that the
      role of neutrophils in ALA-PDT is much less important than in PDT using other
      photosensitizers. These data contribute to the understanding of the mechanism of
      response of tissue to systemic ALA-PDT.

PMID- 16948826
TI  - UVA1 phototherapy for cutaneous diseases: an experience of 92 cases in the United
      States.
AB  - BACKGROUND: The efficacy and safety of UVA1 (340-400 nm) phototherapy were
      established by studies from European countries. PURPOSE: Evaluate experience with
      UVA1 phototherapy for patients with cutaneous diseases in the United States.
      METHODS: A retrospective analysis of 92 cases of UVA1-treated cutaneous
      conditions from four medical centers in the United States was performed. RESULTS:
      Two-third of the patients showed a fair to good response (26-100% improvement)
      and one-third of the patients showed a poor response (0-25% improvement).
      Diseases with a moderate to good response (51-100% improvement) included
      scleredema adultorum, hand or foot dermatitis, atopic dermatitis, morphea (medium
      or medium- to high-dose UVA1), systemic sclerosis, and urticaria pigmentosa.
      Besides tanning, other adverse effects were found in 15% of patients, which
      include pruritus, erythema, tenderness, and burning sensation. Patients with skin
      types I-III responded better that those with a darker skin type. CONCLUSION: UVA1
      phototherapy is a useful and well-tolerated treatment option for a variety of
      skin conditions.

PMID- 16948827
TI  - Photodynamic therapy with methylaminolevulinate as a valuable treatment option
      for unilesional cutaneous T-cell lymphoma.
AB  - BACKGROUND: Mycosis fungoides (MF) is the most common primary cutaneous T-cell
      lymphoma (CTCL). Unilesional MF is characterized by a limited involvement of the
      skin and a chronical, though indolent course. If lesions are refractory to
      topical steroids, therapies such as localized chemotherapy, photochemotherapy and
      radiotherapy are available. However, they have several acute and chronic side
      effects and toxicity may accumulate if repeated and protracted treatment cycles
      are delivered to refractory or relapsing lesions. The present study aims to
      assess the efficacy of photodynamic therapy (PDT) with topical
      methylaminolevulinate (MAL) in the treatment of unilesional MF. METHODS: Five
      patients were enrolled who had unilesional MF that did not respond to treatment
      with topical steroids, localized psoralen and UVA therapy or UVA1 phototherapies.
      A 20% MAL (Metvix cream) cream was applied under occlusive dressing for 3 h. Soon
      afterwards, skin was irradiated with 37.5 J/cm(2) of red light (635+/-18 nm)
      delivered by an Aktilite CL128 lamp (PhotoCure ASA) with an irradiance of 86
      W/cm(2) at skin level. PDT was repeated once weekly until complete clearing of
      the lesions was obtained, or, in the case of partial clearing, the therapy was
      interupted when three successive treatments provided no further improvement. All
      patients underwent a skin biopsy before and after PDT. RESULTS: A complete
      remission was observed in four patients and a partial improvement in one. The
      median number of treatments was six (range 1-9). In no cases was recurrence seen
      at follow-up (ranging from 12 to 34 months). Treatments were well tolerated and
      local anesthesia was never requested. CONCLUSION: In conclusion, here, PDT was
      seen to be an effective and well-tolerated treatment option for unilesional MF.

PMID- 16948828
TI  - Parry-Romberg syndrome associated with borreliosis: could photochemotherapy halt
      the progression of the disease?
AB  - Parry-Romberg syndrome (PRS) or progressive hemifacial atrophy is a rare entity
      characterized by unilateral atrophy of the skin, subcutaneous tissue and
      sometimes bone and cartilage. Although this syndrome has overlapping features of
      scleroderma 'en coup de sabre', it shows little or no sclerosis and may affect
      the entire distribution of the trigeminal nerve including the eye and tongue. As
      the pathogenesis is unknown, no effective therapy exists. We present here the
      third case of PRS associated with borreliosis and more interestingly two cases
      whose progressive course have been stabilized with gel PUVA therapy.

PMID- 16948829
TI  - Comparison of the efficacy of calcipotriol and maxacalcitol in combination with
      narrow-band ultraviolet B therapy for the treatment of psoriasis vulgaris.
AB  - BACKGROUND: Combination treatment with topical vitamin D(3) and narrow-band
      ultraviolet B (UVB) radiation is effective against psoriasis vulgaris. We
      compared the efficacy of the topical vitamin D(3) derivatives calcipotriol and
      maxacalcitol in combination therapy. MATERIALS AND METHODS: In this retrospective
      observational study, 21 patients admitted to Nagoya City University Hospital
      between April 2001 and September 2004 were enrolled. RESULTS: Combination
      treatment with calcipotriol or maxacalcitol and narrow-band UVB was effective
      against psoriasis vulgaris. Calcipotriol induced a more rapid improvement and
      required lower levels of narrow-band UVB irradiation to be effective. Serum
      calcium levels were slightly increased after 4 weeks of treatment, but there was
      no significant difference between the two groups. No other adverse effects were
      observed in either of the two groups. CONCLUSION: The findings of this
      retrospective observational study indicated that combination treatment with
      topical vitamin D(3) derivatives and narrow-band UVB is effective against
      psoriasis without any obvious side-effects. These findings provide further
      evidence that calcipotriol has advantages over maxacalcitol regarding the narrow
      band UVB-accumulated treatment dose and improvement rate of psoriasis area and
      severity index (PASI) scores.

PMID- 16948830
TI  - Treatment of multiple warts in a renal transplant recipient with decreased laser
      doses after application of a light absorbing dye.
AB  - BACKGROUND/PURPOSE: Multiple warts are a tremendous problem in immunosuppressed
      patients. Standard treatment has low efficacy and is often painful. We examined a
      new treatment combination of gentian violet and dye-laser. METHODS: A 55-year-old
      male renal transplant recipient was treated with dye-laser at 585 nm after
      application of gentian violet 0.5%. RESULTS: One laser pulse made the stain
      explode and evaporate and resulted in a considerable reduction in warts size with
      minimal pain and tissue damage. CONCLUSION: Application of gentian violet before
      dye-laser treatment may be effective in the battle against warts in
      immunocompromised patients.

PMID- 16948831
TI  - Effect of topical melatonin on ultraviolet radiation-induced suppression of
      Mantoux reactions in humans.
AB  - BACKGROUND: Melatonin, the central neurohormone in circadian rhythm pathways, is
      recognized to have a variety of immune-enhancing effects. It has previously been
      shown to reduce ultraviolet (UV) radiation-induced erythema in mice and in
      humans, but there are as yet no published studies on the effects of melatonin on
      UV-induced immunosuppression in humans. METHODS: We investigated the effects of
      topical melatonin on solar-simulated (ss) UV-induced suppression of Mantoux
      reactions in 16 healthy, Mantoux-positive volunteers. Melatonin (5%) and its
      vehicle were applied in a double-blinded manner to separate areas on the lower
      back, immediately after each of three consecutive daily ssUV exposures. Various
      sites on the back received either no irradiation or one of three-graded ssUV
      doses. Mantoux testing was performed at each site 24 h after the final
      irradiation, and assessed 72 h later using a reflectance erythema meter. In a
      separate group of 19 volunteers, the effect of melatonin on minimal erythema dose
      was assessed both visually and with an erythema meter. RESULTS: We found dose
      responsive UV-induced suppression of the Mantoux response in the presence of both
      vehicle and melatonin; melatonin did not prevent UV-induced immunosuppression in
      this model. Melatonin was also found to have no effect on the minimal erythema
      dose. CONCLUSIONS: Melatonin conferred no protection against immune suppression
      or sunburn when applied topically to human skin immediately after irradiation.

PMID- 16948832
TI  - The utility of a data-logging device for measuring adherence to home
      phototherapy.
AB  - BACKGROUND: Treatment adherence to home phototherapy is not well characterized.
      PURPOSE: To develop an accurate measure of home phototherapy unit usage. METHODS:
      We tested a commercially available data logger containing a photo-sensor on two
      home phototherapy units. RESULTS: The data logger accurately recorded actual
      usage and did not record stray light sources over the study period. CONCLUSION: A
      data logger can accurately capture usage patterns for a home phototherapy unit.
      These devices could potentially be used in clinical trials to measure adherence
      to home phototherapy treatment regimens.

PMID- 16948833
TI  - Open comedones overlying granuloma annulare in a photoexposed area.
AB  - A 57-year-old, fair-skinned female patient with lesions of granuloma annulare
      located on her forearms - with signs of actinic damage - is described. No
      response was observed after successive treatments with topical corticosteroids
      and oral pentoxifylline. Four years later, the patient developed open comedones
      on the rim of granuloma annulare lesions. The loss of elastic fibers seen in both
      granuloma annulare and solar elastosis is presumed to have induced the appearance
      of open comedones, because of a loss of supporting properties of the dermis
      inducing a distension of the infundibular canal of the sebaceous follicle, as
      seen in the Favre-Racouchot disease and actinic comedonal plaque. Concomitantly,
      the patient developed insulin-dependent diabetes mellitus. Treatment with insulin
      resulted in the disappearance of open comedones and notably regression of lesions
      of granuloma annulare. Response to insulin therapy in our case supports the
      hypothesis that insulinopenia could participate in the development of granuloma
      annulare in some cases.

PMID- 16948834
TI  - Genital tuberculosis in a tamoxifen-treated postmenopausal woman with breast
      cancer and bloody vaginal discharge.
AB  - BACKGROUND: Female genital tuberculosis is an uncommon disease that is rarely
      diagnosed in developed countries. CASE PRESENTATION: A 61-year-old postmenopausal
      woman who had undergone surgery and treated with adjuvant chemotherapy for
      infiltrating ductal carcinoma of the breast five years ago, presented with bloody
      vaginal discharge, fatigue, weight loss, and low grade fevers at night for two
      months. Histological examination of the endometrium, done based on the suspicion
      of a second primary cancer due to the tamoxifen therapy, revealed a granulomatous
      reaction. Liquid and solid mycobacterial cultures of the tissues were performed.
      Although the acid fast staining was negative, the liquid culture was positive for
      Mycobacterium tuberculosis. Involvement of other systems was not detected. The
      patient was treated with a three-drug antituberculosis regimen for 9 months and
      recovered fully. CONCLUSION: Female genital tuberculosis is a rare but curable
      disease that should be included in the differential diagnosis of women with
      menstrual problems. Early diagnosis is important and may prevent unnecessary
      invasive procedures for the patient.

PMID- 16948835
TI  - The relationship between quality of research and citation frequency.
AB  - BACKGROUND: Citation counts are often regarded as a measure of the utilization
      and contribution of published articles. The objective of this study is to assess
      whether statistical reporting and statistical errors in the analysis of the
      primary outcome are associated with the number of citations received. METHODS: We
      evaluated all original research articles published in 1996 in four psychiatric
      journals. The statistical and reporting quality of each paper was assessed and
      the number of citations received up to 2005 was obtained from the Web of Science
      database. We then examined whether the number of citations was associated with
      the quality of the statistical analysis and reporting. RESULTS: A total of 448
      research papers were included in the citation analysis. Unclear or inadequate
      reporting of the research question and primary outcome were not statistically
      significantly associated with the citation counts. After adjusting for journal,
      extended description of statistical procedures had a positive effect on the
      number of citations received. Inappropriate statistical analysis did not affect
      the number of citations received. Adequate reporting of the primary research
      question, statistical methods and primary findings were all associated with the
      journal visibility and prestige. CONCLUSION: In this cohort of published
      research, measures of reporting quality and appropriate statistical analysis were
      not associated with the number of citations. The journal in which a study is
      published appears to be as important as the statistical reporting quality in
      ensuring dissemination of published medical science.

PMID- 16948836
TI  - The human urinary proteome contains more than 1500 proteins, including a large
      proportion of membrane proteins.
AB  - BACKGROUND: Urine is a desirable material for the diagnosis and classification of
      diseases because of the convenience of its collection in large amounts; however,
      all of the urinary proteome catalogs currently being generated have limitations
      in their depth and confidence of identification. Our laboratory has developed
      methods for the in-depth characterization of body fluids; these involve a linear
      ion trap-Fourier transform (LTQ-FT) and a linear ion trap-orbitrap (LTQ-Orbitrap)
      mass spectrometer. Here we applied these methods to the analysis of the human
      urinary proteome. RESULTS: We employed one-dimensional sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and reverse phase high-performance liquid
      chromatography for protein separation and fractionation. Fractionated proteins
      were digested in-gel or in-solution, and digests were analyzed with the LTQ-FT
      and LTQ-Orbitrap at parts per million accuracy and with two consecutive stages of
      mass spectrometric fragmentation. We identified 1543 proteins in urine obtained
      from ten healthy donors, while essentially eliminating false-positive
      identifications. Surprisingly, nearly half of the annotated proteins were
      membrane proteins according to Gene Ontology (GO) analysis. Furthermore,
      extracellular, lysosomal, and plasma membrane proteins were enriched in the urine
      compared with all GO entries. Plasma membrane proteins are probably present in
      urine by secretion in exosomes. CONCLUSION: Our analysis provides a high
      confidence set of proteins present in human urinary proteome and provides a
      useful reference for comparing datasets obtained using different methodologies.
      The urinary proteome is unexpectedly complex and may prove useful in biomarker
      discovery in the future.

PMID- 16948837
TI  - Patient acceptability of larval therapy for leg ulcer treatment: a randomised
      survey to inform the sample size calculation of a randomised trial.
AB  - BACKGROUND: A trial was commissioned to evaluate the effectiveness of larval
      therapy to debride and heal sloughy and necrotic venous leg ulcers. Larval
      therapy in the trial was to be delivered in either loose or bagged form.
      Researchers were concerned that resistance to larval therapy may threaten the
      feasibility of the trial. Additionally there was concern that the use of larval
      therapy may require a larger effect size in time to healing than originally
      proposed by the investigators. METHODS: To formally evaluate patient preferences
      a survey using two randomly allocated, nurse administered questionnaires was
      undertaken. Patients were randomised to receive one of the two following
      questionnaires (i) preferences between loose larvae and standard treatment
      (hydrogel) or (ii) patient preferences between bagged larvae and standard therapy
      (hydrogel). The study was undertaken in a Vascular Clinic, in an Outpatients
      Department of a large teaching hospital in the North of England. The sample
      consisted of 35 people aged 18 years and above with at least one leg ulcer of
      venous or mixed (venous and arterial) aetiology. RESULTS: Approximately 25% of
      participants would not consider the use of larval therapy as an acceptable
      treatment option for leg ulcers, regardless of the method of containment. For the
      patients that would consider the use of larval therapy, different preferences in
      healing times required to use the therapy were observed depending upon the method
      of containment. The median response of those participants questioned about bagged
      larvae found that they would be willing to use this therapy even if they were
      equally able to achieve healing with the use of hydrogel by 20 weeks. For those
      participants questioned about the use of loose larvae complete healing would have
      to have taken place over 17 weeks for them to choose larvae as their preferred
      option rather than hydrogel. This difference was not significant (p = 0.075).
      CONCLUSION: We found no evidence of widespread resistance to the utilisation of
      larval therapy from patients regardless of the method of larval therapy
      containment. These methods have the potential to inform sample size calculations
      where there are concerns of patient acceptability.

PMID- 16948838
TI  - Implementing chlamydia screening: what do women think? A systematic review of the
      literature.
AB  - BACKGROUND: Chlamydia trachomatis is a common sexually transmitted infection that
      can have serious consequences. It is universally agreed that screening for
      chlamydia infection should be offered to sexually active young women. We
      undertook a literature review to document the views, attitudes and opinions of
      women about being screened, tested and diagnosed with Chlamydia trachomatis.
      METHODS: Online databases (MEDLINE, Meditext, PsycINFO, Web of Science) and
      reference lists searched up to August 2005. Search terms: chlamydia, attitude,
      attitude to health, interview, qualitative, women. ELIGIBILITY CRITERIA: about
      chlamydia, included women, involved interviews/surveys/focus groups, looked at
      women's views/opinions/attitudes, published in English. Thematic analysis
      identified the main and recurrent themes emerging from the literature. We
      compared our thematic analysis with the Theory of Planned Behaviour to provide a
      model that could assist in planning chlamydia screening programs. RESULTS: From
      561 identified articles, 25 fulfilled inclusion criteria and were reviewed. 22:
      USA, UK; 3: Holland, Sweden, Australia. Major themes identified: need for
      knowledge and information, choice and support; concerns about confidentiality,
      cost, fear, anxiety and stigma. Women are more likely to find chlamydia
      screening/testing acceptable if they think chlamydia is a serious, common
      condition which can cause infertility and if they understand that chlamydia
      infection can be asymptomatic. Women want a range of options for chlamydia
      testing including urine tests, self-administered swabs, pelvic exams and
      clinician-collected swabs, home-testing and community-based testing. Tests should
      be free, easy and quick. Women want support for dealing with the implications of
      a chlamydia diagnosis, they feel chlamydia diagnoses need to be normalised and
      destigmatised and they want assistance with partner notification. Women need to
      know that their confidentiality will be maintained. CONCLUSION: Our review found
      that women from various countries and ethnic backgrounds share similar views
      regarding chlamydia screening, testing and diagnosis. The acknowledged importance
      of women's views in planning an effective chlamydia screening program is expanded
      in this review which details the nature and complexity of such views and
      considers their likely impact.

PMID- 16948839
TI  - Factors influencing consumer dietary health preventative behaviours.
AB  - BACKGROUND: The deterioration of the health status of the Romanian population
      during the economic transition from a centrally planned to a free market economy
      has been linked to lifestyles factors (e.g. diet) regarded as a main determinants
      of the disparity in life expectancy between Eastern and Western Europe. Reforms
      in the health care system in this transition economy aim to focus on preventive
      action. The purpose of this study was to identify the factors that impact on the
      individual decision to engage in Dietary Health Preventive Behaviour (DHPB) and
      investigate their influence in the context of an adapted health cognition model.
      METHODS: A population-based study recruited 485 adult respondents using random
      route sampling and face-to-face administered questionnaires. RESULTS AND
      DISCUSSION: Respondents' health motivation, beliefs that diet can prevent
      disease, knowledge about nutrition, level of education attainment and age have a
      positive influence on DHPB. Perceived barriers to healthy eating have a negative
      impact on alcohol moderation. The information acquisition behaviour (frequency of
      reading food labels) is negatively predicted by age and positively predicted by
      health motivation, education, self-reported knowledge about nutrition and
      household financial status. A significant segment of respondents believe they are
      not susceptible to the elicited diseases. Health promotion strategies should aim
      to change the judgments of health risk. CONCLUSION: The adaptation of the Health
      Belief Model and the Theory of Health Preventive Behaviour represents a valid
      framework of predicting DHPB. The negative sign of perceived threat of disease on
      DHPB may suggest that, under an income constraint, consumers tend to trade off
      long-term health benefits for short-term benefits. This cautions against the use
      of negative messages in public health campaigns. Raising the awareness of diet
      disease relationships, knowledge about nutrition (particularly sources and risks
      associated with dietary fat and cholesterol) may induce people to adopt
      preventive dietary habits.

PMID- 16948840
TI  - Microarray identifies ADAM family members as key responders to TGF-beta1 in
      alveolar epithelial cells.
AB  - The molecular mechanisms of Idiopathic Pulmonary Fibrosis (IPF) remain elusive.
      Transforming Growth Factor beta 1(TGF-beta1) is a key effector cytokine in the
      development of lung fibrosis. We used microarray and computational biology
      strategies to identify genes whose expression is significantly altered in
      alveolar epithelial cells (A549) in response to TGF-beta1, IL-4 and IL-13 and
      Epstein Barr virus. A549 cells were exposed to 10 ng/ml TGF-beta1, IL-4 and IL-13
      at serial time points. Total RNA was used for hybridisation to Affymetrix Human
      Genome U133A microarrays. Each in vitro time-point was studied in duplicate and
      an average RMA value computed. Expression data for each time point was compared
      to control and a signal log ratio of 0.6 or greater taken to identify significant
      differential regulation. Using normalised RMA values and unsupervised Average
      Linkage Hierarchical Cluster Analysis, a list of 312 extracellular matrix (ECM)
      proteins or modulators of matrix turnover was curated via Onto-Compare and Gene
      Ontology (GO) databases for baited cluster analysis of ECM associated genes.
      Interrogation of the dataset using ontological classification focused cluster
      analysis revealed coordinate differential expression of a large cohort of
      extracellular matrix associated genes. Of this grouping members of the ADAM (A
      disintegrin and Metalloproteinase domain containing) family of genes were
      differentially expressed. ADAM gene expression was also identified in EBV
      infected A549 cells as well as IL-13 and IL-4 stimulated cells. We probed
      pathologenomic activities (activation and functional activity) of ADAM19 and
      ADAMTS9 using siRNA and collagen assays. Knockdown of these genes resulted in
      diminished production of collagen in A549 cells exposed to TGF-beta1, suggesting
      a potential role for these molecules in ECM accumulation in IPF.

PMID- 16948841
TI  - Enhanced radiation sensitivity and radiation recall dermatitis (RRD) after
      hypericin therapy -- case report and review of literature.
AB  - BACKGROUND: Modern radiotherapy (RT) reduces the side effects at organ at risk.
      However, skin toxicity is still a major problem in many entities, especially head
      and neck cancer. Some substances like chemotherapy provide a risk of increased
      side effects or can induce a "recall phenomenon" imitating acute RT-reactions
      months after RT. Moreover, some phototoxic drugs seem to enhance side effects of
      radiotherapy while others do not. We report a case of "radiation recall
      dermatitis" (RRD) one year after RT as a result of taking hypericin (St. John's
      wort). CASE REPORT: A 65 year old man with completely resected squamous cell
      carcinoma of the epiglottis received an adjuvant locoregional RT up to a dose of
      64.8 Gy. The patient took hypericin during and months after RT without informing
      the physician. During radiotherapy the patient developed unusual intensive skin
      reactions. Five months after RT the skin was completely bland at the first follow
      up. However, half a year later the patient presented erythema, but only within
      the area of previously irradiated skin. After local application of a steroid
      cream the symptoms diminished but returned after the end of steroid therapy. The
      anamnesis disclosed that the patient took hypericin because of depressive mood.
      We recommended to discontinue hypericin and the symptoms disappeared afterward.
      CONCLUSION: Several drugs are able to enhance skin toxicity of RT. Furthermore,
      the effect of RRD is well known especially for chemotherapy agents such as
      taxans. However, the underlying mechanisms are not known in detail so far.
      Moreover, it is unknown whether photosensitising drugs can also be considered to
      increase radiation sensitivity and whether a recall phenomenon is possible. The
      first report of a hypericin induced RRD and review of the literature are
      presented. In clinical practise many interactions between drugs and radiotherapy
      were not noticed and if registered not published. We recommend to ask especially
      for complementary or alternative drugs because patients tend to conceal such
      medication as harmless.

PMID- 16948842
TI  - The complete sequences and gene organisation of the mitochondrial genomes of the
      heterodont bivalves Acanthocardia tuberculata and Hiatella arctica--and the first
      record for a putative Atpase subunit 8 gene in marine bivalves.
AB  - BACKGROUND: Mitochondrial (mt) gene arrangement is highly variable among molluscs
      and especially among bivalves. Of the 30 complete molluscan mt-genomes published
      to date, only one is of a heterodont bivalve, although this is the most diverse
      taxon in terms of species numbers. We determined the complete sequence of the
      mitochondrial genomes of Acanthocardia tuberculata and Hiatella arctica,
      (Mollusca, Bivalvia, Heterodonta) and describe their gene contents and genome
      organisations to assess the variability of these features among the Bivalvia and
      their value for phylogenetic inference. RESULTS: The size of the mt-genome in
      Acanthocardia tuberculata is 16.104 basepairs (bp), and in Hiatella arctica
      18.244 bp. The Acanthocardia mt-genome contains 12 of the typical protein coding
      genes, lacking the Atpase subunit 8 (atp8) gene, as all published marine
      bivalves. In contrast, a complete atp8 gene is present in Hiatella arctica. In
      addition, we found a putative truncated atp8 gene when re-annotating the mt
      genome of Venerupis philippinarum. Both mt-genomes reported here encode all genes
      on the same strand and have an additional trnM. In Acanthocardia several large
      non-coding regions are present. One of these contains 3.5 nearly identical copies
      of a 167 bp motive. In Hiatella, the 3' end of the NADH dehydrogenase subunit
      (nad)6 gene is duplicated together with the adjacent non-coding region. The gene
      arrangement of Hiatella is markedly different from all other known molluscan mt
      genomes, that of Acanthocardia shows few identities with the Venerupis
      philippinarum. Phylogenetic analyses on amino acid and nucleotide levels robustly
      support the Heterodonta and the sister group relationship of Acanthocardia and
      Venerupis. Monophyletic Bivalvia are resolved only by a Bayesian inference of the
      nucleotide data set. In all other analyses the two unionid species, being to only
      ones with genes located on both strands, do not group with the remaining
      bivalves. CONCLUSION: The two mt-genomes reported here add to and underline the
      high variability of gene order and presence of duplications in bivalve and
      molluscan taxa. Some genomic traits like the loss of the atp8 gene or the
      encoding of all genes on the same strand are homoplastic among the Bivalvia.
      These characters, gene order, and the nucleotide sequence data show considerable
      potential of resolving phylogenetic patterns at lower taxonomic levels.

PMID- 16948843
TI  - Two-dimensional gel proteome reference map of blood monocytes.
AB  - BACKGROUND: Blood monocytes play a central role in regulating host inflammatory
      processes through chemotaxis, phagocytosis, and cytokine production. However, the
      molecular details underlying these diverse functions are not completely
      understood. Understanding the proteomes of blood monocytes will provide new
      insights into their biological role in health and diseases. RESULTS: In this
      study, monocytes were isolated from five healthy donors. Whole monocyte lysates
      from each donor were then analyzed by 2D gel electrophoresis, and proteins were
      detected using Sypro Ruby fluorescence and then examined for phosphoproteomes
      using ProQ phospho-protein fluorescence dye. Between 1525 and 1769 protein spots
      on each 2D gel were matched, analyzed, and quantified. Abundant protein spots
      were then subjected to analysis by mass spectrometry. This report describes the
      protein identities of 231 monocyte protein spots, which represent 164 distinct
      proteins and their respective isoforms or subunits. Some of these proteins had
      not been previously characterized at the protein level in monocytes. Among the
      231 protein spots, 19 proteins revealed distinct modification by protein
      phosphorylation. CONCLUSION: The results of this study offer the most detailed
      monocyte proteomic database to date and provide new perspectives into the study
      of monocyte biology.

PMID- 16948844
TI  - PhyloPat: phylogenetic pattern analysis of eukaryotic genes.
AB  - BACKGROUND: Phylogenetic patterns show the presence or absence of certain genes
      or proteins in a set of species. They can also be used to determine sets of genes
      or proteins that occur only in certain evolutionary branches. Phylogenetic
      patterns analysis has routinely been applied to protein databases such as COG and
      OrthoMCL, but not upon gene databases. Here we present a tool named PhyloPat
      which allows the complete Ensembl gene database to be queried using phylogenetic
      patterns. DESCRIPTION: PhyloPat is an easy-to-use webserver, which can be used to
      query the orthologies of all complete genomes within the EnsMart database using
      phylogenetic patterns. This enables the determination of sets of genes that occur
      only in certain evolutionary branches or even single species. We found in total
      446,825 genes and 3,164,088 orthologous relationships within the EnsMart v40
      database. We used a single linkage clustering algorithm to create 147,922
      phylogenetic lineages, using every one of the orthologies provided by Ensembl.
      PhyloPat provides the possibility of querying with either binary phylogenetic
      patterns (created by checkboxes) or regular expressions. Specific branches of a
      phylogenetic tree of the 21 included species can be selected to create a branch
      specific phylogenetic pattern. Users can also input a list of Ensembl or EMBL IDs
      to check which phylogenetic lineage any gene belongs to. The output can be saved
      in HTML, Excel or plain text format for further analysis. A link to the FatiGO
      web interface has been incorporated in the HTML output, creating easy access to
      functional information. Finally, lists of omnipresent, polypresent and
      oligopresent genes have been included. CONCLUSION: PhyloPat is the first tool to
      combine complete genome information with phylogenetic pattern querying. Since we
      used the orthologies generated by the accurate pipeline of Ensembl, the obtained
      phylogenetic lineages are reliable. The completeness and reliability of these
      phylogenetic lineages will further increase with the addition of newly found
      orthologous relationships within each new Ensembl release.

PMID- 16948845
TI  - Circulating viral core and E1 antigen levels as supplemental markers for HCV
      chronic hepatitis.
AB  - The performance of polyclonal monospecific rabbit anti-sera raised against
      synthetic peptides derived from conserved HCV sequences of genotype 4 was
      evaluated for efficient detection of viral core and E1 antigens in circulating
      immune complexes (ICs) precipitated from 65 serum samples of HCV patients. The
      infection was established in those patients by the presence of HCV RNA in their
      sera. A novel enzyme-linked immunosorbent assay (ELISA) was developed for the
      detection of HCV core and E1 antigen in serum samples. Western blot analyses were
      used to demonstrate the presence of the core and E1 target antigen in serum
      samples. The mean OD readings of both core and E1 antigens were significantly
      higher (P < 0.05) among the viremic patients when compared to controls. Also a
      significant positive correlation (P < 0.05, r = 0.98) between the values of both
      core and E1 was recorded. Western blot analysis based on monospecific antibodies
      against core and E1 recognized the 38-kDa and 88 -kDa bands respectively in the
      sera of all infected patients. No specific reaction was observed with the sera
      from uninfected individuals. Interestingly the results of core and E1 antigen
      levels displayed no positive correlation with the HCV copy number as measured by
      bDNA. Liver enzymes (ALT and AST) showed a moderate positive correlation (r =
      0.44 and 0.47 respectively) with the viral core antigens level. The same trend
      holds true for E1 (r = 0.43 and 0.64 for ALT and AST respectively). HCV load in
      infected patients revealed extremely poor correlation with serum ALT and AST
      levels (r = 0.022 and 0.002 respectively). In conclusion we present a new
      combination of serological tools correlating with liver enzyme levels that could
      be utilized as supplemental tests to viral load testing. Also, a sensitive and
      specific immunoassay was developed for the detection of HCV core and E1 in human
      serum. This test can be applied for laboratory diagnosis of HCV infection.

PMID- 16948846
TI  - Natural products that reduce rotavirus infectivity identified by a cell-based
      moderate-throughput screening assay.
AB  - BACKGROUND: There is widespread interest in the use of innate immune modulators
      as a defense strategy against infectious pathogens. Using rotavirus as a model
      system, we developed a cell-based, moderate-throughput screening (MTS) assay to
      identify compounds that reduce rotavirus infectivity in vitro, toward a long-term
      goal of discovering immunomodulatory agents that enhance innate responses to
      viral infection. RESULTS: A natural product library consisting of 280 compounds
      was screened in the assay and 15 compounds that significantly reduced infectivity
      without cytotoxicity were identified. Time course analysis of four compounds with
      previously characterized effects on inflammatory gene expression inhibited
      replication with pre-treatment times as minimal as 2 hours. Two of these four
      compounds, alpha-mangostin and 18-beta-glycyrrhetinic acid, activated NFkappaB
      and induced IL-8 secretion. The assay is adaptable to other virus systems, and
      amenable to full automation and adaptation to a high-throughput format.
      CONCLUSION: Identification of several compounds with known effects on
      inflammatory and antiviral gene expression that confer resistance to rotavirus
      infection in vitro suggests the assay is an appropriate platform for discovery of
      compounds with potential to amplify innate antiviral responses.

PMID- 16948847
TI  - Development and validation of a bovine macrophage specific cDNA microarray.
AB  - BACKGROUND: The response of macrophages to danger signals is an important early
      stage in the immune response. Our understanding of this complex event has been
      furthered by microarray analysis, which allows the simultaneous investigation of
      the expression of large numbers of genes. However, the microarray resources
      available to study these events in livestock animals are limited. RESULTS: Here
      we report the development of a bovine macrophage specific (BoMP) cDNA microarray.
      The BoMP microarray contains 5026 sequence elements (printed in duplicate) and
      numerous controls. The majority of the clones incorporated on the microarray were
      derived from the BoMP cDNA library generated from bovine myeloid cells subjected
      to various stimuli, including over 900 sequences unique to the library.
      Additional clones representing immunologically important genes have been included
      on the BoMP microarray. The microarray was validated by investigating the
      response of bovine monocytes to stimulation with interferon-gamma and
      lipopolysaccharide using amplified RNA. At 2 and 16 hours post stimulation 695
      genes exhibited statistically significant differential expression, including; 26
      sequences unique to the BoMP library, interleukin 6, prion protein and toll-like
      receptor 4. CONCLUSION: A 5 K cDNA microarray has been successfully developed to
      investigate gene expression in bovine myeloid cells. The BoMP microarray is
      available from the ARK-Genomics Centre for Functional Genomics in Farm Animals,
      UK.

PMID- 16948848
TI  - Presynaptic regulation of the inhibitory transmission by GluR5-containing kainate
      receptors in spinal substantia gelatinosa.
AB  - GluR5-containing kainate receptors (KARs) are known to be involved in nociceptive
      transmission. Our previous work has shown that the activation of presynaptic KARs
      regulates GABAergic and glycinergic synaptic transmission in cultured dorsal horn
      neurons. However, the role of GluR5-containing KARs in the modulation of
      inhibitory transmission in the spinal substantia gelatinosa (SG) in slices
      remains unknown. In the present study, pharmacological, electrophysiological and
      genetic methods were used to show that presynaptic GluR5 KARs are involved in the
      modulation of inhibitory transmission in the SG of spinal slices in vitro. The
      GluR5 selective agonist, ATPA, facilitated the frequency but not amplitude of
      spontaneous inhibitory postsynaptic currents (sIPSCs) in SG neurons. ATPA
      increased sIPSC frequency in all neurons with different firing patterns as
      delayed, tonic, initial and single spike patterns. The frequency of either
      GABAergic or glycinergic sIPSCs was significantly increased by ATPA. ATPA could
      also induce inward currents in all SG neurons recorded. The frequency, but not
      amplitude, of action potential-independent miniature IPSCs (mIPSCs) was also
      facilitated by ATPA in a concentration-dependent manner. However, the effect of
      ATPA on the frequency of either sIPSCs or mIPSCs was abolished in GluR5-/- mice.
      Deletion of the GluR5 subunit gene had no effect on the frequency or amplitude of
      mIPSCs in SG neurons. However, GluR5 antagonist LY293558 reversibly inhibited
      sIPSC and mIPSC frequencies in spinal SG neurons. Taken together, these results
      suggest that GluR5 KARs, which may be located at presynaptic terminals,
      contribute to the modulation of inhibitory transmission in the SG. GluR5
      containing KARs are thus important for spinal sensory transmission/modulation in
      the spinal cord.

PMID- 16948849
TI  - The evaluation of the factors that cause aggregation during recombinant
      expression in E. coli is simplified by the employment of an aggregation-sensitive
      reporter.
AB  - BACKGROUND: The yields of soluble recombinant proteins expressed in bacteria are
      often low due to the tendency of the heterologous proteins to form aggregates.
      Therefore, aggregation reporters have been envisaged to simplify the comparison
      among different expression conditions and to speed up the identification of
      suitable protocols that improve the solubility. The probe we used is composed by
      an IbpAB promoter specifically activated by protein aggregates fused to a
      sequence coding the beta-galactosidase, the activity of which becomes, therefore,
      indicative of the aggregation degree. RESULTS: The collected data show that the
      probe is reliable in terms of reproducibility inside a range of experimental
      conditions and faster and more sensitive than the analysis methods based on SDS
      PAGE and successive western blot. The beta-galactosidase probe was useful to
      identify which parameters could influence the aggregation of the model proteins
      and to set up an optimized expression protocol. The effect of growth temperature,
      induction modality, co-expression with molecular chaperones and addition of
      osmolytes on the accumulation of aggregates were evaluated following the beta
      galactosidase activity. Interestingly, a significant correlation was observed
      between estimated decreased aggregation and higher yields of soluble protein. We
      also compared a set of expression vectors with various regulative features and
      found that the single characteristics, like promoter, copy number or polymerase,
      were not relevant for controlling the recombinant protein aggregation whilst the
      crucial factor resulted being the total expression rate of the system.
      CONCLUSION: The aggregation reporter used in our experiments represents a useful
      tool to evaluate the different factors that can be modulated to optimize a
      recombinant expression protocol. Furthermore, the rapid estimation of the
      aggregation degree enables to discriminate this from other causes responsible for
      scarce recombinant yields.

PMID- 16948850
TI  - Resistance to ursodeoxycholic acid-induced growth arrest can also result in
      resistance to deoxycholic acid-induced apoptosis and increased tumorgenicity.
AB  - BACKGROUND: There is a large body of evidence which suggests that bile acids
      increase the risk of colon cancer and act as tumor promoters, however, the
      mechanism(s) of bile acids mediated tumorigenesis is not clear. Previously we
      showed that deoxycholic acid (DCA), a tumorogenic bile acid, and ursodeoxycholic
      acid (UDCA), a putative chemopreventive agent, exhibited distinct biological
      effects, yet appeared to act on some of the same signaling molecules. The present
      study was carried out to determine whether there is overlap in signaling pathways
      activated by tumorogenic bile acid DCA and chemopreventive bile acid UDCA.
      METHODS: To determine whether there was an overlap in activation of signaling
      pathways by DCA and UDCA, we mutagenized HCT116 cells and then isolated cell
      lines resistant to UDCA induced growth arrest. These lines were then tested for
      their response to DCA induced apoptosis. RESULTS: We found that a majority of the
      cell lines resistant to UDCA-induced growth arrest were also resistant to DCA
      induced apoptosis, implying an overlap in DCA and UDCA mediated signaling.
      Moreover, the cell lines which were the most resistant to DCA-induced apoptosis
      also exhibited a greater capacity for anchorage independent growth. CONCLUSION:
      We conclude that UDCA and DCA have overlapping signaling activities and that
      disregulation of these pathways can lead to a more advanced neoplastic phenotype.

PMID- 16948851
TI  - Analysis of the genome-wide variations among multiple strains of the plant
      pathogenic bacterium Xylella fastidiosa.
AB  - BACKGROUND: The Gram-negative, xylem-limited phytopathogenic bacterium Xylella
      fastidiosa is responsible for causing economically important diseases in
      grapevine, citrus and many other plant species. Despite its economic impact,
      relatively little is known about the genomic variations among strains isolated
      from different hosts and their influence on the population genetics of this
      pathogen. With the availability of genome sequence information for four strains,
      it is now possible to perform genome-wide analyses to identify and categorize
      such DNA variations and to understand their influence on strain functional
      divergence. RESULTS: There are 1,579 genes and 194 non-coding homologous
      sequences present in the genomes of all four strains, representing a 76. 2%
      conservation of the sequenced genome. About 60% of the X. fastidiosa unique
      sequences exist as tandem gene clusters of 6 or more genes. Multiple alignments
      identified 12,754 SNPs and 14,449 INDELs in the 1528 common genes and 20,779 SNPs
      and 10,075 INDELs in the 194 non-coding sequences. The average SNP frequency was
      1.08 x 10(-2) per base pair of DNA and the average INDEL frequency was 2.06 x 10(
      2) per base pair of DNA. On an average, 60.33% of the SNPs were synonymous type
      while 39.67% were non-synonymous type. The mutation frequency, primarily in the
      form of external INDELs was the main type of sequence variation. The relative
      similarity between the strains was discussed according to the INDEL and SNP
      differences. The number of genes unique to each strain were 60 (9a5c), 54
      (Dixon), 83 (Ann1) and 9 (Temecula-1). A sub-set of the strain specific genes
      showed significant differences in terms of their codon usage and GC composition
      from the native genes suggesting their xenologous origin. Tandem repeat analysis
      of the genomic sequences of the four strains identified associations of repeat
      sequences with hypothetical and phage related functions. CONCLUSION: INDELs and
      strain specific genes have been identified as the main source of variations among
      strains, with individual strains showing different rates of genome evolution.
      Based on these genome comparisons, it appears that the Pierce's disease strain
      Temecula-1 genome represents the ancestral genome of the X. fastidiosa. Results
      of this analysis are publicly available in the form of a web database.

PMID- 16948852
TI  - Predictors of early death in a cohort of Ethiopian patients treated with HAART.
AB  - BACKGROUND: HAART has improved the survival of HIV infected patients. However,
      compared to patients in high-income countries, patients in resource-poor
      countries have higher mortality rates. Our objective was to identify independent
      risk factors for death in Ethiopian patients treated with HAART. METHODS: In a
      district hospital in Ethiopia, we treated adult HIV infected patients with HAART
      based on clinical and total lymphocyte count (TLC) criteria. We measured body
      weight and complete blood cell count at baseline, 4 weeks later, then repeated
      weight every month and complete blood cell count every 12 weeks. Time to death
      was the main outcome variable. We used the Kaplan Meier and Cox regression
      survival analyses to identify prognostic markers. Also, we calculated mortality
      rates for the different phases of the follow-up. RESULTS: Out of 162 recruited,
      152 treatment-naive patients contributed 144.1 person-years of observation (PYO).
      86 (57%) of them were men and their median age was 32 years. 24 patients died,
      making the overall mortality rate 16.7 per 100 PYO. The highest death rate
      occurred in the first month of treatment. Compared to the first month, mortality
      declined by 9-fold after the 18th week of follow-up. Being in WHO clinical stage
      IV and having TLC< or = 750/mcL were independent predictors of death. Haemoglobin
      (HGB) < or = 10 g/dl and TLC<= 1200/mcL at baseline were not associated with
      increased mortality. Body mass index (BMI) < or = 18.5 kg/m2 at baseline was
      associated with death in univariate analysis. Weight loss was seen in about a
      third of patients who survived up to the fourth week, and it was associated with
      increased death. Decline in TLC, HGB and BMI was associated with death in
      univariate analysis only. CONCLUSION: The high mortality rate seen in this cohort
      was associated with advanced disease stage and very low TLC at presentation.
      Patients should be identified and treated before they progress to advanced
      stages. The underlying causes for early death in patients presenting at late
      stages should be investigated.

PMID- 16948853
TI  - Protocol design and current status of CLIVIT: a randomized controlled multicenter
      relevance trial comparing clips versus ligatures in thyroid surgery.
AB  - BACKGROUND: Annually, more than 90000 surgical procedures of the thyroid gland
      are performed in Germany. Strategies aimed at reducing the duration of the
      surgical procedure are relevant to patients and the health care system especially
      in the context of reducing costs. However, new techniques for quick and safe
      hemostasis have to be tested in clinically relevance randomized controlled trials
      before a general recommendation can be given. The current standard for occlusion
      of blood vessels in thyroid surgery is ligatures. Vascular clips may be a safe
      alternative but have not been investigated in a large RCT. METHODS/DESIGN: CLIVIT
      (Clips versus Ligatures in Thyroid Surgery) is an investigator initiated,
      multicenter, patient-blinded, two-group parallel relevance randomized controlled
      trial designed by the Study Center of the German Surgical Society. Patients
      scheduled for elective resection of at least two third of the gland for benign
      thyroid disease are eligible for participation. After surgical exploration
      patients are randomized intraoperatively into either the conventional ligature
      group, or into the clip group. The primary objective is to test for a relevant
      reduction in operating time (at least 15 min) when using the clip technique.
      Since April 2004, 121 of the totally required 420 patients were randomized in
      five centers. DISCUSSION: As in all trials the different forms of bias have to be
      considered, and as in this case, a surgical trial, the role of surgical expertise
      plays a key role, and will be documented and analyzed separately. This is the
      first randomized controlled multicenter relevance trial to compare different
      vessel occlusion techniques in thyroid surgery with adequate power and other
      detailed information about the design as well as framework. If significant, the
      results might be generalized and may change the current surgical practice.

PMID- 16948854
TI  - Using GIS in a first national mapping of functional disability among older
      American Indians and Alaska Natives from the 2000 census.
AB  - BACKGROUND: Geographical information systems (GIS) have been used mainly in
      understanding infectious diseases and environmental threats in health research.
      Here, GIS was used to examine patterns of functional disability as one impact of
      chronic disease in American Indians and Alaska Natives. The study purpose was to
      create the first national mapping of functional disability for AIANs using the
      2000 U.S. Census. RESULTS: American Indians and Alaska Natives over age 65
      reported disability at a rate of 57.6% versus 41.9% for all people over 65 (P <
      or = 0.0001). Regional differences in levels and type of disability were evident.
      CONCLUSION: Maps help visualize those who might otherwise be 'lost' from the
      data. The significance of this study is that gerontologic programs and policies
      are data-driven, yet there is a lack of reliable national level data from US
      health systems on functional disability among American Indians and Alaska
      Natives. One study limitation was that Census questions regarding disability
      differed from traditional measures of activities of daily living and instrumental
      activities of daily living. An immediate policy recommendation would be to
      incorporate standard activities of daily living and instrumental activities of
      daily living language into future Census for a comprehensive, linked database for
      the future.

PMID- 16948855
TI  - Awareness and practice of patient's rights law in Lithuania.
AB  - BACKGROUND: Patient's rights law is intended to secure good medical practice, but
      it can also serve to improve understanding between patients and medical staff if
      both were aware of their rights. METHODS: Awareness and practice of the new
      patient's rights law in Lithuanian health care institutions was explored through
      a survey of 255 medical staff and 451 patients in the four Kaunas city medical
      units in 2002. Participation rates were 74% and 66%, respectively. RESULTS:
      Majority of the medical staff (85%) and little over one half of the patients
      (56%) had heard or read about the Law on Patient's Rights (p < 0.001). Only 50%
      of professionals compared to 69% of patients thought information for patients
      about diagnosis, treatment results and alternative treatments is necessary (p <
      0.001). A clear discrepancy was indicated between physicians informing the
      patients (80%-98% of physicians) and patients actually knowing (37%-54%) their
      treatment prognosis, disease complications or possible alternative treatment
      methods. CONCLUSION: These results suggest a need for awareness-raising among
      patients to improve the practical implementation of the Patient's Rights Law in
      Lithuania.

PMID- 16948857
TI  - Case report: Metaplastic carcinoma presenting as a breast abscess.
AB  - Metaplastic breast carcinoma (MBC) is a rare neoplasm containing a mixture of
      epithelial and mesenchymal elements. The epithelial component is usually ductal
      carcinoma but may include other variants of breast carcinomas including squamous
      carcinoma and osteogenic sarcoma. There is a relative paucity of data regarding
      such tumours. Metaplastic carcinoma carries a prognosis not dissimilar to that of
      comparable ductal carcinoma. This is the case of a 57 year old patient with MBC
      presenting with a breast abscess. A thorough literature search has not revealed
      any previous reports of MBC presenting as a breast abscess.

PMID- 16948856
TI  - The effects of N-terminal insertion into VSV-G of an scFv peptide.
AB  - Recombinant retroviruses, including lentiviruses, are the most widely used
      vectors for both in vitro and in vivo stable gene transfer. However, the
      inability to selectively deliver transgenes into cells of interest limits the use
      of this technology. Due to its wide tropism, stability and ability to pseudotype
      a range of viral vectors, vesicular stomatitis virus G protein (VSV-G) is the
      most commonly used pseudotyping protein. Here, we attempted to engineer this
      protein for targeting purposes. Chimaeric VSV-G proteins were constructed by
      linking a cell-directing single-chain antibody (scFv) to its N-terminal. We show
      that the chimaeric VSV-G molecules can integrate into retroviral and lentiviral
      particles. HIV-1 particles pseudotyped with VSV-G linked to an scFv against human
      Major Histocompatibility Complex class I (MHC-I) bind strongly and specifically
      to human cells. Also, this novel molecule preferentially drives lentiviral
      transduction of human cells, although the titre is considerably lower that
      viruses pseudotyped with VSV-G. This is likely due to the inefficient fusion
      activity of the modified protein. To our knowledge, this is the first report
      where VSV-G was successfully engineered to include a large (253 amino acids)
      exogenous peptide and where attempts were made to change the infection profile of
      VSV-G pseudotyped vectors.

PMID- 16948858
TI  - Revealing divergent evolution, identifying circular permutations and detecting
      active-sites by protein structure comparison.
AB  - BACKGROUND: Protein structure comparison is one of the most important problems in
      computational biology and plays a key role in protein structure prediction, fold
      family classification, motif finding, phylogenetic tree reconstruction and
      protein docking. RESULTS: We propose a novel method to compare the protein
      structures in an accurate and efficient manner. Such a method can be used to not
      only reveal divergent evolution, but also identify circular permutations and
      further detect active-sites. Specifically, we define the structure alignment as a
      multi-objective optimization problem, i.e., maximizing the number of aligned
      atoms and minimizing their root mean square distance. By controlling a single
      distance-related parameter, theoretically we can obtain a variety of optimal
      alignments corresponding to different optimal matching patterns, i.e., from a
      large matching portion to a small matching portion. The number of variables in
      our algorithm increases with the number of atoms of protein pairs in almost a
      linear manner. In addition to solid theoretical background, numerical experiments
      demonstrated significant improvement of our approach over the existing methods in
      terms of quality and efficiency. In particular, we show that divergent evolution,
      circular permutations and active-sites (or structural motifs) can be identified
      by our method. The software SAMO is available upon request from the authors, or
      from http://zhangroup.aporc.org/bioinfo/samo/ and http://intelligent.eic.osaka
      sandai.ac.jp/chenen/samo.htm. CONCLUSION: A novel formulation is proposed to
      accurately align protein structures in the framework of multi-objective
      optimization, based on a sequence order-independent strategy. A fast and accurate
      algorithm based on the bipartite matching algorithm is developed by exploiting
      the special features. Convergence of computation is shown in experiments and is
      also theoretically proven.

PMID- 16948859
TI  - Development of a Premature Stop Codon-detection method based on a bacterial two
      hybrid system.
AB  - BACKGROUND: The detection of Premature Stop Codons (PSCs) in human genes is very
      useful for the genetic diagnosis of different hereditary cancers, e.g. Familial
      Breast Cancer and Hereditary Non-Polyposis Colorectal Cancer (HNPCC). The
      products of these PSCs are truncated proteins, detectable in vitro by the Protein
      Truncation Test and in vivo by using the living translation machinery of yeast or
      bacteria. These living strategies are based on the construction of recombinant
      plasmids where the human sequence of interest is inserted upstream of a reporter
      gene. Although simple, these assays have their limitations. The yeast system
      requires extensive work to enhance its specificity, and the bacterial systems
      yield many false results due to translation re-initiation events occurring post
      PSCs. Our aim was to design a recombinant plasmid useful for detecting PSCs in
      human genes and resistant to bacterial translation re-initiation interferences.
      RESULTS: A functional recombinant plasmid (pREAL) was designed based on a
      bacterial two-hybrid system. In our design, the in vivo translation of fused
      fragments of the Bordetella pertussis adenylate cyclase triggers the production
      of cAMP giving rise to a selectable bacterial phenotype. When a gene of interest
      is inserted between the two fragments, any PSC inhibits the enzymatic activity of
      the product, and translation re-initiation events post-PSC yield separated
      inactive fragments. We demonstrated that the system can accurately detect PSCs in
      human genes by inserting mutated fragments of the brca1 and msh2 gene. Western
      Blot assays revealed translation re-initiation events in all the tested colonies,
      implying that a simpler plasmid would not be resistant to this source of false
      negative results. The application of the system to a HNPCC family with a nonsense
      mutation in the msh2 gene correctly diagnosed wild type homozygous and
      heterozygous patients. CONCLUSION: The developed pREAL is applicable to the
      detection of PSCs in human genes related to different diseases and is resistant
      to translation re-initiation events. The diagnosis steps are easy, have a low
      cost, detect only pathologic mutations, and allow the analysis of separated
      alleles.

PMID- 16948860
TI  - Expression of innate immune complement regulators on brain epithelial cells
      during human bacterial meningitis.
AB  - BACKGROUND: In meningitis, the cerebrospinal fluid contains high levels of innate
      immune molecules (e.g. complement) which are essential to ward off the infectious
      challenge and to promote the infiltration of phagocytes (neutrophils, monocytes).
      However, epithelial cells of either the ependymal layer, one of the established
      niche for adult neural stem cells, or of the choroid plexus may be extremely
      vulnerable to bystander attack by cytotoxic and cytolytic complement components.
      METHODS: In this study, we assessed the capacity of brain epithelial cells to
      express membrane-bound complement regulators (ie, CD35, CD46, CD55 and CD59) in
      vitro and in situ by immunostaining of control and meningitis human brain tissue
      sections. RESULTS: Double immunofluorescence experiments for ependymal cell
      markers (GFAP, S100, ZO-1, E-cadherin) and complement regulators indicated that
      the human ependymal cell line model was strongly positive for CD55, CD59 compared
      to weak stainings for CD46 and CD35. In tissues, we found that CD55 was weakly
      expressed in control choroid plexus and ependyma but was abundantly expressed in
      meningitis. Anti-CD59 stained both epithelia in apical location while increased
      CD59 staining was solely demonstrated in inflamed choroid plexus. CD46 and CD35
      were not detected in control tissue sections. Conversely, in meningitis, the
      ependyma, subependyma and choroid plexus epithelia were strongly stained for CD46
      and CD35. CONCLUSION: This study delineates for the first time the capacity of
      brain ependymal and epithelial cells to respond to and possibly sustain the
      innate complement-mediated inflammatory insult.

PMID- 16948861
TI  - The use of a Cissus quadrangularis formulation in the management of weight loss
      and metabolic syndrome.
AB  - AIM: Once considered a problem of developed countries, obesity and obesity
      related complications (such as metabolic syndrome) are rapidly spreading around
      the globe. The purpose of the present study was to investigate the use of a
      Cissus quadrangularis formulation in the management of metabolic syndrome,
      particularly weight loss and central obesity. METHODS: The study was a
      randomized, double-blind, placebo-controlled design involving 123 overweight and
      obese persons (47.2% male; 52.8% female; ages 19-50). The 92 obese (BMI >30)
      participants were randomized into three groups; placebo, formulation/no diet, and
      formulation/diet (2100-2200 calories/day). The 31 overweight participants (BMI =
      25-29) formed a fourth (no diet) treatment group. All participants received two
      daily doses of the formulation or placebo and remained on a normal or calorie
      controlled diet for 8 weeks. RESULTS: At the end of the trial period,
      statistically significant net reductions in weight and central obesity, as well
      as in fasting blood glucose, total cholesterol, LDL-cholesterol, triglycerides,
      and C-reactive protein were observed in participants who received the
      formulation, regardless of diet. CONCLUSION: Cissus quadrangularis formulation
      appears to be useful in the management of weight loss and metabolic syndrome.

PMID- 16948862
TI  - Induction of neutralising antibodies by virus-like particles harbouring surface
      proteins from highly pathogenic H5N1 and H7N1 influenza viruses.
AB  - There is an urgent need to develop novel approaches to vaccination against the
      emerging, highly pathogenic avian influenza viruses. Here, we engineered
      influenza viral-like particles (Flu-VLPs) derived from retroviral core particles
      that mimic the properties of the viral surface of two highly pathogenic influenza
      viruses of either H7N1 or H5N1 antigenic subtype. We demonstrate that, upon
      recovery of viral RNAs from a field strain, one can easily generate expression
      vectors that encode the HA, NA and M2 surface proteins of either virus and
      prepare high-titre Flu-VLPs. We characterise these Flu-VLPs incorporating the HA,
      NA and M2 proteins and we show that they induce high-titre neutralising
      antibodies in mice.

PMID- 16948863
TI  - Psychological process from hospitalization to death among uninformed terminal
      liver cancer patients in Japan.
AB  - BACKGROUND: Although the attitude among doctors toward disclosing a cancer
      diagnosis is becoming more positive, informing patients of their disease has not
      yet become a common practice in Japan. We examined the psychological process,
      from hospitalization until death, among uninformed terminal cancer patients in
      Japan, and developed a psychological model. METHODS: Terminal cancer patients
      hospitalized during the recruiting period voluntarily participated in in-depth
      interviews. The data were analyzed by grounded theory. RESULTS: Of the 87
      uninformed participants at the time of hospitalization, 67% (N = 59) died without
      being informed of their diagnosis. All were male, 51-66 years of age, and all
      experienced five psychological stages: anxiety and puzzlement, suspicion and
      denial, certainty, preparation, and acceptance. At the end of each stage, obvious
      and severe feelings were observed, which were called "gates." During the final
      acceptance stage, patients spent a peaceful time with family, even talking about
      their dreams with family members. CONCLUSION: Unlike in other studies, the
      uninformed patients in this study accepted death peacefully, with no exceptional
      cases. Despite several limitations, this study showed that almost 70% of the
      uninformed terminal cancer patients at hospitalization died without being
      informed, suggesting an urgent need for culturally specific and effective
      terminal care services for cancer patients in Japan.

PMID- 16948864
TI  - Cancer diagnosis marker extraction for soft tissue sarcomas based on gene
      expression profiling data by using projective adaptive resonance theory (PART)
      filtering method.
AB  - BACKGROUND: Recent advances in genome technologies have provided an excellent
      opportunity to determine the complete biological characteristics of neoplastic
      tissues, resulting in improved diagnosis and selection of treatment. To
      accomplish this objective, it is important to establish a sophisticated algorithm
      that can deal with large quantities of data such as gene expression profiles
      obtained by DNA microarray analysis. RESULTS: Previously, we developed the
      projective adaptive resonance theory (PART) filtering method as a gene filtering
      method. This is one of the clustering methods that can select specific genes for
      each subtype. In this study, we applied the PART filtering method to analyze
      microarray data that were obtained from soft tissue sarcoma (STS) patients for
      the extraction of subtype-specific genes. The performance of the filtering method
      was evaluated by comparison with other widely used methods, such as signal-to
      noise, significance analysis of microarrays, and nearest shrunken centroids. In
      addition, various combinations of filtering and modeling methods were used to
      extract essential subtype-specific genes. The combination of the PART filtering
      method and boosting--the PART-BFCS method--showed the highest accuracy. Seven
      genes among the 15 genes that are frequently selected by this method--MIF,
      CYFIP2, HSPCB, TIMP3, LDHA, ABR, and RGS3--are known prognostic marker genes for
      other tumors. These genes are candidate marker genes for the diagnosis of STS.
      Correlation analysis was performed to extract marker genes that were not selected
      by PART-BFCS. Sixteen genes among those extracted are also known prognostic
      marker genes for other tumors, and they could be candidate marker genes for the
      diagnosis of STS. CONCLUSION: The procedure that consisted of two steps, such as
      the PART-BFCS and the correlation analysis, was proposed. The results suggest
      that novel diagnostic and therapeutic targets for STS can be extracted by a
      procedure that includes the PART filtering method.

PMID- 16948865
TI  - The virion-associated incoming HIV-1 RNA genome is not targeted by RNA
      interference.
AB  - BACKGROUND: RNA interference (RNAi) has proven to be a powerful tool to suppress
      gene expression and can be used as a therapeutic strategy against human
      pathogenic viruses such as human immunodeficiency virus type 1 (HIV-1).
      Theoretically, RNAi-mediated inhibition can occur at two points in the
      replication cycle, upon viral entry before reverse transcription of the RNA
      genome, and on the newly transcribed viral RNA transcripts. There have been
      conflicting results on whether RNAi can target the RNA genome of infecting HIV-1
      particles. We have addressed this issue with HIV-1-based lentiviral vectors.
      RESULTS: We determined the transduction efficiency of a lentiviral vector, as
      measured by GFP expressing cells, which reflects the number of successful
      integration events in a cell line stably expressing shNef. We did not observe a
      difference in the transduction efficiency comparing lentiviral vectors with or
      without the Nef target sequence in their genome. The results were similar with
      particles pseudotyped with either the VSV-G or HIV-1 envelope. Additionally, no
      reduced transduction efficiencies were observed with multiple other shRNAs
      targeting the vector genome or with synthetic siNef when transiently transfected
      prior to transduction. CONCLUSION: Our findings indicate that the incoming HIV-1
      RNA genome is not targeted by RNAi, probably due to inaccessibility to the RNAi
      machinery. Thus, therapeutic RNAi strategies aimed at preventing proviral
      integration should be targeting cellular receptors or co-factors involved in pre
      integration events.

PMID- 16948866
TI  - Metabolic labeling of plant cell cultures with K(15)NO3 as a tool for
      quantitative analysis of proteins and metabolites.
AB  - Strategies for robust quantitative comparison between different biological
      samples are of high importance in experiments that address biological questions
      beyond the establishment of protein lists. Here, we propose the use of 15N-KNO3
      as the only nitrogen source in Arabidopsis cell cultures in order to achieve a
      metabolically fully labeled cell population. Proteins from such metabolically
      labeled culture are distinguishable from unlabeled protein populations by a
      characteristic mass shift that depends on the amino acid composition of the
      tryptic peptide analyzed. In addition, the metabolically labeled cell extracts
      are also suitable for comparative quantitative analysis of nitrogen-containing
      cellular metabolic complement. Protein extracts from unlabeled and from
      standardized 15N-labeled cells were combined into one sample for joined
      analytical processing. This has the advantage of (i) reduced experimental
      variability and (ii) immediate relative quantitation at the level of single
      extracted peptide and metabolite spectra. Together ease and accuracy of relative
      quantitation for profiling experiments is substantially improved. The metabolic
      labeling strategy has been validated by mixtures of protein extracts and
      metabolite extracts from the same cell cultures in known ratios of labeled to
      unlabeled extracts (1:1, 1:4, and 4:1). We conclude that saturating metabolic 15N
      labeling provides a robust and affordable integrative strategy to answer
      questions in quantitative proteomics and nitrogen focused metabolomics.

PMID- 16948867
TI  - HLA-A24 and survivin: possibilities in therapeutic vaccination against cancer.
AB  - Recently, it was described that an HLA-A24 restricted peptide derived from the
      survivin splice variant survivin-2B can be recognized by CD8+ cytotoxic T-cells.
      The identification of an HLA-A24 epitope is critical for survivin-based
      immunotherapy as HLA-24 is the most frequent HLA allele in Asia. Consequently,
      this survivin-2B epitope is already a target in a clinical study in patients with
      advanced or recurrent colorectal cancer expressing survivin. However, the splice
      variant survivin-2B has been described to be pro-apoptotic, and is only expressed
      at low levels in most malignant tissues. Furthermore, survivin-2B expression are
      significantly decreased in later tumor stages and inversely correlated with tumor
      differentiation and invasion. Consequently, survivin is a more general
      vaccination candidate than the splice variant survivin-2B. Here, we on the basis
      of spontaneous immune responses in HLA-A24+ cancer patients describes that a HLA
      A24-restricted survivin epitopes does indeed exist. Consequently, this epitope is
      an attractive target for the ongoing survivin-based peptide immunotherapy against
      cancer.

PMID- 16948872
TI  - The invariant surface glycoprotein ISG75 gene family consists of two main groups
      in the Trypanozoon subgenus.
AB  - In Trypanosoma brucei brucei, an invariant surface glycoprotein of molecular
      weight 75 kDa (ISG75) is uniformly distributed over the surface of a trypanosome
      and is specific for bloodstream-form parasites. For the other taxa of the
      Trypanozoon subgenus no data about this surface molecule are available.
      Therefore, we investigated the ISG75 in the genomes of several pathogenic
      Trypanozoon by Southern blot, PCR and RT-PCR and sequence analysis. This study
      reveals that (i) all members of the Trypanozoon subgenus, i.e. T. b. brucei, T.
      b. gambiense, T. b. rhodesiense, T. evansi and T. equiperdum, harbour ISG75 as
      multiple gene copies with at least 4-16 copies per genome; (ii) ISG75 gDNA and
      cDNA sequences are distributed in 2 groups that share at least 75% and 77%
      identity respectively; (iii) sequences from both groups are transcribed in all
      species and subspecies of the Trypanozoon subgenus; (iv) the main differences
      between group I and group II are located in the variable region at the amino
      terminus of the putative proteins; (v) however, all the sequences in both groups
      have some well-conserved features, such as the cysteine residues, an amino
      terminal cleavable signal peptide, a single alpha-helix transmembrane domain and
      a cytoplasmic domain at the carboxy-terminus.

PMID- 16948873
TI  - Transmission of Tetracapsuloides bryosalmonae (Myxozoa: Malacosporea), the
      causative organism of salmonid proliferative kidney disease, to the freshwater
      bryozoan Fredericella sultana.
AB  - Proliferative kidney disease (PKD), caused by the malacosporean parasite
      Tetracapsuloides bryosalmonae, causes significant losses among salmonids in
      Western Europe and North America. The role of salmonid fish in the life-cycle of
      this parasite has been conjectured upon for over a quarter of a century. To
      examine whether fish can transmit the infection to bryozoans, the known
      invertebrate host, water containing parasitized brown trout Salmo trutta was
      pumped into tanks containing colonies of Fredericella sultana collected from the
      wild. The specific parasite-free status of these colonies being first assessed,
      by PCR and prolonged laboratory culture. After 6 weeks exposure to the brown
      trout aquarium effluent, portions of these colonies displayed overt infections
      with T. bryosalmonae. This was in contrast to control bryozoans, derived from the
      experimental colonies prior to exposure, which remained T. bryosalmonae negative.
      In addition, spores obtained from the experimentally infected colonies were
      exposed to naive rainbow trout, resulting in clinical PKD, thus completing a
      cycle of transmission. During the experiments, the infection was noted to inhibit
      statoblast formation within bryozoans and appeared to be pathogenic, finally
      killing the bryozoan host. These findings indicate that fish can transmit the
      parasite to bryozoans and are an integral part of this parasite's life-cycle.

PMID- 16948874
TI  - Sensitive measure of prevalence and parasitaemia of haemosporidia from European
      blackbird (Turdus merula) populations: value of PCR-RFLP and quantitative PCR.
AB  - Haemosporidian parasites are common in birds in which they act as an important
      selective pressure. While most studies so far have focused on the effect of their
      prevalence on host life-history traits, no study has measured the effect of
      parasitaemia. We developed molecular methods to detect, identify and quantify
      haemosporidia in 2 natural populations of the Blackbird Turdus merula. Three
      different parasite genotypes were found - 1 Haemoproteus and 2 Plasmodium. A PCR
      RFLP screening revealed that only approximately 3% of blackbirds were free of
      parasites, compared to the 34% of uninfected birds estimated by blood smear
      screening. A quantitative PCR (q-PCR) assay revealed a weaker parasitaemia in
      microscopically undetected parasites compared to microscopically detected ones.
      Large parasitaemia differences were found between parasite species, suggesting
      either differing parasite life-histories or host resistance. Parasitaemias were
      also weaker in male hosts, and in urban habitats, suggesting that both host
      factors (e.g. immunity) and habitat characteristics (e.g. vector availability)
      may modulate parasite density. Interestingly, these differences in parasitaemia
      were comparable to differences in parasite prevalence estimated by smear
      screening. This suggests that previous results obtained by smear screening should
      be reinterpreted in terms of parasitaemia instead of parasite prevalence.

PMID- 16948875
TI  - Further evaluation of the synthetic peptide vaccine S3Pvac against Taenia solium
      cysticercosis in pigs in an endemic town of Mexico.
AB  - Taenia solium cysticercosis is a parasitic disease frequently affecting human
      health and the pig industry in many developing countries. A synthetic peptide
      vaccine (designated S3Pvac) against porcine cysticercosis has been developed
      previously as an aid to interrupt transmission and has been shown to be
      effective. The results of the present study support the effectiveness of the
      vaccine under endemic field conditions. However, given the time-frame of the
      vaccination trial, no changes in the local levels of transmission were detectable
      before and after vaccination using sentinel pigs. Thus, this investigation shows
      the limited usefulness of single vaccination as the sole means of interrupting
      Taenia solium transmission in an endemic region.

PMID- 16948876
TI  - Eimeria-parasites are associated with a lowered mother's and offspring's body
      condition in island and mainland populations of the bank vole.
AB  - This study, based on correlative data, tests the hypothesis that infections with
      Eimeria spp. parasites exert a significant loss of fitness of bank voles
      (Clethrionomys glareolus) reflected in lower reproductive success and survival,
      declining host population densities and are associated positively with population
      size. The study was conducted in 20 mainland and 27 island populations in central
      Finland during May-September in 1999. Faecal samples showed that 28% of 767
      individuals were infected with Eimeria spp. The presence of Eimeria parasites was
      higher in dense mainland populations than in sparsely populated islands. Eimerian
      infections increased during the course of the breeding season, probably as a
      result of the high infection rate of young individuals. Accordingly, the body
      masses of bank voles were negatively related to the presence of Eimeria spp.
      Reproductive output, as measured by the breeding probability of females and
      litter size, was not associated with the presence of eimerian infection.
      Interestingly, the body condition of the infected mothers appeared to be low.
      Moreover, mother's body condition was the single most important variable studied
      that showed a positive correlation to pup's body condition at birth. On small
      islands (< or =3.2 ha) that were comprehensively trapped, the mean number of
      Eimeria spp. in the bank vole population was negatively related to density
      changes of the bank vole population during the study. Our data are consistent
      with the idea that infection with coccidian parasites may be one of the factors
      responsible for declining host populations in small, isolated populations.

PMID- 16948877
TI  - Within-host dynamics of an intestinal pathogen of bumble bees.
AB  - The success of a pathogen depends not only on its transmission to new hosts, but
      also on its ability to colonize and persist within its current host. Studies of
      within-host dynamics have focused on only a few diseases of humans, whereas
      little is known about the factors that influence pathogen populations as they
      develop inside non-human hosts. Here, we investigate pathogen dynamics occurring
      within bumble bees (Bombus impatiens) infected by the gut trypanosome Crithidia
      bombi. Infection by C. bombi showed several features characteristic of vertebrate
      diseases, including a rapid initial increase in infection intensity, marked
      oscillations in parasitaemia, and the stimulation of a systemic immune response
      in infected bees. Within-host dynamics generated substantial variation in the
      infectiousness and flower-visiting behaviour of bumble bees. Changes in bee
      foraging that arise from infection may influence the probability of C. bombi
      transmission between bees at flowers.

PMID- 16948878
TI  - A scabies outbreak in a further education college in Gloucestershire.
AB  - Scabies outbreaks in England have been reported in hospitals, long-stay wards,
      acquired immune deficiency syndrome (AIDS) units and residential homes for the
      elderly. This paper describes the control of an outbreak in a further education
      college for persons with learning disabilities. In March 2004, four confirmed
      cases of scabies were reported among a subset of 108 students and 41 staff
      members. Staff had considerable physical contact with the students who were
      housed in five groups of homes, individual homes and support centres. Mass
      prophylaxis was offered to all staff and students, through 39 general practice
      surgeries. Challenges overcome were: ensuring complete case ascertainment,
      accessing of up-to-date information about students and staff, achieving a
      coordinated approach to treatment, securing informed consent and media
      management. No further outbreaks have been reported. The college has revised its
      information request form for new students.

PMID- 16948879
TI  - Physician shortage.

PMID- 16948880
TI  - The concept and trajectory of "operative competence" in surgical training.

PMID- 16948881
TI  - Value of preoperative serum CA 19-9 levels in predicting resectability for
      pancreatic cancer.
AB  - BACKGROUND: Pancreatic cancer carries a poor prognosis; at operation
      approximately 25% of patients will be found to have unresectable tumours even
      though CT has demonstrated that they are resectable. At our tertiary care centre,
      we wished to find out if there is an optimum cut-off value for the CA 19-9 level
      preoperatively that will indicate that the pancreatic cancer is unresectable
      despite radiologic imaging that suggests otherwise according to receiver
      operating characteristic (ROC) curve analysis. METHODS: Preoperative demographic
      data, clinical features and serum CA 19-9 levels were reviewed for 51 patients
      with pancreatic cancer who underwent laparotomy between 1998 and 2003.
      Preoperatively, resectability was determined from a complete history, physical
      examination and radiologic imaging. An ROC curve was constructed for the CA 19-9
      levels. The sensitivity, specificity, positive and negative predictive values of
      CA 19-9 were calculated with several cut-off points. RESULTS: There were 18 (36%)
      resectable and 33 (64%) unresectable pancreatic cancers. The mean CA 19-9 level
      was 68.8 U/mL in the resectable group and 622 U/mL in unresectable group. When a
      CA 19-9 level of 256.4 U/mL was used as a cutoff point, the specificity and
      sensitivity was 92.3% and 82.4% respectively. CONCLUSION: Preoperative CA 19-9
      levels may be a useful marker for determining preoperatively which patients have
      unresectable disease despite the demonstration on CT of resectable disease.

PMID- 16948882
TI  - High tibial osteotomy with use of the Taylor Spatial Frame external fixator for
      osteoarthritis of the knee.
AB  - BACKGROUND: High tibial osteotomy (HTO) is used to treat medial compartment
      osteoarthritis of the knee in active patients with varus alignment. In this study
      we review the clinical and radiographic outcomes associated with the Taylor
      Spatial Frame (Smith & Nephew), and its use in HTOs, and we include an
      illustrative case report. METHODS: In 7 patients with medial compartment
      osteoarthritis of the knee and varus alignment, the Taylor Spatial Frame was
      applied to the tibia in the operating room and a proximal tibial osteotomy was
      performed. Patients followed a computer-generated turning schedule until the
      desired correction was achieved. The frame was removed when the osteotomy site
      had healed. The lower extremity measure (LEM) was used to assess physical
      function. Clinical outcome measures relating to the Taylor Spatial Frame included
      latency, time to correction, time in the frame, number of residual corrections
      and complications. Radiographic outcomes included preoperative Resnick grades of
      osteoarthritis, pre- and post-correction limb alignment and tibial slope
      measurements. RESULTS: Average (and standard deviation) LEM grade at a mean 41
      (14) months follow-up after correction was 94% (5%). Average latency was 8 days,
      time to correction was 15 days, time in the frame was 23 weeks and number of
      residual corrections was 1.3. Complications were similar to those for external
      fixators. Radiographic correction goals were met in all patients. CONCLUSION: The
      Taylor Spatial Frame is a valuable asset when using HTO to treat medial
      compartment osteoarthritis of the knee.

PMID- 16948883
TI  - Influence of hospital characteristics on operative death and survival of patients
      after major cancer surgery in Ontario.
AB  - BACKGROUND: There is a lack of information from Canadian hospitals on the role of
      hospital characteristics such as procedure volume and teaching status on the
      survival of patients who undergo major cancer resection. Therefore, we chose to
      study these relationships using data from patients treated in Ontario hospitals.
      METHODS: We used the Ontario Cancer Registry from calendar years 1990-2000 to
      obtain data on patients who underwent surgery for breast, colon, lung or
      esophageal cancer or who underwent major liver surgery related to a cancer
      diagnosis between 1990 and 1995 in order to assess the influence of volume of
      procedures and teaching status of hospitals on in-hospital death rate and long
      term survival. For each disease site and before observing patient outcomes data,
      volume cut-off points were selected to create volume groups with similar numbers
      of patients. Teaching hospitals were those directly affiliated with a medical
      school. Logistic regression and proportional hazards models were used to consider
      the clustering of data at the hospital level and to assess operative death and
      long-term survival. We also used 4 measures to gauge the degree of procedure
      regionalization across the province including (1) the number of hospitals
      performing a procedure; (2) the percentage of patients treated in teaching
      hospitals; (3) the percentage of rural patients treated in higher volume
      procedure hospitals; and (4) median distances travelled by patients to receive
      care. RESULTS: The number of patients in our cohorts who underwent resection of
      the breast, colon, lung, esophagus or liver was 14 346, 8398, 2698, 629 and 362,
      respectively. Surgery in a high-volume versus a low-volume hospital did not have
      a statistically significant influence on the odds of operative death for patients
      who underwent colon, liver, lung or esophageal cancer resection. The risk of long
      term death was increased in low-volume versus high-volume hospitals for patients
      who underwent resection of the breast (hazard ratio [HR] 1.2, 95% confidence
      interval [95% CI] 1.0-1.4, p < 0.05), lung (HR 1.3, 95% CI 1.1-1.6, p < 0.01) and
      liver (HR 1.7, 95% CI 1.0-2.7, p = 0.04). There were no significant differences
      in the odds of operative (in-hospital) death or risk of long-term death among
      patients treated in teaching compared with nonteaching hospitals. There was more
      regionalization of liver, lung and esophageal operations versus breast and colon
      operations. CONCLUSIONS: Increased hospital procedure volume correlated with
      improved longterm survival for patients in Ontario who underwent some, but not
      all, cancer resections, whereas hospital teaching status had no significant
      impact on patient outcomes. Across the province, further regionalization of care
      may help improve the quality of some cancer procedures.

PMID- 16948884
TI  - Core competencies in surgery: evaluating the goals of urology residency training
      in Canada.
AB  - BACKGROUND: In Canada and the United States, the relevance and utility of
      training objectives as perceived by practising surgeons is rarely examined. We
      sought to determine if urology residency training objectives reflect the broad
      realities of urologic practice. METHODS: A survey, based on the Royal College of
      Physicians and Surgeons of Canada training objectives for urology, was designed
      and validated. All 418 full-time practising members of the Canadian Urological
      Association were surveyed. RESULTS: The overall response rate was 63%. Many
      specialized clinical areas of urology that receive little emphasis in the
      training objectives were rated as useful by the majority: laparoscopic surgery
      (92%), percutaneous renal access (86%), transrectal ultrasonography (84%),
      pediatric urology (81%), extracorporeal shockwave lithotripsy (70%), urethral
      reconstruction (66%) and adrenal surgery (62%). Microsurgery and transplantation
      were perceived as less useful (54% and 22% respectively). Virtually all
      nonsurgical training objectives were regarded as useful components of training;
      however, in the opinion of the majority of respondents residency did not prepare
      them for many of these: the challenges of office and hospital administration (91%
      and 89% not prepared [NP]), building a referral base (67% NP), time management
      (60% NP) and providing care under financial constraints (60% NP). CONCLUSION: The
      study results support the current training objectives and indicate areas
      requiring increased emphasis.

PMID- 16948885
TI  - Treatment of esophageal achalasia with Heller myotomy: retrospective evaluation
      of patient satisfaction and disease-specific quality of life.
AB  - BACKGROUND: Prospective randomized studies have suggested that surgery palliates
      esophageal achalasia more effectively than pneumatic dilatation, but for some
      dilatation is still the procedure of choice for initial treatment. We decided to
      compare achalasia symptoms before and after Heller myotomy by means of
      postoperative questionnaires. METHODS: The study included 22 patients who
      underwent Heller myotomy for achalasia at the Hotel Dieu Hospital, Queen's
      University, Kingston, Ont., since July 1990; 5 of them required repeat myotomy
      for symptom recurrence, for a total of 9 open and 18 laparoscopic procedures.
      Median follow-up was 43 (range 6-109) months. Preoperative and postoperative data
      regarding dysphagia, regurgitation, chest pain and overall patient satisfaction
      were gathered. Symptom scores were calculated by adding severity (0 = none, 2 =
      mild, 4 = moderate, 6 = severe) to frequency (0 = never, 1 = occasionally, 2 =
      once a month, 3 = every week, 4 = twice a week, 5 = daily). Patients having a
      repeat procedure were instructed to evaluate symptoms with respect to their
      initial myotomy. RESULTS: Seventeen (77%) patients were successfully contacted, 4
      of them had subsequent repeat myotomy for symptom recurrence. Initially, overall
      symptom scores decreased for all but 1 patient, with mean preoperative and
      postoperative values of 23.1 and 7.3 respectively (p < 0.001). The patient in
      whom symptoms did not improve is a candidate for a repeat procedure. Repeat
      myotomy was performed after a median of 38 (range 23-75) months, corresponding to
      an overall 3-year positive outcome in 13 (76%) of the 17 patients. Fifteen (88%)
      patients considered their myotomies a success and 16 (94%) would choose to have
      this procedure again given the outcome. CONCLUSION: Heller myotomy appears to be
      effective in alleviating the symptoms of achalasia. Repeat myotomy is
      occasionally required.

PMID- 16948886
TI  - Pediatric burns: the forgotten trauma of childhood.

PMID- 16948887
TI  - Wilfred Trotter: surgeon, philosopher.
AB  - There is no significant biography that records the accomplishments of Sir Wilfred
      Trotter, who was a general surgeon in its pure sense at a time when surgical
      specialization was in its infancy. Trotter was born in the 1870s in England.
      Despite being bedridden during his childhood with a musculoskeletal condition he
      was able to study medicine at London University, and eventually became Professor
      and Chair of Surgery at the University College Hospital, a position he held until
      his death in November 1939. He made many contributions to surgical care,
      particularly in the field of oncology. He attended to many famous people,
      including King George V and Sigmund Freud and was greatly honoured in his own
      milieu. He was named honorary surgeon and Sargent Surgeon to the king. In
      addition, he was a thoughtful individual who addressed problems in human
      behaviour, contradicting the stereotype of the contemporary surgeon.

PMID- 16948888
TI  - Gastrointestinal stromal tumour: varied presentation of a rare disease.

PMID- 16948889
TI  - Scapholunate interosseus ligament tears in elite gymnasts.

PMID- 16948890
TI  - Etanercept and infliximab for the treatment of psoriatic arthritis: a systematic
      review and economic evaluation.
AB  - OBJECTIVES: To evaluate the clinical effectiveness, safety, tolerability and cost
      effectiveness of etanercept and infliximab for the treatment of active and
      progressive psoriatic arthritis (PsA) in patients who have inadequate response to
      standard treatment, including disease-modifying antirheumatic drug (DMARD)
      therapy. DATA SOURCES: Electronic databases were searched up to July 2004. REVIEW
      METHODS: A systematic review evaluated the clinical efficacy and adverse effects
      of etanercept and infliximab. The efficacy of DMARDs in the treatment of PsA was
      also reviewed and treatments were compared using Bayesian evidence synthesis
      methods. Following evaluation of existing economic evaluations of etanercept and
      infliximab in PsA, a new economic model was developed (the York Model). This
      utilised the results from the evidence synthesis and data from a range of other
      sources. RESULTS: Across the two trials, at 12 weeks, around 65% of patients
      treated with etanercept achieved an American College of Rheumatology (ACR) 20
      {pooled relative risk (RR) 4.19 [95% confidence interval (CI) 2.74 to 6.42]},
      demonstrating a basic degree of efficacy in terms of arthritis-related symptoms.
      In addition, around 45% of patients treated with etanercept achieved an ACR 50
      [pooled RR 10.84 (95% CI 4.47 to 26.28)] and around 12% achieved an ACR 70
      [pooled RR 16.28 (95% CI 2.20 to 120.54)], demonstrating a good level of
      efficacy. The subgroup analyses conducted in one trial revealed that the effect
      of etanercept was not dependent upon patients' concomitant use of methotrexate.
      In addition, almost 85% of patients treated with etanercept achieved a Psoriatic
      Arthritis Response Criteria (PsARC) [pooled RR 2.60 (95% CI 1.96 to 3.45). The
      Psoriatic Area and Severity Index (PASI) results indicate some beneficial effect
      on psoriasis at 12 weeks; however, the data are sparse. The statistically
      significant reduction (improvement) in Health Assessment Questionnaire (HAQ)
      score with etanercept compared with placebo indicates a beneficial effect of
      etanercept on function. Similar results were seen at 24 weeks, except that the
      results for PASI 75 and PASI 50 now achieved statistical significance and data
      for Total Sharp Score annualised rate of progression were available; this was
      statistically significantly lower in etanercept-treated patients than in placebo
      treated patients. Uncontrolled follow-up of patients indicates that treatment
      benefit may be maintained for at least 50 weeks. At 16 weeks, 65% of patients
      treated with infliximab achieved an ACR 20 [RR 6.80 (95% CI 2.89 to 16.01)],
      demonstrating a basic degree of efficacy in terms of arthritis-related symptoms.
      This level of efficacy was not dependent upon patients' concomitant use of
      methotrexate. Almost half the patients treated with infliximab achieved an ACR 50
      [RR 49.00 (95% CI 3.06 to 785.06)] and over one-quarter achieved an ACR 70 [RR
      31.00 (95% CI 1.90 to 504.86)] compared with none of the placebo group,
      demonstrating a good level of efficacy. In addition, 75% of patients treated with
      infliximab achieved a PsARC [RR 3.55 (95% CI 2.05 to 6.13)]. The beneficial
      treatment effect on psoriasis was also statistically significant with a mean
      difference in percentage change from baseline in PASI of -5 (95% CI -6.8 to 
      3.3), as was the percentage improvement from baseline in HAQ score with
      infliximab compared with placebo [mean difference 51.4 (95% CI 48.08 to 54.72)],
      indicating a beneficial effect of infliximab on functional status. Uncontrolled
      data from all measures of joint disease, psoriasis and HAQ collected up to 50
      weeks of follow-up reflect those at 16 weeks. There were no radiographic
      assessments, so nothing can be determined about the potential or otherwise of
      infliximab to delay the progression of joint disease. Using the York cost
      effectiveness model, infliximab was consistently dominated by etanercept because
      of its higher acquisition and administration costs without superior
      effectiveness. The incremental cost per quality-adjusted life-year (QALY) gained
      of etanercept compared with palliative care ranged from 14,818 pounds (females,
      40-year time horizon) to 49,374 pounds (males, 1-year time horizon) if it is
      assumed that, when patients eventually fail on biological therapy, their
      disability (in terms of HAQ score) deteriorates by the same amount as it improved
      when they initially respond to treatment (rebound equal to gain). Results for
      etanercept ranged from 25,443 pounds (females, 40-year time horizon) to 49,441
      pounds (males, 1-year time horizon) per QALY gained under the assumption that,
      when patients fail on therapy, their disability level returns to what it would
      have been had they never responded (rebound equal to natural history).
      CONCLUSIONS: The limited data available indicated that etanercept and infliximab
      are efficacious in the treatment of PsA with beneficial effects on both joint and
      psoriasis symptoms and on functional status. Short-term data indicated that
      etanercept can delay joint disease progression, but long-term data are needed.
      There are no controlled data as yet to indicate that infliximab can delay joint
      disease progression. Treatment with both etanercept and infliximab for 12 weeks
      demonstrated a significant degree of efficacy, with no statistically significant
      difference between them. For both drugs, adverse events were common with mild
      injection/infusion reactions being the main treatment-related effect. The York
      model indicated that etanercept is more cost-effective than infliximab as it has
      a lower cost with little difference in outcomes. The cost-effectiveness of
      etanercept is also sensitive to assumptions made about the extent of disease
      progression when patients are responding to therapy. The number of years for
      which a patient can be safely on biologicals is uncertain so these results should
      be considered with caution. Further research should include long-term controlled
      trials to confirm benefits, review adverse events and to explore further the
      implications of biologic therapy.

PMID- 16948891
TI  - The cost-effectiveness of testing for hepatitis C in former injecting drug users.
AB  - OBJECTIVES: To evaluate the effectiveness and cost-effectiveness of testing for
      hepatitis C (HCV) among former injecting drug users (IDUs). DATA SOURCES:
      Electronic databases 1996-October 2004. Trent Regional Database Study. Routine UK
      mortality data. REVIEW METHODS: A decision analytic model was developed to
      investigate the impact of case-finding and treatment on progression of HCV
      disease in a hypothetical cohort of 1000 people. This was compared with a cohort
      in whom no systematic case-finding is implemented but spontaneous presentation
      for testing is allowed to occur. A group of epidemiological and clinical experts
      informed the structure of the model, which has three main components: (1) testing
      and diagnosis, (2) treatment, and (3) long-term consequences of infection. A
      fourth component, case-finding strategies, examines the potential impact of case
      finding in three settings: prisons, general practice and drug services. RESULTS:
      Case-finding for HCV is likely to prevent, for 1000 people approached, three
      cases of decompensated cirrhosis, three deaths due to HCV and one case of
      hepatocellular cancer (at 30 years). Twenty-five additional people are likely to
      undergo combination therapy as a result of initial case-finding. One liver
      transplant is likely to be prevented for 10,000 people included in case-finding.
      Case-finding is likely to cost, in the general case, around pounds sterling
      760,000 more than a policy of not case-finding. The total cost of either strategy
      is high and driven predominantly by the cost of treatment with combination
      therapy (the costs of long-term consequences are heavily discounted owing to the
      duration of the model). Systematically offering testing to 1000 people would cost
      around pounds sterling 70,000. In terms of life-years gained, case-finding is
      likely to result in an additional life-year gained for an investment of pounds
      sterling 20,084. Taking impacts on quality of life into account gives an estimate
      for the cost-utility of case-finding as pounds sterling 16,514 per QALY. The
      probabilistic sensitivity analysis shows that, if NHS policy makers view pounds
      sterling 30,000 per QALY as an acceptable return on investment, there is a 74%
      probability that case-finding for HCV would be considered cost-effective. At
      pounds sterling 20,000 per QALY, the probability that case-finding would be
      considered cost-effective is 64%. In all analyses, the probability of case
      finding being considered cost-effective at a level of pounds sterling 30,000 per
      QALY was high. Case-finding in drug services is likely to be the most expensive,
      owing to the high prevalence of cases in the tested population. Correspondingly,
      benefits are highest for this strategy and cost-effectiveness is similar, in
      average terms, to the general case. Case-finding in general practice by offering
      testing to the whole population aged 30-54 years is, paradoxically, estimated to
      be the least expensive option as only a small number of people accept the offer
      of testing and HCV prevalence in this group is much higher than would be expected
      from the general population. Two approaches to case-finding in prison were
      considered, based on the results of studies in Dartmoor and the Isle of Wight
      prisons. These differed substantially in the prevalence of cases identified in
      the tested populations. The analysis based on data from Dartmoor prison had the
      least favourable average cost-effectiveness of the strategies considered (pounds
      sterling 20,000 per QALY). Subgroup analyses based on duration of infection show
      that case-finding is likely to be most cost-effective in people whose infection
      is more long-standing and who are consequently at greater risk of progression. In
      people who were infected more than 20 years previously, case-finding yields
      benefits at around pounds sterling 15,000 per QALY. Treatment effectiveness was
      modelled using estimates from randomised controlled trials and lower rates of
      viral response may be seen in practice. However, estimates of cost-effectiveness
      remained below pounds sterling 30,000 for all levels of treatment effectiveness
      above 58% of those shown in the relevant trials. The value of information
      analysis, based on assumptions that 10,000 people might be eligible for case
      finding and that programmes would run for 15 years, suggests that the maximum
      value of further research into case-finding is in excess of pounds sterling 19
      million. Partial expected value of perfect information (EVPI) analysis shows that
      the utility estimates used in the model eclipse all other factors in terms of
      importance to parameter uncertainty. This is not surprising, since the point
      estimates for differences in utility between states and across the arms of the
      model are small. CONCLUSIONS: Case-finding for hepatitis C is likely to be
      considered cost-effective by NHS commissioners. Although there remains
      considerable uncertainty, it appears unlikely that cost-effectiveness would
      exceed the levels considered acceptable. Further improvements in the
      effectiveness of treatments to slow or halt disease progression are likely to
      improve the cost-effectiveness of case-finding. Case-finding is likely to be most
      cost-effective if targeted at people whose HCV disease is probably more advanced.
      Further empirical work is required to specify, in practice, different approaches
      to case-finding in appropriate settings and to evaluate their effectiveness and
      cost-effectiveness directly.

PMID- 16948892
TI  - [Fusion expression and affinity purification of a human novel gene tsbp in
      eukaryotic cells].
AB  - AIM: To construct an eukaryotic expressing vector of the human novel gene testis
      sperm binding protein (tsbp), and to express fusion protein and purify the
      recombinant protein by affinity chromatography. METHODS: The novel gene tsbp was
      amplified by PCR from the prokaryotic expressing plasmid pGEX-5X-1/tsbp and an
      eukaryotic expressing vector pcDNA3.1/myc-His(-)B/tsbp was constructed after DNA
      recombination. After transfecting HEK293 cells with this recombinant vector via
      liposome mediation, the expression of the fusion protein was detected by RT-PCR,
      immunofluorescence and Western blot. Fusion protein His6-tsbp was purified from
      the cell lysis by immobilized metal affinity chromatography (IMAC) and the
      efficiency of purification was detected by SDS-PAGE and Western blot. RESULTS:
      DNA sequencing and restriction endonuclease digestion analysis indicated that the
      eukaryotic expression vector pcDNA3.1/myc-His(-)B/tsbp had been constructed
      successfully. After the recombinant plasmid being transfected into HEK293 cells,
      RT-PCR verified the expression of tsbp mRNA. The result of immunofluorescence
      assay was positive and the fusion protein could be detected by Western blot of
      transfected HEK293 cells. The purified fusion protein could also be detected by
      SDS-PAGE and Western blot. CONCLUSION: The novel gene tsbp was successfully
      cloned, expressed and purified in the form of His6 fusion protein, which is
      helpful for further study of the function of this testis sperm binding protein.

PMID- 16948893
TI  - [Up-regulation of IFN-alpha on expression of MICA in the cervical carcinoma cell
      lines].
AB  - AIM: To investigate the effect of IFN-alpha on expression of MHC class I chain
      related protein A (MICA) in the cervical carcinoma cell lines. METHODS: The
      cervical carcinoma cell lines (HeLa and Caski) were treated with IFN-alpha. The
      expression of MICA was measured by RT-PCR and by immunohistochemical staining.
      The cytotoxicity of human NK cells to the IFN-alpha treated cervical carcinoma
      cells was detected by MTT method. RESULTS: The mRNA and protein expression of
      MICA was up-regulated by IFN-alpha in HeLa and Caski cells in a time and dose
      dependent manner. Compared to Caski cells which weakly expressed MICA, higher
      cytolytic activity of NK cells was found against HeLa cells, which expressed
      relatively higher level of MICA. After being treated with IFN-alpha for 3 d, the
      susceptibility of the two cervical carcinoma cells to NK cytolysis was increased
      significantly. CONCLUSION: IFN-alpha can up-regulate the MICA expression in the
      cervical carcinoma cell lines and thereby enhance the susceptibility to cytolysis
      of NK cells.

PMID- 16948894
TI  - [Construction and expression of eukaryotic expression plasmid containing rat TCR
      Vbeta8.2 gene].
AB  - AIM: To construct the recombinant eukaryotic expression vector pTARGET-TCR
      Vbeta8.2 and detect its their expression. METHODS: Gene encoding TCR Vbeta8.2 was
      amplified by RT-PCR from spleen cells of Lewis rats, and then cloned into
      eukaryotic expression vector pTARGET. Recombinant clones were identified by
      blue/white screening on indicator plates after transformed into E.coli strain
      JM109, and then by bacteria colonies PCR and DNA sequencing. Recombinant plasmid
      was injected into BALB/c mice intramuscularly. Then the injected skeletal muscle
      was isolated, and expression of TCR Vbeta8.2 gene was detected by RT-PCR and
      immunohistochemistry. Immunocytochemical staining was used to detect the
      expression of pTARGET-TCR Vbeta8.2 gene after the recombinant plasmid was
      transfected into COS-7 cells by lipofectamine. RESULTS: DNA sequencing
      demonstrated that TCR Vbeta8.2 gene was successfully inserted into pTARGET. RT
      PCR demonstrated that TCR Vbeta;8.2 gene was successfully expressed in the
      injected muscle. Immunohistochemistry staining showed the expression of
      recombinant plasmid in the transfected COS-7 cells. CONCLUSION: The eukaryotic
      expression vector pTARGET-TCR Vbeta8.2 was successfully constructed and expressed
      in vivo and vitro, which would lay foundation for further studies on the
      protective effects of TCR Vbeta DNA vaccine on CIA.

PMID- 16948895
TI  - [Expression and analysis of biological activity of wild-type and mutant
      interleukin-13 in E.coli].
AB  - AIM: To express recombinant wild-type human interleukin-13 (rhIL-13) and mutant
      interleukin-13 (rhIL-13') in E.coli BL21 (DE3) and get active proteins through
      purification and renaturation. METHODS: IL-13 and IL-13' gene fragments were
      amplified by PCR and site-directed mutagenesis PCR, respectively and then were
      inserted into expression vector pET30a(+). Recombinant plasmids were transformed
      to E.coli BL21 (DE3) and were expressed under IPTG induction. Expressed products
      were purified through Ni-NTA chromatographic column. The purified proteins were
      renatured by GSH-GSSG (reduced glutathione, oxidized glutathione) system and
      dialysis and their bioactivity was detected by MTT colorimetry. RESULTS: The
      expressed recombinant proteins existed in the form of inclusion body with
      relative molecular mass about 17 000. The recombinant proteins with higher purity
      were obtained after purification. The renatured inclusion bodies were
      biologically active. CONCLUSION: rhIL-13/rhIL-13' with biological activity have
      been obtained successfully, which lays the foundation for further study on their
      function.

PMID- 16948896
TI  - [Immune response induced by combinant immunization of different HBsAg vaccines in
      mice].
AB  - AIM: To investigate the specific humoral and cellular immune response induced by
      prime-boost immunization of HBsAg protein vaccine (P), recombinant vaccinia virus
      vaccine (V) and DNA vaccine (D) in mice. METHODS: Groups of BALB/c mice were
      primed by one of the three vaccines P, V or D and boosted by another vaccine at
      2, 5, 8 and 11 week later, thus 9 immune combinations were made: PP, PV, PD, VP,
      VV, VD, DP, DV and DD. Serum samples were collected at week 2, 5, 8 and 11 and
      levels of anti-HBsAg IgG antibodies and their sub-isotypes were determined. Seven
      days after every boost, spleen cells of vaccinated mice were separated and the
      specific CTL lysis ratio of P815S cells were determined. RESULTS: Among the three
      HBsAg vaccines P, V and D, V could induce the quickest humoral immune response.
      The memory humoral immune response induced by P was the strongest. D induced the
      weakest antibody titer. The ratio of specific IgG1/IgG2a indicated that antibody
      induced by PP was more polarized to Th2. The other groups induced balanced
      Th1/Th2 immune response. Among all the groups, VD and DV induced the strongest
      CTL response, and the specific lysis ratio of P815S cells was 71% and 64%,
      respectively. CONCLUSION: The experimental results suggested that among all the
      immune combinations, PV, PD, VP and VD can induce better humoral immune response
      while DV and VD can induce stronger CTL response in BALB/c mice.

PMID- 16948897
TI  - [T cell-mediated protective effect in cytomegalovirus infected murine
      astrocytes].
AB  - AIM: To explore T cell-mediated restriction of cytomegalovirus (CMV) in murine
      astrocytes. METHODS: A T cell-astrocyte coculture system was established, in
      which astrocytes were infected with mouse cytomegalovirus. Proliferation of T
      cells was observed under inverted microscope and detected after CFSE staining by
      flow cytometry. ELISA was used to detect the levels of IFN-gamma and TNF-gamma in
      coculture supernatants. Observation of astrocyte cytopathic effect (CPE) and PCR
      assay of cytomegalovirus DNA were also performed. RESULTS: After coculture for 3
      d, T cells proliferation was observed under inverted microscope, and flow
      cytometry assay showed (6.68+/-0.61)% T cells had proliferated (P<0.01 compared
      with uninfected control). The level of IFN-gamma was (22.9+/-3.4) ng/L in
      coculture supernatants (P<0.05 compared with uninfected control). While levels of
      TNF-gamma were under 8 ng/L in both cytomegalovirus infected and uninfected
      groups. After coculture with T cells 31.25%-75% astrocyte CPE was diminished, and
      -75% cytomegalovirus DNA load was reduced. Cell-free coculture supernatants also
      exerted suppressive effect on CPE and viral DNA load. However, the antiviral
      effect of T cells diminished when added to fresh cytomegalovirus infected
      astrocytes, accompanied with the decreased level of T cells proliferation and IFN
      gamma in coculture supernatants, suggesting the inhibition of T cells' function.
      CONCLUSION: Cytomegalovirus infected astrocytes could stimulate T cells
      proliferation and activation. Activated T cells had antiviral effect, which was
      partly mediated by soluble factors. The function of T cells was rapidly inhibited
      after activation, of which the underlying complicated mechanisms remain unclear
      and need further study.

PMID- 16948898
TI  - [Study on relationship between HBV post-transcriptional regulatory element and
      response to IFN-alpha by using a reporter gene luciferase].
AB  - AIM: To identify the function of HBV post-transcriptional regulatory
      element(HPRE) in response to IFN-alpha by using the reporter gene luciferase
      (LUC). METHODS: The gene encoding LUC was obtained by PCR from the vector pGEM
      luc and then cloned into the eukaryotic expression vector pcDNA3.0. The HPRE,
      HPREalphabeta(1) and HPREbeta(1)beta(2) fragments were amplified by PCR from HBV
      genome and then cloned into the recombinant vector pcDNA3.0-luc. These
      constructed plasmids were transfected into the human hepatoma cell line HepG2.
      The expression of LUC before and after the addition of IFN-alpha was detected by
      LUC assay system. RESULTS: The DNA sequencing analysis showed that the
      recombinant plasmids pcDNA3.0-luc, pcDNA3.0-luc-HPRE, pcDNA3.0-luc-HP
      REalphabeta(1) and pcDNA3.0-luc-HPREbeta(1)beta(2) were successfully constructed.
      The results of LUC detection assay showed that HPRE, HPREalphabeta(1) and
      HPREbeta(1)beta(2) could enhance the expression of LUC before the addition of IFN
      alpha. When IFN-alpha was added, only the fragment of HPRE, HPREbeta(1)beta(2)
      could significantly reduce the expression of LUC, but the expression of LUC was
      not influenced by HPREalphabeta(1). CONCLUSION: The functional element beta(2) of
      HPRE plays a more important part in response to IFN-alpha than the element alpha
      and beta(1), which may be valuable for further research on mechanisms of IFN
      alpha therapy in HBV infection and function of HPRE binding protein.

PMID- 16948899
TI  - [Expression of mouse CD1.1 in CHO cells and its stimulatory function on NKT
      cells].
AB  - AIM: To get cell lines which express mouse CD1.1 (mCD1.1) stably and to study the
      stimulatory effects of mCD1.1 on lymphocytes from many tissues. METHODS: The
      intestinal epithelial cells were isolated and their total RNA was prepared. By RT
      PCR, the gene coding mCD1.1 was obtained and then cloned into the pcDNA3.1 vector
      through BamH I and EcoR I. The reconstructed plasmid, named pcDNA3.1-mCD1.1, was
      transfected into CHO cells by electroporation. The clones that grew well in the
      medium containing G418 were selected and their mCD1.1 expression was analyzed by
      RT-PCR and flow cytometry(FCM). The mCD1.1-expressing CHO cells were co-cultured
      with lymphocytes freshly isolated from the liver or mesenteric lymph nodes with
      or without LPS. The CHO cells were treated with mitomycin C to inhibit their
      proliferation. The lymphocyte proliferation was detected by MTT. In addition, the
      lymphocytes collected from the co-culture system were stained with fluorescein
      labeled monoclonal antibodies against mouse NK1.1 and CD3. The double positive
      cells were detected by FCM. RESULTS: By RT-PCR, the gene coding mCD1.1 was
      acquired, identical to that reported by some authors with one base different from
      that reported by Genbank. Many clones that express mCD1.1 stably were obtained.
      MCD1.1-expressing CHO cells could stimulate lymphocytes to proliferate in the
      presence or absence of LPS and elevate the percentage of NK1.1 and CD3 double
      positive cells. CONCLUSION: The mCD1.1 expressed on the membrane of CHO cells
      could stimulate the proliferation of NKT cells.

PMID- 16948900
TI  - [Effect of rapamycin and dexamethasone on differentiation and maturation of
      murine bone marrow-derived dendritic cells].
AB  - AIM: To observe the effect of rapamycin (Rap) and dexamethasone (Dex) on
      differentiation and development of murine bone marrow-derived dendritic cells
      (DC) in vitro. METHODS: DC cells generated from C57BL/6 murine bone marrow cells
      were induced by GM-CSF and IL-4. During the course, Rap or Dex was added to the
      culture and the cells were then stimulated by LPS. (1)Morphology development of
      DCs was observed by inverted microscope and scanning electron microscope.(2)The
      cells were analyzed by flow cytometry (FCM) to determine the proportion of
      CD11c(+) cells and the change of CD86 and MHC class II molecule.(3)The influence
      of DCs treated by Rap or Dex on the allogeneic T cell proliferation was studied
      by one-way MLR. RESULTS: (1)The morphology of DCs maintained in a durable state
      of immaturity after Rap or Dex pretreatment.(2)The expression of CD11c and MHC-II
      slightly decreased but CD86 dramatically reduced on Rap-treated DC cells. There
      was close relationship between the expression of CD11c on Dex-treated cells and
      the dosage of Dex. The surface expression of CD86 and MHC-II dramatically reduced
      on Dex-treated DCs. Moreover, DCs treated by Rap or Dex were both able to resist
      the maturation triggered by LPS.(3)Bone marrow-derived DCs cultured with Dex or
      Rap had a lower stimulatory effect on allogeneic T cells compared with that of
      mature DCs. CONCLUSION: Rap and Dex could keep DCs in durable immaturity.
      Compared with Dex, which inhibited the expression of co-stimulatory molecules,
      Rap hardly influenced the differentiation of DCs and the expression of MHC class
      II molecules.

PMID- 16948902
TI  - [Role of Fas-FasL and caspase-3 signal transduction pathway in promoting
      apoptosis of T lymphocyte subset in SLE patients].
AB  - AIM: To explore the relationship between Fas-FasL-mediated signal transduction
      pathway and apoptosis disorder of T lymphocyte subset in SLE patients. METHODS:
      The expression rate of membrane Fas, FasL and that of intracellular activated
      caspase-3 of T lymphocyte subset were determined by flow cytometry. RESULTS:
      Compared with healthy control group, the expression rate of membrane Fas on
      CD4(+) T cells significantly increased in SLE patients in the active and inactive
      phases (P<0.05), however, that on CD8(+) T cells slightly increased but there was
      no statistical significance (P>0.05). The expression rate of FasL on T cell
      subset in SLE patients in the active and inactive phases significantly increased
      (P<0.05) but there was no obvious difference of the expression rate of Fas and
      FasL on T cell subset between the two disease groups (P>0.05). The expression
      rate of intracellular activated caspase-3 in T cell subset of SLE patients in the
      active phase was notably higher than that in the inactive phase and healthy
      control group (P<0.05). The expression rate of intracellular activated caspase-3
      in T cell subset of SLE patients in the inactive phase was slightly higher than
      that in health control group but there was no statistical significance.
      CONCLUSION: Apoptotic speed of T lymphocyte subset in SLE patients was
      accelerated while CD4(+) T cells were in a state of active apoptosis. It is
      possible that Fas-FasL signal transduction pathway plays an important role in the
      induction of T cell apoptosis. The degree of apoptosis of T lymphocytes closely
      correlates with the disease's activity in SLE patients.

PMID- 16948901
TI  - [Quercetin inhibits growth and induces apoptosis of human gastric carcinoma
      cells].
AB  - AIM: To study the effect of quercetin on the growth and apoptosis of human
      gastric carcinoma cell line MGC-803. METHODS: The measurement of inhibitory rate
      and apoptotic index(AI) of quercetin were done by MTT assay and TUNEL assay. The
      positive expression rate of P53, C-myc and P16 were detected by
      immunocytochemical staining. RESULTS: Quercetin at concentrations ranging from 40
      mumol/L to 100 mumol/L significantly inhibited the proliferation of MGC-803 cells
      in a dose- and time-dependent manner (P<0.01). TUNEL assay indicated that the
      number of apoptotic cells in quercetin-treated group was greater than that in the
      control group (P<0.01). Expression of P53 and C-myc protein decreased following
      quercetin induction in a dose-dependent manner, whereas P16 expression increased
      significantly compared with that of the control group (P<0.01). CONCLUSION:
      Quercetin can inhibit the growth and induce apoptosis of MGC-803 cells in a dose-
      and time-dependent manner. Its mechanisms may be relevant to the down-regulation
      of P53 and C-myc protein expression as well as up-regulation of P16 expression.

PMID- 16948903
TI  - [Relationship between anti-tumor effects of melphalan and IFN-gamma].
AB  - AIM: To investigate the relationship between IFN-gamma and anti-tumor effects of
      melphalan in vivo. METHODS: Different gene-type mice (IFN-gamma(+/+), IFN
      gamma(+/-) and IFN-gamma(-/-)), which had the same genetic background of C57BL/6,
      were used in this experiment. Murine lymphoma EL4 cells were inoculated
      subcutaneously into different gene-type mice simultaneously. Twelve days later,
      7.5 mg/kg melphalan was used intraperitoneally to treat all these IFN-gamma(+/+),
      IFN-gamma(+/-) and IFN-gamma(-/-) tumor-bearing mice. Tumor size was observed and
      recorded every one to three days in these different gene-type mice subsequently.
      RESULTS: After melphalan (7.5 mg/kg) treatment, tumor size decreased at a similar
      rate in IFN-gamma(-/-), IFN-gamma(+/-) and IFN-gamma(+/+) mice within the first 3
      d. Tumors shrank further or completely disappeared in most of IFN-gamma(+/-) and
      IFN-gamma(+/+) mice, whereas tumors grew gradually in all IFN-gamma(-/-) mice.
      CONCLUSION: 7.5 mg/kg melphalan has obvious anti-tumor effects on tumor-bearing
      IFN-gamma(+/+) and IFN-gamma(+/-) mice, but little effects on IFN-gamma(-/-)
      mice. These data suggest that IFN-gamma is required for the anti-tumor effects of
      melphalan on tumor-bearing mice in vivo.

PMID- 16948904
TI  - [Immunogenicity of chimeric gene vaccine Mtb8.4/hIL12].
AB  - AIM: To construct chimeric gene vaccine Mtb8.4/hIL-12, express it in COS-7 cells
      and study its immunogenicity. METHODS: Chimeric gene Mtb8.4/hIL-12 was amplified
      by PCR and cloned into the eukaryotic vector pCI-neo to construct the recombinant
      plasmid pCI-neo-Mtb8.4/hIL12. After the recombinant plasmid was identified by
      restriction enzyme digestion analysis, PCR and DNA sequencing, COS-7 cells were
      transfected with pCI-neo-Mtb8.4/hIL12 through cationic liposome. 48 hours later,
      the expression of mRNA was detected by RT-PCR and the level of hIL-12 in culture
      supernatant and cell lysates were detected by Western blot. C57BL/6N mice were
      vaccinated with chimeric gene vaccine Mtb8.4/hIL-12 three times at the interval
      of 3 weeks each time. Four weeks after the final inoculation, three mice were
      sacrificed to assess the cytotoxicity of CTLs and response to cytokine. RESULTS:
      The recombinant plasmid pCI-neo-Mtb8.4/hIL12 was constructed successfully. After
      COS-7 cells were transfected with pCI-neo-Mtb8.4/hIL12, chimeric gene
      Mtb8.4/hIL12 was expressed in COS-7 cells. The chimeric gene vaccine could induce
      strong antigen-specific immune response. With the increase of IFN-gamma and IL-2
      secretion and the decrease of IL-4 secretion, the cytotoxicity of specific CTLs
      was heightened. CONCLUSION: Recombinant plasmid pCI-neo-Mtb8.4/hIL12 has been
      successfully constructed and expressed in COS-7 cells. The constructed chimeric
      gene vaccine Mtb8.4/hIL12 is of strong immunogenicity and can obviously induce
      the cytotoxicity of CTLs.

PMID- 16948905
TI  - [The expression of SDF-1/CXCR4 in trophoblasts and their role in maternofetal
      immune tolerance].
AB  - AIM: To investigate the expression of SDF-1/CXCR4 in trophoblasts and their role
      in maternofetal immune tolerance. METHODS: Extra-villous trophoblasts were highly
      purified from villi of first trimester. The expression of SDF-1 and CXCR4 in
      villi was detected by immunocytochemical staining. A chorioepithelioma cell line
      from trophoblasts with high expression of CXCR4 was screened by flow cytometry to
      test the chemotaxis of SDF-1 in transwell. The expression of SDF-1 and CXCR4 in
      villi of first trimester and placentas of last trimester was detected by
      immunohistochemical staining. RESULTS: SDF-1 and CXCR4 were expressed in extra
      villous trophoblasts. In a certain coverage, the chemotactic activity of SDF-1
      had positive correlation with its concentration (r=0.68, P<0.01), and the maximum
      CI (chemotactic index) was 1.62+/-0.12. CONCLUSION: SDF-1 and CXCR4 play an
      important role in gestation and they are also important in maternofetal immune
      tolerance during pregnancy.

PMID- 16948906
TI  - [Increased sensitivity to chemotherapeutic drug by RNAi targeting Hsp701A in
      HepG2 cells].
AB  - AIM: To investigate the effects on chemotherapeutic sensitivity to the drugs of
      tumor cells induced by Hsp701A targeting siRNA expression vector. METHODS:
      Specific small interference RNA (siRNA) targeting Hsp701A gene was generated and
      its eukaryotic expression vector was constructed and transfected into human HepG2
      cells.Sensitivity to the chemotherapeutic drug of HepG2 cells transfected with
      the vector was detected by MTT colorimetry. RESULTS: The eukaryotic expression
      vector of siRNA targeting Hsp701A was successfully constructed and transfected
      into human HepG2 cells. Sensitivity to the chemotherapeutic drug of HepG2 cells
      was increased after Hsp701A was knock down (P<0.05). CONCLUSION: Knockdown of
      Hsp701A gene by siRNA enhances sensitivity to chemotherapeutic drug in HepG2
      cells.

PMID- 16948907
TI  - [Study of cytokines secreted by tumor-draining lymph node cells from lung cancer
      patients induced with different stimulators].
AB  - AIM: To investigate the influence of different stimulators on cytokines secretion
      of tumor-draining lymph node (TDLN) cells and study antitumor effects and
      mechanism of TDLN cells. METHODS: IL-12 p70, IFN-gamma, TNF-alpha and NO which
      were secreted by TDLN cells induced by different stimulators (IL-2 group, IL
      2+autologous tumor antigen group, IL-2+GM-CSF+IL-4+autologous tumor antigen group
      and IL-2+GM-CSF+IL-4+LPS group) were detected by ELISA and Griess after TDLN
      cells were stimulated for 7, 14 and 21 d. RESULTS: The rate of CD83(+) cells of
      TDLN cells induced by IL-2+GM-CSF+IL-4+autologous tumor antigen and IL-2+GM
      CSF+IL-4+LPS was significantly increased. The TDLN cells in the two groups
      secreted much more IL-12 p70, IFN-gamma and TNF-alpha than IL-2 group and IL
      2+autologous tumor antigen group. The TDLN cells stimulated by IL-2+GM-CSF+IL
      4+LPS secreted significantly more NO than the other three groups. TDLN cells in
      each group secreted IL-12 p70, IFN-gamma and NO at the highest level after TDLN
      cells were stimulated for 14 d. CONCLUSION: Different stimulators can make TDLN
      cells produce different number of CD83(+) cells (DC), which gives TDLN cells
      different antitumor activity.

PMID- 16948908
TI  - [Construction of hepatoma-targeting recombinant co-expression adenovirus vector
      of SEA and CD80 and identification of its expression].
AB  - AIM: To construct hepatoma-targeting recombinant co-expression adenovirus vector
      of Staphylococcal enterotoxin A (SEA) and CD80 gene. METHODS: Us-ing the
      adenovirus transfer plasmids pShuttle and pShuttle-CMV, we constructed a new
      transfer plasmid pShuttle2 with polyA signal sequence instead of CMV
      enhancer/promoter. AFP enhancer, promoter, SEA or CD80 gene was subcloned into
      pShuttle2 from the vectors pKS-EP or pMD18-T-BIS respectively, and then the
      constructed plasmid pShuttle2-BIS containing AFP enhancer, promoter, SEA or CD80
      gene was cotransformed into E.coli BJ5183 with backbone vector pAdEasy-1 to
      obtain recombinant adenovirus DNA. The recombinant adenovirus DNA was transfected
      into 293 cells to prepare adenovirus. After AFP-producing cell line Hepa1-6 and
      AFP-nonproducing cell lines B16 and NIH3T3 were infected by recombinant
      adenovirus, the expression of SEA and CD80 on the surface of cells was detected
      by indirect immunofluorescent staining, laser confocal microscope and flow
      cytometry (FCM). RESULTS: SEA and CD80 was specifically co-expressed on the
      surface of infected Hepa1-6 cells but not on B16 and NIH3T3 cells. CONCLUSION:
      Hepatoma-targeting recombinant co-expression adenovirus vector of SEA and CD80
      gene was successfully constructed, which lays the foundation for further research
      on application of SEA and CD80 in targeted gene therapy for hepatoma and the
      underlying immunological mechanisms.

PMID- 16948909
TI  - [Influence of bifidobacterial whole peptidoglycan on cellular immune response
      induced by recombinant HBsAg].
AB  - AIM: To explore the effect of bifidobacterial whole peptidoglycan (BWPG) on
      cellular immune response to recombinant hepatitis B surface antigen (rHBsAg).
      METHODS: BWPG was used as an adjuvant of rHBsAg to immunize BALB/c mice. The
      growth state and development of central lymphoid organ of immunized mice were
      observed. Then the killing activities of NK cells and CTLs, the proliferation and
      cytokine production of splenic lymphocytes were examined. RESULTS: After
      immunization with BWPG, no visible side effect was observed in immunized mice.
      The thymus and spleen tissues assumed hyperplasia appearance. The killing
      activities of NK cells and CTLs in spleen were enhanced. The proliferation of
      splenic lymphocytes was active and cytokine production was increased. CONCLUSION:
      BWPG can promote hyperplasia of central lymphoid organ and enhance the cellular
      immune response to rHBsAg.

PMID- 16948910
TI  - [Expression map of immune-related genes on PBMCs in familial clustering patients
      with chronic virus hepatitis B].
AB  - AIM: To investigate peripheral blood mononuclear cells (PBMCs) immune-related
      gene expression profile in patients with chronic virus hepatitis B(CHB) by
      oligonucleotide gene array technique. METHODS: PBMCs were collected from the
      members of a family of clustering hepatitis B virus (HBV) infection including 5
      CHB patients and 4 healthy spouses and RNA prepared from PBMCs was hybridized to
      high-density oligonucleotide arrays(HG-U133A 2.0 Human Gene Chips, Affymetrix),
      covering the expression of 22 000 human ESTs. Primary scanned image was analyzed
      with DNT software package. RESULTS: Out of the 22 000 ESTs, 24 different immune
      related genes were identified. Among the 24 genes, 7 genes showed increased
      expression and 17 genes showed decreased expression in CHB compared with those in
      healthy spouses. The up-regulated genes were mainly associated with adaptive
      immunity, while the down-regulated genes were associated with innate immunity.
      CONCLUSION: Our findings suggest that HBV infection alters a broad range of
      immunity genes expression and innate immunity-associated genes are important in
      the defense against HBV chronic infection.

PMID- 16948911
TI  - [Differential expression of immune-associated genes in two subcloned cell lines
      from a same human bladder cancer].
AB  - AIM: To screen and identify differentially expressed genes in subcloned lines
      from a same human bladder transitional cell carcinoma (TCC). METHODS: Two bladder
      TCC cell lines (BLX and BLS-211) with different phenotypes but same origin were
      used to screen for differentially expressed genes by suppression subtractive
      hybridization (SSH). RESULTS: 9 over-expressed genes in BLX and 15 in BLS-211
      cells were obtained, respectively. Some Bacillus Galmette-Guerin(BCG)- associated
      genes, such as BCG induced integral membrane protein(BIGM103), fibronectin(FN),
      complement factor B(BF), were over-expressed in BLX cells. And 8 new
      ESTs(Expressed Sequence Tag) in BLS-211 cells were collected by GenBank dbEST
      database with the accession number of DY505708-13, DY230447-8. CONCLUSION: SSH is
      a powerful method for the identification of differentially expressed genes in
      different cell lines or clones. Some BCG-associated genes, which are
      differentially expressed in different cells may contribute to the different
      response to clinical BCG therapy. The identified new ESTs can be cloned for full
      length to further study their functions.

PMID- 16948912
TI  - [Measurement of IL-12 and IL-18 in sera of patients with autoimmune thyroid
      disease].
AB  - AIM: To provide some evidence for the imbalance of Th1/Th2 cells in patients with
      autoimmune thyroid disease(AITD). METHODS: Concentrations of IL-12 and IL-18 in
      the serum samples of 27 patients with Graves' disease(GD), 24 patients with
      euthyroid Hashimoto's thyroiditis(HT), 25 patients with hypothyroid HT and 20
      normal controls were investigated by ELISA. The activity of thyroid-stimulating
      antibody(TSAb) was also assayed in GD patients. RESULTS: The mean levels of IL-12
      and IL-18 in patients with GD and euthyroid HT were significantly higher than
      those in normal controls. Significant positive correlations were found between
      the level of IL-12 and IL-18 in the two groups. In addition, striking positive
      correlations were noted between the levels of IL-12, IL-18 and the activity of
      TSAb in GD, as well as between the levels of IL-12, IL-18 and the titers of anti
      thyroglobulin antibody(TgAb) in euthyroid HT. However, no differences were
      observed in IL-12 and IL-18 levels between hypothyroid HT and normal controls.
      CONCLUSION: Th1-type cell and related cytokines might play an important role in
      the pathogenesis of HT and GD. Such therapies can aggravate the process of
      disease in GD by suppressing Th2 response and modulating imbalance toward Th1
      predominance.

PMID- 16948913
TI  - [Preparation and identification of rabbit antibody against LRR of Nogo-66
      receptor (NgR)].
AB  - AIM: To prepare rabbit antibody against LRR of Nogo-66 receptor (NgR) and
      identify its properties. METHODS: LRR protein was expressed in E.coli BL21.
      Rabbits were immunized with purified LRR protein to prepare anti-LRR antibody.
      The titer and specificity of prepared antibodies were identified by Western blot
      and immunohistochemical staining, respectively. RESULTS: Purified rabbit anti-rat
      LRR antibody with high titer was obtained. The anti-LRR Ab showed good
      specificity and could be used to detect the NgR in rat brain and spinal cord
      tissues. Immunohistochemical staining indicated that NgR was expressed widely in
      spinal cord neurons. CONCLUSION: Successful preparation of anti-rat LRR antibody
      provides a useful tool for identification and further functional study of NgR
      molecule.

PMID- 16948914
TI  - [Preparation and characterization of the monoclonal antibody against human sperm
      protein 17].
AB  - AIM: To prepare and characterize the monoclonal antibody (mAb) against sperm
      protein 17 (Sp17). METHODS: Human Sp17 cDNA was cloned and recombinant Sp17
      protein was expressed as a fusion protein with an N-terminal 6-His tag. The
      purified recombinant Sp17 protein was used to immunize BALB/c mice for preparing
      mAb. mAb-produced hybridoma cells were screened by ELISA and the specificity of
      mAb was analyzed by immunohistochemical staining and blocking test. RESULTS: Two
      hybridoma cells (3C12 and 3D6) secreting mAb against Sp17 were developed. The
      isotypes of these two mAbs, 3C12 and 3D6, were IgG(1) and IgM, respectively.
      ELISA detection showed that titers of mAbs, 3C12 and 3D6, were 1:64, 1:32 in
      cultured supernatant and 1:1 x 10(5), 1:5 x 10(4) in ascites, respectively. The
      results of immunohistochemical staining and blocking test indicated that 2 mAb
      specifically bound to Sp17 in human and rat testis and human ejaculated
      spermatozoa. Anti-Sp17 mAb also detected Sp17 in ovarian cancer. CONCLUSION: The
      successful preparation of anti-Sp17 mAb will be useful for assessing the native
      distribution and aberrant expression of Sp17 protein.

PMID- 16948915
TI  - [Effect of anti-human DR5 monoclonal antibody on the apoptosis of human
      hepatocyte HL7702 cell lines].
AB  - AIM: To evaluate the effect of a novel anti-human DR5 monoclonal antibody (mAb
      mDRA-6) on the apoptosis of human hepatocyte HL7702 cell lines. METHODS: DR5
      expression on HL7702 cell surface was determined by flow cytometry(FCM). The
      effect of mAb mDRA-6 on the morphous of HL7702 cells was observed by fluorescence
      microscope. mDRA-6 cytotoxicity on HL7702 cells was detected by using MTT
      analysis. The rate of apoptosis was detected by FCM with Annexin V-FITC/PI
      staining. RESULTS: HL7702 cells treated with mDRA-6 exhibited some typical
      apoptotic features in morphology. MTT analysis showed the death rate of HL7702
      cells was 39% in the presence of 40 mg/L mDRA-6 for 6 hours. FCM detection
      indicated the apoptosis rate of the cells was 25.5% in the presence of 3 mg/L
      mDRA-6 for 6 hours with Annexin V-FITC/PI staining. CONCLUSION: mDRA-6 can induce
      the apoptosis of HL7702 cells.

PMID- 16948916
TI  - [Preparation and partial characterization of monoclonal antibodies specific for
      nuclear protein of avian influenza virus].
AB  - AIM: To prepare the monoclonal antibodies (mAbs) specific for nuclear protein
      (NP) of avian influenza virus (AIV) and identify their biological properties.
      METHODS: BALB/c mice were immunized with AIV (formaldehyde-inactivated AIV H9N2,
      Triton X-100-lysed H9N2 and AIV NP expressed in E.coli, respectively). Hybridoma
      cell lines secreting anti-AIV NP mAbs were developed through cell fusion,
      screening and cloning. The mAb's titer was determined by indirect ELISA.
      Specificity of mAbs was identified by cross-reaction test and indirect immuno
      fluorescence assay (IFA). RESULTS: 6 hybridoma cell lines secreting anti-AIV NP
      mAbs were obtained, designated 4F4, 1C3, 1G11, 1C2, 1D10 and 2F7. ELISA detection
      showed that the titers of two mAbs (1G11 and 1D10) out of 6 mAbs were the highest
      (2(-13) and 2(-14), respectively) and their specificity was also better than that
      of the others, confirmed by cross-reaction test and IFA. CONCLUSION: In this
      study 6 mAbs against AIV NP were obtained. The mAbs 1G11 and 1D10 perform the
      best in titer and specificity. This work paves the way for AIV study and
      development of method for rapid detection of AIV.

PMID- 16948917
TI  - [Replacement of the constant region gene of a novel anti-CEA antibody and
      characterization of its biological activity].
AB  - AIM: To convert the subclass of a novel anti-CEA antibody, C2-45, from IgG4 to
      IgG1, and to increase its biological activity. METHODS: V(H) and V(kappa); genes
      were cloned from C2-45(IgG4), then inserted to pAc-kappa-CH3 expression vector
      which contained the constant region gene of human IgG1. The recombinant gene was
      transfected to Sf9 insect cells to produce recombinant virus with high titer and
      obtain recombinant protein. The recombinant protein, in the culture supernatant,
      designated C2-45 (IgG1), was purified by affinity chromatography, and
      characterized for the CEA binding specificity and the biological activity of CDC
      and ADCC. RESULTS: The C2-45 (IgG1), retained the original antigen-binding
      activity and effectively introduced a specific cytotoxicity of complement and
      lymphokine-activated killer cells to the CEA-expressing tumor cells. CONCLUSION:
      The constant region of anti-CEA antibody C2-45 was successfully converted from
      IgG4 to IgG1, which may be useful for immunotherapy of human CEA-expressing
      tumors.

PMID- 16948918
TI  - [Preparation and characterization of anti-Drosophila Dnop5 antibody].
AB  - AIM: To prepare the rabbit antibody against Dnop5 and identify its specificity.
      METHODS: Dnop5 cDNA was amplified by RT-PCR, and then was subcloned into the
      fusion expression vectors pET28a(+). After being expressed in E.coli BL21, the
      truncated Dnop5 protein was purified and used to immunize rabbit. Purified
      antibody was obtained through affinity chromatography column with the expressed
      Dnop5. The specificity of the purified antibody was characterized by Western blot
      and immunohistochemical staining. RESULTS: The Dnop5 gene was successfully
      inserted into pET28a(+). After induction, the fusion protein was expressed in the
      form of inclusion body. The purified fusion protein was obtained by affinity
      chromatography. After immunization of rabbits, the antibody against Dnop5 was
      obtained. Western blot analysis and immunohistochemical staining showed that the
      antibody had a good specificity. CONCLUSION: The rabbit antibody against Dnop5
      has been successfully prepared, which lays the foundation for further study on
      the Dnop5 function.

PMID- 16948919
TI  - [Screening and identification of antibodies against transferrin receptor].
AB  - AIM: To screen the antibodies against transferrin receptor(TfR) from a full
      humanized phage antibody library. METHODS: Total RNA was extracted from HeLa
      cells and then the extracellular domain of TfR gene was amplified by RT-PCR in
      two parts. A full-length gene of extracellular domain was obtained by two rounds
      of PCR. The gene was inserted into the plasmid pPROEX(TM) HTa and transformed
      into E.coli BL21(DE3). Transformant was expressed under 1 mmol/L IPTG induction.
      The target protein was purified and refolded by one-step affinity chromatography
      with Ni(+)-NTA agarose. The antibodies against TfR were screened by proteins
      coupled to immunotubes from a whole-hog humanized phage single chain antibody
      library with sink size of 10(13) cfu/L. RESULTS: The extracellular domain of TfR
      gene with about 1.9 kb was obtained. DNA sequencing of TfR gene proved to be
      identical to the published sequence. Eight single chain antibodies specifically
      binding to human TfR have been screened. CONCLUSION: Antibodies specifically
      binding to natural TfR can be obtained by screening the library with refolded
      protein, which lays the foundation for treatment of tumor and central nervous
      system diseases.

PMID- 16948920
TI  - [Preparation and subcellular localization of antibody against RIP3].
AB  - AIM: To determine the localization of RIP3 in NIH3T3 cell line and explore its
      roles in the signal transduction pathway of TNF-alpha-induced caspase-independent
      cell death. METHODS: RIP3 gene was cloned from NIH3T3 cell line by RT-PCR and the
      amino acid 287-486 sequence of RIP3 was overexpressed in E.coli strain BL21. The
      protein was purified by electrodialysis to immune rabbits. Nine weeks later, the
      serum of the rabbits was harvested and anti-RIP3 polyclonal antibodies was
      purified and its specificity was detected by Western blot. Immunofluorescence was
      used to determine the subcellular localization of RIP3 in NIH3T3 cell line and
      the effects of TNF-alpha and z-VAD.fmk on RIP3 for its localization changing.
      RESULTS: A high concentration of rabbit polyclonal antibody against RIP3 with
      good immunological characteristics was obtained. RIP3 was successfully detected
      by Western blot with anti-RIP3 antibody in 293T cells transfected with pcDNA3
      flag-RIP3 and in mouse NIH3T3 cell line. The results of immunofluorescent
      staining displayed that RIP3 localized in cytoplasm in untreated NIH3T3 cells.
      Treatment with TNF-alpha or z-VAD. fmk alone didn't change its distribution.
      However in the cells induced by z-VAD.fmk and TNF-alpha, RIP3 was detected in
      both cytoplasm and nucleolus. CONCLUSION: The polyclonal antibody against RIP3
      with high concentration and specificity was successfully obtained. In NIH3T3 cell
      line, RIP3 localized in cytoplasm, which was subject to change induced by z
      VAD.fmk and TNF-alpha, suggesting that RIP3 plays an important role in TNF-alpha
      induced caspase-independent cell death signal transduction pathway.

PMID- 16948921
TI  - [Preliminary study on the conditions of solid-phase screening phage antibody
      library].
AB  - AIM: To explore the conditions of solid-phase screening phage antibody library
      and to provide the experimental basis for the design of screening project.
      METHODS: Diverse antibodies including HEV NE2-specific and non-specific humanized
      phage antibodies were used to study the screening conditions, such as the binding
      time of phage antibodies to antigen, the concentration of coating antigen, the
      washing times and elution method. RESULTS: The best binding time of positive
      phage antibody to antigen was 1 min. The highest positive rate of screening was
      obtained under the conditions of washing for 20 to 30 times and pH value of the
      washing solution being 5. The concentration of the coating antigen had no obvious
      influence on the positive rate of screening. Higher positive rate was obtained by
      using 10 mg/L antigen to competitively elute for 1 h. CONCLUSION: Solid-phase
      screening of the phage antibody library is a very complex process, in which there
      are close relationship between the conditions, therefore, appropriate
      readjustment should be made for screening conditions according to concrete
      conditions.

PMID- 16948922
TI  - [Establishment of chemiluminescence immunoassay for detecting Staphylococcal
      enterotoxin B and C1].
AB  - AIM: To establish chemiluminescence immunoassay (CLIA) for detecting
      staphylococcal enterotoxin B (SEB) and C1 (SEC1) and compare its sensitivity and
      stability with ELISA. METHODS: The anti-SEB and SEC1 monoclonal antibodies (mAb)
      were purified by Q Sepharose Fast Flow chromatographic column. The alkaline
      phosphatase (AP) conjugated mAbs FMMU-SEB.D6 and FMMU-SEC1.C4 were used as
      detecting antibodies and the FMMU-SEB.B4 and FMMU-SEC1.G8 mAbs were used as
      coating antibodies in both methods. Phenolphthalein monophosphate (PMP) and
      lumigen APS-5 were employed as substrates for AP in ELISA and CLIA, respectively.
      The light was detected and measured by the GENios analyzer (TECAN Group Ltd.).
      The sensitivities and detect ranges of CLIA and ELISA methods were compared.
      RESULTS: Compared with ELISA, CLIA was more sensitive (0.1 ng/mL vs 0.39 ng/mL)
      and timesaving. Furthermore, the liner range of CLIA was broader than that of
      ELISA (0.78-50 ng/mL vs 3.125-50 ng/mL). CONCLUSION: CLIA for detecting SEB and
      SEC1 are established successfully which may be useful in food monitoring,
      epidemiology survey and detecting SE contaminated samples in environment.

PMID- 16948923
TI  - Pediatric Epstein-Barr Virus-Associated Encephalitis: 10-Year Review.
AB  - Many neurologic manifestations of Epstein-Barr virus (EBV) infection have been
      documented, including encephalitis, aseptic meningitis, transverse myelitis, and
      Guillain-Barr?yndrome. These manifestations can occur alone or coincidentally
      with the clinical picture of infectious mononucleosis. Since 1994, The Hospital
      for Sick Children has maintained a prospective registry of all children admitted
      with acute encephalitis. This report summarizes all cases of Epstein-Barr virus
      associated encephalitis compiled from 1994 to 2003. Twenty-one (6%) of 216
      children, median age 13 years (range 3-17 years), in the Encephalitis Registry
      were identified as having evidence of Epstein-Barr virus infection. This evidence
      consisted of convincing Epstein-Barr virus serology and/or positive cerebrospinal
      fluid polymerase chain reaction (PCR). One patient had symptoms of classic
      infectious mononucleosis; all others had a nonspecific prodrome, including fever
      (n = 17; 81%) and headache (n = 14; 66%). Slightly less than half (n = 10; 48%)
      had seizures and often had electroencephalograms showing a slow background (n =
      12; 57%). Many demonstrated cerebrospinal fluid pleocytosis (n = 17; 81%), and
      71% (n = 15) had abnormal magnetic resonance imaging findings. Two patients died,
      2 suffered mild deficits, and 16 were neurologically normal at follow-up. Most
      patients with Epstein-Barr virus encephalitis do not show typical symptoms of
      infectious mononucleosis. Establishing a diagnosis of Epstein-Barr virus
      encephalitis can be difficult, and, consequently, a combination of serologic and
      molecular techniques should be used when investigating a child with acute
      encephalitis. Most children make full recoveries, but residual neurologic
      sequelae and even death can and do occur. (J Child Neurol 2006;21:384-391; DOI
      10.2310/7010.2006.00114).

PMID- 16948924
TI  - Differentiating Autistic Children With Quantitative Encephalography: A 3-Month
      Longitudinal Study.
AB  - The present study used a single-channel quantitative electroencephalographic
      (EEG) assessment to differentiate autistic children from normal control subjects.
      One hundred five normal and 17 autistic children participated in the study. In
      addition to amplitude measures of the frequency bands of delta, theta, alpha,
      sensorimotor rhythm, and beta and the theta to beta ratio, intra- (6 minutes) and
      intersessional (3 months) consistencies were also examined. The results indicated
      that autistic children showed significantly higher quantitative EEG amplitudes in
      many of the frequency bands than normal children; furthermore, their quantitative
      EEG activities were found to be relatively unstable within a 6-minute session
      compared with normal children. Discriminant function analyses revealed that
      absolute sensorimotor rhythm and beta amplitudes were the best predictors that
      correctly differentiated autistic children from normal children in the present
      sample, with a high accuracy rate of 95.2%. In addition, quantitative EEG
      measurements of normal and autistic children were found to be generally
      consistent across the 3-month period. (J Child Neurol 2006;21:391-399; DOI
      10.2310/7010.2006.00094).

PMID- 16948925
TI  - Ketamine increases opening cerebrospinal pressure in children undergoing lumbar
      puncture.
AB  - Intravenous ketamine, often administered concomitantly with midazolam, is one of
      the most commonly used drugs for procedural sedation in children. Although it is
      considered safe for use in children, ketamine can increase intracranial pressure.
      Hence, this study was carried out to determine whether adding ketamine to
      midazolam prior to performing lumbar puncture would be associated with a higher
      cerebrospinal fluid opening pressure in children with suspected aseptic
      meningitis. Thirty-nine children aged 6 months to 14 years were included: 26 in
      group A (intravenous midazolam plus ketamine) and 13 in group B (intravenous
      midazolam only). Mean cerebrospinal fluid opening pressure in group A was 24.4 cm
      H2O (median 23 cm H2O) compared with 20 cm H2O (median 19.8 cm H2O) in group B (P
      = .011). Intravenous ketamine prior to performing lumbar puncture is associated
      with a significantly higher lumbar cerebrospinal fluid opening pressure in
      children with aseptic meningitis. However, no outcome differences have been found
      between the two groups.

PMID- 16948926
TI  - High levels of Alzheimer beta-amyloid precursor protein (APP) in children with
      severely autistic behavior and aggression.
AB  - Autism is characterized by restricted, repetitive behaviors and impairment in
      socialization and communication. Although no neuropathologic substrate underlying
      autism has been found, the findings of brain overgrowth via neuroimaging studies
      and increased levels of brain-derived neurotrophic factor (BDNF) in
      neuropathologic and blood studies favor an anabolic state. We examined
      acetylcholinesterase, plasma neuronal proteins, secreted beta-amyloid precursor
      protein (APP), and amyloid-beta 40 and amyloid-beta 42 peptides in children with
      and without autism. Children with severe autism and aggression expressed secreted
      beta-amyloid precursor protein at two or more times the levels of children
      without autism and up to four times more than children with mild autism. There
      was a trend for children with autism to show higher levels of secreted beta
      amyloid precursor protein and nonamyloidogenic secreted beta-amyloid precursor
      protein and lower levels of amyloid-beta 40 compared with controls. This favors
      an increased alpha-secretase pathway in autism (anabolic), opposite to what is
      seen in Alzheimer disease. Additionally, a complex relationship between age,
      acetylcholinesterase, and plasma neuronal markers was found.

PMID- 16948927
TI  - Risperidone in children with autism: randomized, placebo-controlled, double-blind
      study.
AB  - Some open-label studies suggest that risperidone can be useful in the treatment
      of certain target symptoms in children with autism. We aimed to study whether the
      use of risperidone in comparison with placebo improved functioning in children
      with autism with regard to behavior (aggressiveness, hyperactivity,
      irritability), social and emotional responsiveness, and communication skills. We
      conducted a randomized, double-blind, placebo-controlled trial with 40
      consecutive children with autism, whose ages ranged from 2 to 9 years, who were
      receiving either risperidone or placebo given orally at a dose of 1 mg/day for 6
      months. Autism symptoms were monitored periodically. The outcome variables were
      total scores on the Childhood Autism Rating Scale (CARS) and the Children's
      Global Assessment Scale (CGAS) after 6 months. Of the 40 children enrolled, 39
      completed the trial over a period of 18 months; 19 received risperidone, and 20
      received placebo. In the risperidone group, 12 of 19 children showed improvement
      in the total Childhood Autism Rating Scale score and 17 of 19 children in the
      Children's Global Assessment Scale score compared with 0 of 20 children for the
      Childhood Autism Rating Scale score and 2 of 20 children for the Children's
      Global Assessment Scale score in the placebo group (P < .001 and P = .035,
      respectively). Risperidone also improved social responsiveness and nonverbal
      communication and reduced the symptoms of hyperactivity and aggression.
      Risperidone was associated with increased appetite and a mild weight gain, mild
      sedation in 20%, and transient dyskinesias in three children. Risperidone
      improved global functioning and social responsiveness while reducing
      hyperactivity and aggression in children with autism and was well tolerated.

PMID- 16948928
TI  - Pilot study of positron emission tomography (PET) brain glucose metabolism to
      assess the efficacy of tongue and body acupuncture in cerebral palsy.
AB  - We aimed to assess the efficacy of tongue and body acupuncture with clinical
      function and brain glucose metabolism in children with a severe type of cerebral
      palsy. Four children were recruited. The motor function belonged to grade 5 of
      the Gross Motor Function Measure (i.e., completely nonambulatory). Daily tongue
      and body acupuncture was applied for 5 days a week for 8 weeks. The Functional
      Independence Scale for Children (WeeFIM), Clinical Global Impression Scale
      (CGIS), and positron emission tomography of the brain with
      [18F]fluorodeoxyglucose (FDG) were performed at baseline and after acupuncture.
      None of the children had any significant change in the Functional Independence
      Scale for Children score, despite the fact that all mothers scored 3 on the
      Clinical Global Impression Scale (i.e., 25% in improvement) in overall function.
      The brain glucose metabolism, however, showed a >10% increase in the frontal,
      parietal, temporal, and occipital cortices and cerebellum. Thus, a short course
      of tongue and body acupuncture was shown to increase brain glucose metabolism,
      despite lacking any clinical functional improvement seen during the eight-week
      course, possibly owing to the severity of the motor dysfunction and the short
      duration of treatment. The objective increase in brain glucose metabolism might
      serve as a surrogate marker for assessing the subclinical efficacy of an
      alternative treatment before any objective clinical improvement is evident. A
      larger-scale study for different degrees of severity of cerebral palsy and an
      impairment model should be undertaken to correlate clinical with neurometabolic
      change.

PMID- 16948929
TI  - Pilot study of efficacy of tongue and body acupuncture in children with visual
      impairment.
AB  - We studied the efficacy of tongue and body acupuncture in affecting visual
      recovery in children with central and peripheral visual disorders. Twelve
      children (five boys, seven girls) (age range 18 months to 14.5 years) with visual
      disorder with static functional visual ability for at least 12 months were
      recruited for the study. The causes of cortical visual impairment (10) included
      severe perinatal asphyxia (4), postencephalitis (1), traumatic brain injury (1),
      hydrocephalus (1), and increased intracranial pressure (3). Peripheral causes (2)
      were due to congenital optic atrophy. We used the following assessment tools:
      clinical visual improvement, defined as improvement of vision by one grade in one
      or both eyes with measurement of visual acuity; the functional visual outcome
      scale of 0 to 5, with positive outcome defined as improvement in one level on a
      functional scale; visual evoked potential, with positive improvement defined as
      10% improvement in P100 latency of one or both eyes; [18F]-fluorodeoxyglucose
      (FDG) positron emission tomography (PET) of the brain, with positive improvement
      defined as a 10% increase in glucose metabolism in one or both occipital lobes;
      and the Clinical Global Impression Scale (parental report). Tongue and body
      acupuncture consisted of 60 sessions, with 5 sessions per week. Four children
      showed clinical or functional improvement (33%). Of nine children with abnormal
      visual evoked potentials, five had improvement (56%). Of seven children who
      underwent PET, six had improvement in glucose metabolism in the visual cortex
      (86%). Seven parents (58%) reported improvement (three children had 75%
      improvement; four children had 25% improvement). There was a significant
      correlation between the interval of onset of visual impairment and starting
      treatment with clinical or functional outcome, with a longer interval resulting
      in a better outcome (P = .0282). However, there was no correlation between cause,
      severity, or clinical or functional visual outcome with improvement in the visual
      evoked potential or PET. We demonstrated that tongue and body acupuncture can
      improve the visual status of children with visual disorders, both peripheral and
      central in origin. As children with chronic visual impairment also showed some
      visual recovery, more studies should be done to assess the full potential of
      acupuncture as an adjunct to Western medicine in neuroplasticity.

PMID- 16948930
TI  - Neurodevelopmental outcome of severe neonatal hemolytic hyperbilirubinemia.
AB  - We recruited 128 neonates with hyperbilirubinemia over a 5-year period (1995
      2000) to study the short- and long-term effects of hemolytic hyperbilirubinemia
      on the auditory brainstem pathway and neurodevelopmental status. These children
      were divided into two groups: (1) a hemolytic group (n = 29; ABO incompatibility
      [n = 19], Rh incompatibility [n = 1], glucose-6-phosphate dehydrogenase
      deficiency [n = 8] and both ABO incompatibility and glucose-6-phosphate
      dehydrogenase deficiency [n = 1]) and (2) a nonhemolytic group (n = 99). All
      received phototherapy. Exchange transfusions were performed for four (13.8%) in
      the hemolytic group and three (3%) in the nonhemolytic group. The brainstem
      auditory evoked potential was recorded at a mean age of 3.2 months in the
      hemolytic group and 3.1 months in the nonhemolytic group. Serial brainstem
      auditory evoked potential assessments were performed until 2 years of age (3 in
      the hemolytic group and 18 in the nonhemolytic group). All had regular physical,
      neurologic, visual, and auditory evaluation until 3 years of age. The rate of
      exchange transfusion was significantly higher in the hemolytic group than in the
      nonhemolytic group (P < .05). Brainstem auditory evoked potential abnormalities
      at the initial assessment occurred in three (10.4%) in the hemolytic group (all
      related to ABO incompatibility) and nine (9.1%) in the nonhemolytic group. At 2
      years, the brainstem auditory evoked potential returned to normal except in three
      cases with a slightly increased hearing threshold (one [3.5%] in the hemolytic
      group at 60 dB nHL and two [2%] in the nonhemolytic group at 50 dB nHL]). There
      were no significant differences in the rate of brainstem auditory evoked
      potential abnormalities at the initial or subsequent assessments between both
      groups. All except five cases had a normal neurodevelopmental outcome at 3 years
      (three [two with ABO incompatibility and one with glucose-6-phosphate
      dehydrogenase deficiency] in the hemolytic group [10.4%] and two [2%] in the
      nonhemolytic group). All had mild motor delay and hypotonia, which returned to
      normal at 3 years. The rate of abnormal neurodevelopmental outcome was higher in
      the hemolytic group than in the nonhemolytic group, although with no significant
      difference between both groups (P = .08). All five cases in both groups with
      abnormal neurodevelopment had a normal brainstem auditory evoked potential at the
      initial assessment. There was no relationship between the abnormal initial
      brainstem auditory evoked potential and the final neurodevelopmental outcome. The
      toxic effect of hyperbilirubinemia on the auditory brainstem pathway and
      neurodevelopmental status in our cohort was transient. The prognosis of neonatal
      hemolytic hyperbilirubinemia in our Chinese cohort is excellent, possibly owing
      to an aggressive early-intervention approach.

PMID- 16948931
TI  - Long-term use of oxcarbazepine oral suspension in childhood epilepsy: open-label
      study.
AB  - Studies designed specifically for the pediatric population are needed to assess
      the tolerability and safety of the new antiepileptic drugs. The purpose of this
      study was to document the safety, ease of dosing, and acceptance of oxcarbazepine
      oral suspension in pediatric patients in monotherapy and polytherapy. A
      prospective, multicenter, open-label study was conducted at the neurology
      services of three pediatric university hospitals over 12 months. After obtaining
      signed informed consent, we enrolled a series of 62 patients with epilepsy aged
      between 2 months and 14 years who began oxcarbazepine treatment in monotherapy or
      in combination with other antiepileptic drugs to assess the seizure frequency,
      safety (adverse events), and acceptance of the pharmaceutical form by the
      patient's family. Fifty patients (80.6%) reduced seizures by at least 50%, 44
      (71%) saw a reduction in seizure frequency of over 75%, and 29 (46.8%) were
      seizure free at the end of the study. The difference in the number of seizures
      before and after the study was statistically significant, both overall and by
      type of pathology. Adverse events occurred in four patients (6.4%) and required
      withdrawal of the drug in two cases (skin rash); three patients (4.8%) withdrew
      for inefficacy. Five patients (8.1%) withdrew from the treatment. We concluded
      that, in this series of patients, oxcarbazepine in oral suspension form was seen
      to help reduce seizure frequency, to have few side effects, and to be accepted by
      parents and patients.

PMID- 16948932
TI  - Clinical and imaging study of human immunodeficiency virus-1-infected youth
      receiving highly active antiretroviral therapy: pilot study using magnetic
      resonance spectroscopy.
AB  - In the initial assessment of children with new-onset seizures, the suggestion
      that electroencephalography (EEG) should be standard and that magnetic resonance
      imaging (MRI) should be optional has been questioned. The purposes of this
      children (four boys) with vertically transmitted stable HIV infection had a
      neurologic examination, neuropsychologic testing, and a neuroimaging study. The
      structural magnetic resonance imaging (MRI) and metabolic changes (magnetic
      resonance spectroscopy) were compared with the cognitive, clinical, and
      laboratory results. Our results for the eight children who completed the magnetic
      resonance spectroscopic study showed that a high N-acetylaspartate (NAA) to
      choline ratio correlated significantly with IQ subtests of arithmetic (r = .74; P
      < .034) and comprehension (r = .77; P = .025). Our results suggest that lower NAA
      and higher choline values represent neuronal dysfunction and inflammation that
      can be recognized before anatomic changes appear on MRI. In addition, a low NAA
      to Cho ratio correlated with poor performance. These data suggest that magnetic
      resonance spectroscopy can be used as a follow-up tool in addition to the
      structural MRI. Moreover, a change in a child's performance with a concomitant
      change in NAA and choline, as measured with magnetic resonance spectroscopy,
      could indicate the need for more aggressive intervention.

PMID- 16948933
TI  - Magnetic resonance imaging (MRI) and electroencephalographic (EEG) findings in a
      cohort of normal children with newly diagnosed seizures.
AB  - In the initial assessment of children with new-onset seizures, the suggestion
      that electroencephalography (EEG) should be standard and that magnetic resonance
      imaging (MRI) should be optional has been questioned. The purposes of this study
      were to (1) describe the frequency of EEG and MRI abnormalities and (2) explore
      relationships between MRI and EEG findings to determine their relevance in the
      assessment of children with new-onset seizures who are otherwise developing
      normally. As part of an ongoing, prospective study of children with new-onset
      seizures, we studied 181 children (90 girls and 91 boys). Children were entered
      into the study within 3 months of their first-recognized seizure. The association
      between EEG and MRI abnormalities was explored using a chi-square test. Abnormal
      MRI findings were found in 32.6% (n = 59) of the sample. The EEG and MRI results
      agreed with respect to classification into normal or abnormal in 37% (n = 67). Of
      the 50 children with a normal EEG, however, 21 (42%) were found to have an
      abnormal MRI. We found an unexpectedly high frequency of imaging abnormalities in
      our sample of otherwise normal children, although the significance of these
      findings is not clear. Follow-up of these patients will help us interpret the
      importance of the abnormalities. Despite our relatively small sample, however,
      our findings indicate that a normal EEG does not reliably predict a normal MRI in
      children with first seizures.

PMID- 16948934
TI  - Stiripentol in childhood partial epilepsy: randomized placebo-controlled trial
      with enrichment and withdrawal design.
AB  - Stiripentol, a new antiepileptic drug inhibiting cytochrome P450-enzymes,
      suggested some efficacy when combined with carbamazepine in an open trial in
      refractory partial epilepsy of childhood. Our objective was to test these results
      in a placebo-controlled trial. To limit the number of patients included, we used
      an enrichment and withdrawal design. Among the 67 children entered in a 4-month
      open add-on stiripentol study following a 1-month single-blind placebo baseline,
      the 32 responders were randomized for 2 months either to continue stiripentol (n
      = 17) or to withdraw to placebo (n = 15). If seizures increased by at least 50%
      after randomization compared with baseline, the patients dropped out (primary end
      point): there were six patients on stiripentol and eight patients on placebo (not
      significant). However, a decrease in seizure frequency compared with baseline
      (secondary end point) was greater on stiripentol (-75%) than on placebo (-22%) (P
      < .025). Twelve patients experienced at least one adverse event on stiripentol
      (71%) compared with four patients on placebo (27%); none were reported as severe.
      The combination of stiripentol and carbamazepine proved to reduce seizure
      frequency in children with refractory partial epilepsy, although it failed to
      show a significant impact according to the escape criteria selected as the
      primary end point in the present study, for ethical reasons.

PMID- 16948935
TI  - Visuomotor tracking related to attention-deficit hyperactivity disorder (ADHD).
AB  - Deficient visuomotor tracking in children with attention-deficit hyperactivity
      disorder (ADHD) has been described, but the specific influence of attention on
      this deficit has not yet been elucidated. The present study compares visuomotor
      tracking under different conditions of attentional loading in children with ADHD
      with that of age-matched controls. A computerized visuomotor attentional tracking
      test that incorporated several levels of distraction was administered to 13
      typical children. The same test, as well as a standard Matching Familiar Figures
      Test and the Proteus Maze test, was administered to 32 children with ADHD and 21
      control children. Significant differences between children with ADHD and controls
      in visuomotor attentional tracking indices that relate to pacing and the accuracy
      of the tracking movements were observed under all levels of distraction. In
      parallel, a significant performance decrement was observed in all subjects once
      distraction was introduced. Discriminant analysis, based on the visuomotor
      attentional tracking test findings, resulted in correct classification of 92.3%
      of the typical children and 46% of the children with ADHD. Significant
      correlations between Matching Familiar Figures Test latency, as well as errors
      and visuomotor attentional tracking indices, were noted among children with ADHD
      when the visuomotor attentional tracking did not involve distraction. Under
      distraction, these correlations extended to the control group as well. In
      conclusion, visuomotor tracking appears to reflect the availability of
      attentional resources in general and is significantly affected by the presence of
      ADHD in particular. These results have potential implications related to the
      evaluation of children with ADHD on and off drugs.

PMID- 16948937
TI  - Childhood mesial temporal sclerosis.
AB  - The prevalence and clinical characteristics of mesial temporal sclerosis have not
      been well studied in children. All brain magnetic resonance imaging (MRI) reports
      of children less than 14 years of age were reviewed from two tertiary
      institutions. A 52-month period from one institution and a 37-month period from
      the other were reviewed. All reports of definite or possible mesial temporal
      sclerosis were noted. These patients' MRIs were then reviewed to confirm the MRI
      diagnostic criteria of mesial temporal sclerosis. The charts of the patients who
      satisfied these criteria were reviewed in detail. Three thousand one hundred
      brain MRI reports were reviewed. Twenty-six reports of mesial temporal sclerosis
      were found. Twenty-four of the 26 films satisfied the criteria of mesial temporal
      sclerosis by MRI after the films were reviewed. The prevalence among all
      pediatric brain MRI studies was 0.77%. All patients had presented with seizures,
      that is, there were no "incidental" findings of mesial temporal sclerosis. Four
      patients had a history of febrile seizures. Mesial temporal sclerosis is an
      uncommon finding in children, but when it occurs, it is always associated with
      epilepsy. Asymptomatic mesial temporal sclerosis or mesial temporal sclerosis not
      associated with a seizure disorder did not occur in our series. Febrile seizures
      can occur in association with mesial temporal sclerosis presenting in childhood.

PMID- 16948936
TI  - Sequence analysis of the structural nuclear encoded subunits and assembly genes
      of cytochrome c oxidase in a cohort of 10 isolated complex IV-deficient patients
      revealed five mutations.
AB  - The mitochondrial oxidative phosphorylation system is composed of five
      multiprotein complexes. The fourth complex of this system, cytochrome c oxidase
      (complex IV), consists of 13 subunits: 3 encoded by mitochondrial DNA and 10
      encoded by the nuclear genome. Patients with an isolated complex IV deficiency
      frequently harbor mutations in nuclear genes encoding for proteins necessary for
      the assembly of the complex. Strikingly, until now, no mutations have been
      detected in the nuclear encoded structural subunits of complex IV in these
      patients. We report the results of a mutational analysis study in patients with
      isolated complex IV deficiency screened for mutations in all structural genes as
      well as assembly genes known to cause complex IV deficiency. Four patients
      carried mutations in the complex IV assembly gene SURF1. One patient harbored a
      mutation in the COX10 gene involved in heme A synthesis. Mutations in the 10
      nuclear encoded structural genes were not present.

PMID- 16948938
TI  - Longitudinal assessment of neuropsychologic and language function in children
      with benign rolandic epilepsy.
AB  - Previous studies of benign rolandic epilepsy have reported improvement in
      cognitive functioning over time. Their focus was the impact of paroxysmal
      electroencephalographic (EEG) activity on neuropsychologic function.
      Comprehensive longitudinal language assessment has not previously been
      undertaken. In a cross-sectional study, we demonstrated that some children with
      benign rolandic epilepsy have difficulties in verbal and visual memory and
      phonologic awareness. The current study evaluated a subgroup longitudinally to
      determine if difficulties improved. Twenty-eight patients underwent comprehensive
      longitudinal neuropsychologic and language assessments. The clinical features
      evaluated included seizure frequency, absolute age, medications, and a follow-up
      EEG. Differences in performance were analyzed using t-tests. Improvement in
      cognitive functioning, particularly in the areas of verbal memory, receptive
      language ability, and phonemic manipulation, was demonstrated. Visual memory and
      aspects of phonologic awareness showed no change. The improvements were not
      related to the clinical variables. It is important to recognize cognitive
      difficulties in children with benign rolandic epilepsy. Some difficulties can
      resolve; however, continued monitoring, particularly in areas of visual memory
      and phonologic awareness, is required.

PMID- 16948939
TI  - Pontobulbar palsy and neurosensory deafness (Brown-Vialetto-van Laere syndrome)
      with hyperintense brainstem nuclei on magnetic resonance imaging: new finding in
      three siblings.
AB  - Three siblings (one boy and two girls) with Brown-Vialetto-van Laere syndrome are
      reported. A peculiar feature of onset with hearing loss in a patient with
      multiple cranial nerve palsies and a positive family history suggests this
      diagnosis. In our family, an autosomal recessive mode of inheritance was seen. In
      addition, we observed that early onset was associated with rapid deterioration
      and death. Optic nerve involvement and hyperintensity of the brainstem nuclei on
      magnetic resonance imaging (MRI) are two new features described in this report.

PMID- 16948940
TI  - Reversible posterior leukoencephalopathy and Adie's pupil after measles
      vaccination.
AB  - Reversible posterior leukoencephalopathy syndrome is an increasingly recognized
      disorder with typical radiologic findings of bilateral gray- and white-matter
      abnormalities in the posterior regions of the cerebral hemispheres. The majority
      of patients with reversible posterior leukoencephalopathy syndrome are adults,
      and it is rare in children. Previously reported associations of reversible
      posterior leukoencephalopathy syndrome include hypertension, vasculitis,
      nephrotic syndrome, severe hypercalcemia, hemolytic uremic syndrome, eclampsia,
      renal failure, and use of immunosuppressive drugs. Adie's pupil is described as
      the presence of a large unilateral or bilateral tonic pupil related to virus
      infections or trauma. In this article, we describe a case of reversible posterior
      leukoencephalopathy and Adie's pupil association that occurred after measles
      vaccination. To our knowledge, this association has not been reported.

PMID- 16948941
TI  - Deletion of the long arm of chromosome 6: report on a new case with intractable
      epilepsy.
AB  - Interstitial deletions in the terminal region of chromosome 6 are rare. The
      deletion most often occurs de novo. Mental retardation is always described. The
      most characteristic manifestations are microcephaly, micrognathia, hypotonia,
      typical facial appearance, strabismus, and congenital heart defects. Although
      this chromosomal syndrome does not appear to have a distinctive phenotype,
      epileptic seizures are uncommon in affected individuals. We report on a novel
      finding in a patient with the 46 XX karyotype and del(6)(q25-q26) who developed
      intractable epilepsy.

PMID- 16948942
TI  - Familial robertsonian 13;14 translocation with mental retardation and epilepsy.
AB  - Familial reports of a robertsonian translocation in more than two generations are
      rare. We report three generations (a daughter, the mother, and the mother's
      father) with a heterozygous, balanced robertsonian translocation
      t(13;14)(q11;q11). Central nervous system disease was present, but differentially
      expressed, in generations I and III. The daughter presented with mental delay and
      epilepsy, and the mother was apparently healthy, whereas the mother's father was
      again symptomatic, with borderline intelligence. Fluorescent in situ
      hybridization analysis was performed to exclude a loss or gain of chromosomal
      material. No uniparental disomy was present. We concluded that genetic counseling
      in the presence of this rearrangement was extremely difficult, independent of the
      affected parent being symptomatic or asymptomatic.

PMID- 16948943
TI  - Bickerstaff brainstem encephalitis associated with Mycoplasma pneumoniae
      infection.
AB  - Bickerstaff brainstem encephalitis is a clinical syndrome of ophthalmoplegia,
      cerebellar ataxia, and central nervous system signs and is associated with the
      presence of anti-GQ1b antibodies. There is a clinical continuum between
      Bickerstaff brainstem encephalitis and Miller Fisher syndrome. We describe the
      case of an 11-year-old boy with encephalopathy, external ophthalmoplegia,
      brainstem signs, and ataxia with raised titers of anti-GQ1b antibodies. He
      presented following a respiratory illness and had laboratory evidence of recent
      infection with Mycoplasma pneumoniae. M pneumoniae infection has been associated
      with both Bickerstaff brainstem encephalitis and Miller Fisher syndrome. This is
      only the second case in the literature of Bickerstaff brainstem encephalitis with
      raised titers of anti-GQ1b antibodies described in association with M pneumoniae
      infection. The patient responded to intravenous immunoglobulin administration.

PMID- 16948944
TI  - Coexistence of childhood absence and rolandic epilepsy.
AB  - The coexistence of absence and rolandic epilepsy is extremely rare. This
      coexistence has been attributed to either the treatment or an atypical course of
      the disease. However, for some authors, this issue remains controversial. We
      report the case of a 9-year-old girl presenting with both absence seizures and
      focal seizures consistent with rolandic epilepsy.

PMID- 16948945
TI  - Metabolic syndrome manifestations in Cohen syndrome: description of two new
      patients.
AB  - We report on sporadic cases that have the proposed diagnostic criteria for Cohen
      syndrome associated with metabolic syndrome. The patients, aged 14 and 16 years,
      had truncal obesity, mild mental retardation, hypotonia, narrow hands and feet, a
      high-arched palate, prominent upper central incisors, a high nasal bridge, and
      ocular abnormalities. Both had impaired glucose tolerance, with marked
      hyperinsulinemia exhibited by an oral glucose tolerance test. Moreover, they had
      the other metabolic syndrome features of hyperlipidemia and hypertension. We
      suggest that it is necessary to consider the possibility of metabolic syndrome in
      a case of Cohen syndrome.

PMID- 16948946
TI  - Hemiconvulsion-hemiplegia-epilepsy syndrome as a presenting feature of L-2
      hydroxyglutaric aciduria.
AB  - L-2-hydroxyglutaric aciduria was diagnosed in a 9-month-old female infant after a
      complex febrile convulsion with subsequent transient left-sided hemiplegia. The
      symptoms were consistent with acute hemiconvulsion-hemiplegia-epilepsy syndrome.
      Magnetic resonance imaging (MRI) of the brain revealed distinct white-matter
      abnormalities in the bifrontal and bioccipital periventricular area and increased
      signal intensity in the lenticular, caudate, and dentate nuclei, consistent with
      L-2-hydroxyglutaric aciduria. Increased concentrations of L-2-hydroxyglutaric
      acid were detected in the urine, plasma, and cerebrospinal fluid. The patient was
      homozyous for the p.Lys81Glu (c.241A>G) missense mutation in the L-2-HGA gene,
      confirming the diagnosis of L-2-hydroxyglutaric aciduria. Acute hemiconvulsion
      hemiplegia-epilepsy syndrome has not been reported as a presenting feature in L-2
      hydroxyglutaric aciduria. In patients with prolonged or complicated febrile
      seizures such as hemiconvulsion-hemiplegia-epilepsy syndrome, L-2-hydroxyglutaric
      aciduria should be included in the differential diagnosis, especially in children
      with concomitant macrocephaly.

PMID- 16948947
TI  - Diagnosis and molecular characterization of non-classic forms of Tay-Sachs
      disease in Brazil.
AB  - Molecular analysis of five Brazilian families, including eight patients
      presenting with nonclassic Tay-Sachs disease, was performed to identify frequent
      causative mutations and their correlation with clinical course. Three patients
      were affected by the B1 subacute variant and were shown to carry the R178H
      mutation (the DN allele), which is also common among Portuguese patients. Two of
      them were compound heterozygotes, whereas the third presented with the mutation
      in both alleles. Since Brazil was a Portuguese colony for over two centuries,
      common ancestry might be the probable explanation. The fourth patient presented
      with a juvenile phenotype and carries the R499H mutation, which has been reported
      only once worldwide and is associated with residual enzyme activity, responsible
      for a slower clinical course. The fifth family, of an Ashkenazi Jewish
      background, showed an extensive intrafamilial clinical variability among three
      affected sibs presenting with muscle atrophy, ataxia, and psychiatric symptoms.
      They were first diagnosed as having atypical spinal muscular atrophy and,
      subsequently, spinocerebellar ataxia, but, recently, the diagnosis of late-onset
      Tay-Sachs disease was confirmed based on reduced plasma hexosaminidase A activity
      and the G269S/InsTATC1278 genotype. It is therefore highly recommended to test
      patients with a similar clinical history for Tay-Sachs disease. In the same
      family, one first cousin committed suicide at the age of 24 years, presenting
      with a clinical phenotype that suggested an undiagnosed case and highlighting the
      effect of the intrafamilial clinical variability in delaying a prompt diagnosis.
      It is now recognized that his parents are, in fact, a carrier couple.
      Additionally, another relative had been previously identified as a heterozygote
      in a Tay-Sachs disease screening program, but the information was not shared
      among the family. Since this information might anticipate diagnosis and genetic
      counseling, it is advisable that heterozygote screening programs encourage
      families to share genetic information.

PMID- 16948948
TI  - Functional brain imaging in Sydenham's chorea.

PMID- 16948949
TI  - Patient with actin aggregate myopathy and not formerly identified ACTA1 mutation
      is heterozygous for the Gly15Arg mutation of ACTA1, which has previously been
      associated with actinopathy.

PMID- 16948950
TI  - Mutation in ROBO3 gene recently documented in patients with horizontal gaze palsy
      with progressive scoliosis.

PMID- 16948951
TI  - Humanism in medicine from the perspective of the Arnold Gold Foundation:
      challenges to maintaining the care in health care.

PMID- 16948952
TI  - Hepatobiliary cancers. Clinical practice guidelines in oncology.

PMID- 16948953
TI  - Can therapy of hepatitis C affect the development of hepatocellular carcinoma?
AB  - Chronic inflammation induced by viral infections and their role in carcinogenesis
      is well recognized. Two hepatotropic viruses, hepatitis B and hepatitis C (HCV),
      have been linked worldwide to the development of hepatocellular carcinoma (HCC).
      Although orthotopic liver transplant offers the best chance for cure and long
      term survival, the demand for organs far outweighs the supply. The incidence of
      HCC in the United States has increased over the past 3 decades. HCV-induced
      cirrhosis is believed to play a significant role in the rising rate of HCC.
      Therefore, primary measures to prevent HCC in HCV-infected patients are urgently
      needed. Numerous studies of the HCV HCC patient have considered primary treatment
      with interferon-based therapy. However, secondary prevention currently seems to
      carry more promise. This article evaluates and assesses various treatments for
      primary and secondary chemoprevention in the setting of HCV.

PMID- 16948954
TI  - Liver transplantation for hepatocellular carcinoma: an update.
AB  - Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death
      worldwide and the most common primary hepatic malignancy. It arises on a
      background of hepatic cirrhosis in approximately 95% of the cases in the United
      States. A wide variety of treatment modalities have been applied in the treatment
      of HCC. Liver transplantation has emerged as the preferred treatment for patients
      with small HCC. Transplantation for patients whose tumors do not exceed the Milan
      criteria yields results equivalent to those of transplantation for non-HCC
      indications. Controversy now exists regarding the use of living donors, expansion
      of selection criteria, and role of adjuvant therapy.

PMID- 16948955
TI  - Liver-directed therapies for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a major cause of cancer-related death
      worldwide. This disease can be treated through several surgical and nonsurgical
      approaches. Although the only curative options for patients with HCC are surgical
      (resection or transplantation), most patients unfortunately present with advanced
      neoplastic disease or experience the effects of chronic liver disease, making
      surgical resection implausible. Several additional options are available for
      treating this population. Ablative therapies such as percutaneous ethanol
      injection, cryotherapy, radiofrequency ablation, laser ablation, and microwave
      hyperthermic ablation can be used with varying degrees of success. Transarterial
      chemoembolization can be used in patients with advanced disease or advanced
      chronic liver disease that cannot be treated with resection or ablation. This
      article explores the various liver-directed therapies, including surgical
      resection, and defines morbidity, mortality, and survival for each.

PMID- 16948956
TI  - Palliative care. Clinical practice guidelines in oncology.

PMID- 16948957
TI  - Integrating POLST into palliative care guidelines: a paradigm shift in advance
      care planning in oncology.
AB  - Because predicting and outlining guidance for all possible scenarios is
      difficult, advance directives are rarely sufficiently precise to dictate patient
      preferences in specific situations as a disease progresses. Nonetheless, advance
      care planning is an essential process that should begin at the time of diagnosis,
      if not already initiated, to ensure that all patient and family rights are
      preserved. Communicating effectively with the patient and family and having the
      patient designate a surrogate decision-maker are critical. Attention must be paid
      to resolving conflicts among patient values and preferences and those of family
      and the health care team. Patient-centered goals for care and expectations should
      be elicited at first assessment and reassessed frequently as conditions change.
      As a disease progresses, advance directives are rarely precise enough to predict
      all possible scenarios and outline guidance for care. Therefore, for patients
      with advanced metastatic cancer and a potential life expectancy of less than 1
      year, converting patient-centered treatment goals into actionable medical orders
      while the patient maintains capacity is a more effective way to ensure that
      patient preferences are honored. Physician Orders for Life-Sustaining Treatment
      (POLST) and similar medical order forms provide explicit direction about
      resuscitation status ("code status") if the patient is pulseless and apneic.
      POLST also includes directions about additional interventions the patient may or
      may not want. A decade of research in Oregon has proved that the POLST Paradigm
      Program more accurately conveys end-of-life preferences that are more likely to
      be followed by medical professionals than traditional advance directives alone.

PMID- 16948958
TI  - Are your patients with risk of CVD getting the viscous soluble fiber they need?
AB  - A diet that includes 5 to 10 g/d of viscous soluble fiber reduces cardiovascular
      disease (CVD) events and death independent of baseline risk. Consuming foods rich
      in viscous soluble fiber reduces low-density lipoprotein cholesterol (LDL-C)
      blood levels 10% to 15% with expected reduction in CVD events by 10% to 15%.
      Routinely counsel adults at risk of CVD to promote a healthy diet: assess dietary
      fiber consumption; recommend specific foods rich in viscous soluble fiber;
      monitor LDL-C levels and encourage increased dietary fiber intake at follow-up
      visits; motivate patients to comply with recommendations.

PMID- 16948959
TI  - Psyllium: keeping this boon for patients from becoming a bane for providers.

PMID- 16948960
TI  - Two students, 2 tropical beaches, 2 injured feet.

PMID- 16948961
TI  - How might acknowledging a medical error promote patient safety?

PMID- 16948962
TI  - What hope is there for meaningful tort reform to stop another malpractice crisis?

PMID- 16948963
TI  - Acute sinusitis: which factors do FPs believe are most diagnostic and best
      predict antibiotic efficacy?

PMID- 16948964
TI  - Clinical inquiries. What test is the best for diagnosing infectious
      mononucleosis?
AB  - Tests for antibodies to Epstein-Barr viral capsid antigen or Epstein-Barr nuclear
      antigen are the most sensitive, are highly specific, and are also the most
      expensive for diagnosing infectious mononucleosis (strength of recommendation
      [SOR]: C, based on validating cohort study). Heterophile antibody tests have
      similar specificity and are cheaper, but are less sensitive in children or in
      adults during the early days of the illness (SOR: C, based on validating cohort
      study). The polymerase chain reaction assay for Epstein-Barr virus DNA is more
      sensitive than the heterophile antibody test in children, is highly specific, but
      is also expensive (SOR: C, based on validating cohort study). The percentages of
      atypical lymphocytes and total lymphocytes on a complete blood count provide
      another specific and moderately sensitive, yet inexpensive, test (SOR: C, based
      on validating cohort study).

PMID- 16948965
TI  - Clinical inquiries. What nonpharmacological treatments are effective against
      common nongenital warts?
AB  - Cryotherapy has similar cure rates to topical salicylate (a pharmacologic
      therapy) for nongenital common warts (strength of recommendation [SOR]: B, based
      on systemic review of variable quality randomized trials). Duct tape may be
      equivalent to cryotherapy (SOR: B, based on a single randomized trial). CO2
      laser, photodynamic therapy, pulsed dye laser (PDL), and Er:Yag laser therapies
      may also be effective for recalcitrant warts (SOR: C, based on observational
      cohort studies).

PMID- 16948966
TI  - Clinical inquiries. What are appropriate screening tests for infants and
      children?
AB  - There is adequate evidence for screening neonates for hemoglobinopathies,
      congenital hypothyroidism, phenylketonuria (strength of recommendation [SOR]: A),
      and cystic fibrosis (SOR: B). Vision screening should be done for those younger
      than age 5 years (SOR: B). High-risk children should be tested for tuberculosis
      (TB) (SOR: B) and lead toxicity (SOR: B). Few data exist to guide frequency and
      timing of these screening tests, so the following timing recommendations are
      based on consensus opinion (SOR: C): test for visual acuity yearly starting at
      age 3 years; test for TB and lead once between the ages of 9 and 12 months, and
      repeat for high risk or exposure.

PMID- 16948967
TI  - Clinical inquiries. Should patients receive 23-valent pneumococcal vaccination
      more than once?
AB  - No patient-oriented evidence supports pneumococcal revaccination of any patient
      (high-risk or otherwise). Antibody levels may be augmented by revaccination;
      however, the clinical efficacy of revaccination, even among high-risk patients,
      is unknown. Revaccination is recommended by the Advisory Committee on
      Immunization Practices (ACIP) in certain circumstances (strength of
      recommendation [SOR]: C, expert opinion based on physiology/bench research).
      Revaccination once appears to be safe, especially if provided 5 years or more
      after primary vaccination (SOR: B, based upon consistent results of cohort
      studies and nonrandomized prospective trials).

PMID- 16948968
TI  - Clinical inquiries. What is the most beneficial diet for patients with
      diverticulosis?
AB  - A diet high in fiber (particularly fruit and vegetable fiber) and low in fat and
      red meat may help to decrease the risk of symptomatic diverticular disease
      (strength of recommendation [SOR]: C, case-control studies and a large
      prospective cohort study). For people with diverticular disease, a diet high in
      fiber might decrease the risk of complications (SOR: C, case series). No studies
      have evaluated the effect of nut and seed avoidance.

PMID- 16948969
TI  - Clinical inquiries. What predicts a successful smoking cessation attempt?
AB  - Quit date abstinence (strength of recommendation [SOR]: B, based on low-quality
      randomized controlled trial [RCT] of healthy subjects) and refraining from
      tobacco products within the first 2 weeks after an attempt (SOR: A, based on 2
      RCTs) predict long-term abstinence from smoking. Inconsistent studies variously
      identify being married, a diagnosis of coronary artery disease (CAD) within the
      past 2 years, a higher education level, advanced age, and social status (such as
      being a homeowner) as factors correlated with successful smoking cessation (SOR:
      C, based on prospective cohort studies with conflicting results). Smoking
      cessation rates increase in a dose-response relationship with minutes per
      counseling session, number of counseling sessions, and total minutes of
      counseling time (SOR: A, based on good-quality meta-analyses). Among counseling
      techniques, providing smokers with practical counseling (problem-solving skills),
      providing social support as part of treatment, helping smokers obtain social
      support outside of treatment, and use of aversive smoking interventions (eg,
      rapid smoking) seem to be efficacious (SOR: B, based on limited-quality meta
      analyses).

PMID- 16948970
TI  - [International consensus and recommendations on cardiopulmonary resuscitation
      (2005)].

PMID- 16948971
TI  - [Estimation of the prevalence of cerebral palsy in the Autonomous Community of
      Castilla y Leon (Spain) using a disabilities register].
AB  - INTRODUCTION: The prevalence of cerebral palsy in Western countries is estimated
      to be around 2 cases/1,000 inhabitants. The objective of this study was to
      estimate the prevalence of cerebral palsy in the Autonomous Community of Castilla
      y Leon and to assess potential differences among the nine provinces of this
      region. PATIENTS AND METHODS: The number of patients with CP in 1999, separated
      by provinces and by age groups, was obtained from the Community Sectorial Program
      for Persons with Disabilities. These data originally came from handicap
      evaluations carried out in each base center. Prevalences were calculated using
      population data from the National Institute of Statistics. RESULTS: A total of
      335 patients aged 0-13 years were registered as having a diagnosis of cerebral
      palsy in 1999. The prevalence of cerebral palsy was 1.05 cases/1,000 inhabitants
      aged 0-13 years. Statistically significant differences were found in the
      prevalence of cerebral palsy among provinces (p < 0.0001). The highest prevalence
      was found in Salamanca, with 1.87 cases/1,000 inhabitants, while the lowest
      prevalence was found in Segovia, with 0.33 cases/ 1,000 inhabitants. CONCLUSIONS:
      The prevalence of cerebral palsy in childhood in Castilla y Leon was lower than
      that reported in western countries. Substantial differences were found among
      provinces. The prevalence of cerebral palsy is probably underreported in some
      provinces. These differences could be due to a disparity in diagnostic criteria,
      especially in young children.

PMID- 16948972
TI  - [A randomized single-blind trial of the effects of vitamins C and E in familial
      hypercholesterolemia].
AB  - INTRODUCTION: The aim of this study was to evaluate the effect of antioxidant
      vitamin C and E administration on dyslipidemia, plasma fatty acid composition,
      and biochemical inflammatory markers in children with heterozygous familial
      hypercholesterolemia (FH). PATIENTS: Forty girls and boys with heterozygous FH,
      aged between 2 and 18 years, and with plasma low-density lipoprotein (LDL)
      cholesterol levels higher than 160 mg/dl were studied. METHODS: We performed an
      open longitudinal randomized trial over a 1-year period. All children followed a
      dietary intervention according to the National Cholesterol Education Program
      (NCEP)-1 guidelines and were randomized into two groups. One group (n = 21)
      received therapy with vitamin C (500 mg twice a day) and vitamin E (400 IU per
      day). A second group (n = 19) did not receive vitamin therapy. RESULTS: In
      patients receiving antioxidant vitamins, plasma linoleic acid levels (18:2 omega
      6) significantly increased and the essential fatty acid deficiency ratio
      significantly decreased (Mead/arachidonic acid: 20:4 omega-6/20:3 omega-9). No
      significant differences were observed in plasma lipid profile, adhesion
      molecules, or reactive C protein. CONCLUSIONS: Antioxidant vitamin therapy in
      children with heterozygous FH modifies the plasma fatty acid profile. These
      modifications are independent of the degree of dyslipidemia and may represent an
      indicator of reduced cardiovascular risk.

PMID- 16948973
TI  - [Neonatal tumors: clinical and therapeutic characteristics. Analysis of 72
      patients in La Fe University Children's Hospital in Valencia (Spain)].
AB  - BACKGROUND: Neonatal tumors, which represent only 1.5-2% of all pediatric tumors,
      have distinctive features. Their incidence is imprecise, as selection criteria
      vary and there are few published studies. OBJECTIVE: To analyze and disseminate
      findings on the histological, clinical, therapeutic and follow-up characteristics
      of neonatal tumors. MATERIAL AND METHODS: We performed a retrospective study of
      the clinical records of patients diagnosed with neonatal tumors in La Fe
      University Children's Hospital in Valencia (Spain) between January 1990 and
      December 1999. Hamartomas, flat and cavernous cutaneous hemangiomas, nevi,
      lipomas, subcutaneous fibroma, lymphangiomas, and epidermal cysts were excluded.
      A systematic review of the literature published in the previous 25 years was
      performed using Medline, Cancerlit, Index Citation Science, and Embase. The
      search profile combined neonatal or congenital and tumor or cancer or neoplasm.
      The most interesting studies, as well as the most relevant references contained
      in these studies and published before the search period, were selected. RESULTS:
      The clinical records of 72 patients with neonatal tumors (40 boys and 32 girls),
      representing 2.8% of all pediatric tumors, were reviewed. The most frequent
      tumors were hemangiomas (20.8%, 15 patients), neuroblastomas (16.7%, 12
      patients), teratomas (12.5 %, 9 patients), and soft tissue tumors (9.7 %, 7
      patients). Eighty-six percent of the patients were symptomatic during the first
      week of life. Although diagnosis was prenatal in 22.2 % of the patients, the most
      frequent findings on physical examination were identification of a mass or
      cutaneous lesion in 24 patients (33.3%) and an abdominal mass or hepatomegaly in
      13 patients (18%). An associated disease, malformation or syndrome was found in
      15 patients (20.8 %). Treatment included surgery (50% of patients) and drugs as
      monotherapy or coadjuvant therapy (13.9%). Thirteen patients received irradiation
      after the neonatal period. Spontaneous complete remission took place in six
      patients. Twenty patients died (27.8%). Mortality was highest in patients with
      central nervous system tumors or leukemias (83.3% and 75 % respectively). By
      contrast, none of the patients with hemangiomas or teratomas died. Mortality was
      low in patients with neuroblastoma (8.3%). At the time of the study, survival was
      73 %, with a median follow-up of 8 years. CONCLUSIONS: Due to their biological
      features, neonatal tumors represent a distinctive subgroup in pediatric
      oncohematology. The concept of neonatal tumor should be unified to allow the
      results of different research groups to be analyzed and compared. Despite the
      methodological limitations found, the clinical, diagnostic, therapeutic, and
      follow-up characteristics of our patients are similar to those of other published
      series. The differences found could be explained by the diverse selection
      criteria employed.

PMID- 16948974
TI  - [Identification of a new at-risk neonatal population by using Peruvian
      intrauterine growth curves].
AB  - OBJECTIVES: To quantify the increase in small for gestational age (SGA) neonates
      by using Tacna-Peru intrauterine growth curves and to study associated risk
      factors. MATERIAL AND METHODS: From 1995 through 2000 15,739 neonates were
      studied at the Hipolito Unanue Tacna Hospital by applying both Lubchenco and
      Tacna-Peru intrauterine growth curves; the additional SGA neonates identified by
      the Peruvian curves were classified as "new SGAs", and their risk factors were
      studied. The Perinatal Computer System, odds ratio and chi square test were used
      in the statistical analysis. RESULTS: When Lubchenco's and the Peruvian curves
      were applied, the percentage of large for gestational age (LGA) neonates
      decreased from 15.6 to 9.5 %, that of adequate for gestational age (AGE) neonates
      was similar at 83.2 and 81.3 % and that of SGA neonates increased from 1.2 to 9.2
      %; these changes were statistically significant. The Tacna-Peru curves identified
      1,448 SGA neonates, while Lubchenco's curves identified 189. The difference of
      1,259 neonates (8 % of the total population) corresponded to the group of "new
      SGA neonates". Risk factors were multiple pregnancy, heart disease, hypertensive
      disease of pregnancy, primiparity, and urinary infection; risks included
      increased morbidity, nutritional metabolic abnormalities, infections, congenital
      defects, moderate depression, and neonatal mortality. CONCLUSIONS: The results of
      the present study confirm that Lubchenco curves overestimate the number of LGA
      neonates and underestimate that of SGA neonates and are not suitable for use in
      Peruvian neonates. The new SGA group showed high morbidity and mortality. We
      recommend that perinatologists design and use curves specific to their
      populations.

PMID- 16948975
TI  - [Neonatal management in the emergency department of a tertiary children's
      hospital].
AB  - OBJECTIVE: To determinate the chief complaints in neonates presenting to a
      pediatric emergency service and their management. MATERIAL AND METHODS: We
      performed a retrospective study of patients younger than 28 days old who
      presented to the pediatric emergency department in 2003. Patients directly
      admitted to the neonatal unit and those attended by the surgery and orthopedic
      surgery departments were excluded. Information on sex, age, time and date,
      waiting time, visit duration, source of referral, presenting complaint,
      complementary examinations, final diagnosis, and hospital admission were
      analyzed. RESULTS: There were 1,481 neonatal visits. The mean chronological age
      was 15.8 days and 57.3 % were boys. Visits were most frequent on Fridays, evening
      shifts, and in July and December. The most frequent chief complaints were
      crying/irritability (16.3 %), fever (13.6 %), vomiting (11 %), and influenza
      (10.8 %). The most frequent final diagnoses were feeding problems (12.6 %),
      infantile colic (12.4 %), and upper respiratory tract infections (12 %). No
      abnormalities were detected in 11.7 % of the patients and complementary
      examinations were not required in 45.9 %. The admission rate was 26 %, most
      commonly due to fever and bronchiolitis. CONCLUSIONS: Many visits were due to
      minor problems that did not require complementary examinations and could have
      been resolved in primary care. Because of the greater vulnerability of this age
      group, thorough investigation is required to rule out severe disease. This
      phenomenon was reflected by the large number of complementary examinations and
      admissions.

PMID- 16948976
TI  - [Normal thyroid-stimulating hormone levels in screening for congenital
      hypothyroidism in newborn twins].
AB  - INTRODUCTION: A large number of articles have been published since neonatal
      screening for congenital hypothyroidism (CH) started in the 1970s. Surprisingly,
      little information on false negative results in these screenings has been
      reported. PATIENTS AND METHODS: Thyroid-stimulating hormone (THS) levels were
      determined in 360,651 newborn infants in Malaga until March 2005. One hundred and
      fifty-six CH cases were detected, of which 86 % were permanent and 14 % were
      transient. In this study, we retrospectively analyzed a group of 13 CH dizygotic
      twins in which only one of the twins had CH. RESULTS: The first two patients were
      diagnosed late and data on whether they were included in neonatal screening were
      lacking. In seven of the 13 patients, TSH values were initially normal: five
      patients were diagnosed by a second test performed 14 days after birth and were
      treated before they were 1 month old, and two were diagnosed and treated late
      because a second test was not performed. In the remaining four patients, TSH
      values were initially elevated but were lower than confirmation test values.
      CONCLUSIONS: It is now widely accepted that thyroid function could be compensated
      between two dizygotic twins if only one of the twins has CH, leading to a false
      negative result. The results of the present study indicate the need to repeat the
      test for CH 14 days after birth in all dizygotic twins.

PMID- 16948977
TI  - [Congenital anatomic gastrointestinal obstruction: prenatal diagnosis, morbidity
      and mortality].
AB  - OBJECTIVES: To describe the morbidity and mortality associated with congenital
      gastrointestinal obstruction, assess the usefulness of prenatal diagnosis, and
      analyze the results in relation to the site of obstruction. PATIENTS AND METHODS:
      We performed a retrospective case series study of 148 patients in a 13-year
      period (1990-2003). Sites of obstruction was classified into three groups: I)
      gastric, duodenal or jejunal; II) ileal or colonic; III) anorectal. RESULTS:
      There were 65 patients in group I, 38 in group II and 45 in group III. Surgery
      was performed in 137 patients. Trisomy was diagnosed in 15 patients,
      polymalformation syndrome in 16 patients, and cystic fibrosis in seven patients.
      More than one site of intestinal obstruction was found in 22 patients (15 %).
      Morbidity consisted of nosocomial sepsis in 32 %, necrotizing enterocolitis in 7
      %, and short gut in 3.4 %. Prematurity (48 %) was associated with higher
      morbidity and mortality. Overall mortality was 14.2 %, mainly associated with
      other malformations and extraintestinal problems. When patients with other
      extraintestinal malformations were excluded, the highest mortality was found in
      group II (OR: 12.19; CI: 2.4-76.2). The overall sensitivity of prenatal diagnosis
      was 0.44 and the mean gestational age at diagnosis was 31.6 weeks (SD 5.2).
      According to the site of obstruction, sensitivity was 0.77 in group I, 0.39 in
      group II and 0.04 in group III. Prenatal diagnosis did not alter prognosis.
      CONCLUSIONS: Morbidity and mortality were strongly influenced by extraintestinal
      problems. The most severe intestinal complications were midgut volvulus and
      necrotizing enterocolitis. Prenatal diagnosis was late and showed good
      sensitivity only in group I.

PMID- 16948978
TI  - [Nephrolitiasis in a patient with cystic fibrosis].
AB  - Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance
      regulator (CFTR) gene. Defects in the CFTR gene cause abnormal chloride
      conductance across the apical membrane of epithelial cells, which results in
      progressive lung disease and also affects other organs. Because life expectancy
      has increased, other complications of CF have become more apparent. We present a
      patient with CF and symptomatic nephrolithiasis. Several stones were evident in
      both kidneys. A 24-hour urine sample showed hyperoxaluria (141 mg/24 h/ 1.73
      m(2)) and hypocitraturia and (206 mg/24 h/1.73 m(2), 177 mg citrate/g
      creatinine). Nephrolithiasis should be included in the differential diagnosis of
      patients with CF and abdominal pain; urinary excretion of oxalate and citrate
      should be investigated.

PMID- 16948979
TI  - [False negative diagnosis of HIV-1].
AB  - We report a case of a false negative diagnosis of HIV-1 infection in an African
      girl. Two HIV-1 DNA polymerase chain reaction (PCR) tests were negative at the
      second and fourth months of life. Because anti-HIV antibodies persisted when the
      patient was 18 months old, the HIV-1 RNA PCR test was performed with a positive
      result, confirming HIV-1 non-B subtype, recombinant A-G. The prevalence of non-B
      HIV-1 subtypes are increasing in Spain, which could be related to the phenomenon
      of immigration. Approximately one-third of HIV-infected foreigners have non-B
      subtypes and the percentage increases to 70 % of the African population in Spain.
      In non-B HIV-1 subtypes, false negative results and inconsistencies between viral
      load and CD4 count are more frequent. These subtypes also show a higher rate of
      resistance to protease inhibitors, which can have therapeutic implications.

PMID- 16948980
TI  - [Pediatric acute spinal cord injury].
AB  - INTRODUCTION: Pediatric acute spinal cord injury is rare but is often associated
      with significant disability and prolonged stay in the intensive care unit (ICU).
      OBJECTIVES: The main objective of this study was to determine the epidemiology,
      initial clinical abnormalities, diagnostic studies, treatment and outcome of
      acute spinal cord injuries in a tertiary level pediatric hospital. A second
      objective was to analyze whether early tracheostomy allows earlier discharge of
      these patients. PATIENTS AND METHODS: A retrospective analysis of patients with
      acute spinal cord injuries admitted to our pediatric ICU since 1992 was
      performed. RESULTS: We included 16 patients in the study, 12 of whom were boys
      (75 %). The patients were aged from birth to 19 years on admission to the ICU.
      The length of stay in the ICU was between 12 hours and 6 years. The cause of the
      lesion was birth trauma in four patients; one died and the remaining three live
      at home under mechanical ventilation. Traumatic injuries occurred in seven
      patients, two of whom died; a further two live in a long-term care facility and
      the remaining three live at home. Vascular spinal malformation occurred in two
      patients, and the three remaining injuries occurred during the acute
      postoperative period following spinal surgery. Of the 16 children, 56.2 % were
      tracheostomized and 83 % of the survivors live at home. CONCLUSIONS: Early
      tracheostomy, the availability of invasive ventilation for home use and parent
      education permit earlier discharge of these patients and allow more of them to
      live at home.

PMID- 16948981
TI  - [Littoral cell angioma and Von Willebrand's disease].

PMID- 16948982
TI  - [Early postnatal infection due to cytomegalovirus in an extremely low-birth
      weight premature infant].

PMID- 16948983
TI  - [Ocular filariasis due to Loa-loa. An emerging tropical parasitosis in Europe?].

PMID- 16948984
TI  - [Choristoma with gastric and respiratory heterotopy in a neonate].

PMID- 16948985
TI  - [Nevus comedonicus].

PMID- 16948986
TI  - [Lichen striatus in a dark-skinned patient].

PMID- 16948987
TI  - [Neck's deformity and elevation of the scapula].

PMID- 16948988
TI  - [Serum markers in idiopathic pulmonary fibrosis. Implications for prognosis].

PMID- 16948989
TI  - [Quantifying plasma levels of transforming growth factor beta1 in idiopathic
      pulmonary fibrosis].
AB  - OBJECTIVE: Transforming growth factor ss1 (TGF-ss1) is one of the key profibrotic
      mediators in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The purpose
      of this study was to investigate the prognostic value of quantifying TGF-ss1
      levels in patients with IPF. PATIENTS AND METHODS: We conducted a prospective
      study of 29 IPF patients and 27 healthy controls. Enzyme-linked immunosorbent
      assays were used to quantify TGF-ss1 levels. RESULTS: Mean (SD) TGF-ss1 levels
      were significantly higher in the IPF patients than in the control subjects (11.1
      [7.5] ng/mL vs 4 [2.4] ng/mL; P< .01). Weak inverse correlations were observed
      between TGF-ss1 levels and both forced vital capacity and total lung capacity.
      Thirteen IPF patients were evaluated at 8 (1.2) months (range, 5-9 months). The
      mean TGF-ss1 level was 18.2 (15) ng/mL and there were no significant differences
      with respect to the initial measurement of 11.1 (7.5) ng/mL. No correlation was
      observed between changes in respiratory function and changes in TGF-ss1 levels.
      CONCLUSIONS: Although plasma levels of TGF-beta1 were high in the patients with
      IPF, they do not appear to be a useful prognostic marker of disease activity or
      therapeutic response.

PMID- 16948990
TI  - [Effect of intravenous magnesium sulfate on chronic obstructive pulmonary disease
      exacerbations requiring hospitalization: a randomized placebo-controlled trial].
AB  - OBJECTIVE: Magnesium sulfate has been shown to have a bronchodilating effect in
      asthma, but this effect has not been clearly established in the context of
      chronic obstructive pulmonary disease (COPD). For this reason we investigated the
      possible bronchodilating effect of magnesium sulfate in COPD exacerbations.
      PATIENTS AND METHODS: We studied 24 patients with exacerbated COPD who required
      admission to our hospital's pneumology department. All patients underwent
      baseline spirometry and were subsequently randomized to groups in a double-blind
      crossover design. Patients received 1.5 g of magnesium sulfate or placebo in an
      intravenous solution for 20 minutes. Those who received magnesium sulfate the
      first day were given placebo the second day, and vice versa. Spirometry was
      performed 15, 30, and 45 minutes after administration of magnesium sulfate or
      placebo. Finally, 400 microg of salbutamol were administered using a spacer and a
      final spirometry was performed 15 minutes later. All patients also received
      treatment with corticosteroids, intravenous antibiotics, oxygen, and regularly
      scheduled bronchodilator therapy (salbutamol and ipratropium bromide every 6
      hours). RESULTS: When we compared absolute increase in milliliters and percentage
      increase in forced expiratory volume in 1 second (FEV1) obtained with magnesium
      sulfate application to the increases obtained with placebo after 15, 30, and 45
      minutes, no significant differences were found. When we compared absolute and
      percentage increases in FEV1 after administering salbutamol, we found
      significantly greater increases after magnesium sulfate administration. The mean
      (SD) absolute increase in FEV1 was 0.18 [corrected] (0.42) L after magnesium
      sulfate administration and 0.081 [0.01] L after placebo (P=.004). The percentage
      increase in FEV1 was 17.11% (3.7%) after magnesium sulfate and 7.06% (1.8%) after
      placebo (P=.008). CONCLUSIONS: Intravenous administration of magnesium sulfate
      has no bronchodilating effect in patients with COPD exacerbations. It does,
      however, enhance the bronchodilating effect of inhaled ss2-agonists.

PMID- 16948991
TI  - [Bacterial etiology of chronic bronchitis exacerbations treated by primary care
      physicians].
AB  - OBJECTIVE: Few studies have been carried out to determine the prevalence of
      microorganisms causing exacerbations of chronic bronchitis in the community
      setting. The aim of the present study was to determine the bacterial etiology of
      chronic bronchitis exacerbations in patients not requiring hospitalization.
      PATIENTS AND METHODS: This observational, cross-sectional, multicenter study was
      carried out at the primary care level during 2 weeks (in November 2001 and
      January 2002). All laboratory work was carried out at a single center. We studied
      1,947 patients with mild-moderate exacerbations treated by 650 primary care
      physicians. All the sputum samples received for centralized processing were
      subject to Gram staining, microscopic examination, and bacterial culture.
      RESULTS: Out of 1,537 cultures of sputum samples collected, 498 had good cell
      quality for microscopic examination (32.4%). Of the 498 good quality samples
      analyzed, 246 (49.4%) were positive and 468 isolates were obtained. The most
      commonly isolated germ was Streptococcus pneumoniae (163 cases, 34.8%), followed
      by Moraxella catarrhalis (112, 23.9%), and Haemophilus influenzae (59, 12.6%). In
      1.2% of the S. pneumoniae isolates resistance was found to amoxicillin;
      resistance to macrolides was found in 34.3%. The antibiotics most commonly
      prescribed, however, were macrolides (38.3% of the prescriptions). CONCLUSIONS:
      S. pneumoniae was the microorganism most frequently isolated in cases of chronic
      bronchitis exacerbation treatable in this outpatient setting.

PMID- 16948992
TI  - [Is endoscopic treatment of bronchopleural fistula useful?].
AB  - OBJECTIVE: New endoscopic techniques have been developed as an alternative to
      surgical treatment of bronchopleural fistula. The objective of this study was to
      analyze our experience with endoscopic treatment of such fistulas. MATERIAL AND
      METHODS: We conducted a retrospective study of patients with bronchopleural
      fistula diagnosed by fiberoptic bronchoscopy. Patient characteristics, underlying
      disease, fistula size, and outcome of endoscopic treatment were analyzed. The
      endoscopic technique consisted of injection of fibrin sealants (Histoacryl and/or
      Tissucol) through the catheter of the fiberoptic bronchoscope. RESULTS: Between
      1997 and 2004, 18 patients were diagnosed with bronchopleural fistula by
      fiberoptic bronchoscopy. All were men with a mean (SD) age of 62 (12) years.
      Bronchopleural fistula was diagnosed after neoplastic surgery in 16 patients, in
      the bronchial suture after lung transplantation in 1 patient, and concurrently
      with pleural effusion due to hydatidosis in the remaining patient. The size of
      the fistula ranged from 1 mm to 10 mm (mean 3.6 [2.7] mm). Fibrin sealants were
      applied in 14 patients, 2 underwent direct surgery after diagnosis, and the
      bronchopleural fistula closed spontaneously in the remaining 2. The fibrin
      sealant used was Histoacryl in 12 patients and Tissucol in 2. Pleural drainage
      was employed simultaneously and antibiotic therapy was administered at the
      discretion of the surgeon. The 4 patients whose bronchopleural fistula was
      associated with empyema also underwent pleural lavage. In 12 patients the
      fistulas closed as a result of the endoscopic technique (85.7%), and no
      complications were observed. For 85.7%, fewer than 3 applications of fibrin
      sealant were necessary. CONCLUSIONS: The success rate of closure of
      bronchopleural fistula with fibrin sealants injected under guidance with
      fiberoptic bronchoscopy is high and there are no complications. This technique
      can render surgery unnecessary.

PMID- 16948993
TI  - [Bronchioloalveolar carcinoma in Spain: a rare and different form of lung
      cancer].
AB  - OBJECTIVE: To describe a series of cases of bronchioloalveolar carcinoma (BAC)
      treated surgically between 1993 and 1997 in the 19 hospitals that make up the
      Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pulmonology
      and Thoracic Surgery (GCCB-S). PATIENTS AND METHODS: From a total of 2,944 cases
      of non-small cell lung cancer (NSCLC), 82 (3%) were BAC. The clinical
      characteristics and prognosis of patients with BAC were compared with those of
      the remaining 2,862 patients with NSCLC. RESULTS: The percentage of men was lower
      for BAC than for other types of NSCLC (64.6% compared with 93.5%; P< .001) and
      BAC was associated with less comorbidity (50% vs 62%; P< .05), particularly in
      terms of chronic obstructive pulmonary disease (33% vs 47.2%; P< .05). Other
      characteristics showing significant differences were the higher frequency of BAC
      as a chance finding and the lower likelihood of weight loss or reduced
      performance status at the time of diagnosis. Classification as stage cI was
      significantly more common in patients with BAC (87% vs 75%; P.001), and this
      difference between groups was more pronounced for stage pI (68.5% vs 47%; P<
      .01). Only taking into account patients classified as stage pI with complete
      resection of NSCLC and following exclusion of operative mortality, patients with
      BAC presented an overall 5-year survival of 65% (95% confidence interval [CI],
      51%-79%), compared with a significantly lower survival of 53% (95% CI, 50%-56%;
      P< .05) in patients with other forms of NSCLC. CONCLUSIONS: In Spain, among cases
      of lung cancer treated by surgery, BAC is very rare (3%) and displays clinical
      characteristics that are different from other forms of NSCLC. Controlling for the
      most basic prognostic factors (stage pI and complete resection), survival is
      significantly higher for BAC.

PMID- 16948994
TI  - [Nicotine replacement therapy during pregnancy].
AB  - In spite of the fact that smoking is the main cause of obstetric morbidity and
      mortality, 20% of North American women smoke during pregnancy. In Spain, this
      figure is as high as 30% to 35%. Treating smoking addiction in these patients
      should be the first and most important therapeutic measure undertaken by health
      professionals responsible for the care of pregnant women. All experts recommend
      the use of nicotine replacement therapy when more conservative treatments have
      failed. This article reviews the indications and contraindications for nicotine
      replacement therapy during pregnancy as well as other issues relating to the
      safety of this type of treatment.

PMID- 16948995
TI  - [Azygos vein aneurysm forming a mediastinal mass].
AB  - Aneurysm of the azygos vein is a rare cause of mediastinal mass that is normally
      detected radiologically in asymptomatic patients. In some cases a diagnosis is
      made by noninvasive methods, such as computed tomography and magnetic resonance.
      However, in the present case imaging revealed what appeared to be a solid mass.
      When the mass had been excised by thoracotomy, the histopathologic diagnosis was
      aneurysm of the azygos vein.

PMID- 16948996
TI  - [High-resolution computed tomography patterns of organizing pneumonia].
AB  - Organizing pneumonia is an uncommon lung disease with a wide variety of
      radiologic findings, few of which have been discussed in the literature. We
      performed high resolution computed tomography on 34 patients with a histological
      diagnosis of organizing pneumonia and studied the images they presented. Twenty
      five of the cases were idiopathic and 9 secondary. The findings observed were
      parenchymal consolidation (76%), ground glass opacity (59%), bronchial dilatation
      (53%), centrilobular nodules (35%), septal thickening (23%), halo sign (15%), and
      reversed halo sign (12%). Secondary cases presented more findings of septal
      thickening and fewer complete remissions.

PMID- 16948997
TI  - [Lithoptysis in a patient with primary ciliary dyskinesia].

PMID- 16948998
TI  - [Inappropriate antidiuretic hormone secretion in pulmonary nocardiosis].

PMID- 16948999
TI  - [Use of internet and electronic resources among Spanish intensivist physicians.
      First national survey].
AB  - OBJECTIVE: Estimate knowledge and use habits of different electronic resources in
      a sample of Spanish intensivists: Internet, E-mail, distribution lists, and use
      of portable electronic devices. DESIGN: Self-applied questionnaire. METHODS: A 50
      question questionnaire was distributed among Spanish intensivists through the
      hospital marketing delegates of a pharmaceutical company and of electronic
      forums. RESULTS: A total of 682 questionnaires were analyzed (participation:
      74%). Ninety six percent of those surveyed used Internet individually: 67%
      admitted training gap. Internet was the second source of clinical consultations
      most used (61%), slightly behind consultation to colleagues (65%). The pages
      consulted most were bibliographic databases (65%) and electronic professional
      journals (63%), with limited use of Evidence Based Medicine pages (19%). Ninety
      percent of those surveyed used e-mail regularly in the practice of their
      profession, although 25% admitted that were not aware of its possibilities. The
      use of E-mail decreased significantly with increase in age. A total of 62% of the
      intensivists used distribution lists. Of the rest, 42% were not aware of its
      existence and 32% admitted they had insufficient training to handle them. Twenty
      percent of those surveyed had portable electronic devices and 64% considered it
      useful, basically due to its rapid consultation at bedside. Female gender was a
      negative predictive factor of its use (OR 0.35; 95% CI 0.2-0.63; p=0.0002).
      CONCLUSIONS: A large majority of the Spanish intensivists use Internet and E
      mail. E-mail lists and use of portable devices are still underused resources.
      There are important gaps in training and infrequent use of essential pages. There
      are specific groups that require directed educational policies.

PMID- 16949000
TI  - [Epidemiology of acute kidney failure in Spanish ICU. Multicenter prospective
      study FRAMI].
AB  - OBJECTIVE: Multicenter study oriented at establishing the incidence and prognosis
      of acute kidney failure (AKF) in the ICU of our country. MATERIAL AND METHODS:
      Prospective study of adult patients admitted over 8 months in 43 Spanish ICUs to
      detect AKF defined as creatinine>or=2 mg/dl or diuresis<400 ml/24 hours (in
      chronic patients 100% increase of creatinine, excluding those with baseline
      creatinine>or=4 mg/dl). RESULTS: 901 episodes of AKF (AKF episodes (incidence
      5.7%), 55% of which occurred on admission. A total of 38.4% of the episodes were
      due to acute tubular necrosis (ATN), 36.6% to prerenal, and 21.2% to mixed. Renal
      depuration (RC) was required in 38%. Mortality was 42.3% during the AKF episode
      (34.1% in those who were admitted with AKF versus 50.9% in those who developed it
      after admission), 80% in patients with Hepatorenal Syndrome, 51.6% in ATN and
      29.9% in prerenal. We detect an independent relationship with mortality for age
      (OR 1.03), background of diabetes (OR 2.06), development of AKF in the ICU (OR
      2.51), oliguria (OR 5.76) and RC (OR 2.32). Recovery of the kidney function
      occurred in 85.6% of the survivors and RC was maintained in only 1.1% on
      discharge from the ICU. We calculated the area under the curve of APACHE II on
      admission (0.62), SOFA on onset of AKF (0.68), Liano index (0.7) and maximum SOFA
      (0.79). CONCLUSIONS: AKF in ICU patients does not show an elevated incidence but
      does have high mortality, presenting greater seriousness when it appears after
      admission. However, recovery is elevated in patients who survive. The usual
      prognostic indexes are not exact in this patient group, the ISA and maximum SOFA
      being those which shows a closer relationship with mortality.

PMID- 16949001
TI  - [Inflammatory response and apoptosis in acute pulmonary injury].
AB  - One of the principal mechanisms of pulmonary injury in acute respiratory distress
      is due to the effects of the precipitated inflammatory response. The damage
      produced to the alveolar epithelium and underlying endothelium depends on the
      sequestration and activation of inflammatory cells, which in turn exert their
      actions through mediators. On the other hand, apoptosis is a mechanism
      responsible for epithelial damage and regulation of inflammation. Response of the
      lung tissue subjected to mechanical ventilation stimulus is added to the previous
      mechanisms. All these processes flow into a series of common pathways of cellular
      activation. Knowledge of these mechanisms could serve to identify which patients
      would benefit from a specific treatment before applying therapies that act
      indiscriminately in the inflammatory response.

PMID- 16949002
TI  - [The CRUSADE study, evaluation model of quality in percutaneous coronary
      intervention].
AB  - Improvement of care quality does not end with the publication of clinical trials
      that show clinical evidence of effectiveness or with its support by the different
      international therapeutic guides. This quality improvement requires evaluation in
      the real population. This can be done by analysis of clinical registries, that
      would evaluate adequate compliance of the clinical guides and their effectiveness
      in the real population. The CRUSADE study is a study that evaluates use,
      prognosis and factors of prediction, of invasive strategy by early percutaneous
      coronary intervention (PCI) (first 48 hours of the ischemic event) in high-risk
      patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS). Of the
      17,926 patients studied, 8037 (44.8%) underwent cardiac catheterism in the first
      48 hours of the ischemic event. Intrahospital mortality of the invasive strategy
      was significantly less than medical treatment (2.5% versus 3.7%). The patients
      who underwent an early invasive strategy were a selected population, as the more
      solid independent prediction factors were associated to early invasive treatment:
      cardiology care, earlier age, absence of renal failure, absence of heart failure
      both previously or on arrival to the hospital and lower heart rate. Finally, it
      could be concluded that, in spite of the decrease of mortality achieved with the
      early invasive strategy, this would not done in most of the patients, being
      reserved for subgroups with lower comorbidity and for those seen by the
      cardiologists.

PMID- 16949003
TI  - [Critical patients carriers of pacemakers and automatic defibrillators].
AB  - Pacemakers and automatic defibrillators are being increasingly implanted and thus
      more patients with these devices are being admitted to our Services. We should
      recognize these patients and be capable of understanding the functioning of the
      apparatus implanted. Scheduled when the patient was in a stable situation, its
      scheduling may not be sufficient in a pathological situation with increase of
      metabolic demands. It may even contribute to worsening the clinical picture that
      our patient has. Sufficient knowledge should allow us to recognize this problem
      and even to propose changes in the programming as part of the patient's
      treatment. Correct clinical management of these patients requires greater
      involvement in the understanding of these devices in our daily tasks.

PMID- 16949004
TI  - [Adverse events in Intensive Medicine. Managing risk].
AB  - Health care interventions entail a risk of adverse events (AE), that may cause
      lesions, incapacities and even death in the patients. Given the complexity of the
      care of the critical patient, the Critical Care Services are a high risk setting
      for the appearance of AE in these patients, many of them avoidable. Several
      studies show the influence of organizational factors focused on the system in the
      reduction of care risk and on the result of the critical patients. The voluntary
      and anonymous registry and reporting systems make it possible to identify a
      significant percentage of these incidents, analyze the factors related (that
      contribute or limit), establish preventive strategies, permitting management of
      risk, and potentially reduce the appearance and consequences of avoidable AE with
      all this. Initiatives such as the ICU Safety Reporting System (ICUSRS), that use
      a web database as registry system and includes contributions from different
      sites, favor the safety and risk culture, essential in the improvement of health
      quality of critical patients.

PMID- 16949005
TI  - [Use of methylene blue in the treatment of vasoplegic syndrome of post-operative
      heart surgery].
AB  - Vasoplegia is a frequent complication in post-operative heart surgery and
      determines a significant increase in morbidity-mortality. When vasoplegia
      persists in spite of optimized fluid therapy with the use of Swan-Ganz catheter,
      we have a safe, effective and economical alternative, methylene blue. We present
      the case of a patient who developed vasoplegia refractory to treatment and shock
      in the scheduled post-operative period of myocardial revascularization. The use
      of a single dose of methylene blue resolved the hemodynamic instability and
      allowed for total discontinuation of vasoactive drugs. Thus, we present this new
      indication of methylene blue, still not approved by the corresponding bodies, for
      which no national publications have been found and its clinical management and
      the absence of adverse effects after its use.

PMID- 16949006
TI  - [Acute mediastinic tamponade and massive bilateral pleural effusion after central
      venous catheterization].

PMID- 16949007
TI  - [Cerebellar hemorrhaging after excision of a pituitary tumor by supratentorial
      craniotomy].

PMID- 16949008
TI  - [Stunned myocardium in brain death].

PMID- 16949009
TI  - [Images in intensive medicine].

PMID- 16949011
TI  - [Secondary prevention of coronary heart disease and gender perspective in two
      primary healthcare centers].
AB  - BACKGROUND AND OBJECTIVE: Our goal was to describe the secondary prevention of
      coronary heart disease activities in two primary healthcare centers and to
      analyze differences according to gender. PATIENTS AND METHOD: Retrospective
      follow-up study (medical records audit) during one year of 187 patients
      discharged after one myocardial infarction to identify the use of preventive
      advice and treatments. RESULTS: Men had more exercise (66.7%), smoking (62.9%)
      and alcohol advice (20.0%) and less diet advice (62.9%) than women (34.3%, 2.9%,
      0.0%, 94.3%, respectively). After one year of follow-up, there were no
      differences in antiplatelet therapy (99.3%), betablockers (41.4%) and statins
      (70.7%), yet the use of drugs with action on the renin-angiotensin system showed
      notable differences (men: 50.5%; women: 5.7%; P < .05). Overall, 66.6% of the men
      vs. 31.4 of the women received three or more treatments. There were no
      differences among health centers. CONCLUSIONS: Although secondary prevention
      seems to have improved along time, some problems remain, especially in women.

PMID- 16949010
TI  - [Prognosis of patients admitted in a coronary care unit after resucitating from
      out-of-hospital sudden cardiac death].
AB  - BACKGROUND AND OBJECTIVE: The aims of the present study were to analyze the
      prognosis after resuscitation from out-of-hospital sudden cardiac death in
      patients admitted to the coronary care unit, and to identify the predictor
      variables of morbi-mortality. PATIENTS AND METHOD: From November 1999 to January
      2004 we analyzed 63 patients (47 males) aged 61 +/- 12 years who were admitted to
      the coronary care unit following successful resuscitation from sudden cardiac
      death. The clinical and electrocardiographic characteristics were correlated with
      the mortality and neurological impairment. RESULTS: Thirty-five patients (55.5%)
      were discharged, while twenty-eight patients (45.5%) died 28 +/- 4 days after
      admission, most of them during hospitalization. The main underlying disorder was
      coronary artery disease (80.9%). When survivors and non-survivors were compared,
      the variables associated with a worse prognosis were diabetes mellitus (68.4% vs
      17.1%, P < .02), the presence of valvular heart disease (28.6% vs 0%, p < 0.003),
      chronic atrial fibrillation (42.9% vs 14.3%, P < .02) and asystole as the initial
      rhythm observed (42.9% vs 11.4%, P < .01). Multivariate analysis identified
      asystole as an independent factor of poor prognosis (P < .02). Death was due to
      severe postanoxic neurological damage in 23 of 28 deaths (82.1%). The remaining 5
      patients died due to their underlying cardiac disease (P < .01). The variables
      associated with neurological damage were out-of hospital resuscitation, delay in
      beginning resuscitation maneuvers, arrival time > 5 minutes and unconsciousness
      on admission. CONCLUSIONS: Although many patients survive following resuscitation
      from out-of-hospital sudden cardiac death, mortality remains high. Neurological
      impairment is the main cause of mortality. Prognosis is determined by the
      variables related to the underlying disease, the delay in onset of resuscitation
      maneuvers and postanoxia cerebral damage.

PMID- 16949012
TI  - [Arterial mean pressure and pulse pressure in young hypertensive patients].
AB  - BACKGROUND AND OBJECTIVE: Evidence shows that pulse pressure (PP) is very useful
      when assessing the hypertensive patient and this has led to a lower use of mean
      arterial pressure (MAP). We intended to demonstrate that MAP should be better
      than PP in young hypertensive patients. SUBJECTS AND METHOD: Cross-sectional
      study in 70 white males with ages among 16-40 years, distributed in two groups of
      35 individuals labelled as control group or hypertensive patients, who were
      assessed by echocardiography. RESULTS: PP was similar (36.37 +/- 7.90 mmHg vs.
      36.67 +/- 9.41 mmHg, p = 0.8851) in both control and hypertensive groups, as well
      as the arterial compliance (2.22 +/- 0.62 ml/mmHg vs. 2.41 +/- 0.77 ml/mmHg, p =
      .2555) and the aortic stiffness index (0.88 +/- 0.23 vs. 0.91 +/- 0.33, P =
      .6591). MAP (94.85 +/- 8.68 mmHg vs. 115.11 +/- 10.01 mmHg, P < .001) and total
      peripheral resistance index (TPRI) [2681.42 +/- 602.31 dinas.s.cm-5/m2 vs.
      3120.68 +/- 741.74 dinas.s.cm-5/m2, p = .0066] were higher in hypertensive
      patients. CONCLUSIONS: In our cross-sectional assessment in young hypertensive
      patients, MAP and its determiner (TPRI) were modified, with no important changes
      in the PP or its determiners.

PMID- 16949013
TI  - [Prevention of immunologic rejection in human embryonic stem cell
      transplantation].

PMID- 16949014
TI  - [Objectives and methods of assessment of professional competence: around the
      Miller's pyramid].

PMID- 16949015
TI  - [Non pharmacologic and alternative treatments in fibromyalgia].

PMID- 16949016
TI  - [New approaches in obesity treatment: the gastrointestinal tract as an endocrine
      organ].
AB  - The gastrointestinal tract, besides digesting and processing nutrients, is now
      regarded as an endocrine organ able to modulate appetite, satiety, and
      carbohydrate metabolism. Several enteroendocrine cells produce numerous peptides
      codifying either orexigenic (ghrelin, orexins) or anorexigenic signals
      (pancreatic polypeptide, peptide YY, cholecystokinin, amylin, bombesin homologs,
      apolipoprotein A-IV, glucose-dependent insulinotropic polypeptide, glucagon-like
      peptide 1, oxyntomodulin), which interact in a complex network with other
      peripheral signals of energy balance and with different neuropeptides involved in
      the central control of appetite and energy homeostasis. The growing knowledge of
      the actions of these gastrointestinal peptides on appetite regulation and
      carbohydrate metabolism, and subsequent synthesis of analogs, particularly those
      derived from amylin and incretins, herald a new era in the therapy of 2 closely
      related diseases, obesity and type 2 diabetes mellitus.

PMID- 16949017
TI  - [A 49 years old woman with a cardiac mass].

PMID- 16949018
TI  - [Electroconvulsive therapy in patients with high medical complexity].

PMID- 16949019
TI  - [Lipid profile analysis in patients with early rheumatoid arthritis].

PMID- 16949020
TI  - [Comparison of the Score and Framingham-DORICA models to estimate the
      cardiovascular risk in a cohort of hypertensive patients from southern Spain].

PMID- 16949021
TI  - [Pegylated interferon treatment and severe thrombocytopenia].

PMID- 16949022
TI  - [Psoriasis induced by infliximab: a paradoxical event].

PMID- 16949023
TI  - [Atrio-ventricular block in Prinzmetal's angina refractary to medical treatment].

PMID- 16949024
TI  - [Severe hypoglycemia after somatostatin in a diabetic patient with
      gastrointestinal fistula treated with total parenteral nutrition].

PMID- 16949025
TI  - [Spontaneous rupture of the spleen: a rare form of onset gastric carcinoma].

PMID- 16949026
TI  - [Do statins have benefit on migraine].

PMID- 16949027
TI  - Further notes on the application of zero-inflated models in highway safety.
AB  - The intent of this note is to succinctly articulate additional points that were
      not provided in the original paper (Lord et al., 2005) and to help clarify a
      collective reluctance to adopt zero-inflated (ZI) models for modeling highway
      safety data. A dialogue on this important issue, just one of many important
      safety modeling issues, is healthy discourse on the path towards improved safety
      modeling. This note first provides a summary of prior findings and conclusions of
      the original paper. It then presents two critical and relevant issues: the
      maximizing statistical fit fallacy and logic problems with the ZI model in
      highway safety modeling. Finally, we provide brief conclusions.

PMID- 16949028
TI  - [Advanced ovarian cancer, an optimal surgical treatment is possible to all
      patients owing to laparoscopy].

PMID- 16949029
TI  - The membrane-induced structure of melittin is correlated with the fluidity of the
      lipids.
AB  - The effect of the bee toxin melittin on DMPC dynamics in fast-tumbling bicelles
      has been investigated. The (13)C R(1) and (13)C-(1)H NOE relaxation parameters
      for DMPC were used to monitor the effect of melittin and cholesterol on lipid
      dynamics. It was found that melittin has the largest effect on the DMPC mobility
      in DMPC/DHPC bicelles, while less effect was observed in cholesterol-doped
      bicelles, or in bicelles made with CHAPS, indicating that the rigidity of the
      membrane affects the melittin-membrane interaction. CD spectra were analysed in
      terms of cooperativity of the alpha-helix to random coil transition in melittin,
      and these results also indicated similar differences between the bicelles. The
      study shows that bicelles can be used to investigate lipid dynamics by spin
      relaxation, and in particular of peptide-induced changes in membrane fluidity.

PMID- 16949030
TI  - A test of the interactive effects of anxiety sensitivity and mindfulness in the
      prediction of anxious arousal, agoraphobic cognitions, and body vigilance.
AB  - The present investigation sought to examine the interactive effects of anxiety
      sensitivity [AS; Reiss, S., & McNally, R. J. (1985). Expectancy model of fear. In
      S. Reiss, & R. R. Bootzin (Eds.), Theoretical issues in behavior therapy (pp. 107
      121). San Diego: Academic Press] and mindfulness [Brown, K. W., & Ryan, R. M.
      (2003). The benefit of being present: Mindfulness and its role in psychological
      well-being. Journal of Personality and Social Psychology, 84, 822-848] in
      predicting panic-relevant processes. A community sample of 248 individuals
      participated in the study by completing a battery of self-report instruments.
      Consistent with prediction, the interaction between AS and mindfulness
      significantly predicted anxious arousal symptoms and agoraphobic cognitions,
      above and beyond the individual main effects, and did not significantly predict
      anhedonic depression symptoms. Contrary to prediction, the AS by mindfulness
      interaction did not significantly predict body vigilance. Theoretical
      implications are discussed and future directions are delineated.

PMID- 16949031
TI  - n-Butyrate inhibits Jun NH(2)-terminal kinase activation and cytokine
      transcription in mast cells.
AB  - Mast cells are well known to contribute to type I allergic conditions but only
      recently have been brought in association with chronic relapsing/remitting
      autoimmune diseases such as celiac disease and ulcerative colitis. Since the
      bacterial metabolite n-butyrate is considered to counteract intestinal
      inflammation we investigated the effects of this short chain fatty acid on mast
      cell activation. Using RNAse protection assays and reporter gene technology we
      show that n-butyrate downregulates TNF-alpha transcription. This correlates with
      an impaired activation of the Jun NH(2)-terminal kinase (JNK) but not other MAP
      kinases such as ERK and p38 that are largely unaffected by n-butyrate. As a
      consequence, we observed a decreased nuclear activity of AP-1 and NF-AT
      transcription factors. These results indicate that n-butyrate inhibits critical
      inflammatory mediators in mast cells by relatively selectively targeting the JNK
      signalling.

PMID- 16949032
TI  - Social stress increases biopyrrins, oxidative metabolites of bilirubin, in mouse
      urine.
AB  - We investigated whether or not three kinds of social stress (isolation, crowding,
      and confrontation) increase urinary excretion of biopyrrins, oxidative
      metabolites of bilirubin, in mice. Male BALB/c mice (4 weeks old) were housed 5
      per cage for 10 days. After acclimatization, mice were exposed to the above
      mentioned three kinds of psychosocial stress. Mouse blood and urine samples were
      collected after 2, 7, and 30 days of stress. Serum levels of corticosterone and
      urinary levels of biopyrrins were determined by EIA and ELISA, respectively.
      Adrenal hypertrophy, significant increases in serum concentration of
      corticosterone and in urinary excretion of biopyrrins were observed in mice
      exposed to these types of social stress for 7 days. These levels decreased after
      30 days, though they were still rather high compared to the control group. These
      results suggested that social stress causes oxidative stress and that biopyrrins
      could be useful biomarkers of psychosocial stress.

PMID- 16949033
TI  - Comparison of susceptibility and transcription profile of the new antifungal
      hassallidin A with caspofungin.
AB  - This is the first report on the antifungal effects of the new glycolipopeptide
      hassallidin A. Due to related molecular structure moieties between hassallidin A
      and the established antifungal drug caspofungin we assumed parallels in the
      effects on cell viability. Therefore we compared hassallidin A with caspofungin
      by antifungal susceptibility testing and by analysing the genome-wide
      transcriptional profile of Candida albicans. Furthermore, we examined
      modifications in ultracellular structure due to hassallidin A treatment by
      electron microscopy. Hassallidin A was found to be fungicidal against all tested
      Candida species and Cryptococcus neoformans isolates. MICs ranged from 4 to 8
      microg/ml, independently from the species. Electron microscopy revealed
      noticeable ultrastructural changes in C. albicans cells exposed to hassallidin A.
      Comparing the transcriptional profile of C. albicans cells treated with
      hassallidin A to that of cells exposed to caspofungin, only 20 genes were found
      to be similarly up- or down-regulated in both assays, while 227 genes were up- or
      down-regulated induced by hassallidin A specifically. Genes up-regulated in cells
      exposed to hassallidin A included metabolic and mitotic genes, while genes
      involved in DNA repair, vesicle docking, and membrane fusion were down-regulated.
      In summary, our data suggest that, although hassallidin A and caspofungin have
      similar structures, however, the effects on susceptibility and transcriptional
      response to yeasts seem to be different.

PMID- 16949034
TI  - Differential effect of celecoxib on tissue factor expression in human endothelial
      and vascular smooth muscle cells.
AB  - In endothelial cells (EC), celecoxib inhibits expression of tissue factor (TF), a
      key protein for initiation and propagation of thrombus formation. The current
      study was designed to examine the effect of celecoxib on TF expression and
      activity in VSMC. In contrast to EC, celecoxib increased TNF-alpha-induced TF
      expression and surface activity in VSMC by 33% and 20%, respectively, as compared
      to TNF-alpha alone, while rofecoxib or NS-398 had no effect. Celecoxib increased
      p38 MAP kinase (p38), p44/42 MAP kinase (ERK), and p70S6 kinase (p70S6K)
      phosphorylation while leaving JNK activation unaffected. Simultaneous inhibition
      of p38 and ERK reduced TNF-alpha-induced TF expression by 59%, while inhibition
      of JNK with SP600125 did not affect TF expression. Thus, in contrast to
      endothelial cells, celecoxib does not inhibit TF expression in VSMC, but instead
      enhances it. As neither rofecoxib nor NS-398 affected TF expression, this effect
      does not seem to be related to COX-2 inhibition but rather appears to be mediated
      by an increase in p38, ERK, and p70S6K activation. The observation that the
      inhibiting effect of celecoxib on endothelial TF expression does not extend to
      VSMC may have important implications for patients with cardiovascular disease.

PMID- 16949035
TI  - Identification and expression of alternative splice variants of the mouse Ppp1r3b
      gene in lung epithelial cells.
AB  - Hepatic glycogen-targeting subunit GL of protein phosphatase-1 (PP1), which is
      encoded by the gene Ppp1r3b, is one of a family of proteins that target PP1 to
      glycogen and regulate its activity on enzymes of glycogen metabolism. GL is
      primarily expressed in the liver where it promotes hepatic glycogen synthesis in
      response to insulin. Here, we show that GL is highly expressed in embryonic mouse
      lungs. GL utilizes two alternative promoters and 5' non-coding exons, which
      produce at least three alternatively spliced transcripts that encode identical
      proteins. Expression of GL in the lung is detectable as early as embryonic day
      (E) 12.5 and increases by E16.5, however, it declines before birth. In situ
      hybridization of mouse embryonic lung revealed that GL is expressed in bronchial
      epithelial cells. Thus, the temporal and spatial expression of GL in the lung
      suggests that it has a potential role in glycogen metabolism during lung
      development.

PMID- 16949036
TI  - Identification of P2X4 receptor-specific residues contributing to the ivermectin
      effects on channel deactivation.
AB  - Ivermectin (IVM) applied extracellularly increases the sensitivity of P2X4
      receptor (P2X4R) to ATP, enhances the maximum current amplitudes, and greatly
      prolongs the deactivation kinetics. In this manuscript, we focused on
      identification of receptor-specific residues responsible for IVM effects on
      channel gating using the wild-type rat homomeric P2X4R, several chimeric
      P2X2/P2X4 receptors, and single-point P2X4R-specific mutants in the ectodomain
      and two transmembrane domains. Experiments with chimeric receptors revealed that
      the Val49-Val61 but not the Val64-Tyr315 ectodomain sequence is important for the
      effects of IVM on channel deactivation. Receptor-specific mutations placed in the
      Gly29-Val61 and Asp338-Leu358 regions showed the importance of Trp50, Val60, and
      Val357 residues in IVM regulation of the rate of channel deactivation, but not on
      the maximum current amplitude. These results suggest that the transmembrane
      domains and the nearby ectodomain region contribute to the effects of IVM on
      channel deactivation.

PMID- 16949038
TI  - Obstructive hypertrophic cardiomyopathy is associated with reduced expression of
      vinculin in the intercalated disc.
AB  - Mutations in the cardiac-specific insert of vinculin, metavinculin, rarely cause
      hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Subsequently,
      a missense mutation in the ubiquitously expressed vinculin was discovered in a
      patient with obstructive HCM. Microscopic examination of both myectomy specimens
      from patients bearing genetic defects in metavinculin and vinculin showed a
      marked reduction of vinculin/metavinculin expression in the intercalated disc,
      but normal expression in the Z-disc. Given that distinct functional domains were
      altered by the metavinculin and vinculin mutations, we hypothesized that the
      intercalated disc-specific reduction of vinculin may stem from left ventricular
      tract obstruction in general rather than rarely observed perturbations in VCL
      encoded vinculin. To test this hypothesis, we examined the localization of
      vinculin/metavinculin in hypertrophied human heart tissue from patients with
      cardiovascular conditions associated with obstruction and hemodynamic overload
      using an immunohistochemistry approach. Tissue specimens derived from patients
      with obstructive HCM and aortic stenosis (AS) showed a universal defect of
      vinculin/metavinculin expression in the intercalated disc but preserved
      expression in the cardiac Z-disc, whereas tissue specimens derived from patients
      with either DCM, hypertensive heart disease (HTN), or pulmonary hypertension
      (PHTN) exhibited normal expression of vinculin/metavinculin in both the Z- and
      the intercalated disc despite being associated with hypertrophy. Results of this
      study suggest that cardiac hypertrophy may be associated with different
      expression of the marker vinculin/metavinculin depending on the underlying
      pathophysiology; hemodynamic overload may not affect the localization whereas
      obstructive disease substantially reduces the expression of vinculin
      preferentially in the intercalated disc.

PMID- 16949037
TI  - Inhibition of PrPSc formation by synthetic O-sulfated glycopyranosides and their
      polymers.
AB  - Sulfated glycosaminoglycans (GAGs) and sulfated glycans inhibit formation of the
      abnormal isoform of prion protein (PrPSc) in prion-infected cells and prolong the
      incubation time of scrapie-infected animals. Sulfation of GAGs is not tightly
      regulated and possible sites of sulfation are randomly modified, which
      complicates elucidation of the fundamental structures of GAGs that mediate the
      inhibition of PrPSc formation. To address the structure-activity relationship of
      GAGs in the inhibition of PrPSc formation, we screened the ability of various
      regioselectively O-sulfated glycopyranosides to inhibit PrPSc formation in prion
      infected cells. Among the glycopyranosides and their polymers examined, monomeric
      4-sulfo-N-acetyl-glucosamine (4SGN), and two glycopolymers, poly-4SGN and poly-6
      sulfo-N-acetyl-glucosamine (poly-6SGN), inhibited PrPSc formation with 50%
      effective doses below 20 microg/ml, and their inhibitory effect became more
      evident with consecutive treatments. Structural comparisons suggested that a
      combination of an N-acetyl group at C-2 and an O-sulfate group at either O-4 or O
      6 on glucopyranoside might be involved in the inhibition of PrPSc formation.
      Furthermore, polymeric but not monomeric 6SGN inhibited PrPSc formation,
      suggesting the importance of a polyvalent configuration in its effect. These
      results indicate that the synthetic sulfated glycosides are useful not only for
      the analysis of structure-activity relationship of GAGs but also for the
      development of therapeutics for prion diseases.

PMID- 16949039
TI  - Mechanism of anaerobic degradation of triethanolamine by a homoacetogenic
      bacterium.
AB  - Triethanolamine (TEA) is converted into acetate and ammonia by a strictly
      anaerobic, gram-positive Acetobacterium strain LuTria3. Fermentation experiments
      with resting cell suspensions and specifically deuterated substrates indicate
      that in the acetate molecule the carboxylate and the methyl groups correspond to
      the alcoholic function and to its adjacent methylene group, respectively, of the
      2-hydroxyethyl unit of TEA. A 1,2 shift of a hydrogen (deuterium) atom from -CH2
      O- to =N-CH2- without exchange with the medium was observed. This fact gives
      evidence that a radical mechanism occurs involving the enzyme and/or coenzyme
      molecule as a hydrogen carrier. Such a biodegradation appears analogous to the
      conversion of 2-phenoxyethanol into acetate mediated by another strain of the
      anaerobic homoacetogenic bacterium Acetobacterium.

PMID- 16949040
TI  - Overexpression of human WNK1 increases paracellular chloride permeability and
      phosphorylation of claudin-4 in MDCKII cells.
AB  - Pseudohypoaldosteronism type II (PHAII), an autosomal dominant disorder
      characterized by hypertension, hyperkalemia, and hyperchloremic acidosis, is
      reportedly due to mutations in WNK1 and WNK4 kinase genes. However, the
      pathogenesis of the disease remains unknown. Mutations in the WNK1 gene are the
      deletions in the first intron, which reportedly increases WNK1 mRNA expression.
      Thus, we generated WNK1 over-expressing stable cell lines using MDCKII cells to
      model the distal nephron of PHAII patients. Using these cell lines, we
      investigated whether increased WNK1 expression might affect paracellular chloride
      permeability and claudin phosphorylation, since we previously observed an
      increase in both with a disease-causing mutant WNK4. WNK1 expression in MDCKII
      cells increased chloride permeability two to threefold. Co-expression of wild
      type WNK4 did not further increase WNK1-enhanced chloride permeability. WNK1
      expression also induced phosphorylation of endogenous claudin-4 in MDCKII cells,
      as well as over-expressed claudin-4. Combined, these results suggest that
      increased WNK1 expression has the same effect on chloride permeability and
      claudin phosphorylation as the mutant WNK4. Thus, increased chloride shunt may be
      involved in the pathogenesis of PHAII caused by WNK1 mutations.

PMID- 16949041
TI  - Adenovirus-mediated transfer of siRNA against Runx2/Cbfa1 inhibits the formation
      of heterotopic ossification in animal model.
AB  - The heterotopic ossification of muscles, tendons, and ligaments is a common
      problem faced by orthopaedic surgeons. Runx2/Cbfa1 plays an essential role during
      the osteoblast differentiation and is considered as a molecular switch in
      osteoblast biology. RNA interference technology is a powerful tool for silencing
      endogenous or exogenous genes in mammalian cells. In this study, we investigated
      the effect of Runx2/Cbfa1-specific siRNA on osteoblast differentiation and
      mineralization in osteoblastic cells, and then constructed adenovirus containing
      siRNA against Runx2/Cbfa1 (Ad-Runx2-siRNA) to inhibit the formation of
      heterotopic ossification induced by BMP4, demineralized bone matrix, and trauma
      in animal model. Our results showed that the Runx2/Cbfa1-specific siRNA could
      inhibit the expression of Runx2/Cbfa1 at the level of mRNA and protein. Analysis
      of the expression of osteoblast maturation genes including type I collagen,
      osteopontin, bone sialoprotein, and osteocalcin, alkaline phosphatase activity,
      and matrix mineralization (von kossa) revealed that osteoblast differentiation
      was inhibited in cultured primary mouse osteoblasts transduced with Ad-Runx2
      siRNA. Furthermore, adenovirus-mediated transfer of siRNA against Runx2/Cbfa1
      could inhibit the formation of heterotopic ossification induced by BMP4,
      demineralized bone matrix, and trauma in animal model. It is likely that the
      inhibition of Runx2/Cbfa1 by RNAi could be developed as a powerful approach to
      prevent or treat heterotopic ossification.

PMID- 16949042
TI  - Patients with inflammatory arthritic diseases harbor elevated serum and synovial
      fluid levels of free and immune-complexed glucose-6-phosphate isomerase (G6PI).
AB  - In K/BxN mice, anti-glucose-6-phosphate isomerase (G6PI) IgG antibodies (Abs)
      cause joint-specific inflammation and destruction. Anti-G6PI Abs are also present
      in humans with inflammatory arthritis, especially among patients with rheumatoid
      arthritis (RA). A contributing factor to the induction of such autoantibodies may
      be upregulated expression of the corresponding antigen G6PI in affected tissues
      and/or increased levels of G6PI in the circulation. To determine G6PI levels and
      the presence of free G6PI and/or G6PI-containing immune complexes in sera and
      synovial fluids (SF) of patients with different arthritides, serum and SF
      obtained concomitantly from 91 clinically well-defined arthritis patients were
      assessed in a blinded manner for G6PI enzymatic assay and for G6PI protein
      concentration by ELISA. Sera and SF from patients with immune-based inflammatory
      arthritis contained significantly higher levels of G6PI enzymatic activity
      compared to sera or SF from patients with non-immune-based inflammatory arthritis
      or healthy controls. In addition, significantly higher levels of total G6PI
      protein concentration (including both enzymatically active and inactive forms)
      were present in sera of RA patients vs. those with other immune-based or non
      immune-based inflammatory arthritis.G6PI in sera and SF were present both as G6PI
      containing immune complexes and as free G6PI, with the majority of free G6PI
      existing as tetramers with lesser amounts of dimers and monomers. Levels of G6PI
      enzymatic activity in the sera of most immune-based inflammatory arthritis
      patients are elevated and may reflect ongoing inflammation and cell destruction.
      The high serum levels of enzymatically inactive forms of G6PI in RA relative to
      those in other arthritic diseases are partially due to G6PI-containing immune
      complexes, a portion of which also contains C1q. Overall, our study supports the
      notion that elevated G6PI levels present in patients with immune-based
      inflammatory arthritis may contribute to elevated levels of anti-G6PI Abs and
      G6PI/anti-G6PI immune complexes. This, in turn, may trigger production of
      proinflammatory cytokines and perpetuate the inflammatory process.

PMID- 16949043
TI  - Secondary structure formations of conotoxin genes: a possible role in mediating
      variability.
AB  - Small venomous peptides called conotoxins produced by the predatory marine snail
      (genus Conus) present an interesting case for mutational studies. They have a
      high degree of amino acid variability among them yet they possess highly
      conserved structural elements that are defined by cysteine residues forming
      disulfide bridges along the length of the mature peptide. It has been observed
      that codons specifying these cysteines are also highly conserved. It is unknown
      how such codon conservation is maintained within the mature conotoxin gene since
      this entire region undergoes an accelerated rate of mutation. There is evidence
      suggesting that nucleic acids wield some influence in mechanisms that dictate the
      region and frequency where mutations occur in DNA. Nucleic acids exert this
      effect primarily through secondary structures that bring about local peaks and
      troughs in the energy relief of these transient formations. Secondary structure
      predictions of several conotoxin genes were analyzed to see if there was any
      correspondence between the highly variable regions of the conotoxin. Regions of
      the DNA encompassing the conserved Cys codons (and several other conserved amino
      acid codons) have been found to correspond to predicted secondary structures of
      higher stabilities. In stark contrast the regions of the conotoxin that have a
      higher degree of variation correlate to regions of lower stability. This striking
      co-relation allows for a simple model of inaccessibility of a mutator to these
      highly conserved regions of the conotoxin gene allowing them a relative degree of
      resistance towards change.

PMID- 16949044
TI  - Characterization of oxidation end product of plasma albumin 'in vivo'.
AB  - Anti-oxidants are paradoxically much lower in plasma than inside cells even blood
      is comparably exposed to the oxidative stress. 'In vitro' models suggest a
      critical role of albumin as substitutive anti-oxidant in plasma but no proof for
      this role is available 'in vivo.' Herein, we demonstrate by LC/MS/MS that plasma
      albumin undergoes massive oxidation in primary nephrotic syndrome, involving
      stable sulphonation SO3- of the free SH of Cys 34 with +48Da increase in exact
      mass of the protein (ESI-MS) and formation of a fast moving isoform in the pH
      range between 5 and 7. Physical-chemical experiments with DSC and fluorescence
      spectra indicate a thermal stabilization of the structure upon oxidation. This is
      the first demonstration of massive oxidation of albumin 'in vivo' that reflects a
      functional role of the protein. Free radicals should be implicated in the
      pathogenesis of proteinuria in human FSGS.

PMID- 16949045
TI  - Quantitative methylation-sensitive arbitrarily primed PCR method to determine
      differential genomic DNA methylation in Down Syndrome.
AB  - Relative levels of DNA hypermethylation were quantified in DS individuals using a
      new method based on a combination of methylation-sensitive arbitrarily primed
      polymerase chain reaction (MS-AP-PCR) and quantification of DNA fragments with
      the Agilent 2100 bioanalyzer. Four of the DS individuals had low plasma total
      homocysteine (tHcy) level (4.3 +/- 0.3 micromol/l) and 4 other had high-tHcy
      level (14.1 +/- 0.9 micromol/l). Eight healthy control individuals were matched
      to the DS cases for age, sex, and tHcy levels. We have identified and quantified
      six hypermethylated fragments. Their sizes ranged from 230-bp to 700-bp. In cases
      and controls, low-tHcy did not affect methylation level of identified fragments,
      mean methylation values were 68.0 +/- 39.7% and 52.1 +/- 40.3%, respectively. DNA
      methylation in DS individuals did not change significantly (59.7+/-34.5%) in
      response to high-tHcy level in contrast to controls (23.4 +/- 17.7%, P = 0.02).
      Further, the quantitative MS-AP-PCR using this microfludic system is a useful
      method for determining differential genomic DNA methylation.

PMID- 16949046
TI  - Inhibition of the anti-adipogenic Hedgehog signaling pathway by cyclopamine does
      not trigger adipocyte differentiation.
AB  - Dysregulation of Hedgehog signaling can lead to several pathologies such as
      congenital defects and cancer. Here, we show that Hedgehog signaling is active in
      undifferentiated 3T3-L1 cells and decreases during adipocyte differentiation.
      Interestingly, this is paralleled by a decrease in Indian Hedgehog expression. We
      then tested if this down-regulation was sufficient to induce adipocyte
      differentiation. To this end, we demonstrate that the well-characterized Hedgehog
      inhibitor cyclopamine induced a decrease in Hedgehog signaling, similar to the
      one observed during adipocyte differentiation. However, cyclopamine did not
      induce nor potentiate adipocyte differentiation, as monitored by triglyceride
      staining and by the expression of several adipocyte markers: aP2, adipsin,
      C/EBPalpha, and Pref-1. Moreover, cyclopamine cannot substitute for other
      components of the differentiation medium: insulin, dexamethasone or IBMX. These
      results indicate that although Hedgehog signaling decreases during adipocyte
      differentiation, this down-regulation is not sufficient to trigger adipocyte
      differentiation. This suggests that Hedgehog signaling is an inadequate
      pharmacological target for patient suffering from syndromes associated with a
      decrease in fat mass, such as the ones observed in lipodystrophies.

PMID- 16949047
TI  - Involvement of Sp1 in lipopolysaccharide-induced expression of HDC mRNA in RAW
      264 cells.
AB  - The involvement of Sp1 in the lipopolysaccharide (LPS)-induced transcription of
      HDC mRNA in the mouse macrophage-like cell line RAW 264 was analyzed. LPS
      increased the levels of HDC mRNA 4 h after the stimulation in a concentration
      dependent manner. Mithramycin A, an inhibitor of the binding of the Sp family to
      the GC box, reduced the LPS-induced increase in the levels of HDC mRNA at 4 h and
      HDC protein at 8 h in a concentration-dependent manner. By conducting
      electrophoretic mobility shift assays, we found that one of the transcription
      factors binding to the DNA probe containing the GC box sequence of the mouse HDC
      gene promoter region was Sp1, and that levels of Sp1-DNA probe complexes were
      increased by stimulation with LPS although the protein levels of Sp1 were not
      changed. These results suggested that Sp1 is one of the transcription factors
      that regulate the LPS-induced expression of HDC in RAW 264 cells.

PMID- 16949048
TI  - Identification of BRCA1 and BRCA2 mutations from Korean breast cancer patients
      using denaturing HPLC.
AB  - In order to investigate the presence and function of BRCA mutations in Korean
      breast cancer patients, mutational analyses using denaturing HPLC (DHPLC) were
      performed for 1020 breast cancer patients and 167 normal females. We identified
      14 deleterious mutations that included 10 frameshift mutations and 4 nonsense
      mutations. Among these 14 mutations, we found 3 novel BRCA1 and 3 novel BRCA2
      mutations. We found that BRCA deleterious mutations were present in 19 of the
      1020 patients (1.8%). Three of the 14 deleterious mutations were detected in 7 of
      these 19 patients. The three mutations were also identified in other studies for
      BRCA mutations in the Korean population, suggesting that they are possible
      founder mutations of BRCA for the Korean population. We plan to provide
      fundamental data for larger population-based studies to establish the frequency
      and significance of BRCA mutations in Korean breast cancer patients.

PMID- 16949049
TI  - AMPK regulation of the growth of cultured human keratinocytes.
AB  - AMP kinase (AMPK) is a fuel sensing enzyme that responds to cellular energy
      depletion by increasing processes that generate ATP and inhibiting others that
      require ATP but are not acutely necessary for survival. In the present study, we
      examined the relationship between AMPK activation and the growth (proliferation)
      of cultured human keratinocytes and assessed whether the inhibition of
      keratinocyte growth by vitamin D involves AMPK activation. In addition, we
      explored whether the inhibition of keratinocyte proliferation as they approach
      confluence could be AMPK-related. Keratinocytes were incubated for 12 h with the
      AMPK activator, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
      At concentrations of 10(-4) and 10(-3) M, AICAR inhibited keratinocyte growth by
      50% and 95%, respectively, based on measurements of thymidine incorporation into
      DNA. It also increased AMPK and acetyl CoA carboxylase phosphorylation (P-AMPK
      and P-ACC) and decreased the concentration of malonyl CoA confirming that AMPK
      activation had occurred. Incubation with the thiazolidinedione, troglitazone (10(
      6) M) caused similar alterations in P-AMPK, P-ACC, and cell growth. In contrast,
      the well known inhibition of keratinocyte growth by 1,25-dihydroxyvitamin D3 (10(
      7) and 10(-6) M) was not associated with changes in P-AMPK or P-ACC. Like most
      cells, the growth of keratinocytes diminished as they approached confluence.
      Thus, it was of note that we found a progressive increase in P-AMPK (1.5- to 2
      fold, p < 0.05) as keratinocytes grown in control medium went from 25% to 100%
      confluence. In conclusion, the data are consistent with the hypothesis that
      activation of AMPK acts as a signal to diminish the proliferation of cultured
      keratinocytes as they approach confluence. They also suggest that AMPK
      activators, such as AICAR and troglitazone, inhibit keratinocyte growth and that
      the inhibition of cell growth by 1,25-dihydroxyvitamin D3 is AMPK-independent.

PMID- 16949050
TI  - Activation of (Na+ + K+)-ATPase induces positive inotropy in intact mouse heart
      in vivo.
AB  - OBJECTIVE: We have recently identified an activation site on (Na+ + K+)-ATPase
      and found that binding of antibody SSA412 to this specific site of the enzyme
      markedly augments (Na+ + K+)-ATPase catalytic activity. Demonstration of whether
      activation of (Na+ + K+)-ATPase affects heart function in animal in vivo was the
      object of this investigation. METHODS: Male wild-type CD-1 mouse and specific
      antibody SSA412 were used for the study. A pressure-volume micromanometer
      conductance catheter in anesthetized mouse assessed in vivo cardiac functions.
      RESULTS: Specific antibody SSA412 infusion in mouse shifted pressure-volume loop
      leftward with increased stroke volume and enhanced end-systolic elastance. Global
      systolic parameters such as ejection fraction and cardiac output, and load
      independent contractile parameters including dP/dtmax/IP, PMX/EDV, Ees, and PRSW,
      were all increased without any effect on relaxation following administration of
      SSA412. Cardiac preload indexed by EDV and afterload by ESP did not alter,
      suggesting that SSA412-enhanced myocardial performance is a direct cardiac effect
      caused by the activation of (Na+ + K+)-ATPase. CONCLUSION: Our study provides the
      first in vivo physiological evidence to demonstrate that activation of (Na+ + K+)
      ATPase induces significant positive inotropic effect in intact animal heart. The
      finding may lead to new therapeutic strategies for the treatment of heart
      failure.

PMID- 16949051
TI  - Bioengineered chondrocyte sheets may be potentially useful for the treatment of
      partial thickness defects of articular cartilage.
AB  - Some treatments for full thickness defects of articular cartilage, such as
      cultured chondrocyte transplantation, have already been done. However, to
      overcome osteoarthritis, we must further study the partial thickness defect of
      articular cartilage. It is much more difficult to repair a partial thickness
      defect because few repairing cells can address such injured sites. We herein show
      that bioengineered layered chondrocyte sheets using temperature-responsive
      culture dishes may be a potentially useful treatment for partial thickness
      defects. We evaluated the property of these sheets using real-time PCR and
      histological findings, and allografted these sheets to evaluate the effect of
      treatment using a rabbit partial model. In conclusion, layered chondrocyte sheets
      were able to maintain the cartilageous phenotype, and could be attached to the
      sites of cartilage damage which acted as a barrier to prevent a loss of
      proteoglycan from these sites and to protect them from catabolic factors in the
      joint.

PMID- 16949052
TI  - Selective LXRalpha inhibitory effects observed in plant extracts of MEH184
      (Parthenocissua tricuspidata) and MEH185 (Euscaphis japonica).
AB  - Liver X receptors (LXRs) are nuclear hormone receptors that behave as lipid
      sensors of cellular cholesterol and fatty acid. Although LXR activation can
      alleviate hypercholesterolemia by inducing cholesterol efflux, it also results in
      undesirable effects of fatty acid synthesis, resulting in hepatic steatosis and
      hyperlipidemia. Therefore, it is critical to identify LXRalpha inhibitory agents
      that would repress fatty acid synthesis and hepatic lipid accumulation. In
      current study, screening of plant extracts used for traditional oriental medicine
      resulted in the identification of two candidates demonstrating selective LXRalpha
      inhibitory activity. These were whole leaf methanol extracts of Parthenocissua
      tricuspidata (MEH184) and Euscaphis japonica (MEH185). Both MEH184 and MEH185
      decreased transcriptional activity of LXRalpha and the expression of LXRalpha
      target genes, such as FAS and ADD1/SREBP1c. Additionally, MEH184 and MEH184
      significantly reduced lipogenesis and adipocyte differentiation. Together, the
      data imply that MEH184 and MEH185 possess selective antagonistic properties on
      LXRalpha to downregulate lipogenesis.

PMID- 16949053
TI  - Circumvention and reactivation of the p53 oncogene checkpoint in mouse colon
      tumors.
AB  - The p53 tumor suppressor protein is sequence-normal in azoxymethane (AOM)-induced
      mouse colon tumors, making them a good model for human colon cancers that retain
      a wild type p53 gene. Cellular localization and co-immunoprecipitation
      experiments using a cell line derived from an AOM-induced colon tumor (AJ02-NM(0)
      cells) pointed to constitutively expressed Mdm2 as being an important negative
      regulator of p53 in these cells. Although the Mdm2 inhibitory protein p19/ARF was
      expressed in AJ02-NM(0) cells, its level of expression was not sufficient for p53
      activation. We tested the response of AJ02-NM(0) cells to the recently developed
      Mdm2 inhibitor, Nutlin-3. Nutlin-3 was found to activate p53 DNA binding in AJ02
      NM(0) cells, to a level comparable to doxorubicin and 5-fluorouracil (5-FU). In
      addition, Nutlin-3 increased expression of the p53 target genes Bax and PERP to a
      greater extent than doxorubicin or 5-FU, and triggered a G2/M phase arrest in
      these cells, compared to a G1 arrest triggered by doxorubicin and 5-FU. The
      differences in the cellular response may be related to differences in the
      kinetics of p53 activation and/or its post-translational modification status. In
      an ex vivo experiment, Nutlin-3 was found to activate p53 target gene expression
      and apoptosis in AOM-induced tumor tissue, but not in normal adjacent mucosa. Our
      data indicate that Mdm2 inhibitors may be an effective means of selectively
      targeting colon cancers that retain a sequence-normal p53 gene while sparing
      normal tissue and that the AOM model is an appropriate model for the preclinical
      development of these drugs.

PMID- 16949054
TI  - Gene expression profiling in R-flurbiprofen-treated prostate cancer: R
      Flurbiprofen regulates prostate stem cell antigen through activation of AKT
      kinase.
AB  - We have used gene expression profiling to characterize genes regulated by the
      anti-tumor non-steroidal anti-inflammatory drug (NSAID)-like agent R-flurbiprofen
      (RFB) in murine TRAMP prostate cancer. Mice with spontaneous, palpable tumors
      were treated with RFB 25 mg/(kgd) x 7d orally, or vehicle only. RNA was then
      extracted from tumor tissue and used for microarray analysis with Affymetrix
      chips. Fifty-eight genes were reproducibly regulated by RFB treatment. One of the
      most highly up-regulated genes was prostate stem cell antigen (psca). We used
      TRAMP C1 murine prostate cancer cells to examine potential mechanisms through
      which RFB could regulate psca. RFB induced dose-dependent expression of PSCA
      protein, and activity of the psca promoter, in TRAMP C1 cells in culture.
      Increased psca promoter activity was also seen following treatment of cells with
      sulindac sulfone, another NSAID-like agent, but not with celecoxib treatment. RFB
      activation of the psca promoter could be attenuated by co-transfection of
      dominant-negative akt and h-ras constructs, but not by dominant-negative mek1
      plasmids. Immunoblotting revealed that RFB increased expression of phosphorylated
      AKT at concentrations that stimulated psca promoter activity, and that increased
      PSCA protein expression. In addition, RFB-dependent up-regulation of PSCA protein
      expression could be blocked by AKT inhibitors. These data demonstrate that RFB,
      and possibly other NSAID-like analogs, can increase expression of the psca gene
      both in vivo and in culture. They further suggest the utility of combining RFB
      with AKT inhibitors or with monoclonal antibodies targeting PSCA protein, for
      treatment or prevention of prostate cancer.

PMID- 16949055
TI  - Mast cells accumulate in the anogenital region of somatosensory thalamic nuclei
      during estrus in female mice.
AB  - Mast cells are located in the mammalian thalamus where their numbers are
      sensitive to reproductive hormones. To evaluate whether differences between sexes
      and over the estrus cycle influence the nuclear distribution of mast cells in
      mice, we mounted a comprehensive analysis of their distribution in males compared
      to females and in females over the estrus cycle. Compared to males, mast cells
      were more numerous in the lateral intralaminar and posterior nuclei of females
      during estrus and in the ventral posterolateral (VPL) and medial geniculate
      nuclei during proestrus. During estrus, mast cells were especially concentrated
      in those regions within the VPL and posterior thalamic nuclei that receive
      somatosensory information from the anogenital region. Treatment of ovariectomized
      mice with estrogen increased the number and the percent of mast cells that were
      degranulated compared to that after ovariectomy alone, an effect that was most
      apparent in the lateral intralaminar, VPL and posterior nuclei. In estrogen
      primed, ovariectomized females, progesterone delivered 5 h before tissue
      collection counteracted the effects of estrogen. Cromolyn, a mast cell
      stabilizer, injected centrally 1 h prior to and 24 h after estrogen in
      ovariectomized mice, prevented the increase in number of mast cells in the whole
      thalamus and in the intralaminar, VPL and posterior nuclei. This suggests that
      estrogen induces hyperplasia by a mechanism that involves mast cell
      degranulation. Based on the discrete anatomical location of mast cells in areas
      of somatosensory nuclei that receive anogenital input together with the temporal
      correspondence of these cells with estrus, mast cells are well situated to
      influence sensory input in females during mating.

PMID- 16949056
TI  - Impact of 17beta-estradiol on cytokine-mediated apoptotic effects in primary
      hippocampal and neocortical cell cultures.
AB  - Estrogens are developmental regulators of mitochondrial apoptotic pathway in the
      central nervous system, but little is known about their involvement in cytokine
      induced apoptosis. In the present study, we evaluated effects of 17beta-estradiol
      on pro-inflammatory cytokine- and staurosporine-mediated activation of caspase-3
      and LDH-release in primary neuronal/glial cell cultures of mouse hippocampal and
      neocortical cells at different stages of their development in vitro. Enzyme
      activities were determined with colorimetric methods 6 h, 14 h, 24 h, and 48 h
      after exposure to the apoptotic agents. Biochemical data were supported at the
      cellular level by Hoechst 33342 and MAP-2 stainings, which were carried out 48 h
      after the treatment. Cytokines (co-treatment with Il-1beta and TNFalpha; 1 ng/ml)
      increased caspase-3 activity in the hippocampal and neocortical cells up to over
      200% of control values, and these effects were mostly observed on 2 and 7 days in
      vitro (DIV). Moderate, but significant cytokine-mediated increase in LDH-release
      was demonstrated in both tissues, especially on 7 and 12 DIV. Estradiol (100 nM)
      inhibited the activation of caspase-3 at early stage of development (2 DIV) in
      the hippocampal, but not in the neocortical cultures. The cytokine-induced
      activation of caspase-3 and LDH-release was inhibited by estradiol in estrogen
      receptor-independent way. These data point to a possible role of estrogens as non
      estrogen receptor-related inhibitors of cytokine-activated apoptotic pathway in
      the developing central nervous system.

PMID- 16949057
TI  - The response of magnocellular neurons of the hypothalamo-neurohyphyseal system to
      hypophysectomy, nitric oxide synthase expression as well as survival and
      regeneration in developing vs. adult rats.
AB  - This study examined the age-related changes in nitric oxide synthase
      immunoreactivity (NOS-IR), survival and regeneration of magnocellular neurons in
      the hypothalamo-neurohypophyseal system (HNS) in rats following hypophysectomy.
      In adult animal, hypophysectomy induced a significant increase in NOS-IR in the
      supraoptic (SON), paraventricular nuclei (PVN) and median eminence (ME) by 3 days
      post-lesion. NOS sustained an increased level until 2 weeks after hypophysectomy
      and then returned to normal control level. In contrast, at postnatal day 7 (PN7),
      no obvious increase in NOS-IR was observed in the SON, PVN and ME following the
      injury compared with age-matched controls. At PN14, the same injury induced an
      increase in NOS-IR in SON, PVN and ME but the increase was more transient with
      peak NOS-IR at 3 days and returning to the corresponding control level at 1 week
      after hypophysectomy. In contrast to a striking age-dependent alteration in NOS
      IR in the SON and PVN, hypophysectomy induced substantial degeneration of
      arginine vasopressin (AVP) and oxytocin (OT) neurons in the SON and PVN in both
      immature and adult rats and there was no obvious difference in neuronal survival
      after the same injury among these three groups of different ages by quantitative
      analysis. Following hypophysectomy, a large number of fibers were observed in the
      contact zone of the median eminence and the adjacent lumen of the third cerebral
      ventricle (V3) in adult rats, whereas few fibers could be found in the lumen of
      the V3 in the immature rats after the same injury. Relationships between NOS
      induction and magnocellular neuronal survival and regeneration were discussed.

PMID- 16949058
TI  - A novel teichoic acid from the cell wall of Streptomyces sp. VKM Ac-2275.
AB  - The cell wall of a pathogenic strain Streptomyces sp. VKM Ac-2275 isolated from
      potato tubers infected by scab contains a teichoic acid related to
      poly(glycosylpolyol phosphate) with a repeating unit established by chemical and
      NMR spectroscopic methods. About 60% of l-rhamnose residues bear an O-acetyl
      group at O-2 and 20% of the internal glucose residues contain an additional
      phosphate at C-4. The polymer is built of 5-6 units. This structure is found in
      bacteria for the first time. The strain is phylogenetically closest to the scab
      causing species Streptomyces scabiei and Streptomyces europaeiscabiei, but
      differs from both these species in morphological and physiological characters and
      does not produce thaxtomin A, the main phytotoxin produced by S. scabiei.

PMID- 16949059
TI  - Structure of the O-antigen of Providencia stuartii O20, a new polysaccharide
      containing 5,7-diacetamido-3,5,7,9-tetradeoxy-l-glycero-d-galacto-non-2-ulosonic
      acid.
AB  - The O-polysaccharide chain of the lipopolysaccharide (LPS) of Providencia
      stuartii O20 was found to contain d-glucuronic acid, N-acetyl-d-glucosamine, and
      a rarely occurring higher sugar 5,7-diacetamido-3,5,7,9-tetradeoxy-l-glycero-d
      galacto-non-2-ulosonic acid (di-N-acetyl-8-epilegionaminic acid, 8eLeg5Ac7Ac).
      Degradation of the LPS with dilute acetic acid caused depolymerization of the
      polysaccharide chain by the ketosidic linkage to give a tetrasaccharide
      corresponding to the repeating unit of the polysaccharide. Based on sugar and
      methylation analyses of the tetrasaccharide and O-deacylated LPS as well as
      ESIMS, (1)H and (13)C NMR spectroscopy data, the structure of the O
      polysaccharide of P. stuartii O20 was established.

PMID- 16949060
TI  - Synthesis of a benzyl-protected analog of arenarioside, a trisaccharide
      phenylpropanoid glycoside.
AB  - A benzyl-protected analog of the phenylpropanoid glycoside arenarioside, (4
      benzyloxyphenyl)ethyl alpha-L-rhamnopyranosyl-(1-->3)-4-O-[(E)-3,4-di-O-benzyl
      caffeoyl]-[beta-D-xylopyranosyl-(1-->6)]-beta-D-glucopyranoside (22), was
      synthesized through two different routes from D-glucose. This is the first
      approach on the synthesis of a trisaccharide phenylpropanoid glycoside, although
      the benzyl-protecting group in the backbone of the arenarioside analog could not
      be removed by conventional debenzylation procedures.

PMID- 16949061
TI  - Synthesis of alpha-D-Gal f-(1-->2)-D-galactitol and alpha-D-Gal f-(1-->2)[beta-D
      Gal f-(1-->3)]-D-galactitol, oligosaccharide derivatives from Bacteroides
      cellulosolvens glycoproteins.
AB  - The synthesis of alpha-D-galactofuranosyl-(1-->2)-D-galactitol, which has been
      isolated by reductive beta-elimination from glycoproteins of Bacteroides
      cellulosolvens and Clostridium thermocellum, is described. The approach of
      selective glycosylation of an aldono-1,4-lactone by the trichloroacetimidate
      method was employed. The synthesis of alpha-D-Gal f-(1-->2)[beta-D-Gal f-(1-->3)]
      D-Galol, that contains Gal f units in both anomeric configurations, is also
      reported. These are the first synthetic oligosaccharides with alpha-D-Gal f,
      previously found in natural products.

PMID- 16949062
TI  - Structural elucidation of the O-antigenic polysaccharide from enterohemorrhagic
      (EHEC) Escherichia coli O48:H21.
AB  - The structure of the antigenic O-polysaccharide (O-PS) of the lipopolysaccharide
      (LPS) produced by the enterohemorrhagic strain of Escherichia coli O48:H21 (EHEC)
      has been elucidated. The O-PS obtained by mild acid hydrolysis of the LPS had
      [alpha]D +95 (water) and was composed of L-rhamnose (L-Rha), D-galactose (D-Gal),
      2-amino-2-deoxy-D-glucose (D-GlcN), 2-amino-2-deoxy-D-galactose (D-GalN), and D
      galacturonic acid (D-GalA) (1:1:1:1:1). From the results of methylation analysis,
      mass spectrometry, 2D NMR, and DOC-PAGE, the O-PS was shown to be a high
      molecular mass polymer of a repeating pentasaccharide unit having the structure:
      [structure: see text]. The D-Gal pA non-reducing end groups in the O-PS were
      partially O-acetylated (approximately 30%) at the O-2 and O-3 positions and the
      degree of acetylation was variable from batch to batch cell production.

PMID- 16949063
TI  - Crystal structure and solid-state 13C NMR analysis of N-o-, N-m- and N-p
      nitrophenyl-2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosylamines, and their N
      acetyl derivatives.
AB  - The X-ray diffraction analysis of N-o-nitrophenyl-2,3,4,6-tetra-O-acetyl-beta-D
      glucopyranosylamine (1), N-m-nitrophenyl-2,3,4,6-tetra-O-acetyl-beta-D
      glucopyranosylamines, N-p-nitrophenyl-2,3,4,6-tetra-O-acetyl-beta-D
      glucopyranosylamines, and their N-acetyl derivatives was performed. The sugar
      moieties always adopt (4)C1 conformations, however, due to crystal packing forces
      they are always slightly distorted. It was found that except N-acetyl, N-m
      nitrophenyl-2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosylamine (5), none of the
      glucopyranosylamines studied in this paper form strong hydrogen bonds in the
      crystal lattice. Additionally, (5) crystallizes with a molecule of water, which
      occupies a special crystallographic position (on the twofold axis) and links two
      sugar molecules by hydrogen bonds. The CP MAS NMR spectra confirmed the presence
      of the intermolecular hydrogen bond involving the molecule of water in (5).
      Moreover, it was proved that in (1) an intramolecular hydrogen bond is formed
      between the glycosidic linkage and the nitro group.

PMID- 16949064
TI  - Molecular epidemiological studies in 1,3-butadiene exposed Czech workers: female
      male comparisons.
AB  - Results of a recent molecular epidemiological study of 1,3-butadiene (BD) exposed
      Czech workers, conducted to compare female to male responses, have confirmed and
      extended the findings of a previously reported males only study (HEI Research
      Report 116, 2003). The initial study found that urine concentrations of the
      metabolites 1,2-dihydroxy-4-(acetyl) butane (M1) and 1-dihydroxy-2-(N
      acetylcysteinyl)-3-butene (M2) and blood concentrations of the hemoglobin adducts
      N-[2-hydroxy-3-butenyl] valine (HB-Val) and N-[2,3,4-trihydroxy-butyl] valine
      (THB-Val) constitute excellent biomarkers of exposure, both being highly
      correlated with BD exposure levels, and that GST genotypes modulate at least one
      metabolic pathway, but that irreversible genotoxic effects such as chromosome
      aberrations and HPRT gene mutations are neither associated with BD exposure
      levels nor with worker genotypes (GST [glutathione-S-transferase]-M1, GSTT1,
      CYP2E1 (5' promoter), CYP2E1 (intron 6), EH [epoxide hydrolase] 113, EH139, ADH
      [alcohol dehydrogenase]2 and ADH3). The no observed adverse effect level (NOAEL)
      for chromosome aberrations and HPRT mutations was 1.794 mg/m(3) (0.812 ppm)--the
      mean exposure level for the highest exposed worker group in this initial study.
      The second Czech study, reported here, initiated in 2003, included 26 female
      control workers, 23 female BD exposed workers, 25 male control workers and 30
      male BD exposed workers (some repeats from the first study). Multiple external
      exposure measurements (10 full 8-h shift measures by personal monitoring per
      worker) over a 4-month period before biological sample collections showed that BD
      workplace levels were lower than in the first study. Mean 8-h TWA exposure levels
      were 0.008 mg/m(3) (0.0035 ppm) and 0.397 mg/m(3) (0.180 ppm) for female controls
      and exposed, respectively, but with individual single 8-h TWA values up to 9.793
      mg/m(3) (4.45 ppm) in the exposed group. Mean male 8-h TWA exposure levels were
      0.007 mg/m(3) (0.0032 ppm) and 0.808 mg/m(3) (0.370 ppm) for controls and
      exposed, respectively; however, the individual single 8-h TWA values up to 12.583
      mg/m(3) (5.72 ppm) in the exposed group. While the urine metabolite
      concentrations for both M1 and M2 were elevated in exposed compared to control
      females, the differences were not significant, possibly due to the relatively low
      BD exposure levels. For males, with greater BD exposures, the concentrations of
      both metabolites were significantly elevated in urine from exposed compared to
      control workers. As in the first study, urine metabolite excretion patterns in
      both sexes revealed conjugation to be the minor detoxification pathway (yielding
      the M2 metabolite) but both M1 and M2 concentration values were lower in males in
      this second study compared to their concentrations in the first, reflecting the
      lower external exposures of males in this second study compared to the first. Of
      note, females showed lower concentrations of both M1 and M2 metabolites in the
      urine per unit of BD exposure than did males while exhibiting the same M1/(M1+M2)
      ratio, reflecting the same relative utilization of the hydrolytic (producing M1)
      and the conjugation (producing M2) detoxification pathways as males. Assays for
      the N,N-(2,3-dihydroxy-1,4-butadyl) valine (pyr-Val) hemoglobin (Hb) adduct,
      which is specific for the highly genotoxic 1,2,3,4-diepoxybutane (DEB) metabolite
      of BD, have been conducted on blood samples from all participants in this second
      Czech study. Any adduct that may have been present was below the limits of
      quantitation (LOQ) for this assay for all samples, indicating that production of
      this important BD metabolite in humans is below levels produced in both mice and
      rats exposed to as little as 1.0 ppm BD by inhalation (J.A. Swenberg, M.G. Bird,
      R.J. Lewis, Future directions in butadiene risk assessment, Chem. Biol. Int.
      (2006), this issue). Results of assays for the HB-Val and THB-Val hemoglobin
      adducts are pending. HPRT mutations, determined by cloning assays, and multiple
      measures of chromosome level changes (sister-chromatid exchanges [SCE],
      aberrations determined by conventional methods and FISH) again showed no
      associations with BD exposures, confirming the findings of the initial study that
      these irreversible genotoxic changes do not arise in humans occupationally
      exposed to low levels of BD. Except for lower production of both urine
      metabolites in females, no female-male differences in response to BD exposures
      were detected in this study. As in the initial study, there were no significant
      genotype associations with the irreversible genotoxic endpoints. However, as in
      the first, differences in the metabolic detoxification of BD as reflected in
      relative amounts of the M1 and M2 urinary metabolites were associated with
      genotypes, this time both GST and EH.

PMID- 16949065
TI  - A versatile library of activity-based probes for fluorescence detection and/or
      affinity isolation of lipolytic enzymes.
AB  - This work describes the synthesis of a library of fluorescent and/or biotinylated
      alkylphosphonate inhibitors being reactive towards serine hydrolases, especially
      lipases and esterases. Fluorescent inhibitors can be used for sensitive and rapid
      detection of active proteins by gel electrophoresis. Biotinylated inhibitors are
      applicable for the enrichment and isolation of active enzymes. Functionality as
      well as the different detection methods of the synthesized inhibitors were
      successfully tested with an enzyme preparation, namely cholesterol esterase from
      porcine pancreas (ppCE). Moreover, a biotinylated inhibitor was employed to
      enrich ppCE on avidin beads. Hence, our set of phosphonate inhibitors can be used
      for the detection and/or isolation of active serine hydrolases.

PMID- 16949066
TI  - A novel mutation (C271F) in the Notch3 gene in a Chinese man with cerebral
      autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy.
AB  - BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts
      and leukoencephalopathy (CADASIL) is an adult-onset hereditary condition caused
      by mutations in the Notch3 gene. A Chinese man was studied. METHOD: Electronic
      microscopy examination of skin biopsy. The Notch3 gene was screened for mutations
      by polymerase chain reaction and direct DNA sequencing. RESULTS: Electronic
      microscopy showed the presence of deposits of granular osmiophilic material in
      dermal capillaries in the index patient. A novel heterozygous C271F in exon 6 was
      detected in the index patient. This heterozygous C271F mutation was also detected
      in the asymptomatic elder son but was not detected in the asymptomatic wife of
      the patient. Allele specific amplification showed that C271F was not detected in
      100 normal subjects. CONCLUSION: We established the molecular basis of CADASIL in
      a Chinese man. Mutation detection assay provides a reliable method for confirming
      the diagnosis of CADASIL.

PMID- 16949067
TI  - Two novel mutations of the arylsulfatase B gene in a Chinese MPS VI child
      undergoing bone marrow transplantation therapy.

PMID- 16949068
TI  - Neural stem cell properties of Muller glia in the mammalian retina: regulation by
      Notch and Wnt signaling.
AB  - The retina in adult mammals, unlike those in lower vertebrates such as fish and
      amphibians, is not known to support neurogenesis. However, when injured, the
      adult mammalian retina displays neurogenic changes, raising the possibility that
      neurogenic potential may be evolutionarily conserved and could be exploited for
      regenerative therapy. Here, we show that Muller cells, when retrospectively
      enriched from the normal retina, like their radial glial counterparts in the
      central nervous system (CNS), display cardinal features of neural stem cells
      (NSCs), i.e., they self-renew and generate all three basic cell types of the CNS.
      In addition, they possess the potential to generate retinal neurons, both in
      vitro and in vivo. We also provide direct evidence, by transplanting
      prospectively enriched injury-activated Muller cells into normal eye, that Muller
      cells have neurogenic potential and can generate retinal neurons, confirming a
      hypothesis, first proposed in lower vertebrates. This potential is likely due to
      the NSC nature of Muller cells that remains dormant under the constraint of non
      neurogenic environment of the adult normal retina. Additionally, we demonstrate
      that the mechanism of activating the dormant stem cell properties in Muller cells
      involves Wnt and Notch pathways. Together, these results identify Muller cells as
      latent NSCs in the mammalian retina and hence, may serve as a potential target
      for cellular manipulation for treating retinal degeneration.

PMID- 16949069
TI  - Climate change and the emergence of Vibrio vulnificus disease in Israel.
AB  - In 1996, a major unexplained outbreak of systemic Vibrio vulnificus infection
      erupted among Israeli fish market workers. The origins of this emergent
      infectious disease have not been fully understood. A possible link between
      climate change and disease emergence is being investigated. Meteorological
      service data from 1981, the earliest detection and reporting of V. vulnificus for
      the time in Israel, to 1998 for two stations located within the main inland fish
      farm industry were analyzed. The 1996-1998 summers were identified as the hottest
      ever recorded in Israel in the previous 40 years. Time series of monthly minimum,
      maximum, and mean temperatures showed significant increase in the summer
      temperatures along the 18 years. The highest minimum temperature value was
      recorded in summer 1996. Lag correlation analysis revealed significant
      correlations between temperature values and hospital admission dates. The
      eruption appeared 25-30 days after the extreme heat conditions in summer 1996, at
      a lag of 3 weeks in summer 1997 while the results for 1998 were at a lag of less
      than a week. Higher significant results were detected for the daily minimum
      temperatures in summer 1996 compatible with the disease eruption. These findings
      suggest that high water temperature might have impacted the ecology of our study
      area and caused the emergence of the disease, as an effect of global climate
      change.

PMID- 16949070
TI  - Blockade of Ca2+ -activated K+ channels by galantamine can also contribute to the
      potentiation of catecholamine secretion from chromaffin cells.
AB  - Galantamine is a drug in clinical use for the treatment of Alzheimer's disease,
      but its mechanism(s) of action remains controversial. Here we addressed the
      question whether galantamine could potentiate neurotransmitter release by
      inhibiting small conductance Ca2+ -activated K+ channels (KCa2). Galantamine
      potentiated catecholamine secretory responses induced by 10 s pulses of
      acetylcholine and high [K+]o applied to fast-superfused bovine adrenal chromaffin
      cell populations. Catecholamine release was significantly enhanced by galantamine
      although we did not find concentration dependence in the range 0.1-1 microM. The
      KCa2 channel blocker apamin (0.3 microM) occluded the potentiating effects of
      galantamine on acetylcholine-evoked secretion. Like apamin, galantamine also
      modified the firing of action potentials, but to a lesser extent. In addition, 1
      microM galantamine reduced by 41% the KCa2 current without modifying the voltage
      dependent Ca2+ currents. These results constitute the first direct evidence that
      galantamine can potentiate neurotransmitter release by blocking KCa2 channels, in
      addition to its already demonstrated capacity to mildly block
      acetylcholinesterase or potentiate allosterically nicotinic receptors.

PMID- 16949071
TI  - Phenylbenzopyrones structure-activity studies identify betuletol derivatives as
      potential antitumoral agents.
AB  - We have analyzed the cytotoxicity of 22 compounds with a phenylbenzo-gamma-pirone
      core structure, most of them obtained from natural sources, in five human tumor
      cell lines (HL-60, A431, SK-OV-3, HeLa and HOS). Betuletol 3-methyl ether and its
      diacetate were the most cytotoxic compounds. The HL-60 cell line was especially
      sensitive to these compounds, with IC50 values of approximately 1 microM.
      Treatment of HL-60 cells with betuletol 3-methyl ether was associated with
      apoptosis induction which was prevented by a non-specific caspase inhibitor (z
      VAD-fmk) and also by a specific inhibitor of caspase-8 (z-IETD-fmk) indicating
      activation of the extrinsic apoptotic pathway. The results suggest that betuletol
      3-methyl ether has potential as new anticancer agent.

PMID- 16949072
TI  - Pathophysiological role of mast cells in collagen-induced arthritis: study with a
      cysteinyl leukotriene receptor antagonist, montelukast.
AB  - Our previous study showed that the number of mast cells was increased in the
      inflamed paws of collagen-induced arthritis in mice, and treatment with a mast
      cell-stabilizing compound effectively suppressed the development of collagen
      induced arthritis. A recent in vitro study showed that mast cells express
      cysteinyl leukotriene type 1 receptor, and that a cysteinyl leukotriene type 1
      receptor antagonist inhibits the production of TNF-alpha by mast cells. To
      further investigate the role of mast cells in vivo, we evaluated the therapeutic
      effects of a cysteinyl leukotriene type 1 receptor antagonist, montelukast, on
      the development of collagen-induced arthritis in mice. Montelukast (10 mg/kg/day)
      or vehicle was orally administered to mice for 12 weeks, starting 6 weeks after
      immunization with bovine type II collagen. Treatment with montelukast
      significantly reduced clinical scores and X-ray scores of collagen-induced
      arthritis, and decreased the number of mast cells in the inflamed paws of
      collagen-induced arthritic mice. Immunohistochemical analysis revealed that mast
      cells in the inflamed synovium were one of the major cells producing TNF-alpha
      and that the number of TNF-alpha positive mast cells was significantly reduced by
      treatment with montelukast. Furthermore, TNF-alpha and SCF mRNA levels in the
      paws of collagen-induced arthritic mice were markedly decreased by montelukast
      treatment. Montelukast may lead to a beneficial therapeutic effect by inhibiting
      TNF-alpha production by mast cells.

PMID- 16949073
TI  - Insulin-induced vascular endothelial growth factor expression is mediated by the
      NADPH oxidase NOX3.
AB  - Vascular endothelial growth factor (VEGF) is the most potent stimulatory factor
      of angiogenesis. Its expression is induced by reactive oxygen species (ROS) in
      hypoxic conditions and by insulin in normoxic cells. Both ROS and insulin can
      activate mitogen-activated protein kinases (MAPKs) and induce the transcriptional
      factor Sp1, components that are essential for VEGF gene expression. The aim of
      this study was to investigate the role of ROS producing NADPH oxidase enzymes
      (NOX-es) in insulin-regulated VEGF gene activation. To achieve this goal we chose
      HepG2 cells as our model system as these cells express the NADPH oxidase isoform
      NOX3 and respond to insulin stimulation with enhanced ROS production and mRNA
      transcription and production of VEGF. We demonstrate that in control cells
      insulin stimulation leads to H2O2 generation, a biphasic activation of p42/44
      MAPK and the induction of both Sp1 and HIF-1alpha. Transfection of NOX3-specific
      siRNA abrogates H2O2 production and inhibits exclusively the second phase of
      p42/44 MAPK phosphorylation and Sp1 DNA binding and thus prevents upregulation of
      VEGF-A mRNA expression. In conclusion, our results demonstrate that NOX3, a ROS
      generating NADPH oxidase, plays an integral role in insulin-induced p42/44 MAPK
      signal transmission and VEGF-A production.

PMID- 16949074
TI  - KCC isoforms in a human lens epithelial cell line (B3) and lens tissue extracts.
AB  - We recently reported potassium-chloride cotransporter activity in human lens
      epithelial B3 (HLE-B3) cells. The purpose of the present study was to demonstrate
      in these cells as well as in human lens tissue the potassium-chloride cotransport
      (KCC) isoforms by reverse transcriptase-polymerase chain reaction (RT-PCR),
      Western blotting and immunofluorescence microscopy. Of the four KCC genes known
      to encode the respective proteins and their spliced variants, RT-PCR with both
      rat and human primers revealed the predicted cDNA fragments of KCC1, KCC3a,
      KCC3b, and KCC4 but not KCC2 in both HLE-B3 cells and in human lens tissue
      extracts from cataractous patients. Polyclonal rabbit (rb) anti-rat (rt) and anti
      human (hm) antibodies against rtKCC1 and hmKCC3, respectively, and a commercially
      available rb-anti-mouse (ms) KCC4 antibody were used. Rb anti-rtKCC1-ECL3
      [against epitopes within the large extracellular loop 3 (ECL3)] revealed a 150kDa
      band in HLE-B3 cells consistent with the known molecular weight of KCC1. Rb anti
      hmKCC3-ECL3 yielded three bands of 150, 122 and 105kDa, evidence for the presence
      of KCC3a, KCC3b and possibly KCC3c isoforms. The 122 and 112kDa bands were also
      demonstrated by rb anti-hmKCC3-CTD [the C-terminal domain (CTD)]. Rb anti-msKCC4
      antibody only showed a 100kDa band in HLE-B3 cells. In the human lens tissues, a
      115kDa protein was detected with rb anti-rtKCC1-ECL3 and a 100kDa band with rb
      anti-msKCC4, however, no bands with rb anti-hmKCC3-ECL3 or rb anti-hmKCC3-CTD.
      Fluorescence microscopy revealed immunocytochemical cytoplasmic and membrane
      labeling of HLE-B3 cells with anti-KCC1, -KCC3 (laser confocal microscopy) and 
      KCC4 antibodies and a Cy3-tagged secondary antibody. Hence HLE-B3 cells expressed
      proteins of the KCC1, KCC3a, b, and KCC4 isoforms, whereas surgically removed
      cataractous lens tissue expressed only those of KCC1 and KCC4.

PMID- 16949075
TI  - Cancer-selective induction of cytotoxicity by tissue-specific expression of
      targeted trans-splicing ribozyme.
AB  - For suicide gene therapy to be successfully applied for clinical settings, cancer
      restricted expression of such suicide gene should be required. We previously
      showed that group I intron from Tetrahymena can induce new RNA that exerts anti
      cancer activity through RNA replacement by trans-splicing reaction with high
      fidelity and specificity onto targeted human telomerase reverse transcriptase
      (hTERT) RNA in cancer cells, and hence the ribozyme can selectively retard growth
      of the cells in vivo as well as in vitro. However, the shortage of complete tumor
      selectivity due to telomerase expression of highly proliferating normal cells can
      limit therapeutic applicability of the hTERT-targeting approach. In this study,
      to explore the possibility of improving specificity of cancer therapy, we have
      attempted to stimulate anticancer gene activity specifically in liver cancer
      cells by tissue-specific expression of the hTERT-targeting trans-splicing
      ribozyme using liver-specific promoters. Transient transfection experiments
      demonstrated that the expression of transgene such as luciferase gene was
      specifically and highly triggered from hTERT-expressing liver cancer cells
      transfected with the ribozyme. Moreover, liver-specific expression of the
      ribozyme with diphtheria toxin A or herpes simplex virus thymidine kinase gene as
      3' exon could specifically and highly retard the growth of the hTERT-expressing
      liver cancer cells. In conclusion, we can greatly improve specificity of cancer
      cytotoxicity by combination of transcriptional targeting for tissue-specific
      transgene expression with RNA replacement for cancer-specific anticancer gene
      induction.

PMID- 16949076
TI  - Identification of the new UV filter compound cysteine-L-3-hydroxykynurenine O
      beta-d-glucoside in human lenses.
AB  - UV filters protect the human lens and retina from UV light-induced damage. Here,
      we report the identification of a new UV filter, cysteine-l-3-hydroxykynurenine O
      beta-d-glucoside, which is present in older normal human lenses. Its structure
      was confirmed by independent synthesis. It is likely this novel UV filter is
      formed in the lens by nucleophilic attack of cysteine on the unsaturated ketone
      derived from deamination of 3-hydroxykynurenine O-beta-d-glucoside. Quantitation
      studies revealed considerable variation in normal lens levels that may be traced
      to the marked instability of the cysteine adduct. The novel UV filter was not
      detected in advanced nuclear cataract lenses.

PMID- 16949077
TI  - Emergency management of corneal injuries.
AB  - Corneal injuries account for a significant proportion of the ophthalmic workload
      of most emergency departments. Although the vast majority of cases are relatively
      minor, accurate diagnosis and appropriate management are vital to prevent
      potentially sight-threatening sequelae. We present a survey of corneal injury
      cases at a general emergency department. INTRODUCTION: Corneal injuries are very
      common in both the adult and paediatric population and account for a significant
      proportion of the workload of most emergency departments. This survey assesses
      management of corneal injury cases at a general emergency department. MATERIALS
      AND METHODS: A retrospective case study was performed of 100 patients
      consecutively diagnosed with a corneal abrasion by slit lamp examination at the
      emergency department of the Chelsea and Westminster Hospital, London. Each case
      was assessed to determine documentation of set criteria including visual acuity
      (VA), treatment and grade of examiner. RESULTS: The commonest cause of injury was
      direct minor trauma (64% of cases) with contact lens related problems accounting
      for 12% of presentations. VA was documented correctly in 85 adult patients (90.4%
      of adults), incorrectly in 2 cases, and not documented at all in 7 adults (7.4%).
      VA was not recorded in paediatric cases. All cases were treated with topical
      chloramphenicol drops although frequency of treatment ranged from 2 to 5 times
      daily and duration of treatment ranged between 3 and 5 days and for 7 days. 6
      cases (6%) were assessed by an emergency nurse practitioner and the remaining
      number were seen by a casualty officer. DISCUSSION: VA must be accurately
      documented in all adult cases and should be documented in children of school age.
      A pinhole test should be performed in cases where VA is below 6/9. For analgesia,
      the use of topical nonsteroidal anti-inflammatory drugs, lubricants and bandage
      contact lens should be considered. Emergency nurse practitioners and general
      practitioners are ideally placed to follow-up uncomplicated cases.

PMID- 16949078
TI  - Modification of the Harris Hip Score in acetabular fracture treatment.
AB  - The aim of this study was to adjust the Harris Hip Score for evaluation of
      acetabular fracture treatment. The discriminating quality of the score was
      assessed. As there was low discriminating capacity at the upper end of the scale,
      with a high ceiling effect and the 60th percentile showing top points, the score
      was modified and re-evaluated. The discrimination of the modified score was
      improved, with the 90th percentile giving top points. Differences in treatment
      outcome of acetabular fractures will be easier to detect with the modified score.

PMID- 16949079
TI  - Reliability and validity of pressure ulcer diagnosis and grading: an image-based
      survey.
AB  - BACKGROUND: The reliability and validity of pressure ulcer diagnosis and grading
      are major methodological issues in studies and reports on pressure ulcer
      frequency. OBJECTIVES: The aim of the study was to estimate the reliability and
      validity of pressure ulcer diagnosis and grading within the interdisciplinary
      pressure ulcer project of the University Clinics of Essen, Germany. DESIGN: Fifty
      images of wounds from the foot/heel region and 50 images of wounds from the
      buttock/hip region were classified using a 4-grade scale. A gold standard was
      established by consensus of two senior physicians. SETTINGS: The images were
      assessed PC-based, independently by each rater. PARTICIPANTS: Five nursing
      experts and two physicians participated. METHODS: Mean simple Kappa and per cent
      agreement were calculated to assess reliability and validity. RESULTS: Mean
      simple Kappa values showed a moderate interrater agreement for grading and a fair
      interrater agreement for diagnosis. The percentage of agreements was highest for
      pressure ulcer diagnosis in the buttock/hip region with 90.5% and lowest for
      pressure ulcer grading in the buttock/hip region with 63.5%. No differences could
      be found between nurses and physicians. CONCLUSIONS: The differentiation between
      pressure ulcers and other skin lesions is rather difficult. It is important to
      assign the lower grade when the available information does not definitely support
      the higher grade. The level of agreement found was intermediate in the range of
      published results. A substantial level of agreement should be obtainable through
      further standardisation and training. Future studies should control for
      dependency in the assessment situation and dispense with the category
      "uncertain".

PMID- 16949080
TI  - Ghrelin inhibits angiotensin II-induced migration of human aortic endothelial
      cells.
AB  - Ghrelin, the endogenous ligand for the GH secretagogue receptor, is produced by
      the oxyntic cells of the stomach and is involved in the regulation of energy
      balance. However, an increasing number of direct ghrelin cardiovascular effects,
      and, among them, high ghrelin binding in atherosclerotic coronary arteries, are
      being reported. We investigated whether ghrelin affects migration of human aorta
      endothelial cells (HAEC). HAEC bound ghrelin in specific, saturable manner.
      Ghrelin, as such, did not affect HAEC migration, however it inhibited the
      angiotensin II-induced migration, and this effect was inhibited by the antagonist
      (D-Lys(3))-GHRP-6. In HAEC, ghrelin elicited increased intracellular
      concentration of cAMP that was involved in its effect on AngII-induced HAEC
      migration, as the AMP cyclase inhibitor SQ22.536 and PKA inhibitor KT5720,
      respectively, inhibited and blunted it. These findings suggest a role of ghrelin
      in the control of endothelial cell migration and its possible involvement in
      vascular changes present in disorders characterized by low plasma ghrelin.

PMID- 16949081
TI  - Dynamic shear properties of the porcine molar periodontal ligament.
AB  - The role of the periodontal ligament (PDL) is to support the tooth during
      function and resist external forces applied to it. The dominant vertical
      component of these forces is associated with shear in the PDL. Little
      information, however, is available on the dynamic behavior of the PDL in shear.
      Therefore, the present study was designed to determine the dynamic shear
      properties of the PDL in the porcine molar (n=10). From dissected mandibles
      transverse sections of the mesial root of the first molar were obtained at the
      apical and coronal levels and used for dynamic shear tests. Shear strain (0.5%,
      1.0%, and 1.5%) was applied in superoinferior direction parallel to the root axis
      with a wide range of frequencies (0.01-100 Hz). The dynamic complex and storage
      moduli increased significantly with the loading frequency, the dynamic loss
      modulus showed only a small increase. The dynamic elasticity was significantly
      larger in the coronal region than in the apical region although the dynamic
      viscosity was similar in both regions. The present results suggest that non
      linearities, compression/shear coupling, and intrinsic viscoelasticity affect the
      shear material behavior of the PDL, which might have important implications for
      load transmission from tooth to bone and vice versa.

PMID- 16949082
TI  - Sloped muscle excitation waveforms improve the accuracy of forward dynamic
      simulations.
AB  - Mathematical models of the muscle excitation are useful in forward dynamic
      simulations of human movement tasks. One objective was to demonstrate that sloped
      as opposed to rectangular excitation waveforms improve the accuracy of forward
      dynamic simulations. A second objective was to demonstrate the differences in
      simulated muscle forces using sloped versus rectangular waveforms. To fulfill
      these objectives, surface EMG signals from the triceps brachii and elbow joint
      angle were recorded and the intersegmental moment of the elbow joint was computed
      from 14 subjects who performed two cyclic elbow extension experiments at 200 and
      300 deg/s. Additionally, the surface EMG signals from the leg musculature, joint
      angles, and pedal forces were recorded and joint intersegmental moments were
      computed during a more complex pedaling task (90 rpm at 250 W). Using forward
      dynamic simulations, four optimizations were performed in which the experimental
      intersegmental moment was tracked for the elbow extension tasks and four
      optimizations were performed in which the experimental pedal angle, pedal forces,
      and joint intersegmental moments were tracked for the pedaling task. In these
      optimizations the three parameters (onset and offset time, and peak excitation)
      defining the sloped (triangular, quadratic, and Hanning) and rectangular
      excitation waveforms were varied to minimize the difference between the simulated
      and experimentally tracked quantities. For the elbow extension task, the
      intersegmental elbow moment root mean squared error, onset timing error, and
      offset timing error were less from simulations using a sloped excitation waveform
      compared to a rectangular excitation waveform (p<0.001). The average and peak
      muscle forces were from 7% to 16% larger and 20-28% larger, respectively, when
      using a rectangular excitation waveform. The tracking error for pedaling also
      decreased when using a sloped excitation waveform, with the quadratic waveform
      generating the smallest tracking errors for both tasks. These results support the
      use of sloped over rectangular excitation waveforms to establish greater
      confidence in the results of forward dynamic simulations.

PMID- 16949083
TI  - Vibration testing of a fresh-frozen human pelvis: the role of the pelvic
      ligaments.
AB  - A biodynamic model of the human pelvis is being developed in the frame of a
      research project on low back pain. In order to validate such model, the dynamic
      behaviour of the human pelvis needs to be investigated. In this study, a human
      fresh-frozen specimen comprising the three bones of the pelvic girdle and its
      ligamentous system has been used to perform vibration testing. In such test the
      response of the system to vibrations is measured at various points on the
      structure for frequencies between 10 and 340 Hz. The vibration testing is
      performed a first time on the specimen with intact ligamentous system. The
      measurements are taken two more times after subsequent bilateral resection of
      both the sacrotuberous and the sacrospinous ligaments first, and the iliolumbar
      ligaments afterwards. A comparison between the system response obtained in the
      three configurations provides information on the role of the resected ligaments
      in the dynamics of the system, thus on their relevance in the model. Results
      indicate that the sacrospinous, the sacrotuberous and the iliolumbar ligaments do
      not play a role in the pelvis dynamics as measured in this study, and will
      therefore not be represented in the biodynamic model.

PMID- 16949084
TI  - Ion-pair supercritical fluid chromatography of metoprolol and related amino
      alcohols on diol silica.
AB  - In this paper, a chromatographic system based on carbon dioxide with methanol as
      mobile phase, and diol silica as stationary phase has been investigated for
      metoprolol and related amino alcohols by addition of strong acids to systems with
      triethylamine base as primary additive. Standard conditions used were 10% of
      methanol, containing 24 mM of acid and 18 mM of triethylamine, in carbon dioxide
      with a flow rate of 1.5 ml min(-1). The column dimensions were 125 mm x 4 mm I.D.
      and kept at 40 degrees C with a back pressure of 150 bar. Effects on selectivity
      were stronger with trifluoroacetic acid than with ethanesulfonic acid. From a
      large set of related analytes, it was shown that selectivity changes were
      significant when the structure close to the nitrogen of the amino alcohol analyte
      differed. The stability of the column in the short time perspective was examined
      and it showed negligible changes. For a diastereoisomeric pair, not resolved in a
      basic system with triethylamine nor by addition of ethanesulfonic acid,
      resolution improved to about 2.1 with trifluoroacetic acid. The described
      approach offers a way to tune the selectivity of SFC systems when amines are
      analyzed without the need to change stationary phase for the chromatographic
      separation.

PMID- 16949085
TI  - Polyelectrolyte adsorption layers studied by streaming potential and particle
      deposition.
AB  - Adsorption of a cationic polyelectrolyte, polyallylamine hydrochloride (PAH),
      having a molecular weight of 70,000 on mica was characterized by the streaming
      potential method and by deposition of negative polystyrene latex particles.
      Formation of PAH layers was followed by determining the apparent zeta potential
      of surface zeta as function of bulk PAH concentration. The zeta potential was
      calculated from the streaming potential measured in the parallel-plate channel
      formed by two mica plates precovered by the polyelectrolyte. The experimental
      data were expressed as the dependence of the reduced zeta potential zeta/zeta0 on
      the PAH coverage Theta(PAH), calculated using the convective diffusion theory. It
      was found that for the ionic strength of 10(-2) M, the dependence of zeta/zeta0
      on Theta(PAH) can be reflected by the theoretical model formulated previously for
      surfaces covered by colloid particles. The electrokinetic measurements were
      complemented by particle deposition experiments on PAH-covered mica surfaces. A
      direct correlation between the polymer coverage and the initial deposition rate
      of particles, as well as the jamming coverage, was found. For ThetaPAH > 0.3 the
      initial deposition rate attained the value predicted from the convective
      diffusion theory for homogeneous surfaces. The initial deposition rates for
      surfaces modified by PAH were compared with previous experimental and theoretical
      results obtained for heterogeneous surfaces formed by preadsorption of colloid
      particles. It was revealed that negative latex deposition occurred at surfaces
      exhibiting negative apparent zeta potential, which explained the anomalous
      deposition of particles observed in previous works. It was suggested that the
      combined electrokinetic and particle deposition methods can be used for detecting
      adsorbed polyelectrolytes at surfaces for coverage range of a percent. This
      enables one to measure bulk polyelectrolyte concentrations at the level of 0.05
      ppm.

PMID- 16949086
TI  - Friction and forces between cellulose model surfaces: a comparison.
AB  - Four different cellulose model surfaces, and one silica surface, have been
      studied by means of atomic force microscopy (AFM). The normal interactions have
      been found to consist of a longer range double layer force with a short range
      steric interaction, the nature of which is extensively discussed. Both the
      surface charge and range of the steric force depend on the type of cellulose
      substrate used, as does the magnitude of the adhesion. Studies of friction reveal
      that surface roughness is the determining factor for the friction coefficient,
      with which it increases monotonically. The absolute value, however, is determined
      by the surface chemistry. All studied cellulose surfaces show similar behavior in
      response to xyloglucan addition.

PMID- 16949087
TI  - Preparation and characterization of N-methylene phosphonic and quaternized
      chitosan composite membranes for electrolyte separations.
AB  - Chitosan was functionalized either by introducing a phosphonic acid group or by
      quaternization of existing primary ammonium groups in order to make it a water
      soluble material. Functionalized chitosans and poly(vinyl alcohol) (PVA)-based
      nanoporous charged membranes were prepared in aqueous media and gelated in
      methanol at 10 degrees C to tailor their pore structure. These membranes were
      extensively characterized for their physicochemical, electrochemical, and
      permeation characteristics using FTIR, TGA, DSC, water content, ion-exchange
      capacity, ionic transport properties, and membrane permeability studies. N
      Methylene phosphonic chitosan (NMPC)/PVA-based membranes exhibited mild cation
      selectivity and quaternized chitosan (QC)/PVA composite membranes had mild anion
      selectivity, while a blend of NMPC-QC/PVA membranes exhibited weak cation
      selectivity because of formation of zwitterionic structure. Viscosity
      measurements and interaction studies for individual and mixed solutions of NMPC
      and QC were carried out for the prediction of charge interactions between -PO3H2
      and -N+(CH3)3 groups and effect on molecular weight due to functionalization.
      Elaborate electrochemical and permeation experiments were conducted in order to
      predict suitability of these membranes for the separation of mono- and bivalent
      electrolytes based on their hydrated ionic radius, and it was found that among
      all the synthesized membranes, PC/QC-30 had the highest relative permeability,
      which may extend its suitability for electrolyte separations. Observations were
      correlated with equivalent pore radius of the different membranes as estimated by
      membrane permeability measurements.

PMID- 16949088
TI  - Deposition of thin mesoporous silica films on glass substrates from basic
      solution.
AB  - Transparent thin (ca. 100 nm) films of silica-surfactant mesostructured materials
      were deposited on borosilicate glass plates and soda-lime glass tubes from
      aqueous solutions containing tetraethoxysilane, alkyltrimethylammonium chloride,
      ammonia, and methanol. By calcination in air, the films became mesoporous (BET
      surface area of 700-900 m2 g-1) with pore diameter 2.0-2.8 nm.

PMID- 16949089
TI  - Templated synthesis of silver nanowires based on the layer-by-layer assembly of
      silver with dithiodipropionic acid molecules as spacers.
AB  - The layer-by-layer assembly of silver nanoclusters with 3,3'-dithiodipropionic
      acid (DTDPA) as spacers was prepared through self-assembly on a gold foil and has
      been characterized by cyclic voltammetric and AFM techniques. The DTDPA molecules
      acting as spacers between the layers of silver serve as molecular interconnects
      for the four layers prepared in this work. The organization of layers was found
      to decrease with an increase in the number of layers. The layer-by-layer assembly
      of silver clusters motivated us to prepare silver nanowires stabilized by the
      bifunctional molecules DTDPA through template synthesis using cellulose nitrate
      membranes. The nanostructures formed by this method were characterized by SEM,
      TEM, AFM, FTIR, CV, and photoluminescence studies. It is observed that the DTDPA
      molecules, instead of forming molecular interconnects, protect the structures by
      self-assembling themselves along the edges of the nanostructures. The concept of
      self-assembly protecting the nanostructures is demonstrated in this work.

PMID- 16949090
TI  - Experimental (SERS) and theoretical (DFT) studies on the adsorption of p-, m-,
      and o-nitroaniline on gold nanoparticles.
AB  - Surface-enhanced Raman scattering (SERS) spectra of p-, m-, and o-nitroaniline
      (PNA, MNA, and ONA) adsorbed on gold nanoparticles were studied, respectively, in
      a gold colloidal solution and on dried gold-coated filter paper. Significant
      changes were found in the SERS spectra of p-, m-, and o-nitroaniline molecules
      adsorbed on the two substrates, indicating that the behavior of p-, m-, and o
      nitroaniline adsorbed on gold nanoparticles coated on filter paper was different
      from that in gold aqueous colloids. Moreover, on the filter paper it was found
      that the SERS spectra of the PNA molecules changed with the coverage density of
      the gold nanoparticles, while the MNA and ONA did not evidently change. The
      analyses showed that the origins of these changes were the different adsorption
      behavior of molecules adsorbed on the gold nanoparticles and that the adsorption
      behavior of molecules was greatly affected by the surface characteristic of the
      substrate and the surface configuration of the adsorbate. In addition, the
      vibrational frequencies and Raman scattering intensities of the three
      nitroanilines were calculated by use of the density functional theory (DFT
      B3LYP/6-31G(d)) method. The combination of SERS spectroscopy and DFT calculation
      is quite useful for studies of adsorption orientation of a molecule on a metal
      nanoparticle.

PMID- 16949091
TI  - Synthesis and dispersion of isolated high aspect ratio gold nanowires.
AB  - We report the assembly properties of high density and high aspect ratio metal
      nanowire arrays (Au, Cu and Ag with diameters ranging from 40 to 250 nm) after
      release from the anodic alumina oxide (AAO) templates. Individual Ag and Cu
      nanowires were observed following release from the template, however, in the case
      of gold nanowires, the dispersion was dependent on size and aspect ratio. 40-100
      nm gold wires aggregated to form bundles or disordered mats. We show that a
      simple cyanide-mediated release from the AAO template, results in isolated
      dispersion of wires even for the smallest wire diameters. Possible stabilising
      mechanisms for observed tendency of nanowires dispersion are discussed.

PMID- 16949092
TI  - Influence of kinetics on the determination of the surface reactivity of oxide
      suspensions by acid-base titration.
AB  - The effect of acid-base titration protocol and speed on pH measurement and
      surface charge calculation was studied on suspensions of gamma-alumina, hematite,
      goethite, and silica, whose size and porosity have been well characterized. The
      titration protocol has an important effect on surface charge calculation as well
      as on acid-base constants obtained by fitting of the titration curves. Variations
      of pH versus time after addition of acid or base to the suspension were
      interpreted as diffusion processes. Resulting apparent diffusion coefficients
      depend on the nature of the oxide and on its porosity.

PMID- 16949093
TI  - On the dynamics of liquid lenses.
AB  - The spreading of a lens of one liquid on the surface of another liquid is
      examined. Lubrication theory is used to derive a coupled system of equations for
      the air-liquid and liquid-liquid interfaces. In the case of highly viscous
      lenses, extensional stresses are promoted and an additional equation for the lens
      velocity is derived. The potential singularity at the three-phase line is
      relieved by a microscopic precursor layer of the spreading fluid assumed to be
      present ahead of the macroscopic lens. This layer is stabilised via the inclusion
      of disjoining pressure effects in the lens. The results of our full parametric
      study show that, for weak gravitational forces, the shape of the lens at
      equilibrium depends solely on the surface tension ratio for sufficiently deep
      substrate thicknesses. For thin substrates, the underlying liquid film deforms
      severely near the point of deposition exhibiting flattening and dimpling.

PMID- 16949094
TI  - Multiplexed PrEST immunization for high-throughput affinity proteomics.
AB  - Monospecific antibodies dfdfdfdf (msAbs) generated through antigen specific
      purification of polyclonal antisera are valuable tools in proteome analyses.
      However, proteome wide generation of msAbs would require extensive immunization
      programs. Therefore, it would be desirable to develop efficient immunization and
      purification methods to reduce the number of animals needed for such antibody
      based research. Here we describe a multiplex immunization strategy for generation
      of msAbs towards recombinantly produced human protein fragments, denoted PrESTs.
      Antisera from rabbits immunized with a mixture of two, three, five and up to ten
      different PrESTs have been purified by a two-step immunoaffinity-based protocol
      and the efficiency of the purification method was analyzed using a two-color
      protein array concept. The obtained results showed that almost 80% of the animals
      immunized with antigens composed of two or three different PrESTs yielded
      antibodies recognizing all the included PrESTs. Furthermore, the modified two
      step purification method effectively eliminated all background binding and
      produced pure antibody pools against individual PrESTs. This indicates that the
      multiplexed PrEST immunization strategy described here could become useful for
      high-throughput antibody-based proteomics initiatives, thus significantly
      reducing the number of animals needed in addition to providing a more cost
      efficient method for production of msAbs.

PMID- 16949095
TI  - Regulating the regulator: NF-kappaB signaling in heart.
AB  - The Nuclear Factor-kappaB (NF-kappaB) signaling pathway has been linked to
      several pathologic processes in the myocardium including cardiomyocyte
      proinflammatory cytokine release, ischemia/reperfusion injury, hypertrophy and
      apoptosis. However, very little is known about the intracellular mechanisms that
      govern NF-kappaB activity in the myocardial cells. Recent advances in our
      understanding of the regulation of NF-kappaB signaling in non-myocyte systems
      suggest that the activity of the NF-kappaB pathway is tightly regulated by a
      diversity of stress-activated signaling intermediates through direct post
      translational modification of various components of the NF-kappaB pathway. In
      this review, we will focus on these recent revelations and their implications not
      only in cardiac pathologies, but in the development of new therapeutic strategies
      to manage heart disease.

PMID- 16949096
TI  - Osmolyte trimethylamine N-oxide converts recombinant alpha-helical prion protein
      to its soluble beta-structured form at high temperature.
AB  - The thermal unfolding of full-length human recombinant alpha-helical prion
      protein (alpha-PrP) in neutral pH is reversible, whereas, in the presence of the
      osmolyte N-trimethylamine oxide (TMAO), the protein acquires a beta-sheet
      structure at higher temperatures and the thermal unfolding of the protein is
      irreversible. Lysozyme, an amyloidogenic protein similar to prion protein,
      regains alpha-helical structure on cooling from its thermally unfolded form in
      buffer and in TMAO solutions. The thermal stability of alpha-PrP decreases,
      whereas that of lysozyme increases in TMAO solution. Light-scattering and
      turbidity values indicate that beta-sheet prion protein exists as soluble
      oligomers that increase thioflavin T fluorescence and bind to 1-anilino 8
      naphthalene sulfonic acid (ANS). The oligomers are resistant to proteinase K
      digestion and during incubation for long periods they form linear amyloids>5
      microm long. The comparable fluorescence polarization of the tryptophan groups
      and their accessibility to acrylamide in alpha-PrP and oligomers indicate that
      the unstructured N-terminal segments of the protein, which contain the tryptophan
      groups, do not associate among themselves during oligomerization. Partial
      unfolding of alpha-helical prion protein in TMAO solution leads to its structural
      conversion to misfolded beta-sheet form. The formation of the misfolded prion
      protein oligomers and their polymerization to amyloids in TMAO are unusual, since
      the osmolyte generally induces denatured protein to fold to a native-like state
      and protects proteins from thermal denaturation and aggregation.

PMID- 16949098
TI  - M129V variation in the prion protein gene and psychotic disorders: relationship
      to neuropsychological and psychopathological measures.
AB  - The methionine/valine polymorphism at position 129 in the prion protein gene,
      PRNP M129V, is a known risk factor for Creutzfeldt-Jakob disease (CJD).
      Psychiatric manifestations including psychosis are common in the early phase of
      CJD and it has therefore been hypothesized that the prion protein could be
      involved in psychotic disorders. Moreover, among the various hypothesized
      functions of the prion protein, a role in synaptic activity has been described.
      We have studied the PRNP M129V variant with regard to psychotic disorders from
      two perspectives: first as a genetic risk factor and second as a genetic factor
      influencing phenotypic variation. A case-control study of 482 psychotic patients
      and 502 controls indicated that differences between patients and controls were
      not present in genotype distributions or allele frequencies. We also studied the
      influence of this variant in psychopathological symptomatology and
      neuropsychological performance in a subgroup of 159 psychotic patients. In our
      sample, patients homozygous for valine at this position presented less severe
      scores in the general psychopathological subscale (p=0.003) and in the sum of the
      total items (p=0.007) of the Positive and Negative Syndrome Scale (PANSS). Also,
      homozygote VV patients presented better scores in most neuropsychological tests,
      the most significant result of which was for delayed visual memory (p=0.021). In
      summary, our results do not support the hypothesis that M129V is a susceptibility
      factor for psychotic disorders. However, it could influence their phenotypic
      variation at the psychopathological and neuropsychological level. Independent
      replications are needed to confirm that being homozygotic for valine at PRNP
      M129V position is associated with better psychopathological and
      neuropsychological scores in psychotic disorders.

PMID- 16949097
TI  - Co-evolutionary analysis of domains in interacting proteins reveals insights into
      domain-domain interactions mediating protein-protein interactions.
AB  - Recent advances in functional genomics have helped generate large-scale high
      throughput protein interaction data. Such networks, though extremely valuable
      towards molecular level understanding of cells, do not provide any direct
      information about the regions (domains) in the proteins that mediate the
      interaction. Here, we performed co-evolutionary analysis of domains in
      interacting proteins in order to understand the degree of co-evolution of
      interacting and non-interacting domains. Using a combination of sequence and
      structural analysis, we analyzed protein-protein interactions in F1-ATPase,
      Sec23p/Sec24p, DNA-directed RNA polymerase and nuclear pore complexes, and found
      that interacting domain pair(s) for a given interaction exhibits higher level of
      co-evolution than the non-interacting domain pairs. Motivated by this finding, we
      developed a computational method to test the generality of the observed trend,
      and to predict large-scale domain-domain interactions. Given a protein-protein
      interaction, the proposed method predicts the domain pair(s) that is most likely
      to mediate the protein interaction. We applied this method on the yeast
      interactome to predict domain-domain interactions, and used known domain-domain
      interactions found in PDB crystal structures to validate our predictions. Our
      results show that the prediction accuracy of the proposed method is statistically
      significant. Comparison of our prediction results with those from two other
      methods reveals that only a fraction of predictions are shared by all the three
      methods, indicating that the proposed method can detect known interactions missed
      by other methods. We believe that the proposed method can be used with other
      methods to help identify previously unrecognized domain-domain interactions on a
      genome scale, and could potentially help reduce the search space for identifying
      interaction sites.

PMID- 16949099
TI  - Cognitive impairment and in vivo metabolites in first-episode neuroleptic-naive
      and chronic medicated schizophrenic patients: a proton magnetic resonance
      spectroscopy study.
AB  - Involvement of the prefrontal cortex in schizophrenia has been implicated by
      neuropsychological, as well as neuropathological and imaging studies. Reductions
      of N-acetylaspartate (NAA), an in vivo marker of neuronal integrity, have
      repeatedly been detected in the frontal lobes of patients with schizophrenia by
      proton magnetic resonance spectroscopy (1H-MRS). In chronic medicated patients, a
      positive correlation between NAA levels of the prefrontal cortex and cognitive
      functioning has been observed, but to date, there have been no studies in first
      episode neuroleptic-naive patients. In this study, single-voxel 1H-MRS was used
      to investigate neuronal function of the dorsolateral prefrontal cortex in 15
      first-episode and 20 chronic schizophrenic patients. Outcomes were compared to 20
      age-matched healthy controls to assess the relationship between prefrontal
      metabolism and neuropsychological performance. Patients with chronic
      schizophrenia had significant reductions of NAA, glutamate/glutamine, and choline
      levels compared to first-episode patients and healthy controls. Furthermore,
      creatine and phosphocreatine were significantly reduced in both patient groups
      compared to healthy controls. In the neuropsychological tests, chronic
      schizophrenic patients performed significantly poorer in the Auditory Verbal
      Learning Task (AVLT) compared to first-episode patients. In both patient groups,
      NAA levels of the left frontal lobe significantly correlated with performances in
      verbal learning and memory. These results corroborate data from recent structural
      and spectroscopic imaging studies of the frontal lobes in schizophrenia, in which
      cortical gray matter reductions after onset of symptoms as well as reduced levels
      of NAA in chronic, but not in first-episode schizophrenic patients have been
      reported.

PMID- 16949100
TI  - Modeling and investigation of neural activity in the thalamus.
AB  - Although it is known that electroencephalographic (EEG) spindle oscillations are
      generated and maintained in the thalamus, the underlying mechanisms are still not
      clear. In this paper, a physiologically based continuum model is used to explore
      the role of the thalamus in generation of EEG rhythms, particularly spindle
      oscillations. Furthermore, local interneurons (LIs) which were not previously
      included in such modeling are studied. A previous continuum model is extended to
      incorporate LIs within relay nuclei and self-connections of the reticular (RE)
      nucleus into investigation of the roles and functions of groups of thalamic
      neurons. The isolated thalamus is analysed into five distinct classes of
      substructures. Analysis of the properties of waves generated, leads to the main
      results that: (1) an isolated RE nucleus cannot generate spindle oscillations,
      but it is essential to generation of spindle oscillations in cooperation with the
      relay cells; (2) the LIs can also generate spindle oscillations in conjunction
      with the relay cells; (3) the self-connection loop within the LI population and
      the one within the RE nucleus both make spindle oscillations easier to produce
      than in the absence of these connections; (4) the LIs have similar effects to the
      RE nucleus, except that they are purely inhibitory, whereas the latter has both
      direct inhibitory effects on relay cells, and indirect net excitatory effects by
      inhibiting LIs which inhibit relay cells, and (6) self-connections amongst the
      LIs have equivalent effects to self-connections within the RE nucleus.

PMID- 16949101
TI  - Beautiful parents have more daughters: a further implication of the generalized
      Trivers-Willard hypothesis (gTWH).
AB  - The generalized Trivers-Willard hypothesis (gTWH) [Kanazawa, S., 2005. Big and
      tall parents have more sons: further generalizations of the Trivers-Willard
      hypothesis. J. Theor. Biol. 235, 583-590) proposes that parents who possess any
      heritable trait which increases the male reproductive success at a greater rate
      than female reproductive success in a given environment will have a higher-than
      expected offspring sex ratio, and parents who possess any heritable trait which
      increases the female reproductive success at a greater rate than male
      reproductive success in a given environment will have a lower-than-expected
      offspring sex ratio. One heritable trait which increases the reproductive success
      of daughters much more than that of sons is physical attractiveness. I therefore
      predict that physically attractive parents have a lower-than-expected offspring
      sex ratio (more daughters). Further, if beautiful parents have more daughters and
      physical attractiveness is heritable, then, over evolutionary history, women
      should gradually become more attractive than men. The analysis of the National
      Longitudinal Study of Adolescent Health (Add Health) confirm both of these
      hypotheses. Very attractive individuals are 26% less likely to have a son, and
      women are significantly more physically attractive than men in the representative
      American sample.

PMID- 16949102
TI  - Oscillatory dynamics arising from competitive inhibition and multisite
      phosphorylation.
AB  - There have been a growing number of observations of oscillating protein levels
      (p53 and NFkB) in eukaryotic signalling pathways. This has resulted in a renewed
      interest in the mechanism by which such oscillations might occur. Recent
      computational work has shown that a multisite phosphorylation mechanism such as
      that found in the MAPK cascade can theoretically exhibit bistability. The
      bistable behavior was shown to arise from sequestration and saturation mechanisms
      for the enzymes that catalyse the multisite phosphorylation cycle. These effects
      generate the positive feedback necessary for bistability. In this paper we
      describe two kinds of oscillatory dynamics which can occur in a network by which,
      both use such bistable multisite phosphorylated cycles. In the first example, the
      fully phosphorylated form of the phosphorylated cycle represses the production of
      the kinase, which carries out the phosphorylation of the unphosphorylated states
      of the cycle. The dynamics of this system leads to a relaxation oscillator. In
      the second example, we consider a cascade of two cycles, in which the fully
      phosphorylated form of the kinase, in the first cycle, phosphorylates the
      unphosphorylated forms in the second cycle. A feedback loop, by which the fully
      phosphorylated form of the second cycle inhibits the kinase step in the first
      cycle is also present. In this case we obtain a ring oscillator. Both these
      networks illustrate the versatility of the multisite bistable network.

PMID- 16949103
TI  - Development of a three-dimensional multiscale agent-based tumor model: simulating
      gene-protein interaction profiles, cell phenotypes and multicellular patterns in
      brain cancer.
AB  - Experimental evidence suggests that epidermal growth factor receptor (EGFR)
      mediated activation of the signaling protein phospholipase Cgamma plays a
      critical role in a cancer cell's phenotypic decision to either proliferate or to
      migrate at a given point in time. Here, we present a novel three-dimensional
      multiscale agent-based model to simulate this cellular decision process in the
      context of a virtual brain tumor. Each tumor cell is equipped with an EGFR gene
      protein interaction network module that also connects to a simplified cell cycle
      description. The simulation results show that over time proliferative and
      migratory cell populations not only oscillate but also directly impact the spatio
      temporal expansion patterns of the entire cancer system. The percentage change in
      the concentration of the sub-cellular interaction network's molecular components
      fluctuates, and, for the 'proliferation-to-migration' switch we find that the
      phenotype triggering molecular profile to some degree varies as the tumor system
      grows and the microenvironment changes. We discuss potential implications of
      these findings for experimental and clinical cancer research.

PMID- 16949104
TI  - Efficient cellular uptake of recombinant murine Hoxc8 homeoprotein in COS-7
      cells.
AB  - In order to analyze the self-delivery activity of Hoxc8, recombinant Hoxc8
      protein (rHoxc8) was designed to be expressed and purified in E. coli as a
      glutathione S-transferase and green fluorescent protein-fused form (GST-GFP
      Hoxc8). After purification using glutathione sepharose beads, the 82 kDa fusion
      protein was separated on the SDS-PAGE gel and confirmed by detecting the
      fluorescence through luminescent image analyzer. When rHoxc8 was added to culture
      media for 30 h, most of the COS-7 cells contained the fusion proteins, showing
      green fluorescence under the fluorescent microscope. When the efficiency of
      cellular uptake was examined after Hoechst staining, almost 100% of the cells
      exhibited the GFP signal, revealing that rHoxc8 can traverse the cellular
      membrane of COS-7 cells efficiently, suggesting that the rHoxc8 could be applied
      in the development of efficient and useful delivery vectors for therapeutic
      molecules.

PMID- 16949105
TI  - Effects of pilocarpine on the secretory acinar cells in human submandibular
      glands.
AB  - Pilocarpine has been used as a choice of drugs for treatment of impaired salivary
      flow. Although considerable data are available as to the stimulatory effect of
      pilocarpine on the salivary secretion in human, its underlying mechanism, at the
      cellular level, has not been rigorously studied. In this experiment, we studied
      the effect of pilocarpine on the ion channel activity, cytoplasmic free Ca(2+)
      concentration ([Ca(2+)](i)) and aquaporin (AQP)-5 expression, which play key
      roles in the secretary process and determine the capacity of fluid secretion. In
      human submandibular gland (SMG) acinar cells, 10(-5) M pilocarpine activated the
      outward rectifying-current, which was predominantly K(+) selective in the whole
      cell patch clamp study. The pilocarpine increased [Ca(2+)](i) in a concentration
      dependent manner in the range of 10(-6) M to 10(-4) M. We found that both
      increases of [Ca(2+)](i) and outward rectifying- K(+) current were inhibited by
      10(-5) M U-73122, a specific phospholipase C inhibitor. The magnitudes of
      pilocarpine-induced [Ca(2+)](i) transients were approximately 55% lower than
      those with the same concentration of carbachol (CCh). Pilocarpine also increased
      the amount of AQP-5 protein in the apical membrane (APM) in human SMG acinar
      cells. Our results suggest that pilocarpine induce salivary secretions in human
      by activating K(+) channels, increasing [Ca(2+)](i) via phospholipase C dependent
      pathway, and increasing AQP-5 protein expression in the APM of SMG acinar cells.

PMID- 16949106
TI  - A practical ranking system to compare toxicity of anti-fouling paints.
AB  - The toxicity of a number of new anti-fouling paints, claimed to function by
      physical means and not by leakage of toxic substances, have been tested on two
      common organisms in the Baltic Sea, i.e., the red macro alga Ceramium tenuicorne
      and the copepod Nitocra spinipes. In order to compare the toxicity between the
      paints a ranking system was developed based on the EC(50)- and LC(50)-values. The
      results showed a wide span in toxicity with the most toxic paints ranked 160
      times more toxic than the ones ranked least toxic. Also, TBT, irgarol and diuron,
      which have been used as active ingredients in traditional anti-fouling paints,
      were used to evaluate the sensitivity of the two test organisms. The results
      showed that the test organisms were equally sensitive to the substances as
      similar organisms in earlier studies. In conclusion, the ranking system presented
      in this study permits ranking and comparison of total toxicity of complex
      mixtures.

PMID- 16949108
TI  - A novel mitochondrial DNA missense mutation at G3421A in a family with maternally
      inherited diabetes and deafness.
AB  - OBJECTIVE: Mutations in mtDNA are thought to be responsible for the pathogenesis
      of maternally inherited diabetes. Here, we report a family with maternally
      inherited diabetes and deafness whose members did not harbour the mtDNA A3243G
      mutation, the most frequent point mutation in mitochondrial diabetic patients.
      This study aimed to investigate a possible other mtDNA mutation and its
      prevalence in type 2 diabetic patients. METHODS: Height, body weight, waistline,
      and hip circumference were measured and serum biochemical marks determined in all
      members of the family. In addition, a 75 g oral glucose tolerance test and
      electric listening test were conducted in these members. Genomic DNA was prepared
      from peripheral leukocytes. Direct sequencing of PCR products was used to detect
      the mtDNA mutation in this family. The prevalence of mtDNA G3421A nucleotide
      substitutions was investigated by restriction fragment length polymorphism
      analysis in 1350 unrelated type 2 diabetic patients recruited by random cluster
      sampling from the central city area of Shanghai, China. RESULTS: (1) A new
      missense homoplasmic mutation of mtDNA G3421A was found in a maternally inherited
      diabetic family and existed neither in 1350 unrelated type 2 diabetic patients
      nor in 50 non-diabetic individuals. (2) The mode of mutation and diabetes
      transmission was typical maternal inheritance in this family. (3) All diabetic
      family members were found to have an onset at 35-42 years of age, accompanied by
      deafness of varying degrees. CONCLUSION: mtDNA G3421A (Val39Ile) found in a
      family with maternally inherited diabetes and deafness is a novel missense
      mutation. Whether this is a diabetogenic mutation and its effect on mitochondrial
      function needs to be further studied.

PMID- 16949109
TI  - Specificity of mutations induced by carbon ions in budding yeast Saccharomyces
      cerevisiae.
AB  - To investigate the nature of mutations induced by accelerated ions in eukaryotic
      cells, the effects of carbon-ion irradiation were compared with those of gamma
      ray irradiation in the budding yeast Saccharomyces cerevisiae. The mutational
      effect and specificity of carbon-ion beams were studied in the URA3 gene of the
      yeast. Our experiments showed that the carbon ions generated more than 10 times
      the number of mutations induced by gamma-rays, and that the types of base changes
      induced by carbon ions include transversions (68.7%), transitions (13.7%) and
      deletions/insertions (17.6%). The transversions were mainly G:C-->T:A, and all
      the transitions were G:C-->A:T. In comparison with the surrounding sequence
      context of mutational base sites, the C residues in the 5'-AC(A/T)-3' sequence
      were found to be easily changed. Large deletions and duplications were not
      observed, whereas ion-induced mutations in Arabidopsis thaliana were mainly short
      deletions and rearrangements. The remarkable feature of yeast mutations induced
      by carbon ions was that the mutation sites were localized near the linker regions
      of nucleosomes, whereas mutations induced by gamma-ray irradiation were located
      uniformly throughout the gene.

PMID- 16949110
TI  - LTP consolidation: substrates, explanatory power, and functional significance.
AB  - Long-term potentiation (LTP) resembles memory in that it is initially unstable
      and then, over about 30 min, becomes increasingly resistant to disruption. Here
      we present an hypothesis to account for this initial consolidation effect and
      consider implications that follow from it. Anatomical studies indicate that LTP
      is accompanied by changes in spine morphology and therefore likely involves
      cytoskeletal changes. Accordingly, theta bursts initiate calpain-mediated
      proteolysis of the actin cross-linking protein spectrin and trigger actin
      polymerization in spine heads, two effects indicative of cytoskeletal
      reorganization. Polymerization occurs within 2 min, has the same threshold as
      LTP, is dependent on integrins, and becomes resistant to disruption over 30 min.
      We propose that the stabilization of the new cytoskeletal organization, and thus
      of a new spine morphology, underlies the initial phase of LTP consolidation. This
      hypothesis helps explain the diverse array of proteins and signaling cascades
      implicated in LTP, as well as the often-contradictory results about contributions
      of particular molecules. It also provides a novel explanation for why LTP is
      potently modulated by factors likely to be released during theta trains (e.g.,
      BDNF). Finally, building on evidence that normal patterns of activity reverse
      LTP, we suggest that consolidation provides a delay that allows brain networks to
      sculpt newly formed memories.

PMID- 16949112
TI  - Chronic social stress in the visible burrow system modulates stress-related gene
      expression in the bed nucleus of the stria terminalis.
AB  - Prolonged social subjugation produces physiological indices of chronic stress in
      rats. In the current study, we examined the impact of social stress on glutamic
      acid decarboxylase (GAD) isoforms, corticotropin-releasing hormone (CRH) and
      vasopressin mRNA expression in forebrain stress circuitry, using the visible
      burrow system model of dominance-subordination. Subordinate male rats develop
      behavioral and neuroendocrine changes consistent with exposure to chronic stress,
      including marked loss of body weight and elevation of basal plasma corticosterone
      relative to dominant rats. Forebrain GAD65, GAD67, CRH and vasopressin mRNA
      expression in central stress-regulatory circuits were examined by in situ
      hybridization. Elevated CRH mRNA was observed in the oval nucleus of the bed
      nucleus of the stria terminalis (BST) of subordinate males. In contrast, GAD67
      expression was decreased in the interfascicular nucleus of the BST in both the
      subordinate and dominant rats compared to non-burrow control rats. No changes in
      CRH, GAD or vasopressin were observed in amygdaloid nuclei, other BST nuclei or
      in the hypothalamic paraventricular nucleus. Collectively, these data suggest
      that exposure to the visible burrow system attenuates BST GAD expression
      regardless of social status, whereas the enhanced physiological responses to
      social stress seen in subordinates may be associated with enhanced CRH expression
      in the oval nucleus of the BST.

PMID- 16949113
TI  - GC-MS SPME profiling of rhizobacterial volatiles reveals prospective inducers of
      growth promotion and induced systemic resistance in plants.
AB  - Chemical and plant growth studies of Bacilli strains GB03 and IN937a revealed
      that the volatile components 2,3-butanediol and acetoin trigger plant growth
      promotion in Arabidopsis. Differences in growth promotion when cytokinin
      signaling mutants are exposed to GB03 versus IN937a volatiles suggest a
      divergence in chemical signaling for these two bacterial strains. To provide a
      comprehensive chemical profile of bacterial volatiles emitted from these
      biologically active strains, headspace solid phase microextraction (SPME) coupled
      with software extraction of overlapping GC-separated components was employed. Ten
      volatile metabolites already reported from GB03 and IN937a were identified as
      well as 28 compounds not previously characterized. Most of the newly identified
      compounds were branched-chain alcohols released from IN937a, at much higher
      levels than in GB03. Principal component analysis clearly separated GB03 from
      IN937a, with GB03 producing higher amounts of 3-methyl-1-butanol, 2-methyl-1
      butanol and butane-1-methoxy-3-methyl. The branched-chain alcohols share a
      similar functional motif to that of 2,3-butanediol and may afford alternative
      structural patterns for elicitors from bacterial sources.

PMID- 16949111
TI  - Mechanisms of hemispheric specialization: insights from analyses of connectivity.
AB  - Traditionally, anatomical and physiological descriptions of hemispheric
      specialization have focused on hemispheric asymmetries of local brain structure
      or local functional properties, respectively. This article reviews the current
      state of an alternative approach that aims at unraveling the causes and
      functional principles of hemispheric specialization in terms of asymmetries in
      connectivity. Starting with an overview of the historical origins of the concept
      of lateralization, we briefly review recent evidence from anatomical and
      developmental studies that asymmetries in structural connectivity may be a
      critical factor shaping hemispheric specialization. These differences in
      anatomical connectivity, which are found both at the intra- and inter-regional
      level, are likely to form the structural substrate of different functional
      principles of information processing in the two hemispheres. The main goal of
      this article is to describe how these functional principles can be characterized
      using functional neuroimaging in combination with models of functional and
      effective connectivity. We discuss the methodology of established models of
      connectivity which are applicable to data from positron emission tomography and
      functional magnetic resonance imaging and review published studies that have
      applied these approaches to characterize asymmetries of connectivity during
      lateralized tasks. Adopting a model-based approach enables functional imaging to
      proceed from mere descriptions of asymmetric activation patterns to mechanistic
      accounts of how these asymmetries are caused.

PMID- 16949114
TI  - A comparison of the population diagnosed with chlamydia in primary care with that
      diagnosed in sexual health clinics: implications for a national screening
      programme.
AB  - OBJECTIVES: To compare demographic, behavioural and HIV testing characteristics
      of individuals diagnosed with chlamydia infection in primary care with those in
      genitourinary medicine clinics, in the absence of a screening programme. The aim
      was to explore the current and potential contribution of primary care to the
      control of chlamydia. STUDY DESIGN AND METHODS: We analysed data on individuals
      who reported one or more chlamydia diagnoses in the past 5 years in a large
      probability sample survey of the resident, UK general population aged 16-44
      years. Estimates were weighted and odds ratios calculated. RESULTS: Women
      diagnosed in primary care reported fewer sexual partners, and were less likely to
      have had an HIV test in the past 5 years than their counterparts diagnosed in
      genitourinary medicine clinics. Age, ethnicity, social class, educational
      attainment and urbanization of area of residence did not differ between the two
      groups. Too few men were diagnosed in primary care to allow for such a
      comparison. CONCLUSIONS: Primary care already diagnoses a large number of women
      with chlamydia infection, who may perceive themselves as low risk through age or
      sexual behaviour, yet are likely to comprise a substantial proportion of all
      infections. Few men are diagnosed in primary care. These groups need to be
      strategically targeted in the context of a future chlamydia screening programme,
      which will focus on the screening of younger women at high risk, and in which the
      role of primary care is still in development.

PMID- 16949115
TI  - Effect of rACLF, a recombinant snake venom metallopeptidase on cell viability,
      chemokine expression and degradation of extracellular matrix proteins.
AB  - Snake venom metallopeptidases (SVMPs) comprise a family of zinc-dependent
      enzymes, which display many different biological activities. ACLF is a 23kDa
      fibrinolytic non-hemorrhagic metallopeptidase from the venom of the snake
      Agkistrodon contortrix laticinctus. We have previously developed an expression
      system for production of recombinant ACLF (rACLF) in bacteria. To achieve a
      better understanding of the role of such enzyme in envenoming cases, we have
      studied the biological properties of rACLF, including the ability of enzyme to
      degrade extracellular proteins, as well its cytotoxic effect in human fibroblasts
      and HeLa cells. Our results showed that rACLF hydrolyzed laminin, fibronectin,
      type IV collagen and thrombospondin. rACLF decreased HeLa cell viability, changed
      cell morphology and induced detachment, while for human fibroblasts no cytotoxic
      effects were observed after treatment with rACLF. In addition, growth-related
      oncogene (GRO) and monocyte chemoattractant protein 1 (MCP-1/CCL2) were
      chemokines detected in the culture supernatant of human fibroblasts incubated
      with rACLF for 48h. These chemokines could contribute to the severe local lesion
      induced by Agkistrodon contortrix lacticinctus venom. These findings suggest a
      relevant role for ACLF in envenomation.

PMID- 16949116
TI  - Elastic properties of composites: periodical homogenisation technique and
      experimental comparison using acoustic microscopy and resonant ultrasonic
      spectroscopy.
AB  - The macroscopic elastic properties of two composites (Duralumin/air and
      Duralumin/tungsten carbide (WC)) have been calculated using periodical
      homogenisation methods and the elastic properties of each phase (measured by high
      frequency acoustic microscopy). In order to check the validity of such an
      approach, acoustical resonant spectroscopy has also been applied. Thanks to the
      comparison between the resonant frequencies predicted and measured, two major
      conclusions have been obtained: the homogenisation method is very accurate for
      the composite Duralumin/air, but not for the Duralumin/WC sample: the
      experimental results are not in very good agreement with the simulation. This
      result can be then explained by the major role of interfacial state between
      Duralumin and tungsten carbide.

PMID- 16949117
TI  - Schlieren metrology for high frequency medical ultrasound.
AB  - The increased use of medical ultrasound above 40 MHz poses the challenge of
      measuring beam features that may be less than 40 microm. We have successfully
      used the optical Schlieren technique for transducers operating as high as 110
      MHz. After a brief discussion of the technique, results are presented, including
      comparisons to state-of-the-art hydrophones and wire targets.

PMID- 16949118
TI  - Basic study on apoptosis induction into cancer cells U-937 and EL-4 by ultrasound
      exposure.
AB  - Recently, the low invasive cancer treatments with small aftereffects have been
      considered. We are studying on the suppression methods of cancer cell
      proliferation with ultrasound. Cancer cells of mouse T lymphoma (EL-4) have been
      used in our study. The human histitocytic lymphoma cells (U-937) was used in this
      time. The cancer cells were cultured in a culture medium of RPMI1640. The
      standing wave acoustic field was formed in a water tank of our ultrasound
      exposure system by a vibrating plate driven with a Langevine type transducer. The
      U-937 and EL-4 were exposed to ultrasound in the acoustic field with spatial
      average acoustic intensity of 350 mW/cm(2) at 150 kHz. The viable rate of EL-4
      decreased with the lapse of culture time after ultrasound exposure. U-937 did not
      show the remarkable decrease tendency. The proliferation of U-937 which exposed
      to ultrasound with 700 mW/cm(2) was suppressed. It can be thought that apoptosis
      was induced in the cancer cells in this condition. We observed the morphological
      change on the U-937 exposed to ultrasound with this condition. The morphological
      changes by apoptosis like the shrink of cells, formation of apoptotic bodies etc.
      can be observed with an optical microscope and a phase contrast microscope.

PMID- 16949119
TI  - Design and experiment of 256-element ultrasound phased array for noninvasive
      focused ultrasound surgery.
AB  - A 256-element phased array high intensity focused ultrasound system has been
      designed and constructed in our laboratory. The 256-element spherical-section
      ultrasound phased array made from piezocomposite material operates at 1.1 MHz
      with 11-cm radius of curvature, 14-cm outer diameter, and 3.4-cm diameter central
      hole for mounting diagnostic ultrasound imaging probe. First, the explicit sound
      field calculation approach for the spherical-section phased array and the genetic
      optimal algorithm are briefly introduced as the optimal focus pattern control
      methods. Then, the design guidelines of 256-element spherical-section focused
      ultrasound phased array and 256-channel driver system are given. The results of
      single on and off axial focus, multiple on and off axial foci, half sub-array
      focus pattern provide further evidence for the 3D focus steering and sub-array
      mode for avoiding obstacles in focused ultrasound surgery. The multi-foci pattern
      can enlarge the treatment volume to 22 times larger than that of a single focus
      in one sonication. Finally, in vitro and transparent tissue-mimicking phantom
      experiment results confirm the ability of 256-element spherical-section phased
      array system to induce thermal lesions for noninvasive ultrasound surgery.

PMID- 16949120
TI  - Cell-mediated immune responses to COPV early proteins.
AB  - Cell-mediated immunity plays a key role in the regression of papillomavirus
      induced warts and intra-epithelial lesions but the target antigens that induce
      this response are not clear. Canine oral papillomavirus (COPV) infection of the
      oral cavity in dogs is a well-characterized model of mucosal papillomavirus
      infection that permits analysis of the immune events during the infectious cycle.
      In this study we show that during the COPV infectious cycle, systemic T cell
      responses to peptides of several early proteins particularly the E2 protein, as
      assayed by delayed type hypersensitivity, lymphoproliferation and IFN-gamma
      ELISPOT, can be detected. The maximal response occurs in a narrow time window
      that coincides with maximal viral DNA replication and wart regression:
      thereafter, systemic T cell responses to early proteins decline quite rapidly.
      Vaccination using particle-mediated immunotherapeutic delivery (PMID) of codon
      modified COPV E2 and E1 genes induces strong antigen-specific cell-mediated
      immune responses in the vaccinated animals. These data show that therapeutic
      immunization by PMID with codon-modified E2 is completely effective, that to E1
      is partially protective, that this correlates with the intensity of antigen
      specific cell-mediated immune responses and, further, they emphasize the
      importance of these responses and the route of immunization in the generation of
      protective immunity.

PMID- 16949121
TI  - A practical demonstration of water disinfection using TiO2 films and sunlight.
AB  - The scope of this study is the assessment of the efficiency of solar disinfection
      by heterogeneous photocatalysis with sol-gel immobilized (titanium dioxide) TiO2
      films over glass cylinders. The solar disinfection process known as SODIS was
      considered as a reference. Spring water naturally polluted with coliform bacteria
      was exposed to sunlight in plastic bottles with and without TiO2 over simple
      solar collectors and the disinfection effectiveness was measured. Total and fecal
      coliforms quantification was performed by means of the chromogenic substrate
      method in order to obtain the efficiency of each disinfection treatment. The
      disinfection with TiO2 was more efficient than the SODIS process, inactivating
      total coliforms as well as fecal coliforms. On a sunny day (more than 1000 W m(
      2) irradiance), it took the disinfection with immobilized TiO2 15 min of
      irradiation to inactivate the fecal coliforms to make them undetectable. For
      inactivation of total coliforms, 30 min was required, so that in less than half
      the time it takes SODIS, the treated water complies with the microbial standards
      for drinking water in Mexico. Another important part of this study has been to
      determine the bacterial regrowth in water after the disinfection processes were
      tested. After SODIS, bacterial regrowth of coliforms was observed. In contrast,
      when using the TiO2 catalyst, coliforms regrowth was not detected, neither for
      total nor for fecal coliforms. The disinfection process using TiO2 kept treated
      water free of coliforms at least for seven days after sun irradiation. This
      demonstration opens the possibility of application of this simple method in rural
      areas of developing countries.

PMID- 16949122
TI  - Tracking the inorganic suspended solids through biological treatment units of
      wastewater treatment plants.
AB  - From an experimental and theoretical investigation of the continuity of influent
      inorganic suspended solids (ISS) along the links connecting the primary settling
      tank (PST), fully aerobic or N removal activated sludge (AS) and anaerobic and
      aerobic digestion (AerD) unit operations, it was found that (i) the influent
      wastewater (fixed) ISS concentration is conserved through primary sludge
      anaerobic digestion, and AS and AerD unit operations. However, the measured ISS
      flux at different stages through a series of WWTP unit operations is not equal to
      the influent ISS flux because the ordinary heterotrophic organisms (OHO) biomass
      contributes to the ISS flux by differing amounts depending on the OHO (active)
      fraction of the VSS solids at that stage.

PMID- 16949123
TI  - Treatment processes for source-separated urine.
AB  - The separate collection and treatment of urine has attracted considerable
      attention in the engineering community in the last few years and is seen as a
      viable option for enhancing the flexibility of wastewater treatment systems. This
      comprehensive review focuses on the status of current urine treatment processes
      and summarises the properties of collected urine. We distinguish between seven
      main purposes of urine-treatment processes: hygienisation (storage), volume
      reduction (evaporation, freeze-thaw, reverse osmosis), stabilisation
      (acidification, nitrification), P-recovery (struvite formation), N-recovery (ion
      exchange, ammonia stripping, isobutylaldehyde-diurea (IBDU) precipitation),
      nutrient removal (anammox) and handling of micropollutants (electrodialysis,
      nanofiltration, ozonation). The review shows clearly that a wide range of
      technical options is available to treat collected urine effectively, but that
      none of these single options can accomplish all seven purposes. Depending on the
      overall goal of the treatment process, a specific technical solution or a
      combination of solutions can be found to meet the requirements. Such combinations
      are not discussed in this paper unless they are explicitly presented in the
      literature. Except for 'evaporation' and 'storage', none of the processes
      described have so far advanced beyond the laboratory stage. Considerable
      development work remains to be done to optimise urine-processing techniques in
      order to create marketable products.

PMID- 16949124
TI  - Process modeling and analysis of palm oil mill effluent treatment in an up-flow
      anaerobic sludge fixed film bioreactor using response surface methodology (RSM).
AB  - In this study, the interactive effects of feed flow rate (QF) and up-flow
      velocity (V up) on the performance of an up-flow anaerobic sludge fixed film
      (UASFF) reactor treating palm oil mill effluent (POME) were investigated. Long
      term performance of the UASFF reactor was first examined with raw POME at a
      hydraulic loading rate (HRT) of 3 d and an influent COD concentration of 44300
      mg/l. Extreme reactor instability was observed after 25 d. Raw POME was then
      chemically pretreated and used as feed. Anaerobic digestion of pretreated POME
      was modeled and analyzed with two operating variables, i.e. feed flow rate and up
      flow velocity. Experiments were conducted based on a central composite face
      centered design (CCFD) and analyzed using response surface methodology (RSM). The
      region of exploration for digestion of the pretreated POME was taken as the area
      enclosed by the feed flow rate (1.01, 7.63 l/d) and up-flow velocity (0.2, 3 m/h)
      boundaries. Twelve dependent parameters were either directly measured or
      calculated as response. These parameters were total COD (TCOD) removal, soluble
      COD (SCOD) removal, effluent pH, effluent total volatile fatty acid (TVFA),
      effluent bicarbonate alkalinity (BA), effluent total suspended solids (TSS), CH4
      percentage in biogas, methane yield (Y M), specific methanogenic activity (SMA),
      food-to-sludge ratio (F/M), sludge height in the UASB portion and solid retention
      time (SRT). The optimum conditions for POME treatment were found to be 2.45 l/d
      and 0.75 m/h for QF and V up, respectively (corresponding to HRT of 1.5 d and
      recycle ratio of 23.4:1). The present study provides valuable information about
      interrelations of quality and process parameters at different values of the
      operating variables.

PMID- 16949125
TI  - Determining the domestic specific loads of two wastewater plants of the Paris
      conurbation (France) with contrasted treatments: a step for exploring the effects
      of the application of the European Directive.
AB  - The effluents of wastewater treatment plants (WTTP) discharged into the rivers
      considerably affect the biogeochemical functioning of the system. In this paper,
      we characterize both raw and treated domestic wastewater from two WTTPs of
      Parisian agglomeration using different process treatments (Acheres WWTP with a
      secondary treatment and Colombes WWTP with a tertiary one). In addition to the
      classical variables, we analyse the input of bacteria, both the heterotrophs and
      the nitrifyers. Tertiary treatment leads to significantly decrease ammonium
      specific load (< 2 g KjN inhab equ.(-1) instead of 9 g KjN inhab equ.(-1) for
      secondary treatment) and notably reduces the one of organic matter (approximately
      2.5 g biological oxygen demand (BOD) inhab equ.(-1) instead of approximately 7.5
      g BOD inhab equ.(-1) for secondary treatment); it is therefore promising to
      improve oxygen status of both the Seine river and its estuary. In terms of total
      bacterial biomass abatement (the heterotrophs mostly), bioreactors (at Colombes
      WWTP) eliminate 12% more bacterial biomass than the activated sludge treatment
      (at Acheres WWTP). Regarding the nitrifying bacteria, a tertiary treatment in
      bioreactors eliminates reverse similar 90% of both nitrifying bacteria and
      nitrogen pollution of wastewater. Bacterial populations are characterized by
      large size bacteria (> 1 microm) with a higher growth rate, that represent in the
      treatment plant effluents 70% of the biomass. These large size bacteria have
      therefore a strong impact in the organic matter degradation and oxygen
      consumption. Relationships between classical physical-chemical variables
      routinely analysed in WWTPs laboratory and bacterial biomass (heterotrophic and
      nitrifying) are established, in order to quantify the ecological role of the
      allochthonous bacteria brought into the river system. In addition, domestic
      specific loads are calculated for both raw and treated effluents of the two types
      of WWTPs. As the application of the European Water Directive requires to upgrade
      the wastewater treatment at Acheres WWTP as soon as 2007 for 90% nitrification
      and 30% denitrification and in 2015 for further denitrification (up to 70%), the
      results of this study can be taken as point-source constraints into the modelling
      approach already developed for the Seine basin, and chosen to test the
      implementation of the Water Frame Directive.

PMID- 16949126
TI  - Mechanistic differences between in vitro assays for hydrazone-based small
      molecule inhibitors of anthrax lethal factor.
AB  - A systematically generated series of hydrazones were analyzed as potential
      inhibitors of anthrax lethal factor. The hydrazones were screened using one UV
      based and two fluorescence-based in vitro assays. The study identified several
      inhibitors with IC50 values in the micromolar range, and importantly, significant
      differences in the types of inhibition were observed with the different assays.

PMID- 16949127
TI  - Photosensitized reduction of DDT using visible light: the intermediates and
      pathways of dechlorination.
AB  - A reaction mixture containing DDT (1,1,1-trichloro-2,2-bis(p
      chlorophenyl)ethane), methylene green (as the photosensitizer), and triethylamine
      (as the electron donor) in acetonitrile:water (1:1) was irradiated by an ordinary
      150-W GE-Miser spotlight to facilitate visible-light photosensitized DDT
      dehalogenation. The intermediates and reaction products were identified by GC/MS
      (gas chromatography/mass spectrometer) and NMR (nuclear magnetic resonance). The
      photosensitized dehalogenation method partially degraded DDT via an electron
      transfer relay mechanism. Results indicate that DDT lost about three chlorines
      after a total of 19 days of irradiation. Aliphatic chlorines were found to be
      removed easier than aromatic chlorines. Various types of reductants were compared
      for electron donation efficiency, and photosensitizer concentration was optimized
      for our reaction system. In most cases, clean and simple dechlorinated products
      were observed. The proposed photosensitized reduction was coexisted with a
      thermal elimination effect for the first chlorine removal of DDT, and the
      photosensitized electron transfer reduction was shown to be the dominating
      mechanism responsible for further dechlorination after the initial stage. A
      sequential dechlorination pathway was proposed, with each successive
      dehalogenation, the reaction proceeds more slowly. The results have shown the
      feasibility of utilizing visible light, nontoxic dyes and electron donors to
      render a toxic compound less toxic and to enhance the natural carbon regeneration
      rates.

PMID- 16949128
TI  - An inventory of N(2)O emissions from agriculture in China using precipitation
      rectified emission factor and background emission.
AB  - Fertilized agricultural soils are a major anthropogenic source of atmospheric
      N(2)O. A credible national inventory of agricultural N(2)O emission would benefit
      its global strength estimate. We compiled a worldwide database of N(2)O emissions
      from fertilized fields that were consecutively measured for more than or close to
      one year. Both nitrogen input (N) and precipitation (P) were found to be largely
      responsible for temporal and spatial variabilities in annual N(2)O fluxes (N(2)O
      N). Thus, we established an empirical model (N(2)O-N=1.49 P+0.0186 P.N), in which
      both emission factor and background emission for N(2)O were rectified by
      precipitation. In this model, annual N(2)O emission consists of a background
      emission of 1.49 P and a fertilizer-induced emission of 0.0186 P.N. We used this
      model to develop a spatial inventory at the 10x10km scale of direct N(2)O
      emissions from agriculture in China. N(2)O emissions from rice paddies were
      separately quantified using a cropping-specific emission factor. Annual
      fertilizer-induced N(2)O emissions amounted to 198.89GgN(2)O-N in 1997,
      consisting of 18.50GgN(2)O-N from rice paddies and 180.39GgN(2)O-N from
      fertilized uplands. Annual background emissions and total emissions of N(2)O from
      agriculture were estimated to be 92.78GgN(2)O-N and 291.67GgN(2)O-N,
      respectively. The annual direct N(2)O emission accounted for 0.92% of the applied
      N with an uncertainty of 29%. The highest N(2)O fluxes occurred in East China as
      compared with the least fluxes in West China.

PMID- 16949129
TI  - Arsenic release from iron rich mineral processing waste: Influence of pH and
      redox potential.
AB  - This paper presents the effect of pH and redox potential on the potential
      mobility of arsenic (As) from a contaminated mineral processing waste. The
      selected waste contained about 0.47 g kg(-1) of As and 66.2 g kg(-1) of iron
      (Fe). The characteristic of the waste was identified by acid digestion, X-ray
      diffraction and sequential extraction procedures. Less than 2% of the total As
      was acid extractable with the remaining 98% associated with Fe-oxyhydroxides and
      oxides. Batch leaching tests at different pH conditions showed a strong pH
      dependence on arsenic and iron leaching. Arsenic leaching followed a "V" shaped
      profiles with significant leaching in the acidic and alkaline pH region. Acid
      extractable phases dissolved at acidic pH, while desorption of arsenic due to
      increase in pH resulted in high arsenic concentration at alkaline pH. Under
      aerobic conditions and pH 7, As solubility was low, probably due to its
      precipitation on Fe-oxyhydroxides. Maximum As solubilization occurred at pH 11
      (3.59 mg l(-1)). Similarity in the As and Fe leaching profiles suggested that the
      release of As was related to the dissolution of Fe in the low pH region. In
      general, redox potential did not play a significant role in arsenic or iron
      solubilization. It was thus concluded that for this solid waste, desorption was
      the predominant mechanism in arsenic leaching. A simple thermodynamic model based
      on arsenic and iron redox reactions was developed to identify the more sensitive
      redox couple.

PMID- 16949130
TI  - Mercury levels and liver pathology in feral fish living in the vicinity of a
      mercury cell chlor-alkali factory.
AB  - Twenty-three barbels (Barbus graellsii), 30 bleaks (Alburnus alburnus) and 4
      sediment samples were collected from four areas of the Cinca River (NE Spain),
      upstream and downstream of a mercury cell chlor-alkali plant. Mercury
      concentration in sediments downstream of the plant was about 25 times higher than
      the concentration upstream. Mercury levels in the muscle and liver of barbels
      downstream of the chlor-alkali plant were 10 and 30 times higher than those
      upstream. The average mercury concentration in the muscle and liver of barbels
      downstream of the factory was 1.48 and 1.78mg/kgw.w., with maximal concentrations
      of 2.43 and 3.64mg/kgw.w, respectively. Liver/muscle ratio of mercury was
      significantly higher in barbels sampled downstream of the factory. Bleak showed a
      similar pattern, with a significantly higher whole-body mercury concentration
      downstream of the chlor-alkali plant. Nevertheless, a progressive decrease in
      mercury concentration downstream of the impact area was found in bleak, but not
      in barbel. Histopathological analysis showed that fish downstream of the factory
      had significantly higher prevalence of liver pathologies (p<0.05). Although there
      are no specific histopathological markers of mercury exposure, barbels with the
      highest Hg levels in the liver also showed the most severe pathologies, and the
      processes found in these barbels were consistent with the pro-oxidant effect of
      heavy metals.

PMID- 16949131
TI  - Depletion of selected polychlorinated biphenyl, dibenzodioxin, and dibenzofuran
      congeners in farmed rainbow trout (Oncorhynchus mykiss): a hint for safer fish
      farming.
AB  - Farmed fish can be exposed to persistent organic contaminants--such as
      polychlorinated biphenyls (PCBs), dibenzodioxins (PCDDs), and dibenzofurans
      (PCDFs)--via feed, this eventually resulting in accumulation levels of health
      concern. To study the correlation between feed contamination, chemical
      accumulation in fish muscle (fillet), and chemical depletion, an all-vegetal base
      (or blank) feed was prepared and fortified with a commercial PCB mixture (Aroclor
      1254) and six PCDD and PCDF congeners (namely, 2,3,7,8-T(4)CDD, 2,3,7,8-T(4)CDF,
      1,2,3,7,8-P(5)CDD, 1,2,3,7,8-P(5)CDF, O(8)CDD, and O(8)CDF) to reproduce
      realistic low, medium, and high contamination levels. After a 1-month exposure,
      trout (Oncorhynchus mykiss) were fed with the blank feed and sacrificed every 0.5
      months over a 3-month period from exposure end; fillet specimens were sampled at
      each time. In all groups, the average fish weight increased linearly through the
      observation period. The chemical diminishing patterns observed were due to the
      combined effect of clearance and growth dilution: for 10 PCB and four PCDD and
      PCDF congeners, patterns were described with an empirical one-compartment (fish
      muscle) model. The canonical pseudo-first-order kinetic equation used was also
      modified into the form C=[C(0)exp(-k(C)t)] (m(W)t+1)(-1) to distinguish between
      the contributions to depletion from clearance, exp(-k(C)t), and growth dilution,
      (m(W)t+1)(-1). Most mean clearance half-life (HL(C)) estimates appear to be
      greater than 4 months, in a number of cases reaching magnitudes well over 10
      months or even negative, thus clearly indicating a non-negligible contribution
      from a second compartment. Based on means and their 95% confidence intervals, the
      depletion HL(D) estimates of the 14 selected congeners seem to be comprised
      between 1.2-3.4 and 1.0-5.0 months, respectively: these values, accounting for
      both clearance and growth dilution, provide an indication of the relevance of a
      blank feed as a management option to reduce the overall PCB, PCDD, and PCDF
      content in farmed trout. Due to a lack of bioaccumulation, O(8)CDD and O(8)CDF
      yielded no results for evaluation, whereas for many PCB congeners results were
      insufficient for empirical modelling.

PMID- 16949132
TI  - Quantification of ecotoxicological tests based on bioluminescence using Polaroid
      film.
AB  - Assays based on the measurement of bacterial luminescence are widely used in
      ecotoxicology. Bacterial strains responding either to general toxicity or
      specific pollutants are rapid, cost-effective and easy to use. However,
      quantification of the signal requires relatively expensive instrumentation. We
      show here that the detection of luminescence of BioTox, a Vibrio fischeri-based
      toxicity test, and of a specific recombinant bacterial strain for arsenic
      determination, is possible using common Polaroid film. The exposed films can be
      used for visual or computer-assisted quantification of the signal. Qualitative
      visual comparison to standards can be used in the rapid and relatively accurate
      estimation of toxicity or pollutant concentration. The computer-assisted method
      significantly improves the accuracy and quantification of the results. The
      results obtained by computer-assisted quantification were in good agreement with
      the values obtained with a luminometer.

PMID- 16949133
TI  - Middle Pleistocene handaxes from the Korean Peninsula.
AB  - We present four biface assemblages from an archaeologically poorly known region
      of the Old World: Middle Pleistocene Korea. The handaxes are derived from a
      series of Middle Pleistocene localities in the Imjin/Hantan River Basins (IHRB)
      in Korea. The best known of these localities is Chongokni, although a number of
      equally important sites in the IHRB have been discovered and excavated over the
      course of the past two decades (e.g., Kumpari, Chuwoli, and Kawoli). Reanalysis
      of the age of the Chongokni deposits suggests a hominin occupation between 350
      300 ka. Comparative study of the IHRB handaxes with the well-known bifacial
      implements from Olorgesailie (Kenya) and Hunsgi-Baichbal (India) indicates that
      the often-noted "thick" trait of the East Asian handaxes differs at a statistical
      level across the various regions of the Old World. The finds from the IHRB sites,
      and the Chinese sites of Bose and Dingcun that contain handaxes-like implement,
      question the validity of the Movius Line sensu stricto. However, why East Asian
      Middle Pleistocene hominins did not consistently produce more refined bifaces
      across broader regional and/or temporal facies, remains open to question. Thus,
      the absence of similar sites in wider areas of Early and Middle Pleistocene East
      Asia suggests that the Movius Line sensu lato is still supportable and warrants
      additional detailed cross comparative studies of the stone toolkits east and west
      of the line.

PMID- 16949134
TI  - Atrophy-related ubiquitin ligases, atrogin-1 and MuRF1 are up-regulated in aged
      rat Tibialis Anterior muscle.
AB  - A phenotypic feature of aging is skeletal muscle wasting. It is characterized by
      a loss of muscle mass and strength. Age-related loss of muscle mass occurs
      through a reduction in the rate of protein synthesis, an increase in protein
      degradation or a combination of both. However, the underlying mechanism is still
      poorly understood. To test the hypothesis that the ubiquitin-proteasome pathway
      contributes to this phenomenon, we studied MuRF1 and atrogin-1 expression in
      Tibialis Anterior muscle of aged rats. These two E3 ligases are considered as
      sensitive markers of muscle protein degradation by the ubiquitin-proteasome
      system. Our results revealed that, in skeletal muscle of aged rats, the decline
      in muscle mass is accompanied by an increase in the level of oxidized proteins
      and ubiquitin conjugates (90%) whereas the functionality of the proteasome
      remains constant compared to young rats. Furthermore, the level of both MuRF1 and
      atrogin-1 mRNA is markedly up-regulated in aged muscle (respectively x2 and
      x2.5). Taken together these data argue for the involvement of the ubiquitin
      proteasome pathway in sarcopenia of fast-twitch muscle, in particular through
      increased expression of MuRF1 and atrogin-1. Moreover, we observed a decrease in
      the IGF-1/Akt signalling pathways and elevated level of TNFalpha mRNA in aged rat
      muscle. Therefore, IGF-1/Akt and TNFalpha represent potential mediators
      implicated in the regulation of MuRF1 and atrogin-1 genes during aging.

PMID- 16949135
TI  - Strongyloides stercoralis hyperinfection in systemic lupus erythematosus and the
      antiphospholipid syndrome.
AB  - OBJECTIVE: The Strongyloides stercoralis hyperinfection syndrome (SHS) may
      develop in individuals with asymptomatic infection receiving immunosuppressive
      treatment. This report summarizes current knowledge regarding SHS in patients
      with systemic lupus erythematosus (SLE) and associated antiphospholipid syndrome
      (APS). METHODS: Two patients with active SLE and associated APS presenting with
      SHS are reported. Additional cases of strongyloidiasis in SLE were identified and
      reviewed. RESULTS: Patient 1: A 34-year-old woman with SLE and APS characterized
      by active glomerulonephritis, stroke, and several hospital-acquired infections
      presented with vomiting and diffuse abdominal pain. Intestinal vasculitis was
      suspected, and treatment with methylprednisolone and cyclophosphamide was given.
      Response was partial. A gastric biopsy revealed S. stercoralis larvae. She
      received ivermectin and eventually recovered. Patient 2: A 37-year-old man with
      active glomerulonephritis and APS with recurrent thrombosis presented with
      digital necrosis. Necrotizing vasculitis was suspected and treated with
      immunosupressants. He suddenly developed respiratory failure secondary to
      alveolar hemorrhage and bronchoalveolar lavage was performed. The patient
      developed Gram-negative septic shock and died. The postmortem result of
      bronchoalveolar lavage yielded Strongyloides larvae. Nine cases of
      strongyloidiasis and the SHS in SLE patients reported in the literature were
      identified and reviewed. Five of these patients died; none had associated APS.
      CONCLUSIONS: These cases suggest that the SHS can exacerbate SLE and APS,
      predisposing to Gram-negative sepsis and death. Immunocompromised patients need
      an early diagnosis and specific treatment of parasitic diseases and their
      complications. The SHS should be considered in the differential diagnosis of
      lupus complications in patients from endemic areas.

PMID- 16949136
TI  - Pathogenesis and management of adult-onset Still's disease.
AB  - OBJECTIVE: To review recent literature regarding the pathogenesis and treatment
      of adult-onset Still's disease (AOSD). METHODS: We searched MEDLINE and PUBMED
      from 1971 to present using the following terms: adult-onset Still's disease,
      AOSD, or adult Still's disease. In addition we manually retrieved relevant
      abstracts from recent American College of Rheumatology and European League
      Against Rheumatism meetings. RESULTS: The etiology of AOSD, a rare, immune
      mediated, multisystem inflammatory disorder characterized by quotidian spiking
      fevers, evanescent rash, and arthritis, remains unknown. An infectious etiology
      has been postulated, although a definitive agent has yet to be identified.
      Cytokines, such as interleukin (IL)-1, IL-6, interferon (IFN)-gamma, and tumor
      necrosis factor-alpha, are elevated in patients with AOSD. IL-18 and macrophage
      colony stimulating factor also seem to play a role. Treatment historically
      consisted of nonsteroidal antiinflammatory drugs, often in combination with low
      dose corticosteroids. Immunosuppressants (mainly methotrexate, but also
      intramuscular gold, azathioprine, cyclosporine A, leflunomide, and
      cyclophosphamide) and intravenous gamma-globulin are efficacious and have been
      used as steroid-sparing drugs. The recently reported use of anticytokine (anti
      TNF-alpha, anti-IL-1, and anti-IL-6) agents in refractory cases has opened new
      horizons in the treatment of AOSD and provided important clues for its
      pathophysiology. CONCLUSIONS: Advances in immunology have enhanced our
      understanding of the role of cytokines in AOSD pathogenesis. Early, promising
      studies of anticytokine agents in AOSD may provide further insight into the
      pathogenetic mechanisms of this complex disease.

PMID- 16949137
TI  - D-dimer and inflammatory markers in the peripheral arterial disease.

PMID- 16949138
TI  - Demographic, risk factor, and knowledge differences between Latinas and non
      Latinas referred to colposcopy.
AB  - OBJECTIVE: Disparities occur in the incidence and mortality of cervical cancer
      among minority women in the US. Screening lowers cervical cancer incidence.
      Screening rates are lower for minority women than for White women in the US. This
      study sought to identify demographic, risk factor, and perception of the role of
      Pap smears between Latinas and non-Latinas. METHODS: A written survey was
      administered to 150 Latinas and 150 non-Latinas attending a colposcopy unit. Data
      on demographics, risk factors, screening rates, knowledge about cervical cancer
      screening, and perceived barriers to participation in screening programs were
      collected. RESULTS: A total of 140 Latinas and 146 non-Latinas completed the
      survey. Marital status and health insurance status were similar in the two
      groups. 30% of Latinas and 73.3% of non-Latinas reported completing college
      (p<0.0001). Only 55.7% of Latinas were employed, compared to 82.2% of non-Latinas
      (p<0.0001). 21% of Latinas and 53.4% of non-Latinas reported an annual income
      greater than 35,000 dollars (p<0.0001). Among Latinas, women with 1-5 lifetime
      Pap smears were less likely to have completed college than those with more than 5
      lifetime Pap smears (OR=2.11; 95% CI 1.05-4.22) and to have an annual income of
      less than 35,000 dollars (OR=3.81; 95% CI 1.64-8.87). Latinas were less likely to
      have > or =6 lifetime sexual partners, use tobacco, and have a history of
      sexually transmitted infections. Latinas more commonly reported fear of test
      results (OR, 0.04; 95% CI 0.02-0.09) and inability to communicate with their
      provider in Spanish (p<0.0001) as barriers to screening than the non-Latina
      respondents. CONCLUSIONS: Several of the barriers limiting access to cervical
      cancer screening programs are also present among screened Latinas undergoing
      further evaluation for abnormal Pap smears.

PMID- 16949139
TI  - Estrogen and the development and protection of nigrostriatal dopaminergic
      neurons: concerted action of a multitude of signals, protective molecules, and
      growth factors.
AB  - The nigrostriatal dopamine system comprises the dopaminergic neurons located in
      the ventral midbrain, their axonal connections to the forebrain, and their direct
      cellular target cells in the striatal complex, i.e. GABAergic neurons. The major
      function of the nigrostriatal dopaminergic unit is the coordination and fine
      tuning of motor functions at the extrapyramidal level. Numerous biologically
      active factors including different types of growth factors (neurotrophins,
      members of the TGFbeta family, IGFs) and peptide/steroid hormones have been
      identified in the past to be implicated in the regulation of developmental
      aspects of this neural system. Some of these developmentally active determinants
      have in addition been found to play a crucial role in the mediation of
      neuroprotection concerning dopaminergic neurons. Estrogen was identified as such
      a compound interfering with embryonic neuronal differentiation and cell survival.
      The physiological mechanisms underlying these effects are very complex and
      include interactions with other developmental signals (growth factors),
      inflammatory processes as well as apoptotic events, but also require the
      activation of nonneuronal cells such as astrocytes. It appears that estrogen is
      assuming control over or at least influences a multitude of developmental and
      protective cellular mechanisms rather than taking over the part of a singular
      protagonist.

PMID- 16949140
TI  - Pharmacological and genetic influences on hole-board behaviors in mice.
AB  - Head dipping on a hole-board is frequently used as an indicator of exploratory
      tendencies in rodent studies. Drugs with diverse pharmacological properties alter
      head dipping suggesting that many neurotransmitter systems are involved in the
      expression of exploratory behavior. The aim of the current experiments was to
      determine the effects of several drugs from different classes on head dipping,
      and to compare the effects of some of these agents in lines of mice that have
      been selectively bred for divergent expression of head dipping on a hole-board.
      In the current experiments, the effects on head dipping of three doses each of
      fluoxetine, desipramine, GBR-12909, methamphetamine, pentylenetetrazol, and
      diazepam were evaluated in genetically heterogeneous mice. Most drugs altered the
      number of head dips in a predictable manner, but the effects on locomotion were
      generally as large as those seen for head dipping. Locomotion could completely
      account for the effects of fluoxetine and pentylenetetrazol, and to a lesser
      extent, diazepam. We have also developed replicate lines of mice selectively bred
      for high (High Exploratory Behavior: HEB) or low (Low Exploratory Behavior: LEB)
      head dipping on a hole-board and evaluated the effects of diazepam and
      methamphetamine on hole-board behaviors in these mice. Diazepam increased head
      dipping and locomotion equivalently in both lines of mice, but methamphetamine
      stimulated locomotion in HEB mice more than in LEB mice. These results broadly
      suggest that the effects of most drugs we tested are not specific for head
      dipping, since almost all drugs tested affected head dipping and locomotion
      equivalently. However, the results with the genetically heterogeneous mice and
      HEB and LEB mice suggest that some aspects of the dopaminergic system are
      involved in head dipping.

PMID- 16949141
TI  - Uncovering differences across the cancer control continuum: a comparison of
      ethnic and mainstream cancer newspaper stories.
AB  - OBJECTIVE: The use of the news media to disseminate control research could play a
      pivotal role in reducing the cancer burden. An important first step is to
      understand how newspapers cover cancer and if differences exist between
      mainstream and ethnic newspapers. METHODS: Cancer news in the major U.S. (MAJN)
      (N=5327) and ethnic (ENW) newspapers (N=565) appearing in 2003 were content
      analyzed. Comparisons of mainstream and ethnic newspapers utilized Pearson x(2)
      tests of two-sided statistical significance and independent samples t tests for
      interval-level variables. RESULTS: Breast cancer dominated coverage: 27% of MAJN
      and 35% of ENW stories mentioned breast cancer. Coverage focused primarily on
      cancer treatment (MAJN: 60%; ENW: 52%) rather than on primary or secondary
      prevention. Compared to mainstream newspapers, the ethnic newspapers required
      lower literacy levels for understanding news stories, were substantially more
      likely to cover primary and secondary cancer prevention, and paid more attention
      to cancer awareness and education. CONCLUSIONS: The ethnic media are a promising
      vehicle for dissemination of cancer control messages. However, the successful
      utilization of any U.S. newspaper as a dissemination mechanism requires a greater
      understanding of the root causes for imbalances in cancer coverage and work with
      journalists to reframe cancer news coverage.

PMID- 16949142
TI  - Dietary fat, coronary heart disease, and cancer: a historical review.
AB  - OBJECTIVES: This report describes the historical development of medical theories
      and research concerning the relationship between dietary fat intake and breast
      and colorectal cancer and coronary heart disease (CHD). METHOD: The historical
      and medical literature on this topic was analyzed with special reference to the
      Woman's Health Initiative (WHI) studies. RESULTS: After 1900, changes in clothing
      fashions and life insurance mortality studies created strong preferences for
      slimness and emphasized reduced dietary fat intake as the preferred method of
      weight control. After midcentury, ecological correlations of countries found that
      national average dietary fat intake was related to national breast cancer and CHD
      rates. These relationships were not found in longitudinal studies of the same
      countries or in studies of dietary fat intake of individuals, including the WHI
      study. Dietary fat intake was found to affect colorectal cancer in some studies
      of individuals, although not the WHI. The WHI, like other intervention studies of
      dietary fat reduction, used unrepresentative samples and costly lifestyle change
      techniques that are not economically feasible in the community. CONCLUSION: The
      WHI concurred with many other studies in finding that dietary fat intake is not a
      significant risk factor for CHD or breast cancer.

PMID- 16949144
TI  - Corrosion of nickel-based dental casting alloys.
AB  - OBJECTIVES: To study the microstructure, corrosion behaviour and cell culture
      response of two nickel-based dental casting alloys before and after a heat
      treatment to simulate porcelain firing. METHODS: The microstructure was studied
      using scanning electron microscopy (SEM) and energy dispersive X-ray analysis
      (EDX). Corrosion behaviour was evaluated by electrochemical measurements in
      artificial saliva at different values of pH in the presence of a crevice. 3T3
      mouse fibroblasts were exposed indirectly to alloy specimens and the number of
      viable cells counted after 3 and 6 days compared to a control culture. RESULTS:
      Small changes in microstructure were observed after heat treatment but had a
      negligible effect on the corrosion properties in the conditions tested. The alloy
      with a lower bulk level of Cr (12.6 wt.%) showed lower corrosion resistance,
      indicated by an increased passive current density and this stability was greatly
      reduced at pH 2.5, where crevice corrosion was observed. Selective dissolution
      occurred at regions within the microstructure containing lower levels of Cr and
      Mo. Furthermore, the proliferation of 3T3 mouse fibroblasts was reduced (p<0.05)
      when exposed indirectly to this alloy. The alloy containing a higher level of Cr
      (25 wt.%) showed superior corrosion resistance, which was associated with a more
      uniform distribution of Cr in the alloy microstructure. SIGNIFICANCE: The
      presence of crevices combined with an inhomogeneous distribution of Cr in the
      microstructure can lead to accelerated corrosion of Ni-based alloys with lower Cr
      contents. This effect can be avoided by increasing the Cr content of the alloy.

PMID- 16949143
TI  - Action and object processing in aphasia: from nouns and verbs to the effect of
      manipulability.
AB  - The processing of words and pictures representing actions and objects was tested
      in 21 aphasic patients and 20 healthy controls across three word production
      tasks: picture-naming (PN), single word reading (WR) and word repetition (WRP).
      Analysis 1 targeted task and lexical category (noun-verb), revealing worse
      performance on PN and verb items for both patients and control participants. For
      Analysis 2 we used data collected in a concurrent gesture norming study to re
      categorize the noun-verb items along hand imagery parameters (i.e., objects that
      can/cannot be manipulated and actions which do/do not involve fine hand
      movements). Here, patients displayed relative difficulty with the 'manipulable'
      items, while controls displayed the opposite pattern. Therefore, whereas the noun
      verb distinction resulted simply in lower verb accuracy across groups, the
      'manipulability' distinction revealed a 'double-dissociation' between patients
      and control participants. These results carry implications for theories of
      embodiment, lexico-semantic dissociations, and the organization of meaning in the
      brain.

PMID- 16949145
TI  - Material characteristics of a novel shrinkage-free ZrSiO(4) ceramic for the
      fabrication of posterior crowns.
AB  - OBJECTIVE: To confirm the clinical applicability of a novel ZrSiO(4) (zircon)
      based shrinkage-free ceramic material, the flexural strength, fracture toughness
      and chemical solubility were tested. In addition, the fracture load of full
      crowns made from this material was tested after cyclic thermomechanical loading.
      METHODS: Flexural strength of 12 specimens was measured using a biaxial bending
      test. Fracture toughness was measured using 10 slotted box shaped specimens. The
      specimens were fractured using a universal testing machine; fracture loads were
      recorded. A chemical solubility test was performed in accordance with ISO norm
      6872. Additionally, 32 ZrSiO(4) all-ceramic crowns were fabricated on extracted
      caries-free human molars. Sixteen Empress 2 and 16 PFM crowns served as a
      reference control. After artificial aging of 1.2 million cycles in the chewing
      simulator, the survival rate of the crowns was determined. The fracture load of
      all surviving specimens was obtained by loading the crowns until fracture in a
      universal testing machine. RESULTS: A flexural strength of 328MPa was found. The
      fracture toughness of the ZrSiO(4) ceramic was 5.16MPam(0.5). The chemical
      solubility amounted to 7.2microg/cm(2). All specimens survived the chewing
      simulation (survival rate: 100%); no crowns had to be re-cemented. A mean
      fracture strength of 1790N was found for Everest HPC for Empress 2 crowns, 1715N
      for Empress 2 crowns and 2416N for PFM crowns. Fracture loads of PFM crowns were
      significantly higher than for Empress 2 crowns (P=0.032) as well as ZrSiO(4)
      crowns (P=0.007). There was no significant difference between ZrSiO(4)-crowns and
      Empress 2 crowns (P=0.743). SIGNIFICANCE: At the present stage, Everest HPC can
      be recommended for the fabrication of single crowns as an alternative to
      conventional PFM and other all-ceramic crowns, because its fracture strength
      exceeds average masticatory forces in the posterior region.

PMID- 16949146
TI  - Monomer conversion and hardness of novel dental cements based on ethyl
      cyanoacrylate.
AB  - OBJECTIVES: The aim of this work was to study the setting of two novel dental
      cements: (i) a 'hybrid' cement, incorporating an ethyl cyanoacrylate into a glass
      ionomer cement (ECGIC) formulation and (ii) an ethyl cyanoacrylate/hydroxyapatite
      composite cement (ECHC). The mechanical role of the cyanoacrylate and its curing
      within the cements have been discussed. METHODS: The setting of the cements was
      characterised using Vickers indentation hardness and near-infrared (near-IR)
      spectroscopy. RESULTS: The cyanoacrylate component of ECGIC was 100% cured
      approximately 10min after the initial cement mixing. The ECGIC continued to
      increase in hardness after the cyanoacrylate component was fully cured. This
      proved that the fully polymerised network of cyanoacrylate did not prevent the
      acid-base reactions of the GIC components from continuing. The Vickers hardness
      number of ECGIC at 18 weeks was approximately 105. The curing of the
      cyanoacrylate within ECHC was much slower and was still not complete (98%) 18
      weeks after the initial cement mixing. The hardness of the ECHC was shown to be
      correlated with the extent of cyanoacrylate cure. The Vickers hardness number of
      ECHC at 18 weeks was approximately 21. The primary reasons for the overall lower
      hardness of ECHC in comparison to ECGIC were the lower powder:liquid ratio and
      the softer filler type. SIGNIFICANCE: Careful consideration is needed when
      incorporating cyanoacrylates into dental cements, as speed of cure and hardness
      are particularly important.

PMID- 16949147
TI  - Stability and reactivity of acid phosphatase immobilized on composite beads of
      chitosan and ZrO2 powders.
AB  - Equal weights of chitosan and ZrO2 powders were mixed in acetic acid solution to
      prepare the composite beads. They were then cross-linked with glutaraldehyde and
      stored with and without freeze-drying before use. The physicochemical properties
      of acid phosphatase immobilized on four types of the supports (wet/dried pure
      chitosan beads, wet/dried chitosan-ZrO2 composite beads) were compared. Various
      parameters including glutaraldehyde concentration, cross-linking time, enzyme
      concentration, temperature, and pH on enzyme activity were studied. It was shown
      that the activity yield of enzyme immobilized on the dried chitosan-ZrO2 beads
      was the highest, and the relative activity remained above 83.2% within pH 2.9
      5.8. Regardless of wet or dried beads, the Michaelis constant KM and maximum rate
      of reaction Vmax of acid phosphatase immobilized on chitosan-ZrO2 composite beads
      were 1.8 times larger than those on pure chitosan beads. Of the four immobilized
      enzymes, the use of wet chitosan-ZrO2 bead as the support showed the lowest
      thermal deactivation energy (78 kJ mol(-1)).

PMID- 16949148
TI  - In vitro biocompatibility of electrospun poly(3-hydroxybutyrate) and poly(3
      hydroxybutyrate-co-3-hydroxyvalerate) fiber mats.
AB  - In the present contribution, the potential for use of the ultrafine electrospun
      fiber mats of poly(3-hydroxybutyrate) (PHB) and poly(3-hydroxybutyrate-co-3
      hydroxyvalerate) (PHBV) as scaffolding materials for skin and nerve regeneration
      was evaluated in vitro using mouse fibroblasts (L929) and Schwann cells (RT4
      D6P2T) as reference cell lines. Comparison was made with PHB and PHBV films that
      were prepared by solution-casting technique. Indirect cytotoxicity assessment of
      the as-spun PHB and PHBV fiber mats with mouse fibroblasts (L929) and Schwann
      cells (RT4-D6P2T) indicated that the materials were acceptable to both types of
      cells. The attachment of L929 on all of the fibrous scaffolds was significantly
      better than that on both the film scaffolds and tissue-culture polystyrene plate
      (TCPS), while RT4-D6P2T appeared to attach on the flat surfaces of TCPS and the
      film scaffolds much better than on the rough surfaces of the fibrous scaffolds.
      For L929, all of the fibrous scaffolds were superior in supporting the cell
      proliferation to the film counterparts, but inferior to TCPS at days 3 and 5,
      while, for RT4-D6P2T, the rough surfaces of the fibrous scaffolds appeared to be
      very poor in supporting the cell proliferation when comparing with the smooth
      surfaces of TCPS and the film scaffolds. Scanning electron microscopy was also
      used to observe the behavior of both types of cells that were cultured on both
      the fibrous and the film scaffolds and glass substrate for 24 h.

PMID- 16949149
TI  - Poly(gamma,L-glutamic acid)-cisplatin conjugate effectively inhibits human breast
      tumor xenografted in nude mice.
AB  - An easily administered cis-dichlorodiammineplatinum (II) (CDDP) formulation with
      less toxicity and greater antitumor effect would be extremely valuable. We
      describe PGA-CDDP, a water-soluble CDDP derivative. The hydrolyzed gamma-PGA has
      a molecular weight between 45 and 60 kDa, and is a water-soluble, biodegradable,
      and nontoxic polymer produced by microbial fermentation. CDDP can be released
      from the resulting conjugate in PBS: there was initially a burst release during
      the first 6h, followed by sustained release. In vitro, PGA-CDDP was less potent
      than free CDDP at inhibiting cell growth in the Bcap-37 cell line. PGA-CDDP was
      given as 3 doses at an equivalent CDDP dose of 4 or 12 mg/kg with 2-day intervals
      between injections to Bcap-37-grafted mice. This treatment showed stronger
      antitumor activity and was less toxic than CDDP in vivo. Antitumor activity
      assays demonstrated that the PGA-CDDP conjugate treatment had significantly
      higher antitumor activity than control PBS treatment (P<0.01). PGA-CDDP also
      increased the survival of mice bearing Bcap-37 cells with reference to PBS
      treatment or free CDDP treatment. Furthermore, mice treated with PGA-CDDP (4
      mg/kg, administered on day 0 and 5) showed no body weight loss (P>0.05 with
      respect to PBS treatment), whereas free CDDP treatment at the same dose caused a
      body weight loss of 20-30% (P<0.001). These findings suggest that PGA produced by
      microbial fermentation may be used as an effective drug carrier for CDDP and that
      PGA-CDDP may have potential applications in the treatment of human breast cancer.

PMID- 16949150
TI  - A quantitative method for evaluating the degradation of biologic scaffold
      materials.
AB  - Scaffolds derived from naturally occurring extracellular matrix (ECM) have found
      extensive use in the fields of tissue engineering and regenerative medicine. Many
      of these scaffolds are designed to degrade rapidly as they are replaced by new
      host tissue. Other scaffolds are chemically crosslinked to slow the rate of
      degradation or add strength to the scaffold. Commercially available ECM scaffolds
      have considerable variability with regards to tissue origin and methods of
      processing, and little is known about their rate of degradation and the fate of
      their degradation products. A novel method is described herein to integrally
      label ECM with a radioactive isotope ((14)C). It was found that a number of
      tissues are efficiently labeled, including heart, liver, trachea, pancreas, small
      intestine, and urinary bladder tissue. Of the tissues analyzed, only spleen was
      not found to contain detectable levels of (14)C. The technique is extremely
      sensitive, accurate, and safe, but requires access to accelerator mass
      spectrometry, and is expensive and time consuming. This model represents the
      first described quantitative method to determine the rate of degradation for an
      ECM scaffold and to track the fate of the degradation products.

PMID- 16949151
TI  - Effects of orthopaedic wear particles on osteoprogenitor cells.
AB  - Wear particles from total joint arthroplasties are constantly being generated
      throughout the lifetime of an implant. Since mesenchymal stem cells and
      osteoprogenitors from the bone marrow are the precursors of osteoblasts, the
      reaction of these cells to orthopaedic wear particles is critical to both initial
      osseointegration of implants and ongoing regeneration of the periprosthetic bed.
      Particles less than 5 microm can undergo phagocytosis by mature osteoblasts, with
      potential adverse effects on cellular viability, proliferation and function. The
      specific effects are dependent on particle composition and dose. Metal and
      polymer particles in non-toxic doses stimulate pro-inflammatory factor release
      more than ceramic particles of a similar size. The released factors inhibit
      markers of bone formation and are capable of stimulating osteoclast-mediated bone
      resorption. Mesenchymal stem cells and osteoprogenitors are also profoundly
      affected by wear particles. Titanium and polymethylmethacrylate particles inhibit
      bone cell viability and proliferation, and downregulate markers of bone formation
      in a dose- and time-dependent manner. Future studies should delineate the
      molecular mechanisms by which particles adversely affect mesenchymal stems cells
      and the bone cell lineage and provide strategies to modulate these effects.

PMID- 16949152
TI  - Many cold sensitive peripheral neurons of the mouse do not express TRPM8 or
      TRPA1.
AB  - Neurons of the peripheral nervous system detect changes in temperature through
      activation of specialised ion channels. Members of the transient receptor
      potential family TRPM8 and TRPA1 are candidates for the principal transducers of
      cold stimuli. Using ratiometric calcium imaging we now show that 19% of acutely
      dissociated mouse dorsal root (DRG) and 45% of superior cervical ganglia (SCG)
      neurons responded to a brief cold stimulus. Amongst cold-responsive DRG neurons
      34+/-2% responded to the TRPM8 agonist menthol, 18+/-3% to the TRPA1 agonist
      mustard oil and 5% to both stimuli. A third of the cold-sensitive neurons did not
      respond to any TRP channel agonist. Cold-sensitive neurons of the SCG did not
      respond to menthol and only 3% responded to mustard oil. The threshold of SCG
      neurons was at significantly cooler temperatures than that of DRG neurons. Using
      real-time PCR, TRPA1 was expressed over 100-fold more in DRG than SCG, while
      TRPM8 was present in DRG only. The relatively small amount of TRPA1 transcript
      present in SCG did not correlate with the high level of cold sensitivity. We
      conclude that cold sensitivity in sympathetic neurons and in a significant
      proportion of sensory neurons is generated in the absence of TRPM8 and TRPA1.

PMID- 16949153
TI  - Four novel point mutations in exons 12, 13, and 14 of the FLT3 gene.

PMID- 16949154
TI  - The changes of oxidative stress and human 8-hydroxyguanine glycosylase1 gene
      expression in depressive patients with acute leukemia.
AB  - The results of several recent studies indicated that free radicals are involved
      in the biochemical mechanisms that underlie neuropsychiatric disorders. In the
      present study, we evaluated changes in oxidative stress and human 8
      hydroxyguanine glycosylase1 gene (hOGG1) expression in depressive patients with
      acute leukemia. Ninety two cases were assessed using the Zung self-rating
      depression scale (SDS) and multiple-item questionnaires. We measured total
      antioxidant capacity (T-AOC) and the concentrations of reactive oxygen species
      (ROS), superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO)
      during a pre-treatment period. The steady-state expression of hOGG1 mRNA
      transcripts was monitored. The incidence of depression was 47.83%. There was a
      significant decrease in serum T-AOC and SOD concentrations in depressive patients
      compared to the control subjects, whereas the opposite was the case for serum
      concentrations of ROS, NO and MDA. Real-time polymerase chain reaction (PCR)
      revealed that hOGG1 mRNA expression was greater in depressive patients than in
      the controls. Person correlation analysis revealed that depression was correlated
      positively with sex, the course of the disease and hOGG1 mRNA expression;
      depression was correlated negatively with T-AOC. Based on these results, we
      conclude that the antioxidant system is impaired in leukemic patients with
      affective disorders. Therefore, oxidative stress may play an important role in
      the pathophysiology of depression.

PMID- 16949155
TI  - Genetic variations in benzene metabolism and susceptibility to multiple myeloma.
AB  - We have previously shown that deficiency in the biotransformation enzyme
      glutathione-S-transferase theta (GSTT1) is a risk factor for multiple myeloma
      (MM). The present case-control study of 102 MM patients and 205 controls revealed
      a significant trend in increasing risk of MM with inheritance of multiple
      putative 'high risk' genetic variants in related pathways of benzene
      detoxification. Individuals who carried polymorphisms for GSTT1 null and/or high
      activity microsomal epoxide hydrolase (mEH 113YY+139HR or 113YY+139RR or
      113YH+139RR) and/or low activity NAD(P)H:quinone oxidoreductase 1 (NQO1 187PS/SS)
      were 1.65, 2.49 and 13 times more likely to have MM (P(trend)=0.001).

PMID- 16949156
TI  - Characterization of a Rel?NF-kappaB homologue in a gastropod abalone, Haliotis
      diversicolor supertexta.
AB  - Rel?NF-kappaB signal transduction pathway is evolutionarily conserved and
      involved in numerous biological processes. We report here, for the first time
      that a homologue of Rel?NF-kappaB transcription factor, Ab-Rel, was identified
      and functionally characterized in a gastropod abalone, H. diversicolor
      supertexta. The full-length Ab-Rel cDNA consists of 1943 bp with an ORF encoding
      a 584 amino acids protein. Amino acid sequence analysis revealed that Ab-Rel
      shares conserved signature motifs with other Rel proteins, including the Rel
      homology domain (RHD), nuclear localization signal (NLS) and phosphorylation
      site, RRPS. Northern hybridization and real-time PCR indicated that Ab-Rel was
      ubiquitously and constitutively expressed in abalone. The recombinant Ab-Rel RHD
      protein was confirmed to specifically bind the consensus NF-kappaB binding site.
      Furthermore, EMSA showed that NF-kappaB activity was induced in abalone hemocytes
      by stimulation with LPS. These results strongly suggest that Ab-Rel is a Rel
      homologue, which plays a conserved role in the immune response of the ancient
      invertebrate, abalone, allowing us to study the Rel?NF-kappaB signaling pathway
      in an evolutionary context.

PMID- 16949157
TI  - Darwin's young admirers.
AB  - In 1873, Darwin replied to the second letter from a young Dutch admirer, Nicolaas
      Doedes, in which he had eagerly asked about Darwin's religious views. Darwin
      stated that he could not believe that "this grand and wondrous universe" had only
      arisen by chance, but also showed his doubts about the existence of God. In 1881,
      Darwin repeated a similar agnostic view. After the death of Darwin in 1882,
      Doedes incurred the wrath of Francis Darwin by publishing the confession of his
      father in a Dutch freethinking journal, thus revealing the sensitivity of the
      information Darwin shared with Doedes.

PMID- 16949158
TI  - Iodine 125 plaque radiotherapy as salvage treatment for retinoblastoma recurrence
      after chemoreduction in 84 tumors.
AB  - PURPOSE: To assess tumor control and complications of iodine 125 (I125) plaque
      radiotherapy for retinoblastoma recurrence after chemoreduction (CRD). DESIGN:
      Interventional retrospective case series. PARTICIPANTS: Children with
      retinoblastoma treated on the Oncology Service, Wills Eye Hospital, initially
      examined from July 1994 to April 2005. METHODS: Eighty-four retinoblastomas with
      solid recurrence after CRD were treated with custom designed I125 plaque
      radiotherapy. Eyes with vitreous or subretinal seed recurrence were excluded. The
      CRD regimen included vincristine, etoposide, and carboplatin for 6 cycles plus
      local consolidation with thermotherapy or cryotherapy. The only alternatives to
      plaque radiotherapy in these cases would have been external beam radiotherapy
      (EBRT), additional chemotherapy, or enucleation. MAIN OUTCOME MEASURES: Tumor
      control and radiation complications. RESULTS: Tumor control was achieved in 95%
      of eyes by 5 years follow-up. Of the 59 recurrent tumors after CRD alone, 56
      (95%) were controlled with plaque radiotherapy. Of the 25 recurrent tumors after
      CRD and EBRT, 100% were controlled with plaque radiotherapy. Of the 3 failures
      after plaque radiotherapy, the median time to failure (tumor recurrence) was 4
      months and all recurrences were detected within 1 year. There were no
      identifiable factors predictive of plaque radiotherapy failure. Using Kaplan
      Meier analysis, radiation complications at 5 years included proliferative
      retinopathy (19%), nonproliferative maculopathy (24%), papillopathy (16%),
      transient mild vitreous hemorrhage (54%), cataract (43%), iris neovascularization
      (NVI; 8%), and glaucoma (4%). Nonresolving vitreous hemorrhage and scleral
      necrosis did not occur. Radiation complications showed minimal change at 10 and
      15 years of follow-up. CONCLUSIONS: Iodine 125 plaque radiotherapy offers 95%
      tumor control for selected retinoblastomas that fail CRD. Complications such as
      radiation retinopathy and mild vitreous hemorrhage should be anticipated,
      depending on the location, size, and extent of the tumor.

PMID- 16949159
TI  - Stable bellows cup electrode demonstrates low-frequency properties of long-term
      electroretinographic recordings in the Limulus lateral eye.
AB  - Conventional methods have long been used to record electroretinograms (ERGs) from
      the surface of the lateral eye of Limulus, the horseshoe crab. But, using these
      methods, the convexity of this eye has sometimes led to electrode problems that
      deterred acceptance of the validity of unexpected and unfamiliar phenomena. To
      deal with the electrode problem, a new gel/bellows cup electrode has been devised
      which was created from a small bellows suction cup. Coated with a recording gel
      and positioned by a massive apparatus arrangement, it maintains a secure
      connection to the convexity of the lateral eye for many days without requiring
      any attention after its placement. This new electrode has now been used for
      thousands of hours of ERG research during which crabs have often been left
      undisturbed in the apparatus for many days. This new method has revealed the
      existence of a novel low-frequency phenomenon demonstrated by the occurrence of
      noise-like fluctuations in successive ERGs. The frequency of these fluctuations
      is low relative to the properties of the ERG itself. Several converging tests of
      this new electrode system indicated that this new phenomenon is not an artifact
      but rather a genuine expression of endogenous bioelectric events.

PMID- 16949160
TI  - Suitability of the TEMPS-A for population-based studies: ease of administration
      and stability of affective temperaments in its Lebanese version.
AB  - BACKGROUND: The Temperament Evaluation of Memphis Pisa Paris and San Diego Auto
      questionnaire (TEMPS-A) has been translated and validated into several languages,
      and used in different subgroups (e.g. clinical, students, company, employees and
      those with different educational levels). METHODS: Lebanon is the only country
      that has validated the TEMPS-A in a national cohort, as part of the Lebanese
      Evaluation of the Burden of Ailments and Needs Of the Nation (LEBANON). In this
      paper, we test the suitability of the TEMPS-A for large scale epidemiologic
      population-based studies. RESULTS: 82.1% of the respondents found the TEMPS-A to
      be easy to understand. The global reports of the Lebanese of their own
      temperaments paralleled those of the formal sub-scores on the five affective
      temperament subscales. The majority of respondents (90.3%) felt that their
      answers on the Lebanese-Arabic TEMPS-A scale represented them throughout their
      adulthood; the minority who did not were more likely to be older, and to have
      scored higher on the cyclothymic, and lower on the hyperthymic subscales.
      LIMITATION: Although the TEMPS-A has been designed for self-administration (auto
      questionnaire), this was not practical in all subjects. We nonetheless feel that
      the interview format is viable as it introduces flexibility with certain subjects
      in population studies. CONCLUSIONS: The TEMPS-A appears to be suitable for use in
      epidemiologic surveys and research.

PMID- 16949161
TI  - Is bipolar II disorder misdiagnosed as major depressive disorder in children?
AB  - OBJECTIVES: To estimate the lifetime prevalence of bipolar II disorder in
      children and adolescents presenting with DSM-IV major depressive disorder (MDD).
      METHODS: Sixty-one consecutive subjects aged < or =18 years attending the
      outpatient services of the Child and Adolescent Psychiatric (CAP) services of the
      National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India
      with a diagnosis of MDD were evaluated using the Missouri Assessment of Genetics
      Interview for children (MAGIC). Two psychiatrists, one of whom was a child
      psychiatrist diagnosed hypomania by consensus. RESULTS: Twelve children had a
      past episode of hypomania (20%), which was hitherto undiagnosed clinically.
      LIMITATIONS: We recruited subjects from a psychiatric hospital, thus limiting the
      generalizability of the finding. Sample size was relatively small and assessments
      were cross-sectional. CONCLUSIONS: : Our study shows that bipolar II disorder is
      often misdiagnosed as MDD in children. The study also highlights that the chance
      of diagnosing bipolarity is enhanced by using semi-structured interview in
      routine clinical practice.

PMID- 16949162
TI  - Evaluation of the effect of acetochlor on thyroid hormone receptor gene
      expression in the brain and behavior of Rana catesbeiana tadpoles.
AB  - The thyroid hormones (THs) including 3,5,3'-triiodothyronine (T3), are important
      regulators of growth and development of the brain in vertebrates. Previous
      studies showed that acetochlor, a widely used herbicide, accelerates T3 -induced
      frog tadpole metamorphosis and elevates the T3 -dependent accumulation of the
      mRNAs encoding the TH receptors, TRalpha and beta, in the tail. Here we show that
      acetochlor affects the expression of these TR isoforms in the brain of Rana
      catesbeiana tadpoles. Premetamorphic tadpoles exposed to 10 nM acetochlor with
      and without 100 nM T(3) for 4 days showed substantial increases in TRalpha and
      TRbeta transcript levels and significant decreases in the TRalpha/TRbeta ratios
      in their brains. This change in TR ratios is recapitulated with 10 nM acetochlor
      in R. catesbeiana tadpole brains during prometamorphosis, a period in which THs
      are endogenously produced. Tail fin biopsies revealed an elevation in TRalpha and
      beta mRNA levels compared to control animals when exposed to 1 and 10 nM
      acetochlor for 6 days. When subsequently reared in clean water for 59 days, no
      alterations in metamorphic hallmarks (forelimb emergence, mouth development, tail
      regression) were noted compared to the controls. Since alterations in TR
      ratios/levels may impact brain development, we tested the escape behavior in
      premetamorphic tadpoles exposed to 10 nM acetochlor for 4 days. We did not detect
      any statistically significant differences that would indicate that acetochlor
      affects escape behavior. However, since the gene expression data suggest that
      brain function may be affected, additional studies examining different behaviors
      upon acetochlor exposure at environmentally-relevant concentrations are
      warranted.

PMID- 16949163
TI  - CYP1A-immunopositive proteins in bivalves identified as cytoskeletal and major
      vault proteins.
AB  - To identify possible CYP1A-immunopositive proteins in bivalves, we used anti-fish
      CYP1A antibodies combined with one- and two-dimensional gel electrophoresis and
      mass spectrometry, and found that two of the main CYP1A-immunopositive proteins
      in digestive gland of Mytilus edulis, were cytoskeletal actin (42 kDa) and major
      vault protein (102 kDa), while the main CYP1A-immunopositive protein in the clam
      Chamaelea gallina was the cytoskeletal protein tropomyosin (33 kDa). Anti-CYP1A
      cross-reactive bands of 48-54 and 75 kDa in M. edulis were observed but not
      identified in this study. Sequence alignments with one of the most conserved
      CYP1A regions (NIRDITDSLIDHCED) from fish revealed similarities with tropomyosin
      and actin sequences from mussels, which could explain the immunological cross
      reactivity. Changes in isoforms of tropomyosin after exposure to Aroclor1254 and
      Cu(II), could indicate modifications due to oxidative stress. Effects of
      pollutant related oxidative stress on the cytoskeleton require further studies.

PMID- 16949164
TI  - Phosphoproteomic profiling of human SH-SY5Y neuroblastoma cells during response
      to 6-hydroxydopamine-induced oxidative stress.
AB  - Dopaminergic neurons are known to be vulnerable to age-related neuronal disorders
      due to reactive oxygen species (ROS) generated during dopamine metabolism.
      However, it remains unclear what kinds of proteins are involved in the response
      to oxidative stress. We examined changes in whole proteins and phosphoproteins in
      the human dopaminergic neuroblastoma cell line SH-SY5Y under oxidative stress
      induced by the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA). Proteins of SH
      SY5Y cells at various stages of oxidative stress were separated by two
      dimensional gel electrophoresis for comparative analysis. Increase in glutathione
      S-transferase pi was detected on SYPRO Ruby-stained gels by computer-aided image
      analysis. Stress-induced alterations in phosphoproteins were detected by Pro-Q
      Diamond staining. Elongation factor 2, lamin A/C, T-complex protein 1, and
      heterogeneous nuclear ribonucleoprotein H3 were identified by MALDI-TOF mass
      spectrometry as stress-responsive elements.

PMID- 16949165
TI  - Role of p120-catenin in cadherin trafficking.
AB  - p120-catenin (p120) has emerged over the past several years as an important
      regulatory component of the cadherin adhesive complex. A core function of p120 in
      mammalian cells is to stabilize cadherins at the cell membrane by modulating
      cadherin membrane trafficking and degradation. In this way, p120 levels act as a
      set point mechanism that tunes cell-cell adhesive interactions. The primary
      control point for this regulatory activity appears to be at the level of cadherin
      internalization from the plasma membrane, although p120 may also impact other
      aspects of cadherin trafficking and turnover. In the following review, the
      general mechanisms of cadherin trafficking are discussed, and models for how p120
      may influence cadherin membrane dynamics are presented. In one model, p120 may
      function as a "cap" to bind the cadherin cytoplasmic tail and prevent cadherin
      interactions with endocytic membrane trafficking machinery. Alternatively, p120
      may stabilize cell junctions or regulate membrane trafficking machinery through
      interactions with small GTPases such as Rho A, Rac and Cdc42. Through these
      mechanisms p120 exerts influence over a wide range of biological processes that
      are dependent upon tight regulation of cell surface cadherin levels.

PMID- 16949166
TI  - The biochemistry of oleate induction: transcriptional upregulation and peroxisome
      proliferation.
AB  - Unicellular organisms such as yeast constantly monitor their environment and
      respond to nutritional cues. Rapid adaptation to ambient changes may include
      modification and degradation of proteins; alterations in mRNA stability; and
      differential rates of translation. However, for a more prolonged response,
      changes are initiated in the expression of genes involved in the utilization of
      energy sources whose availability constantly fluctuates. For example, in the
      presence of oleic acid as a sole carbon source, yeast cells induce the expression
      of a discrete set of enzymes for fatty acid beta-oxidation as well as proteins
      involved in the expansion of the peroxisomal compartment containing this process.
      In this review chapter, we discuss the factors regulating oleate induction in
      Saccharomyces cerevisiae, and we also deal with peroxisome proliferation in other
      organisms, briefly mentioning fatty acid-independent signals that can trigger
      this process.

PMID- 16949167
TI  - Nutritional status and clinical outcomes among institutionalized elderly Chinese
      in Taiwan.
AB  - Nutrition is an important issue in institutional care, and is related to clinical
      outcomes in many aspects. Although Taiwan is marching to an aged society, related
      studies were lacking. Elderly residents in two long-term care facilities (LTCF)
      were enrolled for study. Nutritional status including anthropometric measurements
      and laboratory examinations was assessed every 3 months for 12 months. Age, sex
      matched community-dwelling elderly participating in the annual health check-up
      was randomly selected as the control subjects. In total, 66 subjects in LTCF and
      870 age, sex-matched community-dwelling elderly were enrolled. Body mass index,
      serum levels of albumin, and total cholesterol were significantly poorer in LTCF
      residents than the community-dwelling elderly. Triceps skinfold thickness,
      hemoglobin, serum albumin, and total cholesterol were progressively deteriorated
      among the institutionalized elderly during the 6-month follow-up. Thirteen
      subjects of the study group had been hospitalized during the follow-up. Body mass
      index, triceps skinfold thickness, mid-arm circumference, serum albumin at
      screening were significantly poorer and unintentional weight loss within 6 months
      was significantly greater in subjects who had been hospitalized. By using
      multivariate logistic regression model, only weight loss >5% within 6-month
      follow-up was the significant independent predictive factors to hospitalization.
      In conclusion, nutritional status of institutionalized elderly Chinese was
      significantly poorer than the community-dwelling elderly. Nutritional markers
      were progressively deteriorated in LTCF residents during the follow-up period.
      Unintentional weight loss >5% within 6 months was the only significantly
      independent predictive factor for hospitalization among the institutionalized
      elderly Chinese.

PMID- 16949168
TI  - Effect of Neospora caninum-serostatus on culling, reproductive performance and
      milk production in Dutch dairy herds with and without a history of Neospora
      caninum-associated abortion epidemics.
AB  - We quantified the effect of Neospora caninum (NC)-serostatus on culling and
      (re)production in 83 herds randomly selected from the Dutch dairy herd population
      (random group) and in 17 herds that had experienced an abortion epidemic
      associated with NC infection (epidemic-abortion group). In the random group, a
      single whole-herd blood sampling was done during the spring of 2003, while in the
      epidemic-abortion group whole-herd blood sampling was done repeatedly at least
      once a year starting after the abortion epidemic during the period 1997-2000
      until the summer of 2004. Serological test-results for NC were given as
      'negative' (N), 'low-positive' (LP) and 'high-positive' (HP). For analysing the
      time to culling, calving interval and age of first calving, survival analysis was
      used. For categorical reproduction parameters either a logistic-regression model
      (abortion, non-return after 1st insemination) or a Poisson-regression model
      (number of inseminations per pregnancy) was used. For milk production a linear
      mixed model was used. All models were controlled, if applicable, for confounding
      variables like parity, production, season, year and abortion and adjusted for
      within-herd clustering. In random herds, HP serostatus increased the hazard for
      culling 1.73-fold (95% CI: 1.37-2.19) compared to N and LP serostatus. Compared
      to N serostatus, LP and HP serostatus in epidemic-abortion herds increased the
      odds for abortion 1.88-fold (95% CI: 1.41-2.52) and 1.72-fold (95% CI: 1.38
      2.14), respectively. No other reproduction parameters were associated with NC
      serostatus in the random or epidemic-abortion herds. We found no effect of
      serostatus on milk production in the random group. In contrast, milk production
      of LP and HP serostatus in the epidemic-abortion group was respectively,
      0.72kgmilk/day (95% CI: 0.15-1.03) and 0.59kgmilk/day (95% CI: 0.13-1.30), less
      during the first 100 days of lactation in the first year after the abortion
      epidemic compared with N serostatus.

PMID- 16949169
TI  - Omission of elective node irradiation on basis of CT-scans in patients with
      limited disease small cell lung cancer: a phase II trial.
AB  - PURPOSE: To evaluate the patterns of recurrence when elective node irradiation
      was omitted in patients with limited disease small cell lung cancer (LD-SCLC).
      METHODS: A prospective phase II study was undertaken in 27 patients with LD-SCLC
      without detectable distant metastases on CT scan. Chest radiotherapy to a dose of
      45 Gy in 30 fractions in 3 weeks (1.5 Gy BID with 6 - 8 h interval) was delivered
      concurrently with carboplatin and etoposide chemotherapy. Chest radiation started
      after a mean time of 17.7 days +/- 9.7 days (SD) (range: 0-33 days) after the
      beginning of chemotherapy. Only the primary tumour and the positive nodal areas
      on the pre-treatment CT scan were irradiated. A total of five chemotherapy cycles
      were administered, followed by prophylactic cranial irradiation (PCI) in patients
      without disease progression. Isolated nodal failure was defined as recurrence in
      the regional nodes outside of the clinical target volume, in the absence of in
      field failure. RESULTS: After a median time of 18 months post-radiotherapy, 7
      patients (26%, 95% CI 19.5-42.5%) developed a local recurrence. Three patients
      (crude rate 11%, 95% CI 2.4-29%), developed an isolated nodal failure, all of
      them in the ipsilateral supraclavicular fossa. The median actuarial overall
      survival was 21 months (95% CI 15.3-26.7), and the median actuarial progression
      free survival was 16 months (95% CI 6.5-25.5). Eight patients developed an acute,
      reversible grade 3 (CTC 3.0) radiation oesophagitis (30%, 95% CI 14-50%).
      CONCLUSIONS: Because of the small sample size, no definitive conclusions can be
      drawn. However, the omission of elective nodal irradiation on the basis of CT
      scans in patients with LD-SCLC resulted in a higher than expected rate of
      isolated nodal failures in the ipsilateral supraclavicular fossa. The incidence
      of acute, reversible oesophagitis was in the same range as reported with elective
      nodal fields. The safety of selective nodal irradiation in NSCLC should not be
      extrapolated to patients with LD-SCLC until more data are available. In the mean
      time, elective nodal irradiation should only be omitted in clinical trials.

PMID- 16949170
TI  - Stress induces the expression of heterotrimeric G protein beta subunits and the
      phosphorylation of PKB/Akt and ERK1/2 in rat brain.
AB  - Various heterotrimeric G protein betagamma subunits (Gbetagamma) are region
      specifically expressed in brain where associated with "stress-axis", however, the
      role of Gbetagamma-mediated signaling in regulating stress is unknown. This study
      was designed to examine the changes of Gbetagamma expression and Gbetagamma
      mediated signaling in rat brain by stress. Experimental stress was induced by
      immobilization (2h/day for 7 days) and the level of mRNAs and proteins for
      Gbeta(1-5), and the phosphorylation of PKB/Akt (phosphatidylinositol 3-kinase
      linked protein kinase B) and ERK1/2 (extracellular signal-regulated kinase 1/2)
      were measured in five different regions of rat brain including frontal cortex,
      striatum, hypothalamus, hippocampus, and cerebellum. As compared in not-handled
      non-stressed animals, the expression of both mRNAs and proteins for Gbeta(1-5) in
      brain regions associated with stress was increased in stressed animals.
      Especially, a significant increase in Gbetas immunoreactivity in the caudate
      putamen, the paraventricular nucleus of the hypothalamus (PVN), and the dentate
      gyrus of the hippocampus (DG) of stressed rats was observed. Stress significantly
      induced the phosphorylation of PKB/Akt and ERK1/2 in striatum, hypothalamus and
      hippocampus. Therefore, these results suggest that stress may activate, at least
      in part, the Gbetagamma-mediated PKB/Akt and ERK1/2 signaling pathway by
      increasing the expression of Gbetas to regulate the physiological responses.

PMID- 16949171
TI  - Use of routine beef carcase Escherichia coli monitoring data to investigate the
      relationship between hygiene status of incoming stock and processing efficacy.
AB  - In Australian export-registered abattoirs microbiological monitoring is carried
      out within the E. coli and Salmonella Monitoring (ESAM) program. During the
      calendar year 2003, the ESAM database indicated a national prevalence of
      Escherichia coli of around 3.0% for steers/heifers and 7.1% for cows/bulls. An
      investigation was carried out to attempt to elucidate why some establishments had
      E. coli prevalence markedly higher or markedly lower than the national average.
      The investigation was based on a questionnaire completed by fifteen export
      establishments which provided data on livestock, processing, operator training
      and management. The responses were verified by site visits and then evaluated for
      their relationship with ESAM data on E. coli in two stages. In stage 1, E. coli
      prevalence for each abattoir was plotted against each variable recorded by the
      questionnaire; no single variable was a reasonable predictor for prevalence of E.
      coli on carcases. In stage 2, variables influencing contamination were grouped
      under two categories: contamination on incoming livestock (Problem variables)
      together with the ability of the plant's process to deal with such contamination
      (Process variables). The analysis prompted two main conclusions. Firstly, plants
      with a large incoming problem with livestock (long haul, high tag score and
      proportion of cows/bulls slaughtered) plus "poor" processes had higher than
      average E. coli prevalence. Secondly, plants with hot water decontamination
      systems had low E. coli prevalence even when there was a substantial incoming
      problem with livestock, such as a relatively high proportion of cows/bulls.

PMID- 16949172
TI  - Effect of bacterial interactions on the spoilage of cold-smoked salmon.
AB  - Cold-smoked salmon is a lightly preserved fish product in which a mixed microbial
      flora develops during storage and where the interactive behaviour of micro
      organisms may contribute to their growth and spoilage activity. The aim of this
      study was to assess the effect of the bacterial interactions between the main
      species contaminating the cold-smoked salmon on bacterial growth, chemical and
      sensory changes, and spoilage. First, Carnobacterium piscicola, Photobacterium
      phosphoreum, Lactobacillus sakei, Vibrio sp., Brochothrix thermosphacta and
      Serratia liquefaciens-like were inoculated as pure cultures on sterile cold
      smoked salmon. All bacterial species grew well; Vibrio sp. was the fastest and L.
      sakei strains developed very rapidly as well with a high maximum cell density on
      cold-smoked salmon blocks (up to 10(9) cfu g(-1) after 10 days at 8 degrees C).
      Based on sensory analysis, Vibrio sp. was identified as non-spoilage bacteria, C.
      piscicola as very lightly and B. thermosphacta as lightly spoiling. L. sakei and
      S. liquefaciens-like were found to be the most spoiling bacteria. Secondly, C.
      piscicola and L. sakei, two species frequently occurring in the lactic flora of
      the product, were inoculated together and each of them in mixed cultures with
      respectively P. phosphoreum, Vibrio sp., B. thermosphacta, and S. liquefaciens
      like. The growth of L. sakei was shown to strongly inhibit most of the co
      inoculated strains i.e. P. phosphoreum, B. thermosphacta, S. liquefaciens-like
      and, to a lesser extent, Vibrio sp. The growth of C. piscicola seemed to be
      enhanced with B. thermosphacta and to develop earlier with P. phosphoreum and
      Vibrio sp. Conversely, S. liquefaciens-like and P. phosphoreum were weakly
      inhibited by C. piscicola. The main observation resulting from the sensory
      evaluation was the delay in the appearance of the spoilage characteristics in the
      mixed cultures with L. sakei, in particular L. sakei/ S. liquefaciens-like. On
      the other hand, the spoilage activity of the non-spoiler strains Vibrio sp. or
      the moderate spoilage strains B. thermosphacta and C. piscicola was increased
      when they were associated together. It is concluded that the spoilage behaviour
      of micro-organisms in mixed culture is significantly different from pure culture
      and explain the difficulty to find robust quality indices for this product.

PMID- 16949173
TI  - Aspects of prokaryotic genome research. Proceedings of the 2nd European
      Conference on Prokaryotic Genomes (PROKAGEN). September 2005. Gottingen, Germany.

PMID- 16949174
TI  - Application of high throughput cell array technology to FISH: investigation of
      the role of deletion of p16 gene in leukemias.
AB  - Bio-cell chip is a chip that has hundreds of types of cells arrayed and
      immobilized on a small slide. To elucidate the role of deletion of the p16 gene
      in hematologic malignancies, the bio-cell chip technique was applied to
      fluorescent in situ hybridization (FISH) study. We made a bio-cell chip with bone
      marrow specimen from 109 patients with acute lymphoblastic leukemia (ALL), 102
      patients with acute myelogenous leukemia (AML), 47 patients with chronic
      myelogenous leukemia (CML), and 25 patients with multiple myeloma (MM). A glass
      slide with 96 separated areas was fabricated, onto which was added
      methanol/acetic acid fixed cell suspensions for high-throughput FISH for p16.
      With the successful application of bio-cell chip technique, we found that the
      deletion of p16 contributed to the oncogenesis in acute leukemia, but not in
      chronic leukemia. In conclusion, the bio-cell chip, a cell version of ultrahigh
      throughput technology, was successfully applied to the FISH study, which can be
      utilized efficiently in the molecular cytogenetic investigation of hematologic
      malignancies.

PMID- 16949175
TI  - Plant cell proliferation inside an inorganic host.
AB  - In recent years, much attention has been paid to plant cell culture as a tool for
      the production of secondary metabolites and the expression of recombinant
      proteins. Plant cell immobilization offers many advantages for biotechnological
      processes. However, the most extended matrices employed, such as calcium
      alginate, cannot fully protect entrapped cells. Sol-gel chemistry of silicates
      has emerged as an outstanding strategy to obtain biomaterials in which living
      cells are truly protected. This field of research is rapidly developing and a
      large number of bacteria and yeast-entrapping ceramics have already been designed
      for different applications. But even mild thermal and chemical conditions
      employed in sol-gel synthesis may result harmful to cells of higher organisms.
      Here we present a method for the immobilization of plant cells that allows cell
      growth at cavities created inside a silica matrix. Plant cell proliferation was
      monitored for a 6-month period, at the end of which plant calli of more than 1 mm
      in diameter were observed inside the inorganic host. The resulting hybrid device
      had good mechanical stability and proved to be an effective barrier against
      biological contamination, suggesting that it could be employed for long-term
      plant cell entrapment applications.

PMID- 16949176
TI  - A pricing policy towards the sourcing of cheaper drugs in Cyprus.
AB  - In contrast to other EU countries, Cyprus lacks comprehensive health care
      coverage for its population, thus a significant portion of the population lacks
      insurance for medicines. Due to the small size of the country and small
      indigenous pharmaceutical industry, pharmaceuticals are mainly imported. Prices
      in the private sector are determined based on the ex-factory price from the
      country of origin. Distribution margins are calculated as a percentage of the
      import price, which creates perverse incentives for wholesalers to import
      products from high price countries, or import very expensive products, to
      maximize their income. In this article, we compare pharmaceutical prices in
      Cyprus to other EU counties with higher or similar GDP per capita and found
      Cyprus to be a high price country. We then propose a new pricing system to change
      wholesaler incentives, which would encourage them to shop around for the best buy
      in Europe. Prices can be set based on average prices from a basket of European
      countries, and adjusted to reflect the GDP per capita level in Cyprus. This will
      establish the wholesale price that the government will accept, and wholesalers
      can procure products from any country at a lower rate. Thus, wholesalers would be
      encouraged to go for the lowest prices and the authorities would be indifferent
      to the actual price they obtain, so long as the necessary criteria (good
      manufacturing practice, safety, effectiveness and efficacy) are met. Our proposal
      has implications for low and middle income countries where this system of
      pharmaceutical pricing and wholesaler incentives can be used.

PMID- 16949177
TI  - Field-scale demonstration of induced biogeochemical reductive dechlorination at
      Dover Air Force Base, Dover, Delaware.
AB  - Biogeochemical reductive dechlorination (BiRD) is a new remediation approach for
      chlorinated aliphatic hydrocarbons (CAHs). The approach stimulates common sulfate
      reducing soil bacteria, facilitating the geochemical conversion of native iron
      minerals into iron sulfides. Iron sulfides have the ability to chemically reduce
      many common CAH compounds including PCE, TCE, DCE, similar to zero valent iron
      (Fe(0)). Results of a field test at Dover Air Force Base, Dover, Delaware, are
      given in this paper. BiRD was stimulated by direct injection of Epson salt
      (MgSO(4).7H(2)O) and sodium (L) lactate (NaC(3)H(5)O(3)) in five injection wells.
      Sediment was sampled before and 8 months after injection. Significant iron
      sulfide minerals developed in the sandy aquifer matrix. From ground water
      analyses, treatment began a few weeks after injection with up to 95% reduction in
      PCE, TCE, and cDCE in less than 1 year. More complete CAH treatment is likely at
      a larger scale than this demonstration.

PMID- 16949178
TI  - Melanoma cell-derived vascular endothelial growth factor induces endothelial
      tubulogenesis within fibrin gels by a metalloproteinase-mediated mechanism.
AB  - Angiogenesis is a process required not only for embryonal development but is
      encountered in wound healing and in pathological situations such as tumour
      growth. In vitro, formation of capillary-like structures can be induced by
      seeding human microvascular endothelial cells (HDMECs) on top of a fibrin matrix
      in the presence of phorbol 12-myristate 13-acetate (PMA) as a stimulating agent.
      In this study, we show that supernatants collected from high-invasive melanoma
      cells (BLM) induce the formation of tubular structures similar to PMA treatment
      whereas supernatants from low-invasive cells (WM164) did not. Analysis of
      proteins secreted into the supernatant of both melanoma cell lines identified
      differential expression of several pro-angiogenic proteins in high- and low
      invasive melanoma cells. Vascular endothelial growth factor (VEGF) was strongly
      expressed by high- but not by low-invasive melanoma cells. Neutralisation of VEGF
      as well as inhibition of matrix metalloproteases (MMPs) using the broad spectrum
      MMP inhibitor 1,10-phenanthroline, both strongly reduced the melanoma-induced
      tube formation. PMA treatment of HDMECs on a fibrin matrix stimulated MT1-MMP
      synthesis, indicating that this protease is involved in PMA-induced angiogenesis.
      In addition, stimulation of HDMECs by supernatants of BLM melanoma cells resulted
      in a strong induction of ADAM-15, which is known to act as a metalloproteinase.
      In conclusion, these results show that VEGF released by melanoma cells is an
      important mediator of neo-vascularisation and that this process depends on the
      presence of metalloproteinases.

PMID- 16949179
TI  - Presynaptic mechanisms underlying the alpha-lipoic acid facilitation of glutamate
      exocytosis in rat cerebral cortex nerve terminals.
AB  - The antioxidant alpha-lipoic acid has been reported to prevent and reverse age
      related impairments in learning and memory. However, it is unclear how alpha
      lipoic acid improves cognitive function. In this study, the effect of alpha
      lipoic acid on the release of endogenous glutamate from rat cerebrocortical nerve
      terminals (synaptosomes) was examined. We found that alpha-lipoic acid potently
      facilitated 4-aminopyridine (4AP)-evoked glutamate release, and this release
      facilitation results from an enhancement of vesicular exocytosis and not from an
      increase of non-vesicular release. Examination of the effect of alpha-lipoic acid
      on cytosolic [Ca(2+)] revealed that the facilitation of glutamate release was
      associated with an increase in voltage-dependent Ca(2+) influx. Consistent with
      this, alpha-lipoic acid-mediated facilitation of glutamate release was completely
      prevented in synaptosomes pretreated with a wide spectrum blocker of the N- and
      P/Q-type Ca(2+) channels, omega-conotoxin MVIIC. The facilitatory effect of alpha
      lipoic acid on Ca(2+) influx was not due to an increase of synaptosomal
      excitability because alpha-lipoic acid did not alter the 4AP-evoked
      depolarization of the synaptosomal plasma membrane potential. In addition, both
      ionomycin and hypertonic sucrose-induced glutamate release were enhanced by alpha
      lipoic acid. Furthermore, disruption of cytoskeleton organization with
      cytochalasin D occluded the facilitatory effect of alpha-lipoic acid on 4AP or
      ionomycin-evoked glutamate release. These results suggest that the antioxidant
      alpha-lipoic acid enhances the Ca(2+) entry through presynaptic N- and P/Q-type
      Ca(2+) channels as well as the vesicular release machinery to cause an increase
      in evoked glutamate release from rat cerebrocortical synaptosomes. Also,
      activation of PKA and PKC may underlie, at least in part, the alpha-lipoic acid
      mediated facilitation of glutamate release observed here as alpha-lipoic acid
      enhanced 4AP and ionomycin-evoked glutamate release were significantly attenuated
      by PKA and PKC inhibitors. This finding may provide some information regarding
      the mechanism of action of alpha-lipoic acid in the central nervous system (CNS).

PMID- 16949180
TI  - The effect of oral glutamine on 5-fluorouracil/leucovorin-induced
      mucositis/stomatitis assessed by intestinal permeability test.
AB  - BACKGROUND & AIMS: Systemic chemotherapy may damage gastrointestinal epithelium.
      Mucositis is associated with increased intestinal permeability (IP). It is known
      that IP test with chromium 51-ethylene diaminetetra-acetate (51Cr-EDTA) is a
      useful tool to assess the mucositis. Oral glutamine supplements (OGS) may have a
      role in the prevention of chemotherapy-induced mucositis/stomatitis. The aim of
      this study was to characterize the relationship between the urinary excretion of
      51Cr-EDTA and the severity of mucositis, and the effect of OGS on 5
      fluorouracil/leucovorin (FU/LV)-induced mucositis/stomatitis. METHODS: Fifty-one
      patients with advanced or metastatic cancer received FU/LV chemotherapy. The
      control group included 18 healthy volunteers. IP was assessed via the measurement
      of 51Cr-EDTA urinary excretion after oral challenge, on days 7 after the
      discontinuation of chemotherapy. Of the 51 patients, 22 patients received OGS (30
      g/day) and 29 received only best supportive care (BSC). Glutamine supplementation
      continued for 15 days. It was initiated at least 3 days before the beginning of
      chemotherapy. Mucositis/stomatitis was graded according to version 3.0 of the
      Common Terminology Criteria for Adverse Events. RESULTS: In the chemotherapy
      group, the median (25 percentile, 75 percentile) IP test score was significantly
      higher than those of the control group [6.78% (4.63, 10.66) vs. 2.17% (1.38,
      2.40), P<0.001]. The severity of stomatitis was significantly correlated with IP
      test scores (r=0.898, P<0.001). In the OGS group, the median IP test score was
      significantly lower than that of the BSC group [4.69% (3.10, 6.48) vs. 8.54%
      (6.48, 15.31), P<0.001]. A mucositis/stomatitis of grade 2-4 was observed in two
      patients of the OGS group (9%), and in 11 patients (38%) in the BSC group
      (P<0.001). CONCLUSIONS: The IP test may be a useful tool in the evaluation of
      mucositis/stomatitis. OGS may exert a protective effect on FU/LV-induced
      mucositis/stomatitis. Further studies, however, will be necessary to define the
      role of glutamine supplementation in FU/LV-induced mucositis/stomatitis.

PMID- 16949181
TI  - Antigenicity and immunogenicity of the N-terminal 33-kDa processing fragment of
      the Plasmodium falciparum merozoite surface protein 1, MSP1: implications for
      vaccine development.
AB  - The Plasmodium falciparum merozoite surface protein 1 (MSP1), MSP1-42 and MSP1-19
      are protective malaria vaccines. MSP1-42 is cleaved to form MSP1-33 and MSP1-19.
      The role of MSP1-33 in immunity is unclear. We investigated the antibody
      responses to MSP1-33; and to MSP1-33Trunc, in which major conserved sequences
      were excised. While anti-MSP1-33 antibodies were subdominant in the anti-MSP1-42
      responses, immunizations with MSP1-33 or MSP1-33Trunc induced high levels of
      antibodies reactive with MSP1-42 or whole merozoites. Anti-MSP1-33 and anti-MSP1
      33Tunc antibodies crossreacted with both allelic forms of MSP1-42. Anti-MSP1-33
      sera were ineffective in inhibiting parasite growth in vitro; but they
      significantly enhanced the activities of sub-optimal concentrations of the
      inhibitory anti-MSP1-42 sera. Thus, immunization strategies with MSP1-based
      vaccines may benefit from co-induction of anti-MSP1-33 responses to enhance
      efficacy and potency.

PMID- 16949182
TI  - Intranasal administration of chlamydial outer protein N (CopN) induces protection
      against pulmonary Chlamydia pneumoniae infection in a mouse model.
AB  - Chlamydia pneumoniae is an intracellular pathogen that grows inside a vacuole,
      referred to as an inclusion. C. pneumoniae possess a type III secretion system
      (TTSS), which allows them to secrete effector molecules into the inclusion
      membrane and to the host cell cytosol. Proteins such as chlamydial outer protein
      N (CopN) that associate with the inclusion membrane are potential targets for the
      host's MHC-dependent antigen presentation, thereby representing ideal antigen
      candidates for T cell-based vaccination. The results of this study showed that
      intranasal immunization of BALB/c mice with heat-aggregated CopN protein and an
      Escherichia coli heat-labile toxin (LT) induced a strong immune response,
      detected as antigen-specific antibody production, lymphocyte proliferation and
      IFN-gamma production. Furthermore, the immunization induced statistically
      significant protection against intranasal C. pneumoniae challenge, the level of
      which correlated with the magnitude of CopN-specific lymphocyte proliferation.
      Both heat-aggregation of the antigen and the presence of LT adjuvant were
      required for maximal protective effect.

PMID- 16949183
TI  - Re: seroepidemiology study of rubella antibodies among pregnant women from seven
      Asian countries: evaluation of the rubella vaccination program in Taiwan.

PMID- 16949184
TI  - The effect of vaccination on foot and mouth disease virus transmission among
      dairy cows.
AB  - The aim of this study was to quantify the effect of a single vaccination of dairy
      cows on foot and mouth disease virus (FMDV) transmission. To estimate if
      vaccination could significantly reduce virus transmission, we performed two
      replicates of a transmission experiment with one group of vaccinated and one
      group of non-vaccinated dairy cows (ten animals per group). Half of both groups
      were intranasally inoculated, with FMDV field isolate O/NET2001, and housed with
      the other half of the group (contact-exposed cows) from the next day onwards.
      Virus transmission was quantified by estimating the reproduction ratio R, which
      is the average number of secondary cases caused by one infectious animal. In the
      non-vaccinated groups all cows became infected and Rnv was significantly above 1.
      In the vaccinated groups infection was demonstrated in three inoculated cows, and
      no transmission was observed (Rv was 0, not significantly below 1). Transmission
      was significantly reduced in the groups of vaccinated cows when compared to the
      groups of unvaccinated cows. Our findings indicate that after a single
      vaccination cows are protected against infection of FMD and that most likely no
      virus transmission will occur within a vaccinated herd.

PMID- 16949185
TI  - The effect of lower extremity fatigue on shock attenuation during single-leg
      landing.
AB  - BACKGROUND: The forces that are imposed on the body due to landings must be
      attenuated primarily in the lower extremity. Muscles assist in the absorption of
      these forces, and it has been shown that a fatigued muscle decreases the body's
      ability to attenuate shock from running. The purpose of the study was to
      determine the effect of lower extremity fatigue on shock attenuation and joint
      mechanics during a single-leg drop landing. METHODS: Ten active male participants
      were recruited (eight used for analysis). Each participant took part in a fatigue
      landing protocol. This protocol included cycles of a drop landing, a maximal
      countermovement jump, and five squats, repeated until exhaustion. Accelerometers
      attached to the skin measured tibia and head accelerations. Lower extremity
      kinematics were collected using an electromagnetic tracking system and kinetics
      were collected using a forceplate. A repeated-measures ANOVA (P<0.05) was
      performed on each of the dependent variables across the cycles of the fatigue
      protocol. FINDINGS: Fatigue was induced, however there was no significant change
      in shock attenuation throughout the body. Hip and knee flexion increased and
      ankle plantarflexion decreased at touchdown with fatigue. Hip joint work
      increased and ankle work decreased. INTERPRETATION: This change in work
      distribution is thought to be a compensatory response to utilize the larger hip
      extensors that are better suited to absorb the mechanical energy of the impact.
      The results suggested that the lower extremity is able to adapt to fatigue though
      altering kinematics at impact and redistributing work to larger proximal muscles.

PMID- 16949186
TI  - Preliminary kinematic evaluation of a new stance-control knee-ankle-foot
      orthosis.
AB  - BACKGROUND: Stance-control knee-ankle-foot orthoses permit free knee motion in
      swing while providing knee flexion resistance in stance for individuals with
      quadriceps muscle weakness. However, some stance-control knee-ankle-foot orthoses
      require full knee extension to engage the knee-joint lock, thereby not providing
      knee support when climbing stairs or stepping over curbs. Stance-control knee
      ankle-foot orthoses that do support a flexed knee are either heavy, bulky,
      expensive, offer a limited number of locking positions, or cause noise. This
      paper presents a preliminary kinematic evaluation of a new stance-control knee
      ankle-foot orthosis that was designed to address these limitations. METHODS:
      Kinematic gait analysis was performed on three male knee-ankle-foot-orthosis
      users with knee extensor weakness in at least one limb (mean age: 56.3 years (SD
      4.0)). Three walking trials were performed with the subjects' current knee-ankle
      foot-orthosis and then the new stance-control knee-ankle-foot orthosis (non
      randomized before-after trial). Subjects completed a questionnaire about the new
      stance-control knee-ankle-foot orthosis and current knee-ankle-foot-orthosis.
      FINDINGS: A mean increase in knee flexion of 21.1 degrees (SD 8.2) during swing
      and a greater total knee range of motion was found when walking with the new
      stance-control knee-ankle-foot orthosis. Two knee-ankle-foot-orthosis users
      experienced a reduction in pelvic obliquity and hip abduction angle abnormalities
      when walking with the stance-control knee-ankle-foot orthosis. Two out of three
      subjects preferred walking with the new stance-control knee-ankle-foot orthosis
      over their prescribed knee-ankle-foot-orthosis. INTERPRETATION: The new stance
      control knee-ankle-foot orthosis permitted improved gait kinematics for knee
      ankle-foot-orthosis users while providing knee support in stance and free knee
      motion in swing at appropriate instants in the gait cycle. Overall, the new
      stance-control knee-ankle-foot orthosis provided more natural gait kinematics for
      orthosis users compared to conventional knee-ankle-foot-orthoses.

PMID- 16949187
TI  - Influence of gender, estrogen and exercise on anterior knee laxity.
AB  - BACKGROUND: Researchers have theorized that the disproportionate number of
      anterior cruciate ligament injuries in females, as compared to males, may be
      related to knee laxity, which in turn may be influenced by hormones. The purpose
      of this study was to investigate the collective effects of gender, estrogen and
      exercise on knee laxity. METHODS: Subjects consisted of 12 females and 12 males
      with no history of lower extremity injury. Serum estrogen levels and knee laxity
      were measured for the female subjects at specific times to represent three
      menstrual cycle phases while knee laxity of the male subjects was measured on
      three different days. For each data collection session, knee laxity was measured
      just prior to and immediately following an exercise protocol. Separate repeated
      measures ANOVAs were used to compare estrogen levels across the phases and
      analyze the laxity data. FINDINGS: Females exhibited greater knee laxity than
      males both pre- and post-exercise across all phases of the menstrual cycle.
      Estrogen fluctuations across the menstrual cycle did not modify knee laxity in
      females. Prior exercise induced equivalent increases in knee laxity in males and
      females across the data collection periods and irrespective of estrogen
      concentration. INTERPRETATION: If the anterior cruciate ligament is more
      distensible during athletic activities, it may be less capable of providing the
      necessary stability in order to prevent injury. This decreased stability may be
      contributing to the female athlete's increased incidence of anterior cruciate
      ligament injury. Overall, if females experience greater knee laxity during
      athletic activities, specific training strategies to compensate for these
      differences are warranted.

PMID- 16949188
TI  - Historical trends in persistent organic pollutants and metals recorded in
      sediment from Lake Ellasjoen, Bjornoya, Norwegian Arctic.
AB  - Ellasjoen receives contaminants from both atmospheric and biological transport
      (seabird guano). Historical trends of selected persistent organic pollutants and
      metals were determined by interpretation of down-core contaminant profiles in
      conjunction with sediment layer ages, determined by the (210)Pb method.
      Polychlorinated biphenyls (PCBs) and dichloro-diphenyl-trichloroethane and
      metabolites (DDTs) increased from about 1930 until 1970 (max. sum PCBs 71.8 ng/g
      dry weight (dw), max sum DDTs 4.0 ng/g dw), declining afterwards to 46.4 ng/g dw
      and 1.6 ng/g dw, respectively. Polybrominated diphenylethers (PBDEs)
      concentrations are increasing in Ellasjoen, reaching 0.73 ng/g dw in 2001.
      Hexabromocyclododekane (HBCD) was measured only in sediment from 1-2 cm depth
      (0.43 and 3.88 ng/g dw of alpha- and gamma-HBCD, respectively). Most metals (As,
      Cd, Co, Ni and Zn) showed a similar pattern as PCBs. No clear trends were
      observed for Cr, Pb or V. Mercury (Hg) has increased gradually since the
      beginning of the industrial era.

PMID- 16949189
TI  - Exaggerated leftward bias in the mental number line of patients with
      schizophrenia.
AB  - Several visuo-motor tasks can be used to demonstrate biases towards left
      hemispace in schizophrenic patients, suggesting a minor right hemineglect. Recent
      studies in neglect patients used a new number bisection task to highlight a
      lateralized defect in their visuo-spatial representation of numbers. To test a
      possible lateralized representational deficit in schizophrenia, we used the
      number bisection task in 11 schizophrenic patients compared to 11 healthy
      controls. Participants were required to orally indicate the central number of an
      interval orally presented. Whereas healthy subjects showed no significant bias,
      schizophrenic patients presented a significant leftward bias. Therefore, these
      results suggest an impairment in higher order representations of the number space
      in patients with schizophrenia, an impairment that is qualitatively similar to
      the deficit described in neglect patients.

PMID- 16949190
TI  - Development of antidotes: problems and strategies.
AB  - Antidotes against chemical warfare agents are "orphan drugs" given that these
      poisonings are rare. Therefore, they are of limited interest to the
      pharmaceutical industry. For this reason, and recognizing the increasing threat
      of terrorist or asymmetrical use of chemical warfare agents, the responsibility
      for research into medical countermeasures against these weapons is of primary
      interest to armies. Accordingly, the research activities of the Bundeswehr
      Institute of Pharmacology and Toxicology are dedicated to improving diagnosis,
      prophylaxis and therapy of individuals who are exposed to a chemical agent. Here,
      antidote development and testing are a high priority in the research program,
      particularly with respect to organophosphorus (OP) nerve agents and sulphur
      mustard. The Institute has been coordinating research activities undertaken in
      house and in collaboration with external researchers. The research program aims
      to develop primarily in vitro models to minimize the sacrifice of animals, using
      strategies, which involve human material early in antidote testing. An animal
      model using isolated mouse diaphragm demonstrated the correlation between AChE
      activity and neuromuscular function. A similar relationship was found between
      erythrocyte AChE and neuromuscular function in patients with acute OP pesticide
      poisoning. In vitro rate constants of the various reactions that are involved in
      enzyme inhibition and reactivation using human material were used for prediction
      of what would happen in vivo. This prediction could be confirmed in a patient
      with acute OP pesticide poisoning. Finally, computer models are being established
      to estimate the therapeutic effect of an antidote in various human poisoning
      scenarios. This approach is necessary to compensate for the lack of human
      clinical pharmacodynamic studies that are usually required for drug regulatory
      approval, given the obvious ethical issues preventing human volunteer studies
      with these agents.

PMID- 16949192
TI  - Salivary mutans streptococci counts as indicators in caries risk assessment in 6
      7-year-old Chinese children.
AB  - OBJECTIVES: This study aimed to determine whether salivary mutans streptococci
      (MS) counts in Chinese children had any value in the prediction of new caries in
      the permanent dentition in the age interval of 6.5-8.5 years. METHODS: Four
      hundred and thirty-three 6-7-year-old children participated in this 2-year
      longitudinal study. Salivary MS counts were obtained at baseline with the spatula
      method. Dentin and enamel caries was recorded at baseline and at the follow-up, 2
      years later. Spearman's correlation coefficients were computed. Past caries
      experience variables at baseline were entered into a multiple regression model
      with caries increment of the permanent dentition as dependent variable. MS counts
      were subsequently entered into the model to assess the additional caries
      predictive value. RESULTS: Spearman's correlation coefficient for MS counts and
      caries experience of the primary dentition at baseline was 0.48 and for MS counts
      and caries increment in the permanent dentition 0.12. In the multiple regression
      model caries increment of the permanent dentition had an adjusted R2 of 0.17 when
      the past caries experience variables were entered. Adding MS counts in the
      regression model did not change the R2 value. CONCLUSIONS: Salivary MS counts did
      not add any caries predictive value when past caries experience variables were
      used as caries predictors in this Chinese child population.

PMID- 16949191
TI  - Aluminum bioavailability from the approved food additive leavening agent acidic
      sodium aluminum phosphate, incorporated into a baked good, is lower than from
      water.
AB  - There are estimates of oral aluminum (Al) bioavailability from drinking water,
      but little information on Al bioavailability from foods. Foods contribute
      approximately 95% and drinking water 1-2% of the typical human's daily Al intake.
      The objectives were to estimate oral Al bioavailability from a representative
      food containing the food additive acidic sodium aluminum phosphate (acidic SALP),
      a leavening agent in baked goods. Rats were acclimated to a special diet that
      resulted in no stomach contents 14 h after its withdrawal. They were trained to
      rapidly consume a biscuit containing 1.5% acidic SALP. Oral Al bioavailability
      was then determined from a biscuit containing 1% or 2% acidic SALP, synthesized
      to contain (26)Al. The rats received concurrent (27)Al infusion. Blood was
      repeatedly withdrawn and serum analyzed for (26)Al by accelerator mass
      spectrometry. Total Al was determined by atomic absorption spectrometry. Oral
      (26)Al bioavailability was determined from the area under the (26)Al, compared to
      (27)Al, serum concentrationxtime curves. Oral Al bioavailability (F) from biscuit
      containing 1% or 2% acidic (26)Al-SALP averaged approximately 0.11% and 0.13%;
      significantly less than from water, which was previously shown to be
      approximately 0.3%. The time to maximum serum (26)Al concentration was 4.2 and 6h
      after consumption of biscuit containing 1% or 2% (26)Al-acidic SALP,
      respectively, compared to 1-2h following (26)Al in water. These results of oral
      Al bioavailability from acidic (26)Al-SALP in a biscuit (F approximately 0.1%)
      and results from (26)Al in water (F approximately 0.3%) x the contributions of
      food and drinking water to the typical human's daily Al intake ( approximately 5
      10mg from food and 0.1mg from water, respectively) suggest food provides
      approximately 25-fold more Al to systemic circulation, and potential Al body
      burden, than does drinking water.

PMID- 16949194
TI  - Quantitative analysis of intact fetal cells in maternal plasma by real-time PCR.
AB  - OBJECTIVE: Fetal genetic materials in maternal circulation might be potentially
      used for non-invasive prenatal diagnosis (NIPD). In this study, we quantitatively
      analysed the intact fetal cells existing in maternal plasma, which would be a
      special method of NIPD. STUDY DESIGN: Eleven samples from preeclamptic patients,
      two samples from patients with RhD incompatibilities, and 30 samples from normal
      pregnancies as controls were collected. The intact cells in the plasma fraction
      were separated by centrifugation at high speed. The intact cell pellets were
      washed with PBS to remove any cell-free DNA. RESULTS: We were able to detect
      intact fetal cells in 3 out of 11 preeclamptic plasma samples from women carrying
      male fetuses, and from both plasma samples of RhD incompatibility affected
      pregnancies. However, intact fetal cells were not detected in all the 16 normal
      pregnancies with a male fetus, although cell-free fetal DNA was detected in all
      these cases. CONCLUSIONS: Intact fetal cells might be present in maternal plasma.
      However, the rarity of these cells limits their use for reliable, non-invasive
      prenatal diagnosis. The detection of such cells was successful in some
      preeclamptic and RhD incompatibility samples, not in the normal controls.
      Therefore, as opposed to free fetal DNA in maternal blood the use of intact fetal
      cells does not provide a reliable mode for NIPD.

PMID- 16949193
TI  - Paraoxonase gene polymorphism, serum lipid, and oxidized low-density lipoprotein
      in preeclampsia.
AB  - OBJECTIVES: Human paraoxonase-1 (PON-1) is thought to play a role in preeclampsia
      and atherosclerosis, mainly through a reduction in low-density lipoprotein
      oxidation. Oxidized low-density lipoprotein (LDL) is very important in
      endothelial dysfunction of preeclampsia. The aim of the present study was to
      investigate the association between PON1 gene polymorphism and preeclampsia and
      to determine concentrations of serum lipid in preeclampsia patients. We aimed
      also to evaluate serum oxidized LDL levels in normal and preeclampsia patients.
      STUDY DESIGN: We performed the present study in 57 control women and 32
      preeclampsia patients. PON-1 genotypes were determined by polymerase chain
      reaction amplification and restriction fragment length polymorphism. Serum
      triglyceride, cholesterol, high-density lipoprotein cholesterol, and low-density
      lipoprotein cholesterol levels were measured. We also measured serum levels of
      oxidized LDL by ELISA method. RESULTS: There was no significant difference in
      PON1 genotype frequencies between the control and preeclampsia patients. The
      levels of serum cholesterol and high-density lipoprotein were significantly lower
      in preeclampsia patients compared with that of the control women (p=0.05, and
      p<0.01, respectively). The serum levels of oxidized LDL in preeclampsia patients
      were significantly higher than those in the control women (p=0.001). CONCLUSIONS:
      These findings support the importance of the atherogenic lipid profile and
      oxidized LDL that is enhanced in preeclampsia, and these findings may be
      significant contributors to endothelial dysfunction.

PMID- 16949195
TI  - Air assimilative capacity-based environment friendly siting of new industries--a
      case study of Kochi region, India.
AB  - Air pollution has become a matter of grave concern, particularly in mega-cities
      and urban areas, where the situation is alarming and becoming more and more
      severe day-by-day and warrants, therefore, careful planning to facilitate future
      industrial development. Site selection, with the objective of minimizing adverse
      environmental impacts based on environmental criteria is a vital prerequisite,
      particularly for air polluting industries. In order to locate any air polluting
      industry, the assimilative capacity of the region needs to be assessed carefully
      and planned accordingly, so that the receiving environment is not adversely
      affected. Assimilative capacity of a region/airshed, widely represented through
      the ventilation coefficient by many researchers in the past, does not give a
      clear picture about the amount of emission load that can be assimilated in a
      given region. The ventilation coefficient, at best, can only present a broad
      picture about the air pollution dispersion potential (low, medium or high) of the
      region. A modified approach, which utilizes air quality modelling as a tool to
      estimate the maximum allowable emission load that a region can assimilate without
      violating the stipulated standards, has been used for estimating the assimilative
      capacity of the air environment. Details of this approach have been presented in
      this paper through a case study carried out for the Kochi region, located in the
      Kerala State of India. A variety of emission and meteorological scenarios have
      been considered and critical emission loads have been estimated. This approach
      shall provide necessary technical guidance to the environmental regulatory
      authorities as well as to the industries in planning environment friendly
      industrial development.

PMID- 16949196
TI  - Application of adaptive heuristic criticism control (AHCC) to dye wastewater.
AB  - This paper presents an experimental application of AHCC to study the coagulation
      process of wastewater treatment in a dye plant. Also this study includes a series
      of tests in which an AHCC control was used for pH control. The performance
      results of the AHCC controller are compared with the results obtained by using a
      conventional proportional-integral-derivative (PID) algorithm. It is useful to
      compare PID with AHCC to illustrate the extreme range of the nonlinearity of the
      dye wastewater treatment process. Although the removal of pollutants from
      wastewater is similar with AHCC and PID, our results show excellent AHCC
      performance in the region where conventional PID control fails.

PMID- 16949197
TI  - Nephron-sparing surgery for renal tumours: acceleration and facilitation of the
      laparoscopic technique.
AB  - OBJECTIVE: Present our surgical technique for and experience with laparoscopic
      partial nephrectomy (LPN) for renal tumours during warm ischaemia. METHODS:
      Twenty-five patients underwent LPN during warm ischaemia via a transperitoneal
      four-trocar approach. Mean tumour size was 26.2+/-7.3mm (range: 11-39 mm).
      Sixteen tumours were exophytic, 7 endophytic, and 2 central. The renal vessels
      were secured by an umbilical tape and occluded by a self-made Rumel tourniquet.
      Tumours were excised with a cold Endo-shear. The interstitial tissue and
      collecting system was closed using a running suture secured by two resorbable
      clips. Parenchymal edges were approximated using a running suture over a
      haemostatic bolster. The threads were secured by non-resorbable clips. During
      follow-up, renal function was evaluated by determination of serum creatinine,
      (99m)Tc-mercaptoacetyltriglycine scintigraphy, and parenchymal transit time.
      RESULTS: Mean ischaemia time was 28.9+/-5.2 min (range: 19-40 min) and the mean
      blood loss was 177.4+/-285.5 ml (range: 50-1500 ml). No intraoperative
      complications occurred and no patient needed conversion to open surgery. Surgical
      margins were negative in all patients. One postoperative surgical-related
      perirenal haematoma occurred, which was treated conservatively (no transfusions
      required). None of the patients had a urinary leak. During a mean follow-up of
      6.2 mo (range: 1-15 mo), none of the patients had local or port-site recurrence
      or distant metastasis. Parenchymal transit time was increased in 1 of 10
      investigated patients (ischaemia time: 26 min), indicating ischaemic parenchymal
      damage. CONCLUSION: Our technical refinements for LPN during warm ischaemia have
      widened indications to more complex tumours. The use of clips rather than knot
      tying made the procedure easier and faster and allowed completion of the suturing
      during an acceptable warm ischaemia time. The self-made Rumel tourniquet is safe
      and efficient for vessel control and occlusion. These improvements increase
      feasibility so that LPN can be used by more laparoscopic urologic surgeons.

PMID- 16949198
TI  - Do we need the final results of the ERSPC trial?

PMID- 16949199
TI  - Radical cystectomy--often too late? Yes, but ...

PMID- 16949200
TI  - Phosphodiesterase type 5 inhibitors: the day after.
AB  - OBJECTIVE: Review the literature on phosphodiesterase type 5 inhibitors (PDE5
      Is), addressing critical issues in their current and future use, assessing
      unanswered questions, and identifying research needs. METHODS: A MEDLINE search
      was conducted on PDE5-Is, with emphasis on clinical trials and experience, for
      interpretation and analysis of their present and future role. RESULTS: Although
      approximately 40 million patients with erectile dysfunction have been treated
      successfully worldwide with the three available PDE5-Is, inappropriate
      instructions, lack of follow-up, and lack of patient-centered care models are the
      main reasons for "non-response," leading to drop-out rates of >50%. Patients with
      severe neurologic damage, diabetes mellitus, or severe vascular disease may be
      resistant to PDE5-Is. Preservation of corporal smooth muscle with chronic
      administration of PDE5-Is has been reported and substantial evidence indicates
      that these drugs have beneficial effects on endothelium and cardiovascular
      function; sildenafil has been approved for the treatment of idiopathic pulmonary
      hypertension. Improvement of lower urinary tract symptoms in men with benign
      prostatic hyperplasia after PDE5-I administration has been also suggested.
      CONCLUSIONS: The data indicate the necessity for (1) exploration of the
      pharmacologic characteristics of the three PDE5-Is; (2) research on their
      pharmacologic differences because some actions seems to be drug-specific; (3)
      development of alternative management strategies, such as chronic, low, everyday
      doses of PDE5-Is, if the monthly cost is affordable; and (4) clinical trials on
      use of PDE5-Is to treat other chronic conditions. The door for innovative
      therapeutic approaches will open, specifically for cross-risk factor treatment
      with PDE5-Is or their use in combination treatments or new multimodal pills that
      take advantage of drugs that exert pleiotropic vascular actions.

PMID- 16949201
TI  - Microbial activity in weathering columns.
AB  - The aim of the present work was to evaluate the metabolic activity of the
      microbial population associated with a pyritic tailing after a column-weathering
      test. For this purpose, a column 150cm high and 15cm diameter was used. The solid
      was a tailing with 63.4% pyrite and with minor amounts of Cu, Pb and Zn sulfides
      (1.4, 0.5 and 0.8%, respectively). The column model was the habitual one for
      weathering tests: distilled water was added at the top of the column; the water
      flowed down through tailings and finally was collected at the bottom for chemical
      and microbiological analysis. Weathering was maintained for 36 weeks. The results
      showed a significant presence of microbial life that was distributed selectively
      over the column: sulfur- and iron-oxidizing aerobic bacteria were in the more
      oxygenated zone; anaerobic sulfur-reducing bacteria were isolated from the
      samples taken from the anoxic part of the column. Activity testing showed that
      (oxidizing and reducing) bacteria populations were active at the end of the
      weathering test. The quality of the water draining from the column was thus the
      final product of biological oxidation and reduction promoted by the bacteria
      consortia.

PMID- 16949203
TI  - Severity of AD/HD symptoms and efficiency of attentional resource allocation.
AB  - This study investigated the mechanism that underlies the inefficient allocation
      of attentional resources in Attention-Deficit/Hyperactivity Disorder (AD/HD). The
      P300 event-related brain potential (ERP) was elicited from 24 healthy adults
      using a visual three-stimulus oddball paradigm (standard, 70%; target, 15%; non
      target, 15%) and the degree of their AD/HD symptoms was assessed by using AD/HD
      symptom scales. Target stimulus was a circle and standard stimulus was an "X".
      Two task conditions were defined according to the non-target stimulus type
      (typical or novel): a triangle for the typical condition and colored non
      repetitive novel stimuli for the novel condition. In both conditions, target and
      non-target elicited P300s. A ratio of non-target P300 to target P300 amplitude
      was used to assess the efficiency of attentional resource allocation; low ratio
      indicates the efficient allocation of attentional resource. The correlation
      analysis revealed a strong positive correlation between the AD/HD symptom score
      and the P300 amplitude ratio in the typical condition (r=.80), while only a weak
      positive correlation was observed in the novel condition (r=.23). The present
      study found that the commonality of task-relevant and task-irrelevant
      information, rather than the stimulus novelty of task-irrelevant information,
      induces the inefficient allocation of attentional resources in AD/HD.

PMID- 16949202
TI  - Leaching behaviour of low level organic pollutants contained in cement-based
      materials: experimental methodology and modelling approach.
AB  - The aim of this paper is the investigation of the leaching behaviour of different
      porous materials containing organic pollutants (PAH: naphthalene and
      phenanthrene). The assessment methodology of long term leaching behaviour of
      inorganic materials was extended to cement solidified organic pollutants. Based
      on a scenario-approach considering environmental factors, matrix and pollutants
      specificities, the applied methodology is composed of adapted equilibrium and
      dynamic leaching tests. The contributions of different physical and chemical
      mechanisms were identified and the leaching behaviour was modelled. The physical
      parameters of the analysed reference and polluted materials are similar. A
      difference in the pore size distribution appears for higher naphthalene content.
      The solubility of the PAH contained in the material is affected by the ionic
      strength and by the presence of a co-solvent; the solution pH does not influence
      PAH solubility. The solubility of the major mineral species is not influenced by
      the presence of the two PAH nor by the presence of the methanol as co-solvent in
      the range of the tested material compositions. In the case of the leaching of a
      monolith material the main transport mechanism is the diffusion in the porous
      system. For both mineral and organic species we observed at least two dynamic
      domains. At the beginning of the leaching process the released flux is due to the
      surface dissolution and to the diffusion of the main quantity dissolved in the
      initial pore solution. The second period is governed by a stationary regime
      between dissolution in pore water and diffusion. The model, coupling transport
      and chemical phenomena in the pore solution, at the monolith surface and in the
      leachate simulates satisfactory the release for both mineral and organic species.

PMID- 16949204
TI  - GM1 up-regulates Ubiquilin 1 expression in human neuroblastoma cells and rat
      cortical neurons.
AB  - GM1 ganglioside was reported to mediate the amyloid beta-protein (Abeta)
      secretion and accumulation in the pathogenesis of Alzheimer's disease (AD). The
      objective of this project was to comprehend the underlying molecular changes
      related to amyloid beta-protein precursor (APP) processing pathway induced by
      GM1. Using suppression subtractive hybridisation (SSH), we detected one prominent
      sequence with increased expression in human neuroblastoma cells that stably
      transfected with human APP695 cDNA treated with GM1. This transcript has high
      identity to human Ubiquilin 1 gene. Differential expression was initially
      confirmed by dot blot hybridization. This result was further authenticated with
      quantitative real-time polymerase chain reaction (RT-PCR) analysis. Furthermore,
      using Western blots, we discovered that GM1 stimulated the expression of
      Ubiquilin 1 in human neuroblastoma cells and rat cortical neurons while other
      gangliosides Asialo-GM1 and GD1b did not. Ubiquilin 1 is one of the candidate
      genes of AD, which have been shown to modulate the gamma-secretase components in
      the proteolytic processing of APP, and is therefore a putative candidate for
      further investigation of GM1 mechanisms in the etiology and pathology of AD.

PMID- 16949205
TI  - List effect in apraxia assessment.
AB  - Imitation tests encompassing intermingled meaningful and meaningless items are
      normally used to assess ideomotor apraxia, implicitly assuming that they would
      test the lexical and the non-lexical route, respectively. However, these mixed
      lists might induce a "list composition" effect similar to that found in word
      recognition studies where familiar material can be processed via the non-lexical
      route. This hypothesis was put to test by examining praxis skills of 23 left
      hemisphere damaged patients using the same gestures in two formats: pure and
      mixed lists (i.e., meaningless or meaningful gestures administered separately or
      intermingled, respectively). Results showed that patients performed better on the
      imitation task when pure lists were used. Moreover, asymmetries of performance
      were observed. Patient SL scored better in the imitation of meaningful gestures
      in the pure list than in the mixed list condition. Patient CA performed poorly in
      the imitation of meaningless gestures only in the mixed list condition.
      Dissociations observed in imitation tasks could be biased by the use of mixed
      lists. Also "pure" lists should be used for the diagnosis of imitation deficits
      in apraxia.

PMID- 16949206
TI  - Fluoro-Jade: new fluorescent marker of Rosenthal fibers.
AB  - Rosenthal fibers are homogeneous eosinophilic masses found in astrocytes that are
      composed of glial fibrillary acidic protein (GFAP) aggregates along with
      chaperone proteins and other unknown components. Rosenthal fiber formation is a
      pathological hallmark of Alexander disease and its detection is diagnostically
      significant. However, the lack of a specific fluorescent marker has greatly
      limited the histochemical characterization of Rosenthal fibers. Here, we report
      for the first time a fluorescent marker of Rosenthal fibers called Fluoro Jade.
      Fluoro Jade-positive masses were seen in samples of Alexander disease brain,
      pilocytic astrocytoma, and in brain tissue from a mouse model of Alexander
      disease. Fluoro Jade co-labeled tissue samples stained with GFAP
      immunofluorescence. Our results indicated that Fluoro Jade labeled Rosenthal
      fibers, and that Rosenthal fibers could be labeled with antibodies of interest in
      combination with Fluoro Jade staining.

PMID- 16949207
TI  - Localization of L-type calcium channel Ca(V)1.3 in cat lumbar spinal cord--with
      emphasis on motoneurons.
AB  - Voltage-dependent persistent inward currents (PICs) which underlie the plateau
      potentials are an important intrinsic property of spinal motoneurons.
      Electrophysiological experiments have indicated that a subtype of the low
      threshold L-type calcium channel, Ca(V)1.3, mediates this current. In mouse and
      turtle lumbar spinal cord it has been shown that these channel proteins are
      mainly found on motoneuron dendrites. In the present study we have used
      immunohistochemistry to locate these channels in lumbar spinal neurons,
      especially motoneurons, of the cat. The results indicate that Ca(V)1.3
      immunoreactivity was unevenly distributed among the laminae of the spinal grey
      matter. The small neurons in superficial dorsal horn (laminae I-III) were
      sparsely and weakly labelled, while large neurons in ventral horn were frequently
      and densely labelled. Groups of motoneurons in lamina IX that were immunoreactive
      to choline acetyltransferase also co-expressed Ca(V)1.3. The immunoreactivity was
      mainly associated with neuronal somata and proximal dendrites. Double staining
      with antibodies against Ca(V)1.3 and MAP2 (a dendritic marker) showed that some
      fine fibres, which may include distal dendrites, were also labelled. These
      results in the cat spinal cord show some differences from studies in mouse and
      turtle motoneurons where the immunoreactivity against this channel was mainly
      localized to the dendrites.

PMID- 16949208
TI  - Curcumin activated both receptor-mediated and mitochondria-mediated proteolytic
      pathways for apoptosis in human glioblastoma T98G cells.
AB  - The therapeutic effect of curcumin (CCM), a polyphenolic compound from the
      rhizome of Curcuma longa, has not yet been examined in glioblastoma. We used
      human glioblastoma T98G cells to explore the efficacy of CCM for inducing
      apoptosis and identifying proteolytic mechanisms involved in this process. Trypan
      blue dye exclusion test showed decrease in cell viability with increasing dose of
      CCM. Wright staining and ApopTag assay showed, respectively, morphological and
      biochemical features of apoptosis in T98G cells exposed to 25 microM and 50
      microM of CCM for 24 h. Treatment with CCM activated receptor-mediated pathway of
      apoptosis as Western blotting showed activation of caspase-8 and cleavage of Bid
      to tBid. Besides, CCM caused an increase in Bax:Bcl-2 ratio, and mitochondrial
      release of cytochrome c, Second mitochondrial activator of caspases/Direct IAP
      binding protein with low pI (Smac/Diablo), and apoptosis-inducing-factor (AIF)
      indicating involvement of mitochondria-mediated pathway as well. Down regulation
      of the nuclear factor kappa B (NFkappaB), increased expression of inhibitor of
      nuclear factor kappa B alpha (IkappaB alpha), and decreased expression of
      inhibitor-of-apoptosis proteins (IAPs) such as c-IAP1 and c-IAP2 in T98G cells
      following CCM treatment suggested suppression of survival signal. Activation of
      caspase-9 and caspase-3 was detected in generation of 35 kD and 20 kD active
      fragments, respectively. Calpain and caspase-3 activities cleaved 270 kD alpha
      spectrin at specific sites to generate 145 kD spectrin break down product (SBDP)
      and 120 kD SBDP, respectively. Our results strongly suggest that CCM induced both
      receptor-mediated and mitochondria-mediated proteolytic mechanisms for induction
      of apoptosis in T98G cells.

PMID- 16949209
TI  - Differential effect of glutamate transporter inhibition on EPSCs in the morphine
      naive and morphine tolerant neonatal spinal cord slice.
AB  - Opioid analgesic tolerance is a phenomenon defined as a need for increasingly
      higher doses of opiates to maintain suitable pain relief following repeated drug
      exposure. Research suggests that analgesic tolerance may result from heightened
      NMDA receptor (NMDAR) activity, but little is known regarding the mechanisms by
      which this elevated NMDAR activity develops. Recent evidence suggests that
      glutamate transporter down-regulation follows repeated opiate exposure and
      contributes to heightened pain sensitivity. Though glutamate transporter
      inhibition has been shown to increase activity of spinal cord neurons, it is
      unknown whether this increase contributes to the heightened NMDAR activity that
      underlies opiate tolerance. We directly tested this hypothesis by comparing the
      effects of glutamate transporter inhibition on excitatory post-synaptic currents
      (EPSCs) in the spinal cord dorsal horn of opiate naive and opiate tolerant rats.
      We show that non-selective glutamate transporter inhibition increases the rate of
      spontaneous excitatory post-synaptic currents (sEPSCs) in the opiate naive, but
      not opiate tolerant slice. This potentiation occurs in the presence of the sodium
      channel blocker tetrodotoxin (TTX) and is blocked by the NMDAR antagonist D-2
      amino-5-phosphonovalerate (APV). The sEPSC rate is elevated at baseline in the
      opiate tolerant spinal cord slice compared to the opiate naive slice, and
      glutamate transporter inhibition eliminates this difference. Taken together, we
      conclude that glutamate transporter inhibition directly contributes to heightened
      NMDAR activity. Furthermore, we propose that the increased neural activity
      observed in the opiate tolerant slice is due to a state of glutamate transporter
      down-regulation and resultant heightened NMDAR activity.

PMID- 16949210
TI  - Deep burn of the hands: Early surgical treatment avoids the need for late
      revisions?
AB  - An eight years experience in the management of deep hand burns is presented. We
      reviewed 116 cases of patients surgically treated with escarectomy and skin
      autograft. Seventy eight of them underwent early surgery within the first 4-6
      days from injury, while 38 were conservatively treated in the fist stage and only
      lately surgery was performed (usually after the 14th day). In all patients, we
      applied the same post operative topic treatment and rehabilitation protocol.
      Several months after first admission, only 6(7.7%) of early treated patients
      needed secondary correction for unaesthetic and functionally debilitating scars
      versus 14(36.8%) of the late treated group. Our review confirm the importance of
      performing early surgery of deep burns of the hands, whenever possible, in order
      to achieve best results and shows it's utility in reducing re-admissions for
      secondary revisions.

PMID- 16949211
TI  - Nutrition in burns: need for an aggressive dynamic approach.
AB  - INTRODUCTION: Extensive burns elicit a pronounced metabolic response causing
      physiological derangements leading to the hyper-metabolic state. The hyper
      metabolic response is accompanied by severe catabolism and a loss of lean body
      mass and also by a progressive decline of host defenses that impairs the
      immunological response. AIMS: A study was conducted in our hospital to assess
      various aspects of nutritional management of burns considering the ground
      realities of general hospital. The main aim of the study was to assess the use of
      early naso-gastric tube insertion, charting out daily calorie intake and to
      appropriately decrease the deficit with use of low cost feeds taking in to
      consideration the local dietary habits. MATERIALS AND METHODS: A total 138 cases
      were studied prospectively during April 2003 to March 2005, which were compared
      with 206 controls taken retrospectively from April 2000 to March 2003. The cases
      and controls were compared regarding the mortality rate, average days of stay and
      number of procedure done after dividing them in to various categories (%Burns)
      using the Z-test and student t-test. DISCUSSION AND CONCLUSION: The use of early
      naso-gastric tube insertion, charting out daily calorie intake and using low cost
      feeds consistent with local dietary habits lead to a significant decrease in
      average number of days and the number of procedures in 20-39% TBSA burns; and
      caused the significant decrease in mortality, average number of days and the
      number of procedure in 40-59%TBSA burns.

PMID- 16949212
TI  - The creatine transporter mediates the uptake of creatine by brain tissue, but not
      the uptake of two creatine-derived compounds.
AB  - Hereditary creatine transporter deficiency causes brain damage, despite the brain
      having the enzymes to synthesize creatine. Such damage occurring despite an
      endogenous synthesis is not easily explained. This condition is incurable,
      because creatine may not be delivered to the brain without its transporter.
      Creatine-derived compounds that crossed the blood-brain barrier in a transporter
      independent fashion would be useful in the therapy of hereditary creatine
      transporter deficiency, and possibly also in neuroprotection against brain anoxia
      or ischemia. We tested the double hypothesis that: (1) the creatine carrier is
      needed to make creatine cross the plasma membrane of brain cells and (2) creatine
      derived molecules may cross this plasma membrane independently of the creatine
      carrier. In in vitro mouse hippocampal slices, incubation with creatine increased
      creatine and phosphocreatine content of the tissue. Inhibition of the creatine
      transporter with 3-guanidinopropionic acid (GPA) dose-dependently prevented this
      increase. Incubation with creatine benzyl ester (CrOBzl) or phosphocreatine-Mg
      complex acetate (PCr-Mg-CPLX) increased tissue creatine content, not
      phosphocreatine. This increase was not prevented by GPA. Thus, the creatine
      transporter is required for creatine uptake through the plasma membrane. Since
      there is a strong indication that creatine in the brain is mainly synthesized by
      glial cells and transferred to neurons, this might explain why hereditary
      transporter deficiency is attended by severe brain damage despite the possibility
      of an endogenous synthesis. CrOBzl and PCr-Mg-CPLX cross the plasma membrane in a
      transporter-independent way, and might be useful in the therapy of hereditary
      creatine transporter deficiency. They may also prove useful in the therapy of
      brain anoxia or ischemia.

PMID- 16949213
TI  - Lipopolysaccharide induces preproenkephalin transcription in hypophysiotropic
      neurons of the rat paraventricular hypothalamic nucleus suggesting a
      neuroendocrine role for enkephalins during immune stress.
AB  - Opioids have impact on stress responses and possess immune modulatory functions.
      We have previously shown that immune stress elevates the levels of
      preproenkephalin transcript in a variety of autonomic structures in the rat
      brain, including the paraventricular hypothalamic nucleus. By using in situ
      hybridization with an intronic probe recognizing the preproenkephalin
      heteronuclear RNA combined with retrograde tract tracing, we examined the
      efferent target of the enkephalinergic neurons in the paraventricular
      hypothalamic nucleus that display induced transcriptional activity during immune
      challenge. Rats were first given i.p. injections of the tracer substance Fluoro
      Gold, which following this route of administration is taken up only by nerve
      terminals residing outside the blood-brain barrier, and were then given an i.v.
      injection of lipopolysaccharide. Neuronal cell bodies retrogradely labeled with
      Fluoro-Gold were detected by immunohistochemistry, and-using a dual-labeling
      approach-the same cells were then examined for their expression of
      preproenkephalin heteronuclear RNA. We found that over 90% of the neurons that
      expressed preproenkephalin heteronuclear RNA also contained Fluoro-Gold. In
      addition, approximately 40% of the neurons expressing preproenkephalin
      heteronuclear RNA co-expressed mRNA for corticotropin-releasing hormone, the main
      adrenocorticotropic hormone secretagogue. These data show that the
      paraventricular hypothalamic neurons that display induced preproenkephalin
      transcription following immune challenge are almost exclusively hypophysiotropic
      neurons, indicating a role for enkephalin in the hypothalamic control of hormone
      release during infectious and inflammatory conditions.

PMID- 16949214
TI  - Renewal of an extinguished instrumental response: neural correlates and the role
      of D1 dopamine receptors.
AB  - Contexts play an important role in controlling the expression of extinguished
      behaviors. We used an ABA renewal design to study the neural correlates, and role
      of D1 dopamine receptors, in contextual control over extinguished instrumental
      responding. Rats were trained to respond for a sucrose reward in one context (A).
      Responding was then extinguished in the same (A) or different (B) context. Rats
      were tested for responding in the original training context (A). Return to the
      original training context after extinction (group ABA) was associated with a
      return of responding. Three distinct patterns of Fos induction were detected on
      test: 1) ABA renewal was associated with selective increases in c-Fos protein
      induction in basolateral amygdala, ventral accumbens shell, and lateral
      hypothalamus (but not in orexin- or melanin-concentrating hormone (MCH)
      hypothalamic neurons); 2) being placed in the same context as extinction training
      (AAA or ABB) was associated with a selective decrease in c-Fos induction in
      rostral agranular insular cortex; 3) being placed in any context on test was
      associated with the up-regulation of c-Fos induction in anterior cingulate,
      dorsomedial accumbens shell, accumbens core, lateral septum, and substantia
      nigra. The return of responding in ABA renewal was prevented by pre-treatment
      with the D1 dopamine receptor antagonist SCH23390 (10 microg/kg; s.c.). SCH23390
      also suppressed basal and renewal-associated c-Fos protein induction throughout
      accumbens, and, selectively suppressed renewal-associated c-Fos induction in
      lateral hypothalamus. These results suggest that renewal of extinguished
      responding for a sucrose reward depends on a distributed neural circuit involving
      basolateral amygdala, ventral accumbens shell, and lateral hypothalamus. D1
      dopamine receptors within this circuit are essential for renewal. The results
      also suggest that rostral agranular insular cortex may play an important role in
      suppressing reward-seeking after extinction training.

PMID- 16949215
TI  - The cannabinoid receptor agonist, WIN 55,212-2, inhibits cool-specific lamina I
      medullary dorsal horn neurons.
AB  - Cannabinoid receptor agonists have been demonstrated to inhibit medullary and
      spinal cord dorsal horn nociceptive neurons. The effect of cannabinoids on
      thermoreceptive specific neurons in the spinal or medullary dorsal horn remains
      unknown. In the present study, single-unit recordings from the rat medullary
      dorsal horn were performed to examine the effect of a cannabinoid receptor
      agonists on cold-specific lamina I spinothalamic tract neurons. The cannabinoid
      CB1/CB2 receptor agonist, WIN 55,212-2 (WIN-2), was locally applied to the
      medullary dorsal horn and the neuronal activity evoked by cooling the receptive
      field was recorded. WIN-2 (1 microg/microl and 2 microg/microl) significantly
      attenuated cold-evoked activity. Co-administration of the CB1 receptor antagonist
      SR 141716 with WIN-2 did not affect cold-evoked activity. These results
      demonstrate a potential mechanism by which cannabinoids produce hypothermia, and
      also suggest that cannabinoids may affect non-noxious thermal discrimination.

PMID- 16949216
TI  - Lectures are such an effective teaching method because they exploit evolved human
      psychology to improve learning.
AB  - Lectures are probably the best teaching method for many students in many
      circumstances; especially for communicating conceptual knowledge, and where there
      is a significant knowledge gap between lecturer and audience. However, the lack
      of a convincing rationale has been a factor in under-estimating the importance of
      lectures, and there are many who advocate their replacement with written
      communications or electronic media. I suggest that lectures are so effective
      because they exploit the spontaneous human aptitude for learning from spoken
      (rather than written) information. Literacy is a recent cultural artefact, and
      for most of their evolutionary history humans communicated by direct speech. By
      contrast with speech, all communication technologies--whether reading a book or a
      computer monitor--are artificial and unnatural. Furthermore, learning is easier
      during formal, quiet, real-time social events. The structure of a lecture
      artificially manipulates human psychology to increase vigilance, focus attention,
      and generate authority for the lecturer--all of which make communications more
      memorable for the student. Instead of trying to phase-out lectures, we should
      strive to make them better by understanding that lectures are essentially formal,
      spoken, social events.

PMID- 16949217
TI  - Nuclear localization of poly(A)+ mRNA following siRNA reduction of expression of
      the mammalian RNA helicases UAP56 and URH49.
AB  - UAP56 is a eukaryotic RNA helicase that is important for mRNA splicing and
      nuclear export. Although most eukaryotes have a single protein corresponding to
      UAP56, we have shown previously that in human and mouse cells there is a second
      protein, URH49, which is 90% identical to UAP56. Both proteins interact with the
      mRNA export factor Aly and both are able to rescue the loss of Sub2p (the yeast
      homolog of UAP56), suggesting that both proteins have similar functions. However,
      the two helicases have different expression profiles in different tissues and in
      growth-stimulated cells, which raises the possibility that they might be involved
      in the splicing and export of non-identical populations of mRNA. In the present
      study, we have used RNA interference to further explore the functions of these
      two helicases. Reducing the expression of either URH49 or UAP56 in HeLa cells had
      little effect on cell proliferation or expression of a co-transfected gene.
      However, analysis of poly(A)+ RNA localization by fluorescent in situ
      hybridization revealed a speckled pattern of RNA accumulation throughout the
      nucleus. Reducing the expression of both helicases resulted in a major reduction
      in reporter gene expression as well as cell death within 72 h. We also observed a
      more prominent speckled pattern of nuclear poly(A)+ RNA accumulation as well as
      reduced accumulation in the cytoplasmic compartment. These observations suggest
      that both helicases have essential but largely overlapping functions in the
      processing and export of mammalian mRNAs.

PMID- 16949218
TI  - The phosphatidylinositol 3-kinase/Akt pathway regulates the HCCR-1 oncogene
      expression.
AB  - The human cervical cancer oncogene HCCR-1 is overexpressed in various human
      cancers, and might function as a negative regulator of the p53 tumor suppressor.
      To determine the regulatory pathway involved in the HCCR-1 gene expression, we
      searched the 5' flanking region of HCCR-1 and identified HCCR-1 promoter
      including putative homeodomain protein binding sites. The level of HCCR-1
      expression was increased during the mouse embryogenesis. Expression of
      phosphatidylinositol 3-kinase (PI3K) in NIH/3T3 cells activated the HCCR-1
      promoter. This promoter was also activated by wild type Akt but not by dominant
      negative Akt in K562 cells. In addition, the level of HCCR-1 was decreased by
      PI3K inhibitor, LY-294002, in a dose dependent manner. Northern blot analysis
      revealed that the HCCR-1 gene expression was down-regulated by LY-294002. These
      results suggest that the HCCR-1 oncogene expression was regulated by the PI3K/Akt
      signaling pathway.

PMID- 16949219
TI  - Induction of cytochromes P450, caspase-3 and DNA damage by PCB3 and its
      hydroxylated metabolites in porcine ovary.
AB  - Polychlorinated biphenyl (PCBs) levels of tens and hundreds of pg/ml for
      individual congeners are measured in human follicular fluid. PCB3 (4
      chlorobiphenyl), caused a significant increase in estradiol secretion in porcine
      granulose-theca cell co-cultures and its two metabolites, 4-OH-PCB3 and 3,4-diOH
      PCB3, were even more potent than PCB3 itself [Ptak, A., Ludewig, G., Lehmler,
      H.J., Wojtowicz, A.K., Robertson, L.W., Gregoraszczuk, E.L. 2005. Comparison of
      the actions of 4-chlorobiphenyl and its hydroxylated metabolites on estradiol
      secretion by ovarian follicles in primary cells in culture. Reprod. Toxicol. 20,
      57-64]. The question is whether these follicle cells are potentially able to
      metabolize PCB3 to hydroxylated and genotoxic or cytotoxic intermediates. We
      report here that granulose-theca co-cultures express xenobiotic-metabolizing
      cytochrome P450 activities, with CYP1A1>CYP2B>>CYP1A2. A significant increase in
      CYP1A1 and 2B, but not CYP1A2, activity was seen in cells that were exposed to 6
      ng/ml PCB3 or 20 nM 17-beta-estradiol. An increase in caspase-3 activity,
      indicative for apoptosis, was only observed in PCB3-exposed cells after 24 h
      exposure. Genotoxicity, determined with the Comet assay, was initially reduced
      after 24 h exposure to PCB3 and both metabolites compared to untreated controls,
      followed by a significant transient increase in Comets at the 4 and 24 h time
      point with PCB3 and 4-OH-PCB3. 3,4-diOH-PCB3 induced a significant increase only
      after 72 h of recovery. We hypothesize that these biphasic damage kinetics may be
      due to cross-links caused by adduct formation. These results show for the first
      time that granulose-theca cells in co-culture express CYP1A1, 2B and 1A2
      activities and that PCBs at concentrations that are reached in the environment
      induce genotoxicity in granulosa cells.

PMID- 16949220
TI  - The impact of controlled nutrition during the dry period on dairy cow health,
      fertility and performance.
AB  - Average dairy herd fertility is declining, with more serves per successful
      conception, extended calving intervals and increased culling due to failure to
      rebreed, all adding significant costs to milk production. Genetics, management
      and nutrition have all contributed to this decline in fertility; the paper
      focuses primarily on nutritional issues. The extent of body condition loss after
      calving and its possible impact on fertility is considered, with evidence that
      this phenomenon is common in many herds irrespective of average milk yields. Body
      tissue mobilisation after calving increases the flux of non-esterified fatty
      acids to the liver and pathways of fatty acid metabolism are considered.
      Particular attention is given to the effects of high plasma non-esterified fatty
      acid levels on fat accumulation in liver cells and possible impacts on nitrogen
      and glucose metabolism. Current nutritional practices with early lactation cows
      which aim to stimulate milk yield and peak milk production but have been shown to
      exacerbate body condition loss, are reviewed. The paper also considers cow health
      issues during the peri-parturient period and how these may affect milk yield and
      fertility. It is concluded that current feeding practices for dry cows, with the
      provision of increasing amounts of the lactation ration during the Close-up
      period to accustom the rumen microbes and offset the expected reduction in feed
      intake as pregnancy reaches term, have largely failed to overcome peri-parturient
      health problems, excessive body condition loss after calving or declining
      fertility. From an examination of the energy and protein requirements of dry
      cows, it is suggested that current Close-up feeding practices can lead to luxury
      intakes of nutrients that can increase fat deposition in the viscera and the
      liver. Under such conditions, metabolism of nutrients by the cow may be
      compromised. In contrast, limited feeding throughout the whole dry period has
      been shown to prevent many of the problems which can affect peri-parturient cows.
      A new feeding strategy based on a low energy: high fibre ration (9 MJ
      metabolisable energy and 130 g crude protein/kg ration dry matter) containing
      high levels of chopped straw and offered ad libitum as a total mixed ration
      throughout the whole dry period is proposed. The performance of 32 dairy farms in
      France where this strategy has been adopted for at least 3 years is provided,
      with positive outcomes now being obtained by UK and Irish dairy farmers.
      Independent US research evidence has confirmed some of these benefits whilst
      limited data on cow fertility is presented. It is hypothesised that luxury
      feeding during the dry period can cause cows to become insulin resistant leading
      to an increased risk of type II diabetes. Such cows are likely to have poorer
      fertility whilst possible mechanisms which increase the risk of peri-parturient
      health problems are discussed. Further research to understand the mechanisms of
      these effects is required and is currently ongoing. However the magnitude of the
      effects noted on an increasing number of dairy farms suggests this approach to
      feeding the dry cow is capable of bringing real benefits to many dairy herds in
      terms of fewer health problems, reduced body condition loss and improved
      fertility.

PMID- 16949221
TI  - Effect of milling conditions on the solid-state conversion of ranitidine
      hydrochloride form 1.
AB  - Powder samples of ranitidine hydrochloride forms 1 and 2 were milled using a
      vibrational ball mill (Retsch MM301) for periods up to 240min at 4, 12 and 35
      degrees C. X-ray powder diffraction (XRPD), diffuse reflectance infrared Fourier
      transform spectroscopy (DRIFTS), solid-state nuclear magnetic resonance (NMR) and
      differential scanning calorimetry (DSC) were used to monitor solid-state
      properties of the milled samples. Milling of form 1 at 4 degrees C led to a
      powder temperature of 36 degrees C in the milling chamber and produced only
      amorphous drug; at 12 degrees C (powder temperature 45 degrees C) and at 35
      degrees C (powder temperature 62 degrees C) progressive transformation of form 1
      via amorphous drug to form 2 occurred. DSC of the milled samples showed a glass
      transition at 13-30 degrees C and a crystallization exotherm (T(c)) between 30
      and 65 degrees C if the sample contained amorphous drug. The behaviour of the
      solid was speculated to be influenced by the relationship between powder
      temperature and T(c); at powder temperatures below T(c), amorphous drug is formed
      but no crystallization of form 2 occurs; at temperatures close to T(c), amorphous
      content initially increases with transformation to form 2 on continued milling.
      At temperatures much higher than T(c), at intermediate stages, less amorphous
      drug but both form 1 and form 2 are recovered, but continued milling gives only
      form 2. Form 2 did not transform to form 1 under any conditions used in this
      study.

PMID- 16949222
TI  - Melt granulation using a twin-screw extruder: a case study.
AB  - The purpose of this study was to use a twin-screw extruder for melt granulation.
      Polyethylene glycols (PEG 400 and 4000) were used as binders for the development
      of a drinking water formulation with immediate drug release. The effect of drug
      content, PEG 400/4000-ratio, surfactant (type and concentration) and granulation
      temperature on granule properties and dissolution characteristics was determined.
      The granulation temperature had an important influence on the granule formation.
      High yield (95% of the granules <1400 microm) was obtained only at a temperature
      near the melting point of PEG 4000. During granulation the drug of BCS class II
      was finely dispersed in the PEGs, creating a micro-environment around the drug
      particles enhancing the dissolution rate. To obtain complete drug release within
      10 min for a formulation containing 10% drug, the addition of 2% (w/w) surfactant
      (polysorbate 80 or Cremophor RH40) was required. At a higher drug content (20%),
      the PEG 4000 concentration had to be increased to 20% to improve granule
      properties and 4% polysorbate 80 was required to obtain 100% drug release. X-ray
      diffractograms showed distinct peaks of crystalline drug, the crystallinity of
      the drug did not change after 50 days, independent of the storage conditions.

PMID- 16949223
TI  - Solid state characterization of olanzapine polymorphs using vibrational
      spectroscopy.
AB  - FT-Raman, infrared and near infrared investigations of two polymorphs of
      olanzapine are presented, establishing the main features that allow the
      discrimination of these crystalline forms using vibrational spectroscopic
      methods. Ab initio calculations on the basis of the density functional theory
      were used to determine the stable conformations. The calculated vibrational
      spectra were compared to the experimental ones in order to identify the
      conformers corresponding to each polymorph and to assign the vibrational bands to
      the internal vibrations of the olanzapine molecule. Our results support the
      hydrogen bonding pattern proposed by the reported crystalline structure and
      provide valuable information on the structural and thermodynamical relationship
      between the investigated polymorphs.

PMID- 16949224
TI  - Stability of cosmetic formulations containing esters of vitamins E and A:
      chemical and physical aspects.
AB  - Cosmetic stability prediction relies on quantitative chemical determinations of
      active components after certain times and in different temperatures. However,
      physical stability, an important parameter in skin care products is not
      considered in these conditions. This study proposes the determination of cosmetic
      stability chemical and physical parameters validated by (HPLC) chromatography and
      rheological measurements, respectively, using a gel-cream containing retinyl
      palmitate and tocopheryl acetate as a model system. The predicted shelf life
      addresses both the physical and chemical aspects of the system. Results emphasize
      the importance of studying both parameters by showing the relation of components
      degradation and physical stability. Moreover, they contribute to an improved
      understanding of physical and chemical stability aspects of cosmetic
      formulations, mainly if they contain Vitamins A and E derivatives.

PMID- 16949225
TI  - Design of a transdermal delivery system for aspirin as an antithrombotic drug.
AB  - Aspirin has become the gold standard to which newer antiplatelet drugs are
      compared for reducing risks of cardiovascular diseases, while keeping low cost.
      Oral aspirin has a repertoire of gastrointestinal side effects even at low doses
      and requires high frequent dosing because it undergoes extensive presystemic
      metabolism. Transdermal delivery offers an alternative route that bypasses the
      gut and may be more convenient and safer for aspirin delivery especially during
      long-term use. This study comprised formulation of aspirin in different topical
      bases. Release studies revealed that hydrocarbon gel allowed highest drug
      release. In vitro permeation studies revealed high drug permeation from
      hydrocarbon gel. Several chemical penetration enhancers were monitored for
      augmenting the permeation from this base. Combination of propylene glycol and
      alcohol showed maximum enhancing effect and, hence, was selected for biological
      investigation. The biological performance of the selected formulation was
      assessed by measuring the inhibition of platelet aggregation relevant to
      different dosage regimens aiming to minimize both drug dose and frequency of
      application. The results demonstrated the feasibility of successfully influencing
      platelet function and revealed that the drug therapeutic efficacy in transdermal
      delivery system is dose independent. Biological performance was re-assessed after
      storage and the results revealed stability and persistent therapeutic efficacy.

PMID- 16949227
TI  - Taurine acts as a glycine receptor agonist in slices of rat inferior colliculus.
AB  - Taurine is an important endogenous amino acid for neural development and for many
      physiological functions, but little is known about its functional role in the
      central auditory system. We investigated in young rats (P10-P14) the effects of
      taurine on the neuronal responses and synaptic transmissions in the central
      nucleus of the inferior colliculus (ICC) with a brain slice preparation and with
      whole-cell patch-clamp recordings. Perfusion of taurine at 1mM reliably evoked a
      current across the membrane and decreased the input resistance in neurons of the
      ICC. Taurine also depressed the spontaneous and current-evoked firing of ICC
      neurons. All these effects were reversible after washout and could be blocked by
      3 microM strychnine, an antagonist of glycine receptors, but not by 10 microM
      bicuculline, an antagonist of GABA(A) receptors. When the inhibitory receptors
      were not pharmacologically blocked, taurine reversibly reduced the postsynaptic
      currents/potentials evoked by electrically stimulating the commissure of the
      inferior colliculus or the ipsilateral lateral lemniscus. The results demonstrate
      that taurine reduces the neuronal excitability and depresses the synaptic
      transmission in the ICC by activating glycine-gated chloride channels. Our
      findings suggest that taurine acts as a ligand of glycine receptors in the ICC
      and can be involved in the information processing of the central auditory system
      similarly like the neurotransmitter glycine.

PMID- 16949226
TI  - Identification of 17 hearing impaired mouse strains in the TMGC ENU-mutagenesis
      screen.
AB  - The Tennessee Mouse Genome Consortium (TMGC) employed an N-ethyl-N-nitrosourea
      (ENU)-mutagenesis scheme to identify mouse recessive mutants with hearing
      phenotypes. We employed auditory brainstem responses (ABR) to click and 8, 16,
      and 32 kHz stimuli and screened 285 pedigrees (1819 mice of 8-11 weeks old in
      various mixed genetic backgrounds) each bred to carry a homozygous ENU-induced
      mutation. To define mutant pedigrees, we measured > or = 12 mice per pedigree in
      > or = 2 generations and used a criterion where the mean ABR threshold per
      pedigree was two standard deviations above the mean of all offspring from the
      same parental strain. We thus identified 17 mutant pedigrees (6%), all exhibiting
      hearing loss at high frequencies (> or = 16 kHz) with an average threshold
      elevation of 30-35 dB SPL. Interestingly, four mutants showed sex-biased hearing
      loss and six mutants displayed wide range frequency hearing loss. Temporal bone
      histology revealed that six of the first nine mutants displayed cochlear
      morphological defects: degeneration of spiral ganglia, spiral ligament fibrocytes
      or inner hair cells (but not outer hair cells) mostly in basal turns. In contrast
      to other ENU-mutagenesis auditory screens, our screen identified high-frequency,
      mild and sex-biased hearing defects. Further characterization of these 17 mouse
      models will advance our understanding of presbycusis and noise-induced hearing
      loss in humans.

PMID- 16949228
TI  - Medicinal plants from the "Sierra de Comechingones", Argentina.
AB  - Argentina is a country with both rich floral biodiversity and cultural diversity.
      Traditional herbal medicines are important in the health care of most people, and
      rely heavily on the use of indigenous plants. An ethnobotanical survey of the
      "Sierra de Comechingones" made over a 26-year period (1979-2005), indicated that
      65 families and 149 different genuses were used in traditional medicines. The use
      of these medicines was observed to be widespread and prevalent over orthodox
      medicine. Medicinal native plants from this mountain range make up 31% of the
      total Argentina medicinal native flora. In addition, there are 15 endemic species
      that grow only in the region. The botanical name, popular uses, parts utilized,
      as well as the distribution of these medicinal plants from the "Sierra de
      Comechingones", Argentina, were summarized. Previous reports on phytochemical and
      biological activities in relation to cancer, antimicrobials and pesticides were
      also included.

PMID- 16949229
TI  - In vivo antidiabetic and antioxidant potential of Helichrysum plicatum ssp.
      plicatum capitulums in streptozotocin-induced-diabetic rats.
AB  - Helichrysum species (Asteraceae) are widely found in Anatolia. Decoction prepared
      from the capitulums of Helichrysum plicatum ssp. plicatum is used to alleviate
      the symptoms of diabetes mellitus in folk medicine. In the present study, the
      hypoglycaemic and antioxidant potential of Helichrysum plicatum ssp. plicatum was
      evaluated by using in vivo methods in normal and streptozotocin-induced-diabetic
      rats. After the oral administration of water and ethanolic extracts at doses of
      500mg/kg body weight prepared from the capitulums of plant, blood glucose levels
      were monitored at specific intervals. Tolbutamide was used as a reference drug at
      a dose of 100mg/kg. The experimental data indicated that water and ethanol
      extracts of capitulums demonstrate significant antihyperglycaemic and antioxidant
      activity in streptozotocin-induced rats which confirmed the folkloric
      utilization. In order to assess the role of polyphenolic components in the
      relevant activity, phenolic and flavonoid contents of each extract were also
      determined in terms of total phenols: 113.5+/-8.6mg (gallic acid equivalent/1g
      extract) and total flavanoids 50.5+/-1.9mg (quercetin equivalent/1g extract) for
      ethanol extract, total phenols: 75.9+/-3.7, flavonoids: 31.5+/-2.3 for water
      extract using Folin-Ciocalteu reagent.

PMID- 16949230
TI  - Evidence of anti-inflammatory effects of Passiflora edulis in an inflammation
      model.
AB  - The popular medicine Passiflora edulis has been used as a sedative, tranquilizer,
      against cutaneous inflammatory diseases and intermittent fever. Most of the
      pharmacological investigations of Passiflora edulis have been addressed to its
      Central Nervous System activities, such as anxiolytic, anticonvulsant and
      sedative actions. Otherwise, there are few reports about the anti-inflammatory
      activity of the Passiflora species. The aim of this study was to investigate the
      mechanism of the anti-inflammatory effect of aqueous lyophilized extract obtained
      from leaves of Passiflora edulis var. flavicarpa Degener (Passifloraceae) in the
      mouse model of pleurisy induced by carrageenan (Cg), bradykinin, histamine or
      substance P, observing the effects upon leucocytes migration, myeloperoxidase
      (MPO), nitric oxide (NO) concentrations and tumor necrosis factor-alpha
      (TNFalpha) and interleukin-1 beta (IL-1beta) levels. RESULTS: Passiflora edulis
      (250mg/kg) administered by intraperitoneal route (i.p.) inhibited the leukocyte,
      neutrophils, myeloperoxidase, nitric oxide, TNFalpha and IL-1beta levels (P<0.01)
      in the pleurisy induced by carrageenan. Passiflora edulis (250-500mg/kg, i.p.)
      also inhibited total and differential leukocytes in the pleurisy induced by
      bradykinin, histamine or substance P (P<0.05). CONCLUSION: Several mechanisms,
      including the inhibition of pro-inflammatory cytokines (TNFalpha, IL-1beta),
      enzyme (myeloperoxidase) and mediators (bradykinin, histamine, substance P,
      nitric oxide) release and/or action, appear to account for Passiflora edulis's
      actions.

PMID- 16949231
TI  - Effects of canthin-6-one alkaloids from Zanthoxylum chiloperone on Trypanosoma
      cruzi-infected mice.
AB  - Canthin-6-one (1), isolated from Zanthoxylum chiloperone (Rutaceae), possesses a
      broad sprectum of antifungal and leishmanicidal activities. In this study, we
      have examined the antiparasitic effects of canthin-6-one (1), 5-methoxycanthin-6
      one (2), canthin-6-one N-oxide (3), as well as that of the total alkaloids of
      Zanthoxylum chiloperone stem bark, in Balb/c mice infected either acutely or
      chronically with Trypanosoma cruzi. The compounds were administered orally or
      subcutaneously at 5mg/kg/day for 2 weeks, whereas the alkaloidal extract was
      given at 50mg/kg/day for 2 weeks. The antiparasitic activity was compared with
      that of benznidazole given at 50mg/kg/day for 2 weeks. In the case of acute
      infection, parasiteamia was significantly reduced following oral treatment with
      canthin-6-one (1). Moreover, the total alkaloids of Zanthoxylum chiloperone stem
      bark led to high levels of parasitological clearance. Seventy days post
      infection, the serological response in the acute model was significantly
      different between oral canthin-6-one (1) and benznidazole-treated mice. Chronic
      model of the disease showed that both canthin-6-one (1) and the alkaloidal
      extract at the above dosage induced 80-100% animal survival compared to untreated
      controls. These results indicate that canthin-6-one (1) exhibits trypanocidal
      activity in vivo in the mouse model of acute or chronic infection. This is the
      first demonstration of anti-Trypanosoma cruzi activity for a member of this
      chemical group (canthinones). Considering the very low toxicity of canthin-6-one
      (1), our results suggest that long-term oral treatment with this natural product
      could prove advantageous compared to the current chemotherapy of Chagas disease.

PMID- 16949232
TI  - Acute effect of Trema micrantha (Ulmaceae) on serum glucose levels in normal and
      diabetic rats.
AB  - Trema micrantha (Ulmaceae) ethanolic crude extract (ECE) was screened for its
      hypoglycemic activity (250, 500 and 1,000 mg/kg v.o.). The animals were divided
      in three groups for the evaluation of the hypoglycemic effect: normal rats, rats
      with alloxan-induced diabetes and hyperglycemic normal rats. The
      antihyperglycemic activity was compared to the treatment with glibenclamide, an
      oral hypoglycemic agent. Serum glucose was analyzed after the treatment of the
      animals. The acute treatment with Trema micrantha ECE (250 and 1,000 mg/kg)
      caused a significant decrease in the blood glucose levels in diabetic rats, but
      no effect was observed among the normal treated rats nor the hyperglycemic normal
      rats. Trema micrantha's leaves are a good candidate for alternative and/or
      complementary medicine in the management of diabetes mellitus, since they showed
      beneficial effects on blood glucose levels.

PMID- 16949233
TI  - Effect of aqueous extract of Ajuga iva supplementation on plasma lipid profile
      and tissue antioxidant status in rats fed a high-cholesterol diet.
AB  - The present study was designed to explore the possible antioxidant and
      hypolipidemic effects of the aqueous extract of Ajuga iva (0.5% in the diet) in
      rats fed a high-cholesterol (1%) diet (HCD). The results indicated that the HCD
      Ai versus HCD treatment led to many changes in biochemical parameters. They
      showed a decrease of plasma total cholesterol (TC) and VLDL-cholesterol but an
      increase of HDL(2)-cholesterol. The triacylglycerol contents were reduced in
      plasma and in VLDL. The lipid peroxidation determined by TBARS was decreased by
      75% in plasma. TBARS in liver, heart and kidneys were highly reduced excepted in
      the adipose tissue. Ajuga iva treatment enhanced superoxide dismutase activity in
      liver and kidney. Glutathione reductase activity was lowered in adipose tissue
      but increased in liver and in kidney. A significant increase was noted in
      glutathione peroxidase activity in liver, heart and kidney but a low value in
      adipose tissue was observed. In conclusion, the present study demonstrates that
      in addition to its potent TG and TC-lowering effects, Ajuga iva is effective in
      improving the antioxidant status by reducing lipid peroxidation in plasma and
      tissues and enhancing the antioxidant enzymes in rats fed high-cholesterol diet.
      Furthermore, Ajuga iva may reduce intestinal cholesterol absorption.

PMID- 16949234
TI  - Identification of necrophagous fly species using ISSR and SCAR markers.
AB  - Necrophagous fly is the most common insect evidence collected during a death
      investigation. We analyzed the DNA polymorphism among the five forensically
      important fly species, namely, Lucilia sericata, Aldrichina grahami, Chrysomya
      megacephala, Parasarcophaga crassipalpis and Musca domestica using inter simple
      sequence repeat (ISSR) method. Nine ISSR primers selected from 18 primers could
      amplify 105 clear and stable bands, of which 95 bands were polymorphic. Some
      primers produced completely different band pattern in different species,
      indicating that they can be used to identify these species. Aiming at obtaining
      more reliable markers that might be universally used, we started an effort to
      convert species-specific ISSR fragments into the sequence-characterized amplified
      region (SCAR) markers that can be used for the molecular diagnosis of the five
      species.

PMID- 16949235
TI  - Identification of human semenogelin in membrane strip test as an alternative
      method for the detection of semen.
AB  - Semenogelin (Sg), a protein originating in the seminal vesicles and a substrate
      for prostate specific antigen (PSA or p30), is a useful marker for the
      identification of semen. And detection of Sg has been available commercially in a
      membrane test recently. PSA is commonly used to detect semen in forensic
      significant samples taken from sexual assault cases. The strip PSA test has been
      available commercially from various manufacturers for many years. In this study,
      we evaluated two immunochromatographic membrane tests, one for Sg and the other
      for PSA by analyzing human semen, other human bodily fluids/materials including
      urine, blood, saliva, sweat, breast milk, vaginal secretion and fecal materials,
      semen from various animals and forensic casework samples. The data demonstrate
      that both Sg and PSA strip tests provide rapid and sensitive method for
      identification of seminal plasma. These results show that the
      immunochromatographic method for Sg detection is useful for the identification of
      seminal plasma in forensic samples, an alternative to the method for PSA
      detection.

PMID- 16949236
TI  - Synchronous squamous cell carcinoma and malignant lymphoma in the head and neck
      region.
AB  - Synchronous malignancy of squamous cell carcinoma (SCC) and malignant lymphoma
      (ML) in the head and neck region is extremely rare. Here, we report the case of a
      57-year-old man with a right-sided neck mass; he was referred to our hospital in
      September 2001. A series of staging work-ups revealed that he was simultaneously
      affected by oropharyngeal SCC and nasopharyngeal ML. He underwent conventional
      radiotherapy, and both the primary tumors showed complete remission. The
      metastatic lymph nodes showed poor response to the radiotherapy, and the patient
      was surgically salvaged by modified radical neck dissection. Although systemic
      chemotherapy against ML was scheduled, he refused the treatment and died of
      disseminated ML. It is essential to determine the lesion that should be given
      priority treatment in case of double primary malignancies; this can be
      facilitated by determining the prognosis of each malignancy.

PMID- 16949237
TI  - Hypopharyngeal squamous cell carcinoma bordering ectopic gastric mucosa "inlet
      patch" of the cervical esophagus.
AB  - OBJECTIVE: Ectopic gastric mucosa of the cervical esophagus, referred to as inlet
      patch (IP), is considered to be a common development abnormality of the
      esophagus. We report here a case of hypopharyngeal squamous cell carcinoma
      bordering on IP of the cervical esophagus. METHODS: A 44-year-old female
      underwent partial pharyngectomy, total laryngectomy, cervical esophagectomy, and
      bilateral neck dissection under the diagnosis of hypopharyngeal carcinoma.
      RESULTS: Resected specimens of the hypopharynx revealed a well-differentiated
      squamous cell carcinoma in the ulcerative tumorous lesion (3.5 cm x 0.5 cm). A
      brown patch (2 cm x 1.5 cm) bordering the anal aspect of the tumor comprised
      ectopic gastric mucosa of fundic type epithelium. Immunohistochemistry revealed
      the surface mucosal cells of this lesion were strongly positive for human gastric
      mucin (HGM) and the fundic cells were positive for gastrin. CONCLUSION: The
      hypopharyngeal squamous cell carcinoma likely developed in association with
      chronic irritation due to gastric acid from the IP. To our knowledge, this is the
      first reported case of squamous cell carcinoma related to IP.

PMID- 16949238
TI  - Three Japanese patients with glucose transporter type 1 deficiency syndrome.
AB  - We report three Japanese patients with glucose transporter type 1 deficiency
      syndrome (Glut1DS). Two patients had a normal erythrocyte 3-O-methylglucose
      (3OMG) uptake, one with a previously reported T295M substitution and the other
      with a novel 12-bp insertion at nt 1034-1035, ins CAGCAGCTGTCT. The third
      patient, with deficient 3OMG uptake, had a previously reported hot-spot mutation,
      R333W. All three patients responded to a ketogenic diet. All patients showed a
      significant improvement in ataxia, with blood beta-hydroxybutyrate (BOHB) levels
      ranging from 0.1 to 3mM. BOHB levels of at least 3mM were necessary to control
      seizures, and higher ketone levels are recommended to meet brain energy needs
      during development. FDG-PET scan, performed before and after a ketogenic diet in
      the R333W patient, did not change despite a clinical improvement. This clinical
      condition is treatable and early diagnosis is important.

PMID- 16949239
TI  - Caudal regression syndrome associated with the white matter lesions and
      chromosome 18p11.2 deletion.
AB  - Caudal regression syndrome (CRS) is a rare combination of congenital
      abnormalities characterized by caudal vertebral agenesis/dysgenesis that is
      usually associated with congenital anomalies of spinal cord, gastrointestinal and
      genitourinary organs. Although the exact teratogenic mechanism is not known, same
      environmental, e.g., hyperglycemia and genetic factors appears to play a crucial
      role in this fetopathy. Herein, we report an unusual case of CRS associated with
      unspecific white matter lesions and 18p-syndrome manifested by congenital ptosis,
      hypothyroidism, facial dysmorphy and chromosome 18p11.2 deletion.

PMID- 16949240
TI  - Progressive multifocal leukoencephalopathy in purine nucleoside phosphorylase
      deficiency.
AB  - Progressive multifocal leukoencephalopathy is a demyelinating disease caused by
      JC virus, an opportunistic infection of the central nervous system. Although the
      majority of cases are infected with the human immunodeficiency virus (HIV), other
      immunocompromised patients are also at risk. Purine nucleoside phosphorylase is
      an enzyme in the purine salvage pathway that reversibly converts inosine to
      hypoxanthine and guanosine to guanine. Purine nucleoside phosphorylase deficiency
      is a combined immunodeficiency with a profound cellular defect. Neurologic
      abnormalities are salient features of this syndrome. We describe for the first
      time a patient with this rare disorder presented with progressive multifocal
      leukoencephalopathy.

PMID- 16949241
TI  - Is there a role for CT in the neonate?
AB  - Choice of imaging modalities should be based on scientific proof and best
      practice guidelines. However, in the neonatal age group there is a paucity of
      medical evidence, and imaging is often guided by local experience, availability
      of equipment and expertise, and by logistical factors. This paper discusses
      possible indications for CT in the neonate, the associated radiation protection
      issues, common CT findings and potential pitfalls in technique and image
      interpretation. Due to the particular range of abnormalities in this age group,
      imaging must be tailored to the individual, and should in most cases be done in
      specialist units.

PMID- 16949242
TI  - Rapid quantification of malondialdehyde in plasma by high performance liquid
      chromatography-visible detection.
AB  - BACKGROUND: Malondialdehyde (MDA) is one of the better-known secondary products
      of lipid peroxidation, and it is widely used as an indicator of cellular injury.
      The employment of the thiobarbituric acid reactive substances (TBARS) technique
      to measure MDA has received criticism over the years because of its lack of
      specificity. Thus, a specific and reliable method for MDA determination in plasma
      by high performance liquid chromatographic (HPLC)-VIS was validated; alkaline
      hydrolysis, n-butanol extraction steps and MDA stability were established.
      METHODS: The plasma underwent alkaline hydrolysis, acid deproteinization,
      derivatization with TBA and n-butanol extraction. After this, MDA was determined
      at 532 nm by HPLC-VIS. The method was applied to 65-year-old subjects from a
      retirement home. RESULTS: The assay was linear from 0.28 to 6.6 microM. The
      reproducibility of intra-run was obtained with CV%<4% and the inter run with
      CV%<11%. The accuracy (bias) ranged from 2 to -4.1%, and the recovery was greater
      than 95%. The limit of detection (LOD) and limit of quantification (LOQ) were
      0.05 and 0.17 microM, respectively. For the stability test, every sample was
      stored at -20 degrees C. The plasma MDA was not stable when stored after the
      alkaline hydrolysis step, remained stable for 30 days after TBA derivatization
      storage and was stable for 3 days when stored after n-butanol extraction. The
      elderly subjects had MDA plasma levels of 4.45+/-0.81 microM for women and 4.60+/
      0.95 microM for men. CONCLUSION: The method is reproducible, accurate, stable,
      sensitive, and can be used in the routines in clinical laboratories. Besides,
      this technique presents advantages such as the complete release of protein bound
      MDA with the alkaline hydrolysis step, the removal of interferents with n-butanol
      extraction, mobile phase without phosphate buffer and rapid analytical processes
      and run times.

PMID- 16949243
TI  - Contemporary activity of meropenem and comparator broad-spectrum agents: MYSTIC
      program report from the United States component (2005).
AB  - The Meropenem Yearly Susceptibility Test Information Collection Program is a 9
      year-old antimicrobial resistance surveillance network of more than 100 medical
      centers worldwide, including 15 sites in the United States (US) that monitors the
      susceptibility of Gram-negative and Gram-positive bacterial pathogens especially
      to carbapenems. In 2005, the antimicrobial activity of 11 broad-spectrum agents
      was assessed against 2910 bacterial isolates (2493 Gram-negative and 417
      staphylococci) submitted from the US medical centers to a reference laboratory
      using Clinical and Laboratory Standards Institute susceptibility testing methods
      and interpretative criteria. Meropenem continued to demonstrate 1) high potency
      with MIC(90) values 4- to 16-fold lower than imipenem against the
      Enterobacteriaceae, 2) equal activity against Pseudomonas aeruginosa, 3) 2-fold
      less activity compared with imipenem against Acinetobacter spp., and 4) 4- to 8
      fold less activity compared with imipenem against the oxacillin-susceptible
      staphylococci. The wide spectrum of activity for carbapenems against
      Enterobacteriaceae (1657 strains) was confirmed by the overall rank order by
      percentage susceptibility at breakpoint criteria: imipenem (98.9%) > meropenem
      (98.7%) > cefepime (97.6%) > piperacillin/tazobactam (92.0%) > ceftriaxone
      (91.2%) > aztreonam (90.6%) > gentamicin = tobramycin (90.5%) > ceftazidime
      (90.4%) > levofloxacin (84.9%) > ciprofloxacin (83.9%). Against Acinetobacter
      spp. isolates, only tobramycin (92.0% susceptible) and carbapenems (92.0-85.6%)
      exhibited acceptable levels of activity. A continued increase in the resistance
      rate for both ciprofloxacin and levofloxacin was observed with highest rates
      found among indole-positive Proteae species (36.5-33.3%) and Escherichia coli
      (21.6-20.4%) isolates, some documented by molecular typing methods as clonally
      related. Ongoing surveillance of meropenem and other broad-spectrum antimicrobial
      agents appears warranted to monitor the potency and spectrum of activity against
      indicated Gram-negative and-positive pathogens causing serious infections in the
      hospital setting, and to detect the emergence of new or novel resistance
      mechanisms that could compromise clinical utility (serine and metallo
      carbapenemases).

PMID- 16949244
TI  - A PCR-based assay for detection of emerging vaccinia-like viruses isolated in
      Brazil.
AB  - We report 2 strategies to identify Brazilian vaccinia virus (VACV) isolates
      related to Cantagalo virus (CTGV) based on the amplification of the hemagglutinin
      (HA) gene by the polymerase chain reaction (PCR). One PCR protocol was combined
      with restriction analysis using the endonuclease SnaB I, generating a unique
      digestion pattern for CTGV amplicons. The restriction profile could identify 41
      CTGV-related isolates in 43 clinical specimens and clearly differentiated them
      from other orthopoxviruses and strains of VACV. Alternatively, we used a 1-step
      PCR assay with primers that specifically targeted CTGV HA sequence. This protocol
      produced similar results more rapidly than the 1st strategy, eliminating post-PCR
      procedures. The results were supported by Western blot analysis of the viral
      protein profile in infected cells. Both PCR-based methods enabled a fast,
      sensitive, and cost-effective detection of new isolates of VACV related to CTGV
      directly from clinical samples without requiring virus isolation.

PMID- 16949245
TI  - Antimicrobial activity of tigecycline against clinical isolates from Spanish
      medical centers. Second multicenter study.
AB  - The antimicrobial activity of tigecycline, a novel glycylcycline, was evaluated
      against 1102 bacterial isolates from 20 centers in Spain. The MIC of tigecycline
      at which 90% (MIC(90)) of the pneumococci tested were inhibited was the lowest
      (0.06 microg/mL) of all the antibiotics tested. The MICs of tigecycline against
      enterococci ranged from 0.03 to 0.125 microg/mL. All staphylococci were inhibited
      by < or =0.25 microg/mL of tigecycline, and 99.6% of Enterobacteriaceae isolates
      were inhibited by < or =2 microg/mL of tigecycline. Tigecycline demonstrated good
      activity against Bacteroides fragilis group organisms with an MIC(90) of 4
      microg/mL. The results of this study confirm the excellent activity of
      tigecycline against multiresistant Gram-positive and Gram-negative pathogens.

PMID- 16949246
TI  - Single, double and triple mutants of Salmonella enterica serovar Typhimurium degP
      (htrA), degQ (hhoA) and degS (hhoB) have diverse phenotypes on exposure to
      elevated temperature and their growth in vivo is attenuated to different extents.
AB  - DegP (HtrA) is a well-studied protease involved in survival of bacteria under
      stress conditions in vitro and in vivo. There are two paralogues of DegP in the
      Salmonella enterica serovar Typhimurium genome, DegQ and DegS. In order to
      understand more about the biological significance of this gene family, a series
      of deg-deletion mutants was generated in S. Typhimurium strain SL3261 by allelic
      replacement. At elevated temperature in vitro, the viability of degP and degS
      mutants was reduced when compared with the parent strain whereas the viability of
      a degQ mutant was not significantly affected. The viability of a double degP-degS
      mutant at elevated temperature was severely decreased when compared with the
      respective single mutants or, interestingly, with a triple degP-degQ-degS mutant.
      All the deg deletions were transduced into the mouse-virulent strain SL1344 and
      the resultant mutants were injected intravenously into BALB/c mice to test
      virulence. degP and degS single mutants and all combinations of double and triple
      mutants were attenuated to different degrees, whereas the single degQ mutant was
      as virulent as the wild-type strain. Thus, within this gene family, degP and degS
      appear important for survival at elevated temperature and are necessary for full
      virulence, whereas a single degQ deletion appears to have no clear role in
      survival and growth at elevated temperature or in mice.

PMID- 16949247
TI  - Shiitake (Lentinula edodes (Berkeley) Pegler) extracts as a modulator of
      micronuclei induced in HEp-2 cells.
AB  - Shiitake (Lentinula edodes (Berkeley) Pegler) is one of the most consumed
      mushrooms, for both therapeutic purposes and as food, therefore, the study of its
      biological properties is of great interest for producers and consumers. Aqueous
      extracts of the shiitake mushroom (L. edodes (Berkeley) Pegler) were evaluated by
      the micronucleus test (MN) in HEp-2 cells in vitro, to analyze their possible
      mutagenic and antimutagenic activities. None of the three extract concentrations
      tested (0.5, 1.0 and 1.5mg/mL) presented mutagenicity at any of the preparation
      temperatures (4 degrees C, 22+/-2 degrees C and 60 degrees C). In the
      antimutagenicity evaluation, all extract concentrations at all preparation
      temperatures presented a strong protective activity for the HEp-2 cells in
      response to the alkylating agent methyl methanesulfonate (MMS) in the different
      treatment protocols: pre-treatment, simultaneous treatment and post-treatment.
      The extracts prepared at 22+/-2 degrees C presented the lowest frequencies of MN
      in the evaluations of mutagenicity and antimutagenicity, indicating these as the
      best option for potential therapeutic use.

PMID- 16949248
TI  - Muscle relaxation therapy for anxiety disorders: it works but how?
AB  - Muscle relaxation therapy (MRT) has continued to play an important role in the
      modern treatment of anxiety disorders. Abbreviations of the original progressive
      MRT protocol [Jacobson, E. (1938). Progressive relaxation (2nd ed.). Chicago:
      University of Chicago Press] have been found to be effective in panic disorder
      (PD) and generalized anxiety disorder (GAD). This review describes the most
      common MRT techniques, summarizes recent evidence of their effectiveness in
      treating anxiety, and explains their rationale and physiological basis. We
      conclude that although GAD and PD patients may exhibit elevated muscle tension
      and abnormal autonomic and respiratory measures during laboratory baseline
      assessments, the available evidence does not allow us to conclude that
      physiological activation decreases over the course of MRT in GAD and PD patients,
      even when patients report becoming less anxious. Better-designed studies will be
      required to identify the mechanisms of MRT and to advance clinical practice.

PMID- 16949249
TI  - Selective mutism and anxiety: a review of the current conceptualization of the
      disorder.
AB  - Selective mutism (SM) is a rare and interesting condition that has been
      associated with a wide variety of childhood psychiatric conditions. Historically
      viewed as more of an oddity than a distinct diagnostic entity, early
      conceptualizations of the condition were based largely on case studies that
      tended to link SM with oppositional behavior. More recently, controlled studies
      have enhanced our understanding of SM. This review summarizes the current
      conceptualization of SM, highlighting evidence supporting the notion that SM is
      an anxiety-related condition.

PMID- 16949250
TI  - Fourteen novel human members of mitochondrial solute carrier family 25 (SLC25)
      widely expressed in the central nervous system.
AB  - Members of the solute carrier family 25 (SLC25) are known to transport molecules
      over the mitochondrial membrane. In this paper we present 14 novel members of
      SLC25 family in human. These were provided with following gene symbols by the
      HGNC: SLC25A32, SLC25A33, SLC25A34, SLC25A35, SLC25A37, SLC25A38, SLC25A39,
      SLC25A40, SLC25A41, SLC25A42, SLC25A43, SLC25A44, SLC25A45, and SLC25A46. We also
      identified the orthologues for these genes in rat and mouse. Moreover, we found
      yeast orthologues for 9 of these genes and show that the predicted substrate
      binding residues are highly conserved in the human and yeast proteins. We
      performed a comprehensive tissue localization study for 9 of these genes on a
      panel of 30 rat tissues with quantitative real-time polymerse chain reaction. We
      detected their mRNA in a wide number of tissues, both in brain and in periphery.
      This study provides an overall roadmap of the repertoire of the SLC25 family in
      mammals, showing that there are at least 46 genes in the human genome coding for
      mitochondrial transporters.

PMID- 16949251
TI  - Efficacy of propentofylline, a glial modulating agent, on existing mechanical
      allodynia following peripheral nerve injury.
AB  - Increasing evidence points to a role for spinal neuroimmune dysregulation (glial
      cell activation and cytokine expression) in the pathogenesis of chronic pain.
      Suppression of astrocytic and microglial activation with the methylxanthine
      derivative, propentofylline, pre-emptively attenuates the development of nerve
      injury-induced allodynia. Currently, we investigated the ability of systemic
      propentofylline to reverse existing, long-term allodynia after nerve injury--a
      clinically relevant paradigm. Rats received L5 spinal nerve transection or sham
      surgery and the development of mechanical allodynia was assessed daily for 2
      weeks, at which time injured rats exhibited robust responses to non-noxious von
      Frey filaments. On days 14-27, rats received either saline or 101 mg/kg
      propentofylline by intraperitoneal (i.p.) injection. On day 28 or 42 (after a 14
      day drug washout period), lumbar spinal cord sections were processed for
      assessment of astrocytic glial fibrillary acidic protein (GFAP) and microglial OX
      42 (antibody against CR3/CD11b). Propentofylline treatment to nerve injured rats
      resulted in significant reversal of allodynia that lasted throughout the 14-day
      washout period. Spinal microglial activation was observed at days 28 and 42 post
      injury at the protein level, in the absence of mRNA level changes. Less robust
      increases in GFAP immunoreactivity were observed at days 28 and 42 post
      transection. Interestingly, propentofylline treatment suppressed microglial
      activation at both time points in this paradigm. Taken together, our results
      highlight the clinical potential of the glial modulating agent, propentofylline,
      for the treatment of neuropathic pain as well as a role for microglia in the long
      term maintenance of allodynia.

PMID- 16949253
TI  - The emergence of goals in a self-organizing network: a non-mentalist model of
      intentional actions.
AB  - A model of intentional actions is presented through the operation of two
      connected neural networks. A deterministic causal recurrent network relates a
      random initial state to an ordered final state. A perceptron-like, feed-forward
      network provides a memory mechanism that links the final states to the original
      initial states. A non-supervised learning mechanism that selects which final
      states are defined as goals to be retrieved together with initial states leading
      to them. Causal sequences of states are transformed into procedures directed
      towards the achievements of goals. We propose a mechanism through which goals and
      their achievement in goal-directed actions can be emerging properties of self
      organizing networks, not initially endowed with intentionality. This allows for a
      monist, non-mentalist description which does not need to resort to intentional
      mental states as causes of intentional actions. Cognitive, neurophysiological and
      philosophical implications are discussed.

PMID- 16949254
TI  - Role of Src in angiopoietin 1-induced capillary morphogenesis of endothelial
      cells: Effect of chronic hypoxia on Src inhibition by PP2.
AB  - Signal transduction pathways leading to angiopoietin 1 (Ang1)-induced capillary
      morphogenesis by endothelial cells remain poorly defined. Angiogenic cellular
      responses by endothelial cells may be modulated in vivo by chronic hypoxia, such
      as that induced by tumors. Here, we studied Ang1-induced capillary morphogenesis
      in human umbilical-vein endothelial cells (HUVECs) cultured chronically under
      normoxic (21% oxygen) or hypoxic (1.5% oxygen) conditions. Downregulation of Src
      using a small interfering RNA (siRNA) inhibited Ang1-induced capillary
      morphogenesis of HUVECs cultured under both conditions by blocking cell spreading
      and protrusion. Ang1 upregulated the Src-dependent secretion of vascular
      endothelial growth factor-A (VEGF-A). Blockade of endogenous VEGF-A also
      inhibited Ang1-induced capillary morphogenesis. Addition of exogenous VEGF-A
      restored cell spreading and protrusion, leading to Ang1-induced capillary
      morphogenesis of Src siRNA-treated HUVECs, suggesting that Ang1-induced VEGF-A
      secretion through Src was required for capillary morphogenesis. PP2 inhibited
      both Ang1-induced capillary morphogenesis and Src activation in HUVECs cultured
      under normoxic conditions, but the PP2 activity was significantly impaired in
      HUVECs cultured under hypoxic conditions. Expression of multidrug resistance
      associated protein 1 (MRP 1) was upregulated in hypoxic HUVECs, and treatment
      with MRP 1 siRNA restored the inhibitory action of PP2. Taken together, our
      results suggest that Ang1 induces capillary morphogenesis in HUVECs through Src
      dependent upregulation of endogenous VEGF-A. Conditions of chronic hypoxia
      impaired the effect of PP2, possibly via MRP 1.

PMID- 16949252
TI  - Weighing up the benefits of work: behavioral and neural analyses of effort
      related decision making.
AB  - How we decide whether a course of action is worth undertaking is largely unknown.
      Recently, neuroscientists have been turning to ecological approaches to address
      this issue, examining how animals evaluate the costs and benefits of different
      options. We present here evidence from rodents and monkeys that demonstrate the
      degree to which they take into account work and energetic requirements when
      deciding what responses to make. These calculations appear to be critically
      mediated by the anterior cingulate cortex (ACC) and mesolimbic dopamine (DA)
      pathways, with damage to either causing a bias towards options that are easily
      obtained but yield relatively smaller reward rather than alternatives that
      require more work but result in greater reward. The evaluation of such decisions
      appears to be carried out in systems independent of those involved in delay
      discounting. We suggest that top-down signals from ACC to nucleus accumbens (NAc)
      and/or midbrain DA cells may be vital for overcoming effort-related response
      costs.

PMID- 16949255
TI  - Role of Langerhans cells in cutaneous protective immunity: is the reappraisal
      necessary?
AB  - Langerhans cells (LC) are constantly exposed to external antigens and pathogens,
      and they are the cutaneous counterpart of dendritic cells (DC). DC not only act
      as professional antigen presenting cells to induce antigen-specific T cells for
      adaptive immune responses, but they also initiate a cascade of innate immune
      responses by sensing these danger signals. However, recent studies challenge the
      classical paradigm to position LC in the center of cutaneous immunity. Although
      LC express toll-like receptors (TLRs) that recognize bacterial and viral
      products, exposure to pathogen-associated TLR ligands triggers neither sufficient
      LC maturation nor good production of cytokines and chemokines. LC also lack the
      ability to produce IFN-gamma by any stimuli, and together with the
      characteristics of LC that are prone to produce Th2-type chemokines and to
      produce much less IL-12 in the presence of keratinocyte-derived GM-CSF, LC
      primarily may not have the character to induce Th1- and Tc1-type immune responses
      necessary for protective cellular immunity. Moreover, LC maturation is inhibited,
      rather than enhanced, by type I IFNs that are abundantly produced in viral
      infections in the skin microenvironment. Finally, recent data suggest that LC may
      not directly present viral antigens to T cells for their activation in mouse
      models of cutaneous viral infection. The alternative player in protective immune
      responses may be surrounding keratinocytes, which may modulate LC functions
      indirectly. Dermal DC may also participate in this scheme. Further studies are
      required to clarify the role of LC in their interplay with keratinocytes and
      other DC subsets, and to draw the entire picture of the cutaneous immune system
      against pathogens.

PMID- 16949256
TI  - Discordance of meropenem versus imipenem activity against Acinetobacter
      baumannii.

PMID- 16949257
TI  - CTX-M-37 in Salmonella enterica serotype Isangi from Durban, South Africa.
AB  - Beta-lactamase-mediated resistance was investigated in 59 putative extended
      spectrum beta-lactamase (ESBL)-positive Salmonella spp. from the paediatric ward
      of a tertiary hospital in Durban, South Africa. Three Salmonella enterica
      serotype Isangi cultured from stool samples were multidrug resistant, with
      susceptibility only to meropenem, piperacillin/tazobactam and cefoxitin.
      Isoelectric focusing revealed beta-lactamases with isoelectric points of pI 5.8,
      6.8 and 7.2. Sequencing identified beta-lactamases CTX-M-37 and TEM-1. To our
      knowledge, this is the first report of CTX-M-37 from S. enterica serotype Isangi
      in South Africa.

PMID- 16949258
TI  - Molecular epidemiology of antimicrobial resistance among Salmonella enterica
      serovar Infantis from poultry in Kagoshima, Japan.
AB  - Antimicrobial susceptibility and resistance genes of 135 strains of Salmonella
      enterica serovar Infantis isolated from poultry in Kagoshima were examined. One
      strain (0.7%) was resistant to ampicillin (A), 97% to streptomycin (S), 95.6% to
      sulphamethoxazole (Su), 96.3% to oxytetracycline (T), 11.1% to kanamycin (Km) and
      36.3% to ofloxacin (O). Multiresistant phenotypes identified were ASSuT-Km, SSuT
      Km, SSuT-O and SSuT. Class 1 integrons were detected in 94.8% of isolates.
      Approximately 89% of oxytetracycline-resistant strains carried the tetA gene and
      all of the 131 streptomycin-resistant isolates carried the aadA1a gene. Forty
      percent of kanamycin-resistant isolates carried the aphA1-Iab gene. All isolates
      were susceptible to chloramphenicol. Recognition of TEM-type beta-lactamase in a
      S. Infantis strain from chickens is a recent rare finding in Japan.

PMID- 16949259
TI  - Automated ROI-based brain parcellation analysis of frontal and temporal brain
      volumes in schizophrenia.
AB  - Structural MRI studies of schizophrenia have yielded a diversity of findings. To
      help characterize regional gray matter changes in schizophrenia, we used an
      automated region of interest (ROI)-based approach that targeted frontal and
      temporal regions in schizophrenia patients. The sample compromised 43
      schizophrenia patients (21 chronic patients, 22 unmedicated first episode
      patients), 20 first episode non-schizophrenia psychosis patients and 47
      comparison subjects. Automated regional volume measurement was performed in 22
      ROIs, including frontal and temporal cortical subregions and hippocampus.
      Correlations between volume measures, duration of illness and clinical scores
      were evaluated. Chronic schizophrenia patients showed gray matter volume
      differences in left dorsolateral prefrontal cortex (DLPFC) and right
      supplementary motor area (SMA). First episode psychosis patients presented
      smaller right anterior cingulate cortex (ACC) and left DLPFC than comparison
      subjects. Disorganization scores and duration of illness correlated negatively
      with gray matter volume of DLPFC and SMA in chronic schizophrenia patients. Using
      an automated ROI-based method, we found volume reductions in lateral and medial
      frontal regions in both first episode and chronic schizophrenia. The automated
      ROI-based method can be used as a valid and efficient tool for quantification of
      regional gray matter volume in schizophrenia in multiple ROIs across the brains
      of large numbers of subjects.

PMID- 16949260
TI  - 31P double-quantum solid-state NMR study of phosphoroorganic compounds with (O)P
      O-P-(O), (S)P-O-P(S) and (S)P-S-P(O) unit.
AB  - In this work we have tested applicability of the commonly used double quantum
      recoupling sequence POST-C7 to study of (31)P-(31)P geometrical constraints for
      phosphoroorganic model compounds with different chemical shift anisotropy (CSA)
      and distinct molecular dynamics in the crystal lattice. Our results clearly show
      that even with large CSA, POST-C7 gives good efficiency of (31)P double-quantum
      excitations. Moreover, large amplitude molecular motion only slightly disturb
      (31)P build-up curve. Chi(2) error analysis is used for verification of values
      and orientations of chemical shift tensors (CST) parameters employed for
      simulation of POST-C7 buildup curves.

PMID- 16949261
TI  - [Genetic predisposition and children infectious disease].
AB  - The classic primary immunodeficiencies confer predisposition to multiple
      infectious diseases. However since ten years severe pediatric infections which
      were idiopathic have now molecular explanation. Indeed, defects in several genes
      confer a predisposition to infection with specific pathogenes in otherwise
      healthy individuals. These children present a new kind of hereditary
      immunodeficiency with severe and/or recurrent infections caused by only one
      microorganisms family, in opposition of others patients with "classic" primary
      immunodeficiency.

PMID- 16949262
TI  - A new expert systems (SeDeM diagram) for control batch powder formulation and
      preformulation drug products.
AB  - The new SeDeM Method is proposed for testing the batch-to-batch reproducibility
      of the same active pharmaceutical ingredient (API) in powder form. The procedure
      describes the study of the galenic properties of substances in powder form in
      terms of the applicability of direct compression technology. Through experimental
      determination of the SeDeM Method parameters, and their subsequent mathematical
      treatment and graphical expression (SeDeM Diagram), three batches of the same API
      were analysed to determine whether it was suitable for direct compression. Batch
      to-batch reproducibility of the results was verified. It was concluded that the
      SeDeM Method is suitable for testing batch-to-batch reproducibility of
      characteristics in powdered APIs substances. The results obtained confirm that
      the SeDeM Method is a useful, effective tool for drug-preformulation studies
      providing the pharmacotechnical data required when formulating a drug in tablet
      form. In addition, the results were effective for defining the most appropriate
      manufacturing technology.

PMID- 16949263
TI  - Role of omega-3 fatty acids in brain development and function: potential
      implications for the pathogenesis and prevention of psychopathology.
AB  - The principle omega-3 fatty acid in brain, docosahexaenoic acid (DHA),
      accumulates in the brain during perinatal cortical expansion and maturation.
      Animal studies have demonstrated that reductions in perinatal brain DHA accrual
      are associated with deficits in neuronal arborization, multiple indices of
      synaptic pathology including deficits in serotonin and mesocorticolimbic dopamine
      neurotransmission, neurocognitive deficits, and elevated behavioral indices of
      anxiety, aggression, and depression. In primates and humans, preterm delivery is
      associated with deficits in fetal cortical DHA accrual, and children/adolescents
      born preterm exhibit deficits in cortical gray matter maturation, neurocognitive
      deficits particularly in the realm of attention, and increased risk for attention
      deficit/hyperactivity disorder (ADHD) and schizophrenia. Individuals diagnosed
      with ADHD or schizophrenia exhibit deficits in cortical gray matter maturation,
      and medications found to be efficacious in the treatment of these disorders
      increase cortical and striatal dopamine neurotransmission. These associations in
      conjunction with intervention trials showing enhanced cortical visual acuity and
      cognitive outcomes in preterm and term infants fed DHA, suggest that perinatal
      deficits in brain DHA accrual may represent a preventable neurodevelopmental risk
      factor for the subsequent emergence of psychopathology.

PMID- 16949264
TI  - Randomised trial comparing as-needed versus regular treatment with formoterol in
      patients with persistent asthma.
AB  - PURPOSE: The aim of this study was to demonstrate the equivalent efficacy of
      inhaled formoterol in asthmatic patients, either given as-needed or on a regular
      twice-daily schedule. METHODS: Randomised, open 12-week study in patients with
      mild to moderate asthma not adequately controlled with inhaled
      glucocorticosteroids alone. Patients received inhaled formoterol as needed or on
      a regular schedule (2x2 puffs/day with 6 microg formoterol per puff). Patients in
      the twice-daily formoterol group could use salbutamol as a rescue medication. The
      primary endpoint was the number of patients with asthma exacerbations in each
      group. RESULTS: Thirty-nine centres randomised 359 patients. The number of
      patients with asthma exacerbations showed neither a clinically relevant nor a
      statistically significant difference between groups: formoterol as-needed: 3.95%
      (7 of 177); twice daily: 3.45% (6 of 174). Patients in the formoterol as-needed
      group used significantly less formoterol (-1.5 puffs per day; P<0.0001).
      Including the saved rescue medication (up to one puff per day), total beta-2
      agonist use in the formoterol as-needed group decreased by approximately 2-2.5
      puffs per day. Both formoterol treatment schedules were well tolerated.
      Musculoskeletal pain and tremor were less frequent in the formoterol as-needed
      group: headaches were slightly more frequent. CONCLUSION: Formoterol given as
      needed and without additional beta-2 agonist, and formoterol given on a regular
      basis twice daily, supplemented by salbutamol as a rescue medication, appeared
      equally effective in this clinical study. Drug consumption was markedly lower in
      the former group.

PMID- 16949265
TI  - Evaluation of male COPD patients' health status by proxies.
AB  - BACKGROUND: It is not always possible to collect information about health from
      patients, so information from proxies (relatives and others) is used to aid
      medical decision-making, but there has been no formal evaluation of the
      reliability of their reports. The aim of this study was to analyse the
      reliability and validity of the St. George's Respiratory Questionnaire (SGRQ)
      answered by proxies and to determine their accuracy as raters. METHODS: Stable
      symptomatic male COPD patients and relatives living in the same house
      independently completed the same version of the SGRQ. RESULTS: Forty-six male
      patients were studied; age 72.1+/-7.3 years, pre-bronchodilator FEV(1) 37.9+/
      14.7% predicted, 30.4% on long-term oxygen therapy. Internal consistency
      (Cronbach's alpha) was over 0.73 for all domains and >0.9 for the total score.
      Their scores correlated with dyspnoea (r=0.30-0.45) and FEV(1) (r=0.4-0.61). The
      proxies could distinguish between levels of disease severity, but with a weaker
      discriminant power compared to patients. Seventy-two per cent of proxies over
      reported the degree of the patient's overall health status impairment, especially
      at mild-moderate scores. Proxies showed weaker correlations at the more severe
      scores. CONCLUSIONS: The SGRQ was reliable and valid when administered to
      relatives of male COPD patients; however due to the systematic over-reporting of
      the level of the patient's health status impairment, caution should be applied
      whilst trying to use proxies as surrogates for male COPD patients.

PMID- 16949266
TI  - Management of asthma with anti-immunoglobulin E: a review of clinical trials of
      omalizumab.
AB  - Immunoglobulin E (IgE) is a key mediator of the inflammatory reactions that are
      central to the pathogenesis of allergic diseases such as asthma and rhinitis. The
      recognition of the importance of IgE in allergic disease led to the development
      of omalizumab, a humanized monoclonal anti-IgE antibody that binds free
      circulating IgE and prevents the interaction between IgE and high-affinity
      (FcepsilonRI) and low-affinity (FcepsilonRII) IgE receptors on inflammatory
      cells. By removing free IgE, omalizumab also markedly downregulates the
      expression of high-affinity receptors on basophils, mast cells and dendritic
      cells. Several studies have shown that omalizumab effectively reduces the risk of
      exacerbations and hospitalization and improves symptom control, lung function and
      quality of life in patients with severe persistent allergic asthma. Importantly,
      omalizumab has been shown to be effective in patients with poorly controlled
      severe persistent allergic asthma, a group of patients with few effective
      additional treatment options. In addition, omalizumab has been shown to provide
      effective relief from the symptoms of allergic rhinitis (including patients with
      concomitant asthma). Patients with uncontrolled severe persistent allergic asthma
      are a challenging and difficult-to-treat population for whom omalizumab might
      represent an important new treatment option. In addition, omalizumab may provide
      a means to address comorbid allergic disease in patients with asthma. Further
      investigation is also warranted to explore potential applications of omalizumab
      in occupational asthma.

PMID- 16949267
TI  - Hybridisation of surface-immobilised single-stranded oligonucleotides and polymer
      monitored by surface plasmon resonance.
AB  - We have investigated the hybridisation of thiol-modified single-stranded DNA
      embedded in a polyacrylamide layer through the technique of surface plasmon
      resonance (SPR). Kinetic studies were carried out by two different immobilisation
      methods: (a) SH-ssDNA was firstly attached on gold and the remaining free space
      was filled with polymer and (b) SH-ssDNA and the polymer was attached onto the
      surface from the same solution. The immobilisation methods were compared for
      various concentrations of SH-ssDNA. Hybridisation was dependent on both the
      immobilisation method and the concentration of the components. The highest
      hybridisation was obtained when SH-ssDNA and the polymer was immobilised from the
      same solution at low SH-ssDNA concentration or when high concentrations of oligos
      were spread onto the surface and the surface was post-treated with polymer. The
      target response corresponded to a surface coverage of 100+/-15 ng/cm2. The same
      surface coverage on hybridisation was also obtained when low concentration of SH
      ssDNA and polymer was attached onto the surface from the same solution. The non
      specific binding of sample DNA was very low at optimal concentrations due to the
      polymer and the hybridisation was linearly dependent on target concentration.

PMID- 16949268
TI  - Optical forward-scattering for detection of Listeria monocytogenes and other
      Listeria species.
AB  - We demonstrate here the development of a non-invasive optical forward-scattering
      system, called 'scatterometer' for rapid identification of bacterial colonies.
      The system is based on the concept that variations in refractive indices and
      size, relative to the arrangement of cells in bacterial colonies growing on a
      semi-solid agar surface will generate different forward-scattering patterns. A
      1.2-1.5mm colony size for a 1mm laser beam and brain heart infusion agar as
      substrate were used as fixed variables. The current study is focused on exploring
      identification of Listeria monocytogenes and other Listeria species exploiting
      the known differences in their phenotypic characters. Using diffraction theory,
      we could model the scattering patterns and explain the appearance of radial
      spokes and the rings seen in the scattering images of L. monocytogenes. Further,
      we have also demonstrated development of a suitable software for the extraction
      of the features (scalar values) calculated from images of the scattering patterns
      using Zernike moment invariants and principal component analysis and were grouped
      using K-means clustering. We achieved 91-100% accuracy in detecting different
      species. It was also observed that substrate variations affect the scattering
      patterns of Listeria. Finally, a database was constructed based on the scattering
      patterns from 108 different strains belonging to six species of Listeria. The
      overall system proved to be simple, non-invasive and virtually reagent-less and
      has the potential for automated user-friendly application for detection and
      differentiation of L. monocytogenes and other Listeria species colonies grown on
      agar plates within 5-10 min analysis time.

PMID- 16949269
TI  - Diclofenac and post-partum haemorrhage.

PMID- 16949270
TI  - Resident training in obstetric anesthesia in the United States.
AB  - BACKGROUND: Limited information exists on obstetric anesthesia experience and
      training within residency training programs in the United States. METHODS: A
      survey was sent to every academic anesthesiology training program in the United
      States (n=120), with follow-up reminders to non-responders. The survey included
      14 questions divided into staffing, didactic teaching and epidemiology regarding
      the practice of obstetric anesthesia at each academic institution. RESULTS: A
      response rate of 78% (93/120) was achieved. The returned surveys were grouped
      into three tiers by the number of deliveries/year from the lowest (Group 1) to
      the highest (Group 3). The total number of obstetric deliveries at each
      institution ranged from 340 to 15 800. The average number of residents/month
      rotating on obstetric anesthesia was 2.6 and the number of months spent on the
      obstetric anesthesia service was 2.7. The average number of obstetric anesthesia
      lectures given was 12 per month. A total of 21.5 obstetric anesthesia fellows
      were reported to train at these institutions, with fellows being more common in
      larger institutions. Group 1 institutions were more likely to have
      anesthesiologists covering the main operating room and obstetric suite
      simultaneously. The average number of obstetric anesthesia staff
      members/institution was 4.3. The average cesarean section rate was 27.8%, with
      5.8% being performed under general anesthesia. Neuraxial techniques were used in
      an average of 70.3% of laboring parturients, with combined spinal epidurals
      accounting for 24.6% of the techniques. CONCLUSION: The average number of
      obstetric deliveries per year for institutions with a resident training program
      was 3498+/-2383. Dedicated obstetric anesthesia staffing was more common when
      >3700 deliveries/year were performed; the presence of this staffing corresponded
      with a reduction in the use of general anesthesia for cesarean deliveries. Few
      differences in the resident lecture didactic exposure were observed in terms of
      numbers of lectures and months on the obstetric anesthesia service, although a
      significantly greater number of clinical cases was available to each resident in
      those institutions with greater overall numbers of obstetric cases.

PMID- 16949271
TI  - Cesarean delivery on maternal request: implications for anesthesia providers.

PMID- 16949272
TI  - Injectate temperature and discomfort during epidural injection.

PMID- 16949273
TI  - Impact of changing from ephedrine to phenylephrine as the first-line vasopressor
      during urgent caesarean section.

PMID- 16949274
TI  - Women should be told ALL risks before regional anaesthesia is performed.

PMID- 16949275
TI  - At caesarean section under regional anaesthesia, it is essential to test sensory
      block with light touch before allowing surgery to start.

PMID- 16949276
TI  - Transcranial magnetic stimulation, causal structure-function mapping and networks
      of functional relevance.
AB  - Transcranial magnetic stimulation is now a well-established tool for inducing
      transient changes in brain activity non-invasively in conscious human volunteers.
      During the past couple of years, the ability to actively interfere with neural
      processing during behavioral performance has been used increasingly for the
      investigation of causal brain-behavior relationships in higher cognitive
      functions. The simultaneous combination of transcranial magnetic stimulation with
      methods of functional brain imaging, however, promises to be of especially great
      value for our understanding of the human brain, as it provides the opportunity to
      stimulate brain circuits while simultaneously monitoring changes in brain
      activity and behavior. Such an approach could help us to identify brain networks
      of functional relevance, and might enable causal brain-behavior inferences across
      the entire brain.

PMID- 16949277
TI  - Short term psychological distress in patients actively approached for genetic
      counselling after diagnosis of breast cancer.
AB  - This prospective study assessed anxiety, depression and breast cancer-specific
      distress in recently diagnosed breast cancer patients before and after an active
      approach for genetic counselling at the beginning of adjuvant radiotherapy (mean:
      52 days after surgery). Patients completed the hospital anxiety and depression
      scale (HADS) and the impact of event scale (IES). Psychological distress did not
      increase after the approach. High anxiety decreased in the comparison group
      (n=182), whereas breast cancer specific distress decreased in the approached
      group (n=220). It is concluded that breast cancer patients can be approached for
      genetic counselling shortly after surgery without additional short-term
      psychological burden. Patients who are young, single with little social support,
      less optimistic, use an avoiding coping style, experience a lower quality of life
      or who are highly distressed prior to approach for genetic counselling, need
      extra attention. Medical history did not prove to be relevant.

PMID- 16949278
TI  - Contamination of surface run-off water and soil in two horse paddocks.
AB  - Increased stabling of horses near to cities has led to interest in the
      environmental effects of paddocks. In this study, the contamination of horse
      paddocks was examined by determining the nutrient and micro-organism contents in
      the surface run-off waters and the electrical conductivity, pH and phosphorus,
      potassium and nitrate contents of top soils. Two open-stable paddocks were
      studied, one cleaned and the other left uncleaned, with a stocking density of
      37.5 animalsha(-1) in both. The feeding and drinking places were the most
      contaminated areas of both paddocks. In spring, after seven months of use, the
      nutrient concentrations in the surface run-off water from paddocks were 3.4
      18.8mg/l for total phosphorus, 3.0-15.0mg/l for phosphate and 18.3-140.0mg/l for
      total nitrogen, indicating a risk to surface waters. Summer rain generated
      surface run-off, especially from the feeding area of the stock-free uncleaned
      paddock.

PMID- 16949279
TI  - Physiological characterization of Dunaliella sp. (Chlorophyta, Volvocales) from
      Yucatan, Mexico.
AB  - Physiological responses of Dunaliella salina and Dunaliella viridis, isolated
      from solar saltworks on the Yucatan Peninsula, were studied. Optimal growth
      temperature for D. salina was 22 degrees C (3.06 x 10(6) cells mL(-1)) and 26
      degrees C for D. viridis (4.04 x 10(6)cells mL(-1)). Total carotenoid content in
      D. salina increased with temperature to a maximum of 35.14 pg cell(-1) at 38
      degrees C. Dunaliella salina alpha-carotene and beta-carotene content was 0.083+/
      0.003 and 0.598+/-0.020 mg 100g dry wt(-1) respectively, whereas lower values
      were found in D. viridis cultured under same experimental conditions (0.018+/
      0.002 and 0.136+/-0.012 mg 100g dry wt(-1) respectively). The highest specific
      growth rate in D. salina was obtained at 10% NaCl (0.28 d(-1)), while its cell
      volume increased from 524 to 2066.93 microm(3) when cultured from 10% to 35%
      NaCl. Maximum photosynthetic rates were attained when increasing from optimal
      growing temperature to 30 degrees C for D. viridis (108 n mol O(2)microg chl
      alpha h(-1)) and D. salina (139 n mol O(2)microg chl alpha h(-1)). Photosynthetic
      responses to temperature variations indicated physiological adjustments in both
      species, with higher acclimation in D. salina. Evaluation of physiological
      attributes of these species will be used for to carry out mass cultivation.

PMID- 16949280
TI  - The performance of a phase separated granular bed bioreactor treating brewery
      wastewater.
AB  - This study presents the performance characteristics of a plug flow phase
      separated anaerobic granular bed baffled reactor (GRABBR) fed with brewery
      wastewater at various operating conditions. The reactor achieved chemical oxygen
      demand (COD) removal of 93-96% with high methane production when operated at
      organic loading rates (OLRs) of 2.16-13.38kg COD m(-3)d(-1). The reactor
      configuration and microbial environment encouraged the acidogenic dominant zone
      to produce intermediate products suitable for degradation in the predominantly
      methanogenic zone. Noticeable phase separation between acidogenesis and
      methanogenesis mainly occurred at high OLR, involving a greater number of
      compartments to contribute to wastewater treatment. The highly active nature and
      good settling characteristics of methanogenic granular sludge offered high
      biomass retention and enhanced methanogenic activities within the system. The
      granular structure in the acidogenic dominant zone of the GRABBR was susceptible
      to disintegration and flotation. Methanogenic granular sludge was a multi-layered
      structure with Methanosaeta-like organisms dominant in the core.

PMID- 16949281
TI  - Effects of alpha-substitutions on structure and biological activity of anticancer
      chalcones.
AB  - Chalcones are known to exhibit antimitotic properties caused by inhibition of
      tubulin polymerisation. We describe here the effects of different alpha
      substitutions, in particular alpha-fluorination, on the structure and biological
      activity of a series of chalcones.

PMID- 16949282
TI  - Synthesis of 3,6-bis[H-Tyr/H-Dmt-NH(CH2)m,n]-2(1H)pyrazinone derivatives:
      function of alkyl chain length on opioid activity.
AB  - Dimeric opioid analogues linked to a pyrazinone platform, 3-[Tyr/Dmt-NH(CH2)m]-6
      [Tyr/Dmt-NH(CH2)n]-2(1H)-pyrazinone (m, n=3 or 4), were synthesized. The Tyr
      containing compound (m=4, n=3) exhibited mu-receptor affinity (K(i)mu; 7.58 nM)
      comparable to that of morphine, while the Dmt derivatives exhibited considerably
      higher affinity (K(i)mu; 0.021-0.051 nM) with corresponding agonism (IC50=1.79
      4.93 nM). Interestingly one compound (m=4, n=3) revealed modest delta-opioid
      agonism; the converse analogue (m=3, n=4), however, was inactive in MVD assay.

PMID- 16949283
TI  - Naphtho[2,3-b][1,4]-thiazine-5,10-diones and 3-substituted-1,4-dioxo-1,4
      dihydronaphthalen-2-yl-thioalkanoate derivatives: synthesis and biological
      evaluation as potential antibacterial and antifungal agents.
AB  - A series of 3-substituted-1,4-dioxo-1,4-dihydronaphthalen-2-yl-thio-alkanoate
      derivatives 3-21 and naphtho[2,3-b][1,4]-thiazine-5,10-diones 24 were synthesized
      and evaluated for their antibacterial and antifungal activities. The structure
      activity relationships of these compounds were studied and the results show that
      the compound 24a exhibited better antibacterial activity than Gentamycin in vitro
      against Staphylococcus aureus. In addition 24a also imparted marked antifungal
      activity in vitro against Cryptococcus neoformans, Sporothrix schenckii, and
      Trichophyton mentagraphytes when compared with Fluconazole. Compounds 15, 18, 19,
      and 21 also exhibited significant antibacterial activity in vitro against S.
      aureus.

PMID- 16949284
TI  - The synthesis and SAR of 2-amino-pyrrolo[2,3-d]pyrimidines: a new class of Aurora
      A kinase inhibitors.
AB  - A new class of Aurora-A inhibitors have been identified based on the 2-amino
      pyrrolo[2,3-d]pyrimidine scaffold. Here, we describe the synthesis and SAR of
      this novel series. We report compounds which exhibit nanomolar activity in the
      Aurora-A biochemical assay and are able to inhibit tumor cell proliferation. This
      study culminates in compound 30, an inhibitor with potent activity against Aurora
      A (IC50=0.008 microM), anti-proliferative activity against several tumor cell
      lines and induces polyploidy in H460 cells.

PMID- 16949285
TI  - Solid-phase combinatorial approach for the optimization of soluble epoxide
      hydrolase inhibitors.
AB  - A 192-member library of N,N'-disubstituted urea inhibitors was synthesized by a
      solid-phase method. The ureas were tested for their inhibitory activities against
      recombinant human soluble epoxide hydrolase. Simple carbocyclic or para/meta
      substituted phenyl groups showed inhibition potencies that were equal to or
      greater than adamantane-based sEH inhibitors, while the presence of bulky or
      ionizable groups close to the urea group dramatically decreased their activities.

PMID- 16949286
TI  - Big gulps: specialized membrane domains for rapid receptor-mediated endocytosis.
AB  - Eukaryotic cells are well known to use an elaborate, clathrin-based endocytic
      machinery to internalize ligand-receptor complexes. Although the number of
      components identified as being used during this essential process has increased
      substantially over the past decade, an appreciation for how receptor-mediated
      endocytosis is organized at a broader, cellular scale is still mostly undefined.
      Here, some new insights into how cells cluster and organize the endocytic
      machinery at defined cytoplasmic domains to increase the speed and efficiency of
      ligand-receptor internalization are presented.

PMID- 16949287
TI  - Intra-endosomal membrane traffic.
AB  - Following endocytosis, ubiquitinated signaling receptors are incorporated within
      intraluminal vesicles of forming multivesicular endosomes. These vesicles then
      follow the pathway from early to late endosomes, remaining within the endosomal
      lumen, and are eventually delivered to lysosomes, where they are degraded
      together with their protein cargo. However, intraluminal vesicles do not always
      end up in lysosomes for degradation; they can also fuse back with the limiting
      membrane of late endosomes. This route, which might be regulated by lyso
      bisphosphatidic acid and its putative effector Alix, can be hijacked by the
      anthrax toxin and vesicular stomatitis virus and is presumably exploited by
      proteins and lipids that transit through intraluminal vesicles. Alternatively,
      these vesicles can be released extracellularly, like HIV in macrophages, upon
      fusion of endosomes or lysosomes with the plasma membrane.

PMID- 16949288
TI  - Critical care outreach: the need for effective decision-making in clinical
      practice (part 2).
AB  - As the extension of nursing into roles previously within the domain of medicine
      and the demand for evidence based practice continue to increase, the quality of
      decision making becomes imperative. Making accurate decisions is essential, both
      for the practitioner and for the patient, especially in the provision of critical
      care outreach (CCOR), to improve outcomes of care. With changes in health care
      delivery and increased accountability for practitioners' decisions, it is
      important to understand more about how clinical decisions are made and what
      factors influence them in order to inform practice. The previous paper outlined
      the theoretical background of clinical decision making and the knowledge that
      underpins practice in CCOR. In this paper, the authors, a Nurse Consultant in
      CCOR and a research fellow, examine the process of a practitioner's decision
      making in the practice of CCOR, through a collaborative reflective account of a
      case study. From this, recommendations are made about the future development of
      CCOR practitioners and services.

PMID- 16949289
TI  - Critical care outreach: the need for effective decision-making in clinical
      practice (Part 1).
AB  - Since the publication of 'Comprehensive Critical Care' (2000) critical care
      outreach (CCOR) services have been developed to meet the needs of patients
      through critical care provision 'without walls'. Now embedded nationally, CCOR is
      a central part of health care delivery in the National Health Service (NHS). To
      date, approximately 75% of hospitals in England have introduced and developed the
      service according, at least to some extent, to local needs and resources. While
      this has resulted in a somewhat inconsistent approach to the development and
      configuration of these services, a number of common elements remain. Arguably,
      effective clinical decision-making by CCOR practitioners is fundamental to
      efficient patient care management and the success of these services. In its
      examination of CCOR service provision this, the first of two papers, addresses
      the theoretical background of clinical decision making and the knowledge that
      underpins practice in CCOR. In the second paper, through collaborative reflection
      and analysis of a case study, the authors bring these together in a process that
      illuminates the realities of clinical decision making for CCOR practitioners.
      From this, recommendations are made about the future development of CCOR
      practitioners and services.

PMID- 16949290
TI  - Synthesis, tuberculosis inhibitory activity, and SAR study of N-substituted
      phenyl-1,2,3-triazole derivatives.
AB  - The aim of this work was to describe the synthesis, the in vitro anti
      Mycobacterium tuberculosis profile, and the structure-activity relationship (SAR)
      study of new N-substituted-phenyl-1,2,3-triazole-4-carbaldehydes (3a-l). The
      reactions of aromatic amine hydrochlorides with diazomalonaldehyde (1) produced
      several N-substituted-phenyl-1,2,3-triazole-4-carbaldehydes (3a-l) in moderate-to
      good yields. In order to investigate the influence of the difluoromethylene group
      on the anti-Mycobacterium activity of these compounds, fluorination of triazoles
      with DAST converted the corresponding carbaldehyde compounds into new
      difluoromethyl derivatives (4a-l) in excellent yield. Characterization of all
      compounds was achieved by spectroscopic means and additional for 1-(4
      methylphenyl)-1,2,3-triazole-4-carbaldehyde, 3k by X-ray crystallography.
      Compounds (3a-l) and (4a-l) have been screened for the inhibitory activity
      against Mycobacterium tuberculosis H37Rv strain (ATCC 27294) and all of them were
      able to inhibit the growth of the bacterium. Interestingly, 3a and 3k exhibited
      the best inhibition with MIC values of 2.5mug/mL, similar to pharmaceuticals
      currently used in the treatment of tuberculosis. Our SAR study indicated the
      importance of the hydrogen bond acceptor subunit (3a-l), the position in the
      aromatic ring, the planarity of triazole and phenyl rings in these compounds, and
      a correlation between the uniform HOMO coefficient distribution and the anti
      tubercular activity. The significant activity of 3a and 3k pointed them as
      promising lead molecules for further synthetic and biological exploration.

PMID- 16949291
TI  - Evaluation of 99mTc(CO)3 complex of 2-methyl-5-nitroimidazole as an agent for
      targeting tumor hypoxia.
AB  - An iminodiacetic acid (IDA) derivative of 2-methyl-5-nitroimidazole was
      synthesized as a carrier molecule for radiolabeling with the gamma emitting
      radioisotope, 99mTc, for imaging hypoxic regions of tumors. The ligand was
      synthesized in excellent yield and labeled using freshly prepared
      [99mTc(CO)3(H2O)3]+ intermediate. A complexation yield of over 95% could be
      achieved under mild conditions using a ligand concentration of 1 mg/mL [
      approximately 3 x 10(-3)M]. The complex was characterized by HPLC and its
      stability in human serum was studied. Biodistribution studies performed in Swiss
      mice bearing fibrosarcoma tumor showed maximum accumulation in the tumor to the
      extent of approximately 0.52 % ID/g at 30 min post-injection (pi). The major
      clearance of the complex was through the hepatobiliary route. The complex showed
      tumor/muscle ratio of 1.75 at 30 min pi, which significantly increased to 17 at
      180 min pi. However, the tumor/blood ratio was below one throughout the period of
      study, which could be due to slow clearance of the complex from blood.

PMID- 16949292
TI  - Insecticidal lead identification by screening benzopyrano[4,3-c] pyrazol-3(2H)
      ones library constructed from multiple-parallel synthesis under microwave
      irradiation.
AB  - A rapid library-generation via liquid-phase multiple-parallel synthesis of 2
      (substituted)benzyl-1-benzopyrano[4,3-c]pyrazol-3(2H)-ones, bearing two points of
      diversity, under microwave irradiation was successfully performed using
      chromenone-3-carboxylic acids as starting materials. Compared to an identical
      library generated by conventional parallel synthesis, microwave-assisted parallel
      synthesis dramatically decreased reaction times from an average of 16h to 13min,
      and the yields of products and intermediates were improved in most cases. A
      bioassay indicated that the compounds of the library exhibited excellent
      insecticidal activity against T. cinnabarinus at the dosage of 250mgL(-1), and
      some compounds still exhibited insecticidal activity when the dosage was reduced
      to 50mgL(-1). This shows that 2-(substituted) benzyl-1-benzopyrano[4,3-c]pyrazol
      3(2H)-ones might be used as lead structures for further optimization. To our
      knowledge, this is the first report about the application of solution-phase
      multiple-parallel synthesis under microwave irradiation to construct libraries of
      benzopyrano-[4,3-c]pyrazol-3(2H)-ones with insecticidal activity. The coupling of
      microwave technology with liquid-phase parallel synthesis constitutes a novel and
      particularly attractive avenue for the rapid generation of structurally diverse
      libraries for lead discovery.

PMID- 16949293
TI  - Anti-cancer activities of 5-acyl-6-[2-hydroxy/benzyloxy-3-(amino)-propylamino]
      1,3-dialkyl-1H-pyrimidin-2,4-diones.
AB  - All the nine 1,3-dialkylated-pyrimidin-2,4-diones investigated are active against
      all the 59 human tumor cell lines. Compounds 2, 3, 4, and 6 show significant anti
      cancer activities at some specific cell lines while compounds 7 and 9 exhibit
      anti-cancer activities against more number of cell lines. The structure-activity
      relationship studies indicate that the presence of piperidine/pyrrolidine at the
      end of C-6 chain, benzoyl group at C-5, and benzyl groups at N-1, N-3 of the
      pyrimidine ring increases the anti-cancer activities of these molecules.

PMID- 16949294
TI  - Hydrazones of 2-aryl-quinoline-4-carboxylic acid hydrazides: synthesis and
      preliminary evaluation as antimicrobial agents.
AB  - A new series of 2-arylquinoline-4-carboxylic acid hydrazide-hydrazones was
      synthesized using an appropriate synthetic route. All the target compounds were
      evaluated for their in vitro antimicrobial activity against Staphylococcus aureus
      as an example for Gram-positive bacteria, Escherichia coli as an example for Gram
      negative bacteria, and Candida albicans as a representative of fungi. The minimum
      inhibitory concentration (MIC) was determined for test compounds as well as for
      reference standards. Among the compounds tested, compounds having nitro
      substituents at the arylidene moiety showed the most potent antifungal as well as
      antibacterial activities against E. coli. Compound 23 displayed an antifungal
      activity comparable to that of nystatin. However, none of the compounds
      demonstrated any antibacterial activity against S. aureus. Hydrophobicity of the
      target compounds correlated weakly with their antibacterial and antifungal
      activities. The most potent compounds namely, 7, 18, 19, 22, and 23 were assessed
      for hemolytic toxicity and found to be non-hemolytic up to a concentration of
      100mug/mL. In addition, the most potent compound (23) was evaluated for in vitro
      cytotoxic activity against various cancer cell lines. This compound was found to
      display no cytotoxic activity but rather it induces the proliferation rate of Hep
      G2 cells.

PMID- 16949295
TI  - On-site gamma-ray spectroscopic measurements of fission gas release in irradiated
      nuclear fuel.
AB  - An experimental, non-destructive in-pool, method for measuring fission gas
      release (FGR) in irradiated nuclear fuel has been developed. Using the method, a
      significant number of experiments have been performed in-pool at several nuclear
      power plants of the BWR type. The method utilises the 514 keV gamma-radiation
      from the gaseous fission product (85)Kr captured in the fuel rod plenum volume. A
      submergible measuring device (LOKET) consisting of an HPGe-detector and a
      collimator system was utilised allowing for single rod measurements on virtually
      all types of BWR fuel. A FGR database covering a wide range of burn-ups (up to
      average rod burn-up well above 60 MWd/kgU), irradiation history, fuel rod
      position in cross section and fuel designs has been compiled and used for
      computer code benchmarking, fuel performance analysis and feedback to reactor
      operators. Measurements clearly indicate the low FGR in more modern fuel designs
      in comparison to older fuel types.

PMID- 16949297
TI  - Therapeutic management of metastatic brain tumors.
AB  - Whole brain radiation therapy (WBRT) for patients with brain metastases provides
      increased local control, locoregional control, and median survival over
      supportive care or steroids alone. In addition, effective palliative relief is
      realized in the majority of patients. Despite this, median survival with WBRT
      alone remains fixed at a relatively unfortunate 4-6 months as demonstrated in
      prospective randomized controlled trials. Key issues in the therapeutic
      management of brain metastases include techniques to optimize the multimodal
      application of WBRT in conjunction with surgery, radiosurgery, chemotherapy, and
      radiosensitizers. Efforts to incorporate these approaches to improve survival are
      currently under active investigation.

PMID- 16949298
TI  - Chemotherapy in neoplastic meningitis.
AB  - Neoplastic meningitis (NM) is the result of the diffuse or multifocal
      localization of cancer cells in the cerebral spinal fluid (CSF). NM is more often
      a late complication of solid tumor or lymphoproliferative malignancies. At
      present, the goal of therapeutic strategies is palliative and the evaluation of
      high or low risk is important in identifying which patients could benefit from
      aggressive treatments such as radiation therapy and chemotherapy. Given that NM
      is a cancer complication that can spread throughout the entire subarachnoid
      space, chemotherapy, whether intrathecal or systemic, is currently considered the
      best treatment option, but optimal treatment is still controversial. This review
      summarizes intrathecal and systemic chemotherapeutic options in the treatment of
      NM and the related toxicities.

PMID- 16949299
TI  - Specific H+/K(+)-ATPase inhibitors decreased contractile responses of isolated
      rat vas deferens.
AB  - The effect of H(+)/K(+)-ATPase inhibitors on rat vas deferens contractility was
      investigated in vitro. Omeprazole (100-300microM), lansoprazole (100-300microM)
      and SCH 28080 (10-100microM) (2-methyl-8-(phenylmethoxy)-imidazo[1,2-a]pyridine-3
      acetonitrile) decreased contractile responses of vas deferens to electrical field
      stimulation, high K(+) (80mM) and phenylephrine in a reversible, reproducible and
      concentration-dependent manner. The inhibitory potency of lansoprazole on vas
      deferens contractility was increased in relatively acidic solution (pH 6.9),
      suggesting that the site of action may be related to H(+)/K(+)-ATPase. However,
      lansoprazole-induced inhibition on contractility was unaltered in K(+) free
      solution, indicating that the mechanism of action is independent from H(+)/K(+)
      ATPase. Reversible nature of omeprazole and lansoprazole-induced inhibition on
      contractility also suggests that the effects are not due to inhibition of
      H(+)/K(+)-ATPase, since both compounds are irreversible inhibitors of the enzyme.
      Presence of ouabain (5microM) did not decrease lansoprazole-induced inhibition on
      contractility but potentiated the inhibitory effect of lansoprazole, suggesting
      that lansoprazole-induced inhibition is not mediated by the inhibition of
      Na(+)/K(+)-ATPase. Calcium-induced contractions in high K(+)-Ca(2+) free medium
      were completely antagonized by lansoprazole, implying that lansoprazole inhibits
      Ca(2+) entry through voltage-gated channels. In conclusion, three H(+)/K(+)
      ATPase inhibitors decreased contractile responses of rat vas deferens to various
      stimulants in vitro. They may act on a common mechanism, which plays a crucial
      role in regulating rat vas deferens contractility and this mechanism is probably
      involved in the regulation of intracellular Ca(2+).

PMID- 16949300
TI  - Recombinant production of a VL single domain antibody in Escherichia coli and
      analysis of its interaction with peptostreptococcal protein L.
AB  - A kappa-light chain from a Fab expression system was truncated by the insertion
      of a stop codon in the gene sequence to produce a variable light (VL) single
      domain antibody (dAb). Here, we describe the expression of dAb in the periplasm
      of Escherichia coli through fermentation in a defined media. Immunoglobulin
      binding domains from peptostreptococcal protein L (PpL) have been shown to bind
      specifically to kappa-light chains. We have produced recombinant PpL, at high
      yield, and this was used to custom-produce PpL-Sepharose affinity columns. Here,
      we show that the affinity purification of VL dAb by this method is simple and
      efficient with no apparent loss in protein at any stage. The truncated dAb
      protein product was confirmed by electrospray mass spectrometry and N-terminal
      sequencing. When analyzed by SDS-PAGE it was shown to be over 95% pure and
      produced at yields of 35-65 mg/L of culture medium. The dAb protein produced was
      shown by NMR and CD to be a folded beta-sheet domain. This domain is bound by PpL
      with a Kd of approximately 50 nM as determined by stopped-flow fluorimetry.

PMID- 16949301
TI  - High-level constitutive expression in Pichia pastoris and one-step purification
      of phospholipase D from cowpea (Vigna unguiculata L. Walp).
AB  - Phospholipase D (PLD) is one of the main enzymes involved in signal transduction,
      vesicle trafficking and membrane metabolism processes. Here we describe the
      heterologous high-yield expression in the yeast Pichia pastoris, one-step
      purification and characterization of catalytically active PLDalpha from cowpea
      (Vigna unguiculata L. Walp). Immunoblotting experiments showed that recombinant
      PLDalpha is recognized by a polyclonal antibody raised against native soybean
      PLDalpha. A single calcium-dependent octyl-Sepharose chromatography step was used
      to obtain a highly purified recombinant PLDalpha, as attested by gel
      electrophoresis, N-terminal amino acid sequence and mass spectrometry data. From
      1L of yeast culture medium, about 8 mg of pure recombinant PLDalpha was obtained
      and the specific activity measured on phosphatidylcholine was 27 micromol/min/mg.
      Contrary to what was observed previously with Vigna unguiculata PLDalpha
      expressed in insect cells, no proteolytic degradation of the N-terminal calcium
      dependent C2 lipid binding domain was observed here. This functional recombinant
      PLDalpha should provide a valuable tool for performing detailed studies on the
      molecular characterization of enzymes as well as structural studies.

PMID- 16949302
TI  - A fully automatic 3D reconstruction method using simulated annealing enables
      accurate posterioric angular assignment of protein projections.
AB  - Single-particle analysis is a structure determining method using electron
      microscopic (EM) images, which does not require protein crystal. In this method,
      projections are picked up and used to reconstruct a three-dimensional (3D)
      structure. When the conical tilting method is not available, the particle images
      are usually classified and averaged to improve the signal-to-noise ratio. The
      Euler angles of these average images must be posteriorically assigned to create a
      primary 3D model. We developed a new, fully automatic unsupervised Euler angle
      assignment method, which does not require an initial 3D reference and which is
      applicable to asymmetric molecules. In this method, the Euler angle of each
      average image is initially set randomly and then automatically corrected in
      relation to those of the other averages by iterated optimizations using the
      Simulated Annealing (SA) algorithm. At each iteration, the 3D structure is
      reconstructed based on the current Euler angles and reprojected back in the
      average-input directions. A modified cross-correlation between each reprojection
      and its corresponding original average is then calculated. The correlations are
      summed as a total 3D echo-correlation score to evaluate the Euler angles at this
      iteration. Then, one of the projections is selected, its Euler angle is changed
      randomly, and the score is also calculated. Based on the score change, judgment
      of whether to accept or reject the new angle is made using the SA algorithm,
      which is introduced to overcome the local minimums. After a certain number of
      iterations of this process, the angles of all averages converge so as to create a
      reliable primary 3D model. This echo-correlated 3D reconstruction with simulated
      annealing also has potential for wide application to general 3D reconstruction
      from various types of 2D images.

PMID- 16949303
TI  - Inhibition and generation of saccades: rapid event-related fMRI of prosaccades,
      antisaccades, and nogo trials.
AB  - Flexible, adaptive behavior often requires the inhibition of automatic responses
      in favor of voluntary response generation. The antisaccade task requires active
      inhibition of the automatic saccade to a peripheral stimulus followed by
      generation of a voluntary antisaccade to the opposite location. Previous studies
      demonstrated greater functional magnetic resonance imaging (fMRI) activation for
      antisaccades than prosaccades in cortical saccade areas but did not distinguish
      the relative contributions of saccadic inhibition and generation. To address this
      question, we compared prosaccades, antisaccades, and nogo trials in a rapid event
      related fMRI experiment with ten human subjects (6 female, 4 male). Trials were
      compound, containing a colored fixation point to cue trial type, followed by a
      200-ms gap and then peripheral stimulus presentation and response. Required
      responses for prosaccade, antisaccade, and nogo trials, respectively, were to
      generate a saccade to the stimulus, look away from it, and inhibit the automatic
      saccade while maintaining central fixation. Frontal and supplementary eye fields,
      anterior cingulate cortex, intraparietal sulcus, and precuneus, exhibited
      surprisingly similar activation patterns for prosaccade and nogo responses,
      suggesting that BOLD signal in cortical saccade regions might predominantly
      reflect visual detection and attention processes rather than saccade generation
      or inhibition. These regions displayed greater activation for antisaccade
      responses versus prosaccade or nogo responses, possibly due to visuospatial
      remapping or increased attention levels in the antisaccade task. In right
      superior frontal sulcus, right supramarginal gyrus, and posterior cingulate
      sulcus, activation was greater for nogo compared to prosaccade responses,
      suggesting a role in active saccadic inhibition.

PMID- 16949304
TI  - The human inferior parietal cortex: cytoarchitectonic parcellation and
      interindividual variability.
AB  - The inferior parietal cortex (IPC) integrates information from different sensory
      modalities and plays an important role in a variety of higher cognitive
      functions. Brodmann (Brodmann, K., 1909. Vergleichende Lokalisationslehre der
      Grosshirnrinde. Barth, Leipzig) proposed a cytoarchitectonic subdivision of the
      IPC into only two cortical areas, a rostral (BA 40) and a caudal (BA 39) area.
      Although his scheme was repeatedly challenged by other observers, it is still
      used for the anatomical localization of functional imaging data. The apparent
      differences between all these cyto- and myeloarchitectonic maps may be caused
      partly by the observer-dependent procedure of defining cytoarchitectonic borders
      by pure visual inspection of histological sections and partly by the
      interindividual variability of cytoarchitecture. The present observations and the
      resulting cortical map of the IPC are based on quantitative, observer-independent
      definitions of cytoarchitectonic borders and take into account each area's
      topographical variability across brains. Ten human postmortem brains were scanned
      using an MRI 3-D FLASH sequence prior to histological processing. After embedding
      in paraffin, serial sections through whole brains were prepared, and the sections
      were stained for cell bodies. Following high-resolution digitization of sections
      containing the IPC, we defined the cytoarchitecture and borders of each cortical
      area of this brain region using a multivariate statistical analysis of laminar
      cell density profiles. In contrast to previous observations, we found seven
      cytoarchitectonic areas in the IPC: five in the rostral (covering the region of
      BA 40) and two in the caudal part (covering the region of BA 39). We observed
      considerable interindividual variability in the topography of each area. A
      consistent correspondence between macroanatomical landmarks and cytoarchitectonic
      borders was not found. This new cytoarchitectonic map of the human IPC
      demonstrates regional differences in the cortical microstructure that is
      suggestive of functional differentiation. Furthermore, the map is registered in
      three dimensions and thereby provides a robust anatomical base for interpreting
      functional imaging studies.

PMID- 16949305
TI  - Assessing nigrostriatal dysfunctions by pharmacological MRI in parkinsonian
      rhesus macaques.
AB  - New imaging techniques are needed to longitudinally monitor the development,
      progression and treatment of Parkinson's disease. The present study was designed
      to test whether the blood oxygenation level-dependent (BOLD) response to
      dopaminergic stimulation as measured by pharmacological MRI (phMRI) correlated to
      specific histological and behavioral features of the parkinsonian state. Nine
      adult rhesus monkeys were rendered hemiparkinsonian by intracarotid
      administration of MPTP. Three months after MPTP treatment, the trained, MRI
      adapted awake animals were scanned with a phMRI technique while being
      administered a presynaptic (D-amphetamine) or postsynaptic (apomorphine) dopamine
      stimulating agents. The primary findings were (1) the putamen and substantia
      nigra (SN) but not the caudate nucleus displayed significant BOLD responses to
      these dopaminergic drugs; (2) a significant relationship was found between
      amphetamine-evoked activation and the number of surviving dopamine neurons in the
      SN, which was also correlated with bradykinesia; and (3) inverse relationships
      were seen in response to apomorphine and amphetamine stimulation between the MPTP
      lesioned and unlesioned putamen and SN. The results suggest that phMRI may prove
      useful for longitudinally monitoring the progression and treatment of PD.

PMID- 16949306
TI  - Automatic attention orienting by social and symbolic cues activates different
      neural networks: an fMRI study.
AB  - Visual attention can be automatically re-oriented by another person's non
      predictive gaze as well as by symbolic arrow cues. We investigated whether the
      shifts of attention triggered by biologically relevant gaze cues and biologically
      non-relevant arrow cues rely on the same neural systems by comparing the effects
      of gaze-cued and arrow-cued orienting on blood oxygenation level-dependent (BOLD)
      signal in humans. Participants detected laterally presented reaction signals
      preceded by centrally presented non-predictive gaze and arrow cues. Directional
      gaze cues and arrow cues were presented in separate blocks. Furthermore, two
      separate control blocks were run in which non-directional cues (straight gaze or
      segment of a line) were used. The BOLD signals during the control blocks were
      subtracted from those during the respective blocks with directional cues.
      Behavioral data showed that, for both cue types, reaction times were shorter on
      congruent than incongruent trials. Imaging data revealed three foci of activation
      for gaze-cued orienting: in the left inferior occipital gyrus and right medial
      and inferior occipital gyri. For arrow-cued orienting, a much more extensive
      network was activated. There were large postcentral activations bilaterally
      including areas in the medial/inferior occipital gyri and medial temporal gyri
      and in the left intraparietal area. Interestingly, arrow cuing also activated the
      right frontal eye field and supplementary eye field. The results suggest that
      attention orienting by gaze cues and attention orienting by arrow cues are not
      supported by the same cortical network and that attention orienting by symbolic
      arrow cues relies on mechanisms associated with voluntary shifts of attention.

PMID- 16949307
TI  - Naming taxa from cladograms: a cautionary tale.
AB  - The recent publication of a new hypothesis of cladistic relationships among
      American frogs referred to the genus Rana, accompanied by a new taxonomy and a
      new nomenclature of this group [Hillis D.M., Wilcox, T.P., 2005. Phylogeny of the
      New World true frogs (Rana). Molecular Phylogenetics and Evolution 34, 299-314],
      draws attention to the problems posed by the use of a "double nomenclature",
      following both the rules of the International Code of Zoological Nomenclature
      (designated here as "onomatophore-based nomenclature") and the rules of the draft
      Phylocode (designated here as "definition-based nomenclature"). These two
      nomenclatural systems, which rely upon widely different theoretical bases, are
      incompatible, and the latter cannot be viewed as a "modification" of the former.
      Accordingly, scientific names (nomina) following both systems should be clearly
      distinguished in scientific publications. Onomatophore-based nomina should
      continue to be written as they have been for about 250 years, whereas definition
      based nomina should be written in a specific way, e.g., Lithobates. The combined
      use of both nomenclatural systems for the same taxonomy in the same paper
      requires good knowledge and careful respect of the rules of the Code regarding
      availability, allocation and validity of nomina. As shown by this example, not
      doing so may result in various problems, in particular in publishing nomina nuda
      or in using nomenclatural ranks invalid under the current Code. Attention is
      drawn to the fact that new nomina published without diagnostic characters are not
      available under the Code, and that the latter currently forbids the use of more
      than two ranks (subgenus and "aggregate of species") between the ranks genus and
      species.

PMID- 16949308
TI  - Re-examination and phylogeny of the genus Chondrostoma based on mitochondrial and
      nuclear data and the definition of 5 new genera.
AB  - Previous molecular phylogenetic studies of the genus Chondrostoma (Cyprinidae:
      Leuciscinae) were unable to resolve the relationship among its major species
      groups. In this paper we present a phylogeny for this genus, based on five
      mitochondrial genes and the nuclear gene beta-actin, comprising a total of 4068
      bp. Bayesian inference using all gene fragments yielded a fully resolved
      phylogeny, compatible with topologies obtained from individual fragments using
      maximum parsimony and minimum evolution. Mapping of morphological characters
      critical to the rasping feeding mode of most Chondrostoma species indicates that
      they evolved several times, and questions the use of these characters in the
      traditional definition of the genus. Our findings led us to the definition of the
      following new genera: Achondrostoma, Iberochondrostoma, Pseudochondrostoma,
      Protochondrostoma and Parachondrostoma. Our data contradict the hypothesis of a
      rapid radiation during Lago Mare phase, suggested by previous studies.

PMID- 16949309
TI  - Lineage divergence of a freshwater snail clade associated with post-Tethys marine
      basin development.
AB  - The complex evolutionary history of the Eurasian gastropod lineage Theodoxus
      reflects the evolution of marine basins following the breakup of the Tethys Sea.
      Today, this clade inhabits the lakes, rivers, streams, and estuaries of Europe,
      southwestern Asia, and North Africa. Here we present the first phylogenetic
      hypothesis for this clade. Based upon extensive geographic and taxonomic
      sampling, portions of the mitochondrial genes for cytochrome c oxidase subunit I
      and 16S rRNA were sequenced and analysed using maximum likelihood and maximum
      parsimony methods. Results from bootstrap analyses, Bayesian analysis, and
      sensitivity analyses lend support to six deep phylogenetic subdivisions within
      Theodoxus. These major clades are geographically associated with the major post
      Tethyan marine basins. Estimates of divergence times using a penalized likelihood
      approach indicate that divergence of these major lineages occurred during the
      Miocene, simultaneous with the breakup of the Mediterranean and Paratethys Seas.
      The resulting major subclades later diversified during the Pliocene, primarily
      within geographic regions associated with the eastern and western Mediterranean
      Sea, the Pannonian Basin, and the Black Sea, thus producing the extant species
      assemblages. Finally, these phylogenetic results imply that much of the current
      taxonomy is flawed, therefore we offer recommendations for revising the
      classification of Theodoxus species based on phylogenetic systematics.

PMID- 16949310
TI  - Incongruent plastid and nuclear DNA phylogenies reveal ancient intergeneric
      hybridization in Pilosella hawkweeds (Hieracium, Cichorieae, Asteraceae).
AB  - Phylogenetic relationships for Hieracium subgen. Pilosella were inferred from
      chloroplast (trnT-trnL, matK) and nuclear (ITS) sequence data. Chloroplast
      markers revealed the existence of two divergent haplotype groups within the
      subgenus that did not correspond to presumed relationships. Furthermore,
      chloroplast haplotypes of the genera Hispidella and Andryala nested each within
      one of these groups. In contrast, ITS data were generally in accord with
      morphology and other evidence and were therefore assumed to reflect the true
      phylogeny. They revealed a sister relationship between Pilosella and Hispidella
      and a joint clade of Hieracium subgenera Hieracium and Chionoracium (Stenotheca)
      while genus Andryala represented a third major lineage of the final ingroup
      cluster. Detailed analysis of trnT-trnL character state evolution along the ITS
      tree suggested two intergeneric hybridization events between ancestral lineages
      that resulted in cytoplasmic transfer (from Hieracium/Chionoracium to Pilosella,
      and from the introgressed Pilosella lineage to Andryala). These chloroplast
      capture events, the first of which involved a now extinct haplotype, are the most
      likely explanation for the observed incongruencies between plastid and nuclear
      DNA markers.

PMID- 16949311
TI  - A phylogeny for the Cisticolidae (Aves: Passeriformes) based on nuclear and
      mitochondrial DNA sequence data, and a re-interpretation of an unique nest
      building specialization.
AB  - Based on some general similarities in feeding adaptations, a large number of Old
      World passerine birds were in the past lumped in one broad family, the Sylviidae.
      Recent molecular studies, starting with the DNA-DNA hybridization work by Sibley
      et al. [Sibley, C.G., Ahlquist, J.E., 1990. Phylogeny and Classification of
      Birds: A Study in Molecular Evolution, Yale University Press, New Haven, CT],
      have revealed that this group is in fact a paraphyletic assemblage, mainly in the
      superfamily Sylvioidea, and within this assemblage a distinct group (the
      Cisticolidae) can be identified around the genus Cisticola. In this study we try
      to define natural lineages within it, based on DNA sequence data from 35 ingroup
      taxa representing 12 putative genera. Both nuclear myoglobin intron II (630 bp in
      our study) and mitochondrial ND2 (1041 bp) genes were sequenced, and 1671 bp were
      aligned and subjected to parsimony, maximum likelihood and Bayesian analyses. The
      results strongly support the monophyly of a cisticolid clade, with the Malagasy
      warblers Neomixis constituting the deepest branch within the clade. Three major
      clades receive statistical support, but not all relationships between and within
      these are well resolved. All species of the genus Bathmocercus belong to the
      Cisticolidae but in two different clades. The tailorbirds appear also
      polyphyletic with most species of the genus Orthotomus (but O. cucullatus falling
      in the outgroup) and the African metopias being in two different clades. Also the
      genus Apalis is polyphyletic, but all other included genera seem to be confirmed
      as natural units. Based on these findings we resurrect the genera Scepomycter and
      Artisornis. Calamonastes is confirmed to be in the Cisticolidae and grouped with
      Camaroptera. Main basic nest types do not follow the phylogenetic branching, and
      notably the peculiar "tailorbird" technique of stitching leaves together around
      the nest is found in different parts of the phylogeny. The basic types of nests
      seem to be found in particular environments, and the sewing may therefore have
      evolved in some ancestor of the Cisticolidae and was later lost or modified in
      some genera or species following the spread of drier habitats from the mid
      Miocene.

PMID- 16949312
TI  - Effects of pleiotrophin, a heparin-binding growth factor, on human primary and
      immortalized chondrocytes.
AB  - OBJECTIVE: Pleiotrophin (PTN) is a secreted heparin-binding peptide expressed in
      mesodermal and neuroectodermal cells during development, but rarely in adult
      tissues. In fetal and juvenile, but not in mature cartilage, PTN is abundant.
      Furthermore, PTN is re-expressed in chondrocytes in early stages of
      osteoarthritis (OA). Since little is known about the functions of PTN in
      cartilage, we investigated the occurrence of PTN receptors in human articular
      cartilage in situ and PTN effects on human primary and immortalized chondrocytes
      in vitro. METHODS: Receptor expression and regulation was monitored by
      quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and
      immunohistochemistry. PTN effects and signal transduction were studied by
      electrophoretic mobility shift, Boyden chamber cell migration and proliferation
      assays, effects on gene expression by real time RT-PCR and that on nitric oxide
      (NO) by the Griess reaction. RESULTS: Of the putative PTN signaling receptors,
      immortalized and primary chondrocytes (pc) expressed the anaplastic lymphoma
      kinase (ALK), less the receptor-type protein tyrosine phosphatase zeta/beta
      (PTPzeta). ALK expression was upregulated upon ligand exposure. PTN stimulation
      activated the AP-1 (activator protein-1) transcription factor and altered gene
      expression. Prolonged stimulation induced PTN mRNA expression slightly, reduced
      vascular endothelial growth factor (VEGF) mRNA as well as NO production. Whereas
      mRNA expression of matrix metalloproteinases (MMPs) MMP-1 and MMP-13 was reduced,
      their inhibitors TIMP-1 and TIMP-2 were induced. Furthermore, PTN stimulated
      chondrocyte migration and proliferation. CONCLUSIONS: These results show that PTN
      is an autocrine growth factor in cartilage. We suggest that PTN may be involved
      in the clustering and proliferation of chondrocytes observed in the early stages
      of OA.

PMID- 16949313
TI  - Clinical evaluation of T2 values of patellar cartilage in patients with
      osteoarthritis.
AB  - OBJECTIVE: The transverse relaxation time constant, T2, of articular cartilage
      has been proposed as a biomarker for osteoarthritis (OA). Previous studies have
      not clearly defined the relationship between cartilage T2 values and clinical
      methods of grading OA or known factors associated with OA. This study compared T2
      values of patellar cartilage grouped by radiographic stage of patello-femoral OA
      and by body mass index (BMI). METHODS: T2 values of patellar cartilage were
      calculated for 113 subjects using images acquired on a 1.5 T clinical scanner.
      Radiographs of the patello-femoral joint were graded for OA grading using the
      Kellgren-Lawrence scale. RESULTS: No differences of T2 values were found across
      the stages of OA (P = 0.25), but the factor of BMI did have a significant effect
      (P < 0.0001) on T2 value. CONCLUSIONS: The results indicate the T2 values are not
      sensitive to changes in radiographic stages of OA. In addition, differences of T2
      values with BMI signify structural changes occurring within the patello-femoral
      joint and that BMI may be considered a factor for a potential increase of T2
      values. Future studies comparing different OA grading methods with T2 mapping may
      highlight the sensitivity of T2 mapping in a clinical setting.

PMID- 16949314
TI  - HC-gp39 contributes to chondrocyte differentiation by inducing SOX9 and type II
      collagen expressions.
AB  - OBJECTIVE: The transcription factor SOX9 has been shown to be linked to
      chondrocyte differentiation and induction of type II collagen synthesis. Since
      the chitinase-like protein, human cartilage glycoprotein 39 (HC-gp39), can be
      expressed by articular chondrocytes and has been shown to enhance chondrocyte
      mitogenesis through MAP kinase and PI3 kinase-mediated signalling, we
      hypothesized that it may also promote synthesis of cartilage matrix components
      through induction of SOX9, utilizing similar signalling pathways. METHODS:
      Primary chondrocytes from neonatal mouse rib cartilage were exposed to purified
      HC-gp39. The response of the cells was evaluated in terms of SOX9 induction and
      synthesis of type II collagen. Signalling pathways activated following HC-gp9
      exposure were analyzed by Western blotting of cell lysates with phosphorylation
      specific antibodies as well as by using selective inhibitors. RESULTS: HC-gp39
      induced both SOX9 and type II collagen synthesis. Similar results were observed
      for IGF-1. This process required signalling through both MAP kinase and PI3
      kinase pathways resulting in rapid phosphorylation of ERK1/2 and AKT,
      respectively. Neither HC-gp39 nor IGF-1 induced activation of SAPK/JNK.
      CONCLUSIONS: The effects of HC-gp39 on chondrocyte function suggest that this
      molecule may promote the maintenance or expression of a chondrocytic phenotype.
      Its expression in injured or degenerate cartilage could be related to the initial
      repair-response and increased matrix synthesis observed in osteoarthritic
      cartilage.

PMID- 16949315
TI  - Nucleotide binding oligomerization domain 2 deficiency leads to dysregulated TLR2
      signaling and induction of antigen-specific colitis.
AB  - In this study, we determined conditions leading to the development of colitis in
      mice with nucleotide binding oligomerization domain 2 (NOD2) deficiency, a
      susceptibility factor in Crohn's disease. We found that NOD2-deficient antigen
      presenting cells (APCs) produced increased amounts of interleukin (IL)-12 in the
      presence of ovalbumin (OVA) peptide and peptidoglycan or recombinant E. coli that
      express OVA peptide (ECOVA). Furthermore, these APCs elicited heightened
      interferon-gamma (IFN-gamma) responses from cocultured OVA-specific CD4+ T cells.
      We then demonstrated that NOD2-deficient mice adoptively transferred OVA-specific
      CD4+ T cells and that administered intrarectal ECOVA developed colitis associated
      with the expansion of OVA-specific CD4+ T cells producing IFN-gamma. Importantly,
      this colitis was highly dependent on Toll-like receptor 2 (TLR2) function since
      it was suppressed in NOD2 and TLR2 double-deficient mice. Thus, NOD2-deficient
      mice become susceptible to colitis as a result of increased TLR2 responses when
      they have the capacity to respond to an antigen expressed by mucosal bacteria.

PMID- 16949316
TI  - Granulocyte-macrophage colony-stimulating factor regulates effector
      differentiation of invariant natural killer T cells during thymic ontogeny.
AB  - Invariant natural killer T (iNKT) cell-derived cytokines have important functions
      in inflammation, host defense, and immunoregulation. Yet, when and how iNKT cells
      undergo effector differentiation, which endows them with the capacity to rapidly
      secrete cytokines upon activation, remains unknown. We discovered that
      granulocyte-macrophage colony-stimulating factor (Csf-2)-deficient mice developed
      iNKT cells that failed to respond to the model antigen alpha-galactosylceramide
      because of an intrinsic defect in the fusion of secretory vesicles with the
      plasma membrane. Exogenous Csf-2 corrected the functional defect only when
      supplied during the development of thymic, but not mature, splenic Csf-2
      deficient iNKT cells. Thus, we ascribe a unique function to Csf-2, which
      regulates iNKT cell effector differentiation during development by a mechanism
      that renders them competent for cytokine secretion.

PMID- 16949317
TI  - Evaluating the efficacy of serum haptoglobin concentration as an indicator of
      respiratory-tract disease in dairy calves.
AB  - The serum concentration of haptoglobin (S-Hp) was measured in 833 group-housed
      dairy calves from nine herds in south-west Sweden once at 24-56 days of age to
      evaluate the potential of S-Hp as an indicator of clinical respiratory-tract
      disease (CRD). Presence of disease (treated and non-treated) was assessed
      clinically by farmers and by a project veterinarian visiting the farms every
      third week. The median S-Hp of healthy calves was 0.06g/L (80% central range:
      0.04-0.23), of calves with diarrhoea within the 10 days before sampling 0.07g/L
      (80% central range: 0.04-0.63), and of calves with CRD within the 14 days before
      sampling 0.09g/L (80% central range: 0.04-0.69). Eight different cut-off values
      were used to define a positive S-Hp analysis result: >0.05, >0.06, >0.07, >0.08,
      >0.09, >0.10, >0.15 and >0.20g/L. A rectal temperature >39.5 degrees C was
      denoted as fever. A positive result of five different diagnostic tests for CRD
      was defined as: (1) a positive S-Hp with fever absent, (2) a positive S-Hp with
      fever present, (3) either a positive S-Hp or fever, (4) both a positive S-Hp and
      fever, and (5) fever (regardless of S-Hp). The sensitivity (Se) and specificity
      (Sp) of each test were calculated from regression coefficients of generalized
      linear mixed models of the binary test results, applying a logit link. Apart from
      CRD status (within the 14 days before sampling; no or yes), the models included
      sex (bull or heifer), and for the test based on S-Hp alone, also rectal
      temperature (fever, no or yes). Confidence intervals (CI) of Se and Sp were
      estimated by simulation. Based on Se, Sp, and areas under Receiver Operating
      Characteristics curves, test 3 was considered the best. At optimal performance,
      giving equal importance to type I and II errors, i.e. at a S-Hp cut-off of
      0.15g/L in heifer calves, Se was 0.64 (95% CI 0.50-0.77) and Sp 0.71 (95% CI 0.60
      0.80), and at a S-Hp cut-off of 0.08g/L in bulls, Se was 0.52 (95% CI 0.40-0.64)
      and Sp 0.80 (95% CI 0.74-0.85). The other tests were judged as unsatisfactory
      indicators of CRD. In heifers, the proportion of CRD-positive calves in the herd
      was strongly associated with the proportion of test positives (S-Hp or fever; S
      HP and fever), suggesting potential as a herd-level indicator.

PMID- 16949318
TI  - The effect of pre-calving environment on the development of digital dermatitis in
      first lactation heifers.
AB  - Digital dermatitis is commonly reported to be most severe in first lactation
      heifers. It has been suggested that this initial infection is followed by the
      development of a limited immunity to the organisms which cause digital
      dermatitis. If this is the case then exposure to digital dermatitis prior to
      calving should reduce its severity after calving. A study was undertaken to
      examine whether such exposure significantly affected the development of digital
      dermatitis post-partum. Twelve weeks prior to calving, 60 Holstein heifers were
      blocked on the basis of their antibody titre to Borrelia burgdorferi and randomly
      allocated to one of three pre-calving environments: clean straw, used straw or
      cubicles. There was no significant effect of pre-calving environment on the
      development of digital dermatitis after calving indicating that "exposure" pre
      calving did not reduce the development of digital dermatitis after calving. The
      most important factors determining the development of digital dermatitis after
      calving were presence of absence of visible lesions of digital dermatitis at Week
      12 and at calving.

PMID- 16949319
TI  - Fast quantification of proton magnetic resonance spectroscopic imaging with
      artificial neural networks.
AB  - Accurate quantification of the MRSI-observed regional distribution of metabolites
      involves relatively long processing times. This is particularly true in dealing
      with large amount of data that is typically acquired in multi-center clinical
      studies. To significantly shorten the processing time, an artificial neural
      network (ANN)-based approach was explored for quantifying the phase corrected (as
      opposed to magnitude) spectra. Specifically, in these studies radial basis
      function neural network (RBFNN) was used. This method was tested on simulated and
      normal human brain data acquired at 3T. The N-acetyl aspartate (NAA)/creatine
      (Cr), choline (Cho)/Cr, glutamate+glutamine (Glx)/Cr, and myo-inositol (mI)/Cr
      ratios in normal subjects were compared with the line fitting (LF) technique and
      jMRUI-AMARES analysis, and published values. The average NAA/Cr, Cho/Cr, Glx/Cr
      and mI/Cr ratios in normal controls were found to be 1.58+/-0.13, 0.9+/-0.08,
      0.7+/-0.17 and 0.42+/-0.07, respectively. The corresponding ratios using the LF
      and jMRUI-AMARES methods were 1.6+/-0.11, 0.95+/-0.08, 0.78+/-0.18, 0.49+/-0.1
      and 1.61+/-0.15, 0.78+/-0.07, 0.61+/-0.18, 0.42+/-0.13, respectively. These
      results agree with those published in literature. Bland-Altman analysis indicated
      an excellent agreement and minimal bias between the results obtained with RBFNN
      and other methods. The computational time for the current method was 15s compared
      to approximately 10 min for the LF-based analysis.

PMID- 16949320
TI  - Performance of cryogenic probes as a function of ionic strength and sample tube
      geometry.
AB  - The pursuit for more sensitive NMR probes culminated with development of the
      cryogenic cooled NMR probe. A key factor for the sensitivity is the overall
      resistance of RF circuitry and sample. Lowering the coil temperature to
      approximately 25 K and the use of superconducting coil material has greatly
      reduced the resistance contribution of the hardware. However, the resistance of a
      salty sample remains the same and evolves as the major factor determining the
      signal-to-noise ratio. Several approaches have been proposed to reduce the
      resistance contribution of the sample. These range from encapsulating proteins in
      a water cavity formed by reverse micelles in low viscosity fluids to the optimal
      selection of low mobility, low conductivity buffer ions. Here we demonstrate that
      changing the sample diameter has a pronounced effect on the sample resistance and
      this results in dramatic improvements of the signal-to-noise ratio and shorter
      pi/2 pulses. We determined these parameters for common 5 mm NMR tubes under
      different experimental conditions and compared them to the 2, 3 and 4 mm tubes,
      in addition, 5mm Shigemi tubes were included since these are widely used. We
      demonstrate benefits and applicability of studying NMR samples with up to 4M salt
      concentrations in cryogenic probes. Under high salt conditions, best results in
      terms of short pi/2 pulses and high signal-to-noise ratios are obtained using 2
      or 3mm NMR tubes, especially when limited sample is available. The 4 mm tube is
      preferred when sample amounts are abundant at intermediate salt conditions.

PMID- 16949321
TI  - Cutaneous haemangiosarcoma of the lower eyelid in an elderly white cat.
AB  - A case of cutaneous haemangiosarcoma of the left lower eyelid in a 15-year-old
      white domestic shorthair cat is reported. A protuberant red mass occupying one
      third of the lower eyelid margin length was present. Intermittent haemorrhage
      occurred from the mass surface. Surgical biopsy had revealed a locally invasive
      tumour composed of numerous irregular blood-filled spaces lined by a single layer
      of plump endothelial cells and separated by thin fibrous septa. Mitotic activity
      was rare and the appearance was consistent with a low-grade haemangiosarcoma. The
      mass continued to enlarge and referral was sought. Due to financial constraints
      and the owner's wish for a single procedure, enucleation with an axial pattern
      flap based on the superficial temporal artery was undertaken. Histopathology of
      the excised tissue confirmed the presence of a well-differentiated
      haemangiosarcoma. Tumour-free excisional margins were confirmed, the surgical
      area healed uneventfully, and there has been no recurrence during the subsequent
      16 months.

PMID- 16949322
TI  - Effect of bacterial monoassociation on brush-border enzyme activities in ex-germ
      free piglets: comparison of commensal and pathogenic Escherichia coli strains.
AB  - This study was designed to investigate the effect of monoassociation of germ-free
      piglets with Escherichia coli strains on the development of intestinal brush
      border enzyme activities. Piglets were delivered by hysterectomy, reared for
      seven days under germ-free conditions and fed milk formula diet. One group was
      maintained germ-free, the other four groups were monoassociated on day eight with
      one of four E. coli strains: non-pathogenic O86 or O83 and G58-1, or pathogenic
      933D. The development of brush-border digestive enzyme functions in the small
      intestine was evaluated after 15 days. Germ-free controls exhibited slower
      developmental declines of lactase, gamma-glutamyltranspeptidase and alkaline
      phosphatase, and delayed increases of sucrase and glucoamylase compared to
      conventionally grown animals. Association of germ-free piglets with the non
      pathogenic E. coli strains O86 and O83 resulted in increased enterocyte
      differentiation along the length of the small intestine, accompanied by declining
      activities of lactase, gamma-glutamyltranspeptidase and alkaline phosphatase, and
      elevated activities of maturational markers such as sucrase and glucoamylase.
      Maturational changes also occurred along the villus-crypt axis, as revealed by
      histochemical localization of aminopeptidase N on the villi tips in piglets
      colonized with E. coli O83. Interestingly, colonization with the pathogenic E.
      coli strain 933D stimulated changes in the main differentiation enzyme markers
      lactase, sucrase and glucoamylase to an extent comparable with those produced by
      the non-pathogenic and probiotic E. coli strains. In conclusion, germ-free
      piglets represent a valuable tool to study the consequences of colonization of
      the immature sterile gut with defined strains of bacteria.

PMID- 16949323
TI  - Microbiology and prognosis of septic arthritis in Brazzaville.

PMID- 16949324
TI  - Adherence, persistence, concordance: do we provide optimal management to our
      patients with osteoporosis?
AB  - The last two decades have witnessed numerous advances in the treatment of chronic
      diseases, most notably those occurring in postmenopausal women. An insidious
      course and minimal symptoms often characterize chronic diseases, with the result
      that long-term adherence to prescribed treatment regimens may be difficult to
      obtain. Poor compliance has been abundantly documented, particularly in patients
      with hypercholesterolemia, hypertension, or diabetes mellitus. Many factors may
      contribute to poor compliance, including the unobtrusiveness of the symptoms,
      limited patient awareness of the potential severity of the disease and of the
      benefits expected from optimal treatment, low level of education, fear of adverse
      effects from medications, and cost of medications. The effects of these factors
      vary across countries, in particular according to the characteristics of
      healthcare systems. Several strategies are being developed to measure compliance
      and to identify reasons for non-compliance. Attention is turning to methods for
      improving compliance, some of which rest on general principles and others on the
      specific characteristics of each disease. Few data are available on compliance
      with treatments for osteoporosis, since these were introduced only within the
      last decade. In many studies, the reference standard was hormone replacement
      therapy (HRT), whose use is decreasing markedly as a result of recent data on
      adverse effects. Available studies of bisphosphonate therapy indicate a less than
      50% continuation rate after 1 year. The few comparative studies published to date
      have methodological flaws that preclude definitive conclusions. Compliance has
      been equally poor with all available bisphosphonates. Although statistically
      significant, the improvements produced by weekly dosing have been modest, about
      10%, indicating a need for further compliance-enhancing strategies. Conflicting
      results were obtained from the few studies addressing the potential of bone
      turnover marker assays for influencing compliance. Having a nurse inform patients
      about the disease and the importance of compliance with dosing recommendations
      holds promise for improving compliance.

PMID- 16949326
TI  - Unequal genetic redundancies in Arabidopsis--a neglected phenomenon?
AB  - Genetic redundancy is a common phenomenon in Arabidopsis and is thought to be
      responsible for the absence of phenotypes in the majority of single loss-of
      function mutants. In this review, we highlight an increasing number of examples
      in which redundancy between homologous genes is limited or absent despite
      functional equivalence of the respective proteins. In particular, we focus on
      cases of unequal redundancy, where the absence of a mutant phenotype in loss-of
      function mutants of one gene contrasts with a strong phenotype in mutants of its
      homolog. In the double mutants, this phenotype is strongly enhanced. Possible
      explanations for such scenarios are discussed. We propose that the study of
      unequally redundant gene pairs offers a unique opportunity to understand global
      patterns of functional genome evolution.

PMID- 16949327
TI  - Plant metabolomics: towards biological function and mechanism.
AB  - Metabolite profiling is a fast growing technology and is useful for phenotyping
      and diagnostic analyses of plants. It is also rapidly becoming a key tool in
      functional annotation of genes and in the comprehensive understanding of the
      cellular response to biological conditions. Metabolomics approaches have recently
      been used to assess the natural variance in metabolite content between individual
      plants, an approach with great potential for the improvement of the compositional
      quality of crops. Here, we assess the contribution of metabolite profiling to
      these areas.

PMID- 16949328
TI  - Medea in full self-control.
AB  - Medea, a loving but betrayed character from Greek mythology who murdered her own
      children, inspired the naming of an Arabidopsis regulatory protein involved in
      the control of endosperm development in the maturing seed. In contrast to the
      Medea of antiquity who, according to Euripides, cannot be called a model of self
      control, three recent publications demonstrate that MEDEA in plants is in command
      of its own action by autoregulation.

PMID- 16949329
TI  - Endogenous pararetroviruses: two-faced travelers in the plant genome.
AB  - Endogenous plant pararetroviruses (EPRVs) were identified as integrated
      counterparts of most members of the plant virus family Caulimoviridae and
      represent repetitive elements that are ubiquitous in the plant kingdom. They are
      often located in pericentromeric regions of plant chromosomes in the vicinity of
      retrotransposon sequences. Depending on their structure and sequence integrity,
      some EPRVs are able to replicate and to initiate viral infection. However,
      conservation of integrated sequences in plant genomes might indicate benefits for
      the host during evolution. Understanding EPRV activation and control by the host
      could have important implications for plant breeding strategies to prevent viral
      disease caused by EPRVs in newly generated cultivars.

PMID- 16949330
TI  - Computational principles of working memory in sentence comprehension.
AB  - Understanding a sentence requires a working memory of the partial products of
      comprehension, so that linguistic relations between temporally distal parts of
      the sentence can be rapidly computed. We describe an emerging theoretical
      framework for this working memory system that incorporates several independently
      motivated principles of memory: a sharply limited attentional focus, rapid
      retrieval of item (but not order) information subject to interference from
      similar items, and activation decay (forgetting over time). A computational model
      embodying these principles provides an explanation of the functional capacities
      and severe limitations of human processing, as well as accounts of reading times.
      The broad implication is that the detailed nature of cross-linguistic sentence
      processing emerges from the interaction of general principles of human memory
      with the specialized task of language comprehension.

PMID- 16949331
TI  - The empathic brain: how, when and why?
AB  - Recent imaging results suggest that individuals automatically share the emotions
      of others when exposed to their emotions. We question the assumption of the
      automaticity and propose a contextual approach, suggesting several modulatory
      factors that might influence empathic brain responses. Contextual appraisal could
      occur early in emotional cue evaluation, which then might or might not lead to an
      empathic brain response, or not until after an empathic brain response is
      automatically elicited. We propose two major roles for empathy; its
      epistemological role is to provide information about the future actions of other
      people, and important environmental properties. Its social role is to serve as
      the origin of the motivation for cooperative and prosocial behavior, as well as
      help for effective social communication.

PMID- 16949332
TI  - Imaging molecular interactions in living cells by FRET microscopy.
AB  - Forster resonance energy transfer (FRET) is applied extensively in all fields of
      biological research and technology, generally as a 'nanoruler' with a dynamic
      range corresponding to the intramolecular and intermolecular distances
      characterizing the molecular structures that regulate cellular function. The
      complex underlying network of interactions reflects elementary reactions
      operating under strict spatio-temporal control: binding, conformational
      transition, covalent modification and transport. FRET imaging provides
      information about all these molecular processes with high specificity and
      sensitivity via probes expressed by or introduced from the external medium into
      the cell, tissue or organism. Current approaches and developments in the field
      are discussed with emphasis on formalism, probes and technical implementation.

PMID- 16949333
TI  - A comparative study on the antimutagenic properties of aqueous extracts of
      Aspalathus linearis (rooibos), different Cyclopia spp. (honeybush) and Camellia
      sinensis teas.
AB  - Antimutagenic activity of aqueous extracts of the South African herbal teas,
      Aspalathus linearis (rooibos) and Cyclopia spp. (honeybush) was compared with
      that of Camellia sinensis (black, oolong and green) teas in the Salmonella
      mutagenicity assay using aflatoxin B(1) (AFB(1)) and 2-acetylaminofluorene (2
      AAF) as mutagens. The present study presents the first investigation on
      antimutagenic properties of C. subternata, C. genistoides and C. sessiliflora.
      The herbal teas demonstrated protection against both mutagens in the presence of
      metabolic activation, with the exception of "unfermented" (green/unoxidised) C.
      genistoides against 2-AAF, which either protected or enhanced mutagenesis
      depending on the concentration. Antimutagenic activity of "fermented" (oxidised)
      rooibos was significantly (P<0.05) less than that of Camellia sinensis teas
      against AFB(1), while for 2-AAF it was less (P<0.05) than that of black tea and
      similar (P>0.05) to that of oolong and green teas. Antimutagenic activity of
      unfermented C. intermedia and C. subternata exhibited a similar protection as
      fermented rooibos against AFB(1). Against 2-AAF, fermented rooibos exhibited
      similar protective properties than unfermented C. intermedia and C. sessiliflora.
      Unfermented rooibos was less effective than the C. sinensis teas and fermented
      rooibos, but had similar (P>0.05) antimutagenicity to that of fermented C.
      sessiliflora against AFB(1) and fermented C. subternata against 2-AAF. Fermented
      C. intermedia and C. genistoides exhibited the lowest protective effect against 2
      AAF, while fermented C. intermedia exhibited the lowest protection when utilising
      AFB(1) as mutagen. Aspalathin and mangiferin, major polyphenols in rooibos and
      Cyclopia spp., respectively, exhibited weak to moderate protective effects when
      compared to the major green tea catechin, (-)epigallocatechin gallate (EGCG).
      Antimutagenic activity of selected herbal tea phenolic compounds indicated that
      they contribute towards (i) observed antimutagenic activity of the aqueous
      extracts against both mutagens and (ii) enhancement of the mutagenicity of 2-AAF
      by unfermented C. genistoides. Antimutagenic activity of the South African herbal
      teas was mutagen-specific, affected by fermentation and plant material,
      presumably due to changes and variation in phenolic composition.

PMID- 16949335
TI  - Inclusion complex of 2-naphthylamine-6-sulfonate with beta-cyclodextrin:
      intramolecular charge transfer versus hydrogen bonding effects.
AB  - The photophysical characteristics of the ground and excited states of 2
      naphthylamine-6-sulfonate (2-NA-6-S) were investigated in different solvents and
      in beta-cyclodextrin (beta-CD). The spectral shifts are well correlated with
      Kamlet-Taft relationship. Multiple linear regression analysis indicated that both
      non-specific dipolar interaction and specific hydrogen bonding interactions play
      competitive roles in determining the position of the absorption maximum, while
      the dipolar interaction is the dominating parameter in determining the emission
      maximum. For the Stokes shift, both the nonspecific interaction and the hydrogen
      donation property of the solvent are participating equally. The molecular
      encapsulation of 2-NA-6-S by beta-CD in aqueous solution has been studied by
      different spectroscopic techniques. Fluorescence measurements show that the
      dielectric constant of beta-CD experienced by the included 2-NA-6-S is
      intermediate between water and methanol. The changes observed in the absorption
      and fluorescence spectra of 2-NA-6-S upon inclusion in beta-CD allowed the
      association constant to be calculated and found to be 465+/-100 and 495+/-100 M
      1, respectively. The changes observed for the chemical shifts of 2-NA-6-S and
      beta-CD 1H NMR spectra and the corresponding 1H NMR spectra of their mixture
      confirmed the formation of the inclusion complex and showed that 2-NA-6-S is
      encapsulated in beta-CD cavity in a tilted equatorial approach.

PMID- 16949334
TI  - The responses of lymphocytes from Asian and Caucasian diabetic patients and non
      diabetics to hydrogen peroxide and sodium nitrite in the Comet assay.
AB  - Numerous factors may influence the incidence of diabetes in the population. The
      production of reactive oxygen species (ROS) is elevated in diabetes patients.
      Based on the reported involvement of reactive species and nitrate/nitrite in
      diabetes, this present study has examined in the alkaline Comet assay, the effect
      of different levels of NaNO(2) in the presence of the oxygen radical generating
      agent, hydrogen peroxide (H(2)O(2)). Peripheral lymphocytes from diabetic and non
      diabetic Caucasians and Asians of both sexes were studied in vitro. Endogenous
      factors (e.g., sex, age, body mass index-BMI) and exogenous factors (lifestyle
      factors e.g., smoking and drinking habits, diet) were taken into account. A
      preliminary study in two individuals showed that DNA damage remained constant
      over a wide dose range of NaNO(2) (1-75mM), but when H(2)O(2) was added at a
      constant concentration of 50microM per dose of NaNO(2), there was an increase in
      DNA damage corresponding with the varying levels of NaNO(2) investigated. This
      was also seen with the 44 individuals (non-diabetic, n=24; type 1 diabetic, n=11;
      type 2 diabetic, n=9) investigated. NaNO(2) was capable of inducing a significant
      level of DNA damage in lymphocytes (p<0.001), but only with the addition of
      H(2)O(2). When levels of DNA damage were analysed in terms of the different
      variables there were few significant differences in damage between diabetic and
      non-diabetic subjects, or other sub-population groups, and no statistically
      significant differences in susceptibility were observed between subject
      covariates using regression techniques.

PMID- 16949336
TI  - Solvatochromic, spectroscopic and DFT studies of a novel synthesized dye: l-(4
      Dimethylaminophenyl)-2-(5H-phenanthridine-6-ylidene)-ethanone (6-KMPT).
AB  - A novel solvatochromic l-(4-dimethylaminophenyl)-2-(5H-phenanthridine-6-ylidene)
      ethanone (6-KMPT) dye was synthesized and characterized by means of NMR, IR, mass
      spectroscopies. Also, it was studied using UV-vis and fluorescence spectroscopic
      methods in a broad range of solvents. UV-vis results showed that increasing 6
      KMPT concentration dose not cause molecular aggregation in chloroform. Varying
      the temperature in the range from 25 to 55 degrees C dose not have a significant
      effect on the characteristics bands of the molecule. However, in the presence of
      surfactant SDS the UV-vis spectrum undergoes drastic alteration. This phenomenon
      is related to the removal of hydrogen atom from nitrogen atom of phenanthridine
      moiety. Fluorescence spectroscopic results showed that 6-KMPT has an appreciable
      fluorescence quantum yield. The effect of excitation wavelength, concentration of
      6-KMPT, concentration of oxygen and surfactants (SDS, C(16)TAB, CPC, Brij-35)
      were studied. Further results showed that the fluorescent behavior of 6-KMPT can
      be attributed to planarity induced by intramolecular hydrogen bonding which can
      in turn be destroyed by anionic surfactant SDS. Results showed that oxygen and
      SDS can be operate as fluorescence quencher compounds for 6-KMPT and Stern-Volmer
      plot showed a straight line. Fluorescence polarization and anisotropy of 6-KMPT
      in chloroform strongly depend on concentration. The 6-KMPT exhibits solvent
      induced spectral band shifts. By using Lippert equation, the change of dipole
      moment of 6-KMPT molecule upon excitation was estimated as 6.39 D. Furthermore,
      absorption, fluorescence emission, Stokes shift values and fluorescence quantum
      yield (Phi(F)) of 6-KMPT in different solvents of polarity were determined.
      Maximum Phi(F) value of 0.372 for 6-KMPT molecule was found in ethanol solvent
      with a Stokes shift of 2446.8 cm(-1). The results of DFT calculations showed that
      tautomer 2c (enol) energetically is more stable than tautomer 2b (keto) in gas
      phase whereas it was vice versa in CHCl(3).

PMID- 16949337
TI  - Luminescent property and catalytic activity of Ru(II) carbonyl complexes
      containing N, O donor of 2-hydroxy-1-naphthylideneimines.
AB  - The reaction of the chelating ligands (obtained by the condensation of 2-hydroxy
      1-naphthaldehyde with various primary amines) with [RuHCl(CO)(EPh(3))(2)(B)]
      (where E=P; B=PPh(3), py or pip: E=As; B=AsPh(3)) in benzene afforded new stable
      ruthenium(II) carbonyl complexes of the general formula
      [Ru(Cl)(CO)(EPh(3))(B)(L)] (L=anion of bidentate Schiff bases). The structure of
      the new complexes was investigated using elemental analyses, spectral (FT-IR, UV
      vis and (1)H NMR) and electrochemical studies and is found to be octahedral. All
      the metal complexes exhibit characteristic MLCT absorption and luminescence bands
      in the visible region. The luminescence efficiency of the ruthenium(II) complexes
      was explained based on the ligand environment around the metal ion. These
      complexes catalyze oxidation of primary and secondary alcohols into their
      corresponding carbonyl compounds in the presence of N-methylmorpholine-N-oxide
      (NMO) as the source of oxygen. The formation of high valent Ru(IV)=O species as a
      catalytic intermediate is proposed for the catalytic process.

PMID- 16949338
TI  - Properties of a federated epidemiology query system.
AB  - PURPOSE: The purpose of the study was to establish knowledge about how online
      access to epidemiological data from general practitioners (GPs) electronic health
      record (EHR) system should be provided. Before such systems are developed and
      deployed a decision about the appropriate system architecture must be made. Such
      a decision should ideally be based on knowledge about the properties of different
      system architectures. This choice is important because the system architecture
      may affect the willingness of GPs to participate in providing epidemiological
      data from their EHR system. METHOD: Verifying the performance and properties of
      an architectural approach by implementing and deploying a system on a trans
      institutional level and performing evaluations studies is a very resource
      demanding method to establish a foundation for the decision of appropriate system
      architecture. Instead, we have tried to create this foundation by constructing a
      prototype system, establish knowledge about the properties of the system using
      experiments, and finally compare the properties of the federated approach to the
      properties of the centralised approach. By using this methodological approach we
      provide the best available knowledge, on this stage, for the appropriate system
      architecture to use for providing access to epidemiological data from the local
      population. RESULTS: Our experimental results show that it is possible to improve
      the timeliness and the temporal and spatial resolution of epidemiological data,
      compared to traditional centralised disease surveillance systems. Up-to-date
      epidemiological data from the local population may be provided directly from the
      source EHR system within 4s. The responsiveness of the system is minimally
      affected (0.1s) as the number of participating data providers grows from 1 to 49
      data providers. The comparison of the federated approach to the centralised
      approach indicates that federated approaches avoid the privacy issues involved,
      as intended; it offers better scalability when computing speed is compared, and
      it provides better specificity because more data about the patient may be used.
      CONCLUSION: The conclusion from our study is that the federated approach to
      providing epidemiological data about the local population has many benefits over
      the traditional centralised approach. A federated approach to an epidemiology
      system may raise the GPs awareness of local disease outbreak because it is
      possible to share information about incidence rates of communicable diseases and
      use of laboratory requests in a geographical area that predates laboratory-based
      disease surveillance. The effects of the federated approach could be improved
      data quality in the EHR systems and improved representativeness of the
      epidemiological data for the areas covered by such systems.

PMID- 16949339
TI  - Dimensional complexity of neuromagnetic activity reduced during finger movement
      of greater difficulty.
AB  - OBJECTIVE: We investigated the variation in dimensionality (D2) of neuromagnetic
      activity over the primary sensorimotor cortex (SM1) in healthy adults performing
      motor tasks of different difficulty. METHODS: Magnetoencephalography (MEG) was
      used to record neuromagnetic activity during self-paced, brisk unimanual finger
      extension at a rate of 1 and 2 Hz using the index finger of the dominant and non
      dominant hands in 16 healthy subjects. Motor task difficulty was rated by the
      relative difference in time measurement between 1 and 2 Hz finger movements of
      both hands. The relative difference in dimensionality of SM1 activity was
      calculated by subtracting the D2 value in 2 Hz movement from that in 1 Hz one
      within subjects. RESULTS: Simple regression analyses show a significantly
      negative relationship between the relative dimensional complexity and the
      relative motor task difficulty in the contralateral SM1 for the left- (p<0.05),
      but not the right- (p=0.447) hand movement. CONCLUSIONS: The present data suggest
      that a motor task of greater difficulty may engender a reduction of
      simultaneously active quasi-independent neuronal generators in the contralateral
      SM1 underpinned by stronger neuronal connectivity of a relatively low
      dimensionality. SIGNIFICANCE: The decrease in dimensional complexity of MEG
      activity associated with a motor task of greater difficulty gives new insights to
      motor control strategy.

PMID- 16949340
TI  - Individual variability, end-point effects and possible biases in
      electrophysiological research.
AB  - Neocortical dynamics and signals reflect spatiotemporal cortical synchronization
      as well as functional condition and modulation by subcortical projecting
      structures that determine the brain state. However, neurotransmitters interact
      and neuronal function and signals also reflect non-neuronal factors that should
      (but not necessarily are, or can) be taken into proper consideration in
      neuroscience. Examples in this regard are the CNS modulation by spontaneous or
      induced changes in metabolism (e.g. glucose, ammonia), blood flow, pO(2), pCO(2),
      hormones (thyroxine; sexual hormones, ATCH) and neurohormonal interaction,
      maturation, aging, temperature, light-dark regulation of serotonine, histamine
      and dopamine/melatonin/vitamin B12 secretion and interaction, etc. Hormones also
      regulate the (functional) maturation and differentiation between sexes both
      during development and in adult life. These factors interact with each other and
      individually or collectively can account for unexplained or underestimated
      individual variability; on occasions, may become critical variables in animal or
      human research. In specific instances, variability is the information of
      interest. However, physiological variability due to neuronal or non-neuronal
      factors can interact with the experimental setups or affect electrophysiological
      signals to extents that can result in biased findings in otherwise controlled
      studies. An "inverse problem" difficult to approach may ensue in both animal and
      human research; in several instances, the specificity of brain signals for the
      investigated function may require experimental validation.

PMID- 16949341
TI  - Modulation of the withdrawal reflex during hemiplegic gait: effect of stimulation
      site and gait phase.
AB  - OBJECTIVE: The objective of the study was to investigate the sensitivity of the
      nociceptive withdrawal reflex to stimulation of different locations on the sole
      of the foot during hemiplegic gait. METHODS: Reflexes were evoked by cutaneous
      electrical stimulation of 4 locations on the sole of the foot of 7 hemiplegic and
      6 age-matched healthy persons. The stimuli were delivered at heel-contact, during
      foot-flat, at heel-off, and during mid-swing. Reflexes were recorded from muscles
      of the stimulated and the contralateral leg. Ankle, knee, and hip joints angles
      were recorded using goniometers. RESULTS: In the hemiplegic persons, the size of
      tibialis anterior reflexes, and the latency of soleus reflexes were site- and
      phase-modulated. In both groups, the tibialis anterior reflexes were
      significantly smaller with stimulation to the fifth metatarsophalangeal joint and
      the heel compared with the first metatarsophalangeal joint and the arch of the
      foot. The tibialis anterior reflexes evoked at heel-off and mid-swing were larger
      in hemiplegic persons than in healthy persons. Reflexes in the proximal and
      contralateral limb muscles were not site-modulated during hemiplegic gait. The
      kinematic response at the ankle joint was also different in the two groups during
      mid-swing. CONCLUSIONS: Hemiplegic and healthy middle-aged people presented
      different phase-modulation of the kinematic and muscle nociceptive reflex
      responses evoked by stimulation delivered on the sole of the foot. SIGNIFICANCE:
      The results have potential application in programs to rehabilitate hemiplegic
      gait.

PMID- 16949342
TI  - Use of genotypic selection to detect P53 codon 273 CGT>CTT transversion:
      application to an occupationally exposed population.
AB  - CGT>CTT transversion in codon 273 of the P53 tumor-suppressor gene is one of the
      major mutations detected in human tumors. Within an epidemiological framework, we
      investigated the use of a genotypic selection method to measure this point
      mutation. The allele-specific polymerase chain reaction (AS-PCR) that was
      developed was able to detect 10 mutant copies of the gene among a total of 5 x
      10(5) wild-type copies. We used this assay to detect CGT>CTT transversions in
      buccal cell DNA of production workers (n=76) from a viscose factory exposed to
      carbon disulfide (amongst other pollutants) and in the DNA of non-exposed office
      workers (n=67). The mutation appeared more frequently in the exposed than in the
      non-exposed worker who were smokers. The results of the study indicate that
      occupational exposure results in a significant increase in P53 CGT>CTT
      transversions and more especially identified occupational exposure in combination
      with smoking as a significant risk factor for the mutation. We conclude that AS
      PCR of the P53 273rd codon transversions is a suitable technique for studying the
      effects of occupational exposure.

PMID- 16949343
TI  - HSV-mediated delivery of erythropoietin restores dopaminergic function in MPTP
      treated mice.
AB  - To investigate the neuroprotective effects of erythropoietin (EPO) in a rodent
      model of Parkinson disease, we inoculated a nonreplicating herpes simplex virus
      based vector expressing EPO (vector DHEPO) into the striatum of mice 1 week prior
      to, or 2 weeks after, the start of continual administration of 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) (4 mg/kg intraperitoneally, 5 of 7 days) for 6
      weeks. Inoculation with DHEPO prior to MPTP intoxication preserved behavioral
      function measured by pellet retrieval and the histological markers of tyrosine
      hydroxylase-immunoreactive (TH-IR) neuronal cell bodies in the substantia nigra
      (SN) and TH-IR and dopamine transporter-immunoreactive (DAT-IR) terminals in
      striatum. Inoculation of DHEPO 2 weeks into a 6-week course of MPTP resulted in
      improvement of behavioral function and restoration of TH-IR cells in SN and TH-
      and DAT-IR in the striatum. The effects of vector-produced EPO were similar in
      magnitude to the effects of vector-mediated expression of glial-derived
      neurotrophic factor in the same model. These results demonstrate that vector
      mediated EPO production may be used to reverse dopaminergic neurodegeneration in
      the face of continued toxic insult.

PMID- 16949344
TI  - Neuropsychological and psychiatric impact of add-on titration of pregabalin
      versus levetiracetam: a comparative short-term study.
AB  - Cognitive and behavioral impairments are common in patients with epilepsy.
      Multiple factors may contribute to these difficulties; among them is
      antiepileptic drug (AED) treatment. We examined the short-term impact of two new
      add-on AEDs, pregabalin (PGB) and levetiracetam (LEV), on cognition and
      psychiatric states in 20 adult patients with medically refractory partial
      epilepsy, before and shortly after add-on titration. According to an open,
      prospective comparative trial, add-on PGB was titrated to 300 mg and add-on LEV
      to 1000 mg in 10 patients each. Patients were assessed before (T1) and 2 weeks
      after (T2) addition of the AED. During the trial, seizure frequency did not
      change significantly in either group. With PGB, patients manifested partly
      significant impairments in episodic memory of verbal and visual information.
      Psychiatric states were unchanged. With LEV treatment, we saw improvements in
      visual short-term memory performance and psychiatric states (i.e., interpersonal
      sensibility, depression, and anxiety). The comparison between PGB and LEV
      revealed a trend toward higher anxiety scores and higher variability in hostility
      scores with PGB that was significantly different from the trend with LEV. No
      significant differences were apparent in all other neuropsychological and
      psychiatric parameters investigated. This short-term study suggests that add-on
      LEV has a favorable neuropsychological and psychiatric impact. The negative
      neuropsychological effects of PGB may reflect temporary effects under titration.
      Still, the results did not confirm the promising effects on psychiatric
      comorbidity that have been emphasized by other reports.

PMID- 16949345
TI  - Cell and molecular biology of SAE, a cell line from the spiny dogfish shark,
      Squalus acanthias.
AB  - Cartilaginous fish, primarily sharks, rays and skates (elasmobranchs), appeared
      450 million years ago. They are the most primitive vertebrates, exhibiting jaws
      and teeth, adaptive immunity, a pressurized circulatory system, thymus, spleen,
      and a liver comparable to that of humans. The most used elasmobranch in
      biomedical research is the spiny dogfish shark, Squalus acanthias. Comparative
      genomic analysis of the dogfish shark, the little skate (Leucoraja erincea), and
      other elasmobranchs have yielded insights into conserved functional domains of
      genes associated with human liver function, multidrug resistance, cystic
      fibrosis, and other biomedically relevant processes. While genomic information
      from these animals is informative in an evolutionary framework, experimental
      verification of functions of genomic sequences depends heavily on cell culture
      approaches. We have derived the first multipassage, continuously proliferating
      cell line of a cartilaginous fish. The line was initiated from embryos of the
      spiny dogfish shark. The cells were maintained in a medium modified for fish
      species and supplemented with cell type-specific hormones, other proteins and
      sera, and plated on a collagen substrate. SAE cells have been cultured
      continuously for three years. These cells can be transfected by plasmids and have
      been cryopreserved. Expressed Sequence Tags generated from a normalized SAE cDNA
      library included a number of markers for cartilage and muscle, as well as
      proteins influencing tissue differentiation and development, suggesting that SAE
      cells may be of mesenchymal stem cell origin. Examination of SAE EST sequences
      also revealed a cartilaginous fish-specific repetitive sequence that may be
      evidence of an ancient mobile genetic element that most likely was introduced
      into the cartilaginous fish lineage after divergence from the lineage leading to
      teleosts.

PMID- 16949346
TI  - A new approach to the assessment of the quality of predictions of transcription
      factor binding sites.
AB  - In this paper, we describe a novel method called Secondary Verification which
      assesses the quality of predictions of transcription factor binding sites. This
      method incorporates a distribution of prediction scores over positive examples
      (i.e. the actual binding sites) and is shown to be superior to p-value, routinely
      used statistical significance assessment, which uses only a distribution of
      prediction scores over background sequences. We also discuss how to integrate
      both distributions into a framework called Secondary Verification Assessment
      method which evaluates the quality of a model of a transcription factor. Based on
      that we create a hybrid representation of a transcription factor: we select the
      description (with or without dependencies) which is best for the transcription
      factor considered.

PMID- 16949347
TI  - Gastroenterology and hepatology clinical research update: 2005-2006.
AB  - This review highlights areas of clinical research in gastroenterology and
      hepatology that were published predominantly in the journal Clinical
      Gastroenterology and Hepatology during the last year and were summarized during
      the American Gastroenterological Association Presidential Plenary Session in May
      2006. The topics included eosinophilic esophagitis in children, detecting high
      grade dysplasia or carcinoma in Barrett's esophagus, advances in management of
      celiac disease with elemental diet or gluten predigestion, the safety of NSAIDs
      in inflammatory bowel disease, the role of steroids in development of abscesses,
      prognosis of colorectal cancer associated with inflammatory bowel disease,
      screening for familial colorectal cancer in apparently sporadic disease, a new
      syndrome of familial colorectal cancer, new drugs in the treatment of chronic
      constipation and obesity, hepatoma risk factors and underserved racial/ethnic
      groups, and the application of new imaging and biology in diagnosis of
      gastroenterological disorders.

PMID- 16949348
TI  - Recruitment of the elderly into a pharmacologic prevention trial: the Ginkgo
      Evaluation of Memory Study experience.
AB  - The difficulty involved in recruiting healthy older adults into clinical trials,
      especially those involving pharmacologic agents, is an important issue in
      research. The Ginkgo Evaluation of Memory (GEM) Study, a double-blind, placebo
      controlled randomized clinical trial evaluating Ginkgo biloba to prevent
      dementia, successfully recruited 3072 participants age 75 years and older at four
      U.S. sites from September 2000 through June 2002. Using targeted mailing lists,
      an estimated 243,400 study brochures were mailed out to potential participants.
      Subsequent attempts were made to reach 14,603 households by telephone, from which
      12,186 (83.4%) successful contacts were made. Overall, telephone or in-person
      evaluations identified 2149 (17.6%) ineligible persons for cognitive (20.6%),
      medical (49.4%), or other (30.0%) reasons. A total of 6944 (57.0%) refused
      participation resulting in 3072 enrolled into the study, a recruitment rate of
      25.2% based on telephone contacts made or 1.3% of all mailed brochures.
      Recruitment rates were stable over the 21-month enrollment period but were higher
      for the two urban centers than the two rural ones. Recruitment was dependent most
      on mailing lists available, density of older adults in the catchment areas, and
      Institutional Review Board restrictions. Men and persons under age 85 were more
      likely to enroll. Primary reason for refusals involved lack of interest (48.4%)
      or self-perceived poor health (16.2%). Over 9% were unwilling to give up current
      Ginkgo supplementation or would not accept assignment to placebo. An additional
      7% did not want another medication and almost 4% had care-giving responsibilities
      which prevented involvement. Mass mailings were the most successful approach for
      recruitment at all four sites and the method through which the vast majority of
      interviewees had learned about the study. Information on the experience of the
      GEM Study recruitment may be helpful to other clinical trials attempting to
      randomize older adults into prevention trials.

PMID- 16949349
TI  - Expression pattern of BM88 in the developing nervous system of the chick and
      mouse embryo.
AB  - We isolated a chick homologue of BM88 (cBM88), a cell-intrinsic nervous system
      specific protein and examined the expression of BM88 mRNA and protein in the
      developing brain, spinal cord and peripheral nervous system of the chick embryo
      by in situ hybridization and immunohistochemistry. cBM88 is widely expressed in
      the developing central nervous system, both in the ventricular and mantle zones
      where precursor and differentiated cells lie, respectively. In the spinal cord,
      particularly strong cBM88 expression is detected ventrally in the motor neuron
      area. cBM88 is also expressed in the dorsal root ganglia and sympathetic ganglia.
      In the early neural tube, cBM88 is first detected at HH stage 15 and its
      expression increases with embryonic age. At early stages, cBM88 expression is
      weaker in the ventricular zone (VZ) and higher in the mantle zone. At later
      stages, when gliogenesis persists instead of neurogenesis, BM88 expression is
      abolished in the VZ and cBM88 is restricted in the neuron-containing mantle zone
      of the neural tube. Association of cBM88 expression with cells of the neuronal
      lineage in the chick spinal cord was demonstrated using a combination of markers
      characteristic of neuronal or glial precursors, as well as markers of
      differentiated neuronal, oligodendroglial and astroglial cells. In addition to
      the spinal cord, cBM88 is expressed in the HH stage 45 (embryonic day 19) brain,
      including the telencephalon, diencephalon, mesencephalon, optic tectum and
      cerebellum. BM88 is also widely expressed in the mouse embryonic CNS and PNS, in
      both nestin-positive neuroepithelial cells and post-mitotic betaIII-tubulin
      positive neurons.

PMID- 16949350
TI  - Population genetics and molecular epidemiology or how to "debusquer la bete".
AB  - Parasites represent a great proportion of the world's living organisms and are of
      overwhelming significance because of their impact on hosts (evolutionarily,
      medically, agronomical and economically). The knowledge of the population biology
      of such organisms is thus of fundamental importance to population biologists.
      Most parasites cannot be studied by direct methods and their biology has to be
      assessed via indirect means, most notably using molecular markers. In this
      review, we present the molecular tools, the null models employed, the statistical
      tools available and the kinds of inferences one can make when using molecular
      markers to study the ecology/epidemiology of host-parasite systems (molecular
      ecology/molecular epidemiology). We conclude with relevant examples, most issued
      from our laboratory, to illustrate the pros and cons of such methods for the
      study of parasites, vectors, micropathogens and their hosts and briefly discuss
      future needs.

PMID- 16949351
TI  - The relevance of wing geometry in entomological surveillance of Triatominae,
      vectors of Chagas disease.
AB  - An important epidemiological challenge in controlling the Triatominae (Hemiptera:
      Reduviidae), vectors of Chagas disease, is identifying the origin of insects re
      infesting treated areas, especially when reinfestation occurs during the first 1
      or 2 years following insecticide application and in the absence of insecticide
      resistance. When using strict insect characteristics, the standard approach is to
      compare reinfesting specimens with those collected prior to treatment. Because of
      the long generation time of Triatominae, the experimental intent is to reject the
      hypothesis of a previous population, the one prior to insecticide application, to
      be the parental population of the reinfesting population. Biometric techniques
      are based on the hypothesis of more similarity between offspring and parents, and
      have been tested in the field. Reinfesting specimens are very few when
      discovered, which might cause sampling problems. The present study used museum
      material to test the performance of modern morphometrics to assess the origin of
      a single individual. A configuration of 13 landmarks was used to assign a single
      wing to its known parental line or relatives. For the 313 wings tested, correct
      attribution to the parental line was four times higher than expected at random.
      Moreover, most of the apparently wrong assignments were not random, but driven by
      lower levels of kinship. These results suggest that the geometry of the wing
      contains helpful information to identify the possible source of reinfesting
      specimens.

PMID- 16949352
TI  - Comparison of chaetognath mitochondrial genomes and phylogenetical implications.
AB  - Two complete mitochondrial genomes (mtDNAs) of chaetognaths, Spadella
      cephaloptera and Paraspadella gotoi, have been recently published. These genomes
      are highly unusual. They are the smallest metazoan mtDNAs so far known; atp6 and
      atp8 genes are missing; lastly, our reanalysis has evidenced that, contrarily to
      what has been previously published for one sequence, both contain a unique
      transfer RNA (tRNA(Met)) evidencing that both have the same gene content. Indeed,
      even if the gene order seems very different, two gene blocks are conserved. In
      addition, comparison of gene arrangement suggests phylogenetical relationships
      between chaetognaths and some lophotrochozoa like annelids and molluscs.

PMID- 16949353
TI  - Resistance training, and IGF involvement in the maintenance of muscle mass during
      the aging process.
AB  - Sarcopenia is the decline of muscle mass and strength with age. Sarcopenia leads
      to significant impairment in the ability to carry out normal daily function and
      thus there is a great need for interventions that will lead to muscle
      regeneration and repair in the aging population. Age-related sarcopenia in
      humans, characterized by loss of type I and type II muscle fibers and a decrease
      in fiber cross-sectional area primarily in type II fibers, can be attenuated by
      mechanical load on the muscle, which increases cross-sectional area of the
      remaining fibers, but does not restore fiber numbers characteristic of young
      muscle. Considerable evidence also implicates age-related declines in muscle
      insulin-like growth factor action in sarcopenia. IGF-I promotes myoblast
      proliferation, differentiation, and protein accretion in muscle through multiple
      signaling mechanisms, including the PI3-kinase, MAP kinase and calcineurin
      pathways. Exercise and injury induce increases in IGF-I, IGF-I receptors and IGF
      I-activated signaling pathways. Although there is evidence that aging muscle
      retains the ability to synthesize IGF-I, there is also evidence that aging may be
      associated with attenuation of the ability of exercise to induce an isoform of
      IGF-I that promotes satellite cell proliferation. Moreover, aging muscle may be
      resistant to IGF-I, an effect that is reversed by exercise. However, it is clear
      that over-expression of IGF-I in muscle can protect against age-related
      sarcopenia.

PMID- 16949354
TI  - Mgs1 and Rad18/Rad5/Mms2 are required for survival of Saccharomyces cerevisiae
      mutants with novel temperature/cold sensitive alleles of the DNA polymerase delta
      subunit, Pol31.
AB  - Saccharomyces cerevisiae DNA polymerase delta (Pol delta) is a heterotrimeric
      enzyme consisting of Pol3 (the catalytic subunit), Pol31 and Pol32. New pol31
      alleles were constructed by introducing mutations into conserved amino acid
      residues in all 10 identified regions of Pol31. Six novel temperature-sensitive
      (ts) or cold-sensitive (cs) alleles, carrying mutations in regions III, IV, VII,
      VIII or IX, conferred a range of defects in the response to replication stress or
      DNA damage. Deletion of SGS1, RAD52, SRS2, MRC1 or RAD24 had a deleterious effect
      only in combination with those pol31 alleles that had a phenotype as single
      mutants, suggesting a requirement for recombination and checkpoint functions in
      processing the DNA lesions or structures that form as a consequence of
      replication with a defective Pol delta. In contrast, deletion of POL32 negatively
      affected the growth of almost all pol31 mutants, suggesting an important role for
      all conserved amino acids of Pol31 in maintaining the integrity of Pol delta
      complex structurally, at least in the absence of the third subunit. Surprisingly,
      deletions of RAD18 and MGS1 aggravated the temperature sensitivity conferred by
      most ts or cs alleles and specifically suppressed the hys2-1 and hys2-1-like
      mutations of POL31. Deletion of RAD5 or MMS2 had an effect on pol31 ts/cs mutants
      similar to that of RAD18, whereas deletion of RAD30 or REV3 had no effect. We
      propose that Rad18/Rad5/Mms2 and Mgs1 are required to promote replication when
      forks are destabilized or stalled due to defects in Pol delta. These data are
      consistent with the biochemical activity of the human Mgs1 orthologue, which
      binds and stimulates Pol deltain vitro. We also demonstrate that Mgs1 interacts
      physically with Pol31 in vivo. Moreover, regions I and VII of Pol31, which are
      specifically sensitive to high levels of Mgs1 and PCNA, could be sites of
      interaction.

PMID- 16949355
TI  - Challenging midwifery care, challenging midwives and challenging the system.
AB  - The purpose of this paper is to generate debate and discussion about the state of
      midwifery services in Australia today. While numerous reports have been published
      that highlight what women want in maternity care, widespread change has not
      occurred. This paper presents the story of Alice (a real woman with a fictitious
      name). Alice's story highlights the challenges that women face in dealing with a
      system that is often inflexible. While the health systems, and those who work
      within them, usually have the best intentions to try to provide the type of care
      that women want, they are not always successful. The paper summarises the
      evidence and support for models of continuity of midwifery care and outlines a
      series of strategies to ensure that change can occur. Finally, the paper
      challenges all midwives to work towards widespread, system-level change in
      Australian maternity services.

PMID- 16949356
TI  - Specimen-specific beam models for fast and accurate prediction of human
      trabecular bone mechanical properties.
AB  - Direct assessment of bone competence in vivo is not possible, hence, it is
      inevitable to predict it using appropriate simulation techniques. Although
      accurate estimates of bone competence can be obtained from micro-finite element
      models (muFE), it is at the expense of large computer efforts. In this study, we
      investigated the application of structural idealizations to represent individual
      trabeculae by single elements. The objective was to implement and validate this
      technique. We scanned 42 human vertebral bone samples (10 mm height, 8 mm
      diameter) with micro-computed tomography using a 20 microm resolution. After
      scanning, direct mechanical testing was performed. Topological classification and
      dilation-based algorithms were used to identify individual rods and plates. Two
      FE models were created for each specimen. In the first one, each rod-like
      trabecula was modeled with one thickness-matched beam; each plate-like trabecula
      was modeled with several beams. From a simulated compression test, assuming one
      isotropic tissue modulus for all elements, the apparent stiffness was calculated.
      After reducing the voxel size to 40 microm, a second FE model was created using a
      standard voxel conversion technique. Again, one tissue modulus was assumed for
      all elements in all models, and a compression test was simulated. Bone volume
      fraction ranged from 3.7% to 19.5%; Young's moduli from 43 MPa to 649 MPa. Both
      models predicted measured apparent moduli equally well (R2 = 0.85), and were in
      excellent agreement with each other (R2 = 0.97). Tissue modulus was estimated at
      9.0 GPa and 10.7 GPa for the beam FE and voxel FE models, respectively. On
      average, the beam models were solved in 219 s, reducing CPU usage up to 1150-fold
      as compared to 40 microm voxel FE models. Relative to 20 microm voxel models
      10,000-fold reductions can be expected. The presented beam FE model is an
      abstraction of the intricate real trabecular structure using simple cylindrical
      beam elements. Nevertheless, it enabled an accurate prediction of global
      mechanical properties of microstructural bone. The strong reduction in CPU time
      provides the means to increase throughput, to analyze multiple loading
      configuration and to increase sample size, without increasing computational
      costs. With upcoming in vivo high-resolution imaging systems, this model has the
      potential to become a standard for mechanical characterization of bone.

PMID- 16949357
TI  - Re: "Half the burden of fragility fractures in the community occur in women
      without osteoporosis. When is fracture prevention cost effective?" by Sanders et
      al.

PMID- 16949358
TI  - Glucocorticoids induce the differentiation of a mesenchymal progenitor cell line,
      ROB-C26 into adipocytes and osteoblasts, but fail to induce terminal osteoblast
      differentiation.
AB  - To clarify the effects of glucocorticoids (GCs) on osteoblast and adipocyte
      differentiation, we investigated the effects of dexamethasone (Dex), a GC
      analogue on transcription factors for osteoblasts (Runx2, Dlx5 and Osterix) and
      adipocytes (C/EBPs such as C/EBPalpha, C/EBPbeta and C/EBPdelta, and PPARgamma2),
      late osteoblastic markers, bone sialoprotein (BSP) and osteocalcin (OC), and
      adipocyte differentiation-dependent protein, aP2 in a clonal mesenchymal
      progenitor cell line, ROB-C26 (C26). C26 cells were dose- and time-dependently
      responsive to Dex in terms of an increase in not only mRNA and protein
      expressions of the C/EBPs, PPARgamma2 and aP2, but also Runx2, Dlx5, BSP and OC
      with no induction of Osterix, which is considered to act mainly on terminal
      osteoblast differentiation. Cycloheximide pretreatment indicated that Dex
      signaling immediately increases expressions of the C/EBPs and Dlx5, while
      expressions of the rest of the genes require de novo protein synthesis.
      Continuous Dex treatment stimulated adipocyte formation, but failed to induce
      Osterix expression and mineralized matrix formation. However, BMP-2 treatment of
      Dex-treated cells induced Osterix expression and subsequent mineralized matrix
      formation. These results indicate that Dex up-regulates the C/EBPs followed by
      increasing PPARgamma2 and aP2 expressions in C26 cells to induce adipocyte
      differentiation, while Dex enhances Dlx5 followed by increasing Runx2, BSP and OC
      expressions at gene and protein levels, but cannot induce Osterix expression,
      suggesting that Dex does not promote their terminal osteoblast differentiation.

PMID- 16949359
TI  - Quantitative Ultrasound--it is time to focus research efforts.
AB  - Quantitative Ultrasound (QUS) methods show great potential for refined assessment
      of bone strength. However, for widespread clinical acceptance, three issues have
      to be resolved: Will patients with low QUS readings benefit from approved
      osteoporosis medications? How can we ensure good quality of QUS measurements in
      daily clinical practice? How much added value does QUS bring to risk factor based
      case-finding strategies? When addressing these issues, differences among QUS
      approaches need to be recognized and vague and misleading terminology, e.g.,
      regarding bone quality assessment, needs to be avoided. Innovations including
      assessment of material or micro-structural properties and direct QUS measurements
      at the proximal femur are likely to spark additional interest in pursuing QUS
      research.

PMID- 16949360
TI  - Cell signaling and function organized by PB1 domain interactions.
AB  - The PB1-domain-containing proteins p62, aPKC, MEKK2/MEKK3, MEK5, and Par-6 play
      roles in critical cell processes like osteoclastogenesis, angiogenesis, and early
      cardiovascular development or cell polarity. PB1 domains are scaffold modules
      that adopt the topology of ubiquitin-like beta-grasp folds that interact with
      each other in a front-to-back mode to arrange heterodimers or homo-oligomers. The
      different PB1 domain adaptors provide specificity for PB1 kinases to ensure the
      effective transmission of cellular signals. Also, recent data suggest that PB1
      domains may serve to orchestrate signaling cascades not involving other PB1
      domains, such as the MEK5-ERK5 and p62-ERK1 interactions.

PMID- 16949361
TI  - L-type Ca2+ channel facilitation mediated by phosphorylation of the beta subunit
      by CaMKII.
AB  - L-type Ca(2+) channels (LTCCs) are major entry points for Ca(2+) in many cells.
      Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is associated with cardiac
      LTCC complexes and increases channel open probability (P(O)) to dynamically
      increase Ca(2+) current (I(Ca)) and augment cellular Ca(2+) signaling by a
      process called facilitation. However, the critical molecular mechanisms for
      CaMKII localization to LTCCs and I(Ca) facilitation in cardiomyocytes have not
      been defined. We show CaMKII binds to the LTCC beta(2a) subunit and
      preferentially phosphorylates Thr498 in beta(2a). Mutation of Thr498 to Ala
      (T498A) in beta(2a) prevents CaMKII-mediated increases in the P(O) of recombinant
      LTCCs. Moreover, expression of beta(2a)(T498A) in adult cardiomyocytes ablates
      CaMKII-mediated I(Ca) facilitation, demonstrating that phosphorylation of
      beta(2a) at Thr498 modulates native calcium channels. These findings reveal a
      molecular mechanism for targeting CaMKII to LTCCs and facilitating I(Ca) that may
      modulate Ca(2+) entry in diverse cell types coexpressing CaMKII and the beta(2a)
      subunit.

PMID- 16949362
TI  - Type IV pilus structure by cryo-electron microscopy and crystallography:
      implications for pilus assembly and functions.
AB  - Type IV pili (T4P) are long, thin, flexible filaments on bacteria that undergo
      assembly-disassembly from inner membrane pilin subunits and exhibit astonishing
      multifunctionality. Neisseria gonorrhoeae (gonococcal or GC) T4P are prototypic
      virulence factors and immune targets for increasingly antibiotic-resistant human
      pathogens, yet detailed structures are unavailable for any T4P. Here, we
      determined a detailed experimental GC-T4P structure by quantitative fitting of a
      2.3 A full-length pilin crystal structure into a 12.5 A resolution native GC-T4P
      reconstruction solved by cryo-electron microscopy (cryo-EM) and iterative helical
      real space reconstruction. Spiraling three-helix bundles form the filament core,
      anchor the globular heads, and provide strength and flexibility. Protruding
      hypervariable loops and posttranslational modifications in the globular head
      shield conserved functional residues in pronounced grooves, creating a
      surprisingly corrugated pilus surface. These results clarify T4P
      multifunctionality and assembly-disassembly while suggesting unified assembly
      mechanisms for T4P, archaeal flagella, and type II secretion system filaments.

PMID- 16949363
TI  - Key interaction modes of dynamic +TIP networks.
AB  - Dynamic microtubule plus-end tracking protein (+TIP) networks are implicated in
      all functions of microtubules, but the molecular determinants of their
      interactions are largely unknown. Here, we have explored key binding modes of
      +TIPs by analyzing the interactions between selected CAP-Gly, EB-like, and
      carboxy-terminal EEY/F-COO(-) sequence motifs. X-ray crystallography and
      biophysical binding studies demonstrate that the beta2-beta3 loop of CAP-Gly
      domains determines EB-like motif binding specificity. They further show how CAP
      Gly domains serve as recognition domains for EEY/F-COO(-) motifs, which represent
      characteristic and functionally important sequence elements in EB, CLIP-170, and
      alpha-tubulin. Our findings provide a molecular basis for understanding the
      modular interaction modes between alpha-tubulin, CLIPs, EB proteins, and the
      dynactin-dynein motor complex and suggest that multiple low-affinity binding
      sites in different combinations control dynamic +TIP networks at microtubule
      ends. They further offer insights into the structural consequences of genetic CAP
      Gly domain defects found in severe human disorders.

PMID- 16949364
TI  - A spliceosomal intron binding protein, IBP160, links position-dependent assembly
      of intron-encoded box C/D snoRNP to pre-mRNA splicing.
AB  - Pre-mRNA splicing in vertebrates is molecularly linked to other processes. We
      previously reported that splicing is required for efficient assembly of intron
      encoded box C/D small nucleolar ribonucleoprotein (snoRNP). In the spliceosomal
      C1 complex, snoRNP proteins efficiently assemble onto snoRNA sequences if they
      are located about 50 nt upstream of the intron branchpoint. Here, we identify the
      splicing factor responsible for coupling snoRNP assembly to intron excision.
      Intron binding protein (IBP) 160, a helicase-like protein previously detected in
      the spliceosomal C1 complex, binds the pre-mRNA in a sequence-independent manner,
      contacting nucleotides 33-40 upstream of the intron branch site, regardless of
      whether a snoRNA is present. Depletion of IBP160 abrogates snoRNP assembly in
      vitro. IBP160 binding directly to a snoRNA located too close to the intron branch
      site interferes with snoRNP assembly. Thus, IBP160 is the key factor linking
      snoRNP biogenesis and perhaps other postsplicing events to pre-mRNA splicing.

PMID- 16949365
TI  - Nuclear PtdIns5P as a transducer of stress signaling: an in vivo role for
      PIP4Kbeta.
AB  - Inhibitor of growth protein-2 (ING2) is a nuclear adaptor protein that can
      regulate p53 and histone acetylation in response to cellular stress and contains
      a PHD (plant homeodomain) finger that can interact with phosphatidylinositol-5
      phosphate (PtdIns5P). However, whether or how nuclear PtdIns5P levels are
      regulated in response to cellular stress or whether ING2 can sense these changes
      has not been demonstrated. We show that UV irradiation increases nuclear PtdIns5P
      levels via inhibition of the activity of the beta isoform of PtdIns5P 4-kinase
      (PIP4Kbeta), an enzyme that can phosphorylate and remove PtdIns5P. Inhibition of
      PIP4Kbeta activity occurs through the direct phosphorylation of PIP4Kbeta at
      Ser326 by the p38 stress-activated protein kinase. Finally, we show that changes
      in nuclear PtdIns5P are translated into changes in the association of ING2 with
      chromatin. Our data define a pathway connecting cellular stressors with changes
      in nuclear PtdIns5P levels and the regulation of PHD motif-containing proteins.

PMID- 16949366
TI  - Structure of an Hsp90-Cdc37-Cdk4 complex.
AB  - Activation of many protein kinases depends on their interaction with the Hsp90
      molecular chaperone system. Recruitment of protein kinase clients to the Hsp90
      chaperone system is mediated by the cochaperone adaptor protein Cdc37, which acts
      as a scaffold, simultaneously binding protein kinases and Hsp90. We have now
      expressed and purified an Hsp90-Cdc37-Cdk4 complex, defined its stoichiometry,
      and determined its 3D structure by single-particle electron microscopy.
      Comparison with the crystal structure of Hsp90 allows us to identify the
      locations of Cdc37 and Cdk4 in the complex and suggests a mechanism by which
      conformational changes in the kinase are coupled to the Hsp90 ATPase cycle.

PMID- 16949367
TI  - A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is
      required for S phase destruction of the replication factor Cdt1.
AB  - Cul4 E3 ubiquitin ligases contain the cullin 4 scaffold and the triple beta
      propeller Ddb1 adaptor protein, but few substrate receptors have been identified.
      Here, we identify 18 Ddb1- and Cul4-associated factors (DCAFs), including 14
      containing WD40 repeats. DCAFs interact with multiple surfaces on Ddb1, and the
      interaction of WD40-containing DCAFs with Ddb1 requires a conserved "WDXR" motif.
      DCAF2/Cdt2, which is related to S. pombe Cdt2, functions in Xenopus egg extracts
      and human cells to destroy the replication licensing protein Cdt1 in S phase and
      after DNA damage. Depletion of human Cdt2 causes rereplication and checkpoint
      activation. In Xenopus, Cdt2 is recruited to replication forks via Cdt1 and PCNA,
      where Cdt1 ubiquitylation occurs. These studies uncover diverse substrate
      receptors for Cul4 and identify Cdt2 as a conserved component of the Cul4-Ddb1 E3
      that is essential to destroy Cdt1 and ensure proper cell cycle regulation of DNA
      replication.

PMID- 16949368
TI  - CTCF-dependent chromatin insulator is linked to epigenetic remodeling.
AB  - Chromatin insulators are boundary elements between distinctly regulated,
      neighboring chromosomal domains, and they function by blocking the effects of
      nearby enhancers in a position-dependent manner. Here, we show that the SNF2-like
      chromodomain helicase protein CHD8 interacts with the insulator binding protein
      CTCF. Chromatin immunoprecipitation analysis revealed that CHD8 was present at
      known CTCF target sites, such as the differentially methylated region (DMR) of
      H19, the locus control region of beta-globin, and the promoter region of BRCA1
      and c-myc genes. RNA interference-mediated knockdown of CHD8 significantly
      abolished the H19 DMR insulator activity that depends highly on CTCF, leading to
      reactivation of imprinted IGF2 from chromosome of maternal origin. Further, the
      lack of CHD8 affected CpG methylation and histone acetylation around the CTCF
      binding sites, adjacent to heterochromatin, of BRCA1 and c-myc genes. These
      findings provide insight into the role of CTCF-CHD8 complex in insulation and
      epigenetic regulation at active insulator sites.

PMID- 16949369
TI  - Mycobacteriophage exploit NHEJ to facilitate genome circularization.
AB  - Ku-dependent nonhomologous end joining (NHEJ) is a double-strand break repair
      process conserved in all branches of cellular life but has not previously been
      implicated in the DNA metabolic processes of viruses. We identified Ku homologs
      in Corndog and Omega, two related mycobacteriophages of Mycobacterium smegmatis.
      These proteins formed homodimers and bound DNA ends in a manner identical to
      other Ku's and stimulated joining of ends by the host NHEJ DNA ligase (LigD).
      Omega and Corndog are unusual in having short 4 base cos ends that would not be
      expected to self-anneal and would therefore require NHEJ during phage genome
      circularization. Consistently, M. smegmatis LigD null strains are entirely and
      selectively unable to support infection by Corndog or Omega, with concomitant
      failure of genome circularization. These results establish a new paradigm for
      sequestration of the host cell NHEJ process by bacteriophage and provide a
      framework for understanding similar transactions in eukaryotic viral infections.

PMID- 16949370
TI  - Nuclear myosin VI enhances RNA polymerase II-dependent transcription.
AB  - Myosin VI is the only myosin that moves toward the minus end of actin filaments,
      suggesting a unique biological function. Here, we show that myosin VI is present
      in the nucleus of mammalian cells where it colocalizes with newly transcribed
      mRNA and with RNA polymerase II (RNAPII) and is detected in the RNAPII complex.
      The colocalization and interaction of myosin VI with RNAPII require
      transcriptional activity. Chromatin immunoprecipitation (ChIP) demonstrates that
      myosin VI is recruited to the promoter and intragenic regions of active genes,
      encoding urokinase plasminogen activator (uPA), eukaryotic initiation factor 6
      (p27/eIF6), and low-density lipoprotein receptor (LDLR), but not to noncoding,
      nonregulatory intergenic regions. Downregulation of myosin VI reduces steady
      state mRNA levels of these genes in vivo, and antibodies to myosin VI reduce
      transcription in vitro. We suggest that myosin VI modulates RNAPII-dependent
      transcription of active genes, implicating the possibility of an actin-myosin
      based mechanism of transcription.

PMID- 16949371
TI  - Wip1 phosphatase modulates ATM-dependent signaling pathways.
AB  - Deletion of Ppm1d, the gene encoding the Wip1 phosphatase, renders cells
      resistant to transformation and mice resistant to tumor development. Here, we
      report that deficiency of Wip1 resulted in activation of the ataxia
      telangiectasia mutated (ATM) kinase. In turn, overexpression of Wip1 was
      sufficient to reduce activation of the ATM-dependent signaling cascade after DNA
      damage. Wip1 dephosphorylated ATM Ser1981, a site critical for ATM monomerization
      and activation, and was critical for resetting ATM phosphorylation as cells
      repaired damaged DNA. We propose that the Wip1 phosphatase is an integral
      component of an ATM-dependent signaling pathway.

PMID- 16949372
TI  - Acyl-phosphates initiate membrane phospholipid synthesis in Gram-positive
      pathogens.
AB  - It is not known how Gram-positive bacterial pathogens carry out glycerol-3
      phosphate (G3P) acylation, which is the first step in the formation of
      phosphatidic acid, the key intermediate in membrane phospholipid synthesis. In
      Escherichia coli, acylation of the 1-position of G3P is carried out by PlsB;
      however, the majority of bacteria lack a plsB gene and in others it is not
      essential. We describe a two-step pathway that utilizes a new fatty acid
      intermediate for the initiation of phospholipid formation. First, PlsX produces a
      unique activated fatty acid by catalyzing the synthesis of fatty acyl-phosphate
      from acyl-acyl carrier protein, and then PlsY transfers the fatty acid from acyl
      phosphate to the 1-position of G3P. The PlsX/Y pathway defines the most widely
      distributed pathway for the initiation of phospholipid formation in bacteria and
      represents a new target for the development of antibacterial therapeutics.

PMID- 16949375
TI  - Epidemiology and prognostic implications of contrast-induced nephropathy.
AB  - Contrast-induced nephropathy (CIN), usually defined as an increase in serum
      creatinine of 0.5 mg/dL (44.2 mumol/L), or a 25% increase from the baseline value
      48 hours after the procedure, is a common and potentially serious complication of
      the use of iodinated contrast media in patients at risk of acute renal injury. It
      is an important cause of hospital-acquired renal failure, responsible for
      approximately 11% of cases. CIN may be difficult to distinguish from cholesterol
      embolization, another cause of postprocedure renal impairment. The reported
      incidence of CIN varies depending on the patient population studied. The impact
      of postprocedural renal impairment on clinical outcomes has been evaluated most
      extensively in patients undergoing percutaneous coronary intervention. CIN is
      associated with increased mortality both in hospital and at 1 year. A higher
      incidence of in-hospital and late cardiovascular events, as well as longer
      hospital stays, has been reported in patients developing CIN. In a small
      proportion of patients, CIN is severe enough to require dialysis, and these
      patients have a particularly poor prognosis. Many of the risk markers for CIN are
      also predictive of a worse prognosis.

PMID- 16949376
TI  - Pathophysiology of contrast-induced nephropathy.
AB  - Contrast-induced nephropathy (CIN) is the third leading cause of acute kidney
      injury in hospitalized patients and is associated with significant patient
      morbidity. The pathogenesis of CIN is complex and not fully understood, but
      iodinated contrast agents induce intense and prolonged vasoconstriction at the
      corticomedullary junction of the kidney. Moreover, high-osmolar dyes directly
      impair the autoregulatory capacity of the kidney through a loss of nitric oxide
      production. These effects, coupled with direct tubular toxicity of contrast
      media, lead to overt acute tubular necrosis and the syndrome of CIN.

PMID- 16949377
TI  - Baseline renal function screening.
AB  - Renal impairment at baseline (estimated glomerular filtration rate [eGFR] <60
      mL/min/1.73 m(2)) is the most important risk marker to predict the risk of
      contrast-induced nephropathy (CIN) in patients receiving iodinated contrast
      media. Hence, it is important to assess renal function before administration of
      contrast medium to ensure that appropriate steps are taken to reduce the risk.
      Serum creatinine alone does not provide a reliable measure of renal function,
      hence the National Kidney Foundation Kidney Disease Outcome Quality Initiative
      (K/DOQI) recommends that clinicians should use an eGFR calculated from the serum
      creatinine as an index of renal function. The CIN Consensus Working Panel agreed
      that eGFR should be determined before contrast administration, using the
      abbreviated Modification of Diet in Renal Disease (MDRD) formula, recommended by
      K/DOQI as the preferred equation for the calculation of eGFR in adults. Where a
      serum creatinine measurement or eGFR is not available, a simple survey or
      questionnaire can be used before contrast agent administration to identify
      patients at higher risk for CIN compared with the general population. In
      emergency situations, where the benefit of very early imaging outweighs the risk
      of waiting, the CIN Consensus Working Panel agreed that the procedure can be
      performed without assessment of renal function.

PMID- 16949378
TI  - Risk prediction of contrast-induced nephropathy.
AB  - In order to make appropriate decisions about clinical management, it is important
      for physicians to be able to stratify patients according to their risk for
      contrast-induced nephropathy (CIN). The most important risk marker for
      nephropathy after exposure to iodinated contrast media is preexisting renal
      impairment. The risk of CIN is elevated and becomes clinically important in
      patients with chronic kidney disease characterized by an estimated glomerular
      filtration rate <60 mL/min per 1.73 m(2). In patients with renal impairment,
      diabetes mellitus amplifies the risk of CIN and complicates postprocedure
      management. Other markers associated with an increased risk of CIN include
      cardiovascular disease, periprocedural hemodynamic instability, use of
      nephrotoxic drugs, and anemia. The effect of risk factors is additive, and the
      presence of multiple risk factors in the same patient can create a very high risk
      for CIN and acute renal failure requiring dialysis. Risk models incorporating
      baseline and periprocedural characteristics have been developed using data from
      large databases of percutaneous coronary intervention patients. These schemes are
      potentially valuable, but at present the most practical approach to risk
      prediction is based on a simple model incorporating renal function and diabetes
      mellitus.

PMID- 16949379
TI  - High-risk situations and procedures.
AB  - With the wider use of imaging and interventional techniques that require the use
      of iodinated contrast media in seriously ill patients, many clinical situations
      occur where patients may be at increased risk for contrast-induced nephropathy
      (CIN). There is little guidance for clinicians in these areas. The aim of this
      review is to assess the available literature. Acute renal failure is a common
      complication following coronary artery bypass surgery, and exposure to contrast
      medium may increase the risk for this condition, although there is insufficient
      evidence to make a definitive statement. Evidence is also limited for patients
      with liver disease: in those undergoing transarterial chemoembolization,
      cirrhosis may be a risk factor for renal failure. There is some evidence that
      periprocedural hypotension may be a risk factor for CIN after percutaneous
      coronary intervention, but no published information was identified on the
      significance of shock or hypotension in other groups of patients. The published
      evidence on the risk of CIN in renal transplant recipients is inconsistent. In
      emergency situations, the course of action is usually dictated by clinical
      circumstances; the renal status of a patient is likely to be unknown and it is
      important to ensure adequate volume expansion, especially after the procedure. In
      all clinical situations that are potentially associated with a high risk for CIN,
      the decision to administer contrast medium is a matter for clinical judgment,
      based on the clinical status of the patient and the expected benefits of the
      investigation or procedure.

PMID- 16949380
TI  - Contrast medium use.
AB  - Various properties of iodinated contrast media (osmolality, ionic versus
      nonionic, and viscosity) may contribute to contrast-induced nephropathy (CIN).
      Therefore, the choice of contrast medium affects the risk for CIN. There is good
      evidence that low-osmolar contrast media are less nephrotoxic than high-osmolar
      contrast media in patients at increased risk for CIN who receive intra-arterial
      iodinated contrast. Current evidence suggests that nonionic isosmolar contrast
      presents the lowest risk for CIN in patients with chronic kidney disease (CKD),
      particularly in those patients with diabetes mellitus. Intra-arterial
      administration of contrast media may be associated with a greater risk for CIN
      above that observed with intravenous administration. The use of gadolinium or
      CO(2) as alternative contrast media to avoid the risk of nephrotoxicity cannot be
      substantiated by clinical trials and therefore cannot be recommended. Most
      studies show that, within a class, higher volumes (>100 mL) of iodinated contrast
      medium are associated with a higher risk for CIN. However, in patients at high
      risk, such as those with CKD and diabetes, even small volumes of contrast medium
      can have adverse effects on renal function.

PMID- 16949381
TI  - Strategies to reduce the risk of contrast-induced nephropathy.
AB  - In view of the clinical importance of contrast-induced nephropathy (CIN),
      numerous potential risk-reduction strategies have been evaluated. Adequate
      intravenous volume expansion with isotonic crystalloid (1.0-1.5 mL/kg per hr) for
      3-12 hours before the procedure and continued for 6-24 hours afterward can lessen
      the probability of CIN in patients at risk. There are insufficient data on oral
      fluids (as opposed to intravenous volume expansion) as a CIN-prevention strategy.
      No adjunctive medical or mechanical treatment has been proved to be efficacious
      in reducing risk for CIN. Prophylactic hemodialysis and hemofiltration have not
      been validated as effective strategies. The CIN Consensus Working Panel
      considered that, of the pharmacologic agents that have been evaluated,
      theophylline, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
      (statins), ascorbic acid, and prostaglandin E(1) deserve further evaluation. N
      acetylcysteine is not consistently effective in reducing the risk for CIN.
      Fenoldopam, dopamine, calcium channel blockers, atrial natriuretic peptide, and l
      arginine have not been shown to be effective. Use of furosemide, mannitol, or an
      endothelin receptor antagonist is potentially detrimental. Nephrotoxic drugs
      should be withdrawn before contrast administration in patients at risk for CIN.

PMID- 16949383
TI  - Sex steroid hormone pathway genes and health-related measures in women of 4
      races/ethnicities: the Study of Women's Health Across the Nation (SWAN).
AB  - We synthesized findings relating health outcomes and genetic variants of the sex
      steroid hormone pathway in women from the Study of Women's Health Across the
      Nation (SWAN) Genetics Study. The SWAN Genetics Study, a component of the
      longitudinal SWAN study, describes selected genetics characteristics of health
      related attributes during the menopausal transition in African American,
      Caucasian, Chinese, and Japanese women. At baseline, SWAN recruited menstruating
      women aged 42 to 52 years, who were not using exogenous hormones. Immortalized
      cell lines were developed and genotyped in 1,538 specimens from 1,757
      participants in the genetics study. Genotypes and haplotypes from 6 genes (27
      single nucleotide polymorphisms [SNPs]) in the sex steroid hormone pathway were
      related to circulating hormone concentrations, menstrual cycle profiles, and
      health-related outcomes, including lipids, diabetes mellitus, depressive
      symptoms, measures of cognition, bone mineral density (BMD), and vasomotor
      symptoms. Allele frequencies and distances differed substantially in the 4
      race/ethnicity-specific groups evaluated, leading to variable patterns of
      association with health-related measures. For example, 17HSD genotypes were
      highly associated with diabetes risk in Caucasian women, whereas its haplotypes
      were associated with diabetes risk in both African American and Caucasian women.
      Several SNPs were associated with multiple outcomes. ESR1 rs3798577 was
      significantly associated with circulating estradiol concentrations, indicators of
      ovarian aging, high-density lipoprotein (HDL) cholesterol, apolipoprotein A-1,
      insulin sensitivity, and lumbar spine BMD. CYP1A1 rs2606345 was related to
      estrogen metabolite concentrations, vasomotor symptoms, and depressive symptoms.
      Some associations were much more prominent in specific races/ethnicities; Chinese
      women had statistically significant relations between ESR2 rs1256030 and HDL
      cholesterol, lumbar spine BMD, hip BMD, and metabolic syndrome. Importantly,
      women in the SWAN Genetics Study were typical of women in the community-based
      SWAN sample. This community-based sample of women from the SWAN Genetics Study
      identified important genetic sex steroid hormone pathway variants in relation to
      measures of health status. The magnitude and breadth of these relationships
      should motivate further research to verify and extend the findings.

PMID- 16949384
TI  - Endogenous estradiol and its association with estrogen receptor gene
      polymorphisms.
AB  - We evaluated potential associations between single nucleotide polymorphism (SNP)
      variants of the estrogen receptor genes ESR1 and ESR2 and circulating estradiol
      (E2) concentrations in women of 4 races/ethnicities. The study population was
      drawn from participants in the Study of Women's Health Across the Nation (SWAN).
      A total of 1,538 African American, Caucasian, Chinese, and Japanese women from
      SWAN participated in the Sex Steroid Hormone Genetics Protocol by providing blood
      for sex steroid hormone analyses and consenting to lymphocyte transformation from
      which DNA was extracted and genotyped. We evaluated 4 ESR1 SNPs (ESR1 rs9340799,
      ESR1 rs2234693, ESR1 rs728524, and ESR1 rs3798577), and 3 ESR2 SNPs (ESR2
      rs1255998, ESR2 rs1256030, and ESR2 rs1256065). Mean E2 level was 196.0 +/- 4.0
      pmol/L in women who were premenopausal and perimenopausal (with blood drawn on
      days 2 through 5 of the menstrual cycle follicular phase); however, mean E2
      levels in Chinese and Japanese women were lower (155.7 +/- 10.6 pmol/L and 170.0
      +/- 10.3 pmol/L, respectively) than in African American (196.4 +/- 8.1 pmol/L, P
      <0.05) or Caucasian women (210.7 +/- 5.9 pmol/L, P <0.002). The ESR1 rs3798577 CC
      genotype was associated with lower circulating E2 concentrations in African
      American women (P <0.07) and explained about 1% of the variation in circulating
      E2 concentrations. In Japanese women, the GC genotype of ESR2 rs1255998 was
      associated with significantly lower circulating E2 concentrations that explained
      about 4% of the variation. Circulating E2 concentrations were not strongly or
      consistently associated with selected polymorphisms for the estrogen receptor
      genes. The 2 strongest associations explained <4% of the total variation in the
      circulating E2 concentrations.

PMID- 16949385
TI  - Aromatase gene (CYP 19) polymorphisms and endogenous androgen concentrations in a
      multiracial/multiethnic, multisite study of women at midlife.
AB  - A limited number of studies have focused on androgens in women's health,
      particularly at the genetic level. We evaluated testosterone and estradiol (E2)
      levels among women in relation to 5 single nucleotide polymorphisms (SNPs) of the
      aromatase (CYP 19) gene, the cytochrome P450 enzyme that converts androgens to
      estrogens. We related 5 aromatase SNPs (CYP 19 rs2414096, CYP 19 rs936306, CYP 19
      rs2446405, CYP 19 rs1008805, and CYP 19 rs749292) to serum androgen and E2
      markers in 1,538 participants of the Study of Women's Health Across the Nation
      (SWAN), including 412 African American, 807 Caucasian, 151 Chinese, and 168
      Japanese women. Aromatase allele and genotype frequencies differed significantly
      among racial/ethnic groups. Compared with other genotypes of the CYP 19 rs936306
      polymorphism, the TT genotype was associated with a significant difference in the
      testosterone to E2 (T:E2) ratio--lower testosterone and higher E2 levels-
      especially in African American women. Japanese women with the AA genotype of the
      CYP 19 rs749292 polymorphism had lower testosterone and E2 levels but higher
      levels of sex hormone-binding globulin (SHBG) compared with Japanese women with
      the AG and GG genotypes. Among Caucasian women, there was markedly lower SHBG
      levels among those with the AA genotype of the CYP 19 rs2414096 polymorphism
      compared with other genotypes, after adjusting for age and body mass index. Three
      of 5 aromatase gene SNPs were associated with variation in serum androgen
      concentrations among women, both within and between racial/ethnic groups.
      Aromatase genetic markers may be important in understanding the emerging
      associations reported between endogenous androgens and women's health status.

PMID- 16949386
TI  - Characterizing variation in sex steroid hormone pathway genes in women of 4
      races/ethnicities: the Study of Women's Health Across the Nation (SWAN).
AB  - This report characterizes genotypes and haplotypes in 6 genes (27 single
      nucleotide polymorphisms [SNPs]) from the Sex Steroid Hormone Genetics Protocol
      developed though the DNA Repository of the Study of Women's Health Across the
      Nation (SWAN) Genetics Study. The SWAN Genetics Study is a component of a
      longitudinal study describing health-related attributes of the menopausal
      transition in African American, Caucasian, Chinese, Hispanic, and Japanese women.
      At baseline, SWAN recruited menstruating women, aged 42 to 52 years, who were not
      using exogenous hormones. During the sixth and seventh years of the study, buccal
      cells in a mouthwash slurry and whole blood were collected for a DNA repository.
      Immortalized cell lines were created and genotyped in 1,538 specimens from 1,757
      women who participated in the SWAN Genetics Study. DNA from those cells was
      genotyped for genes in the sex steroid hormone pathway. SNPs were evaluated for
      genotype and allele frequencies (and differences) according to race/ethnicity and
      haplotyped in anticipation of studying their associations with health-related
      measures. We demonstrated that allele frequencies differed significantly by
      race/ethnicity. There was substantial linkage disequilibrium among many of the
      SNPs and only a few SNPs showed significant Hardy-Weinberg disequilibrium within
      race/ethnicity. Finally, there are a number of haplotype patterns that vary
      according to race/ethnicity, including a "yin-yang" pattern for 17HSD among
      Caucasian, Chinese, and Japanese women, but not among African American women.
      Repository specimens developed in anticipation of genomic or metabolomics studies
      can extend the contribution of the parent study by developing hybrid strategies
      that support both SNP association studies as well as coarse and fine mapping to
      evaluate possible genomic locations of causal variants.

PMID- 16949387
TI  - Menstrual cycle markers of ovarian aging and sex steroid hormone genotypes.
AB  - We related variation in 4 sex steroid genes to 3 phenotypic indicators of ovarian
      aging, including no evidence of luteal activity as a marker of anovulatory
      cycles, shorter or longer menstrual cycle lengths, and the profiles of
      metabolites of estrogens, progesterone, follicle-stimulating hormone, and
      luteinizing hormone measured in urine samples collected daily across a menstrual
      cycle in women aged 43 to 53 years. The study sample included 485 menstruating
      women without hormone therapy who had collected daily urine hormone samples
      across 1 menstrual cycle or 50 days, whichever occurred first. There were 14
      single nucleotide polymorphisms from 4 genes, including estrogen receptor-alpha
      (ESR1), estrogen receptor-beta, aromatase, and 17beta hydroxysteroid
      dehydrogenase type 1, related to ovarian aging phenotypes that include the
      presence or absence of luteal activity, menstrual cycle lengths < or > 24 to 31
      days, and profiles of urinary hormone metabolites. Women with the TT genotype of
      ESR1 rs3798577 have evidence of advanced ovarian aging compared with women with
      the CT or CC genotypes, after adjustment for race/ethnicity, chronologic age, and
      race/ethnicity-specific body mass index. Further, women with the TC and CC
      genotypes of ESR1 rs2234693 may have a greater likelihood of more advanced
      ovarian aging than do women with the TT genotype, adjusting for covariates. Using
      a candidate gene approach, 2 ESR1 polymorphisms are related to 3 phenotypic
      markers of ovarian aging, suggesting a possible role for the ESR1 gene in the
      timing of the menopausal transition.

PMID- 16949388
TI  - CYP1A1 and CYP1B1 polymorphisms and their association with estradiol and estrogen
      metabolites in women who are premenopausal and perimenopausal.
AB  - The purpose of this study was to relate measured concentrations of estradiol (E2)
      and the urinary estrogen metabolites 2-hydroxyestrone (2-OHE1) and 16alpha
      hydroxyestrone (16alpha-OHE1) to single nucleotide polymorphisms (SNPs) from
      CYP1A1 and CYP1B1, the primary genes involved in estrogen catabolism. We
      investigated the association of 4 CYP1A1 SNPs (CYP1A1 rs4646903, CYP1A1
      rs1531163, CYP1A1 rs2606345, and CYP1A1 rs1048943) and 2 CYP1B1 SNPs (CYP1B1
      rs162555 and CYP1B1 rs1056836) to circulating serum E2 concentrations and the
      urinary estrogen metabolites 2-OHE1 and 16alpha-OHE1. The associations were
      evaluated in 1,340 participants of 4 racial/ethnic groups from the Study of
      Women's Health Across the Nation (SWAN) who were premenopausal and
      perimenopausal. There was substantial variation in the allele frequencies of the
      SNPs for African American and Caucasian women. There was, however, remarkable
      comparability between Chinese and Japanese women; their CYP1A1 and CYP1B1 allele
      frequencies differed by only < or =11%. There was significant variation in E2
      concentrations by genotype within racial/ethnic group for CYP1A1 rs2606345. In
      particular, Japanese women with the CC genotype had lower E2 concentrations than
      did Japanese women with the AC genotype. Chinese women with the CC genotype had
      higher 2-OHE1 concentrations than did Chinese women with the AC genotype.
      Further, African American women with the CC genotype had higher 16alpha-OHE1
      concentrations than did those with other genotypes. CYP1A1 rs2606345 may play an
      important role in estrogen metabolism in women who are premenopausal and
      perimenopausal.

PMID- 16949389
TI  - Vasomotor symptom prevalence is associated with polymorphisms in sex steroid
      metabolizing enzymes and receptors.
AB  - The relation of single nucleotide polymorphisms (SNPs) of genes involved in
      estrogen function to vasomotor symptoms (VMS) has been inadequately explored. We
      evaluated SNPs in sex steroid-metabolizing genes and estrogen receptors (ERs) for
      their association with VMS (hot flashes, night sweats, and/or cold sweats)
      reported by women who were premenopausal or in early perimenopause at baseline.
      The study population was drawn from participants in the Study of Women's Health
      Across the Nation (SWAN). African American, Caucasian, Chinese, and Japanese
      women, 42 to 52 years of age at baseline, who were enrolled in the longitudinal,
      community-based cohort of SWAN provided questionnaire, interview, weight and
      height measurements, and serum samples through the sixth annual visit. SNPs
      associated with the sex steroid hormone pathway were genotyped and available for
      1,538 participants. These SNPs were associated with reporting VMS > or =6 days
      compared with <6 days in the past 2 weeks using race/ethnicity-specific repeated
      measures logistic regression models. Participants were on average 46 years old at
      baseline. The prevalence of VMS reporting increased in all racial/ethnic groups
      from baseline to the sixth annual follow-up visit. After adjustment for
      covariates, several SNPs encoding genes responsible for estrogen metabolism and
      ERs were associated with decreased odds of reporting VMS, including the CYP1B1
      rs1056836 GC genotype in African American women; 17HSD rs615942 TG, 17HSD
      rs592389 TG, and 17HSD rs2830 AG genotypes in Caucasian women; and the CYP1A1
      rs2606345 AC genotype in Chinese women. We identified race/ethnicity-specific
      associations between VMS reporting and specific polymorphisms for sex steroid
      metabolizing enzymes and sex steroid receptors. Clarification of the mechanisms
      of the associations and confirmation in other populations is warranted.

PMID- 16949390
TI  - Sex steroid hormone polymorphisms, high-density lipoprotein cholesterol, and
      apolipoprotein A-1 from the Study of Women's Health Across the Nation (SWAN).
AB  - We evaluated potential associations between single nucleotide polymorphism (SNP)
      variants in estrogen receptor (ERalpha and ERbeta) genes, high-density
      lipoprotein (HDL) cholesterol, and apolipoprotein A-1 (apoA-1) concentrations in
      women of 4 races/ethnicities. Participants included 1,520 African American,
      Caucasian, Chinese, and Japanese women from the Study of Women's Health Across
      the Nation (SWAN) who were premenopausal or perimenopausal and who were also
      enrolled in the SWAN Genetics Study, which collected blood for lipid analyses and
      carried out lymphocyte transformation from which DNA was extracted and genotyped.
      We evaluated SNPs from ERalpha and ERbeta genes (ESR1 and ESR2, respectively),
      including ESR1 rs9340799, ESR1 rs2234693, ESR1 rs728524, ESR1 rs3798577, ESR2
      rs1255998, ESR2 rs1256065, and ESR2 rs1256030. The mean HDL cholesterol and apoA
      1 values for these women were 1.47 mmol/L and 1.51 g/L, respectively. Japanese
      women with the ESR1 rs3798577 TC genotype had significantly lower apoA-1 (P=0.02)
      and HDL cholesterol levels (P=0.03) than did those with the TT genotype. African
      American women with the ESR1 rs728524 GG genotype had higher HDL cholesterol
      levels than did women with the AA or AG genotypes (P=0.05). ESR2 rs1256030 and
      ESR2 rs1256065 genotypes were associated with HDL cholesterol concentrations in
      Chinese women (P=0.05). Although associations were identified between the ESR1
      and ESR2 SNP variants and lipids in these women, these associations were not
      consistently observed across the 4 racial/ethnic groups, nor were the
      associations consistently inclusive of both HDL cholesterol and apoA-1. These
      genetic variants provide limited evidence of associations with lipids that may
      help explain the cardioprotective effect of premenopausal status in women.

PMID- 16949391
TI  - The association of genetic polymorphisms in sex hormone biosynthesis and action
      with insulin sensitivity and diabetes mellitus in women at midlife.
AB  - We evaluated associations of insulin sensitivity, metabolic syndrome, and
      diabetes mellitus with single nucleotide polymorphism (SNP) variants from sex
      hormone biosynthesis and action in women of 4 races/ethnicities. DNA was
      extracted from transformed cell samples of 1,538 women in the Study of Women's
      Health Across the Nation (SWAN). African American, Caucasian, Chinese, and
      Japanese women in SWAN enrolled in the Sex Steroid Hormone Genetics Protocol from
      whom fasting glucose and insulin measures (for estimating insulin sensitivity),
      diabetes status, and metabolic syndrome classification were obtained. SNPs from
      the genes encoding aromatase (CYP 19), 17beta-hydroxysteroid dehydrogenase
      (17HSD) type 1, and the estrogen receptors-alpha (ESR1) and -beta (ESR2) were
      measured. The prevalence of metabolic syndrome was 20% in Chinese women, 22% in
      Japanese women, 28% in Caucasian women, and 43% in African American women. The
      prevalence of diabetes was 3% in Chinese women, 4% in Japanese women, 7% in
      Caucasian women, and 19% in African American women. Significant associations of
      CYP 19 genotypes and insulin sensitivity were observed in African American,
      Caucasian, and Japanese women. Selected ESR1 and ESR2 genotypes were associated
      with insulin sensitivity and metabolic syndrome only in Japanese and Chinese
      women. The strongest associations related 17HSD genotypes to diabetes in
      Caucasian women, with odds ratios ranging from 4.4 to 7.5 and confidence
      intervals that excluded the null value. We observed strong associations between
      variations in sex hormone biosynthesis and function genes with insulin
      sensitivity, the metabolic syndrome, and diabetes that varied by race/ethnicity.
      The strong association of 17HSD and diabetes in Caucasian women has not been
      previously reported and should be further investigated.

PMID- 16949392
TI  - The association of bone mineral density with estrogen receptor gene
      polymorphisms.
AB  - The purpose of this investigation was to evaluate single nucleotide polymorphism
      (SNP) variants of the estrogen receptor genes ESR1 and ESR2 and bone mineral
      density (BMD) of the lumbar spine (LS-BMD) or total hip (hip BMD) in women of 4
      races/ethnicities who were premenopausal or in early perimenopause. The sample
      consisted of 1,301 participants from the Study of Women's Health Across the
      Nation (SWAN) with measures of BMD and genotyping; of these, 295 were African
      American, 693 were Caucasian, 151 were Chinese, and 162 were Japanese. We
      evaluated the potential association of LS-BMD or hip BMD with 4 SNPs from the
      ESR1 gene (ESR1 rs9340799, ESR1 rs2234693, ESR1 rs728524, and ESR1 rs3798577),
      and 3 SNPs from the ESR2 gene (ESR2 rs1255998, ESR2 rs1256030, and ESR2
      rs1256065). Unadjusted mean LS-BMD values ranged from 1.141+/-0.14 g/cm(2) in
      African American women to 1.031+/-0.11 g/cm2 in Japanese women; unadjusted mean
      hip BMD values ranged from 1.053+/-0.14 g/cm2 in African American women to
      0.862+/-0.10 g/cm2 in Chinese women. African American and Japanese women with the
      ESR1 rs2234693 (PvuII) CC genotype had higher LS-BMDs than did their peers with
      the TT genotype (P=0.009 and P=0.04, respectively). Japanese women with the ESR1
      rs3798577 CC or TC genotypes had lower LS-BMD than did Japanese women with the TT
      genotype (P=0.02 and P=0.01, respectively). Caucasian women with the TC genotype
      for ESR2 rs1256030 had lower LS-BMDs than did those with the CC genotype
      (P=0.02). Chinese women who were heterozygous for ESR2 rs1256030 or ESR2
      rs1256065 had significantly higher LS-BMDs and hip BMDs than did the referent
      groups for each of these SNPs (CC and AA, respectively). Associations between BMD
      and ESR1 and ESR2 genotypes varied by race/ethnicity and by bone site. Our
      results differ from those previously reported for 2 ESR1 genotypes (ESR1
      rs2234693 [PvuII] and ESR1 rs9340799 [XbaI]). Moreover, 2 ESR1 and 3 ESR2 SNPs we
      studied have not previously been examined with respect to BMD. Among these, ESR2
      rs1256030 and ESR2 rs1256065 appear to have an effect at both the lumbar spine
      and hip in Chinese women and may warrant further study.

PMID- 16949393
TI  - Sex steroid hormone gene polymorphisms and depressive symptoms in women at
      midlife.
AB  - Single nucleotide polymorphism (SNP) genotype frequencies were examined to
      determine whether variation in 6 estrogen-related genes was associated with
      differences in self-reported depressive symptoms in women. In this substudy of
      the Study of Women's Health Across the Nation (SWAN), DNA from a
      multiracial/multiethnic sample of 1,538 African American, Caucasian, Chinese, and
      Japanese women aged 42 to 52 years participating in SWAN was genotyped.
      Depressive symptoms were measured with the Center for Epidemiologic Studies
      Depression (CES-D) scale. After excluding data from women taking antidepressants
      (n=103), statistical models were fit using multivariate logistic regression to
      predict the association of estrogen-related polymorphisms with the dichotomized
      CES-D score. Among Caucasian women, those with the CYP1A1 rs2606345 CC and AC
      genotypes had approximately 2-fold greater odds of having depressive symptoms
      than did those with the AA genotype (95% confidence intervals [CIs], 1.33 to 4.66
      and 1.25 to 3.14, respectively). African American women with the CC genotype of
      the same SNP had 10-fold greater odds of having more depressive symptoms than did
      women with the AA genotype (95% CI, 1.20 to 86.20). In Japanese women, the odds
      of depressive symptoms were nearly 5-fold higher among those with CYP 19 rs936306
      TT genotype (95% CI, 1.10 to 22.17) than in women with the CC genotype and 9.6
      fold higher (95% CI, 2.01 to 45.81) than in women with the CT genotype. The odds
      of depressive symptoms among Chinese women with the 17HSD rs615942 TT genotype
      were nearly 11-fold higher than in those with the GT genotype (95% CI, 1.94 to
      60.84) and >7-fold higher than in those with the GG genotype (95% CI, 1.13 to
      51.82). These data provide evidence that selected genes involved in estrogen
      synthesis and metabolism increase the odds of more depressive symptoms in women
      who are premenopausal or perimenopausal.

PMID- 16949394
TI  - Cognitive functioning and sex steroid hormone gene polymorphisms in women at
      midlife.
AB  - Single nucleotide polymorphism (SNP) genotype frequencies were examined to
      determine whether variation in 6 estrogen-related genes was associated with
      differences in cognitive functioning in women at midlife. DNA from a
      multiracial/multiethnic sample of 875 African American, Caucasian, Chinese, and
      Japanese women aged 45 to 56 years participating in the Study of Women's Health
      Across the Nation (SWAN) was genotyped. Gene markers from the sex steroid hormone
      pathway were linked to measures of cognitive functioning including the Digit Span
      Backward Test (DSB), a measure of working memory; the Symbol Digit Modalities
      Test (SDMT), a measure of perceptual speed; and the East Boston Memory Test
      (EBMT), a measure of episodic memory. Statistical models were fit using logistic
      regression and general linear models to estimate the strength of association of
      estrogen-related polymorphisms with DSB, SDMT, and EBMT scores. On the EBMT,
      African American women and Caucasian women with ESR1 rs9340799 GG genotypes had
      about 1.5 to 2.0 times greater odds of remembering story elements on the EBMT
      immediate recall test. Caucasian women with ESR1 rs2234693 CC genotypes had 1.3
      to 1.5 times greater odds of remembering story elements on the EBMT-delayed
      recall test. Chinese women with 17HSD rs615942 GG genotypes, 17HSD rs592389 TT
      genotypes, and 17HSD rs2830 GG genotypes had about 1.7 times greater odds of
      remembering story elements on the EBMT-immediate recall test. African American
      women with CYP 19 rs936306 CC genotypes had about 0.25 to 0.40 lower odds of
      remembering story elements on the EBMT-immediate recall test, whereas Chinese
      women with CYP 19 rs936306 CC genotypes had about 2.3 times greater odds of
      remembering story elements on both the EBMT-immediate and -delayed recall tests.
      On the DSB, African American women with CYP 19 rs749292 GG genotype had a higher
      mean score. On the SDMT, Japanese women with ESR1 rs728524 GG genotypes had a
      higher mean score. On the 3 tests of cognitive functioning, there was 1
      significant finding for CYP1A1 and none for the CYP1B1 or ESR2 SNPs. We conclude
      that selected genes involved in estrogen synthesis and metabolism may be
      associated with performance differences on cognitive function tests. Also, the
      relevant estrogen-related polymorphisms may vary by race/ethnicity.

PMID- 16949395
TI  - Recurrence of spontaneous versus medically indicated preterm birth.
AB  - OBJECTIVE: Despite the increased tendency of preterm birth to recur, little is
      known with regard to recurrence risks for spontaneous and medically indicated
      preterm birth as well as recurrence risks in relation to severity of preterm
      birth. We examined the recurrence of spontaneous and medically indicated preterm
      birth. STUDY DESIGN: A population-based, retrospective cohort study of births in
      Missouri (1989 to 1997) was carried out with analyses restricted to women who
      delivered their first 2 consecutive singleton live births (n = 154,809). Women
      who experienced spontaneous onset of labor and subsequently delivered preterm
      (less than 35 weeks) were classified as spontaneous preterm birth. Medically
      indicated preterm birth included women who delivered preterm through a labor
      induction or a prelabor cesarean delivery. Risk and odds ratio of preterm birth
      recurrence were derived from fitting multivariate conditional logistic regression
      models after adjusting for potential confounders. RESULTS: If the first pregnancy
      resulted in a spontaneous preterm birth, then affected women were more likely to
      deliver preterm spontaneously (adjusted odds ratio 3.6, 95% confidence interval
      3.2, 4.0) and also as a medically indicated preterm birth (odds ratio 2.5, 95%
      confidence interval 2.1, 3.0) in the second birth. Similarly, if the first
      pregnancy resulted in a medically indicated preterm birth, affected women were
      10.6-fold (95% confidence interval 10.1, 12.4) more likely to deliver preterm
      because of medical indications in the second pregnancy as well as preterm
      spontaneously (odds ratio 1.6, 95% confidence interval 1.3, 2.1). The greatest
      risk of recurrence of preterm birth in the second pregnancy tended to occur
      around the same gestational age as preterm birth in the first pregnancy,
      regardless of the clinical subtype. CONCLUSION: The observation that spontaneous
      preterm birth is not only associated with increased recurrence of spontaneous but
      also medically indicated preterm birth and vice versa, suggests that the 2
      clinical subtypes may share common etiologies.

PMID- 16949396
TI  - Shoulder dystocia: the unpreventable obstetric emergency with empiric management
      guidelines.
AB  - OBJECTIVE: Much of our understanding and knowledge of shoulder dystocia has been
      blurred by inconsistent and scientific studies that are of limited scientific
      quality. In an evidence-based format, we sought to answer the following
      questions: (1) Is shoulder dystocia predictable? (2) Can shoulder dystocia be
      prevented? (3) When shoulder dystocia does occur, what maneuvers should be
      performed? and (4) What are the sequelae of shoulder dystocia? STUDY DESIGN:
      Electronic databases, including PUBMED and the Cochrane Database, were searched
      using the key word "shoulder dystocia." We also performed a manual review of
      articles included in the bibliographies of these selected articles to further
      define articles for review. Only those articles published in the English language
      were eligible for inclusion. RESULTS: There is a significantly increased risk of
      shoulder dystocia as birth weight linearly increases. From a prospective point of
      view, however, prepregnancy and antepartum risk factors have exceedingly poor
      predictive value for the prediction of shoulder dystocia. Late pregnancy
      ultrasound likewise displays low sensitivity, decreasing accuracy with increasing
      birth weight, and an overall tendency to overestimate the birth weight. Induction
      of labor for suspected fetal macrosomia has not been shown to alter the incidence
      of shoulder dystocia among nondiabetic patients. The concept of prophylactic
      cesarean delivery as a means to prevent shoulder dystocia and therefore avoid
      brachial plexus injury has not been supported by either clinical or theoretic
      data. Although many maneuvers have been described for the successful alleviation
      of shoulder dystocia, there have been no randomized controlled trials or
      laboratory experiments that have directly compared these techniques. Despite the
      introduction of ancillary obstetric maneuvers, such as McRoberts maneuver and a
      generalized trend towards the avoidance of fundal pressure, it has been shown
      that the rate of shoulder-dystocia associated brachial plexus palsy has not
      decreased. The simple occurrence of a shoulder dystocia event before any
      iatrogenic intervention may be associated with brachial plexus injury.
      CONCLUSION: For many years, long-standing opinions based solely on empiric
      reasoning have dictated our understanding of the detailed aspects of shoulder
      dystocia prevention and management. Despite its infrequent occurrence, all
      healthcare providers attending pregnancies must be prepared to handle vaginal
      deliveries complicated by shoulder dystocia.

PMID- 16949397
TI  - Intensive care in obstetrics: an evidence-based review.

PMID- 16949398
TI  - Preeclampsia and subsequent risk of cancer in Utah.
AB  - OBJECTIVE: The purpose of this study was to determine if preeclampsia is
      associated with a reduced risk of cancer later in life. STUDY DESIGN: We
      performed a cohort study where women with preeclampsia over the interval 1947 to
      1999 were identified from the Utah Population Database. Preeclamptics (n =
      17,432) were matched 1:3 with nonpreeclamptics (n = 52,296) on maternal age and
      birth year. Pregnancy, demographic, and cancer information was extracted from
      subjects and their offspring in linked datasets. Relative risk and hazard ratios
      were calculated. RESULTS: In a matched analysis using univariable random-effects
      Poisson regression, preeclampsia was protective against the development of cancer
      later in life (RR 0.91, 95% CI 0.84-0.99 with P = .027). In a multivariable
      clustered Cox regression model with the end point of cancer later in life,
      preeclampsia was associated with a lower risk of cancer (HR 0.92, 95% CI 0.85
      0.99 with P = .039). These findings were supported by stratified and competing
      risk analyses. CONCLUSION: Women whose pregnancies were affected by preeclampsia
      have a decreased risk of developing cancer.

PMID- 16949399
TI  - Induction of labor and cesarean delivery by gestational age.
AB  - OBJECTIVE: Studies of cesarean delivery (CD) rates among women undergoing
      induction of labor (IOL) often compare such women to women experiencing
      spontaneous labor at similar gestational ages. We sought to examine the
      association between IOL at various gestational ages and CD, accounting for the
      effect of increased gestational age among the comparison group who were managed
      expectantly. STUDY DESIGN: We conducted a retrospective cohort study of all term,
      singleton, cephalic presentation pregnancies delivered at our institution over 15
      years excluding cesarean deliveries before labor. For each gestational age of
      induction, we created a comparison group of women who were undelivered at that
      gestational age, and who experienced labor at some future gestational age.
      RESULTS: In women undergoing IOL at 38 weeks gestation, the CD rate was 11.9% as
      compared to 13.3% (P = .42) of women beyond 38 weeks gestation. The CD rate for
      induction of labor compared to ongoing pregnancy was 14.3% versus 15.0% (P = .62)
      at 39 weeks, 20.4% versus 19.0% (P = .41) at 40 weeks, and 24.3% versus 26.0% (P
      = .39) at 41 weeks. When controlling for potential confounding, there was a
      higher rate of CD among women with expectant management beyond 38 weeks (adjusted
      odds ratio [AOR] 1.80; 95% CI 1.29-2.53), 39 weeks (1.39; 95% CI 1.08-1.80), and
      40 weeks (AOR 1.27; 95% CI 1.00-1.62). CONCLUSION: Our findings suggest that IOL
      may not increase a woman's risk of CD when compared to expectant management.
      While this question has been addressed prospectively at 41 weeks gestation, it
      requires further examination at earlier gestations and among various subgroups.

PMID- 16949400
TI  - Fetuses with congenital heart disease demonstrate signs of decreased cerebral
      impedance.
AB  - OBJECTIVE: The purpose of this study was to determine whether fetuses with a
      congenital heart defect demonstrate changes in cerebrovascular impedance. STUDY
      DESIGN: Fetal echocardiograms from January 2001 to May 2005 were reviewed. Cases
      had sonographically diagnosed congenital heart defects; control subjects were
      gestational age-matched fetuses with normal echocardiograms. The pulsatility
      index in the middle cerebral artery was used to measure impedance to cerebral
      blood flow. Abnormal middle cerebral artery pulsatility index was defined as less
      than the 5th percentile. Cases were subgrouped into mixing versus nonmixing
      lesions. RESULTS: Of 142 total fetuses, there were significantly more abnormal
      middle cerebral artery pulsatility indices in the cases (5/71) than in the
      control subjects (0/71; P = .023); all abnormal middle cerebral artery
      pulsatility indices occurred in the fetuses with admixing cardiac lesions.
      CONCLUSION: Fetuses with congenital heart defect are significantly more likely to
      have decreased cerebrovascular impedance. This may represent a marker of cerebral
      hypoxemia that is due to intracardiac mixing of oxygenated and deoxygenated
      blood. Theoretically, this hypoxemia may contribute to the cause of abnormal
      neurologic development in these infants.

PMID- 16949401
TI  - Association of maternal fractures with adverse perinatal outcomes.
AB  - OBJECTIVE: We sought to assess the effects of fracture injuries on maternal and
      fetal/neonatal outcomes in a large obstetric population. STUDY DESIGN: We
      performed a retrospective cohort study using a database in which maternal and
      neonatal hospital discharge summaries were linked with birth and death
      certificates to identify any relation between maternal fractures and maternal and
      perinatal morbidity. Fracture injuries and perinatal outcomes were identified
      with the use of the International Classification of Diseases, 9th revision,
      Clinical Modification codes. Outcomes were further subdivided on the basis of
      anatomic site of fracture. RESULTS: A total of 3292 women with > or = 1 fractures
      were identified. Maternal mortality (odds ratio, 169 [95% CI, 83.2,346.4]) and
      morbidity (abruption and blood transfusion) rates were increased significantly in
      women who were delivered during hospitalization for their injury. Women who were
      discharged undelivered continued to have delayed morbidity, which included a 46%
      increased risk of low birth weight infants (odds ratio, 1.5 [95% CI, 1.3,1.7])
      and a 9-fold increased risk of thrombotic events (odds ratio, 9.2 [95% CI,
      1.3,65.7]) Pelvic fractures had the worst outcomes. CONCLUSION: Fractures during
      pregnancy are an important marker for poor perinatal outcomes.

PMID- 16949402
TI  - Skin autofluorescence, a marker of advanced glycation end products and oxidative
      stress, is increased in recently preeclamptic women.
AB  - OBJECTIVE: Advanced glycation end-products are considered to be markers of
      oxidative stress and to be involved in the atherosclerotic process. We
      investigated skin autofluorescence, which reflected advanced glycation end
      product accumulation, in recently preeclamptic women and its relationship with
      intima-media thickness, which is a marker of atherosclerosis. STUDY DESIGN: Skin
      autofluorescence of the arm and leg was measured in 26 preeclamptic women and 17
      control subjects at 3 to 13 months after delivery. Lipid profiles, smoking
      habits, and intima-media thickness of 5 carotid and femoral artery segments were
      recorded. RESULTS: The preeclampsia group was younger and had higher values for
      blood pressure, insulin resistance, common femoral artery intima-media thickness,
      and skin autofluorescence of the leg. With the use of linear regression analysis,
      the difference in leg autofluorescence was explained only by preeclampsia. In the
      preeclampsia group, skin autofluorescence of the leg correlated with smoking and
      common femoral artery intima-media thickness. CONCLUSION: These results support
      the hypothesis of accelerated atherosclerosis in recently preeclamptic women and
      the possible involvement of advanced glycation end-product accumulation.

PMID- 16949403
TI  - Outcomes of subsequent pregnancy after first pregnancy with early-onset
      preeclampsia.
AB  - OBJECTIVE: The aim of this study was to report outcome of subsequent pregnancy
      after early-onset preeclampsia in first pregnancy, and to evaluate potential risk
      factors for recurrence of preeclampsia and preterm delivery. STUDY DESIGN:
      Reproductive follow-up data were obtained for women with a history of early-onset
      preeclampsia, resulting in delivery before 34 weeks of gestation at the
      University Medical Center Utrecht, The Netherlands, between July 1993 and
      September 2002. The relative contributions of demographic data, outcome variables
      of first pregnancy, and common thrombophilias to the recurrence risk of
      preeclampsia and preterm delivery in subsequent pregnancy, were estimated by Cox
      proportional hazard models. RESULTS: Subsequent pregnancy outcome data were
      available for 120 women. Overall, preeclampsia reoccurred in the second pregnancy
      in 30 women (25%). However, 6 women delivered before 34 weeks of gestation (5%),
      20 women between 34 and 37 weeks of gestation (17%), and 94 women after 37 weeks
      of gestation (78%). Forty-one women (34%) had an uneventful pregnancy. Recurrence
      rates for preeclampsia or preterm delivery were not related to severity of first
      pregnancy complications, including delivery before 28 weeks of gestation,
      occurrence of hemolysis, elevated liver enzymes, and low platelet count syndrome,
      small-for-gestational age infants, and to hereditary or acquired thrombophilias.
      Chronic hypertension was related to a higher recurrence risk of preeclampsia in
      the second pregnancy (hazard ratio 2.1, 95% CI 1.0-4.4), and smoking was related
      to a higher recurrence risk of preterm birth (hazard ratio 2.4, 95% CI 1.1-5.6).
      CONCLUSION: Outcomes of subsequent pregnancy after first pregnancy with early
      onset preeclampsia is generally favorable.

PMID- 16949404
TI  - United States multicenter clinical usage study of the STAN 21 electronic fetal
      monitoring system.
AB  - OBJECTIVE: The fetal electrocardiogram system for electronic fetal monitoring
      (EFM) (STAN S21, Neoventa Medical, Moelndal, Sweden) has led to improved
      perinatal outcomes in other countries. We aimed to assess the ability of United
      States (US) obstetricians to use this system appropriately for intrapartum care.
      STUDY DESIGN: A prospective nonrandomized trial was conducted in 6 sites.
      Enrollment required a singleton vertex fetus, >36 weeks' gestation, with
      indications for direct fetal monitoring during first stage of labor. Appropriate
      use was measured by negative predictive value (NPV) of nonintervention for
      fetuses with nonreassuring fetal heart rate (FHR) patterns, normal STAN readings,
      and normal neonatal outcomes with umbilical cord arterial pH >7.12; and percent
      agreement (PA) for intervention decisions with 3 STAN experts who conducted
      retrospective case reviews blinded to outcome. RESULTS: Five hundred and thirty
      patients were enrolled. An NPV of 95.2% was achieved while PA between
      investigators and STAN experts was 84%, and 90%, for intervention and
      nonintervention, respectively. No fetus with metabolic acidosis requiring
      intervention was missed by US clinicians. CONCLUSION: US clinicians used the STAN
      system appropriately in a manner similar to that of experienced STAN users.

PMID- 16949405
TI  - The effect of maternal oxygen administration on fetal pulse oximetry during labor
      in fetuses with nonreassuring fetal heart rate patterns.
AB  - OBJECTIVE: Using fetal pulse oximetry, we sought to quantify the impact of
      maternal oxygen administration in the management of nonreassuring fetal heart
      rate patterns. STUDY DESIGN: In fetuses with specified abnormal nonreassuring
      fetal heart rate patterns, oxygen was administered to the mother, and fetal
      oxygenation was monitored with fetal pulse oximetry. After the fetal oxygen
      saturation on room air was recorded as a baseline, oxygen was administered to the
      mother for 30 minutes at 40% fraction of inspired oxygen and then 30 minutes at
      100% of inspired oxygen. The average fetal oxygen saturation during the last 15
      minutes of each period was calculated. Paired Student t test was used for
      comparison to baseline values. RESULTS: Compared with baseline values, a
      significant increase in fetal oxygen saturation was identified in women who
      received oxygen at 40% fraction of inspired oxygen (mean increase, 4.9%; P =
      .001) and at 100% of inspired oxygen (mean increase, 6.5%; P = .003). CONCLUSION:
      The administration of supplemental oxygen to laboring patients with nonreassuring
      fetal heart rate patterns increases fetal oxygen saturation substantially and
      significantly. Fetuses with the lowest initial oxygen saturations appear to
      increase the most.

PMID- 16949406
TI  - Cephalopelvic disproportion is associated with an altered uterine contraction
      shape in the active phase of labor.
AB  - OBJECTIVE: The purpose of this study was to determine if intrapartum contractions
      of a particular shape (rapid rise with slower return to baseline) are predictive
      of cephalopelvic disproportion (CPD). STUDY DESIGN: In an institutional review
      board (IRB)-approved study, cohorts of 100 women who underwent spontaneous
      vaginal delivery (SVD) and 100 who underwent cesarean section (C/S) for CPD or
      arrest of labor were consecutively identified between January 2004 and March
      2005. Inclusion criteria included term, singleton pregnancies, nulliparity, and
      absence of fetal anomalies. One hour of interpretable electronic fetal monitoring
      (EFM) was obtained in active labor. Fall to rise (F:R) ratio was calculated by
      measuring the time for a contraction to return to its baseline from its peak
      ("fall") and the time for a contraction to rise to its peak ("rise"). The F:Rs
      were then averaged over the number of contractions. Data were analyzed using
      Student t test, Chi-square, and Fisher exact tests where appropriate. RESULTS:
      Maternal demographics are listed in Table I. The average F:R ratio was 1.55 for
      SVD versus 1.77 for C/S, a statistically significant difference (P = .00003).
      Analysis of variance revealed this difference persists when controlled for the
      potentially confounding factors shown. At F:R >1.76, moreover, there was a trend
      towards larger birth weight (P = .06). CONCLUSION: Our study demonstrates there
      is a difference in uterine contraction configuration that is more common in those
      labors destined for C/S due to CPD. This may indicate the presence of a
      heretofore unknown feedback mechanism as the uterus adapts to the dysfunctional
      labor.

PMID- 16949407
TI  - Are there ethnic differences in the length of labor?
AB  - OBJECTIVE: The purpose of this study was to examine the lengths of the first and
      second stages of labor among different racial/ethnic groups to determine whether
      different norms should be established. STUDY DESIGN: This was a retrospective
      cohort study of all laboring, term, singleton, vertex deliveries in a single
      academic institution. Median lengths of first and second stages of labor were
      compared among 4 racial/ethnic groups: black, Asian, white, and Latina. Kruskal
      Wallis, Wilcoxon rank sum tests, and multivariate linear and logistic regression
      models were performed. RESULTS: In 27,521 births, the lengths of first stage of
      labor did not differ significantly among groups in the multivariate analysis. In
      the second stage of labor, black women had shorter labors, both overall and
      stratified by epidural use. In the multivariate analysis, when controlled for
      demographics, parity, epidural, chorioamnionitis, birthweight, delivery year, and
      labor management, black women had a shorter second stage than did white women
      (nulliparous women, 22 minutes; multiparous women, 7.5 minutes; P < .001) and
      lower rates of prolonged second stage (odds ratio, 0.6; P < .001). Nulliparous
      Asian women had a significantly longer second stage and higher rates of prolonged
      second stage, and nulliparous Latina women had a shorter second stage, compared
      with nulliparous white women. CONCLUSION: When data are controlled for
      confounding factors, black women had a shorter length of second stage of labor
      than did women in other ethnic groups. These differences appear to be clinically
      significant. This contributes to the support of a multifactorial redefinition of
      labor curves, which are used widely in the management of labor.

PMID- 16949408
TI  - Operative vaginal delivery and midline episiotomy: a bad combination for the
      perineum.
AB  - OBJECTIVE: The purpose of this study was to determine the impact of operative
      vaginal delivery (forceps or vacuum) and midline episiotomy on the risk of severe
      perineal trauma. STUDY DESIGN: In this retrospective cohort study, we assessed
      the impact of maternal and obstetric factors on the risk of development of severe
      perineal trauma (third- and fourth-degree perineal lacerations) for all
      singleton, vertex vaginal live births (n = 33,842) between 1996 and 2003.
      RESULTS: Among nulliparous women, 12.1% had operative vaginal delivery, 22.4% had
      midline episiotomy, and 8.1% experienced severe perineal trauma. Among
      multiparous women, 3.4% had operative vaginal delivery, 4.2% had midline
      episiotomy, and 1.2% experienced severe perineal trauma. Controlling for maternal
      age, ethnicity, birth weight and head circumference, evaluation of the
      interaction of episiotomy and delivery method revealed that forceps (nulliparous
      women: odds ratio [OR] 8.6, 95% CI 6.5-10.7; multiparous women: OR 26.3, 95% CI
      18.1-34.5) and episiotomy (nulliparous women: OR 4.5, 95% CI 3.7-5.4; multiparous
      women: OR 14.6, 95% CI 10.4-20.5) were consistently associated with the increased
      risk of anal sphincter trauma. In fact, the magnitude of effect of the
      statistically significant synergistic interaction was evidenced by more than 3
      fold excess of risk of using operative vaginal delivery alone. CONCLUSION: The
      use of operative vaginal delivery, particularly in combination with midline
      episiotomy, was associated with a significant increase in the risk of anal
      sphincter trauma in both primigravid and multigravid women. Given the reported
      substantial long-term adverse consequences for anal function, this combination of
      operative modalities should be avoided if possible.

PMID- 16949409
TI  - Risk factors for the breakdown of perineal laceration repair after vaginal
      delivery.
AB  - OBJECTIVE: The purpose of this study was to identify risk factors that are
      associated with the breakdown of perineal laceration repair in the postpartum
      period. STUDY DESIGN: We conducted a retrospective, case-control study to review
      perineal laceration repair breakdown in patients who were delivered between
      September 1995 and February 2005 at the University of Michigan. Bivariate
      analysis with chi-square test and t-test and stepwise logistic regression
      analysis were performed. RESULTS: Fifty-nine cases and 118 control deliveries
      were identified from a total of 14,124 vaginal deliveries. Risk factors were
      longer second stage of labor (142 vs 87 minutes; P = .001), operative vaginal
      delivery (odds ratio, 3.6; 95% CI, 1.8-7.3), mediolateral episiotomy (odds ratio,
      6.9; 95% CI, 2.6-18.7), third- or fourth-degree laceration (odds ratio, 3.1; 95%
      CI, 1.5-6.4), and meconium-stained amniotic fluid (odds ratio, 3.0; 95% CI, 1.1
      7.9). Previous vaginal delivery was protective (odds ratio, 0.38; 95% CI, 0.18
      0.84). Logistic regression showed the most significant factor to be an
      interaction between operative vaginal delivery and mediolateral episiotomy (odd
      ratio, 6.36; 95% CI, 2.18-18.57). CONCLUSION: The most significant events were
      mediolateral episiotomy, especially in conjunction with operative vaginal
      delivery, third- and fourth-degree lacerations, and meconium.

PMID- 16949410
TI  - Dystocia increases with advancing maternal age.
AB  - OBJECTIVE: The purpose of this study was to assess the influence of maternal age
      on obstetric indices of uterine efficiency in spontaneous nulliparous labor
      managed according to a standardized protocol in order to determine whether
      increasing maternal age is more commonly associated with dystocia. STUDY DESIGN:
      Information was collected prospectively and retrieved retrospectively from an
      obstetric database for a 5-year period on a consecutive series of nulliparas in
      spontaneous term (> or = 37 weeks' gestation) labor with singleton cephalic
      presentations. All women were managed according to an established Active
      Management protocol. Indices for dystocia, including need for oxytocin
      augmentation, prolonged labor (> 12 hr), instrumental delivery, and cesarean
      section were compared between 5 maternal age categories (< 20 years, 20-24, 25
      29, 30-34, and > or = 35 years). RESULTS: The obstetric outcomes of 10,737
      consecutive nulliparas in spontaneous term labor were analyzed for the 5 years
      1998 to 2002. The incidences of oxytocin augmentation, prolonged labor,
      instrumental delivery, and intrapartum cesarean section including cesareans for
      dystocia all increased significantly and progressively with increasing maternal
      age. Mean gestational age and birth weight were similar in each age category.
      CONCLUSION: In a context of uniform labor management, all 4 indices of dystocia
      examined were increased progressively with maternal age, although oxytocin
      augmentation proved a generally effective intervention in all age categories.
      These findings have implications for the analysis of intervention rates by health
      care providers, particularly in developed countries where the proportion of older
      nulliparas is increasing.

PMID- 16949411
TI  - Maternal age and the risk of stillbirth throughout pregnancy in the United
      States.
AB  - OBJECTIVE: The objective of the study was to examine the relationship of maternal
      age with stillbirth risk throughout gestation. STUDY DESIGN: A total of 5,458,735
      singleton gestations without reported congenital anomalies from the 2001 to 2002
      National Center for Health Statistics perinatal mortality and natality files were
      analyzed. Hazard rates (risk) of stillbirth (fetal death 20 weeks or longer) were
      calculated for each week of gestation. RESULTS: The risk of stillbirth at 37 to
      41 weeks for women 35 to 39 years old was 1 in 382 ongoing pregnancies and for
      women 40 years old or older, 1 in 267 ongoing pregnancies. Compared with women
      younger than 35 years old, the relative risk of stillbirth was 1.32 (95%
      confidence interval 1.22, 1.43) for women 35 to 39 years old and 1.88 (95%
      confidence interval 1.64, 2.16) for women 40 years old or older at 37 to 41
      weeks. This effect of maternal age persisted despite accounting for medical
      disease, parity, and race/ethnicity. CONCLUSION: Women who are of advanced
      maternal age are at higher risk of stillbirth throughout gestation; the peak risk
      period is 37 to 41 weeks.

PMID- 16949412
TI  - The transcriptome of the uterine cervix before and after spontaneous term
      parturition.
AB  - OBJECTIVE: This study was designed to identify genes differentially expressed in
      the human uterine cervix after spontaneous term labor. STUDY DESIGN: The
      transcriptome of cervical tissue was characterized using Affymetrix HG-U133 plus
      2 microarrays. Samples were collected from patients at term not in labor (n = 7)
      and after spontaneous labor (n = 9). Microarray statistical analysis included
      robust multiarray average, reduction of invariant probes, and permutation
      analysis for differential expression. Real-time quantitative reverse
      transcriptase-polymerase chain reaction assays of selected genes were performed
      on a new set of samples from term patients without labor (n = 10) and patients
      after spontaneous labor (n = 9). RESULTS: (1) The cervical transcriptome of term
      patients without labor was dramatically different from that of patients who
      underwent labor; (2) unique genes (n = 1192) were differentially expressed in the
      cervical tissue from patients after spontaneous labor, compared with that of the
      term patients without labor (false discovery rate less than 0.05, absolute fold
      change greater than 2); (3) Gene Ontology analysis indicated that multiple
      "Biological Process" categories were enriched, including "response to biotic
      stimulus," "apoptosis," "epidermis development," and "steroid metabolism"; (4) of
      major interest, genes involved in neutrophil chemotaxis were dramatically up
      regulated in specimens from women after spontaneous labor; (5) real-time
      quantitative reverse transcriptase-polymerase chain reaction confirmed the
      increased expression of interleukin-8, interleukin-6, and vascular endothelial
      growth factor in patients after spontaneous labor; and (6) Toll-like receptor-3
      and Toll-like receptor-5 showed decreased gene expression in patients after
      spontaneous labor. This was confirmed by real-time quantitative reverse
      transcriptase-polymerase chain reaction. CONCLUSION: (1) Cervical dilatation in
      term labor is associated with a stereotypic gene expression pattern determined by
      microarray, which is characterized by overexpression of genes involved in
      neutrophil chemotaxis, apoptosis, extracellular matrix regulation, and steroid
      metabolism; (2) Toll-like receptor-3 and Toll-like receptor-5 are differentially
      regulated during spontaneous parturition at term; and (3) this study provides an
      unbiased and comprehensive description of the changes in the cervical
      transcriptome before and after spontaneous term labor.

PMID- 16949413
TI  - Risk factors for cervical insufficiency after term delivery.
AB  - OBJECTIVE: Cervical insufficiency can be unexpected in a woman with a previous
      term birth. Our objective was to determine what risk factors, if any, place women
      with a term delivery at risk for cervical insufficiency in a subsequent
      pregnancy. STUDY DESIGN: Demographic characteristics were collected for a cohort
      of women with at least 1 previous term birth followed by cervical insufficiency
      (subject group) and for uncomplicated multiparous women (control group).
      Multiparous women with cervical insufficiency (subjects; n = 49) were compared
      with multiparous women who were experiencing repeat term birth with no history of
      cervical insufficiency (control group; n = 49). RESULTS: Patients with cervical
      insufficiency were similar to control subjects demographically. No difference was
      noted in previous cervical procedures or spontaneous preterm deliveries.
      Multivariate logistic regression analysis identified a history of curettage (odds
      ratio, 4.6; 95% CI, 1.7-12.5), precipitous delivery (odds ratio, 6.8; 95% CI, 1.6
      29.6), and prolonged second stage of labor (odds ratio, 24.9; 95% CI, 2.4-253) as
      independent predictors of cervical insufficiency. CONCLUSION: Multiparous women
      who experience cervical insufficiency after a term birth are more likely to have
      had a previous precipitous delivery, a prolonged second stage of labor, or a
      previous curettage compared with multiparous women who experience a repeat term
      birth with no cervical insufficiency.

PMID- 16949414
TI  - Placental inflammation and viral infection are implicated in second trimester
      pregnancy loss.
AB  - OBJECTIVE: Second trimester pregnancy loss continues to be a poorly understood
      adverse obstetric outcome. A case control study was performed to determine if:
      (1) similar to early spontaneous preterm birth, second trimester loss is
      associated with histologic chorioamnionitis (HCA); and (2) if HCA is present,
      which organisms may mediate this placental inflammation. STUDY DESIGN: Cases were
      patients with a spontaneous second trimester loss. Controls were patients who
      presented for induction of labor for fetal or maternal indications. Nested
      polymerase chain reaction (PCR) was performed on placental tissues to detect the
      presence of viruses and pathogenic and atypical bacteria. Chi-square and Fisher
      exact test were used to determine if HCA and/or the presence of virus or bacteria
      were significantly associated with second trimester loss. The associations of
      interest were adjusted for possible confounders using multivariable logistic
      regression. RESULTS: HCA was more prevalent in cases (67%) than controls (16%) (P
      < .001). Seventy-nine percent (66/84) of cases and 44% (7/16) of controls were
      positive for any virus (P = .01). The rate of bacterial infection was similar in
      both cases and controls (P = .35). In multivariable logistic regression models,
      HCA (odds ratio [OR] 14.58, 2.62-81.15) and the presence of any virus (OR 6.62,
      1.56-28.07) were independently associated with second trimester loss. CONCLUSION:
      These studies demonstrate that spontaneous second trimester loss is strongly
      associated with HCA and viral infections.

PMID- 16949415
TI  - The Alabama Preterm Birth study: polymorphonuclear and mononuclear cell placental
      infiltrations, other markers of inflammation, and outcomes in 23- to 32-week
      preterm newborn infants.
AB  - OBJECTIVE: The purpose of this study was to better understand the relationship
      between placental polymorphonuclear and mononuclear cell infiltrations with
      bacterial cultures, markers of inflammation, and preterm outcomes. STUDY DESIGN:
      This was a prospective study in 446 women who were delivered of a singleton
      infant at <32 weeks of gestational age. Five placental sites were categorized as
      having polymorphonuclear or mononuclear infiltrations. Results were compared with
      placental and cord cultures, umbilical cord interleukin-6 levels, and neonatal
      outcomes. RESULTS: Polymorphonuclear, but not mononuclear, cell infiltrations
      were more common at the earliest gestational ages and in black women (56.0% vs
      39.3%; P < .01). Polymorphonuclear infiltration was associated with spontaneous
      preterm birth (73.9% vs 8.0%; P < .0001), but not with preeclampsia (9.9% vs 34%;
      P < .0001). Women with positive cultures, high interleukin-6 levels, and clinical
      chorioamnionitis all had significantly more polymorphonuclear infiltrations than
      did women without those conditions (all probability values, <.0001). In all
      sites, polymorphonuclear infiltration was associated with neonatal systemic
      inflammatory response syndrome (P < .0001) and in the cord with necrotizing
      enterocolitis (22.4% vs 13.5%; P = .02). Intraventricular hemorrhage and neonatal
      death were not associated with polymorphonuclear infiltration. Polymorphonuclear
      infiltration at all sites was associated with less respiratory distress syndrome
      (P < .01). Mononuclear cell infiltration, when present in the decidua basalis,
      was associated with an increase in neonatal intraventricular hemorrhage (23.8% vs
      7.4%; P < .0004). Plasmacytic infiltrates were associated with increased
      intraventricular hemorrhage (29.4% vs 8.3%; P = .01) and neonatal death (27.8% vs
      9.2%; P = .02). CONCLUSION: Polymorphonuclear infiltrations of the free
      membranes, chorionic plate, and umbilical cord were associated with positive
      intrauterine cultures and elevated cord blood interleukin-6. There was also an
      association with systemic inflammatory response syndrome and necrotizing
      enterocolitis, but not with intraventricular hemorrhage or death, and with
      decreased respiratory distress syndrome. Decidual mononuclear cell infiltration
      was associated with an increased risk of intraventricular hemorrhage and decidual
      plasma cell infiltration with increased intraventricular hemorrhage and neonatal
      death.

PMID- 16949416
TI  - Short cervix on ultrasound: does indomethacin prevent preterm birth?
AB  - OBJECTIVE: Our aim was to estimate if indomethacin therapy prevents preterm birth
      (PTB) in women with a short cervical length (CL) on transvaginal ultrasound
      (TVU). STUDY DESIGN: Individual-level data from all randomized trials including
      asymptomatic women with a short CL on TVU were analyzed for use of indomethacin
      at the time of the short CL. The trials eligible would be ones that randomized
      women with a short CL <25 mm, identified between 14 and 27 weeks. The eligible
      trials randomized such women to receive either cerclage or no cerclage. Only
      women who did NOT receive cerclage were analyzed. Exclusion criteria were major
      fetal anomaly and cerclage. We compared demographics, risk factors, and outcomes
      in women who, at the time of the short CL, received indomethacin or not. Primary
      outcome was PTB <35 weeks. RESULTS: Three of the 4 randomized trials identified
      had databases which recorded indomethacin use at the time of the short CL. A
      total of 139 women with a short CL <25 mm identified at 14 to 27 weeks were
      identified. Of these women, 99 (71.2%) received indomethacin, and 40 (28.8%) did
      not. Demographics and risk factors, including previous PTB (45.5% vs 62.5%; P =
      .11), were similar in the 2 groups. The primary outcome of PTB <35 weeks occurred
      in 29.3% (29/99) of women who received indomethacin, and 42.5% (17/40) of women
      who did not receive indomethacin (RR 0.69, 95% CI 0.44-1.13). PTB <24 weeks
      occurred in 1.0% (1/99) versus 7.5% (3/40), respectively (RR 0.14; 95% CI 0.02
      0.92). Incidence of perinatal death was similar in the 2 groups (6% vs 10%; RR
      0.61, 95% CI 0.19-1.95). CONCLUSION: Indomethacin therapy for asymptomatic women
      who have a short CL <25 mm on TVU at 14 to 27 weeks and do not receive a cerclage
      did not prevent spontaneous PTB <35 weeks, but did prevent PTB <24 weeks. Further
      research including larger numbers and a randomized trial design is necessary to
      further clarify the effectiveness as well as the risks of this therapy.

PMID- 16949417
TI  - Are in vitro fertilization pregnancies with early spontaneous reduction high
      risk?
AB  - OBJECTIVE: The objective of the study was to determine whether spontaneous
      reduction in in vitro fertilization pregnancies results in outcomes comparable
      with in vitro fertilization singleton pregnancies or ongoing twin pregnancies.
      STUDY DESIGN: Women with in vitro fertilization pregnancies from 2003 to 2005 who
      had first-trimester ultrasound and delivered in our hospital were identified.
      Those with documented reduction from dichorionic twins to a single viable fetus
      at 14 weeks or less were categorized as spontaneous reduction pregnancies and
      were compared with dichorionic twin and singleton pregnancies without reduction.
      RESULTS: One hundred sixty-eight singleton, 55 spontaneous reduction, and 86 twin
      pregnancies were included. Gestational age at delivery was similar in the
      singleton and spontaneous reduction groups; twins delivered significantly
      earlier. Spontaneous reduction was associated with lower birth weight than other
      singleton pregnancies (median 3062 g versus 3425 g; P = .005). The rate of pre
      eclampsia was higher in pregnancies with spontaneous reduction, compared with
      other singleton pregnancies 9.3% versus 2.4%; P = .04). CONCLUSION: Spontaneous
      reduction of a twin to a singleton pregnancy is associated with prolonged
      gestation and higher birth weight for the remaining fetus.

PMID- 16949418
TI  - Impact of weight loss between pregnancies on recurrent preterm birth.
AB  - OBJECTIVE: Low maternal pre-pregnancy body-mass index (BMI) has been associated
      with preterm birth (PTB). Women delivering preterm are at increased for recurrent
      PTB. Our goal was to determine whether change in BMI between pregnancies alters
      the risk of PTB. STUDY DESIGN: From our electronic perinatal database, we
      identified women who delivered consecutive pregnancies at our institution. Women
      were grouped by prepregnancy BMI category (underweight: <18.5, normal: 18.5-24.9,
      overweight: 25-29.9, obese: >30 kg/m2). They were then grouped based on change in
      actual BMI ("increase": >5 kg/m2, "stable": within 5 kg/m2, "decrease": >5 kg/m2)
      and change in BMI category between pregnancies. The risk of PTB was correlated to
      change in BMI. P < .05 was considered significant. RESULTS: One thousand two
      hundred forty-one women met inclusion criteria. Women with a PTB in their first
      pregnancy had more PTB in their second than those with a term birth in their
      first pregnancy (33.6% vs 8.0%, P < .001). Women whose BMI decreased more than 5
      kg/m2 had more frequent PTB in the second pregnancy than those who did not (21.1%
      vs 9.3%, P = .01). For those with a term birth in the first pregnancy, PTB in the
      second did not increase with declining BMI. However, for women with a PTB in the
      first pregnancy, PTB was more frequent in the second if their BMI decreased a BMI
      category (53.8% vs 27.6%, P = .05) or if BMI decreased more than 5 kg/m2 (80.0%
      vs 28.2%, P = .01). CONCLUSION: Women whose BMI declines between pregnancies are
      at increased risk for PTB, particularly if they delivered a prior preterm
      gestation.

PMID- 16949419
TI  - Uterine transcriptomes of bacteria-induced and ovariectomy-induced preterm labor
      in mice are characterized by differential expression of arachidonate metabolism
      genes.
AB  - OBJECTIVE: The purpose of this study was to identify changes in gene expression
      that are associated with preterm labor induced by either bacteria or ovariectomy.
      STUDY DESIGN: Pregnant mice (14.5 days of gestation) were allocated to: (1)
      intrauterine injection of heat-inactivated Escherichia coli; (2) media alone; (3)
      ovariectomy; or (4) sham operation. The uterine transcriptome was studied with
      photolithographic, very short oligonucleotide-based microarrays, and arachidonate
      metabolism genes were assayed with quantitative reverse transcriptase-polymerase
      chain reaction. Significance was determined by analysis of variance. RESULTS:
      Microarray-based gene expression changes in the arachidonate metabolism pathway
      are associated globally with bacteria-induced preterm labor (P < or = .0031) and
      ovariectomy-induced preterm labor (P < or = .00036). Quantitative real-time
      reverse transcriptase-polymerase chain reaction measurements demonstrated that
      bacteria-induced preterm labor substantially increased the expression of genes
      involved in prostaglandin synthesis. In contrast, ovariectomy-induced preterm
      labor increased the expression of genes involved in lipoxin, leukotriene, and
      hydroxyeicosatetraenoic acid synthesis. CONCLUSION: Bacteria-induced and
      ovariectomy-induced preterm labor each express a different balance of genes that
      are required for the synthesis of prostaglandins, lipoxins, leukotrienes, and
      hydroxyeicosatetraenoic acids.

PMID- 16949420
TI  - Fetal macrophages are not present in the myometrium of women with labor at term.
AB  - OBJECTIVE: The basic mechanisms responsible for human parturition remain to be
      elucidated. The influx of fetal leukocytes into the myometrium has been recently
      proposed to be a crucial event in the onset of murine parturition. Surfactant
      protein-A has been implicated in the initiation of labor. In mice, it is thought
      that surfactant protein-A induces migration and subsequent activation of amniotic
      fluid macrophages of fetal origin, which then invades the myometrium. The present
      study was conducted to determine whether fetal macrophages invade the myometrium
      of women in labor. STUDY DESIGN: Placental bed biopsy specimens were obtained
      from patients in labor who delivered male neonates at term (n = 7). Myometrial
      sections of postpartum hysterectomy specimens obtained from women who delivered
      of male neonates (n = 3) were also analyzed. Formalin-fixed, paraffin-embedded
      sections were immunostained for CD68 or CD14 (which are markers for macrophages);
      immunoreactive myometrial macrophages were specifically procured by laser capture
      microdissection. Sex typing was done by polymerase chain reaction for the
      amelogenin gene with genomic DNA that was isolated from the macrophages.
      Chromogenic in situ hybridization with a Y chromosome-specific probe was also
      performed on paraffin-embedded histologic sections. RESULTS: Amelogenin
      allelotypes of the macrophages were consistent with female alleles in all cases
      that were tested, indicating a maternal origin. Chromogenic in situ hybridization
      demonstrated the absence of Y chromosome-positive mononuclear cells in the
      myometrium in all cases. CONCLUSION: These observations, from a limited number of
      cases, suggest that migration of fetal macrophages from the amniotic cavity or
      the chorioamniotic membranes into the myometrium does not occur during human
      labor. The trafficking of fetal macrophages in labor seems to be different in
      humans and mice.

PMID- 16949421
TI  - Perinatal outcomes among Asian American and Pacific Islander women.
AB  - OBJECTIVE: The purpose of this study was to examine perinatal outcomes between
      Asian American and Pacific Islander subgroups. STUDY DESIGN: This is a
      retrospective study of all Asian American/Pacific Islander women who were
      delivered at Stanford University Medical Center from 1998 to 2003. Asian American
      women were subdivided into the following groups: Indian/Pakistani, Chinese,
      Filipino, Japanese, Korean, Pacific Islanders (individuals from Tonga, Samoa,
      Guam, or Polynesia), and Vietnamese. Perinatal outcomes included gestational
      hypertension/preeclampsia, gestational diabetes mellitus, preterm delivery,
      cesarean delivery, birthweight <2500 g, and birthweight >4000 g. RESULTS: In the
      study population of 3779 Asian American women, there were statistically
      significant differences (P < .01) between most of the outcomes that were
      examined. Filipina women had the highest risk of gestational
      hypertension/preeclampsia (adjusted odds ratio, 2.21); Indian/Pakistani women had
      the highest risk of preterm delivery (adjusted odds ratio, 1.67), gestational
      diabetes mellitus (adjusted odds ratio, 1.39), and low birthweight at term
      (adjusted odds ratio, 2.30); and Pacific Islander women had the highest risk of
      macrosomia (adjusted odds ratio, 3.67). CONCLUSION: Significant differences in
      perinatal outcomes exist between subgroups of the Asian American and Pacific
      Islander community. Future research on race/ethnicity and perinatal outcomes
      should examine heterogeneity among these groups before collapsing these
      individual subgroups into the larger group "Asian." Individuals should be
      counseled regarding perinatal risk according to their specific Asian subgroup.

PMID- 16949422
TI  - Gestational age at abortion: the impact of first-trimester risk assessment for
      aneuploidy.
AB  - OBJECTIVE: The purpose of this study was to determine the impact of first
      trimester risk assessment on gestational age at abortion for abnormal fetal
      karyotype. STUDY DESIGN: Women who had abortion for trisomies 21, 18, and 13,
      45X, and Triploidy in our hospital from 1999 to 2005 were included. Data
      collected included gestational age at abortion, method of prenatal diagnosis, and
      whether or not first-trimester risk assessment was performed. Analysis was
      performed using Spearman Correlation, Chi-square for trend, Fisher exact test,
      and Mann-Whitney U test. RESULTS: One hundred forty-nine patients were included.
      There was an inverse correlation between year of abortion and gestational age
      (rho = -0.31; P < .001) coinciding with significant increases in the rates of
      first-trimester risk assessment and prenatal diagnosis by chronic villus
      sampling. CONCLUSION: First-trimester risk assessment is associated with earlier
      diagnosis of aneuploidy. In our institution, this has led to earlier abortions.
      Availability of quality first-trimester risk assessment can decrease the need for
      abortion later in pregnancy.

PMID- 16949423
TI  - Is there a nuchal translucency millimeter measurement above which there is no
      added benefit from first trimester serum screening?
AB  - OBJECTIVE: The purpose of this study was to evaluate whether there is a nuchal
      translucency (NT) measurement, independent of gestational age, above which
      immediate diagnostic testing should be offered without waiting for first
      trimester serum markers. STUDY DESIGN: Thirty-six thousand one hundred twenty
      patients had successful measurement of simple NT at 10 3/7 to 13 6/7 weeks and
      had first trimester serum screening. No risks were reported until second
      trimester serum screening was completed. RESULTS: Thirty-two patients (0.09%) had
      NT > or = 4.0 mm; the lowest combined first trimester trisomy 21 risk assessment
      in euploid cases was 1 in 8 and among aneuploidy cases was 7 in 8. One hundred
      twenty-eight patients (0.3%) had simple NT > or = 3.0 mm: the lowest combined
      first trimester trisomy 21 risk assessment of any patient in this group was 1 in
      1479 and the lowest risk assessment among aneuploid cases was 1 in 2. Ten
      patients (8%) had first trimester trisomy 21 risk assessments lowered to less
      that 1:200 and none of these 10 cases had an abnormal outcome. CONCLUSION: During
      first trimester Down syndrome screening, whenever an NT measurement of 3.0 mm or
      greater is obtained there is minimal benefit in waiting for serum screening
      results, and no benefit for NT of 4.0 mm or greater. Differentiation between
      cystic hygroma and enlarged simple NT (> or = 3.0 mm) is now a moot point as both
      are sufficiently high risk situations to warrant immediate CVS.

PMID- 16949424
TI  - Amniotic fluid index and birth weight: is there a relationship in diabetics with
      poor glycemic control?
AB  - OBJECTIVE: This study was undertaken to evaluate if the previously demonstrated
      relationship between macrosomia (> 4000 g) and polyhydramnios (> 25 cm) is linear
      across birth weights (BW) in diabetic patients with poor glycemic control. STUDY
      DESIGN: Using a prospectively collected database of patients undergoing
      amniocentesis for fetal lung maturity for various indications with amniotic fluid
      index (AFI) obtained < or = 7 days before delivery and BWs available (n = 69), we
      computed gestational age (GA) specific AFI and BW centiles using standard tables.
      BW and AFI centiles were analyzed in diabetic patients with poor glycemic control
      using linear regression and ANOVA, with P < .05 significant. RESULTS: In the
      poorly controlled diabetic population, a linear relationship existed between AFI
      and BW centiles, with the largest BW centiles having the highest AFI centiles (P
      < .0001). CONCLUSION: The previously noted relationship between elevated AFI and
      BW centiles in the general patient population is linear in diabetic patients with
      poor glycemic control.

PMID- 16949425
TI  - Obstetric outcomes in overweight and obese adolescents.
AB  - OBJECTIVE: Obese adult pregnant women have increased rates of maternal and
      neonatal complications. Our objective was to examine adverse obstetric outcomes
      in overweight adolescent women. STUDY DESIGN: In a retrospective case-control
      study of 4822 women who were < 19 years old, 3324 appropriate-weight subjects
      (body mass index, 18.5-24.9 kg/m2) and 1498 overweight subjects (body mass index,
      > or = 25 kg/m2) were compared. Frequencies and odds ratios for adverse maternal
      or neonatal events were computed. RESULTS: Compared with appropriate-weight
      adolescents, primary cesarean delivery (odds ratio, 1.6; 95% CI, 1.4-1.9),
      failure to progress/cephalopelvic disproportion (odds ratio 1.6; 95% CI, 1.3
      1.9), labor induction (odds ratio, 1.4; 95% CI, 1.3-1.7), pregnancy-induced
      hypertension (odds ratio, 1.8; 95% CI, 1.4-2.3), preeclampsia (odds ratio, 1.7;
      95% CI, 1.2-2.4), and gestational diabetes mellitus (odds ratio, 3.0, 95% CI, 1.6
      5.4) were significantly more common in overweight adolescents. Significant
      neonatal findings included an increased incidence of macrosomia (odds ratio, 1.6;
      95% CI, 1.2-2.0) and a decreased incidence of low birth weight infants (odds
      ratio, 0.6; 95% CI, 0.4-0.8) and small for gestational age infants (odds ratio,
      0.8; 95% CI, 0.7-1.0). CONCLUSION: Overweight adolescent women are at increased
      risk for adverse neonatal and perinatal outcomes. With rates of overweight
      increasing overall, overweight in the gravid adolescent is a pressing perinatal
      and public health concern.

PMID- 16949426
TI  - The relationship of fetal position and ethnicity with shoulder dystocia and birth
      injury.
AB  - OBJECTIVE: The objective of this study was to examine factors associated with the
      occurrence of shoulder dystocia and subsequent perinatal outcomes. STUDY DESIGN:
      We conducted a retrospective cohort study of 29,612 consecutive term, singleton,
      vertex vaginal deliveries. The primary outcome was reported shoulder dystocia.
      Fetal position, ethnicity, and their interaction terms were examined along with
      maternal characteristics, induction and length of labor, operative vaginal
      delivery, epidural, and birth weight in both bivariate and multivariate analyses.
      RESULTS: Among women who met study criteria, 524 (1.8%) experienced a shoulder
      dystocia. African American women had the highest risk of shoulder dystocia
      (2.6%), compared with other races/ethnicities (P = .001). Women who delivered in
      occiput posterior position were noted to have a lower risk for shoulder dystocia
      (1.1%) as compared with occiput anterior position (1.8%, P = .046). However, in
      the setting of a shoulder dystocia, a higher risk of brachial plexus injury was
      observed in neonates delivered in occiput posterior position (adjusted odds ratio
      10.4, 95% confidence interval 3.03 to 35.88) by vacuum-assisted vaginal delivery
      (adjusted odds ratio 3.24, 95% confidence interval 1.37 to 7.67) and neonates
      weighing 4000 g or more (adjusted odds ratio 2.53, 95% confidence interval 1.09
      to 5.85). CONCLUSION: Overall African American women have an increased risk of
      shoulder dystocia, but their neonates are not more likely to experience birth
      injury. Although occiput posterior position has a protective effect for shoulder
      dystocia, the risk of brachial plexus injury is increased in the setting of a
      persistent occiput posterior delivery. These factors should be used to consider a
      patient's prospective risk for shoulder dystocia and associated outcomes.

PMID- 16949427
TI  - Antenatal sonographic prediction of twin chorionicity.
AB  - OBJECTIVE: We sought to determine the accuracy of antenatal diagnosis of twin
      chorionicity at a single tertiary care center and assess the consequences of
      incorrect diagnoses. STUDY DESIGN: Twins with chorionicity diagnosed by
      ultrasound < or = 24 weeks' gestation were retrospectively reviewed. Chorionicity
      was assigned by sonographic findings including placental location(s), the lambda
      and T-signs, and/or fetal gender(s). Postnatal diagnosis was determined by
      placental histopathologic examination. Medical records of antenatal-postnatal
      discordant chorionicities were reviewed for adverse sequelae. RESULTS:
      Chorionicity was correctly assigned antenatally in 392/410 (95.6%) twins. The
      sensitivity, specificity, and positive and negative predictive values of
      monochorionicity assessed < or = 14 weeks were 89.8%, 99.5%, 97.8%, and 97.5%.
      Corresponding statistical values for the second trimester were 88.0%, 94.7%,
      88.0%, and 94.7%. Two cases of inaccurate antenatal diagnoses affected patient
      counseling or were associated with adverse clinical outcomes. CONCLUSION:
      Antenatal assessment of chorionicity is accurate; however, incorrect diagnoses do
      occur and can affect reliable patient counseling and management.

PMID- 16949428
TI  - Are the Agency for Healthcare Research and Quality obstetric trauma indicators
      valid measures of hospital safety?
AB  - OBJECTIVE: The objective of the study was to examine whether the United States
      Agency for Health Care Research and Quality obstetric patient safety indicators
      are significantly affected by patient-specific and hospital-level characteristics
      not related to the safety environment. STUDY DESIGN: Administrative data for all
      nonfederal Illinois hospitals in 2001 were used to analyze the association of a
      hospital's obstetric trauma rates with patient and hospital-level factors.
      Multivariable random effects logistic regression analyses was used to account for
      hospital-level clustering. RESULTS: A total of 175,374 deliveries from 142
      Illinois hospitals were available for analysis. The frequency of obstetric trauma
      was significantly associated with multiple patient-specific and hospital-level
      factors. Specifically, for any vaginal delivery, premature delivery, multiple
      gestation, excessive fetal growth, and prolonged pregnancy was associated with
      obstetric trauma risk. For spontaneous delivery, a prior cesarean was associated
      with trauma risk as well. Maternal age was associated with trauma risk at
      cesarean as well as at vaginal delivery. With regard to hospital-level factors, a
      higher annual delivery volume and a higher cesarean rate were associated with
      increased risk of trauma with either type of vaginal delivery, whereas in the
      intensity with which hospitals coded their medical records was associated with
      trauma risk for all routes of delivery. CONCLUSION: The risk of obstetric trauma
      is significantly influenced by both patient and hospital characteristics and is
      not a good indicator of patient safety.

PMID- 16949429
TI  - Discrepancies in pelvic anatomy.

PMID- 16949430
TI  - Timing of prophylactic antibiotic administration in the uninfected laboring
      gravida: a randomized clinical trial.

PMID- 16949432
TI  - Birth rate and its correlation with the lunar cycle and specific atmospheric
      conditions.

PMID- 16949435
TI  - TTTS amnioreduction versus septostomy.

PMID- 16949437
TI  - Allen-Masters syndrome.

PMID- 16949439
TI  - Silver enhancement of quantum dots resulting from (1) metabolism of toxic metals
      in animals and humans, (2) in vivo, in vitro and immersion created zinc
      sulphur/zinc-selenium nanocrystals, (3) metal ions liberated from metal implants
      and particles.
AB  - Autometallographic (AMG) silver enhancement is a potent histochemical tool for
      tracing a variety of metal containing nanocrystals, e.g. pure gold and silver
      nanoclusters and quantum dots of silver, mercury, bismuth or zinc, with sulphur
      and/or selenium. These nanocrystals can be created in many different ways, e.g.
      (1) by manufacturing colloidal gold or silver particles, (2) by treating an
      organism in vivo with sulphide or selenide ions, (3) as the result of a metabolic
      decomposition of bismuth-, mercury- or silver-containing macromolecules in cell
      organelles, or (4) as the end product of histochemical processing of tissue
      sections. Such nano-sized AMG nanocrystals can then be silver-amplified several
      times of magnitude by being exposed to an AMG developer, i.e. a normal
      photographic developer enriched with silver ions. The present monograph attempts
      to provide a review of the autometallographic silver amplification techniques
      known today and their use in biology. After achieving a stronghold in
      histochemistry by Timm's introduction of the "silver-sulphide staining" in 1958,
      the AMG technique has evolved and expanded into several different areas of
      research, including immunocytochemistry, tracing of enzymes at LM and EM levels,
      blot staining, retrograde axonal tracing of zinc-enriched (ZEN) neurons,
      counterstaining of semithin sections, enhancement of histochemical reaction
      products, marking of phagocytotic cells, staining of myelin, tracing of gold ions
      released from gold implants, and visualization of capillaries. General technical
      comments, protocols for the current AMG methods and a summary of the most
      significant scientific results obtained by this wide variety of AMG histochemical
      approaches are included in the present article.

PMID- 16949440
TI  - How should results from clinical tests be integrated into the diagnostic process?

PMID- 16949441
TI  - Optical coherence tomography of retinal astrocytic hamartoma in 15 cases.
AB  - OBJECTIVE: To describe the features of retinal astrocytic hamartoma using optical
      coherence tomography (OCT). DESIGN: Retrospective, observational, noncomparative
      case series. PARTICIPANTS: Fifteen consecutive eyes from 14 patients with retinal
      astrocytic hamartoma. MAIN OUTCOME MEASURES: Optical coherence tomography
      characteristics of the tumor. RESULTS: The mean patient age at OCT was 33 years,
      and tuberous sclerosis was present in 3 patients (21%). By ophthalmoscopy, the
      mean basal diameter of the tumor was 3.6 mm. By OCT, the tumor showed
      hyperreflectivity at its surface, internal retinal disorganization, and a gradual
      gently sloping transition from a normal retina into a tumorous retina in all 15
      cases (100%). By OCT, the retinal disorganization was limited to the inner retina
      in 3 (20%), outer retina in 0 (0%), full retina in 5 (33%), and inner retina with
      no view of deeper layers due to shadowing in 7 (47%). On OCT, there was mild
      retinal traction on the surface of the tumor in 4 (27%), discrete internal moth
      eaten optically empty spaces representing intralesional calcification or
      intratumoral cavities in 10 (67%), and optical shadowing posterior to the tumor
      in 14 (93%). Other retinal findings on OCT included shallow elevation of the
      adjacent retina in 2 (13%), adjacent retinal edema in 4 (27%), and macular edema
      in 3 (20%). CONCLUSIONS: Retinal astrocytic hamartoma shows characteristic
      features on OCT, including a gradual transition from a normal retina into an
      optically hyperreflective mass with retinal disorganization, characteristic moth
      eaten spaces, and posterior shadowing.

PMID- 16949442
TI  - Causes of low vision and blindness in adult Latinos: the Los Angeles Latino Eye
      Study.
AB  - OBJECTIVE: To describe the causes of low vision and blindness in a population
      based sample of adult Latinos. DESIGN: Population-based cross-sectional study.
      PARTICIPANTS: Six thousand three hundred fifty-seven Latinos 40 years and older
      from 6 census tracts in Los Angeles, California. METHODS: Participants underwent
      a detailed ophthalmologic examination including measurement of best-corrected
      distance visual acuity using a standard Early Treatment for Diabetic Retinopathy
      Study protocol, a complete anterior and posterior segment evaluation by an
      ophthalmologist, Humphrey Visual field testing, and optic disc and fundus
      photography. Consensus diagnosis of independent investigators reviewing all
      patient data was used to determine the major causes of low vision and blindness
      in adult Latinos. MAIN OUTCOME MEASURES: Primary causes of vision loss in persons
      with low vision and blindness. RESULTS: The leading causes of low vision were
      cataract, diabetic retinopathy, and age-related macular degeneration, together
      accounting for approximately 82% of all persons with low vision. The primary
      causes of blindness were age-related macular degeneration, diabetic retinopathy,
      and myopic degeneration, accounting for 63% of the cases of blindness.
      CONCLUSIONS: Many of the leading causes of low vision and blindness in adult
      Latinos are potentially preventable and treatable diseases. Given the projected
      aging and growth in the Latino population, consideration needs to be given to the
      development of targeted early detection and treatment programs.

PMID- 16949443
TI  - Peripapillary retinal nerve fiber layer thickness in a population of 6-year-old
      children: findings by optical coherence tomography.
AB  - PURPOSE: To study the distribution of retinal nerve fiber layer (RNFL) thickness
      by ocular and demographic variables in a population-based study of young
      children. DESIGN: Population-based cross-sectional study. PARTICIPANTS: One
      thousand seven hundred sixty-five of 2238 (78.9%) eligible 6-year-old children
      participated in the Sydney Childhood Eye Study between 2003 and 2004. Mean age
      was 6.7 years (50.9% boys). METHODS: Detailed examination included cycloplegic
      autorefraction and measurement of axial length. Retinal nerve fiber layer scans
      using an optical coherence tomographer were performed with a circular scan
      pattern of 3.4-mm diameter. Multivariate analyses were performed to examine the
      distribution of RNFL parameters with gender, ethnicity, axial length, and
      refraction. MAIN OUTCOME MEASURES: Peripapillary RNFL thickness and
      RNFL(estimated integral) (RNFL(EI)), which measures the total cross-sectional
      area of ganglion cell axons converging onto the optic nerve head. RESULTS:
      Peripapillary RNFL thickness and RNFL(EI) were normally distributed. The mean+/
      standard deviation RNFL average thickness was 103.7+/-11.4 microm and RNFL(EI)
      was 1.05+/-0.12 mm2. Retinal nerve fiber layer thickness was least for the
      temporal quadrant (75.7+/-14.7 microm), followed by the nasal (81.7+/-19.6
      microm), inferior (127.8+/-20.5 microm), and superior (129.5+/-20.6 microm)
      quadrants. Multivariate adjusted RNFL average thickness was marginally greater in
      boys than in girls (104.7 microm vs. 103.2 microm; P = 0.007) and in East Asian
      than in white children (107.7 microm vs. 102.7 microm; P<0.0001). The RNFL was
      thinner with greater axial length (P(trend)<0.0001) and less positive spherical
      equivalent refractions (P(trend) = 0.004). CONCLUSIONS: Retinal nerve fiber layer
      average thickness and RNFL(EI) followed a normal distribution. Retinal nerve
      fiber layer thickness varied marginally with gender, but differences were more
      marked between white and East Asian children. Retinal nerve fiber layer thinning
      was associated with increasing axial length and less positive refractions.

PMID- 16949444
TI  - Combining structural and functional testing for detection of glaucoma.
AB  - PURPOSE: To assess whether the combined use of both structural and functional
      tests improves discrimination between healthy and glaucomatous eyes over either
      type of testing alone. DESIGN: Observational cross-sectional study. PARTICIPANTS:
      One hundred twenty-three eyes of 123 participants enrolled in the Diagnostic
      Innovations in Glaucoma Study. METHODS: Because both structural and functional
      tests were evaluated, 2 definitions of glaucoma were used: glaucomatous visual
      field (VF) damage based on repeatable abnormal standard automated perimetry
      results (n = 43) and glaucomatous optic disc (glaucomatous optic neuropathy
      [GON]) based on masked assessment of optic disc stereophotographs (n = 65).
      Participants had scanning laser polarimetry, optical coherence tomography (OCT),
      and confocal scanning laser ophthalmoscopy imaging in addition to frequency
      doubling technology (FDT) perimetry and short-wavelength automated perimetry
      (SWAP) testing completed within a 6-month interval. MAIN OUTCOME MEASURES: For
      each glaucoma definition, sensitivities and specificities were calculated for the
      best structural parameters, FDT perimetry pattern standard deviation (PSD), and
      SWAP PSD/glaucoma hemifield test, and then for each possible pairwise combination
      of one structural and one functional parameter. RESULTS: The best structural
      parameters for discriminating between glaucoma and control eyes were nerve fiber
      indicator for scanning laser polarimetry, inferior average retinal nerve fiber
      layer thickness for OCT, and Moorfields regression classification for confocal
      scanning laser ophthalmoscopy. Sensitivities and specificities for detecting
      glaucomatous VF damage for scanning laser polarimetry, OCT, confocal scanning
      laser ophthalmoscopy, FDT perimetry, and SWAP were 41.9% and 98.3%, 58.1% and
      98.3%, 58.1% and 84.5%, 44.2% and 98.3%, and 65.1% and 86.2%, respectively.
      Adding FDT perimetry to each of the best structural parameters led to a
      significant (P<0.05) increase in sensitivity without a significant change in
      specificity compared with structural parameters alone. Adding SWAP to each of the
      best structural parameters led to a significant increase in sensitivity and also
      a significant decrease in specificity compared with each structural parameter
      alone. CONCLUSIONS: A combination of parameters from structural tests and
      functional tests can improve the sensitivity of glaucoma detection. The
      sensitivity and specificity desired for a particular clinical application will
      determine the selection of the particular diagnostic tests.

PMID- 16949445
TI  - The association between glaucomatous visual fields and optic nerve head features
      in the Ocular Hypertension Treatment Study.
AB  - PURPOSE: To determine the association between change from baseline in the optic
      nerve head (ONH) and the visual field (VF) during follow-up of ocular
      hypertension participants in the Ocular Hypertension Treatment Study. DESIGN:
      Longitudinal randomized clinical trial. PARTICIPANTS: One hundred sixty-eight
      eyes of 152 ocular hypertensive participants ages 40 to 80 years. METHODS: Cox
      hazard models were applied to 3232 eyes, which included 81 eyes that reached a
      study end point by developing a glaucomatous VF (VF end point) and 128 eyes that
      reached a study end point by developing an optic disc change (optic disc end
      point). MAIN OUTCOME MEASURES: Primary open-angle glaucoma end point as
      determined by changes in the VF or optic disc. RESULTS: Forty-one eyes reached an
      end point by both VF and optic disc criteria; 40 eyes reached only a VF end
      point, and 87 reached only an optic disc end point. Times to reach isolated disc
      or field end points were similar. Visual field end points were more likely
      (P<0.0001) in eyes that showed the following ONH features: an ONH hemorrhage,
      thinning of the optic disc rim, or enlargement of the horizontal cup-to-disc
      (C/D) ratio. Optic disc end points were more likely (P<0.0001) in eyes that
      showed the following VF features: some evidence of a nasal step or a partial
      arcuate VF defect, or an increase in the pattern standard deviation (PSD).
      CONCLUSIONS: Both the VF and the optic disc must be monitored with equal
      diligence, because either may show the first evidence of glaucomatous damage.
      Changes in the ONH based on stereophotographic observation (rim thinning,
      hemorrhage, or a slight increase in C/D ratio) and VF changes (evidence of a
      nasal step/partial arcuate defect or an increase in PSD) suggest that these cases
      have an increased risk of developing glaucoma. Confirmation of such subtle
      findings should be sought through repeat testing and correlation with other
      clinical results.

PMID- 16949446
TI  - Risk factors for corneal ectasia after LASIK.
AB  - PURPOSE: To establish a grading system that helps identify high-risk individuals
      who may experience corneal ectasia after LASIK. DESIGN: Retrospective,
      comparative, interventional case series. PARTICIPANTS: One hundred forty-eight
      consecutive patients (148 eyes) were included in this study. Thirty-seven
      patients who underwent LASIK at other refractive centers experienced corneal
      ectasia in 1 eye after LASIK. One hundred eleven eyes of 111 patients who
      underwent successful LASIK during the same period were age and gender matched and
      served as controls. INTERVENTION: All patients underwent preoperative and
      postoperative topographic analysis of the cornea. The follow-up period in both
      groups of patients ranged from 2 to 5 years, with a mean follow-up of 3.6 years.
      All patients underwent LASIK for myopia (spherical equivalent, -4.00 to -8.00
      diopters). MAIN OUTCOME MEASURES: Corneal keratometry, oblique cylinder,
      pachymetry, posterior surface elevation, difference between the inferior and
      superior corneal diopteric power, and posterior best sphere fit (BSF) over
      anterior BSF were given a grade of 1 to 3 each. An ectasia grading system was
      established, and the cumulative risk score was assessed. RESULTS: Patients who
      had a grade of 7 or less showed no evidence of corneal ectasia, whereas 16 (59%)
      of 27 patients who had a grade of 8 to 12 had corneal ectasia. Twenty-one (100%)
      of 21 patients with a grade of more than 12 had corneal ectasia after LASIK
      (P<0.0001). CONCLUSIONS: A risk score may help in the prediction of patients who
      are at risk of experiencing corneal ectasia after LASIK. A prospective clinical
      study is needed to assess the validity of these risk factors.

PMID- 16949447
TI  - Comparison of Pentacam and Orbscan IIz on posterior curvature topography
      measurements in keratoconus eyes.
AB  - PURPOSE: To compare the measurements of posterior elevation above the best-fit
      sphere and of pachymetry in established keratoconus patients using 2 different
      technologies--Scheimpflug imaging with the Pentacam and scanning slit combined
      with Placido imaging with Orbscan IIz. DESIGN: Retrospective comparative case
      series. PARTICIPANTS: Patients with confirmed keratoconus by biomicroscopy and
      Placido topography who had corneal topography scans by the Pentacam and Orbscan
      IIz on their visit from April 2004 to April 2005. These scans were obtained
      routinely for patient diagnosis, treatment, and progression. METHODS: The mean
      difference, standard deviation (SD), and 95% limits of agreement (LOA) were
      calculated, and Bland-Altman plots were constructed for best-fit sphere radius of
      curvature, posterior elevation above the best-fit sphere, and pachymetry of the
      thinnest point. RESULTS: Thirty-six eyes of 29 patients were analyzed. The
      average radius for posterior best-fit sphere was 5.97 microm (range, 4.69-6.79)
      for the Pentacam and 6.00 microm (range, 4.97-6.55) for Orbscan IIz. The mean
      difference (Pentacam - Orbscan IIz) for the radius generated for the best-fit
      sphere was -0.03+/-0.22 SD with a 95% confidence interval (CI) of -0.11 to 0.04
      and a 95% LOA of -0.46 to 0.40 (P = 0.362). The mean posterior elevation by best
      fit sphere fixed to the apex was 34.86 microm (range, 3-120) for the Pentacam and
      48.50 microm (range, 11-118) for Orbscan IIz. The mean difference was -13.64+/
      26.08 SD (95% CI, -22.46 to -4.81; 95% LOA, -64.75 to 37.48; P = 0.003). The
      average thinnest point for the Pentacam was 443.6 microm (range, 164-587), and
      that for Orbscan IIz was 445.9 microm (range, 204-597). The mean difference in
      the thinnest point for the Pentacam and Orbscan IIz was -2.28+/-35.55 (95% CI, 
      14.31 to 9.75; 95% LOA, -71.95 to 67.39; P = 0.703). CONCLUSION: Both the
      Pentacam and Orbscan IIz determine similar thinnest points but have a measurable
      difference in posterior elevations above the best-fit sphere, despite similar
      radii of curvature. This difference may be important in the screening of patients
      for refractive surgery to avoid surgery on patients with early keratoconus. This
      study cannot determine if the Pentacam is underestimating the posterior vault or
      if Orbscan is overestimating this height, and further studies with a standardized
      test object are needed.

PMID- 16949448
TI  - Diplopia after cataract surgery.

PMID- 16949450
TI  - Biostatistics in ophthalmology.

PMID- 16949451
TI  - Diplopia after cataract surgery.

PMID- 16949453
TI  - Cataract surgery techniques.

PMID- 16949454
TI  - Pars plana vitrectomy for RD.

PMID- 16949455
TI  - Glaucoma and intravitreal steroids.

PMID- 16949456
TI  - Teaching applanation tonometry.

PMID- 16949459
TI  - NFL appearance after peeling.

PMID- 16949460
TI  - Orbital compartment syndrome after spinal surgery.

PMID- 16949463
TI  - Pathogenesis of renal anemia.
AB  - Anemia is a common complication of chronic kidney disease. Although mechanisms
      involved in the pathogenesis of renal anemia include chronic inflammation, iron
      deficiency, and shortened half-life of erythrocytes, the primary cause is
      deficiency of erythropoietin (EPO). Serum EPO levels in patients with chronic
      kidney disease are usually within the normal range and thus fail to show an
      appropriate increase with decreasing hemoglobin levels, as found in nonrenal
      anemias. Studies elucidating the regulation of EPO expression led to the
      identification of the hypoxia inducible factor-hypoxia responsive element system.
      However, despite much progress in understanding the molecular mechanisms through
      which cells can sense oxygen availability and translate this information into
      altered gene expression, the reason why EPO production is inappropriately low in
      diseased kidneys remains incompletely understood. Both alterations in the
      function of EPO-producing cells and perturbations of the oxygen-sensing mechanism
      in the kidney may contribute. As with other anemias, the consequences of renal
      anemia are a moderate decrease in tissue oxygen tensions and counterregulatory
      mechanisms that maintain total oxygen consumption, including a persistent
      increase in cardiac output.

PMID- 16949464
TI  - Dialysis adequacy and response to erythropoiesis-stimulating agents: what is the
      evidence base?
AB  - Despite an increase in the use and average dose of erythropoiesis-stimulating
      agents (ESA) over the past 15 years, a substantial percentage of patients still
      do not achieve hemoglobin targets recommended by international guidelines. A
      clear relationship among hemoglobin or hematocrit levels, ESA dose, and increase
      in dialysis dose has been pointed out by a number of prospective or retrospective
      studies. This is particularly true in patients receiving inadequate dialysis.
      Increasing attention also has been paid to the relationship between dialysis,
      increased inflammatory stimulus, and ESA response because dialysate contamination
      and low-compatible treatments may increase cytokine production and consequently
      inhibit erythropoiesis. The biocompatibility of dialysis membranes and flux are
      other important factors. However, in highly selected, adequately dialyzed
      patients without iron or vitamin depletion, the effect of these treatment
      modalities on anemia seems to be smaller than expected. The role of on-line
      treatments still is controversial given that it is still difficult to
      discriminate between the effect of on-line hemodiafiltration per se from that of
      an increased dialysis dose. Very preliminary results obtained with short or long
      nocturnal daily hemodialysis on anemia correction are encouraging.

PMID- 16949465
TI  - The high prevalence of anemia in diabetes is linked to functional erythropoietin
      deficiency.
AB  - Anemia is a common finding in diabetes, particularly in patients with albuminuria
      or renal impairment. We recently showed that at least 1 in 5 outpatients with
      type 1 or type 2 diabetes in tertiary clinics have anemia, in whom it constitutes
      a significant additional burden. Anemia is associated strongly with an increased
      risk of diabetic complications including nephropathy, retinopathy, and heart
      failure. Although a number of factors contribute to an increased prevalence of
      anemia in diabetes, an uncoupling of hemoglobin concentration and renal
      erythropoietin synthesis associated with tubular dysfunction appears to be the
      dominant factor. In our patients with diabetes and anemia, more than three
      quarters had functional erythropoietin deficiency. This association was most
      pronounced in patients with renal impairment, in whom nearly half of all patients
      had anemia. However, 70% of anemic patients without renal impairment also had
      inappropriately low erythropoietin levels. Consequently, the likelihood of
      functional erythropoietin deficiency, as a cause of anemia in patients with
      diabetes, is not dependent on the severity of renal impairment. Although there is
      a clear rationale for correction of anemia in diabetes, it remains to be
      established whether this will lead to improved outcomes. Some small studies
      suggest improvement in cardiac outcomes and hospitalization. It is anticipated
      that large ongoing studies will help define the optimal approach to the
      management of anemia in diabetes.

PMID- 16949466
TI  - Role of anemia in progression of chronic kidney disease.
AB  - Anemia is a well-known consequence of chronic kidney disease (CKD), and its
      prevalence progressively increases when the estimated glomerular filtration rate
      decreases to less than 60 mL/min/1.73 m2. However, analyses of the consequences
      of anemia and of the mechanisms of progression of CKD suggest that anemia also
      could contribute to the deterioration of kidney function. This hypothesis is
      based mostly on experimental data that imply that hypoxia of tubular cells plays
      an important role in tubulointerstitial damage associated with CKD and, thus, in
      the progression of renal failure. It also is supported by the fact that red blood
      cells represent a major antioxidant component of blood and that oxidative stress
      appears to contribute to glomerulosclerosis and tubulointerstitial damage. In
      humans, post hoc analysis of the Reduction of End points in non insulin-dependent
      diabetes mellitus (NIDDM) with the Angiotensin II Antagonist Losartan study and
      analyses of smaller prospective cohorts of CKD patients have shown that anemia is
      an independent risk factor for progression of CKD. In addition, 3 small
      randomized studies have suggested that anemia correction could slow the
      progression of CKD. Thus, the existence of a relationship between anemia and
      progression of CKD is not only plausible biologically, but also is supported by
      observational studies and by small intervention studies. However, only a large,
      randomized, prospective trial will be able to establish if anemia correction can
      slow the progression of CKD effectively.

PMID- 16949467
TI  - Anemia and the heart in chronic kidney disease.
AB  - Cardiovascular disease is highly prevalent at all stages of chronic kidney
      disease (CKD) and is the leading cause of morbidity and mortality. Individuals
      with CKD commonly have multiple risk factors for the development of
      cardiovascular disease, including both traditional and nontraditional risk
      factors. Anemia is a nontraditional cardiovascular risk factor found in CKD that
      contributes to the development and progression of structural abnormalities of the
      heart, namely left ventricular hypertrophy and dilation. In addition, a
      deficiency of erythropoietin per se also may have important pathophysiologic
      consequences. In this review we summarize the evidence from observational studies
      showing an association between anemia and adverse cardiac outcomes at all stages
      of CKD. In addition, we provide an overview of the evidence accumulating from
      randomized controlled trials conducted in both nondialysis and dialysis CKD
      populations evaluating the effect of anemia correction on cardiac outcomes such
      as changes in left ventricular hypertrophy.

PMID- 16949468
TI  - The interaction between heart failure and other heart diseases, renal failure,
      and anemia.
AB  - Anemia, defined as a hemoglobin level of less than 12 g/dL, often is seen in
      congestive heart failure (CHF). It is associated with an increased mortality and
      morbidity and increased hospitalizations. Compared with nonanemic patients the
      presence of anemia also is associated with worse cardiac clinical status, more
      severe systolic and diastolic dysfunction, a higher beta natriuretic peptide
      level, increased extracellular and plasma volume, a more rapid deterioration of
      renal function, a lower quality of life, and increased medical costs. The only
      way to determine if anemia is merely a marker for more severe CHF or actually is
      contributing to the worsening of the CHF is to correct the anemia and see if this
      favorably influences the CHF. In several controlled and uncontrolled studies,
      correction of the anemia with subcutaneous erythropoietin (EPO) or darbepoetin in
      conjunction with oral and intravenous iron has been associated with an
      improvement in clinical status, number of hospitalizations, cardiac and renal
      function, and quality of life. However, larger, randomized, double-blind,
      controlled studies still are needed to verify these initial observations. The
      effect of EPO may be related partly to its nonhematologic functions including
      neovascularization; prevention of apoptosis of endothelial, myocardial, cerebral,
      and renal cells; increase in endothelial progenitor cells; and anti-inflammatory
      and antioxidant effects. Anemia also may play a role in increasing cardiovascular
      morbidity in chronic kidney insufficiency, diabetes, renal transplantation,
      asymptomatic left ventricular dysfunction, left ventricular hypertrophy, acute
      coronary syndromes including myocardial infarction and chronic coronary heart
      disease, and in cardiac surgery. Again, controlled studies of correction of
      anemia are needed to assess its importance in these conditions. The anemia in CHF
      mainly is caused by a combination of renal failure and CHF-induced increased
      cytokine production, and these can both lead to reduced production of EPO,
      resistance of the bone marrow to EPO stimulation, and to cytokine-induced iron
      deficiency anemia caused by reduced intestinal absorption of iron and reduced
      release of iron from iron stores. The use of angiotensin-converting enzyme
      inhibitor and angiotensin receptor blockers also may inhibit the bone marrow
      response to EPO. Hemodilution caused by CHF also may cause a low hemoglobin
      level. Renal failure, cardiac failure, and anemia therefore all interact to cause
      or worsen each other--the so-called cardio-renal-anemia syndrome. Adequate
      treatment of all 3 conditions will slow down the progression of both the CHF and
      the chronic kidney insufficiency.

PMID- 16949469
TI  - Anemia, renal transplantation, and the anemia paradox.
AB  - Anemia is prevalent in renal transplant recipients (RTRs), as it is in all
      chronic kidney disease (CKD) populations. Mild anemia occurs in up to 40% of
      RTRs, and more severe anemia (110 g/L) occurs in about 9% to 22% of patients. As
      in CKD, impaired graft (renal) function is a major predictor of anemia identified
      in nearly all studies, suggesting a major role for erythropoietin deficiency.
      Chronic inflammation, malnutrition, iron deficiency, and medications (angiotensin
      converting enzyme inhibitors, angiotensin receptor blockers, mycophenolate,
      azathioprine, and sirolimus) are contributory factors seen in some, but not all,
      studies. Although pathophysiologic and observational data strongly support a
      causal association between low hemoglobin levels and cardiovascular outcomes in
      RTRs, no randomized controlled trial to date has been able to show a clear
      benefit of anemia treatment on cardiovascular outcomes or mortality in either RTR
      or other CKD populations. This important paradox has led some investigators to
      question the causal nature of the association between anemia and heart disease.
      Resolution of this paradox, at least for patients with stage 2/3 CKD, will depend
      on the outcome of randomized controlled trials currently in progress. Similar
      trials sorely are needed in renal transplant populations. In the interim, current
      opinion favors treating persistent anemia in RTRs to achieve targets similar to
      those recommended for dialysis and CKD patients.

PMID- 16949470
TI  - Recent advances in erythropoietic agents in renal anemia.
AB  - Red cell production in chronic kidney disease is usually too low to maintain a
      normal haemoglobin, and thus anaemia develops in a large proportion of patients.
      The ability to stimulate erythropoiesis in the bone marrow by the use of
      therapeutic agents has only been possible in the last 20 years, initially with
      recombinant human erythropoietin (epoetin), and later darbepoetin alfa. Many new
      agents are, however, in clinical development, and these include CERA, Hematide,
      and HIF stabilisers, in addition to the imminent launch of biosimilar epoetins.
      The main issue with biosimilars is the unknown risk of immunogenicity. CERA is a
      large molecule, approximately twice the size of epoetin, which was created by
      integrating a single polymer chain into the erythropoietin molecule. CERA has a
      much prolonged half-life, and Phase II and III clinical trials have investigated
      administration of CERA every 3 or 4 weeks. Hematide is derived from original
      research on the erythropoietin-mimetic peptides, and is in Phase II of its
      clinical trial programme. Again, this compound is being investigated as a once
      monthly administration. The HIF stabilizers are orally-active inhibitors of the
      enzyme that degrades hypoxia-inducible factor (prolyl hydroxylase), and this
      leads to upregulation of erythropoietin gene expression. Other strategies for
      stimulating erythropoiesis, briefly described in this review, are at an earlier
      stage of development. This is an exciting and rapidly developing area of
      scientific and translational research.

PMID- 16949471
TI  - Iron supplementation in renal anemia.
AB  - Iron-deficiency frequently develops in patients with chronic kidney disease who
      are treated with recombinant human erythropoietin (rHuEPO). It results in reduced
      effectiveness of anemia therapy; patients may fail to reach hemoglobin targets or
      may require excessively large doses of rHuEPO. It has been recognized widely that
      iron management, monitoring for iron deficiency, and effective iron
      supplementation forms a core component of anemia therapy. This review discusses
      the physiology of iron balance, derangements in iron balance in chronic kidney
      disease (CKD), and the diagnosis and treatment of iron deficiency in patients
      treated with rHuEPO.

PMID- 16949472
TI  - Erythropoietin and acute renal failure.
AB  - The hemopoietic growth factor erythropoietin (EPO) has been recognized to be a
      multifunctional cytokine that plays a key role in ischemic preconditioning in the
      brain and heart. The EPO receptor is expressed widely in the kidney, and we
      review the important findings from the use of EPO in experimental models of acute
      renal failure that show that EPO reduces tubular cell death and hence the
      dysfunction induced by ischemia reperfusion injury, and we explore how these
      observations may be translated into the clinical arena.

PMID- 16949474
TI  - Complications of abdominal and pelvic procedures: computed tomographic diagnosis.
AB  - The postprocedural period is a critical time in which serious complications can
      manifest. Localization of suspected complications following abdominal and pelvic
      procedures can be difficult on clinical evaluation alone. For example, abdominal
      pain after a colonoscopy may vary in etiology and can result from simple colonic
      spasm to colonic perforation, hemoperitoneum, or even splenic rupture. Vague
      abdominal pain following a renal biopsy may be due to minimal postprocedural
      bleeding into and around the kidney or may be due to potentially life-threatening
      hemorrhage. In such patients, computed tomography can play a crucial role in the
      rapid identification of complications as well guidance of subsequent patient
      management. The purpose of this article is to demonstrate the benefit of computed
      tomography-assisted diagnosis of complications associated with routine procedures
      performed on or throughout the abdomen and pelvis, including cardiac
      catheterization, colonoscopy, endoscopy, percutaneous biopsy, and interventional
      radiology procedures.

PMID- 16949475
TI  - Sixty-four multi-detector row computed tomography in multitrauma patient imaging:
      early experience.
AB  - Sixty-four multi-detector row computed tomography (64-MDCT) offers the
      possibility of increasing the application of CT in multitrauma imaging. 64-MDCT
      affords significant increases in imaging speed while allowing for subisotropic
      voxel slice thicknesses. We have recently installed two 64-MDCT scanners in our
      Level I trauma center. Our routine protocols using these new scanners are
      detailed. Additionally, this new technology has made possible several novel
      protocols. These include an increased use of CT angiography in trauma imaging.
      The acquisition speed and table lengths available with 64-MDCT allow for whole
      body scout images. These scout images may be used to plan complex, multistep CT
      studies incorporating pelvic and extremity angiography, when indicated, into a
      single study. Imaging speeds afforded by 64-MDCT allow for imaging in any number
      of phases, over any area to be imaged, all with a single initial bolus of
      contrast. Image quality afforded by 64-MDCT allows for increasing roles of MPR
      and 3D reformations. These alternatives to axial images are currently used both
      for primary interpretation by our trauma radiologists as well as for
      communication and use by our clinical colleagues. Technical challenges presented
      by 64-MDCT include further increases in the number of images generated.
      Currently, datasets may exceed 4,000 images when angiography is included in
      routine trauma protocols. Radiation doses are also an ever present concern. With
      the opportunity to image from head to toe in seconds with submillimeter slice
      thicknesses, radiologists must be constantly vigilant in their efforts to limit
      radiation. Novel techniques such as automated dose modulation currently offer
      means of reducing radiation doses. Though several technical challenges are faced,
      64-MDCT represents an evolution in multitrauma imaging.

PMID- 16949476
TI  - Mimicks of pancreatic malignancy in patients with chronic pancreatitis:
      correlation of computed tomography imaging features with histopathologic
      findings.
AB  - Differentiation of chronic pancreatitis and pancreatic carcinoma can be a
      clinical and radiologic dilemma. Several patients with chronic pancreatitis can
      undergo unnecessary major abdominal surgery for benign lesions. This pictorial
      review illustrates the computed tomographic findings and histopathologic features
      of lesions mimicking pancreatic neoplasm in patients with chronic pancreatitis.
      Several benign lesions can simulate pancreatic malignancy in patients with
      chronic pancreatitis. Knowledge of the computed tomographic appearance of these
      benign entities is important to prevent unnecessary surgeries.

PMID- 16949477
TI  - Value of magnetic resonance imaging in muscle trauma.
AB  - While most muscle injuries are recognized clinically, magnetic resonance imaging
      (MRI) is the ideal noninvasive test to assess their extent and severity, which
      impacts therapy and influences prognosis. Typical examples of these injuries
      include muscle contusions, lacerations, sprains, and delayed onset muscle
      soreness. For other less common traumatic muscle conditions (exertional
      compartment syndrome, muscle herniation, and traumatic denervation), the clinical
      findings are often subtle or ambiguous and MRI will indicate the correct
      diagnosis. In patients with known muscle trauma, MRI can detect complications
      such as hematoma or seroma development, scarring and fibrosis, and myositis
      ossificans. This article illustrates the spectrum of muscle injuries, emphasizing
      the value of MRI in their diagnosis.

PMID- 16949478
TI  - ACC/AHA/ESC 2006 guidelines for management of patients with ventricular
      arrhythmias and the prevention of sudden cardiac death: a report of the American
      College of Cardiology/American Heart Association Task Force and the European
      Society of Cardiology Committee for Practice Guidelines (Writing Committee to
      Develop Guidelines for Management of Patients With Ventricular Arrhythmias and
      the Prevention of Sudden Cardiac Death).

PMID- 16949479
TI  - Biomaterials for the treatment of myocardial infarction.
AB  - For nearly a decade, researchers have investigated the possibility of cell
      transplantation for cardiac repair. More recently, the emerging fields of tissue
      engineering and biomaterials have begun to provide potential treatments. Tissue
      engineering approaches are designed to repair lost or damaged tissue through the
      use of growth factors, cellular transplantation, and biomaterial scaffolds. There
      are currently 3 biomaterial approaches for the treatment of myocardial infarction
      (MI). The first involves polymeric left ventricular restraints in the prevention
      of heart failure. The second utilizes in vitro engineered cardiac tissue, which
      is subsequently implanted in vivo. The final approach entails injecting cells
      and/or a scaffold into the myocardium to create in situ engineered cardiac
      tissue. This review gives an overview of the current progress in the growing
      field of biomaterials for the treatment of MI.

PMID- 16949480
TI  - Homocysteine hypothesis for atherothrombotic cardiovascular disease: not
      validated.
AB  - Homocysteine has been implicated in promoting atherosclerotic and thrombotic
      vascular disease. During the last decade, the utility of homocysteine in
      predicting risk for atherothrombotic vascular disease has been evaluated in
      several observational studies in a large number of patients. These studies show
      that the overall risk for vascular disease is small, with prospective,
      longitudinal studies reporting a weaker association between homocysteine and
      atherothrombotic vascular disease compared to retrospective case-control and
      cross-sectional studies. Furthermore, randomized controlled trials of
      homocysteine-lowering therapy have failed to prove a causal relationship. On the
      basis of these results, there is currently insufficient evidence to recommend
      routine screening and treatment of elevated homocysteine concentrations with
      folic acid and other vitamins to prevent atherothrombotic vascular disease. This
      review outlines the metabolism and pathophysiology of homocysteine, highlights
      the results of homocysteine observational and interventional trials, and presents
      areas of uncertainty and potential future work.

PMID- 16949481
TI  - Renal toxicity evaluation and comparison between visipaque (iodixanol) and
      hexabrix (ioxaglate) in patients with renal insufficiency undergoing coronary
      angiography: the RECOVER study: a randomized controlled trial.
AB  - OBJECTIVES: This study sought to compare the nephrotoxicity of iodixanol and
      ioxaglate in patients with renal impairment undergoing coronary angiography.
      BACKGROUND: Iodixanol, a nonionic, dimeric, iso-osmolar contrast medium (IOCM),
      may be less nephrotoxic than low-osmolar contrast media (LOCM) in high-risk
      patients. METHODS: In a prospective, randomized trial in 300 adults with
      creatinine clearance (CrCl) < or =60 ml/min, patients received either iodixanol
      or ioxaglate and underwent coronary angiography with or without percutaneous
      coronary intervention. The primary end point was the incidence of contrast
      induced nephropathy (CIN) (an increase in serum creatinine [SCr] > or =25% or >
      or =0.5 mg/dl [> or =44.2 mumol/l]). The incidence of CIN in patients with severe
      renal impairment at baseline (CrCl <30 ml/min) or diabetes and in those receiving
      large doses (> or =140 ml) of contrast medium was also determined. RESULTS: The
      incidence of CIN was significantly lower with iodixanol (7.9%) than with
      ioxaglate (17.0%; p = 0.021), corresponding to an odds ratio (OR) of CIN of 0.415
      (95% confidence interval [CI] 0.194 to 0.889) for iodixanol. The incidence of CIN
      was also significantly lower with iodixanol in patients with severe renal
      impairment (p = 0.023) or concomitant diabetes (p = 0.041), or in patients given
      > or =140 ml of contrast media (p = 0.038). Multivariate analysis identified use
      of ioxaglate (OR 2.65, 95% CI 1.11 to 6.33, p = 0.028), baseline SCr, mg/dl (OR
      2.0, 95% CI 1.04 to 3.85, p = 0.038), and left ventricular ejection fraction, %
      (OR 0.97, 95% CI 0.94 to 0.99, p = 0.019) as independent risk factors for CIN.
      CONCLUSIONS: The IOCM iodixanol was significantly less nephrotoxic than
      ioxaglate, an ionic, dimeric LOCM. (The RECOVER Trial; http://clinicaltrials.gov;
      NCT00247325).

PMID- 16949482
TI  - A randomized comparison of high clopidogrel loading doses in patients with non-ST
      segment elevation acute coronary syndromes: the ALBION (Assessment of the Best
      Loading Dose of Clopidogrel to Blunt Platelet Activation, Inflammation and
      Ongoing Necrosis) trial.
AB  - OBJECTIVES: We sought to compare the antiplatelet effects of three clopidogrel
      loading doses (LDs). BACKGROUND: Administration of a 300-mg clopidogrel LD is
      beneficial in situations requiring rapid platelet inhibition. Whether higher LDs
      can provide further benefits remains unknown. METHODS: Patients (n = 103) with
      non-ST-segment elevation acute coronary syndromes were randomized to receive a
      300-mg, 600-mg, or 900-mg clopidogrel LD, given on top of other standard therapy
      (including acetylsalicylic acid). The main outcome measure was inhibition of
      adenosine diphosphate-induced inhibition of platelet aggregation (IPA);
      inhibition of platelet activation, inflammatory markers, troponin I release, and
      major adverse cardiac events also were evaluated; all measures were blindly
      evaluated. RESULTS: Compared with the 300-mg LD, greater doses were associated
      with significantly greater platelet inhibition, with dose-effect relationships
      observed for onset of action, maximal plateau, 24-h areas under the curves of
      IPA, and rates of low IPA (<10% at 6 h), using 20 micromol/l major adverse
      cardiac events. A significant dose-response was also observed for the vasodilator
      stimulated phosphoprotein index, a measure of P2Y(12) receptor inhibition.
      Similar but nonsignificant trends were observed for troponin release and major
      adverse cardiac events. Bleeding rates were similar in each group. CONCLUSIONS:
      In low-to-moderate risk patients with non-ST-elevation acute coronary syndromes,
      clopidogrel LDs >300 mg provide a faster onset of action, a higher IPA plateau,
      and greater reductions in platelet activation during the first 24 h. A 900-mg LD
      may induce a greater antiplatelet effect than 600 mg, when compared with the
      standard 300-mg regimen. These findings require further clinical confirmation.

PMID- 16949483
TI  - Short- and long-term risk stratification in acute coronary syndromes: the added
      value of quantitative ST-segment depression and multiple biomarkers.
AB  - OBJECTIVES: The purpose of this study was to develop 30-day and 1-year risk
      stratification models for non-ST-segment elevation acute coronary syndrome (NSTE
      ACS) patients that incorporate quantitative ST-segment depression and novel
      biomarkers. BACKGROUND: Several novel biomarkers have changed the risk profile of
      ACS; thus, the reassessment of traditional indicators such as ST-segment
      depression in this new context is warranted. METHODS: Multivariable logistic
      regression was used to identify significant predictors of 30-day death and
      death/myocardial infarction (MI) and 1-year mortality in 7,800 NSTE-ACS patients
      enrolled in the GUSTO-IV (Global Utilization of Strategies to Open Occluded
      Arteries-IV ACS) trial between 1998 and 2000. RESULTS: Among all other
      predictors, the degree of ST-segment depression had the highest prognostic value
      for 30-day death, 30-day death/MI, and 1-year death. Troponin T (TnT), creatinine
      clearance, N-terminal pro-brain natriuretic peptide (NT-proBNP), heart rate, and
      age were also highly influential on adverse outcomes. Unlike TnT and NT-proBNP, C
      reactive protein was only predictive of long-term death. In contrast to
      mortality, the contribution of TnT to predicting 30-day death/MI increased,
      whereas NT-proBNP's role was attenuated. The discriminatory power was excellent
      (c-index [adjusted for over-optimism]: 0.82 [30-day death]; 0.72 [30-day
      death/MI]; 0.81 [1-year]). CONCLUSIONS: In this large contemporary study of NSTE
      ACS patients, novel insights into risk stratification were observed-in
      particular, the utility of quantitative ST-segment depression and multiple
      biomarkers. Collection of these indicators in future NSTE-ACS populations is
      recommended to evaluate generalizability and clinical application of these
      findings.

PMID- 16949484
TI  - Clinical judgment and treatment options in stable multivessel coronary artery
      disease: results from the one-year follow-up of the MASS II (Medicine,
      Angioplasty, or Surgery Study II).
AB  - OBJECTIVES: This study examined the predictive power of clinical judgment in the
      incidence of cardiovascular end points in a group of individuals with multivessel
      coronary artery disease (CAD) followed up in the MASS II (Medicine, Angioplasty,
      or Surgery Study II). BACKGROUND: There is still no consensus on the best
      treatment for patients with stable multivessel CAD and preserved left ventricular
      function. METHODS: Preferred treatment allocation was recorded for each of the
      611 randomized patients in the MASS II trial before randomization. We have
      divided our sample according to physician-guided decision and randomization
      result into two categories: concordant or discordant. The incidence of the points
      of cardiac death, myocardial infarction, and refractory angina was compared
      between concordant and discordant patients. RESULTS: The number of concordant
      individuals was 292 (48.2%), and this number was not different between the three
      studied treatments (p = 0.11). A significant difference (p = 0.02) was disclosed
      because of an increased incidence of combined end point events in discordant
      patients. In the multivariate Cox hazard model, clinical judgment was a powerful
      predictor of outcome (p = 0.01) even after adjustment for other covariates. The
      main subgroup explaining this difference was a significant shift toward a worse
      outcome in the subgroup of discordant patients who underwent percutaneous
      coronary intervention (PCI) (p = 0.003). CONCLUSIONS: Angiographic variables were
      more often used in making clinical decisions regarding PCI than clinical
      variables, and the only independent predictor of concordance status in the PCI
      group was the number of diseased vessels (p = 0.01). Our data are a reminder that
      physician judgment remains an important predictor of outcomes.

PMID- 16949485
TI  - Physician judgment in cardiology: the art of medicine lives on.

PMID- 16949486
TI  - Effects of metformin on microvascular function and exercise tolerance in women
      with angina and normal coronary arteries: a randomized, double-blind, placebo
      controlled study.
AB  - OBJECTIVES: This study sought to determine whether metformin improves vascular
      function or myocardial ischemia in nondiabetic subjects. BACKGROUND: Metformin
      prevents diabetes and may reduce coronary events in patients with diabetes, but
      effects on microvascular function and angina are not clear. METHODS: We conducted
      an 8-week double-blind, randomized, placebo-controlled study of metformin 500 mg
      twice a day in 33 nondiabetic women with a prior history of normal coronary
      angiography but two consecutive positive (ST-segment depression > or =1 mm)
      exercise tolerance tests. All parameters were measured at baseline and at 8
      weeks, together with an in vivo assessment of forearm (skin) microvascular
      function using laser Doppler imaging combined with iontophoresis. RESULTS: In
      comparison with placebo (n = 17), metformin recipients (n = 16) showed
      significant reductions in weight and in homeostatic model assessment for insulin
      resistance (p < 0.05, intention to treat). Endothelium-dependent microvascular
      responses improved significantly with metformin (2-way repeated analysis of
      variance, p = 0.0003), but responses with placebo were unchanged (p = 0.50). A
      comparison of change in acetylcholine responses between metformin and placebo
      recipients was significant, whether analyzed by a 2-way analysis of variance (p <
      0.0001) or change in area under curves (mean change +392 perfusion units, 95%
      confidence interval [CI] 20 to 764). Endothelium-independent responses were not
      altered. Maximal ST-segment depression (-0.84 mm, 95% CI -1.49 to -0.20, p =
      0.013), Duke score (6.1 U, 95% CI 1.8 to 10.5, p = 0.008), and chest pain
      incidence (-0.11 episodes/day, 95% CI -0.22 to 0.00, p = 0.056) improved in
      metformin relative to placebo recipients. CONCLUSIONS: Metformin may improve
      vascular function and decrease myocardial ischemia in nondiabetic women with
      chest pain and angiographically normal coronary arteries. Larger controlled
      trials of longer duration are warranted.

PMID- 16949487
TI  - Should major vascular surgery be delayed because of preoperative cardiac testing
      in intermediate-risk patients receiving beta-blocker therapy with tight heart
      rate control?
AB  - OBJECTIVES: The purpose of this study was to assess the value of preoperative
      cardiac testing in intermediate-risk patients receiving beta-blocker therapy with
      tight heart rate (HR) control scheduled for major vascular surgery. BACKGROUND:
      Treatment guidelines of the American College of Cardiology/American Heart
      Association recommend cardiac testing in these patients to identify subjects at
      increased risk. This policy delays surgery, even though test results might be
      redundant and beta-blockers with tight HR control provide sufficient myocardial
      protection. Furthermore, the benefit of revascularization in high-risk patients
      is ill-defined. METHODS: All 1,476 screened patients were stratified into low
      risk (0 risk factors), intermediate-risk (1 to 2 risk factors), and high-risk (>
      or =3 risk factors). All patients received beta-blockers. The 770 intermediate
      risk patients were randomly assigned to cardiac stress-testing (n = 386) or no
      testing. Test results influenced management. In patients with ischemia,
      physicians aimed to control HR below the ischemic threshold. Those with extensive
      stress-induced ischemia were considered for revascularization. The primary end
      point was cardiac death or myocardial infarction at 30-days after surgery.
      RESULTS: Testing showed no ischemia in 287 patients (74%); limited ischemia in 65
      patients (17%), and extensive ischemia in 34 patients (8.8%). Of 34 patients with
      extensive ischemia, revascularization before surgery was feasible in 12 patients
      (35%). Patients assigned to no testing had similar incidence of the primary end
      point as those assigned to testing (1.8% vs. 2.3%; odds ratio [OR] 0.78; 95%
      confidence interval [CI] 0.28 to 2.1; p = 0.62). The strategy of no testing
      brought surgery almost 3 weeks forward. Regardless of allocated strategy,
      patients with a HR <65 beats/min had lower risk than the remaining patients (1.3%
      vs. 5.2%; OR 0.24; 95% CI 0.09 to 0.66; p = 0.003). CONCLUSIONS: Cardiac testing
      can safely be omitted in intermediate-risk patients, provided that beta-blockers
      aiming at tight HR control are prescribed.

PMID- 16949488
TI  - Any need for preoperative cardiac testing in intermediate-risk patients with
      tight beta-adrenergic blockade?

PMID- 16949489
TI  - Is plasma oxidized low-density lipoprotein, measured with the widely used
      antibody 4E6, an independent predictor of coronary heart disease among U.S. men
      and women?
AB  - OBJECTIVES: Our aim was to examine whether circulating oxidized low-density
      lipoprotein (oxLDL) is a predictor of coronary heart disease (CHD) independent of
      lipid markers and to compare oxLDL, apolipoprotein B100 (apoB), and total
      cholesterol (TC)/high-density lipoprotein-cholesterol (HDL-C) ratio as predictors
      of CHD. BACKGROUND: Measurement of circulating oxLDL with antibody 4E6, has been
      widely used in many studies; however, few large prospective studies have examined
      whether this marker is a predictor of CHD independent of lipids and compared
      oxLDL with other important lipid predictors. METHODS: After 6 years of follow-up
      among 18,140 men from the HPFS (Health Professionals Follow-up Study) and 8 years
      among 32,826 women from the Nurses' Health Study who provided blood samples at
      baseline, we identified incident nonfatal myocardial infarction or fatal CHD in
      266 men and 235 women. Each case was matched with two control subjects by age,
      smoking, and time of blood draw. The oxLDL was measured via enzyme-linked
      immunosorbent assay with antibody 4E6 against oxidized apoB. RESULTS: Among both
      men and women, oxLDL was significantly related to risk of CHD in multivariate
      analysis before adjustment for any lipid markers. However, when oxLDL, LDL
      cholesterol, HDL-C, and triglycerides were mutually adjusted, oxLDL was no longer
      predictive. When oxLDL and apoB were mutually adjusted, only apoB was predictive
      of CHD. Similar results were found when oxLDL and TC/HDL-C ratio were mutually
      adjusted. CONCLUSIONS: Our results suggest that circulating oxLDL, measured with
      antibody 4E6, is not an independent overall predictor of CHD after adjustment of
      lipid markers and is less predictive in development of CHD than apoB and TC/HDL-C
      ratio.

PMID- 16949490
TI  - Oxidized or native low-density lipoprotein cholesterol: which is more important
      in atherogenesis?

PMID- 16949491
TI  - Lack of inertia force of late systolic aortic flow is a cause of left ventricular
      isolated diastolic dysfunction in patients with coronary artery disease.
AB  - OBJECTIVES: We investigated whether a lack of inertia force of late systolic
      aortic flow and/or apical asynergy provoke early diastolic dysfunction in
      patients with coronary artery disease (CAD). BACKGROUND: Left ventricular (LV)
      isolated diastolic dysfunction is a well-recognized cause of heart failure.
      METHODS: We evaluated LV apical wall motion and obtained left ventricular
      ejection fraction (LVEF) by left ventriculography in 101 patients who underwent
      cardiac catheterization to assess CAD. We also computed the LV relaxation time
      constant (Tp) and the inertia force of late systolic aortic flow from the LV
      pressure (P)-first derivative of left ventricular pressure (dP/dt) relation.
      Using color Doppler echocardiography, we measured the propagation velocity of LV
      early diastolic filling flow (Vp). Patients with LVEF > or =50% (preserved
      systolic function [PSF], n = 83) were divided into 2 subgroups: patients with
      inertia force (n = 53) and without inertia force (n = 30). No patient with
      systolic dysfunction (SDF) (LVEF <50%) had inertia force (n = 18). RESULTS: The
      Tp was significantly longer in patients with SDF (85.7 +/- 21.0 ms) and with PSF
      without inertia force (81.1 +/- 23.6 ms) than in those with PSF with inertia
      force (66.3 +/- 12.8 ms) (p< 0.001). The Vp was significantly less in the former
      2 groups than in the last group. In patients with PSF, LV apical wall motion
      abnormality was less frequently observed in those with inertia force than in
      those without (p < 0.0001). CONCLUSIONS: An absence of inertia force in patients
      with PSF is one of the causes of isolated diastolic dysfunction in patients with
      CAD. Normal LV apical wall motion is substantial enough to give inertia to late
      systolic aortic flow.

PMID- 16949492
TI  - A randomized clinical trial of trimetazidine, a partial free fatty acid oxidation
      inhibitor, in patients with heart failure.
AB  - OBJECTIVES: This study sought to assess whether the long-term addition of
      trimetazidine to conventional treatment could improve functional class, exercise
      tolerance, and left ventricular function in patients with heart failure (HF).
      BACKGROUND: Previous small studies have shown that trimetazidine may be
      beneficial in terms of left ventricular function preservation and control of
      symptoms in patients with post-ischemic HF. METHODS: Fifty-five patients with HF
      were randomly allocated in an open-label fashion to either conventional therapy
      plus trimetazidine (20 mg three times daily) (28 patients) or conventional
      therapy alone (27 patients). Mean follow-up was 13 +/- 3 months. At study entry
      and at follow-up, all patients underwent exercise testing and two-dimensional
      echocardiography. Among the others, New York Heart Association (NYHA) functional
      class and ejection fraction (EF) were evaluated. RESULTS: In the trimetazidine
      group, NYHA functional class significantly improved compared with the
      conventional therapy group (p < 0.0001). Treatment with trimetazidine
      significantly decreased left ventricular end-systolic volume (from 98 +/- 36 ml
      to 81 +/- 27 ml, p = 0.04) and increased EF from 36 +/- 7% to 43 +/- 10% (p =
      0.002). On the contrary, in the conventional therapy group, both left ventricular
      end-diastolic and -systolic volumes increased from 142 +/- 43 ml to 156 +/- 63
      ml, p = 0.2, and from 86 +/- 34 ml to 104 +/- 52 ml, p = 0.1, respectively;
      accordingly, EF significantly decreased from 38 +/- 7% to 34 +/- 7% (p = 0.02).
      CONCLUSIONS: In conclusion, long-term trimetazidine improves functional class and
      left ventricular function in patients with HF. This benefit contrasts with the
      natural history of the disease, as shown by the decrease of EF in patients on
      standard HF therapy alone.

PMID- 16949493
TI  - Metabolic approach in heart failure: rethinking how we translate from theory to
      clinical practice.

PMID- 16949494
TI  - Verapamil versus digoxin and acute versus routine serial cardioversion for the
      improvement of rhythm control for persistent atrial fibrillation.
AB  - OBJECTIVES: The VERDICT (Verapamil Versus Digoxin and Acute Versus Routine Serial
      Cardioversion Trial) is a prospective, randomized study to investigate whether:
      1) acutely repeated serial electrical cardioversions (ECVs) after a relapse of
      atrial fibrillation (AF); and 2) prevention of intracellular calcium overload by
      verapamil, decrease intractability of AF. BACKGROUND: Rhythm control is desirable
      in patients suffering from symptomatic AF. METHODS: A total of 144 patients with
      persistent AF were included. Seventy-four (51%) patients were randomized to the
      acute (within 24 h) and 70 (49%) patients to the routine serial ECVs, and 74
      (51%) patients to verapamil and 70 (49%) patients to digoxin for rate control
      before ECV and continued during follow-up (2 x 2 factorial design). Class III
      antiarrhythmic drugs were used after a relapse of AF. Follow-up was 18 months.
      RESULTS: At baseline, there were no significant differences between the groups,
      except for beta-blocker use in the verapamil versus digoxin group (38% vs. 60%,
      respectively, p = 0.01). At follow-up, no difference in the occurrence of
      permanent AF between the acute and the routine cardioversion groups was observed
      (32% [95% confidence intervals (CI)] 22 to 44) vs. 31% [95% CI 21 to 44],
      respectively, p = NS), and also no difference between the verapamil- and the
      digoxin-randomized patients (28% [95% CI 19 to 40] vs. 36% [95% CI 25 to 48]
      respectively, p = NS). Multivariate Cox regression analysis revealed that lone
      digoxin use was the only significant predictor of failure of rhythm control
      treatment (hazard ratio 2.2 [95% CI 1.1 to 4.4], p = 0.02). CONCLUSIONS: An acute
      serial cardioversion strategy does not improve long-term rhythm control in
      comparison with a routine serial cardioversion strategy. Furthermore, verapamil
      has no beneficial effect in a serial cardioversion strategy.

PMID- 16949495
TI  - P-wave morphology in focal atrial tachycardia: development of an algorithm to
      predict the anatomic site of origin.
AB  - OBJECTIVES: The purpose of this study was to perform a detailed analysis of the P
      wave morphology (PWM) in focal atrial tachycardia (AT) and construct and
      prospectively evaluate an algorithm for identification of the anatomic site of
      origin. BACKGROUND: Although smaller studies have described the PWM from
      particular anatomic locations, a detailed algorithm characterizing the likely
      location of a tachycardia associated with a P-wave of unknown origin has been
      lacking. METHODS: The PWMs for 126 consecutive patients undergoing successful
      radiofrequency ablation of 130 ATs are reported. P waves were included only when
      the onset was preceded by a discernible isoelectric segment. P waves were
      classified as positive (+), negative (-), isoelectric, or biphasic. Sensitivity,
      specificity, and predictive values were calculated. On the basis of these
      results, an algorithm was constructed and prospectively evaluated in 30 new
      consecutive ATs. RESULTS: The distribution of ATs was right atrial (RA) in 82 of
      130 (63%) and left atrial (LA) in 48 of 130 (37%). Right atrial sites included
      crista (n = 28), tricuspid annulus (n = 29), coronary sinus (CS) ostium (n = 14),
      perinodal (n = 7), right septum (n = 1), and RA appendage (n= 3). Left atrial
      sites included pulmonary veins (n = 32), mitral annulus (n = 8), CS body (n= 3),
      left septum (n = 3), and LA appendage (n = 2). In electrocardiographic lead V1, a
      negative or +/- P-wave demonstrated a specificity of 100% for a RA focus, and a +
      or -/+ P-wave demonstrated a sensitivity of 100% for a LA focus. A characteristic
      PWM was associated with high sensitivity and specificity at common atrial sites
      for tachycardia foci. A P-wave algorithm correctly identified the focus in 93%.
      CONCLUSIONS: Characteristic PWMs corresponding to known anatomic sites for focal
      AT are associated with high specificity and sensitivity. A P-wave algorithm
      correctly identified the site of tachycardia origin in 93%.

PMID- 16949496
TI  - Coronary artery calcification and myocardial perfusion in asymptomatic adults:
      the MESA (Multi-Ethnic Study of Atherosclerosis).
AB  - OBJECTIVES: This study assessed the cross-sectional association between coronary
      artery calcification (CAC) and myocardial perfusion in an asymptomatic
      population. BACKGROUND: Clinical studies showed that the prevalence of stress
      induced ischemia increased with CAC burden among patients with coronary heart
      disease (CHD). Whether an association between CAC and myocardial perfusion exists
      in subjects without a history of CHD remains largely unknown. METHODS: A total of
      222 men and women, ages 45 to 84 years old and free of CHD diagnosis, in the
      Minnesota field center of the MESA (Multi-Ethnic Study of Atherosclerosis) were
      studied. Myocardial blood flow (MBF) was measured using magnetic resonance
      imaging during rest and adenosine-induced hyperemia. Perfusion reserve was
      calculated as the ratio of hyperemic to resting MBF. Agatston CAC score was
      determined from chest multidetector computed tomography. RESULTS: Mean values of
      hyperemic MBF and perfusion reserve, but not resting MBF, were monotonically
      lower across increasing CAC levels. After adjusting for age and gender, odds
      ratios (95% confidence intervals) of reduced perfusion reserve (<2.5) for
      subjects with CAC scores of 0, 0.1 to 99.9, 100 to 399, and > or =400 were 1.00
      (reference), 2.16 (0.96 to 4.84), 2.81 (1.04 to 7.58), and 4.99 (1.73 to 14.4),
      respectively. Further adjustment for other coronary risk factors did not
      substantially modify the association. However, the inverse association between
      perfusion reserve and CAC attenuated with advancing age (p for interaction <
      0.05). CONCLUSIONS: Coronary vasodilatory response was associated inversely with
      the presence and severity of CAC in asymptomatic adults. Myocardial perfusion
      could be impaired by or manifest the progression to subclinical coronary
      atherosclerosis in the absence of clinical CHD.

PMID- 16949497
TI  - Coronary artery calcification and myocardial perfusion: kissing cousins or
      distant relatives?

PMID- 16949498
TI  - What is the prognostic value of myocardial perfusion imaging using rubidium-82
      positron emission tomography?
AB  - OBJECTIVES: The objective was to determine the prognostic value of rubidium-82
      (82Rb) positron emission tomography (PET) myocardial perfusion imaging (MPI).
      BACKGROUND: 82Rb PET MPI accurately diagnoses coronary artery disease (CAD).
      However, there are limited data evaluating its prognostic value. METHODS: Follow
      up (3.1 +/- 0.9 years) was obtained in 367 patients who underwent dipyridamole
      82Rb PET MPI. Patients were divided into groups based on their summed stress
      score (SSS): group I, normal (<4); group II, mild (4 to 7); and group III,
      moderate (8 to 11) to severe (> or =12). RESULTS: There were significant
      differences among patients in the 3 SSS groups for hard events (cardiac death and
      myocardial infarction [MI]) (p < 0.001) and total cardiac events (hard events,
      revascularization and hospitalization) (p < 0.001). The annual hard events rates
      were 0.4%, 2.3%, and 7.0% in the normal, mild, and moderate-severe groups,
      respectively. In adjusted survival models, 82Rb PET SSS was the strongest
      predictor of total cardiac events and a significant predictor of hard events.
      Among patients referred for PET after 99mTc single-photon emission computed
      tomography, the annual total event rate was higher with abnormal versus normal
      SSS on PET (15.2% vs. 1.3%, p < 0.001). In patients with obesity, the annual
      total event rate was 11.1% with an abnormal scan and 1.5% with a normal scan (p <
      0.001). CONCLUSIONS: This study shows that 82Rb PET MPI has significant
      prognostic value for predicting cardiac events, including death and MI. It also
      seems to have prognostic value in patients whose diagnosis remains uncertain
      after single-photon emission computed tomography MPI and in obese patients. The
      prognostic value of PET MPI may improve the management of cardiac patients.

PMID- 16949499
TI  - Atrial flutter in infants.
AB  - OBJECTIVES: We sought to characterize the clinical nature of atrial flutter (AFL)
      in a large cohort of infants. BACKGROUND: There are no large studies describing
      the natural history of AFL in infants. Previous studies vary in the therapy used
      and expected prognosis. METHODS: We reviewed the records of all children younger
      than 1 year of age who were diagnosed with AFL at our hospital during the past 25
      years, excluding those with previous cardiac surgery. RESULTS: We identified 50
      infants with AFL. Most, 36 (72%), presented within the first 48 h of life.
      Congestive heart failure was evident in 10 infants, with 6 presenting at 1 day of
      age, and 4 presenting beyond 1 month of age. The remainder were asymptomatic. A
      large atrial septal defect was the only structural heart disease. Spontaneous
      conversion to sinus rhythm occurred in 13 (26%) infants. Sinus rhythm was
      restored in 20 of 23 (87%) attempts at direct current cardioversion and 7 of 22
      (32%) attempts at transesophegeal pacing; 7 required antiarrhythmic therapy. An
      additional arrhythmia, all supraventricular, appeared in 11 (22%) infants. The
      recurrence of AFL developed in 6 infants; 5 of 6 of these incidents occurred
      within 24 h of the first episode. All patients with recurrence had an additional
      arrhythmia. CONCLUSIONS: Infants with AFL usually present within the first 2 days
      of life. No association was found with structural heart disease. Direct current
      cardioversion appears to be most effective at establishing sinus rhythm. Chronic
      AFL has the potential to cause cardiovascular compromise. Atrial flutter in the
      absence of other arrhythmias has a low risk of recurrence. Once in sinus rhythm,
      infants with AFL have an excellent prognosis and may not require chronic
      antiarrhythmic therapy.

PMID- 16949500
TI  - Corrected QT variability in serial electrocardiograms in long QT syndrome: the
      importance of the maximum corrected QT for risk stratification.
AB  - OBJECTIVES: We evaluated the incremental prognostic information provided by
      multiple corrected QT (QTc) measurements on serial electrocardiograms (ECGs) in
      patients with the inherited long QT syndrome (LQTS). BACKGROUND: A baseline QTc
      of > or =500 ms has been shown to be associated with increased risk of cardiac
      events among LQTS patients. However, the value of QTc measurements on follow-up
      ECGs in risk assessment has not been determined. METHODS: The risk of a first
      LQTS-related cardiac event during adolescence was assessed in 375 patients
      enrolled in the International LQTS Registry for whom serial follow-up ECGs were
      recorded before age 10. RESULTS: The mean +/- SD difference between the minimum
      and maximum QTc values on serial ECGs recorded in study patients was 47 +/- 40
      ms. The maximum QTc interval recorded before age 10 was the strongest predictor
      of cardiac events during adolescence (adjusted hazard ratio [HR] = 2.74; p <
      0.001). Other follow-up QTc measures, including the baseline, the mean, and the
      most recent QTc interval recorded before age 10, were less significant risk
      factors. After adjusting for the maximum QTc value during follow-up, no
      significant association remained between the baseline QTc value and the risk of
      subsequent cardiac events (HR = 1.04; p = 0.91). CONCLUSIONS: In LQTS patients,
      there is a considerable variability in QTc measures in serial follow-up ECGs. The
      maximum QTc interval provides incremental prognostic information beyond the
      baseline measurement. We suggest that risk stratification in LQTS patients should
      include follow-up ECG data.

PMID- 16949501
TI  - QT interval duration remains a major risk factor in long QT syndrome patients.

PMID- 16949502
TI  - President's page: a new home for the American College of Cardiology.

PMID- 16949503
TI  - Trials and tribulations of noninferiority: the ximelagatran experience.

PMID- 16949505
TI  - Decompensated heart failure and diuretic resistance.

PMID- 16949506
TI  - Amino-terminal pro-brain natriuretic peptide to diagnose congestive heart failure
      in patients with impaired kidney function.

PMID- 16949510
TI  - Interaction among risk-time and benefit of primary angioplasty.

PMID- 16949512
TI  - Populism in guideline writing.

PMID- 16949513
TI  - Trends in the management of arterial hypertension in patients with type 1 and
      insulin-treated type 2 diabetes mellitus over a period of 10 years (1989/1990
      1994/1995). Results of the JEVIN trial.
AB  - For populations of patients with insulin-treated diabetes mellitus, information
      about the quality of blood pressure control, an independent risk factor for
      cardiovascular mortality and morbidity, is widely lacking. Hence, it was the goal
      of the trial to evaluate the prevalence of arterial hypertension, the quality of
      blood pressure control and changes in treatment modalities over a period of 10
      years. PATIENTS AND METHODS: In 1989/1990, Jena's St. Vincent (JEVIN) Trial
      started as a prospective, population-based survey with 10-year follow-up of all
      patients with type 1 and insulin-treated type 2 diabetes mellitus aged 16 to 60
      years and living in the city of Jena, Thuringia, Germany. RESULTS: In 1999/2000,
      46 (40.4%) of 114 patients with type 1 and 104 (70.7%) of 147 patients with
      insulin-treated type 2 diabetes were on blood pressure-lowering drugs.
      Hypertension prevalence in the total population was 57.5%. It was higher in
      patients with insulin-treated type 2 than in type 1 diabetes (47.4% vs. 78.9%,
      P<.001). In 1999/2000, the number of patients with type 1, but also type 2,
      diabetes on blood pressure-lowering agents was higher than in 1994/1995 and
      1989/1990. In the whole group, the mean blood pressure improved from 1989/1990 up
      to 1994/1995 and has remained constant up to the follow-up examination in
      1999/2000. In 1999/2000, of those with arterial hypertension, blood pressure was
      higher than the 140/90-mm Hg target in 17.5% (20/114) of the patients with type 1
      and in 42.2% (62/147) of the patients with insulin-treated type 2 diabetes.
      CONCLUSIONS: The JEVIN trial provides a useful population-based summary of the
      quality of blood pressure and metabolic control of patients with insulin-treated
      diabetes. Although the trial demonstrates an impressive improvement in the
      quality of blood pressure and metabolic control over the last decade, it also
      shows various problems: In many patients, both with type 1 and type 2 diabetes
      mellitus, a good blood pressure control (below 140/90 mm Hg) has not been
      achieved. Moreover, drug therapy, in particular concerning patients with overt
      nephropathy, is often inappropriate.

PMID- 16949514
TI  - Carotid artery intima-media complex thickening in patients with relatively long
      surviving type 1 diabetes mellitus.
AB  - OBJECTIVE: The factors responsible for premature coronary atherosclerosis in
      patients with type 1 diabetes are ill defined. We therefore assessed carotid
      intima-media complex thickness (IMT) in relatively long-surviving patients with
      type 1 diabetes as a marker of atherosclerosis and correlated this with
      traditional risk factors. DESIGN: Cross-sectional study of 148 patients with
      relatively long-surviving (>18 years) type 1 diabetes (76 men and 72 women)
      attending the Centre for Diabetes and Endocrinology, Johannesburg. METHODS: The
      mean common carotid artery IMT and presence or absence of plaque was evaluated by
      high-resolution B-mode ultrasound. Their median age was 48 years and duration of
      diabetes 26 years (range 18-59 years). Traditional risk factors (age, duration of
      diabetes, glycemic control, hypertension, smoking and lipoprotein concentrations)
      were recorded. Three response variables were defined and modeled. Standard
      multiple regression was used for a continuous IMT variable, logistic regression
      for the presence/absence of plaque and ordinal logistic regression to model three
      categories of "risk." RESULTS: The median common carotid IMT was 0.62 mm (range
      0.44-1.23 mm) with plaque detected in 28 cases. The multiple regression model
      found significant associations between IMT and current age (P=.001), duration of
      diabetes (P=.033), BMI (P=.008) and diagnosed hypertension (P=.046) with HDL
      showing a protective effect (P=.022). Current age (P=.001) and diagnosed
      hypertension (P=.004), smoking (P=.008) and retinopathy (P=.033) were significant
      in the logistic regression model. Current age was also significant in the ordinal
      logistic regression model (P<.001), as was total cholesterol/HDL ratio (P<.001)
      and mean HbA(1c) concentration (P=.073). CONCLUSIONS: The major factors
      influencing common carotid IMT in patients with relatively long-surviving type 1
      diabetes are age, duration of diabetes, existing hypertension and HDL
      (protective) with a relatively minor role ascribed to relatively long-standing
      glycemic control.

PMID- 16949515
TI  - Assessment of the relationship between glucose and A1c using kinetic modeling.
AB  - Treatment goals for diabetic patients are directed towards lowering A1c values by
      controlling blood glucose concentrations (BGC), making it important to understand
      the relationship between the two parameters. Because findings from clinical
      trials about the relationship between BGC and A1c values show a profound
      variability around the obtained regression lines, they are difficult to apply to
      individual patients. Therefore, a model was developed and applied based on the
      kinetics of HbA1c formation and removal. It takes the instability of A1c and loss
      of hemoglobin into consideration. Data from clinical studies and hypothetical
      scenarios were used to test the model and to describe the relationship between
      A1c and BGC. A close agreement between experimental and calculated data was
      obtained in steady-state and non-steady-state conditions. Aside the erythrocyte
      life span, the chemical instability of A1c appears to affect A1c levels markedly
      and their changes due to therapy. A threefold increase in BGC over 30 days prior
      to A1c measurement can cause an increase in A1c value of about 120% as compared
      with 4% when it occurs 4 months prior to A1c measurement. Profound daily
      fluctuations in BGC result in minor changes in A1c. In conclusion, A1c provides
      information about a patient's glycemia, mainly over the past 2 months, and may
      not reflect well daily blood glucose fluctuations. This model might be suitable
      to identify individual differences in glycation rates.

PMID- 16949516
TI  - Gastric emptying in patients with Type 2 diabetes mellitus and diabetes
      associated with mitochondrial DNA 3243 mutation using 13C-octanoic acid breath
      test.
AB  - Although the (13)C-octanoic acid breath test (OBT) has been applied to diabetic
      patients for assessing gastric emptying, such studies are still limited. Gastric
      emptying was measured using solid meal containing (13)C-octanoic acid in 52
      patients with Type 2 diabetes mellitus and 4 diabetic patients with mitochondrial
      DNA (mitDNA) 3243 mutation. Delayed gastric emptying was detected in 29% of
      patients with Type 2 diabetes mellitus, and multiple regression analysis showed
      that gastric emptying was independently associated with gastrointestinal symptoms
      and cardiac autonomic neuropathy. Gastric emptying was not related to gastric
      dysrhythmia in cutaneous electrogastrography (EGG). Diabetic patients with mitDNA
      3243 mutation showed delayed gastric emptying. Because the pathogenesis of
      delayed gastric emptying is multifactorial in diabetic patients, the recently
      developed OBT is useful for studying gastric emptying in various clinical
      settings of diabetic patients.

PMID- 16949517
TI  - Bone mineral density of both genders in Type 1 diabetes according to bone
      composition.
AB  - AIMS: This study is an investigation of the impact of Type 1 diabetes on bone
      mineral density (BMD) with regard to bone composition. MATERIAL AND METHODS:
      Thirty male and 30 premenopausal female patients with Type 1 diabetes (IDD) were
      retrospectively compared with an equal number of healthy individuals, matched on
      a person-to-person basis and to the reference population mean. BMD was measured
      at the L2-L4 vertebrae and femoral neck (FN) by dual energy X-ray absorptiometry
      (DXA). RESULTS: BMD absolute values were significantly lower in the diabetic than
      in the healthy males at vertebrae and FN (P<.05). The vertebral BMD values of
      diabetic women did not significantly differ, whereas those of FN were
      significantly lower compared with those of the healthy participants. FN age
      adjusted BMD values (Z scores) were significantly lower than those of the healthy
      persons and the population reference mean in both genders (P=.01, <.001 for males
      and <.01 for females), whereas regarding the vertebrae, only in the diabetic
      males (P<.05 and <.01 respectively). The percentages of osteopenia and
      osteoporosis were significantly higher in the male compared to the female
      diabetic patients (P<.001). No significant correlations existed between the BMD
      values and diabetes duration, glycosylated hemoglobin (HbA1c) concentration, or
      age of diabetes onset. Similar results were obtained when applying stepwise
      multiple regression analysis to explain the BMD value variance. CONCLUSIONS:
      Young males with Type 1 diabetes exhibit significantly lower BMD values of
      trabecular and mixed cortical-trabecular bone, compared with matched healthy
      persons. Premenopausal females with Type 1 diabetes present significantly lower
      BMD values of mixed bone only. Blood glucose control and diabetes duration do not
      appear to influence BMD behavior.

PMID- 16949518
TI  - Measuring the pain threshold and tolerance using electrical stimulation in
      patients with Type II diabetes mellitus.
AB  - OBJECTIVE: The aim of the study was to assess pain threshold and tolerance in
      diabetics with/without neuropathy and to compare that in with healthy controls.
      METHODS: In this cross-sectional and comparative study, 79 diabetics (57 without
      neuropathy and 22 with neuropathy) and 32 healthy controls (63 women and 48 men)
      with a mean age of 48.11+/-7.52 years were studied. Seventy-nine diabetics, aged
      33 to 74, who met inclusion criteria were evaluated using electrical stimulation
      (faradic current) to assess pain threshold and tolerance on upper and lower
      extremities and were compared with healthy controls. They also were evaluated
      using Michigan Neuropathy Screening Index (MNSI), 5.07 mmg Semmes Weinstein
      Monofilament, and visual analog scale (VAS). Pain threshold and tolerance were
      measured experimentally. RESULTS: Of all participants, 32.4% had pain complain.
      Eighteen diabetics without neuropathy (31.6%) and 9 diabetics with neuropathy
      (40.9%) reported pain. The result of upper and lower extremities' pain threshold
      and tolerance showed that there was a significant difference between diabetics
      and healthy participants (P<.05). Diabetics with neuropathy had the highest pain
      threshold and tolerance. The impairments in light touch sense were highest in
      diabetics with neuropathy (P<.05). CONCLUSION: Measuring pain threshold and
      tolerance of diabetic patients using electrical stimulation is an easy,
      noninvasive, cheap and repeatable method and can be used for defining the onset
      of diabetic neuropathy and controlling prognosis at early stage.

PMID- 16949519
TI  - A common variant in the ACE gene is associated with peripheral neuropathy in
      women with type 2 diabetes mellitus.
AB  - AIMS: The D allele of the ACE I/D gene variant is associated with higher tissue
      and serum ACE activity. Previously, studies have suggested an association between
      the D allele with the microvascular complications of diabetes. The aim of this
      study was to explore the impact of this genotype in relation to clinically
      manifest peripheral neuropathy (PN) in a cohort of subjects with type 2 diabetes
      mellitus (type 2 DM). METHODS: Five hundred and seventy-two Caucasian subjects
      (230 females, 342 males) with type 2 DM were recruited from the diabetes clinic
      at University College London Hospitals NHS Trust. Clinically manifest PN was
      determined from a standardized clinical examination. RESULTS: The ACE I/D
      genotype distribution was in Hardy-Weinberg equilibrium. In the whole group, no
      significant association was seen between genotype and PN; however, when
      stratified by sex, the D allele was associated with PN in females but not in
      males. The odds ratio (OR) for PN in the D allele carriers compared to those
      homozygous for the I allele was significantly higher in females [OR 2.93 (1.09
      7.63), P=.027] but not in males [OR 1.2 (0.61-2.36), P=.60]. CONCLUSIONS: The
      presence of the D allele is associated with increased risk of peripheral
      neuropathy in females but not in male subjects with type 2 DM, suggesting a role
      for the renin-angiotensin system in the development of PN.

PMID- 16949520
TI  - Association between PON 1 polymorphisms, PON activity and diabetes complications.
AB  - The paraoxonase (PON) gene cluster maps to human chromosome 7q21-22. In the PON 1
      gene, several polymorphisms in the promoter and coding regions have been
      identified and are known to influence gene expression levels. Promoter
      polymorphisms have been shown to have the strongest influence on paraoxonase
      activity levels. Paraoxonase, a high-density lipoprotein associated enzyme,
      protects lipoproteins from oxidation. Lipid oxidation may play an important role
      in the development of micro- and macrovascular disease. There is evidence that
      paraoxonase activity is reduced in patients with diabetes. We therefore
      hypothesise that PON 1genotypes influence paraoxonase activity levels and
      increase the risk of microvascular disease in type 1 diabetes. Genotyping of 156
      Caucasian adolescents with diabetes for seven PON 1 polymorphisms was performed,
      including that of a novel PON 1 promoter polymorphism A(-1074)G. PON genotypes
      were related to paraoxonase and arylesterase activities and diabetes complication
      status. There was strong linkage disequilibrium between the PON 1 promoter
      polymorphisms. Both promoter and coding region polymorphisms strongly influenced
      activity levels and were associated with diabetes complications. PON 1 genotypes
      Leu/Leu 54, AA(-162) and GG(-1074) were associated with higher urinary albumin
      loss, while the genotype GG(-907) was protective for retinopathy.

PMID- 16949521
TI  - Expression of matrix metalloproteinases and growth factors in diabetic foot
      wounds treated with a protease absorbent dressing.
AB  - Wound healing in diabetes is impaired, and nonhealing ulceration represent
      clinically relevant complications. Persistently high levels of matrix
      metalloproteases (MMPs) contribute to wound chronicity. Thus, the topical use of
      protease inhibitors might influence wound healing and promote transition from a
      chronic to an acute wound. METHODS: In this study, 33 patients with chronic
      diabetic foot lesions (stage 2a of the University of Texas Wound Classification
      system) were included. Fifteen patients received redundant "good standard wound
      care." In addition, 18 patients were treated with a protease inhibitory
      modulating matrix (the OCR/collagen Promogran matrix, Ethicon) with dressings
      changed on a daily basis. Prior to treatment and at 4 and 8 days after treatment,
      two 3-mm punch biopsies were taken from the center of the wounds and analyzed
      using ELISA techniques for MMPs, tissue inhibitor of MMP-2 (TIMP-2), and
      interleukin-1beta (IL-1beta) levels. In addition, mRNA levels of MMPs as well as
      IL-1beta and TNF-alpha were detected using quantitative real-time polymerase
      chain reaction (TaqMan, Applied Biosystems, Weiterstadt, Germany). RESULTS: No
      differences were detected between both groups and at the three time points for
      the mRNA levels of MMPs as well as of IL-1beta and TNF-alpha. In addition, MMP
      levels in wound tissue (analyzed by ELISA) were also not significantly different
      between both groups. However, IL-1beta was increased on day 8 in the treatment
      group (P=.01) only. Interestingly, we found a significant reduction of the MMP
      9/TIMP-2 ratio in the group being treated with the ORC/collagen. These wounds
      exhibited a more rapid healing rate when treated with the ORC/collagen matrix.
      CONCLUSIONS: The local treatment with a protease inhibitor has a beneficial
      effect on wound healing. In contrast to the data on wound fluid, our study
      demonstrated for the first time the unaltered mRNA levels of MMPs during
      treatment with a protease inhibitory modulating matrix. At the cellular level,
      MMPs were also not statistically different. However, the more relevant ratio of
      MMP-9/TIMP-2 was decreased in the treatment group. An equally important finding
      was that we did not detect a compensatory increase in the MMP-RNA expression even
      though wound size was clearly reduced.

PMID- 16949522
TI  - The thiazolidinedione drug troglitazone up-regulates nitric oxide synthase
      expression in vascular endothelial cells.
AB  - Endothelial dysfunction is a phenomenon often observed in diabetic patients,
      which is a cause for vascular complications of diabetes mellitus. Endothelium
      derived nitric oxide (NO) is responsible for vasodilatation, and NO-dependent
      vasodilatation is diminished in diabetic patients. In the present study, we
      evaluated the effects of thiazolidinediones (TZDs), antidiabetic drugs known to
      improve insulin resistance and to have vasodilating properties, on endothelial NO
      synthase (eNOS) expression in cultured vascular endothelial cells. Human
      umbilical vein endothelial cells were treated with the TZDs troglitazone and
      pioglitazone, or the peroxisome proliferator-activated receptor (PPAR) gamma
      activator 15-deoxy-Delta(12,14)-prostaglandin J(2) (15-dPGJ2). The expression of
      eNOS protein and its mRNA was determined by Western and Northern blot analyses,
      respectively. The effect of alpha-tocopherol that possesses structural similarity
      to troglitazone was also examined. Troglitazone up-regulated eNOS protein and its
      mRNA levels, whereas pioglitazone and 15-dPGJ2 failed to increase their levels.
      By contrast, alpha-tocopherol also increased in eNOS protein and mRNA. These
      results suggest that troglitazone up-regulates eNOS expression probably through
      its 6-hydroxychromanes structure but not activating PPARgamma.

PMID- 16949524
TI  - A bioabsorbable fixation implant for use in proximal interphalangeal joint
      (hammer toe) arthrodesis: Biomechanical testing in a synthetic bone substrate.
AB  - The surgical correction of hammer toe deformity of the lesser toes is one of the
      most commonly performed forefoot procedures. In general, percutaneous Kirschner
      wires are used to provide fixation to the resected proximal interphalangeal
      joint. Although these wires are effective, issues such as pin tract infections as
      well as difficult postoperative management by patients make alternative fixation
      methods desirable. This study biomechanically compared a threaded/barbed
      bioabsorbable fixation implant made of a copolymer of 82% poly-L-lactic acid and
      18% polyglycolic acid with a 1.57-mm Kirschner wire using the devices to fix 2
      synthetic bone blocks together. Constructs were evaluated by applying a
      cantilever load, which simulated a plantar force on the middle phalanx. In all
      cases, the failure mode was bending of the implant, with no devices fracturing.
      The stiffness (approximately 6-9 N/mm) and peak load (approximately 8-9 N) of the
      constructs using the 2 systems were equivalent. Accelerated aging at elevated
      temperature (47 degrees C) in a buffer solution showed that there was no
      reduction in mechanical properties of the bioabsorbable system after the
      equivalent of nearly 6 weeks in a simulated in vivo (37 degrees C) environment.
      These results suggest that the bioabsorbable implant would be a suitable fixation
      device for the hammer toe procedure.

PMID- 16949525
TI  - The below-the-ankle circular frame: A new technique for the treatment of
      displaced calcaneal fractures.

PMID- 16949526
TI  - Fracture dislocations of the tarsometatarsal joints: Analysis of interrater
      reliability in using the modified Hardcastle classification system.
AB  - Fracture dislocations/subluxations of the tarsometatarsal joint are complex
      injuries that are often misdiagnosed. Prompt recognition and treatment of
      Lisfranc injuries decrease the likelihood of long-term sequelae. The original
      (1909) classification system was modified in 1982 and again in 1986. The 1986
      classification system, developed by Hardcastle et al, is used most widely in
      clinical practice and is cited most often in the biomedical literature. For this
      or any-classification system to be beneficial, however, multiple observers must
      be able to use it in a consistent manner, and a high level of interrater
      agreement should exist. This study examined interrater reliability among
      clinicians using the modified Hardcastle classification system for Lisfranc
      fracture dislocations. Thirteen Lisfranc injury radiographs were evaluated by 21
      independent observers consisting of surgeons and residents (podiatric and
      orthopedic) as well as musculoskeletal radiologists, who classified radiographs
      according to the modified Hardcastle classification system. We used kappa
      statistics to evaluate the degree of interrater reliability for the entire group.
      A mean weighted kappa value of 0.54 was found for the group. Moderate interrater
      agreement was observed among clinicians interpreting the modified Hardcastle
      classification system for Lisfranc fracture dislocations.

PMID- 16949527
TI  - The usefulness of magnetic resonance imaging in the diagnosis of anterolateral
      impingement of the ankle.
AB  - The purpose of this study is to assess the sensitivity and specificity of
      magnetic resonance imaging (MRI) in the diagnosis of anterolateral impingement of
      the ankle and to assess the most helpful sequence in making the diagnosis. Twenty
      four patients who had undergone ankle arthroscopy were chosen. Twelve patients
      had arthroscopically documented anterolateral impingement, and 12 patients with
      no impingement on arthroscopy served as controls. Two musculoskeletal
      radiologists and an orthopedic surgeon, blinded to the operative diagnosis,
      retrospectively reviewed selective MRI images in the sagittal, axial, and coronal
      planes. The sensitivities and specificities were calculated for all 3 reviewers.
      The Kendall coefficient of concordance was calculated for overall agreement among
      reviewers. Sensitivities varied from 0.75 to 0.83, whereas specificities varied
      from 0.75 to 1.00. Using the Fisher exact test of contingency, the sensitivities
      and specificities showed that all reviewers' interpretations were statistically
      significant with P = .039, .001, and .012, respectively. The axial images were
      felt to be most helpful in making the diagnosis. The physicians felt that the
      sagittal images were helpful in 67%, 83%, and 100%, respectively. MRI is a useful
      tool that can aid the clinician in the diagnosis of anterolateral impingement of
      the ankle. T1 sagittal images demonstrating displacement of the normal fat signal
      anterior to the fibula by scar can be useful and help to confirm the diagnosis.

PMID- 16949528
TI  - Management of complex open fracture injuries of the midfoot with external
      fixation.
AB  - Ten patients (11 feet) with severe, high-velocity, open injuries to the midfoot
      were treated with uniplanar external fixation. The mean patient age was 38 years.
      Five wounds measured >10 cm, and 3 had extensive degloving of the foot extending
      into the lower leg. All had grossly comminuted fractures of the tarsal and
      metatarsal bones: 9 patients had a fractured cuboid; 6 had a fractured navicular;
      7 had a fractured cuneiform; and all had metatarsal fractures. Lisfranc joint
      dislocations were present in 7 feet, and intertarsal dislocations were seen in 3
      cases. Six patients underwent split-thickness skin grafting, and 1 required a
      myocutaneous flap. The average duration of fixator use was 9 weeks (range, 6-15
      weeks). Clinically, patients were evaluated 1 year after fixator removal for any
      residual pain in the foot, ability to stand on tiptoe, presence of a limp,
      deformity of an arch, and range of motion at the ankle, subtalar, and
      metatarsophalangeal joints. Each parameter was graded as good, fair, or poor. All
      patients had sensate plantigrade feet, with 2 patients who experienced pain on
      weight bearing, 5 who had difficulty standing comfortably on tiptoe, and 2 who
      limped because of pain. Three patients exhibited flatfoot deformity, whereas 4
      had cavus deformity. All demonstrated stiffness at the midfoot and restriction of
      subtalar and forefoot motion, with 5 also having restricted ankle motion.
      Radiographically, all fractures were healed at the time of follow-up; 4 were
      malunited, with 1 demonstrating ankylosis across the tarsometatarsal joint. These
      results suggest that crush injuries to the midfoot often result in persistent
      morbidity despite early comprehensive management with external fixation.

PMID- 16949529
TI  - Hydroxyapatite augmentation for bone atrophy in total ankle replacement in
      rheumatoid arthritis.
AB  - Although total ankle replacement is routinely used for rheumatoid arthritis of
      the ankle, it has been hampered by early implant failures such as loosening and
      subsidence of the tibial component due to poor bone quality. To prevent this
      complication, total ankle replacement augmented by a specially designed
      hydroxyapatite coating was used in 14 patients (16 feet). Patients were reviewed
      after an average follow-up of 23.1 months, and the mean clinical rating scale
      significantly improved from 30.7/100 points preoperatively to 65.9/100 at final
      follow-up, especially with respect to pain relief. Radiographs taken immediately
      postoperatively and at final follow-up were analyzed for the position and sinking
      of the tibial component. The position was evaluated by measurement of the alpha
      and beta angles, formed by the tibial long axis and tibial component on
      anteroposterior and lateral radiographs, respectively. The mean alpha and beta
      angles were 87.4 degrees and 79.3 degrees postoperatively and 87.7 degrees and
      81.0 degrees at final follow-up, respectively. No significant change was noted in
      either angle between the immediate postoperative views and at final follow-up,
      and no significant subsidence was noted. Radiographs were also assessed for the
      presence of a lucent zone: 1 case demonstrated a clear zone between
      hydroxyapatite and bone, 9 cases between hydroxyapatite and the tibial component,
      and 6 cases between the tibial component and bone. These results suggest that
      hydroxyapatite helps to secure implant fixation firmly to the bone, making it a
      useful augmentation for tibial bone atrophy in total ankle replacement for
      rheumatoid arthritis.

PMID- 16949530
TI  - The use of nanocrystalline hydroxyapatite for the reconstruction of calcaneal
      fractures: Preliminary results.
AB  - The purpose of this investigation was to evaluate the feasibility of a
      nanocrystalline hydroxyapatite compound in the treatment of calcaneal fractures
      with osseous defects after reduction. The study included 21 patients,
      representing 24 closed intraarticular calcaneus fractures with large defects
      remaining after operative reduction. All cases were supplemented with the
      hydroxyapatite bone substitute and stabilized with a calcaneal honeycomb plate.
      Radiographs were taken at 6 weeks, 12 weeks, 6 months, and 1 year
      postoperatively, with specific attention given to measurement of Gissane's angle,
      Bohler's angle, and calcaneal height. A postoperative subjective and objective
      evaluation of the fracture, using the Creighton Nebraska Health Foundation scale,
      was performed 1 year postoperatively. Bohler's angle improved from a mean 8.6 +/-
      5.3 degrees preoperatively to an immediate postoperative mean result of 31.5 +/-
      6.5 degrees and 27.7 +/- 8.6 1 year postoperatively. The mean Creighton-Nebraska
      functional score was 86 +/- 10 at the 1-year follow-up evaluation. These results
      suggest that open reduction with plate fixation combined with nanocrystalline
      hydroxyapatite augmentation presents a good and reliable surgical technique for
      treatment of calcaneus fractures.

PMID- 16949531
TI  - Pigmented villonodular synovitis of the foot and ankle: Forty years of experience
      from the Scottish bone tumor registry.
AB  - Fourteen cases of pigmented villonodular synovitis (PVNS) of the foot and ankle
      accrued from the Scottish Bone Tumor Registry are presented with an average
      follow-up of 4.6 years. This study analyzed the clinical, radiological, and
      histopathological features and investigated their clinical behavior and the
      factors influencing recurrence. The mean age of the patients was 26.4 years
      (range, 8-52 years). There were 8 women and 6 men. The mean delay in presentation
      was 10.3 months. The anatomical sites were phalanges (n = 2), tarso-metatarsal
      area (n = 3), and hindfoot (n = 9) (6 extraarticular soft tissue swellings around
      the ankle, 2 ankle, 1 subtalar joint). Eight (57.1%) cases presented with a
      painless lump, 5 (35.7%) patients had painful masses, and 1 case had a lump
      associated with toe deformity. Peri-articular tissue invasion and cortical
      infiltration were found in one third on plain films. Magnetic resonance imaging
      findings were suggestive of synovial sarcoma in 2 cases because of extensive low
      signal soft tissue hypertrophy and bone erosion. Excision of the lump was
      performed in 4 cases with a complete recovery. Phalangeal lesions were treated
      with toe amputation through the metatarsophalangeal joint, and no cases had
      recurrence. There were 2 recurrences affecting the ankle and the subtalar joint.
      There was a 14.3% recurrence rate, while complete recovery was achieved in 85.7%
      cases (12/14). A high index of suspicion for PVNS should be observed for cases
      presenting with a painless or painful mass in the foot and ankle region. Complete
      recovery can be achieved in the majority by complete excision. Toe amputation may
      be considered for foot phalangeal PVNS.

PMID- 16949532
TI  - Treatment of relapsed idiopathic clubfoot by complete subtalar release combined
      with the Ilizarov method.
AB  - This study presents the clinical and radiographic outcomes of 6 feet (4 patients)
      with relapsed idiopathic clubfoot that were treated with a combination of
      subtalar release and the Ilizarov method. The mean patient age at the time of the
      surgery was 7.4 years (range, 4.5-10.5 years), and the mean follow-up was 5.1
      years (range, 2.0-7.3 years). All cases achieved a plantigrade foot, better
      walking ability, and parental satisfaction with the result. Ankle joint range of
      motion increased from a mean of 17 degrees (range, 10-30 degrees) preoperatively
      to 45 degrees (range, 35-65 degrees) at final follow-up. The talocalcaneal angle
      improved from a mean of 26 degrees (range, 15-34 degrees) preoperatively to 55
      degrees (range, 47-65 degrees) at follow-up. The mean tibiocalcaneal angle
      improved from 95 degrees (range, 87-115 degrees) preoperatively to 80 degrees (77
      83 degrees) at follow-up, whereas the talometatarsal angle improved from a
      preoperative mean of -19 degrees (range, -35 to -10 degrees) to 3.5 degrees
      (range, -5 to 7 degrees) at follow-up. Recurrence was observed in only 1 foot
      with forefoot adductus, caused by a pin tract infection and early fixator
      removal. These cases suggest the Ilizarov method combined with subtalar release
      are beneficial for the treatment of relapsed idiopathic clubfoot.

PMID- 16949533
TI  - Pediatric longitudinal epiphyseal bracket: Review and case presentation.
AB  - The longitudinal epiphyseal bracket is a rare deformity affecting the long and
      short bones of the hands and feet, creating an aberration in growth. The
      deformity is present in 2% to 14% of congenital hand and foot deformities, with
      11% of all cases found in the great toe. Ultrasound may then be used to confirm
      the diagnosis. Radiographs usually show the presence of a bracket epiphysis once
      there is some ossification, but until then, the radiographs can appear normal.
      With the use of ultrasound, a suspected preossified bracket can be visualized and
      can establish the diagnosis. The purpose of this article is to present such a
      case with a preossified epiphyseal bracket of the great toe. The child presented
      initially with unremarkable x-rays, but the diagnosis was made with clinical
      suspicion and use of ultrasound. After surgical resection of the brackets, there
      was progressive improvement in the short-term follow-up. Long-term follow-up is
      essential until skeletal maturity, and, if the deformity persists, further
      surgical care may need to be implemented.

PMID- 16949534
TI  - Medial and lateral rotatory dislocations of the ankle after trivial trauma-
      pathomechanics and management of two cases.
AB  - Pure frontal plane rotatory dislocation of the ankle joint without an associated
      fracture is an extremely rare injury. We report one such case of an eversion
      rotatory dislocation and one case of an inversion rotatory dislocation. To our
      knowledge, this is the first report of an eversion injury resulting in
      dislocation of the ankle without fracture. Both patients had low energy trauma,
      predisposing ligamentous injuries, and recurrent sprains. In the patient with
      lateral rotatory dislocation, medial malleolar hypoplasia was also a contributing
      factor. Both patients healed the presenting index injury with nonoperative
      treatment, whereas the lateral rotatory dislocation had a lateral ankle
      stabilization to prevent subsequent injury.

PMID- 16949535
TI  - Reconstruction of a neglected achilles tendon rupture with an achilles tendon
      allograft: A case report.
AB  - Multiple surgical techniques for repair of neglected Achilles tendon ruptures
      have been described in the literature. The authors present a case using a freeze
      dried Achilles tendon allograft for repair of a neglected rupture of the Achilles
      tendon with a defect of 10 cm. At 1-year follow-up, the patient achieved pre
      injury functional use of the affected limb.

PMID- 16949536
TI  - Comparative vapour phase FTIR spectra and vibrational assignment of manganese
      pentacarbonyls derivatives of the type XMn(CO)5: (where X=Br, Cl, I, H, D, CH3,
      CD3, CF3).
AB  - The infrared spectra of pure Mn(CO)(5)X in the region 4000-400 cm(-1) has been
      obtained in the vapour phase. The observed spectrum has been analyzed to
      distinguish the fundamental frequencies, the rotational-vibrational and
      structure, and overtone and combination frequencies. The assignment of the
      observed vapour phase frequencies to the fundamental modes of vibration has been
      made on C(4V) symmetry. The weak peaks due to XMn(CO)(4)((13)CO) molecules have
      been measured and assigned for all molecules. This study provides a comprehensive
      comparison of these compounds, with all of these data the assignment of
      frequencies is reviewed and a set of quite unambiguous assignments made. The
      significant finding in this regards are that, it is not necessary to assume lower
      than C(4V) symmetry for XMn(CO)(5) as has been done in previous consideration of
      some infrared spectrum of these compounds.

PMID- 16949537
TI  - Statistical adjustment for misclassification of seat belt and alcohol use in the
      analysis of motor vehicle accident data.
AB  - The use of seat belts and alcohol is often mis-reported in police motor vehicle
      accident reports for a number of reasons. To avoid penalties, occupants often
      over report seat belt use and under report alcohol use. Police officers sometimes
      fail to account for evidence such as presence of belt burn, condition of belts,
      odor of alcohol, crash patterns, etc. Biased conclusions result when using
      misclassified accident data to estimate the effectiveness of seat belts in
      preventing injuries and reducing medical costs. We investigated the effects of
      misclassification of seat belt and alcohol use on the odds ratio of injury as
      well as medical costs. A statistical method and a SAS program were developed to
      adjust odds ratios of injury and medical cost estimates to account for
      misclassification of seat belts and alcohol use. The method allowed for
      incorporation of variables that could affect misclassification of seat belt and
      alcohol use. We conducted a Monte Carlo simulation and found that when there were
      large differences between the misclassification rates for major and minor injury,
      the unadjusted odds ratio could have up to a 90% bias while our adjusted odds
      ratio was effectively unbiased. To illustrate the method, we estimated the
      misclassification rates of seat belt and alcohol use by comparing merged police
      and hospital reports from Nebraska motor vehicle accident data sets (1996-1997)
      and then evaluated the bias of the odds ratio of injury and medical costs
      estimates due to misclassification. Our results showed that the bias of the odds
      ratio of injury and medical costs due to misclassification of seat belts and
      alcohol use depended both on the amount of misclassification and the reported
      frequencies. Misclassification about seat belt and alcohol use only slightly
      biased the unadjusted odds ratio estimates and mean hospital charge, while
      misclassification resulted in approximately a 69% underestimate of the total
      medical costs savings due to seatbelts. However, due to the small size of the
      merged Nebraska police and hospital data set used to estimate misclassification
      rates, these results are likely somewhat imprecise.

PMID- 16949538
TI  - Comparative judgments with missing information: a regression and process tracing
      analysis.
AB  - We had participants decide which one of two applicants was better qualified for a
      scholarship. They also judged the difference between them (comparative judgment).
      The applicants were described by features (grades) in different subjects
      (dimensions). The grades on some dimensions were missing (unique dimensions) for
      an alternative while all the grades were available on other dimensions (common
      dimensions). In a conventional regression analysis, we found that decision makers
      gave more weight to dimensions when they were common than when they were unique.
      However, this commensurability effect was limited to medium important dimensions
      and did not apply to dimensions of high or low importance. We also observed how
      participants retrieved information for the choice alternatives and analysed how
      importance and commensurability are reflected in the processing prior to the
      decision. Features on more important or common dimensions were inspected earlier
      than features on less important or unique dimensions. Participants preferred
      dimensional transitions and inspected features on unique dimensions longer than
      their common counterparts. This finding suggested that participants used
      inferences when features were missing. We propose an outline of a decision
      heuristic to describe decision making with missing information.

PMID- 16949539
TI  - A quantitative electrochemiluminescence assay for Clostridium perfringens alpha
      toxin.
AB  - Described is a rapid direct sandwich format electrochemiluminescence assay for
      identifying and assaying Clostridium perfringens alpha toxin. Biotinylated
      antibodies to C. perfringens alpha toxin bound to streptavidin paramagnetic beads
      specifically immunoadsorbed soluble sample alpha toxin which subsequently
      selectively immunoadsorbed ruthenium (Ru)-labeled detection antibodies. The
      ruthenium chelate of detection antibodies chemically reacted in the presence of
      tripropylamine and upon electronic stimulation emitted photons
      (electrochemiluminescence) that were detected by the photodiode of the detector.
      Elevated toxin concentrations increased toxin immunoadsorption and the specific
      immunoadsorption of Ru-labeled antibodies to alpha toxin, which resulted in
      increased dose-dependent electrochemiluminescent signals. The standardized assay
      was rapid (single 2.5-h coincubation of all reagents), required no wash steps,
      and had a sensitivity of about 1 ng/ml of toxin. The assay had excellent accuracy
      and precision and was validated in buffer, serum, and urine with no apparent
      matrix effects.

PMID- 16949540
TI  - The photosynthetic deficiency due to puhC gene deletion in Rhodobacter capsulatus
      suggests a PuhC protein-dependent process of RC/LH1/PufX complex reorganization.
AB  - Optimal photosynthetic reaction centre (RC) and core antenna (LH1) levels in the
      purple bacterium Rhodobacter capsulatus require the puhC gene. Deletion of puhC
      had little effect on RC and LH1 assembly individually, but significantly
      inhibited the photosynthetic growth of RC+ LH1- strains, suggesting that maximal
      RC catalytic activity is PuhC-dependent. Consistent with post-assembly
      reorganization of the RC/LH1/PufX core complex by PuhC to include latecomer
      proteins, spatial separation of pufX from the RC/LH1 genes inhibited PufX
      accumulation and photosynthetic growth only in PuhC- strains. Photosynthetic
      activity improved to different degrees when PuhC homologues from three other
      species were expressed in PuhC- R. capsulatus, indicating that PuhC homologues
      function similarly but may interact inefficiently with a heterologous core
      complex. Anaerobic photosynthetic growth of PuhC- strains was affected by the
      duration of prior semiaerobic growth, and by two genes that modulate
      bacteriochlorophyll production: pufQ and puhE. These observations agree with a
      speculative model in which reorganization of the core complex is an important
      regenerative process, accelerated by PuhC.

PMID- 16949541
TI  - Quantification of Mg2+ extrusion and cytosolic Mg2+-buffering in Xenopus oocytes.
AB  - Intracellular Mg(2+) buffering and Mg(2+) extrusion were investigated in Xenopus
      laevis oocytes. Mg(2+) or EDTA were pressure injected and the resulting changes
      in the intracellular Mg(2+) concentration were measured simultaneously with
      Mg(2+)-selective microelectrodes. In the presence of extracellular Na(+),
      injected Mg(2+) was extruded from the oocytes with an estimated v(max) and K(M)
      of 74 pmol cm(-2)s(-1) and 1.28 mM, respectively. To investigate genuine
      cytosolic Mg(2+) buffering, measurements were carried out in the nominal absence
      of extracellular Na(+) to block Mg(2+) extrusion, and during the application of
      CCCP (inhibiting mitochondrial uptake). Under these conditions, Mg(2+) buffering
      calculated after both MgCl(2) and EDTA injections could be described by a buffer
      equivalent with a concentration of 9.8mM and an apparent dissociation constant,
      K(d-app), of 0.6mM together with an [ATP](i) of 0.9 mM with a K(d-app) 0.12 mM.
      Xenopus oocytes thus possess highly efficient mechanisms to maintain their
      intracellular Mg(2+) concentration.

PMID- 16949542
TI  - Activity coupling of Vibrio harveyi luciferase and flavin reductase (FRP): oxygen
      as a probe.
AB  - Several lines of evidence have been reported previously to document the ability
      of the Vibrio harveyi NADPH-specific flavin reductase FRP to directly transfer
      reduced riboflavin-5'-phosphate to luciferase for bioluminescence. This study
      aimed at characterizing further the kinetic properties of FRP in such a direct
      channeling system and investigating whether the complete direct transfer of
      reduced flavin was the exclusive pathway in the FRP:luciferase coupled
      bioluminescence reaction. To these ends, a new kinetic approach of oxygen
      variation was employed. Results indicated that increases in oxygen concentration
      led to gradual decreases of the peak bioluminescence intensity, K(m,FMN), and
      K(m,NADPH) of FRP in the coupled reaction. In comparison with theoretical
      schemes, these findings indicated that the FRP:luciferase coupled reaction can
      utilize reduced flavin by both free diffusion and direct transfer. The upper
      limits of the true K(m,FMN) and K(m,NADPH) of FRP in the direct transfer system
      were determined.

PMID- 16949544
TI  - Identification of human UDP-glucuronosyltransferase isoform(s) responsible for
      the C-glucuronidation of phenylbutazone.
AB  - Glucuronidation is a major metabolic pathway in the biotransformation of many
      xenobiotics and endogeneous compounds. There have been many studies on the
      formation of O-, N- or S-glucuronides and identification of the UDP
      glucuronosyltransferase (UGT) isoforms responsible for the formation of these
      glucuronides. However, there is no information available on which UGT isoform(s)
      catalyzes C-glucuronidation. In the present study, 16 human UGTs (UGTs 1A1, 1A3,
      1A4, 1A5, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B10, 2B11, 2B15, 2B17 and 2B28)
      were cloned and expressed in baculovirus-infected insect cells and investigated
      to determine their C-glucuronidating activity toward phenylbutazone (PB). Among
      the UGT isoforms investigated, only UGT1A9 catalyzed PB C-glucuronidation. Human
      liver and kidney microsomes, which are well known to express UGT1A9, had C
      glucuronidating activity toward PB. However, the jejunum, which did not express
      UGT1A9, had no C-glucuronidating activity. These results demonstrate for the
      first time that PB C-glucuronidation is catalyzed by only UGT1A9.

PMID- 16949543
TI  - Multiple co-activator complexes support ligand-induced transactivation function
      of VDR.
AB  - Vitamin D receptor (VDR) mediates a wide variety of vitamin D actions through
      transcriptional controls of target genes as a ligand-dependent transcription
      factor. The transactivation by VDR is known to associate with two co-activator
      complexes, DRIP/TRAP and p160/CBP, through physical interaction with DRIP205 and
      p160 members (TIF2) components, respectively. However, functional difference
      between the two co-activator complexes for VDR co-activation remains unclear. In
      the present study, to address this issue, a series of point mutants in VDR helix
      12 were generated to test the functional association. Alanine replacement of VDR
      valine 418 resulted in loss of DRIP205 interaction, but it was still
      transcriptionally potent with ability to interact with TIF2. Surprisingly, the
      V421A mutant was only partially impaired in transactivation without co-activator
      interaction, implying presence of a putative co-activator/complex. Thus, these
      findings suggest that ligand-induced transcriptional controls by VDR require a
      number of known and unknown co-regulator complexes, that may support the tissue
      specific function of VDR.

PMID- 16949545
TI  - Rosemary (Rosmarinus officinalis) diterpenes affect lipid polymorphism and
      fluidity in phospholipid membranes.
AB  - Rosemary (Rosmarinus officinalis) extracts are widely used in the food,
      nutraceutical and cosmetic areas. Their major bioactive components have shown
      antioxidant, antimicrobial, anti-inflammatory, antitumorigenic and
      chemopreventive activities. In this work, the bioactive compounds deriving from
      rosemary leaves (carnosol, CAR; carnosic acid, CA; rosmadial, RAL; genkwanin, GW;
      rosmarinic acid, RA) were isolated and their effects on the phase behaviour of
      model membranes were studied by several complementary biophysical techniques. All
      diterpenes studied, and specifically CAR, decreased the hydrophobic interactions
      between acyl chains, as well as broadened and shifted the phospholipid transition
      to lower temperatures into dimyristoylphosphatidylcholine (DMPC) membranes. In
      addition, all diterpenes and genkwanin increased the lipid order of fluid DMPC
      membranes, exhibiting CAR and RAL the strongest membrane-rigidifying effect. The
      diterpenoids, especially CA and RAL, promoted the formation of hexagonal-H(II)
      phases at low temperatures in dielaidoylphosphatidylethanolamine (DEPE) membranes
      which exhibited a smaller tube-to-tube distance compared to pure phospholipid.
      These diterpenes were also able of promoting isotropic structures in DEPE
      membranes which consisted of non-periodically ordered lipid structures as
      demonstrated by X-ray diffraction. In contrast, minor effects were observed by
      rosmarinic acid. In conclusion, diterpenes and genkwanin from rosemary show
      membrane-rigidifying effects which may contribute to their antioxidant capacity
      through hindering diffusion of free radicals.

PMID- 16949546
TI  - Structure and properties of K141E mutant of small heat shock protein HSP22
      (HspB8, H11) that is expressed in human neuromuscular disorders.
AB  - Some properties of the K141E mutant of human HSP22 that is expressed in distal
      hereditary motor neuropathy were investigated. This mutation slightly decreased
      intrinsic fluorescence of HSP22 and induced changes in the far UV CD spectra that
      correlate with increase of disordered structure. Destabilized K141E mutant was
      more susceptible to trypsinolysis than the wild type protein. Mutation K141E did
      not significantly affect the hydrophobic properties measured by bis-ANS binding
      and did not affect the quaternary structure of HSP22. With insulin as a substrate
      the chaperone-like activity of K141E mutant and the wild type protein were
      similar. However with alcohol dehydrogenase and rhodanese the chaperone-like
      activity of K141E mutant was remarkably lower than the corresponding activity of
      the wild type protein. It is concluded that K141E mutation induces
      destabilization of HSP22 structure and probably by this means diminish the
      chaperone-like activity of HSP22 with certain protein substrates.

PMID- 16949548
TI  - Regulation of magnesium homeostasis and transport in mammalian cells.
AB  - Magnesium is the second most abundant cation within the cell after potassium and
      plays an important role in numerous biological functions. Several pieces of
      experimental evidence indicate that mammalian cells tightly regulate Mg(2+)
      content by precise control mechanisms operating at the level of Mg(2+) entry and
      efflux across the cell membrane, as well as at the level of intracellular Mg(2+)
      buffering and organelle compartmentation under resting conditions and following
      hormonal stimuli. This review will attempt to elucidate the mechanisms involved
      in hormonal-mediated Mg(2+) extrusion and accumulation, as well as the
      physiological implications of changes in cellular Mg(2+) content following
      hormonal stimuli.

PMID- 16949547
TI  - Studies on titin PEVK peptides and their interaction.
AB  - Experiments were conducted on several synthetic and expressed peptides from the
      PEVK region of titin, the giant muscle protein. Different secondary structure
      prediction methods based on amino acid sequence gave estimates ranging from over
      70% alpha helical to no helix (totally disordered) for the polyE peptide
      corresponding to human exon 115. Circular dichroism (CD) experiments demonstrated
      that both the positively charged PPAK modules and the negatively charged PolyE
      repeats had similar spectral properties with disordered secondary structure
      predominating. Gel permeation chromatography showed that both PPAK and polyE
      peptides had 2-4 times larger Stokes radii than expected from their molecular
      mass. Mixtures of the oppositely charged titin peptides caused no change in
      apparent secondary structure as observed by circular dichroism or migration
      properties using native gel electrophoresis. Similarly addition of calcium did
      not alter the CD spectra or peptide electrophoretic mobility of the individual
      peptides or their mixtures. The properties of both the PPAK and polyE type
      peptides suggest that both had most of the characteristic properties to be
      classified as intrinsically disordered proteins.

PMID- 16949549
TI  - Effect of diastolic pressure on MLC2v phosphorylation in the rat left ventricle.
AB  - The effect of passive muscle stretch on the extent of MLC2v phosphorylation was
      investigated. We used an isolated rat heart preparation and controlled the
      passive pressure of the left ventricle (LV) at 0 or 15 mmHg. The hearts were
      flash frozen and the LV free wall was split into epicardial and the endocardial
      halves. The samples were solubilized using a novel method that minimizes changes
      in the phosphate content of MLC2v under non-denaturing conditions. The proteins
      were separated by urea glycerol PAGE and identified by mass spectrometry and
      Western blots. At 0 mmHg passive pressure, the extent of MLC2v phosphorylation of
      the epicardium (34.1+/-1.7%) was the same as that of the endocardium (35.3+/
      3.4%). At 15 mmHg passive pressure, we found a significant increase in MLC2v
      phosphorylation in the epicardium (to 41.5+/-2.0%) and a significant reduction in
      the endocardium (to 24.2+/-1.2%), giving rise to a gradient in the extent of
      MLC2v phosphorylation from epicardium (high) to endocardium (low). These changes
      in MLC2v phosphorylation that take place in response to increased diastolic
      pressure are likely to impact on the calcium sensitivity of actomyosin
      interaction (with an increased sensitivity towards the epicardium) and may play a
      role in the Frank-Starling mechanism of the heart.

PMID- 16949550
TI  - A folding pattern that is stable to thermal cycling is achieved by long term
      storage of recombinant human beta-casein with four extra N-terminals amino-acid
      residues at -20 degrees C.
AB  - Studies have followed the turbidity (OD400 nm) of beta-casein (CN) as temperature
      (T) increased from 4 to 37 degrees C. Native non-phosphorylated beta-CN showed a
      turbidity increase above 25 degrees C and precipitated at about 22 degrees C in
      5mM Ca+2. These patterns were reproducible upon T-cycling while those of
      recombinant beta-CN proteins are not. Here, a wild-type recombinant that was
      thermally stable after being frozen in solution and stored at -20 degrees C for a
      prolonged period of time was denatured with guanidine HCl and refolded by
      dialysis against buffer. This protein was again not stable to T-cycling. A
      recombinant mutant with four extra N-terminal amino acids was very stable to T
      cycling, both with and without 5mM Ca+2. However, it was still much different
      than the native protein. These results indicate that there are probably many
      energy minima for this protein and emphasize the possibility of "chaperon-like"
      conditions for proper folding of human beta-CN.

PMID- 16949551
TI  - Fluorescence labeling and computational analysis of the strut of myosin's 50kDa
      cleft.
AB  - A new fluorescent labeling procedure specific for the strut sequence of myosin
      subfragment-1's 50kDa cleft was developed using CY3 N-hydroxy succinimidyl ester
      as a hydrophobic tag and hydrophobic interaction chromatography to purify the
      major labeled species which retained actin-activated ATPase activity. Stern
      Volmer analysis suggests that the CY3 is in close proximity to basic residues,
      consistent with inspection of the mapped labeling site in the atomic model.
      Fluorescence polarization indicates that the CY3 becomes more mobile upon actin
      binding, supporting a location near the actomyosin interface. In contrast,
      nucleotide binding to myosin had little impact on the CY3. Molecular mechanics
      and stochastic dynamics simulations suggest that this labeling site is sensitive
      to forced cleft opening and closure, but the upper 50kDa cleft does not move
      easily. In addition, there appear to be some long-range effects of forced cleft
      opening and closing that could impact the lever arm position.

PMID- 16949552
TI  - Modulation of Kir4.2 rectification properties and pHi-sensitive run-down by
      association with Kir5.1.
AB  - Inwardly rectifying K+ channels (Kir) comprise seven subfamilies that can be
      subdivided further on the basis of cytosolic pH (pHi) sensitivity, rectification
      strength and kinetics, and resistance to run-down. Although distinct residues
      within each channel subunit define these properties, heteromeric association with
      other Kir subunits can modulate them. We identified such an effect in the wild
      type forms of Kir4.2 and Kir5.1 and used this to further understand how the
      functional properties of Kir channels relate to their structures. Kir4.2 and a
      Kir4.2-Kir5.1 fusion protein were expressed in HEK293 cells. Inward currents from
      Kir4.2 were stable over 10 min and pHi-insensitive (pH 6 to 8). Conversely,
      currents from Kir4.2-Kir5.1 exhibited a pHi-sensitive run-down at slightly acidic
      pHi. At pHi 7.2, currents in response to voltage steps positive to EK were
      essentially time independent for Kir4.2 indicating rapid block by Mg2+.
      Coexpression with Kir5.1 significantly increased the blocking time constant, and
      increased steady-state outward current characteristic of weak rectifiers.
      Recovery from blockade at negative potentials was voltage dependent and 2 to 10
      times slower in the homomeric channel. These results show that Kir5.1 converts
      Kir4.2 from a strong to a weak rectifier, rendering it sensitive to pHi, and
      suggesting that Kir5.1 plays a role in fine-tuning Kir4.2 activity.

PMID- 16949553
TI  - FTIR analysis of the interaction of arbutin with dimyristoyl phosphatidylcholine
      in anhydrous and hydrated states.
AB  - In this paper, the interaction of arbutin with dimyristoylphosphatidylcholine
      bilayers was studied by FTIR spectrometry. The results show that arbutin
      interacts in different extents with the phosphate and carbonyl groups of
      membranes in the gel state, the liquid crystalline state or subjected to osmotic
      stress. The effect, in the presence of water, on the antisymmetric stretching of
      the phosphate groups is qualitatively similar to that found with other molecules
      composed by a glucose moiety such as trehalose and sucrose. However, significant
      differences were found between these compounds and arbutin in the carbonyl
      region. Arbutin displaces the PO2- antisymmetric stretching to lower frequencies
      in lipids dispersed in water. This indicates strong hydrogen bonding. In
      contrast, in the solid state, this frequency increases. The effect on the
      carbonyl groups varies depending on the hydration state of the bilayer, which is
      achieved by changing the phase state of the bilayer or by osmotic stress. The
      hydrocarbon region is not affected by arbutin in the excess of water. However,
      symmetric and antisymmetric stretching of CH2 and CH3 are strongly affected in
      the dry state.

PMID- 16949554
TI  - Night-time thoughts in high and low worriers: reaction to caffeine-induced
      sleeplessness.
AB  - There is ample evidence for the existence of an association between sleeplessness
      and worry. Not much is known, however, concerning the nature of this
      relationship. Therefore, a study was conducted investigating the causal
      relationship between sleeplessness and nocturnal worry. A 2 x 2 (Worry x Induced
      sleeplessness) analysis of covariance design was used. The first factor consisted
      of a subject variable defined by scoring either high or low on a trait measure of
      worry (the Penn State Worry Questionnaire) and the second factor consisted of 300
      mg caffeine or placebo. A total of 96 female undergraduate students participated.
      The dependent variables comprised measures of nocturnal worry (the Night-Time
      Thoughts Questionnaire) and subjective and objective sleep parameters. Overall,
      caffeine caused an increase in nocturnal worry and sleeplessness. A significant
      interaction effect occurred between Worry and Induced sleeplessness on one of the
      objective sleep parameters, but no other interaction effects were significant.
      The results suggest that worry may occur as an epiphenomenon of sleeplessness.

PMID- 16949555
TI  - Participation of proteasome-associating complex PC500 in starfish oocyte
      maturation as revealed by monoclonal antibodies.
AB  - We previously reported that immature starfish oocytes contain a novel 530-kDa
      proteasome-associating complex PC500 [previously named PC530; E. Tanaka, M.
      Takagi Sawada, C. Morinaga, H. Yokosawa, H. Sawada, Isolation and
      characterization of a novel 530-kDa protein complex (PC 530) capable of
      associating with the 20S proteasome from star fish oocytes, Arch. Biochem.
      Biophys. 374 (2000) 181-188]. In the present study, in order to obtain an insight
      into the biological function of this complex, we investigated the effects of anti
      PC500 monoclonal antibodies on oocyte maturation of the starfish Asterina
      pectinifera. A monoclonal antibody 7C5 strongly inhibited germinal vesicle
      breakdown (GVBD) in a concentration-dependent manner. In contrast to the
      inhibitory effect of the 7C5 antibody on GVBD, no inhibition of egg cleavage was
      observed in a 7C5-antibody-microinjected single blastomere in a 2-cell stage
      embryo. These results indicate that PC500 plays a key role in starfish oocyte
      maturation in a meiosis-specific manner.

PMID- 16949556
TI  - Acacetin suppressed LPS-induced up-expression of iNOS and COX-2 in murine
      macrophages and TPA-induced tumor promotion in mice.
AB  - Acacetin (5,7-dihydroxy-4'-methoxyflavone), a flavonoid compound, has anti
      peroxidative and anti-inflammatory effects. In this study, we investigated the
      inhibitory effects of acacetin and a related compound, wogonin, on the induction
      of NO synthase (NOS) and COX-2 in RAW 264.7 cells activated with
      lipopolysaccharide (LPS). Acacetin markedly and actively inhibited the
      transcriptional activation of iNOS and COX-2. Western blotting, reverse
      transcription-polymerase chain reaction (PCR), and real-time PCR analyses
      demonstrated that acacetin significantly blocked protein and mRNA expression of
      iNOS and COX-2 in LPS-inducted macrophages. Treatment with acacetin reduced
      translocation of nuclear factor-kappa B (NF kappa B) subunit and the dependent
      transcriptional activity of NF kappa B. The activation of NF kappa B was
      inhibited by prevention of the degradation of inhibitor kappa B (I kappa B).
      Furthermore, acacetin inhibited LPS-induced phosphorylation as well as
      degradation of I kappa B alpha. We further investigated the roles of tyrosine
      kinase, phosphatidylinositiol 3-kinase (PI3K)/Akt and mitogen-activated protein
      kinase (MAPK) in LPS-induced macrophages. We found that acacetin also inhibited
      LPS-induced activation of PI3K/Akt and p44/42, but not p38 MAPK. After initiation
      of 7,12-dimethlybene[a]anthracene (DMBA), applying acacentin topically before
      each 12-O-tetradecanoylphorbol 13-acetat (TPA) treatment was found to reduce the
      number of papillomas at 20 weeks. Taken together, these results show that
      acacetin down regulates inflammatory iNOS and COX-2 gene expression in
      macrophages by inhibiting the activation of NF kappa B by interfering with the
      activation PI3K/Akt/IKK and MAPK, suggesting that acacetin is a functionally
      novel agent capable of preventing inflammation-associated tumorigenesis.

PMID- 16949557
TI  - Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells.
AB  - Exposure to nicotine has a broad range of physiological and psychological effects
      that can be long lasting and contribute to nicotine dependence. On a time course
      longer than that needed to activate nicotinic acetylcholine receptor (nAChR)
      function, nicotine exposure induces functional inactivation of nAChR,
      upregulation of nAChR radioligand binding sites, and other alterations of
      cellular functions. To identify possible mechanisms underlying nicotine-induced
      changes in nAChR numbers and function, we defined changes in gene expression in
      neuron-like, SH-SY5Y human neuroblastoma cells following 24 h of continuous
      exposure to 1 mM nicotine. This treatment condition produces both functional
      inactivation and upregulation of nAChR. Repeat and cross-controlled microarray (
      approximately 5000 genes queried) analyses revealed 163 genes whose expression
      was consistently altered at the p<0.01 level following nicotine treatment.
      Quantitative, real-time, reverse transcription-polymerase chain reaction analyses
      confirmed altered expression of thirteen out of fourteen of these genes chosen
      for further study, including contactin 1, myozenin 2, and ubiquitin-conjugating
      enzymes E2C and E2S. Inhibition or reversal of these effects by the general nAChR
      antagonist, d-tubocurarine, indicated that gene expression changes are dependent
      on nAChR activation. Studies using other nAChR subtype-selective antagonists
      identified gene expression changes that required activation of both alpha7- and
      alpha3*-nAChR, alpha7-nAChR alone, or either alpha7- or alpha3beta4*-nAChR,
      suggesting some convergent and some divergent pathways of gene activation coupled
      to these nAChR subtypes. These results suggest that longer-term physiological and
      psychological effects of nicotine exposure and changes in nAChR expression may be
      due in part to effects on gene expression initiated by interactions with nAChR.

PMID- 16949558
TI  - Sex differences in coxsackievirus B3-induced myocarditis: IL-12Rbeta1 signaling
      and IFN-gamma increase inflammation in males independent from STAT4.
AB  - Cardiovascular disease is the number one killer of men and women in North
      America. Male BALB/c mice infected with coxsackievirus B3 (CVB3) develop more
      severe inflammatory heart disease compared to female mice, similar to the
      increased heart disease that occurs in men. We show here that increased
      inflammation in male mice is not due to increased viral replication in the heart,
      but associated with increased proinflammatory cytokines IL-1beta, IL-18 and IFN
      gamma. We have previously reported that IL-12Rbeta1 signaling increases CVB3
      induced myocarditis and IL-1beta/IL-18 levels in males, while IL-12(p35)/STAT4
      induced IFN-gamma does not alter the severity of acute disease. However, whether
      differences exist between males and females in these two cytokine signaling
      pathways is unknown. In this study, we examined sex differences in 1) IL-12Rbeta1
      signaling or 2) STAT4/IFN-gamma pathways following CVB3 infection in BALB/c mice.
      We found that male and female mice deficient in IL-12Rbeta1 had decreased
      inflammation and viral replication in the heart, indicating that IL-12Rbeta1
      signaling increases myocarditis in both sexes. In contrast, STAT4 deficiency did
      not alter the sex difference in myocarditis, with males maintaining increased
      inflammation over females. IFN-gamma deficient males, however, had decreased
      myocarditis and viral replication compared to females. Thus, IFN-gamma increases
      inflammation in males independent from STAT4. These results demonstrate that sex
      differences greatly influence viral replication and the severity of acute CVB3
      induced myocarditis.

PMID- 16949559
TI  - Intracerebroventricular administration of creatine protects against damage by
      global cerebral ischemia in rat.
AB  - Although a large body of evidence shows that pretreatment of brain tissue with
      creatine protects against anoxic injury in vitro, only a couple of papers have
      investigated creatine protection in vivo, and they yielded conflicting results.
      We attempted to clarify how creatine may be protective in an in vivo model of
      global cerebral ischemia (GCI). We administered creatine either before of after
      GCI. We decided to administer it by intracerebroventricular infusion, to maximize
      its bioavailability to the brain. Our findings show that creatine is clearly
      protective in vivo when administered before ischemia. In that case, histological
      evaluation of damage was consistently improved in all regions examined, and
      neurological score was better in creatine-treated rats than in controls. When
      administered after ischemia, histology was improved in the hippocampus, while
      only a not significant trend toward improvement was observed in the cerebral
      cortex and in the caudo-putamen. Neurological score was not improved by creatine
      administration after GCI. Our findings show that creatine administration is
      protective in vivo. Such protection was clear in the case of pretreatment, and
      was present, to a lesser degree, when treatment was started after ischemia. Our
      results should encourage further research in the possible role of creatine
      therapy in neuroprotection.

PMID- 16949560
TI  - Neurochemical and behavioral effects of bupropion and mecamylamine in the
      presence of nicotine.
AB  - The primary mechanism of action of bupropion, a smoking cessation drug, is
      commonly believed to involve the dopaminergic system although evidence exists
      that bupropion also has effects at nicotinic acetylcholine receptors (nAChRs).
      This study evaluated the disruptive effects of nicotine on response rates in the
      presence of bupropion and the nAChR antagonist, mecamylamine, as well as the
      ability of these drugs to alter nicotine-stimulated nAChR function in various
      brain areas. Rats were trained to respond on a single lever under a variable
      interval 15 (VI15) schedule for food reinforcement. Initially, dose effect curves
      were generated for nicotine, bupropion and mecamylamine. Upon determining the
      dose of nicotine (1.2 mg/kg) effective in completely disrupting rates of
      responding, it was established that both mecamylamine and bupropion block
      nicotine's rate-reducing effects. This result suggests that bupropion shares
      behavioral effects with mecamylamine when administered in the presence of
      nicotine. To explore this relationship further, the effect of in vivo
      administration of bupropion or mecamylamine on nicotine-stimulated (86)Rb(+)
      efflux was studied in synaptosomes prepared from the frontal cortex, hippocampus,
      striatum and thalamus. Nicotine-stimulated (86)Rb(+) efflux from all brain
      regions was significantly reduced in rats administered 3.0 mg/kg mecamylamine
      (s.c.) 15 min prior to dissection compared to control rats. In contrast, a
      significant increase in nicotine-stimulated (86)Rb(+) efflux was observed in all
      brain regions from rats administered 30.0 mg/kg bupropion (s.c.) 15 min prior to
      dissection compared to control rats. Taken together these results demonstrate
      that when administered in the presence of nicotine, bupropion elicits unique
      pharmacological differences such that it exhibits both nAChR agonist- and
      antagonistic-like effects.

PMID- 16949561
TI  - Enhanced biosynthesis of glutathione in the spiral ganglion of the cochlea after
      in vivo treatment with dexamethasone in mice.
AB  - Glucocorticoids have been widely used as a therapeutic drug for sudden
      sensorineural hearing loss. However, very little is known about the mechanism(s)
      underlying the protective effect of glucocorticoids against hearing loss. As an
      approach toward elucidating the mechanism(s), we evaluated the effects of
      dexamethasone (DEX) treatment on the biosynthesis of GSH in the mouse cochlea in
      vivo. The systemic administration of DEX led to a significant increase in the
      total GSH level in the cochlea 2 to 24 h later. This DEX-induced increase in GSH
      occurred selectively in the spiral ganglion, but not significantly in the lateral
      wall tissues or in the organ of Corti. Furthermore, RT-PCR analysis revealed that
      DEX treatment resulted in enhanced expression of gamma-glutamylcysteine
      synthetase (gamma-GCS), which is the rate-limiting enzyme for de novo GSH
      synthesis, 1 to 24 h after the treatment. In addition to enhancing GSH
      biosynthesis, DEX treatment was effective in reducing lipid peroxidation in the
      cochlea. Taken together, DEX has the ability to facilitate GSH biosynthesis
      through enhanced expression of gamma-GCS in the cochlear spiral ganglion.

PMID- 16949562
TI  - A new and efficient entry to D-xylo-hexos-4-ulose and some derivatives thereof
      through epoxidation of the 3,4-hexeno derivative of diacetone-D-glucose.
AB  - A new preparation of D-xylo-hexos-4-ulose (1) and of its 3-m-chlorobenzoate (2)
      has been devised using the epoxidation of 3-deoxy-1,2:5,6-di-O-isopropylidene-D
      erythro-hex-3-enofuranose (6) as the key step. The epoxidation of 6 in CH2Cl2
      furnished with high yield 1,2:5,6-di-O-isopropylidene-3-O-m-chlorobenzoyl-4-C
      hydroxy-D-xylo-hexos-4-ulo-1,4-furanose as a mixture of C-4 hemiacetal anomers
      (7a,b), which, on acid hydrolysis, gave a tautomeric mixture of 3-O-m
      chlorobenzoyl-D-xylo-hexos-4-ulose (2) with an overall 60% yield from 6. The
      formation of 4-C-methoxy-diacetone-D-glucose derivatives (11a,b) through
      epoxidation-methanolysis of 6, took place with reduced yield because of the
      competition between m-chlorobenzoic acid (MCBA) and methanol to the opening by
      attack at C-4 of the intermediate epoxide and the formation of acyclic products
      arising from the alternative nucleophilic attack at C-1. Acid hydrolysis of
      derivatives 11 gave D-xylo-hexos-4-ulose (1) with a 35% overall yield from 6. NMR
      analysis showed that 2 is composed, in CD3CN, mainly by a 7:3 mixture of 4-keto
      alpha- and beta-pyranose forms, while 1, in D2O, is present as a more complex
      mixture constituted mainly by 4-keto-alpha- and beta-pyranoses and their
      respective hydrates in a 17:15:34:34 ratio.

PMID- 16949563
TI  - Cellular electroporation induces dedifferentiation in intact newt limbs.
AB  - Newts have the remarkable ability to regenerate lost appendages including their
      forelimbs, hindlimbs, and tails. Following amputation of an appendage, the wound
      is rapidly closed by the migration of epithelial cells from the proximal
      epidermis. Internal cells just proximal to the amputation plane begin to
      dedifferentiate to form a pool of proliferating progenitor cells known as the
      regeneration blastema. We show that dedifferentiation of internal appendage cells
      can be initiated in the absence of amputation by applying an electric field
      sufficient to induce cellular electroporation, but not necrosis or apoptosis. The
      time course for dedifferentiation following electroporation is similar to that
      observed following amputation with evidence of dedifferentiation beginning at
      about 5 days postelectroporation and continuing for 2 to 3 weeks. Microarray
      analyses, real-time RT-PCR, and in situ hybridization show that changes in early
      gene expression are similar following amputation or electroporation. We conclude
      that the application of an electric field sufficient to induce transient
      electroporation of cell membranes induces a dedifferentiation response that is
      virtually indistinguishable from the response that occurs following amputation of
      newt appendages. This discovery allows dedifferentiation to be studied in the
      absence of wound healing and may aid in identifying genes required for cellular
      plasticity.

PMID- 16949565
TI  - The Grainyhead-like epithelial transactivator Get-1/Grhl3 regulates epidermal
      terminal differentiation and interacts functionally with LMO4.
AB  - Defective permeability barrier is an important feature of many skin diseases and
      causes mortality in premature infants. To investigate the control of barrier
      formation, we characterized the epidermally expressed Grainyhead-like epithelial
      transactivator (Get-1)/Grhl3, a conserved mammalian homologue of Grainyhead,
      which plays important roles in cuticle development in Drosophila. Get-1 interacts
      with the LIM-only protein LMO4, which is co-expressed in the developing mammalian
      epidermis. The epidermis of Get-1(-/-) mice showed a severe barrier function
      defect associated with impaired differentiation of the epidermis, including
      defects of the stratum corneum, extracellular lipid composition and cell adhesion
      in the granular layer. The Get-1 mutation affects multiple genes linked to
      terminal differentiation and barrier function, including most genes of the
      epidermal differentiation complex. Get-1 therefore directly or indirectly
      regulates a broad array of epidermal differentiation genes encoding structural
      proteins, lipid metabolizing enzymes and cell adhesion molecules. Although
      deletion of the LMO4 gene had no overt consequences for epidermal development,
      the epidermal terminal differentiation defect in mice deleted for both Get-1 and
      LMO4 is much more severe than in Get-1(-/-) mice with striking impairment of
      stratum corneum formation. These findings indicate that the Get-1 and LMO4 genes
      interact functionally to regulate epidermal terminal differentiation.

PMID- 16949564
TI  - Meiotic resumption in response to luteinizing hormone is independent of a Gi
      family G protein or calcium in the mouse oocyte.
AB  - The signaling pathway by which luteinizing hormone (LH) acts on the somatic cells
      of vertebrate ovarian follicles to stimulate meiotic resumption in the oocyte
      requires a decrease in cAMP in the oocyte, but how cAMP is decreased is unknown.
      Activation of Gi family G proteins can lower cAMP by inhibiting adenylate cyclase
      or stimulating a cyclic nucleotide phosphodiesterase, but we show here that
      inhibition of this class of G proteins by injection of pertussis toxin into
      follicle-enclosed mouse oocytes does not prevent meiotic resumption in response
      to LH. Likewise, elevation of Ca2+ can lower cAMP through its action on Ca2+
      sensitive adenylate cyclases or phosphodiesterases, but inhibition of a Ca2+ rise
      by injection of EGTA into follicle-enclosed mouse oocytes does not inhibit the LH
      response. Thus, neither of these well-known mechanisms of cAMP regulation can
      account for LH signaling to the oocyte in the mouse ovary.

PMID- 16949566
TI  - Identification of a novel population of adrenal-like cells in the mammalian
      testis.
AB  - Steroidogenic cells of the adrenal and gonad are thought to be derived from a
      common primordium that divides into separate tissues during embryogenesis. In
      this paper, we show that cells with mixed adrenal and Leydig cell properties are
      found dispersed in the insterstitium of the embryonic and adult mouse testis.
      They express the adrenal markers Cyp11b1 and Cyp21 and respond to ACTH.
      Consistent with these properties, we show that the embryonic testis produces the
      adrenal steroid corticosterone. These cells also express Cyp17 and respond to hCG
      stimulation but do not express the Leydig specific marker Insl3 showing that they
      are a population of steroidogenic cells distinct from Leydig cells. Based on
      their properties, we refer to these cells as adrenal-like cells of the testis and
      propose that they are the mouse equivalent of the precursors of human adrenal
      rests, tumors found primarily in male patients with congenital adrenal
      hyperplasia. Organ culture studies show that ACTH-responsive cells are present at
      the gonad/mesonephros border and seem to migrate into the XY but not the XX gonad
      during development. Consistent with this, using transgenic Cyp11a1 reporter mice,
      we definitively show that steroidogenic cells can migrate from the mesonephros
      into the XY gonad. We also show that the region between the mesonephros and the
      gonad harbors steroidogenic cell precursors that are repressed by the presence of
      the mesonephros. We propose that this region is the source of the adrenal-like
      cells that migrate into the testis as it develops and are activated when Leydig
      cells differentiate. These studies reveal the complex nature of steroidogenic
      cell differentiation during urogenital development.

PMID- 16949567
TI  - Lack of plasminogen leads to milk stasis and premature mammary gland involution
      during lactation.
AB  - The extracellular serine protease, plasmin, is activated from its precursor,
      plasminogen (Plg), by the urokinase-type and tissue-type Plg activators (uPA and
      tPA respectively). One of the main plasmin substrates, fibrin, is formed from
      fibrinogen via thrombin activity. We have previously shown that mice deficient
      for Plg are strikingly less able to support a litter during lactation compared to
      wild type mice. Here we suggest a mechanism responsible for this lactation
      defect. Reduced epithelial content and increased apoptosis are observed in Plg
      deficient mammary glands at lactation day 7. Immunofluorescence analysis reveals
      the presence of fibrin(ogen) in the stroma surrounding mammary alveoli and
      adipocytes and identifies fibrin(ogen) as a component of breast milk in both wild
      type and Plg-deficient mice. Furthermore, a large accumulation of fibrin(ogen)
      together with apoptotic epithelial cells is observed in the lactating mammary
      alveoli and ducts of some Plg-deficient mice. This suggests that fibrin plays a
      key role in the malfunction of mammary glands in the absence of Plg, possibly
      through blockade of mammary ducts inducing milk stasis, inhibiting milk expulsion
      and thereby inducing premature apoptosis and involution.

PMID- 16949568
TI  - Spook and Spookier code for stage-specific components of the ecdysone
      biosynthetic pathway in Diptera.
AB  - Ecdysteroids regulate many key developmental events in arthropods including
      molting and metamorphosis. Recently, members of the Drosophila Halloween group of
      genes, that are required for embryonic viability and cuticle deposition, have
      been shown to code for several cytochrome P450 enzymes that catalyze the terminal
      hydroxylation steps in the conversion of cholesterol to the molting hormone 20
      hydroxyecdysone. These P450s are conserved in other insects and each is thought
      to function throughout development as the sole mediator of a particular
      biosynthetic step since, where analyzed, each is expressed at all stages of
      development and shows no closely related homolog in their respective genomes. In
      contrast, we show here that several dipteran genomes encode two novel, highly
      related, microsomal P450 enzymes, Cyp307A1 and Cyp307A2, that likely participate
      as stage-specific components of the ecdysone biosynthetic machinery. This
      hypothesis comes from the observation that Cyp307A1 is encoded by the Halloween
      gene spook (spo), but unlike other Halloween class genes, Dmspo is not expressed
      during the larval stages. In contrast, Cyp307a2, dubbed spookier (spok), is
      expressed primarily during larval stages within the prothoracic gland cells of
      the ring gland. RNAi mediated reduction in the expression of this heterochromatin
      localized gene leads to arrest at the first instar stage which can be rescued by
      feeding the larva 20E, E or ketodiol but not 7dC. In addition, spok expression is
      eliminated in larvae carrying mutations in molting defective (mld), a gene
      encoding a nuclear zinc finger protein that is required for production of
      ecdysone during Drosophila larval development. Intriguingly, mld is not present
      in the Bombyx mori genome, and we have identified only one spook homolog in both
      Bombyx and Manduca that is expressed in both embryos and larva. These studies
      suggest an evolutionary split between Diptera and Lepidoptera in how the ecdysone
      biosynthetic pathway is regulated during development.

PMID- 16949569
TI  - Blimp-1 is an essential component of the genetic program controlling development
      of the pectoral limb bud.
AB  - Formation of paired limbs in vertebrate embryos has long been a particularly
      useful paradigm for the study of pattern formation. Here, we show that Blimp-1, a
      SET domain and zinc finger-containing transcriptional factor, plays an important
      role in the development of the pectoral fins of the zebrafish structures that are
      homologous to forelimbs of amniotes. The blimp-1 gene is expressed dynamically in
      the mesenchyme as well as the ectodermal cells of the early fin bud, and later,
      in the cells of the apical ectodermal ridge (AER) of the outgrowing fin.
      Consistent with this expression profile, loss of Blimp-1 activity severely
      impairs fin outgrowth and patterning. We present evidence that blimp-1 functions
      downstream of tbx5 and fgf24 and therefore is not required for the initial
      specification of the fin bud primordia. Subsequently, however, its function is
      necessary for the induction of fgf10 and sonic hedgehog in the mesenchyme. In
      addition, Blimp-1 activity is absolutely critical for the proper induction of
      gene expression in the ectoderm and establishment of the AER. Taken together,
      these results identify an additional layer of control in the genetic pathway that
      operates in the developing limb and provides novel insights into regulatory
      mechanisms that organize its pattern.

PMID- 16949570
TI  - Geochemistry and origin of PM10 in the Huelva region, Southwestern Spain.
AB  - The results of chemical analysis of PM(10) atmospheric dust samples collected
      between July 2001 and June 2002 in rural and urban background monitoring stations
      in Huelva (South-western Spain) are reported. In order to identify the sources
      and quantify their contribution to PM(10), principal component analysis and
      receptor modelling techniques were performed using independent variables of the
      complete series of concentrations of PM(10) contents. The Ria of Huelva is
      considered to be one of the high industrial estates in Spain, where several
      metallurgical, petrochemical and fertilizer industrial estates are located,
      surrounded by areas of a high ecological interest such as Donana National Park.
      Annual means of 29-33 and 37 micro g PM(10)m(-3) were obtained for the study
      period in rural and urban monitoring stations, respectively. These values are
      below the mean annual limit value for 2005 and onwards from the Directive
      1999/30/EC [EU, 1999. 1999/30/CE Council Directive relating to limit values for
      sulphur dioxide, nitrogen dioxide and oxide of nitrogen, particulate matter and
      lead in ambient air. The Council of the European Union]. High PM(10) episodes in
      rural and urban areas occurred during African dust events. Episodically, the
      emissions of plumes from industrial estates reach rural areas causing peak
      episodes of PO(4)(3-) Cu, Ti Pb and As. Anthropogenic particles arising from
      metallurgical emissions (pyrite, chalcopyrite and sphalerite) were observed in
      the rural sites. The annual mean As concentrations measured in PM(10) in the city
      of Huelva and surrounding rural areas (144 and 84-51mg Askg(-1) in PM(10),
      respectively) are several times high the concentrations obtained in other Spanish
      monitoring stations (7-57mg Askg(-1)). The source apportionment analyses allowed
      the quantification of the contribution to PM(10) of an industrial mixed source in
      the rural background.

PMID- 16949571
TI  - Pharmacological therapies against soman-induced seizures in rats 30 min following
      onset and anticonvulsant impact.
AB  - Systemic administration does not allow a clear differentiation between the
      anticonvulsant properties of GABAA (gamma-aminobutyric acid) modulators. For this
      reason, various GABAA modulators have previously been micro-infused into seizure
      controlling substrates (area tempestas, substantia nigra) in the rat brain as a
      screening method for potential systemic administration. The purpose of the
      present study was to examine the anticonvulsant impact of the GABAergic
      modulators muscimol, ethanol, and propofol (screened by micro-infusions) when
      each drug was combined with procyclidine and administered systemically. The
      results showed that all 3 combinations could effectively terminate soman-induced
      (100 microg/kg s.c.) seizures when administered 30-35 min after onset.
      Procyclidine and propofol were considered as the most relevant double regimen to
      replace a previous triple regimen (procyclidine, diazepam, pentobarbital) against
      soman-induced seizures. Additionally, it was shown that unilateral implantation
      of hippocampal electrodes resulted in increased resistance to aphagia/adipsia and
      neuropathology, but not to lethality following soman. Efficient pharmacological
      treatment of soman-induced seizures at an early stage (< 20 min) is crucial to
      avoid neuropathology and cognitive deficits.

PMID- 16949572
TI  - Beneficial effect of tachykinin NK1 receptor antagonism in the development of
      hapten-induced colitis in mice.
AB  - The gastro-intestinal tract is highly innervated by both intrinsic and extrinsic
      sensory nerves and this neuronal component is thought to play a role in local
      inflammatory responses. This in vivo study was designed to determine the function
      of substance P and the tachykinin NK1 receptor in the pathogenesis of
      inflammatory bowel disease by the use of the specific antagonist RP 67580. The
      dinitrofluorobenzene (DNFB)-induced colonic hypersensitivity model is associated
      with increased levels of substance P in the colon. The tachykinin NK1 receptor
      antagonist RP 67580 was used to investigate the role of substance P on the
      development of diarrhea, mast cell infiltration and activation, colonic tissue
      damage, hypertrophy of colonic lymphoid structures and leukocyte infiltration.
      The formation of watery diarrhea could completely be abrogated by treatment with
      RP 67580 in DNFB-sensitized animals 72 h after challenge. Antagonizing the
      tachykinin NK1 receptor in these animals also resulted in significantly reduced
      colonic patch hypertrophy, leukocyte recruitment and tissue damage. Total levels
      of substance P in the colon of DNFB-sensitized mice treated with the inactive
      enantiomer of the tachykinin NK1 receptor antagonist were significantly higher
      compared to DNFB-sensitized mice treated with RP 67580 72 h after challenge.
      Although RP 67580 was capable of reducing the total number of mast cells present
      in the colon, mast cell activation was not affected by this treatment. In
      conclusion, in this chemically-induced immunological model for inflammatory bowel
      disease we demonstrated an important role for tachykinin NK1 receptors, and its
      ligand substance P, in the development of colitis downstream from mast cell
      activation.

PMID- 16949573
TI  - Transcriptional networks in a rat model for nonalcoholic fatty liver disease: a
      microarray analysis.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a common hepatic
      condition that may progress to end-stage liver disease. High-fat diets in animals
      reproduce many of the features found in nonalcoholic steatohepatitis. OBJECTIVE:
      To understand how various dietary or genetic factors influence the development of
      fatty liver and consequently NAFLD, we performed microarray-based expression
      profiling of genes, induced by fish oil and dextrose diet, a putative mediator of
      alcohol-like effects on the liver of the female rat. DESIGN: Male and age-matched
      female rats were fed fish oil and dextrose for 4 weeks. Hepatic RNA from each
      sample was extracted and used for microarray analysis. RESULTS: A large number of
      genes underwent significant changes in the female liver as compared to male
      controls. In the female rat liver, biological theme analysis demonstrated a shift
      in the transcriptional program which included upregulation of genes involved in
      lipid metabolism, chaperone activity, mitochondrial and oxidoreductase activity
      combined with downregulation of genes involved in nucleic acid metabolism. The
      differential expression of genes of interest identified by microarray technique
      was validated by real-time reverse transcription-polymerase chain reaction.
      Ingenuity computational pathway analysis tools were used to identify specific
      regulatory networks of genes operative in promoting liver injury. CONCLUSIONS:
      The use of networks stated above allowed us to identify genes involved in cell
      death, apoptosis, peroxisome proliferator-activated receptor alpha-regulated
      lipid metabolism and mitogen-activated protein kinase signaling pathways.

PMID- 16949574
TI  - Okadaic acid overcomes the blocked cell cycle caused by depleting Cdc2-related
      kinases in Trypanosoma brucei.
AB  - Mitosis and cytokinesis are highly coordinated in eukaryotic cells. But procyclic
      form Trypanosoma brucei under G1 or mitotic arrest is still capable of dividing,
      resulting in anucleate daughter cells (zoids). Okadaic acid (OKA), an inhibitor
      of protein phosphatases PP1 and PP2A, is known to inhibit kinetoplast replication
      and cell division yielding multinucleate cells with single kinetoplasts. However,
      when OKA was applied to cells arrested in G1 or G2/M phase via RNAi knockdown of
      specific cdc2-related kinases (CRKs), DNA synthesis and nuclear division were
      resumed without kinetoplast replication or cell division, resulting in
      multinucleate cells as in the wild type. Cells arrested in G2/M via depleting the
      mitotic cyclin CycB2 or an aurora B kinase homologue TbAUK1 were, however, not
      released by OKA treatment. The phenomenon is thus similar to the OKA activation
      of Cdc2 in Xenopus oocyte by inhibiting PP2A [Maton, et al., Differential
      regulation of Cdc2 and Aurora-A in Xenopus oocytes: a crucial role of phosphatase
      2A. J. Cell Sci. 118 (2005) 2485-2494]. A simultaneous knockdown of the seven
      PP1s or the PP2A catalytic subunit in T. brucei by RNA interference did not,
      however, result in multinucleate cells. This could be explained by assuming a
      negative regulation, either directly or indirectly, of CRK by an OKA-sensitive
      phosphatase, which could be a PP2A as in the Xenopus oocyte and a positive
      regulation of kinetoplast replication by an OKA-susceptible protein(s). Test of a
      PP2A-specific inhibitor, fostriecin, on cells arrested in G2/M via CRK depletion
      or a knockdown of the PP2A catalytic subunit from the CRK-depleted cells both
      showed a partial lift of the G2/M block without forming multinucleate cells.
      These observations support the abovementioned assumption and suggest the presence
      of a novel OKA-sensitive protein(s) regulating kinetoplast replication that still
      remains to be identified.

PMID- 16949575
TI  - The Rothmund-Thomson gene product RECQL4 localizes to the nucleolus in response
      to oxidative stress.
AB  - Mutations in the RECQL4 helicase gene have been linked to Rothmund-Thomson
      syndrome (RTS), which is characterized by poikiloderma, growth deficiency, and a
      predisposition to cancer. Examination of RECQL4 subcellular localization in live
      cells demonstrated a nucleoplasmic pattern and, to a lesser degree, staining in
      nucleoli. Analysis of RECQL4-GFP deletion mutants revealed two nuclear
      localization regions in the N-terminal region of RECQL4 and a nucleolar
      localization signal at amino acids 376-386. RECQL4 localization did not change
      after treatment with the DNA-damaging agents bleomycin, etoposide, UV irradiation
      and gamma irradiation, in contrast to the Bloom and Werner syndrome helicases
      that relocate to distinct nuclear foci after damage. However, in a significant
      number of cells exposed to hydrogen peroxide or streptonigrin, RECQL4 accumulated
      in nucleoli. Using a T7 phage display screen, we determined that RECQL4 interacts
      with poly(ADP-ribose) polymerase-1 (PARP-1), a nuclear enzyme that promotes
      genomic integrity through its involvement in DNA repair and signaling pathways.
      The RECQL4 nucleolar localization was inhibited by pretreatment with a PARP-1
      inhibitor. The C-terminal portion of RECQL4 was found to be an in vitro substrate
      for PARP-1. These results demonstrate changes in the intracellular localization
      of RECQL4 in response to oxidative stress and identify an interaction between
      RECQL4 and PARP-1.

PMID- 16949576
TI  - Systemically transferred hematopoietic stem cells home to the subretinal space
      and express RPE-65 in a mouse model of retinal pigment epithelium damage.
AB  - Stem cell regeneration of damaged tissue has recently been reported in many
      different organs. Since the loss of retinal pigment epithelium (RPE) in the eye
      is associated with a major cause of visual loss - specifically, age-related
      macular degeneration - we investigated whether hematopoietic stem cells (HSC)
      given systemically can home to the damaged subretinal space and express markers
      of RPE lineage. Green fluorescent protein (GFP) cells of bone marrow origin were
      used in a sodium iodate (NaIO(3)) model of RPE damage in the mouse. The optimal
      time for adoptive transfer of bone marrow-derived stem cells relative to the time
      of injury and the optimal cell type [whole bone marrow, mobilized peripheral
      blood, HSC, facilitating cells (FC)] were determined by counting the number of
      GFP(+) cells in whole eye flat mounts. Immunocytochemistry was performed to
      identify the bone marrow origin of the cells in the RPE using antibodies for
      CD45, Sca-1, and c-kit, as well as the expression of the RPE-specific marker, RPE
      65. The time at which bone marrow-derived cells were adoptively transferred
      relative to the time of NaIO(3) injection did not significantly influence the
      number of cells that homed to the subretinal space. At both one and two weeks
      after intravenous (i.v.) injection, GFP(+) cells of bone marrow origin were
      observed in the damaged subretinal space, at sites of RPE loss, but not in the
      normal subretinal space. The combined transplantation of HSC+FC cells appeared to
      favor the survival of the homed stem cells at two weeks, and RPE-65 was expressed
      by adoptively transferred HSC by four weeks. We have shown that systemically
      injected HSC homed to the subretinal space in the presence of RPE damage and that
      FC promoted survival of these cells. Furthermore, the RPE-specific marker RPE-65
      was expressed on adoptively transferred HSC in the denuded areas.

PMID- 16949577
TI  - Serum cytokines of the 20 Krad-irradiated S. mansoni cercariae vaccinated,
      primary and superinfected Cercopethicus aethiops aethiops.
AB  - Appropriate animal models are necessary to better understand the immune response
      in schistosomiasis. Schistosoma mansoni infection was established using
      irradiated cercariae in Cercopithecus aethiops aethiops (Grivet monkey) to
      describe immune responses of the serum cytokines, IL-4, IL-10, IL-12, IFN- gamma,
      and TNF-alpha. Intraperitoneal irradiated cercariae immunization on three
      occasions resulted in some differences of cytokine production. In primary
      infection, IL-4 was significantly raised (p=0.03) in the immunized monkeys, and
      there was an insignificant increase (p>0.05) in IL-10. However, ova excretion did
      not influence the cytokines, except in the controls where both IL-4 and IL-10
      were significantly increased (p<0.05). In the controls, IL-12 and INF-gamma
      levels were lower after ova excretion, but the inflammatory TNF-alpha increased
      (p=0.049) and these findings can be associated with more liver pathogenesis in
      the group. Thus, this work has indicated the potential importance of anti
      schistosome vaccine studies on the grivet monkeys.

PMID- 16949578
TI  - Light-responsive transcriptional regulation of the suf promoters involved in
      cyanobacterium Synechocystis sp. PCC 6803 Fe-S cluster biogenesis.
AB  - The widely conserved SUF system is involved in Fe-S cluster repair and
      biogenesis. In cyanobacterium Synechocystis sp. PCC 6803, transcription of the
      sufBCDS operon encoding the Suf complex is negatively regulated by the upstream
      sufR gene encoded by the complementary strand. In this report, two promoters for
      the sufBCDS operon (P1 and P2) and another promoter for sufR (PsufR) was
      identified, and it was shown that P1 was activated by a shift to high light
      conditions. We also showed that Thermosynechococcus SufR negatively regulated P1
      and PsufR but not P2, in a reconstituted in vitro transcription system using
      His(6)-tagged RNA polymerase.

PMID- 16949579
TI  - Mapping of barley alpha-amylases and outer subsite mutants reveals dynamic high
      affinity subsites and barriers in the long substrate binding cleft.
AB  - Subsite affinity maps of long substrate binding clefts in barley alpha-amylases,
      obtained using a series of maltooligosaccharides of degree of polymerization of 3
      12, revealed unfavorable binding energies at the internal subsites -3 and -5 and
      at subsites -8 and +3/+4 defining these subsites as binding barriers. Barley
      alpha-amylase 1 mutants Y105A and T212Y at subsite -6 and +4 resulted in release
      or anchoring of bound substrate, thus modifying the affinities of other high
      affinity subsites (-2 and +2) and barriers. The double mutant Y105A-T212Y
      displayed a hybrid subsite affinity profile, converting barriers to binding
      areas. These findings highlight the dynamic binding energy distribution and the
      versatility of long maltooligosaccharide derivatives in mapping extended binding
      clefts in alpha-amylases.

PMID- 16949580
TI  - Mutational analysis of 6-aminohexanoate-dimer hydrolase: relationship between
      nylon oligomer hydrolytic and esterolytic activities.
AB  - Carboxylesterase (EII') from Arthrobacter sp. KI72 has 88% homology to 6
      aminohexanoate-dimer hydrolase (EII) and possesses ca. 0.5% of the level of 6
      aminohexanoate-linear dimer (Ald)-hydrolytic activity of EII. To study
      relationship between Ald-hydrolytic and esterolytic activities, random mutations
      were introduced into the gene for Hyb-24 (an EII/EII' hybrid with the majority of
      the sequence deriving for EII' and possessing an EII'-like level of Ald
      hydrolytic activity). Either a G181D or a D370Y substitution in Hyb-24 increased
      the Ald-hydrolytic activity ca. 10-fold, and a G181D/D370Y double substitution
      increased activity ca. 100-fold. On the basis of kinetic studies and the three
      dimensional structure of the enzyme, we suggest that binding of Ald is improved
      by these mutations. D370Y increased esterolytic activity for glycerylbutyrate ca.
      30-50-fold, whereas G181D decreased the activity to 30% of the parental enzyme.

PMID- 16949581
TI  - Zinc ions stimulate the cooperative RNA binding of hordeiviral gammab protein.
AB  - A small regulatory gammab protein of the Poa semilatent hordeivirus (PSLV)
      contains two zinc finger-like motifs separated by a basic motif in the N-terminal
      part and a C-terminal coiled-coil motif. Interactions of the recombinant PSLV
      gammab protein and its mutants with various RNAs (ssRNA, dsRNA, ssRNA
      oligonucleotides) and ssDNA were studied in gel-shift assays. The results
      demonstrated that zinc ions are essential for effective nucleic-acid-binding
      activity of the gammab protein, suggesting the important role of zinc finger
      motifs in these interactions. Deletion of the C-proximal coiled-coil region did
      not affect highly cooperative RNA-protein binding, indicating that the N-terminal
      part of the protein contributes to the protein-protein interactions needed for
      the protein-RNA cooperativity.

PMID- 16949582
TI  - Functions of the MAPK family in vertebrate-development.
AB  - The mitogen activated protein kinase (MAPK) family, consisting of the
      extracellular signal regulated protein kinase, c-Jun amino terminal MAPK and p38
      subfamilies, is conserved in evolution throughout the plant and animal kingdoms.
      These proteins have been implicated in diverse cellular processes including cell
      growth, migration, proliferation, differentiation, survival and development. Gene
      targeting approaches in mice, chickens, frogs and zebrafish revealed crucial
      roles of MAPK in vertebrate development. Gene-disruption or -silencing often lead
      to lethal effects, therefore the zebrafish ex utero development provides an
      excellent in vivo model to study the function of MAPK in early embryogenesis. In
      this review, we summarize the current understanding of the MAPK family function
      in vertebrate-development and place this into the perspective of possibilities
      for future research.

PMID- 16949583
TI  - FRET analysis reveals a critical conformational change within the Na,K-ATPase
      alpha1 subunit N-terminus during GPCR-dependent endocytosis.
AB  - Dopamine is a major regulator of sodium reabsorption in proximal tubule
      epithelia. It induces the endocytosis of plasma membrane Na,K-ATPase molecules,
      and this results in a reduced capacity of the cells to transport sodium. Dopamine
      induces the phosphorylation of Ser-18 in the alpha1-subunit of Na,K-ATPase.
      Fluorescence resonance energy transfer analysis of cells expressing YFP-alpha1
      and beta1-CFP reveals that treatment of the cells with dopamine increases energy
      transfer between CFP and YFP. This is consistent with a protein conformational
      change that results in the N-terminal end of alpha1 moving closer to the internal
      face of the plasma membrane.

PMID- 16949584
TI  - How T lymphocytes recognize lipid antigens.
AB  - Recognition of lipid antigens by T lymphocytes is well established. Lipids are
      recognized by T cells when presented in association with CD1 antigen-presenting
      molecules. Both microbial and self lipids stimulate specific T lymphocytes, thus
      participating in immune reactions during infections and autoimmune diseases. The
      immune system uses a variety of strategies to solubilise lipid antigens, to
      facilitate their internalization, processing, and loading on CD1 molecules.
      Recent studies in the field of lipid antigen presentation have revealed new
      mechanisms which allow the immune system to sense lipids as stimulatory antigens.

PMID- 16949585
TI  - Correlation of folding kinetics with the number and isomerization states of
      prolines in three homologous proteins of the RNase family.
AB  - Several studies attribute the slower phases in protein folding to prolyl
      isomerizations, and several others do not. A correlation exists between the
      number of prolines in a protein and the complexity of the mechanism with which it
      folds. In this study, we have demonstrated a direct correlation between the
      number of cis-prolyl bonds in a native protein and the complexity with which it
      folds via slower phases by studying the folding of three structurally homologous
      proteins of the ribonuclease family, namely RNase A, onconase and angiogenin,
      which differ in the number and isomerization states of their proline residues.

PMID- 16949586
TI  - Different relevance of inactivation and F468 residue in the mechanisms of hEag1
      channel blockage by astemizole, imipramine and dofetilide.
AB  - The relevance of a point mutation at the C-terminal end of the S6 helix (F468)
      and the introduction of C-type inactivation in the blockage of hEag1 channels by
      astemizole, imipramine and dofetilide was tested. C-type inactivation decreased
      block by astemizole and dofetilide but not imipramine, suggesting different
      binding sites in the channel. F468C mutation increased IC(50) for astemizole and
      imipramine but in contrast to HERG channels, only slightly for dofetilide.
      Together with measurements on recovery of blocking, our observations indicate
      that the mechanism of hEag1 blockage by each of these drugs is different, and
      suggest relevant structural differences between hEag1 and HERG channels.

PMID- 16949587
TI  - Efficacy of luteinizing hormone activity in patients undergoing in vitro
      fertilization and treated only with low-dose recombinant choriogonadotropin alfa
      (Ovidrel) in the late follicular phase.
AB  - Ten good prognosis patients underwent IVF with a new ovarian stimulation protocol
      using only 8 microg of recombinant choriogonadotropin and a GnRH antagonist
      starting at a 14-mm lead follicle. Six of the 10 subjects delivered and all had
      supernumerary embryos for cryopreservation.

PMID- 16949588
TI  - Ectopic pregnancy in a preexisting hydrosalpinx during a spontaneous pregnancy.
AB  - OBJECTIVE: To discuss the possible role of abnormal embryo migration as a cause
      of ectopic pregnancy during IVF with hydrosalpinges. DESIGN: Case report.
      SETTING: University-based reproductive endocrinology and fertility clinic.
      PATIENT(S): A patient presenting with a tubal ectopic pregnancy after spontaneous
      conception in a preexisting hydrosalpinx. INTERVENTION(S): Laparoscopic
      salpingectomy. MAIN OUTCOME MEASURE(S): Ultrasound and operative findings.
      RESULT(S): Case demonstration of abnormal embryo migration into a surgically
      documented preexisting hydrosalpinx during a spontaneous conception.
      CONCLUSION(S): The mechanism of increased tubal ectopic pregnancy rates during
      IVF with hydrosalpinges remains unexplained. This case supports abnormal embryo
      migration due to the hydrosalpinx as a contributing factor.

PMID- 16949589
TI  - Autologous heterotopic transplantation of intact rabbit ovary after frozen
      banking at -196 degrees C.
AB  - OBJECTIVE: To determine the efficiency of intact ovary after cryopreservation and
      transplantation in a rabbit model for limited longevity by revascularization
      ischemia after implantation of frozen-thawed ovarian tissue. Transplantation of
      an intact frozen ovary with microvascular anastomos has been shown to be feasible
      with modern cryobiology and microsurgery. DESIGN: Animal study. SETTING:
      University-based teaching hospital. ANIMAL(S): Twelve 5-month-old mature female
      New Zealand White rabbits. INTERVENTION(S): After bilateral oophorectomy with one
      ovary saved as a control in formalin-fixed and hematoxylin and eosin-stained
      paraffin sections, the contralateral intact ovary was used for autologous
      heterotopic transplantation after freezing and thawing. MAIN OUTCOME MEASURE(S):
      Density of primordial follicles 6 months after transplantation was measured.
      Hormone levels and vaginal cytology were followed throughout the oophorectomy and
      transplantation period. RESULT(S): Ten of 12 rabbits had restored ovarian
      function 1 week after transplantation of their intact cryopreserved ovary. At the
      6-month posttransplantation follow-up, mean primordial follicle density was
      statistically significantly lower in the experimental than in the control ovaries
      (13.99 +/- 3.21 vs. 18.68 +/- 3.86 per high-power field). The remaining two
      rabbits, which had cracked mesentery fat adjacent to the ovary after thawing,
      never regained ovarian function. CONCLUSION(S): With microsurgery,
      cryopreservation of an intact rabbit ovary followed by autologous transplantation
      may overcome revascularization-associated ischemia to save primordial follicles
      and attain reasonable graft longevity.

PMID- 16949590
TI  - A randomized comparison of vaginal misoprostol and dinoprostone for cervical
      priming in nulliparous women before operative hysteroscopy.
AB  - OBJECTIVE: To compare the efficacy and side effects of vaginal misoprostol with
      dinoprostone for cervical priming before operative hysteroscopy and to assess the
      cervicouterine complications related to cervical dilatation and hysteroscopic
      surgery. DESIGN: A prospective randomized study. SETTING: Tertiary university
      hospital. PATIENT(S): Three hundred ten nulliparous women with definite
      intrauterine lesions. INTERVENTION(S): Hysteroscopic surgery of intrauterine
      lesions. MAIN OUTCOME MEASURE(S): Cervical response, outcome, complications of
      hysteroscopic surgery, and side effects of both drugs. RESULT(S): Among the 310
      patients recruited, 152 were randomized to the vaginal misoprostol group and 158
      to the dinoprostone group. Mean cervical dilatation, cervical dilatation rate,
      and mean time for cervical dilatation to Hegar 9 were significantly different
      between the misoprostol group (7.4 +/- 0.8 mm, 70.4%, and 39.5 +/- 18.8 seconds,
      respectively) and the dinoprostone group (7.0 +/- 0.9 mm, 80.4%, and 43.6 +/-
      17.1 seconds, respectively). Cervical tearing during hysteroscopic surgery
      occurred in 3 patients (2.0%) in the misoprostol group and in 12 patients (7.6%)
      in the dinoprostone group. There were more side effects in the misoprostol group.
      The significant difference of side effects between the two groups were abdominal
      pain, vaginal bleeding, and feeling feverish, which occurred in 36.2%, 29.6%, and
      7.2% in the misoprostol group compared to 21.5%, 16.5%, and 1.3%, respectively,
      in the dinoprostone group. CONCLUSION(S): Vaginal misoprostol is more effective
      than dinoprostone for cervical priming in nulliparous women before hysteroscopic
      surgery. Although more side effects occurred in the misoprostol-treated patients,
      they were mild. We suggest using vagina misoprostol for cervical priming instead
      of dinoprostone.

PMID- 16949591
TI  - Expression of leukemia inhibitory factor and its receptors is increased during
      differentiation of human embryonic stem cells.
AB  - OBJECTIVE: To investigate gene expression profiles during the early spontaneous
      differentiation of human embryonic stem cells (hESCs), with particular emphasis
      on leukemia inhibitory factor (LIF)-induced pathways and the ultrastructural
      surface morphology of the undifferentiated and spontaneously differentiated
      hESCs. DESIGN: Prospective experimental study. SETTING: University laboratory.
      PATIENT(S): Four hESC cell lines. INTERVENTION(S): The effect of LIF on receptor
      expression level was studied in cultures. MAIN OUTCOME MEASURE(S): Gene
      expression in the hESC line HS237 was analyzed using microarrays. Real-time
      reverse-transcription polymerase chain reaction was used to validate the
      microarray results in four hESC lines (HS181, HS235, HS237, HS293).
      Immunohistochemistry was used to assay LIF, LIF receptor, and gp130 protein
      expression. Cell surface morphology was studied using scanning electron
      microscopy. RESULT(S): The expression of LIF, LIF receptor, and gp130 messenger
      RNA and protein was increased in spontaneously differentiated HS237 cells
      compared with undifferentiated cells, with high expression of an inhibitor of LIF
      mediated signaling, suppressor of cytokine signaling-1, in undifferentiated
      hESCs. Genes, those expressed specifically and those shared in undifferentiated
      hESCs, differentiated cells, and in fibroblasts, were identified. Supplementation
      with LIF did not affect the LIF receptor expression. CONCLUSION(S): The
      expression of LIF and its receptors is low in undifferentiated hESCs but
      increases during differentiation. Added LIF does not prevent spontaneous
      differentiation. Suppressor of cytokine signaling-1 may prevent LIF signaling in
      hESCs.

PMID- 16949592
TI  - In vivo spermatotoxic effect of chromium as reflected in the epididymal
      epithelial principal cells, basal cells, and intraepithelial macrophages of a
      nonhuman primate (Macaca radiata Geoffroy).
AB  - OBJECTIVE: To understand, through a simulation experiment in a nonhuman primate
      model, the potential in vivo spermatotoxic toxic effect of hexavalent chromium
      (CrVI) in men who are occupationally or environmentally exposed to it. DESIGN:
      Controlled laboratory study. SETTING: Research laboratory in a department of
      endocrinology in a university in India. ANIMAL(S): Male bonnet monkey, Macaca
      radiata Geoffroy. INTERVENTION(S): Monkeys were exposed ad libitum to 100, 200,
      and 400 ppm CrVI, dissolved in drinking water, for a chronic period of 180 days.
      MAIN OUTCOME MEASURE(S): Examination of epididymis with a transmission electron
      microscope and assessment of the effect of CrVI in terms of accumulation of sperm
      derived lipofuscin (LF) material in the principal cells, basal cells, and
      intraepithelial macrophages of the epithelium. RESULT(S): The abundance of basal
      cells and intraepithelial macrophages and the content of LF material in these
      cell types increased. The principal cells phagocytosed from the lumen the dead
      sperm resulting from CrVI exposure and processed them partially into LF material,
      which was acquired by the basal cells and intraepithelial macrophages and
      processed further. The LF material-laden basal cells and intraepithelial
      macrophages appeared to leave the epithelium, accompanied by recruitment of fresh
      basal cells and intraepithelial macrophages. CONCLUSION(S): Occupational or
      environmental exposure to CrVI, as would occur in the tannery, soap, and other
      industries in developing and underdeveloped countries, can be toxic in vivo to
      spermatozoa.

PMID- 16949593
TI  - Reassessment of the methyl derivatization reaction of carbamates with sodium
      hydride/dimethyl sulfoxide/methyl iodide for their determination by gas
      chromatography.
AB  - A deep revision of the carbamate methyl derivatization reaction with sodium
      hydride/dimethyl sulfoxide/methyl iodide was carried out. Representative
      carbamates, R(1)-NH-COO-R(2), mainly N-methyl and N-aryl ones, have been studied
      in order to clarify which carbamates undergo this reaction. Two possible reaction
      routes are proposed; the route depends on the carbamate substituent (-OR(2)
      group) more than on the methyl or aryl groups joined to the NH moiety as
      literature indicates. The classification of carbamates in N-methyl and N-aryl is
      not suitable to predict the methylation pathway. A laboratory-made closed reactor
      allows handling the reagents involved, minimizing hazards and simplifying the
      procedure for rapid analysis.

PMID- 16949594
TI  - Partial filling micellar electrokinetic chromatography analysis of androgens and
      testosterone derivatives using two sequential pseudostationary phases.
AB  - Separation of anabolic and androgenic steroids by micellar electrokinetic
      chromatography (MEKC) has been little studied. Simultaneous separation of the
      endogenous alpha-epimers testosterone and epitestosterone has not been achieved
      with any electroseparation technique. Here, a partial filling micellar
      electrokinetic chromatographic (PF-MEKC) method is described for the analysis of
      three endogenous steroid hormones (androstenedione, testosterone,
      epitestosterone) and two synthetic anabolic steroids (fluoxymesterone,
      methyltestosterone). The resolution efficiency of single-isomer sulphated gamma
      cyclodextrins and the surfactants sodium dodecyl sulphate and sodium taurocholate
      was exploited. The method is based on the sequential introduction of short plugs
      of two different pseudostationary phases into the capillary. The separation was
      completed in less than 10 min. The method can be used in quantitative analysis.
      Linear correlation was obtained between concentration and peak area of 0.996 or
      better. The repeatability (RSD) of the compound peak areas ranged from 3.6%
      (methyltestosterone) to 6.2% (androstenedione). Limits of detection were between
      73 microg/L (testosterone) and 160 microg/L (fluoxymesterone). As a demonstration
      of the method, androstenedione, testosterone and epitestosterone were determined
      in a spiked urine sample.

PMID- 16949595
TI  - Statistical properties of the band-broadening function.
AB  - Statistical properties of the band-broadening function calculated from the
      equilibrium and kinetic theories of Giddings and Eyring are compared with real
      liquid-chromatography elution curves of low-molecular-weight substances and with
      light-scattering elution curves of a high-molecular-weight polystyrene standard
      injected at several concentrations. The curves obtained by liquid chromatography
      agree in a large span of elution times with the theoretical ones and can be
      described by one value of the plate-height. The size exclusion chromatography
      (SEC) elution curves seem to approach the predicted statistical properties with
      decreasing concentration of injected polymer but, in general, a reliable
      prediction of band-broadening (BB) functions in SEC of polymers, especially of
      non-symmetric BB functions near the exclusion limit, seems not possible at this
      point. The relation of the theory with the characteristic-function approach
      developed by Dondi is also discussed.

PMID- 16949597
TI  - Low voltage electrowetting using thin fluoroploymer films.
AB  - This paper investigates the nonideal electrowetting behavior of thin
      fluoroploymer films. Results are presented for a three phase system consisting
      of: (1) an aqueous water droplet containing sodium dodecyl sulfate (SDS), (2)
      phosphorous-doped silicon topped with SiO2 and an amorphous fluoroploymer (aFP)
      insulating top layer on which the droplet is situated, and (3) a dodecane oil
      that surrounds the droplet. The presented measurements indicate that the
      electrowetting equation is valid down to a 6 nm thick aFP film on a 11 nm thick
      SiO2. At this dielectric thickness, a remarkable contact angle change of over 100
      degrees can be achieved with an applied voltage less than 3 V across the system.
      The data also shows that for this water/surfactant/oil system, contact angle
      saturation is independent of the electric field, and is reached when the surface
      energy of the solid-water interface approaches zero.

PMID- 16949596
TI  - Detection, characterization and identification of crucifer phytoalexins using
      high-performance liquid chromatography with diode array detection and
      electrospray ionization mass spectrometry.
AB  - We have analyzed 23 crucifer phytoalexins (e.g. brassinin, dioxibrassinin,
      cyclobrassinin, brassicanals A and C) by HPLC with diode array detection and
      electrospray ionization mass spectrometry (HPLC-DAD-ESI-MS) using both negative
      and positive ion modes. Positive ion mode ESI-MS appeared more sensitive than
      negative ion mode ESI-MS in detecting this group of compounds. A new HPLC
      separation method, new LC-MS and LC-MS(2) data and proposed fragmentation
      pathways, LC retention times, and UV spectra for selected compounds are reported.

PMID- 16949598
TI  - Tunable sustained release properties of "onion-like" phospholipids multilamellar
      vesicles.
AB  - "Onion-type" multilamellar micro-vesicles of phospholipids (spherulites) were
      doped with different amounts of a cationic cosurfactant ((-)N-dodecyl-N
      methylephedrinium bromide) for the purpose of controlling the sustained release
      of anionic drugs. Three weak acid probes (methyl red, chlorophenol red, and
      ibuprofen) were encapsulated in the vesicles as drug models. The kinetics and
      rate of release were studied by absorption spectroscopy and HPLC. The effect of
      probe charge (pH above and below pKa of the probes), of cosurfactant
      concentration and of added salt was investigated. It was found that, above pKa
      (i.e., when the probes are anionic), the release can be almost totally inhibited
      by doping the vesicles with 2.4 wt% of cationic cosurfactant. The release
      properties can even be finely tuned by controlling the amounts of the
      cosurfactant. Salt and pH effects demonstrate the role of electrostatic
      interactions in sustaining the release.

PMID- 16949599
TI  - Adsorption mechanisms of selenium oxyanions at the aluminum oxide/water
      interface.
AB  - Sorption processes at the mineral/water interface typically control the mobility
      and bioaccessibility of many inorganic contaminants such as oxyanions. Selenium
      is an important micronutrient for human and animal health, but at elevated
      concentrations selenium toxicity is a concern. The objective of this study was to
      determine the bonding mechanisms of selenate (SeO4(2-) and selenite (SeO3(2-) on
      hydrous aluminum oxide (HAO) over a wide range of reaction pH using extended X
      ray absorption fine structure (EXAFS) spectroscopy. Additionally, selenate
      adsorption on corundum (alpha-Al2O3) was studied to determine if adsorption
      mechanisms change as the aluminum oxide surface structure changes. The overall
      findings were that selenite forms a mixture of outer-sphere and inner-sphere
      bidentate-binuclear (corner-sharing) surface complexes on HAO, selenate forms
      primarily outer-sphere surface complexes on HAO, and on corundum selenate forms
      outer-sphere surface complexes at pH 3.5 but inner-sphere monodentate surface
      complexes at pH 4.5 and above. It is possible that the lack of inner-sphere
      complex formation at pH 3.5 is caused by changes in the corundum surface at low
      pH or secondary precipitate formation. The results are consistent with a
      structure-based reactivity for metal oxides, wherein hydrous metal oxides form
      outer-sphere complexes with sulfate and selenate, but inner-sphere monodentate
      surface complexes are formed between sulfate and selenate and alpha-Me2O3.

PMID- 16949600
TI  - A study of the collisional fragmentation problem using the Gamma distribution
      approximation.
AB  - The nonlinear fragmentation population balance formulation has been elevated in
      recent years from a prototype for studying nonlinear integro-differential
      equations to a vehicle for analyzing and understanding several physicochemical
      processes of technological interest. The so-called pure collisional
      fragmentation, which is the particular mode of nonlinear fragmentation induced by
      collisions between particles, is studied here. It is shown that the corresponding
      population balance equation admits large time asymptotic (self-similarity)
      solutions for homogeneous fragmentation and collision functions (kernels). The
      self-similar solutions are given in closed form for some simple kernels. Based on
      the shape of the self-similar solutions the method of moments with Gamma
      distribution approximation is employed for transient solution (from initial state
      to establishment of the asymptotic shape) of the collisional fragmentation
      equation. These solutions are presented for several sets of parameters and their
      behavior is discussed rather extensively. The present study is similar to the one
      has already been performed for the case of the much simpler linear fragmentation
      equation [G. Madras, B.J. McCoy, AIChE J. 44 (1998) 647].

PMID- 16949601
TI  - Stage-dependent effects of starvation on the growth, metamorphosis, and
      ecdysteroidogenesis by the prothoracic glands during the last larval instar of
      the silkworm, Bombyx mori.
AB  - The stage-dependent effects of starvation on the growth, metamorphosis, and
      ecdysteroidogenesis of the prothoracic glands during the last larval instar of
      the silkworm, Bombyx mori, were studied in the present study. When last instar
      larvae were starved beginning on day 1 of that instar, all larvae died between
      days 5 and 7 of the instar. Although the prothoracicotropic hormone (PTTH)
      release from the brain-corpus cardiacum-corpus allatum (BR-CC-CA) did not
      significantly change during starvation, a deficiency in PTTH signal transduction
      was maintained, which led to very low levels of hemolymph ecdysteroids after the
      beginning of starvation. However, when starvation began on day 3 of the last
      larval instar, the major hemolymph ecdysteroid peak, preceding larval-pupal
      transformation, occurred 1 day earlier than that in control larvae. Protein
      content of the prothoracic glands in day 3-starved larvae was maintained at a low
      level as compared to that of control larvae. The secretory activity of the
      prothoracic glands in day 3-starved larvae was maintained at a level similar to
      that of control larvae. However, the rate of ecdysteroidogenesis, expressed per
      microgram of glandular protein, was greatly enhanced in these starved larvae,
      indicating that upon starvation, larvae increased the ecdysteroid production rate
      to enhance the rate of survival.

PMID- 16949602
TI  - Into the heart: the emerging role of the ubiquitin-proteasome system.
AB  - While the role of the ubiquitin-proteasome system (UPS) in regulating cellular
      processes continues to expand, the elucidation of its role in cardiac disease is
      just beginning. The UPS regulates pivotal processes at all levels of cardiac
      biology: from membrane-associated ion channels and receptors to downstream
      signaling intermediates and transcription factors. Moreover, the role of the UPS
      in maintaining cardiac protein quality control is emerging, as exemplified by its
      multiple interactions with the cardiac sarcomere and role in familial
      cardiomyopathies. The diversity of UPS regulation lies in E3 ligases, which
      specifically recognize targets and direct the ubiquitination process. In the
      context of disease, E3 ligase expression affects the severity of disease in both
      ischemia reperfusion injury and cardiac hypertrophy in vivo by modulating
      signaling intermediates. In ischemia-reperfusion injury, the activities of CHIP
      and MDM2 (both with E3 ligase activity) profoundly affect apoptosis regulation
      and severity of disease. In cardiac hypertrophy, Atrogin1 and MuRF1 attenuate
      cardiac hypertrophy by interacting with calcineurin and PKCepsilon, respectively.
      Additionally, MuRF1 and MDM2 interact with sarcomeric proteins (cTnI and Tcap,
      respectively) which may prove to be mechanisms by which hypertrophy is attenuated
      or protein quality modulated. All of these exciting new findings, however, must
      be taken in the context of disease regulation of the UPS components themselves.
      Key UPS components (e.g. ubiquitin, E1, E2, E3, proteasome) are themselves
      transcriptionally regulated in cardiac disease. Our understanding of the precise
      nature by which the UPS regulates key biological functions in cardiac disease has
      just begun.

PMID- 16949603
TI  - The C2 domain of PKCalpha is a Ca2+ -dependent PtdIns(4,5)P2 sensing domain: a
      new insight into an old pathway.
AB  - The C2 domain is a targeting domain that responds to intracellular Ca2+ signals
      in classical protein kinases (PKCs) and mediates the translocation of its host
      protein to membranes. Recent studies have revealed a new motif in the C2 domain,
      named the lysine-rich cluster, that interacts with acidic phospholipids. The
      purpose of this work was to characterize the molecular mechanism by which
      PtdIns(4,5)P2 specifically interacts with this motif. Using a combination of
      isothermal titration calorimetry, fluorescence resonance energy transfer and time
      lapse confocal microscopy, we show here that Ca2+ specifically binds to the Ca2+ 
      binding region, facilitating PtdIns(4,5)P2 access to the lysine-rich cluster. The
      magnitude of PtdIns(4,5)P2 binding is greater than in the case of other
      polyphosphate phosphatidylinositols. Very importantly, the residues involved in
      PtdIns(4,5)P2 binding are essential for the plasma membrane localization of
      PKCalpha when RBL-2H3 cells are stimulated through their IgE receptors.
      Additionally, CFP-PH and CFP-C1 domains were used as bioprobes to demonstrate the
      co-existence of PtdIns(4,5)P2 and diacylglycerol in the plasma membrane, and it
      was shown that although a fraction of PtdIns(4,5)P2 is hydrolyzed to generate
      diacylglycerol and IP3, an important amount still remains in the membrane where
      it is available to activate PKCalpha. These findings entail revision of the
      currently accepted model of PKCalpha recruitment to the membrane and its
      activation.

PMID- 16949604
TI  - Heteronuclear NMR identifies a nascent helix in intrinsically disordered dynein
      intermediate chain: implications for folding and dimerization.
AB  - The intermediate chain of dynein forms a tight subcomplex with dimeric light
      chains LC8 and Tctex-1, and together they constitute the cargo attachment
      complex. There is considerable interest in identifying the role of these light
      chains in the assembly of the two copies of the intermediate chain. The N
      terminal domain of the intermediate chain, IC1-289, contains the binding sites
      for the light chains, and is a highly disordered monomer but gains helical
      structure upon binding to light chains LC8 and Tctex-1. To provide insights into
      the structural and dynamic changes that occur in the intermediate chain upon
      light chains binding, we have used NMR spectroscopy to compare the properties of
      two distinct sub-domains of IC1-289: IC84-143 which is the light chains binding
      domain, and IC198-237, which contains a predicted coiled coil necessary for the
      increase in ordered structure upon light chain binding. Neither construct has
      stable secondary structure when probed by circular dichroism and amide chemical
      shift dispersion. Specific residues of IC84-143 involved in binding to the light
      chains were identified by their increase in resonance line broadening and the
      corresponding large intensity reduction in 1H-15N HSQC spectra. Interestingly,
      IC84-143 shows no sign of structure formation after binding to either LC8 or
      Tctex-1 or to both. IC198-237, on the other hand, contains a population of a
      nascent helix at low temperature as identified by heteronuclear NMR relaxation
      measurements, secondary chemical shifts, and sequential amide-amide
      connectivities. These data are consistent with a model for light chain binding
      coupled to intermediate chain dimerization through forming a coiled coil distant
      from the binding site.

PMID- 16949605
TI  - Direct visualization of saposin remodelling of lipid bilayers.
AB  - Saposins A, B, C and D are soluble, non-enzymatic proteins that interact with
      lysosomal membranes to activate the breakdown and transfer of glycosphingolipids.
      The mechanisms of hydrolase activation and lipid transfer by saposins remain
      unknown. We have used in situ atomic force microscopy (AFM) with simultaneous
      confocal fluorescence microscopy to investigate the interactions of saposins with
      lipid membranes. AFM images of the effect of saposins A, B and C on supported
      lipid bilayers showed a time and concentration-dependent nucleated spread of
      membrane transformation. Saposin B produced deep gaps that ultimately filled with
      granular material, while saposins A and C lead to localized areas of membrane
      that were reduced in height by approximately 1.5 nm. Fluorescence-labeled saposin
      C co-localized with the transformed areas of the bilayer, indicating stable
      binding to the membrane. Fluorescence resonance energy transfer confirmed a
      direct interaction between saposin C and lipid. Under certain conditions of
      membrane lipid composition and saposin concentration, extensive bilayer lipid
      removal was observed. We propose a multi-step mechanism that integrates the
      structural features and amphipathic properties of the saposin proteins.

PMID- 16949606
TI  - Computational studies of tryptophanyl-tRNA synthetase: activation of ATP by
      induced-fit.
AB  - Catalysis of amino acid activation by Bacillus stearothermophilus tryptophanyl
      tRNA synthetase involves three allosteric states: (1) Open; (2) closed pre
      transition state (PreTS); and (3) closed products (Product). The interconversions
      of these states entail significant domain motions driven by ligand binding. We
      explore the application of molecular dynamics simulations to investigate ligand
      linked conformational stability changes associated with this catalytic cycle.
      Multiple molecular dynamics trajectories (5 ns) for 11 distinct liganded and
      unliganded monomer configurations show that the PreTS conformation is unstable in
      the absence of ATP, reverting within approximately 600 ps nearly to the Open
      conformation. In contrast, Open and Product state trajectories were stable, even
      without ligands, confirming the previous suggestion that catalysis entails
      destabilization of the protein conformation, driven by ATP-binding energies
      developed as the PreTS state assembles during induced-fit. The simulations
      suggest novel mechanistic details associated with both induced-fit (Open-PreTS)
      and catalysis (PreTS-Product). Notably, Mg2+ -ATP interactions are coupled to
      interactions between ATP and active-site lysine side-chains via mechanisms that
      cannot be captured under the molecular mechanics approximations, and which
      therefore require restraining potentials for stable simulation. Simulations of
      Mg2+. ATP-bound PreTS complexes with restraining potentials and with a virtual
      K111A mutant confirm that these coupling interactions are necessary to sustain
      the PreTS conformation and, in turn, provide a new model for how the PreTS
      conformation activates ATP for catalysis. These results emphasize the central
      role of the PreTS state as a high-energy intermediate structure along the
      catalytic pathway and suggest that Mg2+ and the KMSKS loop function cooperatively
      during catalysis.

PMID- 16949607
TI  - Subcellular localization of interacting proteins by bimolecular fluorescence
      complementation in planta.
AB  - Bimolecular fluorescence complementation (BiFC) represents one of the most
      advanced and powerful tools for studying and visualizing protein-protein
      interactions in living cells. In this method, putative interacting protein
      partners are fused to complementary non-fluorescent fragments of an
      autofluorescent protein, such as the yellow spectral variant of the green
      fluorescent protein. Interaction of the test proteins may result in
      reconstruction of fluorescence if the two portions of yellow spectral variant of
      the green fluorescent protein are brought together in such a way that they can
      fold properly. BiFC provides an assay for detection of protein-protein
      interactions, and for the subcellular localization of the interacting protein
      partners. To facilitate the application of BiFC to plant research, we designed a
      series of vectors for easy construction of N-terminal and C-terminal fusions of
      the target protein to the yellow spectral variant of the green fluorescent
      protein fragments. These vectors carry constitutive expression cassettes with an
      expanded multi-cloning site. In addition, these vectors facilitate the assembly
      of BiFC expression cassettes into Agrobacterium multi-gene expression binary
      plasmids for co-expression of interacting partners and additional autofluorescent
      proteins that may serve as internal transformation controls and markers of
      subcellular compartments. We demonstrate the utility of these vectors for the
      analysis of specific protein-protein interactions in various cellular
      compartments, including the nucleus, plasmodesmata, and chloroplasts of different
      plant species and cell types.

PMID- 16949608
TI  - Two parts of the T3S4 domain of the hook-length control protein FliK are
      essential for the substrate specificity switching of the flagellar type III
      export apparatus.
AB  - The switch in export specificity of the type III flagellar protein export
      apparatus from rod/hook type to filament type is believed to occur upon
      completion of hook assembly by way of an interaction of the type III secretion
      substrate specificity switch (T3S4) domain of the hook-length control protein
      FliK, with the integral membrane export apparatus component FlhB. The T3S4 domain
      of FliK (FliKT3S4) consisting of amino acid residues 265-405 has an unstable and
      flexible conformation in its last 35 residues (FliKCT). To investigate the role
      of FliKT3S4 in substrate specificity switching, we studied the effect of
      deletions and point mutations within this domain and characterized suppressor
      mutations. Deletions of ten amino acid residues within the region of residues 301
      350 and five amino acids of residues 401-405 abolished switching of export
      specificity. Site directed mutagenesis showed that highly conserved residues,
      Val302, Ile304, Leu335, Val401 and Ala405, are essential, and that the five C
      terminal residues (401-405) are restricted in conformation for the switching
      process. Suppressor mutant analysis of the fliK(S319Y) mutant, which produces
      extended hooks with filaments attached due to delayed switching, suggested that
      FliKT3S4 interacts with the C terminal half of the cytoplasmic domain of FlhB
      (FlhBC). We propose a two step binding model of FliKT3S4 and FlhBC, in which
      residues 301-350 of FliK bind to FlhBC upon hook assembly completion at about 55
      nm, and then unfolded FliKCT binds to FlhBC to trigger the switch in substrate
      specificity.

PMID- 16949609
TI  - Mechanism of oligomerisation of cyclase-associated protein from Dictyostelium
      discoideum in solution.
AB  - Cyclase-associated protein (CAP) is a highly conserved modular protein implicated
      in the regulation of actin filament dynamics and a variety of developmental and
      morphological processes. The protein exists as a high molecular weight complex in
      cell extracts and purified protein possesses a high tendency to aggregate, a
      major obstacle for crystallisation. Using a mutagenesis approach, we show that
      two structural features underlie the mechanism of oligomerisation in
      Dictyostelium discoideum CAP. Positively charged clusters on the surface of the N
      terminal helix-barrel domain are involved in inter-molecular interactions with
      the N or C-terminal domains. Abolishing these interactions mainly renders dimers
      due to a domain swap feature in the extreme C-terminal region of the protein that
      was previously described. Based on earlier studies with yeast CAP, we also
      generated constructs with mutations in the extreme N-terminal region of
      Dictyostelium CAP that did not show significantly altered oligomerisation
      behaviour. Constructs with mutations in the earlier identified protein-protein
      interaction interface on the N-terminal domain of CAP could not be expressed as
      soluble protein. Assessment of the soluble proteins indicates that the mutations
      did not affect their overall fold. Further studies point to the correlation
      between stability of full-length CAP with its multimerisation behaviour, where
      oligomer formation leads to a more stable protein.

PMID- 16949610
TI  - Assembly of the archaeal box C/D sRNP can occur via alternative pathways and
      requires temperature-facilitated sRNA remodeling.
AB  - Archaeal dual-guide box C/D small nucleolar RNA-like RNAs (sRNAs) bind three core
      proteins in sequential order at both terminal box C/D and internal C'/D' motifs
      to assemble two ribonuclear protein (RNP) complexes active in guiding nucleotide
      methylation. Experiments have investigated the process of box C/D sRNP assembly
      and the resultant changes in sRNA structure or "remodeling" as a consequence of
      sRNP core protein binding. Hierarchical assembly of the Methanocaldococcus
      jannaschii sR8 box C/D sRNP is a temperature-dependent process with binding of L7
      and Nop56/58 core proteins to the sRNA requiring elevated temperature to
      facilitate necessary RNA structural dynamics. Circular dichroism (CD)
      spectroscopy and RNA thermal denaturation revealed an increased order and
      stability of sRNA folded structure as a result of L7 binding. Subsequent binding
      of the Nop56/58 and fibrillarin core proteins to the L7-sRNA complex further
      remodeled sRNA structure. Assessment of sR8 guide region accessibility using
      complementary RNA oligonucleotide probes revealed significant changes in guide
      region structure during sRNP assembly. A second dual-guide box C/D sRNA from M.
      jannaschii, sR6, also exhibited RNA remodeling during temperature-dependent sRNP
      assembly, although core protein binding was affected by sR6's distinct folded
      structure. Interestingly, the sR6 sRNP followed an alternative assembly pathway,
      with both guide regions being continuously exposed during sRNP assembly. Further
      experiments using sR8 mutants possessing alternative guide regions demonstrated
      that sRNA folded structure induced by specific guide sequences impacted the sRNP
      assembly pathway. Nevertheless, assembled sRNPs were active for sRNA-guided
      methylation independent of the pathway followed. Thus, RNA remodeling appears to
      be a common and requisite feature of archaeal dual-guide box C/D sRNP assembly
      and formation of the mature sRNP can follow different assembly pathways in
      generating catalytically active complexes.

PMID- 16949611
TI  - Mis-translation of a computationally designed protein yields an exceptionally
      stable homodimer: implications for protein engineering and evolution.
AB  - We recently used computational protein design to create an extremely stable,
      globular protein, Top7, with a sequence and fold not observed previously in
      nature. Since Top7 was created in the absence of genetic selection, it provides a
      rare opportunity to investigate aspects of the cellular protein production and
      surveillance machinery that are subject to natural selection. Here we show that a
      portion of the Top7 protein corresponding to the final 49 C-terminal residues is
      efficiently mis-translated and accumulates at high levels in Escherichia coli. We
      used circular dichroism, size-exclusion chromatography, small-angle X-ray
      scattering, analytical ultra-centrifugation, and NMR spectroscopy to show that
      the resulting C-terminal fragment (CFr) protein adopts a compact, extremely
      stable, homo-dimeric structure. Based on the solution structure, we engineered an
      even more stable variant of CFr by disulfide-induced covalent circularisation
      that should be an excellent platform for design of novel functions. The
      accumulation of high levels of CFr exposes the high error rate of the protein
      translation machinery. The rarity of correspondingly stable fragments in natural
      proteins coupled with the observation that high quality ribosome binding sites
      are found to occur within E. coli protein-coding regions significantly less often
      than expected by random chance implies a stringent evolutionary pressure against
      protein sub-fragments that can independently fold into stable structures. The
      symmetric self-association between two identical mis-translated CFr sub-domains
      to generate an extremely stable structure parallels a mechanism for natural
      protein-fold evolution by modular recombination of protein sub-structures.

PMID- 16949612
TI  - Crystal structure of osmoporin OmpC from E. coli at 2.0 A.
AB  - Porins form transmembrane pores in the outer membrane of Gram-negative bacteria
      with matrix porin OmpF and osmoporin OmpC from Escherichia coli being
      differentially expressed depending on environmental conditions. The three
      dimensional structure of OmpC has been determined to 2.0 A resolution by X-ray
      crystallography. As expected from the high sequence similarity, OmpC adopts the
      OmpF-like 16-stranded hollow beta-barrel fold with three beta-barrels associated
      to form a tight trimer. Unlike in OmpF, the extracellular loops form a continuous
      wall at the perimeter of the vestibule common to the three pores, due to a 14
      residues insertion in loop L4. The pore constriction and the periplasmic outlet
      are very similar to OmpF with 74% of the pore lining residues being conserved.
      Overall, only few ionizable residues are exchanged at the pore lining. The OmpC
      structure suggests that not pore size, but electrostatic pore potential and
      particular atomic details of the pore linings are the critical parameters that
      physiologically distinguish OmpC from OmpF.

PMID- 16949613
TI  - Electron tomography of swollen rigor fibers of insect flight muscle reveals a
      short and variably angled S2 domain.
AB  - Subfragment 2 (S2), the segment that links the two myosin heads to the thick
      filament backbone, may serve as a swing-out adapter allowing crossbridge access
      to actin, as the elastic component of crossbridges and as part of a
      phosphorylation-regulated on-off switch for crossbridges in smooth muscle. Low
      salt expansion increases interfilament spacing (from 52 nm to 67 nm) of rigor
      insect flight muscle fibers and exposes a tethering segment of S2 in many
      crossbridges. Docking an actoS1 atomic model into EM tomograms of swollen rigor
      fibers identifies in situ for the first time the location, length and angle
      assignable to a segment of S2. Correspondence analysis of 1831 38.7 nm
      crossbridge repeats grouped self-similar forms from which class averages could be
      computed. The full range of the variability in angles and lengths of exposed S2
      was displayed by using class averages for atomic fittings of acto-S1, while S2
      was modeled by fitting a length of coiled-coil to unaveraged individual repeats.
      This hybrid modeling shows that the average length of S2 tethers along the thick
      filament (except near the tapered ends) is approximately 10 nm, or 16% of S2's
      total length, with an angular range encompassing 90 degrees axially and 120
      degrees azimuthally. The large range of S2 angles indicates that some rigor
      bridges produce positive force that must be balanced by others producing drag
      force. The short tethering segment clarifies constraints on the function of S2 in
      accommodating variable myosin head access to actin. We suggest that the short
      length of S2 may also favor intermolecular head-head interactions in IFM relaxed
      thick filaments.

PMID- 16949615
TI  - Crystal structures of the AppA BLUF domain photoreceptor provide insights into
      blue light-mediated signal transduction.
AB  - Proteins containing a sensor of blue light using FAD (BLUF) domain control
      diverse cellular processes, such as gene expression, nucleotide metabolism and
      motility, by relaying blue light signals to distinct output units. Despite its
      crucial and widespread functions, the mechanism of BLUF signal transduction has
      remained elusive. We determined crystal structures of the dark-adapted state and
      of a photo-excited, red-shifted photocycle intermediate of the BLUF unit of AppA,
      a purple bacterial photoreceptor involved in the light-dependent regulation of
      photosynthesis gene expression. In contrast to a recently published crystal
      structure of the AppA BLUF domain determined in the presence of detergent
      molecules, our structural model of the dark state corresponds well to those
      reported for the BLUF domains of Tll0078 and BlrB. This establishes that a highly
      conserved methionine (Met106 in AppA) is next to the active site glutamine (Gln63
      in AppA), which is of relevance for the latter's orientation in the dark state
      and for the mechanism of the photoreaction. The comparison of the dark-adapted
      and photointermediate state structures shows light-induced conformational
      alterations, which suggest a path for signal propagation. In particular, we
      observe a significant movement of the Met106 side-chain. Met106 thereby changes
      its mode of interaction with Gln63, which supports a light-dependent rotation of
      the latter. In view of other BLUF structures available, our data further suggest
      that the hydrogen bond between Asn45 and the backbone carbonyl of His105 breaks
      upon illumination. The ensuing extensive structural rearrangement of beta-strand
      5 is predicted to involve a flip of Met106 out of the flavin-binding pocket and
      Trp104 moving in to fill the void. We propose that the blue light signal is
      transmitted towards the surface of the BLUF domain via His44, which serves as a
      reporter of active site changes.

PMID- 16949614
TI  - A counterintuitive Mg2+-dependent and modification-assisted functional folding of
      mitochondrial tRNAs.
AB  - Mitochondrial tRNAs (mtRNAs) often lack domains and posttranscriptional
      modifications that are found in cytoplasmic tRNAs. These structural and chemical
      elements normally stabilize the folding of cytoplasmic tRNAs into canonical
      structures that are competent for aminoacylation and translation. For example,
      the dihydrouridine (D) stem and loop domain is involved in the tertiary structure
      of cytoplasmic tRNAs through hydrogen bonds and a Mg2+ bridge to the
      ribothymidine (T) stem and loop domain. These interactions are often absent in
      mtRNA because the D-domain is truncated or missing. Using gel mobility shift
      analyses, UV, circular dichroism and NMR spectroscopies and aminoacylation
      assays, we have investigated the functional folding interactions of chemically
      synthesized and site-specifically modified mitochondrial and cytoplasmic tRNAs.
      We found that Mg2+ is critical for folding of the truncated D-domain of bovine
      mtRNAMet with the tRNA's T-domain. Contrary to the expectation that Mg2+
      stabilizes RNA folding, the mtRNAMet D-domain structure was unfolded and relaxed,
      rather than stabilized in the presence of Mg2+. Because the D-domain is
      transcribed prior to the T-domain, we conclude that Mg2+ prevents misfolding of
      the 5'-half of bovine mtRNAMet facilitating its correct interaction with the T
      domain. The interaction of the mtRNAMet D-domain with the T-domain was enhanced
      by a pseudouridine located in either the D or T-domains compared to that of the
      unmodified RNAs (Kd=25.3, 24.6 and 44.4 microM, respectively). Mg2+ also affected
      the folding interaction of a yeast mtRNALeu1, but had minimal effect on the
      folding of an Escherichia coli cytoplasmic tRNALeu. The D-domain modification,
      dihydrouridine, facilitated mtRNALeu folding. These data indicate that conserved
      modifications assist and stabilize the formation of the functional mtRNA tertiary
      structure.

PMID- 16949616
TI  - Synergism between halide binding and proton transport in a CLC-type exchanger.
AB  - The Cl-/H+ exchange-transporter CLC-ec1 mediates stoichiometric transmembrane
      exchange of two Cl- ions for one proton. A conserved tyrosine residue, Y445,
      coordinates one of the bound Cl- ions visible in the structure of this protein
      and is located near the intersection of the Cl- and H+ pathways. Mutants of this
      tyrosine were scrutinized for effects on the coupled transport of Cl- and H+
      determined electrophysiologically and on protein structure determined
      crystallographically. Despite the strong conservation of Y445 in the CLC family,
      substitution of F or W at this position preserves wild-type transport behavior.
      Substitution by A, E, or H, however, produces uncoupled proteins with robust Cl-
      transport but greatly impaired movement of H+. The obligatory 2 Cl-/1 H+
      stoichiometry is thus lost in these mutants. The structures of all the mutants
      are essentially identical to wild-type, but apparent anion occupancy in the Cl-
      binding region correlates with functional H+ coupling. In particular, as
      determined by anomalous diffraction in crystals grown in Br-, an
      electrophysiologically competent Cl- analogue, the well-coupled transporters show
      strong Br- electron density at the "inner" and "central" Cl- binding sites.
      However, in the uncoupled mutants, Br- density is absent at the central site,
      while still present at the inner site. An additional mutant, Y445L, is
      intermediate in both functional and structural features. This mutant clearly
      exchanges H+ for Cl-, but at a reduced H+-to-Cl- ratio; likewise, both the
      central and inner sites are occupied by Br-, but the central site shows lower Br-
      density than in wild-type (or in Y445F,W). The correlation between proton
      coupling and central-site occupancy argues that halide binding to the central
      transport site somehow facilitates movement of H+, a synergism that is not
      readily understood in terms of alternating-site antiport schemes.

PMID- 16949617
TI  - Expression of distinct classes of titin isoforms in striated and smooth muscles
      by alternative splicing, and their conserved interaction with filamins.
AB  - While the role of titin as a sarcomeric protein is well established, its
      potential functional role(s) in smooth muscles and non-muscle tissues are
      controversial. We used a titin exon array to search for which part(s) of the
      human titin transcriptional unit encompassing 363 exons is(are) expressed in non
      striated muscle tissues. Expression profiling of adult smooth muscle tissues
      (aorta, bladder, carotid, stomach) identified alternatively spliced titin
      isoforms, encompassing 80 to about 100 exons. These exons code for parts of the
      titin Z-disk, I-band and A-band regions, allowing the truncated smooth muscle
      titin isoform to link Z-disks/dense bodies together with thick filaments.
      Consistent with the array data, Western blot studies detected the expression of
      approximately 1 MDa smooth muscle titin in adult smooth muscles, reacting with
      selected Z-disc, I-band, and A-band titin antibodies. Immunofluorescence with
      these antibodies located smooth muscle titin in the cytoplasm of cultured human
      aortic smooth muscle cells and in the tunica media of intact adult bovine aorta.
      Real time PCR studies suggested that smooth muscle titins are expressed from a
      promoter located 35 kb or more upstream of the transcription initiation site used
      for striated muscle titin, driving expression of a bi-cistronic mRNA, coding 5'
      for the anonymous gene FL39502, followed 3' by titin, respectively. Our work
      showed that smooth muscle and striated muscle titins share in their conserved
      amino-terminal regions binding sites for alpha-actinin and filamins: Yeast two
      hybrid screens using Z2-Zis1 titin baits identified prey clones coding for alpha
      actinin-1 and filamin-A from smooth muscle, and alpha-actinin-2/3, filamin-C, and
      nebulin from skeletal muscle cDNA libraries, respectively. This suggests that the
      titin Z2-Zis1 domain can link filamins and alpha-actinin together in the
      periphery of the Z-line/dense bodies in a fashion that is conserved in smooth and
      striated muscles.

PMID- 16949618
TI  - Mathematical analysis of trabecular 'trajectories' in apparent trajectorial
      structures: the unfortunate historical emphasis on the human proximal femur.
AB  - Wolff's "law" of the functional adaptation of bone is rooted in the trajectory
      hypothesis of cancellous bone architecture. Wolff often used the human proximal
      femur as an example of a trajectorial structure (i.e. arched trabecular patterns
      appear to be aligned along tension/compression stress trajectories). We examined
      two tenets of the trajectory hypothesis; namely, that the trabecular tracts from
      the tension- and compression-loaded sides of a bending environment will: (1)
      follow 'lines' (trajectories) of tension/compression stress that resemble an arch
      with its apex on a neutral axis, and (2) form orthogonal (90 degrees )
      intersections. These predictions were analysed in proximal femora of chimpanzees
      and modern humans, and in calcanei of sheep and deer. Compared to complex loading
      of the human femoral neck, the chimpanzee femoral neck reputedly receives
      relatively simpler loading (i.e. temporally/spatially more consistent bending),
      and the artiodactyl calcaneus is even more simply loaded in bending. In order to
      directly consider Wolff's observations, measurements were also made on two
      dimensional, cantilevered beams and curved beams, each with intersecting
      compression/tension stress trajectories. Results in the calcanei showed: (1) the
      same nonlinear equation best described the dorsal ("compression") and plantar
      ("tension") trabecular tracts, (2) these tracts could be exactly superimposed on
      the corresponding compression/tension stress trajectories of the cantilevered
      beams, and (3) trabecular tracts typically formed orthogonal intersections. In
      contrast, trabecular tracts in human and chimpanzee femoral necks were non
      orthogonal (mean approximately 70 degrees ), with shapes differing from
      trabecular tracts in calcanei and stress trajectories in the beams. Although
      often being described by the same equations, the trajectories in the curved beams
      had lower r(2) values than calcaneal tracts. These results suggest that the
      trabecular patterns in the calcanei and stress trajectories in short beams are
      consistent with basic tenets of the trajectory hypothesis while those in human
      and chimpanzee femoral necks are not. Compared to calcanei, the more complexly
      loaded human and chimpanzee femoral necks probably receive more
      prevalent/predominant shear, which is best accommodated by non-orthogonal,
      asymmetric trabecular tracts. The asymmetrical trabecular patterns in the
      proximal femora may also reflect the different developmental 'fields'
      (trochanteric vs. neck/head) that formed these regions, of which there is no
      parallel in the calcanei.

PMID- 16949619
TI  - Optimal flight initiation distance.
AB  - Decisions regarding flight initiation distance have received scant theoretical
      attention. A graphical model by Ydenberg and Dill (1986. The economics of fleeing
      from predators. Adv. Stud. Behav. 16, 229-249) that has guided research for the
      past 20 years specifies when escape begins. In the model, a prey detects a
      predator, monitors its approach until costs of escape and of remaining are equal,
      and then flees. The distance between predator and prey when escape is initiated
      (approach distance = flight initiation distance) occurs where decreasing cost of
      remaining and increasing cost of fleeing intersect. We argue that prey fleeing as
      predicted cannot maximize fitness because the best prey can do is break even
      during an encounter. We develop two optimality models, one applying when all
      expected future contribution to fitness (residual reproductive value) is lost if
      the prey dies, the other when any fitness gained (increase in expected RRV)
      during the encounter is retained after death. Both models predict optimal flight
      initiation distance from initial expected fitness, benefits obtainable during
      encounters, costs of escaping, and probability of being killed. Predictions match
      extensively verified predictions of Ydenberg and Dill's (1986) model. Our main
      conclusion is that optimality models are preferable to break-even models because
      they permit fitness maximization, offer many new testable predictions, and allow
      assessment of prey decisions in many naturally occurring situations through
      modification of benefit, escape cost, and risk functions.

PMID- 16949620
TI  - Zinc L-carnosine protects colonic mucosal injury through induction of heat shock
      protein 72 and suppression of NF-kappaB activation.
AB  - In this study, we investigated the effects of zinc L-carnosine, an anti-ulcer
      drug, on acetic acid-induced colonic mucosal injury and the correlation of these
      effects with expression of 72-kDa heat shock proteins (HSP72) and nuclear factor
      kappa B (NF-kappaB) activation in rat colonic mucosa in vivo. After intrarectal
      administration of zinc L-carnosine, the rats received intrarectal infusion of 5%
      acetic acid (1 ml). The colonic mucosal damage was evaluated by macroscopic
      assessments 24 h after the intrarectal infusion of acetic acid. Expression of
      HSP72 in rat colonic mucosa was evaluated by Western blot analysis before and
      after zinc L-carnosine administration. NF-kappaB activation was evaluated by
      electrophoretic mobility shift assays (EMSA). Zinc L-carnosine inhibited visible
      damage in rat colonic mucosa by acetic acid. Expression of HSP72 was
      significantly increased at 6 h after zinc L-carnosine administration.
      Furthermore, NF-kappaB activation in colonic mucosa was suppressed 6 h after zinc
      L-carnosine treatment. These results suggested that zinc L-carnosine protects the
      colonic mucosa against acetic acid by induction of HSP72 and suppression of NF
      kappaB activation and zinc L-carnosine may be a novel therapeutic agent for the
      therapy of inflammatory bowel disease.

PMID- 16949621
TI  - Binge administration of 3,4-methylenedioxymethamphetamine ("ecstasy") impairs the
      survival of neural precursors in adult rat dentate gyrus.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA) is a potent stimulant and hallucinogenic
      drug whose ability to regulate neurogenesis in the adult has not been previously
      investigated. We used 5'-bromo-2-deoxyuridine (BrdU) and Ki-67 as mitotic
      markers, and doublecortin (DCX) as a marker of immature neurons, to study
      proliferation, survival and maturation of adult-generated cells in the dentate
      gyrus (DG) of the hippocampus following binge administration of MDMA (8
      injections of 5 mg/kg at 6 h intervals). The results showed that MDMA treatment
      did not affect cytogenesis in the DG, but significantly decreased the survival
      rate of cells incorporated after 2 weeks to the granular layer of the DG by ca.
      50%, and of those remaining in the subgranular layer by ca. 30%. Two weeks after
      exposure to MDMA the length of dendritic arbors and the number of dendritic
      branches of immature DCX+ neurons were nearly identical to those of control rats,
      as was the level of colocalization of BrdU with DCX. These results demonstrate
      that binge MDMA administration does not affect the proliferation rates of
      progenitor cells in the DG, but has deleterious effects on adult neurogenesis by
      impairing the short-term survival of vulnerable neural precursors.

PMID- 16949622
TI  - CP-809,101, a selective 5-HT2C agonist, shows activity in animal models of
      antipsychotic activity.
AB  - CP-809,101 is a potent, functionally selective 5-HT(2C) agonist that displays
      approximately 100% efficacy in vitro. The aim of the present studies was to
      assess the efficacy of a selective 5-HT(2C) agonist in animal models predictive
      of antipsychotic-like efficacy and side-effect liability. Similar to currently
      available antipsychotic drugs, CP-809,101 dose-dependently inhibited conditioned
      avoidance responding (CAR, ED(50)=4.8 mg/kg, sc). The efficacy of CP-809,101 in
      CAR was completely antagonized by the concurrent administration of the 5-HT(2C)
      receptor antagonist, SB-224,282. CP-809,101 antagonized both PCP- and d
      amphetamine-induced hyperactivity with ED(50) values of 2.4 and 2.9 mg/kg (sc),
      respectively and also reversed an apomorphine induced-deficit in prepulse
      inhibition. At doses up to 56 mg/kg, CP-809,101 did not produce catalepsy. Thus,
      the present results demonstrate that the 5-HT(2C) agonist, CP-809,101, has a
      pharmacological profile similar to that of the atypical antipsychotics with low
      extrapyramidal symptom liability. CP-809,101 was inactive in two animal models of
      antidepressant-like activity, the forced swim test and learned helplessness.
      However, CP-809,101 was active in novel object recognition, an animal model of
      cognitive function. These data suggest that 5-HT(2C) agonists may be a novel
      approach in the treatment of psychosis as well as for the improvement of
      cognitive dysfunction associated with schizophrenia.

PMID- 16949623
TI  - A nerve growth factor-induced retrograde survival signal mediated by mechanisms
      downstream of TrkA.
AB  - Considerable evidence suggests that mammalian neurons are always poised to
      destroy themselves by apoptosis but are blocked by retrograde survival signals
      triggered in their axon terminals by neurotrophic factors secreted by the target
      cells they innervate. Studies with nerve growth factor (NGF) and its receptor,
      TrkA, form the basis of the prevalent theory of retrograde signaling. According
      to this theory, retrograde survival signals travel to the cell bodies in the form
      of endosomes produced at the axon terminals with internalized NGF in their lumens
      bound to phosphorylated TrkA in their membranes. The inhibition of TrkA
      phosphorylation in the cell bodies of sympathetic neurons in compartmented
      cultures by K252a blocked retrograde NGF signaling in some studies in accord with
      this theory, but other studies do not show a block. We report that local block of
      TrkA phosphorylation in the cell bodies and proximal axons with another kinase
      inhibitor, Go6976 (25nM), did not block the survival signal from NGF at distal
      axons, while Go6976 at the distal axons completely blocked the retrograde
      survival signal. These results suggest that downstream signals activated by
      phosphorylated TrkA in the distal axons carry the retrograde survival signals to
      the cell bodies, possibly via a downstream type of signaling endosome not
      necessarily transporting NGF or phosphorylated TrkA. Unlike Go6976, K252a exerted
      a survival effect on its own when applied to cell bodies/proximal axons or distal
      axons of completely NGF-deprived neurons. The latter effect suggests that
      downstream retrograde survival signals can arise from alterations in one or more
      kinase activities in the distal axons without activation of TrkA by NGF.

PMID- 16949624
TI  - LTP and adaptation to inactivity: overlapping mechanisms and implications for
      metaplasticity.
AB  - LTP and other rapidly induced forms of synaptic modification tune individual
      synaptic weights, whereas slower forms of plasticity such as adaptation to
      inactivity are thought to keep neurons within their firing limits and preserve
      their capability for information processing. Here we describe progress in
      understanding the relationship between LTP and adaptation to inactivity. A
      prevailing view is that adaptation to inactivity is purely postsynaptic, scales
      synaptic strength uniformly across all synapses, and thus preserves relative
      synaptic weights without interfering with signatures of prior LTP or the relative
      capacity for future LTP. However, recent evidence in hippocampal neurons
      indicates that, like LTP, adaptation to AMPA receptor blockade can draw upon a
      repertoire of synaptic expression mechanisms including enhancement of presynaptic
      vesicular turnover and increased quantal amplitude mediated by recruitment of
      homomeric GluR1 AMPA receptors. These pre- and postsynaptic changes appeared
      coordinated and preferentially expressed at subset of synapses, thereby
      increasing the variability of miniature EPSCs. In contrast to the NMDA receptor-,
      Ca2+ entry-dependent induction of LTP, adaptation to inactivity may be mediated
      by attenuation of voltage-sensitive L-type Ca2+ channel function. The associated
      intracellular signaling involves elevation of betaCaMKII, which in turn
      downregulates alphaCaMKII, a key player in LTP. Thus, adaptation to inactivity
      and LTP are not strictly independent with regard to mechanisms of signaling and
      expression. Indeed, we and others have found that responses to LTP-inducing
      stimuli can be sharply altered by prior inactivity, suggesting that the slow
      adaptation changes the rules of plasticity-an interesting example of
      "metaplasticity".

PMID- 16949625
TI  - Using registries in general practice to estimate countrywide morbidity in The
      Netherlands.
AB  - OBJECTIVE: Examining the possibility of using data from registries in general
      practice in order to present morbidity figures concerning a broad range of major
      diseases for the Dutch population. STUDY DESIGN: Qualitative and quantitative
      analysis of registered diagnoses. METHODS: Quantitative data from six registries
      were obtained. In addition, information about the registration process was
      obtained and discussed with representatives of the registries. Subjects for
      discussion were the general characteristics of the registries and disease
      specific rules. RESULTS: Some important differences exist in the characteristics
      of the registries and the disease-specific coding rules for computing incidence
      and prevalence. However, for most diseases the rules of two or more registries
      corresponded with each other, so that a selection of registries that measured the
      occurrence of a particular disease in a similar way could be made. Nevertheless,
      for some age categories rather large differences between registries were
      observed. The best estimates for the whole country were calculated as the average
      incidence and prevalence of the selected registries. CONCLUSIONS: Data that were
      originally obtained during patient care can be made usable for public health
      policy purposes. To further improve the quality of data and to increase the
      usefulness of these data for public health policy purposes, more efforts are
      required.

PMID- 16949626
TI  - The impact of multiple role occupancy on health-related behaviours in Japan:
      differences by gender and age.
AB  - OBJECTIVES: We examined gender and age differences in the impact of multiple role
      occupancy on health-related behaviours and health status among working age
      Japanese adults. METHODS: We analysed the individually linked, nationally
      representative data of 5693 respondents aged 20-59, who completed the
      Comprehensive Survey of the Living Conditions of People on Health and Welfare and
      the National Nutrition Survey, conducted by the Japanese government in 1995.
      RESULTS: Younger women benefited from multiple roles (less smoking), while
      younger men demonstrated more high-risk behaviours (more smoking, heavier
      drinking). By contrast, middle-aged men benefited from multiple roles (less
      smoking, fewer health problems), while middle-aged women reported lower health
      maintenance behaviours (less exercise, fewer health check-ups). CONCLUSIONS:
      Japanese society appears to be undergoing a transition in gender roles, as
      reflected by age and gender differences in the impact of multiple roles on health
      and health-related behaviours. Middle-aged males benefit from multiple roles
      (being the primary bread-winner and being married), while middle-aged women do
      not. This pattern seems to break down for younger Japanese men and women.

PMID- 16949627
TI  - Staining patterns for actin and villin distinguish M cells in bovine follicle
      associated epithelium.
AB  - M cells play a central role in the initiation of mucosal immune responses.
      However, a primary source of difficulty for investigations of this is the lack of
      an available specific marker for bovine M cells. As M cells possess irregular and
      short microvilli, we investigated the distribution and localization of the
      microvillar proteins actin and villin by immunohistochemistry of the gut of
      calves. In ileum of the calf, actin and villin were clearly and continuously
      immunostained in the brush border of the villous epithelia, however,
      discontinuous immunostaining with patches of no staining were observed in
      follicle-associated epithelium (FAE). Electron microscopy revealed that M cells
      had irregular microvilli and lacked the typical brush border, and it was inferred
      that these patches of no staining might be the intercellular crevices of M cells.
      As the microvilli of M cells were very sparse, there were several areas of weak
      immunostaining in calf jejunal FAE. These results suggest that M cells in calf
      FAE are detectable by the absence of staining for actin and villin.

PMID- 16949628
TI  - Identification of novel proteins induced by estradiol, 4-hydroxytamoxifen and
      acolbifene in T47D breast cancer cells.
AB  - Tamoxifen is currently used as adjuvant therapy for estrogen receptor (ER)
      positive breast cancer patients and as a chemopreventative agent. Although ER is
      a predictive marker for tamoxifen response, ER status fails to predict tamoxifen
      response in a significant number of patients highlighting the need to identify
      new pathways for tamoxifen sensitivity/resistance. To identify novel proteins
      induced by tamoxifen in breast cancer cells sensitive to tamoxifen growth
      inhibition, two-dimensional (2D) gel electrophoresis was used to profile proteins
      in T47D breast cancer cells. Six proteins were identified that were
      differentially regulated by 17beta-estradiol, 4-hydroxytamoxifen and the pure
      antagonist acolbifene (EM-652); calreticulin, synapse associated protein 1
      (SYAP1), CD2 antigen binding protein 2 (CD2BP2), nucleosome assembly protein 1
      like 1 (NAP1L1), d-3-phosphoglycerate dehydrogenase (3-PHGDH) and pyridoxine 5'
      phosphate oxidase (PNPO). At the mRNA level, these ligands differentially
      regulated expression of mRNAs encoding the identified proteins in T47D and MCF7
      cells but had no effect on mRNA in ERalpha-negative MDA-MB-231 breast cancer
      cells. These novel SERM-regulated proteins may participate in new or existing
      pathways for sensitivity or resistance to SERMs.

PMID- 16949629
TI  - A method on calculating high-dimensional mutual information and its application
      to registration of multiple ultrasound images.
AB  - Using mutual information as a criterion for medical image registration, which
      requires no prior segmentation or preprocessing, has been both theoretically and
      practically proved to be an effective method in these years. However, this
      technique is confined in registering two images and hard to apply to multiple
      ones. The reason is that unlike mutual information between two variables, high
      dimensional mutual information is ill defined. In textbooks and theoretical
      essays, three-dimensional mutual information is proposed based on Venn diagram.
      Unfortunately, mutual information defined in this way is not necessarily
      nonnegative. In order to overcome the problem, in this paper, we introduce the
      mutual information matrix. By calculating its eigenvalues, high-dimensional
      mutual information is defined. This definition is nonnegative, bounded, and could
      be extended to higher dimensions, thus enables us to register more than three
      images. In the end, this definition is tested and proved to be effective on
      registration of multiple US images through simulation.

PMID- 16949630
TI  - Microbubble-enhanced hemorrhage control using high intensity focused ultrasound.
AB  - Our objective was to investigate whether hemorrhage control can be achieved
      faster when high-intensity focused ultrasound (HIFU) is applied in the presence
      of ultrasound contrast agents (UCA) as compared to HIFU only application.
      Incisions (3 cm long and 0.5 cm deep) were produced in the livers of anesthetized
      rabbits. UCA Optison (0.18 ml/kg) was injected into the mesenteric vein. A HIFU
      applicator (5.5 MHz, 6800 W/cm2 in situ) was scanned at a rate of 1-2 mm/s in one
      direction over the incision (with multiple passes if needed), until hemostasis
      was achieved. Hemostasis times were 59+/-23 s (n=21) in the presence of Optison
      and 70+/-23 s (n=29) without Optison. The presence of Optison produced on average
      37% reduction in hemostasis times normalized to initial bleeding rates (p<0.05),
      as well as 60% faster formation of the coagulum seal over the incision (p<0.05).
      Gross and histological observations showed similar appearance of HIFU lesions
      produced in the presence of Optison and HIFU lesions produced without Optison.
      Our results suggest potential utility of UCA for increasing efficiency of HIFU
      induced hemostasis of solid organ injuries.

PMID- 16949631
TI  - Concentrations of polybrominated diphenyl ethers in blood serum from New Zealand.
AB  - Polybrominated diphenyl ethers (PBDEs) were measured in samples of human blood
      serum taken from 23 donors in Wellington, New Zealand. Concentrations expressed
      as the sum of congeners 47, 99, 100, 153, 154, and 183 (SigmaPBDE) were - at an
      average of 7.17 ng SigmaPBDE g (lipid)(-1) - within the range reported for human
      tissues in Europe, but lower than in Australia and North America. The most likely
      source of this contamination is considered to be the release of PBDEs from
      imported consumer goods. The congener pattern observed is in line with that
      reported for human tissues outside North America, but shows a lower contribution
      of PBDE 47 to SigmaPBDE than observed in North Americans. No significant (p>0.1)
      differences between concentrations in males and females were detected, and no
      relationship between donor age and SigmaPBDE concentration was observed. One
      donor displayed concentrations that were significantly elevated (i.e. > average
      +2 standard deviations) above those in others in this study.

PMID- 16949632
TI  - Influence of lead acetate on soil microbial biomass and community structure in
      two different soils with the growth of Chinese cabbage (Brassica chinensis).
AB  - A greenhouse pot experiment was conducted to evaluate the impact of different
      concentrations of lead acetate on soil microbial biomass and community structure
      during growth of Chinese cabbage (Brassica chinensis) in two different soils. The
      field soils were used for a small pot, short-term 60-day growth chamber study.
      The soils were amended with different Pb concentrations, ranging from 0 to
      900mgkg(-1) soil. The experimental design was a 2 soilx2 vegetation/non
      vegetationx6 treatments (Pb)x3 replicate factorial experiment. At 60 days the
      study was terminated and soils were analyzed for microbial parameters, namely,
      microbial biomass, basal respiration and PLFAs. The results indicated that the
      application of Pb at lower concentrations (100 and 300mgkg(-1)) as lead acetate
      resulted in a slight increase in soil microbial biomass, whereas Pb
      concentrations >500mgkg(-1) caused an immediate gradual significant decline in
      biomass. However, the degree of impact on soil microbial biomass and basal
      respiration by Pb was related to management (plant vegetation) or the contents of
      clay and organic matter in soils. The profiles of 21 phospholipid fatty acids
      (PLFAs) were used to assess whether observed changes in functional microbial
      parameters were accompanied by changes in the composition of the microbial
      communities after Pb application at 0, 300 and 900mg Pbkg(-1) soil. The results
      of principal component analyses (PCA) indicated that there were significant
      increases in fungi biomarkers of 18:3omega6c, 18:1omega9c and a decrease in
      cy17:0, which is an indicator of gram-negative bacteria for the high levels of Pb
      treatments In a word, soil microbial biomass and community structure, therefore,
      may be sensitive indicators reflecting environmental stress in soil-Pb-plant
      system. However, further studies will be needed to better understand how these
      changes in microbial community structure might actually impact soil microbial
      community function.

PMID- 16949633
TI  - Broad range analysis of endocrine disruptors and pharmaceuticals using gas
      chromatography and liquid chromatography tandem mass spectrometry.
AB  - Endocrine disrupting compounds (EDCs) and pharmaceuticals and personal care
      products (PPCPs) have been globally detected in impacted natural waters. The
      detection of trace quantities of EDCs and PPCPs in the environment is of great
      concern since some of these compounds have known physiological responses at low
      concentrations. EDCs can have a wide range of polarities, acidic and basic
      moieties, and exist in trace quantities, which often requires numerous complex
      extractions, large sample collection volumes, and multiple instrumental analyses.
      A comprehensive method has been developed allowing for the analysis of 58
      potential EDCs in various water matrices using a single solid-phase extraction
      (SPE) of a 1L sample with subsequent analyses using both gas chromatography and
      liquid chromatography, each coupled with tandem mass spectrometry (GC-MS/MS and
      LC-MS/MS). Instrument detection limits ranged between 0.12-7.5 pg with
      corresponding method reporting limits of 1-10 ng l(-1) in water. Recoveries for
      most compounds were between 50% and 112% with good reproducibility (RSD 6-22%).

PMID- 16949634
TI  - Determination of antibiotic compounds in water by on-line SPE-LC/MSD.
AB  - This study attempts to provide an improved approach for the analysis of
      antibiotics, which normally exist at low concentration in complex matrices such
      as receiving streams of wastewater treatment plant discharge. The analytical
      method developed in this study combines an existing pretreatment technique of
      solid-phase extraction (SPE) with liquid chromatography mass spectrometry
      (LC/MSD) through on-line connection. The on-line connection suppressed the target
      loss by keeping the cartridge from drying, which resulted in improvement of the
      recovery and saving of the analytical time. For the on-line solid-phase
      extraction of 10 ml water samples, recoveries were between 74.3% and 116.5% and
      average LOQ was 0.11 microg l(-1) for the sulfonamide antibiotics (SA) and 0.09
      microg l(-1) for the tetracycline antibiotics (TA). Application of the developed
      method for the analysis of fourteen antibiotics revealed that several antibiotics
      were detected at concentrations above the LOQ in ARW. Treated and untreated
      sewage and agricultural wastewater were mostly responsible for the antibiotics
      contamination of the river. Antibiotics were detected at much higher
      concentrations in the agricultural wastewater sample than in the sewage sample,
      implying substantial use of antibiotics in the agricultural industry. Wastewater
      treatment was generally effective in separation of the antibiotics tested in this
      study. The extent of the treatment depended on the type of antibiotics.
      Hydrophobic antibiotics were more effectively separated from the solution than
      hydrophilic antibiotics.

PMID- 16949635
TI  - LC-MS-MS analysis and occurrence of octyl- and nonylphenol, their ethoxylates and
      their carboxylates in Belgian and Italian textile industry, waste water treatment
      plant effluents and surface waters.
AB  - Alkylphenols (APs), alkylphenol ethoxylates (APEOs), ethoxycarboxylate
      metabolites (APECs) and bisphenol A were determined in surface water using solid
      phase extraction (SPE) followed by triple-quadrupole LC-MS-MS. APs were separated
      by LC from APECs using an acetonitrile-water-gradient without the addition of any
      buffer. Nonylphenol ethoxycarboxylates (NPECs) interfere in the detection of
      nonylphenols (NPs) when using an acidic mobile phase, because they produce the
      same MS-MS fragment ions (219>133 and 147). 4n-NP shows the characteristic
      transition 219>106; it is well suited as internal standard. Nonylphenol
      ethoxylates NPE(n)Os (n=1-17) were analysed separately in a second run by
      positive ionization using an ammonium acetate mobile phase. Textile industry
      discharges, the corresponding wastewater treatment plant (WWTP) effluents and the
      receiving rivers in Belgium and Italy were analysed. Among the substances
      investigated, NPE1C and NPE2O exhibited the highest concentrations in the water
      samples, up to 4.5 microg l(-1) NPE1C in a WWTP effluent and 3.6 microg l(-1)
      NPE2O in a river. The highest NP levels were found in the receiving rivers (max.
      2.5 microg l(-1)). The predicted no-effect concentration (PNEC) for NP of 0.33
      microg l(-1) for water species was frequently exceeded in the surface waters
      investigated, suggesting potential adverse effects to the aquatic environment.

PMID- 16949636
TI  - Gene expression analysis and classification of mode of toxicity of polycyclic
      aromatic hydrocarbons (PAHs) in Escherichia coli.
AB  - Escherichia coli is known to respond to certain toxic chemicals through an
      increased expression of various stress genes. In this study, therefore, the
      expression of recA, katG, fabA and grpE genes was used as a representative for
      DNA, oxidative, membrane and protein damage, respectively, after E. coli was
      exposed to different polycyclic aromatic hydrocarbons (PAHs), i.e., phenanthrene,
      naphthalene and benzo[a]pyrene. To accomplish this, the expression levels of
      these four genes were quantified using a real-time RT-PCR analysis when E. coli
      cultures were under stressful conditions, such as those caused by an exposure to
      mitomycin C, hydrogen peroxide and phenol. It was found that the primary toxic
      effect of each chemical is clearly seen when the expression levels of the
      different genes are compared. Tests with the PAHs showed naphthalene and
      benzo[a]pyrene to be genotoxic, while phenanthrene had no clear effect on the
      expression of any of these genes. Based on these results, the effects due to
      these toxic chemicals and the extent of each stress can be evaluated with ease
      using the expression levels of different stress responsive genes.

PMID- 16949637
TI  - Photocatalytic degradation of phenol by visible light-responsive iron-doped TiO2
      and spontaneous sedimentation of the TiO2 particles.
AB  - Fe-doped TiO2 was prepared by the calcination of Fe(x)TiS(2) (x=0, 0.002, 0.005,
      0.008, 0.01) and characterized by X-ray diffraction (XRD), X-ray photoelectron
      spectroscopy (XPS), and UV-visible diffuse reflectance spectra. All the Fe-doped
      TiO2 were composed of an anatase crystal form and showed red shifts to a longer
      wavelength. The activity of the Fe-doped TiO2 for the degradation of phenol was
      investigated by varying the iron content during UV (365nm) and visible light
      (405nm and 436nm) irradiation. The degradation rate depended on the Fe content
      and the Fe-doped TiO2 was responsive to the visible light as well as the elevated
      activity toward UV light. The molar ratio of 0.005 was the optimum for both the
      UV and visible light irradiations. The result was discussed on the basis of the
      balance of the excited electron-hole trap by the doped Fe(3+) and their charge
      recombination on the doped Fe(3+) level. The Fe-doped TiO2 (x=0.005) was more
      active than P25 TiO2 under solar light irradiation. The suspended Fe-doped TiO2
      spontaneously precipitated once the stirring of the reaction mixture was
      terminated.

PMID- 16949638
TI  - Rhizosphere localized cationic peroxidase from barley roots is strongly activated
      by cadmium and correlated with root growth inhibition.
AB  - The activity of Cd-induced POD isozyme isolated from the surface of intact barley
      roots growing under some abiotic stress conditions (toxic metals: Al, Co, Cu, Hg;
      drought, NaCl, extreme temperatures: heat, cold) and compounds activating (2,4-D)
      or inhibiting (SHAM) POD activity as well as H(2)O(2) and H(2)O(2) scavenger
      (DTT) was characterized. Strong Cd concentration-dependent accumulation of one
      cationic POD isozyme was observed on PAGE, which correlated with Cd- and other
      stress induced root growth inhibition. This isoPOD is basic with isoelectric
      point about 9 and its localization is restricted only to the apical part of the
      barley root tip.

PMID- 16949639
TI  - Enzymatic biomarkers in the crab Carcinus maenas from the Minho River estuary (NW
      Portugal) exposed to zinc and mercury.
AB  - Zinc and mercury are common contaminants of estuaries and coastal ecosystems
      where they may induce adverse effects on the biota. Carcinus maenas is a key
      species in several European estuaries, living in close association with the
      sediment where a considerable number of environmental contaminants, including
      zinc and mercury may accumulate. In the present study, the acute effects of zinc
      and mercury on C. maenas from the Minho River Estuary (NW Portugal) were
      investigated by using the activity of the enzymes cholinesterase (ChE), lactate
      dehydrogenase (LDH) and glutathione S-transferases (GST) as effects' criteria.
      Crabs were exposed for 96h to several concentrations of Zn(2+) (0, 1.84, 3.71,
      7.39 and 14.79mg/l) or Hg(2+) (0, 0.09, 0.19, 0.37 and 0.74mg/l). The choice of
      Zn(2+) test concentrations was based on the LC50 value (14.86mg/l) determined in
      a first part of the study, while the choice of Hg(2+) concentrations was based on
      values from the literature. At the end of the bioassays, eye, muscle and
      hepatopancreas tissues were isolated and used for ChE, LDH and GST
      determinations, respectively. Zinc significantly inhibited ChE activity (p<0.05,
      EC50=14.68mg/l), caused significant alterations of GST activity (p<0.05) and
      induced LDH activity (p<0.05) at the exposure of 14.79mg/l. Mercury significantly
      inhibited ChE activity (p<0.001, LOEC=0.09mg/l, EC50=0.235mg/l) and increased
      both GST (p<0.05, LOEC=0.774mg/l) and LDH activities (p<0.05, LOEC=0.119mg/l).
      These results suggest that both metals interfere with cholinergic
      neurotransmission in C. maenas by inhibiting ChE activity. In addition, they also
      interfere with GST activity and this may reduce the capacity of detoxification of
      some chemicals and/or to increase the probability of oxidative stress to occur.
      Furthermore, both metals increase LDH activity, suggesting an interference with
      energy production pathways. Therefore, the presence of zinc and mercury in
      estuaries at concentrations in the mg/l or mug/l range, respectively, may have a
      negative impact on C. maenas.

PMID- 16949640
TI  - Polybrominated diphenyl ethers in house dust in Singapore.
AB  - The use of polybrominated diphenyl ethers (PBDEs) as flame retardants in
      Singapore is not strictly regulated; therefore these compounds can be readily
      found in furniture, electronic devices, and building materials. This study was
      the first of its kind to be conducted in Singapore to measure concentrations of
      PBDEs in house dust. Samples were collected from 31 homes in various locations
      across the island-state of Singapore, and a total eight PBDEs congeners were
      measured. PBDEs were detected in all 31 dust samples and the number of BDE
      congener detected per home ranged between 3 and 8. The most abundant BDE
      congeners found were BDE 47, 99 and 209, with a median value of 20 ng g(-1) dust,
      24 ng g(-1) dust and 1000 ng g(-1) dust, respectively. BDE 209 contributed 88% to
      the median of all the congeners, and BDE 47 and 99 contributed 1.8% and 3.5%,
      respectively. Different congener profiles were observed between this and studies
      conducted elsewhere, which is consistent with the use of different commercial
      PBDE around the world. No significant correlations between PBDE dust levels and
      residential characteristics (number of TVs and computers, floor area or flooring
      material) were observed. The daily intake of PBDEs via the inhalation pathway was
      estimated. House dust may be regarded as the most important exposure route of
      PBDEs for children.

PMID- 16949641
TI  - Expression of Smac/DIABLO in B-cell non-Hodgkin and Hodgkin lymphomas.
AB  - Inhibitor of apoptosis proteins (IAPs) are upregulated in cancers and suppress
      cell death, in part, through their ability to directly inhibit caspases.
      Inhibitor of apoptosis proteins are differentially expressed in B-cell lymphomas.
      The functions of some IAPs are counteracted by the cell death inducer, second
      mitochondrial-derived activator of caspases/direct IAP binding protein with low
      pI (Smac/DIABLO). In this study, we investigated the expression levels of
      Smac/DIABLO in 14 lymphoma cell lines by Western blot analysis. We also assessed
      247 B-cell non-Hodgkin's lymphoma (NHL) and 40 Hodgkin's lymphoma (HL) tumors
      using immunohistochemical methods. Smac/DIABLO was expressed in most NHL and all
      HL cell lines. In NHL, Smac/DIABLO was expressed in 117 (47%) tumors and was
      differentially expressed in various NHL types. In most NHLs, from 29% to 68% of
      tumors were positive; however, Smac/DIABLO was not detected in small lymphocytic
      lymphoma/chronic lymphocytic leukemia and Burkitt lymphoma, and was rare in
      extranodal marginal zone B-cell lymphoma. In HL, Smac/DIABLO was positive in 25
      (63%) tumors. Unlike NHL, all types of HL were positive for Smac/DIABLO, although
      nodular sclerosis was least often positive. The differential expression of
      Smac/DIABLO in NHLs suggests that apoptotic mechanisms are differentially
      involved in their pathogenesis. These results may also have implications for
      using Smac/DIABLO or its agonists as therapeutic agents.

PMID- 16949643
TI  - A novel tumor marker, Niban, is expressed in subsets of thyroid tumors and
      Hashimoto's thyroiditis.
AB  - Niban is a recently identified molecular marker of renal carcinogenesis in the
      Tsc2 gene-mutant Eker rat. Niban expression is most dramatically increased in the
      early stage of renal carcinogenesis and might decline during malignant
      progression. Niban is also expressed in various histologic types of human renal
      cell carcinoma. Therefore, Niban might be a good marker for renal carcinogenesis
      in both animal models and humans. In the present study, we examined Niban
      expression in various thyroid lesions by immunohistochemical staining using
      polyclonal rabbit antihuman Niban antibody. Normal thyroid tissue never stained
      for Niban. Niban was most frequently expressed in tumors with oxyphilic
      cytoplasm, including oxyphilic variants of papillary carcinoma (4/4 = 100%),
      oxyphilic variants of follicular adenoma (7/7 = 100%), and oxyphilic variants of
      follicular carcinoma (5/5 = 100%). Eighty-one percent (44/54) of papillary
      carcinoma cases, including microcarcinomas, and follicular variants were also
      positively stained for Niban at variable intensities. Follicular carcinomas were
      less frequently and less intensely stained. In nonneoplastic lesions, cells were
      rarely positively stained. In Hashimoto's thyroiditis, scattered cells with
      oxyphilic cell metaplasia were weakly Niban-positive. Reverse transcriptase
      polymerase chain reaction and Western blot analysis of frozen tissue confirmed
      Niban expression at the molecular level in 4 cases of papillary carcinoma. Taken
      together, Niban expression is up-regulated in various types of thyroid tumors. We
      postulate that Niban expression may play an important role in the tumorigenic
      process of the thyroid in several scenarios. (1) Niban expression may be closely
      related to the carcinogenic process, especially from the early stage of papillary
      thyroid carcinoma. (2) Niban may be closely associated with altered mitochondrial
      functions in preneoplastic and neoplastic processes of the thyroid. (3) Niban may
      be a molecular marker of the oxyphilic phenotype under various conditions.
      Further functional studies of Niban will clarify the role of Niban in various
      thyroid lesions.

PMID- 16949642
TI  - Expression of bcl2 family proteins and active caspase 3 in classical Hodgkin's
      lymphomas.
AB  - The expression of various bcl2 family proteins has been reported in Hodgkin and
      Reed-Sternberg cells, but the proteins bad, bid, and bim have not been analyzed
      in classical Hodgkin's lymphomas (HLs). This study aimed to investigate the
      expression of the proteins bcl2, bcl-xl, mcl1, bax, bak, bad, bid, bim, and
      active caspase 3, and the TUNEL (terminal deoxynucleotidyl transferase-mediated
      in situ labeling) index to gain further insight into the apoptosis profile of
      classical HLs. A high expression of the proteins bcl2, bcl-xl, mcl1, bax, bak,
      bad, bid, and bim in HRS cells was found in 27 of 101 (27%), 95 of 101 (94%), 27
      of 97 (29%), 73 of 95 (77%), 37 of 102 (36%), 85 of 94 (90%), 19 of 109 (17%),
      and 43 of 91 (47%) cases, respectively. The high expression of bcl-xl, bax, and
      bad in HRS cells in most classical HLs indicates that these proteins may play
      predominant roles in the regulation of apoptosis in classical HLs. Active caspase
      3-positive and TUNEL-positive Reed-Sternberg cells were detected in 47 of 70
      (67%; range, 0%-12%) and 60 of 71 (85%; range, 0%-19%) cases, respectively.
      Significant positive correlations were found between bax/bcl2 (P = .002),
      bad/bcl2 (P = .020), bad/bcl-xl (P = .003), and bim/mcl1 (P = .036). Based on
      these findings, it could be hypothesized that the antiapoptotic proteins bcl2,
      bcl-xl, and mcl1 may counteract the expression of the proapoptotic proteins bax,
      bad, and bim, thereby contributing to the survival of Reed-Sternberg cells.

PMID- 16949644
TI  - A simple and rapid approach to the problem of tissue contamination and patient
      identity in histopathologic specimens.
AB  - Individual pathologists deal with thousands of diagnostic biopsy and excision
      specimens annually. At each stage, procedures are in place to limit the
      possibility of human error, which could result in specimen transposition or
      contamination. One specimen contaminating another is usually easily identified
      and rarely causes diagnostic difficulty; however, when it does, the consequences
      can be very serious. We discuss 5 cases in which concerns over specimen identity
      and tissue contamination arose and the methodology by which we resolved those
      concerns. Polymerase chain reaction analysis of each case was carried out using a
      panel of 12 polymorphic microsatellite markers, specific for chromosomes 13, 18,
      and 21. These markers are routinely used in the molecular genetics diagnostic
      laboratory for rapid trisomy screening. In each case, the question of error was
      satisfactorily resolved. Using this approach, we prevented the real possibility
      of patients undergoing second invasive procedures. We suggest that this or a
      similar methodology become a routine part of pathology practice.

PMID- 16949645
TI  - Type or extension of intestinal metaplasia and immature/atypical "indefinite-for
      dysplasia" lesions as predictors of gastric neoplasia.
AB  - At present, no information exists on the neoplastic potential of the immature
      hyperproliferative and atypical lesions of the gastric mucosa, which have been
      recently labeled "indefinite for dysplasia." In addition, uncertainties still
      exist concerning the risk contribution of intestinal metaplasia (IM) type and
      extension, as well as Helicobacter pylori infection. In this study, 471 dyspeptic
      patients showing IM 10% or higher (median, 40; 25th-75th percentile, 20-60) in
      antral, angulus, or corpus endoscopic biopsies were submitted to repeated
      examinations (median, 3; 2-5) over 52 (26-85) months of follow-up, during which
      44 neoplastic cases were recorded. IM extension, incomplete, sulfomucin-positive,
      or CAR5 antigen-positive IM; H pylori infection; and indefinite-for-dysplasia
      lesions (IDLs), as found at first examination, all showed significant neoplastic
      potential. However, only IDL, ongoing H pylori infection, and patient's age
      retained independent predictive power in a multivariate model. On the other hand,
      IM extension 20% or higher proved to be more sensitive as first screening
      parameter for identification of subjects with increased neoplastic risk. We
      suggest that patients with IM, when infected, should undergo H pylori eradication
      to reduce their cancer risk; only those bearing IDL or very extensive IM (which
      strongly correlates with IDL) should be followed up with endoscopies and
      biopsies.

PMID- 16949646
TI  - Occurrence of thymosin beta4 in human breast cancer cells and in other cell types
      of the tumor microenvironment.
AB  - Previous studies have shown that the G-actin sequestering polypeptide thymosin
      beta4 frequently is overexpressed in cancers and that such overexpression
      correlates to malignant progression. However, the localization of thymosin beta4
      in human cancers has not been determined. We now demonstrate that there is a
      considerable heterogeneity in the cellular distribution of thymosin beta4 in
      breast cancer. In most tumors examined, cancer cells showed low or intermediate
      reactivity for thymosin beta4, whereas leukocytes and macrophages showed intense
      reactivity. In addition, endothelial cells showed variable reactivity to thymosin
      beta4, whereas myofibroblasts were negative. There was no correlation between the
      intensity of tumor cell staining and histological grade, whereas there was a
      tendency toward a correlation between endothelial cell staining and grade. These
      results demonstrate that multiple cell types within the tumor microenvironment
      produce thymosin beta4 and that such expression varies from tumor to tumor. Such
      heterogeneity of expression should be taken into account when the role of
      thymosin beta4 in tumor biology is assessed.

PMID- 16949647
TI  - Nephron segment localization of polyoma virus large T antigen in renal
      allografts.
AB  - This study uses CD10 and epithelial membrane antigen (EMA) as respective proximal
      and distal tubular segment markers to localize polyoma virus replicative
      activity, as determined by large T antigen (TAg) expression, in allograft polyoma
      virus nephropathy (PVN). Sixteen biopsies and 2 nephrectomy specimens with PVN
      had serial 2-mum paraffin sections stained using monoclonal antibodies to polyoma
      virus TAg by immunoperoxidase with diaminobenzidine as chromogen. A second
      immunolabeling step used CD10 as a proximal nephron marker or EMA as a distal
      tubular marker, and alkaline phosphatase with fast red as chromogen. BK viral DNA
      was detected in blood in 16 of 18 tested. Fourteen of 16 had cortex and medulla,
      and 2 had cortex only in the biopsy sample. Fourteen (100%) of 14 had double
      positive EMA and TAg expression (EMA+TAg+) in medullary collecting ducts. T
      antigen was evident in loops of Henle in nephrectomies. Thirteen (81.3%) of 16
      had EMA+TAg+, and 10 (62.5%) of 16 had CD10+TAg+ cortical tubular segments.
      CD10+TAg+ cells were observed in the parietal epithelium of Bowman's capsule in 3
      biopsies (18.75%). T antigen was observed in 5.1% of CD10+ tubular profiles
      compared with 21% of EMA+ profiles in renal cortex (P < .0001). Polyoma virus TAg
      was observed in medullary collecting ducts, in distal and proximal cortical
      tubules, and in Bowman's capsule, in decreasing order of frequency. Loops of
      Henle also had TAg. This distribution suggests potential for an ascending route
      of infection of allograft tubules in PVN.

PMID- 16949648
TI  - Speleology and magnetobiostratigraphic chronology of the GD 2 locality of the
      Gondolin hominin-bearing paleocave deposits, North West Province, South Africa.
AB  - Speleological, paleomagnetic, mineral magnetic, and biochronological analyses
      have been undertaken at the Gondolin hominin-bearing paleocave, North West
      Province, South Africa. Two fossiliferous but stratigraphically separate
      sequences, GD2 and GD1/3, which were once part of a large cavern system, have
      been identified. Although some comparative paleomagnetic samples were taken from
      the GD 1, 3, and 4 localities that are currently under investigation, the
      research presented here focuses on the fossil-rich, in situ deposits at locality
      GD 2, excavated by E.S. Vrba in 1979. The GD 2 deposits are dominated by normal
      polarity calcified clastic deposits that are sandwiched between clastic-free
      flowstone speleothems. The lower flowstone has a sharp contact with the red
      siltstone deposits and is of reversed polarity. The capping flowstone shows a
      change from normal to reversed polarity, thereby preserving a polarity reversal.
      While the paleomagnetic work indicates that the GD 2 fossil material was
      deposited during a normal-polarity period, the shortness of the sequence made
      matching of the magnetostratigraphy to the geomagnetic polarity time scale (GPTS)
      impossible without the aid of biochronology. While lacking multiple time
      sensitive taxa, the recovery of specimens attributable to Stage III
      Metridiochoerus andrewsi is consistent with a deposition date between 1.9 and 1.5
      Ma. A comparison of the magnetostratigraphy with the GPTS therefore suggests that
      the fauna-bearing siltstone of GD 2 date to the Olduvai normal-polarity event,
      which occurred between 1.95 and 1.78 Ma, and that the reversal from normal to
      reversed polarity identified in the capping flowstone dates to 1.78 Ma. The main
      faunal layers therefore date to slightly older than 1.78 Ma. Deposits from the GD
      1 locality are dominated by reversed directions of magnetization, which show that
      this deposit is not of the same age as the faunal layers from the GD 2 locality.

PMID- 16949649
TI  - Cadmium and zinc accumulation in soybean: A threat to food safety?
AB  - A greenhouse study was conducted to quantify cadmium and zinc accumulated by
      soybean (Glycine max (L.) Merr.) when the metals were supplied separately and
      together. The highest dose of cadmium (100 mg/kg) reduced plant height and dry
      weight (down to 40% and 34% of control, respectively); the highest dose of zinc
      (2000 mg/kg) reduced plant height to 55% of control and dry weight to 70% of
      control. With both metals present, the plants were approximately the same size as
      those treated with cadmium only. The concentration of cadmium in the roots was
      unaffected by zinc. In other tissues, the effect of zinc on the accumulation of
      cadmium depended on the doses provided. At low doses, the addition of zinc
      reduced the concentration of cadmium in aboveground tissues to 40-50% of that
      found in plants exposed to cadmium only. However, when applied in high doses, the
      presence of zinc in cadmium-contaminated soils increased the uptake and
      accumulation of cadmium in aboveground tissues by up to 42%. In contrast, at high
      doses, the presence of cadmium in zinc-contaminated soil resulted in
      approximately 35% lower concentrations of zinc in all tissues. At a lower dose,
      cadmium had no effect on concentration of zinc in the plant tissues. The effects
      of high doses of one metal on the uptake of the other metal can be partially
      explained by the effects of one metal on the bioavailability of the other metal.
      In soils to which only one metal was added, bioavailable cadmium was 70-80% of
      the total cadmium, and bioavailable zinc was 50-70% of the total zinc. When both
      metals were added to the soil, 80-100% of the cadmium and 46-60% of the zinc were
      bioavailable. Concentrations of both metals were highest in root tissues (10-fold
      higher for cadmium, and up to 2-fold higher for zinc). Although relatively little
      cadmium was translocated to pods and seeds, the seeds of all plants (including
      those from control and zinc-treated plants) had concentrations of cadmium 3-4
      times above the limit of 0.2 mg/kg set by the Codex Alimentarius Commission. This
      was surprising given that cadmium in the soil was only 1 mg/kg well below the
      maximum allowable amount for agricultural soil. While it is possible that more
      cadmium was accumulated by plants in this study than that which might occur under
      agricultural field conditions, these results reinforce the need to monitor
      concentrations of toxic metals in food crops.

PMID- 16949650
TI  - The influence of contrasting suspended particulate matter transport regimes on
      the bias and precision of flux estimates.
AB  - A large database (507 station-years) of daily suspended particulate matter (SPM)
      concentration and discharge data from 36 stations on river basins ranging from
      600 km(2) to 600,000 km(2) in size (USA and Europe) was collected to assess the
      effects of SPM transport regime on bias and imprecision of flux estimates when
      using infrequent surveys and the discharge-weighted mean concentration method. By
      extracting individual SPM concentrations and corresponding discharge values from
      the database, sampling frequencies from 12 to 200 per year were simulated using
      Monte Carlo techniques. The resulting estimates of yearly SPM fluxes were
      compared to reference fluxes derived from the complete database. For each station
      and given frequency, bias was measured by the median of relative errors between
      estimated and reference fluxes, and imprecision by the difference between the
      upper and lower deciles of relative errors. Results show that the SPM transport
      regime of rivers affects the bias and imprecision of fluxes estimated by the
      discharge-weighted mean concentration method for given sampling frequencies (e.g.
      weekly, bimonthly, monthly). The percentage of annual SPM flux discharged in 2%
      of time (Ms(2)) is a robust indicator of SPM transport regime directly related to
      bias and imprecision. These errors are linked to the Ms(2) indicator for various
      sampling frequencies within a specific nomograph. For instance, based on a
      deviation of simulated flux estimates from reference fluxes lower than +/-20% and
      a bias lower than 1% or 2%, the required sampling intervals are less than 3 days
      for rivers with Ms(2) greater than 40% (basin size<10,000 km(2)), between 3 and 5
      days for rivers with Ms(2) between 30 and 40% (basin size between 10,000 and
      50,000 km(2)), between 5 and 12 days for Ms(2) from 20% to 30% (basin size
      between 50,000 and 200,000 km(2)), 12-20 days for Ms(2) in the 15-20% range
      (basin size between 200,000 and 500,000 km(2)).

PMID- 16949651
TI  - Differential calmodulin gene expression in the nuclei of the rat midbrain-brain
      stem region.
AB  - We investigated the expression patterns of the three calmodulin (CaM) genes,
      using in situ hybridization techniques, to detect gene-specific [(35)S]- and
      digoxigenin-labeled cRNA probes complementary to the multiple CaM mRNAs in the
      nuclei of the midbrain-brain stem region of the adult rat. The distinct CaM genes
      were widely expressed throughout this region with moderate intensities. In spite
      of the similar general pattern, significant differences in the distributions of
      the multiple CaM mRNA species were found in certain areas. In general, the CaM
      III mRNAs were most abundant, followed by the CaM I and CaM II mRNA populations.
      Most of the transcripts were found in the neuronal somata comprising the medullar
      nuclei, while much less label was detected in the neuropil. The CaM III mRNAs
      were more than 2.5 times more abundant than the CaM II mRNAs in the nucleus of
      the trapezoid body, and more than two times more abundant in the motor trigeminal
      nucleus, the principal sensory trigeminal nucleus and the olivary nucleus. The
      CaM III mRNAs were less dominant in the medial lemniscus, the inferior colliculus
      and the pontine reticular nucleus than those of the other CaM gene-specific
      transcripts. The CaM mRNA levels were low to moderate, without significant
      differences, in the mesencephalic trigeminal nucleus. The differential control of
      the expression of the CaM genes may contribute to the regulation of the multiple
      neuronal functions linked to this complex brain region and regulated by different
      CaM-dependent mechanisms via its target proteins.

PMID- 16949652
TI  - Medical diagnostic applications and sources.
AB  - The ways in which ultrasound is used in medical diagnosis are reviewed, with
      particular emphasis on the ultrasound source (probe) and implications for
      acoustic exposure. A brief discussion of the choice of optimum frequency for
      various target depths is followed by a description of the general features of
      diagnostic ultrasound probes, including endo-probes. The different modes of
      diagnostic scanning are then discussed in turn: A-mode, M-mode, B-mode, three
      dimensional (3D) and 4D scanning, continuous wave (CW) Doppler, pulse-wave
      spectral Doppler and Doppler imaging. Under the general heading of B-mode
      imaging, there are individual descriptions of the principles of chirps and binary
      codes, B-flow, tissue harmonic imaging and ultrasound contrast agent-specific
      techniques. Techniques for improving image quality within the constraints of real
      time operation are discussed, including write zoom, parallel beam forming,
      spatial compounding and multiple zone transmission focusing, along with methods
      for reducing slice thickness. At the end of each section there is a summarising
      comment on the basic features of the acoustic output and its consequences for
      patient safety.

PMID- 16949653
TI  - Quantification of risk from fetal exposure to diagnostic ultrasound.
AB  - Biomedical ultrasound may induce adverse effects in patients by either thermal or
      non-thermal means. Temperatures above normal can adversely affect biological
      systems, but effects also may be produced without significant heating. Thermally
      induced teratogenesis has been demonstrated in many animal species as well as in
      a few controlled studies in humans. Various maximum 'safe' temperature elevations
      have been proposed, although the suggested values range from 0.0 to 2.5 degrees
      C. Factors relevant to thermal effects are considered, including the nature of
      the acoustic field in situ, the state of perfusion of the embryo/fetus, and the
      variation of sensitivity to thermal insult with gestational stage of development.
      Non-thermal mechanisms of action considered include acoustic cavitation,
      radiation force, and acoustic streaming. While cavitation can be quite
      destructive, it is extremely unlikely in the absence of stabilized gas bodies,
      and although the remaining mechanisms may occur in utero, they have not been
      shown to induce adverse effects. For example, pulsed, diagnostic ultrasound can
      increase fetal activity during exposure, apparently due to stimulation of
      auditory perception by radiation forces on the fetal head or auditory structures.
      In contrast, pulsed ultrasound also produces vascular damage near developing bone
      in the late-gestation mouse, but by a unknown mechanism and at levels above
      current US FDA output limits. It is concluded that: (1) thermal rather than
      nonthermal mechanisms are more likely to induce adverse effects in utero, and (2)
      while the probability of an adverse thermal event is usually small, under some
      conditions it can be disturbingly high.

PMID- 16949654
TI  - Physical environment modulates the behavioral responses induced by chemical
      stimulation of dorsal periaqueductal gray in mice.
AB  - In order to investigate the relationship between behaviors elicited by chemical
      stimulation of the dorsal periaqueductal gray (dorsal PAG) and spontaneous
      defensive behaviors to a predator, the excitatory amino acid D,L-homocysteic acid
      (5 nmol in 0.1 micro l), was infused into the dorsal PAG and behavioral responses
      of mice were evaluated in two different situations, a rectangular novel chamber
      or the Mouse Defense Test Battery (MDTB) apparatus. During a 1-min period
      following drug infusion, more jumps were made in the chamber than in the MDTB
      runway but running time and distance traveled were significantly higher in the
      runway. Animals were subsequently tested using the standard MDTB procedure (anti
      predator avoidance, chase and defensive threat/attack). No drug effects on these
      measures were significant. In a further test in the MDTB apparatus, the pathway
      of the mouse during peak locomotion response was blocked 3 times by the predator
      stimulus (anesthetized rat) to determine if the mouse would avoid contact. Ninety
      percent of D,L-homocysteic treated animals made direct contact with the stimulus
      (rat), indicating that D,L-homocysteic-induced running is not guided by relevant
      (here, threat) stimuli. These results indicate that running as opposed to jumping
      is the primary response in mice injected with D,L-homocysteic into the dorsal PAG
      when the environment enables flight. However, the lack of responsivity to the
      predator during peak locomotion suggests that D,L-homocysteic-stimulation into
      the dorsal PAG does not induce normal antipredator flight.

PMID- 16949655
TI  - Tobacco smoking in relation to pain in a national general population survey.
AB  - BACKGROUND: We examined whether smoking status including heavy smoking (20 or
      more cigarettes per day) is related to the number of pain locations and intensity
      of pain. METHODS: A probability sample of the German national population aged 18
      to 79 including 7124 participants (response proportion: 61.4%) was used. All
      individuals underwent a health examination between 1997 and 1999. Ordinal
      logistic regression analyses were performed with number of pain locations and
      pain intensity as dependent variables which had been assessed by questionnaire.
      RESULTS: Former and current heavy smokers had higher odds for greater numbers of
      pain locations and for moderate and intense pain than never smokers after
      adjustment for analgesic medicament use and behavior-related risk factors. Female
      former heavy smokers had an adjusted odds ratio (OR) of 1.6 (95% confidence
      interval, CI, 1.2-2.2) and male former heavy smokers had an adjusted OR of 1.4
      (CI 1.1-1.8) for higher numbers of pain locations compared to never smoking women
      and men respectively (female current smokers: OR 1.4, CI 1.0-1.9; male current
      smokers: OR 1.3, CI 1.1-1.7). CONCLUSION: The findings suggest that former and
      current heavy smokers are more likely to report more pain locations and more
      intense pain than never smokers.

PMID- 16949656
TI  - Ten-year changes in sun protection behaviors and beliefs of young adults in 13
      European countries.
AB  - OBJECTIVE: Sun protection behaviors are important to the prevention of skin
      cancers, but little is known about changes over time in attitudes and behavior.
      METHODS: Cross-sectional surveys were carried out among university students in
      thirteen European countries in 1990 (n = 10,241) and 2000 (n = 10,161). Sun
      protection behavior and beliefs about the importance of sunscreen use for health
      were measured. RESULTS: There was little change in the proportion of men and
      women who sunbathed, but use of sun protection increased over the 10-year
      interval from 52% to 63% in men and 80% to 87% in women. There was wide variation
      in sun protection use and strength of health beliefs between countries. The
      association between strength of beliefs and behavior was more marked in 2000 than
      1990. Sun protection behavior was positively associated with the socioeconomic
      background of participants. CONCLUSION: The use of sunscreen increased among
      educated young Europeans from several countries over the 1990s, but important sex
      differences remain. Awareness of the risk to health of unprotected sunbathing is
      high, but there is scope of strengthening attitudes to sunscreen use.

PMID- 16949657
TI  - Genome-wide high-resolution mapping and functional analysis of DNA methylation in
      arabidopsis.
AB  - Cytosine methylation is important for transposon silencing and epigenetic
      regulation of endogenous genes, although the extent to which this DNA
      modification functions to regulate the genome is still unknown. Here we report
      the first comprehensive DNA methylation map of an entire genome, at 35 base pair
      resolution, using the flowering plant Arabidopsis thaliana as a model. We find
      that pericentromeric heterochromatin, repetitive sequences, and regions producing
      small interfering RNAs are heavily methylated. Unexpectedly, over one-third of
      expressed genes contain methylation within transcribed regions, whereas only
      approximately 5% of genes show methylation within promoter regions.
      Interestingly, genes methylated in transcribed regions are highly expressed and
      constitutively active, whereas promoter-methylated genes show a greater degree of
      tissue-specific expression. Whole-genome tiling-array transcriptional profiling
      of DNA methyltransferase null mutants identified hundreds of genes and intergenic
      noncoding RNAs with altered expression levels, many of which may be
      epigenetically controlled by DNA methylation.

PMID- 16949658
TI  - Effect of administration of prostaglandin F2alpha or presence of an estrous
      teaser bitch on characteristics of the canine ejaculate.
AB  - Semen was collected from eight dogs after SC administration of 0.1mg/kg PGF2alpha
      or 0.6 mL 0.9% NaCl solution 15 min prior to collection in the presence or
      absence of an estrous teaser bitch (switchback design; all dogs given all four
      treatments in random sequence). There were more spermatozoa (P=0.02) in
      ejaculates collected after administration of PGF2alpha in the presence of an
      estrous teaser bitch ((852+/-736)x10(6), mean+/-S.D.) than in ejaculates
      collected in saline-treated dogs in the absence of a teaser bitch ((371+/
      620)x10(6)). However, the number of spermatozoa in the ejaculate of dogs given
      PGF2alpha in the absence of a teaser bitch and in dogs given saline in the
      presence of a teaser bitch ((556+/-494 and 600+/-622)x10(6), respectively) were
      not significantly different from each other or from the other two groups. The
      percentage of morphologically normal spermatozoa did not vary by treatment
      (P=0.51). In conclusion, treatment with PGF2alpha and presence of a teaser bitch
      had an additive effect on the number of spermatozoa. This, coupled with
      relatively minor side-effects, suggests this is a useful technique to increase
      number of spermatozoa in a single canine ejaculate.

PMID- 16949659
TI  - Durability of resin-dentin bonds: effects of direct/indirect exposure and storage
      media.
AB  - OBJECTIVES: To evaluate the longevity of resin-dentin bonds of three adhesives
      using different storage media and specimen size. METHODS: Flat dentin surfaces
      from extracted human third molars were bonded with: a two-step etch-and-rinse
      self-priming adhesive (Single Bond), a two-step self-etching adhesive (Clearfil
      SE Bond), and a one-step self-etching adhesive (One-Up Bond F). Composite build
      ups were constructed. The bonded teeth were stored under three conditions: dry,
      distilled water, or mineral oil. Half of the specimens were stored as intact
      bonded teeth (Indirect Exposure/IE). The other half were first sectioned into
      beams and stored under same conditions (Direct Exposure/DE). After storage
      periods of 24h, 3 months or 1 year, the intact teeth (IE) were sectioned into
      beams and both subgroups (DE and IE) were tested for microtensile bond strengths.
      Results were analyzed with multiple ANOVA and Student-Newman-Keuls tests.
      Fractographic analysis was performed by SEM. RESULTS: After 24h, Single Bond and
      Clearfil SE Bond performed equally and were superior to One-Up Bond F. After 3
      months of DE to water storage, decreases in bond strengths were observed for
      Single Bond and One-Up Bond F, this decrease occurred for Clearfil SE Bond after
      12 months of water storage. Bonded specimens aged in dry did not alter bond
      strengths over time. Bond strength increased when Single Bond was stored in
      mineral oil after 3 and 12 months. Micromorphological alterations were evident
      after water storage. SIGNIFICANCE: Although dentin bond strength of all the
      adhesives fell over time in DE, SE Bond fells the least.

PMID- 16949660
TI  - Effect of short-term water storage on the elastic properties of some dental
      restorative materials--A resonant ultrasound spectroscopy study.
AB  - OBJECTIVES: This study was aimed to determine if short-term water storage would
      change elastic properties of dental composite materials. METHODS: Particulate
      filler composite resin and continuous unidirectional E-glass FRC materials were
      photopolymerized and additionally post-polymerized by heat for testing elastic
      properties with the Resonance Ultrasound Spectroscopy method as a function of
      time in water storage. The test specimens were stored in 37 degrees C water for
      up to 30 days. RESULTS: About 1% weight increase due to water sorption was
      observed in both materials with both polymerization methods. Water sorption did
      not change the resonance frequencies towards lower values, indicating no
      significant decrease in elastic properties in these materials. Because of high
      damping of the polymer composite materials leading to wide resonance peaks and
      low number of the recorded peaks, accurate determination of the elastic
      properties was not possible. SIGNIFICANCE: Results suggest that the most likely
      explanation for the previously observed decrease in bending stiffness of FRC
      materials is the decreased yield limit of the hydrated polymer matrix. It is
      important to recognize that water sorption has the effect on mechanical
      properties of dental composite materials by changing the yield limit of the
      matrix rather than by changing the elastic properties of the material.

PMID- 16949661
TI  - Restoring cervical lesions with flexible composites.
AB  - OBJECTIVES: Flexure at the tooth cervix has been suggested to dislodge cervical
      restorations more rapidly. The objective of this randomized controlled clinical
      trial was to test the hypothesis that a higher composite flexibility better
      withstands tooth flexure stress. METHODS: One hundred and forty-two non-carious
      cervical lesions were restored with composites with contrasting stiffness.
      Seventy-one patients randomly received two cervical restorations placed following
      two out of the three experimental groups: (1) the three-step etch-and-rinse
      adhesive Permaquick applied with the stiff micro-hybrid composite Amelogen Hybrid
      (PMQ/A-Hy, Ultradent), (2) Permaquick applied with the more flexible micro-filled
      composite Amelogen Microfill (PMQ/A-Mi, Ultradent), or (3) the 'golden standard'
      three-step etch-and-rinse adhesive Optibond FL applied with the micro-hybrid
      composite Prodigy (O-FL/Pro, Kerr). RESULTS: The recall rate at 7 years was 80%.
      No statistically significant difference was found for any of the parameters
      evaluated neither between both adhesives, nor between both composites (McNemar,
      p>0.05). Eleven percent of the O-FL/Pro restorations were clinically unacceptable
      due to loss of retention (5.5%) and severe marginal discoloration (5.5%). In the
      PMQ-group, 22% of the PMQ/A-Mi restorations (8% loss of retention, 5% severe
      enamel margin defects, 3% severe dentin margin defects, 6% severe marginal
      discoloration, 3% extreme sensitivity) and 19% of the PMQ/A-Hy restorations (13%
      loss of retention, 3% severe enamel margin defects, 3% severe marginal
      discoloration) needed repair or replacement. SIGNIFICANCE: The clinical
      performance of the three adhesive/composite combinations was good and reliable
      during the 7-year clinical trial. It was concluded that the composite stiffness
      does not affect the clinical longevity of cervical composite restorations.

PMID- 16949663
TI  - Isolation and characterization of chitin from bumblebee (Bombus terrestris).
AB  - Insect chitin possessing shell-like structure was prepared from the bumblebee
      corpses by a consequent treatment with 1M HCl and 1M NaOH. The bumblebee chitin
      was compared with crustacean (shrimp) chitin by using elemental analysis, Fourier
      transform infrared (FT-IR) and solid-state (13)C cross-polarization magic angle
      spinning nuclear magnetic resonance (CP/MAS)-NMR spectroscopy and confocal
      microscopy. Both chitins (bumblebee and shrimp) exhibited identical spectra,
      while the bumblebee chitin had a 5% lower degree of acetylation and was
      characterized by a fine membrane texture.

PMID- 16949662
TI  - Bioaccumulation of 14C-PCB 101 and 14C-PBDE 99 in the marine planktonic copepod
      Calanus finmarchicus under different food regimes.
AB  - Bioaccumulation factors (BAFs) were determined for (14)C-PCB 101 and (14)C-PBDE
      99 in the pelagic copepod Calanus finmarchicus after exposure to either
      contaminated water or after being fed contaminated phytoplankton (the
      dinoflagellate Prorocentrum minimum or the diatom Thalassiosira weissflogii).
      BAFs in algae range from 7.6 to 8.0 for PCB 101 and from 8.5 to 8.6 for PBDE 99.
      BAFs in copepods were significantly lower, 6.3-6.8 for PCB 101 and 7.6 for PBDE
      99. For each compound, the BAFs in copepods were independent of what algal
      species they had consumed, even though the bioaccumulation of both compounds were
      higher in P. minimum than in T. weissflogii. The ratios between BAF and the K(ow)
      for PCB 101 and PBDE 99 were similar within each of the three species, but varied
      between species. For copepods the ratios were 2-4, for T. weissfloggii 15-22 and
      for P. minimum 32-40. The data strongly suggest that the two compounds
      bioaccumulate in a similar manner and that there is no biomagnification in the
      transfer between phytoplankton and herbivorous copepods.

PMID- 16949665
TI  - Identification and partial characterization of a highly active and stable
      phospholipase D from Brassica juncea seeds.
AB  - Phospholipase D (PLD) activity has been identified in some new plant sources i.e.
      Brassica juncea (mustard) seeds, Zingibar officinale (ginger) rhizomes and
      Azadirachta indica (neem) leaves with the aim of identifying PLDs that possess
      high catalytic activity and stability. PLD from mustard seeds (PLD(ms)) exhibited
      the highest PLD specific activity, which was highly pH and temperature tolerant.
      PLD(ms) unlike many plant PLDs exhibited high thermal stability. The activity of
      PLD(ms) is optimum in the millimolar concentration of calcium ions and is
      independent of phosphatidylinositol-4,5-bisphosphate (PIP2). An active and stable
      enzyme like PLD(ms) may be utilized in the lipid industry.

PMID- 16949664
TI  - Molecular analysis and solution structure from small-angle X-ray scattering of
      the human natural killer inhibitory receptor IRp60 (CD300a).
AB  - Natural killer (NK) cells are lymphocytes of the innate immune system specialized
      in recognition and killing of certain virus-infected and tumor cells. To carry
      out this task, NK cells are equipped with a complex array of germ line encoded
      receptors. These receptors deliver either positive or negative signals, and a
      delicate balance between these signals governs the NK cell cytolytic activity
      against the target cell. IRp60 (CD300a) is a human NK inhibitory receptor with an
      immunoglobulin-like fold. In the present study the IRp60 protein was expressed in
      Escherichia coli as inclusion bodies and refolded by dilution. The refolded
      protein was purified to homogeneity, biochemical characterized and the solution
      structure was investigated using small-angle X-ray scattering (SAXS). The SAXS
      data revealed that IRp60 is monomeric in solution with a molecular shape
      characteristic of the immunoglobulin-like structures. A homology model of IRp60
      was built and validated experimentally against the SAXS data.

PMID- 16949666
TI  - The effect of anisotropic architecture on cell and tissue infiltration into
      tissue engineering scaffolds.
AB  - A common phenomenon in tissue engineering is rapid tissue formation on the outer
      edge of the scaffold which restricts cell penetration and nutrient exchange to
      the scaffold centre, resulting in a necrotic core. To address this problem, we
      generated scaffolds with both random and anisotropic open porous architectures to
      enhance cell and subsequent tissue infiltration throughout the scaffold for
      applications in bone and cartilage engineering. Hydroxyapatite (HA) and poly(D,L
      lactic acid) (P(DL)LA) scaffolds with random open porosity were manufactured,
      using modified slip-casting and by supercritical fluid processing respectively,
      and subsequently characterised. An array of porous aligned channels (400 microm)
      was incorporated into both scaffold types and cell (human osteoblast sarcoma, for
      HA scaffolds; ovine meniscal fibrochondrocytes, for P(DL)LA scaffolds) and tissue
      infiltration into these modified scaffolds was assessed in vitro (cell
      penetration) and in vivo (tissue infiltration; HA scaffolds only). Scaffolds were
      shown to have an extensive random, open porous structure with an average porosity
      of 85%. Enhanced cell and tissue penetration was observed both in vitro and in
      vivo demonstrating that scaffold design alone can influence cell and tissue
      infiltration into the centre of tissue engineering scaffolds.

PMID- 16949667
TI  - Use of hydrodynamic forces to engineer cartilaginous tissues resembling the non
      uniform structure and function of meniscus.
AB  - The aim of this study was to demonstrate that differences in the local
      composition of bi-zonal fibrocartilaginous tissues result in different local
      biomechanical properties in compression and tension. Bovine articular
      chondrocytes were loaded into hyaluronan-based meshes (HYAFF-11) and cultured for
      4 weeks in mixed flask, a rotary Cell Culture System (RCCS), or statically.
      Resulting tissues were assessed histologically, immunohistochemically, by
      scanning electron microscopy and mechanically in different regions. Local
      mechanical analyses in compression and tension were performed by indentation-type
      scanning force microscopy and by tensile tests on punched out concentric rings,
      respectively. Tissues cultured in mixed flask or RCCS displayed an outer region
      positively stained for versican and type I collagen, and an inner region
      positively stained for glycosaminoglycans and types I and II collagen. The outer
      fibrocartilaginous capsule included bundles (up to 2 microm diameter) of collagen
      fibers and was stiffer in tension (up to 3.6-fold higher elastic modulus),
      whereas the inner region was stiffer in compression (up to 3.8-fold higher
      elastic modulus). Instead, molecule distribution and mechanical properties were
      similar in the outer and inner regions of statically grown tissues. In
      conclusion, exposure of articular chondrocyte-based constructs to hydrodynamic
      flow generated tissues with locally different composition and mechanical
      properties, resembling some aspects of the complex structure and function of the
      outer and inner zones of native meniscus.

PMID- 16949668
TI  - Delivery of dexamethasone, ascorbate, and growth factor (TGF beta-3) in thermo
      reversible hydrogel constructs embedded with rabbit chondrocytes.
AB  - The aim of this study was to assess the efficacy of poly(N-isopropylacrylamide-co
      acrylic acid) (p(NiPAAm-co-AAc)) as an injectable drug delivery vehicle and a
      cell therapeutic agent in the form of a supporting matrix for the chondrogenic
      differentiation of rabbit chondrocytes. The p(NiPAAm-co-AAc) hydrogel itself
      without specific differentiation-inducing drugs was used as a control in order to
      determine the effects of these materials on chondrogenic differentiation. The
      level of cartilage associated extracellular matrix (ECM) proteins was examined by
      immunohistochemical staining for collagen type II as well as Safranin-O and
      Alcian blue (GAG) staining. These results highlight the potential of a thermo
      reversible hydrogel mixed with chondrocytes and differentiation materials as an
      injectable delivery vehicle for use in neocartilage formation.

PMID- 16949669
TI  - Prospects for prostate cancer imaging and therapy using high-affinity TRPM8
      activators.
AB  - One of the best-studied temperature-gated channels is transient receptor
      potential melastatin 8 (TRPM8), which is activated by cold and cooling agents,
      such as menthol. Besides inducing a cooling sensation in sensory neurons, TRPM8
      channel activation also plays a major role in physiopathology. Indeed, TRPMP8
      expression increases in early stages of prostate cancer and its involvement in
      prostate cell apoptosis has recently been demonstrated. Thus, as TRPM8 is a tumor
      marker with significant potential use in diagnosis, as well as a target for
      cancer therapy, there is a need for new TRPM8-specific ligands. In this study, we
      investigated the action of "WS" compounds on TRPM8 channels. We compared the
      affinity of these molecules to that of menthol and icilin. This enabled us to
      identify new TRPM8 agonists. The menthol analog with the highest affinity, WS-12,
      had an EC(50) value about 2000 times lower than that of menthol and is,
      therefore, the highest-affinity TRPM8 ligand known to date. Finally,
      incorporating a fluorine atom in the WS-12 retained 75% of the activity of the
      parent compound. The high affinity of this new TRPM8 ligand and the possibility
      of incorporating a radiohalogen could thus be useful for diagnosis, monitoring
      and, perhaps, even therapy of prostate cancer.

PMID- 16949670
TI  - Fibrates upregulate TRB3 in lymphocytes independent of PPAR alpha by augmenting
      CCAAT/enhancer-binding protein beta (C/EBP beta) expression.
AB  - Fibrates, which function by binding and activating peroxisome proliferator
      activated receptor alpha (PPARalpha), have been used successfully to treat
      hyperlipidemia and atherosclerosis. Increasing evidence suggests that in addition
      to their lipid lowering activities these medications also function as
      immunosuppressive agents. Tribbles is a Drosophila protein that slows cell cycle
      progression, and its mammalian homolog, TRB3 interferes with insulin-induced
      activation of AKT. In these studies we demonstrate that fibrates upregulate TRB3
      expression in mitogen-activated lymphocytes. Interestingly, in lymphocytes
      fibrates augment TRB3 expression in both PPARalpha wildtype and knockout mice,
      suggesting that upregulation of this protein occurs in a PPARalpha-independent
      manner. Fibrates activate a proximal TRB3 promoter construct and mutation or
      partial deletion of a potential PPAR response element does not alter the ability
      of fibrates to drive TRB3 expression. Subsequent studies reveal that fibrates
      upregulate C/EBPbeta and CHOP in lymphocytes and mutation of potential C/EBPbeta
      and CHOP consensus sequences abrogates the ability of fibrates to upregulate TRB3
      promoter activity. Accordingly, fibrates enhance the recruitment of C/EBPbeta and
      CHOP to the proximal TRB3 promoter. Finally, TRB3 expression in lymphocytes
      induces G2 cell cycle delay and cellular depletion. These studies outline a novel
      PPARalpha-independent mechanism of action of fibrates and document for the first
      time the expression of TRB3 in activated lymphocytes.

PMID- 16949671
TI  - Soman poisoning induces delayed astrogliotic scar and angiogenesis in damaged
      mouse brain areas.
AB  - Gliotic scar formation and angiogenesis are two biological events involved in the
      tissue reparative process generally occurring in the brain after mechanically
      induced injury, ischemia or cerebral tumor development. For the first time, in
      this study, neo-vascularization and glial scar formation were investigated in the
      brain of soman-poisoned mice over a 3-month period after nerve agent exposure
      (1.2 LD50 of soman). Using anti-claudin-5 and anti-vascular endothelial growth
      factor (VEGF) immunostaining techniques on brain sections, blood vessels were
      quantified and VEGF expression was verified to appraise the level of neo
      angiogenesis induced in damaged brain areas. Furthermore, glial scar formation
      and neuropathology were estimated over time in the same injured brain regions by
      anti-glial fibrillary acidic protein (GFAP) immunohistochemistry and hemalun
      phloxin (H&P) dye staining, respectively. VEGF over-expression was noticed on
      post-soman day 3 in lesioned areas such as the hippocampal CA1 field and
      amygdala. This was followed by an increase in the quantity of mature blood
      vessels, 3 months after soman poisoning, in the same brain areas. On the other
      hand, massive astroglial cell activation was demonstrated on post-soman day 8.
      Reactive astroglial cells were located only in damaged cerebral regions where H&P
      stained eosinophilic neurons were found. For longer experimental times,
      astroglial response slowly decreased overtime but remained detectable on post
      soman day 90 in some discrete brain regions (i.e. CA1 field and amygdala)
      evidencing the formation of a glial scar. In this study, we discuss the key role
      of VEGF in the angiogenic process and in the glial or neuronal response induced
      by soman poisoning.

PMID- 16949672
TI  - Cavitary Legionella pneumonia in a patient with immunodeficiency due to Hyper-IgE
      syndrome.
AB  - We report about a 35-year-old man with a cavitary legionella pneumonia who had a
      history of chronic eczematoid lesions since infancy, recurrent skin and lung
      infections and a very high total IgE level. We carried out further investigations
      and made a diagnosis of a primary immunodeficiency classified in the Hyper-IgE
      syndromes. Cavitation of legionella pneumonia may become fairly common in
      immunocompromised patients, while is found rarely among immunocompetent hosts.

PMID- 16949673
TI  - Enigmatic GABAergic networks in adult neurogenic zones.
AB  - The discovery and description of complex GABAergic networks in adult neurogenic
      zones suggest the intriguing possibility of information transfer from neuronal
      activity to immature cells. New questions also emerge regarding the mode of
      GABAergic signaling and the temporal pattern of receptor activation. Non-synaptic
      (paracrine) signaling communicates information on population size to control the
      proliferation and migration of progenitor cells in the subventricular zone. How
      this signaling relates to olfactory bulb network activity, however, remains
      largely unknown. This review argues that paracrine signaling precedes and then co
      exists with synaptic GABAergic signaling, which provides the timing and
      instruction for cells to properly differentiate and synaptically integrate into
      an existing network. The evidence examined in this review indicates that the
      commonly cited mechanism of GABA's action (i.e., depolarization leading to
      voltage-gated calcium channel activation and calcium entry) needs to be re
      examined in the context of the unique cellular properties and organization of the
      adult neurogenic regions.

PMID- 16949674
TI  - Quantification of MPTP-induced dopaminergic neurodegeneration in the mouse
      substantia nigra by laser capture microdissection.
AB  - The neurotoxin MPTP is widely used to cause damage to the dopaminergic system in
      rodents and non-human primates to model various aspects of Parkinson's disease.
      In mice, depletion of striatal dopamine is the commonly used endpoint to assess
      neuronal damage. However, it has proved technically challenging to quantify
      dopaminergic cell bodies as an index of neuronal integrity. To meet this
      challenge, we applied laser pressure catapult microdissection (LCM) of the
      substantia nigra in combination with quantitative Western blot to provide an
      index of dopamine neurodegeneration in mice treated with MPTP. Seven days
      following initiation of MPTP treatment, striatal dopamine depletion was maximal
      and there was histological evidence of neuronal degeneration in the substantia
      nigra. To index the integrity of dopamine cell bodies, tyrosine hydroxylase (TH)
      and beta-actin were quantified by Western blot in LCM extracts. In untreated
      mice, TH was detected in LCM extracts of substantia nigra but was undetectable in
      equivalently sized extracts of cortex from the same animals. In MPTP-treated
      mice, there was a significant 70% reduction in TH relative to beta-actin in LCM
      extracts as compared to vehicle-injected controls. This reduction corresponded to
      decreases in striatal dopamine and loss of immunocytochemically detected TH but
      not beta-actin in the substantia nigra (SN). Thus, this method provides a
      quantitative means to measure dopamine neuron toxicity in the substantia nigra
      and, as such has potential application in evaluating regimens that may be
      neuroprotective or neurorestorative for dopaminergic neurons.

PMID- 16949675
TI  - Measurement of blast wave by a miniature fiber optic pressure transducer in the
      rat brain.
AB  - Exposure to blast wave that is generated during an explosion may result in brain
      damage and related neurological impairments. The aim of this study was to
      investigate pressure changes induced by exposure to blast inside the rat brain.
      For intracranial pressure measurement we used a miniature optic fiber sensor
      (o.d. 550 microm) with a computer recording system. The sensor was placed in the
      third cerebral ventricle of anesthetized rats exposed to 40 kPa blast wave in a
      pneumatic-pressure driven shock tube. Short pressure waves lasting several ms
      were detected inside the brain with the magnitude that might result in nervous
      tissue damage.

PMID- 16949676
TI  - Effects of surface EMG rectification on power and coherence analyses: an EEG and
      MEG study.
AB  - Coherence between electromyography (EMG) and electroencephalography (EEG) or
      magnetoencephalography (MEG) is frequently examined to gain insights on
      neuromuscular binding. Commonly, EMG signals are rectified before coherence is
      computed. However, the appropriateness of EMG rectification in computing EMG
      EEG/MEG coherence has never been validated. Since rectification is a non-linear
      operation and alters the EMG power spectrum, such a validation is important to
      ensure the accuracy of coherence calculation. In this study we experimentally
      investigated the effects of EMG rectification on EMG power spectra and its
      coherence with EEG/MEG signals. Subjects performed sustained isometric index
      finger abduction at approximately 5-10% maximal voluntary force (in both EEG-EMG
      and MEG-EMG experiments) and index finger tapping at approximately 2-4Hz (in EEG
      EMG experiment only). Bipolar surface EMG data from the first dorsal interosseus
      (FDI) and EEG/MEG signals from the contralateral primary sensorimotor area (C3)
      were recorded simultaneously. Power spectra and coherence with the EEG/MEG were
      calculated before and after EMG rectification. The results show that
      rectification shifts EMG power to lower frequencies, possibly enhancing peaks of
      motor unit firing. Coherences with the EEG/MEG signals were not significantly
      changed by EMG rectification, indicating EMG rectification is overall an
      appropriate procedure in power and coherence analyses.

PMID- 16949677
TI  - Bactericidal activity of macrophages against Streptococcus uberis is different in
      mammary gland secretions of lactating and drying off cows.
AB  - The aim of this study was to compare the ability of milk macrophages and
      macrophages from the mammary gland secretions during the mid-dry period for their
      interaction with the mastitis-causing Streptococcus uberis. We also aimed to
      determine if S. uberis induced the release of the cytokine tumour necrosis alpha
      (TNF-alpha) and the bactericidal moiety nitric oxide (NO) from milk macrophages
      of lactating cows and macrophages from the mammary gland secretions at the mid
      dry period. Macrophages were isolated from the mammary gland secretions of cows
      during the mid-lactation or mid-dry period, and compared with blood monocytes for
      their interaction with the important mastitis-causing pathogen S. uberis. When
      infected in vitro with S. uberis, milk macrophages from lactating cows with S.
      uberis released modest amounts of the cytokine tumour necrosis factor alpha (TNF
      alpha) (139 pg/ml) and the bactericidal moiety nitric oxide (NO) (3-4 microM of
      nitrite). Blood monocytes from lactating cows released significantly higher
      amounts of TNF-alpha (345 +/- 143 pg/ml) and NO (7 +/- 2 microM of nitrite) after
      interaction with S. uberis, compared to milk macrophages (P < 0.01 for both TNF
      alpha and NO). Stimulation of blood monocytes with the cytokine interferon-gamma
      (IFN-gamma) enhanced significantly the release of NO and TNF-alpha, but IFN-gamma
      did not significantly enhance the production of NO and TNF-alpha by milk
      macrophages from lactating cows. Milk macrophages from all lactating cows failed
      to kill S. uberis efficiently, and this lack of killing was unaffected by prior
      treatment with gamma interferon (IFN-gamma) (P > 0.05). Rather, S. uberis
      multiplied significantly inside infected milk macrophages from lactating cows,
      with a two-fold increase in bacterial numbers at 2 h post-infection. Milk
      macrophages from lactating cows were able however, to kill a significant
      proportion (50-60%, P < 0.01) of phagocytosed Staphylococcus aureus. Blood
      monocytes from all cows were found to exert significant bactericidal activity
      against S. uberis. There were no significant differences in the bactericidal
      activity of milk macrophages obtained from lactating cows with low somatic cell
      counts (SCC; < 10(5) ml(-1)) compared with those with a mildly elevated SCC (>
      10(5) ml(-1)) (P > 0.05). In contrast, mammary gland secretion macrophages
      isolated from the same cows in the mid-dry period killed a significant proportion
      of phagocytosed S. uberis (50-65% of ingested S. uberis killed, P < 0.01)
      although cytokine production in response to in vitro bacterial infection was low.
      We conclude that the bactericidal activity of mammary gland secretion macrophages
      against a virulent strain of S. uberis is low during the lactation period. In
      addition, our data indicate that S. uberis is not a strong inducer of NO and TNF
      alpha in macrophages from the milk or mammary gland secretions of cows during the
      drying off period. Finally, IFN-gamma does not activate milk macrophages or
      macrophages from cows during the lactating period or mammary gland secretions
      during the drying off period.

PMID- 16949678
TI  - Age-associated changes within CD4+ T cells.
AB  - As individuals age their ability to respond and clear pathogens declines, leading
      to a greater incidence and severity of infectious diseases. Additionally, the
      efficacy of vaccines is frequently decreased in elderly persons. Increased
      susceptibility to infections and reduced protection after vaccination reflect the
      impact of age-related changes on the immune system. The immune system undergoes a
      wide range of changes with increasing age. The aim of this review is to summarize
      cellular and molecular aspects of aging CD4(+) T cells. CD4(+) T cells play an
      essential role in mediating both humoral and cellular immune responses.
      Therefore, age-associated dysfunctions within CD4(+) T cells have a strong
      clinical impact. Improving our understanding of the aged CD4(+) T cells, in
      particular but also of the aged immune system in general, is crucial for
      developing effective prevention and treatment programs which will facilitate
      healthy aging and improve the quality of life of the elderly population.

PMID- 16949679
TI  - Codon optimized expression of HPV 16 E6 renders target cells susceptible to E6
      specific CTL recognition.
AB  - The early proteins E6 and E7 of the cancer-related human papillomavirus type 16
      (HPV 16) are constitutively expressed in cancer cells thus are targets for immune
      therapeutic approaches. Whereas previous studies have mainly focussed on the
      immunogenicity of E7 protein little is known about E6. In order to evaluate E6
      specific DNA immunization strategies in a preclinical mouse model C57BL/6 mice
      were injected with plasmid pTHampE6 and analyzed for E6-specific CTL induction.
      CTL specific for the H2-K(b)-restricted E6-derived epitope E6 48-57, were readily
      detectable among splenocytes of immunized animals, however, these CTL showed a
      differential recognition pattern on various E6-expressing target cells. Using a
      newly generated E6-specific monoclonal antibody we found that most cell lines
      expressing E6 encoded by the natural gene showed undetectable protein amounts and
      were ignored by E6-specific CTL. However, transfection of a codon optimized
      version of the E6 gene (E6opt) strongly enhanced protein expression levels within
      these cells turning them into susceptible target cells. Surprisingly, we found
      that E6-positive TC-1 cells, although recognized by E6-specific CTL, were totally
      devoid of any detectable E6 protein. Inhibition of proteasomal function by
      lactacystin treatment diminished E6-specific CTL recognition of TC-1 cells and
      RMA/E6opt transfectants accompanied by intracellular accumulation of E6 protein
      as observed in RMA/E6opt transfectants, but not in TC-1 cells. These data suggest
      that in TC-1 cells rapid degradation processes might prevent stable expression of
      E6 protein yet generate precursor peptides in amounts sufficient for MHC class I
      restricted antigen presentation. Thus, the results presented in this paper show
      that: (i) use of optimized codons in transfection experiments can improve
      susceptibility of target cells to E6-specific CTL recognition and (ii) lack of
      detectable protein within a cell does not necessarily indicate the absence of
      epitope presentation. Both findings are of potential relevance for the design of
      tumor vaccines.

PMID- 16949680
TI  - Ultrasound diagnosis of an internal carotid artery pseudoaneurysm in a young
      child.
AB  - Pseudoaneurysm of the carotid artery is a rare complication of deep neck space
      infection. It carries a high mortality rate even when treated appropriately. We
      report a case of a pseudoaneurysm of the internal carotid artery in a 2-year-old
      child who had a neck infection without an associated abscess. The diagnosis was
      not obvious on MRI but was confirmed by ultrasonography. This was successfully
      managed by angiographic embolization, followed by antibiotic and anticoagulant
      treatment. The combination of MRI and ultrasonography, without the use of
      invasive or radiation techniques, was sufficient for the diagnosis of
      pseudoaneurysm of the internal carotid artery.

PMID- 16949681
TI  - Parameters of inhibition of HIV-1 infection by small anionic microbicides.
AB  - Sulfonated porphyrins and phthalocyanines have been shown to have anti-HIV
      activity and are under consideration as microbicides. Both categories of
      compounds are small negatively charged molecules and both were previously shown
      to inhibit cell fusion induced by the HIV Env protein and to block binding of
      gp120 to the CD4 receptor. In the present study we show that these compounds
      inhibit transmission of cell-associated HIV, inactivate a broad range of HIV-1
      primary isolates and are active against DS polyanion-resistant virus. The
      compounds tested are active over a range of pH values, and possess no detectable
      activity against normal bacterial flora. These results support the conclusion
      that anionic tetrapyrroles are promising candidates as microbicides for HIV
      prevention.

PMID- 16949682
TI  - Effects of fluoxetine on behavioral deficits evoked by chronic social stress in
      rats.
AB  - Recently, we described an advanced model of chronic social stress in male rats
      based on the resident intruder paradigm. In this model, rats subjected to daily
      social stress for 5 weeks showed behavioral changes resembling anhedonia and
      motivational deficits in humans. In the present study, male Wistar rats were
      subjected to 5 weeks of daily social defeat by an aggressive conspecific and
      concomitant treatment with the antidepressant drug fluoxetine (10 mg/kg) after
      the first week of stress. Compared with controls, rats exposed to chronic stress
      had significantly reduced locomotor and exploratory activity (rearing and
      sniffing) and diminished preference for sucrose solution. These effects were
      paralleled by decreased body weight gain, increased adrenal weights and decreased
      plasma levels of testosterone measured post mortem. The stress-induced effects on
      locomotor activity and rearing behavior were counteracted by fluoxetine
      treatment.

PMID- 16949683
TI  - Effect of waterborne exposure to 4-tert-octylphenol and 17beta-estradiol on
      smoltification and downstream migration in Atlantic salmon, Salmo salar.
AB  - Groups of Atlantic salmon parr (November, Exp. 1) or pre-smolts (March, Exp. 2)
      were exposed to estradiol-17beta (E2 conc.: nominal 500 ngl(-1)/actual 8-16 ngl(
      1)) and two doses of tert-octylphenol (OP: nominal 25 microgl(-1)/actual 4.5-6.5
      microgl(-1) and OP: nominal 100 microgl(-1)/actual 10-30 microgl(-1)) for 26 days
      in fresh water, and the effects on physiological and behavioural aspects of parr
      smolt transformation were investigated. Vitellogenesis was induced by all
      treatments, as indicated by elevated levels of plasma vitellogenin (Vtg) and
      hepatosomatic index. Elevated Vtg levels were still found in OP-100 and E2
      treated fish 4-5 months after cessation of treatment, indicating a slow clearance
      of Vtg from circulation. Smolting was compromised by E2 and OP-100 treatment as
      judged by reduced gill Na(+), K(+)-ATPase activity and impaired ability to
      regulate plasma osmolality and muscle water content in 24-h sea water (SW)
      challenge tests during the period of smolting. Downstream migratory behaviour was
      monitored from late April to July (Exp. 2) by implanting passive integrated
      transponder tags into subgroups of treated and control smolts and placing them in
      a stream raceway. Irrespective of treatment, nocturnal downstream movement was
      initiated in all groups on April 23, switching to diurnal movement in late May.
      Average swimming speed was estimated to be higher than current speed, indicating
      active migration. E2 and OP-100 fish migrated at lower frequency than control
      fish, suggesting a reduced migratory drive. The data suggests that waterborne
      exposure of salmon to xenoestrogens reduce both physiological and behavioural
      components of smoltification, even when exposure occurs several months prior to
      smolting.

PMID- 16949684
TI  - Signaling mechanisms of vasoactive intestinal peptide in inflammatory conditions.
AB  - The vasoactive intestinal peptide (VIP) is a neuropeptide belonging to the
      secretin/glucagon family of peptides, which exerts a wide spectrum of
      immunological functions controlling the homeostasis of immune system through
      different receptors expressed in various immunocompetent cells. In the last
      decade, VIP has emerged as a potent anti-inflammatory factor, which exerts its
      function by regulating the production of both anti- and pro-inflammatory
      mediators. In this sense, VIP has been proposed as a promising candidate,
      alternative to other existing treatments, for treating acute and chronic
      inflammatory and autoimmune diseases, such as septic shock, rheumatoid arthritis,
      multiple sclerosis and Crohn's disease. The present work reviews the involvement
      of the specific receptors and or different transduction pathways and
      transcription factors in the anti-inflammatory action of VIP, and their
      implication on its therapeutic effect on inflammatory/autoimmune disorders.

PMID- 16949685
TI  - Drosophila distal-less negatively regulates dDREF by inhibiting its DNA binding
      activity.
AB  - The Drosophila DNA replication-related element binding factor (dDREF) is required
      for expression of many proliferation-related genes carrying the DRE sequence, 5'
      TATCGATA. Over-expression of dDREF in the eye imaginal disc induces ectopic DNA
      synthesis, apoptosis and inhibition of photoreceptor cell specification, and
      results in rough eye phenotype in adults. In the present study, half dose
      reduction of the Distal-less (Dll) gene enhanced the dDREF-induced rough eye
      phenotype, suggesting that Dll negatively regulates dDREF activity in eye
      imaginal disc cells. Biochemical analyses revealed the N-terminal (30aa to 124aa)
      and C-terminal (190aa to 327aa) regions of Dll to interact with the DNA binding
      domain (16aa to 125aa) of dDREF, although it is not clear yet whether the
      interaction is direct or indirect. Electrophoretic mobility shift assays showed
      that Dll thereby inhibits DNA binding. The repression of this dDREF-function by a
      homeodomain protein like Dll may contribute to the differentiation-coupled
      repression of cell proliferation during development.

PMID- 16949686
TI  - Molecular cloning and functional expression of the Penaeus monodon 5-HT receptor.
AB  - Serotonin (5-HT) mediates a number of diverse physiological functions in
      crustaceans by interacting with various 5-HT receptor subtypes. A putative 5-HT
      receptor cloned from the ovary of the black tiger prawn (Penaeus monodon)
      consisted of 2291 nucleotides, encoding a putative 5-HT(1Pem) receptor protein of
      591 amino acids. Transient expression of 5-HT(1Pem) in HEK293 cells demonstrated
      a saturable [3H]-5-HT binding with a Kd of 10.43+/-1.13 nM and Bmax of 1.53+/
      0.06 pmol/mg. The putative 5-HT(1Pem) receptor is expressed in all tissues
      examined and is constitutively expressed in the ovary during ovarian maturation
      and spent phase. Polyclonal antibodies against the third intracellular loop (i3
      loop) of the 5-HT receptor showed that the 5-HT(1Pem) receptor protein was
      expressed in the trabeculae of ovarian stages 1 and 2 but on the cortical rod and
      surrounding the oocyte membrane of stages 3 and 4, suggesting that receptor
      localization plays a critical role in regulating ovarian maturation and spawning
      in penaeus shrimp.

PMID- 16949687
TI  - Upregulation of human angiotensinogen (AGT) gene transcription by interferon
      gamma: involvement of the STAT1-binding motif in the AGT promoter.
AB  - Mechanisms to maintain blood pressure in the face of infection are critical to
      survival. The angiotensinogen (AGT) gene locus is an important component of this
      response. Thus the AGT gene, expressed predominantly by liver cells, is known to
      be a positive acute phase reactant. We have previously demonstrated activation of
      the AGT promoter in hepatocytes through the IL6/STAT3 signaling mechanism. We
      have now investigated whether IFN-gamma, a cytokine also induced in response to
      diverse infections, can regulate AGT gene expression, and have elucidated the
      molecular mechanism involved. IFN gamma treatment up-regulated AGT mRNA level and
      promoter activity in Hep3B hepatocytes. Sequential deletion of the promoter from
      the 5' side suggested the major IFN gamma responsive DNA element to be between 
      303 and -103. This region contained a candidate STAT1-binding site between -271
      and -279. EMSA and chromatin immuno-precipitation (ChIP) assays confirmed that
      IFN-gamma treatment induced the binding of STAT1 to this element. Reporter
      constructs containing this AGT promoter derived element in a multimerized context
      but not a mutant version were responsive to IFN gamma. Moreover mutating this
      STAT1 element in the context of the wild-type AGT holo promoter reduced
      responsiveness to IFN gamma. In contrast to the clear synergism between
      dexamethasone and IL 6 in the upregulation of the AGT promoter (through
      interaction between GR and STAT3), the combination of IFN gamma with IL 6 or with
      dexamethasone did not further increase AGT promoter activity suggesting that the
      IFN gamma/STAT1 pathway represents a separate signaling mechanism. These data
      highlight the redundancy in cytokine-mediated host response pathways aimed at the
      maintenance of blood pressure during infection.

PMID- 16949688
TI  - X-linked adrenoleukodystrophy: clinical, biochemical and pathogenetic aspects.
AB  - X-linked adrenoleukodystrophy (X-ALD) is a clinically heterogeneous disorder
      ranging from the severe childhood cerebral form to asymptomatic persons. The
      overall incidence is 1:16,800 including hemizygotes as well as heterozygotes. The
      principal molecular defect is due to inborn mutations in the ABCD1 gene encoding
      the adrenoleukodystrophy protein (ALDP), a transporter in the peroxisome
      membrane. ALDP is involved in the transport of substrates from the cytoplasm into
      the peroxisomal lumen. ALDP defects lead to characteristic accumulation of
      saturated very long-chain fatty acids, the diagnostic disease marker. The
      pathogenesis is unclear. Different molecular mechanisms seem to induce
      inflammatory demyelination, neurodegeneration and adrenocortical insufficiency
      involving the primary ABCD1 defect, environmental factors and modifier genes.
      Important information has been derived from the X-ALD mouse models; species
      differences however complicate the interpretation of results. So far, bone marrow
      transplantation is the only effective long-term treatment for childhood cerebral
      X-ALD, however, only when performed at an early-stage of disease. Urgently needed
      novel therapeutic strategies are under consideration ranging from dietary
      approaches to gene therapy.

PMID- 16949689
TI  - Statin use and prognosis in patients with advanced heart failure.
AB  - Statin therapy is associated with improved outcome in patients with advanced
      systolic heart failure with coronary artery disease (adjusted Hazard Ratio 0.33,
      95% confidence interval 0.13-0.83) but not in patients without coronary artery
      disease (adjusted Hazard Ratio 0.93, 95% confidence interval 0.26-3.4).

PMID- 16949690
TI  - Cost-effectiveness of coronary artery disease screening in asymptomatic patients
      with type 2 diabetes and other atherogenic risk factors in Japan: factors
      influencing on international application of evidence-based guidelines.
AB  - BACKGROUND: Screening for coronary artery disease (CAD) in asymptomatic diabetic
      patients with atherogenic risk factors is recommended by the American College of
      Cardiology/American Diabetes Association. It is not clear whether these
      guidelines apply to the Japanese population with a different epidemiology of CAD.
      This study evaluates the applicability of the U.S. guidelines to Japan, taking
      account of cost-effectiveness. DESIGN: A cost-effectiveness analysis using a
      Markov model was performed to measure the clinical benefit and cost of CAD
      screening in asymptomatic patients with diabetes and additional atherogenic risk
      factors. We evaluated cohorts of patients stratified by age, gender, and
      atherogenic risks. The incremental cost-effectiveness of not screening, exercise
      electrocardiography, exercise echocardiography, and exercise single-photon
      emission-tomography (SPECT) was calculated. The data used were obtained from the
      literature. Outcomes are expressed as US dollars per quality-adjusted life year
      (QALY). RESULTS: Compared with not screening, the incremental cost-effectiveness
      ratio (ICER) of exercise electrocardiography was $31,400/QALY for 60-year-old
      asymptomatic diabetic men, and 46,600 for 65-year-old women with hypertension and
      smoking. The ICER of exercise echocardiography was $31,500/QALY and of SPECT was
      $326,000/QALY, compared with the next dominant strategy. Sensitivity analyses
      found that these results varied according to age, gender, the combination of
      additional atherogenic risk factors, and the frequency of screening. CONCLUSION:
      From a societal perspective the U.S. guidelines on screening for CAD in high risk
      diabetic patients are applicable to the Japanese population. However, the
      population subjected to screening should be carefully selected to obtain greatest
      benefit from screening.

PMID- 16949691
TI  - Emergency percutaneous angioplasty of unprotected left main coronary artery in
      the setting of myocardial infarction: experience of a low volume center without
      surgical back up.

PMID- 16949692
TI  - Money and mental wellbeing: a longitudinal study of medium-sized lottery wins.
AB  - One of the famous questions in social science is whether money makes people
      happy. We offer new evidence by using longitudinal data on a random sample of
      Britons who receive medium-sized lottery wins of between 1000 pounds and 120,000
      pounds (that is, up to approximately US$ 200,000). When compared to two control
      groups -- one with no wins and the other with small wins -- these individuals go
      on eventually to exhibit significantly better psychological health. Two years
      after a lottery win, the average measured improvement in mental wellbeing is 1.4
      GHQ points.

PMID- 16949693
TI  - A laboratory hot tub model for disinfectant efficacy evaluation.
AB  - This paper describes a novel laboratory hot tub (LHT) apparatus and associated
      standard operating procedure (SOP) designed to reproduce the key biological,
      chemical, and engineering parameters associated with recreational and therapeutic
      hot tubs. Efficacy, as measured quantitatively by log reduction values, was
      determined against both biofilm and planktonic bacteria. When the LHT was run
      according to the SOP, with no antimicrobial treatment, a consistent level of
      bacterial contamination occurred. The means of log10 viable cell densities (+/-
      the repeatability standard deviation of log densities) were 7.2 (+/-0.31) for the
      bulk water (density in units of cfu ml-1), 5.3 (+/-0.56) for the coupons (density
      in units of cfu cm-2), and 6.6 (+/-0.50) for the filters (density in units of cfu
      cm-2). When control and chlorine treated LHTs were run in parallel, the log
      reduction increased significantly with chlorine concentration for samples of
      planktonic bacteria in the bulk water (p=0.016), biofilm bacteria on the coupons
      (p=0.09) and biofilm bacteria on the filter (p=0.005), indicating that the method
      was sensitive to chlorine concentration. The method also displayed sensitivity by
      differentiating between chlorine and bromine treatments; in every case, chlorine
      produced a greater log reduction than did the same concentration of bromine. The
      model and SOP were shown to be rugged with respect to slight changes in fluid
      mixing intensity, water chemistry (saturation index), inoculum size, and organic
      loading. The LHT and associated SOP provide a reliable second tier in a three
      tiered testing process, in which the first tier is a suspension test and the
      final tier is a field test.

PMID- 16949694
TI  - Evaluating the relationship between erectile dysfunction and dose received by the
      penile bulb: using data from a randomised controlled trial of conformal
      radiotherapy in prostate cancer (MRC RT01, ISRCTN47772397).
AB  - AIM: To evaluate the relationship between erectile function and the radiation
      dose to the penile bulb and other proximal penile structures in men receiving
      conformal radiotherapy (CFRT) for prostate cancer (PCa). METHODS: The Medical
      Research Council (MRC) RT01 trial randomised 843 men who had localised PCa to
      receive either 64 or 74 Gy after 3 - 6 months neoadjuvant hormonal treatment.
      Fifty-one men were selected who were potent prior to hormonal treatment, having
      completed both pre-hormone and 2-year post-CFRT Quality of Life assessments, and
      on whom dose volume data were available for analysis. The men were divided into
      three groups according to 2-year follow-up: potent, reduced potency, and
      impotent. The bulb of the penis together with the crura, were outlined on
      restored treatment plans. Dose - volume histograms were generated and compared
      between the three groups. An ordered logistic regression model was used to
      calculate the odds ratio of a range of dose - volume parameters to the penile
      bulb and effect on erectile dysfunction. The dose to the penile bulb was
      correlated to the dose received by the crura. RESULTS: Of the 51 patients, 12
      remained potent, 22 had reduced potency, and 17 were impotent at 2 years. No
      differences were seen in mean dose to the penile bulb by allocated treatment (t
      test = 1.61, p = 0.11). The mean doses to the penile bulb received by the potent,
      reduced potency, and impotent groups were 45.5 Gy (SD 17.1), 48 Gy (SD 16.1), and
      59.2 Gy (SD 13.8), respectively. There was a strong correlation between the mean
      dose received by the penile bulb and dose to the crura (r = 0.82, p < 0.0001).
      83.3% of impotent patients received a D90 > or = 50 Gy to the penile bulb
      compared with 29.4% of patients who maintained potency at 2 years (p = 0.006).
      CONCLUSION: There is evidence from this study to suggest a dose volume effect on
      the penile bulb and erectile dysfunction. A D90 > or = 50 Gy is associated with a
      significant risk of erectile dysfunction and this should form a basis for
      selecting dose constraints in future dose escalation studies.

PMID- 16949695
TI  - Respiratory correlated segment reconstruction algorithm towards four-dimensional
      radiation therapy using carbon ion beams.
AB  - PURPOSE: To enhance the precision of treatment planning for tumors which move
      under respiration, we developed a respiratory-correlated segment reconstruction
      method (RS) based on the Feldkamp--Davis--Kress algorithm (FDK) which provides
      high temporal resolution and a high signal-to-noise ratio. We compared full-scan
      (FS-FDK) and RS-FDK with regard to dose distribution in heavy ion treatment
      planning. MATERIALS AND METHODS: Data acquisition for RS-FDK is done using a
      respiratory sensing system in cine scan mode with a 256-multi-detector row CT
      (256-MDCT). To evaluate the accuracy of irradiation of moving tumors, dose
      distributions with each algorithm were compared in heavy ion treatment planning
      using beam parameters obtained with FS-FDK. RESULTS: Images obtained using RS-FDK
      did not show motion artifacts and visualized the edges of the liver and pulmonary
      vessels more clearly than those with FS-FDK. The iso-dose distributions for FS
      FDK covered the target volume; in contrast, RS-FDK with the beam parameter of FS
      FDK image provided an insufficient dose to the target and a considerable dose to
      normal tissues around it. CONCLUSIONS: The information provided by RS-FDK
      improves accuracy in the prescription of dose-to-target volume. Further, RS-FDK
      allows greater precision in the delivery of radiotherapy, including 4D radiation
      therapy.

PMID- 16949696
TI  - Optimisation of culture conditions with respect to biotin requirement for the
      production of recombinant avidin in Pichia pastoris.
AB  - Due to its very high affinity to biotin, avidin is one of the most widely
      exploited proteins in modern biotechnological and biomedical applications. Since
      biotin is an essential vitamin for the growth of many microorganisms, we examined
      the effect of biotin deficiency on growth for a recombinant Pichia pastoris
      strain expressing and secreting a recombinant glycosylated avidin. The results
      showed that biotin deficiency lowers growth rate and biomass yield for P.
      pastoris. Substitution of biotin in the medium by the two structurally unrelated
      compounds, aspartic acid and oleic acid, which do not bind to recombinant avidin
      was analyzed quantitatively. These two compounds had a growth promoting effect in
      biotin-deficient medium, but did not replace biotin completely. Indeed, in
      chemostat culture, wash-out occurred after about six liquid residence times and
      recombinant avidin productivity was lowered. However, addition of low amounts of
      biotin (20 microg L(-1) of biotin for a cell density of 8 g L(-1)) resulted in
      stable chemostat cultures on methanol with the production of recombinant biotin
      free avidin. The specific avidin production rate was 22 microg g(-1) h(-1) at a
      dilution rate of 0.06 h(-1).

PMID- 16949698
TI  - Differential roles of C4 and betaC1 in mediating suppression of post
      transcriptional gene silencing: evidence for transactivation by the C2 of Bhendi
      yellow vein mosaic virus, a monopartite begomovirus.
AB  - Bhendi yellow vein mosaic disease (BYVMD) is caused by the association of a DNA
      beta satellite with a begomovirus component. The begomovirus component has two
      promoters, one in the virion sense (V-sense) and the other in the complementary
      sense (C-sense) in the intergenic region (IR). To study the promoter activities
      of V-sense and C-sense promoters, mGFP gene fusion was made downstream to the
      promoters. Transient and stable expressions in N. benthamiana leaves showed
      significant GFP expression under C-sense promoter whereas the expression under
      the V-sense promoter was very weak in the absence of the transactivator C2.
      Untransformed N. benthamiana plants were agroinfiltrated with binary vector
      constructs containing V-sense-GFP alone or along with C1, C2, C4, V1, V2 or
      betaC1 (in both sense and antisense orientations) to understand the roles of
      these gene products in transactivation and/or suppression of post-transcriptional
      gene silencing (PTGS). The results showed strong suppression of gene silencing
      activities for C4 and betaC1 but a weak activity for C2. The suppression
      activities were also confirmed using gfp-silenced GFP16c/GFPi plants by
      agroinfiltration and agroinoculation. The expression of C4 and betaC1 as
      transgenes produced abnormal phenotypic growth compared to the other viral genes
      mentioned above, further supporting their suppressor function.

PMID- 16949697
TI  - Electrochemical sensing DNA damage with nano-titanium dioxide and repair with a
      medicinal herb species resveratrol.
AB  - We have developed a simple electrochemical method to detect DNA damage caused by
      the photovoltaic effect of nano-TiO(2). Meanwhile, we have found that
      resveratrol, a Chinese Traditional Medicinal Herb species, can have a repairing
      effect to the oxidized DNA, which can also be detected with the proposed
      technique in this paper.

PMID- 16949699
TI  - Structural requirements for assembly and homotypic interactions of the hepatitis
      C virus core protein.
AB  - The hepatitis C virus (HCV) core protein is involved in the assembly of
      nucleocapsid particles, as well as regulation of cellular and viral gene
      expression. To investigate the biological properties of the viral core protein
      and viral RNA assembly, two recombinant core proteins, the mature core protein
      (named C179) and a C-terminal truncated protein (named C124), were expressed and
      purified. To confirm their ability to generate viral particles, the production of
      nucleocapsid-like particles was monitored using transmission electron microscopy
      (EM). The EM analysis revealed that exposure of these proteins to the 5'
      untranslated region (5' UTR) of the viral RNA resulted in generation of spherical
      particles of 30-140nm in diameter. Interestingly, a cross-linking analysis
      revealed that C124 required an RNA component for homotypic interactions. In
      contrast, C179 successfully assembled in the absence of nucleic acids.
      Additionally, RNA-mediated conversion of the C124 structure into a more stable
      state was maintained even after RNase treatment. Therefore, our results indicate
      that the basic N-terminal domain of the viral core protein utilizes RNA
      components to induce conformational changes or efficient homotypic interactions,
      while the C-terminal domain may contain key peptide sequences for initiating
      spontaneous multimerization at the early stages of viral assembly.

PMID- 16949700
TI  - Diffuse alveolar damage after a single dose of topotecan in a patient with
      pulmonary fibrosis and small cell lung cancer.
AB  - Drug-induced pulmonary toxicities of anticancer agents have been well described,
      but the pathophysiology of agents typically used in advanced disease has not been
      well studied. Symptoms of pulmonary drug toxicity in advanced lung cancer
      patients may frequently be attributed to disease progression, pulmonary embolism,
      or infection. In patients with pre-existing interstitial pulmonary fibrosis even
      less is known. This report describes an unfortunate patient with pre-existing
      pulmonary fibrosis and progressive extensive stage small cell lung cancer. After
      receiving a single intravenous dose of topotecan, the patient developed sub-acute
      respiratory failure, and died 15 days later with pathology findings of
      organizing, reparative phase, diffuse alveolar damage. To our knowledge this is
      the first pathology confirmation of diffuse alveolar damage in a patient
      developing dyspnea following topotecan therapy. The frequency with which
      camptothecin-related dyspnea is associated with diffuse alveolar damage might be
      underestimated and is of special concern in patients with limited pulmonary
      reserve.

PMID- 16949701
TI  - Interleukin-1beta gene polymorphisms associated with risk of lung cancer in
      Japanese.

PMID- 16949702
TI  - Synthesis of oxysterols and nitrogenous sterols with antileishmanial and
      trypanocidal activities.
AB  - Two sterol families have been synthesized: the first one is nitrogenous sterols
      containing amino, N-hydroxyimino or cyano group and the second one is oxysterols
      such as ketosterol and hydroxysterols. These compounds were then evaluated in
      vitro against Leishmania donovani promastigotes and Trypanosoma brucei brucei
      trypomastigotes. The most active compounds against L. donovani promastigotes were
      7beta-aminomethylcholesterol and 7alpha,beta-aminocholesterol (IC50 in a range
      from 1 to 3 microM, pentamidine: 2.8 microM). These compounds were active on
      intramacrophage amastigotes with IC50 of 1.3 microM. Such an activity justifies
      further in vivo antileishmanial evaluation. Against T. b. brucei, (24R,S)-24
      hydroxy-24-methylcholesterol (MEC, 12.5 microM) was the most active compound from
      these series.

PMID- 16949703
TI  - [Cerebrospinal fluid in the pleura].

PMID- 16949704
TI  - [Cerebral venous thrombosis and ulcerative colitis].
AB  - INTRODUCTION: Thromboembolic events are serious complications in patients with
      inflammatory bowel disease. EXEGESIS: An 18-year-old patient, with a one year
      history of ulcerative colitis, presented with cerebral venous thrombosis during
      the decreasing period of corticotherapy after an active phase of the disease.
      Under treatment, the neurological disorder rapidly improved. No inherited
      thrombophilia was found. CONCLUSION: The role of acquired and inherited risks
      factors is discussed.

PMID- 16949705
TI  - [Skin discoloration].

PMID- 16949706
TI  - [Eczematous dermatitis from heparin].

PMID- 16949707
TI  - [Necrotic myocarditis in acute eosinophilic lymphoblastic leukaemia].
AB  - INTRODUCTION: Hypereosinophilia can cause severe cardiac complications. The
      association between an acute lymphoblastic leukemia and hypereosinophilia was
      rare. We report a case of a 29-year-old man who presented a heart failure
      secondary to necrotic myocarditis related to an acute eosinophilic lymphoblastic
      leukaemia. EXEGESIS: The patient developed a heart failure and secondary a cardio
      embolic stroke, due to a large mobile left ventricle thrombosis. His peripheral
      blood showed a total white count of 28,500 leucocytes/mm3 with 18,800
      eosinophils/mm3. The myelogram cytology showed precursor B-cell acute
      lymphoblastic leukaemia with hypereosinophilia. CONCLUSION: The possibility of
      the rapid emergence of cardiac lesions in hypereosinophilic syndromes warrants
      very close physician vigilance. An Echocardiography and MRI performed at the
      early stage and in the follow-up allow to detect and to manage these cardiac
      disorders.

PMID- 16949708
TI  - Surveillance of influenza immunisation uptake in people aged under 65 years with
      chronic disease.
AB  - Historically, it has been difficult to obtain population based data on the uptake
      of influenza immunisation in people aged under 65 years who are at risk of
      serious illness or death from influenza and its complications. Data obtained
      electronically from 96% of all practices in Wales demonstrated that uptake in
      this group is low, with only a quarter of eligible patients immunised. Uptake
      varies considerably between patient groups and between geographical areas. This
      suggests an opportunity for significant health gain from targeted interventions
      to improve uptake.

PMID- 16949709
TI  - Efficacy of particle-based DNA delivery for vaccination of sheep against FMDV.
AB  - As an alternative strategy to classical inactivated viral vaccine against FMDV,
      naked DNA vaccine is attractive because of safety, flexibility and low cost.
      However DNA vaccination is usually poorly efficient in target species. Indeed we
      found that naked DNA plasmids encoding for P1-2A3C3D and GM-CSF proteins did not
      induce any detectable immunity against FMDV in sheep. Interestingly, we
      demonstrate herein that formulations of DNA on poly(D,L-lactide-co-glycolide)
      (PLG) or in lipofectin triggered divergent types of immune responses: PLG
      stimulated a T cell response and could elicit significant neutralising antibody
      titers, whereas lipofectin generated even higher antibody titers but no
      significant T cell response. The DNA/PLG regimen used in five sheep protected
      against clinical symptoms and viraemia and prevented the carrier state in four of
      them. Thus formulated DNA can be remarkably efficient against FMDV in a ruminant
      species that is usually refractory to DNA vaccination.

PMID- 16949711
TI  - Effect of drying on the desorption of diuron and terbuthylazine from natural
      soils.
AB  - This work was initiated to study the effects of climate induced soil water status
      variations which can reach extreme values under natural conditions on the
      sorption process of hydrophobic organic compounds. Based on the classical slurry
      batch methodology an approach is developed that allows the fast and careful
      complete drying of soil suspensions (microwave technique). Classical adsorption
      experiments were followed by three desorption steps with and without drying
      cycles. Drying and re-wetting enhanced the sorption-desorption hysteresis and
      Freundlich adsorption coefficients increased from 5.9 to 16 and 5.2 to 21 over
      three drying cycles for diuron and terbuthylazine respectively. Assuming the
      validity of a dual stage adsorption process, model evaluation suggests that
      drying is as a shrinking-like process leading to conformational changes of the
      dominant sorbent (soil organic matter) which restrict the intra-micro-particle
      diffusion. Rewetting only leads to a partial recovery of the diffusional pore
      space.

PMID- 16949710
TI  - Long-term immunogenicity after single and booster dose of a live attenuated
      hepatitis A vaccine: results from 8-year follow-up.
AB  - Live, attenuated hepatitis A vaccines are used widely in China but there is
      uncertainty regarding the persistence of vaccine-induced anti-HAV antibodies
      after single dose and booster dose administrated at month 12. A large scale
      clinical trial to evaluate the live, attenuated hepatitis A vaccine was conducted
      in Hebei province between 1996 and 1999. Five years after the trials, children in
      single dose and booster dose groups were bled and followed. Seventy two percent
      (61/85) of children who received a single trial dose had detectable anti-HAV
      antibodies for 96 months (GMC at 96 months: 89.0 mIU/mL). In the booster group
      98% (48/49) children remained anti-HAV positive with GMC of 262.8 mIU/mL at month
      96. The reinjection with live attenuated HAV vaccine can elicit a booster effect.
      Results from single dose group seems not to support the need for booster doses of
      live attenuated hepatitis A vaccine in immunocompetent individuals regarding the
      persisting anti-HAV and anamnestic response of a single dose vaccine. Continued
      monitoring of anti-HAV antibodies is needed for a rational hepatitis A
      immunization strategy in China.

PMID- 16949712
TI  - Persistent organic pollutants in human breast milk from Asian countries.
AB  - In this paper, we concisely reviewed the contamination of persistent organic
      pollutants (POPs) such as polychlorinated dibenzo-p-dioxins (PCDDs),
      dibenzofurans (PCDFs), biphenyls (PCBs), dichlorodiphenyltrichloroethane and its
      metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), chlordane compounds
      (CHLs), hexachlorobenzene (HCB) in human breast milk collected from Asian
      countries such as Japan, China, Philippines, Vietnam, Cambodia, India, Malaysia,
      and Indonesia during 1999-2003. Dioxins, PCBs, CHLs in Japanese, and DDTs in
      Vietnamese, Chinese, Cambodian, Malaysian, and HCHs in Chinese, Indian, and HCB
      in Chinese breast milk were predominant. In India, levels of dioxins and related
      compounds (DRCs) in the mothers living around the open dumping site were notably
      higher than those from the reference site and other Asian developing countries,
      indicating that significant pollution sources of DRCs are present in the dumping
      site of India and the residents there have been exposed to relatively higher
      levels of these contaminants possibly via bovine milk.

PMID- 16949713
TI  - Creating meaning in fibromyalgia syndrome.
AB  - Gaining a diagnosis is considered to legitimate a person's illness, to both the
      self and the wider social world, while also giving hope that treatments, and
      possibly a cure, will be found. A further function of diagnosis from the
      patient's perspective is to give meaning to the illness experience, which is
      often uncertain and confusing. To do so, a diagnosis must itself have meaning.
      This paper explores the creation of meaning in a medically unexplained disorder,
      fibromyalgia syndrome (FMS). Semi-structured interviews, in which the diagnostic
      process was explored, were conducted with 17 people diagnosed with FMS in the
      United Kingdom, selected from a hospital database (16 women, 1 man). Documentary
      analysis was also undertaken on information available from support groups and
      health professionals. Although initially an acceptable diagnosis to sufferers,
      FMS was viewed as a mysterious label, which provided no meaning at the time of
      diagnosis. The sought information was accessed in an attempt to resolve its
      meaninglessness, but this proved problematic due to the ambiguous definition of
      FMS within the medical and support group literature, the invisible nature of the
      illness, and the lack of an environment where these uncertainties could be openly
      discussed. Informants varied in the degree of longer-term acceptance of a
      diagnosis of FMS, in relation to the concordance they achieved between the
      diagnosis and their experience of illness.

PMID- 16949714
TI  - Quantifier comprehension in corticobasal degeneration.
AB  - In this study, we investigated patients with focal neurodegenerative diseases to
      examine a formal linguistic distinction between classes of generalized
      quantifiers, like "some X" and "less than half of X." Our model of quantifier
      comprehension proposes that number knowledge is required to understand both first
      order and higher-order quantifiers. The present results demonstrate that
      corticobasal degeneration (CBD) patients, who have number knowledge impairments
      but little evidence for a deficit understanding other aspects of language, are
      impaired in their comprehension of quantifiers relative to healthy seniors,
      Alzheimer's disease (AD) and frontotemporal dementia (FTD) patients
      [F(3,77)=4.98; p<.005]. Moreover, our model attempts to honor a distinction in
      complexity between classes of quantifiers such that working memory is required to
      comprehend higher-order quantifiers. Our results support this distinction by
      demonstrating that FTD and AD patients, who have working memory limitations, have
      greater difficulty understanding higher-order quantifiers relative to first-order
      quantifiers [F(1,77)=124.29; p<.001]. An important implication of these findings
      is that the meaning of generalized quantifiers appears to involve two dissociable
      components, number knowledge and working memory, which are supported by distinct
      brain regions.

PMID- 16949715
TI  - A dose-response study following in utero and lactational exposure to di-(2
      ethylhexyl)-phthalate (DEHP): non-monotonic dose-response and low dose effects on
      rat brain aromatase activity.
AB  - Di-(2-ethylhexyl)-phthalate (DEHP) is a commonly used plasticizer which can act
      as an endocrine disruptor. It has been suggested that in addition to its
      antiandrogenic effects, DEHP may interfere with estrogen metabolism through
      suppression of aromatase enzyme activity. This enzyme catalyzes the conversion of
      testosterone to estradiol and plays a critical role in brain sexual
      differentiation. We investigated the effects of two wide ranges of DEHP doses on
      brain aromatase activity of male and female rat offspring. Wistar rat dams were
      treated daily with DEHP and peanut oil (control) by gavage from gestation day 6
      to lactation day 21 at doses of 0.015, 0.045, 0.135, 0.405 and
      1.215mgDEHP/kgbodyweight(bw)/day (low doses) and at 5, 15, 45, 135 and
      405mgDEHP/kgbw/day (high doses). Aromatase activity was determined in
      hypothalamic/preoptic area (HPOA) brain sections from male and female pups on
      postnatal days (PNDs) 1 and 22. In males on PND 1, aromatase activity was
      inhibited at low doses and increased at high doses resulting in a non-monotonic
      dose-response profile which resembled a J-shaped curve. Inhibition was
      statistically significant at 0.135 and 0.405mgDEHP/kg/day, while increased
      activity was observed at 15, 45 and 405mg/kg/day. In contrast to findings on PND
      1, aromatase activity at weaning (PND 22) was more affected in females than in
      males. An increase in aromatase activity was observed at only one dose in males
      (0.405mg/kg/day) while an increase in activity was observed at all doses in the
      females except for 0.045 and 5mgDEHP/kg/day. Overall, these results indicate that
      males and females respond differently to DEHP not only in regard to the age at
      which effects are manifested, but also in the shape of the dose-response curve.
      To our knowledge, this is the first study to report biological effects of DEHP at
      doses that overlap with the estimated exposure of the general human population.

PMID- 16949716
TI  - Silymarin causes caspases activation and apoptosis in K562 leukemia cells through
      inactivation of Akt pathway.
AB  - Cancer is one of the largest causes of death in both men and women. Akt,
      overexpressed in a number of human malignancies including leukemia, is an
      important target in cancer prevention and/or therapy. Silymarin, a flavonoid
      antioxidant, has high human acceptance being used clinically for the treatment of
      liver diseases. In this study, Akt activity was inhibited by silymarin without
      changes in total Akt level associated with a prominent caspases-9 and -3
      activation as well as PARP cleavage, accompanied by a strong apoptotic death and
      growth inhibition of K562 cells. These findings suggest that silymarin could
      serve as a candidate for anti-leukemia drug.

PMID- 16949717
TI  - The effect of hydrogen peroxide concentration on metal ion release from dental
      amalgam.
AB  - OBJECTIVES: The aim of this study was to investigate the effect of hydrogen
      peroxide (HP) concentration on metal ion release from dental amalgam. METHODS:
      Dental amalgam discs (n=25) were prepared by packing amalgam into cylindrical
      plastic moulds (10 mm diameter and 2 mm height). The discs were divided into five
      equal groups and each group was immersed in 20 ml of either 0%, 1%, 3%, 10% or
      30% HP solution for 24 h at 37 degrees C. Samples were taken for metal ion
      release determination (Hg, Ag, Sn and Cu) using inductively coupled plasma mass
      spectrometry (ICP-MS). The surface roughness of each disc was measured before and
      after bleaching. RESULTS: The differences in concentration of metal ions released
      after treatment with 0% (control) and each of 1%, 3%, 10% and 30% HP were
      statistically significant (p<0.05). Metal ion release for the elements (Hg, Ag,
      Sn and Cu) increased with exposure to increasing concentrations of HP. Surface
      roughness measurements of the samples before and after treatments with HP
      solutions were not significantly different (p>0.05). CONCLUSIONS: Exposure to HP
      bleaching agent was associated with increased metal ion released from dental
      amalgams compared to treatment with a control solution. Ion release was in
      proportion to the peroxide concentration tested, with the highest concentration
      associated with the greatest metal ion release for all elements investigated.

PMID- 16949718
TI  - Human adipose tissue binds and metabolizes the endocannabinoids anandamide and 2
      arachidonoylglycerol.
AB  - Endocannabinoids are a group of biologically active endogenous lipids that have
      recently emerged as important mediators in energy balance control. The two best
      studied endocannabinoids, anandamide (N-arachidonoylethanolamine, AEA) and 2
      arachidonoylglycerol (2-AG) are the endogenous ligands of the central and
      peripheral cannabinoid receptors. Furthermore, AEA binds to the transient
      receptor potential vanilloid type-1 (TRPV1), a capsaicin-sensitive, non-selective
      cation channel. The synthesis of these endocannabinoids is catalyzed by the N
      acylphosphatidylethanolamine-selective phospholipase D (NAPE-PLD) and the sn-1
      selective diacylglycerol lipase (DAGL), whereas their degradation is accomplished
      by the fatty acid amide hydrolase (FAAH) and the monoglyceride lipase (MGL),
      respectively. We investigated the presence of a functional endocannabinoid system
      in human adipose tissue from seven healthy subjects. Subcutaneous abdominal
      adipose tissue underwent biochemical and molecular biology analyses, aimed at
      testing the expression of this system and its functional activity. AEA and 2-AG
      levels were detected and quantified by HPLC. Real time PCR analyzed the
      expression of the endocannabinoid system and immunofluorescence assays showed the
      distribution of its components in the adipose tissue. Furthermore, binding assay
      for the cannabinoid and vanilloid receptors and activity assay for each metabolic
      enzyme of the endocannabinoid system gave clear evidence of a fully operating
      system. The data presented herein show for the first time that the human adipose
      tissue is able to bind AEA and 2-AG and that it is endowed with the biochemical
      machinery to metabolize endocannabinoids.

PMID- 16949719
TI  - Available ventilation monitoring methods during pre-hospital cardiopulmonary
      resuscitation.
AB  - High quality cardiopulmonary resuscitation (CPR) in the pre-hospital setting has
      been associated with improved survival rates during cardiopulmonary arrest (CPA).
      Recent documentation of hyperventilation associated deterioration in hemodynamics
      during CPR, suggests that guided or controlled ventilation strategies may
      contribute to improved hemodynamics and increased survival. This article briefly
      reviews the mechanical methods, advantages, and disadvantages of the available
      ventilation monitoring methods currently available for clinical use, with an
      emphasis on pre-hospital implementation. We recommend that more objective
      measurement of ventilation during CPR be performed, with emphasis on a strategy
      for measuring both attempted ventilation frequency (f) and delivered tidal volume
      (VT). The use of improved thoracic impedance pneumography and capnography are
      appealing for such monitoring because of the widespread availability, but
      modifications to existing software and clinical data compared to a clinical
      standard would be required before general acceptance is possible. Other methods
      listed may offer advantages over these in select circumstances.

PMID- 16949720
TI  - Umbilical cord plasma concentrations of free morphine following single-dose
      diamorphine analgesia and their relationship to dose-delivery time interval,
      Apgar scores and neonatal respiration.
AB  - OBJECTIVE: To find the effect of dose-delivery interval on cord-blood levels of
      diamorphine metabolites and its effect on Apgar sores and neonatal respiration.
      STUDY DESIGN: Pilot study conducted in labour ward of a district general
      hospital. One hundred women who had normal delivery and received single dose of
      7.5mg of intramuscular injection of diamorphine in labour were recruited in the
      study. A 2.0 ml sample of umbilical venous blood was collected from the placenta
      after delivery of the baby. The sample was analysed using RIA method to measure
      free morphine. Details about the labour and baby's condition at birth were
      recorded. RESULTS: The concentration of free morphine in the umbilical venous
      blood was significantly associated with the dose-delivery interval (coefficient
      (95% CI)=1.08(0.99-1.18), p<0.001). Twenty neonates had low Apgar score (< or =7)
      at 1 min. The odds of such a low score were raised with higher log free morphine
      in the cord venous plasma, but not statistically significantly (OR (95% CI)=5.3
      (0.84-34), p=0.08). Fourteen neonates required resuscitation. The odds of
      requiring resuscitation were significantly raised with higher log free morphine:
      OR (95% CI)=9.3 (1.0-86), p=0.05. CONCLUSION: Concentration of free morphine in
      the umbilical venous blood after delivery was significantly associated with the
      dose-delivery interval and this had significant effect on the need for
      resuscitation.

PMID- 16949722
TI  - Randomised controlled trial comparing three methods of presenting risk of Down's
      syndrome.
AB  - OBJECTIVE: To compare three simple methods of presenting information to patients
      about the risk of Down's syndrome. STUDY DESIGN: Randomised controlled trial of
      150 " low risk" women booking for antenatal care before 19 weeks gestation at
      Sunderland Royal Hospital. After informing the women about the purpose of the
      study and reassuring them that they were "low risk", each patient was given a
      questionnaire, which used one of three different methods (graphic, written and
      interactive) to present information about the risk of Down's syndrome. A visual
      analogue scale allowed us to assess their level of understanding and anxiety
      before and after the information about risk was given to them. RESULTS: All three
      methods significantly altered patients' perception and anxiety about the risk of
      Down's syndrome. The interactive method was found to be the most effective of the
      three. CONCLUSION: This pilot study suggests that discussing the patients'
      worries about fetal anomalies with medical staff can markedly reduce their degree
      of anxiety. The interactive method was most effective at putting information
      across to the patient. It significantly reduced their level of anxiety as well as
      their overall worry about pregnancy.

PMID- 16949723
TI  - In situ adenocarcinoma and squamous carcinoma of uterine cervix. Pathological and
      immunohistochemical analysis with cytokeratin 13.
AB  - OBJECTIVES: The aim of the study was the pathological and immunohistochemical
      analysis of cytokeratin 13 (CK13) in intraepithelial cervical tumors. STUDY
      DESIGN: We studied 415 in situ squamous carcinomas and 13 in situ mucinous
      cervical type adenocarcinomas of the uterine cervix. All patients underwent laser
      cervical conization and had a follow-up ranging 12-135 months. RESULTS: 3% of the
      squamous carcinoma patients recurred during the follow-up period, while the
      percentage of recurrence of in situ adenocarcinoma patients was 7.6%. We observed
      positive surgical edges in 46.1% of glandular tumors, and in 5% of squamous
      tumors. The percentage of recurrence was high among the cases with positive
      borders independently from their histopathologic type (14.3% in the squamous
      carcinomas versus 50% in the adenocarcinomas), compared to cases with negative
      edges (2.3% in the squamous carcinomas versus 0% in the adenocarcinomas). We
      observed CK13 positive staining in cervical squamous tumors and in mucinous
      cervical type adenocarcinomas, while there was no positive staining in non
      neoplastic cervical glandular elements. CONCLUSION: CK13 positive immunostaining
      among in situ squamous and in situ mucinous cervical type adenocarcinoma cases
      adds additional evidence to data supporting a common origin of the two lesions.

PMID- 16949724
TI  - Unexpected luteal endometrial decline in a healthy rural Polish population.

PMID- 16949725
TI  - Photophysics of ANS. III: Circular dichroism of ANS and anilinonaphthalene in I
      FABP.
AB  - We investigate the circular dichroism of the I-FABP system with the ligands ANS
      (1,8-anilinonaphthalene sulfonate) and AnN (anilinonaphthalene) as previously
      reported in our earlier publications in the series (referred to as I and II here)
      on ANS photophysics. We employ our semi-empirical calculated spectral functions
      (from II) to compute the actual CD spectra, without any additional assumptions or
      data except what we have previously presented with respect to binding geometry
      (in I). The common mechanisms fail to produce the observed spectra. However, we
      identify a novel mechanism of induced CD activity, which does succeed. This new
      mechanism also suggests how it is that near UV CD can often show extreme
      sensitivity to local 'order' effects.

PMID- 16949726
TI  - Effects of gas flow rate, inlet concentration and temperature on the
      biofiltration of toluene vapors.
AB  - In this work the variation in the elimination capacity of a biofilter as a
      function of the gas flow and toluene concentration was studied. A bioreactor 0.75
      m high x 14.5 cm diameter was used, divided into three equal stages, using
      compost to support the microorganisms, and sea shells to control the pH. The
      biofiltration of toluene was evaluated for flows between 0.12 and 0.73 m(3)h(-1)
      in a concentration range of 1-3.2 gm(-3). It was observed that on increasing the
      toluene inlet load by 90% (from 37 to 70 gm(3)h(-1)), the conversion by the
      biofilter varied by only 5% (from 98% to 93%). The biofiltration system used
      achieved elimination capacities of up to 82 gm(-3)h(-1) for a toluene load of 100
      gm(-3)h(-1).

PMID- 16949727
TI  - Environmental and human exposure assessment monitoring of communities near an
      abandoned mercury mine in the Philippines: a toxic legacy.
AB  - Abandoned mines are an important global concern and continue to pose real or
      potential threats to human safety and health including environmental damage/s.
      Very few countries had government mine regulation and reclamation policies until
      the latter part of the century where legal, financial and technical procedures
      were required for existing mining operations. Major reasons for mine closure may
      be mainly due to poor economies of the commodity making mining unprofitable,
      technical difficulties and national security. If the mine is abandoned, more
      often than not it is the government that shoulders the burden of clean-up,
      monitoring and remediation. The topic of abandoned mines is complex because of
      the associated financial and legal liability implications. Abandoned mercury
      mines have been identified as one of the major concerns because of their
      significant long-term environmental problems. Primary mercury production is still
      ongoing in Spain, Kyrgzystan, China, Algeria, Russia and Slovakia while world
      production declined substantially in the late 1980s. In the Philippines, the
      mercury mine located southeast of Manila was in operation from 1955 to 1976,
      before ceasing operation because of the decline in world market price for the
      commodity. During this time, annual production of mercury was estimated to be
      about 140,000 kg of mercury yearly. Approximately 2,000,000 t of mine-waste
      calcines (retorted ore) were produced during mining and roughly 1,000,000 t of
      these calcines were dumped into nearby Honda Bay to construct a jetty to
      facilitate mine operations where about 2000 people reside in the nearby three
      barangays. In October, 1994 the Department of Health received a request from the
      Provincial Health Office for technical assistance relative to the investigation
      of increasing complaints of unusual symptoms (e.g. miscarriages, tooth loss,
      muscle weakness, paralysis, anemia, tremors, etc.) among residents of three
      barangays. Initial health reports revealed significant elevation of blood mercury
      levels exceeding the then recommended exposure level of 20ppb in 12 out of the 43
      (27.9%) residents examined. The majority of the volunteers were former mine
      workers. In this study the abnormal findings included gingivitis, mercury lines,
      gum bleeding and pterydium. The most common neurologic complaints were numbness,
      weakness, tremors and incoordination. Anemia and elevated liver function tests
      were also seen in a majority of those examined. The assessment also revealed a
      probable association between blood mercury level and eosinophilia. The same
      association was also seen between high mercury levels and the presence of tremors
      and working in the mercury mine. To date, there are very limited environmental
      and health studies on the impact of both total and methylmercury that have been
      undertaken in the Philippines. Thus, this area of study was selected primarily
      because of its importance as an emerging issue in the country, especially
      regarding the combined effects of total and methylmercury low-dose and continuous
      uptake from environmental sources. At present the effects of total mercury
      exposure combined with MeHg consumption remain an important issue, especially
      those of low-dose and continuous uptake. Results of the study showed that four
      (4) species of fish, namely ibis, tabas, lapu-lapu and torsillo, had exceeded the
      recommended total mercury and methylmercury levels in fish (NV>0.5 microg/gf.w.,
      NV>0.3 microg/gf.w., respectively). Saging and kanuping also exceeded the
      permissible levels for methylmercury. Total and methylmercury in canned fish, and
      total mercury in rice, ambient air and drinking water were within the recommended
      levels, however, additional mercury load from these sources may contribute to the
      over-all body burden of mercury among residents in the area. Surface water
      quality at the mining area, Honda Bay and during some monitoring periods at
      Palawan Bay exceeded total mercury standards (NV>0.002 ng/mL). Soil samples in
      two sites, namely Tagburos and Honda Bay, exceeded the EPA Region 9 Primary
      Remediation Goal recommended values for total mercury for residential purposes
      (NV>23 mg/kg). The hand to mouth activity among infants and children is another
      significant route for mercury exposure. Statistically significant results were
      obtained for infants when comparing the results after one year of monitoring for
      methylmercury levels in hair for both exposed and control sub-groups. Likewise,
      comparing the initial and final hair methylmercury levels among pregnant
      women/mothers in the exposed group showed statistically significant (p<0.05)
      results. Comparing the exposed and control sub-groups' mercury hair levels per
      sub-group showed statistically significant results among the following: (a)
      initial and final total mercury hair levels among children, (b) initial and final
      methylmercury hair levels among children, (c) final total mercury hair levels
      among pregnant women, (d) initial and final total mercury hair levels among
      mothers, and (e) initial and final methyl hair levels among mothers.

PMID- 16949728
TI  - Perineal salvage prostatectomy for radiation resistant prostate cancer.
AB  - OBJECTIVES: No data are available on the use of perineal prostatectomy for
      salvage treatment of local recurrent prostate cancer after radiotherapy. Here we
      report on the clinical aspects and follow-up of salvage perineal prostatectomy.
      MATERIALS AND METHODS: Twenty-seven patients underwent a perineal salvage
      prostatectomy from 1997-2005 for biopsy-proven local recurrent prostate cancer
      after external beam (n=22) or brachyradiotherapy (n=5). Staging included physical
      examination, prostate-specific antigen (PSA), transrectal ultrasound, computed
      tomography scan, and bone scan. RESULTS: Mean PSA before surgery was 8.6 ng/ml
      (+/-2.8 ng/ml). Comparing clinical staging with final pathologic staging after
      salvage perineal prostatectomy showed a 67% clinical understaging. Mean blood
      loss was 677 cc, and perioperative morbidity consisted of prolonged anastomotic
      leakage (n=8), urosepsis (n=3), prolonged hematuria (n=3), urinary retention
      (n=2), and rectal perforation (n=1). One patient died during the postoperative
      course because of urosepsis and endocarditis. At an interval of at least 12 mo
      after surgery, 37% (10 of 27) and 7% (2 of 27) of patients reported normal
      continence and erectile function, respectively. Five patients died during a mean
      follow-up of 43 mo; two patients died of prostate cancer. Five-year biochemical
      recurrence-free survival was 31% (95%CI, 25-42%). In a multivariate Cox
      regression analysis the serum PSA and PSA doubling time (PSADT) at the time of
      surgery were the best predictors of biochemical recurrence-free survival. No
      patient with a PSA>2 ng/ml and a PSADT<12 mo was without biochemical recurrence 2
      yr after surgery. CONCLUSIONS: Salvage perineal prostatectomy showed functional
      results that favorably compare with the retropubic approach, but considerable
      morbidity is still frequent. Proper patient selection therefore is mandatory. A
      serum PSA level of >2 ng/ml and PSADT<12 mo independently predict shorter
      biochemical recurrence-free survival.

PMID- 16949729
TI  - Vardenafil duration of action.

PMID- 16949730
TI  - Ureteral reimplantation for management of ureteral strictures: a retrospective
      comparison of laparoscopic and open techniques.
AB  - OBJECTIVES: To compare the results of laparoscopic ureteral reimplantation with a
      previous series of open surgery. MATERIALS AND METHODS: We compared ten patients
      who underwent laparoscopic vesicopsoas-hitch with (n=4) or without Boari-flap
      (n=6) technique for ureteral obstructions with ten patients treated by open
      ureteroneocystostomy for similar pathologies. Patient demographics, preoperative
      symptoms, radiologic imaging, and postoperative outcomes were analyzed.
      Postoperative observation time averaged 17 mo (range: 9-23) in the laparoscopic
      and 65 mo (range: 18-108) in the open group. Success was defined as relief of
      obstruction in postoperative imaging studies and relief of pain. RESULTS: Mean
      length of stricture (28.5 vs. 25 mm) was comparable in both groups. In
      laparoscopy versus open surgery, mean operative time (228 vs. 187 min) was
      longer, blood loss (370 vs. 610 ml) and analgesic requirement (4.9 vs. 21.5mg)
      were significantly lower, and mean time to oral intake (1.5 vs. 2.9 d), hospital
      stay (9.2 vs. 19.1 d), and convalescence time (2.3 vs. 4.2 wk) were significantly
      shorter. Success rates yielded 10 of 10 after laparoscopy and 8 of 10 after open
      surgery. No intra- or postoperative major complications occurred in the
      laparoscopic series. After open surgery, two patients had major postoperative
      complications, including urinary extravasation with abdominal haematoma and
      anastomostic stricture, respectively. CONCLUSIONS: Laparoscopic
      ureteroneocystostomy is feasible, providing functional outcomes comparable to
      open surgery while offering the advantages of a minimal invasive technique (e.g.,
      less postoperative analgesics, and shorter hospitalization and convalescence).
      Nevertheless, it requires a high level of laparoscopic expertise and should be
      carried out only in specialist centers.

PMID- 16949731
TI  - p16INK4a expression and clinicopathologic parameters in renal cell carcinoma.
AB  - OBJECTIVES: The tumour suppressor gene p16INK4a is a cyclin-dependent kinase
      inhibitor, for which inactivation attributable to promoter hypermethylation or
      homozygous deletion has been described in malignancies. Little is known about
      p16INK4a protein levels in renal cell carcinoma (RCC) and its association with
      clinicopathologic parameters or disease progression. METHODS: The expression of
      the p16INK4a gene was analysed with the use of immunohistochemistry and tissue
      microarrays (TMA). Tissue cores were obtained from the primary tumour itself, the
      tumoural invasion front, and histologically benign peritumoural tissue of 397
      nephrectomies. For statistical analysis, sections were classified into four
      groups according to the relative amount of positively stained cells: negative
      (0%), low (1-10%), intermediate (11-50%), and high positivity (>50%). Follow-up
      data were analyzed for 198 patients (follow-up period: 2-240 mo; median: 138 mo).
      RESULTS: Absent or low expression of p16INK4a was observed in 82% of tumour
      samples. No statistically significant association was found between protein
      levels detected in tumour, invasion front, or normal renal tissues and any of the
      clinicopathologic variables. Survival analysis by Kaplan-Meier revealed a
      significant association between high expression (>50%) of p16INK4a in tumours and
      better disease-specific survival (p=0.03, log-rank test). Cox regression analysis
      showed that p16INK4a expression is an independent covariate in disease-specific
      survival (p<0.01). CONCLUSIONS: The absence of p16INK4a expression in most tumour
      cells indicates that p16INK4a could be involved in the tumourigenesis of RCC.
      Immunohistochemically detected positivity for p16INK4a is a positive
      prognosticator for specific survival in both uni- and multivariate analyses.

PMID- 16949732
TI  - Multiple androgen response elements cooperate in androgen regulated activity of
      the type 1 neutral endopeptidase promoter.
AB  - The neutral endopeptidase (NEP) gene is transcriptionally regulated by androgen
      in prostate cancer cells. We previously identified in the NEP gene an androgen
      responsive element (NEP-ARE) and an androgen responsive region (NEP-ARR) that
      together conveyed only moderate androgen-inducibility [Mol. Cell. Endocrinol. 170
      (2000) 131]. Therefore, we characterized the entire genomic structure of the NEP
      gene and identified ARE1 (ACTCAACAttgTGTCCTTT) and ARE2 (CAGGACAtttTGTCCC), which
      are located in the 3'-untranslated region and in intron 17, respectively. Steroid
      dependent enhancement of transcription was assayed by transfecting the pGL-3
      luciferase reporter plasmid containing three copies of ARE1 or ARE2 into PC-3
      cells. Luciferase activities were increased 3.6-fold (ARE1) and 5-fold (ARE2) by
      androgen (AR), 4.2-fold (ARE1) and 8.2-fold (ARE2) by dexamethasone, and 3-fold
      (ARE1) and 4.1-fold (ARE2) by progesterone. Mutation of the ARE1 and ARE2
      sequences completely abrogated androgen-inducibility. We next showed that both
      ARE1 and ARE2 are involved in the transcriptional regulation of the NEP gene,
      demonstrating in vitro and in vivo binding with AR as determined by
      electrophoretic mobility gel shift and chromatin immunoprecipitation (ChIP)
      assays, Furthermore, ARE1 and ARE2 mediate coordinated androgen-inducibility in
      both an SV40 promoter and the native NEP type 1 promoter. These data indicate the
      newly identified ARE1 and ARE2 together with the previously identified NEP-ARE
      function as androgen response elements, and that androgen regulation of the NEP
      gene is regulated by the coordinated action of multiple AREs in prostate cancer
      cells.

PMID- 16949733
TI  - Treatment of drug-induced psychosis in Parkinson's disease with ziprasidone can
      induce severe dose-dependent off-periods and pathological laughing.
AB  - "Atypical anti-psychotics" are substances of choice in treating drug-induced
      psychosis (DP) in Parkinson's disease (PD). We report on four patients with DP
      who received treatment with ziprasidone after previously applied clozapine and
      quetiapine had failed. Three patients showed a significant improvement of DP,
      without deterioration of motor function. In one case, ziprasidone considerably
      increased decline in off-periods. Two patients developed pathological laughing as
      a possible side-effect of ziprasidone. Ziprasidone may serve as an additional
      "atypical anti-psychotic" for the treatment of DP in PD but can also induce
      deterioration of motor function.

PMID- 16949734
TI  - The relationship between Glasgow coma/outcome scores and abnormal CT scan
      findings in chronic subdural hematoma.
AB  - OBJECTIVES: Chronic subdural hematoma (CSDH) is one of the most frequent types of
      intracranial hemorrhage. We evaluated the independent association between
      abnormal CT findings in CSDH and both Glasgow coma score (GCS) on admission as a
      measure of consciousness and Glasgow outcome score (GOS) at discharge as a
      measure of outcome. PATIENTS AND METHODS: One hundred and sixteen consecutive
      patients with CSDH were studied. The variables considered were brain atrophy,
      hydrocephalus, hematoma location, midline shift, and hematoma density. After
      univariate analysis and evaluation of the role of age as a confounder in
      bivariate analysis, variables that had significant association with Glasgow
      scores were included in the final multivariate model. RESULTS: Brain atrophy was
      the only variable with significant independent association (p<0.001; OR=77.214;
      95% CI=8.336-715.212) with unfavorable outcome as defined by GOS. On the other
      hand, hydrocephalus (p=0.042; OR=6.503; 95% CI=1.072-39.449) and higher hematoma
      densities (p=0.027; OR=2.597; 95% CI=1.116-6.024) independently and significantly
      increased the risk of severe consciousness impairment when the group with GCS>12
      was considered as the reference category. CONCLUSION: Brain atrophy independently
      increases the risk of unfavorable outcome after CSDH. Hydrocephalus and higher
      hematoma densities independently increase the risk of severe consciousness
      impairment after CSDH.

PMID- 16949735
TI  - Corticosteroid-induced osteoporosis in neurology patients.

PMID- 16949736
TI  - Resistance to imatinib mesylate in chronic myeloid leukaemia.
AB  - Despite the remarkable results achieved with imatinib for the treatment of
      chronic myeloid leukaemia, the emergence of resistance to this tyrosine kinase
      inhibitor has become a significant problem. Much progress has been recently made
      in elucidating the mechanisms which underlie imatinib resistance. The most common
      cause of such drug resistance is the selection of leukaemic clones with point
      mutations in the Abl kinase domain leading to amino acid substitutions which
      prevent the appropriate binding of the drug. Other mechanisms include genomic
      amplification of BCR-ABL and modulation of drug efflux or influx transporters.
      There is a pressing need, therefore, to develop and test novel drugs and
      strategies. Two such compounds are now being explored in clinical trials. This
      review will describe the molecular basis of imatinib-resistance and strategies to
      overcome resistance.

PMID- 16949737
TI  - Removal of fluoride from water using anion-exchange membrane under Donnan
      dialysis condition.
AB  - The transport of fluoride through Neosepta-ACM anion-exchange membrane has been
      studied as a function of feed phase and receiver phase concentration and co
      existence anions under Donnan dialysis condition. It was observed that the
      transport of fluoride was maximum at pH 6 of feed phase and at pH 1 of receiver
      phase. Moreover, transport of fluoride increased with increase of feed and
      receiver phase concentration and decreased in the presence of other co-existence
      anions in the feed phase. The transport of fluoride was also correlated with the
      flux data and explained according to structure of membrane.

PMID- 16949738
TI  - Performance evaluation of a mesophilic (37 degrees C) upflow anaerobic sludge
      blanket reactor in treating distiller's grains wastewater.
AB  - The performance of a laboratory-scale upflow anaerobic sludge blanket (UASB)
      reactor treating distiller's grains wastewater was investigated for 420 days at
      37 degrees C. After a successful start-up, 80-97.3% chemical oxygen demand (COD)
      removal efficiencies were achieved at hydraulic retention times (HRT) of 82-11h
      with organic loading rates (OLR) of 5-48.3kgCODm(-3)d(-1). The biogas mainly
      consisted of methane and carbon dioxide, and the methane and carbon dioxide
      content in the biogas was 57-60 and 38-41%, respectively. The yield coefficient
      of methane production was 0.3182lCH(4)g(-1)COD removed until OLR at 33.3kgCODm(
      3)d(-1), but afterwards began to decrease. The volatile fatty acid (VFA) in the
      effluent mainly consisted of acetate and propionate, accounting for more than 95%
      of total VFA as COD, and other VFA was detected at insignificant concentrations.
      The mesophilic granules developed in this study showed an excellent specific
      methanogenic activity (SMA) at 0.91 and 1.12gmethaneCODg(-1)VSS(-1)d(-1) using
      sucrose and acetate as individual substrates on day 200, respectively.

PMID- 16949739
TI  - Preparation and application of granular ZnO/Al2O3 catalyst for the removal of
      hazardous trichloroethylene.
AB  - Trichloroethylene (TCE) is a volatile and nerve-toxic liquid, which is widely
      used in many industries as an organic solvent. Without proper treatment, it will
      be volatilized into the atmosphere easily and hazardous to the human health and
      the environment. This study tries to prepare granular ZnO/Al(2)O(3) catalyst by a
      modified oil-drop sol-gel process incorporated the incipient wetness impregnation
      method and estimates its performance on the catalytic decomposition of TCE. The
      effects of different preparation and operation conditions are also investigated.
      Experimental results show that the granular ZnO/Al(2)O(3) catalyst has good
      catalytic performance on TCE decomposition and the conversion of TCE is 98%.
      ZnO/Al(2)O(3)(N) catalyst has better performance than ZnO/Al(2)O(3)(O) at high
      temperature. Five percent of active metal concentration and 550 degrees C
      calcination temperature are the better and economic preparation conditions, and
      the optimum operation temperature and space velocity are 450 degrees C and 18,000
      h(-1), respectively. The conversions of TCE are similar and all higher than 90%
      as the oxygen concentration in feed gas is higher than 5%. By Fourier transform
      infrared spectrography (FT-IR) analyses, the major reaction products in the
      catalytic decomposition of TCE are HCl and CO(2). The Brunauer-Emmett-Teller
      (BET) surface areas of catalysts are significantly decreased as the calcination
      temperature is higher than 550 degrees C due to the sintering of catalyst
      materials, as well as the reaction temperature is higher than 150 degrees C due
      to the accumulations of reaction residues on the surfaces of catalysts. These
      results are also demonstrated by the results of scanning electron micrography
      (SEM) and energy disperse spectrography (EDS).

PMID- 16949740
TI  - Comparative study on reaction selectivity of azo dye decolorization by
      Pseudomonas luteola.
AB  - This study is to inspect how the variation of molecular structures and functional
      groups present in our model azo dyes (i.e., Congo red, Eriochrome black T (EBT),
      methyl orange, and methyl red) affects biodecolorization capability of
      Pseudomonas luteola. The most viable decolorization was found at pH 7-9 and the
      optimal cellular age for the most effective decolorization was 7 days after
      static incubation in dye-free cultures. In decolorization, the maximal absorption
      wavelength in UV-vis spectra for the different dye-containing cultures shifted
      from visible light range towards the ultraviolet visible range. Methyl red was
      not decolorized in contrast to methyl orange, Congo red, and Eriochrome black T.
      The sulfonic group para to azo bond (-N=N-) in methyl orange was a strong
      electron-withdrawing group through resonance to cause an enhancement of color
      removal to be easily biodecolorized. As a charged carboxyl group on methyl red is
      at ortho position (i.e., in the proximity) to azo bond, this led to a complete
      inhibition to decolorization. However, decolorization of Congo red and EBT in the
      absence of charged group (e.g., hydroxy or amino group) near azo bond was not
      completely repressed like methyl red. Thus, the presence of electron-withdrawing
      groups as the substituents on azo dyes enhanced decolorization capability for
      biodegradability. In addition, Monod kinetic model provided better predictions to
      all dye decolorization at initial short periods of time due to negligible
      intermediate formed at initial short time duration, but significant intermediate
      accumulation took place at longer period of time. In contrast, the decolorization
      performances of methyl orange at 400ppm and EBT at 230ppm were significantly less
      than those predicted from the Monod kinetic model likely due to accumulated
      intermediates exceeding the threshold levels for feedback inhibition.

PMID- 16949741
TI  - On-line preconcentration and determination of mercury in biological and
      environmental samples by cold vapor-atomic absorption spectrometry.
AB  - An on-line procedure for the determination of traces of total mercury in
      environmental and biological samples is described. The present methodology
      combines cold vapor generation associated to atomic absorption spectrometry (CV
      AAS) with preconcentration of the analyte on a minicolumn packed with activated
      carbon. The retained analyte was quantitatively eluted from the minicolumn with
      nitric acid. After that, volatile specie of mercury was generated by merging the
      acidified sample and sodium tetrahydroborate(III) in a continuous flow system.
      The gaseous analyte was subsequently introduced via a stream of Ar carrier into
      the atomizer device. Optimizations of both, preconcentration and mercury volatile
      specie generation variables were carried out using two level full factorial
      design (2(3)) with 3 replicates of the central point. Considering a sample
      consumption of 25mL, an enrichment factor of 13-fold was obtained. The detection
      limit (3sigma) was 10ngL(-1) and the precision (relative standard deviation) was
      3.1% (n=10) at the 5microgL(-1) level. The calibration curve using the
      preconcentration system for mercury was linear with a correlation coefficient of
      0.9995 at levels near the detection limit up to at least 1000microgL(-1).
      Satisfactory results were obtained for the analysis of mercury in tap water and
      hair samples.

PMID- 16949742
TI  - Determination of insecticide pymetrozine by differential pulse
      polarography/application to lake water and orange juice.
AB  - A simple, fast and sensitive differential pulse polarographic method (DPP) for
      the determination of pymetrozine insecticide in pure form, agrochemical
      formulation, natural water and orange juice samples is proposed. The
      polarographic behavior of pymetrozine exhibited a double well-defined
      polarographic peaks at -580 and 950mV (versus SCE), respectively. The peak
      potentials were strongly pH-dependent in that they shifted to more negative
      values with increasing pH. The polarographic reduction corresponding to the first
      peak at pH 2.0 (B-R buffer solution) showed quantitative increments with the
      additions of standard pymetrozine solution under the optimal conditions and the
      corresponding peak current was linearly proportional to pymetrozine concentration
      in the range of 4.97x10(-7) to 7.35x10(-5)molL(-1). The limit of detection (LOD)
      and limit of quantification (LOQ) were obtained as 1.48x10(-7) and 4.93x10(
      7)molL(-1), respectively. The mean recoveries of the 5.0x10(-6)molL(-1)
      pymetrozine spiked to lake water and orange juice were (4.89+/-0.23)x10(-6) and
      (4.97+/-0.19)x10(-6)molL(-1) at 95% confidence level, respectively. The method
      was extended to the determination of pymetrozine in agrochemical insecticide
      formulation Plenum and accuracy was in agreement with that obtained by HPLC
      comparison method. Influences of some interfering ions and some other pesticides
      were also investigated. The mechanistic study was not pursued.

PMID- 16949743
TI  - Relation between some two- and three-parameter isotherm models for the sorption
      of methylene blue onto lemon peel.
AB  - Equilibrium uptake of methylne blue onto lemon peel was fitted to the 2 two
      parameter isotherm models namely Freundlich and Langmuir and 3 six-parameter
      isotherm models namely Redlich-Peterson, Toth, Radke-Prausnitz, Fritz-Schluender,
      Vieth-Sladek and Sips isotherms by non-linear method. A comparison between two
      parameter and three-parameter isotherms was reported. The best fitting isotherm
      was the Sips isotherm followed by Langmuir isotherm and Redlich-Peterson isotherm
      equation. Redlich-Peterson isotherm is a special case of Langmuir isotherm when
      the Redlich-Peterson isotherm constant g was unity. Radke-Prausnitz, Toth, Vieth
      Sladek isotherm were the same when the Toth isotherm constant, n(T) and the Radke
      Prausnitz isotherm, m(RP) are equal to unity and when the Vieth-Sladek isotherm
      constant, K(VS) equals zero. The sorption capacity of lemon peel for methylene
      blue uptake was found to be 29 mg/g.

PMID- 16949744
TI  - Calorimetric studies on the thermal hazard of methyl ethyl ketone peroxide with
      incompatible substances.
AB  - In Taiwan, Japan, and China, methyl ethyl ketone peroxide (MEKPO) has caused many
      severe thermal explosions owing to its thermal instability and reactivity
      originating from the complexity of its structure. This study focused on the
      incompatible features of MEKPO as detected by calorimetry. The thermal
      decomposition and runaway behaviors of MEKPO with about 10wt.% incompatibilities,
      such as H(2)SO(4), HCl, NaOH, KOH, FeCl(3), and FeSO(4), were analyzed by dynamic
      calorimeter, differential scanning calorimetry (DSC) and adiabatic calorimeter,
      vent sizing package 2 (VSP2). Thermokinetic data, such as onset temperature, heat
      of decomposition, adiabatic temperature rise, and self-heat rate, were obtained
      and assessed. Experimental data were used for determining the incompatibility
      rating on hazards. From the thermal curves of MEKPO with assumed incompatible
      substances detected by DSC, all the onset temperatures in the other tests
      occurring earlier advanced, especially with alkaline or ferric materials. In some
      tests, significant incompatible reactions were found. Adiabatic runaway behaviors
      for simulating the worst case scenario were performed by using VSP2. These
      calorimetric data led to the same results that the alkaline or ferric solution
      was the most incompatible with MEKPO.

PMID- 16949745
TI  - Use of carbon stable isotope to investigate chloromethane formation in the
      electrolytic dechlorination of trichloroethylene.
AB  - Carbon stable isotope trichloroethylene ((13)C TCE) was used to investigate the
      formation of chloromethane (CM) during the electrolytic dechlorination of
      trichloroethylene (TCE) at a granular-graphite packed cathode. A method was
      developed to use a conventional GC/MS to analyze and quantify regular and (13)C
      TCE and their dechlorination products. The concentration of a (13)C compound can
      be calculated, based on the concentration of its regular counterpart, from the
      response ratio of two fragments of different mass per charge values from the
      compounds in a sample and two characteristic MS spectrum ratios: one is the
      response ratio of the two fragments of the regular compound, and the other is the
      response ratio of the corresponding fragments of the regular and (13)C compounds
      at the same concentrations. The method was used to analyze the regular and (13)C
      compounds observed in an experiment of dechlorination in an ammonium acetate
      solution that contained both regular TCE and (13)C TCE. Results of analysis
      confirmed that CM was not a direct product of TCE dechlorination at the granular
      graphite cathode that cis-DCE was an intermediate product of TCE dechlorination,
      and that 1,1-DCE was not a dechlorination product.

PMID- 16949746
TI  - Use of potassium dihydrogen phosphate and sawdust as adsorbents of ammoniacal
      nitrogen in aerobic composting process.
AB  - Three kinds of adsorbents-potassium dihydrogen phosphate, sawdust and mixture of
      potassium dihydrogen phosphate and sawdust were added respectively into
      composting to investigate their adsorption effect on ammonia. The experimental
      results showed that all the adsorbents could restrain ammonia volatilizing, with
      the sorption of potassium dihydrogen phosphate adsorbents being the best of all,
      the sorption of mixture adsorbent with potassium dihydrogen phosphate and sawdust
      being the second and the sorption of sawdust adsorbent being the last. Therefore,
      the total nitrogen loss ratios respectively reduced from 38% to 13%, 15% and 21%
      after adding these three kinds of adsorbents into composting. However, potassium
      dihydrogen phosphate produced negative influence on composting properties as its
      supplemented amount exceeded a quantity basis equivalent to 18% of total nitrogen
      in the composting, for example: pH value had been lessened, microorganism
      activity reduced, which finally resulted in the reduction of biodegradation ratio
      of organic matter. But it did not result in these problems when using the mixture
      of potassium dihydrogen phosphate and sawdust as adsorbent, in which the amount
      of potassium dihydrogen phosphate was under a quantity basis equivalent to 6% of
      total nitrogen in the composting. Moreover, the mixture adsorbent produced better
      adsorption effect on ammonia, and raised biodegradation ratio of organic matter
      from 26% to 33%.

PMID- 16949747
TI  - Repeated intrathecal injections of plasmid DNA encoding interleukin-10 produce
      prolonged reversal of neuropathic pain.
AB  - Neuropathic pain is a major clinical problem unresolved by available
      therapeutics. Spinal cord glia play a pivotal role in neuropathic pain, via the
      release of proinflammatory cytokines. Anti-inflammatory cytokines, like
      interleukin-10 (IL-10), suppress proinflammatory cytokines. Thus, IL-10 may
      provide a means for controlling glial amplification of pain. We recently
      documented that intrathecal IL-10 protein resolves neuropathic pain, albeit
      briefly (approximately 2-3 h), given its short half-life. Intrathecal gene
      therapy using viruses encoding IL-10 can also resolve neuropathic pain, but for
      only approximately 2 weeks. Here, we report a novel approach that dramatically
      increases the efficacy of intrathecal IL-10 gene therapy. Repeated intrathecal
      delivery of plasmid DNA vectors encoding IL-10 (pDNA-IL-10) abolished neuropathic
      pain for greater than 40 days. Naked pDNA-IL-10 reversed chronic constriction
      injury (CCI)-induced allodynia both shortly after nerve injury as well as 2
      months later. This supports that spinal proinflammatory cytokines are important
      in both the initiation and maintenance of neuropathic pain. Importantly, pDNA-IL
      10 gene therapy reversed mechanical allodynia induced by CCI, returning rats to
      normal pain responsiveness, without additional analgesia. Together, these data
      suggest that intrathecal IL-10 gene therapy may provide a novel approach for
      prolonged clinical pain control.

PMID- 16949748
TI  - Tramadol, fentanyl and sufentanil but not morphine block voltage-operated sodium
      channels.
AB  - Lidocaine-like sodium channel blocking drugs provide pain relief either by
      interrupting impulse conduction in neurons when applied locally in high
      concentrations or, when given systemically, by suppressing high-frequency ectopic
      discharges due to preferential drug binding to inactivated channel states.
      Lidocaine-like actions of opioids have frequently been demonstrated clinically.
      However, drug binding to resting and inactivated channel conformations has been
      studied systematically only in the case of meperidine. The aim of this in vitro
      study was to investigate the effects of four currently used opioids on
      heterologously expressed neuronal (NaV(1.2)) voltage-gated sodium channels. Block
      of sodium currents was studied at hyperpolarized holding potentials and at
      depolarized potentials inducing either fast- or slow-inactivation. Sufentanil,
      fentanyl and tramadol but not morphine reversibly suppressed sodium inward
      currents at high concentrations (half-maximum blocking concentrations (IC50) 49+/
      4, 141+/-6 and 103+/-8 microM) when depolarizations were started from
      hyperpolarized holding potentials. Short depolarizations inducing fast
      inactivation and long prepulses inducing slow-inactivation significantly (*p < or
      = 0.001) increased the blocking potency for these opioids. 15% slow inactivated
      channels reduced the respective IC50 values to 5+/-3, 12+/-2 and 21+/-2 microM.
      These results show that: (1) Sufentanil, fentanyl and tramadol block voltage
      gated sodium channels with half-maximum inhibitory concentrations similar to the
      IC50 reported for meperidine. (2) Slow inactivation--a physiological mechanism to
      suppress ectopic activity in response to slow shifts in membrane potential-
      increases binding affinity for sufentanil, fentanyl and tramadol. (3) Morphine
      has no such effects.

PMID- 16949751
TI  - Persistent pain and uncomfortable sensations in persons with multiple sclerosis.
AB  - The experience of pain has been documented in small studies of individuals with
      multiple sclerosis (MS). The present study examines the prevalence of persistent
      pain and uncomfortable sensations among participants in the large North American
      Research Committee on MS (NARCOMS) Patient Registry. Registrants (10,176)
      responded to a questionnaire on pain and 7579 reported experiencing some level of
      pain during the month prior to the survey. Among the respondents 49% reported
      mild to severe pain and 49% of those indicated severe pain. Increased pain
      intensity was positively associated with gender (more women), multiple pain sites
      (51% of the severe pain group reported four or more pain sites), and constancy of
      pain (44% among the group with severe pain). There was also a positive
      association with increased MS-related disability, relapsing-worsening type of MS,
      and depression. Respondents with severe pain made greater use of the healthcare
      system and of prescribed analgesics, but were less likely to be satisfied with
      their doctors' efforts to manage their pain. About one-third of the patients with
      moderate pain and 18% of those with severe pain reported no consultations for
      their pain. The effects of pain severity were fully evident in the respondents'
      daily life, their work, mood, recreational activities and enjoyment of life. Our
      results indicate that the high prevalence of MS-related severe pain, low
      satisfaction with management of intense pain, and the perceived interference with
      quality of life indicators necessitate greater attention by healthcare providers
      to the management of pain and uncomfortable sensations in the MS population.

PMID- 16949753
TI  - Pain assessment in profound cognitive impaired children using the Checklist Pain
      Behavior; is item reduction valid?
AB  - There are both commonalities and idiosyncratic features in the reaction of pain
      children with profound cognitive impairment (CI), and that there is no evidence
      to suggest that idiosyncratic behavior is more characteristic of this population
      than of any other population. The main objective of this study was to identify
      whether the 23-item version of the Checklist Pain Behavior could be reduced to 10
      items. Previous research demonstrated that only these 10 items discriminated
      between absence and presence of pain. Second, we wanted to explore the underlying
      structure of these 10 selected items including its performance. Data of 477
      observations in 73 children were used. All these children were video-taped while
      they were admitted to the Sophia Children's Hospital for surgery, twice before
      and five times after surgery. These video-tapes were scored by an independent
      observer. A visual analogue scale (VAS) by a researcher was used to assess the
      presence of pain. We tested whether the underlying structure was unidimensional,
      and whether it had differential qualities between pain and no pain, and to which
      degree. Using a modern psychometric method, i.e., Mokken scaling model, we
      unraveled the interdependency of the pain response in CI-children, in that the
      structure turned out to be unidimensional. In addition, these behaviors could be
      hierarchically ordered in terms of frequency of occurrences. Finally, these
      behaviors had to a high degree the potentialities to estimate the likelihood of
      occurrence of pain.

PMID- 16949754
TI  - Real-time imaging of DNA-streptavidin complex formation in solution using a high
      speed atomic force microscope.
AB  - The direct observation of individual molecules in action is required for a better
      understanding of the mechanisms of biological reactions. We used a high-speed
      atomic force microscope (AFM) in solution to visualize short DNA fragments in
      motion. The technique represents a new approach in analyzing molecular
      interactions, and it allowed us to observe real-time images of biotinylated DNA
      binding to/dissociating from streptavidin protein. Our results show that high
      speed AFMs have the potential to reveal the mechanisms of molecular interactions,
      which cannot be determined by analyzing the average value of mass reactions.

PMID- 16949755
TI  - Optimizing phase contrast in transmission electron microscopy with an
      electrostatic (Boersch) phase plate.
AB  - Imaging of weak amplitude and phase objects, such as unstained vitrified
      biological samples, by conventional transmission electron microscopy (TEM)
      suffers from poor object contrast since the amplitude and phase of the scattered
      electron wave change only very little. In phase contrast light microscopy the
      imaging of weak phase objects is greatly enhanced by the use of a quarter-wave
      phase plate, which produces high signal contrast by shifting the phase of the
      scattered light. An analogous quarter-wave plate for the electron microscope,
      designed as an electrostatic einzel lens, was proposed by Boersch in 1947 but the
      small dimensions of the device have impeded its realization up to now. We here
      present the first fabrication and application of a miniaturized electrostatic
      einzel lens driven as TEM quarter-wave phase plate. Phase modulation is generated
      by the electrostatic field confined to the inside of a microstructured ring
      electrode. This field affects the phase velocity of the unscattered part of the
      electron wave. By varying its strength the phase shift of the primary beam can be
      adjusted to pi/2, producing strong phase contrast independent of spatial
      frequency. The phase plate proves to be mechanically stable and does not impair
      image quality, in particular it does not reduce the high-resolution signal. The
      expected residual lens effect of the einzel lens is minimal. Our microlens is
      supported by conducting rods arranged in a threefold symmetry. This particular
      geometry provides optimized single-sideband signal transfer for spatial
      frequencies otherwise obstructed by the supporting rods.

PMID- 16949756
TI  - PKC inhibition is involved in trichosanthin-induced apoptosis in human chronic
      myeloid leukemia cell line K562.
AB  - Trichosanthin (TCS), a type I ribosome-inactivating protein, induces cell death
      in various cell types including several tumor cell lines. However, the mechanism
      remains largely uncharacterized. In this study, we investigated the possible
      mechanism underlying its cytotoxicity by using human chronic myeloid leukemia
      cell line K562. We found that TCS induced apoptosis in K562 cells in a time- and
      concentration-dependent manner and can be blocked by caspase-3 inhibitors.
      Interestingly, TCS treatment induced a transient elevation in intracellular
      calcium concentration and a slow increase in reactive oxygen species production,
      while calcium chelators and antioxidants had no obvious effect on TCS-induced
      apoptosis, suggesting that calcium changes and reactive oxygen species may not be
      involved in TCS-mediated apoptosis in K562 cells. Instead we found that TCS
      partly inhibited PKC activity. Indeed, the PKC activator, PMA, inhibited while
      the PKC inhibitor, calphostin c, enhanced TCS-induced apoptosis. These PKC
      modulators had similar effects on TCS-induced cleavage of caspase-3, and caspase
      3 inhibitors prevented calphostin c-enhanced apoptosis induced by TCS. In
      summary, we conclude that TCS induces apoptosis in K562 cells partly via PKC
      inhibition and caspase-3 activation.

PMID- 16949757
TI  - Specific peptide patterns of follicular fluids at different growth stages
      analyzed by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry.
AB  - Human follicular fluid (HFF) has been suggested to influence oocyte development
      potential, and some of HFF proteins may be potential markers for oocyte
      maturation during follicular development. Using matrix-assisted laser desorption
      /ionization-time of flight mass spectrometry (MALDI-TOF MS), the presence of
      specific peptide peaks in HFF which could represent the follicle development
      potential was evaluated. HFF from different developmental stages were first
      digested and the resultant peptide mixtures were directly analyzed by MALDI-TOF
      MS. It was shown that the frequencies of specific peaks demonstrated higher
      reproducibility than peak intensities after multiple measurements (>or=6 times)
      per sample. Using this approach, a reliable peak list for each different sample
      could be generated by combining the information from multiple measurements. By
      comparing the peak lists from different samples at different growth stages, we
      found that 5 specific peaks appeared in the 100% frequency category of 6
      replicates in all the HFF samples containing mature oocyte. Similarly, such 25
      peptide peaks were also identified for HFF containing immature oocyte. These
      specific peaks could be used to distinguish HFF from different stages as
      biomarkers related to follicle development and maturation. After searching the
      protein database, some proteins that are known to be involved in the development
      and maturation of oocyte were identified, such as apolipoprotein A-I, collagen
      type IV, integrin, et al. Identification of such proteins in our experiment
      further proved that the direct analysis of tryptic digests could be of practical
      value.

PMID- 16949758
TI  - The endocrine regulation of milk lipid synthesis and secretion in tammar wallaby
      (Macropus eugenii).
AB  - Lipids in tammar milk are predominantly triacylglycerols, and the fatty acid
      composition varies during the lactation cycle. Little is known about the
      regulation of their synthesis. This study investigates the endocrine regulation
      of lipid synthesis in mammary explants from pregnant tammars. Treatment of
      mammary explants with insulin resulted in a high level of lipid synthesis, but
      the lipids accumulated in the cytosol. Culture with prolactin resulted in a small
      increase in lipid synthesis, but electron microscopy showed lipid globules were
      synthesized in the mammary epithelial cells and secreted into the lumen. Culture
      with both insulin and prolactin demonstrated elevated levels of synthesis and
      secretion of lipid. Analysis of the type of fatty acids synthesized in these
      mammary explants showed that the initiation of synthesis of C(16:0), which also
      occurs in the first week of lactation, could be reproduced in the pregnant
      explants cultured with prolactin alone. However, treatment of mammary explants
      with hydrocortisone did not show a significant effect on lipid synthesis,
      secretion or the fatty acid synthesized. These results provide new information
      identifying the role of insulin and prolactin in regulating milk lipid synthesis
      and secretion in the tammar.

PMID- 16949759
TI  - Nestin expression in Muller glial cells in postnatal rat retina and its
      upregulation following optic nerve transection.
AB  - This study examined the nestin immunoexpression and its specific cellular
      localization in the developing retina of rats and investigated its putative
      changes in an altered environment. At postnatal day 0, nestin immunoexpression
      was detected in radially oriented cells considered to be neural progenitors that
      were glutamine synthetase (GS) negative. With age, it was localized in
      differentiating and differentiated GS positive Muller glial cells. Nestin
      expression was down-regulated as maturation proceeded, so that by 12 weeks, it
      was almost completely diminished as confirmed also by real time-polymerase chain
      reaction analysis. Nestin expression along with that of glial fibrillary acidic
      protein (GFAP) was induced and upregulated in mature Muller glial cells following
      optic nerve transection. It is suggested that both nestin and GFAP may be useful
      biomarkers in retinal injuries. In view of their cytoskeletal nature, the marked
      expression of nestin and GFAP may provide a structural support for the framework
      of retina which would be disrupted as a result of loss of neurons in optic nerve
      lesion. It may also be neuronal protective taking into consideration the close
      spatial and functional links between Muller glial cells and the axotomized
      ganglion cells.

PMID- 16949760
TI  - Temporospatial coupling of networked synaptic activation of AMPA-type glutamate
      receptor channels and calcium transients in cultured motoneurons.
AB  - AMPA-type glutamate receptor (GluR) channels provide fast excitatory synaptic
      transmission in the CNS, but mediate also cytotoxic insults. It could be shown
      that AMPA-type GluR channel-mediated chronic excitotoxicity leads to an increased
      intracellular calcium concentration and plays an important role in
      neurodegenerative diseases like for example amyotrophic lateral sclerosis (ALS).
      As calcium is an important mediator of various processes in the cell and calcium
      signals have to be very precise in the temporospatial resolution, excessive
      intracellular calcium increases can seriously impair cell function. It is still
      unclear if AMPA-type receptors can directly interact with the intracellular
      calcium homeostasis or if other mechanisms are involved in this process. The
      objective of this study was therefore to investigate the calcium homeostasis in
      rat motoneurons under physiological stimulation of AMPA-type GluR channels using
      calcium imaging techniques and patch-clamp recordings simultaneously. It was
      found that spontaneous excitatory postsynaptic currents of cultured motoneurons
      did not elicit significant intracellular calcium transients. Large intracellular
      calcium transients occurred only when preceding fast sodium currents were
      observed. Pharmacological experiments showed that activation of AMPA-type GluR
      channels during synaptic transmission has a great functional impact on the
      calcium homeostasis in motoneurons as all kinds of activity was completely
      blocked by application of the selective kainate- and AMPA-type GluR channel
      blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Furthermore we suggest from
      our experiments that calcium transients of several hundred milliseconds' duration
      result from release of calcium from the endoplasmic reticulum via activation of
      ryanodine receptors (calcium-induced calcium release, CICR). Our results help to
      understand the regulatory function of AMPA-type GluR channels in the
      intracellular calcium homeostasis which is known to be disturbed in
      neurodegenerative diseases.

PMID- 16949761
TI  - Potential roles for hyaluronan and CD44 in kainic acid-induced mossy fiber
      sprouting in organotypic hippocampal slice cultures.
AB  - The most well-documented synaptic rearrangement associated with temporal lobe
      epilepsy is mossy fiber sprouting (MFS). MFS is a pronounced expansion of granule
      cell mossy fiber axons into the inner dentate molecular layer. The recurrent
      excitatory network formed by MFS is hypothesized to play a critical role in
      epileptogenesis, which is the transformation of the normal brain into one that is
      prone to recurrent spontaneous seizures. While many studies have focused on the
      functional consequences of MFS, relatively few have investigated the molecular
      mechanisms underlying the increased propensity of mossy fibers to invade the
      inner molecular layer. We hypothesized that changes in two components of the
      extracellular matrix, hyaluronan and its primary receptor, CD44, contribute to
      MFS. Hyaluronan contributes to laminar-specificity in the hippocampus and
      increases in hyaluronan and CD44 are associated with temporal lobe epilepsy. We
      tested our hypothesis in an in vitro model of MFS using a combination of
      histological and biochemical approaches. Application of kainic acid (KA) to
      organotypic hippocampal slice cultures induced robust MFS into the inner dentate
      molecular layer compared with vehicle-treated controls. Degradation of hyaluronan
      with hyaluronidase significantly reduced but did not eliminate KA-induced MFS,
      suggesting that hyaluronan played a permissive role in MFS, but that loss of
      hyaluronan signaling alone was not sufficient to block mossy fiber
      reorganization. Comparison of CD44 expression with MFS revealed that when CD44
      expression in the molecular layers was high, MFS was minimal and when CD44
      expression/function was reduced following KA treatment or with function blocking
      antibodies, MFS was increased. The time course of KA-induced reductions in CD44
      expression was identical to the temporal progression of KA-induced MFS reported
      previously in hippocampal slice cultures, suggesting that reduced CD44 expression
      may help promote MFS. Understanding the molecular mechanisms underlying MFS may
      lead to therapeutic interventions that limit epileptogenesis.

PMID- 16949762
TI  - Immunohistochemical analysis of acid-sensing ion channel 2 expression in rat
      dorsal root ganglion and effects of axotomy.
AB  - Several studies have suggested that acid-sensing ion channel 2 (ASIC2) plays a
      role in mechanoperception and acid sensing in the peripheral nervous system. We
      examined the expression and distribution of ASIC2 in the rat dorsal root
      ganglion, the co-localization of ASIC2 with tropomyosin-related kinase (trk)
      receptors, and the effects of axotomy on ASIC2 expression. ASIC2 immunoreactivity
      was observed in both neurons and satellite cells. ASIC2-positive neurons
      accounted for 16.5 +/- 2.4% of the total neurons in normal dorsal root ganglion.
      Most ASIC2-positive neurons were medium-to-large neurons and were labeled with
      neurofilament 200 kD (NF200). Within these neurons, ASIC2 was not evenly
      distributed throughout the cytoplasm, but rather was accumulated prominently in
      the cytoplasm adjacent to the axon hillock and axonal process. We next examined
      the co-localization of ASIC2 with trk receptors. trkA was expressed in few ASIC2
      positive neurons, and trkB and trkC were observed in 85.2% and 53.4% of ASIC2
      positive neurons, respectively, while only 6.9% of ASIC2-positive neurons were co
      localized with trkC alone. Peripheral axotomy markedly reduced ASIC2 expression
      in the axotomized dorsal root ganglion neurons. On the other hand, intense ASIC2
      staining was observed in satellite cells. These results show that ASIC2 is
      expressed in the distinct neurochemical population of sensory neurons as well as
      satellite cells, and that peripheral axotomy induced marked reductions in ASIC2
      in neurons.

PMID- 16949763
TI  - Modulation and impact of class I major histocompatibility complex by neural stem
      cell-derived neurotrophins on neuroregeneration.
AB  - Transplantation of neural stem cells (NSC) has shown to elicit functional
      recovery in experimental animal and human models of neural disorders pertaining
      to cell loss or degeneration. However, the underlying mechanisms of the regimen
      are not well understood. The scenarios lead to the speculation of
      neuroregeneration and replacement of lost neurons in both the central nervous
      system (CNS) and the peripheral nervous system (PNS). The repair per se is
      extremely complex involving the re-building and modulation of synapses, neurites,
      neural cells and glial cells. Neurotrophins, which nourish the CNS and the PNS,
      may attribute to the functional improvement after neural stem cell
      transplantation. Recent studies suggested the CNS plasticity may be modulated by
      the class I major histocompatibility complex (MHC), which are in turn regulated
      by neurotrophins. Based upon these findings, we speculate that the neurotrophins
      derived from the transplanted NSC may modulate the expression of the major
      histocompatibility complex in the injured microenvironment to facilitate
      neurological recovery. The proposition may have clues on the development of novel
      treatment modality to cure CNS injury.

PMID- 16949764
TI  - The effect of timing of radiotherapy after breast-conserving surgery in patients
      with positive or close resection margins, young age, and node-negative disease,
      with long term follow-up.
AB  - PURPOSE: The aim of this study was to determine the effect of timing of
      radiotherapy after conservative breast surgery on local recurrence in women with
      positive resection margins and young age, treated without systemic therapy.
      METHODS AND MATERIALS: A total of 568 patients with T1 and T2, N0 breast cancer
      were treated with breast-conserving surgery and breast irradiation, between
      January 1, 1985, and December 31, 1992, at the London Regional Cancer Centre. 63
      patients (11.1%) had positive/close resection margins (< 2 mm) and 48 patients
      (8.4%) were age < or = 40 years. For patients with positive resection margins,
      the time intervals from breast surgery to breast irradiation used for analysis
      were, 0 to 8 weeks, > 8 to 12 weeks and > 12 weeks. For patients < or = 40 years,
      the intervals used for analysis were 0 to 8 weeks and > 8 weeks. RESULTS: Median
      follow up was 11.2 years. For patients < or = 40 years, local recurrence rate at
      5 and 10 years was 17.2% and 19.8% respectively. Four patients (17.4%) treated in
      the 0-week to 8-week interval and 7 patients (28.0%) treated in the > 8 week
      interval had local recurrences. For patients < or = 40 years with positive
      resection margins, the local recurrence rate was 25.0%. For patients with
      positive resection margins, 5-year and 10-year local recurrence rates were as
      follows: 0 to 8 weeks, 0% and 10.5% respectively; > 8 to 12 weeks, 10.3% and
      10.3% respectively; and > 12 weeks, 13.3% and 20.0% respectively. CONCLUSION:
      Patients < or = 40 years have an increased local recurrence rate which occurs
      early. Patients with positive resection margins have higher local recurrence
      rates that become apparent when breast irradiation is delayed.

PMID- 16949765
TI  - Pitch, roll, and yaw variations in patient positioning.
AB  - PURPOSE: To use pretreatment megavoltage-computed tomography (MVCT) scans to
      evaluate positioning variations in pitch, roll, and yaw for patients treated with
      helical tomotherapy. METHODS AND MATERIALS: Twenty prostate and 15 head-and-neck
      cancer patients were selected. Pretreatment MVCT scans were performed before
      every treatment fraction and automatically registered to planning kilovoltage CT
      (KVCT) scans by bony landmarks. Image registration data were used to adjust
      patient setups before treatment. Corrections for pitch, roll, and yaw were
      recorded after bone registration, and data from fractions 1-5 and 16-20 were used
      to analyze mean rotational corrections. RESULTS: For prostate patients, the means
      and standard deviations (in degrees) for pitch, roll, and yaw corrections were 
      0.60 +/- 1.42, 0.66 +/- 1.22, and -0.33 +/- 0.83. In head-and-neck patients, the
      means and standard deviations (in degrees) were -0.24 +/- 1.19, -0.12 +/- 1.53,
      and 0.25 +/- 1.42 for pitch, roll, and yaw, respectively. No significant
      difference in rotational variations was observed between Weeks 1 and 4 of
      treatment. Head-and-neck patients had significantly smaller pitch variation, but
      significantly larger yaw variation, than prostate patients. No difference was
      found in roll corrections between the two groups. Overall, 96.6% of the
      rotational corrections were less than 4 degrees. CONCLUSIONS: The initial
      rotational setup errors for prostate and head-and-neck patients were all small in
      magnitude, statistically significant, but did not vary considerably during the
      course of radiotherapy. The data are relevant to couch hardware design for
      correcting rotational setup variations. There should be no theoretical difference
      between these data and data collected using cone beam KVCT on conventional
      linacs.

PMID- 16949766
TI  - Long-term normal-appearing brain tissue monitoring after irradiation using proton
      magnetic resonance spectroscopy in vivo: statistical analysis of a large group of
      patients.
AB  - PURPOSE: The aim of this study was to detect the non-neoplastic white-matter
      changes vs. time after irradiation using 1H nuclear magnetic resonance (NMR)
      spectroscopy in vivo. METHODS AND MATERIALS: A total of 394 1H MR spectra were
      acquired from 100 patients (age 19-74 years; mean and median age, 43 years)
      before and during 2 years after radiation therapy (the mean absorbed doses
      calculated for the averaged spectroscopy voxels are similar and close to 20 Gy).
      RESULTS: Oscillations were observed in choline-containing compounds
      (Cho)/creatine and phosphocreatine (Cr), Cho/N-acetylaspartate (NAA), and center
      of gravity (CG) of the lipid band in the range of 0.7-1.5 ppm changes over time
      reveal oscillations. The parameters have the same 8-month cycle period; however
      the CG changes precede the other by 2 months. CONCLUSIONS: The results indicate
      the oscillative nature of the brain response to irradiation, which may be caused
      by the blood-brain barrier disruption and repair processes. These oscillations
      may influence the NMR results, depending on the cycle phase in which the NMR
      measurements are performed in. The earliest manifestation of radiation injury
      detected by magnetic resonance spectroscopy is the CG shift.

PMID- 16949767
TI  - Frequency and characteristics of docetaxel-induced radiation recall phenomenon.
AB  - PURPOSE: The aim of this study was to investigate the frequency and
      characteristics of a docetaxel-induced radiation recall phenomenon. METHODS AND
      MATERIALS: Past histories of radiotherapy and radiation recall phenomenon (RRP)
      were analyzed in 461 patients who were administered docetaxel at our hospital
      between September 2002 and November 2005. RESULTS: Of the 461 patients, 171
      underwent radiotherapy before starting docetaxel. RRP was noted in 3 patients
      (1.8%). The 3 cases show that RRP tends to develop in patients treated with lower
      energy photon beams of < or =6 MV and in patients with marked acute phase
      reactions during radiotherapy. CONCLUSIONS: The incidence of RRP induced by
      docetaxel was 1.8%, making it a comparatively rare condition. However, docetaxel
      is increasingly being used for patients with head and neck tumors, and caution
      regarding development of RRP is warranted after use of docetaxel after high-dose
      radiotherapy with photon beams of < or =6 MV.

PMID- 16949768
TI  - Benefit of three-dimensional image-guided stereotactic localization in the
      hypofractionated treatment of lung cancer.
AB  - PURPOSE: The aim of this study was to investigate the benefit of image-guided
      stereotactic localization in the hypofractionated treatment for medically
      inoperable non-small-cell lung cancer. METHODS AND MATERIALS: A stereotactic body
      localizer (SBL) system was used for patient immobilization, reliable image
      registration among multiphase computed tomography (CT) scanning, and image-guided
      stereotactic localization. Three sets of CT scans were taken (free breathing, and
      breath holding at the end-tidal inspiration and expiration, respectively) to
      contrast target motion. Target delineation was performed on all 3 sets of images
      and the combination of the targets forms an internal target volume (ITV). In this
      retrospective study of treatment dose verification, we performed image fusion
      between the simulation CT scan and each pretreatment CT scan to obtain the same
      target and critical structure information. The same treatment plans were reloaded
      onto each pretreatment CT scan with their respective stereotactic coordinate
      system. The changes in dose distributions were assessed by dose-volume histograms
      of the planning target volume (PTV) and the critical structures before and after
      isocenter corrections which were prompted by image-guided stereotactic
      localization. We compared D95, D99, and V95 for the PTV and internal target
      volume, and V20 and V30 for the ipsilateral lung. RESULTS: Our retrospective
      study for 10 patients with 40 dose reconstructions showed that the average D95,
      D99, and V95 of the PTVs are 92.1%, 88.1%, and 95.8% of the planned values before
      isocenter corrections. With the corrections, all of these values are improved to
      100% of the planned values. CONCLUSIONS: Three-dimensional image guidance is
      crucial for stereotactic radiotherapy of lung tumors.

PMID- 16949769
TI  - Relationship between delay in radiotherapy and biochemical control in prostate
      cancer.
AB  - PURPOSE: The aim of this study was to investigate whether a delay in radiotherapy
      is associated with a poorer biochemical control for prostate cancer. METHODS: The
      time to treatment (TTT) from diagnosis of prostate cancer to radiotherapy was
      analyzed with respect to prostate-specific antigen (PSA) control in 1024 hormone
      naive patients. The Kaplan-Meier PSA control curves for patients with TTT less
      than the median were compared with those for patients with TTT greater than the
      median in 3 predefined risk groups. Statistical significant differences in PSA
      control were further analyzed using Cox multivariate analysis with pretreatment
      PSA, Gleason score, T stage, and radiotherapy dose as covariates. RESULTS: The
      median TTT and median follow-up are 3.7 months and 49 months respectively.
      Patients with a longer TTT have a statistically significant better PSA control
      than patients with a shorter TTT if they have intermediate- or high-risk disease.
      However in multivariate analysis TTT was not found to be significant in
      predicting PSA control, with pretreatment PSA and Gleason score emerging as
      highly significant in predicting PSA failure in both intermediate- and high-risk
      disease. CONCLUSION: In this study in prostate cancer patients in British
      Columbia, there was no evidence that a longer time interval between diagnosis and
      radiotherapy was associated with poorer PSA control.

PMID- 16949770
TI  - Treatment of penile carcinoma: to cut or not to cut?
AB  - PURPOSE: The aim of this study was to assess the outcome in patients with penile
      cancer. METHODS AND MATERIALS: A total of 60 patients with penile carcinoma were
      included. Of the patients, 45 (n = 27) underwent surgery, and 51 underwent
      definitive (n = 29) or postoperative (n = 22) radiotherapy (RT). Median follow-up
      was 62 months. RESULTS: Median time to locoregional relapse was 14 months. Local
      failure was observed in 3 of 23 patients (13%) treated with surgery with or
      without postoperative RT vs. in 19 of 33 patients (56%) given organ-sparing
      treatment (p = 0.0008). Of 22 local failures, 16 (73%) were salvaged with
      surgery. Of the 33 patients treated with definitive RT (n = 29) and the 4
      patients refusing RT after excisional biopsy, local control was obtained with
      organ preservation in 13 (39%). In the remaining 20, 4 patients with local
      failure underwent salvage conservatively, resulting in an ultimate penis
      preservation rate of 17 of 33 (52%) patients treated with definitive RT. The 5
      year and 10-year probability of surviving with an intact penis was 43% and 26%,
      respectively. There was no survival difference between the patients treated with
      definitive RT and primary surgery (56% vs. 53%; p = 0.16). In multivariate
      analysis, independent factors influencing survival were N-classification and
      pathologic grade. Surgery was the only independent predictor for better local
      control. CONCLUSION: Based on our study findings, in patients with penile cancer,
      local control is superior with surgery. However, there is no difference in
      survival between patients treated with surgery and those treated with definitive
      RT, with 52% organ preservation.

PMID- 16949771
TI  - Origin and evolution of gene for prolactin-induced protein.
AB  - Prolactin-induced protein (PIP) is a small protein secreted into the fluid in
      several glands. We determined the PIP coding sequences of 5 hominoid species and
      estimated the numbers of synonymous and nonsynonymous substitutions for each
      branch of the mammalian PIP gene tree. The branch connecting hominoids and Old
      World monkeys showed significantly higher nonsynonymous than synonymous
      substitutions. These changes tended to be accumulated in the fibronectin-binding
      domain. Many other primate branches also showed higher nonsynonymous than
      synonymous substitutions, thus suggesting that the PIP genes of primates have
      experienced some kind of positive selection. We also considered the phylogenetic
      relationship of the PIP gene with the alpha-2-macroglobulin gene family. The
      results indicate that the PIP gene arose by partial gene duplication from a
      member of the alpha-2-macroglobulin gene family after the divergence between
      amphibians and other tetrapods.

PMID- 16949772
TI  - How genomes rearrange: genome comparison within bacteria Neisseria suggests roles
      for mobile elements in formation of complex genome polymorphisms.
AB  - Comparison of closely related genome sequences can provide a clue as to how
      macroscopic genome polymorphisms were formed through various events of
      recombination. However, this approach has been limited to relatively simple
      polymorphisms such as insertion, deletion and inversion. In the present study, we
      tried to extend this approach to more complex genome polymorphisms that were
      observed when four genome sequences of bacterial genus Neisseria were compared.
      The first polymorphism was an apparent translocation (ab-cd to cd-ba; a region
      'ab' was translocated). The second one was a re-ordering of adjacent regions (ab
      cd-ef-gh to ef-cd-ab-gh; ab, cd and ef were in reverse order). The third one was
      a translocation of two adjacent regions with permutation of their order (ab-cd to
      cd-ab elsewhere in the genome). The fourth one was a genome-wide inversion
      associated with a genome-specific insertion into the joints (-ab-cd- to -y-ba-x
      cd-). We were able to explain their formation by only a few steps of plausible
      events of recombination that involved linked IS copies and prophages. Our
      approach would help to reconstruct a history of apparently complex genome
      polymorphisms in any forms of organisms and to understand genome rearrangements
      in the natural environments in non-model organisms.

PMID- 16949773
TI  - Using BiliCheck for preterm neonates in a sub-intensive unit: diagnostic
      usefulness and suitability.
AB  - BACKGROUND: BiliCheck (BC), a new transcutaneous bilirubinometer is thought to be
      lacking in the disadvantages of old devices and could be potentially useful for
      diagnosing jaundice in preterm babies. Although its accuracy is well known in
      healthy term babies, there is a lack of knowledge about its usefulness in preterm
      infants. AIMS: To investigate BC usefulness in preterm babies and its suitability
      in a sub-intensive neonatal unit. STUDY DESIGN: In 340 preterm infants between 30
      and 36 weeks of gestational age, transcutaneous and serum bilirubin measurement
      were performed. Hematocrit, pH, postnatal age, gestational age, and sex were also
      studied to clarify their influence on BC accuracy. For a subset of 100 neonates
      transcutaneous measurement, blood collection and serum analysis were timed and
      costs were considered. RESULTS: Correlation coefficient is 0.795 (p<0.001) and
      this is not affected by factors previously supposed to be important. Overall
      sensitivity was 100% and specificity were comprised between 40% and 72%. BC has a
      tendency to overestimate serum bilirubin, at high values. Considering the whole
      time for serum bilirubin measurement, transcutaneous bilirubinometry is a faster
      (p<0.0001), but more expensive technique with a cost of about 5 euro/measurement.
      Nevertheless, using BC as a screening-device we could safely avoid 58-79% of
      blood samples, since its positive predictive values is about 21-42%. This would
      allow to a cost reduction of 1555-2120 euro/year. CONCLUSIONS: BC has a good
      reliability in preterm infants although not as good as in healthy term babies. BC
      is a time-sparing tool and can improve the management of neonatal jaundice in
      preterm infants; however, its tendency to overestimate suggests its use only for
      screening purposes.

PMID- 16949774
TI  - Advances in hormone replacement therapy with drospirenone, a unique progestogen
      with aldosterone receptor antagonism.
AB  - Unlike other currently available progestogens, drospirenone (DRSP) has a
      pharmacological profile, which closely mimics that of endogenous progesterone,
      most notably potent anti-aldosterone and anti-androgenic effects. Consequently,
      DRSP, when combined with 17beta-estradiol (E2) as hormone replacement therapy
      (HRT), offsets E2-related water and sodium retention by blocking the
      mineralocorticoid receptor. This review evaluates the potential benefits offered
      by DRSP as the progestin component of HRT with respect to its anti-aldosterone
      activity, which translates into positive effects on body weight and blood
      pressure in clinical trials of continuous, combined E2/DRSP in post-menopausal
      women. In a 1-year, large-scale, randomised, controlled trial, E2 1 mg/DRSP 2 mg
      significantly decreased mean body weight by 1.2 kg versus baseline (P<0.001),
      whereas patients receiving E2 1 mg gained weight. E2 1 mg/DRSP 2 mg also
      significantly lowered mean systolic blood pressure (SBP) by 9.0 mmHg from
      baseline (P<0.05) versus 3.7 mmHg in the E2 1 mg group (P=0.220) in a sub-group
      of hypertensive women. In addition, E2/DRSP was not associated with hyperkalaemia
      (potassium > or =5.5 meq/L) irrespective of concomitant use of ACE inhibitors,
      angiotensin II receptor antagonists or non-steroidal anti-inflammatory drugs, and
      co-morbid diabetes mellitus. In summary, as well as effectively treating
      climacteric symptoms, DRSP 2 mg combined with E2 1 mg has shown positive effects
      on body weight and blood pressure in clinical trials, most likely due to DRSP's
      anti-aldosterone properties. This combination may therefore offer an alternative
      therapeutic option with additional benefits beyond current HRT agents for
      symptomatic post-menopausal women.

PMID- 16949775
TI  - Preparation and in vitro and in vivo characterization of composite microcapsules
      for cell encapsulation.
AB  - Cell encapsulation technology raises great hopes in medicine and biotechnology.
      Transplantation of encapsulated pancreatic islets represents a promising approach
      to the final cure of type 1 diabetes mellitus. Unfortunately, long-term graft
      survival and functional competence remain only partially fulfilled. Failure was
      often ascribed to the lack of biocompatibility generating inflammatory response,
      limited immunobarrier competence, hypoxia, and low beta-cell replication. In the
      present work, ketoprofen loaded biodegradable microspheres, embedded into
      alginate/poly-L-ornithine/alginate microcapsules, were prepared in order to
      release ketoprofen at early stages after implantation. Morphology, size, in vitro
      release behaviour, and in vivo biocompatibility were assessed. The effect of some
      preparation parameters was also evaluated. Polymeric microspheres were spherical
      and smooth, two populations of about 5 and 20 microm of mean diameter
      characterized the particle size distribution. A high burst effect was observed
      for all preparations during in vitro release studies. Ketoprofen, plasticizing
      the polymeric matrix, could be responsible of this release behaviour.
      Alginate/poly-L-ornithine/alginate microcapsules were not modified upon
      ketoprofen loaded microspheres encapsulation and an optimal dispersion was
      obtained. Composite system showed good biocompatibility when a high molecular
      weight polymer was employed. Therefore a potentially suitable composite system
      for cell encapsulation was obtained. This system may be successfully used to
      release NSAIDs and other active molecules capable to improve cell system
      functional performance and life-span.

PMID- 16949776
TI  - Investigation into the potential of low-frequency ultrasound facilitated topical
      delivery of Cyclosporin A.
AB  - The potential for low-frequency ultrasound facilitated topical transport of
      Cyclosporin A was investigated using rat skin. Studies of intensity and exposure
      time acting on the deposition of Cyclosporin A into deeper skin of in vitro
      sonophoresis were performed. Low-frequency ultrasound increased the amount of
      Cyclosporin A retained in the skin only seven times than the passive diffusion.
      Furthermore, we also tested the synergistic effect of ultrasound and other
      approaches such as chemical enhancers and electroporation on topical drug
      delivery of Cyclosporin A. We found that the efficacy of low-frequency ultrasound
      in enhancing topical delivery could be further increased by pretreatment of skin
      with chemical enhancers, such as laurocapram (Azone) and sodium lauryl sulfate
      (SLS). Meanwhile only a small amount was seen to across the full skin into the
      receiver compartment. Trimodality treatment comprising of pretreatment with
      Azone+ultrasound in combination followed by electroporation was not effective in
      enhancing the topical delivery of Cyclosporin A. However, this combination
      strategy increased the penetration of Cyclosporin A through rat skin by order of
      15. The histopathological findings revealed that there was almost no change
      observed in the structure of skin after ultrasound or combination with ultrasound
      and enhancers as compared with the control group. In general, the enhanced skin
      accumulation of Cyclosporin A by the combination of low-frequency ultrasound and
      chemical enhancers could help significantly to optimize the targeting of the drug
      without of a concomitant increase of the systemic side effects.

PMID- 16949777
TI  - Exploring the potential of N-methyl pyrrolidone as a cosurfactant in the
      microemulsion systems.
AB  - The effect of N-methyl pyrrolidone (NMP) on the phase behavior of two ternary
      systems, viz. PEG-35-castor oil (CremophoreEL)-glyceryl caprylate/caprate (Capmul
      MCM)-water and PEG-35-castor oil (CremophoreEL)-isopropyl myristate-water was
      studied. The study indicated that NMP has considerable influence on the phase
      behavior of both the systems. NMP increased the area of microemulsion formation
      in both the systems. Moreover, it also led to reduction/disappearance in the
      gelling region of the CremophoreEL-isopropyl myristate-water system. These
      observations allowed us to conclude that NMP can be considered as a cosurfactant
      for the development of biocompatible microemulsions.

PMID- 16949778
TI  - Antinociceptive and anti-inflammatory effects of Thespesia populnea bark extract.
AB  - The ethanolic extract of Thespesia populnea bark (TPE) was investigated for anti
      inflammatory and analgesic activity at the doses (p.o.) of 100, 200 and 400mg/kg
      body weight. For evaluation of inflammation carrageenan-, histamine- and
      serotonin-induced paw edema served as acute models and formaldehyde-induced
      arthritis served as a chronic model in rats. The acetic acid-induced writhing
      response and formalin-induced paw licking time in the early and late phases of
      mice were used to assess analgesic activity. The higher doses of TPE (200 and
      400mg/kg, p.o.) were inhibiting carrageenan, histamine and serotonin-induced paw
      edema as well as formaldehyde-induced arthritis successfully. In addition, TPE
      (200 and 400mg/kg, p.o.) significantly attenuated the writhing responses induced
      by an intraperitoneal injection of acetic acid and late phase of pain response
      induced by an subplantar injection of formalin in mice. Furthermore, our
      phytochemical studies indicated that the ethanolic extract of bark contains
      alkaloids, carbohydrates, protein, tannins, phenols, flavonoids, gums and
      mucilage, saponins and terpenes. From acute oral toxicity studies (OECD-423
      guidelines), no mortality was observed even at highest dose of TPE (2000mg/kg,
      p.o.).

PMID- 16949779
TI  - Protective effect of the Chinese prescription Kangen-karyu against high glucose
      induced oxidative stress in LLC-PK1 cells.
AB  - We investigated the effects of Chinese prescription Kangen-karyu on high glucose
      induced oxidative stress using LLC-PK(1) cells, renal tubular cells, which are
      the most vulnerable renal tissue to oxidative stress. High-concentration glucose
      (30mM) treatment induced LLC-PK(1) cell death, but Kangen-karyu, at a
      concentration of 5, 10 or 50 microg/ml, significantly inhibited high glucose
      induced cytotoxicity. In addition, the intracellular reactive oxygen species
      level was increased by 30mM glucose treatment, but it was concentration
      dependently inhibited by Kangen-karyu treatment. Moreover, 30mM glucose treatment
      induced high levels of superoxide anion, nitric oxide and peroxynitrite. However,
      Kangen-karyu treatment significantly reduced the radical overproduction induced
      by high glucose, suggesting Kangen-karyu has radical-scavenging activity that
      would protect against oxidative stress induced by high glucose. Kangen-karyu also
      reduced the overexpression of inducible nitric oxide synthase and cyclooxygenase
      2 proteins induced by high glucose. Furthermore, treatment with Kangen-karyu, at
      a concentration of 50mug/ml, inhibited the nuclear translocation of nuclear
      factor-kappa B induced by 30mM glucose in LLC-PK(1) cells. These findings
      indicate that Kangen-karyu is a potential therapeutic agent that will reduce the
      damage caused by hyperglycemia-induced oxidative stress associated with diabetes.

PMID- 16949780
TI  - A case of nasopharyngeal actinomycosis leading to otitis media with effusion.
AB  - Nasopharyngeal actinomycosis is extremely rare, and to our knowledge, only seven
      cases have previously been reported. Diagnosis of actinomycosis is made by
      clinical finding, observation of the bacteria and histopathological examination.
      Treatment for actinomycosis is surgical debridement and administration of
      antibioticus, especially penicillin for several weeks with good prognosis. We
      report a case of nasopharyngeal actinomycosis, which lead to otitis media with
      effusion. Endoscopic surgery and prolonged penicillin administration for 2 months
      were effective for treatment of actinomycosis in the nasopharynx.

PMID- 16949781
TI  - [Malaria vaccines: prospects and reality].
AB  - The development of a malaria vaccine has been accelerating in the last ten years.
      The number of clinical trials has increased and some malaria antigens have been
      tested in endemic areas. No potential vaccine has yet shown sufficient and
      lasting efficacy to justify its inclusion in a public health program. However,
      trials have unambiguously shown that some level of anti-malaria clinical immunity
      can be achieved by vaccination, both in experimental and in field conditions.
      Advances in malaria vaccine development are presented.

PMID- 16949782
TI  - Is GastroPanel serum assay useful in the diagnosis of Helicobacter pylori
      infection and associated gastritis in children?
AB  - GastroPanel (Biohit, Helsinki, Finland) is a serum test kit that measures
      Helicobacter pylori antibodies (HPABs) and pepsinogens I and II and gastrin 17,
      which reflect the degree of atrophic gastritis. We assessed whether GastroPanel
      can replace endoscopic biopsies in the diagnostics of H. pylori in children and
      whether the H. pylori-infected children show markers for atrophic gastritis.
      Eighty children (median age, 6.8 years; range, 0.6-18.7 years) underwent
      gastroscopy for H. pylori-related abdominal complaints (n = 40), surveillance
      after surgery for gastrointestinal tract malformations (n = 20), gastroesophageal
      reflux (GER) (n = 10), and miscellaneous diseases (n = 10). Gastric biopsies and
      a serum sample were obtained from all 80 children. HPAB levels of 38 and 15 IU
      were tested as cutoff values for H. pylori gastritis. The biopsies showed H.
      pylori-positive gastritis in 30 children, 9 had gastritis not associated with H.
      pylori, and 41 had normal biopsies. Atrophic gastritis was not found. The
      sensitivity and specificity of HPAB for H. pylori were 47% and 98% (cutoff, 38
      IU), and 73% and 85% (cutoff, 15 IU), respectively. The assays of pepsinogens and
      gastrin did not improve sensitivity. None of the markers of pepsinogen (PG) I,
      PGII, and gastrin 17 (G17) indicated atrophic gastritis. GastroPanel is too
      insensitive for H. pylori screening and does not replace endoscopy. Markers
      indicative of atrophic gastritis were negative in all children with H. pylori
      gastritis.

PMID- 16949783
TI  - In vitro activities of ertapenem against drug-resistant Streptococcus pneumoniae
      and other respiratory pathogens from 12 Asian countries.
AB  - In vitro activities of ertapenem and 11 other comparator agents were tested
      against 1025 isolates of respiratory pathogens collected from 12 Asian countries.
      Resistance rate to ertapenem was 1.2% in 602 isolates of Streptococcus pneumoniae
      (MIC(50), 0.06/MIC(90), 1 microg/mL). Ertapenem was also very active against
      penicillin-, ciprofloxacin-, erythromycin-, and multidrug-resistant pneumococcal
      isolates (resistance rate: 3.5%, 2.7%, 1.9%, and 2.7%, respectively). Ertapenem
      resistant pneumococcal isolates were found only in Vietnam and Korea. Ertapenem
      resistance was not found in methicillin-susceptible Staphylococcus aureus,
      Haemophilus influenzae, Moraxella catarrhalis, and Klebsiella pneumoniae,
      including extended-spectrum beta-lactamase producers. In vitro data suggest that
      ertapenem could be a useful treatment option for community-acquired pneumonia.

PMID- 16949784
TI  - Development and evaluation of a 4-target multiplex real-time polymerase chain
      reaction assay for the detection and characterization of Yersinia pestis.
AB  - A multiplexed, 4-target real-time polymerase chain reaction (PCR) assay for the
      detection and characterization of Yersinia pestis was designed and optimized for
      respiratory and environmental samples. The target sequences include the entF3
      gene of the chromosome, pla (plasminogen activator) on the pPCP1 virulence
      plasmid, caf1 (F1 capsule antigen) on the pMT1 virulence plasmid, and a region
      located on the pCD1 plasmid. The sensitivity of this assay was determined to be
      less than 85 CFU per reaction for each specimen type analyzed. This assay was
      also determined to be 100% specific with strains of Y. pestis, 9 additional
      Yersinia species, and related enteric and respiratory organisms. The results show
      that this multiplex real-time PCR assay using TaqMan(R) (Roche Molecular Systems,
      Inc., Alameda, CA) chemistry is sensitive and specific, requires minimal sample
      input, and can yield results in approximately 4 h. This assay is the first 4
      target multiplex real-time PCR assay for Y. pestis in which detection and
      virulence assessment of Y. pestis can occur in one reaction, from clinical and
      environmental samples.

PMID- 16949785
TI  - Use of the infra hyoid musculo-cutaneous flap in soft palate reconstruction.
AB  - AIMS: To review a series of 23 consecutive patients with squamous cell carcinomas
      arising from oropharynx who underwent infra hyoid musculo-cutaneous flap
      reconstruction including soft palate in alternative to free radial forearm flap
      or maxillofacial prosthesis. Post operative radiotherapy was performed for all
      patients. RESULTS: Every reconstruction healed quickly without major wound
      complications. The functional results evaluated by speech and swallowing
      capacities, were good for 17 patients, fair for 4 patients and bad for 2.
      CONCLUSIONS: The infra hyoid musculo-cutaneous flap is a versatile, reliable and
      convenient flap suitable for repairing small and medium sized defects; it can be
      used in combination with other flaps, and in selected cases obviates the need for
      a microvascular free radial forearm flap or maxillofacial prosthesis.

PMID- 16949786
TI  - Post-translational modifications of steroid receptors.
AB  - The multiple physiological functions of steroid hormones have been known for many
      years. The cloning of the steroid receptors in the mid-1980s led to the concept
      of ligand-activated transcription factors and to the identification of specific
      DNA response elements in the regulatory regions of target genes. The next main
      development was the identification of cofactors with activating or repressing
      functions, of which several act by modifying histones and locally affecting the
      chromatin structure. Work from several groups shows that the steroid receptors
      themselves can also be modified at various positions. Besides the long-known
      phosphorylation at tyrosines and serine/threonine residues, other covalent
      additions such as acetylation, ubiquitylation and sumoylation have been evidenced
      for steroid receptors in recent years. These modifications affect receptor
      stability and activity, and provide potential mechanisms for cell- or gene
      specific regulation. A better understanding of the impact of these post
      translational modifications (PTMs) on steroid receptor function should help in
      the identification of novel ligands with improved clinical profiles.

PMID- 16949787
TI  - Protein tyrosine kinase signaling diversity and susceptibility to targeted kinase
      inhibitors.
AB  - Protein kinases, including tyrosine kinases, are one of the largest classes of
      proteins implicated in cancer development and progression. Recent discovery of
      selective therapies targeting tyrosine kinase receptor signaling has provided
      encouraging clinical results. Clinical trials with anti-EGFR, anti-ErbB2/Her2,
      anti-Bcr-Abl and others have demonstrated the clinical utility of tyrosine
      kinases as therapeutic targets and as surrogate markers to guide the selection of
      patients susceptible to respond to treatment. This success has been tempered in
      part because resistance to targeted therapies is now documented to occur in
      experimental models and in patients, which hampers therapeutic efficacy.
      Mechanisms of resistance include cell heterogeneity in target expression,
      mutations in target's encoding genes, and compensatory signaling mechanisms. This
      paper provides a brief overview on the diversity of tyrosine kinase signaling and
      the impact on cancer cell response to targeted tyrosine kinase inhibitors.

PMID- 16949788
TI  - Focal adhesion kinase is involved in type III group B streptococcal invasion of
      human brain microvascular endothelial cells.
AB  - Group B streptococcus (GBS), the leading cause of neonatal meningitis, has been
      shown to invade human brain microvascular endothelial cells (HBMEC), which
      constitute the blood-brain barrier. GBS invasion of HBMEC has been shown to
      require the host cell actin cytoskeleton rearrangements. The present study
      examined the mechanisms underlying actin cytoskeleton rearrangements that are
      involved in type III GBS invasion of HBMEC. We showed that type III GBS invasion
      was inhibited by genistein, a general tyrosine kinase inhibitor (mean 54%
      invasion decrease at 100 microM), and LY294002, a phosphatidylinositol 3 (PI3)
      kinase inhibitor (mean 70% invasion decrease at 50 microM), but not by PP2, an
      inhibitor of the Src family tyrosine kinases. We subsequently showed that the
      focal adhesion kinase (FAK) was the one of the host proteins tyrosine
      phosphorylated by type III GBS. Over-expression of a dominant negative form of
      the FAK C-terminal domain significantly decreased type III GBS invasion of HBMEC
      (mean 51% invasion decrease). In addition, we showed that FAK phosphorylation
      correlated with its association of paxillin, an adapter protein of actin
      filament, and PI3-kinase subunit p85. This is the first demonstration that FAK
      phosphorylation and its association with paxillin and PI3 kinase play a key role
      in type III GBS invasion of HBMEC.

PMID- 16949789
TI  - Restraint stress facilitates systemic dissemination of Theiler's virus and alters
      its pathogenecity.
AB  - Theiler's murine encephalomyelitis virus (TMEV), a Picornavirus used as a viral
      model for multiple sclerosis (MS), causes an acute encephalomyelitis and chronic
      demyelination. The failure to clear the virus, which can result from stress, is a
      prerequisite for development of the later disease. Similarly, stressful life
      events have been associated with the development of MS. In the present study, a
      restraint stress (RS) model was used to investigate the effect of stress on the
      systemic dissemination of TMEV during the early stage of disease. Experimental
      data demonstrated that repeated RS remarkably facilitated the spread of virus
      from the CNS to such systemic organs as the spleen, lymph nodes, thymus, lungs
      and heart and compromised the ability of viral clearance within those tissues. RS
      also altered the pathogenecity of TMEV, enabling it to become cardiotropic,
      resulting in higher myocardial infectivity. These results demonstrate the
      profound impact that RS has upon both the tissue and organ dissemination of the
      virus, and the organ tropism of TMEV. An additional finding associated with
      stress was hepatic necrosis in the restrained animals, regardless of whether or
      not they were infected.

PMID- 16949790
TI  - In vitro genotoxicity and cytotoxicity of benzalkonium chloride.
AB  - Benzalkonium chloride (BAC) acts as a preservative in numerous nasal
      preparations. Possible genotoxic and cytotoxic effects of BAC in human
      respiratory epithelial BEAS-2B cells should be investigated in vitro. Cell
      cultures were exposed for 2h to BAC in concentrations ranging from 0.002% to
      0.05%. Methyl methanesulfonate served as positive control, PBS as negative
      control. The tail moment of single-cell gel-electrophoresis (SCGE) was used to
      assess BAC-induced DNA damage. Cell viability was measured by trypan blue dye
      exclusion staining. Additionally, the critical micellar concentration (CMC) of
      BAC in PBS was detected. The tail moment increased dose dependently with the
      maximum value at 0.02%, and declined for higher concentrations. Nearly all cells
      died at low BAC concentrations up to 0.01%. Above this concentration cell
      viability increased. The CMC of BAC in PBS was estimated to be 0.02%. BAC caused
      relevant DNA changes in respiratory epithelial cells in vitro at concentrations
      commonly employed in commercially available nasal preparations. Some of the
      exposed cells survived. In further studies it could be considered to look whether
      these cells would still be able to proliferate and possibly fix the damage that
      they have possibly accumulated into an actual mutation using for example the
      induction of micronuclei.

PMID- 16949791
TI  - X chromosome gene expression in human tissues: male and female comparisons.
AB  - About 25% of X-linked genes may escape inactivation at least to some degree.
      However, in vitro results from somatic cell hybrids may not reflect what happens
      in vivo. Therefore, we analyzed the female/male (F/M) gene fold expression ratio
      for 299 X-linked and 7795 autosomal genes from 11 different tissues from an
      existing in vivo microarray database. On average 5.1 and 4.9% of genes showed
      higher expression in females compared with 7.4 and 7.9% in males, respectively,
      for X-linked and autosomal genes. A trend was found for F/M gene fold ratios
      greater than 1.5 for several X-linked genes indicating overexpression in females
      among multiple tissues. Nine X-linked genes showed overexpression in females in
      at least 3 of the 11 studied tissues. Of the 9 genes, 6 were located on the short
      arm and 3 on the long arm of the X chromosome. Six of the 9 genes have previously
      been reported to escape X inactivation. However, in general, no consistent
      pattern was seen for the expression of X-linked genes between in vitro and in
      vivo systems. This study indicates that factors other than the X-inactivation
      process may impact on the expression of X-linked genes resulting in an overall
      similar gender expression for both X-linked and autosomal genes.

PMID- 16949792
TI  - The role of short-term depression in sustained neural activity in the prefrontal
      cortex: a simulation study.
AB  - Recent experimental researches have suggested that sustained neural activity in
      the prefrontal cortex is a process of memory retention in decision making.
      Previous theoretical studies indicate that a balance between recurrent excitation
      and feedback inhibition is important for sustaining the activity. To investigate
      a plausible balancing mechanism, we simulated a biophysically realistic network
      model. Our model shows that short-term depression (STD) enables the network to
      sustain its activity despite the presence of long-term inhibition by GABA(B)
      receptors and that the sustained firing rates have a bell-shaped dependence on
      the degree of STD. By analyzing the neural network dynamics, we show that the
      bell-shaped dependence on STD is formed by destabilizing the balance with either
      excessive or insufficient STD. We also show that the optimal degree of STD has a
      linear relationship with the neural network size. These results suggest that STD
      provides a balancing mechanism and controls levels of sustained activities of
      various size networks.

PMID- 16949793
TI  - Image formation in vibro-acoustography with depth-of-field effects.
AB  - We study the image formation of vibro-acoustography systems based on a concave
      sector array transducer taking into account depth-of-field effects. The system
      point-spread function (PSF) is defined in terms of the acoustic emission of a
      point-target in response to the dynamic radiation stress of ultrasound. The PSF
      on the focal plane and the axis of the transducer are presented. To extend the
      obtained PSF to the 3D-space, we assume it is a separable function in the axial
      direction and the focal plane of the transducer. In this model, an image is
      formed through the 3D convolution of the PSF with an object function.
      Experimental vibro-acoustography images of a breast phantom with lesion-like
      inclusions were compared with simulated images. Results show that the
      experimental images are in good agreement with the proposed model.

PMID- 16949794
TI  - Differential G-alpha interaction capacities of the GoLoco motifs in Rap GTPase
      activating proteins.
AB  - GoLoco motif proteins act as guanine nucleotide dissociation inhibitors (GDIs)
      for G-protein alpha subunits of the adenylyl cyclase-inhibitory (Galpha(i/o))
      class. Rap1GAP2 is a newly identified GoLoco motif- and RapGAP domain-containing
      protein, and thus is considered a potential integrator of heterotrimeric and
      monomeric GTPase signaling. Primary sequence analysis indicated that the Rap1GAP2
      GoLoco motif contains a lysine (Lys-75), rather than an arginine, at the crucial
      residue responsible for binding the alpha and beta phosphates of GDP and exerting
      GDI activity. To determine the functional outcome of this sequence variation we
      conducted a biophysical analysis of the human Rap1GAP2b/c GoLoco motif. We found
      that human Rap1GAP2b/c was deficient in GDI activity and Galpha interaction
      capability. Mutation of lysine-75 to arginine could not regain functional
      activity of the Rap1GAP2b/c GoLoco motif. Thus, the Rap1GAP2b/c GoLoco motif can
      be classed as inactive towards Galpha subunits. We also found that the Rap1GAP1a
      GoLoco motif, which lacks seven N-terminal amino acid residues present in
      canonical GoLoco motifs, does not interact with Galpha(i1). In contrast, the
      GoLoco motif of Rap1GAP1b, which is canonical in primary sequence, was found to
      interact with Galpha(i1).GDP.

PMID- 16949795
TI  - Androgen dependent regulation of protein kinase A subunits in prostate cancer
      cells.
AB  - Neuroendocrine (NE) cells may play a role in prostate cancer progression. Both
      androgen deprivation and cAMP are well known inducers of NE differentiation (NED)
      in the prostate. Gene-expression profiling of LNCaP cells, incubated in androgen
      stripped medium, showed that the Cbeta isoform of PKA is up-regulated during NE
      differentiation. Furthermore, by using semi-quantitative RT-PCR and
      immunoblotting analysis, we observed that the Cbeta splice variants are
      differentially regulated during this process. Whereas the Cbeta2 splice variant
      is down-regulated in growth arrested LNCaP cells, the Cbeta1, Cbeta3 and Cbeta4
      variants, as well as the RIIbeta subunit of PKA, are induced in NE-like LNCaP
      cells. The opposite effect of Cbeta expression could be mimicked by androgen
      stimulation, implying the Cbeta gene of PKA as a putative new target gene for the
      androgen receptor in prostate cancer. Moreover, to investigate expression of PKA
      subunits during prostate cancer progression, we did immunoblotting of several
      prostatic cell lines and normal and tumor tissue from prostate cancer patients.
      Interestingly, multiple Cbeta subunits were also observed in human prostate
      specimens, and the Cbeta2 variant was up-regulated in tumor cells. In conclusion,
      it seems that the Cbeta isoforms play different roles in proliferation and
      differentiation and could therefore be potential markers for prostate cancer
      progression.

PMID- 16949796
TI  - Subjective and behavioural consequences of striatal dopamine depletion in
      schizophrenia--findings from an in vivo SPECT study.
AB  - Dysphoria is an integral part of the symptomatology of a variety of clinical
      states, though there is little empirical data available on the qualitative and
      quantitative aspects of this phenomenon. The purpose of the study was to
      administer alphamethyl paratyrosine (AMPT), a catecholamine depleting agent as a
      chemical probe to induce dysphoria, and document the ensuing changes in mental
      status. AMPT (4-5 g/day) was administered to a group of medication-free
      schizophrenic patients (n=13) over a 48 hour period, and changes in their mental
      status were monitored at 12 hour intervals with the Profile of Mood States
      (POMS), Addiction Research Center Inventory (ARCI), Drug Attitude Inventory (DAI)
      and other standardized rating scales. All of the subjects experienced dysphoric
      responses of variable severity. The profile of changes included blunted pleasure
      responsivity, clouded thinking, loss of motivation and lowered vigilance. Subtle
      subjective changes were experienced soon after the first dose of AMPT and the
      dysphoria steadily worsened, resulting in social withdrawal and personal
      distress. Subjective responses were the earliest to manifest, followed by
      akathisia, akinesia and rigidity. We conclude that AMPT induced dopamine
      depletion is a safe, rapid, reliable and reversible method of studying dysphoric
      states in humans. The technique is helpful in examining the phenomenology of
      dysphoria, the temporal relationship between subjective and behavioural
      consequences of dopamine depletion, and the role of dopamine in mediating subtle
      aspects of pleasure responsivity, which is in turn crucial to the understanding
      of treatment non-adherence in schizophrenia and the origins of comorbid substance
      abuse.

PMID- 16949797
TI  - Reduction of XNkx2-10 expression leads to anterior defects and malformation of
      the embryonic heart.
AB  - Normal vertebrate heart development depends upon the expression of homeodomain
      containing proteins related to the Drosophila gene, tinman. In Xenopus laevis,
      three such genes have been identified in regions that will eventually give rise
      to the heart, XNkx2-3, XNkx2-5 and XNkx2-10. Although the expression domains of
      all three overlap in early development, distinctive differences have been noted.
      By the time the heart tube forms, there is little XNkx2-10 mRNA detected by in
      situ analysis in the embryonic heart while both XNkx2-3 and XNkx2-5 are clearly
      present. In addition, unlike XNkx2-3 and XNkx2-5, injection of XNkx2-10 mRNA does
      not increase the size of the embryonic heart. We have reexamined the expression
      and potential role of XNkx2-10 in development via oligonucleotide-mediated
      reduction of XNkx2-10 protein expression. We find that a decrease in XNkx2-10
      leads to a broad spectrum of developmental abnormalities including a reduction in
      heart size. We conclude that XNkx2-10, like XNkx2-3 and XNkx2-5, is necessary for
      normal Xenopus heart development.

PMID- 16949798
TI  - A role for GATA factors in Xenopus gastrulation movements.
AB  - Gastrulation movements in Xenopus laevis are becoming increasingly well
      characterised, however the molecular mechanisms involved are less clear. Active
      migration of the leading edge mesendoderm across the fibronectin-coated
      blastocoel roof is necessary for further development of tissues such as head
      mesoderm, heart, blood and liver. The zinc finger transcription factors GATA4 and
      GATA6 are expressed in this migratory tissue during gastrulation, but their role
      here is unknown. This study further characterises the expression of GATA4 and 6
      during gastrulation, and investigates their function in migratory behaviour. Gain
      of-function experiments with these GATA factors induce cell spreading,
      polarisation and migration in non-motile presumptive ectoderm cells. Expression
      of a dominant-interfering form of GATA6, which inhibits transactivation of GATA
      targets, severely impairs the ability of dorsal leading edge mesendoderm to
      spread and translocate on fibronectin. Mosaic inhibition of GATA activity
      indicates that GATA factors function cell autonomously to induce cell spreading
      and movement in dorsal mesendoderm. Knockdown of specific GATA factors using anti
      sense morpholinos indicates that GATA4 and GATA6 both contribute to dorsal
      mesendoderm migration in vitro. GATA4 and GATA6 are known to be involved in cell
      specification of mesoderm and endoderm-derived tissues, but this is the first
      description of an additional role for these factors in cell migration.

PMID- 16949799
TI  - A pilot study of facial, cranial and brain MRI morphometry in men with
      schizophrenia: part 2.
AB  - This pilot study applies a new 3D morphometric MR method to test the hypothesis
      that men with schizophrenia (vs. controls) have deviant facial shapes and
      landmark relations in cranio/facial/brain (CFB) regions. This constitutes Part 2
      of paired articles in this issue of Psychiatry Research: Neuroimaging, in which
      Part 1 presents the new method in detail. MRI coordinates from CFB landmarks of
      23 patients and 15 controls were identified and then aligned with the Procrustes
      model, leaving shape as the only unit-less geometrical information. Men with
      schizophrenia had significantly longer mid- and lower-facial heights, and greater
      lower (left) facial depth, with a tendency toward rotation along the facial
      midline. This supports findings from earlier anthropometric and 3D studies of the
      "exterior" (face). In contrast, none of the patient-control differences for the
      new "interior" (cranial-brain) distances reached statistical significance. These
      results need to be retested on a larger sample of both sexes.

PMID- 16949800
TI  - Evaluating brain activity in obsessive-compulsive disorder: preliminary insights
      from a multivariate analysis.
AB  - Obsessive-compulsive disorder (OCD) has been linked to a dysfunction of brain
      corticostriatal networks, although functional imaging studies of OCD rarely apply
      network-sensitive analysis methods. In this study, we compared a univariate and a
      multivariate analysis of PET data in OCD patients and healthy subjects; the
      latter approach was considered more suitable for characterizing functional
      networks of brain activity. Although both methods suggested there was abnormal
      corticostriatal activity in OCD patients, the nature, extent and magnitude of
      this activity was clearly enhanced by the multivariate approach. Implications for
      the analysis of such studies are discussed.

PMID- 16949801
TI  - Investigation on water consumption characteristics and water use efficiency of
      poplar under soil water deficits on the Loess Plateau.
AB  - The water consumption characteristics and water use efficiency (WUE) of poplar
      (Populus simonii) were investigated under the condition of three different soil
      water regimes, which were 70%, 55% and 40% of field capacity (FC), respectively.
      The results showed that water potential, water content, photosynthetic rate, WUE
      of leaves, and plant growth rate decreased significantly with reduction in soil
      water content. At the level of adequate and medium soil water content, rapid
      growth and biomass accumulation in poplar occurred during May and June, whereas
      this phenomenon occurred only during May under severe soil drought condition.
      Total water consumption and biomass growth were the greatest under adequate soil
      water condition, decreased under medium soil drought condition, and lowest under
      severe soil drought condition. Total WUE was the highest under medium soil water
      condition and lowest under severe soil condition. Changing patterns of water
      consumption for daily rate, every 10-day rate, and month rate were quite
      different under these three soil water regimes. For all these three treatments,
      the highest monthly water consumption rate occurred during July and June. The
      highest water consumption over a 10-day period was during in the second 10 days
      of July, the first 10 days of July, and the last 10 days of June for these three
      treatments, respectively. The day for the highest water consumption in the medium
      and severe drought treatments occurred 1 or 2 months earlier than the adequate
      soil water treatment. The daily time for the greatest water consumption was
      different throughout the life span of poplar under these soil water levels.
      According to these results, we concluded that poplar did not have the
      characteristics of drought-resistance plants, and we do not recommend that this
      tree species be planted over a wider range of the Loess Plateau in China.

PMID- 16949802
TI  - Contribution of solid-state properties to the aqueous solubility of drugs.
AB  - This study investigates the influence of the solid-state properties melting point
      (T(m)), enthalpy of melting (DeltaH(m)) and entropy of melting (DeltaS(m)) of a
      drug on its intrinsic solubility (S(0)). For this purpose, 26 chemically and
      structurally diverse drugs covering the oral drug space were selected and the
      S(0), T(m), DeltaH(m) and DeltaS(m) were determined experimentally. The influence
      of T(m), DeltaH(m) and DeltaS(m) on S(0) was studied using regression analysis.
      The overall improvement of the predictions were 0.3 log units, however, five
      compounds (astemizole, glyburide, fenbufen, gliclazide and griseofulvin) were
      improved by more than one log unit. T(m) and DeltaH(m) had a larger effect than
      DeltaS(m) on the solubility predictions. The well-known general solubility
      equation (GSE) and the Dannenfelser semi-empirical equation for the calculation
      of DeltaS(m) were evaluated using our data set. While predictions of drug
      solubility obtained using the GSE were acceptable, the use of the experimental
      DeltaS(m) values instead of the constant 56.5 J mol(-1)K(-1) improved the
      accuracy of the prediction. The Dannenfelser equation underestimated the
      DeltaS(m) for most compounds with on average 15 J mol(-1)K(-1). Our results show
      that solid-state properties should be considered for improved performance of
      future models for prediction of drug solubility. In addition our study provides
      accurate experimental data on intrinsic solubility for 26 compounds, supplying a
      useful external data set for validation of drug solubility models.

PMID- 16949803
TI  - Enhanced contractility of small blood vessels in JNK knockout mice.
AB  - The c-Jun N-terminal kinases (JNKs) form a subfamily of the mitogen-activated
      protein kinases (MAPK). These signalling pathways regulate various processes such
      as mitosis, cellular differentiation, stress response or apoptosis in
      multicellular organisms. There is rising evidence about the role of JNKs
      activities in neurodegenerative and metabolic diseases as well as in
      immunological disorders. The physiological functions of JNKs, however, remain to
      be elucidated. Recent data have demonstrated an essential role of JNKs in the
      cardiovascular system and the regulation of carbon hydrate and glucose
      metabolism. Therefore, we have investigated the contractility of blood vessels in
      mice with genetically deleted JNK1, JNK2, JNK3 and JNK2+3 isoforms and their
      respective wildtypes. The contractility of the isolated segments from A. carotis
      communis was measured by small blood vessel wire myograph. Contraction induced by
      80 mM KCl was significantly increased in arteries from JNK2+3 double knockout
      compared to controls and single knockouts. The maximal contraction generated by
      the alpha-agonists phenylephrine or noradrenaline (10 microM) was significantly
      enhanced in JNK2+3 knockout arteries compared with arteries from the remaining
      strains. Inhibition of NOS by Nw-nitro-l-arginine did not change the pattern of
      vasoconstriction, but vasoconstriction by noradrenaline following NOS inhibition
      was significantly enhanced in the arteries from JNK2+3 double knockout mice. In
      conclusion, genetic deletion of JNK2+3 in mice results in altered contractility
      of carotid arteries and this might depend on the function of the smooth muscles
      rather than on the endothelium. These findings have implications for the long
      term treatment with pharmacological JNK inhibitors for neurodegenerative or
      metabolic diseases such as stroke or diabetes.

PMID- 16949804
TI  - Effect of drug type on the degradation rate of PLGA matrices.
AB  - We compare the rate of drug release through the degradation of 50:50 polylactic
      co-glycolic acid polymer pellets, for six different drugs: Thiothixene,
      Haloperidol, Hydrochlorothiozide, Corticosterone, Ibuprofen, and Aspirin. Despite
      using the same polymer matrix and drug loading (20% by weight), we find that the
      rate of polymer degradation and the drug release profile differ significantly
      between the drugs. We conclude that the design of biodegradable polymeric drug
      carriers with high drug loadings must account for the effect of the drug on the
      polymer degradation and drug release rate.

PMID- 16949805
TI  - Further characterization of theobroma oil-beeswax admixtures as lipid matrices
      for improved drug delivery systems.
AB  - There is an increasing interest in lipid based drug delivery systems due to
      factors such as better characterization of lipidic excipients and formulation
      versatility and the choice of different drug delivery systems. It is important to
      know the thermal characteristics, crystal habit, texture, and appearance of a new
      lipid matrix when determining its suitability for use in certain pharmaceutical
      application. It is line with this that this research was embarked upon to
      characterize mixtures of beeswax and theobroma oil with a view to applying their
      admixtures in drug delivery systems such as solid lipid nanoparticles and
      nanostructured lipid carriers. Admixtures of theobroma oil and beeswax were
      prepared to contain 25% w/w, 50% w/w, and 75% w/w of theobroma oil. The
      admixtures were analyzed by differential scanning calorimetry (DSC), small angle
      X-ray diffraction (SAXD), wide angle X-ray diffraction (WAXD), and isothermal
      heat conduction microcalorimetry (IMC). The melting behavior and microstructures
      of the lipid admixtures were monitored by polarized light microscopy (PLM).
      Transmission electron microscopy (TEM) was used to study the internal structures
      of the lipid bases. DSC traces indicated that the higher melting peaks were
      roughly constant for the different admixtures, but lower melting peaks
      significantly increased (p < 0.05). The admixture containing 25% w/w of theobroma
      oil possessed highest crystallinity index of 95.6%. WAXD studies indicated
      different reflections for the different lipid matrices. However, new
      interferences were detected for all the lipid matrix admixtures between 2theta =
      22.0 degrees and 2theta = 25.0 degrees. The lipid matrices containing 50% w/w and
      25% w/w of theobroma oil showed absence of the weak reflection characteristic of
      pure theobroma oil, while there was disappearance of the strong intensity
      reflection of beeswax in all the lipid matrix admixtures at all stages of the
      study. PLM micrographs revealed differences with regard to the thermal and
      optical behaviors depending on the composition of the matrix. The lipid matrix
      consisting of 75% w/w of theobroma oil showed a spherulite texture after 4 weeks
      of isothermal storage. Crystallization exotherms of lipid matrices containing 50%
      w/w and 25% w/w of theobroma oil showed change in modification after 30 min with
      the latter having a greater time-dependent crystallization. Generally, low non
      integral Avrami exponents and growth rate constants were obtained for all the
      lipid matrices, with the admixture containing 25% w/w theobroma oil having the
      lowest Avrami exponent and growth rate constant. Based on the results obtained,
      admixtures containing 50% w/w and 75% w/w of theobroma oil could be applied in
      the formulation of solid lipid nanoparticles and nanostructured lipid carriers as
      these lipid matrices possessed crystal characteristics that favour such drug
      delivery systems.

PMID- 16949806
TI  - The erectile cheek-spine apparatus in the bristlenose catfish Ancistrus
      (Loricariidae, Siluriformes), and its relation to the formation of a secondary
      skull roof.
AB  - In the South American catfish family Loricariidae, the opercle has been decoupled
      from the lower jaw, and has also lost its function in expiration. While many
      loricariid species have a small and slightly mobile opercle with reduced
      opercular musculature, within the hypostomine subfamily a novel opercular
      mechanism has developed that erects a tuft of enlarged odontodes anterior to the
      opercle. This defensive mechanism is examined in Ancistrus cf. triradiatus. The
      opercle has a prominent anterior process and the orientation of the reinforced
      articulation hinge to the hyomandibular bone has shifted. The opercular
      musculature is well developed, with a hypertrophied dilatator operculi that
      extends deep inside the skull roof bones and toward the midline, over the brain,
      but below the superficial skull roof. Hence the frontal, sphenotic, parieto
      supraoccipital and compound pterotic bones consist of a dorsal, superficial part
      and a deeper part separating the brain from the muscle: two functional skull
      roofs are thus formed. The impact on the path of the cranial sensory canals is
      substantial, moving canals away from the skull surface. Hypertrophy of cranial
      muscles is known from many teleosts, but the invasion of such large muscles into
      the skull, which is drastically modified and literally hollowed out, has never
      been described before. These cranial modifications are greater in males than in
      females, related to the territorial behavior of the former, in which the erectile
      spines are usually used.

PMID- 16949807
TI  - Characterization of a newly discovered China variety of Metarhizium anisopliae
      (M. anisopliae var. dcjhyium) for virulence to termites, isoenzyme, and
      phylogenic analysis.
AB  - The efficacy of a new virulent Metarhizium anisopliae variety (M. anisopliae var.
      dcjhyium, DQ288247) obtained from Odontotermes formosanus in China was evaluated
      against the subterranean termite, O. formosanus, in the laboratory. The new
      variety was compared with four other virulent M. anisopliae isolates and was
      found to be highly infectious and virulent against termites. M. anisopliae var.
      dcjhyium could cause approximately 100% mortality of termites 3 days post
      inoculation in the concentration of 3x10(8) conidia/ml. There were also
      differences in relative hyhal growth and isoenzymes. M. anisopliae var. dcjhyium
      showed a different isoenzyme band pattern from the four isolates of M. anisopliae
      (AB027337, AB099510, AB099941 and AF280631). The phylogenetic tree of the 18S
      rDNA sequences revealed the taxonomic and evolutionary position of M. anisopliae
      var. dcjhyium. M. anisopliae var. dcjhyium and four isolates of M. anisopliae
      formed a monophyletic group, supported by a 99% bootstrap value. M. anisopliae
      var. dcjhyium formed a distinct variety, which had a special characterization of
      unique bands of isoenzyme, high virulence and low repellency against termites
      when compared with four other isolates of M. anisopliae.

PMID- 16949808
TI  - Molecular phylogeny supports a Northern Hemisphere origin of Golovinomyces
      (Ascomycota: Erysiphales).
AB  - Golovinomyces is a strictly herb-parasitic genus in the Erysiphaceae. Host
      parasite co-speciation was reported recently between the genus Golovinomyces and
      Asteraceae from molecular phylogenetic analyses. The Asteraceae originated in
      South America and latterly expanded their geographic distribution into the
      Northern Hemisphere. If the co-speciation between Golovinomyces and Asteraceae
      originated in South America, the geographic origin of Golovinomyces could be
      assumed to be South America. To address this question, Golovinomyces species from
      hosts of the tribe Mutisieae, an asteraceous tribe endemic to South America, were
      collected and the ITS and 28S rDNA regions sequenced. Results indicate that
      Oidium mutisiae and Golovinomyces leuceriae isolated from the Mutisieae do not
      belong at the base of the Golovinomyces tree. Instead, they are situated
      separately within two different clades of Golovinomyces isolates from the
      Northern Hemisphere. Therefore, the tribe Mutisieae is not the most early host of
      Golovinomyces. Present results suggest that Golovinomyces originated in the
      Northern Hemisphere, and not in South America. The new species Oidium reginae for
      the previous O. mutisiae on Mutisia decurrens is proposed.

PMID- 16949809
TI  - The history of tuberculosis.
AB  - Tuberculosis has claimed its victims throughout much of known human history. It
      reached epidemic proportions in Europe and North America during the 18th and 19th
      centuries, earning the sobriquet, "Captain Among these Men of Death." Then it
      began to decline. Understanding of the pathogenesis of tuberculosis began with
      the work of Theophile Laennec at the beginning of the 19th century and was
      further advanced by the demonstration of the transmissibility of Mycobacterium
      tuberculosis infection by Jean-Antoine Villemin in 1865 and the identification of
      the tubercle bacillus as the etiologic agent by Robert Koch in 1882. Clemens von
      Pirquet developed the tuberculin skin test in 1907 and 3 years later used it to
      demonstrate latent tuberculous infection in asymptomatic children. In the late
      19th and early 20th centuries sanatoria developed for the treatment of patients
      with tuberculosis. The rest provided there was supplemented with pulmonary
      collapse procedures designed to rest infected parts of lungs and to close
      cavities. Public Health measures to combat the spread of tuberculosis emerged
      following the discovery of its bacterial cause. BCG vaccination was widely
      employed following World War I. The modern era of tuberculosis treatment and
      control was heralded by the discovery of streptomycin in 1944 and isoniazid in
      1952.

PMID- 16949810
TI  - Effect of oxazaborolidines on immobilized fructosyltransferase analyzed by
      surface plasmon resonance.
AB  - Dental diseases are among the most prevalent afflictions of humankind. These
      diseases are associated with the formation of biofilms harboring pathogenic
      bacteria. Fructosyltransferases (FTF) are extra cellular enzymes of several oral
      bacteria. FTF are associated with the formation of extracellular polysaccharide
      matrix (fructans) which play a role in biofilm formation and oral bacteria
      physiology. Oxazaborolidines have been shown to inhibit biofilm formation. The
      purpose of this study was to examine if the anti-biofilm effect is, in part, an
      effect on the immobilized enzymes synthesizing the extra cellular polysaccharide
      participating in biofilm formation. Eight different oxazaborolidines (BNO1-BNO8)
      were synthesized and evaluated for their affect on the synthesis of fructans by
      FTF using the biomolecular interaction analysis (BIAcore) system which involves
      the use of real-time surface plasmon resonance (SPR) technique. The tested
      oxazaborolidines demonstrated a significant and immediate inhibitory effect on
      immobilized FTF activity. This effect was reversible. Our results show that
      oxazaborolidines can act as enzymatic inhibitors of FTF immobilized on the
      surface, also at levels lower than their MIC. Part of the anti-biofilm effect of
      BNOs may be accounted for this enzymatic inhibition.

PMID- 16949811
TI  - At caesarean section under regional anaesthesia, it is essential to test sensory
      block with light touch before allowing surgery to start.

PMID- 16949812
TI  - Women need to be told ALL the risks before regional techniques are performed.

PMID- 16949813
TI  - Recent advances and applications of site-directed spin labeling.
AB  - Site-directed spin labeling has become a popular biophysical tool for the
      characterization of protein structure, dynamics and conformational change. This
      method is well suited and widely used to study small soluble proteins, membrane
      proteins and large protein complexes. Recent advances in site-directed spin
      labeling methodology have occurred in two areas. The first involves an
      understanding of the conformations and local dynamics of the spin-labeled
      sidechain, including the features of proteins that influence electron
      paramagnetic resonance lineshape. The second advance is the application of pulse
      techniques to determine long-range distances and distance distributions in
      proteins. During the past two years, these technical developments have been used
      to address several important problems concerning the molecular function of
      proteins.

PMID- 16949814
TI  - Promising molecular techniques for discriminating among follicular thyroid
      neoplasms.
AB  - To guide the extent of thyroidectomy for indeterminate follicular neoplasm (FN),
      clinicians have long sought ways to differentiate follicular adenoma from
      carcinoma pre- or intraoperatively. Several promising molecular techniques have
      recently appeared including loss of heterozygosity analysis and molecular
      profiling microarray analysis. These new tools may also prove useful in
      determining prognosis, thus and allow a paradigm change in current management of
      the thyroid nodule.

PMID- 16949815
TI  - Agronomic effects of multi-year surface-banding of dairy slurry on grass.
AB  - Sleigh-foot application of slurry manure is the best method for applying slurry
      manure on many forage fields. This study was designed to assess agronomic
      effectiveness of multi-year surface banding of dairy slurry on a sward of tall
      fescue (Festuca arundinacea Schreb.). Our study showed that with this application
      technology, crop recovery of total-N from applied manure in the long-term is only
      about 77% that of mineral fertilizer. Despite relative inefficiency of N uptake
      from manure, yield response to manure equaled that to fertilizer at equivalent
      total-N rates although N-recovery was significantly lower. About 26-32% of
      applied manure-N was stored in soil organic matter and the buildup of soil-N was
      related to application rate of organic N. At moderate applications rates (approx.
      400 kg Nha(-1)a(-1)), soil N accumulated at about 120 kg ha(-1) annually compared
      to 98 kg ha(-1)a(-1) of unaccounted N, much of that probably volatilized and
      denitrified. Alternating between manure and fertilizer improved productivity per
      unit land area without increasing the rate of N non-recovery per unit of feed
      produced.

PMID- 16949816
TI  - An integrated biochemical and physical model for the composting process.
AB  - A dynamic model for the composting process has been developed, which integrates
      several biochemical and physical processes. Different microbial populations
      (mesophilic and thermophilic bacteria, actinomycetes and fungi) have been
      considered, each specialized in certain types of polymeric substrates
      (carbohydrates, proteins, lipids, hemicellulose, cellulose and lignin) and their
      hydrolysis products. Heat and mass transfer between the three phases of the
      system have been taken into account. The gas phase was considered to be composed
      by nitrogen, oxygen, carbon dioxide, ammonia and water vapour. Model computer
      simulations provided results that fitted satisfactory the experimental data. A
      sensitivity analysis was performed to determine the key parameters of the model.
      The partition of both the composting mass and the active biomass into different
      major groups of substrates and specialized microbial populations, as well as the
      factors affecting the gas-liquid equilibrium, were important for an accurate
      description of the composting process.

PMID- 16949817
TI  - Agars of Gelidiella acerosa of west and southeast coasts of India.
AB  - Seventeen agar samples were extracted from Gelidiella acerosa (Forsskal) Feldmann
      and Hamel (Rhodophyta, Gelidiales) specimens collected from nine different sites
      on the Indian coast-five from southeast coast and four from the west coast. The
      agar samples were analysed. The stability characteristics of the gels of selected
      agar samples were studied by rheometry under applied stress conditions, i.e.
      variation of the storage (G') and loss moduli (G'') were studied under varying
      frequency and duration (time) of the stress applied. Yield, apparent and dynamic
      viscosities, gelling and melting temperatures, 3,6-anhydrogalactose (3,6-AG),
      sulphate contents and TGA (Thermogravimetric Analysis) measurements of the
      products were done. It was observed that the best quality agar was produced by G.
      acerosa occurring in the Gulf of Mannar region in the southeast coast. The gel
      strengths and the viscosities of agars extracted from Gelidiella acerosa
      occurring in the Gulf of Mannar ranged from 500 to 700gcm(-2) and 33 to 45cP for
      2001 collections and for 2002 collections the corresponding values were 450 to
      845gcm(-2) and 55 to 67cP respectively. On the other hand, for the agar samples
      extracted from the west coast of India, the gel strength and viscosities values
      ranged from 225 to 400gcm(-2) and from 15 to 30cP, respectively. The agars
      obtained from G. acerosa collected from southeast coast have been found to be
      suitable for bacterial culture and molecular biology. This is the first report of
      superior quality of agar from the Indian agarophytes.

PMID- 16949818
TI  - Potent antagonists of the Kv1.5 potassium channel: synthesis and evaluation of
      analogous N,N-diisopropyl-2-(pyridine-3-yl)acetamides.
AB  - This letter describes the discovery of a novel series of potent Kv1.5 ion channel
      antagonists based on a diisopropyl amide scaffold. Structure-activity
      relationships of functionalized analogs are discussed. Key compound 1-(3
      (diisopropylcarbamoyl)-2-phenyl-3-(pyridin-3-yl)propyl)-3-(2-fluorobenzyl)urea
      (10) exhibits significant atrial-selective effects in an in vivo model.

PMID- 16949819
TI  - Design, total synthesis, and biological evaluation of neodysiherbaine A
      derivative as potential probes.
AB  - To enable studies to elucidate the detailed biological function of dysiherbaine
      and neodysiherbaine A, potent and subunit-selective agonists for ionotropic
      glutamate receptors, the derivative with a hydroxymethyl substituent at the C10
      position has been developed. Preliminary biological evaluation of the analogue
      showed that a C10 hydroxymethyl substituent produced significant alterations in
      binding affinities for the ionotropic glutamate receptor subtypes.

PMID- 16949820
TI  - A novel 99mTc-labeled testosterone derivative as a potential agent for targeting
      androgen receptors.
AB  - With an insight that ligands possessing a N2S2 tetradentate array of donor atoms
      serve as ideal bifunctional chelating agents (BFCA) in the radiolabeling of
      target-specific agents, 5-hydroxy-3,7-diazanonan-1,9-dithiol (DAHPES) with a
      derivatizable substituent in the form of a hydroxyl group in the backbone was
      synthesized. The preparation of a steroid conjugate via coupling of this BFCA
      with testosterone-3-(O-carboxymethyl) oxime and the subsequent radiolabeling of
      the conjugate under optimized conditions with 99mTc, the ideal diagnostic
      radionuclide in nuclear medicine procedures, are reported. The immunoreactivity
      of the radiolabeled conjugate was demonstrated in a study using anti-testosterone
      antibodies, wherein the radiolabeled conjugate exhibited significant binding with
      antiserum to testosterone. Cell-uptake studies in DU145 prostate carcinoma cell
      line bearing androgen receptors (ARs) and comparison with AR non-bearing breast
      carcinoma cell line revealed the specific binding of the steroidal moiety with
      the testosterone receptor.

PMID- 16949821
TI  - The bantam microRNA is a target of the hippo tumor-suppressor pathway.
AB  - BACKGROUND: The Hippo tumor-suppressor pathway has emerged as a key signaling
      pathway that controls tissue size in Drosophila. Hippo signaling restricts tissue
      size by promoting apoptosis and cell-cycle arrest, and animals carrying clones of
      cells mutant for hippo develop severely overgrown adult structures. The Hippo
      pathway is thought to exert its effects by modulating gene expression through the
      phosphorylation of the transcriptional coactivator Yorkie. However, how Yorkie
      regulates growth, and thus the identities of downstream target genes that mediate
      the effects of Hippo signaling, are largely unknown. RESULTS: Here, we report
      that the bantam microRNA is a downstream target of the Hippo signaling pathway.
      In common with Hippo signaling, the bantam microRNA controls tissue size by
      regulating cell proliferation and apoptosis. We found that hippo mutant cells had
      elevated levels of bantam activity and that bantam was required for Yorkie-driven
      overgrowth. Additionally, overexpression of bantam was sufficient to rescue
      growth defects of yorkie mutant cells and to suppress the cell death induced by
      Hippo hyperactivation. Hippo regulates bantam independently of cyclin E and
      diap1, two other Hippo targets, and overexpression of bantam mimics overgrowth
      phenotypes of hippo mutant cells. CONCLUSIONS: Our data indicate that bantam is
      an essential target of the Hippo signaling pathway to regulate cell
      proliferation, cell death, and thus tissue size.

PMID- 16949822
TI  - The role of PIWI and the miRNA machinery in Drosophila germline determination.
AB  - BACKGROUND: The germ plasm has long been demonstrated to be necessary and
      sufficient for germline determination, with translational regulation playing a
      key role in the process. Beyond this, little is known about molecular activities
      underlying germline determination. RESULTS: We report the function of Drosophila
      PIWI, DICER-1, and dFMRP (Fragile X Mental Retardation Protein) in germline
      determination. PIWI is a maternal component of the polar granule, a germ-plasm
      specific organelle essential for germline specification. Depleting maternal PIWI
      does not affect OSK or VASA expression or abdominal patterning but leads to
      failure in pole-plasm maintenance and primordial-germ-cell (PGC) formation,
      whereas doubling and tripling the maternal piwi dose increases OSK and VASA
      levels correspondingly and doubles and triples the number of PGCs, respectively.
      Moreover, PIWI forms a complex with dFMRP and DICER-1, but not with DICER-2, in
      polar-granule-enriched fractions. Depleting DICER-1, but not DICER-2, also leads
      to a severe pole-plasm defect and a reduced PGC number. These effects are also
      seen, albeit to a lesser extent, for dFMRP, another component of the miRISC
      complex. CONCLUSIONS: Because DICER-1 is required for the miRNA pathway and DICER
      2 is required for the siRNA pathway yet neither is required for the rasiRNA
      pathway, our data implicate a crucial role of the PIWI-mediated miRNA pathway in
      regulating the levels of OSK, VASA, and possibly other genes involved in germline
      determination in Drosophila.

PMID- 16949823
TI  - Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking.
AB  - Rho GTPases are well known to regulate actin dynamics. They activate two types of
      actin nucleators, WASP/WAVE proteins and Diaphanous-related formins (DRFs), which
      induce different types of actin organization. Their ability to interact with
      membranes allows them to target actin polymerization to discrete sites on the
      plasma membrane and to intracellular membrane compartments and thereby induce
      membrane protrusions or regulate vesicle movement. Most studies have concentrated
      on just three of the 22 mammalian Rho proteins, RhoA, Rac1 and Cdc42. However,
      recent research indicates that several other members of the Rho family, including
      Rif, RhoD, TC10 and Wrch1, and also related Rho-of-plants proteins (ROPs) in
      plants, stimulate actin polymerization and affect plasma membrane protrusion
      and/or vesicular traffic.

PMID- 16949824
TI  - Bar domain proteins: a role in tubulation, scission and actin assembly in
      clathrin-mediated endocytosis.
AB  - Endocytosis is an important way for cells to take up liquids and particles from
      their environment. It requires membrane bending to be coupled with membrane
      fission, and the actin cytoskeleton has an active role in membrane remodelling.
      Here, we review recent research into the function of Bin-Amphiphysin-Rvs (BAR)
      domain proteins, which can sense membrane curvature and recruit actin to
      membranes. BAR proteins interact with the endocytic and cytoskeletal machinery,
      including the GTPase dynamin (which mediates vesicle fission), N-WASP (an Arp2/3
      complex regulator) and synaptojanin (a phosphoinositide phosphatase). We describe
      three classes of BAR domains, BAR, N-BAR and F-BAR, providing examples of each
      discussing and how they function in linking membranes to the actin cytoskeleton
      in endocytosis.

PMID- 16949825
TI  - Experiences of adding nurses to increase medical competence at an emergency
      medical dispatch centre.
AB  - INTRODUCTION: Prehospital care begins when the call is placed to the emergency
      medical dispatch (EMD) centre and ends when the patient is cared for at the
      emergency department. The highly technical and specialized character demands
      advanced medical competence. Communication problems, serious and unpredictable
      situations can often occur during the emergency calls. A two-year intervention
      study involved the addition of registered nurses to an EMD-centre team to
      increase medical competence. AIM: To describe registered nurses' and emergency
      operators' experiences of working together at an EMD-centre after adding
      registered nurses to increase medical competence. METHODS: Qualitative content
      analysis was used to analyse the text from interviews with four registered nurses
      and 15 emergency-operators involved in the intervention. RESULTS: Initial
      frustration and scepticism changed to more positive experiences that resulted in
      improved cooperation and service. The registered nurses had difficulties dealing
      with the more urgently acute calls, while the emergency-operators had
      difficulties with the more complicated, somewhat diffuse cases. The two
      professions complemented each other. CONCLUSION: Combining the registered nurses'
      and emergency-operators' knowledge and experience at an EMD-centre can perhaps
      improve the prehospital care for those requiring emergency medical care.

PMID- 16949826
TI  - The effect of simulated hamstring shortening on gait in normal subjects.
AB  - The purpose of this study was to determine the effect of simulated hamstring
      shortening on gait in normal subjects. Six normal subjects wore an adjustable
      brace to simulate three different hamstring lengths. Evaluation of the
      physiological cost index (PCI) and gait analysis revealed that simulated
      hamstring shortening produced adverse affects in the gait of normal subjects.
      Significant effects were only observed when the popliteal angle exceeded 85
      degrees (p<0.001) and included increased effort of walking (PCI), decreased
      speed, stride and step length; decreased hip flexion and increased knee flexion
      in stance, increased posterior pelvic tilt, decreased pelvic obliquity and
      rotation and premature ankle dorsi- and plantar-flexion in stance. These results
      emphasise the need to consider the effects of changing the length of the
      hamstrings on joints other than the hip and knee when assessing patients for
      hamstring lengthening.

PMID- 16949827
TI  - Stepping responses made by elderly and young female adults to approach and
      accommodate known surface height changes.
AB  - Falls on stairs, kerbs and footpaths are a major cause of morbidity in older
      female adults. This investigation examined the stepping responses made by 48
      elderly (mean age 67 years, S.D. 5.4 years) and 48 young (mean age 20 years, S.D.
      2.4 years) healthy, community-dwelling adult females to approach and accommodate
      known surface height changes. The surface was designed to simulate an object like
      a kerb or step in the walking path. For ascent, the surface was 9 m long (height,
      15 cm) with a 13 m ground-level approach. For descent, it was 15m long (height,
      15 cm) with a 7 m ground-level departure. These tasks (particularly descent)
      perturbed the gait of the elderly more than the young. The elderly exerted more
      control or were more cautious. They made earlier and larger step adjustments
      (p<.05), primarily employed a short step crossing strategy (elderly, 60%; young,
      19%), exhibited less footfall variability (p<.05), moved slower across the step
      (p<.001) and spent more time in double foot support while crossing the step. In
      descent, the elderly preferred to land on the forefoot (p<.001). In both
      conditions, the elderly placed the feet closer to the step and cleared it by a
      lesser margin. Step descent appears to be particularly hazardous for older
      females since foot clearances were small and foot placement was closer to the
      step.

PMID- 16949829
TI  - Mitral valve motion assessed by high-speed video camera in isolated swine heart.
AB  - OBJECTIVE: We have recently reported our isolated and working swine heart model
      that examines the valve motion precisely by a high-speed digital video camera
      system. Using this modality, the present study aimed (1) to delineate the motion
      of the mitral leaflets, chords and annulus throughout the cardiac cycle, and (2)
      to elucidate the influence of alterations in loading conditions on leaflet
      excursion. METHODS: The valve motion of five isolated and working swine hearts
      was observed by an endoscope recording the images at 250 frames per second.
      Modified Krebs-Ringer solution was used as the sole perfusate. The images were
      obtained in hearts 30 min after reperfusion, changing the left atrial pressure as
      4, 8, and 12 mmHg. RESULTS: The motion of the mitral valve in the vicinity of
      diastole was considered to be well understood by dividing the entire sequence
      into five stages: 'decoaptation,' 'E excursion,' 'diastasis,' 'A excursion,' and
      'coaptation.' Initial separation occurred at both sides of the central tips of
      the leaflets. The leading edges always followed the mid-portion of the rough zone
      during opening and closing. The 'strut' second-order chords retained their
      tension throughout the cardiac cycle and played the role as rotary shafts of the
      other branching chords. The first-order chords lost their tension during opening,
      suggesting they mainly are involved in valve competence. Annular constriction
      occurred coincident with atrial contraction. An increase in preload made the
      isovolumic relaxation and contraction times shorter. The leaflets opened faster
      in the rapid-filling phase, whereas they required more time for opening and
      closing in the atrial-filling phase. CONCLUSIONS: The present study revealed the
      integrated movement of the mitral leaflets, chords and annulus, as well as the
      impact of altered preload.

PMID- 16949828
TI  - Identification of 2-hydroxymethyl-4-[5-(4-methoxyphenyl)-3-trifluoromethyl
      pyrazol-1-yl]-N-propionylbenzenesulfonamide sodium as a potential COX-2 inhibitor
      for oral and parenteral administration.
AB  - Synthesis of prodrugs of orally active COX-2 inhibitor 3 involving sulfamoyl
      (SO(2)NH(2)) and hydroxymethyl (CH(2)OH) groups, and their biological evaluation
      are described. Of these prodrugs, the N-propionyl sulfonamide sodium 3k was found
      to be much superior to the parent compound 3 and other marketed COX-2 inhibitors
      in carrageenan induced rat paw edema model of inflammation due to highly elevated
      drug levels in systemic circulation. This prodrug has a potential both for oral
      as well as parenteral administration due to impressive analgesic activity,
      antipyretic potency, and extraordinary water solubility.

PMID- 16949830
TI  - The role of leukocyte depleting filters in heart transplantation: early outcomes
      in prospective, randomized clinical trial.
AB  - OBJECTIVE: Leukocyte-mediated reperfusion injury to cardiac allograft in the
      perioperative period is most likely associated with the early and late mortality
      after heart transplantation (Htx). Our aim is to determine the efficacy and
      safety of using leukocyte-depleting filters in a cardiopulmonary bypass (CPB) and
      secondary blood cardioplegia (SBC) circuit in Htx. METHODS: A prospective,
      randomized trial was performed in 40 patients undergoing orthotopic Htx. These
      patients were divided into two groups, to be treated with either leukocyte
      depleted (LD) reperfusion (n=20) in the LD group, or whole blood reperfusion
      (n=20) in the Control group. The SBC was used in both groups. RESULTS:
      Intraoperatively, the LD group presented the reduced markers of reperfusion
      injury. The course of the creatine kinase MB (CK-MB) releases was significantly
      lower in the LD group (p<0.05). The LD hearts showed better spontaneous rhythm
      resumption (60% vs 10%; p<0.001), and lower need for isoprenaline (0.02+/-0.01
      microg/(kg min) vs 0.03+/-0.02 microg/(kg min); p<0.05) and epicardial pacing
      (25% vs 60%; p<0.05) for weaning off CPB. Postoperatively, lower and shorter need
      for inotropic support (48+/-46, median=35 h vs 131+/-68, median=109 h; p<0.001),
      shorter temporary epicardial pacing (6+/-14, median=0 h vs 25+/-52, median=1 h;
      p<0.01), and lower 24-h chest drainage (551+/-274, median=500 ml vs 973+/-836,
      median=665 ml; p<0.05) in the LD group contributed to the shorter mechanical
      ventilation time (8+/-3, median=7.5 h vs 14+/-12, median=8.5 h; p<0.05) and the
      shorter stay at an intensive care unit (ICU) (70+/-24 h vs 116+/-73 h; p<0.05).
      The 30-day mortality was zero in both groups. CONCLUSIONS: The use of leukocyte
      depleting filters in heart transplantation is an effective, easy and safe method
      of myocardial protection, reducing significant myocardial reperfusion injury and
      improving posttransplant graft functional recovery.

PMID- 16949831
TI  - Right upper lobe 'window' in right main bronchus stenting.
AB  - Stent insertion for bronchial stenosis has become common practice in lung
      transplantation and advanced lung malignancy, and for external compression of the
      airways for other reasons. Right main bronchus stenting may require blocking the
      right upper lobe by the stent, placing the patient at risk of recurrent pneumonia
      and atelectasis. In this study, three patients after insertion of a metal stent
      to the right main bronchus are described. In all cases, the right upper lobe was
      covered by the stent, and a laser (Nd:YAG) procedure was used to open a 'window'
      in the stent toward the right upper lobe with a follow-up of 1 year. We conclude
      that stent insertion to the right main bronchus may be followed by a laser
      therapy to open a 'window' toward the right upper lobe.

PMID- 16949832
TI  - Locally advanced and metastatic sarcoma (adult type) including gastrointestinal
      stromal tumors.
AB  - STS belong to the most challenging diseases in oncology that demand all resources
      of modern clinical oncology. With the improvement of surgical techniques and
      radiation therapy the majority of patients with localized disease can be cured.
      However, for patients with locally advanced or metastatic disease
      chemotherapeutic treatments have not greatly changed the poor outcome of the
      disease. The introduction of combined chemoradiotherapy as well as isolated limb
      perfusion has improved the limb-salvage rate in locally advanced disease but the
      impact of systemic chemotherapy on overall survival remains a subject of dispute.
      For patients with metastatic sarcoma long-term survival can only be achieved in a
      small number of patients with mostly resectable disease. The list of effective
      drugs for palliative treatment in general still remains short and the duration of
      remissions usually does not exceed several months. The lack of alternative
      chemotherapeutic drugs imposes a considerable challenge in daily clinical
      practice with many young patients exhibiting a good performance status but
      progressive disease after standard treatment. A variety of new drugs or drug
      combinations seem to exhibit considerable activity in certain histological
      sarcoma subtypes, which may soon broaden the armamentarium of drugs for a subset
      of patients. However, with the vastly improved understanding of the biology and
      pathology of soft tissue sarcoma an era of opportunities seems to have begun and
      the recent success in the treatment of gastrointestinal stromal tumors
      impressively shows how fast a gain in the understanding of oncogenic mechanisms
      may translate into a highly efficient, clinically useful treatment.

PMID- 16949833
TI  - Protein tyrosine phosphatase 1B regulates TGF beta 1-induced Smad2 activation
      through PI3 kinase-dependent pathway.
AB  - Insulin is known to modulate transforming growth factor-beta (TGFbeta) signaling.
      In this report, by using the IN Cell Analyzer 1000, the fluorescence cell imaging
      instrument, we demonstrated that protein tyrosine phosphatase 1B (PTP1B) could
      regulate TGFbeta1-induced Smad2 activation in a PI3 kinase-dependent manner. By
      using the CHO cells stably expressing EGFP-Smad2, we showed that TGFbeta1
      effectively stimulated Smad2 nuclear translocation in CHO cells. When pretreated
      with insulin, TGFbeta1-induced Smad2 nuclear entry was dramatically decreased.
      Furthermore, both the PI3K inhibitor LY294002 and the dominant negative AKT (DN
      AKT) abolished the inhibitory effects of insulin, demonstrating that the
      inhibition of Smad2 activation by insulin was PI3K/AKT dependent. Since PTP1B
      negatively modulates insulin signaling, we further addressed the effects of PTP1B
      on insulin-mediated inhibition of Smad2 activation. Our data showed that
      overexpression of PTP1B effectively attenuated insulin-induced inhibition of
      Smad2 stimulation. Moreover, the PTP1B inhibitor, 3-(3,5-dibromo-4-hydroxy
      benzoyl)-2-ethyl-benzofuran-6-sulfonicacid-(4-(thiazol-2-ylsulfamyl)-phenyl)
      amide (Compound-2), recovered insulin inhibition of Smad2 activation. In
      conclusion, our data revealed the insulin inhibitory effects on TGFbeta1-induced
      Smad2 activation and the regulation role of PTP1B in the inhibition events.

PMID- 16949834
TI  - Thyroxine replacement dose in patients with Hashimoto disease: a potential role
      for interleukin-6.
AB  - OBJECTIVE: To investigate the potential association between serum inflammatory
      cytokine levels and thyroxine replacement dose in patients with Hashimoto
      disease. PATIENTS AND METHODS: The study included 40 patients (12 men) with a
      mean age of 56.52+/-6.12 years who had hypothyroidism due to Hashimoto disease.
      Serum interleukin-1b (IL-1b), tumour necrosis factor alpha (TNF-alpha) and
      interleukin-6 (IL-6) levels, as well as TSH, T(3) and T(4) were measured (ELISA).
      RESULTS: Serum IL-6 showed a significant positive correlation both with total
      thyroxine replacement dose (r=0.551, p=0.001) and with dose per kilogram of body
      weight (r=0.482, p=0.002). There was also a significant negative linear
      correlation between serum IL6 and T(3) (r=-0.322, p=0.043), as well as between
      serum IL6 and T(3)/T(4) ratio (r=-0.332, p=0.036). A further significant
      (r=0.419, p=0.007) positive association was demonstrated between IL6 and TNF
      alpha. However, no association was found between T(3) or T(3)/T(4) ratio and TNF
      alpha or IL1b. CONCLUSIONS: In patients with Hashimoto disease serum IL-6 levels
      are positively associated with thyroxine replacement dose and negatively
      associated with T(3) and T(3)/T(4) ratio. These results are possibly attributable
      to the inhibitory effect of IL6 on deiodination of T(3) and imply a role for IL6
      in determining thyroxine replacement dose among these patients.

PMID- 16949835
TI  - Roles of p38 and ERK MAP kinases in IL-8 expression in TNF-alpha- and
      dexamethasone-stimulated human periodontal ligament cells.
AB  - Orthodontic tooth movement is recognized as a pro-inflammatory stressor of human
      periodontal ligament (hPDL) cells. However, the cell-signaling pathways linking
      interleukin-8 (IL-8), intercellular adhesion molecule-1 (ICAM-1), pro
      inflammatory cytokines, and dexamethasone in hPDL cells have not been well
      elucidated. In this study, we investigated the role of mitogen-activated protein
      (MAP) kinases in dexamethasone- and TNF-alpha-induced IL-8 and ICAM-1 expression
      in hPDL cells. IL-8 production was measured by enzyme-linked immunosorbent assay
      (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis.
      MAP kinase activation and IkappaB degradation were determined by Western blot
      analysis, and ICAM-1 expression was determined by RT-PCR and FACS analysis. TNF
      alpha increased IL-8 mRNA expression and protein secretion in a dose- and time
      dependent manner. Dexamethasone suppressed TNF-alpha-induced IL-8 production in a
      dose-dependent manner. In addition, dexamethasone inhibited TNF-alpha-induced
      phosphorylation of p38 MAP kinase and extracellular-regulated kinases (ERKs),
      IkappaB degradation, and NF-kappaB activation. Selective inhibitors for ERKs and
      p38 attenuated TNF-alpha-induced IL-8 and ICAM-1 expression in the presence and
      absence of dexamethasone, indicating that MAP kinases play a role in the response
      of hDPL cells to TNF-alpha. Furthermore, these results suggest that inflammatory
      cytokine- and dexamethasone-induced IL-8 and ICAM-1, produced via a MAP kinase
      pathway, may serve as an important mediator of PDL immunoregulation involved in
      bone remodeling during orthodontic tooth movement.

PMID- 16949836
TI  - The Drosophila microtubule associated protein Futsch is phosphorylated by
      Shaggy/Zeste-white 3 at an homologous GSK3beta phosphorylation site in MAP1B.
AB  - The Drosophila homologue of the microtubule associated protein MAP1B is encoded
      by the futsch locus. The deduced protein Futsch is about twice the size of MAP1B
      and shows high homology in the N- and C-terminal domains. The central part of
      Futsch is characterized by a highly repetitive structure based on a 37 amino acid
      motif. Futsch, like MAP1B, colocalizes with microtubules and is necessary for the
      organization of the microtubule cytoskeleton during axonal growth and
      synaptogenesis. To further analyze the functional relevance of Futsch as a MAP1B
      like protein, we performed a molecular analysis of the conserved protein domains.
      Using a number of antisera, we show that, unlike the MAP1B polyprotein, which is
      cleaved to generate a heavy and light chain, Futsch is expressed as a single
      protein. The function of MAP1B is in part regulated by phosphorylation mediated
      by kinases that include casein kinase 2 and glycogen synthase kinase 3beta
      (GSK3beta). We show here that at least one GSK3beta phosphorylation site of MAP1B
      is conserved in Futsch and that this site can be phosphorylated by GSK3beta and
      its Drosophila homologue, Shaggy/Zeste-white 3. To test the functional relevance
      of these findings we generated a number of minigenes and assayed their ability to
      rescue the phenotype of futsch mutants. Our data highlight some differences
      between MAP1B and Futsch but demonstrate that important structural and functional
      aspects are conserved between fly and vertebrate members of this protein family.

PMID- 16949837
TI  - Properties and expression of Kv3 channels in cerebellar Purkinje cells.
AB  - In cerebellar Purkinje cells, Kv3 potassium channels are indispensable for firing
      at high frequencies. In Purkinje cells from young mice (P4-P7), Kv3 currents,
      recorded in whole-cell in slices, activated at -30 mV, with rapid activation and
      deactivation kinetics, and they were partially blocked by blood depressing
      substance-I (BDS-I, 1 microM). At positive potentials, Kv3 currents were slowly
      but completely inactivating, while the recovery from inactivation was about
      eightfold slower, suggesting that a previous firing activity or a small change of
      the resting potential could in principle accumulate inactivated Kv3 channels,
      thereby finely tuning Kv3 current availability for subsequent action potentials.
      Single-cell RT-PCR analysis showed the expression by all Purkinje cells (n=10 for
      each subunit) of Kv3.1, Kv3.3 and Kv3.4 mRNA, while Kv3.2 was not expressed.
      These results add to the framework for interpreting the physiological function
      and the molecular determinants of Kv3 currents in cerebellar Purkinje cells.

PMID- 16949838
TI  - Mechano-sensory organ regeneration in adults: the zebrafish lateral line as a
      model.
AB  - In this report, we present a study of regeneration of the lateral line, a
      collection of mechano-sensory organ, in the adult zebrafish caudal fin. As all
      neuromasts are innervated by axon fibers, neuronal regeneration is a key issue in
      the regenerating process. We first show that support cells from the last
      neuromast adjacent to the amputation plane divide and migrate to colonize the
      blastema in order to reform the missing part of the lateral line. We then show
      that nerve re-growth takes place later than neuromast progenitor cell migration.
      We also provide evidence that new growth cones form at the amputation plane and
      subsequently follow the migrating placode-like structure to re-innervate
      regenerated neuromasts as they differentiate. Altogether, our observations
      indicate that caudal lateral line regeneration is not a mere recapitulation of
      the ontogenic process.

PMID- 16949839
TI  - Perirhinal cortex activity during visual object discrimination: an event-related
      fMRI study.
AB  - Previous fMRI studies have demonstrated preferential involvement of the
      perirhinal cortex and hippocampus in tasks of object and spatial memory,
      respectively. Here we investigated whether similar activity would also be present
      when object and spatial discrimination was assessed in the absence of explicit
      declarative memory demands. On each trial in the scanner, participants were
      presented simultaneously with two arrays of objects and were asked to indicate
      whether both arrays were identical, differed with respect to the identity of one
      object or differed with respect to the spatial arrangement of the objects. It was
      found that the detection of an object identity change was associated with
      significant right perirhinal cortex activity. We suggest that this perirhinal
      activity indicates a role of this structure in processes beyond declarative
      memory, for example, short-term visual working memory or higher order perception.
      Significantly greater hippocampal activity was not, however, observed during the
      spatial arrangement condition, perhaps due to the relatively low spatial
      processing demands of this task.

PMID- 16949840
TI  - Interscalene block anesthesia at an ambulatory surgery center performing
      predominantly regional anesthesia: a prospective study of one hundred thirty
      three patients undergoing shoulder surgery.
AB  - Interscalene block (ISB) of the brachial plexus is frequently used for patients
      undergoing ambulatory shoulder surgery. We previously reported that the incidence
      of postoperative complaints (neurapraxia) after an ISB was low (3% at 2 weeks),
      but objective neurologic assessment was not included in the study. The present
      study combines subjective findings with both preoperative and postoperative
      objective sensory and motor assessments after an ISB. We prospectively evaluated
      133 patients undergoing elective ambulatory shoulder surgery. ISB anesthesia was
      accomplished by use of 1.5% mepivacaine alone or in combination with bupivacaine
      (0.5%-0.75%) via a paresthesia technique and a 23-gauge needle. All of the blocks
      were performed by experienced anesthesiologists. The number of passes with the
      needle, site of paresthesia, ease of performing the block, and success of the ISB
      were recorded for each patient. Neurologic assessment was performed
      preoperatively and up to 2 weeks postoperatively by 1 of 4 health care
      professionals but not by the anesthesiologists who performed the ISB and included
      diminished sensation, localized nerve pain, Semmes-Weinstein monofilament
      pressure threshold sensibility, Weber static 2-point discrimination, and grip
      strength changes. Patients with postoperative changes were followed up until
      resolution of symptoms occurred. Successful surgical anesthesia was achieved in
      98% of the patients. There was 1 major perioperative complication (0.7%), a
      seizure that occurred within 5 minutes of the ISB. Two (1.4%) complained of
      transient postoperative neurapraxias. Neither patient had any changes in
      objective sensory and motor measurements. Hence, there was no correlation between
      subjective complaints and objective findings in this study. This study
      demonstrates that, in the hands of anesthesiologists doing predominantly regional
      anesthesia, there is a 1.4% incidence of neurologic complications after an ISB.
      ISB is a safe and effective technique for patients undergoing ambulatory shoulder
      surgery when an anesthesiologist experienced with regional anesthesia is
      involved.

PMID- 16949841
TI  - Quantification of ankle articular cartilage topography and thickness using a high
      resolution stereophotography system.
AB  - OBJECTIVE: To describe the topography and to measure thicknesses, surface areas
      and volumes in the cartilage layers of the ankle. METHODS: Twelve cadaveric ankle
      joints were disarticulated and the cartilage surfaces of each bone were imaged
      with a highly accurate (+/-2 microm) stereophotography system (ATOS). The
      cartilage was then dissolved and the subchondral bone imaged. The geometric data
      were then used to measure the quantitative parameters in each cartilage layer.
      RESULTS: The mean cartilage volume across the 12 specimens ranged from 0.32+/
      0.08 ml for the fibula to 2.44+/-0.48 ml for the talus. The mean thickness of
      both the talar (1.1+/-0.18 mm) and tibial (1.16+/-0.14 mm) cartilage was
      significantly thicker than the fibula (0.85+/-0.13 mm). The talus had the
      greatest mean maximum cartilage thickness (2.38+/-0.4 mm). CONCLUSIONS: The
      reported stereophotographic technique may be used as an independent gold standard
      for validation of the accuracy of quantitative cartilage measurements made using
      magnetic resonance imaging. The thickness distribution maps show that the
      thickest articular cartilage occurs over the talar shoulders where osteochondral
      lesions commonly occur and not in the centre of the talar dome as commonly
      believed.

PMID- 16949842
TI  - Different transformation pathways of murine fibroblast NIH 3T3 cells by hepatitis
      C virus core and NS3 proteins.
AB  - The oncogenic potential of both Hepatitis C virus (HCV) core and HCV NS3 proteins
      has been demonstrated, but these proteins induce transformation of immortal
      murine fibroblasts NIH 3T3 via different pathways. As long-term expression (50
      100 passages) of HCV core triggers neoplastic transformation of NIH 3T3 through
      crisis of growth, HCV NS3 induces transformation shortly after transfection. We
      explain this distinction by different effects of core and NS3 on p53-mediated
      transactivation: inhibition by NS3 and activation by core protein.

PMID- 16949843
TI  - Subdural hematoma in a teenager related to roller-coaster ride.
AB  - Reports about neurological injury related to roller-coaster rides mostly involve
      adults; we present a case of subdural hematoma in a pediatric patient presented
      14 days after a roller-coaster ride. These rides show extreme up-and-down, to-and
      fro, and rotatory acceleration/deceleration forces that could produce tensile and
      shearing stresses with tearing of bridging cerebral veins resulting in subdural
      hemorrhage. Pediatricians should consider roller-coaster riding a modern cause of
      subdural hematoma, as well as a possible cause of unexplained neurologic events
      in otherwise healthy adolescents.

PMID- 16949844
TI  - Benefit of glucocorticosteroid in the routine therapy of bacterial meningitis in
      children.
AB  - Based on the most recent randomised-controlled studies, meta-analysis, and
      observational studies, the use of corticosteroids is recommended in most cases of
      acquired community purulent meningitis in children from industrialised countries,
      in order to reduce the incidence of severe deafness and likely of other
      neurological morbidities.

PMID- 16949845
TI  - On the accurate measurement of amide one-bond 15N-1H couplings in proteins:
      effects of cross-correlated relaxation, selective pulses and dynamic frequency
      shifts.
AB  - Amide one-bond 15N-1H scalar couplings of 15N- and [15N,2H]-isotopically enriched
      ubiquitin have been measured with the Quantitative J approach by monitoring NMR
      signal intensity modulation. Scalar couplings of the non-deuterated protein are
      in average approximately 0.6 Hz larger than values of deuterated ubiquitin. This
      deviation is 30 times the error derived from experiment reproducibility.
      Refocusing dipole/dipole cross-correlated relaxation decreases the discrepancy to
      approximately 0.1 Hz, suggesting that it likely originates from relaxation
      interference. Alternatively, the subtraction of J values obtained at different
      magnetic fields largely reduces the relaxation effects. In contrast, the dynamic
      frequency shift whose main contribution to 1J(15N-1H) arises from 15N chemical
      shielding anisotropy/NH dipole cross-correlation, is not eliminated by refocusing
      spin evolution under this interaction. Furthermore, the average difference of
      1J(15N-1H) values at two magnetic fields closely agrees with the theoretical
      expected difference in the dynamic frequency shift.

PMID- 16949847
TI  - Control of breathing in anuran amphibians.
AB  - The primary role of the respiratory system is to ensure adequate tissue
      oxygenation, eliminate carbon dioxide and help to regulate acid-base status. To
      maintain this homeostasis, amphibians possess an array of receptors located at
      peripheral and central chemoreceptive sites that sense respiration-related
      variables in both internal and external environments. As in mammals, input from
      these receptors is integrated at central rhythmogenic and pattern-forming
      elements in the medulla in a manner that meets the demands determined by the
      environment within the constraints of the behavior and breathing pattern of the
      animal. Also as in mammals, while outputs from areas in the midbrain may modulate
      respiration directly, they do not play a significant role in the production of
      the normal respiratory rhythm. However, despite these similarities, the breathing
      patterns of the two classes are different: mammals maintain homeostasis of
      arterial blood gases through rhythmic and continuous breathing, whereas
      amphibians display an intermittent pattern of aerial respiration. While the
      latter is also often rhythmic, it allows a degree of fluctuation in key
      respiratory variables that has led some to suggest that control is not as tight
      in these animals. In this review we will focus specifically on recent advances in
      studies of the control of ventilation in anuran amphibians. This is the group of
      amphibians that has attracted the most recent attention from respiratory
      physiologists.

PMID- 16949846
TI  - Arginine vasotocin, isotocin and melatonin responses following acclimation of
      gilthead sea bream (Sparus aurata) to different environmental salinities.
AB  - Gilthead sea bream (Sparus aurata) is a euryhaline species with a capacity to
      cope with demands in a wide range of salinities and thus is a perfect model-fish
      to study osmoregulatory responses to salinity-adaptive processes and their
      hormonal control. Immature sea bream acclimated to different salinities, i.e. SW
      (38 per thousand), LSW (5 per thousand) and HSW (55 per thousand), were kept at
      18 degrees C under natural photoperiod. Arginine vasotocin (AVT) and isotocin
      (IT) in plasma and pituitary were determined by HPLC. Plasma melatonin (Mel) was
      assayed by RIA. Plasma osmolality, ion concentrations (Na(+), K(+), Ca(2+), Cl(
      )) and Na(+),K(+)-ATPase activity in gill were measured. A steady increase in
      plasma AVT, along with increasing water salinity was observed. Pituitary IT
      concentration in HSW-acclimated fish was significantly higher than that in LSW
      group. AVT/IT secretory system of sea bream does appear to be involved in the
      mechanism of long-term acclimation to different salinities. The distinct roles
      and control mechanisms of both nonapeptides are suggested. Plasma Mel was
      significantly higher in LSW compared with both HSW and SW groups. Data indicate
      that the changes in Mel level are linked to osmoregulation. Further studies are
      required to elucidate a complex role of AVT, IT and Mel in sea bream
      osmoregulation.

PMID- 16949848
TI  - Prevalence of Bartonella henselae antibodies in serum of cats with and without
      clinical signs of central nervous system disease.
AB  - Bartonella henselae is occasionally associated with neurological dysfunction in
      people and some experimentally infected cats. The purpose of this study was to
      determine whether B henselae seroprevalence or titer magnitude varies among cats
      with neurological disease, cats with non-neurological diseases, and healthy cats
      while controlling for age and flea exposure. There was no difference in B
      henselae seroprevalence rates between cats with seizures and cats with other
      neurological diseases. Cats with non-neurological disease and healthy cats were
      more likely than cats with neurological disease to be seropositive. While the
      median B henselae antibody titer was greater in cats with seizures than in cats
      with other neurological disease, the median B henselae antibody titer was also
      greater in healthy cats than cats with seizures. The results suggest that titer
      magnitude cannot be used alone to document clinical disease associated with B
      henselae infection and that presence of B henselae antibodies in serum of cats
      with neurological disease does not prove the clinical signs are related to B
      henselae.

PMID- 16949849
TI  - [Radical surgery for mesothelioma].
AB  - Good results obtained by the team from Boston increased the interest in
      pleuropneumonectomy for mesothelioma. Adjuvant high-dose hemithoracic radiation
      after surgical resection decreased the local recurrence rate from 35 to 13%. The
      high rate of peritoneal (26-31%), controlateral pleural and pericardial
      recurrences justify the routine practice of preoperative laparoscopy and
      controlateral thoracoscopy and a pleuropneumonectomy without pericardotomy and
      diaphragmatic resection. The diaphragm is lowered to facilitate radiotherapy.
      Chemotherapy may be performed postoperatively.

PMID- 16949850
TI  - Development of an effective Japanese encephalitis virus-specific DNA vaccine.
AB  - Intramuscular immunization with DNA vaccines has been shown to induce a broad
      range of immune responses and protective immunity in many animal models, but it
      is less effective in primates. One reason for this may be the low expression of
      vector-encoded antigen in cells. Here we report that the use of vaccine vector
      (pCJ-3) containing two regulatory elements, a chimeric intron and a bovine growth
      hormone (BGH) polyadenylation signal, markedly increased antigen expression both
      in vitro and in vivo. A positive correlation was seen between the level of
      expression of Japanese encephalitis virus (JEV) envelope proteins and the levels
      of antibodies in C3H/HeN mice. Immunization of mice with pCJ-3/ME (pCJ-3
      containing the entire membrane and envelope protein genes) with or without
      cardiotoxin pretreatment resulted in higher antibody titers than immunization
      with vector containing only envelope protein and conferred full protection
      against infection with JEV. Electron microscopy showed that pCJ-3/ME expression
      resulted in the production of virus-like particles of JEV in vitro. The particles
      enhanced the production of higher titers of neutralizing antibodies and thus
      provided immunity against JEV. Consequently, the efficacy of the newly developed
      DNA vaccines was validated. This should pave the way to clinical trials in man.

PMID- 16949851
TI  - [Epigenetics of the sperm cell].
AB  - In addition to genetic information, the spermatozoon carries another type of
      information, named epigenetic, which is not associated with variations of the DNA
      sequence. In somatic cells, it is now generally admitted that epigenetic
      information is not only regulated by DNA methylation but also involves
      modifications of the genome structure, or epigenome. During male germ cell
      maturation, the epigenome is globally re-organized, since most histones, which
      are associated to DNA in somatic cells, are removed and replaced by sperm
      specific nuclear proteins, the protamines, responsible for the tight compaction
      of the sperm DNA. However, a small proportion of histones, and probably other
      proteins, are retained within the sperm nucleus, and the structure of the sperm
      genome is actually heterogeneous. This heterogeneity of the sperm epigenome could
      support an epigenetic information, transmitted to the embryo, which could be
      crucial for its development. Although it is nowadays possible to appreciate the
      global structure of the sperm genome, the precise constitution of the sperm
      epigenome remains unknown. In particular, very recent data suggest that specific
      regions of the genome could be associated with particular proteins and define
      specific structures. This structural partitioning of the sperm genome could
      convey important epigenetic information, crucial for the embryo development.

PMID- 16949852
TI  - [Endometriosis surgical treatment: It's time to listen to and warn the
      patients!].

PMID- 16949853
TI  - [Three-year outcomes of the tension-free vaginal tape procedure for treatment of
      female stress urinary incontinence with low urethral closure pressure].
AB  - OBJECTIVE: The aim of this study was to assess, with long-term outcome, the
      effectiveness of TVT for stress urinary incontinence (SUI) with low maximum
      urethral closure pressure (MUCP) and to identify predicting factors for failure
      in this case. PATIENTS AND METHODS: This is a bicentric retrospective study
      including women who underwent a TVT procedure for grade 3-SUI according to the
      Ingelman-Sundberg's scale. All patients had a low MCUP defined by PCUM < 30 or by
      the formula 110-the age+/-20% cmH2O. Urethral hypermobility was defined on
      physical examination and urodynamic investigations. TVT was the only operation
      performed. Patients were assessed at three months then at longer term with an
      average follow-up of three years and ever less than one year. RESULTS: A total of
      60 women 30 to 78 years old (mean age 55) were so operated. More than third of
      them (38%) had already been operated for incontinence. Thirty-eight percent had
      SUI without urethral hypermobility. Thirty percent presented bladder
      overactivity. The short-term evaluation found that, out of 58 patients, 70,6%
      cured, 10,3% improved and 18,9% classified as failure. The long-term evaluation,
      concerning 44 patients, found that 57% remained cured, 16% improved and 27% were
      classified as failure. Bladder overactivity was cured or improved in more than
      half of the cases (60%). Ten percent of de novo urgencies were noted, all of
      which persisted later on. For all that, as much as two thirds of these patients
      were satisfied with the TVT. Mean age of patients classified as failure, was
      higher (65 years). Previous SUI surgery did not modify the results. When the MUCP
      was < 20 cmH2O, success was present only one time out of two. The absence of
      urethral hypermobility decreased to a significant degree the probability of cure
      (38 vs. 82,6%, P < 0.01), and more still when bladder overactivity was associated
      (16,6 vs. 66,6%, P < 0.01). Postoperative voiding troubles constituted a
      pejorative factor for success of surgery. DISCUSSION AND CONCLUSION: Even if
      results of TVT with low MCUP are worse, they do not remain less appreciable. When
      we confront the benefits awaited with this technique compared to the usually
      described complications, TVT must represent the first treatment of this
      indication.

PMID- 16949854
TI  - Feasibility of a percutaneous technique for repairing proximal femora with
      simulated metastatic lesions.
AB  - Fracture of the proximal femur due to metastatic disease is a significant cause
      of morbidity and mortality among breast cancer patients. Prophylactic surgical
      fixation is advised for patients at risk of fracture and typically involves
      placement of an orthopaedic implant. We propose that some proximal femora with
      metastases can be repaired by removing the lesion and filling the resulting
      defect with bone cement (polymethylmethacrylate), a procedure that could be
      performed percutaneously without the use of hardware. We studied the strengths of
      12 matched pairs of cadaveric proximal femora under single-limb stance loading.
      One femur from each pair remained intact, while a simulated metastatic lesion,
      measuring approximately 75% of the neck diameter, was burred into the neck of the
      contralateral femur. The defects were repaired using a procedure similar to the
      one proposed. Femoral strength was measured via mechanical testing to failure.
      The strengths of the repaired femora averaged 94.7% of the strength of their
      respective contralateral intact femur (standard deviation, 8.7%). These findings
      suggest that the proposed procedure may be useful for some patients with
      metastases in the femoral neck. If the proximal femur could be safely repaired
      using the proposed technique in place of conventional surgical fixation, the
      patient would benefit from a shorter and less invasive surgical procedure, less
      pain and discomfort, greatly reduced recovery time, and a shorter hospital stay
      all at a much lower cost.

PMID- 16949856
TI  - Accumulation and bioavailability of dietary carotenoids in vegetable crops.
AB  - Carotenoids are lipid-soluble pigments found in many vegetable crops that are
      reported to have the health benefits of cancer and eye disease reduction when
      consumed in the diet. Research shows that environmental and genetic factors can
      significantly influence carotenoid concentrations in vegetable crops, and that
      changing cultural management strategies could be advantageous, resulting in
      increased vegetable carotenoid concentrations. Improvements in vegetable
      carotenoid levels have been achieved using traditional breeding methods and
      molecular transformations to stimulate biosynthetic pathways. Postharvest and
      processing activities can alter carotenoid chemistry, and ultimately affect
      bioavailability. Bioavailability data emphasize the importance of carotenoid
      enhancement in vegetable crops and the need to characterize potential changes in
      carotenoid composition during cultivation, storage and processing before consumer
      purchase.

PMID- 16949857
TI  - What if higher plants lack a CDC25 phosphatase?
AB  - Progression through the cell cycle is regulated by cyclin-dependent kinases
      (CDKs). Plants possess a unique class of CDKs, designated B-type CDKs, but seem
      to lack a functional CDC25 phosphatase, which is a crucial activator of the onset
      of mitosis in non-plant species. Based on a striking number of functional
      parallels between the Arabidopsis thaliana CDKB1;1 and the Drosophila
      melanogaster CDC25 (string), we hypothesize that the acquisition of B-type CDKs
      and the disappearance of CDC25 in plants might have been associated; in these
      coupled events, the CDC25-controlled onset of mitosis might have been
      evolutionarily replaced by a B-type CDK-dominated pathway, eventually resulting
      in the loss of the CDC25 gene.

PMID- 16949855
TI  - A multifocal electroretinogram model predicting the development of diabetic
      retinopathy.
AB  - The prevalence of diabetes has been accelerating at an alarming rate in the last
      decade; some describe it as an epidemic. Diabetic eye complications are the
      leading cause of blindness in adults aged 25-74 in the United States. Early
      diagnosis and development of effective preventatives and treatments of diabetic
      retinopathy are essential to save sight. We describe efforts to establish
      functional indicators of retinal health and predictors of diabetic retinopathy.
      These indicators and predictors will be needed as markers of the efficacy of new
      therapies. Clinical trials aimed at either prevention or early treatments will
      rely heavily on the discovery of sensitive methods to identify patients and
      retinal locations at risk, as well as to evaluate treatment effects. We report on
      recent success in revealing local functional changes of the retina with the
      multifocal electroretinogram (mfERG). This objective measure allows the
      simultaneous recording of responses from over 100 small retinal patches across
      the central 45 degrees field. We describe the sensitivity of mfERG implicit time
      measurement for revealing functional alterations of the retina in diabetes, the
      local correspondence between functional (mfERG) and structural (vascular)
      abnormalities in eyes with early nonproliferative retinopathy, and longitudinal
      studies to formulate models to predict the retinal sites of future retinopathic
      signs. A multivariate model including mfERG implicit time delays and 'person'
      risk factors achieved 86% sensitivity and 84% specificity for prediction of new
      retinopathy development over one year at specific locations in eyes with some
      retinopathy at baseline. A preliminary test of the model yielded very positive
      results. This model appears to be the first to predict, quantitatively, the
      retinal locations of new nonproliferative diabetic retinopathy development over a
      one-year period. In a separate study, the predictive power of a model was
      assessed over one- and two-year follow-ups. This permitted successful prediction
      of new retinopathy development in eyes with and without retinopathy at baseline.
      Finally, we briefly describe our current research efforts to (a) locally predict
      future sight-threatening diabetic macular edema, (b) investigate local retinal
      function change in adolescent patients with diabetes, and (c) better understand
      the physiological bases of the mfERG delays. The ability to predict the retinal
      locations of future retinopathy based on mfERG implicit time provides clinicians
      a powerful tool to screen, follow-up, and even consider early prophylactic
      treatment of the retinal tissue in diabetic patients. It also aids identification
      of 'at risk' populations for clinical trials of candidate therapies, which may
      greatly reduce their cost by decreasing the size of the needed sample and the
      duration of the trial.

PMID- 16949858
TI  - Toxicological assessment of ambient and traffic-related particulate matter: a
      review of recent studies.
AB  - Particulate air pollution (PM) is an important environmental health risk factor
      for many different diseases. This is indicated by numerous epidemiological
      studies on associations between PM exposure and occurrence of acute respiratory
      infections, lung cancer and chronic respiratory and cardiovascular diseases. The
      biological mechanisms behind these associations are not fully understood, but the
      results of in vitro toxicological research have shown that PM induces several
      types of adverse cellular effects, including cytotoxicity, mutagenicity, DNA
      damage and stimulation of proinflammatory cytokine production. Because traffic is
      an important source of PM emission, it seems obvious that traffic intensity has
      an important impact on both quantitative and qualitative aspects of ambient PM,
      including its chemical, physical and toxicological characteristics. In this
      review, the results are summarized of the most recent studies investigating
      physical and chemical characteristics of ambient and traffic-related PM in
      relation to its toxicological activity. This evaluation shows that, in general,
      the smaller PM size fractions (<PM(10)) have the highest toxicity, contain higher
      concentrations of extractable organic matter (comprising a wide spectrum of
      chemical substances), and possess a relatively high radical-generating capacity.
      Also, associations between chemical characteristics and PM toxicity tend to be
      stronger for the smaller PM size fractions. Most importantly, traffic intensity
      does not always explain local differences in PM toxicity, and these differences
      are not necessarily related to PM mass concentrations. This implies that PM
      regulatory strategies should take PM-size fractions smaller than PM(10) into
      account. Therefore, future research should aim at establishing the relationship
      between toxicity of these smaller fractions in relation to their specific
      sources.

PMID- 16949859
TI  - Study the oxidative injury of yeast cells by NADH autofluorescence.
AB  - Autofluorescence has an advantage over the extrinsic fluorescence of an
      unperturbed environment during investigation, especially in complex system such
      as biological cells and tissues. NADH is an important fluorescent substance in
      living cells. The time courses of intracellular NADH autofluorescence in the
      process of yeast cells exposed to H(2)O(2) and ONOO(-) have been recorded in
      detail in this work. In the presence of different amounts of H(2)O(2) and ONOO(
      ), necrosis, apoptosis and reversible injury are initiated in yeast cells, which
      are confirmed by acridine orange/ethidum bromide and Annexin V/propidium iodide
      staining. It is found that intracellular NADH content increases momently in the
      beginning of the apoptotic process and then decreases continually till the cell
      dies. The most remarkable difference between the apoptotic and the necrotic
      process is that the NADH content in the latter case changes much more sharply.
      Further in the case of reversible injury, the time course of intracellular NADH
      content is completely different from the above two pathways of cell death. It
      just decreases to some degree firstly and then resumes to the original level.
      Based on the role of NADH in mitochondrial respiratory chain, the time course of
      intracellular NADH content is believed to have reflected the response of
      mitochondrial redox state to oxidative stress. Thus, it is found that the
      mitochondrial redox state changes differently in different pathways of oxidative
      injury in yeast cells.

PMID- 16949860
TI  - EmerLoc: location-based services for emergency medical incidents.
AB  - BACKGROUND: Recent developments in positioning systems and telecommunications
      have provided the technology needed for the development of location aware medical
      applications. We developed a system, named EmerLoc, which is based upon this
      technology and uses a set of sensors that are attached to the patient's body, a
      micro-computing unit which is responsible for processing the sensor readings and
      a central monitoring unit, which coordinates the data flow. OBJECTIVE: To
      demonstrate that the proposed system is technically feasible and acceptable for
      the potential users. METHOD: Transmission speed is assessed mostly by means of
      transmission of DICOM compliant images in various operational scenarios. The
      positioning functionality was established both outdoor using GPS and indoor using
      the UCLA Nibble system. User acceptability was assessed in a hospital setting by
      15 physicians who filled in a questionnaire after having used the system in an
      experimental setting. RESULTS: Transmission speeds ranged from 88kB/s for a IEEE
      802.11 infrastructure to 2.5kB/s for a GSM/GPRS scenario. Positioning accuracy
      based on GPS was 5-10m. The physicians rated the technical aspects on average
      above 3 on a 5-point scale. Only the data presentation was assessed to be not
      satisfactory (2.81 on a 5-point scale). CONCLUSION: The reported results prove
      the feasibility of the proposed architecture and its alignment with widely
      established practices and standards, while the reaction of potential users who
      evaluated the system is quite positive.

PMID- 16949861
TI  - Granulocytapheresis (GCAP) for severe alcoholic hepatitis-A preliminary report.
AB  - AIM: To evaluate the efficacy of granulocytapheresis therapy in alcoholic
      hepatitis. METHODS: We attempted to trap leukocytes in the peripheral circulation
      using the granulocytapheresis (GCAP) technique in patients with severe alcoholic
      hepatitis who showed a marked elevation of peripheral leukocytes. Corticosteroids
      were co-administered. RESULTS: The Maddrey's indices for these patients varied
      between 42 and 117 and MELD scores for alcoholic hepatitis (Mayo) ranged from 20
      to 44. Survival rate was 50% (3/6), which is better than the results reported
      recently for similar patients in a national survey (29%). The effect of GCAP was
      reflected in decreases in interleukin-6 and interleukin-8 levels as well as in
      serum concentrations of soluble intercellular adhesion molecule. White blood cell
      counts were not affected. In the surviving patients, the Maddrey's indices and
      MELD scores for alcoholic hepatitis varied between 49 and 67, and 20 and 22,
      respectively, showing that GCAP is effective in patients with disease of moderate
      severity. Hemolytic anemia occurred in one patient after GCAP therapy. Other
      events such as pancreatitis, pneumonia, and cerebral hemorrhage were considered
      to be related to the alcoholic hepatitis itself. CONCLUSION: GCAP therapy
      deserves further evaluation as a new therapeutic modality for a moderately severe
      alcoholic hepatitis.

PMID- 16949862
TI  - Novel mutations in the respiratory syncytial virus G gene identified in viral
      isolates from a girl with severe combined immune deficiency treated with
      intravenous immune globulin.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) can cause prolonged infections in
      individuals with compromised immunity. OBJECTIVES: To investigate whether RSV
      evolves during prolonged infection in an immunocompromised host. STUDY DESIGN: We
      sequenced the envalope glycoprotein genes of RSV obtained at three time points
      during a 59-day period from a 4-year-old female with severe combined immune
      deficiency (SCID) treated with intravenous immunoglobulin (IVIG). RESULTS:
      Sporadic silent mutations were found in the SH, G and F genes among three RSV
      samples collected at days 0, 19 and 59. Premature stop codons at amino acid
      positions 257 and 278 were present in the RSV G glycoprotein gene sequenced from
      each time point. None of the 48 RSV G sequences available on GenBank or any of 50
      genetically diverse clinical isolates of RSV contained these mutations. These
      premature stop codon mutations occurred at the same positions of the G
      glycoprotein gene as those described in in vitro monoclonal-antibody resistant
      mutants reported elsewhere. CONCLUSION: Our patient was most likely infected with
      a single RSV strain that did not mutate during the study period. This strain
      contains unique mutations that may have previously evolved in this individual who
      had prolonged infection and was treated with monthly IVIG.

PMID- 16949863
TI  - Characteristics of electrical activity in trapezius muscles with myofascial pain.
AB  - OBJECTIVE: To study the reliability and validity of resting electrical activity
      from tender areas in muscle. METHODS: In seven subjects with tender areas in
      their trapezius muscles, electromyographic (EMG) signals were obtained from
      monopolar needles at various depths over the tender area and at the same depths
      over the control area, and from surface electrodes. At selected depths, multiple
      epochs were recorded. RESULTS: Increased electrical activity occurred from the
      electrode inserted toward the tender area in all seven subjects (to a mean of
      47.6 microV), but not from control areas. The depths of the maximal EMG
      amplitudes advancing and withdrawing the needle were usually within 3 mm. The EMG
      amplitude from the first of multiple epochs (38.4 microV) did not differ from the
      average (40.0 microV) of subsequent epochs (paired-t test, 6 df, 0.2<p<0.3).
      CONCLUSIONS: We suggest that the electrical activity arises from a localized zone
      and is stable over time. SIGNIFICANCE: Our data provide evidence for the
      reliability and validity of the electrical activity from myofascial tender areas.

PMID- 16949865
TI  - Abnormal brainstem auditory evoked responses in mitochondrial
      neurogastrointestinal encephalomyopathy (MNGIE): evidence of delayed central
      conduction time.
AB  - OBJECTIVE: To assess the usefulness of brain auditory evoked potentials (BAEPs)
      in the study of asymptomatic white matter alterations in brain MRI observed in
      mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) patients. METHODS:
      The authors studied the neurophysiological characteristics of the BAEPs in four
      genetically confirmed MNGIE patients who presented varying degrees of
      leukoencephalopathy in brain MRI. RESULTS: Prolonged I-III and I-V interpeak
      latencies were the most common abnormalities found, with a correlation between
      the extent of brain MRI lesions and BAEPs. CONCLUSIONS: The findings suggest a
      delayed central conduction time along the brainstem. BAEPs may be useful in the
      neurophysiological evaluation of central white matter lesions in MNGIE. Similar
      neurophysiological findings have been reported in other myelin disorders in the
      central nervous system. SIGNIFICANCE: The BAEPs abnormalities identified should
      be interpreted as an indirect sign of CNS involvement in MNGIE patients and
      provide comprehensive and integrated information concerning brainstem
      dysfunction. Further studies are necessary in order to identify whether there is
      a correlation between BAEPs and the clinical progression of the disease.

PMID- 16949866
TI  - Catabolite repression of the SirA regulatory cascade in Salmonella enterica.
AB  - Orthologs of the Salmonella BarA/SirA two-component system are required for
      virulence, motility, secondary metabolism and stress survival throughout the
      gamma-proteobacteria. BarA is a sensor kinase that responds to an unknown signal
      by phosphorylating the response regulator SirA. SirA increases the expression of
      genes within Salmonella pathogenicity island 1 (SPI1) that encode a type III
      secretion system (TTSS-1). SirA does this by directly activating the hilA and
      hilC regulatory genes encoded within SPI1. SirA also directly activates the csrB
      regulatory RNA gene. This RNA antagonizes the activity of the post
      transcriptional regulatory protein CsrA that binds the mRNA of its targets to
      regulate SPI1, motility and secondary metabolism. A second regulatory RNA, csrC,
      is also strongly regulated by SirA, although gel mobility shift assays do not
      demonstrate a direct interaction. Additionally, we have determined that the sirA
      gene is activated by crp and cya. The effects of crp and cya were also observed
      on the downstream members of the SirA regulon, hilA, sopB, csrB, and csrC.
      However, gel mobility shift experiments and DNA sequence analysis suggest that
      the regulation of sirA by CRP is probably indirect. Although SirA does not
      regulate csrA, this gene was also under crp/cya control. Supplementation of a
      rich medium with phosphate diminished the catabolite control of the csr portion
      but not the virulence portion of the SirA regulon.

PMID- 16949867
TI  - Foot morphology and foot/ankle injury in indoor football.
AB  - While the pronated foot is implicated as a risk factor for sports injury in some
      studies, others suggest that a supinated foot posture increases the risk of
      overuse lower limb injuries. Athletes in a given sports discipline may tend to
      have a similar foot morphology, which varies from that observed elsewhere.
      Further, the foot morphology that is beneficial for performance in a sport may be
      detrimental with regard to injury. Intra- and inter-rater reliability of the Foot
      Posture Index (FPI-6) as a measure of foot morphology was determined (ICC (2,1)
      0.88 and 0.69 respectively). Thereafter, in a prospective cohort study using the
      FPI-6, 76 adolescent male indoor football (Futsal) players were measured and
      followed monthly over one competition season. Coach-rated ability and reports of
      any overuse injuries at the ankle and/or foot over this period were obtained. A
      significant negative linear relationship was found between the mean FPI-6 scores
      and coach-rated ability (p=0.008), with supinated and under-pronated postures
      related to higher ability level. Overall, 33% of injuries at the ankle and/or
      foot were classified as overuse. Foot Posture Index scores of less than 2,
      indicating the supinated and under-pronated feet, were found to be associated
      with a significant increase in the risk of overuse injury (p=0.008). The greater
      rigidity of these foot types may assist adolescent, male, indoor football players
      to perform at a higher level in their sport. Unfortunately, these players are
      also more likely to sustain ankle and/or foot overuse injuries.

PMID- 16949868
TI  - Reproducibility of a 6-s maximal cycling sprint test.
AB  - The purpose of this study was to examine the reproducibility in measures of power
      output during a 6-s, maximal cycling sprint test. Eleven healthy, moderately
      trained males (mean+/-S.D.; age=19+/-1 year; height=181.5+/-6.2 cm; mass=76.9+/
      9.5 kg; peak oxygen uptake 54.9+/-6.1 mL kg(-1)min(-1)) performed a 6-s standing
      sprint on a front-access cycle ergometer on four separate occasions. Peak power
      output (PPO) was significantly higher (4.9%; P<0.05) in trial 2 compared with
      trial 1, whereas there were no significant differences between trials 2, 3 and 4.
      Similarly, the mean power output (MPO) for trial 2 was higher (5.8%; P<0.05) than
      in trial 1, but there were no difference across trials 2, 3 and 4. The within
      subject coefficient of variation (CV) from trials 2 to 4 was 2.8 and 2.9% for PPO
      and MPO, respectively, while the CV calculated using data from the third and
      fourth trial was lower: 1.8 and 2.5% for PPO and MPO, respectively. The results
      of the study showed that reliable power outputs can be obtained after one
      familiarization session in subjects unfamiliar with maximal cycling sprint
      exercise. However, the inclusion of an extra familiarization session ensured more
      stable power outputs. Therefore, two trials should allow adequate familiarization
      with the maximal 6-s cycling test.

PMID- 16949869
TI  - Reducing the risk of heat-related decrements to physical activity in young
      people.
AB  - The purpose of this review is to highlight differences in thermoregulatory
      responses during activity of children and adolescents compared with adults. Some
      differences are due to movement inefficiency and physical size such as body
      surface area to body mass ratio, and body composition. Identified physiological
      differences in sweat rates appear to alter with maturation, at least in boys, but
      the research remains incomplete. A number of findings from hydration studies with
      young people exercising in the heat are also discussed. The research on clothing
      is adult-based, but key concepts from this research also apply to children. The
      final section addresses the limited research on acclimatization of children to
      hot conditions. Specific recommendations for children who are active in the heat
      conclude this review.

PMID- 16949870
TI  - Protein carbonyls are acutely elevated following single set anaerobic exercise in
      resistance trained men.
AB  - The purpose of this investigation was to determine if a single set of strenuous
      squat exercise would result in an acute oxidative stress, as demonstrated
      previously by a single sprint. Thirteen resistance trained men performed one set
      of 15 repetitions of barbell squats using 70% of one repetition maximum and a 30
      s maximal cycle sprint on two different occasions. The total work performed was
      calculated for each exercise bout. Heart rate, perceived exertion, blood lactate,
      protein carbonyls, 8-hydroxydeoxyguanosine, and malondialdehyde were measured
      before and within 1 min following exercise. No differences were noted between the
      squat and sprint tests for total work, heart rate or perceived exertion. An
      exercise test by time interaction was evident for blood lactate with values
      greater following sprinting compared to squatting (P=0.0005). Postexercise
      protein carbonyls were not different between exercise tests but were elevated
      above rest (P=0.04) by 111% and 74% following sprinting and squatting,
      respectively, while 8-hydroxydeoxyguanosine and malondialdehyde were relatively
      unaffected by either exercise test. These data indicate that a single bout of
      strenuous squatting and sprinting performed by resistance trained men results in
      elevated protein carbonyls, while having little impact on 8-hydroxydeoxyguanosine
      or malondialdehyde during the immediate postexercise period.

PMID- 16949871
TI  - Pharmacotherapy for functional gastrointestinal disorders in children.
AB  - Functional gastrointestinal disorders are among the most common medical problems
      in pediatrics. However, only a few well-designed trials have evaluated the
      efficacy and safety of treatments in these conditions. Data obtained from studies
      conducted in adults are often utilized to tailor treatment to children with
      functional gastrointestinal disorders. This practice might lead to substantial
      medication under- or over-dosing, or use of drugs for an incorrect indication.

PMID- 16949872
TI  - Germinal-centre reactions in allergic inflammation.
AB  - Primary and secondary immune responses in the germinal centres of lymphoid organs
      have been studied in the past. There is now compelling evidence of a third stage
      in the immune response, in 'tertiary lymphoid organs' that develop at sites of
      chronic inflammation in response to persistent local antigen challenge. Germinal
      centre-like reactions are well-documented in the target organs of autoimmune
      diseases. Here, we review recent evidence that they also occur at sites of
      allergic inflammation.

PMID- 16949873
TI  - Neural responses associated with positive and negative emotion processing in
      patients with left versus right temporal lobe epilepsy.
AB  - Studies on emotion processing in patients with temporal lobe epilepsy have dealt
      mainly with the processing of negative emotions. To further understand the neural
      basis of emotional disorders in temporal lobe epilepsy, we studied patterns of
      brain activation induced by implicit processing of negative and positive emotions
      perceived through facial expressions and emotionally salient stimuli in
      candidates for surgical treatment of intractable epilepsy. Using functional MRI,
      we compared, in patients with mesial temporal lobe epilepsy and healthy subjects,
      the patterns of brain activation elicited by the implicit processing of fearful,
      sad, and happy faces and pleasant and unpleasant scenes. The results revealed
      different patterns of activation in patients with left and right mesial temporal
      lobe epilepsy, compared with healthy subjects, suggesting that the left and right
      mesial temporal regions are involved differently in emotion processing, which
      could be related to different contributions in emotional arousal.

PMID- 16949875
TI  - Peripheral formalin injection induces long-lasting increases in cyclooxygenase 1
      expression by microglia in the spinal cord.
AB  - Activated glia are a source of substances known to enhance pain, including
      centrally synthesized prostaglandins. We have previously shown that microglia are
      activated in the spinal cord following peripheral formalin injection. In the
      present study, we investigated cyclooxygenase (COX-1 and COX-2) expression in the
      spinal cord using immunohistochemistry and Western blots in the formalin pain
      model, to further understand how spinal glia modulate pain processing. We show
      that both COX-1 and COX-2 are constitutively expressed in the spinal cord. Hind
      paw formalin injection increased COX-1 expression, beginning at 1 day after
      injection and lasting at least 2 weeks, the duration of experiments. The COX-2
      expression changed considerably less, with a significant increase of COX-2
      protein level only observed at 2 h after injection. Double labeling studies
      showed that COX-1 was expressed in microglia and COX-2 was expressed in neurons.
      These data indicate that both COX-1 and COX-2 are increased in the spinal cord
      following formalin injection, but the time course and cellular sources are
      different, suggesting that both COX-1 (longer time points) and COX-2 (very short
      time points) may be involved in spinal modulation in the formalin pain model. Our
      study also suggests that spinal microglial activation may play a role in long
      term hyperalgesia through the increased expression of COX-1. PERSPECTIVE: This
      article reports that COX-1 expression by microglia is increased in the spinal
      cord after peripheral formalin injection into the rat hind paw. This result could
      potentially help clinicians understand how COX-1 may be involved in pain
      processing and the role microglial activation plays in pain mechanisms.

PMID- 16949874
TI  - Pain in aging community-dwelling adults in the United States: non-Hispanic
      whites, non-Hispanic blacks, and Hispanics.
AB  - Racial and ethnic disparities in healthcare persist in the U.S. Although pain is
      one of the most prevalent and disabling symptoms of disease, only a few studies
      have assessed disparities in pain in large racially and ethnically diverse,
      middle- to late aged community samples, thus limiting the generalizability of
      study findings in broader populations. With data from the 2000 Health and
      Retirement Study, we assessed the prevalence and impact of pain in a community
      sample of aging (> or =51 years old) non-Hispanic whites (n = 11,021), non
      Hispanic blacks (n = 1,804), and Hispanics (n = 952) in the U.S. Pain, pain
      severity, activity limitation as a result of pain, comorbid conditions, and
      sociodemographic variables were assessed. Results showed that pain prevalence was
      28%, and 17% of the sample reported activity limitation as a result of pain. Non
      Hispanic blacks (odds ratio [OR], 1.78; 99% confidence interval [CI], 1.33-2.37)
      and Hispanics (OR, 1.80; 99% CI, 1.26-2.56) had higher risk for severe pain
      compared with non-Hispanic whites. Analyses of respondents with pain (n = 3,811)
      showed that having chronic diseases (2 comorbid conditions, OR, 1.5; 99% CI, 1.09
      2.17), psychological distress (OR, 1.99; 99% CI, 1.54-2.43), being a Medicaid
      recipient (OR, 1.63; 99% CI, 1.17-2.25), and lower educational level (OR, 1.45;
      99% CI, 1.14-1.85) were significant predictors for severe pain and helped to
      explain racial/ethnic differences in pain severity. PERSPECTIVE: This study,
      which used a large racially and ethnically diverse community sample, provided
      empirical evidence that racial/ethnic difference in pain severity in aging
      community adults in the U.S. can be accounted for by differential vulnerability
      in terms of chronic disease, socioeconomic conditions, and access to care.

PMID- 16949876
TI  - Preamputation pain and acute pain predict chronic pain after lower extremity
      amputation.
AB  - Although previous research suggests that preamputation pain is a risk factor for
      pain after amputation, little is known about the association between acute
      postsurgical pain and chronic amputation-related pain. The current prospective
      study examined the associations of preamputation pain and acute postamputation
      pain with chronic amputation-related pain. The sample consisted of patients with
      lower limb amputation (N = 57) who provided both preamputation and postamputation
      data during a 2-year study period. Preamputation pain intensity and duration were
      assessed before amputation; acute phantom limb pain (PLP) and residual limb pain
      (RLP) intensity were assessed on postsurgical days 4 and 5. Acute PLP intensity
      was the only significant independent predictor of chronic PLP intensity at 6 and
      12 months after amputation, whereas preamputation pain intensity was the only
      significant predictor of chronic PLP intensity at 24 months. Similarly, acute RLP
      was found to be the best overall predictor of chronic RLP. Other variables (age,
      gender, level and etiology of amputation, amount of postsurgical pain medication,
      and duration of preamputation pain) were not associated with chronic pain. These
      results suggest that higher levels of pain either before or soon after amputation
      might help to identify individuals at greatest risk for chronic pain problems and
      most in need of early, intensive pain interventions. PERSPECTIVE: This study
      suggests that both preamputation pain and acute pain soon after amputation might
      be associated with bothersome chronic pain. The results support further research
      on acute pain mechanisms and the effectiveness of early interventions aimed at
      preventing or managing amputation-related pain.

PMID- 16949877
TI  - Effects of prolonged wrist flexion on transmission of sensory information in
      carpal tunnel syndrome.
AB  - Carpal tunnel syndrome presents a constellation of symptoms which include
      discomfort (eg, pain, paraesthesia) and diminished sense of touch. This
      exploratory study simultaneously measured changes in tactile threshold and
      discomfort ratings during prolonged wrist flexion in symptomatic patients from a
      rehabilitation clinic and from a control population. Prolonged (15 min) wrist
      flexion significantly increased tactile threshold and discomfort ratings above
      baseline levels in both symptomatic and control populations. Sixty-two percent of
      the symptomatic sample was found to have abnormal conduction latency. Tactile
      threshold in symptomatic subjects with normal conduction latency (n = 13) did not
      differ significantly from control subjects (n = 36) at baseline but showed
      significant elevation during wrist flexion. In contrast, subjects with abnormal
      conduction latency (n = 21) exhibited significant elevation relative to control
      subjects at baseline and throughout wrist flexion as well as a slower recovery
      after flexion. Conduction latency correlated with baseline (r = .52, P < .0001)
      and 15-min (r = .67, P < .0001) tactile threshold for the entire subject
      population, as well as 15-min threshold (r = .53, P = .013) for the subpopulation
      with abnormal conduction latency. At 2.5 min after flexion, correlation was
      significant for whole (r = .64, P < .0001) and abnormal conduction latency (r =
      .58, P = .0063) samples. Regression slope of tactile threshold versus conduction
      latency was significantly greater than zero and did not differ significantly from
      linearity. The study demonstrates that increases in mechanosensory threshold and
      discomfort ratings during prolonged wrist flexion are more profound (and recovery
      less rapid) in patients with electrophysiologic evidence of injury. PERSPECTIVE:
      This study demonstrates a provocative procedure that enhances the symptoms of
      carpal tunnel syndrome. This measure may help clinicians discriminate median
      nerve compression from other types of peripheral nerve injury and help
      researchers investigate the impact of mechanical stress, tissue compression, and
      vascular stasis on compression-related neuropathy.

PMID- 16949878
TI  - Symptom profiles differ in patients with neuropathic versus non-neuropathic pain.
AB  - The distinction between neuropathic and non-neuropathic pain reflects partially
      distinct mechanisms and patterns of treatment response. It was therefore
      hypothesized that patients with neuropathic and non-neuropathic pain have
      different profiles of symptoms and signs. To test this hypothesis, pain
      intensity, unpleasantness, quality, and spatial characteristics were examined in
      618 patients with 1 of 3 peripheral neuropathic pain conditions (painful diabetic
      peripheral neuropathy, painful idiopathic sensory polyneuropathy, or postherpetic
      neuralgia), osteoarthritis pain, or low back pain. These assessments were
      conducted before treatment had begun in clinical trials of lidocaine patch 5%
      administered alone or with stable dosages of other analgesics. Patients with
      osteoarthritis pain and low back pain did not differ in their profile of pain
      quality and spatial characteristics and were combined to form a group of patients
      with non-neuropathic pain. In univariate analyses, patients with peripheral
      neuropathic pain reported significantly more intense hot, cold, sensitive, itchy,
      and surface pain and significantly less intense dull and deep pain than patients
      with non-neuropathic pain. In a multivariate analysis, the overall pattern of
      pain quality and spatial characteristics differed significantly between patients
      with neuropathic and non-neuropathic pain. In addition, specific pain quality and
      spatial characteristics improved the discrimination of patients with neuropathic
      and non-neuropathic pain in a logistic regression model that adjusted for
      demographic covariates and overall pain intensity and unpleasantness.
      PERSPECTIVE: The results indicate that the distinction between neuropathic and
      non-neuropathic pain is reflected in different profiles of pain quality and
      spatial characteristics and suggest that the assessment of patterns of pain
      symptoms might contribute to the identification of distinct pathophysiologic
      mechanisms and the development of mechanism-based treatment approaches.

PMID- 16949879
TI  - The EVMS pain education initiative: a multifaceted approach to resident
      education.
AB  - Chronic pain is a major health issue that causes significant patient morbidity as
      well as economic loss. Many studies have highlighted the lack of training in
      chronic pain management for resident physicians and the need to develop programs
      that address the challenges of providing care to chronic pain patients. We wanted
      to determine whether a workshop using a combination of standardized patients,
      small groups, and large group lectures addresses residents' curricular needs
      regarding chronic pain management. We developed a 1-day workshop for residents at
      Eastern Virginia Medical School, which has a nationally recognized professional
      skills center. After completing the workshop, residents showed significant gains
      in knowledge (post-test vs pre-test overall mean +23.4%, P < .001). Significant
      gains in clinical skills were also seen (overall +5.9%, P < .001) with
      improvements in the areas of pain assessment (+6.3%, P < .001), physical
      examination (+7.7%, P < .03), and pain management (+8%, P < .01). Physicians also
      reported increased comfort regarding chronic pain management. Almost all
      residents stated they would make specific practice changes in the assessment and
      management of chronic pain patients. The results suggest our workshop is a novel
      model that is effective in teaching residents how to assess and manage chronic
      pain. PERSPECTIVE: This article demonstrates that the use of standardized
      patients with other teaching methods is an effective approach in teaching
      resident physicians regarding the assessment and management of chronic pain
      patients. The findings have the potential to restructure our methods of teaching
      in chronic pain education.

PMID- 16949880
TI  - Cytokine profiles during carrageenan-induced inflammatory hyperalgesia in rat
      muscle and hind paw.
AB  - It is not known if a cytokine cascade develops during muscle inflammation and
      whether cytokines contribute to muscle inflammatory pain. We measured plasma and
      tissue cytokine concentrations, and behavioral responses to noxious mechanical
      stimuli, after inducing inflammation in the gastrocnemius muscle and the hind paw
      of rats. Tissue and plasma samples were taken 3, 6, or 24 h after carrageenan or
      saline injection into one of the 2 sites. Tumor necrosis factor alpha (TNF
      alpha), interleukin (IL)-1beta, IL-6, and cytokine-induced neutrophil
      chemoattractant 1 (CINC-1) concentrations were measured. Hyperalgesia was present
      3 h after carrageenan injection into the hind paw and muscle. The TNF-alpha was
      elevated significantly in the inflamed hind paw tissue (P < .001) but not in
      inflamed muscle tissue. IL-1beta was elevated 6 h after carrageenan injection in
      the hind paw tissue but only 24 h in the muscle tissue (P < .001). The IL-6 was
      elevated 3 h after injection in the hind paw tissue but only after 6 h in the
      muscle tissue (P < .01). The CINC-1 in plasma, muscle, and hind paw was elevated
      from 3 h to 24 h after carrageenan injection (P < .01). The release of IL-1beta
      and IL-6, known to mediate hyperalgesia elsewhere, is delayed in muscle
      inflammation compared with cutaneous inflammation, whereas TNF-alpha is not
      elevated during muscle inflammation. PERSPECTIVE: The quality and mechanisms of
      muscle pain are different from that of cutaneous pain. So too is the pattern of
      cytokine release during inflammation. Inhibiting TNF-alpha is unlikely to be
      effective in managing inflammatory muscle pain, but other cytokines, notably IL
      1beta and CINC-1, may prove useful therapeutic targets.

PMID- 16949881
TI  - Lactate concentrations in incisions indicate ischemic-like conditions may
      contribute to postoperative pain.
AB  - The substances in wounds that cause incisional pain and hyperalgesia after
      surgery are poorly understood. We have developed and characterized rat models for
      incision-induced pain behaviors and measured increased tissue hydrogen ion
      concentration. Because lactate may facilitate nociceptor responses to low pH and
      contribute to ischemic pain mechanisms, we measured tissue lactate after incision
      of the plantar region of the hindpaw, gastrocnemius muscle, and paraspinal region
      in halothane anesthetized rats using in vivo microdialysis. Incisions were
      performed at 1 site (plantar, gastrocnemius, or paraspinal incision) in each rat.
      The corresponding contralateral side was used as the control. In anesthetized
      rats, a microdialysis fiber was passed into the incision and the control side. L
      Lactate was measured using the lactate oxidase method. Tissue concentration was
      determined from postoperative day 0 to postoperative day 14 using the no net flux
      method. Lactate was increased on the day of hindpaw incision to 3.6 +/- 1.6
      mmol/L compared with control (2.1 +/- .6 mmol/L) and remained increased through 7
      days. In the gastrocnemius muscle, lactate was increased the day after incision
      (4.2 +/- 1.2 mmol/L vs 1.7 +/- .5 mmol/L) until postoperative day 7. On the day
      of the paraspinal incision, lactate was 3.4 +/- 1.1 mmol/L on the operated side
      and 2.2 +/- .6 mmol/L in the control side. Lactate remained increased through
      postoperative day 8 at the paraspinal incision. These experiments demonstrate
      that incision of the plantar hindpaw, the gastrocnemius muscle, and the
      paraspinal region increased tissue lactate concentration. The wound environment
      contains increased lactate at the same time that pH is decreased; lactate could
      potentially facilitate nociceptor activation by low pH and contribute to pain
      after surgery. PERSPECTIVE: This study demonstrates that lactate is increased in
      wounds when pain behaviors and acid are increased. Lactate and low pH are present
      in incisions and indicate an ischemic pain mechanism that may contribute to
      postsurgical pain.

PMID- 16949882
TI  - Parental reassurance and pediatric procedural pain: a linguistic description.
AB  - Certain parental behaviors are associated with child coping and others with child
      distress when children undergo painful medical procedures. The finding that
      parental reassurance is linked with increases in child distress is perplexing and
      counterintuitive. The objective of the present study was to provide a detailed
      linguistic description of the speech functions and tones parents use when
      reassuring during painful medical procedures. Videotapes of 28 5-year-old
      children (12 boys, 16 girls) receiving immunizations who were accompanied by
      their parents were examined. The majority of reassuring verbalizations were
      statements; minor clauses (eg, "okay") were the next most frequent type of
      utterance. Half of the reassuring verbalizations were spoken with a falling tone,
      which is indicative of speaker certainty and protectiveness. This detailed
      linguistic approach offers new insights into the qualities of parental
      reassurance during painful medical procedures. Further research is needed to
      elucidate the complex interactions of tone, speech function, and reassurance and
      their effects on child distress. PERSPECTIVE: This article presents a detailed
      description of parental reassurance during pediatric immunizations. The
      description of the linguistic qualities of reassurance can help inform future
      research examining which characteristics of reassurance are associated with child
      distress and can help guide parental behavior during immunizations.

PMID- 16949883
TI  - Characterization of CYP1A enzyme in Adelie penguin liver.
AB  - As CYP1A enzymes are induced by certain contaminants, their induction pattern has
      been used as a biomarker for exposure of certain pollutants. Ethoxyresorufin O
      deethylase (EROD) activities are widely used in environmental assessments of
      polychlorinated biphenyls in many wildlife species. The EROD activity, a typical
      probe for CYP1A enzyme was studied in liver microsomes prepared from Adelie
      penguins (Pygoscelis adeliae) (n=10). Penguin liver microsomes (0.5 mg/mL) were
      incubated with the substrate ethoxyresorufin and NADPH at 37 degrees C for 10
      min, and the reaction was terminated by addition of methanol. The formation of
      the metabolite resorufin was assayed by an HPLC method. EROD activity was present
      in all liver samples studied. Penguin liver microsomal fraction exhibits typical
      Michaelis-Menten kinetics in the O-deethylation of ethoxyresorufin. The data were
      best described by a biphasic kinetic model, which could be interpreted in terms
      of two populations of CYP enzyme. Mean (+/-S.D.) K(m) values for high- and low
      affinity components of EROD were 51+/-109 (range: 0.16 to 358) and 872+/-703
      (range: 303 to 2450) nM, respectively. The corresponding mean V(max) values for
      the high- and low-affinity enzyme activities were 1.8+/-1.4 (range: 0.21 to 5.1)
      and 9.6+/-3.7 (range: 6.0 to 18.3) pmol/min/mg. The EROD activity in penguin
      liver microsomes was inhibited by CYP1A inhibitors (phenacetin, 7-ethoxycoumarin
      and proportional variant-naphthoflavone), whereas other CYP inhibitors for CYP2C9
      (tolbutamide), 2C19 (mephenytoin), 2D6 (debrisoquin) and 2E1
      (diethyldithiocarbamate) had no effect. These results suggest that CYP1A-like
      enzymes are present in penguin livers. The activity of this enzyme may be a
      useful biomarker for assessing the environmental impact of pollutants on
      Antarctic wildlife.

PMID- 16949885
TI  - Pavlovian conditioning of nausea and vomiting.
AB  - Cancer patients undergoing cytotoxic drug treatment often experience side
      effects, the most distressing being nausea and vomiting. Despite antiemetic
      drugs, 25-30% of the chemotherapy patients report these side-effects when being
      re-exposed to the stimuli that usually signal the chemotherapy session and its
      drug infusion. These symptoms are called anticipatory nausea and anticipatory
      vomiting. The present paper summarizes the evidence that anticipatory vomiting is
      acquired by Pavlovian conditioning, and, consequently, may be alleviated by
      conditioning techniques. To explore the mechanisms that induce and alleviate
      conditioned nausea and vomiting further, a conditioned nausea model was
      established in healthy humans using body rotation as the nausea-inducing
      treatment. The validity of this motion sickness model to examine conditioning
      mechanisms in the acquisition and alleviation of conditioned nausea was
      demonstrated. Cortisol and tumor-necrosis factor-alpha were elevated as endocrine
      and immunological correlates of nausea. Data in the rotation-induced motion
      sickness model indicated that gender is an important moderator variable to be
      considered in further studies. The paper concludes with a review of applications
      of the demonstrated conditioning principles as interventions to ameliorate
      distressing anticipatory nausea or anticipatory vomiting in cancer patients
      undergoing chemotherapy.

PMID- 16949884
TI  - Pravastatin reverses the down-regulating effect of inflammation on beta
      adrenergic receptors: a disease-drug interaction between inflammation,
      pravastatin, and propranolol.
AB  - Inflammatory conditions reduce the potency to prolong the PR interval of certain
      cardiovascular drugs including propranolol, sotalol, and verapamil in rats and
      humans despite elevated plasma drug concentrations. We tested whether pravastatin
      restores altered action and disposition of propranolol as well as inflammatory
      mediators concentrations in the Pre-Adjuvant Arthritis (Pre-AA) Sprague-Dawley
      rat model. Rats [Healthy/Placebo, Arthritis/Placebo, Healthy/Statin, and
      Arthritis/Statin groups (n=14-16/group)] received Mycobacterium butyricum on day
      0 followed by 6 mg/kg pravastatin or placebo twice daily during days 4-8. PR
      interval response to 25 mg/kg oral propranolol was measured on days 0, 4 and 8.
      On day 8, blood samples were collected for interferon-gamma, interleukin-10, C
      reactive protein, and nitrite measurements. Propranolol enantiomer
      pharmacokinetics were delineated using another 4 groups (healthy n=5, Pre-AA n=9)
      on day 8. Pre-AA significantly reduced propranolol response despite a 10-fold
      increase in concentrations. Pravastatin restored the response but not the drug
      concentrations. Area under the % effect-time curve (% min) was 714+/-214 in
      Healthy/Placebo, 256+/-249 in Arthritis/Placebo, 1534+/-367 in Healthy/Statin,
      and 1713+/-393 in Arthritis/Statin. While pravastatin reduced elevated serum
      interferon-gamma concentration in the Pre-AA model, it did not influence other
      biomarkers. Pravastatin restores response to propranolol in inflamed rat but has
      no effect on the elevated propranolol concentrations. This was associated with
      lower serum interferon-gamma concentrations.

PMID- 16949886
TI  - Identification of FGF-dependent genes in the Drosophila tracheal system.
AB  - The embryonic development of the tracheal system of the fruit fly Drosophila
      provides a paradigm for genetic studies of branching morphogenesis. Efforts of
      many laboratories have identified Branchless (Bnl, a fibroblast growth factor
      homologue) and Breathless (Btl, the receptor homologue) as crucial factors at
      many stages of tracheal system development. The downstream targets of the Bnl/Btl
      signalling cascade, however, remain mostly unknown. Misexpression of the bnl gene
      results in specific tracheal phenotypes that lead to larval death. We
      characterised the transcriptional profiles of targeted over-expression of bnl in
      the embryonic trachea and of loss-of-function bnl(P1) mutant embryos. Gene
      expression data was mapped to high-throughput in situ hybridisation based ImaGO
      annotation. Thus, we identified and confirmed by quantitative PCR 13 Bnl
      dependent genes that are expressed in cells within and outside of the tracheal
      system.

PMID- 16949887
TI  - Electrochemical screening of anti-microbial peptide LL-37 interaction with
      phospholipids.
AB  - LL-37 is an alpha-helical antimicrobial peptide of human origin. It is a 37
      residue cathelicidin peptide. This paper explores the use of electrochemical
      methods to investigate the interaction of LL-37 with phospholipid and lipid A
      monolayers on a mercury drop electrode. Experiments were carried out in
      Dulbecco's phosphate buffered saline at pH approximately 7.6. The capacity
      potential curves of the coated electrode in the presence and absence of LL-37
      were measured using out-of-phase ac voltammetry. The frequency dependence of the
      complex impedance of the coated electrode in the presence and absence of LL-37
      was estimated at -0.4 V versus Ag/AgCl 3.5 mol dm(-3) KCl. The monolayer
      permeability to ions was studied by following the reduction of Tl(I) to Tl(Hg) at
      the coated electrode. LL-37 shows no significant interaction with DOPC. However,
      LL-37 shows a small interaction with DOPG and lipid A within a DOPC monolayer
      where the monolayer permeability is marginally increased and the zero frequency
      capacitance (ZFC) is marginally decreased in both cases. LL-37 shows a
      significant interaction with a lipid A monolayer thereby decreasing the ZFC by
      30%. The results concur with the known membrane active properties of LL-37 and
      establish this electrochemical approach as a key technique for screening
      peptides.

PMID- 16949888
TI  - Neuroprotective effects of cognitive enrichment.
AB  - Cognitive enrichment early in life, as indicated by level of education,
      complexity of work environment or nature of leisure activities, appears to
      protect against the development of age-associated cognitive decline and also
      dementia. These effects are more robust for measures of crystallized intelligence
      than for measures of fluid intelligence and depend on the ability of the brain to
      compensate for pathological changes associated with aging. This compensatory
      ability is referred to as cognitive reserve. The cognitive reserve hypothesis
      suggests that cognitive enrichment promotes utilization of available functions.
      Alternatively, late life cognitive changes in cognition may be linked to a
      factor, such as cholinergic dysfunction, that is also present early in life and
      contributes to the reduced levels of early life cognitive enrichment. Beneficial
      effects of environmental enrichment early in life have also been observed in
      rodents and primates. Research with rodents indicates that these changes have
      structural correlates, which likely include increased synapses in specific brain
      regions. Dogs also show age-dependent cognitive decline, and both longitudinal
      and cross-sectional studies indicate that this decline can be attenuated by
      cognitive enrichment. Furthermore, cognitive enrichment has differential effects,
      improving some functions more than others. From a neurobiological perspective,
      behavioral enrichment in the dog may act to promote neurogenesis later in life.
      This can be distinguished from nutritional interventions with antioxidants, which
      appear to attenuate the development of neuropathology. These results suggest that
      a combination of behavioral and nutritional or pharmacological interventions may
      be optimal for reducing the rate of age-dependent cognitive decline.

PMID- 16949889
TI  - Simultaneous determination of 5-hydroxyindoleacetic acid and 5-hydroxytryptamine
      in urine samples from patients with acute appendicitis by liquid chromatography
      using poly(bromophenol blue) film modified electrode.
AB  - The fabrication and application of a novel electrochemical detection (ED) system
      with a poly(bromophenol blue) (PBPB) film chemically modified electrode (CME) for
      high performance liquid chromatography (HPLC) were described. The electrochemical
      behaviors of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA)
      at this CME were investigated by cyclic voltammetry (CV) and differential pulse
      voltammetry (DPV). It was found that the PBPB CME efficiently exhibited
      electrocatalytic effect on the current responses of 5-HT and 5-HIAA with
      relatively high sensitivity, stability and long life of activity. In HPLC-ED, the
      two analytes had good and stable current responses at the CME and their linear
      ranges were over four orders of magnitude (R> or =0.9992) with the detection
      limits being 0.25 nmol L(-1) for 5-HT and 0.50 nmol L(-1) for 5-HIAA. The
      application of this method for the determination of 5-HT and 5-HIAA in urine
      samples from patients with acute appendicitis (AA) was satisfactory.

PMID- 16949891
TI  - Rapid GC-MS analysis of methamphetamine and its metabolites in urine--application
      of a short narrow-bore capillary column to GC-MS.
AB  - A rapid analysis of methamphetamine and its metabolites in urine was performed by
      gas chromatography-mass spectrometry (GC-MS) using a short narrow-bore capillary
      column (NBC) (5 m x 0.1 mm I.D.). For detection, selected ion monitoring (SIM)
      was performed for the characteristic ions of each of the compounds. The analytes
      were independently detected within 2 min. Linearity was demonstrated over a range
      from 25-2500 ng/ml. As an application of this study, a urine sample from a drug
      abuse suspect was analyzed. The analytes from the actual sample were detected
      with reasonable reproducibility. The results indicate the possibility of rapid
      analysis using a conventional GC-MS with a short NBC at a relatively low inlet
      pressure.

PMID- 16949890
TI  - Characterization of metabolites and cytochrome P450 isoforms involved in the
      microsomal metabolism of aconitine.
AB  - Aconitine, a major Aconitum alkaloid, is well known for its high toxicity that
      induces severe arrhythmias leading to death. The current study investigated the
      metabolism of aconitine and the effects of selective cytochrome P450 (CYP)
      inhibitors on the metabolism of aconitine in rat liver microsomes. The
      metabolites were separated and assayed by liquid chromatography-ion trap mass
      spectrometry (LC/MS(n)) and further identified by comparison of their mass
      spectra and chromatographic behaviors with reference substances. Various
      selective inhibitors of CYP were used to identify the isoforms of CYP, that
      involved in the metabolism of aconitine. A total of at least six metabolites were
      found and characterized in rat liver microsomal incubations. Result showed that
      the inhibitor of CYP 3A had an inhibitory effect on aconitine metabolism in a
      concentration-dependant manner, the inhibitor of CYP1A1/2 had a modest inhibitory
      effect, whereas inhibitors of CYP2B1/2, 2D and 2E1 had no obvious inhibitory
      effects on aconitine metabolism. Aconitine might be metabolized by CYP 3A and
      CYP1A1/2 isoforms in rat liver microsome.

PMID- 16949892
TI  - Thiophilic adsorption revisited.
AB  - Specific and efficient selection of serum immunoglobulins, but not other
      proteins, on T-gel remains difficult. T-gel capacity was determined for different
      activation conditions and serum loadings. Mass spectrometry analysis was used to
      identify the proteins found in the flow-through and in the eluted fractions.
      Alpha-2-macroglobulin and albumin were the major contaminants of the eluates. The
      influence of the competition between immunoglobulins and the other serum proteins
      on the adsorption was also studied. Using a serum depleted in immunoglobulins
      (flow-through of a first chromatography on T-gel), many serum proteins were
      retained on the T-gel, including albumin. We conclude that T-gel selectivity is
      less than absolute and may reflect for a large part the experimental conditions
      of the adsorption.

PMID- 16949893
TI  - Chromatographic-mass spectrometric methods for the quantification of L-arginine
      and its methylated metabolites in biological fluids.
AB  - L-Arginine (Arg) and its methylated metabolites play a major role in the
      synthesis of the cell signaling molecule nitric oxide (NO). Arg serves as a
      substrate for the enzyme NO synthase (NOS), which produces NO, whereas
      monomethylarginine (L-NMMA) and asymmetric dimethylarginine (ADMA) act as
      competitive inhibitors of NOS. Symmetric dimethylarginine (SDMA) has virtually no
      inhibitory effect on NOS activity, but shares the pathway for cell entry and
      transport with Arg and ADMA. Accurate and reliable quantification of these
      substances in various biological fluids is essential for scientific research in
      this field. In this review, chromatographic-mass spectrometric methods for Arg
      and its methylated metabolites ADMA and SDMA are discussed. Mass spectrometric
      detection provides an intrinsic higher selectivity than detection by means of UV
      absorbance or fluorescence. Taking advantage of the high selectivity, approaches
      involving mass spectrometric detection require less laborious sample preparation
      and produce reliable results. A consensus emerges that the concentration values
      in plasma of young healthy volunteers are about 65 microM for Arg, 0.4 microM for
      ADMA and 0.5 microM for SDMA.

PMID- 16949894
TI  - Sensitive quantification of atomoxetine in human plasma by HPLC with fluorescence
      detection using 4-(4,5-diphenyl-1H-imidazole-2-yl) benzoyl chloride
      derivatization.
AB  - The first HPLC-fluorescence method for the determination of atomoxetine in human
      plasma was developed and validated. Atomoxetine was derivatized with 4-(4,5
      diphenyl-1H-imidazol-2-yl) benzoyl chloride (DIB-Cl) under mild conditions, and
      separated isocratically on a C18 column using a HPLC system with fluorescence
      detection (lambdaex: 318 nm, lambdaem: 448 nm). A linear calibration curve was
      obtained over the concentration range 1-1000 ng/mL (r=0.999). The limit of
      detection (S/N=3) was 0.3 ng/mL. The relative standard deviations of intra-day
      and inter-day variations were < or =8.30% and 7.47%, respectively. This method is
      rapid, sensitive, and suitable for both basic and clinical studies of
      atomoxetine.

PMID- 16949895
TI  - LC/ESI-tandem mass spectrometric determination of bile acid 3-sulfates in human
      urine 3beta-Sulfooxy-12alpha-hydroxy-5beta-cholanoic acid is an abundant
      nonamidated sulfate.
AB  - We developed a highly sensitive and quantitative method to detect bile acid 3
      sulfates in human urine employing liquid chromatography/electrospray ionization
      tandem mass spectrometry. This method allows simultaneous analysis of bile acid 3
      sulfates, including nonamidated, glycine-, and taurine-conjugated bile acids,
      cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA),
      ursodeoxycholic acid (UDCA), and lithocholic acid (LCA), using selected reaction
      monitoring (SRM) analysis. The method was applied to analyze bile acid 3-sulfates
      in human urine from healthy volunteers. The results indicated an unknown compound
      with the nonamidated common bile acid 3-sulfates on the chromatogram obtained by
      the selected reaction monitoring analysis. By comparison of the retention
      behavior and MS/MS spectrum of the unknown peak with the authentic specimen, the
      unknown compound was identified as 3beta,12alpha-dihydroxy-5beta-cholanoic acid 3
      sulfate.

PMID- 16949896
TI  - A method for the estimation of femoral bone mineral density from variables of
      ultrasound transmission through the human femur.
AB  - Quantitative ultrasound (QUS) measurements at peripheral sites can be used to
      estimate osteoporotic fracture risk. However, measurements at these sites are
      less suitable to predict bone mineral density (BMD) or fracture risk at the
      central skeleton. We investigated whether direct QUS measurements at the femur
      would allow to estimate dual X-ray absorptiometry (DXA) BMD of the total proximal
      femur with errors comparable to established DXA accuracy errors. Two independent
      sets of femora were measured in Kiel (6 f, 4 m, age: 55-90) and Paris (19 f, 20 m
      age: 45-95) using different benchtop systems in the two laboratories. The femora
      were scanned in transverse transmission mode using focused US transducers of 500
      kHz center frequency. The QUS values were averaged over a region similar to the
      total hip region of dual X-ray absorptiometry (DXA) measurements. BMD was
      measured using DXA. SOS and BMD correlated significantly (p<0.0001) in both data
      sets (R2=0.81-0.93). Correlations between BUA and BMD were also significant at
      p<0.001, but correlation coefficients were lower (R2=0.61-0.75). Residual errors
      for the estimation of BMD were 8%-10% for SOS as predictor, and 14%-16% for BUA
      as predictor. The residual error of 8 to 10% for the estimation of BMD from SOS
      is comparable to variabilities among different DXA femur subregions and accuracy
      errors of femoral DXA measurements caused by the impact of soft tissue. It is
      substantially smaller than the errors of 13% for the estimation of total femur
      BMD from spine BMD, 14% for the estimation of total femur BMD from calcaneus SOS
      or 16% for the estimation of ash weight from DXA. The results of the study show
      that SOS is able to predict total BMD with adequate accuracy. If femoral BMD
      could be obtained in vivo with comparable accuracy, femoral QUS would be suited
      for the assessment of bone status at one of the main osteoporotic fracture sites.

PMID- 16949898
TI  - Body weight, early growth and antler size influence antler bone mineral
      composition of Iberian red deer (Cervus elaphus hispanicus).
AB  - Researchers have devoted little attention to the possibility that the chemical
      composition of bone might be variable under normal nutrition conditions. This
      study assessed antler bone composition of 25 one-year old deer (spikes). Antler
      content of ash, Ca, P, K, Na, Mg, Fe and Zn was assessed in base and tine, and
      the mean composition or the difference in composition between tine and base was
      used to explain variability in antler length, weight and perimeter. In turn, mean
      composition and difference in concentration of each mineral were related to body
      measures at 1 year of age, weight at birth, weight at 1 year of age and weight
      gains during lactation, or between weaning and year of age. Chemical composition
      differed between base and tine in ash, Ca, P, K, Zn and Fe, but not in Na or Mg.
      Composition explained a mean variability of 77% in antler length and weight. Body
      weight and size, in turn, influenced mineral composition. The greatest body
      effect was that of gains during lactation on principal components analysis factor
      related to Ca, P and other major minerals such as Na, K or Mg. Antler bone
      composition is variable in normal conditions and such variability may play a role
      in biomechanical properties of the antler, but it is also likely to show the
      nutritional status or physiological effort to grow antlers. Assessing bone
      composition may emerge as a new useful tool to obtain information regarding bone
      biology and its bearer in other species including ours.

PMID- 16949899
TI  - Over-expression of TIMP-1 in osteoblasts increases the anabolic response to PTH.
AB  - Intermittent PTH treatment induces structural changes that affect cancellous bone
      mass and have led to its indication for the treatment of osteoporosis. PTH is
      also known to upregulate the expression of matrix metalloproteinases (MMP) in
      osteoblasts. We wanted to find out whether inhibiting osteoblastic MMPs can
      affect the anabolic action of PTH in vivo. We had shown previously that mice over
      expressing TIMP-1 (tissue inhibitor of MMPs) specifically in osteoblasts display
      an increase in bone mineral density and bone mass combined with an overall
      decrease in bone turnover. In the present study, 10-week-old wild-type (WT) and
      transgenic (TG) mice were treated with PTH at 40 microg/kg/day for 1.5 months.
      DEXA analysis was performed before and after treatment, and histomorphometric and
      molecular analysis were carried out at the end of the experiment. Our findings
      indicate that the transgene boosted the anabolic action of PTH. The femurs of PTH
      treated TG mice displayed a greater increase in bone mineral density and
      trabecular bone volume than treated WT mice. Interestingly, the positive effect
      of the transgene on the action of PTH resulted from both reduced bone resorption
      activity and an increase in the bone formation rate. Osteoclastic surfaces that
      were increased in PTH-treated WT mice remained unchanged in TG mice, suggesting a
      decrease in osteoclastic differentiation. Histomorphometric data also indicate
      that PTH administration increased osteoblast activity in TG mice and affected the
      number of osteoblasts in WT mice. In conclusion, we demonstrate that inhibiting
      osteoblastic MMPs can potentiate the anabolic effect of PTH by decreasing
      osteoclast activity and increasing osteoblast activity. Our data also suggest
      that osteoblastic MMPs have some role in mediating the anabolic effects of PTH in
      vivo and indicate that inhibitors of MMPs could constitute a new therapy for
      degenerative diseases.

PMID- 16949900
TI  - Ultrasonic bone assessment: "the time has come".

PMID- 16949901
TI  - No associations between OPG gene polymorphisms or serum levels and measures of
      osteoporosis in elderly Australian women.
AB  - Bone mass is the single most important risk factor for osteoporotic fractures in
      the elderly and is mainly influenced by genetic factors accounting for 40-75% of
      the inter-individual variation. Critical for the bone remodeling process is the
      balance between the newly discovered members of the tumor necrosis factor ligand
      and receptor superfamilies, osteoprotegerin (OPG) and receptor activator of
      nuclear factor-kappaB ligand, which mediate the effects of many upstream
      regulators of bone metabolism. In the present study, we evaluated the impact of
      sequence variations in the OPG gene on bone mass, bone-related biochemistry
      including serum OPG and fracture frequency in elderly Australian women. A total
      of 1101 women were genotyped for 3 different single nucleotide polymorphisms
      (SNP) within the OPG gene (G1181C, T950C and A163G). The effects of these SNPs
      and serum OPG on calcaneal quantitative ultrasound measurements,
      osteodensitometry of the hip and bone-related biochemistry were examined. We
      found no significant relationship between sequence variations in the OPG gene or
      serum OPG and bone mass, bone-related biochemistry or fracture frequency. Our
      findings confirm some recent publications investigating the same SNPs but diverge
      from others, indicating that generalization of the relationships found in this
      type of study must be done with caution and signify the importance of determining
      associations between polymorphisms and osteoporosis in different ethnic groups.

PMID- 16949902
TI  - Re: "Incidence and characteristics of falls leading to hip fracture in Iranian
      population" by Abolhassani et al. BONE 2006:39;408-13.

PMID- 16949904
TI  - ADAMTS1 is regulated by interleukin-1beta, not by hypoxia, in chondrosarcoma.
AB  - Angiogenesis is characteristic of cartilage tumors, not of normal cartilage
      tissue. In addition to our previous report on differential expression of
      proangiogenic vascular endothelial growth factor A (VEGF-A) in cartilage tumors,
      we analyzed the expression of a disintegrin and metalloproteinase with
      thrombospondin motifs 1 (ADAMTS1), which has been identified as a potent
      inhibitor of VEGF-A. We further used a chondrosarcoma cell line to study the
      effect of interleukin (IL)-1beta and hypoxia on the regulation of ADAMTS1 and
      VEGF-A expression. ADAMTS1 was detected by reverse transcriptase-polymerase chain
      reaction and immunohistochemistry in all analyzed samples from enchondromas,
      conventional chondrosacromas, and dedifferentiated chondrosarcomas without
      exception. In contrast to previous reports on other cancers, we did not detect a
      consistent decrease in ADAMTS1 expression in chondrosarcomas. Interleukin-1beta
      stimulation, not hypoxia, transcriptionally downregulated ADAMTS1 in
      chondrosarcoma cells, whereas VEGF-A expression was upregulated either by hypoxia
      or IL-1beta. We conclude that ADAMTS1 and VEGF-A in chondrosarcoma cells are
      regulated independently from each other. We believe that IL-1beta has a stronger
      impact on vascularization in chondrosarcomas than hypoxia, as both factors,
      ADAMTS1 and VEGF-A, are regulated in a way that favors angiogenesis.

PMID- 16949905
TI  - The thyroid: an extremely rare primary site of neuroblastoma.
AB  - Neuroblastoma (NB) is uncommon in the adolescent age group. It is located at any
      site containing sympathetic neural tissue, with retroperitoneal and adrenal
      lesions being the most common. Cutaneous and subcutaneous metastases of NB in
      children are infrequent. Primary thyroid NB with regional lymph node and distant
      multiple subcutaneous metastases was diagnosed in an 11-year-old boy. The
      differential diagnosis was primitive neuroectodermal tumor. Our case demonstrates
      the unique presentation of NB in an adolescent.

PMID- 16949906
TI  - Basic fibroblast growth factor and fibroblastic growth factor receptor-1 may
      contribute to head and neck paraganglioma development by an autocrine or
      paracrine mechanism.
AB  - Paragangliomas are hypervascular tumors arising from neural crest-derived
      paraganglia that are associated with the autonomic nerve system. Mutations in
      genes coding for subunits of mitochondrial complex II are associated with
      hereditary paragangliomas, and it has been suggested that these mutations result
      in a pseudohypoxic signal triggering tumorigenesis. Fibroblastic growth factors
      are hypoxia-inducible angiogenic stimuli that are involved in the angiogenesis
      and tumorigenesis of several neoplasms. It has been demonstrated that basic
      fibroblastic growth factor (bFGF) is a survival factor for cultured chief cells
      of the carotid body, capable of inducing proliferation. To examine the role of
      this growth factor in paragangliomas, we studied the immunohistochemical
      expression of bFGF and its high affinity receptor fibroblastic growth factor
      receptor 1 (FGFR1) in 7 normal carotid bodies and in 33 head and neck
      paragangliomas, including 2 malignant cases and their metastases.
      Immunohistochemical expression of bFGF and FGFR1 in tumors was confirmed by real
      time polymerase chain reaction. FGFR1 was moderately present in carotid bodies,
      and there was strong and significantly enhanced cytoplasmatic staining of FGFR1
      in all paragangliomas. Chief cells in carotid bodies and tumors showed strong
      cytoplasmatic staining for bFGF. The results indicate that FGFR1 and bFGF may
      contribute to the development of head and neck paragangliomas.

PMID- 16949907
TI  - Expression of CDX2 in benign tissue and adenocarcinoma of the prostate.
AB  - Numerous studies have claimed that CDX2 is relatively specific and sensitive in
      establishing a gastrointestinal origin in metastatic tumors of unknown origin. We
      have recently seen 2 cases of prostatic adenocarcinoma (PCa) on needle biopsies
      with diffuse strong nuclear staining for CDX2 sent for consultation. One case was
      a prostatic duct adenocarcinoma in a man with a prostate-specific antigen (PSA)
      value of 327 ng/mL, and the other was a PCa with a Gleason score (GS) of 4 + 4 =
      8 in a man with a PSA value of 15 ng/mL. An adenocarcinoma with GS 3 + 3 = 6 from
      the contralateral side did not express CDX2. Because documented examples of this
      phenomenon are rare, we investigated the immunoexpression of CDX2, using tissue
      microarrays (TMAs). Three slides of TMAs were used to stain 708 tissue samples
      (0.6 mm in diameter) containing either benign or malignant prostate tissue, as
      well as control tissues from various anatomical sites including colon. In total,
      195 samples of primary PCa with GS of 6 (n = 41), 7 (n = 21), and 8 (n = 8); 195
      samples of benign prostate tissue; and 185 samples of metastatic PCa were
      studied. Of 70 radical prostatectomy specimens examined for PCa in TMAs, 4 (5.7%)
      were positive for CDX2, showing Gleason score of 6 (n = 3) and Gleason score of 7
      (n = 1). Focal moderate positive staining was seen in benign prostate tissue in 7
      (11.7%) of 60 radical prostatectomy specimens. None of the metastatic PCa
      expressed CDX2. CDX2 may uncommonly be focally expressed in benign prostatic
      glands. Staining in PCa is less common and appears independent of GS and is
      usually patchy and focal and of lesser intensity than in colonic tissue. However,
      rarely strong and diffuse staining may be seen. Positive CDX2 staining in high
      grade prostate cancer (ductal, cribriform, and solid) may be confused with
      secondary carcinoma of colonic origin. Routine histopathology, positive PSA
      immunostaining, and clinical findings can help confirm the correct diagnosis.

PMID- 16949908
TI  - Pulmonary vascular lesions in end-stage idiopathic pulmonary fibrosis:
      Histopathologic study on lung explant specimens and correlations with pulmonary
      hemodynamics.
AB  - In patients presenting with idiopathic pulmonary fibrosis (IPF), modifications of
      pulmonary vessels are well defined in fibrotic areas but have not been accurately
      assessed in the intervening patches of preserved lung. Moreover, the relation
      between pulmonary vessel lesions and pulmonary hemodynamics is not well known. We
      therefore designed a retrospective study on lung explant specimens from 26
      patients with a firm diagnosis of IPF who had undergone lung transplantation. Our
      aim was to (1) describe the vascular lesions, especially in preserved lung areas,
      and (2) correlate them with pulmonary hemodynamics. In dense fibrotic zones,
      thickening of the arterial and venous wall with severe luminal narrowing was
      present in each patient. In architecturally preserved lung zones, occlusion of
      venules and small pulmonary veins was observed in 65% of the patients, although
      there were only mild changes of muscular pulmonary arteries. We found a
      significant positive correlation between the macroscopic extent of lung fibrosis
      and mean pulmonary artery pressure, but we failed to find a relation between mean
      pulmonary artery pressure and venous/venular lesions in nonfibrotic areas. Our
      study points out that in many patients with IPF, nonfibrotic lung areas
      demonstrate an occlusive venopathy, the signification of which remains
      undetermined.

PMID- 16949909
TI  - Role of aspartyl-(asparaginyl) beta-hydroxylase in placental implantation:
      Relevance to early pregnancy loss.
AB  - Aspartyl-(asparaginyl) beta-hydroxylase (AAH) is a type 2 transmembrane protein
      with catalytic activity that hydroxylates epidermal growth factor-like domains of
      proteins that have a functional role in cell motility and invasion. Extravillous
      cytotrophoblasts (CTB) are motile and invasive unpolarized epithelial cells that
      mediate early implantation through interaction with the endometrium. This study
      characterizes the potential role of AAH in CTB implantation using human placentas
      from (1) terminated pregnancies (n = 11), (2) normal term deliveries (n = 21),
      (3) spontaneous abortuses (n = 21), and (4) small-for-gestational-age (SGA) term
      deliveries (n = 21). The SGA cases all had established clinical histories of
      intrauterine growth restriction or preeclampsia. Formalin-fixed, paraffin
      embedded sections of placenta were immunostained using the 15C7 monoclonal
      antibody generated to recombinant AAH. In addition, snap-frozen or RNAlater
      preserved specimens (Ambion, Austin, TX) were used for RNA analysis of AAH
      expression by real-time quantitative reverse transcriptase-polymerase chain
      reaction and protein analysis by Western blotting. The immunohistochemical
      staining studies demonstrated AAH expression in amniocytes, villous CTB,
      syncytiotrophoblast, extravillous CTB, decidua, and endometrial glands at all
      gestational ages and in all 4 groups. Higher levels of AAH immunoreactivity were
      observed in extravillous CTB compared with villous CTB. Immunohistochemical
      staining and RNA analysis demonstrated abundant AAH expression in placental
      trophoblastic cells as well as in decidua and endometrial glands, with reduced
      expression in spontaneous abortion and SGA, suggesting that AAH may serve as a
      biomarker of impaired implantation. The high levels of AAH in decidua and
      endometrial glands suggest a role for this molecule in "receptivity" of
      endometrium.

PMID- 16949910
TI  - Decreased expression of annexin A1 is correlated with breast cancer development
      and progression as determined by a tissue microarray analysis.
AB  - Annexin A1 (ANXA1) is a calcium- and phospholipid-binding protein and a known
      mediator of glucocorticoid-regulated inflammatory responses. Using a combined
      multiple high-throughput approach, we recently identified a reduced expression of
      ANXA1 in human breast cancer. The finding was confirmed at the gene level by
      quantitative reverse transcription-polymerase chain reaction and at the protein
      level by immunohistochemical staining of normal, benign, and malignant breast
      tissues. In this study, we constructed and used a high-density human breast
      cancer tissue microarray to characterize the expressional pattern of ANXA1
      according to histopathologies. The tissue microarray contains 1,158 informative
      breast tissue cores of different histologies including normal tissues,
      hyperplasia, in situ and invasive tumors, and lymph node metastases. Our results
      showed that there was a significant decrease in glandular expression of ANXA1 in
      ductal carcinoma in situ and invasive ductal carcinoma compared with either
      normal breast tissue or hyperplasia (P < .0001). Moreover, in benign breast
      tissue, myoepithelial cells showed strong expression of ANXA1. There was a
      decrease of ANXA1 expression in myoepithelial cells in ductal carcinoma in situ
      lesions compared with the same cell population in either normal or hyperplastic
      lesions. These results suggest that suppressed ANXA1 expression in breast tissue
      is correlated with breast cancer development and progression.

PMID- 16949911
TI  - Correlation of cyclin D1 and E1 expression with bladder cancer presence,
      invasion, progression, and metastasis.
AB  - The objective of this study was to determine the correlation of the expression of
      cyclin D1 and E1 with the expression of commonly altered cell cycle regulators
      and bladder cancer presence, staging, and clinical outcomes. We performed
      immunohistochemical staining for cyclin D1, cyclin E1, p53, p21, p27, and
      retinoblastoma protein (pRB) on serial cuts from normal urothelium from 9
      controls, radical cystectomy specimens from 226 consecutive patients with
      advanced transitional cell carcinoma, and lymph nodes with metastasis from 50 of
      the 226 cystectomy patients. Cyclin D1 and E1 immunoreactivity were considered
      low when samples demonstrated less than 10% and 30% nuclear reactivity,
      respectively. Normal bladder urothelium from all 9 control patients showed
      uniformly intense expression of cyclin D1 and E1. Cyclin D1 expression was low in
      99 (43.8%) of 226 cystectomy specimens and 25 (50.0%) of 50 metastatic lymph node
      specimens. Cyclin D1 immunoreactivity was not associated with any pathologic
      characteristics or clinical outcomes. Cyclin E1 expression was low in 125 (55.3%)
      of 226 cystectomy specimens and 22 (44.0%) of 50 metastatic lymph node specimens.
      Low cyclin E1 expression was significantly associated with advanced pathologic
      stage, lymphovascular invasion, and lymph node metastases. In multivariate
      analyses, low cyclin E1 expression was significantly associated with bladder
      cancer-specific mortality (P = .048), but not disease recurrence (P = .056). Low
      cyclin E1 expression was significantly associated with altered expression of pRB,
      p27, and cyclin D1. Low cyclin D1 expression was significantly associated with
      altered expression of pRB, p21, and cyclin E1. Cyclin E1 expression stratifies
      patients with bladder transitional cell carcinoma into those with more "indolent"
      behavior and those with features of biologically and clinically aggressive
      disease.

PMID- 16949912
TI  - Infrequent COX-2 expression due to promoter hypermethylation in gastric cancers
      in Dalian, China.
AB  - Cyclooxygenase-2 (COX-2) has been shown to play oncogenic roles during stepwise
      gastrocarcinogenesis, and its expression is correlated with Helicobacter pylori
      infection, tumor necrosis factor alpha-mediated nuclear factor (NF)-kappaB
      activation, and Wnt signaling. To examine COX-2 expression and the status of its
      regulatory factors, we examined 49 gastric cancers (GCs), 21 premalignant
      tissues, and 10 noncancerous gastric mucosa from residents of Dalian, China.
      Unexpectedly, it was found that COX-2 expression was infrequent in the gastric
      samples (18.8%, 15/80) regardless of the type of lesion or morphological
      phenotype. H pylori infection was detected in 19 of 35 tested GC cases. Tumor
      necrosis factor alpha expression, NF-kappaB nuclear translocation, or Wnt2
      overexpression was observed in 56 (82.3%) of 68, 40 (50.0%) of 80, and 62 (77.5%)
      of 80 of the gastric tissue samples, respectively. Methylation-sensitive
      restriction enzyme digestion followed by polymerase chain reaction of COX-2
      promoter regions revealed a remarkably high hypermethylation rate (100%, 20/20)
      among the COX-2-negative GCs, which was associated with the overexpression of DNA
      methyltransferase (DNMT) 1 (r = 0.587, P < .01). These results indicate that (1)
      in contrast to previous findings using other GC sources, our results show that
      COX-2 activity may not be a critical molecular event during GC formation, (2) the
      tumor-promoting effects of H pylori infection and Wnt and NF-kappaB activities
      may be mediated by COX-2-independent pathways, and (3) promoter hypermethylation
      is the major cause of COX-2 silencing in Dalian GCs, apparently because of
      increased expression of DNMTs (especially DNMT1). Consequently, a COX-2-oriented
      preventive or therapeutic strategy is not practical for Dalian GCs. The frequent
      COX-2 hypermethylation observed in Dalian GCs could have insightful epigenetic
      and epidemiologic implications.

PMID- 16949913
TI  - Multiplex short tandem repeat DNA analysis confirms the accuracy of p57(KIP2)
      immunostaining in the diagnosis of complete hydatidiform mole.
AB  - Detailed histopathologic examination remains to be the basis for the diagnosis of
      hydatidiform mole (HM). However, poor sampling, necrosis, and earlier uterine
      evacuation can lead to uncertainty in the diagnosis. Also, the criteria are
      subjective, resulting in considerable interobserver variability. The p57(KIP2)
      gene is paternally imprinted and maternally expressed, and the presence of its
      protein product serves as a surrogate marker for the nuclear maternal genome.
      Because a complete HM (CHM) is the only type of conceptus lacking a maternal
      contribution, p57(KIP2) immunostaining is correspondingly absent, whereas it is
      present in CHM mimics. Although analysis of DNA microsatellite polymorphisms is a
      reliable method for the diagnosis and classification of HM, it is not universally
      available. To assess the relative accuracy of p57(KIP2) immunostaining and
      molecular diagnosis by nuclear DNA microsatellite polymorphisms in discriminating
      CHM from its mimics, we analyzed archival tissue from 33 case patients (7 with a
      definitive diagnosis of CHM, 16 with a possible diagnosis of HM, and 10 with
      normal placentas) by both methods. Concordant results were obtained in all cases,
      and p57(KIP2) immunostaining accurately identified all cases of CHM from the
      groups with a definitive or possible diagnosis of HM. p57(KIP2)
      immunohistochemistry is a time- and cost-effective means of distinguishing CHM
      from its mimics in challenging cases.

PMID- 16949914
TI  - Glypican-3 expression in hepatocellular tumors: diagnostic value for
      preneoplastic lesions and hepatocellular carcinomas.
AB  - Glypican-3 (GPC3), a member of heparan sulfate proteoglycans, plays a role in
      cell growth, differentiation, and migration. The objectives of this study were to
      assess the diagnostic value of GPC3 immunostaining in hepatocellular carcinomas
      (HCCs) and to analyze its expression profile in preneoplastic lesions. Tissue
      microarrays were built by sampling 54 HCCs and adjacent liver tissues (21
      developing from cirrhosis and 33 from normal liver) and 94 cirrhotic
      macronodules. Fourteen typical liver cell adenomas and 5 with malignant foci were
      also included. Sections were assessed for GPC3 expression by
      immunohistochemistry. GPC3 staining was observed in 19 (90%) of 21 HCC cases with
      cirrhosis and in 18 (64%) of 28 HCC cases with normal liver (P < .01). When
      staining was positive, it was both membranous and cytoplasmic. Positive staining
      was observed in 1 case of nonneoplastic adjacent liver. In cases of adenomas,
      only malignant foci were positive. Among the 94 macronodules, GPC3 immunostaining
      was noted in 48% (14/29) of high-grade dysplastic or early HCC and in 3% (2/65, P
      < .001) of benign or low-grade dysplastic macronodules. This study shows that
      GPC3 is an efficient diagnostic marker of HCC, potentially useful in the
      differential diagnosis of liver cell adenomas and well-differentiated HCC. Our
      results also suggest that GPC3 may be considered as an early marker of liver
      carcinogenesis because it is able to identify some cirrhotic macronodules with
      malignant potential.

PMID- 16949915
TI  - Loss of extracellular E-cadherin in the normal mucosa of duodenum and colon of
      patients with familial adenomatous polyposis.
AB  - The duodenum is the main site for (pre-) malignant extracolonic manifestations in
      patients with familial adenomatous polyposis (FAP). Changes in the E
      cadherin/beta-catenin complex play a pivotal role in the development of
      malignancies. Loss of E-cadherin has been described in association with loss of
      SMAD4. To elucidate the pathways leading to the development of duodenal adenomas
      in patients with FAP, the distributions of E-cadherin, SMAD4, and beta-catenin
      were analyzed. Furthermore, differences between the duodenum and colon were
      evaluated. Normal FAP duodenum (n = 13) and FAP duodenal adenomas (n = 50; total,
      21 patients) were compared with non-FAP duodenal adenomas (n = 7) and normal non
      FAP duodenum (n = 15) by immunohistochemical staining for extracellular and
      intracellular E-cadherin, beta-catenin, and SMAD4. Colonic biopsies of 10
      patients with FAP were also studied, as well as non-FAP colonic adenomas (n = 26)
      and non-FAP normal colon (n = 12). Compared with the intracellular component of E
      cadherin that was present in all cases, a significant loss of extracellular E
      cadherin was observed in both duodenal and colonic adenomas and normal tissue of
      patients with FAP. Nuclear localization of beta-catenin was more often observed
      in duodenal FAP adenomas compared with non-FAP adenomas. Loss of nuclear SMAD4
      was seen in the duodenum and, to a higher degree, in the colon of patients with
      FAP, as well as non-FAP patients. The loss of extracellular E-cadherin in the
      normal duodenal and colonic mucosa of patients with FAP might play a role in the
      high susceptibility of these tissues for (pre-) malignant transformation.

PMID- 16949916
TI  - Inverted urothelial papillomas with foamy or vacuolated cytoplasm.
AB  - Inverted papillomas of the bladder are uncommon benign neoplasms characterized by
      endophytic growth of urothelial cells as anastomosing cords, displaying minimal
      cytologic atypia. Reports of inverted papilloma associated with urothelial
      carcinoma or urothelial carcinoma arising within inverted papilloma highlight the
      difficulties in evaluating urothelial lesions with inverted growth patterns.
      Within the spectrum of findings in inverted papilloma, vacuolization and foamy
      (xanthomatous-appearing) cytoplasmic changes have not been previously reported.
      In the current study, we present 5 novel cases of inverted papilloma involving 2
      men and 3 women ranging in age from 48 to 88 years, who presented with
      microhematuria (n = 3) or irritative symptoms (n = 2). Cystoscopically, the
      lesions were polypoid (n = 3), pedunculated (n = 1), or solid (n = 1), measured
      between 0.7 and 2.5 cm, and were all located at the trigone or bladder neck.
      Morphologically, all cases had some component of usual inverted papilloma along
      with areas displaying foamy or vacuolated cytoplasm encompassing 30% to 90% of
      the lesion. These "clear cells" were seen both in distinct regions within the
      biopsy and, more frequently, intermingled with usual inverted papilloma cells. In
      3 of 5 cases, these findings were sufficiently unusual to cause confusion with
      urothelial carcinoma. The diagnostic dilemma encountered in these cases of
      inverted papilloma with foamy or vacuolated cytoplasm warrants their distinction
      from other benign and malignant urothelial lesions with inverted growth and/or
      clear cell features.

PMID- 16949917
TI  - Atypical immature cervical metaplasia: immunoprofiling and longitudinal outcome.
AB  - Atypical proliferations of immature cervical squamous metaplasia were reviewed
      and correlated with p16 and Ki-67 expression to determine whether immunoprofiling
      could enable more conventional classification. The longitudinal outcome of
      atypical immature metaplasia (AIM) and predictive role of biomarker expression
      were also investigated. All atypias of immature squamous metaplasia in the year
      2000 were reviewed and stained with p16 and Ki-67. Biomarker features were
      evaluated and the Ki-67 index calculated. Diagnoses were correlated with the
      immunoprofile of each antibody, both separately and combined. The progression to
      squamous intraepithelial lesion (SIL) of lesions reclassified as AIM was
      determined, and biomarker immunoprofiles were correlated with outcome. The 172
      atypias were reviewed as 3 (1.7%) negative, 54 (31.4%) benign, 60 (34.9%) AIM, 43
      (25%) low-grade SIL (LSIL), and 12 (6.9%) high-grade SIL (HSIL). HSIL correlated
      significantly with a combined high index (>15%) and p16 diffusely positive
      profile (P = .01). Benign diagnoses correlated significantly with a low index (1%
      15%) and p16 negative or focal profile (P = .01). AIM and LSIL correlations were
      not significant, but their profiles were very variable and nearly identical. AIM
      was the only pathology in 43 cases, and follow-up was available for 32 (74.4%).
      SIL developed in 66% (50% LSIL and 16% HSIL) and p16 positivity correlated (P =
      .02). p16 and Ki-67 immunoprofiling are reliable in reclassifying some atypical
      proliferations of immature squamous metaplasia as HSIL and some as benign. The
      similarity between AIM and LSIL in regard to their immunoprofile as well as
      outcome suggests AIM is a morphological type of LSIL.

PMID- 16949918
TI  - Immunohistochemical evidence of Clostridium sp, Staphylococcus aureus, and group
      A Streptococcus in severe soft tissue infections related to injection drug use.
AB  - Severe soft tissue infections are caused by either single or multiple
      microorganisms. We performed a retrospective immunohistochemical (IHC) study on
      formalin-fixed, paraffin-embedded soft tissue samples from 20 injection drug
      users who were part of a cluster of severe illness and death after skin and soft
      tissue infections in Scotland and Ireland in 2000. The IHC assays used antibodies
      against Clostridium sp, Staphylococcus aureus, group A streptococci, and Bacillus
      anthracis. Intact bacilli and granular Clostridium antigen staining in areas with
      necrosis, edema, and inflammation were observed in skin, fascia, or muscle
      samples of 12 (60%) patients. A variety of clostridia were isolated from affected
      soft tissues in 10 IHC-positive cases. Staphylococcus aureus antigens were
      observed in 3 cases including 1 where S aureus was isolated, 1 with negative
      cultures, and 1 where mixed cultures were obtained. Group A streptococcal
      antigens were observed in 1 case in which Streptococcus pyogenes and S aureus
      were isolated. By using IHC, we detected different bacteria in archival soft
      tissue samples from patients with severe skin and soft tissue infections.
      Immunohistochemical assays can be of great diagnostic value, particularly for
      bacteria such as Clostridium sp, which are difficult to isolate because of their
      anaerobic fastidious growth requirements.

PMID- 16949919
TI  - Histologic variants of urothelial carcinoma: differential diagnosis and clinical
      implications.
AB  - An increasing number of histologic variants of urothelial carcinoma have been
      recognized in recent years. It is important for surgical pathologists to be aware
      of these morphological variants that, on occasion, may lead to misinterpretation
      as benign. Some also require a specific therapeutic approach. In this article, we
      review the most common histologic variants of urothelial carcinoma of the
      bladder. Emphasis is placed on clinical significance and differential diagnosis.

PMID- 16949920
TI  - Topoisomerase IIalpha gene amplification in gastric carcinomas: correlation with
      the HER2 gene. An immunohistochemical, immunoblotting, and multicolor
      fluorescence in situ hybridization study.
AB  - Topoisomerase IIalpha (topoIIalpha) is an enzyme required for DNA replication and
      a molecular target for drugs called anthracyclines. The topoIIalpha gene (TOP2A)
      is located close to the HER-2/neu oncogene (HER2). We assessed gastric cancers to
      (1) clarify the relationship between gene amplification and protein
      overexpression of topoIIalpha and HER2; (2) evaluate the correlation between gene
      amplification and protein overexpression of topoIIalpha; and (3) examine the
      relationship between the results of immunohistochemistry and Western blot
      analysis for topoIIalpha. In a combined analysis of immunohistochemistry and
      fluorescence in situ hybridization on 552 formalin-fixed and paraffin-embedded
      gastric cancer tissues, 38 cases were found to have HER2 amplification. Further
      examination by fluorescence in situ hybridization revealed amplification of TOP2A
      in 13 of the 38 cases. No aberrations in the TOP2A gene were observed in cases
      without HER2 overexpression, except for one containing a gene deletion. The
      TopoIIalpha protein-labeling index was not correlated with TOP2A amplification.
      Fluorescence in situ hybridization was performed on nuclear imprint specimens
      obtained from 9 cases using simultaneous probes for TOP2A, HER2, and centromere
      17. Of these 9 cases, 3 displayed coamplification of TOP2A and HER2, and only 1
      of the 3 cases revealed a high expression of topoIIalpha in Western blot.
      Although patients having gastric adenocarcinoma with TOP2A amplification could be
      considered suitable for clinical trials, information involving anthracycline
      therapy is not firmly understood in regards to the status of TOP2A amplification
      or protein overexpression. Therefore, results of the current study will provide
      further insight for the clinical application of anthracycline in gastric cancers.

PMID- 16949921
TI  - PIK3CA gene mutations in endometrial carcinoma: correlation with PTEN and K-RAS
      alterations.
AB  - Alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway are
      common in endometrial carcinoma. Inactivation of the tumor suppressor gene PTEN
      leads to a constitutively active PI3K pathway, which plays a role in the early
      steps of endometrial tumorigenesis. Other alterations in the PI3K/AKT pathway are
      mutations in the PIK3CA gene, which encode the p110alpha catalytic subunit of
      PI3K. PIK3CA mutations cluster to the helical (exon 9) and the kinase (exon 20)
      domains of the gene. In endometrial carcinomas, PIK3CA mutations have been found
      to coexist frequently with PTEN mutations, but it is not clear whether they occur
      in cells with monoallelic or biallelic inactivation of PTEN. In the present study
      we have evaluated PIK3CA mutational status in a series of 33 endometrial
      carcinomas, previously screened for microsatellite instability and mutations in
      PTEN, K-RAS, and CTNNB-1. The tumors were also evaluated for loss of
      heterozygosity on 10q23 and hypermethylation of the promoter region of
      PTEN/psiPTEN to assess the monoallelic or biallelic inactivation status of PTEN.
      PIK3CA mutations were detected in 8 (24%) of the 33 cases. Seven mutations were
      located in exon 20 and 1 in exon 9. PTEN alterations were found in 19 cases
      (57%). Biallelic inactivation of PTEN was demonstrated in 11 tumors, whereas 8
      tumors exhibited alteration in only 1 of the 2 alleles. PIK3CA mutations
      coexisted with monoallelic alterations of PTEN in 4 cases (2 mutations and 2
      allelic imbalances), with biallelic PTEN inactivation in 1 case (mutation and
      promoter methylation), and 3 tumors showed PIK3CA mutations in association with
      wild-type PTEN. PIK3CA mutations did not correlate with microsatellite
      instability or mutations in CTNNB-1. However, PIK3CA and K-RAS mutations (8
      cases) were mutually exclusive alterations. In summary, the results confirm that
      PIK3CA mutations are frequent in endometrial carcinoma and support the hypothesis
      that PIK3CA mutations may have an additive effect to PTEN monoallelic
      inactivation in endometrial carcinoma.

PMID- 16949922
TI  - Frequent detection of the JAK2 V617F mutation in bone marrow core biopsy
      specimens from chronic myeloproliferative disorders using the TaqMan polymerase
      chain reaction single nucleotide polymorphism genotyping assay: a retrospective
      study with pathologic correlations.
AB  - A retrospective investigation of the JAK2 V617F mutation was carried out in DNA
      samples from 131 bone marrow (BM) core biopsy specimens corresponding to patients
      with polycythemia vera (PV) (n = 31), essential thrombocythemia (ET) (n = 31),
      chronic idiopathic myelofibrosis (CIM) (n = 18), as well as patients with normal
      BM and secondary reactive hyperplasia. We used the TaqMan polymerase chain
      reaction single nucleotide polymorphism genotyping assay to detect the specific
      JAK2 mutation. This technique allowed us to detect the JAK2 V617F mutation in a
      population containing at least 5% of homozygous mutants. Overall, the incidence
      of the JAK2 V617F mutation was 87% in PV, 67% in ET, and 66% in CIM. This
      approach proved to be reliable and more sensitive in detecting the mutation
      compared with that of initial studies on different materials but similar to that
      of recent work with various polymerase chain reaction-based techniques. Two
      essential findings arose from our study. First, this technique could be carried
      out with DNA samples, even partially degraded, from routinely processed BM core
      biopsy specimens. Second, after correlation with morphological features, it
      turned out that the characteristics of the megakaryocytes were more specific than
      the mutational status of JAK2 in characterizing ET and CIM. Concerning PV, as
      expected, the incidence of the JAK2 mutation was higher, but the morphological
      criteria were misleading in some cases, strongly suggesting that the combination
      of both histologic and molecular data would enable the characterization of
      virtually all cases.

PMID- 16949923
TI  - Cellular and reticular variants of hemangioblastoma differ in their cytogenetic
      profiles.
AB  - Capillary hemangioblastomas of the central nervous system are benign tumors and
      occur either sporadically or as a manifestation of von Hippel-Lindau disease. A
      rarer cellular and a more common reticular variant can be distinguished on the
      basis of the abundance of the stromal cell component, with the cellular variant
      being significantly associated with a greater probability of recurrence. To
      investigate whether these subtypes differ in their cytogenetic profile, a
      comparative genomic hybridization analysis of 10 cellular and 10 reticular
      hemangioblastomas was undertaken. Comparative genomic hybridization revealed DNA
      copy number changes in 14 of 20 cases (8 of 10 cellular and 6 of 10 reticular
      hemangioblastomas). The most common changes overall were losses of chromosomes 19
      (35%), 6 (30%), and 22q (15%), whereas loss of 3 and gain of 4 were encountered
      in one case each (5%). The cellular variant showed losses of chromosomes 6 (60%),
      22q and 19 (20% each), as well as gain of 4 (10%), whereas the reticular variant
      presented with losses of chromosomes 19 (50%), 22q and 3 (10% each). Loss of
      chromosome 6 was significantly associated with the cellular subtype (P < .005),
      whereas loss of 19/19p was found more frequently in the reticular variant, albeit
      not significantly (P = .16). In conclusion, our data may point toward different
      genetic pathways in the pathogenesis of the 2 histologic subtypes of capillary
      hemangioblastoma.

PMID- 16949924
TI  - Use of X-chromosome inactivation pattern to determine the clonal origins of
      uterine leiomyoma and leiomyosarcoma.
AB  - Uterine leiomyomas (LMs) and leiomyosarcomas (LMSs), both of smooth muscle
      origin, sometimes coexist in the same uterus. Little genetic evidence exists
      concerning the developmental relationship between LM and LMS. Using the X
      chromosome inactivation pattern of the human androgen receptor gene, we examined
      the clonality of LM and LMS. Of the 24 patients with LM, 21 had multiple
      neoplasms; all were clonal and individual LMs derived from separate clones. Of
      the 20 patients with LMS, 6 exhibited multiple tumors in the uterus, and 4 of
      these individuals also harbored coexisting uterine LMs. We found all LMSs to be
      clonal. Separate tumors showed identical pattern of X inactivation in 4 patients,
      and in 2 other individuals, multiple LMSs developed from independent clones.
      Among the 4 patients with LMS and coexisting LM, 3 showed the same pattern of X
      inactivation in LMS and the adjacent LM. In 2 of the 3 patients, the tumor also
      exhibited a morphological transition between benign cells in LM and malignant
      cells in LMS, supporting the possibility of transformation from LM to LMS. One
      patient displayed different clones in LMS and the coexisting LM, indicating their
      independent origins. We conclude that (i) both LM and LMS are clonal; (ii)
      different nodules in multiple LM are of independent origins; (iii) multiple
      lesions of LMS may be either monoclonal or multiclonal; (iv) most LMSs are
      solitary lesions and are most likely de novo, but an individual LM may undergo
      "malignant transformation" to a LMS; and (v) some LMSs and coexisting LMs are of
      independent origins.

PMID- 16949925
TI  - Evaluation of urokinase plasminogen activator and its receptor in different
      grades of human prostate cancer.
AB  - Increased expression of urokinase plasminogen activator (uPA) and its receptor
      (uPAR) has been reported in various malignancies including prostate cancer (CaP).
      However, their expression in the different grades of CaP remains poorly
      understood. Here, we use tissue microarrays to examine the expression of uPA and
      uPAR in different grades of human CaP and to establish the potential of these
      tumor-associated antigens as candidates for targeted therapy. One hundred twenty
      paraffin-embedded specimens were selected from patients who underwent radical
      retropubic prostatectomy or transurethral resection of the prostate for primary
      untreated CaP and 10 matched lymph node metastases. Monoclonal antibodies #394
      and #3936 were used on tissue microarrays with standard immunohistochemistry to
      examine uPA and uPAR expression, respectively. Overexpression of uPA and uPAR was
      detected in 53% and 64% of primary CaP tissues, respectively, and in more than
      90% of lymph node metastases, but not in normal prostates or benign tissues. Of
      the uPA and uPAR positive tumors, 76% and 68% were Gleason score 7 or higher,
      respectively, and most of these tumors also showed stromal staining. The
      overexpression of uPA and uPAR was highly related to tumor differentiation in
      patients with CaP. Both uPA and uPAR proteins are candidate therapeutic targets
      for cancer therapy to control micrometastases and hormone refractory disease in
      CaP.

PMID- 16949926
TI  - Syncytial giant cell hepatitis in human immunodeficiency virus-infected patients
      with chronic hepatitis C: 2 cases and review of the literature.
AB  - Syncytial giant cell hepatitis (SGCH) among adult human immunodeficiency virus
      (HIV)-infected patients has been rarely described. Most cases have been reported
      in subjects coinfected with the hepatitis C virus (HCV), but its prevalence and
      outcome remain unknown. We performed a retrospective analysis of all cases of
      SGCH among 332 liver biopsies from HIV-infected patients seen at a tertiary
      center in Madrid, Spain, between 1984 and March 2004. Two hundred fifty specimens
      were obtained from HCV-coinfected patients. There were 2 cases of SGCH, leading
      to an observed overall prevalence of 0.6% (0.8% when considering only HCV
      coinfected patients). In addition to histological changes secondary to chronic
      hepatitis C, the liver cords were replaced by syncytial giant cells with up to 30
      nuclei. There was no histological evidence of measles (among paramyxoviruses) or
      herpes viruses group infections. In patient 1, there was a progressive clinical
      worsening after a 3-month course of prednisone, leading to liver failure and
      death. His postmortem liver biopsy showed more abundant giant hepatocytes
      accompanied with the development of a histologic pattern of severe fibrosing
      cholestatic hepatitis. The second patient received a prolonged course of
      pegylated interferon-alpha-2b and ribavirin with clearance of syncytial giant
      hepatocytes despite HCV-RNA persistence. SGCH is a rare histological finding
      among HIV-infected patients with chronic hepatitis C. Specific treatment with
      pegylated interferon and ribavirin can lead to histological resolution and
      biochemical improvement, even in the absence of HCV-RNA clearance.

PMID- 16949927
TI  - Expression of vitamin D3 receptor in kidney tumors.
AB  - The kidney is not only a primary vitamin D target organ but also is a key site of
      vitamin D metabolism. Recent studies have shown that vitamin D has important
      physiologic effects on proliferation and differentiation in a variety of benign
      and malignant cells. Our preliminary immunohistochemical study showed that
      vitamin D receptor (VDR) was highly expressed in renal distal tubules and
      collecting ducts, whereas the renal proximal tubules and glomeruli did not
      express VDR. These observations led us to study the expression of VDR in various
      kidney tumors to determine the possible diagnostic utility of VDR. Paraffin
      tissue microarray (TMA) blocks were constructed containing core cylinders from
      clear cell (52), papillary (35), chromophobe (20), sarcomatoid (20), and
      metastatic (59) renal cell carcinomas (RCCs). Oncocytomas (20), normal adult
      kidneys (12), and normal adult adrenals (6) were also included. In addition, 30
      clear cell RCCs and 3 collecting duct carcinomas were also studied using
      conventional sections. Furthermore, VDR messenger RNA and protein expression was
      also quantified using real-time reverse transcriptase-polymerase chain reaction
      and Western blot analysis. Vitamin D receptor was strongly positive in collecting
      duct carcinomas (100% [3/3], cytoplasmic), papillary RCCs (94% [33/35],
      cytoplasmic), chromophobe RCCs (85% [17/20], membranous), and oncocytomas (90%
      [18/20], cytoplasmic with perinuclear accentuation). In contrast, VDR expression
      was focal/weak and present only in the peripheral regions of clear cell RCCs.
      Vitamin D receptor was weakly positive in sarcomatoid variant RCCs (88% [14/16])
      regardless of the type of associated original RCC. Overall, VDR is a
      discriminative marker for renal cell tumors. The preferential expression of VDR
      in chromophobe RCCs, oncocytomas, and collecting duct carcinomas is in agreement
      with the concept that these tumors differentiate toward epithelium lining the
      distal convoluted tubules and collecting ducts. Considering the different VDR
      expression patterns, VDR is a useful ancillary tool in distinguishing chromophobe
      RCCs from oncocytomas. In addition, the focal and much weaker VDR expression in
      clear cell RCCs makes VDR valuable in distinguishing clear cell RCC from other
      types of RCCs.

PMID- 16949928
TI  - Incidence and prognostic significance of occult tumor cells in lymph nodes from
      patients with stage IIA colorectal carcinoma.
AB  - Approximately 30% of patients with lymph node (LN)-negative colorectal carcinoma
      (CRC) die of tumor recurrence, which can be related to the presence of tumor
      cells in LNs not detected by conventional histopathologic analysis. However, the
      prognostic significance of occult cancer cells still remains uncertain. We
      evaluated the incidence and the prognostic significance of occult cancer cells in
      LNs from 395 consecutive patients with curatively resected stage IIA CRC using
      immunohistochemistry for cytokeratin 20. Immunostained tumor cells were
      categorized as micrometastases (MCMs) or isolated tumor cells (ITCs) according to
      the American Joint Committee on Cancer criteria. The detection rates were
      compared with the clinicopathologic characteristics of the patients and with
      cancer-specific survival. The median follow-up time was 128 months.
      Micrometastases were detected in 39 patients (9.9%), whereas ITCs were found in
      112 (28.4%), for an overall frequency of 38.2%. None of the clinicopathologic
      parameters examined was correlated with the presence of occult cancer cells.
      Patients with ITCs and those with negative LNs showed a similar survival rate
      (77.7% and 78.3%, respectively), whereas patients with MCMs had a lower survival
      rate (64.1%). At the univariate analysis, MCMs, tumor growth pattern, extent of
      tumor spread, and Crohn's-like lymphoid reaction influenced the survival rate
      significantly. Nevertheless, at the multivariate analysis, only the pattern of
      tumor growth and the extent of tumor spread were independent prognostic factors.
      The detection of immunostained tumor cells in the LNs of patients with stage IIA
      CRC occurs relatively frequently but has no significant effect on prognosis.

PMID- 16949929
TI  - Expression of betacellulin and epidermal growth factor receptor in hepatocellular
      carcinoma: implications for angiogenesis.
AB  - Hepatocellular carcinoma (HCC) is becoming one of the common malignant tumors
      worldwide and is characterized by high vascularity. Angiogenesis (formation of
      new microvessels) is critical for growth and progression of various human solid
      tumors. Betacellulin (BTC) is a member of the epidermal growth factor (EGF)
      family, and its signal action is mediated through EGF receptors (EGFR). In this
      study, to understand the role of BTC in relation to EGFR in HCC, we examined
      localization, expression, and involvement in angiogenesis of BTC and EGFR. The
      results revealed that expression of BTC, EGFR, and tumor growth factor-alpha
      messenger RNA in HCC was increased by 80%, 60%, and 40%, respectively, as
      compared with those in the nontumorous tissues. Increased expression of BTC
      protein was observed in 31 (61%) of 51 HCC specimens, and the level of tumor
      growth factor-alpha protein was higher in 17 (33%) of 51 HCC specimens than in
      nonmalignant hepatocytes. Betacellulin was predominantly expressed in HCC cells,
      whereas EGFR was observed in sinusoidal endothelial cells of HCC in 25 tumors
      (49%). Betacellulin was secreted in all 4 examined HCC cell lines. The HCC
      specimens showing positive EGFR expression in tumor endothelial cells had a
      significantly higher microvessel density than those without EGFR expression (P <
      .005). A strong correlation was found between BTC expression in cancer cells and
      EGFR expression in tumor endothelial cells (P < .001). These findings suggest
      that overexpression of BTC by HCC cells and EGFR by tumor endothelial cells
      enhance vascularity in a paracrine manner.

PMID- 16949930
TI  - Fatty lesions of the atria and interatrial septum.
AB  - Lipomatous lesions of the heart involving the atria and interatrial septum are
      not well known. Most such lesions do not become clinically significant; however,
      intractable arrhythmias, blood flow obstruction, and valvular disruption may
      result from extensive fatty infiltration of the atrial wall or from the mass
      effect of benign or malignant lipomatous tumors. Some fatty lesions may be
      difficult to characterize radiologically, and misdiagnosis may lead to
      unnecessary surgical interventions. We describe the pathology of the most common
      fatty lesions and underscore some of the radiographic and surgical issues
      pertaining to the diagnosis and management of these masses.

PMID- 16949931
TI  - Low serum level of pro-matrix metalloproteinase 2 correlates with aggressive
      behavior in breast carcinoma.
AB  - Malignant tumors that are capable of invading surrounding structures and
      metastasizing possess certain capacities to cross tissue barriers. Matrix
      metalloproteinases (MMPs), especially gelatinases and their inhibitor molecules,
      are known to affect the extracellular matrix turnover, and the proteolytic
      imbalance due to the abnormal expression of these enzymes eventually leads to
      cancer progression. This has been well documented at the tissue level. In this
      study, the different forms of the circulating MMP-2 have been studied in the
      preoperative sera of 71 patients with breast carcinoma. A quantitative enzyme
      linked immunosorbent assay was performed for total proMMP-2, proMMP-2-tissue
      inhibitor of metalloproteinase 2 (TIMP-2) complex, and free active MMP-2. It is
      shown here, for the first time, that the total proMMP-2 levels in the serum
      correlate inversely with node positivity, high stage of the disease, and high
      nuclear grade of the breast tumor. An association with the levels of lower free
      active MMP-2 and tumor recurrence is also demonstrated. Interestingly, the tumor
      tissue expression of MMP-2 had an inverse correlation with proMMP-2-TIMP-2
      complex levels in the serum. In conclusion, the levels of the total proMMP-2
      correlate inversely with tumor burden, whereas free active MMP-2 might be
      associated with survival. This could indicate that the prognostic value of the
      circulating forms of MMP-2 is not congruent with the prognostic information
      obtained from tissue expression. This is further supported by the inverse
      correlation of the proMMP-2-TIMP-2 complex and MMP-2 tissue expression in the
      tumor. Therefore, the different forms of circulating metalloproteinases need to
      be evaluated further to explore their full potential for clinical use.

PMID- 16949932
TI  - Enteric neuropathology of the terminal ileum in patients with intractable slow
      transit constipation.
AB  - Slow-transit constipation is usually considered a colonic motor disorder.
      However, there is some evidence that abnormalities may be present in locations
      other than the colon. In particular, several studies have reported abnormal motor
      activity of the small bowel in these patients. We evaluated the neuropathological
      aspects of the terminal ileum in patients with slow-transit constipation to see
      whether abnormalities are present that may explain an abnormal motility of the
      small intestine. Specimens of the terminal ileum were obtained from 16 female
      patients (age range, 42-76 years) with slow-transit constipation undergoing
      surgery for intractable symptoms. Fifteen age- and sex-matched controls were used
      for comparison. Histologic and immunohistochemical evaluation of the myenteric
      plexus and the smooth muscle of the proximal ileal resection margin was carried
      out by means of hematoxylin and eosin, trichrome and periodic acid-Schiff stain,
      neuron-specific enolase, S-100, CD117, CD34, anti-alpha-actin, desmin, and
      vimentin antibodies. The patient group displayed a significantly reduced number
      of glial cells, compared with controls, in both the submucosal and the myenteric
      plexus. Only 1 of the 3 populations of interstitial cells of Cajal (that
      associated with the deep muscular plexus) was decreased in patients. No
      differences were found between patients and controls concerning ganglia neurons,
      fibroblast-like cells, enteric neurons, apoptotic phenomena, and smooth muscle.
      Patients with slow-transit constipation display neuropathological abnormalities
      of the terminal ileum to a lesser extent than those we previously found in the
      colon, which might explain the abnormal motor aspects sometimes found in these
      patients.

PMID- 16949933
TI  - Mucin core polypeptide expression in the progression of neoplasia in Barrett's
      esophagus.
AB  - We have previously demonstrated a specific pattern of mucin (MUC) core
      polypeptide expression in Barrett's esophagus (BE) characterized by MUC1 and MUC6
      positivity in goblet cells in a proportion of cases. The aim of this study was to
      determine the pattern of MUC expression associated with the development and
      progression of dysplasia in BE. Endoscopic mucosal biopsies from 35 patients with
      BE (10 with no dysplasia, 6 with indefinite for dysplasia, 12 with low-grade
      dysplasia [LGD], and 7 biopsies with high-grade dysplasia [HGD]) were
      immunostained (ABC method) with antibodies against MUC1, MUC2, MUC3, MUC5AC, and
      MUC6. The extent and pattern of staining for each marker was evaluated in
      intestinalized Barrett's epithelium and in the various grades of dysplasia. For
      cases with dysplasia, staining was evaluated separately in nondysplastic
      epithelium adjacent to (<1 cm) and distant from (>2 cm) areas of dysplasia. In
      nondysplastic BE, MUC1, MUC2, MUC3, MUC5AC, and MUC6 stained 40%, 100%, 100%,
      100%, and 90% of cases, respectively, in goblet or nongoblet columnar epithelium.
      With the progression of dysplasia (from metaplasia to indefinite, LGD and HGD),
      there was a significant decrease in expression of MUC1, MUC2, and MUC3, and
      alterations in the staining patterns of MUC5 and MUC6. In fact, MUC1 and MUC3
      were entirely absent from all cases of HGD. Interestingly, BE-associated
      adenocarcinomas showed an MUC phenotype distinct from that of HGD, with
      expression of MUC1 and MUC3 in 47% and 67% of cases, and expression of MUC1 in a
      membranous pattern. There was no significant difference in MUC staining in
      nondysplastic BE between patients with and without dysplasia. Alterations in MUC
      expression occur in the progression of dysplasia in BE. However, none of these
      markers helps identify a subgroup of patients at increased risk for neoplasia.

PMID- 16949934
TI  - DNA and kinetic heterogeneity during the clonal evolution of adrenocortical
      proliferative lesions.
AB  - Monoclonal adrenocortical lesions show inverse correlation between proliferation
      and apoptosis, with proliferation being the single most important criterion of
      malignancy in adrenal lesions. No study yet has evaluated the variability of
      proliferation regarding the clonal pattern and diagnosis in adrenocortical
      nodular hyperplasias (ACNHs), adrenocortical adenomas (ACAs), and adrenocortical
      carcinomas (ACCs). We studied 69 ACNHs, 64 ACAs, and 23 ACCs (World Health
      Organization criteria) from 156 females. Clonality HUMARA test (from
      microdissected DNA samples), DNA content and proliferation analysis (slide and
      flow cytometry), and mitotic figure (MF) counting/50 high-power fields (HPFs)
      were performed in the same areas. Heterogeneity was assessed by 5cER (percentage
      of nonoctaploid cells with DNA content exceeding 5c) and standard deviation of
      MF/HPF. Statistics included analysis of variance/Student t tests regarding the
      clonal patterns and diagnosis. Polyclonal patterns were observed in 48 of 62
      informative ACNHs and 7 of 56 informative ACAs, and monoclonal in 14 of 62 ACNHs,
      49 of 56 ACAs, and 21 of 21 ACCs, with all hyperdiploid lesions (14 ACCs and 13
      ACAs) being monoclonal. The standard deviation of MF/HPF progressively increased
      in ACNH-ACA-ACC (0.048 +/- 0.076, 0.110 +/- 0.097, 0.506 +/- 0.291, respectively;
      P = .0023), but did not differentiate ACNH/ACA. Only tetraploid percentage (P =
      .0496) and 5cER (P = .0352) distinguished polyclonal (3.64 +/- 2.20 and 0.14 +/-
      0.15) from monoclonal (7.25 +/- 7.52 and 1.00 +/- 1.74) benign lesions.
      Malignancy significantly correlated with a low diploid percentage and high
      tetraploid percentage. Cell kinetic heterogeneity is the hallmark of
      adrenocortical neoplasms: tetraploid/hypertetraploid cell accumulation
      characterizes monoclonal lesions (suggesting nondisjunctional mitoses), whereas
      heterogeneously distributed mitotic figures and decreased diploid percentage
      define ACCs.

PMID- 16949935
TI  - Progression in melanoma is associated with decreased expression of death
      receptors for tumor necrosis factor-related apoptosis-inducing ligand.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis
      in melanoma by interaction with death receptors TRAIL-R1 (DR4) or TRAIL-R2 (DR5)
      on melanoma cells or resists apoptosis by interaction with decoy receptors TRAIL
      R3 (DcR1) or TRAIL-R4 (DcR2). Studies on cell lines suggest that there is a wide
      variation in TRAIL death receptor expression; however, their expression on
      excised human melanoma is not well documented. In view of this, we studied death
      receptor expression on melanomas using monoclonal antibodies specific for these
      receptors. Immunohistochemical staining for DR4, DR5, and DcR1/DcR2 was performed
      on formalin-fixed paraffin-embedded sections of 100 cases of primary melanoma,
      metastatic melanoma, and benign nevi. Percentage expressions of DR4 versus DR5 in
      benign nevi, primary melanoma, and melanoma metastases were 40% versus 90%, 69%
      versus 98%, and 55% versus 66%, respectively. There were significant differences
      in the mean percentage of DR5-positive cells between different groups of
      melanocytic lesions. Percent expression was higher in thin (< or =1.0 mm)
      compared with thick primary melanoma (88.9% versus 66.9%), and expression was
      less in subcutaneous metastases (49%) and lymph node metastases (30.6%) (P <
      .005). Expression was also higher in compound nevi (57%) than dysplastic nevi
      (49%). DcR1/DcR2 was found in 75% of benign nevi, 62% of primary melanomas, and
      74% melanoma metastases. The results showed a wide variation in the expression of
      death receptors for TRAIL between and within primary and metastatic melanoma and
      a decreased expression on the thick primary melanoma and metastatic melanoma.
      This suggests that melanoma may not respond to treatment with TRAIL unless given
      with agents that increase the expression of TRAIL death receptors.

PMID- 16949936
TI  - Expression of syndecan-1 (CD138) in nasopharyngeal carcinoma is correlated with
      advanced stage and poor prognosis.
AB  - Nasopharyngeal carcinoma (NPC) is an important Epstein-Barr virus-associated head
      and neck malignancy in Taiwan. Syndecan-1 (CD138) is involved in growth,
      differentiation, invasiveness, and metastatic potential of certain tumors, but
      its expression in NPC has never been studied. In this study, detection of
      expression of syndecan-1 protein and Epstein-Barr virus-encoded latent membrane
      protein-1 (LMP-1) in primary, recurrent, and metastatic NPC specimens in paraffin
      sections was performed by immunohistochemistry. The quantity of syndecan-1
      messenger RNA in tumor cells was investigated by real-time reverse transcriptase
      polymerase chain reaction using laser capture microdissection. The results of
      immunohistochemical staining of syndecan-1 and LMP-1 correlated with
      clinicopathologic features of NPC. Eighteen (20.9%) of 86 primary, 9 (24.3%) of
      37 recurrent, and 15 (44.1%) of 34 metastatic NPC samples were positive for
      syndecan-1, and 37 (43.0%) primary, 18 (48.6%) recurrent, and 12 (35.3%)
      metastatic samples were positive for LMP-1 expression. Primary NPCs with syndecan
      1 protein expression were more frequently associated with advanced clinical
      stages and worse 5-year survival rates than those without (P = .015 and P =
      .0021, respectively). Conversely, the LMP-1 expression did not correlate with
      tumor stage or prognosis but occurred more often in nonkeratinizing carcinoma
      than keratinizing squamous cell carcinoma (unpublished observation). The inverse
      expression of syndecan-1 and LMP-1 was noted in primary NPC specimens (total 4/18
      versus 35/68, P = .05). The reverse transcriptase polymerase chain reaction
      revealed low syndecan-1 messenger RNA levels in both primary and metastatic NPC.
      In conclusion, the protein expression of syndecan-1 in 21% of primary NPC was
      associated with advanced disease and poor prognosis, and the protein expression
      correlated with transcription levels.

PMID- 16949937
TI  - Repetitive, duplicate, and redundant publications: a review for authors and
      readers.
AB  - Repetitive, duplicate, and redundant publications are an important concern in the
      scientific literature. Their occurrence affects science and carries with it
      sanctions of consequence. This editorial provides a brief review of the
      definitions, classifications, impact, sanctions, and prevention strategies
      regarding repetitive, duplicate, and redundant publications.

PMID- 16949939
TI  - Immediate effects on neck pain and active range of motion after a single cervical
      high-velocity low-amplitude manipulation in subjects presenting with mechanical
      neck pain: a randomized controlled trial.
AB  - PURPOSE: The objective of this study is to analyze the immediate effects on neck
      pain and active cervical range of motion after a single cervical high-velocity
      low-amplitude (HVLA) manipulation or a control mobilization procedure in
      mechanical neck pain subjects. In addition, we assessed the possible correlation
      between neck pain and neck mobility. METHODS: Seventy patients with mechanical
      neck pain (25 males and 45 females, aged 20-55 years) participated in this study.
      The lateral gliding test was used to establish the presence of an intervertebral
      joint dysfunction at the C3 through C4 or C4 through C5 levels. Subjects were
      divided randomly into either an experimental group, which received an HVLA
      thrust, or a control group, which received a manual mobilization procedure. The
      outcome measures were active cervical range of motion and neck pain at rest
      assessed pretreatment and 5 minutes posttreatment by an assessor blinded to the
      treatment allocation of the patient. Intragroup and intergroup comparisons were
      made with parametric tests. Within-group effect sizes were calculated using
      Cohen's d coefficient. RESULTS: Within-group changes showed a significant
      improvement in neck pain at rest and mobility after application of the
      manipulation (P < .001). The control group also showed a significant improvement
      in neck pain at rest (P < .01), flexion (P < .01), extension (P < .05), and both
      lateral flexions (P < .01), but not in rotation. Pre-post effect sizes were large
      for all the outcomes in the experimental group (d > 1), but were small to medium
      in the control mobilization group (0.2 < d < 0.6). The intergroup comparison
      showed that the experimental group obtained a greater improvement than the
      control group in all the outcome measures (P < .001). Decreased neck pain and
      increased range of motion were negatively associated for all cervical motions:
      the greater the increase in neck mobility, the less the pain at rest.
      CONCLUSIONS: Our results suggest that a single cervical HVLA manipulation was
      more effective in reducing neck pain at rest and in increasing active cervical
      range of motion than a control mobilization procedure in subjects suffering from
      mechanical neck pain.

PMID- 16949940
TI  - Work-related injuries of doctors of chiropractic in the United States.
AB  - PURPOSE: This study was undertaken to determine the prevalence and types of work
      related injuries among a nationwide sample of chiropractors and to identify
      factors associated with these injuries. METHODS: Using a survey, 1000 randomly
      selected doctors of chiropractic in the United States were asked to record their
      3 most serious injuries. Details were obtained about the type of injury, area of
      the body affected, activity performed at that time, year of practice when the
      injury had occurred, if the doctor had needed to take time off from work, and
      what they had changed as a result of the injury. RESULTS: A total of 422
      responses were obtained (42.2%), yielding 397 usable surveys. One hundred fifty
      nine chiropractors (40.1%) reported experiencing a total of 252 injuries while
      working. Most injuries were classified as soft tissue injuries and occurred while
      either performing (66.7%) or positioning (11.1%) a patient for manipulation. Body
      parts most commonly injured were the wrist/hand/finger (42.9%), shoulder (25.8%),
      and low back (24.6%). The anatomic areas of the patient being manipulated in
      which the doctor was injured were the lumbosacral (37.1%) and thoracic spine
      (21.6%). Shoulder (P < .001) and low back (P < .001) injuries were significantly
      more likely to have been caused by adjustments of the lumbosacral spine with the
      patient in the side-lying position. Most commonly, injuries occurred in the first
      to fifth year of practice (37.3%). Of note, 5.4% of injuries reported occurred
      while attending chiropractic college. CONCLUSION: A high prevalence of upper
      extremity injuries was reported in the group surveyed. These injuries were most
      often related to side-posture manipulation to the lumbar spine. Because most
      injuries occurred early on in the career and required a change in technique,
      greater efforts toward injury prevention education should be aimed toward
      chiropractic students.

PMID- 16949941
TI  - Short and long-term results of connective tissue manipulation and combined
      ultrasound therapy in patients with fibromyalgia.
AB  - OBJECTIVE: The aim of the study was to evaluate the short-term and 1-year follow
      up results of connective tissue manipulation and combined ultrasound (US) therapy
      (US and high-voltage pulsed galvanic stimulation) in terms of pain, complaint of
      nonrestorative sleep, and impact on the functional activities in patients with
      fibromyalgia (FM). METHODS: This is an observational prospective cohort study of
      20 female patients with FM. Intensity of pain, complaint of nonrestorative sleep,
      and impact of FM on functional activities were evaluated by visual analogue
      scales. All evaluations were performed before and after 20 sessions of treatment,
      which included connective tissue manipulation of the back daily, for a total of
      20 sessions, and combined US therapy of the upper back region every other
      session. One-year follow-up evaluations were performed on 14 subjects. Friedman
      test was used to analyze time-dependent changes. RESULTS: Statistical analyses
      revealed that pain intensity, impact of FM on functional activities, and
      complaints of nonrestorative sleep improved after the treatment program (P <
      .05). CONCLUSION: Methods used in this study seemed to be helpful in improving
      pain intensity, complaints of nonrestorative sleep, and impact on functional
      activities in patients with FM.

PMID- 16949942
TI  - Chiropractic users and nonusers: differences in use, attitudes, and willingness
      to use nonmedical doctors for primary care.
AB  - OBJECTIVE: To determine the differences in attitudes and other determinants of
      care-seeking behavior between persons who have used chiropractic services and
      persons who have not. A second objective is to determine the interest in members
      of these 2 groups in choosing nonmedical doctors for providing routine services.
      METHODS: In 1998, a nationwide telephone survey of randomly selected households
      in the United States was done, including 400 adults who have used chiropractic
      services and 400 adults who have not. Survey participants were asked about their
      use, knowledge, and attitudes about chiropractic care, attitudes about personal
      role in health care, current source of obtaining usual and routine care, and
      willingness to consider use of nonmedical doctors as the usual source of such
      care. The analysis compares persons who have used with those who have not used
      chiropractic services by using a chi2 test to determine significance of
      differences between the responses of the 2 groups. A multivariate analysis is
      done of willingness to use alternative providers for routine care. RESULTS:
      Persons who have seen a doctor of chiropractic before have different attitudes
      and preferences about health and health care than others who have never seen a
      doctor of chiropractic. Almost all of persons in both groups have medical doctors
      that they use for routine care, and a sizeable portion of both groups would be
      willing to consider using a nonmedical doctor for this role. Although willingness
      to use a chiropractor in this role is much higher among persons who have used a
      chiropractor before, both groups would prefer physician assistants and nurse
      practitioners to chiropractors in this role. CONCLUSION: For persons
      participating in this survey, unwillingness to accept the idea of a chiropractor
      in a primary care role may be largely due to poor knowledge about chiropractic
      care.

PMID- 16949943
TI  - Comparison of bioenergetic synchronization technique and customary chiropractic
      care for older adults with chronic musculoskeletal pain.
AB  - OBJECTIVE: The aim of the study was to compare the clinical outcomes of 2
      approaches to chiropractic care for patients with chronic musculoskeletal pain.
      Included were the approach most commonly used by doctors of chiropractic
      (diversified technique spinal manipulation) and a nonmanipulative mind-body
      approach (Bioenergetic Synchronization Technique). This clinical experiment
      tested the null hypothesis that there is no clinically or statistically
      significant difference in effect between the 2 approaches. METHODS: The study was
      conducted in the research clinic of the Parker College of Chiropractic. Patients
      were initially recruited by contacting a previously developed pool used for
      studies related to fall prevention in the elderly. Eighty-one patients (74
      females; median age, 66 years) were enrolled and 78 (96%) completed the study.
      The primary end point was the end of a 3-week nontreatment interval after a 4
      week treatment period. An intention-to-treat analysis was used; all patients who
      completed assessments were included whether or not they were compliant with the
      treatment protocol. A sample size of 55 per group was estimated to be necessary
      to detect a clinically significant (6-point) between-group difference in the Pain
      Disability Index (PDI). The primary outcome, the mean between-group difference
      between PDI scores at visit 1 and the exit visit, was tested with a 2-tailed t
      test for independent samples. RESULTS: Mean improvements in the PDI from visit 1
      to the exit visit were 6.9 points in the Bioenergetic Synchronization Technique
      group (n = 40) and 6.4 in the diversified technique group (n = 38); the between
      groups difference was not statistically or clinically significant (95% confidence
      interval, -4.7 to 5.8). CONCLUSIONS: For this particular group of patients, both
      groups demonstrated similar improvement scores on the PDI; the study's null
      hypothesis was not rejected.

PMID- 16949944
TI  - Evaluation of functional and neuromuscular changes after exercise rehabilitation
      for low back pain using a Swiss ball: a pilot study.
AB  - OBJECTIVE: The purpose of this pilot study was to use a multidimensional model to
      evaluate deficits in patients with low back pain (LBP) over the course of a 12
      week rehabilitation program using the Swiss ball. METHODS: A within-subjects,
      repeated-measures design based at the University exercise training clinic was
      used. Twenty patients with chronic nonspecific LBP (12 men, 8 women; symptom
      duration, 4.8 years; 38.8 +/- 12.1 years old; height, 1.76 +/- 0.06 m; weight,
      76.15 +/- 7.21 kg) participated in this study. Self-report measures were the
      Oswestry Disability Index, Visual Analog Scale, Medical Outcomes 12-Item Short
      Form Health Survey, and Self-Efficacy For Exercise Scale. Physiologic measures
      were electromyography measurement of feedforward muscle activation, flexion
      relaxation phenomenon, myoelectric fatigue, endurance capacity measured by the
      Sorenson test, and a modified sit-up test. Individuals performed 12 weeks of
      progressive exercise periodized every 4 weeks using a Swiss ball. Outcome
      measures were assessed at baseline, 4 weeks, 8 weeks, 12 weeks, and at a 3-month
      follow-up. Repeated-measures analysis for variance for time differences and
      regression analysis for variance in Oswestry scores were performed. RESULTS: The
      Oswestry score for self-reported disability significantly decreased over the
      intervention (F(4,14) = 19.456, P < .001). Significant improvements in pain and
      disability maintained to the 3 months of follow-up. There were significant
      changes in perceptions of physical and mental well-being, erector spinae fatigue,
      and flexion relaxation measures. Change in flexion relaxation explained 38% of
      the improvement in Oswestry scores at the 12-week measurement. CONCLUSIONS: This
      study showed that the Swiss ball may be successfully used in a rehabilitation
      context for patients with LBP. This pilot study has used a novel approach to
      assess improvements during a rehabilitation program, which may be used in the
      future to explain differences between different treatment modalities.

PMID- 16949945
TI  - Reversible pelvic asymmetry: an overlooked syndrome manifesting as scoliosis,
      apparent leg-length difference, and neurologic symptoms.
AB  - OBJECTIVE: The objective of this study was to investigate the occurrence of
      pelvic asymmetry in neurologic patients with symptoms not explained by their
      neurologic diagnosis. METHODS: We analyzed 150 consecutive neurologic patients
      referred to physiatric consultation based on their clinical examination findings.
      RESULTS: We observed pelvic asymmetry associated with either C-type or S-type
      scoliosis and apparent leg-length difference in 87% of the patients. Symmetry
      could be reestablished by all patients, although 15% showed immediate or imminent
      relapse. Maintenance of symmetry showed a highly significant (P < .001)
      correlation with improvement in functional ability and reduction of pain as
      evaluated during the last visit to the physiatrist. In the follow-up
      questionnaire, 78% of the patients reported improvement in functional ability and
      reduced pain. CONCLUSIONS: Our results support the view that leg-length
      difference and scoliosis may be more often of reversible nature than previously
      considered. Acquired postural asymmetry of the sacroiliac joint may be a
      neglected cause of several neurologic and other pain-related symptoms that can be
      relieved by a simple and safe treatment.

PMID- 16949946
TI  - Predictors of performance of students from the Canadian Memorial Chiropractic
      College on the licensure examinations of the Canadian Chiropractic Examining
      Board.
AB  - PURPOSE: The purpose of this study was to determine if the Canadian Memorial
      Chiropractic College (CMCC) structured admissions interview and other student
      measures predict success on the Canadian Chiropractic Examining Board (CCEB)
      examinations. METHODS: An independent researcher combined CMCC and CCEB data by
      student name and then anonymized the data and destroyed the linking information.
      Backward stepwise multiple linear regressions were applied to external dependent
      variables from the CCEB and internal independent variables from the CMCC.
      RESULTS: Forty percent of the variance in the basic science examination (R2 =
      0.405) was explained by the independent variables of third year objective
      structured clinical examination practical and second-year grade point average
      (chi rhoGPA). Forty-five percent of the variance in the applied science
      examination (R2 = 0.448) was explained by the fourth year final examination and
      chi rhoGPA for years 4, 2, and 3. Twenty-four percent of the variance in the
      clinical decision making examination (R2 = 0.239) was explained by chi rhoGPAs of
      years 4, 1, 2, and 3. Sixteen percent of the variance in the clinical skills
      examination (R2 = 0.160) was explained by the third year objective structured
      clinical examination theory and chi rhoGPA for year 2. CONCLUSION: For this
      educational institution, the admissions interview is not a predictor of success
      on the outcome measures of the CCEB. Student chi rhoGPA in year 2 is critical to
      success on CCEB licensure examinations. This information infers that students
      should only continue in their education after they have demonstrated a mastery
      level at the end of year 2.

PMID- 16949947
TI  - Coupling behavior of the cervical spine: a systematic review of the literature.
AB  - OBJECTIVE: The purpose of this study was to investigate evidence of consistency
      of reported directional coupling patterns among selected studies and to determine
      its use in manual medical treatment. METHODS: The study was a systematic
      literature review of English-only journals using PubMed and CINAHL. The keywords
      included "cervical vertebrae," "biomechanics," "coupling," and "three-dimensional
      movement" and required coupling directional assessment of individual spine
      segments. RESULTS: Four 2-dimensional and 8 3-dimensional studies met inclusion
      criteria. This study found 100% agreement in coupling direction (side flexion and
      rotation to the same side) in lower cervical vertebral segments (C2-3 and lower)
      and variation in coupling patterns in the upper cervical segments of occiput-C1
      (during side flexion initiation) and C1-2. Dissimilarities may be explained by
      differences in measurement devices, movement initiation, in vivo vs in vitro
      specimens, and anatomical variations. CONCLUSIONS: These findings suggest that
      use of 3-dimensional analyzed cervical coupling patterns for the lower cervical
      vertebral during apposition and treatment application may show clinical use for
      manual clinicians. The use of directional coupling based on 2-dimensional
      cervical coupling patterns or upper cervical spine coupling that addresses C1-2
      should be questioned.

PMID- 16949948
TI  - Inconsistent grading of evidence across countries: a review of low back pain
      guidelines.
AB  - OBJECTIVE: The aim of this study was to report clinical treatment recommendations
      for low back pain (LBP) based on 5 international guidelines and best evidence
      from the Cochrane database of systematic reviews. METHODS: Five LBP guidelines
      available in English language were appraised, including 4 studies published since
      the seminal work by Koes et al (Spine 2001;26:2504-5213). The guidelines were
      examined for treatment recommendations concerning nonspecific LBP and guideline
      quality with application of the Appraisal of Guidelines for Research and
      Evaluation instrument. Secondly, a systematic literature search for reviews and
      randomized controlled trials was conducted using a modified version of the search
      strategy recommended by the Cochrane Back Review Group. Two systematic reviews
      were identified. RESULTS: According to best evidence from review of the Cochrane
      database of systematic reviews, there remains a lack of consensus regarding
      reported efficacy of spinal manipulative therapy for the treatment of nonspecific
      LBP. Furthermore, the guidelines reviewed in the present study have not changed
      significantly with respect to treatment recommendations for nonspecific LBP since
      the original review, and there is inconsistency between the guidelines regarding
      optimal time to introduce spinal manipulation to treat nonspecific LBP.
      CONCLUSION: Treatment recommendations for nonspecific LBP, particularly spinal
      manipulation, remain inconclusive. Guideline developers need to consider
      guidelines in neighboring countries and reach consensus on how evidence is graded
      and incorporated into guidelines. Guidelines should continue to be regularly
      updated to incorporate new evidence and methods of grading the evidence.

PMID- 16949949
TI  - Spinal epidural hematoma after spinal manipulative therapy in a patient
      undergoing anticoagulant therapy: a case report.
AB  - OBJECTIVE: We report on the case of a patient with spinal epidural hematoma (SEH)
      after spinal manipulative therapy and review features of reported cases of a
      similar nature. CLINICAL FEATURES: The patient was undergoing Coumadin
      anticoagulant therapy for atrial fibrillation and presented to the chiropractor
      complaining of a stiff neck. After cervical manipulation, he developed
      paresthesia in both feet, progressing to motor deficits in all 4 extremities. He
      required a laminectomy and evacuation of a clot indenting the spinal cord.
      RESULTS: Review of the literature revealed 7 reported cases of SEH after
      manipulation; 5 patients underwent cervical manipulation and 1 patient received
      Coumadin therapy. CONCLUSION: Practitioners of spinal manipulative therapy should
      be aware of SEH as a possible complication of manipulation in patients at risk
      and should exercise caution in the care of patients undergoing anticoagulant
      therapy.

PMID- 16949950
TI  - A case report of an unstable cervical spine fracture: parallels to the
      thoracolumbar chance fracture.
AB  - OBJECTIVE: To discuss the case of a 40-year-old woman who had a cervical spine
      fracture similar in appearance to a Chance fracture and to discuss its
      radiographic appearance. CLINICAL FEATURES: A 40-year-old woman sought
      chiropractic care for neck pain and weakness in both arms after a motor vehicle
      accident. Neck flexion worsened the weakness in her upper extremities, her
      radiating neck pain, and upper extremity pain. A transverse fracture through the
      spinous process of C6 and narrowed C6 disk space was noted on plain film
      radiographs. Magnetic resonance imaging findings were consistent with a large
      midline extruded disk herniation at the C6-7 level with marked extrinsic
      compression on the cervical cord in addition to the fracture. These findings were
      similar to a lumbar spine Chance fracture. INTERVENTION AND OUTCOME: The patient
      was referred for surgical consultation, and discectomy with fusion of C6-7 was
      performed. After the surgery, the upper extremity pain and weakness subsided.
      Postsurgical care included chiropractic adjustments with a handheld spring-loaded
      adjusting instrument and physiotherapy. CONCLUSION: The radiographic features of
      an unusual cervical spine fracture with the characteristics of a Chance-type
      fracture are discussed.

PMID- 16949951
TI  - First rib fracture of unknown etiology: a case report.
AB  - OBJECTIVE: The purpose of this study is to describe the case of a patient with a
      first rib fracture discovered with advanced imaging once the patient did not
      respond to an initial course of care. CLINICAL FEATURES: A 24-year-old otherwise
      healthy male electrician had medial scapular, upper thoracic, and sternal pain
      while using a power drill in the overhead position. INTERVENTION AND OUTCOME: An
      initial trial of treatments consisting of spinal manipulation and modalities
      failed to alleviate the patient's symptoms. Chiropractic treatment was
      discontinued and further diagnostic testing with advanced imaging was performed.
      Once the pathology was identified, the patient was placed on light duty at work
      with restrictions limiting overhead activities. No other treatment was rendered.
      The patient was symptom-free approximately 10 months after the onset of pain.
      CONCLUSIONS: Patients with complaints of spine and scapular pain may commonly
      present to a chiropractor for care. When these types of symptoms do not respond
      to conservative therapy, other causes should be investigated. In this case, the
      patient's symptoms resulted from a nontraumatic fracture of the first rib. First
      rib fractures should be considered in the differential diagnosis of patients with
      upper quadrant pain that is not responsive to conservative care.

PMID- 16949952
TI  - Stress-induced spiculated periosteal reaction appearing as a malignant bone
      tumor: a case report.
AB  - OBJECTIVE: The aim of this study was to describe the appearance of a rare
      occurrence of a spiculated periosteal reaction caused by stress injury and the
      subsequent diagnostic assessments. A proposed mechanism for the etiology of
      stress-induced periosteal reactions in this case is offered. CLINICAL FEATURES: A
      54-year-old female had ankle pain for 1 year. Radiographs revealed a spiculated
      periosteal reaction of the distal fibula. In light of the clinical history of
      prior breast carcinoma, the possibility of metastatic disease was entertained.
      INTERVENTION AND OUTCOME: Scintigraphy and magnetic resonance imaging were used
      in the diagnostic evaluation of this patient. Malignancy was ruled out on the
      basis of the magnetic resonance imaging findings, and an etiology of a stress
      reaction was proposed based on the scintigraphic findings. CONCLUSION: Stress
      induced spiculated periosteal reactions are a rare occurrence. This case
      illustrates the role that advanced imaging plays in the assessment of a
      suspicious periosteal reaction.

PMID- 16949953
TI  - Adverse reactions to chiropractic care in the UCLA Neck Pain Study.

PMID- 16949956
TI  - Inhibition of ribonuclease and protease activities in arsenic exposed rice
      seedlings: role of proline as enzyme protectant.
AB  - When seedlings of two rice (Oryza sativa L.) cvs. Malviya-36 and Pant-12 were
      raised under 25 and 50 microM As2O3 in the medium an increase in the level of
      RNA, proteins and proline accompanied with a decline in the level of free amino
      acid pool was observed under arsenic supplementation compared to controls. In
      situ As3+ treatment caused a marked inhibition in activities of ribonuclease
      (RNase, EC 3.1.27.1), protease and leucine aminopeptidase (LAP, EC 3.4.11.1)
      whereas the activity level of carboxypeptidase (EC 3.4.16.5) was enhanced. In
      vitro supply of As2O3 in the enzyme assay medium beyond 400 microM resulted in
      gradual inhibition of RNase and beyond 5 microM inhibition of LAP activities.
      Addition of 1M proline in the assay medium significantly restored the loss in
      RNase activity due to in vitro arsenic treatment or due to osmotic stress created
      by incorporation of polyethylene glycol (PEG). Isoform pattern of RNase extracted
      from As3+ -exposed seedlings showed a significant alteration compared to its
      pattern in unexposed seedlings. Results suggest that arsenic exposure impairs
      hydrolysis of RNA and proteins in rice seedlings due to inhibition of RNase and
      proteases activities and that proline accumulating under As3+ toxicity appears to
      serve as enzyme protectant.

PMID- 16949955
TI  - Suppression of phospholipase Dalpha1 induces freezing tolerance in Arabidopsis:
      response of cold-responsive genes and osmolyte accumulation.
AB  - Phospholipase D (PLD; EC 3.1.4.4) plays an important role in membrane lipid
      hydrolysis and in mediation of plant responses to a wide range of stresses.
      PLDalpha1 abrogation through antisense suppression in Arabidopsis thaliana
      resulted in a significant increase in freezing tolerance of both non-acclimated
      and cold-acclimated plants. Although non-acclimated PLDalpha1-deficient plants
      did not show the activation of cold-responsive C-repeat/dehydration-responsive
      element binding factors (CBFs) and their target genes (COR47 and COR78), they did
      accumulate osmolytes to much higher levels than did the non-acclimated wild-type
      plants. However, a stronger expression of COR47 and COR78 in response to cold
      acclimation and to especially freezing was observed in PLDalpha1-deficient
      plants. Furthermore, a slower activation of CBF1 was observed in response to cold
      acclimation in these plants compared to the wild-type plants. Typically, cold
      acclimation resulted in a higher accumulation of osmolytes in PLDalpha1-deficient
      plants than in wild-type plants. Inhibition of PLD activity by using
      lysophosphatidylethanolamine (LPE) also increased freezing tolerance of
      Arabidopsis, albeit to a lesser extent than did the PLD antisense suppression.
      Exogenous LPE induced expression of COR15a and COR47 in the absence of cold
      stimulus. These results suggest that PLDalpha1 plays a key role in freezing
      tolerance of Arabidopsis by modulating the cold-responsive genes and accumulation
      of osmolytes.

PMID- 16949957
TI  - Growth and cellular ion content of a salt-sensitive symbiotic system Azolla
      pinnata-Anabaena azollae under NaCl stress.
AB  - Salinity, at a concentration of 10 mM NaCl affected the growth of Azolla pinnata
      Anabaena azollae association and became lethal at 40 mM. Plants exposed up to 30
      mM NaCl exhibited longer roots than the control, especially during the beginning
      of incubation. Average root number in plants exposed to 10 and 20 mM NaCl
      remained almost the same as in control. A further rise in NaCl concentration to
      30 mM reduced the root number, and roots shed off at 40 mM NaCl. Presence of NaCl
      in the nutrient solution increased the cellular Na+ of the intact association
      exhibiting differential accumulation by individual partners, while it reduced the
      cellular Ca2+ level. However, cellular K+ content did not show significant
      change. Cellular Na+ based on fresh weight of respective individual partners
      (host tissues and cyanobiont) remained higher in the host tissues than the
      cyanobiont, while reverse was true for K+ and Ca2+ contents. The contribution of
      A. azollae in the total cellular ion content of the association was a little
      because of meagre contribution of the cyanobiont mass (19-21%). High salt
      sensitivity of Azolla-Anabaena complex is due to an inability of the association
      to maintain low Na+ and high Ca2+ cellular level.

PMID- 16949958
TI  - Study of the temperature effect in three chestnut (Castanea sativa Mill.)
      cultivars' behaviour.
AB  - The aim of this work was to analyse the effect of temperature in three chestnut
      cultivars, Aveleira, Judia and Longal. For this purpose, gas exchange, thylakoid
      membrane potential, photosynthetic pigment and lipid content data in July,
      September and October under different temperatures (31, 26 and 18 degrees C) were
      determined. With respect to gas exchanges, significant changes in photosynthesis
      rate of Aveleira were observed between July and September (7mumol CO2m(-2)s(-1)).
      In contrast, Judia and Longal showed a strong increase in this period, 6.1-8.5
      and 4.9-6.7 micromol CO2m(-2)s(-1), for Judia and Longal, which represent an
      increase of about 15% and 43%, respectively. Similar patterns were detected in
      daylight photosynthesis measurements for Judia and Longal, in which an almost 60%
      decrease was observed, in contrast to 40% for Aveleira, from morning to midday,
      when temperatures increased from 27 to 34 degrees C. In addition to high
      photosynthetic rates in the hottest month, Aveleira was also the sunniest
      cultivar according its highest value on chlorophyll a/b ratio (3.65). Cultivars
      also presented maximal thylakoid membrane potential at different temperatures,
      with their values being 20.8, 17.8 and 17.2 degrees C for Aveleira, Longal and
      Judia, respectively. These results were also supported by thylakoid fatty acid
      composition which indicated that the unsaturation index of Aveleira (158) was the
      lowest in comparison with other two cultivars, 168 and 175, for Longal and Judia,
      respectively.

PMID- 16949959
TI  - Cloning and expression analysis of two beta-1,3-glucanase genes from strawberry.
AB  - We isolated from strawberry (Fragariae x ananassa Duch) a genomic clone of a beta
      1,3-glucanase gene, designated as FaBG2-2. In addition, a related cDNA clone,
      designated as FaBG2-3, was also isolated. FaBG2-2 and FaBG2-3 are similar in
      their coding regions, except that FaBG2-2 does not appear to contain a signal
      peptide coding sequence. The 5' and 3' flanking regions of FaBG2-2 and FaBG2-3
      are differentt. Using real-time PCR, the expression patterns of FaBG2-3 and a
      previously isolated beta-1,3-glucanase gene, FaBG2-1, in strawberry plants
      infected with Colletotrichum fragariae or Colletotrichum acutatum were analyzed
      at different time points post-infection. The results showed that expressions of
      both genes in the leaves of infected plants were induced by the two fungi, but
      the level of induction was several fold greater with C. fragariae. Comparison of
      the expression levels of the two genes revealed that the level of FaBG2-3
      expression was several hundred to over a thousand fold higher than that of FaBG2
      1. Furthermore, the expression levels of the two genes in the leaf, fruit, crown
      and root of uninfected strawberry plants were analyzed.

PMID- 16949961
TI  - Ferritin2 gene in paraquat-susceptible and resistant biotypes of horseweed Conyza
      canadensis (L.) Cronq.
AB  - Ferritins, the multimeric iron storage proteins, are the main regulators of the
      cellular level of uncomplexed iron. Ferritins are encoded by small gene families
      and expressed differentially under various developmental conditions depending on
      iron availability, effect of hormones or oxygen radical generating agents. In the
      present work the primary structure of the ferritin2 gene from resistant and
      susceptible biotypes of horseweed Conyza canadensis was determined. This gene was
      found to exhibit great similarity and possess all the structural characteristics
      of known plant ferritin2 genes. The C. canadensis ferritin2 genes had identical
      primary structure in the two biotypes and were upregulated by paraquat (Pq) in
      both susceptible and resistant plants. The enhanced expression level was probably
      connected with defence reactions in the plants after Pq treatment.

PMID- 16949960
TI  - Molecular cloning and stress-dependent regulation of potassium channel gene in
      Chinese cabbage (Brassica rapa ssp. Pekinensis).
AB  - Potassium channels are important for many physiological functions in plants, one
      of which is to regulate plant adaption to stress conditions. In this study, KCT2,
      the gene encoding a membrane-bound protein potassium channel (GenBank accession
      number: ), was isolated from Chinese cabbage (Brassica rapa ssp. Pekinensis) by
      RACE-PCR technique. Bioinformatics methods were performed for the gene structure
      and molecular similarity analysis. The KCT2 expression patterns under various
      stress conditions were studied by semi-quantitative RT-PCR. DNA gel blot was used
      to analyze genomic organization. The putative KCT2 was found to contain five
      membrane-spanning segments, a pore-forming domain (P-domain) between the last two
      transmembrane spans, a TxxTxGYGD motif in the P-domain and a putative cyclic
      nucleotide-binding-like domain within a long C-terminal region. KCT2 is closest
      to KAT2 in Arabidopsis. KCT2 could be a one-copy gene with different isoforms or
      belong to a small gene family with four or five members. KCT2 was expressed more
      strongly in leaves than in shoots and roots. KCT2 transcription products were up
      regulated by a 4-h-incubation in abscisic acid (ABA) and various stress treatment
      including cold stress (4 degrees C) for 24 h, drought stress for 1h, and salt
      stress for 12 h. KCT2 transcription was not affected by anoxia stress for 8h and
      was down-regulated with cold stress for 48 h. KCT2 was cloned for the first time
      from the genus Brassica. Expression analysis indicated that in the early stage of
      plant adaption to stress conditions KCT2 is up-regulated, which results in a
      stimulation of potassium transport.

PMID- 16949962
TI  - Acute bacterial rhinosinusitis: a review of U.S. treatment guidelines.
AB  - Acute bacterial rhinosinusitis (ABRS) is a common complication of viral upper
      respiratory tract infections and is associated with a significant socioeconomic
      burden. Guidelines for the diagnosis and management of ABRS have been produced in
      association with a number of societies in the United States; these guidelines aim
      to promote the rational selection of antibiotic therapy to optimize clinical
      outcomes while minimizing the potential for selection of antibiotic resistance.
      This article provides an overview of current U.S. guidelines for the treatment of
      ABRS, focusing on the impact of antibiotic resistance on treatment options.

PMID- 16949963
TI  - Sinusitis of odontogenic origin.
AB  - Odontogenic sinusitis is a well-recognized condition and accounts for
      approximately 10% to 12% of cases of maxillary sinusitis. An odontogenic source
      should be considered in individuals with symptoms of maxillary sinusitis with a
      history of odontogenic infection, dentoalveolar surgery, periodontal surgery, or
      in those resistant to conventional sinusitis therapy. Diagnosis usually requires
      a thorough dental and clinical evaluation including appropriate radiographs. The
      most common causes of odontogenic sinusitis include dental abscesses and
      periodontal disease that had perforated the Schneidarian membrane, irritation and
      secondary infection caused by intra-antral foreign bodies, and sinus perforations
      during tooth extraction. An odontogenic infection is a polymicrobial aerobic
      anaerobic infection, with anaerobes outnumbering the aerobes. The most common
      isolates include anaerobic streptococci and gram-negative bacilli, and
      Enterobacteriaceae. Surgical and dental treatment of the odontogenic pathological
      conditions combined with medical therapy is indicated. When present, an
      odontogenic foreign body should be surgical removed. Surgical management of
      oroantral communication is indicated to reduce the likelihood of causing chronic
      sinus disease. The management of odontogenic sinusitis includes a 3- to 4-week
      course of antimicrobials effective against the oral flora pathogens.

PMID- 16949964
TI  - Current management of penetrating injuries of the soft palate.
AB  - Children present to emergency departments with soft palate impalement injuries on
      an infrequent though periodic basis. Although these usually heal without
      treatment, internal carotid artery thrombosis occurs on rare occasions due to
      vessel compression causing intimal disruption. Thirty-two cases have been
      reported in the English literature. Hospital observation for up to 72 hours had
      been recommended previously for all of these injuries because of a "lucid
      interval," usually present before onset of neurologic symptoms. Subsequent
      studies have shown a very low occurrence of carotid injury and support outpatient
      observation similar to that after minor head injury. This is further justified by
      the lack of evidence that any diagnostic study or therapeutic measure alters the
      ultimate prognosis and outcome. Laceration repair is suggested for retained
      foreign bodies, through and through injury, or if a large hanging flap is
      present. Antibiotic indications are not well defined but should be considered for
      lacerations over 1 to 2 cm in length.

PMID- 16949965
TI  - Research education and training in otolaryngology: meeting summary and research
      opportunities.

PMID- 16949966
TI  - Does the chorda tympani nerve confer general sensation from the tongue?
AB  - OBJECTIVE: Patients often complain of numbness of the tongue after otologic
      procedures; this symptom may occur with or without taste alterations. The purpose
      of this study was to objectively assess possible changes in the general sensation
      of the tongue in patients undergoing middle ear surgery. STUDY DESIGN AND
      SETTING: Thirty-three individuals were included in this prospective controlled
      clinical study conducted at a tertiary referral center. Fifteen patients
      underwent middle ear surgery and 18 volunteers served as a control group.
      Subjects underwent objective tests to assess general sensation of the tongue
      before and twice after surgery. RESULTS: Forty-seven percent of the patients
      complained of numbness or tingling of the tongue shortly after surgery. In these
      patients, a significant reduction in sensitivities to light touch and 2-point
      discrimination on the operated side were noted at that time (P < 0.01; P < 0.009
      respectively). Values returned to baseline on subsequent evaluations. No
      sensitivity change was noted for the contralateral hemi-tongue. CONCLUSION:
      Objective changes in the general sensory function of the tongue correlated with
      post-operative clinical symptoms experienced by patients. The results of this
      study support the notion that the chorda tympani nerve confers general sensation
      from the tongue. EBM RATING: A-1b.

PMID- 16949967
TI  - Impact of electrode insertion depth on intracochlear trauma.
AB  - OBJECTIVE: To assess the effect of cochlear implant (CI) insertion depth and
      surgical technique on intracochlear trauma. STUDY DESIGN AND SETTING: Twenty-one
      fresh human temporal bones were implanted with CI electrodes and underwent
      histologic processing and evaluation. Specimens were grouped into 3 categories:
      1) soft implantation technique and standard electrode; 2) soft implantation
      technique and flexible prototype array; 3) forceful implantations and standard
      electrode. Based on the grading system (1 to 4), 2 numeric values were calculated
      indicating the overall severity of cochlear damage (trauma indices). RESULTS:
      Mean trauma index values were 13.8, 36.3, and 59.2 for group 1, 2, and 3,
      respectively. Differences in cochlear trauma (trauma index) were nonsignificant
      between specimens in groups 1 and 2 but were significant between groups 1 and 3.
      CONCLUSION: This study gives evidence that intracochlear trauma increases with
      deep insertions. Thus, in cases where cochlear integrity might be important,
      limited insertions should be achieved.

PMID- 16949968
TI  - Complication rate of minimally invasive cochlear implantation.
AB  - OBJECTIVES: To assess the complication rate of minimally invasive cochlear
      implantation (MICI). STUDY DESIGN AND SETTING: Data for this study were obtained
      via a retrospective analysis of records at the Ear Medical Group, San Antonio,
      TX, after IRB approval at the University of Texas Health Science Center at San
      Antonio. The surgical complications of MICI were recorded in a spreadsheet
      format; 176 patients were included in the study. RESULTS: A total of 22 (12.5%)
      complications were noted in the study. There were 0 life-threatening, 7 major,
      and 15 minor complications. Of the 7 major complications, 3 were device failures,
      2 developed delayed mastoiditis, 1 required receiver/stimulator repositioning,
      and 1 involved facial paralysis. CONCLUSIONS: MICI is as safe as standard
      cochlear implantation (SCI) and affords with it other benefits. Eliminating the
      scalp flap avoids devascularization and minimizes the opportunity of flap
      infection or necrosis. Complications not related to the flap are similar to SCI.
      EBM RATING: C-4.

PMID- 16949969
TI  - Split-thickness skin grafting in postmastoidectomy revision and in lateral
      temporal bone resection.
AB  - OBJECTIVES: Use of split-thickness skin grafts (STSG) in revision canal wall-down
      (CWD) mastoidectomy was compared with STSG in lateral temporal bone resection
      (LTBR). STUDY DESIGN AND SETTING: A retrospective study of 11 patients undergoing
      revision CWD mastoidectomy and 6 patients undergoing LTBR with STSG in an
      academic health center setting. RESULTS: Successful epithelialization of the
      mastoid cavity occurred in 9 patients (82%) undergoing CWD mastoidectomy.
      Subjective success, measured as reduction in complaints of otorrhea, occurred in
      10 patients (91%). In the 6 patients who underwent LTBR and STSG successful
      epithelialization of the temporal bone defect occurred in 5 patients (83%).
      CONCLUSIONS: Successful and rapid epithelialization occurred in the revision
      mastoidectomy cohort as well as in the primary temporal bone resection cohort.
      SIGNIFICANCE: Placement of STSG is a useful adjunct in revision CWD mastoidectomy
      as well as in primary LTBR for cancer.

PMID- 16949970
TI  - Unusual Corynebacterium mucifaciens isolated from ear and nasal specimens.
AB  - OBJECTIVE: Corynebacterium mucifaciens was first proposed as a novel
      Corynebacterium species in 1997. This report describes our experience with the
      unexpectedly frequent isolation of C mucifaciens. STUDY DESIGN: By using agar
      supplemented with several antibiotics, microbiological studies were performed on
      specimens collected from the ear and nose. SETTING: A primary and secondary
      referral hospital. RESULTS: The organisms grew slowly. Five strains of C
      mucifaciens were found in specimens of middle ear effusion (MEE) from patients
      with otitis media with effusion (OME), and four strains were isolated from the
      nasal polyps and nasal discharge of patients with chronic sinusitis (CRS).
      CONCLUSIONS: C mucifaciens was isolated from nine otorhinological specimens.
      SIGNIFICANCE: This is the first report about the isolation of C mucifaciens from
      MEE, nasal polyps, and nasal discharge. Although its pathogenetic role is
      unknown, the characteristics of this microorganism might make it a potential
      cause of OME and/or CRS, so further studies are necessary. EBM RATING: C-4.

PMID- 16949971
TI  - Human serum for tissue engineering of human nasal septal cartilage.
AB  - OBJECTIVE: To compare the chondrogenic and proliferative effects of pooled human
      serum (HS) and fetal bovine serum (FBS) on tissue-engineered human nasal septal
      chondrocytes. STUDY DESIGN AND SETTING: Human chondrocytes were expanded for one
      passage in monolayer in medium supplemented with 10% FBS, 2% HS, 10% HS, or 20%
      HS. Cells were then suspended in alginate beads for 3D culture for 2 weeks with
      10% FBS, 2% HS, 10% HS, or 20% HS. RESULTS: Monolayer cell yields were greater
      with HS than FBS. In alginate, cellular proliferation, glycosaminoglycan
      production per cell, and type II collagen were significantly higher with 10% HS
      compared to 10% FBS controls. CONCLUSION: HS results in increased proliferation
      and production of cartilaginous extracellular matrix by tissue-engineered human
      nasal septal chondrocytes, compared to FBS controls. SIGNIFICANCE: Culture with
      human serum may facilitate creation of neocartilage constructs that more closely
      resemble native tissue.

PMID- 16949972
TI  - CT analysis and histopathology of bone remodeling in patients with chronic
      rhinosinusitis.
AB  - OBJECTIVE: To evaluate the findings of computed tomography (CT) and
      histopathology of the bulla ethmoidalis as objective markers of bone remodeling
      in chronic rhinosinusitis (CRS). METHODS: Preoperative ostiomeatal unit (OMU)
      scans and histopathologic findings of the bulla ethmoidalis were performed on 23
      patients (39 sides) undergoing endoscopic sinus surgery for CRS. Lund-Mackay
      scores and Hounsfield units (HU) of the bulla were checked in coronal CT scans.
      The pathologist graded the severities of the mucosal and bony changes in
      histopathology. Statistical analysis was performed using Mann-Whitney U test and
      Spearman correlation coefficient (r). RESULTS: The HU values of the bulla were
      significantly increased with higher Lund-Mackay scores in OMU CT (r = 0.405, P =
      0.01). The bony grades in histopathology were significantly increased with higher
      mucosal grades (r = 0.821, P = 0.0001). These findings in CT scans and
      histopathology were well correlated with each other (r > 0.3, P < 0.05).
      CONCLUSION: HU may be a useful objective marker of bone remodeling in chronic
      rhinosinusitis.

PMID- 16949973
TI  - Radiation dosimetry of the FluoroCAT scan for real-time endoscopic sinus surgery.
AB  - OBJECTIVE/HYPOTHESIS: The FluoroCAT platform of the GE InstaTrak 3500 Plus
      reconstructs images acquired from the GE OEC 9800 Plus fluoroscope into triplanar
      images which allow the surgeon to perform real-time endoscopic sinus and skull
      base surgery. The radiation dosimetry for the new scanning protocol required by
      the FluoroCAT has not been reported. This study was designed to measure the
      radiation dose of a FluoroCAT scan and compare this to the dosimetry of an
      InstaTrak CT scan. STUDY DESIGN: Prospective study. METHODS: A standardized CT
      head phantom was used along with a CT ion chamber to measure radiation exposure.
      FluoroCAT scans were performed using the GE OEC 9800 Plus fluoroscope. Scans were
      performed using each of the three fluoroscopic scanning modes on the GE OEC 9800
      Plus; normal fluoro, high-level fluoro, and Digital Cine at 15 pulses per second
      (pps). RESULTS: The highest radiation dose was measured using Digital Cine 15
      pps. The dose measured at the center of the head phantom was 4.1 Gy while the
      maximum surface dose was 10.7 mGy. The center and surface radiation dose recorded
      from the CTDI(vol) reading on the control panel of a GE Lightspeed Plus during an
      InstaTrak CT scan was 85 mGy. CONCLUSIONS: Using the GE OEC 9800 Plus fluoroscope
      to accumulate images for the FluoroCAT platform in the InstaTrak 3500 Plus
      resulted in less radiation compared to an InstaTrak CT scan. This will allow
      multiple scans to be performed intraoperatively, giving the surgeon the
      opportunity to perform real-time endoscopic sinus and skull-base surgery. EBM
      RATING: C-4.

PMID- 16949974
TI  - Use of anteriorly based pericranial flap in frontal sinus obliteration.
AB  - OBJECTIVE: In an era of endoscopic sinus surgery, frontal sinus obliteration
      continues to remain an important treatment option in chronic frontal sinus
      disease. Numerous avascular obliterative materials including fat, muscle,
      cancellous bone, and hydroxyapatite have been used in this procedure. In this
      article, we describe a vascularized anteriorly based pericranial flap to
      obliterate frontal sinus. STUDY DESIGN: Retrospective chart review of patients
      referred to tertiary care hospital between 1996 and 2003. METHODS: Records of the
      patients who underwent this procedure were reviewed. Demographics, indications,
      and immediate and late complications were recorded. A phone questionnaire was
      used to assess patient satisfaction with the outcome. RESULTS: A total of 12
      patients underwent frontal sinus obliteration with this technique. Mean follow-up
      was 40 months. None of the patients developed recurrent frontal sinusitis. All of
      the patients were pleased with the outcome. CONCLUSION: Pericranial flap is a
      highly vascularized flap that is easily harvested and is an effective and viable
      modality for obliterating frontal sinus. EBM RATING: C-4.

PMID- 16949975
TI  - Acoustical analysis of snoring: can the probability of success be predicted?
AB  - PURPOSE: Palatal flutter snoring is the most common form of snoring. However,
      other types of snoring do exist. Does identifying palatal snoring beforehand
      translate into improved subjective treatment success with palatal stiffening
      procedures? METHODS: Fifty-three patients presenting with snoring were evaluated
      with a commercially available device. The proportion (%) and magnitude of palatal
      flutter (dB) were quantified. Patients then underwent a palatal stiffening
      procedure and subjective success/failure was assessed. RESULTS: Overall
      subjective treatment success was 85% (45 of 53). The percent palatal flutter was
      the most predictive of success (area under ROC = 0.8556, 95% CI = .7428-.9683).
      Patients exceeding 68% palatal flutter had a 95% (39 of 41) success rate (P =
      0.001, Fisher's exact) and an adjusted odds ratio of treatment success of 25.2
      (95% CI = 3.22-196, P = 0.002). CONCLUSION: Palatal stiffening treatments are
      successful in the majority of patients. However, identifying patients with
      predominant palatal flutter snoring significantly increases the probability of
      subjective treatment success. EBM RATING: B-2b.

PMID- 16949976
TI  - Generic and specific quality-of-life measures in Taiwanese adults with sleep
      disordered breathing.
AB  - OBJECTIVE: To investigate the quality-of-life status of Taiwanese adult patients
      with sleep-disordered breathing (SDB). STUDY DESIGN AND SETTING: A prospective,
      quality-of-life survey in a tertiary referral sleep center on 94 consecutive
      adult SDB patients. Patients were evaluated with polysomnogram, Medical Outcome
      Study SF-36 Health Survey, Snore Outcome Survey (SOS), and Epworth Sleepiness
      Scale (ESS). RESULTS: SDB patients have significantly lower scores in all 8 SF-36
      subscales (P < 0.05) than do normative Taiwan adult population. Apnea patients
      have lower SOS (34.5 +/- 7.5 vs 40.1 +/- 10.3, P = 0.005) and higher ESS scores
      than do simple snorers (8.8 +/- 5.1 vs 11.7 +/- 5.2, P = 0.03). Patients with a
      higher degree of sleepiness show worse performance in all dimensions of their
      general health status (P values 0.0005 to 0.01). Deep sleep (stage 3 + 4) is
      predictive of SF-36 role: physical (beta = 1.63, P = 0.04), bodily pain (beta =
      1.22, P = 0.01), vitality (beta = 1.05, P = 0.01), subscales scores (adjusted
      R(2) 0.005 to 0.1). CONCLUSION: SDB has considerable impact on a patient's global
      health status. SIGNIFICANCE: Daytime sleepiness, rather than apnea, is a major
      quality-of-life determinant. EBM RATING: B-2b.

PMID- 16949977
TI  - Local treatment of cricoid cartilage defects with rhBMP-2 induces growth plate
      like morphology of chondrogenesis.
AB  - OBJECTIVE: The ultrastructural characteristics of new bone and cartilage, induced
      at the site of cricoid cartilage defects treated with rhBMP-2 in rabbits, were
      investigated. STUDY DESIGN AND SETTING: A cricoid defect model was used. Fifteen
      rabbits were randomly and equally divided into 3 groups. Four rabbits from each
      group were treated with rhBMP-2, while one rabbit from each group was used as
      control. The rabbits were killed 1, 2, or 4 weeks after surgery. The healing
      pattern of the laryngeal wound was evaluated by light and transmission electron
      microscopy. RESULTS: Mineralized collagen type I matrix, osteoblasts, and
      osteoclast-like cells were present as early as 1 week after surgery. Well
      structured bone trabeculas and growth plate-like structures were present 4 weeks
      after surgery. CONCLUSION: Intramembranous and endochondral osteogenesis take
      place at the site of cricoid cartilage defects treated with rhBMP-2. Progenitor
      cells of cricoid perichondrium form a growth plate-like structure similar to the
      epiphyseal growth plate. SIGNIFICANCE: This study reveals the pattern of BMP-2
      induced repair of airway cartilage defects.

PMID- 16949978
TI  - Association of airway abnormalities and risk factors in 37 subglottic stenosis
      patients.
AB  - OBJECTIVES: The study objective is to characterize the airway abnormalities in a
      series of patients with subglottic stenosis (SGS) as they relate to etiology and
      risk factors. STUDY DESIGN AND SETTING: Retrospective review, academic medical
      center. Airway characteristics, patient demographics, and suspected risk factors
      were recorded from a database of SGS cases from 2001 to 2004. RESULTS: Thirty
      seven patients with SGS were identified; 22 of 37 had isolated SGS (59%).
      Intubation (10 of 37, 27%), high tracheotomy (4 of 37, 11%), and reflux (5 of 37,
      14%) comprised the bulk of cases; 13 of 37 (35%) were considered idiopathic. Of
      22 patients with isolated SGS, the majority 18 of 22 (P = 0.06) were women, 59%
      of which were idiopathic. Multiple-level cases (0 of 15) were idiopathic (P <
      0.001). Intubation was the most common cause of multiple site stenosis (6 of 15,
      40%). CONCLUSIONS: The majority of patients in this study had isolated lesions.
      These patients tend to have no apparent risk factors. Multi-level cases are
      associated with prolonged intubation and known injuries. The nature of
      "idiopathic" stenoses is discussed. SIGNIFICANCE: Clinical examination of SGS may
      be meaningful in understanding the etiology of the stenosis.

PMID- 16949979
TI  - Vibratory pattern of vocal folds under tension asymmetry.
AB  - OBJECTIVE: The aim of this study was to describe and analyze the vibratory
      pattern of vocal folds in an asymmetric situation. STUDY DESIGN AND SETTING:
      Cricothyroid muscle unilateral action was simulated on excised larynges on an
      experimental bench. Increasing airflow rates were applied to achieve vocal fold
      vibration. Electroglottography and an optoreflectometer device allowed analysis
      of separate and simultaneous vocal fold vibration. Spectra of the signals were
      obtained for each level of airflow variation. RESULTS: All experiments showed
      periodic vibration. A phase shift was noted between the two vocal folds.
      Subharmonics and biphonation were identified in all the experiments. CONCLUSION:
      Lax vocal folds were more susceptible to spectral changes with increasing
      airflow. SIGNIFICANCE: Knowledge of the consequences of mass, tension, and
      position asymmetries of the vocal folds is crucial for diagnosis making and
      defining therapeutic strategies in dysphonic patients. This study may contribute
      to the understanding of physiology of vocal fold interaction and its compensatory
      mechanisms.

PMID- 16949980
TI  - Reappraisal of metastatic lymph node topography in head and neck squamous cell
      carcinomas.
AB  - OBJECTIVE: To analyze the lymphatic distribution of metastatic carcinomatous
      cells in cervical lymph nodes in head and neck squamous cell carcinoma (HNSCC).
      STUDY DESIGN AND SETTING: We retrospectively reviewed 119 patients treated in our
      hospital for HNSCC (1999-2004). Topography of the neck dissection specimens was
      prospectively classified according to the classification of Robbins. The 4000
      lymph nodes were analyzed by optical microscopy using hematoxylin-eosin-safran
      (HES) staining. In cases of negative results in level II, cytokeratin (AE1/AE3)
      immunodetection was performed. RESULTS: Metastases were visualized using HES in
      6.4% of lymph nodes for oral cavity, and 4.7% of oropharyngeal, 4.4% of
      hypopharyngeal, and 1.3% of endolaryngeal cancers. The highest incidence of nodal
      metastasis was observed in level IIa (P < 0.01). In eight patients (6.7%) with
      lymph node metastases, level II was spared. In these patients, all 134 nodes
      histologically negative on HES were confirmed to be negative by IHC. CONCLUSIONS:
      Level IIa is the main level involved in regional metastases of HNSCC, regardless
      of the primary site of cancer. However, in eight (6.7%) patients, level II was
      spared, as confirmed by IHC. In these cases, level II did not represent the first
      step of drainage from the tumor. The sentinel lymph node technique in HNSCC is
      discussed in light of these results.

PMID- 16949981
TI  - Epidemiology of head and neck cancer in the United States.
AB  - BACKGROUND: Cancer rates of the head and neck are traditionally linked to public
      health issues. OBJECTIVE: To describe the epidemiology of head and neck cancer in
      the United States. DESIGN AND SETTING: National Cancer Institute's Surveillance
      Epidemiology and End Results (SEER) program. RESULTS: A total of 75,000 cases of
      head and neck cancer were diagnosed in 2001. Incidence is rising in thyroid (up
      52%), bone (43%) soft tissues (20%), salivary (20%), tongue (16%), tonsil (12%),
      and nose (12%). Incidence is falling in lip (down 58%), hypopharynx (35%),
      cervical esophagus (32%), oropharyngeal mucosa (26%), and larynx (26%). There
      were 30,000 deaths from head and neck cancer in 2001. Mortality has decreased to
      some degree at all sites except thyroid where it was stable. CONCLUSION: Many
      head and neck cancers have changing incidence and mortality rates contrary to
      expected changes given trends in public health issues. Further investigation of
      risk factors, diagnostic practices, and management strategies is warranted. EBM
      RATING: 2C.

PMID- 16949982
TI  - Modified superficial parotidectomy: preserving both the great auricular nerve and
      the parotid gland fascia.
AB  - OBJECTIVE: To reduce the incidence of sensory deficits and Frey's syndrome by
      modifying the traditional superficial parotidectomy. STUDY DESIGN: After raising
      the skin flap, the parotid gland fascia (PGF) was elevated to form a posterior
      pedicle fascial flap and then was replaced after the gland removal. The great
      auricular nerve (GAN) that runs within the PGF was not separated, so both the GAN
      and the PGF were preserved. Before this modification, the GAN and PGF were
      examined anatomically. The complication rates in the modified and control groups
      were compared. RESULTS: 1) The GAN, which runs within the thick and pycnotic PGF,
      trifurcates into postauricular, preauricular and lobule branches. The
      modification could be carried out practically based on the anatomy study. 2) Long
      term sensory deficit was encountered in 13.3% of the control group, but 0% in the
      modified one. Frey's syndrome was suffered by 66.7% and 16.7% cases in the
      control and modified group respectively. The incidence of other complications was
      not significantly different. CONCLUSION: Our modification is practical. It
      decreases the complications significantly. EBM RATING: B-3b.

PMID- 16949983
TI  - Removal of nonthyroidal neck masses with improved cosmetic outcomes in skin
      lifting surgery.
AB  - OBJECTIVE: To evaluate the cosmetic benefit of neck skin-lifting surgery for the
      removal of nonthyroidal neck masses. STUDY DESIGN AND SETTING: Fifty patients
      with neck masses were divided into the following 2 surgical groups that were
      matched in age, sex, and the size, location, and pathology of lesions: skin
      lifting (n = 25) and conventional (n = 25). The operation time, hospital stay,
      complications, and subjective satisfaction with the incision scar as assessed on
      a visual analogue scale (VAS) were compared between the 2 groups. RESULTS: All
      but 2 lesions (lymphomas) were benign and were removed completely, drained, or
      biopsied. The surgery time, hospital stay, and complication rates did not differ
      significantly between the groups. The mean satisfaction score of the patients was
      8.2 +/- 1.1 in the skin-lifting surgery group and 4.8 +/- 2.5 in the controls (P
      < 0.001). The incision scars were commonly hidden by natural hair or collars in
      the patients who received skin-lifting surgery. CONCLUSION: This surgical
      technique can be safely applied to most benign masses in the entire neck
      excluding the thyroid region, especially in patients who prefer neck scars to be
      invisible. EBM RATING: B-2b.

PMID- 16949984
TI  - Emerging technology: flexible CO2 laser WaveGuide.

PMID- 16949985
TI  - Amyloid infiltration of the salivary glands in the setting of primary systemic
      amyloidosis without multiple myeloma.

PMID- 16949986
TI  - Association of medullary and differentiated thyroid carcinomas.

PMID- 16949987
TI  - A surgical technique for macrostoma reduction after laryngectomy.

PMID- 16949988
TI  - Epidermoid of the retromastoidal region with cutaneous wound infection, fistula
      and epidural abscess.

PMID- 16949989
TI  - When should therapy be reinstituted for relapsed Wegener's granulomatosis?

PMID- 16949990
TI  - Candida laryngitis.

PMID- 16949991
TI  - Necrotizing parotitis: an unusual initial manifestation of Wegener's
      granulomatosis.

PMID- 16949992
TI  - Coblation lingual tonsillectomy.

PMID- 16949993
TI  - More on heterogeneity of clinical presentation of Eagle's syndrome.

PMID- 16949994
TI  - Duplicate publication.

PMID- 16949995
TI  - Chapter 1: HPV in the etiology of human cancer.
AB  - The causal role of human papillomavirus (HPV) in all cancers of the uterine
      cervix has been firmly established biologically and epidemiologically. Most
      cancers of the vagina and anus are likewise caused by HPV, as are a fraction of
      cancers of the vulva, penis, and oropharynx. HPV-16 and -18 account for about 70%
      of cancers of the cervix, vagina, and anus and for about 30-40% of cancers of the
      vulva, penis, and oropharynx. Other cancers causally linked to HPV are non
      melanoma skin cancer and cancer of the conjunctiva. Although HPV is a necessary
      cause of cervical cancer, it is not a sufficient cause. Thus, other cofactors are
      necessary for progression from cervical HPV infection to cancer. Long-term use of
      hormonal contraceptives, high parity, tobacco smoking, and co-infection with HIV
      have been identified as established cofactors; co-infection with Chlamydia
      trachomatis (CT) and herpes simplex virus type-2 (HSV-2), immunosuppression, and
      certain dietary deficiencies are other probable cofactors. Genetic and
      immunological host factors and viral factors other than type, such as variants of
      type, viral load and viral integration, are likely to be important but have not
      been clearly identified.

PMID- 16949996
TI  - Chapter 12: Prophylactic HPV vaccines: underlying mechanisms.
AB  - Human papillomavirus virus-like particles (HPV VLP) can be generated by the
      synthesis and self-assembly in vitro of the major virus capsid protein L1. HPV L1
      VLPs are morphologically and antigenically almost identical to native virions,
      and this technology has been exploited to produce HPV L1 VLP subunit vaccines.
      The vaccines elicit high titres of anti-L1 VLP antibodies that persist at levels
      10 times that of natural infections for at least 48 months. At present the
      assumption is that the protection achieved by these vaccines against incident HPV
      infection and HPV-associated ano-genital pathology is mediated via serum
      neutralising Immunoglobulin G (IgG). However, since there have been very few
      vaccine failures thus far, immune correlates of protection have not been
      established. The available evidence is that the immunodominant neutralising
      antibodies generated by L1 VLPs are type-specific and are not cross-neutralising,
      although highly homologous HPV pairs share minor cross-neutralisation epitopes.
      Important issues remaining to be addressed include the duration of protection and
      genotype replacement.

PMID- 16949997
TI  - Chapter 2: The burden of HPV-related cancers.
AB  - On the basis of current evidence regarding human papillomavirus (HPV) and cancer,
      this chapter provides estimates of the global burden of HPV-related cancers, and
      the proportion that are actually "caused" by infection with HPV types, and
      therefore potentially preventable. We also present trends in incidence and
      mortality of these cancers in the past, and consider their likely future
      evolution.

PMID- 16949998
TI  - Chapter 13: Current findings from prophylactic HPV vaccine trials.
AB  - Early data from randomized controlled trials consistently show that prophylactic
      human papillomavirus virus-like particle (HPV VLP) vaccines are effective in
      preventing infection and lesions caused by the targeted HPV type(s). Two
      vaccines, a bivalent HPV-16/18 VLP vaccine and a quadrivalent HPV-6/11/16/18 VLP
      vaccine, are currently undergoing evaluation in phase III trials with
      anticipation of receiving regulatory approval for use in immunization programs
      worldwide. Both vaccines have the potential to substantially reduce HPV-related
      morbidity and mortality. This review focuses on published data from clinical
      trials of these two vaccines.

PMID- 16949999
TI  - Chapter 14: HPV vaccine introduction in industrialized countries.
AB  - Introduction of a vaccine requires the achievement of three initial milestones.
      These are licensure by a national control authority that determines the vaccine
      is safe and effective, development of recommendations for use by expert advisory
      bodies on immunization, and obtaining funding for vaccination. Once these
      milestones have been achieved, a successful vaccination program requires that a
      number of interlinked programmatic components be brought together in a
      coordinated fashion. These include vaccine purchase and supply, vaccination
      service delivery, high coverage rates, surveillance of the vaccination program,
      immunization finance policies and practices, and political will. Human
      papillomavirus (HPV) vaccination provides unique challenges in all of these areas
      because of the many gaps in our knowledge.

PMID- 16950000
TI  - Chapter 15: HPV vaccine use in the developing world.
AB  - Human papillomavirus (HPV)-related morbidity and mortality from cervical cancer
      primarily occurs in the developing world, where, unfortunately, access to
      vaccines in general, and expensive newer vaccines in particular, is often more
      limited than in the industrialized world. In addition, secondary prevention
      methods such as HPV screening, Pap testing, or visual inspection are uncommon in
      the developing world. The HPV vaccine will be first introduced into the
      industrialized countries and it will then, over the course of time, become used
      in the developing countries. HPV vaccine should be introduced in the framework of
      comprehensive cervical cancer control, and offers an opportunity to bring
      together a wide range of constituents who have not to date worked closely on
      vaccination. Ultimately, the decision of whether and when a vaccine will be
      introduced will depend on individual countries. To prepare for decisions on HPV
      vaccine use, the sexual and reproductive health (SRH; including adolescent
      health), immunization, and cancer control communities need to work together to
      analyze the appropriate data and build international and national consensus. The
      timeframe for other newer vaccines, such as hepatitis B and Hib, has been
      measured in decades, and the challenge to the public sector is to greatly shorten
      the time needed to make HPV vaccines available and affordable for the developing
      world, where their impact will be greatest.

PMID- 16950001
TI  - Chapter 16: HPV vaccines in immunocompromised women and men.
AB  - HIV-positive as well as other immunocompromised women and men have increased risk
      of human papillomavirus (HPV)-associated anogenital and oral cancers. The
      effectiveness of a HPV vaccine to reduce the incidence of these tumors in
      immunocompromised individuals may depend on several factors, including the
      effects of immunocompromise on the response to vaccination, the extent of prior
      infection with the HPV types included in the vaccine, whether immunocompromised
      women and men have tumors that contain types of HPV not in the vaccines more
      often than the general population, and whether or not immunization occurs before
      immunocompromise is severe. Clinical studies are needed to determine HPV vaccine
      safety and effectiveness in different populations of immunocompromised women and
      men.

PMID- 16950002
TI  - Chapter 17: Second generation HPV vaccines to prevent cervical cancer.
AB  - Prophylactic human papillomavirus (HPV) vaccines based on intramuscular injection
      of non-infectious L1 virus-like particles (VLPs) are undergoing intense clinical
      evaluation. As documented in preceding chapters of this monograph, clinical
      trials of these vaccines have demonstrated their safety and high efficacy at
      preventing type-specific persistent cervical HPV infection and the development of
      type-specific cervical intraepithelial neoplasia (CIN) cervical neoplasia. There
      is widespread optimism that VLP vaccines will become commercially available
      within the next few years. The prospects for development of alternative HPV
      vaccines must be considered in light of the likelihood that a safe and effective
      prophylactic HPV vaccine will soon be available. Three questions need to be
      addressed: (1) Is there sufficient need for a second generation vaccine? (2) Are
      there sufficiently attractive candidates for clinical trials? (3) Is there a
      realistic development/commercialization path?

PMID- 16950003
TI  - Chapter 18: Public health policy for cervical cancer prevention: the role of
      decision science, economic evaluation, and mathematical modeling.
AB  - Several factors are changing the landscape of cervical cancer control, including
      a better understanding of the natural history of human papillomavirus (HPV),
      reliable assays for detecting high-risk HPV infections, and a soon to be
      available HPV-16/18 vaccine. There are important differences in the relevant
      policy questions for different settings. By synthesizing and integrating the best
      available data, the use of modeling in a decision analytic framework can identify
      those factors most likely to influence outcomes, can guide the design of future
      clinical studies and operational research, can provide insight into the cost
      effectiveness of different strategies, and can assist in early decision-making
      when considered with criteria such as equity, public preferences, and political
      and cultural constraints.

PMID- 16950004
TI  - Chapter 19: Cost-effectiveness of cervical cancer screening.
AB  - In the last two decades, computer-based models of cervical cancer screening have
      been used to evaluate the cost-effectiveness of different secondary prevention
      policies. Analyses in countries with existing screening programs have focused on
      identifying the optimal screening interval, ages for starting and stopping
      screening, and consideration of enhancements to conventional cytology, such as
      human papillomavirus (HPV)-DNA testing as a triage for equivocal results or as a
      primary screening test for women over the age of 30. Analyses in resource-poor
      settings with infrequent or no screening have focused on strategies that enhance
      the linkage between screening and treatment, consider noncytologic alternatives
      such as HPV-DNA testing, and target women between the ages of 35 and 45 for
      screening one, two, or three times per lifetime. Despite differences in methods
      and assumptions, this paper identifies the qualitative themes that are consistent
      among studies, and highlights important methodological challenges and high
      priority areas for further work.

PMID- 16950005
TI  - Chapter 21: Modelling the impact of HPV vaccines on cervical cancer and screening
      programmes.
AB  - The impact of human papillomavirus (HPV)-16/18 vaccination on the incidence of
      infection and disease can be explored in a range of different models. Here we
      explore the epidemiological and economic impact of vaccination where screening is
      absent and where it is well established. The importance for epidemiology of
      assumptions about naturally-acquired immunity and heterogeneity in risk
      behaviours are highlighted, as are the importance for health economic outcomes of
      vaccine costs and the ability to modify screening strategies. To date, model
      results are consistent in predicting a useful role for vaccine, but further
      epidemiological data are required to help test the validity of models.

PMID- 16950006
TI  - Chapter 22: Assuring the quality, safety and efficacy of HPV vaccines: the
      scientific basis of regulatory expectations pre- and post-licensure.
AB  - The potential of human papillomavirus (HPV) vaccines will only be realized if the
      vaccine candidates under development prove to be safe and effective and can be
      consistently produced to define quality standards. Whilst the responsibility for
      delivering a safe and effective product rests with the vaccine producer, a
      vaccine requires a license to allow it to be placed on the market. Licensure is
      based on an evaluation of the safety and efficacy profile of a vaccine candidate
      by national regulatory authorities, ideally on the basis of internationally
      agreed, science-based specifications and procedures. For vaccines, these
      international specifications are developed by the World Health Organization
      (WHO). The scientific basis for the regulatory evaluation of the safety and
      efficacy of HPV vaccines is described in this paper. Once a vaccine is licensed,
      a second set of criteria are evaluated by a different group of experts to provide
      advice to national health policy decision makers as to whether the vaccine should
      be introduced into national immunization programmes. Factors, such as evidence of
      high disease burden and high cost-effectiveness are taken into account in this
      second decision-making process.

PMID- 16950007
TI  - Chapter 23: International Standard reagents for harmonization of HPV serology and
      DNA assays--an update.
AB  - International reference materials such as International Standard reagents
      facilitate quality assurance of essential biopharmaceutical products and related
      in vitro diagnostic tests. Standardization of antibody and DNA measurements and
      harmonization of laboratory procedures are key to the success of cancer
      prevention strategies through screening methods as well as for development and
      implementation of vaccination against the human papillomavirus (HPV). The WHO
      supported the preparation and initial analysis of a panel of candidate
      serological and DNA reference reagents aimed at facilitating inter-laboratory
      comparisons and detection of HPV worldwide. Two international collaborative
      studies assessed the performance of various HPV antibody and HPV-DNA detection
      assays and examined the feasibility of generating HPV antibody and DNA standard
      reagents. These studies showed that improvement in performance and comparability
      of assays is urgently needed and that the use of the same International Standard
      reference reagent could significantly improve performance and comparability. It
      is hoped that the establishment of International Units and International
      Standards for HPV antibody and DNA analysis will be pursued with high priority.

PMID- 16950008
TI  - Chapter 24: Psychosocial aspects of vaccine acceptability.
AB  - In this chapter we identify psychosocial issues that have been raised with
      respect to human papillomavirus (HPV) vaccination and review the research
      literature on HPV vaccine acceptability. Many women and physicians have
      relatively poor knowledge about HPV, but despite this, most healthcare providers
      are willing to recommend HPV vaccination and parents are interested in having
      their children vaccinated. Concerns about post-vaccination sexual behavior change
      do not appear to be justified, but can certainly be addressed through
      anticipatory guidance. Most research studies have come out of the United States
      and other English-speaking industrialized countries. More psychosocial research
      regarding HPV vaccination is therefore needed from developing countries.

PMID- 16950009
TI  - Chapter 25: Education, training, and communication for HPV vaccines.
AB  - As human papillomavirus (HPV) vaccines come to market, they will face education
      and training challenges similar to those of other new vaccines, along with HPV
      specific issues. Recent studies document stark knowledge gaps about HPV at all
      levels--among policy makers, healthcare providers, parents, and teens--in both
      the industrialized and developing worlds. Pharmaceutical companies, public health
      advocates, medical trainers, and health educators need to understand their
      diverse audiences and respond appropriately to the needs of each. They also must
      use research-based communication strategies and materials to most effectively,
      and accurately, convey the need for an HPV vaccine and to manage expectations
      about how the vaccine can, and cannot, protect women and men.

PMID- 16950010
TI  - Chapter 26: Innovative financing mechanisms to accelerate the introduction of HPV
      vaccines in developing countries.
AB  - The costs of developing and producing new-generation vaccines have increased
      compared to many of the older, "traditional" vaccines because of new technologies
      and regulatory requirements. While the public sector often supports basic
      research costs, private manufacturers are usually responsible for the investments
      in product development and production scale-up. When considering investments,
      firms evaluate the probability of a market. Unfortunately, the developing country
      vaccine market is small (in revenue terms) and often unpredictable, particularly
      given inaccurate forecasting in the past. Low-income developing countries expect
      low prices. Demand (actual decisions to pay for and introduce the vaccine) is
      almost always lower than need (estimates of requirements to achieve optimal
      public health outcomes), a distinction that may be even more significant for HPV
      vaccines given the number of new vaccines against priority diseases that will
      become available over the coming 5 years. One new mechanism under consideration
      to address some of these challenges is Advanced Market Commitments (AMCs). By
      providing an assured price subsidy for developing country purchase of a future
      vaccine meeting predefined standards, an AMC would provide industry with greater
      assurances of earning a reasonable return on their investment to serve the
      poorest developing countries. The AMC mechanism could provide critical motivation
      for increased industry (private) investment that would otherwise not occur. HPV
      vaccines are one of six vaccines being considered for a possible AMC pilot.

PMID- 16950011
TI  - Chapter 27: Research needs following initial licensure of virus-like particle HPV
      vaccines.
AB  - Human papillomavirus virus-like particle (HPV VLP) HPV vaccines currently
      evaluated for licensing are likely to be available soon. Licensure will be based
      on evidence that the vaccine is well tolerated and provides near complete type
      specific protection against HPV infections and their resulting lesions in the
      first few years after vaccination. Several important questions will remain to be
      answered after licensure to guide vaccine implementation and to permit the
      rational evaluation of vaccination in cancer prevention programs. These include
      the long-term safety and efficacy of vaccination, the optimal ages for
      vaccination, efficacy against HPV types not included in the vaccine and against
      existing infections, and efficacy in males. Modulators of vaccine efficacy (e.g.,
      HIV infection) and immune mechanisms of long-term protection also remain to be
      defined. The real-world effectiveness of vaccination programs will need to be
      assessed. Issues related to the implementation of a vaccine that targets pre
      adolescents and early adolescents and to the acceptability of a cancer vaccine
      targeted against a sexually transmitted infection will need to be understood
      before vaccination programs can be successful. It is hoped that continued
      improvements to the current HPV vaccines will lead to the introduction in future
      years of second generation vaccines that simplify delivery and/or expand its
      coverage. Finally, the natural history of HPV types not covered in the candidate
      vaccines will need to be carefully studied following vaccination. Public health
      authorities in various countries will play a pivotal role in determining if these
      questions are answered in a timely manner.

PMID- 16950012
TI  - Chapter 28: Studies to assess the long-term efficacy and effectiveness of HPV
      vaccination in developed and developing countries.
AB  - We review studies of the implementation of human papillomavirus (HPV) vaccination
      programmes in developed and developing countries. The review spans the period
      from establishment of long-term vaccine efficacy follow-up studies, operational
      research on issues of vaccine preparedness, and relevant predictive modelling
      studies during the pre-licensure phase to plans of phase IV effectiveness trials,
      forms of epidemiological surveillance, and further operational research in the
      post-licensure phase. Much of the research is already ongoing. Depending on the
      results of the planned immuno bridging studies among HIV-negative and HIV
      positive women, further phase III and/or phase IV trials may be warranted.

PMID- 16950013
TI  - Chapter 29: Knowledge gaps and priorities for research on prevention of HPV
      infection and cervical cancer.
AB  - The recognition that human papillomavirus (HPV) infection is the necessary cause
      of cervical cancer brought new prevention paradigms in screening and HPV
      immunization. We now face many questions about how to implement an ambitious
      evidence-based agenda for cervical cancer prevention. Much is known about the
      epidemiology and natural history of HPV infection but several key variables
      remain to be elucidated. Research on HPV transmission requires new study designs
      to provide useful insights into preventive strategies. HPV testing has carved a
      niche in clinical practice but to consolidate its role in screening still
      requires evidence of long-term benefit. The rapidly evolving field of HPV
      diagnostics has contributed useful information concerning the value of HPV
      typing. Other screening methods hold promise in specific settings. The decade
      long process that brought HPV vaccines to the doorstep of public health
      application is over. Many questions remain concerning long-term efficacy,
      correlates of protection, age of vaccination, and delivery. As vaccination makes
      inroads as a cancer control strategy, screening practices must be reformulated to
      maximize the synergy between primary and secondary prevention. Research on how to
      achieve an efficient combination of these modalities is yet to begin, but
      mathematical models have provided a useful road map for field-testing of
      promising algorithms. Daunting questions loom large concerning delivery of
      vaccines to those populations that need it the most. The field of HPV and
      cervical cancer prevention has never been so multi-disciplinary. A new era has
      begun and the challenges are many.

PMID- 16950014
TI  - Chapter 30: HPV vaccines and screening in the prevention of cervical cancer;
      conclusions from a 2006 workshop of international experts.
AB  - The finding that cervical cancer only occurs in women infected with specific,
      "high-risk" types of the human papillomavirus (HPV) has led to the development of
      novel, non-cytology-based cervical cancer prevention strategies. We now have
      sensitive molecular methods for detecting HPV that dramatically improve our
      ability to detect high-grade cervical cancer precursor lesions. Perhaps more
      importantly, prophylactic HPV vaccines have been developed that are protective
      against cervical cancer precursors caused by HPV 16 and 18. In the Spring of
      2006, over 100 experts in HPV, cervical cancer screening, and vaccination worked
      together to define how best to incorporate HPV DNA testing and the HPV vaccines
      into cervical cancer prevention efforts. In this summary, we summarize the
      opinions of this expert group on how these advances can be introduced to provide
      the maximum benefit to women and to reduce the global burden of cervical cancer.

PMID- 16950015
TI  - Chapter 3: HPV type-distribution in women with and without cervical neoplastic
      diseases.
AB  - Geographical widespread data on human papillomavirus (HPV) type-distribution are
      essential for estimating the impact of HPV-16/18 vaccines on cervical cancer and
      cervical screening programmes. Epidemiological studies employing a variety of HPV
      typing protocols have been collated in meta-analyses. HPV-16/18 is estimated to
      account for 70% of all cervical cancers worldwide, although the estimated HPV
      16/18 fraction is slightly higher in more developed (72-77%) than in less
      developed (65-72%) regions. About 41-67% of high-grade squamous intraepithelial
      lesion (HSIL), 16-32% of low-grade squamous intraepithelial lesion (LSIL) and 6
      27% of atypical squamous cells of undetermined significance (ASCUS) are also
      estimated to be HPV-16/18-positive, thus highlighting the increasing relative
      frequency of HPV-16/18 with increasing lesion severity. After HPV-16/18, the six
      most common HPV types are the same in all world regions, namely 31, 33, 35, 45,
      52 and 58; these account for an additional 20% of cervical cancers worldwide.

PMID- 16950016
TI  - Chapter 4: Burden and management of non-cancerous HPV-related conditions: HPV
      6/11 disease.
AB  - Human Papillomavirus (HPV)-6 and -11 are the causative agents of ano-genital
      warts (GWs) and recurrent respiratory papillomatosis (RRP). They are low-risk HPV
      types that are uncommonly found in malignant lesions. GWs are an extremely
      prevalent sexually transmitted disease, whereas RRP is a rare disease that can be
      life threatening and requires multiple surgical procedures. GWs and RRP cause
      substantial healthcare costs. A quadrivalent HPV-6/11/16/18 vaccine (Merck/SPMSD)
      has shown essentially 100% protection against GWs in women in early studies. Cost
      effectiveness analyses are needed to assess the benefits of the HPV-6/11 virus
      like particle (VLP) components of the quadrivalent vaccine in population-based
      vaccination programmes.

PMID- 16950017
TI  - Chapter 5: Updating the natural history of HPV and anogenital cancer.
AB  - The major steps in cervical carcinogenesis include infection of the metaplastic
      epithelium of the cervical transformation zone with one or more of the 12-18
      carcinogenic types of human papillomavirus (HPV) infection, viral persistence,
      clonal progression of the persistently-infected epithelium to cervical precancer,
      and invasion. Although these fundamental steps are established, several new
      epidemiologic studies have shed light on the factors that influence each of these
      transitions. The importance of the transformation zone in cervical cancer has
      been extended to other HPV-induced cancers such as anal or tonsillar cancers.
      Natural history studies show that HPV with normal cervical cytology and cervical
      intraepithelial neoplasia (CIN) grade 1 behave similarly, with the majority of
      both showing regression. Although these studies have demonstrated the importance
      of HPV persistence in the development of precancer CIN-3, the timing from
      infection to evidence of CIN-3 varies from 1 to 10 years. Whether equivalent
      lesions diagnosed later differ in their natural history remains unknown. Several
      factors have been implicated in enhancing persistence and/or progression.
      However, none are consistently associated with both except age: young women are
      less likely to show persistence and older women with persistence are more likely
      to be at risk of invasive cancer. Recent studies have also underscored the
      importance of the host immune response in clearance of established infections.
      Finally, data on non-cervical HPV infections, such as penile infections are
      limited to date compared to cervical infections. Several ongoing cohort studies
      should give us further insight into male infections in the near future.

PMID- 16950018
TI  - Chapter 6: Epidemiology and transmission dynamics of genital HPV infection.
AB  - This chapter provides an overview of the epidemiology of human papillomavirus
      (HPV) infection, with a focus on the dynamics of sexual transmission. We explore
      concepts related to the spread of sexually transmitted infections, including
      population prevalence, duration of infectivity, patterns of sexual contacts, and
      transmissibility, including modifiers of susceptibility and infectivity. HPV
      prevalence and incidence are high in most studies, particularly amongst young
      women. There is strong evidence that transmission occurs primarily via sexual
      activity, most commonly vaginal and anal intercourse. Although the duration of
      infectivity may be short, current evidence suggests that HPV is highly
      transmissible. The implications of transmission dynamics for the success of
      future HPV vaccines are discussed.

PMID- 16950019
TI  - Chapter 7: Achievements and limitations of cervical cytology screening.
AB  - This chapter reviews the contribution of cervical cytology, what makes it
      successful, the management of screen positives and how technological advances may
      affect its use in the future. Cervical screening has saved hundreds of thousands
      of lives but has not been available to women in the poorest countries. In
      countries where wide coverage has been achieved and quality assurance is in
      place, incidence and death rates have fallen by over 50% even though cervical
      cytology is logistically complex. The management of high-grade cervical
      intraepithelial neoplasia (CIN) is very effective, but low-grade cytological
      abnormalities require care to avoid over-treatment. The increasing rate of human
      papillomavirus (HPV) testing and the prospect of prophylactic vaccination will
      change the way cervical cytology is used, possibly giving way to HPV testing as
      the primary test in secondary prevention.

PMID- 16950020
TI  - Chapter 8: Screening for cervical cancer in developing countries.
AB  - Organised and quality assured cytology-based screening programmes have
      substantially reduced cervical cancer incidence in many developed countries.
      However, there are considerable barriers to setting up cytology-based screening
      programs, particularly in developing countries. This has stimulated the search
      for novel and alternative approaches to cytology for cervical cancer prevention.
      These approaches generally perform as well as cytology, and sometimes better,
      although many of them have a lower specificity, resulting in higher false
      positive rates. The possibility of linking screening to treatment in a one- or
      two-visit strategy appears to be safe, feasible and effective. Barriers to
      establishing screening programs and the pitfalls encountered differ from one
      country to the next. Country-specific solutions need to be found, while being
      cognizant of the criteria that have enabled successful screening programmes.

PMID- 16950021
TI  - Chapter 9: Clinical applications of HPV testing: a summary of meta-analyses.
AB  - BACKGROUND: More than ever, clinicians need regularly updated reviews given the
      continuously increasing amount of new information regarding innovative cervical
      cancer prevention methods. MATERIAL AND METHODS: A summary is given from recently
      published meta-analyses on three possible clinical applications of human
      papillomavirus (HPV)-DNA testing: triage of women with equivocal or low-grade
      cytological abnormalities; prediction of the therapeutic outcome after treatment
      of cervical intraepithelial neoplasia (CIN) lesions, and last not but not least,
      primary screening for cervical cancer and pre-cancer. RESULTS: Consistent
      evidence is available indicating that HPV-triage with the Hybrid Capture-2 assay
      (HC2) is more accurate (significantly higher sensitivity, similar specificity)
      than repeat cytology to triage women with equivocal Pap smear results. When
      triaging women with low-grade squamous intraepithelial lesions (LSIL), a reflex
      HC2 test does not show a significantly higher sensitivity, but a significantly
      lower specificity compared to a repeat Pap smear. After treatment of cervical
      lesions, HPV testing easily detects (with higher sensitivity and not lower
      specificity) residual or recurrent CIN than follow-up cytology. Primary screening
      with HC2 generally detects 23% (95% confidence interval, CI: 13-23%) more CIN-2,
      CIN-3, or cancer compared to cytology at cut-off atypical squamous cells of
      undetermined significance (ASCUS) or LSIL, but is 6% (95% CI: 4-8%) less
      specific. By combined HPV and cytology screening, a further 4% (95% CI: 3-5%)
      more CIN-3 lesions can be identified but at the expense of a 7% (95% CI: 5-9%)
      loss in specificity, in comparison with isolated HC2 screening. CONCLUSIONS:
      Sufficient evidence exists to recommend HPV testing in triage of women with
      atypical cytology and in surveillance after treatment of CIN lesions. In the
      United States, recently reviewed knowledge has resulted in the approval of
      combined cytology and HC2 primary screening in women older than 30 years.
      However, in Europe, cytology-based screening still remains the standard screening
      method. The European screening policy will be reviewed based on the longitudinal
      results of randomised population trials which are currently underway.

PMID- 16950022
TI  - Chapter 10: New dimensions in cervical cancer screening.
AB  - Human papillomavirus (HPV) testing has clearly demonstrated a higher sensitivity
      but somewhat lower specificity than cytology. However, there are still issues
      regarding how best to use it in primary screening. In countries where cytology is
      of good quality, the most interesting possibility for primary screening is to use
      HPV testing as the sole screening modality with cytology reserved for triage of
      HPV-positive women. In countries with a less established infrastructure, however,
      use of HPV alone would also be attractive, although rapid, simple tests followed
      by immediate treatment are needed to minimize the number of visits and make best
      use of limited resources. Several approaches to deal with the lower specificity
      of HPV testing are also examined. These include HPV typing with a different
      management strategy for HPV-16 and -18/45, use of viral load to exclude
      infections unlikely to be associated with > or =CIN-2, and markers of
      proliferative lesions such as p16 and mRNA or cell-cycle markers such as cdc6 or
      the mcm5 proteins. Micro-array studies offer the prospect of discovering new,
      better DNA- or RNA-based diagnostics. The fact that HPV is a sexually transmitted
      infection may lead to anxiety and concerns about sexual relationships and these
      issues are also discussed. Ongoing HPV studies are identified and briefly
      reviewed.

PMID- 16950023
TI  - Chapter 11: HPV vaccines: commercial research & development.
AB  - We are now in the fortunate position of having two highly promising human
      papillomavirus (HPV) vaccines in the pipeline. Amidst the excitement of
      anticipating what these vaccines may be able to offer, it is worth pausing to
      look back at how the vaccine development story unfolded from an industrial
      perspective, since without the massive commitment shown by manufacturers over the
      last decade, without any guarantee of success, there would be no such prospect.
      This chapter focuses on the two HPV prophylactic vaccines, produced independently
      by Merck & Co., Inc. and GlaxoSmithKline (GSK), that are in advanced clinical
      development, and it aims to provide an insight into the key considerations for
      initiating the programmes in a commercial context as well as some of the research
      and development hurdles that needed to be surmounted to bring them to the point
      where efficacy has been demonstrated and the licensing process is well underway.

PMID- 16950024
TI  - Perspectives of contemporary papillomavirus research.

PMID- 16950025
TI  - Preface. The field of cervical cancer prevention.

PMID- 16950026
TI  - Navigation-assisted less invasive total knee arthroplasty compared with
      conventional total knee arthroplasty: a randomized prospective trial.
AB  - The purpose of this study was to evaluate the hypothesis that a less invasive
      (LIS) surgical technique using a navigation system would promote rapid recovery
      and improve alignment compared with conventional technique in total knee
      arthroplasty (TKA). This study compared 49 navigation-assisted LIS TKAs with 53
      conventionally performed TKAs using a medial parapatellar arthrotomy with
      patellar eversion. Navigation-assisted LIS TKA used a shorter skin incision, a
      midvastus approach without patella eversion, and a navigation system. Navigation
      assisted LIS TKA had better pain scores, shorter times to achieve 90 degrees
      flexion and straight leg raise, and a smaller extension lag during the very early
      postoperative period. However, there were no differences between the groups 2
      weeks postoperatively. There were no differences in mean prosthetic alignment
      between the 2 groups, but the navigation-assisted LIS group had fewer "outliers"
      than the conventionally performed TKA group.

PMID- 16950027
TI  - Durability of implant fixation after less-invasive total hip arthroplasty.
AB  - Less-invasive techniques for total hip arthroplasty (THA) have sparked an
      increased interest among orthopedic surgeons and patients. There has been concern
      regarding decreased surgical exposure and compromise in prosthesis durability. We
      present the first long-term outcome of THA performed via the mini-incision
      posterior approach to show the durability of implant fixation. We compare the
      clinical and radiographic findings with previously published findings of authors
      using the same femoral implant and standard surgical techniques over a similar
      follow-up period. Ninety implants were followed for 10 to 13 years. Clinical
      evaluation revealed a Harris Hip Score of 92.3. Radiographic evaluation revealed
      proximal bone atrophy in 57% and lucent lines in 14% of femurs and 11% of cups.
      Osteolysis was noted in 10% and was associated with polyethylene wear. There were
      no cases of aseptic stem loosening. Eight polyethylene inserts were revised for
      wear. These 10-year minimum follow-up findings are consistently comparable with
      previously published studies using the same implant and larger surgical
      approaches followed for a similar period. Mini-incision THA technique did not
      compromise the long-term clinical and radiographic findings when compared with
      conventional techniques.

PMID- 16950028
TI  - The temporal progression of pelvic osteolysis after uncemented total hip
      arthroplasty.
AB  - This study examined the natural progression of pelvic osteolysis post uncemented
      total hip arthroplasty. Serial radiographs from 145 total hip arthroplasties with
      minimum 10-year follow-up were examined. Thirty-two lesions were identified in 25
      hips and their 2-dimensional radiographic size over time was measured via
      computer. Lesion growth rate averaged 42.7 +/- 49.0 mm2/y. Linear models were
      generally a good fit for lesion growth as evidenced by a high mean r2 value (0.77
      +/- 0.18); lesions progressed steadily during the first 10 postoperative years.
      Although lesions were first radiographically evident 5.7 years postarthroplasty,
      the x-intercept of the linear model, approximating the mean time when the lesions
      first began to develop, averaged 1.3 years. Because this study expands our
      understanding of when and how peri-acetabular lesions develop, it can be useful
      to clinicians in determining how often to see patients postoperatively.

PMID- 16950029
TI  - Sciatic nerve palsy after primary total hip arthroplasty: a new perspective.
AB  - More than half of sciatic nerve palsies after primary total hip arthroplasties
      are unexplained. In 2 such cases, magnetic resonance imaging localized
      compressive injury between the ischial tuberosity and femoral insertion of the
      gluteus maximus. After these cases, we hypothesized that during limb positioning,
      the sciatic nerve is compressed by the gluteus maximus tendon. We present the
      magnetic resonance imaging findings from these 2 cases and compare the number of
      sciatic nerve palsies in patients with release of the gluteus maximus tendon to
      patients without release during primary total hip arthroplasty. There were no
      cases of sciatic nerve palsy when the gluteus maximus was released, compared with
      3 cases in the control group.

PMID- 16950030
TI  - Ten-year survival and clinical results of constrained components in primary total
      knee arthroplasty.
AB  - The use of constrained prostheses in primary total knee arthroplasty (TKA) is
      unusual. This is a study of the indications, clinical results, and 10-year
      survival of these components. Fifty-four knees (44 patients) were prospectively
      followed, and 42 knees (34 patients) had 5 to 16 years (mean, 9 years) of follow
      up. The indications for the components were valgus deformity with incompetent
      medial collateral ligament in 27 knees, severe flexion contracture with inability
      to balance the knee in 12, and others in 3. Knees were evaluated by the Hospital
      for Special Surgery and Knee Society score systems. Statistical analysis included
      paired Student t test and survivorship analysis. Of the entire cohort of 54
      knees, there were only 2 failures: a tibial loosening revised at 3 years and a
      femoral loosening (no stem) revised at 1 year. Of the 42 knees with minimum 5
      year follow-up, 12 knees were rated as excellent, 24 good, 3 as fair, and 3 as
      poor. There was a significant improvement in postoperative knee score, but not in
      the function score. The mean flexion contracture preoperatively was 17 degrees;
      postoperatively, 1.7 degrees; and mean flexion preoperatively, 93 degrees;
      postoperatively, 97 degrees. The 10-year survival with failure, defined as
      component revision for loosening, was 96% (confidence interval, 90.6%-100%). In
      difficult primary TKAs, there were 86% good or excellent results and a 10-year
      survival of 96% despite the increased constraint. The constrained condylar TKA
      remains indicated for knees with severe valgus deformity, incompetent medial
      collateral ligament, or severe flexion contracture in which the knee cannot be
      properly balanced.

PMID- 16950031
TI  - The effect of posterior tibial slope on range of motion after total knee
      arthroplasty.
AB  - Posterior slope has been theorized as advantageous to range of motion (ROM) after
      total knee arthroplasty. This study was undertaken to assess the accuracy of a 0
      degrees and a 5 degrees posterior sloped intramedullary (IM) cutting guide and
      the effect of the posterior tibial slope on postoperative ROM. Thirty-one
      consecutive patients underwent total knee arthroplasty using a cutting block and
      intramedullary cutting guide designed to impart a 0 degrees posterior tibial
      slope (group 1). A 5 degrees tibia cutting block was used in 30 subsequent
      patients (group 2). The posterior slope measurement represented the angle between
      a line drawn parallel to the articular surface and a line drawn perpendicular to
      the long axis of the tibia on a lateral radiograph. Mean postoperative tibial
      slope measured 1.8 degrees for group 1 and 5.5 degrees for group 2. There was no
      significant difference between groups for postoperative flexion or improvement of
      Hospital for Special Surgery score. The tibial cutting guides accurately achieved
      the intended posterior slope, but increasing posterior slope did not result in a
      significant increase in ROM or Hospital for Special Surgery functional score.

PMID- 16950032
TI  - Prospective analysis of a novel long-acting oral opioid analgesic regimen for
      pain control after total hip and knee arthroplasty.
AB  - Parenteral opioid use after total knee (TKA) and hip (THA) arthroplasty often
      results in substantial functional interference and side effects. This prospective
      study compared use of traditional intravenous patient-controlled analgesia (IV
      PCA) with a novel oral regimen after TKA and THA. Sixty-two patients received IV
      PCA and 62 received scheduled long-acting and, as needed, short-acting oral
      opioids postoperatively. Surveys and chart audits documented functional
      interference, pain scores, opioid-related side effects, and opioid consumption.
      Patients who received the oral regimen had significantly less opioid consumption
      (P < .05) and experienced less functional interference (P < .05) than the IV PCA
      group. Both groups had similar pain scores and incidence of opioid side effects.
      This study demonstrates some significant advantages of an oral analgesic regimen
      compared with IV PCA after TKA and THA.

PMID- 16950033
TI  - A third-generation, posterior-stabilized knee prosthesis: early results after
      follow-up of 2 to 6 years.
AB  - Two hundred seventy-nine primary total knee arthroplasties were performed with a
      modular, cemented, third-generation, posterior-stabilized prosthesis. At mean
      follow-up of 48 months (range, 24-72 months), the outcomes of 238 knees (85%)
      were evaluated with the Knee Society's Knee and Functional Scoring Systems and
      Roentgenographic Scoring System. The mean preoperative Knee Society Knee Score
      was 48 points compared with 96 points at latest follow-up. There were no cases of
      patellar clunk, symptomatic patellar maltracking, or posterior dislocation. There
      was no radiographic evidence of loosening or osteolysis, and no revisions were
      performed or recommended for loosening, osteolysis, instability, or polyethylene
      wear. Three patients developed late infections. These early results support the
      ongoing use of this design; however, long-term studies will be required.

PMID- 16950034
TI  - Magnetic resonance imaging with metal suppression for evaluation of
      periprosthetic osteolysis after total knee arthroplasty.
AB  - Osteolysis around total knee arthroplasty (TKA) can be difficult to identify and
      quantitate on plain radiographs. This study reports on magnetic resonance imaging
      (MRI) with metal suppression for the evaluation of suspected periprosthetic
      osteolysis around TKA. We retrospectively reviewed 11 patients referred for MRI
      with suspected periprosthetic osteolysis. Radiographic and MRI findings and
      findings at revision arthroplasty were correlated. The presence of osteolysis was
      identified or suspected radiographically in all of the 11 patients. Osteolysis
      was confirmed in 10 patients by MRI. In 9 of 11 patients, the extent of
      osteolysis was greater on MRI than estimated radiographically. In 5 of 11
      patients, MRI demonstrated additional osteolytic lesions which were
      radiographically occult. In one case, the amount of osteolysis on MRI was less
      than on initial radiographs, and in one case, osteolysis was felt to be present
      radiographically but was not confirmed on MRI. In all 7 of 11 patients
      subsequently treated with revision TKA, MRI findings were confirmed at revision.

PMID- 16950035
TI  - Using intraoperative pelvic landmarks for acetabular component placement in total
      hip arthroplasty.
AB  - Dislocation after total hip arthroplasty is frequently due to acetabular
      malpositioning. Positioning of the acetabular component using anatomical
      landmarks may reduce the incidence of dislocation from improper acetabular
      orientation. The pelvis provides 3 bony landmarks (ilium, superior pubic ramus,
      and superior acetabulum), which, when used to define a plane, allows cup
      orientation in abduction and version. Landmarks evaluated in 24 cadaveric
      acetabuli allowed slightly increased abduction and anteversion of the cup,
      compared with native acetabuli. Six hundred seventeen primary total hip
      arthroplasties were performed between 1996 and 2003 using this technique. Mean
      cup abduction was 44.4 degrees with 13.2 degrees of anteversion. This technique
      allows satisfactory reproducible cup orientation based on individual pelvic
      morphology. Review of patient outcome data suggest high patient satisfaction and
      lower dislocation rate without additional equipment, time, or cost.

PMID- 16950036
TI  - Acetabular cement mantles and component position: are we achieving "ideal"
      results?
AB  - Radiographs of 100 primary cemented total hip arthroplasties were studied.
      Acetabular component positioning and cement mantles were assessed with respect to
      implant type, grade of surgeon, and operated side. Seventy-eight percent of the
      components were eccentrically placed, with increasing cement mantle thickness
      from zone 1 to zone 3. Concentricity occurred in only 13% of the Charnley Ogee
      and in 28% of the IP Lubinus components. The Charnley Ogee was more superiorly
      placed than the IP Lubinus (P < .001). Surgical grade affected neither cement
      mantle thickness nor opening angle. In vitro studies ideally recommend concentric
      placement of the acetabular component. This appears difficult to achieve
      consistently in vivo in most patients using the components in this study.

PMID- 16950037
TI  - Early clinical and radiographic analysis of the Fitmore cup.
AB  - The Fitmore titanium mesh cementless acetabular component in 115 hip
      arthroplasties was reviewed at an average of 33 months of follow-up. None were
      revised nor had infection. One hip dislocated 4 years postoperatively. Two
      femoral components were revised. The average Harris Hip Score at the last follow
      up was 90 points. In the 96 sets of radiographs available, there was no loosening
      or new radiolucency. One hip had nonprogressive osteolysis adjacent to a screw.
      This press-fit cup has its polar region flattened and is rim loading. Noncontact
      (gaps) at the acetabular floor is expected and is not critical for fixation. In
      all but 6 hips, these gaps filled. In 5 hips, a minimal gap (<or=0.5 mm) remained
      in part of the equatorial region. The Fitmore cup osseointegrates successfully.

PMID- 16950038
TI  - The incidence of heterotopic ossification after cementless total hip
      arthroplasty.
AB  - The purpose of this study was to determine the incidence of heterotopic
      ossifications (HOs) after total hip arthroplasty in Japanese patients and the
      predisposing factors associated with this condition. One thousand hips of 885
      patients undergoing cementless total hip arthroplasties were examined with
      respect to the incidence and severity of HO; the data analysis was conducted by
      using the univariate and multivariate methods. The overall incidence of HO was
      5.2%, with severe HO in 0.9% of the patients. A significant increase in the
      frequency of HO was observed in patients with ankylosed hips (odds ratio, 11.1;
      95% confidence interval, 2.5-49.9), hypertrophic osteoarthritis (odds ratio, 2.7;
      95% confidence interval, 1.2-5.9), and with a particular type of prosthesis used
      (ceramic-on-ceramic vs ceramic-on-polyethylene) (odds ratio, 2.5; 95% confidence
      interval, 1.3-4.8).

PMID- 16950039
TI  - Management of types III and IV acetabular deficiencies with the longitudinal
      oblong revision cup.
AB  - Thirty-five longitudinal oblong revision (LOR) cups were used to reconstruct 29
      type III and 6 type IV acetabular defects. Intraoperatively, we considered that
      cup contact was complete when we achieved a continuous contact between the cup
      periphery and the acetabular rim. When there were areas with a lack of contact,
      we considered that the contact was partial or incomplete. All patients were
      followed up for 4 to 8 years (mean = 6.3 years). At the latest follow-up, 30 cups
      were stable (85.8%) and 5 had migrated (14.2%). We found a significant relation
      between incomplete cup contact with the acetabular rim and subsequent failure (P
      = .042). The abduction angle was significantly increased in the group of unstable
      cups (P = .032) because of the migration of the acetabular component that became
      more vertical. Pain, limp, use of walking aids, functional level, and limb-length
      discrepancy significantly improved postoperatively (P < .0001). The Harris hip
      score improved from a mean preoperative score of 37 points to that of 79 points
      (P < .01). This implant showed satisfactory stability at early to midterm follow
      up.

PMID- 16950040
TI  - Minimal surgical approach for recurrent hip dislocation using the posterior lip
      augmentation device for the Charnley hip arthroplasty.
AB  - We present the management of recurrent posterior dislocations in cemented
      Charnley total hip arthroplasties treated with acetabular augmentation. Certain
      patients are elderly with comorbid conditions and diminished reserves. We have
      used a minimal surgical approach to implant 21 posterior lip augmentation devices
      in elderly patients. Ninety percent of the hips are stable with follow-up of 1 to
      3 years (mean, 1.9 years). Eighty-four percent of the patients were satisfied
      with the outcome. Two cases, which redislocated, were further stabilized by
      changing the position of the posterior lip augmentation device and are stable.
      Because of a minimal surgical approach, the time duration of surgery, blood loss,
      transfusion requirement, inpatient stay, and morbidity are reduced. Posterior lip
      augmentation device surgery with a minimal approach is a safe and effective
      procedure for elderly patients who do not have any obvious cause for dislocation.

PMID- 16950041
TI  - The use of antifibrinolytic agents in total hip arthroplasty: a meta-analysis.
AB  - Total hip arthroplasty is associated with significant blood loss that often
      requires allogenic blood transfusions. Tranexamic acid and aprotinin have been
      shown to reduce blood loss and transfusions in clinical trials with variable
      results. This meta-analysis evaluates whether tranexamic acid and aprotinin
      significantly reduces blood loss and transfusion requirements in total hip
      arthroplasty. Thirteen clinical trials were identified. Combined, these agents
      were significant across all outcome measures in reducing blood loss and
      transfusions. Separately, only aprotinin was found to be significant. The data
      also showed that aprotinin (tranexamic acid is inconclusive) is only beneficial
      in revision total hip arthroplasty. Therefore, only aprotinin is effective in
      reducing both blood loss and transfusion requirements without an increase in
      thromboembolic complications in patients undergoing revision total hip
      arthroplasty.

PMID- 16950042
TI  - Incidence and timing of myocardial infarction after total joint arthroplasty.
AB  - Retrospective review of 3471 patients who underwent total joint arthroplasty
      (TJA) (1479 hips, 1992 knees) to determine the incidence and timing of inhospital
      myocardial infarction (MI) after TJA. Sixty-three patients (1.8%; 95% CI, 1.4%
      2.4%) suffered a perioperative MI occurring at a mean of 3 days post surgery. In
      multivariate analysis, increased age, body mass index, bilateral TJA, diabetes,
      and American Society of Anesthesiologists rating 3 were associated with
      perioperative MI. Our data cautions against hospital discharge within 3 days of
      surgery.

PMID- 16950043
TI  - Reliability of the transepicondylar axis as an anatomical landmark in total knee
      arthroplasty.
AB  - Femoral component malalignment after total knee arthroplasty is known to cause
      clinical symptoms, such as anterior knee pain. For intraoperative referencing,
      several anatomical landmarks are used by surgeons. One frequently used landmark
      is the transepicondylar axis, yet the accuracy and reproducibility of defining
      this axis have not been established. In 6 human cadavers, 4 different experienced
      orthopedic surgeons performed selections of the most prominent points of the
      medial and lateral epicondyle. Each individual position was digitized and
      recorded by an accurate optical navigation system. In addition, the most
      prominent points of the medial and lateral epicondyle were defined on a computed
      tomography image. After transforming the cadaver points in the computed
      tomography coordinate system, distances to the epicondyles were measured. The
      overall distribution of selected points was located in an area of 278 mm2 upon
      the medial epicondyle and 298 mm2 of the lateral.

PMID- 16950044
TI  - Mechanical bond strength of the cement-tibial component interface in total knee
      arthroplasty.
AB  - The purpose of this study was to mechanically test the cement-tibial component
      interface using titanium and cobalt-chrome sample prostheses with several
      commercially available surface textures. The results of this study indicate that
      the type of metal substrate and surface preparation of contemporary tibial
      baseplates may influence the strength of the metal-cement interface and as such
      influence tibial component survival. The results indicate that, in general, metal
      cement interface strength increases with increasing surface roughness and common
      surface treatments such as AlO2 grit-blasting (Ra = 6.76 microm) produce
      interface strengths similar to plasma-spray, porous-coated specimens.
      Macrosurfaced tibial components, although comparable in tension, may be
      vulnerable to metal-cement interface failure with rotational loading.

PMID- 16950045
TI  - Optimization of the posterior condylar offset, tibial slope, and condylar roll
      back in total knee arthroplasty.
AB  - Total knee arthroplasty does not restore the full range of motion of the knee.
      Retrospective clinical studies on knee kinematics suffer from multiple biases
      because the various parameters involved, that is, the posterior condylar offset,
      the tibial slope, and the condylar roll-back, are not individualized. The present
      study, based on the geometry of knee flexion, shows that a 3-mm decrease of the
      posterior condylar offset could reduce knee flexion by 10 degrees before the
      occurrence of tibiofemoral impingement. In addition, the simultaneous decrease of
      the tibial slope by 5 degrees could reduce the flexion by a further 5 degrees.
      These effects could be reinforced if the paradoxical condylar roll-forward was
      made to exceed 10 mm. Finally, decreasing the condylar offset in a prosthesis
      with a paradoxical roll-forward and a neutral tibial slope could reduce maximum
      obtainable knee flexion before impingement by as much as 30 degrees.

PMID- 16950046
TI  - Proximal femoral geometry: a radiological assessment.
AB  - We aimed to analyze radiographically the relationship between the tip of the
      greater trochanter and the center of the femoral head. One hundred fifty randomly
      selected radiographs of patients due to undergo total hip arthroplasty were
      analyzed for the relationship between the center of the femoral head and the tip
      of the greater trochanter. We found that the center of the femoral head was 9.5
      +/- 6 mm below (9 mm above to 24 mm below) the tip of the greater trochanter.
      Many techniques have been described to diminish the inadvertent limb lengthening
      during total hip arthroplasty. One of the commonly used methods has been
      alignment of the tip of the greater trochanter with the center of the femoral
      head. The aim of the article is to discourage the use of the tip of the greater
      trochanter as guide because it may lead to inadvertent limb lengthening.

PMID- 16950047
TI  - Aging performance of a compliant layer bearing acetabular prosthesis in an ovine
      hip arthroplasty model.
AB  - The wear performance of a polyurethane compliant layer (CL) material formed into
      an acetabular component and implanted into a sheep model of cemented total hip
      arthroplasty was assessed at 6, 12, 24, and 48 months. Four (11%) of 36
      acetabular components debonded from the cement and one component was slightly
      loose at the cement-bone interface. There was no macroscopic evidence of
      fracture, wear, or deformation of the CL material on the articular surface of the
      acetabular components. Small numbers of polymeric wear particles was found in the
      hip synovial tissues of 10 sheep, most commonly in the early time groups, and
      were likely associated with initial wear of surface asperities. The wear
      performance of the CL was unchanged during a 48-month implantation period.

PMID- 16950048
TI  - Acute sciatic nerve palsy caused by a polyethylene granuloma arising from a well
      fixed total knee arthroplasty.
AB  - We report the presentation of an acute sciatic nerve palsy, arising as a result
      of an inflammatory mass in the posterior thigh containing polyethylene debris
      from an adjacent, well-fixed total knee arthroplasty.

PMID- 16950049
TI  - Extracorporeal shockwave treatment of osteonecrosis of the femoral head in
      systemic lupus erythematosis.
AB  - This article reported a case of systemic lupus erythematosis (SLE) with
      osteonecrosis of the femoral heads (ONFH-3) successfully treated with a novel
      extracorporeal shockwave treatment (ESWT). The follow-up at 3 years showed that
      both hips had no pain on activities for daily living. Magnetic resonance image
      (MRI) showed substantial reduction in bone marrow edema and no further collapse
      of the lesions. Radiographs and MRIs showed no change in the staging of the
      disease. ESWT provided beneficial effects for hips affected by ONFH in patients
      with SLE. This novel treatment modality resulted in significant pain relief and
      functional improvement of the hip and reduction in bone marrow edema in our
      patient. It appeared that ESWT might have the potential to curtail the
      progression of the disease and to delay the need for total hip arthroplasty in
      the very young patients contracted with SLE.

PMID- 16950050
TI  - Smith-Petersen mould arthroplasty: an ultra-long-term follow-up.
AB  - We present a case of a Smith-Petersen mould arthroplasty in a 77-year-old man.
      The implant was inserted by Sir John Charnley himself in 1948. The patient is
      pain-free and walks without aids. At 56 years, this case represents the longest
      surviving Smith-Petersen mould arthroplasty with a satisfactory result in the
      current literature.

PMID- 16950051
TI  - A case of disassociation of a modular femoral neck trunion after total hip
      arthroplasty.
AB  - Modular femoral heads offer the advantages of increased intraoperative
      flexibility through the adjustment of leg length and offset, whereas a modular
      femoral neck can also allow independent adjustment of femoral anteversion.
      Despite the potential advantages of hip systems using increased modularity, these
      component designs also offer a greater number of junctions through which problems
      may occur. This case demonstrates the potential for dissociation of a Morse taper
      between a modular femoral neck and stem.

PMID- 16950052
TI  - Intrapelvic migration of a well-fixed femoral stem after removal of an acetabular
      cup.
AB  - Failure of total hip arthroplasty with central migration of prosthetic components
      is uncommon. Various pelvis and visceral complications have been reported from
      intrapelvic migration of the acetabular cup or the cement or from the heat
      generated by methylmethacrylate polymerization. To our knowledge, we are the
      first to report intrapelvic migration of a femoral stem causing ipsilateral lower
      extremity swelling, pressure sores, and severe bowel symptoms after the removal
      of the acetabular component.

PMID- 16950053
TI  - Periprosthetic malignancy as a mode of failure in total hip arthroplasty.
AB  - The presence of periprosthetic malignancy in proximity to arthroplasty implants
      has been infrequently reported. We present the clinical, radiographic, and
      pathological features of three patients in whom loosening and failure of total
      hip arthroplasties occurred secondary to malignant infiltration. They consisted
      of a 66-year-old man with the first presentation of metastatic gastric carcinoma
      as a periacetabular lytic lesion, a 64-year-old man presenting with femoral
      metastases from a previously undiagnosed lung carcinoma, and a 75-year-old woman
      presenting with a painless discharging thigh sinus around a total hip
      arthroplasty subsequently diagnosed as immunoblastic lymphoma. Malignant
      infiltration should be considered part of the differential diagnosis in aseptic
      and septic loosening of prosthetic implants. Joint aspiration and isotope bone
      scanning provide useful additional information before surgical intervention.

PMID- 16950054
TI  - Publication rates of scientific presentations at the American Association of Hip
      and Knee Surgeons annual meetings from 1996 to 2001.
AB  - National orthopedic subspecialty meetings are a research forum where volumes of
      investigations are presented after a peer-reviewed selection process. The
      objective of this investigation was to determine the publication rate of recent
      scientific presentations presented at the American Association of Hip and Knee
      Surgeons (AAHKS) annual meetings. From 1996 to 2001, 168 (58%) of 292 podium
      abstracts presented at meetings were published. The average time to publication
      was 21.7 +/- 14.7 months. Three major orthopedic journals constituted 89% of the
      publications. The 58% publication rate for AAHKS ranks as one of the higher rates
      for orthopedic specialty meetings and validates the selection process for
      abstracts presented. In addition, AAHKS meetings are an excellent source for a
      wide array of quality research and scientific information.

PMID- 16950055
TI  - Medicare reimbursement: an orthopedic primer.
AB  - Since 1992, Medicare has paid physicians and other practitioners by using a
      resource-based relative value scale system (RBRVS). The Center for Medicare
      Services updates the RBRVS annually and reviews the work portion for each
      procedure every 5 years. The calculation of the work units is done by using a
      survey. This survey polls the average amount of time spent in each portion of the
      case. The survey process is quite complex. Some of the specific biases that can
      be found include rank lists, multidimensional, hypothetical items, and complexity
      and memory overload bias. Survey errors are easy to make over and above item
      bias. With this system, surgeons are encouraged to be slower to increase their
      compensation. Surveying methodology is not the most appropriate way to tabulate
      time and work. Unless this methodology changes, orthopedic surgeons will continue
      to be shortchanged.

PMID- 16950056
TI  - Hospital volume and inpatient mortality outcomes of total hip arthroplasty in the
      United States.
AB  - The purpose of this study was to examine the effect of hospital volume on
      outcomes for primary and revision total hip arthroplasty (THA). The Nationwide
      Inpatient Sample database was used to identify our patient set. These data
      include a sample of non-Medicare and Medicare patients who are unique to this
      study, increasing external validity compared with other studies. Outcome
      variables examined included in-hospital mortality and prolonged length of stay
      (PLOS). Primary THA mortality was 0.16% in the highest volume quartile and 0.29%
      in the lowest volume quartile (P < .001). The rates of PLOS showed improved
      outcomes in the highest volume hospitals. Similar trends were found for revision
      THA, with an in-hospital mortality of 1.20% for lowest volume hospitals and 0.48%
      for highest volume hospitals (P < .001). Hospitals with higher volume had
      superior inpatient outcomes mortality, PLOS, and discharge disposition for THA
      and revision arthroplasty.

PMID- 16950057
TI  - A randomized prospective evaluation of outcomes after total hip arthroplasty
      using cross-linked marathon and non-cross-linked Enduron polyethylene liners.
AB  - Cross-linked liners were introduced with the promise that they would
      substantially reduce polyethylene wear. In 1999, our institution initiated a
      prospective study to compare the outcome of total hip arthroplasty patients who
      were randomized to non-cross-linked Enduron liners with that of total hip
      arthroplasty patients who were randomized to Marathon polyethylene liners that
      had been cross-linked with 5 Mrad (50 kGy) of gamma-irradiation and heat-treated
      to eliminate free radicals. At a mean follow-up of 5.7 years, the clinical
      outcomes among the Marathon and Enduron liners were similar. However, the mean
      wear rate was 0.01 +/- 0.07 mm/y for the Marathon group, which represents a 95%
      reduction compared with the mean wear rate of 0.19 +/- 0.12 mm/y for the Enduron
      group. In addition, the incidence of osteolysis was lower in the Marathon group.

PMID- 16950058
TI  - One-stage bilateral total hip arthroplasty compared with unilateral total hip
      arthroplasty: a prospective study.
AB  - It is believed that patients undergoing 1-stage bilateral joint arthroplasty are
      at higher risk for developing cardiopulmonary and possibly other complications.
      The aim of this prospective matched study was to evaluate and compare the
      morbidity profile of patients undergoing 1-stage bilateral uncemented total hip
      arthroplasty (BTHA) vs unilateral uncemented THA (UTHA). One hundred consecutive
      patients undergoing 1-stage bilateral THA (50 patients, 100 hips) and unilateral
      THA (50 patients) were recruited and prospectively followed. There were no
      statistically significant differences in 90-day mortality, individual major
      (BTHA, 8%; UTHA, 10%) or minor (BTHA, 20%; UTHA, 26%) complications between the 2
      groups. Bilateral THA patients required more autologous and allogenic blood
      transfusion and had lower hemoglobin at discharge than UTHA patients. Patients
      undergoing BTHA should expect a slightly higher incidence of complications
      related to postoperative anemia.

PMID- 16950059
TI  - Tapered titanium porous plasma-sprayed femoral component in patients aged 40
      years and younger.
AB  - Total hip arthroplasty (THA) in patients aged 40 years and younger requires
      decades of increased activity demands. Between 1987 and 2000, 249 primary THAs in
      patients 40 years of age or younger were performed with the Mallory-Head
      component. The average age at THA was 34.7 years (range, 20-40 years). Follow-up
      averaged 91 months with 125 hips having minimum 5-year follow-up and 51 THAs
      having a minimum of 10 years. Four stems failed the 98.2% overall survivorship.
      Two stems were revised for loosening for a 99.2% (95% confidence interval, 96.4%
      99.8%) survivorship with aseptic loosening as the end-point at 18 years. In young
      patients, this tapered titanium, proximally porous plasma-sprayed femoral
      component provides outstanding long-term fixation and function with significant
      pain relief into the second decade. Overall stem survivorship is 98.2% at up to
      18 years.

PMID- 16950060
TI  - Hip arthroplasty with minimally invasive surgery: a survey comparing the opinion
      of highly qualified experts vs patients.
AB  - In recent years, there has been an increasing debate regarding the possible role
      of minimally invasive (MIS) total hip arthroplasty (THA). We conducted a
      questionnaire survey of the Hip Society members and compared the responses of the
      surgeons with those of patients who were being considered for THA. 80% of
      surgeons who completed the survey admitted to performing MIS THA, of whom two
      thirds defined MIS as small incision. Of surgeons, 74% had encountered some
      complication related to MIS THA; 67% of patients had not heard of MIS THA. The
      knowledge regarding MIS THA expressed by 80% of patients was either inaccurate or
      not substantiated by any studies. This survey highlights the inadequacy of our
      current understanding of MIS THA and lack of education on the part of the
      patients.

PMID- 16950061
TI  - Serum metal levels and bearing surfaces in total hip arthroplasty.
AB  - This study evaluates steady-state serum metal levels in patients with 4 different
      combinations of fixation modalities, materials, and bearing couples. Forty
      patients with a minimum of 5 years of follow-up and with well-functioning primary
      total hip arthroplasty were recruited to have serum metal levels measured. Serum
      chromium and cobalt levels in the metal-on-metal cohort were significantly higher
      (P < .05) than the other 3 cohorts. The noncemented ceramic-polyethylene cohort
      had significantly lower (P < .05) serum chromium levels compared to cemented and
      noncemented metal-polyethylene cohorts and significantly higher serum titanium
      levels compared to the cemented metal-polyethylene cohort which had no titanium
      containing implants. Debris generated at the metal head/neck modular junction
      likely accounts for the significantly lower serum chromium concentration in
      ceramic-polyethylene bearing couples.

PMID- 16950062
TI  - Long-term outcome and risk factors of proximal femoral fracture in uncemented and
      cemented total hip arthroplasty in 2551 hips.
AB  - Proximal femoral fractures are relatively common during total hip arthroplasty.
      The purposes of this study were to identify risk factors associated with femoral
      fractures and determine their effect on femoral stem survivorship. A total of
      2551 hips were examined with up to 16 years of follow-up (mean, 6.8 years).
      Seventy-five percent of the stems were cemented. The incidence of proximal
      femoral fracture was 2.3% (59 hips). Risk factors associated with fractures
      include anterolateral approach, uncemented femoral fixation, and female sex (P <
      .01). Cerclage wiring was the most common treatment. After a fracture, femoral
      component survivorship was 95.8% for uncemented stems and 91.7% for cemented
      stems. In the absence of fracture, stem survivorship was 98.6% for cemented stems
      and 100% for circumferentially coated tapered titanium uncemented stems.

PMID- 16950063
TI  - Ninety-day mortality after hip arthroplasty: a comparison between unilateral and
      simultaneous bilateral procedures.
AB  - This study compares the 90-day mortality of unilateral total hip arthroplasty
      (THA) with simultaneous bilateral THA. Patient demographics, cause of death, and
      risk factors for mortality after THA were investigated. A total of 6258 patients
      (6791 hips) received primary THA using uncemented prostheses from 1995 to 2002.
      There were 5725 (91%) patients who received unilateral THA, whereas 533 (9%)
      patients underwent simultaneous bilateral THA. Of 6258 patients, 10 (0.16%) died
      within 90 days of THA, none of whom underwent simultaneous bilateral THA (0%,
      0/533). Simultaneous bilateral uncemented THA performed in a select group of
      patients carries no greater perioperative mortality rate than unilateral THA.

PMID- 16950064
TI  - Does neck/liner impingement increase wear of ultrahigh-molecular-weight
      polyethylene liners?
AB  - We explore the hypothesis that repetitive impingement increases wear of ultrahigh
      molecular-weight polyethylene inserts. During revision total hip arthroplasty,
      113 acetabular components were retrieved and examined for impingement, backside
      wear, and articular wear. Sixty percent of acetabular liners showed evidence of
      prosthetic impingement, with moderate or severe damage to the rim in 32%.
      Moderate or severe backside damage was present in 31%. Backside wear was found in
      61% (22/36) of liners exhibiting impingement vs 16% (12/73) of liners without
      impingement (P < .0001). The average articular wear rate of liners with
      moderate/severe impingement damage was 159 +/- 42 mm(3)/y, compared with 70 +/-
      21 mm(3)/y for liners with no/mild impingement damage (P = .02). Repetitive
      impingement frequently occurs after total hip arthroplasty and leads to a
      multitude of adverse events, including motion between the liner and the
      acetabular shell.

PMID- 16950065
TI  - Acetabular component deformation with press-fit fixation.
AB  - Acetabular component deformation secondary to forces encountered during insertion
      is a potential consequence of the press-fit technique. This study characterized
      the stiffness of Pinnacle 100 cups (DePuy, Warsaw, Ind) via mechanical testing
      and used this information with intraoperative measurements of cup deformation to
      calculate the in vivo forces acting on cups inserted during hip arthroplasty in
      21 patients. We found that 90.5% of cups had measurable compression deformity,
      averaging 0.16 +/- 0.16 mm. The corresponding forces acting on these cups
      averaged 414 +/- 421 N. For hard-on-hard bearing surfaces, such in vivo
      deformation of acetabular shells may result in negative clinical consequences
      such as equatorial loading with increased wear and potential seizing of
      components, chipping of ceramic inserts, or locking mechanism damage.

PMID- 16950066
TI  - Computed tomographic follow-up evaluation of operative intervention for
      periacetabular lysis.
AB  - Computed tomography (CT) accurately evaluates periacetabular lytic lesions. The
      purpose of this study is to determine the fate of osteolytic lesions after
      treatment with liner exchange and bone grafting. Fifteen patients who had
      undergone liner exchange with grafting for progressive lytic lesions, as
      demonstrated by preoperative CT scans, were identified. Postoperative CT scans
      were performed at a minimum of 2 years post revision. The largest cross sectional
      lytic area was compared with the postoperative scan to determine the fate of the
      lesion. The mean size of the measured lytic lesions preoperatively was 6.38
      cm(2). Postoperatively, lesions decreased to 2.94 cm(2) (P = .000). Modular liner
      exchange with grafting is effective in treating osteolytic lesions in the pelvis,
      as demonstrated by CT.

PMID- 16950067
TI  - The use of a trabecular metal acetabular component and trabecular metal augment
      for severe acetabular defects.
AB  - Stable acetabular fixation cannot be reliably achieved with the use of a
      hemispherical porous coated component alone in patients with a Paprosky type IIIa
      defect. The purpose of the present study was to determine the short-term results
      of a tantalum porous coated hemispherical acetabular component supported with a
      modular tantalum augment in Paprosky type IIIa defects. A total of 28 patients
      (28 hips) were treated for a type IIIa acetabular defect between 2001 and 2003
      with the use of a trabecular metal acetabular component supported with a modular,
      superiorly placed trabecular metal augment. At an average of 3.1 years follow-up,
      1 patient required rerevision for recurrent instability. The remaining hips
      remain radiographically stable. Clinically, the patients' modified Postel Merle
      d'Aubigne score improved from 6.8 preoperatively to 10.6 postoperatively. The use
      of a trabecular metal acetabular component with a superiorly placed trabecular
      metal augment demonstrates encouraging short-term results for Paprosky type IIIa
      acetabular defects.

PMID- 16950068
TI  - Acetabular revision using a trabecular metal acetabular component for severe
      acetabular bone loss associated with a pelvic discontinuity.
AB  - Pelvic discontinuity can be encountered during acetabular revision in patients
      with severe bone loss. All patients who had an acetabular reconstruction for a
      type IIIB acetabular defect according to the classification of Paprosky et al
      [Paprosky WG, Perona PG, Lawrence JM. 1994. Acetabular defect classification and
      surgical reconstruction in revision arthroplasty. A 6-year follow-up evaluation.
      J Arthroplasty 9:33.] with an associated pelvic discontinuity between 2001 and
      2003 were reviewed. A trabecular metal acetabular component with or that without
      an acetabular augment was used to obtain fixation proximal and distal to the
      discontinuity. Thirteen patients (13 hips) were treated for a type IIIB
      acetabular defect. At an average of 2.6 years of follow-up, 1 patient
      demonstrated possible radiographic loosening. The other 12 patients maintained
      radiographically stable hips. None of the patients required repeat surgical
      intervention. Clinically, the patients' modified Postel-Merle d'Aubigne score
      improved from 6.1 preoperatively to 10.3 postoperatively. The treatment of pelvic
      discontinuity during acetabular revision using a trabecular metal acetabular
      component with or that without an associated trabecular metal augment appears to
      provide reliable and reproducible short-term results.

PMID- 16950069
TI  - Comparison of fluorodeoxyglucose positron emission tomography and (111)indium
      white blood cell imaging in the diagnosis of periprosthetic infection of the hip.
AB  - We aimed to compare the accuracy of fluorodeoxyglucose positron emission
      tomography (FDG-PET) with technetium-99m sulfur colloid (111)indium-labeled white
      blood cell scintigraphy (TcSC-Ind BM/WBC) in diagnosis of periprosthetic
      infection. Eighty-nine patients with 92 painful hip prostheses were recruited
      prospectively and given the option of undergoing either combined FDG-PET and TcSC
      Ind BM/WBC or FDG-PET only. FDG-PET correctly diagnosed 20 of the 21 infected
      cases (sensitivity, 95.2%) and ruled out infection in 66 of the 71 aseptic hips
      (specificity, 93%) corresponding to a positive predictive value of 80% (20/25)
      and a negative predictive value of 98.5% (66/67). TcSC-Ind BM/WBC correctly
      identified 5 of the 10 infected cases (sensitivity, 50%) and 39 of 41 aseptic
      cases (specificity, 95.1%) corresponding to a positive and negative predictive
      values of 41.7% (5/12 cases) and 88.6% (39/44 cases), respectively. Based on
      these preliminary results, FDG-PET appears to be a promising diagnostic tool for
      distinguishing septic from aseptic painful hip prostheses.

PMID- 16950070
TI  - Incidence and reasons for reoperation after minimally invasive unicompartmental
      knee arthroplasty.
AB  - The goal of this report is to review reoperations undertaken on the initial 221
      unicompartmental arthroplasties performed using a minimally invasive technique. A
      comparison was then performed between these cases and the previous 514 open
      medial unicompartmental arthroplasties performed at our institution. In the
      minimally invasive group, 9 (4.1%) of 221 knees were revised (8 for component
      loosening, 1 for deep infection). Of 212 unrevised knees, 16 have required a
      total of 18 nonrevision reoperations. Overall, 25 of 221 knees required at least
      1 reoperation (total reoperation rate, 11.3%). Despite an accelerated recovery
      and decreased hospital stay in our minimally invasive unicompartmental
      arthroplasties, the rate of revision due to aseptic loosening (3.7% vs 1.0%) and
      the overall reoperation rate (11.3% vs 8.6%) compare unfavorably with those
      performed with an open technique.

PMID- 16950071
TI  - Patient, implant, and alignment factors associated with revision of medial
      compartment unicondylar arthroplasty.
AB  - The investigators reviewed 245 fixed-bearing unicondylar arthroplasties that one
      surgeon performed as treatment of medial compartment osteoarthritis between 1988
      and 1997 using a variety of cemented metal-backed tibial components and gamma
      irradiated-in-air polyethylene bearings. Multivariate statistical analysis was
      used to evaluate how the event of revision was influenced by 3 patient factors, 3
      implant factors, and 7 factors assessed from preoperative and early postoperative
      radiographs. Five factors were statistically associated with revision: (younger)
      patient age, (thinner) tibial component initial thickness, (longer) polyethylene
      shelf age, (lesser) angular reduction of medial tibial plateau varus, and (more
      varus) postoperative hip-knee-ankle angle. Besides illustrating deleterious
      consequences of using gamma-irradiated-in-air polyethylene in medial
      unicompartmental arthroplasty, our results support reducing varus angulation of
      the medial tibial plateau and knee at surgery.

PMID- 16950072
TI  - The effect of the Insall-Salvati ratio on outcome after total knee arthroplasty.
AB  - The effect of total knee arthroplasty (TKA) on the Insall-Salvati ratio (ISR) and
      the effect of the ISR on the outcome of TKA have not been clearly established. A
      retrospective review of 1055 primary TKAs performed in 1997 to 1998 was
      performed. Radiographic measurements were made preoperatively and
      postoperatively, and the ISR was calculated. Regression analysis was performed to
      determine the effects of these variables on range of motion (ROM), Knee Society
      Score, and stair, function, and pain scores. Total knee arthroplasty resulted in
      a decrease in the patella tendon length, as measured by the ISR in 50% of cases.
      Patella infera (ISR less than 0.8) developed postoperatively in 9.8% of TKAs and
      was twice as likely to occur in women as men. A decrease in the ISR was
      associated with diminished stair and function scores (P = .0004 and 0.0081,
      respectively). There was no effect of the ISR upon ROM, Knee Society Score, or
      pain scores. Optimal outcomes occurred in patients where the ISR was not
      decreased after TKA, with superior stair and function scores.

PMID- 16950073
TI  - Correcting lateral patellar tilt at the time of total knee arthroplasty can
      result in overuse of lateral release.
AB  - Ninety-nine patients undergoing primary total knee arthroplasty were
      prospectively evaluated for pre-resurfacing and post-resurfacing patellar
      thickness and medial patellar liftoff at 30 degrees of flexion without manual
      pressure on the patella. Regardless of medial patellar liftoff, no lateral
      releases were performed. Tibiofemoral angles, patellar tilt, and patellar
      congruence angles were measured preoperatively and postoperatively. There were no
      patellar subluxations, dislocations, or complications related to the
      patellofemoral joint. Patellar tilt improved from 7.9 degrees preoperatively to
      3.8 degrees postoperatively. Patients with 10 mm or more of intraoperative
      liftoff improved from 9.9 degrees tilt preoperatively to 6.6 degrees
      postoperatively. Patients with no intraoperative liftoff had a change from 6.3
      degrees to 2.9 degrees . Although the 2 groups were statistically different, the
      amount of change in alignment was not different between the groups. Patients with
      medial patellar liftoff at the time of arthroplasty do not appear to require
      lateral release to yield acceptable postoperative patellofemoral alignment.

PMID- 16950074
TI  - Posterior cruciate ligament substitution is not essential for excellent
      postoperative outcomes in total knee arthroplasty.
AB  - The study compared postoperative range of motion (ROM) and functional outcome of
      total knee arthroplasty (TKA) with a posterior cruciate ligament (PCL)
      substituting knee prosthesis compared with an ultracongruent PCL-sacrificing
      design. Two hundred nine patients underwent primary TKA. Posterior stabilized
      design (121) and highly conforming, PCL-sacrificing, ultracongruent design (88)
      TKAs were reviewed. Surgeon, surgical approach, and a hyperflexion postoperative
      rehabilitation protocol were the same. Results showed significant improvement in
      knee flexion, ROM, Knee Score, and Function Score within each group.
      Postoperative mean total ROM was slightly higher with the posterior stabilized
      design. The 2 groups were the same postoperatively in the improvement in ROM,
      Knee Score, Function Score, satisfaction level, among other activity metrics.
      There was no clear evidence proving superiority and the need for posterior
      stabilization in PCL-sacrificing TKA.

PMID- 16950075
TI  - The effect of a new multimodal perioperative anesthetic regimen on postoperative
      pain, side effects, rehabilitation, and length of hospital stay after total joint
      arthroplasty.
AB  - This study evaluated the effect of a new multimodal perioperative anesthetic and
      pain management strategy for primary total hip (THA) and total knee arthroplasty
      (TKA). Two cohorts of 50 consecutive THA and 50 TKA patients from before and
      after initiation of the new protocol were compared. The protocol involved
      scheduled oral narcotics, cyclooxygenase-2 inhibitors, no intrathecal narcotics,
      femoral nerve catheters for TKAs, and local anesthetic wound infiltration. Use of
      patient-controlled analgesia was discouraged. Physical therapy was attempted on
      the day of surgery. The demographic data, surgical procedure, and implants were
      similar. There were statistically significant improvements after the protocol
      regarding rest-pain scores post-operative day (POD) 1 and 2, total narcotic
      consumption, distance walked POD 1 and 2, and length of stay. There were no
      significant differences in complications. Implementation of this new multimodal
      perioperative protocol combined with early mobilization for TKA and THA patients
      has shortened length of stay, improved pain control, and accomplished therapy
      goals sooner with less narcotic consumption.

PMID- 16950076
TI  - VenaFlow plus Lovenox vs VenaFlow plus aspirin for thromboembolic disease
      prophylaxis in total knee arthroplasty.
AB  - Two hundred seventy-five patients undergoing unilateral total knee arthroplasty
      were prospectively randomized to receive spinal epidural anesthesia (SEA), a
      VenaFlow calf compression device, and enoxaparin (group A) or SEA, VenaFlow, and
      aspirin (group B). Aspirin was started on the day of surgery, whereas enoxaparin
      was started 48 hours after surgery. Anticoagulants were continued for 4 weeks
      after surgery. All patients had an in-hospital ultrasound screening test on
      postoperative days 3 to 5 and a second follow-up ultrasound 4 to 6 weeks after
      surgery. The overall deep venous thrombosis rates in groups A and B were 14.1%
      and 17.8% (P = not significant), respectively. When used in combination with
      pneumatic compression devices and SEA, enoxaparin was not superior to aspirin in
      preventing deep venous thrombosis after total knee arthroplasty.

PMID- 16950077
TI  - Postdischarge costs in arthroplasty surgery.
AB  - Postdischarge costs associated with primary arthroplasty surgeries have received
      limited attention in the literature. Our objective was to identify the costs
      incurred after discharge in primary arthroplasty and to estimate annual
      postdischarge expenditures in the United States. A cohort of 136 patients who
      underwent primary arthroplasty was studied. Comprehensive rehabilitation unit
      (CRU) and home care (HC) costs were obtained. The National Hospital Discharge
      Survey 2003 data were used to model the national discharge cost estimates. Local
      patient-oriented outcome was also compared in the patients discharged to CRU vs
      HC. Total costs were significantly lower in patients discharged directly to home
      vs those sent to the CRU and who subsequently received HC ($2405 vs $13435, P <
      .001); both patient groups experienced similar quality of life improvements. An
      estimated $3.2 billion is spent annually on postsurgical rehabilitation after
      arthroplasty. Postdischarge costs are significantly higher for patients going to
      a CRU vs those discharged home; yet, both groups had comparable short-term
      outcomes.

PMID- 16950078
TI  - Predictors of discharge to an inpatient extended care facility after total hip or
      knee arthroplasty.
AB  - Increased emphasis has been placed on hospital length of stay and discharge
      planning after total joint arthroplasty (TJA). The purpose of this study was to
      identify baseline patient characteristics that are predictive of discharge to an
      inpatient extended care facility (ECF) after TJA. Clinical, demographic, and
      resource utilization data were analyzed for 7818 consecutive patients who
      underwent primary or revision TJA at 1 of 3 high-volume TJA centers. A stepwise
      linear regression model was used to identify predictors of discharge to an ECF.
      Overall, 29% of patients were discharged to an ECF after TJA. Older age, higher
      American Society of Anesthesiologists class, Medicare insurance, and female sex
      were all associated with a higher likelihood of discharge to an ECF. Significant
      differences in practice patterns were found across hospitals with respect to
      discharge disposition after TJA. Further study is necessary to determine the
      appropriate criteria for discharge to an ECF after TJA.

PMID- 16950079
TI  - Pilot study of methods to document quantity and variation of independent patient
      exercise and activity after total knee arthroplasty.
AB  - Variation in patients' independent exercise and activity after total knee
      arthroplasty (TKA) surgery may contribute to variable functional gains but have
      never been quantified. We pilot tested daily exercise logs and step activity
      monitors to quantify exercise and general home activity post-TKA. Patients
      successfully maintained logs and wore activity monitors. Logs documented
      significant variation in quantity of daily exercises. Women with poor emotional
      health recorded fewer repetitions and greater variation. More daily exercise
      repetitions correlated with larger 6-month functional improvement. Activity peaks
      on step monitors correlated with logged exercise sessions. However, most step
      activity was in addition to exercise sessions. Further research is needed to
      validate these findings and to clarify the relationship among post-TKA exercise,
      activity, and functional gain.

PMID- 16950080
TI  - Thyroid nodules: does the suspicion for malignancy really justify the increased
      thyroidectomy rates?
AB  - Thyroid nodules are frequently diagnosed today, mainly due to the wide use of
      neck ultrasonography (US). The majority of these are benign; suspicion for
      malignancy is an indication for surgery, while benign thyroid nodules may be
      managed conservatively. There is evidence that a large percentage of patients
      with thyroid nodules (many diagnosed incidentally) are over-treated. Careful and
      accurate identification of patients with thyroid nodules highly suspicious for
      underlying malignancy would allow a more reasonable therapeutic approach and
      would result in a reduction of the number of unnecessary thyroidectomies. Fine
      needle aspiration cytology (FNAC), in conjunction with high-resolution thyroid
      US, are currently the most accurate and cost-effective diagnostic approach for
      the evaluation of patients with nodular thyroid disease. Radionuclide thyroid
      scanning should be used selectively. By increasing the use of FNAC, it is
      expected that the number of unnecessary thyroidectomies will be further
      diminished, thereby avoiding over-treatment, without exposing the patients to the
      risk of under-treatment for a highly curable cancer. However, accurate
      preoperative diagnosis of thyroid cancer within a thyroid nodule is not always
      possible and, although the problem of unnecessary surgery can further be
      diminished, it cannot be completely eliminated.

PMID- 16950081
TI  - MRSA endocarditis--postcardiac surgery.

PMID- 16950082
TI  - Spite.

PMID- 16950083
TI  - Sex ratios and social evolution.

PMID- 16950084
TI  - Road crossing in chimpanzees: a risky business.

PMID- 16950085
TI  - Minimal plastid genome evolution in the Paulinella endosymbiont.

PMID- 16950086
TI  - Cell signalling: changing shape changes the signal.
AB  - Recent experiments have revealed the existence of subcellular gradients of
      signalling molecules. A new modelling study shows that changes in cell shape or
      size allow gradient-controlled pathways to be turned on or off simply by altering
      the distance between the signal source and targets.

PMID- 16950087
TI  - Parenting behaviour: babbling bird teachers?
AB  - One of humankind's most distinctive characteristics is our extended and complex
      period of child dependency. New research on a noisy African bird may help to shed
      light on how our unusual parenting behavior evolved.

PMID- 16950088
TI  - Chromosome segregation: correcting improperly attached chromosomes.
AB  - Two new studies show that Aurora B kinase corrects improperly attached
      chromosomes by recruiting molecules necessary for eliminating the bad attachments
      and by regulating the turnover of the kinetochore fiber.

PMID- 16950089
TI  - Marine ecology: gelatinous bells may ring change in marine ecosystems.
AB  - Gelatinous plankton are critical components of marine ecosystems. Recent studies
      are providing evidence of increased population outbursts of such species.
      Jellyfish seem to respond when an ecosystem is over-fished, and their ecology is
      under-researched.

PMID- 16950091
TI  - Replication termination: mechanism of polar arrest revealed.
AB  - The Tus-Ter protein-DNA complex of Escherichia coli blocks progression of DNA
      replication from only one direction at the replication terminus. As the
      replication fork helicase unwinds one side of Ter, a conserved cytosine flips out
      of the duplex and binds to Tus, thereby creating a locked complex that blocks the
      advancing helicase.

PMID- 16950090
TI  - Behavioral endocrinology: lighting up peptidergic neurons that mediate a complex
      behavior.
AB  - A recent study in which a calcium-sensitive fluorescent protein was expressed in
      transgenic Drosophila has shown that a command neuropeptide that turns on a
      complex behavioral sequence elicits a spatially and temporally complex pattern of
      neuropeptide signals.

PMID- 16950092
TI  - Animal cognition: know your enemy.
AB  - Food-storing corvids are able to remember which individual saw them store food,
      and take preventive action that is tailored to that particular competitor's
      knowledge. This raises the question of whether abilities like 'theory of mind'
      have arisen independently more than once in evolution.

PMID- 16950093
TI  - Liver specification: a new role for Wnts in liver development.
AB  - Secreted Wnt proteins control a diverse array of developmental decisions. A
      recent analysis of the zebrafish mutant prometheus points to a previously unknown
      role for Wnts during liver specification.

PMID- 16950094
TI  - Endosymbiosis: double-take on plastid origins.
AB  - Plastids--the light-harvesting machines of plant and algal cells--evolved from
      cyanobacteria inside a eukaryotic host more than a billion years ago. New data
      reveal that a mysterious unicellular alga acquired its photosynthetic apparatus
      much more recently than other eukaryotes, affording a second look at the primary
      endosymbiotic origin of plastids.

PMID- 16950095
TI  - The evolutionary biology of sex.
AB  - In 1861, Charles Darwin wrote "We do not even in the least know the final cause
      of sexuality; why new beings should be produced by the union of the two sexual
      elements, instead of by a process of parthenogenesis". It was hardly possible to
      begin to answer this question at that time, in view of the contemporary lack of
      knowledge of genetics and cell biology. Since then, research into the cellular
      basis of reproduction has shown that sexual reproduction is the norm for the
      majority of eukaryotes, with huge consequences for their biology. The evolution
      of sex and some of its consequences are the subject of the series of reviews, and
      a Primer, in this special issue of Current Biology.

PMID- 16950096
TI  - Evolution of sex: why do organisms shuffle their genotypes?
AB  - Sexual processes alter associations among alleles. To understand the evolution of
      sex, we need to know both the short-term and long-term consequences of changing
      these genetic associations. Ultimately, we need to identify which evolutionary
      forces--for example, selection, genetic drift, migration--are responsible for
      building the associations affected by sex.

PMID- 16950097
TI  - Of what use is sex to bacteria?
AB  - Though bacteria are predominantly asexual, the genetic information in their
      genomes can be expanded and modified through mechanisms that introduce DNA from
      outside sources. Bacterial sex differs from that of eukaryotes in that it is
      unidirectional and does not involve gamete fusion or reproduction. The input of
      DNA during bacterial sex generates diversity in two ways--through the alteration
      of existing genes by recombination and through the introduction of novel
      sequences--and each of these processes has been shown to aid in the survival and
      diversification of lineages.

PMID- 16950098
TI  - Sexual reproduction and the evolution of microbial pathogens.
AB  - Three common systemic human fungal pathogens--Cryptococcus neoformans, Candida
      albicans and Aspergillus fumigatus--have retained all the machinery to engage in
      sexual reproduction, and yet their populations are often clonal with limited
      evidence for recombination. Striking parallels have emerged with four protozoan
      parasites that infect humans: Toxoplasma gondii, Trypanosoma brucei, Trypanosoma
      cruzi and Plasmodium falciparum. Limiting sexual reproduction appears to be a
      common virulence strategy, enabling generation of clonal populations well adapted
      to host and environmental niches, yet retaining the ability to engage in sexual
      or parasexual reproduction and respond to selective pressure. Continued
      investigation of the sexual nature of microbial pathogens should facilitate both
      laboratory investigation and an understanding of the complex interplay between
      pathogens, hosts, vectors, and their environments.

PMID- 16950099
TI  - Evolution of plant breeding systems.
AB  - Breeding systems are important, and often neglected, aspects of the natural
      biology of organisms, affecting homozygosity and thus many aspects of their
      biology, including levels and patterns of genetic diversity and genome evolution.
      Among the different plant mating systems, it is useful to distinguish two types
      of systems: 'sex systems', hermaphroditic versus male/female and other
      situations; and the 'mating systems' of hermaphroditic populations, inbreeding,
      outcrossing or intermediate. Evolutionary changes in breeding systems occur
      between closely related species, and some changes occur more often than others.
      Understanding why such changes occur requires combined genetical and ecological
      approaches. I review the ideas of some of the most important theoretical models,
      showing how these are based on individual selection using genetic principles to
      ask whether alleles affecting plants' outcrossing rates or sex morphs will spread
      in populations. After discussing how the conclusions are affected by some of the
      many relevant ecological factors, I relate these theoretical ideas to empirical
      data from some of the many recent breeding system studies in plant populations.

PMID- 16950100
TI  - Relationships between vertebrate ZW and XY sex chromosome systems.
AB  - The peculiar cytology and unique evolution of sex chromosomes raise many
      fundamental questions. Why and how sex chromosomes evolved has been debated over
      a century since H.J. Muller suggested that sex chromosome pairs evolved
      ultimately from a pair of autosomes. This theory was adapted to explain
      variations in the snake ZW chromosome pair and later the mammal XY. S. Ohno
      pointed out similarities between the mammal X and the bird/reptile Z chromosomes
      forty years ago, but his speculation that they had a common evolutionary origin,
      or at least evolved from similar regions of the genome, has been undermined by
      comparative gene mapping, and it is accepted that mammal XY and reptile ZW
      systems evolved independently from a common ancestor. Here we review evidence for
      the alternative theory, that ZW<-->XY transitions occurred during evolution,
      citing examples from fish and amphibians, and probably reptiles. We discuss new
      work from comparative genomics and cytogenetics that leads to a reconsideration
      of Ohno's idea and advance a new hypothesis that the mammal XY system may have
      arisen directly from an ancient reptile ZW system.

PMID- 16950101
TI  - Evolutionary conflicts of interest between males and females.
AB  - Sexual conflict arises from differences in the evolutionary interests of males
      and females and can occur over traits related to courtship, mating and
      fertilisation through to parental investment. Theory shows that sexual conflict
      can lead to sexually antagonistic coevolution (SAC), where adaptation in one sex
      can lead to counter-adaptation in the other. Thus, sexual conflict can lead to
      evolutionary change within species. In addition, SAC can--through its effects on
      traits related to the probability of mating and of zygote formation--potentially
      lead to reproductive isolation. In this review, I discuss that, although sexual
      conflict is ubiquitous, the actual expression of sexual conflict leading to SAC
      is less frequent. The balance between the benefits and costs of the manipulation
      of one sex by the other, and the availability of mechanisms by which conflict is
      expressed, determine whether actual sexual conflict is likely to occur. New
      insights address the relationship between sexual conflict and conflict
      resolution, adaptation, sexual selection and fitness. I suggest that it will be
      useful to examine systematically the parallels and contrasts between sexual and
      other evolutionary conflicts. Understanding why some traits, but not others, are
      subject to evolutionary change by SAC will require data on the mechanisms of the
      traits involved and on the relative benefits and costs of manipulation and
      resistance to manipulation.

PMID- 16950102
TI  - Sexual selection and condition-dependent mate preferences.
AB  - The last decade has witnessed considerable theoretical and empirical
      investigation of how male sexual ornaments evolve. This strong male-biased
      perspective has resulted in the relative neglect of variation in female mate
      preferences and its consequences for ornament evolution. As sexual selection is a
      co-evolutionary process between males and females, ignoring variation in females
      overlooks a key aspect of this process. Here, we review the empirical evidence
      that female mate preferences, like male ornaments, are condition dependent. We
      show accumulating support for the hypothesis that high quality females show the
      strongest mate preference. Nonetheless, this is still an infant field, and we
      highlight areas in need of more research, both theoretical and empirical. We also
      examine some of the wider implications of condition-dependent mating decisions
      and their effect on the strength of sexual selection.

PMID- 16950103
TI  - Control of male sexual behavior in Drosophila by the sex determination pathway.
AB  - Understanding how genes influence behavior, including sexuality, is one of
      biology's greatest challenges. Much of the recent progress in understanding how
      single genes can influence behavior has come from the study of innate behaviors
      in the fruit fly Drosophila melanogaster. In particular, the elaborate courtship
      ritual performed by the male fly has provided remarkable insights into how the
      neural circuitry underlying sexual behavior--which is largely innate in flies--is
      built into the nervous system during development, and how this circuitry
      functions in the adult. In this review we will discuss how genes of the sex
      determination pathway in Drosophila orchestrate the developmental events
      necessary for sex-specific behaviors and physiology, and the broader lessons this
      can teach us about the mechanisms underlying the development of sex-specific
      neural circuitry.

PMID- 16950104
TI  - Potential for control of signaling pathways via cell size and shape.
AB  - BACKGROUND: In order for signals generated at the plasma membrane to reach
      intracellular targets, activated messengers, such as G proteins and
      phosphoproteins, must diffuse through the cytoplasm. If the deactivators of these
      messengers, GTPase activating proteins (GAPs) and phosphatases, respectively, are
      sufficiently active in the cytoplasm, then the signal could in principle decay
      before reaching the target and a stable spatial gradient in phosphostate would be
      generated. Recent experiments document the existence of such gradients in living
      cells and suggest a role for them in mitotic spindle morphogenesis and cell
      migration. However, how such systems behave theoretically when embedded in a cell
      of varying size or shape has not been considered. RESULTS: Here we use a simple
      mathematical model to explore the theoretical consequences of a plasma membrane
      bound activator (i.e., guanine nucleotide exchange factor, GEF, or kinase) and a
      cytoplasmic deactivator (i.e., GAP or phosphatase), and we find that as a model
      cell grows, the substrate becomes progressively dephosphorylated as a result of
      decreased proximity to the activator. Conversely, as a cell spreads and flattens,
      the substrate becomes globally phosphorylated because of increased proximity of
      the substrate to the activator. Similarly, in the leading edge of polarized cells
      and in protrusions such as lamellipodia or filopodia, the substrate is highly
      phosphorylated. As a specific test of the model, we found that the experimentally
      observed preferential activation of the G protein Cdc42 in the periphery of
      fibroblasts that was recently reported is consistent with model predictions.
      CONCLUSIONS: We conclude that cell-signaling pathways can theoretically be turned
      on and off, both locally and globally, in response to alterations in cell size
      and shape.

PMID- 16950105
TI  - Expression profile of a degenerating neo-y chromosome in Drosophila.
AB  - BACKGROUND: Gene-poor, degenerate Y chromosomes have evolved repeatedly from
      ordinary autosomes, but little is known about the processes that silence most
      genes on an evolving Y. RESULTS: Here, I quantify relative expression levels of
      58 gene pairs on the recently formed neo-sex chromosomes of Drosophila miranda,
      in order to test competing models of gene inactivation on its newly evolving Y
      chromosome (the neo-Y). Although the neo-Y of D. miranda still contains the
      majority of its original genes, most exhibit an accelerated rate of protein
      evolution, and many contain frameshift or nonsense mutations. All but three of
      these genes show significantly different levels of expression from the neo-X and
      neo-Y chromosome, with approximately 80% of all genes being expressed at lower
      levels from the neo-Y. The downregulation of many genes on the neo-Y appears to
      occur randomly, regardless of the level of accumulation of amino acid
      substitutions or whether the gene produces a functional protein. In addition,
      adjacent genes show considerable heterogeneity in levels of gene expression, an
      observation that argues against chromatin-structure-mediated changes in gene
      expression levels. CONCLUSIONS: My results suggest that transcriptional
      inactivation of degenerating Y linked genes is an accidental by-product of
      mutation accumulation, and not driven by selection to either maintain expression
      at functional loci or downregulate maladapted genes from the neo-Y. Thus, most
      mutations observed on the neo-Y are likely to have deleterious effects on fitness
      and accumulate as a result of the reduced efficiency of natural selection on a
      nonrecombining chromosome, rather than neutrally or adaptively.

PMID- 16950106
TI  - Recruitment calling: a novel form of extended parental care in an altricial
      species.
AB  - In many altricial birds, fledglings disperse when they are no longer fed, and
      this dispersal marks the end of parental care. In some species, however, young
      remain in close association with their parents after nutritional independence.
      Because juveniles are still inferior foragers at this stage, they might benefit
      from parental assistance in locating good feeding sites, but this possibility
      remains largely unexplored. Here, we show that parents and helpers in pied
      babbler (Turdoides bicolor) societies use a recruitment call to direct
      nutritionally independent, but inexperienced, foragers to particular food
      patches. Observations and a playback experiment indicated that adult babblers use
      a "purr" call to recruit group members to a foraging patch. Creation of
      experimental foraging patches supported observations that individuals tend to
      give the call when they are foraging on abundant, divisible food sources and when
      their group contains independent fledglings (youngsters who are no longer fed
      directly). Fledglings responded to calls more often than adults, who frequently
      encountered aggression from the caller if they did, and the fledglings gained
      significant foraging benefits. This is the first study to demonstrate that
      altricial birds may use recruitment calls to extend parental care past the period
      of direct provisioning.

PMID- 16950107
TI  - Aurora B is enriched at merotelic attachment sites, where it regulates MCAK.
AB  - Kinetochores often form merotelic attachments, in which a single kinetochore is
      attached to microtubules from both spindle poles. These attachments can result in
      improper chromosome segregation and are a significant source of aneuploidy, a
      hallmark of cancer. Aurora B kinase and the kinesin-13 microtubule depolymerase
      mitotic-centromere-associated kinesin (MCAK) are required to release improper
      microtubule attachments. Aurora B regulates MCAK's activity and localization. We
      set out to understand why MCAK and Aurora B are more abundant at some metaphase
      aligned centromeres but are present at low amounts on most others. We found that
      members of the Aurora B complex are specifically enriched at merotelic attachment
      sites. We also found that Aurora B does not require its activity to become
      enriched at these sites; however, inhibition of Aurora B activity causes a
      significant increase in the number of merotelic attachments per cell. Aurora B
      activity enriches MCAK at merotelic attachments and phosphorylates MCAK on
      residues that regulate its microtubule depolymerase activity. These data
      demonstrate that proteins that resolve the defect are specifically localized to
      merotelic attachments, where their enzymatic activities are regulated.

PMID- 16950108
TI  - Aurora kinase promotes turnover of kinetochore microtubules to reduce chromosome
      segregation errors.
AB  - Merotelic kinetochore orientation is a misattachment in which a single
      kinetochore binds microtubules from both spindle poles rather than just one and
      can produce anaphase lagging chromosomes, a major source of aneuploidy. Merotelic
      kinetochore orientation occurs frequently in early mitosis, does not block
      chromosome alignment at the metaphase plate, and is not detected by the spindle
      checkpoint. However, microtubules to the incorrect pole are usually significantly
      reduced or eliminated before anaphase. We discovered that the frequency of
      lagging chromosomes in anaphase is very sensitive to partial inhibition of Aurora
      kinase activity by ZM447439 at a dose, 3 microM, that has little effect on
      histone phosphorylation, metaphase chromosome alignment, and cytokinesis in PtK1
      cells. Partial Aurora kinase inhibition increased the frequency of merotelic
      kinetochores in late metaphase, and the fraction of microtubules to the incorrect
      pole. Measurements of fluorescence dissipation after photoactivation showed that
      kinetochore-microtubule turnover in prometaphase is substantially suppressed by
      partial Aurora kinase inhibition. Our results support a preanaphase correction
      mechanism for merotelic attachments in which correct plus-end attachments are
      pulled away from high concentrations of Aurora B at the inner centromere, and
      incorrect merotelic attachments are destabilized by being pulled toward the inner
      centromere.

PMID- 16950109
TI  - Rab35 regulates an endocytic recycling pathway essential for the terminal steps
      of cytokinesis.
AB  - Cytokinesis is the final step of cell division and leads to the physical
      separation of the daughter cells. After the ingression of a cleavage membrane
      furrow that pinches the mother cell, future daughter cells spend much of the
      cytokinesis phase connected by an intercellular bridge. Rab proteins are major
      regulators of intracellular transport in eukaryotes, and here, we report an
      essential role for human Rab35 in both the stability of the bridge and its final
      abscission. We find that Rab35, whose function in membrane traffic was unknown,
      is localized to the plasma membrane and endocytic compartments and controls a
      fast endocytic recycling pathway. Consistent with a key requirement for Rab35
      regulated recycling during cell division, inhibition of Rab35 function leads to
      the accumulation of endocytic markers on numerous cytoplasmic vacuoles in cells
      that failed cytokinesis. Moreover, Rab35 is involved in the intercellular bridge
      localization of two molecules essential for the postfurrowing steps of
      cytokinesis: the phosphatidylinositol 4,5-bis phosphate (PIP2) lipid and the
      septin SEPT2. We propose that the Rab35-regulated pathway plays an essential role
      during the terminal steps of cytokinesis by controlling septin and PIP2
      subcellular distribution during cell division.

PMID- 16950110
TI  - Binocular coordination of the eyes during reading.
AB  - Saccadic eye movements and fixations are the behavioral means by which we
      visually sample text during reading. Human oculomotor control is governed by a
      complex neurophysiological system involving the brain stem, superior colliculus,
      and several cortical areas. A very widely held belief among researchers
      investigating primate vision is that the oculomotor system serves to orient the
      visual axes of both eyes to fixate the same target point in space. It is argued
      that such precise positioning of the eyes is necessary to place images on
      corresponding retinal locations, such that on each fixation a single,
      nondiplopic, visual representation is perceived. Vision works actively through a
      continual sampling process involving saccades and fixations. Here we report that
      during normal reading, the eyes do not always fixate the same letter within a
      word. We also demonstrate that saccadic targeting is yoked and based on a unified
      cyclopean percept of a whole word since it is unaffected if different word parts
      are delivered exclusively to each eye via a dichoptic presentation technique.
      These two findings together suggest that the visual signal from each eye is fused
      at a very early stage in the visual pathway, even when the fixation disparity is
      greater than one character (0.29 deg), and that saccade metrics for each eye are
      computed on the basis of that fused signal.

PMID- 16950111
TI  - Kisspeptin mediates the photoperiodic control of reproduction in hamsters.
AB  - The KiSS-1 gene encodes kisspeptin, the endogenous ligand of the G-protein
      coupled receptor GPR54. Recent data indicate that the KiSS-1/GPR54 system is
      critical for the regulation of reproduction and is required for puberty onset. In
      seasonal breeders, reproduction is tightly controlled by photoperiod (i.e., day
      length). The Syrian hamster is a seasonal model in which reproductive activity is
      promoted by long summer days (LD) and inhibited by short winter days (SD). Using
      in situ hybridization and immunohistochemistry, we show that KiSS-1 is expressed
      in the arcuate nucleus of LD hamsters. Importantly, the KiSS-1 mRNA level was
      lower in SD animals but not in SD-refractory animals, which spontaneously
      reactivated their sexual activity after several months in SD. These changes of
      expression are not secondary to the photoperiodic variations of gonadal steroids.
      In contrast, melatonin appears to be necessary for these seasonal changes because
      pineal-gland ablation prevented the SD-induced downregulation of KiSS-1
      expression. Remarkably, a chronic administration of kisspeptin-10 restored the
      testicular activity of SD hamsters despite persisting photoinhibitory conditions.
      Overall, these findings are consistent with a role of KiSS-1/GPR54 in the
      seasonal control of reproduction. We propose that photoperiod, via melatonin,
      modulates KiSS-1 signaling to drive the reproductive axis.

PMID- 16950112
TI  - Evolutionary psychology of spatial representations in the hominidae.
AB  - Comparatively little is known about the inherited primate background underlying
      human cognition, the human cognitive "wild-type." Yet it is possible to trace the
      evolution of human cognitive abilities and tendencies by contrasting the skills
      of our nearest cousins, not just chimpanzees, but all the extant great apes, thus
      showing what we are likely to have inherited from the common ancestor. By looking
      at human infants early in cognitive development, we can also obtain insights into
      native cognitive biases in our species. Here, we focus on spatial memory, a
      central cognitive domain. We show, first, that all nonhuman great apes and 1-year
      old human infants exhibit a preference for place over feature strategies for
      spatial memory. This suggests the common ancestor of all great apes had the same
      preference. We then examine 3-year-old human children and find that this
      preference reverses. Thus, the continuity between our species and the other great
      apes is masked early in human ontogeny. These findings, based on both
      phylogenetic and ontogenetic contrasts, open up the prospect of a systematic
      evolutionary psychology resting upon the cladistics of cognitive preferences.

PMID- 16950113
TI  - Light-induced activation of distinct modulatory neurons triggers appetitive or
      aversive learning in Drosophila larvae.
AB  - During classical conditioning, a positive or negative value is assigned to a
      previously neutral stimulus, thereby changing its significance for behavior. If
      an odor is associated with a negative stimulus, it can become repulsive.
      Conversely, an odor associated with a reward can become attractive. By using
      Drosophila larvae as a model system with minimal brain complexity, we address the
      question of which neurons attribute these values to odor stimuli. In insects,
      dopaminergic neurons are required for aversive learning, whereas octopaminergic
      neurons are necessary and sufficient for appetitive learning. However, it remains
      unclear whether two independent neuronal populations are sufficient to mediate
      such antagonistic values. We report the use of transgenically expressed
      channelrhodopsin-2, a light-activated cation channel, as a tool for
      optophysiological stimulation of genetically defined neuronal populations in
      Drosophila larvae. We demonstrate that distinct neuronal populations can be
      activated simply by illuminating the animals with blue light. Light-induced
      activation of dopaminergic neurons paired with an odor stimulus induces aversive
      memory formation, whereas activation of octopaminergic/tyraminergic neurons
      induces appetitive memory formation. These findings demonstrate that antagonistic
      modulatory subsystems are sufficient to substitute for aversive and appetitive
      reinforcement during classical conditioning.

PMID- 16950114
TI  - MEL-28, a novel nuclear-envelope and kinetochore protein essential for zygotic
      nuclear-envelope assembly in C. elegans.
AB  - The nuclear envelope (NE) of eukaryotic cells separates nucleoplasm from
      cytoplasm, mediates nucleo-cytoplasmic transport, and contributes to the control
      of gene expression. The NE consists of three major components: the nuclear
      membranes, the nuclear pore complexes (NPCs), and the nuclear lamina. The list of
      identified NE proteins has increased considerably during recent years but is most
      likely not complete. In most eukaryotes, the NE breaks down and is then
      reassembled during mitosis. The assembly of NPCs and the association and fusion
      of nuclear membranes around decondensing chromosomes are tightly coordinated
      processes. Here, we report the identification and characterization of MEL-28, a
      large protein essential for the assembly of a functional NE in C. elegans
      embryos. RNAi depletion or genetic mutation of mel-28 severely impairs nuclear
      morphology and leads to abnormal distribution of both integral NE proteins and
      NPCs. The structural defects of the NE were associated with functional defects
      and lack of nuclear exclusion of soluble proteins. MEL-28 localizes to NPCs
      during interphase, to kinetochores in early to middle mitosis then is widely
      distributed on chromatin late in mitosis. We show that MEL-28 is an early
      assembling, stable NE component required for all aspects of NE assembly.

PMID- 16950115
TI  - MEL-28 is downstream of the Ran cycle and is required for nuclear-envelope
      function and chromatin maintenance.
AB  - Early embryonic development depends on the faithful execution of basic cell
      biological processes whose coordination remains largely unknown. With a global
      network analysis, we found MEL-28 to be associated with two types of complexes,
      one implicated in nuclear-envelope function and the other in chromatin
      organization. Here, we show that MEL-28, a protein that shuttles between the
      nucleus and the kinetochore during the cell cycle, is required for the structural
      and functional integrity of the nuclear envelope. In addition, mel-28(RNAi)
      embryos exhibit defects in chromosome condensation, pronuclear migration,
      kinetochore assembly, and spindle assembly. This combination of mel-28(RNAi)
      phenotypes resemble those caused by depleting members of the Ran cycle in C.
      elegans, a conserved cellular signaling pathway that is required for mitotic
      spindle assembly, nuclear-envelope reformation after mitosis, and
      nucleocytoplasmic exchange (reviewed in). Although MEL-28 localization to the
      nuclear periphery is not dependent on nuclear pore components, it is dependent on
      RAN-1 and other key components of the Ran cycle. Thus, MEL-28 is downstream of
      the Ran cycle and is required for both proper nuclear-envelope function and
      chromatin maintenance.

PMID- 16950116
TI  - Mps1 phosphorylation by MAP kinase is required for kinetochore localization of
      spindle-checkpoint proteins.
AB  - The spindle checkpoint delays anaphase onset until all chromosomes have achieved
      bipolar attachment to the spindle microtubules. Unattached kinetochores activate
      the spindle checkpoint by recruiting several spindle-checkpoint proteins,
      including Mps1, Mad1, Mad2, Bub1, Bub3, and BubR1 (Mad3 in yeast). In vertebrate
      cells, active MAP kinase (MAPK) is also enriched at unattached kinetochores and
      is required for the spindle checkpoint. It has been shown that the kinase
      activity of Mps1 is required for the spindle checkpoint and for kinetochore
      localization of Bub1, Bub3, Mad1, and Mad2 . We herein demonstrate that MAPK
      phosphorylates Mps1 at S844 in Xenopus egg extracts. Interestingly, changing S844
      to unphosphorylatable alanine (S844A) has no effect on the kinase activity of
      Mps1, although it abolishes the checkpoint function of Mps1. Biochemical and
      immunofluorescence studies show that S844A mutation perturbs kinetochore
      localization of Mps1 and other spindle-checkpoint proteins, whereas the
      phosphorylation-mimicking S844D mutant restores their functions. Our studies
      suggest that Mps1 phosphorylation by MAPK at S844 might create a phosphoepitope
      that allows Mps1 to interact with kinetochores. In addition, our results indicate
      that active Mps1 must localize to kinetochores in order to execute its checkpoint
      function.

PMID- 16950117
TI  - Symmetry breaking in C. elegans: another gift from the sperm.
AB  - Polarization of the C. elegans embryo depends on the sperm-contributed
      centrosome, which cues a retraction of the actomyosin cortex to the opposite end
      of the embryo by an unknown mechanism. New evidence reveals that the sperm
      donates a second polarizing cue that may locally relax the actomyosin cortex near
      the point of sperm entry.

PMID- 16950118
TI  - Smad7: licensed to kill beta-catenin.
AB  - Elevated levels of inhibitory Smad7 are detected in several pathologic skin
      conditions; however the functional consequences of this expression have been
      unclear. A recent study shows that Smad7 overexpression in transgenic mouse
      epidermis at levels comparable to those seen in pathologic states is insufficient
      to block TGFbeta or BMP signaling, but instead produces striking phenotypes due
      to degradation of beta-catenin through a novel mechanism involving Smad7 and
      Smurf2.

PMID- 16950119
TI  - From pore to kinetochore and back: regulating envelope assembly.
AB  - Reassembly of the nuclear envelope following mitosis is a fundamental process
      that remains only partially understood. Two recent reports by and in the
      September 5 issue of Current Biology identify a novel protein, MEL-28, that
      shuttles between the nuclear pore complex and kinetochore and is essential for
      envelope assembly in C. elegans early embryos.

PMID- 16950120
TI  - Quantitative modeling in cell biology: what is it good for?
AB  - Recently, there has been a surge in the number of pioneering studies combining
      experiments with quantitative modeling to explain both relatively simple modules
      of molecular machinery of the cell and to achieve system-level understanding of
      cellular networks. Here we discuss the utility and methods of modeling and review
      several current models of cell signaling, cytoskeletal self-organization, nuclear
      transport, and the cell cycle. We discuss successes of and barriers to modeling
      in cell biology and its future directions, and we argue, using the field of
      bacterial chemotaxis as an example, that the closer the complete systematic
      understanding of cell behavior is, the more important modeling becomes and the
      more experiment and theory merge.

PMID- 16950121
TI  - Quantitative models of developmental pattern formation.
AB  - Pattern formation in developing organisms can be regulated at a variety of
      levels, from gene sequence to anatomy. At this level of complexity, mechanistic
      models of development become essential for integrating data, guiding future
      experiments, and predicting the effects of genetic and physical perturbations.
      However, the formulation and analysis of quantitative models of development are
      limited by high levels of uncertainty in experimental measurements, a large
      number of both known and unknown system components, and the multiscale nature of
      development. At the same time, an expanding arsenal of experimental tools can
      constrain models and directly test their predictions, making the modeling efforts
      not only necessary, but feasible. Using a number of problems in fruit fly
      development, we discuss how models can be used to test the feasibility of
      proposed patterning mechanisms and characterize their systems-level properties.

PMID- 16950122
TI  - Smad7-induced beta-catenin degradation alters epidermal appendage development.
AB  - To assess whether Smad signaling affects skin development, we generated
      transgenic mice in which a Smad antagonist, Smad7, was induced in keratinocytes,
      including epidermal stem cells. Smad7 transgene induction perturbed hair follicle
      morphogenesis and differentiation, but accelerated sebaceous gland morphogenesis.
      Further analysis revealed that independent of its role in anti-Smad signaling,
      Smad7 bound beta-catenin and induced beta-catenin degradation by recruiting an E3
      ligase, Smurf2, to the Smad7/beta-catenin complex. Consequently, Wnt/beta-catenin
      signaling was suppressed in Smad7 transgenic hair follicles. Coexpression of the
      Smurf2 and Smad7 transgenes exacerbated Smad7-induced abnormalities in hair
      follicles and sebaceous glands. Conversely, when endogenous Smad7 was knocked
      down, keratinocytes exhibited increased beta-catenin protein and enhanced Wnt
      signaling. Our data reveal a mechanism for Smad7 in antagonizing Wnt/beta-catenin
      signaling, thereby shifting the skin differentiation program from forming hair
      follicles to sebaceous glands.

PMID- 16950123
TI  - The nodal precursor acting via activin receptors induces mesoderm by maintaining
      a source of its convertases and BMP4.
AB  - During early mouse development, the subtilisin-like proprotein convertases (SPC)
      Furin and PACE4 pattern the primitive ectoderm and visceral endoderm, presumably
      by activating the TGFss-related Nodal precursor. Here, mutation of the SPC motif
      provides direct evidence that Nodal processing is essential to specify anterior
      visceral endoderm and mesendoderm. Surprisingly, however, the Nodal precursor
      binds and activates activin receptors to maintain expression of Furin, PACE4, and
      Bmp4 in extraembryonic ectoderm at a distance from the Nodal source. In return,
      Bmp4 induces Wnt3, which amplifies Nodal expression in the epiblast and mediates
      induction of mesoderm. We conclude that uncleaved Nodal sustains the
      extraembryonic source of proprotein convertases and Bmp4 to amplify Nodal
      signaling in two nonredundant feedback loops with dual timescales and to localize
      primitive streak formation at the posterior pole. Based on mathematical modeling,
      we discuss how these sequential loops control cell fate.

PMID- 16950124
TI  - Wnt signaling inhibitors regulate the transcriptional response to morphogenetic
      Shh-Gli signaling in the neural tube.
AB  - Shh-Gli signaling controls cell fates in the developing ventral neural tube by
      regulating the patterned expression of transcription factors in neural
      progenitors. However, the molecular mechanisms that limit target gene responses
      to specific domains are unclear. Here, we show that Wnt pathway inhibitors
      regulate the threshold response of a ventral Shh target gene, Nkx2.2, to
      establish its restricted expression in the ventral spinal cord. Identification
      and characterization of an Nkx2.2 enhancer reveals that expression is directly
      regulated by positive Shh-Gli signaling and negative Tcf repressor activity. Our
      data indicate that the dorsal limit of Nkx2.2 is controlled by Tcf4-mediated
      transcriptional repression, and not by a direct requirement for high-level Shh
      Gli signaling, arguing against a simple model based on differential Gli factor
      affinities in target genes. These results identify a transcriptional mechanism
      that integrates graded Shh and Wnt signaling to define progenitor gene expression
      domains and cell fates in the neural tube.

PMID- 16950125
TI  - An FGF response pathway that mediates hepatic gene induction in embryonic
      endoderm cells.
AB  - While particular combinations of mesodermal signals are known to induce distinct
      tissue-specific programs in the endoderm, there is little information about the
      response pathways within endoderm cells that control their specification. We have
      used signaling inhibitors on embryo tissue explants and whole-embryo cultures as
      well as genetic approaches to reveal part of an intracellular network by which
      FGF signaling helps induce hepatic genes and stabilize nascent hepatic cells
      within the endodermal epithelium. Specifically, we found that hepatic gene
      induction is elicited by an FGF/MAPK pathway. Although the PI3K pathway is
      activated in foregut endoderm cells, its inhibition does not block hepatic gene
      induction in explants; however, it does block tissue growth. We also found that
      at the onset of hepatogenesis, the FGF/MAPK and PI3K pathways do not
      crossregulate in the endoderm. The finding of separate pathways for endoderm
      tissue specification and growth provides insights for guiding cellular
      regeneration and stem cell differentiation.

PMID- 16950126
TI  - Syk and Slp-76 mutant mice reveal a cell-autonomous hematopoietic cell
      contribution to vascular development.
AB  - Developmental studies support a common origin for blood and endothelial cells,
      while studies of adult angiogenic responses suggest that the hematopoietic system
      can be a source of endothelial cells later in life. Whether hematopoietic tissue
      is a source of endothelial cells during normal vascular development is unknown.
      Mouse embryos lacking the signaling proteins Syk and Slp-76 develop abnormal
      blood-lymphatic endothelial connections. Here we demonstrate that expression of
      GFPSlp-76 in a subset of hematopoietic cells rescues this phenotype, and that
      deficient cells confer focal vascular phenotypes in chimeric embryos consistent
      with a cell-autonomous mechanism. Endogenous Syk and Slp-76, as well as
      transgenic GFPSlp-76, are expressed in circulating cells previously proposed to
      be endothelial precursors, supporting a causal role for these cells. These
      studies provide genetic evidence for hematopoietic contribution to vascular
      development and suggest that hematopoietic tissue can provide a source of
      vascular endothelial progenitor cells throughout life.

PMID- 16950127
TI  - The FERM protein Yurt is a negative regulatory component of the Crumbs complex
      that controls epithelial polarity and apical membrane size.
AB  - The Crumbs (Crb) complex is a key regulator of epithelial cell architecture where
      it promotes apical membrane formation. Here, we show that binding of the FERM
      protein Yurt to the cytoplasmic domain of Crb is part of a negative-feedback loop
      that regulates Crb activity. Yurt is predominantly a basolateral protein but is
      recruited by Crb to apical membranes late during epithelial development. Loss of
      Yurt causes an expansion of the apical membrane in embryonic epithelia and
      photoreceptor cells similar to Crb overexpression and in contrast to loss of Crb.
      Analysis of yurt crb double mutants suggests that these genes function in one
      pathway and that yurt negatively regulates crb. We also show that the mammalian
      Yurt orthologs YMO1 and EHM2 bind to mammalian Crb proteins. We propose that Yurt
      is part of an evolutionary conserved negative-feedback mechanism that restricts
      Crb complex activity in promoting apical membrane formation.

PMID- 16950128
TI  - Cytoplasmic gamma-actin is not required for skeletal muscle development but its
      absence leads to a progressive myopathy.
AB  - Nonmuscle gamma(cyto)-actin is expressed at very low levels in skeletal muscle
      but uniquely localizes to costameres, the cytoskeletal networks that couple
      peripheral myofibrils to the sarcolemma. We generated and analyzed skeletal
      muscle-specific gamma(cyto)-actin knockout (Actg1-msKO) mice. Although muscle
      development proceeded normally, Actg1-msKO mice presented with overt muscle
      weakness accompanied by a progressive pattern of muscle fiber
      necrosis/regeneration. Functional deficits in whole-body tension and isometric
      twitch force were observed, consistent with defects in the connectivity between
      muscle fibers and/or myofibrils or at the myotendinous junctions. Surprisingly,
      gamma(cyto)-actin-deficient muscle did not demonstrate the fibrosis,
      inflammation, and membrane damage typical of several muscular dystrophies but
      rather presented with a novel progressive myopathy. Together, our data
      demonstrate an important role for minimally abundant but strategically localized
      gamma(cyto)-actin in adult skeletal muscle and describe a new mouse model to
      study the in vivo relevance of subcellular actin isoform sorting.

PMID- 16950129
TI  - Actin homolog MreBH governs cell morphogenesis by localization of the cell wall
      hydrolase LytE.
AB  - MreB proteins are bacterial actin homologs involved in cell morphogenesis and
      various other cellular processes. However, the effector proteins used by MreBs
      remain largely unknown. Bacillus subtilis has three MreB isoforms. Mbl and
      possibly MreB have previously been shown to be implicated in cell wall synthesis.
      We have now found that the third isoform, MreBH, colocalizes with the two other
      MreB isoforms in B. subtilis and also has an important role in cell
      morphogenesis. MreBH can physically interact with a cell wall hydrolase, LytE,
      and is required for its helical pattern of extracellular localization. Moreover,
      lytE and mreBH mutants exhibit similar cell-wall-related defects. We propose that
      controlled elongation of rod-shaped B. subtilis depends on the coordination of
      cell wall synthesis and hydrolysis in helical tracts defined by MreB proteins.
      Our data also suggest that physical interactions with intracellular actin bundles
      can influence the later localization pattern of extracellular effectors.

PMID- 16950130
TI  - GTP hydrolysis by the Rho family GTPase TC10 promotes exocytic vesicle fusion.
AB  - TC10, a Rho family GTPase, has been shown to play an important role in the
      exocytosis of GLUT4 and other proteins, primarily by tethering the vesicles at
      the plasma membrane. Using a newly developed probe based on fluorescence
      resonance energy transfer, we found that TC10 activity at tethered vesicles
      dropped immediately before vesicle fusion in HeLa cells stimulated with epidermal
      growth factor (EGF), suggesting that GTP hydrolysis by TC10 is a critical step in
      vesicle fusion. In support of this model, a GTPase-deficient TC10 mutant potently
      inhibited EGF-induced vesicular fusion in HeLa cells and depolarization-induced
      neuronal secretion. Furthermore, we found that GTP hydrolysis by TC10 in the
      vicinity of the plasma membrane was dependent on Rac and the redox-regulated Rho
      GAP, p190RhoGAP-A. We propose that an EGF-stimulated GAP accelerates GTP
      hydrolysis of TC10, thereby promoting vesicle fusion.

PMID- 16950131
TI  - Phospho-regulation of the Cdc14/Clp1 phosphatase delays late mitotic events in S.
      pombe.
AB  - In eukaryotes, exit from mitosis occurs through the inactivation of the Cdk1
      cyclin B kinase complex and the reversal of its phosphorylation events. These
      late mitotic events are tightly regulated to occur only after the onset of
      anaphase and prior to cytokinesis. Central to this regulation is the conserved
      Cdc14 family of protein phosphatases, whose activity reverses Cdk-dependent
      phosphorylation events. S. cerevisiae Cdc14 activity is restrained from
      dephosphorylating Cdk substrates and inactivating Cdk1 through its nucleolar
      sequestration prior to anaphase. Here, we describe a unique mode of Cdc14
      regulation that operates prior to anaphase in fission yeast. Cdk1 phosphorylates
      and inhibits the catalytic activity of the Cdc14 family member, Clp1/Flp1. As
      Cdk1 activity declines during anaphase progression, Clp1/Flp1 autocatalytically
      reverses these phosphorylation events to stimulate its own activity. These
      findings point to a simple regulatory circuit that couples Cdk1 activation with
      its inactivation mediated through phosphorylation-dependent regulation of
      Clp1/Flp1 phosphatase activity.

PMID- 16950132
TI  - Insulin biosynthesis: the IREny of it all.
AB  - Recent studies have shown that the unfolded protein response (UPR) is essential
      for the survival of insulin-producing beta cells. Work in this issue of Cell
      Metabolism (Lipson et al., 2006) identifies a novel role for UPR activation in
      beta cell function by demonstrating that the UPR effector IRE1 is a positive
      regulator of glucose-stimulated proinsulin biosynthesis.

PMID- 16950133
TI  - Xenobiotic receptor meets NF-kappaB, a collision in the small bowel.
AB  - It has long been appreciated that inflammation and infection reduce drug
      metabolism and that exposure to drug metabolism-inducing xenobiotics can impair
      immune function. A new study reveals the mutual repression between the xenobiotic
      nuclear receptor PXR/SXR and NF-kappaB signaling pathways, providing a molecular
      mechanism linking xenobiotic metabolism and inflammation (Zhou et al.,).

PMID- 16950134
TI  - Is the slippery slope from steatosis to steatohepatitis paved with triglyceride
      or cholesterol?
AB  - Accumulation of hepatic lipids has been thought to trigger the inflammation,
      apoptosis, and fibrosis that characterize progression of hepatic steatosis to
      steatohepatitis and cirrhosis. In this issue of Cell Metabolism, Mari et al.
      (2006) provide evidence for excessive mitochondrial free cholesterol as a cause
      of the progession of steatosis to more severe liver disease.

PMID- 16950135
TI  - An ARC light on lipid metabolism.
AB  - The SREBP pathway plays a central role in the regulation of lipid metabolism. In
      a recent letter, Yang et al. present a comprehensive series of experiments,
      spanning a wide range of disciplines, that identify ARC105 as a component of the
      ARC complex that interacts directly with SREBP and is necessary for SREBP
      function (Yang et al., 2006).

PMID- 16950136
TI  - Mitochondrial free cholesterol loading sensitizes to TNF- and Fas-mediated
      steatohepatitis.
AB  - The etiology of progression from steatosis to steatohepatitis (SH) remains
      unknown. Using nutritional and genetic models of hepatic steatosis, we show that
      free cholesterol (FC) loading, but not free fatty acids or triglycerides,
      sensitizes to TNF- and Fas-induced SH. FC distribution in endoplasmic reticulum
      (ER) and plasma membrane did not cause ER stress or alter TNF signaling. Rather,
      mitochondrial FC loading accounted for the hepatocellular sensitivity to TNF due
      to mitochondrial glutathione (mGSH) depletion. Selective mGSH depletion in
      primary hepatocytes recapitulated the susceptibility to TNF and Fas seen in FC
      loaded hepatocytes; its repletion rescued FC-loaded livers from TNF-mediated SH.
      Moreover, hepatocytes from mice lacking NPC1, a late endosomal cholesterol
      trafficking protein, or from obese ob/ob mice, exhibited mitochondrial FC
      accumulation, mGSH depletion, and susceptibility to TNF. Thus, we propose a
      critical role for mitochondrial FC loading in precipitating SH, by sensitizing
      hepatocytes to TNF and Fas through mGSH depletion.

PMID- 16950137
TI  - Lipin 1 is an inducible amplifier of the hepatic PGC-1alpha/PPARalpha regulatory
      pathway.
AB  - Perturbations in hepatic lipid homeostasis are linked to the development of
      obesity-related steatohepatitis. Mutations in the gene encoding lipin 1 cause
      hepatic steatosis in fld mice, a genetic model of lipodystrophy. However, the
      molecular function of lipin 1 is unclear. Herein, we demonstrate that the
      expression of lipin 1 is induced by peroxisome proliferator-activated receptor
      gamma (PPARgamma) coactivator 1alpha (PGC-1alpha), a transcriptional coactivator
      controlling several key hepatic metabolic pathways. Gain-of-function and loss-of
      function strategies demonstrated that lipin selectively activates a subset of PGC
      1alpha target pathways, including fatty acid oxidation and mitochondrial
      oxidative phosphorylation, while suppressing the lipogenic program and lowering
      circulating lipid levels. Lipin activates mitochondrial fatty acid oxidative
      metabolism by inducing expression of the nuclear receptor PPARalpha, a known PGC
      1alpha target, and via direct physical interactions with PPARalpha and PGC
      1alpha. These results identify lipin 1 as a selective physiological amplifier of
      the PGC-1alpha/PPARalpha-mediated control of hepatic lipid metabolism.

PMID- 16950138
TI  - A CD36-dependent signaling cascade is necessary for macrophage foam cell
      formation.
AB  - Accumulation of macrophage foam cells in atherosclerotic blood vessel intima is a
      critical component of atherogenesis mediated by scavenger receptor-dependent
      internalization of oxidized LDL. We demonstrated by coimmunoprecipitation and
      pull-down assays that the macrophage scavenger receptor CD36 associates with a
      signaling complex containing Lyn and MEKK2. The MAP kinases JNK1 and JNK2 were
      specifically phosphorylated in macrophages exposed to oxLDL. Using cells isolated
      from SRA, TLR2, or CD36 null mice, and phospholipid ligands specific for either
      SRA or CD36, we showed that JNK activation was mediated by CD36. Both foam cell
      formation and activation of JNK2 in hyperlipidemic mice were diminished in the
      absence of CD36. Furthermore, inhibition of Src or JNK blocked oxLDL uptake and
      inhibited foam cell formation in vitro and in vivo. These findings show that a
      specific CD36-dependent signaling pathway initiated by oxLDL is necessary for
      foam cell formation and identify potential targets for antiatherosclerosis
      therapy.

PMID- 16950139
TI  - Critical role for peptide YY in protein-mediated satiation and body-weight
      regulation.
AB  - Dietary protein enhances satiety and promotes weight loss, but the mechanisms by
      which appetite is affected remain unclear. We investigated the role of gut
      hormones, key regulators of ingestive behavior, in mediating the satiating
      effects of different macronutrients. In normal-weight and obese human subjects,
      high-protein intake induced the greatest release of the anorectic hormone peptide
      YY (PYY) and the most pronounced satiety. Long-term augmentation of dietary
      protein in mice increased plasma PYY levels, decreased food intake, and reduced
      adiposity. To directly determine the role of PYY in mediating the satiating
      effects of protein, we generated Pyy null mice, which were selectively resistant
      to the satiating and weight-reducing effects of protein and developed marked
      obesity that was reversed by exogenous PYY treatment. Our findings suggest that
      modulating the release of endogenous satiety factors, such as PYY, through
      alteration of specific diet constituents could provide a rational therapy for
      obesity.

PMID- 16950140
TI  - Ctr1 drives intestinal copper absorption and is essential for growth, iron
      metabolism, and neonatal cardiac function.
AB  - The trace element copper (Cu) is a cofactor for biochemical functions ranging
      from energy generation to iron (Fe) acquisition, angiogenesis, and free radical
      detoxification. While Cu is essential for life, the molecules that mediate
      dietary Cu uptake have not been identified. Ctr1 is a homotrimeric protein,
      conserved from yeast to humans, that transports Cu across the plasma membrane
      with high affinity and specificity. Here we describe the generation of intestinal
      epithelial cell-specific Ctr1 knockout mice. These mice exhibit striking neonatal
      defects in Cu accumulation in peripheral tissues, hepatic Fe overload, cardiac
      hypertrophy, and severe growth and viability defects. Consistent with an
      intestinal Cu absorption block, the growth and viability defects can be partially
      rescued by a single postnatal Cu administration, indicative of a critical
      neonatal metabolic requirement for Cu that is provided by intestinal Ctr1. These
      studies identify Ctr1 as the major factor driving intestinal Cu absorption in
      mammals.

PMID- 16950143
TI  - Single-photon emission computed tomography/computed tomography: basic
      instrumentation and innovations.
AB  - Correlation of the anatomical and functional information presented by single
      photon emission computed tomography (SPECT) and computed tomography (CT) can aid
      in the decision-making process by enabling better localization and definition of
      organs and lesions and improving the precision of surgical biopsies. Technical
      developments over the past 20 years have led to the development of better
      software techniques for image fusion and, more recently, to the development of
      modern SPECT/CT systems. While image fusion techniques have been in clinical use
      for many years, the first commercial SPECT/CT system was only developed in 1999.
      Following the commercial success of PET/CT systems that employed multidetector CT
      (MDCT) scanners, there has been renewed interest in the development of comparable
      SPECT/CT systems. This has resulted in the development of a range of SPECT/CT
      devices varying from a simple CT add-on to a conventional SPECT system that can
      provide low-dose CT images to a full MDCT scanner integrated with a SPECT system.
      The advantages of combining SPECT with CT are numerous and are primarily due to
      the anatomic referencing and the attenuation correction capabilities of CT.
      Depending on system design, there are varying technical issues surrounding the
      different SPECT/CT devices, ranging from cost, radiation dose, planning, and
      siting requirements to system-specific issues such as table sag and CT artifacts
      due to patient motion. Motion artifacts should be less prevalent with the faster
      acquisition times of modern scanners, but are still problematic in the thorax and
      have not yet been fully resolved as they pertain to the use of CT data for
      cardiac attenuation correction. As this technology matures, we can expect to see
      a range of SPECT/CT devices available on the market that range from low-dose 1-4
      slice inexpensive CT upgrades of conventional SPECT systems, to SPECT systems
      incorporating 64 or 128 slices CT scanners. The cost of the high-end CT scanners
      will exceed the cost of the SPECT scanner and hence the justification for such
      devices will be heavily dependent on clear demonstration of their value in
      clinical practice.

PMID- 16950141
TI  - Regulation of insulin biosynthesis in pancreatic beta cells by an endoplasmic
      reticulum-resident protein kinase IRE1.
AB  - In pancreatic beta cells, the endoplasmic reticulum (ER) is an important site for
      insulin biosynthesis and the folding of newly synthesized proinsulin. Here, we
      show that IRE1alpha, an ER-resident protein kinase, has a crucial function in
      insulin biosynthesis. IRE1alpha phosphorylation is coupled to insulin
      biosynthesis in response to transient exposure to high glucose; inactivation of
      IRE1alpha signaling by siRNA or inhibition of IRE1alpha phosphorylation hinders
      insulin biosynthesis. IRE1 activation by high glucose does not accompany XBP-1
      splicing and BiP dissociation but upregulates its target genes such as WFS1.
      Thus, IRE1 signaling activated by transient exposure to high glucose uses a
      unique subset of downstream components and has a beneficial effect on pancreatic
      beta cells. In contrast, chronic exposure of beta cells to high glucose causes ER
      stress and hyperactivation of IRE1, leading to the suppression of insulin gene
      expression. IRE1 signaling is therefore a potential target for therapeutic
      regulation of insulin biosynthesis.

PMID- 16950144
TI  - Single-photon emission computed tomography/computed tomography in endocrinology.
AB  - The introduction of fusion of functional and anatomical imaging modalities into
      the field of endocrinology led to a major breakthrough in diagnosis, staging, and
      follow-up of patients with endocrine tumors. The management of endocrine tumors
      is based on a wide variety of conventional techniques, including computed
      tomography, ultrasound, or magnetic resonance imaging, and on scintigraphic
      functional techniques, associated with unique uptake and transport mechanisms and
      with the presence of high density of membrane receptors on some of these tumors.
      Anatomical modalities provide accurate detection and localization of
      morphological abnormalities, whereas nuclear medicine studies reflect the
      pathophysiological status of the disease process. Lack of structural delineation
      and relatively low contrast hamper the precise anatomical localization of the
      abnormal functional findings in the presence of potential concurrent foci related
      to the physiological biodistribution of the radiotracer or to processes unrelated
      to the evaluated disease entity. The notion that anatomical high-resolution and
      functional imaging data act as complementary methods led to various combination
      techniques of these modalities. However, coregistration of the functional and
      anatomical data after the acquisition of the 2 imaging modalities on separate
      machines, in different sessions, fails to provide accurate alignment of data, and
      the mathematical modeling is too cumbersome to be used on a routine basis. In
      contrast, hybrid imaging devices of single-photon emission computed
      tomography/computed tomography in a single gantry enable the sequential
      acquisition of the two modalities, with subsequent merging of data into a
      composite image display. These hybrid studies have led to a revolution in the
      field of imaging, providing clinically relevant information that is not apparent
      on separate images. The present review evaluates the contribution of the
      integrated single-photon emission computed tomography/computed tomography
      technology to image analysis and management of patients with endocrine tumors.

PMID- 16950145
TI  - Single-photon emission computed tomography/computed tomography in lung cancer and
      malignant lymphoma.
AB  - In nuclear oncology, despite the fast-growing diffusion of (18)F
      fluorodeoxyglucose positron emission tomography (FDG-PET), single-photon emission
      computed tomography (SPECT) studies can still play an useful clinical role in
      several applications. The main limitation of SPECT imaging with tumor-seeking
      agents is the lack of the structural delineation of the pathologic processes they
      detect; this drawback sometimes renders SPECT interpretation difficult and can
      diminish its diagnostic accuracy. Fusion with morphological studies can overcome
      this limitation by giving an anatomical map to scintigraphic data. In the past,
      software-based fusion of independently performed SPECT and CT images proved to be
      time-consuming and impractical for routine use. The recent development of dual
      modality integrated imaging systems that provide functional (SPECT) and
      anatomical (CT) images in the same scanning session, with the acquired images
      coregistered by means of the hardware, has opened a new era in this field. The
      first reports indicate that SPECT/CT is very useful in cancer imaging because it
      is able to provide further information of clinical value in several cases. In
      SPECT, studies of lung cancer and malignant lymphomas using different
      radiopharmaceutical, hybrid images are of value in providing the correct
      localization of tumor sites, with a precise detection of the involved organs, and
      the definition of their functional status, and in allowing the exclusion of
      disease in sites of physiologic tracer uptake. Therefore, in lung cancer and
      lymphomas, hybrid SPECT/CT can play a role in the diagnosis of the primary tumor,
      in the staging of the disease, in the follow-up, in the monitoring of therapy, in
      the detection of recurrence, and in dosimetric estimations for target
      radionuclide therapy.

PMID- 16950146
TI  - The role of single-photon emission computed tomography/computed tomography in
      benign and malignant bone disease.
AB  - Radiological (plain radiographs, computed tomography [CT], magnetic resonance
      imaging [MRI]) and nuclear medicine methods (bone scan, leukocyte scan) both
      provide unique information about the status of the skeleton. Both have typical
      strengths and weaknesses, which often lead to the sequential use of different
      procedures in daily routine. This use causes the unnecessary loss of time and
      sometimes money, if redundant information is obtained without establishing a
      final diagnosis. Recently, new devices for hybrid imaging (single-photon emission
      computed tomography/computed tomography [SPECT/CT], positron emission
      tomography/computed tomography [PET/CT]) were introduced, which allow for direct
      fusion of morphological (CT) and functional (SPECT, PET) data sets. With regard
      to skeletal abnormalities, this approach appears to be extremely useful because
      it combines the advantages of both techniques (high-resolution imaging of bone
      morphology and high sensitivity imaging of bone metabolism). By the accurate
      correlation of both, a new quality of bone imaging has now become accessible.
      Although researchers undertaking the initial studies exclusively used low-dose CT
      equipment, a new generation of SPECT/CT devices has emerged recently. By
      integrating high-resolution spiral CT, quality of bone imaging may improve once
      more. Ongoing prospective studies will have to show whether completely new
      diagnostic algorithms will come up for classification of bone disease as a
      consequence of this development. Besides, the role of ultrasonography and MRI for
      bone and soft-tissue imaging also will have to be re-evaluated. Looking at the
      final aim of all imaging techniques--to achieve correct diagnosis in a fast,
      noninvasive, comprehensive, and inexpensive way--we are now on the edge of a new
      era of multimodality imaging that will probably change the paths and structure of
      medicine in many ways. Presently, hybrid imaging using SPECT/CT has been proven
      to increase sensitivity and specificity of bone scintigraphy. This was mainly
      achieved by identifying benign bone conditions with increased bone turnover.
      Therefore, SPECT/CT should be applied whenever equivocal findings of planar bone
      imaging occur. It also helps to improve accuracy of leukocyte scanning to
      detect/exclude osteomyelitis and to define sites of inflammation. We therefore
      regard SPECT/CT as a valuable tool to optimize bone imaging, which might become
      even more important if new radiopharmaceuticals become available to image
      specific cell functions.

PMID- 16950147
TI  - Optimized scintigraphic evaluation of infection and inflammation: role of single
      photon emission computed tomography/computed tomography fusion imaging.
AB  - Gallium-67 citrate and radiolabeled white blood cells have become standard
      inflammation/infection-seeking agents whereas other agents, such as (99m)Tc
      diphosphonates, commonly are used to infer an infectious process. These
      radiopharmaceuticals reflect physiologic and pathologic function rather than
      anatomical abnormality. In the clinical setting, it is often necessary to
      correlate these functional studies with anatomical imaging. The advent of single
      photon emission computed tomography, as well as positron emission tomography,
      provides tomographic images for direct correlation to anatomic modalities such as
      computed tomography and magnetic resonance imaging. The methods by which these
      functional and anatomic imaging modalities are correlated include side-by-side,
      software, and hardware fusion. Clinically, fusion imaging has been applied
      primarily to oncologic and neurologic applications. The literature supports the
      premise that multimodality fusion would increase the specificity of the
      physiologic modality and increase the sensitivity of the anatomic modality. Our
      institution uses software fusion to aid in the diagnosis of infection and
      inflammation. Through case vignettes, we illustrate applications for single
      photon emission computed tomography/computed tomography fusion for the diagnosis
      of infection and inflammation in multiple organ systems.

PMID- 16950148
TI  - Association of intersection approach speed with driver characteristics, vehicle
      type and traffic conditions comparing urban and suburban areas.
AB  - A mobile recording system, with integrated laser speed gun, video from CCD
      cameras and auxiliary battery system, was used to observe driving behavior at an
      urban intersection and a suburban analog. After removal of instances of
      interference, 1538 driving behaviors were recorded. Multiple regression was then
      utilized to examine the factors affecting approaching speed. Speed limit
      violation was considered a dichotomous variable with two categories, violation
      and compliance. Binary logistic regression was also used to examine the risk of
      speeding as a function of covariates and interaction terms. The results of
      analysis revealed that the major contributing factors for approaching speed were
      site, rush-hour-status, traffic light condition, vehicle type and driver gender.
      In particular, light status was the highest contributor to speed. In addition,
      the results of logistic regression showed significant sites and rush-hour effects
      on speeding, with the risk of limit violation in the suburbs nearly six-fold that
      in urban areas. The relative risk of speeding for travelling in non-rush hours is
      three times higher than that for rush-hour. In terms of driver characteristics,
      male drivers under 55 years of age had the greatest speeding propensity in our
      sample. The results of the present study may provide meaningful information
      applicable to the design and operation of signalized intersections.

PMID- 16950149
TI  - The utility of a workplace injury instrument in prediction of workplace injury.
AB  - Workplace injuries are common and destructive to persons, organisations, and
      society. Various instruments presently exist that are designed to assess the
      factors underlying workplace injury. The study reports on the construct and
      predictive validity of a 46-item instrument, the safety perception survey (SPS),
      currently used to assess safety climate in industrial organisations throughout
      Australia. Initially, factor analysis was conducted on the data from a sample of
      1238 employees from nine organisations, which indicated a one-factor solution,
      was the best fit. A structural equation model (SEM) linking injury rates to the
      safety climate measure for 16 sub-groups of six industrial organisations
      indicated that the measure contributed just 23% of the variance in injury rates.
      Interestingly, the results indicated that the number of employees was a better
      and more significant predictor of injury (R(2)=0.48). It is proposed that the SPS
      as is would need to be modified significantly from its current form to produce
      improvements in validity, as in its current form the survey is no more predictive
      of injury than organisational size. Future research into safety climate measures
      should incorporate predictive validity analysis on injury rates, as for many
      organisations; this is a performance outcome measure.

PMID- 16950150
TI  - Synaptic vesicles: half full or half empty?
AB  - The regulation of quantal size through pre- rather than postsynaptic mechanisms
      has recently received considerable attention as a potential mechanism for
      plasticity. Vesicular transporters catalyze the filling of synaptic vesicles with
      transmitter and are thus potential substrates for such presynaptic regulation. In
      this issue of Neuron, Prado et al. pursue this line of investigation and show
      that changes in transporter expression that alter quantal size can affect
      behavior.

PMID- 16950151
TI  - Subplate neurons foster inhibition.
AB  - Previous work demonstrates an essential role of subplate neurons during ocular
      dominance (OD) column formation in the developing visual cortex. While inhibitory
      circuitry has also been shown to play an essential role in OD plasticity, the
      relationship between subplate neurons and the development of inhibitory circuits
      has been unclear. In this issue of Neuron, Kanold and Shatz provide evidence that
      maturation of inhibitory circuitry requires subplate neurons in the developing
      cortex.

PMID- 16950152
TI  - Principles of diffusion tensor imaging and its applications to basic neuroscience
      research.
AB  - The brain contains more than 100 billion neurons that communicate with each other
      via axons for the formation of complex neural networks. The structural mapping of
      such networks during health and disease states is essential for understanding
      brain function. However, our understanding of brain structural connectivity is
      surprisingly limited, due in part to the lack of noninvasive methodologies to
      study axonal anatomy. Diffusion tensor imaging (DTI) is a recently developed MRI
      technique that can measure macroscopic axonal organization in nervous system
      tissues. In this article, the principles of DTI methodologies are explained, and
      several applications introduced, including visualization of axonal tracts in
      myelin and axonal injuries as well as human brain and mouse embryonic
      development. The strengths and limitations of DTI and key areas for future
      research and development are also discussed.

PMID- 16950153
TI  - Dopamine scales performance in the absence of new learning.
AB  - Learning and motivation are integral in shaping an organism's adaptive behavior.
      The dopamine system has been implicated in both processes; however, dissociating
      the two, both experimentally and conceptually, has posed significant challenges.
      We have developed an animal model that dissociates expression or scaling of a
      learned behavior from learning itself. An inducible dopamine transporter (DAT)
      knockdown mouse line has been generated, which exhibits significantly slower
      reuptake of released dopamine and increased tonic firing of dopamine neurons
      without altering phasic burst firing. Mice were trained in experimental tasks
      prior to inducing a hyperdopaminergic tone and then retested. Elevated dopamine
      enhanced performance in goal-directed operant responses. These data demonstrate
      that alterations in dopaminergic tone can scale the performance of a previously
      learned behavior in the absence of new learning.

PMID- 16950154
TI  - A genomic screen for modifiers of tauopathy identifies puromycin-sensitive
      aminopeptidase as an inhibitor of tau-induced neurodegeneration.
AB  - Neurofibrillary tangles (NFT) containing tau are a hallmark of neurodegenerative
      diseases, including Alzheimer's disease (AD). NFT burden correlates with
      cognitive decline and neurodegeneration in AD. However, little is known about
      mechanisms that protect against tau-induced neurodegeneration. We used a cross
      species functional genomic approach to analyze gene expression in multiple brain
      regions in mouse, in parallel with validation in Drosophila, to identify tau
      modifiers, including the highly conserved protein puromycin-sensitive
      aminopeptidase (PSA/Npepps). PSA protected against tau-induced neurodegeneration
      in vivo, whereas PSA loss of function exacerbated neurodegeneration. We further
      show that human PSA directly proteolyzes tau in vitro. These data highlight the
      utility of using both evolutionarily distant species for genetic screening and
      functional assessment to identify modifiers of neurodegeneration. Further
      investigation is warranted in defining the role of PSA and other genes identified
      here as potential therapeutic targets in tauopathy.

PMID- 16950155
TI  - GIRK channel activation involves a local rearrangement of a preformed G protein
      channel complex.
AB  - G protein-coupled signaling is one of the major mechanisms for controlling
      cellular excitability. One of the main targets for this control at postsynaptic
      membranes is the G protein-coupled potassium channels (GIRK/Kir3), which generate
      slow inhibitory postsynaptic potentials following the activation of Pertussis
      toxin-sensitive G protein-coupled receptors. Using total internal reflection
      fluorescence (TIRF) microscopy combined with fluorescence resonance energy
      transfer (FRET), in intact cells, we provide evidence for the existence of a
      trimeric G protein-channel complex at rest. We show that activation of the
      channel via the receptor induces a local conformational switch of the G protein
      to induce channel opening. The presence of such a complex thus provides the means
      for a precise temporal and highly selective activation of the channel, which is
      required for fine tuning of neuronal excitability.

PMID- 16950156
TI  - RGS2 determines short-term synaptic plasticity in hippocampal neurons by
      regulating Gi/o-mediated inhibition of presynaptic Ca2+ channels.
AB  - RGS2, one of the small members of the regulator of G protein signaling (RGS)
      family, is highly expressed in brain and regulates G(i/o) as well as G(q)-coupled
      receptor pathways. RGS2 modulates anxiety, aggression, and blood pressure in
      mice, suggesting that RGS2 regulates synaptic circuits underlying animal
      physiology and behavior. How RGS2 in brain influences synaptic activity is
      unknown. We therefore analyzed the synaptic function of RGS2 in hippocampal
      neurons by comparing electrophysiological recordings from RGS2 knockout and wild
      type mice. Our study provides a general mechanism of the action of the RGS family
      containing RGS2 by demonstrating that RGS2 increases synaptic vesicle release by
      downregulating the G(i/o)-mediated presynaptic Ca(2+) channel inhibition and
      therefore provides an explanation of how regulation of RGS2 expression can
      modulate the function of neuronal circuits underlying behavior.

PMID- 16950157
TI  - The prototoxin lynx1 acts on nicotinic acetylcholine receptors to balance
      neuronal activity and survival in vivo.
AB  - Nicotinic acetylcholine receptors (nAChRs) affect a wide array of biological
      processes, including learning and memory, attention, and addiction. lynx1, the
      founding member of a family of mammalian prototoxins, modulates nAChR function in
      vitro by altering agonist sensitivity and desensitization kinetics. Here we
      demonstrate, through the generation of lynx1 null mutant mice, that lynx1
      modulates nAChR signaling in vivo. Its loss decreases the EC(50) for nicotine by
      approximately 10-fold, decreases receptor desensitization, elevates intracellular
      calcium levels in response to nicotine, and enhances synaptic efficacy. lynx1
      null mutant mice exhibit enhanced performance in specific tests of learning and
      memory. Consistent with reports that mutations resulting in hyperactivation of
      nAChRs can lead to neurodegeneration, aging lynx1 null mutant mice exhibit a
      vacuolating degeneration that is exacerbated by nicotine and ameliorated by null
      mutations in nAChRs. We conclude that lynx1 functions as an allosteric modulator
      of nAChR function in vivo, balancing neuronal activity and survival in the CNS.

PMID- 16950158
TI  - Mice deficient for the vesicular acetylcholine transporter are myasthenic and
      have deficits in object and social recognition.
AB  - An important step for cholinergic transmission involves the vesicular storage of
      acetylcholine (ACh), a process mediated by the vesicular acetylcholine
      transporter (VAChT). In order to understand the physiological roles of the VAChT,
      we developed a genetically altered strain of mice with reduced expression of this
      transporter. Heterozygous and homozygous VAChT knockdown mice have a 45% and 65%
      decrease in VAChT protein expression, respectively. VAChT deficiency alters
      synaptic vesicle filling and affects ACh release. Whereas VAChT homozygous mutant
      mice demonstrate major neuromuscular deficits, VAChT heterozygous mice appear
      normal in that respect and could be used for analysis of central cholinergic
      function. Behavioral analyses revealed that aversive learning and memory are not
      altered in mutant mice; however, performance in cognitive tasks involving object
      and social recognition is severely impaired. These observations suggest a
      critical role of VAChT in the regulation of ACh release and physiological
      functions in the peripheral and central nervous system.

PMID- 16950159
TI  - The insulin/PI 3-kinase pathway regulates salt chemotaxis learning in
      Caenorhabditis elegans.
AB  - The insulin-like signaling pathway is known to regulate fat metabolism, dauer
      formation, and longevity in Caenorhabditis elegans. Here, we report that this
      pathway is also involved in salt chemotaxis learning, in which animals previously
      exposed to a chemoattractive salt under starvation conditions start to show salt
      avoidance behavior. Mutants of ins-1, daf-2, age-1, pdk-1, and akt-1, which
      encode the homologs of insulin, insulin/IGF-I receptor, PI 3-kinase,
      phosphoinositide-dependent kinase, and Akt/PKB, respectively, show severe defects
      in salt chemotaxis learning. daf-2 and age-1 act in the ASER salt-sensing neuron,
      and the activity level of the DAF-2/AGE-1 pathway in this neuron determines the
      extent and orientation of salt chemotaxis. On the other hand, ins-1 acts in AIA
      interneurons, which receive direct synaptic inputs from sensory neurons and also
      send synaptic outputs to ASER. These results suggest that INS-1 secreted from AIA
      interneurons provides feedback to ASER to generate plasticity of chemotaxis.

PMID- 16950160
TI  - Subplate neurons regulate maturation of cortical inhibition and outcome of ocular
      dominance plasticity.
AB  - Synaptic plasticity during critical periods of development requires intact
      inhibitory circuitry. We report that subplate neurons are needed both for
      maturation of inhibition and for the proper sign of ocular dominance (OD)
      plasticity. Removal of subplate neurons prevents the developmental upregulation
      of genes involved in mature, fast GABAergic transmission in cortical layer 4,
      including GABA receptor subunits and KCC2, and thus prevents the switch to a
      hyperpolarizing effect of GABA. To understand the implications of these changes,
      a realistic circuit model was formulated. Simulations predicted that without
      subplate neurons, monocular deprivation (MD) paradoxically favors LGN axons
      representing the deprived (less active) eye, exactly what was then observed
      experimentally. Simulations also account for published results showing that OD
      plasticity requires mature inhibition. Thus, subplate neurons regulate molecular
      machinery required to establish an adult balance of excitation and inhibition in
      layer 4, and thereby influence the outcome of OD plasticity.

PMID- 16950161
TI  - Gradual translocation of spatial correlates of neuronal firing in the hippocampus
      toward prospective reward locations.
AB  - In a continuous T-maze alternation task, CA1 complex-spike neurons in the
      hippocampus differentially fire as the rat traverses overlapping segments of the
      maze (i.e., the stem) repeatedly via alternate routes. The temporal dynamics of
      this phenomenon were further investigated in the current study. Rats learned the
      alternation task from the first day of acquisition and the differential firing
      pattern in the stem was observed accordingly. More importantly, we report a
      phenomenon in which spatial correlates of CA1 neuronal ensembles gradually
      changed from their original firing locations, shifting toward prospective goal
      locations in the continuous T-maze alternation task. The relative locations of
      simultaneously recorded firing fields, however, were preserved within the
      ensemble spatial representation during this shifting. The within-session shifts
      in preferred firing locations in the absence of any changes in the environment
      suggest that certain cognitive factors can significantly alter the location-bound
      coding scheme of hippocampal neurons.

PMID- 16950162
TI  - Motor-sensory recalibration leads to an illusory reversal of action and
      sensation.
AB  - To judge causality, organisms must determine the temporal order of their actions
      and sensations. However, this judgment may be confounded by changing delays in
      sensory pathways, suggesting the need for dynamic temporal recalibration. To test
      for such a mechanism, we artificially injected a fixed delay between
      participants' actions (keypresses) and subsequent sensations (flashes). After
      participants adapted to this delay, flashes at unexpectedly short delays after
      the keypress were often perceived as occurring before the keypress, demonstrating
      a recalibration of motor-sensory temporal order judgments. When participants
      experienced illusory reversals, fMRI BOLD signals increased in anterior cingulate
      cortex/medial frontal cortex (ACC/MFC), a brain region previously implicated in
      conflict monitoring. This illusion-specific activation suggests that the brain
      maintains not only a recalibrated representation of timing, but also a less
      plastic representation against which to compare it.

PMID- 16950163
TI  - The radial bias: a different slant on visual orientation sensitivity in human and
      nonhuman primates.
AB  - It is generally assumed that sensitivity to different stimulus orientations is
      mapped in a globally equivalent fashion across primate visual cortex, at a
      spatial scale larger than that of orientation columns. However, some evidence
      predicts instead that radial orientations should produce higher activity than
      other orientations, throughout visual cortex. Here, this radial orientation bias
      was robustly confirmed using (1) human psychophysics, plus fMRI in (2) humans and
      (3) behaving monkeys. In visual cortex, fMRI activity was at least 20% higher in
      the retinotopic representations of polar angle which corresponded to the radial
      stimulus orientations (relative to tangential). In a global demonstration of
      this, we activated complementary retinotopic quadrants of visual cortex by simply
      changing stimulus orientation, without changing stimulus location in the visual
      field. This evidence reveals a neural link between orientation sensitivity and
      the cortical retinotopy, which have previously been considered independent.

PMID- 16950164
TI  - Semantic priming effects from single words in a lexical decision task.
AB  - The present research examines the semantic priming effects of a centrally
      presented single prime word to which participants were instructed to either
      "attend and remember" or "ignore". The prime word was followed by a central probe
      target on which the participants made a lexical decision task. The main variables
      manipulated across experiments were prime duration (50 or 100 ms), the presence
      or absence of a mask following the prime, and the presence (or absence) and type
      of distractor stimulus (random set of consonants or pseudowords) on the probe
      display. There was a consistent interaction between the instructions and the
      semantic priming effects. Relative to the "attend and remember" instruction, an
      "ignore" instruction produced reduced positive priming from single primes
      presented for 100 ms, irrespective of the presence or absence of a prime mask,
      and regardless of whether the probe target was presented with or without
      distractors. Additionally, reliable negative priming was found from ignored
      primes presented for briefer durations (50 ms) and immediately followed by a
      mask. Methodological and theoretical implications of the present findings for the
      extant negative priming literature are discussed.

PMID- 16950165
TI  - Adenosine deaminase and tuberculous pericarditis--a systematic review with meta
      analysis.
AB  - BACKGROUND: Adenosine deaminase (ADA) activity in pericardial fluid is a valuable
      aid in the diagnosis of tuberculous pericarditis (TP), but there is no systematic
      review performed to evaluate the benefits of ADA activity as an adjunctive test
      for TP diagnosis. The objective of this systematic review was to evaluate the
      utility of ADA activity as a diagnostic marker of TP on patients presenting with
      pericardial effusion. METHODS: MEDLINE, LILACS and Cochrane Library databases
      (1980-2005) searches to identify articles related to adenosine deaminase activity
      on TP diagnosis. Articles with patients with at least one TP diagnostic criteria
      were included. The controls were patients with other pericardial diseases with
      moderate or large pericardial effusion. To calculate the sensitivity,
      specificity, as well as positive and negative likelihood ratios we extracted the
      total number of confirmed TP cases over all patients with pericardial effusion as
      well as the number of cases with ADA activity values of 40 U/L and over. RESULTS:
      Thirty one studies met our initial inclusion criteria and five articles were
      selected. The heterogeneity limited the specificity analysis (p=0.004). The
      method yielded a sensitivity and specificity of 88% and 83%, respectively. The
      SROC curve presented an area with a tendency towards 1 (value of 0.9539) and
      corroborates the diagnostic value of ADA activity. CONCLUSIONS: The present study
      confirms the clinical value of ADA activity as adjunctive diagnostic marker of TP
      among other causes of pericardial effusion.

PMID- 16950166
TI  - Necrosis, a well-orchestrated form of cell demise: signalling cascades, important
      mediators and concomitant immune response.
AB  - Necrosis has long been described as a consequence of physico-chemical stress and
      thus accidental and uncontrolled. Recently, it is becoming clear that necrotic
      cell death is as well controlled and programmed as caspase-dependent apoptosis,
      and that it may be an important cell death mode that is both pathologically and
      physiologically relevant. Necrotic cell death is not the result of one well
      described signalling cascade but is the consequence of extensive crosstalk
      between several biochemical and molecular events at different cellular levels.
      Recent data indicate that serine/threonine kinase RIP1, which contains a death
      domain, may act as a central initiator. Calcium and reactive oxygen species (ROS)
      are main players during the propagation and execution phases of necrotic cell
      death, directly or indirectly provoking damage to proteins, lipids and DNA, which
      culminates in disruption of organelle and cell integrity. Necrotically dying
      cells initiate pro-inflammatory signalling cascades by actively releasing
      inflammatory cytokines and by spilling their contents when they lyse. Unravelling
      the signalling cascades contributing to necrotic cell death will permit us to
      develop tools to specifically interfere with necrosis at certain levels of
      signalling. Necrosis occurs in both physiological and pathophysiological
      processes, and is capable of killing tumour cells that have developed strategies
      to evade apoptosis. Thus detailed knowledge of necrosis may be exploited in
      therapeutic strategies.

PMID- 16950168
TI  - Impact of low high-density lipoproteins on in-hospital events and one-year
      clinical outcomes in patients with non-ST-elevation myocardial infarction acute
      coronary syndrome treated with drug-eluting stent implantation.
AB  - High-density lipoprotein (HDL) cholesterol has protective cardiovascular effects.
      We investigated the effect of baseline HDL cholesterol on the outcomes of
      patients who underwent drug-eluting stent implantation for acute coronary
      syndrome. Since March 2003, 1,032 consecutive patients were, according to their
      baseline HDL cholesterol level, included in a low HDL cholesterol group (n = 550,
      <40 mg/dl in men, <45 mg/dl in women, mean 32 +/- 7) or a high HDL cholesterol
      group (n = 482, >40 mg/dl in men, >45 mg/dl in women, mean 55 +/- 19). End points
      were death, Q-wave myocardial infarction, target lesion revascularization, and a
      composite of major adverse cardiac events at 30 days and 1 year. We assessed the
      relation between HDL cholesterol and end points. Patients with low HDL
      cholesterol more often had diabetes, a higher body mass index, higher
      triglyceride levels, and lower total cholesterol levels. Low-density lipoprotein
      cholesterol and statin treatment (98% in the 2 groups) were comparable.
      Incidences of mortality and major adverse cardiac events at 30 days were higher
      in the low than in the high HDL cholesterol group (p <0.001 and p = 0.002,
      respectively; chi-square analysis). At 1 year, more deaths occurred in the low
      HDL cholesterol group (p <0.001; chi-square analysis), as did major adverse
      cardiac events (p <0.001; chi-square analysis). Multivariate analysis showed low
      HDL cholesterol at baseline (hazard ratio 2.61, 95% confidence interval 1.33 to
      5.12) to be a key predictor of major adverse cardiac events and death (hazard
      ratio 3.33, 95% confidence interval 1.15 to 10.0) at 1 year. In conclusion,
      regardless of baseline low-density lipoprotein cholesterol levels and statin
      therapy, additional strategies to increase HDL cholesterol should be evaluated in
      patients with acute coronary syndrome.

PMID- 16950167
TI  - Probing the structure of Lhca3 by mutation analysis.
AB  - Lhc proteins constitute a family of transmembrane proteins which share homology
      in sequence and similarity in the general organisation although members can be
      strongly differentiated such as in the case of PsbS and ELIPs. In this work, we
      report on the structure of Lhca3, a pigment-protein subunit component of the
      antenna system of higher plants Photosystem I, through the effect of point
      mutations in critical sites. Based on the structure of PSI-LHCI (Ben Shem et al.,
      PDB file 1QZV remark 999) it has been suggested that Lhca3 may have different
      folding as compared to other members of the Lhc family. In particular, it was
      proposed that the two central helices may be swapped and chlorophylls in sites
      1013 and 1023 are not present. This different folding would imply that the
      chlorophylls coordinated to the two central helices have different ligands in
      Lhca3 with respect to the other Lhc complexes. The structural model was tested by
      substituting the putative binding residues with residues unable to coordinate
      chlorophyll and the spectroscopic properties of the individual pigments were used
      as structural probes. The results indicate that Lhca3 folds in the same way as
      the other antenna proteins. Moreover, the low-energy absorption form originates
      from interaction between chlorophylls in site 1015 and 1025, like for the other
      PSI antenna subunits. Evidence is also shown for the presence in Lhca3 of
      chlorophylls in sites 1013 and 1023.

PMID- 16950169
TI  - Effect of diabetes mellitus on five-year clinical outcomes after single-vessel
      coronary stenting (a pooled analysis of coronary stent clinical trials).
AB  - Diabetes mellitus (DM) increases the risk of clinically driven, repeat
      revascularization of the stented lesion in the first year after coronary
      stenting. The effect of DM on the risk of repeat revascularization of the stented
      lesion beyond 1 year, revascularization at other coronary sites, and clinical
      outcomes of cardiac death and myocardial infarction (MI) has not been reported.
      We pooled primary data from 4 multicenter trials of second-generation coronary
      stents that included 1,228 patients, 263 of whom (21%) had DM. Patients were
      followed annually to assess for prespecified end points, including repeat
      revascularization procedures, death, or MI. Repeat revascularization of the
      stented lesion was performed more frequently during the first year in patients
      with DM (16.0% vs 10.9%, p = 0.01) but decreased to a low frequency (1.8% vs 1.3%
      per year) thereafter in patients with and without DM. Repeat revascularization of
      other coronary segments was more frequent in patients with DM during the first
      and subsequent years (5-year rates, 32.2% vs 24.1%, p = 0.005). Cardiac death or
      MI was also more frequent among patients with DM (5-year rates, 25.4% vs 17.9%, p
      = 0.008) and remained significant after adjustment for all differences in
      baseline characteristics (hazard ratio 1.5, 95% confidence interval 1.1 to 2.0, p
      = 0.01). In conclusion, diabetic patients are at increased risk for
      revascularization of the stented lesion only in the first year after single
      lesion stenting but are at increased risk for other clinical events, including
      cardiac death and MI, over the next 4 years.

PMID- 16950170
TI  - Comparison of outcomes between bare metal stents and drug-eluting stents for
      percutaneous revascularization of internal mammary grafts.
AB  - Drug-eluting stents (DESs) decrease the need for repeat revascularization in
      native coronary arteries and vein grafts. This study examined the safety and
      efficacy of DESs for the treatment of lesions in the internal mammary artery
      (IMA) conduits and compared the outcomes with those from bare metal stents
      (BMSs). Records of 69 consecutive patients who underwent stenting of the IMA from
      2001 to 2004 were reviewed and analyzed. Of these, 30 patients were treated with
      DESs (sirolimus- or paclitaxel-eluting stents) and 39 patients with BMSs. In
      hospital and 6-month clinical outcomes were recorded and compared. Baseline
      characteristics were comparable between the 2 groups. Lesion location and
      characteristics were also similar, except for a trend toward longer stent lengths
      in the DES group (DES 20.2 +/- 7.7 mm vs BMS 14.8 +/- 3.5 mm, p = 0.255). There
      was no late thrombosis in either group. There were no significant differences in
      in-hospital and 1- and 6-month outcomes between the 2 groups, including target
      lesion revascularization with DESs (DESs 3.33% vs BMSs 10%, p = 0.38). In
      conclusion, DES implantation into IMAs appears safe and is associated with low
      rates of recurrences. These results may support expansion of use of DESs for the
      management of IMA stenotic lesions.

PMID- 16950171
TI  - Effect of impaired myocardial reperfusion on left ventricular remodeling in
      patients with anterior wall acute myocardial infarction treated with primary
      coronary intervention.
AB  - We assessed the effect of impaired myocardial blush after primary coronary
      intervention (PCI) on left ventricular remodeling in patients with ST-segment
      elevation myocardial infarction (STEMI). The study population consisted of 145
      patients with first anterior STEMI that was treated successfully (Thrombolysis In
      Myocardial Infarction grade 3 flow) with PCI. Left ventricular remodeling was
      defined as an increase of > or =20% in end-diastolic volume based on repeated
      echocardiographic measurements in patients. The study population was divided into
      2 groups according to the presence (myocardial blush grade [MBG] 2 to 3, n = 86)
      or absence (MBG 0 to 1, n = 59) of myocardial reperfusion. Left ventricular
      remodeling appeared in 21% of the entire study group. Poor myocardial blush after
      PCI was associated with an increased rate of remodeling compared with good
      myocardial reperfusion (32% vs 14%, hazard ratio 2.308, 95% confidence interval
      [CI] 1.21 to 4.39, p=0.014). Symptoms of heart failure were observed
      significantly more often in patients with MBG 0 to 1 (35.6% vs 18.6%, p = 0.032)
      than in patients with MBG 2 to 3. In multivariate analysis, only age (odds ratio
      0.96, 95% CI 0.92 to 0.99, p = 0.02) and MBG 0 to 1 (odds ratio 3.15, 95% CI 1.35
      to 7.31, p = 0.008) were associated with left ventricular dilation. In
      conclusion, impaired microvascular reperfusion is associated with left
      ventricular remodeling and development of congestive heart failure in patients
      with anterior STEMI that is treated with primary coronary angioplasty.

PMID- 16950172
TI  - Acute coronary syndrome may occur with in-stent restenosis and is associated with
      adverse outcomes (the PRESTO trial).
AB  - Patients with de novo acute coronary syndromes (ACSs) have a higher rate of
      adverse cardiac events and recurrent revascularization after percutaneous
      coronary interventions compared with patients who have stable angina. However, it
      is not known if an ACS presentation in patients with in-stent restenosis (ISR) is
      associated with a worse prognosis. Using the large PRESTO database of patients
      with ISR, we compared outcomes after successful percutaneous coronary
      intervention in 824 patients who presented with ACS with 617 patients who had
      stable angina. In-hospital and 9-month follow-up for myocardial infarction,
      target vessel revascularization, death, and a combined outcome of major adverse
      cardiac events (MACEs) were obtained. Follow-up angiographic results were also
      compared in those patients included in the angiographic substudy (140 patients
      with ACS and 99 with stable angina). Patients with ISR who presented with ACS
      were older and less often men, with higher incidences of diabetes, hypertension,
      tobacco use, previous coronary artery bypass graft surgery, and congestive heart
      failure. In-hospital complications were rare and similar in the 2 groups. At
      follow-up, patients with ACS had higher incidences of target vessel
      revascularization (33% vs 21%, p <0.001), MACEs (35% vs 22%, p <0.001), and
      angiographic restenosis (> or =50% narrowing, 56% vs 42%, p = 0.043). In
      multivariate analysis, after adjusting for baseline differences, an ACS
      presentation was associated with a higher incidence of long-term MACEs (odds
      ratio 1.66, 95% confidence interval 1.27 to 2.18, p <0.001). In conclusion, an
      ACS presentation in patients with ISR is associated with a higher incidence of
      recurrent adverse cardiovascular events and angiographic restenosis.

PMID- 16950173
TI  - Effect of body mass index on risk of long-term mortality following coronary
      artery bypass grafting.
AB  - The effect of obesity on long-term mortality after coronary artery bypass
      grafting (CABG) remains inconclusive, partly due to methodologic issues in
      previous studies. We examined the effect of obesity on long-term mortality (up to
      a 6-year follow-up) in adult patients with a body mass index (BMI) > or =18.5
      kg/m2 who underwent CABG at Baylor University Medical Center (Dallas, Texas)
      between January 1998 and August 1999 (n = 1,209). Unadjusted analysis indicated a
      strong association between BMI and long-term mortality (p = 0.001), with a
      decreased risk of mortality associated with increasing BMI. After adjusting for
      factors shown to be confounders of this relation (age, diabetes mellitus, chronic
      obstructive lung disease, renal failure, ejection fraction, and left main
      disease), the estimated association was no longer significant (p = 0.425). In
      conclusion, the apparent survival benefit associated with higher BMI became
      nonsignificant when the relation between mortality and BMI was adjusted, first
      for age and then for diabetes mellitus, chronic obstructive lung disease, renal
      failure, ejection fraction, and left main disease. This relation was masked in
      the crude analysis primarily by the effect of age. Patients with a high BMI were
      typically younger than patients with a lower BMI, suggesting that physicians and
      surgeons may only recommend/perform CABG for patients with a high BMI with an
      otherwise lower risk profile.

PMID- 16950174
TI  - Evaluation of the National Cholesterol Education Program Adult Treatment Panel
      III algorithm for selecting candidates for statin therapy: insights from the A to
      Z trial.
AB  - The National Cholesterol Education Program Adult Treatment Panel III recommends
      an algorithm to integrate iterative risk-stratification information with low
      density lipoprotein (LDL) cholesterol levels to identify candidates for statin
      therapy. We used the Aggrastat to Zocor (A to Z) trial, in which all patients
      presented with an acute coronary syndrome (ACS) event in the absence of previous
      statin therapy, to evaluate the performance of this algorithm. Of 1,750 patients
      with ACS included in this analysis, 1,126 (64%) had an indication for statin
      therapy before enrollment and 624 (36%) did not have a statin indication before
      enrollment. We estimate that initiating statin therapy at moderate dosages
      (decreasing LDL by 1 mmol/L) according to the National Cholesterol Education
      Program Adult Treatment Panel III guidelines would have prevented approximately
      15% of the ACS events leading to enrollment in the A to Z trial, whereas more
      intensive statin therapy (decreasing LDL by 1.5 mmol/L) would have prevented >21%
      of events. Aspirin use before enrollment was reported in only 38% of subjects
      with a statin indication. In conclusion, these observations represent missed
      opportunities for primary and secondary prevention and highlight the need for
      assessment of patient risk and better adherence to existing prevention
      guidelines.

PMID- 16950175
TI  - Effects of extended-release niacin on lipoprotein particle size, distribution,
      and inflammatory markers in patients with coronary artery disease.
AB  - In this study, niacin was added to existing therapy for 3 months in 54 subjects
      with stable coronary artery disease. Average total cholesterol, low-density
      lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride levels were
      similar between groups. Three months of niacin treatment increased total HDL by
      7.5% and decreased triglycerides by 15% compared with baseline values (p <0.005
      for each), whereas total cholesterol and LDL levels remained unchanged. Addition
      of niacin resulted in a 32% increase in large-particle HDL (p <0.001), an 8%
      decrease in small-particle HDL (p = 0.0032), an 82% increase in large-particle
      LDL (p = 0.09), and a 12% decrease in small-particle LDL (p = 0.008). Niacin
      decreased lipoprotein-associated phospholipase A2 and C-reactive protein levels
      (20% and 15%, respectively, p <0.05 for the 2 comparisons). No significant
      changes from baseline were seen in any tested parameter in subjects who received
      placebo. In conclusion, addition of niacin to existing medical regimens for
      patients with coronary artery disease and already well-controlled LDL levels
      favorably improves the distribution of lipoprotein particle sizes and
      inflammatory markers in a manner that would be expected to confer
      atheroprotection. The effect of altering lipoprotein particle distribution and
      inflammatory markers on surrogate markers of atherosclerosis and clinical
      cardiovascular events in this population remains unclear.

PMID- 16950176
TI  - Meta-analysis of data from the six primary prevention trials of cardiovascular
      events using aspirin.
AB  - Until recently, 5 major studies have formed the basis for the use of aspirin
      (acetylsalicylic acid) in primary prevention of cardiovascular (CV) events.
      Despite these data, the role of aspirin in primary prevention has not been
      established firmly. Six randomized trials have evaluated the benefits of aspirin
      for the primary prevention of CV events: the British Doctors' Trial, the
      Physicians' Health Study, the Thrombosis Prevention Trial, the Hypertension
      Optimal Treatment study, the Primary Prevention Project, and the Women's Health
      Study. The combined sample consists of 47,293 subjects on aspirin and 45,580 not
      on aspirin or placebo. A meta-analysis of these 6 trials assessed 6 CV end
      points: total coronary heart disease (CHD), nonfatal myocardial infarction (MI),
      total CV events, stroke, CV mortality, and all-cause mortality. No covariate
      adjustment was performed and appropriate tests for treatment effect,
      heterogeneity, and study size bias were applied. Using odds ratios and confidence
      intervals, the meta-analysis suggested superiority of aspirin for total CHD,
      nonfatal MI, and total CV events (p < or =0.001 in each case), with a
      nonsignificant trend (0.07 < p <0.34) for decreased risk of stroke, CV mortality,
      and all-cause mortality. There was no evidence of statistical bias (p >0.05).
      Given the study size and cohort, aspirin decreased the risk of CV events in this
      large patient sample. In conclusion, primary prevention with aspirin decreased
      the risk of total CHD, nonfatal MI, and total CV events, but there were no
      significant differences in the incidences of stroke or CV mortality.

PMID- 16950177
TI  - Effects of C-reactive protein and cholesterol on responsiveness in vitro of the
      internal thoracic artery to angiotensin II in patients having coronary artery
      bypass grafting.
AB  - The renin-angiotensin system is critically involved in the pathogenesis of
      atherosclerosis. Cholesterol increases vascular responsiveness to angiotensin II
      by upregulation of the angiotensin II type 1 receptor. However, the effects of C
      reactive protein (CRP) on vascular responsiveness to angiotensin II are unknown.
      We evaluated, in vitro, the vascular responsiveness of the internal thoracic
      artery to angiotensin II in patients who underwent coronary bypass grafting. We
      observed that increased preoperative CRP and increased cholesterol levels were
      strongly related to increased vascular responsiveness to angiotensin II (p <0.001
      for the 2 comparisons). However, angiotensin II-mediated contraction was
      increased only when levels of CRP and cholesterol were jointly increased. In
      conclusion, our results suggest that CRP and cholesterol act synergistically on
      vascular responsiveness to angiotensin II.

PMID- 16950178
TI  - Brachial reactivity and extent of coronary artery disease in patients with first
      ST-elevation acute myocardial infarction.
AB  - We examined peripheral endothelial function, as measured by brachial artery
      reactivity, in 49 stable patients with a first episode of acute ST-segment
      elevation myocardial infarction to examine the relation between extent of
      coronary disease and peripheral vascular reactivity. Brachial artery reactivity
      was assessed by ultrasound and flow-mediated dilation (FMD) was calculated as the
      change in brachial artery diameter after release of suprasystolic blood pressure
      cuff inflation. FMD was classified as abnormal in (< or =6%) 19 patients (group
      1) and as normal in 30 patients (group 2). Average FMDs were 2 +/- 2% in group 1
      and 11 +/- 4% in group 2. Patients in group 1 were older (62 +/- 5 vs 54 +/- 11
      years, p = 0.02) and more often had a history of hypertension (n = 10, 52%, vs 6,
      20%, p = 0.017). Patients with abnormal endothelial function (group 1) had a
      larger number of coronary obstructive (>or =50%) lesions (3.6 +/- 2.4 vs 2.0 +/-
      1.7, p = 0.01) and more extensive coronary disease (1.9 +/- 0.8 vs 1.4 +/- 0.8
      vessel disease, p = 0.05). In patients with 3-vessel disease, FMD was lower (4.0
      +/- 1.8% vs 8.2 +/- 0.8%, p = 0.04) than in those with lesser coronary
      involvement. In conclusion, in patients with a first episode of ST-segment
      elevation myocardial infarction, there was a strong correlation between extent of
      coronary artery disease and brachial artery reactivity. Patients with localized
      coronary disease had relatively normal brachial reactivity, whereas those with
      diffuse coronary disease had more severe abnormal brachial artery reactivity.

PMID- 16950179
TI  - Impact of ramipril on the circadian periodicity of acute myocardial infarction.
AB  - Onset of acute myocardial infarction (AMI) follows a diurnal periodicity, with a
      peak incidence between 6:00 a.m. and noon. Beta blockers and aspirin decrease the
      rate of AMI and blunt the peak incidence, but such an effect has not been
      evaluated for angiotensin-converting enzyme inhibitors. The effect of ramipril on
      onset of symptomatic AMI was evaluated in 4-hour periods over a 24-hour cycle in
      men and women who were > or =55 years of age, had cardiovascular disease or
      diabetes mellitus with > or =1 other risk factor, and participated in the Heart
      Outcomes Prevention Evaluation (HOPE) trial. During the 4.5-year follow-up, AMI
      was documented in 383 of 4,596 participants allocated to ramipril and in 491 of
      4,598 participants allocated to placebo (8.3% vs 10.7%, p <0.001). Ramipril
      decreased rates of AMI at each period and attenuated, but did not blunt, the peak
      incidence. In conclusion, inhibiting angiotensin-converting enzyme decreased AMI
      over a 24-hour period, but this enzyme does not seem to play a major role in the
      circadian periodicity of this acute event.

PMID- 16950180
TI  - Usefulness of clopidogrel in abolishing the increased risk of reinfarction
      associated with higher platelet counts in patients with ST-elevation myocardial
      infarction (results from CLARITY-TIMI 28).
AB  - Previous studies have demonstrated an association between increased baseline
      platelet counts and poorer clinical and angiographic outcomes in patients with ST
      elevation myocardial infarction (STEMI). We hypothesized that antiplatelet
      therapy would mitigate the effect of high baseline platelet counts on clinical
      outcomes. Data were obtained from 3,491 patients with STEMI in the CLARITY-TIMI
      28 trial. Patients were categorized into 3 groups based on their baseline
      platelet counts: <200 x 10(3)/microl (group 1), 200 to 300 x 10(3)/microl (group
      2), and >300 x 10(3)/microl (group 3). Among placebo-treated patients,
      reinfarction rates increased in a stepwise fashion as platelet counts increased
      (3.6%, 5.4%, and 9.0%, respectively, p for trend = 0.0025). When confounders of
      high platelet counts and correlates of reinfarction were adjusted for in a
      multivariate model, high platelet counts remained independently associated with
      increased rates of reinfarction at 30 days in placebo-treated patients; using
      group 1 as a reference group, multivariate odds ratios were 1.45 (95% confidence
      interval 0.91 to 2.31, p = 0.119) for patients in group 2 and 1.78 (95%
      confidence interval 1.03 to 3.08, p = 0.038) for patients in group 3. In
      contrast, among clopidogrel-treated patients, there was no increase in the risk
      of reinfarction as the platelet count increased (3.2%, 4.1%, and 3.3%,
      respectively; p for trend = 0.9073, p for interaction=0.064). In conclusion,
      among patients with STEMI who are treated with aspirin and a fibrinolytic agent,
      high platelet counts on presentation are independently associated with increased
      rates of reinfarction. Clopidogrel therapy abolishes this increase in the risk of
      reinfarction as platelet counts increase. These data are consistent with a
      putative role of platelets in reinfarction.

PMID- 16950181
TI  - Integration of B-type natriuretic peptide levels with clinical data and exercise
      testing for predicting coronary artery disease.
AB  - Natriuretic peptides have been shown to be high in patients with myocardial
      ischemia. We sought to create a diagnostic score using clinical data, stress
      testing, and B-type natriuretic peptide (BNP) levels to improve noninvasive
      prediction of coronary artery disease (CAD). Patients with stable angina pectoris
      and normal systolic left ventricular function were eligible for this prospective
      cohort study. Patients with arrhythmias, valvular heart disease, impaired left
      ventricular function, or renal dysfunction were excluded. All patients underwent
      clinical evaluation, bicycle stress testing, BNP testing, and coronary
      angiography. Then a diagnostic risk score was derived that combined
      cardiovascular risk factors, results of exercise testing, and BNP measurements
      and added 1 point for the presence of each of these variables. Seventy-one
      patients (52 years of age, range 31 to 61; 46 men) were included in the study.
      Prevalence of CAD, defined by 50% narrowing of > or =1 coronary artery on
      coronary angiography, was 45%. For 0 point in the risk score system, the negative
      predictive value was 93% with a negative likelihood ratio of 0.1 (95% confidence
      interval [CI] 0.02 to 0.38); for a score of 3 points, the positive predictive
      value was 93% with a positive likelihood ratio of 15.9 (95% CI 2.19 to 114.7).
      Serum BNP level >50 ng/L at rest was the best single diagnostic parameter, with
      66% sensitivity and 97% specificity, and a positive likelihood ratio of 25.6 (95%
      CI 3.64 to 180) and a negative likelihood ratio of 0.35 (95% CI 0.22 to 0.57). In
      conclusion, a diagnostic score combining exercise testing, clinical data, and
      serum BNP values at rest can distinguish patients with CAD from those without CAD
      with high accuracy.

PMID- 16950182
TI  - Comparison of rosuvastatin versus atorvastatin in Hispanic-Americans with
      hypercholesterolemia (from the STARSHIP trial).
AB  - In a multicenter, open-label trial, 696 Hispanic patients with low-density
      lipoprotein (LDL) cholesterol levels > or =130 and < or =300 mg/dl and
      triglyceride levels <400 mg/dl at medium or high risk of coronary heart disease
      were randomized to receive 10 or 20 mg of rosuvastatin or 10 or 20 mg of
      atorvastatin for 6 weeks. At week 6, LDL cholesterol was decreased more by 10 mg
      of rosuvastatin than by 10 mg of atorvastatin (45% vs 36%, p <0.0001) and more by
      20 mg of rosuvastatin than by 20 mg of atorvastatin (50% vs 42%, p <0.0001).
      Significantly greater decreases were also observed with rosuvastatin for total
      cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein-B, and
      lipid ratios compared with milligram-equivalent doses of atorvastatin. Overall,
      National Cholesterol Education Program Adult Treatment Program III LDL
      cholesterol goals were achieved by 78% and 88% of patients who received 10 and 20
      mg of rosuvastatin and by 60% and 73% of patients who received 10 and 20 mg of
      atorvastatin, respectively. Among high-risk patients, the LDL cholesterol goal of
      <100 mg/dl was achieved by 74% and 91% of patients who received 10 and 20 mg of
      rosuvastatin and by 52% and 62% who received 10 and 20 mg of atorvastatin,
      respectively. All treatments were well tolerated, and adverse events were similar
      in frequency across treatment groups. No cases of myopathy or rhabdomyolysis were
      observed. In conclusion, treatment with rosuvastatin and atorvastatin produced
      beneficial lipid changes in this group of Hispanic patients that appear
      comparable in magnitude to those observed in primarily non-Hispanic white study
      populations. These benefits were accompanied by a favorable safety profile that
      suggests no concerns particular to this population.

PMID- 16950183
TI  - Relation between atherosclerosis risk factors and aspirin resistance in a primary
      prevention population.
AB  - Resistance to inhibition of platelet function by aspirin may contribute to future
      myocardial infarction and stroke. Adverse cardiovascular outcomes have been
      associated with aspirin resistance on several different platelet function assays,
      including the level of urinary 11-dehydro thromboxane B2 (Tx-M), platelet
      aggregation to arachidonic acid and adenosine diphosphate, and closure time on
      the platelet function analyzer-100. We examined the concordance of these aspirin
      resistance assays and their relation to cardiovascular risk factors in a primary
      prevention population. Asymptomatic patients (n = 1,311) at increased risk for
      coronary heart disease were evaluated before and after 2 weeks of aspirin (81
      mg/day). Aspirin resistance was defined according to published criteria for these
      3 assays of platelet function. Subjects were characterized for the presence of
      atherosclerosis risk factors. Agreement among the 3 assays was poor. Only 5
      patients met aggregation criteria for aspirin resistance. Attenuated suppression
      of urinary Tx-M by aspirin was associated with a greater atherosclerotic risk
      profile and Framingham risk score in multivariable regression analysis. Aspirin
      resistance by platelet function analyzer-100 was associated only with increased
      von Willebrand factor levels and not with atherosclerotic risk profile. In
      conclusion, in a primary prevention population, different published criteria for
      aspirin resistance classify distinct groups of patients as aspirin resistant with
      very little overlap. Higher Tx-M, which reflects decreased suppression of
      thromboxane production in vivo, is the only criterion associated with
      atherosclerosis risk factors, suggesting that this measurement may represent the
      most relevant approach for identifying asymptomatic subjects whose aspirin
      treatment will "fail."

PMID- 16950184
TI  - Usefulness of atrioventricular delay optimization using Doppler assessment of
      mitral inflow in patients undergoing cardiac resynchronization therapy.
AB  - This study evaluated the utility of atrioventricular (AV) optimization using
      Doppler echocardiography in patients who undergo cardiac resynchronization
      therapy (CRT). AV optimization in patients who undergo CRT is performed
      inconsistently, with few data supporting its utility. Data were collected from
      215 patients in New York Heart Association class III or IV heart failure (66%
      ischemic) who underwent AV optimization <30 days after implantation from 1999 to
      2003. All patients arrived with AV delay programmed at the time of their CRT
      procedures (100 to 120 ms). AV delay was optimized using Doppler mitral inflow
      data to target stage I diastolic filling. Baseline clinical characteristics, AV
      delay, and diastolic functional stage were recorded. The mean follow-up period
      was 23 months. Five hundred patients underwent CRT, 215 of whom underwent AV
      optimization <30 days after implantation. Baseline mean age was 66 +/- 12 years,
      left ventricular (LV) ejection fraction 19 +/- 8%, LV end-diastolic dimension 6.5
      +/- 1 cm, LV end-systolic dimension 5.5 +/- 1 cm, QRS duration 166 +/- 27 ms, and
      time to AV optimization 2.5 +/- 4 days. Baseline and final AV delay means were
      120 +/- 25 and 135 +/- 40 ms, respectively (p = 0.0001). In 40% of patients (86
      of 215), final AV delay settings were >140 ms. Left atrial diameter and AV block
      predicted patients in whom AV delay settings >140 ms were optimal. There was no
      difference in mortality in patients with final AV delays of >140 ms. In
      conclusion, AV optimization in patients who underwent CRT resulted in final AV
      delay settings of >140 ms in 40% of patients. AV delay optimization based on
      Doppler echocardiographic determination of optimal diastolic filling is useful
      and safe in patients who undergo CRT.

PMID- 16950185
TI  - Association of Duke prognostic treadmill scores with change in P-wave duration
      during exercise tolerance tests in patients with interatrial block and coronary
      heart disease.
AB  - Interatrial block (IAB), as denoted by P waves > or =110 ms in duration, is
      believed to be associated with underlying ischemia, particularly with that of its
      principal interatrial conduction pathway, the Bachmann bundle. In this study, the
      association between Duke prognostic treadmill (DPT) scores and change in P-wave
      duration in IAB was investigated in patients who underwent cardiopulmonary
      exercise tolerance tests (CPETTs). Twenty-seven patients with IAB and 42 control
      patients without IAB on electrocardiography at rest who had evidence of
      myocardial ischemia on coronary angiography after CPETTs were identified
      consecutively. P-wave measurements were obtained independently at the beginning
      of every CPETT stage and also when P-wave changes occurred. Increments in P-wave
      durations were measured to the nearest 20 ms. DPT scores were calculated for the
      2 groups. There was no significant difference between the groups in mean values
      for DPT scores and for exercise capacity. However, change in P-wave duration in
      patients with IAB was significantly associated with mean DPT score. As the change
      in P-wave duration increased, the DPT score was significantly less (p = 0.003).
      DPT scores were more significant with P-wave changes of >20 ms compared with P
      wave changes of < or =20 ms (p = 0.00001). In conclusion, in patients with
      coronary heart disease and IAB at rest, increases in P-wave durations during
      CPETTs are inversely associated with DPT scores.

PMID- 16950186
TI  - Comparison of cardiac and peripheral arterial stiffening and ventriculovascular
      uncoupling in patients with uncomplicated hypertension versus patients with
      hypertension after heart transplantation.
AB  - Despite normal ejection fractions, patients who undergo heart transplantation
      (HT) have low peak aerobic capacity and reduced arterial compliance, suggesting
      "ventriculovascular uncoupling." To what extent this is related to post
      transplantation hypertension versus the unique characteristics of the donor
      recipient relation remains poorly understood. Echocardiograms were
      retrospectively reviewed from 126 normal subjects, 309 patients with
      uncomplicated hypertension (UH), and 58 consecutive patients with HT >1 year
      after the procedure who were stable without evidence of rejection. Left
      ventricular (LV) end-systolic elastance (Ees), a measure of LV systolic
      performance; effective arterial elastance (Ea), a measure of vascular stiffness;
      and Ea/Ees, a parameter describing ventriculovascular coupling, were obtained.
      Compared with normal subjects, tandem increases in Ea (+24% and +85%, all p
      values <0.0001) and Ees (+23% and +33%, all p values <0.0001) were observed in
      patients with UH and HT, respectively, with patients with HT having significantly
      higher values than those with UH (both p values <0.05). Although the Ea/Ees ratio
      remained similar between normal subjects and patients with UH, patients with HT
      exhibited increases in the Ea/Ees ratio (all p values <0.01) and reduced stroke
      volume indexes (-20% and -22%, respectively, all p values <0.05). These changes
      were associated with a doubling of LV concentric remodeling in patients with HT
      compared with those with UH (67% vs 34%, p <0.0001). In conclusion, HT is
      associated with increases in Ees, Ea, and the Ea/Ees ratio, suggesting
      ventriculovascular uncoupling and maximal LV stroke work. These aberrations,
      which determine cardiovascular performance in the setting of HT, are not simply
      explained by vascular age or post-transplantation hypertension but may adversely
      affect functional capacity.

PMID- 16950187
TI  - Risk of venous thromboembolism in patients hospitalized with heart failure.
AB  - Because of uncertainty about the prevalence of pulmonary embolism (PE) and deep
      venous thrombosis (DVT) in hospitalized patients with congestive heart failure
      (CHF), data from the National Hospital Discharge Survey were investigated. Among
      hospitalized patients with CHF, PE was diagnosed in 0.73% and DVT in 1.03%. The
      relative risk for PE in patients with CHF compared with patients with no CHF was
      2.15; for DVT, it was 1.21. The relative risk for PE in patients with CHF was
      greatest in patients <40 years of age (relative risk 11.72), and the relative
      risk for DVT was 5.46. In conclusion, a high relative risk for PE, DVT, and
      venous thromboembolism was shown in patients with CHF who were <60 years of age.

PMID- 16950188
TI  - Plasma myeloperoxidase levels in patients with chronic heart failure.
AB  - Increased oxidative stress and endothelial dysfunction are commonly observed in
      patients with chronic heart failure (HF). The relation between myeloperoxidase
      (MPO), an inflammatory marker with mechanistic links to plaque vulnerability and
      abnormal ventricular remodeling, and degrees of severity in chronic HF has not
      been reported. Plasma MPO levels were measured in 105 normal controls (no history
      of HF or left ventricular dysfunction) and 102 patients with chronic systolic HF
      (left ventricular ejection fraction <50%), and the relations among plasma MPO
      levels, plasma B-type natriuretic peptide levels, and the left ventricular
      ejection fraction were examined. Plasma MPO levels in patients with chronic
      systolic HF were significantly elevated compared with those of healthy controls
      (1,158 +/- 2,965 vs 204 +/- 139 pM, p <0.0001). Plasma MPO levels increased in
      parallel with increasing New York Heart Association class (p <0.0001) and were
      correlated with plasma B-type natriuretic peptide levels (Spearman's r = 0.39, p
      <0.0001). Levels of MPO were strongly associated with the prevalence of HF
      (unadjusted odds ratio 30.3, 95% confidence interval 11.1 to 94.5) and remained
      significant when adjusted for age and B-type natriuretic peptide (odds ratio
      27.7, 95% confidence interval 3.6 to 371.1). In conclusion, in a cohort of
      patients with chronic HF, plasma MPO levels were elevated compared with those of
      normal controls and were associated with worsening functional class.

PMID- 16950189
TI  - Cost-effectiveness of using N-terminal pro-brain natriuretic peptide to guide the
      diagnostic assessment and management of dyspneic patients in the emergency
      department.
AB  - The cost-effectiveness of N-terminal pro-brain natriuretic peptide (NT-pro-BNP)
      in dyspneic patients in emergency departments (EDs) is unknown. The objective of
      this study was to assess the cost-effectiveness of NT-pro-BNP testing for the
      evaluation and initial management of patients with dyspnea in the ED setting. A
      decision model was developed to evaluate the cost-effectiveness of diagnostic
      assessment and patient management guided by NT-pro-BNP, compared with standard
      clinical assessment. The model includes the diagnostic accuracy of the 2
      strategies for congestive heart failure and resulting events at 60-day follow-up.
      Clinical data were obtained from a prospective blinded study of 599 patients
      presenting to the ED with dyspnea. Costs were based on the Massachusetts General
      Hospital cost accounting database. The model predicted serious adverse events
      during follow-up (i.e., urgent care visits, repeat ED presentations,
      rehospitalizations) and direct medical costs for echocardiograms and
      hospitalizations. NT-pro-BNP-guided assessment was associated with a 1.6%
      relative reduction of serious adverse event risk and a 9.4% reduction in costs,
      translating into savings of $474 per patient, compared with standard clinical
      assessment. In a sensitivity analysis considering mortality, NT-pro-BNP testing
      was associated with a 1.0% relative reduction in post-discharge mortality. The
      optimal use of NT-pro-BNP guidance could reduce the use of echocardiography by up
      to 58%, prevent 13% of initial hospitalizations, and reduce hospital days by 12%.
      In conclusion, on the basis of this model, the use of NT-pro-BNP in the
      diagnostic assessment and subsequent management of patients with dyspnea in the
      ED setting could lead to improved patient care while providing substantial cost
      savings to the health care system.

PMID- 16950190
TI  - Comparison of African-American patients with systolic heart failure versus
      preserved ejection fraction.
AB  - Evidence exists for race-specific differences in the cause and natural history of
      heart failure (HF). These differences may have important treatment implications,
      but relatively limited data on African-Americans exist. A cohort of 89 African
      American patients admitted to an urban teaching hospital with diagnoses of HF was
      examined. Most patients had systolic HF (71%), and the remainder had HF with
      preserved ejection fractions (EFs). Patients with HF with preserved EFs tended to
      be generally older (67 vs 57 years, p = 0.01) and were more likely to be women
      (69% vs 42%, p = 0.02). There were no significant differences between patients
      with systolic HF and those with HF with preserved EFs in the prevalence of
      coronary artery disease (23%), diabetes mellitus (44%), or chronic obstructive
      pulmonary disease (38%). Gastrointestinal bleeding and anemia were significant
      contributors to admission in patients with preserved EFs, with baseline
      hematocrits being significantly lower (34.9 vs 38.3, p = 0.01). On discharge,
      patients with HF with preserved EFs were less likely to be prescribed angiotensin
      converting enzyme inhibitors than patients with systolic HF (65% vs 83%, p =
      0.08) or diuretics (58% vs 82.%, p = 0.03). In conclusion, differences exist in
      African-American patients who present with HF; optimal therapeutic approaches
      will require a better understanding of their underlying pathophysiology.

PMID- 16950191
TI  - Prognostic value of preoperative atrial fibrillation in patients with aortic
      stenosis and low ejection fraction having aortic valve replacement.
AB  - Aortic valve replacement in severe aortic stenosis (AS) with a low left
      ventricular ejection fraction (EF) is associated with high perioperative
      mortality. The aim of this study was to assess the prognostic value of
      preoperative atrial fibrillation (AF) in patients with AS and low EFs who undergo
      aortic valve replacement. Eighty-three consecutive patients with severe AS (area
      <1 cm2) and low EFs (< or =35%) were prospectively included. Perioperative
      mortality was 12%. Twenty-nine patients (35%) had preexisting paroxysmal or
      permanent AF. Perioperative mortality was higher in the AF group than in the non
      AF group (24% vs 5.5%, p = 0.03). Preoperative AF was identified as an
      independent predictor of perioperative mortality (odds ratio 7.5, 95% confidence
      interval 1.19 to 47.06, p = 0.03). Five-year overall survival was lower in the AF
      group than in the non-AF group (47% vs 77%, p = 0.0017). Associated multivessel
      coronary artery disease and preoperative AF were identified as 2 independent
      predictors of overall mortality. In conclusion, in patients with AS with low left
      ventricular EFs, preoperative AF is associated with higher operative risk and
      lower postoperative survival. The presence of AF in patients with severe AS and
      low EFs should be taken into account for operative risk stratification, along
      with low pressure gradient and associated multivessel coronary artery disease.

PMID- 16950192
TI  - Immediate and long-term follow-up of percutaneous balloon mitral valvuloplasty in
      pregnant patients with rheumatic mitral stenosis.
AB  - Percutaneous mitral balloon valvuloplasty (PMV) can be performed during pregnancy
      without significant maternal risk or fetal morbidity or mortality. However,
      little is known about long-term follow-up results after PMV in populations of
      pregnant women. Thus, the present study was undertaken to determine the immediate
      and long-term outcomes after PMV in a large cohort of pregnant patients with
      severe mitral stenosis. The patient population consisted of 71 consecutive
      pregnant women with severe rheumatic mitral stenosis admitted to the hospital
      with severe congestive heart failure (New York Heart Association class III and
      IV) for PMV. All patients underwent clinical and obstetric evaluations,
      electrocardiography, and 2-dimensional and Doppler echocardiography. PMV was
      successful in all patients, resulting in a significant increase in mitral valve
      area from 0.9 +/- 0.2 to 2.0 +/- 0.3 cm2 (p <0.001). At the end of pregnancy, 98%
      of the patients were in New York Heart Association functional class I or II. At a
      mean follow-up of 44 +/- 31 months, the total event-free survival rate was 54%.
      The mean gestational age at delivery time was 38 +/- 1 weeks. Preterm deliveries
      occurred in 9 patients (13%), including 2 twin pregnancies. The remaining 66 of
      75 newborns (88%) had normal weight (mean 2.8 +/- 0.6 kg) at delivery. At long
      term follow-up of 44 +/- 31 months after birth, the 66 children exhibited normal
      growth and development and did not show any clinical abnormalities. In
      conclusion, PMV is safe and effective, has a low morbidity and mortality rate for
      the mother and the fetus, and has favorable long-term results in pregnant women
      with rheumatic mitral stenosis in New York Heart Association functional class III
      or IV.

PMID- 16950193
TI  - Plasma soluble osteopontin concentrations are increased in patients with
      rheumatic mitral stenosis and associated with the severity of mitral valve
      calcium.
AB  - Although the severity of valvular calcification is an important prognostic
      indicator, the cellular mechanisms of the calcification process are unknown.
      Osteopontin modulates inflammation and biomineralization, and increased
      osteopontin expression has been demonstrated in calcified degenerative or
      rheumatic cardiac valves. The present study evaluated soluble plasma osteopontin
      in 32 patients with echocardiographically determined rheumatic mitral stenosis
      and compared the results to those of a control group of 22 healthy patients.
      Patients were evaluated with routine echocardiographic techniques, Wilkins
      scoring, and 2-dimensional echocardiographic calcium scoring. Patients with
      rheumatic involvement other than in the mitral valve were excluded. Plasma
      osteopontin and high-sensitivity C-reactive protein levels in patients with
      mitral stenosis were significantly higher those of the control group (p = 0.006
      and p = 0.0001, respectively). A significant correlation was found between plasma
      osteopontin levels and the severity of mitral valve calcification (p = 0.003) and
      also between high-sensitivity C-reactive protein levels and Wilkins score (p =
      0.009). There was a stepwise and statistically significant increase in soluble
      plasma osteopontin levels in association with the severity of mitral valve
      calcification. In conclusion, increased osteopontin levels were correlated with
      the severity of mitral valve calcification in patients with rheumatic mitral
      stenosis, suggesting an important role of osteopontin in the modulation of
      valvular calcification. Elevated levels of high-sensitivity C-reactive protein
      concentrations suggest the presence of ongoing inflammation in those patients.

PMID- 16950194
TI  - Different types of cardiomyopathy associated with isolated ventricular
      noncompaction.
AB  - Although mainly described in the context of dilated and hypokinetic left
      ventricles, it is unclear whether isolated ventricular noncompaction (IVNC) is a
      distinct cardiomyopathy, a subtype of dilated cardiomyopathy, or a morphogenetic
      disorder. To investigate the spectrum of cardiomyopathies associated with IVNC,
      children and adults with stringent echocardiographic diagnoses of IVNC were
      reviewed. Seventy-three patients (12 children aged <15 years) seen since 1994
      satisfied stringent echocardiographic criteria for IVNC. Sixty-five patients
      (89%; 11 children) had dilated cardiomyopathy, 2 adults had clear-cut
      hypertrophic cardiomyopathy, 1 adult had restrictive cardiomyopathy (to the
      investigators' knowledge, the first reported example of this particular
      association), and 5 patients (1 child) had normal left ventricular morphology and
      function. In conclusion, knowledge that IVNC can co-exist with restrictive and
      hypertrophic cardiomyopathy (in addition to the dilated form) supports the
      concept that IVNC is a morphologic trait rather than a distinct cardiomyopathy.
      This knowledge should be taken into account during echocardiographic examination
      and encourage the use of contrast echocardiography (and magnetic resonance) and
      could also orient molecular biology studies.

PMID- 16950195
TI  - Left ventricular function and response to enalapril in patients with duchenne
      muscular dystrophy during the second decade of life.
AB  - The role of angiotensin-converting enzyme inhibitors in the management of
      cardiomyopathy related to Duchenne muscular dystrophy has not been completely
      defined. The purposes of this study were to describe the response to enalapril
      and its relation to dystrophin mutation type, ventricular size, or age at the
      onset of left ventricular (LV) systolic dysfunction. Serial clinical and
      echocardiographic data from 50 patients with Duchenne muscular dystrophy (aged 10
      to 20 years) were retrospectively reviewed. Twenty-seven patients (46%) developed
      LV systolic dysfunction (mean age 13.2 +/- 2.4 years). Ten (43%) responded to
      enalapril with the normalization of function. Responders and nonresponders
      developed LV systolic dysfunction at similar ages (p = 0.91). At the onset of LV
      systolic dysfunction, only 2 patients (1 responder, 1 nonresponder) had dilated
      left ventricles. The positive response to enalapril was sustained in 7 patients
      (median follow-up 23 months, range 5 to 58). No specific mutation was associated
      with the response to enalapril (p = 0.66) or predictive of the development of LV
      systolic dysfunction (p = 0.8). In conclusion, 10 of 26 patients (43%) with
      Duchenne muscular dystrophy responded to the use of enalapril with normalization
      of the shortening fraction. Age at the onset of LV systolic dysfunction and the
      type of mutation were not predictors of response to enalapril.

PMID- 16950196
TI  - Progression of aortic dilation in children with a functionally normal bicuspid
      aortic valve.
AB  - Adults with bicuspid aortic valves (BAVs) are at risk for progressive aortic
      dilation independent of valve function. The evolution of aortic dilation in
      children with functionally normal BAVs has not been studied. In this study,
      ascending aortic diameters were assessed in a group of children with functionally
      normal BAVs (peak gradient < or =16 mm Hg) to determine whether progressive
      dilation occurs during childhood. A cohort of 101 patients and 97 controls were
      studied with echocardiography. There were no differences in mean age (9.0 +/- 4.8
      vs 8.7 +/- 6.1 years, p = 0.7) or body surface area (1.1 +/- 0.4 vs 1.1 +/- 0.5
      m2, p = 0.9). Patients had significantly greater aortic dimensions than controls
      in all measured regions of the aorta, with the most striking discrepancy in the
      ascending aorta (2.3 +/- 0.6 vs 1.8 +/- 0.5 cm, p <0.0001). The size discrepancy
      was present from birth and persisted throughout childhood. Repeated measurements
      were performed in a subgroup of 28 patients and 25 controls. Patients had
      significantly greater increases in ascending aortic dimension than controls per
      year of follow-up (1.2 +/- 0.08 vs 0.6 +/- 0.08 mm/year, p <0.0001). In
      conclusion, BAV is complicated by progressive aortic dilation beginning in
      childhood.

PMID- 16950197
TI  - Relation of atrial shunts to migraine in patients with ischemic stroke and
      peripheral emboli.
AB  - This study investigated whether the increased incidence of stroke in young
      subjects with migraine is because they have an increased prevalence of atrial
      right-to-left shunts. The investigators report the prevalence of clinically
      relevant atrial shunts in those with stroke and migraine compared with those with
      stroke but without migraine and also in historic control groups of subjects who
      had migraine with aura but no stroke and in population controls. Of 60
      consecutive stroke patients, 42 (70%) had large- or medium-sized atrial shunts.
      Transcatheter shunt closure was performed in 39 patients, of whom 35 had patent
      foramen ovales (mean diameter 9.8 +/- 4.1 mm) and 4 had atrial septal defects. If
      atrial shunts were unrelated to stroke in patients with migraines, shunt
      prevalence in those with migraine and stroke would be the same as in those with
      migraine but without stroke. However, a much greater shunt prevalence was found
      in those with stroke and migraine with aura (84%) than in those with migraine
      with aura but no stroke (38.1%, p <0.001), population controls (12.2%, p <0.001),
      and those with stroke but no migraine (55.6%, p <0.05). Shunt prevalence was also
      significantly greater in patients who had stroke and migraine without aura (75%)
      than in population controls (p <0.001) and in those with migraine with aura but
      no stroke (p <0.05). In conclusion, the increased incidence of stroke in subjects
      with migraine compared with the general population is because they have a higher
      prevalence of large atrial shunts and hence an increased risk for paradoxic
      embolism.

PMID- 16950198
TI  - Gender differences in left ventricular systolic function in American Indians
      (from the Strong Heart Study).
AB  - Data from population-based studies indicate that men have a higher incidence and
      worse prognoses of congestive heart failure than women. Echocardiography was used
      to compare left ventricular (LV) myocardial and chamber contractility between 490
      male and 861 female American Indian participants in the second Strong Heart Study
      examination. After adjusting for fat-free mass, baseline hypertension, diabetes
      mellitus, coronary heart disease, and alcohol consumption, LV ejection fractions
      were higher in women than men (66 +/- 8% vs 63 +/- 9%, p = 0.002), as were stress
      corrected mid-wall shortening (106 +/- 13% vs 104+/-15%, p = 0.006) and the
      circumferential end-systolic stress/end-systolic volume index (7.1 x 10(4) +/-
      1.9 x 10(4) vs 6.5 x 10(4) +/- 2.1 x 10(4) kdyne/cm3, all p values <0.001). LV
      ejection fractions were less than the predefined partition value in 4.7% of women
      and in 16.7% of men (odds ratio 0.25, 95% confidence interval 0.18 to 0.34, p
      <0.001). Stress-corrected mid-wall shortening was less than the predetermined
      lower limit of normal in 2.9% of women and in 6.2% of men (odds ratio 0.45, 95%
      confidence interval 0.29 to 0.70, p <0.001). There was no significant gender
      difference in supranormal function by either measure of LV systolic function.
      Estimated mean independent effects of female gender were a 3% greater ejection
      fraction, 2.7% greater stress-corrected mid-wall shortening, and a 0.4 x 10(4)
      kdyne/cm3 greater circumferential end-systolic stress/end-systolic volume index.
      In conclusion, in a population-based sample aged 45 to 74 years, women had
      greater LV myocardial and chamber function than men. Gender-specific partition
      values for measures of LV systolic function may be necessary to detect abnormal
      contractility in clinical and epidemiologic studies.

PMID- 16950199
TI  - Effect of aspirin dose, preparation, and withdrawal on platelet response in
      normal volunteers.
AB  - A significant difference in individual response to aspirin therapy has been
      described, and studies have shown that a minimal response to aspirin may be
      associated with increased risk for some cardiovascular events. However, it
      remains unclear if aspirin dose, coating, or termination alters the antiplatelet
      effects of aspirin. Normal volunteers were randomly assigned to enteric-coated or
      uncoated aspirin 81 or 325 mg and monitored over 12 days with a point-of-care
      aspirin assay that incorporates the platelet agonist arachidonic acid. The
      antiplatelet response was greater with a 325-mg dose than with an 81-mg dose. A
      coating slowed the antiplatelet response to the 81-mg dose only. There were no
      differences among the groups after maximum response was achieved between days 4
      and 7. There was significant recovery of platelet aggregation <48 hours after the
      cessation of aspirin, with a return to baseline values by the fifth day. A
      significant interpatient variation in response to the 4 dosing regimes was
      observed. In conclusion, the antiplatelet response was more rapid to a 325-mg/day
      dose of aspirin compared with an 81-mg/day dose. An enteric-coated preparation
      delayed the time of response to an 81-mg/day dose. These results suggest that
      aspirin dose and preparation may be important mediators of the antiplatelet
      effects of aspirin in some patients.

PMID- 16950200
TI  - The Editor's roundtable: diabetes mellitus and coronary heart disease.

PMID- 16950201
TI  - Inhibition of human tumor xenograft growth in nude mice by a conjugate of
      monoclonal antibody LA22 to epidermal growth factor receptor with anti-tumor
      antibiotics mitomycin C.
AB  - Anti-EGFR monoclonal antibodies LA22 and Erbitux bind to different epitopes of
      EGFR. The chemimmunoconjugates of MMC with LA22 or Erbitux were prepared, and in
      vitro cytotoxicity assays with A549 cells showed that LA22-MMC was much more
      potent than Erbitux or Erbitux-MMC. Viabilities of A549 cells treated with LA22
      MMC, Erbitux or Erbitux-MMC were 35%, 94%, and 81%, respectively.
      Immunoscintigraphy of xenografts of human A431 and A549 cells in nude mice both
      showed that (125)I-labeled-LA22-MMC enriched in tumor sites prominently. Most
      importantly, in vivo assays showed LA22-MMC was significantly more effective than
      free drug MMC in the treatment of subcutaneous xenografts of human A431 cells in
      nude mice (83% inhibition for LA22-MMC and 30% for MMC). We concluded that LA22
      MMC could be a very potent drug for treatment of solid tumors.

PMID- 16950202
TI  - TRAIL-induced cleavage and inactivation of SPAK sensitizes cells to apoptosis.
AB  - Ste20-related proline-alanine-rich kinase (SPAK) has been linked to various
      cellular processes, including proliferation, differentiation, and ion transport
      regulation. Recently, we showed that SPAK mediates signaling by the TNF receptor,
      RELT. The presence of a caspase cleavage site in SPAK prompted us to study its
      involvement in apoptotic signaling induced by another TNF member, TRAIL. We show
      that TRAIL stimulated caspase 3-like proteases that cleaved SPAK at two distinct
      sites. Cleavage had little effect on the activity of SPAK but removed its
      substrate-binding domain. In addition, TRAIL reduced the activity of SPAK in HeLa
      cells in a caspase-independent manner. Thus, TRAIL inhibited SPAK by two
      mechanisms: activation of caspases, which removed its substrate-binding domain,
      and caspase-independent down-regulation of SPAK activity. Furthermore, reducing
      the amount of SPAK by siRNA increased the sensitivity of HeLa cells to TRAIL
      induced apoptosis. Thus, TRAIL down-regulation of SPAK is an important event that
      enhances its apoptotic effects.

PMID- 16950203
TI  - The physiological role of CTGF/CCN2 in zebrafish notochond development and
      biological analysis of the proximal promoter region.
AB  - During mouse embryogenesis, CTGF/CCN2 is expressed in zones containing
      hypertrophic chondroctyes and calcifying cartilage such as long bones, ribs,
      vertebral column, and phalanges. But in fish, its expression is yet unclear.
      Development of the vertebrae is morphologically similar among vertebrates,
      indicating that the underlying mechanism regulating the process is highly
      conserved during evolution. Analysis of 3.2kb of the CTGF/CCN2 proximal promoter
      sequence revealed a consensus TATAA box, putative AP1, Brn-2, CdxA, C/EBP alpha,
      C/EBP beta, C-Ets-, delta E, HFH-2, and HSF2 binding sites. Transient expression
      experiments with a 5'-deletion revealed at least 4 regulatory regions in the
      zebrafish CTGF/CCN2 gene, 2 with a stimulatory effect on transcription and 2 with
      an apparent inhibitory effect after IGF-I treatment in the ZFL cell line. To
      study the promoter-specific expression, we constructed a series of CTGF/CCN2 (3.0
      , 2.5-, 2.0-, 1.5-, 1.0-, and 0.4-kb) promoter-driven green fluorescent protein
      (GFP) fragments encoding the GFP cDNA transgene which was microinjected into
      zebrafish embryos. Morphological studies of transgenic zebrafish indicated that
      the CTGF/CCN2 promoter-driven GFP transcripts appeared in the notochord. Targeted
      knockdown of the CTGF/CCN2 gene by two antisense morpholino oligonucleotides
      resulted in disruptions to notochord development. From a comparative point of
      view, this study of the CTGF/CCN2 gene in zebrafish may correlate well with those
      previously published on the mouse. These molecular results suggest that CTGF/CCN2
      plays an important role in notochord development and is required for general
      embryonic development.

PMID- 16950204
TI  - Biphasic activation of liver regeneration-associated signals in an early stage
      after portal vein branch ligation.
AB  - At an early stage in liver regeneration, a variety of factors including
      transcriptional factors, proinflammatory cytokines, and proto-oncogenes are
      activated or expressed. However, these responses are affected by surgical stress
      in the conventional portal vein branch ligation model (PVL). We sought to
      determine the net activation of early regeneration-associated signals after PVL
      using a newly developed non-surgical stress PVL model. Male Wistar rats were
      assigned into two groups, a stress-PVL (sPVL) model with laparotomy and portal
      vein branch ligation, and a non-stress-PVL (nsPVL) one subjected to portal vein
      branch ligation 1 week after laparotomy in which the effects of surgical stress
      were subsided. The activation of transcriptional factors and expression of
      immediate early genes were analyzed at an early time point (within 24 h) by
      Western blotting and RT-PCR, respectively. A monophasic upregulation of nuclear
      factor-kappaB (NF-kappaB) and phosphorylated-signal transducer and activator of
      transcription 3 (p-STAT3) peaked at 3h after sPVL was observed. In contrast, the
      expression pattern of these factors was biphasic (first peak at 0.5-1 h, second
      peak at 3-6 h) in nsPVL group. The expression pattern of immediate early genes
      showed a similar trend between sPVL and nsPVL. cDNA array analysis for the non
      ligated lobe at 2 h after PVL revealed a much higher gene activation in sPVL than
      in nsPVL. These results indicate that previously observed activation pattern of
      regeneration-associated signals after PVL is significantly affected by the effect
      of laparotomy and our results using nsPVL model may more accurately represent
      liver regeneration-associated signal pattern.

PMID- 16950205
TI  - Cloning, embryonic expression, and functional characterization of two novel
      connexins from Xenopus laevis.
AB  - Vertebrate gap junctions are constituted of connexin (Cx) proteins. In Xenopus
      laevis, only seven different Cxs have been described so far. Here, we identify
      two new Cxs from X. laevis. Cx28.6 displays > 60% amino acid identity with human
      Cx25, Cx29 displays strong homology with mouse Cx26 and Cx30. Cx29 is expressed
      throughout embryonic development. Cx28.6 mRNA is only transiently found from
      stage 22 to 26 of development. While no Cx28.6 expression could be detected by
      whole mount in situ hybridization, expression of Cx29 was found in the developing
      endoderm, lateral mesoderm, liver anlage, pronephros, and proctodeum. Ectopic
      expression of Cx28.6 failed to produce functional gap-junctions. In contrast,
      ectopic expression of full-length Cx29 in HEK293 and COS-7 cells resulted in the
      formation of gap junction-like structures at the cell-cell interfaces. Ectopic
      expression of Cx29 in communication deficient N2A cell pairs led to functional
      electrical coupling.

PMID- 16950206
TI  - Dividing roles of prion protein in staurosporine-mediated apoptosis.
AB  - Prion protein (PrPC) is a normal cellular glycoprotein that is expressed in
      almost all tissues including the central nervous system. Much attention has been
      focused on this protein because conversion of the normal PrPC to the diseased
      form (PrPSc) plays an essential role in transmissible spongiform encephalopathies
      such as mad cow disease and Creutzfeldt-Jakob disease. In spite of the extensive
      effort, the normal physiological function of PrPC remains elusive. Emerging
      evidence suggests that PrPC plays a protective role against cellular stresses
      including apoptosis induced by various pro-apoptotic agents such as Bax and
      staurosporine (STS), however, other reports showed overexpression of PrPC
      enhances STS-mediated apoptosis. In this study, we took a different approach by
      depleting endogenous PrPC using specific interfering RNA technique and compared
      the depleting and overproducing effects of PrPC on STS-induced apoptosis in neuro
      2a (N2a) cells. We demonstrate here that down-regulation of PrPC sensitizes N2a
      cells to STS-induced cytotoxicity and apoptosis. The enhanced apoptosis induced
      by STS was shown by increased DNA fragmentation, immunoreactivity of Bax, and
      caspase-3 cleavage. We also showed that overproduction of PrPC had little or no
      effect on STS-mediated DNA fragmentation in N2a cells but it augments STS
      mediated apoptosis in HEK293 cells, suggesting a cell line-specific effect. In
      addition, the inhibitory effect of PrPC on STS-mediated cellular stress appears
      to be modulated in part through induction of cell cycle G2 accumulation.
      Together, our data suggest that physiological level of endogenous PrPC plays a
      protective role against STS-mediated cellular stress. Loss of this protection
      could render cells more prone to cellular insults such as STS.

PMID- 16950207
TI  - Synergistic induction of apoptosis by sulindac and arsenic trioxide in human lung
      cancer A549 cells via reactive oxygen species-dependent down-regulation of
      survivin.
AB  - Survivin, a member of the inhibitor of apoptosis protein (IAP) family, may be a
      good target for cancer therapy because it is expressed in a variety of human
      tumors but not in differentiated adult tissues. In the present study, we show
      that a combination of sulindac and arsenic trioxide (ATO) induces more extensive
      apoptosis than either drug alone in A549 human non-small cell lung carcinoma
      (NSCLC) cells. Treatment with sulindac/ATO reduced the expression of survivin and
      promoted major apoptotic signaling events, namely, collapse of the mitochondrial
      membrane potential, release of cytochrome c, and activation of caspases. Combined
      sulindac/ATO treatment did not significantly affect the levels of other members
      of the IAP family (XIAP, cIAP1 and cIAP2), indicating that the effects were
      specific to survivin. In addition, sulindac/ATO treatment induced the production
      of reactive oxygen species and the antioxidant N-acetyl-l-cysteine blocked the
      down-regulation of survivin and induction of apoptotic signaling by the
      combination of sulindac and ATO. Combined sulindac/ATO treatment also activated
      p53 expression, and inhibition of p53 expression by small interfering RNA (siRNA)
      prevented sulindac/ATO-induced down-regulation of survivin, suggesting that
      survivin expression is negatively regulated by p53. Overexpression of survivin
      reduced sulindac/ATO-induced apoptosis in A549 cells and reduction of survivin
      levels by siRNA sensitized the cells to sulindac/ATO-induced cell death. These
      results demonstrate that, in A549 human NSCLC cells, sulindac/ATO-induced
      apoptosis is mediated by the reactive oxygen species-dependent down-regulation of
      survivin.

PMID- 16950208
TI  - Blockade of AKT activation in prostate cancer cells with a small molecule
      inhibitor, 9-chloro-2-methylellipticinium acetate (CMEP).
AB  - AKT inhibitors are potentially promising drug candidates for the treatment of
      cancer. The inhibitory effects of a potent and selective AKT/BKB small molecule
      inhibitor, 9-chloro-2-methylellipticinium acetate (CMEP), on the activation of
      AKT, its antiproliferation and apoptosis-inducing effects in prostate cancer cell
      lines: DU-145, PC-3, LNCaP, and CL-1, an androgen-independent LNCaP variant, and
      CL-1 xenograft mouse model were assessed by Western blot analysis, kinase assay,
      cell survival assay, and apoptosis assay in this report. It has been observed
      that the expression levels of AKT1, AKT2, and AKT3 vary, but the levels of
      phospho-Ser473 AKT and phospho-Thr308 AKT are quite unique in these cancer cell
      lines, and that CL-1 cells have the highest basal levels of AKT activation among
      these cell lines. In PC-3 cells, CMEP has been found to inhibit only AKT
      activation at both normal and serum-starvation conditions, not to inhibit PI3K,
      PDK1, or MAPK. More importantly, it has been discovered that CMEP inhibits cell
      proliferation, and induces apoptosis in prostate cancer cells which have high
      levels of AKT activation and lack PTEN or harbor PTEN mutation, such as CL-1,
      LNCaP, and PC-3; only shows a minimal activity in DU-145 cancer cells which do
      not have AKT activation. Furthermore, it has been demonstrated that CMEP
      treatment inhibits phospho-Ser473 AKT and phospho-p70S6K while stimulating TSC2
      in the tumor tissue from CL-1-bearing mice. In conclusion, by specific blockade
      of the activation of AKT, CMEP preferentially inhibits growth and induces
      apoptosis in prostate cancer cells which have high-levels of AKT activation.

PMID- 16950209
TI  - Genetic and environmental contributions underlying stability in childhood
      obsessive-compulsive behavior.
AB  - BACKGROUND: Little is known about the stability of obsessive-compulsive (OC)
      behavior during childhood. The objective of this study is to determine the
      developmental stability of pediatric OC behavior and the genetic and
      environmental influences on stability in a large population-based twin sample.
      METHODS: Maternal and paternal ratings on the 8-item Obsessive Compulsive Scale
      of the Child Behavior Checklist (CBCL-OCS) on Dutch mono- and dizygotic twin
      pairs from 8083 families were collected at ages 7, 10, and 12 years. Using a
      longitudinal twin design, stability of OC behavior and genetic and environmental
      influences on stability were determined. Using cutoff criteria, persistent,
      resilient, and new onset cases were identified in this sample. RESULTS: OC
      behavior assessed by the CBCL-OCS showed a moderate stability with phenotypic
      correlations of around .50 for boys and for girls. Stability of OC behavior was
      influenced by genetic factors, by environmental factors shared by children
      growing up in the same family, and by non-shared environmental factors. Stability
      for OCS was lower when categorical data were analyzed than when quantitative
      definitions were used. CONCLUSIONS: OC behavior is moderately stable in
      childhood. Stability of OC behavior is influenced by genetic, shared, and non
      shared environmental factors.

PMID- 16950210
TI  - Buprenorphine duration of action: mu-opioid receptor availability and
      pharmacokinetic and behavioral indices.
AB  - BACKGROUND: Buprenorphine (BUP) is effective in the treatment of opioid
      dependence when given on alternating days, probably as a result of long-lasting
      occupation of micro opioid receptors (microORs). This study examined the duration
      of action of BUP at microORs and correlations with pharmacokinetic and
      pharmacodynamic outcomes in 10 heroin-dependent volunteers. METHODS: Availability
      of microOR (measured with positron emission tomography and [(11)C]-carfentanil),
      plasma BUP concentration, opioid withdrawal symptoms, and blockade of
      hydromorphone (HYD; heroin-like agonist) effects were measured at 4, 28, 52, and
      76 hours after omitting the 16 mg/d dose of BUP in a study reported elsewhere.
      RESULTS: Relative to heroin-dependent volunteers maintained on BUP placebo, whole
      brain microOR availability was 30%, 54%, 67%, and 82% at 4, 28, 52, and 76 hours
      after BUP. Regions of interest showed similar effects. Plasma concentrations of
      BUP were time dependent, as were withdrawal symptoms, carbon dioxide sensitivity
      and extent of HYD blockade. Availability of microOR was also correlated with BUP
      plasma concentration, withdrawal symptoms, and HYD blockade. CONCLUSIONS:
      Together with our previous findings, it appears that microOR availability
      predicts changes in pharmacokinetic and pharmacodynamic measures and that about
      50%-60% BUP occupancy is required for adequate withdrawal symptom suppression (in
      the absence of other opioids) and HYD blockade.

PMID- 16950211
TI  - Does the Child Behavior Checklist juvenile bipolar disorder phenotype identify
      bipolar disorder?
AB  - BACKGROUND: A profile of Child Behavior Checklist(CBCL) T-scores>or=70 on the
      attention problems, aggression, and anxious/depressed subscales has been proposed
      to identify juvenile bipolar disorder(JBD). We tested this hypothesis in a
      population-based sample. METHODS: Data for this analysis come from a birth
      records-based twin sample having semi-structured interview and CBCL data
      (N=1,346). We compared prevalence of DSM-IV psychiatric disorders and suicidal
      behaviors in CBCL-JBD and non-CBCL-JBD subjects. Twin modeling assessed genetic
      and environmental contributions to CBCL-JBD. Associations with DRD4 and DAT1 were
      examined using chi-square tests. RESULTS: The prevalence of CBCL-JBD was 2.5%. No
      subjects with CBCL-JBD met criteria for bipolar or other mood disorders. CBCL-JBD
      subjects had more oppositional defiant disorder (ODD), conduct disorder(CD), and
      attention deficit hyperactivity disorder(ADHD). The CBCL-JBD profile was uncommon
      in these disorders. CBCL-JBD subjects more frequently endorsed suicidal
      behaviors. The CBCL-JBD profile was heritable and associated with the number of
      DAT1 9-repeat 3' untranslated region alleles. CONCLUSIONS: The CBCL-JBD phenotype
      does not correspond with a semi-structured interview assessment of JBD. ADHD, CD,
      and ODD are common in children with CBCL-JBD but do not account for the profile.
      Increased suicidal behaviors indicate substantial impairment in CBCL-JBD
      subjects.

PMID- 16950212
TI  - Caudate nucleus volume and cognitive performance: Are they related in childhood
      psychopathology?
AB  - BACKGROUND: Impaired neuropsychological test performance, especially on tests of
      executive function and attention, is often seen in children diagnosed with autism
      spectrum disorders (ASD). Structures involved in fronto-striatal circuitry, such
      as the caudate nucleus, may support these cognitive abilities. However, few
      studies have examined caudate volumes specifically in children with ASD, or
      correlated caudate volumes to cognitive ability. METHODS: Neuropsychological test
      scores and caudate volumes of children with ASD were compared to those of
      children with bipolar disorder (BD) and of typically developing (TD) children.
      The relationship between test performance and caudate volumes was analyzed.
      RESULTS: The ASD group displayed larger right and left caudate volumes, and
      modest executive deficits, compared to TD controls. While caudate volume
      inversely predicted performance on the Wisconsin Card Sorting Test in all
      participants, it differentially predicted performance on measures of attention
      across the ASD, BD and TD groups. CONCLUSIONS: Larger caudate volumes were
      related to impaired problem solving. On a test of attention, larger left caudate
      volumes predicted increased impulsivity and more omission errors in the ASD group
      as compared to the TD group, however smaller volume predicted poorer discriminant
      responding as compared to the BD group.

PMID- 16950213
TI  - Attention-deficit/hyperactivity disorder and comorbid disruptive behavior
      disorders: evidence of pleiotropy and new susceptibility loci.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) comorbid with
      oppositional defiant disorder (ODD) or conduct disorder (CD) and substance
      abuse/dependence seems to represent a specific subset within the phenotypic ADHD
      spectrum. METHODS: We applied complex segregation and linkage analyses in a set
      of multigenerational families densely segregating ADHD comorbid with ODD, CD,
      alcohol abuse/dependence, and nicotine dependence. RESULTS: Our data suggest that
      ADHD cosegregates with disruptive behaviors as a unique, phenotypically variable
      trait as evidenced by highly significant pair-wise linkages among: ADHD and ODD
      (logarithm of odds [LOD]=14.19), ADHD and CD (LOD=5.34), ODD and CD (LOD=6.68),
      and CD and alcohol abuse/dependence (LOD=3.98). In addition to previously
      reported ADHD susceptibility loci, we found evidence of linkage for comorbid ADHD
      phenotypes to loci at 8q24, 2p21-22.3, 5p13.1-p13.3, 12p11.23-13.3, 8q15, and
      14q21.1-22.2. These results were replicated with an affected status phenotype
      derived from latent class clusters. CONCLUSIONS: Patterns of cosegregation of
      ADHD with comorbidities can inform our understanding of the inheritance patterns
      not only of ADHD but also of disruptive behavioral disorders and alcohol
      abuse/dependence. Refining the comorbid ADHD phenotype by determining the
      cosegregation profile of specific comorbidities might be a powerful tool for
      defining significant regions of linkage.

PMID- 16950214
TI  - Cortisol moderates the relationship between testosterone and aggression in
      delinquent male adolescents.
AB  - BACKGROUND: In animals, strong evidence exists for an association between
      testosterone and aggression. In humans, and particularly in children and
      adolescents, findings have been less consistent. Previous research has suggested
      that this may partly be due to moderating effects of other factors, e.g.,
      hormones. This study aims to investigate the moderating effect of cortisol on the
      relationship between testosterone and subtypes of aggression in delinquent male
      adolescents. METHODS: Participants were 103 boys (mean age 13.7) referred to a
      delinquency diversion program. Testosterone and cortisol levels were determined
      from saliva samples collected during resting conditions and related to self
      report scores on overt and covert aggression. RESULTS: Linear regression analyses
      revealed a significant interaction between cortisol and testosterone in relation
      to overt aggression, with a significant positive relationship between
      testosterone and overt aggression in subjects with low cortisol levels but not in
      subjects with high cortisol levels. Using the same model for covert aggression,
      no significant effects of testosterone, cortisol, or testosterone x cortisol
      interaction were found. CONCLUSIONS: These results indicate a moderating effect
      of cortisol on the relationship between testosterone and overt aggression in
      delinquent male adolescents. Implications and directions for future research are
      discussed.

PMID- 16950215
TI  - D2 antidopaminergic modulation of frontal lobe function in healthy human
      subjects.
AB  - BACKGROUND: Although the major principles of dopamine (DA) signaling have been
      well described previously, its precise modulatory impact on the prefrontal cortex
      (PFC) in humans is poorly understood. Two major neurophysiological models propose
      segregated functional circuits on the systems level as well as D(1) and D(2)
      receptor-dependent processing states on the cellular level (two-state model).
      METHODS: We examined the predictive validity of these models in 10 healthy male
      volunteers with a haloperidol challenge (HLP). Cortico-striatal-thalamo-cortical
      (CSTC) motor loop functions were examined during functional magnetic resonance
      imaging (fMRI) with a sequential finger opposition task. Neuropsychological
      implications of the two-state model were evaluated with a test battery of D(1)-
      or D(2)-sensitive prefrontal measures. RESULTS: Analysis of fMRI data revealed a
      significant HLP-induced blood oxygen level dependent-signal decrease in the
      sensorimotor striatum and a lateralized activation loss of ipsilateral higher
      order motor cortices and contralateral cerebellum. Neuropsychological evaluation
      demonstrated a preferential impairment of D(2)-sensitive functions, whereas D(1)
      or non-dopaminergic domains were unaffected. CONCLUSIONS: Our data support the
      hypothesis that mesocortical D(1) and D(2) receptors exert differential
      influences in the PFC for cognitive function, but the nigrostriatal CSTC network
      model for the motor domain could not be confirmed.

PMID- 16950216
TI  - Context conditioning and behavioral avoidance in a virtual reality environment:
      effect of predictability.
AB  - BACKGROUND: Sustained anxiety can be modeled using context conditioning, which
      can be studied in a virtual reality environment. Unpredictable stressors increase
      context conditioning in animals. This study examined context conditioning to
      predictable and unpredictable shocks in humans using behavioral avoidance,
      potentiated startle, and subjective reports of anxiety. METHODS: Subjects were
      guided through three virtual rooms (no-shock, predictable, unpredictable
      contexts). Eight-sec duration colored lights served as conditioned stimuli (CS).
      During acquisition, no shock was administered in the no-shock context. Shocks
      were paired with the CS in the predictable context and were administered randomly
      in the unpredictable context. No shock was administered during extinction.
      Startle stimuli were delivered during CS and between CS to assess cued and
      context conditioning, respectively. To assess avoidance, subjects freely
      navigated into two of the three contexts to retrieve money. RESULTS: Startle
      between CS was potentiated in the unpredictable context compared to the two other
      contexts. Following acquisition, subjects showed a strong preference for the no
      shock context and avoidance of the unpredictable context. CONCLUSIONS: Consistent
      with animal data, context conditioning is increased by unpredictability. These
      data support virtual reality as a tool to extend research on physiological and
      behavioral signs of fear and anxiety in humans.

PMID- 16950217
TI  - Meta-analysis of structural imaging findings in attention-deficit/hyperactivity
      disorder.
AB  - BACKGROUND: Although there are many structural neuroimaging studies of attention
      deficit/hyperactivity disorder (ADHD) in children, there are inconsistencies
      across studies and no consensus regarding which brain regions show the most
      robust area or volumetric reductions relative to control subjects. Our goal was
      to statistically analyze structural imaging data via a meta-analysis to help
      resolve these issues. METHODS: We searched the MEDLINE and PsycINFO databases
      through January 2005. Studies must have been written in English, used magnetic
      resonance imaging, and presented the means and standard deviations of regions
      assessed. Data were extracted by one of the authors and verified independently by
      another author. RESULTS: Analyses were performed using STATA with metan,
      metabias, and metainf programs. A meta-analysis including all regions across all
      studies indicated global reductions for ADHD subjects compared with control
      subjects, standardized mean difference=.408, p<.001. Regions most frequently
      assessed and showing the largest differences included cerebellar regions, the
      splenium of the corpus callosum, total and right cerebral volume, and right
      caudate. Several frontal regions assessed in only two studies also showed large
      significant differences. CONCLUSIONS: This meta-analysis provides a quantitative
      analysis of neuroanatomical abnormalities in ADHD and information that can be
      used to guide future studies.

PMID- 16950218
TI  - Alterations in medial prefrontal cortical activity and plasticity in rats with
      disruption of cortical development.
AB  - BACKGROUND: Psychiatric disorders such as schizophrenia are believed to emerge
      from an interaction of several factors. Thus, a genetic predisposition can lead
      to developmental compromises that may leave the system more susceptible to
      deficits induced by subsequent environmental variables such as stress. METHODS:
      The impact of neurodevelopmental interruption induced by exposure of rats
      prenatally to a compound methylazoxymethanol acetate (MAM) that disrupts neuronal
      proliferation was investigated using in vivo electrophysiologic recordings from
      the prefrontal cortex of adult rats. RESULTS: Prenatal exposure to MAM resulted
      in alterations in the medial prefrontal cortex indicative of a compromise in
      information processing. Specifically, we observed a disruption in activity
      patterns consistent with deficits in neuronal synchronization and abnormal
      augmentation of synaptic plasticity that was more severely disrupted by stress
      exposure than in normal animals. Furthermore, these deficits could be reversed by
      manipulating the mesocortical dopamine system. CONCLUSIONS: These results suggest
      that disruption of early cortical development causes impairments in medial
      prefrontal cortical function at adulthood that are more vulnerable to disruptive
      influences, despite the presence of only subtle structural alterations in the
      brain.

PMID- 16950220
TI  - Symptom provocation in specific phobia affects the substance P neurokinin-1
      receptor system.
AB  - BACKGROUND: Animal studies demonstrate that stress and negative affect enhance
      the release of the neuropeptide substance P (SP), which binds to the neurokinin 1
      (NK1) receptor. This positron emission tomography (PET) study evaluated how the
      activity in the SP-NK1 receptor system in the amygdala was affected by fear
      provocation in subjects with specific phobia. METHODS: Sixteen adult women with
      DSM-IV-defined specific phobia for either snakes or spiders but not both viewed
      pictures of feared and non-feared animals while being PET-scanned for 60 min with
      the highly specific NK1 receptor antagonist [(11)C]GR205171 as the labeled PET
      tracer. RESULTS: The uptake of the labeled NK1 receptor antagonist was
      significantly reduced in the right amygdala during phobic stimulation. In the
      left amygdala no significant differences were found between phobic and non-phobic
      conditions. There was a negative correlation in the right, but not left, amygdala
      between subjective anxiety ratings and NK1 tracer binding. CONCLUSIONS: Fear
      provocation affects the SP-NK1 receptor system in the right amygdala. This
      reflects reduced NK1 receptor availability during fear and could mirror an
      increased release of endogenous substance P.

PMID- 16950221
TI  - The effects of guanfacine on context processing abnormalities in schizotypal
      personality disorder.
AB  - BACKGROUND: The signature of impaired cognition in people with schizotypal
      personality disorder (SPD) may be centrally related to working memory
      impairments. Guanfacine, an alpha2A agonist that acts post-synaptically in the
      prefrontal cortex (PFC), has shown potential for reducing working memory
      limitations in other populations. This study examined the potential of guanfacine
      for improving context processing, a feature of working memory, in SPD. METHODS:
      29 individuals with SPD entered into a 4-week, randomized parallel-design, double
      blind, placebo-controlled trial of guanfacine treatment, followed by a 4-week
      open-label extension. A modified version of the AX-Continuous Performance Test
      (AX-CPT) was administered. On this task, evidence of intact context processing
      includes few BX errors (false cue, correct probe) and higher levels of AY errors
      (correct cue, false probe). RESULTS: At the end of double-blind treatment,
      participants treated with guanfacine demonstrated a significant reduction in BX
      errors and a small but significant increase in AY errors, a pattern that was not
      seen in the participants treated with placebo. CONCLUSIONS: SPD participants
      improved in their context processing toward a normal response bias, making fewer
      BX and more AY errors, after being treated with guanfacine.

PMID- 16950222
TI  - Prefrontal-hippocampal coupling during memory processing is modulated by COMT
      val158met genotype.
AB  - BACKGROUND: Studies in humans and in animals have demonstrated that a network of
      brain regions is involved in performance of declarative and recognition memory
      tasks. This network includes the hippocampal formation (HF) as well as the
      ventrolateral prefrontal cortex (VLPFC). Studies in animals have suggested that
      the relationship between these brain regions is strongly modulated by dopamine.
      METHODS: Using fMRI in healthy humans matched for a series of demographic and
      genetic variables, we studied the effect of the COMT val158met polymorphism on
      function of HF and VLPFC as well as on their functional coupling during
      recognition memory. RESULTS: The COMT Val allele was associated with: relatively
      poorer performance at retrieval; reduced recruitment of neuronal resources in HF
      and increased recruitment in VLPFC during both encoding and retrieval; and
      unfavorable functional coupling between these two regions at retrieval. Moreover,
      functional coupling during retrieval was predictive of behavioral accuracy.
      CONCLUSIONS: These results shed new light on individual differences in
      responsivity and connectivity between HF and VLPFC related to genetic modulation
      of dopamine, a mechanism accounting at least in part for individual differences
      in recognition memory performance.

PMID- 16950219
TI  - Parvalbumin neurons in the entorhinal cortex of subjects diagnosed with bipolar
      disorder or schizophrenia.
AB  - BACKGROUND: Growing evidence indicates that the entorhinal cortex (ECx) might be
      affected in schizophrenia (SZ) and bipolar disorder (BD). To test whether
      distinct interneuronal subpopulations might be altered, numbers of parvalbumin
      immunoreactive (PVB-IR) neurons were measured in the ECx of BD and SZ subjects.
      These neurons play a pivotal role within ECx intrinsic circuits. METHODS:
      Numbers, numerical density, and soma size of PVB-IR neurons were measured in the
      ECx of normal control (n = 16), BD (n = 10), and SZ (n = 10) subjects. The volume
      of the ECx was measured in Nissl-stained sections. RESULTS: In BD, decreases of
      total numbers (p = .02) and numerical densities (p = .01) of PVB-IR neurons were
      detected in the ECx. Within distinct subregions, reductions were detected in the
      superficial layers of the lateral (p = .02), intermediate (p = .04), and caudal
      (p = .01) ECx. In SZ, total numbers and numerical densities were not altered. A
      reduction of soma size was present in the intermediate ECx (p = .01). Volume was
      unaffected in either disorder. CONCLUSIONS: In BD, a decrease of PVB-IR neurons
      may alter intrinsic inhibitory networks within the superficial layers of the ECx.
      The likely consequence is a disruption of integration and transfer of information
      from the cerebral cortex to the hippocampus.

PMID- 16950223
TI  - Amygdala reactivity and mood-congruent memory in individuals at risk for
      depressive relapse.
AB  - BACKGROUND: According to cognitive diathesis-stress theories, a latent cognitive
      vulnerability to depression is activated by negative affect in individuals at
      risk for depressive relapse. This vulnerability can manifest as mood-congruent
      memory during sad mood and may involve amygdala response, which is implicated in
      memory for emotionally arousing stimuli. This study examined whether amygdala
      modulates memory for negatively valenced words before and after a sad mood
      induction in healthy individuals with and without a history of recurrent major
      depression. METHODS: Fourteen unmedicated remitted depressed (RD) and 14 matched
      never depressed (ND) individuals were scanned using functional magnetic resonance
      imaging (fMRI) while performing a self-referent encoding/evaluation task (SRET)
      preceding and following a sad mood challenge. After each SRET, participants' free
      recall was assessed. RESULTS: Following sad mood induction, bilateral amygdala
      response during encoding of valenced words predicted increased recall of negative
      self-referent words for a subset of RD participants. This association was not
      present before the sad mood induction and was not evident in individuals without
      a history of depression, regardless of mood state. CONCLUSIONS: These results are
      consistent with cognitive diathesis-stress theories and suggest a role for the
      amygdala in modulating mood-congruent memory during transient sad mood in
      individuals who are vulnerable to depression relapse.

PMID- 16950224
TI  - RETRACTED: Elaborative Verbal Encoding and Altered Anterior Parahippocampal
      Activation in Adolescents and Young Adults at Genetic Risk for Schizophrenia
      Using fMRI.
AB  - This article has been retracted, consistent with Elsevier Policy on Article
      Withdrawal. Please see . The Publisher apologises for any inconvenience this may
      cause.

PMID- 16950226
TI  - Enhanced preproenkephalin-B-derived opioid transmission in striatum and
      subthalamic nucleus converges upon globus pallidus internalis in L-3,4
      dihydroxyphenylalanine-induced dyskinesia.
AB  - BACKGROUND: A role for enhanced opioid peptide transmission has been suggested in
      the genesis of levodopa-induced dyskinesia. However, basal ganglia nuclei other
      than the striatum have not been regarded as potential sources, and the opioid
      precursors have never been quantified simultaneously with the levels of opioid
      receptors at the peak of dyskinesia severity. METHODS: The levels of messenger
      RNA (mRNA) encoding the opioid precursors preproenkephalin-A and preproenkephalin
      B in the striatum and the subthalamic nucleus and the levels of mu, delta, and
      kappa opioid receptors were measured within the basal ganglia of four groups of
      nonhuman primates killed at the peak of effect: normal, parkinsonian,
      parkinsonian chronically-treated with levodopa without exhibiting dyskinesia, and
      parkinsonian chronically-treated with levodopa showing overt dyskinesia. RESULTS:
      Dyskinesia are associated with reduction in opioid receptor binding and
      specifically of kappa and mu receptor binding in the globus pallidus internalis
      (GPi), the main output structure of the basal ganglia. This decrease was
      correlated with enhancement of the expression of preproenkephalin-B mRNA but not
      that of preproenkephalin-A in the striatum and the subthalamic nucleus.
      CONCLUSIONS: Abnormal transmission of preproenkephalin-B-derived opioid coming
      from the striatum and the subthalamic nucleus converges upon GPi at the peak of
      dose to induce levodopa-induced dyskinesia.

PMID- 16950225
TI  - Children and adolescents with autism exhibit reduced MEG steady-state gamma
      responses.
AB  - BACKGROUND: Recent neuroimaging studies of autism have indicated reduced
      functional connectivity during both cognitive tasks and rest. These data suggest
      long-range connectivity may be compromised in this disorder, and current
      neurological theories of autism contend disrupted inter-regional interactions may
      be an underlying mechanism explaining behavioral symptomatology. However, it is
      unclear whether deficient neuronal communication is attributable to fewer long
      range tracts or more of a local deficit in neural circuitry. This study examines
      the integrity of local circuitry by focusing on gamma band activity in auditory
      cortices of children and adolescents with autism. METHODS: Ten children and
      adolescents with autism and 10 matched controls participated. Both groups
      listened to 500 ms duration monaural click trains with a 25 ms inter-click
      interval, as magnetoencephalography was acquired from the contralateral
      hemisphere. To estimate 40 Hz spectral power density, we performed time-frequency
      decomposition of the single-trial magnetic steady-state response data using
      complex demodulation. RESULTS: Children and adolescents with autism exhibited
      significantly reduced left hemispheric 40 Hz power from 200-500 ms post-stimulus
      onset. In contrast, no significant between group differences were observed for
      right hemispheric cortices. CONCLUSIONS: The production and/or maintenance of
      left hemispheric gamma oscillations appeared abnormal in participants with
      autism. We interpret these data as indicating that in autism, particular brain
      regions may be unable to generate the high-frequency activity likely necessary
      for binding and other forms of inter-regional interactions. These findings
      augment connectivity theories of autism with novel evidence that aberrations in
      local circuitry could underlie putative deficiencies in long-range neural
      communication.

PMID- 16950227
TI  - Regarding "Increased prefrontal and hippocampal glutamate concentration in
      schizophrenia: evidence from a magnetic resonance spectroscopy study".

PMID- 16950228
TI  - Ventral striatal hyporesponsiveness during reward anticipation in attention
      deficit/hyperactivity disorder.
AB  - BACKGROUND: Although abnormalities in reward processing have been proposed to
      underlie attention-deficit/hyperactivity disorder (ADHD), this link has not been
      tested explicitly with neural probes. METHODS: This hypothesis was tested by
      using fMRI to compare neural activity within the striatum in individuals with
      ADHD and healthy controls during a reward-anticipation task that has been shown
      previously to produce reliable increases in ventral striatum activity in healthy
      adults and healthy adolescents. Eleven adolescents with ADHD (5 off medication
      and 6 medication-naive) and 11 healthy controls (ages 12-17 y) were included.
      Groups were matched for age, gender, and intelligence quotient. RESULTS: We found
      reduced ventral striatal activation in adolescents with ADHD during reward
      anticipation, relative to healthy controls. Moreover, ventral striatal activation
      was negatively correlated with parent-rated hyperactive/impulsive symptoms across
      the entire sample. CONCLUSIONS: These findings provide neural evidence that
      symptoms of ADHD, and impulsivity or hyperactivity in particular, may involve
      diminished reward anticipation, in addition to commonly observed executive
      dysfunction.

PMID- 16950229
TI  - Cortisol and adrenocorticotropic hormone responses to naloxone in subjects with
      high and low neuroticism.
AB  - BACKGROUND: Neuroticism is a highly heritable personality trait that is a risk
      factor for certain affective and anxiety disorders. Studies link neuroticism with
      alterations in the Hypothalamic-Pituitary-Adrenal (HPA) stress response. We
      interrogated HPA axis dynamics as a function of neuroticism, employing the opioid
      receptor antagonist, naloxone. METHODS: Subjects were assigned to either high or
      low neuroticism groups on the basis of Revised Neuroticism, Extraversion,
      Openness Personality Inventory (NEO-PI-R) scores and received naloxone
      hydrochloride (0, 125 microg/kg, and 375 microg/kg). Serum adrenocorticotropic
      hormone (ACTH) and cortisol levels were monitored. RESULTS: Significant, dose
      dependent differences in cortisol response were observed between neuroticism
      groups, whereas no differences were observed in ACTH. The low neuroticism group
      demonstrated a dose-dependent cortisol response with a plateau at the 125
      microg/kg dose of naloxone. In contrast, the high neuroticism group demonstrated
      a graded cortisol response to all doses of naloxone. CONCLUSIONS: These findings
      show that neuroticism is associated with altered cortisol responses to opioid
      receptor blockade, suggesting that alterations in HPA axis function already exist
      in persons at increased risk for certain depressive and anxiety disorders.

PMID- 16950231
TI  - Examining the relationship between obsessive-compulsive disorder and attention
      deficit/hyperactivity disorder in children and adolescents: a familial risk
      analysis.
AB  - BACKGROUND: To use family study methodology to examine the relationship between
      obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder
      (ADHD) in children and adolescents. METHODS: We assessed for ADHD and OCD in the
      1533 first-degree relatives of three groups of index children: those with ADHD
      and OCD, those with ADHD but no OCD, and matched controls with neither disorder.
      RESULTS: The risk for ADHD was similarly elevated in families of ADHD youth with
      (18.9%) and without OCD (20.1%; p = .91), and both groups had significantly
      higher rates of ADHD compared with controls (4.6%; p < or = .001), which was
      consistent with previous research showing a strong familial risk for ADHD. The
      risk for OCD was significantly elevated only among relatives of youth with ADHD
      plus comorbid OCD (13.0%) compared with controls (.5%; p < or = .001) and was
      consistent with previous research showing a strong familial risk for OCD.
      Relatives affected with ADHD had a significantly elevated risk for OCD compared
      with relatives unaffected by ADHD (7.4% vs. 1.3%; p < .001), suggestive of co
      segregation between these disorders. There was no evidence of nonrandom mating
      between ADHD- and OCD-affected spouses. CONCLUSIONS: These results extend
      previously reported findings regarding the heritability of both ADHD and OCD and
      provide new evidence of a familial relationship between ADHD and pediatric OCD
      that best fits the hypothesis of a unique familial subtype.

PMID- 16950230
TI  - Longitudinal follow-up of reproductive and metabolic features of valproate
      associated polycystic ovarian syndrome features: A preliminary report.
AB  - BACKGROUND: In the Systematic Treatment Enhancement Program for Bipolar Disorder,
      we showed that valproate is associated with new-onset menstrual-cycle
      irregularities and hyperandrogenism in 10.5% of 86 women. We now determine
      whether polycystic ovarian syndrome (PCOS) features reverse on valproate
      discontinutation. METHODS: Women with valproate-associated PCOS and those at risk
      for PCOS (valproate use < or =6 months) were re-evaluated for PCOS. RESULTS:
      Follow-up (mean 17 months) assessments were completed in 14 women (5 with
      treatment-emergent PCOS, 9 on valproate < or =6-month). Of seven women who
      developed valproate-associated PCOS, PCOS reproductive features remitted in three
      of four discontinuing valproate and persisted in all 3 continuing valproate.
      Menstrual-cycle irregularities improved among valproate-discontinuers whose PCOS
      features remitted (p = 0.01). There was a trend toward lower serum testosterone
      (p = 0.06). Body-weight and polycystic ovarian morphology did not change.
      CONCLUSIONS: In the first longitudinal bipolar-disorder study of valproate
      associated PCOS, most valproate-discontinuers had improved reproductive features
      of PCOS despite static body-weight.

PMID- 16950232
TI  - GABRB2 association with schizophrenia: commonalities and differences between
      ethnic groups and clinical subtypes.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) and haplotypes in intron 8 of
      type A gamma-aminobutyric acid (GABA(A)) receptor beta2 subunit gene (GABRB2)
      were initially found to be associated with schizophrenia in Chinese. This finding
      was subjected to cross-validation in this study with Japanese (JP) and German
      Caucasian (GE) subjects. METHODS: Single nucleotide polymorphisms discovery and
      genotyping were carried out through resequencing of a 1839 base pair (bp) region
      in GABRB2. Tagging SNPs (tSNPs) were selected based on linkage disequilibrium
      (LD), combinations of which were analyzed with Bonferroni correction and
      permutation for disease association. Random resampling was applied to generate
      size- and gender-balanced cases and control subjects. RESULTS: Out of the 17 SNPs
      (9.2/kilobase [kb]) revealed, 6 were population-specific. Population variations
      in LD were observable, and at least two low LD points were identified in both
      populations. Although disease association at single SNP level was only shown in
      GE, strong association was demonstrated in both JP (p = .0002 - .0191) and GE (p
      = .0033 - .0410) subjects, centering on haplotypes containing rs1816072 and
      rs1816071. Among different clinical subtypes, the most significant association
      was exhibited by systematic schizophrenia. CONCLUSIONS: Cross-population
      validation of GABRB2 association with schizophrenia has been obtained with JP and
      GE subjects, with the genotype-disease correlations being strongest in systematic
      schizophrenia, the most severe subtype of the disease.

PMID- 16950234
TI  - Dopamine and monogamy.
AB  - Social attachments play a central role in human society. In fact, such
      attachments are so important that deficits in the ability to form meaningful
      social bonds are associated with a variety of psychological disorders. Although
      mother-infant bonding has been studied for many years, we only recently have
      begun to examine the processes that underlie social bonds between adults. Over
      the past decade, central dopamine has become a focus of such research, especially
      its role in pair bonding between mates in species that display monogamous life
      strategies. Neuroanatomical and pharmacological studies in rodents have firmly
      established central dopamine systems, especially the mesocorticolimbic dopamine
      circuitry, in the formation, expression, and maintenance of monogamous pair
      bonds. As this research has progressed, it has become apparent that there is
      considerable overlap between the processes that underlie pair bonding and those
      that mediate responses to abused substances. This suggests that social bonding
      and substance abuse each may affect the other. Herein we review the current state
      of knowledge of central dopamine involvement in pair bond formation, expression,
      and maintenance. We first describe the neuroanatomical substrate within which
      dopamine exerts its effects on social bonding. We then describe dopamine receptor
      subtype-specific influences on pair bonding and how dopamine receptor activation
      may interact with activation of other neurochemical systems. Finally, we describe
      possible interactions between social bonding and substance abuse.

PMID- 16950233
TI  - Clonidine depresses LTP of C-fiber evoked field potentials in spinal dorsal horn
      via NO-cGMP pathway.
AB  - Clonidine, a specific alpha2-adrenergic receptor agonist, has been found to be
      effective for the treatment of neuropathic pain, the mechanism underlying the
      effect is, however, not well understood. Here, the effect of clonidine on long
      term potentiation (LTP) of C-fiber evoked field potentials in spinal dorsal horn,
      which is a synaptic model of injury-induced hyperalgesia, was investigated. LTP
      of C-fiber evoked field potentials was recorded in the superficial layers of
      spinal dorsal horn in anesthetized adult Sprague-Dawley rats. Clonidine and other
      substances were applied locally at the recording spinal segments before or after
      LTP induction by tetanic stimulation. We found that (1) Clonidine completely
      blocked LTP induction, when applied 30 min before tetanic stimulation and
      depressed spinal LTP, when applied 30 min and 3 h after LTP induction. (2) The
      inhibitory effect of clonidine on spinal LTP had two phases: a fast phase lasting
      for about 3.5 h and a slow phase persisting for the rest time of experiments (up
      to 8 h after drug). (3) Spinal clonidine at low dose (10.7 micro g/100 micro l)
      depressed spinal LTP but not C-fiber baseline response and at higher dose (107
      micro g/100 micro l) depressed both of them. (4) Pretreatment with alpha2
      adrenergic receptor antagonist yohimbine completely blocked the inhibitory effect
      of clonidine. (5) Pretreatment with muscarinic receptor antagonist atropine,
      nitric oxide synthesis inhibitor l-NNA or cGMP inhibitor ODQ depressed the fast
      phase inhibition significantly and abolished the slow phase inhibition
      completely. These results suggest that clonidine may exert analgesic effect by
      depressing the synaptic plasticity in spinal dorsal horn, via activation of
      muscarinic receptor-NO-cGMP pathway.

PMID- 16950235
TI  - Phosphorylation of HSP27 and synthesis of 14-3-3epsilon are parallel responses to
      hyperosmotic stress in the hippocampus.
AB  - A stress-responsive, mitogen-activated protein kinase, p38, is activated by
      phosphorylation in response to adverse environmental insults. In the present
      study, the effects of hyperosmolarity on p38 activation and protein synthesis in
      the brain were examined. Hyperosmotic stress of rat brain slices, produced by
      addition of sorbitol to the incubation buffer, produced prolonged phosphorylation
      and activation of p38, most prominently in the hippocampus as compared to the
      cortex or cerebellum. In comparison, the prototypic mitogen-activated protein
      kinase, extracellular signal-regulated kinase, was transiently phosphorylated and
      another stress-activated protein kinase, c-Jun NH(2)-terminal kinase, was not
      phosphorylated above basal levels. Examination of downstream p38 signaling events
      revealed phosphorylation of the small heat shock protein 27 (HSP27) that was
      abolished by incubation with SB202190 [4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5
      (4-pyridyl)1H-imidazole], a p38 inhibitor. Concomitantly, hyperosmolarity
      diminished total levels of protein synthesis within hippocampal slices, as
      determined by incorporation of (35)S-labeled methionine/cysteine into protein
      during tissue incubation. However, synthesis of a 30-kDa protein, identified as
      14-3-3epsilon with mass spectrometry, increased in response to hyperosmolarity.
      The synthesis of 14-3-3epsilon was dose-dependently induced by increasingly
      hyperosmotic conditions in a p38-independent manner. We conclude from these
      results that 14-3-3epsilon synthesis and p38-mediated HSP27 phosphorylation in
      the hippocampus are parallel responses to the hyperosmotic environment.

PMID- 16950236
TI  - Detection of BBB disruption and hemorrhage by Gd-DTPA enhanced MRI after embolic
      stroke in rat.
AB  - Thrombolytic therapy with rtPA increases the risk of hemorrhagic transformation
      (HT) after cerebral ischemia. We employed contrast enhancement MRI with Gd-DTPA
      to detect HT in a rat model of embolic stroke treated with rtPA and a
      glycoprotein IIb/IIIa receptor antagonist, 7E3 F(ab')2, at 4 h after embolic
      stroke. Male Wistar rats were subjected to embolic stroke and treated with the
      combination of rtPA and 7E3 F(ab')2 (n=12) or with saline (n=10) at 4 h after
      onset of stroke. MRI studies were performed immediately and at 24 h after
      embolization using a 7-T system. Histological measurements were obtained at 48 h.
      With Gd-DTPA, T1WI images and permeability related MRI parameters (the blood-to
      brain transfer constant, Ki, and the distribution volume of mobile protons, Vp)
      of 15 out of 18 animals showed hyperintensity regions in gross or microscopic HT
      areas at 24 h, confirmed histologically at 48 h post stroke. Contrast enhancement
      MRI detected six of seven (86%) animals with gross HT and nine of eleven (82%)
      animals with microscopic HT at 24 h after ischemia. Two of eighteen animals with
      HT, had MRI indices of hemorrhage at 3 h post stroke. However, compared to HT
      data measured histologically at 48 h in embolic stroke rats, the enhanced areas
      by Gd-DTPA at 24 h were larger, and the patterns (time, intensity and region) did
      not directly correlate to the subtypes of HT, i.e., gross or microscopic
      hemorrhage. Contrast enhancement MRI using Gd-DTPA provides a method to detect
      gross and microscopic HT after stroke in rats.

PMID- 16950237
TI  - Mitochondrial uncoupling, with low concentration FCCP, induces ROS-dependent
      cardioprotection independent of KATP channel activation.
AB  - OBJECTIVE: Both K(ATP) channel opening drugs and ischaemic preconditioning have
      been suggested to protect the ischaemic heart by acting on K(ATP) channels in the
      inner mitochondrial membrane, uncoupling the proton gradient and partially
      dissipating the mitochondrial membrane potential. The aim of these studies was to
      use low concentrations of FCCP, a mitochondrial protonophore, to bypass the
      mitochondrial K(ATP) channel and partially uncouple the mitochondria and
      establish whether this activates protective pathways within the rat heart
      analogous to K(ATP) channel openers or preconditioning. METHODS: Isolated,
      Langendorff-perfused rat hearts were subjected to 25 min global zero-flow
      ischaemia and functional recovery assessed. Hearts were pretreated with FCCP (30
      300 nM) in the presence or absence of glibenclamide (1 microM), 5
      hydroxydecanoate (5-HD: 100 microM), N-acetyl cysteine (4 mM), or N-2
      mercaptopropionyl glycine (1 mM). The metabolic consequences of FCCP perfusion in
      isolated hearts were studied using (31)P NMR, and reactive oxygen species (ROS)
      production was measured using DCF fluorescence in isolated rat ventricular
      myocytes. RESULTS: FCCP exerted a dose-dependent cardioprotective effect, with
      100 nM FCCP being the optimal concentration. This effect could not be blocked by
      glibenclamide or 5-HD, but was completely attenuated by N-acetyl cysteine and N-2
      mercaptopropionyl glycine. Perfusion with FCCP (100 nM) did not deplete bulk ATP
      during the pretreatment period but significantly depleted phosphocreatine. In
      ventricular myocytes, FCCP caused an antioxidant-sensitive increase in ROS
      production but diazoxide was without effect. CONCLUSIONS: In the isolated rat
      heart, partial mitochondrial uncoupling with low-dose FCCP significantly improves
      post-ischaemic functional recovery via a ROS-dependent pathway. This
      cardioprotection is not mediated via the depletion of cellular ATP or
      mitochondrial K(ATP) channel activation.

PMID- 16950238
TI  - Circadian rhythm of serum concentration of small dense low-density lipoprotein
      cholesterol.
AB  - BACKGROUND: The atherogenicity of small dense low-density lipoprotein (sdLDL) has
      been reported and recently a new easy-handling method for measuring serum
      concentration of sdLDL cholesterol (sdLDLC) has been developed. Using this
      method, we observed the circadian rhythm of sdLDLC to determine the adequacy of
      fasting measurement of it and to seek the modulator of the atherogenic
      lipoprotein. METHODS: Study population was consisted of 20 healthy volunteers (10
      women and 10 men, mean age 28 y). They had 3 meals per day and blood samples were
      taken before and 2 h after every meal and next morning. Serum concentrations of
      sdLDLC and other valuables including triglyceride (TG) and remnant-like particles
      cholesterol (RLPC) were determined. RESULTS: Serum concentration of sdLDLC had a
      unique circadian rhythm that was highest before breakfast (fasting status),
      decreased after each meal, hit the bottom after dinner and then increased during
      at night. Fasting sdLDLC was highly correlated with TG levels. The sum of the 6
      TG values during a day (i.e., average TG level) had higher correlation
      coefficient with sdLDLC than fasting TG or fasting RLPC. CONCLUSIONS: From the
      observation of the unique circadian rhythm, measuring sdLDLC at fasting status is
      exactly reasonable because it never underestimate the risk of atherosclerotic
      diseases. Measuring sdLDLC can also be used as a marker for average TG levels
      regardless of the existence of postprandial hyperlipidemia.

PMID- 16950239
TI  - Affective evaluations of objects are influenced by observed gaze direction and
      emotional expression.
AB  - Gaze direction signals another person's focus of interest. Facial expressions
      convey information about their mental state. Appropriate responses to these
      signals should reflect their combined influence, yet current evidence suggests
      that gaze-cueing effects for objects near an observed face are not modulated by
      its emotional expression. Here, we extend the investigation of perceived gaze
      direction and emotional expression by considering their combined influence on
      affective judgments. While traditional response-time measures revealed equal gaze
      cueing effects for happy and disgust faces, affective evaluations critically
      depended on the combined product of gaze and emotion. Target objects looked at
      with a happy expression were liked more than objects looked at with a disgust
      expression. Objects not looked at were rated equally for both expressions. Our
      results demonstrate that facial expression does modulate the way that observers
      utilize gaze cues: Objects attended by others are evaluated according to the
      valence of their facial expression.

PMID- 16950240
TI  - Nuclear and chromatin reorganization in the MHC-Oct3/4 locus at developmental
      phases of embryonic stem cell differentiation.
AB  - Epigenetic gene control is involved in mechanisms of development. Little is known
      about the cooperation of nuclear and chromatin events in programmed
      differentiation from mouse embryonic stem cells (ESC). To address this, Oct3/4
      positive ESC and differentiated progenies, Sox1-positive neural precursor cells
      (NPC) and post-mitotic neurons (PMN), were isolated using a stage-selected
      culture system. We first investigated global nuclear organization at the each
      stage. Chromocenter preexists in ESC, disperses in NPC and becomes integrated
      into large heterochromatic foci in PMN, while the formation of PML bodies
      markedly decreases in neural differentiation. We next focused on the gene-dense
      MHC-Oct3/4 region. Oct3/4 gene is expressed preferentially adjacent to PML bodies
      in ESC and are repressed in the absence of chromocenter association in NPC and
      PMN. Histone deacetylation in NPC, demethylation of lysine 4 of histone H3
      (H3K4), tri-methylation of H3K27, and CpG methylation in PMN are targeted for the
      Oct3/4 promoter within the region. Interestingly, di-methyl H3K4 mark is present
      in Oct3/4 promoter in NPC as well as ESC. These findings provide insights into
      the molecular basis of global nuclear reorganization and euchromatic gene
      silencing in differentiation through the spatiotemporal order of epigenetic
      controls.

PMID- 16950241
TI  - Overlapping expression of FoxA and Zic confers responsiveness to FGF signaling to
      specify notochord in ascidian embryos.
AB  - Differences in cell responsiveness to an inductive signal contribute to the
      emergence of a variety of tissue types during animal development. In ascidian
      embryos, the Fibroblast Growth Factor (FGF) signal secreted from endoderm cells
      induces several different tissue types, such as notochord, mesenchyme and brain,
      at different positions in the embryo at the 32-cell stage. We show here in
      Halocynthia roretzi that FoxA and Zic are required for notochord formation in
      cells that receive the FGF signal. We also show that these transcription factors,
      only when both are supplied, are able to induce ectopic expression of the
      brachyury gene, a notochord-specific marker, in cells of all the three germ
      layers in an FGF-dependent manner. These results suggest that FoxA and Zic confer
      notochord-specific responsiveness to FGF signaling. Further analyses including
      knockdown and over-expression experiments showed that combinatorial inputs from
      maternally supplied and zigotically activated factors lead to overlapping
      expression of FoxA and Zic in the presumptive notochord cells, which eventually
      activate the expression of the brachyury gene in cooperation with FGF signaling.
      Our data illustrate how a complex gene network specifies the notochord at its
      specific position within the embryo.

PMID- 16950242
TI  - The echinoderm adhesome.
AB  - Although the development of sea urchin embryos has been studied extensively and
      clearly involves both cell adhesion and cell migration, rather little is known
      about the adhesion receptors and extracellular matrix molecules involved. The
      completion of the genome of Strongylocentrotus purpuratus allows a comprehensive
      survey of the complement of cell-cell and cell-matrix adhesion molecules in this
      organism. Furthermore, the phylogenetic position of echinoderms offers the
      opportunity to compare the complement of adhesion proteins between protostome and
      deuterostome invertebrates and between invertebrate and vertebrate deuterostomes.
      Many aspects of development and cell interactions differ among these different
      taxa and it is likely that analysis of the spectrum of adhesion receptors and
      extracellular matrix proteins can open up new insights into which molecules have
      evolved to suit particular developmental processes. In this paper, we report the
      results of an initial analysis along these lines. The echinoderm adhesome
      (complement of adhesion-related genes/proteins) is similar overall to that of
      other invertebrates although there are significant deuterostome-specific
      innovations and some interesting features previously thought to be chordate or
      vertebrate specific.

PMID- 16950243
TI  - Phytoestrogen derivatives differentially inhibit arterial neointimal
      proliferation in a mouse model.
AB  - Neointimal proliferation is a key element in atherosclerotic plaque formation and
      in arterial restenosis following angioplasty. Estrogen-like compounds, including
      naturally occurring plant phytoestrogens, are known to alter the extent of
      neointimal proliferation. This study investigates the anti-atherogenic/restenotic
      effect of several synthetic metabolites of isoflavone phytoestrogens
      (dihydrodaidzein, tetrahydrodaidzein and dehydroequol) (Novogen, Sydney,
      Australia). Acute neointimal proliferation was induced in the iliac artery of
      cholesterol-fed mice, by mechanically damaging the endothelium. Phytoestrogens
      were administered orally for 4 weeks and the damaged arteries harvested. Intimal
      area, as a percentage of the iliac artery wall area, was measured.
      Dihydrodaidzein significantly halved the intimal response (intima approximately
      25% of wall area; p < 0.01) compared with placebo diet-fed mice (intima
      approximately 50% of wall area), while tetrahydrodaidzein and dehydroequol showed
      no inhibitory effects. Immunohistochemistry demonstrated that alpha-actin
      positive vascular smooth muscle cells were the major cell type in the
      proliferating neointima. A single layer of endothelium covered the thickened
      intima by 4 weeks. Thus, a specific phytoestrogen isoflavone compound
      (dihydrodaidzein) can selectively inhibit neointimal proliferation, either by
      inhibition of vascular smooth muscle cell migration and proliferation, and/or by
      enhancing endothelial proliferation and function, and inhibition of endothelial
      apoptosis.

PMID- 16950244
TI  - Neutrophil elastase sorting involves plasma membrane trafficking requiring the C
      terminal propeptide.
AB  - The primary granules/secretory lysosomes of neutrophils store mature neutrophil
      elastase (NE) as a luminal protein after proteolytic removal of N-terminal and C
      terminal pro-peptides from a proform of NE. The N-terminal pro-peptide prevents
      premature activation that might be toxic to the cell, but the C-terminal pro
      peptide has no defined function. In this study, we investigated the role of the C
      terminal pro-peptide in trafficking of NE by expressing, in rat basophilic
      leukemia (RBL) cells, both wild-type NE and the mutant NE/Delta248-267, which
      lacks the C-terminal pro-peptide. Both transfected proteins were found to be
      targeted to secretory lysosomes. In addition, results from antibody ligation and
      cell-surface biotinylation indicated that proform of NE was targeted to the
      plasma membrane, and then subjected to endocytosis. The results were supported by
      the detection of targeting of the proform to the plasma membrane followed by
      internalization both in RBL cells and normal granulopoietic precursor cells.
      Targeting of NE to the plasma membrane required the C-terminal pro-peptide as
      NE/Delta248-267 expressed in RBL cells bypassed plasma membrane trafficking. Our
      results indicate targeting of a population of NE to the plasma membrane and
      internalization dependent on the C-terminal NE pro-peptide.

PMID- 16950245
TI  - Interaction between HP1alpha and replication proteins in mammalian cells.
AB  - HP1 is an essential heterochromatin-associated protein known to play an important
      role in the organization of heterochromatin as well as in the transcriptional
      regulation of heterochromatic and euchromatic genes both in repression and
      activation. Using the yeast two-hybrid system and immunoprecipitation, we report
      here that murine HP1alpha interacts with the preRC proteins ORC1, ORC2 and CDC6.
      Immunofluorescence staining and EGFP/DsRed fusion proteins revealed a
      colocalization of HP1alpha with ORC1, ORC2 and CDC6 in heterochromatin,
      supporting the notion that ORC and probably CDC6 play an important role in murine
      HP1alpha function. Besides that, we also observed a colocalization of HP1alpha
      with gamma-tubulin suggesting a centrosomal localization of HP1alpha in murine
      cells. To gain insight into HP1alpha function, we applied the RNAi technique.
      Depletion of HP1alpha leads to a slow down of cell proliferation, an aberrant
      cell cycle progression as well as to multinucleated cells with insufficiently
      organized microtubule. These results together indicate that HP1alpha exerts
      functions in mitosis and cytokinesis.

PMID- 16950246
TI  - Patterns of transorbital intracranial injury: a review and comparison of occult
      and non-occult cases.
AB  - The authors present an illustrative case of occult transorbital penetrating
      intracranial injury in a child, and review the literature concerning patterns of
      low-velocity, non-projectile injury during the era of modern CT and MRI study.
      Review of the mechanism of injury and analysis of surface entry site of
      penetration in 38 cases suggests recurring patterns of injury in occult and non
      occult cases. A classification system based on surface entry zone site is applied
      to these injuries. Knowledge of the classification system should increase
      clinical suspicion for this type of often occult, penetrating orbito-cranial
      injury and direct appropriate investigation to provide earlier detection and
      diagnosis of the transorbital, intracranial penetration.

PMID- 16950247
TI  - Photochemical damage of the retina.
AB  - Visual perception occurs when radiation with a wavelength between 400 and 760 nm
      reaches the retina. The retina has evolved to capture photons efficiently and
      initiate visual transduction. The retina, however, is vulnerable to damage by
      light, a vulnerability that has long been recognized. Photochemical damage has
      been widely studied, because it can cause retinal damage within the intensity
      range of natural light. Photochemical lesions are primarily located in the outer
      layers at the central region of the retina. Two classes of photochemical damage
      have been recognized: Class I damage, which is characterized by the rhodopsin
      action spectrum, is believed to be mediated by visual pigments, with the primary
      lesions located in the photoreceptors; whereas Class II damage is generally
      confined to the retinal pigment epithelium. The action spectrum peaks in the
      short wavelength region, providing the basis for the concept of blue light
      hazard. Several factors can modify the susceptibility of the retina to
      photochemical damage. Photochemical mechanisms, in particular mechanisms that
      arise from illumination with blue light, are responsible for solar retinitis and
      for iatrogenic retinal insult from ophthalmological instruments. Further, blue
      light may play a role in the pathogenesis of age-related macular degeneration.
      Laboratory studies have suggested that photochemical damage includes oxidative
      events. Retinal cells die by apoptosis in response to photic injury, and the
      process of cell death is operated by diverse damaging mechanisms. Modern
      molecular biology techniques help to study in-depth the basic mechanism of
      photochemical damage of the retina and to develop strategies of neuroprotection.

PMID- 16950248
TI  - Clinical corneal confocal microscopy.
AB  - Confocal microscopy allows non-invasive in vivo imaging of the ocular surface.
      Its unique physical properties enable microscopic examination of all layers of
      the cornea and have been used to investigate numerous corneal diseases:
      epithelial changes, numerous stromal degenerative or dystrophic diseases,
      endothelial pathologies, corneal deposits, infections, and traumatic lesions. It
      offers a new approach to study the physiological reactions of the cornea to
      different stimuli and the pathophysiologic events leading to corneal dysfunction
      in certain diseases. Confocal microscopy proves to be a powerful diagnostic tool
      and is especially of value in certain corneal diseases by allowing
      straightforward and non-invasive recognition of the pathologic conditions.

PMID- 16950249
TI  - alpha(1)-Adrenergic receptor antagonists and the iris: new mechanistic insights
      into floppy iris syndrome.
AB  - Understanding the role of adrenergic receptors in iris biology has gained
      widespread interest due to the recently described intraoperative floppy iris
      syndrome sometimes encountered during cataract surgery. alpha(1)AR-mediated iris
      dilator smooth muscle contraction occurs via alpha(1a)ARs whereas alpha(1b)ARs
      mediate iris arteriolar contraction. Because alpha(1)AR antagonists are first
      line therapy for benign prostatic hyperplasia and lower urinary tract symptoms,
      more elderly patients requiring cataract surgery now receive these drugs. After
      reviewing intraoperative floppy iris syndrome, strengths/weaknesses of supporting
      data, and reviewing iris biology, a case is made that rather than being drug
      specific (alpha(1)AR antagonists), intraoperative floppy iris syndrome may
      represent the "tip of the iceberg." Relaxed iris dilator muscle resistant to
      adrenergic agonists should be expected with clinical drugs shown to relax the
      iris dilator (e.g., antagonists at alpha(1)AR, endothelin-A, angiotensin
      receptors, nitric oxide donors such as nitrates), and/or diseases associated with
      endothelial dysregulation (e.g., congestive heart failure, diabetes,
      hypertension). Rather than a rare, unexpected, unpredictable syndrome due to one
      drug, a careful medical history should elucidate intraoperative floppy iris
      syndrome predisposition. Just as anticoagulants are discontinued prior to
      elective surgery, conservative management of elderly patients suggests
      discontinuation of drugs that relax iris dilator muscle, in consultation with the
      patient's primary physician, should be considered prior to cataract surgery.

PMID- 16950250
TI  - Conjunctival mucoepidermoid carcinoma in a patient with ocular cicatricial
      pemphigoid and a review of the literature.
AB  - Invasive mucoepidermoid carcinoma of the conjunctiva of the left lower eyelid was
      diagnosed in an orbital exenteration specimen of a 57-year-old woman, after a
      biopsy of the same lesion was originally diagnosed as invasive squamous cell
      carcinoma. The woman was undergoing mitomycin C injections for ocular cicatricial
      pemphigoid, diagnosed in the same eye 2 years prior to identification of the
      neoplasm. The tumor invaded the cornea, sclera, lacrimal gland, regional small
      nerves, and lymphatics, but did not show intraocular involvement. The original
      biopsy specimen was reassessed with stains for mucin and found to be
      mucoepidermoid carcinoma of the conjunctiva. We reviewed 21 cases of
      mucoepidermoid carcinoma of the conjunctiva described to date in the English
      literature. We believe this number underestimates the true incidence of this
      condition, as it is frequently misdiagnosed both clinically and
      histopathologically. Evaluating suspected aggressive squamous cell carcinoma with
      special stains for mucin generally helps to identify mucoepidermoid carcinoma of
      the conjunctiva. More extensive surgical excision than that used for squamous
      cell carcinoma should be implemented in the management of mucoepidermoid
      carcinoma of the conjunctiva to prevent recurrence.

PMID- 16950251
TI  - Too young to...
AB  - A 22-year-old woman presents with headache and an acquired cranial nerve VI
      palsy. The differential diagnosis and work-up were negative. The causes of
      cranial nerve VI palsy in young patients are discussed. Follow-up for patients in
      this age group is also discussed.

PMID- 16950252
TI  - Analysis of the National Health and Nutrition Examination Survey. Comment on
      "Prevalence of visual impairment in the United States", by S Vitale, MF Cotch,
      and RD Sperduto. JAMA 295:2158-63, 2006.
AB  - CONTEXT: The prevalence of visual impairment in the U.S. public has not been
      surveyed nationally in several decades. OBJECTIVE: To estimate the number of U.S.
      individuals aged 12 years or older who have impaired distance vision due to
      uncorrected refractive error. DESIGN, SETTING, AND PARTICIPANTS: The National
      Health and Nutrition Examination Survey (NHANES), using a multistage probability
      sampling design, included a vision evaluation in a mobile examination center.
      Visual acuity data were obtained from 13,265 of 14,203 participants (93.4%) who
      visited the mobile examination center in 1999-2002. Visual impairment was defined
      as presenting distance visual acuity of 20/50 or worse in the better-seeing eye.
      Visual impairment due to uncorrected refractive error was defined as (presenting)
      visual impairment that improved, aided by automated refraction results, to 20/40
      or better in the better-seeing eye. MAIN OUTCOME MEASURES: Presenting distance
      visual acuity (measured with usual corrective lenses, if any) and distance visual
      acuity after automated refraction. RESULTS: Overall, 1,190 study participants had
      visual impairment (weighted prevalence, 6.4%; 95% confidence interval [CI], 6.0
      6.8%), and of these, 83.3% could achieve good visual acuity with correction (95%
      CI, 80.9-85.8%). Extrapolating these findings to the general U.S. population,
      approximately 14 million individuals aged 12 years or older have visual
      impairment (defined as distance visual acuity of 20/50 or worse), and of these,
      more than 11 million individuals could have their vision improved to 20/40 or
      better with refractive correction. CONCLUSIONS: Visual impairment due to
      uncorrected refractive error is a common condition in the United States.
      Providing appropriate refractive correction to those individuals whose vision can
      be improved is an important public health endeavor with implications for safety
      and quality of life.

PMID- 16950253
TI  - The manifold actions of statins. Comment on "Effects of systemic administration
      of simvastatin on retinal circulation, by T. Nagaoka, A. Takahashi, E. Sato, et
      al. Arch Ophthalmol 124:665-70, 2006.
AB  - OBJECTIVE: To investigate the effect of systemic administration of simvastatin on
      the retinal circulation. METHODS: The effects of systemic administration of
      simvastatin on the retinal circulation after 90 minutes and after 7 days were
      studied in a placebo-controlled, double-masked, clinical trial among 12 healthy
      men. We used laser Doppler velocimetry to measure vessel diameter and blood
      velocity and calculated the blood flow in retinal arteries and veins. We also
      measured the intraocular pressure and the plasma nitrite/nitrate levels, the
      stable end products of nitric oxide metabolism. RESULTS: There were no
      significant changes in any retinal circulatory parameters at 90 minutes after
      administration of simvastatin. Daily administration of simvastatin for 7 days
      significantly increased blood velocity and blood flow in retinal arteries and
      veins but did not significantly change vessel diameter. The intraocular pressure
      significantly decreased at 90 minutes and at 7 days after administration of
      simvastatin. Simvastatin also significantly increased the plasma nitrite/nitrate
      levels. CONCLUSION: Simvastatin induced an increase in blood velocity and blood
      flow in retinal arteries and veins, increased the plasma nitrite/nitrate levels,
      and decreased the intraocular pressure, probably through the increase in nitric
      oxide.

PMID- 16950254
TI  - Ocular pharmacokinetics of moxifloxacin after topical treatment of animals and
      humans.

PMID- 16950256
TI  - Age-related macular degeneration is a cause of centrotyphlosis but not of
      blindness.

PMID- 16950258
TI  - Trans-scleral delivery of polyamine analogs for ocular neovascularization.
AB  - Periocular injections of the polyamine analog CGC-11144 three times a week causes
      regression of choroidal neovascularization. This regimen was selected to maximize
      chances of success for proof of concept, but is not ideal for clinical
      application. In this study we explored other regimens for periocular delivery of
      CGC-11144, and 2 other polyamine analogs, CGC-11047 and CGC-11093. A single
      periocular injection of 200 microg of CGC-11144, 2 mg of CGC-11047, or 1.5 mg of
      CGC-11093 caused significant suppression and regression of laser-induced
      choroidal neovascularization. An injection of 2 mg of CGC-11047 or 1.5 mg of CGC
      11093 one or two weeks before, but not 3 weeks before, rupture of Bruch's
      membrane also caused significant suppression. Periocular injection of polyamine
      analogs also caused strong inhibition of retinal or subretinal neovascularization
      in mice with oxygen-induced ischemic retinopathy or Rhodopsin promoter/VEGF
      transgenic mice, respectively. These data suggest that periocular injection of
      one of 3 different polyamine analogs inhibits retinal or choroidal
      neovascularization and a single injection provides inhibitory activity for at
      least 2 to 3 weeks, which could provide the basis for a feasible treatment
      regimen for clinical trials.

PMID- 16950259
TI  - Volumetric magnetic resonance imaging of dorsal root ganglia for the objective
      quantitative assessment of neuron death after peripheral nerve injury.
AB  - Prevention of neuron death after peripheral nerve injury is vital to regaining
      adequate cutaneous innervation density and quality of sensation, and while
      experimentally proven neuroprotective therapies exist, there lacks suitable
      clinical outcome measures for translational research. Axotomized dorsal root
      ganglia (DRG) histologically exhibit volume reduction in proportion to the amount
      of neuronal death within them. Hence, this study evaluated the validity of using
      magnetic resonance imaging (MRI) to quantify DRG volume as a proxy measure of
      cell death. A high-resolution 3D MRI sequence was developed for volumetric
      quantification of the L4 DRG in the rat sciatic nerve model. An unoperated
      "control" group (n=4), and a "nerve transection" group (n=6), 4 weeks after
      axotomy, were scanned. Accuracy and validity of the technique were evaluated by
      comparison with morphological quantification of DRG volume and stereological
      counts of surviving neurons (optical fractionator). The technique was precise
      (coefficient of variation=4.3%), highly repeatable (9% variability), and
      sensitive (mean 15.0% volume reduction in axotomized ganglia detected with
      statistical significance: p<0.01). MRI showed strong and highly significant
      correlation with morphological measures of DRG volume loss (r=0.90, p<0.001),
      which in turn correlated well with neuron loss (r=0.75, p<0.05). MRI similarly
      exhibited direct correlation with neuron loss (r=0.67, p<0.05) with consistent
      agreement. MRI volumetric quantification of DRG is therefore a valid in vivo
      measure of neuron loss. As a non-invasive, objective measure of neuronal death
      after nerve trauma this technique has potential as a diagnostic modality and a
      quantitative tool for clinical studies of neuroprotective agents.

PMID- 16950260
TI  - Respiratory behaviour of a Zymomonas mobilis adhB::kan(r) mutant supports the
      hypothesis of two alcohol dehydrogenase isoenzymes catalysing opposite reactions.
AB  - Perturbation of the aerobic steady-state in a chemostat culture of the ethanol
      producing bacterium Zymomonas mobilis with a small pulse of ethanol causes a
      burst of ethanol oxidation, although the reactant ratio of the alcohol
      dehydrogenase (ADH) reaction ([NADH][acetaldehyde][H(+)])/([ethanol][NAD(+)])
      remains above the K(eq) value. Simultaneous catalysis of ethanol synthesis and
      oxidation by the two ADH isoenzymes, residing in different redox
      microenvironments, has been proposed previously. In the present study, this
      hypothesis is verified by construction of an ADH-deficient strain and by
      demonstration that it lacks the oxidative burst in response to perturbation of
      its aerobic steady-state with ethanol.

PMID- 16950261
TI  - Antibodies with amylase activity from the sera of autoimmune-prone MRL/MpJ-lpr
      mice.
AB  - Animals spontaneously developing lupus-like autoimmune pathology (SLE) are very
      promising models to study the mechanisms of natural abzymes (Abzs) generation and
      their role in etiology and pathogenesis of autoimmune diseases, but Abzs from the
      sera of animals remain virtually unstudied. In this work, electrophoretically
      homogeneous IgGs were isolated from the sera of MRL/MpJ-lpr mice. It was shown
      for the first time that amylase activity is an intrinsic property of antibodies
      (Abs) and their isolated heavy and light chains. Various markers of SLE pathology
      (proteinuria, enhanced concentration of anti-DNA Abs) increased with spontaneous
      development of SLE and especially after animal immunization, correlating with the
      increase in Abz relative amylase activity. The highest amylase activity was found
      in the sera Abs of healthy mice after delivery and at the beginning of lactation;
      this was not correlated with markers of mouse SLE but supports the idea that
      pregnancy could "activate" or "trigger" autoimmune-like manifestations and Abzs
      production in healthy mammals. The possible differences in mechanisms of Abzs
      production in lactating mice and animals developing SLE are discussed.

PMID- 16950262
TI  - In vitro evaluation of the direct effect of estradiol on human osteoblasts (HOB)
      and human mesenchymal stem cells (h-MSCs).
AB  - Estrogen may increase the proliferation of osteoblasts depending upon their
      differentiation stage. Our objective was to test the hypothesis that estradiol
      could stimulate the proliferation of primary human osteoblast (HOB) cells or
      human mesenchymal stem cells (h-MSCs). To test this hypothesis, we investigated
      two synthetic estradiol preparations: (a) a commercially available one (in
      clinical use) whose effect was evaluated using MTT assay, trypan blue cell counts
      and total protein assays; (b) a novel synthetic preparation (not in clinical use)
      using Alamar Blue assays and scanning electron microscopy (SEM). Commercial
      estradiol increased HOB proliferation in a concentration-dependant manner between
      1 nM and 8 nM reaching significance at a concentration of 8 nM (p<0.001). Small
      doses of 1 nM and 2 nM increased h-MSC proliferation (p<0.001) but higher doses
      had no effect. All novel synthetic estradiol preparations decreased HOB
      proliferation (p<0.001) whereas no direct effect was observed on h-MSCs.
      Commercial estradiol appears to induce proliferation of HOBs, although its
      effects on h-MSCs appears to be highly dose-dependent and requires further
      investigation.

PMID- 16950263
TI  - A philosophy of care of open injuries based on the Ganga hospital score.
AB  - In the management of Type IIIb injuries, Gustilo's classification has the
      disadvantages of a poor intra and inter-observer agreement rate, low specificity
      and sensitivity to salvage and inability to predict functional outcomes. We
      propose here a validated score which assesses the severity of injury to the
      covering structures, skeletal structures and functional tissues of the injured
      limb separately along with providing weightage to the presence of co-morbid
      factors. A high sensitivity and specificity for amputation was documented when a
      score of 14 was used as the threshold score. In salvaged limbs, the score was
      found to offer guidelines in protocols for reconstruction. According to the total
      score, injuries were treated by 'Fix and close' protocol; 'Fix, Bone Graft and
      Close' protocol, 'Fix and Flap' protocol or 'Stabilise, Watch, Assess and
      Reconstruct' protocol. The score was thus found to be useful clinically not only
      to assess salvage but also to provide guidelines in reconstruction.

PMID- 16950264
TI  - Tissue engineering and bone regeneration.

PMID- 16950265
TI  - SL1 RNA gene recovery from Enterobius vermicularis ancient DNA in pre-Columbian
      human coprolites.
AB  - Enterobius vermicularis, pinworm, is one of the most common helminths worldwide,
      infecting nearly a billion people at all socio-economic levels. In prehistoric
      populations the paleoparasitological findings show a pinworm homogeneous
      distribution among hunter-gatherers in North America, intensified with the advent
      of agriculture. This same increase also occurred in the transition from nomad
      hunter-gatherers to sedentary farmers in South America, although E. vermicularis
      infection encompasses only the ancient Andean peoples, with no record among the
      pre-Colombian populations in the South American lowlands. However, the outline of
      pinworm paleoepidemiology has been supported by microscopic finding of eggs
      recovered from coprolites. Since molecular techniques are precise and sensitive
      in detecting pathogen ancient DNA (aDNA), and also could provide insights into
      the parasite evolutionary history, in this work we have performed a molecular
      paleoparasitological study of E. vermicularis. aDNA was recovered and pinworm 5S
      rRNA spacer sequences were determined from pre-Columbian coprolites (4110 BC-AD
      900) from four different North and South American archaeological sites. The
      sequence analysis confirmed E. vermicularis identity and revealed a similarity
      among ancient and modern sequences. Moreover, polymorphisms were identified at
      the relative positions 160, 173 and 180, in independent coprolite samples from
      Tulan, San Pedro de Atacama, Chile (1080-950 BC). We also verified the presence
      of peculiarities (Splicing leader (SL1) RNA sequence, spliced donor site, the Sm
      antigen biding site, and RNA secondary structure) which characterise the SL1 RNA
      gene. The analysis shows that the SL1 RNA gene of contemporary pinworms was
      present in pre-Columbian E. vermicularis by 6110 years ago. We were successful in
      detecting E. vermicularis aDNA even in coprolites without direct microscopic
      evidence of the eggs, improving the diagnosis of helminth infections in the past
      and further pinworm paleoepidemiological studies.

PMID- 16950266
TI  - Global patterns reveal strong population structure in Haemonchus contortus, a
      nematode parasite of domesticated ruminants.
AB  - We have examined the global population genetic structure of Haemonchus contortus.
      The genetic variability was studied using both amplified fragment length
      polymorphism (AFLP) and nad4 sequences of the mitochondrial genome. To examine
      the performance and information content of the two different marker systems,
      comparative assessment of population genetic diversity was undertaken in 19
      isolates of H. contortus, a parasitic nematode of small ruminants. A total of 150
      individual adult worms representing 14 countries from all inhabited continents
      were analysed. Altogether 1,429 informative AFLP markers were generated using
      four different primer combinations. Also, the genetic variation was high, which
      agrees with results from previous AFLP studies of nematode parasites of
      livestock. The genetic structure was high, indicating limited gene flow between
      the different isolates and populations from each continent mostly formed
      monophyletic groups in the phylogenetic analysis. However, for isolates
      representing Australia, Greece and one laboratory strain that originated from
      South Africa (WRS), there was no clear genetic relationship between the isolates
      and the distance between their geographical origins. Basically the same pattern
      was observed for the mitochondrial marker, although the phylogenetic analysis was
      less resolved than for AFLP. In contrast with previous findings on the population
      genetic structure of H. contortus, the calculation of population structure gave
      high values (Nst=0.59). The strong structure was present also for the four
      Swedish isolates (Nst=0.16) representing a small geographical area.

PMID- 16950268
TI  - The natural history of asthma.
AB  - Asthma begins most often in infants as wheezing with respiratory infections. If
      these episodes are mild and infrequent, asthma does not usually persist into the
      school years. However, if they are more frequent and severe, the asthma is likely
      to persist. After infancy, incidence falls and continues at about 100/100,000 for
      the rest of the lifespan. Allergic asthma develops most often in the second
      decade of life and frequently persists into adult years, but young patients with
      allergic asthma often enjoy a transient or even a permanent remission. More
      severe disease and continued allergen exposure cause persistence. Some patients
      with occupational asthma continue to have asthma long after exposure ceases.
      Asthma beginning after the fourth decade is usually intrinsic and may include the
      aspirin triad. Its severity tends to increase with time. Many middle-aged and
      elderly adults have a persistent decline in lung function that is retarded but
      not completely prevented by aerosol glucocorticoids. This loss of lung function
      is often the result of coexisting lung diseases, particularly bronchiectasis and
      COPD. Patients with asthma have the same overall rate and age of death as the
      general population, but are more likely to die of lung diseases, including
      cancer.

PMID- 16950269
TI  - Mechanisms of airway hyperresponsiveness.
AB  - Airway hyperresponsiveness (AHR) to direct (histamine and methacholine) and
      indirect (exercise, cold air, hyperventilation, AMP) challenges is a universal
      and defining feature of asthma. One component of AHR is transient or inducible
      and occurs after allergen exposure, for example, and improves occasionally
      rapidly after inhaled corticosteroids or environmental control. This transient
      airway hyperresponsiveness is more marked to the indirect stimuli. There are
      convincing data linking this component of AHR to airway inflammation; however,
      the precise mechanisms linking airway inflammation and hyperresponsiveness of the
      airway smooth muscle are not clear. The other component of AHR is more persistent
      and is relatively refractory to environmental control and inhaled
      corticosteroids. This is likely secondary to structural airway changes, which are
      collectively referred to as airway remodeling, and which are a result of the
      chronic (rather than the acute) effects of airway inflammation. This persistent
      AHR is best reflected by airway hyperresponsiveness to direct stimuli such as
      methacholine. The mechanisms are also uncertain, but reduced airway caliber,
      increased airway wall thickness, increased airway smooth muscle mass, and perhaps
      contractility likely all play a role.

PMID- 16950270
TI  - Among young children who wheeze, which children will have persistent asthma?

PMID- 16950271
TI  - Biomarker-driven care in asthma: are we there?
AB  - Clinical asthma management is limited by the lack of straightforward and
      clinically applicable techniques to assess control and appropriately adjust
      therapy. The availability of biomarkers associated with airway caliber,
      responsiveness, or inflammation has prompted interest in the application of these
      measures as surrogate asthma end points in clinical trials. Use of a biomarker as
      a surrogate outcome in practice is most appropriate in settings in which the
      effects of therapy on clinical disease, as experienced by patients, are fully
      captured by that biomarker. Recent studies suggest that although asthma therapies
      can alter various biomarkers, the relationship between these biomarker changes
      and important clinical outcomes is inconsistent. Because symptom-driven titration
      of therapy is feasible and effective, additional data demonstrating clinically
      important benefits of biomarker-driven care in asthma are needed to justify the
      logistic and economic burdens associated with clinical dissemination of these
      techniques.

PMID- 16950272
TI  - Does unconventional medicine work through conventional modes of action?
AB  - It is often maintained that although conventional medicine works by means of
      pharmacotherapy with predominantly proved effects, unconventional therapies are
      more or less spiritual therapeutic approaches without a scientific basis. We
      hypothesize that both conventional and unconventional medicine might be effective
      because of similar modes of action. Certainly, this does not imply that every
      unconventional method has any effect. Conventional and effective unconventional
      medicine might both work by means of pharmacology (eg, substances in medical
      herbs), including pharmacologic interactions between the 2 treatment options (eg,
      herbs and drugs with coagulation effects). Both conventional and unconventional
      treatments involve a considerable risk of side effects, which are sometimes even
      severe. In general, the pattern of side effects of alternative treatments is
      similar to that observed with the use of conventional medicine. The placebo
      effect and suggestive aspects are also apparent in both treatments. Furthermore,
      mind-body medicine (eg, use of relaxation techniques) might be explained by
      pathophysiologic mechanisms. Overall, many aspects seem to contribute to the
      mosaic of joint modes of action involved in both conventional and unconventional
      medicine. This might demystify the aura of some of the complementary and
      alternative approaches and might help to bring both conventional and
      unconventional approaches together on a scientific basis.

PMID- 16950273
TI  - Persistence, adherence, and effectiveness of combination therapy among adult
      patients with asthma.
AB  - BACKGROUND: Limited evidence exists on adherence and effectiveness of combination
      therapy (inhaled corticosteroids and long-acting beta(2)-agonists in the same
      inhaler) in asthma. OBJECTIVE: To compare persistence, adherence, and
      effectiveness between patients with asthma 16 to 44 years old starting
      combination or concurrent therapies (inhaled corticosteroids and long-acting
      beta(2)-agonists in 2 different inhalers). METHODS: This retrospective 1-to-1
      matched cohort included newly treated asthmatics with either a combination or
      concurrent therapy selected from the Regie de l'assurance maladie du Quebec
      database between 1999 and 2002. Persistence was determined by Kaplan-Meier and
      Cox regression analyses. Adherence was estimated by the number of prescriptions
      filled during the first year and compared between the 2 drug regimens using a
      linear regression model. Treatment effectiveness to reduce the rate of moderate
      to severe asthma exacerbations was estimated with Poisson regression models.
      RESULTS: Persistence fell to 10% and 5% after 12 months for combination and
      concurrent users, respectively. Combination users were found to be 17% less
      likely to stop their treatment (adjusted hazard ratio, 0.83; 95% CI, 0.78, 0.88)
      and filled on average 0.9 more prescription per year than concurrent users (P =
      .0001). Combination users were also found to be 17% less likely to have a
      moderate to severe asthma exacerbation (adjusted rate ratio, 0.83; 95% CI, 0.75,
      0.91). CONCLUSION: The observed differences in treatment persistence and
      adherence were found to be associated with a reduction in the rate of moderate to
      severe asthma exacerbations among combination users. CLINICAL IMPLICATIONS:
      Combination therapy might be preferred to concurrent therapy for patients with
      asthma with low adherence to controller therapies.

PMID- 16950274
TI  - Asthma 2005-2006: bench to bedside.
AB  - Asthma is a prevalent and complex syndrome with several phenotypic variants. The
      central features are bronchial inflammation and airway hyperresponsiveness. Many
      aspects of asthma, such as control of airway hyperresponsiveness, causative
      factors, and variable responses to treatment, remain poorly understood. This
      review highlights some of the latest insights into the pathogenesis of asthma
      that might ultimately bear on the development or choice of treatment modalities.

PMID- 16950275
TI  - Rhinoviruses in the pathogenesis of asthma: the bronchial epithelium as a major
      disease target.

PMID- 16950276
TI  - Human rhinovirus in bronchial epithelium of infants with recurrent respiratory
      symptoms.
AB  - BACKGROUND: Human rhinoviruses (HRVs) are a common cause of upper respiratory
      tract infections. There is growing evidence that HRVs are also important in lower
      respiratory tract infections and often induce asthma exacerbations. OBJECTIVE: We
      evaluated the presence of HRV in the lower respiratory tract by obtaining
      bronchial biopsies from infants with recurrent asthmalike respiratory symptoms.
      METHODS: A total of 201 steroid-naive infants age 3 to 26 months with recurrent
      respiratory symptoms for at least 4 weeks within the preceding 2 months were
      studied for lung function using body plethysmography. Bronchoscopy was performed
      in 68 children, and bronchial biopsies were available from 59 infants for HRV
      detection with in situ hybridization. RESULTS: Human rhinovirus was detected in
      21 of 47 (45%) specimens. Abnormal lung function (decreased airways conductance)
      was found in 18 of 21 (86%) HRV(+) infants and in 15 of 26 (58%) HRV(-) infants
      (P = .037). Occurrence of a respiratory infection in the 6 weeks preceding
      bronchoscopy correlated with HRV positivity (P = .036). CONCLUSION: Human
      rhinovirus is frequently found in the lower airways in infants with recurrent
      respiratory symptoms, and the majority of these HRV(+) infants also showed
      increased airway resistance. CLINICAL IMPLICATIONS: Human rhinovirus is a common
      pathogen causing upper and lower respiratory symptoms. Follow-up of these infants
      will reveal whether the presence of HRV in the bronchial biopsy and abnormal lung
      function with recurrent respiratory symptoms predicts subsequent asthma.

PMID- 16950277
TI  - Pulmonary distribution, regulation, and functional role of Trk receptors in a
      murine model of asthma.
AB  - BACKGROUND: Neurotrophins have been implicated in the pathogenesis of asthma
      because of their ability to promote hyperreactivity of sensory neurons and to
      induce airway inflammation. Hyperreactivity of sensory nerves is one key
      mechanism of airway hyperreactivity that is defined as an abnormal reactivity of
      the airways to unspecific stimuli, such as cold air and cigarette smoke.
      Neurotrophins use a dual-receptor system consisting of Trk receptor tyrosine
      kinases and the structurally unrelated p75 neurotrophin receptor. OBJECTIVE: The
      aim of this study was to characterize the distribution, allergen-dependent
      regulation, and functional relevance of the Trk receptors in allergic asthma.
      METHODS: BALB/c mice were sensitized to ovalbumin. After provocation with
      ovalbumin or vehicle aerosol, respectively, Trk receptor expression was analyzed
      in lung tissue by means of fluorescence microscopy and quantitative RT-PCR. To
      assess the functional relevance of Trk receptors in asthma, we tested the effects
      of the intranasally administered pan-Trk receptor decoy REN1826. Allergic airway
      inflammation was quantified and lung function was measured by using head-out body
      plethysmography. RESULTS: Trk receptors were expressed in neurons, airway smooth
      muscle cells, and cells of the inflammatory infiltrate surrounding the bronchi
      and upregulated after allergen challenge. Local application of REN1826 reduced IL
      4 and IL-5 cytokine levels but had no effect on IL-13 levels or the cellular
      composition of bronchoalveolar lavage fluid cells. Furthermore, REN1826 decreased
      broncho-obstruction in response to sensory stimuli, indicating a diminished
      hyperreactivity of sensory nerves, but did not influence airway smooth muscle
      hyperreactivity in response to methacholine. CONCLUSION: These results emphasize
      the important role of Trk receptor signaling in the development of asthma.
      CLINICAL IMPLICATIONS: Our data indicate that blocking of Trk receptor signaling
      might reduce asthma symptoms.

PMID- 16950278
TI  - IL-25 enhances allergic airway inflammation by amplifying a TH2 cell-dependent
      pathway in mice.
AB  - BACKGROUND: A novel IL-17 family cytokine, IL-25, has been reported to induce IL
      4, IL-5, and IL-13 production from undefined non-T/non-B cells and then induce
      T(H)2-type immune responses. However, the roles of IL-25 in inducing allergic
      airway inflammation remain unknown. OBJECTIVE: We sought to determine whether IL
      25 is involved in causing allergic airway inflammation. METHODS: We examined the
      expression of IL-25 mRNA in the lungs of sensitized mice on antigen inhalation.
      We also examined the effect of IL-25 neutralization by soluble IL-25 receptor on
      antigen-induced airway inflammation. We then generated IL-25 transgenic mice that
      express IL-25 specifically in the lung under the control of the Clara cells-10-kd
      protein promoter and investigated the effect of enforced IL-25 expression on
      antigen-induced airway inflammation. RESULTS: IL-25 mRNA was expressed in the
      lungs of sensitized mice on antigen inhalation, and the neutralization of IL-25
      by soluble IL-25 receptor decreased antigen-induced eosinophil and CD4(+) T-cell
      recruitment into the airways. The enforced expression of IL-25 in the lung itself
      failed to induce allergic airway inflammation, whereas the expression of IL-25
      significantly enhanced antigen-induced T(H)2 cytokine production, eosinophil and
      CD4(+) T cell recruitment, and goblet cell hyperplasia in the airways. Moreover,
      IL-25-induced enhancement of allergic airway inflammation was inhibited by the
      depletion of CD4(+) T cells or by the absence of signal transducer and activator
      of transcription 6. CONCLUSION: IL-25 enhances antigen-induced allergic airway
      inflammation by amplifying a T(H)2 cell-dependent pathway. CLINICAL IMPLICATIONS:
      IL-25 might be involved in the enhancement, prolongation, or both of T(H)2 cell
      mediated allergic diseases, such as asthma.

PMID- 16950279
TI  - Effects of established allergen sensitization on immune and airway responses
      after secondary allergen sensitization.
AB  - BACKGROUND: Spreading of sensitization with clinical manifestation of allergy is
      often observed in atopic individuals. OBJECTIVE: To investigate the effects of an
      established primary allergen sensitization on immune responses and airway
      inflammation/reactivity on secondary allergen sensitization and airway challenges
      in a murine model. METHODS: Balb/c mice were primarily sensitized
      intraperitoneally with ovalbumin or PBS, followed by systemic sensitization and
      airway challenges with latex extract as a secondary, unrelated allergen. Purely
      sham-sensitized animals were included as controls. In a second set of
      experiments, the primary and secondary allergens were switched. RESULTS:
      Sensitization with ovalbumin before sensitization with latex resulted in
      increased production of total and latex-specific (Hev b 3-specific) IgE and
      IgG(1), and enhanced secretion of T(H)2-cytokines by spleen mononuclear cells
      cultured with mitogen compared with single latex-sensitized mice. Furthermore,
      airway challenges of double-sensitized mice (ovalbumin + latex) with latex caused
      a significant increase in airway reactivity compared with purely latex-sensitized
      and challenged animals. These effects were dependent on dosing and timing of the
      primary sensitization in relation to the secondary sensitization and independent
      of the primary allergen used. CONCLUSION: Primary sensitization boosted systemic
      T(H)2 immune responses and enhanced the development of airway reactivity after
      sensitization and airway challenges with a secondary, unrelated allergen. This
      effect of consecutive priming was dependent on the strength of the primary
      sensitization but independent of the allergen used. The results explain the
      increased susceptibility toward sensitization spreading in atopic individuals.
      CLINICAL IMPLICATIONS: Because sensitization spreading is facilitated by primary
      sensitization, early prevention measurements or immunotherapy should be
      considered at this stage of monosensitization.

PMID- 16950280
TI  - Correlation between peripheral blood T-cell profiles and airway inflammation in
      atopic asthma.
AB  - BACKGROUND: Recent studies suggest that T(H)1/T(H)2 and T(C)1/T(C)2 cell
      imbalances are implicated in asthma pathogenesis. However, the relationship of T
      cell profiles to airway inflammation has not been understood. OBJECTIVE: The
      purpose of this study was to clarify the correlation between peripheral blood T
      cell profiles and airway inflammatory parameters. METHODS: Subjects included 21
      patients with atopic asthma and 20 healthy control subjects. After stimulation
      with phorbol 12-myristate 13-acetate and ionomycin, flow cytometry was used to
      analyze intracellular cytokine staining for IFN-gamma and IL-4 in peripheral
      blood CD4(+) and CD8(+) T cells. Airway inflammation was assessed by using
      exhaled nitric oxide analysis and induced sputum eosinophil counts. RESULTS:
      There were a significantly increased proportion of IL-4-producing CD4(+) T cells
      (median, 2.7% [interquartile range, 2.4% to 3.3%] vs 1.8% [interquartile range,
      1.3% to 2.7%]) and a lower ratio of IFN-gamma-producing/IL-4-producing CD4(+) T
      cells (7.3% [interquartile range, 5.8% to 9.5%] vs 10.0% [interquartile range,
      8.8% to 13.2%]) in asthmatic patients compared with in healthy subjects (P < .01)
      but no increase or decrease in the proportion of IFN-gamma-producing CD4(+) T
      cells. No significant difference was found in the proportion of IFN-gamma- or IL
      4-producing CD8(+) T cells between the 2 groups. The proportion of IL-4-producing
      CD4(+) T cells was significantly correlated with exhaled nitric oxide (r = 0.48,
      P < .05) and induced sputum eosinophil counts (r = 0.50, P < .05). CONCLUSION:
      These findings indicate a correlation between peripheral blood T(H)2 cytokine
      production and markers of airway inflammation. CLINICAL IMPLICATIONS: There is an
      association between immune function and clinical indicators in asthma.

PMID- 16950281
TI  - Associations of a novel IL4RA polymorphism, Ala57Thr, in Greenlander Inuit.
AB  - BACKGROUND: A novel IL4RA polymorphism, Ala57Thr, was identified in Greenlander
      Inuit. OBJECTIVE: We sought to determine whether the novel Thr57 allele is
      population specific and to assess the associations of Ala57Thr and Ile50Val with
      atopy in 2 Inuit populations. METHODS: Ala57Thr and Ile50Val were genotyped in
      651 Inuit living in Denmark, 1295 Inuit living in Greenland, and 1329 individuals
      from 7 populations from widely differing global locations. In Inuit the
      polymorphisms were evaluated for associations with atopy, rhinitis, asthma, and
      pulmonary function. RESULTS: Thr57 was in linkage disequilibrium with Ile50 (D' =
      1, r(2) = 0.13) and was common (33%) in the Inuit but rare (<0.6%) in all other
      populations. In Inuit living in Denmark, the Thr57 allele (in a dose-dependent
      manner) and the Ile50/Thr57 haplotype were associated with lower risk of atopy
      (P(linear) = .003 and P = .034, respectively), with similar trends observed for
      atopic rhinitis and atopic asthma. In Inuit living in Greenland, Thr57 was not
      associated with atopy or atopic diseases, but Ile50 was weakly associated with
      lower risk of atopy. CONCLUSION: The novel IL4RA Ala57Thr was common in and
      population specific to Greenlander Inuit, with Thr57 associated with a lower risk
      of atopy in those living in Denmark. Hence a full investigation of genotype
      phenotype relationships in a given population can only be achieved if each gene
      is screened for novel polymorphisms in that population. CLINICAL IMPLICATIONS:
      Clinical risk attributable to variations in a gene in an ethnic group requires
      that all variations of the gene are known for that group.

PMID- 16950282
TI  - Urine leukotriene E4 levels are associated with decreased pulmonary function in
      children with persistent airway obstruction.
AB  - BACKGROUND: Use of leukotriene receptor antagonists improves disease control in
      children and adults with asthma. However, the relationship between cysteinyl
      leukotriene levels and indices of daily asthma control has not been studied
      directly. OBJECTIVES: We sought to assess the relationship between daily
      variability in urinary leukotriene E(4) (LTE(4)) levels and daily lung function
      in children primarily taking inhaled corticosteroids (ICSs) and long-acting beta
      agonists (LABAs). METHODS: Fifty children primarily with moderate-to-severe
      asthma were followed with measurements of urinary LTE(4), monitoring of FEV(1),
      and albuterol use. RESULTS: Increasing urinary LTE(4) levels were associated with
      significant (P = .006) decreases in percent predicted FEV(1) (ppFEV(1)) averaging
      4.7% per interquartile range increase in LTE(4) and accompanied by increased
      albuterol use (P = .03). Children with lower FEV(1)/forced vital capacity ratios
      demonstrated larger LTE(4)-related FEV(1) decreases (6.4%) compared to those with
      higher ratios (4.2%, P = .009). This association was blunted in children taking
      montelukast (1.4% ppFEV(1) decrease) compared with that in children not taking
      this medication (5.4% ppFEV(1) decrease, P = .05). Children with lower lung
      function ratios demonstrated greater blunting of the LTE(4) effect with
      montelukast (0.9% ppFEV(1) decrease) compared to those with higher ratios (3.6%
      ppFEV(1), P = .0002). CONCLUSIONS: Daily variability in LTE(4) levels is
      associated with clinically significant decreases in pulmonary function. In
      children who demonstrate a response associated with an increase in urinary LTE(4)
      levels, leukotriene receptor antagonists protect against daily FEV(1) decreases.
      This protection might be greatest in those with persistent airway obstruction
      despite use of ICS and LABA therapy. CLINICAL IMPLICATIONS: Therapies designed to
      block cysteinyl leukotriene production or function might benefit children
      receiving ICS and LABA therapy who continue to experience persistent disease.

PMID- 16950283
TI  - Toll-like receptor 2, 3, and 4 expression and function in human airway smooth
      muscle.
AB  - BACKGROUND: Host defense against microbial pathogens is elicited through the
      innate immune system by means of Toll-like receptors (TLRs). Airway smooth muscle
      cells (ASMCs) display proinflammatory and immunomodulatory functions. ASMCs might
      participate in airway inflammatory responses associated with innate immune
      activation. OBJECTIVES: We determined the effects of cytokines, TLR ligands, and
      corticosteroids on TLR expression and function in human ASMCs. METHODS: Real-time
      PCR and flow cytometry were used to assess TLR mRNA and protein expression,
      respectively. ASMCs were stimulated with TLR ligands, and chemokine release was
      measured by means of ELISA. RESULTS: ASMCs expressed TLR1 to TLR10 mRNA, and TLR2
      and TLR3 protein expression was demonstrated. TNF-alpha and double-stranded RNA
      (dsRNA; TLR3 ligand) were potent inducers of TLR2 and TLR3 mRNA expression, and
      both stimuli had additive or synergistic effects with IFN-gamma on TLR2 and TLR4,
      but not TLR3, mRNA expression. Peptidoglycan (TLR2 ligand) and LPS (TLR4 ligand)
      weakly enhanced TLR2 mRNA expression. Peptidoglycan, dsRNA, and LPS induced IL-8
      and eotaxin release, with dsRNA being most potent. dsRNA also modulated cytokine
      induced chemokine release in a differential manner. Dexamethasone inhibited
      cytokine- and ligand-induced TLR2, TLR3, and TLR4 expression and chemokine
      release. However, dexamethasone potentiated TLR2 expression induced by combined
      IFN-gamma and TNF-alpha stimulation. CONCLUSION: Expression of TLR2, TLR3, and
      TLR4 is regulated by cytokines and TLR ligands, and their activation mediates
      chemokine release in ASMCs. CLINICAL IMPLICATIONS: Proinflammatory responses
      mediated by activation of pathogen-recognition receptors in ASMCs might
      contribute to infectious exacerbations of airway inflammatory conditions, such as
      asthma and chronic obstructive pulmonary disease.

PMID- 16950284
TI  - A phosphodiesterase 4 inhibitor inhibits matrix protein deposition in airways in
      vitro.
AB  - BACKGROUND: Airway smooth muscle (ASM) cells may contribute to airway remodeling
      through the release of growth factors, cytokines, and extracellular matrix (ECM)
      proteins. The effect of current asthma therapies on this release is not known.
      OBJECTIVE: We examined the effect of corticosteroids, long-acting beta(2)
      agonists, and a phosphodiesterase 4 (PDE4) inhibitor on ASM-released connective
      tissue growth factor (CTGF), collagen I, fibronectin, versican, and IL-6.
      METHODS: Airway smooth muscle cells from individuals with and without asthma were
      stimulated with TGF-beta with or without the drugs and CTGF and ECM protein
      expression measured by real-time PCR, cell surface, or matrix-associated ELISA.
      IL-6 release was measured by ELISA. Bronchial rings from individuals without
      asthma were incubated with TGF-beta with or without the drugs. RESULTS: Neither
      corticosteroids nor long-acting beta(2)-agonists reduced TGF-beta-induced CTGF,
      collagen I, or fibronectin in either cell type, whereas corticosteroids alone
      induced the expression of CTGF, collagen I, and fibronectin. These drugs did not
      prevent the accumulation of TGF-beta-induced proteins in bronchial rings, whereas
      the PDE4 inhibitor roflumilast inhibited TGF-beta-induced CTGF, collagen I, and
      fibronectin. CONCLUSION: In our model, current asthma therapies are not able to
      inhibit matrix protein deposition from ASM cells. The results of this study
      suggest that the PDE4 inhibitor roflumilast may have a role in regulating the ECM
      and therefore aspects of airway remodeling in asthma. CLINICAL IMPLICATIONS:
      Although current asthma therapies are effective in reducing inflammation and
      symptoms, reversal or prevention of structural changes contributing to remodeling
      may require additional therapy, which could include PDE4 inhibitors.

PMID- 16950285
TI  - Association between farm exposure and atopy, according to the CD14 C-159T
      polymorphism.
AB  - BACKGROUND: A higher exposure to bacterial compounds is purported to explain the
      lower prevalence of allergy in farm children, but responsiveness to bacterial
      compounds is modulated by genetic factors. OBJECTIVE: To assess whether the
      protective effect of farm exposure on atopy is influenced by a CD14 promoter
      functional polymorphism. METHODS: We administered a detailed questionnaire on
      farm exposure in childhood and genotyped the CD14 C-159T polymorphism in 2 French
      centers participating in the European Community Respiratory Health Survey (ECRHS)
      II. RESULTS: Six hundred randomly selected young adults provided blood samples
      for IgE measurements and had CD14 C-159T genotyped. Exposure to a farming
      environment in early life was associated with a reduced risk of nasal allergies
      (odds ratio [OR], 0.54; 95% CI, 0.29-1.00) and atopic sensitization (OR, 0.47;
      95% CI, 0.24-0.93) in adulthood. A lower risk of allergic rhinitis and atopy was
      also observed in carriers of the CD14-159TT genotype compared with -159CC
      subjects (OR, 0.52; 95% CI, 0.30-0.88; and OR, 0.54; 95% CI, 0.31-0.92,
      respectively). When farm exposure and CD14 C-159T were considered together, the
      risk of nasal allergies and atopy was the most reduced in the subjects who
      combined both an early-life exposure to a farming environment and the -159TT
      genotype (OR, 0.26; 95% CI, 0.07-0.94; and OR, 0.21; 95% CI, 0.05-0.93,
      respectively, vs nonexposed -159CC+CT subjects). The results were consistent in
      the 2 centers, supporting the validity of the results. CONCLUSION: A gene-by
      environment interaction between CD14 C-159T and environmental exposure in
      childhood may modify the development of atopy. CLINICAL IMPLICATIONS: This
      polymorphism should be considered in interventions studies that use microbial
      stimuli to reduce sensitization.

PMID- 16950286
TI  - Prenatal initiation of endotoxin airway exposure prevents subsequent allergen
      induced sensitization and airway inflammation in mice.
AB  - BACKGROUND: New preventive strategies against the development of allergic
      diseases focus on potentially immunomodulatory components, such as bacterial
      LPSs. Optimal time frames for initiating immunomodulation to receive a sufficient
      effect against allergen sensitization are still unclear. OBJECTIVE: Using a mouse
      model, we investigated the influence of prenatal LPS exposure on later allergen
      mediated sensitization and airway inflammation in the offspring. METHODS:
      Pregnant BALB/c mice were repeatedly exposed to aerosolized LPS (LPS Escherichia
      coli; 3x per week, day 7 of gestation time up to delivery). Some of the offspring
      were further exposed to aerosolized LPS before allergen sensitization with
      ovalbumin (OVA; administered intraperitoneally day 28 up to day 42) and OVA
      airway challenges (days 56-58). Positive control animals were placebo exposed to
      PBS instead of LPS, and negative control animals were first placebo exposed and
      later placebo sensitized with PBS instead of OVA. RESULTS: Compared with positive
      control animals, prenatal LPS exposure suppressed (1) allergen-specific
      sensitization (IgE production), (2) eosinophilic airway inflammation (reduced
      numbers of eosinophils in bronchoalveolar lavage fluids), and (3) in vivo airway
      reactivity in response to methacholine. These effects occurred only when prenatal
      was combined with further postnatal LPS exposure. Suppression of allergen
      mediated inflammatory responses was associated with increased Toll-like receptor
      and T-bet expression by lung tissues and a shift toward predominantly T(H)1
      immune responses in spleen cells cultured with OVA in vitro. CONCLUSION: Prenatal
      initiated and postnatal sustained LPS exposure increased endotoxin susceptibility
      and prevented later allergen sensitization in offspring through inhibition of
      T(H)2 immune responses. CLINICAL IMPLICATIONS: Immunomodulation with bacterial
      compounds during gestation time might be an effective mode for first-step primary
      prevention against allergic diseases.

PMID- 16950287
TI  - Cat allergen level: its determinants and relationship to specific IgE to cat
      across European centers.
AB  - BACKGROUND: Cat allergen level in settled house dust and its determinants in
      Europe are unknown. OBJECTIVE: The aim of this study is to quantify the level of
      cat allergens in mattress dust, to study its determinants, and to analyze the
      relationship with cat specific IgE on community level across European centers.
      METHODS: Trained field workers collected dust from approximately 3000 mattresses
      during home visits in 22 European Community Respiratory Health Survey II centers.
      Sieved dust extracts were assayed for cat allergen using a mAb ELISA assay.
      RESULTS: The overall geometric mean cat allergen was 0.94 microg/g, ranging from
      0.12 microg/g in Huelva, Spain, to 3.76 microg/g in Antwerp, Belgium. Current cat
      owners' homes showed substantially higher levels than past cat owners' and never
      cat owners' homes (geometric mean and 95% CI, 61.4 microg/g [48.4-77.9] vs 1.37
      microg/g [0.97-1.9] vs 0.29 microg/g [0.27-0.31]). Community prevalence of cat
      ownership was moderately correlated with cat allergen levels in noncat owners
      (r(s) = 0.50), but not for past or current cat owners. The multilevel model
      identified community prevalence of cat keeping as the only statistically
      significant determinant of mattress cat allergen levels for noncat owners.
      However, averaged cat allergen levels per center were not related to community
      prevalence of detectable specific IgE to cat. CONCLUSION: Not having a cat in the
      home is associated with substantially lower Fel d 1 concentration, but does not
      protect against high Fel d 1 exposure in communities where cat ownership is
      common. CLINICAL IMPLICATIONS: People (including patients with cat allergy) who
      do not own cats may be exposed to high levels of cat allergen in their home,
      particularly if they live in communities with high levels of cat ownership.

PMID- 16950288
TI  - Distribution and determinants of house dust mite allergens in Europe: the
      European Community Respiratory Health Survey II.
AB  - BACKGROUND: Several studies in European homes have described allergen levels from
      the house dust mite species Dermatophagoides pteronyssinus and to a lesser extent
      Dermatophagoides farinae, but geographic comparisons of exposure levels and risk
      factors have been hampered by a lack of standardized methods. OBJECTIVE: To study
      the distribution and determinants of the major house dust mite allergens Der p 1
      and Der f 1 in 10 European countries using a common protocol. METHODS: During
      home visits with 3580 participants of the European Community Respiratory Health
      Survey II from 22 study centers, mattress dust was sampled and analyzed for Der p
      1, Der f 1, and Der 2 allergen. Information on housing characteristics was
      obtained by both observations and interview. RESULTS: Der 1 and Der 2 allergens
      were detectable (>/=0.1 mug/g) in 68% and 53% of the samples, respectively. Large
      differences in allergen levels between study centers were observed, and
      geographic patterns for Der p 1 and Der f 1 were different. Low winter
      temperatures reduced Der p 1 rather than Der f 1. Important risk factors for high
      allergen levels included an older mattress, a lower floor level of the bedroom,
      limited ventilation of the bedroom, and dampness for Der p 1 but not for Der f 1.
      CONCLUSION: There are large qualitative and quantitative differences of house
      dust mite allergen levels in Europe, which can partly be explained by geographic
      and housing characteristics. CLINICAL IMPLICATIONS: Mite allergen exposure may be
      reduced by replacing the mattress regularly and increasing ventilation of the
      bedroom, particularly in winter.

PMID- 16950289
TI  - Do asthma and allergy influence subsequent pet keeping? An analysis of childhood
      and adulthood.
AB  - BACKGROUND: Asthma and allergy might influence the choice of keeping pets,
      leading to apparent protective effects of pets on allergic disease. OBJECTIVE: We
      investigated the effects of asthma and allergy on subsequent pet keeping in
      childhood and adulthood. METHODS: Information about asthma and pet keeping at
      ages 0 to 4, 5 to 15, 20 to 44, and 26 to 56 years was provided by 9812 subjects
      participating in the 9-year follow-up of the European Community Respiratory
      Health Survey. RESULTS: In childhood asthma debut at younger than 5 years was
      associated with less cat keeping at 5 to 15 years (odds ratio [OR], 0.60; 95% CI,
      0.44-0.82), an effect only observed when the parents did not have asthma or
      allergy (P(interaction) = .045). Childhood asthma did not influence adult pet
      ownership, unless there were adult symptoms. Adults less often acquired cats at
      follow-up if they had 3 or more asthma symptoms (OR, 0.78; 95% CI, 0.64-0.95),
      were taking asthma medication (OR, 0.48; 95% CI, 0.31-0.74), had hay fever (OR,
      0.75; 95% CI, 0.62-0.91), had atopy (OR, 0.75; 95% CI, 0.61-0.91), or had
      specific IgE to cat (OR, 0.57; 95% CI, 0.39-0.82) at baseline. Adults who already
      had pets usually continued keeping the same type of pet, except that the presence
      of 3 or more asthma symptoms was associated with less subsequent dog keeping (OR,
      0.69; 95% CI, 0.53-0.89). Pet removal between surveys to reduce allergen was
      reported by 4.7%. CONCLUSION: Selective avoidance subsequent to asthma or allergy
      was observed for childhood cat keeping and adult cat acquisition. Avoidance would
      produce an apparent protective effect of cats on childhood asthma (large OR,
      0.83). Avoidance was generally not observed for dogs or birds. CLINICAL
      IMPLICATIONS: A part of the protective effects of childhood cats on asthma and
      allergy can be attributed to selective avoidance.

PMID- 16950290
TI  - Analysis of the burden of treatment in patients receiving an EpiPen for yellow
      jacket anaphylaxis.
AB  - BACKGROUND: Venom immunotherapy (VIT) is a treatment with established efficacy
      for the prevention of repeated anaphylactic reactions in patients with
      Hymenoptera allergy, which also allows patients to discontinue carrying an
      EpiPen. Despite their merits, both treatments can have negative aspects
      potentially important to patients. OBJECTIVE: We examined possible negative
      aspects of the EpiPen in comparison with VIT as perceived by patients. METHODS:
      Positive and negative aspects of both treatments were measured by using a burden
      of treatment questionnaire together with statements about the EpiPen. RESULTS:
      One hundred ninety-three patients were included, of whom 94 consented to
      randomization: 47 received VIT, and 47 received the EpiPen. Of the remaining 99,
      75 chose VIT, and 26 chose the EpiPen. Of the patients receiving VIT, 91.5% were
      (extremely) positive about their treatment, and 85% would choose VIT again. Of
      the patients receiving the EpiPen, only 48% were positive about their treatment,
      and even of these patients, 68% preferred to be treated with VIT after 1 year of
      carrying the EpiPen. Although most patients indicated that it is reassuring to
      carry an EpiPen and makes them feel safe, many patients also indicated that it is
      inconvenient and troublesome. Especially patients who were negative about the
      EpiPen indicated that they would not dare use the EpiPen if necessary and were
      afraid at possible side effects. CONCLUSION: In contrast to VIT, the EpiPen is
      perceived as burdensome by most patients with venom allergy. For most patients,
      an EpiPen is an unsuitable definitive treatment. CLINICAL IMPLICATIONS: As VIT
      enables patients with venom allergy to get rid of the EpiPen, patients should be
      offered VIT.

PMID- 16950291
TI  - Differential allergen sensitization patterns in chestnut allergy with or without
      associated latex-fruit syndrome.
AB  - BACKGROUND: Chestnut allergy has been almost exclusively considered in the
      context of the latex-fruit syndrome. Chestnut allergens not linked to latex
      hypersensitivity have not been studied. OBJECTIVE: We sought to explore whether
      differences in sensitization patterns between chestnut allergy with or without
      associated latex-fruit syndrome can be detected. METHODS: Twelve patients
      sensitized to chestnut but not to latex and 3 control patients with latex
      chestnut allergy were analyzed. A major chestnut allergen was purified and
      characterized. IgE immunoblotting, specific IgE determination, and skin prick
      tests with 5 isolated allergens involved in food allergy or latex-fruit syndrome
      were also performed. RESULTS: A major 9-kd allergen was detected in chestnut
      extract, isolated, and identified as lipid transfer protein (LTP) Cas s 8.
      Specific IgE to this allergen was found in 91% (by means of IgE immunoblotting)
      and 58% (by means of ELISA) of sera from patients with chestnut but not latex
      allergy. Moreover, 66% of these patients had positive skin prick test responses
      to Cas s 8. Additionally, allergenic LTPs from peach fruit and Artemisia vulgaris
      pollen were also reactive. In contrast, avocado class I chitinase and latex
      hevein, allergens associated with the latex-fruit syndrome, showed no reaction.
      The opposite situation was exhibited by patients with latex-chestnut allergy.
      CONCLUSIONS: Patients with chestnut allergy with or without associated latex
      hypersensitivity present different patterns of major allergens (LTPs and class I
      chitinases, respectively). CLINICAL IMPLICATIONS: LTPs and class I chitinases can
      be used as diagnostic tools in patients with chestnut allergy to predict whether
      an associated latex sensitization and a risk of potential cross-reactivity with
      other plant foods and pollens exist.

PMID- 16950292
TI  - Skin prick tests reveal stable and heritable reduction of allergenic potency of
      gene-silenced tomato fruits.
AB  - BACKGROUND: Today, for patients with food allergy, the only possibility to
      prevent allergic reactions is avoidance of the allergenic food. Genetic
      engineering of hypoallergenic plants by means of RNA interference (RNAi) could be
      an approach to improve the quality of life of subjects with food allergy.
      OBJECTIVES: We sought to achieve stable inhibition of expression of the
      allergenic nonspecific lipid transfer protein Lyc e 3 in tomato and to analyze
      the reduction of allergenicity in vitro by using histamine release assays and in
      vivo by using skin prick tests with transgenic tomato fruits. METHODS: Gene
      silencing was performed by means of RNAi and monitored by using Western blotting
      with nonspecific lipid transfer protein-specific antibodies and sera from
      patients with tomato allergy. Dose-dependent basophil histamine release assays,
      prick-to-prick skin testing, and determination of endogenous histamine content
      were performed with fruits harvested from plants of the first and second
      generation to assess the allergenic potency compared with that of wild-type
      fruits. RESULTS: We demonstrated that silencing of Lyc e 3 by means of RNAi
      contributes to reduced skin reactivity and is passed on to the next generation of
      fruits. A significant reduction of allergenic potency was determined in vitro and
      confirmed by using skin prick tests. CONCLUSION: Taken together, these results
      indicate that RNAi technology is an effective tool to generate foods with reduced
      allergenicity. CLINICAL IMPLICATIONS: Allergen-reduced plant foods might allow
      reduction of dietary restrictions for patients allergic to panallergen families.

PMID- 16950293
TI  - Peanut allergen exposure through saliva: assessment and interventions to reduce
      exposure.
AB  - BACKGROUND: Exposure to food allergens through saliva (kissing, utensils) can
      cause local and systemic allergic reactions. OBJECTIVE: To determine the time
      course of peanut allergen (Ara h 1) persistence in saliva after ingestion of
      peanut butter and to evaluate mouth cleansing interventions to reduce salivary
      peanut allergen. METHODS: Thirty-eight individuals ingested 2 tablespoons of
      peanut butter, and saliva was collected at various time points. At another time,
      samples were collected after 5 interventions (brushing teeth, brushing and
      rinsing, rinsing, waiting then brushing, waiting then chewing gum). Detection of
      Ara h 1 was performed by a monoclonal-based ELISA (detection limit, 15-20 ng/mL).
      RESULTS: Salivary Ara h 1 varied considerably immediately after ingestion, but
      included levels expected to invoke reactions (as much as 40 microg/mL). Most
      (87%) subjects with detectable peanut after a meal had undetectable levels by 1
      hour with no interventions. None had detectable levels several hours later after
      a peanut-free lunch. This result indicates (95% confidence) that 90% would have
      undetectable Ara h 1 in saliva under these circumstances. All of the
      interventions reduced salivary Ara h 1, in some cases by >95%, but Ara h 1
      remained detectable in approximately 40% of samples (though typically below
      thresholds reported to induce reactions). CONCLUSION: Patients with peanut
      allergy require counseling regarding risks of kissing or sharing utensils, even
      if partners have brushed teeth or chewed gum. Advice to reduce risks, though not
      as ideal as total avoidance, includes waiting a few hours plus eating a peanut
      free meal. CLINICAL IMPLICATIONS: Waiting several hours and ingesting a peanut
      free meal were more effective at reducing salivary peanut protein concentration
      than simple, immediate interventions.

PMID- 16950294
TI  - Hyperresponsive TH2 cells with enhanced nuclear factor-kappa B activation induce
      atopic dermatitis-like skin lesions in Nishiki-nezumi Cinnamon/Nagoya mice.
AB  - BACKGROUND: Nishiki-nezumi Cinnamon/Nagoya (NC/Nga) mice raised in nonair
      controlled conventional circumstances spontaneously develop atopic dermatitis
      like skin lesions; however, the underlying mechanisms remain unclear. OBJECTIVE:
      We wanted to identify the critical intracellular signaling molecules in T cells
      that induce atopic dermatitis-like skin legions in NC/Nga mice. METHODS: We
      examined the levels of signal transduction and cytokine production in T cells,
      particularly those in atopic dermatitis-like lesions induced by the topical
      injection of mite antigens in NC/Nga mice under specific pathogen-free
      conditions. RESULTS: In NC/Nga mice maintained under specific pathogen-free
      conditions, the capability of T(H)1/T(H)2 and T cytotoxic 1/T cytotoxic 2
      (Tc1/Tc2) cell differentiation increased significantly. T-cell antigen receptor
      mediated activation of the extracellular signal-regulated kinase/mitogen
      activated protein kinase cascade and nuclear factor-kappaB (NF-kappaB) signaling
      were enhanced in NC/Nga T cells. The expression of T(H)2 cytokines (IL-4, IL-13,
      and IL-5) and that of GATA-binding protein 3 (GATA3), avian musculoaponeurotic
      fibrosarcoma (c-Maf), NF-kappaB, and activator protein 1 (AP1) selectively
      increased in draining lymph node T cells of NC/Nga mice. Moreover, the cell
      transfer of inhibitory NF-kappaB mutant-infected T(H)2 cells reduced ear
      thickness in the mite antigen-induced skin lesion of NC/Nga mice. CONCLUSION:
      Hyperresponsive T(H)2 cells with an enhanced activity of NF-kappaB and AP1 play a
      crucial role in the pathogenesis of atopic dermatitis-like skin lesions in NC/Nga
      mice. CLINICAL IMPLICATIONS: These results indicate potential therapeutic
      usefulness of developing selective inhibitors for NF-kappaB in the treatment of
      human atopic dermatitis.

PMID- 16950295
TI  - Immunization with a low-dose replicon DNA vaccine encoding Phl p 5 effectively
      prevents allergic sensitization.
AB  - BACKGROUND: Replicase-based DNA vaccines stimulate T(H)1-biased immune responses
      at ultralow doses and induce self-removal of transfected cells through apoptosis.
      Both aspects are important requirements for efficient and safe DNA-based
      immunotherapy of type I allergies. OBJECTIVE: A Sindbis virus replicon-based DNA
      vaccine encoding the major timothy grass pollen allergen Phl p 5 was evaluated
      for its antiallergic potential compared with a conventional DNA vaccine in a
      BALB/c mouse model of allergy. METHODS: Mice were intradermally prevaccinated
      with plasmid DNA, followed by sensitization and intranasal allergen provocation
      with recombinant Phl p 5. In vitro proliferation and cytokine secretion was
      measured in splenocyte cultures. Distribution of IgG1, IgG2a, and IgE antibody
      subclasses was determined by means of ELISA. IgE-mediated degranulation was
      measured with the basophil release assay. Bronchoalveolar lavage fluid was
      analyzed for eosinophils, IL-4, IL-5, IL-13, and IFN-gamma. Mucus production,
      inflammatory infiltrates, and epithelial damage were determined in lung sections.
      RESULTS: Both vaccines induced T(H)1-biased immune responses, resulting in
      suppression of functional IgE, reduction of eosinophilia in bronchoalveolar
      lavage fluid, and alleviation of lung pathology. However, immunization with the
      replicon DNA vaccine elicited these effects at a 100-fold lower dose compared
      with the conventional DNA vaccine. CONCLUSIONS: The increased immunogenicity of
      replicon-based DNA vaccines allows for application of extremely low doses,
      thereby eliminating the concerns associated with conventional DNA vaccines, which
      have to be administered at milligram amounts to induce immune reactions in human
      subjects. CLINICAL IMPLICATIONS: Their high safety profile makes replicon-based
      DNA vaccines promising candidates for treatment of type I allergies in the
      clinic.

PMID- 16950296
TI  - Early-life domestic aeroallergen exposure and IgE sensitization at age 4 years.
AB  - BACKGROUND: Although it is widely assumed that childhood sensitization to common
      aeroallergens is directly related to allergen exposure in early life, few
      longitudinal studies have investigated this issue, and available data are scarce
      and mainly limited to high-risk groups. OBJECTIVE: We sought to assess the role
      of early exposure to 2 major household aeroallergens (Der p 1 and Fel d 1) in
      sensitization at the age of 4 years. METHODS: Pregnant women and their children
      were recruited for the Asthma Multicenter Infant Cohort Study. Three cohorts
      (Ashford in the United Kingdom and Menorca and Barcelona in Spain) followed the
      same research protocol. A total of 1611 newborn children were initially included
      in the cohort, from whose homes we collected dust samples at 3 months of age for
      1474; Der p 1 and Fel d 1 levels were measured. Of these children, we obtained
      blood for specific IgE determination in 1019. RESULTS: The risk of Fel d 1
      sensitization increased with exposure in a nonlinear manner. No association was
      found between specific IgE to Der p 1 and aeroallergen levels of exposure at
      early life in 2 centers, but a positive association was observed in the third.
      CONCLUSIONS: The dose-response relationships between allergen exposure and
      sensitization differ between allergens and might vary between different locales.
      The hypothesis that sensitization to house dust mite is directly related to
      levels of allergen exposure might not apply to the general population or to
      different ranges of exposure. CLINICAL IMPLICATIONS: Aeroallergen avoidance might
      not have any important effect on the incidence of sensitization.

PMID- 16950297
TI  - Identification of the Syk kinase inhibitor R112 by a human mast cell screen.
AB  - BACKGROUND: Activation of the IgE receptor, FcvarepsilonRI, in mast cells is the
      key mechanism initiating and propagating pathophysiological responses in allergic
      rhinitis. OBJECTIVE: Identify and characterize a small molecule inhibitor of IgE
      dependent mast cell activation for the treatment of allergic diseases. METHODS: A
      cell-based high-throughput screen for small molecules that block IgE signaling
      was performed in cultured human mast cells. A potent inhibitor, referred to as
      R112, was selected and characterized by using biochemical and cell-based assays.
      R112 effects on IgE-dependent degranulation and cytokine production was measured
      in mast cells and basophils and compared with other mast cell inhibitors.
      RESULTS: R112 inhibited degranulation induced by anti-IgE cross-linking in mast
      cells (tryptase release, effective concentration for 50% inhibition [EC(50)] =
      353 nmol/L) or basophils (histamine release, EC(50) = 280 nmol/L), and by
      allergen (dust mite) in basophils (histamine release, EC(50) = 490 nmol/L). R112
      also blocked leukotriene C4 production and all proinflammatory cytokines tested.
      Subsequent molecular characterization indicated that R112 is an ATP-competitive
      spleen tyrosine kinase (Syk) inhibitor (inhibitory constant [K(i)] = 96 nmol/L).
      Its onset of action was immediate, and the inhibition was reversible. Incubation
      of mast cells with R112 showed that cytokine production in mast cells was
      dependent on sustained activation of the FcvarepsilonRI-Lyn-spleen tyrosine
      kinase pathway. Unlike other mast cell inhibitors, R112 was able to completely
      inhibit all three IgE-induced mast cell functions: degranulation, lipid mediator
      production, and cytokine production. CONCLUSION: R112 potently, completely, and
      rapidly abrogated all mast cell activation cascades triggered by IgE receptor
      cross-linking. CLINICAL IMPLICATIONS: R112 and its analogues offer a new modality
      in the treatment of allergic rhinitis.

PMID- 16950298
TI  - Proinflammatory effects of IL-4 antagonism.

PMID- 16950299
TI  - Is the allergic rhinitis and its impact on asthma classification useful in daily
      primary care practice?

PMID- 16950300
TI  - Respirable trichothecene mycotoxins can be demonstrated in the air of
      Stachybotrys chartarum-contaminated buildings.

PMID- 16950301
TI  - Adverse reactions to fungal metabolic products in mold-contaminated areas.

PMID- 16950302
TI  - Position paper on molds is seriously flawed.

PMID- 16950303
TI  - The role of airborne mold in chronic rhinosinusitis.

PMID- 16950304
TI  - Adverse health effects of indoor mold exposure.

PMID- 16950305
TI  - How solid is the Academy position paper on mold exposure?

PMID- 16950306
TI  - Rigor, transparency, and disclosure needed in mold position paper.

PMID- 16950307
TI  - Nondisclosure of conflicts of interest is perilous to the advancement of science.

PMID- 16950312
TI  - Mechanisms of injury to the newborn brain.
AB  - Preterm and ill term infants are at risk for brain injury and subsequent
      neurodevelopmental delay as a result of many perinatal factors. Outlined in this
      article are the basic science mechanisms by which hypoxia, hypocapnia, and
      hypercapnia may result in neuronal injury in the newborn brain.

PMID- 16950313
TI  - The physiological basis for continuous electroencephalogram monitoring in the
      neonate.
AB  - Continuous monitoring of the electrocortical activity as compared with
      intermittent recording sessions offers a possibility of revealing changes of the
      condition of the brain, relevant for clinical decisions. Furthermore, trend
      monitoring, such as amplitude integrated electroencephalogram (aEEG), helps the
      clinician in extracting features such as background activity, sleep-waking
      cycling, and seizure patterns, which have been proven relevant for prognosis and
      treatment of the preterm and sick term infant. A coherent model for
      classification and description of neonatal aEEG patterns is presented.

PMID- 16950314
TI  - Brain monitoring in the neonate--the Rationale.
AB  - Experts argue that no brain monitoring of clinical value is currently available
      for the very preterm baby. Evidence is lacking about all parts of the therapeutic
      package: specificity and sensitivity for severe brain compromise, effectiveness
      of specific intervention, and overall clinical value over and above standard
      care. However, brain monitoring will probably be most important ultimately for
      establishing specific causation between modifiable factors and brain dysfunction
      or damage.

PMID- 16950315
TI  - Amplitude integrated electroencephalography in the full-term newborn.
AB  - Amplitude-integrated electroencephalography (aEEG) is beginning to play an
      important role in the care of full-term infants who have neonatal encephalopathy.
      The three main features an aEEG provides include (1) the background pattern,
      showing the activity at admission to the neonatal intensive care unit and the
      rate of recovery during the first 24 to 48 hours after birth; (2) the presence or
      absence of sleep-wake cycling; and (3) the presence of most electrographic
      discharges.

PMID- 16950316
TI  - Continuous electroencephalography monitoring of the preterm infant.
AB  - Continuous electroencephalography (EEG) monitoring provides clinically relevant
      information in preterm infants. Acute changes during development of
      intraventricular hemorrhage and white matter injury are associated with EEG and
      amplitude-integrated EEG (aEEG) deterioration. The early EEG background is also
      correlated with outcome in preterm infants, although other problems associated
      with prematurity may influence the long-term prognosis. The limitations of EEG
      monitoring should be well-understood by users and the continuous EEG monitor
      should be used as a complement to the standard EEG.

PMID- 16950317
TI  - Prolonged electroencephalogram monitoring for seizures and their treatment.
AB  - This article reviews the diagnosis of neonatal seizures using routine
      electroencephalogram (EEG) examinations and long-term EEG monitoring. EEG is
      considered the gold standard for identifying the presence and quantifying the
      burden of neonatal seizures. The most common medication used to treat neonatal
      seizures is phenobarbital, although its efficacy has never been demonstrated by a
      formal, randomized, placebo-controlled drug trial.

PMID- 16950318
TI  - Training neonatal staff in recording and reporting continuous
      electroencephalography.
AB  - Continuous electroencephalography can contribute useful information to clinical
      decision-making in neonatal care. Equipment is now reliable and user-friendly
      enough that its use can be taught to medical and nursing staff so that a 24-hour
      capability is achieved. It is possible to teach neonatologists, in a 1-day
      course, background knowledge on EEG and amplitude-integrated EEG (aEEG),
      recognition of aEEG patterns that have clinical significance, recognition of
      seizures using aEEG and "raw" EEG, the essentials of electrode placement for
      aEEG, and interpretation of findings in the clinical context. This must be
      followed up by background reading, frequent peer-review sessions on EEG
      recordings, and a reliable system for storing and access, as well as willingness
      to consult experienced operators elsewhere.

PMID- 16950319
TI  - High-density electroencephalogram monitoring in the neonate.
AB  - Early diagnosis of neurologic conditions is crucial for successful early
      intervention; therefore, minimally invasive diagnostic procedures are invaluable
      during the neonatal period. The clinical usefulness of one such technique, the
      electroencephalogram (EEG), is well documented. However, the advent of high
      density recording systems has extended its application. High-density EEG
      recording uses a significantly increased number of recordings sites: 128 to 256
      electrodes compared with 10 to 30 in standard recording systems. This report
      describes the benefits of using more electrode sites and highlights the use of
      related procedures for the assessment of neural integrity across sensory
      modalities.

PMID- 16950320
TI  - Sleep and brain development.
AB  - Historically, researchers studying the field of sleep have been divided into two
      main groups. The first group of sleep studies was based on behaviors and
      behavioral sleep. The second group of researchers based their studies on
      electroencephalogram EEG patterns and changes. With technologic advancements, a
      third group of researchers is studying sleep using active brain-imaging
      techniques. Most events that are seen on brain imaging correlate with the EEG
      pattern, so that they relate to each other in time and state. Unfortunately,
      behavioral states do not correlate necessarily with the EEG changes and vary
      greatly between animal species. This article focuses on sleep stages and
      behaviors that are associated with characteristic EEG patterns.

PMID- 16950321
TI  - Near-infrared spectroscopy in the fetus and neonate.
AB  - Near-infrared spectroscopy allows for real-time, noninvasive measurement of
      cerebral hemodynamics and oxygenation at the bed-side. This article describes
      animal and clinical research using near-infrared spectroscopy to study cerebral
      hemodynamic function in the fetus, neonate, and child.

PMID- 16950322
TI  - Mass spectrometry in neonatal medicine and clinical diagnosis--the [corrected]
      potential use of mass spectrometry in neonatal brain [corrected] monitoring.
AB  - This article discusses the application of mass spectroscopy, a technology that
      may have great potential for screening neonatal brain injury. This approach is
      anticipated to become increasingly important in neonatal and perinatal research
      and newborn care during the next few years.

PMID- 16950323
TI  - Characterization of recovery profiles using gas chromatography-triple quadrupole
      mass spectrometry for the determination of pesticide residues in meat samples.
AB  - The assessment of the recovery factor with the analyte concentration in meat
      samples has been studied for the determination of organochlorine and
      organophosphorus pesticides in meat by gas chromatography-triple quadrupole mass
      spectrometry (GC-MS/MS). For that purpose, recent IUPAC recommendations, which
      distinguishes between two terms, recovery factor and apparent recovery, have been
      followed. Besides, the systematic error due to the matrix effect has been
      evaluated by a new term recently proposed, calibration recovery. Recovery
      profiles were obtained analyzing spiked blank matrix, where the analytes were
      added before and after the extraction procedure. In a first step, the
      quantification of the compounds was carried out using a solvent calibration
      curve. The systematic errors due to the matrix effect during the quantification
      step and the error due to the sample treatment have been evaluated. Both apparent
      and calibration recovery components depend on the actual analyte concentration in
      the sample while the recovery factor remains constant except for analyte
      concentration close to quantification limit. In addition, the concentration
      limits, from which an acceptable recovery value (70-110%) can be obtained, are
      given. If spiked samples are quantified by matrix-matched calibration, the matrix
      effect is minimized and the calibration recovery component is 100%, and apparent
      recovery only depends on the recovery factor. The obtained values indicate
      recovery factor does not depend on the analyte concentration, except for those
      values closed to quantification limit.

PMID- 16950324
TI  - Single drop liquid-liquid-liquid microextraction of methamphetamine and
      amphetamine in urine.
AB  - Single drop liquid-liquid-liquid microextraction (LLLME) combined with high
      performance liquid chromatography (HPLC)-UV detection was investigated for the
      determination of a popular drug of abuse, methamphetamine (MAP), and its major
      metabolite, amphetamine (AP), in urine samples. The target compounds were
      extracted from NaOH modified sample solution to a thin layer of organic solvent
      membrane, and back-extracted to an acidic acceptor drop suspended on the tip of a
      50-microL HPLC syringe in the aforementioned organic layer. This syringe was also
      used for direct injection after extraction. Factors affecting extraction
      efficiency were studied. At optimal conditions, the overall enrichment factor
      (EF) was 500-fold for AP and 730-fold for MAP, respectively. The method exhibited
      a wide linear range (1.0-1500 microg/L), low detection limit (0.5 microg/L), and
      good repeatability (RSD<5.0%) for both analytes. The feasibility of the method
      was demonstrated by the analysis of human urine samples.

PMID- 16950325
TI  - Polyethyleneimine precipitation versus anion exchange chromatography in
      fractionating recombinant beta-glucuronidase from transgenic tobacco extract.
AB  - Tobacco has been studied as a possible host for the production of recombinant
      proteins. In this report, recombinant beta-glucuronidase (rGUS) was used as a
      model protein to study the feasibility of using polyethyleneimine (PEI)
      precipitation to fractionate acidic recombinant proteins from transgenic tobacco.
      Results showed that rGUS was preferentially precipitated when the PEI dosage was
      beyond 200mg PEI/g total protein. At 700-800 mg PEI/g total protein, nearly 100%
      rGUS was precipitated with less than 40% native tobacco proteins co-precipitated.
      Approximately 85-90% of the rGUS activity could be recovered from the
      precipitation pellet for an enrichment ratio of 2.7-3.4. As a comparison, anion
      exchange chromatography (AEX) yielded similar results to PEI precipitation with
      66-90% rGUS activity recovered and an enrichment ratio of 1.8-3.1. The rGUS was
      further purified by an additional hydrophobic interaction chromatographic (HIC)
      step after precipitation or AEX. Similar results in terms of rGUS activity
      recovered and enrichment were obtained. The major interfering protein at the end
      of all purification steps is most likely the Fraction 1 protein ribulose 1,5
      bisphosphate carboxylase-oxygenase (Rubisco). The presence of this protein is
      likely the cause for the varying and somewhat low enrichment ratios, but it may
      be later removed via a size-exclusion chromatography step. PEI precipitation
      offers the advantage of allowing significant sample concentration prior to
      subsequent purification techniques such as chromatography and is much less
      expensive than chromatographic methods as well. Through direct comparison, this
      study shows that PEI may be used as an initial fractionation step in replacement
      of AEX to facilitate the purification of acidic recombinant proteins from
      transgenic tobacco.

PMID- 16950326
TI  - Solvation of the Whelk-O1 chiral stationary phase: a molecular dynamics study.
AB  - Density functional theory calculations and molecular dynamics simulations are
      employed to explore the solvation of the Whelk-O1 chiral stationary phase. First,
      a semi-flexible representation of the Whelk-O1 selective molecule is extracted
      from an extensive series of B3LYP/6-311+ G(2d,p) calculations. The resulting
      model is used to build a chiral surface, including end-caps, for molecular
      dynamics study of the interface between solvent and Whelk-O1. Three solvent
      environments in common use for Whelk-O1 HPLC have been examined: a normal-phase
      solvent of n-hexane/2-propanol; a reversed-phase solvent of water/methanol; and a
      supercritical solvent of CO(2) and methanol. In each case, we analyze the
      interface with an emphasis on solvent composition and solvent hydrogen bonding to
      the Whelk-O1 selector.

PMID- 16950327
TI  - Rapid gas chromatographic method for the determination of famoxadone,
      trifloxystrobin and fenhexamid residues in tomato, grape and wine samples.
AB  - Trifloxystrobin, fenhexamid and famoxadone belong to the generation of fungicides
      acting against a broad spectrum of fungi and widely used in Integrated Pest
      Management strategies in different agricultural crops but mainly in viticulture.
      In the present work, a gas chromatographic (GC) method for their determination
      was developed and validated on tomato, grape and wine matrices. The method was
      based on a simple one step liquid-liquid microextraction with
      cyclohexane/dichloromethane (9+1, v/v) and determination of fungicides by gas
      chromatography with nitrogen phosphorous (NP-) and electron capture (EC-)
      detection, and ion trap mass spectrometry (ITMS) for confirmation. The method was
      validated by recovery experiments, assessment of matrix effect and calculation of
      the associated uncertainty. Recoveries for GC-NPD and GC-ECD were found in the
      range of 81-102% with RSD <12%, while matrix-matched calibration solutions were
      imposed for quantification. LOQs ranged from 0.005 to 0.05 mg/kg and 0.01 to 0.10
      mg/kg for the GC-ECD and GC-NPD, respectively, depending on the sensitivity of
      each compound with trifloxystrobin being the most sensitive. The expanded
      uncertainty, calculated for a sample concentration of 0.10 mg/kg, ranged from 4.8
      to 13% for the GC-ECD and from 5.4 to 29% for the GC-NPD. The concentration
      levels for famoxadone residues found in tomato and grape samples from field
      experiments were clearly below the EU established MRL values, thus causing no
      problems in terms of food safety.

PMID- 16950328
TI  - Gas chromatography-mass spectrometry following microwave distillation and
      headspace solid-phase microextraction for fast analysis of essential oil in dry
      traditional Chinese medicine.
AB  - In this paper, a novel method based on gas chromatography-mass spectrometry (GC
      MS) following microwave distillation-headspace solid-phase microextraction (MD-HS
      SPME) was developed for the determination of essential oil in dry traditional
      Chinese medicine (TCM). TCM is dried before being preserved and used, there is
      too little water to absorb microwave energy and heat the TCM samples. In the
      work, carbonyl iron powders (CIP) was added and mixed with the dried TCM sample,
      which was used as microwave absorption solid medium for dry distillation of the
      TCM. At the same time, SPME was used for the extraction and concentration of
      essential oil after MD. The dry rhizomes of Atractylodes lancea DC was used as
      the model TCM, and used in the study. The MD-HS-SPME parameters including fiber
      coating, microwave power, irradiation time, and the amount of added CIP, were
      studied. To demonstrate the method feasibility, the conventional HS-SPME method
      was also used for the analysis of essential oil in the TCM. Experimental results
      show that more compounds were isolated and identified by MD-HS-SPME than those by
      HS-SPME. Compared to conventional HS-SPME, the advantages of the proposed method
      are: short extraction time and high extraction efficiency. All experimental
      results show that the proposed method is an alternative tool for fast analysis of
      essential oils in dry TCMs.

PMID- 16950329
TI  - The effect of a therapy dog on the communication skills of an adult with aphasia.
AB  - Little evidence-based research has been published within the field of
      communication disorders on the role of dogs as catalysts for human communication.
      This single participant study, a point of entry into this realm of research,
      explores the effects of a therapy dog on the communication skills of a patient
      with aphasia receiving intensive speech and language therapy within a
      rehabilitation setting. The researchers conclude that the presence of the dog
      does have the potential to stimulate both overt social-verbal and social
      nonverbal communication. LEARNING OUTCOMES: As a result of this activity the
      reader will be able to (1) describe the beneficial role of dogs to serve as
      catalysts for human communication (2) describe ways in which a person with
      aphasia may be assisted by a therapy dog and (3) become familiar with an animal
      assisted therapy (AAT) program set-up for patients with communication disorders
      within a rehabilitation setting.

PMID- 16950330
TI  - Is acquired short QT due to digitalis intoxication responsible for malignant
      ventricular arrhythmias?

PMID- 16950331
TI  - Noninvasive electrocardiographic imaging of cardiac resynchronization therapy in
      patients with heart failure.
AB  - Cardiac resynchronization therapy (CRT) using biventricular (BiV) pacing has been
      developed to restore synchrony and improve cardiac performance in patients with
      heart failure. It has been clinically beneficial in 65% to 70% of patients. Being
      an electrical (pacing) approach, detailed electrical information during CRT is
      critical in understanding its mechanism and clinical outcome. However, electrical
      data from patients have been limited because of the requirement for invasive
      mapping. Electrocardiographic imaging provides the necessary tool to
      noninvasively obtain this information. We applied electrocardiographic imaging to
      8 patients undergoing CRT during their native rhythm and various (single
      ventricular and BiV) pacing modes with the following observations: (1) native
      rhythm activation was heterogeneous with latest activation in lateral left
      ventricular (LV) base (3 of 6 patients) or in anterolateral, midlateral, or
      inferior LV; (2) when accompanied by fusion, LV pacing was as effective as BiV;
      (3) right ventricular pacing was not effective for resynchronization; (4)
      efficacy of CRT depended strongly on patient-specific electrophysiologic
      substrate.

PMID- 16950332
TI  - Integration of cardiac imaging and electrophysiology during catheter ablation
      procedures for atrial fibrillation.
AB  - As nonpharmacologic therapies for atrial fibrillation expand, the complexity of
      the anatomical and electrical substrates of atrial fibrillation requires
      integration of multiple imaging modalities for successful treatment. Combining
      chamber-specific imaging and electrophysiologic data points during ablation
      therapy has improved pulmonary vein isolation accuracy while diminishing risk.
      Merging 3-dimensional computed tomography left atrial renditions, intracardiac
      echocardiography, and electroanatomical mapping during pulmonary vein isolation
      is a reality that relates the complex anatomy of the left atrium to its often
      variable electrical targets. Direct visualization of radiofrequency lesion
      formation as well as electrode-tissue contact during current delivery has been
      accomplished in animal models using ultrasound and infrared imaging tools. The
      combination of these early integrative stepping stones may lead to imaging with
      real-time feedback relating tissue desiccation to electrical effect and lesion
      transmurality. Atrial fibrillation ablation outcome will improve as the
      electrophysiology laboratory continues to integrate real-time 3-dimensional
      cardiac chamber and tissue images before, during, and after radiofrequency or
      cryoablation of specific electrophysiologic targets.

PMID- 16950333
TI  - Evaluation of computerized interpretation of the pediatric electrocardiogram.
AB  - The purpose of this research was to determine the frequency and factors affecting
      disagreement between pediatric cardiologist (MD1 or MD2) and the computer
      assisted interpretation (CAI) of pediatric electrocardiograms from patients with
      heart disease (HD, n = 586) or normal heart (n = 561). Significant disagreement
      was found in HD (146/586, 25%) compared with normal heart (64/561, 11%) (P <
      .001). The CAI overinterpreted prolonged QT, sinus rhythm with ectopy, and right
      ventricular hypertrophy; CAI underinterpreted sinus rhythm, sinus arrhythmia, and
      right bundle branch block (P < .05). Increased disagreement was independently
      associated with HD (odds ration [OR], 2.2), younger patient age at the time of
      the electrocardiogram, if the computer interpretation had more than 3 separate
      diagnostic statements (OR, 3.2) and if the overreading cardiologist was MD1 (OR,
      2.9). Although CAI is helpful, pediatric cardiologists were more likely to
      disagree with the computer in rhythm diagnosis, recognition of bundle branch
      block, hypertrophy, and QT interval analysis.

PMID- 16950334
TI  - Importance of sterols acquired through host feeding in synovigenic parasitoid
      oogenesis.
AB  - Eupelmus vuilleti (Hymenoptera; Eupelmidae) is a host feeding ectoparasitoid of
      fourth-instar larvae or pupae of Callosobruchus maculatus (Coleoptera; Bruchidae)
      infecting Vigna unguiculata seed and pods (Fabacae). Parasitoid females are
      synovigenic, i.e. they are born with immature eggs and need to feed from the host
      in order to sustain egg production. In this study, the role of sterols obtained
      through host feeding in parasitoid oogenesis are examined. Quantitative and
      qualitative analyses of the sterol contents in each partner of the tritrophic
      interaction show that a parasitoid female's larval sterol contents is sufficient
      to produce only 30% of the total number of eggs laid throughout a female's life
      cycle. In a second step, by manipulating the composition of the sterols hemolymph
      in the host, it is shown that cholesterol obtained through adult nutrition plays
      a crucial role in the eggs viability but does not affect the egg production
      quantitatively. This result has important implications for understanding both the
      nutrient allocation strategy in this species and the impact of cholesterol in
      parasitoid reproduction.

PMID- 16950335
TI  - A call for transparency at the Global Fund.

PMID- 16950336
TI  - UN peacekeepers in Haiti.

PMID- 16950337
TI  - Stem-cell "breakthrough": much heat, little light.

PMID- 16950338
TI  - Getting it right for children: a review of UNICEF joint health and nutrition
      strategy for 2006-15.

PMID- 16950339
TI  - Altered fractionation: a fractional benefit?

PMID- 16950340
TI  - Inhibiting toll-like receptors in inflammatory disease.

PMID- 16950341
TI  - Radical nephrectomy: too radical for small renal masses?

PMID- 16950342
TI  - Community-acquired MRSA: can we control it?

PMID- 16950343
TI  - What's in a name? New glaucoma drugs.

PMID- 16950344
TI  - Phase I clinical trials: a call for papers.

PMID- 16950345
TI  - Pluto left out in the cold.

PMID- 16950348
TI  - Is there an Iraq war syndrome?

PMID- 16950349
TI  - Post-traumatic stress disorder in UK and US forces deployed to Iraq.

PMID- 16950351
TI  - Interpreting symptoms in military personnel after combat.

PMID- 16950353
TI  - Mental health of Iraqi children.

PMID- 16950354
TI  - Timing of umbilical cord clamping.

PMID- 16950356
TI  - Sex work during the World Cup in Germany.

PMID- 16950357
TI  - Early umbilical cord clamping and cord-blood banking.

PMID- 16950358
TI  - Sex work during the World Cup in Germany.

PMID- 16950359
TI  - Nuclear transfer to prevent mitochondrial DNA diseases.

PMID- 16950360
TI  - Health needs of older prisoners.

PMID- 16950361
TI  - Smart bombs are not enough.

PMID- 16950362
TI  - Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta
      analysis.
AB  - BACKGROUND: Several trials have studied the role of unconventional fractionated
      radiotherapy in head and neck squamous cell carcinoma, but the effect of such
      treatment on survival is not clear. The aim of this meta-analysis was to assess
      whether this type of radiotherapy could improve survival. METHODS: Randomised
      trials comparing conventional radiotherapy with hyperfractionated or accelerated
      radiotherapy, or both, in patients with non-metastatic HNSCC were identified and
      updated individual patient data were obtained. Overall survival was the main
      endpoint. Trials were grouped in three pre-specified categories:
      hyperfractionated, accelerated, and accelerated with total dose reduction.
      FINDINGS: 15 trials with 6515 patients were included. The median follow-up was 6
      years. Tumours sites were mostly oropharynx and larynx; 5221 (74%) patients had
      stage III-IV disease (International Union Against Cancer, 1987). There was a
      significant survival benefit with altered fractionated radiotherapy,
      corresponding to an absolute benefit of 3.4% at 5 years (hazard ratio 0.92, 95%
      CI 0.86-0.97; p=0.003). The benefit was significantly higher with
      hyperfractionated radiotherapy (8% at 5 years) than with accelerated radiotherapy
      (2% with accelerated fractionation without total dose reduction and 1.7% with
      total dose reduction at 5 years, p=0.02). There was a benefit on locoregional
      control in favour of altered fractionation versus conventional radiotherapy (6.4%
      at 5 years; p<0.0001), which was particularly efficient in reducing local
      failure, whereas the benefit on nodal control was less pronounced. The benefit
      was significantly higher in the youngest patients (hazard ratio 0.78 [0.65-0.94]
      for under 50 year olds, 0.95 [0.83-1.09] for 51-60 year olds, 0.92 [0.81-1.06]
      for 61-70 year olds, and 1.08 [0.89-1.30] for over 70 year olds; test for trends
      p=0.007). INTERPRETATION: Altered fractionated radiotherapy improves survival in
      patients with head and neck squamous cell carcinoma. Comparison of the different
      types of altered radiotherapy suggests that hyperfractionation has the greatest
      benefit.

PMID- 16950363
TI  - Therapeutic efficacy and safety of chaperonin 10 in patients with rheumatoid
      arthritis: a double-blind randomised trial.
AB  - BACKGROUND: Chaperonin 10 (heat shock protein 10, XToll) has anti-inflammatory
      properties related to the inhibition of Toll-like receptor signalling pathways.
      Our aim was to establish whether chaperonin 10 is safe and effective in the
      treatment of rheumatoid arthritis. METHODS: In this randomised, double-blind,
      multicentre study, 23 patients with moderate to severe active rheumatoid
      arthritis receiving disease-modifying antirheumatic drugs were randomly allocated
      to three treatment groups receiving intravenous chaperonin 10 twice weekly for 12
      weeks at doses of 5 mg (n=8), 7.5 mg (8), or 10 mg (7). The primary outcomes were
      change in disease activity score (DAS28) and improvement of core disease measures
      (American College of Rheumatology response score) from baseline to week 12. All
      analyses were done by intention to treat. This study is registered with the
      Australian Clinical Trials Registry, number ACTRNO12606000041550. FINDINGS:
      Primary endpoint measures improved from day 14 in all groups and continued to
      improve to day 84. By end of study, a 20% improvement of core disease measures
      was seen in six (86%, 95% CI 43-100), a 50% improvement in four (57%, 14-86), and
      a 70% improvement in two (29%, 0-57) patients given the highest dose of
      chaperonin 10. Clinical remission (as defined by a DAS28 <2.6) was achieved in
      three (13%) of 23 patients. Three individuals dropped out during the study: one
      in the 5 mg group (rheumatoid arthritis not controlled), one in the 7.5 mg group
      (adverse event), and one in the 10 mg group (lost to follow-up). The most common
      adverse events were exacerbation of rheumatoid arthritis (both during and after
      the study) and upper respiratory tract infection. Only one adverse event was
      judged to be of severe intensity. INTERPRETATION: Chaperonin 10 seems to be well
      tolerated and efficacious in treatment of the symptoms of rheumatoid arthritis,
      at least in the short term.

PMID- 16950364
TI  - Human rights abuse and other criminal violations in Port-au-Prince, Haiti: a
      random survey of households.
AB  - BACKGROUND: Reliable evidence of the frequency and severity of human rights
      abuses in Haiti after the departure of the elected president in 2004 was scarce.
      We assessed data from a random survey of households in the greater Port-au-Prince
      area. METHODS: Using random Global Positioning System (GPS) coordinate sampling,
      1260 households (5720 individuals) were sampled. They were interviewed with a
      structured questionnaire by trained interviewers about their experiences after
      the departure of President Jean-Bertrand Aristide. The response rate was 90.7%.
      Information on demographic characteristics, crime, and human rights violations
      was obtained. FINDINGS: Our findings suggested that 8000 individuals were
      murdered in the greater Port-au-Prince area during the 22-month period assessed.
      Almost half of the identified perpetrators were government forces or outside
      political actors. Sexual assault of women and girls was common, with findings
      suggesting that 35,000 women were victimised in the area; more than half of all
      female victims were younger than 18 years. Criminals were the most identified
      perpetrators, but officers from the Haitian National Police accounted for 13.8%
      and armed anti-Lavalas groups accounted for 10.6% of identified perpetrators of
      sexual assault. Kidnappings and extrajudicial detentions, physical assaults,
      death threats, physical threats, and threats of sexual violence were also common.
      INTERPRETATION: Our results indicate that crime and systematic abuse of human
      rights were common in Port-au-Prince. Although criminals were the most identified
      perpetrators of violations, political actors and UN soldiers were also frequently
      identified. These findings suggest the need for a systematic response from the
      newly elected Haitian government, the UN, and social service organisations to
      address the legal, medical, psychological, and economic consequences of
      widespread human rights abuses and crime.

PMID- 16950365
TI  - Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a
      public-health threat.
AB  - Staphylococcus aureus is a gram-positive bacterium that colonises the skin and is
      present in the anterior nares in about 25-30% of healthy people. Dependent on its
      intrinsic virulence or the ability of the host to contain its opportunistic
      behaviour, S aureus can cause a range of diseases in man. The bacterium readily
      acquires resistance against all classes of antibiotics by one of two distinct
      mechanisms: mutation of an existing bacterial gene or horizontal transfer of a
      resistance gene from another bacterium. Several mobile genetic elements carrying
      exogenous antibiotic resistance genes might mediate resistance acquisition. Of
      all the resistance traits S aureus has acquired since the introduction of
      antimicrobial chemotherapy in the 1930s, meticillin resistance is clinically the
      most important, since a single genetic element confers resistance to the most
      commonly prescribed class of antimicrobials--the beta-lactam antibiotics, which
      include penicillins, cephalosporins, and carbapenems.

PMID- 16950366
TI  - Pandemic influenza preparedness in the Asia-Pacific region.
AB  - Concerns are mounting that the threat of another influenza pandemic will become a
      reality and that the epicentre of the outbreak could be the Asia-Pacific region.
      We assessed the documents that some Asia-Pacific countries have published as part
      of preparedness planning for an outbreak of influenza in people. Regional
      approaches were polarised. Thailand, China, and Vietnam had set out a strategic
      vision to strengthen future capacity in preparedness planning. By contrast, Hong
      Kong, Australia, and New Zealand took a strategic approach aimed mainly at
      harnessing available resources or preparing for the deployment of resources such
      as stockpiled antiviral agents and vaccines. The plans of Hong Kong, Australia,
      and New Zealand compared favourably with the best European plans. The plans of
      resource-poor countries addressed some issues that were largely neglected by most
      European plans. Other countries (including those that do not yet have plans)
      could benefit from analysis of the strengths and weaknesses of the plans drawn up
      by countries in the region and in Europe.

PMID- 16950367
TI  - Deprivation in the desert: a case report from central Australia.

PMID- 16950368
TI  - Molecular insights from a novel cardiac troponin I mouse model of familial
      hypertrophic cardiomyopathy.
AB  - Gene mutations in cardiac troponin I (cTnI) account for up to 5% of genotyped
      families with familial hypertrophic cardiomyopathy (FHC). Little is known about
      how cTnI mutations cause disease. Five lines of transgenic mice were generated
      which overexpress the human disease-causing cTnI gene mutation, Gly203Ser
      (designated cTnI-G203S), in a cardiac-specific manner. Mice were compared to
      transgenic mice that overexpress normal cTnI (cTnI-wt) and non-transgenic
      littermates (NTG). cTnI-G203S mice developed all the characteristic features of
      FHC by age 21 weeks. Left ventricular hypertrophy was observed on
      echocardiography (1.25+/-0.05 mm vs. 0.86+/-0.02 mm in cTnI-wt, P<0.01),
      associated with a significant 4-fold increase in RNA markers of hypertrophy, ANF
      and BNP. Myocyte hypertrophy, myofiber disarray and interstitial fibrosis were
      observed in cTnI-G203S mice. Expression of the cTnI-G203S mutation in neonatal
      cardiomyocytes resulted in a significant increase in myocyte volume, and reduced
      interactions with both troponins T and C. Ca2+ cycling was abnormal in adult
      cardiomyocytes extracted from cTnI-G203S mice, with a prolonged decay constant in
      Ca2+ transients and a reduced decay constant in response to caffeine treatment.
      Mice with the cTnI-G203S gene mutation develop all the phenotypic features of
      human FHC. The cTnI-G203S mutation disrupts interactions with partner proteins,
      and results in intracellular Ca2+ dysregulation early in life, suggesting a
      pathogenic role in development of FHC.

PMID- 16950369
TI  - Electrical pacing counteracts intrinsic shortening of action potential duration
      of neonatal rat ventricular cells in culture.
AB  - Previous studies have demonstrated the relationship between the functional
      electrophysiological properties of cultured neonatal rat ventricular myocytes
      (NRVMs) and the ability of the substrate to induce and sustain arrhythmia. The
      goal of this study was to examine the effects of chronic pacing at a constant
      rate akin to that in vivo, on the functional electrophysiological properties of
      NRVM monolayers. Confluent NRVM monolayers grown on 20 mm diameter cover slips
      were left either unpaced or were stimulated at 3 Hz for the duration of the
      culture, and were optically mapped on days 4, 6, or 8. Action potential duration
      at 80% repolarization (APD80), conduction velocity (CV), and Kv4.3 (Ito) and NCX
      protein expression were measured. The effects of the excitation-contraction
      uncoupler 2,3-butadione monoxime (BDM) were also investigated. The 2 Hz APD80 of
      non-paced monolayers decreased significantly on days 6 (137.1+/-13.9 ms) and 8
      (109.8+/-9.0 ms) compared with day 4 (197.0+/-11.8 ms), while that of paced
      monolayers did not (206.8+/-9.7, 209.1+/-9.2, and 210.6+/-9.9 ms, respectively).
      The 2 Hz CV of non-paced monolayers increased significantly on days 6 (26.0+/-1.6
      cm/s) and 8 (26.5+/-1.0 cm/s) compared with day 4 (20.0+/-1.0 cm/s), while that
      of paced monolayers did not change significantly (26.0+/-2.0, 26.0+/-1.0, and
      23.8+/-1.2 cm/s, respectively). The restitution curves of APD80 and CV of paced
      monolayers were also unchanging from days 4 through 8. Despite the unchanging
      APD80 and CV, a decrease in Kv4.3 expression and an increase in NCX expression
      were observed in paced compared with non-paced monolayers. Cessation of pacing or
      administration of BDM caused a reversal of phenotype back to that of non-paced
      monolayers. In summary, chronic electrical stimulation of confluent NRVM
      monolayers results in stabilization of APD80 and an advancement of the
      developmental rise of CV that is mediated by electromechanical coupling. These
      effects produce a steadier functional phenotype that may be beneficial for
      electrophysiological studies.

PMID- 16950370
TI  - Evolution of telepsychiatry to rural sites: changes over time in types of
      referral and in primary care providers' knowledge, skills and satisfaction.
AB  - INTRODUCTION: Rural populations remain underserved in terms of psychiatric
      services. This study assesses changes over time in the utilization of
      telepsychiatric services by individual primary care providers (PCPs) and clinics
      in rural areas, specifically: (a) types of referrals for telepsychiatry service;
      (b) PCPs' knowledge and skills related to medication dosing; and (c) PCPs'
      satisfaction with telepsychiatry. METHODS: Data with regard to patient
      demographics, diagnoses, reason for consultation, medication dosing and
      satisfaction were prospectively collected on the first 200 and the subsequent 200
      telepsychiatric initial consultations. A number of educational interventions were
      implemented during the project. RESULTS: Adult patients were primarily referred
      for mood and anxiety disorders, particularly for diagnosis and medication
      treatment planning. Over time, PCPs significantly improved medication dosing and
      asked for more treatment planning help. PCPs' satisfaction also improved over
      time. DISCUSSION: Telepsychiatric consultation, in combination with specific
      educational interventions, appears to facilitate the enhancement of skills and
      knowledge of PCPs. "Developmental" steps in provider and clinic evolution, along
      with interventions specific to a given provider's and a given site's needs, ought
      to be further elucidated.

PMID- 16950372
TI  - Influence of patient preference and primary care clinician proclivity for
      watchful waiting on receipt of depression treatment.
AB  - OBJECTIVE: We examined whether patients' preference for watchful waiting and
      their primary care clinician's proclivity for watchful waiting were associated
      with decreased likelihood of receiving depression treatment. METHODS: In a
      quality improvement intervention for depression in primary care, patients with
      depressive symptoms were identified through screening in 46 clinics from June
      1996 to March 1997. We analyzed baseline survey data completed by clinicians and
      patients using logistic regression models. RESULTS: Of 1140 patients, 179 (16%)
      preferred watchful waiting over active treatment. After controlling for
      covariates, patients with depressive disorders who preferred watchful waiting
      were less likely to report use of antidepressants (OR=0.86, 95% CI=0.77-0.95).
      Among patients with depressive symptoms only, those who preferred watchful
      waiting were less likely to report antidepressant use (OR=0.84, 95% CI=0.76-0.93)
      or counseling (OR=0.84, 95% CI=0.77-0.95). Patients with less knowledge about
      depression were less likely to receive depression treatment. Clinician proclivity
      for watchful waiting was not associated with the likelihood that patients
      received depression treatment. CONCLUSIONS: Patient preference for watchful
      waiting is associated with lower rates of some depression treatments, especially
      among patients with subsyndromal depression. Addressing patient preference for
      watchful waiting in primary care may include active symptom monitoring and
      patient education.

PMID- 16950371
TI  - Outcome of new benzodiazepine prescriptions to older adults in primary care.
AB  - OBJECTIVE: The objective of this study was to examine the indications for
      benzodiazepine use, and the baseline characteristics, duration of use and
      clinical outcomes of older primary care patients prescribed benzodiazepines.
      METHODS: Computerized records were used to identify outpatients (n=129) aged
      >or=60 years who received new benzodiazepine prescriptions from primary care
      physicians of a group model managed care organization. A baseline telephone
      survey assessed indications for prescription, sleep quality (Pittsburgh Sleep
      Quality Index), depression (Symptom Checklist depression scale and Structured
      Clinical Interview for DSM-IV), alcohol use (CAGE) and functional status (SF-36).
      A 2-month follow-up survey assessed benzodiazepine use, sleep quality and
      depression. RESULTS: The most common indications for prescription were insomnia
      (42%) and anxiety (36%). At baseline, participants reported moderate sleep
      disturbance (mean Pittsburgh Sleep Quality Index=9.3, S.D.=4.0), only 15% met
      criteria for current depressive episode and only 3% reported at-risk alcohol use.
      After 2 months, 30% of participants used benzodiazepines at least daily. Both
      those continuing daily use and those not continuing daily use reported
      significant improvements in sleep quality and depression, with no difference
      between groups in rates of improvement. CONCLUSIONS: Initial benzodiazepine
      prescriptions to older adults are typically intended for the treatment of anxiety
      or insomnia, with little evidence for occult depression or alcohol abuse. A
      significant minority develops a pattern of long-term use, raising concerns about
      tolerance and dependence.

PMID- 16950373
TI  - Clinical differences among patients treated for mental health problems in general
      medical and specialty mental health settings in the National Comorbidity Survey
      Replication.
AB  - OBJECTIVE: General medical (GM) treatments for mental health disorders are less
      likely than specialty mental health (SMH) treatments to be adequate. We explored
      whether differences in the clinical characteristics of patients treated in each
      sector (GM-only or SMH-only) or in both sectors (GM+SMH) may help to explain this
      finding. METHOD: We analyzed data from the National Comorbidity Survey
      Replication (NCS-R), a nationally representative household survey of 5692 English
      speaking adult household residents that was carried out in 2001-2003. The NCS-R
      used a fully structured diagnostic interview to assess DSM-IV disorders,
      including mood, anxiety, impulse control and substance use disorders. We
      classified disorders in terms of a three-category severity gradient (serious,
      moderate and mild) based on information about clinically significant distress and
      role impairment. We collected self-report data on chronic physical conditions,
      sociodemographics and type of treatment received for emotional and substance use
      problems in the 12 months before the interview. RESULTS: Patients who received
      GM+SMH treatment had more severe mental disorders and a higher prevalence of mood
      and anxiety disorders than patients who received treatment in only one of the two
      sectors. Patients seen in the GM-only and GM+SMH sectors had more chronic
      physical conditions than patients seen in the SMH-only sector. CONCLUSION:
      Patient characteristics may partially explain the lower intensity and adequacy of
      GM treatment.

PMID- 16950374
TI  - Effect of depression on all-cause mortality in adults with cancer and
      differential effects by cancer site.
AB  - OBJECTIVE: The objective of this study was to compare the effect of depression on
      the risk of death in adults with and without cancer and by specific cancer site
      among those with cancer. RESEARCH DESIGN AND METHODS: We analyzed data on 10,025
      participants in the population-based National Health and Nutrition Examination
      Survey (NHANES) 1 Epidemiologic Follow-up Study. Four groups were created based
      on cancer and depression status in 1982: (a) no cancer, no depression (reference
      group; no CA, no DEP); (b) depression but no cancer (DEP, no CA); (c) cancer but
      no depression (CA, no DEP); and (d) cancer and depression (CA+DEP). Six CA sites
      were defined: lung, breast, gastrointestinal (GI), genitourinary (GU), skin and
      other. Cox proportional models were used to calculate adjusted hazard for death
      for each group compared with the reference group and by cancer site. RESULTS:
      Over 8 years (78,433 person-years of follow-up), 1925 deaths were documented. The
      mortality rate per 1000 person-years of follow-up was highest in the CA+DEP
      group. Compared to the reference group, the hazard ratios (HRs) for all-cause
      mortality were as follows: CA, no DEP: 1.43 [95% confidence interval (95%
      CI)=1.23-1.67]; DEP, no CA: 1.44 (95% CI=1.28-1.63); CA+DEP: 1.87 (95% CI=1.49
      2.34). HRs for depression by site were as follows: lung: 1.30 (95% CI=0.49-3.99);
      breast: 1.27 (95% CI=0.58-2.79); GI: 1.47 (95% CI=0.58-3.75); GU: 0.93 (95%
      CI=0.50-1.74); skin: 1.07 (95% CI=0.67-1.69); other: 2.13 (95% CI=0.55-8.25).
      CONCLUSION: The coexistence of cancer and depression is associated with a
      significantly increased risk of death, and the effect of depression on the risk
      of death differs by cancer site.

PMID- 16950375
TI  - Depressive symptoms following herpes simplex encephalitis--an underestimated
      phenomenon?
AB  - OBJECTIVE: In view of the herpes simplex virus' neurotropism for the limbic
      system and the temporal lobe, little is known about potential negative effects of
      this necrotizing encephalitis on affective functioning and health-related quality
      of life (HRQoL) after recovery. We therefore set out to explore an association
      between herpes simplex virus encephalitis (HSE) and both depressive symptoms and
      HRQoL. METHODS: A structured telephone interview was conducted in 26 subjects
      (F/M=10/16; age at follow-up, 49.3+/-15.0 years; range, 29-80) at a mean time
      interval of 5.2+/-3.1 years (range, 1-11) after their initial diagnosis of HSE.
      WHO-5 Well-Being Index (WHO-5) was used as screening instrument for depression,
      and Short Form-12 was used as HRQoL instrument. We also determined the spatial
      extent of morphologic abnormalities on magnetic resonance imaging (MRI). RESULTS:
      Ten of the interviewees (38.5%) had a WHO-5 score below 13, which is considered
      indicative of a depressive disorder. Accordingly, concerning their HRQoL,
      patients felt more impaired by affective than by physical symptoms. MRI ratings
      and WHO-5 score were not correlated. CONCLUSIONS: While this pilot study does not
      allow to establish a causal relationship with focal brain damage, findings
      suggest both a high frequency of depressive symptoms and a low quality of life
      with respect to mental health following HSE. These results should be confirmed by
      a prospective trial.

PMID- 16950377
TI  - Neuroticism and low educational level predict the risk of posttraumatic stress
      disorder in women after miscarriage or stillbirth.
AB  - OBJECTIVE: This study aimed to determine whether neuroticism and educational
      level predict posttraumatic stress disorder (PTSD) in women following an
      unsuccessful pregnancy. METHOD: Via advertisements, pregnant women with a
      gestational period shorter than 12 weeks were asked to participate in a study
      regarding their perception of pregnancy. After they had agreed, they were sent
      questionnaires, including a scale for neuroticism and their highest attained
      educational level. Every other month during the pregnancy and 1 month after the
      expected date of birth, they were sent brief questionnaires about the pregnancy.
      Participants for whom the pregnancy had ended unsuccessfully were contacted by
      phone and asked to participate in a follow-up study with a PTSD scale. RESULTS:
      Of the 1339 women studied, 126 (9%) experienced an unsuccessful pregnancy; 8 of
      these dropped out of the study (response rate, 94%); 1 had not indicated her
      educational level. The remaining 117 women filled out the PTSD scale after about
      1 month. Thirty-one women (26%) met the DSM-IV criteria for PTSD and 86 women did
      not. Logistic regression analysis revealed that PTSD was significantly associated
      with higher neuroticism, lower educational level and longer duration of
      gestation. CONCLUSION: For patients with a high educational level and low
      neuroticism score, the risk of developing PTSD was negligible, while for those
      with a low educational level and a high score for neuroticism, the estimated risk
      was about 70%. Care and guidance should focus primarily on the latter group.

PMID- 16950376
TI  - Is the association between posttraumatic stress disorder symptoms and poor health
      due to a common familial or genetic factor?
AB  - OBJECTIVE: The objective of this study was to identify genetic, familial and
      environmental contributions to the association between posttraumatic stress
      disorder (PTSD) symptoms and poor health. METHODS: A community sample of 1852
      twin pairs was assessed for symptoms of PTSD [with the Impact of Events Scale
      (IES)] and self-reported global health status using a single five-level question.
      An ordinal logistic regression model estimated odds ratio/s (OR) for the
      association between PTSD and health status. Within-pair analysis assessed
      confounding by familial and genetic factors and adjusted for the possible
      confounding influence of age, sex, race, education and self-reported physician
      diagnosis of depression. RESULTS: The IES was strongly and significantly
      associated with self-reported health [OR=1.8; 95% confidence interval (95%
      CI)=1.5-2.2; highest quartile vs. lowest quartile]. This association remained
      significant in within-pair analysis (OR=1.3; 95% CI=1.0-1.7), but after further
      adjustment for sociodemographics and depression, it was no longer significant
      (P(trend)=.17). Separate analysis by zygosity did not show differential effect in
      monozygotic or dizygotic pairs. CONCLUSION: These findings suggest that the
      association between PTSD symptoms and poor health is, in part, due to familial
      confounding and sociodemographic factors. Little evidence of confounding by
      genetic factors was found. These findings suggest that early prevention efforts
      would have the greatest potential for improving poor health in PTSD-prone
      patients, whereas later intervention efforts directed at treating PTSD may have a
      more limited impact on improving poor health.

PMID- 16950378
TI  - The role of oxidative stress in postoperative delirium.
AB  - AIM: This study aimed to determine a marker that predicts delirium using
      preoperative oxidative processes in patients undergoing cardiopulmonary bypass
      surgery. METHOD: Twelve of the 50 patients included in the study showed signs of
      delirium during postoperative follow-up. The Delirium Rating Scale was used in
      patients with delirium according to DSM-IV-TR in the postoperative period. Venous
      blood samples were obtained from the patients the day before and the day after
      the surgery to determine plasma antioxidant enzyme levels. RESULTS: While there
      were no differences in preoperative superoxide dismutase (SOD), glutathione
      peroxidase (GSH-Px) and malondialdehyde (MDA) levels in both groups, catalase
      (CAT) levels were significantly lower in the delirium group. Postoperative SOD
      and MDA levels were also higher in the delirium group, while the GSH-Px levels
      were found to be lower when compared with those during the preoperative period.
      In the nondelirium group, the postoperative MDA and GSH-Px levels were found to
      be lower than preoperative levels, and postoperative SOD levels were found to be
      higher than preoperative levels. CAT levels were lower in the delirium group when
      the pre- and postoperative levels were compared in both groups. The postoperative
      levels of SOD, GSH-Px and CAT in the nondelirium group and MDA in the delirium
      group were significantly higher than preoperative levels. CONCLUSION: Patients
      with low preoperative CAT levels appeared to be more susceptible to delirium than
      patients with higher CAT levels.

PMID- 16950379
TI  - Determinants of psychiatric hospitalization after attempted suicide.
AB  - OBJECTIVE: This study investigated the characteristics of suicide attempters
      referred to psychiatric hospitals and the factors affecting such referral.
      METHOD: All 1198 consecutive suicide attempters treated in general hospital
      emergency rooms in Helsinki during a 12-month period were identified. Data on all
      health care contacts 1 year before the index attempt and on referrals to
      psychiatric hospitals after the attempt were gathered. RESULTS: We found that a
      quarter of patients were referred to psychiatric hospitals as inpatients after
      index suicide attempts. Factors predicting referral to psychiatric hospitals,
      compared to nonreferral, were older age, psychotic disorder, mood disorder, lack
      of alcohol consumption preceding the attempt, somatic illness, suicide attempt on
      a weekday, previous psychiatric treatment, psychiatric consultation and the
      hospital treating the suicide attempt. CONCLUSION: Although the clinical
      characteristics of patients attempting suicide are a major determinant of whether
      they are subsequently referred to psychiatric hospitals, the treatment practices
      of emergency room hospitals also influence treatment decisions.

PMID- 16950380
TI  - Heisenberg in the ER: observation appears to reduce involuntary intramuscular
      injections in a psychiatric emergency service.
AB  - INTRODUCTION: Chemical restraint is controversial. Appropriate use is ill-defined
      and chemical restraint may be overutilized. During the period of an unrelated
      observational study for patients with acute psychomotor agitation in a
      psychiatric emergency service, we noticed a significant reduction in the number
      of involuntary intramuscular injections administered. RESULTS: We observed a 27%
      decrease (P=.015) in the number of involuntary intramuscular injections in the 3
      month observational study period, compared to 3-month periods before and after
      the study. CONCLUSION: We suggest that the observation process itself may have
      been beneficial and may have reduced the incidence of unnecessary intramuscular
      injections.

PMID- 16950381
TI  - Factors influencing the stability of psychiatric diagnoses in the emergency
      setting: review of 934 consecutively inpatient admissions.
AB  - OBJECTIVE: This study aimed to examine the stability of psychiatric emergency
      diagnoses and factors influencing diagnostic concordance. METHODS: The
      concordance between psychiatric emergency and inpatient diagnoses was calculated
      using kappa coefficient. The groups with and without psychiatric diagnostic
      stability were compared to determine factors influencing diagnostic stability.
      RESULTS: Agreement between psychiatric emergency and inpatient diagnoses was fair
      (range of kappa=.48-.56) for bipolar, schizophrenia, schizoaffective and
      depressive disorders. Results indicated that patients with stable diagnoses
      between psychiatric emergency and inpatient settings are likely to arrive on
      legal holds and that patients without concurring diagnoses are likely to have a
      higher medical burden. CONCLUSION: Further studies exploring ways to improve
      diagnostic stability in psychiatric emergency setting are warranted.

PMID- 16950382
TI  - A survey of psychiatric liaison services for older adults in the eastern region
      of the United Kingdom.
AB  - AIMS AND METHODS: The aim of this study was to investigate the provision of
      liaison services for older adults in the Eastern Region of the UK. We surveyed
      all the acute general hospitals for current service and problems encountered in
      delivering and developing these services. RESULTS: The survey had a 100%
      response. Sixty-two percent did not have a dedicated liaison service. The
      predominant model of service delivery was nurse led. The majority of the services
      had evolved over the last 2 years and had time limited funding only. In two
      hospitals the service had ceased due to lack of continuing funding. CLINICAL
      IMPLICATIONS: The survey has highlighted liaison services for older people and
      show that they remain a neglected area. This survey provides information that
      will be useful to commissioners and providers who are developing liaison
      psychiatry services for older people.

PMID- 16950383
TI  - Electroconvulsive therapy complicated by life-threatening hyperkalemia in a
      catatonic patient.
AB  - Electroconvulsive therapy (ECT) requires brief general anesthesia, and
      succinylcholine is a depolarizing neuromuscular blocking agent that is frequently
      used for this procedure. Its use leads to intracellular potassium release into
      the extracellular space, usually increasing the serum potassium level by 0.5-1
      mEq/L, with little clinical significance. However, long-term immobilization has
      been associated with changes at the neuromuscular junction (up-regulation of
      nicotinic cholinergic receptors) and subsequent serious hyperkalemia following
      succinylcholine administration. We report the case of a severely obese patient,
      immobilized due to her catatonic state, who developed life-threatening
      ventricular tachycardia after succinylcholine administration for ECT. Resumption
      of normal physical activity reverses these neuromuscular junctional changes,
      allowing subsequent safe succinylcholine administration. Current drug development
      may eliminate the need for succinylcholine use during ECT.

PMID- 16950384
TI  - Posttraumatic Kleine-Levin syndrome.

PMID- 16950385
TI  - Case report: recognizing first onset of rumination disorder in adults.

PMID- 16950386
TI  - Multiple sclerosis presenting with fantastic confabulation.
AB  - Multiple sclerosis (MS) is the most common inflammatory, demyelinating disease of
      the central nervous system. Besides neurological signs and symptoms, the disease
      may be associated with various psychiatric manifestations, and uncommonly,
      psychiatric manifestations may be the presenting symptom. On the other hand,
      confabulation is defined as falsification of memory occurring in clear
      consciousness in association with an organically derived amnesia or as
      spontaneous narrative reports of events that never happened. We report an unusual
      association of confabulation with MS. A 23-year-old man was admitted to a
      hospital, telling unusual stories. After evaluation and a detailed workup, the
      patient was given the diagnosis of MS with fantastic confabulations.
      Neuropsychological evaluation revealed mild frontal lobe dysfunction.
      Confabulation has been reported after frontal lobe lesions and is also
      hypothesized to be associated with a deficit primarily in the retrieval of more
      than one of the following: encoding, consolidation or storage. Clinicians'
      awareness of this kind of rare association may further enlighten the neural basis
      of confabulation.

PMID- 16950387
TI  - Depressive disorder with psychotic symptoms as psychiatric presentation of
      sporadic Creutzfeldt-Jakob disease: a case report.
AB  - Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disease and shows a
      wide range of early clinical manifestation. We report the case of Ms. A, a 50
      year-old woman, who exhibited an atypical psychiatric presentation of CJD at the
      beginning of the disease, as a depressive disorder with psychotic features. We
      discuss this case, the clinical attitudes that can lead to misdiagnose such
      presentation of CJD with other psychiatric diseases, and propose to repeat
      complementary investigations when the diagnostic is evocated, even if these tests
      are often negative or nonspecific in the early stages of CJD.

PMID- 16950388
TI  - Three patients with hemophagocytic syndrome who developed acute organic brain
      syndrome.
AB  - INTRODUCTION: We describe three patients with hemophagocytic syndrome (HPS) who
      developed acute organic brain syndrome. All three presented with high-grade fever
      and twilight state, and were admitted to our hospital. After admission, delirium
      developed in all three. As delirium improved, various other psychiatric symptoms,
      including hallucinations, agitation, hypoactivity, affective lability and
      insomnia, were noted. DISCUSSION: When treated with steroid hormones,
      immunoglobulin and neuroleptics, all patients demonstrated improvement in their
      psychiatric symptoms, as well as in their general condition and laboratory
      findings. Ultimately, they all recovered and were discharged. CONCLUSION: It
      needs to be noted that organic brain syndrome might be observed at the onset of
      HPS. Consequently, early diagnosis and treatment for psychiatric symptoms, as
      well as for HPS, are crucial.

PMID- 16950389
TI  - Reversible cerebral atrophy: a case report and literature review.

PMID- 16950390
TI  - Archaeal N-terminal protein maturation commonly involves N-terminal acetylation:
      a large-scale proteomics survey.
AB  - We present the first large-scale survey of N-terminal protein maturation in
      archaea based on 873 proteomically identified N-terminal peptides from the two
      haloarchaea Halobacterium salinarum and Natronomonas pharaonis. The observed
      protein maturation pattern can be attributed to the combined action of methionine
      aminopeptidase and N-terminal acetyltransferase and applies to cytosolic proteins
      as well as to a large fraction of integral membrane proteins. Both N-terminal
      maturation processes primarily depend on the amino acid in penultimate position,
      in which serine and threonine residues are over represented. Removal of the
      initiator methionine occurs in two-thirds of the haloarchaeal proteins and
      requires a small penultimate residue, indicating that methionine aminopeptidase
      specificity is conserved across all domains of life. While N-terminal acetylation
      is rare in bacteria, our proteomic data show that acetylated N termini are common
      in archaea affecting about 15% of the proteins and revealing a distinct archaeal
      N-terminal acetylation pattern. Haloarchaeal N-terminal acetyltransferase reveals
      narrow substrate specificity, which is limited to cleaved N termini starting with
      serine or alanine residues. A comparative analysis of 140 ortholog pairs with
      identified N-terminal peptide showed that acetylatable N-terminal residues are
      predominantly conserved amongst the two haloarchaea. Only few exceptions from the
      general N-terminal acetylation pattern were observed, which probably represent
      protein-specific modifications as they were confirmed by ortholog comparison.

PMID- 16950391
TI  - Direct evidence for a glutamate switch necessary for substrate recognition:
      crystal structures of lysine epsilon-aminotransferase (Rv3290c) from
      Mycobacterium tuberculosis H37Rv.
AB  - Lysine epsilon-aminotransferase (LAT) is a PLP-dependent enzyme that is highly up
      regulated in nutrient-starved tuberculosis models. It catalyzes an overall
      reaction involving the transfer of the epsilon-amino group of L-lysine to alpha
      ketoglutarate to yield L-glutamate and alpha-aminoadipate-delta-semialdehyde. We
      have cloned and characterized the enzyme from Mycobacterium tuberculosisH37Rv. We
      report here the crystal structures of the enzyme, the first from any source, in
      the unliganded form, external aldimine with L-lysine, with bound PMP and with its
      C5 substrate alpha-ketoglutarate. In addition to interaction details in the
      active site, the structures reveal a Glu243 "switch" through which the enzyme
      changes substrate specificities. The unique substrate L-lysine is recognized
      specifically when Glu243 maintains a salt-bridge with Arg422. On the other hand,
      the binding of the common C5 substrates L-glutamate and alpha-ketoglutarate is
      enabled when Glu243 switches away and unshields Arg422. The structures reported
      here, sequence conservation and earlier mutational studies suggest that the
      "glutamate switch" is an elegant solution devised by a subgroup of fold type I
      aminotransferases for recognition of structurally diverse substrates in the same
      binding site and provides for reaction specificity.

PMID- 16950392
TI  - The 15 SCR flexible extracellular domains of human complement receptor type 2 can
      mediate multiple ligand and antigen interactions.
AB  - Complement receptor type 2 (CR2, CD21) is a cell surface protein that links the
      innate and adaptive immune response during the activation of B cells. The
      extracellular portion of CR2 comprises 15 or 16 short complement regulator (SCR)
      domains, for which the overall arrangement in solution is unknown. This was
      determined by constrained scattering and ultracentrifugation modelling. The
      radius of gyration of CR2 SCR 1-15 was determined to be 11.5 nm by both X-ray and
      neutron scattering, and that of its cross-section was 1.8 nm. The distance
      distribution function P(r) showed that the overall length of CR2 SCR 1-15 was 38
      nm. Sedimentation equilibrium curve fits gave a mean molecular weight of 135,000
      (+/- 13,000) Da, in agreement with a fully glycosylated structure. Velocity
      experiments using the g*(s) derivative method gave a sedimentation coefficient of
      4.2 (+/- 0.1) S. In order to construct a model of CR2 SCR 1-15 for constrained
      fitting, homology models for the 15 SCR domains were combined with randomised
      linker peptides generated by molecular dynamics simulations. Using an automated
      procedure, the analysis of 15,000 possible CR2 SCR 1-15 models showed that only
      those models in which the 15 SCR domains were flexible but partially folded back
      accounted for the scattering and sedimentation data. The best-fit CR2 models
      provided a visual explanation for the versatile interaction of CR2 with four
      ligands C3d, CD23, gp350 and IFN-alpha. The flexible location of CR2 SCR 1-2 is
      likely to facilitate interactions of C3d-antigen complexes with the B cell
      receptor.

PMID- 16950393
TI  - The energetic network of hotspot residues between Cdc25B phosphatase and its
      protein substrate.
AB  - We have investigated the functional network of hotspot residues at the remote
      docking site of two cell cycle regulators, namely Cdc25B phosphatase and its
      native protein substrate Cdk2-pTpY/CycA. Specifically, we have studied the roles
      of energetically important residues (Arg488, Arg492, Tyr497 on Cdc25B and Asp206
      and Asp210 on Cdk2-pTpY/CycA) by generating a diverse set of substitutions and
      performing double and triple mutant cycle analyses. This transient protein
      protein interaction is particularly well-suited for this mutagenic approach
      because various control experiments ensure that the effect of each mutation is
      limited to the interaction of interest. We find binary coupling energies for ion
      pairs and hydrogen bonds ranging from 0.7 kcal/mol to 3.9 kcal/mol and ternary
      coupling energies of 1.9 kcal/mol and 2.8 kcal/mol. Overall our biochemical
      analyses are in good agreement with the docked structure of the complex and
      suggest the following roles for the individual hotspot residues on Cdc25B. The
      most important contributor, Arg492, forms a specific and tight bidentate
      interaction with Asp206 and a weaker interaction with Asp210 that cannot be
      replaced by a Lys. Although Tyr497 does not directly participate in this ionic
      network, it is important for buttressing Arg492 using both its hydrophobic
      (aromatic ring) and hydrophilic characteristics (hydrogen bonding). Arg488
      participates less specifically in the electrostatic network with Asp206 and
      Asp210 of the protein substrate as it can partially be replaced by Lys. Our data
      provide insight how a cluster of residues in a docking site remote from the site
      of the chemical reaction can bring about efficient and specific substrate
      recognition.

PMID- 16950394
TI  - Crystal structures of human tissue kallikrein 4: activity modulation by a
      specific zinc binding site.
AB  - Human tissue kallikrein 4 (hK4) belongs to a 15-member family of closely related
      serine proteinases. hK4 is predominantly expressed in prostate, activates
      hK3/PSA, and is up-regulated in prostate and ovarian cancer. We have identified
      active monomers of recombinant hK4 besides inactive oligomers in solution. hK4
      crystallised in the presence of zinc, nickel, and cobalt ions in three crystal
      forms containing cyclic tetramers and octamers. These structures display a novel
      metal site between His25 and Glu77 that links the 70-80 loop with the N-terminal
      segment. Micromolar zinc as present in prostatic fluid inhibits the enzymatic
      activity of hK4 against fluorogenic substrates. In our measurements, wild-type
      hK4 exhibited a zinc inhibition constant (IC50) of 16 microM including a
      permanent residual activity, in contrast to the zinc-independent mutants H25A and
      E77A. Since the Ile16 N terminus of wild-type hK4 becomes more accessible for
      acetylating agents in the presence of zinc, we propose that zinc affects the hK4
      active site via the salt-bridge formed between the N terminus and Asp194 required
      for a functional active site. hK4 possesses an unusual 99-loop that creates a
      groove-like acidic S2 subsite. These findings explain the observed specificity of
      hK4 for the P1 to P4 substrate residues. Moreover, hK4 shows a negatively charged
      surface patch, which may represent an exosite for prime-side substrate
      recognition.

PMID- 16950395
TI  - hCLE/CGI-99, a human protein that interacts with the influenza virus polymerase,
      is a mRNA transcription modulator.
AB  - The human protein hCLE was previously identified by its interaction with the PA
      subunit of influenza virus polymerase. It exhibits a sequence similarity of 38%
      with the yeast Spt16 component of the FACT complex, which is involved in
      transcriptional regulation. Therefore, we studied the possible relationship of
      hCLE with the transcription machinery. Here we show that hCLE and different
      phosphorylated forms of the RNA polymerase II (RNAP II) largest subunit, co
      immunoprecipitate and colocalize by confocal microscopy analysis. Furthermore,
      hCLE was found in nuclear sites of active mRNA synthesis, as demonstrated by its
      colocalization with spots of in situ Br-UTP incorporation. Silencing of hCLE
      expression by RNA interference inhibited the synthesis of RNAP II transcripts
      around 50%. Accordingly, the expression profiling in hCLE-silenced cells studied
      by microarray analysis showed that, among the genes that exhibited a differential
      expression under hCLE silencing, more than 90% were down-regulated. Collectively
      these results indicate that hCLE works as a positive modulator of the RNA
      polymerase II activity.

PMID- 16950396
TI  - Quantitative evaluation of each catalytic subsite of cathepsin B for inhibitory
      activity based on inhibitory activity-binding mode relationship of epoxysuccinyl
      inhibitors by X-ray crystal structure analyses of complexes.
AB  - To quantitatively estimate the inhibitory effect of each substrate-binding
      subsite of cathepsin B (CB), a series of epoxysuccinyl derivatives with different
      functional groups bound to both carbon atoms of the epoxy ring were synthesized,
      and the relationship between their inhibitory activities and binding modes at CB
      subsites was evaluated by the X-ray crystal structure analyses of eight
      complexes. With the common reaction in which the epoxy ring of inhibitor was
      opened to form a covalent bond with the SgammaH group of the active center Cys29,
      the observed binding modes of the substituents of inhibitors at the binding
      subsites of CB enabled the quantitative assessment of the inhibitory effect of
      each subsite. Although the single blockage of S1' or S2' subsite exerts only the
      inhibitory effect of IC50 = approximately 24 microM (k2 = approximately 1250 M(
      1) s(-1)) or approximately 15 microM (k2 = approximately 1800 M(-1) s(-1)),
      respectively, the synchronous block of both subsites leads to IC50 =
      approximately 23 nM (k2 = 153,000 - 185,000 M(-1) s(-1)), under the condition
      that (i) the inhibitor possesses a P1' hydrophobic residue such as Ile and a P2'
      hydrophobic residue such as Ala, Ile or Pro, and (ii) the C-terminal carboxyl
      group of a P2' residue is able to form paired hydrogen bonds with the imidazole
      NH of His110 and the imidazole N of His111 of CB. The inhibitor of a Pn' > or =
      3' substituent was not potentiated by collision with the occluding loop. On the
      other hand, it was suggested that the inhibitory effects of Sn subsites are
      independent of those of Sn' subsites, and the simultaneous blockage of the funnel
      like arrangement of S2 and S3 subsites leads to the inhibition of IC50 =
      approximately 40 nM (k2 = approximately 66,600 M(-1) s(-1)) regardless of the
      lack of Pn' substituents. Here we present a systematic X-ray structure-based
      evaluation of structure-inhibitory activity relationship of each binding subsite
      of CB, and the results provide the structural basis for designing a more potent
      CB-specific inhibitor.

PMID- 16950397
TI  - Cofacial heme binding is linked to dimerization by a bacterial heme transport
      protein.
AB  - Campylobacter jejuni is a leading bacterial cause of food-borne illness in the
      developed world. Like most pathogens, C. jejuni requires iron that must be
      acquired from the host environment. Although the iron preference of the food
      borne pathogen C. jejuni is not established, this organism possesses heme
      transport systems to acquire iron. ChaN is an iron-regulated lipoprotein from C.
      jejuni proposed to be associated with ChaR, an outer-membrane receptor. Mutation
      of PhuW, a ChaN orthologue in Pseudomonas aeruginosa, compromises growth on heme
      as a sole iron source. The crystal structure of ChaN, determined to 1.9 A
      resolution reveals that ChaN is comprised of a large parallel beta-sheet with
      flanking alpha-helices and a smaller domain consisting of alpha-helices.
      Unexpectedly, two cofacial heme groups ( approximately 3.5 A apart with an inter
      iron distance of 4.4 A) bind in a pocket formed by a dimer of ChaN monomers. Each
      heme iron is coordinated by a single tyrosine from one monomer, and the
      propionate groups are hydrogen bonded by a histidine and a lysine from the other
      monomer. Sequence analyses reveal that these residues are conserved among ChaN
      homologues from diverse bacterial origins. Electronic absorption and electron
      paramagnetic resonance (EPR) spectroscopy are consistent with heme binding
      through tyrosine coordination by ChaN in solution yielding a high-spin heme iron
      structure in a pH-dependent equilibrium with a low-spin species. Analytical
      ultracentrifugation demonstrates that apo-ChaN is predominantly monomeric and
      that dimerization occurs with heme binding such that the stability constant for
      dimer formation increases by 60-fold.

PMID- 16950398
TI  - Structure of the SCAN domain from the tumor suppressor protein MZF1.
AB  - The SCAN domain mediates interactions between members of a subfamily of zinc
      finger transcription factors and is found in more than 60 C2H2 zinc finger genes
      in the human genome, including the tumor suppressor gene myeloid zinc finger 1
      (MZF1). Glutathione-S-transferase pull-down assays showed that the MZF1 SCAN
      domain self-associates, and a Kd value of 600 nM was measured by intrinsic
      tryptophan fluorescence polarization. The MZF1 structure determined by NMR
      spectroscopy revealed a domain-swapped dimer. Each monomer consists of five alpha
      helices in two subdomains connected by the alpha2-alpha3 loop. Residues from
      helix 3 of each monomer compose the core of the dimer interface, while the alpha1
      alpha2 loop and helix 2 pack against helices 3 and 5 from the opposing monomer.
      Comprehensive sequence analysis is coupled with the first high-resolution
      structure of a SCAN dimer to provide an initial view of the recognition elements
      that govern dimerization for this large family of transcription factors.

PMID- 16950399
TI  - High resolution structure of BipD: an invasion protein associated with the type
      III secretion system of Burkholderia pseudomallei.
AB  - Burkoldheria pseudomallei is a Gram-negative bacterium that possesses a protein
      secretion system similar to those found in Salmonella and Shigella. Recent work
      has indicated that the protein encoded by the BipD gene of B. pseudomallei is an
      important secreted virulence factor. BipD is similar in sequence to IpaD from
      Shigella and SipD from Salmonella and is therefore likely to be a translocator
      protein in the type-III secretion system of B. pseudomallei. The crystal
      structure of BipD has been solved at a resolution of 2.1 A revealing the detailed
      tertiary fold of the molecule. The overall structure is appreciably extended and
      consists of a bundle of antiparallel alpha-helical segments with two small beta
      sheet regions. The longest helices of the molecule form a four-helix bundle and
      most of the remaining secondary structure elements (three helices and two three
      stranded beta-sheets) are formed by the region linking the last two helices of
      the four-helix bundle. The structure suggests that the biologically active form
      of the molecule may be a dimer formed by contacts involving the C-terminal alpha
      helix, which is the most strongly conserved part of the protein. Comparison of
      the structure of BipD with immunological and other data for IpaD indicates that
      the C-terminal alpha-helix is also involved in contacts with other proteins that
      form the translocon.

PMID- 16950400
TI  - Cingulate gyrus volumetry in drug free bipolar patients and patients treated with
      valproate or valproate and quetiapine.
AB  - In patients with bipolar disorder, recent brain imaging studies have reported
      cingulate cortex volume change. We performed a volumetric magnetic resonance
      imaging (MRI) study to assess the subregions of the cingulate gyrus; left
      anterior cingulate (LAC), left posterior cingulate (LPC), right anterior
      cingulate (RAC), and right posterior cingulate (RPC). Our sample consisted of
      bipolar patients that are either unmedicated (n=10), on valproate monotherapy
      (n=10) or on valproate plus quetiapine (n=10) versus healthy comparisons (n=10).
      Thirty right-handed bipolar disordered patients were recruited. Of them, 10 were
      first-applying patients who never had taken any drug for this condition
      (medication-naive group), 10 were on valproate treatment (valproate group) and 10
      were on valproate plus quetiapine treatment (valproate plus quetiapine group).
      Cingulate gyrus volumes included both cortex and white matter. Drug-free patients
      had significantly smaller LAC and LPC volumes compared with valproate and
      valproate plus quetiapine groups and healthy controls. In addition, in post hoc
      comparisons, a trend toward significant difference was found between valproate
      plus quetiapine group and valproate group in regard to only LAC. Our findings
      suggest that valproate and quetiapine may have neuroprotective effects.

PMID- 16950401
TI  - Solving the puzzle of schizophrenia: Piece by piece.

PMID- 16950402
TI  - PepT1 mediates colon damage by transporting fMLP in rats with bowel resection.
AB  - BACKGROUND: The intestinal oligopeptide transporter (PepT1) is responsible for
      the absorption of nutrient di-tripeptide and mediates the transportation of
      bacterial product N-formylmethionylleucyl-phenylalanine (fMLP) that induces
      intestinal inflammation. PepT1 is absent from normal colon epithelia but is
      abnormally expressed in the colon of patients with inflammatory bowel diseases.
      This study was designed to investigate the role of PepT1 in colonic inflammation
      and its relation with fMLP. MATERIALS AND METHODS: PepT1 mRNA expression was
      analyzed by RT-PCR and oligopeptide transportation was quantified by the luminal
      perfusion with cephalexin in rats following 80% small bowel resection. The
      inflammatory effects of PepT1-mediated fMLP transport were also investigated by
      the measurement of myeloperoxidase (MPO) activity, histological analysis, and the
      use of Gly-Gly (Glycine-Glycine, a competitive PepT1 blocker). RESULTS: The
      overexpression of PepT1 was observed, peaking at 2 weeks post-operation, with its
      levels declining to 12% at week 4. The ability of oligopeptide transport was
      correlated with the PepT1 levels. The fMLP perfusion into the colon of rats with
      bowel resection resulted in an increased MPO activity and mucosal inflammation at
      week 2, but not at week 4 post-operation. The administration of Gly-Gly (50 mm)
      competitively inhibited PepT1, reducing the fMLP-associated MPO activation and
      colonic mucosal damage. CONCLUSIONS: The colonic PepT1 overexpression induced by
      bowel resection increases the transport of bacterial product fMLP and hence
      causes colonic inflammation, which may serve as a previously unrecognized pathway
      resulting in colon mucosa damage.

PMID- 16950403
TI  - Involvement of c-Met/hepatocyte growth factor pathway in cholangiocarcinoma cell
      invasion and its therapeutic inhibition with small interfering RNA specific for c
      Met.
AB  - BACKGROUND: Hepatocyte growth factor receptor (c-Met) plays an important role in
      many functions of cancer cells. We examined the roles of c-Met and its downstream
      signaling molecules in cholangiocarcinoma cell lines RMCCA1 and HuCCA1. MATERIALS
      AND METHODS: The expression of c-Met and their signaling cascades were determined
      in RMCCA1 and HuCCA1 cholangiocarcinoma cell lines by Western blotting. Small
      interfering RNA (siRNA) specific for c-Met was used to suppress the expression of
      c-Met. The proliferation, migration and invasion assay were tested in these
      cholangiocarcinoma cells treated with hepatocyte growth factor (HGF). RESULTS:
      Activation of c-Met with HGF triggered the signaling via the ERK cascade mediated
      by sequential phosphorylation of MEK1/2 and MAPK and induction of
      cholangiocarcinoma cell invasion. The expression of c-Met in cholangiocarcinoma
      cells was suppressed by treatment with small interfering RNA (siRNA) specific for
      c-Met, and resulted in decrease in phosphorylation of MEK1/2. Furthermore,
      treatment with siRNA specific for c-Met or MEK inhibitor U0126 inhibited
      cholangiocarcinoma cell invasion induced by HGF. CONCLUSIONS: These results
      indicated that HGF and c-Met involved in the mechanism of cholangiocarcinoma cell
      invasion. It implies a potential role for the inhibition of c-Met in the
      treatment of cholangiocarcinoma.

PMID- 16950404
TI  - Population biology of multispecies helminth infection: competition and
      coexistence.
AB  - The role that interspecific interactions play in shaping parasite communities is
      uncertain. To date, models of competition between helminth species have assumed
      that interaction occurs through parasite-induced host death. To our knowledge,
      there has been no theoretical exploration of other forms of competition. We
      examine models in which competition acts at the point of establishment within the
      host, and at the time of egg production by the adult worm. The models used are
      stochastic and we allow hosts to vary in their rate of exposure to infective
      larvae. We derive the Lotka-Volterra model of competition when exposure is
      homogenous and thus demonstrate that two helminth species cannot coexist on a
      single limiting resource. We show that coexistence of species is promoted by
      heterogeneity in host exposure provided that the rates of exposure to the two
      species are not perfectly correlated, and, if they are positively correlated,
      provided that the degree of heterogeneity in host exposure is similar for the two
      competing helminth species. These results are robust to the mechanism of
      competition.

PMID- 16950405
TI  - Optimal conservation strategy in fluctuating environments with species
      interactions: resource-enhancement of the native species versus extermination of
      the alien species.
AB  - Alien species are often a major threat to native species. We consider optimal
      conservation strategies for a population whose viability is affected both by an
      alien species (such as a competitor, a predator, or a pathogen) and by random
      fluctuations of the environment (e.g. precipitation, temperature). We assume that
      the survivorship of the native population can be improved by providing resources
      such as food and shelter, and also by an extermination effort that decreases the
      abundance of the alien species. These efforts decrease the extinction probability
      of the native population, but they are accompanied by economic costs. We search
      for the optimal strategy that minimizes the weighted sum of the extinction
      probability and the economic costs over a single year. We derive conditions under
      which investment should be made in both resource-enhancement and extermination,
      and examine how the optimal effort levels change with parameters. When the
      optimal strategy includes both types of efforts, the optimal extermination effort
      level turns out to be independent of the density and economic value of the native
      species, or the variance of the environmental fluctuation. Furthermore, the
      optimal resource-enhancement effort is then independent of the density of the
      alien species. However, the parameter dependencies greatly change if one of the
      efforts becomes zero. We also examine the situation in which the impact of the
      alien species is uncertain. The optimal extermination effort increases with the
      uncertainty of this impact except when the cost of extermination is very high.

PMID- 16950406
TI  - Lipophilicity of capsaicinoids and capsinoids influences the multiple activation
      process of rat TRPV1.
AB  - Analogs of capsaicin, such as capsaicinoids and capsinoids, activate a cation
      channel, transient receptor potential cation channel vanilloid subfamily 1
      (TRPV1), and then increase the intracellular calcium concentration ([Ca2+]i).
      These compounds would be expected to activate TRPV1 via different mechanism(s),
      depending on their properties. We synthesized several capsaicinoids and
      capsinoids that have variable lengths of acyl moiety. The activities of these
      compounds towards TRPV1 heterologously expressed in HEK293 cells were determined
      by measuring [Ca2+]i. When an extracellular or intracellular Ca2+ source was
      removed, some agonists such as capsaicin could increase [Ca2+]i. However, a
      highly lipophilic capsaicinoid containing C18:0 and capsinoids containing C14:0,
      C18:0, or C18:1 (the latter was named olvanilate) could not elicit a large
      increase in [Ca2+]i in the absence of an extracellular or intracellular Ca2+
      source. These results suggest that highly lipophilic compounds cause only a
      slight Ca2+ influx, via TRPV1 in the plasma membrane, and are not able to
      activate TRPV1 in the endoplasmic reticulum.

PMID- 16950407
TI  - Cytochrome P450 1A isoenzymes in brain cells: Expression and inducibility in
      cultured rat brain neuronal and glial cells.
AB  - Studies initiated to determine the expression of CYP1A1/1A2 isoenzymes in the
      primary cultures of rat brain neuronal and glial cells revealed significant
      activity of CYP1A-dependent 7-ethoxyresorufin-o-dealkylase (EROD) in microsomes
      prepared from both rat brain neuronal and glial cells. RT-PCR and
      immunocytochemical studies demonstrated constitutive mRNA and protein expression
      of CYP1A1 and 1A2 isoenzymes in cultured neuronal and glial cells. Cultured
      neurons exhibited relatively higher constitutive mRNA and protein expression of
      CYP1A1 and 1A2 isoenzymes, associated with higher activity of EROD than the glial
      cells. Induction studies with 3-methylchlorantherene (MC), a known CYP1A-inducer,
      resulted in significant concentration dependent increase in the activity of EROD
      in cultured rat brain cells with glial cells exhibiting a greater magnitude of
      induction than the neuronal cells. This difference in the increase in enzyme
      activity was also observed with RT-PCR and immunocytochemical studies, indicating
      relatively higher increase in CYP1A1 and 1A2 mRNA as well as protein expression
      in the cultured glial cells when compared to the neuronal cells. The greater
      magnitude of induction of CYP1A1 in glial cells is of significance, as these
      cells are components of the blood-brain barrier and it is suggested that they
      have a potential role in the toxication-detoxication mechanism. Our data
      indicating differences in the expression and sensitivity of CYP1A1 isoenzymes in
      cultured rat brain cells will not only help in identifying and distinguishing
      xenobiotic metabolizing capability of these cells but also in understanding the
      vulnerability of these specific cell types towards neurotoxicants.

PMID- 16950408
TI  - Fructose-induced peroxynitrite production is mediated by methylglyoxal in
      vascular smooth muscle cells.
AB  - Methylglyoxal (MG), a highly reactive molecule, has been implicated in the
      development of insulin resistance. We investigated whether fructose, a precursor
      of MG, induced ONOO(-) generation and whether this process was mediated via
      endogenously increased MG formation. Fructose significantly increased MG
      generation in vascular smooth muscle cells (VSMCs) in a concentration and time
      dependent manner. The intracellular production of MG was increased by 153+/-23%
      or 259+/-28% after cells were treated 6 h with fructose (15 mM or 30 mM),
      compared with production from untreated cells (p<0.01, n=4 for each group). A
      significant increase in the production of ONOO(-), NO, and O(2)(*-), was found in
      the cells treated with fructose (15 mM) or MG (10 microM). Fructose- or MG
      induced ONOO(-) generation was significantly inhibited by MG scavengers,
      including reduced glutathione or N-acetyl-l-cysteine, and by O(2)(*-) or NO
      inhibitors, such as diphenylene iodonium, superoxide dismutase or N-nitro-l
      arginine methyl ester. Moreover, an enhanced iNOS expression was also observed in
      the cells treated directly with MG which was significantly inhibited when co
      application with N-acetyl-l-cysteine. Our results demonstrated that fructose is
      capable of inducing a significant increase in ONOO(-) production, which is
      mediated by an enhanced formation of endogenous MG in VSMCs.

PMID- 16950409
TI  - Role of Ras in ethanol modulation of angiotensin II activated p42/p44 MAP kinase
      in rat hepatocytes.
AB  - Angiotensin II plays a role in both liver cell proliferation and liver injury but
      the effects of ethanol on angiotensin II signaling in liver are not clearly
      understood. We have investigated the role of Ras in ethanol modulation of p42/p44
      mitogen-activated protein kinase (MAPK) stimulated by angiotensin II (Ang II) in
      primary cultures of rat hepatocytes. Hepatocytes were incubated with ethanol (100
      mM) for 24 h, then stimulated with Ang II (100 nM). The level of p42/p44 MAPK
      phosphorylation was measured by Western blot analysis and Ras activation was
      assessed by specific binding of Ras-GTP (activated form) to a GST-RBD fusion
      protein containing Ras-binding domain (RBD) of Raf-1. Ethanol potentiated p42/p44
      MAPK activation by Ang II, whereas ethanol alone did not significantly affect
      phosphorylation of p42/p44 MAPK. Ang II increased Ras activity by about 2 fold.
      Ethanol exposure increased Ang II stimulated Ras activity by an additional about
      2 fold. Ethanol alone elicited a small increase in basal Ras activity.
      Pretreatment with manumycin A (10 microM), a Ras farnesylation inhibitor,
      partially blocked both Ang II-activated and ethanol-potentiated MAPK activities.
      These data provided the first evidence that ethanol potentiation of Ang II
      stimulated p42/p44 MAPK is mediated, in part, by Ras in hepatocytes.

PMID- 16950410
TI  - Analgesic action of nicotine on tibial nerve transection (TNT)-induced mechanical
      allodynia through enhancement of the glycinergic inhibitory system in spinal
      cord.
AB  - The activation of cholinergic pathways by nicotine elicits various physiological
      and pharmacological effects in mammals. For example, the stimulation of nicotinic
      acetylcholine receptors (nAChRs) leads to an antinociceptive effect. However, it
      remains to be elucidated which subtypes of nAChR are involved in the
      antinociceptive effect of nicotine on nerve injury-induced allodynia and the
      underlying cascades of the nAChR-mediated antiallodynic effect. In this study, we
      attempted to characterize the actions of nicotine at the spinal level against
      mechanical allodynia in an animal model of neuropathic pain, tibial nerve
      transection (TNT) in rats. It was found that the intrathecal injection of
      nicotine, RJR-2403, a selective alpha4beta2 nAChR agonist, and choline, a
      selective alpha7 nAChR agonist, produced an antinociceptive effect on the TNT
      induced allodynia. The actions of nicotine were almost completely suppressed by
      pretreatment with mecamylamine, a non-selective nicotinic antagonist, or dihydro
      beta-erythroidine, a selective alpha4beta2 nAChR antagonist, and partially
      reversed by pretreatment with methyllycaconitine, a selective alpha7 nAChR
      antagonist. Furthermore, pretreatment with strychnine, a glycine receptor
      antagonist, blocked the antinociception induced by nicotine, RJR-2403, and
      choline. On the other hand, the GABAA antagonist bicuculline did not reverse the
      antiallodynic effect of nicotine. Together, these results indicate that the
      alpha4beta2 and alpha7 nAChR system, by enhancing the activities of glycinergic
      neurons at the spinal level, exerts a suppressive effect on the nociceptive
      transduction in neuropathic pain.

PMID- 16950411
TI  - Inhibition of neuronal nitric oxide synthase causes attenuation of
      cerebrovascular dysfunction in experimental heatstroke.
AB  - The present study was performed to assess the prophylactic effect of 7
      nitroindazole (7-NI), an inhibitor of neuronal nitric oxide synthase (nNOS), in
      an animal model of heatstroke. Anesthetized rats, immediately before the start of
      heat stress, were divided into two major groups and given the following: vehicle
      solution (1 mL per kg body weight) or 7-NI (5-20mg/mL per kg body weight)
      intraperitoneally. They were exposed to ambient temperature of 43 degrees C to
      induce heatstroke. Another group of rats were exposed to room temperature (24
      degrees C) and used as normothermic controls. Their physiologic and biochemical
      parameters were continuously monitored. When the vehicle-pretreated rats
      underwent heat stress, their survival time values were found to be 21-25 min.
      Pretreatment with intraperitoneal doses of 7-NI significantly improved survival
      during heatstroke (55-164 min). As compared to those of normothermic controls,
      all vehicle-pretreated heatstroke animals displayed higher levels of core
      temperature, intracranial pressure, nitric oxide metabolite (NO(2)(-)),
      glutamate, glycerol, lactate/pyruvate ratio, neuronal damage score and nNOS
      expression in the hypothalamus, and tumor necrosis factor-alpha (TNF-alpha) in
      the serum. In contrast, all vehicle-pretreated heatstroke animals had lower
      levels of mean arterial pressure, cerebral perfusion pressure, cerebral blood
      flow, and brain PO(2). Administration of 7-NI before the start of heat exposure
      significantly reduced the hyperthermia, intracranial hypertension, nNOS-dependent
      NO(2)(-), glutamate, glycerol, lactate/pyruvate ratio, and neuronal damage score
      in the hypothalamus, as well as overproduction of TNF-alpha in the serum that
      occurred during heatstroke. The data show that reduction of nNOS-dependent NO(2)(
      ) with 7-NI causes attenuation of cerebrovascular dysfunction, hyperthermia, and
      TNF-alpha overproduction during heatstroke in the rat.

PMID- 16950412
TI  - The influence of aneurysm size on perioperative cardiac outcome in elective open
      infrarenal aortic aneurysm repair.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) size and growth has been found to be
      associated with local generation of inflammation markers such as interleukin-6.
      Inflammation also seems to be important in perioperative adverse cardiac events.
      We hypothesized that patients with a large AAA are at increased risk for cardiac
      events. METHODS: Consecutive patients who underwent a computed tomography
      angiography scan before open elective infrarenal AAA repair between March 2000
      and December 2005 at three hospitals were analyzed. All patients were screened
      for the clinical risk factors of age, gender, angina pectoris, myocardial
      infarction, heart failure, diabetes, stroke, renal failure, and chronic
      obstructive pulmonary disease, as well as for cardioprotective medication.
      Postoperative data on troponin release, creatine kinase/creatine kinase isoenzyme
      MB, and electrocardiogram were routinely collected on days 1, 3, 7, and 30. The
      main outcome measure was the combined end point of 30-day cardiovascular death
      and nonfatal myocardial infarction. Multivariate Cox regression analysis was used
      to evaluate the influence of AAA size on postoperative cardiac outcome. RESULTS:
      The study included 500 patients. Their mean age was 69.8 +/- 9.5 years, and 431
      (86%) were men. Thirty-one patients (6.2%) had perioperative cardiovascular
      complications, consisting of 15 (3.0%) cardiovascular deaths and 16 (3.2%)
      nonfatal myocardial infarctions. After correction for other risk factors,
      including age, Revised Cardiac Risk Index, medication use, duration of surgery,
      and intraoperative blood loss, AAA size was independently associated with
      perioperative nonfatal myocardial infarction and cardiovascular death (3.2%
      increase in risk for each millimeter added, 95% confidence interval 1.1% to 6.2%,
      P = .007). CONCLUSION: A larger AAA size is independently associated with an
      increased incidence of perioperative cardiovascular complications after elective
      infrarenal AAA repair.

PMID- 16950413
TI  - Gastrointestinal complications after descending thoracic and thoracoabdominal
      aortic repairs: a 14-year experience.
AB  - OBJECTIVE: There is a paucity of data regarding gastrointestinal (GI)
      complications after descending thoracic and thoracoabdominal aortic (DTA/TAA)
      surgical repairs. We examined our 14-year experience with these repairs to
      determine the incidence, outcomes, and risk factors for postoperative GI
      complications. METHODS: Between February 1991 and February 2005, we repaired
      1,159 DTA/TAA. Data were prospectively collected. The mean patient age was 68
      years and 36% were women. Complications were classified as biliary disease,
      hepatic dysfunction, pancreatitis, GI bleeding, peptic ulcer disease, bowel
      ischemia, and ileus. Risk factors for the occurrence of GI complications were
      ascertained by univariate and multivariable analysis. RESULTS: Of the 1,159
      patients, 81 had 109 GI complications, for a 7% incidence. The mortality
      associated with GI complications was 39.5% compared with 13.5% (P < .0001) in
      patients without GI complications. The incidences of complications were bowel
      ischemia, 2.5% with 62% mortality; biliary disease, 0.3% with 75% mortality;
      hepatic dysfunction, 1.6% with 38% mortality; acute pancreatitis, 0.3% with 20%
      mortality; GI bleeding, 1.5% with 29% mortality; peptic ulcer disease, 0.9% with
      30% mortality; and ileus, 2.2% with 26% mortality. Postoperative biliary disease
      (odds ratio [OR], 16.58; P = .001), hepatic dysfunction (OR, 3.58; P = .006), and
      bowel ischemia (OR, 10.03; P = .0001) were significantly associated with an
      increased postoperative mortality. Risk factors for the occurrence of GI
      complications were visceral involvement of the aortic repair (TAA extent II, III,
      and IV) (OR, 2.08; P = .002) and low preoperative glomerular filtration rate (OR,
      .98; P = .0002). CONCLUSION: Biliary disease, hepatic dysfunction, and bowel
      ischemia after DTA/TAA surgical repairs were associated with an increased
      mortality. Visceral involvement and preoperative renal insufficiency were risk
      factors for the occurrence of GI complications.

PMID- 16950414
TI  - Endoleaks after endovascular repair of thoracic aortic aneurysms.
AB  - OBJECTIVE: Endoleaks are one of the unique complications seen after endovascular
      repair of thoracic aortic aneurysms (TEVAR). This investigation was performed to
      evaluate the incidence and determinants of endoleaks, as well as the outcomes of
      secondary interventions in patients with endoleaks, after TEVAR. METHODS: Over a
      6-year period, 105 patients underwent TEVAR in the context of pivotal Food and
      Drug Administration trials with the Medtronic Talent (n = 64) and Gore TAG (n =
      41) devices. The medical and radiology records of these patients were reviewed
      for this retrospective study. Of these, 69 patients (30 women and 39 men) had
      follow-up longer than 1 month and were used for this analysis. The patients were
      evaluated for the presence of an endoleak, endoleak type, aneurysm expansion, and
      endoleak intervention. RESULTS: The mean follow-up in this patient cohort was
      17.3 +/- 14.7 months (range, 3-71 months). Endoleaks were detected in 29% (20/69)
      of patients, of which 40% (8/20) were type I, 35% (7/20) were type II, 20% (4/20)
      were type III, and 5% (1/20) had more than one type of endoleak. Patients without
      endoleaks experienced greater aneurysm sac regression than those with endoleaks (
      2.89 +/- 9.1 mm vs -0.13 +/- 7.2 mm), although this difference was not
      statistically significant (P = .232). All but 2 endoleaks (90%; 18/20) were
      detected on the initial postoperative computed tomographic scan at 30 days. Two
      endoleaks (10%; 2/20) developed late. The endoleak group had more extensive
      aneurysms with significantly larger aneurysms at the time of intervention (69.4
      +/- 10.5 mm vs 60.6 +/- 11.0 mm; P = .003). Factors predictive of endoleak
      included male sex (P = .016), larger aneurysm size (P = .003), the length of
      aorta treated by stent grafts (P = .0004), and an increasing number of stents
      used (P < .0001). No open conversions were performed for treatment of endoleaks.
      Four (50%) of the eight type I endoleaks were successfully repaired by using
      endovascular techniques. None of the type II endoleaks was treated by secondary
      intervention. During follow-up, the maximum aneurysm diameter in the type II
      endoleak patients increased a mean of 2.94 +/- 7.2 mm (range, -4.4 to 17 mm).
      Spontaneous thrombosis has occurred in 29% (2/7) of the type II endoleaks.
      Patients with type III endoleaks experienced a decrease in mean maximal aneurysm
      diameter of 0.78 +/- 3.1 mm during follow-up. CONCLUSIONS: Endoleaks are not
      uncommon after TEVAR. Many type I endoleaks may be treated successfully by
      endovascular means. Short-term follow-up suggests that observational management
      of type II endoleaks is associated with continued sac expansion, and these
      patients should be monitored closely.

PMID- 16950415
TI  - An 8-year experience with type II endoleaks: natural history suggests selective
      intervention is a safe approach.
AB  - OBJECTIVE: The treatment of type II endoleaks remains controversial because
      little is known about their long-term natural history and impact on changes in
      aneurysm morphology. This study reviews type II endoleaks occurring in patients
      after endovascular abdominal aortic aneurysm repair (EVAR) at a single
      institution over an 8-year period. METHODS: All patients undergoing EVAR who had
      type II endoleaks documented on follow-up imaging studies at our institution
      between January 1997 and March 2005 were reviewed. Data regarding patient
      demographics in addition to aneurysm size, device type, operative complications,
      and secondary interventions were reviewed. Outcomes evaluated included the rate
      of spontaneous sealing, freedom from secondary intervention, and aneurysm
      enlargement, rupture, or conversion. RESULTS: Type II endoleaks were present in
      154 of 965 patients (16.0%) undergoing EVAR. Mean follow-up time was 22.0 months
      (range, 1 to 72 months). Fifty-five patients (35.7%) with type II endoleaks
      sealed spontaneously in a mean time of 14.5 months. According to Kaplan-Meier
      analysis, approximately 75% of type II endoleaks sealed spontaneously within a 5
      year period. Nineteen patients (12.3%) with type II endoleaks were treated at a
      mean time of 19.9 months at the operating surgeon's discretion, including 13 with
      sac enlargement >5 mm. Kaplan-Meier analysis estimated that approximately 65% of
      the patients remained free of intervention after a period of 4 years. Thirteen
      patients (8.4%) experienced aneurysm sac enlargement >5 mm. Kaplan-Meier analysis
      estimated that approximately 80% of patients with type II endoleaks remained free
      of sac enlargement >5 mm over a 4-year period. No patients with type II endoleaks
      experienced rupture or required conversion to open repair during their follow-up.
      Cox regression analysis showed that cancer, coronary artery disease, and chronic
      obstructive pulmonary disease were associated with earlier spontaneous closure of
      the type II endoleaks (P < .05). CONCLUSIONS: We observed that type II endoleaks
      have a relatively benign course, and in the absence of sac expansion, can be
      followed for a prolonged course of time without the need for intervention. The
      rate of spontaneous seal continues to increase with time and, therefore, close
      follow-up of patients with type II endoleaks who show no signs of aneurysm
      expansion is a safe approach. For patients in whom the exact etiology of their
      endoleak is in question, dynamic imaging should be used to exclude the presence
      of a type I endoleak.

PMID- 16950417
TI  - Combined surgical and endovascular treatment of aortic arch aneurysms.
AB  - BACKGROUND: Traditional repair of aortic arch aneurysms requires cardiopulmonary
      bypass, hypothermia, and circulatory arrest and is associated with considerable
      morbidity and mortality. Endovascular stent-graft placement has developed as a
      safe and effective treatment for various diseases of the descending aorta and,
      recently, even in delicate anatomic regions such as the aortic arch. The aim of
      this study is to review our clinical experience with endovascular treatment of
      aortic arch aneurysms after surgical transposition of supra-aortic vessels.
      METHODS: Fifteen patients received thoracic stent-graft implants after aortic
      debranching for repair of aortic arch aneurysms during the 3-year period ending
      December 31, 2005. All patients were not candidates for standard endovascular
      repair due to inadequate proximal landing zones on the aortic arch. Device design
      and implant strategy were determined by an evaluation of aortic morphology with
      angiography and computed tomography (CT) scanning. Stent-grafts were used to
      repair the arch after supra-aortic vessel transposition was performed. The
      endografts were implanted transfemorally or via an iliac Dacron conduit graft
      using standardized endovascular techniques. Follow-up was 100% complete (mean, 18
      +/- 2.5 months; range, 12 to 36 months). Outcome variables included death and
      treatment failure (endoleak, aortic rupture, reintervention, or aortic-related or
      sudden death). Follow-up included clinical examination, chest radiograph, and CT
      at discharge, 6 months after stent-graft placement, and yearly thereafter.
      RESULTS: Stent-graft deployment success was 100% after staged supra-aortic vessel
      transposition. Patency of all endografts and conventional bypasses was 100%. No
      endoleak or graft migration was observed. There were no neurologic complications.
      One patient died 2 months after the procedure from pulmonary complications.
      CONCLUSION: Repair of aortic arch aneurysms by sequential transposition of the
      supra-aortic branches and endovascular stent-graft placement is feasible.
      Extended application of this technique will enable safe and effective treatment
      of a highly selected subgroup of patients with aortic aneurysms by avoiding
      conventional arch aneurysm repair in deep hypothermia and circulatory arrest.

PMID- 16950418
TI  - An intention-to-treat by endovascular repair policy may reduce overall mortality
      in ruptured abdominal aortic aneurysm.
AB  - OBJECTIVE: The use of endovascular aneurysm repair (EVAR) for ruptured abdominal
      aortic aneurysm (AAA) has been restricted to a small number of specialized units
      on a selected group of patients. The aim of this study is to assess if the
      overall mortality in these patients with ruptured AAA may be reduced in a unit
      where all patients with ruptured AAA are considered first for EVAR. METHODS:
      During a 24-month period beginning in July 2002, 51 patients admitted with
      ruptured AAA were considered for EVAR as the treatment of choice and comprised
      the study group. EVAR was performed in 17 patients. Open repair was performed in
      34 patients: 13 patients had hemodynamic instability and 16 patients had an
      unsuitable aortic neck anatomy. The study group was compared with a historical
      control group of 41 patients with ruptured AAA who were treated by open repair
      from July 2000 to June 2002. RESULTS: Mortality rate was 39% in the study group
      compared with 59% in the control group (P = .065). The duration of stay in the
      intensive care unit was significantly lower in the study group than in the
      control group (P = .01), although the total in-hospital stay was similar (17 days
      vs 14 days, P = .83). Within the study group, EVAR patients had a mortality rate
      of 24% compared with 47% in the open group (P = .14). CONCLUSION: Although the
      number of patients was small, offering EVAR to as many patients as possible with
      ruptured AAA has resulted in a 20% reduction in mortality, albeit statistically
      insignificant. However, it is in the unstable patients that EVAR will need to
      improve survival before it may be hailed to supersede the conventional approach.

PMID- 16950419
TI  - Noninvasive investigation of autonomic activity after carotid stenting or carotid
      endarterectomy.
AB  - OBJECTIVE: Carotid artery stenting (CAS) has been introduced as an alternative to
      carotid endarterectomy (CEA) for the treatment of carotid artery stenosis. Both
      techniques seem to be associated with postoperative hemodynamic lability. Both
      may induce baroreceptor dysfunction, possibly leading to transient impairment of
      cardiovascular autonomic activity and resulting in hemodynamic instability. This
      instability might contribute to postoperative morbidity. To elucidate these
      phenomena, we studied the cardiac baroreflex and autonomic cardiovascular control
      after CAS and CEA. METHOD: In 20 patients scheduled for CAS (n = 10) or CEA (n =
      10), intra-arterial pressures and electrocardiograms were recorded during 10
      minutes before and 8 and 24 hours after the procedure. Spontaneous cardiac
      baroreflex sensitivity was assessed using the sequence method and cross-spectral
      analysis. In addition, cardiovascular autonomic activity was investigated using
      spectral analysis of heart rate variability and systolic arterial pressure
      variability. RESULTS: After CAS, we demonstrated an increase of the spontaneous
      baroreflex sensitivity median (interquartile range) from 5.6 (5.1 to 6.2) ms/mm
      Hg before the procedure to 8.8 (6.8 to 10.5) ms/mm Hg and 7.7 (3.9 to 8.6) ms/mm
      Hg (P < .001), 8 and 24 hours after the procedure. This was consistent with the
      increase of the high frequency component of heart rate variability reflecting
      cardiac parasympathetic activity and a decrease of the low frequency of systolic
      arterial pressure variability reflecting sympathetic vascular activity. The
      postoperative period was also associated with decreased systolic arterial
      pressure from 173 (162 to 190) mm Hg at baseline to 122 (109 to 143) mm Hg and
      136 (121 to 143) mm Hg at 8 and 24 hours after CAS (P < .001). No changes in
      baroreflex sensitivity or in autonomic activity were observed after CEA.
      CONCLUSIONS: These preliminary data suggest that CAS is associated with
      parasympathetic predominance postoperatively and may probably explain the lower
      systolic arterial pressure observed after CAS.

PMID- 16950421
TI  - Trends in the in-hospital stroke rate following carotid endarterectomy in
      California and Maryland.
AB  - OBJECTIVE: We examined the outcome of carotid endarterectomy (CEA) in the state
      of Maryland during the last decade to identify any trends in the incidence of in
      hospital stroke and mortality and compared these results with the outcome of the
      operation throughout the state of California as a control population. METHOD: We
      performed a retrospective analysis of 10 years (1994 to 2003) of the Maryland and
      5 years (1999 to 2003) of the California hospital discharge databases. The
      following patients were included in the analysis: (1) International
      Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM)
      procedure code 38.12 (endarterectomy of the vessels of the head and neck other
      than intracranial vessels) in the primary coding position but not in any
      secondary position, or (2) the diagnosis code 433.00 to 433.91
      (occlusion/stenosis, precerebral artery), or (3) the diagnosis-related group
      (DRG) 5 (extracranial vascular procedure). Symptomatic patients were identified
      by history of previous stroke (ICD-9 codes 342 or 438), transient ischemic attack
      (435 or 781.4), or amaurosis fugax (362.34 or 368.12). In-hospital strokes were
      identified by ICD-9 codes 997.0, 997.00, 997.01, and 997.09. Low-, moderate-, and
      high-volume surgeons were defined as performing <15, 15 to 74 and >or=75 CEAs
      annually. Hospital volumes were similarly classified as low for those performing
      <or=20 CEAs, moderate for 21 to 100, and high for >100 annually. RESULTS: In the
      Maryland data, 23,237 CEA cases were identified with 169 in-hospital strokes over
      10 years (0.73%), whereas the 51,331 California CEAs had 232 in-hospital strokes
      over 5 years (0.45%). The stroke rate in Maryland was 2.12% in 1994, 1.47% in
      1995, and 0.29% to 0.65% from 1996 to 2003. The decrease in strokes was more
      pronounced among symptomatic patients, where the rate was 3.82% in 1994, 4.44% in
      1995, and 0.90% to 2.29% from 1996 to 2003. A similar decrease was identified in
      the asymptomatic patient population but was less pronounced: 1.64% in 1994, 0.81%
      in 1995, and 0.15% to 0.44% from 1996 to 2003. The low recent stroke rates were
      confirmed by the California data (0.44% to 0.48% from 1999 to 2003). Changes in
      the death rate for CEA during this time frame have not been as pronounced, from
      0.33% to 0.58% for Maryland and 0.78% to 0.91% for California. CONCLUSIONS: A
      dramatic decrease in the in-hospital stroke rates in Maryland occurred around
      1995. The stroke rates in Maryland in the past 5 years are similar to those in
      California during the same period. An analysis of data from the two states shows
      that the in-hospital stroke rate now for carotid endarterectomy is approximately
      0.54%.

PMID- 16950423
TI  - Duplex ultrasound criteria for femorofemoral bypass revision.
AB  - PURPOSE: This study was conducted to evaluate the impact of duplex ultrasound
      surveillance on the patency of femorofemoral bypasses performed for symptomatic
      peripheral arterial occlusive disease (PAOD). METHODS: A retrospective review was
      conducted of 108 patients (78 men, 30 women) with a mean age of 62 +/- 10 years
      who underwent femorofemoral prosthetic (n = 100) or vein (n = 8) bypass grafting
      for symptomatic PAOD (claudication, 38%; rest pain, 41%; tissue loss, 11%;
      infection, 10%) during a 10-year period. Prior or concomitant inflow iliac artery
      stenting was performed in 26 patients (24%), and a redo femorofemoral bypass was
      performed in 19 patients (18%). Duplex ultrasound surveillance of the
      reconstruction was performed at 6-month intervals to assess patency, graft
      (midgraft peak systolic flow velocity) hemodynamics, and identify inflow or
      outflow stenotic lesions. Repair was recommended for a stenosis with a peak
      systolic velocity (PSV) >300 cm/s and a PSV ratio >3.5. Life-table analysis was
      used to estimate primary, assisted-primary, and secondary graft patency. RESULTS:
      During a mean 40-month follow-up (range, 2 to 120 months), 31 bypasses (29%) were
      revised: 19 duplex-detected stenosis involving the inflow iliac artery (n = 15)
      or anastomotic stenosis (n = 4), or both, 11 for graft thrombosis, and 1 for
      graft infection. Abnormal inflow iliac (PSV >300 cm/s) hemodynamics or a mid
      graft PSV <60 cm/s was measured in eight of 11 grafts before thrombosis. Mean
      time to revision was 30 +/- 17 months. The primary graft patency at 1, 3, and 5
      years was 86%, 78%, and 62%, respectively. Correction of duplex-detected stenosis
      resulted in assisted-primary patency of 95% at 1 year and 88% at 3 and 5 years (P
      < .0001, log-rank). Secondary graft patency was 98% at 1 year and 93% at 3 and 5
      years. CONCLUSIONS: Vascular laboratory surveillance after femorofemoral bypass
      that included duplex ultrasound imaging of the inflow iliac artery and graft
      accurately identified failing grafts. A duplex-detected identified stenosis with
      a PSV >300 cm/s correlated with failure, and repair of identified lesions was
      associated with excellent 5-year patency.

PMID- 16950425
TI  - Peripheral atherectomy in TransAtlantic InterSociety Consensus type C
      femoropopliteal lesions for limb salvage.
AB  - BACKGROUND: The optimal therapy for TransAtlantic Societal Consensus (TASC) type
      C femoropopliteal lesions remains a critical issue in the treatment of
      infrainguinal occlusive disease. The purpose of this study was to evaluate the
      outcome of limbs with TASC C femoropopliteal lesions and critical limb ischemia
      treated with the FoxHollow SilverHawk atherectomy catheter. METHODS: From
      September 2004 to September 2005, 18 consecutive femoropopliteal procedures
      performed in 17 limbs in 16 patients were reviewed. Demographic data, baseline
      angiographic findings, and indications for the procedures were recorded. Clinical
      outcomes including symptom resolution and limb salvage were determined for the 17
      primary procedures. Hemodynamic improvement was compared by using the paired
      Student t test. Stenosis-free patency was determined by the Kaplan-Meier method.
      RESULTS: The mean age was 72.5 years (range, 47-88 years). Fifty percent of the
      patients had four or more of the following risk factors: hypertension, diabetes,
      tobacco use, hyperlipidemia, renal insufficiency, and coronary artery disease.
      The indication was tissue loss in 13 limbs and rest pain in 4. All patients had a
      second level of disease, either inflow or tibial/pedal, which was treated
      concurrently when appropriate. Initial resolution of symptoms was achieved in 12
      limbs, and partial healing was achieved in 2 others. Early amputation was
      necessary in the remaining three patients, but this was likely due to severe
      inframalleolar disease and advanced forefoot ischemia at the time of
      presentation. Five patients have remained symptom-free without restenosis at a
      mean follow-up of 6 months. Two patients have required late amputation for
      hemodynamic failure. The ankle-brachial index improved from 0.39 +/- 0.08 (mean
      +/- SEM) before surgery to 0.75 +/- 0.08 in the immediate postoperative period (P
      = .02). However, it returned toward baseline at 6 months after surgery, with a
      mean of 0.48 +/- 0.07. Stenosis-free patency of the femoropopliteal segment was
      22% at 12 months. CONCLUSIONS: Peripheral atherectomy can achieve good early
      clinical and hemodynamic success in patients with TASC C lesions and critical
      limb ischemia. However, mid-term restenosis rates are high in this challenging
      cohort of patients.

PMID- 16950427
TI  - Meta-analysis of femoropopliteal bypass grafts for lower extremity arterial
      insufficiency.
AB  - BACKGROUND: In femoropopliteal bypass surgery, the use of saphenous vein grafts
      is preferable, but synthetic grafts are widely used above the knee. The objective
      of this meta-analysis was to assess the long-term patency of femoropopliteal
      bypass grafts classified as above-knee polytetrafluoroethylene, above-knee
      saphenous vein, or below-knee saphenous vein. METHODS: Studies published from
      1986 through 2004 were identified from electronic databases and reference lists;
      73 articles contributed 1 or more series that used survival analysis, assessed
      femoropopliteal bypasses in one of the foregoing configurations, reported a 1
      year graft patency rate, and included at least 30 bypasses. The series with a
      predominance of claudicant patients were included in meta-analysis C, and the
      series in which critical ischemia predominated were included in meta-analysis CI.
      Pooled survival curves of graft patency were constructed. RESULTS: In meta
      analysis C, the pooled primary graft patency was 57.4% for above-knee
      polytetrafluoroethylene, 77.2% for above-knee vein, and 64.8% for below-knee vein
      at 5 years; there was a significant difference between above-knee grafts at 3, 4,
      and 5 years (P < .05). The corresponding pooled secondary graft patency was
      73.2%, 80.1%, and 79.7%, respectively (P > .05). In meta-analysis CI, the pooled
      primary graft patency was 48.3% for above-knee polytetrafluoroethylene, 69.4% for
      above-knee vein, and 68.9% for below-knee vein at 5 years; there was a
      significant difference between above-knee grafts until 4 years (P < .05). The
      corresponding pooled secondary graft patency was 54.0%, 71.9%, and 77.8%,
      respectively, with a significant difference between above-knee grafts at 2, 3,
      and 4 years (P < .05). CONCLUSIONS: The great saphenous vein performs better than
      polytetrafluoroethylene in femoropopliteal bypass grafting and should be used
      whenever possible.

PMID- 16950428
TI  - Systematic review of preservation methods and clinical outcome of infrainguinal
      vascular allografts.
AB  - OBJECTIVE: We systematically reviewed clinical studies on the use of venous and
      arterial allografts for infrainguinal revascularization. We attempted to find
      evidence for the best infrainguinal vascular allograft by a systematic review of
      the available literature. METHODS: An electronic search of the MEDLINE, EMBASE,
      and Cochrane databases was used to determine key articles from studies on the
      different types of vascular allografts used in infrainguinal reconstruction from
      1966 to 2004. Articles were independently reviewed by using previously defined
      inclusion and exclusion criteria. Study results were gathered with cumulative
      primary patency as the primary end point. Secondary end points were major
      complications, graft disintegration, and major limb loss. Quantitative analysis
      was performed on the prospective randomized trials, and linear regression
      analysis was performed on cumulative primary patency. Fontaine's classification
      system was applied. RESULTS: No systematic review of randomized controlled trials
      was found. Five randomized controlled trials, 3 prospective cohort or case
      series, and 15 retrospective case series with 3,837 vascular allografts were
      found. Methods of allograft preservation were cryopreservation (5 studies), cold
      storage (3 studies), and glutaraldehyde preservation of human umbilical veins (15
      studies). One-year cumulative primary patency rates were 13% to 79% for
      cryopreservation, 63% to 80% for cold storage, and 40% to 91% for glutaraldehyde.
      The weighted mean 1-year cumulative primary graft patency rate was 41% for
      cryopreservation, 71% for cold storage, and 70% for glutaraldehyde allografts.
      Four randomized trials on femoropopliteal bypasses demonstrated higher patency
      rates of glutaraldehyde-preserved human umbilical veins than
      polytetrafluoroethylene grafts. Statistical heterogeneity between studies (I(2) =
      91.4%) was too high to perform a formal meta-analysis. The rate of major limb
      loss was 20% to 58% for cryopreservation, 10% to 69% for cold storage, and 0% to
      65% for glutaraldehyde, and the percentage of graft disintegration was 2% to 6%
      for cryopreservation, 4% to 15% for cold storage, and 0% to 11% for
      glutaraldehyde. CONCLUSIONS: A firm conclusion could not be made because there
      were no studies available in which direct comparison was performed between
      different preservation methods of vascular allografts. In addition, heterogeneity
      of the individual studies hampered direct comparison of different types of
      vascular allografts. However, the overall graft performance of glutaraldehyde
      preserved human umbilical vein allografts may be superior to that of other
      vascular allografts.

PMID- 16950429
TI  - Imbalance between nitric oxide generation and oxidative stress in patients with
      peripheral arterial disease: effect of an antioxidant treatment.
AB  - BACKGROUND: Nitric oxide (NO), a potent vasodilator produced by endothelial
      cells, is reduced in patients with peripheral arterial disease (PAD), but the
      mechanism has not been fully elucidated. Because NO is rapidly inactivated by
      superoxide anion, we speculated that enhanced oxidative stress could lower NO
      generation. The aim of our study was to investigate if an imbalance between
      oxidative stress and NO does exist in patients with PAD and if an increase of NO
      formation could be achieved by an antioxidant treatment. METHODS: In a first
      study, serum levels of nitrite and nitrate (NOx), markers of NO generation, and 8
      hydroxy-2-deoxyguanosine (8-OHdG), a marker of oxidative stress and maximal
      walking distance (MWD), were measured in 40 PAD patients and 40 controls. In a
      second study, 10 PAD patients were randomly allocated in a crossover design to
      intravenous propionyl-L-carnitine (6 g/day) or placebo for 7 days, with a washout
      of 30 days between the two phases of the trial. Serum levels of NOx and 8-OHdG
      were measured before and after the study. RESULTS: Compared with controls, serum
      levels of 8-OHdG (mean +/- SD) were significantly increased in PAD patients (4.4
      +/- 3.1 ng/mL vs 2.4 +/- 1.2 ng/mL; P < .001), and serum levels of NOx were
      significantly decreased (11.6 +/- 6 microM vs 17 +/- 6.1 microM; P < .001).
      Levels of 8-OHdG and NOx were inversely correlated (r = -0.879; P < .001). Serum
      levels 8-OHdG were inversely correlated with MWD (r = -0.48, P = .002). The
      interventional trial showed no changes in the patients given placebo. Patients
      treated with propionyl-L-carnitine showed a significant increase of MWD from 101
      +/- 31 meters to 129 +/- 35 meters (P = .007) and in NOx from 14.5 +/- 4.5 microM
      to 17.1 +/- 3.8 microM (P = .007). A significant decrease of 8-OHdG from 3.6 +/-
      1.1 ng/mL to 2.6 +/- 1 ng/mL was also found (P = .005.) CONCLUSIONS: This study
      suggests that in PAD patients, the reduction of NO generation could be dependent
      upon enhanced oxidative stress.

PMID- 16950430
TI  - A modified calculation of ankle-brachial pressure index is far more sensitive in
      the detection of peripheral arterial disease.
AB  - BACKGROUND: Ankle-brachial pressure index (ABI) is a simple, inexpensive, and
      useful tool in the detection of peripheral arterial occlusive disease (PAD). The
      current guidelines published by the American Heart Association define ABI as the
      quotient of the higher of the systolic blood pressures (SBPs) of the two ankle
      arteries of that limb (either the anterior tibial artery or the posterior tibial
      artery) and the higher of the two brachial SBPs of the upper limbs. We
      hypothesized that considering the lower of the two ankle arterial SBPs of a side
      as the numerator and the higher of the brachial SBPs as the denominator would
      increase its diagnostic yield. METHODS: The former method of eliciting ABI was
      termed as high ankle pressure (HAP) and the latter low ankle pressure (LAP). ABI
      was assessed in 216 subjects and calculated according to the HAP and the LAP
      method. ABI findings were confirmed by arterial duplex ultrasonography. A
      significant arterial stenosis was assumed if ABI was <0.9. RESULTS: LAP had a
      sensitivity of 0.89 and a specificity of 0.93. The HAP method had a sensitivity
      of 0.68 and a specificity of 0.99. McNemar's test to compare the results of both
      methods demonstrated a two-tailed P < .0001, indicating a highly significant
      difference between both measurement methods. CONCLUSIONS: LAP is the superior
      method of calculating ABI to identify PAD. This result is of great interest for
      epidemiologic studies applying ABI measurements to detect PAD and assessing
      patients' cardiovascular risk.

PMID- 16950431
TI  - Surgical revascularization of renal artery after complicated or failed
      percutaneous transluminal renal angioplasty.
AB  - PURPOSE: The purpose of this study was to evaluate the feasibility and
      effectiveness of surgical reconstruction of the renal artery after complicated or
      failed percutaneous transluminal renal angioplasty (PTRA). METHODS: This was a
      retrospective study of 45 consecutive patients who were referred to our centers
      for surgical renal artery reconstruction after 52 complicated or failed PTRA
      procedures performed between 1980 and 2003. There were 27 women and 18 men, with
      a median patient age of 28 years (25th percentile, 13.5 years; 75th percentile,
      59.5 years). The mean number of PTRA per artery per patient was 1.4 +/- 0.6.
      Renal artery stenosis was due to arterial fibrodysplasia in 25 patients,
      atherosclerosis in 17, and inflammatory arteritis in three. RESULTS: Forty-eight
      renal artery revascularizations were performed (3 bilateral). The procedure
      consisted of in situ surgery in 38 patients (79%) and extracorporeal repair in 10
      (21%). Primary nephrectomy was required in three patients. One patient did not
      undergo surgical repair after failed PTRA because of kidney atrophy. Major
      technical problems were encountered during surgical revascularization in 14 (74%)
      of the 19 patients treated after complicated PTRA and in four (12%) of the 33
      patients treated after failed PTRA. Multiple organ failure led to one death on
      postoperative day 90 in a patient with atherosclerosis and severe kidney
      insufficiency. Postoperative thrombosis of the repaired renal artery led to
      kidney loss in three patients, but only one patient required secondary
      nephrectomy. Primary patency for the overall series of renal revascularizations
      was 93.5% +/- 6.5% at 5 years. CONCLUSION: Surgical reconstruction after
      complicated or failed PTRA is feasible and effective and allows kidney salvage in
      most patients. Technical problems during surgical revascularization may require
      extracorporeal repair in some patients. The results of this study underline the
      need for careful patient selection and skillful PTRA technique.

PMID- 16950432
TI  - Risk factors for leg length discrepancy in patients with congenital vascular
      malformation.
AB  - OBJECTIVES: This study was conducted to determine the clinical risk factors for
      the development of leg length discrepancy (LLD) in patients with congenital
      vascular malformation (CVM) affecting the lower extremity. METHODS: A
      retrospective analysis was conducted of a prospectively collected database that
      included 361 patients who underwent assessment of a CVM lesion from September
      1994 to January 2005. We measured LLD using lower extremity scanograms of 229
      patients who were suspected of having LLD on physical examination. The risk
      factor analysis for a clinically significant LLD (>2 cm) was performed with the
      variables of age, gender, features of CVM (type, extent and depth), and the deep
      vein status (agenesis, hypoplasia, phlebectasia) of the affected limb. Fisher's
      exact test and the chi(2) test were used for the univariate analysis, and a
      logistic regression test was performed for the multivariate analysis. Among the
      patients with LLD, we compared the overgrowth group and undergrowth group with
      the Fisher's exact test to identify differences between the two subgroups.
      RESULTS: The included patients were 153 males (42%) and 208 females (57%) with a
      mean age of 20 +/- 14 years (range, 1 to 62). There were 157 patients (43%) in
      the still growing age group (age <15 years) and 204 (57%) were in the finished
      growing age group (age >15 years). The types of CVMs included 215 venous (60%),
      43 arteriovenous (12%), 46 lymphatic (13%), and 57 (16%) combined venolymphatic
      malformations. On the lower extremity scanogram, 26 patients (7%) had a LLD of >2
      cm due to overgrowth (n = 20) or undergrowth (n = 6) of the affected limbs. The
      univariate analysis showed that a venolymphatic malformation (P = .003) and a
      whole leg CVM (P = .000) were significant risk factors for development of LLD.
      However, the multivariate analysis identified the whole leg CVM lesion as a
      single independent risk factor for LLD (P = .004; odds ratio, 6.512, 95%
      confidence interval, 1.788 to 23.713). On subgroup analysis, a whole leg CVM was
      also identified as a risk factor for overgrowth of the affected limb. In a
      comparison between two subgroups of LLD (overgrowth v. undergrowth), overgrowth
      was significantly (P = .022) more common in female than in male patients.
      CONCLUSIONS: As a clinical risk factor for development of LLD, the extent of the
      CVM lesion was a single independent risk factor regardless of the type or depth
      of the CVM lesion. In addition, our data suggest that overgrowth or undergrowth
      of the affected limb, as a cause of LLD, might be related to gender.

PMID- 16950433
TI  - Influence of gene polymorphisms in ulcer healing process after superficial venous
      surgery.
AB  - OBJECTIVE: Role of superficial venous surgery in reducing the time it takes for
      ulcers to heal is still controversial, although all studies confirm a significant
      reduction in ulcer recurrences. Recently, the HFE-C282Y and FXIII-V34L gene
      variants demonstrated a role in the risk of venous ulceration in primary chronic
      venous disorder (CVD) and in modulating lesion size in chronic venous ulcer
      (CVU), respectively. This study was conducted to investigate the role of HFE
      C282Y and FXIII (V34L and P564L) gene variants in ulcer healing time after
      superficial venous surgery, by assessing the outcome of a cohort of homogeneous
      CVU patients. METHODS: The study selected 91 patients affected by primary CVU
      (CEAP C6, Ep, Asp, Pr), with the exclusion of any other comorbidity factor
      involved in delayed healing process, who underwent surgery. We assessed the ulcer
      area and the healing time. Patients were genotyped by polymerase chain reaction
      for FXIII (V34L and P564L) and for HFE-C282Y substitutions. RESULTS: Globally,
      CVU cases had a postoperative mean healing time of 8.5 +/- 5.7 weeks. For the
      subset of cases above and below the median value (M = 8.0 weeks), FXIII-V34L
      genotype distribution significantly differed (P < .0001). In addition, Kaplan
      Meier analysis yielded specific healing time profiles for the different FXIII
      V34L classes of genotype (P = .00001), with an increased risk of delayed healing
      for the FXIII-VV genotype (hazard ratio, 4.14; 95% confidence interval, 2.1 to
      8.2; P = .00005). Although FXIII-P54L genotype distributions did not differ,
      homozygous 564LL cases (P = .005) and double carriers for both FXIII variants (P
      < .0001), had a significantly reduced healing time vs wild types. No differences
      in healing time were observed between carriers and noncarriers of the HFE-C282Y
      variant, whereas when these cases were stratified by FXIII-V34L genotypes, the
      L34 carriers had a significantly shorter healing time, irrespective of the HFE
      genotype. CONCLUSION: The FXIII-34L variant was significantly associated with
      shorter healing time after superficial venous surgery, suggesting a role in the
      healing and tissue regeneration phases. Conversely, HFE-C282Y, despite its role
      in ulcer establishment, did not affect the postoperative healing time. In
      perspective, the identification of patients with a poor prognosis may give
      clinicians the opportunity to modify management and to target tailored therapies
      in the view of a new and alternative concept of treatment based on
      pharmacogenomics.

PMID- 16950434
TI  - Conservative versus surgical treatment of venous leg ulcers: a prospective,
      randomized, multicenter trial.
AB  - BACKGROUND: The prevalence of venous leg ulcers is as high as 1% to 1.5%, and the
      total costs of this disease are 1% of the total annual health care budget in
      Western European countries. Treatment modalities are conservative or surgical.
      Subfascial endoscopic perforating vein surgery (SEPS) combined with superficial
      vein ligation is performed in many centers to address vein incompetence in
      patients with chronic venous leg ulcers. Several reports describe good healing
      and low recurrence rates, although a randomized trial to compare surgical
      treatment including SEPS and treatment of the superficial venous system to
      conservative modalities has never been performed. Therefore, a prospective,
      randomized, multicenter trial was conducted to study whether ambulatory
      compression therapy with venous surgery is a better treatment than just
      ambulatory compression therapy in venous leg ulcer patients. METHODS: Patients
      with an active (open) venous leg ulcer (CEAP C6) qualified for the study. The
      study consisted of two treatment groups. All patients were treated by
      standardized ambulatory compression therapy, and half of the patients received
      SEPS. Concomitant superficial venous incompetence was also treated in the second
      group. For allocation to both treatment groups, each patient was assigned by a
      computer program at the randomization center. The primary goal of the study was
      to compare the ulcer-free period during follow-up in both study groups. Secondary
      end points were ulcer healing and recurrence rates. RESULTS: From April 1997
      until January 2001, 200 ulcerated legs (170 patients) were included in the study
      in 12 centers in The Netherlands. A total of 97 ulcers were allocated to the
      surgical group and 103 to the conservative group. Patient characteristics were
      similar in the two treatment groups at baseline, with the exception of a higher
      proportion in the conservative group of diabetes mellitus. Healing rates were 83%
      in the surgical group and 73% in the conservative group (not significant; median
      time to healing, 27 months). Recurrence rates were the same in both treatment
      groups (22% surgical vs 23% conservative). During follow-up of a mean of 29
      months (median, 27 months) in the surgical group and 26 months (median, 24
      months) in the conservative group, we found that in the surgical group, the ulcer
      free rate was 72%, whereas in the conservative group this rate was 53% (P = .11;
      Mann-Whitney test). Patients with recurrent ulceration or medially located ulcers
      in the surgical group had a longer ulcer-free period than those treated in the
      conservative group (P = .02 for both). A first-time ulcer and one of the centers
      also had a positive effect on the ulcer-free period during follow-up (P < .001
      and P = .02), independent of the treatment group. Deep vein incompetence did not
      affect the ulcer-free period. CONCLUSIONS: In conclusion, we suggest that
      patients with medial and/or recurrent ulceration should receive surgery combined
      with ambulatory compression therapy. A dedicated center should provide care for
      those patients.

PMID- 16950437
TI  - Association of 24-hour activity levels with the clinical severity of chronic
      venous disease.
AB  - INTRODUCTION: The pathophysiology underlying the skin changes seen in chronic
      venous insufficiency (CVI) is multifactorial. Sedentary lifestyle and prolonged
      sitting and standing at work have been proposed by some authors to be influential
      in the development of CVI skin changes. This study compared the 24-hour activity
      profiles in patients with different clinical severities of CVI and normal
      controls. METHODS: Patients were classified into groups according to CEAP
      clinical severity classes: mild (C2&C3), moderate (C4) and severe (C5&C6).
      Activity profiles were measured in 60 patients and 15 controls using a Newcastle
      Universities Medical Activity (NUMACT) monitor, which recorded the duration spent
      in supine, sitting, and standing postures as well as duration spent walking and
      the walking intensity over a 24-hour period. Analysis was performed by Kruskal
      Wallis and Mann-Whitney tests and Spearman correlation. RESULTS: Walking
      intensity was significantly different between the controls and patient groups
      during prolonged walking (P < .001). The controls spent significantly more time
      standing in a 24-hour period than any of the CVI clinical groups (P = .036), and
      the percentage time spent sitting was significantly higher in the patient groups
      (P = .025). No significant differences were found in the total number of steps
      taken or total duration spent walking in the 24-hour period between any of the
      groups. CONCLUSION: This study shows that walking intensity is lower in the more
      severe clinical groups and may be influenced by the clinical severity of CVI. The
      study provides evidence that prolonged sitting and reduced standing is associated
      with increased severity of CVI, which may by an effect of the patient's symptoms
      rather than a cause of disease progression.

PMID- 16950436
TI  - Chronic venous leg ulcers benefit from surgery: long-term results from 173 legs.
AB  - OBJECTIVE: The purpose of this retrospective study was to present 7 years of data
      from operations of currently active, chronic venous leg ulcers (CEAP: C6),
      focusing on the short- and long-term effects of healing and recurrence and
      considering concomitant risk factors. METHODS: Between January 1997 and March
      2004, 173 patients (239 legs) with a currently active, chronic venous leg ulcer
      were surgically treated. The surgical procedures included two main steps: (1) the
      surgical interruption of reflux in the superficial and perforating veins to
      reduce venous hypertension in the entire leg and/or the affected area and (2) the
      surgical procedure involving the ulcer. A total of 123 patients (173 legs) who
      came to the follow-up were examined. The follow-up period ranged from 3 months to
      7 years. The data collection integrated a preoperative examination that included
      medical history and clinical diagnoses and incorporated measurements such as body
      mass index, ankle-brachial pressure index, and the neutral position method at the
      follow-up. The function of the veins was measured with duplex ultrasonography.
      Finally, the data were analyzed by using various statistical methods, including
      Kaplan-Meier analysis, Cox regression analysis, and paired t tests. RESULTS:
      Initially, ulcer healing occurred in 87% of the cases (151 legs). A total of 13%
      (22 legs) of the venous ulcers never healed, and recurrent venous ulcers occurred
      in 5% (9 legs). The Kaplan-Meier analyses of ulcer healing showed a healing rate
      of 85% in 6 months for all legs. The mean time of healing was 1.5 months.
      Furthermore, the Kaplan-Meier analyses of ulcer recurrence showed a 1.7% rate of
      recurrence in 6 months for all legs. The 5-year ulcer recurrence rate was 4.6%.
      The mean time of recurrence was 70.4 months. CONCLUSIONS: On the basis of the
      results from the 7 years of data from functional surgery of venous leg ulcers and
      as a result of the outcomes of our study, we recommend surgical treatment of
      venous leg ulcers at any stage. We therefore conclude that surgery is indicated
      before an ulcer is intractable to treatment. In general, our findings are based
      on the understanding and identification of the causes and symptoms of venous
      ulceration and illustrate that standard surgical methods can be applied for the
      therapy of venous leg ulcers at any stage.

PMID- 16950439
TI  - Clinical presentation and venous severity scoring of patients with extended deep
      axial venous reflux.
AB  - BACKGROUND: The objective of this study was to evaluate the prevalence and
      profile of patients presenting with chronic venous insufficiency (class C3-C6)
      and cascading deep venous reflux involving femoral, popliteal, and crural veins
      to the ankle. METHODS: From September 2001 to April 2004, 2,894 patients were
      referred to our center for possible venous disorders. The superficial, deep, and
      perforator veins of both legs were investigated with color duplex scanning. The
      criterion for inclusion in this study was the existence of cascading deep venous
      reflux involving the femoral, popliteal, and crural veins to the ankle whose
      duration had to be longer than 1 second for the femoropopliteal vein and longer
      than 0.5 seconds for the crural vein. The advanced CEAP classification, the
      Venous Clinical Severity Score (VCSS), the Venous Segmental Disease Score
      (reflux; VSDS), and the Venous Disability Score (VDS) were used. RESULTS: Seventy
      one limbs in 60 patients were identified. Eleven limbs (15.5%) were classified as
      C3, 36 (50.7%) as C4, 21 (29.6%) as C5, and 3 (4.2%) as C6. A primary etiology
      was identified in 11 (15.5%) limbs, and a postthrombotic etiology was identified
      in 60 limbs (84.5%). In the latter group, all but four patients were aware that
      they had had a previous deep venous thrombosis. In addition to femoropopliteal
      and calf veins, reflux was present in the common femoral vein in 60 (84.5%), the
      deep femoral vein in 27 (38%), and the muscular calf veins in 62 (87.3%).
      Incompetent perforator veins were identified in 53 (74.6%) limbs. Fifty-one
      (71.8%) limbs had a combination of superficial venous insufficiency (AS(2),
      AS(2,3), AS(4), or their combination) previously treated or present. Of these, 11
      had primary etiology alone, and 40 had a secondary etiology with or without
      primary disease. Means and 95% confidence intervals of the VCSS, VSDS, and VDS
      were 9.72 (8.91-10.53), 7.2 (6.97-7.42), and 1.08 (0.83-1.32), respectively. A
      significant increase in the VCSS and in the VSDS (P < .0001) paralleled the CEAP
      clinical class. The VDS was higher in the C3 and C6 classes but did not reach
      significance. There was a significant link between the pain magnitude in the VCSS
      and the VDS (P < .0001). Severity of pain and high VDS did not depend on the
      wearing of elastic compression stockings. VCSS increased significantly according
      to the presence of an incompetent perforator vein (P < .05) and/or reflux in the
      deep femoral vein (P < .05). CONCLUSIONS: This study confirmed the value of the
      Venous Severity Score as an instrument for evaluation of chronic venous
      insufficiency. A significant increase in the VCSS and VSDS paralleled CEAP
      clinical class; VDS was higher in classes C3 and C6 without reaching
      significance, probably because of the small size of the samples. Some clinical
      and anatomic features need to be clarified to facilitate scoring.

PMID- 16950440
TI  - Decreased incidence of left common iliac vein compression in patients with
      abdominal aortic aneurysms.
AB  - OBJECTIVE: Compression of the left common iliac vein (LCIV) by the right common
      iliac artery is an anatomic variant that may increase the risk for LCIV
      thrombosis. The incidence of LCIV compression in patients with abdominal aortic
      aneurysms (AAA) is unknown, however. The aim of this descriptive anatomic study
      was to determine (1) the incidence of LCIV compression in patients with and
      without AAA and (2) if endovascular AAA repair acutely alters the incidence of
      LCIV compression and, hence, the risk of LCIV thrombosis. METHOD: A retrospective
      analysis of medical records and helical computed tomography (CT) scans was
      conducted in 100 AAA patients and 100 non-AAA patients (n = 200). Medical records
      were reviewed for symptoms and risk factors for deep vein thrombosis, and data
      were reported according to the Joint Society Reporting Standards for acute lower
      extremity venous thrombosis. The minor diameters of the aorta, inferior vena
      cava, and common iliac arteries and veins were measured. For AAA patients,
      measurements were obtained from preoperative and 30-day postoperative CT scans.
      RESULTS: The mean age of the study cohort was 38 years (range, 17 to 85 years)
      for non-AAA subjects and 73 years (range, 51 to 89 years) for AAA subjects. The
      mean acute lower-extremity venous thrombosis risk factor score was low for both
      patient groups (non-AAA, 0.82 +/- 0.12; AAA, 2.63 +/- 0.14). Mean compression of
      the LCIV was 37.8% (range, 0% to 74.8%) for non-AAA patients but only 27.3%
      (range, 0% to 74.2%; P < .0006) for AAA patients. Of non-AAA patients with venous
      compression, the right common iliac artery was the compressing structure in 87%
      of cases. However, of AAA patients with venous compression, the left common iliac
      artery was the compressing structure in 76% of cases. There was no statistically
      significant change in the degree of compression of the LCIV before and after
      endovascular repair (27.3% vs 25.1%, respectively) nor was there a change in the
      structure that compressed the LCIV. CONCLUSION: Patients with AAA were found to
      have more tortuous iliac arteries that led to less anatomic compression of the
      LCIV compared with nonaneurysmal patients. Furthermore, the left common iliac
      artery was found to compress the LCIV in most of the AAA patients, and the right
      iliac artery was found to compress the LCIV in most non-AAA patients.
      Endovascular AAA repair did not acutely alter these anatomic findings. Patients
      with AAA may therefore be at lower risk of developing LCIV thrombosis owing to
      the nature of their anatomy.

PMID- 16950441
TI  - Endovenous ablation of the great saphenous vein may avert phlebectomy for branch
      varicose veins.
AB  - BACKGROUND: Endovenous ablation of the great saphenous vein (GSV) may be
      performed simultaneously with stab phlebectomy of branch varicose veins or as a
      stand-alone procedure. A clinical approach of performing radiofrequency ablation
      (RFA) alone as initial treatment for varicose veins was reviewed. METHODS:
      Patients with duplex ultrasound-documented reflux in the GSV and CEAP clinical
      stage 2 to 6 were selected for RFA. Patients were examined within a week
      preoperatively with duplex ultrasound imaging. Patients were seen within a week
      postoperatively and again at 2 to 3 months to ascertain if further treatment was
      required. A retrospective review of the initial 184 procedures in a series from
      June 2002 through February 2005 was performed, allowing for a 9-month follow-up
      period. RESULTS: Three procedures were performed under general anesthesia and 181
      with intravenous sedation and tumescent anesthesia. Postoperative duplex scans
      showed total occlusion or partial patency of <10 cm in 155 limbs. Seven (4.5%)
      had concomitant stab phlebectomy, seven subsequently had sclerotherapy, and 39
      (25.2%) underwent subsequent stab phlebectomy of persistent symptomatic
      varicosities. In 101 limbs (65.1%), symptoms resolved and had no further therapy,
      and 24 limbs had a GSV that was patent for >10 cm on postoperative duplex
      imaging. Nine limbs had no further therapy (37.5%), eight (33.3%) had subsequent
      stab phlebectomy, and three had stripping of the GSV and stab phlebectomy. Four
      limbs had a redo RFA, four limbs had an aborted RFA procedure, and one limb was
      lost to follow-up. Failure of total GSV occlusion was more often associated with
      use of a 6F catheter. Complications were generally mild, and there was no
      postoperative deep vein thrombosis. CONCLUSION: Endovenous ablation of the GSV
      can be performed safely and effectively as the initial treatment for lower
      extremity varicose veins. Because most patients show clinical improvement after
      RFA, an algorithm of reassessment of the limb and branch varicose veins several
      months post-RFA allows most patients to defer stab phlebectomy.

PMID- 16950442
TI  - A comparison of the changes in generic quality of life after superficial venous
      surgery with those after laparoscopic cholecystectomy.
AB  - BACKGROUND: Superficial venous surgery (SVS) results in a significant improvement
      in generic health-related quality of life (HRQL). However, it is unclear how this
      improvement compares with that observed after other commonly performed general
      and vascular operations. The aim of this study was to compare the changes in
      generic HRQL observed before and after SVS for CEAP clinical grade 2 to 4 venous
      disease with those observed before and after elective laparoscopic
      cholecystectomy (ELC) for biliary colic. METHODS: The Short Form 12 questionnaire
      was mailed to patients before and 3, 6, and 12 months after SVS (n = 143) and ELC
      (n = 60). The responses were used to calculate physical (PCS) and mental (MCS)
      component summary scores at each time point. A higher score indicates a better
      HRQL. RESULTS: Before surgery and 3 and 12 months after surgery, patients in the
      ELC group had a significantly lower PCS than those in the SVS group (40.2 vs
      49.5, 48.9 vs 53.1, and 45.4 vs 53.8; P < .001, P = .033, and P < .001,
      respectively; Mann-Whitney U test). However, the change in PCS observed over the
      first 12 postoperative months was not significantly different between the SVS and
      ELC groups. Patients in the ELC group had a significantly lower MCS than those in
      the SVS group before surgery (45.9 vs 50.8; P = .002; Mann-Whitney U test), but
      not after surgery. There was no difference between the two groups in terms of
      postoperative change in MCS. CONCLUSIONS: SVS is associated with a statistically
      significant and clinically meaningful improvement in generic HRQL that is similar
      to that observed after ELC. These novel data lend further support to the clinical
      benefit of SVS and will help health care purchasers make decisions regarding the
      prioritization of vascular and general surgical services.

PMID- 16950443
TI  - The nonsaphenous vein of the popliteal fossa: prevalence, patterns of reflux,
      hemodynamic quantification, and clinical significance.
AB  - BACKGROUND: A large tortuous vein coursing over the posterior aspect of the knee
      and the upper calf may give rise to a constellation of varicose veins unrelated
      to the great (GSV) or small (SSV) saphenous veins. Designated the popliteal fossa
      vein (PFV), it perforates the deep popliteal fascia and empties into the deep
      system. We examined the prevalence, anatomic reflux patterns, hemodynamic role,
      and clinical significance of the PFV. METHODS: We examined 543 patients (818
      limbs) with venous disease, aged 14 to 94 years (median, 55 years). The study
      consisted of group A, comprising limbs with a PFV, and group B, formed by the
      remaining limbs. The history, clinical examination, and venous duplex scan
      findings were analyzed retrospectively. Venous clinical severity and venous
      segmental disease scores of group A were compared with those of an equal number
      of CEAP-, sex-, and age-matched control limbs. In situ venous hemodynamics of the
      PFV obtained with duplex scan are reported. RESULTS: A PFV was found in 24
      (2.93%) of 818 limbs (95% confidence interval [CI], 1.8%-4.1%); 24 (4.4%) of 543
      subjects (95% CI, 2.7%-6.2%), 12 men and 12 women aged 23 to 82 years (median, 54
      years) had a PFV. CEAP clinical classes in limbs with a PFV were as follows: C2,
      15 limbs; C3, 5 limbs; C4, 2 limbs; C5, 1 limb; and C6, 1 limb. Proximal and
      distal (92%), superficial (100%), perforator (87.5%), and complex-pattern (41.7%)
      reflux occurred more often in group A (P < .01). Incompetence in the GSV (75%),
      posterior arch, and posteromedial and saphenous tributaries was also more
      frequent in group A (P < .05). SSV reflux in group A (29%) matched that in group
      B. The PFV terminated at the deep system (96% in the popliteal vein) above the
      SSV (median distance, 1.5 cm; 95% CI, 0.5-2 cm). The odds ratio for a PFV in
      limbs with prior SSV disconnection was 5.68. Deep reflux was evenly distributed
      in group A (41.7%) and group B (27%). The prevalence of incompetent perforators
      was 283% (95% CI, 194%-373%) in group A and 96% (95% CI, 95%-98%) in group B (P <
      .001). PFV tributaries were distributed at the popliteal area (100%); the
      posterior (87.5%), medial (62.5%), and lateral (37.5%) upper calf; and the
      posterior distal thigh (17%), often projecting to the posterior GSV arch (50%).
      The (median) peak velocity of reflux in the PFV was 82.6 cm/s, the mean velocity
      was 17.7 cm/s, the duration was 2.4 seconds, the volume flow was 231.5 mL/min,
      and the expelled volume was 9.3 mL. The median diameter of the PFV at the
      crossing of the fascia was 0.527 cm. Venous clinical severity (range, 2-17;
      median, 5.5) and venous segmental disease (range, 0.5-8; median, 2.75) scores in
      limbs with a PFV exceeded (P <or= .04) those of the control limbs. CONCLUSIONS:
      With a prevalence of 4.4%, the PFV presents in limbs featuring complex reflux
      patterns involving all three venous systems proximally and distally. Limbs with a
      PFV have a higher propensity for GSV and superficial tributary reflux and have
      perforator vein incompetence three times more often than limbs without this vein.
      The PFV perforates the deep popliteal fascia terminating at the deep system (ie,
      the popliteal vein in 96%) distinctly above the SSV. In light of its reflux
      dynamics, nearing or exceeding those of severely impaired perforator veins, and
      the complex patterns of reflux (venous segmental disease) and venous clinical
      severity (high venous clinical severity scores) of the affected limbs, clinical
      and investigational awareness of the PFV is warranted.

PMID- 16950444
TI  - Clinical outcome and complications of temporary inferior vena cava filter
      placement.
AB  - OBJECTIVE: We evaluated the current clinical experience of temporary inferior
      vena cava (IVC) filter placement and its related complications. METHODS: From
      January 2000 to December 2005, we enrolled 33 patients (8 men and 25 women) who
      underwent percutaneous insertion of a temporary IVC filter in the Department of
      Vascular Surgery of Tokyo University Hospital. Deep vein thrombosis (DVT) was
      proven in 78.8% of the patients. The indications for filter insertion were
      contraindication to anticoagulation therapy (9.1%), thrombolytic therapy (12.1%),
      perioperative prophylactic implantation (84.8%), pregnancy with DVT (3.0%), and
      prophylactic implantation in the absence of DVT (15.2%). A Neuhaus Protect was
      used in 13 patients, and an Antheor was used in 20 patients. RESULTS: The mean +/
      SD duration of filter placement was 10.6 +/- 7.0 days. There was no case of
      pulmonary embolism during filter protection and retraction. Filter thrombosis
      (capture of thrombus) was observed in four patients (12.1%), who then received
      additional thrombolytic therapy. Thrombi were dissolved by thrombolysis in three,
      one of whom had replacement with a permanent filter. The thrombus was not
      dissolved in one patient and was removed under venotomy at the insertion site.
      Major filter-related complications occurred in nine patients (27.3%), including
      filter dislocation in four patients (12.1%), catheter fracture in three (9.1%),
      and catheter-related infection in one (3.0%). In a patient with giant ovarian
      cancer, the IVC was nearly occluded with massive thrombus around the filter 2
      days after operation, and the vena cava was then ligated under open laparotomy.
      No patients died during filter protection and retraction. CONCLUSIONS: Temporary
      IVC filters were effective for the prevention of fatal pulmonary embolism.
      However, our experience of a high incidence of complications related to temporary
      filters suggests that this device has limited indications and supports the need
      for innovative design of temporary filters.

PMID- 16950445
TI  - Treatment with an oral small molecule inhibitor of P selectin (PSI-697) decreases
      vein wall injury in a rat stenosis model of venous thrombosis.
AB  - BACKGROUND: Vein wall injury after thrombosis is multifactorial but seems
      dependent on thrombus and local thrombotic and inflammatory mechanisms. We
      hypothesized that inhibition of vein wall injury through reduction of thrombotic
      and inflammatory events with P-selectin inhibition and/or low-molecular-weight
      heparin (LMWH) occurs independently of thrombus resolution in a rat model of
      venous thrombosis. METHODS: Male rats underwent inferior vena cava (IVC) stenosis
      (94.4% +/- 0.5% reduction in IVC diameter) to induce thrombosis. Rats were
      treated from 2 days after thrombosis until they were killed 7 days later. Groups
      consisted of (1) PSI-697, a P-selectin inhibitor (30 mg/kg; oral gavage daily);
      (2) LMWH-Lovenox (LOV; enoxaparin) 3 mg/kg subcutaneously daily; (3) PSI-697 (30
      mg/kg; oral gavage daily) plus LOV 3 mg/kg subcutaneously daily (PSI + LOV); (4)
      and untreated controls. Evaluations included thrombus mass, vein wall tensiometry
      (stiffness [inverse of compliance]), intimal thickness scoring by light
      microscopy, vein wall inflammatory mediators by enzyme-linked immunosorbent
      assay, and vein wall inflammatory cells by histologic evaluation. RESULTS:
      Thrombus mass was not reduced by any treatment. Animals treated with PSI-697
      alone, LOV alone, or PSI + LOV demonstrated significant decreases in vein wall
      stiffness when compared with controls. The vein wall stiffness of the PSI-697
      treated groups was also significantly lower than in the LOV-only group. Animals
      treated with PSI-697 showed a significantly decreased intimal thickness score
      when compared with vehicle control IVCs. Vein wall intimal thickening was also
      significantly decreased in animals treated with PSI-697 vs LOV. The PSI-697 and
      PSI + LOV groups manifested significant decreases in the immunoregulatory and
      inflammatory cytokine interleukin 13 as compared with controls and LOV. Vein wall
      monocyte chemotactic protein 1 levels were also significantly reduced in the PSI
      697 and PSI + LOV groups vs control. Only PSI-697 significantly decreased vein
      wall levels of platelet-derived growth factor betabeta. Both the LOV and PSI +
      LOV groups had significant increases in vein wall monocytes and total
      inflammatory cells vs controls. CONCLUSIONS: These data suggest that both LMWH
      and PSI-697 inhibit vein wall injury independently of thrombus mass. P-selectin
      inhibition seemed superior to LMWH in measured parameters of injury and mediator
      inhibition.

PMID- 16950446
TI  - Controlled release of small interfering RNA targeting midkine attenuates intimal
      hyperplasia in vein grafts.
AB  - OBJECTIVE: Intimal hyperplasia is a major obstacle to patency after vein
      grafting. Despite of a diverse array of trials to prevent it, a satisfactory
      therapeutic strategy for clinical use has not been established. However,
      sufficient inhibition of early stages of intimal hyperplasia may prevent this
      long-term progressive disease. Midkine (MK) is a heparin-binding growth factor
      that was originally discovered as the product of a retinoic acid-responsive gene.
      We previously demonstrated that MK-deficient mice exhibit a striking reduction of
      neointima formation in a restenosis model, which is reversed on systemic MK
      administration. In this study, we evaluated a strategy of using small interfering
      RNA (siRNA) targeting MK as a therapy for vein graft failure. METHODS: We first
      made a highly effective siRNA to rabbit MK. Jugular vein-to-carotid artery
      interposition vein grafts, which are applied to a low flow condition, were made
      in Japanese white rabbits. Small interfering RNA mixed with atelocollagen was
      administrated to the external wall of grafted veins. Cy3-conjugated stabilized
      siRNA was used to confirm its stability and successful transfer into the vein
      graft wall. Neointimal hyperplasia was evaluated 4 weeks after the operation. The
      proliferation index and leukocyte infiltration were determined. RESULTS: MK
      expression was induced and reached the maximum level 7 days after operation.
      Fluorescence of Cy3-labeled siRNA could be detected in the graft wall even 7 days
      after operation. Knockdown of the gradually increasing expression was achieved by
      perivascular application of siRNA using atelocollagen. The intima-media ratio and
      the intima thickness at 28 days after grafting were both reduced >90% by this
      treatment compared with controls. This phenomenon was preceded by significant
      reductions of inflammatory cell recruitment to the vessel walls and subsequent
      cell proliferation in MK siRNA-treated grafts. CONCLUSIONS: These results suggest
      that midkine is a candidate molecular target for preventing vein graft failure.
      Furthermore, for clinical applications of siRNA, a single intraoperative
      atelocollagen-based nonviral delivery method could be a reliable approach to
      achieve maximal function of siRNA in vivo. This strategy may be a useful and
      practical form of gene therapy against human vein graft failure.

PMID- 16950447
TI  - Combined open and endovascular treatment of a saccular aneurysm and redundant
      loop of the internal carotid artery.
AB  - We report the unusual case of a woman with a saccular aneurysm of the distal
      cervical internal carotid artery arising just distal to a kink and a 360 degrees
      redundant loop. The retromandibular position of the aneurysm would have mandated
      a complex surgical procedure. A purely endovascular approach was not possible
      owing to the difficulty to pass any kind of device beyond the redundant loop. A
      hybrid approach, in which the kink was surgically straightened and the saccular
      aneurysm coiled after stenting of its orifice, was therefore used to treat this
      challenging case. A review of the literature supporting this approach is
      discussed.

PMID- 16950448
TI  - Isolated celiac artery aneurysm with splenic artery stenosis as a rare
      presentation of polyarteritis nodosum: a case report and review of the
      literature.
AB  - Polyarteritis nodosum (PAN) is a vasculitic disease that affects small to medium
      arteries. It often presents as a systemic and multiorgan disease that affects the
      skin, joints, gastrointestinal tract, kidneys, and nervous system. Nonspecific
      signs and symptoms are the hallmarks of PAN. It rarely affects single vessels,
      although there have been case reports of PAN involving single intra-abdominal
      vessels. The authors present a case of a 42-year-old white man who presented with
      mild epigastric pain but was otherwise asymptomatic. The workup ultimately
      revealed a rare case of an isolated celiac artery aneurysm with a concomitant
      stenosis of the splenic artery secondary to PAN. The patient was treated with
      high-dose steroid therapy, with resultant resolution of the vasculitis and a
      decreased size of the aneurysm.

PMID- 16950449
TI  - Robot-assisted laparoscopic renal artery aneurysm reconstruction.
AB  - We report the surgical management of an expanding 2.5-cm left-sided renal artery
      aneurysm using a robotic-assisted laparoscopic approach. Using the da Vinci
      surgical robotic system, we resected the aneurysm, and the anterior-inferior
      branch of the renal artery was reconstructed with an end-to-end anastomosis. The
      operative time was 360 minutes, hospitalization length of stay was 3 days, and
      postoperative analgesic requirements were minimal. Follow-up imaging and
      functional analysis demonstrated resolution of the aneurysm and preservation of
      renal function. This technique highlights the ability of surgical robotics to
      expand indications for minimally invasive surgery in complex cases.

PMID- 16950450
TI  - Tuberculous pseudoaneurysm of the femoral artery complicated by cutaneous
      tuberculosis of the foot: a case report.
AB  - An infected pseudoaneurysm of the right common femoral artery in a 69-year-old
      patient receiving methotrexate therapy was confirmed to have been caused by
      Mycobacterium tuberculosis. After surgical excision of the aneurysm and
      revascularization using femoral vein, cutaneous manifestations of M tuberculosis
      infection in the foot complicated the course. We hypothesized that methotrexate
      may have triggered the reactivation of dormant tuberculosis in this patient.
      Because extrapulmonary tuberculous pseudoaneurysms are clinically similar to
      other types of infected pseudoaneurysm, M tuberculosis infection should always be
      suspected during the initial diagnosis. We propose that mycobacterial cultures
      should be routine when initial cultures and Gram stain are negative.

PMID- 16950451
TI  - Massive spouting bleeding from chronic stasis ulceration caused by arteriovenous
      communication of the lower extremity.
AB  - We report a case of massive bleeding from a varicose vein in a calf. A 56-year
      old man was brought into the emergency unit of our hospital with massive bleeding
      from an ulcer on his left calf. A duplex scan and arteriography revealed
      arteriovenous communication at the site of stasis ulceration. After primary
      hemostasis, coil embolization of the feeding artery to the arteriovenous
      communication was successfully performed, followed by stripping of the greater
      saphenous vein. Careful attention thus needs to be paid to arteriovenous
      communication that can cause life-threatening bleeding from stasis ulceration.
      Coil embolization of the feeding arterial branch can safely and effectively treat
      this disease.

PMID- 16950452
TI  - Aneurysm of the celiac artery arising from a celiomesenteric trunk.

PMID- 16950453
TI  - Patient selection for carotid stenting versus endarterectomy: a systematic
      review.
AB  - Carotid artery stenting has emerged as an alternative to carotid endarterectomy
      for the treatment of severe extracranial carotid stenosis in patients with
      anatomic or clinical factors that increase their risk of complications with
      surgery, yet there remains a substantial amount of variability and uncertainty in
      clinical practice in the referral of patients for stenting vs endarterectomy. By
      undertaking a thorough review of the literature, we sought to better define which
      subsets of patients with "high-risk" features would be likely to preferentially
      benefit from carotid stenting or carotid endarterectomy. Although only a single
      randomized trial comparing the outcomes of carotid stenting with distal
      protection and endarterectomy has been completed, a wealth of observational data
      was reviewed. Relative to endarterectomy, the results of carotid stenting seem
      favorable in the setting of several anatomic conditions that render surgery
      technically difficult, such as restenosis after prior endarterectomy, prior
      radical neck surgery, and previous radiation therapy involving the neck. The
      results of stenting are also favorable among patients with severe concomitant
      cardiac disease. Carotid endarterectomy, alternatively, seems to represent the
      procedure of choice among patients 80 years of age or older in the absence of
      other high-risk features. Overall, existing data support the concept that carotid
      stenting and endarterectomy represent complementary rather than competing modes
      of therapy. Pending the availability of randomized trial data to help guide
      procedural selection, which is likely many years away, an objective understanding
      of existing data is valuable to help select the optimal mode of revascularization
      therapy for patients with severe carotid artery disease who are at heightened
      surgical risk.

PMID- 16950455
TI  - My brother's keeper: uncompensated care for illegal immigrants.

PMID- 16950456
TI  - Attentional shifting and the role of the dorsal pathway in visual word
      recognition.
AB  - A substantial amount of evidence has been collected to propose an exclusive role
      for the dorsal visual pathway in the control of guided visual search mechanisms,
      specifically in the preattentive direction of spatial selection [Vidyasagar, T.
      R. (1999). A neuronal model of attentional spotlight: Parietal guiding the
      temporal. Brain Research and Reviews, 30, 66-76; Vidyasagar, T. R. (2001). From
      attentional gating in macaque primary visual cortex to dyslexia in humans.
      Progress in Brain Research, 134, 297-312]. Moreover, it has been suggested
      recently that the dorsal visual pathway is specifically involved in the spatial
      selection and sequencing required for orthographic processing in visual word
      recognition. In this experiment we manipulate the demands for spatial processing
      in a word recognition, lexical decision task by presenting target words in a
      normal spatial configuration, or where the constituent letters of each word are
      spatially shifted relative to each other. Accurate word recognition in the
      Shifted-words condition should demand higher spatial encoding requirements,
      thereby making greater demands on the dorsal visual stream.
      Magnetoencephalographic (MEG) neuroimaging revealed a high frequency (35-40Hz)
      right posterior parietal activation consistent with dorsal stream involvement
      occurring between 100 and 300ms post-stimulus onset, and then again at 200-400ms.
      Moreover, this signal was stronger in the shifted word condition, compared to the
      normal word condition. This result provides neurophysiological evidence that the
      dorsal visual stream may play an important role in visual word recognition and
      reading. These results further provide a plausible link between early stage
      theories of reading, and the magnocellular-deficit theory of dyslexia, which
      characterises many types of reading difficulty.

PMID- 16950457
TI  - Alterations in working memory as a function of leukoaraiosis in dementia.
AB  - Dementia research suggests executive dysfunction is best understood within the
      context of disease-specific neuropathology. Leukoaraiosis (LA) results in
      executive dysfunction yet little is known about its impact on specific aspects of
      working memory (WM). This study aimed to investigate the relationship between MRI
      LA severity and WM in dementia. A visual rating scale was used to assign patients
      with dementia into groups with minimal-mild LA (Low LA; n=34) and moderate-severe
      LA (High LA; n=32). A modified Digit Span Backward Task consisting of 3-, 4-, and
      5-span trials measured specific components of WM. Short-term storage and
      rehearsal in WM were assessed by the total number of digits reported regardless
      of recall order (ANY-ORDER; e.g., 47981 recalled '18943', score=4). Mental
      manipulation in the form of disengagement and temporal re-ordering was assessed
      by the total number of digits recalled in correct position (SERIAL-ORDER; e.g.,
      47981 recalled '18943', score=3). There was no difference between LA groups on
      ANY-ORDER comparisons. The High LA group obtained lower SERIAL-ORDER scores than
      the Low LA group. Stepwise regression analyses were conducted that first entered
      MMSE scores then composite z-scores reflecting executive functioning, language
      and memory. ANY-ORDER performance variance was explained solely by dementia
      severity. SERIAL-ORDER performance variance was further explained by executive
      dysfunction. Results suggest that high degrees of LA do not interfere with
      immediate (digit) recall but do interfere with disengagement and temporal re
      ordering. LA may disconnect the frontal lobes from subcortical and cortical
      structures that form the neuronal networks critical for these WM functions.

PMID- 16950458
TI  - Contributions of undernutrition and handling to huddling development of rats.
AB  - When newborn rats are separated from the mother, they consistently exhibit the
      huddling response to maintain body temperature and physical contact. Therefore,
      we investigated if preweaning handling/sensory stimulation may overcome the
      huddling deficiencies associated to neonatal undernourishment/maternal
      deprivation of Wistar rats maintained at constant temperature (30 degrees C). The
      data indicated that initial and final temperatures in the pile of undernourished
      (U) and undernourished stimulated (Us) pups was reduced compared to their
      controls (C and Cs, respectively). Huddling latency was prolonged at 5 days of
      age in the Us group and at 20 days of age in the U pups. On postpartum day 5, U
      and Us subjects were similar in battery and pile-huddling performance compared to
      their controls; thereafter, the frequency of battery type was low and pile type
      was high (in frequency) in all experimental treatments. The frequency of
      recycling from the pile in the Us pups in most of the ages was significantly
      reduced compared to U and C subjects, suggesting that early sensory stimulation
      possibly accelerates the maturation of thermoregulatory brain structures
      underlying the huddling response and causing increased physical contacts. The
      data provide evidence that both neonatal undernutrition/maternal deprivation and
      early sensory stimulation may modify the huddling response by reducing or
      increasing, respectively, brain mechanisms underlying huddling. The amount of
      physical contact the newborns receive from their littermates and the mother may
      be a fundamental source of sensory cues for neuronal maturation and brain
      functioning.

PMID- 16950461
TI  - Age-related changes in left ventricular twist assessed by two-dimensional speckle
      tracking imaging.
AB  - The aim of this study was to determine the normal value of left ventricular (LV)
      twist, and to examine the effects of aging on LV twist by newly developed 2
      dimensional ultrasound speckle-tracking imaging. We acquired basal and apical LV
      short-axis second harmonic images in 118 healthy volunteers. Using commercially
      available 2-dimensional strain software, time-domain speckle tracking was
      performed, and mean value of LV rotation obtained at each plane. LV twist was
      defined as apical rotation relative to the base. Adequate data were obtained in
      113 volunteers. During systole, the LV performs a wringing motion with a
      counterclockwise rotation at the apex and a clockwise rotation at the base. The
      mean value of peak twist was 7.7 +/- 3.5 degrees. Immediately after end systole,
      rapid untwisting develops. Different LV twist profiles are noted according to
      age. Peak LV twist was significantly higher, and the rate of LV untwisting
      significantly reduced and delayed, with advancing age. LV twist can be measured
      noninvasively by 2-dimensional ultrasound speckle-tracking imaging. The observed
      reduced and delayed diastolic untwisting with aging may contribute toward the
      tendency of diastolic dysfunction. This novel method allows the detailed study of
      diastolic function in various cardiovascular diseases.

PMID- 16950462
TI  - Left ventricular systolic longitudinal function: comparison among simple M-mode,
      pulsed, and M-mode color tissue Doppler of mitral annulus in healthy individuals.
AB  - BACKGROUND: M-mode determination of left ventricular (LV) atrioventricular plane
      displacement (AVPD) allows a simple assessment of LV longitudinal systolic
      function. Color tissue Doppler (TD) M-mode-derived AVPD and pulsed TD-derived
      systolic annular velocity are more sophisticated tools. OBJECTIVE: We sought to
      compare these 3 techniques for the analysis of LV longitudinal systolic function.
      METHODS: Standard M-mode AVPD, color TD M-mode AVPD, and systolic annular
      velocity were measured at 4 annular levels in 56 healthy individuals. The time to
      onset and the electromechanical interval were also determined using each
      technique. RESULTS: Standard M-mode AVPD (r = 0.56, P < .0001) and color TD M
      mode AVPD (r = .65, P < .0001) showed good correlation with systolic annular
      velocity. All 3 techniques revealed an inhomogeneous systolic shifting among
      different annular portions. Systolic intervals showed small discrepancies but
      high concordance between M-mode techniques and pulsed TD. CONCLUSIONS: Standard M
      mode imaging of the mitral annulus may be considered a reliable method for the
      assessment of LV longitudinal function.

PMID- 16950463
TI  - Analysis of mitral annulus motion measurements derived from M-mode, anatomic M
      mode, tissue Doppler displacement, and 2-dimensional strain imaging.
AB  - BACKGROUND: Left ventricular longitudinal shortening plays an important role in
      cardiac contraction and can be measured by the mitral annulus motion (MAM) toward
      the cardiac apex. MAM can be evaluated by conventional M-mode, anatomic M-mode
      (AM-mode), tissue Doppler displacement (TDD), and 2-dimensional strain imaging
      (2DSI). OBJECTIVE: The aim of the study was to compare these 4 different methods
      for measuring MAM. METHODS: MAM was evaluated in 25 patients by M-mode, AM-mode,
      TDD, and 2DSI. Two walls (septal and lateral) in apical 4-chamber view were
      analyzed. RESULTS: The angle correction between M-mode and AM-mode was
      significantly higher in the lateral wall (septum 2.2 +/- 1.6 vs lateral 4.1 +/-
      1.6 degrees, P < 0.01). However, with angle correction up to 8 degrees, the
      measurements obtained were not significantly different from those obtained by M
      mode. No significant differences were found among 2DSI, M-mode, and AM-mode
      either, although all of them were significantly higher in comparison with TDD
      measurements in both septal (M-mode [11.0 +/- 2.4 mm], AM-mode [11.8 +/- 2.4 mm],
      2DSI [11.0 +/- 3.4 mm] vs TDD [9.2 +/- 3.3 mm], P < .01) and lateral (M-mode
      [11.9 +/- 2.3 mm], AM-mode [12.4 +/- 2.8 mm], 2DSI [10.4 +/- 3.9 mm] vs TDD [8.9
      +/- 3.0 mm], P < .05) walls. The +/- 2SD variation from the mean difference in
      septal and lateral walls were, respectively, between: M-mode and TDD, -2.4 to 5.9
      and -2.2 to 8.2 mm; M-mode and 2DSI, -5.7 to 5.7 and -5.8 to 8.7; AM-mode and
      TDD, -2.5 to 5.6 and -2.7 to 9.6; AM-mode and 2DSI, -5.7 to 5.87 and -5.9 to 9.8
      and TDD and 2DSI, -3.2 to 6.6 and -5.3 to 8.4. CONCLUSIONS: AM-mode and M-mode
      measurements did not differ significantly. Despite the good correlation among all
      methods they were not interchangeable. TDD measurements were significantly lower
      than M-mode, AM-mode, and 2DSI measurements. M-mode and AM-mode are angle
      dependent and can, therefore, underestimate or overestimate MAM. The new method
      of 2DSI is promising because it tracks natural acoustic markers and is not angle
      dependent and, therefore, measures the true local tissue motion.

PMID- 16950464
TI  - Analysis of postsystolic myocardial thickening work in selective myocardial
      layers during progressive myocardial ischemia.
AB  - BACKGROUND: Myocardial function is transmurally heterogeneous. Postsystolic work
      may functionally reflect ischemic but viable myocardium. We calculated systolic
      and postsystolic regional myocardial work index (RMWi) in subendocardial and
      subepicardial layers of myocardium supplied by a slowly occluding coronary
      artery. METHODS: Progressive stenosis of the left anterior descending coronary
      artery lasting 11 +/- 5 days (end point) was induced in 10 dogs, and pressure
      strain loops were obtained from subendocardial and subepicardial layers of apical
      and middle anterior segments by intracardiac ultrasound. RESULTS: At baseline,
      the RMWi was significantly higher (P < .05) in the subendocardial layer. At the
      end point, there was no significant change in the RMWi in ischemic myocardium;
      however, the postsystolic RMWi was higher (P < .05) in the subendocardial layer
      and accompanied a decrease in subendocardial myocardial blood flow, although
      viability was largely maintained. CONCLUSION: A significant subendocardial
      postsystolic RMWi at rest suggests an impending ischemic injury in coronary
      artery disease when segmental function is still preserved.

PMID- 16950465
TI  - Intraventricular pressure gradients in left ventricular aneurysms determined by
      color M-mode Doppler method: an animal study.
AB  - BACKGROUND: Left ventricular aneurysm (LVA) may affect diastolic intraventricular
      blood flow. Color M-mode (CMM) Doppler flow propagation patterns are abnormal in
      the presence of apical aneurysms. The aim of this study was to validate the
      accuracy of CMM echocardiography for assessing the existence and size of LVA and
      to determine the intraventricular pressure gradient in LVA. METHODS: CMM of the
      transmitral inflow in early diastole was obtained from the apical 4-chamber view
      in 19 sheep. The presence of the break point where the velocity decreased
      abruptly in the mitral inflow (point D) was determined and the distance between
      the apex and point D was measured. The intraventricular pressure difference
      between the base and the apex was measured by a catheter while it was calculated
      using CMM with the Euler equation. RESULTS: The presence of the break point D
      showed 84% sensitivity and 100% specificity for determining the existence of an
      LVA. Distance between the apex and point D correlated well with scar size.
      Catheter- and CMM-derived intraventricular pressure difference correlated and
      agreed well (y = 1.0 x -0.2, r = 0.94). CONCLUSIONS: The point of abrupt decrease
      in propagation velocity of the CMM recording indicated the presence and size of
      LVA. Intraventricular pressure gradients were determined noninvasively by CMM
      echocardiography with reasonable accuracy.

PMID- 16950466
TI  - Accuracy and feasibility of online 3-dimensional echocardiography for measurement
      of left ventricular parameters.
AB  - BACKGROUND: The availability of automated online software may increase the
      feasibility of real-time 3-dimensional (3D) echocardiography (3DE) for left
      ventricular (LV) volume calculation in clinical practice. We sought to compare
      offline and online approaches with magnetic resonance imaging (MRI). METHODS:
      Patients who presented to the clinical laboratory for evaluation of LV parameters
      (n = 110, 94 men, age 63 +/- 10 years) were studied with 2-dimensional
      echocardiography, online and offline 3DE, and MRI. The 3DE measurements were
      obtained by a semiautomated LV border detection based on tracing (online) and
      edge detection (offline). MRI images were obtained using true free induction
      steady-state precession during breath hold, with measurement of 3D volumes and
      ejection fraction (EF). RESULTS: All echocardiographic techniques underestimated
      LV volumes, but EF estimations were similar. The best correlation was between MRI
      versus offline 3DE. The correlation of online 3DE with MRI was significantly
      better than 2-dimensional echocardiography (end-diastolic volume (EDV) z = 4.2,
      end-systolic volume (ESV) z = 4.44, EF z = 4.32; all P < .01). However,
      correlation of offline 3DE with MRI was significantly better than online 3DE (EDV
      z = 2.57, P < .05; ESV z = 2.42, P < .05; EF z = 3.82, P < .01). Images were
      considered to be good quality (endocardium visualized in all walls) in 49
      patients; discrepancies between online and offline 3DE and MRI were similar in
      good- and poor-quality images. Wall-motion abnormalities were present in 98
      patients; discrepancies with MRI were similar in patients with and without
      abnormal wall motion. CONCLUSIONS: Online measurement of LV volumes is feasible
      and more accurate than with 2-dimensional echocardiography. Although the offline
      approach is more accurate, it is also more time-consuming.

PMID- 16950467
TI  - Asymmetry of systolic anterior motion of the mitral valve in patients with
      hypertrophic obstructive cardiomyopathy: a real-time three-dimensional
      echocardiographic study.
AB  - By geometric analysis of real-time 3-dimensional echocardiography performed in 39
      patients with hypertrophic obstructive cardiomyopathy and definite systolic
      anterior motion of the mitral valve, we found that the angle between the mitral
      annular plane and basal portion of the anterior mitral valve leaflet, and the
      angle between the basal portion of the anterior leaflet and its tip portion
      measured in the medial and central anteroposterior planes, were significantly
      smaller than those in the lateral plane. The distance between the
      interventricular septum and the anterior mitral valve tip in the medial and
      central plane was also significantly smaller than that in the lateral plane. The
      lateral distance between the interventricular septum and the anterior mitral
      valve tip was the only independent determinant of left ventricular outflow tract
      pressure gradient by multiple stepwise regression analysis. In conclusion,
      systolic anterior motion of the mitral valve develops predominantly in the medial
      side, resulting in laterally located narrow left ventricular outflow tract
      opening in patients with hypertrophic obstructive cardiomyopathy.

PMID- 16950468
TI  - Role of biplane and biplane echocardiographically guided 3-dimensional
      echocardiography during dobutamine stress echocardiography.
AB  - Image acquisition time and wall-motion score of conventional 2-dimensional (2D)
      dobutamine stress echocardiography (DSE) were compared with those of biplane and
      3-dimensional (3D) DSE in 50 patients (age 67 +/- 13 years) with regular rhythms
      during clinically indicated DSE. Commercially available systems were used for the
      study. We used a conventional transducer for 2D and a matrix-array transducer (x4
      or x3-1) for two biplane (60- and 120-degree) images and one 3D full-volume
      image. Image quality was scored as 1 = good; 2 = adequate; and 3 = inadequate.
      Segmental wall-motion scores for each method were analyzed in blinded fashion.
      Acquisition times of biplane (9.3 +/- 2.8 seconds) and biplane-guided 3D
      (additional 2.6 +/- 1.0 seconds) echocardiography were significantly shorter than
      those of conventional 2D DSE (60.0 +/- 26.7 seconds) (P < .001). Image quality
      was adequate or good in 94% for biplane and 96% for 3D echocardiography.
      Agreement of segmental wall-motion score was present in 87.6% of segments for 2D
      versus biplane and 85.9% for 2D versus 3D at baseline and in 88.0% for 2D versus
      biplane and 87.4% for 2D versus 3D at peak stress. Acquisition of biplane or
      biplane-guided 3D volumetric data during DSE with use of a new matrix-array
      transducer was feasible and shortened image acquisition time without affecting
      the diagnostic yield compared with conventional 2D imaging.

PMID- 16950469
TI  - Hypotension during dobutamine stress transesophageal echocardiography:
      relationship with provoked left ventricular obstruction.
AB  - BACKGROUND: The mechanism of hypotension during dobutamine stress (DS)
      echocardiography is unknown. The role of left ventricular outflow tract (OT) or
      midcavitary (MID) obstruction provoked during stress in this process remains
      controversial. We hypothesized that left ventricular OT obstruction would account
      for hypotension as opposed to MID obstruction. METHODS: Multiplane DS
      transesophageal echocardiography (TEE) was performed in 142 adult patients who
      displayed no resting obstruction or DS-provoked ischemia. TEE was used to
      identify the precise site of obstruction. Dobutamine was infused from 5 to 40
      microg/kg/min and atropine as needed. Continuous wave Doppler was performed from
      appropriate views to assess for obstruction. RESULTS: Ventricular obstruction was
      provoked at the OT in 13 patients, MID in 10 patients, and at both sites in 4
      patients. A total of 115 patients without dobutamine-induced obstruction served
      as control subjects. Systolic blood pressure at rest was similar in all groups,
      but decreased to a greater magnitude from rest to peak stress in the OT (-20 +/-
      40 mm Hg) and MID (-29 +/- 38 mm Hg) groups as compared with the control group (8
      +/- 30 mm Hg). A hypotensive response (ie, decrease in systolic blood pressure >
      or = 20 mm Hg from baseline to peak stress) was significantly greater in OT (69%,
      P = .001) and MID (60%, P < .05) groups as compared with the control group (19%).
      Heart rate and ejection fraction at rest or peak did not differ among groups.
      Among clinical and hemodynamic variables, left ventricular OT (relative risk 5.9;
      95% confidence interval 1.9-18; P < .002) and MID (relative risk 3.6; 95%
      confidence interval 1.1-12; P < .05) obstructions were the only predictors for a
      hypotensive response. CONCLUSIONS: Hypotension during DS TEE occurs commonly when
      ventricular obstruction is provoked. These data support a causal relationship
      between a provoked ventricular obstruction and hypotension during DS TEE.

PMID- 16950470
TI  - Improved papillary muscle function attenuates functional mitral regurgitation in
      patients with dilated cardiomyopathy after cardiac resynchronization therapy.
AB  - BACKGROUND: Functional mitral valve regurgitation attenuation after cardiac
      resynchronization therapy (CRT) in patients with severe heart failure has been
      attributed to both the increased rate of left ventricular systolic pressure
      increase and to papillary muscle (PM) recoordinated contraction. We hypothesized
      that an increase in systolic deformation of the PMs or the adjacent myocardial
      wall may in part account for this effect, by preventing their outward
      displacement during systole. METHODS: We studied by echocardiography 22 patients
      with moderate/severe functional mitral valve regurgitation and a mean ejection
      fraction of 18 +/- 4% at baseline and after implantation of a CRT system.
      RESULTS: CRT induced a significant reduction of the effective regurgitant orifice
      area (0.18 +/- 0.11 vs 0.35 +/- 0.17 mm2, P < .001). Strain improved in both PMs
      and their adjacent walls, although this improvement was significant only in
      anterolateral PM (-16 +/- 4.7 vs -11 +/- 4.3%, P = .02) and posteromedial PM
      adjacent wall (-16 +/- 10 vs -8 +/- 4.6%, P = .01). CONCLUSIONS: CRT acutely
      reduces the severity of functional mitral valve regurgitation in patients with
      heart failure and this effect may be in part attributed to improved strain of PM
      or adjacent wall.

PMID- 16950471
TI  - Intraoperative assessment of mitral regurgitation: role of phenylephrine
      challenge.
AB  - OBJECTIVES: We defined the effects of the operative (OP) state and phenylephrine
      challenge on the assessment of mitral regurgitation (MR) severity. METHODS: In
      all, 57 patients underwent transesophageal echocardiographic assessment of MR
      severity pre-OP (PREOP) and intra-OP. MR severity was assessed PREOP under
      conscious sedation and intra-OP with general anesthesia, before and after
      hemodynamic manipulation with vasoactive agents, to match intra-OP and PREOP
      transesophageal echocardiographic mean arterial blood pressures. RESULTS: Intra
      OP MR and mean arterial pressure were less than PREOP in 27 patients (both P <
      .001). When PREOP and OP blood pressures were matched using phenylephrine, there
      was no significant difference in MR severity between the two states (P = 1.0).
      Nonetheless, MR severity was still underestimated in 6 patients and overestimated
      in 7 patients intra-OP. CONCLUSIONS: Intra-OP transesophageal echocardiography
      underestimates MR severity. Phenylephrine reduces, yet does not eliminate, intra
      OP underestimation of MR severity.

PMID- 16950472
TI  - Single-vessel versus multivessel territory acute ischemic stroke: value of
      transesophageal echocardiography in the differentiation of embolic stroke.
AB  - OBJECTIVES: We sought to assess the presence of potential aortic or cardiac
      sources of embolism in patients presenting with acute ischemic stroke in one or
      more vascular territories. BACKGROUND: In patients with acute ischemic stroke,
      involvement of multiple vascular territories has been used to implicate a cardiac
      or aortic source of embolus. It remains unclear whether patients with multivessel
      stroke have a higher frequency of cardiac or aortic embolic sources on
      transesophageal echocardiography (TEE) compared with patients with single
      territory stroke. METHODS: We identified 210 patients with acute ischemic stroke
      documented by neuroimaging undergoing TEE for identification of a potential
      embolic source. Patients were divided into 3 groups (lacunar stroke, nonlacunar
      stroke/single-vessel involvement, nonlacunar stroke/multivessel involvement) and
      the frequency of potential embolic sources on TEE was compared. RESULTS: Of the
      210 patients, 121 (58%) were male and the mean age was 61 years. In all, 139
      patients (66%) were classified as having single-vessel stroke, 47 (22%) as having
      multivessel stroke, and 24 (11%) as having lacunar stroke. On TEE, 87 patients
      (41%) had at least one potential source of embolism. Patients with multivessel
      strokes had fewer potential embolic sources on TEE than patients with single
      vessel or lacunar strokes (26% vs 46% and 46%, respectively; P = .043).
      CONCLUSIONS: In patients with acute ischemic stroke, the incidence of a potential
      cardiac or aortic source of embolism is high, regardless of the vascular
      distribution of the stroke. TEE may be a useful tool to assess the source of
      stroke in single-vessel, multivessel, and lacunar territory stroke distribution.
      We aimed to assess the presence of potential aortic or cardiac sources of
      embolism in patients presenting with acute ischemic stroke in one or more
      vascular territories. A total of 210 patients with acute ischemic stroke were
      divided into 3 groups (lacunar stroke, nonlacunar stroke/single-vessel
      involvement, nonlacunar stroke/multivessel involvement) and the frequency of
      potential embolic sources on transesophageal echocardiography was compared.
      Patients with multivessel strokes had fewer potential embolic sources on
      transesophageal echocardiography than patients with single-vessel or lacunar
      strokes, but the frequency of a potential cardiac or aortic source of embolism
      was high, regardless of the vascular distribution of stroke.

PMID- 16950473
TI  - Use of carotid intima-media thickness and vascular age to modify cardiovascular
      risk prediction.
AB  - BACKGROUND: This study identified predictors of patients for whom carotid artery
      intima-media thickness (CIMT) measurement and determination of vascular age could
      change cardiovascular disease (CVD) risk assessment. METHODS: We studied
      consecutive patients who were asymptomatic and nondiabetic, referred for
      ultrasound measurement of CIMT. Individuals with CIMT 75th percentile or greater
      for age, sex, and race were defined as having advanced subclinical
      atherosclerosis. CIMT values were converted to vascular age estimates and were
      used to modify Framingham 10-year CVD risk estimates. RESULTS: Of 506 patients,
      261 (51.6%) were not taking lipid-lowering therapy. Advanced subclinical
      atherosclerosis was present in 77 (30%). There were 62 patients (23.8%) with a
      change in CVD risk of 5% or more. Predictors of 5% or more change in CVD risk
      were systolic blood pressure (P < .001), total/high-density lipoprotein
      cholesterol ratio (P < .001), and male sex (P < .001). Of the 97 patients at
      moderate or moderately high risk, 56.7% changed risk classification. CONCLUSIONS:
      Measurement of CIMT and determination of vascular age can identify individuals
      with advanced subclinical atherosclerosis, resulting in clinically meaningful
      alterations in CVD risk estimates.

PMID- 16950474
TI  - Double atrial septum with persistent interatrial space: echocardiographic
      features of a rare atrial septal malformation.
AB  - We describe the echocardiographic features of 4 new cases of a rare atrial septal
      malformation consisting a double atrial septum with a midline chamber between the
      left and right atrium. Half of the cases had major left-sided obstructive
      lesions. Transthoracic, transesophageal, intracardiac, and fetal
      echocardiographic features of this anomaly are demonstrated. Previous
      descriptions, embryologic speculations, and clinical considerations are
      discussed.

PMID- 16950475
TI  - Atrial septal defect: anatomoechocardiographic correlation.
AB  - This study was undertaken to enhance understanding of the anatomic abnormalities
      involved in atrial septal defect (ASD) based on the anatomoechocardiographic
      comparison of equivalent specimens of ASD and the echocardiograms of patients
      with this anomaly. Of the 72 heart specimens, two had common atrioventricular
      canal (2.8%) and one had absence of right atrioventricular connection (1.4%). In
      all, 46 (63.8%) had fossa ovalis type ASD, two (2.8%) had true ostium secundum
      type ASD, two (2.8%) had ostium primum type ASD, two (2.8%) had superior sinus
      venosus type ASD, and two (2.8%) had inferior sinus venosus type ASD. One (1.4%)
      specimen had a coronary venous sinus type ASD and 14 (19.4%) had mixed type ASD.
      Of the 144 patients evaluated with echocardiography 15 (10.4%) had common
      atrioventricular canal, one (0.7%) had right absence of atrioventricular
      connection, 105 (72.9%) had ostium secundum type ASD (fossa ovalis), 10 (7%) had
      mixed type ASD, 9 (6.2%) had superior venous sinus type ASD, two (1.4%) had
      ostium primum type ASD, and two (1.4%) had true fossa ovalis type ASD. This
      series leads us to conclude that the key to successful management of ASD depends
      on understanding echocardiographic images in terms of anatomic specimens to
      provide appropriate evaluations for therapeutic decisions and establishment of
      prognoses.

PMID- 16950476
TI  - Can transthoracic live 3-dimensional echocardiography improve the recognition of
      midventricular obliteration in hypertrophic obstructive cardiomyopathy?
AB  - In this report the authors analyzed the usefulness of live 3-dimensional
      echocardiography in association with conventional 2-dimensional method to improve
      the recognition of left ventricular midcavitary obliteration in a patient with
      hypertrophic cardiomyopathy.

PMID- 16950477
TI  - Heart failure and severe pulmonary hypertension caused by distal detachment of
      the valve conduit 16 years after the Cabrol composite graft procedure.
AB  - We report the case of a patient who underwent Cabrol composite graft procedure
      for ascending aorta aneurysm and aortic regurgitation. Sixteen years later he
      developed progressive dyspnea and a left-to-right shunt caused by distal
      detachment of the valve conduit with persistence of the perigraft space-right
      atrial fistula visualized with echocardiography. Our case shows that late
      manifestations of surgical complications of the Cabrol procedure may occur and
      transesophageal echocardiography may allow a comprehensive assessment in these
      patients. However, because surgical management of ascending aorta aneurysms has
      changed in the last decades a detailed knowledge of the surgical technique used
      is mandatory for adequate interpretation of transesophageal echocardiographic
      results.

PMID- 16950478
TI  - Takotsubo cardiomyopathy: a case report.
AB  - We present the case of a 49-year-old Caucasian woman exhibiting symptoms of an
      acute coronary syndrome while hospitalized for alcohol withdrawal.
      Echocardiography demonstrated an unusual pattern of left ventricular dysfunction
      in which all segments except the base become akinetic, known as takotsubo
      cardiomyopathy.

PMID- 16950479
TI  - Continuous wave Doppler signal: a mystery.
AB  - Doppler echocardiography is an established noninvasive cardiovascular
      investigational tool. However, the physical nature of the ultrasound beam may
      lead to unexpected findings in routine echocardiographic examination, which may
      lead to misdiagnosis and subsequent wrong clinical decisions.

PMID- 16950480
TI  - Pulmonary artery dissection: a rare complication of pulmonary balloon
      valvuloplasty diagnosed 11 years after the procedure.

PMID- 16950481
TI  - Right coronary cameral fistula resulting from surgery of double chamber right
      ventricle.

PMID- 16950482
TI  - Intracardiac echocardiography: evolution, recent advances, and current
      applications.

PMID- 16950483
TI  - Two biflavonoids from Ouratea nigroviolacea.
AB  - The leaves of Ouratea nigroviolacea (Ochnaceae) afforded two biflavonoids,
      ouratine A and B together with agathisflavone and stigmasterol. The biflavonoids
      were characterized as 4'-O-methylated apigeninyl-(I-6, II-8)-4'-O
      methylatedapigenin and 4'-O-methylated apigeninyl-(I-6, II-8) apigenin by
      spectral and chemical transformation studies.

PMID- 16950484
TI  - The rolC gene induces expression of a pathogenesis-related beta-1,3-glucanase in
      transformed ginseng cells.
AB  - The Agrobacterium rhizogenes rolC oncogene is capable of stimulating production
      of secondary metabolites in transformed plant cells that suggest its possible
      involvement in plant defense reactions. We tested whether the gene could also
      affect production of pathogenesis-related proteins. Using a well-known group of
      PR-proteins, such as beta-1,3-glucanases, we observed a 10-fold increase in total
      beta-1,3-glucanase activity in rolC-transformed Panax ginseng cells compared with
      normal cells. The increase was due to the production of a salicylic acid
      activated beta-1,3-glucanase isoform. We isolated cDNA of the corresponding beta
      1,3-glucanase gene (Pg-glu1), which shared 38-60% sequence identity with
      previously reported sequences of plant beta-1,3-glucanases at the protein level.
      Levels of Pg-glu1 mRNA transcripts were tightly correlated with expression of the
      rolC gene. Our data, together with previously reported information, indicate that
      A. rhizogenes can activate plant defense reactions via expression of T-DNA
      oncogenes.

PMID- 16950485
TI  - Triterpenoid saponins from Pteleopsis suberosa stem bark.
AB  - Thirteen oleanane saponins (1-13), four of which were new compounds (1-4), were
      isolated from Pteleopsis suberosa Engl. et Diels stem bark (Combretaceae). Their
      structures were determined by 1D and 2D NMR spectroscopy and ESI-MS spectrometry.
      The compounds were identified as 2alpha,3beta,19alpha,23,24-pentahydroxy-11-oxo
      olean-12-en-28-oic acid 28-O-beta-D-glucopyranosyl ester (1),
      2alpha,3beta,19beta,23,24-pentahydroxy-11-oxo-olean-12-en-28-oic acid 28-O-beta-D
      glucopyranosyl ester (2), 2alpha,3beta,19alpha,23-tetrahydroxy-11-oxo-olean-12-en
      28-oic acid 28-O-beta-D-glucopyranosyl ester (3), and
      2alpha,3beta,6beta,19alpha,24-pentahydroxy-11-oxo-olean-12- en-28-oic acid 28-O
      beta-D-glucopyranosyl ester (4). The presence of alpha,beta-unsaturated carbonyl
      function was not common in the oleanane class and the aglycons of these compounds
      were not found previously in the literature. Moreover, the isolated compounds
      were tested against Helicobacter pylori standard and vacA, and cagA clinical
      virulence genotypes. Results showed that compound 6 has an anti-H. pylori
      activity against three metronidazole-resistant strains (Ci 1 cagA, Ci 2 vacA, and
      Ci 3).

PMID- 16950486
TI  - Fluoroquinolone resistance in Salmonella typhi and S. paratyphi A in Bangalore,
      India.
AB  - Fluoroquinolone resistance in Salmonella typhi and S. paratyphi A is being
      increasingly reported. The minimum inhibitory concentrations (MICs) of
      ciprofloxacin, ofloxacin, levofloxacin and gatifloxacin against S. typhi and S.
      paratyphi A were compared. Fifty blood culture isolates, 25 S. typhi and 25 S.
      paratyphi A, were studied. The MICs were determined by the agar dilution method.
      Disc diffusion was done for the fluoroquinolones and other antibiotics. Nalidixic
      acid resistance was seen in 21/25 S. paratyphi A and 17/25 S. typhi isolates, and
      these had higher MICs to fluoroquinolones. Five S. typhi and six S. paratyphi A
      were fully resistant to ciprofloxacin (MIC >2 microg/l). No multidrug resistance
      was seen in S. typhi. The absence of multidrug resistance and presence of
      fluoroquinolone resistance warrants a review of therapy for enteric fever.

PMID- 16950487
TI  - Malaria treatment-seeking behaviour and drug prescription practices in an area of
      low transmission in Uganda: implications for prevention and control.
AB  - Knowledge of malaria and treatment-seeking behaviour was investigated in an area
      of low transmission in Uganda to help health services to plan for appropriate
      interventions to control malaria. Although knowledge of malaria symptoms,
      preventive methods and malaria risks was widespread, few were actually using
      insecticide-treated nets. Many patients (25%) had received treatment prior to
      visiting a health facility, with drug shops and general stores being the main
      sources of treatment. Some shops dispensed quinine, a second-line drug
      recommended for complicated malaria. Prescription practices of health staff often
      did not comply with guidelines. Only 30% of patients received treatment at a
      health facility within 24h of onset of symptoms. Findings indicate a need for
      community-level information campaigns on prompt treatment and introduction of
      home-based management of fever. Measures are needed to protect second-line drugs
      from misuse. Failure to comply with drug policy in both the private and public
      sectors is of concern in an era of rapidly evolving drug policy changes and
      highlights the need for reorientation and training of health staff and drug
      vendors to improve malaria diagnostic and treatment skills.

PMID- 16950488
TI  - Years of potential life lost in residents affected by floods in Hunan, China.
AB  - The potential life loss caused by floods has not been studied before. We carried
      out a retrospective cohort study in flood areas in Hunan, China in 1999. The
      standard mortality rate (SMR) and years of potential life lost (YPLL) were used
      to quantify the burden of flood on health. The SMRs of injury/poisoning and
      malignant neoplasm were higher in the river flood (151.36 x 10(-5), 127.30 x 10(
      5)) and drainage problems (143.74 x 10(-5), 105.87 x 10(-5)) groups than those in
      the no-flood group (113.40 x 10(-5), 74.81 x 10(-5)). The standard rates of YPLL
      (SYPLL per thousand) in the river flood (89.56 per thousand) and drainage
      problems (71.30 per thousand) groups were significantly higher than those in the
      no-flood group (65.74 per thousand, P<0.05). The SYPLL was significantly higher
      in males than in females. The percentages of attributable risk (PARs) of SMRs and
      PARs of SYPLLs resulting from flood were 12.26 and 26.60% in the river flood
      group and 10.56 and 7.80% in the drainage problems group. We conclude that floods
      increase the affected residents' SYPLL, and that the river flood had stronger
      effects than the drainage problems floods.

PMID- 16950489
TI  - The effect of the Holling type II functional response on apparent competition.
AB  - This article analyzes the classical 2-resource-1-consumer apparent competition
      community module with the Holling type II functional response. Two types of
      resource regulation (top-down vs. combined top-down and bottom-up) and two types
      of consumer behaviors (inflexible consumers with fixed preferences for resources
      vs. adaptive consumers) are considered. When resources grow exponentially and
      consumers are inflexible foragers, one resource is always outcompeted due to
      strong apparent competition. Density dependent resource growth relaxes apparent
      competition so that resources can coexist. As multiple attractors (either
      equilibria or limit cycles) coexist, population dynamics and community
      composition depend on initial population densities. Population dynamics change
      dramatically when consumers forage adaptively. In this case, the results both for
      top-down, and combined top-down and bottom-up regulation are similar and they
      show that species persistence occurs for a much larger set of parameter values
      when compared with inflexible consumers. Moreover, population dynamics will be
      chaotic when resource carrying capacities are high enough. This shows that
      adaptive consumer switching can destabilize population dynamics.

PMID- 16950490
TI  - An ultrasonic array sensor for spacecraft leak direction finding.
AB  - We have developed an ultrasonic array sensor useable for locating air leaks in
      manned spacecraft and have found that this sensor locates leaks in a 1-m(2) plate
      to within 2 cm. The sensor consists of a 63-element multiplexed array plus a
      reference element, all constructed from a single PZT disc and a printed circuit
      board. Cross-correlations of signals from the array elements with signals from
      the single reference element provide a measurement of the leak noise passing
      through the spacecraft skin under the array. A spatial Fourier transform reveals
      the dominant direction of propagation. Triangulation from multiple sensor
      locations can be used to find the source of the leak.

PMID- 16950491
TI  - Role of Bcl-2 expression for productive herpes simplex virus 2 replication.
AB  - Herpes simplex viruses infect a variety of cells in vitro. However, not all
      infected cells sustain a fully productive replication of these viruses. We have
      shown that, in U937 monocytoid cells, herpes simplex virus 2 (HSV-2) causes a low
      productive infection characterized by apoptosis as cytopathic effect at a late
      stage of infection. This effect was associated with a down-regulation of the Bcl
      2 protein. We therefore asked whether destabilization of Bcl-2 expression could
      act as a limiting factor for the productive HSV-2 infection. We found that
      overexpression of Bcl-2 in U937 cells dramatically increased the capability of
      these cells to sustain a fully productive infection, while protecting against
      apoptosis induced by HSV-2. Overall, our data indicate that Bcl-2 expression acts
      as a regulator of HSV-2 replication.

PMID- 16950492
TI  - RNA-binding properties and membrane insertion of Melon necrotic spot virus (MNSV)
      double gene block movement proteins.
AB  - Advances in structural and biochemical properties of carmovirus movement proteins
      (MPs) have only been obtained in p7 and p9 from Carnation mottle virus (CarMV).
      Alignment of carmovirus MPs revealed a low conservation of amino acid identity
      but interestingly, similarity was elevated in regions associated with the
      functional secondary structure elements reported for CarMV which were conserved
      in all studied proteins. Nevertheless, some differential features in relation
      with CarMV MPs were identified in those from Melon necrotic virus (MNSV) (p7A and
      p7B). p7A was a soluble non-sequence specific RNA-binding protein, but unlike
      CarMV p7, its central region alone could not account for the RNA-binding
      properties of the entire protein. In fact, a 22-amino acid synthetic peptide
      whose sequence corresponds to this central region rendered an apparent
      dissociation constant (K(d)) significantly higher than that of the corresponding
      entire protein (9 mM vs. 0.83-25.7 microM). This p7A-derived peptide could be
      induced to fold into an alpha-helical structure as demonstrated for other
      carmovirus p7-like proteins. Additionally, in vitro fractionation of p7B
      transcription/translation mixtures in the presence of ER-derived microsomal
      membranes strongly suggested that p7B is an integral membrane protein. Both
      characteristics of these two small MPs forming the double gene block (DGB) of
      MNSV are discussed in the context of the intra- and intercellular movement of
      carmovirus.

PMID- 16950493
TI  - Characterization of shock in a hamster model of hantavirus infection.
AB  - Human hantavirus cardiopulmonary syndrome (HCPS) due to Andes, sin nombre and
      other hantaviruses is characterized by severe pulmonary capillary leak and
      cardiogenic shock. Hamsters, the only animal manifesting HCPS-like disease, were
      instrumented with radiotelemeters that enabled ambulatory intracarotid blood
      pressure recording within an animal biosafety level-4 facility. Following
      infection with Andes virus, blood pressure and heart rate decreased slowly in a
      biphasic manner during the first 7 days of infection, followed by a rapid fall in
      pressure and rapid increase in heart rate during the 10-20 h preceding death on
      day 9 or 10. The preterminal narrowing of pulse pressure was consistent with a
      cardiogenic impairment. Heart rate variability analysis implicated increased
      sympathetic nervous system activity as seen in human HCPS. The hamster model of
      HCPS mimics not only the pulmonary capillary leak but also the hypotension
      characteristic of human HCPS.

PMID- 16950494
TI  - Phage-displayed peptides having antigenic similarities with porcine epidemic
      diarrhea virus (PEDV) neutralizing epitopes.
AB  - Seven-mer phage random peptide libraries were panned against 2C10, a monoclonal
      antibody that showed neutralizing activities against PEDV. Recombinant M13 phages
      displaying the peptides SHRLP(Y/Q)(P/V) or GPRPVTH on the g3p minor coat protein
      showed strong binding affinity with 2C10 (70% and 30% of recovered phages,
      respectively) after multiple panning. Sequence analysis suggested that these
      peptides are similar with (1368)GPRLQPY(1374) found at the carboxy-terminal of
      the S protein. In neutralization inhibition assays, the two peptide motifs and a
      24-mer synthetic peptide corresponding to the C-terminal endodomain of PEDV S
      protein were observed to compete for the antigen binding site of 2C10, as
      demonstrated by the loss or reduction of neutralizing activity of the monoclonal
      antibody. This new finding suggests that the newly discovered peptide motifs
      mimic a neutralizing epitope PEDV.

PMID- 16950495
TI  - Variability of the colloidal molybdate reactive phosphorous concentrations in
      freshwaters.
AB  - Colloidal-size particles play an important, yet not very well understood, role in
      the speciation of phosphate in freshwaters. This study assesses the size
      distribution of molybdate reactive phosphorous in various 1.2 microm-filtered
      freshwaters using cross-flow filtration. Concurrently, colloid size was
      determined by a single particle counter technique, and mineralogical composition
      by a combination of transmission electronic microscopy coupled with energy
      dispersive spectroscopy and selected area electron diffraction. The percentage of
      colloidal molybdate reactive phosphorous varied a great deal in the samples
      studied: it ranged from 26% down to only 3%. A direct comparison of the
      percentages of colloidal-P can be misleading. The simultaneous determination of
      the amount, size distribution and mineralogical composition of the colloids
      present in the water bodies proved to be essential for interpreting the results.
      The causes of the observed variation were numerous and were site-dependent.

PMID- 16950496
TI  - Spatio-temporal kinetics of growth hormone receptor signaling in single cells
      using FRET microscopy.
AB  - The growth hormone (GH) receptor (R)-mediated JAK2 (Janus kinase-2)-STAT5
      (signaling transducer and activator of transcription-5) pathway involves a
      cascade of protein-protein interactions and tyrosine phosphorylations that occur
      in a spatially and temporally sensitive manner in cells. To study GHR
      dimerization or GH-induced conformational change of predimerized GHRs and STAT5
      activation kinetics in intact cells, fluorescence resonance energy transfer
      (FRET) and live-cell imaging methods were employed. FRET measurements at the
      membrane of HEK-293T cells co-expressing GHRs tagged at the C-terminus with cyan
      (C) and yellow (Y) fluorescent proteins (FPs) revealed transient GHR dimerization
      lasting 2-3 min, with a maximum at 3 min after GH stimulation, which was
      sufficient to induce STAT5 activation. The transient nature of the dimerization
      or GH-induced conformational change of predimerized GHRs kinetics was not a
      result of GHR internalization, as neither potassium- nor cholesterol-depletion
      treatments prolonged the FRET signal. YFP-tagged STAT5 recruitment to the
      membrane, binding to GHR-CFP, and phosphorylation, occurred within minutes of GH
      stimulation. Activated STAT5a-YFP did not show nuclear accumulation, despite
      nuclear pSTAT5 increase, suggesting high turnover of STAT5 nuclear shuttling.
      Although GHR dimerization and STAT5 activation have been reported previously,
      this is the first spatially resolved demonstration of GHR-signaling kinetics in
      intact cells.

PMID- 16950497
TI  - Bioremediation of cadmium contaminated soil using symbiosis between leguminous
      plant and recombinant rhizobia with the MTL4 and the PCS genes.
AB  - Cadmium contamination in rice grains is one of the important issues in Asian
      countries. We have developed a novel bio-remediation system based on the
      symbiosis between leguminous plant and genetically engineered rhizobia. We
      designed two types of recombinant rhizobia, carrying two genes, synthetic
      tetrameric metallothionein (MTL4) and cDNA encoding phytochelatin synthase from
      Arabidopsis thaliana (AtPCS). The MTL4 and AtPCS genes were transferred to
      Mesorhizobium huakuii subsp. rengei B3, which can infect and form nodules on
      Chinese milk vetch, Astragalus sinicus. The two genes were fused to the nolB or
      nifH promoter, which generated nodule specific expression of these genes in
      strain B3. The two recombinant strains, B3(pMPnolBMTL4nifHPCS) and
      B3::nifHMTL4(pMPnifHPCS), showed 25 and 12-fold increase in Cd concentration, in
      the free-living cells, respectively. When these recombinant strains established
      the symbiotic relationship with A. sinicus, the symbionts increased Cd
      accumulation in nodules by two-fold in hydroponic culture. The expression of the
      both MTL4 and AtPCS genes showed additive effect on cadmium accumulation in
      nodules. We also applied these recombinant bacteria to rice paddy soil polluted
      with Cd (1mgkg(-1) dry weight soil). The accumulation of Cd increased not only in
      nodules but also in the roots of A. sinicus infected by the recombinant rhizobia.
      The accumulation of Cd in the plant roots infected by B3(pMPnolBMTL4nifHPCS)
      achieved three-fold than that by the wild-type B3. After two months of
      cultivation of the symbiont, a maximum of 9% of Cd in paddy soil was removed.
      Thus, the symbiosis will be useful in phytoremediation for heavy metals.

PMID- 16950498
TI  - The primate subarcuate fossa and its relationship to the semicircular canals part
      I: prenatal growth.
AB  - Studies have reported a functional link between the arc size of the semicircular
      canals and locomotor agility across adult primates. However, canal size is
      spatially interlinked with the subarcuate fossa. This fossa can house the
      petrosal lobule of the paraflocculus, which also plays a role in coordinating
      head and eye movements. Consequently, it could be that it is the size of the
      petrosal lobule and fossa that are directly associated with locomotor agility,
      and not canal arc size. The apparent association of the latter would only follow
      from the spatial requirement of the canals to accommodate a suitably enlarged
      subarcuate fossa and petrosal lobule. This study aims to test the ontogenetic
      basis of this argument by examining high-resolution magnetic resonance images of
      fetal samples of Homo sapiens, Macaca nemestrina, and Alouatta caraya.
      Falsifiable null hypotheses examined are (1) that development of the subarcuate
      fossa is initiated by growth of the petrosal lobule, and (2) that growth of the
      semicircular canals and of the subarcuate fossa are independent. The findings
      confirm that the subarcuate fossa forms independently of a petrosal lobule in all
      three species, thereby falsifying the first hypothesis. Significant correlations
      were observed between size variables of the semicircular canals and the
      subarcuate fossa, particularly between the anterior canal and the opening of the
      fossa. These results falsify the hypothesis that the canals and fossa grow
      entirely independently. In the human sample, canal growth outpaces fossa growth,
      possibly because no petrosal lobule is present in humans. In the other two
      species, the subarcuate fossa simply seems to fill the space made available by
      canal growth. However, fossa enlargement cannot be excluded as an influence on
      size increase in the canals. Nevertheless, taken together, the results suggest
      that canal size is unlikely to be determined primarily by the spatial
      requirements of the subarcuate fossa and petrosal lobule, rather than by sensory
      demands reflected in the empirically established link with locomotor agility.

PMID- 16950499
TI  - The integration profile of EIAV-based vectors.
AB  - Lentiviral vectors based on equine infectious anemia virus (EIAV) stably
      integrate into dividing and nondividing cells such as neurons, conferring long
      term expression of their transgene. The integration profile of an EIAV vector was
      analyzed in dividing HEK293T cells, alongside an HIV-1 vector as a control, and
      compared to a random dataset generated in silico. A multivariate regression model
      was generated and the influence of the following parameters on integration site
      selection determined: (a) within/not within a gene, (b) GC content within 20 kb,
      (c) within 10 kb of a CpG island, (d) gene density within a 2-Mb window, and (e)
      chromosome number. The majority of the EIAV integration sites (68%; n = 458) and
      HIV-1 integration sites (72%; n = 162) were within a gene, and both vectors
      favored AT-rich regions. Sites within genes were examined using a second model to
      determine the influence of the gene-specific parameters, gene region, and
      transcriptional activity. Both EIAV and HIV-1 vectors preferentially integrated
      within active genes. Unlike the gammaretrovirus MLV, EIAV and HIV-1 vectors do
      not integrate preferentially into the promoter region or the 5' end of the
      transcription unit.

PMID- 16950500
TI  - Spatial distribution of lead in human primary teeth as a biomarker of pre- and
      neonatal lead exposure.
AB  - Lead remains one of the most hazardous toxins in our environment. Because the
      toxic effects of lead are most prominent during early development, it is
      important to develop a suitable biomarker for lead exposure during the pre- and
      neonatal periods. In the present study, the spatial distribution of lead was
      measured in the enamel and dentine of ten human primary teeth using laser
      ablation-inductively coupled plasma-mass spectrometry. The neonatal line,
      visualized using confocal laser scanning microscopy, was used to demarcate the
      pre- and postnatal regions of the sample teeth. Lead levels in pre- and
      postnatally formed enamel and dentine were compared to blood-lead levels measured
      at birth and one year of age for four of these participants. Mean dentine-lead
      levels ranged from 0.17+/-0.02 to 5.60+/-1.79 microg/g, and mean enamel-lead
      levels ranged from 0.04+/-0.01 to 1.47+/-0.20 microg/g. The results of this
      preliminary study showed that the spatial distribution of lead in dentine
      reflected the blood-lead levels. The present study demonstrates a methodology
      where the spatial distribution of lead in the dentine of human primary teeth may
      be used to obtain temporal information of environmental lead exposure during the
      pre- and neonatal periods.

PMID- 16950501
TI  - A microscopic survey on the efficiency of well-known routine chemical fixatives
      on cryosections.
AB  - This study was designed to analyze and compare tissue preservation efficiency of
      acetone (AC), formaldehyde (FA) and paraformaldehyde (PFA) on cryosections.
      Brain, kidney, heart and liver tissue of adult Balb/c mice were fixed with either
      FA or PFA prior to cryosectioning, or fixed with AC alone immediately after
      cryosectioning. Hematoxylin and eosin staining showed that AC is a poor fixative
      in preserving the general tissue and cellular organization. PFA, and to a lesser
      extent FA, produced significantly better results. Another set of cryosections
      were further analyzed to test the properties of those fixatives to preserve
      proteins from specific cell structures. Cytokeratin filaments, F-actin filaments
      and nuclei were immunolabeled and examined using confocal microscopy. Results
      demonstrated that, overall, PFA is the best fixative tested. However, FA fixation
      gave poor results in preserving neuronal tissues. Immunofluorescence confirmed
      the inefficiency of AC fixation, after which no specific labelling of cytokeratin
      filaments was detectable. Nevertheless, actin filaments were detectable on AC
      fixed samples, a finding that was supported by the quantification of fluorescein
      phalloidin binding to F-actin. Overall, the data suggest that AC fixation is
      unacceptable for preservation of most samples, whereas FA and PFA fixation should
      be chosen according to the tissues and proteins to be studied.

PMID- 16950502
TI  - Effect of the 5-HT(6) serotonin antagonist MS-245 on the actions of (-)nicotine.
AB  - The 5-HT(6) serotonin receptor antagonist MS-245 neither substitutes for nor
      antagonizes the discriminative stimulus effects of (-)nicotine. However, MS-245
      was shown to enhance the potency of (-)nicotine in Sprague-Dawley rats trained to
      discriminate 0.6 mg/kg of (-)nicotine from saline vehicle in a typical two-lever
      drug discrimination paradigm such that a combination of MS-245 (5.0 mg/kg) plus
      the ED(50) dose of (-)nicotine caused the animals to respond as if they had
      received the training dose of (-)nicotine. MS-245 also potentiated the
      hypolocomotor actions, but not the antinociceptive effects, of (-)nicotine in
      mice. The results suggest possible involvement of serotonin-regulated signaling
      mechanisms in certain behavioral effects of nicotine.

PMID- 16950503
TI  - Antidepressant-like effect of lectin from Canavalia brasiliensis (ConBr)
      administered centrally in mice.
AB  - This study investigates the action of the central administration of the lectins
      isolated from Canavalia brasiliensis seeds (ConBr) and from Canavalia ensiformes
      seeds, (Concanavalin A, ConA) in the forced swimming test (FST) in mice. ConBr (1
      10 micro g/site, i.c.v.), but not ConA, produced a decrease in the immobility
      time in the FST (observed at the time points 15, 30, 60 and 120 min after the
      injection), without changing the locomotor activity in the open-field test. The
      effect of ConBr in the FST was dependent on its protein structure integrity.
      ConBr (0.1 micro g/site, i.c.v.) caused a potentiation of the action of
      fluoxetine, a selective 5-HT reuptake inhibitor. The anti-immobility effect
      elicited by ConBr (10 micro g/site, i.c.v.) in the FST was prevented by the
      pretreatment of mice with pindolol (32 mg/kg, a 5-HT(1A/1B) receptor/beta
      adrenoceptor antagonist), NAN-190 (0.5 mg/kg, a 5-HT(1A) receptor antagonist),
      ketanserin (5 mg/kg, a 5-HT(2A/2C) receptor antagonist), sulpiride (50 mg/kg, a
      D(2) receptor antagonist) or yohimbine (1 mg/kg, an alpha(2)-adrenoceptor
      antagonist), but not with SCH 23390 (0.05 mg/kg, a D(1) receptor antagonist) or
      prazosin (1 mg/kg, an alpha(1)-adrenoceptor antagonist). These results indicate
      that the antidepressant-like effect of ConBr in the FST is dependent on its
      interaction with the serotoninergic (via 5-HT(1A) and 5-HT(2)), noradrenergic
      (via alpha(2)-adrenoceptors) and dopaminergic (via D(2) receptors) systems.
      Considering the presence of lectins in the brain and based on the results, it
      will be important to determine a possible role of endogenous lectins in the
      modulation of the central nervous system function.

PMID- 16950504
TI  - Anxiolytic-, antidepressant- and anticonvulsant-like effects of the alkaloid
      montanine isolated from Hippeastrum vittatum.
AB  - Compounds isolated from different members of the Amaryllidaceae family are
      becoming relevant options for the treatment of neurological disorders and
      neurodegenerative diseases. In particular, species of the Hippeastrum genus are
      important source of alkaloids with a wide profile of putative therapeutical
      applications. Here, we report on the behavioral and pharmaco-toxicological
      characterization of montanine, an isoquinoline alkaloid isolated from Hippeastrum
      vittatum, an ornamental plant found throughout the world. In mice, montanine
      showed a LD(50) of 64.7 mg/kg and 67.6 mg/kg for male and female, respectively.
      When given i.p., montanine dose-dependently decreased sodium pentobarbital
      induced sleep, protected against pentylenetetrazole-provoked convulsions,
      increased the number of entries and the time spent in the open arms of an
      elevated plus maze and augmented the time spent struggling during a forced
      swimming test. When given immediately after inhibitory avoidance training,
      montanine did not affect avoidance memory retention in rats. Our results suggest
      that montanine, as other alkaloids isolated from Amaryllidaceae species, has
      psychopharmacological activities including anxiolytic, antidepressive and
      anticonvulsive effects.

PMID- 16950505
TI  - A 2-year evaluation of moisture on microtensile bond strength and nanoleakage.
AB  - OBJECTIVES: This study evaluated the effect of moisture on the resin-dentin mu
      bond strength (BS) and silver nitrate uptake (SNU) of three adhesive systems
      (Single Bond, One-Step and Syntac Single Component) soon after bonding (IM) and
      after 2 years of water storage (2Y). METHODS: Dentin surfaces were bonded on a
      dry (D), moist (W) or over-wet surfaces (OW). After restorations were
      constructed, specimens were stored in water (37 degrees C/24h). Resin-dentin
      sticks were prepared (0.8mm(2)) and they were divided for immediate (IM) and 2
      year storage (2Y) testing. Half of the specimens from each period of time were
      tested in tension at 0.5mm/min and the other half was immersed in silver nitrate
      and examined by SEM-EDX. The data was analyzed by three-way repeated measures
      ANOVA and Tukey's tests (alpha=0.05). RESULTS: The overall BS (MPa) in the IM
      group under W condition was higher than in D and OW groups. After 2Y, the BS in W
      was lower than in the IM group, however higher than in the D and OW for OS and
      SB. The overall silver nitrate deposition (%) in the IM group under D, W and OW
      were similar. In the 2Y groups, the nanoleakage was higher than IM groups,
      however the increase was less pronounced in the W condition. SIGNIFICANCE: Higher
      BS and a significantly lower nitrate uptake were observed for IM groups, for OS
      and SB. Under W conditions, the BS reduction over time was less pronounced and
      less nitrate uptake occurred.

PMID- 16950507
TI  - Ion-imprinted beads for molecular recognition based mercury removal from human
      serum.
AB  - The aim of this study is to prepare ion-imprinted polymers which can be used for
      the selective removal of mercury ions [Hg(2+)] from human serum. N-Methacryloyl
      (L)-cysteine (MAC) was chosen as the complexing monomer. In the first step,
      Hg(2+) was complexed with MAC and the Hg(2+)-imprinted poly(hydroxyethyl
      methacrylate-N-methacryloyl-(l)-cysteine) (MIP) beads were synthesized by
      suspension polymerization. After that, the template ions (i.e., Hg(2+)) were
      removed using thiourea (0.5%, v/v) in 0.05 M HCl. The specific surface area of
      the MIP beads was found to be 59.04 m(2)/g with a size range of 63-140 micro m in
      diameter and the swelling ratio was 91.5%. According to the elemental analysis
      results, the MIP beads contained 87.0 micro mol MAC/g polymer. The maximum
      adsorption capacity was 0.45 mg Hg(2+)/g beads. The applicability of two kinetic
      models including pseudo-first order and pseudo-second order model was estimated
      on the basis of comparative analysis of the corresponding rate parameters,
      equilibrium capacity and correlation coefficients. Results suggest that
      chemisorption processes could be the rate-limiting step in the adsorption
      process. The relative selectivity coefficients of MIP beads for Hg(2+)/Cd(2+),
      Hg(2+)/Zn(2+) were 14.7 and 21.5 times greater than the non-imprinted (NIP)
      matrix, respectively. The MIP beads could be used many times without decreasing
      in their adsorption capacities significantly.

PMID- 16950506
TI  - Adhesive analysis of voids in Class II composite resin restorations at the axial
      and gingival cavity walls restored under in vivo versus in vitro conditions.
AB  - OBJECTIVES: Adhesive analysis, under the scanning electron microscope of
      microtensile specimens that failed through the adhesive interface, was conducted
      to evaluate the amount of voids present at the axial versus gingival cavity walls
      of class II composite restorations restored under in vivo and in vitro
      conditions. METHODS: Five patients received class II resin composite
      restorations, under in vivo and in vitro conditions. A total of 14 premolar teeth
      yielded 59 (n=59) microtensile adhesive specimens that fractured through the
      adhesive interface. The fractured surfaces of all specimens were examined and the
      % area of voids was measured. RESULTS: Voids at the adhesive joint were highly
      predictive of bond strengths. An increase in the number of voids resulted in a
      decrease in the microtensile bond strength. The area of voids at the adhesive
      interface was as follows: in vivo axial 13.6+/-25.6% (n=12); in vivo gingival
      48.8+/-29.2% (n=12); in vitro axial 0.0+/-0.0% (n=19) and in vitro gingival
      11.7+/-17.6% (n=16). SIGNIFICANCE: Composite resin may bond differently to dentin
      depending upon the amount of voids and the cavity wall involved. The bond to the
      gingival wall was not as reliable as the bond to the axial wall. An increase in
      the amount of surface voids was a major factor for reducing microtensile bond
      strengths of adhesive to dentin.

PMID- 16950509
TI  - Characterization of inositol 1,4,5-trisphosphate (IP3) receptor subtypes at rat
      colonic epithelium.
AB  - The aim of the present study was the characterization of the subtypes of inositol
      1,4,5-trisphosphate receptors (IP3R) in rat colonic epithelium. A monoclonal
      antibody against IP3R1 did not stain the colonic epithelial cells. In contrast,
      IP3R2 and IP3R3 were found within the epithelium; however, with a distinct
      intracellular localization and differences in their distribution along the crypt
      axis. IP3R2 immunoreactivity was found within the nuclei of the epithelial cells.
      The signal was distributed all over the nucleus and not restricted to the nuclear
      envelope as demonstrated by counterstaining with lamin B1 and electron
      microscopical examination after immunogold labelling. In contrast, an antibody
      against IP3R3 stained the epithelial cells mostly in their apical half in
      accordance with the typical localization of IP3R in organelles such as the
      endoplasmic reticulum. In addition, there was a gradient from the surface region
      towards the crypt fundus, where the IP3R3 signal could not be detected. Despite
      the strong IP3R3-gradient, in saponin-permeabilized colonic crypts exogenously
      administered IP3 or adenophostin A evoked a similar depletion of mag-fura-2
      loaded intracellular Ca2+ stores in crypt and surface cells suggesting a
      contribution of the nuclear IP3R2 to the Ca2+ release. This conclusion was
      confirmed by experiments with isolated nuclei from colonic epithelium, at which
      IP3 was able to induce changes in the Ca2+ concentration, which were inhibited by
      2-aminoethoxy-diphenylborate (2-APB), a blocker of IP3 receptors. These results
      demonstrate that the colonic epithelial cells undergo changes in IP3R subtype
      expression during differentiation.

PMID- 16950508
TI  - Stimulation of in vivo angiogenesis using dual growth factor-loaded crosslinked
      glycosaminoglycan hydrogels.
AB  - Crosslinked, chemically modified hyaluronan (HA) hydrogels pre-loaded with two
      cytokine growth factors, vascular endothelial growth factor (VEGF) and
      angiopoietin-1 (Ang-1), were employed to elicit new microvessel growth in vivo,
      in both the presence and absence of heparin (Hp) in the gels. HA hydrogel film
      samples were surgically implanted in the ear pinnae of mice, and the ears were
      harvested at 7 or 14 days post-implantation. Analysis of neovascularization
      showed that each of the treatment groups receiving an implant, except for HA/Hp
      at day 14, demonstrated significantly more microvessel density than control ears
      undergoing surgery but receiving no implant (p<0.015). Treatment groups receiving
      either Ang-1 alone, or aqueous co-delivery of both Ang-1 and VEGF, were
      statistically unchanged with time. In contrast, film delivery of both growth
      factors produced continuing increases in vascularization from day 7 to day 14 in
      the absence of Hp, but decreases in its presence. However, presentation of both
      VEGF and Ang-1 in crosslinked HA gels containing Hp generated intact microvessel
      beds with well-defined borders. The HA hydrogels containing Ang-1+VEGF produced
      the greatest angiogenic response of any treatment group tested at day 14 (NI=7.44
      in the absence of Hp and 4.67 in its presence, where NI is a neovascularization
      index). Even in the presence of Hp, this had 29% greater vessel density than the
      next largest treatment group receiving HA/Hp+VEGF (NI=3.61, p=0.04). New
      therapeutic approaches for numerous pathologies could be notably enhanced by the
      localized, sustained angiogenic response produced by release of both VEGF and Ang
      1 from crosslinked HA films.

PMID- 16950510
TI  - Activity-independent intracellular Ca2+ oscillations are spontaneously generated
      by ventral spinal neurons during development in vitro.
AB  - Within the CNS, distinct neurons may rely on different processes to modulate
      cytosolic Ca2+ depending on the network developmental phase. In particular, in
      the immature spinal cord, synchronous electrical discharges are coupled with
      biochemical signals triggered by intracellular Ca2+ waves. Nevertheless, the
      presence of neuronal-specific Ca2+ elevations independent from synaptic activity
      within mammalian spinal networks has not yet been described. The present report
      is the first description of repetitive calcium events generated by discrete
      ventral spinal neurons maintained in organotypic culture during in vitro
      maturation stages crucial for network evolution. Ventral interneurons in one
      third of slices displayed spontaneous intracellular calcium transients suppressed
      by calcium-free extracellular solution or by application of cobalt, and resistant
      to blockers of network activity like TTX, CNQX, APV, strychnine or bicuculline.
      Our data suggest a primary role for mitochondria in intracellular calcium
      oscillations, because CCCP, that selectively collapses the mitochondrial
      electrochemical gradient, eliminated the ability of these neurons to show
      activity-independent calcium oscillations. Likewise, CGP-37157, a blocker of
      mitochondrial Na+/Ca2+ exchanger, inhibited oscillations in the majority of
      neurons. We propose that spontaneous Ca2+ transients, dynamically regulated by
      mitochondria, occurred in a discrete cluster of interneurons possibly to guide
      the development of synaptic connections.

PMID- 16950511
TI  - Nitric oxide induces promyelocytic cell growth arrest and apoptosis through
      deactivation of Akt pathway.
AB  - It is NO that mediates the inhibitory effect of IFN-gamma, MIP-1alpha and
      TNFalpha on hematopoiesis. However, the mechanism for NO effect on the
      hematopoietic system is likely to not clear. In the current work, we demonstrates
      that NO can directly suppress the colony formation of granulocyte/macrophage in
      vitro. Using a granulocyte/macrophage progenitor (GMP) model, HL-60 cell line, we
      show that NO inhibits the proliferation of HL-60 cells by inducing G0/G1 arrest
      and apoptosis in a dose- and time-dependent manner. Exposure of HL-60 cells to
      1mM SNP for 2-48h results in marked decrease in Akt activation and Bad
      phosphorylation. Constitutively active Akt overexpression reduces NO-induced
      apoptosis and cell cycle arrest in HL-60 cells. A further investigation on
      apoptosis related protein shows that NO induces Bid cleavage and Bax expression
      but down-regulates the expression of Bcl-2 and Bcl-xL. We also demonstrate here
      that G0/G1 arrest is resulted from NO-induced disruption of cell cycle balance,
      which is mediated by up-regulation of p21(waf/cip1), p27(kip1) and down
      regulation of cyclin D1, cyclin E. In brief, NO-induced apoptosis and G0/G1
      arrest is mediated through regulation of apoptosis and cell cycle related
      protein, which may depend on Akt deactivation by NO, ultimately led to its
      inhibitory effect on hematopoiesis.

PMID- 16950512
TI  - The role of CD14 during resolution of experimentally induced Staphylococcus
      aureus and Streptococcus uberis mastitis.
AB  - This study was undertaken to investigate the time course of surface expression of
      CD14 on neutrophils and macrophages and to determine their association with
      resolution of inflammatory responses during Staphylococcus aureus and
      Streptococcus uberis experimental mastitis. Infections of the mammary gland
      induce a local immune response characterized by an increase in the total counts
      of CD14+ neutrophils and CD14+ macrophages particularly. On the other hand,
      resolution is accompanied by an increase in relative counts of CD14+ neutrophils,
      CD14+ vacuolized macrophages and apoptotic neutrophils. Following the immune
      reaction of mammary gland against Gram-negative/positive bacteria is very
      similar. Between the apoptotic and CD14+ neutrophils a high correlation was
      measured during the whole experimental period (S. aureus: r=0.64; S. uberis:
      r=0.61; P<0.05). Using anti-CD14 monoclonal antibodies in vitro suggested the
      involving of the CD14 surface receptor in recognition of apoptotic neutrophils by
      macrophages.

PMID- 16950513
TI  - Effects of repeated maternal separation on anxiety- and depression-related
      phenotypes in different mouse strains.
AB  - Genetic factors and early life adversity both play a major role in the etiology
      of mood and anxiety disorders. Previous studies have shown that postnatal
      maternal separation (MS) can produce lasting abnormalities in emotion-related
      behavior and neuroendocrine responses to stress in rodents. The present study
      sought to examine the effects of repeated MS in eight different inbred strains of
      mice (129S1/SvImJ, 129P3/J, A/J, BALB/cJ, BALB/cByJ C57BL/6J, DBA/2J, FVB/NJ).
      Pups were separated from their dam and littermates for 180 min/day ('MS') or 15
      min/day ('handling'), or left undisturbed ('facility-reared') from postnatal days
      P0-P13, and tested as adults for anxiety- and depression-related behaviors.
      Results demonstrated no clear and consistent effects of MS or handling on
      behavioral phenotypes in any of the strains tested. In all strains, MS produced
      an increase in maternal care on reunion with pups, which may have modified MS
      effects. Data demonstrate that the MS procedure employed does not provide a
      robust model of early life stress effects on the anxiety- and depression-related
      behaviors in the mouse strains tested.

PMID- 16950515
TI  - The role of nitric oxide in the post-ischemic revascularization process.
AB  - Following arterial occlusion, blood vessels respond by sprouting new capillaries
      (i.e. angiogenesis) and by growing and remodelling pre-existing arterioles into
      physiologically relevant arteries (i.e. arteriogenesis). The importance of nitric
      oxide (NO) in ischemia-induced angiogenesis is supported by 4 main findings: (i)
      the ischemic limb shows an increase in endothelial nitric oxide synthase (eNOS)
      mRNA, protein expression and NO synthesis; (ii) the absence of the NO pathway (by
      either pharmacological inhibition or gene disruption of eNOS) abolishes ischemia
      induced angiogenesis; (iii) supplementation of NO by the use of exogenous sources
      restores ischemia-induced angiogenesis; and (iv) cardiovascular diseases
      associated with decreased NO synthesis show impaired ischemia-induced
      angiogenesis. Thus, impairment of the NO metabolic pathway could be one of the
      main contributing factors for the development of peripheral arterial occlusive
      disease. The restoration of normal NO levels in diseased arteries is therefore a
      major therapeutic goal; this could be achieved by supplementation with exogenous
      NO or by strategies designed to increase the concentration of endogenous NO.

PMID- 16950514
TI  - Effect of manganese exposure on the neuroendocrine system in welders.
AB  - To evaluate the effect of occupational exposure to manganese (Mn) on serum
      prolactin (PRL) and the interrelationship among other hypophyseal-pituitary
      hormones, a cross-sectional study was conducted on 251 welders and 100 age
      matched, office workers. We analyzed serum PRL, dopamine (DA), thyroid
      stimulating hormone releasing hormone (TRH), follicle stimulating hormone (FSH),
      luteinizing hormone (LH) and testosterone (TST) and measured current airborne Mn
      concentration in the welders. Cumulative exposure index (CEI) of airborne Mn was
      calculated. CEI and the present Mn level of the welders were 1.4+/-1.1mg/m3 year
      (range: 0.0-4.9) and 0.4+/-3.84 mg/m3 (range: 0.0-3.8), respectively. TRH, FSH
      and LH were higher in welders (5.08 pg/ml, 7.40 and 4.91 mIU/ml, respectively)
      than in office workers (3.91 pg/ml, 6.15 and 4.00 mIU/ml, respectively) (p<0.05).
      DA was decreased and TRH was increased significantly with increasing CEI. DA
      increased up to CEI 2.0mg/m3 year or mean Mn level up to 0.2mg/m3, then
      decreased. PRL showed increasing tendency above the CEI and mean Mn level at
      which DA started to decrease. PRL was positively associated with DA in the office
      workers. However, such a normal feedback control of DA on PRL was not observed in
      the welders. Structural equation model (SEM) analysis showed that CEI was
      positively related to TRH and negatively related to DA. TRH increased PRL. PRL
      increased LH and perhaps FSH, and on the other hand, decreased TST. These results
      showed that Mn suppresses the inhibitory feedback control of DA on the
      hypophyseal-pituitary axis. In conclusion, we postulate that suppressed
      dopaminergic inhibitory function on the hypophyseal-pituitary axis might be the
      mechanism for the increased PRL exhibited in the welders.

PMID- 16950516
TI  - Efficacy of psychoeducational approaches on bipolar disorders: a review of the
      literature.
AB  - BACKGROUND: To evaluate the efficacy of psychoeducation in the treatment of
      bipolar disorder according to specific therapeutic targets such as treatment
      compliance, patients' and families' knowledge of the illness and its treatments,
      relapse prevention, symptomatic (depressive or (hypo)manic) phases of the illness
      or social and occupational functioning. METHODS: A systematic review of the
      literature published on psychoeducation up to July 2006 was carried out using the
      main electronic data bases (Medline, PubMed). The key words employed included
      bipolar disorder, psychoeducation, depression, mania, relapse prevention and
      treatment compliance. RESULTS: Although the methodological shortcomings of the
      early studies must be taken into account, most data accumulated to date suggest
      that psychoeducation, used alone or as a component of more complex interventions,
      makes it possible to improve the course of the illness, notably by increasing the
      patients' and their families' knowledge of the disorder and of treatment options,
      by decreasing the risk of (hypo)manic or depressive relapse and of
      hospitalization and by improving treatment compliance. LIMITATIONS: More studies
      based solely on psychoeducation, rather than psychoeducation as part of a
      multicomponent approach, are needed to confirm the efficacy of PE reported to
      date. CONCLUSIONS: Given the results published to date, psychoeducation should be
      part of the integrated treatment of bipolar disorder. As a complement to
      pharmacotherapy, psychoeducation delivered individually or in a group setting
      constitutes a first-line psychological intervention. Applicable to a majority of
      patients and their families, it can be delivered by a wide range of health
      professionals trained in this approach.

PMID- 16950517
TI  - Immunization with autologous CD46 generates a strong autoantibody response in
      rats that targets spermatozoa.
AB  - CD46, a membrane complement regulator, has been implicated as pathogen receptor,
      T cell activator and contributor to spermatozoa-egg interactions. In man, a role
      in the fertilization process was suggested by its localization on the acrosome.
      In rodents, CD46 is expressed only on the spermatozoal acrosome, suggesting an
      essential role at this site. This restricted expression led us to ask whether
      immunization with CD46 would generate anti-CD46 antibody responses that might
      target spermatozoa and influence fertility. We immunized male and female rats
      with rat CD46. Strong immune responses were generated in all rats and immune sera
      stained CD46 in testis extracts and in situ in testis and sperm. Incubation of
      spermatozoa with immune sera caused deposition of immunoglobulin and C3b in an
      acrosome pattern and reduced motility. We mated immune male rats with naive
      females and female immune rats with naive males. The incidence of pregnancy and
      number of fetuses were not different in matings involving immune male or female
      rats compared to controls. Testis sections from immune rats revealed no
      immunoglobulin deposition on CD46-positive sperm precursors, suggesting that
      acrosomal CD46 was inaccessible in this location. A minority of spermatozoa
      harvested from epididymis of immune rats had immunoglobulin and C3b bound to the
      acrosome, suggesting that anti-CD46, present in genital tract fluids, bound after
      acrosome reaction. These data demonstrate that the restricted expression of CD46
      allows strong anti-CD46 responses in rats that target spermatozoa in vitro and in
      vivo. The anti-CD46 response did not influence fertility, perhaps reflecting the
      considerable redundancy for fertilization in rodents.

PMID- 16950518
TI  - Early pregnancy decidual lymphocytes beside perforin use Fas ligand (FasL)
      mediated cytotoxicity.
AB  - Decidual natural killer (NK) cells are the predominant lymphocytes at the
      maternal-fetal interface. They are involved in defense against virally infected,
      parasitized and transformed cells and may contribute to the control of
      trophoblast invasion. The presence of perforin and other possible cytolytic
      mediators suggests these functions. Cytolytic mechanisms of unstimulated and Th1
      cytokine stimulated decidual lymphocytes (DL), as well as purified decidual
      CD56(+) cells, were analyzed against NK sensitive and resistant targets. DL were
      isolated from decidual mononuclear cells (DMC) cultured in the medium only or in
      the presence of Th1 cytokines: IL-2, IL-12, IL-15, IL-18 and their combinations
      (IL-12/IL-18 or IL-15/IL-18). Fas ligand (FasL), perforin and granzyme B mRNAs
      expression and cytotoxicity were analyzed by flow cytometry and/or RT-PCR. DL
      (containing 72.19+/-7.53% of CD56(+) cells), obtained from 18h-cultured DMC in
      the medium only, expressed perforin, FasL and granzyme B mRNAs and lysed the NK
      sensitive K-562 cell line, and also the NK-resistant P815 and P815-Fas
      transfected cell lines. Concanamycin A, a blocker of granule exocytosis,
      decreased significantly K-562 lysis, but not P815 lysis. However, the addition of
      anti-FasL antibody diminished significantly P815 lysis as well. IL-2 and IL-15,
      known inducers of perforin and FasL mRNAs and protein expression, could not
      additionally increase P 815 cell lysis by DL cultured within DMC. These results
      suggest that DL cultured in DMC for 18h, have the characteristics of lymphokine
      activated killer (LAK) cells and are able to use efficiently both the perforin
      and the FasL cytolytic pathways.

PMID- 16950519
TI  - Formulation with CpG ODN enhances antibody responses to an equine influenza virus
      vaccine.
AB  - Previous studies have shown that protection against equine influenza virus (EIV)
      is partially mediated by virus-specific IgGa and IgGb. In this study we tested
      whether addition of a CpG ODN formulation to a commercial killed virus vaccine
      would enhance EIV-specific IgGa and IgGb antibody responses, and improve
      protection against an experimental EIV challenge. Thirty naive horses were
      assigned to one of three groups and vaccinated as follows: 10 were given vaccine
      (Encevac TC4, Intervet Inc.) alone, 10 were given vaccine plus 0.25 mg CpG ODN
      2007 formulated with 30% Emulsigen (CpG/Em), and 10 controls were given saline.
      All horses were challenged with live virus 12 weeks after the final vaccination.
      Antibody responses were tested by single radial hemolysis (SRH) and ELISA, and
      protection was evaluated by determination of temperature, coughing, and clinical
      scores. Killed virus vaccine combined with CpG/Em induced significantly greater
      serologic responses than did the vaccine alone. All antibody isotypes tested
      increased after the addition of CpG/Em, although no shift in relative antibody
      isotypes concentrations was detected. Vaccination significantly improved
      protection against challenge but the differences between the two vaccine groups
      were not statistically significant. This study is the first demonstration that
      CpG/Em enhances antigen-specific antibody responses in horses and supports its
      potential to be used as an adjuvant for vaccines against equine infections.

PMID- 16950520
TI  - Lower respiratory tract foreign bodies: a retrospective review of morbidity,
      mortality and first aid management.
AB  - OBJECTIVES: The authors describe 28 pediatric cases of foreign body inhalation
      requiring treatment in intensive care units between 1987 and 1999. The purpose of
      this study was: (1) to analyze the circumstances, diagnostic difficulties and
      initial treatment of serious foreign bodies and (2) to compare our series with
      other literature descriptions and define principles for optimal prevention and
      initial treatment. METHODS: Twenty-one children presented a penetration syndrome,
      which was responsible in 13 cases for asphyxia with cardiorespiratory arrest. All
      these children died, regardless of the initial treatment. Seven children were
      hospitalized for apparent asthmatic symptoms that did not respond to traditional
      treatment. RESULTS: The inefficiency of external extraction methods like the
      Heimlich maneuver and the mean delay between clinical signs and initial treatment
      lead us to propose a new strategy for the emergency treatment of foreign bodies
      with asphyxia. CONCLUSIONS: We recommend that emergency teams promote the use of
      a laryngoscope and Magill forceps. Flexible endoscopy is still recommended as the
      appropriate diagnostic tool to eliminate doubt in the case of a first severe
      asthma attack.

PMID- 16950521
TI  - Polymorphism of the CD14 gene in perennial allergic rhinitis.
AB  - OBJECTIVES: Allergic diseases have strong genetic backgrounds. Recently, a C-T
      polymorphism in the promoter region of CD14 has been associated with phenotypes
      of atopy in some populations. The aim of this study was to investigate the
      association of CD14/-159 polymorphism with total serum IgE levels and number of
      positive skin prick tests in Korean population with perennial allergic rhinitis.
      STUDY DESIGN: Prospective study. METHODS: Deoxyribonucleic acid obtained from 164
      children with perennial allergic rhinitis and 160 healthy controls were typed for
      the promoter polymorphism of CD14 gene at position -159 by restriction fragment
      length polymorphism analysis. Genotype frequencies, total serum IgE levels, and
      the number of positive skin tests for each genotype were compared. RESULTS: There
      were no significant differences in the CD14/-159 genotype frequencies between the
      allergic rhinitis group and the control group. In the skin prick test-positive
      population, the CC homozygotes were associated with higher serum total IgE levels
      and greater number of positive skin tests compared with subjects with CT and TT
      alleles (P<0.05). CONCLUSIONS: The results from the present study suggest that
      CD14/-159 polymorphism may play a role in the development of perennial allergic
      rhinitis in Korean children.

PMID- 16950522
TI  - Transfection of mammalian cells using linear polyethylenimine is a simple and
      effective means of producing recombinant adeno-associated virus vectors.
AB  - We have developed a simple protocol to transfect mammalian cells using linear
      polyethylenimine (PEI). Our linear PEI protocol is as effective as commercial
      reagents in the transfection of HeLa cells and XDC293 cells, a derivative of
      HEK293 cells, but at a fraction of the cost. Greater than 90% of XDC293 cells and
      98% of HeLa cells transfected using our method were positive for EGFP expression
      as determined by flow cytometery. Our protocol should be useful for many
      different applications such as large-scale production of recombinant protein and
      viruses, which requires transient transfection of mammalian cells in large
      batches. We have used this protocol to produce recombinant adeno-associated virus
      (AAV) in XDC293 cells and in HeLa cells. This requires transient expression of
      three adenovirus gene-products (E2A, E4orf6, and VA RNAs) as well as the AAV
      replication (Rep78, Rep68, Rep52, and Rep40) and capsid (VP1, VP2, and VP3)
      proteins. Production of a recombinant AAV that expresses green fluorescent
      protein was assessed by quantitative PCR and by transduction of HeLa cells.
      Linear PEI is a better transfection reagent than calcium phosphate for the
      production of recombinant AAV in both HEK293 and HeLa cells. In addition, when
      both HeLa and XDC293 cells were by our method, HeLa cells in the absence of E1A
      generated three-fold more recombinant AAV than XDC293 cells, which constitutively
      express E1A.

PMID- 16950523
TI  - Antiviral effect of octyl gallate against DNA and RNA viruses.
AB  - The effects of gallic acid (3,4,5-trihydroxybenzoic acid) and its alkyl esters on
      virus growth and virion infectivity were examined. All the compounds tested
      showed an inhibitory effect on the growth of herpes simplex virus type 1 (HSV-1)
      in HEp-2 or Vero cells. The antiviral activity of gallic acid alkyl esters was
      enhanced by increasing the number of carbon in the alkyl moieties of the
      compounds, reaching maximum at a carbon number of 12 (lauryl gallate), but both
      cytocidal activity and cytopathic effect of the compounds were also significantly
      increased simultaneously. Among these compounds, octyl gallate showed a marked
      antiviral effect with a relatively moderate cytotoxity. In addition, octyl
      gallate suppressed the multiplication of RNA viruses, such as vesicular
      stomatitis virus and poliovirus. Quantitative characterization of the HSV-1
      infection in the presence of octyl gallate revealed that: (1) this reagent can
      directly inactivate HSV-1 (virucidal activity), (2) it suppresses both the
      intracellar multiplication and the release of the virus, (3) it selectively
      accelerates death of the virus-infected cells and (4) the addition of the reagent
      even at 6-h post infection completely abolishes the formation of progeny virus in
      the infected cells.

PMID- 16950524
TI  - Neurobiological effects of intraventricular propionic acid in rats: possible role
      of short chain fatty acids on the pathogenesis and characteristics of autism
      spectrum disorders.
AB  - Clinical observations suggest that certain gut and dietary factors may
      transiently worsen symptoms in autism spectrum disorders (ASD), epilepsy and some
      inheritable metabolic disorders. Propionic acid (PPA) is a short chain fatty acid
      and an important intermediate of cellular metabolism. PPA is also a by-product of
      a subpopulation of human gut enterobacteria and is a common food preservative. We
      examined the behavioural, electrophysiological, neuropathological, and
      biochemical effects of treatment with PPA and related compounds in adult rats.
      Intraventricular infusions of PPA produced reversible repetitive dystonic
      behaviours, hyperactivity, turning behaviour, retropulsion, caudate spiking, and
      the progressive development of limbic kindled seizures, suggesting that this
      compound has central effects. Biochemical analyses of brain homogenates from PPA
      treated rats showed an increase in oxidative stress markers (e.g., lipid
      peroxidation and protein carbonylation) and glutathione S-transferase activity
      coupled with a decrease in glutathione and glutathione peroxidase activity.
      Neurohistological examinations of hippocampus and adjacent white matter (external
      capsule) of PPA treated rats revealed increased reactive astrogliosis (GFAP
      immunoreactivity) and activated microglia (CD68 immunoreactivity) suggestive of a
      neuroinflammatory process. This was coupled with a lack of cytotoxicity (cell
      counts, cleaved caspase 3' immunoreactivity), and an increase in phosphorylated
      CREB immunoreactivity. We propose that some types of autism may be partial forms
      of genetically inherited or acquired disorders involving altered PPA metabolism.
      Thus, intraventricular administration of PPA in rats may provide a means to model
      some aspects of human ASD in rats.

PMID- 16950525
TI  - Vitellogenin synthesis in primary cultures of fish liver cells as endpoint for in
      vitro screening of the (anti)estrogenic activity of chemical substances.
AB  - Concern over possible adverse effects of endocrine-disrupting compounds on fish
      has caused the development of appropriate testing methods. In vitro screening
      assays may provide initial information on endocrine activities of a test compound
      and thereby may direct and optimize subsequent testing. Induction of vitellogenin
      (VTG) is used as a biomarker of exposure of fish to estrogen-active substances.
      Since VTG induction can be measured not only in vivo but also in fish hepatocytes
      in vitro, the use of VTG induction response in isolated fish liver cells has been
      suggested as in vitro screen for identifying estrogenic-active substances. The
      main advantages of the hepatocyte VTG assay are considered its ability to detect
      effects of estrogenic metabolites, since hepatocytes in vitro remain
      metabolically competent, and its ability to detect both estrogenic and anti
      estrogenic effects. In this article, we critically review the current knowledge
      on the VTG response of cultured fish hepatocytes to (anti)estrogenic substances.
      In particular, we discuss the sensitivity, specificity, and variability of the
      VTG hepatocyte assay. In addition, we review the available data on culture
      factors influencing basal and induced VTG production, the response to natural and
      synthetic estrogens as well as to xenoestrogens, the detection of indirect
      estrogens, and the sources of assay variability. The VTG induction in cultured
      fish hepatocytes is clearly influenced by culture conditions (medium composition,
      temperature, etc.) and culture system (hepatocyte monolayers, aggregates, liver
      slices, etc.). The currently available database on estrogen-mediated VTG
      induction in cultured teleost hepatocytes is too small to support conclusive
      statements on whether there exist systematic differences of the VTG response
      between in vitro culture systems, VTG analytical methods or fish species. The VTG
      hepatocyte assay detects sensitively natural and synthetic estrogens, whereas the
      response to xenoestrogens appears to be more variable. The detection of weak
      estrogens can be critical due to the overshadow with cytotoxic concentrations.
      Moreover, the VTG hepatocyte assay is able to detect antiestrogens as well as
      indirect estrogens, i.e substances which require metabolic activation to induce
      an estrogenic response. Nevertheless, more chemicals need to be analysed to
      corroborate this statement. It will be necessary to establish standardized
      protocols to minimize assay variability, and to develop a set of pass-fail
      criteria as well as cut-offs for designating positive and negative responses.

PMID- 16950526
TI  - The cross-validity of the filial obligation scale.
AB  - The filial obligation scale we developed needed examining cross-validity to make
      it more precise. In this study, by examining this scale in an area different from
      the previous study in terms of characteristics (e.g., rural v. urban), we verify
      its cross-validity. The results showed that three factors extracted from factor
      analysis precisely reflected Morioka's theory and the correlation coefficients
      with affiliation and geographic distance that were indicated to be related with
      filial obligation in the previous studies showed significance. The results of
      this study support reliability and validity of this scale.

PMID- 16950527
TI  - Cardiac compression by a thymic cyst.
AB  - A patient with a giant thymic cyst, causing cardiac compression, is presented.
      Thymic cysts are uncommon and often asymptomatic.

PMID- 16950528
TI  - A cross-sectional survey of Australian chicken farms to identify risk factors
      associated with seropositivity to Newcastle-disease virus.
AB  - Several outbreaks of virulent Newcastle-disease occurred in Australia in 1998
      2000. We conducted a cross-sectional survey of 753 Australian chicken farms to
      identify risk factors associated with the seroprevalence of chicken flocks with
      Newcastle-disease virus (NDV). We had a 99.7% response rate to the survey and the
      overall prevalence of NDV seropositive farms was 39.8%. Associations were
      analysed for the layer, chicken-meat and breeder production sectors in sector
      specific logistic-regression models using 187, 198 and 146 farms, respectively.
      In the layer sector, increased risk of seroprevalence was associated with
      increasing age of the chickens, and decreased risk when the nearest-neighbour
      poultry farm was >10 km distant (odds ratio (OR)=0.30). In the chicken-meat
      sector, increased risk of seroprevalence was associated with location in the
      Sydney basin (OR=13.67), eastern Victoria (OR=26.10) or western Victoria
      (OR=5.43), and decreased risk when the nearest-neighbour poultry farm was greater
      than 0.5 km distant (OR=0.34). In the breeder sector, increased risk of
      seroprevalence was associated with increasing age of the chickens, the presence
      of wild birds on the farm (OR=5.28) and location in eastern Victoria (OR=16.19).
      A conditional logistic-regression for 112 pairs of farms matched for age, survey
      region and production sector identified a distance of >1.0 km to the nearest
      neighbour poultry farm (OR=0.24) and ownership by owner 2 (OR=0.02), owner 5
      (OR=0.11) or owner 9 (OR=0.25) as significant in reducing the risk of NDV
      seroprevalence. Our survey found that high levels of biosecurity and hygiene
      practices had been adopted by most farms.

PMID- 16950529
TI  - Cigarette smoking and self-control.
AB  - This paper empirically studies time inconsistent preferences in the context of
      cigarette smoking behavior. With hyperbolic discounting, an individual has time
      inconsistent preferences, which give rise to a lack of self-control, i.e., she
      may perpetually postpone the execution of a plan. This implies that a smoker who
      wants to quit has a demand for control devices, e.g., a smoking ban in public
      areas or a hike in cigarette excise taxes. This paper empirically tests this
      implication, using a sample that is based on survey data from Taiwan. The
      estimation results indicate that a smoker's intention to quit has a positive
      effect on the smoker's support for smoking bans and a cigarette excise tax
      increase. These results lend support to the validity of the time inconsistent
      preferences in the context of cigarette smoking behavior. This casts doubt on the
      validity of the assumption that individuals have time consistent preferences in
      Becker and Murphy's [Becker, G.S., Murphy, K.M., 1988. A theory of rational
      addiction. Journal of Political Economy 96 (4), 675-700] rational addiction
      model.

PMID- 16950530
TI  - Sugars relevant for sourdough fermentation stimulate growth of and bacteriocin
      production by Lactobacillus amylovorus DCE 471.
AB  - The effects of sugars relevant for sourdough fermentation (i.e. glucose,
      fructose, maltose, and sucrose) on the kinetics of the bacteriocin-producing
      Lactobacillus amylovorus DCE 471 strain were assessed. The sugars were applied
      solely or in combination in a sourdough simulation medium during batch
      fermentations at temperature and pH conditions encountered during the production
      of type II sourdoughs. When growing on a single energy source, glucose was
      preferentially consumed by L. amylovorus DCE 471, followed by maltose and
      fructose. The strain was unable to grow on sucrose. In glucose-containing
      mixtures, glucose was always consumed most rapidly by L. amylovorus DCE 471 and
      seemed to steer its growth during the early growth phase, mainly because of the
      delaying effect on maltose consumption. Maltose consumption started only when low
      glucose levels were reached. In all cases, fructose was used as an energy source
      and not as a terminal electron acceptor, since no acetic acid or mannitol were
      produced. Increased bacteriocin titres were observed with binary or ternary sugar
      combinations compared to single energy sources. Thus, the diversity of the energy
      source seemed to stimulate the production of amylovorin L. Cell growth of and
      production of amylovorin L by L. amylovorus DCE 471 paralleled for all sugar
      combinations tested.

PMID- 16950531
TI  - A real-time PCR assay for the enumeration and detection of Zygosaccharomyces
      bailii from wine and fruit juices.
AB  - Zygosaccharomyces bailii is a major food and beverage spoilage organism. Existing
      methods for its detection involve lengthy enrichment techniques and then the
      result does not always differentiate between Z. bailii and Saccharomyces
      cerevisiae. In this work, we developed a quantitative real-time PCR assay for the
      rapid detection of Z. bailii from fruit juices and wine even in the presence of
      non-target DNA. Primers were designed to the gene coding for the D1/D2 loop of
      the 26S ribosomal RNA subunit producing a single PCR product with a melting
      temperature of 83.5 degrees C. As few as 2 cells per ml could be detected by the
      assay in cranberry raspberry and apple juices and 22 cells per ml from grape
      juice. The assay was equally efficient in wine, detecting 6 cells per ml even in
      the presence of 10(7)S. cerevisiae cells. The CFU/ml as determined by plating on
      YM media showed excellent correlation with the CFU/ml established by the QPCR
      assay for all the beverages examined. Unknown samples of Z. bailii were prepared
      in the juices and wine and examined by QPCR. The QPCR estimated cell number was
      in good agreement with the cell counts obtained by plating, the exception being
      the cranberry raspberry juice sample. It was determined by live/dead cell counts
      that the Z. bailii cells were less viable in this juice thus leading to an
      overestimation of CFU/ml by QPCR. However, the correlation was high between QPCR
      and total cell count as determined by fluorescent microscopy. This assay provides
      a rapid and accurate method to establish the levels of the total Z. bailii
      population which consists of both viable and nonviable cells.

PMID- 16950532
TI  - Trehalose as a good candidate for enriching full-length cDNAs in cDNA library
      construction.
AB  - It has been reported that the disaccharide trehalose is capable of increasing the
      thermostability and thermoactivity of reverse transcriptase, and therefore
      improving the length of cDNA synthesis. However, no test has been done on how the
      disaccharide trehalose performs in the context of the entire cDNA synthesis
      processes, or whether it can seamlessly integrate into the commercially available
      cDNA synthesis kit. In this report, we optimized a protocol to incorporate
      trehalose in the Stratagene's cDNA library construction kit in order to
      demonstrate great improvement in cDNA's length (average length of 1.8 kb in the
      trehalose group versus 1.0 kb in the control). Sequence analysis of the cDNA
      clones showed that the addition of trehalose did not increase the error rate of
      the RT products but greatly increase the quantity of full-length in cDNA library.

PMID- 16950533
TI  - A set of UV-inducible autolytic vectors for high throughput screening.
AB  - A high throughput screening scheme is often a prerequisite for directed evolution
      of enzymes or metagenomic analysis of DNA samples. For assaying intracellular
      enzymes of interest (e.g. when Escherichia coli is used), it requires cell lysis
      in many cases, chemical or enzymatic, which can be tedious and cost-consuming. In
      this study, a set of UV-inducible autolytic vectors was constructed to offer a
      simpler means of cell lysis that is free of additional liquid handling. The SRRz
      lysis gene cassette from bacteriophage Lambda was cloned downstream of a UV
      inducible promoter, the recA promoter or the umuDC promoter, and further inserted
      into the backbone of pUC18, and transformed into E. coli BL21 cells. The SRRz
      expression and cell lysis was induced by UV irradiation. For both the recA and
      umuDC promoters, at 30 degrees C the lysis efficiency was found to be consistent
      and above 60% as measured using beta-galactosidase as the reporter. However, at
      37 degrees C the lysis profiles were found to be erratic. UV lysis in 96-well
      plates also produced consistent lysis results that were comparable to those
      obtained by lysozyme treatment, demonstrating the utility of these autolytic
      vectors in high throughput screening. This set of artificial SRRz autolysis units
      should be transferable to other vectors. Surprisingly, it was found that the E.
      coli BL21(DE3) was also partially disrupted under UV irradiation, with a lysis
      efficiency of 44.5% at 30 degrees C, and 22.5% at 37 degrees C.

PMID- 16950534
TI  - Purification of retroviral vectors for clinical application: biological
      implications and technological challenges.
AB  - For centuries mankind led a difficult battle against viruses, the smallest
      infectious agents at the surface of the earth. Nowadays it is possible to use
      viruses for our benefit, both at a prophylactic level in the production of
      vaccines and at a therapeutic level in the promising field of gene therapy.
      Retroviruses were discovered at the end of the 19th century and constitute one of
      the most effective entities for gene transfer and insertion into the genome of
      mammalian cells. This attractive feature has intensified research in retroviral
      vectors development and production over the past years, mainly due to the
      expectations raised by the concept of gene therapy. The demand for high quality
      retroviral vectors that meet standard requisites from the regulatory agencies
      (FDA and EMEA) is therefore increasing, as the technology has moved into clinical
      trials. The development of safer producer cell lines that can be used in large
      scale production will result in the production of large quantities of retroviral
      stocks. Cost-efficient and scalable purification processes are essential for
      production of injectable-grade preparations to achieve final implementation of
      these vectors as therapeutics. Several preparative purification steps already
      established for proteins can certainly be applied to retroviral vectors, in
      particular membrane filtration and chromatographic methods. Nevertheless, the
      special properties of these complex products require technological improvement of
      the existing purification steps and/or development of particular purification
      steps to increase productivity and throughput, while maintaining biological
      activity of the final product. This review focuses on downstream process
      development in relation to the retroviral vectors characteristics and quality
      assessment of retroviral stocks for intended use in gene therapy.

PMID- 16950535
TI  - Development of bioprocess for the production of purified protein derivative with
      Brazilian strains of Mycobacterium tuberculosis for diagnosis use.
AB  - Tuberculin, a purified protein derivative (PPD), when diluted in adequate
      concentration it is utilized for an early detection and to control tuberculosis.
      In Brazil, the PPD is imported and distributed by the Health System in all
      Brazilian regions. This, in addition to eventual delay in delivery caused by the
      legal import process, makes difficult the access of the product to poor
      communities from distant places as Brazil is a geographically a large country.
      Thus, indigenous production of PPD would be very beneficial for the society. This
      work was undertaken with a view to initiate studies towards the development of an
      indigenous technology for PPD production, using the strains of Mycobacterium
      tuberculosis isolated from patients during the course of disease from several
      regions of Brazil. The strain selection criteria for PPD production were the
      sequencing of three immunodominant proteins and the genetic differentiation by
      DNA fingerprinting and grouped by UPGMA program, the capacity of protein
      production in liquid medium, and finally the intradermal injection tests used on
      animal model. Compared to gold standard, the PPD showed similar indurations when
      tested individually, and better results were obtained when products were combined
      in pool. These strategies are discussed in detail in this research.

PMID- 16950536
TI  - Synthesis of triglycerides of phenylalkanoic acids by lipase-catalyzed
      esterification in a solvent-free system.
AB  - Immobilized Candida antarctica lipase B catalyzed the synthesis of triglycerides
      from glycerol and phenylalkanoic acids in a solvent-free system. 4-Phenylbutyric
      acid was the best acyl donor and displayed the highest synthetic rate of
      triphenylbutyrin (glyceryl triphenylbutyrate) at 65 degrees C among various
      phenylalkanoic acids with straight alkyl chains. The external mass transfer
      between the immobilized lipase and the bulk reaction mixture was limited.
      Different methods of removing water during the lipase-catalyzed esterification
      including spontaneous evaporation, the use of saturated salts solutions, and the
      use of molecular sieves were studied. The highest yield of triphenylbutyrin at 65
      degrees C was 98%, by the elimination of water using molecular sieves in a
      solvent-free system. The glycerol was almost completely esterified to
      triphenylbutyrin in excess phenylbutyric acid with various substrate molar
      ratios.

PMID- 16950537
TI  - Development of a one-step ELISA method using an affinity peptide tag specific to
      a hydrophilic polystyrene surface.
AB  - Glutathione S-transferase genetically fused with an affinity peptide tag, PS19
      (RAFIASRRIKRP) having a specific affinity for a hydrophilic polystyrene (PS)
      surface, was preferentially immobilized on a hydrophilic PS (phi-PS) plate
      without suffering from interference by coexisting protein molecules. Furthermore,
      rabbit IgG chemically conjugated with a peptide, KPS19R10, in which (10)Lys in
      PS19 was replaced with Arg and one Lys residue was added at the N-terminus as a
      coupling site for glutaraldehyde, showed a higher immobilization affinity to the
      phi-PS plate than that conjugated with the PS19 peptide. On the basis of these
      findings, the use of a phi-PS plate and peptide tag-linked ligand proteins
      permitted a one-step or two-step enzyme-linked immunosorbent assay (ELISA) to be
      achieved, resulting in a substantial reduction in operational time compared with
      the conventional ELISA method using a hydrophobic PS (pho-PS) plate, while
      maintaining a high sensitivity. Furthermore, the sensitivity was increased to a
      greater extent compared to the conventional ELISA meihod when the one-step ELISA
      was applied to the detection of bovine insulin in a sandwich mode, due to the
      reduced number of washing and incubation steps. The method proposed here would be
      a versatile method for use in various ELISA techniques such as sandwich and
      competitive ELISAs using an antigen, an antibody and streptavidin that are
      genetically fused or chemically conjugated with the PS-specific affinity peptide
      as the ligand protein.

PMID- 16950538
TI  - Phosphorylase coupling as a tool to convert cellobiose into amylose.
AB  - This work aims to establish the enzymatic process to produce amylose from
      cellobiose. Incubation of cellobiose with cellobiose phosphorylase and alpha
      glucan phosphorylase in the presence of maltotetraose and a catalytic amount of
      inorganic phosphate at 45 degrees C for 16 h resulted in the production of linear
      alpha-1,4-glucan with a 19.3% (w/v, against cellobiose weight) yield. The yield
      was successfully improved (32.4%) when mutarotase and glucose oxidase were added
      to remove glucose in the reaction mixture. The weight-average molecular weight of
      the product was precisely controlled from 42 to 720 kDa by changing the initial
      molar ratio of cellobiose to maltotetraose. The combined use of two different
      phosphorylases should be a useful tool in converting beta-1,4-linked
      polysaccharide into alpha-1,4-linked-polysaccharide.

PMID- 16950539
TI  - Characterization of a highly virulent feline calicivirus and attenuation of this
      virus.
AB  - Feline calicivirus (FCV) is a common cause of upper respiratory and oral disease
      in cats. Highly virulent, systemic strains of FCV (vs FCV) have been recently
      described. These vs FCV isolates cause edema, cutaneous ulcers and high mortality
      in affected cats. This study reports a disease model with such a vs FCV isolate
      (FCV-33585). It also describes a full-length capsid gene sequence of this vs FCV
      isolate and the capsid sequence comparison of this strain with 35 other virulent
      and non-virulent FCV strains. In addition, sequence comparison of this strain
      with other 114 known sequences in the hyper-variable region of capsid gene was
      analyzed. Two amino acids were identified within the hyper-variable region as
      potentially unique signature for this vs FCV strain. This study also describes
      the attenuation of FCV-33585 by two methods: serial passaging at low temperature,
      and the generation of a temperature sensitive (ts) mutant by UV irridiation.
      Moreover, the potential use of attenuated vs FCV as vaccine was also explored.
      Monoclonal antibodies were also identified which could differentiate commonly
      used FCV vaccine strain from this vs strain (FCV-33585). And two monoclonal
      antibodies were found to react specifically the wild-type, not the attenuated FCV
      33585.

PMID- 16950540
TI  - Preconception care of women attending adult general diabetes clinics--are we
      doing enough?
AB  - BACKGROUND: The presence of diabetes in pregnancy can result in substantial
      morbidity to both mother and baby if management is sub-optimal. AIMS: To assess
      the process of standards of preconception care (against the National Service
      Framework standards) of women attending the adult general diabetes clinics in a
      district general hospital. METHODS: Retrospective review of case notes of women
      aged 18-40 years attending the general diabetes clinics for annual review, over a
      period of 6 months. RESULTS: Seventy sets of notes were reviewed. The mean age of
      the patients was 32 years. Fifty-six patients had type-1 diabetes and 14 patients
      had type-2 diabetes. Mean duration of diabetes was 13 years. Eighty-six percent
      of the patients had blood pressure recordings documented. Mean blood pressure was
      124/74 mmHg. Mean HbA1c was 9.1%. Documented evidence of home blood glucose
      monitoring was seen in 66% of the patients. Preconception
      counselling/contraception were discussed in 17 patients (25%). Twenty-nine
      patients (41%) were on potentially teratogenic medications. Alcohol and smoking
      history was not documented in 91% and 61% of the patients, respectively.
      CONCLUSIONS: This retrospective assessment highlights that reproductive issues in
      an at risk population of women with diabetes are not included in routine
      management of diabetes care in outpatient clinics.

PMID- 16950541
TI  - Public awareness of the metabolic syndrome.

PMID- 16950542
TI  - Risk factors for long-term complications in patients with type 2 diabetes
      attending government institutions in the Western Province of Sri Lanka: a case
      control study.

PMID- 16950543
TI  - Multi-country study on the prevalence and clinical features of peripheral
      arterial disease in Asian type 2 diabetes patients at high risk of
      atherosclerosis.
AB  - OBJECTIVE: PAD-SEARCH was the first international study to investigate the
      prevalence of peripheral arterial disease (PAD) in Asian type 2 diabetic patients
      and to demonstrate the relationships between putative risk factors and PAD.
      SUBJECTS AND METHODS: In total 6625 type 2 diabetic patients aged 50 and older
      were enrolled and determined ankle-brachial index (ABI) and brachial-ankle pulse
      wave velocity (baPWV) in Korea, China, Taiwan, Hong Kong, Indonesia, Thailand and
      the Philippines. RESULTS: Mean patient age was 63.7+/-8.2 years and mean duration
      of diabetes was 10.3+/-8.0 years. One thousand one hundred and seventy-two
      (17.7%) subjects were diagnosed as PAD by ABI (< or =0.9). PAD subjects had a
      significantly longer duration of diabetes, hypertension, higher HbA1c, and a
      significantly lower mean BMI than non-PAD subjects. In terms of lipid profiles,
      triglyceride was the only significant variable. Notably, mean ABI and baPWV in
      females were significantly poorer than age matched males in subjects with a
      normal ABI. However, mean ABI and baPWV in males were significantly poorer than
      in age matched females in subjects with PAD. CONCLUSIONS: These findings suggest
      that PAD is a common complication in Asian type 2 diabetic patients. Therefore,
      PAD screening and treatment should be emphasized for Asian diabetic patients with
      high risk factors.

PMID- 16950544
TI  - Amylin S20G mutation in Mexican population.
AB  - Diabetes Mellitus type 2 (DM2) is a group of metabolic disorders characterized by
      defective insulin action or secretion or both with a 10.6% incidence in Mexican
      Mestizo population, DM2 is also classified within the localized misfolding
      diseases due to the amyloid pancreatic deposits found in 90% of the DM2
      necropsies. The pancreatic amyloid main component is a protein known as human
      islet amyloid polypeptide (hIAPP) or amylin, the most common mutation is the S20G
      in Asian population with a polymorphic frequency in DM2 Asian patients. The aim
      of this study was to search this mutation in Mexican Mestizo general population
      (104) and DM2 patients (100). This is the first molecular study of hIAPP gene in
      Mexican population and in which we developed an alternative more effective
      antisense primer for the analysis of the NFGAILSS region in hIAPP exon 3 critical
      for the amyloid beta structure formation. We did not find the mutation in any of
      the 204 analyzed samples, thus the findings show that S20G is not a common
      mutation in Mexican Mestizo population.

PMID- 16950545
TI  - Up-regulation of neuropeptide Y Y4 receptor mRNA expression in the brainstem of
      refed rats following 48 h of food deprivation: effect of leptin.
AB  - Neuropeptide Y (NPY) Y4 receptor (Y4R) in rat brainstem has been implicated in
      the signaling of satiety. In this study, we investigated the effects of leptin,
      and refeeding-induced satiety on Y4R mRNA expression in rat brainstem. Y4R
      receptor-specific primers were used to amplify the mRNA obtained from
      hypothalamus and brainstem utilizing conventional RT-PCR and quantitative real
      time RT-PCR. No PCR product for Y4R was obtained from entire hypothalamic mRNA.
      Real-time RT-PCR showed a significant two-fold increase in the relative quantity
      of Y4R mRNA in brainstem of refed rats in comparison to food deprived or ad lib
      fed rats. Consistently, plasma leptin level was elevated in refed rats in
      comparison to food deprived rats. Similarly, leptin-treated rats exhibited a
      significant increase in Y4R mRNA in brainstem as compared to saline-injected
      rats. Plasma leptin was significantly elevated in leptin-treated rats. These
      results suggest that refeeding stimulates the expression of Y4R gene in the
      brainstem and that leptin may be one of the peripheral factors involved in this
      anorectic signaling mechanism.

PMID- 16950546
TI  - Food choice, socio-economic characteristics and health in 4-year olds in a well
      educated urban Swedish community.
AB  - BACKGROUND AND AIMS: Dietary habits founded early in life might influence
      development of welfare diseases. The aim was to analyse food choice, socio
      economic characteristics and health by questionnaires in healthy 4-year olds.
      METHODS: Two hundred and thirty children were invited and 79% completed all
      questionnaires. Anthropometry was measured in 131 subjects. RESULTS: The sample
      was characteristic for Swedish children except that more parents had university
      education. Most children attended pre-school; 52% >30 h/week. Almost all had been
      breast-fed until a mean age of 5 months. Fifteen per cent were overweight and 2%
      obese according to the IOTF cut-offs. A, D vitamin supplementation was not given
      to a third. Full fat dairy products, minced meat and sausages predominated, and
      only a fourth was served fat fish. Olive or rape seed oil was consumed regularly
      by 40% and a third consumed "junk food" regularly. Maternal immigrant status
      influenced the food choice. CONCLUSION: In a Swedish urban community of 4-year
      olds, 17% were overweight or obese. The intake of vegetables, oils and "junk
      food" seemed to have increased, while the intake of dairy products, fruit, meat
      and fish seemed to be similar to earlier studies. Food choice was influenced by
      maternal origin.

PMID- 16950547
TI  - Ginsenoside Rd elicits Th1 and Th2 immune responses to ovalbumin in mice.
AB  - Ginsenoside Rd (Rd), a saponin isolated from the roots of panax notoginseng, was
      evaluated for inducing Th1 or Th2 immune responses in mice against ovalbumin
      (OVA). ICR mice were immunized subcutaneously with OVA 100 microg alone or with
      OVA 100 microg dissolved in saline containing alum (200 microg), or Rd (10, 25 or
      50 microg) on days 1 and 15. Two weeks later (day 28), concanavalin A (Con A)-,
      lipopolysaccharide (LPS)- and OVA-stimulated splenocyte proliferation was
      determined using MTT assay, and OVA-specific antibody titers and levels of
      cytokines in serum were measured by ELISA and microparticle-based flow cytometric
      immunoassay, as well as peripheral blood T-lymphocyte subsets analyzed using flow
      cytometer. Rd significantly enhanced the Con A-, LPS-, and OVA-induced splenocyte
      proliferation in the OVA-immunized mice. OVA-specific IgG, IgG1, and IgG2b
      antibody titers in serum were significantly enhanced by Rd compared with OVA
      control group. Meanwhile, Rd also significantly promoted the production of the
      Th1 and Th2 cytokines in OVA-immunized mice. Further, the effects of Rd on
      expression of cytokine mRNA in Con A-stimulated mice splenocytes were evaluated
      by RT-PCR analysis. Rd significantly enhanced the interleukin-2 (IL-2),
      interferon-gamma (IFN-gamma), IL-4, and IL-10 mRNA expression in mice splenocyte
      induced by Con A. These results suggested that Rd had immunological adjuvant
      activity, and elicited a Th1 and Th2 immune response by regulating production and
      gene expression of Th1 cytokines and Th2 cytokines.

PMID- 16950548
TI  - Comparative efficacy of modified vaccinia Ankara (MVA) as a potential replacement
      smallpox vaccine.
AB  - International concern over the potential consequences of a Bioterrorist or
      Biowarfare associated release of variola virus have prompted renewed interest in
      the vaccines for smallpox. The traditional live, replicating vaccine strains are
      subject to novel safety concerns associated with historical production methods in
      domesticated ruminants and the additional hazards that vaccinia virus poses for
      people with immune system abnormalities or a history of eczematous skin
      conditions. In this study we have examined the longevity and efficacy of immunity
      induced by a non-replicating smallpox vaccine candidate, modified vaccinia Ankara
      (MVA) in a murine model using intranasal and aerosol routes of infection. Two
      step vaccinations of MVA followed by traditional Lister vaccine are compared with
      either Lister alone or MVA alone, and the longevity of the protection induced by
      MVA is assessed. MVA is found to be broadly similar to Lister. Although
      protection is shown to decay with time, when administered at a standard human
      dose the longevity of protection induced by MVA is comparable to that induced by
      Lister.

PMID- 16950549
TI  - Massive hand crush: the role of a free muscle flap to obliterate the dead space
      and to clear deep infection.
AB  - Death of tissue and/or deep infection leading to amputation is not an uncommon
      course of events after massive crush injuries of the central part of the hand.
      Management of this injury faces the dual problem of having to carry out
      debridement in the central part of the hand which is radical enough to remove all
      dead tissue but which, in itself, creates a huge dead space in the depths of the
      wound. Inadequate debridement and/or leaving a dead space which fills with fluid
      and detritus behind the flexor tendons leads on to infection, devascularisation
      of the fingers and amputation. This paper presents the results of very radical
      debridement of the hand dorsal to the flexor tendons, including the
      intermetacarpal spaces, and filling the dead space with a well-vascularised free
      muscle flap in two hands which were referred in a pre-amputation stage, with one
      already being infected. Both hands were salvaged.

PMID- 16950550
TI  - Residual concentrations of micropollutants in benthic mussels in the coastal
      areas of Bohai Sea, North China.
AB  - Studies of heavy metals and organic pollutants in different benthic mussel
      species from Bohai Sea show that concentrations of Cd in mussels commonly exceed
      national biological quality standards. In addition, a site located in Laizhou Bay
      exhibits higher average concentrations of As, Hg and Pb with respect to the other
      sites. Residual levels of petroleum hydrocarbons at several sites in Liaodong Bay
      also exceed quality guidelines. Contents and compositional characteristics of DDT
      and its metabolites in mussels suggest the probability of recent inputs and
      potential ecological risks to the local benthic environment.

PMID- 16950551
TI  - Valence specific laterality effects in prosody: expectancy account and the
      effects of morphed prosody and stimulus lead.
AB  - The majority of studies have demonstrated a right hemisphere (RH) advantage for
      the perception of emotions. Other studies have found that the involvement of each
      hemisphere is valence specific, with the RH better at perceiving negative
      emotions and the LH better at perceiving positive emotions [Reuter-Lorenz, P., &
      Davidson, R.J. (1981) Differential contributions of the 2 cerebral hemispheres to
      the perception of happy and sad faces. Neuropsychologia, 19, 609-613]. To account
      for valence laterality effects in emotion perception we propose an 'expectancy'
      hypothesis which suggests that valence effects are obtained when the top-down
      expectancy to perceive an emotion outweighs the strength of bottom-up perceptual
      information enabling the discrimination of an emotion. A dichotic listening task
      was used to examine alternative explanations of valence effects in emotion
      perception. Emotional sentences (spoken in a happy or sad tone of voice), and
      morphed-happy and morphed-sad sentences (which blended a neutral version of the
      sentence with the pitch of the emotion sentence) were paired with neutral
      versions of each sentence and presented dichotically. A control condition was
      also used, consisting of two identical neutral sentences presented dichotically,
      with one channel arriving before the other by 7 ms. In support of the RH
      hypothesis there was a left ear advantage for the perception of sad and happy
      emotional sentences. However, morphed sentences showed no ear advantage,
      suggesting that the RH is specialised for the perception of genuine emotions and
      that a laterality effect may be a useful tool for the detection of fake emotion.
      Finally, for the control condition we obtained an interaction between the
      expected emotion and the effect of ear lead. Participants tended to select the
      ear that received the sentence first, when they expected a 'sad' sentence, but
      not when they expected a 'happy' sentence. The results are discussed in relation
      to the different theoretical explanations of valence laterality effects in
      emotion perception.

PMID- 16950552
TI  - Seizure following sudden zolpidem withdrawal.
AB  - Zolpidem is a short acting hypnotic drug belonging to imidazopyridine family. It
      produces its hypnotic effects via the GABA-A benzodiazepine receptor complex, and
      binds preferentially to those receptors containing the alpha-1 subunit. In
      comparison with benzodiazepines this mechanism is thought to reduce liability to
      induce dependence. Several case reports of zolpidem abuse and dependence have
      been published along with a small number of cases demonstrating seizures after
      sudden zolpidem withdrawal. We describe a case of a 29-year-old Caucasian woman
      who developed a generalized seizure following sudden zolpidem withdrawal
      subsequent to drug dependence to 160mg of zolpidem. The clinical effects of
      zolpidem seem to be comparable to those of benzodiazepines and abuse, dependence
      and withdrawal seizures belong to the spectrum of its adverse drug reactions.

PMID- 16950553
TI  - Effects of the Fusarium toxin deoxynivalenol from naturally contaminated wheat
      given subchronically or as one single dose on the in vivo protein synthesis of
      peripheral blood lymphocytes and plasma proteins in the pig.
AB  - Trichothecenes, such as deoxynivalenol (DON), are known to inhibit the protein
      synthesis in vitro by binding at the 60S subunit of eukaryotic ribosomes.
      Therefore, cells and tissues with high protein turnover, such as lymphocytes and
      the liver (albumin and fibrinogen synthesis), were suggested to react most
      sensitively to DON. However, to the author's knowledge this observation was not
      proven in vivo in pigs, which were regarded as the farm animals most susceptible
      to DON. A total of 31 castrated male, crossbred German Landrace x Pietrain pigs
      weighing approx. 40 kg were fed a DON contaminated diet (5.7 mg/kg) either
      acutely (one single dose) or subchronically (4 weeks) or a control diet (0.1
      mg/kg). In addition, one group received an intravenous injection of 53 microg
      DON/kg LW. One hour after feeding, a "flooding dose" of the stable isotope l
      [(2)H(5)]-phenylalanine (125 mg/kg LW) was given and frequent blood samples
      (permanent catheter) were collected over a 60 min period. The molar percent
      excess (MPE) of plasma free and protein-bound phenylalanine were measured by
      GC/MS. No differences could be observed in the plasma concentrations of total
      protein, albumin, fibrinogen and serum enzymes between the groups. On the other
      hand, fractional synthesis rates (FSR, %/d) of albumin were significantly
      decreased by 43%, 45% and 26% and FSR of lymphocytes declined by 27%, 19% and
      24%, whereas fibrinogen was not significantly affected after subchronic or one
      single oral and intravenous DON exposure, respectively. Additionally, the
      absolute synthesis rate (ASR, g/d) of albumin and the proportion of albumin to
      total body protein synthesis were reduced in the same manner, whereas the albumin
      secretion time ranged between 6.8 and 34.4 min and was not affected by treatment.
      In conclusion, the flooding dose technique appeared to be suitable for
      distinguishing DON-related effects on the protein synthesis, while determination
      of plasma protein concentrations seemed not to be an appropriate parameter.

PMID- 16950554
TI  - Oral administration of yessotoxin stabilizes E-cadherin in mouse colon.
AB  - YTX has been shown to disrupt the E-cadherin-catenin system in cultured
      epithelial cells, raising some concern that ingestion of seafood contaminated by
      YTX might favour tumour spreading and metastasis formation in vivo. In order to
      probe whether YTX might affect cadherin systems in vivo, we have set up a study
      involving repeated oral dosing of the toxin in mice (1mg/kg/day, for 7 days) and
      analysis of E-cadherin and N-cadherin in tissue extracts obtained at the end of
      the dosing scheme, as well as 1 and 3 months after YTX administration. We found
      that the E-cadherin pools obtained from lung and kidney were not altered by YTX
      in any of our experimental conditions. Extracts from mouse colon contained intact
      E-cadherin and an E-cadherin fragment of about 90 kDa (ECRA(90)), displaying a
      molecular alteration resembling that caused by YTX in cultured cells. We found
      that the relative proportion of ECRA(90), as compared to intact E-cadherin, was
      higher in colon extracts from control mice than from YTX-treated animals,
      indicating that oral administration of YTX to mice stabilizes E-cadherin of mouse
      colon. No significant difference could be detected in samples prepared from
      colons obtained 30 or 90 days after termination of YTX treatment. Oral
      administration of YTX to mice did not lead to a significant increase in the
      fragments of E-cadherin detectable in serum, neither it altered the N-cadherin
      pool of mouse heart. Electron microscopy analysis showed no substantial
      ultrastructural differences between controls and YTX-treated mice. Our findings
      show that ingestion of food contaminated by YTX poses a low risk of disruption of
      the E-cadherin system in vivo.

PMID- 16950555
TI  - Resistance to degradation of resin-dentin bonds using a one-step HEMA-free
      adhesive.
AB  - OBJECTIVE: To evaluate the resistance to degradation of resin-dentin bonds formed
      with a one-step acetone-containing and HEMA-free adhesive. METHODS: Flat, mid
      coronal dentin surfaces were bonded with G Bond under dry and wet conditions. The
      bonded teeth were subjected to fatigue loading (90 or 250 N) using 5000 or 50000
      cycles (at 3.0 Hz) and to chemical degradation (10% NaOCl immersion for 5 h).
      Specimens were sectioned into beams and tested for microtensile bond strength.
      Fractographic analysis was performed by scanning electron microscopy (SEM).
      Additional specimens were processed for morphological examination of the
      interfaces. RESULTS: Bond strength significantly decreased after the chemical
      challenge (p<0.05), but not after load cycling. Dentinal moisture did not affect
      bond strength. Most of the recorded failures were adhesive and located at the top
      of the hybrid layer. A poorly infiltrated hybrid layer with bubbles entrapped
      within the adhesive was observed in all groups. CONCLUSIONS: A discrepancy
      between water/solvent evaporation rate and convective and evaporative water
      fluxes from the underlying dentin may be responsible of the droplet formation
      within the adhesive layer, thus reducing bond strength. A "stress relieving"
      effect may occur during loading. A loss of bonding effectiveness is expected
      overtime, mainly due to chemical degradation of the hybrid layer.

PMID- 16950556
TI  - A novel fibrinolytic serine protease from the polychaete Nereis (Neanthes) virens
      (Sars): purification and characterization.
AB  - A novel fibrinolytic serine protease has been identified and purified to
      homogeneity from the coelomic fluid of polychaete Nereis (Neanthes) virens
      (Sars), and named N-V protease. N-V protease is a 29kDa single chain protein with
      an isoelectric point of pH 4.5. It hydrolyzes Aalpha-chain of fibrinogen with a
      high efficiency, and the Bbeta- and gamma-chains (Aalpha>Bbeta>gamma) with a
      lower efficiency. The proteolytic activity peaks at pH 7.8 is 45 degrees C. The
      activity is completely inhibited by serine protease inhibitors DFP (I(50)=5.8 x
      10(-4)M) and PMSF (I(50)=5.5 x 10(-2)M), and almost completely by TLCK (I(50)=7.7
      x 10(-1) M). But aprotinin, elastinal, SBTI, benzamidine, PCMB, EDTA, EGTA,
      iodoacetate, E64, and beta-mercaptoethanol have no effect on the protease
      activity. Therefore, N-V protease is identified as a serine protease. The primary
      amino acid sequence of N-V protease was determined by mass spectrometry (N-V
      protease, No. P83433). According to the MALDI-TOF MS analysis, there is no
      existing protein in the NCBI Non-redundant Protein Sequence Database that matches
      the N-V protease sequence. Therefore, N-V protease is a novel and special protein
      in N. virens. Furthermore, we have successfully established an expression cDNA
      library from the whole body of N. virens (data not shown).

PMID- 16950557
TI  - Effects of social anxiety and evaluative threat on cardiovascular responses to
      active performance situations.
AB  - This study investigated the joint influence of trait social anxiety and
      evaluative threat on psychological and cardiovascular responses to active coping
      situations. Fifty-two normotensive female students characterized as either high
      or low in trait social anxiety performed a mental arithmetic task and a speech
      task requiring persuasive behavior in a context of high or low evaluative threat.
      Trait social anxiety exerted a substantial influence on cardiovascular
      reactivity. High socially anxious individuals overall exhibited greater heart
      rate reactivity. For systolic and diastolic blood pressure enhanced reactivity of
      socially anxious individuals was confined to low evaluative threat. At high
      levels of evaluative threat no group differences were observed due to somewhat
      attenuated reactivity in high compared to low socially anxious individuals.
      Cognitive appraisals and affective arousal were not found to mediate the effects
      of social anxiety on cardiovascular reactivity. Results were attributed to
      differences in effort expenditure rather than experienced anxiety.

PMID- 16950558
TI  - Cardiovascular health among children born after assisted reproduction.

PMID- 16950559
TI  - Pelvic exenteration for primary and recurrent gynaecological malignancies.
AB  - OBJECTIVE: Analyse the outcome of pelvic exenteration for gynaecological
      malignancies in a tertiary referral center. Post-operative in-hospital morbidity,
      long-term morbidity, disease free and overall survival rates were studied. STUDY
      DESIGN: Between 1991 and 2004, 42 patients underwent an anterior, total or
      posterior exenteration for gynaecological malignancies. Follow-up was obtained
      from patient files; disease free and overall survival were calculated and
      prognostic factors were studied. RESULTS: A pelvic exenteration was performed in
      14 patients for primary and 28 patients for recurrent gynaecological cancers. In
      hospital complications occurred in 19 patients (45%) of whom seven patients
      needed a reoperation (17%). Late complications occurred in 31 patients (75%); 21
      reinterventions were performed (50%). Five-year disease free and overall survival
      was, respectively, 48 and 52%. Age, type of surgery, histology, localisation of
      the tumour, lateral wall involvement, completeness of resection and primary
      versus recurrent cancer were not identified as prognostic factors for recurrence
      or survival. CONCLUSION: Long-term survival is possible in about 50% of patients
      after pelvic exenteration for gynaecological cancers, but is associated with
      significant post-operative morbidity.

PMID- 16950560
TI  - Gene therapy for erectile dysfunction: fact or fiction?
AB  - OBJECTIVES: Erectile dysfunction (ED) is a major health problem that seriously
      affects the quality of life of patients and their partners. Although all three
      selective phosphodiesterase type 5 inhibitors (PDE5-Is) are effective in the
      majority of ED cases, PDE5-I therapy is less efficacious in some hard-to-treat
      populations (diabetics, men after radical prostatectomy), prompting the
      development of new approaches, including gene therapy strategies for ED. METHODS:
      Gene therapy approaches are discussed in terms of the possible role of gene
      therapy for the treatment of ED, potential targets for gene transfer, vectors to
      carry targeted genes, and gene strategies for ED in certain disease states, such
      as diabetes, ageing, arterial and venogenic insufficiency, and cavernous nerve
      injury. RESULTS: The penis is a convenient tissue target for gene therapy because
      of its external location and accessibility, the ubiquity of endothelial-lined
      spaces, and low level of blood flow, especially in the flaccid state. Gene
      therapy approaches have focused on a number of signaling pathways that are
      crucial for penile erection, such as nitric oxide/cyclic guanosine monophosphate,
      RhoA/Rho-kinase, growth factors, ion channels, peptides, and control of oxidative
      stress. CONCLUSIONS: The need for effective ED therapies in difficult-to-treat
      patients has encouraged investigators to seek novel modalities for the treatment
      of ED. Recent preclinical and clinical trials have demonstrated that gene therapy
      strategies may be feasible for these purposes.

PMID- 16950561
TI  - Aberrant crypt foci in patients with a positive family history of sporadic
      colorectal cancer.
AB  - Early detection is crucial in the prevention of colorectal cancer (CRC) deaths.
      The earliest detectable neoplastic lesion in the colon is the aberrant crypt foci
      (ACF). A major question is whether ACF are precursors of CRC, and thus, early
      biomarkers for CRC risk. If so, we hypothesized that the number of ACF would be
      higher in patients who had a family history of CRC compared to patients without.
      We counted ACF in the distal 20cm of colon/rectum during 103 colonoscopic
      examinations using a prototype Close Focus Colonoscope (Olympus Corp.) with
      methylene blue chromendoscopy. Each patient was asked whether they had a family
      history of CRC in a first degree relative, or a personal history of CRC or
      adenoma. Patients answering 'no' to these questions (n=17) had a mean number of
      ACF of 4.4; the mean was significantly higher in the patients with a positive
      family history of CRC (9.0, p<0.01; n=43) or a personal history of advanced
      adenoma (7.5, p<0.05; n=34).

PMID- 16950562
TI  - Defective acute apoptotic response to genotoxic carcinogen in small intestine of
      APC(Min/+) mice is restored by sulindac.
AB  - The effect of APC loss on azoxymethane (AOM)-induced apoptosis and cell
      proliferation, as well as their regulation by sulindac was examined in colon and
      small intestine in APC(Min/+) mice. APC(Min/+) mice showed increased epithelial
      proliferation in all regions, with significant impairment of apoptosis in small
      intestine, but not in colon. Sulindac administration restored defective apoptosis
      to normal. As the apoptotic defect occurred at the major site of intestinal tumor
      formation in APC(Min/+) mice and as it was restored to normal by a proven
      chemopreventive agent, this defect in apoptosis might be a key biological
      consequence of APC dysfunction contributing to tumor formation.

PMID- 16950563
TI  - Telomerase targeted anticancer bioactive prodrug by antisense-based approach.
AB  - A deoxy 11-mer oligonucleotide 5'-GTTAGGGTTAG-3', complementary to a repeat
      sequence of human telomerase RNA template has been linked through phosphate and a
      C-2 linker to a bioactive tetraglycine conjugate of curcumin, a well-known
      antitumor herbal spice component of turmeric. This molecule has been transfected
      into KB and HeLa cell lines and found to affect cell growth in the former. This
      DNA-curcumin-tetraglycine acts as a prodrug being targeted by antisense mechanism
      to telomerase.

PMID- 16950564
TI  - Toxicity studies in a chemical dye production industry in Turkey.
AB  - This study investigated the acute toxicity of chemical dye production industry
      wastewaters by traditional and enrichment toxicity tests and emphasized the
      importance of toxicity tests in wastewater discharge regulations. The enrichment
      toxicity tests are novel applications indicating whether there is potential
      toxicity or stimulation conditions. Different organisms were used including
      bacteria (floc-Zoogloea ramigera and coliform-Escherichia coli bacteria), algae
      (Chlorella vulgaris), fish (lepistes-Poecilia reticulate) and protozoan
      (Vorticella campanula) to represent four tropic levels. The toxicity test results
      were compared with chemical analyses to identify the pollutants responsible for
      the toxicity in the effluent wastewater samples. Toxicity of the effluents could
      not be explained by using physicochemical analyses in four cases. The results
      clearly showed that the use of bioassay tests produce additional information
      about the toxicity potential of industrial discharges and effluents.

PMID- 16950565
TI  - Photocatalytic degradation of C.I. Acid Red 27 by immobilized ZnO on glass plates
      in continuous-mode.
AB  - The photocatalytic degradation of C.I. Acid Red 27 (AR27), an anionic monoazo dye
      of acid class, in aqueous solutions was investigated with immobilized ZnO
      catalyst on glass plates in a continuous-mode. In the slurry ZnO system the
      separation and recycling of the photocatalyst is practically difficult. Thus, ZnO
      was immobilized on solid supports to solve this problem. The removal percent
      increases with increasing the photoreactor volume and light intensity but it
      decreases when the flow rate is increased. With decreasing flow rate from 43 to
      15mlmin(-1), the complete decolorization and degradation was obtained at around
      748 and 1080cm(3) from photoreactor volume. The increase in the light intensity
      from 21.4 to 58.5Wm(-2) increases the decolorization from 23 to 57.6% and
      degradation from 17.5 to 37.8% for 374cm(3) of photoreactor volume. NH(4)(+),
      NO(3)(-), NO(2)(-) and SO(4)(2-) ions were analyzed as mineralization products of
      nitrogen and sulfur heteroatoms. Results showed that final concentration of
      SO(4)(2-) ions and N-containing mineralization products were less than the
      finally expected stoichiometric values. The positive slope of production of
      NH(4)(+), NO(3)(-) and NO(2)(-) shows that these compounds are initial products
      resulting directly from the initial attack on the nitrogen-to-nitrogen double
      bond (-NN-) of the azo dye.

PMID- 16950566
TI  - Measurement of minimum ignition energies of dust clouds in the <1mJ region.
AB  - The lower energy limit of current standard test apparatus for determining the
      minimum ignition energy (MIE) of dust clouds is in the range of 1-3mJ. This is a
      quite severe limitation because many dusts ignite readily at this energy level. A
      new spark generator, capable of producing synchronised sparks of very low
      energies and with an integrated system for measurement of spark energy, has
      therefore been developed and employed to a number of easily ignitable dusts.
      Before testing the MIE of dust clouds, it was considered essential to calibrate
      the new spark generator against a gas of known MIE. For this purpose, a mixture
      of propane and air was selected. However, a comprehensive literature review
      revealed that the reported MIEs of this gas mixture vary significantly, depending
      on the spark discharge characteristics, including discharge duration. When taking
      these factors into account, it was concluded that the new spark generator yielded
      reasonable results for propane/air. Applying the new spark generator to explosive
      dust clouds showed that a number of dusts do in fact have MIEs that are one to
      two orders of magnitude lower than 1mJ. The new spark generator may therefore
      offer a basis for developing a standard test apparatus in the low-energy region.
      When using a method of triggering the spark by the explosive dust cloud itself,
      which probably is a more industrially relevant process than synchronisation
      between the dust dispersion and sparkover, somewhat higher MIEs were found
      compared to those determined when using synchronised sparks. However, even with
      this method of spark triggering, MIEs below 1mJ were found.

PMID- 16950567
TI  - Batch kinetics and isotherms for biosorption of copper(II) ions onto pre-treated
      powdered waste sludge (PWS).
AB  - Waste sludge samples from different plants were tested for Cu(II) ion biosorption
      capacities with and without pre-treatment. Waste sludge from a paint industry
      wastewater treatment plant was found to perform better than the others after pre
      treatment with 1% H(2)O(2). Powdered waste sludge (PWS) from the paint industry
      wastewater treatment plant was used for recovery of Cu(II) ions from aqueous
      solution by biosorption after pre-treatment with 1% H(2)O(2). Batch kinetics and
      isotherms of biosorption of Cu(II) ions were investigated at variable initial
      Cu(II) concentrations between 50 and 400 mg l(-1) with a PWS particle size of 64
      microm. The pseudo-first and -second order kinetic models were used to correlate
      the experimental data. The kinetic constants were determined for both models and
      the second order kinetic model was found to be more suitable. The Langmuir,
      Freundlich and the generalized isotherm models were used to correlate the
      equilibrium biosorption data and the isotherm constants were determined. The
      Langmuir isotherm was found to fit the experimental data better than the other
      isotherms tested. The maximum biosorption capacity (116 mg g(-1)) of the pre
      treated powdered waste sludge for Cu(II) ions was found to be superior as
      compared to the other biosorbents reported in literature.

PMID- 16950568
TI  - Environmental stress-corrosion cracking of fiberglass: lessons learned from
      failures in the chemical industry.
AB  - Fiberglass reinforced plastic (FRP) composite materials are often used to
      construct tanks, piping, scrubbers, beams, grating, and other components for use
      in corrosive environments. While FRP typically offers superior and cost effective
      corrosion resistance relative to other construction materials, the glass fibers
      traditionally used to provide the structural strength of the FRP can be
      susceptible to attack by the corrosive environment. The structural integrity of
      traditional FRP components in corrosive environments is usually dependent on the
      integrity of a corrosion-resistant barrier, such as a resin-rich layer containing
      corrosion resistant glass fibers. Without adequate protection, FRP components can
      fail under loads well below their design by an environmental stress-corrosion
      cracking (ESCC) mechanism when simultaneously exposed to mechanical stress and a
      corrosive chemical environment. Failure of these components can result in
      significant releases of hazardous substances into plants and the environment. In
      this paper, we present two case studies where fiberglass components failed due to
      ESCC at small chemical manufacturing facilities. As is often typical, the small
      chemical manufacturing facilities relied largely on FRP component suppliers to
      determine materials appropriate for the specific process environment and to
      repair damaged in-service components. We discuss the lessons learned from these
      incidents and precautions companies should take when interfacing with suppliers
      and other parties during the specification, design, construction, and repair of
      FRP components in order to prevent similar failures and chemical releases from
      occurring in the future.

PMID- 16950569
TI  - Preparation and evaluation of cerium(IV) tungstate powder as inorganic exchanger
      in sorption of cobalt and europium ions from aqueous solutions.
AB  - Cerium(IV) tungstate powder was chemically synthesized and exploited as adsorbent
      material for the decontamination study of cobalt and europium ions from
      radioactive waste solutions under simulated conditions using batch technique. The
      influences of pH, particle size and temperature have been reported. The uptake of
      europium was found to be slightly greater than that of cobalt and the apparent
      sorption capacity increases with increase in temperature. Thermodynamic
      parameters such as changes in Gibbs free energy (DeltaG degrees), enthalpy
      (DeltaH degrees), and entropy (DeltaS degrees) were calculated. The numerical
      value of DeltaG degrees decreases with an increase in temperature, indicating
      that the sorption reaction of each ion was spontaneous and more favorable at
      higher temperature. The positive values of DeltaH degrees correspond to the
      endothermic nature of sorption processes and suggested that chemisorption was the
      predominant mechanism. A comparison of kinetic models applied to the sorption
      rate data of each ion was evaluated for the pseudo first-order, the pseudo second
      order, intraparticle diffusion and homogeneous particle diffusion kinetic models.
      The results showed that both the pseudo second-order and the homogeneous particle
      diffusion models were found to best correlate the experimental rate data. The
      numerical values of the rate constants and particle diffusion coefficients were
      determined from the graphical representation of the proposed models. Activation
      energy (E(a)) and entropy (DeltaS++) of activation were also computed from the
      linearized form of Arrhenius equation.

PMID- 16950570
TI  - Psychosocial factors associated with pain intensity, pain-related interference,
      and psychological functioning in persons with multiple sclerosis and pain.
AB  - Biopsychosocial models of chronic pain that recognize psychological and
      environmental factors as important aspects of adjustment to pain have been
      proposed for understanding chronic pain and related suffering in persons with
      multiple sclerosis (MS), but such models have not been empirically tested. The
      objective of this study was to test such a model by evaluating the associations
      of several psychosocial variables (i.e., pain-related catastrophizing, perceived
      social support, pain beliefs, and pain coping) with pain intensity, pain
      interference with functioning, and psychological functioning in persons with
      chronic pain and MS, after controlling for demographic and disease-related
      factors. Participants were 125 community-dwelling persons with MS and pain who
      completed a mailed questionnaire that included measures of pain intensity and
      interference, psychological functioning, catastrophizing, social support, and
      pain beliefs and coping. The psychosocial variables accounted for an additional
      25% of the variance in average pain intensity after controlling for demographic
      and disease-related variables (p<.001). These variables explained an additional
      22% of the variance in pain-related interference (p<.001) and 43% of the variance
      in psychological functioning (p<.001), after adjusting for demographic and MS
      related variables and average pain intensity. Catastrophizing was consistently
      and independently associated with all criterion measures, whereas social support,
      pain beliefs, and pain coping were associated with some criterion measures but
      not others. The results provide empirical support for a biopsychosocial
      understanding of chronic pain in MS and suggest that specific psychosocial
      factors (e.g., catastrophizing) may be important regarding adjustment to pain in
      persons with MS.

PMID- 16950571
TI  - Medical withdrawal management in Vancouver: service description and evaluation.
AB  - This study evaluates a medically managed inpatient detoxification service
      (Vancouver Detox (VD)) and investigates its clients' characteristics over a 1
      year period. We present information on the daily operation at VD, and examine
      accessibility and efficiency of it from five perspectives: wait time,
      pretreatment attrition rate, treatment completion rate, length of stay (LOS), and
      occupancy rate (OR). In addition, we explore the impacts of seasonality and the
      monthly welfare check on the utilization of the service. Among 2294 referrals,
      35% dropped out without engaging in treatment. Among those who were admitted to
      VD, 78% completed the treatment program. Shorter wait time and lower OR were
      found during the welfare check issuance period, and lower OR was found during
      summer. In addition, the patterns of utilization of VD were changed over the
      welfare check issuance period. Our analysis indicates that operational
      accessibility and efficiency at VD could be improved by specifically addressing
      these factors.

PMID- 16950572
TI  - Readiness to change smoking behavior in adolescents with psychiatric disorders.
AB  - There has been recent increased interest in utilizing motivational interviewing
      (MI) to increase adolescent readiness to quit smoking, but attempts to impact
      quit rates have thus far been discouraging. A better understanding of factors
      associated with adolescent readiness to quit smoking prior to receiving any
      intervention may provide guidance when tailoring future MI interventions in order
      to increase their effectiveness with this population. Adolescent smokers (N=191)
      who had been admitted to a psychiatric hospital and enrolled in a clinical trial
      evaluating MI completed questionnaires that assessed smoking behavior and
      variables thought to be related to smoking. Confidence to quit smoking and
      negative beliefs about smoking were significant predictors of adolescents'
      baseline readiness to quit smoking. The failure to demonstrate relationships
      between health consequences and readiness suggest that caution may be warranted
      in the use of feedback, a common component of MI-based interventions. Such
      feedback tends to focus on health consequences, which was unrelated to adolescent
      baseline readiness to change smoking behavior in the current study. Parallels
      between current results and the Theory of Planned Behavior are discussed in
      consideration of developing more effective MI-based interventions for adolescent
      smokers.

PMID- 16950573
TI  - Non-treatment-seeking heavy drinkers: effects of chronic cigarette smoking on
      brain structure.
AB  - We previously reported [Cardenas, V.A., Studholme, C., Meyerhoff, D.J., Song, E.,
      Weiner, M.W., 2005. Chronic active heavy drinking and family history of problem
      drinking modulate regional brain tissue volumes. Psychiatry Res. 138, 115-130]
      that non-treatment-seeking, active heavy drinkers (HD) demonstrated smaller
      regional neocortical gray matter volumes compared to light drinking controls;
      however, the potential effects of chronic cigarette smoking on regional brain
      volumes were not addressed. The goal of this retrospective analysis was to
      determine if chronic smoking affected brain structure in the non-treatment
      seeking heavy drinking sample from our earlier report (i.e., Cardenas et al.,
      2005). Regional volumetric comparisons were made among age-matched smoking HD
      (n=17), non-smoking HD (n=16), and non-smoking light drinkers (nsLD; n=20) from
      our original sample. Quantitative volumetric measures of neocortical gray matter
      (GM), white matter (WM), subcortical structures, and cerebral spinal fluid (CSF)
      were derived from high-resolution magnetic resonance imaging. Smoking HD
      demonstrated smaller volumes than nsLD in the frontal, parietal, temporal GM, and
      for total neocortical GM. Smoking HD also demonstrated smaller temporal and total
      GM volumes than non-smoking HD. Non-smoking HD and nsLD did not differ
      significantly on GM volumes. Further, the three groups did not differ on lobar
      WM, subcortical structures or regional CSF volumes. These retrospective analyses
      indicate neocortical GM volume reductions in non-treatment-seeking smoking HD,
      but not in non-smoking HD, which are consistent with our studies in recently
      detoxified treatment-seeking alcohol-dependent samples.

PMID- 16950574
TI  - Association of THR105Ile, a functional polymorphism of histamine N
      methyltransferase (HNMT), with alcoholism in German Caucasians.
AB  - BACKGROUND: CNS histamine has been shown to have an inhibitory effect on reward
      and it is implicated in the etiology of addiction and stress. Histamine N
      methyltransferase (HNMT) is believed to be the sole pathway for termination of
      the neurotransmitter action of histamine in mammalian brain. A common, functional
      polymorphism, a C314T transition in the HNMT gene, results in a Thr105Ile
      substitution of the protein encoded. A recent study has shown that the frequency
      of the Ile105 allele was significantly lower in alcoholics compared to that in
      non-alcoholics in Finns and Plains American Indians. Following up these results,
      we tested whether the Thr105Ile polymorphism was associated with alcoholism in
      German Caucasians. METHODS: Thr105Ile was genotyped in n=366 psychiatrically
      interviewed German Caucasian ICD-10 lifetime alcoholics, along with n=200
      ethnically matched controls. RESULTS: No significant difference was found in the
      frequency of the Ile105 allele between alcoholics (0.11) and controls (0.10)
      (chi(2)=0.21, d.f.=1, p=0.647). Likewise, genotype distributions did not differ
      significantly. However, the frequency of the Ile105 allele was significantly
      lower in male alcoholics with a family history of alcoholism compared to that in
      male alcoholics without a family history of alcoholism (chi(2)=4.07, d.f.=1,
      p=0.044). CONCLUSIONS: In German Caucasians the association of the HNMT Thr105Ile
      polymorphism with alcoholism was not replicated per se, but a congruent
      association was found between the Ile105 allele and family history of alcoholism
      supporting the protective role of the Ile105 allele against alcoholism.

PMID- 16950575
TI  - Isolation and molecular characterization of the porcine transforming growth
      factor beta type I receptor (TGFBR1) gene.
AB  - The transforming growth factor beta (TGF beta) family is essential for normal
      growth and development of different organ systems. Here we describe the isolation
      and molecular characterization of the full-length cDNA and the determination of
      the genomic DNA sequence of the porcine TGFBR1 gene. The full-length TGFBR1 cDNA
      1813 bp contains an open reading frame (ORF) of 1512 bp encoding a TGFBR1 protein
      of 503 amino acids with a calculated molecular weight (Mw) of 56.4 kDa. A BAC
      clone harboring the porcine TGFBR1 gene was isolated and sequenced. The results
      of genomic and cDNA sequences of the porcine TGFBR1 gene demonstrated that it
      spans a transcription unit of 62,182 bp consisting of nine exons ranging from 125
      to 354 bp, and eight introns ranging from 1003 to 29,441 bp. A shorter porcine
      TGFBR1 isoform resulting from the alternative splicing of exon 7 in porcine
      TGFBR1 cDNA was detected. The shorter TGFBR1 isoform contained a 1140 bp ORF
      encoding 379 amino acids with a calculated Mw of 41.7 kDa. The core promoter of
      porcine TGFBR1 gene lacks a TATA box but contains GC boxes and CAAT boxes.
      Multiple transcription initiation and termination sites were identified in
      untranslated regions (UTR) resulting in the size of 5'-UTR varying from 15 to 62
      bp, and the length of 3'-UTR varying from 169 to 228 bp. Quantitative real time
      PCR results showed that the TGFBR1 transcript was ubiquitously expressed in all
      tissues examined (i.e. fat, adrenal, brain, spinal cord, muscle, mandibular lymph
      node, thymus, bone marrow, uterus, spleen, testis, kidney, liver, and ovary). A
      total of eighty-five gene polymorphisms (77 SNPs and 8 indels) were detected in
      the porcine TGFBR1 gene by utilizing a panel of DNA from eight diversified pig
      breeds (Yorkshire, Chinese Meishan, Berkshire, Duroc, Hampshire, Landrace, Large
      White and Pietrain). The minor allele frequencies of these nucleotide variations
      varied from 0.13 to 0.5 with an average of 0.26. In addition, seventeen
      microsatellites were identified throughout the genomic sequence of the porcine
      TGFBR1 gene.

PMID- 16950576
TI  - Genomic organization and transcript profiling of the bovine toll-like receptor
      gene cluster TLR6-TLR1-TLR10.
AB  - Toll-like receptors (TLRs) are a family of recognition receptors playing a
      crucial role in the innate immune system. Different combinations of TLRs are
      thought to be crucial for effective immune response, thus insight into the
      organization and expression of TLRs is important for understanding disease
      resistance. Mastitis is the most frequent and costly disease in dairy production,
      and the innate immune system is considered to be important in the first line
      defence against this disease. In the present paper we have characterized the
      genomic organization of TLR6-TLR1-TLR10 in a approximately 50 kb region of bovine
      chromosome 6, including 5'-untranslated exons not previously described. A method
      for gene expression analysis was developed and used for transcription profiling
      of the three paralogous genes in different bovine tissues. The expression
      analysis showed similar expression profiles for TLR1 and TLR6, which indicate a
      co-regulation of these two genes in cattle. TLR10 had a different expression
      profile, pointing toward a stronger functional diversification compared to TLR1
      and TLR6. The differences in expression are in accordance with the evolutionary
      history of this gene cluster, where TLR10 diverged from the common ancestral gene
      before the duplication event that created TLR1 and TLR6.

PMID- 16950577
TI  - Sleep restriction increases blood neutrophils, total cholesterol and low density
      lipoprotein cholesterol in postmenopausal women: A preliminary study.
AB  - OBJECTIVES: This study examines the effects of sleep restricted to 4h for three
      consecutive nights on blood parameters known to be associated with cardiovascular
      risk in healthy postmenopausal women. MATERIAL AND METHODS: Ten healthy
      postmenopausal women aged 55-65 years treated with hormonal replacement therapy
      (HT) were included in the study. After one baseline night, three nights of sleep
      restricted to 4h were performed and were followed by one recovery night of 8h.
      Blood samplings were performed after the baseline night and after the third night
      of sleep restriction. RESULTS: A significant increase in white blood cells (WBC),
      monocytes, neutrophils, total cholesterol, and low density lipoprotein
      cholesterol (LDL-c) was observed after the third night of sleep restriction.
      CONCLUSION: Sleep restriction to 4h of sleep for three consecutive nights
      affected two factors associated with cardiovascular risk in healthy
      postmenopausal women treated with HT.

PMID- 16950578
TI  - AI-700 pharmacokinetics, tissue distribution and exhaled elimination kinetics in
      rats.
AB  - The purpose of these studies was to determine the pharmacokinetics, tissue
      distribution, and exhaled elimination kinetics in rats for intravenously
      administered AI-700, which consists of porous microspheres containing
      decafluorobutane (DFB), for use as an ultrasound contrast agent. [Pd]-AI-700 was
      administered intravenously to rats (10 mg microspheres/kg). Blood and tissue
      samples collected at specified times were analyzed for palladium by inductively
      coupled plasma-mass spectrometry (ICP-MS). AI-700 was also administered
      intravenously to rats (40 mg microspheres/kg) and expired air was collected over
      time. Expired air samples were analyzed for DFB by validated adsorbent trapping
      thermal desorption-gas chromatography-mass spectrometry methodology. Pd from [Pd]
      AI-700 was cleared from blood with a ca. 50-85% decline from peak concentration
      within 5 min. At 1440 min post-dose, 52-72% of the Pd dose was recovered from
      organs of the reticuloendothelial system. Approximately 77% of the intravenously
      injected DFB was found in expired air within 3h after dosing, with most of the
      DFB dose (61+/-6%) expired within the first 10 min after dosing. As expected, the
      microspheres were cleared through the reticuloendothelial system, and the DFB was
      eliminated in expired air, with more than half of the DFB eliminated within the
      first 10 min after dosing.

PMID- 16950579
TI  - Evaluation of an eucalyptus oil containing topical drug delivery system for
      selected steroid hormones.
AB  - In the present study the permeation and the chemical stability of 17-beta
      estradiol, progesterone, cyproterone acetate and finasteride incorporated in an
      eucalyptus oil containing microemulsion system have been investigated. The
      formulations contained 1% (w/w) of the steroid hormones. Self diffusion
      coefficients determined by pulsed-field-gradient spin echo NMR spectroscopy were
      used to characterise the microemulsion. From these results a bicontinuous
      structure is proposed for the multicomponent system. However a correlation
      between the self diffusion of the hormones in the vehicle and the transdermal
      flux was not indicated. Explanations for this were self assembling, formation of
      aggregates between the components of the microemulsion and drugs and different
      effects because of different solubility of the drugs. By addition of certain
      polymers the skin permeation rates could be improved with exception of
      cyproterone acetate. Beside standard diffusion experiments, the residual drug
      content in the skin was investigated. Drug stability was monitored by analysing
      the steroid hormone content in the different formulations over an observation
      period of 6 weeks and could be improved by polymers. In addition, viscosity
      measurements were performed. They indicated an influence of the polymers and
      drugs on the viscosity in all formulations.

PMID- 16950580
TI  - Improvement of the intestinal membrane permeability of low molecular weight
      heparin by complexation with stem bromelain.
AB  - The aim of this study was to investigate the influence of the proteolytic enzyme
      bromelain on the permeation of heparin across the gastrointestinal epithelial
      barrier. Stability of the complex and effect of heparin on the enzymatic activity
      of bromelain was analysed photometrically by measuring bromelain enzymatic
      activity in complex with the heparin. In vitro permeation studies were performed
      with Caco-2 cell monolayer and rat small intestinal mucosa in Ussing-type
      chambers, respectively. Results revealed that enzymatic activity of bromelain
      remained uninfluenced by the immobilization of heparin on it. Transport studies
      across Caco-2 cell monolayer and rat small intestine showed that the permeation
      of heparin could be significantly increased in presence of bromelain. In the
      study with Caco-2 cells, the most effective molar ratio of bromelain to heparin
      was 2:1, leading to 6.7-fold improvement in uptake, whereas the molar ratio 1:1
      showed the highest permeation enhancing effect in the study on intestinal mucosa.
      This study provides evidence that heparin and bromelain form stable complexes
      leading to a significantly improved uptake of heparin.

PMID- 16950581
TI  - RETRACTED: Prevention of hearing loss from noise exposure using Src inhibitors.
AB  - This article has been retracted consistent with Elsevier Policy on Article
      Withdrawal. Please see The Publisher apologizes for any inconvenience this may
      cause.

PMID- 16950582
TI  - Anti-inflammatory activity of hexane leaf extract of Aspilia africana C.D. Adams.
AB  - The anti-inflammatory activity of hexane leaf extract of Aspilia africana C.D.
      Adams (Compositae) was evaluated in rodents using the xylene-induced ear edema,
      egg albumin- and agar-induced paw edema, formaldehyde-induced arthritis, cotton
      pellet granuloma, gastric ulcerogenic, acetic acid-induced vascular permeability
      and dextran-induced in vivo leukocyte migration tests. Results showed that the
      extract (5mg/ear) inhibited topical edema in the mouse ear and at 200 and
      400mg/kg (i.p.), it significantly (P<0.05) suppressed the development of egg
      albumin- and agar-induced paw edema, and the global edematous response to
      arthritis induced by formaldehyde in rats. Oral administration of the extract
      (200 or 400mg/kg) evoked a significant (P<0.05) dose-related ulceration of the
      rat gastric mucosa and inhibition of vascular permeability induced by acetic acid
      in mice. The extract also significantly (P<0.05) reduced total leukocyte and
      neutrophils counts in a non-dose-related manner. However, it significantly
      (P<0.05) increased lymphocyte counts and stimulated the growth of granuloma
      tissues induced by subcutaneously implanted cotton pellets in rats. Phytochemical
      tests showed that the extract contained sterols and terpenoids. These findings
      suggest that the leaves of Aspilia africana possess anti-inflammatory activity in
      acute and certain aspects of chronic inflammation, which may derive from
      inhibition of prostaglandins synthesis, inhibition of increased vascular
      permeability, inhibition of neutrophil migration into inflamed tissues, and
      stimulation of lymphocyte accumulation, which may enhance tissue repair and
      healing. The terpenoids present in the leaves may account for the anti
      inflammatory activity.

PMID- 16950583
TI  - Taraxacum--a review on its phytochemical and pharmacological profile.
AB  - The genus Taraxacum is a member of the family Asteraceae, subfamily
      Cichorioideae, tribe Lactuceae and widely distributed in the warmer temperate
      zones of the Northern Hemisphere. The perennial weed has been known since ancient
      times for its curative properties and has been utilized for the treatment of
      various ailments such as dyspepsia, heartburn, spleen and liver complaints,
      hepatitis and anorexia. However, its use has mainly been based on empirical
      findings. This contribution provides a comprehensive review of the
      pharmacologically relevant compounds of Taraxacum characterized so far and of the
      studies supporting its use as a medicinal plant. Particular attention has been
      given to diuretic, choleretic, anti-inflammatory, anti-oxidative, anti
      carcinogenic, analgesic, anti-hyperglycemic, anti-coagulatory and prebiotic
      effects. Finally, research needs such as quantification of individual Taraxacum
      constituents and assessment of their pharmacological activities in humans have
      briefly been outlined.

PMID- 16950584
TI  - Screening of selected Indian medicinal plants for acetylcholinesterase inhibitory
      activity.
AB  - Seventy-six plant extracts including methanolic and successive water extracts
      from 37 Indian medicinal plants were investigated for acetylcholinesterase (AChE)
      inhibitory activity (in vitro). Results indicated that methanolic extracts to be
      more active than water extracts. The potent AChE inhibiting methanolic plant
      extracts included Withania somnifera (root), Semecarpus anacardium (stem bark),
      Embelia ribes (Root), Tinospora cordifolia (stem), Ficus religiosa (stem bark)
      and Nardostachys jatamansi (rhizome). The IC(50) values obtained for these
      extracts were 33.38, 16.74, 23.04, 38.36, 73.69 and 47.21mug/ml, respectively.
      These results partly substantiate the traditional use of these herbs for
      improvement of cognition.

PMID- 16950585
TI  - Searching for the origin of Romanies: Slovakian Romani, Jats of Haryana and Jat
      Sikhs Y-STR data in comparison with different Romani populations.
AB  - Haplotype frequencies for 11 Y-STR markers (DYS19, DYS389I, DYS389II, DYS390,
      DYS391, DYS392, DYS393, DYS385, DYS437, DYS438 and DYS439) in a Romani population
      (n=63) from Slovakia, Jats of Haryana (n=84) and Jat Sikhs (n=80) from India were
      determined. The Slovakian Romani, the Haryana and Sikh populations were
      endogamous based on their unique haplotype ratio and haplotype diversity values,
      although the Sikh population appeared to be more diverse. AMOVA revealed non
      significant differences between the Romanies and significant differences with non
      Romani populations. The Macedonian Romani population differed from all Romani
      populations examined. Frequent haplotypes observed in Romani populations were
      sporadic in northwest Indian populations. Thirteen out of 316 populations
      worldwide were found to share the six most frequent haplotypes of the Slovakian
      Romanies when the screening conditions were narrowed based on the population size
      to be over 40, the occurrence of the haplotypes was more than one and the sum
      frequencies of the most frequent haplotypes was at least 0.02. The most common
      haplotypes were also observed in other Romani groups. When searching with two
      Indian (Malbar and Malaysian Indian) most frequent haplotypes under the same
      conditions matches could be detected in all Romani populations except for the
      Macedonian Romanies. The search with the Jat Sikhs and Jats of Haryana most
      frequent haplotypes resulted no matches in Romani populations.

PMID- 16950586
TI  - Structural identification and characterization of impurities in ceftizoxime
      sodium.
AB  - Ceftizoxime sodium is a parenteral beta-lactamic antibacterial drug. In the
      synthesis of ceftizoxime sodium, eight process related impurities were detected
      in HPLC analysis. Pure impurities obtained by both synthesis and preparative HPLC
      were co-injected with ceftizoxime sample to confirm the retention times in HPLC.
      The impurities were characterized as, (6R,7R)-7-amino-3-cephem-4-carboxylic acid
      (impurity I); (6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-(methoxyimino)acetamido]-3
      cephem-1-oxo-4-carboxylic acid (impurity II); (4RS,6R,7R)-7-[(Z)-2-(2-amino-4
      thiazolyl)-2-(methoxyimino) acetamido]-3,4-dihydro-3-cephem-4-carboxylic acid
      (impurity III); (6R,7R)-7-[(E)-2-(2-amino-4-thiazolyl)-2-(methoxyimino)acetamido]
      3-cephem-4-carboxylic acid (impurity IV); (6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)
      2-(methoxyimino)acetamido]-3-cephem-N-(3-cephem-4-carboxy-7-yl)-4-carboxamide
      (impurity V); (6R,7R)-7-[(Z)-2-[[(Z)-2-(2-amino-4-thiazolyl)-2
      (methoxyimino)acetylamino]thiazol-4-yl]-2-methoxyiminoacetamido]-3-cephem-4
      carboxylic acid (impurity VI); 2-mercaptobenzothiazole (impurity VII) and 2
      mercapto benzothiazolyl [(Z)-2-(2-amino-4-thiazolyl)-2-methoxyimino] acetate
      (impurity VIII). Structural elucidation of all impurities by spectral data ((1)H
      NMR, (13)C NMR, MS and IR) has been discussed.

PMID- 16950587
TI  - Voltammetry and quantification of the contraceptive drug norethisterone in bulk
      form and pharmaceutical formulation.
AB  - The electrochemical behavior of norethisterone at the mercury electrode was
      studied in the universal buffer of various pH values using dc-polarography,
      cyclic voltammetry and controlled-potential electrolysis. Norethisterone was
      reduced at the mercury electrode via the consumption of two electrons
      corresponding to reduction of the 3-keto-delta-4-group in the A-ring of the
      molecule. The pK(a) value (8.7) of norethisterone was determined from the
      polarographic and spectrophotometric measurements. A fully validated, simple,
      sensitive, precise and inexpensive square-wave adsorptive cathodic stripping
      (SWAdCS) voltammetry procedure was described for trace quantification of bulk
      norethisterone. The stripping voltammetry peak current of norethisterone in a
      universal buffer of pH 5 following its accumulation onto the hanging mercury drop
      electrode (HMDE) at -0.6 V (versus Ag/AgCl/KCl(s)) for 130 s showed a linear
      response with the concentration over the range 5 x 10(-9) to 3 x 10(-7)M
      norethisterone. Detection and quantitation limits of 1.5 x 10(-9) and 5 x 10(-9)M
      bulk norethisterone, respectively, were achieved. The proposed procedure was
      successfully applied for the assay of norethisterone in Steronate tablets without
      interference from excipients.

PMID- 16950588
TI  - Hydrolytic kinetics of lithospermic acid B extracted from roots of Salvia
      miltiorrhiza.
AB  - The hydrolytic kinetics of lithospermic acid B (LAB) extracted from the roots of
      Salvia miltiorrhiza (Chinese herb: danshen) was investigated by using reversed
      phase high-performance liquid chromatography (HPLC) with UV-vis detection. The
      influences of initial drug concentration, pH and temperature on hydrolysis of LAB
      were studied in aqueous solutions. The results showed that initial concentration
      of LAB has no effect on the degradation rate at pH 2.0. The hydrolysis followed
      pseudo-first-order kinetics at 90 degrees C. The log k(obs)-pH profile indicated
      that the optimal stability range was at pH 2.0-5.0. The rate constant of overall
      hydrolysis as a function of temperature under the given conditions obeyed the
      Arrhenius equation. Analysis of the acid-induced degraded solution of LAB by
      liquid chromatography-mass spectrometry (LC-MS) revealed at least four
      degradation products [M-H](-) ion at m/z 197, 137, 537 and 537, respectively.
      Three of these degradation products, i.e. danshensu (DSU), protocatechuic
      aldehyde (PRO), and lithospermic acid, were further identified by comparing the
      retention times with standard samples. According to the structure of LAB and its
      hydrolysis behavior in solution, the other product was proposed to be the isomer
      of lithospermic acid.

PMID- 16950589
TI  - High performance liquid chromatographic determination of a new antifungal
      compound, ADKZ in rat plasma.
AB  - A high performance liquid chromatography (HPLC) method was developed and
      validated for the determination of ADKZ (1-(1H-1,2,4-triazole)-2-(2,4
      diflurophenyl) -3-[N-methyl-N-(4-iodo-benzyl)amino]-2-propanol) in rat plasma.
      The compound was extracted from plasma samples by liquid-liquid extraction, and
      an isomeric compound of ADKZ (1-(1H-1,2,4-triazole)-2-(2,4-diflurophenyl)-3-[N
      methyl-N -(3-iodo-benzyl)amino]-2-propanol) was used as the internal standard
      (IS), which were analyzed on a reversed-phase C18 column (5 microm, 200 mm x 4.6
      mm i.d.). The extracted plasma samples were eluted with acetonitrile-0.018 M
      triethylamine solution adjusted to pH 3.2 with phosphoric acid (35:65, v/v). The
      effluent was monitored by a UV detector at 230 nm. The retention time of ADKZ was
      7.1 min and IS 8.2 min. The calibration curves were linear in the concentration
      range of 0.02-2.00 microg/ml with the correlation coefficients greater than
      0.999. The quantification limit of ADKZ in rat plasma was 0.02 microg/ml. Intra-
      and inter-day precision ranged from 2.6 to 7.9% and 3.1 to 9.6%, respectively.
      The extraction recovery from plasma was no less than 80%. No endogenous
      interferences were observed with either ADKZ or IS. The method has been
      successfully used to support the pre-clinical pharmacokinetic studies of ADKZ in
      rats.

PMID- 16950590
TI  - Method development for dihydralazine with HPLC-MS/MS--an old but tricky substance
      in human plasma.
AB  - An HPLC-MS/MS method was developed and validated for the determination of
      dihydralazine in human plasma. HPLC-MS/MS has not been used before in a published
      paper and provides better sensitivity and selectivity. Therefore a much easier
      sample preparation than published before is feasible (protein precipitation). As
      this substance is rather reactive and sensitive some specific care has to be
      taken hindering the conversion of the substance in whole blood and following
      human plasma after blood withdrawal. Hydrazines often are used for derivatization
      of aldehydes and ketones. With specific care (using 1,4-dithiothreitol (DTT) and
      cooling) dihydralazine can be preserved and analysed without decomposition or
      conversion in the tested range of 0.500-302 ng/mL of human plasma. The following
      inter-batch precision and accuracy of the Quality Control Samples resulted: QC-A
      (1.34 ng/mL plasma) with a precision of coefficient of variation (CV) 7.66% and
      an accuracy of 103.2%; QC-B (18.2 ng/mL 7.86%, acc. 101.3%); QC-C (258 ng/mL,
      9.73%, acc. 98.3%). The inter-batch values of the LLOQ samples at 0.500 ng/mL
      were 7.17% for CV and accuracy of 106.4%. Mean recovery tested at the QC levels
      was found to be 103.8%. Specificity in six different plasma samples was good
      (<10% of the area of the LLOQ). Stability in plasma was tested under different
      conditions and was sufficient.

PMID- 16950591
TI  - Social problem solving training for African Americans: effects on dietary problem
      solving skill and DASH diet-related behavior change.
AB  - OBJECTIVE: Hypertension continues to take its toll on millions of African
      Americans. Adhering to an eating plan called Dietary Approaches to Stop
      Hypertension (DASH) can significantly lower blood pressure. This study examined
      whether problem solving training in addition to education on DASH is more
      effective than education alone to help African Americans in an urban community
      college setting solve their own dietary problems and change eating behaviors that
      could affect blood pressure. METHODS: A randomized, two groups, multiple post
      test design was used. All participants (N=78, 59% female) completed a Problem
      Solving Instrument immediately post-intervention and a follow-up Telephone
      Interview 2 weeks later. RESULTS: Fewer than half had normal blood pressure on
      screening. The Experimental Group identified and implemented significantly higher
      quality solutions to the second of their two problems than the Control Group. The
      intervention effect was the greatest for participants with blood pressure
      screenings above normal. CONCLUSION: Problem solving training combined with
      nutrition information may help African Americans to deal more effectively with
      dietary problems especially when the problems are complex or less well-defined.
      PRACTICE IMPLICATIONS: Dietary interventions that include a focus on everyday
      problem solving as well as knowledge acquisition can be developed in clinical,
      community health, school, and worksite settings.

PMID- 16950592
TI  - A modified radiofrequency-assisted approach to right hemihepatectomy.
AB  - AIMS: To evaluate a modified radiofrequency-assisted approach to right
      hemihepatectomy. METHODS: Following a bilateral subcostal incision and
      intraoperative ultrasonography, the liver was mobilized in the standard manner,
      and a cholecystectomy was performed. The portal vein was isolated, encircled, and
      ligated. After demarcating the liver parenchyma, coagulation necrosis was
      achieved using a radiofrequency-assisted device along the line demarcated for
      transecting the liver parenchyma. The actual transection of the liver parenchyma
      and the right portal vein was done using a surgical scalpel along the
      radiofrequency-coagulated line. The right hepatic vein was coagulated using the
      radiofrequency sealer or by stitching in the resection plane. The hepatic artery
      was not dissected and was sealed together with the bile ducts in the resection
      plane using the radiofrequency instrument. The hepatic vein was not divided.
      RESULTS: Between July 2005 and July 2006, a total of 49 liver resections were
      performed in our unit. Of these, the radiofrequency-assisted technique was used
      in 33 cases with metastatic disease; 14 of these cases had right
      hemihepatectomies, including 2 repeat resections. The mean operation time was
      180min (range, 120-240min), and the average blood transfusion was 0.14U (range, 0
      2U). Postoperatively, there was no morbidity, such as bleeding, infection, or
      biliary fistula, related to the liver resection technique, and no patients died
      as a result of surgery. In 8 out of the 14 right hemihepatectomies, a right-sided
      pleural effusion was observed; 3 of them required evacuation. CONCLUSION: This
      paper describes a modified radiofrequency-assisted hemihepatectomy, which allows
      one to obtain control of the portal blood flow going into the resected part of
      liver. The modified approach appears to be simple and safe.

PMID- 16950593
TI  - Metastatic breast cancer: an updating.
AB  - This article reports on recent advances on metastatic breast cancer. Detection,
      prognostic factors, predictors of response to therapy and therapy, with
      particular regard to targeted therapies, were examined. DETECTION: Unlike current
      guidelines that yet do not routinely recommend intensive clinical-instrumental
      post-operative follow-up of breast cancer patients, relatively large data
      collected in the last decades have shown that an intensive post-operative follow
      up with 'dynamic evaluation' of a suitable tumour marker panel precedes a few
      months as average the clinical and/or instrumental sign of a pending relapse in
      most relapsed patients and largely limits the use of the common instrumental
      examinations. PROGNOSIS AND THERAPY PREDICTORS: Disease-free interval (DFI)<or=24
      months, adjuvant chemotherapy, liver and distant soft tissue involvement or
      DFI>24 months and disease confined to bony skeleton are prognostic factors more
      often correlated with relatively poor or prolonged survival, respectively.
      Estrogen receptor (ER) expression in primary tumour and at the relapse correlates
      strongly with response to salvage hormone therapy and data from large trials
      showed that 38-59% of ER and/or PR+ post-menopausal patients had clinical benefit
      from first line tamoxifen or aromatase inhibitors. An inverse correlation of ER
      with epidermal growth factor receptor (EGFR) has been found. The co-expression of
      HER-2/neu and/or elevated serum HER-2/neu protein level were associated with a
      low rate and shorter duration of response of ER+ patients to first line hormone
      therapy. Accordingly, ER-EGFR- compared with ER-EGFR+ tumours are usually more
      responsive to endocrine therapy. High class III beta-tubulin expression or fall
      in insulin-like growth factor binding protein-3 (IGFBP-3) from baseline levels
      have been found to significantly predict resistance to chemotherapeutic agents.
      THERAPY: Liposomes as carrier of doxorubicin (Caelix, Evacet, Myocet) is one
      approach to decrease the anthracycline-related cardiac toxicity. Weekly
      paclitaxel or docetaxel and oral formulation of vinorelbine and 5-fluorouracil (5
      FU) (capecitabine) provide new effective and well tolerated options that reach
      greater dose intensity and cumulative dose than with the conventional schedules.
      As to the so called 'tailored' or targeted therapies, the more potent and highly
      selective third generation of aromatase inhibitors (letrozole, anastrozole,
      exemestane) targeting ER+ tumours by estrogen deprivation, challenge tamoxifen as
      current standard first line therapy in postmenopausals. One pilot study showed
      that stimulation of cellular immunity by the addition of beta-interferon
      interleukin-2 sequence in patients on clinical benefit on first line tamoxifen
      significantly prolonged median overall survival (OS) and duration of response
      compared to that observed in similar patients only treated with tamoxifen.
      Trastuzumab, a humanised monoclonal antibody to extracellular domain of HER-2,
      plus conventional chemotherapy has become a standard of care for women with
      overexpressing HER-2 tumours. Bevacizumab is a recombinant humanised monoclonal
      antibody to vascular endothelial growth factor (VEGF) that in refractory
      metastatic breast cancer doubled the response rate of capecitabine although it
      did not affect survival. Finally, the so called 'oligometastatic' and a few stage
      IV diseases are conditions amenable to be rendered with no evidence of disease
      (NED) after local surgery and/or radiation. In both, as well as in complete
      responders to chemotherapy, minimal residual disease (m.r.d.) likely continues to
      be present. Recent data suggest that 'biological' therapy (immunomodulators
      and/or retinoids with or without hormone therapy), might be suitable to be
      successfully tested in these patients as maintenance treatment given soon after
      local intervention or chemotherapy.

PMID- 16950594
TI  - Detection of bovine herpesvirus 4 in aborted bovine placentas.
AB  - Diagnostic studies on aborted placentas of cattle usually do not determine any
      reason for abortions. In this paper, five bovine herpesviruses (BoHVs) and some
      bacteriological agents were investigated by several methods in 33 aborted bovine
      placentas. Inclusion bodies, PCR and in situ DNA hybridization proved the
      presence of BoHV-4 DNA in six (18.18%) tested placentas. Positive DNA
      hybridization signal localized BoHV-4 DNA to placental epithelial cells
      macrophages and lymphocytes. By destroying epithelial cells and provoking local
      immune response BoHV-4 infection may inhibit physiological functions of the
      placenta during gestation. This finding is a further sign that BoHV-4 plays an
      active role in reproductive disorders of cattle.

PMID- 16950595
TI  - Proteomic analyses of murine macrophages treated with Bacillus anthracis lethal
      toxin.
AB  - Bacillus anthracis is the etiological agent of anthrax and the bacterium produces
      a tripartite anthrax toxin composed of protective antigen (PA), lethal factor
      (LF) and edema factor (EF). PA represents the binding domain of the toxin and
      acts in concert with either LF, a metalloprotease, or EF, an adenylate cyclase,
      to form lethal toxin (LeTx) or edema toxin (EdTx), respectively. We analyzed the
      proteomics response of two murine macrophage cell lines (J774.1A and RAW264.7)
      following B. anthracis LeTx treatment to detect unique host proteins involved in
      anthrax infection using difference in-gel electrophoresis (DIGE) followed by
      nanoLC-MS for identification of the proteins. The comparative proteomics approach
      identified a set of proteins in each cell line that was consistently upregulated
      when the two macrophage cell lines were treated with LeTx. The upregulated
      proteins include those involved in energy metabolism, cytoskeleton structure and
      stress response. A subset of five proteins (ATP synthase beta subunit, beta
      actin, Hsp70, vimentin, and Hsp60 homolog) was identified that were commonly
      upregulated in both cell lines. The proteomic data suggest the involvement of
      reactive oxygen species (ROS) in cell lysis as seen by the upregulation of
      proteins that lead to the production of ROS in both the cell lines used in our
      study. However, proteins that afford protection against ROS may play an important
      role in the survival of the macrophage to LeTx infection as shown by the
      differences in proteomic responses of the two cell lines to the action of LeTx.
      These identified proteins may have the potential to be used as biomarkers for
      diagnostics and therapeutics.

PMID- 16950596
TI  - Effects of steatosis on drug-metabolizing capability of primary human
      hepatocytes.
AB  - The suitability of liver grafts discarded for transplantation because of
      macrosteatosis for preparing human hepatocyte cultures for in vitro drug
      metabolism studies has been examined. Lower cell viability and yield of isolation
      procedure were obtained from fatty livers (>40% steatosis) with respect to normal
      tissue. Significant reductions in 7-ethoxycoumarin O-deethylation (ECOD) and
      testosterone oxidations were found in hepatocytes prepared from steatotic livers.
      The potential impact of lipid accumulation on P450 enzymes was studied in vitro
      by incubation of cultured hepatocytes with long chain free fatty acids (FFA).
      Treatment of cells with 0.25-3mM FFA induced dose-dependent accumulation of
      lipids in the cytosol. Decreased ECOD and testosterone oxidation were found after
      14h of exposure to 1mM or 2mM FFA (about 60-70% and 30-60% of control,
      respectively). The effects of fat-overloading on individual P450s were analyzed
      both at activity and mRNA level. CYP1A2, CYP2C9, CYP2E1 and CYP3A4 activities
      were reduced after hepatocyte incubation with 1mM (to 45-65% of control) or 2mM
      (to 20-50%) FFA for 14h. Reductions in P450 transcripts were also found in
      hepatocytes treated with 1mM FFA. Our findings showed a general down-regulation
      of P450s involved in drug metabolism in fat-overloaded hepatocytes. The results
      suggest that, despite their reduced P450 function, human hepatocytes obtained
      from donors with steatosis are metabolically competent and could be used for drug
      metabolism studies.

PMID- 16950597
TI  - Detection of the single nucleotide polymorphism causing feline autosomal-dominant
      polycystic kidney disease in Persians from the UK using a novel real-time PCR
      assay.
AB  - Autosomal-dominant polycystic kidney disease (AD-PKD) is the most prevalent
      inherited genetic disease of cats, particularly affecting Persians. Until
      recently the condition has been diagnosed by renal ultrasound screening. With the
      identification of the genetic mutation responsible for AD-PKD it is now possible
      to use advanced molecular techniques to screen for the disease. We have developed
      a rapid, sensitive and specific real-time PCR genotyping assay that can detect
      the single nucleotide polymorphism responsible for AD-PKD. Of 72 UK Persian and
      Exotic Shorthair cats submitted for AD-PKD ultrasound screening, 29 were found to
      have the disease, 41 were negative and 2 were equivocal. The recently published
      PCR-RFLP method showed the AD-PKD mutation to be present in all 29 diseased cats
      and absent in the 41 negative and 2 equivocal cats. Our real-time PCR genotyping
      assay was in complete agreement with the PCR-RFLP results. Of 600 blood or buccal
      swabs analysed from April 2005 to January 2006, 165 were found to be AD-PKD
      positive and 435 were negative, giving a prevalence of 27.5%. All 194 cats with
      AD-PKD were found to be heterozygous for the mutation.

PMID- 16950599
TI  - Voice problems of future speech-language pathologists.
AB  - Students training to be educators frequently exhibit voice disorders prior to
      employment. To date, there exist no similar studies of future speech-language
      pathologists (SLPs). The study is designed as a prospective, nonrandomized
      survey. The objective of this study is to determine the voice problems of first
      year graduate students training to be SLPs. Participants were 104 first year
      graduate students majoring in speech-language pathology at two universities. The
      Quick Screen for Voice was administered. Participants who failed completed a
      questionnaire regarding voice problems, medical history, daily habits, and voice
      use. When responses further indicated voice-related problems, endoscopic
      examination was completed. Fourteen percent (N=15) of the participants failed the
      screening by demonstrating two or more abnormal voice characteristics. These
      included persistent glottal fry (present in all who failed), low habitual pitch,
      juvenile resonance, hoarse, breathy, or strained phonation, abnormally low pitch
      on sustained vowels, and voice breaks during the frequency range. Twelve percent
      (N=12) failed both the screening and follow-up questionnaire. Responses included
      self-reported dysphonia, medical history with voice-related side effects,
      difficulty with excessive voice use, and voice problems occurring daily or
      weekly. Endoscopic evaluation showed one participant with bilateral vocal
      nodules. The results suggest that voice problems among future SLPs (12%) are more
      common than the 3-9% reported in the general population and similar to the 11%
      previously reported for teachers. However, future SLP voice problems are less
      frequent than those reported among education majors (21%) and all college
      students (17%). Faculty should identify students with voice problems and
      emphasize optimal voice use in classroom and clinical settings.

PMID- 16950598
TI  - Cognitive-behavioral treatment for specific phobias with a child demonstrating
      severe problem behavior and developmental delays.
AB  - Cognitive-behavioral treatments (CBTs) are widely used for anxiety disorders in
      typically developing children; however, there has been no previous attempt to
      administer CBT for specific phobia (in this case study, one-session treatment) to
      developmentally or intellectually disabled children. This case study integrates
      both cognitive-behavioral and behavior analytic assessment techniques in the CBT
      of water and height phobia in a 7-year-old male with developmental delays and
      severe behavior problems. One-session treatment [Ost, L. G. (1989). One-session
      treatment for specific phobias. Behaviour Research and Therapy, 27, 1-7; Ost, L.
      G. (1997). Rapid treatment of specific phobias. In G. C. L. Davey (Ed.), Phobias:
      A handbook of theory, research, and treatment (pp. 227-247). New York: Wiley] was
      provided for water phobia and then 2 months later for height phobia. The massed
      exposure therapy sessions combined graduated in vivo exposure, participant
      modeling, cognitive challenges, reinforcement, and other techniques. Both
      indirect and direct observation measures were utilized to evaluate treatment
      efficacy. Results suggested CBT reduced or eliminated behavioral avoidance,
      specific phobia symptoms, and subjective fear. Negative vocalizations were
      reduced during height exposure following treatment. Vocalizations following
      treatment for water phobia were less clear and may have been indicative of
      typical 7-year-old protests during bath time. Findings indicate CBT can be
      effective for treating clinical fears in an individual with developmental
      disabilities and severe behavior. Future research in this population should
      examine CBT as an alternative to other techniques (e.g., forced exposure) for
      treating fears.

PMID- 16950600
TI  - Fundamental frequency change during offset and onset of voicing in individuals
      with Parkinson disease.
AB  - SUMMARY: After years of treatment with the medication levodopa, most individuals
      with Parkinson disease (PD) experience fluctuations in response to their
      medications. Although relatively consistent perceptual voice improvements have
      been documented to correspond with these fluctuations, consistent quantitative
      data to support this finding are lacking. This mismatch may have occurred because
      most of this phonation research has centered on long-term phonatory measures (ie,
      across speaking samples and prolonged vowel tasks). The current study examined
      short-term phonatory behavior in individuals with PD, specifically examining
      fundamental frequency (F0) at the offset and onset of phonation, before and after
      a voiceless consonant. The F0 analysis at phonatory offset supported the
      conclusion that individuals with PD have difficulty with the rapid offset of
      voicing, and that they are stopping vocal fold vibration primarily through vocal
      fold abduction (without adding tension). The F0 analysis at phonatory onset
      revealed that all groups use some laryngeal tension at the initiation of voicing.
      The tension was lowest for the PD participants who were in their OFF medication
      state, and it was highest for the age-matched control participants and the PD
      participants in their ON medication states.

PMID- 16950601
TI  - Patient versus partner perception of voice handicap.
AB  - The primary purpose of this study was to compare patient's and communication
      partner's perceptions of handicap secondary to dysphonia. A secondary purpose was
      to compare patient health-related quality of life (HRQOL) to that of speakers
      with normal voice. Participants were 20 adults (mean age=69.15 years) with
      dysphonia and their communication partners. Patients completed the Voice Handicap
      Index (VHI), a questionnaire of self-perceived voice handicap, and the Short-Form
      36 (SF-36), a general health questionnaire. Partners completed the Voice Handicap
      Index-Partner (VHI-P), a questionnaire derived from the VHI for this pilot study,
      to gauge partner perception of voice handicap. Patients in this study viewed
      themselves as only moderately handicapped by their dysphonia and their partners
      were in close agreement. Patients and their partners were also in close agreement
      on each of three VHI subscales (physical, functional, and emotional), and in all
      cases the physical domain was perceived by both patients and their partners to be
      most handicapped. Patients had lower SF-36 mean scores than those of persons with
      normal voice from the general U.S. population on scales assessing physical
      functioning, physical role, general health, vitality, social functioning,
      emotional role, and mental health. The results of this study are consistent with
      previous studies examining patient-partner agreement, which consider proxy
      ratings to be a useful alternative or collaborative source of patient's self
      perception. Further research regarding the reliability of patient and partner
      agreement is necessary to most effectively assess and manage patients with
      dysphonia.

PMID- 16950602
TI  - Epigallocatechin gallate (EGCG) mimics insulin action on the transcription factor
      FOXO1a and elicits cellular responses in the presence and absence of insulin.
AB  - The green tea flavonoid epigallocatechin gallate (EGCG) is one of several
      compounds that have been reported to have insulin-like glucose-lowering
      properties in mammals. EGCG is understood to act at least in part by repression
      of gluconeogenic genes such as phosphoenolpyruvate carboxykinase but the
      transcription factors that are targeted to achieve this are unknown. We show here
      that EGCG induces phosphorylation of insulin-sensitive residues on the
      transcription factor FOXO1a. Like insulin, EGCG induced FOXO1a phosphorylation is
      abolished by the PtdIns 3-kinase inhibitor LY294002 but not by PD98059 (an
      inhibitor of mitogen-activated protein kinase cascade) or by rapamycin (an
      inhibitor of signalling to p70 S6 kinase). EGCG differs from insulin and IGF-1
      however, in that its induction of FOXO1a phosphorylation is sensitive to
      scavengers of reactive oxygen species (ROS). These results indicate that EGCG
      exerts its insulin mimetic effects at least in part by phosphorylation of the
      FOXOs through a mechanism that is similar but not identical to insulin and IGF-1
      induced FOXO phosphorylation. Our results suggest that agents acting in the
      manner of EGCG may be useful antidiabetic agents.

PMID- 16950603
TI  - Attentional network task performance in patients with schizophrenia-spectrum
      disorders: evidence of a specific deficit.
AB  - Although attentional deficits are frequently displayed by schizophrenia and
      spectrum patients, the precise nature of the impairment is unclear. The present
      study investigates attentional performance in 26 schizophrenia-spectrum
      outpatients and 24 healthy controls using the Attentional Network Task (ANT). We
      assessed the efficiency of the segregated alerting, orienting, and executive
      control networks by measuring how response latencies were influenced by alerting
      cues, spatial cues, and flanking stimuli. In overall ANOVAs we found main effects
      of cue condition and flanker congruency. The data also revealed a significant
      interaction of group and flanker type, with schizophrenia-spectrum patients
      taking longer on average to resolve conflict. These results suggest that compared
      to the healthy nonpatients, schizophrenia-spectrum patients show a deficit in
      their executive control network. Considered together, these findings support the
      notion that schizophrenia-spectrum patients have a specific attentional deficit,
      rather than a global one. The significance of these findings is considered from
      both experimental and clinical perspectives.

PMID- 16950604
TI  - Neurokinin 1 receptor antagonism requires norepinephrine to increase serotonin
      function.
AB  - The present studies examined the role of norepinephrine (NE) system in mediating
      the enhancement of 5-HT function produced by neurokinin (NK)1 receptor
      antagonism. Dorsal raphe 5-HT and locus coeruleus NE neurons were recorded in
      vivo in mice lacking NK1 receptors in wildtype mice pretreated with the NK1
      antagonist RP67580 and its inactive enantiomer RP 68651. RP67580 and RP68651 were
      also tested on 5-HT neurons of mice lacking the 5-HT(1A) receptor. RP67580
      increased the firing rate of 5-HT neurons in wildtype mice and in 5-HT(1A) null
      mutant mice to the same degree, thus indicating that the mechanism by which NK1
      antagonists enhances 5-HT firing is independent of 5-HT(1A) receptors. NE
      neuronal burst activity was increased in NK1 null mutant and wildtype mice given
      RP67580, but not with RP68651. After NE depletion, RP67580 was ineffective in
      increasing 5-HT neuronal firing activity in NK1 wildtype mice, and the
      enhancement of 5-HT neuronal firing observed in NK1 null mutant mice was
      abolished. In conclusion, NE neurons are essential for the action of NK1
      antagonists on 5-HT neurons. In addition, the desensitization of 5-HT(1A)
      autoreceptors produced by NK1 receptor antagonism is not critical for enhancing 5
      HT neuronal firing.

PMID- 16950605
TI  - The strength of bilayered tablets.
AB  - The tensile strength of model materials (dicalcium phosphate dihydrate,
      microcrystalline cellulose and pregelatinised starch) compacted to form tablets
      in the form of beams consisting of two layers of equal thickness has been
      determined by three-point loading. The values of the tensile strength of the
      materials were sometimes higher and sometimes lower than the tensile strength of
      beams of the same thickness composed of a single material. Correction of the
      values for the tensile strength of the layered beams for the differences in the
      elasticity of the materials in the layered tablets failed to correct for these
      differences, as did considering the layered beams as beams of half thickness. For
      a layered tablet with pregelatinised starch at the bottom and microcrystalline
      cellulose at the top, the value of the tensile strength recorded appeared to be
      that of the microcrystalline cellulose as the fracture propagated across the
      boundary between the layers and into microcrystalline cellulose. What appeared to
      be the important factor was the way the failure of the beam crossed the interface
      between the two layers.

PMID- 16950606
TI  - Regulatory aspects of drug dissolution from a European perspective.
AB  - The need for an early identification of formulation and manufacturing factors
      that are important for setting satisfactory specification limits for the
      dissolution rate of an active substance from a dosage form is emphasized. A
      discriminatory dissolution test has to be developed based on experiences from
      early drug development, bioavailability/bioequivalence studies and clinical
      trials. References are given to guidelines of the EU-system and to the monographs
      and chapters of the European Pharmacopoeia, which have to be considered. The
      dissolution test is expected to be an appropriate tool for checking that the
      manufacture of dosage forms is consistent and successful and that each dosage
      unit of a batch will have pharmaceutical qualities that correspond to those on
      which the safety and efficacy documentation of a product is based.

PMID- 16950607
TI  - Release characteristics of salmon calcitonin from dextran hydrogels for colon
      specific delivery.
AB  - Biodegradable dextran hydrogels were synthesized by crosslinking dextran (T-70)
      with epichlorohydrin (ECH) for the in vitro colon-specific delivery of salmon
      calcitonin (sCT). Crosslinking reaction was performed in 2.8 M NaOH solution both
      in the presence and absence of ethanol at 10 and 23 degrees C. Biodegradation
      kinetics of dextran hydrogels were studied and, in the presence of 0.7 IU ml-1
      dextranase, dextran discs lost 71.0% and 56.5% of their dry weight within 80 h at
      pH 5.5 and 7.0, respectively. sCT was derivatized with the fluorescamine (FSM) at
      borate buffer (pH 9.0) and the quantitative determinations were performed using
      spectrofluorimetric method (lambdaex: 390 nm, lambdaem: 475 nm). In vitro release
      studies for the hydrogels prepared in the presence of ethanol were carried out in
      simulated gastrointestinal fluids. Results indicated that 84.9% of the loaded-sCT
      was released for 17 h and dextran hydrogel prepared in the presence of ethanol
      may be a good delivery device for the colon-specific delivery of other peptide
      type drugs as well as sCT.

PMID- 16950608
TI  - Trehalose and hyaluronic acid coordinately stabilized freeze-dried pancreatic
      kininogenase.
AB  - The ability and mechanisms of stabilization of freeze-dried formulations of
      pancreatic kininogenase (PKase) by carbohydrates were evaluated. Activity and
      structure of PKase were examined after freeze-drying and rehydration in presence
      with or without a carbohydrate. Addition of trehalose, lactose, sucrose,
      hyaluronic acid (HA) or a combination of trehalose and HA to PKase formulations
      prior to freeze-drying step increases the stability of PKase during freeze
      drying, storage and rehydration as measured by activity preservation. The
      combination of trehalose and HA is the most effective for the stabilization of
      PKase. Addition of HA alone to a formulation does not affect protein structure,
      but it increases glass-transition temperature (Tg) and stability of lyophilized
      PKase in presence of trehalose during dehydration, storage and rehydration
      processes. Therefore, trehalose and HA offer complementary properties that
      improve the stability of PKase during dehydration, storage and rehydration.

PMID- 16950609
TI  - Development and characterization of film forming polymeric solutions for skin
      drug delivery.
AB  - Film forming polymeric solutions as a novel approach for skin drug delivery were
      developed and characterized concerning their mechanical properties and water
      vapor permeability. They were developed by varying type and content of the film
      forming polymer as well as nature and content of the plasticizer. The resulting
      formulations were evaluated according to five criteria: drying time, cosmetic
      attractiveness, outward stickiness, integrity on skin (after 18 h) and viscosity.
      Among the 14 tested polymers 10 film formers yielded formulations with a positive
      evaluation in all five test criteria. Selected formulations were then
      investigated for tensile strength and elongation at break in vitro and for water
      vapor permeability in vitro (WVP) and in vivo (TEWL). Their mechanical properties
      determined in vitro were found to be not predictive for the flexibility and
      abrasion resistance observed on living skin. Similar to this, the results derived
      from the WVP and the TEWL methods were not in accordance with each other.
      Obviously, the investigated in vitro methods do not characterize the properties
      of the thin films on living skin satisfactorily. Nevertheless, the identified
      film forming solutions are a promising approach and will provide the basis for
      the further development of this novel dosage form.

PMID- 16950610
TI  - Dual electrochemical determination of glucose and insulin using enzyme and
      ferrocene microcapsules.
AB  - Dual electrochemical determination of glucose and insulin has been developed,
      based on enzymatic reaction and immunoassay with utilization of ferrocene
      microcapsules, respectively. Glucose was determined through electrochemical
      oxidation of formed product, hydrogen peroxide, by the action of glucose oxidase
      (GOx). The layer-by-layer (LbL) films on the ferrocene microcrystal followed by
      anti-insulin antibody sensitization were employed for the biolabled ferrocene
      microcapsules production. The antibody sensitized ferrocene microcapsules worked
      as a probe in the proposed system. The microcapsules provided a higher signal
      generating molecule to antibody (S/P) ratio of 4.52x10(6) to 12.4x10(6).
      Microcapsules with different antibody loads (388-1070 antibody molecules per
      capsule) were subjected to a solid-phase immunoassay for the detection of
      insulin. The microcapsule having 1030 anti-insulin antibody molecules per capsule
      demonstrated good performance for insulin determination. The calibration curve
      for insulin had a linear range of 10(-10) to 10(-7) g mL(-1) with R(2)=0.990,
      3.9% R.S.D. The limit of detection for insulin was 10 pg mL(-1) of 100 microL
      sample (equivalent to 10(-12)g of insulin). The determination range for the
      glucose was 0.5 and 40 mM with R(2)=0.996 and 4.1% R.S.D.

PMID- 16950611
TI  - DNA single-base mismatch study with an electrochemical enzymatic genosensor.
AB  - A thorough selectivity study of DNA hybridization employing an electrochemical
      enzymatic genosensor is discussed here. After immobilizing on a gold film a 30
      mer 3'-thiolated DNA strand, hybridization with a biotinylated complementary one
      takes place. Then, alkaline phosphatase is incorporated to the duplex through the
      interaction streptavidin-biotin. Enzymatic generation of indigo blue from 3
      indoxyl phosphate and subsequent electrochemical detection was made. The
      influence of hybridization conditions was studied in order to better discern
      between fully complementary and mismatched strands. Detection of 3, 2 and 1
      mismatch was possible. The type and location of the single-base mismatch, as well
      as the influence of the length of the strands was studied too. Mutations that
      suppose displacement of the reading frame were also considered. The effect of the
      concentration on the selectivity was tested, resulting a highly selective
      genosensor with an adequate sensitivity and stability.

PMID- 16950612
TI  - Layer-by-layer hydroxymethyl ferrocene modified sensor for one-step flow/stop
      flow injection amperometric immunoassay of alpha-fetoprotein.
AB  - A rapid one-step flow/stop-flow injection amperometric immunoassay for alpha
      fetoprotein (AFP) using a novel home-produced electrochemical sensor was
      proposed. The sensor was prepared using layer-by-layer adsorption of positively
      charged poly(allylamine) (PAA) and negatively charged hydroxymethyl ferrocene on
      a screen-printed electrode (SPE). The electrochemistry of the immobilized
      ferrocene moieties showed a surface-controlled electrode process. Based on an
      electrochemical enzyme-linked immunoassay with the immobilized ferrocene moieties
      as an electron transfer mediator between the electrode and the horseradish
      peroxidase (HRP)-labeled anti-AFP antibody, a calibration curve with two linear
      ranges from 5 to 20 and 20 to 150 ng ml-1 and a detection limit of 2 ng ml-1 for
      AFP determination was obtained under the optimized conditions of 0.891 ml min-1
      flow rate, 20 microl injection volume and +25 mV applied potential. The sensor
      showed good repeatability and reproducibility and retained more than 95% of its
      original signal after 15 days of storage. The proposed method eliminated the need
      for washing and addition of any substrate or mediator. The complete assay could
      be handled in less than 25 min with a one-step injection of a 40 microl sample
      solution. The proposed method would be valuable for the diagnosis and monitoring
      of carcinoma and its metastasis.

PMID- 16950613
TI  - Anesthetic management of a pregnant patient with dengue hemorrhagic fever for
      emergency cesarean section.
AB  - Dengue fever is the most common and widespread insect-borne viral infection
      worldwide. The most critical phase of this viral infection is the defervescent
      phase when the fever subsides but the patient develops life-threatening
      thrombocytopenia due to complement activation by viral antigens binding to
      platelets. We have outlined the anesthetic management of a 25-year-old
      primigravida with dengue hemorrhagic fever who needed to undergo emergency
      cesarean section. We also describe this illness in brief and compare the
      anesthetic management to that of preeclampsia and hemolysis, elevated liver
      enzymes and low platelet syndrome which this disease mimics.

PMID- 16950614
TI  - Association of ABCB1 genotypes with paclitaxel-mediated peripheral neuropathy and
      neutropenia.
AB  - Here, we evaluated the relationships between ABCB1 (P-glycoprotein, MDR1)
      polymorphisms and paclitaxel (Taxol)-induced toxicity and pharmacokinetics.
      Twenty-six patients were assessable for pharmacogenetics and pharmacokinetics, 22
      for neurotoxicity and 18 for myelotoxicity. Patients carrying two reference
      alleles for the ABCB1 3435C>T polymorphism trended toward a reduced risk to
      develop neuropathy as compared to patients carrying at least one variant allele
      (P=0.09). Additionally, patients who were homozygous variant at the 2677 and 3435
      loci had a significantly greater percent decrease in absolute neutrophil count at
      nadir (P=0.02). Neither polymorphism correlated with paclitaxel pharmacokinetics.
      This pilot study suggests that paclitaxel-induced neuropathy and neutropenia
      might be linked to inherited variants of ABCB1 through a mechanism that is
      unrelated to altered plasma pharmacokinetics.

PMID- 16950615
TI  - Tissue inhibitor of metalloproteinase-3 induces apoptosis in prostate cancer
      cells and confers increased sensitivity to paclitaxel.
AB  - Prostate cancer is the most common cancer and the second leading cause of cancer
      related death in American men. To investigate the possible usefulness of tissue
      inhibitor of metalloproteinase-3 (TIMP-3) in prostate cancer gene therapy, we
      used an adenovirus expressing TIMP-3 to assess its role as an apoptosis trigger
      in highly metastatic prostate cancer cell lines PC-3 and DU-145. We showed that
      TIMP-3 alone induced apoptotic cell death which was triggered by mitochondrion
      mediated caspase-3 activation. In combination treatment, we found that adenovirus
      mediated expression of TIMP-3 greatly sensitised prostate cancer cells to
      chemotherapeutic drug paclitaxel, indicating a superadditive or synergistic
      effect of TIMP-3 and cytostatic treatment on prostate cancer cell death. The
      proper combination of adenovirus-mediated expression of TIMP-3 with conventional
      chemotherapeutic drug(s) could have potential benefits in treating highly
      metastatic prostate cancer.

PMID- 16950616
TI  - Facial nerve function in carcinoma of the parotid gland.
AB  - AIM: To analyse, for patients with carcinoma of the parotid gland, the prognostic
      value for treatment outcome of the function of the facial nerve (NVII), and
      determining facial nerve dysfunction after treatment. METHODS AND MATERIALS: In a
      retrospective study of the Dutch head and Neck cooperative group (NWHHT), data of
      324 patients with parotid carcinoma were analysed. The function of N VII before
      treatment was intact in 77%, partially and completely impaired in 14% and 7%,
      respectively. Eighty-eight percent of the patients were treated surgically, and
      77% of them were treated by a combination of postoperative radiotherapy. In 21%
      NVII was sacrificed, a reconstruction was performed in one of three. RESULTS:
      Independent risk factors for N VII dysfunction before treatment were tumour
      localisation, positive neck nodes at presentation, pain, increasing age, and
      perineural invasion. Regional, not local, control was significantly impaired for
      complete facial paralysis. N VII dysfunction was an independent factor for
      disease free survival, and was 69%, 37% and 13% for normal, partially and
      completely impaired function, respectively. After treatment 22% of the patients
      experienced a partial paralysis, and 13% of the patients experienced a complete
      paralysis of N VII. CONCLUSION: For patients with parotid carcinoma, facial nerve
      function before treatment is a strong prognostic factor for disease free
      survival.

PMID- 16950617
TI  - N',2-diphenylquinoline-4-carbohydrazide based NK3 receptor antagonists II.
AB  - Introduction of selected amine containing side chains into the 3-position of N',2
      diphenylquinoline-4-carbohydrazide based NK3 antagonists abolishes unwanted hPXR
      activation. Introduction of a fluorine at the 8-position is necessary to minimize
      unwanted hI(Kr) affinity and a piperazine N-tert-butyl group is necessary for
      metabolic stability. The lead compound (8m) occupies receptors within the CNS
      following oral dosing (Occ(90) 7 mg/kg po; plasma Occ(90) 0.4 microM) and has
      good selectivity and excellent PK properties.

PMID- 16950618
TI  - Synthesis and antiproliferative activity of (2R,3R)-disubstituted
      tetrahydropyrans.
AB  - In this study, we synthesized a series of enantiomerically pure (2R,3R)
      disubstituted tetrahydropyrans with diverse functional groups. The in vitro
      antiproliferative activities were examined in the human solid tumor cell lines
      A2780 (ovarian cancer), SW1573 (non-small cell lung cancer), and WiDr (colon
      cancer). Overall, the results show the relevance for antiproliferative activity
      of the alpha,beta-unsaturated ester side chain at position 2 of the THP ring.

PMID- 16950619
TI  - Inhibition of P-glycoprotein-mediated multidrug efflux by aminomethylene and
      ketomethylene analogs of reversins.
AB  - Several aminomethylene analogs and a ketomethylene analog of reversins were
      synthesized in order to evaluate their ability to inhibit P-glycoprotein-mediated
      drug efflux in K562/R7 human leukemic cells overexpressing P-glycoprotein. These
      analogs retained good activity compared to cyclosporin A and the original
      reversins.

PMID- 16950620
TI  - N',2-diphenylquinoline-4-carbohydrazide based NK3 receptor antagonists.
AB  - A new class of potent NK3R antagonists based on the N',2-diphenylquinoline-4
      carbohydrazide core is described. In an ex vivo assay in gerbil, the lead
      compound 2g occupies receptors within the CNS following oral dosing (Occ(90) 30
      mg/kg po; plasma Occ(90) 0.95 microM) and has good selectivity and promising PK
      properties.

PMID- 16950621
TI  - Novel imidazole-based combretastatin A-4 analogues: evaluation of their in vitro
      antitumor activity and molecular modeling study of their binding to the
      colchicine site of tubulin.
AB  - The in vitro antitumor activity of novel combretastatin-like 1,5- and 1,2-diaryl
      1H-imidazoles was evaluated against the NCI 60 human tumor cell lines panel.
      Compounds 2d and 2g proved to be more cytotoxic than CA-4 in tests involving
      their evaluation over a 10(-4)-10(-8) range. Docking experiments showed a good
      correlation between the MG_MID Log GI(50) values of all these compounds and their
      calculated interaction energies with the colchicine binding site of alphabeta
      tubulin.

PMID- 16950622
TI  - Synthesis of radiolabeled stilbene derivatives as new potential PET probes for
      aryl hydrocarbon receptor in cancers.
AB  - New carbon-11 and fluorine-18 labeled stilbene derivatives, cis-3,5-dimethoxy-4'
      [11C]methoxystilbene (4'-[11C]8a), cis-3,4',5-trimethoxy-3'-[11C]methoxystilbene
      (3'-[11C]8b), trans-3,5-dimethoxy-4'-[11C]methoxystilbene (4'-[11C]10a), trans
      3,4',5-trimethoxy-3'-[11C]methoxystilbene (3'-[11C]10b), cis-3,5-dimethoxy-4'
      [18F]fluorostilbene (4'-[18F]12a), and trans-3,5-dimethoxy-4'-[18F]fluorostilbene
      (4'-[18F]13a), were designed and synthesized as potential PET probes for aryl
      hydrocarbon receptor (AhR) in cancers.

PMID- 16950623
TI  - Synthesis and free radical scavenging activity of a novel metabolite from the
      fungus Colletotrichum gloeosporioides.
AB  - A novel metabolite (-)-1 was isolated as its peracetylated derivative, (-)-2
      (3',4'-diacetoxyphenyl)-3,4-diacetoxytetrahydrofuran (2), from a strain of the
      phytopathogenic fungus Colletotrichum gloeosporioides CECT 20122. The synthesis
      of (-)-1 was carried out by ring-closing metathesis of diene 6 and
      stereoselective dihydroxylation of a dihydrofuran derivative 7 as key steps. The
      tetraol (-)-1 showed free radical scavenging activity comparable to that of BHT,
      caffeic acid or protocatechuic acid.

PMID- 16950624
TI  - SER-HIS-ASP catalytic triad in model non-aqueous solvent environment: a
      computational study.
AB  - Emerging new properties and applications of enzymes in organic solvents and ionic
      liquids are unabating. By applying a combined Quantum Mechanics/Continuum
      Mechanics computation on a prototypical catalytic triad serine-histidine
      aspartate (SER-HIS-ASP) interacting with ethanol or acetonitrile molecules, the
      major difference between protic and aprotic solvents in effecting transition
      state stabilization has been analyzed. Moderately polar aprotic solvent
      acetonitrile is predicted to be unable to stabilize the transition state in
      replacing the role of the oxyanion-hole environment, whereas protic ethanol
      solvent molecules of similar polarity to acetonitrile are adequate in re-gaining
      the enzymatic activities.

PMID- 16950625
TI  - Morphological characterization of the anuran integument of the Proceratophrys and
      Odontophrynus genera (Amphibia, Anuran, Leptodactylidae).
AB  - The morphological characteristics of the leptodactylid integument of
      Proceratophrys and Odontophrynus genera were investigated by means of
      stereoscopic, low vacuum scanning electron and light microscopy. The integument
      surface of Proceratophrys boiei, Proceratophrys laticeps and Proceratophrys
      appendiculata exhibited several projections, while the integument of
      Odontophrynus americanus had rounded elevations with smooth profile. Light
      microscopic observations showed the basic integument morphology for all anurans,
      i.e., an epidermis and a dermis, which is subdivided into a spongious layer and a
      compact layer. The epidermis is formed by basal, intermediary and cornified
      layers. However, in Proceratophrys genus the cornified layer had an irregular
      outline, while in O. americanus the external surface was smooth. In the spongious
      dermis, mucous and venom exocrine glands were observed, but in O. americanus an
      exclusive glandular type with apocrine secretory pattern was identified. The
      integument morphology showed peculiar characteristics that may be helpful for
      genus distinction. Thus, morphological methods may be considered as an efficient
      means to characterize and to differentiate anuran genera.

PMID- 16950626
TI  - Polarization phase in aberration compensation.
AB  - A phase/amplitude mask on the aperture of an imaging system results in a pupil
      function that is multiplicative with the lens function, resulting in a
      morphological transformation of the imaging wavefront. It was shown that such
      amplitude and phase functions can be implemented using polarization masks, with
      the advantage that the phase and amplitude can be controlled in real time and in
      some cases, independently of each other. The phase and amplitude variation over
      the mask can be controlled either by changing the polarization of the mask or by
      changing the input beam parameters. Wavefront tailoring using polarization-masked
      apertures is therefore feasible and may be utilized for focal shift and partial
      aberration compensation. For complete compensation of aberration, the phase
      distribution over the mask should be conjugate to that of the phase error of the
      aberrant wavefront, which necessitates the use of a continuously variable
      polarization mask. Since such a mask is difficult to implement, we have
      considered polarizing masks consisting of discrete polarized zones on the lens
      aperture, leading to polarization phase steps on the exit pupil of the imaging
      system. The simulation results presented in this paper show that effects of focal
      shift, partial compensation of primary spherical aberration and astigmatism can
      indeed be achieved by the proper use of polarization masked apertures.

PMID- 16950628
TI  - The European Working Time Directive: quo vadis? A well-planned and organized
      assassination of surgery.

PMID- 16950627
TI  - Induction of multiple heat shock proteins and neuroprotection in a primary
      culture model of familial amyotrophic lateral sclerosis.
AB  - High threshold for stress-induced activation of the heat shock transcription
      factor, Hsf1, may contribute to vulnerability of motor neurons to disease and
      limit efficacy of agents promoting expression of neuroprotective heat shock
      proteins (Hsps) through this transcription factor. Plasmid encoding a
      constitutively active form of Hsf1, Hsf1act, and chemicals shown to activate Hsf1
      in other cells were investigated in a primary culture model of familial
      amyotrophic lateral sclerosis. Hsf1act and the Hsp90 inhibitor, geldanamycin,
      induced high expression of multiple Hsps in cultured motor neurons and conferred
      dramatic neuroprotection against SOD1G93A in comparison to Hsp70 or Hsp25 alone.
      Two other Hsp90 inhibitors, 17-allylamino-17-demethoxygeldanamycin (17-AAG) and
      radicicol, and pyrrolidine dithiocarbamate induced robust expression of Hsp70 and
      Hsp40 in motor neurons, but at cytotoxic concentrations. 17-AAG, which penetrates
      the blood-brain barrier, has exhibited a higher therapeutic index than
      geldanamycin, but this may not be the case when activation of Hsf1 in neurons is
      targeted.

PMID- 16950629
TI  - Survival in elderly patients with severe aortic stenosis is dramatically improved
      by aortic valve replacement: Results from a cohort of 277 patients aged > or =80
      years.
AB  - BACKGROUND: Calcific aortic stenosis (AS) is a disease of the elderly. However,
      there is reluctance to offer aortic valve replacement (AVR) for elderly patients
      with severe AS. We investigated if AVR confers a survival benefit in elderly
      patients with severe AS. METHODS: We screened our echocardiographic database from
      1993 to 2003 for patients with severe AS (AV area < or = 0.8 cm2) and age > or
      =80 years. Two hundred and seventy seven patients were identified. Complete chart
      reviews were performed for clinical data. Mortality data were obtained from
      National Death Index. Survival curves of patients who underwent AVR during the
      follow-up period were compared with those managed nonsurgically. RESULTS: Patient
      characteristics were as follows: age 85+/-4 years, 53% male, AV area 0.68+/-0.16
      cm2, EF 52+/-20%, CAD 47%, diabetes 17%. Over a mean follow-up of 2.5 years, 55
      (20%) had AVR and there were 175 deaths. One-year, 2-year and 5-year survival
      rates among patients with AVR were 87, 78 and 68% respectively, compared with 52,
      40 and 22%, respectively, in those who had no AVR (p < 0.0001). Hazard ratio for
      death with AVR adjusted for 19 covariates including age, EF, gender,
      comorbidities and pharmacotherapy was 0.38 (95% CI 0.26-0.66, p < 0.0001).
      CONCLUSION: Prognosis of medically managed severe calcific AS in the elderly
      patients is dismal. AVR appears to improve survival of these patients and should
      be strongly considered in the absence of other major comorbidities.

PMID- 16950630
TI  - Stentless and stented aortic valve replacement in elderly patients: Factors
      affecting midterm clinical and hemodynamical outcome.
AB  - OBJECTIVE: To report on the midterm results of aortic valve replacement (AVR)
      with stented and stentless bioprosthesis in an elderly population by analyzing
      the factors affecting survival and hemodynamical performance. METHODS: In a
      retrospective study, 145 patients with a Toronto stentless prosthesis are
      compared with 110 patients with a stented Carpentier-Edwards valve. The 5- to 10
      year clinical outcome, transprosthetic gradients, and early and late left
      ventricular mass (LVM) regression are analyzed in view of specific prosthesis-
      and patient-related factors. RESULTS: Actuarial survival at 5 years is 82% after
      stentless AVR versus 68% after stented AVR (p < 0.001) in elderly patients.
      However, there was no difference in survival at 8 years, being 55.9% and 59.5%,
      respectively. Univariate analysis revealed that advanced age at the time of
      operation, NYHA class IV, use of a stented xenograft, presence of patient
      prosthesis mismatch (PPM) (IEOA < or = 0.85 cm2/m2), and severe preoperative left
      ventricular (LV) hypertrophy (LVMI > 180 g/m2) affected survival adversely. But
      multivariate analysis determined only age, NYHA class IV and excessive LV
      hypertrophy as independent predictors of late mortality. Stented and stentless
      xenografts were equally effective in terms of transprosthetic gradients and LVMI
      regression. The use of a stentless valve significantly reduced the occurrence of
      PPM (18% vs 41%, p < 0.01). Early LVMI regression at 1 year was optimized by the
      avoidance of PPM, indicated by a higher absolute (43.7+/-28.3 g/m2 vs 58.6+/-33.8
      g/m2, p = 0.003) and relative (25.0+/-12.7% vs 31.4+/-14.9%, p=0.004) mass
      regression. However, late LV remodeling was predominantly affected by systemic
      hypertension and severe preoperative LV hypertrophy, resulting in the incomplete
      LVMI resolution in 61.3% and 66.7% of these patients, respectively. CONCLUSION:
      In elderly patients, aortic valve replacement appears to be equally effective
      with a stentless or stented bioprosthesis. Midterm clinical outcome is mainly
      determined by patient-related factors such as age, advanced NYHA class, and
      severity of preoperative LV hypertrophy. Regarding post-AVR left ventricular
      remodeling, patient-prosthesis mismatch influences the early phase, whereas
      arterial hypertension affects the late regression more. However, the left
      ventricular remodeling is continuously compromised by the preoperative presence
      of excessive hypertrophy, despite the efficacy of the aortic valve replacement.

PMID- 16950631
TI  - Aortic stenosis in the elderly: Rethinking strategies.

PMID- 16950632
TI  - Chemokine gene polymorphisms in idiopathic anterior uveitis.
AB  - OBJECTIVES: The aim of this study was to determine whether there are any
      associations between single nucleotide polymorphisms of the chemokine genes IL-8,
      MCP-1, their corresponding receptors CXCR1 and CCR2 and disease outcome in
      patients with acute idiopathic anterior uveitis. METHODS: 60 Caucasian patients
      with idiopathic acute recurrent anterior uveitis together with 120 healthy
      Caucasian control subjects were tested for the presence of 16 bi-allelic
      polymorphisms and HLA-B27 using polymerase chain reaction in association with
      sequence-specific primers with mismatches at the 3' end. The genetic data was
      then compared between patients and controls, and within the patient group itself
      for association with clinical disease outcome. RESULTS: As expected, the
      frequency of HLA-B27 was significantly higher in the patient group than the
      control group (63.33% versus 15.83%; Pearson's P<0.0001, Fisher's P<0.0001). In
      addition, the frequency of the T allele of MCP-1 63555 was found to be
      significantly higher in the control group when compared to the patient group
      (P=0.0160). CONCLUSION: This study describes an association between acute
      anterior uveitis and MCP-1 63555 polymorphisms where the T allele may be a
      protective marker against the disease.

PMID- 16950633
TI  - The influence of kainic acid on core temperature and cytokine levels in the
      brain.
AB  - Excitotoxic brain injury is associated with hyperthermia, and there are data
      showing beneficial effects of hypothermia on neurodegeneration and that
      hyperthermia facilitates the neurodegeneration. Cytokines are inflammatory
      proteins that seem to be involved in the neuroinflammation associated with
      epilepsy. Core temperature changes caused by the epileptogenic glutamate analogue
      kainic acid (KA) were investigated in relation to changes in levels of the pro
      inflammatory cytokines interleukin-1beta (IL-1beta) and interleukin-6 (IL-6), and
      the endogenous interleukin-1 receptor antagonist (IL-1ra). The temperature was
      measured every 10 min during the first hour, and at 90 and 120 min, and hourly
      until 8 h after KA-injection (10 mg/kg). The cytokines were measured in the
      hypothalamus, a site of temperature regulation, and in hippocampus, cerebellum,
      and frontal cortex. KA induced a brief hypothermia followed by hyperthermia. IL
      1beta levels were increased after KA-administration in all brain regions examined
      and, excepting hippocampus, returned to baseline levels at 24 h. The hippocampal
      IL-1ra levels were significantly increased at 24 h, whereas no changes in IL-6
      levels were observed. The changes in IL-1beta levels and in ratios between the
      levels of the three cytokines, may account for some of the temperature changes
      and the behavioural manifestations induced by KA.

PMID- 16950634
TI  - Cytokine gene polymorphisms and susceptibility to cutaneous leishmaniasis in
      Iranian patients.
AB  - Cutaneous Leishmaniasis (CL) is one of the most prevalent clinical forms of
      leishmaniasis. Preliminary data suggest that cytokine gene polymorphisms can
      contribute to resistance or susceptibility to CL. Therefore, we investigated the
      association of functional polymorphisms in four cytokine genes with
      susceptibility to, and clinical outcome of CL. A total of 201 patients with self
      healing cutaneous leishmaniasis (SCL) and 92 asymptomatic infected controls (AIC)
      from Fars province as well as 58 patients with chronic cutaneous leishmaniasis
      (CCL) and their 688 normal controls (normal Iranian population or NIP) who were
      collected from the different areas of Iran were included in the study. The allele
      specific oligonucleotide polymerase chain reaction (ASO-PCR) or PCR-RFLP
      (restriction fragment length polymorphism) methods were used for genotyping. The
      frequency of TNF-alpha -308 G-->A and TNF-beta +252 G-->A gene polymorphisms were
      not different between studied groups. Distribution of IFN-gamma +874 A-->T and IL
      4 -590 C-->T polymorphism were also compared between SCl or CCL patients and
      their controls. IFN-gamma +874 A-->T polymorphism was less common in CCL patients
      compared to the NIP (chi(2)=12.53, p=0.0019). Significant differences in
      frequency of IL-4 -590 C -->T polymorphism were also found between the SCL and
      AIC (chi(2)=8.64, p=0.003). In conclusion, our results suggest that functional
      genetic variants in the IL-4 promoter could influence the risk of developing CL
      while the polymorphism in the first intron of the IFN-gamma gene might influence
      the progression of disease towards CCL.

PMID- 16950635
TI  - Expression and purification of a trivalent pertussis toxin-diphtheria toxin
      tetanus toxin fusion protein in Escherichia coli.
AB  - Pertussis toxoid, diphtheria toxoid, and tetanus toxoid are key components of
      diphtheria-tetanus-acellular pertussis vaccines. The efficacy of the vaccines is
      well documented, however, the vaccines are expensive partly because the antigens
      are derived from three different bacteria. In this study, a fusion protein (PDT)
      composed of the immunoprotective S1 fragment of pertussis toxin, the full-length
      non-toxic diphtheria toxin, and fragment C of tetanus toxin was constructed via
      genetic means. The correct fusion was verified by restriction endonuclease
      analysis and Western immunoblotting. Escherichia coli carrying the recombinant
      plasmid (pCoPDT) produced a 161kDa protein that was recognized by antibodies
      specific to the three toxins. The expression of the PDT protein was inducible by
      isopropyl-beta-d-thio-galactoside but the total amount of protein produced was
      relatively low. Attempts to improve the protein yield by expression in an E. coli
      strain (Rosetta-gami 2) that could alleviate rare-codon usage bias and by
      supplementation of the growth media with amino acids deemed to be a limiting
      factor in translation were not successful. The PDT protein remained in the
      insoluble fraction when the recombinant E. coli was grown at 37 degrees C but the
      protein became soluble when the bacteria were grown at 22 degrees C. The PDT
      protein was isolated via affinity chromatography on a NiCAM column. The protein
      was associated with five other proteins via disulfide bonds and non-covalent
      interactions. Following treatment with beta-mercaptoethanol, the PDT fusion was
      purified to homogeneity by preparative polyacrylamide gel electrophoresis with a
      yield of 45 microg/L of culture. Antisera generated against the purified PDT
      protein recognized the native toxins indicating that some, if not all, of the
      native epitopes were conserved.

PMID- 16950636
TI  - Bcl-2 proteins link programmed cell death with growth and morphogenetic
      adaptations in the fungal plant pathogen Colletotrichum gloeosporioides.
AB  - Proteins belonging to the Bcl-2 family regulate apoptosis in mammals by
      controlling mitochondria efflux of cytochrome c and other apoptosis-related
      proteins. Homologues of human Bcl-2 proteins are found in different metazoan
      organisms where they play a similar role, while they seem to be absent in plants
      and fungi. Nonetheless, Bcl-2 protein members can induce or prevent yeast cell
      death, suggesting that enough functional conservation exists between apoptotic
      machineries of mammals and fungi. Here we show that induction or prevention of
      apoptosis by Bcl-2 proteins in the fungal plant pathogen Colletotrichum
      gloeosporioides is tightly linked with growth and morphogenetic adaptation that
      occur throughout the entire fungal life cycle. Isolates expressing the pro
      apoptotic Bax protein underwent cell death with apoptotic characteristics, and
      showed alterations in conidial germination that are associated with pathogenic
      and non-pathogenic life styles. Isolates expressing the anti-apoptotic Bcl-2
      protein had prolonged longevity, were protected from Bax-induced cell death, and
      exhibited enhanced stress resistance. These isolates also had enhanced mycelium
      and conidia production, and were hyper virulent to host plants. Our findings show
      that apoptotic-associated machinery regulates morphogenetic switches, which are
      critical for proper responses and adaptation fungi to different environments.

PMID- 16950637
TI  - Physiology of temperature regulation: comparative aspects.
AB  - Few environmental factors have a larger influence on animal energetics than
      temperature, a fact that makes thermoregulation a very important process for
      survival. In general, endothermic species, i.e., mammals and birds, maintain a
      constant body temperature (Tb) in fluctuating environmental temperatures using
      autonomic and behavioural mechanisms. Most of the knowledge on thermoregulatory
      physiology has emerged from studies using mammalian species, particularly rats.
      However, studies with all vertebrate groups are essential for a more complete
      understanding of the mechanisms involved in the regulation of Tb. Ectothermic
      vertebrates-fish, amphibians and reptiles-thermoregulate essentially by
      behavioural mechanisms. With few exceptions, both endotherms and ectotherms
      develop fever (a regulated increase in Tb) in response to exogenous pyrogens, and
      regulated hypothermia (anapyrexia) in response to hypoxia. This review focuses on
      the mechanisms, particularly neuromediators and regions in the central nervous
      system, involved in thermoregulation in vertebrates, in conditions of euthermia,
      fever and anapyrexia.

PMID- 16950638
TI  - Inborn errors of isoleucine degradation: a review.
AB  - Three inborn errors have been identified in the pathway of isoleucine
      degradation. Deficiency of beta-ketothiolase (beta-KT, also known as T2,
      mitochondrial acetoacetyl-CoA thiolase and acetyl-CoA acetyltransferase 1) is a
      well-described disorder which presents with acute episodic ketoacidosis. In
      contrast, short/branched-chain acyl-CoA dehydrogenase (SBCAD) and 2-methyl-3
      hydroxybutyryl-CoA dehydrogenase (MHBD) deficiencies are recently described and
      relatively rare defects which present with predominantly neurological
      manifestations, although acute metabolic decompensation may occur in the early
      newborn period. Careful examination of urine organic acids is required for
      identification and differential diagnosis of these disorders, with awareness that
      the abnormalities may be subtle and variable. Tandem MS analysis of
      acylcarnitines may reveal elevated C5 (SBCAD) or C5:1 and/or OH-C5 species (MHBD
      and beta-KT deficiencies) but the abnormalities are non-diagnostic and may be
      intermittent or absent. Confirmation of diagnosis is therefore advisable by
      specific enzyme assay and/or mutation analysis of the ACAT1 (beta-KT), ACADSB
      (SBCAD) or HADH2 (MHBD) genes. The latter is located on the X chromosome,
      accounting for the milder clinical phenotype in females. If beta-KT deficiency is
      diagnosed early and treated by fasting avoidance and modest protein restriction,
      ketoacidosis episodes can be prevented and the prognosis is excellent. The role
      of treatment in SBCAD deficiency remains unclear pending further delineation of
      its clinical phenotype and pathogenicity, particularly regarding asymptomatic
      individuals detected by expanded newborn screening. The ineffectiveness of
      isoleucine restriction in MHBD deficiency is consistent with the additional roles
      of this multifunctional enzyme in sex steroid and neurosteroid metabolism and its
      interaction with amyloid-beta peptide.

PMID- 16950639
TI  - Crusted scabies (sarcoptic mange) in four cats due to Sarcoptes scabiei
      infestation.
AB  - Four new cases of sarcoptic mange in cats are described. Two cats resided in
      areas known to be frequented by foxes, another cohabited with a dog recently
      diagnosed with sarcoptic mange, while the final cat lived with a mixed breed dog
      that had been treated for sarcoptic mange 7 months previously. Three cases were
      diagnosed on the basis of characteristic mite size and morphology in skin
      scraping from representative lesions, situated on the head (two cases) or head
      and distal hind limbs (one case). Mites were highly mobile and abundant in all
      instances, and easily detected also in skin biopsy specimens procured from two
      cases. Eosinophilic inflammation, hyperkeratosis and parakeratosis were prominent
      in the tissue sections. In the remaining case, the diagnosis was presumptive,
      based on characteristic lesions, cohabitation with a canine scabies patient and
      positive response to scabicide therapy. Pruritus was not a prominent clinical
      feature in any patient and was considered to be absent in three of the four
      cases. Lesions in three cats with long-standing disease were reminiscent of
      crusted scabies (synonym: Norwegian scabies, parakeratotic scabies) as seen in
      human patients. In three cases, in-contact human carriers developed itchy
      cutaneous papular lesions. Two cases responded promptly to therapy with systemic
      avermectin drugs, while one responded to topical treatment with lime sulphur and
      the remaining cat received both a lime sulphur rinse and ivermectin. Sarcoptic
      mange should be considered in the differential diagnosis of cats with non
      pruritic crusting skin diseases, especially when there is contact with foxes or
      dogs, and when owners have itchy papular lesions.

PMID- 16950640
TI  - Epidemiology of meningitis in Al-Ain, United Arab Emirates, 2000-2005.
AB  - OBJECTIVE: To describe the epidemiologic features of meningitis in Al-Ain Medical
      District, United Arab Emirates from January 2000 through June 2005. METHODS: A
      retrospective review of clinical records and notification forms for cases of
      meningitis reported to the Department of Preventive Medicine, Al-Ain. Data
      collected and compiled included demographic features, causative microbiologic
      agents, and annual incidence rates of meningitis, by etiology. RESULTS: Ninety
      two cases of meningitis were reported during the study period; 53% were bacterial
      and 37% were viral in origin. Neisseria meningitidis was the leading bacterial
      pathogen (35%) followed by Streptococcus pneumoniae (16%). Ten percent of
      clinically diagnosed cases of meningitis had no causative microorganism
      recovered, and in 33% of patients with presumed pyogenic meningitis no specific
      bacterial pathogen could be identified. The peak occurrence of meningitis was in
      young children less than one year old. Most cases of meningococcal meningitis
      were seen among prison inmates and laborers, while viral meningitis occurred
      mainly in children and young adults attending school. The incidence rate of
      meningitis in Al-Ain ranged between 2.2/100,000 population in 2000 and 1/100,000
      in 2005, with an overall downward trend by year. The incidence of Haemophilus
      influenzae type b decreased significantly after implementation of the national
      immunization program in 1999. CONCLUSIONS: Improved methods of bacterial
      detection including isolate serotyping must be made available in order to further
      reduce mortality and morbidity from meningitis.

PMID- 16950641
TI  - [Use of PET for evaluation of treatment response in oncology].
AB  - 18FDG -PET is now usually included in the treatment strategy, for the staging or
      the diagnosis of recurrence. In lymphoma, PET is well documented for evaluation
      of tumour response. For solid tumours, despite good published results, the
      accuracy of PET has to be confirmed by large series of patients. A good
      interpretation of PET needs a SUV analysis. New radiotraceurs of the nuclear
      synthesis could certainly improve the accuracy of response evaluation by PET.

PMID- 16950642
TI  - [How to improve ART results? Is France behind other countries? Strategy for
      single embryo transfer: The value of embryo selection and embryo freezing].
AB  - Multiple embryo transfer is associated with a high frequency of twin pregnancies
      with costly complications involving both mother and child. As a result high
      priority is currently being given to the development of single embryo transfer
      (SET) programs. France seems to be lagging behind Northern European countries in
      the development of SET and widespread use of SET will depend on convincing
      physicians that this policy will not have a negative impact on success rate, as
      has been the case for many protocols described in the literature as well as in
      our own experience. Our SET program includes patients less than 36 years of age
      undergoing their first FIV-ICSI. If two embryos showing satisfactory morphology
      are obtained, one is selected transferred and the other is systematically frozen.
      Selection for transfer is based on two criteria, i.e. observation of even early
      cleavage 26 hours after FIV-ICSI and evaluation of embryo morphology score on day
      2. Embryo morphology score is based on the presence of four blastomeres and
      absence of blastomere irregularities and anucleated fragmentation. Last, a
      prerequisite for SET is an effective freezing program. A pregnancy rate of 13%
      per thawing was sufficient enough to obtain a cumulative pregnancy rate after SET
      (N = 205) and subsequent frozen embryo transfer (FET) similar to the cumulative
      pregnancy rate obtained after double embryo transfer (N = 394) and subsequent FET
      (46.3 vs 46.7%, NS). Twin delivery rate were respectively 2,6% after SET and
      26,6% after double embryo transfer (P < 0.01).

PMID- 16950643
TI  - [Endometriosis in teenagers].
AB  - Endometriosis has long been considered as a disease of women over 30 years old.
      However, recent data from the literature demonstrated its high incidence in
      teenagers. Endometriosis in teenagers is generally associated with chronic pelvic
      pains and cyclical signs are less common than in adults. The persistence of the
      pain despite an estroprogestative contraception associated with non-steroidal
      anti-inflammatory drugs is a strong argument for the diagnosis and justifies a
      laparoscopic exploration. During this laparoscopy, the search for atypical
      lesions, which are much more common than typical ones, is essential. Biopsies of
      these lesions is mandatory in every patient to rule out false positives and false
      negatives which are common in atypical lesions. The aim of the treatment is to
      improve the pain. The first line of medical treatment is based on the
      estroprogestative contraception and non-steroidal anti-inflammatory drugs. The
      prescription of GnRH should be the ultimate solution because the bone reserve
      increases until the age of 18 to 20. The laparoscopic treatment, when required,
      should be as complete as possible. Early diagnosis and medical management may
      prevent the development of the disease. However, further studies in the teenager
      are essential to improve the current empirical management.

PMID- 16950644
TI  - Different roles of protein kinase C-betaI and -delta in the regulation of
      adipocyte differentiation.
AB  - Protein kinase C (PKC) is a member of serine/threonine protein kinase family that
      plays important roles in the control of vast variety of cellular functions.
      Nevertheless, the regulatory effect of PKC on adipogenesis remained not well
      understood. In this study, we investigated the effect of several PKC isoforms on
      the adipogenic conversion of 3T3-L1 preadipocytes induced by dexamethasone,
      isobutylmethylxanthine and insulin. Treatment of cells with broad-spectrum PKC
      inhibitor Ro318220 suppressed the adipogenesis. Go6976, a selective inhibitor for
      PKC isoforms-alpha, -betaI and -mu, also inhibited the adipogenesis of cells.
      Pretreatment of cells with peroxisomal proliferator activated receptor-gamma
      (PPARgamma) agonist troglitazone abolished the inhibitory effect of Go6976 on
      adipogenesis. The plasmic membrane translocation of PKC-betaI was observed at the
      first 2 days of differentiation. Whereas no translocation of PKC-alpha and -mu
      was observed. Overexpression of dominant negative PKC-betaI, but not wild-type
      PKC-betaI, blocked adipogenesis. This effect of dominant negative PKC-betaI can
      be reversed by troglitazone, suggesting that PKC-betaI is required for the
      initiation of adipogenesis. In addition, rottlerin, a specific inhibitor of PKC
      delta, can reverse the suppression of adipogenesis mediated by 12-O-tetradecanoyl
      phorbol-13-acetate, transforming growth factor-beta1, and epidermal growth
      factor. These data suggest that PKC-betaI is important in the induction of
      adipogenesis, while the PKC-delta has an inhibitory role for adipogenesis.

PMID- 16950645
TI  - Complexation of quercetin with three kinds of cyclodextrins: an antioxidant
      study.
AB  - The slightly water-soluble flavonoid quercetin (QUE) and its inclusion with
      either beta-cyclodextrin (betaCD), hydroxypropyl-beta-cyclodextrin (HP-betaCD) or
      sulfobutyl ether-beta-cyclodextrin (SBE-betaCD) were investigated. The
      stoichiometric ratios and stability constants describing the extent of formation
      of the complexes have been determined by phase-solubility measurements; in all
      cases type-A(L) diagrams have been obtained (soluble 1:1 complexes). The results
      showed that the inclusion ability of betaCD and its derivatives was the order:
      SBE-betaCD>HP-betaCD>betaCD. Kinetic studies of DPPH with QUE and CDs complexes
      were done. The results obtained indicated that the QUE-SBE-betaCD complex was the
      most reactive form. The scavenging capability of QUE and CDs complexes with DPPH
      and galvinoxyl was studied using ESR spectroscopy. All complexes showed a higher
      scavenging capability with both radicals, compare quercetin in water. Beside,
      these results indicated that the complexes formed maintained the quercetin
      antioxidant activity.

PMID- 16950646
TI  - X-ray crystal structure of phenylglycine hydrazide: synthesis and spectroscopic
      studies of its transition metal complexes.
AB  - Phenylglycine hydrazide was synthesized and investigated by X-ray
      crystallography. It crystallizes in the monoclinic space group P121/c with cell
      parameters a=5.9459 (18) Angstrom, b=5.1940 (16) Angstrom, c=26.7793 (83)
      Angstrom and Z=2. Its conformational changes, on complexation with transition
      metal ions Cu(II), Co(II), Ni(II), Mn(II) and Zn(II) has been studied on the
      basis of elemental analysis, magnetic moment and spectral (IR, (1)H NMR, UV-vis)
      studies. The bidentate nature of the ligand was confirmed on the basis of a
      comparative IR and NMR spectral studies. The trigonal bipyramidal geometries were
      observed for Cu(II), Ni(II) and Co(II) complexes, while it is octahedral for the
      remaining complexes. The conductivity data suggest them to be non-electrolytes.

PMID- 16950647
TI  - A short hydrogen bond investigation by polarized Raman spectra of Co2+ and Zn2+
      salts of pyromellitic acid.
AB  - Cobalt and zinc salts of 1,2,4,5-benzenetetracarboxylic acid (pyromellitic acid),
      [C(6)H(2)(COO)(4)H(4)], have been synthesized and investigate by polarized Raman
      spectroscopy. These compounds present short intramolecular hydrogen bonds (SHB)
      between adjacent carboxyl groups. Raman spectra indicate the presence of this
      interaction in both salts. Three specific vibrational of SHB modes have been
      investigated: O-H-O symmetric [nu(sym)(OHO)] and asymmetric [nu(asym)(OHO)]
      stretching modes and O-H stretching mode [nu(O-H)], which they were observed
      around 300, 850 and 2500 cm(-1), respectively. In crystallographic point of view,
      the cobalt salt presents a symmetric SHB while the zinc salt presents an
      asymmetric SHB. In cobalt salt all three vibrational modes of O-H-O groups in
      polarized Raman spectra occur in A(g) orientation although in zinc salts two of
      them are observed in A(g) orientation and one in B(g). Spectra analysis indicate
      that nu(sym)(OHO) mode is observed as A(g) to cobalt salt and B(g) to zinc salt.
      This mode occurs in a crowded spectral region and its identification was made by
      deconvolution techniques. Comparing spectra of the two salts, it is observed a
      small difference in relative intensity and wavenumber shift of nu(sym)(OHO)
      (deviance of 43 cm(-1)) and nu(OH) (deviance of 21 cm(-1)) modes due probably to
      differences in O...O distance between salts and in orientation of pyromellitate
      anion in unit cell. The nu(asym)(OHO) mode does not present significant
      wavenumber shift due difference in SHB. The nu(OH) band presents a great
      potential for hydrogen bond studies due to the fact that in its vibrational
      region (around 2500 cm(-1)) it is not observed other vibrational modes of these
      compounds.

PMID- 16950648
TI  - EPR of gamma-irradiated single crystals of 2-amino-5-nitro pyridinium L-tartrate:
      a NLO material.
AB  - Single crystals of a non-linear optical (NLO) material 2-amino-5-nitropyridinum L
      tartrate (ANPLT) were grown by solvent evaporation technique and characterized by
      the measurement of density, FT-IR, FT-Raman and X-ray diffraction techniques.
      Microhardness study and SHG test were also carried out. The EPR spectra were
      recorded for gamma-irradiated single crystal of ANPLT. The angular variation
      studies of the spectra were carried out and the principal values of g- and A
      tensors were determined. The site symmetry of the radical formed is axial.

PMID- 16950649
TI  - Humidity-dependent dynamic infrared linear dichroism study of a poly(ester
      urethane).
AB  - Fourier transform infrared techniques, infrared difference spectroscopy and
      dynamic infrared linear dichroism (DIRLD), have been utilized to explore the
      effects of humidity and water absorption on a poly(ester urethane). An
      environmental infrared microbalance cell was used to measure the infrared spectra
      as a function of humidity and accompanying weight change for the absorption
      desorption processes. The infrared difference data indicate that exposure to
      humidity affects the hydrogen-bonding interactions in the polymer. Dynamic
      infrared linear dichroism studies in tensile deformation mode as a function of
      humidity demonstrate how changes in water content affect the orientational
      response of functional groups. Complex behavior as a function of humidity for
      functional groups involved in hydrogen bonding indicates that water absorbed by
      the polymer affects the micro-environments near these functional groups.

PMID- 16950650
TI  - User-centered design techniques for a computerised antibiotic decision support
      system in an intensive care unit.
AB  - OBJECTIVE: To explore the use of user-centered design techniques for developing
      the requirements for an antibiotic decision support system (DSS) in an intensive
      care unit (ICU). DESIGN AND METHODOLOGY: The setting was a 21-bed mixed
      medical/surgical adult ICU. This was an observational study with unstructured
      interviews and participatory design process. Models were constructed to
      demonstrate cultural, workflow, sequence/trigger events and other artefacts used
      to support antibiotic prescribing in the ICU. Using participatory design, a paper
      prototype was developed and case studies were used to simulate antibiotic
      prescribing for bacterial isolates. This information was used to design and pilot
      the decision support tool. RESULTS: The key users were identified as residents,
      registrars and the unit pharmacist. They identified the major requirements:
      ability to collate and print microbiology results, and to provide education and
      antibiotic advice for isolates. The final product was a real time microbiology
      browser and decision support tool for antibiotic prescribing (ADVISE). Uptake of
      the system was rapid with over 6000 encounters in the first 6 months. An audit of
      antibiotic use performed on all consecutive patients 6 months before and after
      introducing the DSS demonstrated a reduction in total and broad-spectrum
      antibiotics. CONCLUSION: Contextual design methodology in conjunction with
      participatory design was an effective method to design this antibiotic decision
      support tool. The process facilitated physician and pharmacist ownership of the
      system that resulted in immediate uptake and ongoing use.

PMID- 16950651
TI  - First phase viral kinetic parameters and prediction of response to interferon
      alpha-2b/ribavirin combination therapy in patients with chronic hepatitis C.
AB  - The aim of the present study was to assess parameters in early phase HCV dynamics
      for predicting the outcome of interferon (IFN)/ribavirin combination therapy in
      patients with chronic hepatitis C (CH-C). Sixty-five CH-C patients who received
      IFN alpha-2b/ribavirin combination therapy were enrolled. The serum levels of HCV
      RNA 0h and 3 months after commencing therapy were serially quantified. HCV
      kinetic parameters such as quantity, ratio of decline, and half-life were
      analyzed. In genotype 1 patients, both the quantity and the ratio of decline of
      HCV RNA 24h after the start of therapy were useful predictors of a poor response.
      No patients who had serum HCV RNA above 200KIU/ml 24h after the start of therapy
      achieved a sustained viral response (SVR). In genotype 2 patients, conversely,
      these two parameters were predictors of a sustained viral response. The efficacy
      of these parameters in predicting the outcome of therapy was comparable to that
      of the disappearance of HCV RNA from sera at 4 weeks. These results demonstrate
      that parameters of HCV kinetics 24h after the start of therapy are useful for the
      early prediction of outcome in response to IFN alpha-2b/ribavirin combination
      therapy.

PMID- 16950652
TI  - DnaJA4 is a SREBP-regulated chaperone involved in the cholesterol biosynthesis
      pathway.
AB  - Using subtractive hybridization technique in 3T3-L1 adipocytes overexpressing
      constitutively active SREBP2, we have identified a DnaJ/Hsp40 chaperone, DnaJA4,
      as a new SREBP-responsive gene. SREBP2 regulation was demonstrated by changes in
      DnaJA4 mRNA under conditions of altered sterol status that were strictly parallel
      to that of well-characterized SREBP targets (LDL receptor and HMG-CoA reductase).
      The role of SREBP2 was further established using adenoviral overexpression of a
      dominant negative SREBP2, which abolished cholesterol-regulated changes in DnaJA4
      expression. To determine the functional significance of this regulation, DnaJA4
      was overexpressed in COS cells, which induced a specific increase in the
      synthesis of cholesterol from acetate. We also observed that DnaJA4
      overexpression increased the activity and the protein content of HMG-CoA
      reductase, the rate limiting enzyme in this pathway. At the molecular level,
      DnaJA4 overexpression did not alter HMG-CoA reductase stability or mRNA levels,
      suggesting a co-translational effect of the chaperone. In the DnaJ/Hsp40 family,
      DnaJA4 uniquely exhibited SREBP-regulated expression, and also responded to heat
      shock. Through its responsiveness to SREBP, and its stimulatory effect on
      cholesterol synthesis, the DnaJA4 chaperone can be viewed as a new player in
      cholesterol synthesis. These data suggest a link between molecular chaperones,
      heat stress and cholesterol synthesis.

PMID- 16950653
TI  - Fatty acid synthesis and elongation in yeast.
AB  - Fatty acids are essential compounds in the cell. Since the yeast Saccharomyces
      cerevisiae does not feed typically on fatty acids, cellular function and growth
      relies on endogenous synthesis. Since all cellular organelles are involved in--or
      dependent on--fatty acid synthesis, multiple levels of control may exist to
      ensure proper fatty acid composition and homeostasis. In this review, we
      summarize what is currently known about enzymes involved in cellular fatty acid
      synthesis and elongation, and discuss potential links between fatty acid
      metabolism, physiology and cellular regulation.

PMID- 16950654
TI  - Comparison of two email-delivered, pedometer-based interventions to promote
      walking among insufficiently active women.
AB  - Research on the effect of email-delivered, pedometer-based interventions on
      walking behavior and transtheoretical model (TTM) constructs is lacking.
      Therefore, the purpose of this study was to compare the effectiveness of two
      email-delivered, pedometer-based interventions designed to increase walking and
      TTM construct scores among insufficiently active women. Participants were
      randomly assigned to one of two 6-week intervention groups. Both groups wore
      pedometers, submitted step logs, and received weekly email reminders. One group
      also received in the emails suggested strategies based on TTM for increasing
      physical activity. Of the 74 women who began the study, 56 (age=41.5+/-7.6 years;
      body mass index=31.2+/-6.6kg/m(2); 86% Caucasian) completed the International
      Physical Activity Questionnaire and TTM questionnaires at baseline and post
      intervention. Participants in both groups combined increased weekly time spent
      walking (p=0.002) and their scores on TTM cognitive processes, behavioral
      processes, pros, and cons changed (p< or =0.001) from baseline to post
      intervention. The changes in walking and TTM scores did not differ between groups
      (p>0.05). The results of this study indicate that email-delivered, pedometer
      based interventions may impact walking and most TTM scores among insufficiently
      active women. Although preliminary, the findings provide additional evidence that
      this low-cost method of intervening may be an effective approach to combat
      physical inactivity in women.

PMID- 16950655
TI  - Complete regression of established subcutaneous B16 murine melanoma tumors after
      delivery of an HIV-1 Vpr-expressing plasmid by in vivo electroporation.
AB  - Novel therapies and delivery methods directed against malignancies such as
      melanoma, and particularly metastatic melanoma, are needed. The HIV-1 accessory
      protein Vpr (viral protein R) has previously been demonstrated to induce G2 cell
      cycle arrest as well as in vitro growth inhibition/killing of a number of tumor
      cells by apoptosis. In vivo electroporation has been utilized as an effective
      delivery method for pharmacologic agents and DNA plasmids that express
      "therapeutic" proteins and has been targeted to various tissues, including
      malignant tumors. For the study reported here, we hypothesized that intratumoral
      delivery of a Vpr expression plasmid through in vivo electroporation would induce
      apoptosis and growth attenuation or regression of melanoma tumors. Established
      subcutaneous B16.F10 melanoma tumors were injected intratumorally with a Vpr
      expressing (either 25 or 100 microg) plasmid, followed by electroporation, on day
      0 (i.e., when tumors had attained an appropriate size) and day 4. Treatment with
      25 or 100 microg of the Vpr-expressing plasmid resulted in complete tumor
      regression with long-term survival in 14.3 and 7.1% of the mice, respectively. In
      addition, electroporative delivery of the Vpr-expressing plasmid was shown to
      induce apoptosis in tumors after intratumoral injection. This is the first report
      demonstrating the ability of Vpr, when delivered as a DNA expression plasmid with
      in vivo electroporation, to attenuate melanoma lesion growth and induce complete
      tumor regression coupled with long-term survival of mice in a highly aggressive
      and metastatic solid tumor model.

PMID- 16950656
TI  - Febrile convulsions in developing rats induce a hyperanxious phenotype later in
      life.
AB  - Exposure of rodent pups to hyperthermia constitutes one of the best known models
      of febrile seizures. Studies designed to evaluate the behavioral impact of heat
      induced convulsions (HCs) have focused mainly on hippocampus-dependent tasks and
      produced rather conflicting results. In this study, we assessed, in detail,
      developmental milestones, emotional behavior, and cognitive performance in
      animals submitted to HCs on Postnatal Day 10. There was no alteration in the
      acquisition of neurological reflexes, but there was an anticipation of eye
      opening in animals exposed to hyperthermia. As adults, the locomotor and
      exploratory behavior of these rats was unaffected. Interestingly, animals exposed
      to hyperthermia displayed signs of increased anxiety in the elevated-plus maze,
      although these signs were not associated with increased susceptibility to
      depression-like behavior. Additionally, we failed to observe impairments in
      spatial and working memory tasks. In conclusion, HCs at a particular period of
      neurodevelopment determine a hyperanxious phenotype later in life.

PMID- 16950657
TI  - Musculoskeletal pain in primary health care: subgroups based on pain intensity,
      disability, self-efficacy, and fear-avoidance variables.
AB  - The purpose of this study was to identify and describe subgroup profiles based on
      self-reported pain intensity, disability, self-efficacy, fear of
      movement/(re)injury, and catastrophizing in patients with musculoskeletal pain.
      Two primary health care samples (n = 215 and n = 161) were used. Self-report
      questionnaires were completed at the start of physical therapy treatment. Cluster
      analysis was used to generate subgroups. Three subgroups were identified in
      sample 1 and replicated in sample 2. These were labeled "High self-efficacy-Low
      fear-avoidance," "Low self-efficacy-Low fear-avoidance," and "Low self-efficacy
      High fear-avoidance." The subgroups differed significantly in work-status in both
      samples (P < .001), but not in age, gender, or duration of pain. The results show
      the presence of subgroups based on pain intensity, disability, self-efficacy,
      fear of movement/(re)injury, and catastrophizing. The profile patterns suggest
      that different management strategies may be relevant in each subgroup.
      PERSPECTIVE: This article presents subgroups of patients with musculoskeletal
      pain with different profiles in pain intensity, disability, and psychosocial
      variables possible to modify by physical therapy management. The results could
      potentially aid clinicians in tailoring assessment and treatment approaches to
      each subgroup.

PMID- 16950658
TI  - Motion and space sickness: intestinal and autonomic correlates.
AB  - The purpose of this paper is to provide an overview of autonomic nervous system
      and gastrointestinal changes that occur during motion sickness. It is important
      to consider that motion sickness is a syndrome that can vary between individuals
      and within individuals and between and within motion sickness-inducing stimuli.
      Vomiting should be considered a discrete event of the motion sickness syndrome.
      Given so much variability in motion sickness symptoms, it should be expected that
      the physiological response to motion sickness will vary as well. This appears to
      be the case with the autonomic nervous system and gastrointestinal changes during
      motion sickness. Although much research remains to be done, it appears undeniable
      that the physiological expression of motion sickness is mediated by the autonomic
      nervous system, and when nausea is a predominant symptom, the stomach in general
      shuts down in a response characterized by decreased normal gastric myoelectrical
      activity and delayed gastric emptying.

PMID- 16950659
TI  - Acupuncture for nausea and vomiting: an update of clinical and experimental
      studies.
AB  - The objective of this overview is to summarize existing knowledge about the
      effects of acupuncture-point stimulation on nausea and vomiting. Systematic
      reviews on postoperative nausea and vomiting, chemotherapy-induced nausea and
      vomiting, and pregnancy-related nausea and vomiting exist. Several randomised
      trials, but no reviews, exist for motion sickness. For postoperative nausea and
      vomiting, results from 26 trials showed acupuncture-point stimulation was
      effective for both nausea and vomiting. For chemotherapy-induced nausea and
      vomiting, results of 11 trials differed according to modality with acupressure
      appearing effective for first-day nausea, electroacupuncture appearing effective
      for first-day vomiting, and noninvasive electrostimulation appearing no more
      effective than placebo for any outcome. For pregnancy-related nausea and
      vomiting, results were mixed. Experimental studies showed effects of P6
      stimulation on gastric myoelectrical activity, vagal modulation and cerebellar
      vestibular activities in functional magnetic resonance imaging. There is good
      clinical evidence from more than 40 randomised controlled trials that acupuncture
      has some effect in preventing or attenuating nausea and vomiting. A growing
      number of experimental studies suggest mechanisms of action.

PMID- 16950660
TI  - Functional effects and characteristics of cecum-projecting neurons in the dorsal
      motor nucleus of the vagus of rats.
AB  - Preganglionic neurons in the dorsal motor nucleus of the vagus (DMV) innervate
      most of the gastrointestinal tract; with the stomach and the cecum/proximal colon
      having a greater proportion of vagal input. Cecum-projecting neurons have been
      thought to be distinct from other preganglionic neurons due to their location
      within the DMV, but it is unknown whether these neurons innervate the cecum
      exclusively or what effect their activation has on cecal motor activity.
      Therefore, we investigated the extent of coinnervation of cecum and stomach by
      vagal neurons, their neurochemistry, and the effect of DMV stimulation on
      intracecal and intragastric volumes. Fluorescent retrograde tracers injected into
      the serosa of the cecum and stomach revealed that in the DMV 49+/-5% CTB-labeled
      cecum-projecting neurons also innervated the stomach. Immunocytochemical staining
      for nitric oxide (NO) synthase and tyrosine hydroxylase indicated that only 3+/
      1% and 4+/-1% of cecum-projecting neurons contained these markers, respectively.
      In anesthetized rats gastric and cecal volumes were measured by prototypic
      miniaturized dual barostats that were developed for use in rodents.
      Microinjection of l-glutamate into the DMV increased gastric contractile activity
      and tone, and reduced on-going cecum contractile activity (2.6+/-0.7
      contractions/2 min after injection versus 8.2+/-0.4 contractions/2 min before
      injection, N = 5). The barostat was able to detect decreases (-0.88+/-0.13 ml)
      and increases (0.25+/-0.05 ml) in cecum volume in response to carbachol and
      sodium nitroprusside, respectively. In summary, cecum-projecting neurons are not
      an entirely exclusive population within the DMV because a percentage of these
      also innervate the stomach. Central vagal stimulation can modulate both gastric
      and cecum contractile activity. Together, these data support a role of the vagus
      in neural reflexes involving gastric and large bowel motor function, such as the
      immediate phase of the gastrocolonic reflex.

PMID- 16950661
TI  - Central control of atrio-ventricular conduction and left ventricular
      contractility in the cat heart: Synaptic interactions of vagal preganglionic
      neurons in the nucleus ambiguus with neuropeptide Y-immunoreactive nerve
      terminals.
AB  - In the cat, vagal postganglionic controls of heart rate, atrio-ventricular (AV)
      conduction and left ventricular contractility are mediated by three separate
      intrinsic cardiac ganglia, the sinoatrial (SA), AV and cranioventricular (CV)
      ganglia, respectively. The vagal preganglionic neurons (VPNs) that project to
      these ganglia are located in the ventrolateral nucleus ambiguus (NA-VL). We have
      previously shown that the VPNs projecting to the SA, AV and CV ganglia are
      distinct from one another. We have also demonstrated that neuropeptide Y
      immunoreactive (NPY-IR) axon terminals synapse upon VPNs projecting to the SA
      ganglion. In the present study, we test the hypothesis that those VPNs projecting
      to the AV ganglion (negative dromotropic VPNs) and those projecting to the CV
      ganglion (negative inotropic VPNs) are innervated by NPY-IR terminals in NA-VL. A
      retrograde tracer was injected into the AV or CV ganglion of the cat, and the
      brains subsequently processed for visualization of tracer and the
      immunocytochemical visualization of NPY by dual labeling electron-microscopic
      methods. We observed that 11+/-5% of all axodendritic synapses and 8+/-6% of all
      axosomatic synapses upon negative inotropic VPNs were NPY-IR. Furthermore, 19+/
      14% of all axodendritic synapses upon negative dromotropic VPNs were NPY-IR. A
      few NPY-IR axosomatic synapses upon negative dromotropic neurons were also
      observed. NPY-IR terminals in NA-VL occasionally formed axosomatic synapses with
      NPY-IR neurons and axoaxonic synapses with unlabeled terminals. These results
      suggest that central NPY afferents to the NA-VL modulate the vagal preganglionic
      control of AV conduction and left ventricular contractility.

PMID- 16950662
TI  - Conditioned gaping in rats: a selective measure of nausea.
AB  - When intraorally infused with a flavored solution previously paired with an
      emetic drug, rats display a characteristic gaping reaction that reflects
      conditioned nausea in this species that is unable to vomit. The commonly used
      conditioned taste avoidance measure, is not a selective measure of nausea because
      nearly every drug tested (even rewarding drugs) is capable of producing a
      conditioned taste avoidance. In contrast, only emetic drugs produce conditioned
      gaping reactions in rats, and anti-emetic drugs interfere with the establishment
      and the expression of conditioned gaping reactions but do not interfere with
      conditioned taste avoidance. The conditioned gaping reaction can be used as a pre
      clinical tool to evaluate the side effects of nausea that might result from newly
      developed pharmaceutical agents.

PMID- 16950663
TI  - Expression of marker genes during early ear development in medaka.
AB  - Induction of the otic placode involves a number of regulatory interactions. Early
      studies revealed that the induction of this program is initiated by instructive
      signals from the mesendoderm as well as from the adjacent hindbrain. Further
      investigations on the molecular level identified in zebrafish Fgf3, Fgf8, Foxi1,
      Pax8, Dlx3b and Dlx4b genes as key players during the induction phase. Thereafter
      an increasing number of genes participates in the regulatory interactions finally
      resulting in a highly structured sensory organ. Based on data from zebrafish we
      selected medaka genes with presumptive functions during early ear development for
      an expression analysis. In addition we isolated Foxi1 and Dlx3b gene fragments
      from embryonic cDNA. Altogether we screened the spatio-temporal distribution of
      more than 20 representative marker genes for otic development in medaka embryos,
      with special emphasis on the early phases. Whereas the spatial distribution of
      these genes is largely conserved between medaka and zebrafish, our comparative
      analysis revealed several differences, in particular for the timing of
      expression.

PMID- 16950664
TI  - Electrochemical behaviors of native and thermally denatured fish DNA in the
      presence of cytosine derivatives and porphyrin by cyclic voltammetry using boron
      doped diamond electrode.
AB  - The electrochemical behaviors of native and thermally denatured fish DNA was
      investigated using boron-doped diamond (BDD) film electrode by cyclic
      voltammetry. The BDD electrode afforded us to measure weak current less than muA
      for the DNA solution in 100 microl. The mixture of acetic acid and sodium acetate
      solution (0.2 M) was used as a supporting electrolyte. Two oxidation peaks were
      observed at about +1.1 V and +1.3 V at pH 4.6 for thermally denatured fish DNA.
      This is due to the oxidation of guanine and adenine in the denatured fish DNA,
      respectively. In contrast, the native fish DNA showed ill-defined peaks at +1.1
      V. Furthermore, the electrochemical behaviors of thermally denatured fish DNA
      were studied in the presence of cytosine, cytidine, cytidine-5-monophosphate,
      tetrakis(1-methypyridinium-4-yl)porphyrin (H(2)(TMPyP)(4+)) and
      Ru(II)(TMPyP)(4+). The oxidation peak intensity at +1.1 V gradually decreased
      with the increase of the concentrations of the above compounds. Based on the
      above studies, electrochemical behaviors of the thermally denatured fish DNA at
      BDD electrode is discussed.

PMID- 16950665
TI  - The adversities of aging.
AB  - The aging process is evolutionarily conserved and subject to quantitative
      modification by both genetic and environmental factors. Fundamental mechanisms of
      aging result in progressive deficits in the function of cells and organs, often
      leading to diseases that ultimately kill the organism such as cancers,
      cardiovascular disease and neurodegenerative disorders. Oxidative stress and
      damage to all of the major classes of molecules in cells are involved in aging
      and age-related diseases. The widely pursued approach of targeting disease
      specific processes to develop therapeutic interventions has not had a major
      impact on healthspan. A more productive approach would be to target the
      fundamental mechanisms of aging throughout adult life so as to extend healthspan.
      Caloric restriction and regular exercise are two such approaches.

PMID- 16950666
TI  - Review of methodology for the determination of macrocyclic lactone residues in
      biological matrices.
AB  - The macrocyclic lactones (MLs) are probably the anti-parasitic agents most widely
      used in the treatment of food producing animals, poultry, aquaculture and crops.
      Ivermectin was the first macrocyclic lactone product to be licensed for use about
      20 years ago. A number of alternative products such abamectin, doramectin,
      emamectin, eprinomectin, moxidectin, milbemycin and selamectin, have been
      marketed since. Because of the increase in the number of ML drugs, there has been
      a steady increase in the number of published analytical methods for determination
      of their residues. In this paper, the structure and properties of the different
      ML drugs available on the market are described. The occurrence and persistence of
      ML residues in food is discussed in relation to marker residues and current
      maximum residue limits (MRLs) as defined in the European Union (EU).
      Methodologies for determination of ML residues in biological matrices are
      described in terms of extraction and clean-up methods used for different
      matrices. Detection systems for determination of ML residues are discussed with a
      particular emphasis placed on new developments in screening technologies and
      liquid chromatography with fluorescence or mass spectrometry.

PMID- 16950667
TI  - Analysis of nitrite and nitrate in biological fluids by assays based on the
      Griess reaction: appraisal of the Griess reaction in the L-arginine/nitric oxide
      area of research.
AB  - In the Griess reaction, first reported by Johann Peter Griess in 1879 as a method
      of analysis of nitrite (NO(2)(-)), nitrite reacts under acidic conditions with
      sulfanilic acid (HO(3)SC(6)H(4)NH(2)) to form a diazonium cation (HO(3)SC(6)H(4)
      N[triple bond]N(+)) which subsequently couples to the aromatic amine 1
      naphthylamine (C(10)H(7)NH(2)) to produce a red-violet coloured (lambda(max)
      approximately 540 nm), water-soluble azo dye (HO(3)SC(6)H(4)-NN-C(10)H(6)NH(2)).
      The identification of nitrite in saliva has been the first analytical application
      of this diazotization reaction in 1879. For a century, the Griess reaction has
      been exclusively used to identify analytically bacterial infection in the
      urogenital tract, i.e. to identify nitrite produced by bacterial reduction of
      nitrate (NO(3)(-)), the major nitrogen oxide anion in human urine. Since the
      discovery of the l-arginine/nitric oxide (l-Arg/NO) pathway in 1987, however, the
      Griess reaction is the most frequently used analytical approach to quantitate the
      major metabolites of NO, i.e. nitrite and nitrate, in a variety of biological
      fluids, notably blood and urine. The Griess reaction is specific for nitrite.
      Analysis of nitrate by this reaction requires chemical or enzymatic reduction of
      nitrate to nitrite prior to the diazotization reaction. The simplicity of the
      Griess reaction and its easy and inexpensive analytical feasibility has attracted
      the attention of scientists from wide a spectrum of disciplines dedicated to the
      complex and challenging L-Arg/NO pathway. Today, we know dozens of assays based
      on the Griess reaction. In principle, every laboratory in this area uses its own
      Griess assay. The simplest Griess assay is performed in batch commonly as
      originally reported by Griess. Because of the recognition of numerous
      interferences in the analysis of nitrite and nitrate in biological fluids and of
      the desire to analyze these anions simultaneously, the Griess reaction has been
      repeatedly modified and automated. In recent years, the Griess reaction has been
      coupled to HPLC, i.e. is used for post-column derivatization of
      chromatographically separated nitrite and nitrate. Such a HPLC-Griess system is
      even commercially available. The present article gives an overview of the
      currently available assays of nitrite and nitrate in biological fluids based on
      the Griess reaction. Special emphasis is given to human plasma and urine, to
      quantitative aspects, as well as to particular analytical and pre-analytical
      factors and problems that may be associated with and affect the quantitative
      analysis of nitrite and nitrate in these matrices by assays based on the Griess
      reaction. The significance of the Griess reaction in the L-Arg/NO pathway is
      appraised.

PMID- 16950668
TI  - Experimental and computational approach for evaluating the mechanical
      characteristics of dental composite resins with various filler sizes.
AB  - This study aimed to investigate the influence of particle size of fillers on
      flexural properties of dental composite resins by laboratory testing with
      computational analysis validation. Four kinds of silica fillers with mean
      particle sizes of 3.3, 4.3, 7.9, and 15.5 microm were used. Filler content was
      kept constant at 70 mass% (or 53.8 vol.%). The three-point bending test was
      performed with a constant loading speed of 1.0mm/min, and a span length of 20mm
      using an Instron machine, in order to measure flexural strength and modulus of
      composite resins with various particle sizes. Test specimens were 2-mm wide, 2-mm
      thick, and 25-mm long rectangular bars. Furthermore, a numerical simulation using
      three-dimensional finite element (FE) analysis was performed to investigate
      stress distribution in composite resins under loading. As a result, flexural
      strength decreased with increasing particle size of the filler of the composite
      resins (p<0.05). On the other hand, there was no significant difference in
      Young's modulus among composite resins with various filler sizes (p>0.05).
      Moreover, FE analysis indicated that stress concentration increased with
      increasing particle size in agreement with experimental results of flexural
      strength. In conclusion, within the limitations of this investigation, we
      confirmed that flexural strength of composite resins decreased with increasing
      filler particle size. In addition, FE analysis was effective for evaluating
      stress distributions of dental composite resins with various filler sizes.

PMID- 16950669
TI  - Vitamin D status and bone mass in UK South Asian women.
AB  - INTRODUCTION: Low vitamin D status is prevalent among South Asians living in the
      UK. The relationship, however, between serum 25-hydroxyvitamin D level (25OHD),
      serum parathyroid level (PTH) and bone mass in this group of women is unknown.
      The aim of this study was to determine the association between serum PTH, 25OHD
      and bone mass in a population based sample of young UK South Asian women.
      MATERIALS AND METHODS: Names of South Asian women aged 18 to 36 years of
      Pakistani origin living in the Greater Manchester area were identified from
      primary care registers using validated computer software. Subjects were invited
      to attend for (i) a blood test for assessment of serum calcium (Ca), albumin, PTH
      and 25OHD and (ii) for bone mineral density (BMD) scanning using the following:
      areal BMD at the hip (femoral neck, total hip) and lumbar spine using dual X-ray
      absorptiometry (Hologic QDR 4500), and volumetric BMD at the distal radius using
      peripheral quantitative computed tomography (Norland Stratec XCT 2000). Linear
      regression was used to determine the association between serum 25OHD, PTH and BMD
      at the different sites with adjustments made for age. RESULTS: In all, 78 women
      (mean age 29.2 years) were included in the analysis. Mean serum Ca level was 2.42
      mmol/l, 25OHD, 7.9 ng/ml and PTH, 52.8 pg/ml. The majority of women (94%) had
      serum 25OHD levels <or=15 ng/ml, while 20 (26%) had evidence of marked deficiency
      (<or=5 ng/ml). Mean serum PTH level was similar in subjects with a serum 25OHD of
      10.1-15 ng/ml and >15 ng/ml, though rose progressively in subjects with levels
      below 10 ng/ml. Serum 25OHD was positively associated with BMD at the hip and
      spine while PTH was negatively associated with BMD at the hip and spine. When
      categorized by serum 25OHD level there was an increase in BMD at the total hip
      and distal radial site at least up to levels of 15 ng/ml. CONCLUSIONS: Despite
      widespread recognition, hypovitaminosis D is still prevalent among young UK South
      Asian women. In these women a decrease in serum 25OHD level <or=15 ng/ml is
      associated with a progressive reduction in bone mass at the hip and wrist.

PMID- 16950670
TI  - Activated c-Fms recruits Vav and Rac during CSF-1-induced cytoskeletal remodeling
      and spreading in osteoclasts.
AB  - Colony-stimulating factor-1 (CSF-1) induces osteoclast spreading that requires
      activation of c-Src and phosphatidyl inositol 3-kinase (PI3-K), both of which are
      recruited to activated c-Fms, the CSF-1 receptor. The present report provides
      evidence that the hemopoietic guanine nucleotide exchange factor (GEF), Vav, and
      its target GTPase, Rac, lie downstream from this initial signaling complex. CSF-1
      treatment of osteoclast-like cells induced translocation of Vav to the plasma
      membrane, an increase in its phosphotyrosine content, and a concomitant decline
      in the amount of phosphoinositol 4,5-bisphosphate bound to Vav, changes known to
      induce Vav's GEF activity. CSF-1 induced the association of Vav and Rac and
      increased Rac's GTPase activity. CSF-1 also induced rapid translocation of Rac to
      the periphery of spreading neonatal rat osteoclasts where it co-localized
      primarily with Vav3 and to a lesser extent with Vav1. Wortmannin, an inhibitor of
      PI3-K, blocked CSF-1-induced Rac translocation and prevented CSF-1-induced
      spreading and actin reorganization in osteoclasts. CSF-1-induced osteoclast
      spreading was not significantly reduced in osteoclasts isolated from Vav1 knock
      out mice and Vav1 knock-out mice had normal bone density. Microinjection of
      constitutively active Rac, but not constitutively active Cdc42 or RhoA, induced
      lamellipodia formation and osteoclast spreading, mimicking the effects of CSF-1.
      Dominant-negative Rac blocked CSF-1-induced osteoclast spreading, whereas neither
      dominant-negative Cdc42 nor C3, an inhibitor of RhoA, affected the response to
      CSF-1. These data demonstrate that Vav and Rac lie downstream from activated PI3
      K in CSF-1-treated osteoclasts and that Rac is required for CSF-1-induced
      cytoskeletal remodeling in these cells.

PMID- 16950671
TI  - Immature platelet fraction as a predictor of platelet recovery following
      hematopoietic progenitor cell transplantation.
AB  - The immature platelet fraction (IPF) as determined by the Sysmex XE-2100 is a
      rapid automated measure of the least mature component of the platelet population
      and is thought to correlate with thrombopoietic activity of the marrow. We
      investigated the ability of IPF to predict platelet recovery following
      hematopoietic progenitor cell (HPC) transplantation. IPF was compared to standard
      parameters of hematopoietic recovery, including the immature reticulocyte
      fraction (IRF), an early predictor of recovery. Fifty patients undergoing
      peripheral blood HPC transplantation (38 autologous and 12 allogeneic) were
      followed daily for 11 to 28 days after transplantation with measurement of IPF,
      IRF, absolute neutrophil counts (ANC) and platelet counts. Mean days to recovery
      for IPF was 3.1 days less than for platelet count (P <.0001), 3.8 days less than
      for ANC (P <.0001), and 0.6 days less than for IRF (P = .0477). IPF recovered at
      least 1 day prior to platelet count in 79% (38 of 48) of patients, and was
      followed by platelet count recovery within 1 to 12 days (mean, 4.1 days). When
      autologous and allogeneic patient groups were analyzed separately, IPF recovered
      significantly earlier than platelet count and ANC in both groups (P <.0001).
      Thrombopoietin (TPO) levels in 5 patients receiving transplants correlated with
      IPF; however, this appeared to be secondary to an inverse correlation of both TPO
      and IPF with platelet count. IPF is comparable to IRF as one of the earliest
      predictors of hematopoietic recovery following peripheral blood HPC
      transplantation. IPF could potentially be useful as a predictor of platelet
      recovery in other bone marrow failure syndromes.

PMID- 16950672
TI  - Prothrombin gene 20209 C >T along with the first description of a homozygous
      polymorphism at the 3' downstream region +4 C >T in the Turkish population.
AB  - Mutation screening studies related with thrombosis revealed that prothrombin
      20210A allele of the prothrombin gene leads to an increase in plasma prothrombin
      levels. The G20210A mutation screening has become a routine analysis in patients
      with thrombosis. For the detection of the mutation, several molecular techniques
      have been defined. Real-time polymerase chain reaction is an easy and feasible
      way to monitor this mutation according to the melting point analysis. Here we
      report a different pattern in the LightCycler melting point analysis of 2
      patients with thrombosis. DNA sequencing of the prothrombin gene showed that
      these patients with an atypical melting point profile carry a 20209 C >T mutation
      along with a novel homozygous polymorphism at the 3' downstream region, +4 C >T.

PMID- 16950673
TI  - Differences in mortality on the basis of complete blood count in an unselected
      population at the emergency department.
AB  - The objective of this descriptive study was to relate hematological parameters of
      patients visiting the emergency department (ED) to mortality. The study included
      1698 adult patients visiting the ED for any reason who underwent blood gas
      analysis. The results of hemoglobin concentration, leukocyte count, and platelet
      count were related to mortality within 7 days after admittance to the hospital.
      When comparing survivors and nonsurvivors, age (mean, 54 versus 63 years, p <
      .0001) and leukocyte count (median, 10.8 versus 13.9 x 10 (9)/L, p < .0001)
      showed significant differences. Further analysis was performed by dividing the
      group of patients according to the reference range. This showed higher mortality
      in the groups of patients with leukocyte counts outside the reference range (4.0
      10.0 x 10 (9)/L, p < .01) and in the group of patients with platelet counts below
      the reference range (150-450 x 10 (9)/L, p < .0001). High mortality is also seen
      in the group of women with hemoglobin concentrations outside the reference range
      (12.1-15.7 g/dL, p < .01), for men no difference was observed. In conclusion, our
      study shows clinically relevant differences in mortality in hematological
      parameters in an unselected population at the ED, irrespective of underlying
      pathology.

PMID- 16950674
TI  - Common alpha-thalassemia deletions in transfusion-dependent thalassemia patients
      in the Southeast Asia region of Myanmar.
AB  - Screening of 3 common alpha-thalassemia (thal) deletions (-alpha3.7, -alpha4.2
      and --SEA) in Southeast Asia was done by polymerase chain reaction in 170
      unrelated Myanmar thal patients receiving transfusions. Thal deletions were
      detected in 27 patients (15.9%) as: (1) alpha-thal-2 (-alpha3.7/alphaalpha) in 12
      heterozygous or hemoglobin (Hb) E-beta-thal cases; (2) alpha-thal-1 in 7 patients
      (2-alpha3.7/-alpha3.7 and 5 --SEA/alphaalpha); and (3) Hb H (-alpha3.7/--SEA) in
      8 patients. The latter 15 alpha-thal-1 and Hb H patients had no beta-thal
      mutations and represented 8.8% of the overall patients seeking transfusion for
      refractory anemia in Myanmar. This is the first description of alpha-thal in
      Myanmar from the molecular aspect, and its clinical and racial heterogeneity are
      described and discussed.

PMID- 16950675
TI  - Examination of stability of bone marrow blood RNA in the PAXgene tube.
AB  - The PAXgene RNA blood collection tube is used for RNA of peripheral blood (PB)
      and the stability of PB RNA in this tube has already been reported. However, the
      stability of bone marrow blood (BM) RNA in the PAXgene tube is unknown. Thus, we
      examined the stability of BM RNA in the PAXgene tubes. BM from leukemia patients
      was collected into PAXgene and EDTA tubes and stored at 4 degrees C for 5 days.
      RNA isolated from both tubes was analyzed by a quantitative reverse-transcription
      polymerase chain reaction (RT-PCR) analysis. Porphobilinogen deaminase (PBGD)
      mRNA of BM (as high-expression mRNA) and Wilms tumor suppressor (WT1) mRNA of BM
      (as low-expression mRNA) and very low copies of major BCR-ABL mRNA (as minimal
      residual disease of leukemia) of leukemia of BM were quantified by a LightCycler
      system. RNA yield from the PAXgene tubes and the intensity of 28S rRNA bands on
      RNA electrophoresis showed a degradation trend. However, the intensity of 18S
      rRNA bands from the PAXgene tubes remained. The expression of PBGD and WT1 of BM
      in the PAXgene tubes did not decrease for 5 days. The very low copies of major
      BCR-ABL mRNA in the PAXgene tubes were detectable on day 5 but those in the EDTA
      tubes were not detectable. Therefore, the PAXgene tube can be used for BM samples
      in a quantitative RT-PCR of the fusion gene transcripts of leukemia.

PMID- 16950676
TI  - Lactate dehydrogenase-linked immunoglobulin Akappa in a patient with nonimmune
      chronic idiopathic neutropenia.
AB  - A 39-year-old patient with cervical cancer, stage Ia, was successfully treated by
      total hysterectomy. Then, after sustained neutropenia for more than 4 years and
      coincident with its exacerbation, the serum lactate dehydrogenase (LD) level
      started to elevate and reached a plateau. A test for antineutrophil antibody was
      negative and LD-3-linked IgAkappa, which may be responsible for high LD activity,
      was confirmed. The absolute number of blood NK cells was reduced, and a diagnosis
      of nonimmune chronic idiopathic neutropenia of adult was made. The successive
      occurrence of these 3 disorders may be based on interrelated immunological
      abnormalities.

PMID- 16950677
TI  - Laboratory comparison of the VisuLize IX antigen assay with the Asserachrome IX
      antigen assay.
AB  - Factor IX antigen levels are used primarily to assess factor IX levels in
      patients with liver insufficiency or who are receiving oral vitamin K antagonist
      therapy. We evaluated the test performance of a new factor IX antigen enzyme
      linked immunoassay kit and compared it to our currently used enzyme-linked
      immunoassay method. Samples from normal donors and patients with known hemophilia
      B of varying severity were tested by using a predicate factor IX antigen method
      (Asserachachrome IX:Ag) and a new factor IX antigen method (VisuLize IX Antigen).
      The 2 methods were evaluated for performance, correlation, differences, and bias.
      Test samples included 46 normal donors, 14 commercial products, and 16, 18, and
      15 severe, moderate, and mildly deficient factor IX deficient plasmas,
      respectively. The 2 methods correlated well using regression analysis. However,
      there were significant differences using the paired t test with bias plots
      indicating higher absolute values for the VisuLize IX antigen method in the
      severe and moderate deficiency range, but not the normal range. Testing
      commercially prepared survey material, the Asserachrome method demonstrated a
      consistently lower result than expected. The VisuLize factor IX is a new method
      for determining antigenic levels in human plasma. This method has a much shorter
      incubation time and demonstrates good correlation with current factor IX
      antigenic methods.

PMID- 16950679
TI  - XIXth International Symposium on Technological Innovations in Laboratory
      Hematology. Amsterdam, The Netherlands. April 25-28, 2006. Poster Abstracts Part
      II.

PMID- 16950678
TI  - Use of red blood cells stored in saline suspension for immediate spin crossmatch.
AB  - The purpose of this study was to validate a procedure for using red blood cell
      suspensions stored for up to 10 days in an immediate spin crossmatch. Ten group A
      and 10 group B SAG-M donor unit segments were opened on day 0. The red cells were
      divided into 2 tubes and each diluted with saline to a 3% to 5% cell suspension.
      The cell suspensions were tested using a standard immediate spin technique
      against pooled group A, group B, and group O plasma each day for 10 days. One set
      of cells was stored refrigerated as a 3% to 5% cell suspension. Saline was
      removed from the parallel set of cells before storage. All 480 tests that were
      expected to be negative were negative. On 2 separate occasions 1+ or 2+ reactions
      that disappeared before the cell button was completely resuspended were noted.
      All 960 tests that were expected to be positive were positive. All but 4 results
      were graded as 3+ or 4+. Four 2+ reactions occurred with 2 units that were typed
      as A1 negative. Our results indicate that cells stored refrigerated in normal
      saline as a 3% to 5% cell suspension may be used for immediate spin crossmatch
      for up to 10 days.

PMID- 16950682
TI  - Does the more vivid imagery of high hypnotizables depend on greater cognitive
      effort? A test of dissociation and social-cognitive theories of hypnosis.
AB  - In an investigation of the role of cognitive effort in hypnotic responding, high
      and low hypnotizable participants produced emotionally neutral imagery in
      response to effortful versus effortless hypnotic suggestions. Heart-rate increase
      served as an objective index of cognitive effort, and subjective ratings of
      imagery vividness, absorption, effort, and control were collected. Compared to
      lows, high hypnotizable participants experienced their imagery as more vivid and
      absorbing, yet their heart rates indicated no higher level of cognitive effort
      than lows. Compared to effortless wording, effortful wording of suggestions
      increased cognitive effort in lows, as indexed by heart-rate increase, but had no
      effect on the effort expended by highs. Ratings of subjective control were
      strongly correlated with subjective effort for lows but unrelated for highs.
      These results support the dissociated-control theory of hypnosis rather than the
      dissociated-experience or social-cognitive theories.

PMID- 16950683
TI  - Types of suggestibility: Relationships among compliance, indirect, and direct
      suggestibility.
AB  - It is commonly believed that direct suggestibility, referring to overt influence,
      and indirect suggestibility, in which the intention to influence is hidden,
      correlate poorly. This study demonstrates that they are substantially related,
      provided that they tap similar areas of influence. Test results from 103
      students, 55 women and 48 men, were entered into regression analyses. Indirect
      suggestibility, as measured by the Sensory Suggestibility Scale for Groups, and
      compliance, measured by the Gudjonsson Compliance Scale, were predictors of
      direct suggestibility, assessed with the Barber Suggestibility Scale. Spectral
      analyses showed that indirect suggestibility is more related to difficult tasks
      on the BSS, but compliance is more related to easy tasks on this scale.

PMID- 16950684
TI  - Hypnosis to manage anxiety and pain associated with colonoscopy for colorectal
      cancer screening: Case studies and possible benefits.
AB  - This study explored using hypnosis for pain and anxiety management in 6
      colonoscopy patients (5 men, 1 woman), who received a hypnotic induction and
      instruction in self-hypnosis on the day of their colonoscopy. Patients' levels of
      anxiety were obtained before and after the hypnotic induction using Visual
      Analogue Scales (VAS). Following colonoscopy, VASs were used to assess anxiety
      and pain during colonoscopy, perceived effectiveness of hypnosis, and patient
      satisfaction with medical care. Hypnotizability was assessed at a separate
      appointment. The authors also obtained data (time for procedure, number of
      vasovagal events, and recovery time) for 10 consecutive patients who received
      standard care. Results suggest that hypnosis appears to be a feasible method to
      manage anxiety and pain associated with colonoscopy, reduces the need for
      sedation, and may have other benefits such as reduced vasovagal events and
      recovery time.

PMID- 16950685
TI  - Satisfaction with, and the beneficial side effects of, hypnotic analgesia.
AB  - Case study research suggests that hypnosis treatment may provide benefits that
      are not necessarily the target of specific suggestions. To better understand
      satisfaction with and the beneficial "side effects" of hypnosis treatment,
      questions inquiring about treatment satisfaction and treatment benefits were
      administered to a group of 30 patients with chronic pain who had participated in
      a case series of hypnotic analgesia treatment. The results confirmed the authors'
      clinical experience and showed that most participants reported satisfaction with
      hypnosis treatment even when the targeted symptom (in this case, pain intensity)
      did not decrease substantially. Study participants also reported a variety of
      both symptom-related and nonsymptom-related benefits from hypnosis treatment,
      including decreased pain, increased perceived control over pain, increased sense
      of relaxation and well-being, and decreased perceived stress, although no single
      benefit was noted by a majority of participants.

PMID- 16950686
TI  - Examining sympathetic nerve activity with microneurography during hypnosis:
      untangling the effects of central command.
AB  - Using microelectrode recordings of postganglionic sympatheticaction potentials,
      the authors studied the effects of hypnotic suggestion on sympathetic outflow
      targeted to skin during static handgrip exercise. All subjects performed
      sustained handgrip at 33% maximal voluntary contraction (MVC) for 2 minutes
      during 3 consecutive trials. Two subjects randomly assigned to a hypnosis
      condition received suggestions that the 2nd trial was more difficult and the last
      trial was less difficult than the first trial. Two subjects randomly assigned to
      the control condition received no hypnosis or suggestions about task difficulty.
      In the nonhypnosis condition, skin sympathetic nerve activity (SNA) increased by
      6% from baseline during the 2nd trial and 13% from baseline during the 3rd trial.
      In the hypnosis condition, skin SNA increased by 25% during the 2nd trial
      (suggestion of increased difficulty) and returned to baseline during the 3rd
      condition (suggestion of decreased difficulty). Therefore, the impact of central
      command on skin SNA is suggested by these results.

PMID- 16950687
TI  - Neurophysiologic and long-term effects of clinical hypnosis in oral and
      maxillofacial treatment--a comparative interdisciplinary clinical study.
AB  - This prospective comparative clinical study evaluated the effectiveness of
      clinical hypnosis and its long-term effect in oral and maxillofacial treatment. A
      total of 45 highly anxious and nonanxious subjects were evaluated by subjective
      experience and objective parameters. Parameters were EEG, ECG, heart rate, blood
      pressure, blood oxygen saturation, respiration rate, salivary cortisol
      concentration, and body temperature. During and subsequent to the operative
      treatment, hypnosis led to a significant reduction of systolic blood pressure,
      and respiration rate and to significant changes in the EEG. The subjective values
      of the parameters evaluated existing anxiety mechanisms and patterns and possible
      strategies to control them, whereas the objective parameters proved the
      effectiveness of hypnosis and its long-term effect.

PMID- 16950688
TI  - Reassessment of hypnotic symptom removal by Freud and Bernheim.
AB  - As demonstrations of clinical efficacy, cases reported by Freud and Bernheim
      reveal an intrinsic advantage of hypnotic symptom removal over therapies
      requiring extended periods to achieve significant outcomes. They also lend
      support to Weitzenhoffer's survey of therapeutic results achieved during the
      classical (pre-1900) period.

PMID- 16950689
TI  - Enhancing thought suppression with hypnosis.
AB  - Much research indicates that attempts to suppress thoughts lead to increased
      accessibility of those thoughts, especially when additional cognitive load is
      present. On the premise that hypnosis may permit more effective management of
      cognitive load, it was hypothesized that hypnosis may enhance more effective
      thought suppression. The present research examined whether the obstacle of
      cognitive load could be bypassed using hypnosis to facilitate successful thought
      suppression. Thirty-nine high and 40 low hypnotizable participants were
      hypnotized and received either a suppression instruction or no instruction for a
      memory of an embarrassing experience and subsequently completed a sentence
      unscrambling task that indexed accessibility of embarrassing thoughts. Whereas
      lows instructed to suppress displayed a delayed increase in suppressed thoughts,
      highs did not. These findings support the proposition that hypnosis facilitates
      thought suppression.

PMID- 16950690
TI  - Musculoskeletal and emergency radiology.

PMID- 16950691
TI  - A word of caution from a local hospital.

PMID- 16950692
TI  - Multiple film reading in breast cancer screening.

PMID- 16950693
TI  - Regression of nodular liver lesions in Wilson's disease.
AB  - Long-term follow-up abdominal imaging studies have not been reported previously
      in patients with the hepatic form of Wilson's disease (WD). This paper reports
      the case of a 35-year-old woman with symptoms dating back several months and with
      multiple, nodular liver lesions. The lesions were hyperdense on non-enhanced
      computed tomography and hypointense on T2-weighted magnetic resonance (MR)
      images. A diagnosis of WD was established several weeks after her admission to
      hospital, and chelating treatment was commenced promptly. No abnormalities were
      found on follow-up MR examinations of the abdomen and brain 4.5 years later.
      These imaging features suggest that so long as WD is diagnosed in the initial
      stages, liver nodules can regress with time and complete healing can be achieved
      with continuous decoppering treatment.

PMID- 16950694
TI  - Effects of three different swallow maneuvers analyzed by videomanometry.
AB  - PURPOSE: To evaluate the manometric effects of three different swallow maneuvers
      on healthy volunteers. MATERIAL AND METHODS: Ten healthy volunteers with no
      history of swallowing complaints were evaluated with simultaneous
      videoradiography and pharyngeal manometry (videomanometry). Three different
      swallow maneuvers were evaluated (supraglottic swallow, super-supraglottic
      swallow, and Mendelsohn's maneuver) and seven manometric and two
      videoradiographic variables were analyzed. RESULTS: The supraglottic swallow
      showed a significantly weaker peak contraction of the upper esophageal sphincter
      (UES). The super-supraglottic swallow had a significantly higher UES relaxation
      pressure and the Mendelsohn maneuver a significantly higher UES peak contraction.
      With the Mendelsohn maneuver, there was also a significantly longer duration of
      the pharyngeal contraction and a significantly weaker UES peak contraction. Both
      the super-supraglottic and the Mendelsohn maneuver had a significantly longer
      bolus transit time. CONCLUSION: Our study did not show any significant difference
      in the relaxation duration of any of the swallowing maneuvers compared to a
      control swallow. With the Mendelsohn maneuver, we found that both the pharyngeal
      peak contraction and contraction duration were increased, which might result in
      an improved propulsion of bolus into the esophagus.

PMID- 16950695
TI  - Quantitative assessment of iron-oxide-enhanced magnetic resonance imaging of the
      liver: Vessel isointensity is a potential characteristic of liver hemangiomas on
      late T1-weighted images.
AB  - PURPOSE: To test whether a new quantitative measure, the tumor-to-vessel ratio,
      obtained from late post-iron-oxide-enhanced T1-weighted images allows for
      differentiating hemangiomas from liver metastases or all malignant liver lesions.
      MATERIAL AND METHODS: Twenty-six patients (mean 57, range 33-79 years) were
      prospectively studied at 1.5T magnetic resonance imaging (MRI) with a T1-weighted
      2D fast low-angle shot (FLASH) sequence (repetition time/echo time/flip angle;
      200 ms/4.8 ms/90 degrees ) and a T2-weighted turbo spin-echo sequence (4072 ms/99
      ms/180 degrees ). Imaging was carried out before and at intervals up to 18 min
      after IV injection of Ferucarbotran (Resovist, Schering, Germany). In 19
      patients, one representative malignant lesion was analysed. Eleven hemangiomas
      were evaluated in 7 patients. Two readers performed a consensus reading with a
      signal intensity measurement in a lesion, normal liver and hepatic veins, from
      which ratios were computed. RESULTS: On T1-weighted iron-oxide-enhanced MRI of 30
      lesions, tumor-to-vessel signal intensity ratios were distinct in hemangiomas
      (median 1.04, range 0.99-1.10) as opposed to either metastases (0.64, 0.33-0.77;
      P < 0.05) or all malignant lesions taken together (0.64, 0.33-0.98; P < 0.05),
      while the tumor-to-liver ratio was not. CONCLUSION: The tumor-to-vessel ratio may
      help to differentiate between hemangiomas and metastases. A ratio greater than
      0.98 allowed differentiating hemangiomas from metastases with a wide safety
      margin.

PMID- 16950696
TI  - Microinvasive ductal carcinoma arising within a fibroadenoma: A case report.
AB  - Fibroadenomas are among the most common benign breast tumors in which carcinomas
      rarely develop. We report the imaging findings of a microinvasive ductal
      carcinoma arising within a fibroadenoma in a 51-year-old woman. This mass showed
      coarse heterogeneous microcalcifications within a circumscribed mass on
      mammography, a heterogeneous hypoechoic mass on ultrasound, and an early
      enhancing mass on magnetic resonance imaging. Although a fibroadenoma in an older
      woman appears benign-looking, the presence of any unusual signs should raise
      concerns about malignancy.

PMID- 16950697
TI  - Adjusting the radioisotope tracer dose according to the body mass index does not
      enhance the visualization of axillary sentinel lymph nodes.
AB  - PURPOSE: To investigate whether the visualization of axillary sentinel nodes (SN)
      in the lymphoscintigraphy (LS) can be enhanced by adjusting the amount of
      radioactivity in accordance with the patient's body mass index (BMI). MATERIAL
      AND METHODS: Group I consisted of 356 consecutive breast cancer patients who
      underwent LS and SN biopsy after a single, intratumoral radioactive tracer
      injection with a median dose of 92 MBq. In group II (178 consecutive patients),
      the dose of the tracer was adjusted according to BMI; 80, 100, or 140 MBq.
      RESULTS: The visualization rate of axillary SN was 86% in group I and 83% in
      group II (P = 0.303). In patients with BMI >30 with visualized axillary SN, the
      median number of SN was 1 (1-4) in group I and 3 (1-7) in group II (P = 0.002).
      CONCLUSION: Adjusting the tracer dose in accordance with patient BMI did not
      enhance the visualization rate of axillary SN in LS.

PMID- 16950699
TI  - Detection of simulated microcalcifications in fixed mammary tissue: An ROC study
      of the effect of local versus global histogram equalization.
AB  - PURPOSE: To investigate whether sliding window adaptive histogram equalization
      (SWAHE) of digital mammograms improves the detection of simulated calcifications,
      as compared to images normalized by global histogram equalization (GHE). MATERIAL
      AND METHODS: Direct digital mammograms were obtained from mammary tissue phantoms
      superimposed with different frames. Each frame was divided into forty squares by
      a wire mesh, and contained granular calcifications randomly positioned in about
      50% of the squares. Three radiologists read the mammograms on a display monitor.
      They classified their confidence in the presence of microcalcifications in each
      square on a scale of 1 to 5. Images processed with GHE were first read and used
      as a reference. In a later session, the same images processed with SWAHE were
      read. RESULTS: The results were compared using ROC methodology. When the total
      areas AZ were compared, the results were completely equivocal. When comparing the
      high-specificity partial ROC area AZ,0.2 below false-positive fraction (FPF)
      0.20, two of the three observers performed best with the images processed with
      SWAHE. The difference was not statistically significant. CONCLUSION: When the
      reader's confidence threshold in malignancy is set at a high level, increasing
      the contrast of mammograms with SWAHE may enhance the visibility of
      microcalcifications without adversely affecting the false-positive rate. When the
      reader's confidence threshold is set at a low level, the effect of SWAHE is an
      increase of false positives. Further investigation is needed to confirm the
      validity of the conclusions.

PMID- 16950700
TI  - Impact of the number of readers on mammography interpretation.
AB  - PURPOSE: To evaluate the impact of the number of readers on sensitivity and
      specificity, and compare it with conference consensus reading. MATERIAL AND
      METHODS: Eight readers read mammography films of 200 women (including 35 false
      negative and 16 screen-detected cancers). The sensitivities and specificities of
      the two methods were calculated: either at least a single cancer-positive opinion
      within the group (summarized independent reading) or the cancer-positive opinion
      of the reader majority (conference consensus reading) was considered decisive.
      RESULTS: The mean sensitivity for summarized independent readings of different
      groups was 64.7% as compared to the 43.1% mean sensitivity of conference
      consensus readings. The mean specificities were 92.4% and 97.7%, respectively.
      The greatest sensitivity of 74.5% was achieved when the readings of the four best
      performing readers were combined. CONCLUSION: The sensitivity of reading is
      maximal when any positive opinion within a pair or a group of readers is taken
      into consideration. Discordant double reading may best be judged as screening
      positive, and the value of a third opinion should be questioned.

PMID- 16950701
TI  - The use of a polytetrafluoroethylene-covered stent graft for transjugular
      intrahepatic portosystemic shunt (TIPS): Long-term follow-up of 100 patients.
AB  - PURPOSE: To retrospectively evaluate results and clinical outcome of transjugular
      intrahepatic portosystemic shunt (TIPS) after implantation of a
      polytetrafluoroethylene (PTFE)-covered stent graft. MATERIAL AND METHODS: The
      stent graft was used in 112 patients with higher risk of primary (i.e. patients
      with Budd-Chiari syndrome) or secondary shunt failure (patients with occlusion of
      a previous uncovered stent), or a complicated TIPS procedure with an imminent
      technical complication requiring covered stent. Patients were scheduled at 3- to
      6-month intervals for duplex-sonographic control of shunt function. Radiological
      revision was performed in patients with a decrease in shunt function by >25%,
      primary non-response, or relapse of the index symptom. RESULTS: Twelve patients
      were lost to follow-up, and 100 patients were followed for 22+/-15 months. The
      actuarial rates of shunt patency were 90, 84, and 74% at 1, 2, and 3 years of
      follow-up, respectively. Two patients developed early (within 1 month) and 14
      patients late shunt failure. Except for one transient rise in liver enzymes due
      to outflow obstruction by the stent graft, no technical complications were seen.
      Primary response to treatment was seen in 97% of patients treated for variceal
      bleeding and 84% of patients treated for refractory ascites. A relapse of the
      index symptom was seen in 13% of bleeders and 9% of patients treated for
      refractory ascites. CONCLUSION: TIPS created with a PTFE-covered stent graft
      showed favorable long-term results.

PMID- 16950702
TI  - Percutaneous removal of two self-expanding stent grafts following failed
      deployment.
AB  - Insertion of self-expanding stent grafts was attempted in two patients with
      venous obstruction following unsuccessful venoplasty. One patient with end-stage
      renal disease had stenosis at the caudal end of the previously placed stent in
      the right external iliac vein. The second patient was treated for occlusion of
      multiple stents in the left iliac vein. Two of the stent grafts failed deployment
      and were subsequently removed percutaneously. New stent grafts were inserted in
      the intended positions. Despite additional venous access sites with large caliber
      sheaths, required for retrieval of the failed stent grafts, there were no major
      complications.

PMID- 16950703
TI  - Spontaneous pneumorrhachis in bronchial asthma.
AB  - We report on an 18-year-old male with bronchial asthma who presented with
      swelling over the neck and upper chest after a mild episode of bronchospasm.
      Physical examination was suggestive of subcutaneous emphysema, which was
      subsequently confirmed on a radiograph. Computed tomography in addition revealed
      pneumomediastinum and air within the epidural space of the spinal canal. Although
      spontaneous pneumomediastinum and subcutaneous emphysema have been described in a
      variety of situations, including patients with asthma, spontaneous pneumorrhachis
      in asthmatics is a very rare entity.

PMID- 16950704
TI  - Primary heart angiosarcoma detected by magnetic resonance imaging.
AB  - We present a case of primary heart angiosarcoma in a 38-year-old male. The
      patient presented with severe dyspnoe and arrhythmia. Echocardiography showed
      multiple solid masses in the pericardium and pericardial effusion. Chest
      radiography revealed left-sided pleural effusion and suspicion of a mass
      projected on the right atrium. Non-enhanced chest computed tomography raised the
      suspicion of a pericardial neoplasm projected on the right atrium adjacent to
      ascending aorta with markedly thickened pericardium and multiple round-shaped
      masses around the heart. Cardiac-gated magnetic resonance imaging demonstrated an
      inhomogeneous mass in the free wall of the right atrium adjacent to ascending
      aorta and multiple pericardial masses. Biopsy performed through thoracoscopy
      confirmed the diagnosis of a primary heart angiosarcoma.

PMID- 16950705
TI  - Multislice computed tomography coronary angiography at a local hospital: Pitfalls
      and potential.
AB  - PURPOSE: To evaluate whether the favorable results achieved with multislice
      computed tomography (MSCT) of coronary arteries at larger centers could be
      paralleled at a local hospital. MATERIAL AND METHODS: Fifty consecutive patients
      with suspected coronary artery disease scheduled for invasive investigation with
      quantitative coronary angiography (QCA) at a university hospital underwent MSCT
      with a 16-slice scanner at a local hospital. Diagnostic accuracy of MSCT for
      coronary artery disease was assessed using a 16-segment coronary artery model
      with QCA as the gold standard. RESULTS: Segments with diameter <2 mm, as defined
      by QCA, segments distal to occlusions, and stented segments were excluded. Of the
      remaining 489 segments, 73 (15%) were not assessable with MSCT. Sensitivity,
      specificity, and positive and negative predictive values for significant (>50%)
      stenosis for the 416 assessable segments were 92%, 82%, 53%, and 98%,
      respectively. CONCLUSION: Our beginners' experience demonstrated favorable
      results regarding sensitivity and negative predictive value. The positive
      predictive value, however, was unsatisfactory. Calcifications were identified as
      the most important factor for false-positive results with MSCT. With widespread
      use of MSCT coronary angiography, there is a risk of recruiting patients without
      significant coronary artery disease to unnecessary and potentially harmful
      invasive procedures.

PMID- 16950706
TI  - Thyroid ultrasound in diabetic patients without overt thyroid disease.
AB  - PURPOSE: To assess thyroid volume and to evaluate possible lesions in the gland
      structure using thyroid ultrasound in patients with diabetes mellitus type 1
      (DM1) and 2 (DM2) without overt thyroid disease. MATERIAL AND METHODS:
      Consecutive adult patients with DM2 (n = 98) and DM1 (n = 30) without overt
      thyroid disease referred to our department because of poorly controlled disease
      and/or diabetic complications were prospectively analyzed. Thyroid volumes, gland
      echogenicity, thyroid nodules incidence, and TSH levels were compared with
      control groups (n = 50 and 38) and matched according to sex and age. RESULTS:
      Significant increases in median thyroid volume were observed in both subjects
      with DM1 (17.3 cm3, interquartile range (IR) 13.9-21.6 cm3 versus 14.4 cm3, IR
      11.3-18.3 cm3; P < 0.05) and DM2 (20.5 cm3, IR 14.9-27.1 cm3 versus 14.1 cm3, IR
      11.3-18.3 cm3; P < 0.001) in comparison to their control groups. Moreover, in the
      population of type 2 diabetics, thyroid nodules (OR 2.37, 95% CI 1.14-4.93),
      parenchymatous goiter (OR 5.40, 95% CI 1.20-24.30), and all kinds of thyroid
      goiter according to the WHO definition (OR 4.18, 95% CI 2.02-8.66) were
      remarkably more frequent. In our patients, reduced (but within normal range) TSH
      level occurred in DM1 (median 0.97 mIU/l, IR 0.61-1.58 mIU/l versus median 1.66
      mIU/l, IR 0.76-2.09 mIU/l; P < 0.05). The presence of a negative linear
      correlation between thyroid volume and TSH concentration was noticed in patients
      with DM2 (RS = -0.38, P < 0.01). CONCLUSION: In individuals with DM1 and DM2
      treated for poorly controlled disease and/or diabetic complications, thyroid
      volumes were significantly higher than in the normal population. Moreover,
      nodular thyroid structure and parenchymatous goiter occurred more frequently in
      these type 2 diabetic patients.

PMID- 16950707
TI  - The iodinated radiographic contrast medium iohexol mimics the vasodilator effect
      seen with small increases in extracellular K+ in the isolated rabbit central ear
      artery.
AB  - PURPOSE: To investigate whether iodinated radiographic contrast media (IRCM)
      mimic the hyperpolarizing and vasodilator effects of K+ by comparing the
      vasodilator effect of a transient rise in extracellular K+ with that of the IRCM
      iohexol. MATERIAL AND METHODS: Immersed rabbit central ear arterial rings with
      and without endothelium and pre-contracted with phenylephrine (PE) were used to
      investigate the dependency of the endothelium in K+-induced vasodilatation.
      Perfused rabbit central ear arteries, pre-contracted with PE, were used to study
      the effects of bolus administrations of the IRCM iohexol or KCl on arterial tone
      under conditions that mimic those employed during clinical arteriography.
      RESULTS: A small rise in K+ caused an endothelium-independent and ouabain
      sensitive relaxation of PE-constricted rabbit central ear artery rings. The
      relaxation was not changed in the presence of barium. The IRCM iohexol and KCl,
      injected as boluses into perfused PE-constricted rabbit ear arteries, caused
      transient decreases in perfusion pressure. Iohexol- and K+-induced pressure
      decreases were significantly reduced in the presence of 10 microM ouabain alone
      or in combination with 30 microM barium. Neither iohexol- nor K+-induced pressure
      decrease was significantly changed in the presence of barium alone compared to
      controls. CONCLUSION: The vasodilator effect of IRCM mimics the vasodilator
      effect seen upon small increase in extracellular K+. Under the experimental
      conditions employed in the present study, a considerable part of the IRCM-induced
      vasodilatation appears to be due to activation of Na+/K+-ATPase in the smooth
      muscle cells.

PMID- 16950708
TI  - Use of 99mTc-mononuclear leukocyte scintigraphy in nosocomial fever.
AB  - PURPOSE: To determine the overall diagnostic accuracy of mononuclear leukocyte-
      99mTc scintigraphy in the routine detection of infectious lesions and fever of
      unknown origin (FUO) in inpatients. MATERIAL AND METHODS: The use of mononuclear
      leukocyte 99mTc scintigraphy is presented in 87 patients who fulfilled the Durack
      and Street diagnostic criteria of nosocomial FUO; 66 patients were suspected of
      having infectious lesions (myocarditis, endocarditis, infected catheters,
      diabetic foot, and osteomyelitis) and 21 patients presented with unknown causes
      of FUO. Scans were carried out 1, 3, and 24 h after injection of labeled
      leukocytes. RESULTS: In three cases (3/27) where scintigraphs were negative,
      biopsies were positive. There were two (2/87) false-positive scintigrams. We
      found a 95.8% sensitivity and 92.3% specificity. PPV was 93.8%, PPN 94.7%, and
      accuracy 94.2%. CONCLUSION: Mononuclear leukocyte 99mTc scintigraphy showed high
      sensitivity, specificity, positive and negative predictive values in patients
      with nosocomial FUO. These results suggest an important role for nuclear medicine
      in the management of patients with infection/inflammation.

PMID- 16950709
TI  - Static bone cavity of the mandible: Computed tomography findings with
      histopathologic correlation.
AB  - PURPOSE: To review computed tomography (CT) findings of histopathologically
      examined static bone cavities in order to determine whether an additional
      pathogenesis may play a role in this disease. MATERIAL AND METHODS: Four patients
      with histopathologically examined static bone cavities were included in this
      retrospective study. Location, appearance of bone remodeling, tissue
      characteristics, and contrast enhancement of the cavity were assessed on CT
      images. CT findings were then compared with the histopathological findings.
      RESULTS: Static bone cavity was found in the lingual molar region in three
      patients and in the lingual cuspid region of the mandible in one patient. Both
      fatty and soft tissues were present in the cavities of all four patients.
      Attenuation of the soft tissue in the cavities was found to be different from
      that of the submandibular gland. The soft tissue showed enhancement with contrast
      enhanced CT in three patients. For all patients, the histopathologic content of
      the static bone cavity included fat, soft tissue, and abnormal vasculature. The
      thickened vein wall in the abnormal vasculature was observed. Aberrant tissue of
      the submandibular gland was not found in any of the static bone cavities.
      CONCLUSION: Contrast enhancement of the soft tissue on the contrast-enhanced CT
      images suggests the presence of vasculature in the cavities. Histopathological
      examination confirmed the presence of fatty tissue and dilated abnormal vessels,
      and the absence of salivary gland tissue in the cavities. These findings show
      that vascular structures are prominent in tissues found in static bone cavities.

PMID- 16950710
TI  - Systematic analysis of missed extremity fractures in emergency radiology.
AB  - PURPOSE: To systematically analyze fractures in the extremities that were missed
      in the initial radiological report, primarily on plain radiographs, in the
      emergency department (ED). MATERIAL AND METHODS: From January 2003 to June 2004,
      2407 new patients were confirmed to have fractures in the extremities in the ED.
      A total of 3081 fractures were confirmed. In the initial radiological reports,
      115 fractures in 108 patients were missed. One musculoskeletal radiologist and
      one emergency radiologist independently carried out a second review of these
      images. The easily missed fracture sites were recorded. The possible reasons for
      misinterpretation were determined by consensus. RESULTS: The most frequent
      location for missed fractures, expressed as a percentage of all fractures in the
      same location, was the foot (7.6%), followed by the knee (6.3%), elbow (6.0%),
      hand (5.4%), wrist (4.1%), hip (3.9%), ankle (2.8%), and shoulder (1.9%). The
      average percentage for all missed fractures was 3.7%. On the second review, 70%
      of the initially missed fractures were identified. Analysis of the possible
      reasons for missed fractures showed the most common reason was subtlety of the
      fracture. CONCLUSION: The overall percentage of missed fractures in the
      extremities was 3.7%. Only 33% of the initially missed fractures were attributed
      to radiographically imperceptible lesions. Adequate training for physicians and
      radiologists in the ED may reduce the rate of missed fractures.

PMID- 16950711
TI  - Magnetic resonance signal, rather than tendon volume, correlates to pain and
      functional impairment in chronic Achilles tendinopathy.
AB  - PURPOSE: To depict abnormal tendon matrix composition using magnetic resonance
      imaging (MRI) in chronic Achilles tendinopathy, and correlate intratendinous
      signal alterations to pain and functional impairment. MATERIAL AND METHODS: MRI
      of the Achilles tendon was performed on 25 patients with chronic Achilles
      tendinopathy (median age 50, range 37-71 years). All patients suffered from pain
      in the mid-portion of the Achilles tendon. Intratendinous signal was calculated
      from five different sagittal sequences, using a computerized 3D seed-growing
      technique. Pain and functional impairment were evaluated using a questionnaire
      completed by patients. RESULTS: Severity of pain and functional impairment
      correlated to increased mean intratendinous signal in the painful tendon in all
      MR sequences (P < 0.05, median r = 0.38, range 0.28-0.43 for pain; P < 0.05,
      median r = 0.48, range 0.29-0.49 for functional impairment). However, tendon
      volume did not correlate to pain or functional impairment (P > 0.05). Difference
      in mean intratendinous signal between symptomatic and contralateral asymptomatic
      tendons was highly significant in all sequences (P < 0.05) except on T2-weighted
      images (P = 0.6). CONCLUSION: Severity of pain and disability correlated to
      increased MR signal rather than to tendon volume in patients with unilateral mid
      portion chronic Achilles tendinopathy.

PMID- 16950712
TI  - A simple technique for shoulder arthrography.
AB  - PURPOSE: To present a systematic approach to teaching a technique for
      arthrography of the shoulder. Using an adhesive marker-plate with radiopaque
      coordinates, precise sites for puncture can be identified and the need for
      fluoroscopic guidance obviated. MATERIAL AND METHODS: Forty-six glenohumeral
      arthrograms were performed in 45 patients; in 1 case involving examination of
      both shoulders. The stages of the technique are described in detail, as are the
      fundamental aspects of achieving an effective glenohumeral injection. Pain
      intensity was measured in all patients using a verbal description scale. RESULTS:
      Shoulder arthrography was successful in all cases. Average time taken for the
      procedure was 7 min, with no difference in the respective times required by an
      experienced radiologist and a resident. The procedure was well tolerated by most
      patients, with slight discomfort being observed in a very few cases. CONCLUSION:
      The arthrographic technique used in this study is simple, safe, rapid, and
      reproducible, and has the advantage of precise localization of the site for
      puncture without need for fluoroscopic guidance. The procedure described in this
      study can be of help in teaching residents and can reduce the learning curve for
      radiologists with no experience in arthrographic methods. It also reduces the
      time of exposure to fluoroscopy.

PMID- 16950713
TI  - Lumbar spinal dural arteriovenous fistula presenting with brainstem
      symptomatology: A case report.
AB  - This report is about a rare case of a lumbar spinal dural arteriovenous fistula
      (DAVF) with distant brainstem symptoms of vertigo and ataxia. Brain magnetic
      resonance imaging (MRI) demonstrated a high signal abnormality in the lower pons,
      medulla, and cervico-medullary junction, presumably related to venous
      hypertension. Spinal MRI revealed markedly dilated veins along the dorsal aspect
      of the cord, while spinal angiography confirmed the presence of a lumbar spinal
      DAVF. Because lumbar DAVF may cause remote brainstem symptoms, spinal DAVF should
      be considered in the differential diagnosis of high signal MRI abnormalities
      localized in the brainstem. Properly extending the scanning range is essential in
      the diagnosis.

PMID- 16950714
TI  - Role of diffusion-weighted magnetic resonance imaging in diffuse axonal injury.
AB  - PURPOSE: To determine whether the signal changes on magnetic resonance imaging
      (MRI), including fluid attenuated inversion recovery (FLAIR), T2*-weighted
      gradient echo (GE) imaging, and diffusion-weighted imaging (DWI) in diffuse
      axonal injury (DAI) patients correlate with the clinical outcome. MATERIAL AND
      METHODS: We diagnosed patients with DAI based on the following criteria: 1) a
      loss of consciousness from the time of injury that persisted beyond 6 h; 2) no
      apparent hemorrhagic contusion on computed tomography (CT); 3) the presence of
      white matter injury on MRI. Twenty-one DAI patients were analyzed (19 M, 2 F,
      mean age 34 years) with MRI (FLAIR, T2*-weighted GE imaging, and DWI). RESULTS:
      325 abnormalities were detected by MRI within a week after injury. The T2*
      weighted GE imaging was significantly more sensitive than FLAIR and DWI in
      diagnosing DAI. DWI detected only 32% of all lesions, but could depict additional
      shearing injuries not visible on either T2*-weighted GE imaging or FLAIR. The
      mean number of lesions in brainstem detected by DWI in the favorable group (good
      recovery/moderately disabled) was significantly smaller than in the unfavorable
      group (severely disabled/vegetative survival/death). This trend was not observed
      on the T2*-weighted GE imaging and FLAIR findings. CONCLUSION: DWI cannot detect
      all DAI-related lesions, but is a potentially useful imaging modality for both
      diagnosing and assessing patients with DAI.

PMID- 16950715
TI  - Radiological catheter drainage of abscesses in children.
AB  - PURPOSE: To assess the efficacy and safety of radiological catheter drainage of
      fluid collections and abscesses in children, and to review the principles,
      indications, technique, and possible complications of these procedures. MATERIAL
      AND METHODS: A retrospective analysis was made of all radiologically guided
      catheter placements performed between March 1999 and April 2003. Patients' age,
      sex, location of the collection, technical details of the procedure, including
      modality used for guidance, technique of placement, type of catheter used,
      catheter indwelling time, and time for temporization were recorded from chart
      reviews. Success rate was calculated based on the number of curative drainage
      procedures. RESULTS: 33 children (16 boys and 17 girls) aged between 7 days and
      14 years of age (mean 7 years) underwent 37 procedures. Successful drainage was
      achieved in 31 of 33 patients (94%). The dwell time for catheters ranged between
      1 day and 30 days (mean 5.7 days). Mean duration for defervescence was 2 days.
      There were no major complications. CONCLUSION: Imaging-guided catheter drainage
      of fluid collections in children is safe and effective. Newer approaches, better
      imaging, and improved techniques have resulted in improved cure rates. The basic
      principles, common indications, various techniques, and the possible
      complications of these procedures, with special reference to the pediatric
      population, are reviewed in this article.

PMID- 16950716
TI  - Thin-section axial multidetector computed tomography and multiplanar reformatted
      imaging of children with suspected foreign-body aspiration: Is virtual
      bronchoscopy overemphasized?
AB  - PURPOSE: To determine the added value of multidetector computed tomography (MDCT)
      assisted virtual bronchoscopy (VB) to axial MDCT and multiplanar reformatted
      (MPR) imaging with respect to conventional bronchoscopy in the evaluation of
      children with suspected foreign-body aspiration (FBA). MATERIAL AND METHODS:
      Twenty-one consecutive children (14 male, seven female, age 8 months-7 years,
      mean age 3.5 years) presenting with the suspicion of FBA were examined with 16
      slice MDCT using 100-120 kV, 30-50 mA, 1-mm section thickness, 1.2 pitch ratio,
      and 0.6-1.0-mm reconstruction interval. Before CT examinations, chest
      radiographies were also obtained in all cases. VB and MPR imaging were carried
      out after MDCT examinations. RESULTS: Nine foreign bodies were identified by gold
      standard conventional bronchoscopy. VB, thin-section axial MDCT, and MPR images
      identified eight of nine foreign bodies. CT scans with MPR images and VB did not
      reveal a chronic foreign body; and, in one patient, endobronchial mucous was
      diagnosed as the foreign body. The sensitivity, specificity, and accuracy of thin
      section axial MDCT and MPR images alone in the diagnosis of FBA were 88.9%,
      91.7%, and 90.5%, respectively. Results were the same as those obtained when VB
      was also included. CONCLUSION: MDCT with VB and axial/MPR images provide equally
      valuable information in children with suspected foreign-body aspiration and
      prevent unnecessary conventional bronchoscopic examinations. However, VB
      increases total examination time and cost, and it does not provide additional
      information over MPR images in the evaluation of foreign-body aspiration.

PMID- 16950717
TI  - Renal capsular leiomyoma: Report of a case with unusual CT appearance.
AB  - Clinically symptomatic renal capsular leiomyomas are rare. Previous research has
      shown that these tumors are usually well-defined cystic lesions, solid lesions,
      or a mixture of the two. We report an unusual case of renal capsular leiomyoma
      which was well defined by ultrasonography, but lacked a well-defined edge in CT.
      The reason for the absence of a well-defined tumor edge is probably due to
      degeneration in certain parts of the tumor resulting in a different degree of
      enhancement. Thus, the possibility of renal capsular leiomyoma should be included
      in the differential diagnosis whenever a renal mass is found, especially when
      either CT or ultrasonography shows that the tumor has a smooth, well-defined
      contour.

PMID- 16950719
TI  - The effect of joystick handle size and gain at two levels of required precision
      on performance and physical load on crane operators.
AB  - The study was designed to determine the effect of joystick handle size and
      (display-control) gain at two levels of required task precision on performance
      and physical load on crane operators. Eight experienced crane operators performed
      a simulated crane operation task on a computer by use of a joystick with either a
      short or a large handle. The task was performed at three gain levels and at two
      levels of required precision. Task performance, wrist and forearm postures, upper
      extremity muscle activity, perceived exertion and perceived comfort were
      measured.Task performance improved when using the joystick with the short handle
      and when working at a higher gain, while physical load decreased or remained the
      same. An increased level of required task precision was associated with a lower
      performance, but physical load was not affected. External validity of the
      simulated crane task seemed sufficient enough to extrapolate the results to
      practice.A joystick with a short handle is recommended, as this leads to an
      increased performance whilst the operator's physical load decreases or remains
      the same. Further optimization of performance and physical load can be achieved
      by optimizing gain settings of the joystick in relation to the task and type of
      joystick used.

PMID- 16950720
TI  - The relationship between shoulder torques and the perception of muscular effort
      in loaded reaches.
AB  - The objective of this study was to define the quantitative relationship between
      external dynamic shoulder torques and calibrated perceived muscular effort levels
      for load delivery tasks, for application in job analyses. Subjects performed a
      series of loaded reaches and, following each exertion, rated their perceived
      shoulder muscular effort. Motion and task physical requirements data were
      processed with a biomechanical upper extremity model to calculate external
      dynamic shoulder torques. Calculated torque values were then statistically
      compared to reported calibrated perceived muscular effort scores. Individual
      subject torque profiles were significantly positively correlated with perceived
      effort scores (r2 = 0.45-0.77), with good population agreement (r2 = 0.50). The
      accuracy of the general regression model improved (r2 = 0.72) with inclusion of
      factors specific to task geometry and individual subjects. This suggests two
      major conclusions: 1) that the perception of muscular shoulder effort integrates
      several factors and this interplay should be considered when evaluating tasks for
      their impact on the shoulder region; 2) the torque/perception relationship may be
      usefully leveraged in job design and analysis.

PMID- 16950721
TI  - Musculoskeletal disorders among female and male air traffic controllers
      performing identical and demanding computer work.
AB  - Operators with identical, demanding computer work (90 female and 97 male air
      traffic controllers) were found to have high prevalences of disorders (assessed
      by questionnaire and physical examination) in neck, shoulders and upper back. In
      spite of the identical work, the women displayed higher prevalences than the men
      (e.g. neck diagnoses 21% vs. 4%). Disorders in elbows, wrists and hands were less
      common, with similar rates in both genders. Generally, the psychosocial work
      environment (assessed by questionnaire) was found to be good, but with large
      inter-individual variation. Women experienced lower decision latitude than men,
      particularly regarding influence and freedom at work, but perceived higher social
      support. Physically, the work was characterized by relatively low angular
      velocities of upper arms (measured by inclinometry) and wrists (right: < 1
      degrees/s during 19% of time, measuring by goniometry), dynamic muscular
      activities and high time fractions of rest in the trapezius and forearm extensor
      muscles (measuring by electromyography). There were only minor differences
      between the genders.

PMID- 16950722
TI  - The effect of speech and speech intelligibility on task performance.
AB  - The aim of this study was to find out what are the effects of three different
      sound environments on performance of cognitive tasks of varying complexity. These
      three sound environments were 'speech', 'masked speech' and 'continuous noise'.
      They corresponded to poor, acceptable and perfect acoustical privacy in an open
      plan office, respectively. The speech transmission indices were 0.00, 0.30 and
      0.80, respectively. Sounds environments were presented at 48 dBA. The laboratory
      experiment on 36 subjects lasted for 4 h for each subject. Proofreading
      performance deteriorated in the 'speech' (p < 0.05) compared to the other two
      sound environments. Reading comprehension and computer-based tasks (simple and
      complex reaction time, subtraction, proposition, Stroop and vigilance) remained
      unaffected. Subjects assessed the 'speech' as the most disturbing, most
      disadvantageous and least pleasant environment (p < 0.01). 'Continuous noise'
      annoyed the least. Subjective arousal was highest in 'masked speech' and lowest
      in 'continuous noise' (p < 0.05). Performance in real open-plan offices could be
      improved by reducing speech intelligibility, e.g. by attenuating speech level and
      using an appropriate masking environment.

PMID- 16950723
TI  - Measures of localized spinal muscle fatigue.
AB  - The objective of this study was to determine the best variable, if any, to
      indicate the level of localized muscle fatigue. Six male and six female subjects
      were studied while they exerted their maximal voluntary contraction and 40% of
      maximal voluntary contraction of spinal extensors in an isometric lifting
      activity. The electromyography (EMG) of erectores spinae at thoracic and lumbar
      levels was measured bilaterally. Also, the muscle bed blood volume, level of
      blood oxygenation to erector spinae at L3 level and heart rate were measured. The
      initial and final values of subjective feelings of fatigue through visual
      analogue score, rate of perceived exertions and body part discomfort rating were
      recorded. The mean maximal voluntary contraction forces for males and females
      were 899 (238) N and 431 (135) N respectively. The mean durations of hold in
      maximal voluntary fatiguing contraction were 68.1 (39.9) s and 72.3 (37.0) s for
      men and women respectively. By the end of the hold the force declined to 52% for
      males and 62% for females. The EMG amplitudes and median frequencies also
      progressively declined (p < 0.01). ANOVA revealed that the task percentile values
      of all variables were significantly different (p < 0.01). Gender had a
      significant main effect (p < 0.01). The correlation coefficients between force
      and other individual variables were weak to modest, but significant (p < 0.001).
      None of the single variables predicted fatigue reliably for either gender and
      levels of contraction. The regression equations developed were highly significant
      (p < 0.01) and they explained 96 to 98% of variance in both genders and
      contractions.

PMID- 16950724
TI  - A comparison between intermittent and constant wheelchair propulsion strategies.
AB  - The purpose of this study was to investigate the effect of different synchronous
      push strategies on physiological parameters and temporal timing characteristics.
      Eight novice male able-bodied participants completed four counter-balanced
      conditions: two push strategies (constant pushing) and intermittent pushing (INT)
      at two push frequencies (40 and 70 pushes/min) at 27 W. The ANOVA main effects
      for frequency indicated that regardless of push strategy, oxygen cost and
      mechanical efficiency increased with an increase in push frequency (p < 0.01).
      The INT40 strategy resulted in the lowest heart rate (115 +/- 19 beats/min). With
      increased frequency the push angle was reduced (91 degrees vs. 78 degrees
      respectively) and the push was initiated at a more anterior position of the wheel
      (p < 0.05). The results suggest that regardless of push strategy, the over-riding
      factor that influences both the physiological and timing parameters measured was
      push frequency.

PMID- 16950726
TI  - Time for a routine immunization communication effort.

PMID- 16950725
TI  - Prediction of forearm muscle activity during gripping.
AB  - Occupational exposure is typically assessed by measuring forces and body postures
      to infer muscular loading. Better understanding of workplace muscle activity
      levels would aid in indicating which muscles may be at risk for overexertion and
      injury. However, electromyography collection in the workplace is often not
      practical. Therefore, a set of equations was developed and validated using data
      from two separate days to predict forearm muscle activity (involving six wrist
      and finger muscles) from grip force and posture of the wrist (flexed, neutral and
      extended) and forearm (pronated, neutral, supinated). The error in predicting
      activation levels of each forearm muscle across the range of grip forces, using
      the first day data (root mean square error; RMSEmodel), ranged from 8.9% maximal
      voluntary electrical activation (MVE) (flexor carpi radialis) to 11% MVE
      (extensor digitorum communis). Grip force was the main contributor to predicting
      muscle activity levels, explaining over 70% of the variance in flexor activation
      levels and up to 60% in extensor activation levels, respectively. Inclusion of
      gender as a variable in the model improved estimates of flexor but not extensor
      activity. While posture itself explained minimal variance in activation without
      grip force (< 10% MVE), wrist and forearm posture were required (with grip force)
      to explain over 70% of the variance of all six muscles. The validation process
      indicated good day-to-day reliability of each equation, with similar error for
      flexor muscle models but slightly higher error in the extensor models when
      predicting activity levels for the second day of data (RMSEvalid ranging from
      8.9% to 12.7% MVE). Detailed error analysis during validation revealed that
      inclusion of posture in the model effectively decreased error at grip forces
      above 25% maximum, but was detrimental at very low grip forces. This study
      presents a potential new tool to estimate forearm muscle loading in the workplace
      using grip force and posture, as a surrogate to use of a complex biomechanical
      model.

PMID- 16950727
TI  - Approaches to improving health literacy: lessons from the field.

PMID- 16950728
TI  - The importance of establishing regimen concordance in preventing medication
      errors in anticoagulant care.
AB  - Miscommunication between patients and providers can have serious consequences,
      especially where medications are concerned. We examined whether regimen
      discordance between patient and provider, a possible result of miscommunication,
      contributes to unsafe medication management. We studied 220 patients taking
      warfarin in an anticoagulation clinic to characterize two medication assessment
      methods. We measured (1) adherence by asking patients to report any missed doses
      and (2) concordance between patients' and providers' reports of warfarin
      regimens. We categorized patients as having regimen adherence if they missed no
      doses, and concordance if there was patient-provider agreement in weekly dosage.
      We characterized anticoagulant outcomes as unsafe if international normalized
      ratio (INR) values were <2.0 (at risk for thrombosis) or >4.0 (at risk for
      hemorrhage), and explored relationships among adherence, concordance, and
      anticoagulant outcomes. One hundred fifty-five patients (71%) reported no missed
      doses during the prior 30 days. Poor adherence was associated with
      underanticoagulation (AOR 2.33, 1.56-3.45), but not overanticoagulation (AOR
      1.36, 0.69-2.66). One hundred ten patients (50%) reported regimens discordant
      with clinicians' report. There was no relationship between patients' reports of
      adherence and concordance. Among adherent patients, discordance was associated
      with underanticoagulation (AOR 1.67, 1.00-2.78) and overanticoagulation (AOR
      3.44, 1.32-9.09). Discordance regarding warfarin regimens is common and places
      patients at risk for adverse events. To promote safe and effective care,
      clinicians should separately determine adherence and regimen concordance during
      routine medication assessments. Systems need to be developed to ensure
      concordance in medication regimens.

PMID- 16950729
TI  - The influence of graphic format on breast cancer risk communication.
AB  - Graphic displays can enhance quantitative risk communication. However, empiric
      data regarding the effect of graphic format on risk perception is lacking. We
      evaluate the effect of graphic format elements on perceptions of risk magnitude
      and perceived truth of data. Preferences for format also were assessed.
      Participants (254 female primary care patients) viewed a series of hypothetical
      risk communications regarding the lifetime risk of breast cancer. Identical
      numeric risk information was presented using different graphic formats. Risk was
      perceived to be of lower magnitude when communicated with a bar graph as compared
      with a pictorial display (p < 0.0001), or with consecutively versus randomly
      highlighted symbols in a pictorial display (p = 0.0001). Data were perceived to
      be more true when presented with random versus consecutive highlights in a
      pictorial display (p < 0.01). A pictorial display was preferred to a bar graph
      format for the presentation of breast cancer risk estimates alone (p = 0.001).
      When considering breast cancer risk in comparison to heart disease, stroke, and
      osteoporosis, however, bar graphs were preferred pictorial displays (p < 0.001).
      In conclusion, elements of graphic format used to convey quantitative risk
      information effects key domains of risk perception. One must be cognizant of
      these effects when designing risk communication strategies.

PMID- 16950730
TI  - Sex education and the news: lessons from how journalists framed virginity
      pledges.
AB  - This analysis of newspaper articles about virginity pledges published from 1987
      to 2001 describes prominent news frames on sex education. The articles focused on
      True Love Waits, a nationwide virginity pledge campaign encouraging abstinence,
      and results from Add Health (TLW), a longitudinal study that included questions
      to evaluate the effects of virginity pledges. Our results show how news frames
      and sources can vary for related events. Reporting on virginity pledges was often
      not grounded in science, and reporting on the science of pledges did not reflect
      a broader context. In this case, reporting may have encouraged support for
      abstinence-only programs.

PMID- 16950731
TI  - Improving the way we die: a coorientation study assessing agreement/disagreement
      in the organization-public relationship of hospices and physicians.
AB  - The movement to reform dying in America promotes hospice as a model for change.
      Yet terminally ill patients increasingly are closer to death when they enter some
      3,300 hospices. Hospice leaders blame physicians for delaying referrals and
      charge that delays cause hardships for their organizations and patients. Based on
      symmetrical theory and the coorientation model, a survey of one Southern hospice
      and its referring physicians was conducted to measure agreement, perceived
      agreement, and accuracy between the two sides on the issue of timely referral.
      Results showed that hospice leaders inaccurately perceive a high degree of
      disagreement when they and physicians generally agree on the issue.

PMID- 16950733
TI  - Responsiveness of functional health status measures frequently used in stroke
      research.
AB  - PURPOSE: To compare the responsiveness of several functional health status
      measures frequently used in stroke research, namely the Barthel Index (BI),
      Functional Independence Measure (FIM), Frenchay Activities Index (FAI) and Stroke
      Adapted Sickness Impact Profile 30 (SA-SIP 30). METHOD: Patients with a first
      ever supratentorial stroke admitted for inpatient rehabilitation were included.
      Complete datasets for 163 patients were available for analysis. Floor/ceiling
      effects and responsiveness, quantified by effect sizes, were studied for the
      periods between rehabilitation admission and six months post stroke (subacute
      phase) and between six and 12 months post stroke (chronic phase). RESULTS: Effect
      sizes in the subacute phase were similar and were classified as large for the BI,
      FIM total and FIM motor score. The FIM cognitive score showed a considerable
      ceiling effect and had the smallest effect size in the subacute phase. In the
      chronic phase, the FAI and SA-SIP 30 detected the most changes and had moderate
      effect sizes. CONCLUSIONS: BI, FIM total and FIM motor score, FAI and SA-SIP 30
      were responsive measures. We recommend the use of the BI in the subacute phase
      and the use of the FAI and SA-SIP 30 in the chronic phase, especially for the
      stroke rehabilitation population.

PMID- 16950734
TI  - Perceptions of patient education in spinal cord injury rehabilitation.
AB  - PURPOSE: Patient education is a key part of spinal cord injury (SCI)
      rehabilitation with the goal of preparing persons with SCI to meet life's daily
      challenges. The purpose of this study was to evaluate experiences of the patient
      education program from the patients' perspective. METHODS: The qualitative design
      of this study involved a semi-structured interview format to gather descriptive
      information relevant to the aspects of the patient education program identified
      to facilitate or impede learning. Twenty-two patients participated in the
      individual interviews. RESULTS: The framework that emerged from the analysis of
      the interview transcripts included a total of six main categories, two
      subcategories and two main themes. There were two central categories of Need to
      know and Information access and delivery that were influenced by categories of:
      Learning readiness, Learning affects, Problem exploration and Family involvement.
      The category of Information access and delivery included two subcategories
      labeled Resources and Learning strategies. From these categories the main themes
      of Learning partnership and Individuality were identified. CONCLUSIONS: This
      research provides valuable information from the patients' perspective that may be
      used to enhance patient education programs. The importance of incorporating
      principles of adult learning is highlighted.

PMID- 16950735
TI  - Stroke patients' experiences of return to work.
AB  - Purpose. The aim of this study was to describe the experience of return to work
      (RTW) after stroke from the patient's perspective.Method. Six patients who had
      their first ever stroke in 2001, were <65 years of age and were working at the
      time of their stroke were included. Information was obtained via an open-ended
      interview. The material was transcribed verbatim and analysed using Giorgi's
      empirical phenomenology.Results. Rehabilitation was perceived as primarily aimed
      at restoring bodily functions and a return to everyday activities, rather than at
      promoting a return to work. It was not experienced as adapted to the
      participants' needs or their age. The workplace was experienced as very important
      in the rehabilitation process. When the informants experienced that the
      rehabilitation professionals were not taking action, they took control of the
      situation themselves. The informants expressed pride in their own capacity to
      take the initiative and in their ability to take action. Both self-employed and
      employed informants said they had possibilities and opportunities to take action
      since their work situation was flexible. The informants' adaptation to a new role
      at work was perceived as facilitated by the understanding and positive attitude
      of co-workers.Conclusion. Among this group of stroke patients, the individual
      patient's capacity and ability to return to work was enhanced by motivation or
      "will" and self-efficacy in combination with external support. Self-efficacy was
      not only a personal trait or internal factor; it was enhanced and encouraged in
      interaction with contextual conditions. There are similarities between the RTW
      process and processes of health promotion.

PMID- 16950736
TI  - Personal assistance, adaptations and participation in students with cerebral
      palsy mainstreamed in elementary schools.
AB  - PURPOSE: The aims of this study were to examine differences in level of
      participation of students with CP in full inclusion (FI group) as compared to
      self-contained classes (SC group), differences in the task supports provided for
      these two groups, the interrelationships between assistance and adaptation
      provided and the differential impact of physical task supports vs.
      cognitive/behavioural task supports on participation. METHOD: 148 elementary
      school students were divided into two groups: 100 fully included (FI) students
      with CP, and 48 students with CP in self-contained classes (SC). The School
      Function Assessment (SFA) was used as the main measurement for assessing the
      levels of participation and functional performance profiles. RESULTS:
      Statistically significant differences (p < 0.0001) were found between the two
      groups on all scales (physical and cognitive/behavioural assistance and
      adaptations). Supports provided to the SC group were significantly greater than
      to the FI group and physical task supports provided to both groups were
      significantly greater than cognitive/behavioural supports. Pearson correlations
      and Smallest Space Analyses (SSA) revealed significant (p < 0.01) moderate to
      strong correlations (0.57 > r < 0.77) between all four task supports, and between
      provided task supports and participation (0.66 > r < 0.82). CONCLUSIONS: This
      study's focus enhances our understanding of the impact of task supports to the
      various factors contributing to the dimensions of the ICF, as well as their
      interrelationship with participation. Devises and cognitive and behavioural
      adaptations are required in a wider manner in addition or alternative to physical
      assistance by adults if we are to increase the chance of students with severe CP
      to become participatory for academic and social tasks required in school.

PMID- 16950737
TI  - The Spine Team Assessment for chronic back pain disability. Part 1: basic
      protocol and performance in 500 patients.
AB  - PURPOSE: For persons with chronic back pain disability, customized, effective,
      and efficient treatment depends on the initial assessment. Functional capacity
      evaluations and intake screenings for particular programs are not independent or
      goal-directed. This paper describes a standardized independent multidisciplinary
      assessment for treatment planning, and characteristic findings in a population of
      chronically disabled persons. METHODS: The Spine Team Assessment (STA), a (1/2)
      day assessment including extensive intake information, evaluations by therapists
      and counselors, a team meeting with a physician, and a comprehensive report, was
      performed on 500 consecutive persons with chronic back pain. RESULTS:
      Representative findings included maximum cardiac performance of 5.33 (+/-4.08 SD)
      METS; Progressive Isoinertial Lifting Evaluation floor-to-waist of 36.4% (+/
      23.9% of norms, and CESD depression scores of 24.7 (+/-13.5 SD). Fear and
      avoidance and poor physiologic effort were common. CONCLUSION: Deconditioning,
      psychosocial factors and functional deficits are common, complex, and variable
      among chronic back pain patients. This description of the STA provides a
      potentially reproducible standard for research into individualized treatment. The
      work provides benchmark data for independent multidisciplinary assessments.

PMID- 16950738
TI  - The Spine Team Assessment for chronic back pain disability. Part 2: team decision
      making and a preliminary outcome study.
AB  - PURPOSE: Back pain disability is complex, involving medical, physical,
      functional, social, and financial issues. This study aims to develop the first
      codified decision making process for individualized treatment planning. METHODS:
      In a multidisciplinary assessment protocol for chronic low back pain disability,
      the Spine Team Assessment (see Part I), a 'case law' qualitative approach to
      decision making began with a basic framework. Details were established over 103
      cases at a community hospital. Through 500 more cases, a university spine program
      developed new exceptions, definitions, and rule clarifications. RESULTS: The
      final framework includes physical deconditioning, psychosocial factors, and
      potential for cure, with dozens of subcategories. Seventeen different
      combinations of therapy were recommended. Of 68 persons referred to one
      multidisciplinary treatment protocol, at 6 - 12 months the 17 completers had less
      work disability (31 vs. 62%, p = 0.032) and tended towards fewer subsequent
      diagnostic tests (17.6 vs. 34.7%) and less surgery (0 vs. 4). CONCLUSIONS: The
      data suggests that the process is complex, that customization did occur, and that
      at least one team decision led to better outcomes. While derived qualitatively,
      this decision-making tree provides a road map for less experienced teams and a
      precedent for researchers who wish to study individualized treatment.

PMID- 16950739
TI  - Use of the ICF in identifying factors that impact participation in physical
      activity/rehabilitation among people with disabilities.
AB  - Many health professionals have expressed difficulty finding ways to keep people
      with disabilities engaged in community-based physical activity/rehabilitation
      programs. A major reason for this low adherence may be that the recommended
      intervention plan does not match well with the specific needs of the individual.
      Various personal and/or environmental factors along with the person's level of
      functioning can impede participation in healthful physical
      activity/rehabilitation. The International Classification of Functioning,
      Disability and Health (ICF) can be a useful tool for identifying key factors
      associated with participation in community-based physical
      activity/rehabilitation. The ICF allows health professionals to identify the
      level of functioning at the body, person and societal level, as well as
      understand the person-environment contextual factors that may impede or enhance
      participation. This paper describes how the ICF can assist health professionals
      in identifying a broader constellation of factors when prescribing physical
      activity/rehabilitation programs for persons with varying levels of disability.

PMID- 16950740
TI  - Time for a shift in Australian rehabilitation?
AB  - PURPOSE: Tertiary rehabilitation, particularly in Australia, still costs a
      significant amount of money each year. Turnover in the rehabilitation industry is
      extremely high and rehabilitation professionals report being dissatisfied in
      their work. These ironic findings can be attributed to the state of tension in
      which rehabilitation finds itself. A decade ago, it was noted that tertiary
      rehabilitation counselling was facing the challenge of managing several
      conflicting forces and constantly shifting priorities. In the last decade, this
      challenge has intensified. METHOD: A review of current data was undertaken to
      identify the primary tensions that have influenced rehabilitation over the last
      decade. RESULTS: Tensions were attributed to three sets of opposing forces
      related to the philosophy of rehabilitation, the economic imperative and the role
      of privatisation of the industry. CONCLUSION: This paper argues the need for a
      fundamental shift in thinking if the rehabilitation discipline is to continue
      growing. Precedents exist that can assist rehabilitation to make a significant
      shift to a new model of thinking, but a great deal of attention must be focused
      on the legal, economic and medical barriers to that movement.

PMID- 16950741
TI  - The influence of adaptation on visual motion detection in chronic sixth nerve
      palsy after treatment with botulinum toxin.
AB  - PURPOSE: To investigate changes in visual motion perception after treatment with
      botulinum toxin in patients with unilateral chronic lateral rectus muscle palsy.
      METHODS: Five patients and control subjects were asked to report the perceived
      drift direction of a sinusoidal grating that was initially stationary and then
      began to accelerate at 0.09 degrees /sec2 in a horizontal direction. The grating
      had a field size of 18.5 degrees and was presented monocularly with a contrast
      just above threshold for visibility for central vision. Both the paretic and non
      affected eyes were tested. Psychophysical testing was performed under the
      following conditions: 1) before treatment and testing, patients occluded their
      paretic eye for at least three days to avoid diplopia. 2) After treatment with
      botulinum toxin, alignment was corrected and patients stopped occluding their
      paretic eye for at least three days before testing. The control subjects occluded
      their non-dominant eye for three days before testing. RESULTS: In condition 1, no
      differences in motion detection values between patients and control subjects were
      found. In condition 2, motion detection thresholds were raised approximately 0.15
      degrees /sec as compared to pre-treatment values and compared to the control
      group. CONCLUSIONS: After treatment, a raised threshold for motion detection is
      one mechanism used to avoid oscillopsia and visuo-vestibular disorientation
      during head movements in patients with chronic paralytic squint. This study lends
      evidence that perceptual-adaptive, compensatory mechanisms develop to reduce
      oscillopsia and disorientation rather than being caused by abnormal cortical
      motion processing or defective eye muscle action.

PMID- 16950742
TI  - Intra-individual variability of saccadic velocity measured with the infrared
      reflection and magnetic scleral search coil methods.
AB  - BACKGROUND: The infrared (IR) and the magnetic scleral search coil (MSC) systems
      for eye tracking were studied with regard to the intra-individual variability in
      saccadic eye movement recordings. METHOD: Three healthy subjects performed
      similar saccadic eye movement tasks at five different occasions with both the IR
      (Orbit XY-1000) and the MSC (Skalar Medical) techniques. The maximum velocity
      (VMAX) and slope constant (C) of the main sequence plots were analyzed with
      regard to the coefficient of variation (CV) and the intraclass correlation
      coefficient (Ricc). In addition, the possible reasons for variability in the IR
      recordings, especially different causes for noise, were analyzed and discussed.
      RESULTS: The main sequence data showed intra-individual variation with both
      recording systems, but the coefficient of variation was higher for VMAX with the
      IR compared to the MSC method. Ricc analysis showed that 36% of the variance of
      VMAX and 49% of the variance of C resulted from intra-individual variability in
      recordings of the IR system. The corresponding results for the MSC recordings
      regarding VMAX and C were 48% and 88%. CONCLUSIONS: Saccadic eye movement
      recordings yielded a larger intra-individual variability with the IR system than
      with the MSC system. The effect that the MSC annulus may have on the ocular motor
      command signal and the possible low pass filter caused by the coil slipping on
      the surface of the eye may partly explain the relatively lower velocity in the
      MSC recordings. Also, noise in the IR recordings induces peaks of eye velocity,
      which can be reduced considerably by filtering. However, the variability in the
      recordings, which was larger in the IR than in the MSC recordings, did not seem
      to be decreased by filtering. The basic level of noise in the recordings was not
      clearly associated with the amount of reduction of VMAX when the IR recordings
      were filtered. We suggest that artefacts of the saccadic signal, which can be
      related to changes in the reflecting surface of the eyes and eyelids, are
      important factors for explaining the variability and high-velocity peaks in the
      IR recordings. Lighting conditions was confirmed as a cause for noise, but
      temperature and air humidity changes in the goggles were not suspected to
      influence data in the normal experimental setting. Although noise, shortcomings
      of the recording technique and procedure may offer explanations for the intra
      individual variability, the calibration procedure and changes in attention and
      fatigue of the subject should also be considered.

PMID- 16950743
TI  - An office-based scale for assessing control in intermittent exotropia.
AB  - INTRODUCTION: Although intermittent exotropia may deteriorate with time, there
      are no widely accepted criteria for measuring progression in this disorder. The
      purpose of this study was to prospectively evaluate a new scale for assessing the
      level of control in children with intermittent exotropia. METHODS: Thirty
      consecutive pediatric patients (< 14 years) with intermittent exotropia were
      prospectively evaluated from July 1, 2004 through June 30, 2005 using a new scale
      to assess the level of control for both distance and near fixation. The distance
      score (0 to 5) was combined with the near score (0 to 5) to yield an overall
      control score from 0 to 10. RESULTS: The 30 patients were examined at a median
      age of 72 months (range, 15 months to 13 years). The level of control at distance
      was worse than or equal to the near level of control in all 30 patients. The
      control scores ranged from 0 to 5 for distance and 0 to 4 for near, with an
      overall control score ranging from 0 to 8 (median of 3). CONCLUSIONS: This new
      scale for assessing control in children with intermittent exotropia can be easily
      applied in the office setting and characterizes the wide range of control in this
      disorder.

PMID- 16950744
TI  - Results of compensatory extraocular muscle surgery after macular translocation.
AB  - PURPOSE: Macular translocation is an optional surgical treatment for age-related
      macular degeneration. However, this technique induces postoperative torsional
      complaints and surgical counterrotation of the globe is mandatory. The purpose of
      this study is to report the effect of compensatory extraocular muscle surgery
      upon the torsional complaints in patients who underwent a macular translocation
      procedure. DESIGN: The pre- and postoperative data on the first 35 patients in
      our department who underwent a counterrotation procedure after macular
      translocation surgery are reviewed. METHODS: From November 2001 to January 2005,
      35 patients underwent a macular translocation procedure, with subsequent
      extraocular muscle surgery to counterrotate the eye. Three types of rectus muscle
      transposition procedures were used: full-tendon transposition of two opposite
      rectus muscles, "crossed" half-tendon transposition of all rectus muscles ('split
      & cross' procedure), and "uncrossed" half-tendon transposition of all rectus
      muscles ('split & neighbor cross' procedure). In the majority of patients these
      procedures were associated with oblique muscle surgery. RESULTS: With the
      selected procedures, retinal excyclodeviations are easier to correct then retinal
      incyclodeviations. In our hands, full-tendon transposition of two opposite rectus
      muscles with or without associated oblique muscle surgery, never corrects more
      than 30 degrees. 'Split & cross' procedures combined with oblique muscle surgery
      are sufficient for retinal excyclodeviations of 30-45 degrees and for
      incyclodeviations of up to 30 degrees; 'split & neighbor cross' procedures
      combined with oblique muscle surgery are sufficient for retinal excyclodeviations
      of 45-65 degrees and for incyclodeviations of up to 40 degrees . CONCLUSIONS: The
      effect of the various procedures appears to be predictable. It is possible to
      select a surgical procedure as a function of the amount of retinal
      cyclodeviation.

PMID- 16950745
TI  - Inadvertent scleral perforation in eye muscle versus retinal detachment buckle
      surgery.
AB  - PURPOSE: Inadvertent scleral perforation is a recognized complication of eye
      muscle and retinal detachment buckle surgery. If these operations are performed
      by the same surgeon, it is unknown which of these procedures has a higher risk of
      scleral perforation. METHODS: In the period from 1999 until 2004, 427 eyes of 317
      patients were operated using eye muscle surgery and 81 eyes of 80 patients with
      retinal detachment buckle surgery. All operations were performed by the same
      surgeon (JK). In a retrospective, single-center, comparative, observational
      study, the records of these patients were assessed to determine the number of
      scleral perforations with retinal damage or drainage of subretinal fluid.
      RESULTS: In the group receiving retinal detachment buckle surgery there were two
      cases of scleral perforation. In one case, scleral perforation occurred during
      buckle installation and in the other case during placement of a cerclage. The
      rate of scleral perforation was 2.5 % per patient and per eye in this group. In
      the group receiving eye muscle surgery no scleral perforations occurred.
      CONCLUSION: The number of scleral perforations was higher in retinal detachment
      buckle surgery than in eye muscle surgery, with all procedures having been
      performed by the same surgeon.

PMID- 16950746
TI  - About the relation between the convergence of the visual axes and the
      accommodative status of the eyes.

PMID- 16950747
TI  - Physiologic hyperphoria and the dorsal light reflex in humans with normal
      binocular vision.

PMID- 16950750
TI  - The use of insulin sensitising agents in ovulation induction in women with
      polycystic ovary syndrome.
AB  - Insulin resistance is an important "upstream" driver for reproductive and
      metabolic abnormalities in women with Polycystic Ovary Syndrome (PCOS). This
      theoretical background is now supported by substantial evidence for treating
      women with PCOS with insulin sensitising agents such as metformin or the
      thiazolidinediones. Although the available data are based upon studies comprised
      of relatively small numbers of patients, powerful evidence of potential benefit
      is emerging. Data from controlled studies, which are usually short-term and of
      limited magnitude, indicate modest effects of insulin sensitizers on ovulation
      when applied as the only drug. However, potentially important benefits are
      achieved when such treatment is combined with other methods. These benefits
      include both increased fertility and decreased risks for ovarian hyperstimulation
      syndrome (OHSS). Furthermore, there may also be benefits in terms of alleviation
      of pregnancy complications. The available evidence supports consideration of the
      use of metformin from the earliest stages of treatment in women with PCOS.

PMID- 16950751
TI  - Thyroid nodules 2006: managing what has been known for over 50 years.

PMID- 16950752
TI  - Changes in prothrombin and activated partial thromboplastin time during
      replacement therapy with human recombinant growth hormone in growth hormone
      deficient adults.
AB  - BACKGROUND: In rodents, Growth Hormone (GH) has been shown to stimulate
      coagulation parameters, including Prothrombin Time (PT), activated Partial
      Thromboplastin Time (aPTT) and vitamin K dependent coagulation factors. However,
      there are no reports on the influence of GH replacement therapy on global
      coagulation tests in Growth Hormone Deficiency (GHD). OBJECTIVE: The aim of this
      study was to investigate the effects of GH administration on basic coagulation
      parameters: PT, aPTT and fibrinogen concentrations in adult GHD patients before
      and during one year of GH replacement. DESIGN: Twenty-one adult patients with
      severe GHD (mean age +/- SE: 38.6 +/- 2.8 years) were included in this hospital
      based, prospective, interventional study. All patients were treated with rhGH for
      12 months (GH dose: 0.4 mg/day for male and 0.6 mg/day for female patients). IGF
      1 concentrations were determined using RIA-INEP kits. Basic coagulation tests,
      i.e. aPTT and fibrinogen concentrations, were measured before and after 3, 6 and
      12 months of treatment with rhGH. Control values were obtained from fourteen
      "healthy" subjects matched by age, sex and body mass index (BMI). RESULTS: At
      baseline, we observed no significant differences in PT, aPTT and fibrinogen
      values between GHD and healthy subjects. IGF-1 concentrations increased
      significantly within 3 months of GH therapy (8.2 +/- 1.5 vs. 24.2 +/- 2.9 nmol/l,
      p <0.05) and remained stable thereafter. A significant increase in PT values,
      which was more pronounced in female subjects, was noted after 6 and 12 months of
      treatment with GH. aPTT values increased significantly after 12 months of
      treatment only in male patients (28.8 +/- 4.6 vs. 39.7 +/- 2.1 s.; p <0.05). No
      significant changes in fibrinogen concentrations were found during the study.
      CONCLUSIONS: Twelve months of GH replacement therapy led to a significant
      increase in PT and aPTT values in adult GHD patients, while fibrinogen
      concentrations did not change. Changes in PT were more pronounced in female GHD
      patients, while an increase in aPTT values was observed only in male patients
      with GHD. The clinical significance of these changes needs further evaluation.

PMID- 16950753
TI  - Plasma interleukin-6 levels, glutathione peroxidase and isoprostane in obese
      women before and after weight loss. Association with cardiovascular risk factors.
AB  - OBJECTIVE: To evaluate the levels of Interleukin-6 (IL-6), glutathione peroxidase
      and isoprostane in obese women and their association with markers of
      cardiovascular risk factors before and after weight loss. DESIGN: 36 healthy
      obese women of reproductive age (group A: age (mean+/-SD) 35.4+/-9.2 years, Body
      Mass Index (BMI) 38.5+/-7 kg/m2) and 30 healthy, normal weight women (group B:
      age mean+/-SD 34.9+/-7.4 y., BMI 24+/-1.1 kg/m2) were included in the study.
      Glucose tolerance was normal in all participating women. Il-6, glutathione
      peroxidase and isoprostane, C-Reactive Protein (CRP), insulin, fasting plasma
      glucose, HOMA-IR as well as the lipid profile were evaluated. Body weight, BMI,
      Waist to Hip ratio (W/H) ratio, Waist Circumference (WC), %free fat mass and the
      %fat mass were also measured. A hypo-caloric diet was prescribed for the obese
      women and all participants were re-examined after six months. RESULTS: In obese
      women after weight loss, anthropometric obesity markers (BMI, W/H ratio), %fat,
      lipid profile, insulin levels and inflammation indices such as IL-6 and CRP, the
      oxidative stress index isoprostane, as well as glutathione peroxidase were
      significantly ameliorated. The levels of serum glutathione peroxidase activity
      were negatively correlated with IL-6 levels and were significantly increased
      after weight reduction. In obese women there was an association between IL-6
      levels and the values of %fat, %free fat mass, insulin and HOMA-IR before and
      after weight loss. CONCLUSIONS: Weight loss is related to reduction of oxidative
      stress and inflammation; this beneficial effect could possibly be translated into
      reduction of cardiovascular risk in obese individuals.

PMID- 16950754
TI  - R831X mutation of the androgen receptor gene in an adolescent with complete
      androgen insensitivity syndrome and bilateral testicular hamartomata.
AB  - An 18-year old, phenotypically female individual was examined for primary
      amenorrhea. Three months before her referral, the patient underwent surgery and a
      pelvic mass was removed. The physical examination revealed normal female external
      genitalia, normal breast development, sparse pubic hair and absence of axillary
      hair. The gynecological examination revealed a short blind vagina pouch and
      absence of cervix and uterus. Serum testosterone and dihydrotestosterone levels
      were very high. Karyotype was that of a normal male (46,XY). The transabdominal
      ultrasound, computed tomography (CT) and Magnetic resonance imaging (MRI) showed
      absence of uterus and fallopian tubes and revealed testis-like gonads located at
      the internal opening of the inguinal canal bilaterally. Bilateral gonadectomy was
      subsequently performed. The pathology report was that of "hamartomatous testes"
      and associated paratesticular leiomyoma. The clinical, laboratory, imaging,
      genetic and histological findings confirmed the diagnosis of complete androgen
      insensitivity syndrome. DNA analysis revealed a R831X mutation in exon 7 of the
      androgen receptor gene. A Sertoli-cell dynamic test showed elevated basal serum
      inhibin-B and anti-Mullerian hormone levels without further rise following FSH
      stimulation. The patient was started on hormone replacement therapy with
      conjugated estrogens. Complete androgen insensitivity syndrome must be considered
      in any case of primary amenorrhea. Gonadectomy must be planned to eliminate the
      risk of gonadal malignancy.

PMID- 16950755
TI  - A boy with McCune-Albright syndrome associated with GH secreting pituitary
      microadenoma. Clinical findings and response to treatment.
AB  - The McCune-Albright Syndrome (MAS) is a sporadic rare disease first described in
      1936 by McCune and separately by Albright. MAS is characterized by a triad of
      physical signs: cafe-au-lait spots, polyostotic fibrous dysplasia and autonomous
      endocrine hyperfunction. MAS is predominantly observed in girls and is rarely
      reported in males. We report the case of a 9-year old boy with gonadotropin
      independent precocious puberty, cafe-au-lait spots, polyostotic fibrous dysplasia
      and growth hormone hypersecretion.

PMID- 16950756
TI  - Calciphylaxis: a complication of end-stage renal disease improved by
      parathyroidectomy.
AB  - A 43-year old Caucasian male with end-stage renal disease presented with painful
      skin lesions and high calcium phosphate product that did not respond to medical
      treatment. Skin biopsy confirmed the diagnosis of calciphylaxis. Urgent
      parathyroidectomy was performed and resulted in decrease in the calcium phosphate
      product and improvement of his symptoms and signs.

PMID- 16950757
TI  - Hermaphroditism in Greek and Roman antiquity.
AB  - Since antiquity hermaphrodites have fascinated the mind and excited the
      imagination. In this paper, such subjects are discussed as legends about the
      nativity of Hermaphroditus, son of Hermes and Aphrodite, the social status of
      these bisexual beings, and their fate in Greek-Roman antiquity.

PMID- 16950758
TI  - Diversifying selection drives the evolution of the type III secretion system
      pilus of Pseudomonas syringae.
AB  - The plant pathogenic bacterium Pseudomonas syringae uses a type III secretion
      system to inject virulence proteins directly into the cytoplasm of its hosts. The
      P. syringae type III secretion apparatus is encoded, in part, by the HrpZ operon,
      which carries the hrpA gene encoding the pilin subunit of the pilus, various
      components of the structural apparatus, and the HrpZ harpin protein that is
      believed to produce pores in the host cell membrane. The pilus of the type III
      system comes into direct contact with the host cell and is, therefore, a likely
      target of the host's pathogen surveillance systems. We sequenced and analyzed 22
      HrpZ operons from P. syringae strains spanning the diversity of the species.
      Selection analyses, including K(a)/K(s) tests and Tajima's D, revealed strong
      diversifying selection acting on the hrpA gene. This form of selection enables
      pathogens to maintain genetic diversity within their populations and is often
      driven by selection imposed by host defense systems. The HrpZ operon also
      revealed a single significant recombination event that dramatically changed the
      evolutionary relationships among P. syringae strains from 2 quite distinct
      phylogroups. This recombination event appears to have introduced genetic
      diversity into a clade of strains that may now be undergoing positive selection.
      The identification of diversifying selection acting on the Hrp pilus across the
      whole population sample and positive selection within one P. syringae lineage
      supports a trench warfare coevolutionary model between P. syringae and its plant
      hosts.

PMID- 16950759
TI  - The unusual adaptive expansion of pancreatic ribonuclease gene in carnivora.
AB  - Pancreatic ribonuclease (RNASE1) is a digestive enzyme that has been recognized
      to be one of the most attractive model systems for molecular evolutionary
      studies. The contribution of RNASE1 gene duplication to the functional adaptation
      of digestive physiology in foregut-fermenting herbivores, mostly in ruminants,
      has been well documented. However, no one has ever done a comprehensive study on
      the carnivores, which are sister to the artiodactyls. Here, we sequenced this
      gene from 15 species of the superfamily Caniformia in order Carnivora, which all
      have a relatively simple digestive system and lack the microbial digestion in
      rumen or cecum typical of most herbivores. In contrast to our initial expectation
      that only a single RNASE1 gene is present in these carnivores, we observed a
      "birth (gene duplication)-and-death (gene deactivation)" process for the
      evolution of RNASE1 genes in all 3 species of Mustelidae family examined here,
      adding the growing diversity of RNASE1 gene family evolution. In addition, bursts
      of positive selection have been shown to contribute the enigmatic diversification
      of these RNASE1 genes in Mustelidae. The finding of the adaptive expansion of
      RNASE1 in animals without foregut fermentation provides another opportunity for
      further studies of the structure, function, and evolution of this gene, raising
      the possibility that new tissue specificity or other functions of RNASE1 genes
      might have developed in these species.

PMID- 16950760
TI  - The functional lumen imaging probe (FLIP) for evaluation of the esophagogastric
      junction.
AB  - There is a need for new methods to study the dynamics of the esophagogastric
      junction (EGJ). The aims were to verify the efficacy and usefulness of a
      "functional lumen imaging probe" (FLIP) for the evaluation of the EGJ. Eight
      healthy volunteers (6 men), median age 26 (21-35) yr, and two achalasia patients
      underwent the FLIP procedure. The EGJ was located by manometry. The FLIP measured
      eight cross-sectional areas (CSAs) 4 mm apart together with the pressure inside a
      saline-filled cylindrical bag. The data showed the geometric profile of the EGJ
      reconstructed in a video animation of its dynamic activity. A plot of curve
      fitted data for the smallest CSA vs. pressure after balloon distension indicated
      that the pressure increased from 18 cmH2O at a CSA of 38 mm2 to a pressure of 37
      cmH2O at a CSA of 230 mm2 for the healthy controls. In one achalasia patient
      (unsuccessfully treated with dilations), the CSA never rose above the minimal
      measurable value despite the pressure increasing to 50 cmH2O. In another
      achalasia patient (successfully treated with dilations), the pressure only
      reached 15 cmH2O despite opening to a CSA of 250 mm2. In conclusion, FLIP
      represents the first dynamic technique to profile the function and anatomy of the
      EGJ. The method can be used practically to evaluate difficult cases of EGJ
      dysfunction and may provide a role in evaluating patients before and after
      therapies for diseases affecting the EGJ such as achalasia and gastroesophageal
      reflux disease.

PMID- 16950761
TI  - Hepatocyte NF-kappaB activation is hepatoprotective during ischemia-reperfusion
      injury and is augmented by ischemic hypothermia.
AB  - The present study examined the role of hepatocyte NF-kappaB activation during
      ischemia-reperfusion injury. Second, we evaluated the effects of ischemic
      hypothermia on NF-kappaB activation and liver injury. C57BL/6 mice underwent 90
      min of partial hepatic ischemia and up to 8 h of reperfusion. Body temperature
      was regulated during the ischemic period between 35 and 37 degrees C, 33 and 35
      degrees C, 29 and 33 degrees C or unregulated, where temperature fell to <29
      degrees C. Liver injury, as measured by serum alanine aminotransferase as well as
      liver histopathology, was inversely proportional to regulated body temperature,
      with the unregulated group (<29 degrees C) being highly protected and the
      normothermic group (35-37 degrees C) displaying the greatest injury.
      Inflammation, as measured by production of TNF-alpha and liver recruitment of
      neutrophils, was greatest in the normothermic groups and lowest in the ischemic
      hypothermia groups. Interestingly, hepatocyte NF-kappaB activation was highest in
      the hypothermic group and least in the normothermic group. Paradoxically,
      degradation of IkappaB proteins, IkappaB-alpha and IkappaB-beta, was greatest in
      the normothermic group, suggesting an alternate NF-kappaB regulatory mechanism
      during ischemia-reperfusion injury. Subsequently, we found that NF-kappaB p65
      protein was increasingly degraded in normothermic versus hypothermic groups, and
      this degradation was specific for hepatocytes and was associated with decreased
      expression of the peptidyl-prolyl isomerase Pin1. The data suggest that NF-kappaB
      activation in hepatocytes is a protective response during ischemia-reperfusion
      and can be augmented by ischemic hypothermia. Furthermore, it appears that Pin1
      promotes NF-kappaB p65 protein stability such that decreased expression of Pin1
      during ischemia-reperfusion results in p65 degradation, reduced nuclear
      translocation of NF-kappaB, and enhanced hepatocellular injury.

PMID- 16950762
TI  - Rectal sensorimotor dysfunction in women with fecal incontinence.
AB  - The rate and pattern of rectal distension affect rectal distensibility,
      perception, and anal relaxation in health. Because rectal urgency is a prominent
      symptom in fecal incontinence (FI), we assessed rectal distensibility,
      contractions, perception, and anal pressures during rectal distention in 21
      healthy, asymptomatic women (age 61 +/- 2 yr, mean +/- SE) and 51 women with FI
      (60 +/- 2 yr). Rectal staircases (0-32 mmHg, 4-mm steps) and ramp distensions [0
      200 ml at 25, 50, and 100 ml/min with a phase of sustained distension (SD),
      lasting 1 min, between inflation and deflation]. The rectum was stiffer during
      rapid than slow ramp distention. This effect was more prominent at a lower volume
      (50 ml) and was also more pronounced in older subjects and in FI. A rectal
      contractile response was observed not only during inflation but also during SD
      and during deflation. During inflation, this contractile response was rate
      dependent in controls but not in FI. During staircase but not ramp distentions,
      the threshold for the desire to defecate was lower in FI. During ramp
      distentions, the duration of perception was significantly longer in FI. The rate
      of distention did not affect rectal perception (i.e., sensory thresholds or
      duration of perception) during ramp distentions. Baseline anal pressures and the
      magnitude of anal relaxation during rectal distention were also reduced in FI. In
      addition to reduced rectal capacity and compliance, women with FI had an
      exaggerated rate-dependent reduction in rectal distensibility, lower sensory
      thresholds, and more prolonged perception, indicative of rectoanal dysfunctions.

PMID- 16950763
TI  - Role of CCN2/CTGF in the proliferation of Mastomys enterochromaffin-like cells
      and gastric carcinoid development.
AB  - Mastomys enterochromaffin-like (ECL) cell proliferation is initially gastrin
      driven, but once neoplasia develops, cells become gastrin autonomous. We
      hypothesized that CCN2 (CTGF), a mitogenic growth factor, may regulate ECL cell
      proliferation. A Mastomys GeneChip database was examined (dCHIP) to identify CCN2
      expression levels. CCN2 in normal and tumor ECL cell preparations obtained using
      FACS (100 nM acridine orange) was examined by real-time PCR. CCN2 protein was
      identified in mucosal and ECL cell preparations by immunohistochemistry. Short
      term cultured cells were stimulated with either CCN2 or CCN2 + EGF, and
      proliferation was measured (MTT assay). The ERK1/2 inhibitor PD-98059 (0.1-100
      microM) was assessed in terms of CCN2 (1 ng/ml)-mediated proliferation and ERK1/2
      phosphorylation. CCN2 transcript and protein was then examined in clinical
      gastric carcinoids. The ccn2 transcript was upregulated in tumor samples compared
      with the normal mucosa (+2.36-fold, P < 0.01). PCR demonstrated that ccn2 was not
      expressed in FACS-prepared (>98% pure) normal ECL cells but was elevated in tumor
      ECL cell fractions (41.3 +/- 10.7-fold). Immunostaining of the Mastomys gastric
      mucosa and FACS preparations confirmed that CCN2 protein was present in ECL
      tumors but not in normal ECL cells. Neither CCN2 nor CCN2 + EGF stimulated normal
      ECL cell proliferation. CCN2 stimulated tumor proliferation (EC50 approximately
      0.01 ng/ml); EGF significantly augmented (P < 0.01) CCN2-induced tumor cell
      proliferation (EC50 = 20 pg/ml). PD-98059 inhibited CCN2-induced proliferation (
      12 +/- 3%, P < 0.05) and ERK1/2 phosphorylation (-34 +/- 5%, P < 0.05) in tumor
      cells. In clinical samples, both CCN2 transcript and protein were elevated in
      gastrin-autonomous carcinoids (P < 0.02) compared with the normal mucosa. In
      conclusion, CCN2 may be a proliferative regulator of Mastomys ECL neoplastic
      proliferation once these cells become autonomous of gastrin regulation.
      Identification of CCN2 in gastric carcinoid tissue may be useful both as an
      indicator of ECL cell transformation and may define gastrin autonomy, a criteria
      of gastric carcinoid malignancy.

PMID- 16950764
TI  - Coordinate transcriptional repression of liver fatty acid-binding protein and
      microsomal triglyceride transfer protein blocks hepatic very low density
      lipoprotein secretion without hepatosteatosis.
AB  - Unlike the livers of humans and mice, and most hepatoma cells, which accumulate
      triglycerides when treated with microsomal triglyceride transfer protein (MTP)
      inhibitors, L35 rat hepatoma cells do not express MTP and cannot secrete very low
      density lipoprotein (VLDL), yet they do not accumulate triglyceride. In these
      studies we show that transcriptional co-repression of the two lipid transfer
      proteins, liver fatty acid-binding protein (L-FABP) and MTP, which cooperatively
      shunt fatty acids into de novo synthesized glycerolipids and the transfer of
      lipids into VLDL, respectively, act together to maintain hepatic lipid
      homeostasis. FAO rat hepatoma cells express L-FABP and MTP and demonstrate the
      ability to assemble and secrete VLDL. In contrast, L35 cells, derived as a single
      cell clone from FAO cells, do not express L-FABP or MTP nor do they assemble and
      secrete VLDL. We used these hepatoma cells to elucidate how a conserved DR1
      promoter element present in the promoters of L-FABP and MTP affects
      transcription, expression, and VLDL production. In FAO cells, the DR1 elements of
      both L-FABP and MTP promoters are occupied by peroxisome proliferator-activated
      receptor alpha-retinoid X receptor alpha (RXRalpha), with which PGC-1beta
      activates transcription. In contrast, in L35 cells the DR1 elements of both L
      FABP and MTP promoters are occupied by chicken ovalbumin upstream promoter
      transcription factor II, and transcription is diminished. The combined findings
      indicate that peroxisome proliferator-activated receptor alpha-RXRalpha and PGC
      1beta coordinately up-regulate L-FABP and MTP expression, by competing with
      chicken ovalbumin upstream promoter transcription factor II for the DR1 sites in
      the proximal promoters of each gene. Additional studies show that ablation of L
      FABP prevents hepatic steatosis caused by treating mice with an MTP inhibitor.
      Our findings show that reducing both L-FABP and MTP is an effective means to
      reduce VLDL secretion without causing hepatic steatosis.

PMID- 16950765
TI  - Temporal regulation of enhancer function in intestinal epithelium: a role for
      Onecut factors.
AB  - An intestine-specific gene regulatory region was previously identified near the
      second exon of the human adenosine deaminase (ADA) gene. In mammalian intestine,
      ADA is expressed at high levels only along the villi of the duodenal epithelium,
      principally if not exclusively in enterocytes. Within the ADA intestinal
      regulatory region, a potent duodenum-specific enhancer was identified that
      controls this pattern of expression. This enhancer has been shown to rely on PDX
      1, GATA factors, and Cdx factors for its function. Upstream of the enhancer, a
      separate temporal regulatory region was identified that has no independent
      enhancer capability but controls the timing of enhancer activation. DNase I
      footprinting and electrophoretic mobility shift assays were used to begin to
      characterize temporal region function at the molecular level. In this manner,
      binding sites for the Onecut (OC) family of factors, YY1, and NFI family members
      were identified. Identification of the OC site was especially interesting,
      because almost nothing is known about the function of OC factors in intestine. In
      transgenic mice, mutation of the OC site to ablate binding resulted in a delay of
      2-3 weeks in enhancer activation in the developing postnatal intestine, a result
      very similar to that observed previously when the entire temporal region was
      deleted. In mammals, the OC family is comprised of OC-1/HNF-6, OC-2, and OC-3. An
      examination of intestinal expression patterns showed that all three OC factors
      are expressed at detectable levels in adult mouse duodenum, with OC-2
      predominant. In postnatal day 2 mice only OC-2 and OC-3 were detected in
      intestine, with OC-2 again predominant.

PMID- 16950766
TI  - Mechanisms by which Bloom protein can disrupt recombination intermediates of
      Okazaki fragment maturation.
AB  - Bloom syndrome is a familial genetic disorder associated with sunlight
      sensitivity and a high predisposition to cancers. The mutated gene, Bloom protein
      (BLM), encodes a DNA helicase that functions in genome maintenance via roles in
      recombination repair and resolution of recombination structures. We designed
      substrates representing illegitimate recombination intermediates formed when a
      displaced DNA flap generated during maturation of Okazaki fragments escapes
      cleavage by flap endonuclease-1 and anneals to a complementary ectopic DNA site.
      Results show that displaced, replication protein A (RPA)-coated flaps could
      readily bind and ligate at the complementary site to initiate recombination. RPA
      also displayed a strand-annealing activity that hastens the rate of recombination
      intermediate formation. BLM helicase activity could directly disrupt annealing at
      the ectopic site and promote flap endonuclease-1 cleavage. Additionally, BLM has
      its own strand-annealing and strand-exchange activities. RPA inhibited the BLM
      strand-annealing activity, thereby promoting helicase activity and complex
      dissolution. BLM strand exchange could readily dissociate invading flaps, e.g. in
      a D-loop, if the exchange step did not involve annealing of RPA-coated strands.
      Use of ATP to activate the helicase function did not aid flap displacement by
      exchange, suggesting that this is a helicase-independent mechanism of complex
      dissociation. When RPA could bind, it displayed its own strand-exchange activity.
      We interpret these results to explain how BLM is well equipped to deal with
      alternative recombination intermediate structures.

PMID- 16950767
TI  - Lipopolysaccharide-induced cyclooxygenase-2 expression in human U937 macrophages
      is phosphatidic acid phosphohydrolase-1-dependent.
AB  - Cyclooxygenase (COX) has two isoforms, COX-1 and -2, which catalyze the key step
      in the conversion of cellular arachidonic acid into prostaglandins. In recent
      years, interest in COX-2 has significantly increased since it has been a target
      for the development of specific non-steroidal anti-inflammatory drugs. We report
      that COX-2 expression is up-regulated in phorbol ester (phorbol myristate
      acetate, PMA)-differentiated human U937 macrophage-like cells stimulated with
      lipopolysaccharide (LPS), whereas COX-1 is not up-regulated. We show that the LPS
      induced up-regulation of COX-2 depends on the activity of the Mg(+2)-dependent
      phosphatidic acid phosphohydrolase 1 (PAP-1). Inhibition of PAP-1 by bromoenol
      lactone, propranolol, or ethanol resulted in a decrease in LPS-induced COX-2 mRNA
      transcript production, COX-2 protein expression, and prostaglandin E(2) release
      from U937 macrophages. To ensure that these results did not arise because of PMA
      treatment of the U937 cells, similar experiments were conducted with the P388D(1)
      cell line, which does not require PMA differentiation. LPS increased the levels
      of endogenous cellular diacylglycerol (DAG) within 2 min of stimulation. This
      increase was observed to be sensitive to the PAP-1 inhibitors. Furthermore,
      phosphatidic acid phosphohydrolase activity assays showed that the bromoenol
      lactone-sensitive PAP-1 activity was translocated from the cytosolic fraction to
      the membrane fraction within 2 min of LPS exposure. Finally, DAG add-back
      experiments demonstrate that LPS-induced COX-2 expression is enhanced by the
      addition of exogenous DAG.

PMID- 16950768
TI  - A bifunctional Delta12,Delta15-desaturase from Acanthamoeba castellanii directs
      the synthesis of highly unusual n-1 series unsaturated fatty acids.
AB  - The free-living soil protozoon Acanthamoeba castellanii synthesizes a range of
      polyunsaturated fatty acids, the balance of which can be altered by environmental
      changes. We have isolated and functionally characterized in yeast a microsomal
      desaturase from A. castellanii, which catalyzes the sequential conversion of
      C(16) and C(18) Delta9-monounsaturated fatty acids to di- and tri-unsaturated
      forms. In the case of C(16) substrates, this bifunctional A. castellanii
      Delta12,Delta15-desaturase generated a highly unusual fatty acid,
      hexadecatrienoic acid (16:3Delta(9,12,15)(n-1)). The identification of a
      desaturase, which can catalyze the insertion of a double bond between the
      terminal two carbons of a fatty acid represents a new addition to desaturase
      functionality and plasticity. We have also co-expressed in yeast the A.
      castellanii bifunctional Delta12,Delta15-desaturase with a microsomal Delta6
      desaturase, resulting in the synthesis of the highly unsaturated C(16) fatty acid
      hexadecatetraenoic acid (16:4Delta(6,9,12,15)(n-1)), previously only reported in
      marine microorganisms. Our work therefore demonstrates the feasibility of the
      heterologous synthesis of polyunsaturated fatty acids of the n-1 series. The
      presence of a bifunctional Delta12,Delta15-desaturase in A. castellanii is also
      considered with reference to the evolution of desaturases and the lineage of this
      protist.

PMID- 16950769
TI  - The EphB4 receptor-tyrosine kinase promotes the migration of melanoma cells
      through Rho-mediated actin cytoskeleton reorganization.
AB  - Several studies have reported the up-regulation of EphB receptor-tyrosine kinases
      and ephrin-B ligands in a variety of tumors, suggesting a functional relation
      between EphB/ephrin-B signaling and tumor progression. The ability of the EphB
      receptors to regulate cell migration and promote angiogenesis likely contributes
      to tumor progression and metastasis. Here we show that EphB receptors, and
      especially EphB4, regulate the migration of murine melanoma cells. Highly
      malignant melanoma cells express the highest levels of EphB4 receptor and migrate
      faster than less malignant melanoma cells. Furthermore, inhibition of EphB
      receptor forward signaling by overexpression of a form of EphB4 lacking the
      cytoplasmic portion or by treatment with competitively acting soluble EphB2-Fc
      results in slower melanoma cell migration. In contrast, overexpression of active
      EphB4 significantly enhances cell migration. The effects of EphB4 receptor on
      cell migration and cell morphology require its kinase activity because the
      inhibition of EphB4 kinase activity by overexpression of kinase dead EphB4
      inhibits cell migration and affects the organization of actin cytoskeleton.
      Activation of EphB4 receptor with its ligand ephrin-B2-Fc enhances the migratory
      ability of melanoma cells and increases RhoA activity, whereas inhibiting EphB
      receptor forward signaling decreases RhoA activity. Moreover, expression of
      dominant negative RhoA blocks the effects of active EphB4 on cell migration and
      actin organization. These data suggest that EphB4 forward signaling contributes
      to the high migratory ability of invasive melanoma cells by influencing RhoA
      mediated actin cytoskeleton reorganization.

PMID- 16950770
TI  - Akt2 regulates cardiac metabolism and cardiomyocyte survival.
AB  - The Akt family of serine-threonine kinases participates in diverse cellular
      processes, including the promotion of cell survival, glucose metabolism, and
      cellular protein synthesis. All three known Akt family members, Akt1, Akt2 and
      Akt3, are expressed in the myocardium, although Akt1 and Akt2 are most abundant.
      Previous studies demonstrated that Akt1 and Akt3 overexpression results in
      enhanced myocardial size and function. Yet, little is known about the role of
      Akt2 in modulating cardiac metabolism, survival, and growth. Here, we utilize
      murine models with targeted disruption of the akt2 or the akt1 genes to
      demonstrate that Akt2, but not Akt1, is required for insulin-stimulated 2
      [(3)H]deoxyglucose uptake and metabolism. In contrast, akt2(-/-) mice displayed
      normal cardiac growth responses to provocative stimulation, including ligand
      stimulation of cultured cardiomyocytes, pressure overload by transverse aortic
      constriction, and myocardial infarction. However, akt2(-/-) mice were found to be
      sensitized to cardiomyocyte apoptosis in response to ischemic injury, and
      apoptosis was significantly increased in the peri-infarct zone of akt2(-/-)
      hearts 7 days after occlusion of the left coronary artery. These results
      implicate Akt2 in the regulation of cardiomyocyte metabolism and survival.

PMID- 16950771
TI  - Bovine complex I is a complex of 45 different subunits.
AB  - Mammalian mitochondrial complex I is a multisubunit membrane-bound assembly with
      a molecular mass approaching 1 MDa. By comprehensive analyses of the bovine
      complex and its constituent subcomplexes, 45 different subunits have been
      characterized previously. The presence of a 46th subunit was suspected from the
      consistent detection of a molecular mass of 10,566 by electrospray ionization
      mass spectrometry of subunits fractionated by reverse-phase high pressure liquid
      chromatography. The component was found associated with both the intact complex
      and subcomplex Ibeta, which represents most of the membrane arm of the complex,
      and it could not be resolved chromatographically from subunit SGDH (the subunit
      of bovine complex I with the N-terminal sequence Ser-Gly-Asp-His). It has now
      been characterized by tandem mass spectrometry of intact protein ions and shown
      to be a C-terminal fragment of subunit SGDH arising from a specific peptide bond
      cleavage between Ile-55 and Pro-56 during the electrospray ionization process.
      Thus, the subunit composition of bovine complex I has been established. It is a
      complex of 45 different proteins plus non-covalently bound FMN and eight iron
      sulfur clusters.

PMID- 16950773
TI  - Gib2, a novel Gbeta-like/RACK1 homolog, functions as a Gbeta subunit in cAMP
      signaling and is essential in Cryptococcus neoformans.
AB  - Canonical G proteins are heterotrimeric, consisting of alpha, beta, and gamma
      subunits. Despite multiple Galpha subunits functioning in fungi, only a single
      Gbeta subunit per species has been identified, suggesting that non-conventional G
      protein signaling exists in this diverse group of eukaryotic organisms. Using the
      Galpha subunit Gpa1 that functions in cAMP signaling as bait in a two-hybrid
      screen, we have identified a novel Gbeta-like/RACK1 protein homolog, Gib2, from
      the human pathogenic fungus Cryptococcus neoformans. Gib2 contains a seven WD-40
      repeat motif and is predicted to form a seven-bladed beta propeller structure
      characteristic of beta transducins. Gib2 is also shown to interact, respectively,
      with two Ggamma subunit homologs, Gpg1 and Gpg2, similar to the conventional
      Gbeta subunit Gpb1. In contrast to Gpb1 whose overexpression promotes mating
      response, overproduction of Gib2 suppresses defects of gpa1 mutation in both
      melanization and capsule formation, the phenotypes regulated by cAMP signaling
      and associated with virulence. Furthermore, depletion of Gib2 by antisense
      suppression results in a severe growth defect, suggesting that Gib2 is essential.
      Finally, Gib2 is shown to also physically interact with a downstream target of
      Gpa1-cAMP signaling, Smg1, and the protein kinase C homolog Pkc1, indicating that
      Gib2 is also a multifunctional RACK1-like protein.

PMID- 16950772
TI  - CTIP2 associates with the NuRD complex on the promoter of p57KIP2, a newly
      identified CTIP2 target gene.
AB  - Chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting
      protein 2 (CTIP2), also known as Bcl11b, is a transcriptional repressor that
      functions by direct, sequence-specific DNA binding activity or by recruitment to
      the promoter template by interaction with COUP-TF family members. CTIP2 is
      essential for both T cell development and axonal projections of corticospinal
      motor neurons in the central nervous system. However, little is known regarding
      the molecular mechanism(s) by which CTIP2 contributes to either process. CTIP2
      complexes that were isolated from SK-N-MC neuroblastoma cells were found to
      harbor substantial histone deacetylase activity, which was likely conferred by
      the nucleosome remodeling and deacetylation (NuRD) complex. CTIP2 was found to
      associate with the NuRD complex through direct interaction with both RbAp46 and
      RbAp48, and components of the NuRD complex were found to be recruited to an
      artificial promoter template in a CTIP2-dependent manner in transfected cells.
      Finally, the NuRD complex and CTIP2 were found to co-occupy the promoter template
      of p57KIP2, a gene encoding a cyclin-dependent kinase inhibitor, and identified
      herein as a novel transcriptional target of CTIP2 in SK-N-MC cells. Therefore, it
      seems likely that the NuRD complex may be involved in transcriptional repression
      of CTIP2 target genes and contribute to the function(s) of CTIP2 within a
      neuronal context.

PMID- 16950774
TI  - Kinectin-dependent assembly of translation elongation factor-1 complex on
      endoplasmic reticulum regulates protein synthesis.
AB  - Kinectin is an integral membrane protein with many isoforms primarily found on
      the endoplasmic reticulum. It has been found to bind kinesin, Rho GTPase, and
      translation elongation factor-1delta. None of the existing models for the
      quaternary organization of the elongation factor-1 complex in higher eukaryotes
      involves kinectin. We have investigated here the assembly of the elongation
      factor-1 complex onto endoplasmic reticulum via kinectin using in vitro and in
      vivo assays. We established that the entire elongation factor-1 complex can be
      anchored to endoplasmic reticulum via kinectin, and the interacting partners are
      as follows. Kinectin binds EF-1delta, which in turn binds EF-1gamma but not EF
      1beta; EF-1gamma binds EF-1delta and EF-1beta but not kinectin. In vivo splice
      blocking of the kinectin exons 36 and 37 produced kinectin lacking the EF-1delta
      binding domain, which disrupted the membrane localization of EF-1delta, EF
      1gamma, and EF-1beta on endoplasmic reticulum, similar to the disruptions seen
      with the overexpression of kinectin fragments containing the EF-1delta binding
      domain. The disruptions of the EF-1delta/kinectin interaction inhibited
      expression of membrane proteins but enhanced synthesis of cytosolic proteins in
      vivo. These findings suggest that anchoring the elongation factor-1 complex onto
      endoplasmic reticulum via EF-1delta/kinectin interaction is important for
      regulating protein synthesis in eukaryotic cells.

PMID- 16950775
TI  - The quinone binding site in Escherichia coli succinate dehydrogenase is required
      for electron transfer to the heme b.
AB  - We have examined the role of the quinone-binding (Q(P)) site of Escherichia coli
      succinate:ubiquinone oxidoreductase (succinate dehydrogenase) in heme reduction
      and reoxidation during enzyme turnover. The SdhCDAB electron transfer pathway
      leads from a cytosolically localized flavin adenine dinucleotide cofactor to a
      Q(P) site located within the membrane-intrinsic domain of the enzyme. The Q(P)
      site is sandwiched between the [3Fe-4S] cluster of the SdhB subunit and the heme
      b(556) that is coordinated by His residues from the SdhC and SdhD subunits. The
      intercenter distances between the cluster, heme, and Q(P) site are all within the
      theoretical 14 A limit proposed for kinetically competent intercenter electron
      transfer. Using EPR spectroscopy, we have demonstrated that the Q(P) site of
      SdhCDAB stabilized a ubisemiquinone radical intermediate during enzyme turnover.
      Potentiometric titrations indicate that this species has an E(m,8) of
      approximately 60 mV and a stability constant (K(STAB)) of approximately 1.0.
      Mutants of the following conserved Q(P) site residues, SdhC-S27, SdhC-R31, and
      SdhD-D82, have severe consequences on enzyme function. Mutation of the conserved
      SdhD-Y83 suggested to hydrogen bond to the ubiquinone cofactor had a less severe
      but still significant effect on function. In addition to loss of overall
      catalysis, these mutants also affect the rate of succinate-dependent heme
      reduction, indicating that the Q(P) site is an essential stepping stone on the
      electron transfer pathway from the [3Fe-4S] cluster to the heme. Furthermore, the
      mutations result in the elimination of EPR-visible ubisemiquinone during
      potentiometric titrations. Overall, these results demonstrate the importance of a
      functional, semiquinone-stabilizing Q(P) site for the observation of rapid
      succinate-dependent heme reduction.

PMID- 16950776
TI  - The anti-angiogenic activity of rPAI-1(23) inhibits fibroblast growth factor-2
      functions.
AB  - Many angiogenesis inhibitors are breakdown products of endogenous extracellular
      matrix proteins. Plasmin and matrix metalloproteinase-3 generate breakdown
      products of matrix-bound plasminogen activator inhibitor-1 (PAI-1). We produced a
      truncated form of PAI-1, rPAI-1(23), that possesses significant anti-angiogenic
      activity and stimulates high levels of apoptosis in quiescent arterial
      endothelial cells. Quiescent endothelial cells are less susceptible to apoptosis
      than angiogenic endothelial cells. The present study was designed to determine
      the mechanism of the rPAI-1(23) effects in bovine aortic endothelial cells.
      Apoptosis was measured in annexin V and caspase 3 assays. Expression of death and
      survival signaling molecules were examined by Western blot and kinase activity.
      Fibroblast growth factor 2 (FGF2) functions were analyzed in angiogenesis assays.
      The early response to rPAI-1(23) was an increase in annexin V-positive cells and
      phosphorylated (p) JNK isoform expression followed by an increase in p-Akt and p
      c-Jun expression. Caspase 3 was activated at 4 h, whereas p-Akt was reduced to
      control levels. By 6 h of rPAI-1(23) treatment cell number was reduced by 35%,
      and p-c-Jun and p-JNK were degraded by proteasomes. Confocal microscopic images
      showed increased amounts of FGF2 in the extracellular matrix. However, rPAI-1(23)
      blocked FGF2 signaling through FGF receptor 1 and syndecan-4, inhibiting cell
      migration, tubulogenesis, and proliferation. Exogenous FGF2 stimulation could not
      reverse these effects. We conclude that rPAI-1(23) stimulation of apoptosis in
      BAEC triggers a cascade of death versus survival events that includes release of
      FGF2. The rPAI-1(23) anti-angiogenic activity inhibits FGF2 pro-angiogenic
      functions by blocking FGF2 signaling through FGF receptor 1 and syndecan-4 and
      downstream effectors p-Akt, p-JNK, and p-c-Jun.

PMID- 16950777
TI  - Translation elongation factor 2 anticodon mimicry domain mutants affect fidelity
      and diphtheria toxin resistance.
AB  - Eukaryotic elongation factor 2 (eEF2) mediates translocation in protein
      synthesis. The molecular mimicry model proposes that the tip of domain IV mimics
      the anticodon loop of tRNA. His-699 in this region is post-translationally
      modified to diphthamide, the target for Corynebacterium diphtheriae and
      Pseudomonas aeruginosa toxins. ADP-ribosylation by these toxins inhibits eEF2
      function causing cell death. Mutagenesis of the tip of domain IV was used to
      assess both functions. A H694A mutant strain was non-functional, whereas D696A,
      I698A, and H699N strains conferred conditional growth defects, sensitivity to
      translation inhibitors, and decreased total translation in vivo. These mutant
      strains and those lacking diphthamide modification enzymes showed increased -1
      frameshifting. The effects are not due to reduced protein levels, ribosome
      binding, or GTP hydrolysis. Functional eEF2 forms substituted in domain IV confer
      dominant diphtheria toxin resistance, which correlates with an in vivo effect on
      translation-linked phenotypes. These results provide a new mechanism in which the
      translational machinery maintains the accurate production of proteins,
      establishes a role for the diphthamide modification, and provides evidence of the
      ability to suppress the lethal effect of a toxin targeted to eEF2.

PMID- 16950778
TI  - The A-site finger in 23 S rRNA acts as a functional attenuator for translocation.
AB  - Helix 38 (H38) in 23 S rRNA, which is known as the "A-site finger (ASF)," is
      located in the intersubunit space of the ribosomal 50 S subunit and, together
      with protein S13 in the 30 S subunit, it forms bridge B1a. It is known that
      throughout the decoding process, ASF interacts directly with the A-site tRNA.
      Bridge B1a becomes disrupted by the ratchet-like rotation of the 30 S subunit
      relative to the 50 S subunit. This occurs in association with elongation factor G
      (EF-G)-catalyzed translocation. To further characterize the functional role(s) of
      ASF, variants of Escherichia coli ribosomes with a shortened ASF were
      constructed. The E. coli strain bearing such ASF-shortened ribosomes had a normal
      growth rate but enhanced +1 frameshift activity. ASF-shortened ribosomes showed
      normal subunit association but higher activity in poly(U)-dependent
      polyphenylalanine synthesis than the wild type (WT) ribosome at limited EF-G
      concentrations. In contrast, other ribosome variants with shortened bridge
      forming helices 34 and 68 showed weak subunit association and less efficient
      translational activity than the WT ribosome. Thus, the higher translational
      activity of ASF-shortened ribosomes is caused by the disruption of bridge B1a and
      is not due to weakened subunit association. Single round translocation analyses
      clearly demonstrated that the ASF-shortened ribosomes have higher translocation
      activity than the WT ribosome. These observations indicate that the intrinsic
      translocation activity of ribosomes is greater than that usually observed in the
      WT ribosome and that ASF is a functional attenuator for translocation that serves
      to maintain the reading frame.

PMID- 16950779
TI  - Identification and characterization of L-arabonate dehydratase, L-2-keto-3
      deoxyarabonate dehydratase, and L-arabinolactonase involved in an alternative
      pathway of L-arabinose metabolism. Novel evolutionary insight into sugar
      metabolism.
AB  - Azospirillum brasiliense possesses an alternative pathway of L-arabinose
      metabolism, different from the known bacterial and fungal pathways. In the
      preceding articles, we identified and characterized L-arabinose-1-dehydrogenase
      and alpha-ketoglutaric semialdehyde dehydrogenase, which catalyzes the first and
      final reaction steps in this pathway, respectively (Watanabe, S., Kodaki, T., and
      Makino, K. (2006) J. Biol. Chem. 281, 2612-2623 and Watanabe, S., Kodaki, T., and
      Makino, K. (2006) J. Biol. Chem. 281, 28876-28888). We here report the remaining
      three enzymes, L-arabonate dehydratase, L-2-keto-3-deoxyarabonate (L-KDA)
      dehydratase, and L-arabinolactonase. N-terminal amino acid sequences of L
      arabonate dehydratase and L-KDA dehydratase purified from A. brasiliense cells
      corresponded to those of AraC and AraD genes, which form a single transcriptional
      unit together with the L-arabinose-1-dehydrogenase gene. Furthermore, the L
      arabinolactonase gene (AraB) was also identified as a component of the gene
      cluster. Genetic characterization of the alternative L-arabinose pathway
      suggested a significant evolutional relationship with the known sugar metabolic
      pathways, including the Entner-Doudoroff (ED) pathway and the several modified
      versions. L-arabonate dehydratase belongs to the ILVD/EDD family and
      spectrophotometric and electron paramagnetic resonance analysis revealed it to
      contain a [4Fe-4S](2+) cluster. Site-directed mutagenesis identified three
      cysteine ligands essential for cluster coordination. L-KDA dehydratase was
      sequentially similar to DHDPS/NAL family proteins. D-2-Keto-3-deoxygluconate
      aldolase, a member of the DHDPS/NAL family, catalyzes the equivalent reaction to
      L-KDA aldolase involved in another alternative L-arabinose pathway, probably
      associating a unique evolutional event between the two alternative L-arabinose
      pathways by mutation(s) of a common ancestral enzyme. Site-directed mutagenesis
      revealed a unique catalytic amino acid residue in L-KDA dehydratase, which may be
      a candidate for such a natural mutation.

PMID- 16950780
TI  - Effects on ligand interaction and membrane translocation of the positively
      charged arginine residues situated along the C1 domain binding cleft in the
      atypical protein kinase C isoforms.
AB  - The C1 domain zinc finger structure is highly conserved among the protein kinase
      C (PKC) superfamily members. As the interaction site for the second messenger sn
      1,2-diacylglycerol (DAG) and for the phorbol esters, the C1 domain has been an
      important target for developing selective ligands for different PKC isoforms.
      However, the C1 domains of the atypical PKC members are DAG/phorbol ester
      insensitive. Compared with the DAG/phorbol ester-sensitive C1 domains, the rim of
      the binding cleft of the atypical PKC C1 domains possesses four additional
      positively charged arginine residues (at positions 7, 10, 11, and 20). In this
      study, we showed that mutation to arginines of the four corresponding sites in
      the C1b domain of PKCdelta abolished its high potency for phorbol 12,13
      dibutyrate in vitro, with only marginal remaining activity for phorbol 12
      myristate 13-acetate in vivo. We also demonstrated both in vitro and in vivo that
      the loss of potency to ligands was cumulative with the introduction of the
      arginine residues along the rim of the binding cavity rather than the consequence
      of loss of a single, specific residue. Computer modeling reveals that these
      arginine residues reduce access of ligands to the binding cleft and change the
      electrostatic profile of the C1 domain surface, whereas the basic structure of
      the binding cleft is still maintained. Finally, mutation of the four arginine
      residues of the atypical PKC C1 domains to the corresponding residues in the
      deltaC1b domain conferred response to phorbol ester. We speculate that the
      arginine residues of the C1 domain of atypical PKCs may provide an opportunity
      for the design of ligands selective for the atypical PKCs.

PMID- 16950781
TI  - Structural determinants for phosphatidic acid regulation of phospholipase C
      beta1.
AB  - Signaling from G protein-coupled receptors to phospholipase C-beta (PLC-beta) is
      regulated by coordinate interactions among multiple intracellular signaling
      molecules. Phosphatidic acid (PA), a signaling phospholipid, binds to and
      stimulates PLC-beta(1) through a mechanism that requires the PLC-beta(1) C
      terminal domain. PA also modulates Galpha(q) stimulation of PLC-beta(1). These
      data suggest that PA may have a key role in the regulation of PLC-beta(1)
      signaling in cells. The present studies addressed the structural requirements and
      the mechanism for PA regulation of PLC-beta(1). We used a combination of
      enzymatic assays, PA-binding assays, and circular dichroism spectroscopy to
      evaluate the interaction of PA with wild-type and mutant PLC-beta(1) proteins and
      with fragments of the Galpha(q) binding domain. The results identify a region
      that includes the alphaA helix and flexible loop of the Galpha(q)-binding domain
      as necessary for PA regulation. A mutant PLC-beta(1) with multiple
      alanine/glycine replacements for residues (944)LIKEHTTKYNEIQN(957) was markedly
      impaired in PA regulation. The high affinity and low affinity component of PA
      stimulation was reduced 70% and PA binding was reduced 45% in this mutant.
      Relative PLC stimulation by PA increased with PLC-beta(1) concentration in a
      manner suggesting cooperative binding to PA. Similar concentration dependence was
      observed in the PLC-beta(1) mutant. These data are consistent with a model for PA
      regulation of PLC-beta(1) that involves cooperative interactions, probably PLC
      homodimerization, that require the flexible loop region, as is consistent with
      the dimeric structure of the Galpha(q)-binding domain. PA regulation of PLC
      beta(1) requires unique residues that are not required for Galpha(q) stimulation
      or GTPase-activating protein activity.

PMID- 16950782
TI  - The CheYs of Rhodobacter sphaeroides.
AB  - The Escherichia coli two-component chemosensory pathway has been extensively
      studied, and its response regulator, CheY, has become a paradigm for response
      regulators. However, unlike E. coli, most chemotactic nonenteric bacteria have
      multiple CheY homologues. The roles and cellular localization of the CheYs in
      Rhodobacter sphaeroides were determined. Only two CheYs were required for
      chemotaxis, CheY(6) and either CheY(3) or CheY(4). These CheYs were partially
      localized to either of the two chemotaxis signaling clusters, with the remaining
      protein delocalized. Interestingly, mutation of the CheY(6) phosphorylatable
      aspartate to asparagine produced a stopped motor, caused by phosphorylation on
      alternative site Ser-83 by CheA. Extensive mutagenesis of E. coli CheY has
      identified a number of activating mutations, which have been extrapolated to
      other response regulators (D13K, Y106W, and I95V). Analogous mutations in R.
      sphaeroides CheYs did not cause activation. These results suggest that although
      the R. sphaeroides and E. coli CheYs are similar in that they require
      phosphorylation for activation, they may differ in both the nature of the
      phosphorylation-induced conformational change and their subsequent interactions
      with the flagellar motor. Caution should therefore be used when projecting from
      E. coli CheY onto novel response regulators.

PMID- 16950783
TI  - Modulation of the cellular cholesterol level affects shedding of the type XIII
      collagen ectodomain.
AB  - Type XIII collagen is a transmembrane protein that also exists as a soluble
      extracellular variant because of ectodomain shedding by proprotein convertases.
      Because ectodomain shedding in a growing number of transmembrane proteins has
      recently been shown to be dependent on their localization in cholesterol-enriched
      detergent-resistant membrane microdomains, this work aimed at analyzing this
      aspect of type XIII collagen ectodomain processing. In HT-1080 cells type XIII
      collagen and its cleaving proprotein convertase furin localized partially in
      detergent-resistant cholesterol-containing membrane microdomains. Disruption of
      these domains by lowering either the level or availability of the cellular
      cholesterol reduced ectodomain shedding, implying that, in such membrane domains
      correct cholesterol level is important for the regulation of type XIII collagen
      ectodomain processing. In addition, we show here that ectodomain of type XIII
      collagen is also shed intracellularly. HT-1080 cells released vesicles from the
      Golgi apparatus, which contained only the cleaved variant. Intracellular
      processing and the subsequent entry of the cleaved ectodomain into the vesicles
      was totally blocked by inhibition of the proprotein convertase function by cell
      permeable chloromethylketone, but not with cell-impermeable alpha1-antitrypsin
      Portland. This supports the hypothesis of type XIII collagen ectodomain also
      being cleaved intracellularly in the Golgi and suggests that the intracellular
      cleavage may act as a gating event in the vesicle-mediated ectodomain secretion.

PMID- 16950784
TI  - Modulation of GalT1 and SialT1 sub-Golgi localization by SialT2 expression
      reveals an organellar level of glycolipid synthesis control.
AB  - Ganglioside glycosyltransferases organize as multienzyme complexes that localize
      in different sub-Golgi compartments. Here we studied whether in CHO-K1 cells
      lacking CMP-NeuAc: GM3 sialyltransferase (SialT2), the sub-Golgi localization of
      UDP-Gal:glucosylceramide beta-1,4-galactosyltransferase (GalT1) and CMP
      NeuAc:lactosylceramide sialyltransferase (SialT1) complex is affected when
      SialT2, another member of this complex, is coexpressed. GalT1 and SialT1 sub
      Golgi localization was determined by studying the effect of brefeldin A (BFA) and
      monensin on the synthesis of glycolipids and on the sub-Golgi localization of
      GalT1(1-52)-CFP (cyan fluorescent protein) and SialT1(1-54)-YFP (yellow
      fluorescent protein) chimeras by single cell fluorescence microscopy and by
      isopycnic subfractionation. We found that BFA, and also monensin, impair the
      synthesis of glycolipids beyond GM3 ganglioside in wild type (WT) cells but
      beyond GlcCer in SialT2(+) cells. Although BFA redistributed GalT1-CFP and SialT1
      YFP to the endoplasmic reticulum in WT cells, a fraction of these chimeras
      remained associated with a distal Golgi compartment, enriched in trans Golgi
      network, and recycling endosome markers in SialT2(+) cells. In BFA-treated cells,
      the percentage of GalT1-CFP and SialT1-YFP associated with Golgi-like membrane
      fractions separated by isopycnic subfractionation was higher in SialT2(+) cells
      than in WT cells. These effects were reverted by knocking down the expression of
      SialT2 with specific siRNA. Results indicate that sub-Golgi localization of
      glycosyltransferase complexes may change according to the relative levels of the
      expression of participating enzymes and reveal a capacity of the organelle to
      adapt the topology of the glycolipid synthesis machinery to functional states of
      the cell.

PMID- 16950785
TI  - Canonical transient receptor potential channels promote cardiomyocyte hypertrophy
      through activation of calcineurin signaling.
AB  - The calcium/calmodulin-dependent phosphatase calcineurin plays a central role in
      the control of cardiomyocyte hypertrophy in response to pathological stimuli.
      Although calcineurin is present at high levels in normal heart, its activity
      appears to be unaffected by calcium during the course of a cardiac cycle. The
      mechanism(s) whereby calcineurin is selectively activated by calcium under
      pathological conditions has remained unclear. Here, we demonstrate that diverse
      signals for cardiac hypertrophy stimulate expression of canonical transient
      receptor potential (TRPC) channels. TRPC consists of a family of seven membrane
      spanning nonselective cation channels that have been implicated in the nonvoltage
      gated influx of calcium in response to G protein-coupled receptor signaling,
      receptor tyrosine kinase signaling, and depletion of internal calcium stores.
      TRPC3 expression is up-regulated in multiple rodent models of pathological
      cardiac hypertrophy, whereas TRPC5 expression is induced in failing human heart.
      We demonstrate that TRPC promotes cardiomyocyte hypertrophy through activation of
      calcineurin and its downstream effector, the nuclear factor of activated T cells
      transcription factor. These results define a novel role for TRPC channels in the
      control of cardiac growth, and suggest that a TRPC-derived pool of calcium
      contributes to selective activation of calcineurin in diseased heart.

PMID- 16950786
TI  - Isoaspartyl post-translational modification triggers anti-tumor T and B
      lymphocyte immunity.
AB  - A hallmark of the immune system is the ability to ignore self-antigens. In
      attempts to bypass normal immune tolerance, a post-translational protein
      modification was introduced into self-antigens to break T and B cell tolerance.
      We demonstrate that immune tolerance is bypassed by immunization with a post
      translationally modified melanoma antigen. In particular, the conversion of an
      aspartic acid to an isoaspartic acid within the melanoma antigen tyrosinase
      related protein (TRP)-2 peptide-(181-188) makes the otherwise immunologically
      ignored TRP-2 antigen immunogenic. Tetramer analysis of iso-Asp TRP-2 peptide
      immunized mice demonstrated that CD8+ T cells not only recognized the isoaspartyl
      TRP-2 peptide but also the native TRP-2 peptide. These CD8+ T cells functioned as
      cytotoxic T lymphocytes, as they effectively lysed TRP-2 peptide-pulsed targets
      both in vitro and in vivo. Potentially, post-translational protein modification
      can be utilized to trigger strong immune responses to either tumor proteins or
      potentially weakly immunogenic pathogens.

PMID- 16950787
TI  - Constitutive overexpression of Nrf2-dependent heme oxygenase-1 in A549 cells
      contributes to resistance to apoptosis induced by epigallocatechin 3-gallate.
AB  - Epigallocatechin 3-gallate (EGCG), the major polyphenol found in green tea,
      exerts antiproliferative and proapoptotic effects in many cancer cells. However,
      we found that among many cancer cells human lung adenocarcinoma A549 cells are
      markedly resistant to apoptosis induction by EGCG (even at 100 microm for 72 h).
      Heme oxygenase-1 (HO-1) induced by stress stimuli represents a prime cellular
      defense mechanism, but it may be associated with enhanced cell proliferation and
      chemoresistance in some cancer cells. Because we found that A549 cells
      constitutively overexpress HO-1 and its associated transcription factor Nrf2, we
      tested an hypothesis that EGCG resistance in these cells may be linked with Nrf2
      mediated HO-1 overexpression. HO-1 inhibition with tin-protoporphyrin IX and
      silencing with RNA interference rendered cells more sensitive to apoptosis
      induction by EGCG and classical prooxidants. Interestingly, EGCG at high
      concentration (>200 microm) induced apoptosis by suppressing expression of HO-1
      protein and mRNA, and this effect correlated with a decrease in both Nrf2-ARE
      binding and HO-1-ARE-luciferase activity, suggesting Nrf2-driven transcriptional
      activation of ho-1. Because we observed notably high levels of phosphorylated
      protein kinase C alpha and its suppression by EGCG and deferoxamine (an iron
      chelator), a possible mechanism involving phosphorylated protein kinase C alpha
      and iron in Nrf2-HO-1 activation was further investigated. Collectively, our
      findings suggest that Nrf2-mediated HO-1 overexpression confers resistance to
      apoptosis induction by EGCG; therefore, its inactivation may be a target for
      overcoming the resistance to chemoprevention and chemotherapy.

PMID- 16950788
TI  - Up-regulation of endogenous RGS2 mediates cross-desensitization between Gs and Gq
      signaling in osteoblasts.
AB  - Regulator of G protein signaling (RGS) proteins limit G protein signals. In this
      study, we investigated the role of RGS2 in the control of G protein signaling
      cascades in osteoblasts, the cells responsible for bone formation. Expression of
      RGS2 was up-regulated in primary cultures of mouse calvarial osteoblasts by
      parathyroid hormone-related peptide (PTHrP)-(1-34), which stimulates G(s)
      signaling. RGS2 was also up-regulated by extracellular ATP, which selectively
      activates G(q), as well as by forskolin and phorbol myristate acetate, which
      activate targets downstream of G(s) and G(q), respectively. To assess the role of
      endogenous RGS2, we characterized G(s) and G(q) signaling in osteoblasts derived
      from wild type and rgs2(-/-) mice. Under control conditions, nucleotide
      stimulated calcium release, endothelin-stimulated accumulation of inositol
      phosphates, and PTHrP-stimulated cAMP accumulation were equivalent in osteoblasts
      isolated from wild type and rgs2(-/-) mice. Thus, basal levels of endogenous RGS2
      do not appear to regulate G(s) or G(q) signaling in osteoblasts. Interestingly,
      forskolin treatment of wild type but not rgs2(-/-) osteoblasts suppressed both
      endothelin-stimulated accumulation of inositol phosphates and nucleotide
      stimulated calcium release, indicating that up-regulation of RGS2 by G(s)
      signaling desensitizes G(q) signals. Furthermore, pretreatment with ATP
      suppressed PTHrP-dependent cAMP accumulation in wild type but not rgs2(-/-)
      osteoblasts, implying that up-regulation of RGS2 by G(q) signaling desensitizes
      G(s) signals. Our findings demonstrate that endogenously expressed RGS2 can limit
      G(s) signaling. Moreover, up-regulation of RGS2 contributes to cross
      desensitization of G(s)- and G(q)-coupled signals.

PMID- 16950790
TI  - The polypyrimidine tract-binding protein (PTB) is involved in the post
      transcriptional regulation of human inducible nitric oxide synthase expression.
AB  - Human inducible nitric oxide synthase (iNOS) expression is regulated by
      transcriptional and post-transcriptional mechanisms. We have recently shown that
      the multifunctional RNA-binding proteins KH-type splicing regulatory protein and
      tristetraprolin are critically involved in the post-transcriptional regulation of
      human iNOS expression. Several reports have shown that KH-type splicing
      regulatory protein colocalizes with the polypyrimidine tract-binding protein
      (PTB), and both RNA-binding proteins seem to interact with the same mRNAs.
      Therefore we analyzed the involvement of PTB in human iNOS expression. In human
      DLD-1 cells, cytokine incubation necessary to induce iNOS expression did not
      change PTB localization or expression. However, intracellular binding of PTB to
      the human iNOS mRNA increased after cytokine stimulation. Overexpression of PTB
      resulted in enhanced cytokine-induced iNOS expression. Accordingly, small
      interfering RNA-mediated knock down of PTB reduced cytokine-dependent iNOS
      expression. Recombinant PTB displayed binding to an UC-rich sequence in the 3'
      untranslated region of the human iNOS mRNA. Transfection experiments showed that
      PTB mediates its effect on iNOS expression via binding to this region. The
      underlying mechanism is based on a modulation of iNOS mRNA stability. In summary,
      human iNOS is the first example of a human pro-inflammatory gene regulated by PTB
      on the level of mRNA stability.

PMID- 16950789
TI  - Regulation of bone morphogenetic protein-4 by matrix GLA protein in vascular
      endothelial cells involves activin-like kinase receptor 1.
AB  - Matrix GLA protein (MGP) has previously been shown to enhance expression of
      vascular endothelial growth factor (VEGF) through the activin-like kinase
      receptor 1 (ALK1) in bovine aortic endothelial cells. MGP has also been
      identified as an inhibitor of bone morphogenetic protein-2 (BMP-2). This study
      showed that the effect of MGP on ALK1 signaling and VEGF expression in bovine
      aortic endothelial cells was dose-dependent, that a progressive increase of MGP
      levels ceased to be stimulatory and instead turned inhibitory. We identified a
      new regulatory pathway involving BMP that may explain this response. BMP-2 and
      BMP-4 induced expression of ALK1 in a dose-dependent fashion as determined by
      real-time PCR and immunoblotting. Activation of ALK1 signaling induced expression
      of MGP in addition to that of VEGF, allowing for negative feedback regulation of
      BMP by MGP. MGP inhibited BMP-4 activity similarly to that of BMP-2 and
      interacted with BMP-4 on a protein level as determined by co-immunoprecipitation.
      The dose-dependent effect on ALK1 expression and the stimulation of MGP and VEGF
      expression were dependent on signaling by transforming growth factor-beta (TGF
      beta) and ALK1. Inhibition of TGF-beta by neutralizing antibodies abolished the
      inhibitory effect of high BMP-4 levels on ALK1 expression and the induction of
      MGP and VEGF. Depletion of ALK1 by small interfering RNA abolished the induction
      of MGP and VEGF. MGP promoter activity was also stimulated by BMP-4 in a TGF-beta
      dependent fashion. The results suggest that the effects of BMP on endothelial
      cells occur in part through induction of ALK1, an effect that may be limited by
      ALK1-induced MGP.

PMID- 16950792
TI  - Polycystin-2 cation channel function is under the control of microtubular
      structures in primary cilia of renal epithelial cells.
AB  - Mutations in the gene encoding polycystin-2 (PC2) result in autosomal dominant
      polycystic kidney disease and defects in left-right asymmetry during
      embryogenesis. PC2 is a TRP-type Ca(2+)-permeable non-selective cation channel,
      which is expressed in kidney and other organs. PC2 is present and functional in
      microtubule-containing primary cilia of renal epithelial cells. However, no
      information is yet available as to whether PC2 interacts with microtubules. Here,
      we assessed the role of microtubular dynamics in regulating PC2 channel function
      in primary cilia. Isolated ciliary membranes from LLC-PK1 epithelial cells were
      reconstituted in a lipid bilayer system. The acute addition of the microtubular
      disrupter colchicine (15 mum) rapidly abolished, whereas the addition of the
      microtubular stabilizer paclitaxel (taxol, 15 mum) increased ciliary PC2 channel
      activity. The further addition of alpha-tubulin plus GTP also stimulated PC2
      channel activity in ciliary membranes. However, alpha-tubulin and GTP had no
      effect on in vitro translated PC2. Using the yeast two-hybrid assay, we found
      that PC2 interacts with the microtubule-dependent motor kinesin-2 subunit KIF3A,
      a protein involved in polycystic kidney disease. The interaction occurred through
      the carboxyl termini domain of both proteins, which was further confirmed by in
      vitro glutathione S-transferase pull-down and dot blot overlay assays. Co
      immunoprecipitation experiments showed that PC2 and KIF3A are in the same complex
      in native HEK293, Madin-Darby canine kidney cells (MDCK), and LLC-PK1 cells.
      Immunofluorescent staining also showed substantial PC2 and KIF3A co-localization
      in primary cilia of renal epithelial cells. The data indicate that microtubular
      organization regulates PC2 function, which may explain, among others, the
      regulatory role of PC2 in the sensory function of primary cilia.

PMID- 16950791
TI  - Role of Hcn1 and its phosphorylation in fission yeast anaphase-promoting
      complex/cyclosome function.
AB  - The anaphase-promoting complex/cyclosome (APC/C) is a conserved multisubunit
      ubiquitin ligase required for the degradation of key cell cycle regulators. The
      APC/C becomes active at the metaphase/anaphase transition and remains active
      during G(1) phase. One mechanism linked to activation of the APC/C is
      phosphorylation. Although many sites of mitotic phosphorylation have been
      identified in core components of the APC/C, the consequence of any individual
      phosphorylation event has not been elucidated in vivo. In this study, we show
      that Hcn1 is an essential core component of the fission yeast APC/C and is
      critical for maintaining complex integrity. Moreover, Hcn1 is a phosphoprotein in
      vivo. Phosphorylation of Hcn1 occurs at a single Cdk1 site in vitro and in vivo.
      Mutation of this site to alanine, but not aspartic acid, compromises APC/C
      function and leads to a specific defect in the completion of cell division.

PMID- 16950793
TI  - Identification of acid-base catalytic residues of high-Mr thioredoxin reductase
      from Plasmodium falciparum.
AB  - High-M(r) thioredoxin reductase from the malaria parasite Plasmodium falciparum
      (PfTrxR) contains three redox active centers (FAD, Cys-88/Cys-93, and Cys-535/Cys
      540) that are in redox communication. The catalytic mechanism of PfTrxR, which
      involves dithiol-disulfide interchanges requiring acid-base catalysis, was
      studied by steady-state kinetics, spectral analyses of anaerobic static
      titrations, and rapid kinetics analysis of wild-type enzyme and variants
      involving the His-509-Glu-514 dyad as the presumed acid-base catalyst. The dyad
      is conserved in all members of the enzyme family. Substitution of His-509 with
      glutamine and Glu-514 with alanine led to TrxR with only 0.5 and 7% of wild type
      activity, respectively, thus demonstrating the crucial roles of these residues
      for enzymatic activity. The H509Q variant had rate constants in both the
      reductive and oxidative half-reactions that were dramatically less than those of
      wild-type enzyme, and no thiolateflavin charge-transfer complex was observed. Glu
      514 was shown to be involved in dithiol-disulfide interchange between the Cys
      88/Cys-93 and Cys-535/Cys-540 pairs. In addition, Glu-514 appears to greatly
      enhance the role of His-509 in acid-base catalysis. It can be concluded that the
      His-509-Glu-514 dyad, in analogy to those in related oxidoreductases, acts as the
      acid-base catalyst in PfTrxR.

PMID- 16950794
TI  - Separating the anti-apoptotic and mitotic roles of survivin.
AB  - Survivin is a bifunctional protein that acts as a suppressor of apoptosis and has
      an essential role in mitosis. To date whether these two functions can be divorced
      has not been addressed. Here we show that the linker region between the BIR
      (baculovirus inhibitor of apoptosis repeat) domain of survivin and COOH-terminal
      alpha helix may be the key to separating its roles. When overexpressed survivin
      is present in interphase cells and shuttles between the cytoplasm and nucleus.
      Here we identify a rev-like nuclear exportation signal (NES) in the central
      domain of survivin and demonstrate that point mutations within this region cause
      accumulation of survivin in the nucleus. Interestingly cells expressing NES
      mutants exhibit reduced survival after X-irradiation. Moreover, cells expressing
      survivin(L98A)-green fluorescent protein (GFP) showed increased poly(ADP-ribose)
      polymerase-cleavage and caspase-3 activity after tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) treatment compared with cells expressing full
      length survivin-green fluorescent protein. These data suggest a direct link
      between the interphase localization of survivin and cellular responsiveness to
      apoptotic stimuli. Using a cell proliferation assay, we also found that ectopic
      expression of NES mutants can complement for depletion of endogenous survivin,
      indicating that they can execute the mitotic duties of survivin. Thus we
      demonstrate for the first time that 1) survivin has a functional NES; 2) nuclear
      accumulation of overexpressed survivin correlates with increased sensitivity of
      cells to ionising radiation; and 3) the anti-apoptotic and mitotic roles of
      survivin can be separated through mutation of its NES. Separating these two
      functions of survivin could open up new possibilities for therapeutic strategies
      aimed at eliminating cancer cells yet preserving normal cell viability.

PMID- 16950795
TI  - cis-9,trans-11-conjugated linoleic acid down-regulates phorbol ester-induced NF
      kappaB activation and subsequent COX-2 expression in hairless mouse skin by
      targeting IkappaB kinase and PI3K-Akt.
AB  - Conjugated linoleic acid (CLA) has been reported to inhibit mouse skin
      carcinogenesis, particularly in the promotion stage, but underlying molecular
      mechanisms remain poorly understood. Since persistent induction of cyclooxygenase
      2 (COX-2) is frequently implicated in carcinogenesis, we investigated the effect
      of cis-9,trans-11-CLA (9Z,11E-CLA) on the tumor promoter-induced COX-2 expression
      in HR-1 hairless mouse skin in vivo. Topical application of 9Z,11E-CLA caused
      significant inhibition of COX-2 expression at 6 h induced by 10 nmol 12-O
      tetradecanoylphorbol-13-acetate (TPA) in HR-1 mouse skin. Since NF-kappaB is
      known to regulate COX-2 gene expression, we determined the effect of 9Z,11E-CLA
      on TPA-induced activation of this transcription factor. Treatment of mouse skin
      with 9Z,11E-CLA reduced TPA-induced DNA binding as well as nuclear translocation
      of NF-kappaB by blocking phosphorylation and subsequent degradation of
      IkappaBalpha. In addition, 9Z,11E-CLA attenuated TPA-induced phosphorylation of
      extracellular signal-regulated protein kinase, p38 mitogen-activated protein
      kinase and Akt. To further elucidate the molecular mechanism underlying the
      inactivation of NF-kappaB by 9Z,11E-CLA, we investigated its effect on TPA
      induced activation of IkappaB kinase (IKK), an upstream kinase that regulates NF
      kappaB via phosphorylation and degradation of IkappaBalpha. 9Z,11E-CLA treatment
      down-regulated phosphorylation and catalytic activities of IKKalpha/beta in TPA
      treated mouse skin. Co-treatment of mouse skin with the IKKbeta-specific
      inhibitor SC-514 (1 micromol) attenuated TPA-induced activation of Akt and NF
      kappaB, and also the expression of COX-2 in hairless mouse skin. Taken together,
      9Z,11E-CLA inhibits NF-kappaB driven-COX-2 expression by blocking the IKK and
      PI3K-Akt signaling in TPA-treated hairless mouse skin in vivo, which may account
      for its previously reported anti-tumor promoting effects.

PMID- 16950796
TI  - Increased expression of the MGMT repair protein mediated by cysteine prodrugs and
      chemopreventative natural products in human lymphocytes and tumor cell lines.
AB  - O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein which
      protects the cellular genome and critical oncogenic genes from the mutagenic
      action of endogenous and exogenous alkylating agents. An expedited elimination of
      O6-alkylguanines by increasing MGMT activity levels is likely to be a successful
      chemoprevention strategy. Here, we report for the first time that
      cysteine/glutathione enhancing drugs and certain plant antioxidants possess the
      ability to increase human MGMT expression beyond its steady-state levels that may
      afford protection. The non-toxic cysteine prodrugs, 2-oxothiazolidine-4
      carboxylic acid (OTC) and N-acetyl-L-cysteine (NAC), metabolized, respectively by
      5-oxoprolinase and acylases, increased the MGMT protein and its repair activity
      levels in a dose- and time-dependent manner in several cancer cell lines and
      peripheral blood lymphocytes with a maximum of 3-fold increase by 72 h. The
      natural antioxidants, namely, curcumin, silymarin, sulforaphane and resveratrol
      were also effective in raising the MGMT levels to different extents. Among the
      synthetic agents, oltipraz and N-(4-hydroxyphenyl) retinamide (4-HPR) also
      increased MGMT expression, albeit to a lesser extent. Augmented mRNA levels
      accounted at least, in part, for the increased activity of MGMT in this setting.
      However, evidence from cysteine/methionine deprivation, acivicin treatment, and
      protein synthesis measurements in OTC-treated cells suggested that an increased
      cysteine flux also contributed significantly to enhanced MGMT expression. Many of
      these treatments increased the glutathione S-transferase-P1 (GSTP1) levels as
      well. These findings raise the possibility of MGMT-targeted chemoprevention
      strategies through dietary supplementation of OTC and herbal antioxidants.
      Further, the studies reveal the antioxidant responsiveness of the human MGMT
      gene.

PMID- 16950797
TI  - Hsp70 protects against UVB induced apoptosis by preventing release of cathepsins
      and cytochrome c in human melanocytes.
AB  - Stress-induced heat shock protein 70 (Hsp70) effectively protects cells against
      apoptosis, although the anti-apoptotic mechanism is still undefined. Exposure of
      human melanocytes to heat and subsequent UVB irradiation increased the level of
      Hsp70 and pre-heating reduced UVB induced apoptosis. Immunofluorescence staining
      of Hsp70 in combination with staining of lysosomes (Lamp2) or mitochondria
      (Mitotracker) in pre-heated UVB exposed cells showed co-localization of Hsp70
      with both lysosomes and mitochondria in the surviving cell population.
      Furthermore, UVB induced apoptosis was accompanied by lysosomal and mitochondrial
      membrane permeabilization, detected as release of cathepsin D and cytochrome c,
      respectively, which were prevented by heat pre-treatment. In purified fractions
      of lysosomes and mitochondria, recombinant Hsp70 attached to both lysosomal and
      mitochondrial membranes. Moreover, in apoptotic cells Bax was translocated from a
      diffuse cytosolic location into punctate mitochondrial-like structures, which was
      inhibited by Hsp70 induction. Such inhibition of Bax translocation was abolished
      by transfection with Hsp70 siRNA. Furthermore, Hsp70 siRNA eliminated the
      apoptosis preventive effect observed after pre-heating. These findings show Hsp70
      to rescue melanocytes from UVB induced apoptosis by preventing release of
      cathepsins from lysosomes, Bax translocation and cytochrome c release from
      mitochondria.

PMID- 16950798
TI  - 4-monochlorobiphenyl (PCB3) induces mutations in the livers of transgenic Fisher
      344 rats.
AB  - 4-monochlorobiphenyl (PCB3) is found in small amounts in commercial PCB mixtures,
      indoor and outdoor air, and in food. In contrast to highly chlorinated congeners
      that are more resistant to metabolic attack, PCB3 is more readily converted by
      xenobiotic-metabolizing enzymes to monohydroxy-PCBs and further to dihydroxy
      metabolites, which can be oxidized to quinones. Our recent studies demonstrated
      the initiating action of PCB3 in the livers of male rats. Therefore we
      hypothesized that PCB3 and/or its metabolite(s) are mutagenic in rat livers in
      vivo. To investigate the mutagenicity and the types of mutations generated by
      PCB3, male Fischer 344 BigBlue rats, transgenic for the lacI gene, were injected
      intraperitoneally with PCB3 (600 micromol/kg), 4-hydroxy-PCB3 (4-HO-PCB3, 400
      micromol/kg), 3-methylcholanthrene (3-MC, 300 micromol/kg, positive control) and
      corn oil (negative control) once per week, for 4 weeks. Animals were killed 17
      days after the last injection and the mutant frequency of the liver lacI gene
      determined. 3-MC induced a 4-fold increase of the mutant frequency of the lacI
      gene in the liver. The mutant frequency in PCB3-treated animals was also
      significantly elevated. In contrast, 4-HO-PCB3 induced a non-significant doubling
      of the mutant frequency. The mutation spectrum of solvent control mutants was
      characterized by transitions, whereas in 3-MC-animals, transversion and
      frameshift mutations predominated. The PCB3-induced mutation spectrum was similar
      to that of the 3-MC-induced mutants. In contrast, the mutation spectrum of the 4
      HO-PCB3 group hardly differed from that of the control animals. This study
      demonstrates for the first time the mutagenicity of a PCB in vivo.

PMID- 16950799
TI  - Association of p73 G4C14-to-A4T14 (GC/AT) polymorphism with breast cancer
      survival.
AB  - p73 gene shares structural and functional similarities to p53, and plays an
      important role in modulating cell-cycle arrest and apoptosis. A common non-coding
      polymorphism of exon 2 of the p73 gene (designated as GC/AT) may affect gene
      expression, thus, it may lead to functional significance. The correlation of this
      polymorphism with breast cancer survival has not been investigated. In this
      study, by using genomic DNA p73 GC/AT polymorphism was detected by PCR-SSCP in
      526 breast cancer patients with a median follow-up of 7.3 years. Among the 526
      breast cancer patients, 4% of the patients were homozygous for the AT/AT
      genotype, 39% were heterozygous GC/AT and 57% were homozygous for the GC/GC
      genotype. We found that patients with the GC/GC genotype had a significantly
      worse clinical outcome than did patients with the AT Variants (AT/AT or GC/AT
      genotype) (5-year disease-free survival, 74.2 versus 95.0 or 84.1%, P=0.02; 5
      year overall survival, 78.9 versus 95.0 or 87.5%, P=0.01, respectively). As
      compared with the GC/AT and AT/AT genotypes, the GC/GC genotype remained an
      independent prognostic indicator of disease-free survival (HR 1.82, P=0.003) and
      overall survival (HR 1.99, P=0.004) in multivariate analysis. Our results suggest
      that the GC/GC genotype is significantly associated with poor prognosis in breast
      cancer and raise the possibility that analysis of p73 polymorphism may provide
      useful prognostic information for breast cancer patients. Additional independent
      studies are needed to confirm these findings.

PMID- 16950800
TI  - Polymorphisms in the MTHFR and VDR genes and skin cancer risk.
AB  - Folate and vitamin D have been shown to be influenced by ultraviolet (UV)
      radiation. UVA radiation can break down plasma folate, whereas vitamin D can be
      synthesized in UVB-exposed skin. Folate metabolism is involved in DNA synthesis
      and repair, and vitamin D processes anti-proliferative effects. The functions of
      both nutrients are implicated in skin carcinogenesis. We evaluated genetic
      polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene (C677T and
      A1298C) and the vitamin D receptor (VDR) gene (Fok1, Bsm1 and Cdx2) with skin
      cancer risk in a nested case-control study within the Nurses' Health Study [219
      melanoma, 286 squamous cell carcinoma (SCC), 300 basal cell carcinoma (BCC) and
      873 controls]. No significant associations were observed for the two MTHFR
      polymorphisms on skin cancer risk. We observed an interaction between the C677T
      polymorphism and total folate intake on SCC risk (P, interaction=0.04); the
      highest risk was observed among women with TT genotype and low folate intake
      (OR=2.14; 95% CI=1.01-4.50). The VDR Bsm1 BB genotype was significantly
      associated with an increased SCC risk (OR=1.51; 95% CI=1.00-2.28). An interaction
      between the Bsm1 polymorphism and total vitamin D intake on SCC was observed,
      with the highest risk seen in women with the BB genotype and high vitamin D
      intake (OR=2.38; 95% CI=1.22-4.62) (P, interaction=0.08). This study suggests a
      possible role of the polymorphisms in MTHFR and VDR interacting with dietary
      intakes of folate and vitamin D in skin cancer development, especially for SCC.
      Due to a large number of comparisons and tests, the possible associations should
      be interpreted with caution and confirmed by other studies.

PMID- 16950801
TI  - Mutations in progranulin are a major cause of ubiquitin-positive frontotemporal
      lobar degeneration.
AB  - Null mutations in the progranulin gene (PGRN) were recently reported to cause tau
      negative frontotemporal dementia linked to chromosome 17. We assessed the genetic
      contribution of PGRN mutations in an extended population of patients with
      frontotemporal lobar degeneration (FTLD) (N=378). Mutations were identified in
      10% of the total FTLD population and 23% of patients with a positive family
      history. This mutation frequency dropped to 5% when analysis was restricted to an
      unbiased FTLD subpopulation (N=167) derived from patients referred to Alzheimer's
      Disease Research Centers (ADRC). Among the ADRC patients, PGRN mutations were
      equally frequent as mutations in the tau gene (MAPT). We identified 23 different
      pathogenic PGRN mutations, including a total of 21 nonsense, frameshift and
      splice-site mutations that cause premature termination of the coding sequence and
      degradation of the mutant RNA by nonsense-mediated decay. We also observed an
      unusual splice-site mutation in the exon 1 5' splice site, which leads to loss of
      the Kozac sequence, and a missense mutation in the hydrophobic core of the PGRN
      signal peptide. Both mutations revealed novel mechanisms that result in loss of
      functional PGRN. One mutation, c.1477C>T (p.Arg493X), was detected in eight
      independently ascertained familial FTLD patients who were shown to share a common
      extended haplotype over the PGRN genomic region. Clinical examination of patients
      with PGRN mutations revealed highly variable onset ages with language dysfunction
      as a common presenting symptom. Neuropathological examination showed FTLD with
      ubiquitin-positive cytoplasmic and intranuclear inclusions in all PGRN mutation
      carriers.

PMID- 16950802
TI  - Dipsogenic genes associated with weight changes during Ironman Triathlons.
AB  - Thirst is regulated by a complex interaction of signalling pathways within the
      central nervous system, including components of the renin-angiotensin and
      kalikrein kinin systems, as well as the serotonergic pathways. The aim of this
      study was to determine whether there were any associations between polymorphisms
      within the ACE, BDKRB2, NOS3 and/or 5-HTT genes with weight changes during the
      2000 and 2001 226 km South African Ironman Triathlons. Pre- and post-race serum
      [Na(+)] and body weights, as well as genotype data, were collected from 428
      (61.1%) Caucasian male triathletes who were divided into three groups according
      to their relative weight loss during the triathlon (0-3, 3-5 and >5%). There was
      a significant linear trend for the distribution of both the BDKRB2 +9/+9 genotype
      and the 5-HTT SS genotype between the three weight loss groups, with the >5%
      group having the highest percentage of athletes with the +9/+9 genotype
      (chi(2)=5.3, P=0.021) and the highest percentage of athletes with the SS genotype
      (chi(2)=5.8, P=0.016). Likewise, the >5% group had the highest percentage of
      athletes with the combined SS 5-HTT and/or +9/+9 BDKRB2 genotypes (chi(2)=7.4,
      P=0.007). In conclusion, the functional SS genotype of the serotonin transporter
      linked polymorphic region (5-HTTLPR) within the 5-HTT gene and the functional
      +9/+9 genotype of the BDKBR2 gene were associated with larger weight losses
      during the Ironman Triathlons. These findings suggest the involvement of the
      serotonergic pathways in the control of thirst and drinking behaviour and provide
      further evidence for the dipsogenic effect of circulating bradykinin.

PMID- 16950803
TI  - Re: Reduction of broad-spectrum antibiotic use with computerized decision support
      in an intensive care unit.

PMID- 16950804
TI  - Comparison of health care professionals' and surveyors' opinions on problems and
      obstacles in implementing quality management system in Thailand: A national
      survey.
AB  - OBJECTIVE: To explore problems and obstacles of hospitals in Thailand
      implementing quality management systems according to the hospital accreditation
      (HA) standards. DESIGN: Questionnaire survey. SETTING: Thirty-nine hospitals in
      all 13 regions of Thailand. PARTICIPANTS: A total of 728 health care
      professionals and 41 surveyors of the national accreditation program. MAIN
      OUTCOME MEASURES: Health care professionals' and surveyors' opinions on problems
      and obstacles in 24 items representing Thailand HA standards. RESULTS: The
      response rates were 94.9 and 73.2% in health care professionals and surveyors,
      respectively. More than 90% of both groups thought that there had been problems
      in the items such as 'quality improvement (QI) activities' and 'integration and
      utilization of information'. The items considered by health care professionals as
      major obstacles included 'adequacy of staff' (34.6%) and 'integration and
      utilization of information' (26.6%), for example. For surveyors, 'integration and
      utilization of information' was ranked highest as presenting a major obstacle
      (43.9%), followed by 'discharge and referral process' (31.7%) and 'medical
      recording process' (29.3%). The rank orders for the 24 items as problems and
      major obstacles were similar in both groups (Spearman's rank correlation 0.436, P
      = 0.033 and 0.583, P = 0.003, respectively). Surveyors had a higher degree of
      concern and paid more attention to care-related items than health care
      professionals. CONCLUSIONS: Health care professionals have been facing many
      problems with multidisciplinary process-related issues of the accreditation
      standard, whereas surveyors might have had some difficulties in conveying the
      core QI concepts to them. The findings might be explained by the effects of
      health care reform on the underlying accreditation principles. One of the
      strategies to respond to the situation was presented.

PMID- 16950805
TI  - Effects of folic acid deficiency and MTHFR C677T polymorphism on spontaneous and
      radiation-induced micronuclei in human lymphocytes.
AB  - Folic acid plays a key role in the maintenance of genomic stability, providing
      methyl groups for the conversion of uracil to thymine and for DNA methylation.
      Besides dietary habits, folic acid metabolism is influenced by genetic
      polymorphism. The C677T polymorphism of the methylene-tetrahydrofolate reductase
      (MTHFR) gene is associated with a reduction of catalytic activity and is
      suggested to modify cancer risk differently depending on folate status. In this
      work the effect of folic acid deficiency on genome stability and radiosensitivity
      has been investigated in cultured lymphocytes of 12 subjects with different MTHFR
      genotype (four for each genotype). Cells were grown for 9 days with 12, 24 and
      120 nM folic acid and analyzed in a comprehensive micronucleus test coupled with
      centromere characterization by CREST immunostaining. In other experiments, cells
      were grown with various folic acid concentrations, irradiated with 0.5 Gy of
      gamma rays and analyzed in the micronucleus test. The results obtained indicate
      that folic acid deficiency induces to a comparable extent chromosome loss and
      breakage, irrespective of the MTHFR genotype. The effect of folic acid was highly
      significant (P < 0.001) and explained >50% of variance of both types of
      micronuclei. Also nucleoplasmic bridges and buds were significantly increased
      under low folate supply; the increase in bridges was mainly observed in TT cells,
      highlighting a significant effect of the MTHFR genotype (P = 0.006) on this
      biomarker. Folic acid concentration significantly affected radiation-induced
      micronuclei (P < 0.001): the increased incidence of radiation-induced micronuclei
      with low folic acid was mainly accounted for by carriers of the variant MTHFR
      allele (both homozygotes and heterozygotes), but the overall effect of genotype
      did not attain statistical significance. Treatment with ionizing radiations also
      increased the frequency of nucleoplasmic bridges. The effect of folic acid level
      on this end-point was modulated by the MTHFR genotype (P for interaction = 0.02),
      with TT cells grown at low folic acid concentration apparently resistant to the
      induction of radiation-induced bridges. Finally, the effect of in vitro folate
      deprivation on global DNA methylation was evaluated in lymphocytes of six
      homozygous subjects (three CC and three TT). The results obtained suggest that,
      under the conditions of this work, folic acid deprivation is associated with
      global DNA hypermethylation.

PMID- 16950806
TI  - Topoisomerase II inhibition and high yield of endoreduplication induced by the
      flavonoids luteolin and quercetin.
AB  - Luteolin and quercetin are widely distributed plant flavonoids that possess a
      variety of chemical and biological activities, including free-radical scavenging
      and antioxidant activity. Recently, both flavonoids have been reported to inhibit
      DNA topoisomerases I and II (topo I and topo II), a property that, together with
      their ability to induce DNA and chromosome damage, has made them candidate
      anticancer compounds. In the present study, we confirmed that both compounds are
      topo II inhibitors by conducting a comparative study of their effect on topo II
      activity from Chinese hamster ovary AA8 cells. Because interference with the
      function of topo II to resolve DNA entanglement at the end of replication results
      in chromosome malsegregation at mitosis, we investigated whether luteolin and
      quercetin are effective in inducing endoreduplication in AA8 cells.
      Concentrations of luteolin and quercetin that inhibited topo II catalytic
      activity resulted in extraordinarily high yields of metaphases showing
      diplochromosomes. Given the established relationship of polyploidy with tumor
      development via aneuploidy and genetic instability, these results question the
      usefulness of luteolin and quercetin in cancer therapy.

PMID- 16950807
TI  - Mothers with their babies in prison: the first Italian experience.

PMID- 16950808
TI  - Tolerance and efficacy of rituximab and changes in serum B cell biomarkers in
      patients with systemic complications of primary Sjogren's syndrome.
AB  - OBJECTIVE: To investigate the safety and efficacy of rituximab (RTX) for systemic
      symptoms in patients with primary Sjogren's syndrome (pSS), and changes in B cell
      biomarkers. PATIENTS AND METHODS: The records of 16 patients with pSS according
      to the American European consensus group criteria were reviewed retrospectively.
      RESULTS: Patients, all women, had a median age of 58.5 (range 41-71) years and a
      disease duration of 9.5 (range 0-25) years. RTX was prescribed for lymphoma (n =
      5), refractory pulmonary disease with polysynovitis (n = 2), severe polysynovitis
      (n = 2), mixed cryoglobulinaemia (n = 5), thrombocytopenia (n = 1) and
      mononeuritis multiplex (n = 1). The median follow-up duration was 14.5 (range 2
      48) months. Three patients experienced adverse events, including one mild serum
      sickness-like reaction with the presence of human antichimeric antibodies.
      Efficacy of treatment was observed in 4 of 5 patients with lymphomas and in 9 of
      11 patients with systemic involvement. Dryness was improved in only a minority of
      patients. Corticosteroid dose was reduced in 11 patients. RTX induced decreased
      rheumatoid factor, gamma-globulin and beta2-microglobulin levels, and the level
      of B cell activating factor of the tumour necrosis factor family (BAFF) increased
      concomitantly with B cell depletion. Five patients were re-treated, with good
      efficacy and tolerance, except for one with probable serum sickness-like
      reaction. CONCLUSION: This study shows good efficacy and fair tolerance of RTX
      for systemic features. In addition, RTX allows for a marked reduction in
      corticosteroid use. Except for BAFF, the level of which increases, serum B cell
      biomarker levels decrease after taking RTX. Controlled trials should be performed
      to confirm the efficacy of RTX in pSS.

PMID- 16950809
TI  - Haematopoietic stem cell transplantation for vasculitis including Behcet's
      disease and polychondritis: a retrospective analysis of patients recorded in the
      European Bone Marrow Transplantation and European League Against Rheumatism
      databases and a review of the literature.
AB  - OBJECTIVE: To evaluate the feasibility of haematopoietic stem cell
      transplantation (HSCT) in vasculitis. METHODS: This is a retrospective analysis
      of patients who had received HSCT for vasculitic diseases and have been reported
      to the European League Against Rheumatism autoimmune disease or European Bone
      Marrow Transplantation ProMISe databases. Information about the disease and
      outcome was obtained by a questionnaire sent to the referring centres. Response
      of the disease to HSCT was defined as partial or complete responses according to
      the ability to reduce immunosuppression after HSCT. In addition, the Medline
      database was searched for reports on HSCT in patients with vasculitis. RESULTS:
      Detailed information was obtained for 15 patients, whose median age at HSCT was
      37 years. The diagnoses were cryoglobulinaemia in four patients, Behcet's disease
      in three patients, Wegener's granulomatosis in three patients, and
      undifferentiated vasculitis, Churg-Strauss angiitis, polychondritis, Takayasu
      arteritis and polyarteritis nodosa in one patient each. 14 patients received
      autologous HSCT and 1 an allogeneic HSCT as the first transplant. In three
      patients, further transplantation was given because of relapse. The overall
      response, including all consecutive transplantations (HSCT/patient, n = 1-3,
      median 1.3) to HSCT, was 93%, with 46% complete responses and 46% partial
      responses; median (range) duration of response at the time of reporting was 45
      (16-84) months. Three patients died, one from advanced disease, one from cancer
      and one from graft-versus-host disease. The Medline search showed five other
      patients who were effectively treated with HSCT for vasculitic diseases.
      CONCLUSION: This retrospective study suggests that autologous HSCT is feasible
      for vasculitis. Its value remains to be tested in prospective controlled studies.

PMID- 16950810
TI  - Increasing age at symptom onset is associated with worse radiological damage at
      presentation in patients with early inflammatory polyarthritis.
AB  - BACKGROUND: Increasing age at onset has been associated with worse outcome in
      rheumatoid arthritis, although there are few data from unselected inception
      cohorts. HYPOTHESIS: Increasing age is associated with a higher risk of erosions
      at presentation, and this increase is not explained by age-related disease
      confounders. SUBJECTS AND METHODS: 222 subjects (median onset age 59 years) were
      studied from a primary-care-based register of new-onset inflammatory
      polyarthritis. Patients had hand and feet radiographs taken within 12 months from
      symptom onset. Films were scored by two readers using the Larsen score. The risk
      of erosions in those aged 50-69 and >or=70 years at onset was compared with the
      risk in those aged <50 years both before and after adjustment for possible age
      related disease confounders. RESULT: The prevalences of erosions were 22%, 52%
      and 71% in those aged <50, 50-69 and >or=70 years at onset equivalent to odds
      ratios (ORs) (95% confidence intervals (CIs)) of 3.5 (2.2 to 5.7) and 7.4 (4.5 to
      12.1), respectively, in the two older age groups. Excluding those with proximal
      interphalangeal (PIP) erosions alone (due to possible osteoarthritis) did not
      alter these findings. Adjustments for disease characteristics using logistic
      regression did not attenuate these findings: adjusted ORs (95% CIs) 3.6 (2.1 to
      6.1) and 6.9 (3.8 to 12.2) for age groups 50-69 and >or=70 years, respectively.
      The influence of age was stronger than most of the disease-related variables in
      predicting erosions in this cohort. CONCLUSION: Increasing age at symptom onset
      is strongly associated with higher occurrence of erosions within the first year
      unexplained by greater disease severity.

PMID- 16950811
TI  - Anaesthetist's responses to patients' self-reported drug allergies.
AB  - BACKGROUND: Patients with drug allergies are commonplace in anaesthetic practice.
      We investigated the incidence and nature of drug 'allergies' reported by surgical
      patients attending a hospital pre-admission clinic, and went on to ascertain to
      what degree drug allergies recorded in the records influenced drug prescribing
      during the patients' hospital stay and determine whether any adverse events
      occurred in relation to drug prescribing in this population. METHODS: Patients
      attending for anaesthetic assessment at a Pre-Admission Clinic over a 30 week
      period were questioned concerning drug allergies. Medical records of these
      patients were then examined after their hospitalization to assess medications
      prescribed during that period. RESULTS: Of 1260 patients attending the Pre
      admission clinic during the study period 420 (33.4%) claimed to have a total of
      644 individual drug 'allergies'. The most common agents implicated were
      antibiotics (n=272), opioid analgesics (n=118) and NSAIDs (n=62); the most common
      form of these reactions were dermatological (n=254) and nausea and vomiting
      (n=124). There were 41 self-reports specifically of anaphylaxis and a further 61
      where there was significant respiratory system involvement. CONCLUSIONS: The
      majority of the self-reported allergies were in fact simply accepted adverse
      effects of the drugs concerned. The patients' reported drug 'allergy' history was
      generally well respected by anaesthetists and other medical staff. There were 13
      incidents, mainly involving morphine, where patients were given a drug to which
      they had claimed a specific allergy. There were 101 incidents in 89 patients
      where drugs of the same pharmacological group as that of their allergic drug were
      used. There were no untoward reactions in 84 patients who had claimed a prior
      adverse reaction to penicillin who were given cephalosporins. There were no
      sequelae from any other events. While anaesthetists generally respected patients
      self-reported 'allergies', more attention needs to be paid to the accurate
      recording of patients' events and a clear distinction should be made both in
      medical records and to the patient between true drug allergy and simple adverse
      drug reactions.

PMID- 16950812
TI  - Alzheimer's disease and anaesthesia: implications for the central cholinergic
      system.
AB  - Alzheimer's disease (AD) is associated with a loss of cholinergic neurons
      resulting in profound memory disturbances and irreversible impairment of
      cognitive function. The central cholinergic system is involved in the action of
      general anaesthetic agents. Anaesthetic modulation of cholinergic transmission
      has profound effects on brain function via a cascade of synaptic and postsynaptic
      events by binding both nicotinic and muscarinic receptors. During general
      anaesthesia, decrease in acetylcholine release and depression of cholinergic
      transmission facilitates the desirable effects of general anaesthetics, such as
      loss of consciousness, pain, voluntary movements and memory. From this point of
      view, patients with AD, characterized by a compromised neuronal transmission,
      represent particular cases in which the choice of anaesthesia drugs may have a
      negative effect on the postoperative outcome. A future challenge may be the
      identification of brain targets of general anaesthetics which do not expose
      patients to postoperative cognitive dysfunction, nor interfere with prognosis of
      brain degenerative disease.

PMID- 16950814
TI  - Methylation analysis of KvDMR1 in human oocytes.
AB  - Recently, several reports have been published that showed a higher incidence of
      assisted reproductive technologies (ART) in patients with Beckwith-Wiedemann
      syndrome compared with the general population, and in most of these patients,
      aberrant methylation imprints of KvDMR1 have been found. This has led to the
      concern that ART might increase the incidence of imprinting syndromes such as
      Beckwith-Wiedemann syndrome. Not much is known on environmental or genetic
      factors that may interfere with the processes of imprint maintenance or
      resetting. A methylation analysis of KvDMR1 was performed in human oocytes at
      different stages of nuclear maturity and in sperm cells. The results indicate
      that the maternal methylation imprints were already established at the germinal
      vesicle stage, whereas all sperm cells were unmethylated, thereby showing that
      the KvDMR1 carries a germline methylation imprint. For one of the oocytes
      analysed, an unmethylated pattern was found, which highlights the need for
      further molecular studies that consider the safety of ART.

PMID- 16950813
TI  - IRAK4 and NEMO mutations in otherwise healthy children with recurrent invasive
      pneumococcal disease.
AB  - BACKGROUND: About 2% of childhood episodes of invasive pneumococcal disease (IPD)
      are recurrent, and most remain unexplained. OBJECTIVE: To report two cases of
      otherwise healthy, unrelated children with recurrent IPD as the only clinical
      infectious manifestation of an inherited disorder in nuclear factor-kappaB(NF
      kappaB)-dependent immunity. RESULTS: One child carried two germline mutations in
      IRAK4, and had impaired cellular responses to interleukin (IL)1 receptor and toll
      like receptor (TLR) stimulation. The other child carried a hemizygous mutation in
      NEMO, associated with a broader impairment of NF-kappaB activation, with an
      impaired cellular response to IL-1R, TLR and tumour necrosis factor receptor
      stimulation. The two patients shared a narrow clinical phenotype, associated with
      two related but different genotypes. CONCLUSIONS: Otherwise healthy children with
      recurrent IPD should be explored for underlying primary immunodeficiencies
      affecting the IRAK4-dependent and NEMO-dependent signalling pathways.

PMID- 16950815
TI  - Genomewide scans of red cell indices suggest linkage on chromosome 6q23.
AB  - BACKGROUND: The red cell indices quantify the size, number and oxygen-carrying
      ability of erythrocytes. Although the genetic basis of many monogenic forms of
      anaemia is well understood, comparatively little is known about the genes
      responsible for variation in the red cell indices among healthy participants.
      OBJECTIVE: To identify quantitative trait loci (QTLs) responsible for normal
      variation in the red cell indices of 391 pairs of dizygotic twins who were
      measured longitudinally at 12, 14 and 16 years of age. RESULTS: Evidence
      suggesting linkage of red cell indices to haemoglobin concentration (LOD = 3.03)
      and haematocrit (LOD = 2.95) on chromosome 6q23, a region previously identified
      as possibly harbouring a QTL for haematocrit, was found. Evidence for linkage to
      several other regions of the genome, including chromosome 4q32 for red cell count
      and 7q for mean cell volume, was also found. In contrast, there was little
      evidence of linkage to the chromosomal regions containing the genes for
      erythropoietin (7q21) and its receptor (19p13.2), nor to the regions containing
      the genes for the haemoglobin alpha (16p13.3) and beta chains (11p15.5).
      CONCLUSION: Findings provide additional evidence for a QTL affecting haemoglobin
      and haematocrit on chromosome 6q23. In contrast, polymorphisms in the genes
      coding for erythropoietin, its receptor and the haemoglobin alpha and beta chains
      do not appear to contribute substantially to variation in the red cell indices
      between healthy persons.

PMID- 16950816
TI  - Depletion of mitochondrial DNA in leucocytes harbouring the 3243A->G mtDNA
      mutation.
AB  - BACKGROUND: The 3243A-->G MTTL1 mutation is the most common heteroplasmic
      mitochondrial DNA (mtDNA) mutation associated with disease. Previous studies have
      shown that the percentage of mutated mtDNA decreases in blood as patients get
      older, but the mechanisms behind this remain unclear. OBJECTIVES AND METHOD: To
      understand the dynamics of the process and the underlying mechanisms, an accurate
      fluorescent assay was established for 3243A-->G heteroplasmy and the amount of
      mtDNA in blood with real-time polymerase chain reaction was determined. The
      amount of mutated and wild-type mtDNA was measured at two time points in 11
      subjects. RESULTS: The percentage of mutated mtDNA decreases exponentially during
      life, and peripheral blood leucocytes in patients harbouring 3243A-->G are
      profoundly depleted of mtDNA. CONCLUSIONS: A similar decrease in mtDNA has been
      seen in other mitochondrial disorders, and in 3243A-->G cell lines in culture,
      indicating that depletion of mtDNA may be a common secondary phenomenon in
      several mitochondrial diseases. Depletion of mtDNA is not always due to mutation
      of a nuclear gene involved in mtDNA maintenance.

PMID- 16950817
TI  - A novel mutation in the mitochondrial tRNA(Ser(AGY)) gene associated with
      mitochondrial myopathy, encephalopathy, and complex I deficiency.
AB  - PURPOSE: To identify molecular defects in a girl with clinical features of MELAS
      (mitochondrial encephalomyopathy and lactic acidosis) and MERRF (ragged-red
      fibres) syndromes. METHODS: The enzyme complex activities of the mitochondrial
      respiratory chain were assayed. Temporal temperature gradient gel electrophoresis
      was used to scan the entire mitochondrial genome for unknown mitochondrial DNA
      (mtDNA) alterations, which were then identified by direct DNA sequencing.
      RESULTS: A novel heteroplasmic mtDNA mutation, G12207A, in the tRNA(Ser(AGY))
      gene was identified in the patient who had a history of developmental delay,
      feeding difficulty, lesions within her basal ganglia, cerebral atrophy, proximal
      muscle weakness, increased blood lactate, liver dysfunction, and fatty
      infiltration of her muscle. Muscle biopsy revealed ragged red fibres and
      pleomorphic mitochondria. Study of skeletal muscle mitochondria revealed complex
      I deficiency associated with mitochondrial proliferation. Real time quantitative
      PCR analysis showed elevated mtDNA content, 2.5 times higher than normal. The
      tRNA(Ser(AGY)) mutation was found in heteroplasmic state (92%) in the patient's
      skeletal muscle. It was not present in her unaffected mother's blood or in 200
      healthy controls. This mutation occurs at the first nucleotide of the 5' end of
      tRNA, which is involved in the formation of the stem region of the amino acid
      acceptor arm. Mutation at this position may affect processing of the precursor
      RNA, the stability and amino acid charging efficiency of the tRNA, and overall
      efficiency of protein translation. CONCLUSION: This case underscores the
      importance of comprehensive mutational analysis of the entire mitochondrial
      genome when a mtDNA defect is strongly suggested.

PMID- 16950818
TI  - Measurement of mRNA of trophoblast-specific genes in cellular and plasma
      components of maternal blood.
AB  - BACKGROUND: Placental mRNA in maternal plasma is suitable for quantitative
      analysis regardless of fetal gender and genetic polymorphism status. METHODS: We
      obtained 155 blood samples from pregnant women to compare human placental
      lactogen (hPL) and beta-subunit of human chorionic gonadotropin (beta hCG) mRNA
      and protein levels between the cellular and plasma components of maternal blood.
      To assess clearance of hPL mRNA expression, we obtained blood samples from nine
      women immediately before and after delivery by caesarean section. mRNA was
      extracted from the cellular and plasma components of all samples, and hPL and
      beta hCG mRNA expression was analysed by reverse transcription-PCR assay.
      RESULTS: The concentration of beta hCG mRNA in the cellular component positively
      correlated with the plasma concentration of beta hCG protein and beta hCG mRNA (p
      = 0.001 for both). The concentration of hPL protein in the plasma correlated with
      the hPL mRNA concentration of the cellular component (p<0.05). For both hPL and
      beta hCG, the mRNA concentration of the cellular component was greater than that
      of the plasma component (22.9-fold higher for hPL and 4.3-fold higher for beta
      hCG). The half life of hPL mRNA clearance was significantly longer for the
      cellular fraction (mean half life = 203.8 min, range 150-3465 min) than for the
      plasma fraction (mean half life = 32.2 min, range 15-385 min) (p = 0.008).
      CONCLUSION: The present findings indicate that the concentration of hPL and beta
      hCG mRNA is significantly higher in the cellular component of maternal blood
      samples than in the plasma component. Cellular mRNA in maternal blood is useful
      for non-invasive evaluation of placental function.

PMID- 16950819
TI  - Novel NHLRC1 mutations and genotype-phenotype correlations in patients with
      Lafora's progressive myoclonic epilepsy.
AB  - BACKGROUND: Lafora's progressive myoclonic epilepsy (Lafora's disease) is an
      autosomal recessive neurodegenerative disorder characterised by the presence of
      polyglucosan intracellular inclusions called Lafora bodies. Mutations in two
      genes, EPM2A and NHLRC1, have been shown to cause the disease. A previous study
      showed mutations in the EPM2A gene in 14 Lafora's disease families and excluded
      the involvement of this gene in five other families who were biopsy proven to
      have the disease. OBJECTIVE: To relate the genetic findings to the clinical
      course of the disease. METHODS: As part of an ongoing mutational study of the
      Lafora's disease genes, five new families with the disease were recruited and the
      genetic analysis was extended to screen the entire coding region of the NHLRC1
      gene. Genotype-phenotype correlations were carried out. RESULTS: Seven NHLRC1
      mutations were identified, including five novel mutations (E91K, D195N, P218S,
      F216_D233del, and V359fs32), in eight families with Lafora's disease. On relating
      the genetic findings to the clinical course of the disease it was shown that
      patients with NHLRC1 mutations had a slower rate of disease progression
      (p<0.0001) and thus appeared to live longer than those with EPM2A mutations. A
      simple DNA based test is described to detect the missense mutation C26S (c.76T-
      >A) in the NHLRC1 gene, which is prevalent among French Canadians. CONCLUSIONS:
      Patients with NHLRC1 mutations have a slower rate of disease progression than
      those with EPM2A mutations.

PMID- 16950821
TI  - Comment on: non-adherence to infectious diseases consultations: are surgeons to
      blame?

PMID- 16950820
TI  - The contribution of germline rearrangements to the spectrum of BRCA2 mutations.
AB  - BACKGROUND: Few germline BRCA2 rearrangements have been described compared with
      the large number of germline rearrangements reported in the BRCA1 gene. However,
      some BRCA2 rearrangements have been reported in families that included at least
      one case of male breast cancer. OBJECTIVE: To estimate the contribution of large
      genomic rearrangements to the spectrum of BRCA2 defects. METHODS: Quantitative
      multiplex PCR of short fluorescent fragments (QMPSF) was used to screen the BRCA2
      gene for germline rearrangements in highly selected families. QMPSF was
      previously used to detect heterozygous deletions/duplications in many genes
      including BRCA1 and BRCA2. RESULTS: We selected a subgroup of 194 high risk
      families with four or more breast cancers with an average age at diagnosis of <
      or = 50 years, who were recruited through 14 genetic counselling centres in
      France and one centre in Switzerland. BRCA2 mutations were detected in 18.6% (36
      index cases) and BRCA1 mutations in 12.4% (24 index cases) of these families. Of
      the 134 BRCA1/2 negative index cases in this subgroup, 120 were screened for
      large rearrangements of BRCA2 using QMPSF. Novel and distinct BRCA2 deletions
      were detected in three families and their boundaries were determined. We found
      that genomic rearrangements represent 7.7% (95% confidence interval 0% to 16%) of
      the BRCA2 mutation spectrum. CONCLUSION: The molecular diagnosis of breast cancer
      predisposition should include screening for BRCA2 rearrangements, at least in
      families with a high probability of BRCA2 defects.

PMID- 16950822
TI  - Prior use of carbapenems may be a significant risk factor for extended-spectrum
      beta-lactamase-producing Escherichia coli or Klebsiella spp. in patients with
      bacteraemia.
AB  - BACKGROUND: The increasing prevalence of extended-spectrum beta-lactamase (ESBL)
      producing Enterobacteriaceae will probably trigger a rise in the use of
      carbapenems. The effect of these antibiotics on the risk of involvement of ESBL
      producing organisms in serious infections is unclear. METHODS: Retrospective
      analysis of 2172 episodes of healthcare-associated bacteraemia diagnosed during a
      3 year period in a teaching hospital. Putative risk factors included
      demographics, co-morbidities, previous isolation of an ESBL-producing organism
      and exposure to antibiotics. Univariate and multivariate analysis of the
      association of risk factors with ESBL-producing organisms was performed in the
      entire series of bacteraemic episodes and in those due to Escherichia coli or
      Klebsiella spp. RESULTS: In the entire series, prior isolation of an ESBL
      producing organism [odds ratio (OR) 5.9 (3.02, 11.5)]; an ultimately/finally
      fatal co-morbidity [OR 2.8 (1.55, 4.95)]; renal transplantation [OR 4.3 (1.96,
      9.63)]; a urinary source [OR 4.2 (2.22, 7.84)]; shock [OR 2.4 (1.35, 4.1)] and
      previous use of cephalosporins [OR 2.6 (1.54, 4.51)], carbapenems [OR 2.5 (1.24,
      5.05)] and glycopeptides [OR 0.4 (0.13, 0.93)] were significantly associated with
      ESBL-producing E. coli or Klebsiella spp. by multivariate analysis. Prior
      isolation of an ESBL-producing organism, an ultimately/finally fatal co
      morbidity, renal transplantation, and previous use of cephalosporins and
      carbapenems were also significant in the analysis restricted to episodes due to
      E. coli or Klebsiella spp. CONCLUSIONS: In patients with healthcare-associated
      bacteraemia, prior use of carbapenems may be only second to cephalosporins as the
      most significant antibiotic exposure associated with the involvement of ESBL
      producing organisms.

PMID- 16950823
TI  - Subclinical hypothyroidism in HIV-infected subjects.
AB  - OBJECTIVES: The correlation between subclinical hypothyroidism [thyroid
      stimulating hormone (TSH)>4 mIU/L with normal free triiodothyroxine and free
      thyroxine levels], HIV infection and HAART is still unclear. PATIENTS AND
      METHODS: To evaluate the predictive factors of subclinical hypothyroidism in an
      HIV-infected population, we identified three groups of subjects: G1, subjects on
      stable highly active antiretroviral therapy (HAART) (for at least 1 year) at
      baseline and at month 24 (n=97); G2, subjects naive at both baseline and month 24
      (n=47); G3, subjects starting HAART at baseline (n=46). RESULTS: The three groups
      were comparable with respect to age, gender, body weight and prevalence of HCV
      infection. At baseline, subclinical hypothyroidism was detected in 14 subjects in
      G1 (14.4%), 5 in G2 (10.6%) and 4 in G3 (8.7%) (P=0.18) and these were excluded
      from the analysis. At month 24, 15 subjects had developed subclinical
      hypothyroidism: 4 in G1 (4.8%), 3 in G2 (7.1%) and 8 in G3 (19.0%). In the
      multivariable analysis, the higher increase in total cholesterol was predictive
      of subclinical hypothyroidism (RR: 1.53 for each additional 10 mg/dL, 95% CI 1.23
      1.90; P<0.01); other variables, which were statistically significant in the
      univariate analysis, such as G3 group, body weight and higher increase in CD4+
      cell count and in triglyceride serum levels were not confirmed to be associated
      with TSH alterations. CONCLUSIONS: The occurrence of subclinical hypothyroidism
      in HIV-positive patients seems to be related to the increase in total cholesterol
      serum levels occurring after HAART initiation. Thyroid function should be
      monitored in all HIV-infected subjects, especially in those starting HAART.

PMID- 16950824
TI  - Effects of weak acids, UV and proton motive force inhibitors on pyrazinamide
      activity against Mycobacterium tuberculosis in vitro.
AB  - BACKGROUND: Pyrazinamide is a paradoxical frontline tuberculosis drug
      characterized by high sterilizing in vivo activity but poor in vitro activity.
      Pyrazinamide is thought to act by the entrapment of pyrazinoic acid in the
      bacterial cell, leading to acidification and membrane damage. Consequently, the
      effects of weak acids and molecules affecting membranes added to pyrazinamide
      were studied. OBJECTIVES: To examine the effects of weak acids, UV, oxidative
      stress and additional energy inhibitors on pyrazinamide activity in vitro against
      Mycobacterium tuberculosis as well as the effect of pyrazinamide on Escherichia
      coli ampicillin persisters. METHODS: Drug exposure experiments followed by cfu
      counts were performed to determine the effects of the above various factors on
      pyrazinamide activity in vitro against M. tuberculosis. RESULTS: Some weak acids
      such as benzoic acid, sorbic acid and propyl hydroxybenzoic acid could enhance
      the activity of pyrazinamide in vitro against old tubercle bacilli but not young
      bacilli whereas other weak acids such as salicylic acid and lactic acid did not
      appear to enhance pyrazinamide activity. While energy inhibitors carbonylcyanide
      m-chlorophenylhydrazone and dinitrophenol enhanced pyrazinamide activity for old
      tubercle bacilli but not young bacilli, valinomycin and KCN increased
      pyrazinamide activity for both young and old bacilli. Oxidative stresses due to
      H2O2 and menadione did not have a significant effect on pyrazinamide activity.
      UV, which presumably damages the membrane, enhanced the activity of pyrazinamide.
      Pyrazinamide, which otherwise has no activity against actively growing E. coli
      bacteria, could kill non-growing starved E. coli and also ampicillin-tolerant
      persisters. CONCLUSIONS: Some weak acids, UV and various energy inhibitors were
      found to enhance the activity of pyrazinamide in vitro against M. tuberculosis.
      Pyrazinamide shows preferential activity against both M. tuberculosis and E. coli
      persisters over the growing forms.

PMID- 16950825
TI  - The CryoLoop facilitates re-vitrification of embryos at four successive stages of
      development without impairing embryo growth.
AB  - BACKGROUND: Vitrification has been shown to be an effective method of
      cryopreservation, but little is known about re-vitrification of embryos. This
      study investigated the effect of re-vitrification on mouse embryo preimplantation
      development and viability post-transfer. METHODS: Mouse embryos at the 1-cell
      stage were vitrified using the CryoLoop technique. Embryos were warmed and then
      re-vitrified successively at the 2-, 8-cell and blastocyst stages. The effects of
      multiple rounds of vitrification on development, differentiation and viability
      were assessed and compared with non-vitrified embryos. RESULTS: Development to
      the 8-cell stage on day 3 and blastocyst on day 5 were not affected by re
      vitrification. However, better hatching rates were observed in the non-vitrified
      control group. Total cell number and the number of cells allocated to the inner
      cell mass (ICM) were not different between treatments. The percentage of ICM
      development was also not different between treatments. Implantation rate and
      fetal weights were the same between treatments. However, overall there were fewer
      fetuses per embryo transferred in the re-vitrified group. CONCLUSION: Re
      vitrification of mouse embryos has minimal effect on preimplantation embryo
      development or implantation potential.

PMID- 16950826
TI  - Surgical routes and complications of hysterectomy for benign disorders: a
      prospective observational study in French university hospitals.
AB  - BACKGROUND: Despite the advantages of the vaginal and laparoscopic approaches,
      most hysterectomies carried out involve laparotomy. The objective of this
      prospective observational multicentre study was to examine the routes and
      complications of hysterectomy for benign disorders. METHODS: Of the 15 university
      hospitals belonging to Collegiale de Gynecologie-Obstetrique de Paris-Ile de
      France, 12 participated in this study that took place between June and December
      2004. We analysed the characteristics of the patients, the indications for
      hysterectomy and intra- and post-operative complications (and their determinants)
      according to the surgical approach. RESULTS: In total, 634 women underwent
      hysterectomy for benign disorders during the study period. The patients' mean age
      (+/-SD), BMI, parity and previous Caesarean sections were 51.4 +/- 10.3 years, 25
      +/- 5.7 kg/m(2), 2 +/- 1.6 children and 0.2 +/- 0.6, respectively. Hysterectomy
      was performed by the laparoscopic, laparoscopically assisted vaginal hysterectomy
      (LAVH), laparotomic and vaginal routes in 19.1, 8.2, 24.4 and 48.3% of cases,
      respectively. The operating time was shorter with the vaginal route than with
      laparoscopy, laparotomy and LAVH (P < 0.0001). Intra- and post-operative
      complications were significantly more frequent in the laparotomic group (18%)
      compared with the vaginal group (8.2%), the laparoscopic group (5.8%) and the
      LAVH group (8.2%) (P < 0.0001). In a multivariate logistic regression model,
      obesity [odds ratio (OR): 2.84, 95% confidence interval (CI): 1.53-5.27, P =
      0.001], history of pelvic surgery (OR: 2.47, 95% CI: 1.39-4.39, P = 0.002) and
      history of Caesarean section (OR: 2.04, 95% CI: 1.01-4.1, P = 0.046) were
      significantly associated with intra- and post-operative complications.
      Laparoconversion was necessary in 36 cases (7.5%) overall and was more frequent
      with laparoscopy and LAVH than with the vaginal route (P < 0.0001). CONCLUSIONS:
      This study confirms that the vaginal route is increasingly used for hysterectomy
      in France and that it is the route of choice for benign disorders.

PMID- 16950827
TI  - Nerve fibres in peritoneal endometriosis.
AB  - BACKGROUND: Endometriosis is a gynaecological disease that can be associated with
      severe pelvic pain; however, the mechanisms by which pain is generated remain
      unknown. METHODS: Peritoneal endometriotic lesions and normal peritoneum were
      prepared from women with and without endometriosis (n = 40 and 36, respectively).
      Specimens were also prepared from endosalpingiosis lesions (n = 9). These
      sections were stained immunohistochemically with antibodies against protein gene
      product 9.5, neurofilament (NF), nerve growth factor (NGF), NGF receptor p75
      (NGFRp75), substance P (SP), calcitonin gene-related peptide (CGRP),
      acetylcholine (ACh) and tyrosine hydroxylase (TH) to demonstrate myelinated,
      unmyelinated, sensory, cholinergic and adrenergic nerve fibres. RESULTS: There
      were significantly more nerve fibres identified in peritoneal endometriotic
      lesions than in normal peritoneum (P < 0.001) or endosalpingiosis lesions (P <
      0.001). These nerve fibres were SP, CGRP, ACh or TH immunoreactive. Many of these
      markers were co-localized. There was an intense NGF immunoreactivity near
      endometriotic glands, and NGFRp75 immunoreactive nerve fibres were present near
      endometriotic glands and blood vessels in the peritoneal endometriotic lesions.
      CONCLUSIONS: Peritoneal endometriotic lesions were innervated by sensory Adelta,
      sensory C, cholinergic and adrenergic nerve fibres. These nerve fibres may play
      an important role in the mechanisms of pain generation in this condition.

PMID- 16950828
TI  - Amino acid, ammonia and urea concentrations in human pre-ovulatory ovarian
      follicular fluid.
AB  - BACKGROUND: This study aimed to determine amino acid (AA), ammonia and urea
      concentrations in human ovarian follicular fluid and to compare these
      concentrations with those in the circulation. METHODS: Samples of pre-ovulatory
      follicular fluid and peripheral venous blood were obtained from 14 IVF patients.
      High-performance liquid chromatography (HPLC) measurements of 25 AAs were the
      main outcome measures. RESULTS: There was a significant gradient of most AAs from
      plasma to follicular fluid, with the exception of glutamate, which demonstrated a
      three-fold increase in follicular fluid concentration (70.0 +/- 3.80 microM)
      compared with plasma (23.18 +/- 2.20 microM; P < 0.001). The plasma-to-follicular
      fluid concentration difference for glutamine (81.83 +/- 9.2 microM) was greatest
      among all AAs. Among essential AAs, this difference was greatest for the branched
      chain AAs, isoleucine, leucine and valine. Ammonia concentrations in follicular
      fluid and blood were 38.87 +/- 2.23 and 22.11 +/- 1.96 microM, respectively (P <
      0.001). Urea concentration in follicular fluid was 3.37 +/- 0.18 mM, a value not
      significantly different from plasma concentration (3.36 +/- 0.22 mM; P = 0.911).
      CONCLUSIONS: These plasma-follicular fluid differences may reflect both the
      utilization of AAs and the transport characteristics of the follicular cells.
      There is accumulation of glutamate and ammonia in pre-ovulatory follicular fluid.
      The data for urea are consistent with transport by passive diffusion, with no
      evidence of an active urea cycle in the cells of the follicle.

PMID- 16950829
TI  - Co-occurrence of the multicopper oxidases tyrosinase and laccase in lichens in
      sub-order peltigerineae.
AB  - BACKGROUND AND AIMS: Following previous findings of high extracellular redox
      activity in lichens and the presence of laccases in lichen cell walls, the work
      presented here additionally demonstrates the presence of tyrosinases. Tests were
      made for the presence of tyrosinases in 40 species of lichens, and from selected
      species their cellular location and molecular weights were determined. The
      effects of stress and inhibitors on enzyme activity were also studied. METHODS:
      Tyrosinase and laccase activities were assayed spectrophotometrically using a
      variety of substrates. The molecular mass of the enzymes was estimated using
      polyacrylamide gel electrophoresis. KEY RESULTS: Extracellular tyrosinase and
      laccase activity was measured in 40 species of lichens from different taxonomic
      groupings and contrasting habitats. Out of 20 species tested from the sub-order
      Peltigerineae, all displayed significant tyrosinase and laccase activity, while
      activity was low or absent in other species tested. Representatives from both
      groups of lichens displayed low peroxidase activities. Identification of the
      enzymes as tyrosinases was confirmed by the ability of lichen thalli or leachates
      derived by shaking lichens in distilled water to metabolize substrates such as L
      dihydroxyphenylalanine (DOPA), tyrosine and epinephrine readily in the absence of
      hydrogen peroxide, the sensitivity of the enzymes to the inhibitors cyanide,
      azide and hexylresorcinol, activation by SDS and having typical tyrosinase
      molecular masses of approx. 60 kDa. Comparing different species within the
      Peltigerineae showed that the activities of tyrosinases and laccase were
      correlated to each other. Desiccation and wounding stimulated laccase activity,
      while only wounding stimulated tyrosinase activity. CONCLUSIONS: Cell walls of
      lichens in sub-order Peltigerineae have much higher activities and a greater
      diversity of cell wall redox enzymes compared with other lichens. Possible roles
      of tyrosinases include melanization, removal of toxic phenols or quinones, and
      production of herbivore deterrents.

PMID- 16950830
TI  - Genetic structure of Galitzkya macrocarpa and G. potaninii, two closely related
      endemics of central Asian mountain ranges.
AB  - BACKGROUND AND AIMS Habitats in mountains are often isolated. Plants growing in
      these sites face severe dispersal limitations, but also difficulties for
      recruitment. The focus was laid on the magnitude of genetic differences among
      populations but also on the size of potentially occurring clones. METHODS: RAPD
      fingerprints were obtained from 23 populations in southern Mongolia. Sampling
      covered the entire distribution range of Galitzkya macrocarpa; samples of G.
      potaninii represented only the Mongolian part of its mainly northern Chinese
      range. KEY RESULTS: The Mongolian endemic G. macrocarpa showed moderately strong
      population differentiation (Phi ST = 0.251), and limited evidence for isolation
      by distance. Local genetic diversity was not positively correlated to habitat
      size, and not reduced in peripheral populations. Clonal growth is possible, but
      most plants originate from sexual reproduction. In contrast, populations of G.
      potaninii were highly differentiated (Phi ST = 0.550); and the most remote
      outposts had reduced genetic diversity. In these areas, isolation is expected to
      date back to glacial times. CONCLUSIONS: Effects of natural fragmentation differ
      among species. Both are rare, but G. macrocarpa appears to be able to maintain
      genetic diversity over its range. Clonal growth is an option in its mixed
      reproduction strategy and allows survival under harsh conditions. In contrast,
      genetic structure in G. potaninii gives reason for concern, and further studies
      on population dynamics are needed.

PMID- 16950831
TI  - Non-viral delivery of nuclear factor-kappaB decoy ameliorates murine inflammatory
      bowel disease and restores tissue homeostasis.
AB  - BACKGROUND: Nuclear factor-kappaB (NF-kappaB) is a key transcriptional regulator
      of inflammatory bowel disease (IBD). AIM: To investigate the therapeutic
      potential of a locally administered "non-viral" nuclear factor-kappaB decoy
      (NFkappaBD) in multiple experimental models of IBD. METHODS: A fully
      phosphorothioated decoy oligonucleotide with improved stability that specifically
      binds NF-kappaB and blocks inflammatory mediators regulated by this transcription
      factor without the help of viral envelope-assisted delivery was developed. The
      therapeutic effects of NFkappaBD were studied in the trinitrobenzene sulphonic
      acid, oxazolone and dextran sodium sulphate induced colitis models. RESULTS:
      Intracolonic administration of NFkappaBD results in the delivery of NFkappaBD to
      inflammatory cells and a reduction of NF-kappaB heterodimers. In the T helper
      cell 1-driven trinitrobenzene sulphonic acid-induced colitis model, mice
      receiving NFkappaBD treatment exhibit a dose-dependent reduction in disease
      severity and a more rapid recovery to normal body weight, similar to a clinically
      relevant dose of budesonide. Clinical efficacy was corroborated by considerable
      reductions in colitis pathology and tissue levels of several pro-inflammatory
      markers, including tumour necrosis factor alpha, interleukin 6, interleukin 1beta
      and monocyte chemotactic protein 1. NFkappaBD also mitigates disease activity in
      the T helper cell 2-like oxazolone colitis and epithelial injury-related acute
      dextran sodium sulphate colitis models. Interestingly, restoration of tissue
      homeostasis is observed in NFkappaBD-treated animals with the rapid re-emergence
      of functional goblet cells and a return to normal patterns of cell proliferation
      in the mucosal epithelium and smooth muscle cell layers. CONCLUSIONS: These data
      support the potential use of "naked" NFkappaBD as a cross-functional therapeutic
      in IBD, and show for the first time that it can facilitate the restoration of
      colon homeostasis and function.

PMID- 16950832
TI  - The role of the nuclear receptor constitutive androstane receptor in the
      pathogenesis of non-alcoholic steatohepatitis.
AB  - BACKGROUND: Non-alcoholic fatty liver disease is a common liver injury, but the
      pathophysiological mechanisms leading to the development of non-alcoholic
      steatohepatitis (NASH) remain unclear. The pathological roles of the nuclear
      receptor constitutive androstane receptor (CAR), a key regulator of drug
      metabolising enzymes, in the development of NASH were investigated. METHODS AND
      RESULTS: CAR(+/+) and CAR(-/-) mice were given a methionine and choline-deficient
      (MCD) diet to establish a dietary model of NASH. Increases in serum alanine
      aminotransferase (ALT) and in infiltration of inflammatory cells were dominant in
      CAR(+/+) mice at 8 weeks. There was no significant difference in the lipid
      concentration of the liver - namely, the first hit between CAR(+/+) and CAR(-/-)
      mice. The index of lipid peroxidation increased in liver of the CAR(+/+) mice, as
      demonstrated by 8-iso-prostaglandin F2alpha (F2-isoprostanes). Western blotting
      analysis showed that nuclear translocation of CAR occurred in CAR(+/+) mice fed
      the MCD diet. As a result, the CAR activation caused the lipid peroxidation -
      namely, the second hit. The expressions of cytochrome P450 (CYP)2B10, 2C29, 3A11
      all increased considerably in the CAR(+/+) mice. Furthermore, alpha smooth muscle
      actin immunohistochemistry and Sirius red staining showed an increase in the
      degree of fibrosis in CAR(+/+) mice fed the MCD diet at 16 weeks. The mRNA
      expressions of collagen alpha1(1) and the tissue inhibitor of metalloproteinase-1
      were found to be elevated in CAR(+/+) mice. CONCLUSION: CAR caused the worsening
      of the hepatic injury and fibrosis in the dietary model of NASH. Our results
      suggest that the CAR nuclear receptor may thus play a critical role in the
      pathogenesis of NASH.

PMID- 16950833
TI  - Oral proteases: a new approach to managing coeliac disease.
AB  - A life-long but constraining gluten-free diet is the only treatment currently
      available for coeliac disease. The human gastrointestinal tract does not possess
      the enzymatic equipment to efficiently cleave the gluten-derived proline-rich
      peptides driving the abnormal immune intestinal response in patients with coeliac
      disease. Oral therapy by exogenous prolylendopeptidases able to digest ingested
      gluten was therefore propounded as an alternative treatment to the diet. The
      feasibility of this approach is discussed by reviewing recent data on the
      intestinal transport of gliadin peptides, properties of available enzymes and
      preliminary clinical assays. Development of new enzymes or enzymatic cocktails
      offers potentially more potent therapeutic tools that, however, need meticulous
      evaluation based on clinical, biological and histological criteria.

PMID- 16950834
TI  - Post-infective and chronic fatigue syndromes precipitated by viral and non-viral
      pathogens: prospective cohort study.
AB  - OBJECTIVE: To delineate the risk factors, symptom patterns, and longitudinal
      course of prolonged illnesses after a variety of acute infections. DESIGN:
      Prospective cohort study following patients from the time of acute infection with
      Epstein-Barr virus (glandular fever), Coxiella burnetii (Q fever), or Ross River
      virus (epidemic polyarthritis). SETTING: The region surrounding the township of
      Dubbo in rural Australia, encompassing a 200 km geographical radius and 104,400
      residents. PARTICIPANTS: 253 patients enrolled and followed at regular intervals
      over 12 months by self report, structured interview, and clinical assessment.
      OUTCOME MEASURES: Detailed medical, psychiatric, and laboratory evaluations at
      six months to apply diagnostic criteria for chronic fatigue syndrome. Premorbid
      and intercurrent illness characteristics recorded to define risk factors for
      chronic fatigue syndrome. Self reported illness phenotypes compared between
      infective groups. RESULTS: Prolonged illness characterised by disabling fatigue,
      musculoskeletal pain, neurocognitive difficulties, and mood disturbance was
      evident in 29 (12%) of 253 participants at six months, of whom 28 (11%) met the
      diagnostic criteria for chronic fatigue syndrome. This post-infective fatigue
      syndrome phenotype was stereotyped and occurred at a similar incidence after each
      infection. The syndrome was predicted largely by the severity of the acute
      illness rather than by demographic, psychological, or microbiological factors.
      CONCLUSIONS: A relatively uniform post-infective fatigue syndrome persists in a
      significant minority of patients for six months or more after clinical infection
      with several different viral and non-viral micro-organisms. Post-infective
      fatigue syndrome is a valid illness model for investigating one
      pathophysiological pathway to chronic fatigue syndrome.

PMID- 16950835
TI  - Angry breathing: A prospective study of hostility and lung function in the
      Normative Aging Study.
AB  - BACKGROUND: Hostility and anger are risk factors for, or co-occur with, many
      health problems of older adults such as cardiovascular diseases, all-cause
      mortality, and asthma. Evidence that negative emotions are associated with
      chronic airways obstruction suggests a possible role for hostility in the
      maintenance and decline of pulmonary function. This study tests the hypothesis
      that hostility contributes to a faster rate of decline in lung function in older
      adults. METHODS: A prospective examination was undertaken of the effect of
      hostility on change in lung function over time. Data are from the VA Normative
      Aging Study, an ongoing cohort of older men. Hostility was measured in 1986 in
      670 men who also had an average of three pulmonary function examinations obtained
      over an average of 8.2 years of follow up. Hostility was ascertained using the 50
      item MMPI based Cook-Medley Hostility Scale. Pulmonary function was assessed
      using spirometric tests to obtain measures of forced expiratory volume in 1
      second (FEV1) and forced vital capacity (FVC). RESULTS: Baseline pulmonary
      function differed between high and medium/low hostility groups (mean (SE) percent
      predicted FEV(1) 88.9 (18.5) v 95.3 (16.9) and FVC 92.5 (16.5) v 98.9 (15.9),
      respectively; p < 0.01 for both). This overall association between higher
      hostility and reduced lung function remained significant after adjusting for
      smoking and education, although the effect size was attenuated for both FEV1 and
      FVC. Higher hostility was associated with a more rapid decline in lung function,
      and this effect was unchanged and remained significant for FEV1)in multivariate
      models but was attenuated for FVC. Each standard deviation increase in hostility
      was associated with a loss in FEV1 of approximately 9 ml/year. CONCLUSIONS: This
      study is one of the first to show prospectively that hostility is associated with
      poorer pulmonary function and more rapid rates of decline among older men.

PMID- 16950836
TI  - Time trends in allergic disorders in the UK.
AB  - BACKGROUND: Allergic disorders are common in the UK. This study reviews recent UK
      time trends in the prevalence, morbidity and mortality for allergic disorders,
      excluding asthma. METHODS: A trend analysis was performed over recent decades of
      national, representative or repeat surveys, primary care consultations,
      prescriptions, hospital admissions, and mortality. RESULTS: Serial surveys showed
      that the prevalence of diagnosed allergic rhinitis and eczema in children have
      both trebled over the last three decades. While these long term trends were
      paralleled by the prevalence of disease symptoms, more recent symptom prevalence
      data suggest a decline. Similarly, GP consultation rates rose by 260% for hay
      fever and by 150% for eczema overall during the period 1971-91, but rates have
      stabilised over the past decade. Hospital admissions for eczema have been stable
      since 1995, and hospital admissions for allergic rhinitis have fallen to about
      40% of their 1990 levels. Since 1990, admissions for anaphylaxis have increased
      by 700%, for food allergy by 500%, for urticaria by 100%, and for angio-oedema by
      40%. Prescriptions issued for all types of allergy have increased since 1991.
      CONCLUSIONS: The prevalence and healthcare usage for eczema and hay fever have
      increased substantially over recent decades, but may now be stabilising or even
      falling. In contrast, admissions for some systemic allergic diseases have risen
      sharply in the last decade which may indicate a rising incidence of these
      conditions. Although changes in treatment and other healthcare factors may have
      contributed to these trends, there may also be a change in the aetiology of
      allergic disease in the UK.

PMID- 16950837
TI  - Diffraction-based density restraints for membrane and membrane-peptide molecular
      dynamics simulations.
AB  - We have recently shown that current molecular dynamics (MD) atomic force fields
      are not yet able to produce lipid bilayer structures that agree with
      experimentally-determined structures within experimental errors. Because of the
      many advantages offered by experimentally validated simulations, we have
      developed a novel restraint method for membrane MD simulations that uses
      experimental diffraction data. The restraints, introduced into the MD force
      field, act upon specified groups of atoms to restrain their mean positions and
      widths to values determined experimentally. The method was first tested using a
      simple liquid argon system, and then applied to a neat
      dioleoylphosphatidylcholine (DOPC) bilayer at 66% relative humidity and to the
      same bilayer containing the peptide melittin. Application of experiment-based
      restraints to the transbilayer double-bond and water distributions of neat DOPC
      bilayers led to distributions that agreed with the experimental values. Based
      upon the experimental structure, the restraints improved the simulated structure
      in some regions while introducing larger differences in others, as might be
      expected from imperfect force fields. For the DOPC-melittin system, the
      experimental transbilayer distribution of melittin was used as a restraint. The
      addition of the peptide caused perturbations of the simulated bilayer structure,
      but which were larger than observed experimentally. The melittin distribution of
      the simulation could be fit accurately to a Gaussian with parameters close to the
      observed ones, indicating that the restraints can be used to produce an ensemble
      of membrane-bound peptide conformations that are consistent with experiments.
      Such ensembles pave the way for understanding peptide-bilayer interactions at the
      atomic level.

PMID- 16950838
TI  - Spatially resolved fluorescence correlation spectroscopy using a spinning disk
      confocal microscope.
AB  - We develop an extension of fluorescence correlation spectroscopy (FCS) using a
      spinning disk confocal microscope. This approach can spatially map diffusion
      coefficients or flow velocities at up to approximately 10(5) independent
      locations simultaneously. Commercially available cameras with frame rates of 1000
      Hz allow FCS measurements of systems with diffusion coefficients D~10(-7) cm(2)/s
      or smaller. This speed is adequate to measure small microspheres (200-nm
      diameter) diffusing in water, or hindered diffusion of macromolecules in complex
      media (e.g., tumors, cell nuclei, or the extracellular matrix). There have been a
      number of recent extensions to FCS based on laser scanning microscopy. Spinning
      disk confocal microscopy, however, has the potential for significantly higher
      speed at high spatial resolution. We show how to account for a pixel size effect
      encountered with spinning disk confocal FCS that is not present in standard or
      scanning FCS, and we introduce a new method to correct for photobleaching.
      Finally, we apply spinning disk confocal FCS to microspheres diffusing in Type I
      collagen, which show complex spatially varying diffusion caused by hydrodynamic
      and steric interactions with the collagen matrix.

PMID- 16950839
TI  - Low-temperature fluorescence from single chlorosomes, photosynthetic antenna
      complexes of green filamentous and sulfur bacteria.
AB  - Fluorescence spectra of single chlorosomes isolated from a green filamentous
      bacterium (Chloroflexus (Cfl.) aurantiacus) and a green sulfur bacterium
      (Chlorobium (Cb.) tepidum) were measured by using a confocal laser microscope at
      13 K. Chlorosomes were frozen either in a liquid solution (floating chlorosome)
      or on a quartz plate after being adsorbed (adsorbed chlorosome). Fluorescence
      peak wavelengths were shorter for the adsorbed single chlorosomes than for the
      floating ones. Single floating Cfl. chlorosomes showed a distribution of
      fluorescence peak positions having a center at 759.0 nm with a full width at half
      maximum of 6.3 nm. Single floating Cb. chlorosomes showed a 782.7 nm center with
      a full width at half-maximum of 3.4 nm. The distribution shifted to the blue and
      became wider with increasing temperature, especially in Cb. chlorosomes,
      suggesting a large excitonic density of states just above the lowest level.
      Energy transfer from BChl-c aggregates to BChl-a molecules in the baseplate
      proteins was observed in the floating chlorosomes but not in the adsorbed ones. A
      positive correlation was found between the peak wavelength of BChl-c fluorescence
      and the intensity of BChl-a fluorescence in single Cfl. chlorosomes. The results
      suggest that the BChl-c aggregates with longer wavelengths of the fluorescence
      peaks have a more efficient Forster-type energy transfer to the baseplate BChl-a.

PMID- 16950840
TI  - Dynamics and diffusion in photosynthetic membranes from rhodospirillum
      photometricum.
AB  - Photosynthetic organisms drive their metabolism by converting light energy into
      an electrochemical gradient with high efficiency. This conversion depends on the
      diffusion of quinones within the membrane. In purple photosynthetic bacteria,
      quinones reduced by the reaction center (RC) diffuse to the cytochrome bc(1)
      complex and then return once reoxidized to the RC. In Rhodospirillum
      photometricum the RC-containing core complexes are found in a disordered
      molecular environment, with fixed light-harvesting complex/core complex ratio but
      without a fixed architecture, whereas additional light-harvesting complexes
      synthesized under low-light conditions pack into large paracrystalline antenna
      domains. Here, we have analyzed, using time-lapse atomic force microscopy, the
      dynamics of the protein complexes in the different membrane domains and find that
      the disordered regions are dynamic whereas ordered antennae domains are static.
      Based on our observations we propose, and analyze using Monte Carlo simulations,
      a model for quinone diffusion in photosynthetic membranes. We show that the
      formation of large static antennae domains may represent a strategy for
      increasing electron transfer rates between distant complexes within the membrane
      and thus be important for photosynthetic efficiency.

PMID- 16950841
TI  - Microenvironment and effect of energy depletion in the nucleus analyzed by
      mobility of multiple oligomeric EGFPs.
AB  - Four different tandem EGFPs were constructed to elucidate the nuclear
      microenvironment by quantifying its diffusional properties in both aqueous
      solution and the nuclei of living cells. Diffusion of tandem EGFP was dependent
      on the length of the protein as a rod-like molecule or molecular ruler in
      solution. On the other hand, we found two kinds of mobility, fast diffusional
      mobility and much slower diffusional mobility depending on cellular compartments
      in living cells. Diffusion in the cytoplasm and the nucleoplasm was mainly
      measured as fast diffusional mobility. In contrast, diffusion in the nucleolus
      was complex and mainly much slower diffusional mobility, although both the fast
      and the slow diffusional mobilities were dependent on the protein length.
      Interestingly, we found that diffusion in the nucleolus was clearly changed by
      energy depletion, even though the diffusion in the cytoplasm and the nucleoplasm
      was not changed. Our results suggest that the nucleolar microenvironment is
      sensitive to energy depletion and very different from the nucleoplasm.

PMID- 16950842
TI  - Molecular dynamics simulation of dextran extension by constant force in single
      molecule AFM.
AB  - The extension of 1-6 polysaccharides has been studied in a series of recent
      single molecule AFM experiments. For dextran, a key finding was the existence of
      a plateau in the force-extension curve at forces between 700 and 1000 pN. We
      studied the extension of the dextran 10-mer under constant force using atomistic
      simulation with various force fields. All the force fields reproduce the
      experimental plateau on the force-extension curve. With AMBER94 and AMBER
      GLYCAM04 force fields the plateau can be explained by a transition of the
      glucopyranose rings in the dextran monomers from the chair ((4)C(1)) to the
      inverted chair ((1)C(4)) conformation while other processes occur at smaller
      (rotation around C5-C6 bond) or higher (chairs to boat transitions) forces. The
      CHARMM force field provides a different picture which associates the occurrence
      of the plateau to chair-boat transitions of the glucopyranose rings.

PMID- 16950843
TI  - Sonoporation from jetting cavitation bubbles.
AB  - The fluid dynamic interaction of cavitation bubbles with adherent cells on a
      substrate is experimentally investigated. We find that the nonspherical collapse
      of bubbles near to the boundary is responsible for cell detachment. High-speed
      photography reveals that a wall bounded flow leads to the detachment of cells.
      Cells at the edge of the circular area of detachment are found to be permanently
      porated, whereas cells at some distance from the detachment area undergo viable
      cell membrane poration (sonoporation). The wall flow field leading to cell
      detachment is modeled with a self-similar solution for a wall jet, together with
      a kinetic ansatz of adhesive bond rupture. The self-similar solution for the
      delta-type wall jet compares very well with the full solution of the Navier
      Stokes equation for a jet of finite thickness. Apart from annular sites of
      sonoporation we also find more homogenous patterns of molecule delivery with no
      cell detachment.

PMID- 16950844
TI  - Dielectrophoresis as a tool to characterize and differentiate isogenic mutants of
      Escherichia coli.
AB  - In this study we report on an experimental method based on dielectrophoretic
      analysis to identify changes in four Escherichia coli isogenic strains that
      differed exclusively in one mutant allele. The dielectrophoretic properties of
      wild-type cells were compared to those of hns, hha, and hha hns mutant
      derivatives. The hns and hha genes code respectively for the global regulators
      Hha and H-NS. The Hha and H-NS proteins modulate gene expression in Escherichia
      coli and other Gram negative bacteria. Mutations in either hha or hns genes
      result in a pleiotropic phenotype. A two-shell prolate ellipsoidal model has been
      used to fit the experimental data, obtained from dielectrophoresis measurements,
      and to study the differences in the dielectric properties of the bacterial
      strains. The experimental results show that the mutant genotype can be predicted
      from the dielectrophoretic analysis of the corresponding cultures, opening the
      way to the development of microdevices for specific identification. Therefore,
      this study shows that dielectrophoresis can be a valuable tool to study bacterial
      populations which, although apparently homogeneous, may present phenotypic
      variability.

PMID- 16950845
TI  - Folding of proteins with diverse folds.
AB  - Using parallel tempering simulations with high statistics, we investigate the
      folding and thermodynamic properties of three small proteins with distinct native
      folds: the all-helical 1RIJ, the all-sheet beta3s, and BBA5, which has a mixed
      helix-sheet fold. In all three cases, simulations with our energy function find
      the native structures as global minima in free energy at experimentally relevant
      temperatures. However, the folding process strongly differs for the three
      molecules, indicating that the folding mechanism is correlated with the form of
      the native structure.

PMID- 16950846
TI  - Filament compliance effects can explain tension overshoots during force
      development.
AB  - Spatially explicit stochastic simulations of myosin S1 heads attaching to a
      single actin filament were used to investigate the process of force development
      in contracting muscle. Filament compliance effects were incorporated by adjusting
      the spacing between adjacent actin binding sites and adjacent myosin heads in
      response to cross-bridge attachment/detachment events. Appropriate model
      parameters were determined by multi-dimensional optimization and used to simulate
      force development records corresponding to different levels of Ca(2+) activation.
      Simulations in which the spacing between both adjacent actin binding sites and
      adjacent myosin S1 heads changed by approximately 0.06 nm after cross-bridge
      attachment/detachment events 1), exhibited tension overshoots with a Ca(2+)
      dependence similar to that measured experimentally and 2), mimicked the observed
      k(tr)-relative tension relationship without invoking a Ca(2+)-dependent increase
      in the rate of cross-bridge state transitions. Tension did not overshoot its
      steady-state value in control simulations modeling rigid thick and thin filaments
      with otherwise identical parameters. These results underline the importance of
      filament geometry and actin binding site availability in quantitative theories of
      muscle contraction.

PMID- 16950847
TI  - Heterologously expressed GLT-1 associates in approximately 200-nm protein-lipid
      islands.
AB  - The glutamate transporter GLT-1 from Rattus norvegicus was expressed at high
      level in baby hamster kidney (BHK-21) cells by the Semliki Forest Virus
      expression system. We examined the expressed GLT-1 in the plasma membrane and
      found that the transporter accumulates in detergent-insoluble lipid-protein
      assemblies. Freeze-fracture, immunogold labeling, and electron microscopy
      revealed that GLT-1 forms approximately 200-nm protein-rich islands in the plasma
      membrane. Cholesterol depletion in living cells resulted in a dispersion of the
      GLT-1 islands, indicating that they are the result of lipid-protein rather than
      protein-protein interactions. Disruption of GLT-1 islands and dispersion of GLT-1
      goes along with a reduction of the glutamate transport activity. Our direct
      visualization of lipid-protein islands in the plasma membrane of tissue culture
      cells suggests that the reported clustering of glutamate transporters and their
      cholesterol-dependent transport activity in cells is likewise connected to their
      association with cholesterol-rich microdomains in the plasma membrane.

PMID- 16950848
TI  - Influence of lipid chemistry on membrane fluidity: tail and headgroup
      interactions.
AB  - Membrane fluidity plays an important role in cell function and may, in many
      instances, be adjusted to facilitate specific cellular processes. To understand
      better the effect that lipid chemistry has on membrane fluidity the inclusion of
      three different lipids into egg phosphatidylcholine (eggPC) bilayers has been
      examined; the three lipids are egg phosphatidylethanolamine ((eggPE) made by
      transphosphatidylation of eggPC in the presence of ethanolamine), lyso
      phosphatidylcholine (LPC), and lyso-phosphatidylethanolamine (LPE). The fluidity
      of the membranes was determined using fluorescence recovery after photobleaching
      and the intermolecular interactions were examined using attenuated total
      reflection Fourier transform infrared spectroscopy. It was observed that both
      headgroup and tail chemistry can significantly modulate lipid diffusion.
      Specifically, the inclusion of LPC and eggPE significantly altered the lipid
      diffusion, increased and decreased, respectively, whereas the inclusion of LPE
      had an intermediate effect, a slight decrease in diffusion. Strong evidence for
      the formation of hydrogen-bonds between the phosphate group and the amine group
      in eggPE and LPE was observed with infrared spectroscopy. The biological
      implications of these results are discussed.

PMID- 16950849
TI  - Neutron diffraction studies of fluid bilayers with transmembrane proteins:
      structural consequences of the achondroplasia mutation.
AB  - Achondroplasia, the most common form of human dwarfism, is due to a G380R
      mutation in the transmembrane domain of fibroblast growth factor receptor 3
      (FGFR3) in >97% of the studied cases. While the molecular mechanism of pathology
      induction is under debate, the structural consequences of the mutation have not
      been studied. Here we use neutron diffraction to determine the disposition of
      FGFR3 transmembrane domain in fluid lipid bilayers, and investigate whether the
      G380R mutation affects the topology of the protein in the bilayer. Our results
      demonstrate that, in a model system, the G380R mutation induces a shift in the
      segment that is embedded in the membrane. The center of the hydrocarbon core
      embedded segment in the mutant is close to the midpoint between R380 and R397,
      supporting previous measurements of arginine insertion energetics into the
      endoplasmic reticulum. The presented results further our knowledge about basic
      amino-acid insertion into bilayers, and may lead to new insights into the
      mechanism of pathogenesis in achondroplasia.

PMID- 16950850
TI  - The role of F-actin and myosin in epithelial cell rheology.
AB  - Although actin and myosin are important contributors to cell-force generation,
      shape change, and motility, their contributions to cell stiffness and frequency
      dependent rheology have not been conclusively determined. We apply several
      pharmacological interventions to cultured epithelial cells to elucidate the roles
      of actin and myosin in the mechanical response of cells and intracellular
      fluctuations. A suite of different methods is used to separately examine the
      mechanics of the deep cell interior and cortex, in response to depletion of
      intracellular ATP, depolymerization of F-actin, and inhibition of myosin II.
      Comparison of these results shows that F-actin plays a significant role in the
      mechanics of the cortical region of epithelial cells, but its disruption has no
      discernable effect on the rheology of the deeper interior. Moreover, we find that
      myosins do not contribute significantly to the rheology or ATP-dependent, non
      Brownian motion in the cell interior. Finally, we investigate the broad
      distribution of apparent stiffness values reported by some microrheology methods,
      which are not observed with two-point microrheology. Based on our findings and a
      simple model, we conclude that heterogeneity of the tracer-cytoskeleton contacts,
      rather than the network itself, can explain the broad distribution of apparent
      stiffnesses.

PMID- 16950851
TI  - Design of superior spider silk: from nanostructure to mechanical properties.
AB  - Spider dragline silk is of practical interest because of its excellent mechanical
      properties. However, the structure of this material is still largely unknown. In
      this article, we report what we believe is a new model of the hierarchical
      structure of silk based on scanning electron microscope and atomic force
      microscope images. This hierarchical structure includes beta-sheet, polypeptide
      chain network, and silk fibril. It turns out that an exceptionally high strength
      of the spider dragline silk can be obtained by decreasing the size of the
      crystalline nodes in the polypeptide chain network while increasing the degree of
      orientation of the crystalline nodes. Based on this understanding, how the
      reeling speed affects mechanical properties of spider dragline silk can be
      understood properly. Hopefully, the understanding obtained in this study will
      shed light on the formation of spider silk, and consequently, on the principles
      for the design of ultrastrong silk.

PMID- 16950852
TI  - The mechanical properties of E. coli type 1 pili measured by atomic force
      microscopy techniques.
AB  - The first step in the encounter between a host and a pathogen is attachment to
      the host epithelium. For uropathogenic Escherichia coli, these interactions are
      mediated by type 1 and P adhesive pili, which are long (approximately 1 microm)
      rods composed of more than 1000 protein subunits arranged in a helical structure.
      Here we used single-molecule atomic force microscopy to study the mechanical
      properties of type 1 pili. We found that type 1 pili readily extend under an
      applied force and that this extensibility is the result of unwinding the pilus
      rod's helical quaternary structure. The forced unraveling is also reversible,
      with helical rewinding taking place under considerable forces (approximately 60
      pN). These data are similar to those obtained on P pili using optical tweezers,
      indicating that these are conserved properties of uropathogenic E. coli pili. We
      also show that our data can readily be reproduced using Monte Carlo simulation
      techniques based on a two-state kinetic model. This model provides a simple way
      to extrapolate the mechanical behavior of pili under a wide range of forces. We
      propose that type 1 pilus unraveling is an essential mechanism for absorbing
      physiological shear forces encountered during urinary tract infections and
      probably essential for adhesion and colonization of the bladder epithelium.

PMID- 16950853
TI  - X-ray diffraction studies of the thick filament in permeabilized myocardium from
      rabbit.
AB  - Low angle x-ray diffraction patterns from relaxed permeabilized rabbit cardiac
      trabeculae and psoas muscle fibers were compared. Temperature was varied from 25
      degrees C to 5 degrees C at 200 mM and 50 mM ionic strengths (mu), respectively.
      Effects of temperature and mu on the intensities of the myosin layer lines (MLL),
      the equatorial intensity ratio I(1,1)/I(1,0), and the spacing of the filament
      lattice are similar in both muscles. At 25 degrees C, particularly at mu = 50 mM,
      the x-ray patterns exhibited up to six orders of MLL and sharp meridional
      reflections, signifying that myosin heads (cross-bridges) are distributed in a
      well-ordered helical array. Decreasing temperature reduced MLL intensities but
      increased I(1,1)/I(1,0). Decreases in the MLL intensities indicate increasing
      disorder in the distribution of cross-bridges on the thick filaments surface. In
      the skeletal muscle, order/disorder is directly correlated with the hydrolysis
      equilibrium of ATP by myosin, [M.ADP.P(i)]/[M.ATP]. Similar effects of
      temperature on MLL and similar biochemical ATP hydrolysis pathway found in both
      types of muscles suggest that the order/disorder states of cardiac cross-bridges
      may well be correlated with the same biochemical and structural states. This
      implies that in relaxed cardiac muscle under physiological conditions, the
      unattached cross-bridges are largely in the M.ADP.P(i) state and with the
      lowering of the temperature, the equilibrium is increasingly in favor of [M.ATP]
      and [A.M.ATP]. There appear to be some differences in the diffraction patterns
      from the two muscles, however. Mainly, in the cardiac muscle, the MLL are weaker,
      the I(1,1)/I(1,0) ratio tends to be higher, and the lattice spacing D(10),
      larger. These differences are consistent with the idea that under a wide range of
      conditions, a greater fraction of cross-bridges is weakly bound to actin in the
      myocardium.

PMID- 16950854
TI  - Hormesis outperforms threshold model in National Cancer Institute antitumor drug
      screening database.
AB  - Which dose-response model best explains low-dose responses is a critical issue in
      toxicology, pharmacology, and risk assessment. The present paper utilized the
      U.S. National Cancer Institute yeast screening database that contains 56,914 dose
      response studies representing the replicated effects of 2189 chemically diverse
      possible antitumor drugs on cell proliferation in 13 different yeast strains.
      Multiple evaluation methods indicated that the observed data are inconsistent
      with the threshold model while supporting the hormetic model. Hormetic response
      patterns were observed approximately four times more often than would be expected
      by chance alone. The data call for the rejection of the threshold model for low
      dose prediction, and they support the hormetic model as the default model for
      scientific interpretation of low-dose toxicological responses.

PMID- 16950855
TI  - Anti-pneumococcal antibody titre measurement: what useful information does it
      yield?
AB  - Measuring and interpretation of the immune response to pneumococcal
      polysaccharides is a complex field, owing to the diversity of the pneumococcal
      polysaccharide capsular types, different vaccine formulations including both
      polysaccharide and conjugate vaccines, diverse pneumococcal serological assays,
      lack of immunogenicity data for the conjugate in a number of at-risk groups and
      complex vaccine schedules. Even the reasons for performing pneumococcal serology
      can be complex, as assays may be performed for one of two reasons: either to
      assess an individual's immune status to the pneumococcus or to discriminate
      between normal and abnormal humoral immunity. This review details a history of
      the pneumococcal serological assays and provides some insight into when serology
      can prove useful, including vaccination data for certain at-risk groups.

PMID- 16950856
TI  - Cell cycle phase distribution analysis in chronic lymphocytic leukaemia: a
      significant number of cells reside in early G1-phase.
AB  - BACKGROUND AND AIMS: Chronic lymphocytic leukaemia (CLL) is a frequent non
      Hodgkin lymphoma characterised by a heterogeneous clinical course. Assessment of
      cell cycle phase kinetics might be important for prediction of clinical behaviour
      and prognosis. METHODS: Distribution of neoplastic cells in CLL within the cell
      cycle was evaluated by determining the labelling indices (LI, i.e. percentage of
      positive cells) of markers specific for late G1-phase (cyclin E), S-phase (cyclin
      A), and G2/M-phase (cyclin B1), and Mcm2, a novel marker of proliferative
      potential, in a large cohort of patients (n = 79) using tissue microarray (TMA)
      technology. Utilising a combination of these markers, an algorithm was developed-
      subtracting the combined LIs of cyclin E, cyclin A and cyclin B1 from the LI of
      Mcm2--to determine the percentage of tumour cells residing in early G1-phase,
      which is probably a critical state for the malignant potential of CLL. RESULTS:
      27.11% of cells had acquired proliferative potential as indicated by expression
      of Mcm2. Only a small number of cells were found to be in late G1-phase (7.16%),
      S-phase (3.31%) or G2/M-phase (0.98%), while 15.66% of cells were considered to
      be in early G1-phase. CONCLUSION: Cell cycle phase distribution can easily be
      assessed by immunohistochemistry in routinely processed paraffin-embedded
      specimens. A large number of neoplastic cells in CLL have proliferative
      potential, with a significant sub-population residing in early G1-phase.
      Estimates of these cells may identify cases likely to exhibit a more aggressive
      biological behaviour and adverse clinical course.

PMID- 16950857
TI  - Experiences from the front-line routine consenting of surplus surgically removed
      tissue: without investment by the National Health Service fully informed consent
      for all is not available.
AB  - The study investigated the routine introduction of a new surgical consent form
      containing a tissue consent section to investigate patient attitudes to the use
      of surplus tissue for research (after the Alder Hey inquiry) and also the
      differing approaches by consent takers. All surgical consent forms received in
      histopathology for the same 2-month period in 2 consecutive years were analysed,
      recording available information about the specimen, the tissue consent section
      and, for the second year, the consent taker. The findings showed that <5% of
      patients whose views were recorded disagreed with the use of their tissue for
      research. They also showed that the number of completed forms sent to
      histopathology had increased but the pattern of completion had changed very
      little. A wide variation between departments and also between clinicians was
      apparent in the levels of completion of the tissue consent section, suggesting
      wide variability in the quality of the consenting process. When asked, patients
      rarely object (<5%) but if the highest standards of consent for surgical tissue
      are to be achieved and the wishes of patients to donate tissue are to be
      effectively recorded then new resources or approaches will be needed for this
      process.

PMID- 16950859
TI  - Diacidic motif is required for efficient transport of the K+ channel KAT1 to the
      plasma membrane.
AB  - For a number of mammalian ion channels, trafficking to the plasma membrane was
      found to be controlled by intrinsic sequence motifs. Among these sequences are
      diacidic motifs that function as endoplasmic reticulum (ER) export signals. So
      far it is unclear if similar motifs also exist in plant ion channels. In this
      study we analyzed the function of four diacidic DXE/DXD motifs of the plant K(+)
      channel KAT1. Mutation of the first diacidic DXE motif resulted in a strong
      reduction of the KAT1 conductance in both guard cell protoplasts and HEK293 cells
      (human embryonic kidney cells). Confocal fluorescence microscopy of guard cells
      expressing the mutated KAT1 fused to green fluorescent protein revealed
      localization of the mutated channel only in intracellular structures around the
      nucleus. These structures could be identified as part of the ER via coexpression
      of KAT1 fused to yellow fluorescent protein with an ER-retained protein (HDEL)
      fused to cyan fluorescent protein. Block of vesicle formation from the ER by
      overexpression of the small GTP-binding protein Sar1 fixed in its GDP-bound form
      led to retention of wild-type KAT1 in similar parts of the ER. Mutation of the
      three other diacidic motifs had no effect. Together, the results demonstrate that
      one diacidic motif of KAT1 is essential for ER export of the functional channel
      in both guard cell protoplasts and HEK293 cells. This suggests that trafficking
      of plant plasma membrane ion channels is controlled via a conserved mechanism.

PMID- 16950858
TI  - Mucosa-associated lymphoid tissue (MALT) lymphoma: a practical guide for
      pathologists.
AB  - Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT
      lymphoma) is the third most common non-Hodgkin lymphoma subtype, accounting for
      around 6-8% of all non-Hodgkin lymphomas in the Western hemisphere. Although MALT
      lymphomas are clinically indolent, the disease is typically chronic, requiring
      long-term clinical surveillance and, often, repeated biopsies. Pathologists thus
      play a central role in the diagnosis and management of these patients. The
      optimal diagnosis and management of a MALT lymphoma requires careful integration
      of morphological, immunohistochemical and molecular information, together with
      close cooperation with the clinician treating the patient. This review discusses
      recent developments in the molecular pathogenesis of MALT lymphoma and provides
      strategies for integrating this information into daily pathological practice.

PMID- 16950860
TI  - Molecular identification of an Arabidopsis S-adenosylmethionine transporter.
      Analysis of organ distribution, bacterial expression, reconstitution into
      liposomes, and functional characterization.
AB  - Despite much study of the role of S-adenosylmethionine (SAM) in the methylation
      of DNA, RNA, and proteins, and as a cofactor for a wide range of biosynthetic
      processes, little is known concerning the intracellular transport of this
      essential metabolite. Screening of the Arabidopsis (Arabidopsis thaliana) genome
      yielded two potential homologs of yeast (Saccharomyces cerevisiae) and human SAM
      transporters, designated as SAMC1 and SAMC2, both of which belong to the
      mitochondrial carrier protein family. The SAMC1 gene is broadly expressed at the
      organ level, although only in specialized tissues of roots with high rates of
      cell division, and appears to be up-regulated in response to wounding stress,
      whereas the SAMC2 gene is very poorly expressed in all organs/tissues analyzed.
      Direct transport assays with the recombinant and reconstituted SAMC1 were
      utilized to demonstrate that this protein displays a very narrow substrate
      specificity confined to SAM and its closest analogs. Further experiments revealed
      that SAMC1 was able to function in uniport and exchange reactions and
      characterized the transporter as highly active, but sensitive to physiologically
      relevant concentrations of S-adenosylhomocysteine, S-adenosylcysteine, and
      adenosylornithine. Green fluorescent protein-based cell biological analysis
      demonstrated targeting of SAMC1 to mitochondria. Previous proteomic analyses
      identified this protein also in the chloroplast inner envelope. In keeping with
      these results, bioinformatics predicted dual localization for SAMC1. These
      findings suggest that the provision of cytosolically synthesized SAM to
      mitochondria and possibly also to plastids is mediated by SAMC1 according to the
      relative demands for this metabolite in the organelles.

PMID- 16950861
TI  - The cellulose synthase gene superfamily and biochemical functions of xylem
      specific cellulose synthase-like genes in Populus trichocarpa.
AB  - Wood from forest trees modified for more cellulose or hemicelluloses could be a
      major feedstock for fuel ethanol. Xylan and glucomannan are the two major
      hemicelluloses in wood of angiosperms. However, little is known about the genes
      and gene products involved in the synthesis of these wood polysaccharides. Using
      Populus trichocarpa as a model angiosperm tree, we report here a systematic
      analysis in various tissues of the absolute transcript copy numbers of cellulose
      synthase superfamily genes, the cellulose synthase (CesA) and the hemicellulose
      related cellulose synthase-like (Csl) genes. Candidate Csl genes were
      characterized for biochemical functions in Drosophila Schneider 2 (S2) cells. Of
      the 48 identified members, 37 were found expressed in various tissues. Seven CesA
      genes are xylem specific, suggesting gene networks for the synthesis of wood
      cellulose. Four Csl genes are xylem specific, three of which belong to the CslA
      subfamily. The more xylem-specific CslA subfamily is represented by three types
      of members: PtCslA1, PtCslA3, and PtCslA5. They share high sequence homology, but
      their recombinant proteins produced by the S2 cells exhibited distinct substrate
      specificity. PtCslA5 had no catalytic activity with the substrates for xylan or
      glucomannan. PtCslA1 and PtCslA3 encoded mannan synthases, but PtCslA1 further
      encoded a glucomannan synthase for the synthesis of (1-->4)-beta-D-glucomannan.
      The expression of PtCslA1 is most highly xylem specific, suggesting a key role
      for it in the synthesis of wood glucomannan. The results may help guide further
      studies to learn about the regulation of cellulose and hemicellulose synthesis in
      wood.

PMID- 16950862
TI  - Glutamate:glyoxylate aminotransferase modulates amino acid content during
      photorespiration.
AB  - In photorespiration, peroxisomal glutamate:glyoxylate aminotransferase (GGAT)
      catalyzes the reaction of glutamate and glyoxylate to produce 2-oxoglutarate and
      glycine. Previous studies demonstrated that alanine aminotransferase-like protein
      functions as a photorespiratory GGAT. Photorespiratory transamination to
      glyoxylate, which is mediated by GGAT and serine glyoxylate aminotransferase
      (SGAT), is believed to play an important role in the biosynthesis and metabolism
      of major amino acids. To better understand its role in the regulation of amino
      acid levels, we produced 42 GGAT1 overexpression lines that express different
      levels of GGAT1 mRNA. The levels of free serine, glycine, and citrulline
      increased markedly in GGAT1 overexpression lines compared with levels in the wild
      type, and levels of these amino acids were strongly correlated with levels of
      GGAT1 mRNA and GGAT activity in the leaves. This accumulation began soon after
      exposure to light and was repressed under high levels of CO(2). Light and
      nutrient conditions both affected the amino acid profiles; supplementation with
      NH(4)NO(3) increased the levels of some amino acids compared with the controls.
      The results suggest that the photorespiratory aminotransferase reactions
      catalyzed by GGAT and SGAT are both important regulators of amino acid content.

PMID- 16950863
TI  - Characterization of a mitogen-activated protein kinase gene from cucumber
      required for trichoderma-conferred plant resistance.
AB  - The fungal biocontrol agent Trichoderma asperellum has been recently shown to
      induce systemic resistance in plants through a mechanism that employs jasmonic
      acid and ethylene signal transduction pathways. Mitogen-activated protein kinase
      (MAPK) proteins have been implicated in the signal transduction of a wide variety
      of plant stress responses. Here we report the identification and characterization
      of a Trichoderma-induced MAPK (TIPK) gene function in cucumber (Cucumis sativus).
      Similar to its homologs, wound-induced protein kinase, MPK3, and MPK3a, TIPK is
      also induced by wounding. Normally, preinoculation of roots with Trichoderma
      activates plant defense mechanisms, which result in resistance to the leaf
      pathogen Pseudomonas syringae pv lachrymans. We used a unique attenuated virus
      vector, Zucchini yellow mosaic virus (ZYMV-AGII), to overexpress TIPK protein and
      antisense (AS) RNA. Plants overexpressing TIPK were more resistant to pathogenic
      bacterial attack than control plants, even in the absence of Trichoderma
      preinoculation. On the other hand, plants expressing TIPK-AS revealed increased
      sensitivity to pathogen attack. Moreover, Trichoderma preinoculation could not
      protect these AS plants against subsequent pathogen attack. We therefore
      demonstrate that Trichoderma exerts its protective effect on plants through
      activation of the TIPK gene, a MAPK that is involved in signal transduction
      pathways of defense responses.

PMID- 16950864
TI  - Deaf people communicating via SMS, TTY, relay service, fax, and computers in
      Australia.
AB  - Despite the expansion of Deaf people's use of communication technology little is
      published about how they use electronic communication in their social and working
      lives and the implications for their concepts of identity and community.
      Australia is an ideal research base because the use of a range of technologies is
      widespread there. To gain access to a wide age range of people who identify as
      Deaf, members of the national organization, the Australian Association of the
      Deaf, were surveyed by mail. Results showed that Short Message Service (SMS),
      telephone typewriters (TTY), voice/TTY relay services, fax, and e-mail were used
      regularly. Deaf users are discerning of the purposes for which they use each
      method: SMS for social and personal interactions, TTY for longer communications
      and (via the relay service) with people and services without TTYs, fax for
      business and social contact, and computers for personal and business e-mails as
      well as Web browsing, accessing chat rooms, word processing, games, and study.

PMID- 16950865
TI  - Mental health in deaf adults: symptoms of anxiety and depression among hearing
      and deaf individuals.
AB  - Individuals with disabilities encounter practical and social problems beyond
      those experienced by nondisabled individuals. This extra burden may in turn
      increase the risk of developing mental health problems. The objective of this
      article is to disclose the mental health situation among deaf individuals
      compared to a control sample of hearing individuals. The analyses are based on
      two separate Norwegian postal surveys, one among the general population (1995
      1997) and one among the deaf population (2001). A shortened version of the
      Hopkins Symptom Checklist was used to disclose the degree of mental distress
      among the respondents. Three questions common to the studies were analyzed to
      determine differences between the two groups. Analyses revealed that the deaf
      respondents showed significantly more symptoms of mental health problems than the
      hearing respondents. The results point to the need for focussing more attention
      on the mental health of deaf children and adults. Society must be made aware of
      the special risks that deaf children and adults encounter with respect to mental
      health.

PMID- 16950866
TI  - Functional anatomy and interaction of fast and slow visual pathways in macaque
      monkeys.
AB  - We measured the timing, areal distribution, and laminar profile of fast,
      wavelength-insensitive and slower, wavelength-sensitive responses in V1 and
      extrastriate areas, using laminar current-source density analysis in awake
      macaque monkeys. There were 3 main findings. 1) We confirmed previously reported
      significant ventral-dorsal stream latency lags at the level of V4 (V4 mean = 38.7
      ms vs. middle temporal mean = 26.9 ms) and inferotemporal cortex (IT mean = 43.4
      ms vs. dorsal bank of the superior temporal sulcus mean = 33.9 ms). 2) We found
      that wavelength-sensitive inputs in areas V1, V4, and IT lagged the wavelength
      insensitive responses by significant margins; this lag increased over successive
      levels of the system. 3) We found that laminar activation profiles in V4 and IT
      were inconsistent with "feedforward" input through the ascending ventral cortical
      pathway; the likely alternative input routes include both lateral inputs from the
      dorsal stream and direct inputs from nonspecific thalamic neurons. These findings
      support a "Framing" Model of ventral stream visual processing in which rapidly
      conducted inputs, mediated by one or more accessory pathways, modulate the
      processing of more slowly conducted feedforward inputs.

PMID- 16950867
TI  - Rapid cortical oscillations and early motor activity in premature human neonate.
AB  - Delta-brush is the dominant pattern of rapid oscillatory activity (8-25 Hz) in
      the human cortex during the third trimester of gestation. Here, we studied the
      relationship between delta-brushes in the somatosensory cortex and spontaneous
      movements of premature human neonates of 29-31 weeks postconceptional age using a
      combination of scalp electroencephalography and monitoring of motor activity. We
      found that sporadic hand and foot movements heralded the appearance of delta
      brushes in the corresponding areas of the cortex (lateral and medial regions of
      the contralateral central cortex, respectively). Direct hand and foot stimulation
      also reliably evoked delta-brushes in the same areas. These results suggest that
      sensory feedback from spontaneous fetal movements triggers delta-brush
      oscillations in the central cortex in a somatotopic manner. We propose that in
      the human fetus in utero, before the brain starts to receive elaborated sensory
      input from the external world, spontaneous fetal movements provide sensory
      stimulation and drive delta-brush oscillations in the developing somatosensory
      cortex contributing to the formation of cortical body maps.

PMID- 16950869
TI  - Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells.
AB  - Zip14 is a member of the SLC39A zinc transporter family, which is involved in
      zinc uptake by cells. Up-regulation of Zip14 by IL-6 appears to contribute to the
      hepatic zinc accumulation and hypozincemia of inflammation. At least three
      members of the SLC39A family transport other trace elements, such as iron and
      manganese, in addition to zinc. We analyzed the capability of Zip14 to mediate
      non-transferrin-bound iron (NTBI) uptake by overexpressing mouse Zip14 in HEK
      293H cells and Sf9 insect cells. Zip14 was found to localize to the plasma
      membrane, and its overexpression increased the uptake of both (65)Zn and (59)Fe.
      Addition of bathophenanthroline sulfonate, a cell-impermeant ferrous iron
      chelator, inhibited Zip14-mediated iron uptake from ferric citrate, suggesting
      that iron is taken up by HEK cells as Fe(2+). Iron uptake by HEK and Sf9 cells
      expressing Zip14 was inhibited by zinc. Suppression of endogenous Zip14
      expression by using Zip14 siRNA reduced the uptake of both iron and zinc by AML12
      mouse hepatocytes. Zip14 siRNA treatment also decreased metallothionein mRNA
      levels, suggesting that compensatory mechanisms were not sufficient to restore
      intracellular zinc. Collectively, these results indicate that Zip14 can mediate
      the uptake of zinc and NTBI into cells and that it may play a role in zinc and
      iron metabolism in hepatocytes, where this transporter is abundantly expressed.
      Because NTBI is commonly found in plasma of patients with hemochromatosis and
      transfusional iron overload, Zip14-mediated NTBI uptake may contribute to the
      hepatic iron loading that characterizes these diseases.

PMID- 16950870
TI  - Lysosomal storage disease upon disruption of the neuronal chloride transport
      protein ClC-6.
AB  - Mammalian CLC proteins function as Cl(-) channels or as electrogenic Cl(-)/H(+)
      exchangers and are present in the plasma membrane and intracellular vesicles. We
      now show that the ClC-6 protein is almost exclusively expressed in neurons of the
      central and peripheral nervous systems, with a particularly high expression in
      dorsal root ganglia. ClC-6 colocalized with markers for late endosomes in
      neuronal cell bodies. The disruption of ClC-6 in mice reduced their pain
      sensitivity and caused moderate behavioral abnormalities. Neuronal tissues showed
      autofluorescence at initial axon segments. At these sites, electron microscopy
      revealed electron-dense storage material that caused a pathological enlargement
      of proximal axons. These deposits were positive for several lysosomal proteins
      and other marker proteins typical for neuronal ceroid lipofuscinosis (NCL), a
      lysosomal storage disease. However, the lysosomal pH of Clcn6(-/-) neurons
      appeared normal. CLCN6 is a candidate gene for mild forms of human NCL. Analysis
      of 75 NCL patients identified ClC-6 amino acid exchanges in two patients but
      failed to prove a causative role of CLCN6 in that disease.

PMID- 16950871
TI  - Control of growth and positional information by the graded vestigial expression
      pattern in the wing of Drosophila melanogaster.
AB  - The size and shape of organs depend on cellular processes such as cell
      proliferation, cell survival, and spatial arrangement of cells. In turn, all of
      these processes are a consequence of positional identity of individual cells in
      whole organs. Links of positional information with organ growth and pattern
      expression of genes is a little-addressed question. We show that differences in
      vestigial expression between neighboring cells of the wing blade autonomously and
      nonautonomously affect cell proliferation along the proximo-distal axis. On the
      other hand, uniform expression of vestigial inhibits cell proliferation and also
      perturbs the shape of wing blade altering the preferential orientation of cell
      divisions. Our observations provide evidence that local cell interactions,
      triggered by differences in vestigial expression between neighboring cells,
      confer positional values operating in the control of growth and shape of the
      wing.

PMID- 16950872
TI  - Chiral-selective aminoacylation of an RNA minihelix: Mechanistic features and
      chiral suppression.
AB  - Aminoacylation of RNA minihelices is speculated to be a key step in the
      transition from the putative RNA world to the theater of proteins. This reaction
      affords the opportunity to make chiral selection of an l- or d-amino acid and
      thus determine the ultimate chirality that is incorporated into proteins.
      Previous work showed chiral preference of aminoacylation with a nonprotein,
      nonribozyme, RNA-directed aminoacylation system. This preference was, in turn,
      determined by the preexisting chirality of the RNA. The alpha-amino group
      attached to the asymmetric alpha-carbon of the amino acid was an obvious
      candidate to play a role in chiral selectivity through interactions with the RNA.
      Also not clear was whether a simple manipulation could change the chiral
      selectivity, thereby giving insight into the basis of chiral selection in the
      first place. Here we show, surprisingly, no role for the free alpha-amino group
      in chiral selection. However, by a sequence manipulation, chiral preference was
      suppressed and partly reversed. This result and those with further RNA constructs
      support the idea that the chiral preference for an l-amino acid in these
      constructs depends on avoiding a sugar-pucker-sensitive steric clash between a
      pendant group of a base with the amino acid side chain.

PMID- 16950873
TI  - New building blocks in the 2/1 crystalline approximant of a Bergman-type
      icosahedral quasicrystal.
AB  - The refined x-ray crystal structure of the phase Mg(27)Al(10.7(2))Zn(47.3(2))
      (Pa3) establishes it as the new 2/1 Bergman-type approximant of the icosahedral
      quasicrystal. The primitive cubic lattice consists of condensed triacontahedral
      and novel prolate rhombohedral (PR) clusters. Each triacontahedron encapsulates
      the traditional, multiply endohedral Bergman-type clusters, and each PR
      encapsulates an Al(2) dimer. This phase exhibits the same long-range order as
      recently established for the Tsai-type Sc-Mg-Zn 2/1 approximant crystal, with
      substantial geometric and atomic distribution differences between the two only in
      the short range orders. This common feature suggests that Bergman- and Tsai-type
      quasicrystals may be more similar than earlier conceived. Factors germane to the
      formation of, and the differences between, Bergman- vs. Tsai-type 1/1 and 2/1
      approximate structures are considered, including notably different distributions
      of the more electropositive elements.

PMID- 16950874
TI  - Enhancement of antinociception by coadministration of nonsteroidal anti
      inflammatory drugs and soluble epoxide hydrolase inhibitors.
AB  - Combination therapies have long been used to treat inflammation while reducing
      side effects. The present study was designed to evaluate the therapeutic
      potential of combination treatment with nonsteroidal anti-inflammatory drugs
      (NSAIDs) and previously undescribed soluble epoxide hydrolase inhibitors (sEHIs)
      in lipopolysaccharide (LPS)-challenged mice. NSAIDs inhibit cyclooxygenase (COX)
      enzymes and thereby decrease production of metabolites that lead to pain and
      inflammation. The sEHIs, such as 12-(3-adamantan-1-yl-ureido)-dodecanoic acid
      butyl ester (AUDA-BE), stabilize anti-inflammatory epoxy-eicosatrienoic acids,
      which indirectly reduce the expression of COX-2 protein. Here we demonstrate that
      the combination therapy of NSAIDs and sEHIs produces significantly beneficial
      effects that are additive for alleviating pain and enhanced effects in reducing
      COX-2 protein expression and shifting oxylipin metabolomic profiles. When
      administered alone, AUDA-BE decreased protein expression of COX-2 to 73 +/- 6% of
      control mice treated with LPS only without altering COX-1 expression and
      decreased PGE(2) levels to 52 +/- 8% compared with LPS-treated mice not receiving
      any therapeutic intervention. When AUDA-BE was used in combination with low doses
      of indomethacin, celecoxib, or rofecoxib, PGE(2) concentrations dropped to 51 +/-
      7, 84 +/- 9, and 91 +/- 8%, respectively, versus LPS control, without disrupting
      prostacyclin and thromboxane levels. These data suggest that these drug
      combinations (NSAIDs and sEHIs) produce a valuable beneficial analgesic and anti
      inflammatory effect while prospectively decreasing side effects such as
      cardiovascular toxicity.

PMID- 16950875
TI  - Amber from western Amazonia reveals Neotropical diversity during the middle
      Miocene.
AB  - Tertiary insects and arachnids have been virtually unknown from the vast western
      Amazonian basin. We report here the discovery of amber from this region
      containing a diverse fossil arthropod fauna (13 hexapod families and 3 arachnid
      species) and abundant microfossil inclusions (pollen, spores, algae, and
      cyanophyceae). This unique fossil assemblage, recovered from middle Miocene
      deposits of northeastern Peru, greatly increases the known diversity of Cenozoic
      tropical-equatorial arthropods and microorganisms and provides insights into the
      biogeography and evolutionary history of modern Neotropical biota. It also
      strengthens evidence for the presence of more modern, high-diversity tropical
      rainforest ecosystems during the middle Miocene in western Amazonia.

PMID- 16950877
TI  - Stable four-pi-electron, four-membered heterocyclic cations and carbenes.
AB  - Replacement of halide from N-(haloboryl)formamidines for the weakly coordinating
      anion [B(C(6)F(5))(4)](-), using [Et(3)Si(toluene)](+)[B(C(6)F(5))(4)](-),
      induces a ring closure leading to the cationic four-pi-electron four-membered
      heterocycles [HC(N-2,6-diisopropylphenyl)(2)BR](+) [R = N(i-Pr)(2), Ph].
      Subsequent deprotonation of the B-amino derivative affords the corresponding N
      heterocyclic carbene, which has been isolated as yellow crystals. According to
      single-crystal x-ray diffraction studies, both the carbene and its conjugate acid
      precursor have a planar structure, with no pyramidalization of the ring atoms.
      The structural parameters indicate that the four pi electrons are mostly
      distributed over the N-C-N fragment with little involvement of the boron center,
      and therefore both types of heterocycles escape from antiaromaticity. However,
      considering the ring strain and the presence of the Lewis acid center, the
      thermal stability of the carbene (mp 98 degrees C without decomposition) is
      rather surprising. These results clearly suggest that the backbone of N
      heterocyclic carbenes can be modified at will, without preventing their
      isolation.

PMID- 16950876
TI  - An aged host promotes the evolution of avirulent coxsackievirus into a virulent
      strain.
AB  - The emergence of new, more pathogenic viruses necessitates elucidation of factors
      that promote viral evolution. Aging, a potential factor, is associated with
      increased susceptibility to viral infections. We used the enterovirus
      coxsackievirus B3 (CVB3) to investigate the effects of host age on pathogenicity
      and viral gene sequence. Old mice infected with a normally amyocarditic strain of
      CVB3, CVB3/0, had significantly higher mean heart viral titers compared with
      CVB3/0-infected adult mice. To determine whether a change in the CVB3/0 viral
      population could contribute to the higher titers observed in the old infected
      mice, CVB3/0 was passed once through an old or adult host and the changes in
      pathogenicity and viral genome were examined after subsequent infection of old or
      adult mice. Adult mice infected with CVB3/0 that was passed through an old host
      (CVB3/0(Old)) exhibited significantly higher heart viral titers, pathology, and
      weight loss than adult mice infected with either stock CVB3/0 or CVB3/0 passed
      through an adult host (CVB3/0(Adult)). Sequence analysis of virus isolated from
      CVB3/0(Old)-infected mice revealed 13 specific and reproducible nucleotide
      changes. These changes result in a sequence that matches the virulent CVB3/20
      strain and are associated with promoting cardiovirulence. In contrast, we
      observed only one nucleotide change, low heart viral titers, and no heart and
      liver pathology in adult mice infected with CVB3/0(Adult). These results
      demonstrate that the aged host promotes rapid selection of a pathogenic variant
      of CVB3 from an avirulent strain and introduces a host-virus paradigm for studies
      of viral infection in the aged.

PMID- 16950878
TI  - A microrotary motor powered by bacteria.
AB  - Biological molecular motors have a number of unique advantages over artificial
      motors, including efficient conversion of chemical energy into mechanical work
      and the potential for self-assembly into larger structures, as is seen in muscle
      sarcomeres and bacterial and eukaryotic flagella. The development of an
      appropriate interface between such biological materials and synthetic devices
      should enable us to realize useful hybrid micromachines. Here we describe a
      microrotary motor composed of a 20-mum-diameter silicon dioxide rotor driven on a
      silicon track by the gliding bacterium Mycoplasma mobile. This motor is fueled by
      glucose and inherits some of the properties normally attributed to living
      systems.

PMID- 16950880
TI  - Accurately quantifying low-abundant targets amid similar sequences by revealing
      hidden correlations in oligonucleotide microarray data.
AB  - Microarrays have enabled the determination of how thousands of genes are
      expressed to coordinate function within single organisms. Yet applications to
      natural or engineered communities where different organisms interact to produce
      complex properties are hampered by theoretical and technological limitations.
      Here we describe a general method to accurately identify low-abundant targets in
      systems containing complex mixtures of homologous targets. We combined an
      analytical predictor of nonspecific probe-target interactions (cross
      hybridization) with an optimization algorithm that iteratively deconvolutes true
      probe-target signal from raw signal affected by spurious contributions (cross
      hybridization, noise, background, and unequal specific hybridization response).
      The method was capable of quantifying, with unprecedented specificity and
      accuracy, ribosomal RNA (rRNA) sequences in artificial and natural communities.
      Controlled experiments with spiked rRNA into artificial and natural communities
      demonstrated the accuracy of identification and quantitative behavior over
      different concentration ranges. Finally, we illustrated the power of this
      methodology for accurate detection of low-abundant targets in natural
      communities. We accurately identified Vibrio taxa in coastal marine samples at
      their natural concentrations (<0.05% of total bacteria), despite the high
      potential for cross-hybridization by hundreds of different coexisting rRNAs,
      suggesting this methodology should be expandable to any microarray platform and
      system requiring accurate identification of low-abundant targets amid pools of
      similar sequences.

PMID- 16950881
TI  - Evaluation of disulfide reduction during receptor-mediated endocytosis by using
      FRET imaging.
AB  - Despite functional evidence for disulfide bond-reducing activity in endosomal
      compartments, the mechanistic details pertaining to such process (e.g., kinetics
      and sites of disulfide reduction) remain largely controversial. To address these
      questions directly, we have synthesized a previously uncharacterized fluorescent
      folate conjugate, folate-(BODIPY FL)-SS-rhodamine (folate-FRET), that changes
      fluorescence from red to green upon disulfide bond reduction. Using this
      construct, we have observed that disulfide reduction: (i) occurs with a half-time
      of 6 h after folate-FRET endocytosis, (ii) begins in endosomes and does not
      depend significantly on redox machinery located on the cell surface or within the
      lysosome or the Golgi apparatus, (iii) occurs independently of endocytic vesicle
      trafficking along microtubules, and (iv) yields products that are subsequently
      sorted into distinct endosomes and trafficked in different directions. Finally,
      colocalization of folate and transferrin receptors suggest that conclusions
      derived from this study may apply to other endocytic pathways.

PMID- 16950882
TI  - Hyperinsulinaemia, hyperaminoacidaemia and post-exercise muscle anabolism: the
      search for the optimal recovery drink.
AB  - Dietary supplements and other ergogenic aids are popular among athletes. Recent
      studies have shown that nutritional mixtures containing protein hydrolysates,
      added leucine, and high-glycaemic carbohydrates greatly augment insulin secretion
      compared with high-glycaemic carbohydrates only. When post-exercise
      hyperinsulinaemia is supported by hyperaminoacidaemia induced by protein
      hydrolysate and leucine ingestion, net protein deposition in muscle should occur.
      Thus, consumption of post-exercise recovery drinks containing these nutrients in
      conjunction with appropriate resistance training may lead to increased skeletal
      muscle hypertrophy and strength. However, the long-term effects on body
      composition and exercise performance remain to be determined.

PMID- 16950884
TI  - COX-2 inhibitors in sports medicine: utility and controversy.

PMID- 16950883
TI  - Coronary risk in a cohort of Paralympic athletes.
AB  - OBJECTIVE: To determine the prevalence of coronary risk factors in Paralympic
      athletes and evaluate their risk of coronary events. METHOD: An observational
      prospective cross sectional study of 79 consecutive Brazilian Paralympic athletes
      (mean (SD) age 27.8 (6.7) years (median 26 years)). There were 56 men and 23
      women, 67 with physical and 12 with visual disabilities. The occurrence of
      systemic hypertension, hypercholesterolaemia, diabetes mellitus, smoking,
      familial antecedents, obesity, and hypertriglyceridaemia was investigated. The
      risk of coronary events was calculated using the American Heart Association
      Coronary risk handbook, and also the 10 year probability of a coronary event
      using the Framingham risk score. RESULTS: The prevalence of risk factors was:
      systemic hypertension, 11%; familial antecedents, 10%; smoking, 9%;
      hypertriglyceridaemia, 6%; hypercholesterolaemia, 1.3%; obesity, 4%; diabetes,
      0%. They occurred in 51% of the Paralympic athletes: one factor (41%), two
      factors (4%), and three factors (6%). The risk of coronary events was absent in
      80%, slight in 17%, and moderate in 3%. This could only be evaluated in 81% of
      the athletes, as 8% had amputations, 9% were young, and 2% had unknown familial
      antecedents. The Framingham risk score ranged from -14 to +6, predicting a 10
      year probability of a coronary event of 3.3 (3.8)%. CONCLUSION: This study shows
      a reasonably high prevalence of coronary risk factors (51%), despite a low
      probability of coronary events in Paralympic athletes. The lipid and blood
      pressure profiles were similar in ambulatory and wheelchair athletes.

PMID- 16950885
TI  - Reactivity, stability, and strength performance capacity in motor sports.
AB  - BACKGROUND: Racing drivers require multifaceted cognitive and physical abilities
      in a multitasking situation. A knowledge of their physical capacities may help to
      improve fitness and performance. OBJECTIVE: To compare reaction time, stability
      performance capacity, and strength performance capacity of elite racing drivers
      with those of age-matched, physically active controls. METHODS: Eight elite
      racing drivers and 10 physically active controls matched for age and weight were
      tested in a reaction and determination test requiring upper and lower extremity
      responses to visual and audio cues. Further tests comprised evaluation of one-leg
      postural stability on a two-dimensional moveable platform, measures of maximum
      strength performance capacity of the extensors of the leg on a leg press, and a
      test of force capacity of the arms in a sitting position at a steering wheel. An
      additional arm endurance test consisted of isometric work at the steering wheel
      at +30 degrees and -30 degrees where an eccentric threshold load of 30 N.m was
      applied. Subjects had to hold the end positions above this threshold until
      exhaustion. Univariate one way analysis of variance (alpha = 0.05) including a
      Bonferroni adjustment was used to detect group differences between the drivers
      and controls. RESULTS: The reaction time of the racing drivers was significantly
      faster than the controls (p = 0.004). The following motor reaction time and
      reaction times in the multiple determination test did not differ between the
      groups. No significant differences (p>0.05) were found for postural stability,
      leg extensor strength, or arm strength and endurance. CONCLUSIONS: Racing drivers
      have faster reaction times than age-matched physically active controls. Further
      development of motor sport-specific test protocols is suggested. According to the
      requirements of motor racing, strength and sensorimotor performance capacity can
      potentially be improved.

PMID- 16950886
TI  - Geographical and age-stratified distributions of foot-and-mouth disease virus
      seropositive and probang-positive cattle herds in the Adamawa province of
      Cameroon.
AB  - Six of the seven known serotypes of foot-and-mouth disease (FMD) virus occur in
      Africa. This paper describes the results of a population-based cross-sectional
      study of the seroprevalence of FMD and the persistence of the virus in cattle
      herds and associated sheep flocks in the Adamawa province of Cameroon. Antibody
      titres measured by the virus neutralising test indicated that serotypes O, A and
      SAT2 viruses had been circulating in the province. The estimates of apparent
      seroprevalence in cattle herds, based on five juvenile animals (eight to 24
      months old) per herd, were 74.8 per cent for serotype SAT2, 30.8 per cent for
      serotype A and 11.2 per cent for serotype O, indicating recent exposure; the
      estimates based on animals more than 24 months of age were 91.1 per cent for
      SAT2, 83.6 per cent for A and 34.2 per cent for serotype O. Epithelial and
      oropharyngeal samples were collected from cattle and small ruminants, cultured
      and typed by ELISA; serotypes A and SAT2 were isolated from both types of sample.
      The herd-level estimate of apparent prevalence of probang-positive herds was 19.5
      per cent and the animal-level estimate of apparent prevalence was 3.4 per cent.
      The geographical distribution of the seropositive herds based on juveniles
      suggested that recent SAT2 exposure was widespread and particularly high in the
      more northern and western parts of the province, whereas recent exposure to
      serotype A was patchy and more concentrated in the south and east. This
      distribution corresponded very closely with the distribution of herds from which
      virus was recovered by probang, indicating recent exposure or infection. No
      serotype O viruses were recovered from cattle, and the distribution of
      seropositive herds suggested very localised recent exposure. The apparent
      prevalence of probang-positive animals declined with the age of the animal and
      the period since the last recorded outbreak in the herd.

PMID- 16950879
TI  - Molecular characterization of embryonic gonads by gene expression profiling in
      Drosophila melanogaster.
AB  - In many animal species, germ-line progenitors associate with gonadal somatic
      cells to form the embryonic gonads (EGs) that later develop into functional organ
      producing gametes. To explore the genetic regulation of the germ-line
      development, we initiated a comprehensive identification and functional analysis
      of the genes expressed within the EGs. First, we generated a cDNA library from
      gonads purified from Drosophila embryos by FACS. Using this library, we
      catalogued the genes expressed in the gonad by EST analysis. A total of 17,218
      high-quality ESTs representing 3,051 genes were obtained, corresponding to 20% of
      the predicted genes in the genome. The EG transcriptome is unexpectedly distinct
      from that of adult gonads and includes an extremely high proportion of
      retrotransposon-derived transcripts. We verified 101 genes preferentially
      expressed in the EGs by whole-mount in situ hybridization. Within this subset, 39
      and 58 genes were expressed predominantly in germ-line and somatic cells,
      respectively, whereas four genes were expressed in the both cell lineages. The
      gonad-enriched genes encompassed a variety of predicted functions. However, genes
      implicated in SUMOylation and protein translation, including germ-line-specific
      ribosomal proteins, are preferentially expressed in the germ line, whereas the
      expression of various retrotransposons and RNAi-related genes are more prominent
      in the gonadal soma. These transcriptome data are a resource for understanding
      the mechanism of various cellular events during germ-line development.

PMID- 16950888
TI  - Detection of pigeon circovirus in cloacal swabs: implications for diagnosis,
      epidemiology and control.
AB  - Pigeon circovirus (picv) was detected in cloacal swab samples by means of a newly
      developed, sensitive pcr. An initial investigation of 17 Belgian racing pigeons
      aged up to eight months showed that rates of detection of 88 per cent and above
      were achieved using samples of cloacal swab, blood and bursa of Fabricius. The
      sampling of 15 caged pigeons six times when they were from three to 31 weeks of
      age indicated that picv infections were more readily detected in cloacal swabs
      than in blood, and that the virus could be detected in cloacal swabs for longer
      periods after infection than in blood. picv infections were detected in cloacal
      swabs from 38 of 47 young pigeons aged from two to 31 weeks, from 12 racing
      lofts, which had clinical signs including diarrhoea and weight loss,
      regurgitation and respiratory signs. Samples from birds from two infected lofts
      indicated that picv could be detected in some birds for at least 27 weeks.
      Although nine of 14 pigeons aged from 32 to 45 weeks were virus-positive, picv
      was detected in only one of 18 adult pigeons that originated from four infected
      lofts.

PMID- 16950887
TI  - Comparison of flank and midline approaches to the ovariohysterectomy of cats.
AB  - In a survey of uk veterinary practitioners, 96 per cent indicated that they
      performed ovariohysterectomy on cats via flank laparatomy rather than a midline
      coeliotomy. At a veterinary teaching hospital 32 cats were spayed by the midline
      approach and 34 by the flank approach, by undergraduate students under the
      continuous supervision of a veterinary surgeon. The duration of each part of the
      procedures was recorded and information was obtained from the students, the
      supervisors and the owners of the cats by means of questionnaires. The total
      duration of the surgery and the students' assessment of the difficulty of the
      surgery were not significantly different between the two groups. The time taken
      from the skin incision to entering the peritoneum was significantly longer with
      the flank approach, but finding the uterus took significantly longer with the
      midline approach. There was a high incidence of wound complications, in the form
      of swelling, redness or discharges, but the only statistically significant
      difference between the groups was a greater incidence of discharges in the cats
      spayed via the flank (five cases) than in the cats spayed via the midline (one
      case).

PMID- 16950889
TI  - Survey of eyeworm (Thelazia species) in wild deer in southern England.

PMID- 16950890
TI  - Horner's syndrome in an eastern screech owl (Megascops asio).

PMID- 16950891
TI  - Budd-Chiari-like syndrome caused by a congenital hiatal hernia in a shar-pei dog.

PMID- 16950892
TI  - Prion protein in kidneys of scrapie-infected sheep.

PMID- 16950893
TI  - Bluetongue in northern Europe.

PMID- 16950894
TI  - Bluetongue in northern Europe.

PMID- 16950895
TI  - Withdrawal period for Regumate Porcine.

PMID- 16950896
TI  - Engineering of primary carbohydrate metabolism for increased production of
      actinorhodin in Streptomyces coelicolor.
AB  - The objectives of the current studies were to determine the roles of key enzymes
      in central carbon metabolism in the context of increased production of
      antibiotics in Streptomyces coelicolor. Genes for glucose-6-phosphate
      dehydrogenase and phosphoglucomutase (Pgm) were deleted and those for the acetyl
      coenzyme A carboxylase (ACCase) were overexpressed. Under the conditions tested,
      glucose-6-phosphate dehydrogenase encoded by zwf2 plays a more important role
      than that encoded by zwf1 in determining the carbon flux to actinorhodin (Act),
      while the function of Pgm encoded by SCO7443 is not clearly understood. The pgm
      deleted mutant unexpectedly produced abundant glycogen but was impaired in Act
      production, the exact reverse of what had been anticipated. Overexpression of the
      ACCase resulted in more rapid utilization of glucose and sharply increased the
      efficiency of its conversion to Act. From the current experiments, it is
      concluded that carbon storage metabolism plays a significant role in precursor
      supply for Act production and that manipulation of central carbohydrate
      metabolism can lead to an increased production of Act in S. coelicolor.

PMID- 16950897
TI  - Isolation and characterization of a novel lipase from a metagenomic library of
      tidal flat sediments: evidence for a new family of bacterial lipases.
AB  - We cloned lipG, which encoded a lipolytic enzyme, from a Korean tidal flat
      metagenomic library. LipG was related to six putative lipases previously
      identified only in bacterial genome sequences. These enzymes comprise a new
      family. We partially characterized LipG, providing the first experimental data
      for a member of this family.

PMID- 16950898
TI  - Survival of Wolbachia pipientis in cell-free medium.
AB  - Wolbachia pipientis is an obligate intracellular bacterium found in a wide range
      of invertebrate taxa. While over ecological timescales Wolbachia infections are
      maintained by strict maternal inheritance, horizontal transfer events are common
      over evolutionary time. To be horizontally transferred between organisms,
      Wolbachia bacteria must pass through and survive an extracellular phase. We used
      BacLight live-dead staining, PCR, and fluorescence in situ hybridization to
      assess the ability for purified Wolbachia bacteria to survive in cell-free media.
      We found that purified Wolbachia bacteria were able to survive extracellularly
      for up to 1 week with no decrease in viability. While no replication was observed
      in the extracellular phase, purified Wolbachia bacteria were able to reinvade
      cells and establish stable infections at all time points. The ability of
      Wolbachia bacteria to survive outside host cells may increase the probability of
      successful horizontal transfer and the exploitation of new ecological niches. Our
      development of methods to purify and maintain viable Wolbachia bacteria from
      cultured cells will be useful for other researchers studying Wolbachia biology.

PMID- 16950899
TI  - Polyphosphate stores enhance the ability of Vibrio cholerae to overcome
      environmental stresses in a low-phosphate environment.
AB  - Vibrio cholerae, the causative agent of Asiatic cholera, has been reported to
      make large quantities of polyphosphate. Inorganic polyphosphate is a ubiquitous
      molecule with a variety of functions in prokaryotic and eukaryotic cells. We
      constructed a V. cholerae mutant with a deletion in the polyphosphate kinase
      (ppk) gene. The mutant was defective in polyphosphate biosynthesis. Deletion of
      ppk had no significant effect on production of cholera toxin,
      hemagglutinin/protease, motility, biofilm formation, and colonization of the
      suckling mouse intestine. The wild type and mutant had similar growth rates in
      rich and minimal medium and exhibited similar phosphate uptake and alkaline
      phosphatase induction. In contrast to ppk mutants from other gram-negative
      bacteria, the V. cholerae mutant survived prolonged starvation in LB medium and
      artificial seawater basal salts. The ppk mutant was significantly more sensitive
      to low pH, high salinity, and oxidative stress when it was cultured in low
      phosphate minimal medium. The ppk mutant failed to induce catalase when it was
      downshifted to phosphorus-limiting conditions. Furthermore, the increased
      sensitivity of the ppk mutant to environmental stressors in phosphate-limited
      medium correlated with a diminished capacity to synthesize ATP from intracellular
      reservoirs. We concluded that polyphosphate protects V. cholerae from
      environmental stresses under phosphate limitation conditions. It has been
      proposed that toxigenic V. cholerae can survive in estuaries and brackish waters
      in which phosphorus and/or nitrogen can be a limiting nutrient. Thus, synthesis
      of large polyphosphate stores could enhance the ability of V. cholerae to survive
      in the aquatic environment.

PMID- 16950901
TI  - Antimicrobial susceptibilities of Aeromonas spp. isolated from environmental
      sources.
AB  - Aeromonas spp. are ubiquitous aquatic bacteria that cause serious infections in
      both poikilothermic and endothermic animals, including humans. Clinical isolates
      have shown an increasing incidence of antibiotic and antimicrobial drug
      resistance since the widespread use of antibiotics began. A total of 282
      Aeromonas pure cultures were isolated from both urban and rural playa lakes in
      the vicinity of Lubbock, Texas, and several rivers in West Texas and New Mexico.
      Of these, at least 104 were subsequently confirmed to be independent isolates.
      The 104 isolates were identified by Biolog and belonged to 11 different species.
      The MICs of six metals, one metalloid, five antibiotics, and two antimicrobial
      drugs were determined. All aeromonads were sensitive to chromate, cobalt, copper,
      nickel, zinc, cefuroxime, kanamycin, nalidixic acid, ofloxacin, tetracycline, and
      sulfamethoxazole. Low incidences of trimethoprim resistance, mercury resistance,
      and arsenite resistance were found. Dual resistances were found in 5 of the 104
      Aeromonas isolates. Greater numbers of resistant isolates were obtained from
      samples taken in March versus July 2002 and from sediment versus water. Plasmids
      were isolated from selected strains of the arsenite- and mercury-resistant
      organisms and were transformed into Escherichia coli XL1-Blue MRF'. Acquisition
      of the resistance phenotypes by the new host showed that these resistance genes
      were carried on the plasmids. Mercury resistance was found to be encoded on a
      conjugative plasmid. Despite the low incidence of resistant isolates, the six
      playa lakes and three rivers that were sampled in this study can be considered a
      reservoir for antimicrobial resistance genes.

PMID- 16950900
TI  - Diversity of basidiomycetes in michigan agricultural soils.
AB  - We analyzed the communities of soil basidiomycetes in agroecosystems that differ
      in tillage history at the Kellogg Biological Station Long-Term Ecological
      Research site near Battle Creek, Michigan. The approach combined soil DNA
      extraction through a bead-beating method modified to increase recovery of fungal
      DNA, PCR amplification with basidiomycete-specific primers, cloning and
      restriction fragment length polymorphism screening of mixed PCR products, and
      sequencing of unique clones. Much greater diversity was detected than was
      anticipated in this habitat on the basis of culture-based methods or surveys of
      fruiting bodies. With "species" defined as organisms yielding PCR products with >
      or =99% identity in the 5' 650 bases of the nuclear large-subunit ribosomal DNA,
      241 "species" were detected among 409 unique basidiomycete sequences recovered.
      Almost all major clades of basidiomycetes from basidiomycetous yeasts and other
      heterobasidiomycetes through polypores and euagarics (gilled mushrooms and
      relatives) were represented, with a majority from the latter clade. Only 24 of
      241 "species" had 99% or greater sequence similarity to named reference sequences
      in GenBank, and several clades with multiple "species" could not be identified at
      the genus level by phylogenetic comparisons with named sequences. The total
      estimated "species" richness for this 11.2-ha site was 367 "species" of
      basidiomycetes. Since >99% of the study area has not been sampled, the accuracy
      of our diversity estimate is uncertain. Replication in time and space is required
      to detect additional diversity and the underlying community structure.

PMID- 16950902
TI  - Application of pseudomurein endoisopeptidase to fluorescence in situ
      hybridization of methanogens within the family Methanobacteriaceae.
AB  - In situ detection of methanogens within the family Methanobacteriaceae is
      sometimes known to be unsuccessful due to the difficulty in permeability of
      oligonucleotide probes. Pseudomurein endoisopeptidase (Pei), a lytic enzyme that
      specifically acts on their cell walls, was applied prior to 16S rRNA-targeting
      fluorescence in situ hybridization (FISH). For this purpose, pure cultured
      methanogens within this family, Methanobacterium bryantii, Methanobrevibacter
      ruminantium, Methanosphaera stadtmanae, and Methanothermobacter
      thermautotrophicus together with a Methanothermobacter thermautotrophicus
      containing syntrophic acetate-oxidizing coculture, endosymbiotic
      Methanobrevibacter methanogens within an anaerobic ciliate, and an upflow
      anaerobic sludge blanket (UASB) granule were examined. Even without the Pei
      treatment, Methanobacterium bryantii and Methanothermobacter thermautotrophicus
      cells are relatively well hybridized with oligonucleotide probes. However, almost
      none of the cells of Methanobrevibacter ruminantium, Methanosphaera stadtmanae,
      cocultured Methanothermobacter thermautotrophicus, and the endosymbiotic
      methanogens and the cells within UASB granule were hybridized. Pei treatment was
      able to increase the probe hybridization ratio in every specimen, particularly in
      the specimen that had shown little hybridization. Interestingly, the hybridizing
      signal intensity of Methanothermobacter thermautotrophicus cells in coculture
      with an acetate-oxidizing H(2)-producing syntroph was significantly improved by
      Pei pretreatment, whereas the probe was well hybridized with the cells of pure
      culture of the same strain. We found that the difference is attributed to the
      differences in cell wall thicknesses between the two culture conditions. These
      results indicate that Pei treatment is effective for FISH analysis of methanogens
      that show impermeability to the probe.

PMID- 16950903
TI  - Diversity and distribution of Escherichia coli genotypes and antibiotic
      resistance phenotypes in feces of humans, cattle, and horses.
AB  - Escherichia coli is the most completely characterized prokaryotic model organism
      and one of the dominant indicator organisms for food and water quality testing,
      yet comparatively little is known about the structure of E. coli populations in
      their various hosts. The diversities of E. coli populations isolated from the
      feces of three host species (human, cow, and horse) were compared by two
      subtyping methods: ribotyping (using HindIII) and antibiotic resistance analysis
      (ARA). The sampling effort required to obtain a representative sample differed by
      host species, as E. coli diversity was consistently greatest in horses, followed
      by cattle, and was lowest in humans. The diversity of antibiotic resistance
      patterns isolated from individuals was consistently greater than the diversity of
      ribotypes. E. coli populations in individuals sampled monthly, over a 7- to 8
      month period, were highly variable in terms of both ribotypes and ARA phenotypes.
      In contrast, E. coli populations in cattle and humans were stable over an 8-h
      period. Following the cessation of antibiotic therapy, the E. coli population in
      the feces of one human experienced a rapid and substantial shift, from a multiply
      antibiotic-resistant phenotype associated with a particular ribotype to a
      relatively antibiotic-susceptible phenotype associated with a different ribotype.
      The high genetic diversity of E. coli populations, differences in diversity among
      hosts, and temporal variability all indicate complex population dynamics that
      influence the usefulness of E. coli as a water quality indicator and its use in
      microbial source tracking studies.

PMID- 16950904
TI  - Advantage of using inosine at the 3' termini of 16S rRNA gene universal primers
      for the study of microbial diversity.
AB  - To overcome the shortcomings of universal 16S rRNA gene primers 8F and 907R when
      studying the diversity of complex microbial communities, the 3' termini of both
      primers were replaced with inosine. A comparison of the clone libraries derived
      using both primer sets showed seven bacterial phyla amplified by the altered
      primer set (8F-I/907R-I) whereas the original set amplified sequences belonging
      almost exclusively to Proteobacteria (95.8%). Sequences belonging to Firmicutes
      (42.6%) and Thermotogae (9.3%) were more abundant in a library obtained by using
      8F-I/907R-I at a PCR annealing temperature of 54 degrees C, while Proteobacteria
      sequences were more frequent (62.7%) in a library obtained at 50 degrees C,
      somewhat resembling the result obtained using the original primer set. The
      increased diversity revealed by using primers 8F-I/907R-I confirms the usefulness
      of primers with inosine at the 3' termini in studying the microbial diversity of
      environmental samples.

PMID- 16950905
TI  - Quantitative detection of Corynebacterium casei in cheese by real-time PCR.
AB  - The flora on the surface of smear-ripened cheeses is composed of numerous species
      of bacteria and yeasts that contribute to the production of the desired
      organoleptic properties. Due to the absence of selective media, it is very
      difficult to quantify cheese surface bacteria, and, consequently, the ecology of
      the cheese surface microflora has not been extensively investigated. We developed
      a SYBR green I real-time PCR method to quantify Corynebacterium casei, a major
      species of smear-ripened cheeses, using primers designed to target the 16S rRNA
      gene. It was possible to recover C. casei genomic DNA from the cheese matrix with
      nearly the same yield that C. casei genomic DNA is recovered from cells recovered
      by centrifugation from liquid cultures. Quantification was linear over a range
      from 10(5) to 10(10) CFU per g of cheese. The specificity of the assay was
      demonstrated with DNA from species related to C. casei and from other bacteria
      and yeasts belonging to the cheese flora. Nine commercial cheeses were analyzed
      by real-time PCR, and six of them were found to contain more than 10(5) CFU
      equivalents of C. casei per g. In two of them, the proportion of C. casei in the
      total bacterial flora was nearly 40%. The presence of C. casei in these samples
      was further confirmed by single-strand conformation polymorphism analysis and by
      a combined approach consisting of plate counting and 16S rRNA gene sequencing. We
      concluded that SYBR green I real-time PCR may be used as a reliable species
      specific method for quantification of bacteria from the surface of cheeses.

PMID- 16950906
TI  - Phylogenetic comparisons of bacterial communities from serpentine and
      nonserpentine soils.
AB  - I present the results of a culture-independent survey of soil bacterial
      communities from serpentine soils and adjacent nonserpentine comparator soils
      using a variety of newly developed phylogenetically based statistical tools. The
      study design included site-based replication of the serpentine-to-nonserpentine
      community comparison over a regional scale ( approximately 100 km) in Northern
      California and Southern Oregon by producing 16S rRNA clone libraries from pairs
      of samples taken on either side of the serepentine-nonserpentine edaphic boundary
      at three geographical sites. At the division level, the serpentine and
      nonserpentine communities were similar to each other and to previous data from
      forest soils. Comparisons of both richness and Shannon diversity produced no
      significant differences between any of the libraries, but the vast majority of
      phylogenetically based tests were significant, even with only 50 sequences per
      library. These results suggest that most samples were distinct, consisting of a
      collection of lineages generally not found in other samples. The pattern of
      results showed that serpentine communities tended to be more similar to each
      other than they were to nonserpentine communities, and these differences were at
      a lower taxonomic scale. Comparisons of two nonserpentine communities generally
      showed differences, and some results suggest that the geographical site may
      control community composition as well. These results show the power of
      phylogenetic tests to discern differences between 16S rRNA libraries compared to
      tests that discard DNA data to bin sequences into operational taxonomic units,
      and they stress the importance of replication at larger scales for inferences
      regarding microbial biogeography.

PMID- 16950907
TI  - Interspecific transfer of bacterial endosymbionts between tsetse fly species:
      infection establishment and effect on host fitness.
AB  - Tsetse flies (Glossina spp.) can harbor up to three distinct species of
      endosymbiotic bacteria that exhibit unique modes of transmission and evolutionary
      histories with their host. Two mutualist enterics, Wigglesworthia and Sodalis,
      are transmitted maternally to tsetse flies' intrauterine larvae. The third
      symbiont, from the genus Wolbachia, parasitizes developing oocytes. In this
      study, we determined that Sodalis isolates from several tsetse fly species are
      virtually identical based on a phylogenetic analysis of their ftsZ gene
      sequences. Furthermore, restriction fragment-length polymorphism analysis
      revealed little variation in the genomes of Sodalis isolates from tsetse fly
      species within different subgenera (Glossina fuscipes fuscipes and Glossina
      morsitans morsitans). We also examined the impact on host fitness of
      transinfecting G. fuscipes fuscipes and G. morsitans morsitans flies with
      reciprocal Sodalis strains. Tsetse flies cleared of their native Sodalis
      symbionts were successfully repopulated with the Sodalis species isolated from a
      different tsetse fly species. These transinfected flies effectively transmitted
      the novel symbionts to their offspring and experienced no detrimental fitness
      effects compared to their wild-type counterparts, as measured by longevity and
      fecundity. Quantitative PCR analysis revealed that transinfected flies maintained
      their Sodalis populations at densities comparable to those in flies harboring
      native symbionts. Our ability to transinfect tsetse flies is indicative of
      Sodalis ' recent evolutionary history with its tsetse fly host and demonstrates
      that this procedure may be used as a means of streamlining future
      paratransgenesis experiments.

PMID- 16950908
TI  - Essentiality of a newly identified carbohydrate-binding module for the function
      of CelB (BH0603) from the alkaliphilic bacterium Bacillus halodurans.
AB  - CelB (BH0603) from Bacillus halodurans is a modular glycoside hydrolase with a
      family 5 catalytic module, an immunoglobulin-like module, and module PfamB of
      unknown function. The recombinant PfamB module bound to Avicel and was essential
      for CelB hydrolytic function. We propose that module PfamB be designated a new
      carbohydrate-binding module.

PMID- 16950909
TI  - Biotransformation of N-nitrosodimethylamine by Pseudomonas mendocina KR1.
AB  - N-Nitrosodimethylamine (NDMA) is a potent carcinogen and an emerging contaminant
      in groundwater and drinking water. The metabolism of NDMA in mammalian cells has
      been widely studied, but little information is available concerning the microbial
      transformation of this compound. The objective of this study was to elucidate the
      pathway(s) of NDMA biotransformation by Pseudomonas mendocina KR1, a strain that
      possesses toluene-4-monooxygenase (T4MO). P. mendocina KR1 was observed to
      initially oxidize NDMA to N-nitrodimethylamine (NTDMA), a novel metabolite. The
      use of 18O2 and H(2)18O revealed that the oxygen added to NDMA to produce NTDMA
      was derived from atmospheric O2. Experiments performed with a pseudomonad
      expressing cloned T4MO confirmed that T4MO catalyzes this initial reaction. The
      NTDMA produced by P. mendocina KR1 did not accumulate, but rather it was
      metabolized further to produce N-nitromethylamine (88 to 94% recovery) and a
      trace amount of formaldehyde (HCHO). Small quantities of methanol (CH3OH) were
      also detected when the strain was incubated with NDMA but not during incubation
      with either NTDMA or HCHO. The formation of methanol is hypothesized to occur via
      a second, minor pathway mediated by an initial alpha-hydroxylation of the
      nitrosamine. Strain KR1 did not grow on NDMA or mineralize significant quantities
      of the compound to carbon dioxide, suggesting that the degradation process is
      cometabolic.

PMID- 16950910
TI  - In vivo insertional mutagenesis in Corynebacterium pseudotuberculosis: an
      efficient means to identify DNA sequences encoding exported proteins.
AB  - The reporter transposon-based system TnFuZ was used to identify exported proteins
      of the animal pathogen Corynebacterium pseudotuberculosis. Thirty-four out of
      1,500 mutants had detectable alkaline phosphatase (PhoZ) activity. This activity
      was from 21 C. pseudotuberculosis loci that code for fimbrial and transport
      subunits and for hypothetical and unknown-function proteins.

PMID- 16950911
TI  - Changes in active bacterial communities before and after dredging of highly
      polluted Baltic Sea sediments.
AB  - Bacteria residing in sediments have key functions in the marine food web.
      However, it has been difficult to correlate the identity and activity of bacteria
      in sediments due to lack of appropriate methods beyond cultivation-based
      techniques. Our aim was to use a combination of molecular approaches,
      bromodeoxyuridine incorporation and immunocapture, terminal restriction fragment
      length polymorphism, and cloning and sequencing of 16S rRNA genes to assess the
      composition of growing bacteria in Baltic Sea sediments. The study site was a
      highly polluted area off the Swedish coast. The sediments were sampled in two
      consecutive years, before and after remediation, by dredging of the top
      sediments. Levels of polyaromatic hydrocarbons (PAHs), mercury, and
      polychlorinated biphenyls were dramatically reduced as a result of the cleanup
      project. The compositions of growing members of the communities were
      significantly different at the two sampling periods. In particular, members from
      the class Deltaproteobacteria and genus Spirochaeta were more dominant before
      dredging, but members of the classes Gammaproteobacteria and the Flavobacteria
      represented the most dominant growing populations after dredging. We also
      cultivated isolates from the polluted sediments that could transform the model
      PAH compound, phenanthrene. Some of these isolates were confirmed as dominant
      growing populations by the molecular methods as well. This suite of methods
      enabled us to link the identity and activity of the members of the sediment
      communities.

PMID- 16950912
TI  - Quantifying substrate uptake by individual cells of marine bacterioplankton by
      catalyzed reporter deposition fluorescence in situ hybridization combined with
      microautoradiography.
AB  - Catalyzed reporter deposition fluorescence in situ hybridization combined with
      microautoradiography (MICRO-CARD-FISH) is increasingly being used to obtain
      qualitative information on substrate uptake by individual members of specific
      prokaryotic communities. Here we evaluated the potential for using this approach
      quantitatively by relating the measured silver grain area around cells taking up
      (3)H-labeled leucine to bulk leucine uptake measurements. The increase in the
      silver grain area over time around leucine-assimilating cells of coastal
      bacterial assemblages was linear during 4 to 6 h of incubation. By establishing
      standardized conditions for specific activity levels and concomitantly performing
      uptake measurements with the bulk community, MICRO-CARD-FISH can be used
      quantitatively to determine uptake rates on a single-cell level. Therefore, this
      approach allows comparisons of single-cell activities for bacterial communities
      obtained from different sites or growing under different ecological conditions.

PMID- 16950913
TI  - Use of optical density detection times to assess the effect of acetic acid on
      single-cell kinetics.
AB  - The growth of Listeria innocua at different acetic acid concentrations (0 to
      2,000 ppm) was monitored by optical density measurements in a Bioscreen
      (Labsystems, Vantaa, Finland). The generated populations came from low inocula
      that were obtained by serial dilution. A new method to estimate both the growth
      rate and the lag time of single cells from the detection times (time to reach an
      optical density of 0.11) was developed. It assumes that the single-cell lag times
      follow a gamma distribution and takes into account the randomness of the
      inoculation level. (The initial cell number per well was assumed to follow a
      Poisson distribution.) In this way, relatively small numbers of replicates are
      sufficient to obtain a robust estimation of the distribution of single-cell lag
      times. The results were validated with plate count experiments. It was found that
      logarithms of both the growth rates and of population lag times increased
      linearly with the acetic acid concentration. The logarithm of the scale parameter
      of the gamma distribution of the single-cell lag times also increased linearly
      with the acetic acid concentration irrespective of the phase of the inoculum.

PMID- 16950914
TI  - Response of the microaerophilic Bifidobacterium species, B. boum and B.
      thermophilum, to oxygen.
AB  - We investigated the effects of O2 on Bifidobacterium species using liquid shaking
      cultures under various O2 concentrations. Although most of the Bifidobacterium
      species we selected showed O2 sensitivity, two species, B. boum and B.
      thermophilum, demonstrated microaerophilic profiles. The growth of B. bifidum and
      B. longum was inhibited under high-O2 conditions accompanied by the accumulation
      of H2O2 in the medium, and growth was restored by adding catalase to the medium.
      B. boum and B. thermophilum grew well even under 20% O2 conditions without H2O2
      accumulation, and growth was stimulated compared to anoxic growth. H2O-forming
      NADH oxidase activities were detected dominantly in cell extracts of B. boum and
      B. thermophilum under acidic reaction conditions (pH 5.0 to 6.0).

PMID- 16950915
TI  - Symbiotic bacteria associated with stomach discs of human lice.
AB  - The symbiotic bacteria associated with the stomach disc, a large aggregate of
      bacteriocytes on the ventral side of the midgut, of human body and head lice were
      characterized. Molecular phylogenetic analysis of 16S rRNA gene sequences showed
      that the symbionts formed a distinct and well-defined clade in the
      Gammaproteobacteria. The sequences exhibited AT-biased nucleotide composition and
      accelerated molecular evolution. In situ hybridization revealed that in nymphs
      and adult males, the symbiont was localized in the stomach disc, while in adult
      females, the symbiont was not in the stomach disc but in the lateral oviducts and
      the posterior pole of the oocytes due to female-specific symbiont migration. We
      propose the designation "Candidatus Riesia pediculicola" for the louse symbionts.

PMID- 16950916
TI  - Interaction between coat morphogenetic proteins SafA and SpoVID.
AB  - Morphogenetic proteins such as SpoVID and SafA govern assembly of the Bacillus
      subtilis endospore coat by guiding the various protein structural components to
      the surface of the developing spore. Previously, a screen for peptides able to
      interact with SpoVID led to the identification of a PYYH motif present in the C
      terminal half of the SafA protein and to the subsequent demonstration that SpoVID
      and SafA directly interact. spoVID and safA spores show deficiencies in coat
      assembly and are lysozyme susceptible. Both proteins, orthologs of which are
      found in all Bacillus species, have LysM domains for peptidoglycan binding and
      localize to the cortex-coat interface. Here, we show that the interaction between
      SafA and SpoVID involves the PYYH motif (region B) but also a 13-amino-acid
      region (region A) just downstream of the N-terminal LysM domain of SafA. We show
      that deletion of region B does not block the interaction of SafA with SpoVID, nor
      does it bring about spore susceptibility to lysozyme. Nevertheless, it appears to
      reduce the interaction and affects the complex. In contrast, lesions in region A
      impaired the interaction of SafA with SpoVID in vitro and, while not affecting
      the accumulation of SafA in vivo, interfered with the localization of SafA around
      the developing spore, causing aberrant assembly of the coat and lysozyme
      sensitivity. A peptide corresponding to region A interacts with SpoVID,
      suggesting that residues within this region directly contact SpoVID. Since region
      A is highly conserved among SafA orthologs, this motif may be an important
      determinant of coat assembly in the group of Bacillus spore formers.

PMID- 16950917
TI  - Identification and characterization of bicistronic speB and prsA gene expression
      in the group A Streptococcus.
AB  - Severe, invasive group A streptococcal infections have reemerged worldwide, and
      extracellular toxins, including streptococcal pyrogenic exotoxin B (SpeB), have
      been implicated in pathogenesis. The genetic regulation of SpeB is not fully
      understood, and the mechanisms involved in the processing of the protoxin to its
      enzymatically active form have not been definitively established. The present
      work demonstrated that the genes encoding SpeB (speB) and a peptidyl-prolyl
      isomerase (prsA) constitute an operon with transcription initiated from two
      promoters upstream of speB. Further, the speB-prsA operon was transcribed as a
      bicistronic mRNA. This finding is in contrast to the generally accepted notion
      that speB is transcribed only as a monocistronic gene. In addition, prsA has its
      own promoter, and transcription from this promoter starts in early log phase,
      prior to the transcription of speB. Genomic disruption of prsA decreased the
      production of enzymatically active SpeB but not the level of the pro-SpeB
      zymogen. Taken together, these results demonstrate that prsA is required for
      production of fully mature, enzymatically active SpeB.

PMID- 16950918
TI  - The dps gene of symbiotic "Candidatus Legionella jeonii" in Amoeba proteus
      responds to hydrogen peroxide and phagocytosis.
AB  - To survive in host cells, intracellular pathogens or symbiotic bacteria require
      protective mechanisms to overcome the oxidative stress generated by phagocytic
      activities of the host. By genomic library tagging, we cloned a dps (stands for
      DNA-binding protein from starved cells) gene of the symbiotic "Candidatus
      Legionella jeonii" organism (called the X bacterium) (dps(X)) that grows in
      Amoeba proteus. The gene encodes a 17-kDa protein (pI 5.19) with 91% homology to
      Dps and DNA-binding ferritin-like proteins of other organisms. The cloned gene
      complemented the dps mutant of Escherichia coli and conferred resistance to
      hydrogen peroxide. Dps(X) proteins purified from E. coli transformed with the
      dps(X) gene were in oligomeric form, formed a complex with pBlueskript SKII DNA,
      and protected the DNA from DNase I digestion and H(2)O(2)-mediated damage. The
      expression of the dps(X) gene in "Candidatus Legionella jeonii" was enhanced when
      the host amoeba was treated with 2 mM H(2)O(2) and by phagocytic activities of
      the host cell. These results suggested that the Dps protein has a function
      protective of the bacterial DNA and that its gene expression responds to
      oxidative stress generated by phagocytic activities of the host cell. With regard
      to the fact that invasion of Legionella sp. into respiratory phagocytic cells
      causes pneumonia in mammals, further characterization of dps(X) expression in the
      Legionella sp. that multiplies in a protozoan host in the natural environment may
      provide valuable information toward understanding the protective mechanisms of
      intracellular pathogens.

PMID- 16950919
TI  - The cytotoxic fimbrial structural subunit of Xenorhabdus nematophila is a pore
      forming toxin.
AB  - We have purified a fimbrial shaft protein (MrxA) of Xenorhabdus nematophila. The
      soluble monomeric protein lysed larval hemocytes of Helicoverpa armigera. Osmotic
      protection of the cells with polyethylene glycol suggested that the 17-kDa MrxA
      subunit makes pores in the target cell membrane. The internal diameter of the
      pores was estimated to be >2.9 nm. Electron microscopy confirmed the formation of
      pores by the fimbrial subunit. MrxA protein oligomerized in the presence of
      liposomes. Electrophysiological studies demonstrated that MrxA formed large,
      voltage-gated passive-diffusion channels in lipid bilayers.

PMID- 16950920
TI  - Escherichia coli pfs transcription: regulation and proposed roles in autoinducer
      2 synthesis and purine excretion.
AB  - Pfs expression is required for several metabolic pathways and limits the
      production of autoinducer-2, a molecule proposed to play a central role in
      interspecies quorum sensing. The present study reveals physiological conditions
      and promoter DNA elements that regulate Escherichia coli pfs transcription. Pfs
      transcription is shown to rely on both sigma 70 and sigma 38 (rpoS), and the
      latter is subject to induction that increases pfs expression. Transcription is
      maximal as the cells approach stationary phase, and this level can be increased
      by salt stress through induction of sigma 38-dependent expression. The pfs
      promoter is shown to contain both positive and negative elements, which can be
      used by both forms of RNA polymerase. The negative element is contained within
      the overlapping dgt promoter, which is involved in purine metabolism.
      Consideration of the physiological roles of sigma 38 and dgt leads to a model for
      how autoinducer production is controlled under changing physiological conditions.

PMID- 16950921
TI  - Novel role of mfd: effects on stationary-phase mutagenesis in Bacillus subtilis.
AB  - Previously, using a chromosomal reversion assay system, we established that an
      adaptive mutagenic process occurs in nongrowing Bacillus subtilis cells under
      stress, and we demonstrated that multiple mechanisms are involved in generating
      these mutations (41, 43). In an attempt to delineate how these mutations are
      generated, we began an investigation into whether or not transcription and
      transcription-associated proteins influence adaptive mutagenesis. In B. subtilis,
      the Mfd protein (transcription repair coupling factor) facilitates removal of RNA
      polymerase stalled at transcriptional blockages and recruitment of repair
      proteins to DNA lesions on the transcribed strand. Here we demonstrate that the
      loss of Mfd has a depressive effect on stationary-phase mutagenesis. An
      association between Mfd mutagenesis and aspects of transcription is discussed.

PMID- 16950922
TI  - The Streptomyces NrdR transcriptional regulator is a Zn ribbon/ATP cone protein
      that binds to the promoter regions of class Ia and class II ribonucleotide
      reductase operons.
AB  - Ribonucleotide reductases (RNRs) catalyze the conversion of ribonucleotides to
      deoxyribonucleotides and are essential for de novo DNA synthesis and repair.
      Streptomyces spp. contain genes coding for two RNRs, either of which is
      sufficient for vegetative growth. The class Ia RNR is encoded by the nrdAB genes,
      and the class II RNR is encoded by nrdJ, which is coexpressed with nrdR. We
      previously showed that the Streptomyces coelicolor nrdR gene encodes a protein,
      NrdR, which represses transcription of both sets of RNR genes. NrdR is a member
      of a highly conserved family of proteins that is confined exclusively to
      prokaryotes. In this report, we describe a physical and biochemical
      characterization of the S. coelicolor NrdR protein and show that it is a zinc
      ATP/dATP-containing protein that binds to the promoter regions of both
      Streptomyces RNR operons. The NrdR N terminus contains a zinc ribbon motif that
      is necessary for binding to the upstream regulatory region of both RNR operons.
      The latter contains two 16-bp direct repeat sequences, termed NrdR boxes, which
      are located proximal to, or overlap with, the promoter regions. These experiments
      support the view that NrdR controls the transcription of RNR genes by binding to
      the NrdR box sequences. We also show that the central NrdR ATP cone domain binds
      ATP and dATP and that mutations that abolish ATP/dATP binding significantly
      reduce DNA binding, suggesting that the ATP cone domain may allosterically
      regulate NrdR binding. We conclude that NrdR is a widely conserved regulator of
      RNR genes, binding to specific sequence elements in the promoter region and
      thereby modulating transcription.

PMID- 16950923
TI  - Posttranslational modification of the 20S proteasomal proteins of the archaeon
      Haloferax volcanii.
AB  - 20S proteasomes are large, multicatalytic proteases that play an important role
      in intracellular protein degradation. The barrel-like architecture of 20S
      proteasomes, formed by the stacking of four heptameric protein rings, is highly
      conserved from archaea to eukaryotes. The outer two rings are composed of alpha
      type subunits, and the inner two rings are composed of beta-type subunits. The
      halophilic archaeon Haloferax volcanii synthesizes two different alpha-type
      proteins, alpha1 and alpha2, and one beta-type protein that assemble into at
      least two 20S proteasome subtypes. In this study, we demonstrate that all three
      of these 20S proteasomal proteins (alpha1, alpha2, and beta) are modified either
      post- or cotranslationally. Using electrospray ionization quadrupole time-of
      flight mass spectrometry, a phosphorylation site of the beta subunit was
      identified at Ser129 of the deduced protein sequence. In addition, alpha1 and
      alpha2 contained N-terminal acetyl groups. These findings represent the first
      evidence of acetylation and phosphorylation of archaeal proteasomes and are one
      of the limited examples of post- and/or cotranslational modification of proteins
      in this unusual group of organisms.

PMID- 16950924
TI  - TOS9 regulates white-opaque switching in Candida albicans.
AB  - In Candida albicans, the a1-alpha2 complex represses white-opaque switching, as
      well as mating. Based upon the assumption that the a1-alpha2 corepressor complex
      binds to the gene that regulates white-opaque switching, a
      chromatinimmunoprecipitation-microarray analysis strategy was used to identify 52
      genes that bound to the complex. One of these genes, TOS9, exhibited an
      expression pattern consistent with a "master switch gene." TOS9 was only
      expressed in opaque cells, and its gene product, Tos9p, localized to the nucleus.
      Deletion of the gene blocked cells in the white phase, misexpression in the white
      phase caused stable mass conversion of cells to the opaque state, and
      misexpression blocked temperature-induced mass conversion from the opaque state
      to the white state. A model was developed for the regulation of spontaneous
      switching between the opaque state and the white state that includes stochastic
      changes of Tos9p levels above and below a threshold that induce changes in the
      chromatin state of an as-yet-unidentified switching locus. TOS9 has also been
      referred to as EAP2 and WOR1.

PMID- 16950925
TI  - Specific inhibition of the plasmodial surface anion channel by dantrolene.
AB  - The plasmodial surface anion channel (PSAC), induced on human erythrocytes by the
      malaria parasite Plasmodium falciparum, is an important target for antimalarial
      drug development because it may contribute to parasite nutrient acquisition.
      However, known antagonists of this channel are quite nonspecific, inhibiting many
      other channels and carriers. This lack of specificity not only complicates drug
      development but also raises doubts about the exact role of PSAC in the well-known
      parasite-induced permeability changes. We recently identified a family of new
      PSAC antagonists structurally related to dantrolene, an antagonist of muscle Ca++
      release channels. Here, we explored the mechanism of dantrolene's actions on
      parasite-induced permeability changes. We found that dantrolene inhibits the
      increased permeabilities of sorbitol, two amino acids, an organic cation, and
      hypoxanthine, suggesting a common pathway shared by these diverse solutes. It
      also produced parallel reductions in PSAC single-channel and whole-cell Cl-
      currents. In contrast to its effect on parasite-induced permeabilities,
      dantrolene had no measurable effect on five other classes of anion channels,
      allaying concerns of poor specificity inherent to other known antagonists. Our
      studies indicate that dantrolene binds PSAC at an extracellular site distinct
      from the pore, where it inhibits the conformational changes required for channel
      gating. Its affinity for this site depends on ionic strength, implicating
      electrostatic interactions in dantrolene binding. In addition to the potential
      therapeutic applications of its derivatives, dantrolene's specificity and its
      defined mechanism of action on PSAC make it a useful tool for transport studies
      of infected erythrocytes.

PMID- 16950926
TI  - RacG regulates morphology, phagocytosis, and chemotaxis.
AB  - RacG is an unusual member of the complex family of Rho GTPases in Dictyostelium.
      We have generated a knockout (KO) strain, as well as strains that overexpress
      wild-type (WT), constitutively active (V12), or dominant negative (N17) RacG. The
      protein is targeted to the plasma membrane, apparently in a nucleotide-dependent
      manner, and induces the formation of abundant actin-driven filopods. RacG is
      enriched at the rim of the progressing phagocytic cup, and overexpression of RacG
      WT or RacG-V12 induced an increased rate of particle uptake. The positive effect
      of RacG on phagocytosis was abolished in the presence of 50 microM LY294002, a
      phosphoinositide 3-kinase inhibitor, indicating that generation of
      phosphatidylinositol 3,4,5-trisphosphate is required for activation of RacG. RacG
      KO cells showed a moderate chemotaxis defect that was stronger in the RacG-V12
      and RacG-N17 mutants, in part because of interference with signaling through
      Rac1. The in vivo effects of RacG-V12 could not be reproduced by a mutant lacking
      the Rho insert region, indicating that this region is essential for interaction
      with downstream components. Processes like growth, pinocytosis, exocytosis,
      cytokinesis, and development were unaffected in Rac-KO cells and in the
      overexpressor mutants. In a cell-free system, RacG induced actin polymerization
      upon GTPgammaS stimulation, and this response could be blocked by an Arp3
      antibody. While the mild phenotype of RacG-KO cells indicates some overlap with
      one or more Dictyostelium Rho GTPases, like Rac1 and RacB, the significant
      changes found in overexpressors show that RacG plays important roles. We
      hypothesize that RacG interacts with a subset of effectors, in particular those
      concerned with shape, motility, and phagocytosis.

PMID- 16950927
TI  - Glutathione reductase and a mitochondrial thioredoxin play overlapping roles in
      maintaining iron-sulfur enzymes in fission yeast.
AB  - In the fission yeast Schizosaccharomyces pombe, the pgr1+ gene encoding
      glutathione (GSH) reductase (GR) is essentially required for cell survival.
      Depletion of GR caused proliferation arrest at the G1 phase of the cell cycle
      under aerobic conditions. Multicopy suppressors that restore growth were
      screened, and one effective suppressor was found to be the trx2+ gene, encoding a
      mitochondrial thioredoxin. This suggests that GR is critically required for some
      mitochondrial function(s). We found that GR resides in both cytosolic and
      organellar fractions of the cell. Depletion of GR lowered the respiration rate
      and the activity of oxidation-labile Fe-S enzymes such as mitochondrial aconitase
      and cytosolic sulfite reductase. Trx2 did not reverse the high ratio of oxidized
      glutathione to GSH or the low respiration rate observed in GR-depleted cells.
      However, it brought the activity of oxidation-labile Fe-S enzymes to a normal
      level, suggesting that the maintenance of Fe-S enzymes is a critical factor in
      the survival of S. pombe. The activity of succinate dehydrogenase, an oxidation
      insensitive Fe-S enzyme, however, was not affected by GR depletion, suggesting
      that GR is not required for the biogenesis of the Fe-S cluster. The total iron
      content was greatly increased by GR depletion and was brought to a nearly normal
      level by Trx2. These results indicate that the essentiality of GR in the aerobic
      growth of S. pombe is derived from its role in maintaining oxidation-labile Fe-S
      enzymes and iron homeostasis.

PMID- 16950929
TI  - The SH3/PH domain protein AgBoi1/2 collaborates with the Rho-type GTPase AgRho3
      to prevent nonpolar growth at hyphal tips of Ashbya gossypii.
AB  - Unlike most other cells, hyphae of filamentous fungi permanently elongate and
      lack nonpolar growth phases. We identified AgBoi1/2p in the filamentous
      ascomycete Ashbya gossypii as a component required to prevent nonpolar growth at
      hyphal tips. Strains lacking AgBoi1/2p frequently show spherical enlargement at
      hyphal tips with concomitant depolarization of actin patches and loss of tip
      located actin cables. These enlarged tips can repolarize and resume hyphal tip
      extension in the previous polarity axis. AgBoi1/2p permanently localizes to
      hyphal tips and transiently to sites of septation. Only the tip localization is
      important for sustained elongation of hyphae. In a yeast two-hybrid experiment,
      we identified the Rho-type GTPase AgRho3p as an interactor of AgBoi1/2p. AgRho3p
      is also required to prevent nonpolar growth at hyphal tips, and strains deleted
      for both AgBOI1/2 and AgRHO3 phenocopied the respective single-deletion strains,
      demonstrating that AgBoi1/2p and AgRho3p function in a common pathway. Monitoring
      the polarisome of growing hyphae using AgSpa2p fused to the green fluorescent
      protein as a marker, we found that polarisome disassembly precedes the onset of
      nonpolar growth in strains lacking AgBoi1/2p or AgRho3p. AgRho3p locked in its
      GTP-bound form interacts with the Rho-binding domain of the polarisome-associated
      formin AgBni1p, implying that AgRho3p has the capacity to directly activate
      formin-driven actin cable nucleation. We conclude that AgBoi1/2p and AgRho3p
      support polarisome-mediated actin cable formation at hyphal tips, thereby
      ensuring permanent polar tip growth.

PMID- 16950928
TI  - Expressed in the yeast Saccharomyces cerevisiae, human ERK5 is a client of the
      Hsp90 chaperone that complements loss of the Slt2p (Mpk1p) cell integrity stress
      activated protein kinase.
AB  - ERK5 is a mitogen-activated protein (MAP) kinase regulated in human cells by
      diverse mitogens and stresses but also suspected of mediating the effects of a
      number of oncogenes. Its expression in the slt2Delta Saccharomyces cerevisiae
      mutant rescued several of the phenotypes caused by the lack of Slt2p (Mpk1p) cell
      integrity MAP kinase. ERK5 is able to provide this cell integrity MAP kinase
      function in yeast, as it is activated by the cell integrity signaling cascade
      that normally activates Slt2p and, in its active form, able to stimulate at least
      one key Slt2p target (Rlm1p, the major transcriptional regulator of cell wall
      genes). In vitro ERK5 kinase activity was abolished by Hsp90 inhibition. ERK5
      activity in vivo was also lost in a strain that expresses a mutant Hsp90
      chaperone. Therefore, human ERK5 expressed in yeast is an Hsp90 client, despite
      the widely held belief that the protein kinases of the MAP kinase class are non
      Hsp90-dependent activities. Two-hybrid and protein binding studies revealed that
      strong association of Hsp90 with ERK5 requires the dual phosphorylation of the
      TEY motif in the MAP kinase activation loop. These phosphorylations, at positions
      adjacent to the Hsp90-binding surface recently identified for a number of protein
      kinases, may cause a localized rearrangement of this MAP kinase region that leads
      to creation of the Hsp90-binding surface. Complementation of the slt2Delta yeast
      defect by ERK5 expression establishes a new tool with which to screen for novel
      agonists and antagonists of ERK5 signaling as well as for isolating mutant forms
      of ERK5.

PMID- 16950931
TI  - Dental CAD/CAM systems: a 20-year success story.

PMID- 16950930
TI  - Cch1 mediates calcium entry in Cryptococcus neoformans and is essential in low
      calcium environments.
AB  - The ability of Cryptococcus neoformans to grow at the mammalian body temperature
      (37 degrees C to 39 degrees C) is a well-established virulence factor. Growth of
      C. neoformans at this physiological temperature requires calcineurin, a
      Ca(2+)/calmodulin-dependent protein phosphatase. When cytosolic calcium
      concentrations are low ( approximately 50 to 100 nM), calcineurin is inactive and
      becomes active only when cytosolic calcium concentrations rise ( approximately 1
      to 10 microM) through the activation of calcium channels. In this study we
      analyzed the function of Cch1 in C. neoformans and found that Cch1 is a Ca(2+)
      permeable channel that mediates calcium entry in C. neoformans. Analysis of the
      Cch1 protein sequence revealed differences in the voltage sensor (S4 regions),
      suggesting that Cch1 may have diminished voltage sensitivity or possibly an
      alternative gating mechanism. The inability of the cch1 mutant to grow under
      conditions of limited extracellular calcium concentrations
      ([Ca(2+)](extracellular), approximately 100 nM) suggested that Cch1 was required
      for calcium uptake in low-calcium environments. These results are consistent with
      the role of ScCch1 in mediating high-affinity calcium uptake in Saccharomyces
      cerevisiae. Although the growth defect of the cch1 mutant under conditions of
      limited [Ca(2+)](extracellular) ( approximately 100 nM) became more severe with
      increasing temperature (25 degrees C to 38.5 degrees ), this temperature
      sensitivity was not observed when the cch1 mutant was grown on rich medium
      ([Ca(2+)](extracellular), approximately 0.140 mM). Accordingly, the cch1 mutant
      strain displayed only attenuated virulence when tested in the mouse inhalation
      model of cryptococcosis, further suggesting that C. neoformans may have a limited
      requirement for Cch1 and that this requirement appears to include ion stress
      tolerance.

PMID- 16950932
TI  - The evolution of the CEREC system.
AB  - BACKGROUND AND OVERVIEW: Early in 1980, the author anticipated the attraction of
      restoring posterior teeth with tooth-colored material. He conducted studies and
      developed the clinical concept of bonded ceramic inlays, at the same time raising
      the issue of the fast fabrication of the ceramic restorations. The author
      developed plans for in-office computer-aided design/computer-aided manufacturing
      (CAD/CAM) fabrication of ceramic restorations specifically to enable the dentist
      to complete one or multiple ceramic restorations chairside, in a single
      appointment. The initial concept comprised a small mobile CAD/CAM unit
      integrating a computer, keyboard, trackball, foot pedal and optoelectronic mouth
      camera as input devices, a monitor and a machining compartment. CEREC 3 (Sirona
      Dental Systems GmbH, Bensheim, Germany) divided the system into an
      acquisition/design unit and a separate machining unit. Three-dimensional software
      makes the handling illustrative and easy both in the office and in the
      laboratory. CONCLUSIONS: It appears that the CEREC CAD/CAM concept is becoming a
      significant part of dentistry. CLINICAL IMPLICATIONS: Sound knowledge of adhesive
      bonding and diligent planning are essential for the successful integration of
      CAD/CAM into clinical dental offices.

PMID- 16950933
TI  - Materials for chairside CAD/CAM-produced restorations.
AB  - BACKGROUND: and Overview. Although the use of computer-aided design/computer
      aided manufacturing (CAD/CAM) seems to be a recent addition to the dental
      restorative armamentarium, this concept was first investigated more than 35 years
      ago. CEREC (Sirona Dental Systems GmbH, Bensheim, Germany) was the first and is
      the only available chairside system, and it has more than 20 years of use in the
      dental office. The initial concept had three tenets: esthetic ceramic
      reconstruction, a single patient visit and minimal tooth reduction (inlays and
      onlays instead of crowns). The author reviews the materials used for CAD/CAM
      fabricated restorations. The structure, properties and clinical success of the
      materials for full-contour chairside restorations, as well as laboratory-based
      high-strength all-ceramic restorations are presented. RESULTS: CAD/CAM
      restorations have demonstrated clinical success owing to a combination of
      improvements in materials with advances in CAD/CAM systems. Full-contour ceramic
      restorations fabricated chair-side may reinforce the tooth, providing good long
      term clinical success. High-strength milled restorations allow for the use of all
      ceramic restorations for multiple-unit posterior and anterior bridges. CLINICAL
      IMPLICATIONS: Examination of the structure, properties and clinical results of
      CAD/CAM materials supports their use in routine dental practice.

PMID- 16950934
TI  - Clinical performance of chairside CAD/CAM restorations.
AB  - BACKGROUND: The CEREC system (Sirona Dental Systems GmbH, Bensheim, Germany) is
      marking its 20th year of clinical service. The author reviews the literature on
      the effectiveness of this chairside CAD/CAM system. TYPES OF STUDIES REVIEWED:
      The author identified and reviewed clinical studies from 1985 through 2006 that
      included CEREC-generated inlays, onlays or crowns. These studies were conducted
      in both private practice and university settings. The author summarized the
      findings as they relate to postoperative sensitivity, restoration fracture, color
      match, margin adaptation and clinical longevity. RESULTS: Although postoperative
      sensitivity was reported, it was due to mainly occlusal interferences. Long-term
      postoperative sensitivity was not a reported problem. Similar to other ceramic
      restorations, restoration fracture is the primary mode of failure for CEREC
      generated restorations. Although margin wear is detected consistently,
      consequences of the wear leading to restoration failure were reported rarely. The
      survival probability of CEREC-generated restorations was reported to be
      approximately 97 percent for five years and 90 percent for 10 years. CLINICAL
      IMPLICATIONS: The low rate of restoration fracture and long-term clinical
      survivability document the effectiveness of the CEREC system as a dependable,
      esthetic restorative option for patients.

PMID- 16950935
TI  - Making informed decisions about incorporating a CAD/CAM system into dental
      practice.
AB  - BACKGROUND: The authors drew from their clinical application and practice
      management experience to present a guide to incorporating into the dental
      practice computer-aided design/computer-aided manufacturing (CAD/CAM) technology
      for creating dental restorations. METHODS: The authors examine various factors in
      the purchase of CAD/CAM technology: clinical considerations and implications,
      practice and patient impact, and practical aspects of financial return. They also
      offer guidelines to and provide questions for dentists who may be considering a
      purchase of such technology. CONCLUSIONS: CAD/CAM technology is a key component
      for a technologically current dental office. CLINICAL IMPLICATIONS: Today's
      dental care consumer is more aware of his or her treatment options, and CAD/CAM
      technology may help the dentist meet such a patient's needs. With software
      improvement, attention to user-friendliness and positive clinical performance
      history, CAD/CAM systems are a significant stride forward into one-appointment
      esthetic dentistry.

PMID- 16950936
TI  - Potential of telemedicine in pediatric primary care.

PMID- 16950937
TI  - Systemic lupus erythematosus in children and adolescents.

PMID- 16950938
TI  - Altered states of consciousness.

PMID- 16950939
TI  - Child abuse and domestic violence.

PMID- 16950940
TI  - Consultation with the specialist: malaria prophylaxis in children.

PMID- 16950941
TI  - Index of suspicion.

PMID- 16950942
TI  - Colic.

PMID- 16950943
TI  - Morbidity and mortality of infants with very low birth weight in Japan: center
      variation.
AB  - OBJECTIVES: The objectives of this study were to describe the characteristics and
      morbidity of very low birth weight infants, to identify the medical intervention
      for these infants, and to evaluate the factors affecting the mortality of these
      infants among the participating hospitals. METHODS: A large multicenter neonatal
      research network that included level III NICUs from throughout Japan was
      established. A standardized mortality rate was formulated by giving a ratio of
      the observed deaths and the predicted deaths based on a 100-g birth weight
      interval mortality. A regression model was used to predict the factors that
      affect neonatal mortality. RESULTS: The network included 37 centers and 2145
      infants weighing < or = 1500 g, born or admitted to the centers in 2003.
      Gestational age and birth weight of studied infants were 28.6 +/- 3.6 gestational
      weeks (mean +/- SD) and 1025 +/- 302 g, respectively. Overall, 11% of the infants
      died before being discharged from hospitals (range: 0%-21%). The standardized
      mortality rate varied among the facilities (range: 0%-30%). No association
      between the annual number of patients admitted and standardized mortality rate
      was found. Among all of the very low birth weight infants, 14% were outborn
      infants, 72% were delivered by cesarean sections, 27% had patent ductus
      arteriosus, 3% had gastrointestinal perforation, 8% had bacterial sepsis, and 13%
      had intraventricular hemorrhage. Medical interventions involved were: 41%
      antenatal corticosteroids, 54% surfactant therapy, 18% postnatal steroids for
      chronic lung disease, and 29% high-frequency oscillatory ventilation. We found
      variations in the medical interventions and the clinical outcomes among the
      centers. CONCLUSIONS: The overall survival rate for very low birth weight infants
      among neonatal centers in Japan was approximately 90%. However, differences in
      the morbidity and mortality were observed among these centers.

PMID- 16950944
TI  - Pulmonary function assessment in an infant with Barnes syndrome: proactive
      evaluation for surgical intervention.
AB  - Our aim for this study was to report pulmonary mechanics in a neonate with a
      severe case of Barnes syndrome, a rare form of thoracolaryngopelvic dysplasia,
      and to use these data to guide ventilatory support and serve as a presurgical
      screening tool. A comprehensive pulmonary function evaluation was performed on a
      36-day-old patient with Barnes syndrome who was being mechanically ventilated
      because of severe pulmonary distress secondary to thoracic dystrophy. The
      measurements consisted of respiratory volumes including functional residual
      capacity, ventilatory mechanics including compliance and resistance, and
      thoracoabdominal synchrony. Chest wall compliance was 64% below normal, and the
      thoracoabdominal motion was indicative of predominantly abdominal displacement
      during inspiratory breaths. The lungs were functioning at a low functional
      residual capacity, resulting in low lung compliance and increased pulmonary
      resistance. As a result of the evaluation, the patient was recommended for
      lateral thoracic expansion surgery and the ventilatory management was adjusted to
      focus on end-distending pressure support.

PMID- 16950945
TI  - Serum lactate levels in infants exposed peripartum to antiretroviral agents to
      prevent mother-to-child transmission of HIV: Agence Nationale de Recherches Sur
      le SIDA et les Hepatites Virales 1209 study, Abidjan, Ivory Coast.
AB  - BACKGROUND: Mitochondrial toxicity was described in infants exposed to long-term
      antiretroviral regimens containing nucleoside analogues for the prevention of
      mother-to-child transmission of HIV. We measured the serum lactate levels in
      children born to HIV-1 infected African women receiving short-term antiretroviral
      prevention of mother-to-child transmission of HIV regimens. METHODS: A
      prospective study was conducted in women-child pairs from the third trimester of
      pregnancy to 3 months of life. The exposed group was formed by children exposed
      in utero to nucleoside analog antiretroviral regimens, zidovudine or zidovudine +
      lamivudine from 32 to 36 weeks of amenorrhea until delivery. All of these women
      received nevirapine single dose at the beginning of labor. The children received
      zidovudine during the first 7 days of life and a nevirapine single dose at day 3.
      The control group was formed by infants born to HIV-1-infected women who had
      received nevirapine single dose only and who were not exposed to nucleoside
      analog antiretroviral regimens. Serum lactate levels were measured at 4, 6, and
      12 weeks of life by Cobas Integra 400. RESULTS: A total of 836 blood samples from
      338 infants was collected (262 exposed and 76 controls). Median lactacidemia was
      1.8 mmol/L (interquartile range: 1.2-2.7 mmol/L). Overall serum lactate levels >
      or = 2.5 mmol/L, defining hyperlactatemia, were observed in 39 of the 292 infants
      who had > or = 2 serum lactate measurements. The 3-month period prevalence of
      hyperlactatemia did not differ between the exposed group and the control group.
      All of the serum lactate levels returned to normal values in all of the
      subsequent samples. No case of symptomatic hyperlactatemia was detected during
      the study period. CONCLUSIONS: Increased lactate levels were identified equally
      in infants whose mother received short-term nucleoside analogs or nevirapine
      single dose for prevention of mother-to-child transmission of HIV. Although not
      rare, hyperlactatemia was not related to short-term exposure to nucleoside analog
      antiretroviral regimens.

PMID- 16950946
TI  - Panayiotopoulos syndrome: a benign childhood autonomic epilepsy frequently
      imitating encephalitis, syncope, migraine, sleep disorder, or gastroenteritis.
AB  - BACKGROUND: Panayiotopoulos syndrome is a common idiopathic childhood-specific
      seizure disorder formally recognized by the International League Against
      Epilepsy. An expert consensus has defined Panayiotopoulos syndrome as "a benign
      age-related focal seizure disorder occurring in early and mid-childhood. It is
      characterized by seizures, often prolonged, with predominantly autonomic
      symptoms, and by an EEG [electroencephalogram] that shows shifting and/or
      multiple foci, often with occipital predominance." OBJECTIVE: The purpose of this
      review is to provide guidance for appropriate diagnosis and management of
      Panayiotopoulos syndrome. CLINICAL FEATURES: Autonomic epileptic seizures and
      autonomic status epilepticus are the cardinal manifestations of Panayiotopoulos
      syndrome. Autonomic seizures in Panayiotopoulos syndrome consist of episodes of
      disturbed autonomic function with emesis as the predominant symptom. Other
      autonomic manifestations include pallor (or, less often, flushing or cyanosis),
      mydriasis (or, less often, miosis), cardiorespiratory and thermoregulatory
      alterations, incontinence of urine and/or feces, hypersalivation, and
      modifications of intestinal motility. In approximately one fifth of the seizures
      the child becomes unresponsive and flaccid (ictal syncope) before or often
      without convulsions. Cardiorespiratory arrest is exceptional. More-conventional
      seizure symptoms often appear after the onset of autonomic manifestations. The
      child, who was initially fully conscious, becomes confused and unresponsive. Eyes
      turn to one side or gaze widely open. Only half of the seizures end with brief
      hemiconvulsions or generalized convulsions. Convulsive status epilepticus is
      extremely rare. Autonomic symptoms may be the only features of the seizures. Half
      of the seizures in Panayiotopoulos syndrome last for >30 minutes, thus
      constituting autonomic status epilepticus, which is the more common nonconvulsive
      status epilepticus in normal children. Two thirds of seizures occur during sleep.
      EPIDEMIOLOGY: Panayiotopoulos syndrome probably affects 13% of children aged 3 to
      6 years who have had 1 or more afebrile seizures and 6% of such children in the 1
      to 15-year age group. DIAGNOSTIC TESTS: An electroencephalogram is the only
      investigation with abnormal results, usually showing multiple spikes in various
      brain locations. PATHOPHYSIOLOGY: Panayiotopoulos syndrome is probably the early
      onset and Rolandic epilepsy the late-onset phenotype of a maturation-related
      benign childhood seizure-susceptibility syndrome. Ictal epileptic discharges in
      Panayiotopoulos syndrome, irrespective of their location at onset, activate
      autonomic disturbances and emesis, to which children are particularly vulnerable.
      The symptoms/sequence of autonomic seizures and autonomic status epilepticus in
      Panayiotopoulos syndrome are specific to childhood, and they do not occur in
      adults. PROGNOSIS: Panayiotopoulos syndrome is remarkably benign in terms of
      seizure frequency and evolution. Autonomic status epilepticus imparts no residual
      neurologic deficit. The risk of epilepsy in adult life seems to be no higher than
      in the general population. However, autonomic seizures are potentially life
      threatening in the rare context of cardiorespiratory arrest, an area in which
      additional study is required. MISDIAGNOSIS: The clinical features of
      Panayiotopoulos syndrome are frequently mistaken as nonepileptic conditions such
      as acute encephalitis, syncope, migraine, cyclic vomiting syndrome, motion
      sickness, sleep disorder, or gastroenteritis. The consequence is avoidable
      misdiagnosis, high morbidity, and costly mismanagement. MANAGEMENT: Education
      about Panayiotopoulos syndrome is the cornerstone of management. Prophylactic
      treatment with antiepileptic medication may not be needed for most patients.
      Autonomic status epilepticus in the acute stage needs thorough evaluation;
      aggressive treatment may cause iatrogenic complications including
      cardiorespiratory arrest.

PMID- 16950947
TI  - Diagnosis and management of food-induced anaphylaxis: a national survey of
      pediatricians.
AB  - BACKGROUND: Food allergy is a common pediatric problem, affecting as many as 6%
      of young children, yet it is unclear whether pediatricians are well prepared to
      manage food-induced anaphylaxis. OBJECTIVE: The purpose of this work was to
      assess pediatricians' knowledge of diagnosis and management of children with food
      induced anaphylaxis. METHODS: A survey designed to assess food allergy diagnosis
      and management was mailed to a US national random sample of 1130 pediatricians.
      Survey questions were based on a clinical scenario involving a child having an
      anaphylactic reaction after ingesting peanut. Primary outcome measures included
      correct responses to the 11 questions about anaphylaxis. RESULTS: A total of 468
      pediatricians (41%) responded to the survey. The majority of the respondents were
      women (58%), spent > 50% of their time in a clinical setting (78%), and reported
      providing care for food allergy patients (86%). Overall, 70% of the pediatricians
      agreed that the clinical scenario was consistent with anaphylaxis, and 72% chose
      to administer epinephrine. However, only 56% of respondents agreed with both the
      diagnosis of anaphylaxis and treating with epinephrine. Most pediatricians (70%)
      did not recognize that a 30-minute observation period after anaphylaxis was too
      short. Pediatricians who reported providing care for food allergy patients were
      more likely to agree with the diagnosis of anaphylaxis (73% vs 59%), with
      treating the reaction with epinephrine (73% vs 64%), and with prescribing self
      injectable epinephrine (83% vs 66%) than pediatricians who did not care for food
      allergy patients. The more certain that pediatricians were that the child was
      having an anaphylactic reaction, the more likely they were to agree with treating
      the reaction with epinephrine. In general, recent continuing medical education
      was not predictive of improved knowledge. CONCLUSION: Although the majority of
      pediatricians seem to have some knowledge of food-induced anaphylaxis, a
      substantial proportion has knowledge deficits that may hinder their ability to
      provide optimal care to children with food-induced anaphylaxis. Pediatricians who
      provide health care for patients with food allergy may be better equipped to
      manage food-induced anaphylaxis than those who do not. Because continuing medical
      education was not a significant predictor of increased knowledge, ensuring that
      pediatric residents develop experience managing patients with food allergies may
      be a better strategy to educate primary care pediatricians about food allergy.

PMID- 16950948
TI  - Influenza vaccine immunogenicity in 6- to 23-month-old children: are identical
      antigens necessary for priming?
AB  - OBJECTIVES: Immunoprophylaxis with influenza vaccine is the primary method for
      reducing the effect of influenza on children, and inactivated influenza vaccine
      has been shown to be safe and effective in children. The Advisory Committee on
      Immunization Practices recommends that children 6 to 23 months of age who are
      receiving trivalent inactivated influenza vaccine for the first time be given 2
      doses; however, delivering 2 doses of trivalent inactivated influenza vaccine >
      or = 4 weeks apart each fall can be logistically challenging. We evaluated an
      alternate spring dosing schedule to assess whether a spring dose of trivalent
      inactivated influenza vaccine was capable of "priming" the immune response to a
      fall dose of trivalent inactivated influenza vaccine containing 2 different
      antigens. PATIENTS AND METHODS: Healthy children born between November 1, 2002,
      and December 31, 2003, were recruited in the spring and randomly assigned to
      either the alternate spring schedule or standard fall schedule. The 2003-2004
      licensed trivalent inactivated influenza vaccine was administered in the spring;
      the fall 2004-2005 vaccine had the same A/H1N1 antigen but contained drifted
      A/H3N2 antigen and B antigen with a major change in strain lineage.
      Reactogenicity was assessed by parental diaries and telephone surveillance. Blood
      was obtained after the second dose of trivalent inactivated influenza vaccine for
      all of the children and after the first dose of trivalent inactivated influenza
      vaccine in the fall group. The primary outcome of this study was to demonstrate
      noninferiority of the antibody response after a spring-fall dosing schedule
      compared with the standard fall dosing schedule. Noninferiority was based on the
      proportion of subjects in each group achieving a hemagglutination-inhibition
      antibody titer of > or = 1:32 after vaccination to 2 of the 3 antigens (H1N2,
      H3N2, and B) contained in the 2004-2005 vaccine. For each antigen, the antibody
      response was proposed to be noninferior if, within the upper bound of 95%
      confidence interval, there was < 15% difference between the proportion of
      children in the fall and spring groups with postvaccination titers > or = 1:32.
      RESULTS: A total of 468 children were randomly assigned to either the spring (n =
      233) or fall (n = 235) trivalent inactivated influenza vaccine schedule.
      Excellent response rates to A/H1N1, as measured by antibody levels > or = 1:32,
      were noted in both the spring (86%) and fall groups (93%). The A/H1N1 response
      rate of the spring group was noninferior to that of the fall group.
      Noninferiority of the spring schedule was not met with respect to the other 2
      influenza antigens: for A/H3N2 the response was 70% in the spring group versus
      83% for the fall group, and the response to B was 39% in the spring group versus
      88% for the fall group. After 2 doses of vaccine, the geometric mean antibody
      titers also were less robust in the spring group for both A/H3N2 and B antigens.
      For each of the 3 vaccine antigens, the respective geometric mean antibody titers
      for the spring group versus the fall group were: A/H1N1, 79.5 +/- 3.3 and 91.9 +/
      2.6; A/H3N2, 57.1 +/- 4.1 and 77.8 +/- 3.7; and B, 18.0 +/- 2.4 and 61.6 +/-
      2.5. However, a significantly higher proportion of children in the spring group
      achieved potentially protective levels of antibody to all 3 antigens after their
      first fall dose of trivalent inactivated influenza vaccine than children in the
      fall group after receiving their first fall dose. For influenza A/H1N1, there was
      an antibody level > or = 1:32 in 86% of children in the spring group versus 55%
      of children in the fall group. Likewise, for influenza A/H3N2, 70% of children in
      the spring group and 47% of children in the fall group had antibody levels >
      1:32; for influenza B, the proportions were 39% of children in the spring group
      and 16% of children in the fall group. Reactogenicity after trivalent inactivated
      influenza vaccine in both groups of children was minimal and did not differ by
      dose. CONCLUSIONS: Although the immune response to the identical A/H1N1 vaccine
      antigen was similar in both groups, priming with different A/H3N2 antigens and B
      antigens in the spring produced a lower immune response to both antigens than
      that shown in children who received 2 doses of the same vaccine in the fall.
      However, approximately 70% of children in the spring group had a protective
      response to the H3N2 antigen after 2 doses. Initiating influenza immunization in
      the spring was superior to 1 dose of trivalent inactivated influenza vaccine in
      the fall. The goal of delivering 2 doses of influenza vaccine a month apart to
      vaccine-naive children within the narrow flu vaccination season is a challenge
      not yet met; thus far, only about half of children aged 6 to 23 months of age are
      receiving influenza vaccine. By using the spring schedule, we were able to
      administer 2 doses of trivalent inactivated influenza vaccine to a higher
      proportion of children earlier in the influenza vaccination season. In years when
      there is an ample supply of trivalent inactivated influenza vaccine, and vaccine
      remains at the end of the season, priming influenza vaccine-naive infants with a
      spring dose will lead to the earlier protection of a higher proportion of infants
      in the fall. This strategy may be particularly advantageous when there is an
      early start to an influenza season as occurred in the fall of 2003. A priming
      dose of influenza vaccine in the spring may also offer other advantages. Many
      vaccine-naive children may miss the second dose of fall trivalent inactivated
      influenza vaccine because of vaccine shortages or for other reasons, such as the
      potential implementation of new antigens at a late date. Even with seasonal
      changes in influenza vaccine antigens, by giving a springtime dose of trivalent
      inactivated influenza vaccine, such children would be more protected against
      influenza than would children who were only able to receive 1 dose in the fall.
      In summary, our data suggest that identical influenza antigens are not necessary
      for priming vaccine-naive children and that innovative uses of influenza vaccine,
      such as a springtime dose of vaccine, could assist in earlier and more complete
      immunization of young children.

PMID- 16950949
TI  - Immunization with trivalent inactivated influenza vaccine in partially immunized
      toddlers.
AB  - OBJECTIVE: Children > or = 6 months of age who have previously received 1 dose of
      trivalent inactivated influenza vaccine are recommended to be given an additional
      single trivalent inactivated influenza vaccine dose the following fall. Limited
      data exist documenting the immunogenicity of 2 doses of influenza vaccine given
      in separate years to young children, and it is not known if the antigen content
      of each of the 2 doses of vaccine must be identical or similar to optimally
      immunize children in this age group. In 2004, the A/H3N2 and B antigens contained
      in trivalent inactivated influenza vaccine were changed from those in the 2003
      2004 influenza vaccine, providing the opportunity to assess the effect of such a
      change on the single-dose recommendation in trivalent inactivated influenza
      vaccine-experienced toddlers. PATIENTS AND METHODS: We conducted an
      observational, nonrandomized, open-label study comparing immunogenicity and
      reactogenicity of 2 doses of trivalent inactivated influenza vaccine in 2 groups
      of healthy children aged 6 to 23 months. Children who had received 1 dose of 2003
      trivalent inactivated influenza vaccine the previous season received 1 dose of
      2004 trivalent inactivated influenza vaccine according to current guidelines
      (group 1). Trivalent inactivated influenza vaccine-naive toddlers received the
      standard 2 doses of 2004 trivalent inactivated influenza vaccine 1 month apart
      (group 2). Blood was obtained 4 weeks after the second dose of trivalent
      inactivated influenza vaccine. The primary outcome measure was antibody response
      to the 3 vaccine antigens in the 2004 trivalent inactivated influenza vaccine
      after 2 doses of vaccine, as determined by hemagglutination-inhibition antibody
      titers. Noninferiority of the antibody response was based on the proportion of
      subjects in each group achieving a titer of > or = 1:32 postvaccination to
      antigens (H1N1, H3N2, and B) contained in the 2004-2005 vaccine. For each
      antigen, the antibody response was proposed to be noninferior if the upper bound
      of the 95% confidence interval of the difference between the proportion of
      children in the 2 groups with postvaccination titers > or = 1:32 was < 15%.
      Reactogenicity was a secondary outcome and was assessed by parental diaries or
      telephone follow-up. RESULTS: Fifty six of 58 previously immunized children
      (group 1) and 63 of 64 vaccine-naive children (group 2) completed the study. The
      groups were similar, except group 1 was older at receipt of the second trivalent
      inactivated influenza vaccine. Reactogenicity did not differ by age or time
      between doses. Antibody responses to the unchanged influenza A/H1N1 antigen at 4
      weeks after the second trivalent inactivated influenza vaccine dose were similar
      in both groups, with good responses as measured by geometric mean titer (75.2 vs
      69.1) and percentage with antibody titers > or =1:32 (82.1% group 1 vs 85.7%
      group 2). For the A/H3N2 antigen, which changed between 2003 and 2004, there was
      a significantly higher geometric mean titer in group 1 compared with group 2 (156
      vs 53.7), but both groups had very high rates of seroconversion that were not
      statistically different (91% vs 84%). The antibody response to influenza B was
      significantly lower in group 1 recipients, who received only a single dose of
      2005 vaccine, as measured by both geometric mean titer and percentage with
      antibody > or = 1:32. The group 1 geometric mean titer was 13.8, and the group 2
      geometric mean titer was 49.1. Only 27% of children in group 1 achieved antibody
      levels > or = 1:32 to influenza B compared with 86% in group 2. Using logistic
      regression, we also determined that older children had less potentially
      seroprotective levels to influenza B. Overall, noninferiority of the antibody
      response for group 1 compared with group 2 was confirmed for influenza A/H3N2,
      was marginally significant for A/H1N1, and was not confirmed for influenza B.
      CONCLUSIONS: The assessment of immune responses in children after changes in
      vaccine composition is important, because influenza vaccines change frequently,
      affecting not only antibody responses in partially immunized toddlers, but
      potentially immune responses in more fully immunized individuals. In this study,
      a change in 2 different vaccine antigens enabled us to assess and compare the
      impact of the original priming antigens after relatively minor changes in 1
      antigen (A/H3N2) or after considerable antigenic changes in another vaccine
      antigen (B). Our subjects demonstrated relatively good responses to the vaccine
      antigen change characterized by relatively minor changes (A/H3N2). Circulating
      virus may have primed infants in both groups to antigen more closely related to
      the 2004 influenza A/H3N2 strain. The high A/H3N2 antibody response to the second
      dose of trivalent inactivated influenza vaccine in children who were immunized
      the previous fall with a different vaccine is consistent with the fact that more
      children in group 1 were alive during this epidemic and, therefore, were more
      likely to have experienced priming with natural infection. In contrast, a
      decreased antibody response to the influenza B antigen was seen in children
      primed with the earlier 2003 vaccine, suggesting that the major change in B virus
      lineage in the 2004 vaccine reduced the priming benefit of previous vaccination.
      Our findings are reminiscent of antibody responses in children seen after
      immunization with different but novel influenza antigens, such as swine flu
      vaccine (influenza A/swine/1976/37-like virus). Our results should be taken into
      account when evaluating new vaccines in young children for novel viruses, such as
      new pandemic strains of influenza. The need for multiple doses of vaccine to
      produce potentially protective antibody levels in children needs to be
      considered, even when vaccine is in short supply.

PMID- 16950950
TI  - Sustained effects of cardiac rehabilitation in children with serious congenital
      heart disease.
AB  - OBJECTIVE: Past studies have documented the acute benefits of cardiac
      rehabilitation in children with congenital heart disease. It is not known whether
      these benefits persist. PATIENTS AND METHODS: Fifteen patients, ages 8 to 17
      years, with complex congenital heart disease, whose exercise function immediately
      after a 12-week cardiac rehabilitation program was superior to that present on a
      precardiac rehabilitation exercise test, were restudied 6.9 +/- 1.6 months after
      completion of the cardiac rehabilitation program (approximately 1 year after the
      precardiac rehabilitation study). Changes in exercise function relative to
      baseline, precardiac rehabilitation exercise tests were also compared with
      changes observed in a group of 18 control subjects, with similar diagnoses, who
      also had 2 exercise tests separated by a year but did not undergo cardiac
      rehabilitation. RESULTS: The cardiac rehabilitation patients' exercise function
      did not change significantly over the 6.9-month period after the completion of
      the cardiac rehabilitation program; percentage of predicted peak oxygen
      consumption and peak work rate remained significantly superior to baseline,
      precardiac rehabilitation values. These changes were also associated with
      improvements in self-esteem, behavior, and emotional state. In contrast, among
      the control subjects, small, but statistically insignificant declines in peak
      oxygen consumption and peak work rate were observed on the final exercise test
      compared with values obtained at baseline, 1 year earlier. The improvements
      realized by the cardiac rehabilitation patients differed significantly from the
      concurrent changes observed among the control subjects and appeared to be a
      result of an increase in the oxygen pulse at peak exercise; significant changes
      in peak heart rate were not observed. CONCLUSIONS: In patients with congenital
      heart disease, cardiac rehabilitation produces significant, sustained
      improvements in exercise function, behavior, self-esteem, and emotional state.

PMID- 16950951
TI  - Identifying risk for obesity in early childhood.
AB  - OBJECTIVES: Our aim with this study was to assist clinicians by estimating the
      predictive value of earlier levels of BMI status on later risk of overweight and
      obesity during the middle childhood and early adolescent years. METHODS: We
      present growth data from the National Institute of Child Health and Human
      Development Study of Early Child Care and Youth Development, a longitudinal
      sample of 1042 healthy US children in 10 locations. Born in 1991, their growth
      reflects the secular trend of increasing overweight/obesity in the population.
      Height and weight of participating children in the study were measured at 7 time
      points. We examined odds ratios for overweight and obesity at age 12 years
      comparing the frequency with which children did versus did not reach specific BMI
      percentiles in the preschool- and elementary-age periods. To explore the question
      of whether and when earlier BMI was predictive of weight status at age 12 years,
      we used logistic regression to obtain the predicted probabilities of being
      overweight or obese (BMI > or = 85%) at 12 years old on the basis of earlier BMI.
      RESULTS: Persistence of obesity is apparent for both the preschool and elementary
      school period. Children who were ever overweight (> 85th percentile), that is, >
      or = 1 time at ages 24, 36, or 54 months during the preschool period were > 5
      times as likely to be overweight at age 12 years than those who were below the
      85th percentile for BMI at all 3 of the preschool ages. During the elementary
      school period, ages 7, 9, and 11 years, the more times a child was overweight,
      the greater the odds of being overweight at age 12 years relative to a child who
      was never overweight. Sixty percent of children who were overweight at any time
      during the preschool period and 80% of children who were overweight at any time
      during the elementary period were overweight at age 12 years. Follow-up
      calculations showed that 2 in 5 children whose BMIs were > or = 50th percentile
      by age 3 years were overweight at age 12 years. No children who were < 50th
      percentile for BMI at all points during elementary school were overweight at age
      12 years. Children who have higher range BMIs earlier, but not at the 85th
      percentile, are also more likely to be overweight at age 12 years. Even at time
      points before and including age 9 years, children whose BMIs are between the 75th
      and 85th percentile have an approximately 40% to 50% chance of being overweight
      at age 12 years. Children at 54 months old whose BMIs are between the 50th and
      75th percentile are 4 times more likely to be overweight at age 12 years than
      their contemporaries who are < 50th percentile, and those whose BMIs are between
      the 75th and 85th percentile are > 6 times more likely to be overweight at age 12
      years than those < 50th percentile. CONCLUSIONS: The data from this study
      indicate that children with BMIs > 85th percentile, as well as with BMIs in the
      high reference range are more likely than children whose BMI is < 50th percentile
      to continue to gain weight and reach overweight status by adolescence.
      Pediatricians can be confident in counseling parents to begin to address the at
      risk child's eating and activity patterns rather than delaying in hopes that
      overweight and the patterns that support it will resolve themselves in due
      course. Identifying children at risk for adolescent obesity provides physicians
      with an opportunity for earlier intervention with the goal of limiting the
      progression of abnormal weight gain that results in the development of obesity
      related morbidity.

PMID- 16950952
TI  - Immunogenicity and safety of an inactivated hepatitis A vaccine administered
      concomitantly with diphtheria-tetanus-acellular pertussis and haemophilus
      influenzae type B vaccines to children less than 2 years of age.
AB  - OBJECTIVE: The availability of a hepatitis A virus vaccine for infant and early
      childhood immunization could reduce the transmission of hepatitis A virus in the
      United States. This study evaluated the immunogenicity and safety of a hepatitis
      A virus vaccine (Havrix, GlaxoSmithKline Biologicals, Rixensart, Belgium)
      administered concomitantly with diphtheria-tetanus-acellular pertussis and
      Haemophilus influenzae type b vaccines to children < 2 years. METHODS: In this
      open, comparative, multicenter study, 1084 healthy children aged 11 to 25 months
      were allocated (4:4:3:3:4 ratio) to 5 treatment groups based on age and previous
      vaccination history. Subjects 11 to 13 months of age received 2 doses of
      hepatitis A virus vaccine 6 months apart (N = 243). Subjects aged 15 to 18 months
      received 2 doses of hepatitis A virus vaccine 6 months apart (N = 241); or
      hepatitis A virus vaccine, diphtheria-tetanus-acellular pertussis, and H
      influenzae type b at month 0 and the second dose of hepatitis A virus vaccine 6
      months later (N = 183); or diphtheria-tetanus-acellular pertussis and H
      influenzae type b at month 0 and hepatitis A virus vaccine at months 1 and 7 (N =
      175). Subjects 23 to 25 months of age received hepatitis A virus vaccine at
      months 0 and 6 (N = 242). Immune responses were measured at baseline and 30 days
      after vaccine doses, and solicited and unsolicited adverse events were collected.
      RESULTS: After 2 doses of hepatitis A virus vaccine, all of the subjects in all
      of the groups were seropositive. Coadministration of hepatitis A virus vaccine
      with diphtheria-tetanus-acellular pertussis and H influenzae type b vaccines did
      not impact the immunogenicity of the 3 vaccines, except for the antipertussis
      toxoid vaccine response, which was slightly decreased. Hepatitis A virus vaccine
      was well tolerated in children 11 to 25 months of age. CONCLUSION: The
      administration of 2 doses of hepatitis A virus vaccine on a 0- and 6-month
      schedule starting at 11 to 13 months of age or at 15 to 18 months of age was as
      immunogenic and well tolerated as the administration of 2 doses in children 2
      years of age. Immune responses to diphtheria-tetanus-acellular pertussis and H
      influenzae type b either given alone or coadministered with hepatitis A virus
      vaccine were similar except for antipertussis toxoid response.

PMID- 16950953
TI  - Surveillance for influenza admissions among children hospitalized in Canadian
      immunization monitoring program active centers, 2003-2004.
AB  - OBJECTIVES: Influenza is a common childhood infection that may result in
      hospitalization. Our objectives were to (1) determine characteristics of children
      hospitalized for influenza and disease manifestations and (2) obtain baseline
      data before implementation of new recommendations for routine immunization of
      young children and their caretakers against influenza. METHODS: All of the
      children hospitalized with laboratory-confirmed influenza at 9 Canadian tertiary
      care hospitals during the 2003-2004 influenza season were identified from
      virology laboratory reports, and their charts were reviewed. RESULTS: There were
      505 children admitted because of influenza. Fifty-seven percent were < 2 years
      old. Previously healthy children accounted for 58% of all of the cases. Pulmonary
      and neurologic disorders were the most common underlying chronic conditions.
      Fever and cough were the most frequent manifestations. Seizures occurred in 9% of
      cases. Serious complications included myocarditis (2), encephalopathy (6), and
      meningitis (1). There were 3 influenza-related deaths. Mean duration of
      hospitalization was 5.3 days. Twelve percent of children required ICU admission,
      and 6% required mechanical ventilation. Antibiotic therapy was administered in
      77% of cases, and 7% received anti-influenza drugs. Information on influenza
      vaccination was available for 84 of 154 children identified as vaccine
      candidates. Twenty two had received vaccine, but only 7 children had been fully
      immunized > 14 days before the onset of illness. CONCLUSIONS: Healthy young
      children and children with chronic conditions are at risk for serious illness
      with influenza. Ongoing surveillance is needed to evaluate the impact of changing
      immunization recommendations on the burden of influenza illness in children.

PMID- 16950954
TI  - A national survey of terrorism preparedness training among pediatric, family
      practice, and emergency medicine programs.
AB  - OBJECTIVES: Domestic terrorism is a real threat focusing on a need to engage in
      effective emergency preparedness planning and training. Front-line physicians are
      an important component of any emergency preparedness plan. Potential victims of
      an attack include children who have unique physiologic and psychological
      vulnerabilities in disasters. Front-line providers need to have adequate training
      to effectively participate in local planning initiatives and to recognize and
      treat casualties including children. The goal of the survey was to assess the
      current state of terrorism preparedness training, including child victims, by
      emergency medicine, family practice, and pediatric residency programs in the
      United States and to assess methods of training and barriers to establishing
      effective training. METHODS: A survey was e-mailed to a comprehensive list of all
      US pediatric, family practice, and emergency medicine residency programs 3 times
      between September 2003 and January 2004. The survey measured the perceived risk
      of terrorist attack, level of training by type of attack, level of training
      regarding children, method of training, and barriers to training. RESULTS:
      Overall, 21% of programs responded (46 of 182 pediatric, 75 of 400 family
      practice, and 29 of 125 emergency medicine programs). Across all of the event
      types, emergency medicine programs were more likely to report
      adequate/comprehensive training. However, < 50% of emergency medicine programs
      report adequate training for children. Didactic classroom-based lectures were the
      most commonly used method of training. Emergency medicine programs were more
      likely to use scenario-based exercises. Among programs that use scenario
      exercises, 93% report that they never (40%) or only sometimes (53%) incorporate
      child victims into the scenarios. Time, funding, access to subject matter
      experts, and availability of training material are the most important barriers to
      effective training. CONCLUSIONS: Children are a precious national resource and a
      vulnerable population in disasters. Despite the availability of terrorism
      preparedness funding, these data suggest that we are failing to provide adequate
      training to front-line providers who may care for children in a catastrophic
      domestic terrorist event.

PMID- 16950955
TI  - A controlled, randomized, double-blind trial to evaluate the effect of a
      supplement of cocoa husk that is rich in dietary fiber on colonic transit in
      constipated pediatric patients.
AB  - OBJECTIVE: Although a diet that is rich in fiber is widely recommended for
      preventing and treating constipation, the efficacy of fiber supplements have not
      been tested sufficiently in children. Our aim with this pilot study was to
      evaluate if fiber supplementation is beneficial for the treatment of children
      with idiopathic chronic constipation. METHODS: Using a parallel, randomized,
      double-blind, controlled trial, we conducted an interventional study to evaluate
      the efficacy of a supplement of cocoa husk rich in dietary fiber on intestinal
      transit time and other indices of constipation in children with constipation.
      After screening, the patients were randomly allocated to receive, for a period of
      4 weeks, either a cocoa husk supplement or placebo plus standardized toilet
      training procedures. Before and after 4 weeks of treatment, we (1) performed
      anthropometry, a physical examination, and routine laboratory measurements, (2)
      determined total and segmental colonic transit time, (3) evaluated bowel movement
      habits and stool consistency using a diary, and (4) received a subjective
      evaluation from the parents regarding the efficacy of the treatment. The main
      variable for verifying the efficacy of the treatment was the total colonic
      transit time. RESULTS: Fifty-six chronically constipated children were randomly
      assigned into the study, but only 48 children completed it. These children, who
      were aged between 3 and 10 years, had a diagnosis of chronic idiopathic
      constipation. With respect to total, partial colon, and rectum transit time,
      there seemed to be a trend, although statistically nonsignificant, toward faster
      transit times in the cocoa husk group than in the placebo group. When we analyzed
      the evolution of the intestinal transit time throughout the study of children
      whose total basal intestinal transit time was > 50th percentile, significant
      differences were observed between the groups. The total transit time decreased by
      45.4 +/- 38.4 hours in the cocoa husk group and by 8.7 +/- 28.9 hours in the
      placebo group (-38.1 hours). In the case of the right colon, changes in transit
      time also were significant between groups. Mean changes tended toward faster
      transit times in the left colon and the rectum, although the differences were not
      statistically significant. The children who received cocoa husk supplements
      tended to increase the number of bowel movements by more than that of the
      children of the placebo group. We also observed a reduction in the percentage of
      patients who reported hard stools (hard scybalous or pebble-like stools),
      although this reduction was significantly greater in the cocoa husk group. At the
      end of the intervention, 41.7% and 75.0% of the patients who received cocoa husk
      supplementation or placebo, respectively, reported having hard stools. Moreover,
      a significantly higher number of children (or their parents) reported a
      subjective improvement in stool consistency. No significant adverse effects were
      reported during the study. CONCLUSIONS: This study confirms the beneficial effect
      of a supplement of cocoa husk that is rich in dietary fiber on chronic idiopathic
      constipation in children. These benefits seem to be more evident in pediatric
      constipated patients with slow colonic transit time.

PMID- 16950956
TI  - Changing their minds with time: a comparison of hypothetical and actual
      reproductive behaviors in parents of children with cystic fibrosis.
AB  - OBJECTIVE: Newborn screening for cystic fibrosis, with appropriate counseling,
      enables carrier parents to be informed early about future reproductive choices.
      Previous studies have assessed attitudes toward reproductive decisions in a
      hypothetical pregnancy or have measured reproductive behaviors. We aimed to
      measure parent attitudes to reproductive technologies and to compare
      prospectively these attitudes with later reproductive behaviors. METHODS: Parents
      of children who had cystic fibrosis and were aged 2 to 7 years were surveyed at
      baseline using a written questionnaire that explored attitudes to prenatal
      testing and termination of pregnancy in a hypothetical pregnancy. Parent
      knowledge and access to genetic counseling services also were assessed. Five
      years later, we compared attitudes with actual reproductive behaviors. RESULTS:
      Fifty-six mothers participated at baseline, and 43 were resurveyed 5 years later.
      Parent knowledge of cystic fibrosis and genetics was very good. A total of 93%
      had met a genetic counselor at the time of diagnosis, and more than half had on
      at least 1 subsequent occasion. At baseline, 82% reported that they would be
      likely to have prenatal diagnosis in a subsequent pregnancy, and 56% reported
      that they would be likely to terminate an affected pregnancy. Twenty-seven
      mothers since had been pregnant, with prenatal diagnosis used in 33 of the 55
      pregnancies. In 67%, the hypothetically reported behavior regarding use of
      prenatal testing was the same as their actual behavior. Five of the 33 tested
      pregnancies were affected; all ended in termination. Reproductive choices in
      relationship to the number of children wanted, together with attitudes toward
      prenatal diagnosis and termination of pregnancy, were dynamic over time, with
      decisions having changed in both directions. CONCLUSIONS: This cohort of parents
      has actively used reproductive technologies since the birth of a child who has
      cystic fibrosis that was diagnosed by newborn screening. The dynamic aspect of
      reproductive choices highlights the importance of ongoing access to genetic
      counseling beyond the initial period of diagnosis and education, regardless of
      whether parents report that they expect to use reproductive technologies.

PMID- 16950957
TI  - Pediatricians' knowledge, training, and experience in the care of children with
      fetal alcohol syndrome.
AB  - OBJECTIVES: Prenatal exposure to alcohol interferes with fetal development and is
      the leading preventable cause of birth defects and developmental disabilities.
      The purpose of this study was to identify current knowledge, diagnosis,
      prevention, and intervention practices related to fetal alcohol syndrome and
      related conditions by members of the American Academy of Pediatrics. METHODS:
      This study was developed collaboratively by the American Academy of Pediatrics
      and the Centers for Disease Control and Prevention. Questionnaires were mailed to
      a 3% random sample (n = 1600) of American Academy of Pediatrics members in the
      United States. General pediatricians, pediatric subspecialists, and pediatric
      residents were included. RESULTS: Participation rate was 55% (n = 879).
      Respondents almost universally knew the teratology and clinical presentation of
      fetal alcohol spectrum disorders. However, they were less likely to report
      comfort with routine pediatric care of these children. Whereas 62% felt prepared
      to identify and 50% felt prepared to diagnose, only 34% felt prepared to manage
      and coordinate the treatment of children with fetal alcohol spectrum disorders.
      Even fewer (n = 114 [13%]) reported that they routinely counsel adolescent
      patients about the risks of drinking and pregnancy. CONCLUSIONS: The survey
      confirms that pediatricians are knowledgeable about fetal alcohol syndrome but do
      not feel adequately trained to integrate the management of this diagnosis or
      prevention efforts into everyday practice. Furthermore, the respondents were not
      active in routine anticipatory guidance with adolescents for prevention of
      alcohol-affected pregnancies. The development, dissemination, and implementation
      of best practice tools for prevention, diagnosis, and referral of fetal alcohol
      syndrome that are specific for general and subspecialist pediatricians are
      recommended.

PMID- 16950958
TI  - Adverse perinatal outcomes and risk for postpartum suicide attempt in Washington
      state, 1987-2001.
AB  - OBJECTIVE: Postpartum suicide attempts are serious events with a significant
      impact on women and their families. Our objectives were to determine the temporal
      risk period for these events and to assess whether maternal complications and
      adverse infant outcomes are associated with risk for postpartum suicide attempt.
      METHODS: We performed a case-control study that compared 520 women who were
      hospitalized for a postpartum suicide attempt with 2204 control women who were
      not hospitalized for a postpartum suicide attempt in Washington State from 1987
      to 2001. We performed logistic regression to evaluate whether maternal
      complications and adverse infant outcome, after controlling for other risk
      factors, were associated with a hospitalization for a suicide attempt within 1
      year after delivery. RESULTS: Most attempts were the result of poisoning (63.6%).
      Suicide attempts were most frequent in the first and 12th months after delivery.
      Maternal complications including labor and delivery complications and cesarean
      delivery were not associated with risk for postpartum suicide attempt. After
      adjustment for age and marital status, fetal or infant death was associated with
      postpartum suicide attempt. Other adverse infant outcomes, including preterm
      delivery, low birth weight, and congenital malformations, were not associated
      with attempts. CONCLUSIONS: Maternal complications were not associated with
      hospitalizations for suicide attempts in the year after delivery. However, fetal
      death or the death of an infant in the first year after delivery was strongly
      associated with hospitalization for a suicide attempt. These risk factors may be
      useful predictors for health care providers who care for women or children during
      the postpartum period.

PMID- 16950959
TI  - Detection of acetaminophen protein adducts in children with acute liver failure
      of indeterminate cause.
AB  - OBJECTIVE: Acetaminophen cysteine protein adducts are a widely recognized
      correlate of acetaminophen-mediated hepatic injury in laboratory animals. The
      objective of this study was to use a new assay for the detection of acetaminophen
      cysteine protein adducts in children with acute liver failure to determine the
      role of acetaminophen toxicity in acute liver failure of unknown cause. METHODS:
      Serum samples from children with acute liver failure were measured for
      acetaminophen cysteine protein adducts using high-performance liquid
      chromatography with electrochemical detection. For comparison, samples from
      children with well-characterized acetaminophen toxicity and children with known
      other causes of acute liver failure also were measured for acetaminophen cysteine
      protein adducts. The analytical laboratory was blinded to patient diagnoses.
      RESULTS: Acetaminophen cysteine protein adduct was detected in 90% of samples
      from children with acute liver failure that was attributed to acetaminophen
      toxicity, 12.5% of samples from children with acute liver failure of
      indeterminate cause, and 9.6% of samples from children with acute liver failure
      that was attributed to other causes. Adduct-positive patients from the
      indeterminate cause subgroup had higher levels of serum aspartate
      aminotransferase and alanine aminotransferase and lower levels of bilirubin.
      Adduct-positive patients also had lower rates of transplantation and higher rates
      of spontaneous remission. CONCLUSIONS: A small but significant percentage of
      children with acute liver failure of indeterminate cause tested positive for
      acetaminophen cysteine protein adducts, strongly suggesting acetaminophen
      toxicity as the cause of acute liver failure. An assay for the detection of
      acetaminophen cysteine protein adducts can aid the diagnosis of acetaminophen
      related liver injury in children.

PMID- 16950960
TI  - Breastfeeding and developmental delay: findings from the millennium cohort study.
AB  - OBJECTIVE: We investigated whether the duration and exclusivity of breastfeeding
      affects the likelihood of gross and fine motor delay in infants and examined the
      effect of factors that might explain any observed differences. METHODS: The study
      sample included all term singleton infants who weighed > 2500 g at birth and were
      not placed in a special care infant unit and whose mothers participated in the
      first survey of the Millennium Cohort Study. Missing data reduced the sample to
      14660 (94%) with complete data. RESULTS: Almost half (47%) of the infants
      initially were exclusively breastfed, but only 3.5% of these infants were still
      being fed exclusively on breast milk after 4 months of age, and 34% of infants
      were not breastfed at all; 9% of the infants were identified with delays in gross
      motor coordination and 6% with fine motor coordination delays at age 9 months.
      The proportion of infants who mastered the developmental milestones increased
      with duration and exclusivity of breastfeeding. Infants who had never been
      breastfed were 50% more likely to have gross motor coordination delays than
      infants who had been breastfed exclusively for at least 4 months (10.7% vs 7.3%).
      Any breast milk also was positively related to development: infants who had never
      been breastfed were 30% more likely to have gross motor delays than infants who
      were given some breast milk for up to 2 months (10.7% vs 8.4%). The odds ratios
      for gross motor delay were not attenuated after adjustment for biological,
      socioeconomic, or psychosocial factors. Infants who were never breastfed had at
      least a 40% greater likelihood of fine motor delay than infants who were given
      breast milk for a prolonged period. CONCLUSION: Our results suggest that the
      protective effect of breastfeeding on the attainment of gross motor milestones is
      attributable to some component(s) of breast milk or feature of breastfeeding and
      is not simply a product of advantaged social position, education, or parenting
      style, because control for these factors did not explain any of the observed
      association. In contrast, the association between breastfeeding and fine motor
      delay was explained by biological, socioeconomic, and psychosocial factors.

PMID- 16950961
TI  - Exercise tolerance in children and adolescents with musculoskeletal pain in joint
      hypermobility and joint hypomobility syndrome.
AB  - OBJECTIVES: Musculoskeletal pain is a common complaint in a pediatric health care
      practice, but exercise tolerance has never been described in detail in these
      children. Our objectives for this study were to evaluate the maximal exercise
      capacity, including peak heart rate and oxygen consumption, of children with pain
      related musculoskeletal problems, particularly in children with (symptomatic)
      generalized joint hypermobility and hypomobility, during a bicycle ergometry test
      to exhaustion; to evaluate muscle strength, bone mineral density, and sports
      activities in these children and to associate these observations with exercise
      capacity; and to compare these results with reference values. METHODS: Thirty-two
      children (mean age: 12.1 years; SD: 3.4 years; range: 6.2-20.1 years; 62% male)
      with musculoskeletal pain-related syndromes (joint hypermobility syndrome [n =
      13] and joint hypomobility syndrome [n = 19]) participated. The reference group
      consisted of 117 healthy primary school prepubertal children, 167 healthy
      secondary school adolescents, and 98 young adults (249 girls and 133 boys; mean
      age total reference group: 14.5 +/- 4.0 years; range: 8-20.8 years).
      Anthropometry, range of joint motion, muscle strength, bone mineral density
      (speed of sound and broadband ultrasound attenuation), sports activities, and a
      maximal exercise test using an electronically braked cycle ergometer were
      performed, and the patient stopped because of volitional exhaustion. Expired gas
      analysis and heart rate and transcutaneous oxygen saturation by pulse oximetry
      measurements also were performed. RESULTS: Children with joint hypomobility
      syndrome as well as children with joint hypermobility syndrome had a higher mean
      z score (SD) of weight and BMI compared with the reference group. A significantly
      decreased absolute peak oxygen consumption and relative peak oxygen consumption
      in both patient groups was found compared with control subjects. In 14 of 32
      children with a z score relative peak oxygen consumption of less than -2, maximal
      heart rate was significantly decreased compared with 18 children with a z score
      relative peak oxygen consumption of -2 or more (mean [SD] z score speed of sound:
      -1.3 [0.8] vs -0.5 [1.0] and mean [SD] heart rate: 175.9 [11.5] vs 187.5 [10.9],
      respectively). In the total group, a high significant correlation between the z
      score of relative peak oxygen consumption and the z score of the speed of sound
      was found as well as with z score of BMI. Sixteen (50%) of 32 participated in
      sports activities with (mean: 0.9 hours/week; SD: 1.4 hours/week), whereas in the
      control group, 12% of did not participate in sports activities (mean: 2.8
      hours/week; SD: 2.2 hours/week). Children who participated in sports activities
      had a (borderline) significant increased mean (SD) z score of absolute peak
      oxygen consumption and mean (SD) z score of broadband ultrasound attenuation
      compared with children who did not participate in sports activities (-0.3 [1.1]
      vs -1.2 [1.3] and -0.45 [0.8] vs -0.9 [0.5], respectively). CONCLUSIONS: In
      children with musculoskeletal pain-related syndromes, particular in children with
      (symptomatic) generalized joint hypermobility and hypomobility, maximal exercise
      capacity is significantly decreased compared with age- and gender-matched control
      subjects. The most probable explanation for the reduced exercise tolerance in our
      patients is deconditioning.

PMID- 16950962
TI  - Relative benefits of stimulant therapy with OROS methylphenidate versus mixed
      amphetamine salts extended release in improving the driving performance of
      adolescent drivers with attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: Automobile accidents are the leading cause of death among adolescents,
      and collisions are 2 to 4 times more likely to occur among adolescents with
      attention-deficit/hyperactivity disorder. Studies have demonstrated that
      stimulants improve driving performance. This study compared 2 long-acting
      stimulant medications during daytime and evening driving evaluations. METHODS:
      Adolescent drivers with attention-deficit/hyperactivity disorder were compared on
      a driving simulator after taking 72 mg of OROS methylphenidate, 30 mg of mixed
      amphetamine salts extended release, or placebo in a randomized, double-blind,
      placebo-controlled, crossover study design. During laboratory testing,
      adolescents drove a driving simulator at 5:00 pm, 8:00 pm, and 11:00 pm. Driving
      performance was rated by adolescents and investigators. RESULTS: The study
      included 35 adolescent drivers with attention-deficit/hyperactivity disorder (19
      boys/16 girls). The mean age was 17.8 years. The overall Impaired Driving Score
      demonstrated that OROS methylphenidate led to better driving performance compared
      with placebo and mixed amphetamine salts extended release, whereas mixed
      amphetamine salts extended release demonstrated no statistical improvement over
      placebo. Specifically, relative to placebo, OROS methylphenidate resulted in less
      time driving off the road, fewer instances of speeding, less erratic speed
      control, more time executing left turns, and less inappropriate use of brakes.
      OROS methylphenidate and mixed amphetamine salts extended release worked equally
      well for male and female adolescents and equally as well with teenagers who have
      combined and inattentive subtypes of attention-deficit/hyperactivity disorder.
      CONCLUSIONS: This study validates the use of stimulants to improve driving
      performance in adolescents with attention-deficit/hyperactivity disorder. In the
      study, OROS methylphenidate promoted significantly improved driving performance
      compared with placebo and mixed amphetamine salts extended release.

PMID- 16950963
TI  - Matters of spirituality at the end of life in the pediatric intensive care unit.
AB  - OBJECTIVE: Our objective with this study was to identify the nature and the role
      of spirituality from the parents' perspective at the end of life in the PICU and
      to discern clinical implications. METHODS: A qualitative study based on parental
      responses to open-ended questions on anonymous, self-administered questionnaires
      was conducted at 3 PICUs in Boston, Massachusetts. Fifty-six parents whose
      children had died in PICUs after the withdrawal of life-sustaining therapies
      participated. RESULTS: Overall, spiritual/religious themes were included in the
      responses of 73% (41 of 56) of parents to questions about what had been most
      helpful to them and what advice they would offer to others at the end of life.
      Four explicitly spiritual/religious themes emerged: prayer, faith, access to and
      care from clergy, and belief in the transcendent quality of the parent-child
      relationship that endures beyond death. Parents also identified several
      implicitly spiritual/religious themes, including insight and wisdom; reliance on
      values; and virtues such as hope, trust, and love. CONCLUSIONS: Many parents drew
      on and relied on their spirituality to guide them in end-of-life decision-making,
      to make meaning of the loss, and to sustain them emotionally. Despite the
      dominance of technology and medical discourse in the ICU, many parents
      experienced their child's end of life as a spiritual journey. Staff members,
      hospital chaplains, and community clergy are encouraged to be explicit in their
      hospitality to parents' spirituality and religious faith, to foster a culture of
      acceptance and integration of spiritual perspectives, and to work collaboratively
      to deliver spiritual care.

PMID- 16950964
TI  - Why are Latinos the most uninsured racial/ethnic group of US children? A
      community-based study of risk factors for and consequences of being an uninsured
      Latino child.
AB  - BACKGROUND: Latinos continue to be the most uninsured racial/ethnic group of US
      children, but not enough is known about the risk factors for and consequences of
      not being insured in Latino children. OBJECTIVE: [corrected] The objective of
      this study was to identify the risk factors for and consequences of being
      uninsured in Latino children. METHODS: A cross-sectional survey was conducted of
      parents at urban, predominantly Latino community sites, including supermarkets,
      beauty salons, and laundromats. Parents were asked 76 questions on access and
      health insurance. RESULTS: Interviews were conducted of 1100 parents, 900 of whom
      were Latino. Uninsured Latino children were significantly more likely than
      insured Latino children to be older (mean age: 9 vs 7 years) and poor (89% vs
      72%) and to have parents who are limited in English proficiency (86% vs 65%), non
      US citizens (87% vs 64%), and both employed (35% vs 27%). Uninsured Latinos were
      significantly less likely than their insured counterparts to have a regular
      physician (84% vs 99%) and significantly more likely not to be brought in for
      needed medical care because of expense, lack of insurance, difficulty making
      appointments, inconvenient office hours, and cultural issues. In multivariable
      analyses, parents who are undocumented or documented immigrants, both parents
      working, the child's age, and the $4000 to $9999 and $15000 to $19999 family
      income quintiles were the only factors that were significantly associated with a
      child's being uninsured; neither Latino ethnicity nor any other of 6 variables
      were associated with being uninsured. Compared with insured Latino children,
      uninsured Latino children had 23 times the odds of having no regular physician
      and were significantly more likely not to be brought in for needed medical care
      because of expense, lack of health insurance, difficulty making appointments, and
      cultural barriers. CONCLUSIONS: After adjustment, parental noncitizenship, having
      2 parents work, low family income, and older child age are associated with being
      an uninsured child, but Latino ethnicity is not. The higher prevalence of other
      risk factors seems to account for Latino children's high risk for being
      uninsured. Uninsured Latino children are significantly more likely than insured
      Latino children to have no regular physician and not to get needed medical care
      because of expense, lack of health insurance, difficulty making appointments, and
      cultural barriers. These findings indicate specific high-risk populations that
      might benefit most from targeted Medicaid and State Child Health Insurance
      Program outreach and enrollment efforts.

PMID- 16950965
TI  - Chronic snoring and sleep in children: a demonstration of sleep disruption.
AB  - OBJECTIVE: Chronic snoring that does not adhere to the criteria for a diagnosis
      of obstructive sleep apnea syndrome may be associated with learning and
      behavioral problems. We investigated the sleep structure of chronic snorers who
      had an apnea-hypopnea index of < 1 event per hour and analyzed the cyclic
      alternating pattern. METHODS: Fifteen successively seen chronic snorers (9.8 +/-
      4 years) with an apnea-hypopnea index of <1 and 15 aged-matched control subjects
      (10.3 +/- 5 years) underwent an investigation of their sleep with the
      determination of non-apneic-hypopneic breathing abnormalities polysomnographic
      scoring using current criteria and analysis of the cyclic alternating pattern.
      RESULTS: Chronic snorers have evidence of flow limitations and tachypnea during
      sleep even if they do not present with apneas, hypopneas, and decrease in oxygen
      saturations. They also present with abnormal cyclic alternating pattern rates and
      changes in phase A of cyclic alternating pattern compared with control subjects.
      CONCLUSIONS: An apnea-hypopnea index value cannot be the sole determinant in
      evaluating sleep-disordered breathing in children. Children who have chronic
      snoring and do not respond to the criteria for obstructive sleep apnea syndrome
      can present with an abnormal sleep electroencephalogram as evidenced by a
      significant increase in cyclic alternating pattern rates, with a predominance of
      abnormalities in slow wave sleep.

PMID- 16950966
TI  - Age of alcohol-dependence onset: associations with severity of dependence and
      seeking treatment.
AB  - OBJECTIVE: We explored whether people who become alcohol dependent at younger
      ages are more likely to seek alcohol-related help or treatment or experience
      chronic relapsing dependence. METHODS: In 2001-2002 the National Institute on
      Alcohol Abuse and Alcoholism completed a face-to-face interview survey with a
      multistage probability sample of 43,093 adults aged > or = 18, with a response
      rate of 81%. We focused on 4778 persons diagnosable as alcohol dependent ever in
      their lives using Diagnositic and Statistical Manual of Mental Disorders, Fourth
      Edition criteria. Logistic regression examined whether respondents ever sought
      alcohol-related help or treatment, controlling for respondent demographics,
      number of dependence symptoms experienced, smoking and illicit drug use,
      childhood antisocial personality and depression, family history of alcoholism,
      and age of drinking onset. RESULTS: Of persons ever alcohol dependent, 15% were
      diagnosable before age 18, 47% before age 21, and two thirds before age 25.
      Twenty-eight percent reported > or = 2 dependence episodes, 45% experienced an
      episode exceeding 1 year, and 34% reported 6 or 7 dependence criteria. Relative
      to those first alcohol dependent at > or = 30 years, 21% of those ever dependent,
      the odds of ever seeking help were lower among those first dependent before ages
      18, 20, and 25. Yet, persons first dependent at < or = 25 years had significantly
      greater odds of experiencing multiple dependence episodes, episodes exceeding 1
      year, and more dependence symptoms. Analyses indicated that the previously
      reported increased odds that persons who start to drink at an early age develop
      features of chronic relapsing dependence may have resulted from early drinkers
      being more likely to develop alcohol dependence at younger ages. This, in turn,
      increased their odds of experiencing multiple and longer episodes of alcohol
      dependence with more symptoms. CONCLUSIONS: Adolescents need to be screened and
      counseled about alcohol, and treatment services should be reinforced by programs
      and policies to delay age of first alcohol dependence.

PMID- 16950967
TI  - Immunosuppressive therapy does not prevent the occurrence of immunoglobulin E
      mediated allergies in children and adolescents with organ transplants.
AB  - BACKGROUND: Allogeneic organ transplantation has become a common procedure in
      acute and chronic organ failure. The major limitation, rejection of the allograft
      by the host's immune system, can be limited by various immunosuppressive drugs
      that target the adaptive T-cell response. Most of these drugs are used in the
      treatment of allergic diseases as well, suggesting that transplant recipients
      under long-term immunosuppressive therapy should not develop any sensitizations
      or at least not show any clinical signs of allergy. Surprisingly, organ
      transplanted children and adults do report symptoms of type 1 allergies, such as
      allergic rhinoconjunctivitis, bronchial asthma, and food allergies. Thus far,
      mainly case reports and series on the occurrence of allergy after orthotopic
      liver transplantation exist. OBJECTIVE: Our purpose with this study was to
      evaluate in a cross-sectional design the prevalence of immunoglobulin E-mediated
      sensitizations and type 1 allergies in solid organ-transplanted children and
      adolescents and to identify risk factors. METHODS: Seventy-eight organ
      transplanted subjects (50 kidney, 9 lung, 19 liver; mean age: 14.06 +/- 5.94
      years; range 1.42 to 24.25 years) were studied by standardized interviews
      (modified International Study of Asthma and Allergies in Childhood [ISAAC]
      criteria), skin-prick tests, and measurement of specific and total serum
      immunoglobulin E. RESULTS: Nineteen patients (24.4%) were found to be sensitized
      to > or = 1 common inhalant or food allergens, as reflected by elevated specific
      immunoglobulin E levels and/or positive skin-prick test results, and 8 subjects
      (10.3%) additionally reported a corresponding present history of atopic diseases.
      No severe anaphylactic reactions were reported. No statistically significant
      associations with gender, kind of transplanted organ, distinct immunosuppressive
      therapies, and age at time of transplantation or age at investigation were found
      (chi2 test, Fisher's exact test, and Wilcoxon rank-sum test, respectively).
      Multiple logistic-regression analysis did not identify any independent risk
      factor either. CONCLUSION: This study demonstrates that therapeutic
      immunosuppression does not control sensitizations and clinical manifestation of
      type 1 allergies in organ-transplanted children and adolescents.

PMID- 16950968
TI  - Maternal depression and violence exposure: double jeopardy for child school
      functioning.
AB  - OBJECTIVE: The goal was to determine how violence exposure affects the
      relationship between maternal depression, cognitive ability, and child behavior.
      METHODS: A multivariate regression analysis of data for a nationally
      representative sample of kindergarten students was performed. Maternal depression
      and violence exposure were measured with standardized parent interviews.
      Standardized T scores were derived from direct testing of children in reading,
      mathematics, and general knowledge; child behavior was reported by teachers.
      RESULTS: A total of 9360 children had neither maternal depression nor violence
      exposure, 779 violence only, 1564 depression only, and 380 both. Maternal
      depression alone was associated with poorer mean T scores for reading,
      mathematics, and general knowledge. However, this effect was attenuated by nearly
      25% for reading and general knowledge with adjustment for violence. Children with
      concurrent exposure to depression and violence had lower mean T scores for
      reading, mathematics, and general knowledge, as well as more-concerning
      behaviors, than did those exposed to either factor alone. Across all outcome
      measures, boys seemed more affected than girls. CONCLUSIONS: Violence compounds
      the effect of maternal depression on school functioning and behavior. Research
      and intervention planning for children affected by maternal depression should
      consider violence exposure.

PMID- 16950969
TI  - Smoking prevention and cessation intervention delivery by pediatric providers, as
      assessed with patient exit interviews.
AB  - OBJECTIVE: The goal was to evaluate the degree to which a smoking prevention and
      cessation intervention was delivered by providers to adolescents in the pediatric
      office setting. METHODS: Eight pediatric clinics in central Massachusetts were
      assigned randomly to either a special intervention (brief pediatric provider
      delivered intervention plus peer counseling) or the usual care condition.
      Subjects (n = 2710) were adolescents 13 to 17 years of age, both smokers (smoked
      in the past 30 days) and nonsmokers/former smokers. The degree to which smoking
      prevention and treatment interventions were delivered by providers was assessed
      through patient exit interviews with adolescents after their clinic visits;
      interviews assessed the occurrence of 10 possible intervention steps. RESULTS:
      The percentage of providers engaging in the smoking interventions differed
      significantly between the special intervention and usual care conditions,
      according to adolescent reports in the patient exit interviews. For
      nonsmokers/former smokers, overall patient exit interview scores were 7.24 for
      the special intervention condition and 4.95 for the usual care condition. For
      current smokers, overall patient exit interview scores were 8.40 and 6.24 for the
      special intervention and usual care conditions, respectively. Intervention
      fidelity of special intervention providers was 72.2% and 84.0% for
      nonsmokers/former smokers and current smokers, respectively. CONCLUSIONS:
      Pediatric providers who receive training and reminders to deliver a brief smoking
      prevention and cessation intervention to adolescents in the context of routine
      pediatric primary care practice can do so feasibly and with a high degree of
      fidelity to the intervention protocol.

PMID- 16950970
TI  - Role of pediatric health care professionals in the provision of parenting advice:
      a qualitative study with mothers from 4 minority ethnocultural groups.
AB  - OBJECTIVE: This study's aim was to elicit the perspectives of minority parents on
      their expectations of pediatric health care providers as a source of advice on
      "raising their child" and whether they would seek advice from these providers. A
      secondary aim was to demonstrate the value of qualitative methods for assessing
      parental attitudes in pediatric research. METHODS: Mothers with children between
      3 and 12 years of age who identified themselves as African American, Jamaican,
      Haitian, or Puerto Rican were recruited from community sites. Audiotaped focus
      groups were conducted by trained moderators using an interview guide, to obtain
      the perspectives of the participants regarding the role of pediatric providers in
      the provision of parenting advice. RESULTS: Ninety-one mothers participated in a
      total of 20 focus groups, with 4 to 6 discussions per ethnocultural group. The
      focus groups revealed that, in general, parents do not look to child health care
      providers for advice on raising their children. The identified themes emphasized
      the importance of the relationship between providers and families. A few parents
      had the type of relationship within which the pediatrician already functioned as
      a provider of parenting advice. Physicians were considered skilled in the
      maintenance of physical health. The parents expressed a desire to receive more
      anticipatory guidance on developmental and behavioral stages and milestones.
      Pediatricians also served specific administrative functions valued by parents.
      CONCLUSIONS: Minority parents of preschool-aged and school-aged children do not
      view the primary care provider's role as including the provision of parenting
      advice. Expectations must be modified to enable health care professionals to
      function effectively in the role of advisor regarding parenting issues.

PMID- 16950971
TI  - Food insecurity and the risks of depression and anxiety in mothers and behavior
      problems in their preschool-aged children.
AB  - OBJECTIVES: We sought to determine if the prevalence of depression and anxiety in
      mothers and the prevalence of behavior problems in preschool-aged children are
      more common when mothers report being food insecure. METHODS: A cross-sectional
      survey of 2870 mothers of 3-year-old children was conducted in 2001-2003 in 18
      large US cities. On the basis of the adult food-security scale calculated from
      the US Household Food Security Survey Module, mothers were categorized into 3
      levels: fully food secure, marginally food secure, and food insecure. The 12
      month prevalence in mothers of a major depressive episode and generalized anxiety
      disorder was assessed by the Composite International Diagnostic Interview-Short
      Form. A child behavior problem in > or = 1 of 3 domains (aggressive,
      anxious/depressed, or inattention/hyperactivity) was based on the Child Behavior
      Checklist. RESULTS: Seventy-one percent of the respondents were fully food
      secure, 17% were marginally food secure, and 12% were food insecure. After
      adjustment for sociodemographic factors plus maternal physical health, alcohol
      use, drug use, prenatal smoking, and prenatal physical domestic violence, the
      percentage of mothers with either major depressive episode or generalized anxiety
      disorder increased with increasing food insecurity: 16.9%, 21.0%, and 30.3%
      across the 3 levels. Among children, after further adjustment for maternal major
      depressive episode and generalized anxiety disorder, the percentage with a
      behavior problem also increased with increasing food insecurity: 22.7%, 31.1%,
      and 36.7%. CONCLUSIONS: Mental health problems in mothers and children are more
      common when mothers are food insecure, a stressor that can potentially be
      addressed by social policy.

PMID- 16950972
TI  - Youth tobacco use: a global perspective for child health care clinicians.
AB  - Tobacco dependence, responsible for approximately 4 million annual deaths
      worldwide, is considered to be a "pediatric disease." The smoking epidemic is
      spreading rapidly in developing countries. Factors contributing to youth smoking
      in developing countries include cultural traditions, tobacco's easy accessibility
      and moderate pricing, peer and family influences, and tobacco companies'
      advertisements and promotional activities. Secondhand tobacco smoke exposure is a
      substantial problem that causes increased rates of pneumonia, otitis media,
      asthma, and other short- and long-term pediatric conditions. Parental tobacco use
      results in children's deprivation of essential needs such as nutrition and
      education. In this article we review contemporary evidence with respect to the
      etiology of nicotine dependence among youth, the forms of youth tobacco products
      worldwide, global youth tobacco-control efforts to date, medical education
      efforts, and child health care clinicians' special role in youth tobacco-control
      strategies. In addition, we provide a review of currently available funding
      opportunities for development and implementation of youth tobacco-control
      programs.

PMID- 16950973
TI  - Newborn screening fact sheets.
AB  - Newborn screening fact sheets were last revised in 1996 by the American Academy
      of Pediatrics Committee on Genetics. This revision was prompted by advances in
      the field since 1996, including technologic innovations, as well as greater
      appreciation of ethical issues such as those surrounding informed consent. The
      following disorders are discussed in this revision of the newborn screening fact
      sheets: biotinidase deficiency, congenital adrenal hyperplasia, congenital
      hearing loss, congenital hypothyroidism, cystic fibrosis, galactosemia,
      homocystinuria, maple syrup urine disease, medium-chain acyl-coenzyme A
      dehydrogenase deficiency, phenylketonuria, sickle cell disease and other
      hemoglobinopathies, and tyrosinemia. A series of topics related to newborn
      screening is discussed in a companion publication to this electronic publication
      of the fact sheets (available at:
      www.pediatrics.org/cgi/content/full/118/3/1304). These topics are newborn
      screening as a public health system; factors contributing to the need for review
      of the newborn screening system; informed consent; tandem mass spectrometry; DNA
      analysis in newborn screening; status of newborn screening in the United States;
      and the effect of sample timing, preterm birth, diet, transfusion, and total
      parenteral nutrition on newborn screening results.

PMID- 16950974
TI  - Trends in sunburns, sun protection practices, and attitudes toward sun exposure
      protection and tanning among US adolescents, 1998-2004.
AB  - BACKGROUND: Sun exposure in childhood is an important risk factor for developing
      skin cancer as an adult. Despite extensive efforts to reduce sun exposure among
      the young, there are no population-based data on trends in sunburns and sun
      protection practices in the young. The aim of this study was to describe
      nationally representative trend data on sunburns, sun protection, and attitudes
      related to sun exposure among US youth. METHODS: Cross-sectional telephone
      surveys of youth aged 11 to 18 years in 1998 (N = 1196) and in 2004 (N = 1613)
      were conducted using a 2-stage sampling process to draw population-based samples.
      The surveys asked identical questions about sun protection, number of sunburns
      experienced, and attitudes toward sun exposure. Time trends were evaluated using
      pooled logistic regression analysis. RESULTS: In 2004, 69% of subjects reported
      having been sunburned during the summer, not significantly less than in 1998
      (72%). There was a significant decrease in the percentage of those aged 11 to 15
      years who reported sunburns and a nonsignificant increase among the 16- to 18
      year-olds. The proportion of youth who reported regular sunscreen use increased
      significantly from 31% to 39%. Little change occurred in other recommended sun
      protection practices. CONCLUSIONS: A small reduction in sunburn frequency and
      modest increases in sun protection practices were observed among youth between
      1998 and 2004, despite widespread sun protection campaigns. Nevertheless, the
      decrease in sunburns among younger teens may be cause for optimism regarding
      future trends. Overall, there was rather limited progress in improving sun
      protection practices and reducing sunburns among US youth between 1998 and 2004.

PMID- 16950975
TI  - National impact of universal childhood immunization with pneumococcal conjugate
      vaccine on outpatient medical care visits in the United States.
AB  - BACKGROUND: Since introduction of the heptavalent pneumococcal conjugate vaccine
      in the United States in 2000, rates of invasive pneumococcal disease have
      declined. However, the national impact of heptavalent pneumococcal conjugate
      vaccine on pneumonia and otitis media remains unknown. OBJECTIVES: We compared
      national rates of outpatient visits for pneumonia and otitis media in children
      before and after heptavalent pneumococcal conjugate vaccine introduction.
      METHODS: Rates of ambulatory visits for pneumococcal and nonspecific pneumonia,
      otitis media, and other acute respiratory infections were compared before (1994
      1999) and after (2002-2003) heptavalent pneumococcal conjugate vaccine
      introduction using the National Ambulatory Medical Care Survey and the National
      Hospital Ambulatory Medical Care Survey. To evaluate vaccine effects while
      accounting for temporal variability, ratios of pneumococcal-related disease rates
      in children < 2 years old (vaccine target population) and in children 3 to 6
      years old (not routinely vaccinated) were evaluated using a Poisson regression
      analysis. For children < 2 years old, the differences between observed and
      expected rates were the estimated vaccine effects. RESULTS: After the
      introduction of heptavalent pneumococcal conjugate vaccine, otitis media visit
      rates declined by 20% in children aged < 2 years. This decline represented 246
      fewer otitis media visits per 1000 children aged < 2 years annually. There were
      no significant decreases in outpatient visit rates for pneumonia or other acute
      respiratory infections for children aged < 2 years. CONCLUSIONS: After
      heptavalent pneumococcal conjugate vaccine introduction, national rates of otitis
      media visits declined significantly in children < 2 years old. Persistence of
      this trend will produce a significant reduction of the otitis media burden and
      further enhance the cost-effectiveness of heptavalent pneumococcal conjugate
      vaccine.

PMID- 16950976
TI  - Community-acquired Staphylococcus aureus infections in term and near-term
      previously healthy neonates.
AB  - BACKGROUND: Community-acquired, methicillin-resistant Staphylococcus aureus
      infections are increasing among children. OBJECTIVE: Our goal is to describe the
      clinical presentation of neonatal community-acquired S aureus disease and provide
      molecular analyses of the infecting isolates. PATIENTS AND METHODS: We
      retrospectively reviewed the demographics and hospital course of term and near
      term previously healthy neonates, < or = 30 days of age, with community-acquired
      S aureus infections presenting after nursery discharge between August 2001 and
      March 2005 at Texas Children's Hospital. Prospectively collected isolates were
      characterized by pulsed-field gel electrophoresis, staphylococcal cassette
      chromosome mec type, and the presence of PVL genes. RESULTS: Of 89 S aureus
      infections, 61 were methicillin-resistant S aureus; S aureus infections increased
      each year. Methicillin-resistant S aureus infections increased from 10 of 20 to
      30 of 36 infections from 2002 to 2004. Most subjects, 65 of 89, were male.
      Symptoms began at 7 to 12 days of age for 26 of 45 male infants with methicillin
      resistant S aureus. Most infections, 77 of 89, involved skin and soft tissue; 28
      of 61 methicillin-resistant S aureus versus 7 of 28 methicillin-susceptible S
      aureus infections required drainage. Invasive manifestations included shock,
      musculoskeletal and urinary tract infection, perinephric abscess, bacteremia,
      empyema/lung abscess, and a death. Maternal S aureus or skin-infection history
      occurred with 13 of 61 methicillin-resistant S aureus versus 1 of 28 methicillin
      susceptible S aureus infections. The predominant community clone, USA300 (PVL
      genes +), accounted for 55 of 57 methicillin-resistant S aureus and 3 of 25
      methicillin-susceptible S aureus isolates. CONCLUSIONS: Community-acquired
      methicillin-resistant S aureus is a substantial and increasing proportion of S
      aureus infections in previously healthy neonates. Male infants 7 to 12 days of
      age are affected most often. Neonatal community-acquired S aureus infection may
      be associated with concurrent maternal infection. USA300 is the predominant clone
      among these neonatal isolates in our region.

PMID- 16950977
TI  - Prospective study of infantile hemangiomas: clinical characteristics predicting
      complications and treatment.
AB  - OBJECTIVES: Infantile hemangiomas are the most common tumor of infancy. Risk
      factors for complications and need for treatment have not been studied previously
      in a large prospective study. This study aims to identify clinical
      characteristics associated with complications and the need for therapeutic
      intervention. PATIENTS AND METHODS: We conducted a prospective cohort study at 7
      US pediatric dermatology clinics with a consecutive sample of 1058 children, aged
      < or = 12 years, with infantile hemangiomas enrolled between September 2002 and
      October 2003. A standardized questionnaire was used to collect data on each
      patient and each hemangioma, including clinical characteristics, complications,
      and treatment. RESULTS: Twenty-four percent of patients experienced complications
      related to their hemangioma(s), and 38% of our patients received some form of
      treatment during the study period. Hemangiomas that had complications and
      required treatment were larger and more likely to be located on the face.
      Segmental hemangiomas were 11 times more likely to experience complications and 8
      times more likely to receive treatment than localized hemangiomas, even when
      controlled for size. CONCLUSIONS: Large size, facial location, and/or segmental
      morphology are the most important predictors of poor short-term outcomes as
      measured by complication and treatment rates.

PMID- 16950978
TI  - Neonatal screening for cystic fibrosis does not affect time to first infection
      with Pseudomonas aeruginosa.
AB  - OBJECTIVE: Newborn screening for cystic fibrosis was introduced in the Piedmont
      region of Italy in the year 2000. Our aim with this study was to estimate the
      effect of newborn screening on the risk of Pseudomonas aeruginosa infection at
      the regional cystic fibrosis pediatric reference center. METHODS: The time to
      first infection with P aeruginosa within the historical cohort of cystic fibrosis
      children diagnosed between January 1, 1997, and June 30, 2004, was investigated,
      comparing survival functions and the adjusted hazard ratio of children diagnosed
      before and after newborn screening introduction. The role of pancreatic
      insufficiency was also concurrently investigated. RESULTS: Overall, 71 children
      diagnosed with cystic fibrosis were identified, 27 cases were clinically
      diagnosed before newborn screening introduction, and 5 of them presented with
      meconium ileus, whereas 44 were identified by newborn screening. Among them 35
      needed pancreatic enzyme supplementation, whereas 34 children were infected with
      P aeruginosa. Both the nonparametric and semiparametric survival estimates failed
      to show any significant increase in the risk of P aeruginosa infection among
      screened children compared with historical controls. However, the median time
      from cystic fibrosis diagnosis to P aeruginosa infection among screened children
      was significantly shorter (183 vs 448 days). Children with impaired pancreatic
      function were at high risk of P aeruginosa infection. CONCLUSIONS: The results of
      the study suggest that health authorities should regard newborn screening for
      cystic fibrosis as an opportunity to improve care and outcomes among affected
      children and shift the focus from whether it is appropriate to screen to how to
      optimize biomedical and psychosocial outcomes of screening.

PMID- 16950979
TI  - Cost-effectiveness of 4 neonatal screening strategies for cystic fibrosis.
AB  - OBJECTIVES: The purpose of this work was to assess the costs of 4 neonatal
      screening strategies for cystic fibrosis in relation to health effects. In each
      strategy, the first test was the measurement of serum concentration of
      immunoreactive trypsin. The second step consisted of either a second
      immunoreactive trypsin test (strategy 1) or a multiple mutation analysis
      (strategy 2). In strategies 3 and 4, a third step was added to strategy 2: a
      second immunoreactive trypsin test (strategy 3) or an extended mutation analysis
      of the cystic fibrosis gene, that is, a denaturing gradient gel electrophoresis
      analysis (strategy 4). METHODS: We conducted an economic-modeling exercise in the
      Netherlands based on published data and expert opinions. Subjects were a
      hypothetical cohort of 200 000 neonates, the approximate number of children born
      annually in the Netherlands, and we assessed the costs and number of life-years
      gained as a result of neonatal screening for cystic fibrosis. The costs and
      effects of changes in reproductive decisions because of neonatal screening were
      also assessed. RESULTS: Immunoreactive trypsin + immunoreactive trypsin had the
      most favorable cost-effectiveness ratio of 24,800 euro per life-year gained.
      Immunoreactive trypsin + DNA + denaturing gradient gel electrophoresis achieved
      more health effects than immunoreactive trypsin + DNA + immunoreactive trypsin at
      lower cost. The incremental costs per life-year gained of the immunoreactive
      trypsin + DNA + denaturing gradient gel electrophoresis strategy compared with
      the immunoreactive trypsin + immunoreactive trypsin strategy were 130,700 euro,
      whereas the incremental costs of the immunoreactive trypsin + DNA strategy
      compared with the immunoreactive trypsin + DNA + denaturing gradient gel
      electrophoresis strategy were 2,154,300 euro. When changes in reproductive
      decisions as a result of neonatal screening are also taken into account, neonatal
      screening for cystic fibrosis may lead to financial savings of approximately 1.8
      million euro annually, depending on the screening strategy used. CONCLUSIONS:
      Cystic fibrosis screening for neonates is a good economic option, and positive
      health effects can also be expected. Immunoreactive trypsin + immunoreactive
      trypsin and immunoreactive trypsin + DNA + denaturing gradient gel
      electrophoresis are the most cost-effective strategies.

PMID- 16950980
TI  - Hospitalizations of newborns with folate-sensitive birth defects before and after
      fortification of foods with folic acid.
AB  - CONTEXT: The prevalence of neural tube defects is reduced in populations of women
      who receive folic acid supplementation. Since 1998, grain products in the United
      States have been fortified with folic acid. Fortification may have additional
      benefits by reducing the national prevalence of newborn hospitalizations for
      other folate-sensitive birth defects. OBJECTIVE: Our purpose with this work was
      to compare rates of hospitalizations of newborns with folate-sensitive birth
      defects before and after implementation of fortification of grains. METHOD:
      National hospital discharge data from the Healthcare Cost and Utilization Project
      were used to compute rates of newborn hospitalizations for selected birth defects
      per 10,000 live births in the United States. Newborn hospitalization rates
      involving congenital anomalies recognizable at birth were analyzed for 5 years
      before fortification of grains and 5 years after fortification. Additional
      analyses compared changes in newborn hospitalization rates for birth defects by
      race/ethnicity, income, insurance status, and region of the country. RESULTS:
      Newborn hospitalization rates for spina bifida decreased 21% from 1993-1997 to
      1998-2002. Newborn hospitalization rates also decreased for anencephaly (20%) and
      limb-reduction defects (4%). Decline in hospitalizations for spina bifida
      occurred more often among Hispanic newborns (33%) than among white (13%) or black
      (21%) newborns. Decline in limb-reduction defects was seen primarily among blacks
      (11%). Findings using hospitalization data were similar to recent reports using
      birth defect surveillance systems with the exception of findings for orofacial
      clefts and conotruncal heart defects. No reductions were noted in newborn
      hospitalizations for these anomalies. CONCLUSIONS: Results from this ecological
      study fail to demonstrate substantial declines in newborn hospitalizations beyond
      those anticipated from a reduction in neural tube defects. The society-wide
      impact of the fortification program on birth defects and other health conditions
      should continue to be monitored.

PMID- 16950981
TI  - Are encephaloceles neural tube defects?
AB  - OBJECTIVE: Encephalocele is classified as a neural tube defect, but questions
      have been raised regarding whether its epidemiological characteristics are
      similar to those of other neural tube defects. DESIGN: We compared
      characteristics of temporal trends in, and the impact of folic acid grain
      fortification on, the prevalence of encephalocele, spina bifida, and anencephaly
      using data from the Metropolitan Atlanta Congenital Defects Program, a population
      based birth defects surveillance system. Prevalences of encephalocele, spina
      bifida, and anencephaly were compared by maternal age, gender, race, birth
      weight, ascertainment period (1968-1981, 1982-1993, or 1994-2002), and
      fortification period (1994-1996 [prefortification] and 1998-2002
      [postfortification]) using prevalence ratios with 95% confidence intervals.
      Temporal trends were assessed using Poisson and negative binomial regression
      models. RESULTS: Prevalence rates of encephalocele (n = 167), spina bifida (n =
      650), and anencephaly (n = 431) were 1.4, 5.5, and 3.7 per 10 000 live births,
      respectively. Encephalocele was similar to anencephaly in showing an increased
      prevalence among girls and multiple gestation pregnancies and to spina bifida and
      anencephaly in an annual prevalence decrease between 1968 and 2002 (-1.2% for
      encephalocele, -4.2% for spina bifida, and -3.6% for anencephaly). With
      fortification, prevalence decreased for spina bifida but not significantly for
      encephalocele or anencephaly. CONCLUSIONS: Encephalocele shows more similarities
      to spina bifida or anencephaly than it shows differences with respect to
      characteristics, temporal trend, and impact of fortification. Additional studies
      should be done to explore the etiologic heterogeneity of encephalocele using
      better markers of folate status and a wider range of risk factors.

PMID- 16950982
TI  - Enzyme-replacement therapy with agalsidase alfa in children with Fabry disease.
AB  - CONTEXT: Fabry disease is an X-linked multisystem disorder. Enzyme-replacement
      therapy in adults has limited efficacy in treating major sequelae of advanced
      Fabry disease, such as kidney failure or stroke. This prompted a study of the
      safety and efficacy of enzyme replacement at an earlier stage of Fabry disease.
      OBJECTIVES: Our purpose with this work was to evaluate safety and to explore
      efficacy of enzyme treatment with agalsidase alfa in pediatric patients with
      Fabry disease. METHODS: We conducted a 6-month open-label study at 3 tertiary
      care centers with 24 children (19 boys and 5 girls) with a mean age of 11.8
      (range: 6.5-18) years, to examine safety parameters, including infusion reactions
      and antiagalsidase alfa antibodies. RESULTS: Agalsidase alfa was well tolerated,
      and all of the patients completed the study. Six boys and 1 girl had mild-to
      moderate infusion reactions. One boy developed transient immunoglobulin G
      antibodies against agalsidase alfa. The boys showed a significant reduction in
      plasma globotriaosylceramide on treatment. Mean estimated glomerular filtration
      rate, cardiac structure, and function were normal and did not change over 26
      weeks. Heart rate variability, as determined by 2-hour ambulatory monitoring, was
      decreased in the boys compared with the girls at baseline. All indices of heart
      rate variability improved significantly in the boys. Three patients with
      anhidrosis, as determined by quantitative sudomotor axon reflex testing,
      developed sweating. Six of 11 patients could reduce or cease their use of
      antineuropathic analgesics. CONCLUSIONS: Enzyme replacement with agalsidase alfa
      was safe in this study. The exploratory efficacy analysis documented increased
      clearance of globotriaosylceramide and improvement of autonomic function.
      Prospective long-term studies are needed to assess whether enzyme replacement
      initiated early in patients with Fabry disease is able to prevent major organ
      failure in adulthood.

PMID- 16950983
TI  - Child maltreatment in the United States: prevalence, risk factors, and adolescent
      health consequences.
AB  - OBJECTIVES: The purpose of this study was to estimate the prevalence of child
      maltreatment in the United States and examine its relationship to
      sociodemographic factors and major adolescent health risks. METHODS: The National
      Longitudinal Study of Adolescent Health is a prospective cohort study following a
      national sample of adolescents into adulthood. The wave III interview, completed
      by 15 197 young adults in 2001-2002 (77.4% response rate), included retrospective
      measures of child maltreatment. We used these measures to estimate the prevalence
      of self-reported supervision neglect, physical neglect, physical assault, and
      contact sexual abuse during childhood. Next, we investigated the relationship
      between sociodemographic characteristics and maltreatment. Finally, we examined
      the association between child maltreatment and adolescent self-rated health;
      overweight status; depression; cigarette, alcohol, marijuana, and inhalant use;
      and violent behavior. RESULTS: Having been left home alone as a child, indicating
      possible supervision neglect, was most prevalent (reported by 41.5% of
      respondents), followed by physical assault (28.4%), physical neglect (11.8%), and
      contact sexual abuse (4.5%). Each sociodemographic characteristic was associated
      with > or = 1 type of maltreatment, and race/ethnicity was associated with all 4.
      Each type of maltreatment was associated with no fewer than 8 of the 10
      adolescent health risks examined. CONCLUSIONS: Self-reported childhood
      maltreatment was common. The likelihood of maltreatment varied across many
      sociodemographic characteristics. Each type of maltreatment was associated with
      multiple adolescent health risks.

PMID- 16950984
TI  - Effect of maternal smoking during pregnancy on offspring's cognitive ability:
      empirical evidence for complete confounding in the US national longitudinal
      survey of youth.
AB  - BACKGROUND: Numerous studies have reported that maternal cigarette smoking during
      pregnancy is related to lower IQ scores in the offspring. Confounding is a
      crucial issue in interpreting this association. METHODS: In the US National
      Longitudinal Survey of Youth 1979, IQ was ascertained serially during childhood
      using the Peabody Individual Achievement Test, the total score for which
      comprises results on 3 subtests: mathematics, reading comprehension, and reading
      recognition. Maternal IQ was assessed by using the Armed Forces Qualification
      Test. There were 5578 offspring (born to 3145 mothers) with complete information
      for maternal smoking habits, total Peabody Individual Achievement Test score, and
      covariates. RESULTS: The offspring of mothers who smoked > or = 1 pack of
      cigarettes per day during pregnancy had an IQ score (Peabody Individual
      Achievement Test total) that was, on average, 2.87 points lower than children
      born to nonsmoking mothers. Separate control for maternal education (0.27-IQ
      point decrement) and, to a lesser degree, maternal IQ (1.51-IQ-point decrement)
      led to marked attenuation of the maternal-smoking-offspring-IQ relation. A
      similar pattern of results was seen when Peabody Individual Achievement Test
      subtest results were the outcomes of interest. The only exception was the Peabody
      Individual Achievement Test mathematics score, in which adjusting for maternal IQ
      essentially led to complete attenuation of the maternal-smoking-offspring-IQ
      gradient (0.66-IQ-point decrement). The impact of controlling for physical,
      behavioral, and other social indices was much less pronounced than for maternal
      education or IQ. CONCLUSIONS: These findings suggest that previous studies that
      did not adjust for maternal education and/or IQ may have overestimated the
      association of maternal smoking with offspring cognitive ability.

PMID- 16950985
TI  - Detection of impaired growth of the corpus callosum in premature infants.
AB  - OBJECTIVE: There is an urgent need for a bedside method to assess the
      effectiveness of neonatal therapies designed to improve cerebral development in
      very low birth-weight infants. The aim of this study was to assess the impact of
      preterm birth on the serial growth of the corpus callosum and how soon it could
      be detected after birth with cranial ultrasound. METHODS: We recruited 61 very
      low birth-weight infants admitted to a single regional level III NICU from 1998
      to 2000. Study infants had 2 cranial sonograms > or = 7 days apart in the first 2
      weeks of life and further sonograms at 6 weeks and at term equivalent. At each
      time point, the length of the corpus callosum and cerebellar vermis was measured
      on midline sagittal images, with growth rates calculated in millimeters per day.
      We compared growth of corpus callosum and cerebellar vermis in individuals,
      between birth age groups, and with corrected gestational age. We used antenatal
      growth rate of the corpus callosum of 0.2 to 0.27 mm/day as a reference.
      Relationships between corpus callosum growth rates and neurodevelopmental outcome
      at 2 years of age (corrected) were also examined. RESULTS: Growth of the corpus
      callosum was normal in most infants during the first 2 weeks of life but slowed
      after this (0.21 mm/day from 0-2 weeks vs 0.11 mm/day for weeks 2-6). Slowing of
      corpus callosum growth below expected reference range was consistently detectable
      by age 6 weeks for 96% of infants born between 23 and 33 weeks' gestation.
      Although some improvement in growth rate was observed for 15% of infants after 6
      weeks, this was confined to infants born after 28 weeks. Vermis length correlated
      strongly with corpus callosum length. By 2 years of age, serious motor delay and
      cerebral palsy were associated with poorer growth of the length of the corpus
      callosum between 2 and 6 weeks after birth. CONCLUSIONS: The effect of preterm
      birth on growth of the corpus callosum is detectable by 6 weeks after delivery in
      preterm infants born at gestations of 23 to 33 weeks. Reduced growth of the
      corpus callosum in weeks 2 to 6, places these infants at elevated risks of later
      psychomotor delay and cerebral palsy.

PMID- 16950987
TI  - The impact of early childhood lead exposure on brain organization: a functional
      magnetic resonance imaging study of language function.
AB  - OBJECTIVES: The purpose of this work was to assess the long-term impact of
      childhood lead exposure on the neurosubstrate of language function and brain
      organization. METHODS: Young adults from the Cincinnati Lead Study were recruited
      to undergo functional magnetic resonance image scanning while performing a verb
      generation task. These subjects have been followed from birth through early
      childhood with extensive documentation of lead exposure, neuropsychology, and
      behavior. Forty-two subjects provided useful imaging data. The locale, strength,
      and the correlation between brain language activation and childhood blood lead
      concentration were studied. RESULTS: After adjusting for potential confounders,
      the activation in left frontal cortex, adjacent to Broca's area, and left middle
      temporal gyrus, including Wernicke's area, were found to be significantly
      associated with diminished activation in subjects with higher mean childhood
      blood lead levels, whereas the compensatory activation in the right hemisphere
      homolog of Wernicke's area was enhanced in subjects with higher blood lead
      levels. CONCLUSION: This study indicates that childhood lead exposure has a
      significant and persistent impact on brain reorganization associated with
      language function.

PMID- 16950988
TI  - Long-term follow-up of Swedish children vaccinated with acellular pertussis
      vaccines at 3, 5, and 12 months of age indicates the need for a booster dose at 5
      to 7 years of age.
AB  - OBJECTIVES: The purpose of this work was to evaluate the long-term effectiveness
      of vaccination with acellular pertussis vaccines at 3, 5, and 12 months of age.
      METHODS: Clinical follow-up of reported culture- and polymerase chain reaction
      confirmed cases of pertussis was initiated during October 1997 in most of Sweden
      (except Gothenburg and environs). The study population included 90% of Swedish
      children born during 1996 or later (ie, who received diphtheria-tetanus-acellular
      pertussis vaccines at 3, 5, and 12 months of age) and children who had
      participated in a large pertussis vaccine trial in 1993-1996. Age-specific
      incidences were estimated using reported culture- or polymerase chain reaction
      confirmed pertussis from October 1997 to September 2004 in areas covered by
      enhanced surveillance. In addition, annual overall and age-specific incidences of
      pertussis throughout Sweden before and after introduction of acellular pertussis
      vaccines were estimated. RESULTS: The overall incidence of notified culture- and
      polymerase chain reaction-confirmed pertussis dropped from 113 to 150 per 100,000
      during 1992-1995 to 11 to 16 per 100,000 during 2001-2004. In areas of enhanced
      surveillance, the incidence of pertussis was 31 per 100,000 person-years after 2
      doses and 19 per 100,000 person-years after the third dose at 12 months of age.
      The age-specific incidence remained low for approximately 5 years after the third
      dose but increased in children aged 6 to 8 years, becoming 32 and 48 per 100,000
      person-years, respectively. The highest incidence occurred among infants who were
      unvaccinated or had received only 1 dose of diphtheria-tetanus-acellular
      pertussis vaccine. CONCLUSIONS: The increased incidence among 7- to 8-year-olds
      (ie, mainly acellular pertussis vaccine-vaccinated children) suggests waning of
      vaccine-induced protection from pertussis. Along with a concomitant increase in
      incidence among infants, most likely infected by older siblings, these data
      suggest a booster dose of acellular pertussis vaccine is warranted from 5 to 7
      years of age.

PMID- 16950986
TI  - A functional magnetic resonance imaging study of the long-term influences of
      early indomethacin exposure on language processing in the brains of prematurely
      born children.
AB  - BACKGROUND: Previous studies have demonstrated that indomethacin lowers the
      incidence and decreases the severity of intraventricular hemorrhage, as well as
      improves the cognitive outcome, in prematurely born male infants. OBJECTIVE: The
      purpose of this work was to use functional magnetic resonance imaging to test the
      hypothesis that neonatal indomethacin treatment would differentially affect brain
      activation across genders in school-aged, prematurely born children during
      performance of a language task. METHODS: Forty-seven prematurely born children
      (600-1250-g birth weight) and 24 matched term control subjects were evaluated
      using a functional magnetic resonance imaging passive language task and
      neurodevelopmental assessments that included the Wechsler Intelligence Scale for
      Children-III and the Peabody Picture Vocabulary Test-Revised. Neural activity was
      assessed during both phonologic and semantic processing in the functional
      magnetic resonance imaging protocol. RESULTS: Neurodevelopmental assessments
      demonstrated significant differences in full-scale, verbal, and performance
      intelligence quotient, as well as Peabody Picture Vocabulary Test scores, between
      the preterm and term control subjects. Rates of perinatal complications did not
      differ significantly across preterm treatment groups, but male preterm subjects
      randomly assigned to saline tended to have lower Peabody Picture Vocabulary Test
      Revised scores than did all of the other preterm groups. During phonological
      processing, a significant treatment-by-gender effect was demonstrated in 3 brain
      regions: the left inferior parietal lobule, the left inferior frontal gyrus
      (Broca's area), and the right dorsolateral prefrontal cortex. CONCLUSIONS: These
      data demonstrate a differential effect of indomethacin administration early in
      postnatal life on the subsequent development of neural systems that subserve
      language functioning in these male and female preterm infants.

PMID- 16950989
TI  - Simultaneous multigene mutation detection in patients with sensorineural hearing
      loss through a novel diagnostic microarray: a new approach for newborn screening
      follow-up.
AB  - OBJECTIVE: The advent of universal newborn hearing screening in the United States
      and other countries, together with the identification of genes involved in the
      process of hearing, have led to an increase in both the need and opportunity for
      accurate molecular diagnosis of patients with hearing loss. Deafness and hearing
      impairment have a genetic cause in at least half the cases. The molecular genetic
      basis for the majority of these patients remains obscure, however, because of the
      absence of associated clinical features in approximately 70% (ie, nonsyndromic
      hearing loss) of patients, genetic heterogeneity, and the lack of molecular
      genetic tests that can evaluate a large number of mutations across multiple
      genes. DESIGN: We report on the development of a diagnostic panel with 198
      mutations underlying sensorineural (mostly nonsyndromic) hearing loss. This
      panel, developed on a microarray, is capable of simultaneous evaluation of
      multiple mutations in 8 genes (GJB2, GJB6, GJB3, GJA1, SLC26A4, SLC26A5 and the
      mitochondrial genes encoding 12S rRNA and tRNA-Ser[UCN]). RESULTS: The arrayed
      primer extension array for sensorineural hearing loss is based on a versatile
      platform technology and is a robust, cost-effective, and easily modifiable assay.
      Because hearing loss is a major public health concern and common at all ages,
      this test is suitable for follow-up after newborn hearing screening and for the
      detection of a genetic etiology in older children and adults. CONCLUSIONS:
      Comprehensive and relatively inexpensive genetic testing for sensorineural
      hearing loss will improve medical management for affected individuals and genetic
      counseling for their families.

PMID- 16950990
TI  - Effect of hospital characteristics on outcomes from pediatric cardiopulmonary
      resuscitation: a report from the national registry of cardiopulmonary
      resuscitation.
AB  - OBJECTIVE: Cardiac arrest is uncommon among pediatric patients. Prehospital data
      demonstrate differences in care processes between children and adults receiving
      cardiopulmonary resuscitation and advanced life support. We sought to evaluate
      whether children receiving in-hospital cardiopulmonary resuscitation would attain
      superior 24-hour survival in hospitals with a higher level of pediatric physician
      staffing, greater intensity of pediatric care services, and higher pediatric
      patient volume. METHODS: A retrospective cohort of 778 hospital inpatients aged <
      18 years receiving cardiopulmonary resuscitation was identified from the National
      Registry of Cardiopulmonary Resuscitation from January 2000 to December 2002.
      Data on hospital pediatric facilities were obtained via telephone survey.
      Univariate analyses comparing 24-hour survivors and nonsurvivors were conducted
      using Wilcoxon rank-sum testing for continuous variables and chi2 analysis for
      dichotomous variables. Multivariate regression analysis was done to examine
      hospital characteristics as independent predictors of 24-hour survival. RESULTS:
      Complete data were available for 677 patients. Univariate analyses showed an
      association between several pediatric-specific facility characteristics and 24
      hour survival. After accounting for indicators of pre-event clinical condition
      and monitoring, multivariate analysis showed improved 24-hour survival in
      hospitals staffed by pediatric residents and surgeons and pediatric residents,
      surgeons, and fellows than for hospitals with no pediatric physician staffing or
      pediatric surgeons alone. Measures of available facilities and patient volume
      were not associated with improved outcome. CONCLUSIONS: Improved 24-hour survival
      for children receiving in-hospital cardiopulmonary resuscitation is associated
      with the presence of pediatric residents and fellows.

PMID- 16950991
TI  - Screening for posttraumatic stress disorder in children after accidental injury.
AB  - OBJECTIVE: Children who have experienced an accidental injury are at increased
      risk of developing posttraumatic stress disorder. It is, therefore, essential
      that strategies are developed to aid in the early identification of children at
      risk of developing posttraumatic stress disorder symptomatology after an
      accident. The aim of this study was to examine the ability of the Child Trauma
      Screening Questionnaire to predict children at risk of developing distressing
      posttraumatic stress disorder symptoms 1 and 6 months after a traumatic accident.
      METHODS: Participants were 135 children (84 boys and 51 girls; with their
      parents) who were admitted to the hospital after a variety of accidents,
      including car- and bike-related accidents, falls, burns, dog attacks, and
      sporting injuries. The children completed the Child Trauma Screening
      Questionnaire and the Children's Impact of Events Scale within 2 weeks of the
      accident, and the Anxiety Disorders Interview Schedule for Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition, Child Version, was
      conducted with the parents to assess full and subsyndromal posttraumatic stress
      disorder in their child 1 and 6 months after the accident. RESULTS: Analyses of
      the results revealed that the Child Trauma Screening Questionnaire correctly
      identified 82% of children who demonstrated distressing posttraumatic stress
      disorder symptoms (9% of sample) 6 months after the accident. The Child Trauma
      Screening Questionnaire was also able to correctly screen out 74% of children who
      did not demonstrate such symptoms. Furthermore, the Child Trauma Screening
      Questionnaire outperformed the Children's Impact of Events Scale. CONCLUSIONS:
      The Child Trauma Screening Questionnaire is a quick, cost-effective and valid
      self-report screening instrument that could be incorporated in a hospital setting
      to aid in the prevention of childhood posttraumatic stress disorder after
      accidental trauma.

PMID- 16950992
TI  - Growth and health in children with moderate-to-severe cerebral palsy.
AB  - BACKGROUND: Children with cerebral palsy frequently grow poorly. The purpose of
      this study was to describe observed growth patterns and their relationship to
      health and social participation in a representative sample of children with
      moderate-severe cerebral palsy. METHODS: In a 6-site, multicentered, region-based
      cross-sectional study, multiple sources were used to identify children with
      moderate or severe cerebral palsy. There were 273 children enrolled, 58% male,
      71% white, with Gross Motor Function Classification System levels III (22%), IV
      (25%), or V (53%). Anthropometric measures included: weight, knee height, upper
      arm length, midupper arm muscle area, triceps skinfold, and subscapular skinfold.
      Intraobserver and interobserver reliability was established. Health care use
      (days in bed, days in hospital, and visits to doctor or emergency department) and
      social participation (days missed of school or of usual activities for child and
      family) over the preceding 4 weeks were measured by questionnaire. Growth curves
      were developed and z scores calculated for each of the 6 measures. Cluster
      analysis methodology was then used to create 3 distinct groups of subjects based
      on average z scores across the 6 measures chosen to provide an overview of
      growth. RESULTS: Gender-specific growth curves with 10th, 25th, 50th, 75th, and
      90th percentiles for each of the 6 measurements were created. Cluster analyses
      identified 3 clusters of subjects based on their average z scores for these
      measures. The subjects with the best growth had fewest days of health care use
      and fewest days of social participation missed, and the subjects with the worst
      growth had the most days of health care use and most days of participation
      missed. CONCLUSIONS: Growth patterns in children with cerebral palsy were
      associated with their overall health and social participation. The role of these
      cerebral palsy-specific growth curves in clinical decision-making will require
      further study.

PMID- 16950993
TI  - Single kidney and sports participation: perception versus reality.
AB  - OBJECTIVES: Physician opinions and practice patterns regarding the participation
      of children and adolescents with single, normal kidneys in contact/collision
      sports are widely varied. We hypothesize that limitation of participation from
      play based only on the presence of a single kidney is not supported by available
      data. We sought to determine recommendations of pediatric nephrologists regarding
      the participation of patients with single, normal kidneys in contact/collision
      sports and review the literature to determine the rate of sports-related kidney
      injury compared with other organs. METHODS: Members of the American Society of
      Pediatric Nephrology were surveyed regarding their recommendations for
      participation of patients with single, normal kidneys in contact/collision
      sports. Medical and sports literature databases were searched to determine sports
      related kidney, brain, spinal cord, and cardiac injury rates and the sports
      associated with kidney injury. RESULTS: Sixty-two percent of respondents would
      not allow contact/collision sports participation. Eighty-six percent of
      respondents barred participation in American football, whereas only 5% barred
      cycling. Most cited traumatic loss of function as the reason for discouraging
      participation. The literature search found an incidence of catastrophic sports
      related kidney injury of 0.4 per 1 million children per year from all sports.
      Cycling was the most common cause of sports-related kidney injury causing > 3
      times the kidney injuries as football. American football alone accounted for 0.9
      to 5.3 fatal brain injuries and 4.9 to 7.3 irreversible spinal cord injuries per
      1 million players per year. Commotio cordis causes 2.1 to 9.2 deaths per year.
      CONCLUSIONS: Most pediatric nephrologists prohibit contact/collision sports
      participation by athletes with a single kidney, particularly football. The
      available evidence suggests that cycling is far more likely to cause kidney
      injury. In addition, kidney injury from sports is much less common than
      catastrophic brain, spinal cord, or cardiac injury. Restricting participation of
      patients with a single, normal kidney from contact/collision sports is
      unwarranted.

PMID- 16950994
TI  - Use and efficacy of endotracheal versus intravenous epinephrine during neonatal
      cardiopulmonary resuscitation in the delivery room.
AB  - OBJECTIVE: Given the paucity of information regarding endotracheal epinephrine
      for newborn resuscitation, the objectives of this study were: (1) to determine
      the frequency of endotracheal epinephrine use in newborns in the delivery room,
      and (2) to determine whether the previously recommended dose of 0.01 to 0.03
      mg/kg of endotracheal epinephrine is effective in establishing a return of
      spontaneous circulation. PATIENTS AND METHODS: A retrospective review was
      conducted for all neonates who received > or = 1 dose of epinephrine in the
      delivery room between January 1999 and December 2004. Infants who received > or =
      1 dose of endotracheal epinephrine in the delivery room during resuscitation were
      included in the study population whether or not they survived to be admitted to
      the NICU. Exclusion criteria included lethal congenital anomalies, delivery
      outside the hospital, and missing medical charts. RESULTS: Of 93,656 infants, 52
      neonates (0.06%) received epinephrine in the delivery room, 5 of whom met
      exclusion criteria. Of the remaining 47 infants, 44 (94%) received the first dose
      via the endotracheal tube. Only 14 (32%) of 44 achieved return of spontaneous
      circulation after endotracheal tube administration of epinephrine. Of the 30
      remaining infants, 23 (77%) had return of spontaneous circulation with
      intravenous epinephrine after initially failing endotracheal tube epinephrine.
      There were no differences in clinical characteristics between newborns who
      responded to endotracheal tube versus intravenous epinephrine except for a lower
      blood glucose on NICU admission (52 vs 113 mg%). CONCLUSIONS: Endotracheal
      epinephrine is frequently used when intensive resuscitation is required in the
      delivery room. The previously recommended endotracheal epinephrine dose of 0.01
      to 0.03 mg/kg is often ineffective. Higher endotracheal doses will likely be
      needed to improve efficacy. A prospective study is needed to determine the best
      endotracheal epinephrine dosing regimen. Until such information is available,
      intravenous administration should be the preferred route of delivery.

PMID- 16950995
TI  - Stiffness of systemic arteries in appropriate- and small-for-gestational-age
      newborn infants.
AB  - OBJECTIVE: The purpose of this work was to study the stiffness of systemic
      arteries in appropriate and small for gestational age newborn infants. The
      distance between diametrically opposite points of the arterial lumen was measured
      with a phase locked loop echo tracking system coupled to a B-mode ultrasonic
      imager. PATIENTS AND METHODS: A cross-sectional study of 51 appropriate for
      gestation age infants including 22 preterm infants was done to obtain normal
      data. We also studied 47 small for gestational age infants, who were identified
      antenatally by an umbilical artery Doppler flow waveform pulsatility index > 95th
      percentile. The stiffness index of the common carotid artery and abdominal aorta
      was calculated from the relationship between systemic blood pressure and arterial
      diameter during the cardiac cycle. RESULTS: In the appropriate for gestation age
      group, the systolic and diastolic diameters of the common carotid artery and
      abdominal aorta, as well as the stiffness index, increased with the gestational
      age at birth. In the small for gestational age group, the arterial diameters and
      blood pressure were also within the reference range. Using the arterial stiffness
      index values from the appropriate for gestation age group, the small for
      gestational age group was divided into 3 subgroups: 18 infants with normal
      stiffness index values for both arteries, 19 infants with a high stiffness index
      of the abdominal aorta, and 10 infants with a high stiffness index for both
      arteries. The clinical outcome was significantly worse in the latter 2 subgroups
      compared with the normal infants and was also worse in the infants with a high
      stiffness index for both arteries compared with the high abdominal aorta
      subgroup. CONCLUSION: The antenatal increase of afterload caused by a high
      placental vascular resistance was associated with a decrease of aortic
      distensibility in the compromised small for gestational age infants, suggesting
      that the structure of the aortic wall was altered. In the most profoundly
      compromised small for gestational age infants, the high stiffness index of both
      the common carotid artery and abdominal aorta may indicate more extensive
      arterial damage.

PMID- 16950996
TI  - Asthma symptom burden: relationship to asthma severity and anxiety and depression
      symptoms.
AB  - OBJECTIVE: The purpose of this work was to examine the relationship between youth
      reported asthma symptoms, presence of anxiety or depressive disorders, and
      objective measures of asthma severity among a population-based sample of youth
      with asthma. METHODS: We conducted a telephone survey of 767 youth with asthma
      (aged 11-17 years) enrolled in a staff model health maintenance organization. The
      Diagnostic Interview Schedule for Children was used to diagnose Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition, anxiety and depressive
      disorders; the Child Health Status-Asthma questionnaire (modified) was used to
      assess asthma symptoms; and automated administrative data were used to measure
      asthma treatment intensity and severity. Analyses of covariance were performed to
      determine whether the number of anxiety and depressive symptoms was related to
      the number of asthma symptoms. Logistic regression analyses were used to evaluate
      the strength of association between individual symptoms of asthma and the
      presence of an anxiety or depressive disorder and objective measures of asthma
      severity. RESULTS: After adjusting for demographic characteristics, objective
      measures of asthma severity, medical comorbidity, and asthma treatment intensity,
      youth with > or = 1 anxiety or depressive disorder (N = 125) reported
      significantly more days of asthma symptoms over the previous 2 weeks than youth
      with no anxiety or depressive disorders. The overall number of reported asthma
      symptoms was significantly associated with the number of anxiety and depressive
      symptoms endorsed by youth. In logistic regression analyses, having an anxiety or
      depressive disorder was also strongly associated with each of the 6 asthma
      specific symptoms, as well as the 5 related nonspecific somatic symptoms
      contained in the Child Health Status-Asthma questionnaire. CONCLUSIONS: The
      presence of an anxiety or depressive disorder is highly associated with increased
      asthma symptom burden for youth with asthma.

PMID- 16950997
TI  - Electrocardiography in the diagnosis of right ventricular hypertrophy in
      children.
AB  - OBJECTIVE: Although the electrocardiogram is commonly obtained in the evaluation
      of patients with pulmonary hypertension, its value as a screening test for right
      ventricular hypertrophy or pulmonary hypertension is unclear. Therefore, we
      sought to determine the value of an electrocardiogram in the diagnosis of right
      ventricular hypertrophy using echocardiography as the gold standard. METHODS: We
      identified children without congenital heart disease who underwent evaluation for
      suspected pulmonary hypertension that included both an electrocardiogram and
      echocardiography within a specified time frame. RESULTS: A total of 76
      echocardiography-electrocardiogram pairs for pulmonary hypertension were
      identified. Although there was a significant relationship between
      electrocardiogram and echocardiography evidence of right ventricular hypertrophy,
      the sensitivity of an electrocardiogram in diagnosing echocardiography-documented
      right ventricular hypertrophy was only 69%, and the positive predictive value was
      67%. There was no relationship between electrocardiogram changes and Doppler
      tricuspid regurgitation gradient. CONCLUSION: Despite a statistically significant
      relationship between an electrocardiogram and echocardiography in the diagnosis
      of right ventricular hypertrophy, an electrocardiogram has limited value as a
      screening tool for right ventricular hypertrophy because of its relatively low
      sensitivity and positive predictive value.

PMID- 16950998
TI  - Pulmonary nitric oxide synthases and nitrotyrosine: findings during lung
      development and in chronic lung disease of prematurity.
AB  - BACKGROUND: Nitric oxide mediates and modulates pulmonary transition from fetal
      to postnatal life. NO is synthesized by 3 nitric oxide synthase isoforms. One key
      pathway of nitric oxide metabolism results in nitrotyrosine, a stable, measurable
      marker of nitric oxide production. OBJECTIVE: The purpose of this study was to
      assess, by semiquantitative immunohistochemistry, nitric oxide synthase isoforms
      and nitrotyrosine at different airway and vascular tree levels in the lungs of
      neonates at different gestational ages and to compare results in control groups
      to those in infants with chronic lung disease. DESIGN/METHODS: Formalin-fixed,
      paraffin-embedded, postmortem lung blocks were prepared for immunohistochemistry
      using antibodies to each nitric oxide synthase isoform and to nitrotyrosine.
      Blinded observers evaluated the airway and vascular trees for staining intensity
      (0-3 scale) at 5 levels and 3 levels, respectively. The control population
      consisted of infants from 22 to 42 weeks' gestation who died in < 48 hours.
      Results were compared with gestation-matched infants with varying severity of
      chronic lung disease. RESULTS: In control and chronic lung disease groups, 22 to
      42 weeks' gestation, staining for all 3 of the nitric oxide synthase isoforms was
      found in the airway epithelium from the bronchus to the alveolus or distal-most
      airspace. The abundance or distribution of nitric oxide synthase-3 staining in
      the airways did not show significant correlation with gestational age or severity
      of chronic lung disease. In the vascular tree, intense nitric oxide synthase-3
      and moderate nitric oxide synthase-2 staining was found; nitric oxide synthase-1
      was not consistently stained. Nitrotyrosine did stain in the pulmonary tree.
      Compared with controls where nitrotyrosine staining was minimal, regardless of
      gestation, in infants with chronic lung disease there was more than fourfold
      increase between severe chronic lung disease (n = 12) and either mild chronic
      lung disease or control infants (n = 16). CONCLUSIONS: All 3 of the nitric oxide
      synthase isoforms and nitrotyrosine are detectable by immunohistochemistry early
      in lung development. Nitric oxide synthase ontogeny shows no significant changes
      in abundance or distribution with advancing gestational age nor with chronic lung
      disease. Nitrotyrosine is significantly increased in severe chronic lung disease.

PMID- 16950999
TI  - Neonatal screening for very long-chain acyl-coA dehydrogenase deficiency:
      enzymatic and molecular evaluation of neonates with elevated C14:1-carnitine
      levels.
AB  - OBJECTIVE: Neonatal screening programs for very long-chain acyl-coenzyme A
      dehydrogenase deficiency have been implemented recently in various countries.
      Mildly elevated C14:1-carnitine on day 3 of life strongly suggests very long
      chain acyl-coenzyme A dehydrogenase deficiency. DESIGN: We characterized 11
      neonates with elevated C14:1-carnitine by enzyme and molecular analyses.
      Palmitoyl-coenzyme A oxidation was measured in lymphocytes. Sequencing of all 20
      exons of the VLCAD gene was performed from genomic DNA. RESULTS: Palmitoyl
      coenzyme A oxidation revealed significantly decreased residual activities
      consistent with very long-chain acyl-coenzyme A dehydrogenase deficiency in 7
      neonates. In 2 individuals, residual activities of 48% and 44%, respectively,
      suggested heterozygosity. Two disease-causing mutations were detected in 6 of 7
      neonates with very long-chain acyl-coenzyme A dehydrogenase deficiency; in the
      remaining 1 patient, only 1 mutation was identified. Of 2 individuals with
      residual activities consistent with heterozygosity, 1 was heterozygous for a
      VLCAD mutation. The other child and both individuals with normal palmitoyl
      coenzyme A oxidation had normal genotypes. CONCLUSIONS: In 4 of 11 neonates
      identified with elevated C14:1-carnitine, very long-chain acyl-coenzyme A
      dehydrogenase deficiency was excluded. A C14:1-carnitine level > 1 micromol/L
      strongly suggests very long-chain acyl-coenzyme A dehydrogenase deficiency,
      whereas concentrations < or = 1 micromol/L do not allow a clear discrimination
      among affected patients, carriers, and healthy individuals. Further diagnostic
      evaluation, including enzyme and molecular analyses, is essential to identify
      very long-chain acyl-coenzyme A dehydrogenase deficiency correctly.

PMID- 16951000
TI  - Pretransport and posttransport characteristics and outcomes of neonates who were
      admitted to a cardiac intensive care unit.
AB  - OBJECTIVE: The objective for this study was to characterize the impact and the
      safety of transporting neonates with known or suspected cardiac abnormalities.
      METHODS: We reviewed retrospectively the charts and computerized records of 192
      admissions to a cardiac ICU in 2002. Patients were included when they were < 28
      days of age at admission and were transported from adjacent obstetric facilities
      (local N = 70) or other inpatient medical facilities (transport N = 122).
      Demographic, clinical, pharmacologic, laboratory, and diagnostic information was
      obtained before transport (when available) and within 3 hours of arrival. Arrival
      status was considered optimal when measured metabolic and clinical parameters all
      were within range. Outcome variables included days on ventilator, days in ICU,
      days in hospital, and death. RESULTS: Of local admissions, 31 (44%) patients had
      61 suboptimal arrival values, including pH < 7.25 (n = 11), saturation < 70% (n =
      12), and temperature < 36 degrees C (n = 9). There were 69 undocumented values in
      39 patients. Of transported patients, 55 (45%) had 86 suboptimal arrival values,
      including pH < 7.25 (n = 8), saturation < 70% (n = 14), and temperature < 36
      degrees C (n = 13). There were 98 undocumented values in 53 patients. No in
      transport deaths or catastrophic events occurred. Local admissions were more
      likely to have a prenatal diagnosis of heart disease and had more complex disease
      and higher mortality. Other outcome parameters were not significantly different
      between the 2 groups. Low admission arterial saturation, pH, and core temperature
      were not correlated with adverse outcome measures. CONCLUSIONS: Although we did
      not encounter major transport complications, opportunities exist to optimize
      arrival status and improve surveillance and documentation.

PMID- 16951001
TI  - Impact of prenatal and/or postnatal growth problems in low birth weight preterm
      infants on school-age outcomes: an 8-year longitudinal evaluation.
AB  - OBJECTIVE: The objective of this study was to assess the 8-year growth,
      cognitive, behavioral status, health status, and academic achievement in low
      birth weight preterm infants who had failure to thrive only, were small for
      gestational age only, had failure to thrive plus were small for gestational age,
      or had normal growth. METHODS: A total of 985 infants received standardized
      evaluations to age 8; 180 infants met the criteria for failure to thrive between
      4 and 36 months' gestational corrected age. The following outcome variables were
      collected at age 8: growth, cognitive, behavioral status, health status, and
      academic achievement. Multivariate analyses were performed among the 4 growth
      groups on all 8-year outcome variables. RESULTS: Children who both were small for
      gestational age and had failure to thrive were the smallest in all growth
      variables at age 8, and they also demonstrated the lowest cognitive and academic
      achievement scores. The children with failure to thrive only were significantly
      smaller than the children with normal growth in all growth variables and had
      significantly lower IQ scores. Those who were small for gestational age only did
      not differ from those with normal growth in any cognitive or academic achievement
      measures. There were no differences among the 4 groups in behavioral status or
      general health status. CONCLUSION: Low birth weight preterm infants who develop
      postnatal growth problems, particularly when associated with prenatal growth
      problems, demonstrate lower physical size, cognitive scores, and academic
      achievement at age 8. There does not seem to be an independent affect of small
      for gestational age status on 8-year cognitive status and academic achievement
      when postnatal growth is adequate.

PMID- 16951002
TI  - Incidence and nature of adverse events during pediatric sedation/anesthesia for
      procedures outside the operating room: report from the Pediatric Sedation
      Research Consortium.
AB  - OBJECTIVE: We sought to use a large database of prospectively collected data on
      pediatric sedation and/or anesthesia for diagnostic and therapeutic procedures to
      delineate the nature and the frequency of adverse events that are associated with
      sedation/anesthesia care for procedures that are performed outside the operating
      room in children. METHODS: Data were collected by the Pediatric Sedation Research
      Consortium, a collaborative group of 35 institutions that are dedicated to
      improving sedation/anesthesia care for children internationally. Members
      prospectively enrolled consecutive patients who were receiving sedation or
      anesthesia for procedures. Data on demographics, primary illness, coexisting
      illness, procedure performed, medications used, outcomes, airway interventions,
      and adverse events were collected and reported on a Web-based data collection
      tool. RESULTS: A total of 26 institutions submitted data on 30,037
      sedation/anesthesia encounters during the study period from July 1, 2004, to
      November 15, 2005. Serious adverse events were rare in the institutions involved
      in this study; there were no deaths. Cardiopulmonary resuscitation was required
      once. Less serious events were more common with O2 desaturation below 90% for >
      30 seconds, occurring 157 times per 10000 sedations. Stridor and laryngospasm
      both occurred in 4.3 per 10,000 sedations. Unexpected apnea, excessive
      secretions, and vomiting had frequencies of 24, 41.6, and 47.2 per 10,000
      encounters, respectively. CONCLUSIONS: Our data indicate that pediatric
      sedation/anesthesia for procedures outside the operating room is unlikely to
      yield serious adverse outcomes in a collection of institutions with highly
      motivated and organized sedation services. However, the safety of this practice
      depends on the systems' ability to manage less serious events.

PMID- 16951003
TI  - Rural and urban children with asthma: are school health services meeting their
      needs?
AB  - OBJECTIVE: Children with asthma spend a large portion of their day in school, and
      the extent to which public schools are prepared to meet their health needs is an
      important issue. The objective of this study was to identify asthma policies and
      practices in rural and urban school settings and to compare them with current
      National Heart, Lung, and Blood Institute recommendations. METHODS: A stratified
      random sample of school nurses who represented each of the 500 active
      Pennsylvania school districts were surveyed in 2004 concerning nurse staffing
      patterns, availability of asthma monitoring and treatment-related equipment,
      emergency preparedness, availability of asthma-related support and case
      management services, school-specific procedures including identification of
      children with asthma and accessibility of inhaler medication during school hours,
      presence and content of written asthma management plans, and perceived obstacles
      to asthma management in the school setting. Sampling weights were incorporated
      into the analyses to take the survey design into account. RESULTS: The overall
      response rate was 76%, with a total of 757 surveys analyzed. In more than half of
      secondary schools and three quarters of elementary schools, nurses were present <
      40 hours per week. Nearly 1 in 5 schools reported that staff who know what to do
      for a severe asthma attack were not always available. In 72% of rural schools,
      children were allowed to self-carry rescue inhalers, as compared with 47% of
      urban schools. Asthma management plans were on file for only 1 quarter of
      children with asthma, and important information often was omitted. Approximately
      half of the schools were equipped with peak flow meters and nebulizers, and
      spacers were available in 1 third of schools. CONCLUSIONS: Improvements are
      needed to bring schools into compliance with current recommendations, including
      more consistent availability of knowledgeable staff, improved access to asthma
      monitoring and treatment-related equipment, more universal use of asthma
      management plans, and greater access to inhalers while at school, including
      increasing the proportion of children who are allowed to carry and self
      administer inhaler medication.

PMID- 16951004
TI  - Comparing perceptions of training for medicine-pediatrics and categorically
      trained physicians.
AB  - OBJECTIVE: The objective of this study was to compare the perceptions of clinical
      preparedness among graduates of categorical pediatric and internal medicine
      residency programs versus medicine-pediatric training programs and whether these
      varied for recent or older graduates. METHODS: A mail survey study was conducted
      in the fall of 2004 of a random sample of 245 and 246 internal medicine
      physicians who applied for or took a general certifying examination between 1980
      and 1997 (older graduates) and between 1998 and 2003 (recent graduates),
      respectively, and a random sample of 248 and 247 pediatricians who applied for or
      took a general certifying examination between 1980 and 1997 (older graduates) and
      between 1998 and 2003 (recent graduates). Analyses compared results from a
      recent, similar survey of medicine-pediatric physicians. RESULTS: Response rate
      for pediatricians was 78% and for internal medicine physicians was 64%.
      Categorically trained pediatricians were more likely than medicine-pediatrics
      trained physicians to report that they were very well prepared to care for
      infants (65% vs 50%) but less likely well trained to care for adolescents (17% vs
      45%). Categorically trained internal medicine residents were less likely to feel
      very well prepared to care for both adults and elders than their medicine
      pediatrics-trained counterparts. CONCLUSIONS: Categorically trained pediatricians
      and internal medicine physicians believed that they were no better prepared to
      care for their patients than medicine-pediatrics-trained physicians. Regardless
      of their beliefs of their preparedness, medicine-pediatrics physicians in
      practice spend a significant majority of their time in the care of adults rather
      than children. Our findings indicate that this is not because of their perception
      of a lack of training or preparation in the care of children relative to
      categorically trained pediatricians. Other factors, including but not limited to
      patient demographic changes, reimbursement for care, and the job market,
      potentially play a significant role.

PMID- 16951005
TI  - Pheochromocytoma and paraganglioma in children: a review of medical and surgical
      management at a tertiary care center.
AB  - OBJECTIVE: The aim of this study was to review our institutional experience
      managing pheochromocytomas and paragangliomas in children. METHODS: A
      retrospective chart review of the Mayo Clinic database from 1975 to 2005
      identified 30 patients < 18 years of age with histologically confirmed
      pheochromocytoma or paraganglioma. RESULTS: There were 12 patients with
      pheochromocytomas and 18 with paragangliomas. The most common presenting symptoms
      were hypertension (64%), palpitation (53%), headache (47%), and mass-related
      effects (30%). Nine patients (30%) had a genetic mutation or documented family
      history of pheochromocytoma or paraganglioma. Fourteen patients (47%) had
      malignant disease, whereas 16 (53%) had benign disease. Logistic analysis showed
      that statistically significant risk factors for malignancy were (1)
      paraganglioma, (2) apparently sporadic, as opposed to familial, pheochromocytoma
      or paraganglioma, and (3) tumor size of > 6 cm. Surgical resection was performed
      for 28 patients (93%), with perioperative mortality and major morbidity rates of
      0% and 10%, respectively. Resection achieved symptomatic relief for 25 patients
      (83%). All patients with benign disease appeared cured after resection. For
      patients with malignant disease, the 5- and 10-year disease-specific survival
      rates were 78% and 31%, respectively, and the mean survival time was 157 +/- 32
      months. CONCLUSIONS: The incidence of malignant pheochromocytoma/paraganglioma
      was high in children (47%), particularly those with apparently sporadic disease,
      paraganglioma, and tumor diameters of > 6 cm. Patients with a known genetic
      mutation or familial pheochromocytoma/paraganglioma were more likely to achieve
      resection with negative microscopic margins and had improved disease-specific
      mortality rates. Surgical resection remains the treatment of choice for
      pheochromocytoma and paraganglioma.

PMID- 16951006
TI  - Little evidence for early programming of weight and insulin resistance for
      contemporary children: EarlyBird Diabetes Study report 19.
AB  - OBJECTIVE: The aim of this study was to evaluate whether adaptive responses made
      to the uterine or very early infant environment are affecting the current
      metabolic health of young children in the United Kingdom. METHODS: Participants
      were 300 healthy children and their parents from the EarlyBird Diabetes Study
      cohort. Children were recruited from randomly selected schools at 5 years of age.
      Retrospective measures were maternal prepregnancy weight (n = 230), maternal
      fasting glucose levels at 28 weeks of pregnancy (n = 27), birth weight, and
      infant weight at ages 3 and 6 weeks. Prospective measures were insulin
      resistance, height, weight, and percentage of body fat (sum of 5 skinfold
      measurements) at ages 5, 6, 7, and 8 years. RESULTS: Maternal third-trimester
      fasting glucose levels were associated positively with birth weight but were not
      associated with either weight or insulin resistance for the same children at 8
      years. Birth weight was unrelated to insulin resistance at 8 years. There were no
      relationships between weight change in the first weeks of life and weight,
      percentage of fat, or insulin resistance at 8 years. Longer breastfeeding
      correlated inversely, although weakly, with percentage of body fat for boys only.
      Current weight was correlated with insulin resistance at 8 years. CONCLUSIONS:
      For these contemporary children, neither the gestational environment nor early
      postnatal growth predicted insulin resistance, which was best predicted by
      current weight. There was no evidence that predictive adaptive responses made by
      the fetus or infant affected the child's weight or insulin resistance later in
      childhood.

PMID- 16951007
TI  - Associations between sleep problems, anxiety, and depression in twins at 8 years
      of age.
AB  - OBJECTIVES: Associations between sleep and internalizing problems are complex and
      poorly understood. To better understand these covarying difficulties, genetic and
      environmental influences were estimated by using a twin design. METHODS: Three
      hundred 8-year-old twin pairs reported on their anxiety and depression by
      completing the Screen for Childhood Anxiety Related Emotional Disorders and the
      Children's Depression Inventory. Parents reported on their children's sleep
      problems by completing the Child Sleep Habits Questionnaire. RESULTS: Children
      reported by their parents to have different types of sleep problems self-reported
      more depression symptoms than those without. The correlation between total sleep
      problem score and depression was moderate. That between sleep problems and
      anxiety was smaller and was not examined further. The association between sleep
      problems and depression was mainly explained by genes, and there was substantial
      overlap between the genes influencing sleep problems and those influencing
      depression. There was smaller influence from environmental factors making family
      members alike, and environmental factors making family members different
      decreased the association between sleep problems and depression. CONCLUSIONS: A
      range of sleep difficulties are associated with depression in school-aged
      children, and the overall association between the 2 difficulties may be largely
      influenced by genes.

PMID- 16951008
TI  - Prognostic factors for early severity in a childhood multiple sclerosis cohort.
AB  - OBJECTIVE: The goal was to identify prognostic factors for an early severe course
      in a cohort of patients with childhood-onset multiple sclerosis, for the
      construction of a predictive tool. METHODS: The cohort consisted of 197 children
      from the French Kid Sclerose en Plaques neuropediatric cohort with
      relapsing/remitting multiple sclerosis beginning before the age of 16 years.
      Patients were included from 1990 to 2003. We used multivariate survival analysis
      (Cox model) to evaluate the prognostic value of clinical, MRI, and biological
      covariates at onset for the occurrence of a third attack or severe disability
      ("severity" outcome). RESULTS: The cohort was monitored for a mean of 5.5 +/- 3.6
      years. The "severity" outcome was recorded for 144 patients (73%). The risk of
      severity was higher for girls, for a time between the first and second attacks of
      < 1 year, for childhood-onset multiple sclerosis MRI criteria at onset, for an
      absence of severe mental state changes at onset, and for a progressive course. A
      derived childhood-onset multiple sclerosis potential index for early severity was
      found to have a positive predictive value for severity of > 35% for the upper 2
      quartiles. CONCLUSIONS: The clinical and MRI prognostic factors for early
      severity that were identified were used as the basis of a predictive tool, which
      will be validated in another cohort. This tool should make it possible to
      identify subgroups at risk of early severe disease and should facilitate
      therapeutic studies.

PMID- 16951009
TI  - Self-perceived health-related quality of life of former extremely low birth
      weight infants at young adulthood.
AB  - OBJECTIVES: The goals were to compare the self-reported, health-related quality
      of life of former extremely low birth weight and normal birth weight infants at
      young adulthood and to determine whether there were any changes over time.
      METHODS: A prospective, longitudinal, population-based study with concurrent
      control subjects was performed. We interviewed 143 of 166 extremely low birth
      weight survivors (birth weight: 501-1000 g; 1977-1982 births) and 130 of 145
      sociodemographically comparable, normal birth weight, reference subjects.
      Neurosensory impairments were present for 27% extremely low birth weight and 2%
      normal birth weight young adults. Health Utilities Index 2 was used to assess
      health status, and standard gamble technique was used to measure directly the
      self-reported, health-related, quality of life and 4 hypothetical health states.
      RESULTS: Extremely low birth weight young adults reported more functional
      limitations in cognition, sensation, mobility, and self-care, compared with
      control subjects. There were no differences between groups in the mean self
      reported, health-related, quality of life or between impaired (n = 38) and
      nonimpaired (n = 105) extremely low birth weight subjects. However, with a
      conservative approach of assigning a score of 0 for 10 severely disabled,
      extremely low birth weight subjects, the mean health-related quality of life was
      significantly lower than control values. Repeated-measures analysis of variance
      to compare health-related quality-of-life measurements obtained for young adults
      and teens showed the same decline in scores over time for both groups. There were
      no differences between groups in the ratings provided for the hypothetical health
      states. CONCLUSIONS: At young adulthood, health-related quality of life was not
      related to size at birth or to the presence of disability. There was a small
      decrease in health-related quality-of-life scores over time for both groups.

PMID- 16951010
TI  - The infant development, environment, and lifestyle study: effects of prenatal
      methamphetamine exposure, polydrug exposure, and poverty on intrauterine growth.
AB  - OBJECTIVE: Methamphetamine use among pregnant women is an increasing problem in
      the United States. Effects of methamphetamine use during pregnancy on fetal
      growth have not been reported in large, prospective studies. We examined the
      neonatal growth effects of prenatal methamphetamine exposure in the multicenter,
      longitudinal Infant Development, Environment and Lifestyle study. DESIGN/METHOD:
      The Infant Development, Environment and Lifestyle study screened 13808 subjects
      at 4 clinical centers: 1618 were eligible and consented, among which 84 were
      methamphetamine exposed, and 1534 were unexposed. Those who were methamphetamine
      exposed were identified by self-report and/or gas chromatography-mass
      spectrometry confirmation of amphetamine and metabolites in infant meconium.
      Those who were unexposed denied amphetamine use and had a negative meconium
      screen. Both groups included prenatal alcohol, tobacco, or marijuana use, but
      excluded use of opiates, LSD, PCP or cocaine only. Neonatal parameters included
      birth weight and gestational age in weeks. One-way analysis of variance and
      linear-regression analyses were conducted on birth weight by exposure. The
      relationship of methamphetamine exposure and the incidence of small for
      gestational age was analyzed using multivariate logistic-regression analyses.
      RESULTS: The methamphetamine exposed group was 3.5 times more likely to be small
      for gestational age than the unexposed group. Mothers who used tobacco during
      pregnancy were nearly 2 times more likely to have small-for-gestational-age
      infants. In addition, less maternal weight gain during pregnancy was more likely
      to result in a small-for-gestational-age infant. Birthweight in the
      methamphetamine exposed group was lower than the unexposed group. CONCLUSIONS:
      These findings suggest that prenatal methamphetamine use is associated with fetal
      growth restriction after adjusting for covariates. Continued follow-up will
      determine if these infants are at increased risk for growth abnormalities in the
      future.

PMID- 16951011
TI  - Improving pediatric prevention via the internet: a randomized, controlled trial.
AB  - BACKGROUND: Innovations to improve the delivery of pediatric preventive care are
      needed. METHODS: We enrolled children, 0 to 11 years of age, into a factorial,
      randomized, controlled trial of a tailored, evidence-based, Web site
      (MyHealthyChild) that provided information on prevention topics before a
      scheduled well-child visit. There were 2 components of the intervention, namely,
      parental Web content and provider notification. Parental Web content provided
      information to parents about prevention topics; provider notification
      communicated to physicians topics that were of interest to parents. We assigned
      887 children randomly to 4 groups (usual care, content only, content and
      notification, or notification only). Outcomes were determined with telephone
      follow-up surveys conducted 2 to 4 weeks after the visit. Poisson regression
      analysis was used to determine the independent effects of each intervention on
      the number of topics discussed and the number of preventive practices
      implemented. RESULTS: Parents in the notification/content group and in the
      notification-only group reported discussing more MyHealthyChild topics with their
      provider. Parents in the notification/content group and in the content-only group
      reported implementing more MyHealthyChild topic suggestions (such as use of a
      safety device). CONCLUSIONS: A Web-based intervention can activate parents to
      discuss prevention topics with their child's provider. Delivery of tailored
      content can promote preventive practices.

PMID- 16951012
TI  - Influenza vaccination coverage of children aged 6 to 23 months: the 2002-2003 and
      2003-2004 influenza seasons.
AB  - BACKGROUND: Beginning in 2002 the Advisory Committee on Immunization Practices
      encouraged, when feasible, annual influenza vaccination of all children aged 6 to
      23 months and household contacts and out-of-home caregivers of children < 2 years
      of age. OBJECTIVE: We sought to report influenza vaccination coverage for the
      2002-2003 and 2003-2004 influenza seasons among children aged 6 to 23 months
      according to demographic and immunization-provider characteristics. METHODS: Data
      from the 2003 and 2004 National Immunization Survey were analyzed. Two measures
      of childhood influenza vaccination are reported: receipt of > or = 1 influenza
      vaccination and full vaccination (ie, receipt of the appropriate number of doses
      on the basis of previous vaccination history). chi2 tests and logistic-regression
      analyses to test for associations between influenza vaccination status and
      demographic characteristics were performed. RESULTS: In the 2002-2003 and 2003
      2004 influenza seasons only 7.4% and 17.5%, respectively, of children aged 6 to
      23 months received > or = 1 influenza vaccination, whereas only 4.4% and 8.4%,
      respectively, were fully vaccinated. In both seasons, adjusted influenza
      vaccination coverage was significantly lower among children living below the
      poverty level; non-Hispanic black children; older children; children with less
      educated mothers; children vaccinated only at public clinics; and children not
      residing in a metropolitan statistical area. CONCLUSION: During the first 2 years
      of the Advisory Committee on Immunization Practices' encouragement for children
      aged 6 to 23 months to receive influenza vaccination, coverage was low, with
      significant demographic differences in receipt of vaccination. Beginning with the
      2004-2005 influenza season, they replaced the encouragement with a recommendation
      that children aged 6 to 23 months receive annual influenza vaccination.
      Substantial work remains to fully and equitably implement this new recommendation
      and ensure vaccination with 2 doses for previously unvaccinated children.

PMID- 16951013
TI  - Real-time continuous glucose monitoring in pediatric patients during and after
      cardiac surgery.
AB  - OBJECTIVES: Given the demonstrated benefit of euglycemia in critically ill
      patients as well as the risk for hypoglycemia during insulin infusion in
      children, we sought to validate a subcutaneous sensor for real-time continuous
      glucose monitoring in pediatric patients during and after cardiac surgery.
      METHODS: Children up to 36 months of age who were undergoing cardiac bypass
      surgery were recruited. After anesthetic induction, a continuous glucose
      monitoring system sensor (CGMS, Medtronic Minimed, Northridge, CA) was inserted
      subcutaneously. Sensors remained in place for up to 72 hours. Arterial blood
      glucose was measured intermittently in the central laboratory (Bayer Rapidlab
      860, Tarrytown, NY). Sensor data, after prospective calibration with 6-hourly
      laboratory values using the proprietary Medtronic Minimed Guardian RT algorithm,
      were compared with all laboratory glucose values. Statistical analysis was
      performed to test whether sensor performance was affected by body temperature,
      inotrope dose, or body-wall edema. RESULTS: Twenty patients were enrolled in the
      study for a total of 40 study days and 246 paired sensor and laboratory glucose
      values. Consensus error grid analysis demonstrated that 72.0% of sensor value
      comparisons were within zone A (no effect on clinical action), and 27.6% of
      comparisons were within zone B (altered clinical action of little or no effect on
      outcome), with a mean absolute relative deviation of 17.6% for all comparisons.
      One comparison (0.4%) was in zone C (altered clinical action likely to affect
      outcome). No significant correlations were found between sensor performance and
      body temperature, inotrope dose, or body-wall edema. All patients tolerated the
      sensors well without bleeding or tissue reaction. CONCLUSIONS: Guardian RT real
      time subcutaneous blood glucose measurement is safe and potentially useful for
      continuous glucose monitoring in critically ill children. Subcutaneous sensors
      performed well in the setting of hypothermia, inotrope use, and edema. These
      sensors facilitate identifying and following the effects of interventions to
      control blood glucose.

PMID- 16951014
TI  - Ex uno plures: the concealed complexity of bilirubin species in neonatal blood
      samples.
AB  - Blood from jaundiced neonates often contains several isomers of bilirubin in
      addition to the biosynthetic isomer that causes kernicterus. These isomers are
      generated during phototherapy or during normal exposure of infants to ambient
      light. Their presence is generally overlooked or ignored in clinical measurements
      of circulating bilirubin concentrations and the interpretation of these values.
      Whether this is justified or clinically important is presently uncertain.
      However, the presence of isomers may complicate the accurate measurement of free
      bilirubin concentrations in blood and the use of such values for identifying
      jaundiced infants at most risk of kernicterus.

PMID- 16951015
TI  - Expert committee recommendations for acne management.
AB  - In 2003, an international committee of physicians and researchers in the field of
      acne, working together as the Global Alliance to Improve Outcomes in Acne,
      developed consensus guidelines for the treatment of acne. These guidelines were
      evidence based when possible but also included the extensive clinical experience
      of this group of international dermatologists. As a result of the evaluation of
      available data and the experience, significant changes occurred in the management
      routines for acne. The greatest change arose on the basis of improved
      understanding of acne pathophysiology. The recommendation now is that acne
      treatments should be combined to target as many pathogenic factors as possible. A
      topical retinoid should be the foundation of treatment for most patients with
      acne, because retinoids target the microcomedo, the precursor to all acne
      lesions. Retinoids also are comedolytic and have intrinsic antiinflammatory
      effects, thus targeting 2 pathogenic factors in acne. Combining a topical
      retinoid with an antimicrobial agent targets 3 pathogenic factors, and clinical
      trials have shown that combination therapy results in significantly faster and
      greater clearing as opposed to antimicrobial therapy alone. Oral antibiotics
      should be used only in moderate-to-severe acne, should not be used as
      monotherapy, and should be discontinued as soon as possible (usually within 8-12
      weeks). Because of their effect on the microcomedo, topical retinoids also are
      recommended as an important facet of maintenance therapy.

PMID- 16951016
TI  - Family physicians in the child health care workforce: opportunities for
      collaboration in improving the health of children.
AB  - Pediatric workforce studies suggest that there may be a sufficient number of
      pediatricians for the current and projected US child population. These analyses
      do not fully consider the role of family medicine in the care of children. Family
      physicians provide 16% to 26% of visits for children, providing a medical home
      for one third of the child population, but face shrinking panels of children.
      Family medicine's role in children's health care is more stable in rural
      communities, for adolescents, and for underserved populations. For these
      populations, in particular, family medicine's role remains important. The erosion
      of the proportion of visits to family medicine is likely caused by the rapid rise
      in the number of pediatricians relative to a declining birth rate. Between 1981
      and 2004, the general pediatrician population grew at 7 times the rate of the US
      population, and the family physician workforce grew at nearly 5 times the rate.
      The number of clinicians caring for children meets or exceeds most estimates of
      sufficiency; however, the workforce distribution is skewed, leaving certain
      populations and settings underserved. More than 5 million children and
      adolescents live in counties with no pediatrician. Unmet need, addressing health
      in the context of families and communities, and tackling "millennial morbidities"
      represent common ground for both specialties that could lead to specific,
      collaborative training, research, intervention, and advocacy.

PMID- 16951017
TI  - Optimizing care and outcome for late-preterm (near-term) infants: a summary of
      the workshop sponsored by the National Institute of Child Health and Human
      Development.
AB  - In 2003, 12.3% of births in the United States were preterm (< 37 completed weeks
      of gestation). This represents a 31% increase in the preterm birth rate since
      1981. The largest contribution to this increase was from births between 34 and 36
      completed weeks of gestation (often called the "near term" but referred to as
      "late preterm" in this article). Compared with term infants, late-preterm infants
      have higher frequencies of respiratory distress, temperature instability,
      hypoglycemia, kernicterus, apnea, seizures, and feeding problems, as well as
      higher rates of rehospitalization. However, the magnitude of these morbidities at
      the national level and their public health impact have not been well studied. To
      address these issues, the National Institute of Child Health and Human
      Development of the National Institutes of Health invited a multidisciplinary team
      of experts to a workshop in July 2005 entitled "Optimizing Care and Outcome of
      the Near-Term Pregnancy and the Near-Term Newborn Infant." The participants
      discussed the definition and terminology, epidemiology, etiology, biology of
      maturation, clinical care, surveillance, and public health aspects of late
      preterm infants. Knowledge gaps were identified, and research priorities were
      listed. This article provides a summary of the meeting.

PMID- 16951019
TI  - Should selective serotonin reuptake inhibitors be prescribed for children with
      major depressive and anxiety disorders?

PMID- 16951018
TI  - Stimulants and sudden death: what is a physician to do?
AB  - OBJECTIVE: Recently, a US Food and Drug Administration advisory committee raised
      concerns about cardiovascular risks and sudden death in children and adolescents
      with attention-deficit/hyperactivity disorder who are receiving stimulants.
      METHODS: We comment on the risk of sudden death in children/adolescents taking
      stimulants compared with population rates, biological plausibility, and known
      cardiovascular effects of stimulants to determine specific risk. RESULTS: There
      does not seem to be higher risk of sudden death in stimulant-treated individuals
      compared with the general population. Although there is evidence of biological
      plausibility, the known effects of the stimulants on cardiovascular
      electrophysiology and vital signs seem to be benign. CONCLUSIONS: There does not
      seem to be compelling findings of a medication-specific risk necessitating
      changes in our stimulant treatment of children and adolescents with attention
      deficit/hyperactivity disorder. The use of existing guidelines on the use of
      stimulants (and psychotropic agents) may identify children, adolescents, and
      adults who are vulnerable to sudden death.

PMID- 16951020
TI  - Why don't those ear drops work for my patients?

PMID- 16951021
TI  - A Jacobian future: can everyone have a medical home?

PMID- 16951022
TI  - Sleeping with the enemy: Garfield and the National Heart, Lung, and Blood
      Institute.

PMID- 16951023
TI  - The cartoon character garfield and the "sleep well. Do well. Star sleeper"
      campaign.

PMID- 16951024
TI  - Early pulmonary manifestation of cystic fibrosis in children with the
      DeltaF508/R117H-7T genotype.
AB  - We report 3 cystic fibrosis newborn screen-positive infants with the
      DeltaF508/R117H-7T genotype who had Pseudomonas aeruginosa detected in
      oropharyngeal cultures early in life and a fourth who had pulmonary symptoms and
      Gram-negative growth on multiple oropharyngeal cultures. All 4 patients were
      followed prospectively from the time of genetic diagnosis. As many regions
      implement newborn screening for cystic fibrosis, there is concern regarding which
      mutations should be included in genetic panels used to make the cystic fibrosis
      diagnosis. Some have recommended that mutations not specifically associated with
      classic cystic fibrosis be excluded. Our cases highlight the importance of
      considering keeping so-called mild mutations on cystic fibrosis newborn screening
      panels and the need to follow children with these mutations closely.

PMID- 16951026
TI  - Chemical-biological terrorism and its impact on children.
AB  - Children remain potential victims of chemical or biological terrorism. In recent
      years, children have even been specific targets of terrorist acts. Consequently,
      it is necessary to address the needs that children would face after a terrorist
      incident. A broad range of public health initiatives have occurred since
      September 11, 2001. Although the needs of children have been addressed in many of
      them, in many cases, these initiatives have been inadequate in ensuring the
      protection of children. In addition, public health and health care system
      preparedness for terrorism has been broadened to the so-called all-hazards
      approach, in which response plans for terrorism are blended with plans for a
      public health or health care system response to unintentional disasters (eg,
      natural events such as earthquakes or pandemic flu or manmade catastrophes such
      as a hazardous-materials spill). In response to new principles and programs that
      have appeared over the last 5 years, this policy statement provides an update of
      the 2000 policy statement. The roles of both the pediatrician and public health
      agencies continue to be emphasized; only a coordinated effort by pediatricians
      and public health can ensure that the needs of children, including emergency
      protocols in schools or child care centers, decontamination protocols, and mental
      health interventions, will be successful.

PMID- 16951027
TI  - Lactose intolerance in infants, children, and adolescents.
AB  - The American Academy of Pediatrics Committee on Nutrition presents an updated
      review of lactose intolerance in infants, children, and adolescents. Differences
      between primary, secondary, congenital, and developmental lactase deficiency that
      may result in lactose intolerance are discussed. Children with suspected lactose
      intolerance can be assessed clinically by dietary lactose elimination or by tests
      including noninvasive hydrogen breath testing or invasive intestinal biopsy
      determination of lactase (and other disaccharidase) concentrations. Treatment
      consists of use of lactase-treated dairy products or oral lactase
      supplementation, limitation of lactose-containing foods, or dairy elimination.
      The American Academy of Pediatrics supports use of dairy foods as an important
      source of calcium for bone mineral health and of other nutrients that facilitate
      growth in children and adolescents. If dairy products are eliminated, other
      dietary sources of calcium or calcium supplements need to be provided.

PMID- 16951028
TI  - The use of systemic fluoroquinolones.
AB  - The only indications for which a fluoroquinolone (ie, ciprofloxacin) is licensed
      by the US Food and Drug Administration for use in patients younger than 18 years
      are complicated urinary tract infections, pyelonephritis, and postexposure
      treatment for inhalation anthrax. Nonetheless, approximately 520,000
      prescriptions for fluoroquinolones were written in the United States for patients
      younger than 18 years in 2002; 13,800 were written for infants and children 2 to
      6 years of age, and 2750 were written for infants younger than 2 years. Clinical
      trials of fluoroquinolones in pediatric patients with various diagnoses have been
      published and are reviewed. Fluoroquinolones cause arthrotoxicity in juvenile
      animals and have been associated with reversible musculoskeletal events in both
      children and adults. Other adverse events associated with fluoroquinolones
      include central nervous system disorders, photosensitivity, disorders of glucose
      homeostasis, prolongation of QT interval with rare cases of torsade de pointes
      (often lethal ventricular arrhythmia in patients with long QT syndrome), hepatic
      dysfunction, and rashes. The increased use of fluoroquinolones in adults has
      resulted in increased bacterial resistance to this class of antibacterial agents.
      This report provides specific guidelines for the systemic use of fluoroquinolones
      in children. Fluoroquinolone use should be restricted to situations in which
      there is no safe and effective alternative to treat an infection caused by
      multidrug-resistant bacteria or to provide oral therapy when parenteral therapy
      is not feasible and no other effective oral agent is available.

PMID- 16951029
TI  - Immunization information systems.
AB  - The American Academy of Pediatrics continues to support the development and
      implementation of immunization information systems, previously referred to as
      immunization registries, and other systems for the benefit of children,
      pediatricians, and their communities. Pediatricians and others must be aware of
      the value that immunization information systems have for society, the potential
      fiscal influences on their practice, the costs and benefits, and areas for future
      improvement.

PMID- 16951030
TI  - When is lack of supervision neglect?
AB  - Occasionally, pediatricians become aware of children who are inadequately
      supervised. More frequently, pediatricians treat children for traumatic injuries
      or ingestions that they suspect could have been prevented with better
      supervision. This clinical report contains guidance for pediatricians considering
      a referral to a child protective services agency on the basis of suspicion of
      supervisory neglect.

PMID- 16951031
TI  - Evaluating infants and young children with multiple fractures.
AB  - Infants and toddlers with multiple unexplained fractures are often victims of
      inflicted injury. However, several medical conditions can also cause multiple
      fractures in children in this age group. In this report, the differential
      diagnosis of multiple fractures is presented, and diagnostic testing available to
      the clinician is discussed. The hypothetical entity "temporary brittle-bone
      disease" is examined also. Although frequently offered in court cases as a cause
      of multiple infant fractures, there is no evidence that this condition actually
      exists.

PMID- 16951032
TI  - The Apgar score.

PMID- 16951033
TI  - The Apgar score.

PMID- 16951034
TI  - The Apgar score.

PMID- 16951035
TI  - Physiological doses of corticosteroids for premature infants.

PMID- 16951036
TI  - Effect of timing of cord clamping on neonatal venous hematocrit values and
      clinical outcome at term: a randomized, controlled trial.

PMID- 16951037
TI  - A randomized trial of home oxygen therapy from the emergency department for acute
      bronchiolitis.

PMID- 16951038
TI  - Evaluation of nonpharmacologic methods of pain and anxiety management for
      laceration repair in the pediatric emergency department.

PMID- 16951039
TI  - Methamphetamine-induced sensitization differentially alters pCREB and DeltaFosB
      throughout the limbic circuit of the mammalian brain.
AB  - Enhancements in behavior that accompany repeated, intermittent administration of
      abused drugs (sensitization) endure long after drug administration has ceased.
      Such persistence reflects changes in intracellular signaling cascades and
      associated gene transcription factors in brain regions that are engaged by abused
      drugs. This process is not characterized for the most potent psychomotor
      stimulant, methamphetamine. Using motor behavior as an index of brain state in
      rats, we verified that five once-daily injections of 2.5 mg/kg methamphetamine
      induced behavioral sensitization that was demonstrated (expressed) 3 and 14 days
      later. Using immunoblot procedures, limbic brain regions implicated in behavioral
      sensitization were assayed for extracellular signal-regulated kinase and its
      phosphorylated form (pERK/ERK, a signal transduction kinase), cAMP response
      element binding protein and its phosphorylated form (pCREB/CREB, a constitutively
      expressed transcriptional regulator), and DeltaFosB (a long-lasting transcription
      factor). pERK, ERK, and CREB levels were not changed for any region assayed. In
      the ventral tegmental area, pCREB and DeltaFosB also were not changed. pCREB
      (activated CREB) was elevated in the frontal cortex at 3 days withdrawal, but not
      at 14 days. pCREB levels were decreased at 14 days withdrawal in the nucleus
      accumbens and ventral pallidum. Accumbal and pallidal levels of DeltaFosB were
      increased at 3 days withdrawal, and this increase persisted to 14 days in the
      pallidum. Thus, only the ventral pallidum showed changes in molecular processes
      that consistently correlated with motor sensitization, revealing that this region
      may be associated with this enduring behavioral phenotype initiated by
      methamphetamine. The present findings expand our understanding of the
      neuroanatomical and molecular substrates that may play a role in the persistence
      of druginduced sensitization.

PMID- 16951040
TI  - Does coronary vasodilation after adenosine override endothelin-1-induced coronary
      vasoconstriction?
AB  - Endothelin-1 is a powerful coronary vasoconstrictor that is overexpressed in
      coronary artery disease. Adenosine is a powerful coronary vasodilator used for
      myocardial perfusion imaging to identify flow-limiting coronary artery stenosis.
      Therefore, in an animal model we tested the hypothesis that intracoronary
      endothelin-1 may cause myocardial perfusion abnormalities by positron emission
      tomography (PET) at resting conditions that may persist or only partially improve
      after intravenous adenosine stress in the absence of myocardial scar and flow
      limiting stenosis. Fourteen dogs underwent serial PET perfusion imaging with
      rubidium-82 before and after subselective intracoronary infusion of endothelin-1,
      followed by intravenous and then intracoronary adenosine. Small physiological
      doses of endothelin-1 infused into the mid-left circumflex coronary artery caused
      quantitatively significant resting perfusion abnormalities that normalized after
      intracoronary adenosine but not consistently after intravenous adenosine used for
      diagnostic imaging. After effects of adenosine abated, resting perfusion defects
      returned, lasting up to 5 h in some animals. Cumulative doses of endothelin-1
      caused perfusion defects that did not normalize after intravenous adenosine. In
      an animal model without myocardial scar or flow-limiting stenosis, intracoronary
      endothelin-1 causes visually apparent, quantitatively significant, long-lasting
      myocardial perfusion defects at resting conditions that may persist or only
      partially improve after intravenous adenosine used for diagnostic imaging. These
      results may potentially explain resting perfusion abnormalities or heterogeneity
      by clinical PET that may persist or only partially improve after adenosine stress
      perfusion imaging in the absence of myocardial scar and flow-limiting stenosis.

PMID- 16951041
TI  - Editorial commentary on pulsatile blood flow in the entire coronary arterial
      tree: theory and experiment.

PMID- 16951042
TI  - Alpha-Adrenergic receptor responsiveness is preserved during prolonged exercise.
AB  - Our laboratory has previously reported a decline in sympathetic nervous system
      restraint of skeletal muscle blood flow during prolonged mild-intensity exercise.
      This decline may be explained by a decrease in alpha(1)- and alpha(2)-adrenergic
      receptor responsiveness over time. Thus the purpose of the present study was to
      investigate the effect of exercise duration on alpha(1)- and alpha(2)-adrenergic
      receptor responsiveness during prolonged constant-load exercise. Mongrel dogs (n
      = 6) were instrumented chronically with transit-time flow probes on the external
      iliac arteries and an indwelling catheter in a branch of the femoral artery. On
      separate days, flow-adjusted doses of selective alpha(1)- (phenylephrine)
      alpha(2)-adrenergic-receptor (clonidine) agonists, and tyramine (to evoke
      endogenous norepinephrine release) were infused following 5, 30 and 50 min of
      mild-intensity treadmill exercise (3 miles/h), with hindlimb blood flow (HBF) and
      mean arterial pressure (MAP) monitored continuously. Vascular conductance (VC)
      was calculated as HBF/MAP. While the dogs ran on the treadmill at 3 miles/h,
      infusion of phenylephrine resulted in similar decreases in VC after 5 [73% (SD
      10)], 30 [76% (SD 9)], and 50 [73% (SD 10)] min of exercise. Infusion of the
      alpha(2)-agonist clonidine also produced similar decreases in VC after 5 [58% (SD
      10)], 30 [58% (SD 11)], and 50 [53% (SD 12)] min of exercise. Infusion of
      tyramine resulted in similar decreases in VC after 5 [55% (SD 15)], 30 [51% (SD
      10)], and 50 [50% (SD 7)] min of exercise. These results demonstrate that
      alpha(1)- and alpha(2)-adrenergic receptor responsiveness to infusion of
      selective alpha(1)- and alpha(2)-adrenergic-receptor agonists and endogenous
      norepinephrine release (tyramine) does not decline during prolonged mild
      intensity exercise. Thus a decrease in alpha-adrenergic receptor responsiveness
      over time does not appear to be responsible for the decrease in sympathetic
      restraint of muscle blood flow during prolonged exercise.

PMID- 16951043
TI  - Superoxide mediates acute renal vasoconstriction produced by angiotensin II and
      catecholamines by a mechanism independent of nitric oxide.
AB  - NAD(P)H oxidases (NOX) and reactive oxygen species (ROS) are involved in
      vasoconstriction and vascular remodeling during hypertension produced by chronic
      angiotensin II (ANG II) infusion. These effects are thought to be mediated
      largely through superoxide anion (O(2)(-)) scavenging of nitric oxide (NO).
      Little is known about the role of ROS in acute vasoconstrictor responses to
      agonists. We investigated renal blood flow (RBF) reactivity to ANG II (4 ng),
      norepinephrine (NE, 20 ng), and alpha(1)-adrenergic agonist phenylephrine (PE,
      200 ng) injected into the renal artery (ira) of anesthetized Sprague-Dawley rats.
      The NOX inhibitor apocynin (1-4 mg.kg(-1).min(-1) ira, 2 min) or the superoxide
      dismutase mimetic Tempol (1.5-5 mg.kg(-1).min(-1) ira, 2 min) rapidly increased
      resting RBF by 8 +/- 1% (P < 0.001) or 3 +/- 1% (P < 0.05), respectively. During
      NO synthase (NOS) inhibition (N(omega)-nitro-l-arginine methyl ester, 25 mg/kg
      iv), the vasodilation tended to increase (apocynin 13 +/- 4%, Tempol 10 +/- 1%).
      During control conditions, both ANG II and NE reduced RBF by 24 +/- 4%. Apocynin
      dose dependently reduced the constriction by up to 44% (P < 0.05). Similarly,
      Tempol blocked the acute actions of ANG II and NE by up to 48-49% (P < 0.05). In
      other animals, apocynin (4 mg.kg(-1).min(-1) ira) attenuated vasoconstriction to
      ANG II, NE, and PE by 46-62% (P < 0.01). During NOS inhibition, apocynin reduced
      the reactivity to ANG II and NE by 60-72% (P < 0.01), and Tempol reduced it by 58
      66% (P < 0.001). We conclude that NOX-derived ROS substantially contribute to
      basal RBF as well as to signaling of acute renal vasoconstrictor responses to ANG
      II, NE, and PE in normal rats. These effects are due to O(2)(-) rather than
      H(2)O(2), occur rapidly, and are independent of scavenging of NO.

PMID- 16951044
TI  - A reevaluation of the roles of hexokinase I and II in the heart.
AB  - Hexokinase is responsible for glucose phosphorylation, a process fundamental to
      regulating glucose uptake. In some tissues, hexokinase translocates to the
      mitochondria, thereby increasing its efficiency and decreasing its susceptibility
      to product inhibition. It may also decrease free radical formation in the
      mitochondria and prevent apoptosis. Whether hexokinase translocation occurs in
      the heart is controversial; here, using immunogold labeling for the first time,
      we provide evidence for this process. Rat hearts (6 groups, n = 6/group),
      perfused with either glucose- or glucose + oleate (0.4 mmol/l)-containing buffer,
      were exposed to 30-min insulin stimulation, ischemia, or control perfusion.
      Hexokinase I (HK I) and hexokinase II (HK II) distributions were then determined.
      In glucose-perfused hearts, HK I-mitochondrial binding increased from 0.41 +/-
      0.04 golds/mm in control hearts to 0.71 +/- 0.10 golds/mm after insulin and to
      1.54 +/- 0.38 golds/mm after ischemia (P < 0.05). Similarly, HK II-mitochondrial
      binding increased from 0.16 +/- 0.02 to 0.53 +/- 0.08 golds/mm with insulin and
      0.44 +/- 0.07 golds/mm after ischemia (P < 0.05). Under basal conditions, the
      fraction of HK I that was mitochondrial bound was five times greater than for HK
      II; insulin and ischemia caused a fourfold increase in HK II binding but only a
      doubling in HK I binding. Oleate decreased hexokinase-mitochondrial binding and
      abolished insulin-mediated translocation of HK I. Our data show that
      mitochondrial-hexokinase binding increases under insulin or ischemic stimulation
      and that this translocation is modified by oleate. These events are isoform
      specific, suggesting that HK I and HK II are independently regulated and implying
      that they perform different roles in cardiac glucose regulation.

PMID- 16951045
TI  - Role of PKC in the novel synergistic action of urotensin II and angiotensin II
      and in urotensin II-induced vasoconstriction.
AB  - The intracellular signaling of human urotensin II (hU-II) and its interaction
      with other vasoconstrictors such as ANG II are poorly understood. In endothelium
      denuded rat aorta, coadministration of hU-II (1 nM) and ANG II (2 nM) exerted a
      significant contractile effect that was associated with increased protein kinase
      C (PKC) activity and phosphorylation of PKC-alpha/betaII and myosin light chain,
      whereas either hU-II or ANG II administered alone at these concentrations had no
      statistically significant effect. This synergistic effect was abrogated by the
      PKC inhibitor chelerythrine (10 and 30 microM), the selective PKC-alpha/betaII
      inhibitor Go-6976 (0.1 and 1 microM), the hU-II receptor ligand urantide (30 nM
      and 1 microM), or the ANG II antagonist losartan (1 microM). Moreover, in
      endothelium-intact rat aorta, the synergistic effect of hU-II and ANG II was not
      exerted any longer, and this synergistic effect was unmasked by pretreatment of
      the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester. hU-II (10
      nM) alone caused a long-lasting increase in phospho-PKC-theta, phospho-myosin
      light chain, and PKC activity, which was associated with long-lasting
      vasoconstriction. These changes were prevented by chelerythrine. Methoxyverapamil
      thapsigargin treatment reduced the hU-II-induced vasoconstriction by
      approximately 50%. The methoxyverapamil-thapsigargin-resistant component of hU-II
      induced vasoconstriction was dose-dependently inhibited by chelerythrine. In
      conclusion, hU-II induces a novel PKC-dependent synergistic action with ANG II in
      inducing vasoconstriction. PKC-alpha/betaII is probably the PKC isoform involved
      in this synergistic action. Nitric oxide produced in the endothelium probably
      masks this synergistic action. The long-lasting vasoconstriction induced by hU-II
      alone is PKC dependent and associated with PKC-theta phosphorylation.

PMID- 16951046
TI  - Streptozotocin-induced diabetes progressively increases blood-brain barrier
      permeability in specific brain regions in rats.
AB  - This study investigated the effects of streptozotocin-induced diabetes on the
      functional integrity of the blood-brain barrier in the rat at 7, 28, 56, and 90
      days, using vascular space markers ranging in size from 342 to 65,000 Da. We also
      examined the effect of insulin treatment of diabetes on the formation and
      progression of cerebral microvascular damage and determined whether observed
      functional changes occurred globally throughout the brain or within specific
      brain regions. Results demonstrate that streptozotocin-induced diabetes produced
      a progressive increase in blood-brain barrier permeability to small molecules
      from 28 to 90 days and these changes in blood-brain barrier permeability were
      region specific, with the midbrain most susceptible to diabetes-induced
      microvascular damage. In addition, results showed that insulin treatment of
      diabetes attenuated blood-brain barrier disruption, especially during the first
      few weeks; however, as diabetes progressed, it was evident that microvascular
      damage occurred even when hyperglycemia was controlled. Overall, results of this
      study suggest that diabetes-induced perturbations to cerebral microvessels may
      disrupt homeostasis and contribute to long-term cognitive and functional deficits
      of the central nervous system.

PMID- 16951047
TI  - Exogenous IL-10 overexpression reduces perforin production by activated allogenic
      CD8+ cells and prolongs cardiac allograft survival.
AB  - Perforin is a cytolytic mediator produced by cytotoxic T cells (CD8(+) cells) and
      natural killer cells. We previously reported that ex vivo IL-10 gene therapy
      induced apoptosis of allogenic infiltrative CD8(+) cells and significantly
      prolonged cardiac allograft survival. To further test the hypothesis that
      localized IL-10 overexpression in cardiac allografts may also effect the
      alloreactive CD8(+) T cell function by downregulating its perforin production, we
      used a rabbit functional heterotopic allograft heart transplant model. Human
      recombinant IL-10 gene complexed with liposome was intracoronary delivered into
      the cardiac allografts ex vivo. The percentage of apoptotic infiltrative CD8(+)
      cells in cardiac allografts was increased 6-fold in the gene therapy group vs.
      the control group, whereas the percentage of perforin-positive CD8(+) cells was
      decreased 2.9-fold (P < 0.01). Perforin expression level in the allograft
      myocardium of the gene therapy group was deceased 3.2-fold (P < 0.01). The amount
      of infiltrative perforin-positive CD8(+) cells and perforin expression level were
      inversely correlated with IL-10 transgene and protein expression level in the
      myocardium of cardiac allografts (P < 0.01), the percentage of apoptotic cardiac
      myocytes (P < 0.01), and the peak left ventricular systolic pressure of cardiac
      allografts (P < 0.01) but significantly correlated with the infiltrative T cell
      cytotoxicity (P < 0.01) and allograft rejection score (P < 0.01). These results
      suggest that localized IL-10 gene therapy prolongs cardiac allograft survival, at
      least in part, through downregulation of perforin production by activated
      allogenic CD8(+) T cells. Reduction of cytolytic function of cytotoxic effector
      cells prevents the apoptosis of cardiac myocytes.

PMID- 16951048
TI  - Sildenafil-mediated acute cardioprotection is independent of the NO/cGMP pathway.
AB  - Sildenafil, a potent inhibitor of phosphodiesterase type 5, has recently been
      investigated in animal models of myocardial ischemia-reperfusion (MI/R) injury.
      Previous studies have suggested that the protective effects of sildenafil are
      mediated via activation of endothelial nitric oxide (NO) synthesis (eNOS) and
      inducible NOS (iNOS). To further investigate the protective mechanism of
      sildenafil, we subjected wild-type, eNOS, and iNOS null animals to 30 min of
      myocardial ischemia and 24 h of reperfusion. Treatment with 0.06 mg/kg sildenafil
      5 min before reperfusion significantly reduced myocardial infarct size in wild
      type, eNOS null mice (eNOS(-/-)), and iNOS(-/-) animals. Additionally, the low
      dose utilized in this study did not alter myocardial cGMP. These results suggest
      that acute low-dose sildenafil-mediated cardioprotection is independent of eNOS,
      iNOS, and cGMP. In a second series of experiments, we investigated sildenafil in
      db/db diabetic mice subjected to MI/R. We found that sildenafil failed to protect
      diabetic mice against MI/R. However, NO(.) donor therapy was found to
      significantly protect against MI/R injury in both nondiabetic and diabetic mice,
      suggesting that protection could be conferred in diabetic mice and that the
      upstream modulator of soluble guanylyl cyclase, NO(.), may mediate protection
      independent of cGMP signaling. The present study suggests that further research
      is needed to delineate the precise mechanisms by which sildenafil exerts
      cardioprotection.

PMID- 16951049
TI  - Cyclic strain-mediated matrix metalloproteinase regulation within the vascular
      endothelium: a force to be reckoned with.
AB  - The vascular endothelium is a dynamic cellular interface between the vessel wall
      and the bloodstream, where it regulates the physiological effects of humoral and
      biomechanical stimuli on vessel tone and remodeling. With respect to the latter
      hemodynamic stimulus, the endothelium is chronically exposed to mechanical forces
      in the form of cyclic circumferential strain, resulting from the pulsatile nature
      of blood flow, and shear stress. Both forces can profoundly modulate endothelial
      cell (EC) metabolism and function and, under normal physiological conditions,
      impart an atheroprotective effect that disfavors pathological remodeling of the
      vessel wall. Moreover, disruption of normal hemodynamic loading can be either
      causative of or contributory to vascular diseases such as atherosclerosis. EC
      matrix interactions are a critical determinant of how the vascular endothelium
      responds to these forces and unquestionably utilizes matrix metalloproteinases
      (MMPs), enzymes capable of degrading basement membrane and interstitial matrix
      molecules, to facilitate force-mediated changes in vascular cell fate. In view of
      the growing importance of blood flow patterns and mechanotransduction to vascular
      health and pathophysiology, and considering the potential value of MMPs as
      therapeutic targets, a timely review of our collective understanding of MMP
      mechanoregulation and its impact on the vascular endothelium is warranted. More
      specifically, this review primarily summarizes our current knowledge of how
      cyclic strain regulates MMP expression and activation within the vascular
      endothelium and subsequently endeavors to address the direct and indirect
      consequences of this on vascular EC fate. Possible relevance of these phenomena
      to vascular endothelial dysfunction and pathological remodeling are also
      addressed.

PMID- 16951050
TI  - Baroreflex responses to electrical stimulation of aortic depressor nerve in
      conscious SHR.
AB  - Baroreflex responses to changes in arterial pressure are impaired in
      spontaneously hypertensive rats (SHR). Mean arterial pressure (MAP), heart rate
      (HR), and regional vascular resistances were measured before and during
      electrical stimulation (5-90 Hz) of the left aortic depressor nerve (ADN) in
      conscious SHR and normotensive control rats (NCR). The protocol was repeated
      after beta-adrenergic-receptor blockade with atenolol. SHR exhibited higher basal
      MAP (150 +/- 5 vs. 103 +/- 2 mmHg) and HR (393 +/- 9 vs. 360 +/- 5 beats/min).
      The frequency-dependent hypotensive response to ADN stimulation was preserved or
      enhanced in SHR. The greater absolute fall in MAP at higher frequencies (-68 +/-
      5 vs. -38 +/- 3 mmHg at 90-Hz stimulation) in SHR was associated with a
      preferential decrease in hindquarter (-43 +/- 5%) vs. mesenteric (-27 +/- 3%)
      resistance. In contrast, ADN stimulation decreased hindquarter and mesenteric
      resistances equivalently in NCR (-33 +/- 7% and -30 +/- 7%). Reflex bradycardia
      was also preserved in SHR, although its mechanism differed. Atenolol attenuated
      the bradycardia in SHR (-88 +/- 14 vs. -129 +/- 18 beats/min at 90-Hz
      stimulation) but did not alter the bradycardia in NCR (-116 +/- 16 vs. -133 +/-
      13 beats/min). The residual bradycardia under atenolol (parasympathetic
      component) was reduced in SHR. MAP and HR responses to ADN stimulation were also
      preserved or enhanced in SHR vs. NCR after deafferentation of carotid sinuses and
      contralateral right ADN. The results demonstrate distinct differences in central
      baroreflex control in conscious SHR vs. NCR. Inhibition of cardiac sympathetic
      tone maintains reflex bradycardia during ADN stimulation in SHR despite impaired
      parasympathetic activation, and depressor responses to ADN stimulation are
      equivalent or even greater in SHR due to augmented hindquarter vasodilation.

PMID- 16951051
TI  - Improved postischemic function following acute exercise is not mediated by nitric
      oxide synthase in the rat heart.
AB  - The mediators of acute exercise-induced preconditioning against ischemia
      reperfusion injury are not understood. This study assesses the role of nitric
      oxide synthase (NOS), a reported mediator of other forms of preconditioning. Male
      Fischer 344 rats were divided into five groups (n = 6-7): sedentary (Sed);
      exercised 2 days on a treadmill at 20 m/min, 6 degrees grade, for 60 min (Run);
      sedentary, perfused with 100 microM N(omega)-nitro-l-arginine methyl ester
      hydrochloride (l-NAME) to inhibit NOS (Sed/L-N); exercised, perfused with l-NAME
      (Run/L-N); and exercised in a 4 degrees C environment, perfused with l-NAME
      (CRun/L-N). Twenty-four hours following exercise, isolated, perfused working
      hearts were subjected to 22.5 min of global ischemia plus 30 min of normoxic
      reperfusion. Left ventricle contents of several putative preconditioning
      mediators were determined. Postischemic recovery of cardiac output times systolic
      pressure was better in Run than Sed (78.4 vs. 50.2% of preischemia, P < 0.05).
      Inhibition of NOS did not abrogate the improved recovery in the exercise groups
      or alter recovery in Sed. All exercise groups also displayed improved myocardial
      efficiency (cardiac output times systolic pressure/oxygen consumption)
      postischemia and less lactate dehydrogenase release (P < 0.05). l-NAME appeared
      to lower lactate dehydrogenase release independent of exercise. The only change
      in antioxidant enzyme activity was a decrease in manganese superoxide dismutase
      in CRun/L-N (P < 0.05). Heat shock protein 72 expression increased only in Run
      and Run/L-N and endothelial NOS only in CRun/L-N (P < 0.05). Acute exercise
      induced preconditioning of the Fischer 344 rat heart is not mediated by NOS and
      does not require increases in heat shock protein 72 or antioxidant enzymes.

PMID- 16951052
TI  - Short-cycle hypoxia in the intact heart: hypoxia-inducible factor 1alpha
      signaling and the relationship to injury threshold.
AB  - Hypoxia-inducible factor 1alpha (HIF-1alpha) transcriptionally activates multiple
      genes, which regulate metabolic cardioprotective and cross-adaptive mechanisms.
      Hypoxia and several other stimuli induce the HIF-1alpha signaling cascade,
      although little data exist regarding the stress threshold for activation in
      heart. We tested the hypothesis that relatively mild short-cycle hypoxia, which
      produces minimal cardiac dysfunction and no sustained or major disruption in
      energy state, can induce HIF-1alpha activation. We developed a short-cycle
      hypoxia protocol in isolated perfused rabbit heart to test this hypothesis. By
      altering cycling conditions, we identified a specific cycle with O(2) content and
      duration that operated near a threshold for causing functional injury in these
      rabbit hearts. Mild short-cycle hypoxia for 46 min elevated HIF-1alpha mRNA and
      protein within 45 min after reoxygenation. Expression also increased for multiple
      HIF-1alpha target genes, such as VEGF and heme oxygenase 1. After mild hypoxia,
      VEGF protein accumulation occurred, although HIF-1alpha and VEGF protein
      accumulation were suppressed after more severe hypoxia, which also caused
      depletion of ATP and nondiffusible nucleotides. In summary, these results
      indicate that mild near-threshold hypoxia induces HIF-1alpha cascade, but more
      severe hypoxia suppresses protein accumulation for this transcription factor and
      the target genes. Posttranscriptional suppression of these proteins occurs under
      conditions of altered energy state, exemplified by ATP depletion.

PMID- 16951054
TI  - Mapping PrBn and other quantitative trait loci responsible for the control of
      homeologous chromosome pairing in oilseed rape (Brassica napus L.) haploids.
AB  - In allopolyploid species, fair meiosis could be challenged by homeologous
      chromosome pairing and is usually achieved by the action of homeologous pairing
      suppressor genes. Oilseed rape (Brassica napus) haploids (AC, n=19) represent an
      attractive model for studying the mechanisms used by allopolyploids to ensure the
      diploid-like meiotic pairing pattern. In oilseed rape haploids, homeologous
      chromosome pairing at metaphase I was found to be genetically based and
      controlled by a major gene, PrBn, segregating in a background of polygenic
      variation. In this study, we have mapped PrBn within a 10-cM interval on the C
      genome linkage group DY15 and shown that PrBn displays incomplete penetrance or
      variable expressivity. We have identified three to six minor QTL/BTL that have
      slight additive effects on the amount of pairing at metaphase I but do not
      interact with PrBn. We have also detected a number of other loci that interact
      epistatically, notably with PrBn. Our results support the idea that, as in other
      polyploid species, metaphase I homeologous pairing in oilseed rape haploids is
      controlled by an integrated system of several genes, which function in a complex
      manner.

PMID- 16951053
TI  - dSno facilitates baboon signaling in the Drosophila brain by switching the
      affinity of Medea away from Mad and toward dSmad2.
AB  - A screen for modifiers of Dpp adult phenotypes led to the identification of the
      Drosophila homolog of the Sno oncogene (dSno). The dSno locus is large,
      transcriptionally complex and contains a recent retrotransposon insertion that
      may be essential for dSno function, an intriguing possibility from the
      perspective of developmental evolution. dSno is highly transcribed in the
      embryonic central nervous system and transcripts are most abundant in third
      instar larvae. dSno mutant larvae have proliferation defects in the optic lobe of
      the brain very similar to those seen in baboon (Activin type I receptor) and
      dSmad2 mutants. This suggests that dSno is a mediator of Baboon signaling. dSno
      binds to Medea and Medea/dSno complexes have enhanced affinity for dSmad2.
      Alternatively, Medea/dSno complexes have reduced affinity for Mad such that, in
      the presence of dSno, Dpp signaling is antagonized. We propose that dSno
      functions as a switch in optic lobe development, shunting Medea from the Dpp
      pathway to the Activin pathway to ensure proper proliferation. Pathway switching
      in target cells is a previously unreported mechanism for regulating TGFbeta
      signaling and a novel function for Sno/Ski family proteins.

PMID- 16951055
TI  - A histone methylation-dependent DNA methylation pathway is uniquely impaired by
      deficiency in Arabidopsis S-adenosylhomocysteine hydrolase.
AB  - S-adenosylhomocysteine hydrolase (SAH) is a key enzyme in the maintenance of
      methylation homeostasis in eukaryotes because it is needed to metabolize the by
      product of transmethylation reactions, S-adenosylhomocysteine (AdoHcy), which
      causes by-product inhibition of methyltransferases (MTase's). Complete loss of
      SAH function is lethal. Partial loss of SAH function causes pleiotropic effects
      including developmental abnormalities and reduced cytosine methylation. Here we
      describe a novel partial-function missense allele of the Arabidopsis SAH1 gene
      that causes loss of cytosine methylation specifically in non-CG contexts
      controlled by the CMT3 DNA MTase and transcriptional reactivation of a silenced
      reporter gene, without conferring developmental abnormalities. The CMT3 pathway
      depends on histone H3 lysine 9 methylation (H3 mK9) to guide DNA methylation. Our
      results suggest that this pathway is uniquely sensitive to SAH impairment because
      of its requirement for two transmethylation reactions that can both be inhibited
      by AdoHcy. Our results further suggest that gene silencing pathways involving an
      interplay between histone and DNA methylation in other eukaryotes can be
      selectively impaired by controlled SAH downregulation.

PMID- 16951056
TI  - Doubly uniparental inheritance is associated with high polymorphism for
      rearranged and recombinant control region haplotypes in Baltic Mytilus trossulus.
AB  - Many bivalve species, including mussels of the genus Mytilus, are unusual in
      having two mtDNA genomes, one inherited maternally (the F genome) and the other
      inherited paternally (the M genome). The sequence differences between the genomes
      are usually great, indicating ancient divergence predating speciation events.
      However, in Mytilus trossulus from the Baltic, both genomes are similar to the F
      genome from the closely related M. edulis. This study analyzed the mtDNA control
      region structure in male and female Baltic M. trossulus mussels. We show that a
      great diversity of structural rearrangements is present in both sexes. Sperm
      samples are dominated by recombinant haplotypes with M. edulis M-like control
      region segments, some having large duplications. By contrast, the rearranged
      haplotypes that dominate in eggs lack segments from this M genome. The
      rearrangements can be explained by a combination of tandem duplication, deletion,
      and intermolecular recombination. An evolutionary pathway leading to the
      recombinant haplotypes is suggested. The data are also considered in relation to
      the hypothesis that the M. edulis M-like control region sequence is necessary to
      confer the paternal role on genomes that are otherwise F-like.

PMID- 16951057
TI  - Testing for effects of recombination rate on nucleotide diversity in natural
      populations of Arabidopsis lyrata.
AB  - We investigated DNA sequence diversity for loci on chromosomes 1 and 2 in six
      natural populations of Arabidopsis lyrata and tested for the role of natural
      selection in structuring genomewide patterns of variability, specifically
      examining the effects of recombination rate on levels of silent polymorphism. In
      contrast with theoretical predictions from models of genetic hitchhiking, maximum
      likelihood-based analyses of diversity and divergence do not suggest reduction of
      diversity in the region of suppressed recombination near the centromere of
      chromosome 1, except in a single population from Russia, in which the
      pericentromeric region may have undergone a local selective sweep or demographic
      process that reduced variability. We discuss various possibilities that might
      explain why nucleotide diversity in most A. lyrata populations is not related to
      recombination rate, including genic recombination hotspots, and low gene density
      in the low recombination rate region.

PMID- 16951058
TI  - Combining bioinformatics and phylogenetics to identify large sets of single-copy
      orthologous genes (COSII) for comparative, evolutionary and systematic studies: a
      test case in the euasterid plant clade.
AB  - We report herein the application of a set of algorithms to identify a large
      number (2869) of single-copy orthologs (COSII), which are shared by most, if not
      all, euasterid plant species as well as the model species Arabidopsis. Alignments
      of the orthologous sequences across multiple species enabled the design of
      "universal PCR primers," which can be used to amplify the corresponding orthologs
      from a broad range of taxa, including those lacking any sequence databases.
      Functional annotation revealed that these conserved, single-copy orthologs encode
      a higher-than-expected frequency of proteins transported and utilized in
      organelles and a paucity of proteins associated with cell walls, protein kinases,
      transcription factors, and signal transduction. The enabling power of this new
      ortholog resource was demonstrated in phylogenetic studies, as well as in
      comparative mapping across the plant families tomato (family Solanaceae) and
      coffee (family Rubiaceae). The combined results of these studies provide
      compelling evidence that (1) the ancestral species that gave rise to the core
      euasterid families Solanaceae and Rubiaceae had a basic chromosome number of x=11
      or 12.2) No whole-genome duplication event (i.e., polyploidization) occurred
      immediately prior to or after the radiation of either Solanaceae or Rubiaceae as
      has been recently suggested.

PMID- 16951059
TI  - High-resolution quantitative trait locus analysis reveals multiple diabetes
      susceptibility loci mapped to intervals<800 kb in the species-conserved Niddm1i
      of the GK rat.
AB  - Niddm1i, a 16-Mb locus within the major diabetes QTL in the diabetic GK rat,
      causes impaired glucose tolerance in the congenic NIDDM1I strain. Niddm1i is
      homologous to both human and mouse regions linked with type 2 diabetes
      susceptibility. We employed multiple QTL analyses of congenic F2 progeny selected
      for one recombination event within Niddm1i combined with characterization of
      subcongenic strains. Fine mapping located one hyperglycemia locus within 700 kb
      (Niddm1i4, P=5x10(-6)). Two adjacent loci were also detected, and the GK allele
      at Niddm1i2 (500 kb) showed a glucose-raising effect, whereas it had a glucose
      lowering effect at Niddm1i3 (400 kb). Most proximally, Niddm1i1 (800 kb)
      affecting body weight was identified. Experimental data from subcongenics
      supported the four loci. Sorcs1, one of the two known diabetes susceptibility
      genes in the region, resides within Niddm1i3, while Tcf7l2 maps outside all four
      loci. Multiple-marker QTL analysis incorporating the effect of cosegregating QTL
      as cofactors together with genetically selected progeny can remarkably enhance
      resolution of QTL. The data demonstrate that the species-conserved Niddm1i is a
      composite of at least four QTL affecting type 2 diabetes susceptibility and that
      two adjacent QTL (Niddm1i2GK and Niddm1i3GK) act in opposite directions.

PMID- 16951060
TI  - Sequence diversity, reproductive isolation and species concepts in Saccharomyces.
AB  - Using the biological species definition, yeasts of the genus Saccharomyces sensu
      stricto comprise six species and one natural hybrid. Previous work has shown that
      reproductive isolation between the species is due primarily to sequence
      divergence acted upon by the mismatch repair system and not due to major gene
      differences or chromosomal rearrangements. Sequence divergence through mismatch
      repair has also been shown to cause partial reproductive isolation among
      populations within a species. We have surveyed sequence variation in populations
      of Saccharomyces sensu stricto yeasts and measured meiotic sterility in hybrids.
      This allows us to determine the divergence necessary to produce the reproductive
      isolation seen among species. Rather than a sharp transition from fertility to
      sterility, which may have been expected, we find a smooth monotonic relationship
      between diversity and reproductive isolation, even as far as the well-accepted
      designations of S. paradoxus and S. cerevisiae as distinct species. Furthermore,
      we show that one species of Saccharomyces--S. cariocanus--differs from a
      population of S. paradoxus by four translocations, but not by sequence. There is
      molecular evidence of recent introgression from S. cerevisiae into the European
      population of S. paradoxus, supporting the idea that in nature the boundary
      between these species is fuzzy.

PMID- 16951061
TI  - Pronounced differences of recombination activity at the sex determination locus
      of the honeybee, a locus under strong balancing selection.
AB  - Recombination decreases the association of linked nucleotide sites and can
      influence levels of polymorphism in natural populations. When coupled with
      selection, recombination may relax potential conflict among linked genes, a
      concept that has played a central role in research on the evolution of
      recombination. The sex determination locus (SDL) of the honeybee is an
      informative example for exploring the combined forces of recombination,
      selection, and linkage on sequence evolution. Balancing selection at SDL is very
      strong and homozygous individuals at SDL are eliminated by worker bees. The
      recombination rate is increased up to four times that of the genomewide average
      in the region surrounding SDL. Analysis of nucleotide diversity (pi) reveals a
      sevenfold increase of polymorphism within the sex determination gene
      complementary sex determiner (csd) that rapidly declines within 45 kb to levels
      of genomewide estimates. Although no recombination was observed within SDL, which
      contains csd, analyses of heterogeneity, shared polymorphic sites, and linkage
      disequilibrium (LD) show that recombination has contributed to the evolution of
      the 5' part of some csd sequences. Gene conversion, however, has not obviously
      contributed to the evolution of csd sequences. The local control of recombination
      appears to be related to SDL function and mode of selection. The homogenizing
      force of recombination is reduced within SDL, which preserves allelic differences
      and specificity, while the increase of recombination activity around SDL relaxes
      conflict between SDL and linked genes.

PMID- 16951063
TI  - Statistical tests for detecting positive selection by utilizing high-frequency
      variants.
AB  - By comparing the low-, intermediate-, and high-frequency parts of the frequency
      spectrum, we gain information on the evolutionary forces that influence the
      pattern of polymorphism in population samples. We emphasize the high-frequency
      variants on which positive selection and negative (background) selection exhibit
      different effects. We propose a new estimator of theta (the product of effective
      population size and neutral mutation rate), thetaL, which is sensitive to the
      changes in high-frequency variants. The new thetaL allows us to revise Fay and
      Wu's H-test by normalization. To complement the existing statistics (the H-test
      and Tajima's D-test), we propose a new test, E, which relies on the difference
      between thetaL and Watterson's thetaW. We show that this test is most powerful in
      detecting the recovery phase after the loss of genetic diversity, which includes
      the postselective sweep phase. The sensitivities of these tests to (or robustness
      against) background selection and demographic changes are also considered.
      Overall, D and H in combination can be most effective in detecting positive
      selection while being insensitive to other perturbations. We thus propose a joint
      test, referred to as the DH test. Simulations indicate that DH is indeed
      sensitive primarily to directional selection and no other driving forces.

PMID- 16951062
TI  - High nucleotide polymorphism and rapid decay of linkage disequilibrium in wild
      populations of Caenorhabditis remanei.
AB  - The common ancestor of the self-fertilizing nematodes Caenorhabditis elegans and
      C. briggsae must have reproduced by obligate outcrossing, like most species in
      this genus. However, we have only a limited understanding about how genetic
      variation is patterned in such male-female (gonochoristic) Caenorhabditis
      species. Here, we report results from surveying nucleotide variation of six
      nuclear loci in a broad geographic sample of wild isolates of the gonochoristic
      C. remanei. We find high levels of diversity in this species, with silent-site
      diversity averaging 4.7%, implying an effective population size close to 1
      million. Additionally, the pattern of polymorphisms reveals little evidence for
      population structure or deviation from neutral expectations, suggesting that the
      sampled C. remanei populations approximate panmixis and demographic equilibrium.
      Combined with the observation that linkage disequilibrium between pairs of
      polymorphic sites decays rapidly with distance, this suggests that C. remanei
      will provide an excellent system for identifying the genetic targets of natural
      selection from deviant patterns of polymorphism and linkage disequilibrium. The
      patterns revealed in this obligately outcrossing species may provide a useful
      model of the evolutionary circumstances in C. elegans' gonochoristic progenitor.
      This will be especially important if self-fertilization evolved recently in C.
      elegans history, because most of the evolutionary time separating C. elegans from
      its known relatives would have occurred in a state of obligate outcrossing.

PMID- 16951065
TI  - Can random mutation mimic design?: a guided inquiry laboratory for undergraduate
      students.
AB  - Complex biological structures, such as the human eye, have been interpreted as
      evidence for a creator for over three centuries. This raises the question of
      whether random mutation can create such adaptations. In this article, we present
      an inquiry-based laboratory experiment that explores this question using paper
      airplanes as a model organism. The main task for students in this investigation
      is to figure out how to simulate paper airplane evolution (including
      reproduction, inheritance, mutation, and selection). In addition, the lab
      requires students to practice analytic thinking and to carefully delineate the
      implications of their results.

PMID- 16951064
TI  - Ribosomal DNA in the grasshopper Podisma pedestris: escape from concerted
      evolution.
AB  - Eukaryote nuclear ribosomal DNA (rDNA) typically exhibits strong concerted
      evolution: a pattern in which several hundred rDNA sequences within any one
      species show little or no genetic diversity, whereas the sequences of different
      species diverge. We report a markedly different pattern in the genome of the
      grasshopper Podisma pedestris. Single individuals contain several highly
      divergent ribosomal DNA groups. Analysis of the magnitude of divergence indicates
      that these groups have coexisted in the Podisma lineage for at least 11 million
      years. There are two putatively functional groups, each estimated to be at least
      4 million years old, and several pseudogene groups, many of which are
      transcribed. Southern hybridization and real-time PCR experiments show that only
      one of the putatively functional types occurs at high copy number. However, this
      group is scarcely amplified under standard PCR conditions, which means that
      phylogenetic inference on the basis of standard PCR would be severely distorted.
      The analysis suggests that concerted evolution has been remarkably ineffective in
      P. pedestris. We propose that this outcome may be related to the species'
      exceptionally large genome and the associated low rate of deletion per base pair,
      which may allow pseudogenes to persist.

PMID- 16951066
TI  - Dynamical analysis of the regulatory network defining the dorsal-ventral boundary
      of the Drosophila wing imaginal disc.
AB  - The larval development of the Drosophila melanogaster wings is organized by the
      protein Wingless, which is secreted by cells adjacent to the dorsal-ventral (DV)
      boundary. Two signaling processes acting between the second and early third
      instars and between the mid- and late third instar control the expression of
      Wingless in these boundary cells. Here, we integrate both signaling processes
      into a logical multivalued model encompassing four cells, i.e., a boundary and a
      flanking cell at each side of the boundary. Computer simulations of this model
      enable a qualitative reproduction of the main wild-type and mutant phenotypes
      described in the experimental literature. During the first signaling process,
      Notch becomes activated by the first signaling process in an Apterous-dependent
      manner. In silico perturbation experiments show that this early activation of
      Notch is unstable in the absence of Apterous. However, during the second
      signaling process, the Notch pattern becomes consolidated, and thus independent
      of Apterous, through activation of the paracrine positive feedback circuit of
      Wingless. Consequently, we propose that appropriate delays for Apterous
      inactivation and Wingless induction by Notch are crucial to maintain the wild
      type expression at the dorsal-ventral boundary. Finally, another mutant
      simulation shows that cut expression might be shifted to late larval stages
      because of a potential interference with the early signaling process.

PMID- 16951067
TI  - Trans-kingdom transposition of the maize dissociation element.
AB  - Transposons are very valuable tools for genetic manipulation. However, the number
      of transposable elements that have been suitably adapted for experimental use is
      insufficient and the spectrum of heterologous hosts in which they have been
      deployed is restricted. To date, only transposons from animal hosts have been
      utilized in heterologous animal species and transposons of plant origin have been
      used in plant genetics. There has been no experimental evidence that any of the
      known elements could transpose in hosts belonging to both kingdoms. Here we
      demonstrate that the maize Dissociation (Ds) element is capable of effective
      Activator (Ac) transposase-mediated transposition in the zebrafish Danio rerio,
      yielding remarkable germline transmission rates. In addition, mammalian cells
      were also found to be conducive to Ds transposition. Furthermore, we demonstrate
      that nuclear localization of Ac transposase is essential for genomic Ds
      transposition. Our results support the hypothesis that Ac/Ds elements do not rely
      on host-specific factors for transposition and that host factors involved in
      their mobility mechanism are widely conserved. Finally, even in vertebrate cells,
      the Ac/Ds system displays accurate transposition, large-fragment carrying
      capacity, high transposition frequencies, efficient germline transmission, and
      reporter gene expression, all of which are advantageous for various genetic
      applications and animal biotechnology.

PMID- 16951068
TI  - Comparative genomics of host-specific virulence in Pseudomonas syringae.
AB  - While much study has gone into characterizing virulence factors that play a
      general role in disease, less work has been directed at identifying pathogen
      factors that act in a host-specific manner. Understanding these factors will help
      reveal the variety of mechanisms used by pathogens to suppress or avoid host
      defenses. We identified candidate Pseudomonas syringae host-specific virulence
      genes by searching for genes whose distribution among natural P. syringae
      isolates was statistically associated with hosts of isolation. We analyzed 91
      strains isolated from 39 plant hosts by DNA microarray-based comparative genomic
      hybridization against an array containing 353 virulence-associated (VA) genes,
      including 53 type III secretion system effectors (T3SEs). We identified
      individual genes and gene profiles that were significantly associated with
      strains isolated from cauliflower, Chinese cabbage, soybean, rice, and tomato. We
      also identified specific horizontal gene acquisition events associated with host
      shifts by mapping the array data onto the core genome phylogeny of the species.
      This study provides the largest suite of candidate host-specificity factors from
      any pathogen, suggests that there are multiple ways in which P. syringae isolates
      can adapt to the same host, and provides insight into the evolutionary mechanisms
      underlying host adaptation.

PMID- 16951069
TI  - Using dominance relationship coefficients based on linkage disequilibrium and
      linkage with a general complex pedigree to increase mapping resolution.
AB  - Dominance (intralocus allelic interactions) plays often an important role in
      quantitative trait variation. However, few studies about dominance in QTL mapping
      have been reported in outbred animal or human populations. This is because common
      dominance effects can be predicted mainly for many full sibs, which do not often
      occur in outbred or natural populations with a general pedigree. Moreover,
      incomplete genotypes for such a pedigree make it infeasible to estimate dominance
      relationship coefficients between individuals. In this study, identity-by-descent
      (IBD) coefficients are estimated on the basis of population-wide linkage
      disequilibrium (LD), which makes it possible to track dominance relationships
      between unrelated founders. Therefore, it is possible to use dominance effects in
      QTL mapping without full sibs. Incomplete genotypes with a complex pedigree and
      many markers can be efficiently dealt with by a Markov chain Monte Carlo method
      for estimating IBD and dominance relationship matrices (D(RM)). It is shown by
      simulation that the use of D(RM) increases the likelihood ratio at the true QTL
      position and the mapping accuracy and power with complete dominance,
      overdominance, and recessive inheritance modes when using 200 genotyped and
      phenotyped individuals.

PMID- 16951070
TI  - Perfect simulation from nonneutral population genetic models: variable population
      size and population subdivision.
AB  - We show how the idea of monotone coupling from the past can produce simple
      algorithms for simulating samples at a nonneutral locus under a range of
      demographic models. We specifically consider a biallelic locus and either a
      general variable population size mode or a general migration model for population
      subdivision. We investigate the effect of demography on the efficacy of selection
      and the effect of selection on genetic divergence between populations.

PMID- 16951071
TI  - Misregulation of sex-lethal and disruption of male-specific lethal complex
      localization in Drosophila species hybrids.
AB  - A major model system for the study of evolutionary divergence between closely
      related species has been the unisexual lethality resulting from reciprocal
      crosses of Drosophila melanogaster and D. simulans. Sex-lethal (Sxl), a critical
      gene for sex determination, is misregulated in these hybrids. In hybrid males
      from D. melanogaster mothers, there is an abnormal expression of Sxl and a
      failure of localization of the male-specific lethal (MSL) complex to the X
      chromosome, which causes changes in gene expression. Introduction of a Sxl
      mutation into this hybrid genotype will allow expression of the MSL complex but
      there is no sequestration to the X chromosome. Lethal hybrid rescue (Lhr), which
      allows hybrid males from this cross to survive, corrects the SXL and MSL defects.
      The reciprocal cross of D. simulans mothers by D. melanogaster males exhibits
      underexpression of Sxl in embryos.

PMID- 16951072
TI  - A chip off the old block: a model for the evolution of genomic imprinting via
      selection for parental similarity.
AB  - A consequence of genomic imprinting is that offspring are more similar to one
      parent than to the other, depending on which parent's genes are inactivated in
      those offspring. We hypothesize that genomic imprinting may have evolved at some
      loci because of selection to be similar to the parent of one sex or the other. We
      construct and analyze an evolutionary-genetic model of a two-locus two-deme
      system, in which one locus codes for a character under local selection and the
      second locus is a potential cis-acting modifier of imprinting. A proportion of
      males only migrate between demes every generation, and prebreeding males are less
      fit, on average, than females. We examine the conditions in which an imprinting
      modifier allele can invade a population fixed for a nonimprinting modifier allele
      and vice versa. We find that the conditions under which the imprinting modifier
      invades are biologically restrictive (high migration rates and high values of
      recombination between the two loci) and thus this hypothesis is unlikely to
      explain the evolution of imprinting. Our modeling also shows that, as with
      several other hypotheses, polymorphism of imprinting status may evolve under
      certain circumstances, a feature not predicted by verbal accounts.

PMID- 16951073
TI  - Precise centromere mapping using a combination of repeat junction markers and
      chromatin immunoprecipitation-polymerase chain reaction.
AB  - Centromeres are difficult to map even in species where genetic resolution is
      excellent. Here we show that junctions between repeats provide reliable single
      copy markers for recombinant inbred mapping within centromeres and
      pericentromeric heterochromatin. Repeat junction mapping was combined with anti
      CENH3-mediated ChIP to provide a definitive map position for maize centromere 8.

PMID- 16951074
TI  - Genetic dissection of intermated recombinant inbred lines using a new genetic map
      of maize.
AB  - A new genetic map of maize, ISU-IBM Map4, that integrates 2029 existing markers
      with 1329 new indel polymorphism (IDP) markers has been developed using
      intermated recombinant inbred lines (IRILs) from the intermated B73xMo17 (IBM)
      population. The website http://magi.plantgenomics.iastate.edu provides access to
      IDP primer sequences, sequences from which IDP primers were designed, optimized
      marker-specific PCR conditions, and polymorphism data for all IDP markers. This
      new gene-based genetic map will facilitate a wide variety of genetic and genomic
      research projects, including map-based genome sequencing and gene cloning. The
      mosaic structures of the genomes of 91 IRILs, an important resource for
      identifying and mapping QTL and eQTL, were defined. Analyses of segregation data
      associated with markers genotyped in three B73/Mo17-derived mapping populations
      (F2, Syn5, and IBM) demonstrate that allele frequencies were significantly
      altered during the development of the IBM IRILs. The observations that two
      segregation distortion regions overlap with maize flowering-time QTL suggest that
      the altered allele frequencies were a consequence of inadvertent selection.
      Detection of two-locus gamete disequilibrium provides another means to extract
      functional genomic data from well-characterized plant RILs.

PMID- 16951075
TI  - Unique classes of mutations in the Saccharomyces cerevisiae G-protein translation
      elongation factor 1A suppress the requirement for guanine nucleotide exchange.
AB  - G-proteins play critical roles in many cellular processes and are regulated by
      accessory proteins that modulate the nucleotide-bound state. Such proteins,
      including eukaryotic translation elongation factor 1A (eEF1A), are frequently
      reactivated by guanine nucleotide exchange factors (GEFs). In the yeast
      Saccharomyces cerevisiae, only the catalytic subunit of the GEF complex,
      eEF1Balpha, is essential for viability. The requirement for the TEF5 gene
      encoding eEF1Balpha can be suppressed by the presence of excess substrate, eEF1A.
      These cells, however, have defects in growth and translation. Two independent
      unbiased screens performed to dissect the cause of these phenotypes yielded
      dominant suppressors that bypass the requirement for extra eEF1A. Surprisingly,
      all mutations are in the G-protein eEF1A and cluster in its GTP-binding domain.
      Five mutants were used to construct novel strains expressing only the eEF1A
      mutant at normal levels. These strains show no growth defects and little to no
      decreases in total translation, which raises questions as to the evolutionary
      expression of GEF complexity and other potential functions of this complex. The
      location of the mutations on the eEF1A-eEF1Balpha structure suggests that their
      mechanism of suppression may depend on effects on the conserved G-protein
      elements: the P-loop and NKXD nucleotide-binding element.

PMID- 16951076
TI  - Complex genetic architecture revealed by analysis of high-density lipoprotein
      cholesterol in chromosome substitution strains and F2 crosses.
AB  - Intercrosses between inbred lines provide a traditional approach to analysis of
      polygenic inheritance in model organisms. Chromosome substitution strains (CSSs)
      have been developed as an alternative to accelerate the pace of gene
      identification in quantitative trait mapping. We compared a classical intercross
      and three CSS intercrosses to examine the genetic architecture underlying plasma
      high-density lipoprotein cholesterol (HDL) levels in the C57BL/6J (B) and A/J (A)
      mouse strains. The B x A intercross revealed significant quantitative trait loci
      (QTL) for HDL on chromosomes 1, 4, 8, 15, 17, 18, and 19. A CSS survey revealed
      that many have significantly different HDL levels compared to the background
      strain B, including chromosomes with no significant QTL in the intercross and, in
      some cases (CSS-1, CSS-17), effects that are opposite to those observed in the B
      x A intercross population. Intercrosses between B and three CSSs (CSS-3, CSS-11,
      and CSS-8) revealed significant QTL but with some unexpected differences from the
      B x A intercross. Our inability to predict the results of CSS intercrosses
      suggests that additional complexity will be revealed by further crosses and that
      the CSS mapping strategy should be viewed as a complement to, rather than a
      replacement for, classical intercross mapping.

PMID- 16951078
TI  - Identifying the environmental factors that determine the genetic structure of
      populations.
AB  - The study of population genetic structure is a fundamental problem in population
      biology because it helps us obtain a deeper understanding of the evolutionary
      process. One of the issues most assiduously studied in this context is the
      assessment of the relative importance of environmental factors (geographic
      distance, language, temperature, altitude, etc.) on the genetic structure of
      populations. The most widely used method to address this question is the
      multivariate Mantel test, a nonparametric method that calculates a correlation
      coefficient between a dependent matrix of pairwise population genetic distances
      and one or more independent matrices of environmental differences. Here we
      present a hierarchical Bayesian method that estimates F(ST) values for each local
      population and relates them to environmental factors using a generalized linear
      model. The method is demonstrated by applying it to two data sets, a data set for
      a population of the argan tree and a human data set comprising 51 populations
      distributed worldwide. We also carry out a simulation study to investigate the
      performance of the method and find that it can correctly identify the factors
      that play a role in the structuring of genetic diversity under a wide range of
      scenarios.

PMID- 16951077
TI  - A polymorphism in the 5'-untranslated region of the porcine cholecystokinin type
      a receptor gene affects feed intake and growth.
AB  - The location and utilization of quantitative trait loci (QTL) and candidate genes
      with significant effects on economically important traits are becoming
      increasingly important in livestock breeding programs. The porcine
      cholecystokinin type A receptor (CCKAR) is a candidate gene for performance
      traits, due to its known role in the physiological control of feed intake,
      satiety, and obesity. We investigated the association of CCKAR polymorphisms with
      feeding, growth, and efficiency traits in an F2 population derived from a cross
      between Meishan and Large White founder animals and in lines of Large White pigs
      that had been divergently selected on the basis of lean growth efficiency traits.
      In the F2 population, CCKAR genotype was significantly associated with daily feed
      intake and average daily gain. The effects of the polymorphisms were then
      assessed in a larger-scale analysis of segregating commercial lines. A newly
      discovered single-nucleotide polymorphism (SNP) within the 5'-untranslated region
      (5'-UTR) had highly significant effects on feed intake, average daily gain, and
      days to 110 kg, which were not seen for a previously reported SNP within the
      CCKAR gene. Furthermore, we provide evidence that the novel SNP disrupts the
      binding of the YY1 transcription factor, which raises the possibility that it is
      the causal variant. The 5'-UTR SNP could be utilized as a molecular genetic test
      for increased feed intake, faster lean growth, and reduced days to market weight
      in segregating commercial lines.

PMID- 16951079
TI  - Amh and Dmrta2 genes map to tilapia (Oreochromis spp.) linkage group 23 within
      quantitative trait locus regions for sex determination.
AB  - Recent studies have revealed that the major genes of the mammalian sex
      determination pathway are also involved in sex determination of fish. Several
      studies have reported QTL in various species and strains of tilapia, regions
      contributing to sex determination have been identified on linkage groups 1, 3,
      and 23. Genes contributing to sex-specific mortality have been detected on
      linkage groups 2, 6, and 23. To test whether the same genes might control sex
      determination in mammals and fishes, we mapped 11 genes that are considered
      putative master key regulators of sex determination: Amh, Cyp19, Dax1, Dmrt2,
      Dmrta2, Fhl3l, Foxl2, Ixl, Lhx9, Sf1, and Sox8. We identified polymorphisms in
      noncoding regions of these genes and genotyped these sites for 90 individuals of
      an F2 mapping family. Mapping of Dax1 joined LG16 and LG21 into a single linkage
      group. The Amh and Dmrta2 genes were mapped to two distinct regions of LG23. The
      Amh gene was mapped 5 cM from UNH879 within a QTL region for sex determination
      and 2 cM from UNH216 within a QTL region for sex-specific mortality. Dmrta2 was
      mapped 4 cM from UNH848 within another QTL region for sex determination. Cyp19
      was mapped to LG1 far from a previously reported QTL region for sex determination
      on this chromosome. Seven other candidate genes mapped to LG4, -11, -12, -14, and
      -17.

PMID- 16951080
TI  - A genetic linkage map of the hermaphrodite teleost fish Sparus aurata L.
AB  - The gilthead sea bream (Sparus aurata L.) is a marine fish of great importance
      for fisheries and aquaculture. It has also a peculiar sex-determination system,
      being a protandrous hermaphrodite. Here we report the construction of a first
      generation genetic linkage map for S. aurata, based on 204 microsatellite
      markers. Twenty-six linkage groups (LG) were found. The total map length was
      1241.9 cM. The ratio between sex-specific map lengths was 1:1.2 (male:female).
      Comparison with a preliminary radiation hybrid (RH) map reveals a good
      concordance, as all markers located in a single LG are located in a single RH
      group, except for Ad-25 and CId-31. Comparison with the Tetraodon nigroviridis
      genome revealed a considerable number of evolutionary conserved regions (ECRs)
      between the two species. The mean size of ECRs was 182 bp (sequence identity 60
      90%). Forty-one ECRs have a known chromosomal location in the pufferfish genome.
      Despite the limited number of anchoring points, significant syntenic
      relationships were found. The linkage map presented here provides a robust
      comparative framework for QTL analysis in S. aurata and is a step toward the
      identification of genetic loci involved both in the determination of economically
      important traits and in the individual timing of sex reversal.

PMID- 16951081
TI  - Mutator phenotype of Caenorhabditis elegans DNA damage checkpoint mutants.
AB  - DNA damage response proteins identify sites of DNA damage and signal to
      downstream effectors that orchestrate either apoptosis or arrest of the cell
      cycle and DNA repair. The C. elegans DNA damage response mutants mrt-2, hus-1,
      and clk-2(mn159) displayed 8- to 15-fold increases in the frequency of
      spontaneous mutation in their germlines. Many of these mutations were small- to
      medium-sized deletions, some of which had unusual sequences at their breakpoints
      such as purine-rich tracts or direct or inverted repeats. Although DNA-damage
      induced apoptosis is abrogated in the mrt-2, hus-1, and clk-2 mutant backgrounds,
      lack of the apoptotic branch of the DNA damage response pathway in cep-1/p53, ced
      3, and ced-4 mutants did not result in a Mutator phenotype. Thus, DNA damage
      checkpoint proteins suppress the frequency of mutation by ensuring that
      spontaneous DNA damage is accurately repaired in C. elegans germ cells. Although
      DNA damage response defects that predispose humans to cancer are known to result
      in large-scale chromosome aberrations, our results suggest that small- to medium
      sized deletions may also play roles in the development of cancer.

PMID- 16951083
TI  - Natural isolates of Saccharomyces cerevisiae display complex genetic variation in
      sporulation efficiency.
AB  - Sporulation is a well-studied process executed with varying efficiency by diverse
      yeast strains. We developed a high-throughput method to quantify yeast
      sporulation efficiency and used this technique to analyze a line cross between a
      high-efficiency oak tree isolate and a low-efficiency wine strain. We find that
      natural variation in sporulation efficiency mirrors natural variation in higher
      eukaryotes: it shows divergence between isolated populations, arises from loci of
      major effect, and exhibits epistasis. We show that the lower sporulation
      efficiency of the wine strain results from a failure to initiate sporulation,
      rather than from slower kinetics of meiosis and spore formation. The two strains
      differentially regulate many genes involved in aerobic respiration, an essential
      pathway for sporulation, such that the oak tree strain appears better poised to
      generate energy from this pathway. We also report that a polymorphism in RME1
      that affects sporulation efficiency in laboratory strains also cosegregates with
      significant phenotypic differences in our cross of natural isolates. These
      results lay the groundwork for the study of variation in sporulation efficiency
      among natural isolates of yeast.

PMID- 16951085
TI  - Assignment of rainbow trout linkage groups to specific chromosomes.
AB  - The rainbow trout genetic linkage groups have been assigned to specific
      chromosomes in the OSU (2N=60) strain using fluorescence in situ hybridization
      (FISH) with BAC probes containing genes mapped to each linkage group. There was a
      rough correlation between chromosome size and size of the genetic linkage map in
      centimorgans for the genetic maps based on recombination from the female parent.
      Chromosome size and structure have a major impact on the female:male
      recombination ratio, which is much higher (up to 10:1 near the centromeres) on
      the larger metacentric chromosomes compared to smaller acrocentric chromosomes.
      Eighty percent of the BAC clones containing duplicate genes mapped to a single
      chromosomal location, suggesting that diploidization resulted in substantial
      divergence of intergenic regions. The BAC clones that hybridized to both
      duplicate loci were usually located in the distal portion of the chromosome.
      Duplicate genes were almost always found at a similar location on the chromosome
      arm of two different chromosome pairs, suggesting that most of the chromosome
      rearrangements following tetraploidization were centric fusions and did not
      involve homeologous chromosomes. The set of BACs compiled for this research will
      be especially useful in construction of genome maps and identification of QTL for
      important traits in other salmonid fishes.

PMID- 16951086
TI  - Isochores exhibit evidence of genes interacting with the large-scale genomic
      environment.
AB  - The genomes of mammals and birds can be partitioned into megabase-long regions,
      termed isochores, with consistently high, or low, average C + G content.
      Isochores with high CG contain a mixture of CG-rich and AT-rich genes, while high
      AT isochores contain predominantly AT-rich genes. The two gene populations in the
      high-CG isochores are functionally distinguishable by statistical analysis of
      their gene ontology categories. However, the aggregate of the two populations in
      CG isochores is not statistically distinct from AT-rich genes in AT isochores.
      Genes tend to be located at local extrema of composition within the isochores,
      indicating that the CG-enriching mechanism acted differently when near to genes.
      On the other hand, maximum-likelihood reconstruction of molecular phylogenetic
      trees shows that branch lengths (evolutionary distances) for third codon
      positions in CG-rich genes are not substantially larger than those for AT-rich
      genes. In the context of neutral mutation theory this argues against any strong
      positive selection. Disparate features of isochores might be explained by a model
      in which about half of all genes functionally require AT richness, while, in warm
      blooded organisms, about half the genome (in large coherent blocks) acquired a
      strong bias for mutations to CG. Using mutations in CG-rich genes as convenient
      indicators, we show that approximately 20% of amino acids in proteins are broadly
      substitutable, without regard to chemical similarity.

PMID- 16951082
TI  - History and structure of sub-Saharan populations of Drosophila melanogaster.
AB  - Drosophila melanogaster is an important model organism in evolutionary genetics,
      yet little is known about the population structure and the demographic history of
      this species within sub-Saharan Africa, which is thought to contain its ancestral
      range. We surveyed nucleotide variation at four 1-kb fragments in 240 individual
      lines representing 21 sub-Saharan and 4 Palearctic population samples of D.
      melanogaster. In agreement with recent studies, we find a small but significant
      level of genetic differentiation within sub-Saharan Africa. A clear geographic
      pattern is observed, with eastern and western African populations composing two
      genetically distinct groups. This pattern may have resulted from a relatively
      recent establishment of D. melanogaster in western Africa. Eastern populations
      show greater evidence for long-term stability, consistent with the hypothesis
      that eastern Africa contains the ancestral range of the species. Three sub
      Saharan populations show evidence for cosmopolitan introgression. Apart from
      those cases, the closest relationships between Palearctic and sub-Saharan
      populations involve a sample from the rift zone (Uganda), suggesting that the
      progenitors of Palearctic D. melanogaster might have come from this region.
      Finally, we find a large excess of singleton polymorphisms in the full data set,
      which is best explained by a combination of population growth and purifying
      selection.

PMID- 16951089
TI  - Arthroscopic osseous Bankart repair for chronic recurrent traumatic anterior
      glenohumeral instability. Surgical technique.
AB  - BACKGROUND: A chronic osseous Bankart lesion has traditionally been treated with
      soft-tissue repair and/or open bone-grafting for a large glenoid defect. We
      developed an arthroscopic method of osseous reconstruction of the glenoid without
      bone-grafting. The purpose of this study was to evaluate the postoperative
      outcomes of our technique for chronic recurrent traumatic anterior glenohumeral
      instability. METHODS: A consecutive series of forty-two shoulders in forty-one
      patients with chronic recurrent traumatic glenohumeral instability underwent an
      arthroscopic osseous Bankart repair. All shoulders were evaluated preoperatively
      with three-dimensionally reconstructed computed tomography, which confirmed an
      osseous fragment at the anteroinferior portion of the glenoid. The average bone
      loss in the glenoid was 24.8% (range, 11.4% to 38.6%), and the average fragment
      size was 9.2% (range, 2.1% to 20.9%) of the glenoid fossa. In all shoulders, a
      displaced osseous fragment, firmly attached to the labroligamentous complex, was
      separated from the glenoid neck before reduction and fixation in the optimal
      position with use of suture anchors. All patients were assessed with use of the
      scoring systems of Rowe et al. and the University of California at Los Angeles
      preoperatively and at the final evaluation. RESULTS: The mean duration of follow
      up was thirty-four months. At that time, thirty-nine of the forty-two shoulders
      were rated as having a good or excellent result. The mean Rowe score improved
      from 33.6 points preoperatively to 94.3 points postoperatively (p < 0.01). The
      mean score on the University of California at Los Angeles system improved from
      20.5 points preoperatively to 33.6 points at the final evaluation (p < 0.01). The
      average passive external rotation was 75 degrees with the arm at the side and 93
      degrees with the arm at 90 degrees of abduction. Two patients had a reinjury.
      Eventually, thirty-five of thirty-seven patients who were active participants in
      sports returned to the sport they had played before the injury. CONCLUSIONS:
      Arthroscopic osseous Bankart repair with use of suture anchors yields a
      successful outcome even in shoulders with a chronic large glenoid defect.

PMID- 16951088
TI  - Chromatin-modifiying enzymes are essential when the Saccharomyces cerevisiae
      morphogenesis checkpoint is constitutively activated.
AB  - Hsl7p plays a central role in the morphogenesis checkpoint triggered when yeast
      bud formation is impaired and is proposed to function as an arginine
      methyltransferase. HSL7 is also essential in the absence of the N-terminal tails
      of histones H3 or H4. The requirement for H3 and H4 tails may indicate a need for
      their post-translational modification to bypass the morphogenesis checkpoint. In
      support of this, the absence of the acetyltransferases Gcn5p or Esa1p, the
      deacetylase Rpd3p, or the lysine-methyltransferase Set1p resulted in death or
      extreme sickness in hslDelta mutants. These synthetic interactions involved both
      the activity of the chromatin-modifying enzymes and the complexes through which
      they act. Newly reported silencing phenotypes of hsl7Delta mirror those
      previously reported for gcn5Delta and rpd3Delta, thereby strengthening their
      functional links. In addition, synthetic interactions and silencing phenotypes
      were suppressed by inactivation of the morphogenesis checkpoint, either by SWE1
      deletion or by preventing Cdc28p phosphorylation. A catalytically dead Hsl7p
      retained wild-type interactions, implying that modification of histone H3 or H4 N
      termini by Gcn5p, Esa1p, Rpd3p, and Set1p, but not by Hsl7p, was needed to bypass
      the morphogenesis checkpoint.

PMID- 16951084
TI  - Widespread adaptive evolution of Drosophila genes with sex-biased expression.
AB  - Many genes in higher eukaryotes show sexually dimorphic expression, and these
      genes tend to be among the most divergent between species. In most cases,
      however, it is not known whether this rapid divergence is caused by positive
      selection or if it is due to a relaxation of selective constraint. To distinguish
      between these two possibilities, we surveyed DNA sequence polymorphism in 91
      Drosophila melanogaster genes with male-, female-, or nonsex-biased expression
      and determined their divergence from the sister species D. simulans. Using
      several single- and multilocus statistical tests, we estimated the type and
      strength of selection influencing the evolution of the proteins encoded by genes
      of each expression class. Adaptive evolution, as indicated by a relative excess
      of nonsynonymous divergence between species, was common among the sex-biased
      genes (both male and female). Male-biased genes, in particular, showed a strong
      and consistent signal of positive selection, while female-biased genes showed
      more variation in the type of selection they experience. Genes expressed equally
      in the two sexes, in contrast, showed no evidence for adaptive evolution between
      D. melanogaster and D. simulans. This suggests that sexual selection and
      intersexual coevolution are the major forces driving genetic differentiation
      between species.

PMID- 16951090
TI  - Lesser tuberosity osteotomy for total shoulder arthroplasty. Surgical technique.
AB  - BACKGROUND: Recent studies have suggested that tenotomy and repair of the
      subscapularis tendon carried out for anterior approaches to the shoulder can be
      followed by failure of the tendon repair and by changes resulting in permanent
      loss of subscapularis function. We hypothesized that release of the subscapularis
      with use of a superficial osteotomy of the lesser tuberosity followed by repair
      of the two opposing bone surfaces would lead to consistent bone-to-bone healing,
      which would be possible to monitor radiographically, and would lead to
      satisfactory clinical and structural outcomes. METHODS: Thirty-nine shoulders in
      thirty-six consecutive patients who, at an average age of fifty-seven years, had
      undergone total shoulder replacement through an anterior approach involving an
      osteotomy of the lesser tuberosity were evaluated at an average of thirty-nine
      months. Assessment included a standardized interview and physical examination,
      scoring according to the system described by Constant and Murley, and imaging
      with conventional radiography and computed tomography to assess healing of the
      osteotomy site and changes in the subscapularis. RESULTS: The osteotomized
      tuberosity fragment healed in an anatomical position in all shoulders, and no
      cuff tendon ruptures were observed. At the time of follow-up, thirty-three (89%)
      of thirty-seven shoulders evaluated with a belly-press test had a negative result
      and twenty-seven (75%) of thirty-six shoulders evaluated with a lift-off test had
      an unequivocally normal result. Fatty infiltration of the subscapularis muscle
      increased after the operation (p < 0.0001) and was at least stage two in eleven
      (32%) of thirty-four shoulders. The fatty infiltration had progressed by one
      stage in eight (24%) of the thirty-four shoulders, by two stages in five
      shoulders (15%), and by three stages in two shoulders (6%). CONCLUSIONS:
      Osteotomy of the lesser tuberosity provides an easy anterior approach for total
      shoulder replacement and is followed by consistent bone-to-bone healing, which
      can be monitored, and good subscapularis function. In the presence of documented
      anatomical healing of the osteotomy site, postoperative fatty infiltration of the
      subscapularis muscle remains unexplained and needs to be investigated further as
      it is associated with a poorer clinical outcome.

PMID- 16951092
TI  - Supracondylar dome osteotomy for cubitus valgus deformity associated with a
      lateral condylar nonunion in children. Surgical technique.
AB  - BACKGROUND: Open reduction, autogenous bone-grafting, and internal fixation for
      the treatment of established nonunion of the lateral condyle associated with a
      cubitus valgus deformity has a high rate of complications. As a consequence, we
      developed a new technique that includes in situ compression fixation of the
      lateral condylar nonunion and a dome-shaped supracondylar osteotomy of the distal
      aspect of the humerus through a single posterior incision. METHODS: Eight
      consecutive patients were treated with the new surgical technique between 1994
      and 2000. The mean age at the time of surgery was 8.6 years. The mean interval
      between the lateral condylar fracture and surgery was 4.9 years. The mean
      preoperative radiographic humerus-ulna angle was 31 degrees of valgus. The
      postoperative results were classified with a modification of the scoring system
      described by Dhillon et al., which assesses pain, weakness, range of motion, the
      humerus-ulna angle, and prominence of the medial epicondyle on a 12-point scale.
      RESULTS: All eight lateral condylar nonunions achieved union within three months
      postoperatively. The mean postoperative humerus-ulna angle was 5.5 degrees of
      valgus. All of the supracondylar dome osteotomies healed uneventfully, and there
      was no loss of correction postoperatively. The mean duration of follow-up was 4.5
      years. The overall results were excellent in two patients, good in four patients,
      and fair in two patients. CONCLUSIONS: With better exposure of the lateral
      condylar nonunion through a posterior approach, we can effectively stabilize the
      lateral condylar nonunion and avoid postoperative loss of motion and
      osteonecrosis of the condyle. With a dome-shaped supracondylar osteotomy, we can
      correct the cubitus valgus deformity and avoid the development of a medial
      epicondylar prominence. With careful selection of patients, this new technique
      can be an effective method to treat this clinically challenging problem.

PMID- 16951091
TI  - The reverse shoulder prosthesis for glenohumeral arthritis associated with severe
      rotator cuff deficiency. a minimum two-year follow-up study of sixty patients
      surgical technique.
AB  - BACKGROUND: Patients who have pain and dysfunction from glenohumeral arthritis
      associated with severe rotator cuff deficiency have few treatment options. The
      goal of this study was to retrospectively evaluate the short-term results of
      arthroplasty with use of the Reverse Shoulder Prosthesis in the management of
      this problem. METHODS: We report the results for sixty patients (sixty shoulders)
      with a rotator cuff deficiency and glenohumeral arthritis who were followed for a
      minimum of two years. Thirty-five patients had no previous shoulder surgery,
      whereas twenty-three had had either an open or arthroscopic rotator cuff repair,
      one had had a subacromial decompression, and one had had a biceps tendon repair.
      All patients were assessed preoperatively and postoperatively with the American
      Shoulder and Elbow Surgeons scoring system for pain and function and with visual
      analog scales for pain and function. They were also asked to rate their
      satisfaction with the outcome. The shoulder range of motion was measured
      preoperatively and postoperatively. RESULTS: The average age of the patients was
      seventy-one years. The average duration of follow-up was thirty-three months. All
      measures improved significantly (p < 0.0001). The mean total score on the
      American Shoulder and Elbow Surgeons system improved from 34.3 to 68.2; the mean
      function score, from 16.1 to 29.4; and the mean pain score, from 18.2 to 38.7.
      The score for function on the visual analog scale improved from 2.7 to 6.0, and
      the score for pain on the visual analog scale improved from 6.3 to 2.2. Forward
      flexion increased from 55.0 degrees to 105.1 degrees , and abduction increased
      from 41.4 degrees to 101.8 degrees . Forty-one of the sixty patients rated the
      outcome as good or excellent; sixteen were satisfied, and three were
      dissatisfied. There were a total of thirteen complications in ten patients (17%).
      Seven patients (12%) had eight failures, requiring revision surgery to another
      Reverse Shoulder Prosthesis in five patients (one shoulder had two revisions) and
      revision to a hemiarthroplasty in two patients because of deep infection.
      CONCLUSIONS: The data from this study suggest that arthroplasty with the Reverse
      Shoulder Prosthesis may be a viable treatment for patients with glenohumeral
      arthritis and a massive rotator cuff tear. However, future studies will be
      necessary to determine the longevity of the implant and whether it will provide
      continued improvement in function.

PMID- 16951087
TI  - Evolution of the human immunodeficiency virus envelope gene is dominated by
      purifying selection.
AB  - The evolution of the human immunodeficiency virus (HIV-1) during chronic
      infection involves the rapid, continuous turnover of genetic diversity. However,
      the role of natural selection, relative to random genetic drift, in governing
      this process is unclear. We tested a stochastic model of genetic drift using
      partial envelope sequences sampled longitudinally in 28 infected children. In
      each case the Bayesian posterior (empirical) distribution of coalescent
      genealogies was estimated using Markov chain Monte Carlo methods. Posterior
      predictive simulation was then used to generate a null distribution of
      genealogies assuming neutrality, with the null and empirical distributions
      compared using four genealogy-based summary statistics sensitive to nonneutral
      evolution. Because both null and empirical distributions were generated within a
      coalescent framework, we were able to explicitly account for the confounding
      influence of demography. From the distribution of corrected P-values across
      patients, we conclude that empirical genealogies are more asymmetric than
      expected if evolution is driven by mutation and genetic drift only, with an
      excess of low-frequency polymorphisms in the population. This indicates that
      although drift may still play an important role, natural selection has a strong
      influence on the evolution of HIV-1 envelope. A negative relationship between
      effective population size and substitution rate indicates that as the efficacy of
      selection increases, a smaller proportion of mutations approach fixation in the
      population. This suggests the presence of deleterious mutations. We therefore
      conclude that intrahost HIV-1 evolution in envelope is dominated by purifying
      selection against low-frequency deleterious mutations that do not reach fixation.

PMID- 16951093
TI  - Corrective osteotomy for intra-articular malunion of the distal part of the
      radius. Surgical technique.
AB  - BACKGROUND: Corrective osteotomy is an appealing treatment for malunited
      articular fractures of the distal part of the radius since articular incongruity
      may be the factor most strongly associated with arthrosis and diminished function
      after such fractures. Enthusiasm for osteotomy has been limited by concerns
      regarding the difficulty of the technique and the potential for additional
      injury, osteonecrosis, and nonunion. METHODS: Twenty-three skeletally mature
      patients were evaluated at an average of thirty-eight months after corrective
      osteotomy for an intra-articular malunion of the distal part of the radius. The
      indication for the osteotomy included dorsal or volar subluxation of the
      radiocarpal joint in fourteen patients and articular incongruity of >/=2 mm as
      measured on a posteroanterior radiograph in seventeen patients. Six patients had
      combined intra-articular and extra-articular malunion. The average interval from
      the injury to the osteotomy was six months. The average maximum step-off or gap
      of the articular surface prior to the operation was 4 mm. RESULTS: One patient
      had a subsequent partial wrist arthrodesis because of radiocarpal arthrosis, and
      three patients had additional surgery because of dysfunction of the distal
      radioulnar joint. One patient had a rupture of the extensor pollicis longus,
      which was treated with a tendon transfer. The final articular incongruity
      averaged 0.4 mm, and the final grip strength averaged 85% of that on the
      contralateral side. The rate of excellent or good results was 83% according to
      the rating systems of Fernandez and of Gartland and Werley, and 43% according to
      a modification of the rating system of Green and O'Brien. CONCLUSIONS: The
      results of corrective osteotomy for the treatment of intraarticular malunion are
      comparable with those of osteotomy for the treatment of extra-articular malunion.
      Intra-articular osteotomy can be performed with acceptable safety and efficacy,
      it improves wrist function, and it may help to limit the need for salvage
      procedures such as partial or total wrist arthrodesis.

PMID- 16951094
TI  - Ulnar shortening osteotomy in idiopathic ulnar impaction syndrome. Surgical
      technique.
AB  - BACKGROUND: Idiopathic ulnar impaction syndrome can be defined as a degenerative
      condition of the ulnar aspect of the wrist in patients with congenital or dynamic
      positive ulnar variance without a history of fracture or premature physeal
      arrest. The purpose of this study was to evaluate the clinical features of
      idiopathic ulnar impaction syndrome and the outcomes of ulnar shortening
      osteotomy for this group of patients. METHODS: Thirty-one wrists in twenty-nine
      patients with idiopathic ulnar impaction syndrome were treated with an ulnar
      shortening osteotomy. Ulnar variance was measured on an anteroposterior
      radiograph of the wrist, and radioulnar distance was measured on a lateral
      radiograph, with the forearm in neutral rotation, to evaluate any displacement of
      the ulnar head from the distal aspect of the radius. All patients were followed
      clinically and radiographically for a mean of thirty-two months. RESULTS: An
      average preoperative ulnar variance of +4.6 mm (range, 2 to 7.5 mm) was reduced
      to an average of -0.7 mm (range, -4 to +1 mm) postoperatively. Preoperatively,
      the modified Gartland and Werley score was an average (and standard deviation) of
      69.5 +/- 7.6, with twenty-four wrists rated poor and seven rated fair.
      Postoperatively, the score improved to an average of 92.5 +/- 8.0, with twenty
      four wrists rated excellent; five, good; one, fair; and one, poor. Dorsal
      subluxation of the distal aspect of the ulna was found concomitantly in nine
      wrists, and it was found to be reduced by the shortening osteotomy. Seven
      patients had cystic changes in the carpal bones preoperatively, but these were
      not evident one to two years after the operation. CONCLUSIONS: Ulnar shortening
      osteotomy improved wrist function in patients with idiopathic ulnar impaction
      syndrome and reduced the subluxation of the distal radioulnar joint, which is
      commonly found in these patients. Degenerative cystic changes of the ulnar carpal
      bones appear to resolve following the shortening osteotomy.

PMID- 16951095
TI  - Early complications of primary total hip replacement performed with a two
      incision minimally invasive technique. Surgical technique.
AB  - BACKGROUND: Total hip replacement performed through a small incision
      theoretically results in less trauma to the underlying structures, reduced blood
      loss, less pain, and a shorter hospital stay, but it may result in increased
      complications, particularly early in a surgeon's experience with a new technique.
      In the present study, we reviewed the early results of two techniques involving
      the use of smaller incisions; specifically, we evaluated one series of primary
      total hip replacements that had been performed through two small incisions and
      another series of total hip replacements that had been performed through a single
      small incision. METHODS: Eighty-nine consecutive primary total hip replacements
      were performed with use of the two-incision technique as described by Mears and
      Berger; all procedures were performed without cement and with use of fluoroscopic
      guidance. Outcomes data were reviewed at a minimum of six months following the
      procedure. The results of these procedures were retrospectively compared with
      those of a historical control series of ninety-six total hip replacements that
      had been performed by the same surgeon with use of a single miniincision
      technique. No special attempt was made to discharge any patient early from the
      hospital. In preparation for the use of the two-incision technique, the surgeon
      attended a two-day seminar that included cadaveric training and mentoring by
      surgeons who had experience with this technique. RESULTS: In the two-incision
      group, nine patients (nine hips; 10%) required repeat surgery because of a
      femoral fracture that had been identified postoperatively (two hips), dislocation
      (one hip), a wound complication (two hips), or subsidence and loosening of the
      femoral implant (four hips). Twenty-two patients (twenty-two hips; 25%) sustained
      an injury of the lateral femoral cutaneous nerve, and one patient (one hip) had a
      neuropraxia of the femoral nerve. In the comparative series of ninety-six total
      hip arthroplasties that had been performed with use of a single mini-incision and
      a direct lateral exposure of the hip joint, the overall complication rate was 6%
      (six of ninety-six) and the reoperation rate was 3% (three of ninety-six). The
      rate of complications associated with the two-incision technique decreased
      significantly as the surgeon gained experience with the procedure (p = 0.0202).
      CONCLUSIONS: Although total hip arthroplasty with use of the two-incision
      technique was performed by a surgeon who was experienced in the performance of
      total hip replacement surgery with use of a single small incision, the rates of
      complications and repeat surgery associated with the two-incision technique
      initially were very high. While the rate diminished with increasing experience,
      total hip replacement with use of two incisions and fluoroscopic guidance is a
      technically demanding procedure that may be associated, especially initially,
      with higher rates of complications and repeat surgery.

PMID- 16951096
TI  - Metal-on-metal hybrid surface arthroplasty. Surgical Technique.
AB  - BACKGROUND: Following the reintroduction of metal-on-metal articulating surfaces
      for total hip arthroplasty in Europe in 1988, we developed a surface arthroplasty
      prosthetic system using a metal-on-metal articulation. The present study
      describes the clinical and radiographic results of the first 400 hips treated
      with metal-on-metal hybrid surface arthroplasties at an average follow-up of
      three and a half years. METHODS: Between November 1996 and November 2000, 400
      metal-on-metal hybrid surface arthroplasties were performed in 355 patients. All
      femoral head components were cemented, but only fifty-nine of the short
      metaphyseal stems were cemented. The patients had an average age of forty-eight
      years, 73% were men, and 66% had a diagnosis of osteoarthritis. Clinical and
      radiographic follow-up was performed at three months postoperatively and yearly
      thereafter. RESULTS: The majority of the patients returned to a high level of
      activity, including sports, and 54% had activity scores of >7 on the University
      of California at Los Angeles activity assessment system. Kaplan-Meier
      survivorship curves demonstrated that the rate of survival of the components at
      four years was 94.4%. For patients with a surface arthroplasty risk index score
      of >3, the rate of survival of the components at four years was 89% compared with
      a rate of 97% for those with a score of <or=3. The patients with a higher risk
      index were 4.2 times more likely to undergo revision to a total hip replacement
      at four years. Twelve hips (3%) had a revision to a total hip replacement. Seven
      of the twelve hips were revised because of loosening of the femoral component,
      and three were revised because of a femoral neck fracture. Substantial
      radiolucencies were seen around sixteen uncemented metaphyseal femoral stems. No
      femoral radiolucencies were observed among the hips in which the metaphyseal stem
      was cemented. The most important risk factors for femoral component loosening and
      substantial stem radiolucencies were large femoral head cysts (p = 0.029),
      patient height (p = 0.032), female gender (p = 0.005), and smaller component size
      in male patients (p = 0.005). CONCLUSIONS: The preliminary experience with this
      hybrid metal-on-metal bearing is encouraging. Optimal femoral bone preparation
      and component fixation are critical to improving durability. The metal-on-metal
      hybrid surface arthroplasty is easily revised to a standard femoral component if
      necessary.

PMID- 16951097
TI  - Surgical treatment of fractures of the greater trochanter associated with
      osteolytic lesions. Surgical technique.
AB  - BACKGROUND: A fracture of the greater trochanter through an osteolytic lesion may
      occur as a late complication after total hip arthroplasty. The optimal treatment
      for this difficult complication remains controversial. We have treated this
      problem with internal fixation and allogeneic bone-grafting at the time of
      revision of a loose acetabular component. METHODS: We retrospectively reviewed
      the results of treatment of a fracture through an osteolytic lesion of the
      greater trochanter in nineteen patients seen from 1996 to 2002. All fractures
      were treated with morselized allogeneic bone grafts and wire fixation at the time
      of revision of a failed acetabular component. Postoperative care included the use
      of an abduction orthosis and protected weight-bearing for at least three months.
      Follow-up of all patients consisted of radiographic examinations and clinical
      evaluation with use of the Harris hip score. RESULTS: At an average duration of
      3.8 years after the revision, eighteen of the nineteen fractures had healed. The
      average time to healing was five months. The one treatment failure occurred in a
      patient who did not comply with the use of an abduction orthosis. The average
      Harris hip score for all patients improved from 32.5 points preoperatively to
      91.2 points at the time of the latest follow-up. Polyethylene wear and recurrent
      osteolysis of the greater trochanter was noted in one hip at the eight-year
      follow-up examination. CONCLUSIONS: Fractures of the greater trochanter
      associated with osteolytic lesions can be effectively treated with open
      reduction, internal fixation with wire, and allogeneic bone-grafting.

PMID- 16951098
TI  - Femoral component revision with use of impaction bone-grafting and a cemented
      polished stem. Surgical technique.
AB  - BACKGROUND: The purpose of this study was to evaluate the clinical and
      radiographic outcomes of revision of the femoral component of a hip arthroplasty
      with use of an impaction bone-grafting technique and a cemented polished stem.
      METHODS: Thirty-three consecutive femoral reconstructions that were performed
      between March 1991 and February 1996 with use of the X-change femoral revision
      system, fresh-frozen morselized allograft, and a cemented polished Exeter stem
      were followed prospectively. Femoral bone stock defects were classified according
      to the Endoklinik classification. The average age of the patients at the time of
      the femoral component revision was sixty-three years. No patient was lost to
      follow-up, which was performed at a minimum of eight years, but eight patients
      had died. None of the deaths was related to the surgery. RESULTS: No femoral
      reconstruction had been rerevised at a mean of 10.4 years postoperatively. There
      was one unrecognized intraoperative fracture, which healed following nonoperative
      treatment. There were three postoperative femoral fractures, all through cortical
      defects at the level of the tip of the prostheses. All fractures healed after
      plate fixation, and all femoral implants were left in situ. The average
      subsidence of the stem within the cement mantle was 3 mm; seven stems migrated 5
      mm. The average Harris hip score improved from 49 points prior to surgery to 85
      points (range, 68 to 100 points) at the time of this review. Subsidence did not
      affect the Harris hip score. Kaplan-Meier analysis, with an end point of femoral
      revision for any reason, showed a survival rate of 100% (one-sided 95% confidence
      interval, 100% to 91.3%). CONCLUSIONS: Femoral revision with use of an impaction
      bone-grafting technique and a cemented polished stem resulted in an excellent
      prosthetic survival rate at eight to thirteen years postoperatively. The major
      problem that occurred was a femoral fracture in four patients.

PMID- 16951099
TI  - Indirect reduction and plate fixation, without grafting, for periprosthetic
      femoral shaft fractures about a stable intramedullary implant. Surgical
      Technique.
AB  - BACKGROUND: The application of indirect reduction techniques has improved
      fracture-healing and reduced the need for bone-grafting compared with the
      outcomes of older, direct reduction techniques. We investigated the results of
      such indirect reduction techniques for the treatment of periprosthetic femoral
      shaft fractures. METHODS: Fifty consecutive patients with a femoral shaft
      fracture about a stable intramedullary implant (a Vancouver Type-B1 fracture)
      were treated with a protocol that included open reduction with use of indirect
      reduction techniques and internal fixation with a single lateral plate without
      structural allografting or other bone-grafting. Four patients died in the early
      postoperative period, and five had inadequate follow-up. The remaining forty-one
      patients (average age, seventy-two years) were evaluated clinically and
      radiographically at an average of twenty-four months. RESULTS: All fractures
      healed in satisfactory alignment at an average of twelve weeks (range, seven to
      twenty-three weeks) after the index procedure. One patient had one fractured
      cable and two others had one fractured screw, but all of the fractures healed
      without evidence of implant loosening or malalignment. There was one deep
      infection in the perioperative period. Thirty of the forty-one patients returned
      to their baseline ambulatory status. CONCLUSIONS: The results of this study
      support the use of indirect open reduction and internal fixation with a single
      extraperiosteal lateral plate, without the use of allograft struts, for the
      treatment of a femoral shaft fracture about a stable intramedullary implant.

PMID- 16951100
TI  - Physeal sparing reconstruction of the anterior cruciate ligament in skeletally
      immature prepubescent children and adolescents. Surgical technique.
AB  - BACKGROUND: The management of anterior cruciate ligament injuries in skeletally
      immature patients is controversial. Conventional adult reconstruction techniques
      risk potential iatrogenic growth disturbance due to physeal damage. The purpose
      of this study was to evaluate the results of a physeal sparing, combined intra
      articular and extra-articular reconstruction technique in prepubescent skeletally
      immature children. METHODS: Between 1980 and 2002, forty-four skeletally immature
      prepubescent children and adolescents who were in Tanner stage 1 or 2 (with a
      mean chronological age of 10.3 years) underwent physeal sparing, combined intra
      articular and extra-articular reconstruction of the anterior cruciate ligament
      with use of an autogenous iliotibial band graft. Twenty-seven patients had
      additional meniscal surgery. Functional outcome, graft survival, radiographic
      outcome, and growth disturbance were evaluated at a mean of 5.3 years after
      surgery. RESULTS: Two patients underwent a revision reconstruction for graft
      failure at 4.7 and 8.3 years postoperatively. In the remaining forty-two
      patients, the mean International Knee Documentation subjective knee score (and
      standard deviation) was 96.7 +/- 6.0 points, and the mean Lysholm knee score was
      95.7 +/- 6.7 points. The results of the Lachman examination for anterior cruciate
      ligament integrity were normal for twenty-three patients, nearly normal for
      eighteen patients, and abnormal for one patient. The results of the pivot-shift
      examination were normal for thirty-one patients and nearly normal for eleven
      patients. Four of the twenty-three patients who underwent concurrent meniscal
      repair had a repeat arthroscopic meniscal repair or partial meniscectomy. The
      mean growth in total height from the time of surgery to the final follow-up
      evaluation was 21.5 cm. No patient had an angular deformity measured
      radiographically or a discrepancy in the length of the lower extremities measured
      clinically. CONCLUSIONS: Physeal sparing, combined intra-articular and extra
      articular reconstruction of the anterior cruciate ligament with use of an
      autogenous iliotibial band graft in skeletally immature prepubescent children and
      adolescents provides excellent functional outcome with a low revision rate and a
      minimal risk of growth disturbance.

PMID- 16951101
TI  - Chondral resurfacing of articular cartilage defects in the knee with the
      microfracture technique. Surgical technique.
AB  - BACKGROUND: Microfracture is a frequently used technique for the repair of
      articular cartilage lesions of the knee. Despite the popularity of the technique,
      prospective information about the clinical results after microfracture is still
      limited. The purpose of our study was to identify the factors that affect the
      clinical outcome from this cartilage repair technique. METHODS: Forty-eight
      symptomatic patients with isolated full-thickness articular cartilage defects of
      the femur in a stable knee were treated with the microfracture technique.
      Prospective evaluation of patient outcome was performed for a minimum follow-up
      of twenty-four months with a combination of validated outcome scores, subjective
      clinical rating, and cartilage-sensitive magnetic resonance imaging. RESULTS: At
      the time of the latest follow-up, knee function was rated good to excellent for
      thirty-two patients (67%), fair for twelve patients (25%), and poor for four
      (8%). Significant increases in the activities of daily living scores,
      International Knee Documentation Committee scores, and the physical component
      score of the Short Form-36 were demonstrated after microfracture (p < 0.05). A
      lower body-mass index correlated with higher scores for the activities of daily
      living and SF-36 physical component, with the worst results for patients with a
      body-mass index of >30 kg/m(2). Significant improvement in the activities of
      daily living score was more frequent with a preoperative duration of symptoms of
      less than twelve months (p < 0.05). Magnetic resonance imaging in twenty-four
      knees demonstrated good repair-tissue fill in the defect in thirteen patients
      (54%), moderate fill in seven (29%), and poor fill in four patients (17%). The
      fill grade correlated with the knee function scores. All knees with good fill
      demonstrated improved knee function, whereas poor fill grade was associated with
      limited improvement and decreasing functional scores after twenty-four months.
      CONCLUSIONS: Microfracture repair of articular cartilage lesions in the knee
      results in significant functional improvement at a minimum follow-up of two
      years. The best short-term results are observed with good fill grade, low body
      mass index, and a short duration of preoperative symptoms. A high body-mass index
      adversely affects short-term outcome, and a poor fill grade is associated with
      limited short-term durability.

PMID- 16951102
TI  - Use of distal femoral osteoarticular allografts in limb salvage surgery. Surgical
      technique.
AB  - BACKGROUND: As diagnostic and therapeutic techniques improve, patients with a
      musculoskeletal sarcoma should expect longer survival, fewer complications and
      side effects, and an improved quality of life. Functional longevity of the
      reconstruction after resection of the tumor becomes a major concern, especially
      in young and physically active patients. The purpose of this study was to analyze
      the mid-term and long-term survival of reconstructions with a distal femoral
      osteoarticular allograft in a series of patients. METHODS: We retrospectively
      reviewed the results of eighty reconstructions with a distal femoral
      osteoarticular allograft following resection of a bone tumor in seventy-six
      patients. The mean duration of follow-up was eighty-two months. The rates of
      survival of the allograft and the joint surface were estimated with use of the
      Kaplan-Meier method. Cox regression analysis was performed to determine whether
      age, gender, the percentage of the femur that had been resected, and the use of
      chemotherapy were independent prognostic factors. Functional and radiographic
      results were documented according to the Musculoskeletal Tumor Society scoring
      system at the time of the latest follow-up. RESULTS: Five patients were lost to
      follow-up, leaving seventy-five allografts in seventy-one patients available for
      study. Thirteen patients (thirteen allografts) died of tumor-related causes
      without allograft failure before a two-year radiographic follow-up could be
      performed. Of the remaining sixty-two allografts, fourteen failed: six failed as
      a result of infection; four, because of local recurrence; one, because of massive
      resorption; and three, as a result of fracture. At the time of final follow-up,
      at a mean of 125 months, forty-eight allografts were still in place. The overall
      rate of allograft survival was 78% at both five and ten years, and the rate of
      allograft survival without the need for resurfacing with a knee prosthesis was
      71% at both five and ten years. With the numbers available, age, gender, the
      percentage of the femur that had been resected, and the use of chemotherapy were
      not found to have a significant effect on the overall allograft survival rates.
      The patients who retained the original allograft had good or excellent functional
      and radiographic results. CONCLUSIONS: The life expectancy for most patients with
      a highly aggressive or malignant tumor in the distal part of the femur is now
      several decades. In this study, we found a high rate of survival of distal
      femoral allograft reconstructions at both five and ten years.

PMID- 16951103
TI  - Percutaneous autologous bone-marrow grafting for nonunions. Surgical technique.
AB  - BACKGROUND: Bone marrow aspirated from the iliac crest contains progenitor cells
      that can be used to obtain bone-healing of nonunions. However, there is little
      available information regarding the number and concentration of these cells that
      are necessary to obtain bone repair. The purpose of this study was to evaluate
      the number and concentration of progenitor cells that were transplanted for the
      treatment of nonunion, the callus volume obtained after the transplantation, and
      the clinical healing rate. METHODS: Marrow was aspirated from both anterior iliac
      crests, concentrated on a cell separator, and then injected into sixty
      noninfected atrophic nonunions of the tibia. Each nonunion received a relatively
      constant volume of 20 cm(3) of concentrated bone marrow. The number of progenitor
      cells that was transplanted was estimated by counting the fibroblast colony
      forming units. The volume of mineralized bone formation was determined by
      comparing preoperative computerized tomography scans with scans performed four
      months following the injection. RESULTS: The aspirates contained an average (and
      standard deviation) of 612 +/- 134 progenitors/cm(3) (range, 12 to 1224
      progenitors/cm(3)) before concentration and an average of 2579 +/- 1121
      progenitors/cm(3) (range, 60 to 6120 progenitors/cm(3)) after concentration. An
      average total of 51 x 10(3) fibroblast colony-forming units was injected into
      each nonunion. Bone union was obtained in fifty-three patients, and the bone
      marrow that had been injected into the nonunions of those patients contained
      >1500 progenitors/cm(3) and an average total of 54,962 +/- 17,431 progenitors.
      The concentration (634 +/- 187 progenitors/cm(3)) and the total number (19,324 +/
      6843) of progenitors injected into the nonunion sites of the seven patients in
      whom bone union was not obtained were both significantly lower (p = 0.001 and p <
      0.01, respectively) than those in the patients who obtained bone union. The
      volume of the mineralized callus measured at four months on the computerized
      tomography scans of the patients who had union ranged from 0.8 to 5.3 cm(3)
      (mean, 3.1 cm(3)). There was a positive correlation between the volume of
      mineralized callus at four months and the number (p = 0.04) and concentration (p
      = 0.01) of fibroblast colony-forming units in the graft. There was a negative
      correlation between the time needed to obtain union and the concentration of
      fibroblast colony-forming units in the graft (p = 0.04). CONCLUSIONS:
      Percutaneous autologous bone-marrow grafting is an effective and safe method for
      the treatment of an atrophic tibial diaphyseal nonunion. However, its efficacy
      appears to be related to the number of progenitors in the graft, and the number
      of progenitors available in bone marrow aspirated from the iliac crest appears to
      be less than optimal in the absence of concentration.

PMID- 16951104
TI  - Primary nonoperative treatment of moderately displaced two-part fractures of the
      radial head.
AB  - BACKGROUND: Moderately displaced two-fragment fractures of the radial head have
      been treated predominantly nonoperatively. Recently, however, open reduction and
      internal fixation has gradually gained interest, without clear evidence that
      initial nonoperative treatment leads to an unfavorable outcome. As a consequence,
      the purpose of the present study was to evaluate the long-term outcome after the
      initial nonoperative treatment of this type of fracture. METHODS: Fifteen men and
      thirty-four women, with a mean age of forty-nine years at the time of the injury,
      were included in the study. All patients initially had been managed
      nonoperatively for a two-fragment fracture of the radial head that was displaced
      2 to 5 mm and that included >/=30% of the joint surface (a Mason type-IIa
      fracture). Early mobilization had been used for twenty-seven patients, and cast
      immobilization for a mean of two weeks (range, one to four weeks) had been used
      for twenty-two. All patients were reevaluated with a questionnaire after a mean
      of nineteen years, and thirty-four also had a clinical and a radiographic
      evaluation. Six patients had had a delayed radial head excision because of an
      unsatisfactory primary outcome. RESULTS: Forty of the forty-nine patients had no
      subjective complaints, eight were slightly impaired as the result of occasional
      elbow pain, and one had daily pain. Flexion was slightly impaired in the injured
      elbows as compared with the uninjured elbows (137 degrees +/- 8 degrees compared
      with 139 degrees +/- 7 degrees ), as was extension (-3 degrees +/- 7 degrees
      compared with 1 degrees +/- 5 degrees ) and supination (86 degrees +/- 7 degrees
      compared with 88 degrees +/- 4 degrees ) (p < 0.05 for all comparisons). The
      prevalence of degenerative changes on radiographs was higher for the injured
      elbows than for the uninjured elbows (82% [twenty-eight of thirty-four] compared
      with 21% [seven of thirty-four]; p < 0.01). CONCLUSIONS: The initial nonoperative
      treatment of Mason type-IIa fractures of the radial head that are displaced by 2
      to 5 mm is associated with a predominantly favorable outcome, especially if a
      delayed radial head excision is performed in the few cases in which the early
      outcome is unsatisfactory. LEVEL OF EVIDENCE: Therapeutic Level IV.

PMID- 16951105
TI  - Rotational acetabular osteotomy for advanced osteoarthritis secondary to
      dysplasia of the hip.
AB  - BACKGROUND: Satisfactory intermediate and long-term results of rotational
      acetabular osteotomy for the treatment of early osteoarthritis secondary to
      developmental dysplasia of the hip have been reported. The purpose of this study
      was to examine the results of rotational acetabular osteotomy in patients with
      advanced osteoarthritis secondary to developmental dysplasia of the hip. METHODS:
      We performed a retrospective review of the results of rotational acetabular
      osteotomy in forty-three patients (forty-three hips). All of the patients had
      radiographic evidence of advanced-stage osteoarthritis, defined as narrowing of
      the joint space with cystic radiolucencies and small osteophytes according to the
      staging system of the Japanese Orthopaedic Association. Forty-one patients were
      female, and two were male. The mean age was 43.8 years at the time of surgery,
      and the mean duration of follow-up was 8.5 years. Clinical follow-up was
      performed with use of the system of Merle d'Aubigne and Postel. The center-edge
      angle, acetabular roof angle, head lateralization index, and minimum width of the
      joint space were measured on radiographs made preoperatively, postoperatively,
      and at the time of final follow-up. Postoperative joint congruency was classified
      into four grades. RESULTS: The mean preoperative Merle d'Aubigne clinical score
      was 13.3 points, which improved to a mean of 15.4 points at the time of the
      latest follow-up (p < 0.0001). The mean center-edge angle improved from 0.7
      degrees preoperatively to 29 degrees at three months postoperatively (p <
      0.0001), the mean acetabular roof angle improved from 30 degrees to 11 degrees (p
      < 0.0001), the mean head lateralization index improved from 0.69 to 0.65 (p <
      0.01), and the mean minimum width of the joint space improved from 2.2 to 2.5 mm
      (p < 0.0003). Ten hips had radiographic evidence of progression of
      osteoarthritis. Kaplan-Meier survivorship analysis, with radiographic signs of
      progression of osteoarthritis as the end point, predicted a ten-year survival
      rate of 72.2%. CONCLUSIONS: Rotational acetabular osteotomy for advanced
      osteoarthritis secondary to dysplasia of the hip in properly selected patients
      can improve clinical scores and is associated with a lack of radiographic signs
      of progression of osteoarthritis in most patients. LEVEL OF EVIDENCE: Therapeutic
      Level IV.

PMID- 16951106
TI  - Early results of the Bernese periacetabular osteotomy: the learning curve at an
      academic medical center.
AB  - BACKGROUND: Most reports on the results of the Bernese periacetabular osteotomy
      for the treatment of developmental dysplasia of the hip have been by the
      originators of the procedure. In 1997, we began to use this osteotomy without
      direct training from the originators of the procedure. METHODS: Seventy-three
      patients (eighty-three hips) underwent a Bernese periacetabular osteotomy between
      1997 and 2003 and were followed prospectively with use of the Harris hip score to
      assess clinical results and with use of anteroposterior pelvic and false-profile
      lateral plain radiographs to assess radiographic results. The three-dimensional
      position of the acetabulum was recorded preoperatively and postoperatively. The
      mean duration of follow-up was forty-six months. RESULTS: The average Harris hip
      score improved from 54 to 87 points (p < 0.001). Three hips (three patients) had
      a conversion to total hip arthroplasty at two, three, and four years after the
      periacetabular osteotomy. Preoperatively, fifty-four of the eighty-three
      acetabula were anteverted, and twenty-nine were either retroverted or had neutral
      wall relationships. Postoperatively, sixty-five hips (78%) were anteverted.
      Radiographically, in preoperatively anteverted hips, the average center-edge
      angle improved from 3 degrees to 29 degrees (p < 0.0001), the average anterior
      center-edge angle improved from 5 degrees to 31 degrees (p < 0.0001), and the
      acetabular index improved from 25 degrees to 5 degrees (p < 0.0001). In
      preoperatively retroverted or neutral hips, the average center-edge angle
      improved from 13 degrees to 33 degrees (p < 0.0001), the average anterior center
      edge angle improved from 15 degrees to 36 degrees (p < 0.0001), and the
      acetabular index improved from 19 degrees to 2 degrees (p < 0.0001).
      Complications included four hematomas, three transient femoral nerve palsies, two
      deep wound infections, and one transient sciatic nerve palsy. Nine of the ten
      major complications and all four of the failed osteotomies occurred in the first
      thirty hips in which the index procedure was performed. CONCLUSIONS: In our
      experience, the early results of the Bernese periacetabular osteotomy have been
      encouraging, with a 92% survival rate at thirty-six months. The occurrence of
      complications demonstrates a substantial learning curve. Recognition of the true
      preoperative acetabular version and reorientation of the acetabulum into an
      appropriately anteverted position have become important factors in surgical
      decision-making. LEVEL OF EVIDENCE: Therapeutic Level IV.

PMID- 16951107
TI  - Depression in orthopaedic trauma patients. Prevalence and severity.
AB  - BACKGROUND: There is a known connection between physical injury and disability
      and emotional distress. Several investigators have shown a relationship between
      trauma, depression, and poor outcomes. The literature on trauma and depression is
      limited with regard to clarifying the relationship between the degree of injury
      and depression and the relationship between physical function of patients with
      less severe injuries and depression. METHODS: One hundred and sixty-one patients
      who presented to our orthopaedic trauma services were enrolled in the study and
      interviewed. We obtained information about patient demographics and administered
      several self-reported outcome measures: the Beck Depression Inventory (BDI), the
      Short Musculoskeletal Function Assessment (SMFA), and the Physical Function-10
      (PF-10) subset of the Short Form-36 (SF-36). We documented the nature and
      severity of the injury or injuries and calculated correlations between the
      outcome measures and the BDI. Injury-specific factors such as the AO Fracture
      Classification, the Abbreviated Injury Scale (AIS), the Injury Severity Score
      (ISS), and the Gustilo and Anderson grade of open fractures were also examined.
      RESULTS: Fifty-five percent of the patients had minimal depression, as measured
      with the BDI; 28% had moderate depression; 13% had moderate-to-severe depression;
      and 3.7% had severe depression. When the somatic elements of the BDI were
      removed, the prevalence of moderate, moderate-to-severe, or severe depression was
      26%. The SMFA scores had a strong negative correlation with the BDI (-0.75; p <
      0.001). Of the injury-specific factors, only open factures were found to have an
      impact on the presence of depression, with an odds ratio of 4.58 (95% confidence
      ratio, 1.57 to 12.35). CONCLUSIONS: The prevalence of clinically relevant
      depression approached 45% in a diverse cohort of orthopaedic trauma patients.
      Global disability is strongly correlated with depression. The presence of an open
      fracture may also increase the risk of depression. LEVEL OF EVIDENCE: Prognostic
      Level II.

PMID- 16951108
TI  - Effect of impact on chondrocyte viability during insertion of human osteochondral
      grafts.
AB  - BACKGROUND: Osteochondral grafts, used to treat chondral and osteochondral
      defects, require high insertional forces that may affect the viability of
      chondrocytes in the graft. The objectives of this study were to (1) measure the
      loading impact during insertion of osteochondral grafts, (2) evaluate the effect
      of insertional loading on chondrocyte viability, and (3) assess this effect on
      chondrocyte apoptosis and activation of caspase-3. METHODS: The distal parts of
      twelve fresh femora from six adult human cadavers were harvested within seventy
      two hours after the death of the donor. From each femur, four 15-mm-diameter
      cylindrical osteochondral grafts were isolated; two of these grafts (a total of
      twenty-four grafts in the study) were transplanted with standard impact insertion
      into recipient sockets in the other condyle of the ipsilateral femur. The other
      two grafts served as unloaded controls. Loads were measured during the insertion
      of ten of the twenty-four transplanted grafts. Full-thickness cartilage disks
      were then removed from the grafts, incubated for up to forty-eight hours, and
      analyzed for cell viability, TUNEL (terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling)-positive reactivity, and caspase-3 activation,
      each as a function of the depth from the articular surface. RESULTS: The
      insertion of an osteochondral graft was characterized, on the average (and
      standard deviation), by 10 +/- 4 impacts, each generating 2.4 +/- 0.9 kN of load
      and 13.3 +/- 4.9 MPa of stress for a duration of 0.57 +/- 0.13 ms with a 0.62 +/-
      0.25 N.s impulse. Impact insertion increased cell death in the superficial 500
      mum to 21% at one hour (p < 0.001) and 47% at forty-eight hours (p < 0.001) and
      also increased cell death in deeper layers at forty-eight hours. Some cell death
      was due to apoptosis, as indicated by an increase in caspase-3 activation at
      eight hours (p < 0.01) and TUNEL-positive cells at forty-eight hours (p < 0.05)
      in the superficial 500 mum of impacted cartilage. CONCLUSIONS: Impact insertion
      of osteochondral grafts generates damaging loads that cause chondrocyte death,
      particularly in the superficial zone, mainly as a result of apoptosis mediated by
      the activation of caspases. CLINICAL RELEVANCE: Chondrocyte death that occurs
      during impact insertion of osteochondral grafts may lead to compromised function.
      Understanding the mechanisms and consequences of such impact loading may provide
      insights into potential therapeutic interventions, or lead to changes in the
      insertion technique, to decrease the cell injury associated with impact loading.

PMID- 16951109
TI  - Prediction of instability in distal radial fractures.
AB  - BACKGROUND: Effective methods of treating an unstable distal radial fracture are
      described in the literature, but there is no reliable method of identifying an
      unstable fracture in time to initiate appropriate treatment. The purposes of this
      study were to identify the predictors of fracture instability and to construct a
      method of prospectively predicting the radiographic outcome. METHODS: Data on
      approximately 4000 distal radial fractures were prospectively recorded over a 5.5
      year period. The database was validated by reexamining a sample of it.
      Demographic data on the patients and mode of injury, as well as the fracture
      classification and measurements, were recorded at the time of presentation.
      Outcome measures consisted of radiographic measurements made at one week and six
      weeks and assessment of carpal alignment at six weeks. Univariate and multiple
      logistic regression analyses were performed to identify the significance of the
      data obtained at presentation in the prediction of early and late instability as
      well as the risk of malunion and carpal malalignment. RESULTS: The predictors of
      early and late instability and malunion differed according to the displacement of
      the fracture at presentation. Patient age, metaphyseal comminution of the
      fracture, and ulnar variance were the most consistent predictors of radiographic
      outcome. Dorsal angulation was not found to be significant in the prediction of
      radiographic outcome for displaced fractures. The degree to which the patient was
      independent was predictive of malunion in minimally displaced and displaced
      fractures. Formulas that are predictive of each of the seven radiographic outcome
      measurements were constructed. CONCLUSIONS: The study succeeded in identifying
      the factors that are prognostic of the radiographic outcome for distal radial
      fractures. Formulas to predict the radiographic outcome were constructed as the
      independent prognostic significance of these factors was quantified. These
      formulas can be used to inform the surgeon's decision about the nature of primary
      treatment of fractures of the distal aspect of the radius. However, they must be
      validated by further studies before they are used to impact the management of
      distal radial fractures. LEVEL OF EVIDENCE: Prognostic Level I.

PMID- 16951110
TI  - Intraoperative fractures of the acetabulum during primary total hip arthroplasty.
AB  - BACKGROUND: The intraoperative occurrence of an acetabular fracture is a rare
      complication of primary total hip arthroplasty. Previous reports have lacked a
      sufficiently large number of subjects to allow for an analysis of the causes and
      appropriate treatment of this problem. METHODS: Between 1990 and 2000, 7121
      primary total hip arthroplasties were performed at our institution. We
      retrospectively reviewed the records in our Total Joint Registry and found that
      twenty-one patients (twenty-one hips) had sustained an intraoperative acetabular
      fracture. Nineteen of these patients (nineteen hips) had been followed until
      revision or for a minimum of two years (mean duration of follow-up, forty-four
      months). We evaluated the anatomic location, cause, treatment, and outcome of the
      fractures. Acetabular component designs were categorized as modular, nonmodular
      (monoblock), true hemispherical, or elliptical, and then each design was analyzed
      for fracture risk. RESULTS: No fractures occurred in association with cemented
      acetabular components. The fracture rate associated with uncemented components
      was 0.4%. In seventeen hips, the acetabular component was judged to be stable
      despite the detection of a fracture and the cup was retained. In four hips, the
      original cup was not stable and therefore was replaced with a design that allowed
      for supplemental screw fixation. All fractures united, and all cups demonstrated
      osseous ingrowth at the time of the most recent follow-up. Elliptical monoblock
      cups were associated with a significantly higher fracture rate than were
      elliptical modular cups (p < 0.0001) and hemispherical modular cups (p < 0.0001).
      There was no significant difference between elliptical modular and hemispherical
      modular components with regard to the fracture rate. CONCLUSIONS: Acetabular
      fracture during primary total hip arthroplasty is a rare complication of
      acetabular fixation without cement. In the present series, retention of a stable
      cup was associated with uneventful osseous ingrowth and excellent early-term
      outcomes. We found a high rate of fracture in association with the use of
      monoblock elliptical components. LEVEL OF EVIDENCE: Therapeutic Level III.

PMID- 16951111
TI  - Serum and breast milk levels of methylmethacrylate following surgeon exposure
      during arthroplasty.
AB  - BACKGROUND: Although pregnant personnel are commonly encouraged to leave the
      operating room during the mixing and application of polymethylmethacrylate, we
      are not aware of any information regarding the safety of exposure to
      methylmethacrylate fumes for breastfeeding women. The present study was performed
      to investigate the concentrations of methylmethacrylate in serum and breast milk
      following exposure during total joint arthroplasty. METHODS: A survey designed to
      determine present-day attitudes to polymethylmethacrylate exposure during
      pregnancy and lactation was sent to members of the Ruth Jackson Orthopaedic
      Society and the National Association of Orthopaedic Nurses. To define the
      presence or absence of a scientific basis for this behavior, serum and breast
      milk samples were collected from two lactating surgeons at selected intervals
      after exposure to methylmethacrylate during eight total joint arthroplasty
      procedures. Two healthy breastfeeding women without exposure to
      methylmethacrylate served as controls. All twenty-five samples were analyzed for
      methylmethacrylate with use of a previously published headspace gas
      chromatography protocol. RESULTS: The gas chromatography protocol detected
      methylmethacrylate at levels as low as 0.5 part per million. No serum or breast
      milk sample demonstrated evidence of methylmethacrylate at that level, nor did
      any surgeon sample test at a higher level than the control specimens. Serum and
      milk samples spiked with methylmethacrylate yielded the analyte peak as expected,
      evidencing no interference from either matrix. CONCLUSIONS: Methylmethacrylate
      was not detectable at the 0.5-part-per-million level in serum or breast milk
      following inhalational exposure during total joint arthroplasty. Although a
      controlled longitudinal relative risk analysis was not performed and the sample
      size was relatively small, pregnant or breastfeeding women may use this
      information to make an informed decision regarding such exposure. LEVEL OF
      EVIDENCE: Therapeutic Level II.

PMID- 16951112
TI  - Hybrid locked plating of osteoporotic fractures of the humerus.
AB  - BACKGROUND: Locked plating techniques recently have gained popularity and offer a
      different biomechanical approach for fracture fixation compared with traditional
      compression plating. In certain clinical situations, it may be preferable to
      employ a "hybrid" construct, in which an unlocked screw is used to assist with
      reduction and locked screws are subsequently used to protect the initial
      reduction. In the present study, we used an unstable osteoporotic fracture model
      of the humerus to determine (1) whether a hybrid construct behaved more like a
      locked construct or a conventional unlocked construct and (2) whether there was a
      difference between locked and unlocked constructs. METHODS: Thirty third
      generation Sawbones humeri were divided into three groups of ten humeri each. A
      locking plate with combination holes was applied to each bone with use of either
      a locked construct, an unlocked construct, or a hybrid construct. To simulate
      purchase in osteoporotic bone, all screw-holes were drilled to 0.3 mm less than
      the diameter of the screw used. Each specimen was then osteotomized in the middle
      part of the shaft, and a 5-mm segment was removed. Oscillating cyclic torsion
      testing was performed to +/-10 N-m for 1000 cycles, torsional stiffness was
      determined at periodic cyclic intervals, and the groups were compared. RESULTS:
      The locked and hybrid constructs demonstrated similar behavior. The initial
      stiffness was similar in these two groups. At ten cycles, the locked and hybrid
      constructs retained 96.3% and 95.4% of their initial stiffness, respectively.
      During the remainder of cycling the stiffness of the locked and hybrid constructs
      decreased in a linear fashion (R(2) = 0.89 and 0.88, respectively), and at 1000
      cycles the stiffness of the locked and hybrid constructs averaged 80.0% and 79.2%
      of the initial values, respectively (p = 1.0). In contrast, the unlocked
      constructs initially were significantly less stiff than both the locked and
      hybrid constructs (p < 0.001). At ten cycles the unlocked constructs retained
      80.4% of their initial stiffness, and at 1000 cycles they retained only 22.3% of
      their initial stiffness. CONCLUSIONS: Hybrid constructs are mechanically similar
      to locked constructs, and both are significantly more stable than unlocked
      constructs under torsional cyclic loading. CLINICAL RELEVANCE: Combining screws
      in the hybrid configuration used in the present study did not compromise the
      mechanical performance of the construct. Hybrid constructs may decrease cost and
      may provide additional clinical value when treating fractures in osteoporotic
      bone.

PMID- 16951113
TI  - The inpatient consultation approach to osteoporosis treatment in patients with a
      fracture. Is automatic consultation needed?
AB  - BACKGROUND: Osteoporosis has been described as a "silent epidemic." We describe
      an osteoporosis consultation program to facilitate the evaluation and treatment
      of inpatients with fragility fractures. METHODS: The inpatient orthopaedic team
      voluntarily requested an osteoporosis consultation on all patients with a
      fragility fracture. The osteoporosis consultant evaluated patients for secondary
      causes and started treatment with calcium, vitamin D, and bisphosphonates unless
      contraindicated. From November 2001 to December 2003, fifty-three osteoporosis
      consultations were performed. A retrospective review of the charts of all
      patients with a hip fracture treated during this twenty-six-month period revealed
      that only 47% were actually seen by the osteoporosis consultants, creating an
      unintentional "nonintervention" cohort of thirty-one patients with a hip
      fracture. Treatment for osteoporosis was assessed by a review of the inpatient
      charts and by a telephone interview after discharge. RESULTS: The study group
      consisted of eighty-four patients, which included fifty-three in the intervention
      cohort (twenty-eight hip and twenty-five other fractures) and thirty-one in the
      nonintervention cohort (all patients with a hip fracture). In the intervention
      cohort, most patients were vitamin-D deficient. Calcium and vitamin-D treatment
      was recommended for all fifty-three patients, and bisphosphonates were
      recommended for forty-one of the fifty-three patients in the intervention cohort.
      In the nonintervention cohort, two patients received calcium and vitamin D and
      one received a bisphosphonate; the difference between the cohorts was significant
      (p < 0.0001). In the intervention cohort, twenty-seven of the thirty-four
      patients who were available for a telephone interview after discharge (at a mean
      of eighteen months) remained on calcium and vitamin D; twenty-two of the thirty
      four patients remained on bisphosphonates. In the nonintervention cohort, only
      one of the twelve patients who were available for follow-up (at a mean of thirty
      nine months) was receiving calcium and vitamin D and none were on bisphosphonate
      treatment. CONCLUSIONS: This consultation program cannot be considered an
      outright success since only half of all patients with a hip fracture actually
      received a consultation. However, osteoporosis consultation, when provided,
      facilitated the recognition of secondary causes and the generic treatment of
      osteoporosis, and inpatients started on treatment generally continued the
      medication after discharge. The results of this study strongly support the need
      for a mechanism of automatic osteoporosis consultation for inpatients with a
      fragility fracture and suggest that, if consultation is reliably obtained, this
      approach can be effective in improving patient care. LEVEL OF EVIDENCE:
      Therapeutic Level III.

PMID- 16951114
TI  - Cost-effectiveness analysis of unicompartmental knee arthroplasty as an
      alternative to total knee arthroplasty for unicompartmental osteoarthritis.
AB  - BACKGROUND: The purpose of this study was to compare the cost-effectiveness of
      unicompartmental knee arthroplasty as an alternative to total knee arthroplasty
      in patients with degenerative arthritis limited to either the medial or lateral
      compartment. METHODS: A decision model was created for the treatment of end-stage
      unicompartmental knee arthritis. A literature review was used to identify
      possible outcomes and their probabilities following treatment with either
      unicompartmental or total knee arthroplasty. Each outcome was weighted for
      quality of life with use of a utility factor, and effectiveness was expressed in
      units of quality-adjusted life years. Gross costs were estimated from Medicare
      reimbursement data for the relevant Current Procedural Terminology and Diagnosis
      Related Group codes. RESULTS: Sensitivity analysis demonstrated that the cost
      effectiveness of unicompartmental knee arthroplasty is dependent on the
      assumption that its durability and functional outcomes approach those of total
      knee arthroplasty. Specifically, it is necessary for the survival of
      unicompartmental implants to be within three to four years of the assumed
      survival of total knee implants for unicompartmental arthroplasty to remain a
      cost-effective alternative. Under these assumptions, the use of unicompartmental
      arthroplasty is a cost-effective choice as it results in incremental gains in
      effectiveness at a cost of less than US dollars 50,000 (in 1998 United States
      dollars) per quality-adjusted life year gained. CONCLUSIONS: This study supports
      unicompartmental knee arthroplasty as a cost-effective alternative for the
      treatment of unicompartmental arthritis when the durability and function of a
      unicompartmental replacement are assumed to be similar to those of a primary
      total knee replacement. This suggests that, with appropriate patient selection,
      the currently available literature supports unicompartmental arthroplasty as a
      cost-effective alternative to total knee arthroplasty. LEVEL OF EVIDENCE:
      Economic and decision analysis, Level II.

PMID- 16951115
TI  - Self-reported upper extremity health status correlates with depression.
AB  - BACKGROUND: The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire
      is the most widely used upper extremity-specific health-status measure. The DASH
      score often demonstrates greater variability than would be expected on the basis
      of objective pathology. This variability may be related to psychosocial factors.
      The purpose of the present study was to investigate the correlation between the
      DASH score and psychological factors for specific diagnoses with relatively
      limited variation in objective pathology. METHODS: Two hundred and thirty-five
      patients with a single, common, discrete hand problem known to have limited
      variations in objective pathology completed the DASH questionnaire, the Eysenck
      Personality Questionnaire-Revised (EPQ-R) to assess neuroticism, the Center for
      Epidemiologic Studies-Depression (CES-D) scale to quantify depressive symptoms,
      and the Pain Anxiety Symptoms Scale (PASS). Forty-five patients had carpal tunnel
      syndrome, forty-four had de Quervain tenosynovitis, forty-eight had lateral elbow
      pain, and seventy-one had a single trigger finger. In addition, twenty-seven
      patients were evaluated six weeks after a nonoperatively treated fracture of the
      distal part of the radius. Relationships between psychosocial factors and the
      DASH score were determined. RESULTS: A significant positive correlation between
      the DASH score and depression was noted for all diagnoses (r = 0.38 to 0.52; p <
      0.01 for all). The DASH score also correlated with pain anxiety for four of the
      five diagnoses (carpal tunnel syndrome, r = 0.40; de Quervain tendinitis, r =
      0.46; lateral elbow pain, r = 0.42; and trigger finger, r = 0.24) (p < 0.05 for
      all). The DASH score was not correlated with neuroticism for any diagnosis. There
      was a highly significant effect of depression (as measured with the CES-D score)
      on the DASH score for all diagnoses. Both the CES-D score (F = 62.68, p < 0.0001)
      and gender (F = 11.36, p < 0.001) were independent predictors of the DASH score.
      CONCLUSIONS: Self-reported upper extremity-specific health status as measured
      with the DASH score correlates with depression and pain anxiety but not
      neuroticism. These data support the contention that psychosocial factors have a
      strong influence on health-status measures.

PMID- 16951116
TI  - Displaced femoral neck fatigue fractures in military recruits.
AB  - BACKGROUND: Displaced fatigue fractures of the femoral neck are uncommon, but
      they can lead to substantial patient morbidity. This study was performed to
      examine the incidence, long-term consequences, radiographic findings, risk
      factors, and complications associated with this fracture. METHODS: Between 1975
      and 1994, twenty-one military recruits sustained a displaced fatigue fracture of
      the femoral neck. Nineteen patients were followed for an average of eighteen
      years. Data regarding the population at risk, hospital records, initial and
      follow-up radiographs, and physical findings were analyzed. The impact of
      instructions from the Finnish Defense Forces, Department of Medical Services,
      provided in 1986 for prevention of femoral neck fatigue fractures was assessed.
      RESULTS: At our institution, the incidence of displaced fatigue fractures of the
      femoral neck was 5.3/100,000 service years from 1975 to 1986, prior to the
      introduction of the prevention regimen in 1986, and it was 2.3/100,000 service
      years (95% confidence interval, 0.11 to 1.31) from 1987 to 1994. The rate of
      Garden type-IV fractures decreased from 3.8 to 0/100,000 service years (95%
      confidence interval, 0 to 0.66) between the first and second time-periods. The
      detection of nondisplaced symptomatic fatigue fractures of the femoral neck
      increased from 15.5 to 53.2/100,000 service years (95% confidence interval, 2.27
      to 5.21) between the two time-periods. Eighteen of the nineteen patients had had
      prodromal symptoms prior to the fracture displacement. Following fracture
      treatment, six patients had delayed union or nonunion of the fracture.
      Osteonecrosis of the femoral head developed in six patients and was significantly
      associated (p = 0.001) with shortening of the femoral neck. Severe osteoarthritis
      developed in eight patients. CONCLUSIONS: A displaced fatigue fracture of the
      femoral neck leads to long-term morbidity in a high percentage of patients. Most
      patients have prodromal symptoms, which provide an opportunity to prevent
      fracture displacement. Our results indicate that, in a military setting, an
      educational program can diminish the incidence of fatigue fracture displacement
      by increasing the awareness of these fractures and their prodromal symptoms and
      by facilitating diagnosis in the early stages before displacement occurs. LEVEL
      OF EVIDENCE: Therapeutic Level III.

PMID- 16951117
TI  - Multicentric giant cell tumor of bone. Clinicopathologic analysis of thirty
      cases.
AB  - BACKGROUND: Giant cell tumor of bone accounts for 4% to 5% of primary bone
      tumors. Approximately 1% of cases present as multiple synchronous or metachronous
      lesions. In this study, we describe the clinicopathologic features of thirty
      cases of multicentric giant cell tumor. METHODS: Thirty patients who had two or
      more separate lesions that had been pathologically confirmed to be giant cell
      tumors were identified. Radiographs were reviewed to evaluate the characteristics
      and locations of the tumors. Histologic reexamination was performed to document
      morphologic features. Clinical information and follow-up data were obtained from
      the medical records. RESULTS: The male:female ratio was 1:2, with an average age
      at presentation of twenty-one years. Fifty-nine percent of the patients were
      younger than twenty years of age. There were ninety-four tumors in the series,
      with an average of three (range, two to nine) per patient. Most tumors had arisen
      in the long bones. Six patients had synchronous ipsilateral involvement of the
      distal part of the femur and the proximal part of the tibia. Radiographically,
      the tumors in long bones manifested as expansive lytic lesions involving the
      metaphysis and extending into the epiphysis. A minority of the tumors were
      confined to the metaphysis, had features of a fibro-osseous or bone-forming
      lesion, or arose in skeletally immature patients. Secondary histopathologic
      changes including fibrohistiocytic regions, reactive bone formation, or
      aneurysmal bone cyst-like changes were not uncommon. Most tumors were treated
      with curettage (64%) or resection (22%). The recurrence rate was similar to that
      of solitary giant cell tumors. Metastatic disease developed in three patients,
      and two patients had malignant transformation. CONCLUSIONS: Multicentric giant
      cell tumors occur more often in younger patients than do solitary giant cell
      tumors, and they frequently present as synchronous lesions around the knee. Some
      tumors appear as bone-forming or fibro-osseous tumors on imaging studies as a
      result of fibrohistiocytic regions and reactive bone formation. The risk of
      recurrence depends on the type of surgery that is performed. LEVEL OF EVIDENCE:
      Therapeutic Level IV.

PMID- 16951118
TI  - Variability in surgical technique for brachioradialis tendon transfer. Evidence
      and implications.
AB  - BACKGROUND: Transfer of the tendon of the brachioradialis muscle to the tendon of
      the flexor pollicis longus restores lateral pinch function after cervical spinal
      cord injury. However, the outcomes of the procedure are unpredictable, and the
      reasons for this are not understood. The purpose of this study was to document
      the degree of variability observed in the performance of this tendon transfer.
      METHODS: The surgical technique used for the brachioradialis tendon transfer was
      assessed in two ways. First, the surgical attachment length of the
      brachioradialis was quantified, after transfer to the flexor pollicis longus,
      with use of intraoperative laser diffraction to measure muscle sarcomere length
      in eleven individuals (twelve limbs) with tetraplegia. Second, ten surgeons who
      regularly performed this procedure were surveyed regarding their tensioning
      preferences. Using a biomechanical model of the upper extremity, we investigated
      theoretically the effect of different surgical approaches on the active muscle
      force-generating capacity of the transferred brachioradialis in functionally
      relevant elbow, wrist, and hand postures. RESULTS: The average sarcomere length
      (and standard deviation) of the transferred brachioradialis was 3.5 +/- 0.3 mum.
      That length was significantly correlated to the in situ sarcomere length (r(2) =
      0.53, p < 0.05). Surgical tensioning preferences varied considerably; however,
      six of the ten surgeons positioned the patient's elbow between full extension (0
      degrees of elbow flexion) and 50 degrees of flexion when selecting the attachment
      length, and six of the ten stated that their goal was to tension the transfer
      slightly tighter than its resting tension. The computer simulations suggested
      that a "tighter" brachioradialis transfer would produce its peak active force in
      an elbow position that is more flexed than the elbow position in which a "looser"
      transfer would produce its peak active force. CONCLUSIONS: This study provides
      evidence that experienced surgeons perform this tendon transfer differently from
      one another. Biomechanical simulations suggested that these differences could
      result in substantial variability in the active force that the transferred
      brachioradialis can produce in functionally relevant postures. CLINICAL
      RELEVANCE: The surgical attachment length and the position of the patient's limb
      at the time of tendon transfer are both controllable and measurable parameters.
      Understanding the relationship between surgical technique and postoperative
      muscle function may provide surgeons with more control of clinical outcomes.

PMID- 16951119
TI  - Revision total elbow arthroplasty for prosthetic fractures.
AB  - BACKGROUND: Fractures of total elbow arthroplasty components are uncommon, and
      the literature provides little guidance regarding the management and outcomes of
      treatment of these complications. The goal of this report was to investigate the
      prevalence and management of fractures of ulnar and humeral components following
      total elbow arthroplasty and to review our experience with cement-within-cement
      reconstruction for revision following such fractures. METHODS: Between 1979 and
      2003, twenty-four patients with a total of twenty-seven fractured total elbow
      arthroplasty components (seventeen ulnar and ten humeral) of different designs
      presented to our institution. Twenty-six implants underwent subsequent revision
      elbow arthroplasty at our institution. Fourteen of those revisions were done with
      a cement-within-cement technique, and twelve, with traditional methods. Twenty
      one patients (twenty-three implants) were available for final follow-up, and data
      that had been acquired prospectively and entered into the institutional
      arthroplasty database were reviewed retrospectively. At the time of final follow
      up, the Mayo Elbow Performance Score (MEPS) was calculated and preoperative,
      postoperative, and most recent radiographs were examined for bone loss, bushing
      wear, and integrity of the bone-cement interface. RESULTS: The prevalences of
      humeral and ulnar component fracture following primary total elbow arthroplasties
      performed at our institution were 0.65% and 1.2%, respectively. At a mean of 5.1
      years following revisions for those fractures, the MEPS was excellent for eight
      patients, good for five, fair for six, and poor for two. The average MEPS was 82
      points following the revision total elbow arthroplasties done with the cement
      within-cement technique and 78 points following the revisions done with the
      traditional method of cement removal and insertion of a revision component.
      Complications included seven intraoperative cortical perforations; five nerve
      injuries, two of which were permanent; three triceps avulsions; and one deep
      infection. CONCLUSIONS: Implant fractures following total elbow arthroplasty are
      uncommon. They occur for several reasons, such as notch sensitivity, component
      design, and high stresses due to bone deficiency. Revision techniques, such as
      cement-within-cement reimplantation, are reliable for relieving pain and
      restoring function; however, the rate and spectrum of complications are a cause
      for concern. LEVEL OF EVIDENCE: Therapeutic Level IV.

PMID- 16951120
TI  - Nicotine delays tendon-to-bone healing in a rat shoulder model.
AB  - BACKGROUND: Many studies have shown that nicotine negatively impacts fracture
      healing and bone fusion processes. However, very little is known about its effect
      on tendon and ligament healing. The goal of the present study was to evaluate the
      effect of nicotine on tendon-to-bone healing. METHODS: Supraspinatus tendons in
      both shoulders of seventy-two rats were transected and repaired to the humeral
      head. Osmotic pumps were implanted subcutaneously, and nicotine or saline
      solution was delivered for ten, twenty-eight, or fifty-six days. Cell morphology
      was evaluated with use of histologic sections. Cells were counted, and
      proliferating cell nuclear antigen (PCNA) immunohistochemistry was performed to
      assess cellular proliferation. In situ hybridization was performed to measure
      type-I collagen mRNA expression. Biomechanical and geometric properties were
      assessed. RESULTS: Inflammation persisted longer in the nicotine group than in
      the saline solution group. Cellular proliferation was higher in the saline
      solution group than in the nicotine group at the early time-points. Type-I
      collagen expression was higher in the saline solution group at twenty-eight days.
      Mechanical properties increased over time in both groups. Maximum stress was
      significantly lower in the nicotine group than in the saline solution group at
      ten days. Maximum force was significantly lower in the nicotine group than in the
      saline solution group at twenty-eight days. Maximum force was significantly
      higher in the nicotine group than in the saline solution group at fifty-six days.
      Stiffness was not different between the groups at any time-point. CONCLUSIONS:
      Nicotine caused a delay in tendon-to-bone healing in a rat rotator cuff animal
      model. Mechanical properties increased over time in both groups, but the
      properties in the nicotine group lagged behind those in the saline solution
      group. Chronic inflammation and decreased cell proliferation may partly explain
      the inferior biomechanical properties in the nicotine group as compared with the
      saline solution group. CLINICAL RELEVANCE: Failure of rotator cuff repair is a
      major clinical problem. The adverse effect of nicotine on rotator cuff healing
      noted in this clinically appropriate animal model may be an important clinical
      consideration.

PMID- 16951121
TI  - Temporary internal distraction as an aid to correction of severe scoliosis.
AB  - BACKGROUND: Halo traction is a well-recognized adjunct for correcting severe
      complex rigid scoliotic curves, but it is associated with complications and is
      contraindicated in the presence of fixed cervical instability, kyphosis, or
      stenosis. In addition, halo traction often requires prolonged hospital stays and
      is not welcomed by all families. These limitations led to consideration of
      temporary internal distraction as an alternative. METHODS: We retrospectively
      reviewed the records of children in whom severe scoliosis had been treated with
      temporary internal distraction. Our goals were to (1) assess whether the use of
      temporary internal distraction can aid in the correction of severe scoliosis and
      (2) identify complications associated with temporary internal distraction and
      compare them with those associated with halo traction. The mean preoperative
      curve was 104 degrees . All patients underwent initial posterior release of the
      rigid portion of the spine (with six also having anterior release) and placement
      of spinal instrumentation under distraction during spinal cord monitoring. Of the
      ten patients, four had one distraction procedure (i.e., the initial surgery [or
      first distraction] followed by definitive fusion and the remaining six had two
      distraction procedures (i.e., the initial surgery [or first distraction] followed
      by the second distraction) followed by definitive fusion. After distraction, all
      patients underwent posterior spinal fusion with definitive dual-rod fixation. The
      amount of correction was determined by measuring the curve on plain radiographs
      made preoperatively, after each internal distraction procedure, after definitive
      fusion, and at the time of final follow-up. RESULTS: Curve correction after use
      of internal distraction, and before definitive fusion, averaged 53% (from 104
      degrees to 49 degrees ) (range, 39% [from 70 degrees to 43 degrees ] to 79% [from
      70 degrees to 15 degrees ]). This method facilitated safe, gradual deformity
      correction in all ten patients. The mean time between the initial procedure and
      the definitive fusion was 2.4 weeks. The mean final curve correction was 80%
      (from 104 degrees to 20 degrees ) (range, 73% [from 131 degrees to 35 degrees ]
      to 91% [from 110 degrees to 10 degrees ]). No neurologic deficits or infections
      resulted. CONCLUSIONS: Temporary internal distraction is a viable alternative
      approach to maximizing curve correction in patients undergoing spinal fusion for
      severe scoliosis. LEVEL OF EVIDENCE: Therapeutic Level IV.

PMID- 16951122
TI  - Role of peripatellar retinaculum in transmission of forces within the extensor
      mechanism.
AB  - BACKGROUND: The role of the peripatellar retinaculum as a frontal plane
      stabilizer of the patellofemoral joint has been well established. However, as a
      result of its unique orientation, the retinaculum also may influence the
      distribution of forces within the extensor mechanism. The objective of this study
      was to determine the extent to which the peripatellar retinaculum affects the
      magnitude of forces experienced by the patellar tendon. METHODS: Ten cadaver
      knees were used in this investigation. Each was mounted on a custom test
      apparatus that was fixed to an Instron frame. The extensor mechanism was loaded
      by applying forces through the individual heads of the quadriceps femoris.
      Patellar tendon tension was measured at 0 degrees , 20 degrees , 40 degrees , and
      60 degrees of knee flexion with use of a buckle transducer under two conditions:
      (1) with the peripatellar retinaculum intact, and (2) with the peripatellar
      retinaculum removed. Patellar tendon tension was compared between the two
      conditions across the knee flexion angles. RESULTS: At each knee flexion angle,
      the patellar tendon tension was greater with the retinaculum removed than it was
      with the retinaculum intact. However, the difference was significant only at 0
      degrees and 60 degrees , at which positions the force transmitted to the patellar
      tendon was increased by 16.6% and 9.6%, respectively. CONCLUSIONS: The observed
      increases in patellar tendon tension after removal of the peripatellar
      retinaculum is an indication of the load-sharing function of that structure as a
      part of the extensor mechanism. CLINICAL RELEVANCE: Our results suggest that
      compromise of the peripatellar retinaculum may alter patellar tendon and/or
      patellofemoral joint forces.

PMID- 16951123
TI  - Physician incentives for academic productivity. An analysis of orthopaedic
      department compensation strategies.
AB  - BACKGROUND: Changes in the health-care industry have led to increasing demand for
      physician-driven clinical volume. This environment has altered the traditional
      balance among teaching, research, and service responsibilities for faculty in
      residency training programs. As economic pressures mount and budgets shrink,
      academic departments are exploring ways of paying faculty that would help to
      maintain the global mission of the organization. The purpose of this study was to
      examine the compensation strategy for faculty in academic orthopaedic surgery
      departments in the United States with a focus on compensation methods for
      academic productivity. METHODS: Thirty-one academic orthopaedic surgery residency
      training programs were recruited for the study. Two methods of data collection
      were used: (1) a survey was mailed electronically to the program chairpersons or
      the finance directors, and (2) eight program leaders were interviewed to obtain
      more in-depth information regarding compensation for academic productivity in
      their organizations. RESULTS: All thirty-one programs responded to the survey. To
      compensate faculty for clinical productivity, twenty-two programs used a salary
      and bonus system, two used salary alone, and the remainder used combined methods.
      Nineteen departments had a compensation system that included academic
      productivity, and twelve did not. Of those that compensated for academic work,
      seven used the chair's decision, six used a point system, one used academic rank
      alone, and the remainder used a combination of methods. The point systems varied
      in breadth, focus, and amount of detail. CONCLUSIONS: Most, but not all,
      departments accounted for academic productivity in their compensation system.
      Most programs used the chair's discretion to determine academic bonuses, but
      several departments had developed point systems. There are common themes with
      regard to this issue, including the importance of the academic mission, the need
      for clinical revenues, the value of flexibility and transparency, and the
      importance of culture and leadership.

PMID- 16951124
TI  - Migration of a broken cerclage wire from the patella into the heart. A case
      report.

PMID- 16951125
TI  - Postoperative delirium after hip fracture.

PMID- 16951126
TI  - Symposium. Subspecialty certification: current status of orthopaedic subspecialty
      certification.

PMID- 16951127
TI  - Physician discipline.

PMID- 16951128
TI  - The intention-to-treat principle: a primer for the orthopaedic surgeon.

PMID- 16951129
TI  - What's new in hip arthroplasty.

PMID- 16951130
TI  - Thyroid hormone and Na+-K+-ATPase: more than simple transcription.

PMID- 16951131
TI  - Mice deficient in galectin-1 exhibit attenuated physiological responses to
      chronic hypoxia-induced pulmonary hypertension.
AB  - Pulmonary hypertension (PH) is characterized by sustained vasoconstriction, with
      subsequent extracellular matrix (ECM) production and smooth muscle cell (SMC)
      proliferation. Changes in the ECM can modulate vasoreactivity and SMC
      contraction. Galectin-1 (Gal-1) is a hypoxia-inducible beta-galactoside-binding
      lectin produced by vascular, interstitial, epithelial, and immune cells. Gal-1
      regulates SMC differentiation, proliferation, and apoptosis via interactions with
      the ECM, as well as immune system function, and, therefore, likely plays a role
      in the pathogenesis of PH. We investigated the effects of Gal-1 during hypoxic PH
      by quantifying 1) Gal-1 expression in response to hypoxia in vitro and in vivo
      and 2) the effect of Gal-1 gene deletion on the magnitude of the PH response to
      chronic hypoxia in vivo. By constructing and screening a subtractive library, we
      found that acute hypoxia increases expression of Gal-1 mRNA in isolated pulmonary
      mesenchymal cells. In wild-type (WT) mice, Gal-1 immunoreactivity increased after
      6 wk of hypoxia. Increased expression of Gal-1 protein was confirmed by
      quantitative Western analysis. Gal-1 knockout (Gal-1(-/-)) mice showed a
      decreased PH response, as measured by right ventricular pressure and the ratio of
      right ventricular to left ventricular + septum wet weight compared with their WT
      counterparts. However, the number and degree of muscularized vessels increased
      similarly in WT and Gal-1(-/-) mice. In response to chronic hypoxia, the decrease
      in factor 8-positive microvessel density was similar in both groups.
      Vasoreactivity of WT and Gal-1(-/-) mice was tested in vivo and with use of
      isolated perfused lungs exposed to acute hypoxia. Acute hypoxia caused a
      significant increase in RV pressure in wild-type and Gal-1(-/-) mice; however,
      the response of the Gal-1(-/-) mice was greater. These results suggest that Gal-1
      influences the contractile response to hypoxia and subsequent remodeling during
      hypoxia-induced PH, which influences disease progression.

PMID- 16951132
TI  - Secretory phospholipases A2 stimulate mucus secretion, induce airway
      inflammation, and produce secretory hyperresponsiveness to neutrophil elastase in
      ferret trachea.
AB  - Secretory phospholipases A(2) (sPLA(2)) are increased in the bronchoalveolar
      lavage fluid of patients with asthma and acute respiratory distress syndrome.
      Intratracheal sPLA(2) instillation induces acute lung injury in the rat and
      guinea pig. We hypothesized that sPLA(2) would stimulate mucus secretion in vitro
      and that intratracheal sPLA(2) exposure would induce mucus hypersecretion and
      airway inflammation in the ferret trachea in vivo. In vitro, porcine pancreatic
      sPLA(2) at a concentration of 0.5 or 5 U/ml significantly increased mucous
      glycoconjugate (MG) secretion from the excised ferret trachea. P
      bromophenacylbromide (a sPLA(2) inhibitor), quercetin (a lipoxygenase inhibitor),
      or MK-886 (a 5-lipoxygenase inhibitor), each at 10(-4) M, significantly reduced
      sPLA(2)-induced MG secretion. sPLA(2)-stimulated MG secretion was decreased in
      Ca(2+)-free medium. In vivo, ferrets were intubated for 30 min once per day for 3
      days using an ETT coated with 20 units of porcine pancreatic sPLA(2) mixed in
      water-soluble jelly. Constitutive MG secretion increased 1 day after sPLA(2)
      exposure and returned to control 5 days later. Human neutrophil elastase (HNE) at
      10(-8) M increased MG secretion in the sPLA(2)-exposed trachea compared with that
      in the control trachea, but methacholine at 10(-7) M did not. sPLA(2)-induced
      secretory hyperresponsiveness continued for at least 5 days after sPLA(2)
      exposure ended. sPLA(2) increased tracheal inflammation, MG secretion, and
      secretory hyperresponsiveness to HNE probably through enzymatic action rather
      than by activation of its receptor.

PMID- 16951133
TI  - Calcium signaling in human airway goblet cells following purinergic activation.
AB  - Despite the general importance of Ca(2+) signaling in signal transduction, and of
      goblet cell mucin hypersecretion in inflammatory pulmonary diseases, measurement
      of airway goblet cell intracellular Ca(2+) (Ca(i)(2+)) has not been reported. In
      this article, we describe the results of experiments measuring Ca(i)(2+) in
      primary cultures of human bronchial goblet cells after stimulation with the
      purinergic agonist adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS) and phorbol 12
      myristate 13-acetate (PMA). Ca(2+) signaling in human goblet cells after
      purinergic stimulation follows the classic paradigm of a Ca(i)(2+) transient from
      a basal activity of 110 nM to a peak response of 260.1 +/- 41.2 nM within 2 min,
      followed by a long superbasal plateau (155.3 +/- 0.2 nM) between 10 and 15 min.
      The rise in Ca(i)(2+) appears to result from a mobilization of intracellular
      stores, because the transient was nearly abolished by inhibition of PLC with the
      phosphatidylinositol-specific PLC inhibitor U-73122, and it was not affected
      significantly by removal of extracellular Ca(2+). Loading goblet cells with BAPTA
      inhibited the ATPgammaS-induced Ca(2+) transient by 86.0 +/- 13.1%, relative to
      control. Finally, in contrast to the massive effects of high doses of PMA (300
      nM) on mucin secretion from goblet cells, phorbol ester stimulated a small (27.1
      +/- 7% of the ATPgammaS control peak), brief rise in Ca(i)(2+). This diminutive
      signal likely denotes a local Ca(2+) gradient, which may be associated with the
      mucin granule exocytotic process.

PMID- 16951134
TI  - Developmental acquisition of T3-sensitive Na-K-ATPase stimulation by rat alveolar
      epithelial cells.
AB  - Late in gestation, the developing air space epithelium switches from chloride and
      fluid secretion to sodium and fluid absorption. Absorption requires Na-K-ATPase
      acting in combination with apical sodium entry mechanisms. Hypothyroidism
      inhibits perinatal fluid resorption, and thyroid hormone [triiodothyronine (T3)]
      stimulates adult alveolar epithelial cell (AEC) Na-K-ATPase. This study explored
      the developmental regulation of Na-K-ATPase by T3 in fetal rat distal lung
      epithelial (FDLE) cells. T3 increased Na-K-ATPase activity in primary FDLE cells
      from gestational day 19 [both primary FDLE cells at embryonic day 19 (E19) and
      the cell line FD19 derived from FDLE cells at E19]. However, T3 did not increase
      the Na-K-ATPase activity in less mature FDLE cells, including primary E17 and E18
      FDLE cells and the cell line FD18 (derived from FDLE cells at E18). Subsequent
      experiments assessed the T3 signal pathway to define whether it was similar in
      the late FDLE and adult AEC and to determine the site of the switch in
      responsiveness to T3. As in adult AEC, in the FD19 cell line, the
      phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin blocked the T3-induced
      increase in Na-K-ATPase activity and plasma membrane quantity. T3 caused a
      parallel increase in phosphorylation of Akt at Ser473 in FDLE cells from E19, but
      not from E17 or E18. In the FD18 cell line, transient expression of a
      constitutively active mutant of the PI3K catalytic p110 subunit significantly
      augmented the Na-K-ATPase activity and the cell surface expression of Na-K-ATPase
      alpha(1) protein. In conclusion, FDLE cells from E17 and E18 lacked T3-sensitive
      Na-K-ATPase activity but acquired this response at E19. The developmental
      stimulation of Na-K-ATPase by T3 in rat FDLE cells requires activation of PI3K,
      and the acquisition of T3 responsiveness may be at PI3K or upstream in the
      signaling pathway.

PMID- 16951135
TI  - SyMAP: A system for discovering and viewing syntenic regions of FPC maps.
AB  - Previous approaches to comparing gene and chromosome organization between two
      genomes have been based on genetic maps or genomic sequences. We have developed a
      system to align an FPC-based physical map to a genomic sequence based on BAC end
      sequences and sequence-tagged hybridization markers and to align two FPC maps to
      one another based on shared markers and fingerprints. The system, called SyMAP
      (Synteny Mapping and Analysis Program), consists of an algorithm to compute
      synteny blocks and Web-based graphics to visualize the results. The approach to
      calculating the anchors (corresponding elements on the respective maps) maximizes
      the inclusion of anchors with different rates of divergence. Chains (putative
      syntenic sets of anchors) are computed using a dynamic programming algorithm,
      which includes off-diagonal anchors that result from map coordinate errors and
      small inversions. As the gap parameters (the distances allowed between anchors in
      a chain) can vary over different data sets and be difficult to set manually, they
      are automatically computed per data set. The criterion for a chain to be
      acceptable is based on the number of anchors and the Pearson correlation
      coefficient. Neighboring chains are merged into synteny blocks for display. This
      algorithm has been tested with three data sets that vary in the number of BACs,
      BAC end sequences, hybridization markers, distance between anchors, and number
      and antiquity of genome duplication events. The Web-based graphics uses Java for
      a highly interactive display that allows the user to interrogate the evidence of
      synteny.

PMID- 16951136
TI  - Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma
      invasion and metastasis.
AB  - For most carcinomas, progression toward malignancy is accompanied by loss of
      epithelial differentiation and a shift towards a mesenchymal phenotype. This
      process, referred to as epithelial to mesenchymal transition (EMT), exacerbates
      motility and invasiveness of many cell types and is often considered a
      prerequisite for tumor infiltration and metastasis. However, there are numerous
      examples of advanced carcinomas that adopt some mesenchymal features, yet retain
      characteristics of well-differentiated epithelial cells. We provide a review of
      these reports and describe mechanisms to explain the morphologic and molecular
      heterogeneity and plasticity of malignant carcinoma cells, including incomplete
      EMT, reversion to an epithelial phenotype, and collective migration. We suggest
      that these mechanisms can manifest in a series of independent and reversible
      steps and that EMT represents just one mechanism in the global metastatic
      carcinoma development process.

PMID- 16951137
TI  - Breast cancer in African-American women: differences in tumor biology from
      European-American women.
AB  - Disparities exist between African-American and European-American women in the
      incidence and nature of breast cancer. African-American women are more often
      diagnosed with breast cancer at an earlier age and with more aggressive disease,
      characterized by higher grade and negative estrogen and progesterone receptor
      status. Recent findings reveal specific gene expression patterns associated with
      the more aggressive breast cancers observed in African-American women. An
      overview of the current literature about racial differences in breast cancer
      prompts questions for future research to elucidate causes for the apparent
      disparities in tumor biology.

PMID- 16951138
TI  - ARID3B induces malignant transformation of mouse embryonic fibroblasts and is
      strongly associated with malignant neuroblastoma.
AB  - ARID3B, a member of the AT-rich interaction domain (ARID) family of proteins,
      plays an essential role in the survival of neural crest during embryogenesis.
      Here, we report evidence that ARID3B is involved in the development of malignant
      neuroblastoma, a childhood tumor derived from neural crest. (a) ARID3B is
      expressed by all five cell lines derived from neuroblastoma tested by us. (b)
      Analysis of published DNA microarray data of fresh neuroblastoma tumors showed
      that ARID3B is expressed in 80% of stage IV tumors, whereas only in 9% of stage I
      III+IVs tumors. (c) In vitro growth of several neuroblastoma cell lines is
      suppressed significantly by antisense as well as siRNA treatment. (d) An increase
      of the ARID3B expression level by transfection in the SY5Y neuroblastoma cell
      line enhances the malignancy in tumor growth assays in nu/nu mice. (e) ARID3B by
      itself can immortalize mouse embryonic fibroblasts (MEFs) in vitro and confers
      malignancy to MEF when transfected together with MYCN, the best characterized
      oncogene for neuroblastoma. Thus, ARID3B seems to play a key role in the
      malignant transformation of neuroblastoma and may serve not only as a marker of
      malignancy but also as a potential target for cancer therapy of stage IV
      neuroblastoma for which there is currently no effective treatment available.

PMID- 16951139
TI  - TMPRSS2:ERG fusion-associated deletions provide insight into the heterogeneity of
      prostate cancer.
AB  - Prostate cancer is a common and clinically heterogeneous disease with marked
      variability in progression. The recent identification of gene fusions of the 5'
      untranslated region of TMPRSS2 (21q22.3) with the ETS transcription factor family
      members, either ERG (21q22.2), ETV1 (7p21.2), or ETV4 (17q21), suggests a
      mechanism for overexpression of the ETS genes in the majority of prostate
      cancers. In the current study using fluorescence in situ hybridization (FISH), we
      identified the TMPRSS2:ERG rearrangements in 49.2% of 118 primary prostate
      cancers and 41.2% of 18 hormone-naive lymph node metastases. The FISH assay
      detected intronic deletions between ERG and TMPRSS2 resulting in TMPRSS2:ERG
      fusion in 60.3% (35 of 58) of the primary TMPRSS2:ERG prostate cancers and 42.9%
      (3 of 7) of the TMPRSS2:ERG hormone-naive lymph node metastases. A significant
      association was observed between TMPRSS2:ERG rearranged tumors through deletions
      and higher tumor stage and the presence of metastatic disease involving pelvic
      lymph nodes. Using 100K oligonucleotide single nucleotide polymorphism arrays, a
      homogeneous deletion site between ERG and TMPRSS2 on chromosome 21q22.2-3 was
      identified with two distinct subclasses distinguished by the start point of the
      deletion at either 38.765 or 38.911 Mb. This study confirms that TMPRSS2:ERG is
      fused in approximately half of the prostate cancers through deletion of genomic
      DNA between ERG and TMPRSS2. The deletion as cause of TMPRSS2:ERG fusion is
      associated with clinical features for prostate cancer progression compared with
      tumors that lack the TMPRSS2:ERG rearrangement.

PMID- 16951140
TI  - A profile of methyl-CpG binding domain protein occupancy of hypermethylated
      promoter CpG islands of tumor suppressor genes in human cancer.
AB  - Methyl-CpG binding domain (MBD) proteins have been shown to couple DNA
      methylation to transcriptional repression. This biological property suggests a
      role for MBD proteins in the silencing of tumor suppressor genes that are
      hypermethylated at their promoter CpG islands in cancer cells. Despite the
      demonstration of the presence of MBDs in the methylated promoter of several
      genes, we still ignore how general and specific is this association. Here, we
      investigate the profile of MBD occupancy in a large panel of tumor suppressor
      gene promoters and cancer cell lines. Our study shows that most hypermethylated
      promoters are occupied by MBD proteins, whereas unmethylated promoters are
      generally devoid of MBDs, with the exception of MBD1. Treatment of cancer cells
      with the demethylating agent 5-aza-2'-deoxycytidine results in CpG island
      hypomethylation, MBD release, and gene reexpression, reinforcing the notion that
      association of MBDs with methylated promoters is methylation-dependent. Whereas
      several promoters are highly specific in recruiting a particular set of MBDs,
      other promoters seem to be less exclusive. Our results indicate that MBDs have a
      great affinity in vivo for binding hypermethylated promoter CpG islands of tumor
      suppressor genes, with a specific profile of MBD occupancy that it is gene and
      tumor type specific.

PMID- 16951141
TI  - Expression of variant TMPRSS2/ERG fusion messenger RNAs is associated with
      aggressive prostate cancer.
AB  - Recent studies have reported that the majority of prostate cancers express fusion
      genes in which the 5' region of the androgen-regulated TMPRSS2 gene is fused to
      an ETS family transcription factor, most commonly the ERG gene. We have
      characterized in detail the expression of TMPRSS2/ERG fusion mRNAs and correlated
      the isoforms expressed and expression levels with clinical outcome in cancers
      from men undergoing radical prostatectomy. Overall, 59% of clinically localized
      prostate cancers express the TMPRSS2/ERG fusion gene, confirming the initial
      observations of high frequency expression of this fusion mRNA in prostate cancer.
      There was significant variation in the alternatively spliced isoforms expressed
      in different cancers. Expression of an isoform, in which the native ATG in exon 2
      of the TMPRSS2 gene is in frame with exon 4 of the ERG gene, was associated with
      clinical and pathologic variables of aggressive disease. Expression of other
      isoforms, in which the native ERG ATG in exon 3 was the first in-frame ATG, was
      associated with seminal vesicle invasion, which is correlated with poor outcome
      following radical prostatectomy. Cancers not expressing these isoforms tended to
      express higher levels of fusion mRNAs, and in this group, higher expression
      levels of fusion mRNA were present in cancers with early prostate-specific
      antigen recurrence. Thus, both the isoforms of TMPRSS2/ERG fusions expressed and
      expression level may affect prostate cancer progression.

PMID- 16951142
TI  - Tumor cell radiosensitivity is a major determinant of tumor response to
      radiation.
AB  - Substantial evidence suggests that the radiosensitivity of the tumor cells is the
      primary determinant of tumor response to radiation. More recent studies suggest
      that tumor stroma radiosensitivity is the principle determinant of response. To
      assess the relationship between intrinsic tumor cell radiosensitivity and tumor
      response, we altered the intrinsic radiosensitivity of a cloned tumor cell line
      and analyzed the effect of this alteration on tumor response. A cloned tumor cell
      line derived from DNA double-strand break repair--deficient severe combined
      immunodeficient mice was transfected with the double-strand break repair gene DNA
      PKcs. The intrinsic radiosensitivity of the transfected tumor line was decreased
      by a factor of approximately 1.5. The isogenic lines were used to initiate tumors
      in NCr-nu/nu mice. When transplanted in the same strain of mice and exposed to
      the same dose of radiation, the isogenic tumors may be expected to exhibit a
      similar response to radiation if radiation damage to host stroma is the principle
      determinant of response. This was not observed. Over the dose range of 20 Gy in
      four 5-Gy fractions to a single dose of 30 Gy, the 1.5-fold increase in intrinsic
      tumor cell radioresistance conferred by the introduction of DNA-PKcs caused a 1.5
      fold decrease in tumor growth delay. The results show that the intrinsic
      radiosensitivity of tumor cells is a major determinant of tumor response to
      radiation.

PMID- 16951143
TI  - p53 is preferentially recruited to the promoters of growth arrest genes p21 and
      GADD45 during replicative senescence of normal human fibroblasts.
AB  - Replicative senescence is the terminal growth arrest that most normal human cells
      enter into after a fixed number of divisions in vitro, limiting the proliferative
      potential of a cell and preventing genomic instability caused by critically short
      telomeres. Thus, senescence presents a tumor-suppressive mechanism and a barrier
      to tumor formation. However, senescent cells are inherently resistant to
      apoptosis and, as they accumulate in aging tissues, may contribute to organ
      dysfunction and promote tumor progression as part of the stromal environment.
      Replicative life span in normal human cells can be extended by inactivation of
      the tumor suppressor gene p53 or its direct target, the cyclin-dependent kinase
      inhibitor p21, suggesting a direct role for this pathway in senescence. However,
      p53 recruitment to promoters of target genes during replicative senescence has
      not been shown in live cells. In this study, we used chromatin
      immunoprecipitation to determine that p53 preferentially occupied the promoters
      of growth arrest genes p21 and GADD45 in senescent normal human diploid
      fibroblasts but not the promoters of other target genes that recruited p53
      following doxorubicin-induced DNA damage, such as apoptosis regulators TNFRSF10b,
      TNFRSF6, and PUMA. This differential recruitment of p53 in senescent versus
      doxorubicin-treated fibroblasts was accompanied by differences in post
      translational modification of p53. These data provide mechanisms for both the
      growth arrest mediated by p53 and the resistant nature of senescent cells to
      apoptosis despite p53 activity.

PMID- 16951144
TI  - Expression of Delta DNMT3B variants and its association with promoter methylation
      of p16 and RASSF1A in primary non-small cell lung cancer.
AB  - Despite the role of DNMT3B in de novo DNA methylation, a correlation between
      DNMT3B expression and promoter DNA methylation has not being established in
      tumors. We recently reported DeltaDNMT3B, a subfamily of DNMT3B, with seven
      variants, as the predominant expression forms in non-small cell lung cancer
      (NSCLC). We hypothesized that expression of the DeltaDNMT3B variants plays a role
      in promoter methylation formation during lung tumorigenesis. Expression of seven
      DeltaDNMT3B variants was measured in 119 NSCLCs and the corresponding normal
      lungs using reverse transcription-PCR. The expression patterns of DeltaDNMT3B
      variants were analyzed with the status of p16 and RASSF1A promoter methylation in
      the tumors as well as in patients' clinical variables, including outcomes.
      Expression of DeltaDNMT3B variants was detected in 94 of 119 (80%) tumors but in
      only 22 (18%) of the corresponding normal lungs (P < 0.0001). DeltaDNMT3B1,
      DeltaDNMT3B2, and DeltaDNMT3B4 were the most frequently detected transcripts in
      the tumors (62%, 76%, and 46%, respectively). The expression of DeltaDNMT3B
      variants was associated with p16 and RASSF1A promoter methylation in the tumors,
      but the strongest association was between DeltaDNMT3B4 and RASSF1A. Forty-two of
      46 (91%) tumors with RASSF1A promoter methylation expressed DeltaDNMT3B4 compared
      with only 13 of 73 (18%) tumors without the promoter methylation (P < 0.0001).
      Strong associations were also observed between expression of the variants in the
      tumors and in patients' clinical outcomes. Expression of DeltaDNMT3B variants is
      common in NSCLC and may play an important role in the development of promoter
      methylation.

PMID- 16951145
TI  - Interaction of deleted in liver cancer 1 with tensin2 in caveolae and
      implications in tumor suppression.
AB  - Deleted in liver cancer 1 (DLC1) is a recently identified tumor suppressor gene
      frequently underexpressed in hepatocellular carcinoma (HCC). DLC1 encodes a Rho
      GTPase-activating protein domain that exhibits growth-suppressive activity in HCC
      cell lines. Our recent finding has revealed that inhibition of Rho-mediated actin
      stress fiber formation by DLC1 is associated with its growth inhibitory activity.
      In the present study, we identified tensin2 as the novel binding partner of DLC1.
      Tensin2 belongs to a new family of focal adhesion proteins that play key roles in
      cytoskeleton organization and signal transduction. Dysregulation of tensin
      proteins has previously been implicated in human cancers. Tensin2 is highly
      expressed in human liver. Introduction of tensin2 into HCC cell lines with low
      expression of tensin2 caused significant growth inhibition and induction of
      apoptosis. Tensin2 directly interacted with DLC1 in vitro and in vivo. Both
      proteins localized to punctate structures in the cytoplasm. Sequence analysis of
      DLC1 and tensin2 identified caveolin-1 binding motif in both proteins. In vivo
      immunoprecipitation study confirmed that both proteins indeed interacted with
      endogenous caveolin-1, which is the major structural component of caveolae. Our
      findings presented here suggest a new model for the action of DLC1 in
      hepatocytes, whereby DLC1-tensin2 complex interacts with Rho GTPases in caveolae
      to effect cytoskeletal reorganization.

PMID- 16951146
TI  - AKT regulation of estrogen receptor beta transcriptional activity in breast
      cancer.
AB  - Growth factor activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway
      has been shown to activate the estrogen receptor (ER) alpha and to mediate
      tamoxifen resistance in breast cancer. Here, we investigated the regulation of
      the transcriptional activity of the newer ER beta by PI3K-AKT signaling. Tissue
      arrays of breast cancer specimens showed a positive association between the
      expressions of AKT and ER beta in the clinical setting. Reporter gene assays
      using pharmacologic and molecular inhibitors of AKT and constitutively active AKT
      revealed for the first time the ability of AKT to (a) potentiate ER beta activity
      and (b) target predominantly the activation function-2 (AF2) domain of the
      receptor, with a requirement for residue K269. Given the importance of
      coactivators in ER transcriptional activity, we further investigated the possible
      involvement of steroid receptor coactivator 1 (SRC1) and glucocorticoid receptor
      interacting protein 1 (GRIP1) in AKT regulation of ER beta. Mammalian two-hybrid
      assays revealed that AKT enhanced both SRC1 and GRIP1 recruitment to the ER beta
      AF2 domain, and reporter gene analyses revealed that AKT and GRIP1 cooperatively
      potentiated ER beta-mediated transcription to a level much greater than either
      factor alone. Investigations into AKT regulation of GRIP with mammalian one
      hybrid assays showed that AKT potentiated the activation domains of GRIP1 itself,
      and in vitro kinase assays revealed that AKT directly phosphorylated GRIP1. The
      cross-talk between the PI3K-AKT and ER beta pathways, as revealed by the ability
      of AKT to regulate several components of ER beta-mediated transcription, may
      represent an important aspect that may influence breast cancer response to
      endocrine therapy.

PMID- 16951147
TI  - Prognostic significance of nuclear factor-kappaB p105/p50 in human melanoma and
      its role in cell migration.
AB  - Transcriptional factor nuclear factor-kappaB (NF-kappaB) family has been shown to
      play an important role in tumor pathogenesis and serve as a potential target in
      cancer therapy. However, it is necessary to clarify the specific functions of NF
      kappaB members, which would provide the basis for the selective blockade and
      reduction of therapeutic side effects resulting from unspecific inhibition of NF
      kappaB members. In this study, we explored the role of NF-kappaB p105/p50 in
      melanoma pathogenesis in vitro and in vivo. We found that the expression of NF
      kappaB p105/p50 significantly increased in dysplastic nevi, primary melanoma, and
      metastatic melanoma compared with normal nevi (P = 0.0004, chi(2) test).
      Furthermore, NF-kappaB p105/p50 nuclear staining increased with melanoma
      progression and strong NF-kappaB p105/p50 nuclear staining was inversely
      correlated with disease-specific 5-year survival of patients with tumor thickness
      >2.0 mm (P = 0.014, log-rank test). Multivariate Cox regression analysis revealed
      that nuclear expression of NF-kappaB p105/p50 is an independent prognostic factor
      in this subgroup. Moreover, we found that up-regulation of NF-kappaB p50 enhanced
      melanoma cell migration, whereas small interfering RNA knockdown inhibited cell
      migration. In addition, overexpression of NF-kappaB p50 induced RhoA activity and
      Rock-mediated formation of stress fiber in melanoma cells. Taken together, our
      data indicate that NF-kappaB p105/p50 may be an important marker for human
      melanoma progression and prognosis as well as a potentially selective therapeutic
      target.

PMID- 16951148
TI  - Hyperplasia and carcinomas in Pten-deficient mice and reduced PTEN protein in
      human bladder cancer patients.
AB  - PTEN is a tumor suppressor gene mutated in many human cancers. We used the Cre
      loxP system to generate an urothelium-specific null mutation of Pten in mice
      [FabpCrePten(flox/flox) (FPten(flox/flox)) mice]. Histologic examination revealed
      that all FPten(flox/flox) mice exhibited urothelial hyperplasia in which
      component cells showed enlarged nuclei and increased cell size. With time, 10% of
      FPten(flox/flox) mice spontaneously developed pedicellate papillary transitional
      cell carcinomas (TCC). This type of tumor also arose in FPten(flox/flox) mice
      treated with the chemical carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine.
      FPten(flox/flox) urothelial cells were hyperproliferative and showed increased
      activation of the survival signaling molecules Akt and extracellular signal
      regulated kinase. In humans, 53% of primary bladder cancer patients exhibited
      decreased or absent expression of PTEN protein in either the cytoplasm or nucleus
      of tumor cells. In early bladder cancers, PTEN expression was repressed in 42% of
      superficial papillary TCC but in only 8% of cases of carcinoma in situ (CIS). In
      advanced bladder cancers, PTEN protein was significantly reduced (particularly in
      the nucleus) in 94% of cases, and this decrease in PTEN correlated with disease
      stage and grade. Thus, PTEN deficiency may contribute to bladder cancer both by
      initiating superficial papillary TCC and by promoting the progression of CIS to
      advanced invasive and metastatic forms.

PMID- 16951149
TI  - Multiple endocrine neoplasia type 1 interacts with forkhead transcription factor
      CHES1 in DNA damage response.
AB  - Multiple endocrine neoplasia type 1 (MEN1) is a cancer susceptibility syndrome
      affecting several endocrine tissues. Investigations of the biochemical function
      of the MEN1 protein, menin, have suggested a role as a transcriptional
      comodulator. The mechanism by which MEN1 inactivation leads to tumor formation is
      not fully understood. MEN1 was implicated to function in both regulation of cell
      proliferation and maintenance of genomic integrity. Here, we investigate the
      mechanism by which MEN1 affects DNA damage response. We found that Drosophila
      larval tissue and mouse embryonic fibroblasts mutant for the MEN1 homologue were
      deficient for a DNA damage-activated S-phase checkpoint. The forkhead
      transcription factor CHES1 (FOXN3) was identified as an interacting protein by a
      genetic screen, and overexpression of CHES1 restored both cell cycle arrest and
      viability of MEN1 mutant flies after ionizing radiation exposure. We showed a
      biochemical interaction between human menin and CHES1 and showed that the COOH
      terminus of menin, which is frequently mutated in MEN1 patients, is necessary for
      this interaction. Our data indicate that menin is involved in the activation of S
      phase arrest in response to ionizing radiation. CHES1 is a component of a
      transcriptional repressor complex, that includes mSin3a, histone deacetylase
      (HDAC) 1, and HDAC2, and it interacts with menin in an S-phase checkpoint pathway
      related to DNA damage response.

PMID- 16951150
TI  - Expression profiling identifies altered expression of genes that contribute to
      the inhibition of transforming growth factor-beta signaling in ovarian cancer.
AB  - Ovarian cancer is resistant to the antiproliferative effects of transforming
      growth factor-beta (TGF-beta); however, the mechanism of this resistance remains
      unclear. We used oligonucleotide arrays to profile 37 undissected, 68
      microdissected advanced-stage, and 14 microdissected early-stage papillary serous
      cancers to identify signaling pathways involved in ovarian cancer. A total of
      seven genes involved in TGF-beta signaling were identified that had altered
      expression >1.5-fold (P < 0.001) in the ovarian cancer specimens compared with
      normal ovarian surface epithelium. The expression of these genes was coordinately
      altered: genes that inhibit TGF-beta signaling (DACH1, BMP7, and EVI1) were up
      regulated in advanced-stage ovarian cancers and, conversely, genes that enhance
      TGF-beta signaling (PCAF, TFE3, TGFBRII, and SMAD4) were down-regulated compared
      with the normal samples. The microarray data for DACH1 and EVI1 were validated
      using quantitative real-time PCR on 22 microdissected ovarian cancer specimens.
      The EVI1 gene locus was amplified in 43% of the tumors, and there was a
      significant correlation (P = 0.029) between gene copy number and EVI1 gene
      expression. No amplification at the DACH1 locus was found in any of the samples.
      DACH1 and EVI1 inhibited TGF-beta signaling in immortalized normal ovarian
      epithelial cells, and a dominant-negative DACH1, DACH1-Delta DS, partially
      restored signaling in an ovarian cancer cell line resistant to TGF-beta. These
      results suggest that altered expression of these genes is responsible for
      disrupted TGF-beta signaling in ovarian cancer and they may be useful as new and
      novel therapeutic targets for ovarian cancer.

PMID- 16951151
TI  - Silencing of the metastasis suppressor RECK by RAS oncogene is mediated by DNA
      methyltransferase 3b-induced promoter methylation.
AB  - RECK is a membrane-anchored glycoprotein that may negatively regulate matrix
      metalloproteinase activity to suppress tumor invasion and metastasis. Our
      previous study indicated that oncogenic RAS inhibited RECK expression via a
      histone deacetylation mechanism. In this study, we address whether DNA
      methyltransferases (DNMT) participate in the inhibition of RECK by RAS. Induction
      of Ha-RAS(Val12) oncogene increased DNMT3b, but not DNMT1 and DNMT3a, expression
      in 2-12 cells. In addition, induction of DNMT3b by RAS was through the
      extracellular signal-regulated kinase signaling pathway. Oncogenic RAS increased
      the binding of DNMT3b to the promoter of RECK gene and this binding induced
      promoter methylation, which could be reversed by 5'-azacytidine and DNMT3b small
      interfering RNA (siRNA). The MEK inhibitor U0126 also reversed RAS-induced DNMT3b
      binding and RECK promoter methylation. Treatment of 5'-azacytidine and DNMT3b
      siRNA restored RECK expression in 2-12 cells and potently suppressed RAS
      stimulated cell invasion. In addition, the inhibitory effect of 5'-azacytidine on
      RAS-induced cell invasion was attenuated after knockdown of RECK by siRNA.
      Interestingly, human lung cancer cells harboring constitutively activated RAS
      exhibited lower RECK expression and higher promoter methylation of RECK gene. 5'
      Azacytidine and DNMT3b siRNA restored RECK expression in these cells and
      effectively suppressed invasiveness. Collectively, our results suggest that RAS
      oncogene induces RECK gene silencing through DNMT3b-mediated promoter
      methylation, and DNMT inhibitors may be useful for the treatment of RAS-induced
      metastasis.

PMID- 16951152
TI  - Low and high dose UVB regulation of transcription factor NF-E2-related factor 2.
AB  - Transcription factor NF-E2-related factor 2 (Nrf2) regulates antioxidant response
      element (ARE)-mediated expression and coordinated induction of chemoprotective
      proteins in response to chemical stress. In this report, we investigated Nrf2
      response to low and high dose UVB irradiation. Low dose (7.5 J/m(2)) UVB exposure
      of mouse hepatoma, mouse keratinocyte, and human skin fibroblast cells led to the
      nuclear accumulation of Nrf2 and up-regulation of ARE-mediated gene expression.
      On the contrary, and intriguingly, high dose (20 J/m(2)) UVB exposure of cells
      led to the nuclear exclusion of Nrf2 and down-regulation of chemoprotective gene
      expression with possible implications in UVB carcinogenesis. We investigated the
      mechanism by which high dose UVB induced the nuclear exclusion of Nrf2. Prior
      treatment with nuclear export inhibitor, leptomycin B, abrogated the UVB-induced
      nuclear exclusion of Nrf2, indicating that the decrease of Nrf2 in the nucleus
      was due to the nuclear export of Nrf2. High dose UVB increased the
      phosphorylation of Nrf2Y568 which stimulated the nuclear export of Nrf2. Mutation
      of Nrf2Y568 to phenylalanine and src kinase inhibitor PP2 abrogated/reduced the
      UVB-induced phosphorylation of Nrf2Y568 and nuclear exclusion of Nrf2.
      Transfection with src family member Fyn small interfering RNA resulted in the
      nuclear accumulation of Nrf2 and an increase in the expression and UVB induction
      of ARE-mediated gene expression. UVB exposure also induced the nuclear
      localization of Fyn. These results suggest that high dose UVB induced the
      activation/nuclear localization of Fyn which led to increased phosphorylation of
      Nrf2Y568 and enhanced nuclear export of Nrf2. This resulted in nuclear exclusion
      of Nrf2 and down-regulation of ARE-mediated chemoprotective gene expression.

PMID- 16951153
TI  - Smad3 deficiency promotes tumorigenesis in the distal colon of ApcMin/+ mice.
AB  - Colorectal cancer, one of the most common human malignancies in the Western
      world, is often subdivided based on tumor location in either the distal or
      proximal colon. Several mouse models have been developed to study human
      colorectal cancer, but few display this clear distinction between the two colonic
      locations. By crossing Apc(Min/+) and Smad3 mutant mice, we showed that combined
      activation of the Wnt pathway and attenuation of the transforming growth factor
      beta (TGF-beta) pathway causes high multiplicity and rapid onset of invasive
      tumorigenesis almost exclusively in the distal colon, closely mimicking the
      familial adenomatous polyposis (FAP) disease and consisting with distinct
      colorectal cancer etiologies based on tumor location. Transcriptional profiling
      revealed higher expression of several TGF-beta activators in the normal distal
      mucosa than in proximal mucosa, suggesting a stronger reliance on TGF-beta
      mediated growth control in the distal than in the proximal colon.
      Apc(Min/+)Smad3(-/-) mice provide an alternative model to Apc(Min/+) mice to
      study FAP and distal sporadic colorectal cancer. This model will be useful in
      dissecting mechanistic and etiologic differences between proximal and distal
      colonic cancer, whereas the confinement of tumorigenesis to the distal colon
      offers unique advantages in monitoring tumor progression by in vivo imaging.

PMID- 16951154
TI  - Male germ cell-associated kinase, a male-specific kinase regulated by androgen,
      is a coactivator of androgen receptor in prostate cancer cells.
AB  - Androgen receptor (AR) is a ligand-induced transcriptional factor, which plays an
      important role in the normal development of prostate as well as in the
      progression of prostate cancer. Numerous coactivators, which associate with AR
      and function to remodel chromatin and recruit RNA polymerase II to enhance the
      transcriptional potential of AR, have been identified. Among these coactivators,
      few are protein kinases. In this study, we describe the characterization of a
      novel protein kinase, male germ cell-associated kinase (MAK), which serves as a
      coactivator of AR. We present evidence, which indicates that (a) MAK physically
      associates with AR (MAK and AR are found to be coprecipitated from cell extracts,
      colocalized in nucleus, and corecruited to prostate-specific antigen promoter in
      LNCaP as well as in transfected cells); (b) MAK is able to enhance AR
      transactivation potential in an androgen- and kinase-dependent manner in several
      prostate cancer cells and synergize with ACTR/steroid receptor coactivator-3
      coactivator; (c) small hairpin RNA (shRNA) knocks down MAK expression resulting
      in the reduction of AR transactivation ability; (d) MAK-shRNA or kinase-dead
      mutant, when introduced into LNCaP cells, reduces the growth of the cells; and
      (e) microarray analysis of LNCaP cells carrying kinase-dead MAK mutant showed a
      significant impediment of AR signaling, indicating that endogenous MAK plays a
      general role in AR function in prostate cancer cells and likely to be a general
      coactivator of AR in prostate tissues. The highly restricted expression of this
      kinase makes it a potentially useful target for intervention of androgen
      independence.

PMID- 16951155
TI  - Gadd45a suppresses Ras-driven mammary tumorigenesis by activation of c-Jun NH2
      terminal kinase and p38 stress signaling resulting in apoptosis and senescence.
AB  - The Gadd45 family of proteins is known to play a central role as cellular stress
      sensors that modulate the response of mammalian cells to stress inflicted by
      physiologic and environmental stressors. Gadd45a was shown to be a direct target
      to the p53 and BRCA1 tumor suppressor genes, whose loss of function is known to
      play a vital role in breast carcinogenesis; however, the role of Gadd45a in the
      suppression of breast cancer remains unclear. To address this issue, Gadd45a
      deficient mice were crossed with breast cancer prone mouse mammary tumor virus
      Ras mice to generate mice that express activated Ras and differ in their Gadd45a
      status. Using this mouse model, we show that the loss of Gadd45a accelerates Ras
      driven mammary tumor formation, exhibiting increased growth rates and a more
      aggressive histologic phenotype. Moreover, it is shown that accelerated Ras
      driven tumor formation in the absence of Gadd45a results in both a decrease in
      apoptosis, which is linked to a decrease in c-Jun NH(2)-terminal kinase (JNK)
      activation, and a decrease in Ras-induced senescence, which is correlated with a
      decrease in p38 kinase activation. Altogether, these results provide a novel
      model for the tumor-suppressive function of Gadd45a in the context of Ras-driven
      breast carcinogenesis, showing that Gadd45a elicits its function through
      activation of the stress-induced JNK and p38 kinases, which contribute to
      increase in apoptosis and Ras-induced senescence.

PMID- 16951156
TI  - Analysis of genetic alterations and clonal proliferation in children treated for
      acute lymphocytic leukemia.
AB  - The development of risk-directed treatment protocols over the last 25 years has
      resulted in an increase in the survival rates of children treated for cancer. As
      a consequence, there is a growing population of pediatric cancer survivors in
      which the long-term genotoxic effects of chemotherapy is unknown. We previously
      reported that children treated for acute lymphocytic leukemia have significantly
      elevated somatic mutant frequencies at the hypoxanthine-guanine
      phosphoribosyltransferase (HPRT) gene in their peripheral T cells. To understand
      the molecular etiology of the increase in mutant frequencies following
      chemotherapy, we investigated the HPRT mutation spectra and the extent of clonal
      proliferation in 562 HPRT T cell mutant isolates of 87 blood samples from 47
      subjects at diagnosis, during chemotherapy, and postchemotherapy. We observed a
      significant increase in the proportion of CpG transitions following treatment
      (13.6-23.3%) compared with healthy controls (4.0%) and a significant decrease in
      V(D)J-mediated deletions following treatment (0-6.8%) compared with healthy
      controls (17.0%). There was also a significant change in the class type
      percentage of V(D)J-mediated HPRT deletions following treatment. In addition,
      there was a >5-fold increase in T cell receptor gene usage-defined mean clonal
      proliferation from diagnosis compared with the completion of chemotherapeutic
      intervention. These data indicate that unique genetic alterations and extensive
      clonal proliferation are occurring in children following treatment for acute
      lymphocytic leukemia that may influence long-term risks for multifactorial
      diseases, including secondary cancers.

PMID- 16951157
TI  - Chromosomal instability correlates with genome-wide DNA demethylation in human
      primary colorectal cancers.
AB  - DNA hypomethylation is a common trait of colorectal cancer. Studies in tumor cell
      lines and animal models indicate that genome-wide demethylation may cause genetic
      instability and hence facilitate or accelerate tumor progression. Recent studies
      have shown that DNA hypomethylation precedes genomic damage in human
      gastrointestinal cancer, but the nature of this damage has not been clearly
      established. Here, we show a thorough analysis of DNA methylation and genetic
      alterations in two series of colorectal carcinomas. The extent of DNA
      demethylation but not of hypermethylation (both analyzed by amplification of
      intermethylated sites in near 200 independent sequences arbitrarily selected)
      correlated with the cumulated genomic damage assessed by two different techniques
      (arbitrarily primed PCR and comparative genomic hybridization). DNA
      hypomethylation-related instability was mainly of chromosomal nature and could be
      explained by a genome-wide effect rather than by the concurrence of the most
      prevalent genetic and epigenetic alterations. Moreover, the association of p53
      mutations with genomic instability was secondary to DNA hypomethylation and the
      correlation between DNA hypomethylation and genomic instability was observed in
      tumors with and without mutation in the p53 gene. Our data support a direct link
      between genome-wide demethylation and chromosomal instability in human colorectal
      carcinogenesis and are consistent with the studies in model systems demonstrating
      a role of DNA demethylation in inducing chromosomal instability.

PMID- 16951158
TI  - Genome-wide hypomethylation in human glioblastomas associated with specific copy
      number alteration, methylenetetrahydrofolate reductase allele status, and
      increased proliferation.
AB  - Genome-wide reduction in 5-methylcytosine is an epigenetic hallmark of human
      tumorigenesis. Experimentally induced hypomethylation in mice promotes genomic
      instability and is sufficient to initiate tumorigenesis. Here, we report that
      global hypomethylation is common in primary human glioblastomas [glioblastoma
      multiforme (GBM)] and can affect up to an estimated 10 million CpG dinucleotides
      per haploid tumor genome. Demethylation involves satellite 2 (Sat2)
      pericentromeric DNA at chromosomes 1 and 16, the subtelomeric repeat sequence
      D4Z4 at chromosomes 4q and 10q, and interspersed Alu elements. Severe
      hypomethylation of Sat2 sequences is associated with copy number alterations of
      the adjacent euchromatin, suggesting that hypomethylation may be one factor
      predisposing to specific genetic alterations commonly occurring in GBMs. An
      additional apparent consequence of global hypomethylation is reactivation of the
      cancer-testis antigen MAGEA1 via promoter demethylation, but only in GBMs and GBM
      cell lines exhibiting a 5-methylcytosine content below a threshold of
      approximately 50%. Primary GBMs with significant hypomethylation tended to be
      heterozygous or homozygous for the low-functioning Val allele of the rate
      limiting methyl group metabolism gene methylenetetrahydrofolate reductase
      (MTHFR), or had a deletion encompassing this gene at 1p36. Tumors with severe
      genomic hypomethylation also had an elevated proliferation index and deletion of
      the MTHFR gene. These data suggest a model whereby either excessive cell
      proliferation in the context of inadequate methyl donor production from MTHFR
      deficiency promotes genomic hypomethylation and further genomic instability, or
      that MTHFR deficiency-associated demethylation leads to increased proliferative
      activity in GBM.

PMID- 16951159
TI  - Degradation of Tob1 mediated by SCFSkp2-dependent ubiquitination.
AB  - Tob1, a member of the Tob/BTG family, is involved in the control of G(1)-S
      progression by suppressing cyclin D1 expression and acts as a tumor suppressor
      gene. Tob1 was reported to have a quick turnover through the ubiquitin-proteasome
      pathway, but proteins involved in this process are still unknown. We showed that
      Skp2, a substrate-targeting subunit of the SCF (Skp1/Cul1/F-box protein)
      ubiquitin ligase complex, was involved in ubiquitin-dependent degradation of
      Tob1. Skp2 interacted with Tob1 and facilitated ubiquitination of Tob1 in intact
      cells as well as in vitro. Skp2 mutants without the F-box or leucine rich repeat
      were not able to bind to Tob1 and did not enhance ubiquitination of Tob1. Tob1
      was stabilized in both Skp2(-/-) mouse fibroblasts and Skp2 knockdown HeLa cells.
      Moreover, cyclin D1 expression was suppressed in Skp2 knockdown HeLa cells. These
      data suggest that Tob1 is a novel target for degradation by the SCF-Skp2
      ubiquitin ligase.

PMID- 16951160
TI  - Silencing of p29 affects DNA damage responses with UV irradiation.
AB  - Human p29 is a newly identified nuclear protein whose function is largely
      undetermined. We found that p29 associated with chromatin, interacted with MCM3,
      and localized with proliferating cell nuclear antigen foci in the S phase.
      Silencing of p29 using small interfering RNA duplexes reduced DNA synthesis and
      increased the expression of p107, a member of the RB family, and of cyclin
      dependent kinase inhibitor p21, accompanied with a decreased expression of DNA
      polymerase alpha. Lethal events consisting of premature chromatin condensation
      with a reduced Chk1 phosphorylation were observed in p29-depleted cells in
      response to UV irradiation. Intriguingly, the phosphorylation of ataxia
      telangectasia-mutated kinases at S1981 was suppressed in p29-depleted HeLa cells
      with UV irradiation, but not in hydroxyurea- and ionizing radiation-treated
      cells. Taken together, these results reveal a novel function of p29 in the
      regulation of DNA replication checkpoint responses.

PMID- 16951161
TI  - Ephrin-B3 ligand promotes glioma invasion through activation of Rac1.
AB  - Eph receptor tyrosine kinases are involved in nervous system development. Eph
      ligands, termed ephrins, are transmembrane proteins that bind to Eph receptors,
      the mutual activation of which causes repulsive effects in reciprocally
      contacting cells. Previously, we showed that overexpression of EphB2 in glioma
      cells increases cell invasion. Here, expression profiles of ephrin-B family
      members were determined in four glioma cell lines and in invading glioblastoma
      cells collected by laser capture microdissection. Ephrin-B3 mRNA was up-regulated
      in migrating cells of four of four glioma cell lines (1.3- to 1.7-fold) and in
      invading tumor cells of eight of eight biopsy specimens (1.2- to 10.0-fold).
      Forced expression of ephrin-B3 in low expressor cell lines (U87, T98G) stimulated
      cell migration and invasion in vitro and ex vivo, concomitant with tyrosine
      phosphorylation of ephrin-B3. In high expressor cell lines (U251, SNB19), ephrin
      B3 colocalized with Rac1 to lamellipodia of motile wild-type cells. Cells
      transfected with ephrin-B3 small interfering RNA (siRNA) showed significant
      morphologic change and decreased invasion in vitro and ex vivo. Depletion of
      endogenous ephrin-B3 expression abrogated the increase of migration and invasion
      induced by EphB2/Fc, indicating increased invasion is dependent on ephrin-B3
      activation. Furthermore, using a Rac1-GTP pull-down assay, we showed that ephrin
      B3 is associated with Rac1 activation. Reduction of Rac1 by siRNA negated the
      increased invasion by addition of EphB2/Fc. In human glioma specimens, ephrin-B3
      expression and phosphorylation correlated with increasing tumor grade.
      Immunohistochemistry revealed robust staining for phosphorylated ephrin-B and
      ephrin-B3 in invading glioblastoma cells. These data show that ephrin-B3
      expression and signaling through Rac1 are critically important to glioma
      invasion.

PMID- 16951162
TI  - The role of the vascular endothelial growth factor-Delta-like 4 ligand/Notch4
      ephrin B2 cascade in tumor vessel remodeling and endothelial cell functions.
AB  - Vascular endothelial growth factor (VEGF) and Delta-like 4 ligand (DLL4) are the
      only genes whose haploinsufficiency results in vascular abnormalities. Although
      many common pathways are up-regulated in both vascular development and tumor
      angiogenesis and in vascular remodeling, the role of the Delta/Notch pathway has
      not been clearly defined in tumor angiogenesis. In this study, we assessed the
      expression of DLL4, Notch4, and ephrin B2 in transgenic mice developing
      hepatocarcinoma characterized by a strong remodeling of the tumor sinusoids. We
      also investigated the role of VEGF in the expression and biological functions of
      these molecules on human venous endothelial cells. In transgenic livers, we
      showed that DLL4, active Notch4, and ephrin B2 were gradually up-regulated within
      the hepatocarcinoma progression and expressed on tumor sinusoidal endothelial
      cells. In venous endothelial cells, we showed that VEGF up-regulates DLL4 and
      presenilin, and increased the activation of Notch4, leading to an up-regulation
      of ephrin B2 with a down-regulation of Eph B4. We also showed that the activation
      of Notch4 is required for VEGF-induced up-regulation of ephrin B2 and the
      differentiation of human venous endothelial cells in vitro. Accordingly, the
      disruption of Notch4 signaling by pharmacologic inhibition of presenilin or
      addition of soluble DLL4 inhibited the effect of VEGF on human venous endothelial
      cell migration and differentiation. Our study strongly suggests that a
      coordinated activation of DDL4/Notch4 and ephrin B2 pathways downstream of VEGF
      plays a key role in the abnormal remodeling of tumor vessels.

PMID- 16951163
TI  - Ionizing radiation enhances matrix metalloproteinase-2 secretion and invasion of
      glioma cells through Src/epidermal growth factor receptor-mediated p38/Akt and
      phosphatidylinositol 3-kinase/Akt signaling pathways.
AB  - Glioblastoma is a severe type of primary brain tumor, and its highly invasive
      character is considered to be a major therapeutic obstacle. Several recent
      studies have reported that ionizing radiation (IR) enhances the invasion of tumor
      cells, but the mechanisms for this effect are not well understood. In this study,
      we investigated the possible signaling mechanisms involved in IR-induced invasion
      of glioma cells. IR increased the matrix metalloproteinase (MMP)-2 promoter
      activity, mRNA transcription, and protein secretion along with the invasiveness
      of glioma cells lacking functional PTEN (U87, U251, U373, and C6) but not those
      harboring wild-type (WT)-PTEN (LN18 and LN428). IR activated phosphatidylinositol
      3-kinase (PI3K), Akt, and mammalian target of rapamycin, and blockade of these
      kinases by specific inhibitors (LY294002, Akt inhibitor IV, and rapamycin,
      respectively) and transfection of dominant-negative (DN) mutants (DN-p85 and DN
      Akt) or WT-PTEN suppressed the IR-induced MMP-2 secretion in U251 and U373 cells.
      In addition, inhibitors of epidermal growth factor receptor (EGFR; AG490 and
      AG1478), Src (PP2), and p38 (SB203580), EGFR neutralizing antibody, and
      transfection of DN-Src and DN-p38 significantly blocked IR-induced Akt
      phosphorylation and MMP-2 secretion. IR-induced activation of EGFR was suppressed
      by PP2, whereas LY294002 and SB203580 did not affect the activations of p38 and
      PI3K, respectively. Finally, these kinase inhibitors significantly reduced the IR
      induced invasiveness of these cells on Matrigel. Taken together, our findings
      suggest that IR induces Src-dependent EGFR activation, which triggers the p38/Akt
      and PI3K/Akt signaling pathways, leading to increased MMP-2 expression and
      heightened invasiveness of PTEN mutant glioma cells.

PMID- 16951164
TI  - Inducible resistance of tumor cells to tumor necrosis factor-related apoptosis
      inducing ligand receptor 2-mediated apoptosis by generation of a blockade at the
      death domain function.
AB  - Induction of tumor cell resistance to therapeutics has been a major obstacle in
      cancer therapy. Targeting of the death receptors by a natural ligand, tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL), or agonistic
      monoclonal antibodies against TRAIL receptor 1 (TRAIL-R1) or TRAIL receptor 2
      (TRAIL-R2) has been thought to be a promising cancer therapy. To determine
      whether tumor cells are able to generate a resistance to apoptosis induced by an
      anti-TRAIL-R2 antibody, TRA-8, we examined the apoptotic response of human breast
      and ovarian cancer cell lines after treatment with TRA-8. Our results show that
      tumor cell resistance to TRA-8 can be induced by repeated treatment of tumor
      cells with low, non-apoptosis-inducing doses of TRA-8. Interestingly, the induced
      resistance to apoptosis was not due to a global apoptotic defect in tumor cells
      but rather a selective defect in the TRAIL-R2 signaling pathway. Whereas TRA-8
      treated tumor cells developed a selective resistance to TRAIL-R2-mediated
      apoptosis, the apoptotic responses induced by TRAIL, an anti-TRAIL-R1 antibody
      (2E12), and other apoptotic stimuli were not impaired. The expression levels of
      cell surface TRAIL-R2 were not altered and mutations of TRAIL-R2 were not found
      in the resistant cells. The induced TRA-8 resistance was due to a selective
      blockade at the level of the death domain and could be reversed by a wide array
      of chemotherapeutic agents. Proteomic analysis of death-inducing signaling
      complex formation during TRA-8 treatment shows that the translocation of TRAIL-R2
      associated apoptotic proteins was significantly altered. Our results suggest that
      the prevention of tumor cell resistance to therapeutic agents that target the
      death receptors must be taken into consideration.

PMID- 16951165
TI  - p27Kip1 repression of ErbB2-induced mammary tumor growth in transgenic mice
      involves Skp2 and Wnt/beta-catenin signaling.
AB  - Expression of the cyclin-dependent kinase (Cdk) inhibitor (p27(Kip1)) is
      frequently reduced in human tumors, often correlating with poor prognosis.
      p27(Kip1) functions as a haploinsufficient tumor suppressor; however, the
      mechanism by which one allele of p27(Kip1) regulates oncogenic signaling in vivo
      is not well understood. We therefore investigated the mechanisms by which
      p27(Kip1) inhibits mammary tumor onset. Using the common background strain of
      FVB, p27(Kip1) heterozygosity (p27(+/-)) accelerated ErbB2-induced mammary
      tumorigenesis. We conducted microarray analyses of mammary tumors developing in
      mice with genetic haploinsufficiency for p27(Kip1) expressing a mammary-targeted
      ErbB2 oncogene. Global gene expression profiling and Western blot analysis of
      ErbB2/p27(+/-) tumors showed that the loss of p27(Kip1) induced genes promoting
      lymphangiogenesis, cellular proliferation, and collaborative oncogenic signaling
      (Wnt/beta-catenin/Tcf, Cdc25a, Smad7, and Skp2). Skp2 expression was induced by
      ErbB2 and repressed by p27(Kip1). Degradation of p27(Kip1) involves an SCF-type
      E3 ubiquitin ligase, including Skp2. The Skp2 component of the SCF(SKP2) complex
      that degrades p27(Kip1) was increased in ErbB2 tumors correlating with earlier
      tumor onset. In both murine and human ErbB2-overexpressing breast cancers,
      p27(Kip1) levels correlated inversely with Skp2. p27(Kip1) haploinsufficiency
      activated Wnt/beta-catenin/hedgehog signaling. Reintroduction of p27(Kip1)
      inhibited beta-catenin induction of Tcf-responsive genes (Siamosis, c-Myc, and
      Smad7). p27(Kip1) is haploinsufficient for ErbB2 mammary tumor suppression in
      vivo and functions to repress collaborative oncogenic signals including Skp2 and
      Wnt/beta-catenin signaling.

PMID- 16951166
TI  - Human beta-defensin-1, a potential chromosome 8p tumor suppressor: control of
      transcription and induction of apoptosis in renal cell carcinoma.
AB  - Human beta-defensin-1 (hBD-1) is a candidate tumor suppressor gene located on
      chromosome 8p23. Previously, we showed that cancer-specific loss of hBD-1 was
      found in 90% of renal clear cell carcinomas and in 82% of prostate cancers. To
      investigate the possible mechanisms of decreased gene expression and determine
      the function of hBD-1 protein in urological cancers, we sequenced hBD-1 gene
      coding regions in prostatic and renal cancer samples. We then analyzed the
      frequency distribution of promoter polymorphisms and determined the effect of
      these base changes on transcriptional activity of the hBD-1 promoter. A
      polymorphism at -688 bases upstream of the ATG start codon affects hBD-1 promoter
      activity, leading to a rate of reporter gene transcription that is 40% to 50%
      lower than the wild-type sequence when tested in either DU145 or TSU-Pr1 cell
      lines. In addition, a polymorphism at -44 bases was shown to enhance
      transcription up to 2.3 times more than the wild-type sequence in the same cell
      lines. In addition, three novel hBD-1 promoter mutations were found in renal and
      prostate cancer clinical samples. An iso-5-aza-2'-deoxycytidine treatment was
      effective in transcription up-regulation in DU145, suggesting a possible upstream
      methylation-dependent effect. Synthetic hBD-1 peptide inhibited bladder cancer
      cell TSU-Pr1 proliferation. Overexpression of the hBD-1 gene in renal cancer
      cells SW156 resulted in caspase-3-mediated apoptosis. These data support the
      hypothesis that hBD-1 is a potential tumor suppressor gene for urological
      cancers. Promoter point mutations may be responsible for cancer-specific loss of
      hDB-1 expression.

PMID- 16951167
TI  - A1 adenosine receptors in microglia control glioblastoma-host interaction.
AB  - We report that experimental glioblastoma grow more vigorously in A(1) adenosine
      receptor (A(1)AR)-deficient mice associated with a strong accumulation of
      microglial cells at and around the tumors. A(1)ARs were prominently expressed in
      microglia associated with tumor cells as revealed with immunocytochemistry but
      low in microglia in the unaffected brain tissue. The A(1)AR could also be
      detected on microglia from human glioblastoma resections. To study functional
      interactions between tumor and host cells, we studied glioblastoma growth in
      organotypical brain slice cultures. A(1)AR agonists suppressed tumor growth.
      When, however, microglial cells were depleted from the slices, the agonists even
      stimulated tumor growth. Thus, adenosine attenuates glioblastoma growth acting
      via A(1)AR in microglia.

PMID- 16951168
TI  - Redistribution of nucleoside transporters to the cell membrane provides a novel
      approach for imaging thymidylate synthase inhibition by positron emission
      tomography.
AB  - Thymidylate synthase (EC 2.1.1.45) is a key enzyme for the de novo synthesis of
      DNA and as such a target for anticancer drug development. There is a need to
      develop noninvasive methods for assessing thymidylate synthase inhibition in
      tumors. The aim of this study was to assess the potential of 3'-deoxy-3'
      [(18)F]fluorothymidine ([(18)F]FLT) positron emission tomography (PET) for early
      measurement of thymidylate synthase inhibition and to elucidate the cellular
      mechanisms involved. Radiation-induced fibrosarcoma-1 tumor-bearing mice were
      injected with a single i.p. dose of the thymidylate synthase inhibitor 5
      fluorouracil (5-FU; 165 mg/kg) and imaged by [(18)F]FLT-PET at 1 to 2 hours after
      treatment. Deoxyuridine, thymidine kinase 1 (cytoplasmic thymidine kinase;
      EC2.7.1.21), and ATP levels in excised tumors were measured. Cellular assays for
      membrane transport were also done. There was a 1.8-fold increase in the 60-minute
      [(18)F]FLT tumor/heart radioactivity ratio in drug-treated mice compared with
      vehicle controls (P = 0.0016). Plasma and tumor deoxyuridine levels increased
      significantly but thymidine kinase and ATP levels were unchanged. Whole-cell
      assays implicated a (low level) functional role for the type-1 equilibrative
      nucleoside transporter (ENT). There was an increase in type-1 ENT-binding sites
      per cell from 49,110 in untreated cells to 73,142 (P = 0.03) in cells treated
      with 10 microg/mL 5-FU for 2 hours, without a change in transporter affinity (P =
      0.41). We conclude that [(18)F]FLT-PET can be used to measure thymidylate
      synthase inhibition as early as 1 to 2 hours after treatment with 5-FU by a
      mechanism involving redistribution of nucleoside transporters to the plasma
      membrane.

PMID- 16951169
TI  - Differential antiproliferative effects of calcitriol on tumor-derived and
      matrigel-derived endothelial cells.
AB  - The most active metabolite of vitamin D, calcitriol, is growth inhibitory for
      various tumor types in vitro and in vivo and inhibits the growth of endothelial
      cells freshly isolated from tumors [tumor-derived endothelial cells (TDEC)]. We
      compared the effects of calcitriol on Matrigel-derived endothelial cells (MDEC)
      and TDEC isolated from Matrigel plugs and squamous cell carcinoma tumors,
      respectively. TDEC and MDEC expressed vitamin D receptor (VDR) and responded to
      calcitriol by increasing VDR protein expression. Although no mutations were found
      in VDR from either cell type, Scatchard plot analysis revealed a higher ligand
      binding affinity in TDEC (K(d), 0.26 nmol/L) than MDEC (K(d), 0.65 nmol/L). The
      VDR signaling axis in both cells was intact as shown using nuclear translocation
      and 24-hydroxylase promoter-luciferase reporter assays. However, unlike TDEC,
      MDEC were resistant to calcitriol-induced growth inhibition. Calcitriol (10
      nmol/L) resulted in a 12.3% growth inhibition of MDEC compared with 47% in TDEC.
      In TDEC, calcitriol resulted in induction of G(0)/G(1) arrest (10.75%) and
      reduction of S-phase cells (6.8%) with induction of p27 and down-regulation of
      p21 protein expression. Apoptotic effects, determined by Annexin V staining were
      also observed in calcitriol-treated TDEC (38.6%). Calcitriol caused reduced
      expression of p-Erk and p-Akt and an increase of poly(ADP-ribose) polymerase and
      caspase-3 cleavage in TDEC. By contrast, none of these effects on cell cycle or
      apoptosis were seen in calcitriol-treated MDEC. These results show that TDEC were
      more sensitive than MDEC to the antiproliferative effects of calcitriol despite
      apparently normal VDR content and structure of signaling axis in both cell types.

PMID- 16951170
TI  - Functional analysis of alternative isoforms of the transcription factor PAX3 in
      melanocytes in vitro.
AB  - Transcription factor PAX3 has seven isoforms of which PAX3c has been studied
      extensively whereas the functions of the other isoforms are less well known.
      Here, we found that PAX3 isoforms in a stable transfection system have different
      biological functions in mouse melanocytes in vitro. PAX3a and PAX3b had negative
      effects on melanocyte proliferation but had no discernable effect on melanocyte
      growth in soft agar. PAX3a did not affect cell migration and apoptosis but PAX3b
      reduced migration and accelerated apoptosis. PAX3c and PAX3d promoted cell
      proliferation, migration, transformation, and survival. PAX3e reduced melanocyte
      growth; transformation and migration were unchanged and apoptosis was increased
      in vitro. PAX3g did not influence cell proliferation or apoptosis. Cells
      expressing PAX3g were able to grow in soft agar but migration was reduced. PAX3h
      increased cell proliferation, migration, survival, and transformation. These
      functional studies have advanced our understanding of the effects of PAX3
      isoforms in melanocytes and their potential contribution in tumorigenesis.

PMID- 16951172
TI  - DNA damage binding protein component DDB1 participates in nucleotide excision
      repair through DDB2 DNA-binding and cullin 4A ubiquitin ligase activity.
AB  - Functional defect in DNA damage binding (DDB) activity has a direct relationship
      to decreased nucleotide excision repair (NER) and increased susceptibility to
      cancer. DDB forms a complex with cullin 4A (Cul4A), which is now known to
      ubiquitylate DDB2, XPC, and histone H2A. However, the exact role of DDB1 in NER
      is unclear. In this study, we show that DDB1 knockdown in human cells impaired
      their ability to efficiently repair UV-induced cyclobutane pyrimidine dimers
      (CPD) but not 6-4 photoproducts (6-4PP). Extensive nuclear protein fractionation
      and chromatin association analysis revealed that upon irradiation, DDB1 protein
      is translocated from a loosely bound to a tightly bound in vivo chromatin
      fraction and the DDB1 translocation required the participation of functional DDB2
      protein. DDB1 knockdown also affected the translocation of Cul4A component to the
      tightly bound form in UV-damaged chromatin in vivo as well as its recruitment to
      the locally damaged nuclear foci in situ. However, DDB1 knockdown had no effect
      on DNA damage binding capacity of DDB2. The data indicated that DDB2 can bind to
      damaged DNA in vivo as a monomer, whereas Cul4A recruitment to damage sites
      depends on the fully assembled complex. Our data also showed that DDB1 is
      required for the UV-induced DDB2 ubiquitylation and degradation. In summary, the
      results suggest that (a) DDB1 is critical for efficient NER of CPD; (b) DDB1 acts
      in bridging DDB2 and ubiquitin ligase Cul4A; and (c) DDB1 aids in recruiting the
      ubiquitin ligase activity to the damaged sites for successful commencement of
      lesion processing by NER.

PMID- 16951171
TI  - Potential role of Jun activation domain-binding protein 1 as a negative regulator
      of p27kip1 in pancreatic adenocarcinoma.
AB  - Reduced expression of p27 has been associated with poor prognosis in most human
      cancers, including pancreatic adenocarcinoma. Jun activation domain-binding
      protein 1 (JAB1), an activator protein (AP-1) coactivator, previously implicated
      in p27 degradation, is overexpressed in various tumors and correlates with low
      p27 expression. We examined JAB1 and p27 in normal and neoplastic pancreatic
      tissues. Increased JAB1 expression was seen in pancreatic carcinoma samples but
      not in paired normal pancreatic tissues. Immunohistochemical analysis using
      tissue microarrays showed that JAB1 was overexpressed in all 32 (100%) pancreatic
      adenocarcinoma samples tested, predominantly nuclear in 23 (72%) samples and
      predominantly cytoplasmic in 9 (28%) tumors. When 10% was used as a cutoff for
      p27 positivity, p27 was expressed in 11 (34%) of tumors; however, p27 expression
      was localized in the nuclei of tumor cells in only 4 (13%) of the samples.
      Overexpression of the JAB1 in the pancreatic carcinoma cell lines Panc-1, Mia
      PaCa-2, and Panc-28 resulted in decreased p27 expression. Conversely, down
      regulation of JAB1 by short interfering RNA substantially increased p27
      expression and inhibited progression from G(1) to S phase of the cell cycle.
      Interestingly, JAB1-mediated p27 degradation was not impaired when S-phase kinase
      interacting protein 2 (Skp2), an F-box protein required for the ubiquitination
      and consequent degradation of p27, was silenced. Thus, JAB1 may have an Skp2
      independent p27 degradation mechanism in pancreatic cancer cells. These findings
      suggest that JAB1 overexpression is involved in the pathogenesis of pancreatic
      cancer through JAB1-mediated p27 degradation and that control of JAB1 expression
      is a novel therapeutic target in patients with pancreatic adenocarcinomas.

PMID- 16951174
TI  - The generation and regulation of functional diversity of malignant plasma cells.
AB  - Cellular diversity, which is a hallmark of malignancy, can be generated by both
      genetic and nongenetic mechanisms. We describe here variability in the adhesive
      and migratory behavior of malignant plasma cell populations, including multiple
      myeloma-derived lines and primary patient samples. Examination of the plasma cell
      lines ARH-77, CAG, and AKR revealed two distinct subpopulations of cells, one
      displaying highly adhesive properties (type A) and the other consisting of poorly
      adhesive, floating cells (type F). In the ARH-77 cell line, type A cells attach
      better to fibronectin and to human bone fragments and form paxillin-rich focal
      adhesions, whereas type F cells are highly motile and exert integrin-dependent
      bone marrow homing capacity in nonobese diabetic/severe combined immunodeficient
      mice. Flow cytometry indicated that type A cells express significantly higher
      levels of CD45 and CD56 and lower levels of CD138 compared with type F cells.
      Interestingly, culturing of either type A or type F cells under nonselective
      conditions resulted in the development of mixed cell population similar to the
      parental ARH-77 cells. Analysis of bone marrow aspirates of multiple myeloma
      patients revealed that spicules within the aspirates are enriched with type A
      like cells. Nonadherent cells within the aspirate fluids express a marker profile
      similar to type F cells. This study indicates that multiple myeloma patients
      contain heterogeneous populations of malignant plasma cells that display distinct
      properties. Diverse subpopulations of malignant plasma cells may play distinct
      roles in the different biological and clinical manifestations of plasma cell
      dyscrasias, including bone dissemination and selective adhesion to bone marrow
      compartments.

PMID- 16951173
TI  - Low-calcium serum-free defined medium selects for growth of normal prostatic
      epithelial stem cells.
AB  - Stage-specific differentiation markers were used to evaluate the cellular
      composition and the origin of nonimmortalized (PrEC) and immortalized (PZ-HPV7,
      CA-HPV10, RWPE-1, and 957E/hTERT) human prostate cell lines. These studies
      documented that immortalized and nonimmortalized prostate epithelial cells
      established and maintained in low (i.e., <300 micromol/L) Ca(2+) serum-free
      defined (SFD) medium were all derived from normal nonmalignant prostate tissues
      and contain CD133(+)/ABCG2(+)/alpha(2)beta(1)(Hi)/p63(-)/PSCA(-)/AR(-)/PSA(-)
      prostate stem cells. In these cultures, prostate stem cells are able to self
      renew and generate two distinct cell lineages: the minor proliferatively
      quiescent neuroendocrine lineage and the major transit-amplifying cell lineage.
      Subsequently, CD133(-)/ABCG2(-)/alpha(2)beta(1)(Hi)/p63(+)/PSCA(-)/AR(-)/PSA(-)
      transit-amplifying cells proliferate frequently and eventually mature into
      proliferatively quiescent CD133(-)/ABCG2(-)/alpha(2)beta(1)(Lo)/p63(
      )/PSCA(+)/AR(-)/PSA(-) intermediate cells. Such proliferatively quiescent
      intermediate cells, however, do not complete their full maturation into CD133(
      )/ABCG2(-)/alpha(2)beta(1)(Lo)/p63(-)/PSCA(-)/AR(+)/PSA(+) luminal-secretory
      cells in low Ca(2+) SFD medium. Addition of universal type I IFN and synthetic
      androgen (R1881) to culture medium resulted in up-regulation of androgen receptor
      protein expression. However, it failed to induce full differentiation of
      intermediate cells into AR(+)/PSA(+) luminal-secretory cells. Our results
      indicate that such inability of prostate epithelial cells to complete their
      differentiation is due to continuous expression of Notch-1 receptor and its
      downstream effector, Hey-1 protein, which actively suppresses differentiation via
      its ability to transcriptionally repress a series of genes, including the GATA
      family of transcription factors.

PMID- 16951175
TI  - Regulation of transforming growth factor-beta 1-induced apoptosis and epithelial
      to-mesenchymal transition by protein kinase A and signal transducers and
      activators of transcription 3.
AB  - Apoptosis and epithelial-to-mesenchymal transdifferentiation or transition (EMT)
      are crucial for normal development and body homeostasis. The alterations of these
      events are closely related to some pathologic processes, such as tumor formation
      and metastasis, fibrotic diseases of liver and kidney, and abnormal development
      of embryos. The mechanism that underlies the simultaneously occurring apoptosis
      and EMT induced by transforming growth factor-beta (TGF-beta) has not been well
      studied. In this report, we investigated the potential mechanism that underlies
      TGF-beta1-induced apoptosis and EMT. TGF-beta1-induced apoptosis and EMT were
      associated with the activation of protein kinase A (PKA) and signal transducers
      and activators of transcription 3 (STAT3). Inhibition of PKA by specific PKA
      inhibitor H89 or by PKA inhibitor peptide blocked STAT3 activation and suppressed
      TGF-beta1-induced apoptosis and EMT. Furthermore, overexpression of a
      phosphorylation-deficient form of STAT3, but not wild-type STAT3, produced an
      inhibitory effect on TGF-beta1-induced apoptosis and EMT. The results indicate
      that PKA is an upstream regulator for TGF-beta1-induced STAT3 activation and
      plays an important role in TGF-beta1-mediated apoptosis and EMT. These studies
      provided a new insight into the signaling mechanism underlying the apoptosis and
      EMT, which could be of importance in understanding some related physiologic and
      pathologic processes.

PMID- 16951176
TI  - The isopeptidase USP2a protects human prostate cancer from apoptosis.
AB  - Deubiquitinating enzymes can prevent the destruction of protein substrates prior
      to proteasomal degradation. The ubiquitin-specific protease 2a (USP2a)
      deubiquitinates the antiapoptotic proteins Fatty Acid Synthase and Mdm2. Here, we
      show that when USP2a is overexpressed in nontransformed cells, it exhibits
      oncogenic behavior both in vitro and in vivo and prevents apoptosis induced by
      chemotherapeutic agents. Notably, USP2a silencing in several human cancer cell
      lines results in apoptosis. Gene set enrichment analysis, which focuses on groups
      of genes sharing biological function or regulatory pathways, was done on
      microarray expression data from human prostate cancers. The cell death-related
      gene set, as well as a selected cluster of validated p53 target genes, were
      significantly enriched in the low USP2a expression group of tumors. Conversely,
      genes implicated in fatty acid metabolism were significantly associated with
      tumors expressing high USP2a (44%). The expression profile analysis is consistent
      with the effects of USP2a on its known targets, i.e., Fatty Acid Synthase and
      Mdm2, defining a subset of prostate tumors resistant to apoptosis. USP2a thus
      represents a therapeutic target in prostate cancer.

PMID- 16951177
TI  - Antiangiogenic and antitumor effects of SRC inhibition in ovarian carcinoma.
AB  - Src, a nonreceptor tyrosine kinase, is a key mediator for multiple signaling
      pathways that regulate critical cellular functions and is often aberrantly
      activated in a number of solid tumors, including ovarian carcinoma. The purpose
      of this study was to determine the role of activated Src inhibition on tumor
      growth in an orthotopic murine model of ovarian carcinoma. In vitro studies on
      HeyA8 and SKOV3ip1 cell lines revealed that Src inhibition by the Src-selective
      inhibitor, AP23846, occurred within 1 hour and responded in a dose-dependent
      manner. Furthermore, Src inhibition enhanced the cytotoxicity of docetaxel in
      both chemosensitive and chemoresistant ovarian cancer cell lines, HeyA8 and HeyA8
      MDR, respectively. In vivo, Src inhibition by AP23994, an orally bioavailable
      analogue of AP23846, significantly decreased tumor burden in HeyA8 (P = 0.02),
      SKOV3ip1 (P = 0.01), as well as HeyA8-MDR (P < 0.03) relative to the untreated
      controls. However, the greatest effect on tumor reduction was observed in
      combination therapy with docetaxel (P < 0.001, P = 0.002, and P = 0.01, for the
      above models, respectively). Proliferating cell nuclear antigen staining showed
      that Src inhibition alone (P = 0.02) and in combination with docetaxel (P =
      0.007) significantly reduced tumor proliferation. In addition, Src inhibition
      alone and in combination with docetaxel significantly down-regulated tumoral
      production of vascular endothelial growth factor and interleukin 8, whereas
      combination therapy decreased the microvessel density (P = 0.02) and
      significantly affected vascular permeability (P < 0.05). In summary, Src
      inhibition with AP23994 has potent antiangiogenic effects and significantly
      reduces tumor burden in preclinical ovarian cancer models. Thus, Src inhibition
      may be an attractive therapeutic approach for patients with ovarian carcinoma.

PMID- 16951178
TI  - Prohibitin and cofilin are intracellular effectors of transforming growth factor
      beta signaling in human prostate cancer cells.
AB  - A proteomic analysis was pursued to identify new signaling effectors of
      transforming growth factor beta1 (TGF-beta1) that serve as potential
      intracellular effectors of its apoptotic action in human prostate cancer cells.
      The androgen-sensitive and TGF-beta-responsive human prostate cancer cells, LNCaP
      T beta RII, were used as in vitro model. In response to TGF-beta, significant
      posttranslational changes in two proteins temporally preceded apoptotic cell
      death. TGF-beta mediated the nuclear export of prohibitin, a protein involved in
      androgen-regulated prostate growth, to the cytosol in the LNCaP T beta RII cells.
      Cofilin, a protein involved in actin depolymerization, cell motility, and
      apoptosis, was found to undergo mitochondrial translocation in response to TGF
      beta before cytochrome c release. Loss-of-function approaches (small interfering
      RNA) to silence prohibitin expression revealed a modest decrease in the apoptotic
      response to TGF-beta and a significant suppression in TGF-beta-induced cell
      migration. Silencing Smad4 showed that the cellular localization changes
      associated with prohibitin and cofilin action in response to TGF-beta are
      independent of Smad4 intracellular signaling.

PMID- 16951179
TI  - Type I collagen receptor (alpha 2 beta 1) signaling promotes the growth of human
      prostate cancer cells within the bone.
AB  - The most frequent site of prostate cancer metastasis is the bone. Adhesion to
      bone-specific factors may facilitate the selective metastasis of prostate cancer
      to the skeleton. Therefore, we tested whether prostate cancer bone metastasis is
      mediated by binding to type I collagen, the most abundant bone protein. We
      observed that only bone metastatic prostate cancer cells bound collagen I,
      whereas cells that form only visceral metastases failed to bind collagen. To
      confirm the relationship between collagen adhesion and bone metastatic potential,
      a collagen-binding variant of human LNCaP prostate cancer cells was derived
      through serial passage on type I collagen (LNCaP(col)). Fluorescence-activated
      cell sorting analysis showed that LNCaP(col) cells express increased levels of
      the integrin collagen I receptor alpha(2)beta(1) compared with LNCaP cells.
      Antibodies to the alpha(2)beta(1) complex inhibited LNCaP(col) binding to
      collagen, confirming that integrins mediated the attachment. Correspondingly,
      LNCaP(col) cells displayed enhanced chemotactic migration toward collagen I
      compared with LNCaP cells, an activity that could be blocked with alpha(2)beta(1)
      antibodies. To directly test the role of alpha(2)beta(1)-dependent collagen
      binding in bone metastasis, LNCaP and LNCaP(col) cells were injected into the
      tibia of nude mice. After 9 weeks, 7 of 13 (53%) mice injected with LNCaP(col)
      developed bone tumors, whereas 0 of 8 mice injected with LNCaP cells had evidence
      of boney lesions. LNCaP(col) cells were found to express increased levels of the
      metastasis-promoting RhoC GTPase compared with parental LNCaP. We conclude that
      collagen I attachment mediated by alpha(2)beta(1) initiates motility programs
      through RhoC and suggest a mechanism for prostate cancer metastasis to the bone.

PMID- 16951180
TI  - N-myc is an essential downstream effector of Shh signaling during both normal and
      neoplastic cerebellar growth.
AB  - We examined the genetic requirements for the Myc family of oncogenes in normal
      Sonic hedgehog (Shh)-mediated cerebellar granule neuronal precursor (GNP)
      expansion and in Shh pathway-induced medulloblastoma formation. In GNP-enriched
      cultures derived from N-myc(Fl/Fl) and c-myc(Fl/Fl) mice, disruption of N-myc,
      but not c-myc, inhibited the proliferative response to Shh. Conditional deletion
      of c-myc revealed that, although it is necessary for the general regulation of
      brain growth, it is less important for cerebellar development and GNP expansion
      than N-myc. In vivo analysis of compound mutants carrying the conditional N-myc
      null and the activated Smoothened (ND2:SmoA1) alleles showed, that although
      granule cells expressing the ND2:SmoA1 transgene are present in the N-myc null
      cerebellum, no hyperproliferation or tumor formation was detected. Taken
      together, these findings provide in vivo evidence that N-myc acts downstream of
      Shh/Smo signaling during GNP proliferation and that N-myc is required for
      medulloblastoma genesis even in the presence of constitutively active signaling
      from the Shh pathway.

PMID- 16951181
TI  - Calreticulin, a molecular chaperone in the endoplasmic reticulum, modulates
      radiosensitivity of human glioblastoma U251MG cells.
AB  - Radiotherapy is the primary and most important adjuvant therapy for malignant
      gliomas. Although the mechanism of radiation resistance in gliomas has been
      studied for decades, it is still not clear how the resistance is related with
      functions of molecular chaperones in the endoplasmic reticulum. Calreticulin
      (CRT) is a Ca(2+)-binding molecular chaperone in the endoplasmic reticulum.
      Recently, it was reported that changes in intracellular Ca(2+) homeostasis play a
      role in the modulation of apoptosis. In the present study, we found that the
      level of CRT was higher in neuroglioma H4 cells than in glioblastoma cells
      (U251MG and T98G), and was well correlated with the sensitivity to gamma
      irradiation. To examine the role of CRT in the radiosensitivity of malignant
      gliomas, the CRT gene was introduced into U251MG cells, which express low levels
      of CRT, and the effect of overexpression of CRT on the radiosensitivity was
      examined. The cells transfected with the CRT gene exhibited enhanced radiation
      induced apoptosis compared with untransfected control cells. In CRT
      overexpressing cells, cell survival signaling via Akt was markedly suppressed.
      Furthermore, the gene expression of protein phosphatase 2Ac alpha (PP2Ac alpha),
      which is responsible for the dephosphorylation and inactivation of Akt, was up
      regulated in CRT-overexpressing cells, and the regulation was dependent on
      Ca(2+). Thus, overexpression of CRT modulates radiation-induced apoptosis by
      suppressing Akt signaling through the up-regulation of PP2Ac alpha expression via
      altered Ca(2+) homeostasis. These results show the novel mechanism by which CRT
      is involved in the regulation of radiosensitivity and radiation-induced apoptosis
      in malignant glioma cells.

PMID- 16951182
TI  - Chk1- and claspin-dependent but ATR/ATM- and Rad17-independent DNA replication
      checkpoint response in HeLa cells.
AB  - When DNA synthesis is inhibited, DNA replication checkpoint is activated to
      prevent mitosis entry without fully replicated DNA. In Xenopus, caffeine
      sensitive kinases [ataxia telangiectasia mutated (ATM) and ATM-related protein
      (ATR)] are essential in this checkpoint response, but in mammal cells an ATR/ATM
      independent checkpoint response to DNA synthesis inhibition exists. Using HeLa
      cells, which have a caffeine-insensitive checkpoint response, we have analyzed
      here which molecules known to be involved in the DNA replication checkpoint
      participate in the caffeine-insensitive response. When DNA synthesis was
      inhibited in the presence of UCN01 or after knocking down Chk1 expression [Chk1
      small interfering RNA (siRNA)], HeLa cells entered into aberrant mitosis.
      Consequently, Chk1 is essential for both the ATR/ATM-dependent and ATR/ATM
      independent checkpoint response in HeLa cells. Neither wortmannin, Ly294002, nor
      SB202190 abrogated the caffeine-insensitive checkpoint response, indicating that
      DNA-PK and p38 alpha,beta are not involved in the ATR/ATM-independent Chk1
      activation upon DNA synthesis inhibition. Using siRNA to knock down Rad17 and
      claspin, two molecules involved in sensing stalled replication forks, we also
      showed that claspin but not Rad17 is essential for the ATR/ATM-independent
      checkpoint response. Inhibition of DNA synthesis in HeLa cells led to a decrease
      in cyclin B1 protein accumulation that was abrogated when UCN01 was added or when
      claspin was knocked down. We conclude that upon DNA synthesis inhibition, Chk1
      can be activated in a claspin-dependent manner independently of ATR and ATM,
      leading to cyclin B1 down-regulation and providing the cells of an additional
      mechanism to inhibit mitosis entry.

PMID- 16951183
TI  - E6AP mediates regulated proteasomal degradation of the nuclear receptor
      coactivator amplified in breast cancer 1 in immortalized cells.
AB  - The steroid receptor coactivator oncogene, amplified in breast cancer 1 (AIB1;
      also known as ACTR/RAC-3/TRAM-1/SRC-3/p/CIP), is amplified and overexpressed in a
      variety of epithelial tumors. AIB1 has been reported to have roles in both
      steroid-dependent and steroid-independent transcription during tumor progression.
      In this report, we describe that the cellular levels of AIB1 are controlled
      through regulated proteasomal degradation. We found that serum withdrawal or
      growth in high cell density caused rapid degradation of AIB1 protein, but not
      mRNA, in immortalized cell lines. Proteasome inhibitors prevented this process,
      and high molecular weight ubiquitylated species of AIB1 were detected. Nuclear
      export was required for proteasomal degradation of AIB1 and involved the
      ubiquitin ligase, E6AP. AIB1/E6AP complexes were detected in cellular extracts,
      and reduction of cellular E6AP levels with E6AP short interfering RNA prevented
      proteasomal degradation of AIB1. Conversely, overexpression of E6AP promoted AIB1
      degradation. The COOH terminus of AIB1 interacted with E6AP in vitro and deletion
      of this region in AIB1 rendered it resistant to degradation in cells. From our
      results, we propose a model whereby signals promoted by changes in the cellular
      milieu initiate E6AP-mediated proteasomal degradation of AIB1 and thus contribute
      to the control of steady-state levels of this protein.

PMID- 16951184
TI  - Mimp, a mitochondrial carrier homologue, inhibits Met-HGF/SF-induced scattering
      and tumorigenicity by altering Met-HGF/SF signaling pathways.
AB  - We have recently shown that Mimp, a mitochondrial carrier protein homologue, is
      induced by Met-hepatocyte growth factor/scatter factor (HGF/SF) signaling and
      decreases the mitochondrial membrane potential in DA3 mammary adenocarcinoma
      cells. We show here that induction of Mimp leads to growth arrest in response to
      HGF/SF by arresting cells at the S phase of the cell cycle. Induction of Mimp or
      its transient expression does not lead to apoptosis. Mimp also attenuates HGF/SF
      induced cellular scattering in vitro and tumor growth in vivo. The exogenous
      induction of Mimp at levels similar to its endogenous induction by HGF/SF
      increases the level of the Met protein and its phosphorylation by HGF/SF but
      reduces the levels of Shc and prevents the HGF/SF-induced tyrosine
      phosphorylation of Grb2 and Shc. In contrast, the level of phosphatidylinositol 3
      kinase (PI3K) increases following Mimp induction and the level of phosphorylated
      PI3K in response to HGF/SF is unaffected by the exogenous induction of Mimp.
      Moreover, exogenous Mimp prevents the HGF/SF-induced transcription of the serum
      response element-luciferase reporter gene. Our results show that Mimp expression
      reduces Met-HGF/SF-induced proliferation and scattering by attenuating and
      altering the downstream signaling of Met. These data show a new link between a
      tyrosine kinase growth factor receptor and a mitochondrial carrier homologue that
      regulates cellular growth, motility, and tumorigenicity.

PMID- 16951185
TI  - Antiangiogenic effect of TW37, a small-molecule inhibitor of Bcl-2.
AB  - Bcl-2 is an antiapoptotic protein that is up-regulated in several tumor types,
      and its expression levels have strong correlation to development of resistance to
      therapy and poor prognosis. We have shown recently that Bcl-2 also functions as a
      proangiogenic signaling molecule that activates a nuclear factor-kappaB-mediated
      pathway resulting in up-regulation of the angiogenic chemokines CXCL1 and CXCL8
      by neovascular endothelial cells. Here, we evaluate the antiangiogenic effect of
      the novel small-molecule inhibitor of Bcl-2 (TW37) developed using a structure
      based design strategy. We observed that TW37 has an IC(50) of 1.8 mumol/L for
      endothelial cells but showed no cytotoxic effects for fibroblasts at
      concentrations up to 50 mumol/L. The mechanism of TW37-induced endothelial cell
      death was apoptosis, in a process mediated by mitochondrial depolarization and
      activation of caspase-9 and caspase-3. The effect of TW37 on endothelial cell
      apoptosis was not prevented by coexposure to the growth factor milieu secreted by
      tumor cells. Inhibition of the angiogenic potential of endothelial cells (i.e.,
      migration and capillary sprouting assays) and expression of the angiogenic
      chemokines CXCL1 and CXCL8 were accomplished at subapoptotic TW37 concentrations
      (0.005-0.05 micromol/L). Notably, administration of TW37 i.v. resulted in a
      decrease in the density of functional human microvessels in the severe combined
      immunodeficient mouse model of human angiogenesis. In conclusion, we describe
      functionally separate proapoptotic and antiangiogenic mechanisms for a small
      molecule inhibitor of Bcl-2 and show the potential for Bcl-2 inhibition as a
      target for antiangiogenic therapy.

PMID- 16951186
TI  - Breast cancer growth prevention by statins.
AB  - Statins are cholesterol-lowering drugs with pleiotropic activities including
      inhibition of isoprenylation reactions and reduction of signals driving cell
      proliferation and survival responses. The objectives of this study were to
      examine the effects of statins on breast cancer cells, both in vitro and in vivo,
      and to begin to determine their mechanism of action. We evaluated the effects of
      statins on breast cancer cell growth, phosphoprotein signaling intermediates,
      survival/apoptosis regulators, cell cycle regulators, and activated transcription
      factors. We also examined the in vivo effect of statin administration in a mouse
      ErbB2(+) breast cancer model. Only lipophilic statins had direct anticancer
      activity in vitro. Breast cancer cells with activated Ras or ErbB2 pathways
      seemed to be more sensitive than those overexpressing estrogen receptor, and this
      correlated with endogenous levels of activated nuclear factor kappaB (NF-kappaB).
      Key intermediates regulating cell survival by NF-kappaB activation, as well as
      cell proliferation by the mitogen activated protein kinase cascade, were among
      the earliest phosphoproteins influenced by statin treatment. These early effects
      were followed by declines in activator protein-1 and NF-kappaB activation and
      concordant changes in other mediators of proliferation and apoptosis. In vivo
      results showed that oral dosing of statins significantly inhibited the growth of
      a mouse mammary carcinoma. Lipophilic statins can exert direct anticancer
      activity in vitro by reducing proliferation and survival signals in susceptible
      breast cancer phenotypes. Tumor growth inhibition in vivo using a clinically
      relevant statin dose also seems to be associated with reduced tumor cell
      proliferation and survival. These findings provide supporting rationale for
      future statin trials in breast cancer patients.

PMID- 16951187
TI  - AMG 706, an oral, multikinase inhibitor that selectively targets vascular
      endothelial growth factor, platelet-derived growth factor, and kit receptors,
      potently inhibits angiogenesis and induces regression in tumor xenografts.
AB  - The growth of solid tumors is dependent on the continued stimulation of
      endothelial cell proliferation and migration resulting in angiogenesis. The
      angiogenic process is controlled by a variety of factors of which the vascular
      endothelial growth factor (VEGF) pathway and its receptors play a pivotal role.
      Small-molecule inhibitors of VEGF receptors (VEGFR) have been shown to inhibit
      angiogenesis and tumor growth in preclinical models and in clinical trials. A
      novel nicotinamide, AMG 706, was identified as a potent, orally bioavailable
      inhibitor of the VEGFR1/Flt1, VEGFR2/kinase domain receptor/Flk-1, VEGFR3/Flt4,
      platelet-derived growth factor receptor, and Kit receptors in preclinical models.
      AMG 706 inhibited human endothelial cell proliferation induced by VEGF, but not
      by basic fibroblast growth factor in vitro, as well as vascular permeability
      induced by VEGF in mice. Oral administration of AMG 706 potently inhibited VEGF
      induced angiogenesis in the rat corneal model and induced regression of
      established A431 xenografts. AMG 706 was well tolerated and had no significant
      effects on body weight or on the general health of the animals. Histologic
      analysis of tumor xenografts from AMG 706-treated animals revealed an increase in
      endothelial apoptosis and a reduction in blood vessel area that preceded an
      increase in tumor cell apoptosis. In summary, AMG 706 is an orally bioavailable,
      well-tolerated multikinase inhibitor that is presently under clinical
      investigation for the treatment of human malignancies.

PMID- 16951188
TI  - AAL881, a novel small molecule inhibitor of RAF and vascular endothelial growth
      factor receptor activities, blocks the growth of malignant glioma.
AB  - Malignant gliomas are highly proliferative and angiogenic cancers resistant to
      conventional therapies. Although RAS and RAF mutations are uncommon in gliomas,
      RAS activity is increased in gliomas. Additionally, vascular endothelial growth
      factor and its cognate receptors are highly expressed in gliomas. We now report
      that AAL881, a novel low-molecular weight inhibitor of the kinase activities
      associated with B-RAF, C-RAF (RAF-1), and VEGF receptor-2 (VEGFR2), showed
      activity against glioma cell lines and xenografts. In culture, AAL881 inhibited
      the downstream effectors of RAF in a concentration-dependent manner, with
      inhibition of proliferation associated with a G(1) cell cycle arrest, induction
      of apoptosis, and decreased colony formation. AAL881 decreased the proliferation
      of bovine aortic endothelial cells as well as the tumor cell secretion of
      vascular endothelial growth factor and inhibited the invasion of glioma cells
      through an artificial extracellular matrix. Orally administered AAL881 was well
      tolerated with minimal weight loss in non-tumor-bearing mice. Established s.c.
      human malignant glioma xenografts grown in immunocompromised mice treated with a
      10-day course of oral AAL881 exhibited growth delays relative to control tumors,
      frequently resulting in long-term complete regressions. AAL881 treatment extended
      the survival of immunocompromised mice bearing orthotopic glioma xenografts
      compared with placebo controls. The intraparenchymal portions of orthotopic
      AAL881-treated tumors underwent widespread necrosis consistent with vascular
      disruption compared with the subarachnoid elements. These effects are distinct
      from our prior experience with VEGFR2 inhibitors, suggesting that targeting RAF
      itself or in combination with VEGFR2 induces profound tumor responses in gliomas
      and may serve as a novel therapeutic approach in patients with malignant gliomas.

PMID- 16951189
TI  - A small-molecule inhibitor of Bcl-XL potentiates the activity of cytotoxic drugs
      in vitro and in vivo.
AB  - Inhibition of the prosurvival members of the Bcl-2 family of proteins represents
      an attractive strategy for the treatment of cancer. We have previously reported
      the activity of ABT-737, a potent inhibitor of Bcl-2, Bcl-X(L), and Bcl-w, which
      exhibits monotherapy efficacy in xenograft models of small-cell lung cancer and
      lymphoma and potentiates the activity of numerous cytotoxic agents. Here we
      describe the biological activity of A-385358, a small molecule with relative
      selectivity for binding to Bcl-X(L) versus Bcl-2 (K(i)'s of 0.80 and 67 nmol/L
      for Bcl-X(L) and Bcl-2, respectively). This compound efficiently enters cells and
      co-localizes with the mitochondrial membrane. Although A-385358 shows relatively
      modest single-agent cytotoxic activity against most tumor cell lines, it has an
      EC(50) of <500 nmol/L in cells dependent on Bcl-X(L) for survival. In addition, A
      385358 enhances the in vitro cytotoxic activity of numerous chemotherapeutic
      agents (paclitaxel, etoposide, cisplatin, and doxorubicin) in several tumor cell
      lines. In A549 non-small-cell lung cancer cells, A-385358 potentiates the
      activity of paclitaxel by as much as 25-fold. Importantly, A-385358 also
      potentiated the activity of paclitaxel in vivo. Significant inhibition of tumor
      growth was observed when A-385358 was added to maximally tolerated or half
      maximally tolerated doses of paclitaxel in the A549 xenograft model. In tumors,
      the combination therapy also resulted in a significant increase in mitotic arrest
      followed by apoptosis relative to paclitaxel monotherapy.

PMID- 16951190
TI  - A carbohydrate recognition-based drug delivery and controlled release system
      using intraperitoneal macrophages as a cellular vehicle.
AB  - The lymphoid tissue in the omentum, at the so-called milky spots, is known as an
      initial place for disseminated cancer cells to develop into solid tumors. In the
      present study, i.p. macrophages significantly took up oligomannose-coated
      liposomes (OMLs) that were injected into the peritoneal cavity, and then
      gradually accumulated in the omentum and the other lymphoid tissues within 24
      hours of i.p. injection of OMLs. When 5-fluorouracil (5-FU) was encapsulated in
      the OMLs, >60% of administered 5-FU accumulated in the omentum. Treatment of
      macrophages at 39 degrees C for 30 minutes led to the release of 5-FU from the
      macrophages, suggesting that controlled release from macrophages could be
      achieved by mild hyperthermia. We encased magnetic nanoparticles, which are known
      to convert electromagnetic energy to heat in the OMLs to achieve in vivo
      hyperthermia at the site. Using this system in a mouse i.p. metastasis model, we
      successfully controlled tumor development by coadministration of OML-encased 5-FU
      and OML-encased magnetic nanoparticles, followed by treatment with an alternating
      magnetic field. No apparent reduction was seen in tumor growth with the
      administration of OML-encased magnetic nanoparticles or OML-encased 5-FU alone.
      Thus, we have established the use of i.p. macrophages as a novel drug delivery
      system for the control of cancer metastatic to milky spots.

PMID- 16951191
TI  - Agonist and antagonist of retinoic acid receptors cause similar changes in gene
      expression and induce senescence-like growth arrest in MCF-7 breast carcinoma
      cells.
AB  - Biological effects of retinoids are mediated via retinoic acid (RA) receptors
      (RAR) and retinoid X receptors (RXR). The best-characterized mechanism of
      retinoid action is stimulation of transcription from promoters containing RA
      response elements (RARE). Retinoids induce senescence-like growth arrest in MCF-7
      breast carcinoma cells; this effect is associated with the induction of several
      growth-inhibitory genes. We have now found that these genes are induced by RAR
      specific but not by RXR-specific ligands. Genome-scale microarray analysis of
      gene expression was used to compare the effects of two pan-RAR ligands, one of
      which is a strong agonist of RARE-dependent transcription, whereas the other
      induces such transcription only weakly and antagonizes the inducing effect of RAR
      agonists. Both RAR ligands, however, produced very similar effects on gene
      expression in MCF-7 cells, suggesting that RARE-dependent transcription is only a
      minor component of retinoid-induced changes in gene expression. The effects of
      RAR ligands on gene expression parallel changes associated with damage-induced
      senescence, and both ligands induced G(1) arrest and the senescent phenotype in
      MCF-7 cells. The RAR ligands up-regulated many tumor-suppressive genes and down
      regulated multiple genes with oncogenic activities. Genes that are strongly
      induced by RAR ligands encode secreted bioactive proteins, including several
      tumor-suppressing factors. In agreement with these observations, retinoid-treated
      MCF-7 cells inhibited the growth of retinoid-insensitive MDA-MB-231 breast
      carcinoma cells in coculture. These results indicate that RARE-independent
      transcriptional effects of RAR ligands lead to senescence-like growth arrest and
      paracrine growth-inhibitory activity in MCF-7 breast carcinoma cells.

PMID- 16951192
TI  - Valproic acid enhances the efficacy of chemotherapy in EBV-positive tumors by
      increasing lytic viral gene expression.
AB  - EBV infection in tumor cells is generally restricted to the latent forms of viral
      infection. Switching the latent form of viral infection into the lytic form may
      induce tumor cell death. We have previously reported that certain chemotherapy
      agents can increase the amount of lytic viral gene expression in EBV-positive
      tumor cells. In this report, we have explored the potential utility of valproic
      acid (VPA), an anti-seizure drug that also has strong histone deacetylase
      inhibitory activity, for activating lytic viral gene expression in EBV-positive
      tumors. Although VPA treatment alone induced only a modest increase in the level
      of lytic viral gene expression, it strongly enhanced the ability of
      chemotherapeutic agents to induce lytic EBV gene expression in EBV-positive
      epithelial and lymphoid cells in vitro. Furthermore, VPA enhanced cell killing in
      vitro by chemotherapeutic agents in lymphoblastoid cells and gastric cells (AGS)
      containing wild-type EBV. In contrast, VPA did not enhance the cytotoxicity of
      chemotherapy in lymphoblastoid cells containing a lytic-defective (BZLF1
      knockout) form of EBV or in EBV-negative AGS cells. Finally, we found that the
      combination of VPA and chemotherapy was significantly more effective in
      inhibiting EBV-driven lymphoproliferative disease in severe combined
      immunodeficient mice than chemotherapy alone. These results suggest that VPA
      could potentiate the efficacy of chemotherapy for EBV-positive tumors in
      patients.

PMID- 16951193
TI  - Vascular endothelial growth factor overexpression by soft tissue sarcoma cells:
      implications for tumor growth, metastasis, and chemoresistance.
AB  - To better elucidate the role of vascular endothelial growth factor (VEGF)(165) in
      soft tissue sarcoma (STS) growth, metastasis, and chemoresistance, we generated
      stably transfected human STS cell lines with VEGF(165) to study the effect of
      VEGF(165) on STS cells in vitro and the effect of culture medium from these cells
      on human umbilical vascular endothelial cells. Severe combined immunodeficient
      mice bearing xenografts of transfected cell lines were used to assess the effect
      of VEGF overexpression and the effect of VEGF receptor (VEGFR) 2 inhibition on
      STS growth, metastasis, and response to doxorubicin. VEGF(165)-transfected
      xenografts formed highly vascular tumors with shorter latency, accelerated
      growth, enhanced chemoresistance, and increased incidence of pulmonary
      metastases. Blockade of VEGFR2 signaling using DC101 anti-VEGFR2 monoclonal
      antibody enhanced doxorubicin chemoresponse; this combined biochemotherapy
      inhibited tumor growth and decreased pulmonary metastases without overt toxicity.
      Combined therapy reduced microvessel counts while increasing vessel maturation
      index. VEGF overexpression did not affect on the sarcoma cells per se; however,
      conditioned medium from VEGF transfectants caused increased endothelial cell
      proliferation, migration, and chemoresistance. Addition of DC101 induced
      endothelial cell sensitivity to doxorubicin and suppressed the activity of matrix
      metalloproteinases secreted by endothelial cells. We therefore conclude that VEGF
      is a critical determinant of STS growth and metastasis and that STS
      chemoresistance, in our model, is a process induced by the interplay between STS
      cells and tumor-associated endothelial cells. STS growth and metastasis can be
      interrupted by combined low-dose doxorubicin and anti-VEGFR2, a strategy that
      attacks STS-associated endothelial cells. In the future, such therapeutic
      approaches may be useful in treating STS before the development of clinically
      apparent metastases.

PMID- 16951194
TI  - Oligomannurarate sulfate, a novel heparanase inhibitor simultaneously targeting
      basic fibroblast growth factor, combats tumor angiogenesis and metastasis.
AB  - Inhibitors of tumor angiogenesis and metastasis are increasingly emerging as
      promising agents for cancer therapy. Recently, heparanase inhibitors have offered
      a new avenue for such work because heparanase is thought to be critically
      involved in the metastatic and angiogenic potentials of tumor cells. Here, we
      report that oligomannurarate sulfate (JG3), a novel marine-derived
      oligosaccharide, acts as a heparanase inhibitor. Our results revealed that JG3
      significantly inhibited tumor angiogenesis and metastasis, both in vitro and in
      vivo, by combating heparanase activity via binding to the KKDC and QPLK domains
      of the heparanase molecule. The JG3-heparanase interaction was competitively
      inhibited by low molecular weight heparin (4,000 Da) but not by other
      glycosaminoglycans. In addition, JG3 abolished heparanase-driven invasion,
      inhibited the release of heparan sulfate-sequestered basic fibroblast growth
      factor (bFGF) from the extracellular matrix, and repressed subsequent
      angiogenesis. Moreover, JG3 inactivated bFGF-induced bFGF receptor and
      extracellular signal-regulated kinase 1/2 phosphorylation and blocked bFGF
      triggered angiogenic events by directly binding to bFGF. Thus, JG3 seems to
      inhibit both major heparanase activities by simultaneously acting as a substrate
      mimetic and as a competitive inhibitor of heparan sulfate. These findings suggest
      that JG3 should be considered as a promising candidate agent for cancer therapy.

PMID- 16951195
TI  - Overexpression of tissue transglutaminase leads to constitutive activation of
      nuclear factor-kappaB in cancer cells: delineation of a novel pathway.
AB  - The transcription factor nuclear factor-kappaB (NF-kappaB) plays an important
      role in regulating cell growth, apoptosis, and metastatic functions. Constitutive
      activation of NF-kappaB has been observed in various cancers; however, molecular
      mechanisms resulting in such activation remain elusive. Based on our previous
      results showing that drug-resistant and metastatic cancer cells have high levels
      of tissue transglutaminase (TG2) expression and that this expression can confer
      chemoresistance to certain types of cancer cells, we hypothesized that TG2
      contributes to constitutive activation of NF-kappaB. Numerous lines of evidence
      showed that overexpression of TG2 is linked with constitutive activation of NF
      kappaB. Tumor cells with overexpression of TG2 exhibited increased levels of
      constitutively active NF-kappaB. Activation of TG2 led to activation of NF
      kappaB; conversely, inhibition of TG2 activity inhibited activation of NF-kappaB.
      Similarly, ectopic expression of TG2 caused activation of NF-kappaB, and
      inhibition of expression of TG2 by small interfering RNA abolished the activation
      of NF-kappaB. Our results further indicated that constitutive NF-kappaB reporter
      activity in pancreatic cancer cells is not affected by dominant-negative I kappaB
      alpha. Additionally, coimmunoprecipitation and confocal microscopy showed that I
      kappaB alpha is physically associated with TG2. Lastly, immunohistochemical
      analysis of pancreatic ductal carcinoma samples obtained from 61 patients further
      supported a strong correlation between TG2 expression and NF-kappaB
      activation/overexpression (P = 0.0098, Fisher's exact test). We conclude that TG2
      induces constitutive activation of NF-kappaB in tumor cells via a novel pathway
      that is most likely independent of I kappaB alpha kinase. Therefore, TG2 may be
      an attractive alternate target for inhibiting constitutive NF-kappaB activation
      and rendering cancer cells sensitive to anticancer therapies.

PMID- 16951196
TI  - Pituitary adenylate cyclase-activating polypeptide is a potent inhibitor of the
      growth of light chain-secreting human multiple myeloma cells.
AB  - Multiple myeloma represents a malignant proliferation of plasma cells in the bone
      marrow, which often overproduces immunoglobulin light chains. We have shown
      previously that pituitary adenylate cyclase-activating polypeptide (PACAP)
      markedly suppresses the release of proinflammatory cytokines from light chain
      stimulated human renal proximal tubule epithelial cells and prevents the
      resulting tubule cell injury. In this study, we have shown that PACAP suppresses
      the proliferation of human kappa and lambda light chain-secreting multiple
      myeloma-derived cells. The addition of PACAP suppressed light chain-producing
      myeloma cell-stimulated interleukin 6 (IL-6) secretion by the bone marrow stromal
      cells (BMSCs). A specific antagonist to either the human PACAP-specific receptor
      or the vasoactive intestinal peptide receptor attenuated the suppressive effect
      of PACAP on IL-6 production in the adhesion of human multiple myeloma cells to
      BMSCs. The secretion of IL-6 by BMSCs was completely inhibited by 10(-9) mol/L
      PACAP, which also attenuated the phosphorylation of both p42/44 and p38 mitogen
      activated protein kinases (MAPK) as well as nuclear factor-kappaB (NF-kappaB)
      activation in response to the adhesion of multiple myeloma cells to BMSCs,
      whereas the inhibition of p42/44 MAPK signaling attenuated PACAP action. The
      signaling cascades involved in the inhibitory effect of PACAP on IL-6-mediated
      paracrine stimulation of light chain-secreting myeloma cell growth was mediated
      through the suppression of p38 MAPK as well as modulation of activation of
      transcription factor NF-kappaB. These findings suggest that PACAP may be a new
      antitumor agent that directly suppresses light chain-secreting myeloma cell
      growth and indirectly affects tumor cell growth by modifying the bone marrow
      milieu of the multiple myeloma.

PMID- 16951197
TI  - Mechanism of action of sulforaphane: inhibition of p38 mitogen-activated protein
      kinase isoforms contributing to the induction of antioxidant response element
      mediated heme oxygenase-1 in human hepatoma HepG2 cells.
AB  - Exposure of sulforaphane to HepG2 cells increased heme oxygenase-1 (HO-1)
      expression by activating antioxidant response element (ARE) through induction of
      Nrf2 and suppression of Kelch-like ECH-associated protein 1 (Keap1). Using human
      HO-1 promoter reporter plasmids and ChIP assay, we have identified that
      sulforaphane transcriptionally activated the upstream ARE-rich enhancer region,
      located at -9.0 kb upstream human HO-1 promoter. Induction of HO-1 by
      sulforaphane was attenuated by overexpression of mutant Nrf2 plasmid in HepG2
      cells and totally abolished in Nrf2 knockout mouse embryonic keratinocytes and
      fibroblasts. Overexpression of individual p38 mitogen-activated protein (MAP)
      kinase (MAPK) isoforms also suppressed constitutive as well as sulforaphane- or
      Nrf2-induced ARE-dependent gene expression. Among the upstream kinases, although
      MKK3 was not involved in suppression of ARE by any of p38 MAPK isoforms, MKK6
      selectively suppressed ARE by p38 gamma or p38 delta, but not by p38 alpha or p38
      beta. Importantly, sulforaphane not only activated MAP/extracellular signal
      regulated kinase (ERK) kinases 1/2 and ERK1/2, but also strongly suppressed
      anisomycin-induced activation of p38 MAPK isoforms by blocking phosphorylation of
      upstream kinases, MKK3/6. Finally, we found that stimulation of p38 MAPK isoforms
      phosphorylated purified Nrf2 protein and caused an increase in the interaction
      between Nrf2 and Keap1 in vitro and the suppression of Nrf2 translocation into
      the nucleus. Collectively, our results indicate that transcriptional activation
      of Nrf2/ARE is critical in sulforaphane-mediated induction of HO-1, which can be
      modulated in part by the blockade of p38 MAPK signaling pathway. In addition, our
      study shows that p38 MAPK can phosphorylate Nrf2 and promotes the association
      between Nrf2 and Keap1 proteins, thereby potentially inhibiting nuclear
      translocation of Nrf2.

PMID- 16951198
TI  - Class II histone deacetylases are associated with VHL-independent regulation of
      hypoxia-inducible factor 1 alpha.
AB  - Hypoxia-inducible factor 1 alpha (HIF-1 alpha) plays a critical role in
      transcriptional gene activation involved in tumor angiogenesis. A novel class of
      agents, the histone deacetylase (HDAC) inhibitors, has been shown to inhibit
      tumor angiogenesis and HIF-1 alpha protein expression. However, the molecular
      mechanism responsible for this inhibition remains to be elucidated. In the
      current study, we investigated the molecular link between HIF-1 alpha inhibition
      and HDAC inhibition. Treatment of the VHL-deficient human renal cell carcinoma
      cell line UMRC2 with the hydroxamic HDAC inhibitor LAQ824 resulted in a dose
      dependent inhibition of HIF-1 alpha protein via a VHL-independent mechanism and
      reduction of HIF-1 alpha transcriptional activity. HIF-1 alpha inhibition by
      LAQ824 was associated with HIF-1 alpha acetylation and polyubiquitination. HIF-1
      alpha immunoprecipitates contained HDAC activity. Then, we tested different
      classes of HDAC inhibitors with diverse inhibitory activity of class I versus
      class II HDACs and assessed their capability of targeting HIF-1 alpha. Hydroxamic
      acid derivatives with known activity against both class I and class II HDACs were
      effective in inhibiting HIF-1 alpha at low nanomolar concentrations. In contrast,
      valproic acid and trapoxin were able to inhibit HIF-1 alpha only at
      concentrations that are effective against class II HDACs. Coimmunoprecipitation
      studies showed that class II HDAC4 and HDAC6 were associated with HIF-1 alpha
      protein. Inhibition by small interfering RNA of HDAC4 and HDAC6 reduced HIF-1
      alpha protein expression and transcriptional activity. Taken together, these
      results suggest that class II HDACs are associated with HIF-1 alpha stability and
      provide a rationale for targeting HIF-1 alpha with HDAC inhibitors against class
      II isozymes.

PMID- 16951199
TI  - Mechanism of increased coxsackie and adenovirus receptor gene expression and
      adenovirus uptake by phytoestrogen and histone deacetylase inhibitor in human
      bladder cancer cells and the potential clinical application.
AB  - Coxsackie and adenovirus receptor (CAR) is known as a principal receptor for
      adenovirus commonly used as a gene delivery vector. Down-regulation of CAR is
      often detected in several cancer types. Epigenetic modifiers such as histone
      deacetylase inhibitor FK228 (depsipeptide) have been shown to increase CAR
      expression as well as the uptake of adenovirus in bladder cancer in vivo and in
      vitro, indicating that altered transcriptional regulation of CAR is the key
      mechanism responsible for the decreased CAR levels in this cancer. In this study,
      we screened agents that could induce CAR expression in bladder cancer cells.
      Fifty-eight drugs with various chemical properties were tested. Ipriflavone and
      plant isoflavones were found to exhibit the ability to induce CAR gene expression
      in combination with FK228. Genistein, the natural isoflavone found in soybean,
      when combined with FK228, exerts a synergistic effect on CAR gene and protein
      expression in bladder cancer cells. Chromatin immunoprecipitation results showed
      an increased histone acetylation in the CAR promoter gene, which is due to the
      suppression of histone deacetylase activity by both agents. Also, our data
      indicated that combination treatment is a potent chemotherapeutic regimen for
      bladder cancer cells and the subsequent administration of recombinant adenovirus
      could further eliminate the remaining cells. Taken together, our results provide
      a strong rationale for combining chemotherapeutic and gene therapeutic agents to
      enhance the therapeutic efficacy in bladder cancer.

PMID- 16951200
TI  - Fluorodeoxyuridine modulates cellular expression of the DNA base excision repair
      enzyme uracil-DNA glycosylase.
AB  - The thymidylate synthase inhibitor 5-fluorouracil (5-FU) continues to play a
      pivotal role in the treatment of cancer. A downstream event of thymidylate
      synthase inhibition involves the induction of a self-defeating base excision
      repair process. With the depletion of TTP pools, there is also an increase in
      dUMP. Metabolism of dUMP to the triphosphate dUTP results in elevated pools of
      this atypical precursor for DNA synthesis. Under these conditions, there is a
      destructive cycle of dUMP incorporation into DNA, removal of uracil by the base
      excision repair enzyme uracil-DNA glycosylase (UDG), and reincorporation of dUMP
      during the synthesis phase of DNA repair. The end point is DNA strand breaks and
      loss of DNA integrity, which contributes to cell death. Evidence presented here
      indicates that both the nuclear and the mitochondrial isoforms of UDG are
      modulated by FdUrd (and 5-FU) treatment in certain cell lines but not in others.
      Modulation occurs at the transcriptional and post-translational levels. Under
      normal conditions, nUDG protein appears in G(1) and is degraded during the S to
      G(2) phase transition. The present study provides evidence that, in certain cell
      lines, FdUrd mediates an atypical turnover of nUDG. Additional data indicate
      that, for cell lines that do not down-regulate nUDG, small interfering RNA
      mediated knockdown of nUDG significantly increases resistance to the cytotoxic
      effects of FdUrd. Results from these studies show that nUDG is an additional
      determinant in FdUrd-mediated cytotoxicity and bolster the notion that the self
      defeating base excision repair pathway, instigated by elevated dUTP (FdUTP)
      pools, contributes to the cytotoxic consequences of 5-FU chemotherapy.

PMID- 16951201
TI  - Farnesyltransferase inhibitors reverse taxane resistance.
AB  - The combination of farnesyltransferase inhibitors (FTIs) and taxanes has been
      shown to result in potent antiproliferative and antimitotic synergy. Recent phase
      I and II clinical trials have shown that this combination shows clinical activity
      in taxane-refractory or taxane-resistant cancer patients. To understand the
      mechanism behind these clinical observations, we used a cancer cell model of
      paclitaxel resistance and showed that the FTI/taxane combination retains potent
      antiproliferative, antimitotic, and proapoptotic activity against the paclitaxel
      resistant cells, at doses where each drug alone has little or no activity. To
      probe the mechanistic basis of these observations, paclitaxel activity was
      monitored in living cells using the fluorescently conjugated paclitaxel, Flutax
      2. We observed that all FTIs tested increase the amount of microtubule-bound
      Flutax-2 and the number of microtubules labeled with Flutax-2 in both paclitaxel
      resistant and paclitaxel-sensitive cells. Importantly, we observed a
      consequential increase in microtubule stability and tubulin acetylation with the
      combination of the two drugs, even in paclitaxel-resistant cells, confirming that
      the enhanced taxane binding in the presence of FTI affects microtubule function.
      Furthermore, this mechanism is dependent on the function of the tubulin
      deacetylase, HDAC6, because in cells overexpressing a catalytically inactive
      HDAC6, FTIs are incapable of enhancing Flutax-2-microtubule binding. Similar
      results were obtained by using an FTI devoid of farnesyltransferase inhibitory
      activity, indicating that functional inhibition of farnesyltransferase is also
      required. Overall, these studies provide a new insight into the functional
      relationship between HDAC6, farnesyltransferase, and microtubules, and support
      clinical data showing that the FTI/taxane combination is effective in taxane
      refractory patients.

PMID- 16951203
TI  - Flavopiridol induces cellular FLICE-inhibitory protein degradation by the
      proteasome and promotes TRAIL-induced early signaling and apoptosis in breast
      tumor cells.
AB  - The cyclin-dependent kinase inhibitor flavopiridol is undergoing clinical trials
      as an antitumor drug. We show here that pretreatment of different human breast
      cancer cell lines with flavopiridol facilitates tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL)-induced apoptosis. In breast tumor cells,
      apoptosis induction by TRAIL is blocked at the level of apical caspase-8
      activation. Flavopiridol treatment enhances TRAIL-induced formation of death
      inducing signaling complex and early processing of procaspase-8. Subsequently, a
      TRAIL-induced, mitochondria-operated pathway of apoptosis is activated in cells
      treated with flavopiridol. Down-regulation of cellular FLICE-inhibitory proteins
      (c-FLIP; c-FLIP(L) and c-FLIP(S)) is observed on flavopiridol treatment. c-FLIP
      loss and apoptosis sensitization by flavopiridol are both prevented in cells
      treated with an inhibitor of the ubiquitin-proteasome system. Furthermore,
      targeting c-FLIP directly with small interfering RNA oligonucleotides also
      sensitizes various human breast tumor cell lines to TRAIL-induced apoptosis. Our
      results indicate that flavopiridol sensitizes breast cancer cells to TRAIL
      induced apoptosis by facilitating early events in the apoptotic pathway, and this
      combination treatment could be regarded as a potential therapeutic tool against
      breast tumors.

PMID- 16951202
TI  - Organic cation transporters are determinants of oxaliplatin cytotoxicity.
AB  - Although the platinum-based anticancer drugs cisplatin, carboplatin, and
      oxaliplatin have similar DNA-binding properties, only oxaliplatin is active
      against colorectal tumors. The mechanisms for this tumor specificity of platinum
      based compounds are poorly understood but could be related to differences in
      uptake. This study shows that the human organic cation transporters (OCT) 1 and 2
      (SLC22A1 and SLC22A2) markedly increase oxaliplatin, but not cisplatin or
      carboplatin, accumulation and cytotoxicity in transfected cells, indicating that
      oxaliplatin is an excellent substrate of these transporters. The cytotoxicity of
      oxaliplatin was greater than that of cisplatin in six colon cancer cell lines
      [mean +/- SE of IC(50) in the six cell lines, 3.9 +/- 1.4 micromol/L
      (oxaliplatin) versus 11 +/- 2.0 micromol/L (cisplatin)] but was reduced by an OCT
      inhibitor, cimetidine, to a level similar to, or even lower than that of,
      cisplatin (29 +/- 11 micromol/L for oxaliplatin versus 19 +/- 4.3 micromol/L for
      cisplatin). Structure-activity studies indicated that organic functionalities on
      nonleaving groups coordinated to platinum are critical for selective uptake by
      OCTs. These results indicate that OCT1 and OCT2 are major determinants of the
      anticancer activity of oxaliplatin and may contribute to its antitumor
      specificity. They also strongly suggest that expression of OCTs in tumors should
      be investigated as markers for selecting specific platinum-based therapies in
      individual patients. The development of new anticancer drugs, specifically
      targeted to OCTs, represents a novel strategy for targeted drug therapy. The
      results of the present structure-activity studies indicate specific tactics for
      realizing this goal.

PMID- 16951204
TI  - Mitogen-activated protein kinase phosphatase-1 is required for cisplatin
      resistance.
AB  - Mitogen-activated protein kinase (MAPK) phosphatase (MKP)-1 is a member of the
      MKP family that negatively regulates MAPK signaling. MKP-1 has been implicated in
      cell survival in response to stressful stimuli, including anticancer treatment,
      but its role in cisplatin resistance is not fully understood. Here, we show that
      cisplatin induces MKP-1 in several human cancer cell lines. Induction of MKP-1 by
      cisplatin was through the transcriptional mechanism regulated by extracellular
      signal-regulated kinase (ERK). Overexpression of MKP-1 rendered human lung cancer
      cells resistant to cisplatin. Conversely, down-regulation of MKP-1 by small
      interfering RNA silencing sensitized human lung cancer cells to cisplatin-induced
      cell death. Using primary mouse embryonic fibroblasts (MEF) from MKP-1 knockout
      mice, we show that induction of MKP-1 by cisplatin correlates with inactivation
      of c-Jun NH(2)-terminal kinase (JNK) but not ERK and p38. Furthermore, apoptosis
      induced by cisplatin was significant in MKP-1(-/-) MEFs, whereas such change was
      minimal in MKP-1(+/+) MEFs. More importantly, cisplatin-induced cell death is
      inhibited by blocking JNK but not ERK and p38 activities. Collectively, our
      results establish a critical role of JNK in cisplatin-induced apoptosis and
      suggest that MKP-1 is required for cisplatin resistance.

PMID- 16951205
TI  - Enhanced antitumor activity of murine-human hybrid T-cell receptor (TCR) in human
      lymphocytes is associated with improved pairing and TCR/CD3 stability.
AB  - Little is known about the biology of murine T-cell receptors (TCR) expressed in
      human cells. We recently observed that a murine anti-human p53 TCR is highly
      functional when expressed in human lymphocytes. Herein, we compare human and
      mouse TCR function and expression to delineate the molecular basis for the
      apparent superior biological activity of murine receptors in human T lymphocytes.
      To this end, we created hybrid TCRs where we swapped the original constant
      regions with either human or mouse ones, respectively. We showed that murine or
      "murinized" receptors were overexpressed on the surface of human lymphocytes
      compared with their human/humanized counterparts and were able to mediate higher
      levels of cytokine secretion when cocultured with peptide-pulsed antigen
      presenting cells. Preferential pairing of murine constant regions and improved
      CD3 stability seemed to be responsible for these observations. These enhanced
      biological properties translated into significantly greater antitumor response
      mediated by TCR with mouse constant regions. Furthermore, we were able to
      circumvent the natural low avidity of class I MHC TCR in CD4(+) cells by
      introducing the murinized TCR into CD4(+) lymphocytes, giving them the ability to
      recognize melanoma tumors. These findings have implications for human TCR gene
      transfer therapy and may provide new insights into the biology of the TCR/CD3
      complex.

PMID- 16951206
TI  - Induction of potent antitumor immunity by intratumoral injection of interleukin
      23-transduced dendritic cells.
AB  - Dendritic cells (DCs) are potent antigen-presenting cells that play a critical
      role in priming immune responses to tumor. Interleukin (IL)-23 can act directly
      on DC to promote immunogenic presentation of tumor peptide in vitro. Here, we
      evaluated the combination of bone marrow-derived DC and IL-23 on the induction of
      antitumor immunity in a mouse intracranial glioma model. DCs can be transduced by
      an adenoviral vector coding single-chain mouse IL-23 to express high levels of
      bioactive IL-23. Intratumoral implantation of IL-23-expressing DCs produced a
      protective effect on intracranial tumor-bearing mice. The mice consequently
      gained systemic immunity against the same tumor rechallenge. The protective
      effect of IL-23-expressing DCs was comparable with or even better than that of IL
      12-expressing DCs. IL-23-transduced DC (DC-IL-23) treatment resulted in robust
      intratumoral CD8(+) and CD4(+) T-cell infiltration and induced a specific TH1
      type response to the tumor in regional lymph nodes and spleen at levels greater
      than those of nontransduced DCs. Moreover, splenocytes from animals treated with
      DC-IL-23 showed heightened levels of specific CTL activity. In vivo lymphocyte
      depletion experiments showed that the antitumor immunity induced by DC-IL-23 was
      mainly dependent on CD8(+) T cells and that CD4(+) T cells and natural killer
      cells were also involved. In summary, i.t. injection of DC-IL-23 resulted in
      significant and effective systemic antitumor immunity in intracranial tumor
      bearing mice. These findings suggest a new approach to induce potent tumor
      specific immunity to intracranial tumors. This approach may have therapeutic
      potential for treating human glioma.

PMID- 16951207
TI  - Susceptibility to induced and spontaneous carcinogenesis is increased in fatless
      A-ZIP/F-1 but not in obese ob/ob mice.
AB  - Obesity is typically associated with increased tumor susceptibility, whereas
      caloric restriction, a regimen resulting in leanness, inhibits carcinogenesis.
      The link between adiposity and malignancies suggests that adipose tissue may
      influence carcinogenesis. An adipose tissue hormone, leptin, could be
      procarcinogenic because it stimulates proliferation in various tissues and tumor
      cell lines. Leptin may contribute to the correlation between adiposity and
      malignancies as its levels are usually increased in obese subjects and reduced by
      caloric restriction. We hypothesized that leptin deficiency, despite obesity,
      would inhibit carcinogenesis in leptin-null ob/ob mice and tested this hypothesis
      in two models: (a) two-stage skin carcinogenesis initiated by 7,12
      dimethylbenz(a)anthracene and promoted by phorbol 12-myristate 13-acetate (PMA)
      and (b) p53 deficiency. Contrary to a typical association between obesity and
      enhanced carcinogenesis, obese ob/ob mice developed induced skin papillomas and
      spontaneous p53-deficient malignancies, mostly lymphomas, similarly to their lean
      littermates. Surprisingly, lipodystrophic (ZIP) mice that had very little both
      adipose tissue and leptin were highly susceptible to carcinogenesis. Hyperphagia,
      hyperinsulinemia, and hyperglycemia are unlikely to have contributed
      significantly to the enhancement of carcinogenesis in ZIP mice because similarly
      hyperphagic, hyperinsulinemic, and hyperglycemic ob/ob mice had normal
      susceptibility to carcinogenesis. Our data suggest that, in contrast to a well
      known correlation between obesity and cancer, the direct effect of adipose tissue
      may rather be protective.

PMID- 16951208
TI  - Sequential valproic acid/all-trans retinoic acid treatment reprograms
      differentiation in refractory and high-risk acute myeloid leukemia.
AB  - Epigenetic alterations of chromatin due to aberrant histone deacetylase (HDAC)
      activity and transcriptional silencing of all-trans retinoic acid (ATRA) pathway
      are events linked to the pathogenesis of acute myeloid leukemia (AML) that can be
      targeted by specific treatments. A pilot study was carried out in eight
      refractory or high-risk AML patients not eligible for intensive therapy to assess
      the biological and therapeutic activities of the HDAC inhibitor valproic acid
      (VPA) used to remodel chromatin, followed by the addition of ATRA, to activate
      gene transcription and differentiation in leukemic cells. Hyperacetylation of
      histones H3 and H4 was detectable at therapeutic VPA serum levels (>or=50
      microg/mL) in blood mononuclear cells from seven of eight patients. This
      correlated with myelomonocytic differentiation of leukemic cells as revealed by
      morphologic, cytochemical, immunophenotypic, and gene expression analyses.
      Differentiation of the leukemic clone was proven by fluorescence in situ
      hybridization analysis showing the cytogenetic lesion +8 or 7q- in
      differentiating cells. Hematologic improvement, according to established criteria
      for myelodysplastic syndromes, was observed in two cases. Stable disease and
      disease progression were observed in five and one cases, respectively. In
      conclusion, VPA-ATRA treatment is well tolerated and induces phenotypic changes
      of AML blasts through chromatin remodeling. Further studies are needed to
      evaluate whether VPA-ATRA treatment by reprogramming differentiation of the
      leukemic clone might improve the response to chemotherapy in leukemia patients.

PMID- 16951209
TI  - The extent and severity of vascular leakage as evidence of tumor aggressiveness
      in high-grade gliomas.
AB  - Magnetic resonance imaging reveals heterogeneous regions within high-grade
      gliomas, such as a contrast-enhanced rim, a necrotic core, and non-contrast
      enhanced abnormalities. It is unclear which of these regions best describes tumor
      aggressiveness. We hypothesized that the vascular leakage volume, reflecting
      disorganized angiogenesis typical of glioblastoma, would be a strong predictor of
      clinical outcome. The FLAIR tumor volume, post-gadolinium T1 tumor volume, tumor
      vascular leakage volume determined by dynamic contrast-enhanced imaging, and
      volume of the contrast-enhanced rim seen on post-gadolinium T1-weighted images
      were defined for 20 patients about to undergo treatment for newly diagnosed high
      grade gliomas. The potential for imaging characteristics to improve prediction of
      survival and time to progression over clinical variables was tested by using Cox
      regression analysis. Single-variable Cox regression analysis of each of the four
      tumor subvolumes revealed that the vascular leakage volume was the only
      significant predictor of survival. When the joint effect of clinical variables
      and the vascular leakage volume were tested for prediction of survival, only the
      age and the vascular leakage volume were selected as significant predictors.
      However, when time to progression was tested as a dependent variable, both the
      vascular leakage volume and the vascular permeability were selected as
      copredictors, along with surgical status. Our findings suggest that for patients
      with high-grade glioma, time to progression after radiation therapy is influenced
      by both underlying biological aggressiveness (vascularity) and volume of
      aggressive tumor. In contrast, survival depends chiefly on the volume of
      aggressive tumor at the time of presentation.

PMID- 16951210
TI  - Telomere maintenance mechanisms in liposarcomas: association with histologic
      subtypes and disease progression.
AB  - Human cancer cells maintain telomeres by telomerase activity (TA) or by
      alternative lengthening of telomeres (ALT). We proposed to define the prevalence
      of the two telomere maintenance mechanisms (TMM), to assess their association
      with histology, and to compare their prognostic relevance in a series of 93
      patients with liposarcoma. ALT was detected by assaying ALT-associated
      promyelocytic leukemia nuclear bodies and TA was assayed using the telomeric
      repeat amplification protocol. ALT or TA was found in 25.9% or 26.6% of 139
      tested liposarcoma lesions, respectively. Three lesions were ALT+/TA+ whereas
      approximately 50% of lesions did not show any known TMM. TMM phenotype was
      consistent during disease progression. ALT was prevalent in dedifferentiated and
      in grade 3 liposarcomas whereas TA prevailed in most round-cell myxoid and in
      grade 2 liposarcomas. ALT and TA incidence was similar in primary and recurrent
      lesions whereas metastases were more frequently TA+ than ALT+ (59% versus 18%; P
      = 0.04). TMM presence negatively affected patient prognosis (P = 0.001):
      increased mortality was associated with positivity for TA (P = 0.038) or ALT (P <
      0.0001) compared with TMM absence. ALT proved to be a stronger prognostic
      discriminant of increased mortality than TA even when adjusted for tumor
      location, grade, and histology (hazard ratio for cause-specific death, 3.58
      versus 1.15). Our results indicate that ALT can support fully malignant
      liposarcomas and is associated with unfavorable disease outcome.

PMID- 16951211
TI  - Aurora sheds light on head and neck squamous cell carcinoma.

PMID- 16951212
TI  - Prognostic biomarkers in head and neck cancer.

PMID- 16951213
TI  - Hypoxia-inducible factor-1 and p53: friends, acquaintances, or strangers?

PMID- 16951214
TI  - The science of selective estrogen receptor modulators: concept to clinical
      practice.

PMID- 16951215
TI  - Molecular screening testing for colorectal cancer.

PMID- 16951216
TI  - Vascular endothelial growth factor signaling pathways: therapeutic perspective.
AB  - The establishment of a vascular supply is one of the earliest and most important
      events occurring during embryonic development. Growth and maturation of a
      functional vascular network are complex and still incompletely understood
      processes involving orchestrated activation of vascular progenitors in the early
      stages of embryonic development followed by vasculogenesis and angiogenesis.
      These processes require a tightly regulated activation of several growth factors
      and their receptors. The role of vascular endothelial growth factors (VEGF) and
      their receptors has been studied extensively due to their prominent role during
      blood vessel formation. Mice deficient in various VEGF ligands or receptors show
      serious defects in vascular formation and maturation. Moreover, members of the
      VEGF family are involved in other significant biological processes, including
      lymphangiogenesis, vascular permeability, and hematopoiesis. Importantly, VEGF is
      released by tumor cells and induces tumor neovascularization. It is now well
      established that the VEGF axis represents an important target for antitumor
      therapy. Aberrant VEGF signaling is also a feature of several other pathologic
      conditions, such as age-related macular degeneration and rheumatoid arthritis.

PMID- 16951217
TI  - Unique tumor antigens: evidence for immune control of genome integrity and
      immunogenic targets for T cell-mediated patient-specific immunotherapy.
AB  - The molecular identification and characterization of antigenic epitopes
      recognized by T cells on human cancers has rapidly evolved since the cloning in
      1991 of MAGEA1, the first gene reported to encode a CTL-defined human tumor
      antigen. In the expanding field of human tumor immunology, unique tumor antigens
      constitute a growing class of T cell-defined epitopes that exhibit strong
      immunogenicity. Some of these antigens, which often derive from mutation of genes
      that have relevant biological functions, are less susceptible to immunoselection
      and may be retained even in advanced tumors. Immunogenicity and constitutive
      expression of the unique tumor antigens provide a strong rationale for the design
      of novel, patient-tailored therapies that target such determinants. Here we
      discuss the immunologic relevance of unique tumor antigens in the light of the
      prospects for exploiting such epitopes as targets for patient-specific immune
      intervention strategies.

PMID- 16951218
TI  - Validity of messenger RNA expression analyses of human saliva.
AB  - PURPOSE: The origins of expression microarray and reverse transcription-PCR (RT
      PCR) signals in human saliva were evaluated. EXPERIMENTAL DESIGN: The "RNA"
      extracts from human saliva samples were treated with vehicle, DNase, or RNase.
      Two-step amplification and hybridization to Affymetrix 133A cDNA microarrays were
      then done. Confirmatory RT-PCR experiments used conventionally designed PCR
      primer pairs for the reference housekeeper transcripts encoding 36B4, beta-actin,
      and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA sequences, which are
      known to be homologous to genomic DNA pseudogene sequences. Negative controls
      included the omission of reverse transcriptase ("no-RT") to detect any DNA
      derived signal. Finally, an RNA-specific RT-PCR strategy eliminated confounding
      signals from contaminating genomic DNA. RESULTS: Microarray experiments revealed
      that untreated, DNase-treated, and RNase-treated "RNA" extracts from saliva all
      yielded negligible overall signals. Specific microarray signals for 36B4, beta
      actin, and GAPDH were low, and were unaffected by RNase. Real-time quantitative
      RT-PCR reactions using conventional, non-RNA-specific primers on saliva samples
      yielded PCR products for 36B4, beta-actin, and GAPDH; DNase-treated saliva
      samples did not yield a PCR product, and the "no-RT" and "+RT" conditions yielded
      similar amounts of PCR product. The RNA-specific RT-PCR strategy, across all
      conditions, yielded no PCR product from saliva. CONCLUSIONS: The combination of
      (a) a minimal microarray signal, which was unaffected by RNase treatment, (b) the
      presence of a conventional RT-PCR housekeeper product in both RNase-treated and
      no-RT saliva samples, (c) the absence of a conventional RT-PCR housekeeper
      product in DNase-treated conditions, and (d) the absence of a RNA-specific RT-PCR
      product shows that any microarray or RT-PCR signal in the saliva must arise from
      genomic DNA, not RNA. Thus, saliva extracts do not support mRNA expression
      studies.

PMID- 16951219
TI  - Promoter hypermethylation profile of kidney cancer with new proapoptotic p53
      target genes and clinical implications.
AB  - PURPOSE: Risk stratification of renal cell carcinoma is based on the
      histopathologic classification. Promoter hypermethylation as a mechanism of gene
      inactivation in renal cell carcinoma has been shown for only a small number of
      genes. We examined the usefulness of quantitative methylation analysis with a new
      set of p53 target genes for determining the clinical outcome and aggressiveness
      of the tumor disease. EXPERIMENTAL DESIGN: The genes selected were APAF-1,
      CASPASE-8, DAPK-1, IGFBP-3, and PML. The tissue samples analyzed were taken from
      tumor specimens obtained from 90 consecutive patients with clear cell renal
      carcinoma and from 20 normal kidney specimens. Quantitative methylation analysis
      of CpG sites in the promoter region was done by methylation-specific real-time
      PCR and the normalized index of methylation (NIM) was determined for each sample.
      RESULTS: Hypermethylation of the promoter region was common for APAF-1 (97%) and
      DAPK-1 (41%) but not for IGFBP-3 (3%), PML (3%), or CASP-8 (0%). The tumor
      patients had a median follow-up of 55 months. A correlation was found between the
      methylation level of APAF-1 and tumor size and nodal status, but not for tumor
      stage, grade, and age of patient. Kaplan-Meier analysis was able to identify
      patients with a higher risk of recurrence and tumor-related death by using APAF-1
      (>or=56% NIM) and DAPK-1 (>or=10% NIM) methylation levels. In multivariate
      analysis, APAF-1 and DAPK-1 methylation levels were independent prognostic
      markers for metastatic disease and death from renal cell carcinoma. CONCLUSIONS:
      Our findings indicate that promoter hypermethylation of APAF-1 and DAPK-1 is a
      marker of aggressive renal cell carcinoma and provides independent prognostic
      information on disease outcome.

PMID- 16951220
TI  - Molecular heterogeneity of inflammatory breast cancer: a hyperproliferative
      phenotype.
AB  - PURPOSE: Inflammatory breast cancer (IBC) is associated with very poor prognosis.
      The aims of this study are (a) to prospectively identify differential gene
      expression patterns associated with IBC and (b) to confirm these pathways using
      tissue arrays. EXPERIMENTAL DESIGN: For gene expression analysis, IBC (n=14) was
      clinically defined as rapid-onset cancer associated with erythema and skin
      changes, whereas non-IBC patients (n=20) had stage III breast cancers, and cDNA
      analysis was carried out using the Affymetrix (Santa Clara, CA) HG-U133A
      microarrays. Tissue arrays were constructed from paraffin-embedded material, and
      the molecular phenotype of 75 IBC was compared with results from>2,000 non-IBC.
      RESULTS: Gene expression analyses indicated that IBC has higher expression of
      genes associated with increased metabolic rate, lipid signaling, and cell
      turnover relative to non-IBC tumors. Consistent with the expression analysis, IBC
      had statistically higher Ki-67 (93% versus 11%; P<0.001). BAX expression,
      reflecting increased apoptosis and cell turnover, was significantly uniformly
      higher in almost all IBC (98% versus 66%; P<0.05), whereas the expression of Bcl
      2 was not significantly different. IBC tumors were more likely to be steroid
      hormone receptor negative (estrogen receptor, 49% versus 30%; P=0.002;
      progesterone receptor, 68% versus 42%; P=0.001). The expression of tyrosine
      kinases was not significantly different. E-cadherin was found to be expressed in
      87% of IBC, whereas the expression p53 was not significantly different.
      CONCLUSION: This study is one of the largest molecular analyses of IBC. Both IBC
      and non-IBC are genetically heterogeneous with consistent differences in the
      molecular phenotype of IBC.

PMID- 16951221
TI  - Signal transducers and activators of transcription 3 pathway activation in drug
      resistant ovarian cancer.
AB  - PURPOSE: One of the major obstacles in the treatment of ovarian cancer is the
      development of multidrug resistance. Recent evidence shows that high-grade
      ovarian cancer often shows activation of the signal transducers and activators of
      transcription 3 (Stat3) pathway with subsequent transcription of genes that
      support tumor growth and survival. Less studied is the role of the Stat3 pathway
      in acquired drug resistance. There is no information on Stat3 expression in
      chemotherapy naive ovarian cancer as compared with tumors collected later in the
      natural history of the disease. To further clarify the significance of Stat3
      activation in ovarian cancer, here we investigated the Stat3 expression and
      activation in ovarian cancer and ovarian cancer multidrug resistance cell lines.
      EXPERIMENTAL DESIGN: Western blotting, electrophoretic mobility shift assay,
      luciferase assays, ELISA assay, and real-time reverse transcription-PCR
      determined interleukin-6 and Stat3 pathway expression and activation in cell
      lines. Stat3 expression in ovarian cancer tissue microarray was evaluated by
      immunohistochemistry. RESULTS: Activated (phosphorylated) Stat3 is overexpressed
      in most paclitaxel-resistant ovarian cancer cells. Inhibition of Stat3 activation
      results in significant decreases in paclitaxel resistance and enhanced apoptosis.
      Drug-resistant recurrent tumors have significantly greater phosphorylated Stat3
      (pStat3) expression as compared with matched primary tumors. Tumors with
      associated inflammatory cell infiltrates also have a higher proportion of cells
      staining intensely for nuclear phosphorylated Stat3 as compared with tumors
      without inflammatory infiltrates, consistent with paracrine activation of the
      Stat3 pathway by immune-mediated cytokines. CONCLUSIONS: These data support the
      hypothesis that interruption of Stat3 signaling could reverse resistance to
      paclitaxel and perhaps other chemotherapy agents in human cancer.

PMID- 16951222
TI  - Mutant epidermal growth factor receptor (EGFRvIII) contributes to head and neck
      cancer growth and resistance to EGFR targeting.
AB  - PURPOSE: Epidermal growth factor receptor (EGFR) is overexpressed in head and
      neck squamous cell carcinoma (HNSCC) where expression levels correlate with
      decreased survival. Therapies that block EGFR have shown limited efficacy in
      clinical trials and primarily when combined with standard therapy. The most
      common form of mutant EGFR (EGFRvIII) has been described in several cancers,
      chiefly glioblastoma. The present study was undertaken to determine the incidence
      of EGFRvIII expression in HNSCC and the biological consequences of EGFRvIII on
      tumor growth in response to EGFR targeting. EXPERIMENTAL DESIGN: Thirty-three
      HNSCC tumors were evaluated by immunostaining and reverse transcription-PCR for
      EGFRvIII expression. A representative HNSCC cell line was stably transfected with
      an EGFRvIII expression construct. EGFRvIII-expressing cells and vector
      transfected controls were compared for growth rates in vitro and in vivo as well
      as chemotherapy-induced apoptosis and the consequences of EGFR inhibition using
      the chimeric monoclonal antibody C225/cetuximab/Erbitux. RESULTS: EGFRvIII
      expression was detected in 42% of HNSCC tumors where EGFRvIII was always found in
      conjunction with wild-type EGFR. HNSCC cells expressing EGFRvIII showed increased
      proliferation in vitro and increased tumor volumes in vivo compared with vector
      transfected controls. Furthermore, EGFRvIII-transfected HNSCC cells showed
      decreased apoptosis in response to cisplatin and decreased growth inhibition
      following treatment with C225 compared with vector-transfected control cells.
      CONCLUSIONS: EGFRvIII is expressed in HNSCC where it contributes to enhanced
      growth and resistance to targeting wild-type EGFR. The antitumor efficacy of EGFR
      targeting strategies may be enhanced by the addition of EGFRvIII-specific
      blockade.

PMID- 16951223
TI  - Aberrant nuclear accumulation of glycogen synthase kinase-3beta in human
      pancreatic cancer: association with kinase activity and tumor dedifferentiation.
AB  - PURPOSE: We have shown recently that glycogen synthase kinase-3 (GSK-3) beta
      regulates nuclear factor-kappaB (NF-kappaB)-mediated pancreatic cancer cell
      survival and proliferation in vitro. Our objective was to determine the
      localization of GSK-3beta in pancreatic cancer cells and assess the antitumor
      effect of GSK-3 inhibition in vivo to improve our understanding of the mechanism
      by which GSK-3beta affects NF-kappaB activity in pancreatic cancer. EXPERIMENTAL
      DESIGN: Immunohistochemistry and cytosolic/nuclear fractionation were done to
      determine the localization of GSK-3beta in human pancreatic tumors. We studied
      the effect of GSK-3 inhibition on tumor growth, cancer cell proliferation, and
      survival in established CAPAN2 tumor xenografts using a tumor regrowth delay
      assay, Western blotting, bromodeoxyuridine incorporation, and terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling. RESULTS: We found
      nuclear accumulation of GSK-3beta in pancreatic cancer cell lines and in 62 of
      122 (51%) human pancreatic adenocarcinomas. GSK-3beta nuclear accumulation is
      significantly correlated with human pancreatic cancer dedifferentiation. We have
      found that active GSK-3beta can accumulate in the nucleus of pancreatic cancer
      cells and that inhibition of GSK-3 kinase activity represses its nuclear
      accumulation via proteasomal degradation within the nucleus. Lastly, we have
      found that inhibition of GSK-3 arrests pancreatic tumor growth in vivo and
      decreases NF-kappaB-mediated pancreatic cancer cell survival and proliferation in
      established tumor xenografts. CONCLUSIONS: Our results show the antitumor effect
      of GSK-3 inhibition in vivo, identify GSK-3beta nuclear accumulation as a
      hallmark of poorly differentiated pancreatic adenocarcinoma, and provide new
      insight into the mechanism by which GSK-3beta regulates NF-kappaB activity in
      pancreatic cancer.

PMID- 16951224
TI  - Rac activation is associated with hepatocellular carcinoma metastasis by up
      regulation of vascular endothelial growth factor expression.
AB  - PURPOSE: Hepatocellular carcinoma (HCC) is associated with a propensity for
      vascular invasion and metastasis, which contribute to poor prognosis.
      Angiogenesis is a crucial process contributing to tumor growth and metastasis.
      Recently, Rac has been suggested to play a role in angiogenesis. However, the
      actual role of Rac in HCC angiogenesis remains unclear. Given that vascular
      endothelial growth factor (VEGF) is an important angiogenic factor in HCC, the
      purpose of this study was to evaluate the possible correlation between Rac
      activation and VEGF expression in HCC tumor samples, as well as the mechanism
      involved in Rac-induced HCC angiogenesis. EXPERIMENTAL DESIGN: We evaluated Rac
      and VEGF expression in the HCC tissue microarray of paired primary and metastatic
      HCC samples using immunohistochemical staining. The role of Rac-induced HCC
      angiogenesis was also evaluated in vitro in HCC cell lines. RESULTS: We first
      showed that activation of Rac was correlated with HCC metastasis (P<0.001), and
      its expression was significantly correlated with VEGF expression by tissue
      microarray. Ectopic Rac-dominant active transfection in Hep3B cells increased
      VEGF secretion, which induced the morphologic change and proliferation of human
      umbilical vein endothelial cells, resulting in the promotion of angiogenesis. Rac
      induced the transcriptional activation of VEGF by direct interaction with hypoxia
      inducible factor-1alpha (HIF-1alpha) expression. In hypoxic conditions, Rac
      promoted angiogenesis through an increase in HIF-1alpha stabilization.
      CONCLUSION: This study shows that Rac is a novel angiogenic factor for HCC
      through the enhancement of HIF-1alpha protein stability, which provides a
      possible therapeutic target in the development of inhibitors of angiogenesis.

PMID- 16951225
TI  - Fatty acid binding protein 6 is overexpressed in colorectal cancer.
AB  - PURPOSE: Fatty acid binding protein 6 (FABP6) is a cancer-related protein that
      acts as an intracellular transporter of bile acid in the ileal epithelium.
      Because bile acids are implicated in the carcinogenesis of colorectal cancer, we
      evaluated FABP6 expression in colorectal cancer. EXPERIMENTAL DESIGN: The
      expression of FABP6 mRNA was evaluated in 78 paired samples of cancer/normal
      tissue representing colorectal cancer cases, plus 16 adenomas, and 16 metastatic
      lymph nodes. An immunohistochemical study was conducted with paraffin sections.
      In vitro transfection was done to determine FABP6's biological roles. RESULTS:
      The expression of FABP6 mRNA was significantly higher in cancer (75 of 78, 96.2%)
      than in normal tissue (P<0.001). The expression of mRNA was increased in cancer
      compared with adenoma, but was dramatically decreased in node metastases. Tumors
      with high FABP6 expression were smaller in size (P<0.01), more often in the left
      colon (P<0.05), and had shallower invasion into the bowel wall (P<0.05) compared
      with those with low expression. There was no significant difference between high-
      and low-expression tumors regarding clinicopathologic variables such as
      histologic type, lymph node, or liver metastasis, Dukes' classification, and
      prognosis. Immunohistochemical study revealed that FABP6 expression was primarily
      observed in cancer cells. In vitro transfection revealed that transfectants
      showed weaker invasiveness (P<0.05), more dominant proliferation (P<0.001), and
      less apoptosis than mock cells. CONCLUSIONS: The expression of FABP6 was higher
      in primary colorectal cancers and adenomas than in normal epithelium, but was
      dramatically decreased in lymph node metastases, suggesting that FABP6 may play
      an important role in early carcinogenesis.

PMID- 16951226
TI  - The biological role of the low-affinity p75 neurotrophin receptor in esophageal
      squamous cell carcinoma.
AB  - In this study, we investigated the clinicopathologic significance of the low
      affinity p75 neurotrophin receptor (p75NTR; which is expressed in the
      stem/progenitor cell fraction of normal esophageal epithelial cells) in 187
      resected esophageal squamous cell carcinoma (ESCC) specimens and found that
      approximately 50% of ESCC expressed p75NTR. Our investigation using ESCC cell
      lines showed that p75NTR was intensely expressed in the cells with high colony
      forming capacity but they were sensitive to cell death on inhibition of p75NTR
      expression with transient transfection of small interfering RNA (siRNA). These
      findings suggest that p75NTR is necessary for survival and maintenance of ESCC
      tumors, providing us with a potential target for novel therapies. PURPOSE: p75NTR
      is expressed in a stem/progenitor cell fraction of human normal esophageal
      epithelial cells. In this study, we investigated the expression and biological
      role of p75NTR in ESCC. EXPERIMENTAL DESIGN: The expression of p75NTR in 187
      resected ESCC specimens was immunohistochemically investigated. The expression of
      p75NTR in 30 ESCC cell lines (KYSEs) was assessed by reverse transcription-PCR,
      immunocytochemistry, and flow cytometry. The p75NTR-bright and p75NTR
      dim/negative cells were isolated from KYSE150 by magnetic beads and colony
      formation was investigated. The role of p75NTR in KYSEs was assessed by transient
      transfection of siRNA. RESULTS: p75NTR was expressed in 92 of 187 (49.2%) tumors.
      In well-differentiated tumors, positive staining was apparent in the first one to
      two layers from infiltrative margin of the tumors where most of the cells were
      actively proliferating. In moderately differentiated tumors, p75NTR was expressed
      in wider range from the margin of the tumors whereas p75NTR was diffusely
      distributed in poorly differentiated tumors. p75NTR was expressed in all examined
      KYSEs and the mean proportion of the p75NTR-bright fraction was 30.1%. The size
      of p75NTR-positive colonies was larger than that of p75NTR-negative colonies
      derived from KYSE150 (P<0.0001). The purified p75NTR-bright cells formed p75NTR
      positive large colonies more frequently than the p75NTR-dim/negative cells
      (P<0.0001). Down-regulation of p75NTR expression by siRNA resulted in marked
      growth inhibition with induction of apoptosis. CONCLUSIONS: Our findings suggest
      that p75NTR is necessary for survival and maintenance of ESCC tumors, providing
      us with a potential target for novel therapies.

PMID- 16951227
TI  - DNA repair pathway profiling and microsatellite instability in colorectal cancer.
AB  - BACKGROUND: The ability to maintain DNA integrity is a critical cellular
      function. DNA repair is conducted by distinct pathways of genes, many of which
      are thought to be altered in colorectal cancer. However, there has been little
      characterization of these pathways in colorectal cancer. METHOD: By using the
      TaqMan real-time quantitative PCR, RNA expression profiling of 20 DNA repair
      pathway genes was done in matched tumor and normal tissues from 52 patients with
      Dukes' C colorectal cancer. RESULTS: The relative mRNA expression level across
      the 20 DNA repair pathway genes varied considerably, and the individual
      variability was also quite large, with an 85.4 median fold change in the tumor
      tissue genes and a 127.2 median fold change in the normal tissue genes. Tumor
      normal differential expression was found in 13 of 20 DNA repair pathway genes
      (only XPA had a lower RNA level in the tumor samples; the other 12 genes had
      significantly higher tumor levels, all P<0.01). Coordinated expression of ERCC6,
      HMG1, MSH2, and POLB (RS>or=0.60) was observed in the tumor tissues (all
      P<0.001). Apoptosis index was not correlated with expression of the 20 DNA repair
      pathway genes. MLH1 and XRCC1 RNA expression was correlated with microsatellite
      instability status (P=0.045 and 0.020, respectively). An inverse correlation was
      found between tumor MLH1 RNA expression and MLH1 DNA methylation (P=0.003).
      CONCLUSION: Our study provides an initial characterization of the DNA repair
      pathways for understanding the cellular DNA damage/repair system in human
      colorectal cancer.

PMID- 16951228
TI  - Overexpression of hypoxia-inducible factor 1alpha and p53 is a marker for an
      unfavorable prognosis in gastric cancer.
AB  - PURPOSE: To investigate the effects of the expression of hypoxia-inducible factor
      1alpha (HIF-1alpha) and p53 on the prognosis of human gastric cancer, the
      clinicopathologic characteristics of the tumors and the clinical outcome were
      analyzed. EXPERIMENTAL DESIGN: The expressions of HIF-1alpha and p53 proteins
      were studied by immunohistochemistry in 216 specimens of primary gastric cancer.
      RESULTS: HIF-1alpha(+)/p53(+) tumors more frequently showed an undifferentiated
      type, an infiltrative growth appearance, and an invasive lymphatic involvement
      compared with HIF-1alpha(-)/p53(-) tumors. HIF-1alpha(+)/p53(+) tumors also had
      more lymph node metastasis compared with HIF-1alpha(-)/p53(-) tumors. When
      stratified for HIF-1alpha and p53 positivity, the patients who were p53-negative
      and HIF-1alpha-negative had the most favorable prognosis, whereas patients who
      were p53-positive and HIF-1alpha-positive had the worst prognosis (P=0.0018).
      Using a multivariate Cox regression analysis, the depth of invasion, lymph node
      metastasis, and HIF-1alpha positivity were all found to be independent prognostic
      factors in patients with gastric cancer. CONCLUSION: Thus, HIF-1alpha is
      considered to be a useful independent prognostic factor in gastric cancer, and
      the combination of a HIF-1alpha protein overexpression with nonfunctional p53
      tends to indicate a dismal prognosis.

PMID- 16951229
TI  - Differential expression of neuronal genes defines subtypes of disseminated
      neuroblastoma with favorable and unfavorable outcome.
AB  - PURPOSE: Identification of molecular characteristics of spontaneously regressing
      stage IVS and progressing stage IV neuroblastoma to improve discrimination of
      patients with metastatic disease following favorable and unfavorable clinical
      courses. EXPERIMENTAL DESIGN: Serial analysis of gene expression profiles were
      generated from five stage IVS and three stage IV neuroblastoma. Differential
      expression of candidate genes was evaluated by real-time quantitative reverse
      transcription-PCR in 76 pretreatment tumor samples (stage IVS n=27 and stage IV
      n=49). Gene expression-based outcome prediction was determined by Prediction
      Analysis for Microarrays using 38 tumors as a training set and 38 tumors as a
      test set. RESULTS: Comparison of serial analysis of gene expression profiles from
      stage IV and IVS neuroblastoma revealed approximately 500 differentially
      expressed transcripts. Genes related to neuronal differentiation were observed
      more frequently in stage IVS tumors as determined by associating transcripts to
      Gene Ontology annotations. Forty-one candidate genes were evaluated by
      quantitative reverse transcription-PCR and 18 were confirmed to be differentially
      expressed (P<or=0.001). Classification of patients according to expression
      patterns of these 18 genes using Prediction Analysis for Microarrays
      discriminated two subgroups with significantly differing event-free survival
      (96+/-6% versus 40+/-8% at 3 years; P<0.0001) and overall survival (100% versus
      72+/-7% at 3 years; P=0.0003). This classifier was the only independent covariate
      marker in a multivariate analysis considering the variables stage, age, MYCN
      amplification, and gene signature. CONCLUSIONS: Spontaneously regressing and
      progressing metastatic neuroblastoma differ by specific gene expression patterns,
      indicating distinct levels of neuronal differentiation and allowing for an
      improved risk estimation of children with disseminated disease.

PMID- 16951230
TI  - A molecular diagnostic test for distinguishing lung adenocarcinoma from malignant
      mesothelioma using cells collected from pleural effusions.
AB  - PURPOSE: Patients with malignant mesothelioma or adenocarcinoma of the lung often
      present with respiratory complications associated with a malignant pleural
      effusion. Distinguishing between these malignancies is frequently problematic, as
      many of the clinical, cytologic, and histologic features of the diseases overlap.
      Following cytologic analysis of pleural effusions, subsequent confirmatory tissue
      biopsies involve increased patient morbidity and expense. We have therefore
      designed a gene expression-based test to classify the primary tumor causing a
      malignant pleural effusion, using cells collected from the effusion itself.
      EXPERIMENTAL DESIGN: We have used microarray data for 190 lung adenocarcinomas
      and 33 malignant mesotheliomas to identify genes differentially expressed between
      the two diseases. Genes expressed in normal mesothelial cells were removed,
      allowing the development of a PCR-based test to measure the expression of genes
      that discriminate between mesothelioma and lung adenocarcinoma from cytology
      specimens. RESULTS: Applying an real-time PCR-based assay involving 17 genes to
      13 independent samples from biopsy-proven malignant mesothelioma and lung
      adenocarcinomas resulted in the correct identification of all samples.
      CONCLUSIONS: We have developed a test that is able to distinguish between lung
      adenocarcinoma and mesothelioma in cells collected from pleural effusions.

PMID- 16951231
TI  - Aurora kinase A messenger RNA overexpression is correlated with tumor progression
      and shortened survival in head and neck squamous cell carcinoma.
AB  - PURPOSE: Aurora kinase A (AURKA/STK15/BTAK) encodes a serine/threonine kinase
      associated with chromosomal distribution and its up-regulation induces
      chromosomal instability, thereby leading to aneuploidy and cell transformation in
      several types of cancer. In this study, we investigated the role of AURKA in head
      and neck squamous cell carcinoma (HNSCC). EXPERIMENTAL DESIGN: The mRNA
      expression levels of AURKA were compared in tumor tissues of 66 HNSCC patients
      with those in corresponding normal squamous epithelium by real-time quantitative
      reverse transcriptase-PCR. In addition, the association between AURKA mRNA and
      protein expression, centrosome abnormalities, and aneuploidy was studied in a
      subset of cases (n=34). All molecular variables were correlated to
      histomorphologic findings and clinical follow-up data of the patients. RESULTS:
      AURKA mRNA up-regulation was significantly associated with tumor stage and the
      occurrence of regional lymph node, as well as distant metastasis (P<0.0001 for
      all). Similarly, a correlation was found for protein expression and the
      occurrence of regional lymph node (P=0.0183) and distant metastasis (P=0.03). The
      mRNA was positively associated with protein expression (P=0.003) and centrosome
      abnormalities (P=0.03). Cox regression analysis revealed that AURKA mRNA up
      regulation correlated with disease-free survival of the patients (P=0.03) as well
      as shorter overall survival (P<0.001). CONCLUSIONS: We conclude that the up
      regulation of AURKA mRNA may play a critical role in the tumor progression of
      HNSCC and provides useful information as a prognostic factor for HNSCC patients.

PMID- 16951232
TI  - Selective profiling of proteins in lung cancer cells from fine-needle aspirates
      by matrix-assisted laser desorption ionization time-of-flight mass spectrometry.
AB  - PURPOSE: Matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) has been used to analyze tumor sections and can
      determine tumor type, nodal involvement, and survival, and shows promise in
      predicting therapeutic response. Our purpose was to develop a method compatible
      with MALDI-TOF MS that allows selective analysis of cancer cells in mixed
      clinical samples such as fine-needle aspirates. EXPERIMENTAL DESIGN: Lung cancer
      cell lines were cytocentrifuged onto metal-coated, transparent glass slides and
      used for optimization of fixation, staining, and RBC lysis protocols. Fine-needle
      aspirates from human tumors and mouse model tumors were used to provide fresh
      tissue samples for determining the feasibility of this method. RESULTS: The MALDI
      TOF MS compatible fixation and staining techniques provided high-resolution
      cellular morphology, which allowed identification and selective spotting of tumor
      cells. The RBC lysis step efficiently removed contaminating RBC yielding spectra
      nearly free from hemoglobin peaks. Protein profiles of fine-needle aspirates were
      found highly reproducible and similar to the profiles of the tissue from which
      they were obtained. Using this method, we were able to differentiate between
      xenograft tumors derived from two different human cell lines, A549 and H460.
      CONCLUSION: This procedure results in the production of high-quality, cancer cell
      specific protein profiles. This highly reproducible technique could be applied to
      many other types of mixed clinical samples and has the potential to be very
      useful in the clinical diagnosis, classification, and, potentially, the
      individualized treatment of cancer patients.

PMID- 16951233
TI  - Microsatellite DNA alterations of gastrointestinal stromal tumors are predictive
      for outcome.
AB  - PURPOSE: In gastrointestinal stromal tumors (GIST), loss of heterozygosity (LOH)
      on chromosome 22 and its presumptive biological function has been described. The
      prognostic value of these and other DNA regions for patient survival remains
      unclear. EXPERIMENTAL DESIGN: Sixty patients who underwent surgery at our
      institution between 1992 and 2003 for GIST were histopathologically reclassified
      by immunohistochemistry and the GIST consensus group criteria 2001. Twenty-one
      microsatellite loci on chromosomes 3, 9, 13, 17, 18, and 22 were screened for
      alterations in tumor and healthy DNA. Survival was calculated by Kaplan-Meier
      plots. RESULTS: Eleven (18.3%) of 60 patients showed metastases at presentation.
      Thirteen (21.7%) of 60 were high-risk GISTs. LOH was found in all tumors. Twenty
      eight (46.7%) of 60 showed more than two LOH in 21 microsatellite marker sites.
      The frequency of single marker LOH varied from 1.7% to 28.3% among tumors.
      Frequent LOH was found on chromosomes 22 and 17. The correlation of LOH
      positivity and the consensus scoring was significant (P=0.005, chi2 test). After
      a median observation time of 33.3 months (95% confidence interval, 23.9-42.6),
      overall survival was best for patients with tumors of very low, low, and
      intermediate risks with only 6 of 36 death events, whereas 14 of 24 high-risk and
      metastasized patients had died (P<0.001, log-rank test). Likewise, LOH
      significantly predicted survival (P=0.013) and the effect was particularly
      detrimental for LOH on chromosome 17 (P<0.001). CONCLUSIONS: LOH is a useful
      phenomenon for the prognosis of GIST. Rather than chromosome 22 markers,
      chromosome 17 markers independently predict survival.

PMID- 16951234
TI  - Identification of cripto-1 as a novel serologic marker for breast and colon
      cancer.
AB  - PURPOSE: Human Cripto-1 (CR-1), a cell membrane glycosylphosphatidylinositol
      anchored glycoprotein that can also be cleaved from the membrane, is expressed at
      high levels in several different types of human tumors. We evaluated whether CR-1
      is present in the plasma of patients with breast and colon cancer, and if it can
      represent a new biomarker for these malignancies. EXPERIMENTAL DESIGN: We
      determined CR-1 plasma levels using a sandwich-type ELISA in 21 healthy
      volunteers, 54 patients with breast cancer, 33 patients with colon carcinoma, and
      21 patients with benign breast lesions. Immunohistochemical analysis was also
      used to assess CR-1 expression in cancerous tissues. RESULTS: Very low levels of
      CR-1 (mean+/-SD) were detected in the plasma of healthy volunteers (0.32+/-0.19
      ng/mL). A statistically significant increase in the levels of plasma CR-1 was
      found in patients with colon carcinoma (4.68+/-3.5 ng/mL) and in patients with
      breast carcinoma (2.97+/-1.48 ng/mL; P<0.001). Although moderate levels of plasma
      CR-1 were found in women with benign lesions of the breast (1.7+/-0.99 ng/mL),
      these levels were significantly lower than in patients with breast cancer
      (P<0.001). Finally, immunohistochemical analysis and real-time reverse
      transcription-PCR confirmed strong positivity for CR-1 in colon and/or breast
      tumor tissues. CONCLUSION: This study suggests that plasma CR-1 might represent a
      novel biomarker for the detection of breast and colon carcinomas.

PMID- 16951235
TI  - Phase I/II study of the mammalian target of rapamycin inhibitor everolimus
      (RAD001) in patients with relapsed or refractory hematologic malignancies.
AB  - PURPOSE: Everolimus (RAD001, Novartis), an oral derivative of rapamycin, inhibits
      the mammalian target of rapamycin (mTOR), which regulates many aspects of cell
      growth and division. A phase I/II study was done to determine safety and efficacy
      of everolimus in patients with relapsed or refractory hematologic malignancies.
      EXPERIMENTAL DESIGN: Two dose levels (5 and 10 mg orally once daily continuously)
      were evaluated in the phase I portion of this study to determine the maximum
      tolerated dose of everolimus to be used in the phase II study. RESULTS: Twenty
      seven patients (9 acute myelogenous leukemia, 5 myelodysplastic syndrome, 6 B
      chronic lymphocytic leukemia, 4 mantle cell lymphoma, 1 myelofibrosis, 1 natural
      killer cell/T-cell leukemia, and 1 T-cell prolymphocytic leukemia) received
      everolimus. No dose-limiting toxicities were observed. Grade 3 potentially drug
      related toxicities included hyperglycemia (22%), hypophosphatemia (7%), fatigue
      (7%), anorexia (4%), and diarrhea (4%). One patient developed a cutaneous
      leukocytoclastic vasculitis requiring a skin graft. One patient with refractory
      anemia with excess blasts achieved a major platelet response of over 3-month
      duration. A second patient with refractory anemia with excess blasts showed a
      minor platelet response of 25-day duration. Phosphorylation of downstream targets
      of mTOR, eukaryotic initiation factor 4E-binding protein 1, and/or, p70 S6
      kinase, was inhibited in six of nine patient samples, including those from the
      patient with a major platelet response. CONCLUSIONS: Everolimus is well tolerated
      at a daily dose of 10 mg daily and may have activity in patients with
      myelodysplastic syndrome. Studies of everolimus in combination with therapeutic
      agents directed against other components of the phosphatidylinositol 3
      kinase/Akt/mTOR pathway are warranted.

PMID- 16951236
TI  - The effect of enzyme-inducing antiseizure drugs on the pharmacokinetics and
      tolerability of procarbazine hydrochloride.
AB  - PURPOSE: Procarbazine hydrochloride (PCB) is one of the few anticancer drugs with
      activity against high-grade gliomas. This study was conducted to determine if the
      maximum tolerated dose and pharmacokinetics of PCB are affected by the concurrent
      use of enzyme-inducing antiseizure drugs (EIASD). EXPERIMENTAL DESIGN: Adults
      with recurrent high-grade glioma were divided into cohorts who were (+) and were
      not (-) taking EIASDs. PCB was given orally for 5 consecutive days each month.
      Six patients were evaluated at each dose level beginning with 200 mg/m2/d and
      escalated using the modified continual reassessment method. Toxicity and response
      were assessed. Pharmacokinetic studies were done with a new electrospray
      ionization mass spectrometry assay. RESULTS: Forty-nine patients were evaluated.
      The maximum tolerated dose was 393 mg/m2/d for the +EIASD group and the highest
      dose evaluated in -EIASD patients was 334 mg/m2/d. Myelosuppression was the
      primary dose-limiting toxicity. Significant hepatic dysfunction occurred in three
      patients in the +EIASD cohort. Four partial responses (8%) and no complete
      responses were observed. PCB exhibited linear pharmacokinetics with no
      significant differences between the two cohorts. A marked increase in peak PCB
      levels was noted on day 5 relative to day 1, which was not attributable to drug
      accumulation. CONCLUSIONS: This study suggests that (a) EIASD use does not
      significantly affect the pharmacokinetics of PCB; (b) changes in the peak plasma
      concentration of PCB, consistent with decreased apparent oral clearance due to
      autoinhibition of hepatic metabolism, occur with daily dosing; and (c) severe
      hepatic dysfunction may accompany this administration schedule.

PMID- 16951237
TI  - A phase I pharmacokinetic study of HMN-214, a novel oral stilbene derivative with
      polo-like kinase-1-interacting properties, in patients with advanced solid
      tumors.
AB  - PURPOSE: HMN-214 is an oral prodrug of HMN-176, a stilbene derivative that
      interferes with the subcellular spatial location of polo-like kinase-1, a
      serine/threonine kinase that regulates critical mitotic events. We conducted a
      dose escalation study of HMN-214 in patients with advanced cancer to assess the
      safety profile and pharmacokinetics of HMN-214 and to establish the maximum
      tolerated dose. EXPERIMENTAL DESIGN: Thirty-three patients were enrolled onto
      four dosing cohorts of HMN-214 from 3 to 9.9 mg/m2/d using a continuous 21-day
      dosing schedule every 28 days, with pharmacokinetic sampling during cycle 1.
      RESULTS: A severe myalgia/bone pain syndrome and hyperglycemia were dose-limiting
      toxicities at 9.9 mg/m2/d. A dose reduction and separate enrollment by
      pretreatment status (lightly versus heavily pretreated) was undertaken, with one
      dose-limiting toxicity (grade 3 bone pain) at 8 mg/m2/d. The maximum tolerated
      dose was defined as 8 mg/m2/d for both treatment cohorts. Dose-proportional
      increases were observed in AUC but not Cmax. There was no accumulation of HMN
      176, the metabolite of HMN-214, with repeated dosing. Seven of 29 patients had
      stable disease as best tumor response, including 6-month stable disease in a
      heavily pretreated breast cancer patient. A transient decline in carcinoembryonic
      antigen in a patient with colorectal cancer was noted. CONCLUSIONS: The maximum
      tolerated dose and recommended phase II dose of HMN-214 when administered on this
      schedule was 8 mg/m2/d regardless of pretreatment status. Further development of
      HMN-214 will focus on patient populations for which high expression of polo-like
      kinase-1 is seen (i.e., prostate and pancreatic cancer patients).

PMID- 16951238
TI  - High-Dose celecoxib and metronomic "low-dose" cyclophosphamide is an effective
      and safe therapy in patients with relapsed and refractory aggressive histology
      non-Hodgkin's lymphoma.
AB  - PURPOSE: Angiogenesis is increased in aggressive histology non-Hodgkin's lymphoma
      and may be a target with selective cyclooxygenase-2 inhibition and metronomic
      chemotherapy. EXPERIMENTAL DESIGN: We assessed response, toxicity, and biomarkers
      of angiogenesis to low-dose cyclophosphamide (50 mg p.o. o.d.) and high-dose
      celecoxib (400 mg p.o. b.i.d.) in adult patients with relapsed or refractory
      aggressive non-Hodgkin's lymphoma in a multicenter phase II prospective study.
      RESULTS: Thirty-two of 35 patients (median age, 62 years) are evaluable for
      response. Patients had primarily relapsed diffuse large B-cell lymphoma (63%)
      were heavily pretreated (median of three regimens) and high risk (79%
      international prognostic index, >or=2) and 34% were relapsed after autologous
      stem cell transplant. With a median follow-up of 8.4 months, the overall best
      response rate is 37% (2 complete clinical response/complete clinical response
      unconfirmed and 9 partial response), with 22% achieving stable disease. Median
      overall and progression-free survivals are 14.4 and 4.7 months, respectively. The
      median response duration was 8.2 months. The most common toxicity was skin rash
      (40%); myelosuppression and gastrointestinal side effects were uncommon. Three
      patients developed deep vein thromboses and two heavily pretreated patients
      developed treatment-related acute myelogenous leukemia or myelodysplasia after
      3.7 and 12 months of therapy. Circulating endothelial cells and their precursors
      declined and remained low in responders, whereas plasma vascular endothelial
      growth factor trended to decline in responding patients but increase in
      nonresponders. Trough celecoxib levels achieved targeted "antiangiogenic" levels.
      CONCLUSIONS: Low-dose cyclophosphamide and high-dose celecoxib is well tolerated
      and active in pretreated aggressive non-Hodgkin's lymphoma. Close surveillance
      for arterial and venous thrombotic events is recommended. The decline in
      circulating endothelial cells and their precursors suggests that this combination
      may be working by inhibiting angiogenesis but should be validated in a larger
      patient sample.

PMID- 16951239
TI  - Antitumor effects of a novel phenylbutyrate-based histone deacetylase inhibitor,
      (S)-HDAC-42, in prostate cancer.
AB  - PURPOSE: To assess the antitumor effects of a novel phenylbutyrate-derived
      histone deacetylase (HDAC) inhibitor, (S)-HDAC-42, vis-a-vis suberoylanilide
      hydroxamic acid (SAHA) in in vitro and in vivo models of human prostate cancer.
      EXPERIMENTAL DESIGN: The in vitro effects of (S)-HDAC-42 and SAHA were evaluated
      in PC-3, DU-145, or LNCaP human prostate cancer cell lines. Cell viability,
      apoptosis, and indicators of HDAC inhibition were assessed. Effects on Akt and
      members of the Bcl-2 and inhibitor of apoptosis protein families were determined
      by immunoblotting. Immunocompromised mice bearing established s.c. PC-3 xenograft
      tumors were treated orally with (S)-HDAC-42 (50 mg/kg q.o.d. or 25 mg/kg q.d.) or
      SAHA (50 mg/kg q.d.) for 28 days. In vivo end points included tumor volumes and
      intratumoral changes in histone acetylation, phospho-Akt status, and protein
      levels of Bcl-xL and survivin. RESULTS: (S)-HDAC-42 was more potent than SAHA in
      suppressing the viability of all cell lines evaluated with submicromolar IC50
      values. Relative to SAHA, (S)-HDAC-42 exhibited distinctly superior apoptogenic
      potency, and caused markedly greater decreases in phospho-Akt, Bcl-xL, and
      survivin in PC-3 cells. The growth of PC-3 tumor xenografts was suppressed by 52%
      and 67% after treatment with (S)-HDAC-42 at 25 and 50 mg/kg, respectively,
      whereas SAHA at 50 mg/kg suppressed growth by 31%. Intratumoral levels of phospho
      Akt and Bcl-xL were markedly reduced in (S)-HDAC-42-treated mice, in contrast to
      mice treated with SAHA. CONCLUSIONS: (S)-HDAC-42 is a potent orally bioavailable
      inhibitor of HDAC, as well as targets regulating multiple aspects of cancer cell
      survival, which might have clinical value in prostate cancer chemotherapy and
      warrants further investigation in this regard.

PMID- 16951240
TI  - Phase I and pharmacokinetic study of tasidotin hydrochloride (ILX651), a third
      generation dolastatin-15 analogue, administered weekly for 3 weeks every 28 days
      in patients with advanced solid tumors.
AB  - PURPOSE: To determine the safety, tolerability, and pharmacokinetics and to seek
      preliminary evidence of anticancer activity of tasidotin (ILX651), a novel
      dolastatin analogue, when administered as a 30-minute i.v. infusion weekly for 3
      weeks every 4 weeks. EXPERIMENTAL DESIGN: Thirty patients with advanced solid
      malignancies were treated with 82 courses at six dose levels ranging from 7.8 to
      62.2 mg/m2 weekly, initially according to an accelerated dose-escalation scheme,
      which evolved into a Fibonacci scheme as a relevant degree of toxicity was
      observed. Plasma and urine were sampled to characterize the pharmacokinetic
      behavior of tasidotin. RESULTS: A high incidence of neutropenia complicated by
      fever (one patient), or precluding treatment on day 15 (three patients), was the
      principal toxicity of tasidotin, at doses above 46.8 mg/m2. At all dose levels,
      nonhematologic toxicities were generally mild to moderate and manageable. Grade 3
      toxicities included diarrhea and vomiting (one patient each). Drug-induced
      neurosensory symptoms were mild and there was no evidence of cardiovascular
      toxicity, which has been previously associated with other dolastatins. Tasidotin
      pharmacokinetics were mildly nonlinear, whereas metabolite kinetics were linear.
      A patient with non-small cell lung carcinoma experienced a minor response, and a
      patient with hepatocellular carcinoma had stable disease lasting 11 months.
      CONCLUSIONS: The recommended dose for phase II studies of tasidotin administered
      on this schedule is 46.8 mg/m2. The mild myelosuppression and manageable
      nonhematologic toxicities at the recommended dose, the evidence of antitumor
      activity, and the unique mechanistic aspects of tasidotin warrant further disease
      directed evaluations on this and alternative schedules.

PMID- 16951241
TI  - Adenovirus-mediated calponin h1 gene therapy directed against peritoneal
      dissemination of ovarian cancer: bifunctional therapeutic effects on peritoneal
      cell layer and cancer cells.
AB  - PURPOSE: Calponin h1 (CNh1), one of the family of actin-binding proteins,
      stabilizes the filaments of actin and modulates various cellular biological
      phenotypes. Recent studies revealed the close correlation between the invasive
      tumor spread and the reduced expression of CNh1 and alpha-smooth muscle actin in
      the surrounding stromal cells. The purpose of this study is to evaluate the
      efficacy of i.p. CNh1 gene therapy against peritoneal dissemination of ovarian
      cancer. EXPERIMENTAL DESIGN: We used an adenoviral vector to induce the CNh1 gene
      into peritoneal cells and ovarian cancer cells as a means of enhancing or
      inducing the expression of alpha-smooth muscle actin as well as CNh1. The
      efficacy of gene transfer was examined by in vitro cell culture and in vivo
      animal experiments. RESULTS: The formation of longer and thicker actin fibers was
      observed in each transfected cell line, and the localization of these fibers
      coincided with that of externally transducted CNh1. With respect to changes in
      cell behavior, the CNh1-transfected peritoneal cells acquired an ability to
      resist ovarian cancer-induced shrinkage in cell shape; thus, cancer cell invasion
      through the monolayer of peritoneal cells was inhibited. In addition, CNh1
      transfected ovarian cancer cells showed suppressed anchorage-independent growth
      and invasiveness, the latter of which accompanied impaired cell motility. The
      concomitant CNh1 transfection into both peritoneal cells and ovarian cancer cells
      produced an additive inhibitory effect with respect to cancer cell invasion
      through the peritoneal cell monolayer. By in vivo experiments designed to treat
      nude mice that had been i.p. inoculated with ovarian cancer cells, we found that
      the i.p. injected CNh1 adenovirus successfully blocked cancer-induced morphologic
      changes in peritoneal cell surface and significantly prolonged the survival time
      of tumor-bearing mice. Moreover, CNh1 adenovirus could successfully enhance the
      therapeutic effect of an anticancer drug without increase in side effects.
      CONCLUSIONS: Thus, CNh1 gene therapy against peritoneal dissemination of ovarian
      cancer is bifunctionally effective (i.e., through inhibitory effects on the
      infected peritoneal cell layers that suppress cancer invasion and through direct
      antitumor effects against invasion and growth properties of cancer cells).

PMID- 16951242
TI  - Eliminating established tumor in nu/nu nude mice by a tumor necrosis factor-alpha
      related apoptosis-inducing ligand-armed oncolytic adenovirus.
AB  - PURPOSE: The tumor necrosis factor-alpha-related apoptosis-inducing ligand
      (TRAIL) and oncolytic viruses have recently been investigated extensively for
      cancer therapy. However, preclinical and clinical studies have revealed that
      their clinical application is hampered by either weak anticancer activity or
      systemic toxicity. We examined whether the weaknesses of the two strategies can
      be overcome by integrating the TRAIL gene into an oncolytic vector. EXPERIMENTAL
      DESIGN: We constructed a TRAIL-expressing oncolytic adenovector designated as
      Ad/TRAIL-E1. The expression of both the TRAIL and viral E1A genes is under the
      control of a synthetic promoter consisting of sequences from the human telomerase
      reverse transcriptase promoter and a minimal cytomegalovirus early promoter. The
      transgene expression, apoptosis induction, viral replication, antitumor activity,
      and toxicity of Ad/TRAIL-E1 were determined in vitro and in vivo in comparison
      with control vectors. RESULTS: Ad/TRAIL-E1 elicited enhanced viral replication
      and/or stronger oncolytic effect in vitro in various human cancer cell lines than
      a TRAIL-expressing, replication-defective adenovector or an oncolytic adenovector
      expressing green fluorescent protein. Intralesional administration of Ad/TRAIL-E1
      eliminated all s.c. xenograft tumors established from a human non-small cell lung
      cancer cell line, H1299, on nu/nu nude mice, resulting in long-term, tumor-free
      survival. Furthermore, we found no treatment-related toxicity. CONCLUSIONS: Viral
      replication and antitumor activity of oncolytic adenovirus can be enhanced by the
      TRAIL gene and Ad/TRAIL-E1 could become a potent therapeutic agent for cancer
      therapy.

PMID- 16951243
TI  - Preclinical characterization of AEG35156/GEM 640, a second-generation antisense
      oligonucleotide targeting X-linked inhibitor of apoptosis.
AB  - PURPOSE: Cancer cells can use X-linked inhibitor of apoptosis (XIAP) to evade
      apoptotic cues, including chemotherapy. The antitumor potential of AEG35156, a
      novel second-generation antisense oligonucleotide directed toward XIAP, was
      assessed in human cancer models when given as a single agent and in combination
      with clinically relevant chemotherapeutics. EXPERIMENTAL DESIGN: AEG35156 was
      characterized for its ability to cause dose-dependent reductions of XIAP mRNA and
      protein in vitro and in vivo, to sensitize cancer cell lines to death stimuli,
      and to exhibit antitumor activity in multiple human cancer xenograft models as a
      single agent or in combination with chemotherapy. RESULTS: AEG35156 reduced XIAP
      mRNA levels with an EC50 of 8 to 32 nmol/L and decreased XIAP protein levels by
      >80%. Loss of XIAP protein correlated with increased sensitization to tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in
      Panc-1 pancreatic carcinoma cells. AEG35156 exhibited potent antitumor activity
      relative to control oligonucleotides in three human cancer xenograft models
      (prostate, colon, and lung) and was capable of inducing complete tumor regression
      when combined with taxanes. Antitumor effects of AEG35156 correlated with
      suppression of tumor XIAP levels. CONCLUSIONS: AEG35156 reduces XIAP levels and
      sensitizes tumors to chemotherapy. AEG35156 is presently under clinical
      assessment in multiple phase I trials in cancer patients as a single agent and in
      combination with docetaxel in solid tumors or cytarabine/idarubicin in leukemia.

PMID- 16951244
TI  - Effect of raloxifene on the incidence of invasive breast cancer in postmenopausal
      women with osteoporosis categorized by breast cancer risk.
AB  - PURPOSE: To assess the effect of raloxifene, indicated for osteoporosis treatment
      and prevention, on invasive breast cancer in subgroups of postmenopausal women
      defined by risk factors for breast cancer. EXPERIMENTAL DESIGN: Data from the 4
      year Multiple Outcomes of Raloxifene Evaluation (MORE) trial (N=7,705) and a
      follow-up study, the 4-year Continuing Outcomes Relevant to Evista (CORE) trial
      (N=4,011), were analyzed. Prespecified subgroups were defined by age (>or=65
      versus<65 years), age at menopause (>or=49 versus<49 years), body mass index
      (>or=25 versus<25 kg/m2), family history of breast cancer (yes/no), serum
      estradiol level (5-10 versus<5, >10 versus<5 pmol/L), prior estrogen therapy
      (yes/no), and bone mass at MORE baseline, and 5-year predicted risk, assessed
      using the modified Gail model (>or=1.67 versus<1.67%), at CORE baseline. Time-to
      first invasive breast cancer was analyzed using Cox proportional hazards models.
      RESULTS: In the placebo group, older age, higher estradiol level, and a family
      history of breast cancer were associated with an increased breast cancer risk
      (P<0.05). Raloxifene therapy was associated with a reduced breast cancer risk in
      both women at lower and those at higher breast cancer risk. Hazard ratio point
      estimates were 0.11 to 0.67, corresponding to a 33% to 89% reduction in breast
      cancer risk with raloxifene versus placebo. The therapy by family history
      interaction was significant (P=0.04). CONCLUSIONS: Raloxifene therapy was
      associated with a reduced risk of invasive breast cancer in postmenopausal women
      irrespective of the presence/absence of risk factors; its effect was greater in
      women with a family history of breast cancer.

PMID- 16951245
TI  - Liver intestine-cadherin (CDH17) haplotype is associated with increased risk of
      hepatocellular carcinoma.
AB  - PURPOSE: Hepatocellular carcinoma (HCC), the most common form of liver cancer, is
      a leading cause of cancer death worldwide. We previously showed that aberrant
      mRNA splicing of the liver intestine-cadherin gene CDH17 in liver tissues was
      triggered by the specific constellation of two CDH17 single nucleotide
      polymorphisms (651T and IVS6+35G). CDH17 aberrant splicing was highly associated
      with tumor dissemination and shorter survival of HCC patients. Consequently, it
      is highly relevant to assess whether the presence of these single nucleotide
      polymorphisms in the general population represents a risk to the development of
      HCC. EXPERIMENTAL DESIGN: We conducted a case-control study including 164 HCC and
      99 cirrhosis patients and 293 healthy controls. Genotyping was done by PCR and
      direct sequencing. Odds ratio (OR) and chi2 analysis were used to analyze
      genotypes and haplotypes. RESULTS: Genotypes 651TT [OR, 2.62; 95% confidence
      interval (95% CI), 1.34-5.03] and IVS6+35 GG (OR, 1.95; 95% CI, 1.04-3.62) were
      highly associated with HCC disease. The 651T (C>T) and IVS6+35G (A>G) alleles
      were also overrepresented in HCC patients and, in particular, the T-G haplotype
      was the most prevalent in HCC patients when compared with healthy controls (OR,
      1.57; 95% CI, 1.167-2.109; P=0.004), which was in agreement with the aberrant
      splicing observed in tumor tissues. There was no significant difference in
      genotype and allele frequencies between cirrhosis patients and controls.
      CONCLUSION: The functional T-G haplotype of CDH17 (651 C>T and IVS6+35A>G) is a
      genetic susceptibility factor for the development of HCC in a Chinese population.

PMID- 16951246
TI  - Mononuclear infiltrates in osteosarcoma and chemokine receptor expression.

PMID- 16951248
TI  - Stretching to meet needs: integrin-linked kinase and the cardiac pump.

PMID- 16951249
TI  - When viral oncoprotein meets tumor suppressor: a structural view.

PMID- 16951250
TI  - Modulating the outer membrane with small RNAs.
AB  - MicF, one of the first chromosomally encoded regulatory small RNAs (sRNAs) to be
      discovered, was found to modulate the expression of OmpF, an abundant outer
      membrane protein. Several recent papers have now shown that this is not an
      isolated case. At least five other sRNAs also regulate the synthesis of outer
      membrane porins, and additional sRNAs modulate the expression of other outer
      membrane proteins. Here we review what is known about these sRNAs and discuss the
      implications of this regulation.

PMID- 16951251
TI  - CTCF mediates long-range chromatin looping and local histone modification in the
      beta-globin locus.
AB  - CTCF (CCCTC-binding factor) binds sites around the mouse beta-globin locus that
      spatially cluster in the erythroid cell nucleus. We show that both conditional
      deletion of CTCF and targeted disruption of a DNA-binding site destabilize these
      long-range interactions and cause local loss of histone acetylation and gain of
      histone methylation, apparently without affecting transcription at the locus. Our
      data demonstrate that CTCF is directly involved in chromatin architecture and
      regulates local balance between active and repressive chromatin marks. We
      postulate that throughout the genome, relative position and stability of CTCF
      mediated loops determine their effect on enhancer-promoter interactions, with
      gene insulation as one possible outcome.

PMID- 16951252
TI  - Targeted ablation of ILK from the murine heart results in dilated cardiomyopathy
      and spontaneous heart failure.
AB  - A requirement for integrin-mediated adhesion in cardiac physiology is revealed
      through targeted deletion of integrin-associated genes in the murine heart. Here
      we show that targeted ablation of the integrin-linked kinase (ILK) expression
      results in spontaneous cardiomyopathy and heart failure by 6 wk of age. Deletion
      of ILK results in disaggregation of cardiomyocytes, associated with disruption of
      adhesion signaling through the beta1-integrin/FAK (focal adhesion kinase)
      complex. Importantly, the loss of ILK is accompanied by a reduction in cardiac
      Akt phosphorylation, which normally provides a protective response against
      stress. Together, these results suggest that ILK plays a central role in
      protecting the mammalian heart against cardiomyopathy and failure.

PMID- 16951253
TI  - Crystal structure of SV40 large T-antigen bound to p53: interplay between a viral
      oncoprotein and a cellular tumor suppressor.
AB  - The transformation potential of Simian Virus 40 depends on the activities of
      large T-antigen (LTag), which interacts with several cellular tumor suppressors
      including the important "guardian" of the genome, p53. Inhibition of p53 function
      by LTag is necessary for both efficient viral replication and cellular
      transformation. We determined the crystal structure of LTag in complex with p53.
      The structure reveals an unexpected hexameric complex of LTag binding six p53
      monomers. Structure-guided mutagenesis of LTag and p53 residues supported the p53
      LTag interface defined by the complex structure. The structure also shows that
      LTag binding induces dramatic conformational changes at the DNA-binding area of
      p53, which is achieved partially through an unusual "methionine switch" within
      p53. In the complex structure, LTag occupies the whole p53 DNA-binding surface
      and likely interferes with formation of a functional p53 tetramer. In addition,
      we showed that p53 inhibited LTag helicase function through direct complex
      formation.

PMID- 16951254
TI  - Proteolysis of MLL family proteins is essential for taspase1-orchestrated cell
      cycle progression.
AB  - Taspase1 was identified as the threonine endopeptidase that cleaves mixed-lineage
      leukemia (MLL) for proper Hox gene expression in vitro. To investigate its
      functions in vivo, we generated Taspase1(-/-) mice. Taspase1 deficiency results
      in noncleavage (nc) of MLL and MLL2 and homeotic transformations. Remarkably, our
      in vivo studies uncover an unexpected role of Taspase1 in the cell cycle.
      Taspase1(-/-) animals are smaller in size. Taspase1(-/-) mouse embryonic
      fibroblasts (MEFs) exhibit impaired proliferation, and acute deletion of Taspase1
      leads to a marked reduction of thymocytes. Taspase1 deficiency incurs down
      regulation of Cyclin Es, As, and Bs and up-regulation of p16(Ink4a) . We show
      that MLL and MLL2 directly target E2Fs for Cyclin expression. The uncleaved
      precursor MLL displays a reduced histone H3 methyl transferase activity in vitro.
      Accordingly, chromatin immunoprecipitation assays demonstrate a markedly
      decreased histone H3 K4 trimethylation at Cyclin E1 and E2 genes in Taspase1(-/-)
      cells. Furthermore, MLL(nc/nc;2nc/nc) MEFs are also impaired in proliferation.
      Our data are consistent with a model in which precursor MLLs, activated by
      Taspase1, target to Cyclins through E2Fs to methylate histone H3 at K4, leading
      to activation. Lastly, Taspase1(-/-) cells are resistant to oncogenic
      transformation, and Taspase1 is overexpressed in many cancer cell lines. Thus,
      Taspase1 may serve as a target for cancer therapeutics.

PMID- 16951255
TI  - S. pombe CLASP needs dynein, not EB1 or CLIP170, to induce microtubule
      instability and slows polymerization rates at cell tips in a dynein-dependent
      manner.
AB  - The Schizosaccharomyces pombe CLIP170-associated protein (CLASP) Peg1 was
      identified in a screen for mutants with spindle formation defects and a screen
      for molecules that antagonized EB1 function. The conditional peg1.1 mutant
      enabled us to identify key features of Peg1 function. First, Peg1 was required to
      form a spindle and astral microtubules, yet destabilized interphase microtubules.
      Second, Peg1 was required to slow the polymerization rate of interphase
      microtubules that establish end-on contact with the cortex at cell tips. Third,
      Peg1 antagonized the action of S. pombe CLIP170 (Tip1) and EB1 (Mal3). Fourth,
      although Peg1 resembled higher eukaryotic CLASPs by physically associating with
      both Mal3 and Tip1, neither Tip1 nor Mal3 was required for Peg1 to destabilize
      interphase microtubules or for it to associate with microtubules. Conversely,
      neither Mal3 nor Tip1 required Peg1 to associate with microtubules or cell tips.
      Consistently, while mal3.Delta and tip1.Delta disrupted linear growth, corrupting
      peg1 (+) did not. Fifth, peg1.1 phenotypes resembled those arising from deletion
      of the single heavy or both light chains of fission yeast dynein. Furthermore,
      all interphase phenotypes arising from peg1 (+) manipulation relied on dynein
      function. Thus, the impact of S. pombe CLASP on interphase microtubule behavior
      is more closely aligned to dynein than EB1 or CLIP170.

PMID- 16951256
TI  - Interplay between Ino80 and Swr1 chromatin remodeling enzymes regulates cell
      cycle checkpoint adaptation in response to DNA damage.
AB  - Ino80 and Swr1 are ATP-dependent chromatin remodeling enzymes that have been
      implicated in DNA repair. Here we show that Ino80 is required for cell cycle
      checkpoint adaptation in response to a persistent DNA double-strand break (DSB).
      The failure of cells lacking Ino80 to escape checkpoint arrest correlates with an
      inability to maintain high levels of histone H2AX phosphorylation and an
      increased incorporation of the Htz1p histone variant into chromatin surrounding
      the DSB. Inactivation of Swr1 eliminates this DNA damage-induced Htz1p
      incorporation and restores H2AX phosphorylation and checkpoint adaptation. We
      propose that Ino80 and Swr1 function antagonistically at chromatin surrounding a
      DSB, and that they regulate the incorporation of different histone H2A variants
      that can either promote or block cell cycle checkpoint adaptation.

PMID- 16951257
TI  - A novel genetic hierarchy functions during hypaxial myogenesis: Pax3 directly
      activates Myf5 in muscle progenitor cells in the limb.
AB  - We address the molecular control of myogenesis in progenitor cells derived from
      the hypaxial somite. Null mutations in Pax3, a key regulator of skeletal muscle
      formation, lead to cell death in this domain. We have developed a novel allele of
      Pax3 encoding a Pax3-engrailed fusion protein that acts as a transcriptional
      repressor. Heterozygote mouse embryos have an attenuated mutant phenotype, with
      partial conservation of the hypaxial somite and its myogenic derivatives,
      including some hindlimb muscles. At these sites, expression of Myf5 is
      compromised, showing that Pax3 acts genetically upstream of this myogenic
      determination gene. We have characterized a 145-base-pair (bp) regulatory
      element, at -57.5 kb from Myf5, that directs transgene expression to the mature
      somite, notably to myogenic cells of the hypaxial domain that form ventral trunk
      and limb muscles. A Pax3 consensus site in this sequence binds Pax3 in vitro and
      in vivo. Multimers of the 145-bp sequence direct transgene expression to sites of
      Pax3 function, and an assay of its activity in the chick embryo shows Pax3
      dependence. Mutation of the Pax3 site abolishes all expression controlled by the
      145-bp sequence in transgenic mouse embryos. We conclude that Pax3 directly
      regulates Myf5 in the hypaxial somite and its derivatives.

PMID- 16951259
TI  - Estrogenic agonist activity of ICI 182,780 (Faslodex) in hippocampal neurons:
      implications for basic science understanding of estrogen signaling and
      development of estrogen modulators with a dual therapeutic profile.
AB  - The present study sought to determine the characteristics of ICI 182,780
      (Faslodex) action in rat primary hippocampal neurons. We first investigated the
      neuroprotective efficacy of ICI 182,780 against neurodegenerative insults
      associated with Alzheimer's disease and related disorders. Dose-response analyses
      revealed that ICI 182,780, in a concentration-dependent manner, significantly
      promoted neuron survival following exposure to either excitotoxic glutamate (200
      muM)- or beta-amyloid(1-42) (1.5 muM)-induced neurodegeneration of hippocampal
      neurons. At a clinically relevant concentration of 50 ng/ml, ICI 182,780 exerted
      nearly maximal neuroprotection against both insults with efficacy comparable with
      that induced by the endogenous estrogen 17beta-estradiol. Thereafter, we
      investigated the impact of 50 ng/ml ICI 182,780 on mechanisms of 17beta-estradiol
      inducible neuronal plasticity and neuroprotection. Results of these analyses
      demonstrated that ICI 182,780 directly induced a series of rapid intracellular
      Ca(2+) concentration ([Ca(2+)](i)) oscillations in a pattern comparable with that
      of 17beta-estradiol. In addition, ICI 182,780 exerted dual regulation of the
      glutamate-induced rise in [Ca(2+)](i) identical to that induced by 17beta
      estradiol. Further analyses demonstrated that ICI 182,780 induced significant
      activation of extracellular signal-regulated kinase 1/2 and Akt (protein kinase
      B) and significantly increased expression of spinophilin and Bcl-2, with efficacy
      comparable with neurons treated with 17beta-estradiol. Taken together, results of
      these in vitro analyses of ICI 182,780 provide direct evidence of an estrogenic
      agonist profile of ICI 182,780 action in rat hippocampal neurons. Therapeutic
      development of neuroselective estrogen receptor modulators that mimic ICI 182,780
      is discussed with respect to the potential of safe and efficacious alternatives
      to estrogen therapy for the prevention of postmenopausal cognitive decline and
      late-onset Alzheimer's disease.

PMID- 16951258
TI  - The zinc-finger factor Insm1 (IA-1) is essential for the development of
      pancreatic beta cells and intestinal endocrine cells.
AB  - The pancreatic and intestinal primordia contain epithelial progenitor cells that
      generate many cell types. During development, specific programs of gene
      expression restrict the developmental potential of such progenitors and promote
      their differentiation. The Insm1 (insulinoma-associated 1, IA-1) gene encodes a
      Zinc-finger factor that was discovered in an insulinoma cDNA library. We show
      that pancreatic and intestinal endocrine cells express Insm1 and require Insm1
      for their development. In the pancreas of Insm1 mutant mice, endocrine precursors
      are formed, but only few insulin-positive beta cells are generated. Instead,
      endocrine precursor cells accumulate that express none of the pancreatic
      hormones. A similar change is observed in the development of intestine, where
      endocrine precursor cells are formed but do not differentiate correctly. A
      hallmark of endocrine cell differentiation is the accumulation of proteins that
      participate in secretion and vesicle transport, and we find many of the
      corresponding genes to be down-regulated in Insm1 mutant mice. Insm1 thus
      controls a gene expression program that comprises hormones and proteins of the
      secretory machinery. Our genetic analysis has revealed a key role of Insm1 in
      differentiation of pancreatic and intestinal endocrine cells.

PMID- 16951260
TI  - Protein kinase A-mediated phosphorylation contributes to enhanced contraction
      observed in mice that overexpress beta-adrenergic receptor kinase-1.
AB  - Transgenic mice with cardiac specific overexpression of beta-adrenergic receptor
      kinase-1 (betaARK-1) exhibit reduced contractility in the presence of adrenergic
      stimulation. However, whether contractility is altered in the absence of
      exogenous agonist is not clear. Effects of betaARK-1 overexpression on
      contraction were examined in mouse ventricular myocytes, studied at 37 degrees C,
      in the absence of adrenergic stimulation. In myocytes voltage-clamped with
      microelectrodes (18-26 MOmega; 2.7 M KCl) to minimize intracellular dialysis,
      contractions were significantly larger in betaARK-1 cells than in wild-type
      myocytes. In contrast, when cells were dialyzed with patch pipette solution (1-3
      MOmega; 0 mM NaCl, 70 mM KCl, 70 mM potassium aspartate, 4 mM MgATP, 1 mM
      MgCl(2), 2.5 mM KH(2)PO(4), 0.12 mM CaCl(2), 0.5 mM EGTA, and 10 mM HEPES), the
      extent of cell shortening was similar in wild-type and betaARK-1 myocytes.
      Furthermore, when cells were dialyzed with solutions that contained
      phosphodiesterase-sensitive sodium-cAMP (50 microM), the extent of cell
      shortening was similar in wild-type and betaARK-1 myocytes. However, when patch
      solutions were supplemented with phosphodiesterase-resistant 8-bromo-cAMP (50
      muM), contractions were larger in betaARK-1 than wild-type cells. This difference
      was eliminated by the protein kinase A inhibitor N-[2-(4
      bromocinnamylamino)ethyl]-5-isoquinoline (H89). Interestingly, Ca(2+) current
      amplitudes and inactivation rates were similar in betaARK-1 and wild-type cells
      in all experiments. These results suggest components of the adenylyl cyclase
      protein kinase A pathway are sensitized by chronically increased betaARK-1
      activity, which may augment contractile function in the absence of exogenous
      agonist. Thus, changes in contractile function in myocytes from failing hearts
      may reflect, in part, effects of chronic up-regulation of betaARK-1 on the cAMP
      protein kinase A pathway.

PMID- 16951261
TI  - Is overnight tube feeding associated with hypoxia in stroke?

PMID- 16951262
TI  - Atrial myxoma presenting as transient ischaemic attack and acute coronary
      syndrome in an octogenarian.

PMID- 16951263
TI  - Favourable effects of exercise training on N-terminal pro-brain natriuretic
      peptide plasma levels in elderly patients after acute myocardial infarction.
AB  - BACKGROUND: regional or global impairment of left ventricular (LV) systolic or
      diastolic function leading to increased LV wall stress results in increased
      circulating levels of N-terminal pro-brain natriuretic peptide (NT-pro-BNP).
      OBJECTIVE: this study aims at evaluating the effect of exercise training (ET) on
      NT-pro-BNP plasma levels in older patients recovering from acute myocardial
      infarction (AMI). DESIGN: prospective randomised study. SETTING: Academic Medical
      Centre. SUBJECTS: forty older patients (33 males and 7 females) who experienced
      AMI. METHODS: patients were randomised into two groups, each composed of 20
      patients: Group A were enrolled in a 3-month exercise-based cardiac
      rehabilitation (CR) programme and Group B were discharged home with generic
      instructions to continue physical activity. NT-pro-BNP, cardiopulmonary and
      Doppler-echocardiographic parameters were measured at baseline and at 3-month
      follow-up. RESULTS: in Group A, ET reduced NT-pro-BNP levels (from 1446 +/- 475
      to 435 +/- 251 pg/ml, P<0.001) and increased maximal exercise parameters; there
      was also an inverse correlation between changes in NT-pro-BNP levels and in
      VO(2peak) (r = -0.67, P<0.01), E-wave (r = -0.42, P<0.01) and E/A ratio (r = 
      0.60, P<0.01). In Group B, after 3 months, no changes were observed in NT-pro-BNP
      levels, exercise and echocardiographic parameters. LV volumes and left
      ventricular ejection fraction (LVEF) were unchanged after 3 months in both
      groups. CONCLUSIONS: three months ET in older patients after AMI was associated
      with a reduction in NT-pro-BNP levels and an overall improvement of exercise
      capacity, without negative LV remodelling and with improvement in early LV
      filling. Further investigation is required to evaluate whether in these patients
      the reduction of NT-pro-BNP levels at 3 months could be useful as a surrogate
      marker of favourable LV remodelling at a later follow-up.

PMID- 16951264
TI  - Enhancing the pathologist's role at hospital tumor boards.
AB  - Recommendations are proposed to enhance the role of the pathologist in the
      hospital-based tumor conference (tumor board). The modifications focus on two
      components integral to the conference: the presentation of salient pathologic
      features of each tumor selected for discussion within the time constraints
      allotted, and the pathologist's role as a principal institutional educator with
      respect to neoplastic processes. Opportunities to utilize conference
      presentations as a resource in other educational settings are also considered.

PMID- 16951265
TI  - Interpreting hair mercury levels in individual patients.
AB  - Evaluation of mercury exposure in an individual patient ideally includes the
      presenting history, physical examination, consideration of the differential
      diagnosis, and mercury analysis of blood and urine specimens. Analysis of mercury
      in hair specimens may supply useful supplemental information about exposure to
      organic compounds such as methylmercury, particularly to help reconstruct the
      pattern of prior exposure. The most appropriate specimen is generally terminal
      type hair from the occipital-neck junction, clamped to maintain strand alignment,
      and oriented to the scalp. Hair from the initial 0.5 cm adjacent to the scalp
      represents on average 1-3 wk before collection, and consideration of the time
      frame represented by the specimen is an important part of the evaluation.
      Literature reports describe hair mercury levels as high as 2400 microg/g. Hair
      mercury level is usually <1 microg/g in individuals who do not eat fish but may
      be >30 microg/g in those who frequently consume fish with high mercury content.
      Hair mercury level is often not correlated with blood mercury concentration or
      symptoms of mercury toxicity, and reports of hair contamination by exogenous
      mercury are not uncommon. Hair mercury level is notoriously prone to
      misinterpretation and should be used with an understanding of its limitations.

PMID- 16951266
TI  - Plasma eosinophil cationic protein, interleukin-5, and ECP/Eo count ratio in
      patients with various eosinophilic diseases.
AB  - Hypereosinophilia is associated with clonal disorders, reactive conditions, and
      rarely with idiopathic hypereosinophilic syndrome (IHES). We investigated whether
      measurement of eosinophilic activity using the plasma eosinophil cationic protein
      (ECP) level, interleukin-5 (IL-5) level, and the ratio of eosinophilic cationic
      protein/eosinophil count (ECP/Eo) could improve the early differentiation among
      various eosinophilic diseases: IHES (n = 9), clonal disorder (n = 35), reactive
      eosinophilia with malignancy (n = 30), and reactive eosinophilia with
      inflammation (n = 46). The 120 eosinophilic patients had higher plasma ECP and IL
      5 levels than the non-eosinophilic control group (p <0.05). The 9 patients with
      IHES had significantly higher plasma ECP and IL-5 levels than patients with other
      eosinophilic diseases (p <0.05). The plasma levels of ECP and the ECP/Eo ratio
      were higher in patients with non-haematologic malignancy than in those with other
      reactive eosinophilias (p <0.05). This study shows that levels of plasma ECP, IL
      5, and ECP/Eo ratio may assist in the clinical differentiation of various
      eosinophilic diseases.

PMID- 16951267
TI  - Increased serum neopterin levels in women with polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) occurs in 5-10% of premenopausal women. Studies
      suggest that PCOS is associated with increased risk of coronary heart disease
      (CHD). To investigate this relationship, 15 PCOS women (group 1) and 10 healthy
      women (group 2) were studied. Blood leukocyte counts (white blood cells, WBC) and
      serum levels of total cholesterol, HDL-cholesterol, LDL-cholesterol, sensitive C
      reactive protein (sCRP), and neopterin were measured in the 2 groups. There were
      no significant differences in serum total cholesterol, HDL-cholesterol, or LDL
      cholesterol concentrations between groups 1 and 2. Blood WBC counts and serum
      levels of neopterin and sCRP were significantly higher in group 1 than group 2.
      The median (min-max) levels were: WBC, group 1: 8.05 (5.10-9.70) cells x 10(9)/L,
      group 2: 6.25 (4.70-9.70) cells x 10(9)/L (p <0.01); neopterin, group 1: 10.6
      (7.5-49.5) nmol/L, group 2: 9.6 (6.5-12.9) nmol/L (p < 0.05); and sCRP, group 1:
      7.0 (1.2-12.0) mg/L, group 2: 2.0 (0.1-12.0) mg/L (p <0.01). This study shows
      that blood WBC counts and serum sCRP and neopterin levels are significantly
      elevated in women with PCOS. These findings support an increased risk for early
      onset cardiovascular disease in women with PCOS. This is the first report that
      women with PCOS have higher serum neopterin levels than healthy women with
      regular menstrual cycles.

PMID- 16951269
TI  - Morphoproteomic and molecular concomitants of an overexpressed and activated mTOR
      pathway in renal cell carcinomas.
AB  - CCI-779 (temsirolimus), an ester of rapamycin and an inhibitor of the mammalian
      target of rapamycin (mTOR), is currently in phase II trials for treatment of
      patients with solid cancers. The mTOR functions as a checkpoint for cell
      proliferation, with upstream Akt and downstream p70S6K serving as its most
      important mediators. The aim of this study was to evaluate the expression and
      activation of the Akt-mTOR-p70S6K pathway in renal cell carcinoma (RCC), seeking
      to strengthen the rationale for targeted therapy of RCC using rapamycin or a
      rapamycin analogue. Tissue microarray sections containing 128 primary RCCs, 22
      metastatic RCCs, and 24 non-neoplastic (normal) kidneys (NK) were immunostained
      with monoclonal antibodies to phosphorylated (p)-Akt (Ser473), p-mTOR (Ser2448),
      and p-p70S6K (Thr389). Western blotting was performed on 3 cases of clear cell
      RCC (CRCC) and the corresponding non-neoplastic (normal) renal tissues using the
      same antibodies. The immunostain scoring system included: (a) location; (b)
      distribution; and (c) intensity. The normal kidneys provided baseline scores for
      comparison. Expression of p-Akt, p-mTOR, and p-p70S6K was seen in 100% (n = 24)
      of NKs and nearly 100% (n = 150) of both primary and metastatic RCCs. The p
      p70S6K was located in the nucleus in both NKs and RCCs. The p-Akt was observed in
      the nucleus and cytoplasm of NKs and in the nucleus and cytoplasm/ membrane
      (plasmalemma) of RCCs. The p-mTOR was identified in the membrane of NKs and the
      membrane/nucleus of RCCs. The levels of expression of p-p70S6K, p-mTOR, and p-Akt
      were significantly higher in RCC than in NK in the overall pattern (intensity and
      distribution, p <0.05). Western blotting also showed higher expression of p
      p70S6K, p-mTOR, and p-Akt in RCCs compared to the corresponding normal kidney
      tissues (p <0.05). These findings indicate that correlative over-expression and
      activation of p-Akt, p-mTOR, and p-p70S6K are commonly observed in RCCs. After
      considering these findings in the context of other established protein
      circuitries and pathways in RCC, we propose therapeutic approaches that
      incorporate rapamycin-like agents and other small molecule inhibitors in a
      combinatorial fashion in future clinical trials for RCC.

PMID- 16951268
TI  - Morphoproteomic and pharmacoproteomic rationale for mTOR effectors as therapeutic
      targets in head and neck squamous cell carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) has a relatively high mortality
      rate and poor prognosis. Recently, we showed that overexpression of
      phosphorylated (p) nuclear factor-kappaB (NF-kappaB) in squamous cell carcinoma
      of the tonsil (SCCT) and high grade dysplasia is associated with a poor
      prognosis. Because the mammalian target of the rapamycin (mTOR) pathway
      contributes to the activation of NF-kappaB through immunophilin/mTOR signaling,
      we investigated: (a) the immunohistochemical expression and state of activation
      and potential clinical significance of components of the mTOR signal transduction
      pathway in SCCT patients (morphoproteomics); and (b) the inhibitory effects of
      rapamycin on the growth and state of activation of mTOR in 2 HNSCC cell lines
      (pharmacoproteomics). Archival biopsy materials from 39 patients with SCCT were
      studied by immunohistochemistry for the expression of p-mTOR (Ser 2448), and p
      p70S6K (Thr 389), and/or cyclin D1. Results for SCCT were compared with adjacent
      non-neoplastic epithelium, when present, and with normal tonsillar epithelium
      from approximately age-matched controls; clinical outcomes were also assessed.
      SCCT showed mTOR (Ser 2448) expression in 93% (30/32 cases) with 2+ or 3+
      plasmalemmal and/or cytoplasmic intensity in 84% vs 42% in surface epithelium
      from normal tonsils (p <0.001). The mean combined expression score (signal
      intensity x percentage of positive cells) for p-p70S6K was significantly greater
      in the SCCT group vs adjacent non-neoplastic squamous epithelium and normal
      tonsillar epithelium of the control group (p <0.05). A relationship existed
      between higher p-p70S6K expression levels in the non-neoplastic squamous
      epithelium adjacent to the SCCT and increased risk of death from disease (hazard
      ratio = 7.9; 95% confidence interval (CI) = 2.1 to 29.9; p = 0.002). There was
      also a relationship between nuclear expression of cyclin D1 in SCCT and shortened
      recurrence-free survival (p = 0.015). Two human HNSCC cell lines, SCC-15 and
      FaDu, were incubated with and without rapamycin to assess its impact on growth
      and on the expression of p-mTOR. Rapamycin in a dose-dependent fashion inhibited
      growth more in SCC-15, which correlated with a greater reduction in
      constitutively activated p-mTOR (Ser 2448) as shown by Western blotting. In
      conclusion, these morphoproteomic and pharmacoproteomic data collectively provide
      a rationale for selecting mTOR effectors as therapeutic targets in HNSCC.

PMID- 16951270
TI  - Rapid fecal cytokeratin-19 test and fecal occult blood test in screening for
      gastrointestinal diseases.
AB  - To evaluate the screening power of the fecal cytokeratin-19 test (CK-19) and the
      fecal occult blood test (FOBT), we performed rapid fecal CK-19 and FOBT tests on
      515 stool samples from patients with various GI diseases and 814 stool samples
      from control patients. The rapid fecal CK-19 test (developed by DiNonA Research
      Institute, Seoul, Korea) is based on gold immunochromatography and has a
      sensitivity of 1 ng/ml. The positive rate of the FOBT was 2.1% in controls, 14.0%
      in GI cancer patients, 3.5% in GI inflammation patients, 11.7% in bone marrow
      transplant (BMT) patients, and 6.0% in childhood diarrhea patients. Except for
      the GI inflammation patients, the patients' positive rates for FOBT were all
      higher than the controls (p <0.05). The positive rate of the fecal CK-19 test was
      8.2% in controls, 42.1% in GI cancer patients, 66.0% in GI inflammation patients,
      84.8% in BMT patients, and 19.9% in childhood diarrhea patients. In all of the
      patient groups, positive rates for the CK-19 test were higher than in the
      controls (p <0.05). The fecal CK-19 test was more frequently positive (42.1%) in
      GI cancer patients than the FOBT; if both tests were used, the sensitivity was
      49.1%. The fecal CK-19 test (but not the FOBT) gave a higher positive rate in GI
      inflammation patients than the controls, suggesting that the CK-19 test could
      serve as a screening test for GI inflammation. The highest positive rate of the
      fecal CK-19 test was found in the BMT group, indicating that significant GI
      epithelial desquamation had occurred. Although the positive rate of the fecal CK
      19 test in childhood diarrhea patients was higher than in the controls, it was
      much lower than in adults with GI inflammatory disease. Evidently, children with
      GI inflammation do not desquamate as much intestinal epithelium as adult patients
      with GI inflammation. This study shows that the rapid fecal GK-19 test, used in
      conjunction with the FOBT, may be a valuable screening technique for GI diseases
      and can assist physicians in the differential diagnosis of GI diseases.

PMID- 16951271
TI  - Plasma BNP and NT-proBNP assays by automated immunoanalyzers: analytical and
      clinical study.
AB  - The plasma concentrations of natriuretic peptides, BNP and NTproBNP, have been
      shown to be markers for the diagnosis of congestive heart failure (CHF). In this
      study, plasma BNP and NTproBNP concentrations were evaluated and stratified
      according to renal function, body mass index (BMI), and New York Heart
      Association (NYHA) classification. Comparison studies between the 2 natriuretic
      peptide markers were performed. Assays for BNP were performed with a Triage
      reagent pack (Biosite, Inc) on an Access 2 immunoanalyzer (Beckman-Coulter);
      NTproBNP assays were performed with a Roche reagent pack on an Elecsys 20.10
      immunoanalyzer (Roche Diagnostics). Plasma samples were collected from
      consecutive patients hospitalized for cardiac disorders at our institution.
      Nonparametric tests were used for statistical analyses. The results show that
      alterations of renal function had less impact on BNP (p = 0.9) than on NTproBNP
      concentrations (p <0.0001). BNP and NTproBNP levels were lower in obese patients
      with CHF (515 +/- 61 ng/L and 1652 +/- 124 ng/L, respectively) than in lean
      patients (900 +/- 85 ng/L and 6686 +/- 749 ng/L). Although NTproBNP levels
      averaged about 10 times higher than BNP levels, there was significant correlation
      between these 2 markers (Deming regression r2 = 0.40, IC: 0.95). In conclusion,
      plasma BNP and NTproBNP assays are both useful for the diagnosis of CHF and left
      ventricular dysfunction. However, renal function and obesity must be taken into
      account for clinical interpretation. These assays have good analytical
      performance and the choice between them depends on local preference.

PMID- 16951272
TI  - Effect of sodium hydroxybutyrate on the expression of hippocampal N-methyl-D
      aspartate receptor 2B subunit mRNA in neonatal rats with hypoxic-ischemic insult.
AB  - The objective of this research was to test whether sodium hydroxybutyrate (GHB
      Na) protects rat neonatal brain against hypoxia-ischemia (HI). Specifically, the
      objective was to determine the effect of GHB-Na administration on the expression
      of N-methyl-D-aspartate subunit (NR2B) mRNA in the rat hippocampus. Seven-day-old
      Sprague-Dawley rats were subjected to ligation of the left carotid artery and
      were randomly assigned to 5 groups: sham operated (S), saline treated (C), and
      those treated with GHB-Na (G1, G2, G3), at 3 dosages (50, 100, or 200 mg/kg, ip,
      thrice daily). NR2B mRNA levels in the left hippocampus were assayed at 2, 6, 12,
      24, 72, and 168 hr after HI (exposure to 8% O(2)/92% N atmosphere for 2 hr). The
      results suggest that HI insult increased NR2B mRNA gene expression in the left
      hippocampus of the neonatal rats and that GHB-Na administration partially
      suppressed this effect of HI insult.

PMID- 16951273
TI  - L-carnitine reduces cochlear damage induced by gamma irradiation in Guinea pigs.
AB  - L-carnitine (LC) protects cells from peroxidative damage. In this study, we
      tested whether L-carnitine (LC) prevents radiation-induced cochlear damage after
      total cranial irradiation (radiotherapy; RT). Male albino guinea pigs were
      randomly distributed in 3 groups. The Control group (n = 11) received neither LC
      nor irradiation, but saline solution ip and sham irradiation for 5 days. The RT
      group (n = 32) received saline solution ip as placebo therapy and exposure to
      total cranial irradiation of 33 Gy in 5 fractions of 6.6 Gy/day on 5 successive
      days, with a calculated (alpha/beta = 3.5) biological effective dose of
      fractionated irradiation equal to 60 Gy conventional fractionation. The LC + RT
      group (n = 36) received total cranial irradiation, plus LC (100 mg/kg/day, ip)
      for 5 days. The guinea pigs were killed at 4, 24, or 96 hr after the last dose of
      RT and the cochleas were enucleated for histopathologic examination. There was no
      cochlear degeneration in the control group. In the RT group, total cranial
      irradiation caused degeneration in stria vascularis (SV), spiral ganglion (SG),
      outer hair cells (OHC), and inner hair cells (IHC) of cochleas at 4, 24, and 96
      hr. In the LC + RT group, LC administration reduced radiation-induced cochlear
      degeneration in SV and SG at 4, 24, and 96 hr, and in OHC and IHC at 24 and 96 hr
      (p <0.05). Thus, this study shows that L-carnitine can ameliorate radiation
      induced cochlear damage in guinea pigs.

PMID- 16951274
TI  - Chronic active thrombotic microangiopathy in native and transplanted kidneys.
AB  - We report 2 complicated cases of thrombotic microangiopathy with chronic features
      and active components. The first case was a 36-yr-old woman with positive anti
      DNA antibody and possible lupus cerebritis, who developed thrombotic
      microangiopathy secondary to a series of syndromes, including preeclampsia and
      anti-phospholipid antibody syndrome. Renal biopsy revealed no evidence of lupus
      nephritis and her renal function returned to normal 1 week after the biopsy. The
      second case was a 46-yr-old man who developed thrombotic microangiopathy of
      unknown etiology, which led to end-stage renal disease within 6 mo. The patient
      received a living related-donor transplant, but thrombotic microangiopathy
      recurred in the donor kidney only 40 days after the renal transplantation.

PMID- 16951275
TI  - An Angiotensin-converting enzyme inhibitor, zofenopril, prevents renal
      ischemia/reperfusion injury in rats.
AB  - Zofenopril ameliorates experimental cardiac ischemia/reperfusion (IR) injury in
      animal models and exhibits beneficial cardiovascular effects in patients with
      myocardial infarction. The objective of the present research was to investigate
      whether zofenopril can protect against renal IR injury. Rats were divided into 4
      experimental groups: (a) control, (b) IR (60 min of ischemia followed by 24 hr of
      reperfusion), (c) zofenopril (15 mg/kg/day for 2 days), and (d) zofenopril+IR.
      All of the rats underwent right nephrectomy, and the rats in the IR and
      zofenopril+IR groups also underwent IR.then the left kidneys were removed for
      biochemical analyses and microscopic examination. There were no abnormalities in
      the biochemical and microscopic findings in the preoperative right kidneys. The
      lipid peroxidation, protein oxidation, and nitric oxide levels as well as
      xanthine oxidase and myeloperoxidase activities were increased and the catalase
      and superoxide dismutase activities were decreased in the IR group; zofenopril
      treatment prevented these changes (p <0.05). In the IR group, the kidney sections
      showed severe acute tubular damage including brush border loss, nuclear
      condensation, cytoplasmic swelling, and loss of nuclei; in the zofenopril+IR
      group, the normal glomerular morphology was preserved and there was slight edema
      of the tubular cells. The renal damage score was significantly reduced in the
      zofenopril+IR group vs the IR group (p <0.05). In conclusion, IR injury caused
      oxidative damage in renal tissue and zofenopril prevented this IR injury.

PMID- 16951276
TI  - Experimental ischemic cardiomyopathy: insights into remodeling, physiological
      adaptation, and humoral response.
AB  - Ligation of the left anterior descending coronary artery (LAD) is used to induce
      experimental myocardial infarction (MI). Most previous studies have focused on
      the early postoperative period, while data on mid-term follow-up are scanty. This
      study examined the mid-term effects of LAD ligation in 95 MI rats and 28
      controls. The following parameters were evaluated: systemic blood pressure (SBP),
      heart rate (HR), and plasma brain natriuretic peptide (BNP) level. In addition, M
      mode and B-mode echocardiography, histologic examinations, and cardiac
      hydroxyproline assays were performed. Forty-seven perioperative and 5 late deaths
      were recorded. Left ventricular dilation, observed 1 mo after MI, did not
      progress with time. Septal thickening was similar in the 2 groups, while wall
      thickening was lower in the MI rats at 1 mo only. Stroke volume was diminished in
      MI rats, while cardiac output was depressed only at 1 and 2 mo, due to increased
      heart rate. SBP was unchanged and plasma BNP level was similar in the 2 groups.
      The infarcted area (mean +/- SD) was 35 +/- 10%. The ventricles in MI rats were
      heavier and had increased hydroxyproline content. In conclusion, these data show
      that LAD ligation is not only a model of acute MI, but at mid-term it provides a
      model of chronic ischemic dilated cardiomyopathy.

PMID- 16951277
TI  - An in vitro culturing model for rabbit dural cells.
AB  - The objectives of this study were (a) to construct an in vitro model of rabbit
      dural healing, (b) to test the influence of collagen, laminin, and poly-L-lysine
      on the migration and proliferation of dural cells, and (c) to study the healing
      mechanism of duraplasty. Rabbit dural pieces (1.5 cm x 1.5 cm) were perforated in
      their central part with a 2 mm punch to mimic a dural defect. The dural pieces
      were cultured in 24-well plates that had been coated with collagen, laminin, or
      poly-L-lysine, and the influence of different extracellular matrices on migration
      and proliferation of dural cells was observed. Cells were subcultured on slides
      for immunocytochemistry to study their characteristics; dural healing was
      observed by scanning electron microscopy. The results demonstrated that only the
      dural pieces that were cultured on collagen-coated wells showed migration of
      cells into the central defect after a period of 8 to 10 days and that healing of
      the dural defect occurred by 13 to 15 days. The cultured dural cells stained
      strongly positive with an antibody to vimentin, but negative with an antibody to
      factor VIII. New collagen fibers were observed in the dural defects. This report
      demonstrates that an in vitro model for dural healing was successfully
      constructed in collagen-coated wells; the results implicate cellular migration of
      fibroblasts from the dural defect margin as an important mechanism of wound
      healing following duraplasty.

PMID- 16951278
TI  - Experimentally-induced acute lung injury: the protective effect of hydroxyethyl
      starch.
AB  - The objective of this study was to evaluate the effects of hydroxyethyl starch,
      (130/0.4) 6%, compared to Ringer's acetate and modified gelatin on hypoxemia,
      inflammatory response, and oxidative stress in an experimental model of acute
      lung injury (ALI). The ALI/Adult Respiratory Distress Syndrome (ARDS)
      experimental model was produced by a bronchoalveolar saline lavage. Mature New
      Zealand white rabbits were anesthetized, provided with a tracheostomy and
      vascular catheters, and randomized to receive 25 ml/kg/hr of Ringer's acetate
      (group R, n = 7), 25 ml/kg/hr of modified gelatin (group G, n = 7), or 25
      ml/kg/hr of hydroxyethyl starch (group S, n = 7). All of the rabbits received
      mechanical ventilation to maintain the PaCO2 between 35 and 45 mm Hg. Blood gas
      levels and hemodynamic values were recorded before induction of lung injury (T0)
      and 10 (T10), 120 (T120) and 240 (T240) min following induction of lung injury.
      At the same time-points, blood samples were collected to measure the plasma
      levels of TNFalpha (tumor necrosis factor-alpha) and TBARS (thiobarbituric acid
      reactive substances). The experiment yielded the following results: The blood
      PaO2/FiO2 ratio was higher in group S than in groups R and G at T10, T120, and
      T240 (p <0.05). In group S, the plasma TNFalpha and TBARS concentrations were
      lower than in groups R and G at T120 and T240 (p <0.05). In conclusion, rabbits
      treated with hydroxyethyl starch, (130/0.4) 6%, demonstrated reductions of
      hypoxemia, inflammatory response, and oxidative lung damage, compared to raabbits
      treated with Ringer's acetate or modified gelatin.

PMID- 16951279
TI  - Plasma lipoprotein(a) levels and LDL-cholesterol lowering response to statin
      therapy in patients with heterozygous familial hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) is characterised by elevated plasma LDL
      cholesterol levels and premature ischemic heart disease. Statin therapy is
      mandatory in order to prevent atherosclerosis in patients with heterozygous FH.
      Both genetic and environmental factors affect the statin-induced LDL-cholesterol
      lowering effect in patients with heterozygous FH. Recently published data suggest
      that plasma lipoprotein(a) levels may affect the efficacy of statin therapy in
      patients with nephrotic syndrome. However, no data are available concerning the
      effect of lipoprotein(a) levels on the efficacy of statin therapy in patients
      with heterozygous FH. This report demonstrates negative correlation between
      plasma lipoprotein(a) levels and the LDL-cholesterol lowering effect of statin
      therapy in 49 patients with heterozygous FH.

PMID- 16951280
TI  - Combination of serum transferrin receptor and red cell distribution width for
      assessing anemia in patients with chronic diseases.

PMID- 16951281
TI  - Rediscoveries in pathology and laboratory medicine.

PMID- 16951283
TI  - Patient misconceptions and ethical challenges in radioactive iodine scanning and
      therapy.
AB  - The use and nature of radioactive iodine (RAI) are complex topics for patients
      with thyroid conditions to understand. Fear and anxiety over its use,
      misinformation in patient advocacy books and on the Internet, medical jargon,
      confusion regarding postscanning and posttreatment procedures, patient literacy,
      thyroid health status, and several other socioeconomic factors can create serious
      barriers to genuine informed consent in RAI scanning and treatment. The following
      discussion will review the origins of patient misconceptions and
      misinterpretations, including international differences in physician attitudes
      regarding RAI usage. Next, this article will present the core ethical duties,
      problems, and moral dilemmas that can arise in the RAI setting. Upon completion
      of this article, the reader should be able to describe the core ethical
      principles of respect for persons (patient autonomy), beneficence,
      nonmaleficence, and justice; describe the 3 components of informed consent;
      identify common barriers to informed consent and describe how such barriers can
      lead to misconceptions, misinformation, and refusal of treatment with RAI; and
      summarize where RAI candidates and patients first look for information and
      identify the common ways in which misinformation surfaces.

PMID- 16951284
TI  - Usefulness of medium-energy collimator for sentinel node lymphoscintigraphy
      imaging in breast cancer patients.
AB  - This study was performed to investigate the usefulness of a general-purpose
      medium-energy (ME) collimator for the accurate localization of the sentinel lymph
      node (SLN) in breast cancer patients. METHODS: We compared phantom images and
      lymphoscintigraphy images obtained under different conditions for a patient with
      breast cancer. Comparisons were performed between 2 cameras, between a low-energy
      high-resolution (LEHR) collimator and a general-purpose ME collimator, and
      between energy windows centered at 141 keV and at 146 keV. Profile curves and
      image contrast were evaluated along with the visual interpretation of images. The
      most suitable imaging time was selected from the relationship between contrast
      and the data acquisition time. RESULTS: The images obtained with the general
      purpose ME collimator and the energy window centered at 141 keV were of poorer
      quality than those obtained with the LEHR collimator and the same energy window.
      However, the quality of the images obtained with the general-purpose ME
      collimator improved when the energy window was centered at 146 keV. The method
      involving the general-purpose ME collimator and the energy window centered at 146
      keV showed excellent image quality similar to that obtained with the LEHR
      collimator. The enhancement of contrast was confirmed at more than 3 cm away from
      the center of the injection site. Stable contrast was obtained with a data
      acquisition time of 5 min, with the general-purpose ME collimator, and with the
      energy window centered at 146 keV. CONCLUSION: The method involving the general
      purpose ME collimator and the energy window centered at 146 keV has the merit of
      the lymph node not being concealed by a lead shield. This new method is expected
      to improve the rate of detection of SLN and has the potential for shortening the
      acquisition time.

PMID- 16951285
TI  - Improved detection and localization of lower gastrointestinal tract hemorrhage by
      subtraction scintigraphy: phantom analysis.
AB  - Acute lower gastrointestinal tract hemorrhage (LGIH) has significant morbidity
      and mortality outcomes. Although several causes of LGIH can be life threatening,
      most can be effectively treated; therefore, early detection and accurate
      localization of bleeding sites are critical for successful patient management.
      METHODS: This study was a phantom experimental study with a repeated-measures
      design. The minimum detectable bleeding rate, the minimum detectable bleed
      volume, the sensitivity for detection, and the time required for detection were
      determined and compared for conventional scintigraphy (CS) and 3 experimental
      techniques: reference subtraction scintigraphy (RSS), sequential subtraction
      scintigraphy (SSS), and alternate sequential subtraction scintigraphy (ASSS).
      RESULTS: The minimum detectable bleeding rates within the first hour were 0.05
      mL.min-1 for CS and RSS, 0.1 mL.min-1 for ASSS, and 0.5 mL.min-1 for SSS. This
      study demonstrated minimum detectable bleed volumes of 2.2 mL for CS, 2.3 mL for
      RSS, 5 mL for ASSS, and 5 mL for SSS stratified to a "definitely present"
      certainty. No statistically significant difference was noted in the mean time to
      detection between CS and the subtraction techniques. Receiver-operating
      characteristic analysis indicated that combining CS and RSS improved test
      performance and increased overall sensitivity to 75% from 68.3% for CS and 71.7%
      for RSS. CONCLUSION: Supplementing conventional datasets with RSS and ASSS may
      provide a useful tool that combines the advantages offered for lesion
      detectability by a high-contrast 99mTc-sulfur colloid study with the window of
      opportunity offered by 99mTc-labeled red blood cell scanning.

PMID- 16951286
TI  - Finger doses for staff handling radiopharmaceuticals in nuclear medicine.
AB  - Radiation doses to the fingers of occupational workers handling 99mTc-labeled
      compounds and 131I for diagnostic and therapeutic procedures in nuclear medicine
      were measured by thermoluminescence dosimetry. METHODS: The doses were measured
      at the base of the ring finger and the index finger of both hands in 2 groups of
      workers. Group 1 (7 workers) handled 99mTc-labeled radiopharmaceuticals, and
      group 2 (6 workers) handled 131I for diagnosis and therapy. Radiation doses to
      the fingertips of 3 workers also were measured. Two were from group 1, and 1 was
      from group 2. RESULTS: The doses to the base of the fingers for the radiopharmacy
      staff and physicians from group 1 were observed to be 17+/-7.5 (mean+/-SD) and
      13.4+/-6.5 microSv/GBq, respectively. Similarly, the dose to the base of the
      fingers for the 3 physicians in group 2 was estimated to be 82.0+/-13.8
      microSv/GBq. Finger doses for the technologists in both groups could not be
      calculated per unit of activity because they did not handle the
      radiopharmaceuticals directly. Their doses were reported in millisieverts that
      accumulated in 1 wk. The doses to the fingertips of the radiopharmacy worker and
      the physician in group 1 were 74.3+/-19.8 and 53.5+/-21.9 microSv/GBq,
      respectively. The dose to the fingertips of the physician in group 2 was 469.9+/
      267 microSv/GBq. CONCLUSION: The radiation doses to the fingers of nuclear
      medicine staff at our center were measured. The maximum expected annual dose to
      the extremities appeared to be less than the annual limit (500 mSv/y), except for
      a physician who handled large quantities of 131I for treatment. Because all of
      these workers are on rotation and do not constantly handle radioactivity
      throughout the year, the doses to the base of the fingers or the fingertips
      should not exceed the prescribed annual limit of 500 mSv.

PMID- 16951287
TI  - Rapid determination of the radiochemical purity of 99mTc-antimony trisulfide
      colloid prepared by standard and alternative heating methods.
AB  - The purpose of this study was to validate a rapid quality control method for the
      lymphoscintigraphic tracer 99mTc-antimony trisulfide colloid (99mTc-ATC).
      METHODS: ATC was labeled with 99mTc according to the manufacturer's instructions
      as well as by alternative heating conditions designed to provide a range of
      percentages of radiochemical purity (RCP): the tracer was prepared in a dry block
      heater with heating cavities of different sizes, the temperature of the heating
      block was varied from 70 degrees C to 115 degrees C, or the duration of heating
      was varied from 15 to 35 min. Anion-exchange minicolumns were trialled to
      separate any 99mTc-pertechnetate impurity from 99mTc-ATC with physiologic saline
      as the eluent. Quality control results were compared with the results from the
      manufacturer's recommended method, which uses an instant thin-layer
      chromatography (ITLC) strip with saline as the migrating solution. RESULTS: The
      quality control results obtained with a cartridge method in 2-3 min compared
      favorably with those obtained with the ITLC method with saline when the tracer
      was prepared by heating at 115 degrees C in a dry block heater for 35 min (RCPs,
      99.4%+/-0.3% [mean+/-SD] and 99.2%+/-0.3%, respectively; n=25). The cartridge and
      ITLC quality control results also were in excellent agreement (correlation
      coefficient, 0.99) over a range of RCPs (80%-100%). An alternative anion-exchange
      cartridge that was tested in this study was not suitable for assaying the RCP of
      99mTc-ATC because of the complete retention of 99mTc-pertechnetate on the
      sorbent. CONCLUSION: Compared with the established ITLC method, the cartridge
      quality control method tested in this study is rapid and provides a reliable
      assessment of the RCP of 99mTc-ATC. For the preparation of 99mTc-ATC, a dry block
      heater can be successfully substituted for a boiling water bath and is
      recommended for heating at high altitudes.

PMID- 16951288
TI  - Simplified method for determining the radiochemical purity of 99mTc-MAG3.
AB  - 99mTc-Mercaptoacetyltriglycine is used for dynamic renal imaging, and the summary
      of product characteristics (SPC) for the European formulation specifies a shelf
      life of 1 or 4 h, depending on the reconstitution volume of the kit. To minimize
      the time required to test the radiochemical purity, a simplified quality control
      method was developed. METHODS: To satisfy the recommendations of the
      International Commission on Harmonisation, results obtained with the methods
      described in the European and American SPCs were compared with those obtained
      with the simplified method. Further validation of the new method was performed by
      comparison with the standard 2-strip thin-layer chromatographic method as well as
      tests for linearity and limits of detection and quantification. RESULTS: The
      simplified method provided results comparable to those provided by the registered
      SPC methods but was more rapid to perform and used smaller volumes of solvents.
      CONCLUSION: The simplified method is a reasonable alternative to the registered
      SPC methods.

PMID- 16951289
TI  - Targeting chromosomal sites with locked nucleic acid-modified triplex-forming
      oligonucleotides: study of efficiency dependence on DNA nuclear environment.
AB  - Triplex-forming oligonucleotides (TFOs) are synthetic DNA code-reading molecules
      that have been demonstrated to function to some extent in chromatin within cell
      nuclei. Here we have investigated the impact of DNA nuclear environment on the
      efficiency of TFO binding. For this study we have used locked nucleic acid
      containing TFOs (TFO/LNAs) and we report the development of a rapid PCR-based
      method to quantify triplex formation. We have first compared triplex formation on
      genes located at different genomic sites and containing the same
      oligopyrimidine*oligopurine sequence. We have shown that efficient TFO binding is
      possible on both types of genes, expressed and silent. Then we have further
      investigated when gene transcription may influence triplex formation in
      chromatin. We have identified situations where for a given gene, increase of
      transcriptional activity leads to enhanced TFO binding: this was observed for
      silent or weakly expressed genes that are not or are only slightly accessible to
      TFO. Such a transcriptional dependence was observed for integrated and endogenous
      loci, and chemical and biological activations of transcription. Finally, we
      provide evidence that TFO binding is sequence-specific as measured on mutated
      target sequences and that up to 50% of chromosomal targets can be covered by the
      TFO/LNA in living cells.

PMID- 16951290
TI  - EASI--enrichment of alternatively spliced isoforms.
AB  - Alternative splicing produces more than one protein from the majority of genes
      and the rarer forms can have dominant functions. Instability of alternative
      transcripts can also hinder the study of regulation of gene expression by
      alternative splicing. To investigate the true extent of alternative splicing we
      have developed a simple method of enriching alternatively spliced isoforms (EASI)
      from PCRs using beads charged with Thermus aquaticus single-stranded DNA-binding
      protein (T.Aq ssb). This directly purifies the single-stranded regions of
      heteroduplexes between alternative splices formed in the PCR, enabling direct
      sequencing of all the rare alternative splice forms of any gene. As a proof of
      principle the alternative transcripts of three tumour suppressor genes, TP53,
      MLH1 and MSH2, were isolated from testis cDNA. These contain missing exons,
      cryptic splice sites or include completely novel exons. EASI beads are stable for
      months in the fridge and can be easily combined with standard protocols to speed
      the cloning of novel transcripts.

PMID- 16951291
TI  - A locally adaptive statistical procedure (LAP) to identify differentially
      expressed chromosomal regions.
AB  - MOTIVATION: The systematic integration of expression profiles and other types of
      gene information, such as chromosomal localization, ontological annotations and
      sequence characteristics, still represents a challenge in the gene expression
      arena. In particular, the analysis of transcriptional data in context of the
      physical location of genes in a genome appears promising in detecting chromosomal
      regions with transcriptional imbalances often characterizing cancer. RESULTS: A
      computational tool named locally adaptive statistical procedure (LAP), which
      incorporates transcriptional data and structural information for the
      identification of differentially expressed chromosomal regions, is described. LAP
      accounts for variations in the distance between genes and in gene density by
      smoothing standard statistics on gene position before testing the significance of
      their differential levels of gene expression. The procedure smooths parameters
      and computes p-values locally to account for the complex structure of the genome
      and to more precisely estimate the differential expression of chromosomal
      regions. The application of LAP to three independent sets of raw expression data
      allowed identifying differentially expressed regions that are directly involved
      in known chromosomal aberrations characteristic of tumors. AVAILABILITY:
      Functions in R for implementing the LAP method are available at
      http://www.dpci.unipd.it/Bioeng/Publications/LAP.htm

PMID- 16951292
TI  - Harm resulting from inappropriate telephone triage in primary care.
AB  - PURPOSE: Our objective was to assess and categorize harm occurring to patients
      who called their physicians' office after-hours but did not have their call
      forwarded to the physician because they stated that their call was not an
      emergency. METHODS: We collected data on 4949 calls handled by our answering
      service for 1 year in a family medicine residency office in Denver, CO. Of the
      2835 after-hours clinical calls, we reviewed all 288 clinical calls that were not
      forwarded to the "on-call" physician. Complete data on 119 clinical calls
      included reason for call, frequency of next day appointments, Emergency
      Department visits, hospital admissions and outcomes. Outcomes were reviewed and
      coded for harm to the patient by experienced medical errors coders. RESULTS: When
      patient calls were not forwarded, 51% had an appointment, 4% an Emergency
      Department visit, and 2% were admitted to the hospital within 2 weeks. Analysis
      revealed that 3% suffered harm, and 26% experienced discomfort due to the delay.
      Although 66% required no intervention, 1% required emergency transport and 4% a
      medication change. CONCLUSIONS: Harm may occur when patients' calls are not
      forwarded to the on-call physician. Although the level of harm is generally
      temporary and minimal, the potential exists for serious harm to occur. Physicians
      need to re-evaluate the way they handle after-hours calls.

PMID- 16951293
TI  - Effects of using free sample medications on the prescribing practices of family
      physicians.
AB  - INTRODUCTION: We determined whether family physicians (FPs) who distribute free
      sample medications are more likely to prescribe those medications than physicians
      who do not. METHODS: We reviewed administrative health plan prescription data of
      three similar clinics with 23 FPs within a comprehensive health care delivery
      system. Only clinic X physicians dispensed free sample medications. To determine
      which prescribed medications to study, the sample medications log from clinic X
      was categorized. The 25 sample medications most frequently dispensed by category
      were selected as study medications. Outcome measures included the number,
      proportion, cost, and formulary status of study medications prescribed and the
      average 30-day prescription costs. RESULTS: Physicians at clinic X prescribed the
      largest proportion of prescriptions for study medications, the smallest
      proportion of preferred name brands among study medications, and had the highest
      costs for prescriptions of non-listed formulary study medications (P < .0001).
      The average 30-day prescription costs differed significantly by clinic (P <
      .0001), with clinic X being the highest. There was a significant association
      between the number of samples dispensed and the number of prescriptions written
      for study medications by physicians at clinic X (P = .006). CONCLUSIONS: Our data
      support the conclusion that FPs who distribute free samples are more likely to
      prescribe those medications than their counterparts who do not.

PMID- 16951294
TI  - Effectiveness of targeted anticipatory guidance during well-child visits: a pilot
      trial.
AB  - INTRODUCTION: Anticipatory guidance, an important function of well-child visits,
      is often brief and not tailored to parents' concerns. This targeted pilot trial
      evaluated a new method of anticipatory guidance. METHODS: Using an
      experimental/control study design, we surveyed 137 parents and 31 physicians,
      comparing their responses to targeted anticipatory guidance (physician-provided
      education based on parents' concerns) versus usual anticipatory guidance
      (standard physician lecture on parenting, safety, and nutritional topics).
      RESULTS: Overall, physicians appeared less satisfied than parents with the
      educational component of well-child visits, and they desired changes in the
      educational aspect of these visits. While physicians believed the targeted
      approach was easier, control group parents appeared more satisfied with usual
      anticipatory guidance. The number of anticipatory guidance topics covered in the
      control group was less than half of that covered in the experimental group.
      CONCLUSIONS: Our targeted method of anticipatory guidance during well-child
      visits covered more educational topics and resulted in visits that were easier
      for physicians, but less satisfactory for parents. Further research is needed to
      identify methods of anticipatory guidance that are effective and satisfactory for
      both parents and physicians.

PMID- 16951295
TI  - The fish in secondary prevention of heart disease (FISH) survey--primary care
      physicians and omega3 fatty acid prescribing behaviors.
AB  - PURPOSE: Consumption of fish oil has been shown to reduce mortality in patients
      with cardiovascular disease (CVD). This study aims to determine the frequency and
      associations of dietary fish prescribing by family physicians. METHODS: A 22-item
      survey mailed to randomly selected Washington State family physicians. RESULTS:
      Nearly all agreed that nutrition is important in CVD prevention (99%) and felt
      that they have an essential role in giving dietary advice (92%). The majority
      (57%) knew of fish oil's effectiveness in secondary prevention of CVD. However,
      only 17% of respondents were identified as high fish prescribers. Knowledge of
      fish oil's benefit in sudden death reduction was associated with higher fish
      prescribers in bivariate (P = .005) and multivariate analysis (OR = 2.77; 95th
      CI: 1.32 to 5.82). High fish prescribers were more likely to report having
      sufficient time to discuss dietary therapies in bivariate (P = .018) and
      multivariate analysis (OR = 1.43; 95th CI: 1.03 to 1.98). CONCLUSIONS: Despite
      knowledge of fish oil's benefit and favorable attitudes toward nutritional
      therapy, family physicians infrequently recommend fish oils for their CVD
      patients. Strategies improving awareness of fish oil's effects on sudden death
      and reducing time barriers associated with dietary counseling should be explored
      further to increase recommendation of this important advice.

PMID- 16951296
TI  - Cancer risk assessment: examining the family physician's role.
AB  - BACKGROUND: Cancer risk assessment begins in the primary care clinician's office.
      Essential components of that process include: 1) documentation of personal and
      family cancer information; 2) identification of families at increased risk for
      cancer; 3) modification of cancer screening recommendations according to degree
      of risk; 4) referral of high-risk individuals to cancer genetics clinics. The
      purpose of this study was to examine these 4 components of primary care cancer
      risk assessment using data abstracted from patient records at an academic family
      medicine center. METHODS: Ambulatory records of 734 patients were reviewed in
      their entirety for information relevant to cancer risk assessment. Detail of
      cancer information was categorized as comprehensive, adequate, or inadequate.
      Patient records were categorized as suggestive of average, moderate, or high
      genetic risk for cancer. For patients with a family history of colorectal cancer,
      modification of colon cancer screening to reflect degree of cancer risk was
      assessed. Finally, the frequency of cancer genetic referral in high-risk
      individuals was noted. RESULTS: The presence or absence of a family history of
      cancer was documented in 97.8% of records. There was insufficient information to
      adequately assess risk in 69.5% of charts. Detail of family cancer documentation
      was associated with personal history of cancer (P = .001), patient age (P =
      .001), and physician training status (P = .042), but not with patient or
      physician gender, duration of care, or completion of a genogram. For persons with
      a family history of colorectal cancer, compliance with cancer screening
      individualized to degree of risk was achieved in 50% of patients. Ten patients
      met criteria for moderate or high genetic risk for cancer. None had been offered
      cancer genetics consultation. CONCLUSIONS: Nearly all records documented the
      presence or absence of a family history of cancer. However, in those with a
      positive family history, the detail of information was insufficient to permit
      risk assessment in over two thirds of individuals; risk-stratified colon cancer
      screening was not achieved in half of the patients with a family history of
      colorectal cancer; individuals at moderate or high cancer risk were not
      identified as such; and those at high risk were not offered cancer genetics
      referral. In addition to collecting adequate family cancer information, family
      physicians need to adopt explicit risk assessment criteria to identify, and to
      optimally care for, those at increased genetic risk for cancer.

PMID- 16951297
TI  - Primary medication adherence in a rural population: the role of the patient
      physician relationship and satisfaction with care.
AB  - INTRODUCTION: Although correlates of overall medication adherence have been
      studied, little is known about primary medication non-adherence-patients' failing
      to fill a prescription provided by a practitioner-and whether it relates to how
      patients view their physician, satisfaction with their care, and how easy or hard
      it is for them to travel for care. METHODS: This study uses telephone survey data
      from adults in 150 rural counties in 8 southeastern states. Bivariate and
      multivariable analyses were used to identify factors associated with adults' self
      reports of delaying or not filling prescriptions. RESULTS: Of the 3926
      respondents who had received care in the previous year, 894 (21.6%) reported that
      they had delayed or did not fill a prescription over that time. In multivariate
      analysis, delaying or not filling prescriptions was more common among respondents
      who were under age 65, African American, reported incomes less than 25,000
      dollars, and reported fair or poor health. Non-adherence was also more common
      among patients who reported transportation problems, a lack of confidence in
      their doctor's ability to help them, a lack of satisfaction with the concern
      shown them by their physicians, and a lack of satisfaction with how welcome and
      comfortable they are made to feel by office staff. CONCLUSIONS: Prescription
      primary non-adherence is prevalent in the rural South. Adherence may be improved
      by remedying patient dissatisfaction and lack of confidence in their physicians
      as well as addressing transportation barriers.

PMID- 16951298
TI  - Exercise and restless legs syndrome: a randomized controlled trial.
AB  - BACKGROUND AND OBJECTIVES: Restless legs syndrome (RLS) is a common,
      underdiagnosed neurological movement disorder of undetermined etiology. The
      primary treatments for restless legs syndrome are pharmacological. To date, no
      randomized controlled trials have examined the effectiveness of an exercise
      program on the symptoms of RLS. METHODS: Study participants (N = 41) were
      randomized to either exercise or control groups. 28 participants (average age
      53.7; 39% males) were available and willing to begin the 12-week trial. The
      exercise group was prescribed a conditioning program of aerobic and lower-body
      resistance training 3 days per week. Restless legs symptoms were assessed by the
      International RLS Study Group (IRLSSG) severity scale and an ordinal scale of RLS
      severity at the beginning of the trial, and at 3, 6, 9, and 12 weeks. RESULTS:
      Twenty-three participants completed the trial. At the end of the 12 weeks, the
      exercise group (N = 11) had a significant improvement in symptoms compared with
      the control group (N = 12) (P = .001 for the IRLSSG severity scale and P < .001
      for the ordinal scale). CONCLUSIONS: The prescribed exercise program was
      effective in improving the symptoms of RLS.

PMID- 16951299
TI  - Preventing alcohol-exposed pregnancies.
AB  - Fetal alcohol exposure affects approximately 1% to 3% of live births in the
      United States. Family physicians are in a unique position to reduce the incidence
      of alcohol-exposed pregnancy. Fetal alcohol exposure can be minimized through 2
      general approaches: reducing alcohol consumption or increasing effective
      contraception among childbearing-aged women who engage in "at-risk" drinking and
      encouraging pregnant women to abstain from alcohol. Although no safe level of
      alcohol consumption during pregnancy is established, women who binge drink are
      more likely to deliver infants with physical and cognitive-developmental
      anomalies. Screening tools, such as quantity/frequency questions, the TWEAK and
      the T-ACE, developed specifically for prenatal care, are more useful with women
      than the CAGE and Michigan Alcohol Screening Test (MAST). Screening alone seems
      to reduce alcohol use among pregnant women. Brief interventions, including
      education about alcohol's effects on the developing fetus, are effective among
      women not responding to screening. Unfortunately, many barriers exist to
      effective implementation of alcohol-exposed pregnancy (AEP) prevention in the
      clinical setting. Designing effective office base systems so the entire burden of
      implementing AEP prevention activities does fall solely on the family physician
      is critical.

PMID- 16951300
TI  - Practice facilitators and practice-based research networks.
AB  - Practice facilitators (PFs) are health care professionals, who assist primary
      care practices in research and quality improvement activities. Their work goes
      beyond data collection and feedback and includes practice enhancement methods to
      facilitate system-level changes. PFs provide a framework for translating research
      into practice by building relationships, improving communication, facilitating
      change, and sharing resources in practice-based research networks (PBRNs). The
      work of PFs is funded from a variety of sources, including academic grants and
      renewable contracts with national, state, and local health care agencies. Limited
      information is available on cost-effectiveness of PF interventions. This article
      provides examples of how the PF model was implemented in 4 PBRNs in the United
      States.

PMID- 16951301
TI  - Revisiting swallowed troubles: intestinal complications caused by two magnets--a
      case report, review and proposed revision to the algorithm for the management of
      foreign body ingestion.

PMID- 16951302
TI  - Tenderness over the hyoid bone can indicate epiglottitis in adults.
AB  - Adult acute epiglottitis is a rare but life-threatening disease caused by
      obstruction of the airway. The symptoms and signs of this disease may be
      nonspecific without apparent airway compromise. We encountered 3 consecutive
      cases of adult patients with this disease in a single 5-month period in one
      physician's office. In all cases, physical examination revealed tenderness of the
      anterior neck over the hyoid bone. These observations assisted us in identifying
      this rare disease quickly. We suggest that tenderness over the hyoid bone should
      raise suspicion of adult acute epiglottitis.

PMID- 16951303
TI  - Horner's syndrome and trigeminal nerve palsy following epidural analgesia for
      labor.
AB  - Epidural analgesia is a widely used method of pain control in the labor and
      delivery setting but is not without risks. We present a case of Horner's syndrome
      and trigeminal nerve palsy as a rare complication of epidural analgesia in an
      obstetric patient. Although reported in few instances in the anesthesia
      literature, awareness among providers in obstetrics is critical because this
      could be the first sign of a high sympathetic blockade resulting in potential
      maternal-fetal morbidity.

PMID- 16951304
TI  - Pedometers as a means to increase walking and achieve weight loss.

PMID- 16951305
TI  - Prevalence and type of band name fast food at academic-affiliated hospitals.

PMID- 16951306
TI  - Inappropriate lack of stratification by elective or emergency operation status
      and missing information on important confounders.

PMID- 16951307
TI  - Family mealtime interactions and overweight children with asthma: potential for
      compounded risks?
AB  - OBJECTIVE: Exploratory study aimed to examine differences in family interaction
      patterns during a routine mealtime between overweight, at-risk for overweight,
      and average weight children with asthma. METHODS: Eighty families of children
      with asthma, aged 5-12 years, were videotaped during a mealtime in their homes.
      The videotapes were rated using the McMaster Mealtime Family Interaction Coding
      System (MICS). Structural aspects of the meal such as presence of sugary drinks
      and whether the television was on were also coded. RESULTS: Significant
      differences were found on the MICS with families of children with asthma who were
      overweight scoring lower on task accomplishment, affect management, interpersonal
      involvement, and roles. Families of overweight children with asthma also
      displayed an increased presence of sugary beverages, shorter meal length, and
      fewer adults at the table. CONCLUSIONS: Preliminary findings suggest that
      families with children with asthma who are overweight may have a more difficult
      time managing mealtimes and feel overwhelmed by this family routine.

PMID- 16951308
TI  - Nucleotide-binding oligomerization domain-like receptors: intracellular pattern
      recognition molecules for pathogen detection and host defense.
AB  - The nucleotide binding oligomerization domain-like receptor (NLR) family of
      pattern recognition molecules is involved in a diverse array of processes
      required for host immune responses against invading pathogens. Unlike TLRs that
      mediate extracellular recognition of microbes, several NLRs sense pathogens in
      the cytosol and upon activation induce host defense signaling pathways. Although
      TLRs and NLRs differ in their mode of pathogen recognition and function, they
      share similar domains for microbial sensing and cooperate to elicit immune
      responses against the pathogen. Genetic variation in several NLR genes is
      associated with the development of inflammatory disorders or increased
      susceptibility to microbial infection. Further understanding of NLRs should
      provide critical insight into the mechanisms of host defense and the pathogenesis
      of inflammatory diseases.

PMID- 16951309
TI  - Cutting edge: TLR9 and TLR2 signaling together account for MyD88-dependent
      control of parasitemia in Trypanosoma cruzi infection.
AB  - Activation of innate immune cells by Trypanosoma cruzi-derived molecules such as
      GPI anchors and DNA induces proinflammatory cytokine production and host defense
      mechanisms. In this study, we demonstrate that DNA from T. cruzi stimulates
      cytokine production by APCs in a TLR9-dependent manner and synergizes with
      parasite-derived GPI anchor, a TLR2 agonist, in the induction of cytokines by
      macrophages. Compared with wild-type animals, T. cruzi-infected Tlr9(-/-) mice
      displayed elevated parasitemia and decreased survival. Strikingly, infected Tlr2(
      /-)Tlr9(-/-) mice developed a parasitemia equivalent to animals lacking MyD88, an
      essential signaling molecule for most TLR, but did not show the acute mortality
      displayed by MyD88(-/-) animals. The enhanced susceptibility of Tlr9(-/-) and
      Tlr2(-/-)Tlr9(-/-) mice was associated with decreased in vivo IL-12/IFN-gamma
      responses. Our results reveal that TLR2 and TLR9 cooperate in the control of
      parasite replication and that TLR9 has a primary role in the MyD88-dependent
      induction of IL-12/IFN-gamma synthesis during infection with T. cruzi.

PMID- 16951310
TI  - Cutting edge: TREM-2 attenuates macrophage activation.
AB  - The triggering receptor expressed on myeloid cells 2 (TREM-2) delivers
      intracellular signals through the adaptor DAP12 to regulate myeloid cell function
      both within and outside the immune system. The role of TREM-2 in immunity has
      been obscured by the failure to detect expression of the TREM-2 protein in vivo.
      In this study, we show that TREM-2 is expressed on macrophages infiltrating the
      tissues from the circulation and that alternative activation with IL-4 can induce
      TREM-2. TREM-2 expression is abrogated by macrophage maturation with LPS of IFN
      gamma. Using TREM-2(-/-) mice, we find that TREM-2 functions to inhibit cytokine
      production by macrophages in response to the TLR ligands LPS, zymosan, and CpG.
      Furthermore, we find that TREM-2 completely accounts for the increased cytokine
      production previously reported by DAP12(-/-) macrophages. Taken together, these
      data show that TREM-2 is expressed on newly differentiated and alternatively
      activated macrophages and functions to restrain macrophage activation.

PMID- 16951311
TI  - Leishmania antigens are presented to CD8+ T cells by a transporter associated
      with antigen processing-independent pathway in vitro and in vivo.
AB  - CD8+ T cells are generated in response to Leishmania major (Lm) or Toxoplasma
      gondii parasitic infections, indicating that exogenously delivered Ag can be
      processed for presentation by MHC class I molecules. We show that presentation of
      Lm nucleotidase (NT)-OVA is TAP independent in vivo and in vitro, and is
      inhibited by chloroquine, but not by proteasome inhibitors. In contrast, the
      presentation of T. gondii P30-OVA relies on the TAP/proteasome pathway.
      Presentation of OVA- or rNT-OVA-coated beads also bypassed TAP requirement above
      a certain Ag threshold. TAP was also dispensable for the presentation of wild
      type Lm Ags to primed CD8+ T cells in vitro. Finally, in vivo priming of CD8+ T
      cells involved in acquired resistance to Lm was not compromised in TAP-deficient
      mice. Thus, Leishmania Ags appear to be confined to an intraphagosomal processing
      pathway that requires higher concentrations of Ags, suggesting that these
      parasites may have evolved strategies to impair the efficient endoplasmic
      reticulum-based, TAP-dependent cross-presentation pathway to avoid or delay CD8+
      T cell priming.

PMID- 16951312
TI  - Thrombospondin/CD47 interaction: a pathway to generate regulatory T cells from
      human CD4+ CD25- T cells in response to inflammation.
AB  - Thymus-derived CD4+ CD25+ T regulatory cells (Tregs) are essential for the
      maintenance of self-tolerance. What critical factors and conditions are required
      for the extra-thymic development of Tregs remains an important question. In this
      study, we show that the anti-inflammatory extracellular matrix protein,
      thrombospondin-1, promoted the generation of human peripheral regulatory T cells
      through the ligation of one of its receptor, CD47. CD47 stimulation by mAb or a
      thrombospondin-1 peptide induced naive or memory CD4+ CD25- T cells to become
      suppressive. The latter expressed increased amounts of CTLA-4, OX40, GITR, and
      Foxp3 and inhibited autologous Th0, Th1, and Th2 cells. Their regulatory activity
      was contact dependent, TGF-beta independent, and partially circumvented by IL-2.
      This previously unknown mechanism to induce human peripheral Tregs in response to
      inflammation may participate to the limitation of collateral damage induced by
      exacerbated responses to self or foreign Ags and thus be relevant for therapeutic
      intervention in autoimmune diseases and transplantation.

PMID- 16951313
TI  - IFN-beta inhibits T cell activation capacity of central nervous system APCs.
AB  - We have previously investigated the physiological effects of IFN-beta on chronic
      CNS inflammation and shown that IFN-beta(-/-) mice develop a more severe
      experimental autoimmune encephalomyelitis than their IFN-beta(+/-) littermates.
      This result was shown to be associated with a higher activation state of the
      glial cells and a higher T cell cytokine production in the CNS. Because this
      state suggested a down-regulatory effect of IFN-beta on CNS-specific APCs, these
      results were investigated further. We report that IFN-beta pretreatment of
      astrocytes and microglia (glial cells) indeed down-modulate their capacity to
      activate autoreactive Th1 cells. First, we investigated the intrinsic ability of
      glial cells as APCs and report that glial cells prevent autoreactive Th1 cells
      expansion while maintaining Ag-specific T cell effector functions. However, when
      the glial cells are treated with IFN-beta before coculture with T cells, the
      effector functions of T cells are impaired as IFN-gamma, TNF-alpha, and NO
      productions are decreased. Induction of the T cell activation marker, CD25 is
      also reduced. This suppression of T cell response is cell-cell dependent, but it
      is not dependent on a decrease in glial expression of MHC class II or
      costimulatory molecules. We propose that IFN-beta might exert its beneficial
      effects mainly by reducing the Ag-presenting capacity of CNS-specific APCs, which
      in turn inhibits the effector functions of encephalitogenic T cells. This affect
      is of importance because activation of encephalitogenic T cells within the CNS is
      a prerequisite for the development of a chronic progressive CNS inflammation.

PMID- 16951314
TI  - IFN-gamma and T-bet expression in human dendritic cells from normal donors and
      cancer patients is controlled through mechanisms involving ERK-1/2-dependent and
      IL-12-independent pathways.
AB  - Dendritic cells (DC) play a major role in priming naive T cells and modulating
      the immune response. We have previously reported that bryostatin-1, a potent
      immune modulator with antitumor activity, activates monocytes and lymphocytes to
      produce cytokines. Studies have shown that tumor-bearing hosts have a Th1/Th2
      cytokine pattern that is associated with decreased production of IFN-gamma. We
      investigated the expression of IFN-gamma in bryostatin-1-treated human DC.
      Bryostatin-1 induced both IFN-gamma and T-bet mRNA expression in a dose- and time
      dependent manner. As little as 1 ng/ml bryostatin-1 induced IFN-gamma and T-bet
      transcripts within 3 h and protein at 12 h. Treatment of DC with cycloheximide
      revealed that bryostatin-1-induced T-bet expression requires de novo protein
      synthesis, but bryostatin-1-induced IFN-gamma expression is independent of
      protein synthesis. Furthermore, dexamethasone inhibits bryostatin-1-induced IFN
      gamma mRNA expression but increases bryostatin-1-induced T-bet mRNA expression.
      Experiments with ERK-1/2 inhibitors demonstrated that bryostatin-1 induction of
      IFN- gamma and T-bet was ERK-dependent and IL-12-independent. Similar results
      were obtained from both normal donors and cancer patients. In summary, our
      results suggest that bryostatin-1-induced IFN-gamma expression is T-bet
      independent. They also suggest for the first time that IFN- gamma and T-bet can
      be induced in human DC through an ERK-dependent pathway. Bryostatin-1-induced IFN
      gamma may play a crucial role in the initiation of the immune response, before
      specific recognition by T cells that could be beneficial in the treatment of
      cancer.

PMID- 16951315
TI  - Induction of efficient antitumor immunity using dendritic cells activated by
      recombinant Sendai virus and its modulation by exogenous IFN-beta gene.
AB  - Dendritic cell (DC)-based cancer immunotherapy has been paid much attention as a
      new and cancer cell-specific therapeutic in the last decade; however, little
      clinical outcome has been reported. Current limitations of DC-based cancer
      immunotherapy include sparse information about which DC phenotype should be
      administered. We here report a unique, representative, and powerful method to
      activate DCs, namely recombinant Sendai virus-modified DCs (SeV/DC), for cancer
      immunotherapy. In vitro treatment of SeV without any bioactive gene solely led
      DCs to a mature phenotype. Even though the expression of surface markers for DC
      activation ex vivo did not always reach the level attained by an optimized amount
      of LPS, superior antitumor effects to B16F1 melanoma, namely tumor elimination
      and survival, were obtained with use of SeV-GFP/DC as compared with those seen
      with LPS/DC in vivo, and the effect was enhanced by SeV/DC-expressing IFN-beta
      (SeV-murine IFN-beta (mIFN-beta)/DC). In case of the treatment of an established
      tumor of B16F10 (7-9 mm in diameter), a highly malignant subline of B16 melanoma,
      SeV-modified DCs (both SeV-GFP/DC and SeV-mIFN-beta/DC), but not immature DC and
      LPS/DC, dramatically improved the survival of animals. Furthermore, SeV-mIFN
      beta/DC but not other DCs could lead B16F10 tumor to the dormancy, associated
      with strongly enhanced CD8+ CTL responses. These results indicate that rSeV is a
      new and powerful tool as an immune booster for DC-based cancer immunotherapy that
      can be significantly modified by IFN-beta, and SeV/DC, therefore, warrants
      further investigation as a promising alternative for cancer immunotherapy.

PMID- 16951316
TI  - Dendritic cell modulation by mast cells controls the Th1/Th2 balance in
      responding T cells.
AB  - The cytokines secreted by pathogen-activated human dendritic cells (DC) are
      strongly regulated in vitro by histamine, a major component of mast cell
      granules, ultimately modulating the capacity of the DC to polarize naive T cells.
      Because DC and mast cells are located in close proximity in peripheral
      compartments, we hypothesized that mast cell products would influence the
      maturation of DC and hence the Th balance of an immune response in vivo. In this
      study, we show that specific mast cell degranulation stimuli, given s.c. in mice
      with Ag and adjuvant, produce effector T cells that proliferate to Ag but secrete
      dramatically reduced levels of IFN-gamma and increased amounts of IL-4 compared
      with control T cells primed in the absence of a mast cell stimulus. Immunization
      with Ag and adjuvant in the presence of a degranulation stimulus also resulted in
      the accumulation of DC in the draining lymph nodes that had reduced capacity to
      induce Ag-specific Th1 cells, in comparison with DC from mice lacking a
      degranulation stimulus. Therefore, by acting upon DC at sites of inflammation,
      mast cells play a critical role in determining the polarity of Ag-specific T cell
      responses in vivo.

PMID- 16951317
TI  - Dendritic cell surface calreticulin is a receptor for NY-ESO-1: direct
      interactions between tumor-associated antigen and the innate immune system.
AB  - How the immune system recognizes endogenously arising tumors and elicits adaptive
      immune responses against nonmutated tumor-associated Ags is poorly understood. In
      search of intrinsic factors contributing to the immunogenicity of the tumor
      associated Ag NY-ESO-1, we found that the NY-ESO-1 protein binds to the surface
      of immature dendritic cells (DC), macrophages, and monocytes, but not to that of
      B cells or T cells. Using immunoprecipitation coupled with tandem mass
      spectrometry, we isolated DC surface calreticulin as the receptor for NY-ESO-1.
      Calreticulin Abs blocked NY-ESO-1 binding on immature DC and its cross
      presentation to CD8+ T cells in vitro. Calreticulin/NY-ESO-1 interactions provide
      a direct link between NY-ESO-1, the innate immune system, and, potentially, the
      adaptive immune response against NY-ESO-1.

PMID- 16951318
TI  - CD94/NKG2A inhibits NK cell activation by disrupting the actin network at the
      immunological synapse.
AB  - An adequate immune response is the result of the fine balance between activation
      and inhibitory signals. The exact means by which inhibitory signals obviate
      activation signals in immune cells are not totally elucidated. Human CD94/NKG2A
      is an ITIM-containing inhibitory receptor expressed by NK cells and some CD8+ T
      cells that recognize HLA-E. We show that the engagement of this receptor prevents
      NK cell activation by disruption of the actin network and exclusion of lipid
      rafts at the point of contact with its ligand (inhibitory NK cell immunological
      synapse, iNKIS). CD94/NKG2A engagement leads to recruitment and activation of src
      homology 2 domain-bearing tyrosine phosphatase 1. This likely explains the
      observed dephosphorylation of guanine nucleotide exchange factor and regulator of
      actin, Vav1, as well as ezrin-radixin-moesin proteins that connect actin
      filaments to membrane structures. In contrast, NK cell activation by NKG2D
      induced Vav1 and ezrin-radixin-moesin phosphorylation. Thus, CD94/NKG2A prevents
      actin-dependent recruitment of raft-associated activation receptors complexes to
      the activating synapse. This was further substantiated by showing that inhibition
      of actin polymerization abolished lipid rafts exclusion at the iNKIS, whereas
      cholesterol depletion had no effect on actin disruption at the iNKIS. These data
      indicate that the lipid rafts exclusion at the iNKIS is an active process which
      requires an intact cytoskeleton to maintain lipid rafts outside the inhibitory
      synapse. The net effect is to maintain an inhibitory state in the proximity of
      the iNKIS, while allowing the formation of activation synapse at distal points
      within the same NK cell.

PMID- 16951319
TI  - The extracellular membrane-proximal domain of human membrane IgE controls
      apoptotic signaling of the B cell receptor in the mature B cell line A20.
AB  - Ag engagement of BCR in mature B cells can deliver specific signals, which decide
      cell survival or cell death. Circulating membrane IgE+ (mIgE+) cells are found in
      extremely low numbers. We hypothesized that engagement of an epsilonBCR in a
      mature isotype-switched B cell could induce apoptosis. We studied the role of the
      extracellular membrane-proximal domain (EMPD) of human mIgE upon BCR engagement
      with anti-Id Abs. Using mutants lacking the EMPD, we show that this domain is
      involved in controlling Ca2+ mobilization in immunoreceptors of both gamma and
      epsilon isotypes, as well as apoptosis in signaling originated only from the
      epsilonBCR. We mapped to the epsilonCH4 ectodomain the region responsible for
      apoptosis in EMPD-deleted receptors. Ca2+ mobilization was not related to
      apoptotic signaling. This apoptotic pathway was caspase independent, involved
      ERK1/2 phosphorylation and was partially rescued by CD40 costimulation. We
      therefore conclude that the EMPD of human mIgE is a key control element of
      apoptotic signaling delivered through engagement of epsilonBCR within the context
      of a mature B cell.

PMID- 16951320
TI  - B7H1-Ig fusion protein activates the CD4+ IFN-gamma receptor+ type 1 T regulatory
      subset through IFN-gamma-secreting Th1 cells.
AB  - It has been demonstrated in our previous work that, in the human skin-grafting
      model, the expression of costimulatory molecule B7H1 (PD-L1) by keratinocytes
      plays an essential role in inducing local tolerance via activation of IL-10
      secreting T cells. This study further analyzes the role of B7H1 in
      differentiation of type 1 T regulatory (Tr1) cells and explores underlying
      mechanisms. Mouse fusion protein B7H1-Ig is used, together with immobilized anti
      CD3 mAb, to costimulate the purified naive CD4+ T cells. B7H1-Ig-treated CD4+ T
      cells were found to activate a characteristic Tr1 population possessing a CD4+
      CD25- Foxp3- CD45RBlow phenotype. These regulatory T cells strongly inhibited the
      Th1-dominated MLR by secretion of IL-10 and TGF-beta. Moreover, B7H1-treated Tr1
      cells also resulted in suppressed clinical scores and demyelination when
      adoptively transferred into mice with experimental allergic encephalomyelitis.
      Furthermore, analysis of the cytokine profile indicated that there were two
      differential reaction patterns during the B7H1-Ig-induced Tr1 development. These
      two patterns were characterized by activation of IFN-gammaR+ IL-10R- Th1 and IFN
      gammaR+ IL-10R+ Tr1 cells, respectively. Secretion of IFN-gamma by Th1 and the
      expression of IFN-gammaR on Tr1 were critical for further Tr1 differentiation, as
      demonstrated by mAb blocking and by analysis in IFN-gamma(-/-) mice. In
      conclusion, B7H1 is capable of inducing Tr1 differentiation from naive CD4+ T
      cells by coactivation in an IFN-gamma- or Th1-dependent manner. Our study may
      shed some light upon the clinical usage of B7H1 as a therapeutic reagent for
      induction of tolerance.

PMID- 16951321
TI  - Liver sinusoidal endothelial cells that endocytose allogeneic cells suppress T
      cells with indirect allospecificity.
AB  - A portal venous injection of allogeneic donor cells is known to prolong the
      survival of subsequently transplanted allografts. In this study, we investigated
      the role of liver sinusoidal endothelial cells (LSECs) in immunosuppressive
      effects induced by a portal injection of allogeneic cells on T cells with
      indirect allospecificity. To eliminate the direct CD4+ T cell response, C57BL/6
      (B6) MHC class II-deficient C2tatm1Ccum (C2D) mice were used as donors. After
      portal injection of irradiated B6 C2D splenocytes into BALB/c mice, the host
      LSECs that endocytosed the irradiated allogeneic splenocytes showed enhanced
      expression of MHC class II molecules, CD80, and Fas ligand (FasL). Due to
      transmigration across the LSECs from BALB/c mice treated with a portal injection
      of B6 C2D splenocytes, the naive BALB/c CD4+ T cells lost their responsiveness to
      stimulus of BALB/c splenic APCs that endocytose donor-type B6 C2D alloantigens,
      while maintaining a normal response to stimulus of BALB/c splenic APCs that
      endocytose third-party C3H alloantigens. Similar results were not observed for
      naive BALB/c CD4+ T cells that transmigrated across the LSECs from BALB/c FasL
      deficient mice treated with a portal injection of B6 C2D splenocytes. Adaptive
      transfer of BALB/c LSECs that had endocytosed B6 C2D splenocytes into BALB/c mice
      via the portal vein prolonged the survival of subsequently transplanted B6 C2D
      hearts; however, a similar effect was not observed for BALB/c FasL-deficient
      LSECs. These findings indicate that LSECs that had endocytosed allogeneic
      splenocytes have immunosuppressive effects on T cells with indirect
      allospecificity, at least partially via the Fas/FasL pathway.

PMID- 16951322
TI  - T cell-dependent activation of dendritic cells requires IL-12 and IFN-gamma
      signaling in T cells.
AB  - Patients presenting with genetic deficiencies in IFNGR1, IFNGR2, IL-12B, and IL
      12RB1 display increased susceptibility to mycobacterial infections. We analyzed
      in this group of patients the cross-talk between human CD4+ T lymphocytes and
      dendritic cells (DCs) that leads to maturation of DC into producers of bioactive
      IL-12 and to activation of T cells into IFN-gamma producers. We found that this
      cross-talk is defective in all patients from this group. Unraveling the
      mechanisms underlying this deficiency, we showed that IL-12 signaling in T cells
      is required to induce expression of costimulatory molecules and secretion of IL
      12 by DCs and that IFNGR expression is required on both DCs and CD4+ T cells to
      induce IL-12 secretion by DCs. These data suggest that CD4+ T cell-mediated
      activation of DCs plays a critical role in the defense against mycobacterial
      infections in humans.

PMID- 16951323
TI  - Hydrodynamic-based delivery of an interleukin-22-Ig fusion gene ameliorates
      experimental autoimmune myocarditis in rats.
AB  - IL-22 is one of several cytokines with limited homology to IL-10. However, the
      biological activities of IL-22 are mostly unknown. The purpose of this study was
      to evaluate the effect of IL-22 on rat experimental autoimmune myocarditis (EAM)
      and elucidate an aspect of the biological activities of IL-22. Rats were
      immunized on day 0; IL-22-Ig-treated rats were injected with pCAGGS-IL-22-Ig and
      control rats with pCAGGS-Ig using hydrodynamics-based gene delivery on day 1 or
      day 6. IL-22-Ig gene therapy administered on day 1 or day 6 after immunization
      was effective in controlling EAM as monitored by the heart weight to body weight
      ratio, and the myocarditis area in rats was sacrificed on day 17. Examination of
      the expression of IL-22-related genes in purified cells from EAM hearts suggested
      that IL-22-Ig acting target cells were noncardiomyocytic (NC) noninflammatory
      cells such as fibroblasts, smooth muscle cells, and endothelial cells. Therefore,
      we examined the effect of rIL-22 or serum containing IL-22-Ig on the expression
      of immune-relevant genes in IL-1-stimulated NC cells cultured from EAM hearts.
      Results showed that the expression of immunologic molecules (PGE synthase,
      cyclooxygenase-2, MIP-2, MCP-1, IL-6, and cytokine-induced neutrophil
      chemoattractant-2) in IL-1-stimulated NC cells was significantly decreased by rIL
      22 or serum containing IL-22-Ig. EAM was suppressed by hydrodynamics-based
      delivery of plasmid DNA encoding IL-22-Ig, and the reason for this effectiveness
      may be that IL-22 suppressed gene expression of PG synthases, IL-6, and
      chemokines in activated NC noninflammatory cells.

PMID- 16951324
TI  - Different neurotropic pathogens elicit neurotoxic CCR9- or neurosupportive CXCR3
      expressing microglia.
AB  - What mechanism that determines microglia accomplishing destructive or
      constructive role in CNS remains nebulous. We report here that intracranial
      priming and rechallenging with Toxoplasma gondii in mice elicit neurotoxic CCR9+
      Irg1+ (immunoresponsive gene 1) microglia, which render resistance to apoptosis
      and produce a high level of TNF-alpha; priming and rechallenging with lymphocytic
      choriomeningitis virus elicit neurosupportive CXCR3+ Irg1- microglia, which are
      sensitive to apoptosis and produce a high level of IL-10 and TGF-beta.
      Administration of CCR9 and/or Irg1 small interfering RNA alters the frequency and
      functional profiles of neurotoxic CCR9+ Irg1+ and neurosupportive CXCR3+ Irg1-
      microglia in vivo. Moreover, by using a series of different neurotropic
      pathogens, including intracellular parasites, chronic virus, bacteria, toxic
      substances, and CNS injury to intracranially prime and subsequent rechallenge
      mice, the bi-directional elicitation of microglia has been confirmed as
      neurotoxic CCR9+ Irg1+ and neurosupportive CXCR3+ Irg1- cells in these mouse
      models. These data suggest that there exist two different types of microglia,
      providing with a novel insight into microglial involvement in neurodegenerative
      and neuroinflammatory pathogenesis such as Alzheimer's disease and AIDS dementia.

PMID- 16951325
TI  - Mechanisms regulating the proliferative potential of human CD8+ T lymphocytes
      overexpressing telomerase.
AB  - In human somatic cells, including T lymphocytes, telomeres progressively shorten
      with each cell division, eventually leading to a state of cellular senescence.
      Ectopic expression of telomerase results in the extension of their replicative
      life spans without inducing changes associated with transformation. However, it
      is yet unknown whether somatic cells that overexpress telomerase are
      physiologically indistinguishable from normal cells. Using CD8+ T lymphocyte
      clones overexpressing telomerase, we investigated the molecular mechanisms that
      regulate T cell proliferation. In this study, we show that early passage T cell
      clones transduced or not with human telomerase reverse transcriptase displayed
      identical growth rates upon mitogenic stimulation and no marked global changes in
      gene expression. Surprisingly, reduced proliferative responses were observed in
      human telomerase reverse transcriptase-transduced cells with extended life spans.
      These cells, despite maintaining high expression levels of genes involved in the
      cell cycle progression, also showed increased expression in several genes found
      in common with normal aging T lymphocytes. Strikingly, late passage T cells
      overexpressing telomerase accumulated the cyclin-dependent inhibitors p16Ink4a
      and p21Cip1 that have largely been associated with in vitro growth arrest. We
      conclude that alternative growth arrest mechanisms such as those mediated by
      p16Ink4a and p21Cip1 still remained intact and regulated the growth potential of
      cells independently of their telomere status.

PMID- 16951326
TI  - CD4 expression on activated NK cells: ligation of CD4 induces cytokine expression
      and cell migration.
AB  - NK cells play an important role in the innate immune response. We have isolated
      NK cells from human lymphoid tissues and found that these cells express the CD4
      molecule on their surface at levels higher than those found on peripheral blood
      NK cells. To study the functional role of the CD4 molecule on NK cells, we
      developed an in vitro system by which we are able to obtain robust CD4 expression
      on NK cells derived from blood. CD4+ NK cells efficiently mediate NK cell
      cytotoxicity, and CD4 expression does not appear to alter lytic function. CD4+ NK
      cells are more likely to produce the cytokines gamma-IFN and TNF-alpha than are
      CD4- NK cells. Ligation of CD4 further increases the number of NK cells producing
      these cytokines. NK cells expressing CD4 are also capable of migrating toward the
      CD4-specific chemotactic factor IL-16, providing another function for the CD4
      molecule on NK cells. Thus, the CD4 molecule is present and functional on NK
      cells and plays a role in innate immune responses as a chemotactic receptor and
      by increasing cytokine production, in addition to its well-described function on
      T cells as a coreceptor for Ag responsive cell activation.

PMID- 16951327
TI  - The major glycoprotein allergen from Arachis hypogaea, Ara h 1, is a ligand of
      dendritic cell-specific ICAM-grabbing nonintegrin and acts as a Th2 adjuvant in
      vitro.
AB  - Nonmammalian glycan structures from helminths act as Th2 adjuvants. Some of these
      structures are also common on plant glycoproteins. We hypothesized that glycan
      structures present on peanut glycoallergens act as Th2 adjuvants. Peanut Ag
      (PNAg), but not deglycosylated PNAg, activated monocyte-derived dendritic cells
      (MDDCs) as measured by MHC/costimulatory molecule up-regulation, and by their
      ability to drive T cell proliferation. Furthermore, PNAg-activated MDDCs induced
      2- to 3-fold more IL-4- and IL-13-secreting Th2 cells than immature or TNF/IL-1
      activated MDDCs when cultured with naive CD4+ T cells. Human MDDCs rapidly
      internalized Ag in a calcium- and glycan-dependent manner consistent with
      recognition by C-type lectin. Dendritic cell (DC)-specific ICAM-grabbing
      nonintegrin (DC-SIGN) (CD209) was shown to recognize PNAg by enhanced uptake in
      transfected cell lines. To identify the DC-SIGN ligand from unfractionated PNAg,
      we expressed the extracellular portion of DC-SIGN as an Fc-fusion protein and
      used it to immunoprecipitate PNAg. A single glycoprotein was pulled down in a
      calcium-dependent manner, and its identity as Ara h 1 was proven by
      immunolabeling and mass spectrometry. Purified Ara h 1 was found to be sufficient
      for the induction of MDDCs that prime Th2-skewed T cell responses. Both PNAg and
      purified Ara h 1 induced Erk 1/2 phosphorylation of MDDCs, consistent with
      previous reports on the effect of Th2 adjuvants on DCs.

PMID- 16951328
TI  - Invariant NKT cells rapidly activated via immunization with diverse contact
      antigens collaborate in vitro with B-1 cells to initiate contact sensitivity.
AB  - In cutaneous contact sensitivity there is an early elicited innate cascade of
      complement, mast cells, and platelets activated via IgM Abs. This response is
      required to initiate the elicitation of acquired classical contact sensitivity by
      leading to local recruitment of effector T cells. We recently performed in vivo
      experiments showing that collaboration is required between innate-like invariant
      Valpha14+ NKT cells (iNKT) and the innate-like B-1 B cell subset to induce this
      initiation process. Contact sensitization triggers iNKT cells to produce IL-4 to
      coactivate the B-1 cells along with specific Ag for production of the initiating
      IgM Abs. We now describe in vitro collaboration of iNKT and B-1 cells. Normal
      peritoneal B-1 cells, incubated in vitro with soluble Ag, and with 1-h in vivo
      immune iNKT cells producing IL-4, are activated to mediate the contact
      sensitivity-initiation cascade. The three components of this process can be
      activated by different Ag. Thus, 1-h iNKT cell activation, B-1 cell stimulation,
      and generation of immune effector T cells can be induced by sensitization with
      three different Ag to respectively generate IL-4 and Ag-specific IgM Abs, to
      recruit the Ag-specific effector T cells. These findings have relevance to
      allergic and autoimmune diseases in which infections can trigger exacerbation of
      T cell responses to allergens or to autoantigens.

PMID- 16951329
TI  - Protection from type 1 diabetes by invariant NK T cells requires the activity of
      CD4+CD25+ regulatory T cells.
AB  - Invariant NK T (iNKT) cells regulate immune responses, express NK cell markers
      and an invariant TCR, and recognize lipid Ags in a CD1d-restricted manner.
      Previously, we reported that activation of iNKT cells by alpha-galactosylceramide
      (alpha-GalCer) protects against type 1 diabetes (T1D) in NOD mice via an IL-4
      dependent mechanism. To further investigate how iNKT cells protect from T1D, we
      analyzed whether iNKT cells require the presence of another subset(s) of
      regulatory T cells (Treg), such as CD4+ CD25+ Treg, for this protection. We found
      that CD4+ CD25+ T cells from NOD.CD1d(-/-) mice deficient in iNKT cell function
      similarly in vitro to CD4+ CD25+ T cells from wild-type NOD mice and suppress the
      proliferation of NOD T responder cells upon alpha-GalCer stimulation. Cotransfer
      of NOD diabetogenic T cells with CD4+ CD25+ Tregs from NOD mice pretreated with
      alpha-GalCer demonstrated that activated iNKT cells do not influence the ability
      of T(regs) to inhibit the transfer of T1D. In contrast, protection from T1D
      mediated by transfer of activated iNKT cells requires the activity of CD4+ CD25+
      T cells, because splenocytes pretreated with alpha-GalCer and then inactivated by
      anti-CD25 of CD25+ cells did not protect from T1D. Similarly, mice inactivated of
      CD4+ CD25+ T cells before alpha-GalCer treatment were also not protected from
      T1D. Our data suggest that CD4+ CD25+ T cells retain their function during iNKT
      cell activation, and that the activity of CD4+ CD25+ Tregs is required for iNKT
      cells to transfer protection from T1D.

PMID- 16951330
TI  - Modelling two possible mechanisms for the regulation of the germinal center
      dynamics.
AB  - Research on the germinal center has tried to unravel the mechanisms that control
      its dynamics. In this study we focus on the termination of the germinal center
      reaction, which is still an open problem. We propose two hypothetical biological
      mechanisms that may be responsible for the control of germinal center dynamics
      and analyze them through mathematical models. The first one is based on the
      differentiation of follicular dendritic cells and/or T cells. Interaction of
      these cells in the differentiated state with germinal center B cells would
      promote B cell differentiation into memory B cells and Ab-forming cells, ending
      the germinal center reaction. The second mechanism applies only to a scenario
      without recycling and consists of the decay of a hypothetical proliferation
      signal for centroblasts that limits the number of cell divisions. Each of the
      models makes predictions that can be experimentally tested.

PMID- 16951331
TI  - Notch1 and IL-7 receptor interplay maintains proliferation of human thymic
      progenitors while suppressing non-T cell fates.
AB  - Notch signaling is critical for T cell development of multipotent hemopoietic
      progenitors. Yet, how Notch regulates T cell fate specification during early
      thymopoiesis remains unclear. In this study, we have identified an early subset
      of CD34high c-kit+ flt3+ IL-7Ralpha+ cells in the human postnatal thymus, which
      includes primitive progenitors with combined lymphomyeloid potential. To assess
      the impact of Notch signaling in early T cell development, we expressed
      constitutively active Notch1 in such thymic lymphomyeloid precursors (TLMPs), or
      triggered their endogenous Notch pathway in the OP9-Delta-like1 stroma coculture.
      Our results show that proliferation vs differentiation is a critical decision
      influenced by Notch at the TLMP stage. We found that Notch signaling plays a
      prominent role in inhibiting non-T cell differentiation (i.e., macrophages,
      dendritic cells, and NK cells) of TLMPs, while sustaining the proliferation of
      undifferentiated thymocytes with T cell potential in response to unique IL-7
      signals. However, Notch activation is not sufficient for inducing T-lineage
      progression of proliferating progenitors. Rather, stroma-derived signals are
      concurrently required. Moreover, while ectopic IL-7R expression cannot replace
      Notch for the maintenance and expansion of undifferentiated thymocytes, Notch
      signals sustain IL-7R expression in proliferating thymocytes and induce IL-7R up
      regulation in a T cell line. Thus, IL-7R and Notch pathways cooperate to
      synchronize cell proliferation and suppression of non-T lineage choices in
      primitive intrathymic progenitors, which will be allowed to progress along the T
      cell pathway only upon interaction with an inductive stromal microenvironment.
      These data provide insight into a mechanism of Notch-regulated amplification of
      the intrathymic pool of early human T cell progenitors.

PMID- 16951332
TI  - IL-21 inhibits IFN-gamma production in developing Th1 cells through the
      repression of Eomesodermin expression.
AB  - Exposure of naive Th cell precursors (Thp) to IL-21 inhibits IFN-gamma production
      from developing Th1 cells. The inhibition of IFN-gamma seen in IL-21-treated Thp
      cells is specific as the expression of other Th1 cytokines is unaffected.
      Recently, it has been reported that Eomesodermin (Eomes), a member of the T-box
      gene family, is expressed in developing CD8+ T cells and plays an important role
      in regulating IFN-gamma production and cytolytic effector function. In this
      study, we show that Eomes mRNA and protein are also expressed in developing Th1
      cells, and exposure of naive Thp cells to IL-21 results in a decrease in Eomes
      expression. Moreover, the repression of Eomes expression by IL-21 is not due to
      an indirect effect of IL-21 on the expression of IFN-gamma or STAT4 and is
      independent of STAT1 and T-bet expression. Finally, we show that ectopic
      expression of Eomes prevents the inhibition of IFN-gamma production from IL-21
      treated Thp cells. Taken together, these results demonstrate that Eomes plays a
      role in regulating IFN-gamma production in CD4+ T cells and IL-21 inhibits IFN
      gamma production in developing Th1 cells through the repression of Eomes
      expression.

PMID- 16951333
TI  - A new memory CD27-IgG+ B cell population in peripheral blood expressing VH genes
      with low frequency of somatic mutation.
AB  - In humans, up to 40% of peripheral B cells express CD27 and have hypermutated
      variable regions in their Ig genes. The CD27+ B cells are considered to be
      derived from germinal center following specific antigenic stimulation. Actually,
      somatic hypermutation in Ig genes and CD27 expression are hallmarks of memory B
      cells. However, the blood IgM+ IgD+ CD27+ B cells were recently associated to
      splenic marginal zone B cells and proposed to be a subset distinct from germinal
      center-derived memory B cells showing premutated Igs. The results presented
      herein further weaken this bona fide association because B cells expressing
      surface IgG, but not CD27, were found in human blood. Representing 1-4% of all
      peripheral B cells and approximately 25% of the IgG+ blood B cells, this
      population expressed mutated IgG genes showing antigenic selection
      characteristics but with lower mutation frequencies than that of CD27+ IgG+ B
      cells. However, their morphology and phenotype were similar to that of CD27+ IgG+
      cells. Interestingly, the proportion of IgG2 over IgG3 transcripts was opposite
      in CD27- IgG+ and CD27+ IgG+ cells, suggesting distinct functions or origins.
      Overall, these findings extend the memory B cell reservoir beyond the CD27+
      compartment and could provide further insights into B cell disorders of unknown
      etiology.

PMID- 16951334
TI  - Peroxisome proliferator-activated receptor gamma promotes lymphocyte survival
      through its actions on cellular metabolic activities.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a metabolic
      regulator that plays an important role in sensitizing tissues to the action of
      insulin and in normalizing serum glucose and free fatty acids in type 2 diabetic
      patients. The receptor has also been implicated in the modulation of inflammatory
      responses, and ligands of PPARgamma have been found to induce apoptosis in
      lymphocytes. However, apoptosis induction may not depend on the receptor, because
      high doses of PPARgamma agonists are required for this process. Using cells
      containing or lacking PPARgamma, we reported previously that PPARgamma attenuates
      apoptosis induced by cytokine withdrawal in a murine lymphocytic cell line via a
      receptor-dependent mechanism. PPARgamma exerts this effect by enhancing the
      ability of cells to maintain their mitochondrial membrane potential during
      cytokine deprivation. In this report, we demonstrate that activation of PPARgamma
      also protects cells from serum starvation-induced apoptosis in human T lymphoma
      cell lines. Furthermore, we show that the survival effect of PPARgamma is
      mediated through its actions on cellular metabolic activities. In cytokine
      deprived cells, PPARgamma attenuates the decline in ATP level and suppresses
      accumulation of reactive oxygen species (ROS). Moreover, PPARgamma regulates ROS
      through its coordinated transcriptional control of proteins and enzymes involved
      in ROS scavenging, including uncoupling protein 2, catalase, and copper zinc
      superoxide dismutase. Our studies identify cell survival promotion as a novel
      activity of PPARgamma and suggest that PPARgamma may modulate cytokine withdrawal
      induced activated T cell death.

PMID- 16951335
TI  - A role for intercellular antigen transfer in the recognition of EBV-transformed B
      cell lines by EBV nuclear antigen-specific CD4+ T cells.
AB  - The CD4+ T cell response to EBV may have an important role in controlling virus
      driven B lymphoproliferation because CD4+ T cell clones to a subset of EBV
      nuclear Ag (EBNA) epitopes can directly recognize virus-transformed
      lymphoblastoid cell lines (LCLs) in vitro and inhibit their growth. In this
      study, we used a panel of EBNA1, 2, 3A, and 3C-specific CD4+ T cell clones to
      study the route whereby endogenously expressed EBNAs access the HLA class II
      presentation pathway. Two sets of results spoke against a direct route of
      intracellular access. First, none of the clones recognized cognate Ag
      overexpressed in cells from vaccinia vectors but did recognize Ag fused to an
      endo/lysosomal targeting sequence. Second, focusing on clones with the strongest
      LCL recognition that were specific for EBNA2- and EBNA3C-derived epitopes LCL
      recognition was unaffected by inhibiting autophagy, a postulated route for
      intracellular Ag delivery into the HLA class II pathway in LCL cells.
      Subsequently, using these same epitope-specific clones, we found that Ag-negative
      cells with the appropriate HLA-restricting allele could be efficiently sensitized
      to CD4+ T cell recognition by cocultivation with Ag-positive donor lines or by
      exposure to donor line-conditioned culture medium. Sensitization was mediated by
      a high m.w. antigenic species and required active Ag processing by recipient
      cells. We infer that intercellular Ag transfer plays a major role in the
      presentation of EBNA-derived CD4 epitopes by latently infected target cells.

PMID- 16951336
TI  - Exosomes from bone marrow dendritic cells pulsed with diphtheria toxoid
      preferentially induce type 1 antigen-specific IgG responses in naive recipients
      in the absence of free antigen.
AB  - Exosomes derived from dendritic cells (DC) activate T cells in vivo, but whether
      exosomes are able to induce and/or modulate humoral immune responses is still
      unknown. We show that murine bone marrow DC pulsed in vitro with an intact
      protein (diphtheria toxoid (DT)) produce exosomes that induce, in the absence of
      free protein, in vivo Ig responses specific for DT in naive recipients.
      Furthermore, these exosomes stimulate secondary IgG anti-DT responses in mice
      primed with intact DT. Exosomes from mature, relative to immature, DC were more
      effective at inducing primary, although not secondary, IgG anti-DT responses.
      Whereas intact DT preferentially induced a type 2 (IgG1) anti-DT response,
      exosomes from DT-pulsed bone marrow DC favored induction of type 1 (IgG2b and
      IgG2a) DT-specific IgG. These results are the first to demonstrate the ability of
      exosomes derived from Ag-pulsed DC to induce and modulate Ag-specific humoral
      immunity in vivo.

PMID- 16951337
TI  - IL-12 instructs skin homing of human Th2 cells.
AB  - Distinct pattern of homing receptors determines the tissue preference for T cells
      to exert their effector functions. This homing competence is mostly determined
      early during T cell activation of naive T cells. In contrast, mechanisms
      governing the acquisition of particular homing receptors by T cells of the memory
      phenotype remain enigmatic. Th2 cell-mediated allergic diseases tend to flare
      during infections despite that these infections prime APCs to produce the
      prototypic Th1 cell-differentiating cytokine IL-12. In this study, we investigate
      the effect of IL-12 on the regulation of cutaneous lymphocyte Ag (CLA) on
      differentiated Th2 cells and consequences of this expression for allergic
      inflammation. Upon activation with IL-12, CLA- Th2 cells rapidly up-regulated IL
      12Rbeta2 chain, alpha(1-3)-fucosyltransferase VII, and CLA molecules. IL-12
      mediated CLA expression on Th2 cells was functional because it mediated rolling
      of these Th2 cells on E-selectin in vitro and migration into human skin grafts in
      SCID mice. CLA induction occurred immediately after exposure to IL-12 and was
      independent of IFN-gamma expression. In accordance, the transcription factor
      mediating IFN-gamma expression, T-bet, does not directly affect CLA expression.
      However, CLA expression was further enhanced after IL-12 treatment of T-bet+ 
      transfected Th2 cells in agreement with an increased IL-12 responsiveness of
      these cells caused by T-bet. The finding that IL-12 conferred skin-homing
      potential to already differentiated Th2 cells before inducing a switch in their
      cytokine production profile may explain the observed exacerbation of allergic
      skin diseases following bacterial infections.

PMID- 16951338
TI  - Monocyte 15-lipoxygenase expression is regulated by a novel cytosolic signaling
      complex with protein kinase C delta and tyrosine-phosphorylated Stat3.
AB  - Our previous studies demonstrated that the IL-13-induced 15-lipoxygenase
      expression in primary human monocytes is regulated by the activation of both
      Stat1 and Stat3 and by protein kinase C (PKC)delta. IL-13 stimulated the
      phosphorylation of Stat3 on both Tyr705 and Ser727. In this study we show that IL
      13 induces the association of PKCdelta with Stat3, not with Stat1, and is
      required for Stat3 Ser727 phosphorylation. We found a novel IL-13-dependent
      cytosolic signaling complex of PKCdelta and tyrosine-phosphorylated Stat3. A
      tyrosine kinase inhibitor blocked PKCdelta association with Stat3 as well as
      Stat3 Ser727 phosphorylation. We therefore hypothesized that tyrosine
      phosphorylation was required for Stat3 interaction with PKCdelta and subsequent
      PKCdelta-dependent phosphorylation of Stat3 Ser727. We developed an efficient
      transfection protocol for human monocytes. Expression of Stat3 containing a
      mutation in Tyr705 inhibited the association of PKCdelta with Stat3 and blocked
      Stat3 Ser727 phosphorylation, whereas transfection with wild-type Stat3 did not.
      Furthermore, by transfecting monocytes with Stat3 containing mutations in Tyr705
      or Ser727 or with wild-type Stat3, we demonstrated that both Stat3 tyrosine and
      serine phosphorylations are required for optimal binding of Stat3 with DNA and
      maximal expression of 15-lipoxygenase, an important regulator of inflammation and
      apoptosis.

PMID- 16951339
TI  - Reduced susceptibility of recombinant polyclonal antibodies to inhibitory anti
      variable domain antibody responses.
AB  - The immunogenicity of therapeutic Abs is a concern as anti-drug Abs may impact
      negatively on the pharmacodynamics and safety profile of Ab drugs. The factors
      governing induction of anti-drug Abs are not fully understood. In this study, we
      describe a model based on mouse-human chimeric Abs for the study of Ab
      immunogenicity in vivo. Six chimeric Abs containing human V regions and mouse C
      regions were generated from six human anti-Rhesus D Abs and the Ag-binding
      characteristics of the parental human Abs were retained. Analysis of the immune
      response toward the individual chimeric Abs revealed the induction of anti
      variable domain Abs including anti-idiotypic Abs against some of these, thereby
      demonstrating the applicability of the model for studying anti-drug Ab responses
      in vivo. Immunization of BALB/c, C57, and outbred NMRI mice with a polyclonal
      composition consisting of all six chimeric Abs demonstrated that the
      immunogenicity of the individual Abs was haplotype dependent. Chimeric Abs, which
      were nonimmunogenic when administered individually, did not become immunogenic as
      part of the polyclonal composition, implying the absence of epitope spreading. Ex
      vivo Ab-binding studies established a clear correlation between the level of
      immunogenicity of the Abs comprised in the composition and the impact on the
      pharmacology of the Abs. These analyses demonstrate that under these conditions
      this polyclonal Ab composition was generally less susceptible to blocking Abs
      than the respective mAbs.

PMID- 16951340
TI  - Evidence that marginal zone B cells possess an enhanced secretory apparatus and
      exhibit superior secretory activity.
AB  - Marginal zone B (MZB) cells are the first splenic B cells to initiate Ab
      secretion against polysaccharide-encapsulated Ags in vivo. This swift MZB cell
      response can be reproduced in vitro as LPS treatment induces Ab secretion in as
      little as 12 h. Conversely, in vitro LPS treatment of splenic follicular B (FOB)
      cells results in Ab secretion after 2-3 days. The basis for these distinct
      response kinetics is not understood. We performed ex vivo analysis of resting and
      LPS-stimulated murine MZB and FOB cells and found that MZB cells express higher
      levels of the LPS TLR complex RP105/MD-1 and respond to much lower concentrations
      of LPS than do FOB cells. Furthermore, increasing doses of LPS do not accelerate
      the kinetics by which FOB cells transition into Ab secretion. Ultrastructural
      analysis of resting cells demonstrated that rough endoplasmic reticulum is more
      abundant in MZB cells than in FOB cells. Additionally, RT-PCR and immunoblot
      analyses revealed that numerous endoplasmic reticulum resident chaperones and
      folding enzymes are expressed at greater levels in resting MZB cells than in
      resting FOB cells. Although both LPS-stimulated MZB and FOB cells increase
      expression of these factors, MZB cells exhibit a more rapid increase that
      correlates with accelerated kinetics of Ab secretion and higher per cell output
      of secreted IgM. These data indicate that MZB cells are equipped for exquisite
      sensitivity to bacterial components like LPS and poised for rapid, robust Ab
      production, making MZB cells ideally suited as frontline defenders in humoral
      immunity.

PMID- 16951341
TI  - Receptor activator of NF-kappa B ligand and osteoprotegerin regulate
      proinflammatory cytokine production in mice.
AB  - Receptor activator of NF-kappaB ligand (RANKL) is a membrane-bound or soluble
      cytokine essential for osteoclast differentiation, whereas the decoy receptor
      osteoprotegerin (OPG) masks RANKL activity. In mouse serum, both soluble RANKL
      and OPG are detectable. We observed that mice injected with LPS showed
      significantly down-regulated serum RANKL levels, whereas serum OPG levels were up
      regulated. However, the roles of RANKL and OPG in innate immunity remain obscure.
      We found that RANKL pretreatment suppressed production of proinflammatory
      cytokines in macrophages in response to stimulation by bacteria and their
      components. Furthermore, such RANKL-induced tolerance in macrophages was
      inhibited by GM-CSF treatment, which blocks RANKL signaling. RANKL-induced
      tolerance occurred in the absence of c-Fos, which is essential for osteoclast
      differentiation. In mice lacking OPG, LPS-induced production of proinflammatory
      cytokines was reduced, whereas in mice lacking RANKL, it was increased, and
      lethality following LPS injection was also elevated, suggesting that constitutive
      activities of RANKL suppress cytokine responsiveness to LPS in vivo. Strikingly,
      prior administration of RANKL protected mice from LPS-induced death. These data
      reveal prophylactic potential of RANKL in acute inflammatory diseases.

PMID- 16951342
TI  - Immature dendritic cells suppress collagen-induced arthritis by in vivo expansion
      of CD49b+ regulatory T cells.
AB  - Dendritic cells (DCs) are specialized APCs with an important role in the
      initiation and regulation of immune responses. Immature DCs (iDCs) reportedly
      mediate tolerance in the absence of maturation/inflammatory stimuli, presumably
      by the induction of regulatory T cells. In this study, we show for the first time
      that repetitive iDC injections trigger the expansion of a novel regulatory
      population with high immunomodulatory properties, able to protect mice from
      collagen-induced arthritis. These regulatory T cells are characterized by the
      expression of the CD49b molecule and correspond to a CD4+ alpha
      galactosylceramide/CD1d-nonrestricted T cell population producing IL-10. Adoptive
      transfer of < 10(5) TCRbeta+ CD49b+ cells isolated from the liver of iDCs
      vaccinated mice, conferred a complete protection against arthritis. This
      protection was associated with an attenuation of the B and T cell response
      associated with a local secretion of IL-10. Thus, together these data demonstrate
      that iDCs can expand and activate a novel regulatory population of CD49b+ T
      cells, with high immunosuppressive potential able to mediate protection against a
      systemic autoimmune disease.

PMID- 16951343
TI  - Transgenic expression of the viral FLIP MC159 causes lpr/gld-like
      lymphoproliferation and autoimmunity.
AB  - Death receptor-induced programmed cell death (PCD) is crucial for the maintenance
      of immune homeostasis. However, interference of downstream death receptor
      signaling by genetic ablation or transgenic (Tg) expression of different
      apoptosis inhibitors often impairs lymphocyte activation. The viral FLICE
      (caspase-8)-like inhibitor proteins (v-FLIPs) are potent inhibitors of death
      receptor-induced apoptosis and programmed necrosis. We generated Tg mice
      expressing the v-FLIP MC159 from Molluscum contagiosum virus under the control of
      the H2Kb class I MHC promoter to examine the role of death receptor-induced PCD
      in the control of immune functions and homeostasis. We found that expression of
      MC159 led to lymphoproliferation and autoimmunity as exemplified by T and B
      lymphocyte expansion, accumulation of TCRalphabeta+ CD3+ B220+ CD4- CD8-
      lymphocytes in secondary lymphoid organs, elevated serum Ig levels, and increased
      anti-dsDNA Ab titers. These phenotypes were caused by defective death receptor
      induced apoptosis, but not by defective passive cell death in the absence of
      mitogenic stimulation. Lymphocyte activation was normal, as demonstrated by
      normal thymidine incorporation and CSFE dilution of T cells stimulated with anti
      CD3 and anti-CD28 Abs. In addition, effector CD8+ T cell responses to acute and
      memory lymphocytic choriomeningitis virus infections were unaffected in the Tg
      mice. These phenotypes are reminiscent of the lpr and gld mice, and show that the
      v-FLIP MC159 is a bona fide PCD inhibitor that does not interfere with other
      essential lymphocyte functions. Thus, the MC159-Tg mice provide a model to study
      the effects of PCD in immune responses without hampering other important
      lymphocyte functions.

PMID- 16951344
TI  - Impaired memory CD8 T cell development in the absence of methyl-CpG-binding
      domain protein 2.
AB  - Intracellular differentiation events that determine which cells develop into
      memory CD8 T cells are currently incompletely understood. Methyl-CpG-binding
      domain protein 2 (MBD2) is a transcriptional repressor that binds to methylated
      DNA and mediates the biological consequences of epigenetic gene methylation. The
      role of MBD2 during the differentiation of naive CD8 T cells into effector and
      memory cells was determined following acute infection of MBD2-deficient mice with
      lymphocytic choriomeningitis virus. Despite rapid viral clearance and an
      efficient primary effector CD8 T cell response, reduced numbers of Ag-specific
      memory CD8 T cells were observed. Importantly, the appearance of precursor memory
      cells (IL-7Ralphahigh) was delayed. The remaining MBD2(-/-) memory cells were not
      fully protective during rechallenge, and memory cell characteristics were altered
      with regard to surface markers (IL-7Ralpha, KLRG-1, CD27, and others) and
      cytokine production. The defect was CD8 T cell intrinsic, because memory cell
      development was also delayed when MBD2(-/-) CD8 T cells were adoptively
      transferred into SCID mice. These data demonstrate that MBD2 is a previously
      unrecognized intracellular factor required for the efficient generation of
      protective memory CD8 T cells.

PMID- 16951345
TI  - The cathepsin B inhibitor, z-FA-FMK, inhibits human T cell proliferation in vitro
      and modulates host response to pneumococcal infection in vivo.
AB  - The cathepsin B inhibitor, benzyloxycarbonyl-phenyl-alanyl-fluoromethylketone (z
      FA-FMK) at nontoxic doses was found to be immunosuppressive and repressed human T
      cell proliferation induced by mitogens and IL-2 in vitro. We showed that z-FA-FMK
      suppresses the secretion of IL-2 and IFN-gamma as well as the expression of IL-2R
      alpha-chain (CD25) in activated T cells, whereas the expression of the early
      activated T cell marker, CD69, was unaffected. Furthermore, z-FA-FMK blocks NF
      kappaB activation, inhibits T cell blast formation, and prevents cells from
      entering and leaving the cell cycle. z-FA-FMK inhibits the processing of caspase
      8 and caspase-3 to their respective subunits in resting T cells stimulated
      through the Ag receptor, but has no effect on the activation of these caspases
      during Fas-induced apoptosis in proliferating T cells. When administered in vivo,
      z-FA-FMK significantly increased pneumococcal growth in both lungs and blood,
      compared with controls, in a mouse model of intranasal pneumococcal infection.
      Because host response to bronchopneumonia in mice is T cell dependent, our
      collective results demonstrated that z-FA-FMK is immunosuppressive in vitro and
      in vivo.

PMID- 16951347
TI  - IgG Fc receptor III homologues in nonhuman primate species: genetic
      characterization and ligand interactions.
AB  - Ig Fc receptors bind to immune complexes through interactions with the Fc regions
      of specific Ab subclasses to initiate or inhibit the defense mechanisms of the
      leukocytes on which they are expressed. The mechanism of action of IgG-based
      therapeutic molecules, which are routinely evaluated in nonhuman primate models,
      involves binding to the low-affinity FcRIII (CD16). The premise that IgG/CD16
      interactions in nonhuman primates mimic those present in humans has not been
      evaluated. Therefore, we have identified and characterized CD16 and associated
      TCR zeta-chain homologues in rhesus macaques, cynomolgus macaques, baboons, and
      sooty mangabeys. Similar to humans, CD16 expression was detected on a lymphocyte
      subpopulation, on monocytes, and on neutrophils of sooty mangabeys. However, CD16
      was detected only on a lymphocyte subpopulation and on monocytes in macaques and
      baboons. A nonhuman primate rCD16 generated in HeLa cells interacted with human
      IgG1 and IgG2. By contrast, human CD16 binds to IgG1 and IgG3. As shown for
      humans, the mAb 3G8 was able to block IgG binding to nonhuman primate CD16 and
      inhibition of nonhuman primate CD16 N-glycosylation enhanced IgG binding.
      Clearly, differences in interaction with IgG subclasses and in cell-type
      expression should be considered when using these models for in vivo evaluation of
      therapeutic Abs.

PMID- 16951346
TI  - Constitutive expression of murine decay-accelerating factor 1 is controlled by
      the transcription factor Sp1.
AB  - The complement regulatory protein decay-accelerating factor (DAF or CD55)
      protects host tissue from complement-mediated injury by inhibiting the classical
      and alternative complement pathways. Besides its role in complement regulation,
      DAF has also been shown to be a key player in T cell immunity. Modulation of DAF
      expression could therefore represent a critical regulatory mechanism in both
      innate and adaptive immune responses. To identify and characterize key
      transcriptional regulatory elements controlling mouse Daf1 expression, a 2.5-kb
      fragment corresponding to the 5' flanking region of the mouse Daf1 gene was
      cloned. Sequence analysis showed that the mouse Daf1 promoter lacks conventional
      TATA and CCAAT boxes and displays a high guanine and cytosine content. RACE was
      used to identify one major and two minor transcription start sites 47, 20, and 17
      bp upstream of the translational codon. Positive and negative regulatory regions
      were identified by transiently transfecting sequential 5'deletion constructs of
      the 5'flanking region into NIH/3T3, M12.4, and RAW264.7 cells. Mutational
      analyses of the promoter region combined with Sp1-specific ELISA showed that the
      transcription factor Sp1 is required for basal transcription and LPS-induced
      expression of the Daf1 gene. These findings provide new information on the
      regulation of the mouse Daf1 promoter and will facilitate further studies on the
      expression of Daf1 during immune responses.

PMID- 16951348
TI  - A model for TCR gene segment use.
AB  - The TCR alpha-chain is assembled by somatic recombination of variable (V) and
      joining (J) gene segments at the CD4+ CD8+ stage of development. In this study,
      we present the first analytical model for deletional rearrangement and show that
      it is consistent with almost all available data on Valpha Jalpha use in mice and
      humans. A key feature of the model is that both "local" and "express service"
      models of rearrangement can be obtained by varying a single parameter that
      describes the number of gene segments accessible at a time. We find that the
      window is much larger for Valpha segments than Jalpha segments, which reconciles
      seemingly conflicting data for the former. Implications for the properties of the
      repertoire as a whole and experiments that seek to probe them are discussed.
      Special considerations for allelic inclusion are treated in the Appendices.

PMID- 16951349
TI  - Epigenetic regulation during B cell differentiation controls CIITA promoter
      accessibility.
AB  - B cell to plasma cell maturation is marked by the loss of MHC class II
      expression. This loss is due to the silencing of the MHC class II transcriptional
      coactivator CIITA. In this study, experiments to identify the molecular mechanism
      responsible for CIITA silencing were conducted. CIITA is expressed from four
      promoters in humans, of which promoter III (pIII) controls the majority of B cell
      mediated expression. Chromatin immunoprecipitation assays were used to establish
      the histone code for pIII and determine the differences between B cells and
      plasma cells. Specific histone modifications associated with accessible promoters
      and transcriptionally active genes were observed at pIII in B cells but not in
      plasma cells. A reciprocal exchange of histone H3 lysine 9 acetylation to
      methylation was also observed between B cells and plasma cells. The lack of
      histone acetylation correlated with an absence of transcription factor binding to
      pIII, particularly that of Sp1, PU.1, CREB, and E47. Intriguingly, changes in
      chromatin architecture of the 13-kb region encompassing all CIITA promoters
      showed a remarkable deficit in histone H3 and H4 acetylation in plasma cells,
      suggesting that the mechanism of silencing is global. When primary B cells were
      differentiated ex vivo, most of the histone marks associated with pIII activation
      and expression were lost within 24 h. The results demonstrate that CIITA
      silencing occurs by controlling chromatin accessibility through a multistep
      mechanism that includes the loss of histone acetylation and transcription factor
      binding, and the acquisition of repressive histone methylation marks.

PMID- 16951350
TI  - Recombinant HLA-DP2 binds beryllium and tolerizes beryllium-specific pathogenic
      CD4+ T cells.
AB  - Chronic beryllium disease is a lung disorder caused by beryllium exposure in the
      workplace and is characterized by granulomatous inflammation and the accumulation
      of beryllium-specific, HLA-DP2-restricted CD4+ T lymphocytes in the lung that
      proliferate and secrete Th1-type cytokines. To characterize the interaction among
      HLA-DP2, beryllium, and CD4+ T cells, we constructed rHLA-DP2 and rHLA-DP4
      molecules consisting of the alpha-1 and beta-1 domains of the HLA-DP molecules
      genetically linked into single polypeptide chains. Peptide binding to rHLA-DP2
      and rHLA-DP4 was consistent with previously published peptide-binding motifs for
      these MHC class II molecules, with peptide binding dominated by aromatic residues
      in the P1 pocket. 9Be nuclear magnetic resonance spectroscopy showed that
      beryllium binds to the HLA-DP2-derived molecule, with no binding to the HLA-DP4
      molecule that differs from DP2 by four amino acid residues. Using beryllium
      specific CD4+ T cell lines derived from the lungs of chronic beryllium disease
      patients, beryllium presentation to those cells was independent of Ag processing
      because fixed APCs were capable of presenting BeSO4 and inducing T cell
      proliferation. Exposure of beryllium-specific CD4+ T cells to BeSO4 -pulsed,
      plate-bound rHLA-DP2 molecules induced IFN-gamma secretion. In addition,
      pretreatment of beryllium-specific CD4+ T cells with BeSO4-pulsed, plate-bound
      HLA-DP2 blocked proliferation and IL-2 secretion upon re-exposure to beryllium
      presented by APCs. Thus, the rHLA-DP2 molecules described herein provide a
      template for engineering variants that retain the ability to tolerize pathogenic
      CD4+ T cells, but do so in the absence of the beryllium Ag.

PMID- 16951351
TI  - Crystallographic structure of a rheumatoid arthritis MHC susceptibility allele,
      HLA-DR1 (DRB1*0101), complexed with the immunodominant determinant of human type
      II collagen.
AB  - The expression of HLA-DR1 (DRB1*0101) is associated with an enhanced risk for
      developing rheumatoid arthritis (RA). To study its function, we have solved the
      three-dimensional structure of HLA-DR1 complexed with a candidate RA autoantigen,
      the human type II collagen peptide CII (259-273). Based on these structural data,
      the CII peptide is anchored by Phe263 at the P1 position and Glu266 at P4.
      Surprisingly, the Lys at the P2 position appears to play a dual role by
      participating in peptide binding via interactions with DRB1-His81 and Asn82, and
      TCR interaction, based on functional assays. The CII peptide is also anchored by
      the P4 Glu266 residue through an ionic interaction with DRB1-Arg71 and Glu28.
      Participation of DRB1-Arg71 is significant because it is part of the shared
      epitope expressed by DR alleles associated with RA susceptibility. Potential
      anchor residues at P6 and P9 of the CII peptide are both Gly, and the lack of
      side chains at these positions appears to result in both a narrower binding
      groove with the peptide protruding out of the groove at this end of the DR1
      molecule. From the TCR perspective, the P2-Lys264, P5-Arg267, and P8-Lys270
      residues are all oriented away from the binding groove and collectively represent
      a positive charged interface for CII-specific TCR binding. Comparison of the DR1
      CII structure to a DR1-hemagglutinin peptide structure revealed that the binding
      of these two peptides generates significantly different interfaces for the
      interaction with their respective Ag-specific TCRs.

PMID- 16951352
TI  - Strong TCR conservation and altered T cell cross-reactivity characterize a B*57
      restricted immune response in HIV-1 infection.
AB  - HLA-B*57 is associated with slower disease progression to AIDS, and CD8+ T cell
      responses to B*57-restricted epitopes are thought to contribute to this
      protective effect. In this study, we evaluate the B*57-restricted p24 KAFSPEVIPMF
      (KF11) immune response which is immunodominant during chronic infection.
      Previously, we observed that the KF11 clade variants KGFNPEVIPMF [A2G,S4N] and
      KAFNPEIIMPF [S4N,V7I], sharing a position 4 mutation, are differentially
      recognized by KF11-specific T cells. By combining structural and cellular
      studies, we now demonstrate that the KF11 and [A2G,S4N] epitopes induce distinct
      functional responses in [A2G,S4N] and KF11-specific T cells, respectively,
      despite minimal structural differences between the individual B*57-peptide
      complexes. Recently, we also elucidated the highly distinct structure of KF11 in
      complex with B*5703, and have now characterized the CD8+ T cell repertoire
      recognizing this epitope. We now report striking features of TCR conservation
      both in terms of TCR Valpha and Vbeta chain usage, and throughout the
      hypervariable region. Collectively, our findings highlight unusual features of
      the B*5701/B*5703-KF11-specific immune responses which could influence disease
      progression and that might be important to consider when designing future vaccine
      regimens.

PMID- 16951353
TI  - Fluorescence-activated cell sorting and cloning of bona fide CD8+ CTL with
      reversible MHC-peptide and antibody Fab' conjugates.
AB  - The isolation of subsets of Ag-specific T cells for in vitro and in vivo studies
      by FACS is compromised by the fact that the soluble MHC-peptide complexes and Abs
      used for staining, especially when combined, induce unwanted T cell activation
      and eventually apoptosis. This is especially a problem for CD8+ CTL, which are
      susceptible to activation-dependent cell death. In this study, we show that
      reversible MHC-peptide complexes (tetramers) can be prepared by conjugating MHC
      peptide monomers with desthiobiotin (DTB; also called dethiobiotin) and
      multimerization by reaction with fluorescent streptavidin. While in the cold
      these reagents are stable and allow good staining, they rapidly dissociate in
      monomers at elevated temperatures, especially in the presence of free biotin.
      FACS cloning of Melan-A (MART-1)-specific CTL from a melanoma-infiltrated lymph
      node with reversible HLA-A2 Melan-A26-35 multimers yielded over two times more
      clones than when using the conventional biotin-containing multimers. CTL clones
      obtained by means of reversible multimers killed Melan-A-positive tumor cells
      more efficiently as compared with clones obtained with the stable multimers.
      Among the CTL obtained with the reversible multimers, but much less among those
      obtained with the stable multimers, a high proportion of clones exhibited high
      functional and physical avidity and died upon incubation with soluble MHC-peptide
      complexes. Finally, we show that Fab' of an anti-CD8 Ab can be converted in
      reversible DTB streptavidin conjugates the same way. These DTB reagents
      efficiently and reversibly stained murine and human CTL without affecting their
      viability.

PMID- 16951354
TI  - Sites in the CH3 domain of human IgA1 that influence sensitivity to bacterial
      IgA1 proteases.
AB  - The influence of regions, other than the hinge, on the susceptibility of human
      IgA1 to cleavage by diverse bacterial IgA1 proteases, was examined using IgA1
      mutants bearing amino acid deletions, substitutions, and domain swaps. IgA1
      lacking the tailpiece retained its susceptibility to cleavage by all of the IgA1
      proteases. The domain swap molecule alpha1alpha2gamma3, in which the CH3 domain
      of IgA1 was exchanged for that of human IgG1, was resistant to cleavage with the
      type 1 and 2 serine IgA1 proteases of Neisseria meningitidis, Neisseria
      gonorrhoeae, and Haemophilus influenzae, but remained sensitive to cleavage with
      the metallo-IgA1 proteases of Streptococcus pneumoniae, Streptococcus oralis,
      Streptococcus sanguis, and Streptococcus mitis. Substitution of the IgA1 Calpha3
      domain motif Pro440 -Phe443 into the corresponding position in the Cgamma3 domain
      of alpha1alpha2gamma3 resulted now in sensitivity to the type 2 IgA1 protease of
      N. meningitidis, indicating the possible requirement of these amino acids for
      sensitivity to this protease. For the H. influenzae type 2 protease, resistance
      of an IgA1 mutant in which the CH3 domain residues 399-409 were exchanged with
      those from IgG1, but sensitivity of mutant HuBovalpha3 in which the Calpha3
      domain of bovine IgA replaces that of human IgA1, suggests that CH3 domain
      residues Glu403, Gln406, and Thr409 influence sensitivity to this enzyme. Hence,
      unlike the situation with the metallo-IgA1 proteases of Streptococcus spp., the
      sensitivity of human IgA1 to cleavage with the serine IgA1 proteases of Neisseria
      and Haemophilus involves their binding to different sites specifically in the CH3
      domain.

PMID- 16951355
TI  - Structural basis of inducible costimulator ligand costimulatory function:
      determination of the cell surface oligomeric state and functional mapping of the
      receptor binding site of the protein.
AB  - Inducible costimulator (ICOS) ligand (ICOSL), a B7-related transmembrane
      glycoprotein with extracellular IgV and IgC domains, binds to ICOS on activated T
      cells and delivers a positive costimulatory signal for optimal T cell function.
      Toward determining the structural features of ICOSL crucial for its costimulatory
      function, the present study shows that ICOSL displays a marked oligomerization
      potential, resembling more like B7-1 than B7-2. Use of ICOSL constructs lacking
      either the IgC or IgV domain demonstrates that receptor binding is mediated
      solely by the IgV domain but requires the IgC domain for maintaining the
      structural integrity of the protein. To map further the receptor recognition
      surface on ICOSL, a homology-based protein structure model of the ICOS:ICOSL
      complex was constructed. Based on predictions from the model, a series of
      mutations were generated targeting the potential receptor binding surface on
      ICOSL, and the mutants were tested for their biological function in terms of ICOS
      binding and T cell costimulation ability. The results provide experimental
      validation of the model and show that the receptor binding site on ICOSL is
      constituted chiefly by aromatic/hydrophobic residues. Critical ICOSL residues
      essential for ICOS binding map to the GFCC'C'' beta-sheet face of the IgV domain
      and approximately overlap with the B7-1/B7-2 motif(s) that recognize CD28/CTLA-4.
      Altogether, similar structural features of ICOSL and B7 isoforms suggest a close
      evolutionary relationship between these costimulatory ligands, yet differences at
      the same time explain their unique specificity for the cognate binding partners,
      ICOS and CD28/CTLA-4, respectively.

PMID- 16951356
TI  - Mapping the binding site on CD8 beta for MHC class I reveals mutants with
      enhanced binding.
AB  - In an effective immune response, CD8+ T cell recognition of virally derived Ag,
      bound to MHC class I, results in killing of infected cells. The CD8alphabeta
      heterodimer acts as a coreceptor with the TCR, to enhance sensitivity of the T
      cells to peptide/MHC class I, and is two orders of magnitude more efficient as a
      coreceptor than the CD8alphaalpha. To understand the important interaction
      between CD8alphabeta and MHC class I, we created a panel of CD8beta mutants and
      identified mutations in the CDR1, CDR2, and CDR3 loops that decreased binding to
      MHC class I tetramers as well as mutations that enhanced binding. We tested the
      coreceptor function of a subset of reducing and enhancing mutants using a T cell
      hybridoma and found similar reducing and enhancing effects. CD8beta-enhancing
      mutants could be useful for immunotherapy by transduction into T cells to enhance
      T cell responses against weak Ags such as those expressed by tumors. We also
      addressed the question of the orientation of CD8alphabeta with MHC class I using
      CD8alpha mutants expressed as a heterodimer with wild-type CD8alpha or CD8beta.
      The partial rescuing of binding with wild-type CD8beta compared with wild-type
      CD8alpha is consistent with models in which either the topology of CD8alphaalpha
      and CD8alphabeta binding to MHC class I is different or CD8alphabeta is capable
      of binding in both the T cell membrane proximal and distal positions.

PMID- 16951357
TI  - Evolution of the CD4 family: teleost fish possess two divergent forms of CD4 in
      addition to lymphocyte activation gene-3.
AB  - The T cell coreceptor CD4 is a transmembrane glycoprotein belonging to the Ig
      superfamily and is essential for cell-mediated immunity. Two different genes were
      identified in rainbow trout that resemble mammalian CD4. One (trout CD4) encodes
      four extracellular Ig domains reminiscent of mammalian CD4, whereas the other
      (CD4REL) codes for two Ig domains. Structural motifs within the amino acid
      sequences suggest that the two Ig domains of CD4REL duplicated to generate the
      four-domain molecule of CD4 and the related gene, lymphocyte activation gene-3.
      Here we present evidence that both of these molecules in trout are homologous to
      mammalian CD4 and that teleosts encode an additional CD4 family member,
      lymphocyte activation gene-3, which is a marker for activated T cells. The
      syntenic relationships of similar genes in other teleost and non-fish genomes
      provide evidence for the likely evolution of CD4-related molecules in
      vertebrates, with CD4REL likely representing the primordial form in fish.
      Expression of both CD4 genes is highest in the thymus and spleen, and mRNA
      expression of these genes is limited to surface IgM- lymphocytes. consistent with
      a role for T cell functionality. Finally, the intracellular regions of both CD4
      and CD4REL possess the canonical CXC motif involved in the interaction of CD4
      with p56LCK, implying that similar mechanisms for CD4+ T cell activation are
      present in all vertebrates. Our results therefore raise new questions about T
      cell development and functionality in lower vertebrates that cannot be answered
      by current mammalian models and, thus, is of fundamental importance for
      understanding the evolution of cell-mediated immunity in gnathosomes.

PMID- 16951358
TI  - Backcross and partial advanced intercross analysis of nonobese diabetic gene
      mediated effects on collagen-induced arthritis reveals an interactive effect by
      two major loci.
AB  - Genetic segregation analysis between NOD and C57BL strains have been used to
      identify loci associated with autoimmune disease. Only two loci (Cia2 and Cia9)
      had earlier been found to control development of arthritis, whereas none of the
      previously identified diabetes loci was of significance for arthritis. We have
      now made a high-powered analysis of a backcross of NOD genes on to the B10.Q
      strain for association with collagen-induced arthritis. We could confirm
      relevance of both Cia2 and Cia9 as well as the interaction between them, but we
      did not identify any other significant arthritis loci. Immune cellular subtyping
      revealed that Cia2 was also associated with the number of blood macrophages.
      Congenic strains of the Cia2 and Cia9 loci on the B10.Q background were made and
      used to establish a partial advanced intercross (PAI). Testing the PAI mice for
      development of collagen-induced arthritis confirmed the loci and the interactions
      and also indicated that at least two genes contribute to the Cia9 locus.
      Furthermore, it clearly showed that Cia2 is dominant protective but that the
      protection is not complete. Because these results may indicate that the Cia2
      effect on arthritis is not only due to the deficiency of the complement C5, we
      analyzed complement functions in the Cia2 congenics as well as the PAI mice.
      These data show that not only arthritis but also C5-dependent complement activity
      is dominantly suppressed, confirming that C5 is one of the major genes explaining
      the Cia2 effect.

PMID- 16951359
TI  - Human cytomegalovirus alters localization of MHC class II and dendrite morphology
      in mature Langerhans cells.
AB  - Hemopoietic stem cell-derived mature Langerhans-type dendritic cells (LC) are
      susceptible to productive infection by human CMV (HCMV). To investigate the
      impact of infection on this cell type, we examined HLA-DR biosynthesis and
      trafficking in mature LC cultures exposed to HCMV. We found decreased surface HLA
      DR levels in viral Ag-positive as well as in Ag-negative mature LC. Inhibition of
      HLA-DR was independent of expression of unique short US2-US11 region gene
      products by HCMV. Indeed, exposure to UV-inactivated virus, but not to
      conditioned medium from infected cells, was sufficient to reduce HLA-DR on mature
      LC, implicating particle binding/penetration in this effect. Reduced surface
      levels reflected an altered distribution of HLA-DR because total cellular HLA-DR
      was not diminished. Accumulation of HLA-DR was not explained by altered cathepsin
      S activity. Mature, peptide-loaded HLA-DR molecules were retained within cells,
      as assessed by the proportion of SDS-stable HLA-DR dimers. A block in egress was
      implicated, as endocytosis of surface HLA-DR was not increased.
      Immunofluorescence microscopy corroborated the intracellular retention of HLA-DR
      and revealed markedly fewer HLA-DR-positive dendritic projections in infected
      mature LC. Unexpectedly, light microscopic analyses showed a dramatic loss of the
      dendrites themselves and immunofluorescence revealed that cytoskeletal elements
      crucial for the formation and maintenance of dendrites are disrupted in viral Ag
      positive cells. Consistent with these dendrite effects, HCMV-infected mature LC
      exhibit markedly reduced chemotaxis in response to lymphoid chemokines. Thus,
      HCMV impedes MHC class II molecule trafficking, dendritic projections, and
      migration of mature LC. These changes likely contribute to the reduced activation
      of CD4+ T cells by HCMV-infected mature LC.

PMID- 16951360
TI  - TNF is important for pathogen control and limits brain damage in murine cerebral
      listeriosis.
AB  - Cerebral listeriosis is a life-threatening disease. However, little is known
      about the bacterial virulence factors responsible for the severe course of
      disease and the factors of the immune system contributing to the control of
      Listeria monocytogenes (LM) or even to the damage of the brain. To analyze the
      importance of the actA gene of LM, which mediates cell-to-cell spread of
      intracellular LM, the function of TNF in murine cerebral listeriosis was studied.
      C57BL/6 mice survived an intracerebral (i.c.) infection with actA-deficient LM,
      but succumbed to infection with wild-type (WT) LM. Upon infection with actA
      deficient LM, macrophages and microglial cells rapidly, and later LM-specific CD4
      and CD8 T cells, produced TNF. In contrast to WT mice, TNF-deficient animals
      succumbed to the infection within 4 days due to failure of control of LM.
      Histology identified a more severe meningoencephalitis, brain edema, and neuronal
      damage, but a reduced inducible NO synthase expression in TNF-deficient mice.
      Reciprocal bone marrow chimeras between WT and TNF-deficient mice revealed that
      hematogenously derived TNF was essential for survival, whereas TNF produced by
      brain-resident cells was less important. Death of TNF-deficient mice could be
      prevented by LM-specific T cells induced by an active immunization before i.c.
      infection. However, brain pathology and inflammation of immunized TNF-deficient
      mice were still more severe. In conclusion, these findings identify a crucial
      role of TNF for the i.c. control of LM and survival of cerebral listeriosis,
      whereas TNF was not responsible for the destruction of brain tissue.

PMID- 16951361
TI  - Salmonella typhimurium coordinately regulates FliC location and reduces dendritic
      cell activation and antigen presentation to CD4+ T cells.
AB  - During infection, Salmonella transitions from an extracellular-phase (STEX,
      growth outside host cells) to an intracellular-phase (STIN, growth inside host
      cells): changes in gene expression mediate survival in the phagosome and modifies
      LPS and outer membrane protein expression, including altered production of FliC,
      an Ag recognized by immune CD4+ T cells. Previously, we demonstrated that
      systemic STIN bacteria repress FliC below the activation threshold of FliC
      specific T cells. In this study, we tested the hypothesis that changes in FliC
      compartmentalization and bacterial responses triggered during the transition from
      STEX to STIN combine to reduce the ability of APCs to present FliC to CD4+ T
      cells. Approximately 50% of the Salmonella-specific CD4+ T cells from Salmonella
      immune mice were FliC specific and produced IFN-gamma, demonstrating the potent
      immunogenicity of FliC. FliC expressed by STEX bacteria was efficiently presented
      by splenic APCs to FliC-specific CD4+ T cells in vitro. However, STIN bacteria,
      except when lysed, expressed FliC within a protected intracellular compartment
      and evaded stimulation of FliC-specific T cells. The combination of STIN-mediated
      responses that reduced FliC bioavailability were overcome by dendritic cells
      (DCs), which presented intracellular FliC within heat-killed bacteria; however,
      this ability was abrogated by live bacterial infection. Furthermore, STIN
      bacteria, unlike STEX, limited DC activation as measured by increased MHC class
      II, CD86, TNF-alpha, and IL-12 expression. These data indicate that STIN bacteria
      restrict FliC bioavailability by Ag compartmentalization, and together with STIN
      bacterial responses, limit DC maturation and cytokine production. Together, these
      mechanisms may restrain DC-mediated activation of FliC-specific CD4+ T cells.

PMID- 16951362
TI  - Aspergillus fumigatus induces innate immune responses in alveolar macrophages
      through the MAPK pathway independently of TLR2 and TLR4.
AB  - Aspergillus fumigatus causes invasive aspergillosis in immunosuppressed patients.
      In the immunocompetent host, inhaled conidia are cleared by alveolar macrophages.
      The signaling pathways of the alveolar macrophage involved in the clearance of A.
      fumigatus are poorly understood. Therefore, we investigated the role of TLRs in
      the immune response against A. fumigatus and their contribution to the signaling
      events triggered in murine alveolar macrophages upon infection with A. fumigatus
      conidia. Specifically, we examined the MAPKs and NF-kappaB activation and
      cytokine signaling. Our investigations revealed that immunocompetent TLR2, TLR4,
      and MyD88 knockout mice were not more susceptible to invasive aspergillosis as
      compared with wild-type mice and that the in vitro phosphorylation of the MAPKs
      ERK and p38 was not affected in TLR2, TLR4, or MyD88 knockout mice following
      stimulation with conidia. In vivo experiments suggest that ERK was an essential
      MAPK in the defense against A. fumigatus, whereas the activation of NF-kappaB
      appeared to play only a secondary role. In conclusion, our findings demonstrate
      that TLR2/4 recognition and MyD88 signaling are dispensable for the clearance of
      A. fumigatus under immunocompetent situations. Furthermore, our data stress the
      important role of ERK activation in innate immunity to A. fumigatus.

PMID- 16951363
TI  - Role of N-acetylglucosamine within core lipopolysaccharide of several species of
      gram-negative bacteria in targeting the DC-SIGN (CD209).
AB  - Our recent studies have shown that the dendritic cell-specific ICAM nonintegrin
      CD209 (DC-SIGN) specifically binds to the core LPS of Escherichia coli K12 (E.
      coli), promoting bacterial adherence and phagocytosis. In this current study, we
      attempted to map the sites within the core LPS that are directly involved in LPS
      DC-SIGN interaction. We took advantage of four sets of well-defined core LPS
      mutants, which are derived from E. coli, Salmonella enterica serovar Typhimurium,
      Neisseria gonorrhoeae, and Haemophilus ducreyi and determined interaction of each
      of these four sets with DC-SIGN. Our results demonstrated that N
      acetylglucosamine (GlcNAc) sugar residues within the core LPS in these bacteria
      play an essential role in targeting the DC-SIGN receptor. Our results also imply
      that DC-SIGN is an innate immune receptor and the interaction of bacterial core
      LPS and DC-SIGN may represent a primeval interaction between Gram-negative
      bacteria and host phagocytic cells.

PMID- 16951364
TI  - Listeriolysin O-deficient Listeria monocytogenes as a vaccine delivery vehicle:
      antigen-specific CD8 T cell priming and protective immunity.
AB  - Strains of Listeria monocytogenes (LM) that are deficient in the virulence factor
      listeriolysin O (LLO) are highly attenuated and are thought not to elicit
      protective immunity. This failure has been attributed to the inability of the
      bacterium to enter the host cell cytosol and access MHC class I Ag processing
      machinery. We reexamined this issue using recombinant strains of LM that are
      deficient in LLO but express an additional CD8 T cell epitope derived from
      lymphocytic choriomeningitis virus. After infection with LLO-deficient strains,
      we find sizable priming of epitope-specific CD8 T cells and the development of a
      functional memory cell population. Mice primed with the LLO-deficient LM strain
      are equally resistant against high-dose challenge with virulent LM as mice primed
      with wild-type virulent bacteria and also resist heterologous challenge with
      lymphocytic choriomeningitis virus. Interestingly, priming with a low dose of LLO
      deficient LM, which occurred in environment of reduced inflammation (IFN-gamma),
      allowed rapid amplification of Ag-specific CD8 T cells by booster immunization,
      despite an undetectable primary response. We conclude that the generation of
      protective immunity by LLO-deficient strains of LM does in fact occur and that
      this highly attenuated LM strain may be a useful platform for vaccine delivery.

PMID- 16951365
TI  - Chlamydia trachomatis infection alters the development of memory CD8+ T cells.
AB  - The obligate intracellular bacterium Chlamydia trachomatis is the most common
      cause of bacterial sexually transmitted disease in the United States and the
      leading cause of preventable blindness worldwide. Prior exposure to C.
      trachomatis has been shown to provide incomplete protection against subsequent
      infection. One possible explanation for the limited immunity afforded by prior C.
      trachomatis infection is poor activation of Chlamydia-specific memory CD8+ T
      cells. In this study, we examined the development of CD8+ memory T cell responses
      specific for the Chlamydia Ag CrpA. The percentage of CrpA63-71-specific T cells
      expressing an effector memory T cell phenotype (IL-7R+ CD62low) was dramatically
      diminished in mice immunized with C. trachomatis, compared with mice immunized
      with vaccinia virus expressing the CrpA protein. These alterations in memory T
      cell development were correlated with a significant reduction in the capacity of
      convalescent mice to mount an enhanced recall response to Chlamydia Ags, compared
      with the primary response. CrpA-specific memory T cells primed during VacCrpA
      infection also failed to respond to a challenge with Chlamydia. We therefore
      investigated whether C. trachomatis infection might have a global inhibitory
      effect on CD8+ T cell activation by coinfecting mice with C. trachomatis and
      Listeria monocytogenes and we found that the activation of Listeria-specific
      naive and memory CD8+ T cells was reduced in the presence of C. trachomatis.
      Together, these results suggest that Chlamydia is able to alter the development
      of CD8+ T cell responses during both primary and secondary infection, perhaps
      accounting for the incomplete protection provided by prior Chlamydia infection.

PMID- 16951366
TI  - Evaluation of passively transferred, nonneutralizing antibody-dependent cellular
      cytotoxicity-mediating IgG in protection of neonatal rhesus macaques against oral
      SIVmac251 challenge.
AB  - Previously, Ab-dependent cellular cytotoxicity (ADCC) was significantly
      correlated with reduced acute viremia upon intrarectal SIVmac251 challenge of
      immunized rhesus macaques. To directly assess ADCC protective efficacy, six
      neonatal macaques were infused s.c. with immune IgG (220 mg/kg) purified from the
      immunized animals and positive for ADCC and Ab-dependent cell-mediated viral
      inhibition (ADCVI) activities. Six neonates received control IgG. The neonates
      were challenged twice orally with 10(5) 50% inhibiting tissue culture-infective
      dose of SIVmac251 2 days post-IgG infusion. At challenge, plasma of neonates that
      received immune IgG did not neutralize SIVmac251 but had geometric mean ADCC
      titers of 48,130 and 232,850 against SIVmac251 -infected and gp120-coated
      targets, respectively. Peak ADCVI activity varied from 62 to 81%. ADCC activity
      declined with the 2-wk IgG half-life but was boosted at wk 4, together with de
      novo ADCC-mediating Abs in controls, by postchallenge viremia. ADCVI activity was
      similarly induced. No protection, assessed by viral burdens, CD4 counts, and time
      to euthanasia was observed. Possible factors contributing to the discrepancy
      between the previous correlation and lack of protection here include: the high
      oral challenge dose compared with the 400-fold lower intrarectal dose; the
      challenge route with regard to viral dissemination and distribution of infused
      IgG; insufficient NK effector activity and/or poor functionality in newborns;
      insufficient immune IgG; and the possibility that the previous correlation of
      ADCC with protection was augmented by cellular immune responses also present at
      challenge. Future studies should explore additional challenge routes in juvenile
      macaques using higher amounts of potent IgG preparations.

PMID- 16951367
TI  - Neutrophil signaling pathways activated by bacterial DNA stimulation.
AB  - We have previously shown that bacterial DNA activates human neutrophils in a CpG
      independent manner. In this study, we have characterized the signaling pathways
      involved in the activation mechanism. We found that p38 MAPK, ERK1/2, and JNK
      pathways, as well as the PI3K/Akt pathway, are activated by bacterial DNA. We
      also determined that bacterial DNA induces NF-kappaB and AP-1 activation. When
      analyzing the role of these pathways on neutrophil functions, we observed that up
      regulation of CD11b triggered by bacterial DNA was decreased by pharmacological
      inhibitors of the p38 MAPK, ERK1/2, and JNK, whereas stimulation of IL-8 release
      was dependent on p38, ERK1/2, and NF-kappaB. Moreover, we found that IL-8
      production was markedly enhanced by inhibition of JNK, suggesting that this
      pathway negatively modulates NF-kappaB-dependent transcription. We also observed
      that bacterial DNA stimulated IL-1R-associated kinase-1 kinase activity and its
      partial degradation. Finally, we determined that bacterial DNA stimulated CD11b
      up-regulation in TLR9(-/-) but not in MyD88(-/-) mouse neutrophils, supporting
      that bacterial DNA induces neutrophil activation through a TLR9-independent and
      MyD88-dependent pathway.

PMID- 16951368
TI  - Requirements for apoptotic cell contact in regulation of macrophage responses.
AB  - An important consequence of macrophage engulfment of apoptotic cells is
      suppression of inflammatory responses, which was first defined by assay of TNF
      alpha release stimulated by LPS. These effects are apparently mediated in part by
      paracrine effects of TGF-beta released by the subset of stimulated macrophages
      that ingest apoptotic cells, which suppresses neighboring cells. However, the
      apoptotic cell-derived signal that stimulates TGF-beta release, and the nature of
      any additional signals required for the anti-inflammatory response remain poorly
      defined. In this study, we investigate the requirements for apoptotic cell
      engagement of macrophage surface receptors in these responses. We show that the
      apoptotic cell receptors CD36 and alphavbeta3 contribute to apoptotic cell
      phagocytosis by mouse macrophages, but are not essential for anti-inflammatory
      responses, suggesting that the mechanisms of response and phagocytosis are
      separate. In further defining requirements for response, we confirm the
      importance of TGF-beta in suppression by apoptotic cells, and identify an
      additional level of control of these effects. We show that LPS-stimulated mouse
      macrophage TNF-alpha release is only suppressed if macrophages have first
      contacted apoptotic cells, and hence, bystander macrophages are refractory to TGF
      beta released by phagocytosing macrophages. We conclude that the profound
      suppression of LPS-driven TNF-alpha release by macrophage populations requires
      hitherto obscure contact-dependent licensing of macrophage responsiveness to TGF
      beta by apoptotic cells.

PMID- 16951369
TI  - Distinct in vivo roles of colony-stimulating factor-1 isoforms in renal
      inflammation.
AB  - CSF-1, the major regulator of macrophage (Mphi) development, has three
      biologically active isoforms: a membrane-spanning, cell surface glycoprotein, a
      secreted glycoprotein, and a secreted proteoglycan. We hypothesized that there
      are shared and unique roles of individual CSF-1 isoforms during renal
      inflammation. To test this, we evaluated transgenic mice only expressing the cell
      surface or precursors of the secreted CSF-1 isoforms for Mphi accumulation,
      activation, and Mphi-mediated tubular epithelial cell (TEC) apoptosis during
      unilateral ureteral obstruction. The only difference between secreted
      proteoglycan and secreted glycoprotein CSF-1 isoforms is the presence
      (proteoglycan) or absence (glycoprotein) of an 18-kDa chondroitin sulfate
      glycosaminoglycan. We report that 1) cell surface CSF-1 isoform is sufficient to
      restore Mphi accumulation, activation, and TEC apoptosis to wild-type levels and
      is substantially more effective than the secreted CSF-1 isoforms; 2) the
      chondroitin sulfate glycosaminoglycan facilitates Mphi accumulation, activation,
      and TEC apoptosis; 3) increasing the level of secreted proteoglycan CSF-1 in
      serum amplifies renal inflammation; and 4) cell-cell contact is required for Mphi
      to up-regulate CSF-1-dependent expression of IFN-gamma. Taken together, we have
      identified central roles for the cell surface CSF-1 and the chondroitin sulfate
      chain on secreted proteoglycan CSF-1 during renal inflammation.

PMID- 16951370
TI  - IL-17A induces eotaxin-1/CC chemokine ligand 11 expression in human airway smooth
      muscle cells: role of MAPK (Erk1/2, JNK, and p38) pathways.
AB  - Recently, IL-17A has been shown to be expressed in higher levels in respiratory
      secretions from asthmatics and correlated with airway hyperresponsiveness.
      Although these studies raise the possibility that IL-17A may influence allergic
      disease, the mechanisms remain unknown. In this study, we investigated the
      molecular mechanisms involved in IL-17A-mediated CC chemokine (eotaxin-1/CCL11)
      production from human airway smooth muscle (ASM) cells. We found that incubation
      of human ASM cells with rIL-17A resulted in a significant increase of eotaxin
      1/CCL11 release from ASM cells that was reduced by neutralizing anti-IL-17A mAb.
      Moreover, IL-17A significantly induced eotaxin-1/CCL11 release and mRNA
      expression, an effect that was abrogated with cycloheximide and actinomycin D
      treatment. Furthermore, transfection studies using a luciferase-driven reporter
      construct containing eotaxin-1/CCL11 proximal promoter showed that IL-17A induced
      eotaxin-1/CCL11 at the transcriptional level. IL-17A also enhanced significantly
      IL-1beta-mediated eotaxin-1/CCL11 mRNA, protein release, and promoter activity in
      ASM cells. Primary human ASM cells pretreated with inhibitors of MAPK p38,
      p42/p44 ERK, JNK, or JAK but not PI3K, showed a significant decrease in eotaxin
      1/CCL11 release upon IL-17A treatment. In addition, IL-17A mediated rapid
      phosphorylation of MAPK (p38, JNK, and p42/44 ERK) and STAT-3 but not STAT-6 or
      STAT-5 in ASM cells. Taken together, our data provide the first evidence of IL
      17A-induced eotaxin-1/CCL11 expression in ASM cells via MAPK (p38, p42/p44 ERK,
      JNK) signaling pathways. Our results raise the possibility that IL-17A may play a
      role in allergic asthma by inducing eotaxin-1/CCL11 production.

PMID- 16951371
TI  - Serum amyloid A is an endogenous ligand that differentially induces IL-12 and IL
      23.
AB  - The acute-phase proteins, C-reactive protein and serum amyloid A (SAA), are
      biomarkers of infection and inflammation. However, their precise role in immunity
      and inflammation remains undefined. We report in this study a novel property of
      SAA in the differential induction of Th1-type immunomodulatory cytokines IL-12
      and IL-23. In peripheral blood monocytes and the THP-1 monocytic cell line, SAA
      induces the expression of IL-12p40, a subunit shared by IL-12 and IL-23. SAA
      stimulated expression of IL-12p40 was rapid (< or = 4 h), sustainable (> or = 20
      h), potent (up to 3380 pg/ml/10(6) cells in 24 h), and insensitive to polymyxin B
      treatment. The SAA-stimulated IL-12p40 secretion required de novo protein
      synthesis and was accompanied by activation of the transcription factors NF
      kappaB and C/EBP. Expression of IL-12p40 required activation of the p38 MAPK and
      PI3K. Interestingly, the SAA-induced IL-12p40 production was accompanied by a
      sustained expression of IL-23p19, but not IL-12p35, resulting in preferential
      secretion of IL-23, but not IL-12. These results identify SAA as an endogenous
      ligand that potentially activates the IL-23/IL-17 pathway and present a novel
      mechanism for regulation of inflammation and immunity by an acute-phase protein.

PMID- 16951372
TI  - Induction of RelB participates in endotoxin tolerance.
AB  - Using a THP-1 human promonocyte model of endotoxin tolerance that simulates the
      sepsis leukocyte phenotype, we previously showed that tolerant cells remain
      responsive to LPS endotoxin with degradation of IkappaB in the cytosol and
      nuclear translocation and accumulation of p50 and p65 NF-kappaB transcription
      factors. Despite this, endotoxin-inducible NF-kappaB-dependent innate immunity
      genes, like IL-1beta, remained transcriptionally unresponsive in the tolerant
      phenotype, similar to the endotoxin tolerance observed in sepsis patients. In
      this study, we examined this paradox and found that RelB, another member of the
      NF-kappaB family, is induced during the establishment of tolerance. RelB
      expression correlated with IL-1beta repression, and sepsis patients showed
      increased RelB when compared with normal controls. Transient expression of RelB
      inhibited IL-1beta in endotoxin-responsive cells. In the inverse experiment,
      small inhibitory RNAs decreased RelB expression in tolerant cells and restored
      endotoxin induction of IL-1beta. When we examined tolerant cell extracts, we
      found transcriptionally inactive NF-kappaB p65/RelB heterodimers. Taken together,
      our findings demonstrate that RelB can repress proinflammatory gene expression,
      and suggest that RelB expression in sepsis patient blood leukocytes may play a
      role in the endotoxin-tolerant phenotype.

PMID- 16951373
TI  - MaxiK blockade selectively inhibits the lipopolysaccharide-induced I kappa B
      alpha /NF-kappa B signaling pathway in macrophages.
AB  - Macrophages have a pivotal function in innate immunity against bacterial
      infections. They are present in all body compartments and able to detect invading
      microorganisms with high sensitivity. LPS (endotoxin) of Gram-negative bacteria
      is among the most potent stimuli for macrophages and initiates a wide panel of
      cellular activation responses. The release of mediators such as TNF-alpha and ILs
      is essential for the initiation of a proinflammatory antibacterial response.
      Here, we show that blockade of the large-conductance Ca2+ -activated potassium
      channel MaxiK (BK) inhibited cytokine production from LPS-stimulated macrophages
      at the transcriptional level. This inhibitory effect of channel blockade was
      specific to stimulation with LPS and affected neither stimulation of macrophages
      with the cytokine TNF-alpha nor LPS-induced activation of cells that do not
      express MaxiK. Investigation of the upstream intracellular signaling pathways
      induced by LPS revealed that the blockade of MaxiK selectively inhibited
      signaling pathways leading to the activation of the transcription factor NF
      kappaB and the MAPK p38, whereas activation of ERK was unaffected. We present
      data supporting that proximal regulation of the inhibitory factor IkappaB-alpha
      is critically involved in the observed inhibition of NF-kappaB translocation.
      Using alveolar macrophages from rats, we could show that the necessity of MaxiK
      function in activation of NF-kappaB and subsequent cytokine production is not
      restricted to in vitro-generated monocyte-derived macrophages but also can be
      observed in primary cells. Thus, MaxiK appears to be a central molecule in the NF
      kappaB-dependent inflammatory response of macrophages to bacterial LPS.

PMID- 16951374
TI  - Complement activation contributes to both glomerular and tubulointerstitial
      damage in adriamycin nephropathy in mice.
AB  - Adriamycin nephropathy is a model of focal segmental glomerulosclerosis,
      characterized by proteinuria and progressive glomerulosclerosis and
      tubulointerstitial damage. In this study, we examined the role of complement in
      the etiology of adriamycin nephropathy in mice. We used mice deficient in C1q,
      factor D, C3, and CD59, and compared them with strain-matched controls. C3
      deposition occurred in the glomeruli of wild-type mice as early as 48 h following
      a single i.v. injection of adriamycin. C3-deficient mice developed significantly
      less proteinuria and less podocyte injury at day 3 postadriamycin than controls,
      suggesting that complement is important in mediating the early podocyte injury.
      At later time points, C3-deficient mice were protected from glomerulosclerosis,
      tubulointerstitial injury, and renal dysfunction. Factor D-deficient mice were
      also protected from renal disease, confirming the importance of alternative
      pathway activation in this model. In contrast, C1q-deficient mice developed
      similar disease to controls, indicating that the complement cascade was not
      activated via the classical pathway. CD59-deficient mice, which lack adequate
      control of C5b-9 formation, developed significantly worse histological and
      functional markers of renal disease than controls. Interestingly, although more
      C9 deposited in glomeruli of CD59-deficient mice than controls, in neither group
      was tubulointerstitial C9 staining apparent. We have demonstrated for the first
      time that alternative pathway activation of complement plays an important role in
      mediating the initial glomerular damage in this in vivo model of focal segmental
      glomerulosclerosis. Lack of CD59, which regulates the membrane attack complex,
      led to greater glomerular and tubulointerstitial injury.

PMID- 16951375
TI  - Selective ablation of matrix metalloproteinase-2 exacerbates experimental
      colitis: contrasting role of gelatinases in the pathogenesis of colitis.
AB  - The matrix metalloproteinases (MMPs), MMP-2 and MMP-9, share structural and
      substrate similarities and are up-regulated during human as well as animal models
      of inflammatory bowel disease. We recently demonstrated that epithelial-derived
      MMP-9 is an important mediator of inflammation and tissue damage in colitis. In
      this study, we examined the role of MMP-2 in acute colitis. Colitis was induced
      using two models, administration of dextran sodium sulfate (DSS) and Salmonella
      enterica subsp. serovar Typhimurium (S.T.). Bone marrow chimeras were performed
      using bone marrow cells from wild-type (WT) and MMP-2(-/-) mice. Colitis was
      evaluated by clinical symptoms, myeloperoxidase assay, and histology. MMP-2
      protein expression and activity were up-regulated in WT mice treated with DSS or
      S.T. MMP-2(-/-) mice were highly susceptible to the development of colitis
      induced by DSS (or S.T.) compared with WT. During inflammation, MMP-2 expression
      was increased in epithelial cells as well as in the infiltrating immune cells.
      Bone marrow chimera demonstrated that mucosa-derived MMP-2 was required for its
      protective effects toward colitis. Furthermore, we demonstrate that severe
      colitis in MMP-2(-/-) is not due to a compensatory increase in MMP-9. Finally, we
      show that MMP-2 regulates epithelial barrier function. In contrast to MMP-9,
      mucosa-derived MMP-2 may be a critical host factor that is involved in the
      prevention or cessation of the host response to luminal pathogens or toxins, an
      important aspect of healing and tissue resolution. Together, our data suggest
      that a critical balance between the two gelatinases determines the outcome of
      inflammatory response during acute colitis.

PMID- 16951376
TI  - Evidence of a functional role for interaction between ICAM-1 and nonmuscle alpha
      actinins in leukocyte diapedesis.
AB  - ICAM-1 is involved in both adhesion and extravasation of leukocytes to
      endothelium during inflammation. It has been shown that the ICAM-1 cytoplasmic
      domain is important for transendothelial migration of leukocytes but the precise
      molecular mechanisms involving the intracytoplasmic portion of ICAM-1 is not
      known. To characterize precisely the molecular scaffolding associated with ICAM
      1, we have used the yeast two-hybrid system, and we have identified six different
      proteins interacting with the ICAM-1 cytoplasmic domain. In this study, we report
      that the two forms of nonmuscle alpha-actinin (i.e., alpha-actinin 1 and alpha
      actinin 4) associate with ICAM-1, and that these interactions are essential for
      leukocyte extravasation. These interactions were further confirmed by
      coimmunoprecipitation and immunofluorescence in endothelial cells and in ICAM-1
      transfected Chinese hamster ovary cells. The function of these interactions was
      analyzed by point mutation of charged amino acids located on ICAM-1 cytoplasmic
      domain. We have identified three charged amino acids (arginine 480, lysine 481,
      and arginine 486) which are essential in the binding of alpha-actinins to the
      ICAM-1 cytoplasmic tail. Mutation of these amino acids completely inhibited ICAM
      1-mediated diapedesis. Experiments with siRNA inhibiting specifically alpha
      actinin 1 or alpha-actinin 4 on endothelial cells indicated that alpha-actinin 4
      had a major role in this phenomenon. Thus, our data demonstrate that ICAM-1
      directly interacts with cytoplasmic alpha-actinin 1 and 4 and that this
      interaction is required for leukocyte extravasation.

PMID- 16951377
TI  - Vascular endothelial growth factor receptor 2-based DNA immunization delays
      development of herpetic stromal keratitis by antiangiogenic effects.
AB  - Stromal keratitis (SK) is an immunoinflammatory eye lesion caused by HSV-1
      infection. One essential step in the pathogenesis is neovascularization of the
      normally avascular cornea, a process that involves the vascular endothelial
      growth factor (VEGF) family of proteins. In this report, we targeted the
      proliferating vascular endothelial cells expressing VEGFR-2 in the SK cornea by
      immunization with recombinant Salmonella typhimurium containing a plasmid
      encoding murine VEGFR-2. This form of DNA immunization resulted in diminished
      angiogenesis and delayed development of SK caused by HSV-1 infection and also
      reduced angiogenesis resulting from corneal implantation with rVEGF. CTL
      responses against endothelial cells expressing VEGFR-2 were evident in the VEGFR
      2-immunized group and in vivo CD8+ T cell depletion resulted in the marked
      reduction of the antiangiogenic immune response. These results indicate a role
      for CD8+ T cells in the antiangiogenic effects. Our results may also imply that
      the anti-VEGFR-2 vaccination approach might prove useful to control pathological
      ocular angiogenesis and its consequences.

PMID- 16951378
TI  - First identification of a chemotactic receptor in an invertebrate species:
      structural and functional characterization of Ciona intestinalis C3a receptor.
AB  - In mammals, the bioactive fragment C3a, released from C3 during complement
      activation, is a potent mediator of inflammatory reactions and exerts its
      functional activity through the specific binding to cell surface G protein
      coupled seven-transmembrane receptors. Recently, we demonstrated a Ciona
      intestinalis C3a (CiC3a)-mediated chemotaxis of hemocytes in the deuterostome
      invertebrate Ciona intestinalis and suggested an important role for this molecule
      in inflammatory processes. In the present work, we have cloned and characterized
      the receptor molecule involved in the CiC3a-mediated chemotaxis and studied its
      expression profile. The sequence, encoding a 95,394 Da seven-transmembrane domain
      protein, shows the highest sequence homology with mammalian C3aRs. Northern blot
      analysis revealed that the CiC3aR is expressed abundantly in the heart and neural
      complex and to a lesser extent in the ovaries, hemocytes, and larvae. Three
      polyclonal Abs raised in rabbits against peptides corresponding to CiC3aR regions
      of the first and second extracellular loop and of the third intracellular loop
      react specifically in Western blotting with a single band of 98-102 kDa in
      hemocyte protein extracts. Immunostaining performed on circulating hemocytes with
      the three specific Abs revealed that CiC3aR is constitutively expressed only in
      hyaline and granular amoebocytes. In chemotaxis experiments, the Abs against the
      first and second extracellular loop inhibited directional migration of hemocytes
      toward the synthetic peptide reproducing the CiC3a C-terminal sequence, thus
      providing the compelling evidence that C. intestinalis expresses a functional
      C3aR homologous to the mammalian receptor. These findings further elucidate the
      evolutionary origin of the vertebrate complement-mediated proinflammatory
      process.

PMID- 16951379
TI  - Opposing actions of Stat1 and Stat6 on IL-13-induced up-regulation of early
      growth response-1 and platelet-derived growth factor ligands in pulmonary
      fibroblasts.
AB  - IL-13 is a key cytokine involved in airway remodeling in asthma. We previously
      reported that IL-13 stimulated the mitogenesis of lung fibroblasts via platelet
      derived growth factor (PDGF)-AA. In this report, we show that IL-13 increases
      PDGF-A and PDGF-C mRNA levels through a dual intracellular cascade that requires
      coactivation of Stat6 and Stat1 to impact transcriptional regulation of the early
      growth response (Egr)-1 gene, which then drives PDGF expression. Increased levels
      of PDGF-AA and PDGF-CC protein were observed in vivo in the airways of IL-13
      transgenic mice. IL-13 up-regulated PDGF-A and PDGF-C mRNA levels in lung
      fibroblasts isolated from three different background strains of mice. However, IL
      13-induced PDGF-A and PDGF-C mRNA levels were significantly reduced in Stat6
      deficient (Stat6(-/-)) fibroblasts as compared with wild-type Stat6(+/+)
      fibroblasts. In contrast, IL-13-induced PDGF-A and PDGF-C mRNAs were enhanced in
      Stat1(-/-) fibroblasts as compared with Stat1(+/+) fibroblasts. IL-13 did not up
      regulate PDGF-A or PDGF-C mRNA levels in Egr-1(-/-) fibroblasts. Moreover, IL-13
      did not increase Egr-1 mRNA and protein levels in Stat6(-/-) fibroblasts and yet
      enhanced Egr-1 mRNA and protein levels in Stat1(-/-) fibroblasts. Our findings
      support the hypothesis that Stat6 and Stat1 exert stimulatory and inhibitory
      effects on Egr-1 and PDGF ligand mRNA transcription, respectively. This novel
      mechanism could aid in identifying molecular targets for the treatment of chronic
      airway remodeling and fibrosis in asthma.

PMID- 16951380
TI  - CCR4 participation in Th type 1 (mycobacterial) and Th type 2 (schistosomal)
      anamnestic pulmonary granulomatous responses.
AB  - CCR4 is purported to be a Th type 2 (Th2) cell-biased receptor but its functional
      role is unclear. Recent studies suggest that chemokine receptor expression and
      function are more complex in vivo and raise doubts regarding restricted CCR4
      expression by Th2 cells. To address these issues, we analyzed the role of CCR4 in
      highly polarized models of Th type 1 (Th1) and Th2 cell-mediated pulmonary
      granulomas, respectively, elicited by i.v. challenge of primed mice with either
      mycobacterial purified protein derivative or schistosomal egg Ag-coated beads.
      CCR4 agonists were expressed during both responses, correlating with a shift of
      CCR4+ CD4+ T cells from blood to lungs. CCL22 dominated in draining nodes during
      the Th1 response. Analysis of CD4+ effector T cells revealed CCR4 expression and
      CCR4-mediated chemotaxis by both IFN-gamma and IL-4 producers. Studies of CCR4
      knockout (CCR4(-/-)) mice showed partial impairment of the local type-2 cytokine
      response and surprisingly strong impairment of the Th1 response with abrogated
      IFN-gamma production during secondary but not primary challenge. Adoptive
      transfer indicated CCR4(-/-)CD4+ Th1 cell function was defective but this could
      not be reconstituted with wild-type (CCR4(+/+)) CD4+ T cells indicating
      involvement of another CCR4+ population. Coculture of CCR4(+/+)CD4+ T cells and
      CCR4(-/-) dendritic cells revealed intact IL-2 but impaired IFN-gamma production,
      pointing to a role for CCR4+ dendritic cells in effector cell expression.
      Therefore, CCR4 is not Th2-restricted and was required for sustenance and
      expression of the Th1 effector/memory response to mycobacterial Ags.

PMID- 16951381
TI  - DNA immunization against tissue-restricted antigens enhances tumor immunity after
      allogeneic hemopoietic stem cell transplantation.
AB  - Malignant relapse remains a major problem for recipients of allogeneic
      hemopoietic stem cell transplantation (HSCT). We hypothesized that immunization
      of allogeneic HSCT recipients against tissue-restricted Ags using DNA vaccines
      would decrease the risk of relapse without enhancing graft-vs-host disease
      (GVHD). Using the mouse B16 melanoma model, we found that post-HSCT DNA
      immunization against a single tumor Ag induces tumor rejection that is
      significantly greater than HSCT alone in a T cell-depleted MHC-matched minor Ag
      mismatched allogeneic HSCT model (LP --> B6). In treatment models, post-HSCT DNA
      immunization provides significantly greater overall survival than the vaccine
      alone. Donor leukocyte infusion further enhances tumor-free survival, including
      in treatment models. There was no GVHD in HSCT recipients treated with DNA
      vaccination and donor leukocyte infusion. Further analysis demonstrated that
      these effects are dependent on CD8+ T cells of donor origin that recognize
      multiple epitopes. These results demonstrate that DNA immunization against tissue
      restricted Ags after allogeneic T cell-depleted HSCT can induce potent antitumor
      effects without causing GVHD.

PMID- 16951382
TI  - Killing of normal melanocytes, combined with heat shock protein 70 and CD40L
      expression, cures large established melanomas.
AB  - Previously, we showed that nine intradermal injections of a plasmid in which the
      HSVtk suicide gene is expressed from a melanocyte-specific promoter (Tyr-HSVtk),
      combined with a plasmid expressing heat shock protein 70 (CMV-hsp70), along with
      systemic ganciclovir, kills normal melanocytes and raises a CD8+ T cell response
      that is potent enough to eradicate small, 3-day established B16 tumors. We show
      in this study that, in that regimen, hsp70 acts as a potent immune adjuvant
      through TLR-4 signaling and local induction of TNF-alpha. hsp70 is required for
      migration of APC resident in the skin to the draining lymph nodes to present Ags,
      derived from the killing of normal melanocytes, to naive T cells. The addition of
      a plasmid expressing CD40L increased therapeutic efficacy, such that only six
      plasmid injections were now required to cure large, 9-day established tumors.
      Generation of potent immunological memory against rechallenge in cured mice
      accompanied these therapeutic gains, as did induction of aggressive autoimmune
      symptoms. Expression of CD40L, along with hsp70, increased both the frequency and
      activity of T cells activated against melanocyte-derived Ags. In this way,
      addition of CD40L to the hsp70-induced inflammatory killing of melanocytes can be
      used to cure large established tumors and to confer immunological memory against
      tumor cells, although a concomitant increase in autoimmune sequelae also is
      produced.

PMID- 16951383
TI  - Gliadin-specific type 1 regulatory T cells from the intestinal mucosa of treated
      celiac patients inhibit pathogenic T cells.
AB  - Celiac disease (CD) results from a permanent intolerance to dietary gluten and is
      due to a massive T cell-mediated immune response to gliadin, the main component
      of gluten. In this disease, the regulation of immune responses to dietary gliadin
      is altered. Herein, we investigated whether IL-10 could modulate anti-gliadin
      immune responses and whether gliadin-specific type 1 regulatory T (Tr1) cells
      could be isolated from the intestinal mucosa of CD patients in remission. Short
      term T cell lines were generated from jejunal biopsies, either freshly processed
      or cultured ex vivo with gliadin in the presence or absence of IL-10. Ex vivo
      stimulation of CD biopsies with gliadin in the presence of IL-10 resulted in
      suppression of Ag-specific proliferation and cytokine production, indicating that
      pathogenic T cells are susceptible to IL-10-mediated immune regulation. T cell
      clones generated from intestinal T cell lines were tested for gliadin specificity
      by cytokine production and proliferative responses. The majority of gliadin
      specific T cell clones had a Th0 cytokine production profile with secretion of IL
      2, IL-4, IFN-gamma, and IL-10 and proliferated in response to gliadin. Tr1 cell
      clones were also isolated. These Tr1 cells were anergic, restricted by DQ2 (a CD
      associated HLA), and produced IL-10 and IFN-gamma, but little or no IL-2 or IL-4
      upon activation with gliadin or polyclonal stimuli. Importantly, gliadin-specific
      Tr1 cell clones suppressed proliferation of pathogenic Th0 cells. In conclusion,
      dietary Ag-specific Tr1 cells are present in the human intestinal mucosa, and
      strategies to boost their numbers and/or function may offer new therapeutic
      opportunities to restore gut homeostasis.

PMID- 16951384
TI  - Antibody targeting to a class I MHC-peptide epitope promotes tumor cell death.
AB  - Therapeutic mAbs that target tumor-associated Ags on the surface of malignant
      cells have proven to be an effective and specific option for the treatment of
      certain cancers. However, many of these protein markers of carcinogenesis are not
      expressed on the cells' surface. Instead these tumor-associated Ags are processed
      into peptides that are presented at the cell surface, in the context of MHC class
      I molecules, where they become targets for T cells. To tap this vast source of
      tumor Ags, we generated a murine IgG2a mAb, 3.2G1, endowed with TCR-like binding
      specificity for peptide-HLA-A*0201 (HLA-A2) complex and designated this class of
      Ab as TCR mimics (TCRm). The 3.2G1 TCRm recognizes the GVL peptide (GVLPALPQV)
      from human chorionic gonadotropin beta presented by the peptide-HLA-A*0201
      complex. When used in immunofluorescent staining reactions using GVL peptide
      loaded T2 cells, the 3.2G1 TCRm specifically stained the cells in a peptide and
      Ab concentration-dependent manner. Staining intensity correlated with the extent
      of cell lysis by complement-dependent cytotoxicity (CDC), and a peptide
      concentration-dependent threshold level existed for the CDC reaction. Staining of
      human tumor lines demonstrated that 3.2G1 TCRm was able to recognize endogenously
      processed peptide and that the breast cancer cell line MDA-MB-231 highly
      expressed the target epitope. The 3.2G1 TCRm-mediated CDC and Ab-dependent
      cellular cytotoxicity of a human breast carcinoma line in vitro and inhibited in
      vivo tumor implantation and growth in nude mice. These results provide validation
      for the development of novel TCRm therapeutic reagents that specifically target
      and kill tumors via recognition and binding to MHC-peptide epitopes.

PMID- 16951385
TI  - Innate immunity in multiple sclerosis: myeloid dendritic cells in secondary
      progressive multiple sclerosis are activated and drive a proinflammatory immune
      response.
AB  - Multiple sclerosis (MS) is postulated to be a T cell-mediated autoimmune disease
      characterized clinically by a relapsing-remitting (RR) stage followed by a
      secondary progressive (SP) phase. The progressive phase is felt to be secondary
      to neuronal degenerative changes triggered by inflammation. The status of the
      innate immune system and its relationship to the stages of MS is not well
      understood. Dendritic cells (DCs) are professional APCs that are central cells of
      the innate immune system and have the unique capacity to induce primary immune
      responses. We investigated circulating myeloid DCs isolated directly from the
      blood to determine whether there were abnormalities in myeloid DCs in MS and
      whether they were related to disease stage. We found that SP-MS subjects had an
      increased percentage of DCs expressing CD80, a decreased percentage expressing PD
      L1, and an increased percentage producing IL-12 and TNF-alpha compared with RR-MS
      or controls. A higher percentage of DCs from both RR and SP-MS patients expressed
      CD40 compared with controls. We then investigated the polarization effect of DCs
      from MS patients on naive T cells taken from cord blood using a MLR assay.
      Whereas DCs from RR-MS induced higher levels of Th1 (IFN-gamma, TNF-alpha) and
      Th2 (IL-4, IL-13) cytokines compared with controls, DCs from SP-MS only induced a
      polarized Th1 response. These results demonstrate abnormalities of DCs in MS and
      may explain the immunologic basis for the different stages and clinical patterns
      of MS.

PMID- 16951386
TI  - Increased frequencies of cochlin-specific T cells in patients with autoimmune
      sensorineural hearing loss.
AB  - Autoimmune sensorineural hearing loss (ASNHL) is the most common cause of sudden
      hearing loss in adults. Although autoimmune etiopathogenic events have long been
      suspected in ASNHL, inner ear-specific Ags capable of targeting T cell
      autoreactivity have not been identified in ASNHL. In this study, we show by
      ELISPOT analysis that compared with normal hearing age- and sex-matched control
      subjects, ASNHL patients have significantly higher frequencies of circulating T
      cells producing either IFN-gamma (p = 0.0001) or IL-5 (p = 0.03) in response to
      recombinant human cochlin, the most abundant inner ear protein. In some patients,
      cochlin responsiveness involved both CD4+ and CD8+ T cells whereas other patients
      showed cochlin responsiveness confined to CD8+ T cells. ASNHL patients also
      showed significantly elevated cochlin-specific serum Ab titers compared with both
      normal hearing age- and sex-matched control subjects and patients with noise-
      and/or age-related hearing loss (p < 0.05 at all dilutions tested through
      1/2048). Our study is the first to show T cell responsiveness to an inner ear
      specific protein in ASNHL patients, and implicates cochlin as a prominent target
      Ag for mediating autoimmune inner ear inflammation and hearing loss.

PMID- 16951387
TI  - Mannose-binding lectin contributes to the severity of Guillain-Barre syndrome.
AB  - In Guillain-Barre syndrome (GBS), complement activation plays a crucial role in
      the induction and extent of the postinfectious immune-mediated peripheral nerve
      damage. Mannose-binding lectin (MBL) activates the complement system via the
      lectin pathway after recognition of repetitive sugar groups on pathogens. We
      investigated whether the MBL2 genotype, serum MBL level, and MBL complex activity
      are associated with the development and severity of GBS. Single nucleotide
      polymorphisms in the promoter region (-550 H/L and -221 X/Y) and exon 1 (A/O) of
      the MBL2 gene were determined in 271 GBS patients and 212 healthy controls. The
      frequencies of the H allele, HY promoter haplotype, and HYA haplotype, which are
      related to high MBL activity, were all increased in GBS patients compared with
      healthy controls (p < or = 0.03), particularly in severely affected GBS patients
      (MRC-sum score < 40) (p < or = 0.02). Severe weakness was also associated with
      high MBL concentrations and MBL complex activity in sera from GBS patients (p <
      0.01). The MBL2 B allele was associated with functional deficiency and relatively
      mild weakness. These results support the hypothesis that complement activation
      mediated by MBL contributes to the extent of nerve damage in GBS, which is
      codetermined by the MBL2 haplotype.

PMID- 16951388
TI  - CD45neg but not CD45pos human myeloma cells are sensitive to the inhibition of
      IGF-1 signaling by a murine anti-IGF-1R monoclonal antibody, mAVE1642.
AB  - Insulin-like growth factor 1 (IGF-1) is a well-known growth factor for myeloma
      cells. Thus, therapeutic strategies targeting IGF-1R have been proposed for
      multiple myeloma treatment. In this study, we investigated the effect of the
      antagonistic anti-IGF-1R murineAVE1642 Ab (mAVE1642). We show that mAVE1642
      selectively inhibits IGF-1R but not insulin signaling in human myeloma cell
      lines. Since we have previously shown the functional relevance of CD45 expression
      in the growth of myeloma cells and the association of CD45-negative (CD45neg)
      status with a less favorable clinical outcome, both CD45-positive (CD45pos) and
      CD45neg myeloma cell lines were selected for our study. We found that mAVE1642
      strongly inhibits the growth of CD45neg myeloma cell lines, leading to a G1
      growth arrest, whereas it has almost no effect on the growth of CD45pos myeloma
      cell lines. Furthermore, mAVE1642 binding induced a significant reduction of IGF
      1R expression. We next demonstrated that the overexpression of IGF-1R in the
      CD45pos myeloma cell line increased Akt phosphorylation but was not sufficient to
      sensitize these cells to mAVE1642. In contrast, we generated a stable CD45
      silencing XG-1 cell line and showed that it became sensitive to mAVE1642. Thus,
      for the first time, we provided direct evidence that the expression of CD45
      renders cells resistant to mAVE1642. Taken together, these results support that
      therapy directed against IGF-1R can be beneficial in treating CD45neg patients.

PMID- 16951389
TI  - Adjuvant therapy with trastuzumab for HER-2/neu-positive breast cancer.
AB  - Breast cancer is the most common cancer in women in the U.S. and western Europe.
      Amplification of the her-2/neu gene occurs in approximately 25% of invasive
      ductal carcinomas of the breast. In experimental models, transfection of the her
      2/neu gene results in transformation of mammary epithelial cells. In human breast
      cancer, amplification of the her-2/neu gene results in protein over expression
      and poor prognosis. Patients whose tumors have her-2/neu gene amplification have
      a shorter disease-free survival time than patients whose tumors exhibit a normal
      her-2/neu gene copy number. her-2/ neu gene amplification identifies a
      biologically unique subset of aggressive breast tumors that are sensitive to
      growth inhibition and apoptosis induced by anti-HER-2/neu-targeted therapies. The
      first HER-2/neu-targeted approach to reach the clinic was trastuzumab, a
      humanized monoclonal antibody directed against the extracellular domain of the
      HER-2/neu protein. Trastuzumab therapy prolongs the survival of patients with
      metastatic HER-2/neu-overexpressing breast cancer when combined with chemotherapy
      and has recently been demonstrated to lead to dramatic improvements in disease
      free survival when used in the adjuvant therapy setting in combination with or
      following chemotherapy. However, potential cardiotoxicity requires careful
      patient selection. Here, we review the recently completed clinical trials of
      adjuvant trastuzumab in the adjuvant setting. HER-2/neu testing, patient
      selection, cardiotoxicity, duration of therapy, and directions for future
      research are discussed.

PMID- 16951390
TI  - Molecular classification of breast cancer: limitations and potential.
AB  - Reverse transcription polymerase chain reaction and DNA microarrays are
      increasingly used in the clinic and in clinical research as prognostic or
      predictive tests. Results from these tests led to novel risk stratification
      methods and to new molecular classification of breast cancer. Some of these tools
      already complement existing diagnostic tests and can aid medical decision making
      in some situations. Better understanding of the molecular classes of breast
      cancer, independent of their prognostic and predictive values, may also lead to
      new biological insights and eventually to better therapies that are directed
      toward particular molecular subsets. However, there is substantially less
      experience with these emerging technologies than with the more established
      methods, the accuracy of which is often overestimated. This review discusses some
      of the limitations and strengths of current gene expression-based molecular
      classification of breast cancer. To provide context for this discussion, we also
      briefly examine the performance of estrogen receptor immunohistochemistry, which
      represents an essential part of the routine diagnostic workup for all breast
      cancer patients.

PMID- 16951391
TI  - Chromogenic in situ hybridization to detect HER-2/neu gene amplification in
      histological and ThinPrep-processed breast cancer fine-needle aspirates: a
      sensitive and practical method in the trastuzumab era.
AB  - The increasing evidence of trastuzumab efficacy in breast cancer (BC) patients
      means that an accurate and reproducible evaluation of HER-2 statusis of paramount
      importance in histological and in cytological samples. Currently, the two main
      methods used to analyze HER-2 amplification or overexpression are fluorescence in
      situ hybridization (FISH) and immunohistochemistry (IHC). Although the two
      methods are strongly correlated for histological tissue, the evaluation of tumor
      morphology through FISH may be difficult and fluorescence fades quickly. These
      limitations can be overcome by chromogenic in situ hybridization (CISH), which
      can visualize the amplification product along with morphological features. In
      view of this, in the present study, we analyzed the usefulness of CISH on
      formalin-fixed, paraffin-embedded (FFPE) BC specimens and investigated whether
      CISH can be a valid technique in the determination of HER-2 status for fine
      needle aspirates (FNAs) processed by liquid-based cytology. The results we
      obtained in a retrospective series of 111 FFPE BC specimens demonstrated good
      concordance between CISH and IHC and between CISH and FISH. The former
      concordance was comparable with that observed between FISH and IHC. When CISH was
      applied to a prospective series of 53 FNAs, from surgically removed BC, our data
      showed evidence of a higher concordance of results between liquid-based cytology
      and the companion FFPE tissues using CISH rather than HercepTesttrade mark.
      Therefore, CISH analysis, which is avaluable and reproducible alternative to FISH
      for selecting breast cancer patients for trastuzumab therapy, can lower false
      positive immunocytochemistry findings in ThinPrep-processed FNAs.

PMID- 16951392
TI  - Thymoma: benign appearance, malignant potential.
AB  - Thymoma is a rare tumor with a largely indolent growth pattern. It does, however,
      have malignant potential as a result of its ability to invade locally and
      metastasize regionally. Often associated with a number of immune- and nonimmune
      mediated paraneoplastic syndromes, patient outcomes are directly related to stage
      of disease and the ability to achieve a complete surgical resection. Surgery is
      the mainstay of treatment, with adjuvant radiation recommended for invasive
      thymoma. Sensitive to both chemotherapy and radiation, durable responses are
      achievable in incompletely resected and inoperable patients. We present two cases
      of thymoma followed by a general discussion with an emphasis on treatment for
      both early and advanced-stage disease.

PMID- 16951393
TI  - Role of minimally invasive surgery in gynecologic cancers.
AB  - The role of minimally invasive surgery in the management of gynecologic cancers
      continues to expand. Radical vaginal trachelectomy with laparoscopic pelvic
      lymphadenectomy has emerged as a safe, reasonable option for women with early
      stage cervical cancer desiring fertility preservation. Similarly,
      laparoscopically assisted radical vaginal hysterectomy has been systematically
      described, is feasible, and can be offered to women with early-stage cervical
      cancer who do not desire future childbearing. In the treatment of early-stage
      endometrial cancer, the surgical approach of laparoscopic hysterectomy,
      peritoneal washings, and pelvic and para-aortic lymph node dissection, with or
      without an omentectomy, is being compared with the same surgery performed via
      laparotomy in the cooperative Gynecologic Oncology Group LAP 2 study, which has
      completed accrual, and appears to be a reasonable surgical option. In ovarian
      cancer, minimally invasive surgery has been incorporated to manage early-stage,
      advanced-stage, and recurrent disease, as well as second-look procedures. Hand
      assisted laparoscopy has also recently been described in managing larger volume
      primary and recurrent gynecologic cancers. Extraperitoneal laparoscopy for para
      aortic and pelvic lymph node dissections has been shown to yield adequate nodal
      counts and to be safe and feasible in the management of gynecologic cancers.

PMID- 16951394
TI  - Fallopian tube carcinoma: a review.
AB  - PURPOSE: Primary fallopian tube carcinoma (PFTC) is a rare tumor that
      histologically and clinically resembles epithelial ovarian cancer (EOC). The
      purpose of this study is to review the current available literature data on PFTC.
      PATIENTS AND RESULTS: Early clinical manifestation and prompt investigation often
      lead to diagnosis at an early stage of disease. However, the diagnosis of PFTC is
      rarely considered preoperatively and is usually first appreciated by the
      pathologist. Surgical staging/management and the use of chemotherapy follow the
      concepts used in epithelial ovarian cancer (EOC). In contrast to EOC is the
      importance of early lymphatic spread in this disease. The earlier diagnosis of
      PFTC leads to an apparent better survival compared with EOC. However, as with
      EOC, stage and residual tumor are the most important prognostic variables.
      CONCLUSION: Until more extensive clinical research has been performed, ovarian
      carcinoma management principles should be used in clinical practice.

PMID- 16951395
TI  - What is the current state-of-the-art imaging for detection and staging of
      cholangiocarcinoma?
AB  - Cholangiocarcinoma is an adenocarcinoma that arises from the bile duct epithelium
      and is the second most common primary hepatobiliary cancer, after hepatocellular
      cancer, with approximately 2,500 cases annually in the U.S. However,
      cholangiocarcinoma remains a relatively rare disease, accounting for <2% of all
      human malignancies. Although the entire biliary tree is potentially at risk,
      tumors involving the biliary confluence or the right or left hepatic ducts (hilar
      cholangiocarcinoma) are most common and account for 40%-60% of all cases. Most
      patients present with advanced disease that is not amenable to surgical
      treatment. The median survival time for patients with intrahepatic
      cholangiocarcinoma without involvement of the hilum varies among centers from 18
      30 months. The median survival time for patients with perihilar
      cholangiocarcinoma is slightly less, varying from 12-24 months. Despite the
      overall poor prognosis, survival after surgical treatment of hilar
      cholangiocarcinoma has improved during the past 10-15 years. This review
      highlights the imaging features of cholangiocarcinoma, with particular emphasis
      on the imaging techniques that can best assess tumor resectability and guide the
      surgeon regarding the potential extent of resection required in operable
      candidates.

PMID- 16951396
TI  - Disseminated intravascular B-cell lymphoma: clinicopathological features and
      outcome of three cases treated with anthracycline-based immunochemotherapy.
AB  - The purpose of this study was to evaluate the use of combination anthracycline
      based immunochemotherapy in intravascular lymphoma (IVL). This is an extremely
      rare, disseminated, and aggressive extranodal CD20(+) non-Hodgkin's lymphoma
      (NHL) with poor outcome following anthracycline-based chemotherapy. From a
      population of 700 newly diagnosed patients with NHL who were registered and
      followed up at our unit between 1990 and 2005, three cases (0.4%) have been
      classified as IVL. Among the patients, there were two men and one woman, with a
      median age of 52 years. We have assessed the clinicopathological characteristics,
      response to therapy, and outcome. All patients presented with systemic symptoms
      and disseminated disease. All patients received anthracycline-based chemotherapy
      in combination with the anti-CD20 monoclonal antibody rituximab
      (immunochemotherapy). Complete remission was achieved in all three patients, and
      currently all remain progression free with a follow-up of 24-45 months. In
      conclusion, anthracycline-based immunochemotherapy induces durable remissions in
      patients with IVL, an ultimately fatal disease, suggesting that the clinical
      course of this disease may be altered with immunochemotherapy.

PMID- 16951397
TI  - Advances in the therapy of chronic idiopathic myelofibrosis.
AB  - The molecular basis of chronic idiopathic myelofibrosis (CIMF) has remained
      elusive, thus hampering the development of effective targeted therapies. However,
      significant progress regarding the molecular mechanisms involved in the
      pathogenes is of this disease has been made in recent years that will likely
      provide ample opportunity for the investigation of novel therapeutic approaches.
      At the fore front of these advances is the discovery that 35%-55% of patients
      with CIMF harbor mutations in the Janus kinase 2 tyrosine kinase gene. Until very
      recently, the management of patients with CIMF involved the use of supportive
      measures, including growth factors, transfusions, or interferon, and the
      administration of cyto-reductive agents, such as hydroxyurea and anagrelide.
      However, several trials have demonstrated the efficacy of antiangiogenic agents
      alone or in combination with corticosteroids. In addition, the use of reduced
      intensity conditioning allogeneic stem cell transplantation has resulted in
      prolonged survival and lower transplant-related mortality.

PMID- 16951398
TI  - Prophylaxis of irinotecan-induced diarrhea with neomycin and potential role for
      UGT1A1*28 genotype screening: a double-blind, randomized, placebo-controlled
      study.
AB  - OBJECTIVE: Delayed-type diarrhea is a common side effect of irinotecan and is
      associated with a bacterial-mediated formation of the active irinotecan
      metabolite SN-38 from its glucuronide conjugate in the intestine. Based on a
      pilot study, we hypothesized that concomitant administration of the antibiotic
      neomycin would diminish exposure of the gut to SN-38 and ameliorate the incidence
      and severity of diarrhea. PATIENTS AND METHODS: Patients were treated with
      irinotecan in a multicenter, double-blind, randomized, placebo-controlled trial.
      Eligible patients received irinotecan (350 mg/m(2) once every 3 weeks) combined
      with neomycin (660 mg three times daily for three consecutive days, starting 2
      days before chemotherapy) or combined with placebo. Blood samples were obtained
      for additional pharmacokinetic and pharmacogenetic analyses. RESULTS: Sixty-two
      patients were evaluable for the toxicity analysis. Baseline patient
      characteristics, systemic SN-38 exposure, and UGT1A1*28 genotype status (i.e., an
      additional TA repeat in the promoter region of uridine diphosphate
      glucuronosyltransferase isoform 1A1) were similar in both arms. Although
      distribution, severity, and duration of delayed-type diarrhea did not differ
      significantly between arms, grade 3 diarrhea tended to be less frequent in the
      neomycin arm. The presence of at least one UGT1A1*28 allele was strongly related
      to the incidence of grade 2-3 diarrhea. In the neomycin arm, grade 2 nausea was
      significantly more common. CONCLUSION: Our results do not suggest a major role
      for neomycin as prophylaxis for irinotecan-induced delayed-type diarrhea. It is
      suggested that the UGT1A1*28 genotype status could be used as a screening tool
      for a priori prevention of irinotecan-induced delayed-type diarrhea.

PMID- 16951399
TI  - Prognosis of lymphomatoid papulosis.

PMID- 16951402
TI  - Dietary flavonoids with a catechol structure increase alpha-tocopherol in rats
      and protect the vitamin from oxidation in vitro.
AB  - To identify dietary phenolic compounds capable of improving vitamin E status,
      male Sprague-Dawley rats were fed for 4 weeks either a basal diet (control) with
      2 g/kg cholesterol and an adequate content of vitamin E or the basal diet
      fortified with quercetin (Q), (-)-epicatechin (EC), or (+)-catechin (C) at
      concentrations of 2 g/kg. All three catechol derivatives substantially increased
      concentrations of alpha-tocopherol (alpha-T) in blood plasma and liver. To study
      potential mechanisms underlying the observed increase of alpha-T, the capacities
      of the flavonoids to i) protect alpha-T from oxidation in LDL exposed to peroxyl
      radicals, ii) reduce alpha-tocopheroxyl radicals (alpha-T (.) ) in SDS micelles,
      and iii) inhibit the metabolism of tocopherols in HepG2 cells were determined.
      All flavonoids protected alpha-T from oxidation in human LDL ex vivo and dose
      dependently reduced the concentrations of alpha-T (.) . None of the test
      compounds affected vitamin E metabolism in the hepatocyte cultures. In
      conclusion, fortification of the diet of Sprague-Dawley rats with Q, EC, or C
      considerably improved their vitamin E status. The underlying mechanism does not
      appear to involve vitamin E metabolism but may involve direct quenching of free
      radicals or reduction of the alpha-T (.) by the flavonoids.

PMID- 16951401
TI  - Studying apolipoprotein turnover with stable isotope tracers: correct analysis is
      by modeling enrichments.
AB  - Lipoprotein kinetic parameters are determined from mass spectrometry data after
      administering mass isotopes of amino acids, which label proteins endogenously.
      The standard procedure is to model the isotopic content of the labeled precursor
      amino acid and of proteins of interest as tracer-to-tracee ratio (TTR). It is
      shown here that even though the administered tracer alters amino acid mass and
      turnover, apolipoprotein synthesis is unaltered and hence the apolipoprotein
      system is in a steady state, with the total (labeled plus unlabeled) masses and
      fluxes remaining constant. The correct model formulation for apolipoprotein
      kinetics is shown to be in terms of tracer enrichment, not of TTR. The needed
      mathematical equations are derived. A theoretical error analysis is carried out
      to calculate the magnitude of error in published results using TTR modeling. It
      is shown that TTR modeling leads to a consistent underestimation of the
      fractional synthetic rate. In constant-infusion studies, the bias error percent
      is shown to equal approximately the plateau enrichment, generally <10%. It is
      shown that, in bolus studies, the underestimation error can be larger. Thus, for
      mass isotope studies with endogenous tracers, apolipoproteins are in a steady
      state and the data should be fitted by modeling enrichments.

PMID- 16951403
TI  - Necessary role for the Lag1p motif in (dihydro)ceramide synthase activity.
AB  - Lag1 (longevity assurance gene 1) homologues, a family of transmembrane proteins
      found in all eukaryotes, have been shown to be necessary for (dihydro)ceramide
      synthesis. All Lag1 homologues contain a highly conserved stretch of 52 amino
      acids known as the Lag1p motif. However, the functional significance of the
      conserved Lag1p motif for (dihydro)ceramide synthesis is currently unknown. In
      this work, we have investigated the function of the motif by introducing eight
      point mutations in the Lag1p motif of the mouse LASS1 (longevity assurance
      homologue 1 of yeast Lag1). The (dihydro)ceramide synthase activity of the
      mutants was tested using microsomes in HeLa cells and in vitro. Six of the
      mutations resulted in loss of activity in cells and in vitro. In addition, our
      results showed that C18:0 fatty acid CoA (but not cis-C18:1 fatty acid CoAs) are
      substrates for LASS1 and that LASS1 in HeLa cells is sensitive to fumonisin B1,
      an in vitro inhibitor of (dihydro)ceramide synthase. Moreover, we mutated the
      Lag1p motif of another Lag homologue, human LASS5. The amino acid substitutions
      in the human LASS5 were the same as in mouse LASS1, and had the same effect on
      the in vitro activity of LASS5, suggesting the Lag1p motif appears to be
      essential for the enzyme activity of all Lag1 homologues.

PMID- 16951404
TI  - The human OCT-4 isoforms differ in their ability to confer self-renewal.
AB  - OCT-4 transcription factors play an important role in maintaining the pluripotent
      state of embryonic stem cells and may prevent expression of genes activated
      during differentiation. Human OCT-4 isoform mRNAs encode proteins that have
      identical POU DNA binding domains and C-terminal domains but differ in their N
      terminal domains. We report here the cloning and characterization of the human
      OCT-4B isoform. Human OCT-4B cDNA encodes a 265-amino acid protein with a
      predicted molecular mass of 30 kDa. Embryonic stem (ES) cell-based
      complementation assays using ZHBTc4 ES cells showed that unlike human OCT-4A, OCT
      4B cannot sustain ES cell self-renewal. In addition, OCT-4B does not bind to a
      probe carrying the OCT-4 consensus binding sequence, and we demonstrate that two
      separate regions of its N-terminal domain are responsible for inhibiting DNA
      binding. We also demonstrate that OCT-4B is mainly localized to the cytoplasm.
      Overexpression of OCT-4B did not activate transcription from OCT-4-dependent
      promoters, although OCT-4A did as reported previously. Furthermore,
      transcriptional activation by human OCT-4A was not inhibited by co-expression of
      OCT-4B. Taken together, these data suggest that the DNA binding, transactivation,
      and abilities to confer self-renewal of the human OCT-4 isoforms differ.

PMID- 16951405
TI  - DAB1 and Reelin effects on amyloid precursor protein and ApoE receptor 2
      trafficking and processing.
AB  - Numerous cytoplasmic adaptor proteins, including JIP1, FE65, and X11alpha, affect
      amyloid precursor protein (APP) processing and Abeta production. Dab1 is another
      adaptor protein that interacts with APP as well as with members of the apoE
      receptor family. We examined the effect of Dab1 on APP and apoEr2 processing in
      transfected cells and primary neurons. Dab1 interacted with APP and apoEr2 and
      increased levels of their secreted extracellular domains and their cytoplasmic C
      terminal fragments. These effects depended on the NPXY domains of APP and apoEr2
      and on the phosphotyrosine binding domain of Dab1 but did not depend on
      phosphorylation of Dab1. Dab1 decreased the levels of APP beta-C-terminal
      fragment and secreted Abeta. Full-length Dab1 or its phosphotyrosine binding
      domain alone increased surface levels of APP, as determined by surface protein
      biotinylation and live cell staining. A ligand for apoEr2, the extracellular
      matrix protein Reelin, significantly increased the interaction of apoEr2 with
      Dab1. Surprisingly, we also found that Reelin treatment significantly increased
      the interaction of APP and Dab1. Moreover, Reelin treatment increased cleavage of
      APP and apoEr2 and decreased production of the beta-C-terminal fragment of APP
      and Abeta. Together, these data suggest that Dab1 alters trafficking and
      processing of APP and apoEr2, and this effect is influenced by extracellular
      ligands.

PMID- 16951406
TI  - Eukaryotic initiation factor 2alpha-independent pathway of stress granule
      induction by the natural product pateamine A.
AB  - Stress granules are aggregates of small ribosomal subunits, mRNA, and numerous
      associated RNA-binding proteins that include several translation initiation
      factors. Stress granule assembly occurs in the cytoplasm of higher eukaryotic
      cells under a wide variety of stress conditions, including heat shock, UV
      irradiation, hypoxia, and exposure to arsenite. Thus far, a unifying principle of
      eukaryotic initiation factor 2alpha phosphorylation prior to stress granule
      formation has been observed from the majority of experimental evidence. Pateamine
      A, a natural product isolated from marine sponge, was recently reported to
      inhibit eukaryotic translation initiation and induce the formation of stress
      granules. In this report, the protein composition and fundamental progression of
      stress granule formation and disassembly induced by pateamine A was found to be
      similar to that for arsenite. However, pateamine A-induced stress granules were
      more stable and less prone to disassembly than those formed in the presence of
      arsenite. Most significantly, pateamine A induced stress granules independent of
      eukaryotic initiation factor 2alpha phosphorylation, suggesting an alternative
      mechanism of formation from that previously described for other cellular
      stresses. Taking into account the known inhibitory effect of pateamine A on
      eukaryotic translation initiation, a model is proposed to account for the
      induction of stress granules by pateamine A as well as other stress conditions
      through perturbation of any steps prior to the rejoining of the 60S ribosomal
      subunit during the entire translation initiation process.

PMID- 16951407
TI  - Spy1 expression prevents normal cellular responses to DNA damage: inhibition of
      apoptosis and checkpoint activation.
AB  - Spy1 is the originally identified member of the Speedy/Ringo family of vertebrate
      cell cycle regulators, which can control cell proliferation and survival through
      the atypical activation of cyclin-dependent kinases. Here we report a role for
      Spy1 in apoptosis and checkpoint activation in response to UV irradiation. Using
      an inducible system allowing for regulated expression of Spy1, we show that Spy1
      expression prevents activation of caspase-3 and suppresses apoptosis in response
      to UV irradiation. Spy1 expression also allows for UV irradiation-resistant DNA
      synthesis and permits cells to progress into mitosis, as demonstrated by
      phosphorylation on histone H3, indicating that Spy1 expression can inhibit the S
      phase/replication and G2/M checkpoints. We demonstrate that Spy1 expression
      inhibits phosphorylation of Chk1, RPA, and histone H2A.X, which may directly
      contribute to the decrease in apoptosis and checkpoint bypass. Furthermore,
      mutation of the conserved Speedy/Ringo box, known to mediate interaction with
      CDK2, abrogates the ability of Spy1 to inhibit apoptosis and the phosphorylation
      of Chk1 and RPA. The data presented indicate that Spy1 expression allows cells to
      evade checkpoints and apoptosis and suggest that Spy1 regulation of CDK2 is
      important for the response to DNA damage.

PMID- 16951408
TI  - Pain sensitivity and fMRI pain-related brain activity in Alzheimer's disease.
AB  - People with Alzheimer's disease are administered fewer analgesics and report less
      clinical pain than cognitively intact peers with similar painful diseases or
      injuries, prompting speculation about the likely impact of neurodegeneration on
      central pain processing. The present study measured pain ratings and functional
      MRI (fMRI) brain responses following mechanical pressure simulation in 14
      patients with Alzheimer's disease and 15 age-matched controls. Contrary to the
      prevailing hypothesis that this disease is likely to differentially reduce
      emotional responses to pain, we show that activity in both medial and lateral
      pain pathways is preserved. Moderate pain was evoked with similar stimuli in both
      groups, and was associated with a common network of pain-related activity
      incorporating cingulate, insula and somatosensory cortices. Between-group
      analyses showed no evidence of diminished pain-related activity in Alzheimer's
      disease patients compared with controls. In fact, compared with controls,
      patients showed greater amplitude and duration of pain-related activity in
      sensory, affective and cognitive processing regions consistent with sustained
      attention to the noxious stimulus. The results of this study show that pain
      perception and processing are not diminished in Alzheimer's disease, thereby
      raising concerns about the current inadequate treatment of pain in this highly
      dependent and vulnerable patient group.

PMID- 16951409
TI  - Magnetization transfer MRI metrics predict the accumulation of disability 8 years
      later in patients with multiple sclerosis.
AB  - In multiple sclerosis, the relationship between conventional MRI findings and the
      clinical evolution of the disease is weak. Magnetization transfer (MT) MRI can
      provide markers reflecting the more disabling features of multiple sclerosis
      pathology. The aim of the present study was to assess the value of MT MRI
      quantities and their short-term changes in predicting the long-term accumulation
      of disability in multiple sclerosis patients. Conventional and MT MRI scans of
      the brain were obtained at baseline and after 12 months in 73 patients, who were
      followed prospectively with clinical visits for a median period of 8 years. At
      baseline and at 12 months, T2-hyperintense and T1-hypointense lesion volume,
      normalized brain volume [with grey (GM) and white matter (WM) fractions] and
      average lesion MT ratio (MTR) were measured. At the two time points, metrics
      derived from the MTR histograms of the whole-brain parenchyma, GM and normal
      appearing WM were also computed. A multivariate analysis, adjusted for follow-up
      duration, was performed to establish which variables were significant predictors
      of long-term neurological deterioration. At the end of follow-up, 44 patients
      (60%) showed a significant disability worsening. A multivariable model included
      baseline GM MTR histogram peak height [P = 0.029, odds ratio (OR) = 0.97], and
      average lesion MTR percentage change after 12 months (P = 0.016, OR = 0.88) as
      independent predictors of disability worsening at 8 years (r2 = 0.28). The
      discriminating ability of such a model in predicting the individual patients'
      outcome was 66%. MT MRI provides useful prognostic markers for the prediction of
      the long-term evolution of multiple sclerosis. This study also suggests that GM
      damage is one of the key factors associated with disability accumulation in this
      'white matter' condition.

PMID- 16951410
TI  - Carbamazepine-resistance in the epileptic dentate gyrus of human hippocampal
      slices.
AB  - Overexpression of drug efflux pumps at the blood brain barrier (BBB) has been
      suggested to be one important factor contributing to drug resistance in epilepsy.
      This would imply that resected brain tissue of drug-resistant patients is drug
      sensitive in absence of the BBB. Here we studied the effects of carbamazepine
      (CBZ) at therapeutically relevant concentration on epileptiform activity
      electrophysiologically recorded in acute hippocampal slices of patients with
      mesial temporal lobe epilepsy (MTLE; 28 patients, 49 slices) or extra-hippocampal
      tumours (tumour; 6 patients, 11 slices). Epileptiform activity was induced by
      hilar stimulation (0.067 Hz) during elevation of extracellular potassium
      concentration ([K(+)](o)) and remained self-sustained in presence of 10-12 mM
      [K(+)](o). Quantitative analysis of data revealed that epileptiform activity in
      tissue of tumour-patients was predominantly suppressed by CBZ, indicating that
      the 'epilepsy model' used is CBZ-sensitive. In contrast, epileptiform activity in
      tissue of drug-resistant MTLE patients was resistant to CBZ in 82% of patients,
      partially suppressed in 11% and completely suppressed in 7%. The effects of CBZ
      in tissue of MTLE patients did not depend on the type of activity, hippocampal
      pathology, excitability of the tissue, or equilibration time of the drug.
      Considering that CBZ has direct access to all compartments of the slice, our
      results suggest that CBZ-resistance mechanisms are located within the parenchyma
      of the dentate gyrus and contribute to drug resistance in the majority of MTLE
      patients. BBB-located drug-resistance mechanisms per se may play a minor role in
      this region, because CBZ-sensitivity was only observed in 7% of CBZ-resistant
      patients.

PMID- 16951411
TI  - Directed evolution by accumulating tailored mutations: thermostabilization of
      lactate oxidase with less trade-off with catalytic activity.
AB  - We assumed that adverse effects posed by introducing multiple mutations could be
      decomposed into those of each of the component mutations and that the risk could
      be reduced by the accumulation of mutations that were finely tuned for directed
      improvement of a specific property. We propose here a directed evolution strategy
      for improving a specific property with less effect on other ones. This strategy
      is composed of fine-tuning of mutations and their accumulation by our original
      mutation-assembling method. In this study, we selected lactate oxidase (LOX) as a
      model enzyme, because its directed evolution had showed a trade-off between
      thermostability and catalytic activity. Mutation profiling at each of the sites
      found by error-prone PCR revealed a strong inverse relationship between the two
      properties. Thermostable mutations with less effect on catalytic activity were
      selected at each site and accumulated with ideal combinations by our method. The
      resultant multiple mutants exhibited 5- to 10-fold superior catalytic activity
      and comparable thermostability with those created by accumulating thermostable
      mutations, which were not tuned for catalytic activity. This result demonstrates
      that the accumulation of fine-tuned mutations is an advantageous approach to
      reduce the risk of adverse effects posed by accumulating multiple mutations.

PMID- 16951412
TI  - Antibiotic susceptibility of 50 clinical isolates of Burkholderia pseudomallei
      from Singapore.

PMID- 16951413
TI  - Interferon-induced depression in chronic hepatitis C.
AB  - Since the success rate of the antiviral treatment of chronic hepatitis C (HCV) is
      increasing, the knowledge of side effects due to this therapy must also improve.
      Among these side effects, depression and other neuro-psychiatric symptoms are
      among the most important. It must be outlined that conditions may exist before
      treatment in relation to the viral infection. However, pegylated interferon (IFN)
      administration is associated with a huge increase in the importance and the
      incidence of neuro-psychiatric symptoms. This has led several experts to claim
      that antiviral therapy should not be given to HCV patients having psychiatric
      contraindications. This last assertion seems to be disproved on the basis of
      results of recent clinical trials using selective serotonin reuptake inhibitors
      (SSRI). Pathogenesis of these neuro-psychiatric symptoms, however, remains
      unknown although the impact of IFN on glucocorticoid receptors and on serotonin
      1A receptors is privileged. In conclusion, advances in HCV antiviral therapy and
      the comprehension and subsequent treatment of side effects induced by this
      therapy should allow us to treat more patients with greater success.

PMID- 16951415
TI  - Epigenetic regulators and histone modification.
AB  - Epigenetic inheritance is a key element in the adaptation of organisms to a
      rapidly changing environment without stably changing their DNA sequence. The
      necessary changes in its gene expression profiles are frequently associated with
      variations in chromatin structure. The conformation of chromatin is profoundly
      influenced by the post-translational modification of the histone proteins, the
      incorporation of histone variants, the activity of nucleosome remodelling factors
      and the association of non-histone chromatin proteins. Although the hierarchy of
      these factors is still not fully understood, genetic experiments suggest that
      histone-modifying enzymes play a major causal role in setting up a particular
      chromatin structure. In this article, the recent progress that was made to
      understand the molecular mechanisms of the targeting and regulation of histone
      modifiers and its implication for epigenetic inheritance are reviewed.

PMID- 16951416
TI  - HCOP: a searchable database of human orthology predictions.
AB  - The HUGO Gene Nomenclature Committee (HGNC) Comparison of Orthology Predictions
      (HCOP) search tool combines the human, mouse, rat and chicken orthology
      assertions made by PhIGs, HomoloGene, Ensembl, Inparanoid, Mouse Genome
      Informatics (MGI) and HGNC, enabling users to identify predicted ortholog pairs
      for a specified gene or genes. The HCOP resource provides a useful method to
      integrate, compare and access a variety of disparate sources of human orthology
      data. The HCOP search tool, data and documentation are available at
      http://www.gene.ucl.ac.uk/hcop.

PMID- 16951417
TI  - Detecting changes in financial protection: creating evidence for policy in
      Estonia.
AB  - Ninety-four per cent of the Estonian population is covered by public health
      insurance, but private expenditure has been increasing quickly both in real terms
      and as a percentage of total health expenditure. To date, little attention has
      been given to the impact this could have on the population's financial
      protection. Out-of-pocket payments, which account for the bulk of the private
      expenditure in many low- and middle-income countries, can push people into
      poverty and more generally represent too high a burden for some households. It is
      therefore very important that governments monitor the impact of out-of-pocket
      payments on health. Using an example from Estonia, this paper aims to illustrate
      that, if household budget survey data are available, monitoring a population's
      financial protection is not a complex undertaking. Further, by combining simple
      statistical analyses of these data with a good knowledge of a country's health
      system, it is possible to give a fairly detailed diagnostic of the nature of the
      population's coverage limitation. This allows for the presentation of easily
      interpretable results that can raise awareness among policy-makers and help to
      target adequate policy responses. Using Estonian household budget surveys from
      1995, 2001 and 2002, we show that the proportion of households who spend more
      than 20% of their capacity to pay on health increased from 3.4% in 1995 to 7.4%
      in 2002 and that in 2002, 1.3% of the population fell into poverty because of
      health payments. Logistic regression helps in identifying the population most at
      risk: elderly patients who belong to poor households and spend high amounts on
      medicines. This study, which can be replicated, did raise awareness among policy
      makers about the changes in financial protection over the years in Estonia.

PMID- 16951418
TI  - Acute splenic sequestration in female children with sickle cell disease in the
      North of Jordan.
AB  - The objective of this study was to evaluate the rate of acute splenic
      sequestration (ASSC) in patients with sickle beta-thalassaemia and sickle cell
      anaemia, the risk of recurrence in those who survive the first episode, and the
      relationship between ASSC episodes and subsequent hypersplenism. All patients
      with confirmed diagnosis of sickle cell disease at a tertiary referral teaching
      hospital, between January 1994 and December 2002 were interviewed and had their
      medical records reviewed. Seventy-seven patients with sickle cell disease were
      identified. Their ages ranged between 2 and 18 years (mean, 10.1 years). There
      were 35 females and 38 males. Thirty-seven (50.6%) had sickle beta-thalassaemia,
      and 36 (49.4%) had homozygous sickle cell anaemia. Of these, 26 had high level of
      Hb F and 11 had normal level of fetal haemoglobin (Hb F). Twenty-one patients
      (28%) had 63 episodes of acute splenic sequestration. Thirty-seven episodes were
      experienced by 12 patients with sickle beta-thalassaemia; of these 11 were major
      attacks with one fatality. Twenty-six episodes were experienced by nine patients
      with sickle cell anaemia. Splenomegaly and hypersplenism were greater in the
      acute splenic sequestration group than in the rest of the sickle cell anaemia
      patients, and the differences were extremely significant. ASSC was found in nine
      siblings of sickle beta-thalassaemia group, while none were found in the sickle
      cell anaemia group. The mean age of the first episode was significantly higher in
      sickle beta-thalassaemia, with significant differences in the levels of Hb F, Hb
      S, size of spleen and severity of crisis between both groups. In the sickle cell
      anaemia group the only significant difference between patients with and these
      without acute splenic sequestration was the difference in the size of spleen. In
      this study, the rate of ASSC in the sickle beta-thalassaemia patients was 32%, in
      contrast to 25% in the sickle cell anaemia patients. The risk of recurrence was
      about 70% in those who survived their first episodes. There was a close
      relationship between ASSC and subsequent hypersplenism. Important predictable
      factors for ASSC in sickle beta-thalassaemia patients were the presence of
      splenomegaly of more than 5 cm below the costal margin, history of acute splenic
      sequestration in siblings and high Hb F. Most of first episodes in sickle cell
      anaemia occur under the age of 2 years, while in sickle beta-thalassaemia the
      majority of patients have their first crisis at the age of > or =3.5 years.

PMID- 16951419
TI  - Neutrophil gelatinase-associated lipocalin (NGAL) correlations with cystatin C,
      serum creatinine and eGFR in patients with normal serum creatinine undergoing
      coronary angiography.

PMID- 16951420
TI  - Impact of enalapril on renal function in patients with severe chronic kidney
      disease.

PMID- 16951421
TI  - Dynamics at the slit diaphragm--is nephrin actin'?

PMID- 16951422
TI  - Steroid pulse therapy impaired endothelial function while increasing plasma high
      molecule adiponectin concentration in patients with IgA nephropathy.
AB  - BACKGROUND: Decreased plasma adiponectin is associated with impaired endothelial
      function and, thereby, increased risk for cardiovascular events. Glucocorticoid
      (GC) affects vascular endothelial cells either favourably or harmfully depending
      upon the dosages and duration. We examined the effect of GC pulse therapy on
      vascular endothelial function. METHODS: Fourteen young patients with IgA
      nephropathy were evaluated for flow-mediated vasodilation (FMD), plasma levels of
      adiponectin both in high molecular weight (HMW adiponectin) form and in single
      molecular form (total adiponectin), hepatocyte growth factor (HGF), asymmetric
      dimethylarginine (ADMA), and high-sensitive C-reactive protein, before and after
      a course of GC pulse therapy. RESULTS: GC pulse therapy significantly decreased
      FMD (from 7.2 +/- 2.6 to 5.7 +/- 2.5%, P < 0.01). Meanwhile, plasma adiponectin
      levels were significantly augmented (total adiponectin: from 10.2 +/- 4.0 to 12.1
      +/- 6.3 microg/ml, P < 0.05; HMW: from 6.5 +/- 3.2 to 7.7 +/- 3.3 microg/ml, P <
      0.05). In parallel, elevated concentrations of serum HGF (from 0.28 +/- 0.12 to
      0.63 +/- 0.38 ng/ml, P < 0.01) and plasma ADMA (from 0.45 +/- 0.07 to 0.53 +/-
      0.04 nmol/ml, P < 0.05) were observed. CONCLUSIONS: GC pulse therapy impaired
      endothelial function while increasing plasma adiponectin levels, which may in
      turn restore the endothelial function in patients with IgA nephropathy.

PMID- 16951423
TI  - Compliments from complement: A fourth pathway of complement activation?

PMID- 16951424
TI  - Duodenal diverticulosis in autosomal dominant polycystic kidney disease.

PMID- 16951425
TI  - A multi-dimensional model of clinical utility.
AB  - Clinical utility is an increasingly used concept in health care, but one that
      lacks an agreed formal definition or conceptualization. In this article, I show
      that the term is commonly used as a synonym for studies of clinical effectiveness
      and/or economic evaluations and argue that further factors relating to everyday
      working practice should be included under its auspices. I go on to develop a
      multi-dimensional model that outlines four factors in practitioners' judgements
      about clinical utility: appropriateness, accessibility, practicability, and
      acceptability.

PMID- 16951427
TI  - Which model of successful ageing should be used? Baseline findings from a British
      longitudinal survey of ageing.
AB  - BACKGROUND: there is increasing interest in how to age 'successfully' and in
      reaching consensus over its definition. OBJECTIVE: to assess different models of
      successful ageing, using a British longitudinal survey of ageing in 2000-1.
      SETTING: community settings in Britain. METHODS: five models of successful ageing
      were tested on a British cross-sectional population survey of 999 people aged
      65+. The models were biomedical, broader biomedical, social, psychological and
      lay based. RESULTS: the lay model emerged as the strongest. Respondents who were
      classified as successfully aged with this model, compared with those not
      successfully aged, had over five times the odds of rating their quality of life
      (QoL) as good rather than not good [odds ratio (OR) = 5.493, 95% confidence
      interval (95% CI) = 2.655-11.364]. CONCLUSION: the lay-based, more
      multidimensional, model of successful ageing predicted perceived QoL more
      powerfully than unidimensional models and should be used to evaluate the outcomes
      of health promotion in older populations.

PMID- 16951426
TI  - Nitration of p38 MAPK in the placenta: association of nitration with reduced
      catalytic activity of p38 MAPK in pre-eclampsia.
AB  - Peroxynitrite, a potent pro-oxidant formed from the interaction of superoxide and
      nitric oxide, has been widely reported to be nitrating tyrosine residues in
      proteins resulting in the formation of nitrotyrosine. Biological nitration of
      tyrosine, a footprint of oxidative injury, has been found to occur in various
      pathological states including pre-eclampsia, a leading cause of maternal
      mortality and increased perinatal mortality. Oxidative stress is a major
      contributor to endothelial dysfunction in pre-eclampsia. Previously, we have
      demonstrated increased nitrotyrosine immunostaining in placental villous vascular
      endothelium, surrounding vascular smooth muscle and villous stroma from pre
      eclamptic or diabetic pregnancies. Immunoprecipitation (IP) with
      antinitrotyrosine antibodies followed by immunoblot analysis identified increased
      nitration of phospho-p38 mitogen-activated protein kinase (MAPK) in the pre
      eclamptic placenta. The catalytic activity of p38 MAPK and concentration of
      phospho-p38 MAPK was also found to be reduced in placentae from pre-eclamptic
      pregnancies. Comparison of peptide masses of a 42-kDa protein obtained by mass
      spectrometry with masses of a theoretical tryptic digest of p38 MAPK that was
      modified by phosphorylation and nitration identified the protein to be p38 MAPK.

PMID- 16951428
TI  - An ethical analysis of alternative methods to obtain pluripotent stem cells
      without destroying embryos.
AB  - Although few ethical concerns exist regarding the use of adult stem cells, the
      field of embryonic stem cell research is fraught with moral qualms. Several
      alternative sources of pluripotent stem cells have recently been presented that
      try to sidestep the destruction of human embryos. The goal of these new proposals
      is to avoid embryo destruction, the main objection to embryonic stem cell
      research and thus introduce a type of stem cell research that would gain
      widespread approval and support. This article suggests that most embryo-saving
      alternatives fail to reach this goal given the concessions they require with
      regard to the speed of progress, technical complexity, safety and security of
      applications, degree of dependence on limited resources and extent of the field
      of application. The second part of the article identifies and analyses the two
      main strategies that alternative sources of pluripotent stem cells are based on
      and points out their shortcomings.

PMID- 16951429
TI  - Decreased ovarian reserve relates to pre-eclampsia in IVF/ICSI pregnancies.
AB  - BACKGROUND: Pre-eclampsia affects 2-10% of all pregnancies and is a major cause
      of maternal and fetal morbidity and mortality. As compared with the general
      population, IVF pregnancies are associated with a 2.7-fold risk of pre-eclampsia.
      An advanced age and associated subfertility in the IVF group reflects a general
      decrease in ovarian reserve, which itself has been linked to cardiovascular
      disease. We tested the hypothesis that decreased ovarian reserve is associated
      with pre-eclampsia as a vascular complication in IVF/ICSI pregnancies. METHODS:
      In this retrospective case-control study, 41 cases with a history of pre
      eclampsia were compared to 82 matched controls without hypertension or
      (pre)eclampsia. All pregnancies were established after IVF or ICSI. Several
      indicators of ovarian reserve such as variables related to basal ovarian function
      and response to hyperstimulation were compared in both the groups by multivariate
      analysis. The condition of the neonates was evaluated as well. RESULTS: A higher
      amount of total administered FSH and FSH per day, together with a lower number of
      obtained oocytes during IVF treatment, were associated with an increased risk to
      pre-eclampsia in a subsequent pregnancy. The administered FSH per follicle and
      per obtained oocyte showed even stronger relationships, the latter having the
      best predictive value. Neonatal outcome was comparable between the groups.
      CONCLUSION: Diminished responsiveness of the ovaries to FSH stimulation in an IVF
      cycle, reflecting decreased ovarian reserve, is associated with an increased risk
      of developing pre-eclampsia in a subsequent pregnancy.

PMID- 16951431
TI  - Pediatric intensive care in India: time for introspection and intensification.

PMID- 16951430
TI  - Structural basis for the mechanistic understanding of human CD38-controlled
      multiple catalysis.
AB  - The enzymatic cleavage of the nicotinamide-glycosidic bond on nicotinamide
      adenine dinucleotide (NAD(+)) has been proposed to go through an oxocarbenium ion
      like transition state. Because of the instability of the ionic intermediate,
      there has been no structural report on such a transient reactive species. Human
      CD38 is an ectoenzyme that can use NAD(+) to synthesize two calcium-mobilizing
      molecules. By using NAD(+) and a surrogate substrate, NGD(+), we captured and
      determined crystal structures of the enzyme complexed with an intermediate, a
      substrate, and a product along the reaction pathway. Our results showed that the
      intermediate is stabilized by polar interactions with the catalytic residue
      Glu(226) rather than by a covalent linkage. The polar interactions between
      Glu(226) and the substrate 2',3'-OH groups are essential for initiating
      catalysis. Ser(193) was demonstrated to have a regulative role during catalysis
      and is likely to be involved in intermediate stabilization. In addition, a
      product inhibition effect by ADP-ribose (through the reorientation of the
      product) or GDP-ribose (through the formation of a covalently linked GDP-ribose
      dimer) was observed. These structural data provide insights into the
      understanding of multiple catalysis and clues for drug design.

PMID- 16951432
TI  - Evaluating the suitability of prediction equations for lung function in Indian
      children: a practical approach.
AB  - OBJECTIVE: Although several prediction equations to evaluate peak expiratory flow
      rate (PEFR) of Indian children are available in literature, clinicians and
      researchers need to make a logical choice of which equation to use as reference.
      The aim was to demonstrate a practical approach to making such a logical choice
      by using prediction equations on our study population. METHODS: Eighteen linear
      regression equations generated on Indian children were chosen from available
      literature. PEFR measured on a Wright peak flow meter on 81 boys and 60 girls,
      aged between 8 and 13 years, was compared with the predicted values obtained from
      the equations. Data was systematically analyzed for the extent of over-estimation
      and under-estimation, correlation between the predicted and measured values and
      bias and limits of agreement using Bland-Altman plots. RESULTS: The correlation
      between observed and predicted values using the eighteen equations ranged between
      0.616 and 0.797 (for all P < 0.001). The Bland-Altman plots indicated that for
      all but three equations in boys and three equations in girls, lower measured
      values of PEFR were associated with higher predicted values. A final choice of a
      reference prediction equation was based on a combination of factors which
      included a high correlation between actual and predicted PEFR values, the bias of
      the estimate, the limits of agreement and the extent to which equations over or
      under-estimated PEFR. CONCLUSION: A practical approach to evaluate the
      applicability of prediction equations on an independent data set has been
      demonstrated.

PMID- 16951433
TI  - Cerebral edema in diabetic ketoacidosis.
AB  - Cerebral edema is the most important complication of diabetic ketoacidosis in
      children. It has a high mortality rate of 20 to 90% in different series. Twenty
      to 40% of survivors suffer from neurologic sequelae. The pathogenetic mechanisms
      are still controversial and the risk factors which are thought to predict its
      occurrence do not consistently correlate with cerebral edema in various studies.
      Prevention and recognition of early warning signs, such as decreased arousal,
      lethargy after initial improvement, headache, vomiting, relative bradycardia and
      relative hypertension, are crucial. Therapeutic guidelines to prevent cerebral
      edema in diabetic ketoacidosis include slow rehydration over about 48 hours,
      avoidance of hypotonicity and of unnecessary alkali therapy. Early recognition of
      cerebral edema and prompt institution of hypertonic therapy with mannitol may
      prevent permanent neurological sequelae.

PMID- 16951434
TI  - Pediatric practice.

PMID- 16951435
TI  - Predictors of outcome in children with hydrocarbon poisoning receiving intensive
      care.
AB  - The retrospective study included 48 children between 8.5 months--10 years,
      admitted to the PICU of an urban, tertiary care, teaching hospital in northern
      India from January 1995 to December 2001. Eighteen (38%) patients were hypoxemic
      on arrival, of which 8 (45%) required mechanical ventilation. Compared to the non
      hypoxemic children, the hypoxemic patients were more likely to have received
      gastric lavage before arrival to our center (Odds Ratio 23.2, 95% CI 2.4 - 560.7)
      and had higher frequency of severe respiratory distress and leucocytosis (Odds
      Ratio 8.0, 95% CI 1.79 -38.6). On multiple regression analysis, we could not
      identify any particular variable that could predict hypoxemia. Secondary
      pneumonia developed in 16 (33.3%), with the duration of PICU stay being longer in
      these patients as against those who did not (144 hours vs 72 hours, p <0.05). Two
      (4.2%) children died and one suffered hypoxic sequelae. Prior lavage, hypoxemia
      at admission, need for ventilation, secondary sepsis and ventilator related
      complications were associated with poor outcome.

PMID- 16951436
TI  - Impalpable testes--is imaging really helpful?
AB  - The study evaluated the role of imaging studies in the diagnosis of impalpable
      undescended testes. A total of 40 children referred with 45 impalpable
      undescended testes had an ultrasound scan and clinical examination by a pediatric
      surgeon. 22 out of these 45 testes were found to be palpable on clinical
      examination by a pediatric surgeon. Of the remaining 23 boys (23 units of
      testes), 21 underwent MRI scan for identification of testes and results were
      compared with findings at laparoscopy. The diagnostic agreement of ultrasound and
      MRI in correctly localizing the testes was 19% and 52% respectively whereas the
      sensitivity of detection was 60% and 55% respectively. Imaging studies therefore
      have a limited role in pre-surgical evaluation of boys with impalpable testes.

PMID- 16951437
TI  - Feeding of infants and young children in tsunami affected villages in
      Pondicherry.
AB  - The study was conducted to identify the problems related to feeding of children
      post tsunami in four villages in Pondicherry. Data were collected from 100
      randomly chosen families who had an infant or a young child below 3 years of age
      during Tsunami. Informants were the mothers. In the population studied, 30%
      mothers did not exclusively breast feed for 6 months; 58% bottle fed their
      children and 51% fed their infants with commercial formula. The occurrence of
      diarrhea was three times higher among children who were fed with free breast milk
      substitutes (BMS) than in those who were not fed with the same. Those
      populations, wherein a pre-existing tradition of artificial feeding is present,
      infants are at further risk during a crisis situation like Tsunami. Breast
      feeding practices need strengthening even in routine conditions to tackle a
      disaster rather than intervention after the disaster.

PMID- 16951438
TI  - Difficulties in the diagnosis of Kawasaki disease.
AB  - This study aims to highlight the difficulties faced in the clinical diagnosis of
      Kawasaki Disease (KD) presenting beyond the first week. This is a retrospective
      study of 25 cases of which only 36% met the criteria for classical and 8% was
      incomplete KD. Majority (56%) did not meet the criteria for classical KD; at the
      same time they were not incomplete / atypical cases. Difficulties arise in
      diagnosis of the cases presenting in the second week, as by that time many of the
      classical findings disappear or probably have not been present at all. In this
      scenario high index of suspicion for KD in a child presenting with fever, looking
      not that sick (Non toxic look) with bulbar conjunctivitis and oral mucositis
      helped us to reach the diagnosis. We incidentally observed Hyperemia of the Upper
      Eyelids in 32% of our cases, which might assist in the diagnosis.

PMID- 16951439
TI  - S252W mutation in Indian patients of Apert syndrome.
AB  - Two common mutations in the exon IIIa of fibroblast growth factor receptor 2
      account for majority of the cases of Apert syndrome. They can be analyzed by
      amplifying the segment followed by testing for the abolition of restriction
      sites. We evaluated two children with typical features of Apert syndrome. A
      segment of FGFR2 exon IIIa was amplified by polymerase chain reaction.
      Restriction fragment length polymorphism was analyzed using enzymes MboI and BglI
      respectively for S252W and P253R mutations. The DNA segment was sequenced using
      ABI 310 automated DNA fragment analyzer. Both the patients showed S252W
      mutations. DNA sequencing confirmed the results of the restriction fragment
      length polymorphism. Our study is the first report from Indian subcontinent to
      show the prevalence of S252W mutation among Apert syndrome patients from Indian
      origin.

PMID- 16951440
TI  - Neonatal Bartter syndrome.
AB  - Bartter syndrome is an inherited renal tubular disorder with hypokalemia,
      hypochloremic metabolic alkalosis, normal blood pressure with hyper-reninemia and
      increased urinary loss of sodium, potassium and chloride. We report an infant
      with neonatal Bartter syndrome, who improved with potassium supplements.

PMID- 16951441
TI  - Congenital erythropoeitic porphyria.

PMID- 16951442
TI  - Dual ectopic thyroid.

PMID- 16951443
TI  - Onset of obesity is late in affluent Bengali boys.

PMID- 16951444
TI  - Irrational combination of montelukast and bambuterol for management of childhood
      asthma.

PMID- 16951445
TI  - Ring chromosome 14 with epilepsy and development delay.

PMID- 16951446
TI  - Swyer-James Macleod syndrome.

PMID- 16951447
TI  - Parathyroid adenoma.

PMID- 16951448
TI  - Use of thermospot by slum dwelling mothers.

PMID- 16951449
TI  - Comments on 'Analysis of intracranial pressure during and after the infusion test
      in patients with communicating hydrocephalus'.
AB  - We comment on the paper by Juniewicz et al (2005 Physiol. Meas. 26 1039-48) which
      addresses problems in application of the Marmarou model for analyzing
      intracranial pressure changes during and after the infusion test, as well as the
      clinical relevance of the additional parameters obtained during prolonged
      infusion.

PMID- 16951451
TI  - Measurement of the specific heat capacity of liver phantom.
AB  - Phantoms are often used to simulate tissue during the development, testing and
      calibration of medical devices. In order to infer the specific absorption rate
      (SAR) and resistive heating in phantoms from temperature measurements, the
      specific heat capacity and density of the phantom are needed. Stauffer et al
      (2003 Int. J. Hyperth. 19 89-101) developed several phantoms that mimic
      dielectric properties of liver tissue at 915 MHz. However, thermal properties of
      the phantoms were not presented. We have measured specific heat capacities and
      densities for these phantoms. We also present dielectric properties for these
      phantoms measured from 0.7 to 20 GHz, including 2.45 GHz--a commonly used
      frequency for microwave hyperthermia and ablation.

PMID- 16951452
TI  - Simultaneous assessment of posture and limb movements (e.g., periodic leg
      movements) with calibrated multiple accelerometry.
AB  - This study describes new applications for the method of calibrated multiple
      accelerometry, which detects posture and distinct motion patterns, and limb
      movements continuously. The aim of our study was to evaluate this assessment
      technique in terms of its suitability for exploring the relationships between
      pathological limb movement activity (e.g., periodic leg movements) and posture.
      The new method proved to be appropriate for the simultaneous assessment of
      pathological leg jerks and posture and provided a means to revealing possible
      relations. Generally, our study demonstrates the application of this (ambulatory)
      assessment technique in the field of sleep and neurological disorders.

PMID- 16951453
TI  - Improved perfusion system for bipolar radiofrequency ablation of liver:
      preliminary findings from a computer modeling study.
AB  - Current systems for radiofrequency ablation of liver tumors are unable to
      consistently treat tumors larger than 3 cm in diameter with a single electrode in
      a single application. One of the strategies for enlarging coagulation zone
      dimensions is to infuse saline solutions into the tissue through the active
      electrodes. Nevertheless, the uncontrolled and undirected diffusion of boiling
      saline into the tissue has been associated with irregular coagulation zones and
      severe complications, mainly due to reflux of saline along the electrode path. In
      order to improve the perfusion bipolar ablation method, we hypothesized that the
      creation of small monopolar coagulation zones adjacent to the bipolar electrodes
      and previous to the saline infusion would create preferential paths for the
      saline to concentrate on the targeted coagulation zone. Firstly, we conducted ex
      vivo experiments in order to characterize the monopolar coagulation zones. We
      observed that they are practically impermeable to the infused saline. On the
      basis of this finding, we built theoretical models and conducted computer
      simulations to assess the feasibility of our hypothesis. Temperature
      distributions during bipolar ablations with and without previous monopolar
      coagulation zones were obtained. The results showed that in the case of monopolar
      coagulation zones the temperature of the tissue took longer to reach 100 degrees
      C. Since this temperature value is related to rise of impedance, and the time
      necessary for this process is directly related to the volume of the coagulation
      zone, our results suggest that monopolar sealing would allow larger coagulation
      zones to be created. Future experimental studies should confirm this benefit.

PMID- 16951454
TI  - Classification of a known sequence of motions and postures from accelerometry
      data using adapted Gaussian mixture models.
AB  - Accelerometry shows promise in providing an inexpensive but effective means of
      long-term ambulatory monitoring of elderly patients. The accurate classification
      of everyday movements should allow such a monitoring system to exhibit greater
      'intelligence', improving its ability to detect and predict falls by forming a
      more specific picture of the activities of a person and thereby allowing more
      accurate tracking of the health parameters associated with those activities. With
      this in mind, this study aims to develop more robust and effective methods for
      the classification of postures and motions from data obtained using a single,
      waist-mounted, triaxial accelerometer; in particular, aiming to improve the
      flexibility and generality of the monitoring system, making it better able to
      detect and identify short-duration movements and more adaptable to a specific
      person or device. Two movement classification methods were investigated: a rule
      based Heuristic system and a Gaussian mixture model (GMM)-based system. A novel
      time-domain feature extraction method is proposed for the GMM system to allow
      better detection of short-duration movements. A method for adapting the GMMs to
      compensate for the problem of limited user-specific training data is also
      proposed and investigated. Classification performance was considered in relation
      to data gathered in an unsupervised, directed routine conducted in a three-month
      field trial involving six elderly subjects. The GMM system was found to achieve a
      mean accuracy of 91.3%, distinguishing between three postures (sitting, standing
      and lying) and five movements (sit-to-stand, stand-to-sit, lie-to-stand, stand-to
      lie and walking), compared to 71.1% achieved by the Heuristic system. The
      adaptation method was found to offer a mean accuracy of 92.2%; a relative
      improvement of 20.2% over tests without subject-specific data and 4.5% over tests
      using only a limited amount of subject-specific data. While limited to a
      restricted subset of possible motions and postures, these results provide a
      significant step in the search for a more robust and accurate ambulatory
      classification system.

PMID- 16951455
TI  - Effects of age on muscle as measured by electrical impedance myography.
AB  - Electrical impedance myography (EIM) is a painless and non-invasive technique for
      the assessment of muscle which we apply here to the effects of normal aging. The
      paper presents a cross-sectional analysis of EIM data from the quadriceps and
      tibialis anterior of 100 healthy subjects (44 men, 56 women, ages 18-90 years).
      The principal EIM parameter, the spatially averaged phase theta(avg), shows a
      roughly quadratic reduction with increasing age, declining more steeply beyond 60
      years. The correlation was stronger in men (quadriceps: r2 = 0.68 for men, 0.52
      for women; tibialis anterior: r2 = 0.74 for men, 0.38 for women; p < 0.001
      throughout). Additionally, four subjects (age greater than 75 years) were asked
      to return for repeat testing several years after their initial assessment. These
      longitudinal results qualitatively confirm the cross-sectional data, though with
      greater reductions in theta(avg) at high age. The findings of this study support
      the potential use of EIM as a simple and effort-independent test of muscle health
      in the elderly.

PMID- 16951456
TI  - Thoracic versus whole body bioimpedance measurements: the relation to hydration
      status and hypertension in peritoneal dialysis patients.
AB  - The whole body bioimpedance technique is a highly promising non-invasive,
      reproducible, fast and inexpensive bed-side method for monitoring hydration
      status. Using segmental bioimpedance measurements, it is possible to obtain
      information about the fluid change in each body segment (Song, Lee, Kim and Kim
      1999 Perit. Dial. Int. 19 386-90). In this pilot study we have measured 25 male
      patients (30-65 yr, BMI 20-32 kg m(-2)) undergoing continuous ambulatory
      peritoneal dialysis (CAPD). Tetrapolar impedance measurements were obtained using
      the right-side technique (whole body), and a segmental impedance method focused
      in the thorax region. Blood pressure (BP) measurements were taken manually with a
      sphygmomanometer. Patients were classified as either stable (group 0) or unstable
      (group 1) using clinical parameters of overall cardiovascular risk. The
      Mahalanobis distance (dM2) was calculated for the mean blood pressure (BP(mean)),
      and the impedance parameter R normalized by body height H for the right-side
      (R(RS)/H) and the thorax segment (R(TH)/H). Differences between groups were
      significant (p < 0.0001) for R(TH)/H and for BP(mean), and less significant (p =
      0.016) for R(RS)/H. Group 1 patients showed a small dM2 as compared with a
      reference patient (a critical patient with acute lung edema) with high BP(mean)
      and low values of R(TH)/H and R(RS)/H. Moreover, Group 0 patients showed a larger
      dM2 with respect to the reference patient, with lower BP(mean) and higher values
      of R(TH)/H and R(RS)/H. All patients classified as unstable by clinical
      assessment were correctly classified using R(TH)/H in conjunction with BP(mean)
      using dM2. Segmental-monofrequency non-invasive bioimpedance of the thoracic
      region could provide a simple, objective non-invasive method of support for
      facilitating the clinical assessment of CAPD patients.

PMID- 16951457
TI  - Model based and experimental investigation of respiratory effect on the HRV power
      spectrum.
AB  - The role of respiration in the genesis of heart rate variability (HRV) has been
      the subject matter of many experimental and modeling studies. It is widely
      accepted that the high frequency (HF) peak of a HRV power spectrum, which is
      centered at the average respiratory frequency, is caused by mechanisms activated
      by respiration. On the other hand, there is a debate on the possible role of
      respiration in the genesis of the low frequency (LF) peak which is usually
      centered around 0.1 Hz. In this study, a comprehensive cardiorespiratory
      interaction model is used to test various hypotheses regarding the role of
      respiration in the LF peak of HRV. In this model, chest and abdomen circumference
      signals and lung volume signal are used as respiratory inputs. Simulations are
      made for periodic, spontaneous and slightly irregular respiratory patterns, and
      it is observed that the more low frequency (LF) power there in the respiratory
      signals, the more LF power there in the model-predicted HRV. Experiments on nine
      volunteers are also performed for the same respiratory patterns and similar
      results are observed. Furthermore, the actual measured respiratory signals are
      input to the model and the model predicted and the actual HRVs are compared both
      in time domain and also with respect to their power spectra. It is concluded in
      general that respiration not only is the major contributor to the genesis of the
      HF peak in the HRV power spectrum, but also plays an important role in the
      genesis of its LF peak. Thus, the LF/HF ratio, which is used to assess
      sympathovagal balance, cannot be correctly utilized in the absence of
      simultaneous monitoring of respiration during an HRV test.

PMID- 16951458
TI  - Dependence of heart rate variability on heart period in disease and aging.
AB  - The aim of this study was to compare the dependence of heart rate variability
      (HRV) on heart period (RR interval length) under different physiological and
      pathological states in order to detect changes in HR modulation. The dependence
      of HRV on the RR interval length in healthy elderly subjects, congestive heart
      failure (CHF) patients and one patient with a transplanted heart (T) was compared
      with healthy young subjects. Spectral powers, sample entropy (SampEn) and short
      term fractal scaling exponent (alpha1) were determined from 24 h free-running
      recordings. For the same HR, HRV measures were different in different groups. In
      healthy subjects HRV measures depended on RR interval length and all spectral
      powers were highly correlated, although reduced in elderly subjects. SampEn at
      high HR was the most sensitive quantity to changes induced by aging. In disease,
      CHF and T, an achievable HR range was decreased, all spectral powers were
      reduced, but correlated, and the dependence of HRV measures on RR was lost. There
      was an evident difference in the dependence of nonlinear on linear measures
      between young subjects and all the other studied groups. In disease the reduction
      in autonomic control was associated with the decrease in short-range correlation
      and regularity in RR series. We have concluded that the analysis of HRV measures
      as functions of RR interval length can reveal important aspects of HR control
      that might be lost in averaging.

PMID- 16951459
TI  - Does centripetal acceleration affect trunk flexion monitoring by means of
      accelerometers?
AB  - Micro electro-mechanical and NANO technologies are sensibly reducing circuit and
      geometrical errors in accelerometer sensors. These sensors are often used as
      portable inclinometer sensors for trunk flexion monitoring in clinical
      applications. In this case, the rotating trunk generates centripetal
      acceleration, an error source that technological efforts cannot eliminate. This
      study analysed the effect of this source for typical human monitoring conditions
      by simulations and clinical validation using a wearable device with rate
      gyroscopes and accelerometers (Giansanti and Maccioni 2005 Physiol. Meas. 26 689
      705). Results showed that this error source did not affect long-term monitoring
      applications (Mathie et al 2004 Physiol. Meas. 25 R1-R20) but in the short-term
      monitoring caused a mean angular error equal to 0.96 degrees for the most
      critical single-task application represented by the sit-to-stand.

PMID- 16951460
TI  - Transthoracic impedance study with large self-adhesive electrodes in two
      conventional positions for defibrillation.
AB  - External defibrillation requires the application of high voltage electrical
      impulses via large external electrodes, placed on selected locations on the
      thorax surface. The position of the electrodes is one of the major determinants
      of the transthoracic impedance (TTI) which influences the intracardiac current
      flow during electric shock and defibrillation success. The variety of factors
      which influence TTI measurements raised our interest to investigate the range of
      TTI values and the temporal TTI variance during long-term application of
      defibrillation self-adhesive electrodes in two conventional positions on the
      patient's chest--position 1 (sub-clavicular/sub-axillar position) and position 2
      (antero-posterior position). The prospective study included 86 randomly selected
      volunteers (39 male and 49 female, 67 patients with normal skin, 13 patients with
      dry skin and 6 patients with greasy skin, 16 patients with chest pilosity and 70
      patients without chest pilosity). The TTI was measured according to the
      interelectrode voltage drop obtained by passage of a low-amplitude high-frequency
      current (32 kHz) between the two self-adhesive electrodes (active area about 92
      cm2). For each patient, the TTI values were measured within 10 s, 1 min and 5 min
      after sticking the electrodes to the skin surface, independently for the two
      tested electrode positions. We found that the expected TTI range is between 58
      Omega and 152 Omega for position 1 and between 55 Omega and 149 Omega for
      position 2. Although the two TTI ranges are comparable, we measured significantly
      higher TTI mean of about (107.2 +/- 22.3) Omega for position 1 compared to (96.6
      +/- 19.2) Omega for position 2 (p = 0.001). This fact suggested that the antero
      posterior position of the electrodes is favourable for defibrillation. Within the
      investigated time interval of 5 min, we observed a significant TTI reduction with
      about 6.9% (7.4 Omega/107.2 Omega) for position 1 and about 5.3% (5.1 Omega/96.6
      Omega) for position 2. We suppose that the long-term application of self-adhesive
      electrodes would lead to improvement of the physical conditions for conduction of
      the defibrillation current and to diminution of energy loss in the electrode-skin
      contact impedance. We found that gender is important when position 1 is used
      because women have significantly higher TTI (111 +/- 20.3) Omega compared to the
      TTI of men (102.6 +/- 24) Omega (p = 0.0442). Although we found some specifics of
      the electrode-skin contact layer, we can conclude that because of the
      insignificant differences in TTI, the operator of the defibrillator paddles does
      not need to take into consideration the skin type and pilosity of the patients.
      Analysis of the correlations between TTI and the individual patient
      characteristics (chest size, weight, height, age) showed that these patient
      characteristics are unreliable factors for prediction of the TTI values and
      optimal defibrillation pulse parameters and energy.

PMID- 16951461
TI  - Measurement of cardiac output by open-circuit acetylene uptake: a computer model
      to quantify error caused by ventilation-perfusion inequality.
AB  - The ability to assess cardiac output (Q(T)) noninvasively has been the focus of
      interest for many researchers. While the open-circuit acetylene (C2H2) method
      seems promising, it is prone to error due to ventilation-perfusion (V/Q)
      inequality. Measurements during exercise, at high altitude or in patients with
      chronic obstructive pulmonary disease (COPD) could be unreliable and further
      validation studies under these circumstances may be needed. We used a computer
      model based on formulae derived from the multiple inert gas elimination technique
      to quantify error in Q(T) measurements resulting from V/Q inequality at rest,
      during exercise or at high altitude. Moreover, potential errors encountered in
      patients with COPD were quantified. In healthy subjects, V/Q inequality related
      measurement error seems negligible, under both normoxic and hypoxic conditions
      and especially during exercise. In COPD, errors up to 20% at rest and up to 15%
      during exercise are expected. It is therefore concluded from our model that the
      open-circuit C2H2 uptake method is expected to be accurate in normal subjects.
      Its validity in COPD needs further study.

PMID- 16951462
TI  - Transmittance photoplethysmography with near-infrared laser diodes in intra
      peritoneal organs.
AB  - Photoplethysmography and pulse oximetry are techniques based on optical
      principles, which are widely used in medical practice for non-invasive
      monitoring. There are some processes which may affect specific organs or parts
      without a significant repercussion on the information provided non-invasively.
      Here, we report on the preliminary results obtained by transmittance
      photoplethysmography in pig intra-peritoneal organs along a surgical
      intervention, using a measurement system based on two near-infrared laser diodes.
      Analysis of the signals recorded at 750 nm and 850 nm in the mesentery root,
      mesocolon, gastric wall and aorta artery has shown the affordability of
      performing in situ photoplethysmography for visceral perfusion evaluation.

PMID- 16951463
TI  - Automatic detection, segmentation and assessment of snoring from ambient acoustic
      data.
AB  - Snoring is a prevalent condition with a variety of negative social effects and
      associated health problems. Treatments, both surgical and therapeutic, have been
      developed, but the objective non-invasive monitoring of their success remains
      problematic. We present a method which allows the automatic monitoring of snoring
      characteristics, such as intensity and frequency, from audio data captured via a
      freestanding microphone. This represents a simple and portable diagnostic
      alternative to polysomnography. Our system is based on methods that have proved
      effective in the field of speech recognition. Hidden Markov models (HMMs) were
      employed as basic elements with which to model different types of sound by means
      of spectrally based features. This allows periods of snoring to be identified,
      while rejecting silence, breathing and other sounds. Training and test data were
      gathered from six subjects, and annotated appropriately. The system was tested by
      requiring it to automatically classify snoring sounds in new audio recordings and
      then comparing the result with manually obtained annotations. We found that our
      system was able to correctly identify snores with 82-89% accuracy, despite the
      small size of the training set. We could further demonstrate how this
      segmentation can be used to measure the snoring intensity, snoring frequency and
      snoring index. We conclude that a system based on hidden Markov models and
      spectrally based features is effective in the automatic detection and monitoring
      of snoring from audio data.

PMID- 16951464
TI  - [Incidence of and prognosis for osteoporotic fracture].
AB  - As the population rapidly ages, osteoporosis has been a serious problem. The
      incidence of hip fracture, which is the most serious complication for
      osteoporosis, is increasing and over 1,000 thousands per year, while, the
      incidence of vertebral fracture is still five times more than that of hip
      fracture. The incidence of hip fracture, vertebral fracture and proximal humeral
      fracture increases with ages, however, that of distal radial fracture does not.
      Fracture, especially hip fracture and vertebral fracture, is associated with
      mortality. Thus, prevention for fracture in the elderly is very important issue.

PMID- 16951465
TI  - [Primary, secondary and tertiary prevention of osteoporosis].
AB  - Preventive procedures of a disease can be classified into three levels. Primary
      prevention protects healthy people against the disease, secondary prevention
      screens people at high risk for the disease or with the disease of an early stage
      and treats them, and tertiary prevention rehabilitates patients with the disease
      through medical treatment. Many preventive measures for osteoporosis have been
      shown to have strong or fair evidence for their validity in each of the three
      levels. It is necessary to provide people with different risks of osteoporosis
      valid preventive measures which correspond to their risk profiles. The primary
      prevention for osteoporosis should be provided all the people as comprehensive
      measures against other lifestyle-related diseases, the secondary prevention
      should target people at higher risk of osteoporotic fractures, and the tertiary
      prevention should be provided the patients and at frail elderly people using
      medical or long-term care insurance.

PMID- 16951466
TI  - [Frequency of falls and their prevention].
AB  - In Japan, one in five elderly persons has experienced falls in the past one year,
      and 10%of these falls lead to fractures. In the elderly, fracture is a major
      factor impeding the independence of daily activities and quality of life, and
      hence is an important problem. Given this situation, many studies that validate
      the effects of exercise programs aiming at the prevention of falls have been
      reported recently. Especially, the strategy of disseminating falls prevention
      exercise programs for the elderly in the community aiming to raise the falls
      prevention awareness and maintain or improve physical function is expected to
      lower the frequency of falls as well as to prolong functional independence and
      extend the healthy life-span.

PMID- 16951467
TI  - [Treatment and management of severe osteoporosis].
AB  - Because there is an extremely high probability of new fractures occurring in
      cases in which there are pre-existing fractures, it is easy for such patients to
      develop severe osteoporosis. We therefore must correctly ascertain any existence
      of either vertebral or hip fractures. High values of bone resorption markers
      reflect the existence of microfractures, so it is necessary to be careful due to
      the high risk of new fractures. Kinesitherapy for severe osteoporosis focuses on
      therapeutic exercise, walking, balance drills, and so forth with the aim of
      maintaining muscular strength and thus preventing falls. For severe osteoporosis
      such as senile osteoporosis and glucocorticoid-induced osteoporosis,
      bisphosphonates are currently the only medication that has been proven to be
      effective for preventing fractures. For the treatment of disuse osteoporosis
      stemming from paralysis, etc., the intravenous injection of bisphosphonates is
      able to suppress the decline in bone mass, but there is still very little
      evidence of its fracture prevention effect.

PMID- 16951468
TI  - [Diagnosis of osteoporosis from the viewpoint of bone quality].
AB  - It is generally known that approximately 70 percent of bone strength is explained
      by bone mineral density, and the remaining 30 percent by "bone quality".
      Especially, in the monitoring of treatment, bone mineral density cannot fully
      explain the efficacy upon the risk of fracture. "Bone quality" has two aspects:
      structure property and material property. They are both influenced by bone
      turnover and have a relation to bone strength. From the viewpoint of diagnosis of
      osteoporosis, the factors of bone quality that can be clinically evaluated, are
      bone biomarkers as indices of bone remodeling, and structure property including
      bone geometry and trabecular microstructure. This article discusses the
      evaluation of bone quality and its clinical significance.

PMID- 16951469
TI  - [Role of OPG in regulation of bone remodeling].
AB  - Osteoprotegerine (OPG) acts as a decoy receptor for receptor activator of NF
      kappaB (RANK) ligand (RANKL) to compete against RANK. OPG-deficient mice exhibit
      severe osteoporosis with accelerated bone remodeling. In human, several
      homozygous mutations in OPG gene were found in patients with juvenile Paget's
      disease. Missense mutations in cysteine residues in ligand binding domain, as
      well as complete deletion mutation, were associated with a severe phenotype
      characterized by enhanced bone remodeling and deformity. Serum RANKL level was
      elevated in OPG-deficient mice and a patient with complete deletion mutation.
      These results suggest that OPG represses the production of soluble form of RANKL.
      The elevated RANKL level in serum of OPG-deficient mice was not reduced by
      treatment with anti-resorbing agent, risedronate, but was upregulated by 1,25
      (OH) (2)D(3) administration or ovariectomy.

PMID- 16951470
TI  - [Molecular mechanism of tissue-specific actions of SERM].
AB  - Selective estrogen receptor modulator (SERM) is designated as synthetic ligands
      for estrogen receptors (ERs), exhibiting tissue-specific agonisitic/antagonisitic
      activities. Among SERM, raloxifen is a most clinically successful as an anti
      oseteoporotic agent. Such tissue-specific actions of SERM are presumed to mediate
      through unusual structure alteration of liganded ERs coupled with co-regulator
      recruitments.

PMID- 16951471
TI  - [Current topics in drug therapy aiming at bone resorption].
AB  - The majority of current therapeutics for osteoporosis is targeting bone
      resorption by osteoclasts. Bisphosphonates, potent and specific inhibitors of
      bone resorption, are widely used for postmenopausal osteoporosis on the basis of
      large scale clinical trials which proved their ability to reduce fracture risk.
      Estrogen, which had been widely used in the US, lost its position of standard
      drug therapy for osteoporosis because of the recent evidence of increasing
      adverse events. On the other hand, the market share of selective estrogen
      receptor modulators (SERMs), which utilize valuable functions of estrogen and
      have less adverse effects, has been climbing. Other novel therapeutic agents
      which aim at signal transduction of osteoclast differentiation and activation are
      promising as specific inhibitors of bone resorption.

PMID- 16951472
TI  - [Anabolic treatment for osteoporosis: PTH treatment].
AB  - There are several lines of evidence about the effectiveness of parathyroid
      hormone (PTH) as a bone anabolic reagent for the treatment of osteoporosis, and
      the large-scale randomized controlled trial revealed that PTH increases and
      reduces lumbar spine bone mineral density and fracture risk, respectively, more
      potently than other inhibitors for bone resorption. Moreover, alendronate was
      useful for the further increase in bone mineral density after the withdrawal of
      PTH treatment, and the combined treatment of PTH and raloxifene was additive. On
      the other hand, strontium ranelate significantly inhibited osteoporotic fractures
      in randomized placebo controlled trial, which is expected as a new bone anabolic
      reagent for osteoporosis.

PMID- 16951473
TI  - [Fracture risk assessment tool].
AB  - World Health Organization (WHO) has proposed the use of 10-year absolute risk for
      fracture (calculated based on incidence and life span) using clinical risk
      factors as new intervention thresholds. Eight risk factors to be included in the
      fracture assessment risk tool are age, bone mineral density or body mass index
      (BMI) when bone density is not available, steroid use, parental history of
      femoral neck fracture, history of osteoporotic fracture, smoking, excessive
      alcohol consumption, and rheumatoid arthritis. WHO has proposed that a treatment
      intervention threshold be established in accordance with the medical situation in
      each country.

PMID- 16951474
TI  - [Progress in external hip protectors].
AB  - Hip fractures are a major cause of disability, impairment and death in elderly
      people. It has been reported that bisphosphonates significantly reduce the risk
      of hip fracture among elderly women with confirmed osteoporosis but not among
      elderly women selected primarily on the basis of risk factors other than low bone
      mineral density. External hip protectors have been developed as a measure of
      reducing the impact of the fall and thereby the chance of hip fractures in such
      high risk people. The results of 14 randomized controlled trials for the
      prevention of hip fractures by using hip protectors have been reported until
      2004. However, Cochrane review of hip protectors has concluded that their
      effectiveness is uncertain. Although further research is required with different
      conditions, the most important issue of hip protectors is the low adherence rate.

PMID- 16951475
TI  - [Current research in adequate treatment by Osteoporosis Research Group].
AB  - In 2002, Adequate Treatment of Osteoporosis (A-TOP) Research Group was organized
      to obtain the evidence for treatment of osteoporosis in Japan. The group has
      designed and carried out an intervention trial plan, Japanese Osteoporosis
      Intervention Trial (JOINT)-02 to demonstrate the possible combination effect of
      alendronate plus active vitamin D(3). In this report, we summarize the past
      activity and the perspective of the future of the A-TOP research group.

PMID- 16951476
TI  - [Therapeutic effects of risedronate on Paget's disease of bone].
AB  - Paget's disease of bone (PDB) is a chronic disorder characterized by focal
      abnormalities of bone turnover. The characteristic feature of PDB is excessive
      osteoclastic bone resorption coupled to increased and disorganized bone
      formation. Although PDB is rare in Japan, it is quite common in most European
      countries, except for Scandinavia. The recommended regimens for bisphosphonates
      use in various parts of the world. Calcitonin and etidronate are approved by the
      Ministry of Health, Labour and Welfare in Japan to treat PDB. Risedronate is
      currently under development for use in the treatment of PDB in Japan.

PMID- 16951477
TI  - [Bisphosphonate therapy for osteoporosis and bone strength].
AB  - Bisphosphonates are now the most widely used drugs for osteoporosis. When
      bisphosphonate is given, the response varies directly with the rate of bone
      turnover at baseline. In high turnover osteoporosis there could be a gain in bone
      mass, but it reach a plateau after 2 to 3 years. In normal or low turnover
      osteoporosis bone mass is stabilized or slightly increased. The best indication
      of bisphosphonate use for osteoporosis is high turnover. In high turnover
      osteoporosis bisphosphonate therapy is effective in increasing the stiffness and
      the toughness (bone strength) by increasing the mean degree of mineralization of
      bone tissue through the prolongation of secondary mineralization. But the long
      term use of bisphosphonate would result in highly mineralized bone and disturbed
      repair of microcracks by inhibition of bone remodeling. Intermittent use of
      bisphosphonate could be recommended to avoid the deterioration of bone quality.

PMID- 16951478
TI  - [Selective estrogen receptor modulators (SERMs)].
AB  - Selective estrogen receptor modulators (SERMs) bind to estrogen receptor (ER) and
      develop tissue-selective actions as estrogen agonists or antagonists. As such,
      SERMs have been developed to exert estrogen-like beneficial effects against some
      disorders including osteoporosis, while reducing estrogen-related risks,
      including breast cancer. Prevention of vertebral fractures by a SERM, raloxifene
      (RLX), in osteoporotic postmenopausal women has been well established. RLX does
      not increase or decrease cardiovascular events, overall mortality, cardiovascular
      mortality or the overall number of strokes, but there appears to be a small
      increase in stroke mortality. Both RLX and tamoxifen similarly reduce the risk of
      ER-positive invasive breast cancer. At the same time, RLX treatment is associated
      with 36% fewer uterine cancer incidence and 29% less thromboembolic events.
      Keeping these results in mind, it is our responsibility to critically evaluate
      and decide timing and length of treatment, as well as subjects with benefits or
      risks for the treatment of osteoporosis by SERMs.

PMID- 16951479
TI  - [Protective effects of vitamin K against osteoporosis and its pleiotropic
      actions].
AB  - Vitamin K is a nutrient originally identified as an essential factor for blood
      coagulation. Recently, vitamin K has emerged as a potential protector against
      osteoporosis and hepatocarcinoma. Accumulated evidence indicates that subclinical
      non-hemostatic vitamin K deficiency in extrahepatic tissues, particularly in
      bone, exists widely in the otherwise healthy adult population. Both vitamin K(1)
      and K(2) have been shown to exert protective effects against osteoporosis.
      Moreover, therapeutic potential of vitamin K(2) as an anti-hepatoma drug has been
      recently highlighted. Most of the new biological functions of vitamin K in bone
      and hepatoma cells are considered to be attributable to promotion of gamma
      carboxylation of glutamic acid residues in vitamin K-dependent proteins, which is
      shared by both vitamins K(1) and K(2). In contrast, vitamin K(2)-specific, gamma
      carboxylation-unrelated functions have also been demonstrated. These functions
      include stimulation of steroid and xenobiotic receptor (SXR)-mediated
      transcription and anti-oxidant property. Thus, biological differences between
      vitamins K(1) and K(2), and a potential involvement of gamma-carboxylation
      independent actions in the new roles of vitamin K remain open issues. Molecular
      bases of coagulation-unrelated pleiotropic actions of vitamin K and its
      implications in human health deserve further investigations.

PMID- 16951480
TI  - [Treatment of osteoporosis from the socioeconomic perspectives].
AB  - Health economic evaluation for osteoporosis suffers from methodological
      limitations. For example, osteoporosis results in various types of fractures each
      with different impact on patients. Another example is that some therapeutic drugs
      have extraskeletal benefits and adverse events. Osteoporosis and resultant
      fracture has profound effects on patients' life expectancy and quality of life,
      which, however, is not well understood. To promote the health economic evaluation
      for osteoporosis is our urgent research project in Japan.

PMID- 16951481
TI  - [Destruction of articular cartilage].
AB  - Proinflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis
      factor alpha (TNF alpha), have been implicated in the dysregulation of bone and
      cartilage remodelling characteristic of rheumatoid arthritis (RA) and/or
      osteoarthritis (OA). These cytokines increase production of factors that
      stimulate cartilage matrix degradation such as metalloproteinases. The matrix
      metalloproteinases (MMPs), the a disintegrin and metalloproteinase (ADAMs) and a
      disintegrin and metalloproteinase with thrombospondin repeats (ADAM-TSs) are
      secreted by many cell types including chondrocytes and cells in the synovium
      under the influences of cytokines. The role of the matalloproteinases in the
      irreversible degradation of articular cartilage has been extensively documented.
      We have already succeeded in halting the progression of joint damage by RA using
      anti-TNF therapy. The precise understanding of the roles of metalloproteinases
      should provide new therapeutic strategies for OA.

PMID- 16951482
TI  - [Asporin, a susceptibility gene for osteoarthritis].
AB  - Osteoarthritis (OA) is the most common form of human arthritis. Genetic factors
      have been implicated in OA. Through a candidate gene-association study, we found
      association between asporin and OA. Asporin is an extracellular matrix component
      expressed abundantly in the articular cartilage of OA patients. A significant
      association between a polymorphism in the aspartic acid (D) repeat of the asporin
      gene (ASPN) and knee OA was found; the D14 allele of ASPN is over-represented
      relative to the common D13 allele, and its frequency increases with disease
      severity. The D14 allele is also over-represented in patients with hip OA. The
      association of asporin is replicated in European population by meta-analysis.
      Asporin suppresses transforming growth factor-beta (TGF-beta)-mediated expression
      of aggrecan and type II collagen genes and reduced proteoglycan accumulation in
      an in vitro model of chondrogenesis. Asporin co-localized to and bound to TGF
      beta, and inhibited TGF-beta-Smad signal. Clarification of molecular pathway of
      OA relating to asporin and TGF-beta would lead to order-made medicine and novel
      therapeutic strategies for OA.

PMID- 16951483
TI  - [Autoantigen and molecular chaperone in rheumatoid arthritis--their roles in
      metabolism of chondrocytes].
AB  - The endoplasmic reticulum chaperone; heat shock protein/rheumatoid arthritis
      related antigen (HSP47/RA-A47), in addition to its important intercellular
      functions for collagen maturation and secretion, has chondrocytes-destructive
      roles such as induction of endoplasmic reticulum (ER)-stress and metabolic gene
      expressions result in apoptosis when HSP47/RA-A47 is downregulated. Extracellular
      HSP47/RA-A47 may act as an autoantigen, but also regulate autoimmune
      inflammation. It is, therefore, a potential new biologic therapy for rheumatoid
      arthritis.

PMID- 16951484
TI  - ApoE polymorphism is associated with C-reactive protein in low-HDL family members
      and in normolipidemic subjects.
AB  - The study was aimed to compare inflammatory parameters between carriers of apoE4
      isoforms (apoE4/3, apoE4/2, and apoE4/4 phenotypes) and those of carrying apoE3
      isoform without apoE4 isoform (apoE3/3 phenotypes and apoE2/3 phenotypes). The
      concentrations of serum hsCRP, sVCAM-1, sICAM-1, and sE-selectin were measured in
      211 subjects from Finnish low-HDL families and in 157 normolipidemic subjects.
      The subjects with apoE4 isoform had lower concentrations of serum hsCRP both in
      low-HDL family members (p < 0.05) and in normolipidemic subjects (p < 0.01). The
      differences in serum CRP values remained significant after adjustment for age,
      BMI, smoking status, hypertension, gender, lipoprotein variables, and family
      number. We conclude that apoE phenotype has a strong influence on serum CRP
      values.

PMID- 16951485
TI  - Expression of TNF-alpha and related signaling molecules in the peripheral blood
      mononuclear cells of rheumatoid arthritis patients.
AB  - We examined the role of tumor necrosis factor (TNF-alpha) and its related
      signaling intermediates leading to apoptosis/proliferation in the peripheral
      blood mononuclear cells (PBMCs) of RA patients. The constitutive expression of
      mRNA for TNF-alpha receptors (TNFR-I and TNFR-II) and the adapter molecules, such
      as the TNF receptor-associated death domain protein (TRADD), Fas-associated death
      domain protein (FADD), receptor interacting protein (RIP), and TNF receptor
      associated factor 2 (TRAF-2) were analyzed by reverse transcriptase-PCR (RT-PCR)
      in PBMCs from control and RA cases. PBMCs of RA patients showed a significant
      increase in TNF-alpha and TNFR-I expression as compared with that from control
      subjects along with significantly increased constitutive expression of TRADD,
      RIP, and TRAF-2 mRNA. There was a decrease in expression of FADD in RA patients,
      but the difference was not significant as compared to controls. These data
      suggested enhanced signaling by the TNFR-I-TRADD-RIP-TRAF-2 pathway and
      suppressed signaling by the TNFR-I-TRADD-FADD pathway in PBMCs of RA patients.
      However, the regulatory mechanisms for TNF-alpha induced signaling may not be
      explained only by these pathways.

PMID- 16951486
TI  - Nitric oxide levels in patients with psoriasis treated with methotrexate.
AB  - Psoriasis is a chronic, recurrent, inflammatory, and hyperproliferative disease.
      Recently there have been studies regarding increases in the levels of NO in
      inflammatory dermatoses including psoriasis. In this study, 22 patients with
      psoriasis were scored with PASI (psoriasis area and severity index) and the
      levels of serum nitrite-nitrate were evaluated before and after therapy with
      methotrexate (Mtx). The results were compared with age- and sex-matched healthy
      volunteers. The relation of the results with the clinical severity and the
      cumulative Mtx dose were also evaluated. The serum levels of nitrite-nitrate of
      the psoriatic patients with active lesions were found to be significantly higher
      than the levels of the healthy volunteers and the patients after therapy. The
      elevated nitrite-nitrate serum levels in the inflammatory period may suggest the
      possible role of this mediator in the etiopathogenesis of psoriasis and the
      potential future use of NO inhibitors in the treatment of psoriasis.

PMID- 16951487
TI  - Unexpected smoking-linked high MMP-9 in induced sputum of hazardous dust-exposed
      workers.
AB  - We investigated whether metalloproteinase-9 (MMP-9) values in induced sputum (IS)
      and pulmonary function tests can serve as a marker of damage and intensity of
      exposure to hazardous dust. Thirty-nine factory employees (28 workers exposed to
      metal particles and 11 supposedly nonexposed office workers) underwent IS
      induction. Samples were processed by conventional methods within 2 hours. The
      proportion of particles with diameters of 0-2 mu in IS samples was significantly
      higher in nonexposed than exposed workers and in smoker compared to nonsmoker
      workers. MMP-9 and TIMP-1 levels were similar for both groups. A linear
      regression model for MMP-9 based on exposure, smoking habits, and proportion of
      particles < 5 mu revealed a positive correlation between each of the explanatory
      variables and MMP-9 values. MMP-9 may serve as a marker for pulmonary injury.

PMID- 16951488
TI  - Testicular nitric oxide and thiobarbituric acid reactive substances levels in
      obstructive azoospermia: a possible role in pathophysiology of infertility.
AB  - OBJECTIVE: The aim of the study is to evaluate the levels of nitrite/nitrate and
      thiobarbituric acid reactive substances (TBARS) and their relationship with
      seminal parameters in experimental obstructive azoospermic rats to explain the
      possible mechanism of impaired sperm quality in obstructive azoospermia. METHODS:
      A total of 10 male Spraque-Dawley rats underwent bilateral vas resection and
      ligation (Group-1 = vasectomy group). The findings were compared with control
      group (Group-2 = sham group, n = 10). Animals were sacrificed 8 weeks after
      surgery. Testes were removed and used for the evaluation of nitrate/nitrite and
      TBARS levels and for histology. Epididymal-aspirated seminal plasma was used for
      semen count and morphological analysis according to the Kruger criteria. RESULTS:
      Testicular tissue nitrate/nitrite and TBARS levels were 35.7 +/- 3.1 micromol/g
      protein and 3.7 +/- 0.1 nmol/g protein in Group-1, and 19.3 +/- 0.7 micromol/g
      protein and 3.1 +/- 0.1 nmol/g protein in Group-2, respectively. Both parameters
      showed statistical differences between the two groups. Testicular tissue
      nitrate/nitrite and TBARS levels showed negative and statistically significant
      correlations with sperm motility and morphology. CONCLUSIONS: The present study
      showed that testicular nitrate/nitrite and TBARS levels were increased in
      obstructive azoospermia. For that reason, we concluded that antioxidant treatment
      can be recommended to patients before sperm extraction for artificial
      reproduction due to obstructive infertility after vasectomy reversal.

PMID- 16951489
TI  - Genetic analysis of MEFV gene pyrin domain in patients with Behcet's disease.
AB  - OBJECTIVES: Behcet's disease (BD) is a systemic vasculitis with recurrent oral
      and genital ulcers and uveitis. MEFV gene, which is the main factor in familial
      Mediterranean fever (FMF), is also reported to be a susceptibility gene for BD.
      The pyrin domain of MEFV gene is a member of death-domain superfamily and has
      been proposed to regulate inflammatory signaling in myeloid cells. This study was
      designed to determine if mutations in pyrin domain of MEFV gene are involved in
      BD. METHODS: We analyzed the pyrin domain of MEFV gene in 54 Turkish patients
      with BD by PCR-analysis and direct sequencing. RESULTS: Neither deletion or
      insertion mutations nor point mutations in pyrin domain were found in any
      patient. CONCLUSION: Although pyrin gene mutations have been reported in patients
      with BD, pyrin domain is not mutated. However, alterations in other regions of
      MEFV gene and interaction between pyrin domains are needed to be further
      investigated.

PMID- 16951490
TI  - Circulating sCD138 and some angiogenesis-involved cytokines help to anticipate
      the disease progression of early-stage B-cell chronic lymphocytic leukemia.
AB  - Syndecan-1 (CD138) is a transmembrane heparin sulfate proteoglycan expressed on
      distinct stages of differentiation of B-lymphoid cells. Its prognostic value in B
      cell chronic lymphocytic leukemia (B-CLL) has not been evaluated so far. The
      serum concentration of sCD138 and some angiogenesis-involved cytokines: vascular
      endothelial growth factor (VEGF), basis fibroblast growth factor (bFGF), and
      endostatin were studied in 52 previously untreated patients with B-CLL. We found
      that bFGF and sCD138 levels were significantly higher in B-CLL patients than in
      controls. In patients with sCD138 level or endostatin level below the median
      value the lymphocyte count was higher than in patients with serum level of those
      cytokines above the median value. In patients with progressive disease bFGF level
      was significantly higher and sCD138 level significantly lower than in patients
      with stable one. Moreover, high sCD138 level was associated with longer
      lymphocyte doubling-free survival, and, on the limit of statistical significance,
      a high endostatin level was associated with shorter progression-free survival. We
      conclude that serum sCD138 level is increased in early stage B-CLL patients and
      may have a positive prognostic value as to the dynamics of the disease.

PMID- 16951491
TI  - Systemic and local CC chemokines production in a murine model of Listeria
      monocytogenes infection.
AB  - Repeated intragastric inoculation of Listeria monocytogenes into BALB/c mice
      resulted in prolonged bacteraemia and severe hepatic infection. Bacteria could
      also be isolated from the brain tissue of all experimental mice. During the
      inflammatory process, chemokine concentrations typically increased at the local
      site in comparison to the systemic level. The liver-to-serum ratio was more
      pronounced in the case of macrophage inflammatory protein 1 alpha (MIP-1 alpha),
      suggesting its role in the inflammatory response in the liver. The ratio of brain
      to-serum concentration of monocyte chemoattractant protein 1 (MCP-1) remained the
      same as in the control animals, while it was lower in the infected mice, both in
      the case MIP-1alpha and in the case of regulated on activation, normal T cell
      expressed and secreted (RANTES). This is in correlation with slight inflammatory
      infiltrates found in the brain tissue early in infection.

PMID- 16951492
TI  - Constitutive expression of functionally active protease-activated receptors 1 and
      2 in human conjunctival epithelial cells.
AB  - Protease-activated receptors (PARs) are G-protein-coupled receptors which
      initiate inflammatory responses when activated by specific serine proteases. This
      study was conducted to examine whether human conjunctival epithelial cells
      (HCECs) express functionally active PAR1 and PAR2 using Chang conjunctival
      epithelial cells as in vitro model. We performed RT-PCR and immunofluorescence
      analyses to determine the expression of PAR1 and PAR2, and monitored the
      production of IL-6 after activating HCECs with PAR1 activating agents (thrombin
      or TFLLRN) or PAR2 activating agents (tryptase, trypsin, or SLIGKV). The results
      show that HCECs constitutively express PAR1 and PAR2 mRNA and proteins, and
      produce significant amounts of IL-6 when incubated with specific PAR-activating
      enzymes or agonist peptides. Thrombin- and tryptase-induced HCEC activation was
      blocked by PAR1 and PAR2 neutralizing antibodies, respectively, and by specific
      enzyme inhibitors. The constitutive expression of PAR1 and PAR2, and their
      activation by thrombin and tryptase, respectively, may have important
      implications in ocular inflammation.

PMID- 16951494
TI  - Role of interleukin-18 in modulation of oral carcinoma cell proliferation.
AB  - Interleukin-18 (IL-18), a proinflammatory cytokine, is produced by oral epithelia
      and carcinoma cells and implicated in tumor regression. Since its direct
      biological effect on oral cancer cells is not well defined, in this study, we
      employed a KB cell line to test IL-18 activity. Recombinant human IL-18
      significantly inhibited KB cell proliferation in a dose-dependent fashion (P <
      .05) without increasing cytotoxicity. Analysis of its mode of action showed that
      IL-18 induced cell cycle arrest in the S phase; however, it did not trigger
      apoptotic cell death. Findings in this study indicate that the suppression of KB
      cell proliferation was attributed to the modulation of cell cycle progression,
      providing a new role of this cytokine in antitumor mechanisms.

PMID- 16951493
TI  - Suppression of carrageenan- and collagen II-induced inflammation in mice by
      geranium oil.
AB  - To obtain experimental evidence on the therapeutic efficacy of essential oils in
      aromatherapy for inflammatory diseases, we examined the effects of geranium oil
      on carrageenan-induced and collagen II-induced inflammation in mice, to assess
      acute and chronic anti-inflammatory activities of the oil. Single intraperitoneal
      injection of 5 mu L of geranium oil clearly suppressed the carrageenan-induced
      footpaw edema and increase in tissue myeloperoxidase activity, and repeated
      administration of the oil suppressed collagen-induced arthritis. These results
      revealed that geranium oil suppressed both acute and chronic inflammatory
      responses in mice.

PMID- 16951495
TI  - Comparison of effects of smoking and smokeless tobacco "Maras powder" use on
      humoral immune system parameters.
AB  - BACKGROUND: The aim of this study is to assess the impacts of "Maras powder" and
      cigarette smoking on the parameters of the humoral immune system. MATERIAL AND
      METHODS: One hundred seventy seven subjects were included in the study. The IgA,
      IgG, IgM, C3 and C4 levels were detected via nephelometric method. RESULTS: In
      1.4% of the control group IgM levels were below normal where it was 10.8% and
      18.6% in Maras powder group and in cigarette smoking group respectively. The IgM
      levels of both groups were significantly lower compared to the control group (P <
      .05). Nonetheless, the IgE levels of Maras powder group and smoking group were
      found to be remarkably higher compared to the control group (P < .01).
      CONCLUSION: Effects of Maras powder on humoral immune response were found to be
      similar to that of smoking.

PMID- 16951496
TI  - Regulated spatial distribution of cyclooxygenases and lipoxygenases in Crohn's
      ulcer.
AB  - BACKGROUND AND AIMS: Arachidonic acid metabolism actively participates in the
      initiation, climaxing, and resolution phases of inflammation, and its close
      connection with inflammatory bowel diseases has been only recently discovered. We
      aimed to clarify the role of different arachidonic pathways and the
      interrelationships between them in Crohn's disease. METHODS: Seventeen specimens
      of Crohn's disease dated between 2003/1/1 and 2005/1/1 were collected and
      underwent immunohistochemical analyses with cylcooxygenase 1, cyclooxygenase 2, 5
      lipoxygenase, and 15-lipoxygenase-1 antibodies. RESULTS: (1) The spatial
      distribution of the three leading enzymes in arachidonic acid pathway-
      cyclooxygenase 2, 5-lipoxygenase, and 15-lipoxygenase-1--followed sequential
      arrangement in Crohn's ulcer: neutrophils highly expressing 5-lipoxygenase were
      in the utmost surface which bordered the band of cyclooxygenase-2 expression that
      is located just beneath it, and in the lower layers and below the granulation
      region were eosinophils carrying 15-lipoxygeanse-1. (2) Cyclooxygenase-2 and 15
      Lipoxygenase-1-positive cells formed two barrier-like structures that possibly
      inhibited neutrophil infiltration. CONCLUSION: The regulated distribution
      indicated coordinated interplay between inflammatory cells and parenchymal cells,
      between arachidonic acid pathways, and between innate and adaptive immunity; and
      the barrier-like structures indicated protective roles for cyclooxygenase 2 and
      15-Lipoxygenase-1 in Crohn's disease.

PMID- 16951497
TI  - MEF2A gene and susceptibility to coronary artery disease in the Chinese people.
AB  - OBJECTIVE: To explore MEF2A gene and susceptibility to coronary artery disease in
      the Chinese. METHODS: One hundred seventy-five coronary artery disease (CAD)
      patients and 228 normal subjects were recruited and their blood samples were
      amplified to detect sequences of all 11 exons of MEF2A gene by PCR. Single-strand
      conformational polymorphism (SSCP) analysis was used to detect the mutation. The
      amplified products were purified and sequenced. RESULTS: The tri-nucleotide (CAG)
      length polymorphism in the last coding exon of MEF2A in the Chinese was revealed
      and 4 of the 175 (2.3%) CAD samples containing 4 prolines were due to one proline
      deletion in MEF2A gene. But all the 228 normal subjects contained 5 prolines. The
      mutation in both 175 CAD samples and 228 normal subjects was not found in other
      exons. CONCLUSION: The deletion mutation in exon 11 in MEF2A gene may be related
      to CAD susceptibility in the Chinese population.

PMID- 16951498
TI  - [Cloning and expression of the succinate dehydrogenase iron-sulfur protein of
      Schistosoma japonicum Chinese strain in E. coli].
AB  - OBJECTIVE: To clone the full-length gene encoding succinate dehydrogenase iron
      sulfur protein of Schistosoma japonicum (SjSDISP) Chinese strain and express it
      in Escherichia coli. METHODS: According to the published incomplete EST
      (BU804141) of SjSDISP and the sequence of multiclone sites of lambda gt11 vector,
      2 pairs of primers were designed and synthesized. Then the 3' and 5'ends of the
      EST of the SjSDISP from adult Schistosoma japonicum cDNA library were amplified
      by anchored PCR. After sequencing, a full-length cDNA sequence of the SjSDISP was
      obtained, and then it was cloned into prokaryotic expression vector pGEX-4T-1.
      Identified by agarosed gel electrophoresis, endonucleases digestion and PCR, the
      resultant recombinant plasmid was used for the expression under the temperature
      dependent condition and Western blot analysis. RESULTS: A 1,071 bp sequence was
      obtained. Sequence analysis showed that the fragment contained a complete open
      reading frame (ORF), encoding 278 amino acid residues. This target fragment was
      cloned into the prokaryotic expression vector pGEX-4T-1, and expressed in
      Escherichia coli. SDS-PAGE revealed that the molecular weight of the expressed
      fusion recombinant product was 56 kD. Western blot showed that the recombinant
      protein was recognized by polyclonal rabbit antiserum immunized with Schistosoma
      japonicum adult worm antigen. CONCLUSION: Cloning of the full-length gene
      encoding SjSDISP and its bacterial expression were successfully done.

PMID- 16951499
TI  - [Effect of growth inhibition of the secretory protein SPLUNC1 on Pseudomonas
      aeruginosa].
AB  - OBJECTIVE: To express the recombinant SPLUNC1 protein in HNE1 cells and to study
      its function of bactericidal and binding to lipopolysaccharide (LPS). METHODS:
      Full length of SPLUNC1 gene was cloned into pCMV-tag4A vector and stably
      transfected into HNE1 cell lines, the supernatant of cell cultures was collected.
      After being treated with the supernatant, the Pseudomonas aeruginosa was seeded
      to LB soft agar plate, and the bacteria clones were counted and analyzed. For in
      vitro LPS binding assay, LPS was coated to 96-well plates. We incubated in the
      plate with SPLUNC1 protein, and detected the binded SPLUNC1 protein by ELISA.
      Incubating the FITC-LPS with the SPLUNC1 stably transfected or control cells, the
      intracellular intensity of fluorescence was observed under the fluorescence
      microscope. RESULTS: SPLUNC1 inhibited the bacteria clone formation obviously.
      Although the binding efficiency of LPS and SPLUNC1 in vitro was very low, more
      FITC-LPS entered into the SPLUNC1 stably transfected cells. CONCLUSION: SPLUNC1
      can inhibit the growth of Pseudomonas aeruginosa and bind LPS, and play an
      important defensive role in innate immunity of the upper airway.

PMID- 16951500
TI  - [Mechanism of migration in CNE2 cells promoted by EBV-LMP1].
AB  - OBJECTIVE: To investigate the mechanism of migration phenotype change induced by
      EBV-LMP1 in nasopharyngeal carcinoma (NPC) cell line CNE2. METHODS: Retroviruses
      RV-LNSX, RV-LMP1, and RV-LMP1(TRADD) prepared previously were used to infect CNE2
      cells. After selection with G418, the morphology, the ability of motion and
      migration in extracellular matrix, expression of LMP1 and E-Cadherin in
      transgenic cells were observed or detected. Meanwhile, pEcad-luc was respectively
      co-transfected with pLNSX, pLNSX-LMP1, and pLNSX-LMP1(TRADD), to examine the
      effect of LMP1 on the transcriptional activity of E-Cadherin promoter in 293
      cells. RESULTS: Compared with CNE2 and CNE2-LNSX cells, CNE2-LMP1 cells
      morphologically changed from typical epithelial appearance to long-spindle
      fibroblastic morphology with the concomitant loss of cell-to-cell contact, and
      relative migration of CNE2-LMP1 cells obviously increased (n=3, P< 0.05), while
      the expression of E-Cadherin was negative in CNE2-LMP1 cells. The transcriptional
      activity of E-Cadherin promoter and the expression of E-Cadherin was suppressed
      by LMP1, and the level of suppression was correlated with the concentration of
      pLNSX-LMP1 (0.2,0.6 and 1.0 microg). LMP1(TRADD) didn't induce the changes of
      morphology and migration phenotype, nor suppress the transcriptional activity of
      E-Cadherin promoter and the expression of E-Cadherin in CNE2 cells. CONCLUSION:
      EBV-LMP1 promotes the migration and down-regulates the expression of E-Cadherin
      in CNE2 cells. The mechanism is that EBV-LMP1 suppresses the transcriptional
      activity of E-Cadherin promoter. TRADD of carboxyl terminus of LMP1 may be the
      main active domain to promote the migration in NPC cells.

PMID- 16951501
TI  - [Genetic relationships between Ewenki minority in Inner Mongolia and other 14
      groups].
AB  - OBJECTIVE: To study the STR genetic structure of an Ewenki Ethnic minority Group
      of Inner Mongolia, and analyze the genetic relationship among Ewenki and other 14
      groups. METHODS: Genetic distribution for 9 STR loci (D3S1358, vWA, FGA, TH01,
      TPOX, CSF1PO, D5S818, D13S317, and D7S820) were determined based on gene scan
      marked by fluorescence. Principle component analysis was performed using SPSS.
      RESULTS: Sixty-four alleles and 158 genotypes were observed in 90 unrelated
      Ewenki individuals. The corresponding gene frequency and genotype frequency was
      0.0056 to 0.4722 and 0.0111 to 0.3, respectively. The expected and observed
      genotype frequency of the 9 STR loci were in accordance with the Hardy-Weinberg
      equilibrium (P>0.05). The principle component analysis showed that Ewenki
      clustered with groups of Mongolian and Tujue language branch. CONCLUSION: Nine of
      the STR genetic structure of an Ewenki Ethnic minority Group of Inner Mongolia
      were obtained. Those ethnic groups in subfamilies of Altaic language family
      clustered as their geographical location and those with close genetic
      relationships use similar language.

PMID- 16951502
TI  - [MICA*008/A5.1 allele and HCMV infection in kidney transplanted donees of Hunan
      Han nationality].
AB  - OBJECTIVE: To investigate the relationship between MICA*008/A5.1 allele and human
      cytomegalovirus (HCMV) infection in kidney transplanted donees of Hunan Han
      nationality. METHODS: The MICA*008/A5.1 allele based on 91 kidney transplanted
      donees and 81 unrelated normal individuals of Han nationality in Hunan Province
      were analyzed by PCR/SSP assay. At the same time, anti-HCMV antibody IgM was
      detected in the serum by ELISA method. RESULTS: The positive rate of
      MICA*008/A5.1 allele was significantly higher in the control group (56.79%) than
      that in the kidney transplanted donee group (34.07%) (P <0.05). The infection
      rate of HCMV in those individuals whose genotype was MICA*008/A5.1 (-) was
      significantly higher than that in the MICA*008/A5.1(+). CONCLUSION: The
      individual whose genotype is MICA*008/A5.1 (+) is not liable to HCMV infection,
      but the individual whose genotype is MICA*008/A5.1 (-) is liable to HCMV
      infection.

PMID- 16951503
TI  - [Effects of xipayi mouth rinse on the DNA synthesis and change of cell cycles of
      human gingival fibroblast induced by lipopolysaccharide].
AB  - OBJECTIVE: To observe the effects of xipayi mouth rinse on the DNA synthesis and
      change of cell cycles of human gingival fibroblast (HGF) induced by
      lipopolysaccharide(LPS). METHODS: HGF was stimulated with LPS at 25 mg/L. Flow
      cytometry was used to examine the effect of xipayi mouth rinse at 25 mg/L on the
      DNA synthesis and change of HGF cell cycles. RESULTS: The percentage of HGF in G(
      1) phase increased after the cells were induced by LPS, while the percentage of
      HGF in S phase decreased. Xipayi mouth rinse could ameliorate this phenomenon.
      CONCLUSION: Xipayi mouth rinse can significantly ameliorate the inhibitory effect
      of LPS on the proliferation of HGF, suggesting the anti-inflammatory effect of
      xipayi mouth rinse in the treatment and prevention of periodontal diseases.

PMID- 16951504
TI  - [Establishment of 2-dimensional gel electrophoresis map and analysis of
      proteomics from human nasal polyps].
AB  - OBJECTIVE: To establish 2-dimensional polyacrylamide gel electrophoresis (2-DE)
      map from human nasal polyps and normal nasal mucosa, and to identify differential
      expression proteins of 2-DE map. METHODS: Samples of nasal polyps and nasal
      mucosa (each sample group containing 7 cases) were obtained. The total proteins
      were extracted and separated by immobilized pH gradient (IPG)-based 2-DE. The
      silver-stained 2-DE was scanned with digital Imagescanner and analyzed with
      ImageMaster 2-DE Elite 4.01 software. To obtain peptide mass fingerprint (PMF) of
      differential protein spots, matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF-MS) was used. The PMF was searched in Swiss
      Prot and TreMBL database by Pept-Ident software, to identify differential
      expression proteins. RESULTS: The well-resolved, reproducible 2-DE maps of nasal
      polyps and nasal mucosa were established. For the polyps tissues, the average
      proteins spot of three 2-DE maps was 825+/-78; and 682+/-96 spot was matched with
      the average matching rate of 82.7%. The average deviations of matched spot
      position were (1.13+/-0.16) mm in IEF direction and (1.45+/-0.21) mm in SDS-PAGE
      direction, respectively. For the nasal mucosa tissues, the average proteins spot
      of three 2-DE maps was 936+/-62; and 821+/-78 spots were matched with the average
      matching rate of 87.7%. After comparing the 2-DE maps of nasal polyps and nasal
      mucosa tissues, the protein spots were 1,458 and 1,617 respectively; and 1,026
      protein spots were matched. Forty differential expression protein spots were
      incised from silver staining gel randomly and digested in the gel by TPCK
      Trypsin. Thirty-four PMFs were obtained by MALDI-TOF-MS and 24 differential
      proteins were identified. CONCLUSION: The well-resolved, reproducible 2-DE maps
      of human nasal polyps and nasal mucosa have been successfully established.
      Certain differential proteins related to the pathogenesis of human nasal polyps
      are identified.

PMID- 16951505
TI  - [Inhibition of human macrophage-derived foam cell differentiation by blocking
      Kv1.3 and Kir2.1 channels].
AB  - OBJECTIVE: To investigate the expression of Kv1.3 and Kir2.1 during human
      monocyte-derived macrophages differentiation into foam cells and their function
      in foam cells formation. METHODS: The human macrophage-derived foam cells were
      obtained by incubating macrophages with ox-LDL (30 mg/L) for 60 h. The expression
      of Kv1.3 and Kir2.1 channels were examined by immunocytochemistry, RT-PCR and
      Western blot. Effects of channel blockers (rMargatoxin and BaCl2) on the cellular
      cholesterol metabolism were studied by measuring the cellular contents of total
      cholesterol (TC), free cholesterol (FC), and cholesterol ester (CE) in the
      presence or absence of the channel blockers. RESULTS: After incubating
      macrophages with 30 mg/L ox-LDL for 60 h, the cellular contents of TC, FC and CE
      were markedly increased and the ratio of CE/TC was raised from (14.4+/-6.8)% to
      (57.9+/-3.5)% (P<0.05), which indicated that the cells had differentiated into
      foam cells. The expression of Kv1.3 and Kir2.1 channels appeared no obvious
      difference when differentiating into foam cells (P>0.05); After being blocked
      specifically (rMargatoxin: 0.1, 10 nmol/L; BaC(12): 75, 125 micromol/L), the
      cellular contents of TC and CE were markedly reduced without exception and the
      ratios of CE/TC were all less than 50% (P<0.05). CONCLUSION: Both Kv1.3 and
      Kir2.1 channels play a critical role in differentiation of macrophages into foam
      cells and blockage of corresponding potassium channels would prevent the
      formation of the foam cells.

PMID- 16951506
TI  - [Inhibition of islet beta cell apoptosis and prevention diabetes by subcutaneous
      administration of insulin in NOD mice].
AB  - OBJECTIVE: To investigate the effects of subcutaneous administration of insulin
      on insulitis,beta cell apoptosis and diabetes in non-obese diabetic (NOD) mice,
      and to explore the mechanism of immune tolerance induced by insulin. METHODS:
      Sixty female NOD mice were randomly divided into insulin group (n=32) and
      phosphate buffered saline (PBS) group (PBS group, n=28). Insulin was
      subcutaneously injected with humulin N (60 microL, 6U)+IFA (60 microL) at 4, 12,
      20, and 28 weeks respectively, while the PBS group received PBS (60 microL) + IFA
      (60 microL). Insulitis and beta cell apoptosis of islets were observed at 12
      weeks. IL-4 and IFN-gamma in the sera were measured by enzyme linked
      immunosorbent assay (ELISA). The expression levels of I-Abeta(g7), IL-4, IFN
      gamma, IL-1beta, and Fas mRNA of islets were measured by reverse transcription
      polymerase chain reaction (RT-PCR) at 12 weeks. RESULTS: The incidences in the
      insulin group were significantly lower than those in the PBS group (21.4% vs
      71.4% at 30 weeks, 28.6% vs 85.7% at 52 weeks, P<0.05). The insulitis scores in
      the insulin group were lower than those in the PBS group, but there was no
      statistical significance. Fas expression on islets and apoptotic beta cell rates
      in the insulin group were lower than those in the PBS group (P<0.05). In the
      insulin group, serum IL-4 levels were higher, but IFN-gamma levels were lower
      than those in the PBS group (P<0.05). The levels of I-Abeta g7, IFN-gamma, IL
      1beta and Fas mRNA transcription in islets were lower in insulin group, but IL-4
      mRNA levels were higher than those in the PBS group (P<0.05). CONCLUSION: The
      specific autoantigen insulin may induce immune tolerance and prevent diabetes in
      NOD mice, but it can't block the progression of insulitis. Subcutaneous
      administration of insulin can induce the regulatory T cells, and make Th1 to Th2
      cytokine shifts in system and islets, thus preventing the Fas-mediated beta-cell
      apoptosis and diabetes.

PMID- 16951507
TI  - [Biological stability analysis of QY1 pluripotential mesenchymal stem cell line
      from Sprague Dawley rat bone marrow].
AB  - OBJECTIVE: To explore the optimal culture conditions in vitro and the biological
      characterizations of the QY1 pluripotential mesenchymal stem cell (MSC) line from
      Sprague-Dawley rat bone marrow and to analyze the biological stability of this
      MSC line so as to provide an ideal cell model for the further differentiation and
      actual application. METHODS: The methods and technologies of cell biology and
      stem cell tissue engineering were used to purify MSCs. We determined the effects
      of morphology of cell proliferation, the time of change medium, growth curves,
      doubling time, adhesive rates, chromosome, culture conditions, and repeated frost
      on the biological characterizations of MSCs. RESULTS: The cells had a
      fibroblastic-like morphology and were well spread out; 80% - 90% cells became
      confluent between 10 and 12 days in primary culture. The growth curves of Passage
      1, 3, 10, and 20 were quite similar (P>0.05). The doubling time of passage 1, 3,
      10, and 20 were 34.2, 33.9, 31.8, and 30.6 hours, respectively. The adhesive
      rates of Passage 1, 3, 10, and 20 were very much similar (P>0.05) and about 89%
      subcultured cells adhered to the wall in 10 hours. The most appropriate
      concentration of serum was 20% and the most appropriate concentration of cell
      number was 8 x 10(4)/mL. The cells of Passage 8 showed light red cytoplasm and
      heavy blue nuclear stained by Giemsa staining. The chromosomes of Passage 8 and
      20 were normal in appearance and their karyotypes were 42, XY. The cells were
      resuscitable after repeated frozen, and more than 85% cells were alive. The cells
      had been continuously cultured for more than 10 months so far. CONCLUSION: The
      QY1 MSCs line from Sprague-Dawley rat bone marrow is a purified cell line, which
      can maintain its undifferentiation and the stable biological characterizations
      for the long term.

PMID- 16951508
TI  - [Effects of astragalus polysaccharides-chitosan/polylactic acid scaffolds and
      bone marrow stem cells on repairing supra-alveolar periodontal defects in dogs].
AB  - OBJECTIVE: To explore the effect of astragalus polysaccharides
      chitosan/polylactic acid (AP-C/PLA) scaffolds and bone marrow stem cells (BMSCs)
      on periodontal regeneration of experimentally horizontal periodontal defects in
      dogs. METHODS: Dog BMSCs were isolated from the bone marrow and then cultured in
      a conditioned medium to be induced for osteogenesis. The expressions of Type I
      collagen and alkaline phosphatase (ALP) were examined by immunohistochemistry and
      histochemistry in the induced BMSCs, respectively. The BMSCs were harvested and
      implanted with astragalus polysaccharides-chitosan/polylactic acid (AP-C/PLA) and
      chitosan/polylactic acid (C/PLA) scaffolds. Horizontal alveolar bone defects (5
      mm depth, 2 mm width) were produced surgically in the buccal side of the
      mandibular premolar 3 and 4 of the 10 dogs. The defects were randomly repaired
      with a cell-scaffold construction (10 teeth per group): root planning only
      (surgical control), AP-C/PLA with a conditioned medium (medium control), C/PLA
      with BMSCs (scaffolds control), and AP-C/PLA with BMSCs (experimental group) .
      The dogs were killed at 4 weeks and 8 weeks after the surgery, and block sections
      of the defects were collected for the histologic and histometric analysis.
      RESULTS: BMSCs induced in vitro exhibited an osteogenic phenotype with expressing
      Type I collagen and ALP histologically. The bone nodule structure was observed in
      the experimental group 4 weeks postsurgically. The engineered bone became more
      mature,similar to the native bone 8 weeks postsurgically. The amount of new bone
      regeneration and the rate of new bone filling to the defect height of the
      experimental group were significantly different from those of the surgical
      control, medium control, and scaffolds control [(2.90+/-0.41) mm vs (0.83+/-0.30)
      mm, (1.46+/-0.55) mm, (2.67+/-0.26) mm; 57.46% vs 15.68 %, 30.13%, 51.87%)]
      (P<0.01, P<0.01, P<0.05). CONCLUSION: Astragalus polysaccharides can promote the
      new bone formation on the periodontal defects. The technology of tissue
      engineering with AP-C/PLA scaffolds and induced BMSCs may contribute to the
      periodontal regeneration.

PMID- 16951509
TI  - [Effect of continuously compressive pressure on the expression of RANKL mRNA in
      human periodontal ligament cells in vitro].
AB  - OBJECTIVE: To determine the effect of continuously compressive pressure (CCP) on
      the expression of receptor activator of nuclear factor kappa B ligand (RANKL) in
      human periodontal ligament cells (HPDLCs) and to investigate the role of RANKL in
      alveolar bone rebuilding during orthodontic tooth movement. METHODS: The primary
      HPDLCs were isolated from human periodontal ligament by explanting enzymatic
      digestion with trypsin and collagenase to establish a pressure model. Top-bottom
      axial pressures (1, 2, and 3 g/cm(2)) were laid on HPDLCs for 0.5, 1.5, 6, 12,
      24, and 48 h, respectively. The RANKL expression was identified by the reverse
      transcription-polymerase chain reaction (RT-PCR) at the mRNA level. RESULTS: The
      expression of RANKL mRNA significantly increased in a time-dependent manner
      (P<0.01), so did the value of pressure, especially in the 2 g/cm(2) group
      (P<0.05). CONCLUSION: CCP can up-regulate the expression of RANKL mRNA in human
      periodontal ligament cells.

PMID- 16951510
TI  - [Expression of Ang2 and Tie2 and their relation with the angiogenesis of
      hepatocellular carcinoma in rats].
AB  - OBJECTIVE: To investigate the relationship between the expression of Ang2, Tie2
      and the angiogenesis of hepatocellular carcinoma in rats. METHODS: Thirty-eight
      healthy male rats were randomly divided into 3 groups: 5 rats in the control
      group; 25 rats in the experimental group were equally divided into 5-day, 10-day,
      15-day, 20-day, and 25-day groups; the other 8 rats were used as the supplement
      of the experimental group. An allogenic transplanted rat model of CBRH-7919
      hepatocellular carcinoma in situ was established by immunosuppression. The
      expressions of Ang2 and Tie2 were detected by immunohistochemical staining in
      cancerous tissues of different developmental stages and liver tissues of the
      control group. At the same time, microvessel density was determined by anti-CD31
      immunohistochemical staining. RESULTS: CBRH-7919 hepatocellular carcinoma models
      were successfully set up in 24 rats. The expression level of Ang2 and Tie2 in
      cancerous tissues was much higher than that of liver tissues of the control group
      (P <0.05). The overexpression of Ang2 was pristine and continuous in different
      developmental stages. The expressions of Ang2 and Tie2 positively correlated with
      microvessal density in hepatocellular carcinoma (P<0.05). CONCLUSION: The up
      regulation of Ang2 and Tie2 may play important roles in the angiogenesis of
      hepatocellular carcinoma. Ang2 may participate in the start of angiogenesis of
      hepatocellular carcinoma.

PMID- 16951511
TI  - [Inhibitory effect of resveratrol on the proliferation of synoviocytes in
      rheumatoid arthritis and its mechanism in vitro].
AB  - OBJECTIVE: To investigate the effect of resveratrol on the proliferation and
      apoptosis of synoviocytes in patients with rheumatoid arthritis (RA) in vitro and
      explore its mechanism. METHODS: The levels of cell proliferation of synoviocytes
      in RA after 24 h treated with different concentrations of resveratrol were
      measured by monotetrazolium colourmetric assay method. The percentages of
      synoviocytes apoptosis in RA after 24 h treated with different concentrations of
      resveratrol were tested by TUNEL and flow cytometry. The relative activities of
      caspase-3 were determined by colorimetric assay after 4, 8, 12, 18, and 24 h
      treated with resveratrol (200 micromol/L) and 12 h treated with different
      concentrations of resveratrol. The cleavages of pro-caspase-3 were analyzed by
      Western blot after 24 h treated with different concentrations of resveratrol.
      RESULTS: The levels of cell proliferation of synoviocytes with RA after 24 h
      treated with different concentrations of resveratrol were significantly decreased
      compared with the control group (P<0.01). The percentages of the apoptotic cells
      were increased of resveratrol-treated after 24 h, the apoptosis rates between the
      treated groups and the control group were significantly different (P<0.01). When
      the synoviocytes in RA were treated with 200 micromol/L resveratrol for different
      time respectively, the caspase-3 activity began to rise significantly at 4h,
      reaching the peak at 12 h, and was still much higher than that of the control
      group at 24 h (P<0.01). After the cells were treated with different
      concentrations of resveratrol for 12 h, caspase-3 activity increased in a
      concentration-dependent manner. After synoviocytes in RA were treated with
      different concentrations of resveratrol for 24 h, the expressions of pro-caspase
      3 decreased as the concentration increased, the caspase-3 active fragment P11 (11
      kD) appeared at 100 micromol/L and was increased at 400 micromol/L. CONCLUSION:
      Resveratrol inhibits the proliferation of synoviocytes and induces cell apoptosis
      in rheumatoid arthritis in vitro, which may relate to the activation of caspase
      3.

PMID- 16951512
TI  - [Effect of morphine on dorsal horn projection neurons in neuropathic pain rats].
AB  - OBJECTIVE: To explore the inhibitory effect of spinal topical morphine on the
      dorsal horn projection neurons in nerve-injured rats and its mechanism. METHODS:
      Single-unit activity of dorsal horn projection neurons was recorded in
      anesthetized L(5)/L(6) nerve-ligated rats. Allodynia was determined by a behavior
      test in nerve-injured rats. The evoked neuronal responses to mechanical stimuli
      applied to the receptive field were determined before and after the spinal
      topical application of morphine, bicuculline plus morphine, strychnine plus
      morphine, and both bicuculline and strychnine plus morphine in normal, sham
      operation, and nerve-injured rats. RESULTS: Spinal topical application of 10
      micromol/L morphine significantly inhibited the evoked responses of dorsal horn
      projection neurons in normal, sham, operation and nerve-injured rats. However,
      the inhibitory effect of morphine was significantly reduced in nerve-injured rats
      compared with that in normal and sham operation rats. Furthermore, the topical
      application of 20 micromol/L bicuculline had little effect on the inhibitory
      effect of morphine in nerve-injured rats but it almost abolished the effect of
      morphine in normal and sham operation rats. The glycine receptor antagonist
      strychnine at 4 micromol/L significantly decreased the effect of morphine in
      nerve-injured, normal, and sham operation rats. CONCLUSION: The loss of tonic
      GABAergic inhibition contributes to the reduced inhibitory effect of morphine on
      dorsal horn projection neurons in nerve-injured rats.

PMID- 16951513
TI  - [Effect of hospice care on the quality of life and psychological state of aged
      mortal inpatients].
AB  - OBJECTIVE: To investigate the influence of hospice care on the life quality and
      psychological state of aged mortal inpatients. METHODS: Seventy-six aged patients
      were randomly divided into 2 groups (n=38). The research group was treated with
      hospice care, while the control group was treated with conventional nursing.
      Before and after more than one month of the interference, the quality of life,
      social support, satisfied degree, anxiety, and depression mood were investigated.
      RESULTS: All the indexes, such as total scale of life quality, appetite, spirit,
      sleep, family comprehension and coordination, recognition of cancer, attitude to
      therapy, and facial expression of the mortal inpatients after the interference,
      were raised and higher than those of the controls (P<0.05 or P<0.01). Life
      satisfaction index and the total scale of social support and subjective support,
      utilization ratio of support were raised and higher than those of the controls
      (P<0.05 or P<0.01). The level of anxiety and depression was decreased and lower
      than the control (P<0.05 or P<0.01). CONCLUSION: Hospice care can raise the life
      quality, subjective support, utilization ratio of support and life satisfaction
      of aged mortal inpatients. It could decrease the negative mood, such as anxiety
      and depression and improve the psychological state.

PMID- 16951514
TI  - [Protective effects of granulocyte colony-stimulating factor on acute hepatic
      failure induced by D-galactosamine/lipopolysaccharide in mice].
AB  - OBJECTIVE: To evaluate the protective effect of recombinant human granulocyte
      colony stimulating factor (rhG-CSF) on acute hepatic failure induced by
      galactosamine (D-GalN) and lipopolysaccharide (LPS) in mice, and to explore its
      mechanism. METHODS: The mice were intraperitoneally administered D-GalN (800
      mg/kg) and LPS (10 microg/kg), and then were intraperitoneally injected either
      saline (the control group )or rhG-CSF at 300 microg/kg body weight (the therapy
      group) at 4 h, 2 h and 0 h before the D-GalN/LPS injection. The survival rate of
      the mice was estimated at 24 h after the D-GalN/LPS injection. The degree of
      hepatic injury was evaluated at 6 h after the D-GalN/LPS injection, and the
      levels of TNF-alpha, IFN-gamma, IL-6 and IL-10 mRNA were simultaneously measured
      by semiquantitative RT-PCR. RESULTS: The survival rate of the therapy group was
      significantly higher than that of the control group (68.4% vs 20%, P<0.01). As
      compared with the control group, the degree of liver injury in the therapy group
      significantly decreased (P<0.05), and the levels of TNF-alpha and IFN-gamma mRNA
      in the hepatic tissue also reduced remarkably (P<0.01, respectively), while the
      levels of IL-6 and IL-10 mRNA increased (P<0.01, respectively) at 6 h after the D
      GalN/LPS injection. CONCLUSION: G-CSF can protect the mice from acute hepatic
      failure induced by D-GalN/LPS.

PMID- 16951515
TI  - [Serum HBsAg concentration and HBV replication level in hepatitis B patients with
      positive serum HBsAg and HBeAg].
AB  - OBJECTIVE: To analyze the relationship between serum HBsAg concentration and HBV
      replication level in hepatitis B patients with positive serum HBsAg and HBeAg,
      and to explore the possibility of using serum HBsAg concentration as a marker of
      HBV replication level in hepatitis B patients with positive serum HBeAg. METHODS:
      HBV DNA level and serum HBeAg, HBsAg concentration of 296 patients with positive
      serum HBsAg and HBeAg were quantitatively detected by real-time fluorescence
      quantitative PCR (FQ-PCR) and time-resolved fluoroimmunoassay (TRIFA)
      respectively. HBsAg concentrations were compared among patients with different
      HBV DNA levels, and HBV DNA levels were compared among patients with different
      HBsAg concentrations. The correlation between serum HBsAg concentration and DNA
      replication level were analyzed. The positive, negative predictive values and
      coincidence rates were speculated by various HBsAg concentrations. RESULTS: If
      HBV DNA positive was defined as HBV DNA levels no less than 10(5) copy/mL, then
      228(77.03%) patients were classified as HBV DNA positive. HBsAg concentration was
      positively correlated with HBV DNA replication level, but among groups with
      various DNA replication levels, HBsAg concentration showed no significant
      statistical difference (P>0.05). If the patients were divided into 2 groups,
      HBsAg concentration (180 microg/L) was served as the cutoff level, the DNA
      positive rate of the group with HBsAg concentration no less than 180 microg/L was
      significantly higher than that with HBsAg concentration less than 180 microg/L
      (chi(2)=3.998, P<0.05). DNA positive rates and average DNA levels showed no
      significant statistical differences between the 2 groups, if HBsAg concentrations
      other than 180 microg/L were used as the cutoff level. Positive predictive
      values, negative predictive values and the coincidence rates speculated by
      various HBsAg concentrations as cutoff values did not show any significant
      statistical difference in estimating HBV replication levels. CONCLUSION: To some
      extent, serum HBsAg concentration is related to HBV DNA replication level in
      hepatitis B patients with positive serum HBsAg and HBeAg, but it is not feasible
      to use HBsAg concentration to monitor their HBV replication levels.

PMID- 16951517
TI  - [Oxidative stress and inflammation with angiographic morphology of coronary
      lesions in patients with coronary heart disease].
AB  - OBJECTIVE: To evaluate the role of oxidative stress and inflammation in the
      development of plaque rupture. METHODS: One hundred and ten patients enrolled in
      this study. All patients underwent coronary angiography. It included 85 patients
      with coronary heart disease (CHD) and 25 controls. The angiographic morphology of
      plaques was analyzed. According to the morphologic types of plaque, CHD patients
      were divided into Type I (smooth borders) group (n=31), Type II (irregular
      lesions) group (n=35), and Type III (long lesions) group (n=19). All patients
      were measured of MDA-LDL, hs-CRP, creatine kinase (CK), and MB isoenzyme of CK
      (CK-MB) in the plasma. RESULTS: Plasma MDA-LDL and hs-CRP in the Type II group
      were significantly higher than those in the control group, Type I group, and Type
      III group (P<0.01). The plasma levels of MDA-LDL were not correlated to LDL and
      HDL in patients in Type II group (P>0.05). The plasma levels of MDA-LDL and hs
      CRP had a significant positive correlation in patients in Type II group (r=0.630,
      P<0.01). CONCLUSION: Oxidative stress and inflammation may cause plaque rupture
      in CHD patients. The oxidative stress is likely to either induce or intensify the
      inflammatory action, and may co-affect with inflammation factors to cause or
      accelerate plaque rupture.

PMID- 16951516
TI  - [Anti-oxidant effects of Tongxinluo on ATPase in focal brain ischemia-reperfusion
      rats].
AB  - OBJECTIVE: To explore the effects of Tongxinluo on adenosine triphosphatase
      (ATPase), anti-oxidant enzymes activities, and lipid peroxidation of mitochondria
      or brain homogenate in focal brain ischemia-reperfusion rats. METHODS: The models
      of the focal brain ischemia-reperfusion rats were made by the middle cerebral
      artery occlusion (MCAO). Activities of superoxide dismutase (SOD), glutathione
      peroxidase (GSH-Px), and ATPase and malonaldehyde (MDA) levels of mitochondria or
      brain homogenate were measured by biochemical methods. RESULTS: Tongxinluo
      significantly inhibited the decrease of activities of SOD and the increase of MDA
      levels, but had no difference in GSH-Px in brain homogenate. It also inhibited
      the decrease of activities of SOD, GSH-Px, ATPase, and the increase of MDA levels
      in mitochondria. CONCLUSION: The protective mechanisms of Tongxinluo against
      mitochondrial injuries in focal ischemia-reperfusion rats may be derived from
      reducing lipid peroxides, scavenging free radicals and improving the energy
      metabolism.

PMID- 16951518
TI  - [Effect of atrial pacing on the sleep apnea syndrome in elderly patients].
AB  - OBJECTIVE: To evaluate the efficacy of atrial pacing to increase the heart rate
      during sleep in elderly patients with sleep apnea syndrome. METHODS: Sixteen
      elderly patients with central type or obstructive type sleep apnea received
      permanent atrial-synchronous ventricular pacemakers for symptomatic sinus
      bradycardia were analysed in this study. All patients received polysomnographic
      evaluations for 3 consecutive nights. All patients were evaluated at the base
      line, and then were randomly divided into 2 groups at the first night. In the
      following 2 nights, one group was monitored in spontaneous rhythm model and the
      other in dual-chamber pacing model with atrial overdrive (increasing by 15 beats
      per minute on the basic rate of the mean nocturnal sinus), and then the two
      groups were switched at the third night. The total duration and number of
      episodes of sleep apnea or hypopnea were analyzed, and compared between the two
      models. RESULTS: The mean 24 h sinus rate in the spontaneous rhythm mode was 55+/
      9 beats per minute at the base line, as compared in the 72+/-4 beats per minute
      in the atrial overdrive pacing model. There was statistic significant difference
      between the 2 models (P<0.05). There was no difference in the total duration of
      sleep between spontaneous rhythm model and atrial overdrive pacing model [(322+/
      48) minutes vs (330+/-52) minutes, P>0.05 ]. The hypopnea index reduced from 9+/
      3 in the spontaneous rhythm model to 3+/-3 in the atrial overdrive pacing model
      (P<0.01). The index of apnea and hypopnea was 28+/-21 in the spontaneous rhythm
      model, as compared with 10+/-13 in the atrial overdrive pacing model (P<0.01).
      CONCLUSION: Atrial overdrive pacing can significantly reduce the number of
      episodes of central type or obstructive type sleep apnea, but doesn't decrease
      the total sleep time in elderly patients with sleep apnea syndrome.

PMID- 16951519
TI  - [Relevant factors of microalbuminuria in aged patients with essential
      hypertension].
AB  - OBJECTIVE: To investigate the relationship between microalbuminuria and
      endothelial-dependent relaxing function and atherosclerosis of common carotid
      artery (CCA) in aged patients with essential hypertension (EH). METHODS: Sixty
      four aged EH patients were recruited. According to the albumin excretion rate
      (AER) in the urine measured by immunoturbidimetry, patients were divided into 2
      groups: normoalbuminuria group (NAU group) and microalbuminuria group (MAU
      group). Thirty aged persons without EH were served as the control group. The
      endothelium-dependent relaxing function of blood vessels, intima-media thickness
      (IMT) and the plaque of CCA were measured by color Doppler ultrasound. RESULTS:
      The flow-mediated dilation in the MAU group [(4.98+/-1.35)%] and that in the NAU
      group [(6.31+/-1.14)%] were significantly lower than that in the control group
      [(9.09+/-1.83)%, P<0.05, respectively], especially lower in the MAU group. The
      IMT of CCA in the MAU group [(0.97+/-0.19)mm] and that in the NAU group [(0.86+/
      0.10)mm] were significantly thicker than that in the control group [(0.78+/
      0.13)mm] (P<0.05, respectively), especially thicker in the MAU group. The
      analysis of multiple stepwise regression showed that the microalbuminuria was
      successively related to EDF, the IMT of CCA, the plaque index of CCA, systolic
      blood pressure, etc. CONCLUSION: EDF is impaired, and there is the
      atherosclerosis of CCA in aged patients with EH. Microalbuminuria correlates with
      the decrease of endothelium-dependent relaxing function and the IMT of CCA in
      aged patients with EH.

PMID- 16951520
TI  - [Effect of resveratrol on the cognitive ability of Alzheimeros mice].
AB  - OBJECTIVE: To explore the effect of resveratrol on the cognition of Alzheimer's
      mice (AD) and its mechanism, and to assess its action on the reproduction system.
      METHODS: According to the results of step-down test, 84 Kunming female mice were
      randomly divided into 6 groups: Group A [sham operated+1% CMC-Na (0.01 mL/g)],
      Group B [ovariectomy+D-galactose+1% CMC-Na (0.01 mL/g)], Group C [ovariectomy+D
      galactose+0.05 mg/(kg.d) Diethylstilbestrol], Group D [ovariectomy+D-galactose+15
      mg/(kg.d) Res], and Group E [ovariectomy+D-galactose injected+45 mg/(kg.d) Res],
      and Group F [ovariectomy+D-galactose +135 mg/(kg.d) Res]. Experimental cycle was
      60 days. RESULTS: Resveratrol of every dosage could improve the performance
      records of behavior tests in AD mice,could inhibit the SOD vitality and the MDA
      level both in the serum and in the brain, and could suppress the
      acetylcholinesterase vitality and the bax expression. Resveratrol has no
      endometrial hyperplasia effect. CONCLUSION: Resveratrol can improve the cognitive
      ability of AD mice, which may contribute to the resveratrol's antioxidation and
      antiapoptosis, and can modulate acetylcholinesterase. Resveratrol has no side
      effect of endometrial hyperplasia on AD mice.

PMID- 16951521
TI  - [Effects of rosiglitazone on endothelium-dependent vasodilation in patients with
      Type 2 diabetes].
AB  - OBJECTIVE: To investigate the effects of rosiglitazone on endothelium-dependent
      vasodilation in patients with Type 2 diabetes. METHODS: Eighty-three newly
      diagnosed patients with Type 2 diabetes were divided into metformin group
      (metformin 750 mg/d), therapeutic alliance group (rosiglitazone 4 mg/d and
      metformin 750 mg/d), and rosiglitazone group (rosiglitazone 4 mg/d), and 25
      normal subjects were as the control group. All patients were treated for 12
      weeks. The height, weight, blood pressure, fasting plasma glucose (FPG), fasting
      serum insulin (FINS), glycosylated hemoglobin (HbA1c), triglyceride (TG), total
      cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density
      lipoprotein cholesterol (HDL-C), and serum nitric oxide (NO) were measured before
      and after the therapy. The body mass index (BMI) and homeostasis model assessment
      insulin resistant index (HOMA-IR) were calculated. The flow-mediated dilatation
      (FMD) and endothelium independent dilatation (EID) were measured by high
      resolution ultrasound. RESULTS: The BMI, TG, TC, LDL-C, FPG, HBA1c, HOMA-IR were
      higher (P<0.01), but HDL-C, NO, FMD were lower (P<0.01) in all diabetic groups
      than those in the control group before the treatment. After the 12-week
      treatment, TG, FPG, HBA1c, HOMA-IR decreased significantly in all the diabetic
      groups (P<0.01); FINS decreased, but HDL-C, NO, FMD and EID increased (P<0.01) in
      therapeutic alliance group and rosiglitazone groups, while HDL-C, FINS, NO, FMD
      had no change in metformin group compared with those before the treatment.
      CONCLUSION: Endothelium-dependent vasodilation function is impaired in patients
      with Type 2 diabetes. The therapy with rosiglitazone can increase the serum NO
      level, and improve endothelium-dependent vasodilation,but metformin has no
      influence on the above-mentioned indexes.

PMID- 16951522
TI  - [Effects of high glucose on the cell proliferation, damage and cytokine in human
      peritoneal mesothelial cells].
AB  - OBJECTIVE: To determine the mechanism of peritoneal fibrosis of peritoneal
      mesothelial cells by high glucose. METHODS: The third passage human peritoneal
      mesothelial cells (HPMCs) from primary culture were divided into a control group
      (F(12)) and high glucose groups (F(12)+4% glucose) in different times (24, 48 h).
      The cell proliferation was assayed by the method of MTT
      (methylthiazoletetrazolium). The cell damage was measured by LDH (lactate
      dehydrogenase). The protein expression of fibronectin (FN), transforming growth
      factor-beta1(TGF-beta(1)) and connective tissue growth factor (CTGF) were
      detected by ELISA. The mRNA expression of FN, TGF-beta(1) and PAI-1 were detected
      by RT-PCR. RESULTS: High glucose suppressed the cell proliferation. The result of
      MTT showed that compared with the control group, the value of OD of high glucose
      groups at 24 or 48 h decreased significantly (P<0.01 or 0.01); The cell damage
      was enhanced in high glucose groups, at 24 or 48 h compared with the control
      group at the same time (all P<0.01). The protein expressions of TGF-beta(1), CTGF
      and FN in supernate fluid of cell culture were significantly enhanced when high
      glucose stimulated the HPMCs in the high glucose groups at 24 or 48 h compared
      with the control group at the same time (P<0.05 or 0.001). The expressions of FN,
      TGF-beta(1) and PAI-1 mRNA were upregulated in 24 h high glucose group compared
      with that of 24 h control group. CONCLUSION: High glucose can suppress the HPMC
      proliferation and damage HPMCs. Increase of TGF-beta(1), CTGF, FN and PAI-1 of
      HPMCs stimulated by high glucose can promote the synthesis and decreased
      degradation of extracellular matrix, which might be related with the mechanism of
      peritoneal fibrosis of peritoneal mesothelial cells by high glucose.

PMID- 16951523
TI  - [Application of continuous renal replacement therapy in the rescue of MODS
      patients].
AB  - OBJECTIVE: To investigate the effect of continuous renal replacement therapy
      (CRRT) on patients with emergency and serious diseases. METHODS: The patients
      were divided into 2 groups: Group A [71 patients with multiple organ dysfunction
      syndrome (MODS)] were treated by CRRT for 175 times. Group B (30 patients) were
      treated with common hematodialysis (HD). Blood urea nitrogen (BUN), serum
      creatinine (Scr), natrem (Na(+)), kalium (K(+)), chlorine (Clj), power of
      hydrogen (pH), bicarbonate (HCO3-), carbon dioxide partial pressure (PCO(2)), and
      oxygen pressure (PO(2)) were measured before and after the treatment. RESULTS:
      After the treatment, all patients' general state of health, water-electrolyte and
      acid base disorder were improved. The levels of BUN, Scr, K(+) (All P(s)<0.01),
      and Na(+) (P<0.05 in Group A, P<0.01 in Group B) were all lower and the levels of
      CO(2)CP (P<0.01 in Group A, P<0.05 in Group B) were higher than that before the
      pretherapy in both Group A and Group B. There was significant difference on the
      levels of BUN, Scr, K(+)(All P(s)<0.01), Cl(-) and CO(2)CP (All P(s)<0.05)
      between Group A and Group B, which indicated the therapeutic effect in Group A
      was better than that in Group B. Furthermore, the levels of pH, PO(2) and HCO(3)(
      ) were higher (P<0.01) and PCO(2) was lower (P<0.05) obviously than that before
      the CRRT in 30 patients with acute respiratory distress syndrome (ARDS) in Group
      A. Among the 9 patients with poisoning, 7 were alleviated completely and 2 died
      after the CRRT plus hemoperfusion (HP). The survival time of patients was
      lengthened in Group A. No blood or bleed aggravation occurred in patients with
      bleeding inclination or 48 h before the operation after using the method of
      heparin soaking the blood filter. CONCLUSION: CRRT has better curative effect on
      removing the toxin effectively, rapidly correcting the turbulence of water
      electrolyte and sour-alkali balance for patients compare with HD. At the same
      time, it can increase the level of PO(2) and reduce CO(2) retention, improve the
      lung function and brain edema, and increase the patient's survival rate. Using
      CRRT as early as possible is very important and it can improve the prognosis of
      the patients who had MODS or other dangers because the death rate of MODS
      patients is very high.

PMID- 16951524
TI  - [Analysis of 92 ectopic pregnancy patients after in vitro fertilization and
      embryo transfer].
AB  - OBJECTIVE: To investigate the occurrence of ectopic pregnancy among women who
      received in vitro fertilization and assess the influential factors. METHODS: The
      indications, methods of assisted conception and ectopic types were analyzed
      retrospectively after the patients received in vitro fertilization and embryo
      transfer (IVF-ET), intracytoplasmic sperm injection (ICSI), or freezing-thawing
      embryo transfer (FET). RESULTS: A total of 6007 embryo transfers were performed,
      and 2322 (38.7%) clinical pregnancies were obtained. Ninety-four (4.05%) of them
      were ectopic pregnancies; and 92 were tubal pregnancies. The occurrence rate was
      3.96%, which constituted 97.87% (92/94) of all ectopic pregnancies. There were 2
      cases of other parts: one in abdominal cavity and the other in cornual pregnancy
      with the occurrence rate of 0.86%, constituting 2.32% (2/94). Twenty heterotopic
      pregnancies occurred (0.86%), constituting 21.28% (20/94). Among all ectopic
      pregnancies, the assisted conception of 86 cases was tubal pathology and/or
      pelvic adherence (91.49%), and 24 patients had a history of ectopic pregnancy
      (25.53%). The differences of clinical pregnancy rates between IVF-ET, ICSI and
      FET were not significant (P>0.05). The ectopic rate of IVF-ET group was
      significantly higher than that of ICSI or FET group (P<0.05), respectively. The
      ectopic rate in FET group was also higher than that in ICSI group (P<0.05).
      CONCLUSION: The occurrence rate of ectopic pregnancy after IVF is higher than
      that of spontaneous pregnancy, and the main cause for ectopic pregnancy is the
      tubal pathological changes.

PMID- 16951525
TI  - [Surgical pattern of radical hysterectomy and pelvic lymph node dissection for
      patients with cervical cancer].
AB  - OBJECTIVE: To investigate the probability of improving radical surgery to resect
      uterus thoroughly and to decrease various complications after the surgery.
      METHODS: We compared the clinical effect of reformed radical hysterectomy for 79
      patients with the effect of tradition radical hysterectomy for 60 patients.
      Reformed surgery had the following features: We firstly resected the uterus and
      then dissected the pelvic lymph node. Urinary bladder gap and rectum gap were
      opened. After exposing the route of ureter, we excised the uterus artery at the
      point between the ureter and the uterus artery. Cardinal ligament and uterosacral
      ligament were cut off by electric knives. The pelvic lymph node was dissected
      with a titanium pinch. RESULTS: The average operation time and the time of
      keeping uterine pipe were shortened. Bleeding during the operation was reduced.
      No complication was observed. All patients were followed up for 11 to 20 months
      and no patient died. One patient recurred. CONCLUSION: Reformed surgery can
      resect the uterus, dissect the pelvic lymph node thoroughly, and reduce various
      complications. The reformed surgery can not only ensure the curative effect, but
      also benefit patient's recovery and life quality.

PMID- 16951526
TI  - [Therapeutic effects of intraarticular injection of ligustrazine on knee
      osteoarthritis].
AB  - OBJECTIVE: To evaluate the therapeutic effects of intraarticular injection of
      ligustrazine on knee osteoarthritis (OA). METHODS: Seventy-one cases of knee
      osteoarthritis (82 knees) were randomly divided into ligustrazine (LI) group and
      sodium hyaluronate (SH) group. The patients were intraarticularly injected
      ligustrazine or sodium hyaluronate once a week for 5 consecutive weeks, and were
      followed-up for 3 months. Lequesneos protocol for the evaluation of OA severity
      and activity was used. The therapeutic effects and changes of Lequesneos index
      were observed after the treatment. RESULTS: There was significant decrease in
      Lequesneos index in SH group after the treatment (P<0.01), but not in LI group
      (P>0.05). Three weeks later, there was significant decrease in Lequesneos index
      in both groups after the treatment (P<0.01), with no significant difference
      between SH and LI group (P>0.05). After the 5-week treatment, the efficacy rate
      of the LI group was 82.1%, and that of the SH group was 87.2%. No serious toxic
      or side effect was observed during the treatment and the follow-up. CONCLUSION:
      Intraarticular injection of ligustrazine has a therapeutic effect on knee OA. No
      adverse effect is observed, but it needs long time to take effect.

PMID- 16951527
TI  - [Clavicular hook plate in the treatment of dislocation of acromioclavicular joint
      and fracture of distal clavicle].
AB  - OBJECTIVE: To evaluate the curative effects of AO clavicular hook plate in the
      treatment of dislocation of acromioclavicular joint and fracture of distal
      clavicle. METHODS: We retrospectively analyzed the clinical data of 39 patients
      with acromioclavicular joint dislocation or distal clavicle fractures treated
      with clavicular hook plate: 16 suffered from dislocation of acromioclaviculr
      joint, 18 suffered from far end collarbone fractures, and 5 patients had both
      symptoms. RESULTS: The 39 patients were followed up for 12 months averagely. All
      patients got good reduction and fixation. The acromioclavicular joint
      subluxation, breakage, and loosening of the clavicular hook plate were not
      observed. The acromioclavicular joint recovered quickly. CONCLUSION: AO
      clavicular hook plate is a good choice for acromioclavicular joint dislocation
      and distal clavicular fracture.

PMID- 16951528
TI  - [Diagnosis and treatment of cauda equina syndrome secondary to lumbar disc
      herniation].
AB  - OBJECTIVE: To discuss the diagnosis and treatment of cauda equina syndrome.
      METHODS: Thirty-four cases of cauda equina syndrome from 1993 to 2005 were
      analysed retrospectively. Its clinical representation, pathology character and
      clinical outcome were observed. RESULTS: At follow-ups of 3 to 102 months after
      the treatment (averagely 43 months), the muscle strength and function of the
      constrictor began to resume to different degrees. Muscle strength resumed
      gradually one week after the operation, resumed faster 3 months after the
      operation, and resumed completely more one year later. Function of the
      constrictor began to resume 3 days after the operation, and resumed mostly six
      months or so after the operation. Sense resumed slowly. CONCLUSION: Clinical
      outcome of cauda equina syndrome is good. Resumption after the operation
      obviously correlates to the time of operation. One week after the operation, the
      kinetic function resumes best, function of the constrictor resumes well and the
      sense function of the saddle area resumes not very well.

PMID- 16951529
TI  - [Cause and treatment of dysuria post trans-urethral resection of prostate].
AB  - OBJECTIVE: To evaluate the cause and treatment of dysuria post trans-urethral
      resection of prostate (TURP). METHODS: The clinical data and the treatment of 22
      cases of dysuria post TURP were analyzed retrospectively. RESULTS: All cases
      including 3 cases of glandular and extraneous material residual, 5 cases of
      urethrostenosis, 7 cases of bladder neck contracture, and 7 cases of detrusor
      muscle weakness, were cured after the treatment. CONCLUSION: The main causes of
      dysuria post TURP were glandular residual, urethrostenosis, bladder neck
      contracture, and detrusor muscle weakness. Correct preoperative diagnosis and
      treatment during/post operation are the key to the prevention of dysuria post
      TURP.

PMID- 16951530
TI  - [Retroperitoneal laparoscopic enucleation of the renal hamartoma].
AB  - OBJECTIVE: To investigate the operative technique and the clinical value of
      retroperitoneal laparoscopic enucleation of the renal hamartoma. METHODS: Twenty
      five patients of renal hamartoma received retroperitoneal laparoscopic
      enucleation. The patients were placed in lateral decubitus position. All
      laparoscopic surgical procedures were performed retroperitoneally using 3 port
      sites. The tumor was exposed and resected along the edge, and the tumor clipped
      out with a lithotomy forceps. The renal hamartoma was confirmed through a
      pathological diagnosis during the operation. The resection surface was sutured
      with fibrin and absorbable hemostatic gauze. RESULTS: The operations were
      finished successfully in all patients. The diameter of tumors ranged from 1.8 cm
      x 2.0 cm to 4.5 cm x 4.9 cm. The operative time was 50 - 90 (mean=70) min. The
      blood loss was 30 - 80 (mean=55) mL. The hospital stay was 7 - 9 (mean=8) days.
      CONCLUSION: Retroperitoneal laparoscopic enucleation of the renal hamartoma is
      safe and effective, whose advantages include minimal invasive, less blood loss,
      short hospital stay, and rapid convalescence.

PMID- 16951531
TI  - [Surgical treatment for lumbar discogenic low back pain].
AB  - OBJECTIVE: To explore the curative effect of surgical treatment for lumbar
      discogenic low back pain. METHODS: Forty-two patients with lumbar discogenic low
      back pain were treated with disc excision and lumbar interbody fusion: 12 of them
      were treated with posterior lumbar interbody fusion (PLIF), 30 with afront lumbar
      interbody fusion (ALIF). The clinical results were evaluated by pre- and post
      operative visual analogue scale (VAS), and the fusion rates of the lumbosacral
      spine were evaluated by X-ray. RESULTS: The average follow-up period was 18
      months, ranging from 6 to 36 months. Low back pain basically disappeared in 11
      patients treated with PLIF, with mild back pain in one patient; VAS after the
      operation decreased significantly in comparison with that preoperatively
      (P<0.01). Low back pain basically disappeared in 28 patients treated with ALIF;
      VAS after the operation decreased significantly in comparison with that
      preoperatively (P<0.01). The fusion rate was 90% in patients treated with PLIF,
      and 93% in patients with ALIF. CONCLUSION: Disc excision and interbody fusion is
      effective in the treatment of lumbar discogenic low back pain, but the operation
      indications should be paid attention to.

PMID- 16951532
TI  - [Determination of rhodamine 123 in cell lysate by high-performance liquid
      chromatography with visible wavelength detection].
AB  - OBJECTIVE: To establish a high-performance liquid chromatography with visible
      wavelength detection method for rhodamine 123 in cell lysate. METHODS: The HPLC
      separation was performed on a Kromasil C(18) (5 microm, 4.6 mm x 250 mm) column,
      using water (15 mmol/L potassium acetate and 1.2 mmol/L tetrabutylammonium
      bromide) - acetonitrile (65:35) as the mobile phase. The wave length was 390 nm,
      the internal standard was rhodamine B. Protein in the sample was precipitated by
      trichloroacetic acid. RESULTS: The calibration curve was linear in the range of 3
      - 300 microg/L. The intra-day and inter-day RSDs were less than 5%. CONCLUSION:
      The method is accurate,sensitive, simple, and reliable for determining rhodamine
      123 in cell lysate.

PMID- 16951533
TI  - [A case of malignant hyperthermia in general anesthesia].

PMID- 16951534
TI  - [Two cases of tetralogy of Follot with pregnancy].

PMID- 16951535
TI  - X-ray irradiation altered chemosensitivity of a p53-null non-small cell lung
      cancer cell line.
AB  - Radiotherapy is an effective approach to treating many types of cancer. Recent
      progress in radiotherapy technology, such as intensity-modulated radiation
      therapy (IMRT) and three-dimensional (3D) radiotherapy, allow precise energy
      transfer to the tumor, which has improved local control rates. However, the
      emergence of tolerant cells during or after radiotherapy remains problematic. In
      the present study, we first established a cell population from H1299, the p53
      null non-small cell lung cancer cell line, by 10 Gy irradiation using 6 MV X
      rays. The radio- and chemosensitivity of this cell population (referred to as
      H1299-IR) was determined using colony formation analyses and MTS assays. Compared
      with the parental cell line, the radiosensitivity of H1299-IR was apparently the
      same. H1299 and H1299-IR were both more radio tolerant than the A549 cell line.
      However, H1299-IR became significantly more sensitive to cisplatin, an antitumor
      agent. After exposure to 25 mug/ml cisplatin for 2 h, parental cells steadily
      grew during the MTS assay, whereas the sensitivity of H1299-IR cells doubled both
      at 24 and 48 h. Microarray analysis of over 30,000 H1299-IR genes (Agilent
      Technology) revealed that 12 and 15 genes were up- (> 2.0) and down- (< 2.0)
      regulated, respectively. Rad51d (homologous recombination repair protein) gene
      was down-regulated 2.8-fold, whereas matrix metalloproteinase 1 (collagenase-1)
      gene was up-regulated 4.4-fold. These results indicated that some p53-null non
      small cell lung cancers could be successfully treated when X-ray radiotherapy was
      administered with subsequent or concurrent cisplatin chemotherapy.

PMID- 16951536
TI  - Relationships of age at menarche and menopause, and reproductive year with
      mortality from cardiovascular disease in Japanese postmenopausal women: the JACC
      study.
AB  - BACKGROUND: Early menopause is associated with increased risk of coronary heart
      disease in Caucasian women. However, this association has not been examined in
      Asian women. METHODS: We conducted a 10-year cohort study of 37,965 Japanese post
      menopausal women aged 40-79 years in the Japan Collaborative Cohort (JACC) Study.
      Causes of death were determined based on the International Classification of
      Disease. RESULTS: There were 487 mortality of stroke and 178 mortality of
      coronary heart disease. Late menarche or early menopause, or shorter duration of
      reproductive period was not associated with risk of mortality from coronary heart
      disease. However, compared with women with age at menarche < or =13 years, those
      with age at menarche > or =17 years tended to have increased risk of mortality
      from stroke: the multivariable hazard ratio was 1.32 (95% confidence interval
      [CI]: 0.93-1.87, p = 0.10). Compared with women with age at menopause of > or =49
      years, those with age at menopause of <49 years tended to have increased risk of
      coronary heart disease among women aged 40-64 years; the multivariable hazard
      ratio was 1.85 (95% CI: 0.92-3.73, p = 0.08). CONCLUSIONS: The possible
      association between early menopause and coronary heart disease among middle-aged
      women was consistent with the result of observational studies for Caucasian
      women, and can be explained by a protective effect of endogenous estrogen on the
      development of atherosclerosis.

PMID- 16951537
TI  - Smoking, alcohol drinking, green tea consumption and the risk of esophageal
      cancer in Japanese men.
AB  - BACKGROUND: Although smoking and alcohol drinking are established risk factors of
      esophageal cancer, their public health impact is unclear. Furthermore, the effect
      of green tea is controversial. METHODS: The present study was based on a pooled
      analysis of two prospective cohort studies. A self-administered questionnaire
      about health habits was distributed to 9,008 men in Cohort 1 and 17,715 men in
      Cohort 2, aged 40 years or older, with no previous history of cancer. We
      identified 38 and 40 patient cases with esophageal cancer among the subjects in
      Cohort 1 (9.0 years of follow-up) and Cohort 2 (7.6 years of follow-up),
      respectively. Cox proportional hazards regression was used to estimate hazard
      ratios (HRs) of the risk of esophageal cancer incidence. RESULTS: Cigarette
      smoking, alcohol drinking and green tea consumption were significantly associated
      with an increased risk of esophageal cancer. Compared with men who had never
      smoked, never drunk alcohol or green tea, the pooled multivariate HRs (95%
      confidence intervals) were 5.09 (1.80-14.40) (p for trend <0.0001), 2.73 (1.55
      4.81) (p for trend=0.0002), or 1.67 (0.89-3.16) (P for trend=0.04) for men who
      were currently smoking > or =20 cigarettes/day, drinking alcohol daily, or
      drinking > or =5 cups green tea/day, respectively. The population attributable
      fractions of esophageal cancer incidence that was attributable to smoking,
      alcohol drinking and green tea consumption were 72.0%, 48.6%, and 22.1%,
      respectively. CONCLUSIONS: Among the variables studied, smoking has the largest
      public health impact on esophageal cancer incidence in Japanese men, followed by
      alcohol drinking and green tea drinking.

PMID- 16951538
TI  - Impact of non-dietary nutrients intake on misclassification in the estimation of
      nutrient intake in epidemiologic study.
AB  - BACKGROUND: Few previous epidemiologic studies have evaluated the effects of non
      dietary nutrient intake, such as supplements, over the counter (OTC) drugs, and
      prescription drugs containing vitamins or minerals, in examining the relationship
      between dietary factors and health outcomes. METHODS: To examine the influence of
      the non-dietary intake of vitamins and calcium on the estimation of nutrient
      intake, we conducted a cross-sectional study with 1,168 community-dwelling
      Japanese subjects aged 70 years or older in 2002. The subjects were asked to
      bring their non-dietary nutrient sources to the examining site. The dietary and
      non-dietary intakes of vitamins B1, C, E and calcium were obtained and the
      subjects were grouped into quartiles according to their dietary intake and their
      dietary plus non-dietary intake. The degree of agreement between these two
      classifications was examined to estimate the degree of misclassification.
      RESULTS: Among the subjects who were classified into the highest intake category
      for vitamin E with dietary intake plus non-dietary nutrient intake, 34.2 % were
      misclassified into lower category with dietary intake alone. Similarly, intake of
      vitamin B(1), vitamin C and calcium were misclassified 28.8%, 18.8 %, 6.2 %,
      respectively. CONCLUSIONS: Our data suggest that estimation of vitamin intake
      from dietary sources alone would yield a maximum misclassification of one-third,
      which would lead to misleading conclusions being drawn from epidemiologic
      studies. In contrast, the degree of misclassification for calcium may be
      relatively small.

PMID- 16951539
TI  - Pravastatin use and the five-year incidence of cancer in coronary heart disease
      patients: from the prevention of coronary sclerosis study.
AB  - BACKGROUND: Although the short-term safety of statins is well established, their
      potential carcinogenicity in the long term is still being debated. The aim of
      this study was to investigate the association between statin-therapy and the
      incidence of cancer in coronary heart disease patients. METHODS: The subjects
      were 263 patients with coronary heart disease who were from Osaka prefecture and
      who were admitted to the Osaka Medical Center for Cancer and Cardiovascular
      Diseases between September 28, 1991 and March 31, 1995. The five-year cancer
      incidence among the subjects was checked using the database of the institution
      based cancer registry of the hospital as well as the population-based Osaka
      Cancer Registry. The Cox's proportional hazards ratios (HRs) of all cancer
      incidence and observed/expected (O/E) ratios by cancer site were calculated.
      RESULTS: Cancer incidence was observed in 17 patients during the follow-up
      period. Age (HR=1.16 per one year of age) and continuous smoking during the
      period (HR=5.82 compared to not smoking during the period) were significantly
      associated with cancer incidence using multivariable analysis. After being
      adjusted for sex, age, total serum cholesterol level and smoking habit, the HR of
      cancer incidence with pravastatin use was 0.78 (95% confidence interval: 0.18
      3.46). In the O/E analysis, significantly elevated risks were found for bladder
      cancer in all the subjects (HR=8.93), as well as in the pravastatin use patients
      (HR=13.76). CONCLUSIONS: Pravastatin use for 5 years did not indicate an increase
      in over all cancer risk.

PMID- 16951540
TI  - Arsenic in drinking water and peripheral nerve conduction velocity among
      residents of a chronically arsenic-affected area in Inner Mongolia.
AB  - BACKGROUND: It remains unclear whether chronic ingestion of arsenic in drinking
      water affects the peripheral nervous system. We examined the effects of arsenic
      exposure on nerve conduction velocity using electromyography. METHODS: A cross
      sectional study was conducted of a population living in an arsenic-affected
      village in Hetao Plain, Inner Mongolia, China. A total of 134 (93.7%) of 143
      inhabitants took part in the study, and 36 (76.6%) of 47 inhabitants in a low
      arsenic exposed village were recruited as a control group. Of the participants,
      109 inhabitants in the arsenic-affected village and 32 in the low-arsenic exposed
      village aged > or =18 years were used for the analyses. An expert physician
      performed skin examinations, and median nerve conduction velocity was examined by
      electromyography. Arsenic levels in tube-well water and urine were measured. A
      mean level of arsenic in tube-well water in the arsenic-affected village was
      158.3 microg/L, while that in the low-arsenic exposed village was 5.3 microg/L.
      RESULTS: No significant differences in the means of the motor nerve conduction
      velocity (MCV) and sensory nerve conduction velocity (SCV) were observed in
      relation to arsenic levels in tube wells, urine, and the duration of tube-well
      use. Further, no differences in mean MCV or SCV were found between the subjects
      with and without arsenic dermatosis, with mean SCV of 52.8 m/s (SD 6.3) in those
      without and 54.6 m/s (5.2) in subjects with arsenic dermatosis (p=0.206).
      CONCLUSION: These findings suggest that chronic arsenic poisoning from drinking
      water is unlikely to affect nerve conduction velocity, at least within the range
      of arsenic in drinking water examined in the present study.

PMID- 16951541
TI  - Reasons for permanent tooth extractions in Japan.
AB  - BACKGROUND: There has been no nationwide study in Japan on reasons for extraction
      of permanent teeth. This survey was aimed to determine the reasons for extraction
      of permanent teeth in Japan. METHODS: Five thousand, one hudred and thirty-one
      dentists were selected by systematic selection from the 2004 membership directory
      of the Japan Dental Association. The dentists selected were asked to record the
      reason for each extraction of permanent teeth during a period of one week from
      February 1 through 7, 2005. Reasons for tooth extraction were assigned to five
      groups: caries, fracture of teeth weakened by caries or endodontics, periodontal
      diseases, orthodontics, and other reasons. RESULTS: A total of 2,001 dentists
      (response rate of 39.1%) returned the questionnaires, and information on 9,115
      extracted teeth from 7,499 patients was obtained. The results showed that caries
      and its sequela (totally 43.3%, 32.7% and 10.6%, respectively) and periodontal
      disease (41.8%) were the main reasons for teeth extraction. Extraction due to
      caries or fracture was commonly observed in all age groups over 15 years of age,
      whereas periodontal disease was predominant in the groups over 45 years of age.
      CONCLUSIONS: Most of the permanent teeth were extracted due to caries and its
      sequela and periodontal disease. Prevention and care for dental caries for all
      age groups and periodontal disease for over middle age groups are required.

PMID- 16951542
TI  - Expression of amphiregulin during the pre- and post-implantation period in the
      mouse reproductive tract.
AB  - In mammals, embryo implantation is an essential step in reproduction.
      Implantation is a phenomenon that involves crosstalk between the blastocyst and
      the maternal endometrium. However, the molecular basis of the connections between
      the blastocyst and endometrium is not yet fully understood. Amphiregulin is a
      member of the epidermal growth factor family and is known to be expressed in the
      luminal epithelium of the mouse uterus on 3.5 days post coitum (dpc). Thus, to
      clarify the mechanism of amphiregulin at fetomaternal interface, we analyzed the
      expression pattern of amphiregulin mRNA in the oviducts and uteri of pregnant and
      psuedopregnant mice by means of real-time PCR. Amphiregulin expression in the
      pregnant uterus dramatically increased on 2.5 dpc, peaked on 3.5 dpc, and
      declined by 5.5 dpc. Furthermore, to analyze the effect of the presence of an
      embryo on amphiregulin expression, we determined the expression pattern of
      amphiregulin mRNA in the uterus after embryo transfer on 0.5 and 1.5 dpc. A
      previous study showed that the expression of amphiregulin mRNA depends on the
      concentration of progesterone. However, our present results indicate that
      amphiregulin mRNA is upregulated by the presence of fertilized eggs in the lumen
      of the oviduct on 0.5 dpc.

PMID- 16951543
TI  - Regulation of NFAT activation: a potential therapeutic target for
      immunosuppression.
AB  - The NFAT family of transcription factors plays pivotal roles in the development
      and function of the immune system. Their activation process is tightly regulated
      by calcium-dependent phosphatase calcineurin and has been a target of the
      immunosuppressive drugs cyclosporin A and FK-506. Although the clinical use of
      these drugs has dramatically increased the success of organ transplantation,
      their therapeutic use is limited by severe side effects. Recent studies for the
      calcineurin/NFAT signaling pathway have identified a number of cellular proteins
      that inhibit calcineurin function. Specific peptide sequences that interfere with
      the interaction between calcineurin and NFAT have also been characterized.
      Moreover, diverse approaches to identify small organic molecules that modulate
      NFAT function have been performed. This review focuses on the recent advances in
      our understanding of the inhibitory modulation of NFAT function, which may open
      up the additional avenues for immunosuppressive therapy.

PMID- 16951544
TI  - Inductin of neuron-derived orphan receptor-1 in the dentate gyrus of the
      hippocampal formation following transient global ischemia in the rat.
AB  - Neuron-derived orphan receptor (NOR-1) is a member of the thyroid/steroid
      receptor superfamily that was originally identified in forebrain neuronal cells
      undergoing apoptosis. In addition to apoptotic stimuli, activation of several
      signal transduction pathways including direct neuronal depolarization regulates
      the expression of NOR-1. In this study we tested whether the expression of NOR-1
      is changed following transient ischemic injury in the adult rat brain. NOR-1 mRNA
      increased rapidly in the dentate gyrus of the hippocampal formation and piriform
      cortex 3 h after transient global ischemia and returned to basal level at 6 h. On
      the other hand, oxygen-glucose deprivation of cultured cerebral cortical neurons
      did not alter the expression of NOR-1. These results suggest that expression of
      NOR-1 is differentially regulated in different brain regions in response to
      globally applied brain ischemia, but that hypoxia is not sufficient to induce its
      expression.

PMID- 16951545
TI  - Molecular and structural characterization of the domain 2 of hepatitis C virus
      non-structural protein 5A.
AB  - Hepatitis C virus (HCV) non-structural protein 5A protein (NS5A), which consists
      of three functional domains, is involved in regulating viral replication,
      interferon resistance, and apoptosis. Recently, the three-dimensional structure
      of the domain 1 was determined. However, currently the molecular basis for the
      domains 2 and 3 of HCV NS5A is yet to be defined. Toward this end, we expressed,
      purified the domain 2 of the NS5A (NS5A-D2), and then performed biochemical and
      structural studies. The purified domain 2 was active and was able to bind NS5B
      and PKR, biological partners of NS5A. The results from gel filtration, CD
      analysis, 1D 1H NMR and 2D 1H-15N heteronuclear single quantum correlation (HSQC)
      spectroscopy indicate that the domain 2 of NS5A appears to be flexible and
      disordered.

PMID- 16951546
TI  - Hydrogen peroxide induces apoptosis of BJAB cells due to formation of hydroxyl
      radicals via intracellular iron-mediated Fenton chemistry in glucose oxidase
      mediated oxidative stress.
AB  - The aim of this study was to determine if hydrogen peroxide (H2O2) generated by
      glucose oxidase (GO) induces apoptosis or necrosis of BJAB cells and which
      radical is the direct mediator of cell death. We found that GO produced H2O2
      continuously in low concentrations, similar to in vivo conditions, and decreased
      proliferation and cell viability in a dose-dependent manner. The GO-mediated
      cytotoxicity resulted from apoptosis, and was confirmed by monitoring the cells
      after H33342/Annexin V/propidium iodide staining. Decreases of mitochondrial
      membrane potential and intracellular glutathione level were found to be critical
      events in the H2O2-mediated apoptosis. Additional experiments revealed that H2O2
      exerted its apoptotic action through the formation of hydroxyl radicals via the
      Fenton rather than the Haber-Weiss reaction. Moreover, intracellular redox-active
      iron, but not copper, participated in the H2O2-mediated apoptosis.

PMID- 16951547
TI  - Munc18 plays an important role in the regulation of glutamate release during
      female puberty onset.
AB  - Munc18, a mammalian homolog of C. elegans Unc, is essential for neurotransmitter
      release. The aim of this study was to identify estrogen-dependent expression of
      Munc18-1 and its role in the regulation of glutamate release for puberty onset.
      Hypothalamic munc18-1 mRNA levels were significantly increased by estrogen
      treatment in ovariectomized, immature female rats. During pubertal development,
      the munc18-1 mRNA levels dramatically increased between the juvenile period and
      the anestrous phase of puberty. Intracerebroventricular administration of an
      antisense oligodeoxynucleotide against munc18-1 mRNA significantly decreased
      glutamate release and delayed the day of puberty onset. These results suggest
      that Munc18-1, expressed in an estrogen-dependent manner, plays an important role
      in the onset of female puberty via the regulation of glutamate release.

PMID- 16951548
TI  - Proteomic analysis of the hydrophobic fraction of mesenchymal stem cells derived
      from human umbilical cord blood.
AB  - Mesenchymal stem cells (MSCs) are promising candidates for cell therapy and
      tissue engineering, but their application has been impeded by lack of knowledge
      of their core biological properties. In order to identify MSC-specific proteins,
      the hydrophobic protein fraction was individually prepared from two different
      umbilical cord blood (UCB)-derived MSC populations; these were then subjected to
      two-dimensional (2D) gel electrophoresis and peptide mass fingerprinting matrix
      assisted laser desorption/ionization (MALDI)-time of flight (TOF)-mass
      spectrometry (MS). Although the 2D gel patterns differed somewhat between the two
      samples, computer-assisted image analysis identified shared protein spots. 35
      spots were reliably identified corresponding to 32 different proteins, many of
      which were chaperones. Based on their primary sub-cellular locations the proteins
      could be grouped into 6 categories: extracellular, cell surface, endoplasmic
      reticular, mitochondrial, cytoplasmic and cytoskeletal proteins. This map of the
      water-insoluble proteome may provide valuable insights into the biology of the
      cell surface and other compartments of human MSCs.

PMID- 16951549
TI  - Activation of p38 MAPK is involved in endothelin-1-stimulated COX-2 expression in
      cultured Feline esophageal smooth muscle cells.
AB  - We investigated the possible role of p38 MAPK and ETB receptors in ET-1 induction
      of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in cultured feline
      esophageal smooth muscle cells (ESMC). Confluent layers of ESMC were stimulated
      with 10 nM ET-1 and expression of COX-1 and COX-2, involvement of receptors, and
      activation of p38 MAPK, were examined by Western blot analysis. Levels of PGE2
      induced by ET-1 were measured by Elisa. Using ETA and ETB antagonists (BQ-123 and
      BQ-788, respectively), the contribution of the ET receptors to COX-1 and COX-2
      expression induced by ET-1 was determined. Western blot analysis revealed that
      treatment of ESMC with ET-1 resulted in transient expression of COX-2 and
      activation of p38 MAPK. Activation of p38 MAPK was maximal after 1 h. SB202190, a
      p38 MAPK inhibitor, reduced expression of COX-2, but not COX-1. ET-1-induced
      release of PGE2 was also blocked by SB202190. COX-2 expression was upregulated
      only via the ETB receptor, and COX-1 expression was not affected by either
      antagonist. Taken together, our data suggest that ET-1 causes p38 MAPK-dependent
      expression of COX-2 by interacting with ETB receptors on ESMC.

PMID- 16951550
TI  - Haloperidol induces calcium ion influx via L-type calcium channels in hippocampal
      HN33 cells and renders the neurons more susceptible to oxidative stress.
AB  - Haloperidol is a classical neuroleptic drug that is still in clinical use and can
      lead to abnormal motor activity following repeated administration. However, there
      is little knowledge of how it triggers neuronal impairment. In this study, we
      report that it induced calcium ion influx via L-type calcium channels and that
      the elevation of calcium ions induced by haloperidol appeared to render
      hippocampal cells more susceptible to oxidative stress. Indeed, the level of
      cytotoxic reactive oxygen species (ROS) and the expression of pro-apoptotic Bax
      increased in response to oxidative stress in haloperidol-treated cells, and these
      effects were inhibited by verapamil, a specific L-type calcium channel blocker,
      but not by the T-type calcium channel blocker, mibefradil. These findings
      indicate that haloperidol induces calcium ion influx via L-type calcium channels
      and that this calcium influx influences neuronal fate.

PMID- 16951551
TI  - CaWRKY2, a chili pepper transcription factor, is rapidly induced by incompatible
      plant pathogens.
AB  - WRKY family proteins are a class of plant-specific transcription factors involved
      in stress response signaling pathways. In this study a gene encoding a putative
      WRKY protein was isolated from a pepper EST database
      (http://genepool.kribb.re.kr). The cDNA, named Capsicum annuum WRKY2 (CaWRKY2),
      encodes a putative polypeptide of 548 amino acids, containing two WRKY domains
      with zinc finger motifs and two potential nuclear localization signals. Northern
      blot analyses showed that CaWRKY2 mRNA was preferentially induced during
      incompatible interactions of pepper plants with PMMoV, Pseudomonas syringae pv.
      syringae 61, and Xanthomonas axonopodis pv. vesicatoria race 3. Furthermore,
      CaWRKY2 transcripts were strongly induced by wounding and ethephon treatment,
      whereas only moderate expression was detected following treatment with salicylic
      acid and jasmonic acid. CaWRKY2 was translocated to the nucleus when a CaWRKY2
      smGFP fusion construct was expressed in onion epidermal cells. CaWRKY2 also had
      transcriptional activation activity in yeast. Taken together our data suggest
      that CaWRKY2 is a pathogen-inducible transcription factor that may have a role in
      early defense responses to biotic and abiotic stresses.

PMID- 16951552
TI  - Involvement of the phospholipase C beta1 pathway in desensitization of the
      carbachol-activated nonselective cationic current in murine gastric myocytes.
AB  - In murine gastrointestinal myocytes muscarinic stimulation activates nonselective
      cation channels via a G-protein and Ca2+-dependent pathway. We recorded inward
      cationic currents following application of carbachol (ICCh) to murine gastric
      myocytes held at -60 mV, using the whole-cell patch-clamp method. The properties
      of the inward cationic currents were similar to those of the nonselective cation
      channels activated by muscarinic stimulation in other gastrointestinal smooth
      muscle cells. CCh-induced ICCh and spontaneous decay of ICCh (desensitization of
      ICCh) occurred. Unlike the situation in guinea pig gastric myocytes,
      desensitization was not affected by varying [EGTA]i. Pretreatment with the PLC
      inhibitor (U73122) blocked the activation of ICCh, and desensitization of ICCh
      was attenuated in PLC beta1 knock-out mice. These results suggest that the
      desensitization of ICCh in murine gastric myocytes is not due to a pathway
      dependent on intracellular Ca2+ but to the PLC beta1 pathway.

PMID- 16951553
TI  - Monoclonal antibody to CD9 inhibits platelet-induced human endothelial cell
      proliferation.
AB  - Platelets are anucleate cytoplasmic fragments derived from bone marrow
      megakaryocytes, and endothelial cells constitute the barrier between bloodstream
      and adjacent tissues. Although platelets are thought to regulate the biological
      functions of endothelial cells, the molecular mechanisms involved are poorly
      understood. With human umbilical vein endothelial cells and freshly isolated
      platelets, we established an in vitro model of platelet-induced endothelial cell
      proliferation. Platelets stimulated endothelial cell proliferation in a dose
      dependent manner and transwell experiments with semi-permeable membranes
      suggested that direct cell-to-cell contacts were required. We developed mAbs
      against platelets and selected a mAb that blocks their proliferative effect. We
      purified the antigen by immunoprecipitation and identified it by Q-TOF MS
      analysis as the tetraspanin CD9. Since both platelets and endothelial cells
      expressed CD9 strongly on their surfaces we carried out a pre-treatment
      experiment that showed that CD9 molecules on the endothelial cells participate in
      the mitogenic effect of the platelets. The inhibitory effect of our mAb was
      comparable to that of a well-known functional anti-CD9 mAb. These results suggest
      that the tetraspanin CD9 plays an important role in endothelial regeneration.

PMID- 16951554
TI  - Molecular phylogeny of the subfamily Tephritinae (Diptera: Tephritidae) based on
      mitochondrial 16S rDNA sequences.
AB  - The phylogeny of the subfamily Tephritinae (Diptera: Tephritidae) was
      reconstructed from mitochondrial 16S ribosomal RNA gene sequences using 53
      species representing 11 currently recognized tribes of the Tephritinae and 10
      outgroup species. The minimum evolution and Bayesian trees suggested the
      following phylogenetic relationships: (1) monophyly of the Tephritinae was
      strongly supported; (2) a sister group relationship between the Tephritinae and
      Plioreocepta was supported by the Bayesian tree; (3) the tribes Tephrellini,
      Myopitini, and Terelliini (excluding Neaspilota) were supported as monophyletic
      groups; (4) the non-monophyletic nature of the tribes Dithrycini, Eutretini,
      Noeetini, Tephritini, Cecidocharini, and Xyphosiini; and (5) recognition of 10
      putative tribal groups, most of which were supported strongly by the statistical
      tests of the interior branches. Our results, therefore, convincingly suggest that
      an extensive rearrangement of the tribal classification of the Tephritinae is
      necessary. Since our sampling of taxa heavily relied on the current accepted
      classification, some lineages identified by the present study were severely under
      sampled and other possible major lineages of the Tephritinae were probably not
      even represented in our dataset. We believe that our results provide baseline
      information for a more rigorous sampling of additional taxa representing all
      possible major lineages of the subfamily, which is essential for a comprehensive
      revision of the tephritine tribal classification.

PMID- 16951555
TI  - Molecular cloning of a pepper gene that is homologous to SELF-PRUNING.
AB  - "Determinate" and "indeterminate" inflorescences in plants are controlled by a
      single recessive gene, for example, SELF-PRUNING (SP) in Solanum lycopersicum,
      TERMINAL FLOWER1 in Arabidopsis, CENTRORADI-ALIS in Antirrhinum, and
      CENTRORADIALIS-like gene in tobacco. Pepper (Capsicum annuum L.) is an
      indeterminate species in which shoots grow indefinitely. In this study, we cloned
      and characterized the pepper SP-like gene (CaSP). RT-PCR revealed that the CaSP
      transcript accumulates to higher levels in floral buds than in other organs.
      Comparison of genomic DNA and cDNA sequences from indeterminate and determinate
      pepper plants revealed the insertion of a single base in the first exon of CaSP
      in the determinate pepper plants. CaSP is annotated in linkage group 8
      (chromosome 6) of the SNU2 pepper genetic map and showed similar synteny to SP in
      tomato. Transgenic tobacco plants overexpressing CaSP displayed late-flowering
      phenotypes similar to the phenotypes caused by overexpression of CaSP orthologs
      in other plants. Collectively, these results suggest that pepper CaSP is an
      ortholog of SP in tomato.

PMID- 16951556
TI  - Phosphate number and acyl chain length determine the subcellular location and
      lateral mobility of phosphoinositides.
AB  - Phosphoinositides are critical regulators of ion channel and transporter
      activity. There are multiple isomers of biologically active phosphoinositides in
      the plasma membrane and the different lipid species are non-randomly distributed.
      However, the mechanism by which cells impose selectivity and directionality on
      lipid movements and so generate a non-random lipid distribution remains unclear.
      In the present study we investigated which structural elements of
      phosphoinositides are responsible for their subcellular location and movement. We
      incubated phosphatidylinositol (PI), phosphatidylinositol 4-monophosphate
      (PI(4)P) and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) with short or long
      acyl chains in CHO and HEK cells. We show that phosphate number and acyl chain
      length determine cellular location and translocation movement. In CHO cells,
      PI(4,5)P2 with a long acyl chain was released into the cytosol easily because of
      a low partition coefficient whereas long chain PI was released more slowly
      because of a high partition coefficient. In HEK cells, the cellular location and
      translocation movement of PI were similar to those of PI in CHO cells, whereas
      those of PI(4,5)P2 were different; some mechanism restricted the translocation
      movement of PI(4,5)P2, and this is in good agreement with the extremely low
      lateral diffusion of PI(4,5)P2. In contrast to the dependence on the number of
      phosphates of the phospholipid head group of long acyl chain analogs, short acyl
      chain phospholipids easily undergo translocation movement regardless of cell type
      and number of phosphates in the lipid headgroup.

PMID- 16951557
TI  - DA-9601, Artemisia asiatica herbal extract, ameliorates airway inflammation of
      allergic asthma in mice.
AB  - We previously reported that DA-9601, ethanol herbal extract of Artemisia
      asiatica, inhibited histamine and leukotriene releases in guinea pig lung mast
      cells activated with specific antigen/antibody reaction. This study aimed to
      evaluate the inhibitory effect of DA-9601 on the OVA-induced airway inflammation
      in allergic asthma mouse model. BALB/c mice were sensitized and challenged with
      OVA. DA-9601 was administered orally 1 h before every local OVA-challenge. OVA
      specific serum IgE was measured by ELISA, recruitment of inflammatory cells in
      BAL fluids and lung tissues by Diff-Quik and H&E staining, respectively, the
      expressions of CD40, CD40L and VCAM-1 by immunohistochemistry, goblet cell
      hyperplasia by PAS staining, activities of MMPs by gelatin zymography,
      expressions of mRNA and proteins of cytokines by RT-PCR and ELISA, activities of
      MAP kinases by western blot, and activity of NF-KappaB by EMSA. DA-9601 reduced
      IgE level, recruitment of inflammatory cells into the BAL fluid and lung tissues,
      expressions of CD40, CD40L and VCAM-1 molecules, goblet cell hyperplasia, MMPs
      activity, expressions of mRNA and productions of various cytokines, activities of
      MAP kinases and NK-KappaB increased from OVA-challenged mice. These data suggest
      that DA-9601 may be developed as a clinical therapeutic agent in allergic
      diseases due to suppressing the airway allergic inflammation via regulation of
      various cellular molecules expressed by MAP kinases/NF-KappaB pathway.

PMID- 16951558
TI  - Effects of heterologous expression of thioredoxin reductase on the level of
      reactive oxygen species in COS-7 cells.
AB  - Thioredoxin reductase (TrxR), a component of the redox control system involving
      thioredoxin (Trx), is implicated in defense against oxidative stress, control of
      cell growth and proliferation, and regulation of apoptosis. In the present study
      a stable transfectant was made by introducing the vector pcDNA3.0 harboring the
      fission yeast TrxR gene into COS-7 African green monkey kidney fibroblast cells.
      The exogenous TrxR gene led to an increase in TrxR activity of up to 3.2-fold but
      did not affect glutathione (GSH) content, or glutaredoxin and caspase-3
      activities. Levels of reactive oxygen species (ROS), but not those of nitric
      oxide (NO), were reduced. Conversely, 1-chloro-2,4-dinitrobezene (CDNB), an
      irreversible inhibitor of mammalian TrxR, enhanced ROS levels in the COS-7 cells.
      After treatment with hydrogen peroxide, the level of intracellular ROS was lower
      in the transfectants than in the vector control cells. These results confirm that
      TrxR is a crucial determinant of the level of cellular ROS during oxidative
      stress as well as in the normal state.

PMID- 16951559
TI  - New protein extraction/solubilization protocol for gel-based proteomics of rat
      (female) whole brain and brain regions.
AB  - The rat is an accepted model for studying human psychiatric/neurological
      disorders. We provide a protocol for total soluble protein extraction using
      trichloroacetic acid/acetone (TCA/A) from rat (female) whole brain, 10 brain
      regions and the pituitary gland, and show that two-dimensional gel
      electrophoresis (2-DGE) using pre-cast immobilized pH (4-7) gradient (IPG) strip
      gels (13 cm) in the first dimension yields clean silver nitrate stained protein
      profiles. Though TCA/A precipitation may not be "ideal", the important choice
      here is the selection of an appropriate lysis buffer (LB) for solubilizing
      precipitated proteins. Our results reveal enrichment of protein spots by use of
      individual brain regions rather than whole brain, as well as the presence of
      differentially expressed spots in their proteomes. Thus individual brain regions
      provide improved protein coverage and are better suited for differential protein
      detection. Moreover, using a phosphoprotein-specific dye, in-gel detection of
      phosphoproteins was demonstrated. Representative high-resolution silver nitrate
      stained proteome profiles of rat whole brain total soluble protein are presented.
      Shortcomings apart (failure to separate membrane proteins), gel-based proteomics
      remains a viable option, and 2-DGE is the method of choice for generating high
      resolution proteome maps of rat brain and brain regions.

PMID- 16951560
TI  - A Timeless debate: resolving TIM's noncircadian roles with possible clock
      function.
AB  - Mammalian TIMELESS (TIM) was identified due to its sequence similarity to
      Drosophila TIM, an essential circadian clock protein in flies. Published
      literature is inconsistent regarding the rhythmic expression of mammalian Tim,
      the interaction of the TIM protein with other clock proteins and its role in
      regulating clock gene transcription. Comprehensive sequence analysis not only
      demonstrates that mammalian TIM is more similar to a second, TIM-like sequence in
      Drosophila (TIMEOUT), but is also a member of an evolutionarily conserved family
      of TIM orthologs that is distinct from the circadian-specific TIM proteins found
      in insects. The vital cellular function of these widely conserved TIM orthologs
      makes it difficult to determine the specific role of mammalian TIM in the
      circadian clock mechanism.

PMID- 16951561
TI  - Acid-sensing ion channel-1b in the stereocilia of mammalian cochlear hair cells.
AB  - We investigated whether amiloride-blockable proton-gated cation channels ASIC1a
      (acid-sensing ion channel-1a) and ASIC1b are expressed in the stereocilia of
      mouse cochlear hair cells. In-situ hybridization studies showed that ASIC1b
      transcripts, but not ASIC1a transcripts, were expressed in the inner and outer
      hair cells. Fluorescent immunohistochemical and immunogold electron microscopic
      analyses revealed that the ASIC1b channels were located at the insertions of the
      stereocilia into the hair cells. Our findings provide a novel molecular key to
      the understanding of cochlear physiology and pathophysiology.

PMID- 16951562
TI  - Neoculin, a taste-modifying protein, is recognized by human sweet taste receptor.
AB  - Neoculin, a sweet protein occurring in Curculigo latifolia, is unique in that it
      also has taste-modifying activity capable of converting sourness to sweetness.
      Calcium imaging analysis with HEK cells expressing the human sweet taste
      receptor, hT1R2/T1R3 demonstrated that the intracellular calcium concentration
      increased following the addition of 20 microM neoculin. The use of lactisole, a
      blocker of hT1R3, inhibited the intracellular calcium concentration increase
      almost completely. In sensory tests, when acetate buffers with different pH
      values were placed on the tongue after tasting neoculin, a higher intensity of
      sweetness was detected at lower pH. The sweetness was also suppressed with the
      addition of lactisole. These results suggest that both the sweetness and the
      taste-modifying activity are mediated via the human sweet taste receptor.

PMID- 16951563
TI  - Scarring impedes regeneration at sites of peripheral nerve repair.
AB  - We have investigated the effect of scarring at a site of peripheral nerve repair
      by comparing regeneration of the sciatic nerve in normal mice and two transgenic
      strains with an increased or decreased propensity for scarring. The outcome was
      assessed by quantifying collagen at the repair site, recording compound action
      potentials and counting myelinated nerve fibres on each side of the repair. We
      found that higher levels of collagen scar formation were associated with smaller
      compound action potentials, slower conduction velocities and a reduction in fibre
      numbers across the repair site. We conclude that scarring impedes regeneration at
      sites of nerve repair and suggest that this could be amenable to therapeutic
      manipulation.

PMID- 16951564
TI  - White matter abnormalities in dystonia normalize after botulinum toxin treatment.
AB  - The pathophysiology of dystonia is still poorly understood. We used diffusion
      tensor imaging to screen for white matter abnormalities in regions between the
      basal ganglia and the thalamus in cervical and hand dystonia patients. All
      patients exhibited an abnormal hemispheric asymmetry in a focal region between
      the pallidum and the thalamus. This asymmetry was absent 4 weeks after the same
      patients were treated with intramuscular botulinum toxin injections. These
      findings represent a new systems-level abnormality in dystonia, which may lead to
      new insights about the pathophysiology of movement disorders. More generally,
      these findings demonstrate central nervous system changes following peripheral
      reductions in muscle activity. This raises the possibility that we have observed
      activity-dependent white matter plasticity in the adult human brain.

PMID- 16951565
TI  - Agonist of proteinase-activated receptor 2 increases painful behavior produced by
      alpha, beta-methylene adenosine 5'-triphosphate.
AB  - Proteinase-activated receptor (PAR) 2 is expressed in a subset of primary
      afferent neurons and is involved in inflammatory nociception. The P2X3 ion
      channel is localized on nociceptors of sensory neurons. Using
      immunohistochemistry, we showed that many P2X3s are co-expressed with the PAR2 in
      rat dorsal root ganglia neurons. Nocifensive behavior induced by alphabeta
      methylene adenosine 5'-triphosphate (ATP) injection to the hind paw was
      significantly augmented after the application of PAR2 agonists. Fos expression
      induced by the alphabeta-methylene ATP injection in dorsal horn neurons was also
      increased after the pre-application of PAR2 agonists. These findings indicate
      that PAR2 agonists may potentiate the sensitivity of P2X3 ion channel to noxious
      stimuli, and the interaction between PAR2 and P2X3 may be an important mechanism
      underlying inflammatory pain.

PMID- 16951566
TI  - Muller glia induce retinal progenitor cells to differentiate into retinal
      ganglion cells.
AB  - Retinal progenitor cells could differentiate into various retinal cells that made
      cell-replacement therapy possible. Here, we investigated the role of cellular
      microenvironment on their regulation and differentiation and found that the
      percentage of proliferating cells and the percentage of retinal ganglion cells
      produced from them increased, when retinal progenitor cells were cocultured with
      Muller glia. Muller glia conditioned medium had the similar results. It is
      speculated that rather than traditional supportive roles, Muller glia may have an
      active regulatory role inducing retinal progenitor cells to proliferate and
      differentiate into ganglion cells by secreting some diffusible and membrane
      associated factors. Identification of Muller glia-derived factors will be made to
      elucidate the molecular mechanisms of neurogenesis.

PMID- 16951567
TI  - Magnetic targeting of bone marrow stromal cells into spinal cord: through
      cerebrospinal fluid.
AB  - We established a new magnetic targeting system in which bone marrow stromal cells
      migrate through the cerebrospinal fluid to the desired site in the spinal cord in
      rats. Subarachnoid injection has been reported as a minimally invasive method of
      transplantation of bone marrow stromal cells for spinal cord injury. It may be,
      however, less effective than direct injection into the spinal cord in terms of
      cell delivery. After implantation of a magnet, subarachnoid injection of bone
      marrow stromal cells labeled with magnetic beads was performed. Greater numbers
      of bone marrow stromal cells aggregated on the surface of the spinal cord owing
      to the magnetic force. This targeting system may be a useful tool in minimally
      invasive transplantation of bone marrow stromal cells for the treatment of spinal
      cord injury.

PMID- 16951568
TI  - Increasing cortical activity in auditory areas through neurofeedback functional
      magnetic resonance imaging.
AB  - We report a functional magnetic resonance imaging method to deliver task-specific
      brain activities as biofeedback signals to guide individuals to increase cortical
      activity in auditory areas during sound stimulation. A total of 11 study
      participants underwent multiple functional magnetic resonance imaging scan
      sessions, while the changes in the activated cortical volume within the primary
      and secondary auditory areas were fed back to them between scan sessions. On the
      basis of the feedback information, participants attempted to increase the number
      of significant voxels during the subsequent trial sessions by adjusting their
      level of attention to the auditory stimuli. Results showed that the group of
      individuals who received the feedback were able to increase the activation volume
      and blood oxygenation level-dependent signal to a greater degree than the control
      group.

PMID- 16951569
TI  - Diffusion-tensor magnetic resonance imaging in children with language impairment.
AB  - We evaluated the integrity of the white matter tract using diffusion-tensor
      magnetic resonance imaging in children with language impairments who exhibited a
      structurally normal brain on conventional magnetic resonance imaging, and
      compared it with age-matched normal children. After generating fractional
      anisotropy and color-coded vector maps, fractional anisotropy values of the major
      white matter tracts were measured in six locations and compared between the two
      groups. Compared with the normal control group, the fractional anisotropy values
      of children with language impairments showed a statistically significant
      reduction in the genu of the corpus callosum, which is rarely revealed on
      conventional magnetic resonance images. Our results suggest that delayed
      maturation of the white matter plays a partial role in the pathophysiological
      mechanisms of language impairments.

PMID- 16951570
TI  - Source analysis of epileptic discharges using multiple signal classification
      analysis.
AB  - Multiple signal classification is an alternative to the traditional dipole
      fitting source analysis methods. Our aim was to assess the clinical usefulness of
      this algorithm and to compare the localization of the epileptiform
      electroencephalography discharges with the regions of altered cerebral blood flow
      in 10 patients with complex partial seizures undergoing preoperative
      investigation. We performed multiple signal classification analysis of ictal and
      interictal discharges, and registered single-photon emission computed tomography.
      Localization of the ictal, but not the interictal discharges, as determined by
      multiple signal classification analysis was consistent with the regions showing
      perfusion changes on the single-photon emission computed tomography. Multiple
      signal classification analysis is a promising tool in localizing foci in patients
      with complex partial seizures and may contribute to the preoperative evaluation.

PMID- 16951571
TI  - A voxel-based morphometry study of gray matter in parents of children with
      autism.
AB  - Previous structural imaging studies of autistic individuals have identified gray
      matter abnormalities. It remains unclear, however, which abnormalities contribute
      to the etiology of autism and, among these abnormalities, which reflect genetic
      factors. Using voxel-based morphometry, we compared regional gray matter volume
      in 23 parents of autistic children to an age and sex-matched control sample. We
      identified relative local gray matter volume increases and decreases in the
      parent group that are consistent with previous research with autistic
      individuals. Further, differences were identified in regions that are
      functionally associated with social-cognitive and motor processes that are
      impaired in autism. This investigation constitutes the first whole-brain study of
      regional brain volume in the parents of autistic children, and suggests that a
      number of structural changes observed in autism may be familial.

PMID- 16951572
TI  - Identification of lexical-phonological networks in the superior temporal sulcus
      using functional magnetic resonance imaging.
AB  - General agreement exists that dorsal aspects of the temporal lobe support the
      perception of speech but there is less agreement regarding the mapping between
      levels of speech processing and neural regions within the dorsal temporal lobe.
      The present experiment sought to identify temporal lobe regions that support one
      such level, namely, lexical-phonological representation/processing. To do this,
      we manipulated phonological neighborhood density, a variable that affects
      processing within lexical-phonological networks. In a functional magnetic
      resonance imaging experiment, 10 participants listened to blocks of either high
      density or low-density words. High-density words produced significantly more
      activation in the posterior half of the superior temporal sulcus bilaterally,
      suggesting that these regions are involved in lexical-phonological processing
      networks.

PMID- 16951573
TI  - Differential brain-derived neurotrophic factor and transforming growth factor
      beta expression in the rat cochlea following deafness.
AB  - Brain derived neurotrophic factor (BDNF) and transforming growth factor-beta
      (TGFbeta) subtypes have demonstrated their importance in cochlear functions. The
      aim of this study was to determine gene and protein expression patterns of BDNF,
      TGFbeta1/2 and their main receptors trkB and TGFbetaR1/R2 in the auditory nerve
      and inferior colliculus of normal hearing and deafened rats by reverse
      transcriptase polymerase chain reaction and immunohistochemistry. Deafening was
      performed by cochlear injection of neomycin (10%). Significant gene expression
      changes were not found in the inferior colliculus after deafness; however, in the
      auditory nerve, BDNF, TGFbeta1 and TGFbetaR1 mRNA in particular were upregulated.
      Additionally, BDNF protein and the cytokines were found to be expressed in the
      auditory nerve after hair cell loss. These data indicate the importance of BDNF
      and TGFbeta1 as endogenous survival factors.

PMID- 16951574
TI  - Termination profiles of insect chemosensory afferents in the antennal lobe are
      dependent on their origin on the flagellum.
AB  - In cockroach antennae, sensory afferents from sensilla on the anterodorsal
      surface of the flagellum form the anterior antennal nerve, while afferents from
      the posteroventral surface form the posterior nerve. Anterograde staining was
      used to investigate afferent termination profiles in the glomeruli of the
      antennal lobe. The densities of terminal arborizations from the two nerves
      differed between glomeruli, with groupings of similar glomeruli evident.
      Individual glomeruli showed heterogeneous distribution of afferent terminals,
      with posterior nerve afferent terminals occurring near the nerve/glomeruli
      interface, and anterior nerve afferent terminals occurring on the opposite side.
      This study demonstrates, for the first time, a correlation between the
      distribution of primary afferent terminals in the individual glomeruli, and their
      origin on the surface of the flagellum.

PMID- 16951575
TI  - Neuromodulatory role of 5-hydroxytryptamine type 1A receptors on the excitability
      of Renshaw cells in the rat spinal cord.
AB  - Serotonin modulates neurotransmission at synapses between various spinal neurons
      and, thus, may either facilitate or depress the information processed in the
      circuits and ultimately modulate the final motor output. A possible
      neuromodulatory role of 5-hydroxytryptamine type 1A (5-HT1A) receptors on the
      excitability of lumbar spinal Renshaw cells was explored in anesthetized rats
      spinalized at T4 level. Intravenous administration of the specific 5-HT1A agonist
      (2R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT) (0.1
      mg/kg) decreased the Renshaw cell burst response by 20-45%. This effect was
      completely antagonized by the specific 5-HT1A antagonist (S)-N-tert-butyl-3-(4-(2
      methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide dihydrochloride [(S)-WAY
      100135] (0.1 mg/kg, intravenous), although this drug per se had no effect on the
      Renshaw cell burst response. These results suggest that 8-OH-DPAT-induced
      decrease in Renshaw cell burst firing was mediated by 5-HT1A receptors located
      either presynaptically or postsynaptically.

PMID- 16951576
TI  - Perineural clonidine reduces p38 mitogen-activated protein kinase activation in
      sensory neurons.
AB  - Perineural injection of clonidine at the site of nerve injury reduces
      hypersensitivity while simultaneously reducing leukocyte number and cytokine
      expression and hyperexcitability in sensory neurons. The activation of p38
      mitogen-activated protein kinase in sensory neurons contributes to the
      development and maintenance of inflammatory and neuropathic pain. Here, we tested
      whether perineural clonidine affected activation of p38 mitogen-activated protein
      kinase following partial sciatic nerve ligation. Perineural clonidine
      significantly increased withdrawal threshold and concomitantly reduced
      phosphorylation of p38 mitogen-activated protein kinase in sensory neurons
      ipsilateral to injury. Clonidine's effects were blocked by the alpha2
      adrenoceptor antagonist, BRL44408. These data suggest that activation of alpha2
      adrenoceptors at the site of nerve injury, probably by immune modulation, reduces
      intracellular signaling in primary afferents that leads to hypersensitivity.

PMID- 16951577
TI  - Dextromethorphan protects male but not female mice with brain ischemia.
AB  - The non-competitive N-methyl-D-aspartate receptor antagonist dextromethorphan is
      protective against some types of brain injury. Unilateral carotid ligation in
      postnatal day 12 CD1 mice produces ischemic brain injury. To evaluate the
      neuroprotective potential of dextromethorphan against ischemic injury in the
      immature brain, seven litters of postnatal day 12 CD1 mice received either
      dextromethorphan or vehicle after a unilateral carotid ligation. Only the male
      pups were protected, and brain injury was unchanged in the female pups treated
      with dextromethorphan. These results suggest that dextromethorphan
      neuroprotection against ischemic injury in the immature brain is sex-dependent.

PMID- 16951578
TI  - Lithium alters regional rat brain myo-inositol at 2 and 4 weeks: an ex-vivo
      magnetic resonance spectroscopy study at 18.8 T.
AB  - Lithium has been the mainstay of treatment for bipolar disorder. Early studies
      suggest that lithium acts via inositol depletion. This study assesses the effect
      of 1, 2 and 4 weeks of lithium treatment on myo-inositol concentrations across
      several brain regions. Thirty-six Sprague-Dawley rats were treated for 2 weeks
      with an intraperitoneal injection of either 1 mmol/kg/day, twice daily lithium
      chloride (n=18) or placebo (2 ml/kg of saline) (n=18). The rats were separated
      into three groups: 1 week, 2 weeks and 4 weeks. Brains were dissected into
      prefrontal, temporal and occipital cortical areas, as well as hippocampus, and
      analyzed at 18.8 T. Myo-inositol was quantified using the Chenomx Profiler
      software. Lithium did not alter myo-inositol concentrations at 1 week. A
      significant reduction exists in myo-inositol concentrations in lithium-treated
      rats at 2 and 4 weeks, across all four brain regions. Studies suggest brain
      region-specific alterations in myo-inositol concentrations among bipolar
      patients. Our findings suggest that lithium-induced reduction of myo-inositol is
      more global.

PMID- 16951579
TI  - Low alpha-synuclein 126 mRNA levels in dementia with Lewy bodies and Alzheimer
      disease.
AB  - Alpha-synuclein, a main component of Lewy bodies in synucleinopathies and senile
      plaques in Alzheimer disease, is centrally involved in neurodegeneration. Three
      different isoforms (alpha-synuclein 112, 126, and 140) resulting from alternative
      splicing have been described so far. The present study explores alpha-synuclein
      126 mRNA expression levels in the prefrontal cortex of six patients with dementia
      with Lewy bodies, eight patients with Lewy body variant of Alzheimer disease,
      eight patients with Alzheimer disease, and 10 controls. Relative alpha-synuclein
      126 expression levels were determined by real-time polymerase chain reaction with
      competimer technology. Alpha-synuclein 126 mRNA expression was markedly decreased
      in the three dementias in comparison with controls, suggesting an important role
      of this alpha-synuclein isoform in the normal brain.

PMID- 16951580
TI  - GABAergic tonic inhibition of substantia gelatinosa neurons in mouse spinal cord.
AB  - We used whole-cell recording to identify, for the first time, GABAergic tonic
      current in subpopulations of substantia gelatinosa neurons in mouse spinal cord
      slices. Application of the gamma-aminobutyric acid type A receptor antagonist
      bicuculline revealed tonic currents in 49 of 73 substantia gelatinosa neurons.
      These tonic currents were dissected into three groups according to their diverse
      pharmacological properties. In the first group, furosemide failed to block the
      tonic current while midazolam and propofol potentiated it. In the second group,
      furosemide blocked the tonic current but midazolam and propofol failed to enhance
      the current. In the third group, furosemide blocked and 3alpha, 21-dihydroxy
      5alpha-pregnan-20-one enhanced the tonic current. The presence of mRNAs for
      alpha4, alpha5, delta and epsilon subunits in the substantia gelatinosa (reverse
      transcriptase polymerase chain reaction) suggest that gamma-aminobutyric acid
      type A receptors comprising alpha5betaxgamma2, alphaxbetaxepsilon and
      alpha4betaxdelta subunits are responsible for tonic currents.

PMID- 16951581
TI  - Estrogen dissociates Tau and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic
      acid receptor subunit in postischemic hippocampus.
AB  - During cerebral ischemia, part of the damage associated with the hyperactivation
      of glutamate receptors results from the hyperphosphorylation of the microtubule
      associated protein Tau. Previous studies have shown that estradiol treatment
      reduces neural damage after cerebral ischemia. Here, we show that transient
      occlusion of the middle cerebral artery results in the hyperphosphorylation of
      Tau and in a significant increase in the association of Tau with glycogen
      synthase kinase-3beta and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic
      acid type glutamate receptor subunits 2/3 in the hippocampus. Estradiol treatment
      decreased hippocampal injury, inhibited glycogen synthase kinase-3beta and
      decreased the hyperphosphorylation of Tau and the interaction of Tau with
      glycogen synthase kinase-3beta and alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid receptor. These findings suggest that ischemia produces a strong
      association between Tau and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic
      acid receptor, and estradiol can exert at least part of its neuroprotective
      activity through inhibition of glycogen synthase kinase-3beta.

PMID- 16951582
TI  - NR2B-containing N-methyl-D-aspartate subtype glutamate receptors regulate the
      acute stress effect on hippocampal long-term potentiation/long-term depression in
      vivo.
AB  - Behavioral stress facilitates long-term depression but impairs long-term
      potentiation in the hippocampus. Recent evidence in vitro demonstrates that the
      NR2B-containing N-methyl-D-aspartate subtype glutamate receptor antagonist Ro25
      6981 prevents the behavioral stress-facilitated hippocampal long-term depression.
      It is, however, unknown whether Ro25-6981 influences hippocampal long-term
      depression and long-term potentiation induction in vivo under stressful
      condition. Here, we found that infusion of Ro25-6981 (2.3 microg in 6 microl,
      intracerebroventricular for 10 min) 30 min before low-frequency stimulation
      prevented the facilitation of hippocampal long-term depression by acute stress in
      anesthetized adult rats. Moreover, infusion of Ro25-6981 30 min before high
      frequency stimulation reversed stress-impaired hippocampal long-term
      potentiation. These results suggest that the NR2B-containing N-methyl-D-aspartate
      subtype glutamate receptors are crucial for the effects of behavioral stress on
      hippocampal long-term depression and long-term potentiation in vivo.

PMID- 16951583
TI  - Are serotonin transporter knockout mice 'depressed'?: hypoactivity but no
      anhedonia.
AB  - Although the serotonin transporter is a key target for antidepressants, its exact
      role in depression etiology remains unclear. While serotonin transporter knockout
      mice are a potential model to examine this problem, their depression profile is
      unclear in several 'despair' tests, and may be confounded by their hypoactivity
      phenotype (confirmed here by marble-burying and bedding tests). To assess
      depression in these mice, we evaluated wild-type, heterozygous, and serotonin
      transporter knockout C57BL/6 male mice on a well-validated, anhedonia-based
      depression paradigm, the sucrose preference test. Overall, all three genotypes
      showed similar sucrose preference, indicating an unaltered hedonic state. These
      results demonstrate that depression-like behavior (unlike hypoactivity) is not a
      baseline phenotypic feature of serotonin transporter knockout mice, suggesting
      anew that these mice do not represent a genetic model of depression.

PMID- 16951584
TI  - Neural processes involved with perception of non-native durational contrasts.
AB  - Neural processes underlying identification of durational contrasts were studied
      by comparing English and Japanese speakers for Japanese short/long vowel
      identification relative to consonant identification. Enhanced activities for non
      native contrast (Japanese short/long vowel identification by English speakers)
      were observed in brain regions involved with articulatory-auditory mapping
      (Broca's area, superior temporal gyrus, planum temporale, and cerebellum), but
      not in the supramarginal gyrus. Greater activity in the supramarginal gyrus found
      for the consonant identification over short/long vowel identification by Japanese
      speakers implies that it is more important for phonetic contrasts differing in
      place of articulation than for vowel duration. These results support the
      hypothesis that neural processes used to facilitate perception depend on the
      relative contribution of information important for articulatory planning control.

PMID- 16951585
TI  - Neuroimaging of meditation's effect on brain reactivity to pain.
AB  - Some meditation techniques reduce pain, but there have been no studies on how
      meditation affects the brain's response to pain. Functional magnetic resonance
      imaging of the response to thermally induced pain applied outside the meditation
      period found that long-term practitioners of the Transcendental Meditation
      technique showed 40-50% fewer voxels responding to pain in the thalamus and total
      brain than in healthy matched controls interested in learning the technique.
      After the controls learned the technique and practiced it for 5 months, their
      response decreased by 40-50% in the thalamus, prefrontal cortex, total brain, and
      marginally in the anterior cingulate cortex. The results suggest that the
      Transcendental Meditation technique longitudinally reduces the
      affective/motivational dimension of the brain's response to pain.

PMID- 16951586
TI  - Spindle-shaped constriction and propagated dilation of arterioles during cortical
      spreading depression.
AB  - A dual illumination technique was used to examine the behavior of parenchymal
      arterioles of the cortex during cortical spreading depression in six cats. K+
      produced a wave-ring spread of optical density changes concentrically from the
      injection site. At locations where the wave was passing, arterioles first
      constricted at one or two spots (55+/-43% of control), forming a spindle-shape in
      the early phase of cortical spreading depression, and then markedly dilated
      (155+/-57% of control) within 1 min. The dilation started at the constricted
      spots, propagated bidirectionally and finally resulted in full-length dilation of
      the arteriole. Although it varied in magnitude and time-course, this arteriolar
      behavior was observed in all six cats. Despite these changes, no associated
      downstream tissue microvascular flow changes were discernable.

PMID- 16951596
TI  - Preventing salmonella infection.

PMID- 16951597
TI  - What is gastroparesis?

PMID- 16951598
TI  - Improving medication adherence with orally disintegrating tablets.

PMID- 16951599
TI  - Myths & facts...about women and cardiovascular disease.

PMID- 16951600
TI  - Heading off the pain of postherpetic neuralgia.

PMID- 16951603
TI  - What's the best way to secure a catheter?

PMID- 16951618
TI  - Patient education series. Advance directives.

PMID- 16951616
TI  - Weaning patients from mechanical: ventilation.

PMID- 16951619
TI  - Keep your older patients out of medication trouble.

PMID- 16951620
TI  - Rory's dream.

PMID- 16951621
TI  - First aid for bleeding wounds.

PMID- 16951622
TI  - Responding to trauma: your priorities in the first hour.

PMID- 16951624
TI  - How do you distinguish between grief and depression?

PMID- 16951625
TI  - Want to become a clinical nursing instructor?

PMID- 16951626
TI  - Infection control survey.

PMID- 16951633
TI  - Cost-cutting from the top.

PMID- 16951634
TI  - Combination drugs...

PMID- 16951635
TI  - Acute ischemic stroke.

PMID- 16951637
TI  - THE CLASSIC: The hazards of biopsy in patients with malignant primary bone and
      soft-tissue tumors. The Journal of Bone and Joint Surgery, 1982;64:1121-1127.

PMID- 16951639
TI  - The Classic: Epiphyseal chondromatous giant cell tumors of the upper end of the
      humerus. Surg Gynecol Obstet.1931;52:543.

PMID- 16951640
TI  - The Classic: On osteo-sarcoma, spina-ventosa, and tubercles in bone. Injuries and
      Diseases of Bones; 1847: 416-433.

PMID- 16951641
TI  - The Classic: Diffuse endothelioma of bone. Proceedings of the New York
      Pathological Society. 1921;12:17.

PMID- 16951642
TI  - Disadvantages of structured treatment interruption persist in patients with
      multidrug-resistant HIV-1: final results of the CPCRA 064 study.
AB  - BACKGROUND: We report the final results of Community Programs for Clinical
      Research on AIDS (CPCRA-064) study, a multicenter, prospective, randomized,
      controlled trial that determines the long-term clinical impact of structured
      treatment interruption (STI) in patients with multidrug-resistant (MDR) HIV-1.
      METHODS AND RESULTS: Two hundred seventy-four patients on stable antiretroviral
      therapy with MDR HIV-1 treatment failure were randomized to a 4-month STI,
      followed by an optimized antiretroviral regimen (STI arm, n = 140) or an
      immediate change to an optimized antiretroviral regimen (control arm, n = 134).
      Main outcome measures were progression of disease or death and changes from
      baseline in HIV RNA levels (log copies/mL) and CD4 cell counts (cells/mm). The
      median baseline HIV RNA level was 5.0 log copies/mL, the median CD4 count was 147
      cells/mm, and the nadir CD4 count was 32 cells/mm. The median follow-up was 37
      months. After the STI period, there were no differences in HIV RNA level
      responses between treatment arms. Differences in CD4 count responses always
      favored the control arm, with an advantage of 84 cells from 0 to 4 months (P <
      0.0001), 50 cells from 4 to 12 months (P < 0.0001), 45 cells from 12 to 24 months
      (P = 0.006), and 43 cells after 24 months (P = 0.07). Rates in the STI and
      control arms for first progression-of-disease event or death were 17.5 and 14.3,
      respectively (hazard ratio = 1.28; P = 0.22). CONCLUSION: STI before changing
      regimens in patients with MDR HIV-1 treatment failure has a prolonged negative
      impact on CD4 cell count recovery and does not confer progression of disease or
      virologic benefits.

PMID- 16951643
TI  - A once-daily lopinavir/ritonavir-based regimen provides noninferior antiviral
      activity compared with a twice-daily regimen.
AB  - OBJECTIVE: To evaluate the safety and noninferiority and to explore the efficacy
      of administration of once-daily versus twice-daily lopinavir/ritonavir (LPV/r) in
      antiretroviral-naive HIV-1-infected subjects. DESIGN: Randomized, open-label,
      multicenter, comparative study. METHODS: One hundred ninety antiretroviral-naive
      subjects with plasma HIV-1 RNA level >1000 copies/mL and any CD4 cell count were
      randomized to lopinavir/ritonavir at a dose of 800/200 mg administered once daily
      (n = 115) or lopinavir/ritonavir at a dose of 400/100 mg administered twice daily
      (n = 75). Subjects also received tenofovir disoproxil fumarate (TDF) at a dose of
      300 mg and emtricitabine (FTC) at a dose of 200 mg administered once daily.
      RESULTS: The median baseline plasma HIV-1 RNA level and CD4 count were 4.8 log10
      copies/mL and 216 cells/mm, respectively. Before week 48, 20% (once daily) and
      29% (twice daily) subjects discontinued. Virologic responses of the subjects
      through 48 weeks were comparable; 70% (once daily) and 64% (twice daily) achieved
      an HIV-1 RNA level <50 copies/mL by intent-to-treat, noncompleter = failure
      analysis. No subject demonstrated LPV or TDF resistance, but 3 subjects (2 in the
      once-daily group, 1 in the twice-daily group) demonstrated FTC resistance. Mean
      increases in CD4 count were similar. Diarrhea (16% in the once-daily group, 5% in
      the twice-daily group; P = 0.036) was the most common moderate or severe study
      drug-related adverse event. CONCLUSIONS: Through 48 weeks, a once-daily regimen
      of lopinavir/ritonavir + TDF + FTC appears to have similar virologic and
      immunologic responses in antiretroviral-naive subjects as the same regimen with
      lopinavir/ritonavir administered twice daily. Both regimens were relatively well
      tolerated, and no LPV or TDF resistance was observed.

PMID- 16951644
TI  - The occurrence of vaginal infections among HIV-infected and high-risk HIV
      uninfected women: longitudinal findings of the women's interagency HIV study.
AB  - OBJECTIVES: To evaluate changes over time in rates of bacterial vaginosis (BV),
      trichomoniasis (TV), and yeast vaginitis (YV) among HIV-infected and similar HIV
      uninfected women. METHODS: Two thousand fifty-six HIV-infected women and 554 HIV
      uninfected women were evaluated semiannually from 1994 until March 2003 in a
      prospective cohort study. BV was diagnosed by Gram stain, TV by wet mount, and YV
      by symptoms with microscopically visible hyphae or positive culture. Trends were
      assessed using Poisson models. RESULTS: At baseline, BV was present in 42.8% and
      47.0% of HIV-infected and uninfected women (P = 0.21), TV in 6.1% and 7.8% (P =
      0.17), and YV in 10.0% and 3.8% (P < 0.001). Over time, rates of BV and TV
      decreased significantly in both groups, whereas rates of YV declined only among
      HIV-infected women. Risk of BV was not associated with HIV status, whereas HIV
      infected women had a lower risk of TV. Highly active antiretroviral therapy
      (HAART) use was associated with decreased risk of all 3 infections. CONCLUSIONS:
      : Declines in BV, TV, and YV represent decreased morbidity for HIV-infected women
      and, potentially, decreased risk of transmission of HIV, because each has been
      associated with increased genital detection of HIV.

PMID- 16951645
TI  - Bathhouse-based voluntary counseling and testing is feasible and shows
      preliminary evidence of effectiveness.
AB  - The goal of this study was to provide evidence for the feasibility and
      effectiveness of conducting voluntary counseling and testing (VCT) for HIV in a
      bathhouse setting. Four hundred ninety-two men participated in bathhouse-based
      VCT offered at a single venue over a 13-month period. A convenience sample of 133
      of these testers was assessed at 2 points: immediately before and 3 months after
      testing. Thirty-eight percent of men in the sample reported unprotected anal
      intercourse (UAI) with 1 of their 2 most recent partners in the 3 months before
      testing, and 48% of those men had not otherwise been tested for HIV in the
      previous 12 months. Results showed that in the months after VCT, men were less
      likely to engage in UAI, decreased their frequency of engaging in sex while drunk
      or high, and were more likely to communicate about HIV with their sexual
      partners. Bathhouse-based VCT seems to be a feasible approach for reaching
      significant numbers of men at risk for HIV and shows preliminary evidence of
      effectiveness in changing some specific HIV-related risk and precautionary
      behaviors.

PMID- 16951646
TI  - Partner-specific sexual behavioral differences between phase 3 HIV vaccine
      efficacy trial participants and controls: Project VISION.
AB  - OBJECTIVE: To assess and compare sexual behaviors using partner-specific data
      between HIV-negative men who have sex with men (MSM) recruited for an HIV vaccine
      efficacy trial and a control group. METHODS: HIV-negative MSM from an HIV vaccine
      trial (n = 525) and controls (n = 732) were recruited by similar strategies and
      interviewed about behaviors with the 3 most recent partners in the past 6 months,
      obtained by audio computer-assisted self-interview (A-CASI). RESULTS: Vaccine
      trial participants were more likely than controls to report an HIV-positive
      partner (24.7% and 14.1%, respectively) or an HIV-positive primary partner (16.1%
      and 6.8%, respectively) and were less likely to report occasional or single-time
      partners of unknown HIV status (51.6% and 63.2%, respectively; P < 0.05 for each
      comparison). Vaccine trial participants more often reported receptive unprotected
      anal intercourse (UAI) during their last sexual encounter with an HIV-positive
      partner (adjusted odds ratio [OR] = 2.7, 95% confidence interval [CI]: 1.0 to
      7.9). Most believed their HIV-positive partners were receiving antiretroviral
      treatment (ART), however, and after adjustment for perceived ART use, the
      association between vaccine study participation and receptive UAI with an HIV
      positive partner was not significant. CONCLUSIONS: High-risk sexual behavior was
      reported by many VAX004 participants and controls. Differences between vaccine
      trial and control participants in the highest risk per contact behavior,
      receptive UAI with HIV-positive partners, was partly accounted for by perceived
      ART use. Partner level data are useful in refining risk assessment, which is
      important in the evaluation of HIV vaccine and other prevention trials.

PMID- 16951647
TI  - Factors associated with self-efficacy for condom use and sexual negotiation among
      South african youth.
AB  - OBJECTIVES: To use logistic regression modeling to identify factors associated
      with high self-efficacy for sexual negotiation and condom use in a sample of
      South African youth. METHODS: The Reproductive Health and HIV Research Unit
      (RHRU) National Youth Survey examined a nationally representative sample of 7409
      sexually active South African youth aged 15 to 24 years. We used logistic
      regression modeling in this sample to identify factors associated with the main
      outcome of high self-efficacy. RESULTS: Among female respondents (n = 3890),
      factors associated with high self-efficacy in the adjusted model were knowing how
      to avoid HIV (odds ratio [OR] = 2.30, 95% confidence interval [CI]: 1.05 to
      5.00), having spoken with someone other than a parent or guardian about HIV/AIDS
      (OR = 1.46, 95% CI: 1.01 to 2.10), and having life goals (OR = 1.28, 95% CI: 1.10
      to 1.48). Not using condoms during their first sexual encounter (OR = 0.61, 95%
      CI: 0.50 to 0.76), a history of unwanted sex (OR = 0.66, 95% CI: 0.51 to 0.86),
      and believing that condom use implies distrust in one's partner (OR = 0.57, 95%
      CI: 0.51 to 0.86) were factors associated with low self-efficacy among female
      respondents. Male respondents (n = 3519) with high self-efficacy were more likely
      to take HIV seriously (OR = 4.03, 95% CI: 1.55 to 10.52), to believe they are not
      at risk for HIV (OR = 1.38, 95% CI: 1.12 to 1.70), to report that getting condoms
      is easy (OR = 1.85, 95% CI: 1.23 to 2.77), and to have life goals (OR = 1.30, 95%
      CI: 1.10 to 1.54). Not using condoms during their first sexual experience (OR =
      0.51, 95% CI: 0.39 to 0.67), a history of having unwanted sex (OR = 0.47, 95% CI:
      0.34 to 0.64), believing condom use is a sign of not trusting one's partner (OR =
      0.63, 95% CI: 0.46 to 0.87), and refusing to be friends with HIV-infected persons
      (OR = 0.52, 95% CI: 0.32 to 0.85) were factors associated with low self-efficacy
      among male respondents in the fully adjusted model. CONCLUSIONS: We used the
      social cognitive model (SCM) to identify factors associated with self-efficacy
      for condom use and sexual negotiation. Many of these factors are modifiable and
      suggest potential ways to improve self-efficacy and reduce HIV sexual risk
      behavior in South African youth.

PMID- 16951648
TI  - Modeling the impact of a partially effective HIV vaccine on HIV infection and
      death among women and infants in South Africa.
AB  - OBJECTIVE: To assess the potential impact over 10 years of a partially effective
      HIV vaccine in a cohort of 15-year-old adolescent girls in South Africa in terms
      of HIV infections and deaths prevented in mothers and infants. METHODS: A
      computer simulation was constructed using a population of all 15-year-old
      adolescent girls in South Africa followed for 10 years. A partially effective
      vaccine is introduced into this population with the ability to reduce the HIV
      incidence rates of the adolescents and vertical transmission to their infants
      through birth and breast-feeding. At the end of this 10 year period, the number
      of HIV infections and death prevented in adolescents and infants is analyzed.
      RESULTS: Using a 5% HIV incidence rate, a 50% effective vaccine decreases the
      number of HIV cases among adolescents by 57,653 (28.7%) and the number of cases
      among infants by 13,765 (28.9%) over 10 years. In addition, assuming a vaccine
      cost of $20 per dose, the vaccination program can save approximately $120 million
      for the South African government over 10 years. CONCLUSION: A partially effective
      HIV vaccine has an important role in HIV prevention in adolescents and infants in
      South Africa irrespective of other public policy implementations.

PMID- 16951649
TI  - Botswana's Tebelopele voluntary HIV counseling and testing network: use and
      client risk factors for HIV infection, 2000-2004.
AB  - BACKGROUND: : HIV services, including voluntary counseling and testing (VCT) and
      antiretroviral (ARV) therapy, expanded rapidly in Botswana from 2000 through
      2004. METHODS: : Client data from Botswana's Tebelopele VCT network were analyzed
      to describe clients, factors associated with HIV infection, and trends in VCT
      use. RESULTS: : Tebelopele provided free, anonymous, same-day HIV tests for
      117,234 clients from 2000 through 2004. Before ARV therapy was available, 8.3% of
      clients sought a test because of illness, and 26.3% were HIV-positive. After ARV
      therapy became available, 20.1% of clients sought a test because of illness, and
      38.8% were HIV-positive. Most VCT clients (82.7%) were unmarried; 89.8% reported
      no or 1 sexual partner in the last 3 months; and 50.2% of unmarried clients
      reported always using condoms in the last 3 months. In multivariate analysis,
      higher educational level, marriage, and always using condoms were associated with
      a lower risk of HIV. Having only 1 recent sexual partner was associated with less
      condom use and a higher risk of being HIV-positive for men. CONCLUSIONS: : VCT
      has been well accepted in Botswana. Analysis of this data set supports efforts to
      promote 100% condom use and to emphasize that partner reduction must be combined
      with condom use and HIV testing to protect against HIV.

PMID- 16951650
TI  - The cost-effectiveness of treating male trichomoniasis to avert HIV transmission
      in men seeking sexually transmitted disease care in Malawi.
AB  - OBJECTIVE: Allocation of funds to program areas where they may have an impact is
      critical to the success of any HIV control program. We examined the cost
      effectiveness of providing first-line treatment for male trichomoniasis in
      Malawi, a condition not commonly considered in syndromic management throughout
      sub-Saharan Africa. METHODS: We used decision tree analysis to assess program
      costs and outcomes among a 1-year population of male sexually transmitted disease
      (STD) clinic attendees estimated at 10,000 in Lilongwe. Our main outcomes were
      program costs from the government perspective and HIV infections averted. We
      conducted univariate and multivariate sensitivity analyses on selected
      parameters. RESULTS: In our study population of male STD clinic attendees with an
      HIV prevalence of 44% and a Trichomonas vaginalis prevalence of 20%, including
      universal metronidazole as a first-line treatment for trichomoniasis at $0.05 per
      dose would increase program costs by $277 (year 2000 US dollars) and avert 23
      cases of HIV. The incremental cost-effectiveness ratio (ICER) over the current
      STD management guidelines was $15.42 per case of HIV averted. The number of HIV
      infections averted under sensitivity analysis ranged from 2 to 52, with attendant
      ICERs varying from cost savings to $162.92. Consideration of wider social
      benefits, such as the costs of HIV infections to the individual or the
      government, would further enhance the cost-effectiveness of this program.
      CONCLUSIONS: As part of a larger program to control STDs, incorporating
      metronidazole to treat male trichomoniasis could represent a cost-effective means
      to reduce HIV transmission in this high-risk group.

PMID- 16951651
TI  - gp120-independent HIV infection of cells derived from the female reproductive
      tract, brain, and colon.
AB  - The infection of CD4 cells may have significant involvement in the transmission
      and long-term persistency of HIV. Using HIV clones carrying the enhanced green
      fluorescent protein (EGFP), we infected epithelial and glioneuronal cell lines
      derived from the female reproductive tract, brain, colon, and intestine. HIV
      infection was quantified by counting EGFP-positive cells. Infection was
      quantified in cell lines from the female reproductive tract, brain tissue, and
      colon tissue (0.36%-3.15%). Virus replicated in the infected cells and the
      progeny virus were infectious for CD4 cells, HeLa-CD4, and CEM T lymphocytes.
      Furthermore, we found that infection of these epithelial and brain cell lines is
      independent of gp120. The results from the infection of CD4 epithelial cells
      suggest that HIV can traverse epithelial cell layers by infecting them through a
      gp120-independent mechanism. Infection of glial and neuronal cell lines suggests
      that HIV infection of these cells is a probable mechanism for HIV pathogenicity
      in the brain and a possible cause for persistent infection in patients.

PMID- 16951653
TI  - Towards a paradigm shift in neuropsychiatry.

PMID- 16951652
TI  - Diversity of HIV in rural Burkina Faso.
AB  - SUMMARY: : On introduction of a program for prevention of mother-to-child
      transmission (PMTCT) of HIV in Nouna, rural Burkina Faso, we determined HIV
      prevalence in this region to be 3.6%, which is significantly lower than the 7%
      reported for 2 major cities of Burkina Faso. Forty-three samples from drug-naive
      pregnant women and patients before introduction of antiretroviral therapy (ART)
      were genotypically characterized in gag, pol, and env regions. One individual
      each was infected with HIV-2 or dually infected with HIV-1 and HIV-2. The most
      dominant HIV-1 subtypes were CRF02_AG and CRF06_cpx, similar to what has been
      observed in other West African countries. A discordant genotype was observed in
      almost half of the analyzed samples, with most putative recombinants deriving
      from CRF02_AG and CRF06_cpx. Recently reported strains like the CRF09_cpx and the
      sub-subtype A3 as well as some unique recombinant forms of HIV like D/D/CRF02_AG
      and CRF02_AG/CRF02.AG/CRF_09cpx were also detected. Analysis of drug resistance
      associated polymorphisms detected the nonnucleoside reverse transcriptase
      inhibitor (NNRTI) resistance mutations K103N/E and V118I in 1 individual each,
      suggesting transmission of drug-resistant viruses or prior use of antiretroviral
      drugs. Resistance-associated polymorphisms (K20I and M36I) were prevalent in the
      complete protease (PR) region, but no primary drug resistance mutations were
      detected. Analysis of the HR1 and HR2 regions of gp41, important for T-20
      sensitivity, revealed no known resistance mutations but several polymorphisms of
      unknown importance. Monitoring for drug resistance mutations among naive subjects
      is important in this area on introduction of antiretroviral drugs.

PMID- 16951654
TI  - Is obsessive-compulsive disorder caused by a second-messenger imbalance?
AB  - Although the precise etiologic nature of obsessive-compulsive disorder (OCD), one
      of the most common psychiatric conditions, is unknown, several findings indicate
      involvement of the serotonin (5-HT) transporter. Apart from the specific effects
      of selective 5-HT reuptake inhibitors, other studies show decreased functionality
      of the platelet 5-HT transporter in OCD. In this report, the authors combine data
      from two independent studies of patients with OCD, showing both an increased
      activity of protein kinase type C (PKC) and a decreased activity of protein
      kinase type A (PKA). The authors propose a unifying hypothesis that OCD might be
      determined by an imbalance between PKC and PKA, with a prevalence of the former
      and, more generally, of the phosphoinositide over the cyclic adenosine
      monophosophate (cAMP) pathway. Should this hypothesis prove correct, the path
      would be open for new therapeutic interventions in the treatment of OCD.

PMID- 16951655
TI  - Electroretinogram B-wave amplitude in panic disorder.
AB  - Abnormal light-related behaviors have been described for patients with panic
      disorder (PD). The present study was undertaken to investigate the retinal light
      response in PD using electroretinography (ERG). The authors conducted b-wave ERG
      measurements with a bright light (after dark adaptation) in 28 patients with PD
      and 28 control subjects. There were no significant differences in the mean b-wave
      amplitude between the two groups, but the retinal response to light in PD
      patients was generally lower than in healthy subjects. A large interindividual
      variability was found; also noted was a significant difference in the mean b-wave
      amplitude between the right and left eyes in the control group. The data indicate
      subtle variation of retinal photosensitivity in a subgroup of patients with PD.
      Because dopaminergic retinal activity affects b-ERG amplitude, the authors
      hypothesize that the dopaminergic system is involved in the response to light in
      PD patients.

PMID- 16951656
TI  - A magnetic resonance imaging study of regional cortical volumes following
      stereotactic anterior cingulotomy.
AB  - The purpose of this study was to test the hypothesis that orbitofrontal cortical
      volume would be reduced following anterior cingulotomy for obsessive-compulsive
      disorder (OCD). Whole brain cortical parcellation was performed on magnetic
      resonance imaging (MRI) data from nine patients, before and 9 (+/-6) months
      following anterior cingulotomy. No significant volumetric reductions were found
      in the orbitofrontal cortex. Exploratory findings of reduced volume in ventral
      temporo-fusiform and posterior cingulate regions were consistent with chance
      differences, in the face of multiple comparisons. Therefore, though the
      circumscribed lesions of anterior cingulotomy have recently been associated with
      corresponding volumetric reductions in the caudate nucleus, no comparable
      volumetric reductions are evident in cortical territories. Taken together, these
      results are most consistent with a model of cingulo-striatal perturbation as a
      putative mechanism for the efficacy of this procedure. While limitations in
      sensitivity may have also contributed to these negative findings, the methods
      employed have previously proven sufficient to detect cortical volumetric
      abnormalities in OCD. The current results may reflect a relatively diffuse
      pattern of cortico-cortical connections involving the neurons at the site of
      cingulotomy lesions. Future functional neuroimaging studies are warranted to
      assess possible cortical or subcortical metabolic changes associated with
      anterior cingulotomy, as well as predictors of treatment response.

PMID- 16951657
TI  - The "prodromal" patient: both symptomatic and at-risk.
AB  - This article discusses conceptual issues relevant to the prospective diagnosis of
      the schizophrenic prodrome. Recent efforts to diagnose these patients with
      operational criteria based on current symptoms are reviewed. Symptomatic patients
      so identified appear to be treatment-seeking and to have mild cognitive
      impairments. In addition to being currently symptomatic, these patients are
      imminently at risk for progression of illness and development of schizophrenia.
      Data from three international centers suggest that this risk is approximately 40%
      over the next year of follow-up if untreated. The implications of the reviewed
      data for the appropriateness of the term "prodromal" and for treatment/prevention
      research for these patients are discussed.

PMID- 16951658
TI  - The timing of neurodevelopmental abnormality in schizophrenia: an integrative
      review of the neuroimaging literature.
AB  - In this paper we will review recent neuroimaging research in schizophrenia, with
      an aim to critically evaluate several recent proposals concerning the nature and
      the timing of the neuroanatomic abnormalities underlying the disorder.
      Specifically, enlargement of cerebrospinal fluid spaces, deficits in cortical
      gray matter, and reduced volume of mesiotemporal structures have all been
      reported in patients in the first episode of schizophrenia, their first-degree
      relatives, and individuals with schizotypal personality disorder, supporting the
      possibility that these abnormalities reflect a genetically mediated
      neurodevelopmental disorder. These findings from the empirical literature will be
      synthesized from the perspective of dual cytoarchitectonic trends theory of
      neurodevelopment, as well as in relation to current conceptions of the
      schizophrenia prodrome. We believe that the evidence shows that sufficient
      groundwork has been laid to begin longitudinal neuroimaging studies of
      adolescents at clinical risk for schizophrenia, in order to more definitively
      determine the pathophysiology of the disorder. Such information could have
      significant implications in terms of understanding the prediction, treatment, and
      ultimately the prevention of schizophrenia.

PMID- 16951659
TI  - "Hit me with your best shot... Fire away!".

PMID- 16951660
TI  - Should we incorporate psychological care into the management of IBS?

PMID- 16951661
TI  - Is coffee or tea good for your liver?

PMID- 16951662
TI  - Helicobacter pylori infection relapse after eradication is not a problem in
      developed countries.

PMID- 16951663
TI  - How safe and useful are left-lobe grafts in living donor liver transplantation?

PMID- 16951664
TI  - What is the clinical importance of small polyps with regard to colorectal cancer
      screening?

PMID- 16951665
TI  - How effective is itopride for the treatment of patients with functional
      dyspepsia?

PMID- 16951666
TI  - Treatment of intestinal failure: home parenteral nutrition.
AB  - Intestinal failure can result from surgical resection, obstruction, dysmotility,
      congenital deficiencies or disease-associated loss of absorption. Before the
      development of intravenous feeding in the late 1960s, the condition was fatal,
      but by the 1990s approximately 40,000 patients were being successfully managed on
      long-term home parenteral nutrition (HPN) annually in the US. Survival on HPN
      depends on the nature of the underlying medical condition: over 80% of Crohn's
      disease patients survive for 5 years, but only 20% of cancer patients survive for
      1 year. Although a patient's nutritional status is easy to maintain, there are
      serious long-term complications that arise from bypassing the gut and infusing
      nutrients directly into the systemic circulation. Catheter sepsis occurs about
      once per year (range 0-12 times). Abnormalities in liver function tests are
      common, but end-stage liver disease is rare. Central venous thrombosis develops
      in nearly all patients after 5 years. Although approximately 80% of patients on
      HPN are completely rehabilitated at home, their quality of life is impaired by
      the perpetual dependence on nocturnal intravenous infusions (every 8-12 h). In
      conclusion, HPN has allowed patients with previously fatal intestinal failure to
      survive and lead relatively normal lives at home, but their quality of life
      remains impaired by the dependence on intravenous infusions and complications
      that progress with time.

PMID- 16951668
TI  - Mechanisms of disease: immunopathogenesis of celiac disease.
AB  - Celiac disease is a genetic inflammatory disorder with autoimmune components that
      is induced by the ingestion of dietary gluten. Refractory sprue and enteropathy
      associated T-cell lymphoma are rare but distinctive complications of the disease.
      Although the importance of the adaptive immune response to gluten has been well
      established, observations now also point towards a central role for the gluten
      induced innate stress response in the pathogenesis of celiac disease and its
      malignant complications.

PMID- 16951667
TI  - Nonmalignant portal vein thrombosis in adults.
AB  - Portal vein thrombosis (PVT) consists of two different entities: acute PVT and
      chronic PVT. Acute PVT usually presents as abdominal pain. When the thrombus
      extends to the mesenteric venous arches, intestinal infarction can occur. Chronic
      PVT is usually recognized after a fortuitous diagnosis of hypersplenism or portal
      hypertension, or when there are biliary symptoms related to portal
      cholangiopathy. Local risk factors for PVT, such as an abdominal inflammatory
      focus, can be identified in 30% of patients with acute PVT; 70% of patients with
      acute and chronic PVT have a general risk factor for PVT, most commonly
      myeloproliferative disease. Early initiation of anticoagulation therapy for acute
      PVT is associated with complete and partial success in 50% and 40% of patients,
      respectively. A minimum of 6 months' anticoagulation therapy is recommended for
      the treatment of acute PVT. For patients with either form of PVT, permanent
      anticoagulation therapy should be considered if they have a permanent risk
      factor. In patients with large varices, beta-adrenergic blockade or endoscopic
      therapy seems to prevent bleeding as a result of portal hypertension, even in
      patients on anticoagulation therapy. In patients with jaundice or recurrent
      biliary symptoms caused by cholangiopathy, insertion of a biliary endoprosthesis
      is the first treatment option. Overall, the long-term outcome for patients with
      PVT is good, but is jeopardized by cholangiopathy and transformation of
      underlying myeloproliferative disease into myelofibrosis or acute leukemia.

PMID- 16951669
TI  - Hepatic adenomatosis in a young woman with glucose intolerance.
AB  - BACKGROUND: A 30-year-old white woman presented to our department in December
      2004 for clinical evaluation of episodic, severe, right upper quadrant pain. She
      was otherwise healthy and her only medication was a daily oral contraceptive
      pill. Her past medical history was notable for gestational diabetes and fasting
      hyperglycemia since her pregnancy. Family history was significant for a younger
      sister with diabetes mellitus, but no known family history of liver disease.
      INVESTIGATIONS: Physical examination, laboratory investigations, multiphasic CT
      scan of the abdomen, exploratory laparotomy with biopsies. DIAGNOSIS: Hepatic
      adenomatosis. MANAGEMENT: Subsegmental hepatic resection followed by interval,
      long-term follow-up with hepatic imaging.

PMID- 16951670
TI  - Respiratory bronchiolitis-associated interstitial lung disease with fibrosis is a
      lesion distinct from fibrotic nonspecific interstitial pneumonia: a proposal.
AB  - Nine cases of clinical and radiographic chronic interstitial lung disease are
      presented that have features of respiratory bronchiolitis-associated interstitial
      lung disease, but were associated with a respiratory bronchiolitis having
      extensive paucicellular lamellar eosinophilic collagenous thickening of alveolar
      septa in a patchy, particularly subpleural distribution. Patients were middle
      aged with shortness of breath, mixed obstructive and restrictive lung disease
      with markedly reduced diffusing capacity and radiographs demonstrating
      centrilobular micronodules, occasional ground glass opacities and emphysema. All
      were alive at follow-up. The morphology of this process raises the differential
      diagnosis with the fibrotic form of nonspecific interstitial pneumonia and
      highlights the role of cigarette smoking as a potential cause of fibrotic lung
      disease.

PMID- 16951671
TI  - Divergent pathway of intestinal metaplasia and cystitis glandularis of the
      urinary bladder.
AB  - Intestinal metaplasia has been proposed to be a precursor lesion of
      adenocarcinoma in the urinary bladder. CDX2 is a transcription factor that is
      encoded by a homeotype gene that plays an essential role in the differentiation
      and proliferation of intestinal epithelial cells. Hepatocyte-specific antigen
      (Hep) has also been shown to be a useful marker of intestinal metaplasia. Tissues
      from 46 patients, including 22 cases of intestinal metaplasia of the urinary
      bladder, 11 cases of typical cystitis glandularis, and 13 cases containing both
      lesions, were selected and immunohistochemical stains for CDX2, Hep, cytokeratin
      20 (CK20), and cytokeratin 7 (CK7) were performed. Nuclear staining for CDX2 was
      observed in 29 of 35 (83%) cases of intestinal metaplasia of the urinary bladder.
      In contrast, nuclear staining for CDX2 was not observed in any case of typical
      cystitis glandularis; however, seven of 24 (29%) cases showed aberrant
      cytoplasmic expression in a mean of 37% of cells. CK20 was expressed in 28 of 35
      (80%) cases of intestinal metaplasia, but was observed in only one of 24 (4%)
      cases of cystitis glandularis in 15% of cells. CK7 was expressed in only six of
      35 (17%) cases of intestinal metaplasia, whereas expression of CK7 was observed
      in all cases (100%) of typical cystitis glandularis with a mean percentage of
      positively staining cells of 63%. The mean percentages of positively staining
      cells in intestinal metaplasia with CDX2, CK20, and CK7 were 55, 49, and 53%,
      respectively. All examples of both intestinal metaplasia and typical cystitis
      glandularis were uniformly negative for Hep. In the urinary bladder, intestinal
      metaplasia and typical cystitis glandularis have sharply contrasting
      immunoprofiles. Additionally, the absence of Hep staining in intestinal
      metaplasia of the urinary bladder, despite its morphologic resemblance to normal
      colonic mucosa and intestinal metaplasia in other organs, may signify the
      presence of unique metaplastic pathways in the urinary bladder.

PMID- 16951672
TI  - Cellular swirls in fine needle aspirates of papillary thyroid carcinoma: a new
      diagnostic criterion.
AB  - No single cytologic feature is specifically diagnostic for papillary thyroid
      carcinoma. We report herein the presence of swirl-like cellular aggregates in
      fine needle aspirates of papillary thyroid carcinoma but not in other thyroid
      entities. Cellular swirls are defined as concentrically organized aggregates of
      tumor cells in which many of the most peripherally situated cells have ovoid
      rather than round nuclei that are oriented perpendicular to the radius of the
      swirl. One hundred Papanicolaou- and/or Diff-Quik-stained FNAs of the thyroid
      diagnosed as papillary carcinoma, including seven fine needle aspirates of
      cervical lymph nodes showing metastatic papillary carcinoma, with or without cell
      blocks, were reviewed for the presence of cellular swirls. An additional 100
      thyroid FNAs, similarly stained and prepared, diagnosed as nodular goiter,
      Hashimoto's thyroiditis and follicular neoplasm were also reviewed for the
      presence of cellular swirls. Cellular swirls were easily observed at screening
      magnification and confirmed at high magnification. Seventeen of 100 FNAs (17%) of
      papillary carcinoma contained cellular swirls. No cases diagnosed as nodular
      goiter, Hashimoto's thyroiditis or follicular neoplasm contained these
      structures. Thirteen cases with swirls had histologic follow-up. These comprised
      seven papillary carcinomas with classical histopathology, two designated
      'differentiated papillary carcinoma,' two with follicular variant histopathology;
      one with a minor component of follicular variant histopathology; one papillary
      carcinoma metastatic to a cervical lymph node with classic histopathology. Swirls
      occurred in cases with relatively little pleomorphism, or in well-differentiated
      regions of papillary carcinoma that also displayed less well-differentiated
      components. Cellular swirls are a finding that is highly specific to papillary
      thyroid carcinoma. They are easily seen at screening magnification. Their
      presence in a FNA specimen may be helpful in cases where classic criteria for
      papillary thyroid carcinoma are scarce, particularly in well-differentiated
      papillary thyroid carcinoma. While the size and scope of this study are
      insufficient to conclude that cellular swirls alone are diagnostic of papillary
      thyroid carcinoma in the absence of other criteria, we believe these structures
      should be added to the list of diagnostic criteria.

PMID- 16951673
TI  - Activation of c-jun N-terminal kinase is associated with cell proliferation and
      shorter relapse-free period in superficial spreading malignant melanoma.
AB  - Signaling pathways regulating cell proliferation and survival have become
      attractive targets for anticancer strategies. In the present study, we analyzed
      by immunohistochemistry, a panel of benign nevi, superficial spreading and
      nodular primary melanomas and metastases for expression of activated p38/mitogen
      activated protein kinase (p-p38) and c-jun N-terminal kinase (JNK) (p-JNK) and
      correlated the findings with known prognostic variables. Twenty-five and 35% of
      the primaries and 9 and 25% of the metastases expressed variable levels of p-p38
      and p-JNK, respectively. In benign nevi, 73.5% expressed p-JNK and 7% expressed p
      p38. For patients with superficial spreading melanomas, high level of cytoplasmic
      p-JNK was associated with thicker tumors (P=0.017) and shorter disease-free
      survival (P=0.003) as well as with markers of cell proliferation (cyclin A
      (P=0.017) and p21 (P=0.021)). In nodular melanomas, nuclear p-p38 was associated
      with Ki-67 (P=0.012), but neither cytoplasmic nor nuclear localized p-p38 was
      associated with disease outcome. Of note, in superficial spreading melanomas, a
      positive correlation between cytoplasmic p-JNK and cytoplasmic p-extracellular
      signal-regulated kinase ERK(1/2) (P=0.005) and p-p38 (P=0.003) was observed.
      Likewise, p-p38 in cytoplasm was positively associated with cytoplasmic p-ERK1/2
      (P<0.0005) and p-Akt (P=0.047). In contrast, except for a positive correlation
      between nuclear p-p38 and membranous p-TrkA (P=0.02), no correlation between the
      activation status of the different signaling pathways was observed in nodular
      melanomas. In conclusion, our results suggest that in benign nevi activated JNK
      may have a role in restricting uncontrolled cell proliferation or survival.
      However, during tumor progression, activation of JNK is associated with cell
      proliferation and shorter relapse-free period for patients with superficial
      spreading melanomas, suggesting that the JNK activation status could be a marker
      for clinical outcome in at least a subgroup of malignant melanoma. In contrast,
      activation of p38 seems to play a less important role in development and
      progression of malignant melanomas.

PMID- 16951674
TI  - Molecular computational elements encode large populations of small objects.
AB  - Since the introduction of molecular computation, experimental molecular
      computational elements have grown to encompass small-scale integration,
      arithmetic and games, among others. However, the need for a practical application
      has been pressing. Here we present molecular computational identification (MCID),
      a demonstration that molecular logic and computation can be applied to a widely
      relevant issue. Examples of populations that need encoding in the microscopic
      world are cells in diagnostics or beads in combinatorial chemistry (tags). Taking
      advantage of the small size (about 1 nm) and large 'on/off' output ratios of
      molecular logic gates and using the great variety of logic types, input chemical
      combinations, switching thresholds and even gate arrays in addition to colours,
      we produce unique identifiers for members of populations of small polymer beads
      (about 100 microm) used for synthesis of combinatorial libraries. Many millions
      of distinguishable tags become available. This method should be extensible to far
      smaller objects, with the only requirement being a 'wash and watch' protocol. Our
      focus on converting molecular science into technology concerning analog sensors,
      turns to digital logic devices in the present work.

PMID- 16951675
TI  - Ambient pressure colossal magnetocaloric effect tuned by composition in Mn(1
      x)Fe(x)As.
AB  - The magnetocaloric effect (MCE) is the basis for magnetic refrigeration, and can
      replace conventional gas compression technology due to its superior efficiency
      and environment friendliness. MCE materials must exhibit a large temperature
      variation in response to an adiabatic magnetic-field variation and a large
      isothermal entropic effect is also expected. In this respect, MnAs shows the
      colossal MCE, but the effect appears under high pressures. In this work, we
      report on the properties of Mn(1-x)Fe(x)As that exhibit the colossal effect at
      ambient pressure. The MCE peak varies from 285 K to 310 K depending on the Fe
      concentration. Although a large thermal hysteresis is observed, the colossal
      effect at ambient pressure brings layered magnetic regenerators with huge
      refrigerating power closer to practical applications around room temperature.

PMID- 16951676
TI  - Electrical control of antiferromagnetic domains in multiferroic BiFeO3 films at
      room temperature.
AB  - Multiferroic materials, which offer the possibility of manipulating the magnetic
      state by an electric field or vice versa, are of great current interest. In this
      work, we demonstrate the first observation of electrical control of
      antiferromagnetic domain structure in a single-phase multiferroic material at
      room temperature. High-resolution images of both antiferromagnetic and
      ferroelectric domain structures of (001)-oriented multiferroic BiFeO3 films
      revealed a clear domain correlation, indicating a strong coupling between the two
      types of order. The ferroelectric structure was measured using piezo force
      microscopy, whereas X-ray photoemission electron microscopy as well as its
      temperature dependence was used to detect the antiferromagnetic configuration.
      Antiferromagnetic domain switching induced by ferroelectric polarization
      switching was observed, in agreement with theoretical predictions.

PMID- 16951677
TI  - Observation and tuning of hypersonic bandgaps in colloidal crystals.
AB  - Composite materials with periodic variations of density and/or sound velocities,
      so-called phononic crystals, can exhibit bandgaps where propagation of acoustic
      waves is forbidden. Phononic crystals are the elastic analogue of the well
      established photonic crystals and show potential for manipulating the flow of
      elastic energy. So far, the experimental realization of phononic crystals has
      been restricted to macroscopic systems with sonic or ultrasonic bandgaps in the
      sub-MHz frequency range. In this work, using high-resolution Brillouin
      spectroscopy we report the first observation of a hypersonic bandgap in face
      centred-cubic colloidal crystals formed by self-assembly of polystyrene
      nanoparticles with subsequent fluid infiltration. Depending on the particle size
      and the sound velocity in the infiltrated fluid, the frequency and the width of
      the gap can be tuned. Promising technological applications of hypersonic
      crystals, ranging from tunable filters and heat management to acousto-optical
      devices, are anticipated.

PMID- 16951678
TI  - Origin of defect-insensitive emission probability in In-containing (Al,In,Ga)N
      alloy semiconductors.
AB  - Group-III-nitride semiconductors have shown enormous potential as light sources
      for full-colour displays, optical storage and solid-state lighting. Remarkably,
      InGaN blue- and green-light-emitting diodes (LEDs) emit brilliant light although
      the threading dislocation density generated due to lattice mismatch is six orders
      of magnitude higher than that in conventional LEDs. Here we explain why In
      containing (Al,In,Ga)N bulk films exhibit a defect-insensitive emission
      probability. From the extremely short positron diffusion lengths (<4 nm) and
      short radiative lifetimes of excitonic emissions, we conclude that localizing
      valence states associated with atomic condensates of In-N preferentially capture
      holes, which have a positive charge similar to positrons. The holes form
      localized excitons to emit the light, although some of the excitons recombine at
      non-radiative centres. The enterprising use of atomically inhomogeneous crystals
      is proposed for future innovation in light emitters even when using defective
      crystals.

PMID- 16951679
TI  - Biological function of unannotated transcription during the early development of
      Drosophila melanogaster.
AB  - Many animal and plant genomes are transcribed much more extensively than current
      annotations predict. However, the biological function of these unannotated
      transcribed regions is largely unknown. Approximately 7% and 23% of the detected
      transcribed nucleotides during D. melanogaster embryogenesis map to unannotated
      intergenic and intronic regions, respectively. Based on computational analysis of
      coordinated transcription, we conservatively estimate that 29% of all unannotated
      transcribed sequences function as missed or alternative exons of well
      characterized protein-coding genes. We estimate that 15.6% of intergenic
      transcribed regions function as missed or alternative transcription start sites
      (TSS) used by 11.4% of the expressed protein-coding genes. Identification of P
      element mutations within or near newly identified 5' exons provides a strategy
      for mapping previously uncharacterized mutations to their respective genes.
      Collectively, these data indicate that at least 85% of the fly genome is
      transcribed and processed into mature transcripts representing at least 30% of
      the fly genome.

PMID- 16951680
TI  - Indian hedgehog is a major mediator of progesterone signaling in the mouse
      uterus.
AB  - The hedgehog family of morphogens are regulators of cell proliferation,
      differentiation and cell-cell communication. These morphogens have been shown to
      have important roles in organogenesis, spermatogenesis, stem cell maintenance and
      oncogenesis. Indian hedgehog (encoded by Ihh) has been shown to be expressed in
      the uterine epithelium under the control of the steroid hormone, progesterone.
      Although in vivo and in vitro studies have shown that progesterone achieves its
      effects on uterine function through epithelial-stromal cross-talk, molecular
      mediator(s) for this cellular communication pathway have not been elucidated.
      Using new experimental approaches that ablate Ihh specifically in Pgr-positive
      uterine cells of the mouse, we demonstrate that Ihh is an essential mediator of
      Pgr action in the uterus, and expression of this factor is critical in mediating
      the communication between the uterine epithelium and stroma required for embryo
      implantation.

PMID- 16951681
TI  - Lamin B1 duplications cause autosomal dominant leukodystrophy.
AB  - Adult-onset autosomal dominant leukodystrophy (ADLD) is a slowly progressive
      neurological disorder characterized by symmetrical widespread myelin loss in the
      central nervous system, with a phenotype similar to chronic progressive multiple
      sclerosis. In this study, we identify a genomic duplication that causes ADLD.
      Affected individuals carry an extra copy of the gene for the nuclear laminar
      protein lamin B1, resulting in increased gene dosage in brain tissue from
      individuals with ADLD. Increased expression of lamin B1 in Drosophila
      melanogaster resulted in a degenerative phenotype. In addition, an abnormal
      nuclear morphology was apparent when cultured cells overexpressed this protein.
      This is the first human disease attributable to mutations in the gene encoding
      lamin B1. Antibodies to lamin B are found in individuals with autoimmune
      diseases, and it is also an antigen recognized by a monoclonal antibody raised
      against plaques from brains of individuals with multiple sclerosis. This raises
      the possibility that lamin B may be a link to the autoimmune attack that occurs
      in multiple sclerosis.

PMID- 16951682
TI  - Deficiency of hyccin, a newly identified membrane protein, causes hypomyelination
      and congenital cataract.
AB  - We describe a new autosomal recessive white matter disorder ('hypomyelination and
      congenital cataract') characterized by hypomyelination of the central and
      peripheral nervous system, progressive neurological impairment and congenital
      cataract. We identified mutations in five affected families, resulting in a
      deficiency of hyccin, a newly identified 521-amino acid membrane protein. Our
      study highlights the essential role of hyccin in central and peripheral
      myelination.

PMID- 16951683
TI  - Heritable germline epimutation of MSH2 in a family with hereditary nonpolyposis
      colorectal cancer.
AB  - Epimutations in the germline, such as methylation of the MLH1 gene, may
      contribute to hereditary cancer syndrome in human, but their transmission to
      offspring has never been documented. Here we report a family with inheritance, in
      three successive generations, of germline allele-specific and mosaic
      hypermethylation of the MSH2 gene, without evidence of DNA mismatch repair gene
      mutation. Three siblings carrying the germline methylation developed early-onset
      colorectal or endometrial cancers, all with microsatellite instability and MSH2
      protein loss. Clonal bisulfite sequencing and pyrosequencing showed different
      methylation levels in different somatic tissues, with the highest level recorded
      in rectal mucosa and colon cancer tissue, and the lowest in blood leukocytes.
      This mosaic state of germline methylation with different tissue distribution
      could act as the first hit and provide a mechanism for genetic disease
      inheritance that may deviate from the mendelian pattern and be overlooked in
      conventional leukocyte-based genetic diagnosis strategy.

PMID- 16951684
TI  - Cholesterol glucosylation promotes immune evasion by Helicobacter pylori.
AB  - Helicobacter pylori infection causes gastric pathology such as ulcer and
      carcinoma. Because H. pylori is auxotrophic for cholesterol, we have explored the
      assimilation of cholesterol by H. pylori in infection. Here we show that H.
      pylori follows a cholesterol gradient and extracts the lipid from plasma
      membranes of epithelial cells for subsequent glucosylation. Excessive cholesterol
      promotes phagocytosis of H. pylori by antigen-presenting cells, such as
      macrophages and dendritic cells, and enhances antigen-specific T cell responses.
      A cholesterol-rich diet during bacterial challenge leads to T cell-dependent
      reduction of the H. pylori burden in the stomach. Intrinsic alpha-glucosylation
      of cholesterol abrogates phagocytosis of H. pylori and subsequent T cell
      activation. We identify the gene hp0421 as encoding the enzyme cholesterol-alpha
      glucosyltransferase responsible for cholesterol glucosylation. Generation of
      knockout mutants lacking hp0421 corroborates the importance of cholesteryl
      glucosides for escaping phagocytosis, T cell activation and bacterial clearance
      in vivo. Thus, we propose a mechanism regulating the host-pathogen interaction
      whereby glucosylation of a lipid tips the scales towards immune evasion or
      response.

PMID- 16951685
TI  - Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by
      promoting inflammatory cell apoptosis.
AB  - Apoptosis is essential for clearance of potentially injurious inflammatory cells
      and subsequent efficient resolution of inflammation. Here we report that human
      neutrophils contain functionally active cyclin-dependent kinases (CDKs), and that
      structurally diverse CDK inhibitors induce caspase-dependent apoptosis and
      override powerful anti-apoptosis signals from survival factors such as
      granulocyte-macrophage colony-stimulating factor (GM-CSF). We show that the CDK
      inhibitor R-roscovitine (Seliciclib or CYC202) markedly enhances resolution of
      established neutrophil-dependent inflammation in carrageenan-elicited acute
      pleurisy, bleomycin-induced lung injury, and passively induced arthritis in mice.
      In the pleurisy model, the caspase inhibitor zVAD-fmk prevents R-roscovitine
      enhanced resolution of inflammation, indicating that this CDK inhibitor augments
      inflammatory cell apoptosis. We also provide evidence that R-roscovitine promotes
      apoptosis by reducing concentrations of the anti-apoptotic protein Mcl-1. Thus,
      CDK inhibitors enhance the resolution of established inflammation by promoting
      apoptosis of inflammatory cells, thereby demonstrating a hitherto unrecognized
      potential for the treatment of inflammatory disorders.

PMID- 16951686
TI  - Hematopoietic stem cell and multilineage defects generated by constitutive beta
      catenin activation.
AB  - Gain of Wnt signaling through beta-catenin has been ascribed a critical function
      in the stimulation of hematopoietic stem cell self-renewal, whereas loss of beta
      catenin is reportedly dispensable for hematopoiesis. Here we have used
      conditional mouse genetics and transplantation assays to demonstrate that
      constitutive activation of beta-catenin blocked multilineage differentiation,
      leading to the death of mice. Blood cell depletion was accompanied by failure of
      hematopoietic stem cells to repopulate irradiated hosts and to differentiate into
      mature cells. Activation of beta-catenin enforced cell cycle entry of
      hematopoietic stem cells, thus leading to exhaustion of the long-term stem cell
      pool. Our data suggest that fine-tuned Wnt stimulation is essential for
      hematopoiesis and is thus critical for therapeutic hematopoietic stem cell
      population expansion.

PMID- 16951687
TI  - Clonal deletion of thymocytes by circulating dendritic cells homing to the
      thymus.
AB  - Dendritic cell (DC) presentation of self antigen to thymocytes is essential to
      the establishment of central tolerance. We show here that circulating DCs were
      recruited to the thymic medulla through a three-step adhesion cascade involving P
      selectin, interactions of the integrin VLA-4 with its ligand VCAM-1, and
      pertussis toxin-sensitive chemoattractant signaling. Ovalbumin-specific OT-II
      thymocytes were selectively deleted after intravenous injection of antigen-loaded
      exogenous DCs. We documented migration of endogenous DCs to the thymus in
      parabiotic mice and after painting mouse skin with fluorescein isothiocyanate.
      Antibody to VLA-4 blocked the accumulation of peripheral tissue-derived DCs in
      the thymus and also inhibited the deletion of OT-II thymocytes in mice expressing
      membrane-bound ovalbumin in cardiac myocytes. These findings identify a migratory
      route by which peripheral DCs may contribute to central tolerance.

PMID- 16951688
TI  - Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor signaling
      through direct interaction with the adaptor Pellino-1.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a potent cytokine with
      pleiotropic effects, including anti-inflammatory activity. Here we show that the
      signaling protein Smad6 bound to Pellino-1, an adaptor protein of mammalian
      interleukin 1 receptor (IL-1R)-associated kinase 1 (IRAK1), and thereby promoted
      TGF-beta-mediated anti-inflammatory effects. Smad6-Pellino-1 interaction
      abrogated signaling mediated by a complex of IRAK1, Pellino-1 and adaptor protein
      TRAF6 that formed after stimulation by IL-1beta treatment. Blockade of IRAK1
      Pellino-1-TRAF6 signaling prevented degradation of the inhibitor IkappaBalpha and
      subsequent nuclear translocation of transcription factor NF-kappaB and thus
      expression of proinflammatory genes. 'Knockdown' of endogenous Smad6 expression
      by RNA interference reduced anti-inflammatory activity mediated by TGF-beta1 or
      the TGF-beta family member BMP-4. Thus Smad6 is a critical mediator of the TGF
      beta-BMP pathway that mediates anti-inflammatory activity and negatively
      regulates IL-1R-Toll-like receptor signals.

PMID- 16951689
TI  - Activation of the canonical Wnt pathway leads to loss of hematopoietic stem cell
      repopulation and multilineage differentiation block.
AB  - Wnt signaling increases hematopoietic stem cell self-renewal and is activated in
      both myeloid and lymphoid malignancies, indicating involvement in both normal and
      malignant hematopoiesis. We report here activated canonical Wnt signaling in the
      hematopoietic system through conditional expression of a stable form of beta
      catenin. This enforced expression led to hematopoietic failure associated with
      loss of myeloid lineage commitment at the granulocyte-macrophage progenitor
      stage; blocked erythrocyte differentiation; disruption of lymphoid development;
      and loss of repopulating stem cell activity. Loss of hematopoietic stem cell
      function was associated with decreased expression of Cdkn1a (encoding the cell
      cycle inhibitor p21(cdk)), Sfpi1, Hoxb4 and Bmi1 (encoding the transcription
      factors PU.1, HoxB4 and Bmi-1, respectively) and altered integrin expression in
      Lin(-)Sca-1(+)c-Kit(+) cells, whereas PU.1 was upregulated in erythroid
      progenitors. Constitutive activation of canonical Wnt signaling therefore causes
      multilineage differentiation block and compromised hematopoietic stem cell
      maintenance.

PMID- 16951690
TI  - A randomized study comparing filgrastim versus lenograstim versus molgramostim
      plus chemotherapy for peripheral blood progenitor cell mobilization.
AB  - We conducted a prospective randomized clinical trial to assess the mobilizing
      efficacy of filgrastim, lenograstim and molgramostim following a disease-specific
      chemotherapy regimen. Mobilization consisted of high-dose cyclophosphamide in 45
      cases (44%), and cisplatin/ifosfamide/etoposide or vinblastine in 22 (21%),
      followed by randomization to either filgrastim or lenograstim or molgramostim at
      5 microg/kg/day. One hundred and three patients were randomized, and 82 (79%)
      performed apheresis. Forty-four (43%) patients were chemonaive, whereas 59 (57%)
      were pretreated. A median number of one apheresis per patient (range, 1-3) was
      performed. The median number of CD34+ cells obtained after mobilization was 8.4 x
      10(6)/kg in the filgrastim arm versus 5.8 x 10(6)/kg in the lenograstim arm
      versus 4.0 x 10(6)/kg in the molgramostim arm (P=0.1). A statistically
      significant difference was observed for the median number of days of growth
      factor administration in favor of lenograstim (12 days) versus filgrastim (13
      days) and molgramostim (14 days) (P<0.0001) and for the subgroup of chemonaive
      patients (12 days) versus pretreated patients (14 days) (P<0.001). In conclusion,
      all three growth factors were efficacious in mobilizing peripheral blood
      progenitor cells with no statistically significant difference between CD34+ cell
      yield and the different regimens, and the time to apheresis is likely confounded
      by the different mobilization regimens.

PMID- 16951691
TI  - High-dose chemotherapy with autologous stem cell transplantation as first-line
      therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter
      phase II study of the GOELAMS group.
AB  - The optimum treatment of primary CNS lymphoma (PCNSL) is not yet determined. The
      objective of this study was to assess the safety and efficacy of initial
      methotrexate-based chemotherapy followed by high-dose chemotherapy (HDT) with
      autologous stem cell transplantation (ASCT) in patients with newly diagnosed
      PCNSL. Twenty-five patients received two courses of initial chemotherapy
      combining methotrexate, etoposide, carmustine and methylprednisolone, and one
      course of ifosfamide-cytarabine followed by peripheral stem cell collection.
      Seventeen responsive patients then received HDT using carmustine, etoposide,
      cytarabine and melphalan with autologous stem cell rescue. After ASCT for
      responding patients or after salvage therapy for non-responders, whole brain
      radiation therapy at a dose of 30 Gy was delivered. The objective response rate
      to the induction chemotherapy was 84%. Four of the 21 responding patients did not
      have ASCT because of toxicity or refusal. With a median follow-up time of 34
      months, the projected event free survival rate is 46% at 4 years. Projected
      overall survival is 64% at 4 years. Sixteen patients are actually in continuous
      complete response. No evidence of late treatment-related toxicity was observed.
      This treatment approach appears feasible in newly diagnosed PCNSL with
      encouraging results.

PMID- 16951692
TI  - Replacement of calcineurin inhibitors with daclizumab in patients with
      transplantation-associated microangiopathy or renal insufficiency associated with
      graft-versus-host disease.
AB  - Transplantation-associated microangiopathy (TAM) or renal insufficiency (RI)
      after allogeneic hematopoietic stem cell transplantation is associated with a
      high mortality. As calcineurin inhibitors (CI) may contribute to TAM or RI, we
      evaluated the efficacy of replacing CI by daclizumab in patients with graft
      versus-host disease (GVHD). Thirteen patients with GVHD-associated TAM and five
      patients with RI were treated with daclizumab 1 mg/kg intravenous (i.v.)/week,
      discontinuation of the CI and continuation of the remaining GVHD treatment. All
      patients had acute GVHD (steroid-sensitive (n=4), steroid-refractory (n=10)) or
      chronic GVHD (n=4) and were treated with CI before the start of daclizumab. Nine
      of 13 patients with TAM treated with daclizumab and discontinuation of CI
      achieved complete remission of TAM, two had stable disease, and one patient did
      not respond. Patients receiving daclizumab for RI without TAM showed
      stabilization (2/5) or improvement (3/5) of renal function. Four of 14 patients
      with acute GVHD achieved CR, two partial remission, eight patients did not
      respond and 11/14 died at a median of 39 days after start of the daclizumab. Our
      data demonstrate that replacement of CI by daclizumab can improve TAM and RI.
      However, mortality remains high in patients with acute GVHD.

PMID- 16951693
TI  - Effect of hematopoietic growth factors on severity of experimental autoimmune
      encephalomyelitis.
AB  - We have investigated the influence of different hematopoietic growth factors,
      including granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF),
      Flt-3 ligand (Flt-3L) and thrombopoietin (TPO), on the course of relapsing
      experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis.
      Disease course and central nervous system histology were evaluated in all groups.
      When given after immunization but before either disease onset or during
      remission, Flt-3L, SCF and G-CSF exacerbated disease severity whereas TPO had no
      effect compared to non-cytokine-treated controls. When compared to controls, TPO
      did not exacerbate disease. We conclude that autoimmune disease severity may be
      affected by hematopoietic growth factors currently being employed in
      hematopoietic stem cell transplantation of patients with autoimmune disease. The
      mechanism of their effects remains unknown: it may be related to both T helper
      (Th) 1/Th2 skewing and/or homing of inflammatory cells to the disease-affected
      organ.

PMID- 16951695
TI  - Patient-centered outcomes: a bridge too far?

PMID- 16951694
TI  - Prolonged remission in a case of Richter's transformation of B-cell chronic
      lymphocytic leukaemia following adoptive immunotherapy.

PMID- 16951696
TI  - Mode of action of hydroxychloroquine in RA-evidence of an inhibitory effect on
      toll-like receptor signaling.

PMID- 16951697
TI  - Comparison of treatment-response criteria for juvenile idiopathic arthritis.

PMID- 16951698
TI  - Ten key recommendations for the management of ankylosing spondylitis.

PMID- 16951699
TI  - Alefacept plus methotrexate for psoriatic arthritis.

PMID- 16951701
TI  - Is MRI the best method to detect response to treatment in patients with
      ankylosing spondylitis?

PMID- 16951700
TI  - Alternatives to methotrexate for infliximab combination therapy in rheumatoid
      arthritis.

PMID- 16951702
TI  - Screening for frailty among seniors in clinical practice.
AB  - The normal course of aging is associated with gradual declines in a number of
      functional abilities. Patients who are at high risk of functional decline are
      described as frail or vulnerable. A screening tool to identify such patients is
      needed, as it has been shown that intervention can delay the onset and/or slow
      the progression of functional decline. This Review describes the methods
      currently available for nonspecialist evaluation of aging individuals, including
      behavioral, interview and questionnaire assessments. Such assessments can be
      undertaken during routine physician visits. In recognition of the time pressures
      on physicians, this article focuses on those measurements that are fairly
      comprehensive yet concise, easy to administer in an office setting, and available
      in English.

PMID- 16951703
TI  - Autoimmunity to protective molecules: is it the perpetuum mobile (vicious cycle)
      of autoimmune rheumatic diseases?
AB  - Apoptotic defects and impaired clearance of cellular debris are considered key
      events in the development of autoimmunity, as they can contribute to autoantigen
      overload and might be involved in the initiation of an autoimmune response. The
      C1q protein and mannose-binding lectin are activators of the complement system.
      The pentraxins are a group of highly conserved proteins including the short
      pentraxins, C-reactive protein and serum amyloid P, and the long pentraxin family
      member, pentraxin 3, all of which are involved in innate immunity and in acute
      phase responses. In addition to their role in innate immunity and inflammation,
      each of these proteins participates in the removal of damaged and apoptotic
      cells. In this article, we discuss the clinical significance of different levels
      of these proteins, their role in the induction of or protection against
      autoimmunity, and the presence of specific autoantibodies against them in various
      autoimmune diseases.

PMID- 16951704
TI  - Does our current understanding of the molecular basis of immune tolerance predict
      new therapies for autoimmune disease?
AB  - The creation of specific immune tolerance has often been referred to as the
      ultimate goal of immunotherapy, because it would allow autoimmune disease to be
      reversed without the need for nonspecific and potentially harmful
      immunosuppressive therapy. Studies performed during the past decade have been
      immensely fruitful in terms of advances in our understanding of the cellular and
      molecular mechanisms of immune tolerance, and have paved the way for successful
      exploitation of these mechanisms for therapeutic purposes. Important developments
      include an increased understanding of central and peripheral tolerance, and
      treatment strategies that mimic the mechanisms behind deletion of self-reactive
      cells, the identification of crucial gene products that are involved in the
      induction of anergy, and the characterization of regulatory T cells and protocols
      for their induction and expansion for therapeutic applications. These landmarks
      of immune-tolerance research are summarized and their potential use in the
      immunotherapy of autoimmune disease discussed.

PMID- 16951705
TI  - Granulocyte colony-stimulating factor and neutrophils--forgotten mediators of
      inflammatory disease.
AB  - Recent studies have highlighted the functional capacity of neutrophils as
      powerful mediators of tissue inflammation. Granule-packaged proteases and
      reactive oxygen intermediates, which are important for intracellular digestion
      during phagocytosis, are released from neutrophils during inflammation. In the
      extracellular environment, neutrophil-derived proteases can cause local tissue
      damage, but also regulate the activity of cytokines, cytokine receptors and
      chemokines. Neutrophils can themselves produce an array of inflammatory
      mediators, including cytokines, chemokines and complement; these cells also
      express Fc receptors, which can bind and possibly transport immune complexes into
      the extravascular compartment, as well as activating neutrophils at opsonised
      surfaces. Blood-borne neutrophils interact with, and then exit through, the
      endothelium of blood vessels, after which these cells die and must be removed
      safely. The balance between neutrophil survival and clearance is crucial to the
      resolution of inflammation. A major regulator of neutrophil production and
      survival is the cytokine granulocyte colony-stimulating factor (G-CSF). Treatment
      with G-CSF can exacerbate underlying inflammatory diseases in humans and mice,
      and G-CSF deficiency is profoundly protective against collagen-induced arthritis
      in mice. These findings implicate G-CSF as an important proinflammatory cytokine.
      This article discusses the roles of neutrophils and G-CSF during chronic
      inflammatory diseases.

PMID- 16951706
TI  - A case of destructive Wegener's granulomatosis complicated by cytomegalovirus
      infection.
AB  - BACKGROUND: A 63-year-old man with a 4-year history of Wegener's granulomatosis
      presented with hemoptysis, palatal ulceration and sensorimotor polyneuropathy.
      INVESTIGATIONS: Physical examination, serologic testing, proteinase 3 enzyme
      linked immunosorbent assay, IgG and IgM specific to Epstein-Barr virus enzyme
      linked immunosorbent assay, MRI of the middle face, an ear, nose and throat
      consultation, immunohistochemical staining of an esophageal sample obtained from
      esophagogastroduodenoscopy, polymerase chain reaction of cytomegalovirus (CMV)
      DNA from esophageal and blood samples, and measurement of pp65 early antigen.
      DIAGNOSIS: Wegener's granulomatosis with progressive palatal ulceration and
      osseous destruction complicated by CMV-related esophagitis during induction
      treatment. MANAGEMENT: Induction treatment with cyclophosphamide pulse therapy
      was discontinued and antiviral therapy with ganciclovir was started.
      Cyclophosphamide pulse therapy was later reintroduced, but there was subsequent
      CMV reactivation, and, therefore, cyclophosphamide pulse therapy was suspended
      again and ganciclovir and intravenous immunoglobulin were started. After control
      of CMV, cyclophosphamide pulse therapy was reinitiated. Prolonged
      immunosuppressive therapy controlled disease activity, without CMV reactivation.

PMID- 16951707
TI  - Convenient syntheses of [20,20,20-H(3)]-arachidonic acid and [20,20-H(2)]-20
      hydroxyeicosatetraenoic acid.
AB  - Deuterated arachidonic acid and 20-HETE were prepared in good overall yields and
      high stereoselectivities. Key transformations include a trans-specific vinyl
      dibromide reduction and Suzuki cross-couplings to a lithium borate or a 9-BBN
      borane. These standards are three and two mass units higher, respectively, than
      their naturally occurring counterparts and are useful in mass spectrometry
      analysis.

PMID- 16951708
TI  - The Same Old Song?-Stability and Change in Relationship Schemas From Adolescence
      to Young Adulthood.
AB  - Relationship schemas are core elements of personality that guide interpersonal
      functioning. The aim of this study is to examine stability and change in
      relationship schemas across two developmental epochs-adolescence and young
      adulthood-in the stories that people tell about their interactions with others.
      Using the Core Conflictual Relationship Theme Method, relationship themes were
      coded from semistructured interviews conducted in adolescence and again at age
      25. The sample consisted of 40 participants in a longitudinal study of adolescent
      and young adult psychological development. There was considerable stability in
      the frequency with which particular themes were expressed in the narratives of
      adolescents and young adults. Significant changes from adolescence to young
      adulthood included a decrease in the perception of others as rejecting and of the
      self as opposing others. Young adults saw themselves and others more positively,
      and used a broader repertoire of themes in their relationship narratives than
      they had as adolescents. The basic continuity and particular changes in
      relationship schemas found in this study are consistent with knowledge about the
      adolescent-to-young-adult transition derived from other empirical and clinical
      findings. Relationship schemas may be rich units of study for learning about the
      development of interpersonal functioning.

PMID- 16951710
TI  - Phytochemical medicinal agents. A quinone-based route to pterocarpins.
AB  - The synthesis of 6,9 di-demethoxy kushecarpin A has been achieved by the coupling
      of a benzofuran anion with a quinone monoketal followed by a regioselective
      cyclization and a stereoselective hydrogenation reaction.

PMID- 16951709
TI  - Markers of Resilience and Risk: Adult Lives in a Vulnerable Population.
AB  - In this report, we drew on data from an ongoing longitudinal study that began in
      1978 (Hauser, Powers, Noam, Jacobson, Weiss, & Folansbee, 1984). Focusing on
      late, young-adult life among individuals who were psychiatrically hospitalized
      during adolescence, we examined markers of resilience empirically defined in
      terms of adult success and well-being. The study includes a demographically
      similar group recruited from a public high school. Major goals were to (a)
      develop preliminary models of adaptive functioning among adults in their 30s, (b)
      examine the extent to which adults with histories of serious mental disorders can
      be characterized by these models, and (c) explore predictors of successful adult
      lives from indicators of individuals' psychosocial adjustment at age 25.Results
      showed significant cohort effects on indexes of adaptive functioning, especially
      for men. Findings suggest that social relations as well as self-views of
      competence and relatedness play important roles in characterizing adjustment
      during the adult years. In addition, indexes of psychosocial adjustment as well
      as symptoms of psychiatric distress and hard drug use at age 25 made a difference
      in adult social functioning and well-being, providing hints of possible
      mechanisms likely to facilitate the ability to "bounce back" after a difficult
      adolescence.

PMID- 16951712
TI  - Regional Strength in CAM.

PMID- 16951713
TI  - Immunology and homeopathy. 4. Clinical studies-part 1.
AB  - The evidence-based research of the effectiveness of homeopathic medicines in
      common immunologic disorders is reviewed. In part 1, we introduce methodological
      issues of clinical research in homeopathy, and criteria utilized to evaluate the
      literature. Then 24 studies (12 randomized and 12 non-randomized) on common upper
      respiratory tract infections and otorhinolaryngologic complaints are described.
      In part 2, the focus will be on allergic diseases and the effectiveness of
      homeopathy will be globally evaluated and discussed using the criteria of
      evidence-based medicine.

PMID- 16951714
TI  - Maggot therapy: the science and implication for CAM part II-maggots combat
      infection.
AB  - Maggot therapy employs the use of freshly emerged, sterile larvae of the common
      green-bottle fly, Phaenicia (Lucilia) sericata, and is a form of artificially
      induced myiasis in a controlled clinical situation. Maggot therapy has the
      following three core beneficial effects on a wound: debridement, disinfection and
      enhanced healing. In part II of this review article, we discuss clinical
      infections and the evidence supporting the potent antibacterial action of maggot
      secretions. Enhancement of wound healing by maggots is discussed along with the
      future of this highly successful, often controversial, alternative treatment.

PMID- 16951715
TI  - Regulatory T cells, a potent immunoregulatory target for CAM researchers:
      modulating tumor immunity, autoimmunity and alloreactive immunity (III).
AB  - Regulatory T (T(reg)) cells are the major arbiter of immune responses, mediating
      actions through the suppression of inflammatory and destructive immune reactions.
      Inappropriate T(reg) cell frequency or functionality potentiates the pathogenesis
      of myriad diseases with ranging magnitudes of severity. Lack of suppressive
      capability hinders restraint on immune responses involved in autoimmunity and
      alloreactivity, while excessive suppressive capacity effectively blocks processes
      necessary for tumor destruction. Although the etiology of dysfunctional T(reg)
      cell populations is under debate, the ramifications, and their mechanisms, are
      increasingly brought to light in the medical community. Methods that compensate
      for aberrant immune regulation may not address the underlying complications;
      however, they hold promise for the alleviation of debilitating immune system
      related disorders. The dominant immunoregulatory nature of T(reg) cells, coupled
      with recent mechanistic knowledge of natural immunomodulatory compounds,
      highlights the importance of T(reg) cells to practitioners and researchers of
      complementary and alternative medicine (CAM).

PMID- 16951716
TI  - Insulin-sensitizing and anti-proliferative effects of Argania spinosa seed
      extracts.
AB  - Argania spinosa is an evergreen tree endemic of southwestern Morocco. Many
      preparations have been used in traditional Moroccan medicine for centuries to
      treat several illnesses including diabetes. However, scientific evidence
      supporting these actions is lacking. Therefore, we prepared various extracts of
      the argan fruit, namely keel, cake and argan oil extracts, which we tested in the
      HTC hepatoma cell line for their potential to affect cellular insulin responses.
      Cell viability was measured by Trypan Blue exclusion and the response to insulin
      evaluated by the activation of the extracellular regulated kinase (ERK1/2), ERK
      kinase (MEK1/2) and protein kinase B (PKB/Akt) signaling components. None of the
      extracts demonstrated significant cytotoxic activity. Certain extracts
      demonstrated a bi-phasic effect on ERK1/2 activation; low doses of the extract
      slightly increased ERK1/2 activation in response to insulin, whereas higher doses
      completely abolished the response. In contrast, none of the extracts had any
      significant effect on MEK whereas only a cake saponin subfraction enhanced
      insulin-induced PKB/Akt activation. The specific action of argan oil extracts on
      ERK1/2 activation made us consider an anti-proliferative action. We have thus
      tested other transformed cell lines (HT-1080 and MSV-MDCK-INV cells) and found
      similar results. Inhibition of ERK1/2 activation was also associated with
      decreased DNA synthesis as evidenced by [(3)H]thymidine incorporation
      experiments. These results suggest that the products of Argania spinosa may
      provide a new therapeutic avenue against proliferative diseases.

PMID- 16951717
TI  - Aqueous extracts of Teucrium polium possess remarkable antioxidant activity in
      vitro.
AB  - Teucrium polium L. (Lamiaceae) (RDC 1117) is a medicinal plant whose species have
      been used for over 2000 years in traditional medicine due to its diuretic,
      diaphoretic, tonic, antipyretic, antispasmodic and cholagogic properties. The
      therapeutic benefit of medicinal plants is often attributed to their antioxidant
      properties. We previously reported that an aqueous extract of the leaves and
      stems of this plant could inhibit iron-induced lipid peroxidation in rat liver
      homogenate at concentrations that were not toxic to cultured hepatic cells.
      Others have reported that organic extracts of the aerial components of this plant
      could inhibit oxidative processes. Against this background, we felt further
      investigation on the antioxidant action of the extract of T. polium prepared
      according to traditional Arab medicine was warranted. Accordingly, we assessed
      (i) its ability to inhibit (a) oxidation of beta-carotene, (b) 2,2'-azobis(2
      amidinopropan) dihydrochloride (AAPH)-induced plasma oxidation and (c) iron
      induced lipid peroxidation in rat liver homogenates; (ii) to scavenge the
      superoxide (O2*-) radical and the hydroxyl radical (OH(*)); (iii) its effects on
      the enzyme xanthine oxidase activity; (iv) its capacity to bind iron; and (v) its
      effect on cell glutathione (GSH) homeostasis in cultured Hep G2 cells. We found
      that the extract (i) inhibited (a) oxidation of beta-carotene, (b) AAPH-induced
      plasma oxidation (c) Fe(2+)-induced lipid peroxidation in rat liver homogenates
      (IC(50) = 7 +/- 2 mug ml(-1)); (ii) scavenged O2*-(IC(50) = 12 +/- 3 mug ml(-1))
      and OH(*) (IC(50) = 66 +/- 20 mug ml(-1)); (iii) binds iron (IC(50) = 79 +/- 17
      mug ml(-1)); and (iv) tended to increase intracellular GSH levels resulting in a
      decrease in the GSSG/GSH ratio. These results demonstrate that the extract
      prepared from the T. polium possesses antioxidant activity in vitro. Further
      investigations are needed to verify whether this antioxidant effect occurs in
      vivo.

PMID- 16951718
TI  - Royal jelly prevents osteoporosis in rats: beneficial effects in ovariectomy
      model and in bone tissue culture model.
AB  - Royal jelly (RJ) has been used worldwide for many years as medical products,
      health foods and cosmetics. Since RJ contains testosterone and has steroid
      hormone-type activities, we hypothesized that it may have beneficial effects on
      osteoporosis. We used both an ovariectomized rat model and a tissue culture
      model. Rats were divided into eight groups as follows: sham-operated (Sham),
      ovariectomized (OVX), OVX given 0.5% (w/w) raw RJ, OVX given 2.0% (w/w) RJ, OVX
      given 0.5% (w/w) protease-treated RJ (pRJ), OVX given 2.0% (w/w) pRJ, OVX given
      17beta-estradiol and OVX given its vehicle, respectively. The Ovariectomy
      decreased tibial bone mineral density (BMD) by 24%. Administration of 17beta
      estradiol to OVX rats recovered the tibial BMD decrease by 100%. Administration
      of 2.0% (w/w) RJ and 0.5-2.0% (w/w) pRJ to OVX rats recovered it by 85% or more.
      These results indicate that both RJ and pRJ are almost as effective as 17beta
      estradiol in preventing the development of bone loss induced by ovariectomy in
      rats. In tissue culture models, both RJ and pRJ increased calcium contents in
      femoral-diaphyseal and femoral-metaphyseal tissue cultures obtained from normal
      male rats. However, in a mouse marrow culture model, they neither inhibited the
      parathyroid hormone (PTH)-induced calcium loss nor affected the formation of
      osteoclast-like cells induced by PTH in mouse marrow culture system. Therefore,
      our results suggest that both RJ and pRJ may prevent osteoporosis by enhancing
      intestinal calcium absorption, but not by directly antagonizing the action of
      PTH.

PMID- 16951719
TI  - Centella asiatica (L.) leaf extract treatment during the growth spurt period
      enhances hippocampal CA3 neuronal dendritic arborization in rats.
AB  - Centella asiatica (CeA) is a creeping plant growing in damp places in India and
      other Asian countries. The leaves of CeA are used for memory enhancement in the
      Ayurvedic system of medicine, an alternative system of medicine in India. In this
      study, we have investigated the effect during the rat growth spurt period of CeA
      fresh leaf extract treatment on the dendritic morphology of hippocampal CA3
      neurons, one of the regions of the brain concerned with learning and memory.
      Neonatal rat pups (7 days old) were fed with 2, 4 or 6 ml kg(-1) body weight of
      fresh leaf extract of CeA for 2, 4 or 6 weeks. After the treatment period the
      rats were killed, their brains were removed and the hippocampal neurons were
      impregnated with silver nitrate (Golgi staining). Hippocampal CA3 neurons were
      traced using a camera lucida, and dendritic branching points (a measure of
      dendritic arborization) and intersections (a measure of dendritic length) were
      quantified. These data were compared with data for age-matched control rats. The
      results showed a significant increase in the dendritic length (intersections) and
      dendritic branching points along the length of both apical and basal dendrites in
      rats treated with 4 and 6 ml kg(-1) body weight per day of CeA for longer periods
      of time (i.e. 4 and 6 weeks). We conclude that the constituents/active principles
      present in CeA fresh leaf extract have a neuronal dendritic growth stimulating
      property; hence, the extract can be used for enhancing neuronal dendrites in
      stress and neurodegenerative and memory disorders.

PMID- 16951720
TI  - Keishibukuryogan (gui-zhi-fu-ling-wan), a Kampo formula, decreases disease
      activity and soluble vascular adhesion molecule-1 in patients with rheumatoid
      arthritis.
AB  - An increasing death rate due to cardiovascular disease in patients with
      rheumatoid arthritis (RA) has been reported. Keishibukuryogan (KBG) is a
      traditional Chinese/Japanese (Kampo) formula that has been administered to
      patients with blood stagnation, e.g. thrombotic disease and atherosclerosis. The
      objective of this study was to evaluate the efficacy of KBG on disease activity
      and endothelial dysfunction in RA patients. Sixteen RA patients were enrolled and
      administered KBG (12 g per day) for 12 weeks in addition to continuing other
      drugs. The disease activity of RA was assessed by modified disease activity
      scores for 28 joints (DAS(28)). Plasma levels of adhesion molecules, soluble E
      selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1) and
      soluble vascular cell adhesion molecule-1 (sVCAM-1) were evaluated. C-reactive
      protein (CRP), inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) and lipid
      peroxide (LPO) were also evaluated. Fourteen patients completed the study. The
      disease activity of RA, tender joint count, swollen joint count and DAS(28)
      decreased significantly. Among adhesion molecules, only sVCAM-1 decreased
      significantly. LPO also decreased significantly, whereas CRP and inflammatory
      cytokines remained unchanged. These results suggest that KBG has insufficient
      anti-inflammatory or immunomodulating effect but does have a beneficial effect on
      articular symptoms and a protective effect against endothelial dysfunction in RA
      patients.

PMID- 16951721
TI  - American ginseng stimulates insulin production and prevents apoptosis through
      regulation of uncoupling protein-2 in cultured beta cells.
AB  - American ginseng root displays the ability to achieve glucose homeostasis both
      experimentally and clinically but the unknown mechanism used by ginseng to
      achieve its therapeutic effects on diabetes limits its application. Disruption in
      the insulin secretion of pancreatic beta cells is considered the major cause of
      diabetes. A mitochondrial protein, uncoupling protein-2 (UCP-2) has been found to
      play a critical role in insulin synthesis and beta cell survival. Our preliminary
      studies found that the extracts of American ginseng inhibit UCP-2 expression
      which may contribute to the ability of ginseng protecting beta cell death and
      improving insulin synthesis. Therefore, we hypothesized that ginseng extracts
      suppress UCP-2 in the mitochondria of pancreatic beta cells, promoting insulin
      synthesis and anti-apoptosis (a programmed cell-death mechanism). To test the
      hypothesis, the serum-deprived quiescent beta cells were cultured with or without
      interleukin-1beta (IL-1beta), (200 pg ml(-1), a cytokine to induce beta cell
      apoptosis) and water extracts of American ginseng (25 mug per 5 mul administered
      to wells of 0.5 ml culture) for 24 h. We evaluated effects of ginseng on UCP-2
      expression, insulin production, anti-/pro-apoptotic factors Bcl-2/caspase-9
      expression and cellular ATP levels. We found that ginseng suppresses UCP-2, down
      regulates caspase-9 while increasing ATP and insulin production/secretion and up
      regulates Bcl-2, reducing apoptosis. These findings suggest that stimulation of
      insulin production and prevention of beta cell loss by American ginseng extracts
      can occur via the inhibition of mitochondrial UCP-2, resulting in increase in the
      ATP level and the anti-apoptotic factor Bcl-2, while down-regulation of pro
      apoptotic factor caspase-9 occurs, lowering the occurrence of apoptosis, which
      support the hypothesis.

PMID- 16951722
TI  - Evaluating effects of aromatherapy massage on sleep in children with autism: a
      pilot study.
AB  - Previous studies have found beneficial effects of aromatherapy massage for
      agitation in people with dementia, for pain relief and for poor sleep. Children
      with autism often have sleep difficulties, and it was thought that aromatherapy
      massage might enable more rapid sleep onset, less sleep disruption and longer
      sleep duration. Twelve children with autism and learning difficulties (2 girls
      and 10 boys aged between 12 years 2 months to 15 years 7 months) in a residential
      school participated in a within subjects repeated measures design: 3 nights when
      the children were given aromatherapy massage with lavender oil were compared with
      14 nights when it was not given. The children were checked every 30 min
      throughout the night to determine the time taken for the children to settle to
      sleep, the number of awakenings and the sleep duration. One boy's data were not
      analyzed owing to lengthy absence. Repeated measures analysis revealed no
      differences in any of the sleep measures between the nights when the children
      were given aromatherapy massage and nights when the children were not given
      aromatherapy massage. The results suggest that the use of aromatherapy massage
      with lavender oil has no beneficial effect on the sleep patterns of children with
      autism attending a residential school. It is possible that there are greater
      effects in the home environment or with longer-term interventions.

PMID- 16951723
TI  - Animal-Assisted Activity at A. Meyer Children's Hospital: A Pilot Study.
AB  - The authors systematically studied the introduction of animal-assisted activity
      into a children's hospital in Italy. This pilot study examined the reactions of
      children, their parents and the hospital staff and the hospital-wide infection
      rate before and after the introduction of animals. The SAM (self-assessment
      manikin), three behavioral scales, analysis of children's graphic productions, a
      parent questionnaire and a staff questionnaire were used to evaluate the
      effectiveness of the intervention. The children's participation was calculated.
      The analysis of the hospital infection rate was completed independently by the
      Hospital Infections Committee. The authors found that the presence of infections
      in the wards did not increase and the number of children at the meetings with
      pets in the wards was high (138 children). The study also found that the presence
      of animals produced some beneficial effects on children: a better perception of
      the environment and a good interaction with dogs. All parents were in favor of
      pets in the hospital, and 94% thought that this activity could benefit the child,
      as did the medical staff, although the staff needed more information about
      safety. The introduction of pets into the pediatric wards in an Italian
      children's hospital was a positive event because of the participation of
      hospitalized patients, the satisfaction expressed by both parents and medical
      staff, and the fact that the hospital infection rate did not change and no new
      infections developed after the introduction of dogs.

PMID- 16951724
TI  - Lead extraction: "drag through" technique.

PMID- 16951725
TI  - Reuse of occluded veins during permanent pacemaker lead extraction: a new
      indication for femoral lead extraction.
AB  - OBJECTIVES: This study examined the utility of a novel technique for reuse of
      thrombosed veins when extracting permanent pacemaker leads via a femoral vein
      approach. BACKGROUND: Although lead extraction permanent pacemaker using a
      femoral approach has advantages over the subclavian approach, it cannot be used
      to provide access for a new lead using currently employed techniques. This is
      important because up to 23% of patients have occluded veins after permanent
      pacemaker implantation. METHODS: The pacemaker lead to be extracted was released
      from the generator and retaining sutures at the implantation site. The lead was
      then grabbed from below using a needle-eye-snare or basket. The lead was then cut
      short and a drag through technique performed where a guide wire was pushed into
      the gap between the insulation and the coil. This guide wire was then drawn into
      the right atrium as the lead was pulled down from below. This guide wire was then
      used to introduce a sheath through which a replacement lead could be inserted.
      RESULTS: A total of 34 consecutive patients (21 male, aged 63+/-14 years, mean+/
      SD) had 57 (1.7/patient) leads extracted. Fourteen patients required implantation
      of a new system and were suitable for immediate lead replacement using the drag
      through technique. All leads were successfully extracted, with 5 partial
      successes (9.1% of leads). The drag-through technique was successful in all,
      including 4 with subclavian vein occlusion. Procedure and fluoroscopy times,
      including the time required for implantation of a new system, were 143+/-65 mins
      and 31+/-23 mins respectively. There were no complications and hospital stay was
      1.6+/-1.2 days for patients undergoing the drag-through procedure. CONCLUSION:
      The drag-through technique can be successfully used to provide access in order to
      replace pacemaker leads removed using a femoral approach.

PMID- 16951726
TI  - Tachycardiomyopathy.

PMID- 16951727
TI  - Pacing for vasovagal syncope.

PMID- 16951728
TI  - Approach to the evaluation and management of wide complex tachycardias.

PMID- 16951729
TI  - The long QT syndrome.

PMID- 16951730
TI  - Electrophysiological evaluation of Wolff-Parkinson-White syndrome.
AB  - Sudden death might complicate the follow-up of symptomatic patients with the
      Wolff-Parkinson-White syndrome (WPW) and might be the first event in patients
      with asymptomatic WPW. The risk of sudden death is increased in some clinical
      situations. Generally, the noninvasive studies are unable to predict the risk of
      sudden death correctly . The electrophysiological study is the best means to
      detect the risk of sudden death and to evaluate the nature of symptoms. Methods
      used to define the prognosis of WPW are well-defined. At first the maximal rate
      of conduction through the accessory pathway is evaluated; programmed atrial
      stimulation using 1 and 2 extrastimuli delivered at different cycle lengths is
      then used to determine the accessory pathway refractory period and to induce a
      supraventricular tachycardia. These methods should be performed in the control
      state and repeated in adrenergic situations either during exercise test or more
      simply during a perfusion of small doses of isoproterenol. The induction of an
      atrial fibrillation with rapid conduction through the accessory pathway (>
      240/min in control state, > 300/min after isoproterenol) is the sign of a form of
      WPW at risk of sudden death.

PMID- 16951731
TI  - Electromagnetic interference in implantable rhythm devices: comment.

PMID- 16951732
TI  - Neurodegeneration and aldehyde load: from concept to therapeutics.

PMID- 16951734
TI  - Reduced hippocampal volume correlates with executive dysfunctioning in major
      depression.
AB  - OBJECTIVE: Dysfunction of neuronal plasticity or remodelling seems to contribute
      to the pathopysiology of major depression and may cause the well-documented
      hippocampal changes in depression. We aimed to investigate whether reduced
      hippocampal volumes correlate with executive dysfunctioning or memory
      dysfunctioning or with depression severity. METHODS: We recruited 34 inpatients
      with a previous or current episode of major depression from the department of
      psychiatry at the Ludwig-Maximilians University of Munich, Germany. We examined
      the 34 patients and 34 healthy control subjects with structural high resolution
      MRI. We assessed cognitive functions with the Wisconsin Card Sorting Test (WCST)
      and the Rey Auditory Verbal Learning Test (RAVLT) and severity of depression with
      the Hamilton Depression Rating Scale. RESULTS: Hippocampal volumes and frontal
      lobe volumes were significantly smaller in patients, compared with healthy
      control subjects. Furthermore, lower hippocampal volumes were correlated with
      poorer performance in the WCST. No significant correlations were found between
      hippocampal volumes and RAVLT performance or severity of depression. CONCLUSIONS:
      The present findings emphasize that patients with reduced hippocampal volumes
      show more executive dysfunctions than their counterparts. Thus, the mechanisms
      resulting in reduced hippocampal volumes seem to be related to the development of
      major depression.

PMID- 16951733
TI  - The need for speed: an update on methamphetamine addiction.
AB  - The psychostimulant methamphetamine (MA) is a highly addictive drug that has
      surged in popularity over the last decade in North America. A burgeoning number
      of clandestine drug laboratories has led to dramatic increases in MA production,
      which have resulted in significant public health, legal and environmental
      problems. Current evidence indicates that exposure to MA is neurotoxic, and
      neuroimaging studies confirm that long-term use in humans may lead to extensive
      neural damage. These physiological changes are commonly associated with
      persistent forms of cognitive impairment, including deficits in attention, memory
      and executive function. In the present review, we provide a comprehensive
      description of the factors relating to MA use and the major health-related
      consequences, with an emphasis on MA-induced psychosis. It is hoped that
      increased knowledge of MA abuse will provide the basis for future treatment
      strategies.

PMID- 16951735
TI  - Effects of lithium and valproate on amphetamine-induced oxidative stress
      generation in an animal model of mania.
AB  - OBJECTIVE: Previous studies have suggested that oxidative stress may play a role
      in the pathophysiology of bipolar disorder (BD). Moreover, recent studies
      indicate that lithium and valproate exert neuroprotective effects against
      oxidative stress. We studied the effects of the mood stabilizers lithium and
      valproate on amphetamine-induced oxidative stress in an animal model of mania.
      METHODS: In the first model (reversal treatment), adult male Wistar rats received
      d-amphetamine or saline for 14 days, and between the 8th and 14th days, they were
      treated with lithium, valproate or saline. In the second model (prevention
      treatment), rats were pretreated with lithium, valproate or saline, and between
      the 8th and 14th days, they received d-amphetamine or saline. We assessed
      locomotor activity with the open-field task. We measured thiobarbituric acid
      reactive substances (TBARS) and protein carbonyl formation, as parameters of
      oxidative stress, and superoxide dismutase (SOD) and catalase (CAT), the major
      antioxidant enzymes, in the prefrontal cortex and hippocampus. RESULTS: Lithium
      and valproate reversed (reversal treatment model) and prevented (prevention
      treatment model) amphetamine-induced hyperactivity and reversed and prevented
      amphetamine-induced TBARS formation in both experiments. However, the co
      administration of lithium or valproate with amphetamine increased lipid
      peroxidation, depending on the brain region and treatment regimen. No changes in
      protein carbonyl formation were observed. SOD activity varied with different
      treatment regimens, and CAT activity increased when the index of lipid
      peroxidation was more robust. CONCLUSION: Our findings suggest that lithium and
      valproate exert protective effects against amphetamine-induced oxidative stress
      in vivo, further supporting the hypothesis that oxidative stress may be
      associated with the pathophysiology of BD.

PMID- 16951736
TI  - Fluoxetine-induced alterations in human platelet serotonin transporter
      expression: serotonin transporter polymorphism effects.
AB  - OBJECTIVE: Long-term antidepressant drug exposure may regulate its target
      molecule - the serotonin transporter (SERT). This effect could be related to an
      individual's genotype for an SERT promoter polymorphism (human serotonin
      transporter coding [5-HTTLPR]). We aimed to determine the effects of fluoxetine
      exposure on human platelet SERT levels. METHOD: We harvested platelet samples
      from 21 healthy control subjects. The platelets were maintained alive ex vivo for
      24 hours while being treated with 0.1 muM fluoxetine or vehicle. The effects on
      SERT immunoreactivity (IR) were then compared. Each individual's SERT promoter
      genotype was also determined to evaluate whether fluoxetine effects on SERT were
      related to genotype. RESULTS: Fluoxetine exposure replicably altered SERT IR
      within individuals. Both the magnitude and the direction of effect were related
      to a person's SERT genotype. People who were homozygous for the short gene (SS)
      displayed decreased SERT IR, whereas those who were homozygous for the long gene
      (LL) demonstrated increased SERT IR. A mechanistic experiment suggested that some
      individuals with the LL genotype might experience increased conversion of
      complexed SERT to primary SERT during treatment. CONCLUSIONS: These preliminary
      results suggest that antidepressant effects after longer-term use may include
      changes in SERT expression levels and that the type and degree of effect may be
      related to the 5-HTTLPR polymorphism.

PMID- 16951737
TI  - Psychopharmacology of smoking cessation in patients with mental illness.

PMID- 16951738
TI  - Nuclear and mitochondrial genome responses in HeLa cells treated with inhibitors
      of mitochondrial DNA expression.
AB  - The influence of mutations in the mitochondrial DNA (mtDNA) on the bioenergetic
      metabolism of the cell is still poorly understood. Many of the mutations in the
      mtDNA affect the expression of the mitochondrial genome. Investigations on cells
      from patients are not easy, especially as the mitochondrial DNA is heteroplasmic
      and this state is changed in culture. Moreover, the nuclear background and the
      mitochondrial haplotype may affect the behaviour of cells. Transfer of patient
      mitochondria to rho zero cell lines is also not optimal as these cells in general
      have many nuclear changes which may also affect cell behaviour. Thus, we decided
      to use inhibitors of mitochondrial genome expression, such as thiamphenicol,
      ethidium bromide and dideoxycytidine to investigate the bioenergetic metabolism
      of HeLa cells. We found that oxidative phosphorylation and glycolysis participate
      equally in ATP production in HeLa cells and that decreased activity of the
      respiratory chain leads to increased glycolysis and the reduction of cell growth.
      Insufficient ATP production in the oxidative phosphorylation process was not
      compensated by increased proliferation of the mitochondria. However, we were able
      to show that there are some mechanisms compensating limited expression of the
      mitochondrial genome within the mitochondria. Experiments with dideoxycytidine
      revealed that 10-fold decrease of the mtDNA copy number resulted in almost normal
      activity of cytochrome c oxidase. We found that mtDNA depletion is compensated
      mostly on the level of RNA metabolism in the mitochondria. Thus, our results are
      in agreement with the hypothesis that transcription initiation rather than mtDNA
      copy number is a rate limiting factor for expression of the mitochondrial genome.

PMID- 16951739
TI  - Curcumin induces cell death without oligonucleosomal DNA fragmentation in
      quiescent and proliferating human CD8+ cells.
AB  - Cytotoxic CD8+ cells play an important role in determining host response to
      tumor, thus chemotherapy is potentially dangerous as it may lead to T cells
      depletion. The purpose of this study was to elucidate the propensity of quiescent
      and proliferating human CD8+ cells to undergo cell death upon treatment with
      curcumin, a natural dye in Phase I of clinical trials as a prospective
      chemopreventive agent. METHODS: We treated human quiescent or proliferating CD8+
      cells with 50 microM curcumin or irradiated them with UVC. Cell death symptoms
      such as decreased cell viability, chromatin condensation, activation of caspase-3
      and specific DFF40/CAD endonuclease and oligonucleosomal DNA fragmentation were
      analyzed using MTT test, microscopic observation, Western blotting and flow
      cytometry. RESULTS: Curcumin decreased cell viability, activated caspase-3 and
      decreased the level of DFF45/ICAD, the inhibitor of the DFF40/CAD endonuclease.
      However, this did not lead to oligonucleosomal DNA degradation. In contrast, UVC
      irradiated proliferating, but not quiescent CD8+ cells revealed molecular and
      morphological changes characteristic for apoptosis, including oligonucleosomal
      DNA fragmentation. Curcumin can induce cell death in normal human lymphocytes
      both quiescent and proliferating, without oligonucleosomal DNA degradation which
      is considered as a main hallmark of apoptotic cell death. Taking into account the
      role of CD8+ cells in tumor response, their depletion during chemotherapy could
      be particularly undesirable.

PMID- 16951740
TI  - Melanin synthesis in microorganisms--biotechnological and medical aspects.
AB  - Melanins form a diverse group of pigments synthesized in living organisms in the
      course of hydroxylation and polymerization of organic compounds. Melanin
      production is observed in all large taxa from both Pro- and Eukaryota. The basic
      functions of melanins are still a matter of controversy and speculation, even
      though their adaptative importance has been proved. Melanogenesis has probably
      evolved parallel in various groups of free living organisms to provide protection
      from environmental stress conditions, but in pathogenic microorganisms it
      correlates with an increased virulence. The genes responsible for melanization
      are collected in some cases within operons which find a versatile application in
      genetic engineering. This review summarizes current views on melanogenesis in Pro
      and Eukaryotic microorganisms in terms of their biotechnological and biomedical
      importance.

PMID- 16951741
TI  - pH profile of cytochrome c-catalyzed tyrosine nitration.
AB  - In the present study, we investigated how cytochrome c catalyzed the nitration of
      tyrosine at various pHs. The cytochrome c-catalyzed nitration of tyrosine
      occurred in proportion to the concentration of hydrogen peroxide, nitrite or
      cytochrome c. The cytochromec-catalyzed nitration of tyrosine was inhibited by
      catalase, sodium azide, cystein, and uric acid. These results show that the
      cytochrome c-catalyzed nitrotyrosine formation was due to peroxidase activity.
      The rate constant between cytochrome c and hydrogen peroxide within the pH range
      of 3-8 was the largest at pH 6 (37 degrees C). The amount of nitrotyrosine formed
      was the greatest at pH 5. At pH 3, only cytochromec-independent nitration of
      tyrosine occurred in the presence of nitrite. At this pH, the UV as well as
      visible spectrum of cytochrome c was changed by nitrite, even in the presence of
      hydrogen peroxide, probably via the formation of a heme iron-nitric oxide
      complex. Due to this change, the peroxidase activity of cytochrome c was lost.

PMID- 16951742
TI  - Rapid and simple screening of transgenic mice: novel extraction-free, filter
      based PCR genotyping from blood samples.
AB  - We evaluated the effectiveness of using Flinders Technology Associates (FTA)
      filter paper for the polymerase chain reaction (PCR) genotyping of transgenic
      mice. Tail prick blood sample dried on an FTA filter disc was processed for
      genomic PCR. It is easy and rapid to prepare DNA templates because the protocol
      is extraction-free and only requires minimal handling of wash briefly
      bloodstained FTA filter discs. Progeny of a transgene-positive founder mated with
      wild-type mice was screened for the presence of the transgene by the filter-based
      PCR using transgene-specific primers. The resulting amplicons with expected sizes
      of 3134 bp, 1152 bp, 877 bp and 688 bp were robust and reproducible, allowing a
      distinction between transgenic (n=44) and wild-type (n=47) mice showing no
      signal. The filter-based PCR screening took only half a day. The present study
      confirmed the validity and usefulness of the novel rapid extraction-free
      genotyping method.

PMID- 16951743
TI  - Molecular cloning and functional expression of human cytosolic acetyl-CoA
      hydrolase.
AB  - A cDNA encoding human cytosolic acetyl-CoA hydrolase (CACH) was isolated from a
      human liver cDNA library, sequenced and functionally expressed in insect cells.
      The human CACH cDNA encodes a 555-amino-acid sequence that is 81.4%/78.7%
      identical to those of the mouse/rat homologue, suggesting a conserved role for
      this enzyme in the human and rodent livers. Bioinformatical study further reveals
      a high degree of similarity among the human and rodent CACHs as follows: First,
      the gene is composed of 15 exons ranging in size from 56 to 157 bp. Second, the
      protein consists of two thioesterase regions and a C-terminal steroidogenic acute
      regulatory protein-related lipid transfer (START) domain. Third, the promoter
      region is GC-rich and contains GC boxes, but lacks both TATA and CCAAT boxes, the
      typical criteria of housekeeping genes. A consensus peroxisome proliferator
      responsive element (PPRE) present in the rodent CACH promoter regions supports
      marked CACH induction in rat liver by peroxisome proliferator (PP).

PMID- 16951744
TI  - Different gene expression profiles of AD293 and HEK293 cell lines that show
      contrasting susceptibility to apoptosis induced by overexpression of Bim L.
AB  - Bim is a pro-apoptotic member of the Bcl-2 protein family. Overexpression of Bim
      proved to be highly cytotoxic for diverse cells. The AD293 cell line is derived
      directly from the HEK293 cell line but has been transfected with a gene that can
      improve cell adherence. We found that there was almost no apoptosis seen in Bim L
      transfected AD293 cells, but more than half of Bim L-transfected HEK293 cells
      underwent apoptosis. Suppression subtractive hybridization was used to detect the
      different gene expression profile between these two cell lines. In 192 sequenced
      positive clones, there were 30 clones repeating twice or more. Ten genes were
      selected for identification by semi-quantitative RT-PCR. The transcripts of two
      adhesion-related genes (actin and parvin) and two apoptosis-related genes (cyclin
      2 and protein phosphatase 1G) were up-regulated in AD293 cells. These results
      suggest that the high expression of cell adhesion-related proteins might be
      responsible for the different apoptosis status after the transfection of Bim L.
      Our data provide candidate genes responsible for the different apoptosis
      sensitivity of these two cell lines. Further investigation on the differential
      expression profile between AD293 and HEK293 might improve our understanding of
      cell apoptosis mechanism.

PMID- 16951746
TI  - Aquatic processes and systems in perspective.

PMID- 16951747
TI  - Antifouling strategies for marine and riverine sensors.
AB  - Traditionally, water quality has been monitored by sampling and lab based
      analysis. However, there are disadvantages associated with this method, for
      example, deterioration of samples with time, limited sampling points, limited
      temporal monitoring. This has provided impetus for the development of sensors
      which can be deployed from remote locations over extended deployment periods.
      However, a major limitation of these systems is their vulnerability to
      biofouling. This review outlines the research that has been carried out on
      strategies for the protection of marine and riverine sensors against fouling.

PMID- 16951748
TI  - Sediment influence on congener-specific PCB bioaccumulation by Mytilus edulis: a
      case study from an intertidal hot spot, Clyde Estuary, UK.
AB  - An intertidal site in the Clyde Estuary, UK, was selected to evaluate the role of
      sediment geochemistry on the bioaccumulation of polychlorinated biphenyls (PCBs)
      by mussels (Mytilus edulis). The area had previously been identified as showing
      anomalously high levels of PCB contamination (over 1,500 microg kg(-1) total PCB
      in sediment, 22 congeners). Samples of surface sediment and M. edulis were
      collected from two closely located sites, one within the anomalous area and
      another representing typical PCB contamination in the estuary. Sediment samples
      were separated into grain size fractions and analysed for a range of biomarker
      compounds, PCBs and sediment mineralogy. The anomalous site showed an atypical
      association of PCBs with sediment properties, despite both locations showing
      influence of both petrogenic and pyrogenic organic contamination. Interrogation
      of data using correlation and principal component analysis showed that sediment
      mineralogy as well as organic matter composition influenced PCB congener
      distribution. One sediment source was found to control the PCB concentration in
      mussels at both locations and clay mineralogy appears to control PCB uptake by
      biota with preference for higher molecular weight congeners. Overall
      bioavailability is determined by sediment TOC.

PMID- 16951749
TI  - Determination of synthetic musk compounds in sewage biosolids by gas
      chromatography/mass spectrometry.
AB  - A review of sewage sludge regulations and land application practices by the
      United States National Research Council (2002) recommended development of
      improved analytical techniques to adequately identify and quantify new chemical
      contaminants, such as synthetic musk compounds in Class A sewage sludge (i.e.,
      biosolids). This prompted the development of a rugged analytical method using gas
      chromatography coupled to mass spectrometry to detect this group of organic
      pollutants in biosolids. In this paper, the term "biosolids" is used
      interchangeably with "sewage sludge", which is defined in the regulations and
      used in the statue (Clean Water Act). Samples of Class A biosolids obtained from
      sewage treatment plants in Los Angeles, California, the City of Las Vegas,
      Nevada, and also in the form of a commercial fertilizer, were extracted using
      pressurized liquid extraction technique, subjected to gel permeation
      chromatography clean-up, and analyzed by GC/MS using the selected ion monitoring
      mode. The method developed has the potential to detect synthetic musk compounds
      in complex matrices, may provide accurate data useful in human health and
      environmental risk assessment, and may be useful in determining the efficacy of
      municipal sewage treatment plants for removing synthetic musk compounds.

PMID- 16951750
TI  - Microscopic and chemical studies of metal particulates in tree bark and attic
      dust: evidence for historical atmospheric smelter emissions, Humberside, UK.
AB  - Tree barks and attic dusts were examined as historical archives of smelter
      emissions, with the aim of elucidating the pathways of pollution associated with
      a plume of Sn and Pb contamination in top soils, found close to the former Capper
      Pass smelter, Humberside, UK. Samples were collected from three villages within
      the area of the contamination plume. Scanning electron microscopy (SEM) and bulk
      chemical analyses were used to assess particle type, number and deposition
      patterns. SEM analysis of dusts and bark revealed that Sn and Pb particles were
      present in samples from all three villages along with copper, zinc and iron
      particles. These were almost entirely <10 microm in diameter and occurred mostly
      as oxides, frequently forming clusters of sub-micron crystals. Samples further
      from the smelter contained considerably fewer particles. We present images of
      smelter derived Sn particles. Chemical assays of the barks and attic dusts
      demonstrated that concentrations of Sn, Pb, Cu, As, Sb and Cd diminished with
      increasing distance from the source. Strong positive correlations were found
      between Sn and Pb, As, Sb and Cd in the attic dusts. Enrichment factors (EF) were
      calculated for these trace elements based on topsoil element concentrations
      obtained from the soil survey of the study area. Decreases in these trace element
      concentrations and EF values with distance away from the smelter are consistent
      with trends found in the soil survey for Sn and Pb and are typical of deposition
      patterns around smelter stacks. The study demonstrates that tree bark and attic
      dusts can be effective archives of metal particulates deposited from large static
      emission sources.

PMID- 16951751
TI  - Fractionation of eleven elements by chemical bonding from airborne particulate
      matter collected in an industrial city in Argentina.
AB  - A four-step chemical sequential extraction procedure was used to evaluate the
      distribution of Al, As, Cr, Cu, Fe, Mn, Ni, Pb, Ti, V and Zn in airborne
      particulate matter collected on glass fibre filters using a high-volume sampler.
      Two sets of samples were collected in 2001 (winter and summer campaigns) in
      representative zones of an industrial city of Argentina. The leaching scheme was
      applied to PM-10 particles and consisted in extracting the elements in four
      fractions, namely soluble and exchangeable elements; carbonates, oxides and
      reducible elements; bound to organic matter and sulfidic metals; and residual
      elements. Metals and metalloids at microg g(-1) level were determined in each
      fraction by inductively coupled plasma optical emission spectrometry (ICP OES).
      Analyte concentration varied from 14 microg g(-1) (equivalent to 1.0 ng m(-3))
      for As to 11.8 mg g(-1) (equivalent to 2,089 ng m(-3)) for Al. Seven elements,
      namely Al, Cr, Fe, Mn, Pb, Ti and Zn showed similar distributions in both seasons
      while As was distributed in a significantly different manner in each season. The
      results exhibited low As contents in the first and second fractions that could be
      associated with routine coal combustion and a high content in the third and
      fourth fractions of the summer samples that could be linked to the use of
      pesticides. Aluminium, As, Cu, Mn, Ni, Ti, V and Zn were found in different
      percentages in the more bioavailable aqueous fraction with As, Mn, V and Zn
      exhibiting solubilities greater than 1% while Cr and Pb being insoluble. The
      content of Al, Cr, Cu, Fe, Ni, Pb, and Zn in the residual fraction was, in
      average, higher than 50%. A comparative assessment of the use of the underlying
      information available from fractionation studies compared to that obtained from
      total element content was done for Fe and Mn. It showed that the results obtained
      using chemical sequential extraction procedures allowed further discrimination of
      the potential air pollution sources.

PMID- 16951752
TI  - Treatment of microbiologically polluted aquaculture waters by a novel
      photochemical technique of potentially low environmental impact.
AB  - The applicability of a novel procedure for the disinfection of microbiologically
      polluted waters from fish-farming ponds, based on the combined action of visible
      light (including sunlight) and porphyrin-type photosensitising agents, has been
      investigated using (a) cell cultures of a Gram-positive bacterium (meticillin
      resistant Staphylococcus aureus), a Gram-negative bacterium (Escherichia coli)
      and a fungal pathogen (Saprolegnia spp.); (b) pilot aquaculture plants involving
      either spontaneously or artificially Saprolegnia-infected rainbow trout
      (Oncorhynchus mykiss). The results obtained by using two cationic porphyrins,
      namely a tetra-substituted N-methyl-pyridyl-porphine (C1) and its analogue where
      one N-methyl group had been replaced by a N-tetradecyl chain (C14), and low
      intensity visible light irradiation showed an extensive (up to 6-7 log) decrease
      in the bacterial/fungal population after short incubation and irradiation times
      in the presence of micromolar photosensitiser concentrations. Moreover, C14
      showed some toxic effect also in the absence of light. Extension of these studies
      to the pilot plants indicated that both C1 + light and C14 can prevent
      Saprolegnia infections or promote the cure of saprolegniasis in infected trout by
      treatments with submicromolar porphyrin doses. The procedure appears to be of low
      cost and to have a low environmental impact.

PMID- 16951753
TI  - Surface acoustic wave (SAW) microsensor array for measuring VOCs in drinking
      water.
AB  - Exposure to volatile organic chemicals (VOCs) in drinking water has been linked
      to a number of adverse health effects including cancer, liver, and kidney damage.
      However, the large number of potential contaminants and the cost and complexity
      of existing analytical methods limits the extent to which water quality is
      routinely characterized. This project focused on the laboratory development and
      evaluation of an instrument for field analysis of VOCs in drinking water. The
      instrument is based on an array of six polymer-coated surface-acoustic-wave
      microsensors. A test-set consisting of dichloromethane, chloroform, 1,1,1
      trichloroethane, perchloroethylene, and m-xylene was used in a series of
      experiments designed to optimize the purge-trap preconcentration system,
      calibrate the instrument over the concentration range of 0.2-2 times the USEPA
      maximum contaminant levels (MCLs), and compare results to those of a reference
      laboratory. The primary goal was to develop a cost-effective alternative for on
      site evaluation of VOCs in water. Calibration and evaluation test results for
      spiked water samples demonstrate adequate sensitivity for 19 of the 21 regulated
      VOCs considered using a ten minute sampling and analysis cycle. Monte Carlo
      simulations characterized the performance of trained artificial neural networks
      (ANNs) which had correct classification rates of 99%, 90%, and 80% for the five
      individual test-set vapors and their binary and ternary mixtures, respectively.
      These results demonstrate the excellent potential of this technology for
      addressing the need for improved VOC field-screening methods for water supplies.

PMID- 16951754
TI  - A rapid lateral flow immunoassay for the detection of fungal alpha-amylase at the
      workplace.
AB  - Fungal alpha-amylase is a flour supplement which is added to improve the quality
      of bakery products. Various studies have shown that exposure to this enzyme is an
      important risk factor for the development of bakers' allergy and this allergy is
      reported to be one of the most frequent causes of occupational asthma. A rapid
      assay was developed to monitor exposure to occupational allergens directly at the
      workplace. The sensitivity of the developed assay is 0.32 ng amylase mL(-1) in a
      buffer system with the commercially available alpha-amylase preparation Fungamyl
      1600S as the standard. Initial validation tests (n = 33) were performed with
      airborne and settled dust from an industrial bakery. The new lateral flow
      immunoassay detected amylase in 22 of the 26 samples regarded as positive in an
      enzyme immunoassay, and was negative for all seven enzyme immunoassay-negative
      samples, while the four lateral flow immunoassay-negative/enzyme immunoassay
      positive samples all had levels below 2 ng mL(-1). The sensitivity of 2 ng mL(-1)
      of the amylase lateral flow immunoassay is sufficient for first screening
      purposes and, therefore, this simple and rapid assay may allow direct on-site
      demonstration of work-related hazards of bio-allergen exposure. This would be
      particularly useful in occupational hygiene practice, especially in traditional
      or small-scale bakeries which lack the technological skills for testing the
      exposure to respiratory allergens.

PMID- 16951755
TI  - Near-field loading dynamics of total phosphorus and short-term water quality
      variations at a rainbow trout cage farm in Lake Huron.
AB  - Aquatic total phosphorus (Tot-P) is measured at fish-cages in Lake Huron for
      environmental regulatory compliance. An improved understanding of how Tot-P is
      manifested in the near-field (<or=30 m) water column relative to reference sites
      within the same water body, current movement and farm structures is required to
      help interpret sample results and refine monitoring protocols where necessary.
      The primary aim of this study is to investigate spatial and temporal
      concentrations of Tot-P at a commercial fish farm. A secondary aim investigates
      the utility of automated dissolved oxygen (DO) and pH monitoring to assist with
      Tot-P monitoring. Near-field TP at a commercial rainbow trout (Oncorhynchus
      mykiss) cage-farm in the North Channel of Lake Huron was intensively sampled for
      six multi-day periods of differing environmental and fish production scenarios.
      Current profiles were measured by acoustical Doppler current profilers for five
      periods, and multi-probes continuously measured temperature, pH and dissolved
      oxygen, at the farm centre and 30 m north/south for two sampling periods. Near
      field Tot-P data was non-normally distributed. Differences between parametric and
      non-parametric measures were minor. Phosphorus depth profiles appeared to be
      influenced by the locations of cages, manure collectors and the lake bottom. Near
      field lateral Tot-P concentrations were elevated above background only in down
      current locations except during one period of high production and slow current
      velocity; suggesting adequately flushed cages will have background concentrations
      at up-current locations. Variation of DO, pH and Tot-P and the correlations among
      these parameters, increased from the up-current, down-current and the site centre
      locations, respectively. These relationships suggest some limited utility for the
      use multi-probes deployed around fish cages to determine nutrient flow direction,
      thereby inferring short-term trends of Tot-P concentrations adjacent to the farm.
      Implications for present monitoring practices are discussed.

PMID- 16951756
TI  - Estimating sampling frequency in pollen exposure assessment over time.
AB  - A time series model was fitted to the pollen concentration data collected in the
      Greater Cincinnati area for the Cincinnati Childhood Allergy and Air Pollution
      Study (CCAAPS). A traditional time series analysis and temporal variogram
      approach were applied to the regularly spaced databases (collected in 2003) and
      irregularly spaced ones (collected in 2002), respectively. The aim was to
      evaluate the effect of the sampling frequency on the sampling precision in terms
      of inverse of standard error of the overall level of mean value across time. The
      presence of high autocorrelation in the data was confirmed and indicated some
      degree of temporal redundancy in the pollen concentration data. Therefore, it was
      suggested that sampling frequency could be reduced from once a day to once every
      several days without a major loss of sampling precision of the overall mean over
      time. Considering the trade-offs between sampling frequency and the possibility
      of sampling bias increasing with larger sampling interval, we recommend that the
      sampling interval should take values from 3 to 5 days for the pollen monitoring
      program, if the goal is to track the long-term average.

PMID- 16951757
TI  - Earthworm cytochrome P450 determination and application as a biomarker for
      diagnosing PAH exposure.
AB  - We developed a new microsome purification method and used the Omura and Sato
      method to measure the total content of cytochrome (Cyt) P450 in earthworm
      (Eisenia fetida) microsomes. In method development, two different pretreatments,
      i.e. solubilization or manual separation were used to purify worm microsomes.
      Solubilization was more effective than manual separation and difference spectra
      showed a peak at 450 +/- 1 nm in microsomes received solubilization pretreatment.
      We conducted a 48 h contact test by exposing worms on pyrene (Py) and
      benzo[a]pyrene (BaP) spiked filter paper. A dose-response relationship was
      established between total P450 content and the concentration of Py or BaP ranging
      from 10(-6) mg mL(-1) to 10(-2) mg mL(-1). Results show that total Cyt P450
      content in earthworms is a promising biomarker for diagnosing PAHs exposure at
      sublethal dose ranges.

PMID- 16951758
TI  - Investigation of sequential and enzymatic extraction of arsenic from drinking
      water distribution solids using ICP-MS.
AB  - A sequential extraction approach was utilized to estimate the distribution of
      arsenite [As(iii)] and arsenate [As(v)] on iron oxide/hydroxide solids obtained
      from drinking water distribution systems. The arsenic (As) associated with these
      solids can be segregated into three operationally defined categories
      (exchangeable, amorphous and crystalline) according to the sequential extraction
      literature. The exchangeable As, for the six drinking water solids evaluated, was
      estimated using 10 mM MgCl(2) and 10 mM NaH(2)PO(4) and represented between 5-34%
      of the total As available from the solid. The amorphously bound As was estimated
      using 10 mM (NH(4))(2)C(2)O(4) and represented between 57-124% of the As
      available from the respective solid. Finally, the crystalline bound As was
      estimated using titanium citrate and this represented less than 1.5% of the As
      associated with the solids. A synthetic stomach/intestine extraction approach was
      also applied to the distribution solids. The stomach fluid was found to extract
      between 0.5-33.3 microg g(-1) As and 120-2,360 microg g(-1) iron (Fe). The As
      concentrations in the intestine fluid were between 0.02-0.04 microg g(-1) while
      the Fe concentration ranged from 0.06-0.7 microg g(-1) for the first six drinking
      water distribution solids. The elevated Fe levels associated with the stomach
      fluid were found to produce Fe based precipitates when the intestinal treatment
      was applied. Preliminary observations indicate that most of the aqueous Fe in the
      stomach fluid is ferric ion and the observed precipitate produced in the
      intestine fluid is consistent with the decreased solubility of ferric ion at the
      pH associated with the intestine.

PMID- 16951759
TI  - Clinical quiz. Exertional dyspnea in a 50-year-old man.

PMID- 16951760
TI  - Pre-marital examination as a method of prevention from blood genetic disorders.
      Community views.
AB  - The Saudi Royal Cabinet issued the Saudi Royal Decree No. 3 dated 11-7-1424,
      establishing the pre-marital examination as a health preventive measure for all
      Saudis, and requesting the 2 prospective partners (male and female) to carry out
      a pre-marital examination and present a certificate of pre-marital examination
      before the wedding. However, the prospective husband and wife are not obliged to
      abide by the laboratory results if they so wish. This program started officially
      on the 1st of Muharram, 1425. As a consequence, the community perception and
      views on the pre-marital examination program as a preventive measure become
      crucial. Therefore, this study was organized and conducted to reveal the
      perception of the community regarding the program, through a purpose-made
      questionnaire that was distributed during symposia and awareness lectures held
      throughout the Kingdom (Riyadh, Jeddah, Dammam, Al-Khobar, Al-Ahsa, Al-Qassim,
      and Madinah). The questionnaire covers the opinions of the participants in
      various aspects related to genetic diseases including nature of diseases, mode of
      transmission, affecting factors, complications, management, and prevention. In
      addition, the questionnaire also covers opinions regarding the pre-marital
      examination as a preventive measure of blood genetic diseases, and its
      contribution to the control of these diseases. The questionnaire also covers
      methods in obtaining information, whether from studies, lectures, information
      media, and awareness lectures. The results revealed that the majority of the
      participants (94.3%) were convinced that the pre-marital examination is an
      effective mean of prevention of blood genetic diseases. The majority (86.9%) of
      the participants were also convinced that the pre-marital examination should be
      mandatory. These are indications that the community is aware of the pre-marital
      examination, and the effectiveness of the awareness program is enriching the
      knowledge of the citizens.

PMID- 16951761
TI  - A Cochrane Systematic Review finds no significant difference in outcome or risk
      of postoperative complications between day care and in-patient cataract surgery.
AB  - This review was conducted to determine reliable evidence regarding the safety,
      feasibility, effectiveness, and cost-effectiveness of cataract extraction
      performed as a day care versus in-patient procedure. The search to identify
      randomized controlled trials comparing day care and in-patient surgery for age
      related cataract included the Cochrane Eyes and Vision Group Trials Register, the
      Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and LILACS Latin
      American and Caribbean Literature on Health Sciences. Assessment of
      methodological quality was based on criteria defined by the Cochrane
      Collaboration. The primary outcome was the achievement of a satisfactory visual
      acuity 6 weeks after operation. Two trials, involving a total of 1284 people, are
      included. One trial reported statistically significant differences in early
      postoperative complication rates in the day care group, which had no clinical
      relevance to visual outcomes 4 months postoperatively. Mean change in visual
      acuity Snellen lines of the operated eye 4 months postoperatively was 4.1
      standard deviation SD 2.3 for the day care group and 4.1 SD 2.2 for the in
      patient group. Costs were 20% more for the in-patient group attributable to
      higher costs for overnight stay.

PMID- 16951762
TI  - The role of heat shock proteins as chaperones on several human diseases.
AB  - Some heat shock proteins HSPs, act as molecular chaperones. These and other
      molecular chaperones that are not HSPs, function in a variety of protein
      biosynthetic event and protect proteins from the deleterious effects of stressors
      by stabilizing, and refolding proteins. They assist protein folding, assembly,
      transport and degradation. Several human diseases such as neurodegeneration,
      cancer, aging, retinal dystrophy, and inflammation arise from defects HSPs and
      protein folding. This review demonstrates the chaperones such as properties of
      HSPs in cellular processes and their implication in different kind of human
      diseases.

PMID- 16951763
TI  - On the Ottoman consent documents for medical interventions and the modern concept
      of informed consent.
AB  - Information for patients prior to medical intervention is one of the principles
      of modern medical practice. In this study, we looked at an earlier practice of
      this principle. Ottoman judges had record books called sicil. One of the
      categories in sicils was the consent documents called riza senedi, which was a
      patient-physician contract approved by the courts. These contracts were
      especially for the protection of physicians from punishment if the patient dies.
      It is not clear whether patients were informed properly or not. Consent for
      minors was obtained from parents. However, a situation where an adult does not
      have the capacity to consent, was not clear in these documents. Any sign of free
      withdrawal of consent was not found in these records. Due to the legal system of
      Ottoman State, these contracts were related to Islamic law rather than modern
      civil law. We aim, in this paper, to present a legal practice, which is possible
      to consider as an early example of the informed consent practice.

PMID- 16951764
TI  - Development of fetal rat pancreatic islet A cells. A quantitative and
      immunocytochemical study.
AB  - OBJECTIVE: To perform a detailed quantitative immunocytochemical study of the
      development of fetal rat pancreatic islet A cells. METHODS: Pancreases were
      obtained from 19 and 21-day- old fetal rats. Ten rats were used per each group.
      Non-fasting blood glucose levels were measured to confirm that the animals were
      normoglycemic. The pregnant rats were anesthetized by ether inhalation, and the
      fetuses were removed from their uteruses. They were fixed in buffered neutral
      formalin, dehydrated and embedded in paraplast and serially sectioned (5 microm).
      We examined 32-48 islets (8-12 per section) for each fetus. Sections were stained
      by avidin biotin complex technique. A quantitative study was performed on the
      pancreatic islet A cells. Carl Zeiss software from Zeiss was used in this study.
      This study was carried out at the Department of Anatomy, King Abdul-Aziz
      University, Jeddah, Kingdom of Saudi Arabia during the period January to December
      2005. RESULTS: The volume density and the number of A cells showed a significant
      increase during the last days of gestation. All other parameters showed a
      significant increase during the last days of gestation. The A cell nuclear
      diameter and volume did not increase significantly during the last days of
      pregnancy. The A cells were well stained and occupied the peripheral part of the
      islets. CONCLUSION: The present study represented a detailed quantitative
      immunohistochemical study and demonstrated that the size of the endocrine tissue
      and the islet A cells increased significantly during the last days of gestation.

PMID- 16951765
TI  - The proportions of the white and red pulps of the human fetal spleen.
AB  - OBJECTIVE: To compare the proportions of white and red pulps of the human spleen
      during the fetal period. METHODS: We performed this study in the Department of
      Anatomy and Pathology of Suleyman Demirel University, Faculty of Medicine,
      Isparta, Turkey, from the period between 2002-2003. Spleens from 137 dead fetuses
      aged between 9 and 40 weeks were embedded into paraffin blocks following
      classical histological steps and stained with hematoxylin and eosin. White and
      red pulps could be differentiated only in 25 cases (13 males, 12 females). The
      proportions of the areas of white and red pulps (the trabeculae were included
      into the red pulp and the groups of lymphocytes were included into the white
      pulp) were estimated by point counting method on the sections taken from
      different parts of the spleens by systematic randomized sampling technique.
      RESULTS: It has been ascertained that the white pulp has been distinguished from
      20th week onwards during the fetal period. The proportion of the white pulp area
      has been found to be 22.3% (of total white and red pulp areas) at the 20th week
      and has come to 37.6% at the 40th week. Concerning the trimesters, the proportion
      of the white pulp area has been found to be 30% (of total white and red pulp
      areas) at the 2nd trimester and has come to 36% at full term. While the white
      pulp area had a positive correlation with the gestational age (r: 0.34), the red
      pulp area had a negative one (r: -0.34). No difference has been found among
      gender. CONCLUSION: Reference values have been obtained about the proportions of
      white and red pulp areas of human fetal spleen.

PMID- 16951766
TI  - Anatomical basics and variations of the scapula in Turkish adults.
AB  - OBJECTIVE: To analyze the anatomical basis of the scapula, acromion, os
      acromiale, coracoid process, coraco-acromial arch, and glenoid cavity in Turkish
      adults. METHODS: We performed the study at the Faculty of Medicine, Akdeniz
      University, Turkey between January 2004 and December 2005. A total of 90 dry
      bones of the scapula from human cadavers were randomly selected. The length,
      width, and anterior thickness of the acromion and the acromial facet of the
      acromioclavicular joint were measured with an electronic caliber and was examined
      visually. For the radiological evaluation, the posterior anterior and the lateral
      shoulder radiographs of 90 consecutive adult patients with normal findings were
      used. These films were evaluated and grouped according to the acromial arch
      morphology. RESULTS: The distribution of the acromial morphologic types according
      to slope was type I (flat) 10%, type II (curved) 73%, type III (hooked) 17%. Type
      I was seen in 11%, type II 66%, type III 23% of the specimens. The morphological
      shape of the tip of the acromion was 31% cobra shaped, 13% square shaped, and 56%
      intermediate type. The scapulas, coracoid process and the coraco acromial arch
      were measured. In 72% of the specimen, the glenoid notch of the scapulas were
      absent and oval shaped, whereas in 28% the notch was well expressed and the
      glenoid cavity was pear shaped. The mean vertical length of the glenoid cavity
      was 36.3 +/- 3 mm, and the mean transverse length was 24.6 +/- 2.5 mm. Os
      acromiale is a rare anatomical condition. Its incidence has been documented in
      radiographic and anatomical studies to be between 1-15%. The presence of os
      acromiale was 1% in shoulder radiographs (os pre-acromiale), and in dry bones (os
      meta-acromiale) CONCLUSION: We reported the exact morphological measurements of
      the bone structures of the scapula in Turkish adult population. Our results
      present an instructive figures of anatomical preparations and radiological cases
      that can be used to make a more precise radiological and a differential
      diagnoses.

PMID- 16951767
TI  - Computed tomography in detecting bone metastases of breast carcinoma. Is it
      better than plain x-ray?
AB  - OBJECTIVE: To compare 5mm slice computerized tomography (CT) and conventional x
      ray (XR) in the detection of bone metastases in breast carcinoma patients.
      METHODS: Ninety-eight female breast cancer patients treated in Ankara Oncology
      Hospital, Ankara, Turkey between September 1997 and March 2002 were assigned into
      3 groups with respect to their Tc bone scan (Sc) results. Group 1 included
      patients with overt bone metastases, group 2 included patients with suspicious of
      metastases and group 3 were those patients with normal Sc results with back pain
      complaint. All patients underwent XR, and 5mm contiguous slice CT imaging for the
      related metastatic sites. For the third group, lumbosacral region was examined.
      RESULTS: A total 33 bone metastases have been diagnosed out of 98 patients. The
      Sc result showed 26/33 metastatic cases, XR 19/33 and CT 22/33 cases. There were
      no false positive results for CT and XR. Results of CT have 11 and XR has 14
      false negatives out of 33 metastases. For XR the calculated sensitivity was 65.6,
      specificity was 100, diagnostic accuracy was 88.7, whereas for CT, sensitivity
      was 71.8, specificity was 100 and diagnostic accuracy was 90.8. When CT and XR
      were compared to detect bone metastases, results were not statistically
      significant (p>0.05). CONCLUSION: Our results suggest that 5mm slice CT is not
      superior than XR to detect metastatic bone lesions. Larger series comparing
      different slice thickness of CT are needed to clarify the issue.

PMID- 16951768
TI  - Does thymidine phosphorylase correlate with angiogenesis in intraductal carcinoma
      of the breast?
AB  - OBJECTIVE: To determine the association between thymidine phosphorylase (TP) and
      angiogenesis, and other conventional prognostic markers. We also evaluated
      interobserver and intraobserver reliability for TP expression in ductal
      carcinoma, to achieve a more consistent results. METHODS: Our study included all
      cases diagnosed in Adnan Menderes University Medical Faculty Hospital, Aydin,
      Turkey as invasive ductal carcinoma or ductal carcinoma in situ (DCIS) with
      proven component of (>30%), between January 2003 and February 2005. The total
      number of the cases was 27 and their median age was 50 years. All sections were
      stained using monoclonal antibody-TP and examined at x40 magnification. Either
      nuclear or cytoplasmic staining was accepted as positive. The histoscore (H
      score) was calculated for each specimen. The tumor stromal vascularity was
      assessed by monoclonal anti-CD34; and areas of intense vascularization were
      determined. Conventional immunohistochemical markers such as c-erb B2, Ki-67,
      estrogen and progesterone receptors and p53 were also applied to all slides.
      Three pathologists blindly examined each slide under 10 high-power fields (10
      HPF) for 2 times in a 2 months period. RESULTS: There was no significant
      association between stromal vascularity and TP staining of cancer cells (p=0.1)
      and no correlation was determined between H-scores for TP staining in ductal
      carcinoma and DCIS components (p=0.5). CONCLUSION: There was no significant
      correlation noted between stromal and periductal vascularity with the anti-CD34
      antibody was used. No significant correlation was identified between the TP H
      score and stromal or periductal vascularity.

PMID- 16951769
TI  - Carrier screening and prenatal detection of chronic granulomatous disease in
      Iran.
AB  - OBJECTIVE: To develop an application that is simple and reliable using the
      nitroblue tetrazolium (NBT) method that clearly differentiates chronic
      granulomatous disease (CGD) patients with heterozygous carriers in groups
      suspected with CGD. METHODS: This study was carried out in Shiraz University of
      Medical Sciences from October 2002 and March 2004. The study included 260 samples
      consisting of 123 children (2-24 months) and 106 neonates (<2 months), either
      suspected with bacterial infection or are immunodeficient, and 31 cord blood
      samples. Fifty healthy adult individuals were also diagnosed as normal control.
      Neutrophil reduction of NBT can be stimulated in vitro by protein kinase agonists
      such as phorbol myristate acetate (PMA), resulting to superoxide anion release.
      RESULTS: The PMA is an exceptionally powerful stimulant and when we used it in
      conjunction with adherence of glass slides, it causes transformation of nearly
      100% of all normal neutrophils, and reduces NBT to formazan deposits. Of 260
      blood samples, 12 unrelated CGD patients and 16 carriers of X-linked or autosomal
      recessive CGD patients were diagnosed. The carriers had a range of 15-75%
      stimulated neutrophils. CONCLUSION: We have established a PMA-stimulated NBT test
      for the detection of CGD patients, which clearly differentiate the CGD patients
      from heterozygote carriers. The results in the cord fetal blood samples indicate
      that this test may be used for antenatal diagnosis of affected boys, carrier
      females and autosomal recessive variants of CGD. The technique is simple, fast,
      inexpensive, and requires only a few microliters of blood.

PMID- 16951770
TI  - Metabolic hormones profile in 2 weeks old healthy infants of diabetic mothers.
AB  - OBJECTIVE: To determine the concentration of plasma leptin and other metabolic
      hormones in offspring of diabetic and none diabetic mothers after 2 weeks of age.
      The relationship between leptin and metabolic hormones was also investigated.
      METHODS: Included in the study were 79 newborns from the Neonatal Unit at King
      Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia from January 2004
      January 2005. The newborns were categorized into 3 main groups: the control
      group, consisting of 32 infants of non-diabetic mothers; the gestational diabetes
      mothers (GDM) group, consisting of 26 infants; and the frank diabetic mothers
      (FDM), consisting of 21 infants. Infants of diabetic mothers were further
      subdivided into those of dietary (d) or insulin (i) dependent mothers. Plasma
      leptin, insulin, cortisol and free thyroxin levels were measured by enzyme link
      immunosorbent assay. RESULTS: No significant difference in plasma leptin was
      observed between the studied groups. The GDM-d and FDM-d showed lower glucose
      versus controls (p<0.001 and p<0.05). There was significant correlation between
      leptin and glucose in the GDM group (r=0.18, p< 0.05) and with insulin in GDM-d
      on diet control (r=0.37, p< 0.01). CONCLUSION: After 2 weeks of life, no
      difference in plasma leptin between infants of diabetic and non-diabetic mothers
      was observed, which may be important for the stimulation of feeding behavior and
      acquisition of energy homeostasis. Significant association between plasma leptin
      and insulin in offspring of GDM supports the hypothesis that functional
      adipoinsular axis might exist in term newborns.

PMID- 16951771
TI  - Comparison of the automated Cobas Amplicor Mycobacterium tuberculosis assay with
      the conventional methods for direct detection of Mycobacterium tuberculosis
      complex in respiratory and extrapulmonary specimens.
AB  - OBJECTIVE: To evaluate the recently available Cobas Amplicor polymerase chain
      reaction (PCR) system for the detection of Mycobacterium tuberculosis complex
      (MTBC) in well-characterized clinical specimens and to compare the results with
      clinical classification, conventional culture and staining techniques. METHODS:
      Three hundred and forty-four clinical specimens consecutively received for
      culture of acid-fast bacilli by the laboratory of Zayed Military Hospital, Abu
      Dhabi, United Arab Emirates, from 2004 to 2005, were used in this study. Acid
      fast bacilli and culture for tuberculosis were compared with Cobas Amplicor PCR.
      RESULTS: The final diagnostic evaluation of the Cobas Amplicor MTB showed the
      followings: sensitivity 73.3%, specificity 99.4%, positive predictive value
      84.6%, negative predictive value 98.8% and with accuracy of 98.2% for the Cobas
      Amplicor MTB assay. CONCLUSION: The automated Cobas Amplicor MTB assay is
      suitable for routine use in clinical laboratories.

PMID- 16951772
TI  - Narcolepsy in Saudi Arabia. Demographic and clinical perspective of an under
      recognized disorder.
AB  - OBJECTIVE: To assess the clinical and polysomnographic features of narcolepsy in
      Saudis. METHODS: All patients diagnosed to have narcolepsy in the Sleep Disorders
      Center at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia
      between March 1998 and December 2005 based on the International Classifications
      of Sleep Disorders Diagnostic and Coding Manual criteria were included. A data
      entry form collecting the demographic, clinical features, medications, referring
      specialty, prior diagnoses and daytime sleepiness was used. All patients
      underwent polysomnography followed by multiple sleep latency. RESULTS: Forty
      seven patients with a mean age of 28.9 +/- 1.9 years were included. The mean age
      at onset of symptoms was 20.5 +/- 1.4 years. The interval between symptoms onset
      and diagnosis was 8.4 +/- 1.2 years. While 22 (46.8%) of the patients were
      referred to the sleep disorders clinic by different specialties, 25 (53.2%)
      patients sought an appointment in the sleep disorders clinic directly. Only 3
      patients were referred with the correct diagnosis. Nocturnal sleep quality was
      worse in narcoleptics with cataplexy compared to those without cataplexy.
      CONCLUSION: Saudi patients with narcolepsy have the same clinical presentation as
      reported in the Western literature. Narcoleptics with cataplexy had disturbed
      quality compared to narcoleptics without cataplexy. A long time was reported
      between symptoms onset and diagnosis, which may reflect the under-recognition of
      the problem among physicians.

PMID- 16951773
TI  - Cardiovascular disease risk factors in patients with confirmed cardiovascular
      disease.
AB  - OBJECTIVE: To assess the magnitude of the problem of cardiovascular risk factors
      in hospitalized patients, and to establish cardiovascular disease (CVD) risk
      factor profiles. METHODS: The study included 476 confirmed CVD patients selected
      by a multi stage stratified cluster random sampling technique in Tabriz Heart
      Center (Shaheed Madani Hospital), Tabriz, Iran from February 2004 to May 2005.
      After obtaining demographic information and performing physical examination,
      biochemical parameters were measured. Data was analyzed using the Statistical
      Package for Social Science version 10.05, where p value of <0.05 was considered
      significant. RESULTS: Obesity was the most common abnormality (93.5%) followed by
      diabetes mellitus (58.4%), low high-density lipoprotein cholesterol (HDL-c)
      (45.4%), low physical activity (41.6%), high total cholesterol (40.1%), high
      triglyceride (37.2%), high low-density lipoprotein cholesterol (30.7%), diastolic
      hypertension (28.4%), high systolic blood pressure (24.8%) and smoking (20%). Of
      the total number of patients, 93% had one risk factors for CVD, 43% had 2, 16%
      had 3, and 5% had 4 risk factors. The prevalence of lipid disorders in females
      was more than males except for low HDL-c (p<0.05). Between lipid profiles, only
      TG showed a correlation between age (p<0.05). It was noticed that obesity
      accompanied by lipid profile abnormalities as low serum levels of HDL-c and high
      level of TG, TC, and LDL-c were more seen in obese patients (p<0.05). CONCLUSION:
      This study revealed a high prevalence of risk factors in CVD patients; thus,
      urgent lifestyle modification is recommended.

PMID- 16951774
TI  - Spectrum of clinical disease in a series of hospitalized HIV-infected patients
      from southeast of Iran.
AB  - OBJECTIVE: To determine the pattern of opportunistic infections (OIs) and non
      infectious opportunistic diseases in hospitalized HIV-infected patients in
      Zahedan, southeast of Iran. METHODS: We retrospectively reviewed the records of
      52 HIV-infected patients (47 male, 5 female; age range, 21-54 years) who were
      admitted to Boo-Ali Hospital, Zahedan, Iran for evaluation and management of an
      HIV-related disorders from April 2000 to December 2005. RESULTS: Tuberculosis
      (TB) was the most common opportunistic infections (53.8%) followed by hepatitis C
      (11.5%), typhoid (9.6%), amebiasis (9.6%), candidal esophagitis (5.7%), acute
      bacterial pneumonia (3.8%), and cerebral toxoplasmosis (1.9 %). Most of the cases
      of TB were pulmonary (36.5%). Apart from other well-recognized OIs, 2 cases of
      HIV-associated lymphoma were encountered. Only 12 patients (23.07%) received
      antiretroviral therapy. Five patients (9.6%) died during hospital stay due to
      tuberculosis (4 cases) and typhoid (1 case). CONCLUSION: The findings show that
      opportunistic infections are common in HIV-infected patients in Zahedan,
      southeast of Iran. Tuberculosis remains the most common OIs and is the most
      common cause of death in these patients.

PMID- 16951775
TI  - Carriage of Staphylococcus aureus among Hajj pilgrims.
AB  - OBJECTIVE: To evaluate the prevalence of methicillin resistant Staphylococcus
      aureus (MRSA) carriage among a cohort of pilgrims during 2004 Hajj season.
      METHODS: Pilgrims attending the 2004 Hajj season were recruited and screened for
      carriage of MRSA. Standard microbiological techniques were used to screen for the
      presence of MRSA. RESULTS: Out of 411 individuals screened, 85 (20.6%) were
      positive for Staphylococcus aureus (S. aureus) of which only 6 (1.46 %) were
      MRSA. Four individuals (4.6%) had the S. aureus organism in both nasal and
      axillary swabs, while 7 individuals (8%) had the organism in their axillae only.
      The other 74 individuals (87.1%) had the organism in their nares only. The 6 MRSA
      isolates were positive for the mecA gene by polymerase chain reaction method.
      None of the pilgrims examined had any risk factors for community-acquired
      methicillin resistant S. aureus (CAMRSA). Overall, the prevalence of MRSA in the
      population of pilgrims examined was found to be low (1.46%) in comparison with
      most community based studies. CONCLUSION: A low rate of MRSA carriage was noticed
      among the screened cohort. Physicians treating patients suspected of S. aureus
      infection during the Hajj pilgrimage should bear in mind the possibility of
      community acquired - MRSA and should obtain appropriate samples for bacterial
      cultures and susceptibility testing so that antimicrobial agents could be
      introduced when necessary at a later stage.

PMID- 16951776
TI  - Pattern of medical diseases and determinants of prognosis of hospitalization
      during 2005 Muslim pilgrimage Hajj in a tertiary care hospital. A prospective
      cohort study.
AB  - OBJECTIVE: To document the pattern of medical diseases necessitating admission in
      a tertiary care hospital during Muslim pilgrimage (Hajj). To assess the risk
      factors associated with mortality during hospitalization. METHODS: The study was
      conducted at Al Noor Specialist Hospital, a 550-bed tertiary care teaching
      hospital, in Makkah, KSA. The participants included all Hajj patients admitted in
      the Department of Medicine in a 5-week period (January 3 to February 6, 2005)
      during the 2005 (1425 AH) Hajj. Information about demographics; past medical
      history; pre-Hajj functional status; presence of language barrier and translator
      availability; diagnosis for admission and complications during hospitalization
      including mortality was obtained prospectively using a standardized form.
      RESULTS: Six hundred and eighty-nine patients, belonging to 49 countries, with
      mean age of 62 years and male:female ratio of 1.8:1 were admitted. Two hundred
      twenty (31.9%) had diabetes mellitus, 256 (37.2%) had hypertension, 219 (31.8%)
      had cardiac disease, and 103 (14.9%) patients had chronic lung disease. Of the
      449 (65.2%) patients assessed, 284 (63.2%) patients had language barrier, and
      translator was not available for 152 (53.5%) of them. Pre-Hajj functional status
      assessment of 240 patients showed that 20 (8.3%) required assistance in
      performing activities of daily living (ADL), and 40 (16.7%) could not walk for
      half kilometer without difficulty. Common causes of morbidity were: 235 (34.1%)
      cardiovascular, 137 (19.9%) infectious and 85 (12.3%) neurological diseases. One
      hundered and fourteen (16.5%) patients died, with the common causes being
      pneumonia (28 patients), acute coronary syndrome (21), and stroke (20). The risk
      factors associated with higher mortality were older age (65 +/- 1 versus 61 +/-
      0.6 years, p=0.008), prior history of chronic lung disease (crude odds ratio,
      1.81, p=0.034), dependence in any ADLs (4.90, p=0.025), inability to ambulate for
      half kilometer without difficulty (4.17, p=0.017) and non-availability of
      translator for patients with language barrier (5.51, p<0.0001). CONCLUSION: Most
      patients were elderly with high prevalence of chronic medical disorders. Non
      infectious diseases accounted for most morbidity and mortality. Pre-Hajj
      functional assessment should be carried out to identify patients at high risk of
      mortality. Provision of translator services for patients with language barrier is
      essential to improve future outcomes.

PMID- 16951777
TI  - The prevalence and the age at the onset of menopause in Turkish women in rural
      area.
AB  - OBJECTIVE: To find out the prevalence of natural menopause among Turkish women
      according to age and certain demographic variables in a specific rural area.
      METHODS: This cross sectional study was carried out in Silivri district of
      Istanbul, Turkey between January and May 2000. Included in the study were 845
      women between the ages of 30-60 years, not undergoing any hormonal replacement,
      living in the villages of Silivri district, Istanbul, Turkey. The participants
      were asked for their ages, level of education, number of pregnancies, age at
      menarche, presence of menstruation, age at the onset of menopause, physical
      activity outside home and the use of oral contraceptives. Females declaring at
      least one year of amenorrhea were accepted as being in menopause. RESULTS: The
      median age for menopause was 47 years. Of the total 845 participants, 326 women
      were found to be in natural menopause. The prevalence of menopause was estimated
      as 8.6% for females younger than 40 years, 31.8% for females between the ages 40
      45 years and 80.9% among females older than 45 years. Any of the variables
      questioned in our study have an effect on premature onset of menopause, but we
      found that never been pregnant (p=0.037, odd ratio (OR)=2.221, 95% confidence
      interval (CI)=1.048, 4.707) reduces the reproductive period, and the age at
      menarche younger than 13 prevents early menopause (p=0.000, OR=0.336, 95%
      CI=0.195, 0.579). Furthermore, both lead to early onset of menopause. Hazard
      ratios of the variables that have an effect on the onset of early menopause are
      calculated as 2:10 (95% CI=1.01, 4.39) for those who were never been pregnant and
      1:10 for those with the menarche ages over 13 years (95% CI=0.68, 1.78).
      CONCLUSION: There was a noticeably high percentage of females (8.6%) younger than
      40 years who were entering menopause. On the other hand, an early onset of
      natural menopause among Turkish women living in this rural area was found to be
      associated with never been pregnant and their age of menarche.

PMID- 16951778
TI  - Anticardiolipin antibody in women with recurrent spontaneous miscarriage.
AB  - OBJECTIVE: To determine the association between the presence of anticardiolipin
      antibody (ACA) and history of recurrent spontaneous miscarriage. Also, to
      evaluate the association between raised ACA and activated partial thromboplastin
      time (APTT). METHODS: This is a case-control study which was carried out in
      Basrah Hospital for Maternity and Children, Basrah, Iraq during January to
      September 2004 on 91 women with recurrent spontaneous miscarriage, matched with
      109 women with no history of pregnancy wastage. Sera were collected from these
      200 women and analyzed for ACA by enzyme linked immunosorbent assay (ELISA).
      RESULTS: In women with pregnancies that ended with a loss, 17.6% were positive of
      ACA, compared with none among the control group. Women with 4 or more
      miscarriages had almost higher percentages of ACA (26.3% and 22.2%) than women
      with only 3 miscarriages (13%) but with no statistical significance. Prolonged
      APTT was detected among 18.8% of patients having positive ACA while only 1.6% of
      patients who were negative for this antibody. CONCLUSION: A significant
      association was observed between recurrent spontaneous miscarriage and the
      presence of ACA. Also, there was a significant relationship between positive ACA
      and prolonged APTT.

PMID- 16951779
TI  - Higher prevalence in young population and rightward shift of colorectal
      carcinoma.
AB  - OBJECTIVE: To report the pattern, subsite distribution and histological features
      of colorectal cancer in a University Hospital in Riyadh. METHODS: The study was
      carried out in King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia,
      where the medical records of patients diagnosed to have colorectal carcinoma were
      retrieved spanning a 5-year period from 1999 through 2004. The demographic data,
      primary location and extent of the lesion, and various pathologic characteristics
      were analyzed. RESULTS: Fifty-seven patients with colorectal carcinoma were
      included; 45 men and 12 women, age range 21-76 years (mean 44 years). Thirty-six
      (63%) subjects were found to be younger than 40 years, whereas 33 (57.8%) cases
      had right sided and 24 (42.2%) left sided colon cancers. Eighteen (31.5%)
      patients presented with early (I, II) and 39 (68.5%) with late (III, IV) stage.
      Dukes B and C were reported in 53 (92.9%) patients and out of those, 30 cases
      presented with right sided colonic carcinoma. CONCLUSION: There is a profound
      rightward shift of colorectal carcinoma compounded with a rising incidence of
      advanced lesions in younger age group.

PMID- 16951780
TI  - A study of knowledge and attitudes towards the use of evidence-based medicine
      among primary health care physicians in Bahrain.
AB  - OBJECTIVE: A study of perceptions and attitudes towards the use of evidence-based
      medicine (EBM) among family physicians in Bahrain. METHODS: A systematically
      developed, anonymous, self administered 13 item questionnaire was mailed to 124
      Bahraini family physicians in the Ministry of Health, Bahrain between January and
      April 2004. The response rate was 65%. Data were analyzed using the Statistical
      Package for Social Sciences (Windows version 11.00). RESULTS: The respondents
      (n=81) were mainly female (65.4%) with a mean age of 40 (SD 7.7) years, with 12.7
      (SD 8.3) years since graduation. Forty-two percent had attended EBM workshops and
      61% claimed to use EBM in their practice. Those who had attended a workshop were
      more likely to assert that they were practicing EBM (82% versus 47%; p=0.001).
      Less than 10% selected patient s choice as a component of EBM. The 81.5% of
      respondents agreed their patients were willing to participate in decision making
      but 50% felt that only 10-25% of their patients were capable. No time (53.1%) and
      no ready access to resources (73.5%) were the most cited barriers, 32% of
      respondents agreed that EBM is not applicable to their culture. CONCLUSION: Most
      family physicians in Bahrain claimed to use EBM in their practice, particularly
      if they had attended an EBM workshop. However, most of them did not consider
      patients values as a component of EBM. A substantial minority considered that EBM
      is inapplicable to their culture.

PMID- 16951781
TI  - The use of a molecular technique for the detection of porcine ingredients in the
      Malaysian food market.
AB  - OBJECTIVE: To develop a molecular technique that is fast and reliable in
      detecting porcine contamination or ingredients in foods. METHODS: The method
      applied involved DNA amplification using polymerase chain reaction (PCR)
      technology. Thus, the sequence of a certain gene found uniquely in pork was
      identified and its sequence was used to design specific primers for the PCR. The
      extraction of DNA was optimized in respect to PCR and detection limits were
      established. The optimized method was then used to identify pork in food products
      obtained from various local hypermarkets. The latest results were confirmed in
      triplicates on the 20th April 2006 at the Molecular Biology Laboratory,
      International Islamic University, Malaysia. RESULTS: The method was shown to be
      robust and reliable. Out of 30 food samples not expected to contain pork
      material, 3 samples were shown to be contaminated with pork material; 2
      chocolates and one chicken nugget. CONCLUSION: We observed that 2 food products
      that were labeled as halal showed positive for porcine ingredients, while another
      that did not have any halal logo but originated from outside Malaysia and
      exported to many Middle Eastern nations also showed positive.

PMID- 16951782
TI  - Arterial homograft and medical therapy in pseudoaneurysm of infrarenal aorta
      concomitant with recurrent right ventricular thrombus in Behcet's disease.
AB  - Pseudoaneurysm of the infrarenal aorta due to Behcet s disease is very rare. We
      report a case of pseudoaneurysm associated with Behcet s disease in a 17-year-old
      boy with a recurrent right ventricular thrombus successfully treated with
      revascularization using arterial homograft patch. Echocardiography examination
      revealed a right ventricular mass, thought to be a thrombus in an unusual
      location. Postoperatively, the findings of the pathologic examination confirmed
      the mass as a thrombus. When the patient was subsequently re-admitted to the
      emergency unit with complaints of severe abdominal pain, fever, fatigue, sinus
      tachycardia, and a pulsating and tender abdominal mass, a right ventricular
      thrombus and a large pseudoaneurysm of the abdominal aorta were found on
      echocardiography and angiography. The patient underwent resection of the aortic
      aneurysm and aortoplasty, using arterial homograft patch, and received
      immunosuppressive and anticoagulation therapy. The thrombus of the right
      ventricle disappeared 4 months later. This case indicates that a right
      ventricular thrombosis in Behcet s disease may be managed by medical therapy.

PMID- 16951783
TI  - Satellite implantation of the skin with malignant melanoma.
AB  - We report a 68-year-old female patient referred to the Surgical Department of
      Erbil Teaching Hospital university hospital, Erbil, Iraq with the diagnosis of
      malignant melanoma of the right upper thigh of one-year duration. Six months
      after primary lesion, she developed a satellite skin nodule of malignant melanoma
      over the unhealthy skin of the anterior abdominal wall in direct contact with the
      primary lesion. She also had a pendulous abdominal wall. This kind of spread of
      melanoma is unusual, and of non-classical route. We also discussed herein,
      similar cases admitted to our hospital.

PMID- 16951784
TI  - Isolated brain stem tuberculoma presenting with one and a half syndrome.
AB  - In this report, we describe a patient with left conjugate gaze palsy and
      internuclear ophthalmoplegia on the opposite gaze one-and-a-half-syndrome [11/2
      syndrome]. Magnetic resonance imaging of the brain showed nodular enhancing brain
      stem lesions. After excluding other potential diseases, tuberculoma was thought
      to be the underlying etiology. Recovery was achieved 8 weeks after initiation of
      anti-tuberculous anti-TB therapy. The isolated nature of the tuberculoma and the
      association with this rare syndrome is highlighted.

PMID- 16951785
TI  - Ovarian mucinous cystadenocarcinoma of low malignant potential associated with a
      mature cystic teratoma.
AB  - The development of mucinous cystadenocarcinoma of low malignant potential in a
      mature cystic teratoma is rare. We report a 36-year-old single female presented
      with abdominal distension and was found to have a huge pelvic/abdominal mass.
      Ultrasound revealed a huge cystic ovarian mass with no ascites. Laparotomy and
      left oophorectomy was performed to the mass. Histology revealed mucinous
      cystadenocarcinoma of low malignant potential in a mature cystic teratoma.

PMID- 16951786
TI  - Crossing renal vessel causing ureteropelvic junction obstruction.
AB  - Ureteropelvic junction UPJ obstruction is caused by the presence of an
      aperistaltic dysplastic segment at the UPJ. Besides this intrinsic etiology,
      extrinsic factors, mainly crossing vessels, maybe the causative factor. The
      controversy regarding the functional significance of vessels crossing at the UPJ
      is not a new one, though this debate has been resurrected in recent years because
      of improved detection due to the advent of advanced imaging techniques such as
      multidetector row computed tomography MDCT and fast magnetic resonance imaging.
      We present a similar case where MDCT proved the crossing renal vessel to be the
      cause for UPJ obstruction.

PMID- 16951787
TI  - Factor V Leiden mutation and deep venous thrombosis in a patient with
      hypereosinophilic syndrome.
AB  - Idiopathic hypereosinophilic syndrome is a rare condition characterized by
      extremely high peripheral blood eosinophil counts. Patients with idiopathic
      hypereosinophilic syndrome are at increased risk for thrombosis. The coexistence
      of idiopathic hypereosinophilic syndrome with other thrombotic disease is rare.
      We present an additional case of idiopathic hypereosinophilic syndrome and factor
      V Leiden mutation, which lead to deep vein thrombosis.

PMID- 16951788
TI  - Pityriasis rubra pilaris in association with hepatitis A.

PMID- 16951789
TI  - Successful initial treatment with caspofungin alone for hepatosplenic candidiasis
      in a patient with acute myeloblastic leukemia.

PMID- 16951790
TI  - Intestinal obstruction. A rare delayed presentation of traumatic diaphragmatic
      hernia.

PMID- 16951791
TI  - Patients adherence to treatment and knowledge about chronic obstructive pulmonary
      disease.

PMID- 16951792
TI  - Follow-up of hepatitis C virus infected patients.

PMID- 16951793
TI  - Diagnostic role of pediatric flexible bronchoscopy in Down's syndrome associated
      with congenital heart disease.

PMID- 16951794
TI  - Effects of statins on bone mineral density.

PMID- 16951795
TI  - Obstructed labor. A real problem in Yemeni s rural areas.

PMID- 16951796
TI  - Symptomatology of menopause among middle-aged women in 3 impoverished Lebanese
      communities.

PMID- 16951797
TI  - Is the risk of multiple cesarean sections similar to that of a single or 2
      previous cesarean sections in the Middle East?

PMID- 16951798
TI  - Evaluation of the dead space to tidal volume ratio as a predictor of extubation
      failure.
AB  - OBJECTIVE: The objective of this study was to evaluate the ratio of dead space to
      tidal volume (VD/VT) as a predictor of extubation failure of children from
      mechanical ventilation. METHODS: From September 2001 to January 2003 we studied a
      cohort consisting of all children (1 day-15 years) submitted to mechanical
      ventilation at a pediatric intensive care unit who were extubated and for whom
      pre-extubation ventilometry data were available, including the VD/VT ratio.
      Extubation success was defined as no need for any type of ventilatory support,
      invasive or otherwise, within 48 hours. Patients who tolerated extubation, with
      or without noninvasive support, were defined as success-R and compared with those
      who were reintubated. Statistic analysis was based on a VD/VT cutoff point of
      0.65. RESULTS: During the study period 250 children received mechanical
      ventilation at the pediatric intensive care unit. Eighty-six of these children
      comprised the study sample. Twenty-one children (24.4%) met the criteria for
      extubation failure, with 11 (12.8%) of these requiring non-invasive support and
      10 (11.6%) reintubation. Their mean age was 16.8 (+/-30.1) months (median = 5.5
      months). The mean VD/VT ratio for all cases was 0.62 (+/-0.18). Mean VD/VT ratios
      for patients with successful and failed extubations were 0.62 (+/-0.17) and 0.65
      (+/-0.21) (p = 0.472), respectively. Logistic regression failed to reveal any
      statistically significant correlation between VD/VT ratio and success or failure
      of extubation (p = 0.8458), even for patients who were reintubated (p = 0.5576).
      CONCLUSIONS: In a pediatric population receiving mechanical ventilation due to a
      variety of etiologies, the VD/VT ratio was unable to predict the populations at
      risk of extubation failure or of reintubation.

PMID- 16951799
TI  - Prevalence of symptoms of asthma, rhinitis, and atopic eczema among Brazilian
      children and adolescents identified by the International Study of Asthma and
      Allergies in Childhood (ISAAC) - Phase 3.
AB  - OBJECTIVES: To determine the prevalence of symptoms of asthma, rhinitis, and
      atopic eczema among schoolchildren aged 6 to 7 years and adolescents aged 13 to
      14 years in 20 Brazilian cities by using the standardized ISAAC written
      questionnaire, and to assess the association of this prevalence with latitude,
      altitude and average annual temperature of collaborating centers. METHODS:
      Schoolchildren and adolescents from five Brazilian regions participated in the
      study, totaling 23,422 ISAAC questionnaires answered by schoolchildren's parents
      and 58,144 questionnaires answered by adolescents. The values for latitude,
      altitude and average annual temperature were obtained from the Brazilian
      Institute of Geography and Statistics. RESULTS: The mean prevalence rates among
      schoolchildren and adolescents were respectively 24.3 and 19.0% for active
      asthma; 12.6 and 14.6% for rhinoconjunctivitis; and 8.2 and 5.0% for atopic
      eczema. A significant negative association was observed between latitude and
      physician-diagnosed asthma among schoolchildren, severe asthma, physician
      diagnosed asthma, eczema and atopic eczema among adolescents. No association with
      altitude was found. CONCLUSIONS: The prevalence of asthma, rhinitis and atopic
      eczema in Brazil varies considerably. Higher prevalence rates, especially of
      asthma and eczema, were found at centers located closer to the equator.

PMID- 16951800
TI  - Etiology of exanthema in children in a dengue endemic area.
AB  - OBJECTIVE: To study the etiology of exanthema cases, with or without fever, in
      children seen in the emergency room of a hospital located in a region where
      dengue is endemic. METHODS: Enrollment took place between 21/09/2001 and
      20/09/2002 and included 95.9% (71/74) of children presenting with exanthema at
      the emergency room of the Hospital Universitario de Campo Grande, MS (4.1%
      refusals). After the children had had their details taken and entered on the
      study protocol, they were subjected to physical examination followed by
      collection of blood samples for blood testing with platelet counts and serology
      (IgM and IgG); initially for dengue, rubella and toxoplasmosis and then, in
      negative cases, serology was also run for parvovirus, herpes virus type 6 and
      measles. RESULTS: Laboratory diagnoses were confirmed by means of IgM antibody
      assay in 88.7% of the cases investigated: dengue (77.5%), herpes virus type 6
      (8.4%), parvovirus (2.8%) and in eight patients diagnosis was inconclusive
      (11.3%). On this occasion no positive serology (IgM) was observed for measles,
      rubella or toxoplasmosis. The most common clinical manifestations among the
      dengue patients were: fever, itching, prostration, myalgia and positive
      tourniquet test results. In 58.4% (32/55) of those cases diagnosed with dengue,
      the tourniquet test was positive, which was a statistically significant
      difference when compared with the remainder of the sample. CONCLUSIONS: When
      children present with exanthema, it is possible that dengue is the primary
      causative disease, depending on the epidemiology of the location. Constant
      control of epidemiological and serological surveillance of exanthematous diseases
      is necessary.

PMID- 16951801
TI  - Development of a questionnaire for the assessment of sexual abuse in children and
      estimation of its discriminant validity: a case-control study.
AB  - OBJECTIVES: To develop an instrument to determine the probability of child sexual
      abuse and to estimate the questionnaire's discriminant validity. METHODS: Case
      control study of 201 children seen at pediatric clinics and referral centers for
      the victims of sexual violence, between March and November 2004. Cases comprised
      children who had either been reported or suspected of being sexually abused and
      controls comprised children with no such suspicion. We applied a questionnaire to
      a parent or guardian of each child that consisted of 18 items, each with five
      Likert scale responses, dealing with the behavior and physical and emotional
      symptoms exhibited by the children. We excluded nine children for lack of
      sphincter control. One question was discarded since very few people replied to
      it. We evaluated the discriminant validity and internal consistency of the items,
      calculating correlation coefficients (Pearson, Spearman and Goodman-Kruskal),
      Cronbach's alpha coefficient and area under the ROC curve. We calculated
      likelihood ratios and positive predictive values for the five items on the
      questionnaire that performed best. RESULTS: The questionnaire comprises the five
      items that best discriminate sexually abused children from non-abused children in
      two contexts. The score resulting from the sum of responses weighted at 0 to 4
      points (overall amplitude of 0 to 20) indicates the post-test probability of
      sexual abuse by means of the application of Bayes theorem (likelihood ratios).
      CONCLUSIONS: The instrument is easy to apply and helps in the identification of
      sexual abuse victims. A cutoff point was defined to indicate the probability of
      sexual abuse, which can be very useful to guide management of children.

PMID- 16951802
TI  - Chagas disease in Mexico: an analysis of geographical distribution during the
      past 76 years--a review.
AB  - Literature from 1928 through 2004 was compiled from different document sources
      published in Mexico or elsewhere. From these 907 publications, we found 19
      different topics of Chagas disease study in Mexico. The publications were
      arranged by decade and also by state. This information was used to construct maps
      describing the distribution of Chagas disease according to different criteria:
      the disease, vectors, reservoirs, and strains. One of the major problems
      confronting study of this zoonotic disease is the great biodiversity of the
      vector species; there are 30 different species, with at least 10 playing a major
      role in human infection. The high variability of climates and biogeographic
      regions further complicate study and understanding of the dynamics of this
      disease in each region of the country. We used a desktop Genetic Algorithm for
      Rule-Set Prediction procedure to provide ecological models of organism niches,
      offering improved flexibility for choosing predictive environmental and
      ecological data. This approach may help to identify regions at risk of disease,
      plan vector-control programs, and explore parasitic reservoir association. With
      this collected information, we have constructed a data base: CHAGMEX, available
      online in html format.

PMID- 16951803
TI  - Field trials of low dose Bayluscide on snail hosts of schistosome and selected
      non-target organisms in sahelian Cameroon.
AB  - More than 85% of all cases of schistosomiasis in Cameroon occur in the northern
      sahelian half of the country representing 20% of the population. Several workers
      have advocated the integrated approach to schistosomiasis control, including
      snail control, but the death and decay of aquatic organisms, and fish kill that
      often follows Bayluscide application at the dose of 1 g/m3 decrease its
      acceptability. The present study was designed to assess the effect of lower
      Bayluscide doses on snail host and non-target fish, frog, the tadpole kill.
      Bayluscide was applied to study ponds at concentrations of 0, 0.25, 0.5, and 1
      g/m3 (ppm). Pre and post application assessment of snails hosts of schistosomes,
      fish, frog, and tadpole kill were carried out. All 0.25, 0.5, and 1 g/m3
      Bayluscide concentrations reduced snail population significantly. Bayluscide
      concentration of 0.50 g/m3 applied in two rounds of 0.25 g/m3 resulted in high
      snail mortality and low lethality to fish, frogs, and tadpoles. Further studies
      are needed to assess the cost-effectiveness of Bayluscide in the control of
      schistosomiasis following the simplified approach.

PMID- 16951804
TI  - Levels of complement C3 and C4 components in Amerindians living in an area with
      high prevalence of tuberculosis.
AB  - The levels of complement C3 and C4 components were determined in non-indigenous
      (creoles) and indigenous (Warao) populations, the latter with an extremely high
      tuberculosis (TB) rate. Serum samples from 209 adults were studied and classified
      in 4 groups taking into account tuberculin skin tests (TST): (1) the group of
      Warao patients (58 positive for the TST, WP TST+ and 9 negative for the TST, WP
      TST-), (2) the group of creole patients (34 positive for the TST, CP TST+ and 9
      negative for the TST, CP TST-), (3) the group of healthy Warao controls (38
      positive and 14 negative for TST, WC TST+ and WC TST-, respectively), (4) the
      creole controls (26 positive and 21 negative for the TST, CC TST+ and CC TST-,
      respectively). With respect to the results concerning the measurement of both
      complement C3 and C4 components with the exception of the WC TST and the CC
      groups, the WP TST+ and WP TST- as well as WC TST+ groups showed a significant
      frequency of individuals with decreased levels of complement C3 component (20.6,
      33.3, and 26.3%, respectively) and also C4 component (12.0, 11.1, and 13.3%,
      respectively) in comparison to both creole patients (CP TST+, 8.82% and CP TST-,
      0% and CP TST+, 5.88% and CP TST-, 0%) for C3 and C4, respectively. The study of
      these parameters carried out in 15 Warao subjects with active infection, before
      and after anti-TB chemotherapy,statisticallyconfirmedthat the effective
      chemotherapy did not restore normal levels of the complement C3 and C4 components
      among Warao patients. Aditional tests for hepatitis B or hepatitis C infection,
      and the profile of the hepatic proteins were not associated to the deficiency in
      production of the complement components. In conclusion, the results show that
      within the Warao population, a high percentage of subjects exhibit decreased
      levels of both complement C3 and C4 components independent of latent or active
      infection and the status of TST.

PMID- 16951805
TI  - Schistosoma mansoni major egg antigen Smp40: molecular modeling and potential
      immunoreactivity for anti-pathology vaccine development.
AB  - The pathogenesis of Schistosoma mansoni infection is largely determined by host T
      cell mediated immune responses such as the granulomatous response to tissue
      deposited eggs and subsequent fibrosis. The major egg antigens have a valuable
      role in desensitizing the CD4+ Th cells that mediate granuloma formation, which
      may prevent or ameliorate clinical signs of schistosomiasis.S. mansoni major egg
      antigen Smp40 was expressed and completely purified. It was found that the
      expressed Smp40 reacts specifically with anti-Smp40 monoclonal antibody in
      Western blotting. Three-dimensional structure was elucidated based on the
      similarity of Smp40 with the small heat shock protein coded in the protein
      database as 1SHS as a template in the molecular modeling. It was figured out that
      the C-terminal of the Smp40 protein (residues 130 onward) contains two alpha
      crystallin domains. The fold consists of eight beta strands sandwiched in two
      sheets forming Greek key. The purified Smp40 was used for in vitro stimulation of
      peripheral blood mononuclear cells from patients infected with S. mansoni using
      phytohemagglutinin mitogen as a positive control. The obtained results showed
      that there is no statistical difference in interferon-g, interleukin (IL)-4 and
      IL-13 levels obtained with Smp40 stimulation compared with the control group (P >
      0.05 for each). On the other hand, there were significant differences after Smp40
      stimulation in IL-5 (P = 0.006) and IL-10 levels (P < 0.001) compared with the
      control group. Gaining the knowledge by reviewing the literature, it was found
      that the overall pattern of cytokine profile obtained with Smp40 stimulation is
      reported to be associated with reduced collagen deposition, decreased fibrosis,
      and granuloma formation inhibition. This may reflect its future prospect as a
      leading anti-pathology schistosomal vaccine candidate.

PMID- 16951806
TI  - Molecular characterization of Leptospira sp. strains isolated from human subjects
      in Sao Paulo, Brazil using a polymerase chain reaction-based assay: a public
      health tool.
AB  - A polymerase chain reaction (PCR)-based assay which amplifies repetitive DNA
      elements present within bacterial genomes was used to characterize and
      differentiate Leptospira sp. Thirty-five strains from a reference culture
      collection and 18 clinical isolates which had been previously analyzed by cross
      agglutinin absorption test (CAAT) were evaluated by this technique. PCR results
      from analysis of the reference culture collection showed no bands corresponding
      to serogroups Australis, Autumnalis, Bataviae, Celledoni, Cynopteri, Djasiman,
      Panama, Pomona, Pyrogenes, and Tarassovi. However, the PCR method was able to
      clearly discriminate the serogroups Andamana, Ballum, Canicola, Grippotyphosa,
      Hebdomadis, Icterohaemorrhagiae, Javanica, Sejroe, Semaranga, and Shermani.
      Clinical isolates previously characterized by CAAT as serovar Copenhageni,
      serovar Castellonis, and as serovar Canicola were in agreement with PCR results.
      The clinical isolate previously characterized as serovar Pomona was not
      differentiated by PCR. Forty additional clinical isolates from patients with
      leptospirosis obtained in Sao Paulo, Brazil were also evaluated by this PCR
      method. Thirty-nine of these were determined to belong to serogroup
      Icterohaemorrhagiae (97.5%) and one to serogroup Sejroe (2.5%). These results
      demonstrate that the PCR method described in this study has utility for rapid
      typing of Leptospira sp. at the serogroup level and can be used in
      epidemiological survey.

PMID- 16951807
TI  - Environmental management for the control of Triatoma dimidiata (Latreille, 1811),
      (Hemiptera: Reduviidae) in Costa Rica: a pilot project.
AB  - An ecological control method, using environmental management operations, based on
      biological and behavioral characteristics of Triatoma dimidiata (Latreille,
      1811), was implemented as a pilot project in an area of Costa Rica where the bug
      is prevalent. The sample was represented by 20 houses with peridomestic colonies
      (two also had indoor infestation), divided in two equivalent groups of 10 each.
      In one group we intervened the houses, i.e. all objects or materials that were
      serving as artificial ecotopes for the bugs were removed, and the second group
      was used as control houses. After a year of periodic follow up, it became evident
      that in those houses with a modified environment the number of insects had
      decreased notoriously even after the first visits and this was more evident after
      a period of 12.5 to 13.5 months in which no insects were detected in eight of the
      houses. It also became clear that in this group of houses, recolonization by wild
      bugs from the surrounding areas, became more difficult, probably due to the
      absence of protection from bug predators. In the control houses, with the
      exception of three in which the inhabitants decided to intervene on their own,
      and another house with a peculiar situation, the insect populations remained the
      same or even showed a tendency to increase, as confirmed at the end of the
      experiment. We believe that the method is feasible, low costing and non
      contaminating. It could be used successfully in other places where T. dimidiata
      is common and also in countries where other species colonize peridomestic areas
      of homes. Environmental management of this kind should seek the participation of
      the members of the communities, in order to make it a more permanent control
      measure.

PMID- 16951808
TI  - Synergism between plant extract and antimicrobial drugs used on Staphylococcus
      aureus diseases.
AB  - Searches for substances with antimicrobial activity are frequent, and medicinal
      plants have been considered interesting by some researchers since they are
      frequently used in popular medicine as remedies for many infectious diseases. The
      aim of this study was to verify the synergism between 13 antimicrobial drugs and
      8 plant extracts--"guaco" (Mikania glomerata), guava (Psidium guajava), clove
      (Syzygium aromaticum), garlic (Allium sativum), lemongrass (Cymbopogon citratus),
      ginger (Zingiber officinale), "carqueja" (Baccharis trimera), and mint (Mentha
      piperita)--against Staphylococcus aureus strains, and for this purpose, the disk
      method was the antimicrobial susceptibility test performed. Petri dishes were
      prepared with or without dilution of plant extracts at sub-inhibitory
      concentrations in Mueller-Hinton Agar (MHA), and the inhibitory zones were
      recorded in millimeters. In vitro anti-Staphylococcus aureus activities of the
      extracts were confirmed, and synergism was verified for all the extracts; clove,
      guava, and lemongrass presented the highest synergism rate with antimicrobial
      drugs, while ginger and garlic showed limited synergistic capacity.

PMID- 16951809
TI  - Evaluation of adenosine deaminase seric activity in the diagnosis of bovine
      tuberculosis.
AB  - Determination of seric levels of adenosine deaminase (ADA), an enzyme produced by
      monocytes/macrophages and lymphocytes, has been used in the diagnosis of human
      tuberculosis (TB). In the present study, ADA seric activity was evaluated
      comparatively to the comparative tuberculin test in the diagnosis of bovine
      tuberculosis. Two hundred fifty-six cattle were classified by origin and by the
      comparative tuberculin test as TB-positive animals (n = 52, from herds where the
      Mycobacterium bovis had previously been isolated), and TB-negative animals (n =
      204, TB-free herds). The mean ADA seric value from the TB-positive group (4.45 +/
      2.33 U/L) was significantly lower (p = 0.008) than that observed in sera from
      the TB-negative group (6.12 +/- 4.47 U/L). When animals from a herd with clinical
      cases of enzootic bovine leukosis of TB-negative group were withdrawn from
      analysis, the mean ADA seric values of TB-negative group (5.12 +/- 3.75 U/L) was
      not significantly different anymore from that of the TB-positive group (p =
      0.28). There was no agreement in the diagnosis of bovine TB between comparative
      tuberculin test and determination of ADA seric values, using two different cutoff
      points, being 6.12 U/L and 15.0 U/L, (kappa = -0.086 and kappa = -0.082,
      respectively). In conclusion, the determination of ADA seric activity was not a
      good auxiliary test for bovine TB, because it was not able to distinguish between
      TB-positive and TB-negative animals.

PMID- 16951810
TI  - Related factors to human toxocariasis in a rural community of Argentina.
AB  - The objective of this study was to evaluate the relationship between toxocariasis
      frequency and demographic, environmental, sanitary variables, eosinophylia, and
      other intestinal parasites in a rural population of Argentina. Serological
      examination of 100 individuals was carried out by using ELISA technique for the
      detection of anti-toxocara antibodies. Eosinophiles in peripheral blood, presence
      of intestinal parasites, and demographic, environmental, and socio-cultural data
      were evaluated. Eighty-one feces samples of dogs belonging to the studied people
      were analyzed to detect eggs of Toxocara canis. Thirty of them were from 30 dogs
      and 51 were pools from dog feces. Samples of dirt from around the homes (n: 47)
      and from public park (n: 4) were taken. To determine the associations, the c(2)
      and Fisher tests were used. The seroprevalence was 23%. Eosinophilia in
      peripheral blood was detected in 86.95% seropositive individuals and in 37.66%
      seronegative individuals (p < 0.001, OR = 11.03). Of the 23 people with positive
      serology, 69.56% had at least one intestinal parasite. All individuals with
      positive serology had dogs in their homes. Among the dog owners there was a
      significant association between the presence of anti-toxocara antibodies and home
      flooding. Eggs of T. canis were detected in the feces of 5/81 dogs and three of
      these dogs belonged to individuals with positive serology. Eggs of Toxocara spp.
      were found in 41.17% of the dirt samples, eight of which came from the area
      surrounding the homes of individuals with positive serology (p = 0.032; OR =
      4.36). Taking into account all the variables influencing the frequency of
      toxocariasis in this population, the implementation of Public Health programs
      specifically focused on anti-parasitic treatment of dogs is recommended.

PMID- 16951811
TI  - Early infection and asymptomatic spread of hepatitis A virus in a public child
      care center in Rio de Janeiro, Brazil: should attending children under two years
      of age be vaccinated?
AB  - A cross-sectional study was conducted in order to identify hepatitis A virus
      (HAV) serological markers in 418 individuals (mean age, 16.4 years; range, 1
      month-80 years) at a public child care center in Rio de Janeiro, Brazil, as well
      as to analyze risk factors and determine circulating genotypes. Serum samples
      were tested using an enzyme immunoassay. Reverse transcription polymerase chain
      reaction (RT-PCR) was used to detect and characterize HAV RNA, and sequencing was
      performed. Anti-HAV antibodies and IgM anti-HAV antibodies were detected,
      respectively, in 89.5% (374/418) and 10.5% (44/418) of the individuals tested.
      Acute HAV infection in children was independently correlated with crawling (p <
      0.05). In 56.8% (25/44) of the IgM anti-HAV-positive individuals and in 33.3%
      (5/15) of the IgM anti-HAV-negative individuals presenting clinical symptoms, HAV
      RNA was detected. Phylogenetic analysis revealed co-circulation of subgenotypes
      IA and IB in 93.3% (28/30) of the amplified samples. In present study, we verify
      that 79% (30/38) of children IgM anti-HAV-positive were asymptomatic. In child
      care centers, this asymptomatic spread is a more serious problem, promoting the
      infection of young children, who rarely show signs of infection. Therefore,
      vaccinating children below the age of two might prevent the asymptomatic spread
      of hepatitis A.

PMID- 16951812
TI  - Erythrovirus B19 infection in acquired immunodeficiency syndrome: screening by
      histopathology, immunohistochemistry, and in situ hybridization.
AB  - Erythrovirus B19 infects erythrocytic progenitors, transiently interrupting
      erythropoiesis. In AIDS patients it causes chronic anemia amenable to treatment.
      We looked for evidences of B19 infection in stored bone marrow material from
      patients with acquired immunodeficiency syndrome. Histological sections were made
      from stored paraffin blocks from 33 autopsies (39 blocks) and 35 biopsies (45
      blocks, 30 patients) performed from 1988 to 2002. They were examined after
      hematoxylin-eosin (HE) staining, immunohistochemical (IHC), and in situ
      hybridization. HE revealed intra-nuclear inclusion bodies ("lantern cells")
      suggesting B19 infection in 19 sections corresponding to 19 of 63 patients
      examined with this test. Seven of 78 sections subjected to immunohistochemistry
      were positive, corresponding to 7 of 58 patients examined with this test.
      Fourteen sections corresponding to 13 of the 20 HE and/or IHC positive patients
      were subjected to in situ hybridization, with six positives results. Among the 13
      patients subjected to the three techniques, only one gave unequivocal positive
      results in all and was considered a true positive. The frequency of B19 infection
      (1/63 patients) in the material examined can be deemed low.

PMID- 16951813
TI  - Clinical outcome and risk factors related to extended-spectrum beta-lactamase
      producing Klebsiella spp. infection among hospitalized patients.
AB  - Over the past two decades, nosocomial infections caused by extended-spectrum beta
      lactamase (ESBL)-producing Klebsiella spp. have become a major problem all around
      the world. This situation is of concern because there are limited antimicrobial
      options to treat patients infected with these pathogens, and also because this
      kind of resistance can spread to a wide variety of Gram-negative bacilli. Our
      objectives were to evaluate among in-patients at a public university tertiary
      care hospital with documented infection due to Klebsiella spp., which were the
      risk factors (cross-sectional analysis) and the clinical impact (prospective
      cohort) associated with an ESBL-producing strain. Study subjects were all
      patients admitted at the study hospital between April 2002 and October 2003, with
      a clinically and microbiologically confirmed infection caused by Klebsiella spp.
      at any body site, except infections restricted to the urinary tract. Of the 104
      patients studied, 47 were infected with an ESBL-producing strain and 57 with a
      non-ESBL-producing strain. Independent risk factors associated with infection
      with an ESBL-producing strain were young age, exposure to mechanical ventilation,
      central venous catheter, use of any antimicrobial agent, and particularly use of
      a 4th generation cephalosporin or a quinolone. Length of stay was significant
      longer for patients infected with ESBL-producing strains than for those infected
      with non-ESBL-producing strains, although fatality rate was not significantly
      affected by ESBL-production in this cohort. In fact, mechanical ventilation and
      bacteremia were the only variables within dependent association with death
      detected in this investigation.

PMID- 16951814
TI  - Prevalence of hepatitis A virus infection in Goiania, Goias, Brazil, by molecular
      and serological procedures, 1995-2002.
AB  - In this study, a total of 865 serum samples were collected between 1995 and 2002
      from individuals living in Goiania, Central Brazil, and clinically suspected of
      hepatitis. After exclusion of 162 samples which were positive for hepatitis B
      virus or hepatitis C virus, 703 samples were tested for anti-hepatitis A virus
      (anti-HAV) IgM antibodies by enzyme immunoassay. In addition, 588 of these
      samples and 22 fecal samples were analyzed by reverse transcription-nested PCR
      for HAV RNA detection, with positivity indices of 13.1% (77/588) and 54.5%
      (12/22), respectively. A similar index of viral RNA detection in anti-HAV-IgM
      positive or negative samples was observed in serum samples. HAV infection is a
      public health problem worldwide and this study underscores the extent of HAV
      circulation in our region.

PMID- 16951815
TI  - Polymerase chain reaction with lesion scrapping for the diagnosis of human
      American tegumentary leishmaniasis.
AB  - The objective of this work was to compare the polymerase chain reaction (PCR)
      using lesion scrapping with other conventional techniques for the diagnosis of
      the American tegumentary leishmaniasis (ATL). For this, patients with cutaneous
      lesions suspected to be ATL were studied. The DNA was amplified with the
      MP1L/MP3H primers. From the 156 studied patients, 79 (50.6%) presented positive
      parasite direct search (PD), 81 (51.9%) had positive Montenegro skin test (MST),
      and 90 (57.7%) presented PD and/or MST positive. The PCR was positive in all of
      the positive-PD patients (100% sensitivity), in 91.1% of the positive PD and/or
      MST patients, and in 27.3% of the patients that presented negative PD and
      positive MST. The PCR positivity was similar to the PD (P = 0.2482) and inferior
      to the MST (P = 0.0455), and to the PD/MST association (P = 0.0133). The high PCR
      sensitivity, and positivity in those cases where the PD was negative, highlights
      the importance of this technique as an auxiliary tool for the diagnosis of ATL.

PMID- 16951816
TI  - Anatomical studies of sibling species within neotropical lymnaeids, snail
      intermediate hosts of fascioliasis.
AB  - Several anatomical parameters of the reproductive system have been used to
      distinguish Lymnaea cubensis from L. viatrix, the snail hosts of fascioliasis in
      South America and the Caribbean area. Three samples have been collected in the
      type localities of L. cubensis (Cuba), L. viatrix var. A ventricosa (Argentina,
      Rio Negro Lower Valley), and L. viatrix var. B elongata (Peru, Lima),
      respectively. Only one parameter, the relative lengths of the penis sheath and
      preputium, showed significant differences between L. viatrix var. ventricosa and
      the two other taxa. None of the studied parameters separated L. cubensis from L.
      viatrix var. elongata.

PMID- 16951817
TI  - Activated peripheral lymphocytes with increased expression of cell adhesion
      molecules and cytotoxic markers are associated with dengue fever disease.
AB  - The immune mechanisms involved in dengue fever and dengue hemorrhagic/dengue
      shock syndrome are not well understood. The ex vivo activation status of immune
      cells during the dengue disease in patients was examined. CD4 and CD8 T cells
      were reduced during the acute phase. Interestingly, CD8 T cells co-expressing
      activation marker HLA-DR, Q, P, and cytolytic granule protein-Tia-1 were
      significantly higher in dengue patients than in controls. Detection of adhesion
      molecules indicated that in dengue patients the majority of T cells (CD4 and CD8)
      express the activation/memory phenotype, characterized as CD44HIGH and lack the
      expression of the naive cell marker, CD62L LOW. Also, the levels of T cells co
      expressing ICAM-1 (CD54), VLA-4, and LFA-1 (CD11a) were significantly increased.
      CD8 T lymphocytes expressed predominantly low levels of anti-apoptotic molecule
      Bcl-2 in the acute phase, possibly leading to the exhibition of a phenotype of
      activated/effector cells. Circulating levels of IL-18, TGF-b1 and sICAM-1 were
      significantly elevated in dengue patients. Early activation events occur during
      acute dengue infection which might contribute to viral clearance. Differences in
      expression of adhesion molecules among CD4 and CD8 T cells might underlie the
      selective extravasation of these subsets from blood circulation into lymphoid
      organs and/or tissues. In addition, activated CD8 T cells would be more
      susceptible to apoptosis as shown by the alteration in Bcl-2 expression.
      Cytokines such as IL-18, TGF-b1, and sICAM-1 may be contributing by either
      stimulating or suppressing the adaptative immune response, during dengue
      infection, thereby perhaps establishing a relationship with disease severity.

PMID- 16951818
TI  - Isolation of respiratory syncytial virus from nasopharyngeal aspirates stored at
      20 degrees C from one to fifteen months after collection.
AB  - Cell culture isolation is used for recovering respiratory syncytial virus (RSV)
      from respiratory specimens. As RSV is a thermolabile virus, specimens destined
      for inoculation into cell culture require special transport, handling, and
      storage. The isolation rate of RSV from nasopharyngeal aspirates (NPA) stored at
      20 20 degrees C for one to 15 months after collection was investigated. A total
      of 126 samples considered positive for RSV by indirect fluorescence-antibody were
      tested by virus isolation in HEp-2 cell culture. RSV was isolated from 47/126
      specimens (37.3%). These results show that RSV may be recovered from NPA stored
      at 20 20 degrees C by cell culture.

PMID- 16951819
TI  - Molecular characterization of human Trypanosoma cruzi isolates from endemic areas
      in Panama.
AB  - The present work provides information on Trypanosoma cruzi genotype circulating
      in endemic areas of Chagas disease in Panama. A total of 26 crude stocks of T.
      cruzi, isolated from the blood of persons with different clinical profiles of
      Chagas disease were collected and crio-conserved until used. Most of the stocks
      had been characterized by means of isoenzyme electrophoresis on cellulose acetate
      membranes. The clinical profiles of infected persons included 9 (34.6%)
      asymptomatic and 17 acute (65.4%) including 5 (19.2%) fatal cases, 2 under 5
      years old and 3 adults. A multiplex-PCR assay based on the amplification of the
      non-transcribed spacer of the mini-exon gene was performed. All stocks of T.
      cruzi included in the study were found to correspond to Tc I group. This result
      supports the predominance of T. cruzi-I in the transmission cycles affecting the
      human population in the Republic of Panama.

PMID- 16951820
TI  - Diphtheria-neutralizing antibody levels in healthy adults from Rio de Janeiro,
      Brazil.
AB  - In Brazil, until 2004, the immunization policy against diphtheria involved
      childhood vaccination with no official routine booster dose administered after 15
      years of age. This study assessed functional antibody levels against diphtheria
      among blood donors. A total of 140 blood samples were collected, and diphtheria
      antitoxin levels were evaluated by Vero cell neutralization test. The mean age of
      the population was 34 years old (range: 18-61 years); 37.8% females and 62.2%
      males. Overall, 30.7% (95%, CI: 23.4-38.7) individuals presented neutralizing
      antitoxin antibody titers < 0.01 IU/ml; 42.1% (95%, CI: 34.1-50.4) showed values
      between 0.01-0.09 IU/ml and, 27.1% (95%, CI: 20.2-34.9) had (3) 0.1 IU/ml. In the
      subgroup of individuals with history of diphtheria immunization during childhood
      (85%), a number of 28.5% showed unprotective levels of circulating neutralizing
      antibody (< 0.01 IU/ml). Despite the continuous progress of immunization programs
      directed to Brazilian population, currently healthy adults remain susceptible to
      diphtheria.

PMID- 16951821
TI  - [Bone marrow cells and cardiac repair].

PMID- 16951822
TI  - [Natriuretic peptides as prognosticators in congestive heart failure].

PMID- 16951823
TI  - [The Portuguese version, cross-cultural adaptation and validation of specific
      quality-of-life questionnaire -AQUAREL - for pacemaker patients].
AB  - OBJECTIVE: To translate, to make the cultural adaptation and to evaluate
      reproducibility and validity of the Portuguese version of the AQUAREL (Assessment
      of QUAlity of life and RELated events) questionnaire, which is a specific tool to
      assess quality of life in pacemaker patients. METHODS: We evaluated 202 pacemaker
      patients: 63 patients during the cross-cultural adaptation stage and 139 during
      the reproducibility and validity evaluation stages. The questionnaire translation
      was reviewed repeatedly until > or = 85% of patients correctly understood the
      questions. Reproducibility of the final version was tested in 69 patients in whom
      the interview was performed twice by the same researcher. Validity was checked by
      the correlation between scores obtained in AQUAREL domains and those obtained in
      SF36 domains, in the functional class and the distance walked in the six-minute
      test. RESULTS: The internal consistency of AQUAREL was adequate, with Cronbachs
      alpha coefficient varying between 0.59 and 0.85. Reproducibility was good, with
      high correlation coefficients (0.68-0.89) and random distribution of data in
      Bland and Altman plots, without systematic bias. A significant association was
      observed among AQUAREL domains and those obtained in SF36 domains and the
      functional class (p<0.01), although significant correlations with the distance
      walked in the six-minute test were not found. CONCLUSION: The Portuguese version
      of the AQUAREL questionnaire is easy and rapid to apply, and could be used as a
      specific questionnaire to assess quality of life in pacemaker patients.

PMID- 16951824
TI  - [Carotid intimal-medial thickening and endothelial function in coronary artery
      disease].
AB  - OBJECTIVE: To investigate the correlation between the endothelial function and
      the carotid intimal-medial thickening (IMT) in a population of patients with
      coronary artery disease, as well as that between the endothelial function and
      carotid IMT with the severity of the coronary lesions. METHODS: Forty-three
      patients aged 60.5+/-9.2 years, (67.4% males) with coronary artery disease at the
      coronariography were studied. Endothelial function was assessed using the
      brachial artery reactivity test (BART), which measured the percentage of flow
      mediated dilatation (%FMD). The carotid IMT was evaluated through vascular
      ultrasound. RESULTS: The mean %FDM was 4.7 +/- 3.6 and the mean carotid IMT was
      1.08 +/- 0.23 mm. The carotid MIT and %FMD measurements showed a statistically
      significant correlation, with Spearmans coefficient of 0.315, p= 0.042,
      demonstrating that lower %FMD values corresponded to an increased carotid IMT (r
      = -0.315, p = 0.042). There was no correlation between %FMD or IMT and the
      severity of coronary lesions. CONCLUSIONS: The presence of a correlation between
      carotid IMT and %FMD demonstrates a concomitance of anatomical and functional
      vascular alterations in coronary artery disease, regardless of the severity of
      the atherosclerotic lesions.

PMID- 16951826
TI  - [Angiographic geometric predictors of myocardial infarction are not associated
      with ultrasonographic markers of plaque vulnerability].
AB  - OBJECTIVE: Some angiographic geometric features of coronary lesions have recently
      been described as independent predictors of myocardial infarction. The purpose of
      this study was to correlate these geometric markers with intravascular ultrasound
      findings known to be associated with greater vulnerability to plaque rupture.
      METHODS: A total of 30 patients with stable coronary syndromes and de novo
      lesions (31 lesions) underwent coronary angiography and intravascular ultrasound
      (IVUS). For each lesion, angiographic geometric features (degree of symmetry,
      degree of stenosis, lesion length, and outflow angle) were correlated with the
      following ultrasound variables: type of plaque (soft, fibrous, mixed, or
      calcified), plaque burden and remodeling index. RESULTS: Mean lesion length was
      9.2 +/- 4.4 mm, percent stenosis was 50.0% to 89.0% (mean 67.7 +/- 12.1%), inflow
      angles ranged from 8.48 degrees to 48.78 degrees (mean 24.0 +/- 11.4 degrees),
      outflow angles ranged from 8.30 degrees to 53.03 degrees (mean 23.8 +/- 11.7
      degrees), and the symmetry index ranged from 0 to 1 (mean 0.56 +/- 0.32). On
      ultrasound evaluation, frequency of soft or calcified plaques, positive
      remodeling, and magnitude of plaque burden were not associated with any
      angiographic geometric feature (p > 0.05 for all analysis). CONCLUSION:
      Angiographic geometric features that predispose to acute occlusion do not
      correlate with IVUS morphologic and quantitative findings associated with plaque
      vulnerability.

PMID- 16951825
TI  - [QT interval dispersion analysis in acute myocardial infarction patients:
      coronary reperfusion effect].
AB  - OBJECTIVE: To study the effect of early reperfusion of infarct-related artery on
      QT(DeltaQT) dispersion interval, as well as how valuable it is as a marker for
      coronary reperfusion and ventricular arrhythmias. METHODS: One hundred and six
      patients with reperfusion (WR) and 48 without reperfusion (WtR) who have received
      thrombolytic therapy in the acute phase of infarction were studied. ECG carried
      out on admission as well as on day 4 of patients course were analyzed. DeltaQT -
      defined as the difference between maximum and minimum QT interval - was measured
      by 12-lead ECG. RESULTS: The reperfusion group showed significant DeltaQT
      reduction - from 89.66+/-20.47ms down to 70.95+/-21.65ms (p<0.001). On the other
      hand, the group without reperfusion showed DeltaQT significant increase - from
      81.27+/-20.52ms up to 91.85+/-24.66ms (p<0.001). Logistic regression analysis
      showed that reduction magnitude between pre- and post-thrombolysis DeltaQT was
      the independent factor to most effectively identify coronary reperfusion (OR
      1.045, p<0.0001; CI 95%). No significant difference was found in dispersion
      measures when patients with ventricular arrhythmias were compared with those with
      no arrhythmias in the course of the first 48 hours. CONCLUSION: The study shows
      that DeltaQT is significantly reduced in patients with acute myocardial
      infarction submitted to successful thrombolysis, and is increased in infarcted
      patients with closed artery. DeltaQT reduction between the pre- and post
      thrombolysis condition was a predictor for coronary reperfusion of those
      patients, and did not show correlation to ventricular arrhythmias.

PMID- 16951827
TI  - [Analysis of electrocardiographic recordings associated with acute myocardial
      infarction].
AB  - OBJECTIVE: Evaluate correlations between variations in eletrocardiogram (ECG)
      recordings and acute myocardial infarction. METHODS: Use of a low-cost software
      to digitalize printed and/or ".pdf" file format ECG recordings. Calculation of ST
      segment area and amplitudes of the J and Y points. RESULTS: The amplitude of the
      Y point holds maximum correlation with troponin concentration. ST-segment
      elevation is not a good statistical indicator of myocardial infarction severity.
      There is a strong negative correlation between the amplitude of the J point and
      the amount of magnesium ions, but no statistical correlation with sodium or
      calcium ions. Neither method for calculating the ST-segment area (pixel counts
      and interpolation) indicated any significant differences in the results.
      CONCLUSION: The software used proved to be functional and cost-effective. Y point
      amplitude is a sensitive marker of myocardial infarction, and is also a
      calculation method both simpler to use and less subject to error than the
      calculation of the ST-segment elevation area.

PMID- 16951828
TI  - [Aortic stenosis and coronary disease. Analysis of risk factors].
AB  - OBJECTIVE: To analyze clinical laboratorial aspects of the presence of coronary
      disease in patients with aortic stenosis and evaluate the influence of risk
      factors in the development of obstructive coronary disease. METHODS: We studied
      65 patients who had severe aortic stenosis with an indication for surgery, ages
      51 to 85 years, 40 of them women. The coronary angiography assessment resulted in
      two groups: 26 (40%) with obstructive coronary disease and 39 (60%) with no
      coronary artery lesion. Personal antecedents for coronary disease (smoking,
      dyslipidemia, diabetes mellitus, arterial hypertension, family antecedents,
      sedentarism, and alcoholism) were analyzed. Additionally, the following
      assessments were made: electrocardiogram, echocardiogram with Doppler, and
      laboratory tests (blood glucose, total cholesterol and fractions, triglycerides,
      Apo-A1 and B, fibrinogen, lipoprotein (a) and fraction of triglycerides and
      cholesterol removal in both groups. RESULTS: In the age analysis, the group with
      obstructive coronary disease belonged to an older age range with statistical
      significance (p<0.0001). Signs of ischemia of the anterior wall identified on the
      electrocardiogram showed a significant relationship with the obstruction of an
      anterior interventricular artery (p<0.002). The univariate analysis showed a
      significant difference between the groups regarding averages of the aortic (p=
      0.041), HDL (p=0.042), and fibrinogen (p=0.047) gradients. The group with
      coronary disease presented an average gradient and HDL level lower than the group
      without obstructive coronary disease. For the fibrinogen variable, the average in
      the group with no coronary disease was lower compared to that of the
      coronariopathy group. The multivariate logistic regression analysis showed
      fibrinogen levels as an independent variable for coronary disease (p<0.039).
      CONCLUSION: Fibrinogen was an independent risk factor for the association between
      obstructive coronary disease and aortic stenosis.

PMID- 16951829
TI  - [Assessment of left ventricular diastolic function in hypertensive patients under
      different hemodynamic conditions: comparative study between transmitral and
      tissue Doppler echocardiography].
AB  - OBJECTIVE: To evaluate the behavior of LV diastolic displacement velocities of
      basal posterior septum near mitral ring segment obtained by tissue Doppler in
      relation to mitral flow velocities of hypertensive subjects, submitted to preload
      increase by left inferior limbs elevation for 5 minutes, and during 1 minute of
      handgrip (conditions 1 and 2, respectively). METHODS: Twenty five outpatients (15
      men, 52+/-11 years), with arterial hypertension > 3 years, by the transmitral
      flow Doppler variables: E, A and E/A, and of tissue Doppler: E', A' and E'/A', in
      basal situation and in conditions 1 and 2. For comparison of results in basal
      situation with conditions 1 and 2 a paired t test was applied. RESULTS: E(cm/s)
      varied from 68,88 +/- 11,94 to 75,82 +/- 15,71* and E'(cm/s) varied from 8,22 +/-
      2,30 to 8,31 +/- 2,24 in condition 1 (p<0.05). In addition, a comparison of
      variation percent (%) of Doppler transmitral indices with corresponding tissue
      Doppler indices variation % showed a significant difference between E and E',
      with preload increase (p=0.01). CONCLUSION: Patients with left ventricular
      adaptation to systemic arterial hypertension showed less modification of the
      index E' than E, after preload increase maneuver, an evidence that may suggest
      its more ample utilization in the context of echocardiographic left ventricular
      diastolic function evaluation.

PMID- 16951830
TI  - [Vascular reactivity response to mental stress in pregnant women with mitral
      stenosis].
AB  - OBJECTIVE: To study vascular reactivity according to the analysis of blood flow
      and peripheral vascular resistance at rest and during mental stress in pregnant
      women with mitral stenosis. METHODS: Twenty two women with mitral stenosis, 13 of
      whom were pregnant (PS) and 9 were non-pregnant (MIS), and 9 healthy pregnant
      women (NP) were studied. During gestation, 9 out of the 13 patients of the PS
      group required a beta-blocker (PSB) and the remaining 4 progressed without
      medication (PSWB). Plethysmography at rest and during mental stress analyzed
      muscle blood flow, peripheral vascular resistance (PVR), mean arterial pressure
      (MAP) and heart rate (HR) during gestation and puerperium. RESULTS: During
      gestation of PSWB, muscle blood flow and HR were higher in 1.6% and 20.5% (p =
      0.05), and PVR and MAP were lower in 19.3% and 4.4%, respectively, in comparison
      to the puerperium; during mental stress, the muscle blood flow increased by
      55.9%, HR decreased by 30.2% and PVR and MAP were similar. In PSB, muscle blood
      muscle blood flow and HR were greater in 5.9% and 14.9% (p= 0.001) and MAP and
      PVR were lower in 10.3% and 9.1%, respectively, when compared to the puerperium.
      During mental stress, muscle blood flow and MAP increased by 69.8% and 174.1%,
      respectively. HR was similar and PVR decreased by 53.7%. The comparative study
      showed that in the NP group the muscle blood flow was higher, PVR was lower, and
      MAP and HR were similar in relation to the PS group, and that the PS, NP, MIS
      groups had a similar response to mental stress. CONCLUSIONS: Vascular reactivity
      in pregnant women with mitral stenosis was preserved and the analysis of
      measurements showed lower values of muscle blood flow and higher values of PVR
      when compared to those of healthy pregnant women.

PMID- 16951831
TI  - [Maximal workload prediction models in the clinical cardio-pulmonary effort
      test].
AB  - OBJECTIVE: This study sought to derive generalized equations for predicting
      maximal workload for young men and women. METHODS: Direct ergospirometry
      (Aerosport TEEM 100, USA) was used to determine VO2max and the maximal work load
      (Wmax) on the cycle ergometer test (Monark,Brazil) of thirty men (25 +/- 5 years,
      75.0 +/- 10.7 kg; 48.4 +/- 8.8 mL x kg(-1) x min(-1) and 243 +/- 51 Watts) and
      thirty women (26 +/- 5 years, 56.7 +/- 5.9 kg, 39.8 +/- 7.6 mL x kg(-1) x min(-1)
      and 172 +/- 37 Watts). Age and body mass were used as independent variables. For
      all statistic tests, a p < 0.05 significance level was adopted. RESULTS: In the
      multiple linear adjustment, the maximal workload was explained by age and body
      mass as 54% (r = 0.73) for men, and as 76% (r = 0.87) for women, with standard
      errors of 0.66 W x kg(-1) and 25 Watts. The proposed equations were cross
      validated using another sample with similar age and VO2max characteristics
      comprised of fifteen men and fifteen women. The intraclass correlation between
      the predicted Wmax values and those measures by ergospirometry were 0.70 and
      0.69, with standard errors of 28.4 and 15.8 Watts, respectively, for men and
      women. CONCLUSIONS: This study exhibits valid generalized equations for
      determining the maximal cycle ergonometer workload for men and women.

PMID- 16951832
TI  - [Prognosis of Duke treadmill score versus scintilography in patients at risk for
      coronary artery disease. One year follow-up].
AB  - OBJECTIVE: The purpose was to determine the sensitivity, the specificity and a
      year-long risk of subsequent cardiovascular events in patients with low,
      intermediate and high risk prognostic Duke treadmill score (DTS) in comparison
      with the presence (or not) of the myocardial perfusion defects on radionuclide
      images. METHODS: A prospective study, with 173 consecutive patients with 02 or
      more risk factors to coronary artery disease (CAD), who underwent to exercise
      single photon - emission computed tomographic myocardial perfusion images using
      technetium-99m tetrophosmin (SPECT) and treadmill test (with DTS), from one
      neighbourhood of Curitiba city, between January 2003 and February 2004, were
      followed up for cardiac-cause mortality and major cardiac events. Follow-up was
      performed in 13+/- 1 months and in 162 patients was complete. RESULTS: The DTS
      mean those patients with cardiac event (18) over a year was -0.27 (95% CI= -3.97
      to +3.91) and those free cardiac event patients (144) was +4.92 (95% CI= +4.03 to
      +5.81), with p<0.00069. The DTS sensitivity was 72.22% and the SPECT sensitivity
      was 77.78%, with no significant difference p=0.21. The DTS specificity was 54.17%
      and the SPECT specificity was 88.19%, with p<0.0001. The cumulative proportion
      free-events (Kaplan-Meier) curves demonstrated that 94% those patients with low
      risk DTS remained free-cardiac events. In contrast, all high-risk DTS had adverse
      cardiac events. Those patients with intermediate-risk DTS had 15% of cardiac
      event over a year. CONCLUSIONS: The DTS was as sensitivity as SPECT in determine
      a year risk for CAD. Those patients with DTS <-0.27 had high-risk cardiac event.

PMID- 16951833
TI  - [Relationship between waist circumference and nutritional status, lipid profile
      and blood pressure in low socioeconomic level pre-school children].
AB  - OBJECTIVE: To evaluate anthropometric data, blood lipid levels, blood pressure
      (BP) and waist circumference (WC) in preschool children. To relate WC with blood
      lipid levels and BP in obese and non-obese children. METHODS: In a transversal
      study we investigated 65 preschool children of low socioeconomic level in Santo
      Andre, Sao Paulo. The evaluation consisted of BP measurement (Task Force, 1996),
      weight (W), height (H) expressed as z score (WHO, 1995) and body mass index
      (BMI), triglycerides, total and fractions of cholesterol blood levels
      (Kwiterovich and AHA). STATISTICAL ANALYSIS: Fisher test and correlations.
      RESULTS: We observed high BP and lipid levels unrelated to nutritional status. WC
      was significantly and positively correlated to BMI and ZWH (r = 0.87 and r =
      0.83, respectively). Using as a cut-off 75 percentile of WC we found an accuracy
      of 89.1% with 87.2% specificity and 70.6% sensitivity and predictive value (+)
      66.7% and (-) 66.7%. There was no relationship between WC and lipid and BP
      levels. CONCLUSIONS: WC showed direct correlation with anthropometric indexes
      commonly used and in preschool children wasn't predictor of cardiovascular risk.

PMID- 16951834
TI  - [Early results of bone marrow cell transplantation to the myocardium of patients
      with heart failure due to Chagas disease].
AB  - OBJECTIVE: To evaluate early effects of bone marrow cell transplantation to the
      myocardium of patients with heart failure (CHF) due to Chagas disease. METHODS:
      We studied 28 patients (mean age 52.2 +/- 9.9), of whom 24 were male. Despite
      optimized treatment, 25 patients were in NYHA class III and three patients, in
      NYHA class IV. The procedure consisted of aspiration of 50 mL of bone marrow,
      separation of the mononuclear fraction, and intracoronary injection. Effects on
      left ventricle ejection fraction (LVEF), distance walked in the six-minute
      walking test, quality-of-life, NYHA class, arrhythmogenic and biochemical
      parameters, were all evaluated. RESULTS: There were no complications directly
      related to the procedure. Baseline left ventricular ejection fraction was 20.1 +/
      6.8%, and 60 days after transplantation it increased to 23.0 +/- 9.0%, p = 0.02.
      Significant improvements were observed in the NYHA class (3.1 +/- 0.3 to 1.8 +/-
      0.5; p < 0.0001); quality-of-life (50.9 +/- 11.7 to 21.8 +/- 13.4; p < 0.0001);
      and distance walked in six minutes (355 +/- 136 m to 443 +/- 110 m; p = 0,003).
      The number of ventricular premature beats in 24 hours tended to increase (5,322
      +/- 4,977 to 7,441 +/- 7,955; p = 0,062), but without increase in ventricular
      tachycardia episodes (61 +/- 127 to 54 +/- 127; p = 0.27). CONCLUSION: Our data
      demonstrate for the first time that intracoronary injection of bone marrow
      mononuclear cells is feasible and suggest that it may be potentially safe and
      effective in patients with CHF due to Chagas disease.

PMID- 16951835
TI  - [Perceptions of heart failure diagnosis and management: comparison between
      clinical cardiologists and family doctors].
AB  - OBJECTIVE: To compare the perceptions of heart failure (HF) diagnosis and
      management between clinical cardiologists (CC) and family doctors (FD) in the
      city of Niteroi. METHODS: A qualitative questionnaire, validated by the EURO-HF
      study, was submitted to 54 FD and 62 CC. These professionals supplied the
      following information: HF diagnosis; availability of complementary tests; which
      tests were used more often; names, dosages and adverse effects of the medications
      prescribed; and which pharmaceuticals reduced mortality. RESULTS: FD and CC
      reported that the most common signs and symptoms identified by HF patients were:
      dyspnea, edema and fatigue (96.3% vs. 100%, 74% vs. 58% and 22.2% vs. 67.7%). The
      HF classification method used most often by FD was mild/moderate/severe (53.8%)
      while the CC used the NYHA method (72.7%) more often. CC request echocardiograms
      more often than FD (p < 0.001). CC differentiate HF with preserved systolic
      function from HF with systolic dysfunction more often than FD (p < 0.001). CC use
      beta-blockers (p < 0.001), angiotensin-converting enzyme inhibitors (p < 0.001)
      and spironolactone (p < 0.001) more often than FD. The angiotensin-converting
      enzyme (ACE) inhibitor dosages used by CC are greater than those used by FD (p <
      0.001) and the spironolactone dosages used by CC are closer to those recommended
      in medical literature. CONCLUSION: CC use a more intensive investigative
      diagnosis and medications that are more effective in reducing morbidity and
      mortality rates for HF patients.

PMID- 16951836
TI  - [Serum NT-proBNP levels are a prognostic predictor in patients with advanced
      heart failure].
AB  - OBJECTIVE: To verify if the determination of NT-proBNP values would help predict
      the prognosis in advanced heart failure (HF) patients. METHODS: One hundred and
      five subjects with average age of 52.4 years were evaluated, 66.6% of them males.
      Thirty-three (32.0%) subjects were outpatients and 70 (67.9%) were inpatients
      (functional class III/IV) admitted to the hospital for cardiac compensation. All
      patients had left ventricular systolic dysfunction and a mean ejection fraction
      of 0.29. The NT-proBNP levels were measured in all patients and they were
      followed-up over a period from 2 to 90 days (average 77 days). A ROC curve was
      drawn to determine the best cut-off point, as well as the corresponding Kaplan
      Meyer survival curves. RESULTS: During the follow-up period, 22 patients died.
      The average NT-proBNP value of the patients who remained alive was 6,443.67+/
      6,071.62 pg/ml, whereas that of those who died was 14,609.66+/-12,165.15 pg/ml
      (p=0.001). The ROC curve identified a cut-off point at 6,000 pg/ml with 77.3%
      sensitivity (area under the curve: 0.74). The survival curve for values below and
      above 6,000 pg/ml was significantly different (p=0.002): patients with values
      below 6,000 pg/ml had a 90.2% 90-day survival, and those patients with values
      above, a 66% survival. CONCLUSION: Patients with advanced HF, especially those
      admitted to the hospital for cardiac compensation, had much higher NT-proBNP
      values, with a two-fold increase among those who died during the follow-up
      period. Values above 6,000 pg/ml identify the patients most likely to die within
      90 days after hospital discharge.

PMID- 16951837
TI  - [Score for nutritional status evaluation: the role played in the prognostic
      stratification of dilated cardiomyopathy and advanced heart failure patients].
AB  - OBJECTIVE: Develop a method for the evaluation of patients nutritional status
      through a score that expresses universal nutritional status, as well as
      investigate if that score would be efficient for the prognostic stratification of
      advanced heart failure (HF) pts. METHODS: The score was reached by the selection
      of evaluation methods that would quantify nutritional status: ideal body weight
      percentage, thickness of tricipital skinfold, percentiles for arm muscular mass
      circumference, albumin serum level, lymphocyte total count. In order to be
      validated, the score was applied to a group of 95 pts. Pts were under 65 years
      old no evidence of consumptive diseases. The score was analyzed to confirm
      whether it would keep correlation with HF clinical data and whether it would
      stratify its prognostic. RESULTS: Nutritional status suggesting moderate or
      severe malnutrition could be observed in 31/95 (32.6%). No correlation was found
      between nutritional score values and the duration of symptoms, or the level of
      ventricular dysfunction. Pts with high nutritional score showed a trend towards
      higher mortality rate (p=0.0606). CONCLUSION: Those data suggest malnutrition is
      reported by 1/3 of pts with advanced HF. A score comprising 5 parameters for
      nutritional status showed good correlation with the clinical, global evaluation
      of pts with HF. A score over 8 identified pts with higher probability of death as
      outcome, confirming that pts under higher malnutrition exhibit worse evolution.

PMID- 16951838
TI  - [Predictors of in-hospital lethality in patients with advanced heart failure].
AB  - OBJECTIVE: Describe the clinical characteristics and identify potential risk
      factors for in-hospital lethality in patients with decompensated heart failure
      admitted to an intensive care unit. METHODS: Decompensated heart failure patients
      consecutively admitted to an intensive care unit between June 2001 and December
      2003 were selected and followed during hospitalization until discharge or death.
      Clinical characteristics at admission were recorded and evaluated as independent
      risk predictors for in-hospital mortality by multiple logistic regression
      analysis. RESULTS: A total of 299 patients (69+/-13 years of age and 54% men)
      were enrolled. Coronary artery disease was the main cause of heart failure in 49%
      of the cases. Diabetes mellitus and systemic arterial hypertension occurred in
      37.5% and 78% of the patients, respectively. At admission, 22% of them had atrial
      fibrillation, 21.5% had renal dysfunction, and 48% anemia (16.5% with severe
      anemia). Severe systolic dysfunction (left ventricular ejection fraction <30%)
      affected 44% of the patients. In-hospital mortality was 17.4%. After the
      multivariate analysis had been performed, previous history of stroke, atrial
      fibrillation, renal failure, age > 70 years, and hyponatremia were independently
      associated with in-hospital mortality. CONCLUSION: Patients admitted to an
      intensive care unit due to decompensated heart failure have high in-hospital
      lethality. In this study, variables recorded at admission, such as previous
      stroke, atrial fibrillation, hyponatremia, renal failure, and age > 70 years were
      predictors of in-hospital lethality.

PMID- 16951839
TI  - [Percutaneous closure of atrial septal defect using transhepatic puncture].
AB  - The percutaneous closure of ostium secundum (OS) atrial septal defect (ASD) is a
      well-established procedure and is today considered the treatment of choice due to
      its good results and low morbidity and mortality. The procedure is routinely
      performed through the inferior vena cava (IVC). However, this route of access is
      not always available due to the obstruction or congenital absence of the IVC. We
      will present a case of ASD closure by means of transhepatic puncture due to the
      impossibility of using the IVC.

PMID- 16951840
TI  - [Contrast echocardiography. Does it have a future?].

PMID- 16951841
TI  - [Case 4/2006 - a 74 year-old woman presenting restrictive cardiomyopathy and
      cardiogenic shock].

PMID- 16951842
TI  - [Three-year-old child with subaortic stenosis, mitral stenosis due to parachute
      mitral valve, supravalvular mitral stenosis, coarctation of the aorta (Shone
      syndrome) associated with ventricular septal defect and ductus arteriosus].

PMID- 16951843
TI  - [Great arteries contribution in orthostasis cardiovascular adaptation].

PMID- 16951845
TI  - Postgraduate pariah.

PMID- 16951844
TI  - [II Brazilian guideline for severe heart disease].

PMID- 16951846
TI  - Experimental endolymphatic hydrops under action of a type II nitric oxide
      synthase inhibitor: otoacoustic emissions evaluation and electrocochleography.
AB  - In experimental endolymphatic hydrops distortion-products otoacoustic emission
      (dpoae) amplitudes decrease and there is elevation on electrocochleographic
      thresholds. Some authors found type ii nitric oxide synthase (nos ii) expression
      in hydropic cochleas and they suggest nitric oxide (no) may be involved in
      endolymphatic hydrops pathogenesis. The aim of this study was to evaluate the
      action of a nos ii inhibitor on dpoae and electrocochleography in experimental
      endolymphatic hydrops. MATERIAL AND METHODS: endolymphatic hydrops was induced in
      16 guinea pigs by obliterating the endolymphatic duct and sac in the right ear.
      They were divided in two groups: eigth guinea pigs under the action of
      aminoguanidine, a nos ii inhibitor and eigth control guinea pigs. We compared
      dpoae amplitudes at geometric means of frequencies 1062, 2187, 4375 and 7000 hz,
      compound action potential threshold at 1000, 2000, 4000 and 6000 hz and summating
      potential to action potential (sp/ap) ratio between the groups during the
      postoperative observation period of 16 weeks. RESULTS: there were no significant
      changes in the dpoae amplitudes and in the sp/ap ratio. The group that received
      aminoguanidine had a lower degree of threshold increase at 2000 (p<0.05) And 6000
      hz (p<0.05) In 12th postoperative week and at 1000 (p<0.05), 2000 (P<0.001), 4000
      (P<0.001) And 6000 hz (p<0.001) At 16th postoperative week. CONCLUSIONS: nos ii
      inhibitor decreased the electrocochleography threshold elevation on experimental
      endolymphatic hydrops.

PMID- 16951847
TI  - Midfacial degloving--access to nasal cavity and paranasal sinuses lesions.
AB  - Common surgical approaches for medial maxillectomy include lateral rhinotomy and
      midfacial degloving. Lateral rhinotomy provides excellent surgical exposure but
      leaves a bulging scar on the face. Despite its own limitations, midfacial
      degloving has been preferred to lateral rhinotomy because it does not leave any
      external scar on the face(1). The aim of this study is to evaluate the cosmetic
      results and surgical exposure access of midfacial degloving. Treatment morbidity
      was evaluated through: post operative hospital stay length, blood transfusion
      needs, complications, pre and post operative hemoglobin levels, disease
      recurrence, nasal packing, type of suture and antibiotics. Retrospective study
      was carried out with sixteen patients treated at the Hospital Geral de Fortaleza
      SESA/SUS from December 1999 through November 2003. Based on the results, we may
      conclude that midfacial degloving is effective to treat extensive nasal cavity
      lesions and paranasal sinuses with reduced post operative morbidity.

PMID- 16951848
TI  - Cephalometric study of alterations induced by maxillary slow expansion in adults.
AB  - Maxilla expansion is a procedure that aims at increasing the maxillary dental
      arch to correct occlusal disharmony. Largely used in children, its efficacy in
      adults, when craniofacial growth has attained bone maturity, is controversial.
      AIM: The present study has the objective of evaluating cephalometric
      modifications resulting from maxilla expansion in adult patients, observing the
      following linear measurements: facial width, nasal width, nasal height, maxillary
      width, mandibular width and maxillary molar width. MATERIAL AND METHODS: The
      sample was composed of 24 frontal teleradiographs, taken before and immediately
      after the expansions, from 12 male and female patients aged between 18 years and
      two months and 37 years and eight months. All patients were submitted to slow
      expansion of the maxillary bones by means of an appliance used in the technique
      named "dynamic and functional maxillary rehabilitation". Wilcoxon paired
      statistical test was used for related samples with a 5% significance level.
      RESULTS: There was a mean increase of 1.92 mm in nasal width and 2.5 mm in nasal
      height. As regards the linear measurements maxillary and mandibular width, the
      mean increase was 2.42 mm and 1.92 mm, respectively. A mean increase of 1.41 mm
      was found for facial width and 2.0 mm for maxillary molar width, alterations
      which were statistically significant, the mean time was 5.3 months. CONCLUSION:
      Based on the results obtained, it may be concluded that the use of maxillary
      expansion induces increase of the facial measurements studied in adults.

PMID- 16951849
TI  - Foreign body in ear, nose and oropharynx: experience from a tertiary hospital.
AB  - The occurrence of foreign bodies in otorhinolaryngology is reason of constant
      searches for emergency services. OBJECTIVE: To value the incidence of patients
      with foreign body, to analyze the clinical situation and the treatment in these
      cases. METHOD: The prospective study was realized in 81 patients with diagnosis
      of foreign body of nose, ear or oropharynx in the otorhinolaryngology service of
      the Hospital do Servidor Publico Municipal de Sao Paulo between april/2003 and
      march/2005. RESULTS: 57 cases of foreign body of ear, 13 cases of nose and 11 of
      oropharynx. These patients, 51.85% were men and 48.15% were women. The age
      average was 23 years old. The average of the evolution time was 18.36 days, being
      that 38.27% these cases were taken care in less 24 hours of evolution. Inside the
      total of patients, 83.95% received initial attendance in the otorhinolaryngology
      clinic, and 16.05% came of another service after some previous removal attempt.
      The most common symptom of the foreign bodies cases of oropharynx it was
      odinofagia present in 90.91% of the cases; in the foreign bodies of nose, the
      unilateral rhinorrhea and cacosmia were present in 46.15 of the cases; in the
      foreign bodies of ear, 38.60% evolved without symptoms and 28.07 with hipoacusia.
      The most frequent foreign body of oropharynx it was the fish spine (54.55%); in
      the nose it was the paper (30.77%); and in the ear it was the cotton (31.58%).
      The complications resulting of the presence of foreign body or about the
      manipulation of these had been found in 13 cases (16.05%). CONCLUSION: Most cases
      of foreign body conditions, in which a non-specialist professional or a non
      professional person previously handles its removal, have a bad evolution with
      emerging complications. Such outcomes strengthen the fact that an
      otorhinolaryngologist using the proper equipment must treat patients with foreign
      body.

PMID- 16951850
TI  - Acupuncture for tinnitus immediate relief.
AB  - The treatment of tinnitus, which is defined as conscientious perception of a
      sound originated in the ears or nervous system, represents until the current days
      a great challenge. The use of Acupuncture (ACP) is based on the stimulation with
      needles of specific points on the human anatomy. A prospective, randomized and
      double-blinded study was carried through in 76 patients taken care of in the
      Clinic of Tinnitus of the Department of Otorhinolaryngology and Head and Neck
      Surgery of the UNIFESP-EPM in the period understood between April and June of
      2005. All the patients had humming complaint and had been submitted to clinical
      anamnese, physical examination and subsidiary exams in order to investigate its
      etiology. The patients then were directed to a first researcher that determined
      an initial numeric value of the humming through Visual Analoge Scale(VAS),
      varying from 0 to 10 points. After this, had been directed for another room in
      which an acupuncturist doctor, who did not have access to the initial evaluation,
      separated the patients in Group Control and Group Study according to the
      attendance order, in alternating way. The ACP point used in patients of the Group
      Study places 6,5 cm above of the apex of the auditory pavilion in the parietal
      region. The point used in the Group Control places 3 cm above of the previous
      point, in the same vertical line. Then they had been sent back to the initial
      room for a new evaluation by the first researcher, where they had been guided to
      redefine the subjective score of the humming. Among the 76 studied patients, 29
      were male (38,2%) and 47 female (61,8%), with average age 56,9 + 12,0 years. The
      Groups Study and Control had counted on 38 patients each. Through the Anova test
      it was evidenced that it had significant difference (p<0,001) between the moments
      pre and post needling and that in the group Study this improvement is more
      evident (p=0,0127). The t-independent test showed that it had a significant
      difference (p=0,017) between the two moments in the groups Study and Control. We
      conclude that there was significant reduction of the counting of the moments pre
      and post needling in both the groups, and in the group study the reduction is
      greater that in the group control.

PMID- 16951851
TI  - Polisomnographic findings on children with laryngopathies.
AB  - Polysomnography is the goldstandard exam for child OSAS. When possible,
      polysomnography clearly distinguishes between those with isolated primary snoring
      and patients with sleep apnea (obstructive, central and mixed). The most common
      cause of OSAS in childhood is adenotonsillar hypertrophy. Laryngomalacia is the
      most common cause of stridor in childhood, though its physiopathology remains
      unknown. Among the most prominent theories are immaturity of the cartilaginous
      framework of the larynx and/or neuromuscular immaturity. OBJECTIVE: Our proposal
      was to describe polysomnographic findings in children with laryngomalacia or
      other isolated laryngeal alterations, that is, without other alterations in the
      upper airways. METHODS: The sample included 29 children with exclusively
      laryngeal alterations. All of them underwent an otorhinolaryngological exam,
      nasofibrolaryngoscopy and polysomnography. Information was recorded concerning
      age, nasofibrolaryngoscopy and polysomnography. For analysis, the children were
      divided into two groups: those with laryngomalacia and those with other laryngeal
      diseases. RESULTS: Among the 18 children with a diagnosis of laryngomalacia, 18
      had central breathing events, knowing that the majority had showed desaturation
      of oxihemoglobin and bradycardia. In this same group, 3 children had obstructive
      events. On the other hand, 11 children with other laryngeal alterations showed no
      predominance of one type or another of apnea. Of these, 4 had central type
      breathing events and 2 obstructive type. CONCLUSION: The majority of patients
      with laryngomalacia showed a central type apnea. Patients with various laryngeal
      diseases did not present a predominant type of apnea.

PMID- 16951852
TI  - Defect repair in rat mandible with hydroxyapatite cement compared to small
      intestine submucosa.
AB  - AIM: The aim of this study was to evaluate the bone formation in surgically
      created defects of rabbit mandibles by synthetic hydroxyapatite of calcium
      compared to small Intestine Submucosa. MATERIAL AND METHOD: 24 mice lineage
      Wisthar-Furth were used. A bony defect of 0,75 cm x 1,5 cm in mandibular ramus
      was accomplished in all animals. The hydroxyapatite implants were placed on the
      left hemimandiblein group I, small Intestine submucosa in group II, and the right
      served as control. The euthanasia was accomplished in the 40 degrees
      postoperative day, it was proceeded the macroscopic and histological analysis.
      RESULTS: medium length in millimeters of the hemimandibless in the hydroxyapatite
      group was of 3,75, in the small intestine submucosa 3,03 and the control group
      was of 2,63 (p: 0,022). Histomorphometry study revealed new bone grown in 76,64%
      of the total area in hydroxyapatite group (p: 0,022). In Small Intestinal
      submucosa group new bone grown in 63,64% do total (p: 0,0022). DISCUSSION:
      satisfactory bone integration was observed of the synthetic hydroxyapatite in
      that experimental model. Small intestinal submucosa cause osteoinduction
      CONCLUSION: using hydroxyapatite of calcium resulted in formation of
      significantly larger volume fractions of new bone when compared to small
      intestinal submucosa group.

PMID- 16951853
TI  - Surgery of frontal sinus fractures: epidemiologic study and evaluation of
      techniques.
AB  - The frontal sinus trauma is not rare and it is 8% of the facial fractures. It can
      affect the anterior and/or posterior plates, with or without hitting the
      nasofrontal duct. It has a large potential of complications and its management
      still being a controversy. OBJECTIVE: To present the casuistic of fractures
      frontal sinus, the epidemiology and clinical and surgical management of frontal
      sinus fractures. MATERIALS AND METHODS: Not randomized retrospective study of 24
      patients with frontal sinus fractures Hospital of Clinics, School of Medicine
      Botucatu, Sao Paulo, Brazil. RESULTS: From the 24 patients, we had 16 (66,6%)
      fractures of the extern plate and 8 (33,4%) of both. In 2 patients the
      nasofrontal duct was involved. Others facial fractures were associated in 20
      (83,4%) cases and major lesions of the cerebral segment were found in 13 (54,2%).
      Subpalpebral incision was performed in the majority with satisfactory aesthetic
      results. The basis of the surgical treatment was reduction and fixation with
      different materials (steel wire, mononylon, titanium miniplates) and if necessary
      we used alogen implants or parietal bone to reconstruct the anterior plate.
      CONCLUSION: The principal cause of frontal sinus fractures is crashed car. The
      management depends of the complexity, because commonly there are cranioencephalic
      lesions associated. The surgical techniques used are the incisions, bicoronal
      flap or brow-glabella, infra-orbital rim ("butterfly"), associated a endoscopy
      sinus surgery in cases of infection, cerebrospinal fluid leak and orbital
      complications.

PMID- 16951854
TI  - Effects of passive smoke inhalation on the vocal cords of rats.
AB  - Few studies have demonstrated the pathologic reactions yielded by smoke
      inhalation on the airway in rats. AIM: The aim of this study was to analyze the
      possible histopathological effects produced by chronic cigarette smoke inhalation
      on the vocal folds of rats. STUDY DESIGN: Experimental. MATERIAL AND METHOD: 36
      male rats (Rattus norvergicus Wistar strain), aged 60 days, were kept in cages
      and exposed to inhalation of the smoke produced by 10 cigarettes lit 3 times a
      day, 7 days a week, for periods of 25, 50 and 75 days, and their respective
      controls. Thereafter the animals were killed and their larynxes were dissected
      and submitted to histological processing for achievement of histological
      sections, which were stained with Hematoxylin and Eosin and analyzed by light
      microscopy. RESULTS: The rats exposed to smoke displayed smaller (p< 0,05) body
      mass than the control group. There was hyperplasia and squamous metaplasia in the
      free edge of the vocal fold and squamous hyperplasia on the middle portion of the
      vocal fold in all 3 study periods. Moreover, the 50-day group revealed
      keratinizing metaplasia in this area. Morphological alterations in other areas of
      the larynx and inflammatory reaction of the lamina propria were also not
      observed. CONCLUSION: It was concluded that the passive inhalation of cigarette
      smoke yields important morphological changes in the vocal fold epithelium, which
      may progress to neoplasia.

PMID- 16951855
TI  - Microbiology of the maxillary and ethmoid sinuses in patients with chronic
      rhinosinusitis submitted to functional endoscopic sinus surgery.
AB  - Chronic rhinosinusitis microbiology studies show the presence of aerobe and
      anaerobe microorganisms, fungus and virus and their incidence vary according to
      each study. These studies guide us on choosing the most adequate antimicrobial
      agent to eliminate the infectious process, thus, helping in restoring
      rhinosinusal mucosa. STUDY DESIGN: Clinical prospective. AIM: This work aimed at
      studying the microbiology of the maxillary and/or ethmoid sinuses of patients
      with chronic rhinosinusitis and with indication of functional endoscopic sinus
      surgery. MATERIALS AND METHODS: During surgery, we collected secretion and/or
      fragments of maxillary and/or ethmoid sinus mucosa from 41 patients to perform
      Gram stain, fungus direct research, aerobe and anaerobe microorganism culture and
      fungus culture. RESULTS: We identified the presence of aerobe microorganisms in
      21 patients (51.2%), anaerobe microorganisms in 16 (39%) and fungus in 1 (2.4%).
      In the studied population, only 12 patients (29.2%) presented microorganisms
      considered pathogenic when analyzed together with the semi-quantitative leukocyte
      count. Staphylococcus coagulase-negative and Staphylococcus aureus were the most
      frequent microorganisms found, in 5 (12.18%) and in 4 (9.75%) patients
      respectively. CONCLUSION: This study reveals that Staphylococcus coagulase
      negative and Staphylococcus aureus were the most frequent microorganisms isolated
      from patients with chronic rhinosinusitis.

PMID- 16951856
TI  - Contralateral suppression of otoacoustic emission in patients with tinnitus.
AB  - INTRODUCTION: The medial olivocochlear bundle effect is studied through the
      suppression of otoacoustic emissions and seems to be influenced by the laterality
      of the central nervous system, presenting no symmetry between right and left ear.
      A dysfunction of this bundle may be involved in the generation of tinnitus,
      although this fact was not confirmed. OBJECTIVES: Study the suppression of
      distortion product otoacoustic emissions in tinnitus patients. MATERIAL AND
      METHOD: A case-controlled study involving 44 tinnitus patients from the Tinnitus
      Group of the ENT Department of the University of Sao Paulo Medical School and 44
      controls who underwent distortion product otoacoustic emissions testing with and
      without contralateral noise. Only the results from the right ears from both
      groups were compared. RESULTS: There was a relationship between the presence of
      tinnitus and the absence of suppression at all frequencies studied (OR>2.1).
      CONCLUSION: There was a correlation between diminished effectiveness of the
      medial olivocochlear bundle and the presence of tinnitus.

PMID- 16951857
TI  - Auditory middle latency evoked responses: a standardizing study.
AB  - The presence of auditory middle latency evoked responses allows us to make an
      evaluation of the peripheral and central auditory system integrity , as well as
      the nucleus and auditory ways existing until the level of the thalamus-cortical
      region and primary auditory cortex. AIM: Our objective is to evaluate the
      presence or not of this numerous peaks, as well as, their latencies and intervals
      and extend to make a standardizing study. WAY OF STUDY: Contemporary study of
      Coorte with transversal cut and the outline was quantitative, descriptive e non
      experimental. MATERIAL AND METHOD: Studying several peaks, positives and
      negatives, caused by the middle latency auditory potentials, in a population of
      young adults individuals, ranging from 18 to 30 years old, from both genders,
      with normal hearing. It was used a monoauricular resonant stimulation and a
      capitation, separately, in both cerebral hemispheres, with surface electrodes.
      RESULTS: In this research was verified that the analyzed crossings did not
      present statistically significant results and it was stipulated a pattern from
      the obtained results. Based on the non-statistical difference found we can affirm
      that to the Po waves was obtained respectively an average and standard deviation
      of 12,09 and 1,84; for Na 17,91 and 2,60; for Pa 29,41 and 5,66; for Nb 41,43 and
      8,89; to for 51,44 ms e 12,63 and finally to the interval Na-Pa 11,52 and 4,99.
      CONCLUSION: 1- The presence of the defluxions Po, Na, and Pa was verified in all
      the registers, whereas the defluxions Nb and Pb were absent in only 06 registers.
      2- By having these registers, we evaluated that the inveiglement of these
      defluxions can be used as a reliable method to detect the average latency of the
      auditory potentials, by electrical generated activities, possibly in sites
      located in the thalamus-cortical area, evoked by sonorous stimulation. From that
      point, we establish a pattern of responses for young ones with normal hearing,
      helping us with future studies in patients with alterations in the hearing
      system.

PMID- 16951858
TI  - Etiology and incidence facial fractures in children and adults.
AB  - Facial trauma has presented an increasing occurrence in the last four decades,
      due especially to the growth of accidents with automobiles as well as to the
      urban violence. Both of which continue being the main cause of such traumas. AIM:
      To evaluate the features of the population victim of facial trauma as to gender,
      age, occupation, origin, type of fracture and its cause. DESIGN STUDY:
      retrospective clinical with transversal cohort. MATERIAL AND METHOD:
      Retrospective study consulting hospital registers of 513 patients victims of the
      facial trauma. RESULTS: There was a higher incidence of facial trauma on men
      (84,9%), white (82,7) and with an average age of 29. Regarding occupation, the
      trauma was mostly occurred to students (16,6%) and Masons (11,2%). The jaw was
      the most affected place (35%), followed by zygoma (24%) and by the nose (23%),
      though most patients presented a single facial fracture (82,5%). Among the
      causes, accidents with automobiles (28,3%), aggression (21%) and accidental fall
      s (19,5%) were the most common. CONCLUSIONS: Accidents with automobiles continue
      being the main cause of facial trauma, especially of multiple fractures due to
      the great transmission of kinetic energy.

PMID- 16951859
TI  - Efficacy of functional endoscopic sinus surgery for symptoms in chronic
      rhinosinusitis with or without polyposis.
AB  - Functional endoscopic sinus surgery is the preferred treatment for chronic
      rhinosinusitis currently. Success on symptoms relief and quality of life
      improvement are the study leading objectives. STUDY DESIGN: retrospective
      clinical trial. METHODS: Questionnaires were given to the patients referred to
      Hospital das Clinicas-UFPE to chronic rhinosinusitis (CRS) functional endoscopic
      sinus intervention during 2003-2004. Symptoms outcome before and after surgery
      were compared and analyzed using a five-point-ranking scale. RESULTS: Twenty-four
      patients answered the questions. Eleven patients had CRS and 13 had CRS
      associated with nasal polypos. Quality of life was restricted by CRS in everyone,
      with a good improvement in 54,2% cases. All patients could recommend functional
      endoscopic sinus surgery to someone with same nasal problems and only 3 would not
      get surgery again. The best symptoms relief results were: nasal obstruction
      (83,3%), cacosmia/halitosis (80%), hyposmia/anosmia (63,15%), headache (62%).
      Patients with polyps achieved better symptomatic response than patients with only
      CRS. CONCLUSIONS: The leading symptoms were improved by functional endoscopic
      sinus surgery but not so much we expect. Allergic rhinitis presenting, not using
      nasal spray, poor ambient control influenced this result. Polyps patient achieved
      better symptoms outcome and quality of life responses on the most of symptoms
      than CRS patients.

PMID- 16951860
TI  - Microbiology of peritonsillar abscesses.
AB  - AIM: The objective of the present study was to analyze the microbiology of
      peritonsillar abscesses. METHODS: Thirty patients, mean age 24,2 years, with
      peritonsillar abscesses underwent aspiration of at least 3 mL of pus, which was
      cultured for aerobes and anaerobes. RESULTS: 87% samples showed positive
      cultures. Aerobic or facultative aerobic bacteria were isolated from 23%
      aspirates, mixed aerobic and anaerobic bacteria from 60%, and anaerobic bacteria
      from only 3% aspirate. A total of 69 bacterial isolates (34 aerobic and 35
      anaerobic) were recovered. The most common aerobic isolate was Streptococcus sp,
      with Streptococcus pyogenes being identified in 23% of aspirates. The predominant
      anaerobic isolates were Prevotella sp and Peptostreptococcus sp. Patients had
      received previous antimicrobial therapy in 63% cases. In this group, 1.8 isolates
      per specimen were recovered, a lower number than in the untreated group (3.0 per
      specimen). No significant difference in the species isolated was observed between
      these two groups. CONCLUSION: Peritonsillar abscess is usually a polymicrobial
      infection, with predominance of anaerobic bacteria. The number of agents isolated
      was larger in patients not previously treated with antibiotics, but the use of
      antimicrobial drugs did not interfere with the type of bacterium isolated.

PMID- 16951861
TI  - Evaluation of the utility of histopathologic exam as a routine in
      tonsillectomies.
AB  - Tonsillectomy is one of the most commonly performed procedures of the head and
      neck. It is performed for a wide variety of indications in both adults and
      children. It is common to send the material achieved in the surgery to routine
      histopathologic exam, as to analyze suspected material or for a medical-legal
      documentation. OBJECTIVE: Analyze the utility and cost of routine histopathologic
      diagnosis for tonsillectomy. METHODOLOGY: retrospective study of the
      histopathologic result of all tonsillectomies between 1978 and 2004 in a
      university hospital and analyzed the files of the patients with cancer. RESULTS:
      2103 results of histopathologic exams were analyzed. Of these, only four cases
      presented any case of malignancy, being all of these non-Hodgkin lymphoma and
      already suspected before the surgery. DISCUSSION: The world literature has
      encountered similar results and each time more the histopathologic analysis of
      all cases is questioned. The cost of the exam is high and your results, in the
      case of malignancy were already knew before the surgery. CONCLUSION:
      Histopathologic analysis of all tonsillectomies is not indicated. The risks
      factors established by Beaty should guide the solicitation of the exam, to try to
      low the costs with unnecessary exams.

PMID- 16951862
TI  - Effects of physical exercise in nasal volume.
AB  - The nasal permeability has been demonstrated using several exams. Nasal
      structures produces a resistance to the nasal air flux that represents over 50%
      of the total respiratory resistance. Physical exercises is a factor that brings a
      vasoconstrictor effect over nasal mucosa. AIMS: Evaluate the improvement degree
      of nasal volume after aerobic physical exercises and time to return to previous
      levels. SUBJECTS AND METHODS: Nineteen healthy subjects were submitted to aerobic
      exercise in ergometric bike. The nasal volume was obtained by Acoustic Rhinometry
      performed in rest, after aerobic exercise, 10o and 20o minutes after the aerobic
      exercise. RESULTS: Rhynometrics results shows a statically and significant
      increase of nasal volume (p<0,001). The nasal volume, in twenty minutes, returns
      nearby the rest levels. CONCLUSIONS: Aerobic exercises, generally, increases the
      nasal volume. However, the increase of nasal volume was transitory, and occurs a
      major reduction of increase in the first ten minutes after the exercises ends,
      and perform a greater vasoconstrictor effect over nasal mucosa, Twenty minutes
      after the physical exercises finish, total nasal volume returns, closely, to the
      basal levels.

PMID- 16951863
TI  - Impact in vocal quality in partial myectomy and neurectomy endoscopic of
      thyroarytenoid muscle in patients with adductor spasmodic dysphonia.
AB  - Impact in vocal quality in partial myectomy and neurectomy endoscopic of
      thyroarytenoid muscle in patients with adductor spasmodic dysphonia the adductor
      spasmodic dysphonia is a severe vocal disorder characterized by muscle laryngeal
      spasms during speech, producing phonatory breaks, forced, strained and strangled
      voice. Its symptoms come from involuntary and intermittent contractions of
      thyroarytenoid muscle during speech, which causes vocal fold strain, pressed one
      against another and increased glottic resistance. AIM: report the results in the
      impact in vocal quality in neurectomy of the thyroarytenoid branch of the
      inferior laryngeal nerve by endoscopic route associated with partial myectomy of
      the thyroarytenoid muscle with co2 laser. MATERIAL AND METHODS: the surgery was
      done in 07 patients (06 females and 01 male), aged 22 to 75, with adductor
      spasmodic dysphonia. They were submitted to vhi (voice handicap index) before and
      after surgery. RESULTS AND CONCLUSIONS: the vocal improvement was obtained in all
      studied patients, deterioration in vocal quality after surgery was not noticed.
      There was evident difference in the vhi before and after surgery. This surgical
      technique proved to be efficient and innovative in the treatment of adductor
      spasmodic dysphonia.

PMID- 16951864
TI  - Tympanoplasty: surgical results and a comparison of the factors that may
      interfere in their success.
AB  - Chronic otitis media has a high prevalence on the population and their treatment
      continuous to be a challenge for the otorhinolaryngologists. AIM: To demonstrate
      the factors that could interfere in the tympanoplasty success and the surgical
      results during 2002. STUDY DESIGN: Clinical prospective. MATERIAL AND METHOD:
      were included 37 patients with chronic otitis media non cholesteatoma (COMNC)
      undergo to tympanoplasty (in lay or underlay, with homologous graft). All the
      patients were submitted to a survey pre and postoperative include clinical,
      physical examinations, flexible nasal endoscope and audiometry. RESULTS: The age,
      the dimension and localization of the tympanic membrane perforation; the
      condition of middle ear mucosa; number of otorrhea/year; smoking; parents history
      of otorrhea and hearing loss; personals history of otological surgery; monthly
      family income; the graft, technique and access used were not significantly to
      repair tympanic membrane perforations. The closure rate was 65% and the gain in
      air-bone gap was 100%. CONCLUSION: The timpanoplasty must be considerate in the
      treatment of the COMNC.

PMID- 16951865
TI  - Prevalence of human papillomavirus (HPV) in oral cavity and oropharynx.
AB  - The prevalence of human papillomavirus (HPV) in the oral cavity and oropharynx
      has not yet been as well studied as its infection of the vaginal tract. However,
      new study are emerge after the development of molecular biology techniques. The
      objective of this study is to show the prevalence of HPV in the oral cavity and
      the oropharynx. An ample bibliographic review was done showing a prevalence of
      HPV 6, 11 in a normal oral mucous membrane (latent infection). In oral benign
      lesions associated with HPV, a prevalence of HPV 6 and 11 was observed in
      squamous cell papilloma (SCP) and condylomas acuminatum, while HPV 2 and 57 were
      more prevalent in verruca vulgaris lesions. As for focal epithelial hyperplasia
      (FEH) and oral cancer, especially squamous cell carcinoma (SCC), the prevalence
      was of HPV 13 and 32, and HPV 16, respectively. The last findings are,
      nonetheless, controversial. The last findings are, nonetheless, controversial.
      Showed also discrepancy result the prevalence of human papillomavirus (HPV) in
      normal oral mucous (latent infection) and in oral cancer, however evidenced
      confirmatory result in oral benign lesions associated with virus.

PMID- 16951866
TI  - Orbital endoscopic decompression in Graves ophthalmopathy.
AB  - Graves disease may lead to exophthalmos that is cosmetically unacceptable or
      causes visual loss. This has been managed surgically by external orbital
      decompression. However, a new minimally invasive endoscopic orbital decompression
      technique is now possible, with resection of the medial and posterior portion of
      the orbital limits requiring no cutaneous or gingival incisions. This technique
      produces decompression comparable to that obtained by external techniques.
      Endoscopic orbital decompression is a safe and effective procedure for the
      treatment of thyroid orbitopathy.

PMID- 16951867
TI  - Chagas disease: successes and challenges.

PMID- 16951868
TI  - Complementary and alternative medicine in Brazil: one concept, different
      meanings.
AB  - This article discusses the various meanings ascribed to the concept of
      Complementary and Alternative Medicine (CAM) in Brazil, where research on this
      theme has a limited tradition in terms of influences from anthropology, sociology
      of knowledge and epistemology, and sociology of CAM and clinical medicine. By
      means of the concepts identified in the literature, we elaborated a table with
      types of meanings. The terms Alternative Medicine and Complementary Medicine were
      found in more than one of the types in the table. Alternative Medicine identifies
      a model of medical practice influenced by the social, political, and economic
      context and by the logic of scientific production based on opposing pairs.
      Beginning in the 1980s, the important volume of reflections on official medical
      practice and the search for other forms of knowledge production led to the
      creation of the concept of Complementary Medicine. Its meaning is that of a new
      epistemological form of knowledge production between the official and alternative
      poles, a set of therapeutic practices, and confusion with the nomenclature for
      ancillary medical diagnostic tests, referred to in Portuguese as "complementary
      exams".

PMID- 16951876
TI  - Periodontal infection and adverse pregnancy outcomes: a systematic review of
      epidemiological studies.
AB  - The objective of this systematic review was to evaluate analytical studies on
      periodontal disease as a possible risk factor for adverse pregnancy outcomes. A
      literature search of the MEDLINE, SciELO, and LILACS bibliographic databases and
      CAPES thesis database was conducted up to December 2005, covering epidemiological
      studies of periodontal disease and adverse pregnancy outcomes. Of the 964 papers
      identified, 36 analytical studies met the inclusion criteria. Twenty-six
      epidemiological studies reported associations between periodontal disease and
      adverse pregnancy outcomes. There was a clear heterogeneity between studies
      concerning measurement of periodontal disease and selection of type of adverse
      pregnancy outcome. Therefore no meta-analysis was performed. Most studies did not
      control for confounders, thus raising serious doubts about their conclusions. The
      methodological limitations of most studies did not allow conclusions concerning
      the effects of periodontal disease on adverse pregnancy outcomes. Larger and
      methodologically rigorous analytical studies using reliable outcomes and exposure
      measures are recommended.

PMID- 16951877
TI  - [Palliative care in cancer: elements for debating the guidelines].
AB  - The aim of this study was to present elements for debating guidelines on
      palliative care programs for cancer. A literature survey searched various
      databases (MEDLINE, LILACS, and Cochrane Library), homepages of palliative care
      organizations, publications by renowned authors in this area, reference textbooks
      on the subject, relevant articles cited by these books, and the
      thesis/dissertation database of CAPES (the Brazilian Coordinating Body for
      Training University Level Personnel). The data were grouped into four thematic
      categories: symptomatic palliation, organization of services, psychosocial
      characteristics, and spiritual characteristics. The article then proceeds to
      discuss cancer as a public health problem and its impact on individuals, the
      concept of palliative care and its context in health care, program models and
      their guidelines, death and dying, and care and caregivers. The study concludes
      by discussing the challenges for the Brazilian National Health System in
      structuring end-of-life programs as a consequence of the population's aging and
      increasing cancer incidence.

PMID- 16951878
TI  - Factors associated with cesarean sections in a public hospital in Rio de Janeiro,
      Brazil.
AB  - Brazil has one of the world's highest cesarean section rates. Contributing
      factors include the organization of obstetric practice, physicians' attitudes,
      and women's preferences and decisions. This study aimed to identify factors
      associated with cesarean sections in a public maternity hospital in Rio de
      Janeiro. A case-control study was conducted with 231 cesarean sections (cases)
      and 230 vaginal deliveries (controls). Hierarchical logistic regression analysis
      was performed, based on a conceptual model. Factors associated with increased
      odds of cesarean section were: primiparity; mother's age 20-34; last birth by
      cesarean; cervical dilatation < 3cm at admission; patient request; daytime birth;
      male attending obstetrician; obstetrician on duty for more than 24 hours a week;
      obstetrician with private practice; gestational hypertension; non-cephalic
      presentation; and gestational age > 41 weeks. Factors associated with lower odds
      of cesarean were: gestational age < 37 weeks; leaving home with signs of labor,
      use of oxytocin; and amniotomy. In this hospital, interventions aimed to modify
      the above-mentioned factors can help lower the cesarean rate.

PMID- 16951879
TI  - [Frequency and spatial distribution of Aedes aegypti and Aedes albopictus
      (Diptera, Culicidae) in Rio de Janeiro, Brazil].
AB  - We evaluated the intra- and peri-domiciliary distribution of Aedes aegypti and
      Ae. albopictus in urban, suburban, and rural districts in the municipalities of
      Nova Iguacu and Rio de Janeiro, Brazil, from August 2002 to July 2004. Mostly Ae.
      aegypti females and males were captured in urban areas (56%) and indoors (78%),
      suggesting a preference by this species to rest inside houses and in areas with
      high human density, a behavior that favors vector-human contact. Meanwhile, Ae.
      albopictus females and males were much more common in rural areas (93%) and
      outdoors (90%), demonstrating their preference to rest in areas with more
      vegetation, reducing both the probability of vector-human contact and thus their
      potential role in dengue transmission in the area.

PMID- 16951880
TI  - [Cross-cultural adaptation and reliability analyses of the Southampton Assessment
      of Mobility to assess mobility of Brazilian elderly with dementia].
AB  - The objective was to perform a cross-cultural adaptation of the Southampton
      Assessment of Mobility and test its intra- and inter-examiner reliability for
      Brazilian elderly living in the community and diagnosed with dementia, with
      severity classified according to the Clinical Dementia Rating. The instrument was
      applied to 107 elderly (76.26 years +/- 7.59; 27.1% males, 72.9% females)
      diagnosed with dementia by the geriatric clinic at the university hospital of the
      Federal University in Minas Gerais. From the initial group, a randomized sample
      of 39 elderly (76.85 years +/- 7.75; 23.1% males, 76.9% females) was selected for
      the reliability tests. The statistical tool was the kappa test. The respective
      reliability indices were: mild dementia - 0.89-0.86; moderate - 0.79-0.85; and
      severe - 0.53-0.49. After cross-cultural adaptation and reliability tests, the
      instrument proved adequate for the target population, with "near-perfect"
      reliability for mild and moderate dementia. For severe dementia, the reliability
      was moderate.

PMID- 16951881
TI  - [Influence of socio-cultural context on risk perception and negotiation of
      protection among poor homosexual males on the Peruvian coast].
AB  - This paper focuses on risk, conceived not as an individual action, but
      considering its social dimension, analyzing the various forms in the socio
      cultural context related to internalized homophobia and hegemonic gender norms
      that allow barriers to be constructed in risk perception. Such barriers hinder
      negotiation and protection among homosexual men that have adopted a female gender
      identity, living in low-income barrios of Lima and Trujillo, Peru. Risk
      perception is analyzed on the socio-cultural plane, allowing one to explain the
      limited negotiating capacity of this population, even though they have extensive
      knowledge of HIV/AIDS and its consequences.

PMID- 16951882
TI  - [Trends in oral cancer mortality in the city of Sao Paulo, Brazil, 1980-2002].
AB  - The current study assessed trends in oral cancer mortality in the city of Sao
      Paulo, Brazil, from 1980 to 2002. The official mortality information system
      supplied data on deaths whose underlying cause was classified as oral cancer,
      stratified by sex, age, and anatomic site. Death rates were estimated and
      adjusted by the direct method, using population data supplied by national
      censuses from 1980, 1991, and 2000 and a population count performed in 1996.
      There was an upward trend in overall cancer mortality, at a yearly rate of 0.72%.
      Accounting for more than one third of these deaths, tongue cancer was the main
      mortality category. Labial, gengival, and retromolar cancer showed a downward
      trend, while oropharyngeal cancer and cancer in unspecified parts of the mouth
      and oropharynx showed increasing mortality. Monitoring the magnitude and trends
      in cancer mortality can assist the planning of health initiatives aimed at
      reducing the disease burden from oral cancer in Brazil.

PMID- 16951883
TI  - [Relationship between health care professionals and HIV positive women: a gender
      approach].
AB  - This article presents the results of research in 2003 focusing on the
      relationship between health care professionals from a public clinic and HIV
      positive women, adopting a gender approach. Ten patients and seven attending
      professionals were interviewed on the following themes: gender representations;
      representations of HIV/AIDS in women; and accommodation and resistance strategies
      to internalized attitudes and values regarding the health professional/patient
      relationship. According to the results, health professionals attempted to adjust
      the treatment to the limited resources of both the institution and the patient,
      endeavoring to offer the most complete care possible. Their social imagery
      continues to portray the traditional role of woman/mother/wife, perceived as a
      victim. Meanwhile patients adopted a "fighting woman" image, reinforced by the
      "modern woman" ideology, produced in both public and private spheres, disguising
      the effects of the women's double workload. Contrary to the myth of passivity,
      patients took an active stance towards their treatment, negotiating with health
      professionals about their own needs and objective possibilities. Despite the
      material and symbolic limitations, the potential was identified for changes in
      health care in order to achieve full reproductive rights.

PMID- 16951884
TI  - [Occupational noise exposure and work accidents].
AB  - The purpose of this study was to verify whether occupational noise exposure is a
      significant risk factor for work accidents in the city of Piracicaba, Sao Paulo
      State, Brazil. This hospital-based case-control study included 600 workers aged
      15-60 who suffered typical occupational accidents between May and October 2004
      and were seen at the Piracicaba Orthopedics and Trauma Center. The control group
      comprised 822 workers, aged 15-60, who were also seen at the Center, and either
      had a non-occupational accident or were accompanying someone who had suffered an
      accident. A multiple logistic regression model was adjusted with work accident as
      an independent variable, controlled by covariables of interest such as noise
      exposure. The risk of having a work accident was about twice as high among
      workers exposed to noise, after controlling for several covariables. Occupational
      noise exposure not only affected auditory health status but was also a risk
      factor for work accidents.

PMID- 16951885
TI  - [Internal migration and distribution of Chagas disease mortality, Brazil, 1981
      1998].
AB  - In Brazil, mortality from Chagas disease occurs even in regions classified as
      free of vector transmission. Because death rates refer to residents, and
      considering that a huge migratory movement has occurred inside the country, this
      study was intended to quantify the contribution of Brazilian internal migration
      to overall mortality from Chagas disease, from 1981 to 1998. If the PAHO Southern
      Cone Initiative actually achieved its objectives, one could expect declining
      death rates and increasing age at death from this cause. The results showed that
      out of 68,936 deaths in Brazilians with known birthplace, 32,369 (32%) occurred
      in people born in States other than those of their current residence (range: from
      0.3% in Rio Grande do Sul to 100% in Roraima and Amapa). Most (67%) of the deaths
      in migrants occurred in individuals born in the States of Minas Gerais (51%) and
      Bahia (16%). Death rates in residents showed a consistent decline in the
      Southeast, South, and Central West of the country, but not in the Northeast and
      North, where median age at death was the lowest.

PMID- 16951886
TI  - [Risk discourse and prenatal genetic counseling].
AB  - Medicalization is a highly visible and widespread social phenomenon in Western
      societies which is expressed differently according to gender. Pregnancy is
      heavily medicalized, and a surveillance network surrounds pregnant women, holding
      them accountable for both their own health and the production of a healthy fetus.
      Prenatal risk control is proposed in a context where diagnostic and therapeutic
      possibilities overlap. This problem is aggravated by the fact that abortion is
      illegal in Brazil. The current article is the result of research in a genetic
      counseling unit that consisted of: observation of consultations, review of
      patient files, and interviews with health professionals. The highly medicalized
      context of genetic counseling is discussed, as well as physicians' perception of
      their own practice. The article also discusses the potential impact on women's
      decisions related to risks, techniques, exams, and their consequences.

PMID- 16951887
TI  - [Risk factors for cancer of the uterine cervix in Propria, Sergipe, Brazil].
AB  - Cervical cancer is highly incident in poor regions of developing countries. It is
      related to lifestyle factors that lead to human papillomavirus (HPV) infection.
      The aim of the study was to assess which factors are important in the development
      of HPV infection and consequent cervical cancer in the community of Propria,
      Sergipe, Brazil. To analyze the risk factors related to cervical cancer, a case
      control study was performed, matching cases and controls for age, place of
      residence, and socioeconomic status. Twenty cases of carcinoma of the uterine
      cervix and 80 controls were identified. Cases had more pregnancies and a higher
      proportion of women who had not done Pap smears. Women in the two groups lived
      with promiscuous partners, had deficient knowledge about cervical cancer and its
      risk factors, and were predominantly illiterate. We concluded that in the
      community of Propria, multiple pregnancies and failure to have Pap smears were
      associated with the occurrence of cervical cancer.

PMID- 16951888
TI  - [Brazilian validation of the Questionnaire of Smoking Urges].
AB  - This study was designed to validate the Brazilian version of the Questionnaire of
      Smoking Urges (QSU). The design was experimental, and participants were randomly
      distributed in groups of zero, 30, and 60 minutes of tobacco abstinence. The
      total sample was 201, with 67 males and 134 females, age ranging from 18 to 65 (M
      = 38.15). The instruments applied, besides QSU, were the Social and Demographic
      Data Form, Visual Analogue Scale to evaluate craving, Fagerstrom Test for
      Nicotine Dependence, and Beck Anxiety and Depression Inventories. Total variation
      in the two-factor factorial analysis was 57.76%, with a high inter-correlation (r
      = 0.726; p = 0.000). Factor 1 represented the anticipated relief of negative
      affect, nicotine abstinence symptoms, and urgent and overwhelming desire to
      smoke. Factor 2 represented the desire to smoke and the anticipation of smoking
      pleasure. Such results are contrary to those found in the original QSU. The
      Brazilian version proved to be an adequate and reliable instrument that can be
      used in both research and patient treatment.

PMID- 16951889
TI  - [Hemoglobin level and anemia in children in the State of Pernambuco, Brazil:
      association with socioeconomic and food consumption factors].
AB  - This study aimed to assess hemoglobin level and anemia prevalence and their
      association with food-consumption and socioeconomic variables. A cross-sectional
      survey was conducted in the State of Pernambuco, Brazil, in 1997, using three
      stage sampling which included 746 6-to-59-month-old children. Hemoglobin testing
      and a 24-hour food recall interview were performed. The anemia rate was 40.6% and
      was higher in the rural area and inversely proportional to age, income, and
      maternal schooling. Most children (88.9%) consumed cow's milk. Anemia was
      associated directly with the proportion of calories from cow's milk and
      indirectly with the iron level. Child's age, geographic area, per capita family
      income, maternal schooling, iron density (total, heme, and non-heme), and the
      proportion of calories from cow's milk in the diet were determinants for anemia.

PMID- 16951890
TI  - [Regional health systems management: a case study in Rio Grande do Sul, Brazil].
AB  - This article analyzes the management system in a health district in the State of
      Rio Grande do Sul, Brazil, through qualitative analysis, using a case study as
      the methodology and macro-organization theory as the analytical framework. For
      the current management system in the 6th Health Region, a clear mission statement
      and wide acceptance by health workers are facilitating factors for the current
      organizational practices within the health system. Nevertheless, the way health
      coordinators are currently prioritizing their time has diverted necessary
      resources from critical problems towards more remedial issues. The 6th Health
      Region has encouraged social control (or public oversight) in order to improve
      accountability. However, there is room for improvement in quality assurance
      management, since there were no well-defined goals, objectives, or
      accountability. Decentralized consultancy provided to the municipalities and the
      funding model itself have both promoted decentralization and autonomy, although
      the strategy requires better regional integration and greater commitment in
      managerial practices.

PMID- 16951891
TI  - [Public knowledge and attitudes concerning dengue in the Municipality of Sao
      Luis, Maranhao, Brasil, 2004].
AB  - A sample survey with 843 interviews in Sao Luis, Maranhao State, Brazil was
      conducted to assess community knowledge and concepts regarding dengue. The
      population's understanding and its socioeconomic, health, and environmental
      conditions were evaluated. Potential vector breeding sites were found in all the
      areas surveyed. Media (TV, radio, etc.) were the most important source of public
      information on the disease. However, a gap was observed between knowledge and
      attitudes towards vector prevention. Strategies are also needed to involve the
      population in more effective prevention of vector proliferation, thus helping
      control the disease in Sao Luis.

PMID- 16951892
TI  - [Suicide attempts recorded at a general hospital in Rio de Janeiro, Brazil].
AB  - Previous suicide attempts are an important predictor of both repeated attempts
      and suicide. This paper presents the profile of patients who had attempted
      suicide and were admitted to a general hospital in Rio de Janeiro, Brazil. From
      April 2001 to March 2002, 160 suicide attempts were recorded (68% women; 26%
      adolescents). Ingestion of pesticides and prescription drugs were the two most
      common methods used. The two methods had been used by similar numbers of women,
      while two-thirds of men had used pesticides. As for prevalence of factors
      associated with attempted suicide, 21% of patients had been in contact with
      health services within 30 days prior to the event, 28% mentioned previous suicide
      attempts, and 23% reported other cases of suicide or attempts in the family.
      Despite the limited data in Brazil, suicide attempts appear to be an important
      health problem, particularly among youth. Surveillance systems for suicide
      attempts could help expand knowledge on this problem.

PMID- 16951893
TI  - [Health consortia: a case study of best practices].
AB  - Local Health Consortia have been used as alternatives and innovative models for
      improving health care provision. They are closely linked to the strategy aimed at
      regionalizing health care in Brazil and are in keeping with the health sector's
      administrative reform process, seeking greater efficiency, rationality, and
      quality in the supply of services to the population. In the development of such
      forms of cooperation, we view some consortia as weak structures with a short
      lifespan, while others have survived for considerable lengths of time. This case
      study on the Penapolis Consortium, the oldest in Brazil (having lasted for 14
      years), examines the dynamics of cooperation and the reasons for its
      sustainability. Its formation is a mixture of restructuring the regional supply
      and the entrepreneurial spirit of its leaders, along with State incentives. The
      Consortium's local capacity to solve cases with quality care and flexible
      management has proven to be an important factor. Participants share the important
      notion that the operational rules are fair, and the reasons for its success stem
      from the collective perception of reasonably symmetrical political gains as the
      result of political cooperation.

PMID- 16951894
TI  - [Survival study of breast cancer patients treated at the hospital of the Federal
      University in Santa Maria, Rio Grande do Sul, Brazil].
AB  - This retrospective hospital-based study aimed to describe health conditions and
      to estimate the survival of 252 patients diagnosed with breast cancer and treated
      at the Mastology Outpatient Clinic at the University Hospital of the Federal
      University in Santa Maria, Rio Grande do Sul, Brazil, from 1980 to 2000. Analysis
      followed the Kaplan-Meier and Cox model. Mean age was 54, and 73.4% of the
      patients had a histological diagnosis of invasive ductal carcinoma, 63.9% showed
      no lymph node involvement, and 57.6% were clinical stage II. At the end of the
      study, 64.7% were alive and free of breast cancer and 5.1% had died of other
      causes. Five-year survival was 87.7% for all women, and prognostic factors
      associated with survival were tumor size (HR = 12.03; > 5cm), lymph node
      involvement (HR = 3.08; N1) and number (HR = 4.66; None), and estrogen (HR =
      0.34) and c-erbB-2 (HR = 2.51) receptors. Based on the results, intensive
      awareness-raising campaigns are vitally important for implementing breast cancer
      screening to achieve early diagnosis.

PMID- 16951895
TI  - [A study on organ transplantation waiting lines in Brazil's Unified National
      Health System].
AB  - This study analyzes the waiting lines for solid organ transplants in Brazil's
      Unified National Health System. By using a queuing theory model, we estimate the
      waiting times for different organs under alternative scenarios. The model reveals
      the elasticity of various waiting times with respect to arrival and service rates
      for organ transplantation within the system. Average waiting time for a solid
      organ transplant is very long and highly elastic in Brazil. The article discusses
      some important possibilities for reducing such waiting times.

PMID- 16951896
TI  - [Mortality from injuries among childbearing-age women in Cascavel, Parana,
      Brazil, 1991-2000].
AB  - Injuries comprise the main group of causes of mortality among women 15 to 35
      years of age in Brazil. The present study aimed to improve the knowledge
      concerning mortality by injuries, using a descriptive population-based approach,
      including all 869 death certificates for resident 10-49-year-old women from
      Cascavel, Parana State, who died between 1991 and 2000. Mortality from injuries
      was analyzed according to cause, age, and calendar year. Pearson chi-square was
      applied at p < 0.05. Injuries were the main group of causes of death up to 34
      years of age and for all women 15-45 (coefficient 29.4/100,000 women) and the
      third most common among women 35-45. Traffic accidents were the first external
      cause of death in all age groups. We conclude that female mortality in Cascavel
      can be greatly reduced by interventions addressed to control external causes of
      death among young women.

PMID- 16951897
TI  - [Accuracy of the probabilistic record linkage methodology to ascertain deaths in
      survival studies].
AB  - Probabilistic record linkage methodology has been increasingly used to ascertain
      outcomes in cohort studies. However, only a few studies have evaluated its
      accuracy. The aim of this study was to evaluate the accuracy of probabilistic
      record linkage methodology to ascertain deaths in a cohort of 250 elderly people
      hospitalized for fractures caused by falls. The vital status of cohort members
      was determined through household visits conducted at one and six months after
      hospital admission. Record linkage was used to link records from the cohort to
      the Rio de Janeiro State mortality database. Deaths identified by the latter
      process were compared to the results obtained by active follow-up (gold
      standard). The vital status of 20 cohort members could not be determined by
      active follow-up. Among the remaining 230, 60 died within 180 days after hospital
      admission. Record linkage had a sensitivity of 85.5%, specificity of 99.4%,
      positive predictive value of 98.1%, and negative predictive value of 94.9%. In
      conclusion, probabilistic record linkage appears to be a useful tool for
      identifying deaths in cohort studies conducted in Brazil.

PMID- 16951898
TI  - New perspectives on aspirin and the endogenous control of acute inflammatory
      resolution.
AB  - Aspirin is unique among the nonsteroidal anti-inflammatory drugs in that it has
      both anti-inflammatory as well as cardio-protective properties. The cardio
      protective properties arise form its judicious inhibition of platelet-derived
      thromboxane A2 over prostacyclin, while its anti-inflammatory effects of aspirin
      stem from its well-established inhibition of prostaglandin (PG) synthesis within
      inflamed tissues. Thus aspirin and the other NSAIDs have popularised the notion
      of inhibiting PG biosynthesis as a common anti-inflammatory strategy based on the
      erroneous premise that all eicosanoids are generally detrimental to inflammation.
      However, our fascination with aspirin has shown a more affable side to lipid
      mediators based on our increasing interest in the endogenous control of acute
      inflammation and in factors that mediate its resolution. Epi-lipoxins (epi-LXs),
      for instance, are produced from aspirin's acetylation of inducible cyclooxygenase
      2 (COX-2) and together with Resolvins represent an increasingly important family
      of immuno-regulatory and potentially cardio-protective lipid mediators. Aspirin
      is beginning to teach us what nature knew all along--that not all lipid mediators
      are bad. It seems that while some eicosanoids are pathogenic in a variety of
      diseases, others are unarguable protective. In this review we will re-count
      aspirin's colorful history, discuss its traditional mode of action and the
      controversies associated therewith, as well as highlight some of the new pathways
      in inflammation and the cardiovascular systems that aspirin has recently
      revealed.

PMID- 16951899
TI  - Gene therapy and chronic pain.
AB  - Chronic, unremitting pain is perhaps the most common reason that patients seek
      medical care. In general, conservative techniques, such as medical management,
      are implemented as first-line therapy. Local anesthesia and lytic procedures,
      followed by interventional techniques, such as dorsal column stimulation and
      intrathecal drug delivery systems, are second-line therapies. However, for
      refractory and severe pain, which is not adequately controlled by other modes of
      therapy, new emerging options, including molecular or gene therapy, may become
      more widely utilized as experimental results are translated into clinical
      options.

PMID- 16951900
TI  - Does passive leg activity influence oxygen saturation and activity in sedentary
      elderly adults?
AB  - This study aimed to investigate whether any physiological changes might have a
      clinically significant effect on function in sedentary, institutionalized, older
      adults treated by a passive training program. A total of 18 subjects (mean age
      60.7 +/- 3.4) with intellectual disability (ID) participated. We measured SpO2
      (arterial oxygen saturation) before, during, and after passive training, and used
      Barthel Index to measure daily living activities. The general trend indicated
      that inactive people with ID evidenced a continual increase in SpO2% levels and
      some functional gains during passive treatment, with superiority to manual
      passive treatment compared to mechanical active passive training. For current
      clinical practice, most sedentary patients who experience clinically significant
      deconditioning and desaturation can benefit from passive treatment.

PMID- 16951901
TI  - Inflammation of the gonad in prepubertal healthy children. Epidemiology,
      etiology, and management.
AB  - The prevalence, etiology, and proper management of acute gonadal inflammation in
      prepubertal children are still controversial, with some reports defining it as
      rare, while others have found it more prevalent. So far, there is no consensus on
      imaging studies or standard follow-up procedures. In the minority of the
      children, the inflammation is related to congenital genitourinary malformation
      and bacterial infection. The majority of children with gonadal inflammation are
      healthy and do not have any underlying malformations; in this group, the etiology
      is related to viral infection or torsion of the gonad appendix. Management is
      directed towards the etiology. Hence, when bacterial inflammation is suspected,
      antibiotics should be given and full evaluation of the urinary tract system
      should be performed. For patients with negative medical history, absence of
      fever, and normal urinalysis, the diagnosis of bacterial inflammation is very
      unlikely, and there is neither justification for antimicrobial antibiotic therapy
      nor for any further urinary tract imaging. Caution should be taken with nonverbal
      children and infants, or patients with any abnormal parameter. For these
      patients, we recommend initial management as for bacterial urinary tract
      infection, until urine cultures results are obtained. This paper provides a
      comprehensive review with the related medical literature.

PMID- 16951902
TI  - Evolutionary explanations of the "actuarial senescence in the wild" and of the
      "state of senility".
AB  - A large set of data suggests that progressive reduction of fitness and senile
      decay in vertebrates are in correlation with the decline of cell replication
      capacities. However, the limits in such capacities are hardly explained in
      evolutionarily terms by current gerontological theories that rule out fitness
      decline as something genetically determined and regulated, and therefore somehow
      favored by natural selection. Four theories are tested as possible explanations
      of the "increasing mortality with increasing chronological age in populations in
      the wild" ("IMICAW"[1]), alias "actuarial senescence in the wild"[2], and of the
      observed negative correlation between extrinsic mortality and the ratio between
      deaths due to intrinsic mortality and deaths due to extrinsic mortality. Only the
      theory attributing an adaptive value to IMICAW allows an evolutionary explanation
      for it and for the aforesaid inverse correlation, while the other three theories
      ("mutation accumulation", "antagonistic pleiotropy", and "disposable soma" th.)
      even predict a positive correlation. Afterwards, the same theories are tested as
      possible explanations for the "state of senility"[3], namely the deteriorated
      state of individuals in artificially protected conditions (captivity,
      civilization, etc.) at ages rarely or never observable in the wild. With the
      distinction between "damage resulting from intrinsic living processes"[4], alias
      "age changes"[5], and "age-associated diseases"[4,5], the same theory explaining
      IMICAW allows a rational interpretation of the first category of phenomena while
      another theory, the "mutation accumulation" hypothesis, gives an immediate
      interpretation for the second category. The current gerontological paradigm
      explaining the increasing mortality with increasing chronological age as
      consequence of insufficient selection should be restricted to the "age-associated
      diseases". For IMICAW, it should be substituted with the concept of a physiologic
      phenomenon genetically determined by a balance of opposite selective pressures-
      strictly in terms of kin selection--and, for "age changes", with the action of
      the same IMICAW-causing mechanisms at ages when selection becomes ineffective.

PMID- 16951903
TI  - Collagen fibril diameter in relation to bone site and to calcium/phosphorus
      ratio.
AB  - The collagen fibril diameter was measured in cortical bone samples from the
      femoral neck, rear and front tibia of female and male rats and rabbits using
      electron microscopy analysis. In most cases, statistically significant
      differences in mean fibril diameter values between different bone sites were
      detected. The order of magnitude for the above structural parameter was the same
      for both genders in both experimental species. In rats, the greatest mean
      diameter value was that for the femoral, while in rabbits, the one for the rear
      tibia demonstrating a dependence on bone use and life style. An important aspect
      was the agreement between these observations and the mean values for Ca/P ratio,
      as observed in previous experiments, in the same bone sites and animals. Collagen
      fibril diameter and Ca/P ratio can both serve as indexes of bone quality.

PMID- 16951904
TI  - Myelin structure and composition in zebrafish.
AB  - To establish a standard for genotype/phenotype studies on the myelin of zebrafish
      (Danio rerio), an organism increasingly popular as a model system for
      vertebrates, we have initiated a detailed characterization of the structure and
      biochemical composition of its myelinated central and peripheral nervous system
      (CNS; PNS) tissues. Myelin periods, determined by X-ray diffraction from whole,
      unfixed optic and lateral line nerves, were approximately 153 and approximately
      162 Angstrom, respectively. In contrast with the lability of PNS myelin in higher
      vertebrates, zebrafish lateral line nerve myelin exhibited structural stability
      when exposed to substantial changes in pH and ionic strength. Neither optic nor
      lateral line nerves showed swelling at the cytoplasmic apposition in CaCl(2)
      containing Ringer's solution, in contrast with nerves from other teleost and
      elasmobranch fishes. Zebrafish optic nerve showed greater stability against
      changes in NaCl and CaCl(2) than lateral line nerve. The nerves from zebrafish
      having mutations in the gene for myelin basic protein (mbpAla2Thr and
      mbpAsp25Val) showed similar myelin periods as the wildtype (WT), but gave
      approximately 20% less compact myelin. Analysis of proteins by SDS-PAGE and
      Western blotting identified in both CNS and PNS of WT zebrafish two orthologues
      of myelin P0 glycoprotein that have been characterized extensively in trout-
      intermediate protein 1 (24 kDa) and intermediate protein 2 (28 kDa). Treatment
      with endoglycosidase-F demonstrated a carbohydrate moiety of approximately 7 kDa,
      which is nearly threefold larger than for higher vertebrates. Thin-layer
      chromatography for lipids revealed a similar composition as for other teleosts.
      Taken together, these data will serve as a baseline for detecting changes in the
      structure and/or amount of myelin resulting from mutations in myelin-related
      genes or from exogenous, potentially cytotoxic compounds that could affect myelin
      formation or stability.

PMID- 16951905
TI  - Deep brain stimulation: overview and update.
AB  - OBJECTIVE: To summarize the techniques for physiological localization that
      contribute to increased accuracy in the surgical treatment of movement disorders.
      METHODS: Initial targeting through imaging referenced to stereotactic atlas are
      confirmed through physiological localization. Spontaneous recording, elicited
      recording, evoked potentials and stimulation provided physiological localization
      for target confirmation in the placement of lesions or DBS. RESULTS: Imaging and
      stereotactic techniques produce inaccuracy that may be address by physiological
      localization. Microelectrode recording from basal ganglia and thalamic sites
      provides signature neuronal patterns to confirm and guide the trajectory.
      Spontaneous and elicited neuronal response are recorded from microelectrodes.
      CONCLUSIONS: Accuracy of movement disorders surgery is enhance through use of
      physiological localization. A multimodality approach provides techniques that
      allow localization in a variety of patient and environmental conditions.

PMID- 16951906
TI  - Mechanism for proliferation inhibition by various selenium compounds and selenium
      enriched broccoli extract in rat glial cells.
AB  - The objective of this study was to investigate the differential effects of
      various selenium (Se) compounds and Se-enriched broccoli extracts on cell
      proliferation and the possible mechanism responsible for the Se-induced growth
      inhibition. C6 rat glial cells were incubated with graded concentrations up to
      1000 nM of selenite, selenate, selenomethionine (SeM), Se-methyl-selenocysteine
      (SeMCys), high-Se broccoli (H-SeB) extract or low-Se broccoli (L-SeB) extract for
      24 and 48 h. MTT results indicated that all Se sources and levels examined
      inhibited C6 cell proliferation at 48 h. The results from cell cycle progression
      and apoptosis analysis indicated that SeM, SeMCys, H-SeB or L-SeB treatments at
      the concentration of 1000 nM reduced the cell population in G(0)/G(1) phase, but
      induced G(2)/M phase arrest and increased apoptosis and secondary necrosis in C6
      cells at 24 h. The populations of apoptotic cells and secondary necrotic cells
      were increased by all Se sources examined. The COMET assay indicated that there
      was no significant DNA single-strand break found for all Se treatments in C6
      cells for 48 h. In addition, the Se-induced proliferation inhibition may involve
      a hydrogen peroxide (H(2)O(2))-dependent mechanism with elevated cellular
      glutathione peroxidase (cGPX) activity. Both H-SeB and L-SeB inhibited C6 cell
      proliferation but H-SeB was less inhibitory than L-SeB. The proliferation
      inhibition by H-SeB in C6 cells is apparently related to the increased H(2)O(2)
      with the elevated cGPX activity, but the inhibition by L-SeB was H(2)O(2)
      independent without change in cGPX activity.

PMID- 16951907
TI  - Use of clinical risk factors to identify postmenopausal women with vertebral
      fractures.
AB  - INTRODUCTION AND HYPOTHESIS: Previous studies have been unable to identify risk
      factors for prevalent vertebral fractures (VF), which are suitable for use in
      selection strategies intended to target high-risk sub-groups for diagnostic
      assessment. However, these studies generally consisted of large epidemiology
      surveys based on questionnaires and were only able to evaluate a limited number
      of risk factors. Here, we investigated whether a stronger relationship exists
      with prevalent VF when conventional risk factors are combined with additional
      information obtained from detailed one-to-one assessment. METHODS: Women aged 65
      75 registered at four geographically distinct GP practices were invited to
      participate (n=1,518), of whom 540 attended for assessment as follows: a
      questionnaire asking about risk factors for osteoporosis such as height loss
      compared to age 25 and history of non-vertebral fracture (NVF), the get-up-and-go
      test, Margolis back pain score, measurement of wall-tragus and rib-pelvis
      distances, and BMD as measured by the distal forearm BMD. A lateral thoraco
      lumbar spine X-ray was obtained, which was subsequently scored for the presence
      of significant vertebral deformities. RESULTS: Of the 509 subjects who underwent
      spinal radiographs, 37 (7.3%) were found to have one or more VF. Following
      logistic regression analysis, the four most predictive clinical risk factors for
      prevalent VF were: height loss (P=0.006), past NVF (P=0.004), history of back
      pain (P=0.075) and age (P=0.05). BMD was also significantly associated with
      prevalent VF (P=0.002), but its inclusion did not affect associations with other
      variables. Factors elicited from detailed one-to-one assessment were not related
      to the risk of one or more prevalent VFs. The area under ROC curves derived from
      these regressions, which suggested that models for prevalent VF had modest
      predictive accuracy, were as follows: 0.68 (BMD), 0.74 (four clinical risk
      factors above) and 0.78 (clinical risk factors + BMD). Analyses were repeated in
      relation to the subgroup of 13 patients with two or more VFs, which revealed that
      in this instance, the Margolis back pain score and rib-pelvis distance were
      associated with the presence of multiple VFs (P=0.022 and 0.026, respectively).
      Moreover, the predictive value as reflected by the ROC curve area was improved:
      0.80 (BMD), 0.88 (the four most predictive clinical risk factors consisting of
      the height loss, past NVF, Margolis back pain score and rib-pelvis distance) and
      0.91 (clinical risk factors + BMD). CONCLUSIONS: Evaluation of additional risk
      factors from detailed one-to-one assessment does not improve the predictive value
      of risk factors for one or more prevalent vertebral deformities in postmenopausal
      women. However, the use of factors such as the Margolis back pain score and rib
      pelvis distance may be helpful in identifying postmenopausal women at high risk
      of multiple prevalent VFs.

PMID- 16951908
TI  - Effects of parathyroid hormone alone or in combination with antiresorptive
      therapy on bone mineral density and fracture risk--a meta-analysis.
AB  - AIM: The effects of parathyroid hormone (PTH) alone or in combination with
      antiresorptive therapy on changes in bone mineral density (BMD) and fracture risk
      were studied. MATERIALS AND METHODS: Randomised placebo controlled trials were
      retrieved from the PubMed, Web of Science or Embase databases. RESULTS: PTH alone
      or in combination with antiresorptive drugs reduced vertebral [relative risk
      (RR)=0.36, 95% confidence interval (CI): 0.28-0.47, 2p<0.01] and non-vertebral
      (RR=0.62, 95% CI: 0.48-0.82, 2p<0.01) fracture risk and increased spine BMD by
      6.6% (95% CI: 5.2-8.1%, 2p<0.01) and hip BMD non-significantly by 1.0% (95% CI: 
      0.1 to 2.1%, 2p=0.08) during 11-36 months of follow-up (13 trials). The gain in
      spine and hip BMD tended to increase with the length of the PTH treatment. No
      significant effect of study duration on fracture risk could be demonstrated. The
      major adverse events were hypercalcaemia, nausea and discomfort at the injection
      sites. Only limited data are currently available on fracture risk reduction with
      PTH plus antiresorptive therapies. CONCLUSION: Although the number of studies on
      non-vertebral fractures is limited, our pooled analysis revealed that PTH alone
      or in combination with antiresorptive drugs would appear to be able to reduce the
      risk of vertebral and non-vertebral fractures and to increase spine and perhaps
      hip BMD. However, these analyses were based on cross-sectional data--i.e. based
      on indirect comparisons--and further studies with a direct comparison of study
      duration are necessary. No studies comparing PTH, PTH plus antiresorptive drugs
      and antiresorptive drug versus placebo in a factorial design are available;
      consequently, we were unable to draw any conclusions on the superiority of PTH
      plus antiresorptive drug versus antiresorptive drug or PTH alone with respect to
      BMD or fractures.

PMID- 16951909
TI  - Idiopathic juvenile osteoporosis--an analysis of the muscle-bone relationship.
AB  - INTRODUCTION: Idiopathic Juvenile Osteoporosis (IJO), a disease of unknown
      etiology, manifests typically by pain, bone deformities and fractures. Due to
      limits in BMD data interpretation, evaluation of the muscle-bone functional unit
      has recently been proposed as a means to assess the general competence of the
      skeleton. The aim of this study was to evaluate skeletal status during the acute
      phase of IJO and during recovery from the disease in relation to muscles.
      MATERIALS AND METHODS: The study population comprised 61 IJO children, including
      34 girls (mean age: 13.6+/-3.1 years; range: 7-18) and 27 boys (14.3+/-3.3; 5-18
      years). DXA total body (TB) and lumbar spine (S) bone mineral content (BMC) and
      density (BMD) were measured. Lean body mass (LBM) was employed to calculate
      SBMC/LBM, TBBMC/LBM, body height (BH)/LBM and LBM/body weight (BW) ratios.
      Previously established references for healthy controls were utilized for the
      calculation of Z-score values in IJO cases in respect to phase of the disease.
      RESULTS: IJO patients had significantly decreased Z-score values for TBBMD, SBMD,
      SBMC/LBM and TBBMC/LBM ratios but not for the LBM and BH/LBM or LBM/BW ratios.
      During the acute phase IJO girls had mean Z-scores for TBBMD and SBMD of -2.49+/
      0.61 and -3.27+/-1.03, respectively, which were significantly lower than Z-scores
      during the recovery phase: -0.90+/-0.66, -1.38+/-0.95 (p<0.0001). IJO boys during
      the acute phase had Z-scores of -2.08+/-0.65 and -2.75+/-1.19 for TBBMD and SBMD,
      respectively, which were significantly lower than those during the recovery phase
      (-0.51+/-1.04 and -1.39+/-1.49; p<0.0001). Further, during the acute phase,
      TBBMC/LBM Z-scores of -2.95+/-1.15 and -2.56+/-1.49 were noted in girls and boys,
      respectively; the corresponding SBMC/LBM Z-scores were -2.66+/-1.07 and -2.22+/
      1.62. During the recovery from IJO, TBBMC/LBM and SBMC/LBM Z-scores of -1.07+/
      0.99 and -0.91+/-1.16 and of -1.15+/-1.40 and -0.68+/-1.45 were noted in girls
      and boys, respectively, and all were significantly higher than those during the
      acute phase (p<0.0001). CONCLUSIONS: The results of this study indicate that IJO
      is a bone disorder characterized by an imbalanced muscle-bone relationship and
      fractures at onset and during the acute phase and by at least a partial recovery
      without bone pain and new fractures. Implementation of the BH/LBM, TBBMC/LBM and
      SBMC/LBM ratios to the armamentarium of pediatricians diagnosing bone disorders
      will provide mechanically meaningful data for diagnostic purposes and, hopefully,
      for proper therapeutic decisions.

PMID- 16951910
TI  - Genetic determination and correlation of body weight and body mass index (BMI)
      and cross-sectional geometric parameters of the femoral neck.
AB  - INTRODUCTION: This study aimed to examine the genetic determination of body
      weight, body mass index (BMI) and cross-sectional geometric parameters of the
      femoral neck including cross-sectional area (CSA), cortical thickness (CT),
      sectional modulus (Z), and buckling ratio (BR), and to test the genetic
      correlation between body weight/BMI and the femoral neck geometric parameters.
      METHODS: A total of 929 healthy subjects from 292 Chinese nuclear families was
      included. Femoral neck geometric parameters were estimated from bone mineral
      density (BMD) and bone area which were measured by dual energy X-ray
      absorptiometry (DXA). RESULTS: The heritability (h(2)) estimate values were
      0.643, 0.626, 0.626, 0.674, 0.405, and 0.615 for body weight, BMI, CSA, CT, Z,
      and BR, respectively. Body weight was significantly correlated with bone
      geometric parameters (p</=0.001) with genetic correlation (rho(G)) values of
      0.551, 0.457, 0.571, and -0.385, and bivariate heritability (rho2G) values of
      0.304, 0.209, 0.326, and 0.148 for CSA, CT, Z, and BR, respectively. Similar
      correlations (p</=0.001) were observed between BMI and bone geometric parameters,
      with rho(G) values of 0.446, 0.432, 0.334, and -0.362, and (rho2G) values of
      0.199, 0.187, 0.112, and 0.131 for CSA, CT, Z, and BR, respectively. CONCLUSION:
      In summary, our study suggested that body weight, BMI, and femoral neck geometry
      were under strong genetic determination. The strong genetic correlations
      suggested that the genetic factors of bone geometry may be overlapped with those
      of body weight and BMI.

PMID- 16951911
TI  - Osteoporosis in men: are we referring enough for DXA and how?
AB  - The aim of the study is to determine the pattern of male referrals to an
      osteodensitometry unit in a tertiary hospital in UAE. In this study, we reviewed
      the records of male patients referred for dual X-ray absorptiometry over 9 months
      since the establishment of the unit. Indications for scanning were categorized
      into high and medium risk and infrequent causes of osteopenia/osteoporosis. They
      were ranked according to frequency. The outcome was documented by category and
      patients were considered normal when they have bone mineral densities (BMD) over
      0.82 g/cm(2), osteopenia between 0.60 and 0.82 g/cm(2), and osteoporosis below
      0.60 g/cm(2) for hips and lumbar spine. The site with the lowest value was taken
      as representative of the patient's BMD status. The ages of the patients ranged
      from 16 to 91 years (mean of 55.2 years). Male referrals made up 8.8% (71/805)
      over the 9-month period. The number of indications was 83 accounting for 1.16 per
      patient. Most common reasons were patients on corticosteroid therapy (20.5%),
      bone rarefaction on radiographs (13%), and fragility fractures (12%). Others
      included back pain, general aches and pains, querying osteoporosis, and
      miscellaneous causes that made up 8.5% each. These were followed by
      immobilization, (6%) arthropathies (6%), excess alcohol intake (3.5%), aging,
      (2.5%), and hepatorenal disorders (2.5%). A positive family history of
      osteoporosis, treatment for neoplasia, smoking, and chronic obstructive airway
      disease (1% each) were the least common reasons for referral. Thirty-five
      patients (49%) had osteopenia, 16 (22.5%) had osteoporosis, and 20 (28%) were
      normal. The low referral rate and relatively high normal outcome among men
      suggest that osteoporosis is still viewed as a disease of females. This aberrant
      referral pattern, when viewing the majority of indications, reflects an inability
      to prioritize the reasons for referral. It is prudent, therefore, to instill an
      awareness of the increasing importance of osteoporosis in men in the minds of the
      referring clinicians.

PMID- 16951912
TI  - Multimodal visualization interface for data management, self-learning and data
      presentation.
AB  - A multimodal visualization software, called the Data Manager (DM), has been
      developed to increase interdisciplinary communication around the topic of
      visualization and modeling of various aspects of the human anatomy. Numerous
      tools used in Radiology are integrated in the interface that runs on standard
      personal computers. The available tools, combined to hierarchical data management
      and custom layouts, allow analyzing of medical imaging data using advanced
      features outside radiological premises (for example, for patient review,
      conference presentation or tutorial preparation). The system is free, and based
      on an open-source software development architecture, and therefore updates of the
      system for custom applications are possible.

PMID- 16951913
TI  - Simple but aesthetically pleasant ending for a running subcuticular suture.

PMID- 16951914
TI  - Prevention of thromboembolism by saline solution perfusion.

PMID- 16951915
TI  - "Reverse" dual-plane mammaplasty.
AB  - BACKGROUND: The authors present a new type of dual-plane mammaplasty and
      preliminary results obtained with it. The technique is aimed at improving the
      final natural appearance of breasts without adding additional risks of
      dislocation. METHODS: The eligibility criteria specified patients with sufficient
      breast tissue to disguise the implant, patients with asymmetric hypoplasia, and
      patients with an intense workout activity. The exclusion criteria specified
      patients with very little breasts. The technique is based on combined
      subglandular positioning in the superior part of the breast and retrofascial
      precostal positioning in the inferior part. RESULTS: Beginning in January 2000,
      57 patients were recruited. No postoperative bleedings, hematomas, or seromas
      were observed. In 93% of cases, good final shapes were obtained. After 1 year of
      follow-up evaluation, no displacement, asymmetry, or rupture was recorded. Only
      three patients (5.3%) showed mild monolateral capsular contractures (Baker II
      type), which resolved using capsulotomy without prostheses removal. CONCLUSIONS:
      "Reverse" dual-plane mammaplasty is a new technique that gives a good anatomic
      final appearance with no risk of displacement. The low risk of complications
      renders it feasible and safe for aesthetic breast augmentation. Further studies
      are necessary to compare this technique with retroglandular and retropectoral
      approaches.

PMID- 16951916
TI  - Three-dimensional mandible reduction: correction of occlusal class I in skeletal
      class III cases.
AB  - BACKGROUND: The human face is a three-dimensional structure. However, many
      studies on mandible reduction procedures are based on a two-dimensional concept,
      with a particular focus on one dimension: the width of the lower face. Many
      Korean individuals have class I occlusion with a skeletal class III pattern. When
      a conventional mandible reduction procedure is used on such individuals to reduce
      the width of the lower face, an unsatisfactory facial outcome may result because
      the changes in the other two dimensions of the lower face, vertical height and
      anteroposterior distance, are disregarded. This is true because the skeleton of
      the lower face is well developed in all three dimensions. METHODS: Bimaxillary
      surgery that reduces all three dimensions of the lower face was planned and
      conducted by the authors. This mandible reduction procedure reduced the
      protrusion of both the maxilla and the mandible and, at the same time, shortened
      the lower face height. The procedure consisted of a Le Fort I osteotomy for
      superior and/or posterior repositioning of the maxilla, followed by mandibular
      counterclockwise rotation and setback via a bilateral sagittal split osteotomy.
      Genioplasty was performed as necessary. RESULTS: With this procedure, the entire
      lower face volume is reduced, and the overall profile is improved. CONCLUSIONS:
      Three-dimensional mandible reduction greatly enhances the aesthetic outcome by
      improving the skeletal characteristics of the face common in the Korean
      population so that the facial measurements more closely approach normal values.

PMID- 16951917
TI  - Four novel and three recurrent mutations of the BTK gene and pathogenic effects
      of putative splice mutations.
AB  - X-linked agammaglobulinemia is caused by mutations in the human BTK gene, leading
      to recurrent pyogenic infections. We describe four novel and three known BTK
      mutations in seven patients from seven (six Thai and one Burmese) families. All
      but one were sporadic cases. Patients 1 and 2 had recurrent mutations in exon 10
      (R288W) and exon 17 (R562W), respectively. Patient 3, a previously healthy
      individual who presented with pseudomonas sepsis with ecthyma gangrenosum had a
      known mutation in exon 17 (1749delT), leading to frameshift effect (F583fsX586).
      Patient 4 manifested with sepsis and concurrent acute appendicitis and pneumonia.
      He had a mutation, IVS8 + 1G > A, which led to an insertion of intron 8 into the
      transcripts. In Patient 5, a novel change in exon 7, c.588G > C, initially
      presumed Q196H, was found to cause a leaky splicing mutation, resulting in three
      distinct transcripts containing 17, 108, and 190 bp of the 5'-terminal of intron
      7, which led to truncated peptides consisting of 203 and 211 amino acid residues
      (or Q196fsX204 and Q196fsX212, respectively). Patient 6 had a mutation in exon 14
      (W421X), while patient 7 had a newly defined large deletion of exons 6-9. All of
      the mothers tested were mutation carriers. Transcript analysis in three mothers
      who were heterozygous for frameshift mutations revealed a minimal amount of
      aberrant transcripts, while their affected children had full expression of the
      mutant alleles, suggesting rapid degradation due to nonsense-mediated mRNA decay
      in the mothers. This is the first report of mutations of BTK from Thailand.

PMID- 16951918
TI  - Farber lipogranulomatosis: clinical and molecular genetic analysis reveals a
      novel mutation in an Indian family.
AB  - Farber disease is a rare lysosomal storage disorder caused by a deficiency of the
      acid ceramidase enzyme, leading to the accumulation of ceramide in various
      tissues. It usually manifests within a few months after birth with a unique triad
      of symptoms, including painful and progressive deformed joints, progressive
      hoarseness and subcutaneous nodules. The disease is inherited as an autosomal
      recessive trait, and mutations in the N-acylsphingosine amidohydrolase (ASAH1)
      gene, which codes for the acid ceramidase enzyme, have been shown to cause the
      disease. In the current study, we report the identification of a novel disease
      causing mutation in the ASAH1 gene that results in Farber disease in an Indian
      family. The mutation was identified in the eighth exon and is a missense mutation
      resulting in replacement of Valine by Leucine at codon 182. Two affected siblings
      harboured the identical mutation. The possible mechanism(s) of disease caused by
      this mutation are discussed.

PMID- 16951919
TI  - Is parenthood associated with mental health? Findings from an epidemiological
      community survey.
AB  - BACKGROUND: Despite some reports on a potential link between parenthood and
      mental health, associations have not been systematically investigated yet. The
      present article provides prevalence rates of the most common mental disorders for
      parents and non-parents. Interactions between demographic and socio-economic
      variables, parental status and mental health are explored. METHODS: Data from the
      1998/99 German Health Survey (GHS) and its Mental Health Supplement (GHS-MHS)
      were analysed using logistic regression models. Analyses were restricted to
      participants in the age group 18 to 49 (N=2,801). Mental disorders and syndromes
      were assessed with a standardized diagnostic interview (M-CIDI). RESULTS:
      Parenthood was associated with lower rates of psychiatric morbidity in general,
      and depressive and substance use disorders, in particular. The association
      between parental status and mental health was more distinct in men than in women,
      whereas partnership status moderated this relationship: An absence of partnership
      was associated with increased rates of all common mental disorders. Among non
      parents, such a difference could not be found. Full-time employment, compared to
      part-time employment or unemployment, was linked to lower rates of the common
      mental disorders among fathers but not among mothers and non-parents. Age,
      education and income had no effects on the association between parental status
      and mental health. CONCLUSION: Parenthood is positively associated with mental
      health, particularly for men. Most differences can be found for depressive and
      substance use disorders. Partnership seems especially important for parents since
      it does not affect prevalence rates of mental disorders among non-parents.

PMID- 16951920
TI  - Divergent trends in suicide by socio-economic status in Australia.
AB  - OBJECTIVES: This study investigated secular trends in socio-economic status (SES)
      differentials in Australian suicide (1979-2003), which includes overall declines
      in male suicide from 1998. METHOD: Suicide rates were stratified by approximate
      equal-population quintiles of area-based SES for the period 1979-2003 and
      examined across five quinquennia, centred on each Australian Census from 1981 to
      2001, to determine if (1) SES differentials in suicide have persisted over time,
      and (2) if SES differentials have widened or narrowed. Suicide rates (per
      100,000) were adjusted for confounding by sex, age, country-of-birth, and urban
      rural residence using Poisson regression models, and secular changes in SES
      differentials were assessed using trend tests on suicide rate ratios (low to high
      SES quintiles). RESULTS: Socio-economic status (SES) differentials persisted
      across the study period for both males and females after adjusting for the
      effects of age, migrant status, and urban-rural residence, with the largest
      differences between low and high SES groups evident in males, and especially
      young males (20-34 years). For males, suicide rates increased significantly in
      all SES groups until 1998, before diverging significantly in the most recent 5
      year period, particularly in younger males (P<0.0001). In young males, suicide
      rates in the most recent period increased in the low SES group from 44.8 in 1994
      1998 to 48.6 in 1999-2003 (an 8% increase). In contrast, suicide rates in the
      middle SES group decreased from a peak of 37.3 to 33.5 (a 10% decrease), and in
      the high SES group from a peak of 33.0 to 27.9 (a 15% decrease). A similar
      statistically significant divergence of a lesser magnitude was also evident in
      all age males and younger females (20-34 years). CONCLUSION: This study shows
      that SES differentials in suicide persisted in Australia for most of the period
      1979-2004. The decline in suicide in young males in the most recent quinquennium
      was limited to middle and high SES groups, while the low SES group displayed a
      continued increase. The continued increase in suicide in low SES males has
      implications for social and economic intervention and suicide control programs.

PMID- 16951921
TI  - Depressive symptoms and the risk of long-term sickness absence: a prospective
      study among 4747 employees in Denmark.
AB  - BACKGROUND: The aim of this paper is to examine the impact of depressive symptoms
      on long-term sickness absence in a representative sample of the Danish workforce.
      METHODS: This prospective study is based on 4,747 male and female employees,
      participating in the Danish Work Environment Cohort Study. Depressive symptoms
      were measured at baseline. Data on sickness absence were obtained from a national
      register on social transfer payments. Onset of long-term sickness absence was
      followed up for 78 weeks. RESULTS: The cumulative 78 weeks incidence for the
      onset of long-term sickness absence was 6.5% in men and 8.9% in women. Both men
      and women with severe depressive symptoms (<or=52 points) were at increased risk
      of long-term sickness absence during follow-up (men: HR=2.69; 95% CI: 1.18, 6.12;
      women: HR=2.27; 95% CI: 1.25, 4.11), after adjustment for demographic, health
      related, and lifestyle factors. When we divided the depressive symptom scores
      into quartiles, we found no significant effects with regard to long-term sickness
      absence. CONCLUSIONS: Severe depressive symptoms, as measured with the MHI-5,
      increased the risk of future long-term sickness absence in the general Danish
      working population. However, effects were not linear, but occurred mostly only in
      those employees with high levels of depressive symptoms.

PMID- 16951922
TI  - The effect of intracellular ascorbate on the susceptibility of HL60 and Jurkat
      cells to chemotherapy agents.
AB  - Chemotherapy agents initiate tumour cell apoptosis and this is thought to involve
      oxidative stress. In this study we have investigated the effect of the important
      antioxidant Vitamin C (ascorbate) on the response of HL60 and Jurkat cells to
      three chemotherapy drugs, namely etoposide, melphalan and arsenic trioxide
      (As(2)O(3)). Cells grown in routine culture media are deficient in ascorbate and
      to determine its effect on chemotherapy drug-induced apoptosis we supplemented
      the cells prior to drug exposure. We found that ascorbate had a varied effect on
      apoptosis and cell cycle progression. Etoposide-induced apoptosis in HL60 cells
      was significantly increased in ascorbate-loaded cells as measured by caspase-3
      activation and DNA degradation, and this appeared to reflect a decrease in the
      number of necrotic cells rather than increased cytotoxicity. In contrast,
      ascorbate had no effect on etoposide-induced apoptosis in Jurkat cells. In both
      cell types melphalan-induced apoptosis was unaffected by intracellular ascorbate,
      whereas both apoptosis and growth arrest with low concentrations of As(2)O(3)
      were diminished. These results indicate that intracellular ascorbate can affect
      cell responses to chemotherapy drugs in a complex and somewhat unpredictable
      manner and that it may play an important role in the responsiveness of tumour
      cells to chemotherapy regimes.

PMID- 16951923
TI  - Clearance of apoptotic and necrotic cells and its immunological consequences.
AB  - The ultimate and most favorable fate of almost all dying cells is engulfment by
      neighboring or specialized cells. Efficient clearance of cells undergoing
      apoptotic death is crucial for normal tissue homeostasis and for the modulation
      of immune responses. Engulfment of apoptotic cells is finely regulated by a
      highly redundant system of receptors and bridging molecules on phagocytic cells
      that detect molecules specific for dying cells. Recognition of necrotic cells by
      phagocytes is less well understood than recognition of apoptotic cells, but an
      increasing number of recent studies, which are discussed here, are highlighting
      its importance. New observations indicate that the interaction of macrophages
      with dying cells initiates internalization of the apoptotic or necrotic targets,
      and that internalization can be preceded by "zipper"-like and macropinocytotic
      mechanisms, respectively. We emphasize that clearance of dying cells is an
      important fundamental process serving multiple functions in the regulation of
      normal tissue turnover and homeostasis, and is not just simple anti- or pro
      inflammatory responses. Here we review recent findings on genetic pathways
      participating in apoptotic cell clearance, mechanisms of internalization, and
      molecules involved in engulfment of apoptotic versus necrotic cells, as well as
      their immunological consequences and relationships to disease pathogenesis.

PMID- 16951924
TI  - Bcl-2 protein family: implications in vascular apoptosis and atherosclerosis.
AB  - Apoptosis has been recognized as a central component in the pathogenesis of
      atherosclerosis, in addition to the other human pathologies such as cancer and
      diabetes. The pathophysiology of atherosclerosis is complex, involving both
      apoptosis and proliferation at different phases of its progression. Oxidative
      modification of lipids and inflammation differentially regulate the apoptotic and
      proliferative responses of vascular cells during progression of the
      atherosclerotic lesion. Bcl-2 proteins act as the major regulators of extrinsic
      and intrinsic apoptosis signalling pathways and more recently it has become
      evident that they mediate the apoptotic response of vascular cells in response to
      oxidation and inflammation either in a provocative or an inhibitory mode of
      action. Here we address Bcl-2 proteins as major therapeutic targets for the
      treatment of atherosclerosis and underscore the need for the novel preventive and
      therapeutic interventions against atherosclerosis, which should be designed in
      the light of molecular mechanisms regulating apoptosis of vascular cells in
      atherosclerotic lesions.

PMID- 16951925
TI  - An integrate-and-fire model for synchronized bursting in a network of cultured
      cortical neurons.
AB  - It has been suggested that spontaneous synchronous neuronal activity is an
      essential step in the formation of functional networks in the central nervous
      system. The key features of this type of activity consist of bursts of action
      potentials with associated spikes of elevated cytoplasmic calcium. These features
      are also observed in networks of rat cortical neurons that have been formed in
      culture. Experimental studies of these cultured networks have led to several
      hypotheses for the mechanisms underlying the observed synchronized oscillations.
      In this paper, bursting integrate-and-fire type mathematical models for regular
      spiking (RS) and intrinsic bursting (IB) neurons are introduced and incorporated
      through a small-world connection scheme into a two-dimensional excitatory network
      similar to those in the cultured network. This computer model exhibits
      spontaneous synchronous activity through mechanisms similar to those hypothesized
      for the cultured experimental networks. Traces of the membrane potential and
      cytoplasmic calcium from the model closely match those obtained from experiments.
      We also consider the impact on network behavior of the IB neurons, the geometry
      and the small world connection scheme.

PMID- 16951926
TI  - Decision-making about volitional impairment in sexually violent predators.
AB  - The Kansas v. Hendricks (1997) decision, in which the Supreme Court authorized
      post-sentence civil commitment for certain sex offenders, appeared to be
      constitutionally legitimized by limiting the class of offenders eligible for this
      special form of civil commitment to those who are "unable to control" their
      dangerousness. Nowhere in the available record, however, did the Court elucidate
      what they meant by this notion of volitional impairment. This study sought to
      examine factors that legal professionals (n=43), psychologists (n=40), and mock
      jurors (n=76) deem most relevant to a determination of sex offender volitional
      impairment. Participants, who were randomly assigned to a sexual predator
      commitment or an insanity hearing context, read a series of 16 vignettes that
      described a pedophilic offender and included combinations of variables
      hypothesized to be related to judgments of volitional impairment. Results
      suggested that participants, who as a group made remarkably high estimates of
      likelihood of future sexual violence, considered verbalization of control,
      history of sexual violence, and the context of the hearing as highly relevant to
      determinations of volitional impairment. Implications for policy and practice are
      explored.

PMID- 16951927
TI  - Identification of alpha-thalassemia mutations in subjects from Eastern Sicily
      (Italy) with abnormal hematological indices and normal Hb A2.
AB  - We analyzed the prevalence of alpha-thalassemia mutations in 298 subjects from
      Eastern Sicily (Italy) with reduced mean corpuscular volume (MCV) and mean
      corpuscular hemoglobin (MCH), normal HbA2 and HbF, and normal serum iron. In 131
      subjects (43.9%) we found six different genotypes of alpha-thalassemia: 
      alpha3.7/alphaalpha (36.6%), -alpha3.7/-alpha3.7 (27.5%), -(MED)/alphaalpha
      (10.0%), -alpha20.5/alphaalpha (9.1%), alphaHphIalpha/alphaalpha (8.4%),
      alphaHphIalpha/alphaHphIalpha (6.1%), and -alpha3.7/alphaHphIalpha (2.3%). Our
      data underline that in Eastern Sicily populations, the molecular screening of
      alpha-thalassemia mutations and/or deletions may be useful to better characterize
      the clinically asymptomatic subjects with a slightly reduced MCV and MCH and
      normal iron status.

PMID- 16951928
TI  - Absence of large molecular aggregates in X-ray contrast media.

PMID- 16951929
TI  - Screening for bone metastases: whole-body MRI using a 32-channel system versus
      dual-modality PET-CT.
AB  - The diagnostic accuracy of screening for bone metastases was evaluated using
      whole-body magnetic resonance imaging (WB-MRI) compared with combined
      fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed
      tomography (CT) (FDG-PET-CT). In a prospective, blinded study, 30 consecutive
      patients (18 female, 12 male; 24-76 years) with different oncological diseases
      and suspected skeletal metastases underwent FDG-PET-CT as well as WB-MRI with the
      use of parallel imaging (PAT). With a 32-channel scanner, coronal imaging of the
      entire body and sagittal imaging of the complete spine was performed using T1
      weighted and short tau inversion recovery (STIR) sequences in combination. PET-CT
      was conducted using a low-dose CT for attenuation correction, a PET-emission scan
      and diagnostic contrast-enhanced CT scan covering the thorax, abdomen and pelvis.
      Two radiologists read the MRI scans, another radiologist in combination with a
      nuclear medicine physician read the PET-CT scans, each in consensus. The standard
      of reference was constituted by radiological follow-up within at least 6 months.
      In 28 patients, 102 malignant and 25 benign bone lesions were detected and
      confirmed. WB-MRI showed a sensitivity of 94% (96/102), PET-CT exams achieved 78%
      (79/102; P<0.001). Specificities were 76% (19/25) for WB-MRI and 80% (20/25) for
      PET-CT (P>0.05). Diagnostic accuracy was 91% (115/127) and 78% (99/127; P<0.001),
      respectively. Cut-off size for the detection of malignant bone lesions was 2 mm
      for WB-MRI and 5 mm for PET-CT. WB-MRI revealed ten additional bone metastases
      due to the larger field of view. In conclusion, WB-MRI and FDG-PET-CT are robust
      imaging modalities for a systemic screening for metastatic bone disease. PAT
      allows WB-MRI bone marrow screening at high spatial resolution and with a
      diagnostic accuracy superior to PET-CT.

PMID- 16951930
TI  - Propagation of pacemaker activity.
AB  - Spontaneous activity of specific regions (e.g., the Sinoatrial node, SAN) is
      essential for the normal activation sequence of the heart and also serve as a
      primary means of modulating cardiac rate by sympathetic tone and circulating
      catecholamines. The mechanisms of how a small SAN region can electrically drive a
      much larger atrium, or how a small ectopic focus can drive surrounding
      ventricular or atrial tissue are complex, and involve the membrane properties and
      electrical coupling within the SAN or focus region as well as the membrane
      properties, coupling conductance magnitudes and also regional distribution within
      the surrounding tissue. We review here studies over the past few decades in which
      mathematical models and experimental studies have been used to determine some of
      the design principles of successful propagation from a pacemaking focus. These
      principles can be briefly summarized as (1) central relative uncoupling to
      protect the spontaneously firing cells from too much electrotonic inhibition, (2)
      a transitional region in which the cell type and electrical coupling change from
      the central SAN region to the peripheral atrial region, and (3) a distributed
      anisotropy to facilitate focal activity.

PMID- 16951931
TI  - Classification of surface EMG signals using optimal wavelet packet method based
      on Davies-Bouldin criterion.
AB  - In this paper we present an optimal wavelet packet (OWP) method based on Davies
      Bouldin criterion for the classification of surface electromyographic signals. To
      reduce the feature dimensionality of the outputs of the OWP decomposition, the
      principle components analysis was employed. Then we chose a neural network
      classifier to discriminate four types of prosthesis movements. The proposed
      method achieved a mean classification accuracy of 93.75%, which outperformed the
      method using the energy of wavelet packet coefficients (with mean classification
      accuracy 86.25%) and the fuzzy wavelet packet method (87.5%).

PMID- 16951932
TI  - Costimulatory molecules as immunotherapeutic targets in systemic lupus
      erythematosus.
AB  - T cells undergo full and productive activation when they traffic to lymph nodes
      where they encounter dendritic cells displaying foreign antigen in the context of
      MHC molecules on their surface. Recognition of these antigen-MHC complexes by the
      T cell's receptor for antigen, or T cell receptor, provides the first of two
      obligate signals needed to drive cell proliferation. The second antigen
      independent signal is provided by the costimulatory receptor, CD28, as it engages
      its ligand on the antigen-presenting cells. Failure of the T cell to receive this
      second signal after antigen recognition leaves the T cell in a state of anergy.
      Understanding the role of T cell costimulatory receptors in T cell activation has
      led to the development of novel approaches for regulating immune responses in
      subjects with cancer or autoimmune disease by experimentally triggering or
      blocking costimulatory receptor signaling. In this review, we will discuss,
      first, several costimulatory pathways known to participate or regulate the
      progression of autoimmune disease, and, second, how manipulation of T cell
      costimulation and/or costimulation blockade has been used to treat systemic lupus
      erythematosus.

PMID- 16951933
TI  - Idiopathic membranous nephropathy in children.
AB  - Idiopathic membranous nephropathy (MN) is a rare cause of asymptomatic
      proteinuria (AP) or nephrotic syndrome (NS) in childhood. To improve our
      understanding of its clinical course, we retrospectively reviewed 19 cases of
      idiopathic MN seen in our hospital over a period of 28.5 years, i.e., from
      January 1977 to July 2005. Eight patients (39%) had AP and 11 (61%) presented
      with NS. All eight AP patients achieved remission, regardless of treatment
      modality. Oral corticosteroid was given to all 11 NS patients, but only three of
      them responded to corticosteroid. Of the eight steroid non-responders, three
      achieved remissions with the addition of cyclosporine, and the five who were not
      administered additional immunosuppressive drugs had persistent NS. At the latest
      evaluation, all six NS patients that achieved remission remained free of
      proteinuria and had a normal renal function. Moreover, two of the 5 steroid non
      responders showed persistent nephrotic-range proteinuria but a stable renal
      function. The remaining three steroid non-responders progressed into chronic
      renal insufficiency, and this progression was preceded by renal vein thrombosis
      (RVT) in two of the three patients. Presentation with NS (P=0.045) and the
      development of RVT (P=0.010) were identified as poor prognostic factors.

PMID- 16951934
TI  - Comment on: Kalra B, Kalra S, Chatley G, Singh H (2006) rat bite as a cause of
      diabetic foot ulcer-a series of eight cases. Diabetologia 49:1452-1453.

PMID- 16951935
TI  - Comment on: Meier JJ, Lin JC, Butler AE, Galasso R, Martinez DS, Butler PC (2006)
      direct evidence of attempted beta cell regeneration in an 89-year-old patient
      with recent-onset type 1 diabetes. Diabetologia 49:1838-1844.

PMID- 16951936
TI  - Low cerebrospinal fluid insulin levels in obese humans.

PMID- 16951937
TI  - Minimally invasive treatment of pilon fractures with a low profile plate:
      preliminary results in 17 cases.
AB  - OBJECTIVE: To determine the results of "biologic fixation" with a minimally
      invasive plating technique using a newly designed low profile "Scallop" plate in
      the treatment of pilon fractures. DESIGN: Retrospective case series. SETTING: A
      tertiary referral center. PATIENTS/PARTICIPANTS: Seventeen patients were treated
      between 1999 and 2001 for a tibial plafond fracture at the Hospital for Special
      Surgery with a newly designed low-profile plate. Eleven of the fractures (65%)
      were high-energy injuries. Two fractures were open. INTERVENTION: Staged surgical
      treatment with open reduction and fixation of the fibular fracture and
      application of an external fixator was performed in 12 cases. As soon as the soft
      tissues and swelling allowed, i.e. skin wrinkling, the articular surface was
      reconstructed and simply reduced, if necessary through an small incision, and the
      articular block was fixed to the diaphysis using a medially placed,
      percutaneously introduced flat scallop plate. In the remaining five cases the
      operation was performed in one session. MAIN OUTCOME MEASUREMENTS: Time to
      healing and complications including delayed union, non-union, instrument failure,
      loss of fixation, infection, quality of reduction and number of reoperations were
      evaluated. Quality of results and outcome were graded using the ankle-hindfoot
      scale and a modified rating system. RESULTS: All patients went on to bony union
      at an average time of 14 weeks. There were no plate failures or loss of
      fixation/reduction. Two superficial wound-healing problems resolved with local
      wound care. At an average follow up of 17 months (range 6-29 months) eight
      patients (47%) had an excellent result; seven (41%) had a fair result whereas two
      (12%) had a poor result. The average ankle-hindfoot-score was 86.1 (range 61
      100). Four patients have had the hardware removed and one of them is awaiting an
      ankle arthrodesis. CONCLUSIONS: Based on these initial results, it appears that a
      minimally invasive surgical technique including new low profile plate can
      decrease soft tissue problems while leading to fracture healing and obtaining
      results comparable with other more recent series. We believe that this new
      "Scallop Plate" is effective for the treatment of pilon fractures and should be
      used in conjunction with a staged procedure in the acute trauma setting.

PMID- 16951938
TI  - Di-(2-ethylhexyl)-phthalate affects lipid profiling in fetal rat brain upon
      maternal exposure.
AB  - Lipids, especially essential fatty acids (EFAs), play critical roles in guiding
      proper fetal development. Exposure to xenobiotics that may alter the fetal supply
      of EFAs/lipids could potentially lead to fetotoxicity. In this study, we
      investigated the effects of the peroxisome proliferator chemical, di-(2
      ethylhexyl)-phthalate (DEHP), on the lipid metabolomic profile of the rat fetal
      brain upon maternal exposure during gestation. Female Sprague-Dawley rats were
      orally gavaged with a control vehicle or DEHP (1,500 mg/kg) from gestational day
      (GD) 0 to GD 19 and fetal brain tissue was isolated at GD 20. The concentrations
      of 11 lipid classes [free fatty acid, free cholesterol (FC), cholesterol ester
      (CE), diacylglycerol (DAG), triacylglyceride, phosphatidylcholine,
      phosphatidylethanolamine, phosphatidylserine (PS), lysophosphatidylcholine
      (LYPC), cardiolipin, and sphingomyelin (SM)] were determined, as well as the
      differences in the composition of individual fatty acids. The total lipid
      concentration decreased with DEHP exposure, particularly for FC and SM, by 33 and
      54%, respectively. The same trend was observed in the fatty acid compositions,
      particularly the unsaturated fatty acids, where a greater decrease was observed
      with longer fatty acid chain length. The compositions of docosahexaenoic acid
      decreased significantly in five lipid classes (P < 0.05), including CE (43%), DAG
      (60%), PS (33%), LYPC (35%), and SM (40%). In contrast, the most remarkable
      reduction of arachidonic acid presented in two lipid classes, CE and LYPC, with a
      decrease of up to 33%. These results suggest that in utero exposure to DEHP
      alters the lipid metabolome in the fetal brain, which may lead to aberrant
      neurodevelopment.

PMID- 16951939
TI  - Integrated framework of nonlinear prediction and process monitoring for complex
      biological processes.
AB  - Bioprocesses and biosystems have nonlinear and multiple operation patterns
      depending on the influent loads, temperatures, the activity of microorganisms,
      and other factors. In this paper, an integrated framework of nonlinear modeling
      and process monitoring methods is developed for a complex biological process. The
      proposed method is based on modeling by fuzzy partial least squares (FPLS) and on
      process monitoring by a statistical decomposition, which is suitable for
      predicting and supervising a nonlinear biological process. Case studies in the
      bio-simulated process and industrial biological plant show that the proposed
      method can give superior prediction and monitoring performance in complex
      biological plants compared to other linear and nonlinear methods, since it can
      effectively capture the nonlinear causal relationship within the biosystem. This
      gives us the integrated framework that is able to both model and monitor the
      nonlinear bioprocess simultaneously.

PMID- 16951940
TI  - Pyogenic liver abscess: Klebsiella as an emerging pathogen.
AB  - Patients with pyogenic liver abscesses often present to the emergency department
      with fever of unknown origin. After the appropriate clinical evaluation, cross
      sectional imaging may be performed in the emergent setting to aid in localization
      of fever source. On computed tomography imaging, pyogenic liver abscesses may
      present as inflammatory masses in the liver, with Escherichia coli as the most
      common pathogen. We report an emerging hepatic pathogen as the cause, Klebsiella
      pneumoniae.

PMID- 16951941
TI  - Effects of species and cellular activity of oviductal epithelial cells on their
      dialogue with co-cultured mouse embryos.
AB  - An efficient co-culture system, especially with oviductal or uterine epithelial
      cells, is important not only for the production of high quality embryos, but also
      for the study of the molecular dialogue between embryos and their maternal
      environment. Although mouse embryos have been co-cultured successfully with
      oviductal epithelial cells (OECs) from several species, studies on the effects of
      species and functionality of OECs are few. Reports concerning the necessity of
      direct contact between the embryo and OECs and about the culture of mouse embryos
      in medium conditioned with heterologous OECs have been controversial. In this
      study, pronuclear embryos from Kunming mice, characterized by an obvious two-cell
      block in vitro, were co-cultured with mouse, goat, and chick OECs. The
      functionality of OECs was determined by analyzing the cell cycle, apoptosis, the
      numbers of mitochondria and cilia, and the ability both to support embryonic
      development and to remove hypoxanthine from the culture medium. The necessity of
      direct contact between OECs and embryos was studied by repeated renewal of
      culture medium with fresh conditioned medium, the culture of embryos in plastic
      wells connected by tunnels to wells with OEC monolayers, and the co-culture of
      embryos separated from OECs by a filter. Both goat and chick OECs supported mouse
      embryonic development, but their embryotrophic lifespan was shorter than that of
      the mouse OECs. Whereas media conditioned with mouse OECs supported mouse
      embryonic development satisfactorily, medium conditioned with goat OECs supported
      little development. Immediate dialogue between heterologous OECs and embryos was
      essential for efficient co-culture, whereas direct contact between the two cell
      types was not; neither dialogue nor contact was needed between isologous OECs and
      embryos. Embryotrophic activity and the ability to remove hypoxanthine from
      conditioned medium declined with time after confluence and number of passages of
      OECs, mainly because of apoptosis and dedifferentiation. Thus, the species and
      functionality of OECs have profound effects on their molecular dialogue with co
      cultured embryos, and efficient co-culture depends upon both positive and
      negative conditioning.

PMID- 16951943
TI  - Tumour necrosis factor alpha promoter polymorphisms and etanercept therapy in
      juvenile idiopathic arthritis.
AB  - The objective of this study was to investigate the influence of TNF-alpha
      promoter alleles on clinical response to etanercept therapy in JIA. TNF-alpha
      promoter polymorphisms at positions -163, -238, -244, -308, -376 were determined
      in 137 JIA patients treated with etanercept for at least 3 months. A PCR fragment
      of about 500 bp of the TNF gene promoter was amplified. Polymorphisms were
      detected by a single sequencing procedure. Patients with the genotype -308GG
      achieved an ACR-JRA 30 response at month 6 more frequently than patients with the
      genotype -308GA or AA. This was already notable at month 3 of therapy. This
      difference in the total patient group is attributable to the JIA subgroup with
      rheumatoid factor negative polyarthritis. In this subgroup, patients with the 
      308GG genotype achieved an ACR-JRA 30 response more frequently than those with
      the -308GA or AA genotype (84 vs. 33% at months three, P < 0.01, 93 vs. 67% at
      months six, P < 0.05). There was no influence of the -238 TNF-alpha promoter
      alleles on clinical response. The rare alleles at position -376 or at positions 
      163 and -244 were too infrequent. There is an association between TNF gene
      promoter polymorphisms and response to etanercept in rheumatoid factor negative
      polyarticular JIA.

PMID- 16951942
TI  - [Atrial fibrillation].
AB  - Atrial fibrillation represents the arrhythmia that most frequently leads to
      hospital admission. Due to the age structure of our population and the increasing
      morbidity and comorbidity, one has to assume that this arrhythmia will reach an
      even higher prevalence. The therapeutic successes are often insufficient. First
      of all, it is important to diagnose and treat the underlying disease. Secondly,
      antiarrhythmic therapy has to be considered in symptomatic patients. In those
      patients and in the case of a persistent form, electrical cardioversion should be
      performed. Repetitive cardioversions in asymptomatic patients yield no advantage
      for mortality. Antiarrhythmic therapy consists of drugs of the classes Ia, Ic,
      and III. Concomitant anticoagulation is necessary; ASS in indicated only in
      patients without structural heart disease and lacking thromboembolic risk
      factors. If risk factors are present, effective therapy with coumarin derivatives
      is required. Therapy with ACE inhibitors and AT blockers leads to an advantage in
      patients with arterial hypertension and/or heart failure concerning the stability
      of sinus rhythm after cardioversion and the incidence of arrhythmia. Newer
      medications for anticoagulation and newer antiarrhythmic drugs raise the hope of
      a future therapy with higher efficacy and lower rate of side effects.

PMID- 16951944
TI  - Acute renal failure in a patient with familial Mediterranean fever.

PMID- 16951945
TI  - No evidence for an association between the Glu298Asp polymorphism of the
      endothelial nitric oxide synthase gene and fibromyalgia syndrome.
AB  - The objective of this study was to analyze the genotype distributions and allele
      frequencies for the Glu298Asp (G894T) polymorphism of the eNOS gene and the serum
      nitric oxide level among the patients with fibromyalgia syndrome (FS). Ninety-six
      fibromyalgia patients and 79 unrelated healthy volunteer controls were included
      in the study. All patients and controls were females. Genomic DNA from 96
      patients meeting the American College of Rheumatology 1990 criteria for FS and 79
      healthy controls was analyzed by polymerase chain reaction. A polymerase chain
      reaction-restriction fragment-length polymorphism analysis of eNOS gene
      polymorphism was performed, and the results of the patients with FS and healthy
      controls were compared. Ozone-based chemiluminescence assay with Sievers NO
      Analyzer was used to measure the serum nitric oxide levels. Neither the
      frequencies of the Glu298Asp genotypes nor the serum nitric oxide levels showed a
      significant difference between the groups. These results suggested that FS of the
      Turkish population seemed to develop without any alterations in eNOS Glu298Asp
      genotype frequency and the serum nitric oxide level.

PMID- 16951946
TI  - The oxidant-antioxidant balance in systemic sclerosis cases with interstitial
      lung involvement.
AB  - We aimed to assess the plasma oxidant and antioxidant levels in systemic
      sclerosis (SS) patients with interstitial lung involvement. Twenty-seven female
      SS patients and 17 healthy female volunteers were included in the study. Plasma
      levels of oxidants and antioxidants levels were studied of two groups. The median
      oxidant and antioxidant levels in study and control groups were, MDA 5.2 +/-
      0.4/3.7 +/- 0.5 nmol/ml (P < 0.001), NO 45.4 +/- 3.7/34.2 +/- 2.9 nmol/l (P <
      0.001), SOD 25.6 +/- 2.3/24.6 +/- 2.0 U/ml (P > 0.05), catalase 99.9 +/-
      9.9/140.0 +/- 10.0 U/ml (P < 0.001), vitamin E 20.5 +/- 1.3/22.6 +/- 2.0%mg (P <
      0.001), vitamin C 70.6 +/- 8.7/83.5 +/- 7.3 mg/dl (P < 0.001), respectively.
      There was also no correlation between plasma levels of oxidants-antioxidants
      levels and disease duration, duration of pulmonary signs, pulmonary function test
      values, HRCT scores in SS patients (P > 0.05). In our study, the oxidant burden
      in SS patients with interstitial lung involvement was found to be increased;
      however no correlation was detected between the severity of lung involvement and
      oxidant-antioxidant levels.

PMID- 16951947
TI  - Novel aminoglycosides increase SMN levels in spinal muscular atrophy fibroblasts.
AB  - Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality.
      SMA is caused by the homozygous absence of survival motor neuron-1 (SMN1). SMN2,
      a nearly identical copy gene, is retained in all SMA patients and encodes an
      identical protein as SMN1; however, SMN1 and SMN2 differ by a silent C to T
      transition which results in the production of an alternatively spliced isoform
      (SMNDelta7), which encodes a defective protein, demonstrating that the absence of
      the short peptide encoded by SMN exon 7 is critical in SMA development.
      Previously, we have shown that for some functions heterologous sequences can
      compensate for the exon 7 peptide, suggesting that the SMN C-terminus functions
      non-specifically. Consistent with this hypothesis, we now identify novel
      aminoglycosides that can induce SMN protein levels in patient fibroblasts. This
      hypothesis was supported, in part, by a novel fluorescent SMN read-through assay.
      Interestingly, however, through the development of a SMN exon 7-specific
      antibody, results suggested that levels of normal full-length SMN might also be
      elevated by aminoglycoside treatment. These results demonstrate that the
      compounds that promote read-through may provide an alternative platform for the
      discovery of compounds that induce SMN protein levels.

PMID- 16951949
TI  - Interleukin-6 response to isokinetic exercise in elite athletes: relationships to
      adrenocortical function and to mechanical and myoelectric fatigue.
AB  - Exercise stimulates the release of interleukin-6 (IL-6). Aims of the study were
      to: (a) analyse the IL-6 response to exercise in power (n = 7) and endurance
      athletes (n = 13); (b) determine the effects of the IL-6 production on mechanical
      and myoelectric fatigue; (c) evaluate the relationship between IL-6 and
      adrenocortical responses. EMG variables (conduction velocity, mean power
      frequency, average rectified value), ACTH, cortisol, DHEA, IL-6, myoglobin, and
      lactate were analysed before and after an isokinetic exercise. The exercise
      elicited significant mechanical and myoelectric fatigue as well as significant
      biochemical responses. Power athletes showed IL-6 and lactate responses higher
      than endurance athletes. The correlation analyses showed that the greater the
      mechanical fatigue, the greater the increases in lactate and IL-6. No
      correlations were found between IL-6 and EMG variables. No relationships were
      found between IL-6 and cortisol, after correction for ACTH levels. In conclusion,
      the muscular IL-6 production, as inferred by its circulating levels, had no
      detectable effects on the myoelectric manifestations of fatigue and the cortisol
      response to exercise was not related to the amount of circulating IL-6, but only
      to the activation of ACTH secretion.

PMID- 16951948
TI  - A shared Y-chromosomal heritage between Muslims and Hindus in India.
AB  - Arab forces conquered the Indus Delta region in 711 AD: and, although a Muslim
      state was established there, their influence was barely felt in the rest of South
      Asia at that time. By the end of the tenth century, Central Asian Muslims moved
      into India from the northwest and expanded throughout the subcontinent. Muslim
      communities are now the largest minority religion in India, comprising more than
      138 million people in a predominantly Hindu population of over one billion. It is
      unclear whether the Muslim expansion in India was a purely cultural phenomenon or
      had a genetic impact on the local population. To address this question from a
      male perspective, we typed eight microsatellite loci and 16 binary markers from
      the Y chromosome in 246 Muslims from Andhra Pradesh, and compared them to
      published data on 4,204 males from East Asia, Central Asia, other parts of India,
      Sri Lanka, Pakistan, Iran, the Middle East, Turkey, Egypt and Morocco. We find
      that the Muslim populations in general are genetically closer to their non-Muslim
      geographical neighbors than to other Muslims in India, and that there is a highly
      significant correlation between genetics and geography (but not religion). Our
      findings indicate that, despite the documented practice of marriage between
      Muslim men and Hindu women, Islamization in India did not involve large-scale
      replacement of Hindu Y chromosomes. The Muslim expansion in India was
      predominantly a cultural change and was not accompanied by significant gene flow,
      as seen in other places, such as China and Central Asia.

PMID- 16951950
TI  - Comparison of genetic transformation in Morus alba L. via different regeneration
      systems.
AB  - Three different regeneration systems, viz. direct regeneration of adventitious
      shoot buds from explant, regeneration through callus cultures and somatic embryos
      were compared to see their effect on transfer of neomycin phosphotransferase
      (nptII) and beta-glucuronidase (GUS) reporter gene (gus) to Morus alba clone M5,
      through Agrobacterium tumefaciens mediated transformation. Pre-conditioning and
      co-cultivation durations had a marked effect on transformation frequency. The
      highest transformation frequency of 18.6% was obtained using direct induction of
      adventitious shoot buds. Expression and presence of transgene were assayed
      histochemically and through polymerase chain reaction. Southern analysis of GUS
      and PCR positive transformants confirmed stable integration of transgenes with
      two to four copy numbers. The selected transformants showed normal phenotype
      under in vitro and field conditions.

PMID- 16951951
TI  - [Postoperative ileus. Pathophysiology and prevention].
AB  - Continuous improvements in surgical technique and anaesthesia for ileus have
      resulted in a significant reduction of perioperative complications. Postoperative
      outcome of surgical patients is increasingly dependent on the severity of
      postoperative ileus, which often determines morbidity and length of hospital
      stay. In the present article we discuss possible variables influencing this
      disease. Furthermore, means of prevention and therapeutic strategies for
      postoperative ileus are briefly presented.

PMID- 16951952
TI  - Patients and carer experiences of care provision after a diagnosis of lung cancer
      in Scotland.
AB  - INTRODUCTION: This qualitative study was set out to explore experiences of care
      provision of 60 patients diagnosed with lung cancer and a carer of their choice
      MATERIALS AND METHODS: Participants were invited to take part in three in-depth
      interviews over a 6-month period. After considerable sample attrition due to
      worsening disease or death over the study period, 23 complete patient data sets
      were available for analysis. Fifteen complete carer data sets were analysed.
      RESULTS: Four key domains of need were identified: (1) the pathway to
      confirmation of diagnosis, (2) communication of diagnosis, treatment options and
      prognosis, (3) provision of co-ordinated, family-oriented care and (4) support
      away from acute services. Discernable shifts in patients' needs were apparent
      over time within and across the four domains, illustrating a complex relationship
      between the categories of need experienced by patients and carers. DISCUSSION:
      Around the time of diagnosis, the priorities of patients and carers centred
      around their needs for information about the process of treatment and the options
      open to them. As time went on, they appeared to experience feelings of greater
      isolation and physical dependency and were particularly aware of deficiencies in
      the coordination of supportive care. Many patients appeared to rely on the
      relationship they had developed with their hospital consultant and, therefore,
      found it difficult to make the transition into palliative care or at least a more
      primary-care-led service once treatment was over. CONCLUSION: Data from the study
      point to the importance of heightening general practitioner awareness of
      potential signs and symptoms of lung cancer. Findings indicate the need to
      evaluate the benefits to patients and carers of rapid access to diagnostic tests
      and results and support the establishment of effective and streamlined supportive
      care pathways for patients with lung cancer.

PMID- 16951953
TI  - Basal and hyperaemic myocardial blood flow in regionally denervated canine
      hearts: an in vivo study with positron emission tomography.
AB  - PURPOSE: Positron emission tomography (PET) studies in patients with diabetic
      autonomic neuropathy (DAN) have demonstrated the impact of this disease on
      cardiac sympathetic innervation and myocardial blood flow (MBF). To investigate
      the effects of selective partial sympathetic denervation of the left ventricle
      (LV) on baseline and hyperaemic MBF, we measured myocardial presynaptic
      catecholamine re-uptake (uptake-1), beta-adrenoceptor (beta-AR) density and MBF
      non-invasively by means of PET in a canine model of regional sympathetic
      denervation. METHODS: In 11 anaesthetised dogs, the sympathetic nerves of the
      free wall and septum of the LV were removed by means of dissection and phenol
      painting. Three weeks later, the animals were studied with PET. MBF was measured
      at baseline and following i.v. adenosine (140 microg kg(-1) min(-1)) and
      dobutamine (20 microg kg(-1) min(-1)) using(15)O-labelled water. Sympathetic
      denervation was confirmed by an 80+/-12% decrease in the volume of distribution
      (V(d)) of [(11)C]hydroxyephedrine (HED) compared with innervated regions.
      Myocardial beta-AR density was measured using [(11)C]CGP12177. RESULTS:
      Innervated and denervated regions showed no differences in MBF at baseline and
      during adenosine or dobutamine. [(11)C]HED V(d)was inversely correlated with MBF
      in both regions at baseline, and the correlation was lost during hyperaemia in
      denervated regions. However, for any given value of MBF, [(11)C]HED V(d)was
      significantly lower in the denervated regions. beta-AR density was comparable in
      denervated and innervated regions (17.9+/-4.2 vs 18.4+/-3.3 pmol g(-1); p=NS).
      CONCLUSION: In this experimental model, selective, regional sympathetic
      denervation of the LV, which results in a profound reduction in [(11)C]HED V(d),
      did not affect baseline or hyperaemic MBF. In addition, we demonstrated that,
      under baseline conditions, there was a significant inverse correlation between
      [(11)C]HED V(d)and MBF in both denervated and innervated regions.

PMID- 16951954
TI  - Sixty-four slice spiral CT angiography does not predict the functional relevance
      of coronary artery stenoses in patients with stable angina.
AB  - PURPOSE: The aim of this study was to evaluate spiral multidetector computed
      tomography (MDCT) angiography using 64-slice technique in the detection of
      functionally relevant coronary artery stenoses (CAS). METHODS: Thirty-eight
      patients (62+/-11 years, 28 men) with stable angina (26 with suspected and 12
      with known coronary artery disease) were investigated using 64-slice MDCT
      angiography and gated myocardial perfusion SPECT (gated SPECT); a subgroup of 30
      patients had additional invasive coronary angiography (ICA). Stenoses with
      luminal narrowing of >or=50% were defined as "significant" in MDCT angiography
      and ICA. MDCT angiography was compared with gated SPECT and the combination of
      gated SPECT plus ICA with respect to the detection of functionally relevant CAS.
      RESULTS: The sensitivity, specificity and negative and positive predictive values
      of MDCT angiography in detecting reversible perfusion defects on gated SPECT were
      63%, 80%, 94% and 32%, respectively, in vessel-based analysis and 71%, 62%, 72%
      and 60%, respectively, in patient-based analysis. If only reversible perfusion
      defects on gated SPECT with CAS >or=50% on ICA were considered, the sensitivity,
      specificity and negative and positive predictive values were, respectively, 85%,
      79%, 98% and 33% for vessel-based analysis and 85%, 59%, 83% and 61% for patient
      based analysis. CONCLUSION: Sixty-four slice MDCT angiography failed to predict
      the functional relevance of CAS, but had a high negative predictive value in the
      exclusion of functionally relevant CAS in symptomatic patients.

PMID- 16951955
TI  - Changing paradigm: atherosclerosis versus ischaemia.

PMID- 16951956
TI  - Clinical effect of radiation synovectomy of the upper extremity joints: a
      randomised, double-blind, placebo-controlled study.
AB  - PURPOSE: To compare the clinical efficacy of radiosynoviorthesis (RSO) with intra
      articular radionuclide plus glucocorticoid (GC) injection (group A) with that of
      placebo plus GC injection (group B) for the treatment of persistent synovitis in
      joints of the upper extremity. METHODS: At baseline and at 6 and 12 months after
      intra-articular injection, six clinical parameters were scored. Changes in
      clinical values over time were summed to provide a change composite index (CCI),
      ranging from 0 (no effect) to 12 (maximal effect). A CCI > or =6 was considered
      to indicate successful treatment. Differences in response rate and CCI between
      groups A and B were examined. Regression analyses were performed to explore
      whether baseline variables could predict therapeutic effect. RESULTS: Sixty-eight
      joints in 44 patients were treated. Six months after intra-articular injection,
      response rates (CCI > or =6) were 69% (25/36) in group A and 29% (9/31) in group
      B (p=0.001). The mean CCIs +/- standard deviation at 6 months were 6.7+/-3.2 for
      group A and 3.3+/-3.8 for group B (p=0.001). At 12 months the response rates were
      69% (25/36) in group A and 32% (8/25) in group B (p=0.004). The mean CCIs at 12
      months were 6.8+/-3.3 for group A and 4.2+/-4.7 for group B (p= 0.046). None of
      the baseline variables predicted the therapeutic effect. CONCLUSION: RSO
      (radionuclide plus GC) of upper extremity joints with immobilisation for 72 h
      shows a significantly better response rate than placebo plus GC in patients with
      persistent synovitis after at least one failed outpatient intra-articular GC
      injection.

PMID- 16951957
TI  - Functional asymmetries in the stepping response of the human newborn: a kinematic
      approach.
AB  - In order to investigate subtle expressions of functional asymmetries in newborn
      leg movements, kinematic registrations were made on a sample of 40 healthy
      fullterm newborn infants during performance of the stepping response. Time
      position data were collected from markers attached to the hip, knee and ankle
      joints of the left and right leg, and movements of both legs recorded
      simultaneously. Findings included evident side differences in terms of smoother
      trajectories of the right leg as a consequence of less movement segmentation
      compared to the left leg. Additionally, analyses of intralimb coordination
      revealed side differences with regard to stronger ankle-knee couplings and
      smaller phase shifts in the right leg. The findings suggest that asymmetries in
      newborn stepping responses are present in terms of spatio-temporal parameters and
      intralimb coordination. No evidence of a lateral preference in terms of frequency
      of the first foot moved was found. The present study adds new understanding to
      the lateralized attributes of the stepping response in the human newborn and as
      such points to new directions of research on the nature of laterality in the
      future.

PMID- 16951958
TI  - Modulation of heat evoked nociceptive withdrawal reflexes by painful
      intramuscular conditioning stimulation.
AB  - Convergence between cutaneous heat nociceptors and muscles afferents was
      investigated by applying a phasic, conditioning electrical stimulus to the
      tibialis anterior muscle (a train of five 1 ms pulses over 21 ms) at varying time
      intervals relative to a thermal test stimulus used for evoking the withdrawal
      reflex in humans. The 200 ms thermal stimulus was applied on the dorsum of the
      foot at an intensity of two times the pain threshold. The conditioning electrical
      stimulus was applied at an intensity of two times the pain threshold via a set of
      intramuscular needle electrodes. The conditioning-test interval was varied
      between -400 ms and 8,000 ms at 17 different intervals. The mean reflex onset
      latency of reflexes evoked by thermal stimuli alone was 354 +/- 9 ms. A
      facilitation of the reflex was seen when the conditioning stimulus was applied
      275 ms (174 +/- 30% compared to control) and 300 ms (162 +/- 32% compared to
      control) after the test stimulus onset indicating sensory convergence between
      muscle afferents (group I-III) and cutaneous Adelta heat nociceptors arriving
      simultaneously at the spinal cord.

PMID- 16951959
TI  - Visual oddballs induce prolonged microsaccadic inhibition.
AB  - Eyes never stop moving. Even when asked to maintain the eyes at fixation, the
      oculomotor system produces small and rapid eye movements called microsaccades, at
      a frequency of about 1.5-2 s(-1). The frequency of microsaccades changes when a
      stimulus is presented in the visual field, showing a stereotyped response pattern
      consisting of an early inhibition of microsaccades followed by a rebound, before
      the baseline is reached again. Although this pattern of response has generally
      been considered as a sort of oculomotor reflex, directional biases in
      microsaccades have been recently linked to the orienting of spatial attention. In
      the present study, we show for the first time that regardless of any spatial
      bias, the pattern of absolute microsaccadic frequency is different for oddball
      stimuli compared to that elicited by standard stimuli. In a visual-oddball task,
      the oddball stimuli caused an initial prolonged inhibition of microsaccades,
      particularly when oddballs had to be explicitly recognized and remembered. The
      present findings suggest that high-order cognitive processes, other than spatial
      attention, can influence the frequency of microsaccades. Finally, we also
      introduce a new method for exploring the visual system response to oddball
      stimuli.

PMID- 16951960
TI  - Independent roles for the dorsal paraflocculus and vermal lobule VII of the
      cerebellum in visuomotor coordination.
AB  - Two distinct areas of cerebellar cortex, vermal lobule VII and the dorsal
      paraflocculus (DPFl) receive visual input. To help understand the visuomotor
      functions of these two regions, we compared their afferent and efferent
      connections using the tracers wheatgerm agglutinin horseradish peroxidase (WGA
      HRP) and biotinilated dextran amine (BDA). The sources of both mossy fibre and
      climbing fibre input to the two areas are different. The main mossy fibre input
      to lobule VII is from the nucleus reticularis tegmenti pontis (NRTP), which
      relays visual information from the superior colliculus, while the main mossy
      fibre input to the DPFl is from the pontine nuclei, relaying information from
      cortical visual areas. The DPFl and lobule VII both also receive mossy fibre
      input from several common brainstem regions, but from different subsets of cells.
      These include visual input from the dorsolateral pons, and vestibular-oculomotor
      input from the medial vestibular nucleus (MVe) and the nucleus prepositus
      hypoglossi (Nph). The climbing fibre input to the two cerebellar regions is from
      different subdivisions of the inferior olivary nuclei. Climbing fibres from the
      caudal medial accessory olive (cMAO) project to lobule VII, while the rostral MAO
      (rMAO) and the principal olive (PO) project to the DPFl. The efferent projections
      from lobule VII and the DPF1 are to all of the recognised oculomotor and visual
      areas within the deep cerebellar nuclei, but to separate territories. Both
      regions play a role in eye movement control. The DPFl may also have a role in
      visually guided reaching.

PMID- 16951961
TI  - Modulation of intracortical facilitatory circuits of the human primary motor
      cortex by digital nerve stimulation.
AB  - We investigated the effect of electrical digit stimulation on two different
      intracortical facilitatory phenomena. Paired-pulse transcranial magnetic stimuli
      (TMS) with different conditioning stimulus (CS) intensities were applied over the
      primary motor cortex (M1). Electromyographic (EMG) recordings were made from the
      relaxed right abductor digiti minimi muscle (ADM). The effect of preceding
      sensory stimulation applied to the ipsilateral digit V on the conditioning
      magnetic stimulus was examined. Changing the CS intensity affected the influence
      of peripheral electrical stimulation on motor evoked potential (MEP) amplitudes
      evoked by paired pulse TMS. Inhibition induced by ipsilateral digit stimulation
      was strongest with the lowest CS intensity if MEP amplitudes were evoked by a
      subthreshold CS followed by a suprathreshold test stimulus (TS) at an
      interstimulus interval (ISI) of 10 ms. In contrast, inhibition induced by digit
      stimulation in a paired-pulse paradigm with a suprathreshold first and a
      subthreshold second stimulus at ISI of 1.5 ms was strongest with the highest CS
      intensity. These findings suggest that appropriately timed peripheral electrical
      stimuli differentially modulate facilitatory interactions in the primary motor
      cortex. They further support the hypothesis that intracortical facilitation (ICF)
      and short-interval intracortical facilitation (SICF) are evoked through different
      mechanisms.

PMID- 16951962
TI  - Staged operations for posthemorrhagic hydrocephalus in extremely low-birth-weight
      infants with preceding stoma creation after bowel perforation: surgical strategy.
AB  - CASE REPORT: We report a complicated extremely low-birth-weight (ELBW) infant
      with posthemorrhagic hydrocephalus after intraventricular hemorrhage and
      preceding stoma creation after bowel perforation who was treated with staged
      operations, including shunting and external ventricular drainage. The first
      operation was a temporary valveless ventriculoperitoneal (VP) shunt placement
      until the time of the stoma closure. The stoma was successfully closed 3 months
      after the first operation when the peritoneal tube was drawn out from the chest
      wall and the VP shunt system was temporarily used as an external drainage with a
      long subcutaneous tunnel. One month after the second operation, final VP shunt
      placement was performed after good healing of bowel anastomosis was surely
      confirmed. The previous peritoneal shunt tube was cut behind the ear, removed,
      and replaced with a valve-regulated VP shunt system. CONCLUSION: This staged
      strategy is a safe and feasible option for complicated ELBW infants with
      preceding stoma and hydrocephalus.

PMID- 16951963
TI  - Age dependence of fusion of primary occipital sutures: a radiographic study.
AB  - PURPOSE: When linear lucency is present in the occipital bone on radiographs
      throughout childhood, differential diagnosis becomes important because some
      primary sutures are similar to fractures. The authors here chronicled the normal
      development of ossification centers, sutures, and synchondroses in the
      chondrocranium by radiographic examination. METHODS: One hundred and twenty-seven
      children, aged from newborns to 6 years and without any skull base deformities,
      were referred to for radiographs of Towne's projection. RESULTS: In the occipital
      bone at birth, three primary sutures could be identified. At the age of 0-3
      years, occipital and innominate sutures started to fuse, this being complete by 4
      years, whereas mendosal sutures persisted until 6 years of age, after which no
      primary sutures could be seen. CONCLUSION: The complex process of skull base
      development features a step-wise process sutural closure for which radiographic
      standards allow differential diagnosis from fractures with judgment of the
      timing.

PMID- 16951965
TI  - Thalamic gliomas in children: an extensive clinical, neuroradiological and
      pathological study of 14 cases.
AB  - OBJECT: Thalamic tumors represent only 1 to 5% of brain neoplasms but frequently
      affect children. However, pediatric series are rare and go back to several years
      in spite of recent advances in the neuroradiological, pathological, and molecular
      fields. METHODS: We report a series of 14 pediatric thalamic gliomas with
      clinical, neuroradiological, and pathological studies including p53
      immunostaining in 11 cases and 1p19q status in three cases. RESULTS: Our series
      included five pilocytic astrocytomas, seven oligodendrogliomas, and two
      glioblastomas. Pilocytic astrocytomas were characterized by strong contrast
      enhancement, lack of p53 expression, and excellent prognosis. Oligodendrogliomas
      frequently demonstrated an aspect of unilateral thalamic enlargement lacking or
      with slight contrast enhancement. Some of them expressed p53 or demonstrated 1p
      loss. Anaplastic oligodendrogliomas and glioblastomas displayed a poor outcome,
      with a mean survival of 8 months after surgery. CONCLUSION: Our series of
      pediatric thalamic gliomas clearly distinguishes pilocytic astrocytomas from
      anaplastic oligodendrogliomas regarding neuroimaging, pathology, and prognosis.

PMID- 16951966
TI  - Intrathecal aspergillosis and fusiform arterial aneurysms in an immunocompromised
      child: a clinico-pathological case report.
AB  - CASE REPORT: We describe a 12-year-old boy with subarachnoid hemorrhage. Cerebral
      angiography revealed multiple fusiform intracranial arterial aneurysms. Surgical
      therapy other than ventricular drainage was not feasible due to the extent and
      pattern of pathological changes. Aspergillus antigen was found in the
      cerebrospinal fluid (CSF). However, cultures of urine, CSF, and samples from the
      upper airways were negative for Aspergillus and other fungi. The boy was
      immunocompromised due to prophylactic antibiotic therapy for recurrent pneumonia
      and continuous steroid therapy for his hemolytic anemia. There were Aspergillus
      antigens but no evidence of ongoing infection with the fungus was found. The
      patient suffered recurrent intraventricular hemorrhage and died on the 31st day
      after admission. PATHOLOGICAL EXAMINATION: Pathological examination showed
      multiple fusiform aneurysms, hypertrophy of the intima, and destruction of the
      internal elastic membrane of the cerebral arteries. No fungus infiltration was
      detected. We speculate that the patient had previously had an Aspergillus
      infection, causing segmental destruction of the internal elastic membrane.
      However, we cannot rule out noninfectious vasculitis as possible etiology.
      CONCLUSIONS: In the immunocompromised child, fusiform segmental intracranial
      arterial aneurysms may be secondary to the destruction of the internal elastic
      membrane by fungus infection. The condition may present with aneurysm rupture and
      subarachnoid hemorrhage. In this patient group, surgical therapy is rarely an
      option and the prognosis is poor.

PMID- 16951964
TI  - Current concepts in the molecular genetics of pediatric brain tumors:
      implications for emerging therapies.
AB  - BACKGROUND: The revolution in molecular biology that has taken place over the
      past 2 decades has provided researchers with new and powerful tools for detailed
      study of the molecular mechanisms giving rise to the spectrum of pediatric brain
      tumors. Application of these tools has greatly advanced our understanding of the
      molecular pathogenesis of these lesions. REVIEW: After familiarizing readers with
      some promising new techniques in the field of oncogenomics, this review will
      present the current state of knowledge as it pertains to the molecular biology of
      pediatric brain neoplasms. Along the way, we hope to highlight specific instances
      where the detailed mechanistic knowledge acquired thus far may be exploited for
      therapeutic advantage.

PMID- 16951967
TI  - Qualitative and quantitative evaluation of total and types I and III collagens in
      patients with ventral hernias.
AB  - AIM: The purpose of this study was to evaluate the amount of total and types I
      and III collagens of samples from the linea alba in patients with hernias
      (epigastric, umbilical, and incisional) on the anterior wall of the abdomen,
      comparing them to findings obtained from a cadaver control group without hernias.
      MATERIALS AND METHODS: Samples of the linea alba aponeurosis from 26 patients
      with hernias on the anterior abdominal wall and from 32 cadavers without hernias
      were analyzed and compared for qualitative and quantitative evaluation of the
      total and the types I and III collagens. Sirius-red staining was used to evaluate
      the total collagen, and for types I and III collagens, immunohistochemistry was
      used with monoclonal antibody anticollagen types I and III, respectively.
      RESULTS: The amount of total collagen was 18.05% smaller in patients with hernias
      than in cadavers (p<0.05). Type I collagen was 20.50% smaller in patients than in
      cadavers (p<0.05). There was no significant difference in the amount of type III
      collagen between cases and controls (p=0.383). CONCLUSION: The results of this
      study indicate a relationship between hernias of the anterior abdominal wall and
      smaller amounts of total and type I collagens.

PMID- 16951968
TI  - Biocompatibility of bacterial contaminated prosthetic meshes and porcine dermal
      collagen used to repair abdominal wall defects.
AB  - BACKGROUND AND AIMS: A contaminated or infected surgical site is considered a
      contraindication for the use of the nonabsorbable alloplastic materials employed
      to repair abdominal wall defects. Therefore, the biocompatibility of new
      prosthetic materials was investigated. MATERIALS AND METHODS: Meshes measuring
      1.5x1.5 cm made of conventional and titanium-coated polypropylene, polyglycol, or
      porcine dermal collagen were implanted under the abdominal wall of 96 rats (eight
      groups of 12 animals each) employing the inlay technique. Implantation of all
      four materials was performed both under semisterile conditions and bacterial
      contamination of the mesh. The meshes were explanted after 28 days. RESULTS: All
      the materials implanted under semisterile conditions were incorporated into the
      abdominal wall with only few intraabdominal adhesions (mean adhesion scores: 1.0,
      1.2, 1.0, 0.8 points, respectively, not significant). With the porcine dermal
      collagen, proliferation rate and the proportion of inflammatory cells were
      statistically lower (p<0.01). In the bacterial contamination group, all meshes
      were associated with a suppurating infection and strong adhesions between the
      bowel and mesh, which were most prominent in the case of dermal collagen (mean
      adhesion scores: 1.6, 1.7, 1.7, and 1.9 points, respectively, not significant).
      In this group, two animals died of peritonitis. In comparison with the other
      materials, the proliferation rate was significantly elevated (p=0.03). No
      significant differences were seen between the other materials employed.
      CONCLUSION: Irrespective of the material employed, implantation of alloplastic
      meshes in an abdominal wall contaminated with bacteria, is associated with
      suppurating infections, in particular in the case of the membrane-like porcine
      dermal collagen. Nonabsorbable alloplastic meshes and dermal skin grafts should
      therefore not be used to repair infected abdominal wall defects.

PMID- 16951969
TI  - Inadvertent parathyroidectomy during thyroid surgery: the incidence of a
      complication of thyroidectomy.
AB  - BACKGROUND AND AIMS: Incidental parathyroidectomy is a complication of thyroid
      surgery. The aim of this report is to explore the incidence, risk factors, and
      clinical relevance of inadvertent parathyroidectomy during thyroidectomy.
      MATERIALS AND METHODS: Patients who underwent thyroidectomy between January 1998
      and June 2005 were evaluated. Pathology reports were reviewed for the presence of
      parathyroid tissue in the thyroidectomy specimens. Information regarding
      diagnosis, operative details, and postoperative hypocalcemia were collected.
      RESULTS: Three hundred and fifteen thyroid procedures were performed: 163 total
      thyroidectomies, 124 near-total thyroidectomies, and 28 lobectomies. The findings
      were benign in 240 and malignant in 75 cases. Incidental parathyroidectomy was
      found in 68 (21.6%) cases: 58 were benign and 10 were malignant. One and two
      parathyroids were accidentally removed in 46 and 22 patients, respectively.
      Parathyroid tissue was found in intrathyroidal (33%) and extracapsular (27%)
      sites. Total/near-total thyroidectomy was not associated with increased risk of
      incidental parathyroidectomy (P=0.646), and there was no association of
      inadvertent parathyroidectomy with postoperative hypocalcemia (P=0.859). Thyroid
      malignancy was associated with decreased incidence of incidental
      parathyroidectomy (P=0.047). CONCLUSION: Inadvertent parathyroidectomy, although
      not uncommon, is not associated with postoperative hypocalcemia. The type of
      surgical procedure does not increase the risk of incidental parathyroidectomy,
      while thyroid malignancy may reduce the incidence of inadvertent
      parathyroidectomy.

PMID- 16951970
TI  - Incisional hernia: challenge of re-operations after mesh repair.
AB  - BACKGROUND AND AIMS: The widespread use of meshes for the repair of incisional
      hernia is currently followed by an increasing number of re-operations. The
      incidence of incisional hernia recurrence after mesh repair varies between 3 and
      32%. The problem of mesh failure and options for another surgical intervention
      seem rather unattended. METHODS: We present our experience of 77 re-operations
      after previous mesh repair that were performed between 1995 and 2004 out of a
      total of 1,070 operations for incisional hernia. The retrospective analysis
      focused on recurrence in relation to location, material of the previous mesh
      repair and the surgical procedure to resolve the problem. RESULTS: The locations
      of the preceding meshes were epifascial as onlays (n=23), retromuscular as
      sublays (n=46), within the defect as inlays (n=6) or intraperitoneally (n=2). The
      direction of the incision was vertical medial (n=41) or horizontal crossing the
      linea semilunaris (n=36). Recurrences after median incisional hernia mesh repair
      mainly occurred at the cranial border of the mesh subxiphoidal. Except for two
      patients, all recurrences manifested at the margin of the enclosed mesh.
      CONCLUSIONS: Re-operation after previous mesh repair is a surgical challenge. The
      type of revision procedure has to consider the position and material of the
      previous mesh. In our clinic recurrences, heavyweight polypropylene meshes were
      mostly treated with mesh exchange and lightweight polypropylene meshes could be
      treated by extension with a second mesh. In contrast to suture techniques,
      deficient mesh repairs are more evidently related to technical problems.

PMID- 16951971
TI  - A generalized model of the repressilator.
AB  - The repressilator is a regulatory cycle of n genes where each gene represses its
      successor in the cycle: [see text]. The system is modelled by ODEs for an
      arbitrary number of identical genes and arbitrarily strong repressor binding. A
      detailed mathematical analysis of the dynamical behavior is provided for two
      model systems: (i) a repressilator with leaky transcription and single-step
      cooperative repressor binding, and (ii) a repressilator with auto-activation and
      cooperative regulator binding. Genes are assumed to be present in constant
      amounts, transcription and translation are modelled by single-step kinetics, and
      mRNAs as well as proteins are assumed to be degraded by first order reactions.
      Several dynamical patterns are observed: multiple steady states, periodic and
      aperiodic oscillations corresponding to limit cycles and heteroclinic cycles,
      respectively. The results of computer simulations are complemented by a detailed
      and complete stability analysis of all equilibria and of the heteroclinic cycle.

PMID- 16951972
TI  - High tibial osteotomy and external fixator.

PMID- 16951973
TI  - Tunnel placement in anterior cruciate ligament (ACL) reconstruction: quality
      control in a teaching hospital.
AB  - Correct placement of the femoral and tibial bone tunnels is decisive for a
      successful anterior cruciate ligament (ACL) reconstruction. Our method of tunnel
      placement was evaluated as part of quality control at a teaching hospital. The
      emphasis was placed mainly on investigating the influence of surgical experience
      on tunnel placement, and the effect of tunnel position on the clinical outcome.
      Seventeen surgeons with different levels of experience (between 0 and >150 ACL
      reconstructions) performed endoscopic ACL repair in uniform technique from August
      2000 to August 2003 on 50 patients (18 women, 32 men, age range 18-43 years). The
      patients were available to clinical and radiological follow-up after an average
      of 19 months. The clinical outcome was classified according to the International
      Knee Documentation Committee (IKDC) standard evaluation form. The femoral tunnel
      was evaluated according to the quadrant method of Bernard and Hertel; the
      position of the tibial bone tunnel was assessed according to the criteria of
      Staubli and Rauschnig. The IKDC score revealed 47 (94%) patients with a normal
      (A) or nearly normal (B) knee joint at follow-up. According to the quadrant
      method, the femoral canal was situated on average at 29% in the saggital plane.
      The tibial tunnel was situated on average at 43% of the a.p. diameter of the
      tibial condyle. Statistical analysis of our data showed no significant
      correlation between tunnel placement and surgical expertise. However, a highly
      significant correlation was found (alpha<0.01) between the femoral position of
      the tunnel in the sagittal plane and the IKDC score. The more anterior the
      femoral canal, the poorer the IKDC score. The method of tunnel placement in ACL
      reconstruction being investigated here only showed slight dependence on surgical
      experience, whereby good short-term clinical outcomes were achieved. Therefore,
      the method is suitable for application at a teaching hospital. A far too anterior
      femoral tunnel placement will probably lead to a decline in the clinical result.

PMID- 16951974
TI  - The course of the patellar tendon after reharvesting its central third for ACL
      revision surgery: a long-term clinical and radiographic study.
AB  - The choice of the optimal graft for anterior cruciate ligament (ACL) revision
      surgery is still controversial. Reharvesting the patellar tendon has been
      suggested as one graft alternative. Our hypothesis was that in the long-term, ACL
      revision surgery using reharvested patellar tendon autografts would render a good
      clinical outcome and a normal patellar tendon at the donor site as seen on
      magnetic resonance imaging (MRI). Fourteen consecutive patients (five women, nine
      men), who underwent ACL revision surgery using reharvested ipsilateral patellar
      tendon grafts, were included in the study. They underwent bilateral MRI
      evaluations of the patellar tendon and were tested for clinical outcome 26 (20
      35) and 115 months (102-127) after the revision procedure. On the second
      occasion, they also underwent standard weight-bearing X-ray examinations. The
      serial MRI evaluations revealed that the thickness of the patellar tendon at the
      donor site was significantly increased compared with the non-harvested, normal
      contralateral side and that the donor-site gap was still visible after 10 years.
      No significant differences were seen between the 2- and 10-year MRI evaluations.
      Standard weight-bearing X-ray examinations revealed signs of mild degenerative
      changes in all patients. Clinical results in terms of the Lysholm score, IKDC
      evaluation system, one-leg-hop test, KT-1000 laxity test and the knee-walking
      test revealed no significant differences between the 2- and 10-year assessments.
      In overall terms, the clinical results were considered to be poor on both
      occasions. The patellar tendon at the donor site had not normalised 10 years
      after the reharvesting procedure, as seen on MRI. Furthermore, the clinical
      results were poor after ACL revision surgery using reharvested patellar tendon
      autograft.

PMID- 16951975
TI  - Arthroscopic assisted reduction and fixation of a juvenile Tillaux fracture.
AB  - We report a case of Tillaux fracture of the distal tibia in a 14-year-old
      patient. Reduction and fixation of the fracture was achieved arthroscopically
      through the anterolateral portal. The patient was able to participate in
      competitive athletic activities 3.5 months after surgery with an AOFAS score of
      100. Arthroscopy is an expedient tool in the management of intra-articular
      fractures of the ankle providing anatomical reduction under direct visualization
      with minimum intervention.

PMID- 16951976
TI  - Herodicus, the father of sports medicine.
AB  - Herodicus (fifth century BC: ) is the first person in the history of medicine who
      actually combined sports with medicine. He used to be a sports teacher, who later
      studied medicine and managed to succeed Euryphon in the medical school of Cnidos,
      one of the most prominent in ancient Greece together with its neighbor medical
      school of Cos (Hippocrates' home). In Cnidos Herodicus formed his own theoretical
      perspective of medicine. He considered, namely, bad health to be the result of
      imbalance between diet and physical activity and for this reason he recommended
      strict diet, constant physical activity and regular training. He believed that
      this combination was the ideal way to maintain good standards of health and he
      applied this type of treatment method to his patients. Unfortunately, Herodicus'
      works are lost today. However, excerpts of his medical system, which can be
      traced in ancient texts, support the fact that Herodicus can be considered as the
      father of sports medicine.

PMID- 16951977
TI  - Cartilage viability after trochleoplasty.
AB  - Trochleoplasty is an established and accepted technique for the treatment of
      patellar instability because of a missing trochlear groove. In this technique, a
      flap of cartilage over the trochlea is carefully removed and a new trochlear
      groove is created in the underlying bone before the cartilaginous flap is
      reattached with sutures. The mid-term clinical and radiological results of this
      operation are promising but no information about the viability of the reattached
      cartilage has been reported. To evaluate cartilage viability and quality after
      trochleoplasty and to verify the healing process, two osteochondral biopsies were
      harvested from three patients 6, 8, and 9 months after trochleoplasty. One
      cylinder was evaluated histologically to assess cartilage, calcified cartilage
      (cc), and subchondral bone quality, while the other one was examined by confocal
      microscopy to evaluate cell viability. The histological examination showed a
      normal matrix and cell distribution of the cartilage, while the cc showed lacunae
      ingrowing from the underlying bone. The subchondral bone showed normal lamellae
      and histology, and the healing of the flap. Confocal microscopy showed almost
      exclusively viable chondrocytes. This demonstration of non-injured cartilage at
      short-term follow-up together with promising clinical and radiological 2- and 5
      year follow-up results indicate a potential promising outlook for the long term,
      as further chondral damage is not expected. So trochleoplasty can be seen as a
      primary intervention for patellar instability because of trochlear dysplasia as
      the risk for cartilage damage is low.

PMID- 16951978
TI  - Bilateral, simultaneous rupture of the quadriceps tendon: a diagnostic pitfall?
      Report of three cases and meta-analysis of the literature.
AB  - Bilateral, simultaneous quadriceps tendon rupture (QTR) represents a rare entity
      and delay in establishing the correct diagnosis is not uncommon. Another three
      cases are reported here and in all the correct diagnosis was missed initially. A
      review of the English and German literature retrieved 105 cases of bilateral,
      simultaneous QTR and in 32 patients (30.5%) the correct diagnosis was established
      with delay. In 28 cases--representing 25 men (89.3%) and 3 women (10.7%)-
      sufficient data was available for further analysis. In the majority of patients
      (n = 19/28; 67.9%) rupture was associated with trauma, while no trauma was
      reported in 9/28 cases (32.1%). No direct correlation between age and the kind of
      rupture form (traumatic/spontaneous) could be detected (P = 0.35). Most partients
      (n = 18/28; 64.3%) presented risk factors associated with QTR and obesity (n =
      6/28; 21.4%) was most frequently encountered. A direct association between the
      rate of risk factors and the rupture form was not seen (P = 0.5). Overall
      diagnostic delay lasted 64.7 days on an average (traumatic ruptures 67.7
      days/spontaneous ruptures 58.7 days) with this period being longer than 2 weeks
      in 51.9% and longer than 3 months in 33.3% of patients. Delay varied distinctly
      in different medical institutions as this period lasted in hospital departments
      93.9 days, in ambulances 24 days and in General Practitioners 7.6 days on an
      average. Initially 25 incorrect diagnoses were established in 21/28 (75%)
      patients, while 7/28 cases (25%) were discharged initially without any diagnosis.
      Clinical examination revealed most often palpable suprapatellar gaps (n = 17/24)
      and effusions (n = 13/24), while the classic trias of painful swelling,
      suprapatellar gap and loss of knee extension was found in only 58.3% of reported
      patients (n = 14/24). The correct diagnosis of bilateral QTR was established in
      60.7% (n = 17/28) by history and clinical examination alone. In 10.7% (n = 3/28)
      clinical suspect was supported by sonography and in 14.3% (n = 4/28) by MRT; in
      14.3% (n = 4/28) the correct diagnosis represented a by chance finding during
      diagnostic or operative procedures of other indication. In 52 tendons detailed
      information about repair was provided and most often transosseous fixation (n =
      30/52; 57.7%) and direct repair (n = 14/52; 26.9%) were used, while a tenoplasty
      was performed in only 15.4% (n = 8/52). Only 34.6% of patients (n = 9/26) with
      follow-up data (n = 26/28) reported a full recovery with a trend that early
      surgical repair (limit 2 weeks) improves the final outcome.

PMID- 16951979
TI  - Gerdy tubercle osteotomy in surgical approach of posterolateral corner of the
      knee.
AB  - Posterolateral corner (PLC) injuries of the knee are uncommon injury patterns
      that may result in significant degrees of functional disability. When surgery is
      necessary to address this injury a good knowledge of anatomy and a good surgical
      exposure is the mainstay. This report reviews the complex anatomy of the
      posterolateral corner (PLC) of knee and describes the osteotomy of Gerdy tubercle
      as a technical variant to approach this anatomical region. This surgical step
      allowing a good mobilisation of the multiple layers of ilio-tibial tract from
      distal to proximal makes an excellent exposure of the PLC structures with absence
      of morbidity.

PMID- 16951980
TI  - Comparison of direct and indirect interference screw fixation for tendon graft in
      rabbits.
AB  - For ACL reconstruction, interference screw can fix the graft in the bone tunnel
      closer to the articular surface. However, direct interference screw fixation has
      a possibility to damage the tendon graft at the time of screw insertion, and the
      bone-tendon contact area is limited within the tunnel. To avoid the damage to the
      tendon graft at the time of screw insertion and to increase the bone-tendon
      contact area, a free bone plug was interposed between screw and tendon graft
      (indirect interference screw fixation). The purpose of this study was to compare
      ultimate load strength and histological findings between two techniques in a
      rabbit model. Ultimate pull-out load tests and histological examinations were
      evaluated at time 0, 3 and 6 weeks. The ultimate failure load of indirect
      interference screw fixation was significantly higher than that of direct
      interference screw fixation immediately after surgery (P < 0.05). Histologically,
      the interface tissues between tendon graft and host bone were more organized and
      matured in indirect technique. These findings showed that indirect interference
      screw fixation for tendon graft increased fixation strength at the graft-bone
      interface, providing quicker graft-bone healing.

PMID- 16951984
TI  - Genetic relatedness of six North-Indian butterfly species (Lepidoptera :Pieridae)
      based on 16S rRNA sequence analysis.
AB  - The present work involves the assessment of level of genetic relatedness or
      divergence amongst the six North-Indian species of Lepidoptera belonging to
      family Pieridae and sub family Pierinae on the basis of sequence variation of 16S
      ribosomal RNA. The PCR amplified products of these species were directly
      sequenced using ABI Prism BigDye Terminator Sequencing Kits (Applied Biosystems).
      The multiple nucleotide sequence alignment analysis has revealed several
      differences across these species. Significantly high percentage of A + T base
      composition content ranging between 73.13% (Ixias pyrene ) and 79.20 % (Pieris
      brassica) was observed in studied species. The percentage divergence in the
      investigated species of Pieridae family varied from 5.5% to 21.7%. The two
      species of Catopsilia revealed minimum sequence divergence of only 5.5%, whereas
      the other two groups of Ixias and Pieris revealed 15.5% and 8.6% sequence
      divergence, respectively. Pieris canidia and Ixias pyrene are genetically most
      divergent (21.7%) amongst the studied lepidopteran species. Phylogenetic analysis
      based on 16S rRNA nucleotide sequence revealed grouping of six species of
      Lepidoptera in the form of two different clusters, each cluster being represented
      by two species from the same genera. The separate taxonomic grouping of these
      Indian species has been observed when compared with several species of Piernae
      and Coliadinae subfamilies from other country isolates.

PMID- 16951986
TI  - Transforming growth factor-beta in cancer and metastasis.
AB  - Transforming growth factor-beta (TGF-beta) is a multifunctional regulatory
      polypeptide that is the prototypical member of a large family of cytokines that
      controls many aspects of cellular function, including cellular proliferation,
      differentiation, migration, apoptosis, adhesion, angiogenesis, immune
      surveillance, and survival. The actions of TGF-beta are dependent on several
      factors including cell type, growth conditions, and the presence of other
      polypeptide growth factors. One of the biological effects of TGF-beta is the
      inhibition of proliferation of most normal epithelial cells using an autocrine
      mechanism of action, and this suggests a tumor suppressor role for TGF-beta. Loss
      of autocrine TGF-beta activity and/or responsiveness to exogenous TGF-beta
      appears to provide some epithelial cells with a growth advantage leading to
      malignant progression. This suggests a pro-oncogenic role for TGF-beta in
      addition to its tumor suppressor role. During the early phase of epithelial
      tumorigenesis, TGF-beta inhibits primary tumor development and growth by inducing
      cell cycle arrest and apoptosis. In late stages of tumor progression when tumor
      cells become resistant to growth inhibition by TGF-beta due to inactivation of
      the TGF-beta signaling pathway or aberrant regulation of the cell cycle, the role
      of TGF-beta becomes one of tumor promotion. Resistance to TGF-beta-mediated
      inhibition of proliferation is frequently observed in multiple human cancers, as
      are various alterations in the complex TGF-beta signaling and cell cycle
      pathways. TGF-beta can exert effects on tumor and stromal cells as well as alter
      the responsiveness of tumor cells to TGF-beta to stimulate invasion,
      angiogenesis, and metastasis, and to inhibit immune surveillance. Because of the
      dual role of TGF-beta as a tumor suppressor and pro-oncogenic factor, members of
      the TGF-beta signaling pathway are being considered as predictive biomarkers for
      progressive tumorigenesis, as well as molecular targets for prevention and
      treatment of cancer and metastasis.

PMID- 16951987
TI  - TNF-alpha in promotion and progression of cancer.
AB  - Tumour necrosis factor alpha is a member of the TNF/TNFR cytokine superfamily. In
      common with other family members, TNF-alpha is involved in maintenance and
      homeostasis of the immune system, inflammation and host defence. However, there
      is a 'dark side' to this powerful cytokine; it is now clear that, especially in
      middle and old age, TNF-alpha is involved in pathological processes such as
      chronic inflammation, autoimmunity and, in apparent contradiction to its name,
      malignant disease. This article will discuss the involvement of TNF-alpha in the
      inflammatory network that contributes to all stages of the malignant process, and
      consider the possibility that TNF-alpha may be a target for cancer therapy.

PMID- 16951989
TI  - Sociodemographic risk factors for autism in a US metropolitan area.
AB  - The present study examined the association between autism and sociodemographic
      factors, overall and in subgroups of children with autism with and without mental
      retardation (Autism/MR and Autism/No MR, respectively); the association was
      further examined in subanalyses by child's source of ascertainment to assess the
      presence of ascertainment bias. In the main analyses, one marker of higher social
      class (higher median family income) was significantly associated with autism
      overall. Both markers of higher social class (higher maternal education and
      higher median family income) were significantly associated with autism/no MR, but
      not associated with autism/MR. In the subanalyses, associations with social class
      varied by ascertainment source. Future studies should consider phenotypic
      subgroups of children with autism and must consider potential ascertainment bias.

PMID- 16951990
TI  - The relationship between threat appraisal and social constraints in cancer
      survivors and their spouses.
AB  - : Social constraints stem from unsupportive social environments and are
      associated with reluctance to discuss stressor-related thoughts and feelings.
      Support deterioration and erosion models provide a framework for explaining how a
      cancer patient's threat appraisal contributes to a spouse's inadvertent
      constraint on the patient's emotional expression. Also, based on social
      comparison theory and the convoy model, a discrepancy in threat appraisal between
      patient and spouse may create social constraints. Contrary to social cognitive
      processing theories, we hypothesized that threat appraisals may be an antecedent
      of social constraints, rather than a consequence. Cancer patients (n=75) and
      their spouses (n=75) completed questionnaires assessing cancer-related threat
      appraisals and perceived spousal social constraints at two time points. Cross
      lagged panel design results suggested that patient appraisal precedes and
      predicts patients' perception of social constraints. However, patient and spouse
      appraisals did not significantly interact in predicting spousal constraints.
      Limitations and implications are discussed.

PMID- 16951991
TI  - Positive and negative religious coping in German breast cancer patients.
AB  - A growing interest has been focusing on the relationship between religious coping
      and psychosocial adjustment among cancer patients. However, previous research
      mostly has not differentiated between positive and negative components of
      religious coping. The current cross-sectional study investigated the role of both
      positive religious coping, i.e., a confident and constructive turning to
      religion, and negative religious coping, i.e., religious struggle and doubt, in a
      sample of 156 German breast cancer patients. Participants were assessed upon
      admission to an inpatient rehabilitation program. In addition to religious
      coping, two basic nonreligious coping styles (depressive coping and active
      problem-focused coping) and psychosocial adjustment (anxiety and depression) were
      measured. Major research questions concerning the mediating role of nonreligious
      coping and the relative predictive power of positive and negative religious
      coping were primarily addressed using structural equation modeling. Results
      indicated that the relationship between religious coping and psychosocial
      outcomes was completely mediated by nonreligious coping, whereby only depressive
      coping and not active problem-focused coping proved to be a mediating variable.
      Positive and negative religious coping were somewhat positively related to each
      other; their (indirect) predictive power on psychosocial adjustment was identical
      though in an opposite direction. All in all, the results correspond to previous
      Anglo-American research. There are, however, some discrepancies which may be due
      to the specific religious-cultural background in Germany.

PMID- 16951988
TI  - Molecular regulation of osteoclast activity.
AB  - Osteoclasts are multinucleated cells derived from hematopoietic precursors that
      are primarily responsible for the degradation of mineralized bone during bone
      development, homeostasis and repair. In various skeletal disorders such as
      osteoporosis, hypercalcemia of malignancy, tumor metastases and Paget's disease,
      bone resorption by osteoclasts exceeds bone formation by osteoblasts leading to
      decreased bone mass, skeletal fragility and bone fracture. The overall rate of
      osteoclastic bone resorption is regulated either at the level of differentiation
      of osteoclasts from their monocytic/macrophage precursor pool or through the
      regulation of key functional proteins whose specific activities in the mature
      osteoclast control its attachment, migration and resorption. Thus, reducing
      osteoclast numbers and/or decreasing the bone resorbing activity of osteoclasts
      are two common therapeutic approaches for the treatment of hyper-resorptive
      skeletal diseases. In this review, several of the key functional players involved
      in the regulation of osteoclast activity will be discussed.

PMID- 16951992
TI  - Effects of metal-binding properties of human Kv channel-interacting proteins on
      their molecular structure and binding with Kv4.2 channel.
AB  - The goal of the present study is to explore whether Ca2+ and Mg2+-binding
      properties of isomeric Kv channel-interacting proteins (KChIPs) have different
      effects on their molecular structure and the binding with Kv channel. 8
      Anilinonaphthalene- 1-sulfonate fluorescence measurement showed that KChIP4.1 and
      KChIP2.2 possessed one and two types of Ca2+-binding sites, respectively, and
      only one type of Mg2+-binding site was noted in the two KChIP proteins. Removal
      of EF-hand 4 (EF-4) caused a marked drop in their high affinities for Ca2+, but
      the binding affinity for Mg2+ remained mostly the same. Unlike KChIP4.1, the
      intact EF-4 was essential for the Kv channel-binding ability of KChIP2.2 in a
      metal-free buffer. Nevertheless, the interaction of wild-type KChIPs and EF-4
      truncated mutants with Kv channel was enhanced by the addition of Mg2+ and Ca2+.
      In contrast to KChIP4.1, the thermal stability of KChIP2.2 was decreased by the
      binding of Mg2+ and Ca2+. These results suggest that the conformational change
      with metal-bound KChIP4.1 is crucial for its interaction with Kv channel but not
      for KChIP2.2, and that the Mg2+- and Ca2+-binding properties of KChIP2.2 and
      KChIP4.1 have different effects on their molecular structure.

PMID- 16951993
TI  - Kinetics and mechanism for the reaction of cysteine with hydrogen peroxide in
      amorphous polyvinylpyrrolidone lyophiles.
AB  - PURPOSE: Peroxide impurities play a critical role in drug oxidation. In metal
      free aqueous solutions, hydrogen peroxide (H(2)O(2)) induced thiol oxidation
      involves a bimolecular nucleophilic reaction to form a reactive sulfenic acid
      intermediate (RSOH), which reacts with a second thiol to form a disulfide (RSSR).
      This study examines the reaction of cysteine (CSH) and H(2)O(2) in amorphous
      polyvinylpyrrolidone (PVP) lyophiles to explore the possible relevance of the
      solution mechanism to reactivity in an amorphous glass. MATERIALS AND METHODS:
      Amorphous PVP lyophiles containing CSH and H(2)O(2) at varying initial 'pH' and
      reactant concentrations were prepared by methods designed to minimize reaction
      during lyophilization. Kinetic studies were conducted anaerobically at 25 degrees
      C and reactants and products were monitored by HPLC. Products were characterized
      and the kinetic data were fit to models adapted from the solution mechanism.
      RESULTS: Key differences in the reactions in aqueous solution and amorphous PVP
      are: (1) while only cystine (CSSC) forms in solution, three degradants-cysteine
      sulfinic acid (CSO(2)H), cysteine sulfonic acid (CSO(3)H) and cystine (CSSC)-
      form in amorphous PVP; (2) simple bimolecular kinetics govern the solution
      reaction while initial rates in amorphous PVP suggested more complex kinetics
      (i.e., non-unity values for reaction order); and (3) heterogeneous (i.e.,
      biphasic) reaction dynamics are evident in amorphous PVP. The differences in
      product formation and apparent reaction orders in the solid-state could be
      rationalized by partitioning of the same reactive intermediate to multiple
      products in the solid-state due to the restricted mobility of CSH. Beyond the
      initial rate region, the kinetics in amorphous PVP could be described by the
      Kohlrausch-Williams-Watts (KWW) stretched-exponential equation or by assuming two
      populations of reactant molecules having different reactivities. CONCLUSIONS:
      When reactive intermediates are involved, differences in degradant profiles and
      other characteristics (e.g., rate constants, apparent reaction order) in the
      amorphous-state may simply reflect altered rates for individual reaction steps
      due to glass-induced changes in relative reactant mobilities rather than a change
      in overall mechanism.

PMID- 16951994
TI  - Lipid injectable emulsions: Pharmacopeial and safety issues.
AB  - Lipid injectable emulsions have been routinely used in patients worldwide for
      over 40 years as a nutritional supplement in patients requiring parenteral
      nutrition. They can be given as a separate infusion or added into total
      parenteral nutrition admixtures. Despite such broad use, no pharmacopeial
      standards exist with respect to the optimal pharmaceutical characteristics of the
      formulation. Several attempts to establish standard physical and chemical
      attributes have been attempted by various pharmacopeias around the world, but
      without success largely due to technical issues regarding the creation of globule
      size limits. Recently, the United States Pharmacopeia has revised its previous
      efforts and developed two methods and criteria (under Chapter <729>) to measure
      the mean droplet size (Method I), and the large-diameter tail > 5 mum (Method II)
      of the globule size distribution to verify the stability of lipid injectable
      emulsions. Importantly, it is the latter size limits of Method II that have the
      greatest implications for infusion safety. The major safety issues involving
      lipid injectable emulsions include impairments in plasma clearance in susceptible
      patients, and the infusion of an unstable emulsion containing large quantities of
      potentially embolic fat globules. Recent animal studies investigating the
      toxicity from the infusion of unstable lipid injectable emulsions have shown
      evidence of oxidative stress and tissue damage to the liver when recommended
      globule size limits determined by Method II of the USP are exceeded. Adoption of
      Chapter <729> of the USP seems appropriate at this time.

PMID- 16951995
TI  - Intra- and inter-ethnic differences in the allele frequencies of cytochrome P450
      2B6 gene in Chinese.
AB  - This study aimed to investigate the allele frequencies of CYP2B6 gene in 193 Han
      Chinese and compared with 91 Uygur Chinese. Five single nucleotide polymorphisms
      of CYP2B6, 64C > T, 516G > T, 777C > A, 785A > G and 1459C > T, were tested using
      the polymerase chain reaction-restriction fragment length polymorphism method.
      The allele frequencies for CYP2B6*2, CYP2B6*3, CYP2B6*4, CYP2B6*5, CYP2B6*6,
      CYP2B6*7 and CYP2B6*9 in Han and Uygur Chinese were 0.034 and 0.027, 0 and 0.011,
      0.091 and 0.033, 0.003 and 0.049, 0.184 and 0.214, 0 and 0.022, and 0.018 and
      0.044, respectively, with CYP2B6*4, CYP2B6*5, and CYP2B6*7 being significantly
      different between these two races (P < 0.05). CYP2B6*6 was the most prevalent
      allele among all detected variants in Han and Uygur Chinese. The most frequent
      genotypes were CYP2B6*1/CYP2B6*1 (50.8%), CYP2B6*1/CYP2B6*6 (24.4%), and
      CYP2B6*1/CYP2B6*4 (7.3%) in Han subjects, whereas the most frequent genotypes in
      Uygur subjects were CYP2B6*1/CYP2B6*1 (36.3%), CYP2B6*1/CYP2B6*6 (25.3%),
      CYP2B6*1/CYP2B6*5 (5.5%) and CYP2B6*6/CYP2B6*6 (5.5%). The frequencies of 64C > T
      mutation in Han and Uygur Chinese were significantly lower than that in American
      Caucasian (P < 0.05). These results indicate that there were marked ethnic
      differences in the mutant frequencies of CYP2B6 between Chinese and other ethnic
      groups. Further studies are warranted to explore the clinical impact of such
      ethnic differences.

PMID- 16951997
TI  - Population pharmacokinetic/pharmacodynamic modelling of the analgesic effects of
      tramadol in pediatrics.
AB  - BACKGROUND AND PURPOSE: The efficacy of tramadol (T) in children is not clearly
      understood because it is still unknown the ability of that population to form the
      active metabolite O-demethyltramadol (M1) and, whether or not the parent compound
      has a contribution to the efficacy. The aim was to develop a population
      pharmacokinetic/pharmacodynamic model for T in pediatrics, identifying the main
      active components. MATERIALS AND METHODS: One hundred four children, mean age
      (4.55 years) received intravenously 1 mg/kg dose of T over 2.5 min at the end of
      surgery. If pain relief was inadequate, then an additional 0.33 mg/kg dose was
      given at 15, 30 and/or 45 min. Plasma samples and analgesic responses such as
      crying and movement were measured during a 6-h period. RESULTS: The estimates of
      the apparent volumes of distribution of the central compartment and at steady
      state and total plasma clearance of T were 8 l, 46.2 l, and 15.2 l/h,
      respectively. M1 formation clearance represented only a minor elimination pathway
      of T. Effect site concentrations of T and M1 were found to be the best predictors
      of the movement and crying responses, respectively. Steady-state plasma
      concentration levels of T and M1 of 100 and 15 ng/ml were associated with a 95%
      probability of adequate pain relief. CONCLUSIONS: Children have the ability to
      produce enough M1 to achieve proper pain relief. The response variables
      investigated give further evidence that not only the opioid effects of the
      metabolite are relevant, also the non-opiod effects of tramadol seem to give a
      significant contribution in its clinical use.

PMID- 16951996
TI  - Metabolic and efflux properties of Caco-2 cells stably transfected with nuclear
      receptors.
AB  - PURPOSE: To characterise in detail the patterns of expression and functional
      activities of CYP and efflux pump genes in Caco-2 cells stably transfected with
      human Pregnane X Receptor or murine Constitutive Androstane Receptor. MATERIALS
      AND METHODS: Cell lines transfected with nuclear receptors were treated with
      established ligands, and gene expression of CYP and efflux pump genes were
      quantified by qRT-PCR and Western blot. P-glycoprotein activity was assessed by
      measuring calcein-AM accumulation and bidirectional permeability coefficients of
      digoxin and quinidine. CYP activities were measured with both fluorescent and non
      fluorescent substrates. RESULTS: hPXR and mCAR upregulated some CYP and efflux
      pump genes ligand dependently. P-glycoprotein level was increased, but CYP3A4
      protein remained below the limit of detection. P-glycoprotein activity was
      markedly elevated in Caco/mCAR cells and more modestly in Caco/hPXR cells. CYP3A4
      activity remained lower than that in vitamin D-treated Caco-2 cells. CONCLUSIONS:
      Nuclear receptors can modulate the expression of metabolic genes in Caco-2 cells,
      but the overall level of metabolism could not be efficiently controlled. P
      glycoprotein activity increased, but CYP activities remained very low.

PMID- 16951998
TI  - Predicting plutonium decorporation efficacy after intravenous administration of
      DTPA formulations: Study of pharmacokinetic-pharmacodynamic relationships in
      rats.
AB  - PURPOSE: The objectives of this study were: 1) to assess the relationship between
      plutonium decorporation (increased excretion and reduced retention in main organs
      of deposition) induced by intravenous liposome formulations of the chelating
      agent diethylene triamine pentaacetic acid (DTPA) and its pharmacokinetics, and
      2) to model the renal excretion of plutonium after treatment with liposome
      encapsulated DTPA in order to predict its efficacy and to optimise treatment
      schedules. MATERIALS AND METHODS: Pharmacokinetic parameters from plasma or
      urinary data (days 0-16 sample collections) were modelled versus decorporation
      efficacy, and best correlations were selected for their goodness of fit. RESULTS:
      The plutonium decorporation enhancement by DTPA liposomal formulations was well
      described by logistic models and the best correlation was observed with the area
      under the DTPA concentration curve of each formulation. The plutonium urinary
      excretion rates decreased mono-exponentially as a function of time after a single
      dose and the proposed model allowed a simple determination of the elimination
      half-life of the Pu-DTPA complex, a reasonably good approximation of the long
      term efficacy of the treatments from truncated urinary data. CONCLUSIONS: Both
      liposomal formulations of chelating agents and pharmacokinetic approaches to
      plutonium decorporation should be helpful in optimising treatment protocols.

PMID- 16951999
TI  - The absorption of darbepoetin alfa occurs predominantly via the lymphatics
      following subcutaneous administration to sheep.
AB  - PURPOSE: To determine the contribution of the lymphatics to the systemic
      availability of darbepoetin alfa (DA) using an established sheep model. MATERIALS
      AND METHODS: DA was administered either by intravenous (IV) injection (0.2, 0.5
      or 2 microg/kg) or by subcutaneous (SC) administration (2 microg/kg) into the
      interdigital space of the hind leg. A SC control group was used to determine the
      absolute bioavailability (F (sys)). Cannulation of the peripheral lymphatics in a
      parallel SC group allowed the continuous collection of lymph draining the
      injection site and determination of the cumulative amount of DA absorbed via the
      lymphatics. Serum and lymph concentrations of DA were determined by ELISA. The
      fraction of the dose absorbed into the lymphatics (F (lymph)) relative to the
      fraction absorbed directly into the blood (F (blood)) was determined using a
      compartmental approach. RESULTS: Dose-linear pharmacokinetics was observed within
      the dose range investigated. The bioavailability was virtually complete following
      SC injection into the interdigital space (88.4 +/- 15.7%). A high proportion of
      the administered dose was recovered in peripheral lymph (90.2 +/- 4.4%) resulting
      in a substantial reduction in the systemic availability in lymph cannulated
      animals (3.7%). CONCLUSION: The high recovery of DA in the peripheral lymph
      demonstrated near complete absorption of this recombinant protein via the
      lymphatics in a lymph cannulated sheep model.

PMID- 16952000
TI  - Alterations in neuronal transport but not blood-brain barrier transport are
      observed during gamma-hydroxybutyrate (GHB) sedative/hypnotic tolerance.
AB  - PURPOSE: To investigate if gamma-Hydroxybutyrate (GHB) tolerance is mediated by
      alterations in GHB systemic pharmacokinetics, transport (blood brain barrier
      (BBB) and neuronal) or membrane fluidity. MATERIALS AND METHODS: GHB tolerance in
      rats was attained by repeated GHB administration (5.31 mmol/kg, s.c., QD for 5
      days). GHB sedative/hypnotic effects were measured daily. GHB pharmacokinetics
      were determined on day 5. In separate groups, on day 6, in situ brain perfusion
      was performed to assess BBB transport alterations; or in vitro studies were
      performed (fluorescence polarization measurements of neuronal membrane fluidity
      or [3H]GABA neuronal accumulation). RESULTS: GHB sedative/hypnotic tolerance was
      observed by day 5. No significant GHB pharmacokinetic or BBB transport
      differences were observed between treated and control rats. Neuronal membrane
      preparations from GHB tolerant rats showed a significant decrease in fluorescence
      polarization (treated-0.320 +/- 0.009, n = 5; control-0.299 +/- 0.009, n = 5; p <
      0.05). [3H]GABA neuronal transport Vmax was significantly increased in tolerant
      rats (2,110.66 +/- 91.06 pmol/mg protein/min vs control (1,612.68 +/- 176.03
      pmol/mg protein/min; n = 7 p < 0.05). CONCLUSIONS: Short term GHB administration
      at moderate doses results in the development of tolerance which is not due to
      altered systemic pharmacokinetics or altered BBB transport, but might be due to
      enhanced membrane rigidity and increased GABA reuptake.

PMID- 16952001
TI  - Porcine alveolar epithelial cells in primary culture: morphological,
      bioelectrical and immunocytochemical characterization.
AB  - PURPOSE: The purpose of this study was to establish a primary culture of porcine
      lung epithelial cells as an alternative to the currently existing cell cultures
      from other species, such as e.g., rat or human. Primary porcine lung epithelial
      cells were isolated, cultivated and analyzed at distinct time points after
      isolation. MATERIALS AND METHODS: The main part of the work focused on the
      morphology of the cells and the detection of alveolar epithelial cell markers by
      using electron microscopy, immunofluorescence microscopy and immunoblotting.
      Regarding a later use for in vitro pulmonary drug absorption studies the barrier
      properties of the cell monolayer were evaluated by monitoring bioelectrical
      parameters and by marker transport. RESULTS: Epithelial cells isolated from
      porcine lung grew to confluent monolayers with typical intercellular junctions
      within a few days. Maximum transepithelial resistance of about 2,000 Omega cm2
      was achieved and demonstrated the formation of a tight epithelial barrier.
      Permeability data of sodium fluorescein recommended a minimal transepithelial
      resistance of 600 Omega cm2 for transport studies. The cell population changed
      from a heterogeneous morphology and marker distribution (caveolin-1, pro-SP-C,
      surface sugars) towards a monolayer consisting of two cell types resembling type
      I and type II pneumocytes. CONCLUSIONS: The porcine alveolar epithelial primary
      cell culture holds promise for drug transport studies, because it shares major
      hallmarks of the mammalian alveolar epithelium and it is easily available and
      scaled up for drug screening.

PMID- 16952002
TI  - Increased transport of resveratrol across monolayers of the human intestinal Caco
      2 cells is mediated by inhibition and saturation of metabolites.
AB  - PURPOSE: The study's aim was to investigate the dose-dependent effect of
      sulfation and glucuronidation on intestinal absorption of resveratrol, a dietary
      constituent found in grapes and various medical plants. MATERIALS AND METHODS:
      The intestinal epithelial membrane transport kinetics and metabolism of
      resveratrol (10-200 microM) was studied using Caco-2 monolayers cultured in
      Transwells. RESULTS: Along with resveratrol it was possible to identify three
      metabolites, namely, resveratrol-4'-O-glucuronide (M1), resveratrol 3-O
      gucuronide (M2), and resveratrol-3-O-sulfate (M3) by LC/MS and NMR. Efflux of the
      glucuronides M1 and M2 followed Michaelis-Menten kinetics significantly favouring
      basolateral efflux. The predominant metabolite was the monosulfate M3, however,
      its formation was strongly inhibited at higher resveratrol concentrations. As
      biotransformation was either inhibited or saturated, total amount of resveratrol
      transported across the Caco-2 monolayers increased as much as 3.5-fold at 200
      microM resveratrol. This value might be even higher when taking into account the
      high intracellular concentration of resveratrol, which accounted for up to 61% of
      the applied dose. CONCLUSIONS: Our data demonstrate a concentration-dependent
      biotransformation of resveratrol in Caco-2 cells, which may also apply to human
      enterocytes affecting oral bioavailability.

PMID- 16952003
TI  - Improving the oral efficacy of recombinant granulocyte colony-stimulating factor
      and transferrin fusion protein by spacer optimization.
AB  - PURPOSE: To improve the oral efficacy of the recombinant fusion protein
      containing granulocyte colony-stimulating factor (G-CSF) and transferrin (Tf) by
      inserting a linker between the two protein domains. MATERIALS AND METHODS:
      Oligonucleotides encoding flexible and helix-forming peptides were inserted to
      the recombinant plasmids. The fusion protein without linker insertion was used
      for comparison. The G-CSF cell-proliferation and Tf receptor-binding activities
      of the fusion proteins were tested in NFS-60 cells and Caco-2 cells,
      respectively, and in vivo myelopoietic assay with both subcutaneous and oral
      administration was performed in BDF1 mice. RESULTS: All fusion proteins produced
      from transfected HEK293 cells were positive in Western-blotting assay with anti-G
      CSF and anti-Tf antibodies. Among them, the fusion protein with a long helical
      (H4-2) linker showed the highest activity in NFS-60 cell proliferation assay,
      with an EC50 about ten-fold lower than that of the non-linker fusion protein. The
      fusion protein with H4-2 linker also showed a significantly higher myelopoietic
      effect when administered either subcutaneously or orally in BDF1 mice.
      CONCLUSION: The insertion of a linker peptide, such as the helix linker H4-2,
      between G-CSF and Tf domains in the recombinant fusion protein can improve
      significantly both in vitro and in vivo myelopoietic activity over the non-linker
      fusion protein.

PMID- 16952004
TI  - Molecular properties of flurbiprofen and its solid dispersions with Eudragit
      RL100 studied by high- and low-resolution solid-state nuclear magnetic resonance.
AB  - PURPOSE: Investigation of the conformational and molecular dynamic properties of
      the acidic and sodium salt forms of Flurbiprofen and their solid dispersions with
      Eudragit RL100, obtained by two different preparation methods (physical mixtures
      and coevaporates), and of the mixing degree between the two components in the
      dispersions. MATERIALS AND METHODS: 1H and 13C high-resolution solid state NMR
      techniques, including Single Pulse Excitation-MAS, CP-MAS, FSLG-HETCOR; low
      resolution 1H FID analysis; 1H spin-lattice relaxation time measurements.
      RESULTS: Conformational, molecular packing and dynamic differences were observed
      between the two pure forms of flurbiprofen, as well as between the pure drugs and
      the corresponding coevaporates. In the coevaporates of the two flurbiprofen
      forms, drug and polymer appear intimately mixed; their chemical interactions were
      detected and characterized. CONCLUSIONS: A combined analysis of several 13C and
      1H high- and low-resolution solid state NMR experiments allowed the investigation
      of the conformational and dynamic properties of the pure drugs and of the solid
      dispersions with the polymer, as well as of the degree of mixing between drug and
      polymer and of the chemical nature of their interaction. Such information could
      be compared to the in vitro drug release profiles given by these solid
      dispersions.

PMID- 16952005
TI  - Chemical analysis of solid-state irradiated human insulin.
AB  - PURPOSE: To study the chemical modifications induced upon irradiation of solid
      human insulin at radiosterilization doses and investigate the influence of the
      absorbed dose on radiolysis. MATERIALS AND METHODS: Volatile radiolytic products
      were monitored by gas chromatography coupled with mass spectrometry (GC-MS) and
      non-volatile products by two different high performance liquid chromatography
      (HPLC) methods: the formation of higher molecular weight proteins was assessed by
      size exclusion liquid chromatography whereas assays for related compounds and
      chemical potency tests were carried out using reverse-phase HPLC-UV.
      Conformational changes were investigated by measurements of circular dichroism.
      RESULTS: After gamma irradiation at 10 kGy, the recovery of insulin was 96.8%;
      higher molecular weight proteins accounted for 0.35% (relative peak area) and
      other related compounds (including A21 desamido insulin) represented 1.29%. No
      major structural changes and no volatile radiolytic compounds were detected.
      CONCLUSION: Human insulin samples irradiated in the solid-state at 10 kGy (gamma
      rays) and 14 kGy (electron-beam) meet the European Pharmacopoeia requirements and
      can be considered as quite stable towards radiation from a chemical analysis
      viewpoint.

PMID- 16952006
TI  - Comparative relaxation dynamics of glucose and maltitol.
AB  - PURPOSE: To demonstrate the utility of differential scanning calorimetry (DSC)
      for determining activation energy landscape in amorphous pharmaceutical systems
      throughout the sub-Tg and Tg regions. MATERIALS AND METHODS: DSC was employed to
      determine the effective activation energies (E) of the relaxation in sub-Tg and
      Tg regions as well as the sizes of cooperatively rearranging regions in glassy
      maltitol and glucose. RESULTS: It has been found that in the sub-Tg region E
      decreases with decreasing T reaching the values approximately 60 (glucose) and
      approximately 70 (maltitol) kJ mol(-1) that are comparable to the literature
      values of the activation energies for the beta-relaxation. In the Tg region E
      decreases (from approximately 250 to approximately 150 kJ mol(-1) in maltitol and
      from approximately 220 to approximately 170 kJ mol(-1) in glucose) with
      increasing T as typically found for the alpha-relaxation. From the heat capacity
      measurements the sizes of cooperatively rearranging regions have been determined
      as 3.1 (maltitol) and 3.3 (glucose) nm. CONCLUSIONS: DSC can be used for
      evaluating the energy landscapes. The E values for maltitol are somewhat greater
      than for glucose due to the added impeding effect of the bulky substitute group
      in maltitol. The comparable sizes of the cooperatively rearranging regions
      suggest a similarity of the heterogeneous glassy structures of the two compounds.

PMID- 16952007
TI  - Non-competitive inhibitory activities of morphinan and morphine derivatives at
      the alpha 3 beta 4 Neuronal nicotinic acetylcholine receptor determined using
      nonlinear chromatography and chemometric techniques.
AB  - PURPOSE: A series of morphine and morphinan derivatives were chromatographed on a
      column containing immobilized cellular membranes from a cell line expressing the
      alpha 3 beta 4 neuronal nicotinic acetylcholine receptor (alpha 3 beta 4 nAChR).
      METHODS: The results were analyzed using chemometric and molecular modeling
      techniques in order to predict the noncompetitive inhibitory (NCI) activity of
      these compounds, the molecular basis for the predicted activity and the binding
      sites of the inhibitors. RESULTS: The data demonstrated that seven of seven
      morphinans were NCIs and bound in the central lumen of the nAChR while only 2 of
      13 morphine derivatives had NCI activity and these compounds most likely bound at
      the quinacrine binding site on the nAChR. The predicted activities were confirmed
      using functional inhibition studies. CONCLUSIONS: The results indicate that this
      approach can be used to rapidly assess pharmacological activity and to guide new
      drug design.

PMID- 16952008
TI  - Development of a novel method for the preparation of thiolated polyacrylic acid
      nanoparticles.
AB  - PURPOSE: To develop a novel method for the preparation of thiolated polyacrylic
      acid nanoparticles via ionic gelation. MATERIALS AND METHODS: In a first step
      nanoparticles were generated by ionotropic gelation of polyacrylic acid (PAA) of
      three different molecular weights (100, 240 and 450 kDa) and various cations
      including Ca2+, Mg2+, Zn2+, Al3+ and Fe3+. Via in vitro characterization of the
      particles (particle size, size distribution and zeta potential) the optimal
      preparation conditions were established. Taking into consideration, that
      thiolated polyacrylic acid (PAA-Cys) displays higher mucoadhesive and permeation
      enhancing properties than unmodified PAA, PAA-Cys nanoparticles were produced in
      the same manner with Ca2+, as the most promising results concerning particle size
      and stability of particles could be achieved with this ionic crosslinker. The
      nanoparticles were stabilized via the formation of inter- and intrachain
      disulfide bonds within these particles due to oxidation with H2O2. Ca2+ was
      removed proximately by the addition of EDTA and exhaustive dialysis. RESULTS:
      Using the preparation method described above PAA-Cys nanoparticles of a mean
      diameter of about 220 nm (PAA(100)-Cys), 250 nm (PAA(240)-Cys) and 295 nm
      (PAA(450)-Cys) can be generated. In comparison to PAA nanoparticles ionically
      crosslinked with Ca2+, the removal of the crosslinker Ca2+ from PAA-Cys particles
      led to a nearly three-fold decrease in the zeta potential, from about -7 up to 
      20 mV. Apart from this advantage, covalently crosslinked PAA-Cys nanoparticles
      were more firm as they remained stable when incubated in hydrochloride solution,
      whereas ionically crosslinked particles dissolved at pH lower than 5.
      CONCLUSIONS: This novel nanoparticulate delivery system seems to be a promising
      vehicle for the administration of therapeutic proteins, genes and antigens via
      mucosal membranes.

PMID- 16952009
TI  - Pegylated nanocapsules produced by an organic solvent-free method: Evaluation of
      their stealth properties.
AB  - PURPOSE: To develop from an original process, a novel generation of stealth
      lipidic nanocapsules in order to improve the lipophilic drug delivery in
      accessible sites. MATERIALS AND METHODS: Nanocapsules covered by PEG1500 stearate
      were obtained by a low energy emulsification method. Conductivity measurements
      and ternary diagram were performed to describe the formulation mechanism.
      Hemolytic dosage CH50 and pharmacokinetic study in rats have been achieved in
      order to study the stealth properties of nanocapsules. RESULTS: Transition from
      an O/W emulsion to a w/O/W emulsion was necessary to produce PEG1500 stearate
      nanocapsules. Interestingly nanocapsules with a size around 26 nm and a
      polydispersity index inferior to 0.1 were obtained. The CH50 test has revealed a
      very weak complement consumption in the presence of such nanocapsules. Moreover,
      after intravenous injection into rats, PEG1500 stearate nanocapsules exhibited
      long circulating properties. The experimental data support the concept of steric
      repulsion of the surface towards proteins, displayed by nanocapsules covered with
      PEG1500 stearate. These in vivo results were in agreement with the PEG1500
      density calculated at the nanocarrier surface. CONCLUSIONS: Injectable drug
      carriers have been developed. Their long-circulating properties could confer them
      a strong potential for lipophilic drug targeting.

PMID- 16952010
TI  - Effect of palifermin in a murine model of graft-versus-host disease (GVHD)
      associated with Th2 cytokine production, autoantibody production, and
      glomerulonephritis.
AB  - Palifermin (recombinant human keratinocyte growth factor) prevents the
      development of acute, lethal graft-versus-host disease (GVHD). It does so, at
      least in part, by protecting cells from injury. Another property of Palifermin is
      immune regulation. How the latter influences the evolution of GVHD remains
      uncertain. We explored the effect of Palifermin on GVHD in the DBA/2 -->
      ((DBA/2)x(C57BL/6))F(1)-hybrid strain combination, a model associated with
      autoantibody production and glomerulonephritis. Untreated recipients survived
      until at least day 150 post-induction. Palifermin-treated recipients succumbed
      between days 50 and 90 with levels of proteinuria of up to 20 g/L, ascites, and
      rapidly progressive, crescentic glomerulonephritis that was most severe in mice
      with the greatest levels of proteinuria. Kidney sections from both Palifermin
      treated and untreated recipients showed the presence of granular deposits of IgG,
      IgM, IgA, and C3 in the mesangium and the glomerular basement membrane. Electron
      microscopy confirmed the extensive glomerular immune complex deposition.
      Antinuclear and anti-dsDNA antibodies were present in sera from both treated and
      untreated recipients; however, those in the latter were only detectable if the
      serum was kept at 37 degrees C, indicating that they were cryoglobulins. IL-4 was
      detectable only in cultures from Palifermin-treated recipients and the levels of
      IL-5 and IL-13 were significantly higher in the Palifermin-treated group than in
      untreated GVHD mice. IFN-gamma was only detectable in untreated GVHD mice. These
      data suggest that although Palifermin can protect mice with acute GVHD, it
      exacerbates GVHD in a model associated with autoantibody production and a
      preponderance of Th2 cytokines.

PMID- 16952011
TI  - Microwave-triggered metal-enhanced chemiluminescence (MT-MEC): application to
      ultra-fast and ultra-sensitive clinical assays.
AB  - In this rapid communication we describe a new approach to protein detection with
      chemiluminescence. By combining common practices in protein detection with
      chemiluminescence, microwave technology, and metal-enhanced chemiluminescence, we
      show that we can use low power microwaves to substantially increase enzymatic
      chemiluminescent reaction rates on metal substrates. As a result, we have found
      that we can in essence trigger chemiluminescence with low power microwave (Mw)
      pulses and ultimately, perform on-demand protein detection assays. Using
      microwave triggered metal-enhanced chemiluminescence (MT-MEC), we not only
      improve the sensitivity of immunoassays with enhanced signal-to-noise ratios, but
      we also show that we can accurately quantify protein concentrations by
      integrating the photon flux for discrete time intervals.

PMID- 16952012
TI  - Simultaneous determination of acetylsalicylic acid and caffeine in pharmaceutical
      formulation by first derivative synchronous fluorimetric method.
AB  - A sensitive, rapid, and specific assay has been developed for the simultaneous
      determination of acetylsalicylic acid and caffeine in commercial tablets based on
      their natural fluorescence. The mixture of these drugs was resolved by first
      derivative synchronous fluorimetric technique using two scans. At Deltalambda=106
      nm, using first derivative synchronous scanning, only acetylsalicylic acid yields
      a detectable signal at 316 nm (peak to zero method) which is unaffected by
      caffeine. At Deltalambda=30 nm, the signal of caffeine at 288 nm (peak to zero
      method) is not affected by acetylsalicylic acid. The range of application is
      between 0.021 and 41.62 microg ml(-1) (correlation coefficient, R=0.9995) for
      acetylsalicylic acid and between 0.4486 and 44.86 microg ml(-1) (correlation
      coefficient, R=0.99786) for caffeine. The recovery range of 98.40-102% for
      acetylsalicylic acid and 90-100.5% for caffeine from their synthetic mixture was
      reported. Overall recovery of both compounds about 97-99% for acetylsalicylic
      acid and 97-98% for caffeine was obtained from real sample analysis. The
      detection limits are 0.0013 microg ml(-1) and 0.0306 microg ml(-1) for
      acetylsalicylic acid and caffeine, respectively. The relative standard deviation
      (n=10) for 20 microg ml(-1) of acetylsalicylic acid is 2.75% and for 2.2 microg
      ml(-1)of caffeine is 1.7%.

PMID- 16952013
TI  - Transgene constructs in coho salmon (Oncorhynchus kisutch) are repeated in a head
      to-tail fashion and can be integrated adjacent to horizontally-transmitted
      parasite DNA.
AB  - Currently, little information is available regarding the molecular organization
      of integrated transgenes in genetically-engineered fish. We performed a detailed
      structural analysis of an inserted transgene in one strain (M77) of transgenic
      coho salmon (Oncorhynchus kisutch) containing a salmon growth hormone gene
      construct (OnMTGH1). Microinjected DNA was found to have inserted into a single
      site in the coho salmon genome, and was organized with four complete internal
      copies and two partial terminal copies of the OnMTGH1 construct. All construct
      copies were organized in a direct-tandem (head-to-tail) repeat fashion in strain
      M77 and five additional strains (one also possessed a second recombinant junction
      fragment). For strain M77, the junctions between the transgene insert and the
      insertion point within the wild-type genome were cloned from strain-specific
      cosmid libraries and sequenced, revealing that the transgene insertion was
      accompanied by a deletion of 587 bp of wild-type DNA as well as a small insertion
      (19 bp) of unknown DNA upstream and a 14 bp direct- tandem duplication of
      sequence downstream. Upstream and downstream wild-type DNA sequence contained
      several repetitive sequence elements based on Southern blot analysis and homology
      to repetitive sequences in GenBank. In the downstream flank, a pseudogene
      sequence was also identified which has high homology to the CA membrane protein
      gene from Schistosoma japonicum, a parasite closely related to Sanguinicola sp.
      parasites which infect salmonids. Whether the presence of an inserted transgene
      and the presence of potentially horizontally-transmitted DNA are indicative of a
      genomic region with a predisposition for insertion of foreign DNA requires
      further study. The information derived from this transgene structure provides
      information useful for comparison to other transgenic organisms and for
      determination of the mechanism of transgene integration in lower vertebrates.

PMID- 16952014
TI  - Transgenic mice expressing PAX3-FKHR have multiple defects in muscle development,
      including ectopic skeletal myogenesis in the developing neural tube.
AB  - The t(2;13) chromosomal translocation is found in the majority of human alveolar
      rhabdomyosarcomas (RMS). The resulting PAX3-FKHR fusion protein contains PAX3 DNA
      binding domains fused to the potent transactivation domain of FKHR, suggesting
      that PAX3-FKHR functions to deregulate PAX3-specific target genes and signaling
      pathways. We previously developed transgenic mice expressing PAX3-FKHR under the
      control of mouse Pax3 regulatory sequences to test this hypothesis. We reported
      that PAX3-FKHR interferes with normal Pax3 developmental functions, with mice
      exhibiting neural tube and neural crest abnormalities that mimic those found in
      Pax3-deficient Splotch mice. Here we expanded those studies to show that
      developmental expression of PAX3-FKHR results in aberrant myogenesis in the
      developing somites and neural tube, leading to ectopic skeletal muscle formation
      in the mature spinal cord. Gene expression profiling indicated that PAX3-FKHR
      expression in the developing neural tube induces a myogenic pattern of gene
      expression at the expense of the normal neurogenic program. Somite defects in
      PAX3-FKHR transgenic animals resulted in skeletal malformations that included rib
      fusions and mis-attachments. As opposed to the neural tube defects, the severity
      of the rib phenotype was rescued by reducing Pax3 levels through mating with
      Splotch mice. Embryos from the transgenic line expressing the highest levels of
      PAX3-FKHR had severe neural tube defects, including exencephaly, and almost half
      of the embryos died between gestational ages E13.5-E15.5. Nearly all of the
      embryos that survived to term died after birth due to severe spina bifida, rather
      than the absence of a muscular diaphragm. These studies reveal a prominent role
      for PAX3-FKHR in disrupting Pax3 functions and in deregulating skeletal muscle
      development, suggesting that this fusion protein plays a critical role in the
      pathogenesis of alveolar RMS by influencing the commitment and differentiation of
      the myogenic cell lineage.

PMID- 16952015
TI  - Overexpression of Nd1, a novel Kelch family protein, in the heart of transgenic
      mice protects against doxorubicin-induced cardiomyopathy.
AB  - Doxorubicin is one of the most effective drugs available for cancer chemotherapy.
      However, the clinical use of doxorubicin has been greatly limited because of
      severe side effects on cardiomyocytes. Since Nd1-L, a novel actin-binding
      protein, is expressed most abundantly in the heart of adult mice, we examined a
      role of Nd1-L in doxorubicin-induced cardiomyopathy. When doxorubicin (5 mg/kg x
      4 times) was injected into adult mice at a 3-day-interval, approximately 50% of
      injected mice died within 4 weeks of the first injection. Nd1-L mRNA expression
      in the heart decreased within 3 weeks after the first injection and many
      cardiomyocytes of injected mice died by apoptosis. Overexpression of Nd1-L in the
      heart of transgenic mice protected the cardiomyocytes from apoptosis and improved
      survival rate after doxorubicin injection. Furthermore, activation of Erk1/2 was
      observed in cultured cells overexpressing Nd1-L. Thus, Nd1-L plays a critical
      role in protecting the heart from doxorubicin-induced cardiomyopathy.

PMID- 16952016
TI  - Transformation of poplar (Populus alba) plastids and expression of foreign
      proteins in tree chloroplasts.
AB  - Plastid transformation offers several unique advantages compared with nuclear
      genome transformation, such as high level of transgene expression within
      plastids, expressing multiple transgenes as operons, lack of position effect due
      to site-specific transgene integration, and reducing risks of gene flow via
      pollen due to maternal inheritance of the plastid genome. Plastid transformation
      has been applied to several herbal species, but as yet there are no applications
      to tree species. We report here the first successful plastid transformation in a
      tree species, Populus alba. A vector for plastid transformation of poplar
      (Populus alba) was constructed, which carried the spectinomycin resistance gene
      and the green fluorescence protein gene as marker genes. In the regenerated
      shoots, the site-specific integration of foreign genes and the establishment of a
      high homoplastomic state were confirmed. Immunoblot analysis and histological
      observations corroborated the accumulation of green fluorescence protein in
      chloroplasts. The establishment of a plastid transformation system in poplar
      provides a novel tool for tree biotechnology.

PMID- 16952017
TI  - Selective expression of an aP2/Fatty Acid Binding Protein 4-Cre transgene in non
      adipogenic tissues during embryonic development.
AB  - Mouse strains expressing the site-specific Cre recombinase facilitate conditional
      ablation or activation of genomic sequences when one or several exons of a gene
      of interest are flanked by loxP sites. Recently, several strains targeting Cre
      expression to adipocytes have been developed using promoter sequences from the
      aP2 (Fatty Acid Binding Protein 4, FABP4) gene for adipose tissue-specific gene
      expression studies. aP2/FABP4 is predominantly expressed in adipose tissue, and
      while this promoter provides adipocyte-restricted expression postnatally, its
      expression throughout embryonic development had not been previously
      characterized. In this report, we demonstrate that the aP2-Cre transgene is
      expressed and consistently localized within the embryo from mid-gestation stage
      9.5 dpc. By 15.5 dpc, beta-gal activity was detected primarily in the brown
      adipose tissue, trigeminal ganglia, dorsal root ganglia, cartilage primordia and
      vertebrae. Immunofluorescence staining for Cre recombinase and FABP4 protein
      showed a corresponding staining pattern similar to that of beta-gal, confirming
      that Cre recombinase was produced in the transgenic line at late stages of
      development, and overlapped with endogenous aP2/FABP4 production. Further, fat
      specific oil red O staining of tissue sections validated the presence of lipids
      in the stained tissues indicating that adipocytes and/or adipocyte-like cells
      were indeed present in these tissues. This is the first report to our knowledge
      to describe and confirm aP2/FABP4 promoter expression in this transgenic line
      during development in the mouse embryo and indicates that aP2/FABP4 expression
      occurs not only in mature adipocytes, but has a wider embryonic expression
      pattern than previously appreciated.

PMID- 16952018
TI  - An analytical model of gene evolution with 9 mutation parameters: an application
      to the amino acids coded by the common circular code.
AB  - We develop here an analytical evolutionary model based on a trinucleotide
      mutation matrix 64 x 64 with nine substitution parameters associated with the
      three types of substitutions in the three trinucleotide sites. It generalizes the
      previous models based on the nucleotide mutation matrices 4 x 4 and the
      trinucleotide mutation matrix 64 x 64 with three and six parameters. It
      determines at some time t the exact occurrence probabilities of trinucleotides
      mutating randomly according to these nine substitution parameters. An application
      of this model allows an evolutionary study of the common circular code [Formula:
      see text] of eukaryotes and prokaryotes and its 12 coded amino acids. The main
      property of this code [Formula: see text] is the retrieval of the reading frames
      in genes, both locally, i.e. anywhere in genes and in particular without a start
      codon, and automatically with a window of a few nucleotides. However, since its
      identification in 1996, amino acid information coded by [Formula: see text] has
      never been studied. Very unexpectedly, this evolutionary model demonstrates that
      random substitutions in this code [Formula: see text] and with particular values
      for the nine substitutions parameters retrieve after a certain time of evolution
      a frequency distribution of these 12 amino acids very close to the one coded by
      the actual genes.

PMID- 16952019
TI  - Threshold conditions for a non-autonomous epidemic system describing the
      population dynamics of dengue.
AB  - A non-autonomous dynamical system, in which the seasonal variation of a mosquito
      vector population is modeled, is proposed to investigate dengue overwintering. A
      time-dependent threshold, R(t), is deduced such that when its yearly average,
      denoted by R, is less than 1, the disease does not invade the populations and
      when R is greater than 1 it does. By not invading the population we mean that the
      number of infected individuals always decrease in subsequent seasons of
      transmission. Using the same threshold, all the qualitative features of the
      resulting epidemic can be understood. Our model suggests that trans-ovarial
      infection in the mosquitoes facilitates dengue overwintering. We also explain the
      delay between the peak in the mosquitoes population and the peak in dengue cases.

PMID- 16952020
TI  - Multidetector spiral CT renal angiography in the diagnosis of giant renal artery
      aneurysms.
AB  - A case of giant renal artery aneurysm in a 63-year-old man is presented. Renal
      artery aneurysms are rare (incidence of <1%) and this case is one of the largest
      giant renal artery aneurysms recorded in the literature. This case also
      demonstrates the value of multidetector spiral CT renal angiography (CTA) in the
      diagnosis, planning and treatment of renal aneurysms.

PMID- 16952021
TI  - Renal MR and CT angiography: current concepts.
AB  - During the past decade, noninvasive CTA and MRA imaging techniques have replaced
      catheter angiography for evaluation of the renal arteries. This article reviews
      techniques for optimizing renal MRA and CTA, assesses the advantages and
      limitations of MRA and CTA, and provides the current indications for renal
      vascular imaging including renal artery stenosis screening. New and future
      developments in these rapidly evolving techniques are also discussed.

PMID- 16952022
TI  - Clinical and therapeutic importance of sentinel node biopsy of the internal
      mammary chain in patients with breast cancer: a single-center study with long
      term follow-up.
AB  - BACKGROUND: We evaluated the incidence of sentinel lymph nodes (SLNs) in the
      internal mammary chain, calculated the lymphoscintigraphy and surgical detection
      rates, and evaluated the clinical effect on staging and the therapeutic approach
      in patients with breast cancer. METHODS: The study involved 741 women diagnosed
      with breast cancer eligible for the SLN technique. Lymphoscintigraphy was
      performed on the day before the operation by peritumoral injection of (99m)Tc
      labeled nanocolloid. During the operation, a gamma probe was used to detect the
      SLN, which was then removed. RESULTS: A total of 719 SLNs were found in the
      axillary chain and 72 in the internal mammary chain. Preoperative
      lymphoscintigraphy showed 107 hot spots in the internal mammary chain, but only
      72 SLNs in 65 patients were identified by the gamma probe and then removed with
      no complications. Of these 65 patients, 10 had a positive internal mammary chain
      SLN on final pathologic examination, whereas 55 patients had >or=1 negative SLNs
      on final pathologic analysis. Thirty-five (53%) of 65 patients had also an
      axillary SLN, but only 5 patients (8%) had a positive SLN on pathologic analysis.
      CONCLUSIONS: Evaluation of the SLNs in the internal mammary chain may provide
      more accurate staging in breast cancer patients. If an internal mammary sampling
      is not performed, patients may be understaged. This technique may allow better
      selection of those patients who will be submitted to adjuvant locoregional
      radiotherapy.

PMID- 16952023
TI  - Chemotherapy and regional therapy of hepatic colorectal metastases: expert
      consensus statement by Bartlett et al.

PMID- 16952024
TI  - Selection of patients for resection of hepatic colorectal metastases: expert
      consensus statement by Charnsangavej et al.

PMID- 16952025
TI  - AHPBA/SSO/SSAT Consensus Conference on hepatic colorectal metastases: rationale
      and overview of the conference. January 25, 2006.

PMID- 16952026
TI  - Significance of multiple lymphatic basin drainage in truncal melanoma patients
      undergoing sentinel lymph node biopsy.
AB  - BACKGROUND: Truncal melanoma involving metastases to multiple lymph node basins
      has a much worse prognosis than tumor involvement of a single lymph node basin.
      Recent results also suggest that, independently of the status of lymph node
      involvement, patients with multiple lymphatic basin drainage (MLBD) on
      lymphoscintigraphy have an increased risk of lymph node metastasis and a worse
      prognosis than those with a single lymphatic drainage basin. Because published
      reports have conflicting results, the authors compared their experience at the
      University of Michigan Comprehensive Cancer Center with recently published
      findings. METHODS: The authors searched a prospectively maintained melanoma
      database at the University of Michigan for patients with primary truncal melanoma
      who underwent lymphoscintigraphy and sentinel lymph node biopsy between 1997 and
      2004. The association of MLBD with the clinical and pathologic characteristics
      collected and the presence of regional metastases was tested by using contingency
      tables and the chi(2) test statistic and by using the Fisher's exact test
      statistic when cell frequencies were small. The product-limit method of Kaplan
      and Meier was used to estimate disease-free and overall survival probabilities.
      RESULTS: Of 423 patients with primary truncal melanoma who underwent sentinel
      lymph node biopsy, 123 (29%) had a positive result, and 98 patients (23.2%) had
      MLBD. Patients with tumors located in the middle of the trunk and tumor
      ulceration were more likely to have MLBD (P < .0001 and P = .045, respectively).
      Patients with a single lymphatic drainage basin and MLBD had a similar risk of
      lymph node metastasis and similar disease-free and overall survival. CONCLUSIONS:
      Patients with truncal melanomas tend to have MLBD when the tumor is located in
      the middle of the trunk or when ulceration is present. In our experience,
      drainage to multiple lymphatic basins was not an independent risk factor for
      sentinel lymph node metastasis and has no independent prognostic significance.

PMID- 16952027
TI  - Candidates for curative resection in advanced gastric cancer patients who had
      equivocal para-aortic lymph node metastasis on computed tomographic scan.
AB  - BACKGROUND: The aim of this study was to determine how to select potential
      candidates for curative resection among advanced gastric patients with equivocal
      findings of para-aortic lymph node metastasis on computed tomography (CT).
      METHODS: We analyzed the clinicopathologic results of 23 advanced gastric cancer
      patients who were diagnosed as having equivocal findings of para-aortic lymph
      node metastasis on a CT scan and who underwent gastrectomy with D2 and para
      aortic lymph node dissection. RESULTS: Twenty-two patients were male, and one
      patient was female. The median age of all study subjects was 52 years (range, 31
      75 years). Sixteen underwent total gastrectomy, and seven underwent subtotal
      gastrectomy. The median number of A2 (suprarenal) lymph nodes harvested was 2
      (range, 1-5), and that of B1 (infrarenal) lymph nodes was 6 (range, 1-17). Ten
      (43.5%) of the 23 patients were proven pathologically to have metastasis to para
      aortic lymph nodes. Two patients with cT2 cancer had no metastatic para-aortic
      lymph node, whereas three patients with cT4 disease had metastatic para-aortic
      lymph nodes (P = .021). Seven (70.0%) of 10 patients with pathologic para-aortic
      lymph node metastasis experienced recurrence, whereas only 2 (15.4%) of 13
      patients without experienced recurrence (P = .008). The Lauren classification was
      found to be an independent predictor of para-aortic lymph node metastasis
      (relative risk; .13; 95% confidence interval, .02-.83; P = .03). CONCLUSIONS:
      More than half of gastric cancer patients with equivocal findings of para-aortic
      lymph node metastasis on CT are potential candidates for curative resection. The
      Lauren classification of gastric cancer in patients with equivocal CT findings of
      para-aortic lymph node metastasis would be helpful when deciding on clinical
      stage and treatment plans in these patients.

PMID- 16952028
TI  - Clinical implications of microsomal prostaglandin e synthase-1 overexpression in
      human non-small-cell lung cancer.
AB  - BACKGROUND: Microsomal prostaglandin E synthase-1 (mPGES-1) has recently been
      found to overexpress in human cancers, including non-small-cell lung cancer
      (NSCLC). However, the clinical value is largely unknown. The aim of this study
      was to investigate the associations between mPGES-1 expression in NSCLC and the
      clinical characteristics and survival outcome. METHODS: Between 2001 and 2003,
      paired fresh tumorous and nontumorous samples were prospectively procured from
      patients undergoing surgery for NSCLC. The expression of mPGES-1 was assessed by
      using Western blot in 93 subjects and reverse transcriptase-polymerase chain
      reaction in 35. Overexpression of mPGES-1 was defined as a more than 2-fold
      expression in the tumorous sample compared with the corresponding nontumorous
      one. Immunohistochemistry was used to confirm its localization to the tumor
      cells. In a subset of 30 cases, cyclooxygenase-2 (COX-2) was also analyzed to
      assess its association with mPGES-1. RESULTS: The protein and messenger RNA of
      mPGES-1 were both expressed at higher levels in the tumor samples (P < .001 and P
      = .006, respectively). The expressions of mPGES-1 and COX-2 were unrelated (P =
      .715). Overexpression of mPGES-1 protein was observed in 61 (65.6%) of 93
      patients, but it was not significantly associated with the clinicopathologic
      characteristics or overall and disease-free survivals. However, mPGES-1
      overexpression seemed to be associated with the likelihood of subsequent
      pulmonary metastases and a lower tendency for developing bony metastases (P =
      .001 and P = .006, respectively). CONCLUSIONS: Our results demonstrated that
      mPGES-1 was overexpressed in NSCLC, unassociated with COX-2. Overexpression of
      mPGES-1 per se was not a prognostic indicator, but it might be implicated in the
      organ preference of metastasis.

PMID- 16952029
TI  - Genetic variation among different populations of Aster tripolium grown on
      naturally and anthropogenic salt-contaminated habitats: implications for
      conservation strategies.
AB  - The sea aster, Aster tripolium L., grows naturally in temperate regions, mainly
      in the salt meadows close to the coast. The species is also found in naturally
      and anthropogenically salt-contaminated inland habitats, such as potash mine
      dumps. The genetic relationships among populations from different habitats and
      correlations of the genotype with physiological and vegetational parameters were
      investigated. A. tripolium plants from five different sites close to the seashore
      on the North Sea island Baltrum, from five different potash mine dumps and, as an
      outgroup, from the seashore in Japan were probed. DNA was extracted from five
      plants from each of the 11 A. tripolium populations and analyzed for random
      amplified polymorphic DNA (RAPD). Altogether 35 polymorphic bands in 51
      individuals and 45 different detectable genotypes could be identified. For
      evaluation of the genetic variation using RAPD bands, the neighbor-joining
      method, the principal coordinate analysis, and the analysis of molecular variance
      were applied, resulting in the classification into three genetic groups. A.
      tripolium plants from different ecological habitats on Baltrum were closely
      related while the plants growing at the deposit dumps showed a higher genetic
      diversity. The Japanese population was genetically very different from the German
      populations. Correlations between phytosociological and soil parameters and the
      respective genotype were not significant. The results argue for a conservation of
      anthropogenically salt-contaminated habitats to maintain genetic variability not
      only on the species level, but also within a species.

PMID- 16952030
TI  - Pollen of Ceratostema (Ericaceae, Vaccinieae): tetrads without septa.
AB  - The pollen morphology of two species of the Neotropical genus Ceratostema
      (Ericaceae) was examined by light, scanning and transmission electron microscopy.
      The Ceratostema species examined have 3-colporate pollen grains united in
      permanent tetrahedral tetrads that show a common condition encountered in the
      Ericaceae. But the septal exine was absent between two neighboring grains in each
      pollen tetrad of Ceratostema. The pollen tetrads without septa are the first
      report for the Ericaceae as well as other angiosperm families.

PMID- 16952031
TI  - Characterization of two laccases of loblolly pine (Pinus taeda) expressed in
      tobacco BY-2 cells.
AB  - We previously showed that eight laccase genes (Lac 1-Lac 8) are preferentially
      expressed in differentiating xylem and are associated with lignification in
      loblolly pine (Pinus taeda) [Sato et al. (2001) J Plant Res 114:147-155]. In this
      study we generated transgenic tobacco suspension cell cultures that express the
      pine Lac 1 and Lac 2 proteins, and characterized the abilities of these proteins
      to oxidize monolignols. Lac 1 and Lac 2 enzymatic activities were detected only
      in the cell walls of transgenic tobacco cells, and could be extracted with high
      salt. The optimum pH for laccase activity with coniferyl alcohol as substrate was
      5.0 for Lac 1 and between 5.0 and 6.0 for Lac 2. The activities of Lac 1 and Lac
      2 increased as the concentration of CuSO(4) in the reaction mixtures increased in
      the range from 1 to 100 microM. Both enzymes were able to oxidize coniferyl
      alcohol and to produce dimers of coniferyl alcohol. These results are consistent
      with the hypothesis that Lac 1 and Lac 2 are involved in lignification in
      differentiating xylem of loblolly pine.

PMID- 16952032
TI  - Prediction of clinical outcome of fluoropyrimidine-based chemotherapy for gastric
      cancer patients, in terms of the 5-fluorouracil metabolic pathway.
AB  - Fluoropyrimidines are widely used in chemotherapy regimens for metastatic gastric
      cancer. Interindividual variation in the enzyme activity of the 5-fluorouracil
      (FU) metabolic pathway can affect the extent of 5-FU metabolism and affect the
      efficacy of 5-FU based chemotherapy. In this review, the role of the genetic
      factors affecting the therapeutic efficacy of fluoropyrimidines is discussed,
      with a special emphasis on enzymes involved in the 5-FU metabolic pathway. The
      gene expressions of thymidylate synthase, dihydropyrimidine dehydrogenase,
      thymidine phosphorylase, and orotate phosphoribosyltransferase are discussed in
      relation to the efficacy of fluoropyrimidine treatment for metastatic gastric
      cancer. These candidate genes, along with others yet to be identified, could
      allow accurate prediction of the clinical outcome in patients receiving
      fluoropyrimidine-based chemotherapy in the future. Well-designed and large
      prospective studies, which include relevant pharmacogenetic parameters, are
      needed to confirm the values required to predict clinical outcome.

PMID- 16952033
TI  - Gastric-and-intestinal mixed-type intestinal metaplasia: aberrant expression of
      transcription factors and stem cell intestinalization.
AB  - Helicobacter pylori plays a causative role in the development of chronic atrophic
      gastritis, intestinal metaplasia (IM), and stomach cancer. Although IM has long
      attracted attention as a putative preneoplastic lesion for stomach cancers, its
      clinicopathologic significance has yet to be clarified in detail. Using gastric
      and intestinal epithelial cell markers, IM was here divided into two major types:
      a gastric-and-intestinal (GI) mixed type and a solely intestinal (I) type. In the
      former, gastric and intestinal phenotypic markers appeared not only at the
      glandular but also at the cellular level. Furthermore, neuroendocrine cells also
      showed intestinalization along with their exocrine counterparts. In animal
      models, GI-type IM was found to appear first, followed by the solely I type.
      Summarizing these data, it was suggested that IM might be caused by the gradual
      intestinalization of stem cells from the GI to the I type. The molecular
      mechanisms of IM include the ectopic expression of CDX1, CDX2, OCT-1, and members
      of the Erk pathway. Suppression of the expression of gastric transcription
      factors such as SOX2, genes that are involved in the Sonic hedgehog pathway, and
      RUNX3, a tumor suppressor gene, could be additional relevant alterations. The
      expression of PDX1 may also be associated with pseudopyloric gland metaplasia and
      IM. Detailed analysis of gene regulation may shed light on the molecular bases of
      gastric lesions, leading to strategies for chemoprevention.

PMID- 16952034
TI  - Laparoscopic gastrectomy with lymph node dissection for gastric cancer.
AB  - Since 1991, laparoscopic surgery has been adopted for the treatment of gastric
      cancer, and it has been performed worldwide, especially in Japan and Korea. We
      reviewed the English-language literature to clarify the current status of and
      problems associated with laparoscopic gastrectomy with lymph node dissection as
      treatment for gastric cancer. In Japan, early-stage gastric cancer (T1/T2, N0) is
      considered the only indication for laparoscopic gastrectomy. As yet, there is
      little high-level evidence based on long-term outcome supporting laparoscopic
      gastrectomy for cancer, but reports have provided level 3 evidence that the
      procedure is technically safe, and that it yields better short-term outcomes than
      open surgery; that is, recovery is faster, hospital stay is shorter, there is
      less pain, and cosmesis is better. However, investigation into the oncological
      outcome of laparoscopic gastrectomy as treatment for cancer is lacking. To
      establish laparoscopic surgery as a standard treatment for gastric cancer,
      multicenter randomized controlled trials to compare the short- and long-term
      outcomes of laparoscopic surgery versus open surgery are necessary.

PMID- 16952035
TI  - Gastric-type well-differentiated adenocarcinoma and pyloric gland adenoma of the
      stomach.
AB  - Since 1985, when gastric-type well-differentiated adenocarcinomas were
      demonstrated in hyperplastic polyps of the stomach, we have studied phenotypic
      expression in gastrointestinal epithelial lesions. The recent discovery of MUC
      genes coding core proteins of mucin has improved research on the phenotypic
      expression of gastrointestinal neoplasms. The disease entity of gastric-type well
      differentiated adenocarcinoma has recently been accepted, especially in Japan and
      Europe. This entity has often become a clinicopathological subject of discussion,
      because its biological behavior is possibly highly malignant, in spite of the
      difficulty in making endoscopic and histopathological diagnoses. Even under these
      circumstances, the term "gastric adenoma" usually means flat adenoma of the
      intestinal type. Gastric-type adenomas have been regarded as exceptional until
      recently. Although gastric-type adenomas could theoretically be classified into
      foveolar type and pyloric-gland type, foveolar-type adenoma is, in practice,
      difficult to distinguish from gastric-foveolar-type adenocarcinoma. In 2003, we
      first reported systematic clinicopathological analyses of pyloric gland adenoma,
      demonstrating its unstable and precancerous nature. In this article, we review
      and discuss the clinicopathological and molecular pathological aspects of gastric
      type well-differentiated adenocarcinomas and pyloric gland adenomas, mainly based
      on our published and unpublished data.

PMID- 16952036
TI  - A phase II study of combined chemotherapy with methotrexate, 5-fluorouracil, and
      low-dose cisplatin (MFP) for histologically diffuse-type advanced and recurrent
      gastric cancer (KDOG9501).
AB  - BACKGROUND: Histologically diffuse-type gastric cancer is well known to have a
      poor prognosis and is often complicated with abdominal and pleural effusions. We
      evaluated the efficacy of a low dose of cisplatin combined with methotrexate and
      5-fluorouracil (MFP therapy) in diffuse-type advanced gastric cancer. METHODS:
      The study group comprised 47 patients. Patients with pleural effusion or ascites
      were actively enrolled. Methotrexate (30 mg/m(2) per day) plus 5-fluorouracil
      (600 mg/m(2) per day) was administered on days 1 and 8. Cisplatin (6 mg/m(2) per
      day) was given daily for 14 days after which there was 14 day's rest. Calcium
      leucovorin (15 mg) was administered after methotrexate. RESULTS: The overall
      response rate was 38.3%. Ascites disappeared or decreased in 15 of 23 patients
      (disappeared in 9). Pleural effusion disappeared or decreased in 6 of 8 patients
      (disappeared in 4). Of the 21 patients with poor oral intake at study entry, 15
      (71.4%) were able to orally ingest food. Hematologic toxicity of grade 3 or
      higher comprised leukopenia in 10 patients (21.3%) and neutropenia in 9 (19.1%).
      Nonhematologic toxicity included anorexia and nausea/vomiting, in 1 patient each
      (2.1%). The median survival time was 211 days. CONCLUSION: MFP therapy is useful
      for the management of diffuse-type inoperable and recurrent gastric cancer, even
      in patients with conditions such as pleural effusion, ascites, or lymphangitis
      carcinomatosa who have a poor prognosis or cannot eat solid food.

PMID- 16952037
TI  - Usefulness of preoperative FDG-PET for detection of gastric cancer.
AB  - BACKGROUND: Positron emission tomography (PET), using 18F-fluoro-2-deoxy-D
      glucose (FDG) as a tracer, can detect malignant neoplasms with altered glucose
      metabolism. To clarify the usefulness of FDG-PET for detecting gastric cancer, we
      evaluated preoperative PET imaging in gastric cancer patients. METHODS: Sixty-two
      gastric cancer patients who underwent FDG-PET imaging and gastric resection with
      lymphadenectomy were evaluated. RESULTS: For primary tumor assessment by PET,
      detection rates were significantly different in the following order: tumor size
      30 mm or more (76.7%) > tumor size less than 30 mm (16.8%); advanced gastric
      cancer (AGC, 82.9%) > early gastric cancer (EGC; 25.9%); with nodal involvement
      (79.3%) > without nodal involvement (39.4%). In EGCs, the detection rate of the
      intestinal type, according to Lauren's classification (43.8%) was significantly
      higher than that of the diffuse type (0%). Two of the 7 EGC patients who were PET
      positive had nodal involvement and their tumors were the intestinal type. For the
      assessment of nodal involvement, the accuracy of nodal involvement detection was
      67.7% with PET and 75.8% with computed tomography (CT). Preoperative FDG-PET
      revealed colon cancer in 2 patients, adrenal tumor in 1 patient, lung cancer in 1
      patient, and lung metastasis in 1 patient. CONCLUSION: Larger or more advanced
      tumors with nodal involvement had a higher detection rate by PET. In EGCs, only
      the intestinal type was detectable by PET. PET-positive EGC may be aggressive,
      and an adequate lymphadenectomy must be done. Preoperative PET was useful for the
      detection of other malignancies and distant metastasis.

PMID- 16952038
TI  - Assessment of lymph node micrometastasis in early gastric cancer in relation to
      sentinel nodes.
AB  - BACKGROUND: The development of endoscopic resection and reduced surgical
      procedures has progressed in recent years. Lymph node micrometastases can be
      cited as one of the problems with reduced operations. In this study, we
      investigated clinicopathological findings and sentinel lymph nodes (SNs) for
      associations with micrometastases. We discuss the indications for endoscopic
      mucosal resection (EMR), reduced surgery, and sentinel node navigation surgery
      (SNNS) based on the results. METHODS: Immunostaining with anti-cytokeratin
      antibodies was used as the method of exploring for micrometastases. Comparisons
      and assessments were made in regard to the presence or absence of micrometastases
      and various clinicopathological factors. RESULTS: The relationship between the
      clinicopathological factors and micrometastases was investigated in 120 patients
      with pT1pN0 gastric cancer. Significant differences in depth of invasion (mucosal
      [m] versus submucosal [sm]) and histological type (differentiated versus
      undifferentiated) were observed in both univariate analysis and multivariate
      analysis. Micrometastases were observed in 32% of the sm cancers, and they were
      observed in group 2 lymph nodes (no. 7) in 8%. They tended to be more common in
      the undifferentiated type. The micrometastatic lymph nodes were restricted to
      blue nodes (BNs) and lymph nodes within the dye flow area of patent blue (used
      intraoperatively explore for SNs). CONCLUSION: It is considered that the
      indications for current EMR and reduced surgery in early gastric cancer are valid
      from the standpoint of micrometastases. But if the SNNS that has been studied in
      recent years is introduced, the lymphatic basin dissection method seems valid
      only if the case is s-pN0 early cancer.

PMID- 16952039
TI  - Combination chemotherapy with irinotecan and cisplatin in pretreated patients
      with unresectable or recurrent gastric cancer.
AB  - BACKGROUND: The combination of irinotecan (CPT-11) and cisplatin (CDDP) is an
      active regimen for metastatic gastric cancer in the first-line setting. The
      objective of this retrospective study was to clarify its efficacy and safety in
      patients with prior chemotherapy for advanced or recurrent gastric cancer.
      METHODS: Patients in the study fulfilled the following selection criteria: (1)
      histologically proven gastric cancer with metastatic lesions; (2) performance
      status of 2 or less; (3) age of 75 years or younger; (4) at least one prior
      chemotherapy regimen without CPT-11 or CDDP; (5) adequate bone marrow, liver, and
      kidney function; (6) normal cardiac function; (7) no other severe medical
      conditions; (8) no other active malignancy; and (9) the provision of written
      informed consent. The treatment consisted of CPT-11 (70 mg/m2) on day 1 and day
      15 and CDDP (80 mg/m2) on day 1; repeated every 4 weeks. RESULTS: Thirty-two
      patients were recruited, and 28 were assessable for clinical response. There were
      eight partial responses, resulting in a response rate of 28%. Median time to
      progression was 104 days (range, 24-863 days) and median overall survival time
      was 283 days from the initiation of this therapy. The incidences of grade 4
      neutropenia, grade 3 or higher infection, and diarrhea were 69%, 9%, and 3%,
      respectively. Other adverse reactions were mild. No treatment-related deaths
      occurred. CONCLUSION: A combination of CPT-11 and CDDP may be active and feasible
      for gastric cancer patients with prior chemotherapy. Further studies with larger
      numbers of patients are needed to clarify this regimen's significance in the
      second-line setting.

PMID- 16952040
TI  - Community-based familial study of Helicobacter pylori infection among healthy
      Japanese Brazilians.
AB  - BACKGROUND: The present study of Helicobacter pylori infection was conducted in
      family units of Japanese Brazilians living in Sao Paulo city. The authors
      attempted to determine the seroprevalence of H. pylori infection within family
      units of Japanese Brazilians and to identify risk factors associated with
      intrafamilial transmission. METHODS: The seroprevalence was determined in 1037
      healthy and asymptomatic volunteer subjects aged 0-69 years (530 adults and 507
      children) of 265 families. Demographic data and details of living conditions were
      obtained from each family. RESULTS: H. pylori seropositive infection was found in
      39.2% of the parents and 9.3% of the children. A reduced risk of H. pylori
      infection was found for girls (odds ratio [OR] 0.45; 95% confidence interval
      [CI], 0.23-0.86). The prevalence of infection was 3.5% for children with
      uninfected parents; 9.9% (OR, 2.51; 95% CI, 0.95-6.61) for those with a
      seronegative mother and a seropositive father; 14.9% (OR, 4.93; 95% CI, 1.86
      13.06) for those with a seropositive mother and a seronegative father; and 16.0%
      (OR, 5.29; 95% CI, 1.98-14.14) for those with seropositive parents. On
      multivariate analysis, the use of a pacifier, and mother's symptoms of nausea and
      vomiting were significantly associated with the risk of H. pylori infection for
      children, and the child having her/his own room was significantly associated with
      a reduced risk. Income was not associated with H. pylori infection in children
      and was inversely associated in parents. CONCLUSION: The prevalence of H. pylori
      infection in family units of Japanese Brazilians supports the hypothesis of a
      predominant role for mother-child transmission of H. pylori infection, mainly
      through contact with regurgitated gastric juice in the mother's mouth.

PMID- 16952041
TI  - Relative value of repeat gastric ulcer surveillance gastroscopy in diagnosing
      gastric cancer.
AB  - BACKGROUND: Gastric cancer can present with the endoscopic appearances of a
      benign gastric ulcer (GU). Opinion remains divided on the need for follow-up of
      patients diagnosed with GU, and the aim of this study was to examine the long
      term outcomes of patients whose GU proved malignant on follow-up gastroscopy.
      METHODS: Between October 1, 1995, and September 30, 2003, 25,579 gastroscopies
      were performed in one unit. These identified 544 patients with apparently benign
      GU, of whom 277 (51%) underwent 334 elective follow-up endoscopies. Twelve of
      these patients (4.3%) were shown to have a malignant ulcer; their outcomes were
      compared to those of the 296 other patients diagnosed with gastric cancers in
      this time frame. RESULTS: The patients in the GU cancer group had earlier stage
      disease (stage I, 33% vs 6.4%; chi2 = 11.2; DF1; P = 0.001), and were more likely
      to undergo R0 gastrectomy (50% vs 30%; chi2 = 2.064; DF1; P = 0.151) and to
      survive long term (46% vs 16%; log-rank chi2, 5.79; DF1; P = 0.0162) than
      patients in the comparison cohort. CONCLUSION: Gastroscopic follow-up of 50
      patients with an apparently benign GU will identify 1 patient with a malignancy
      destined to survive for 5 years following R0 gastrectomy. This justifies the
      diagnostic effort of repeat gastroscopy to ensure complete healing of GU.

PMID- 16952042
TI  - Intratumoral heterogeneity of MIB-1 labelling index in gastric gastrointestinal
      stromal tumor (GIST).
AB  - BACKGROUND: The MIB-1 labelling index (LI) is used as a prognostic indicator for
      gastrointestinal stromal tumors (GISTs). However, whether a biopsy-based LI
      represents the entire tumor is uncertain, because the LI is not always
      homogeneous. In this study, we examined the extent and characteristics of LI
      heterogeneity in gastric GISTs. METHODS: We analyzed ten c-kit-positive gastric
      GISTs with diameters exceeding 3 cm, of which six were multilobular and four were
      unilobular. For MIB-1-immunostained sections, continuous digital images were
      obtained through the maximum diameter of the lobules. We obtained LIs for images
      by carrying out computer-assisted image analysis, and calculated the means and
      standard deviations (SDs) of the LIs for the lobules. For each lobule,
      intralobular heterogeneity was evaluated on the basis of the SD. For multilobular
      tumors, interlobular heterogeneity was assessed on the basis of the mean LI
      difference between lobules. RESULTS: The SDs, which ranged from 0.8% to 9.8%,
      indicated intralobular heterogeneity. Moreover, considerable interlobular
      heterogeneity was noted in five (83%) of the six multilobular GISTs, in which the
      maximum interlobular mean LI difference ranged from 9.6% to 27.2%. Notably,
      although the high maximum mean LI (14.1%-32.3%) showed that these five GISTs were
      high-grade tumors, they also contained at least one lobule showing a low-grade
      mean LI value (2.7%-5.1%). CONCLUSION: Gastric GISTs often show intralobular or
      interlobular MIB-1 LI heterogeneity. In multilobular GISTs, multiple biopsy
      samples may be required for the accurate evaluation of tumor grade.

PMID- 16952044
TI  - Recurrent gastrointestinal stromal tumor (GIST) of the stomach associated with a
      novel c-kit mutation after imatinib treatment.
AB  - A 57-year-old man with gastrointestinal stromal tumor (GIST) of the stomach with
      peritoneal dissemination underwent gastrectomy. After surgery, he was treated
      with 400 mg/day of imatinib, without recurrence, for 26 months. At 26 months, the
      imatinib dose was reduced because of nausea, and 4 months after the dose
      reduction, recurrence of GIST was detected, for which surgical resection was
      performed again. The first surgical specimen had a mutation of exon 11 in the c
      kit receptor gene. Intriguingly, the second surgical specimen had a novel
      mutation of exon 17, in addition to the above-mentioned mutation, in the c-kit
      receptor gene. Based on the result of molecular analysis, the novel mutation of
      exon 17, induced by longterm chemotherapy, was judged to have been responsible
      for the recurrence, which perhaps was triggered by the dose reduction of
      imatinib.

PMID- 16952043
TI  - Helicobacter pylori-negative / API2-MALT1 translocation-negative low-grade MALT
      lymphoma.
AB  - A 71-year-old man with a Helicobacter pylori infection-negative and API2-MALT1
      translocation-negative extranodal marginal-zone B-cell lymphoma of mucosa
      associated lymphoid tissue (MALT) type of the stomach has been followed
      conservatively for over 5 years. The lesion has shown no major morphological
      changes or malignant progression into a diffuse large-cell type during the time
      course. The absence of genetic translocation of API2-MALT1 was confirmed with
      fluorescence in situ hybridization (FISH). The prognosis of H. pylori-negative
      and API2-MALT1 translocation-negative low-grade MALT lymphoma is unknown, and a
      standard treatment for such lymphoma has yet to be defined. The case of MALT
      lymphoma negative for both of the above factors that we report has shown no
      obvious rapid progression or malignant change over the long-term course. Although
      curative operation and/or chemoradiotherapy should still be discussed as the
      treatment of choice, the treatment of this type of lymphoma must be carefully
      determined on a case-by-case basis, according to its biological status and
      prognosis.

PMID- 16952045
TI  - Population-attributable fractions in gastric cancer risk factors: the necessity
      to focus on Helicobacter pylori infection.

PMID- 16952046
TI  - The effect of preoperative radiotherapy and reconstructive surgery on wound
      complications after resection of extremity soft-tissue sarcomas.
AB  - BACKGROUND: Major wound complications (MWCs) are frequent after preoperative
      radiotherapy (RT) for extremity soft-tissue sarcoma (STS). We examined the rate
      of MWCs at a single institution with readily available reconstructive surgery.
      METHODS: The medical records of consecutively treated extremity STS patients
      treated with preoperative external-beam RT and surgical resection from June 1996
      through February 2003 were reviewed. Patients underwent RT (median 50 Gy),
      followed by resection 4-8 weeks later. Patients believed to be at higher risk for
      MWC underwent wound closure by the reconstructive surgery service (RSS). MWCs
      included secondary operation, invasive procedure, hospital readmission, or
      persistent deep packing or dressing changes. RESULTS: A total of 173 patients
      underwent preoperative RT. Median age was 54 years; 51% were female; 80% had
      lower extremity STS. Wound closure was performed by the primary surgeon in 91
      cases (53%). The RSS performed wound closure in the remaining 82 patients (47%).
      One or more MWCs occurred in 55 patients (32%). Wound complications were more
      likely in patients with lower extremity (49/138, 36%) than upper extremity (6/35,
      17%) STS (P = 0.03). Among patients with lower-risk wounds closed by the primary
      surgical team, 29 (32%) experienced MWC, whereas in the higher-risk patients
      closed by the RSS, MWC occurred in 26 (32%). CONCLUSIONS: MWCs are frequent after
      preoperative RT and occur more commonly in patients with lower extremity tumors.
      The MWC rate observed in a single-institution setting was comparable to that
      observed in the preoperative therapy arm of a multicenter Canadian trial.
      Patients believed to be at higher risk for MWCs undergoing RSS closure have MWC
      rates comparable to those with lower-risk wounds closed by the primary team.

PMID- 16952048
TI  - The identification of chemical intermediates in enzyme catalysis by the rapid
      quench-flow technique.
AB  - Traditionally, enzyme transient kinetics have been studied by the stopped-flow
      and rapid quench-flow (QF) methods. Whereas stopped-flow is the more convenient,
      it suffers from two weaknesses: optically silent systems cannot be studied, and
      when there is a signal it cannot always be assigned to a particular step in the
      reaction pathway. QF is a chemical sampling method; reaction mixtures are aged
      for a few milliseconds or longer, 'stopped' by a quenching agent and the product
      or the intermediate is measured by a specific analytical method. Here we show
      that by exploiting the array of current analytical methods and different
      quenching agents, the QF method is a key technique for identifying, and for
      characterising kinetically, intermediates in enzyme reaction pathways and for
      determining the order by which bonds are formed or cleaved by enzymes acting on
      polymer substrates such as DNA.

PMID- 16952047
TI  - Depletion of CD4+CD25+ regulatory T cells promotes a tumor-specific immune
      response in pancreas cancer-bearing mice.
AB  - BACKGROUND: Pancreas cancer-bearing mice have an increased prevalence of
      immunosuppressive CD4(+)CD25(+) regulatory T cells (T(reg)). Depletion of T(reg)
      results in smaller tumors and prolonged host survival. The objective of this
      study was to evaluate the tumor-specific immune response after depletion of
      T(reg) alone or in combination with a cancer vaccine. METHODS: Four groups of
      C57BL/6 mice were challenged with pancreas adenocarcinoma cells (Pan02). The mice
      received four combinations of antibody-mediated T(reg) depletion and whole tumor
      cell vaccination: (1) no treatment, (2) T(reg) depletion only, (3) vaccination
      only, or (4) T(reg) depletion and vaccination. Splenocytes and lymphocytes from
      tumor-draining lymph nodes were analyzed for tumor-specific release of interferon
      gamma by enzyme-linked immunosorbent spot assay. RESULTS: In T(reg)-depleted and
      vaccinated mice, a strong statistical trend toward smaller tumors (P = .05) and
      longer survival (P = .054) was found compared with untreated mice. T(reg)
      depleted mice showed significantly more tumor-specific cells than undepleted mice
      (P = .02). The number of tumor-specific cells was significantly higher in tumor
      draining lymph nodes than in the spleen (P = .002). Similarly, significantly more
      tumor-specific cells were found in spleens of T(reg)-depleted and vaccinated mice
      than in vaccinated-only mice (P = .009). CONCLUSIONS: Depletion of T(reg) alone
      or in combination with a whole tumor cell vaccine promotes a tumor-specific
      immune response. Thus, strategies incorporating T(reg) depletion might improve
      the efficacy of cancer vaccines.

PMID- 16952049
TI  - The insulysin (insulin degrading enzyme) enigma.

PMID- 16952050
TI  - Impact of biofilm matrix components on interaction of commensal Escherichia coli
      with the gastrointestinal cell line HT-29.
AB  - Commensal Escherichia coli form biofilms at body temperature by expressing the
      extracellular matrix components curli fimbriae and cellulose. The role of curli
      fimbriae and cellulose in the interaction of commensal E. coli with the
      intestinal epithelial cell line HT-29 was investigated. Expression of curli
      fimbriae by the typical commensal isolate E. coli TOB1 caused adherence and
      internalization of the bacteria and triggered IL-8 production in HT-29 cells. In
      particular, induction of IL-8 production was complex and involved curli-bound
      flagellin. While cellulose alone had no effect on the interaction of TOB1 with HT
      29 cells, co-expression of cellulose with curli fimbriae decreased adherence to,
      internalization and IL-8 induction of HT-29 cells. Investigation of a panel of
      commensal isolates showed a partial correlation between expression of curli
      fimbriae and enhanced internalization and IL-8 production. In addition, a high
      immunostimulatory flagellin was identified. Thus, the consequences of expression
      of extracellular matrix components on commensal bacterial-host interactions are
      complex.

PMID- 16952051
TI  - Control of methionine biosynthesis genes by protein kinase CK2-mediated
      phosphorylation of Cdc34.
AB  - Methionine and metabolites such as S-adenosylmethionine (AdoMet) are of vital
      importance for eukaryotes; AdoMet is the main donor of methyl groups and is
      involved in expression control of the methionine biosynthesis genes (MET genes).
      Genome-wide expression profiling of protein kinase CK2 deletion strains of the
      budding yeast Saccharomyces cerevisiae has indicated a function for CK2 in MET
      gene control. Deletion of the regulatory CK2 subunits leads to MET gene
      repression, presumably due to an impaired phosphorylation of the ubiquitin
      conjugating enzyme Cdc34, which controls the central MET gene transcription
      factor Met4. We show that CK2 phosphorylates Cdc34 at two sites and one of these,
      Ser282, has a significant impact on MET gene expression in vivo, and that high
      AdoMet levels inhibit CK2. The data provide evidence for a control of MET gene
      expression by protein kinase CK2-mediated phosphorylation of Cdc34, and appear to
      suggest a feedback control loop in which high AdoMet-levels are limiting CK2
      activity and thus MET gene expression.

PMID- 16952052
TI  - The diversity of the DnaJ/Hsp40 family, the crucial partners for Hsp70
      chaperones.
AB  - DnaJ/Hsp40 (heat shock protein 40) proteins have been preserved throughout
      evolution and are important for protein translation, folding, unfolding,
      translocation, and degradation, primarily by stimulating the ATPase activity of
      chaperone proteins, Hsp70s. Because the ATP hydrolysis is essential for the
      activity of Hsp70s, DnaJ/Hsp40 proteins actually determine the activity of Hsp70s
      by stabilizing their interaction with substrate proteins. DnaJ/Hsp40 proteins all
      contain the J domain through which they bind to Hsp70s and can be categorized
      into three groups, depending on the presence of other domains. Six DnaJ homologs
      have been identified in Escherichia coli and 22 in Saccharomyces cerevisiae.
      Genome-wide analysis has revealed 41 DnaJ/Hsp40 family members (or putative
      members) in humans. While 34 contain the typical J domains, 7 bear partially
      conserved J-like domains, but are still suggested to function as DnaJ/ Hsp40
      proteins. DnaJA2b, DnaJB1b, DnaJC2, DnaJC20, and DnaJC21 are named for the first
      time in this review; all other human DnaJ proteins were dubbed according to their
      gene names, e.g. DnaJA1 is the human protein named after its gene DNAJA1. This
      review highlights the progress in studying the domains in DnaJ/Hsp40 proteins,
      introduces the mechanisms by which they interact with Hsp70s, and stresses their
      functional diversity.

PMID- 16952053
TI  - Biology of the CAPA peptides in insects.
AB  - CAPA peptides have been isolated from a broad range of insect species as well as
      an arachnid, and can be grouped into the periviscerokinin and pyrokinin peptide
      families. In insects, CAPA peptides are the characteristic and most abundant
      neuropeptides in the abdominal neurohemal system. In many species, CAPA peptides
      exert potent myotropic effects on different muscles such as the heart. In others,
      including blood-sucking insects able to transmit serious diseases, CAPA peptides
      have strong diuretic or anti-diuretic effects and thus are potentially of medical
      importance. CAPA peptides undergo cell-type-specific sorting and packaging, and
      are the first insect neuropeptides shown to be differentially processed. In this
      review, we discuss the current knowledge on the structure, distribution,
      receptors and physiological actions of the CAPA peptides.

PMID- 16952054
TI  - Focal and segmental glomerulosclerosis.
AB  - An increasing cause of end-stage renal disease is the pathological lesion focal
      and segmental glomerulosclerosis (FSGS). FSGS is characterized by proteinuria and
      frequently nephrotic syndrome with ensuing renal failure. The etiology remains
      unknown in the majority of individuals. The idiopathic form of FSGS is most
      common; however, secondary forms of FSGS do exist. There is a form of FSGS that
      is fulminant that frequently recurs after renal transplantation with an estimated
      frequency of approximately 30%, suggesting that the pathogenesis is not solely a
      result of intrinsic kidney disease. Recently, hereditary forms of the disease
      were recognized as well as those associated with other congenital syndromes.
      Known genetic causes of the hereditary form of this disease have been suggested
      to account for upwards of 18% of cases. This review will address recent
      discoveries of the genetic mechanisms of hereditary FSGS and the current
      interpretations of their interactions at the slit diaphragm.

PMID- 16952055
TI  - Aneuploidy in the normal and diseased brain.
AB  - The brain is remarkable for its complex organization and functions, which have
      been historically assumed to arise from cells with identical genomes. However,
      recent studies have shown that the brain is in fact a complex genetic mosaic of
      aneuploid and euploid cells. The precise function of neural aneuploidy and
      mosaicism are currently being examined on multiple fronts that include
      contributions to cellular diversity, cellular signaling and diseases of the
      central nervous system (CNS). Constitutive aneuploidy in genetic diseases has
      proven roles in brain dysfunction, as observed in Down syndrome (trisomy 21) and
      mosaic variegated aneuploidy. The existence of aneuploid cells within normal
      individuals raises the possibility that these cells might have distinct functions
      in the normal and diseased brain, the latter contributing to sporadic CNS
      disorders including cancer. Here we review what is known about neural aneuploidy,
      and offer speculations on its role in diseases of the brain.

PMID- 16952056
TI  - Perlecan: how does one molecule do so many things?
AB  - Perlecan is a large multi-domain extracellular matrix proteoglycan that plays a
      crucial role in tissue development and organogenesis. In vertebrates, perlecan
      functions in a diverse range of developmental and biological processes, from the
      establishment of cartilage to the regulation of wound healing. How can a single
      molecule modulate such a wide variety of processes? We suggest that perlecan
      employs the same basic mechanism, based on interactions with growth factors,
      morphogens and matrix proteins, to regulate each of these processes and that the
      local extracellular environment determines the function of perlecan and
      consequently its downstream effects on the structure and function of the organ.
      We discuss this hypothesis in relation to its role in three major vertebrate
      developmental processes: angiogenesis, chondrogenesis and endochondral
      ossification.

PMID- 16952057
TI  - Leukocyte recruitment in atherosclerosis: potential targets for therapeutic
      approaches?
AB  - Atherosclerosis is a complex inflammatory disease involving cellular migration
      and interaction. Vascular injury in response to different cardiovascular risk
      factors enhances endothelial dysfunction, which in turn promotes the expression
      of inflammatory markers and transendothelial leukocyte migration. Recruitment of
      leukocytes from the blood stream into the vessel intima is a crucial step for the
      development of the disease. Recent findings have highlighted the role of
      chemokines, chemokine receptors, adhesion molecules, and gap junctions in this
      process by acting as chemoattractant, adhesive, or intercellular communication
      molecules. In this short review, we summarize new data concerning the different
      steps from leukocyte arrest to transendothelial migration and discuss potential
      new therapeutic approaches concerning these processes.

PMID- 16952058
TI  - Peutz-Jeghers syndrome: clinicopathology and molecular alterations.
AB  - Peutz-Jeghers syndrome (PJS, OMIM 175200) is an unusual inherited intestinal
      polyposis syndrome associated with distinct peri-oral blue/black freckling.
      Variable penetrance and clinical heterogeneity make it difficult to determine the
      exact frequency of PJS. PJS is a cancer predisposition syndrome. Affected
      individuals are at high risk for intestinal and extra-intestinal cancers. In
      1997, linkage studies mapped PJS to chromosome 19p, and subsequently a
      serine/threonine kinase gene defect (LKB1) was noted in a majority of PJS cases.
      A phenotypically similar syndrome has been produced in an LKB1 mouse knockout
      model. Several PJS kindred without LKB1 mutations have been described, suggesting
      other PJS loci. The management of PJS is complex and evolving. New endoscopic
      technologies may improve management of intestinal polyposis. Identification of
      specific genetic mutations and their targets will more accurately assess the
      clinical course, and help gage the magnitude of cancer risk for affected
      individuals.

PMID- 16952059
TI  - Kallmann's syndrome, a neuronal migration defect.
AB  - Infertility and inability to smell are the phenotypical features of Kallmann's
      syndrome (KS), a genetic disease which affects 1 in 10,000 males and 1 in 50,000
      females, the majority of the cases being sporadic. The molecular pathogenesis of
      KS is complex but mainly referable to the impairment of olfactory axon
      development and of the migration of gonadotropin-releasing hormone (GnRH)
      neurons. Only two different genes have been identified so far as responsible for
      the disease: KAL1 and KAL2, encoding anosmin-1 and fibroblast growth factor
      receptor 1 (FGFR1), respectively. In this review we focus our attention on
      insights evoked by recent studies, which propose a new direct role for anosmin-1
      in the migration GnRH neurons, and a fascinating hypothesis of interactions
      between anosmin-1 and FGFR1 systems.

PMID- 16952060
TI  - IUPHAR 2006--15th World Congress of Pharmacology. Pharmacology in the 21st
      Century: a bridge between the past and the new molecular frontiers. 2-7 July
      2006, Beijing, China.

PMID- 16952061
TI  - IUPHAR 2006--15th World Congress of Pharmacology. Metalloproteinases as
      Therapeutical Targets for Cancer Therapy. 2-7 July 2006, Beijing, China.

PMID- 16952062
TI  - IUPHAR 2006--15th World Congress of Pharmacology. Antibody-based therapies and
      diagnostics. 2-7 July 2006, Beijing, China.

PMID- 16952063
TI  - Medicinal Chemistry--30th National Symposium. 26-30 June 2006, Seattle, WA, USA.

PMID- 16952064
TI  - Natural Products in Drug Discovery & Development II--2nd annual Taylor & Francis
      conference. 21-22 June 2006, London, UK.

PMID- 16952065
TI  - Associated Professional Sleep Societies--SLEEP 2006 20th Anniversary Meeting. 17
      22 June 2006, Salt Lake City, UT, USA.

PMID- 16952066
TI  - Depression and Anxiety--SMi's second conference. 28-29 June 2006, London, UK.

PMID- 16952067
TI  - Beyond Genome 2006--a CHI meeting. DNA and protein biomarkers. 19-21 June 2006,
      San Francisco, CA, USA.

PMID- 16952068
TI  - Antimicrobial Resistance--2006 Annual Conference. Science--prevention--control.
      26-28 June 2006, Bethesda, MD, USA.

PMID- 16952069
TI  - Avian Influenza in Humans--First Annual Conference. Latest advances on
      prevention, therapies and protective measures. 29-30 June 2006, Paris, France.

PMID- 16952070
TI  - Current status of biomarkers for melanoma metastasis.
AB  - There is a critical unmet need for new predictive and prognostic biomarkers for
      melanoma. This feature presents a brief overview of the opportunities and
      challenges facing investigators who are seeking biomarkers that can predict those
      melanomas that are likely to result in progression (metastasis) and death.
      Melanoma metastasis to the regional lymph nodes is now readily identified by
      sentinel node biopsy. However, currently available prognostic factors, which are
      based on clinical parameters and histological findings in the primary tumor, are
      limited in their ability to reliably discriminate which patients will manifest
      sentinel node metastasis and/or disseminated disease. To date, even those
      biomarkers for which substantial clinical correlation has been obtained have
      suffered from both conflicting data in clinical trials involving different
      patient populations and poorly understood interactions between the biomarkers and
      other established prognostic factors. An understanding of whether biomarker data
      should be viewed as a continuum or be categorized based on discrete breakpoints
      is also frequently lacking. In many cases, biomarkers are initially developed
      based on unequivocal index cases, such as clearly benign or clearly malignant
      melanocytic lesions, but then fail as predictive tools when applied to the more
      difficult cases that arise in clinical practice; such cases occupy a 'gray' zone
      that is filled with uncertainty and lacks an established 'gold standard' against
      which a biomarker prediction can be validated.

PMID- 16952071
TI  - Real-time subcellular imaging in live animals: new visible targets for cancer
      drug discovery.
AB  - This feature describes new in vivo imaging technology to visualize and identify
      novel targets for cancer drug discovery. AntiCancer Inc has developed dual-color
      fluorescent cells, with one color in the nucleus and another color in the
      cytoplasm, that enable visualization of real-time nuclear-cytoplasmic dynamics in
      living cells in vivo and in vitro, as well as nuclear dynamics and simultaneous
      cell and nuclear shape change. To obtain the dual-color cells, red fluorescent
      protein (RFP) was expressed in the cytoplasm of human and rodent cancer cells,
      and green fluorescent protein (GFP) that was linked to histone H2B was expressed
      in the nucleus. The migration velocities of the dual-color cancer cells in the
      capillaries were measured by capturing images of the fluorescent cells over time.
      The cells and nuclei in the capillaries were shown to elongate to fit the width
      of these vessels. Cancer cells in capillaries that were more than 8 mm in
      diameter were found to migrate. During extravasation, real-time imaging
      demonstrated that cytoplasmic processes of certain cancer cells exited the
      vessels first, with the nuclei then following along the cytoplasmic projections.
      Both the cytoplasm and nuclei underwent deformation during extravasation.
      Different cancer cell lines appear to vary strongly in their ability to
      extravasate. With the dual-color cancer cells and a highly sensitive whole-mouse
      imaging system (Olympus OV100), the subcellular dynamics of cancer metastasis can
      now be visualized in live mice. Further developments in subcellular imaging in
      live animals is expected to result in a new 'in vivo cell biology' that will
      provide visible targets for cancer and other diseases.

PMID- 16952072
TI  - Drug evaluation: AP-23573--an mTOR inhibitor for the treatment of cancer.
AB  - ARIAD Pharmaceuticals Inc is developing intravenous and oral formulations of AP
      23573, a rapamycin analog and inhibitor of mTOR (mammalian target of rapamycin)
      that blocks the proliferation and migration of vascular smooth muscle cells, for
      the potential treatment of cancer, including solid and hematological forms.

PMID- 16952075
TI  - [Tracheotomy-endoscop for dilatational percutaneous tracheotomy (TED)].
AB  - While surgical tracheotomies are currently performed using state-of-the-art
      operative techniques, percutaneous dilatational tracheostomy (PDT) is in a
      rapidly evolving state with regard to its technology and the number of techniques
      available. This has resulted in a range of new complications that are difficult
      to quantify on a scientific basis, given the fact that more than half of the
      patients who are tracheotomized in intensive care units die from their underlying
      disease. The new Tracheotomy Endoscope (TED) is designed to help prevent serious
      complications in dilatational tracheotomies and facilitate their management. The
      endoscope has been specifically adapted to meet the require-ments of percutaneous
      dilatational tracheotomies. It is fully compatible with all current techniques of
      PDT. The method is easy to learn. The percutaneous dilatational tracheotomy with
      the Tracheotomy Endoscope is a seven-step procedure: Advantages of the
      Tracheotomy Endoscope: Injuries to the posterior tracheal wall ar impossible
      (tracheoesophageal fistulas, pneumothorax). Minor bleeding sites on the tracheal
      mucosa can be controlled with a specially curved suction-coagulation tube
      introudeced through the Tracheotomy Endoscope. In cases with heavy bleeding and a
      risk of aspiration, the rigid indwelling Tracheotomy Endoscope provides a secure
      route for reintubating the patient with a cuffed endotracheal tube. It also
      allows for rapid conversion to an open surgical procedure if necessary. All the
      parts are easy to clean and are autoclavable. This type of endoscopically guided
      PDT creates an optimal link between the specialties of intensive care medicine
      and otorhinolaryngology. The Tracheotomy Endoscope (TED) increases the standard
      of safety in PDT.

PMID- 16952076
TI  - [Endonasal Resection of Sinunasal Inverted Papilloma: "faux-pas" or "dernier
      crie"].

PMID- 16952077
TI  - [Dysphagia caused by neurogenic deglutition disorders and diffuse idiopathic
      skeletal hyperostosis (DISH)].
AB  - BACKGROUND: Diffuse idiopathic skeletal hyperostosis (DISH) may lead to dysphagia
      caused by osteophytes of the cervical spine. Osteophytes can be resected
      transorally or transcervically, but operative ablation should not be indicated
      generously because of the threat of severe complications. PATIENT: A fifty-year
      old man with dysphagia and loss of weight of 15 kg in the last three months is
      presented. He also suffered from a brain damage during infancy which caused grand
      mal-seizures. One seizure lead to cardiac arrest which required cardio-pulmonary
      resuscitation and subsequent tracheostomy. A spheric tumor of the posterior
      pharyngeal wall could be seen endoscopically, it appeared radiologically as an
      osteophytic formation of the segments C (3) - C (5). Ossification of the anterior
      longitudinal ligament was also seen. Diagnosis of DISH was made on the basis of
      these results. Contrast imaging of the esophagus and videofluoroscopy showed
      aspiration in terms of neurogenic disorders. The patient received a percutaneous
      gastrostomy after his case was discussed with neurologic and orthopaedic
      colleagues, because a causal therapy of the combined disease seemed to be
      impossible. CONCLUSION: Dysphagia in the presented case was caused by a
      combination of neurogenic deglutition disorders and oropharyngeal obstruction
      through osteophytes. Surgical removal of the osteophytes was not indicated
      because it would have put the patient at a certain risk, but only a part of the
      underlying problem would have been removed. Symptomatic therapy with a
      gastrostomy secures normocaloric diet. The patient's weight remained stable and
      he can follow his habitual daily routine.

PMID- 16952078
TI  - [Persistant chronic rhinosinusitis after endonasal sinus surgery].
AB  - Reasons for recurrent or persistent chronic rhinosinusitis could be the operation
      technique of the primary surgery, postoperative scarring, persistent inflammation
      or pathophysiologic agent or local factors. The management should be
      individualized and demands precise analysis of the clinical problem of the
      patient, nasal endoscopy and CT examination. Dependent on the results
      conservative or surgical therapy is mandatory. Medical and operative approaches
      are discussed in detail.

PMID- 16952079
TI  - [Chronic craniocervical acceleration injury (chronic KZBT). Therapeutic
      strategies from the view of a psychiatrist].

PMID- 16952082
TI  - [Surgical orthopedics in the framework of a humanitarian operation in the
      developing nation of Tanzania].

PMID- 16952086
TI  - Regional nerve block of the upper eyelid in oculoplastic surgery.
AB  - PURPOSE: To establish the efficacy of a regional nerve block of the upper eyelid
      and its effect on levator motor function. METHODS: Forty-one patients underwent
      surgery on 54 upper eyelids by one surgeon, after administration of a regional
      nerve block at the supraorbital notch. The amount of pain experienced by patients
      due to the local anesthetic injection and surgery was determined by using visual
      analogue scores. The effect of the local anesthetic injection on levator function
      was determined by comparing the measured levator function prior to and following
      administration. Any complications attributable to the regional sensory nerve
      block were recorded. RESULTS: Ninety-two percent of patients found the injection
      painless, and the rest reported negligible pain. The mean pain score for the
      injection was 2 (SD 1.3, range 0-6). The mean pain score for the surgery was 0.3
      (SD 0.6, range 0-3). No significant difference was found in levator function
      prior to and following the injection (pre-function: 14.4 mm, post-function: 13.4
      mm, p=0.01). One patient had hematoma formation at the site of injection.
      CONCLUSIONS: A regional nerve block of the upper eyelid achieves effective
      sensory anesthesia,without compromising motor function. This helps in an accurate
      assessment of intraoperative height during upper lid surgery.

PMID- 16952087
TI  - Endoscopically assisted balloon dacryocystoplasty and silicone intubation versus
      silicone intubation alone in adults.
AB  - PURPOSE: To compare the success rate of endoscopically assisted balloon
      dacryocystoplasty (DCP) and silicone intubation (DCP-SI) with endoscopically
      assisted silicone intubation alone (SI) in adults with incomplete nasolacrimal
      duct (NLD) obstruction. METHODS. In a retrospective nonrandomized comparative
      case series, 62 eyes of 55 adult patients with incomplete NLD obstruction
      underwent endoscopic probing and either SI (n=39 eyes) or DCP-SI (n=23 eyes)
      under general anesthesia. The last follow-up examination included diagnostic
      probing and irrigation if there was not success. Success was defined as
      disappearance of the symptoms and failure as partial improvement or absence of
      improvement at last follow-up. RESULTS: Patients ranged from 20 to 85 years of
      age (mean: 60.93, SD: 15.60). Tubes were removed between 6 and 20 weeks (mean:
      7.49, SD: 2.25) postoperatively. Follow-up ranged from 6 to 63 months (mean:
      14.60, SD: 10.33). Success rate of the eyes with SI (21/39, 53.84%) and DCP-SI
      (14/23, 60.86%) were not statistically different (p=0.60). Complications included
      slight nasal and canalicular bleeding in almost all eyes in both groups which was
      easily controlled, slit punctum in four eyes with bicanalicular intubation (4/50,
      8%), and monocanalicular tube lost in three eyes prematurely. CONCLUSIONS:
      Success rate of endoscopic DCP-SI had no statistically significant difference
      from silicone intubation alone in treatment of incomplete NLD obstruction in
      adults.

PMID- 16952088
TI  - Inferior turbinate fracture and congenital nasolacrimal duct obstruction.
AB  - PURPOSE: To evaluate the success rate of probing combined with inferior turbinate
      fracture in comparison with simple probing as a first attempt in the treatment of
      congenital nasolacrimal duct obstruction in children. METHODS: In a prospective
      interventional case-control study, 86 eyes from 61 children older than 6 months
      with congenital nasolacrimal duct obstruction underwent surgical intervention.
      Forty-two eyes of 33 patients underwent probing combined with infracturing of the
      inferior turbinate and 44 eyes of 28 patients underwent simple probing. The
      outcome evaluation included a standard ophthalmologic examination plus a dye
      disappearance test 2 months after the surgical intervention. RESULTS: In the case
      group (probing + infracture of the inferior turbinate), the results were good in
      22 (66.7%) patients, fair in 8 (24.2%), and poor in 3 (9.1%). In the control
      group (simple probing), the results were good in 20 (71.4%) patients, fair in 3
      (10.7%), and poor in 5 (17.9%) (p=0.9). Success rates were 91% and 82% in the
      case and control groups, respectively (p=0.4). CONCLUSIONS: Based on the results
      of this study, infracturing of the inferior turbinate does not increase the
      success rate of simple probing as a first attempt.

PMID- 16952089
TI  - A regression model for correcting intraocular lens power after refractive surgery
      independent of preoperative data.
AB  - PURPOSE: To find a method of calculating intraocular lens (IOL) power that may be
      independent of preoperative data in eyes that have previously undergone myopic
      laser in situ keratomileusis (LASIK). METHODS: In 148 eyes of 75 patients, before
      and 6 months after LASIK, IOL power was calculated with SRK/T formula utilizing
      the spherical equivalent as the desired target refraction. Assuming that LASIK
      does not alter the crystalline lens refractive properties, IOL calculation error
      (CER) was estimated with this formula: CER = [pre-LASIK IOL power]/[post-LASIK
      IOL power]. Then the authors used postoperative biometry and Orbscan II corneal
      topography data in multiple regression models to find the best variables to
      predict the CER. Predicted amount of error which is calculated independent of
      preoperative data could be used to correct the post-LASIK calculated IOL:
      [corrected post-LASIK IOL power] = CER x [post-LASIK IOL power]. RESULTS: A
      regression model with these predictors was found: axial length in millimeters
      (L), radius of the anterior corneal surface best fitted sphere in millimeters
      divided by radius of the posterior corneal surface best fitted sphere in
      millimeters (AntBFS/PostBFS), corneal central 5 millimeters mean power in
      diopters divided by corneal central 3 millimeters mean power in diopters (mean 5
      mm/mean 3 mm), the post-LASIK IOL power, and the post-LASIK simulated K reading.
      The model R square was 0.88. CONCLUSIONS: There is correlation between post-LASIK
      biometry values and IOL power correction factor. This study presents a new model
      for further investigation.

PMID- 16952090
TI  - Conservative treatment of keratoconus by riboflavin-uva-induced cross-linking of
      corneal collagen: qualitative investigation.
AB  - PURPOSE: To assess corneal tissue modifications after riboflavin-UVA-induced
      cross-linking of corneal collagen in patients with progressive keratoconus as
      well as regeneration of epithelium and subepithelial nerve plexus by in vivo HRT
      II system confocal microscopy in humans. METHODS: Ten patients with progressive
      keratoconus were treated by riboflavin-UVA-induced cross-linking of corneal
      collagen, involving assessment of ultrastructural modifications of the corneal
      epithelium and subepithelial nerve plexus by HRT II system confocal microscopy.
      Treatment included instillation of 0.1% riboflavin-20% dextrane solution 5
      minutes before UVA irradiation and every 5 minutes for a total of 30 minutes.
      Radiant energy was 3 mW/cm 2 or 5.4 Joule/cm 2 and the source was dual UVA (370
      nm) light-emitting LED. The protocol included the operation followed by
      antibiotic medication and eye dressing with a soft therapeutic contact lens.
      Changes in epithelium and subepithelial and stromal nerve plexus were assessed by
      HRT II system confocal microscopy in vivo. RESULTS: After 5 days of soft contact
      lens wearing, corneal epithelium has a regular morphology and density.
      Disappearance of subepithelial stromal nerve fibers was observed in the central
      irradiated area where, 1 month after the operation, initial reinnervation was
      microscopically observed. No changes in nerve fibers were observed in the
      peripheral untreated with a clear lateral transition between the two areas. Six
      months after the operation, the anterior subepithelial stroma was recolonized by
      nerve fibers with restoration of corneal sensitivity. CONCLUSIONS: HRT II system
      confocal microscopy confirms corneal epithelium restore and re-innervation after
      riboflavin-UVA-induced collagen cross-linking directly in vivo in humans.

PMID- 16952091
TI  - Corneal topographic changes after scleral buckling.
AB  - PURPOSE: To evaluate corneal topographic changes and induced corneal astigmatism
      after scleral buckling (SB). METHODS: This interventional case series includes
      all patients who had undergone scleral buckling for rhegmatogenous retinal
      detachment (RRD) during a 1-year period. Patients were divided into four groups
      according to type and extent of scleral buckling which depended on the discretion
      of a retina specialist. Videokeratography was performed for all patients
      preoperatively and repeated 1 and 3 months after SB. RESULTS: Thirty-nine eyes of
      39 patients (29 male, 74.7%) with mean age of 50.35+/-20 years (range 13-80) were
      finally analyzed. There was no statistically significant difference among the
      groups in terms of preoperative corneal astigmatism, surface regularity index
      (SRI), surface asymmetry index (SAI), mean keratometry (mean K), and potential
      visual acuity (PVA ). Overall, preoperative mean K was 43.97+/-1.78 D, which
      reached 44.2+/-2.02 D and 43.92+/-2.16 D 1 and 3 months after the operation. Mean
      preoperative SRI was 0.58+/-0.4, which increased to 1.24+/-1.18 and 1.29+/-1.13 1
      and 3 months after the operation respectively. Mean preoperative SAI was 0.39+/
      0.21, which increased to 0.73+/-0.37 and 0.75+/-0.66 1 and 3 months after the
      procedure. Changes in SAI at 1 and 3 months following SB were significant (p
      values <0.001); however, these postoperative values were not significantly
      different. Mean preoperative PVA was 0.07+/-0.75 logMAR (equivalent to 20/20) but
      decreased to 0.24+/-0.25 (equivalent to 20/30) and 0.27+/-0.29 (equivalent to
      20/40) 1 and 3 months after SB, respectively. CONCLUSIONS: Significant changes in
      corneal topographic indices including increases in SRI and SAI and a concomitant
      decrease in PVA may occur after SB procedures. These induced changes must be
      considered and appropriately addressed postoperatively to provide the best
      possible corrected vision.

PMID- 16952092
TI  - Homocysteine levels in plasma and sensorineural hearing loss in patients with
      pseudoexfoliation syndrome.
AB  - PURPOSE: To determine the incidence and severity of hearing loss in different
      frequencies in patients with pseudoexfoliation. Furthermore, possible links
      between homocysteine and pseudoexfoliation were evaluated. METHODS: Seventy-five
      consecutive patients with pseudoexfoliation and 75 sex- and age-matched subjects
      without pseudoexfoliation as control group were included in this prospective case
      control study. Pure-tone audiometry was obtained in all subjects in both groups.
      Blood samples were obtained from 70 patients with pseudoexfoliation after
      overnight fasting for levels of homocysteine and analyzed by routine laboratory
      measurements. RESULTS: Fifty-two (69%) patients with pseudoexfoliation and 39
      (52%) controls had sensorineural hearing loss in speech frequencies. The
      difference between pseudoexfoliation and control group with regard to the
      frequency of sensorineural hearing loss in speech frequencies was statistically
      significant (p=0.03). No relationship was found between the degree of
      glaucomatous damage and hearing threshold variables in the patients with
      pseudoexfoliation glaucoma. Plasma homocysteine levels showed no significant
      difference when patients with pseudoexfoliation and hearing loss were compared
      with patients with pseudoexfoliation and normal hearing threshold (p=0.5).
      Hyperhomocysteinemia was found in 58% (29/50) of pseudoexfoliation patients with
      hearing loss, and 55 % (11/20) of pseudoexfoliation patients with normal hearing
      threshold (p=0.8). No statistically significant correlation was found between
      plasma homocysteine and hearing loss in patients with pseudoexfoliation.
      CONCLUSIONS: These findings suggest an association between sensorineural hearing
      loss and pseudoexfoliation in patients with pseudoexfoliation and glaucoma. The
      severity of hearing loss was not correlated with the degree of glaucomatous
      damage. There is no association between increased homocysteine levels and hearing
      loss in patients with pseudoexfoliation.

PMID- 16952093
TI  - Levels of zinc, iron, and copper in patients with pseudoexfoliative cataract.
AB  - PURPOSE: To investigate the aqueous humor, lens, and serum concentrations of
      zinc, iron, and copper in patients with pseudoexfoliative cataract and compare
      with patients who have senile cataract without pseudoexfoliation. METHODS: Twenty
      five patients with pseudoexfoliative cataract and 25 patients with senile
      cataract as control group were enrolled in the study. Samples from aqueous humor,
      serum, and lens materials during extracapsular cataract extraction (ECCE) were
      collected from all patients. The levels of selected trace elements in three
      samples in all groups were assayed with atomic absorption spectrometry (AAS) and
      statistical analyses were performed with t-test for independent samples except
      lens zinc and serum copper levels. The data weren't normally distributed,
      therefore Mann-Whitney U test applied for these parameters. RESULTS: The zinc and
      copper levels in aqueous humor of PEX group were significantly higher than those
      of control group (p<0.001). The iron levels in aqueous humor were not
      significantly different in PEX group and control group (p=0.252). The copper
      content of lenses was significantly increased in PEX group compared to control
      group (p=0.029). The iron and zinc content of lenses had no significant
      differences between the two groups (p=0.248, p=0.719, respectively). The levels
      of iron and copper in serum were significantly increased in PEX group compared to
      control group (p<0.001 and p<0.002, respectively). The zinc level in serum had no
      significant differences between the two groups (p=0.823, p=0.472, respectively).
      CONCLUSIONS: Zinc, iron, and especially copper may play a role in PEX syndrome.

PMID- 16952094
TI  - First day review after uncomplicated phacoemulsification: is it necessary?
AB  - PURPOSE: To determine whether first day follow-up is necessary after routine
      uncomplicated phacoemulsification cataract surgery. METHODS: Data collected
      prospectively at day 1 postoperative review. RESULTS: In 510 consecutive cases,
      serious complications occurred in 8 (1.6%) (wound leak [4], corneal abrasion [2],
      iris prolapse [1], hyphema [1]). Intraocular pressure (IOP) >30 mmHg was found in
      26 (5.1%) and was strongly associated with a diagnosis of pre-existing glaucoma
      or ocular hypertension (odds ratio [OR] 7.7). Symptoms of headache or ocular
      discomfort occurred in 40 (7.8%), mostly in association with raised IOP, and were
      also associated with pre-existing glaucoma or ocular hypertension (OR 4.7).
      Central corneal edema was found in 61 (12.0%). In the absence of corneal edema,
      IOP was >30 mmHg in only two cases (0.39%). CONCLUSIONS: Few sight-threatening
      complications were detected on the morning after an uncomplicated procedure.
      First day follow-up may be safely omitted if adequate patient counseling is
      undertaken and there is provision of adequate access to eye services. Review
      prior to discharge on the day of surgery would provide an opportunity to detect
      these few surgical complications and for counseling. A diagnosis of glaucoma or
      ocular hypertension is a risk factor for significantly raised next day IOP and
      these patients are more likely to experience postoperative discomfort. They may
      benefit from prophylactic treatment.

PMID- 16952095
TI  - Blood pressure effects on retinal vessel diameter and flicker response: a 1.5
      year follow-up.
AB  - PURPOSE: The study examined the influence of individual blood pressure changes
      overtime on retinal vessel diameter and the latter's response to flicker light.
      METHODS: The diameter of a retinal arterial and venous segment was measured
      continuously on-line with a Dynamic Vessel Analyzer in 20 patients twice (mean
      interval between examinations of 24 months). Eleven patients had no
      cardiovascular disease. Nine patients had arterial hypertension and were
      untreated at the time of the first measurement; at the time of the second
      measurement they were undergoing various antihypertensive therapies. Each test
      consisted of a 50-s baseline plus three 20-s periods of flicker stimulation
      followed by an 80-s period of observation. During the examinations the blood
      pressure was measured at 1-minute intervals. RESULTS: In the hypertension group
      changes in the mean arterial blood pressure (MAP) correlated significantly with
      changes in the arterial baseline diameter (y = -0.1 - 0.37x, r =0.74, p
      (increase) <0.03). A comparison of the two measurements showed no such
      relationship in the group of cardiovascularly healthy subjects. The venous
      baseline and the arterial and venous flicker response did not change
      significantly in either group between the two measurements and showed no
      relationship to blood pressure changes. CONCLUSIONS: In hypertensive subjects,
      long-term therapy-related changes in blood pressure induced a change in the
      arterial baseline by approximately +3.7 microm/-10 mmHg MAP. An influence of
      lowering MAP to the arterial flicker response could not be detected.

PMID- 16952096
TI  - Follow-up after intravitreal triamcinolone acetonide for diabetic macular edema.
AB  - PURPOSE: To report on the follow-up of patients who received an intravitreal high
      dosage injection of triamcinolone acetonide (IVTA) as treatment of diffuse
      diabetic macular edema. METHODS: The clinical interventional case-series study
      included 109 eyes (90 patients) with diffuse diabetic macular edema who
      consecutively received an IVTA of about 20 mg. Mean follow-up was 11.2 +/- 6.2
      months. RESULTS: Visual acuity improved significantly (p<0.001) from 0.89 +/-
      0.33 logMAR to a best minimum of 0.65 +/- 0.35 logMAR. An increase in best visual
      acuity by at least 1 Snellen line, 2 lines, and 3 lines was found in 91 (83%)
      eyes, 68 (62%) eyes, and 45 (41%) eyes, respectively. Differences in visual
      acuity between baseline and follow-up examinations were significant for
      measurements performed at 1 month (p<0.001), 2 months (p<0.001), 3 months
      (p<0.001), and at 6 months (p=0.001) after the injection. At 9 months after the
      injection, mean visual acuity regressed significantly so that visual acuity at 9
      months (p=0.83) and at 12 months after the injection (p=0.58) compared with
      baseline values did not differ significantly. Forty-seven (43%) eyes developed a
      rise in intraocular pressure (pressure >21 mmHg) for 6 to 8 months after the
      injection. No other severe complications were detected. CONCLUSIONS: The duration
      of a visual acuity increase and intraocular pressure rise after high-dosage IVTA
      in diffuse diabetic macular edema is about 6 to 8 months. Compared with data in
      the literature, the high-dosage IVTA may not have a markedly higher profile of
      side effects than low-dosage IVTA.

PMID- 16952097
TI  - Pars plana vitrectomy and removal of the internal limiting membrane in diabetic
      macular edema unresponsive to grid laser photocoagulation.
AB  - PURPOSE: To evaluate the effectiveness of pars plana vitrectomy (PPV) with
      removal of the internal limiting membrane (ILM) in diabetic patients with macular
      edema unresponsive to grid laser photocoagulation. METHODS: In this randomized
      controlled study, 20 eyes of 10 patients with diabetic macular edema unresponsive
      to grid laser photocoagulation were evaluated. PPV with ILM removal was performed
      randomly in one eye each of 10 patients and taken as the study group; the
      untreated fellow eyes were taken as the control group. Main outcome measures were
      foveal thickness changes measured with optical coherence tomography and
      preoperative and post-operative visual acuity. Mann-Whitney U, Wilcoxon, and chi
      square tests were used in statistical analysis. RESULTS: The mean age of the
      patients was 61.5+/-6 years (range 51 to 71). All patients were followed up for
      12 months. In the study group, mean foveal thickness was 391.3+/-91.6 microm
      preoperatively and 225.5+/-49.4 microm postoperatively (p=0.009). In the control
      group, mean foveal thickness was 356.2+/-140 microm at baseline and 318.4+/-111.1
      microm at 12-month follow-up (p=0.138). Mean decrease in foveal thickness was
      165.8+/-114.8 microm in the study group and 37.8+/-71.2 microm in the control
      group (p=0.016). In the study group, best-corrected log-MAR visual acuity was
      0.71+/-0.43 preoperatively and 0.54+/-0.45 postoperatively (p=0.125). In the
      control group, best-corrected logMAR visual acuity was 0.43+/-0.44 at baseline
      and 0.59+/-0.55 at 12-month follow-up (p=0.235). In the study group, visual
      acuity improved by two or more lines in 4 eyes (40%) and remained stable in 6
      eyes (60%). In the control group, visual acuity improved by two or more lines in
      1 eye (10%) and decreased by two or more lines in 3 eyes (30%). CONCLUSIONS: PPV
      with ILM removal appears to be an effective procedure for reducing diabetic
      macular edema unresponsive to grid laser photocoagulation. A further study with a
      large number of patients is required to assess the effectiveness and safety of
      this procedure.

PMID- 16952098
TI  - Toxic keratolysis from combined use of nonsteroid anti-inflammatory drugs and
      topical steroids following vitreoretinal surgery.
AB  - PURPOSE: To evaluate the corneal complications associated with the combined use
      of non-steroid anti-inflammatory drugs (NSAIDs) and topical steroids following
      vitreoretinal surgery. METHOD: Description of corneal lesions in three patients
      after vitrectomy with use of topical ketorolac and prednisolone acetate. RESULTS:
      Three eyes of three patients developed an atrophic central corneal ulcer with
      stromal thinning following a pars plana vitrectomy under local anesthesia.
      Lesions were asymptomatic and were found during a routine examination 2, 3, and 8
      weeks after surgery, respectively. Surgical indications were as follows: a
      preretinal membrane, choroidal neovascularization, and massive uveal effusion
      following cataract surgery. Topical postoperative treatment was as follows:
      ketorolac 4 times a day, a combination of prednisolone acetate, polymyxin B, and
      neomycin 6 times a day, and 1% cyclopentolate 3 times a day. Suspension of
      ketorolac and ocular occlusion led to the resolution of corneal lesions between
      2.5 and 3 months later, yielding a central superficial scarring, which showed no
      changes after a follow-up of 3 years. CONCLUSIONS: Toxic keratolysis may appear
      as a secondary effect of the combined use of topical NSAIDs and steroids
      following vitreo retinal surgery and must be taken into account in the
      differential diagnosis of postoperative corneal lesions.

PMID- 16952099
TI  - The diagnostic yield of vitrectomy specimen analysis in chronic idiopathic
      endogenous uveitis.
AB  - PURPOSE: The low diagnostic yield of vitrectomy specimen analysis in chronic
      idiopathic uveitis (CIU) has been related to the complex nature of the underlying
      disease and to methodologic and tissue immanent factors in older studies. In an
      attempt to evaluate the impact of recently acquired analytic methods, the authors
      assessed the current diagnostic yield in CIU. METHODS: Retrospective analysis of
      consecutive vitrectomy specimens from patients with chronic endogenous uveitis (n
      = 56) in whom extensive systemic workup had not revealed a specific diagnosis
      (idiopathic) and medical treatment had not resulted in a satisfying clinical
      situation. Patients with acute postoperative endophthalmitis served a basis for
      methodologic comparison (Group 2; n = 21). RESULTS: In CIU, a specific diagnosis
      provided in 17.9% and a specific diagnosis excluded in 21.4%. In 60.7% the
      laboratory investigations were inconclusive. In postoperative endophthalmitis,
      microbiological culture established the infectious agent in 47.6%. In six of
      eight randomly selected cases, eubacterial PCR identified bacterial DNA
      confirming the culture results in three, remaining negative in two with a
      positive culture and being positive in three no growth specimens. A double
      negative result never occurred, suggesting a very high detection rate, when both
      tests were applied. CONCLUSIONS: The diagnostic yield of vitrectomy specimen
      analysis has not been improved by currently routinely applied methods in recent
      years in contrast to the significantly improved sensitivity of combined
      standardized culture and PCR analysis in endophthalmitis. Consequently, the low
      diagnostic yield in CIU has to be attributed to insufficient understanding of the
      underlying pathophysiologic mechanisms.

PMID- 16952100
TI  - A pilot study of the use of objective structural clinical examinations for the
      assessment of ophthalmology education.
AB  - PURPOSE: A pilot study was carried out to evaluate the practicality, reliability,
      and validity of an objective structured clinical examination (OSCE) for assessing
      the clinical skills and abilities of specialists in ophthalmology. METHODS: Ten
      unfolded OSCE style, criterion referenced questions were asked to nine candidates
      to assess their clinical skills and abilities, as opposed to subject knowledge.
      Candidate and assessor reactions to the examination process were monitored and
      analyzed using participant observation and questionnaires administered
      immediately after the event. Relevant statistical techniques were applied to the
      results. RESULTS: A total of 89% of candidates passed the examination, with the
      pass boundary set at 70%. Candidates revealed themselves more successful in
      meeting clinical skill criteria (mean 77%) than clinical ability criteria (mean
      72%). Candidates, assessors, and observers all expressed the view that the OSCE
      pilot had been a successful way of assessing clinical skills and abilities.
      CONCLUSIONS: OSCE style assessment is an effective and efficient means of
      assessing skills and abilities in clinical ophthalmology education.

PMID- 16952101
TI  - Causes of blindness in Southwestern Nigeria: a general hospital clinic study.
AB  - PURPOSE: This hospital-based study was carried out to assess the common causes of
      blindness in Ibadan, the largest city in the southwestern part of Nigeria, and to
      strengthen the primary eye care approach to control and reduction of cases of
      blindness in the community. METHODS: Following Hospital Ethical Board approval
      and informed consent of participants, a prospective study was performed in which
      1,544 consecutive patients with bilateral or unilateral blindness seen between
      January and December 2003 at the Ring Road State Hospital, Ibadan, Nigeria, were
      evaluated for causes of blindness. Visual acuity was measured with an illuminated
      Snellen chart placed 6 meters away from the participants. This was followed by
      pen torch examination and dilated funduscopy with a direct ophthalmoscope.
      Friedman field analyzer was used to measure visual field. Patients with corrected
      visual acuity of less than 3/60 in the better eye or with visual field of less
      than 10 degrees from fixation were considered blind according to the World Health
      Organization criteria. RESULTS: The 1,544 patients had a mean age of 53.5 years
      (range, 4 to 96 years); 858 (56%) were male and 686 (44%) were female. Blindness
      was bilateral in 471 (30%) patients and unilateral in 1,073 (70%). When those
      persons with unilateral and bilateral blindness were grouped together,
      individuals within the 60 to 79 years age bracket were 667 (44%) and constituted
      the largest group of all blind persons. The leading causes of bilateral blindness
      were cataract, 171 (36%); glaucoma, 138 (29%); and optic atrophy, 21 (4%). The
      most common causes of unilateral blindness were cataract, 446 (41%); glaucoma,
      213 (20%); and those referable to trauma, 116 (11%). CONCLUSIONS: Cataract and
      glaucoma are the main causes of bilateral and uniocular blindness in the study
      area.

PMID- 16952102
TI  - Sarcomatoid carcinoma and orbital apex syndrome.
AB  - PURPOSE: To report a case of sarcomatoid carcinoma and orbital apex syndrome in a
      previously healthy adult. METHODS: A previously healthy 45-year-old man presented
      with exophthalmos of the left eye and a mass visible through his left nostril. A
      biopsy was performed and immunohistochemistry was used to confirm the diagnosis
      of the tumor. The patient was treated with chemotherapy and radiotherapy.
      RESULTS: After treatment, we observed a substantial reduction in the size of the
      mass, but side effects of treatment developed. The visual acuity of the left eye
      was no light perception. Eight months later, the patient presented with bone and
      liver metastases, and he died 4 months later. CONCLUSIONS: Sarcomatoid carcinoma
      is an aggressive tumor that can produce compressive symptoms with very poor
      visual and survival prognoses. A cranio-orbital computed tomography scan should
      be performed when patients present with symptoms of conjunctivitis and orbital
      apex syndrome.

PMID- 16952103
TI  - Late leakage of filtering bleb in a patient with orbital pseudotumor.
AB  - PURPOSE: To report an unusual case of spontaneous late leakage of filtering bleb
      in a patient with orbital pseudotumor. METHODS: Single case report. RESULTS: A 53
      year-old woman developed spontaneous leakage of bleb in her right eye 23 years
      after trabeculectomy with application of mitomycin-C (MMC). Two weeks later, her
      symptoms were blurring of vision, increasing redness, and dull ocular pain in the
      right eye. The inflammatory signs were suggestive of endophthalmitis, orbital
      cellulites, or pseudo-tumor. Absence of ophthalmoplegia, fever, and raised white
      cell count, together with the computed tomographic scan finding, confirmed the
      diagnosis of orbital pseudotumor. She responded well to oral steroids.
      CONCLUSIONS: Orbital pseudotumor may initially present with spontaneous late
      leakage in a bleb augmented by MMC. Orbital pseudotumor should be added to the
      list of differential diagnoses when facing a patient with an inflamed, chemotic,
      proptotic eye in the presence of a late bleb leak.

PMID- 16952104
TI  - Bilateral atypical nodular posterior scleritis.
AB  - PURPOSE: To evaluate ocular features of nodular posterior scleritis simulating
      choroidal melanoma. METHODS: A 60-year old woman presented with blurred vision in
      her right eye of two weeks duration. On examination she had a mild right-globe
      proptosis with an episcleral nodular mass as well as a large elevated
      nonpigmented choroidal mass involving the nasal quadrant. RESULTS: A and B-scan
      ultrasonography showed a medium to high-reflective solid choroidal mass. MRI
      demonstrated a bi-convex mass in the medial aspect of the right globe with signal
      characteristics compatible with choroidal melanoma. Biopsy of the extraocular
      lesion demonstrated chronic inflammatory cell infiltrate suggestive of posterior
      scleritis. She responded to corticosteroid therapy. On evaluation 41 months later
      she was noted to have a similar choroidal mass in the left eye. CONCLUSIONS: The
      physician should be aware of the clinical manifestations and diagnostic hall
      marks of nodular posterior scleritis in order to differentiate this inflammatory
      process from choroidal melanoma.

PMID- 16952105
TI  - Band keratopathy: a modified treatment.
AB  - PURPOSE: The surgical treatment of band keratopathy usually consists of abrasion
      of the corneal epithelium followed by removal of the subepithelial calcium
      deposits by means of an ethylenediamine-tetraacetic acid (EDTA) solution. In
      order to reduce the discomfort and pain that occur after corneal abrasion, the
      authors developed a modified technique that avoids the abrasion of the
      epithelium. METHODS: In three patients (four eyes) with long-standing band
      keratopathy, the epithelium was detached with a 19% ethanol solution and placed
      gently toward the limbus, a method also used in laser-assisted subepithelial
      keratectomy (LASEK). After clearing the anterior stroma with EDTA solution, the
      epithelial flap is unrolled and a bandage contact lens applied. RESULTS:
      Postoperative pain was greatly reduced and after removal of the contact lens no
      pain was reported. CONCLUSIONS: This modified epithelium-sparing treatment of
      band keratopathy shows good results while reducing postoperative pain.

PMID- 16952106
TI  - Molluscum contagiosum in a patient with no risk factors.
AB  - PURPOSE: To report a case of molluscum contagiosum in a patient with no risk
      factors. METHODS: A 38-year-old patient with a tumor located in the lower eyelid
      that appeared 5 months previously was seen in the authors' hospital. The lesion
      had grown slowly and appeared as a crateriform mass with elevated edges. It was
      surgically excised and the histopathology study confirmed the diagnosis of
      molluscum contagiosum. Risk factors were absent. RESULTS: The histopathologic
      study confirms the presence of eosinophilic inclusion bodies in the keratinocytes
      cytoplasm. CONCLUSIONS: External evaluation of the lower lid lesion did not show
      the morphologic configuration of a molluscum contagiosum. A virus can be
      suspected if attention is paid to the margin of the eyelid and the patient's age.

PMID- 16952107
TI  - Bilateral cataract following lightning injury.
AB  - PURPOSE: To report a case of bilateral cataract with posterior vitreous
      detachment induced by lightning injury. METHODS: A case report of 30 year old man
      injured by lightning. RESULTS: The patient developed visually significant
      bilateral cataract after four years of the initial insult on the scalp. The exit
      wound was noted on the right foot. Fundus evaluation after cataract extraction
      revealed posterior vitreous detachment. CONCLUSIONS: Lightning can induce various
      ocular complications. Decrease in vision due to cataract is usually seen years
      after the initial lightning injury as the initial changes are in the mid
      periphery and often missed in the acute setting. Posterior vitreous detachment
      induced by lightning can rarely lead to retinal tear formation and subsequently
      retinal detachment. The severity of entry and exit may not give a true picture of
      the internal organ damage.

PMID- 16952108
TI  - Allergic contact dermatitis caused by latanoprost ophthalmic solution.
AB  - PURPOSE: Latanoprost is a prostaglandin F2 alfa analog that lowers intraocular
      pressure by increasing uveoscleral outflow. Herein we describe two cases of
      allergic contact dermatitis (ACD) to latanoprost. METHODS: A 69-year-old man with
      open-angle glaucoma developed erythematous erosive swelling of bilateral eyelids
      after 4 months of latanoprost therapy. An 84-year-old man with open-angle
      glaucoma had pruritic erythematous plaques on the bilateral lower eyelids after
      latanoprost therapy for 4 months. RESULTS: In both cases, latanoprost was
      discontinued and the condition gradually resolved in 1 month. The eyelid lesions
      recurred in days upon latanoprost rechallenge, but subsided after cessation of
      rechallenge. CONCLUSIONS: ACD should be suspected if patients on latanoprost
      therapy have pruritus, erythema, swelling, or erosions on the eyelids even when
      the symptoms appear after several months of therapy, especially in the elderly.

PMID- 16952109
TI  - Adenoma of the nonpigmented ciliary epithelium.
AB  - PURPOSE: To report the clinicopathologic features of an adenoma of the
      nonpigmented ciliary epithelium. DESIGN: Single interventional case report.
      METHODS. A nonpigmented iris and ciliary body tumor was diagnosed in a 66-year
      old woman who complained of blurred vision related to a unilateral cataract. A
      combined cataract surgery and partial lamellar sclerouvectomy was performed.
      RESULTS: Histopathologic findings disclosed an adenoma of the nonpigmented
      ciliary epithelium. CONCLUSIONS: Unilateral cataract in an adult patient can be
      rarely related to a tumor growing from the ciliary epithelium. Adenoma of the non
      pigmented ciliary epithelium may mimic an amelanotic melanoma. Partial lamellar
      sclerouvectomy is an effective method to manage this condition and to confirm the
      diagnosis.

PMID- 16952110
TI  - Microperimetric evaluation of macula in retinopathy of membranoproliferative
      glomerulonephritis type II: a case report.
AB  - PURPOSE: To report on the microperimetric evaluation of the central visual field
      in a patient with retinopathy due to membranoproliferative glomerulonephritis.
      METHODS: The central 20 degrees visual field was evaluated using fundus-related
      perimetry with (Nidek MP1) microperimeter in a patient with proven
      membranoproliferative glomerulonephritis type II, who had multiple drusen-like
      lesions involving the posterior pole of both eyes, with corresponding window
      defects on fundus fluorescein angiogram. RESULTS: Static threshold perimetry of
      the central 20 degrees using a 10 dB threshold, Goldmann size II stimulus, with
      (Nidek-MP1) microperimeter showed reduction in retinal sensitivity in the
      parafoveal and in the temporal paramacular areas in both the eyes that had drusen
      like lesions. CONCLUSIONS: Early loss of function in retinopathy of
      membranoproliferative glomerulonephritis type II can probably be detected by
      fundus-related microperimetry.

PMID- 16952111
TI  - Late effect of external eye irradiation on choroidal circulation.
AB  - PURPOSE: To report two cases of atypical late onset radiation chorioretinopathy
      occurring 15 and 25 years post exposure and the indocyanine green (ICG)
      angiographic findings in these patients. METHODS: Clinical examination and
      imaging including fluorescein and ICG angiography were performed. RESULT: Fundus
      examination of the first patient revealed microangiopathy with intraretinal
      hemorrhages, lipid exudation, telangiectatic and aneurysmal capillary changes.
      Indocyanine green angiography showed an apparent chorioretinal anastomosis and
      delayed perfusion of the choriocapillaris. Fundus examination of the second
      patient revealed a pigment epithelial detachment and retinal pigment epithelial
      changes. Indocyanine green angiography showed atypical, tortuous, dilated,
      choroidal vessels as well as areas of hypoperfusion. Both patients had multiple
      dot-like hyperfluorescent spots in the midphase of the ICG angiogram.
      CONCLUSIONS: External radiation exposure may lead to both retinal and choroidal
      alterations which may be independent events and which may manifest after a long
      period of quiescence. Furthermore, ICG angiography appears to be a useful
      diagnostic tool to study the alterations of the choroid following external eye
      irradiation.

PMID- 16952112
TI  - Retinal fibrovascular proliferation associated with Nocardia subretinal abscess.
AB  - PURPOSE: To report the development of extensive fibrovascular proliferation in
      association with Nocardia subretinal abscess. METHOD: Case report. RESULTS:
      Extensive retinal neovascularization with tractional retinal detachment developed
      soon after ocular involvement in a 61-year-old patient with systemic nocardiosis.
      Fundus fluorescein angiography showed extensive area of capillary nonperfusion
      and severe leakage from the neovascular complex. The Nocardia subretinal abscess
      responded to systemic antibiotics, and the retinal neovascularization and
      tractional retinal detachment stabilized after 3 months. CONCLUSIONS: Retinal
      ischemia and severe retinal neovascularization may complicate intraocular
      nocardiosis. The authors propose secondary retinal vasculitis as a contributing
      factor towards the development of retinal ischemia in this setting.

PMID- 16952113
TI  - A case of diabetic retinopathy with both retinal neovascularization and complete
      posterior vitreous detachment.
AB  - PURPOSE: Report of a case with retinal neovascularization developing in the
      setting of diabetic retinopathy despite complete posterior vitreous detachment
      (PVD). CASE REPORT: A 76-year-old man had had type II diabetes mellitus for more
      than 30 years. Weiss' ring was detected by direct and indirect ophthalmoscopy.
      PVD was thus considered to be complete. On the other hand, fluorescein
      angiography showed two areas of hyperfluorescence at the margin of the retinal
      nonperfusion area. CONCLUSIONS: The present case underscores the importance of
      periodic follow-up using fluorescein angiography, given the probability of
      retinal neovascularization development and proliferative changes for many years
      even in diabetic retinopathy associated with complete PVD.

PMID- 16952114
TI  - Necrotic uveal melanoma with orbital inflammation.
AB  - PURPOSE: Extraocular extension of uveal melanoma can be accompanied by proptosis
      and signs of orbital inflammation but this clinical presentation is an uncommon
      feature if the tumor is solely intraocular. METHODS: Case report. RESULTS: The
      authors describe a patient with a medium-sized necrotic uveal melanoma, without
      extraocular spread, presenting with the clinical picture of orbital cellulitis.
      CONCLUSIONS: The ophthalmologist needs to be aware of this uncommon presentation
      of uveal melanoma, and not assume the presence of proptosis and orbital
      inflammation as signs of extraocular extension.

PMID- 16952115
TI  - Progressive severe visual loss after long-term withdrawal from thioridazine
      treatment.
AB  - PURPOSE: To report advanced thioridazine-induced retinopathy in a 50-year-old
      woman with evidence of progressive severe loss of vision over 30 years after
      withdrawal from thioridazine treatment. METHODS: The ocular fundus examination
      revealed areas of retinal pigment epithelium (RPE) clumping as well as
      generalized atrophy of the RPE and choroid. The patient experienced visual loss
      to the level of no light perception in both eyes despite the fact that the
      funduscopic appearances of her optic nerves and retinal vasculature remained
      relatively normal. CONCLUSIONS: This case demonstrates that severe progressive
      visual loss can occur several years after the cessation of chronic thioridazine
      treatment.

PMID- 16952116
TI  - Ocular Munchausen syndrome resulting in bilateral blindness.
AB  - PURPOSE: Munchausen syndrome is a factitious disorder in which patients knowingly
      harm themselves for subconscious psychological reasons in order to be
      hospitalized. Recognition of this psychopathology is important, to prevent
      potentially severe eye damage. Ocular Munchausen syndrome is uncommon. The
      authors describe an elderly woman with recurrent, probably self-induced, ocular
      trauma leading to bilateral blindness. The authors are unaware of any previously
      reported cases of Munchausen syndrome resulting in bilateral blindness and
      occurring in old age. CASE REPORT: A 73-year-old woman was first seen in 1991
      with a closed-globe injury to the right eye, apparently following a household
      fall. Physical examination showed no sign of extraocular trauma. Right visual
      acuity was 20/30 after 2 months. She was readmitted in May 2003 with left globe
      rupture, allegedly following a domestic fall. No extraocular trauma was found.
      She developed ocular phthisis 6 months postoperatively. The patient was admitted
      again in February 2004 with right globe rupture, following another alleged
      domestic fall. Physical examination showed no sign of extraocular trauma. Right
      visual acuity was 20/400 2 months postoperatively. Psychiatric evaluation
      revealed Munchausen syndrome. Psychotherapy was prescribed, but refused by her
      family. CONCLUSIONS: Diagnosis of Munchausen syndrome is difficult to make in the
      ophthalmic department. Munchausen patients have little or no ability to control
      their self-destructive behavior. A sympathetic and supportive approach is
      therefore required and these patients should be urgently referred to a
      psychiatrist with experience in factitious disorders. Even with psychotherapy,
      which is often refused, the prognosis remains poor.

PMID- 16952118
TI  - Effect of architecture on the tensile properties of triblock copolymers in a
      lamellar phase.
AB  - We have used self-consistent field theory to calculate the tensile moduli of
      triblock copolymers in lamellar microstructures prepared from linear and star
      architectures. The extensional moduli K(33) are the main contributors to the
      tensile moduli, and the contribution of K(U)33 (the internal energy contribution
      to K(33)) is the main component of the value of K(33). We find that the tensile
      moduli of ABC three-miktoarm star terpolymers are smaller than those of ABC
      linear triblock copolymers having identical components, presumably for two main
      reasons. First, for the ABC three-miktoarm star terpolymers, the contributions of
      K(U)33 are larger than those of the linear triblock copolymers; we attribute this
      phenomenon to the star terpolymers having smaller lamellar domain sizes at
      equilibrium relative to those of the linear triblock copolymers. Second,
      conformational entropies play an important role in affecting the tensile moduli,
      mainly because of the different degrees of freedom of the various chains. In
      contrast, the shear moduli contribute negligibly to the tensile moduli.

PMID- 16952119
TI  - Toward the rational design of functionalized pentacenes: reduction of the impact
      of functionalization on the reorganization energy.
AB  - For the widely studied high-carrier-mobility species, pentacene, it is found that
      perfluorination turned it into an n-type organic field-effect transistor (OFET),
      but doubled the internal reorganization energy (lambda) of the electron/hole
      hopping. Here, Cl- and N-functionalized pentacenes are designed to test two
      strategies that may reduce the impact of functionalization on lambda. Calculation
      results show that the strategies are feasible. Moreover, combined with crystal
      structure data of Cl- and N-functionalized aromatic compounds, it is concluded
      that compared to fluorination, the presence of Cl and N atoms in pentacene not
      only reduces the influence of functionalization on lambda and affords a larger
      window for tuning HOMO (highest occupied molecular orbital) and LUMO (lowest
      unoccupied molecular orbital) energies, but also provides the opportunity to
      promote pi-stacked structures through ClCl and C--HN interactions.

PMID- 16952120
TI  - Structure-activity relationship studies of 3-aroylindoles as potent antimitotic
      agents.
AB  - The concise synthesis and structure-activity relationship (SAR) studies of 3
      aroylindoles were carried out in an effort to improve the potency and solubility
      of anticancer drug candidate BPR0L075 (8) by exploring structure modifications
      through three regimens: substitution of the B ring, at the N1 position, and of
      the 3-carbonyl linker. The SAR information revealed that the methoxy group of the
      B ring could be replaced with an electron-donating group such as methyl (in
      compound 9) or N,N-dimethylamino (in compound 13) while retaining both strong
      cytotoxic and antitubulin activities. The introduction of amide (compounds 30-33)
      and carbamate (compounds 34-37) functionalities at the N1 position of 8 gave
      analogues with potent antiproliferative activities. The cytotoxic potency of 8
      was improved by replacing the carbonyl group with sulfide (compound 41) or oxygen
      (compound 43), indicating that the carbonyl moiety is important but not
      essential. The N,N-dimethylamino derivative 13 not only displayed potent
      cytotoxicity and antitubulin activity, but also showed a markedly improved
      physicochemical profile relative to the parent compound.

PMID- 16952121
TI  - Self-waveguided photoemission and lasing of organic crystalline wires obtained by
      an improved expitaxial growth method.

PMID- 16952122
TI  - Adhesion on the nano- and macroscale: interaction between copper and SAN/SMAh
      copolymers.

PMID- 16952123
TI  - The in vitro effects of a bimodal contrast agent on cellular functions and
      relaxometry.
AB  - The in vivo monitoring of cell survival and migration will be essential to the
      translation of cell-based therapies from the laboratory to clinical studies. The
      pre-labeling of cells with magnetic resonance imaging (MRI) contrast agents
      renders them visible in vivo for serial cellular imaging. However, little is
      known about the impact of the presence of these metal particles inside
      transplanted cells. The use of the bimodal contrast agent GRID made it possible
      to demonstrate by means of fluorescent microscopy and inductively coupled plasma
      mass spectrometry (ICP-MS) that, after 16 h of incubation (without the use of a
      transfection agent), neural stem cells (NSCs) were saturated and no longer
      incorporated particles. With this maximal uptake, no significant effect on cell
      viability was observed. However, a significant decrease in proliferation was
      evident in cells that underwent 24 h of labeling. A significant increase in
      reactive oxygen species was observed for all GRID labeling, with a very
      significant increase with 24 h of labeling. GRID labeling did not affect cell
      motility in comparison with PKH26-labeled NSCs in a glioma-based migration assay
      and also allowed differentiation into all major cell types of the brain. GRID
      labeled cells induced a signal change of 47% on T(2) measurements and allows a
      detection of cell clusters of approximately 220 cells/microl. Further in vivo
      testing will be required to ensure that cell labeling with gadolinium-based MRI
      contrast agents does not impair their ability to repair.

PMID- 16952124
TI  - Continuous symmetry analysis of NMR chemical shielding anisotropy.
AB  - Molecular symmetry is a key parameter which dictates the NMR chemical shielding
      anisotropy (CSA). Whereas correlations between specific geometrical features of
      molecules and the CSA are known, the quantitative correlation with symmetry--a
      global structural feature--has been unknown. Here we demonstrate a CSA/symmetry
      quantitative relation for the first time: We study how continuous deviation from
      exact symmetry around a nucleus affects its shielding. To achieve this we
      employed the continuous symmetry measures methodology, which allows one to
      quantify the degree of content of a given symmetry. The model case we use for
      this purpose is a population of distorted SiH(4) structures, for which we follow
      the (29)Si CSA as a function of the degree of tetrahedral symmetry and of square
      planar symmetry. Quantitative correlations between the degree of these symmetries
      and the NMR shielding parameters emerge.

PMID- 16952125
TI  - On the mechanism of the ascorbic acid-induced release of nitric oxide from N
      nitrosated tryptophan derivatives: scavenging of NO by ascorbyl radicals.
AB  - During the past years, there has been increasing interest in endogenous nitric
      oxide storage compounds. Recently, we briefly reported on the ascorbate-dependent
      release of nitric oxide ((.)NO) from N-nitrosotryptophan derivatives. In the
      present study, the underlying mechanism of (.)NO release is studied in more
      detail, primarily utilizing N-acetyl-N-nitrosotryptophan (NANT) as a model
      compound. The initial rate of the ascorbate-induced release of nitric oxide has
      been found to correspond to the rate of NANT decay. In this process, N
      acetyltryptophan (NAT) is produced almost quantitatively. The final yield of
      nitrite amounted to around 90 % with respect to the applied amount of NANT.
      However, the total release of nitric oxide was only 60 %, as determined by using
      an FNOCT-4(fluorescent nitric oxide cheletropic trap number 4) assay. Besides
      nitric oxide, a second volatile product, dinitrogen oxide (N(2)O), has been
      identified by using (15)N NMR spectrometry, strongly indicating the intermediacy
      of nitroxyl (HNO). The formation of intermediate ascorbyl radical anions during
      the NANT-ascorbate reaction has been monitored by using ESR spectrometry.
      Unexpectedly, it was found that the primary oxidized product of vitamin C,
      dehydroascorbic acid (DHA), efficiently consumes nitric oxide. Since ESR
      spectrometry further revealed that ascorbyl radical anions are also generated
      during the spontaneous decay of DHA, the DHA-nitric oxide reaction is related to
      recombination of (.)NO with the thus formed ascorbyl radical anions. A
      conclusively established mechanism of the NANT-ascorbate reaction is presented,
      with O-nitrosoascorbate as a key intermediate, as additionally supported by CBS
      QB3 calculations. The present study suggests that vitamin C and its oxidation
      products can chemically counterbalance endogenous nitric oxide levels.

PMID- 16952126
TI  - Catalytic P--H activation by Ti and Zr catalysts.
AB  - Catalytic dehydrocoupling of phosphines was investigated using the anionic
      zirconocene trihydride salts [Cp*2Zr(mu-H)3Li]3 (1 a) or [Cp*2Zr(mu-H)3K(thf)4]
      (1 b), and the metallocycles [CpTi(NPtBu3)(CH2)4] (6) and [Cp*M(NPtBu3)(CH2)4]
      (M=Ti 20, Zr 21) as catalyst precursors. Dehydrocoupling of primary phosphines
      RPH2 (R=Ph, C6H2Me3, Cy, C10H7) gave both dehydrocoupled dimers RP(H)P(H)R or
      cyclic oligophosphines (RP)n (n=4, 5) while reaction of tBu3C6H2PH2 gave the
      phosphaindoline tBu2(Me2CCH2)C6H2PH 9. Stoichiometric reactions of these catalyst
      precursors with primary phosphines afforded [Cp*2Zr((PR)2)H][K(thf)4] (R=Ph 2, Cy
      3, C6H2Me3 4), [Cp*2Zr((PPh)3)H][K(thf)4] (5), [CpTi(NPtBu3)(PPh)3] (7) and
      [CpTi(NPtBu3)(mu-PHPh)]2 (8), while reaction of 6 with (C6H2tBu3)PH2 in the
      presence of PMe3 afforded [CpTi(NPtBu3)(PMe3)(P(C6H2tBu3)] (10). The secondary
      phosphines Ph2PH and (PhHPCH2)2CH2 also undergo dehydrocoupling affording (Ph2P)2
      and (PhPCH2)2CH2. The bisphosphines (CH2PH2)2 and C6H4(PH2)2 are dehydrocoupled
      to give (PCH2CH2PH)2)(12) and (C6H4P(PH))2 (13) while prolonged reaction of 13
      gave (C6H4P2)(8) (14). The analogous bisphosphine Me2C6H4(PH)2 (17) was prepared
      and dehydrocoupling catalysis afforded (Me2C6H2P(PH))2 (18) and subsequently
      [(Me2C6H2P2)2(mu-Me2C6H2P2)]2 (19). Stoichiometric reactions with these
      bisphosphines gave [Cp*2Zr(H)(PH)2C6-H4][Li(thf)4] (22), [CpTi(NPtBu3)(PH)2C6H4]2
      (23) and [Cp*Ti(NPtBu3)(PH)2C6H4] (24). Mechanistic implications are discussed.

PMID- 16952127
TI  - Probing structural effects on replication efficiency through comparative analyses
      of families of potential self-replicators.
AB  - A formidable synthetic apparatus for the creation of nanoscale molecular
      structures and supramolecular assemblies through molecular structures can
      potentially be created from systems that are capable of parallel
      automultiplication (self-replication). In order to achieve this goal, a detailed
      understanding of the relationship between molecular structure and replication
      efficiency is necessary. Diastereoisomeric templates that are capable of specific
      and simultaneous autocatalysis have been synthesised. A systematic experimental
      and theoretical evaluation of their behaviour and that of structurally-related
      systems reveals the key determinants that dictate the emergence of self
      replicative function and defines the structural space within which this behaviour
      is observed.

PMID- 16952128
TI  - Exploiting noninnocent (E,E)-dibenzylideneacetone (dba) effects in palladium(0)
      mediated cross-coupling reactions: modulation of the electronic properties of dba
      affects catalyst activity and stability in ligand and ligand-free reaction
      systems.
AB  - The reactivity of palladium(0) complexes, [Pd(0) (2)(dba-n,n'-Z)(3)] (n,n'-Z=4,4'
      F; 4,4'-CF(3); 4,4'-H; 4,4'-MeO) and [Pd(0)(dba-n,n'-Z)(2)] (n,n'-Z=4,4'-CF(3);
      4,4'-H; 3,3',5,5'-OMe), used as precursor catalysts with suitable donor ligands
      (e.g. phosphines, N-heterocyclic carbenes), has been correlated in several
      palladium(0)-mediated cross-coupling processes. Increasing the electron density
      on the aryl moiety of the dba-n,n'-Z ligand increases the overall catalytic
      activity in the majority of these processes. This effect primarily derives from
      destabilization of the L(n)Pd(0)-eta(2)-dba interaction (in dpi-pi* synergic
      bonding, n=1 or 2), which ultimately increases the global concentration of
      catalytically active L(n)Pd(0) available for reaction with aryl halide in the
      first committed step in the general catalytic cycle(s) (oxidative addition).
      Decreasing electron density on the aryl moiety of the dba-n,n'-Z ligand
      stabilizes the Pd(0)-eta(2)-dba interaction, reducing catalytic activity. The
      specific type of dba-n,n'-Z ligand appears to also play a stabilizing role in the
      catalytic cycle, preventing Pd agglomeration, and increasing catalyst longevity.
      A subtle balance therefore exists between the L(n)Pd(0) concentration (and the
      associated catalytic activity) and catalyst longevity. Changing the type of dba
      n,n'-Z ligand controls the concentration of L(n)Pd(0) and the rate of the
      oxidative addition step, and not other intimate steps within the catalytic
      cycle(s), for example, transmetallation (or carbopalladation) and reductive
      elimination. The role of dba-n,n'-Z ligands in Heck arylation is more convoluted
      and dependent on the alkene substrate employed, although trends have emerged.
      Changes in the structure of dba-n,n'-Z had a minimal affect on Buchwald-Hartwig
      aryl amination processes. A secondary Michael reaction of dba-n,n'-Z with amine
      and/or base effectively lessens its interference in the catalytic cycle.

PMID- 16952129
TI  - Local aromaticity in polycyclic aromatic hydrocarbons: electron delocalization
      versus magnetic indices.
AB  - The local aromaticity of benzenoid rings is examined by means of the Polansky
      index (P) and generalized population analysis (GPA). The results are found to
      agree very well with recently published circuit-condensed ring currents and
      magnetic-energetic aromaticity indices, but no correlation is found with nucleus
      independent chemical shifts (NICS). This is usually seen as a manifestation of
      the more general multidimensional nature of aromaticity. This paper examines the
      sources for the observed correlations, showing that some indices give conflicting
      results because they inherently reflect different phenomena.

PMID- 16952130
TI  - Inorganic-cored photoactive assemblies: synthesis, structure, and photochemical
      investigations on stannoxane-supported multifluorene compounds.
AB  - Organostannoxanes were used as inert supports for the preparation of
      multichromophore assemblies. The synthesis involves a single-step procedure and
      allows the preparation of compounds in which the number of chromophore units can
      be varied from one to six. Thus, the reactions of LCOOH (1-fluorenecarboxylic
      acid) or L'COOH (9-fluorenecarboxylic acid) with various organostannoxane
      precursors afforded the fluorenyl derivatives [Ph(3)SnO(2)CL] (1),
      [Ph(3)SnO(2)CL'] (2), [{nBu(3)SnO(2)CL''}(n)] (3), [{nBu(3)SnO(2)CL'}(n)] (4),
      [{tBu(2)Sn(OH)O(2)CL}(2)] (5), [{tBu(2)Sn(OH)O(2)CL'}(2)] (6),
      [{[nBu(2)SnO(2)CL](2)O}(2)] (7) [{[nBu(2)SnO(2)CL'](2)O}(2)] (8),
      [{nBuSn(O)O(2)CL}(6)] (9), and [{nBuSn(O)O(2)CL'}(6)] (10). Interestingly, the
      formation of 3 is accompanied by an unusual oxo-transfer reaction. The ligand L
      is oxidized at the 9-position. Compounds 1, 3, 5, 7, and 8 were characterized by
      X-ray crystallography. The solid-state structures of these compounds reveal rich
      supramolecular structures owing to multiple intermolecular interactions between
      the various supramolecular synthons present in these molecules. The optical
      behavior of 1-10 is primarily dictated by the fluorenyl periphery. These
      compounds display strong blue fluorescent emission in solution and blue-green
      fluorescent emission in the solid state. Fluorescence lifetimes of all of these
      compounds are on the nanosecond timescale, and this suggests that the emission
      originates from the singlet excited state to the ground state. Intermolecular
      interactions in the solid state lead to considerable broadening of the emission
      bands.

PMID- 16952131
TI  - Mechanism of the condensation of homocysteine thiolactone with aldehydes.
AB  - Chemical reactivity of homocysteine thiolactone (HTL) has been implicated in
      cardiovascular disease. Owing to its aminoacyl-thioester character, HTL undergoes
      facile electrophilic and nucleophilic reactions at its amino and activated
      carboxyl group, respectively. To gain insight into the mechanism of the reactions
      involving its amino group, the kinetics of the condensation of homocysteine
      thiolactone with formaldehyde, acetaldehyde, and pyridoxal phosphate, were
      analyzed in the pH range from 5 to 10. The reactions were first order with
      respect to HTL, aldehyde, and hydroxide ion concentrations. Of the two ionic
      species of HTL (pKa=6.67+/-0.05), the acid form HTL+ was approximately 100-fold
      more reactive than the base form HTL(0). The reactions of HTL with aldehydes
      involve intermediate adducts. The conversion of the intermediate carbinolamine to
      a product, 1,3-tetrahydrothiazine-4-carboxylic acid or its 2-substituted
      analogue, occurs in a two-step reaction. The first step involves hydrolysis of
      the thioester bond in the intermediate, facilitated by anchimeric assistance by
      the oxygen of the carbinolamine group of the intermediate. The second step
      involves an attack of the liberated thiolate on the aldehyde-derived carbon of
      the intermediate, affording 1,3-tetrahydrothiazine-4-carboxylic acid or its 2
      substituted analogue. An unusual feature of these reactions is that the formation
      of the carbinolamine group increases the reactivity of the thioester bond of HTL
      approximately 10(4)-fold. The facile formation of tetrahydrothiazines may
      contribute to HTL elimination from the human body.

PMID- 16952133
TI  - Prediction of ADMET Properties.
AB  - This Review describes some of the approaches and techniques used today to derive
      in silico models for the prediction of ADMET properties. The article also
      discusses some of the fundamental requirements for deriving statistically sound
      and predictive ADMET relationships as well as some of the pitfalls and problems
      encountered during these investigations. It is the intension of the authors to
      make the reader aware of some of the challenges involved in deriving useful in
      silico ADMET models for drug development.

PMID- 16952134
TI  - Structure-activity relationship studies on the immune stimulatory effects of base
      modified CpG toll-like receptor 9 agonists.
AB  - Synthetic oligodeoxynucleotides containing unmethylated deoxycytidylyl
      deoxyguanosine dinucleotide (CpG) motifs are able to stimulate potent immune
      responses through a signaling pathway involving Toll-like receptor 9 (TLR9). We
      have investigated the structure-activity relationship (SAR) of base-modified CpG
      oligonucleotides with TLR9 by measuring TLR9 activation by 20-mer
      oligonucleotides having just a single human recognition motif (5'-GTCGTT-3') in
      functional cell-based TLR9 assays. Substitution of guanine by hypoxanthine and 6
      thioguanine resulted in activity similar to the unmodified parent molecule,
      whereas purine, 2-aminopurine, 2,6-diaminopurine, and 8-oxo-7,8-dihydroguanine
      substitution resulted in approximately 40-60 % reduction in activity, and 7
      deazaguanine substitution led to the strongest (80 %) reduction in TLR9
      stimulation. Furthermore, none of the investigated modifications at C5 and N4 of
      cytosine were well tolerated with respect to human TLR9 stimulation. Our results
      are compatible with a SAR model in which guanine is recognized by the Hoogsteen
      site, and C5 is most critical for recognition of cytosine. In addition, we found
      significant species-specific differences between human and murine TLR9
      recognition, which demonstrates the importance of choosing appropriate assay
      systems for SAR studies.

PMID- 16952137
TI  - Platensimycin, a new antibiotic and "superbug challenger" from nature.

PMID- 16952136
TI  - Determination of the bound conformation of a competitive nanomolar inhibitor of
      mycobacterium tuberculosis type II dehydroquinase by NMR spectroscopy.
AB  - The synergy between tuberculosis and the AIDS epidemic, along with the surge of
      multidrug-resistant isolates of M. tuberculosis, has reaffirmed tuberculosis as a
      primary public health threat. It is therefore necessary to discover new, safe,
      and more efficient antibiotics against this disease. On the other hand, mapping
      the dynamic interactions of inhibitors of a target protein can provide
      information for the development of more potent inhibitors and consequently, more
      potent potential drugs. In this context, the conformational binding of our
      previously reported nanomolar inhibitor of M. tuberculosis type II
      dehydroquinase, the 3-nitrophenyl derivative 1, was studied using saturation
      transfer difference (STD) and transferred NOESY experiments. These studies have
      shown that in the bound state, one conformation of those present in solution of
      the competitive nanomolar inhibitor 3-nitrophenyl derivative 1 is selected. In
      the bound conformation, the aromatic ring is slightly shifted from coplanarity,
      with the double bond and the nitro group of 1 oriented towards the double bond
      side.

PMID- 16952138
TI  - Identification of a potent agonist of the orphan nuclear receptor Nurr1.

PMID- 16952139
TI  - Gold-nanoparticle-enhanced current transport through nanometer-scale insulating
      layers.

PMID- 16952140
TI  - Correlation of biological activity with active site binding modes of geminal
      disulfone HIV-1 integrase inhibitors.

PMID- 16952141
TI  - Synthesis and biological evaluation of a multiantigenic Tn/TF-containing
      glycopeptide mimic of the tumor-related MUC1 glycoprotein.

PMID- 16952144
TI  - Protection from autoimmunity: immunological indifference versus T-cell mediated
      suppression?
AB  - A long-held dogma was that immune tolerance could only be achieved through
      central deletion of potentially reactive cells at their site of origin, a concept
      supported by the direct demonstration of natural negative selection in bone
      marrow and thymus; however, it is now extensively documented that although
      deletion mechanisms ensure the elimination of most autoreactive cells, this
      purging is far from complete. There are major immune mechanisms that ensure
      tolerance in the periphery which are clearly non-deletional. A paper in this
      issue of the European Journal of Immunology demonstrates that T cell-mediated
      immunoregulation involving in particular the CTLA-4 signaling pathway plays a key
      role in controlling the pathogenic potential of fully differentiated autoreactive
      T cells.

PMID- 16952145
TI  - Control of graft-versus-host disease by regulatory T cells: which level of
      antigen specificity?
AB  - Regulatory T cells (Tregs) are essential to suppress harmful self-reactive T cell
      responses. A paper in this issue of the European Journal of Immunology analyzes
      the role of Tregs in preventing syngeneic graft-versus-host disease (sGVHD). In
      this Commentary, we address the role of antigen specificity of Tregs in this
      context as well as future protocols for successful allogeneic grafts
      transplantation. Such ideal interventions will hopefully retain a diverse
      repertoire of pathogen-specific T cells, while maintenance of self-, foreign- and
      alloantigen-specific Tregs ensures life-long graft tolerance.

PMID- 16952147
TI  - Presence of a thermoregulatory hot spot in the prothorax of the large carpenter
      bee and the bumble bee.
AB  - In both the large carpenter bee (Xylocopa pubescens) and the bumblebee (Bombus
      terrestris), a hot spot was detected in the center of the prothorax on its dorsal
      external aspect. In both cases, the temperature in this hot spot was found to be
      greater than the ambient temperature and that at the tip of the gaster. In B.
      terrestris, it was higher by 9-10 degrees C from that at the gaster tip and by 15
      16 degrees C from the ambient temperature, while in X. pubescens the
      corresponding differences were 11-20 degrees C and 18-19 degrees C, respectively.
      The recorded thermal differences were not fixed but were rather variable,
      temporally as well as individually, but invariably all individuals measured
      showed these temperature differences. Furthermore, in none of the studied
      specimens was a hot spot detected in any part of the body other than the
      prothorax. From this hot spot in the prothorax, there is a cascade of
      temperatures in both directions, that is, anteriorly towards the head and
      posteriorly towards the gaster, with a graded drop in temperature in either
      direction. This article discusses possible reasons for the existence of such a
      hot spot in this particular location (the prothorax), its role or function, and
      its mode of operation. The authors speculate that it is a thermoregulatory center
      (for heating or cooling) that might be present in possibly all Hymenoptera that
      spend a considerable part of their life flying, regardless of whether they are
      social, parasocial, or solitary.

PMID- 16952148
TI  - Testing and improving experimental parameters for the use of low molecular weight
      targets in array-CGH experiments.
AB  - Array-comparative genomic hybridization (CGH) has evolved as a useful technique
      for the detection and characterization of deletions, and, to a lesser extent, of
      duplications. The resolution of the technique is dictated by the genomic distance
      between targets spotted on the microarray, and by the targets' sizes. The use of
      region-specific, high-resolution microarrays is a specific goal when studying
      regions that are prone to rearrangements, such as those involved in deletion
      syndromes. The aim of the present study was to evaluate the best experimental
      conditions to be used for array-CGH analysis using low molecular weight (LMW)
      targets. The parameters tested were: the target concentration, the way LMW
      targets are prepared (either as linearized plasmids or as purified PCR products),
      and the way the targets are attached to the array-CGH slide (in a random fashion
      on amino-silane coated slides, or by one amino-modified end on epoxysilane-coated
      slides). As a test case, we constructed a microarray harboring LMW targets
      located in the CREBBP gene, mutations of which cause the Rubinstein-Taybi
      syndrome (RTS). From 10 to 15% of RTS patients have a CREBBP deletion. We showed
      that aminosilane- and epoxysilane-coated slides were equally efficient with
      targets above 1,000 bp in size. On the other hand, with the smallest targets,
      especially those below 500 bp, epoxysilane-coated slides were superior to
      aminosilane-coated slides, which did not allow deletion detection. Use of the
      high resolution array allowed us to map intragenic breakpoints with precision and
      to identify a very small deletion and a duplication that were not detected by the
      currently available techniques for finding CREBBP deletions.

PMID- 16952149
TI  - A study of the growth for the microalga Chlorella vulgaris by photo-bio
      calorimetry and other on-line and off-line techniques.
AB  - Calorimetry and other on-line techniques are used for the first time as
      complement to the traditional off-line methods in order to follow the growth of
      the green Chlorella vulgaris microalgae. A 2-L photo-bio-reactor was adapted from
      a commercial calorimeter used previously to study heterotrophic microbial growth.
      An external source of light was added to favor the photosynthesis of the
      autotrophic cells. Heterotrophic growth was also tested with external glucose in
      the broth. A third mode, mixotrophic, allowed faster autotrophic plus
      heterotrophic growth. Calorimetric measurements were performed considering the
      corresponding calibrations in order to consider only the energy involved during
      the microalgal growth. The three different modes of Chlorella cultures were
      energetically characterized. Besides calorimetry, the weight of diluted nitric
      acid added to maintain the pH of the culture was correlated with the cellular
      growth and the nitrogen composition of the algae. Additionally, the on-line
      infrared spectroscopy proved to be an efficient technique to follow the
      composition of the broth in glucose, nitrates, and phosphates. These results were
      compared and complemented with some classic off-line techniques used to track
      this kind of cultures.

PMID- 16952150
TI  - Application of cellulases from an alkalothermophilic Thermomonospora sp. in
      biopolishing of denims.
AB  - Use of cellulase for denim washing is a standard eco-friendly technique to
      achieve desirable appearance and softness for cotton fabrics and denims. But
      enzymatic washing of denim till date involved acid cellulase (Trichoderma reesei)
      and neutral cellulase (Humicola isolens) the use of which has a drawback of
      backstaining of the indigo dye on to the fabric. Though it has been suggested
      that pH is a major factor in controlling backstaining there are no reports on use
      of cellulase under alkaline conditions for denim washing. In this study for the
      first time an alkali stable endoglucanase from alkalothermophilic Thermomonospora
      sp. (T-EG) has been used for denim biofinishing under alkaline conditions. T-EG
      is effective in removing hairiness with negligible weight loss and imparting
      softness to the fabric. Higher abrasive activity with lower backstaining was a
      preferred property for denim biofinishing exhibited by T-EG. The activities were
      comparable to acid and neutral cellulases that are being regularly used. The
      enzyme was also effective under non-buffering conditions which is an added
      advantage for use in textile industry. A probable mechanism of enzymatic
      finishing of cotton fabric has been represented based on the unique properties of
      T-EG.

PMID- 16952151
TI  - Measurement of fast dynamic intracellular pH in Saccharomyces cerevisiae using
      benzoic acid pulse.
AB  - pH affects many processes on cell metabolism, such as enzyme kinetics. To enhance
      the understanding of the living cells, it is therefore indispensable to have a
      method to monitor the pH in living cells. To accomplish this, a dynamic
      intracellular pH measurement method applying low concentration benzoic acid pulse
      was developed. The method was thoroughly validated and successfully implemented
      for measuring fast dynamic intracellular pH of Saccharomyces cerevisiae in
      response to a glucose pulse perturbation performed in the BioSCOPE set-up. Fast
      drop in intracellular pH followed by partial alkalinization was observed
      following the pulse. The low concentration benzoic acid pulse which was
      implemented in the method avoids the undesirable effects that may be introduced
      by benzoic acid to cell metabolism.

PMID- 16952152
TI  - Protein instability during HIC: hydrogen exchange labeling analysis and a
      framework for describing mobile and stationary phase effects.
AB  - Unfolding of marginally stable proteins is a significant factor in commercial
      application of hydrophobic interaction chromatography (HIC). In this work,
      hydrogen-deuterium isotope exchange labeling has been used to monitor protein
      unfolding on HIC media for different stationary phase hydrophobicities and as a
      function of ammonium sulfate concentration. Circular dichroism and Raman
      spectroscopy were also used to characterize the structural perturbations
      experienced by solution phase protein that had been exposed to media and by
      protein adsorbed on media. As expected, greater instability is seen on
      chromatographic media with greater apparent hydrophobicity. However, increased
      salt concentrations also led to more unfolding, despite the well-known
      stabilizing effect of ammonium sulfate in solution. A thermodynamic framework is
      proposed to account for the effects of salt on both adsorption and stability
      during hydrophobic chromatography. Using appropriate estimates of input
      quantities, analysis with the framework can explain how salt effects on stability
      in chromatographic systems may contrast with solution stability.

PMID- 16952153
TI  - Production of adeno-associated viral vectors in insect cells using triple
      infection: optimization of baculovirus concentration ratios.
AB  - The production of viral vectors or virus-like particles for gene therapy or
      vaccinations using the baculovirus expression system is gaining in popularity.
      Recently, reports of a viral vector based on adeno-associated virus (AAV)
      produced in insect cells using the baculovirus expression vector system have been
      published. This system requires the triple infection of cells with baculovirus
      vectors containing the AAV gene for replication proteins (BacRep), the AAV gene
      for structural proteins (BacCap), and the AAV vector genome (BacITR). A
      statistical approach was used to investigate the multiplicities of infection of
      the three baculoviruses and the results were extended to the production of AAVs
      containing various transgenes. Highest AAV yields were obtained when BacRep and
      BacCap, the baculovirus vectors containing genes that code for proteins necessary
      for the formation of the AAV vector, were added in equal amounts at high
      multiplicities of infection. These combinations also resulted in the closest
      ratios of infectious to total AAV particles produced. Overexpression of the AAV
      structural proteins led to the production of empty AAV capsids, which is believed
      to overload the cellular machinery, preventing proper encapsidation of the AAV
      vector transgene, and decreased the viability of the insect cells. Delaying the
      input of BacCap, to reduce the amount of capsids produced, resulted in lower
      infectious AAV titers then when all three baculoviruses were put into the system
      at the same time. The amount of BacITR added to the system can be less than the
      other two without loss of AAV yield.

PMID- 16952154
TI  - The American society of cytopathology's future: cutting edge or damage control?

PMID- 16952155
TI  - Comparison of human papillomavirus distribution in cytologic subgroups of low
      grade squamous intraepithelial lesion.
AB  - BACKGROUND: Low-grade squamous intraepithelial lesion (LSIL) subsumes the
      formerly delineated cytologic categories of human papillomavirus (HPV)-associated
      cell changes (koilocytotic atypia) and low-grade dysplasia/cervical
      intraepithelial neoplasia (CIN) Grade 1 (CIN1). In this study, the objective was
      to determine whether these 2 morphologic subcategories are characterized by
      differences in risk for CIN3 and/or HPV type distribution. METHODS: Within the
      Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous
      Intraepithelial Lesion Triage Study, all cytologic interpretations of HPV
      cellular changes and CIN1 rendered by any of the pathology reviewers (community
      laboratory, clinical center, or Pathology Quality-Control Group) on referral
      Papanicolaou (Pap) tests or enrollment ThinPrep Pap tests were included for
      analysis. HPV testing was performed by Hybrid Capture 2 (HC2) and by polymerase
      chain reaction based reverse-line blot analysis for 27 HPV types. The absolute
      risks of cumulative detection of CIN3 or cancer (CIN3 +) and CIN2 or worse (CIN2
      +) over 2 years of follow-up were calculated for the various cytologic
      interpretations. RESULTS: For each review group and cytology preparation, most
      LSIL interpretations (from approximately 2 of 3 interpretations to 3 of 4
      interpretations) were subcategorized as CIN1 rather than HPV cellular changes.
      HPV type 16 (HPV-16) was the most common HPV type and was identified in 21% to
      24% of CIN1 and in 14% to 18% of HPV cellular changes. Nononcogenic types were
      identified alone in from 9% to 11% of CIN1 compared with 17% to 20% of HPV
      cellular change. The absolute risks of CIN1 and HPV cellular changes for
      cumulatively detected CIN3 + ranged from 12% to 16% for CIN1 and from 6% to 9%
      for HPV cellular changes. CONCLUSIONS: Both cytologic subcategories of LSIL were
      associated predominantly with oncogenic HPV types; however, the proportion of
      nononcogenic HPV types was lower and the absolute risks for CIN3 + were higher
      for CIN1 compared with HPV cellular changes. The concordance in subcategorizing
      LSIL was low, and the authors concluded that the diagnostic distinction is of
      limited clinical utility for individual patient management.

PMID- 16952156
TI  - Modification of cocaine-induced behavioral and neurochemical effects by
      serotonin1A receptor agonist/antagonist in mice.
AB  - Administration of cocaine causes a locomotor stimulant effect and increases
      extracellular levels of serotonin (5-HT) and dopamine (DA) in the brains of
      rodents. Previous studies show that 5-HT1A receptor agonist and antagonist modify
      the cocaine-induced behavioral and neurochemical effects in the rats. However,
      the role of the 5-HT system on the effects of cocaine has not been studied in the
      prefrontal cortex. The present study examined in ddY-strain male mice the effects
      of the 5-HT1A receptor agonist osemozotan and the receptor antagonist WAY100635
      on cocaine-induced locomotor stimulant effect and increases in extracellular
      levels of 5-HT and DA in the prefrontal cortex. The cocaine-induced locomotor
      stimulant effect was attenuated by osemozotan and enhanced by WAY100635. The
      cocaine-induced increase in extracellular levels of 5-HT was attenuated by
      osemozotan, and enhanced by WAY100635. The cocaine-induced increase in
      extracellular levels of DA was enhanced by osemozotan, but not affected by
      WAY100635. These results suggest that the prefrontal 5-HT system plays a pivotal
      role in the locomotor stimulant effect of cocaine in mice.

PMID- 16952157
TI  - Dopamine (D2/3) receptor agonist positron emission tomography radiotracer [11C]
      (+)-PHNO is a D3 receptor preferring agonist in vivo.
AB  - [11C]PHNO is a recently introduced agonist to image DA D2-like receptors with
      Positron Emission Tomography (PET). In cats and humans, [11C]PHNO revealed an
      atypical distribution compared to radiolabeled D2-like antagonists (such as
      [11C]raclopride) or other D2-like agonists (such as [11C]NPA), as it displayed
      unusual high binding in the globus pallidus (GP). The goal of this study was to
      assess the pharmacological nature of the binding of [11C]PHNO in the GP in
      nonhuman primates. As previously reported in humans, [11C]PHNO equilibrium
      specific to nonspecific equilibrium partition coefficients (V3'') in baboons was
      much higher in GP (3.88 +/- 1.15) than in the dorsal striatum (DST, 2.07 +/-
      0.43), whereas the reverse was true for [11C]raclopride (1.48 +/- 0.41 in GP,
      2.56 +/- 0.91 in DST) and [11C]NPA (0.87 +/- 0.19 in GP, 1.02 +/- 0.13 in DST).
      Administration of unlabeled raclopride resulted in similar reductions of [11C]
      PHNO V3'' and [11C]raclopride V3'' in both the GP and the DST. This observation
      demonstrated that the [11C]PHNO binding in the GP was specific to D2-like
      receptors. To evaluate the respective contribution of D3 and D2 receptors to the
      binding potential (BP) of [11C]PHNO and [11C]raclopride, experiments were carried
      out with the selective D3 partial agonist 1-(4(2-Napthoylamino)butyl)-4-(2
      methoxyphenyl)-1A-piperazine HCL (BP897). BP897 reduced [11C]raclopride V3'' by
      29% +/- 9%, 19% +/- 8%, and 10% +/- 7% in GP, VST, and DST, respectively, a
      result consistent with expectation from postmortem studies (D3/D2 ratio in GP >
      VST > DST). BP897 reduced [11C]PHNO V3'' by 57% +/- 11%, 30% +/- 11%, and 13% +/-
      8% in GP, VST, and DST, respectively, indicating that the D3 receptor
      contribution to [11C]PHNO signal is higher than that of [11C]raclopride. From
      these experiments we conclude that [11C]PHNO is a D3 preferring agonist, and that
      this property explains the high GP signal not observed with [11C]raclopride or
      [11C]NPA. This property might contribute to its higher vulnerability to
      endogenous DA compared to [11C]raclopride and [11C]NPA.

PMID- 16952158
TI  - Lack of neuropeptide Y attenuates the somatic signs of opiate withdrawal.
AB  - Recent evidence suggests that neuropeptide Y (NPY) may be involved in the
      neurobiological responses to drugs of abuse. This study was designed to assess
      the possible contribution of NPY to opiate withdrawal behaviors. Here we report
      that mice lacking the NPY gene show normal conditioned place aversion to opiate
      withdrawal, but show attenuated opiate withdrawal somatic signs.

PMID- 16952159
TI  - Differential induction of long term synaptic plasticity in inhibitory synapses of
      the hippocampus.
AB  - Long term synaptic plasticity has been more extensively studied in excitatory
      synapses, but it is also a property of inhibitory synapses. Many inhibitory
      synapses target hippocampal pyramidal neurons of the CA1 region. They originate
      from several interneuron classes that subdivide the surface area that they target
      on the pyramidal cell. Thus, many interneurons preferentially innervate the
      perisomatic area and axon hillock of the pyramidal cells while others
      preferentially target dendritic branches and spines. Methods to preferentially
      activate dendritic or somatic inhibitory synapses onto pyramidal neurons have
      been devised. By using these methods, the present work demonstrates that a
      stimulation pattern that induces long term potentiation (LTP) in excitatory
      synapses of the Schaffer collaterals is also capable of inducing distinct types
      of long term plastic changes in different classes of inhibitory synapses:
      Induction of long term depression (LTD) was seen in dendritic inhibitory synapses
      whereas LTP was observed in somatic inhibitory synapses. These findings suggest
      that inhibitory synapses arising from different interneuron classes may respond
      to the same stimulus according to their specific plastic potential enabling a
      spatial combinatorial pattern of inhibitory effects onto the pyramidal cell.

PMID- 16952160
TI  - Subcellular distributions of adenosine A1 and A2A receptors in the rat
      dorsomedial nucleus of the solitary tract at the level of the area postrema.
AB  - Adenosine A1 and A2A receptors mediate distinct cardiovascular components of
      defense reactions that are ascribed, in part, to opposing actions within the
      nucleus tractus solitarius. To assess the cellular sites of relevance to these
      actions, we examined the light and electron microscopic immunolabeling of
      adenosine A1 and A2A receptors in the rat dorsomedial nucleus of the solitary
      tract at the level of the area postrema (dmNTS-AP), a region crucial for
      cardiovascular regulation involving vagal baroreceptor afferents.
      Immunoreactivity for each receptor was independently localized to distinct
      segments of plasma membranes and endomembranes in somatodendritic, axonal, and
      glial profiles. The dendritic labeling for each receptor also was detected within
      and near asymmetric, excitatory-type synapses. Of all peroxidase labeled profiles
      exclusive of somata, approximately 58% were A1- and 39% were A2A-labeled
      dendrites. Dendrites and astrocytic glia were the profiles that most often
      expressed both subtypes of adenosine receptors. The axonal labeling for A2A
      receptors was seen mainly in unmyelinated axons, whereas the A1 receptors were
      prominently localized within axon terminals. These terminals often formed single
      or multisynaptic excitatory-type junctions or single symmetric synapses on
      dendrites, a few of which expressed A1 and A2A receptors. These results provide
      the first ultrastructural evidence that A1 and A2A receptors have distributions
      conductive to their dual involvement in modulating the output of single neurons
      and glial function in the dmNTS-AP, where the predominate presynaptic effects of
      adenosine are mediated through A1 receptors.

PMID- 16952161
TI  - Quantification of serotonin 5-HT1A receptors in monkey brain with [11C](R)-(-)
      RWAY.
AB  - [11C](R)-(-)-RWAY ([11C]2, 3, 4, 5, 6, 7-hexahydro-1{4-[1[4-(2-methoxyphenyl)
      piperazinyl]]-2-phenylbutyry}-1H-azepine) is a new radioligand for imaging brain
      5-HT1A receptors with positron emission tomography. In [11C](R)-(-)-RWAY, the
      direction of the amide bond is expected to reduce metabolism by hydrolysis while
      allowing easy 11C-labeling at the methoxy position. The purposes of this study
      were to evaluate different tracer kinetic models in nonhuman primates to quantify
      5-HT1A receptors with [11C](R)-(-)-RWAY and to test for the possible action of P
      glycoprotein (P-gp), one of the known efflux pumps at the blood-brain barrier.
      The brain uptake of radioactivity from [11C](R)-(-)-RWAY into 5-HT1A receptor
      rich brain regions was severalfold greater than for its antipode ([11C](S)-(+)
      RWAY) and could be displaced by receptor saturating doses of the selective 5-HT1A
      antagonist, WAY-100635. Pretreatment with tariquidar, a potent inhibitor of P-gp,
      increased brain uptake of [11C](R)-(-)-RWAY about 1.5-fold and the plasma free
      fraction about 1.8-fold. Thus, the effect of tariquidar on brain uptake may have
      been caused by displacement of the radioligand binding to plasma proteins.
      Mathematical modeling showed that the estimated values of regional binding
      potential were correlated strongly between two-tissue compartment model and
      multilinear reference tissue model, and thus, supported the use of the cerebellum
      as a reference region.

PMID- 16952162
TI  - High doses of methamphetamine that cause disruption of the blood-brain barrier in
      limbic regions produce extensive neuronal degeneration in mouse hippocampus.
AB  - Histological examination of brain after a single high (40 mg/kg) dose of D
      methamphetamine (METH) was used to determine the relationships between blood
      brain barrier (BBB) disruption, hyperthermia, intense seizure activity, and
      extensive degeneration that this exposure often produces. In very hyperthermic
      mice (body temperatures > 40.5 degrees C) exhibiting status epilepticus, increase
      in mouse IgG immunoreactivity (IgGIR) in the medial and ventral amygdala was
      observed within 90 min after METH exposure. In a few instances, where body
      temperature was in the 40.0 degrees C range, such IgGIR was also seen in animals
      that had exhibited status epilepticus. Variable increases in IgGIR, which
      correlated with neurodegeneration, also occurred within 12 h in the hippocampus,
      indicating BBB disruption in this region also. Degenerating neurons, Fluoro-Jade
      C (FJ-C) labeled, were first detected 4 h after METH in the amygdala and
      hippocampus. Extensive neurodegeneration occurred in the amygdaloid and
      hippocampal pyramidal cell regions in animals with marked IgGIR increase in these
      regions by 12 and 24 h after METH. A very rapid activation of brain microglia
      and/or infiltration of macrophages in regions of notable IgGIR increase with
      intense neurodegeneration were seen within 24 h. The phagocytosis rate of neurons
      in the hippocampus was so rapid that FJ-C labeling was virtually nonexistent 3
      days after METH. METH did not produce IgGIR increase or neurodegeneration in the
      limbic regions in the absence of hyperthermia and seizures. Thus, high doses of
      METH can cause damage to the BBB when hyperthermia occurs, resulting in rapid and
      extensive hippocampal and amygdalar damage. The BBB disruption in the medial
      amygdala occurs first, and may well be contributing to the induction and severity
      of seizures, while BBB disruption in the hippocampus is likely a result of the
      seizures and hyperthermia. This hippocampal damage should be sufficient to
      compromise learning and memory.

PMID- 16952163
TI  - Comparing sertindole to other new generation antipsychotics on preferential
      dopamine output in limbic versus striatal projection regions: mechanism of
      action.
AB  - The effects of acute administration of sertindole on DA output were examined in
      the shell part of the nucleus accumbens (NACS) and the striatum (STR), areas
      which are associated with limbic functions and motor control, respectively, by
      using in vivo differential normal pulse voltammetry in rats. The effect of
      sertindole was compared to those obtained with the reference antipsychotic drugs
      clozapine and haloperidol, new generation antipsychotics represented by
      risperidone, olanzapine, ziprasidone, quetiapine, and aripiprazole, as well as,
      with those of preferential D2/3, D4, 5-HT1A, 5-HT2A, 5-HT2C, alpha1, and alpha2
      receptor ligands. In similarity with the new generation antipsychotics,
      sertindole preferentially increase DA output in the NACS as compared to the STR
      whereas the opposite was true for haloperidol. The regional specific effect of
      the partial D2 receptor agonist aripiprazole was mainly driven by a decrease in
      striatal rather that by an increase in accumbal DA output. The selective 5-HT2A
      and D4 receptor antagonists MDL100,151 and Lu 38-012, respectively, both
      preferentially increased DA output in the NACS. Thus, the present results are in
      line with the hypothesis that 5-HT2A receptor antagonism is of importance for the
      observed limbic selectivity of new generation antipsychotics and, in turn, to
      their favorable clinical profile especially as regards extrapyramidal side
      effects (EPS) liability. For some compounds, blockade of D4 receptors may also
      play a role in this regard.

PMID- 16952164
TI  - Asian Tobacco Education and Cancer Awareness Research Special Population Network.
      A model for reducing Asian American cancer health disparities.
AB  - Asian Americans are the fastest growing and the second largest foreign-born
      ethnic group in the United States. Cancer is a leading cause of death among Asian
      Americans. The Asian Tobacco Education and Cancer Awareness Research (ATECAR)
      Special Population Network, Center for Asian Health, aimed to reduce or eliminate
      cancer health disparities in these diverse, underserved populations in
      Pennsylvania, New Jersey, Delaware, and New York. The ATECAR logic model was
      adapted from a variety of conceptual frameworks to develop and implement the
      network's multifaceted cancer health disparities research, training, awareness,
      and outreach programs. The model was the basis for the developmental phases of
      the network that included (1) needs assessment, infrastructure, and partnership
      building; (2) intervention research, training, and mentorship; and (3)
      evaluation, dissemination, and diffusion. Community involvement occurred at every
      operational level to ensure program and network sustainability. Between 2000 and
      2005, the ATECAR network consisted of 88 partners, representing a cross-section
      of Asian communities, academia, cancer centers, and health service agencies,
      ensuring a viable infrastructure for the network's multidimensional cancer health
      disparities programs. ATECAR's research covered tobacco control, cancer
      prevention and intervention, and clinical trials. More than 22 research projects
      were conducted and their results disseminated in peer-reviewed journals. ATECAR
      also trained 76 junior researchers and special population investigators and 1014
      community professionals in disparity issues. ATECAR's multimedia cancer awareness
      education program reached over 116,000 Asians. The ATECAR network's achievements
      have had a profound impact on Asian Americans and established a trend toward
      reducing cancer health disparities, especially among underserved Asian Americans.
      Cancer 2006. (c) 2006 American Cancer Society.

PMID- 16952166
TI  - Incidence and risk factors for the development of prolonged and severe
      intrahepatic cholestasis after liver transplantation.
AB  - Predictive factors for intrahepatic cholestasis after orthotopic liver
      transplantation (OLT) have not yet been established. We sought to identify the
      incidence and risk factors associated with prolonged severe intrahepatic
      cholestasis (PSIC) after OLT. We assessed 428 consecutive patients undergoing
      their first OLT. PSIC was diagnosed if a serum bilirubin concentration was
      greater than 100 micromol/L and/or a 3-fold increase of alkaline phosphatase
      occurred within the first month after OLT and was sustained for at least 1 week
      in the absence of biliary complications. Multivariable logistic regression
      identified factors independently associated with PSIC. PSIC developed in 107
      patients (25%). Independent risk factors by multivariable analysis were
      intraoperative transfusion of cryoprecipitate and platelets; nonidentical blood
      group status; suboptimal organ appearance; inpatient status before
      transplantation; and bacteraemia in the first month after transplantation. In
      contrast, acute liver failure, older age, and higher levels of serum sodium and
      serum potassium were all associated with a reduced likelihood of developing PSIC
      in the first month. There were 47 deaths in the PSIC group (44%) as opposed to 65
      deaths in the non-PSIC group (20%) after OLT. A poor preoperative clinical status
      in conjunction with a suboptimal graft was associated with PSIC after OLT.
      Avoidance of suboptimal livers and ABO nonidentical grafts for young patients
      with poor synthetic function and for pretransplant inpatients may lessen this
      complication and reduce the associated early mortality.

PMID- 16952165
TI  - Electrochemical screening of recombinant protein solubility in Escherichia coli
      using scanning electrochemical microscopy (SECM).
AB  - A microbial array chip with collagen gel spots entrapping living Escherichia coli
      (E. coli) DH5alpha was applied for the screening of recombinant protein
      solubilities. The alpha-fragment of beta-galactosidase (betaGal) was fused to the
      target protein, namely, maltose-binding protein (MBP), to monitor the solubility
      of MBP. Scanning electrochemical microscopy (SECM) was used to detect the release
      of p-aminophenol from E. coli cells catalyzed by intracellular betaGal.
      Comparison of the SECM-based method with the Western blotting-based method
      indicated that the current response obtained using SECM increased with an
      increase in the betaGal activity and therefore, with the soluble fraction of MBP
      in the host cells.

PMID- 16952167
TI  - Accuracy of magnetic resonance imaging for preoperative detection of portal vein
      thrombosis in liver transplant candidates.
AB  - The detection of main portal vein thrombosis (PVT) on preoperative imaging of
      liver transplant candidates has important technical implications for the
      transplantation procedure. Data are scarce regarding the accuracy of magnetic
      resonance imaging (MRI) at detecting PVT. The aim of our study was to compare
      preoperative findings of the portal vein on MRI to operative findings at liver
      transplantation. Abdominal MRI and clinical records of 172 consecutive patients
      who received liver transplants between January 1999 and September 2004 were
      reviewed. Two radiologists independently evaluated the last abdominal magnetic
      resonance examinations obtained before liver transplantation, blinded to the
      original reading, operative findings, and clinical data. Findings on MRI were
      compared with intraoperative findings at transplantation. Main PVT was detected
      in 12 patients, in whom 8 were found to have thrombus at surgery, with 6
      requiring a jump graft or thrombectomy. Sensitivity and specificity of MRI for
      detecting main PVT were 100% and 98%, respectively. The cause of discordance
      between findings on MRI and at transplantation in 2 cases was a diminutive
      caliber of the main portal vein that was interpreted as recanalized chronic
      thrombosis on MRI. In conclusion, in our study group MRI detected PVT in all
      liver transplant recipients requiring jump grafts at transplantation. The major
      reason for a false-positive MRI was a diminutive but patent portal vein.

PMID- 16952168
TI  - Long-term effects of a midgestational asphyxial episode in the ovine fetus.
AB  - We and others have shown previously that fetuses at midgestation can survive 30
      min of complete umbilical cord occlusion, although hydrops fetalis (or gross
      fetal edema) results. To investigate whether this hydrops resolves by late
      gestation and if there are any long-term consequences of the asphyxial insult on
      the heart and kidneys, eight fetuses were subjected to 30 min of complete
      umbilical cord occlusion at 0.6 gestation (90 days; term 150 days) and were
      compared to a sham group (n = 10). During the occlusion period, fetuses became
      severely hypoxemic, hypercapnemic, and acidotic, with both blood pressure and
      heart rate decreasing. Most variables had returned to normal by 2-hr recovery. At
      129 +/- 1 days of gestation, approximately 40 days post occlusion, some fetuses
      were still slightly hydropic as skin fold measurements were increased (P < 0.01),
      although fetal body weight was not different from the sham group. The two groups
      had similar heart and kidney weights, ventricular cardiac myocyte nucleation, and
      glomerular number. By contrast, brain weight was reduced by 37% (P < 0.001) and
      the cerebral lateral ventricles were grossly dilated. Lungs were 50% smaller than
      in sham fetuses (P < 0.001). Thus, the hydrops that develops at midgestation as a
      result of a severe asphyxial episode can, but does not always, fully resolve by
      late gestation. Also, while fetuses at midgestation can survive this asphyxial
      episode with no long-term impact in renal or cardiac size, nephron number, or
      cardiomyocyte nucleation, the brain and lungs are severely affected.

PMID- 16952169
TI  - Heterogeneous postnatal transitions in myosin heavy chain isoforms within the
      rabbit temporalis muscle.
AB  - Postnatal changes in the fiber type composition and fiber cross-sectional area
      were investigated in the superficial (TEM1) and deep (TEM23) temporalis of male
      rabbits. It was hypothesized that, due to the transition from suckling to chewing
      during early postnatal development, the proportion of fast fiber types would
      decrease, while the proportion of fibers positive for myosin heavy chain (MyHC)
      cardiac alpha would increase, and that, due to the influence of testosterone
      during late postnatal development, the proportion of these alpha fibers would
      decrease again. Classification of the fibers types was performed by
      immunohistochemistry according to their MyHC content. The proportion of alpha
      fiber types significantly increased in both muscle portions from 2% and 8% for
      TEM1 and TEM23 at week 1 to 29% and 54% at week 8, respectively,. While in TEM1
      the proportion of this fiber type did not change thereafter, it decreased again
      to 27% in TEM23 at week 20. The change for the fast fiber types was opposite to
      that of the alpha fiber types. Significantly more MyHC IIX fibers were found in
      TEM1 than in TEM23 in adult rabbits. In the first 8 weeks, the cross-sectional
      areas of all fibers increased. After this period, only MyHC cardiac alpha + I
      fibers continued to increase significantly. It was concluded that there are
      developmental differences in the myosin heavy chain transitions of the two
      portions of the temporalis muscle.

PMID- 16952170
TI  - Horse soleus muscle: postural sensor or vestigial structure?
AB  - The soleus muscle of horses is rather diminutive with respect to the overall size
      of adjacent synergist muscles in the hind limb of the horse. Whether or not such
      a muscle might be vestigial or may be providing some essential function has not
      been determined. We have studied the horse's soleus muscle using histochemical
      (ATPase), immunocytochemical (myosin isoform identification), and SDS-PAGE
      analysis to demonstrate that it is largely composed of 100% type I, presumed slow
      twitch fibers. Only one soleus muscle studied (out of 13 adult horses) contained
      any type II muscle fibers. Given this consistent high percentage of slow
      oxidative fibers, we hypothesized that the soleus muscle could have a significant
      role in proprioceptive function, essentially functioning as a proprioceptive
      organ instead of a significant force-generating muscle during locomotion. We
      tested this by examining three whole soleus muscles and assessing their muscle
      spindle content, which proved to have a spindle index of about 12. This value
      provided equivocal support for the hypothesis since it did not approach values
      reported for other mammalian proprioceptive muscles that were approximately 40-50
      spindles per gram of muscle mass. Other parameters, such as motoneuron number and
      muscle unit size, may be useful in understanding these data.

PMID- 16952171
TI  - Dietary consistency and plasticity of masseter fiber architecture in postweaning
      rabbits.
AB  - Dietary consistency has been shown to influence cross-sectional area and fiber
      type composition of the masticatory muscles. However, little is known about the
      effects of dietary consistency on masticatory muscle fiber architecture. In this
      study, we explore the effects of dietary consistency on the internal architecture
      of rabbit masseter muscle. Because activity patterns of the rabbit chewing
      muscles show inter- and intramuscular heterogeneity, we evaluate if alterations
      in fiber architecture are homogeneous across various portions of the superficial
      masseter muscle. We compared masseter muscle fiber architecture between two
      groups of weanling rabbits raised on different diets for 105 days. One group was
      raised on a diet of ground rabbit pellets to model underuse of the masticatory
      complex, while the other group was fed a diet of intact pellets and hay blocks to
      model an overuse diet. In all portions of the superficial masseter, physiological
      cross-sectional areas (PCSAs) are greater in the overuse compared to underuse
      diet rabbits. Thus, the mechanical demands for larger muscle and bite forces
      associated with early and prolonged exposure to a tough diet are met by an
      increase in PCSA of the superficial masseter. The larger PCSA is due entirely to
      increased muscle mass, as the two rabbit groups show no differences in either
      fiber length or angle of pinnation. Thus, increasing pinnation angle is not a
      necessary biomechanical solution to improving muscle and bite force during
      growth. The change in PCSA but not fiber length suggests that variation in
      dietary consistency has an impact on maximum force production but not necessarily
      on excursion or contraction velocity.

PMID- 16952172
TI  - Mapping the imprint of bone remodeling by atomic force microscopy.
AB  - Understanding bone remodeling is essential for understanding bone as a whole.
      Bone remodeling takes place through a stepwise cellular process, with osteoclasts
      carving small cavities, also known as resorption pits, into the surface of
      trabecular bone, followed by osteoblasts, which refill the pits with new soft
      bone collagen matrix tissue (osteoid). The detailed structure of the surface in
      the frontier of a resorption pit before, during, and after the osteoid is being
      laid down is not well known. We present detailed atomic force microscope (AFM)
      images from the edge, the front end, and the bottom of a resorption pit in a
      human trabecular bone sample that showed signs of incomplete remodeling. The
      images reveal a scalloped surface left behind by the osteoclasts and the surface
      morphology of preexisting bone tissue and new bone tissue. In addition, we
      display the bone formation front in the pit showing the anchor points between the
      new bone and the existing bone. We also found evidence of microcracking in the
      front end of the pit, suggesting that microcracking was the initiator of this
      particular resorption pit. We anticipate that AFM may initiate a more detailed
      understanding of the influence of the remodeling process on the structure of
      bone, as well as a better understanding of the surface on which new bone tissue
      can be anchored.

PMID- 16952173
TI  - High-pressure freezing and freeze substitution of rat myocardium for immunogold
      labeling of connexin 43.
AB  - The value of high-pressure freezing (HPF) and freeze substitution (FS) for
      immunoelectron microscopy (immuno-EM) of the heart was investigated in bioptic
      specimens taken from isolated hearts of 0-, 5-, and 14-day-old rats at baseline
      and at 15, 30, 45, and 60 min after induction of ischemia. The target antigen
      chosen here was the gap junction protein connexin 43 (Cx43). After HPF and FS,
      immunogold labeling was applied for detection of Cx43. Gold particles associated
      with gap junction areas, free plasma membrane, and annular gap junctions (AGJs)
      were counted and distributions compared by contingency table analysis. HPF and FS
      resulted in excellent preservation of antigenicity for Cx43. The mostly good
      preservation of the ultrastructure was limited by mechanical damage at the border
      and by ice crystal formation in the center of the tissue blocks. In normal
      myocardium of newborns, gold particles associated with free plasma membrane were
      frequently observed, with AGJs only seldom. In older rats, the opposite relation
      was found. During ischemia, no distribution changes occurred in newborn or 14-day
      old rats. In 5-day-old rats, however, ischemia induced a shift of Cx43 from gap
      junction plaques to AGJs. In conclusion, HPF and FS are an ideal alternative to
      chemical fixation for immuno-EM as the excellent preservation of antigenicity is
      combined with a well-preserved ultrastructure. The results indicate that the
      process of degradation of gap junctions via AGJs gradually increases during
      postnatal rat heart development, a process that may be accelerated by ischemia in
      an early developmental state.

PMID- 16952174
TI  - Optimizing staging for hepatocellular carcinoma before liver transplantation: A
      retrospective analysis of the UNOS/OPTN database.
AB  - Assignment of liver allocation priority for hepatocellular carcinoma is
      predicated on accurate imaging staging. We analyzed radiographically defined
      stage (radiologic stage [RS]) at listing and most recent extension and pathologic
      stage (PS) data from 789 liver transplant recipients for whom no pretransplant
      ablative treatment was given. There were no predetermined imaging or pathological
      protocols in this retrospective analysis of wait list data. Seventy-two (9.1%),
      690 (87.5%), and 27 (3.4%) were listed as stage 1, 2 and >2, respectively.
      Computed tomography (CT) scan alone (46.4%), magnetic resonance image scan alone
      (37.1%), ultrasound alone (1.3%), and multiple imaging studies (15.2%) were used
      with no difference in time to transplant for listing or most recent scan among
      the recipient groups. Overall accuracy (RS = PS) was 44.1% and was not different
      if original listing RS or most recent RS was used for comparison with PS. No one
      type of imaging technique had superior accuracy (P = 0.13); however, CT scan used
      alone or in combination compared to not being used at all, had higher odds of
      being accurate (odds ratio [OR] 1.38 [1.03-1.84], P = 0.031). In addition,
      imaging done less than 90 days before transplant had higher odds of being
      accurate (OR 1.49 [1.06-2.08], P = 0.019) as did RS = 2 or 3 (OR 5.56 [2.70
      11.11], P < 0.0001). We observed considerable variation in RS accuracy among the
      United Network for Organ Sharing and Organ Procurement and Transplantation
      Network regions that is unexplained. In conclusion, current imaging requirements
      for RS prior to liver transplantation are unacceptably inaccurate. Future policy
      should require more accurate modalities or combinations of techniques.

PMID- 16952175
TI  - Documented deaths of hepatic lobe donors for living donor liver transplantation.
AB  - The actual risk of death in hepatic lobe donors for living donor liver
      transplantation (LDLT) is unknown because of the lack of a comprehensive
      database. In the absence of a definitive estimate of the risk of donor death, the
      medical literature has become replete with anecdotal reports of donor deaths,
      many of which cannot be substantiated. Because donor death is one of the most
      important outcomes of LDLT, we performed a comprehensive survey of the medical
      and lay literature to provide a referenced source of worldwide donor deaths. We
      reviewed all published articles from the medical literature on LDLT and searched
      the lay literature for donor deaths from 1989 to February 2006. We classified
      each death as "definitely," "possibly," or "unlikely" related to donor surgery.
      We identified 19 donor deaths (and one additional donor in a chronic vegetative
      state). Thirteen deaths and the vegetative donor were "definitely," 2 were
      "possibly," and 4 were "unlikely" related to donor surgery. The estimated rate of
      donor death "definitely" related to donor surgery is 0.15%. The rate of donor
      death which is "definitely" or "possibly" related to the donor surgery is 0.20%.
      This analysis provides a source document of all identifiable living liver donor
      deaths, provides a better estimate of donor death rate, and may provide an
      impetus for centers with unreported deaths to submit these outcomes to the liver
      transplantation community.

PMID- 16952176
TI  - Development and validation of a model predicting graft survival after liver
      transplantation.
AB  - This study aimed to develop and validate a comprehensive model that predicts
      survival after liver transplantation based on pretransplant donor and recipient
      characteristics. Complete data were available from the United Network for Organ
      Sharing for 20,301 persons who underwent liver transplantation in the United
      States between 1994 and 2003. Proportional-hazards regression was used to
      identify the donor and recipient characteristics that best predicted survival and
      incorporate these characteristics in a multivariate model. A data-splitting
      approach was used to compare survival predicted by the model to the observed
      survival in samples not used in the derivation of the model. A model was derived
      using 4 donor characteristics (age, cold ischemia time, gender, and
      race/ethnicity) and 9 recipient characteristics (age, body max index, model for
      end-stage liver disease score, United Network for Organ Sharing priority status,
      gender, race/ethnicity, diabetes mellitus, cause of liver disease, and serum
      albumin) that adequately predicted survival after liver transplantation in
      patients without hepatitis C virus, and a slightly different model was used for
      patients with hepatitis C virus. The models illustrate that variations in both
      pretransplant donor and recipient characteristics have a large effect on
      posttransplant survival. In conclusion, the models presented here can be used to
      derive scores that are proportional to the excess risk of graft loss after liver
      transplantation for potential donors, recipients, or donor/recipient
      combinations. The models may be used to inform liver transplant candidates and
      their doctors what posttransplant survival would be expected when a given donor
      is offered and may be particularly helpful for marginal or high-risk donors.

PMID- 16952177
TI  - Derivation of a risk index for the prediction of massive blood transfusion in
      liver transplantation.
AB  - Massive blood transfusion (MBT) remains a serious and common occurrence in liver
      transplantation surgery. This retrospective cohort study was undertaken to
      identify preoperative predictors of MBT and to develop a risk index for MBT in
      liver transplantation. Data were retrospectively collected on all liver
      transplantations carried out at a single institution between January 1998 and
      March 2004. Multivariable logistic regression analysis was used to identify
      independent predictor variables of MBT, defined as >/=6 units of red blood cell
      concentrate (RBC) in the first 24 hours of surgery. The model was internally
      validated by bootstrapping. Of the 460 liver transplant recipients, 193 (42%)
      received >/=6 units of RBC within 24 hours of surgery. Unadjusted analyses
      identified 12 preoperative predictors of MBT: age, height, gender, repeat
      transplantation, etiology of liver failure, and preoperative laboratory values
      (hemoglobin concentration, platelet count, international normalized ratio for
      prothrombin activity [INR], albumin, total bilirubin, and creatinine). In
      multivariable logistic regression, 7 independent predictors of MBT were
      identified: age (>40 years), hemoglobin concentration (</=10.0 g/dL), INR (1.2
      1.99, and >2.0), platelet count (</=70 x 10(9)/L), creatinine (>/=110 micromol/L
      for female subjects and >/=120 micromol/L for male subjects), albumin (< 28 g/L),
      and repeat transplantation. The area under the receiver-operating characteristic
      curve (ROC) for the model was 0.82. By using the regression beta coefficients to
      derive weights for each of these predictors, a risk index was developed that
      assigned each patient a score between 0 and 8. The ROC for this risk index was
      0.79. MBT in liver transplantation surgery can be accurately predicted by 7
      readily available preoperative predictors.

PMID- 16952178
TI  - Application of artificial neural network coupling particle swarm optimization
      algorithm to biocatalytic production of GABA.
AB  - The biotransformation of L-sodium glutamate (L-MSG) to gamma-aminobutyric acid
      (GABA) catalyzed by the cells of Lactobacillus brevis with higher glutamate
      decarboxylase activity was investigated. The results showed that pH, temperature,
      and FeSO(4) x 7H(2)O concentration had significantly positive effect on GABA
      yield. The individual and interactive effects of pH, temperature, and FeSO(4) x
      7H(2)O concentration were further optimized in terms of GABA yield. In the
      present work, an artificial neural network (ANN) and response surface methodology
      (RSM) models were developed, which incorporated pH, temperature, and FeSO(4) x
      7H(2)O concentration as input variables, and GABA yield as output variable. The
      optimized ANN topology included four neurons in the hidden layer and the best
      network architecture was 3-4-1. The trained ANN gave total root-mean square error
      (sigma) equal to 1.84 for GABA yield while the RSM gave sigma equal to 2.63. The
      results demonstrated a slightly higher prediction accuracy of ANN compared to
      RSM. The modeled maximum GABA yield was identified by applying particle swarm
      optimization algorithm to the ANN model developed. The modeled maximum GABA yield
      reached 91 mM under the following optimal conditions: 25 mL Na(2)HPO(4)-citric
      acid buffer (100 mM, pH 4.23), 120 mM L-MSG, 0.83 g/L FeSO(4) x 7H(2)O, 10 microM
      PLP, the resting cells obtained from a 60-h culture broth, 2.68 g dry cell weight
      (DCW)/L, and without agitation at 40 degrees C for 5 h. The previous high value
      of GABA yield that was observed was 81.8 mM. The optimized conditions allowed
      GABA yield to be increased from 81.8 to 90.57 mM after verification experiments
      test.

PMID- 16952179
TI  - Quantitative real-time PCR for rapid and accurate titration of recombinant
      baculovirus particles.
AB  - We describe the use of quantitative PCR (QPCR) to titer recombinant
      baculoviruses. Custom primers and probe were designed to gp64 and used to
      calculate a standard curve of QPCR derived titers from dilutions of a previously
      titrated baculovirus stock. Each dilution was titrated by both plaque assay and
      QPCR, producing a consistent and reproducible inverse relationship between C(T)
      and plaque forming units per milliliter. No significant difference was observed
      between titers produced by QPCR and plaque assay for 12 recombinant viruses,
      confirming the validity of this technique as a rapid and accurate method of
      baculovirus titration.

PMID- 16952180
TI  - Methodological analysis for determination of enzymatic digestibility of
      cellulosic materials.
AB  - Accurate measurement of enzymatic cellulose digestibility (X) is important in
      evaluating the efficiency of lignocellulose pretreatment technologies, assessing
      the performance of reconstituted cellulase mixtures, and conducting economic
      analysis for biorefinery processes. We analyzed the effect of sugars contained in
      enzymes solutions, usually added as a preservative, and random measurement errors
      on the accuracy of X calculated by various methods. The analysis suggests that
      exogenous sugars at levels measured in several commercial enzyme preparations
      significantly bias the results and that this error should be minimized by
      accounting for these sugars in the calculation of X. Additionally, a method of
      calculating X equating the ratio of the soluble glucose equivalent in the liquid
      phase after hydrolysis to the sum of the soluble glucose equivalent in the liquid
      phase and the insoluble glucose equivalent in the residual solid after hydrolysis
      was found to be the most accurate, particularly at high conversion levels (>ca.
      50%).

PMID- 16952181
TI  - Lipase/aluminum-catalyzed dynamic kinetic resolution of secondary alcohols.

PMID- 16952182
TI  - Direct observation of photochromic dynamics in the crystalline state of an
      organorhodium dithionite complex.

PMID- 16952184
TI  - Structurally characterized quadruple-stranded bisbidentate helicates.

PMID- 16952183
TI  - Metal-catalyzed asymmetric epoxidations of terminal olefins using hydrogen
      peroxide as the oxidant.

PMID- 16952185
TI  - Boron-containing two-photon-absorbing chromophores: electronic interaction
      through the cyclodiborazane core.

PMID- 16952186
TI  - Alkali-metal-mediated zincation of polycyclic aromatic hydrocarbons: synthesis
      and structures of mono- and dizincated naphthalenes.

PMID- 16952187
TI  - Hard and soft: biofunctionalized diamond.

PMID- 16952188
TI  - The molecular mechanism of the termination of insect diapause, part 1: A timer
      protein, TIME-EA4, in the diapause eggs of the silkworm Bombyx mori is a metallo
      glycoprotein.
AB  - TIME-EA4 is an ATPase that measures time intervals, functioning as a diapause
      duration clock in diapause eggs of the silkworm, Bombyx mori. Characterization of
      the primary and higher structures of the TIME-EA4 would be desirable to clarify
      the mechanism by which the protein measures the time intervals. In our current
      studies, the whole sequence of TIME-EA4 has been established as that of a metallo
      glycoprotein by combinational means involving peptide sequence analysis, nano
      HPLC-ESI-Q-TOF-MS and MS/MS, and cDNA dictation. The amino acid sequence of TIME
      EA4 showed 46-55 % homology with the reported proteins of the Cu,Zn-SOD
      (superoxide dismutase) family; in particular, the SOD active site (core domain)
      includes metal-binding amino acid ligands and a disulfide bond, and these
      structures are completely identical in Bombyx SOD, bovine SOD, and TIME-EA4
      proteins. We found, however, that TIME-EA4 contains one more copper ion than
      other SODs, as was proven under neutral nondenaturing conditions. ESI mass
      spectrometry revealed that the timer function was not in the SOD core domain. In
      addition, TIME-EA4 has an attached sugar chain, which is indispensable to its
      functioning as a timer protein.

PMID- 16952189
TI  - Impact of epimerization domains on the intermodular transfer of enzyme-bound
      intermediates in nonribosomal peptide synthesis.
AB  - Assembly of bioactive natural compounds through the action of nonribosomal
      peptide synthetases (NRPSs) relies on the specific interplay of modules and
      domains along these multiple mega-enzymes. As the C termini of several bacterial
      NRPSs often harbor epimerization (E) domains that generate D-amino acids, these
      seem to facilitate the ordered intermolecular enzymatic interaction and the
      directed transfer of intermediates. To elucidate this bifunctional role, E
      domains in recombinant bimodular proteins derived from the tyrocidine synthetase
      B were investigated. By utilizing sequent tryptic proteolysis and HPLC Fourier
      transform ion cyclotron resonance mass spectrometry (FTICR-MS), we could directly
      interrogate and determine the formation of intermediates attached to the TycB(3)
      PCP domain of wild-type TycB(2-3) and to the E domain exchange enzyme TycB(2-3)
      ATCAT/E(tycA). In addition, the two proteins and a version of TycB(2-3) fused to
      the communication-mediating (COM) domain of TycA were applied in product
      formation assays with TycB(1) to corroborate E domain impact on intermodular NRPS
      interaction. Significant functional differences between the C-terminal aminoacyl-
      and peptidyl-E domains were observed in terms of in trans interaction and
      misinitiation. E domains originating from elongation modules (peptidyl-E domains)
      seem to be optimized for regulation of the progression of peptide bond formation,
      epimerization, and intermediate transfer to the downstream module, whereas E
      domains of initiation modules (aminoacyl-E domains) impair upstream condensation
      and cause misinitiation. The selection of E domains is therefore decisive for
      successful application in biocombinatorial engineering of nonribosomal peptides.

PMID- 16952191
TI  - Understanding biology at the molecular level.

PMID- 16952190
TI  - A model for cell-surface-exposed carbohydrate moieties suitable for structural
      studies by NMR spectroscopy.
AB  - In the present study a synthetic glycolipid system is presented that can be
      readily incorporated into phospholipid micelles and that allows the study of cell
      surface-exposed carbohydrate units by high-resolution NMR techniques. Here, we
      present an efficient route for the synthesis of glycolipid compounds that contain
      mannose, mannobiose, or mannotriose coupled either directly to an alkyl chain or
      through a poly(ethylene glycol) linker. Furthermore, we have validated our model
      system by measuring the binding of cyanovirin N (CV-N), a cyanobacterial protein
      that binds with nanomolar affinity to the terminal arms of high-mannose
      structures of the HIV surface-envelope glycoprotein gp120, to glycolipids the
      carbohydrate portions of which comprise the corresponding high-mannose moieties.
      From the results of chemical-shift mapping with uniformly (15)N-labelled CV-N, we
      conclude that binding to the protein occurs at sites similar to those involved in
      binding the nonconjugated carbohydrates. We characterized the insertion of the
      glycolipids into dodecylphosphocholine (DPC) micelles by measuring translational
      diffusion, and we observed that the diffusion constants of the glycolipids were
      very similar to those of the DPC micelles themselves, but significantly deviated
      from those of the free glycolipids. We also present experimental proof that the
      glycolipids remain inserted in the micelles while binding to CV-N. Finally, by
      addition of a ligand that had a higher affinity to CV-N but which was not
      attached did not couple to a lipid anchor, CV-N could be released from the
      glycolipid and, hence, from the micelle-associated state.

PMID- 16952192
TI  - Energetic bicyclic azolium salts.
AB  - Bicyclic azoles, 2-methyl-5-(imidazol-1-yl)-2H-tetrazole (1), 2-methyl-5-(1,2,4
      triazol-1-yl)-2H-tetrazole (4), 1-methyl-5-(imidazol-1-yl)-1H-tetrazole (7), 1
      methyl-5-(1,2,4-triazol-1-yl)-1H-tetrazole (10), 1-methyl-4-nitro-2-(imidazol-1
      yl)-1H-imidazole (13), and 1-methyl-4-nitro-2-(1,2,4-triazol-1-yl)-1H-imidazole
      (16) were prepared. Their thermally stable azolium salts, 3, 6, 9, 12, 15, and 18
      21, with densities ranging between 1.519-1.674 g cm-3, were synthesized by
      quaternization with nitric or perchloric acid or with iodomethane followed by
      metathesis reactions with silver nitrate and silver perchlorate. The structures
      of 12 b and 21 b were confirmed by single-crystal X-ray analysis. The standard
      enthalpies of formation for some of the new salts were calculated by using the
      computationally feasible DFT(B3LYP) and MP2 methods in conjunction with an
      empirical approach based on densities of salts. The calculated values range from
      DeltaHdegreef=209.9 (21 a) to 412.3 (12 b) kJ mol-1 in which the experimental
      densities are >1.515 g cm-3.

PMID- 16952193
TI  - Validation of QF-PCR for prenatal aneuploidy screening in the United States.
AB  - OBJECTIVE: QF-PCR is an inexpensive and reliable method for aneuploidy screening;
      however, despite its obvious advantages, it is not in routine use in the United
      States. Our objective in the present study was to validate QF-PCR as a means for
      prenatal aneuploidy screening in our institution. METHODS: A QF-PCR assay using
      15 primer pairs located on chromosomes 13, 18, 21 X and Y was established for
      aneuploidy screening. Amniotic fluid (AF) and chorionic villus sampling (CVS)
      samples consisting only of the cells recovered from the plasticware discarded by
      our institutional cytogenetics laboratory were collected and DNA was prepared by
      a simple and inexpensive microwave procedure. QF-PCR was then performed and
      interpreted using established criteria. RESULTS: 687 consecutive prenatal samples
      were screened in a blinded prospective manner, and results were compared to those
      obtained by conventional cytogenetics. 100% of autosomal trisomies were detected,
      and there were zero false positives. A single case each of XXY and 45X were
      missed. CONCLUSIONS: QF-PCR for prenatal aneuploidy screening was validated in
      our laboratory and has now been approved by the New York State Clinical
      Laboratory Evaluation Program. We propose a simple protocol for integrating QF
      PCR into the normal cytogenetics laboratory workflow.

PMID- 16952194
TI  - Validation of DNA probes for preimplantation genetic diagnosis (PGD) by
      fluorescence in situ hybridization (FISH) R1.
AB  - BACKGROUND: Preimplantation genetic diagnosis (PGD) by fluorescence in situ
      hybridization (FISH) is being employed increasingly by medical centers and
      private companies. Validation of any clinical assay, particularly one with novel
      applications such as PGD by FISH, is of critical importance in the clinical
      setting. This importance is recognized by both the College of American
      Pathologists (CAP) and the American College of Medical Genetics (ACMG), who
      recommend validation of FISH assays in the clinical setting. Validation of FISH
      assays for PGD is especially significant, as only one or two cells (blastomeres)
      will be available for testing of a given embryo. METHODS: We have developed
      validation protocols for a variety of FISH assays, including sex identification,
      structural chromosomal aneusomy, and aneuploidy screening with the Vysis, Inc.,
      PGT probe panel. RESULTS: Our validation results show good individual performance
      of commercially available probes, and decreasing overall efficiency as the number
      of probes included in an assay increases.

PMID- 16952195
TI  - Gene therapy for BCR-ABL+ human CML with dual phosphorylation resistant p27Kip1
      and stable RNA interference using an EBV vector.
AB  - BACKGROUND: BCR-ABL-mediated chronic myelogenous leukemia (CML) CD34(+) cell
      proliferation mostly depends on the nucleo-cytoplasmic ratio of the cyclin
      dependent kinase inhibitor p27. The ubiquitin-ligase SCF(Skp2) promotes
      degradation of phosphorylated p27 at T187 in the nucleus, resulting in G1/S
      progression of the cells. On the other hand, phosphatidylinositol-3-kinase (PI3K)
      directed T157 nuclear localization signal (NLS) phosphorylation results in
      cytoplasmic sequestration of p27, leading to abnormal integrin-mediated
      proliferation of CD34(+) CML cells. METHODS: We demonstrate the generation of an
      engineered Epstein-Barr virus (EBV) vector with a BAC backbone that has the
      unique capacity to carry doubly modified (DM) p27 (i.e. T187A, T157A p27) along
      with the BCR-ABL siRNA expression construct. The HSV-tk suicide gene has also
      been incorporated in the same vector, which promotes apoptosis in a BCR-ABL
      independent pathway. RESULTS: Expression of DM p27 markedly inhibits
      proliferation of BCR-ABL(+) primary human CML cells. Moreover, DM p27 strongly
      inhibits the growth of imatinib-resistant CML cells, compared to the T157A p27
      (SM p27). The CML growth inhibition is found to be the result of significant G1/S
      arrest with concomitant increase in hypophosphorylated retinoblastoma (Rb).
      Moreover, the EBV vector mediated stable RNA interference induces apoptosis in
      K562 cells and reduces myeloid colony forming units. CONCLUSIONS: We therefore
      propose a multi-gene delivery strategy for BCR-ABL(+) CML cells by targeting not
      only the fusion transcript, but also the downstream signaling, to overcome drug
      resistance in the acute phase of CML.

PMID- 16952196
TI  - Adenovirus efficiently transduces plasmacytoid dendritic cells resulting in TLR9
      dependent maturation and IFN-alpha production.
AB  - BACKGROUND: Recombinant replication-deficient adenoviral vectors (recAd) are
      attractive candidates for DNA vaccination approaches because they are able to
      activate the innate and adaptive immune systems. Here we explore the ability of
      recAd to transduce and activate subsets of dendritic cells, namely plasmacytoid
      dendritic cells (pDC) and conventional dendritic cells (cDC). METHODS: DC were
      derived from bone marrow precursors in vitro with the help of FLT3-ligand. Sorted
      populations of pDC and cDC were infected with recAd at various multiplicities of
      infection. Transduction efficiency, phenotypic maturation and production of IFN
      alpha as well as IL-6 were assessed. Additionally, activation of DC and induction
      of cytotoxic T lymphocytes (CTL) were determined in vivo. The role of Toll-like
      receptor (TLR) 9 in recAd recognition was investigated as it has previously been
      shown that DNA viruses are recognized via this receptor. RESULTS: RecAd can
      efficiently transduce pDC as well as cDC in vitro. Both DC subsets mature and
      produce IFN-alpha upon interaction with recAd. In the absence of TLR9, activation
      and cytokine production was only detected in cDC but not in pDC. Importantly,
      induction of CD8+ CTL following in vivo injection of recAd was similar in TRL9
      deficient mice when compared with wildtype controls. CONCLUSIONS: RecAd can
      efficiently transduce and activate both pDC and cDC. pDC required TLR9 to detect
      the presence of recAd whereas cDC also recognized recAd independently of TLR9.
      These unique immunostimulatory properties support the future development of
      recombinant Ad as a vector for DNA vaccine approaches.

PMID- 16952197
TI  - Prenatal diagnosis of septal agenesis with normal pituitary function.
AB  - Septal agenesis is a rare brain malformation that is characterized by partial or
      complete absence of the septum pellucidum, either isolated or associated with
      other brain anomalies. We report a case presenting with septal agenesis and
      normal optic chiasm and pituitary function in a fetus at 19 weeks of gestation.

PMID- 16952198
TI  - Quantitative distribution of a panel of circulating mRNA in preeclampsia versus
      controls.
AB  - OBJECTIVE: The aim of this study was to evaluate whether the quantitative
      distribution of a panel of circulating mRNAs from maternal whole blood of normal
      pregnancies is statistically different from those complicated with preeclampsia
      (PE) with or without intrauterine growth restriction (IUGR). METHODS: Maternal
      whole blood of six subjects with mild or severe PE with or without IUGR and 30
      matched controls (1:5 match for gestational age) were retrospectively examined
      for circulating mRNA markers. Seven specific mRNA markers were identified and
      chosen based on previous microarray mRNA expressions performed on placental
      tissue from normal and PE patients. They were human placental lactogen (hPL),
      inhibin A, KISS-1, pregnancy-associated plasma protein-A (PAPP-A), plasminogen
      activator inhibitor type 1 (PAI-1), selectin-P and vascular endothelial growth
      factor receptor (VEGFR), which were therefore quantified for statistical
      purposes. RESULTS: Median gestational age was 229 (178-283) and 232 (194-262)
      days for controls and cases respectively. All mRNA markers but PAPP-A, showed
      statistically different median values. They were hPL, inhibin A, KISS-1, PAI-1,
      Selectin-P, and VEGFR. Inhibin A, Selectin-P and VEGFR showed higher values than
      expected for controls. Instead, hPL, KISS-1 and PAI-1 values of PE patients were
      lower than those of controls. Selectin-P was the marker with the most aberrant
      difference, followed by VEGFR and KISS-1. CONCLUSION: This preliminary analysis
      revealed that the median values of a panel of mRNAs from the maternal blood of PE
      patients were different from those of the same gestational age control group at
      the third trimester. If prospective studies at the second trimester could detect
      a related marker sufficiently able to discriminate between affected and
      unaffected patients and thus detect the disease before its clinical onset, then a
      screening project using a panel of mRNAs would be feasible.

PMID- 16952199
TI  - Metformin prolongs the postprandial fall in plasma ghrelin concentrations in type
      2 diabetes.
AB  - BACKGROUND: Weight loss is difficult to achieve in type 2 diabetes and many
      therapies are associated with weight gain, an effect attenuated by metformin. We
      studied the effects of metformin on energy expenditure, appetite and the
      regulation of PYY and ghrelin in type 2 diabetes. METHODS: Plasma peptide YY
      (PYY), ghrelin, resting metabolic rate (RMR), postprandial thermogenesis (PPTG),
      and appetite ratings were measured at baseline and following a mixed meal in 11
      type 2 diabetic subjects treated with diet alone (T2D) and 10 treated with
      metformin monotherapy (T2MF). The groups were similar in age, gender and
      adiposity. RESULTS: There were no differences in baseline anthropometric, or
      metabolic variables between the groups. Postprandially, plasma ghrelin fell
      equally in both groups (23% versus 24.5%, p < 0.05 versus baseline, p = NS
      between groups) but were reduced for longer in T2MF (below baseline 60-240 min
      T2MF versus 60-180 min T2D) coincidentally with a prolonged sensation of fullness
      and suppression of hunger in the metformin-treated group. There were no
      differences in PYY concentrations, RMR or PPTG. CONCLUSIONS: Metformin prolongs
      the postprandial fall in ghrelin concentrations. These effects may prolong the
      inter-meal interval, thereby decreasing snack intake and daily energy intake,
      promoting weight loss.

PMID- 16952200
TI  - Pharmacogenomics of cancer chemopreventive isothiocyanate compound sulforaphane
      in the intestinal polyps of ApcMin/+ mice.
AB  - Sulforaphane (SFN) is an isothiocyanate that is present in widely consumed
      vegetables. Previous studies have shown that SFN is effective in preventing
      carcinogenesis induced by carcinogens in rodents. Recently it was found that SFN
      could also suppress the growth of intestinal polyps in the ApcMin/+ mouse. In the
      present study, the acute effect of SFN on the gene expression profile in small
      intestinal polyps of ApcMin/+ mice using Affymetrix microarray was performed. SFN
      is a strong inducer for phase II drug metabolizing enzymes, which is believed to
      contribute to its chemopreventive properties. However, the results show that
      genes involved in apoptosis, cell growth and maintenance rather than the
      predicted phase II genes were modulated. The proapoptotic genes including MBD4,
      TNFR-7 and TNF (ligand)-11 were up-regulated while pro-survival genes including
      cyclin-D2, integrin-beta1 and Wnt-9A were down-regulated. Interestingly, two
      genes potentially involved in colorectal carcinogenesis, 15-LOX and COX-2 were
      found to be increased and decreased, respectively. In conclusion, the results
      show, for the first time, that chemopreventive agents such as SFN regulate
      different set of genes involving apoptosis, cell growth/maintenance and
      inflammation in the small intestinal polyps of ApcMin/+ mice, which could
      contribute to the overall chemopreventive pharmacological effects.

PMID- 16952201
TI  - Plasma interleukin-6 levels are increased in subjects with impaired glucose
      tolerance but not in those with impaired fasting glucose in a cohort of Italian
      Caucasians.
AB  - BACKGROUND: While the relationship between impaired glucose tolerance (IGT) and
      circulating interleukin-6 (IL-6) is well established, there is no information
      whether IL-6 levels are elevated in impaired fasting glucose (IFG). METHODS: To
      this end, we examined the relationship between plasma IL-6 concentration and
      different degrees of glucose homeostasis in a cohort of 470 Italian Caucasian
      subjects comprising 236 normal glucose tolerant (NGT), 49 IFG, 51 IGT, and 134
      type 2 diabetic subjects. RESULTS: We observed that IL-6, CRP and fibrinogen
      levels were higher in subjects with IGT or type 2 diabetes as compared with NGT
      and IFG subjects. Univariate correlations between IL-6 concentrations and
      metabolic variables in the whole cohort showed that IL-6 levels were positively
      correlated with age, BMI, waist, systolic and diastolic blood pressure, fasting
      plasma glucose, triglycerides, CRP, fibrinogen, and negatively correlated with
      insulin sensitivity, IGF-I and HDL. In a subgroup analysis including NGT, IFG and
      IGT (n = 336), IL-6 levels were positively correlated with age, BMI, waist,
      systolic and diastolic blood pressure, triglycerides, CRP, fibrinogen, fasting
      insulin, 2 h post-load glucose, and negatively correlated with insulin
      sensitivity, IGF-I and HDL. Stepwise linear regression analysis in a model
      including gender, age, BMI, waist, glucose tolerance status, fasting plasma
      glucose, 2 h post-load glucose, triglycerides, HDL, fasting insulin, and insulin
      sensitivity revealed that waist was the only independent variable associated with
      IL-6 levels accounting for 21.0% of its variation (P < 0.0001). CONCLUSIONS:
      These data show that IGT and type 2 diabetes, but not IFG, are associated with
      elevated plasma IL-6 levels.

PMID- 16952203
TI  - Prenatal sonographic diagnosis of congenital perineal skin tag: case report and
      review of the literature.
AB  - BACKGROUND: Skin tags, or acrochordons, are benign, soft, fleshy tumors that are
      composed of hyperplastic epidermis covering a dermal connective tissue stalk.
      METHODS: Case report of a congenital perineal skin tag that presented as a
      perineal tumor during second-trimester sonographic scan at 23 weeks' gestation.
      Literature review of the medical literature using Pubmed(R) and the search terms
      acrochordon, fibroepithelial polyp (FEP), and skin tag. RESULTS: Routine
      midtrimester targeted organ scanning at 23 weeks' gestation revealed a 5-mm
      hypoechogenic elongated mass in the perineal area of the fetus. The lesion
      progressed to twice that size by 36 weeks. Detailed anatomy scan of the fetus was
      unremarkable, and amniocentesis demonstrated normal karyotype. The mother
      developed spontaneous labor at 38 weeks' gestation and delivered a phenotypically
      normal girl with a round smooth mass in the perineal area. The lesion was
      removed; pathologic examination revealed a lipomatous skin tag. Literature review
      showed skin tags associated with different medical conditions. CONCLUSION: To the
      best of our knowledge, no prenatally diagnosed cases of this lesion on the fetal
      perineum have been published. In the present case, this was an innocuous finding.

PMID- 16952202
TI  - Gliclazide protects human islet beta-cells from apoptosis induced by intermittent
      high glucose.
AB  - BACKGROUND: Decreased beta-cell mass, mainly due to apoptosis, is crucial for the
      development and progression of type 2 diabetes. Chronic exposure to high glucose
      levels is a probable underlying mechanism, whereas the role of oral anti-diabetic
      agents (sulphonylureas in particular) is still unsettled. METHODS: To directly
      investigate more on such issues, we prepared isolated human islets, which were
      then cultured for 5 days in continuous normal glucose concentration (NG, 5.5
      mmol/L) or normal and high (HG, 16.7 mmol/L) glucose levels (alternating every 24
      h), with or without the addition of therapeutical concentration (10 micromol L)
      of gliclazide or glibenclamide. RESULTS: Intermittent high glucose caused a
      significant decrease of glucose-stimulated insulin secretion, which was not
      further affected by either sulphonylurea. Apoptosis, as assessed by electron
      microscopy, was also significantly increased by alternating high glucose
      exposure, which was accompanied by altered mitochondria morphology and density
      volume, and increased concentrations of nitrotyrosine, a marker of oxidative
      stress. Gliclazide, but not glibenclamide, was able to significantly reduce high
      glucose induced apoptosis, mitochondrial alterations, and nitrotyrosine
      concentration increase. CONCLUSION: Therefore, gliclazide protected human beta
      cells from apoptosis induced by intermittent high glucose, and this effect was
      likely to be due, at least in part, to the anti-oxidant properties of the
      molecule.

PMID- 16952204
TI  - Prenatal ultrasonographic prediction of the umbilical coiling index at birth and
      adverse pregnancy outcome.
AB  - OBJECTIVES: To evaluate whether the antenatal umbilical coiling index (aUCI) as
      measured by ultrasonography predicts the postnatal umbilical coiling index (pUCI)
      and adverse pregnancy outcome. METHODS: In a prospective study in 117
      pregnancies, the aUCI was measured between 28 weeks and term by ultrasonography.
      The aUCI was calculated as the reciprocal value of the mean pitch of one complete
      coil. The pUCI was calculated as the number of coils divided by the cord length
      in cm. The correlation between aUCI and pUCI was assessed and likelihood ratios
      for adverse pregnancy outcome were calculated. RESULTS: We had complete data on
      81 subjects. Mean aUCI +/- SD was 0.30 +/- 0.09 and mean pUCI +/- SD was 0.17 +/-
      0.08. The correlation coefficient between aUCI and pUCI was 0.66, P < 0.001.
      Limits of agreement were 0-0.28 coils/cm. The positive likelihood ratio for small
      for-gestational-age infants was 2.6 (95% confidence interval (CI) 0.6-11.6) for
      ultrasound hypocoiling, and 5.7 (95% CI 1.3-24.8) for ultrasound hypercoiling.
      The positive likelihood ratio for interventional delivery for non-reassuring
      fetal status was 1.2 (95% CI 0.2-9.0) for ultrasound hypocoiling, and 10.3 (95%
      CI 2.1-50.2) for ultrasound hypercoiling. CONCLUSIONS: Strong correlation
      coefficients comparing the aUCI and pUCI do not reflect agreement. Since the
      limits of agreement were almost as wide as the full range for the pUCI, the aUCI
      does not predict the pUCI with sufficient precision. Larger prospective studies
      are required to confirm the predictive potential of the aUCI for adverse
      pregnancy outcome.

PMID- 16952205
TI  - Cognitive testing in early phase clinical trials: outcome according to adverse
      event profile in a Phase I study.
AB  - BACKGROUND: It has been proposed that objective cognitive testing provides
      additional information to that collected via adverse event (AE) recordings.
      However, in clinical trials of compounds with potentially negative effects on
      cognition, the results of cognitive testing may overlap with AE recordings. AIMS:
      To examine cognitive function in subjects who do and do not report sedation
      related AEs in a Phase I clinical trial. METHODS: Five computerized cognitive
      tasks were administered to 28 healthy male volunteers enrolled in a simulated
      Phase I study using midazolam to induce sedation-related AEs and cognitive
      dysfunction. For each subject, the magnitude of cognitive change between pre-dose
      and 1 hr post-dose assessments was calculated. Group and individual level
      cognitive outcome was compared between subjects who did and did not report
      sedation-related AEs following administration of 1.75 and 5.25 mg midazolam.
      RESULTS: At both doses of midazolam, cognitive dysfunction was observed in both
      subject groups (i.e., those who did and did not report AEs). Analysis of
      individual outcomes identified consistent cognitive dysfunction among subjects
      who reported sedation-related AEs. Further, in the 5.25 mg condition a subset of
      individuals (66.7%) who did not report sedation-related AEs nevertheless
      displayed substantial cognitive dysfunction. CONCLUSIONS: Following
      administration of oral midazolam, there is a dissociation between sedation
      related AE recordings and performance on computerized cognitive tests of motor
      function, attention, strategy use and problem solving, learning and delayed
      recall. Inclusion of computerized cognitive tests in early phase trials may allow
      identification of subtle cognitive change, beyond that which is possible by self
      report and clinical observation.

PMID- 16952206
TI  - Surgery for hepatocellular carcinoma in patients with chronic liver disease.

PMID- 16952207
TI  - Increased angiogenic response but deficient arteriolization and abnormal
      microvessel ultrastructure in critical leg ischaemia.
AB  - BACKGROUND: Ischaemia is known to induce angiogenesis, but the effects of
      critical leg ischaemia (CLI) on angiogenesis remain unclear. The aim of this
      study was to examine the physiological angiogenic response in CLI by
      investigating the extent of neovascularization, characterizing microvessel
      subtypes and determining the microvessel ultrastructure. METHODS: Gastrocnemius
      muscles were biopsied from 12 patients with CLI and 12 without leg ischaemia.
      Microvessels were evaluated immunohistochemically using three endothelial markers
      (anti-CD31, anti-CD34 and PAL-E) and anti-alpha smooth muscle actin (SMA) as a
      mural cell marker to label arterioles. Ki67 was used to demonstrate active cell
      proliferation. Further microvessel ultrastructural characteristics were
      determined by transmission electron microscopy. RESULTS: The CLI group had
      significantly higher microvessel density and microvessel : muscle fibre ratio for
      all endothelial subtypes examined (P < 0.001). PAL-E staining demonstrated the
      highest increase: 4.7 times higher in CLI muscle. There was no significant
      difference in alphaSMA-positive microvessel density (P = 0.118) or microvessel:
      muscle fibre ratio (P = 0.214). Ki67 staining showed no active cell
      proliferation. Transmission electron microscopy showed CLI microvessels had
      abnormal morphology, mainly a thick basement membrane. CONCLUSION: A
      physiological angiogenic response was found in CLI, but the microvessels had an
      abnormal ultrastructure. A lack of active cell proliferation suggests that the
      angiogenic response may have been exhausted.

PMID- 16952208
TI  - A 10-year review of surgery for desmoid disease associated with familial
      adenomatous polyposis.
AB  - BACKGROUND: Desmoid tumours affect 10-25 per cent of patients with familial
      adenomatous polyposis and represent a major cause of morbidity and mortality.
      Surgery for intra-abdominal desmoids has traditionally been used as a last resort
      or to manage obstructive complications. The aim was to review 10 years of desmoid
      surgery in patients with familial adenomatous polyposis from a single centre.
      METHODS: Patients who had surgery for desmoid disease between 1994 and 2004 were
      identified from the Polyposis Registry database and their hospital notes
      reviewed. RESULTS: Twenty patients had surgery to remove 32 desmoid tumours (16
      intra-abdominal, 12 abdominal wall, four extra-abdominal). Complete clearance was
      achieved in 19 tumours and, of these, clinically significant recurrence occurred
      in eight. There was no difference in recurrence rates for site or sex. There was
      no operative mortality. Intra-abdominal desmoid resection was associated with a
      mean resection of 45.55 (range 10-200) cm of small bowel. One patient required
      long-term parenteral feeding. Median follow-up was 5 (range 0.6-10) years. During
      this period, one patient died (metastatic duodenal cancer); there was no
      mortality from desmoid disease. CONCLUSION: Surgery for intra-abdominal desmoids
      in selected patients is less hazardous than previously reported. Surgery for
      abdominal wall and extra-abdominal tumours is safe. However, disease recurrence
      remains a major problem.

PMID- 16952209
TI  - Randomized clinical trial of local gentamicin-collagen treatment in advancement
      flap repair for anal fistula.
AB  - BACKGROUND: Endoanal advancement flap repair is widely used in sphincter
      preserving surgery for anal fistula, but the high recurrence rate is a major
      problem. A possible cause of non-healing is local infection of the flap. The aim
      of this study was to evaluate whether local antibiotic treatment with gentamicin
      collagen improves healing after endoanal advancement flap repair for anal
      fistula. METHODS: Eighty-three patients (52 men and 31 women; mean age 47 (range
      17-71) years) who had endoanal advancement flap repair for anal fistula between
      September 1998 and January 2004 were randomized to surgery with (42 patients) or
      without (41 patients) application of gentamicin-collagen beneath the flap.
      Patients were evaluated at 1-3 and 12 months after surgery for healing and/or
      recurrence. RESULTS: The overall healing rate with no recurrence at 1 year after
      surgery was 57 per cent (47 of 83). Twenty-six of 42 patients randomized to
      gentamicin-collagen healed primarily compared with 21 of 41 patients randomized
      to surgery only. There were no overall differences in healing rate according to
      sex, previous fistula surgery, complexity of fistula, smoking habit or body mass
      index. CONCLUSION: Endoanal advancement flap repair for anal fistula has a fairly
      high primary recurrence rate. Healing was not significantly improved by local
      application of gentamicin-collagen.

PMID- 16952210
TI  - Outcome of antegrade continence enema procedures for faecal incontinence in
      adults.
AB  - BACKGROUND: Faecal incontinence has major consequences. Colostomy has been the
      mainstay of therapy when other options fail. Operations such as the Malone
      procedure have been proposed as an alternative. The aim of this study was to
      evaluate the outcomes and quality of life of patients having a Malone procedure
      for the treatment of faecal incontinence. METHODS: Charts of patients who had had
      a Malone procedure or equivalent between 1998 and 2004 were reviewed. The
      patients completed a Short Form (SF) 36 quality of life questionnaire. RESULTS:
      The study included 25 patients (17 female; median age 47 years). In seven, the
      appendix was used; an ileoneoappendicostomy was performed in the other 18. Three
      patients were lost to follow-up; the remaining 22 were followed for a median
      (range) of 21 (1-61) months. Five patients had a cutaneous stenosis; another had
      the appendicostomy removed and replaced by a colostomy. Four patients no longer
      used the stoma for irrigation. All other patients were completely clean except
      one, who reported occasional night-time seepage. The mean SF-36 showed a good
      physical recovery (43.9) but persisting psychological distress (36.0).
      CONCLUSION: The Malone procedure or equivalent achieves good results in the
      management of faecal incontinence, although psychological distress persists after
      surgery.

PMID- 16952211
TI  - Simultaneous quantitative analysis of the antimalarials pyrimethamine and
      sulfamethoxypyrazine in plasma samples using liquid chromatography/tandem mass
      spectrometry.
AB  - The work presented here deals with the development of a quantitative tool for the
      simultaneous determination of sulfamethoxypyrazine (sulfalene)/pyrimethamine in
      plasma. The chromatography used only takes 12.5 min, allowing a fast sample
      turnover time. Relative standard deviation of retention times was never above
      3.48% (n = 66). Adequate sample clean-up was achieved by a simple and relatively
      fast liquid/liquid extraction. In this way, ionisation suppression effects,
      typical for more simple sample clean-up procedures, could be avoided resulting in
      absolute plasma effects of maximum -17.1% for sulfalene, -16.1 for the internal
      standard (IS), and 12% for pyrimethamine. For both pyrimethamine and sulfalene,
      quadratic calibration curves from 0.00101 to 0.807 microg/mL for pyrimethamine
      and from 0.271 to 216 microg/mL for sulfalene gave the best fit. Mean
      coefficients of determination (R2) were 0.9951 (n = 6, CV% 0.39) for
      pyrimethamine and 0.9942 (n = 6, CV% 0.13) for sulfalene. Precision was below
      9.35% for pyrimethamine and 13.9% for sulfalene. Inaccuracy remained below 15% at
      all cases. The optimised method was used for a time-course study of the
      sulfalene/pyrimethamine combination concentration in plasma of patients treated
      with Co-Arinate, a new curative antimalaria-medicine.

PMID- 16952212
TI  - Reduction of nitriles to amines in positive ion electrospray ionization mass
      spectrometry.
AB  - Some compounds readily form [M+46]+ adduct ions during positive ion electrospray
      ionization mass spectrometry ((+)ESI-MS) analysis. These [M+46]+ ions were
      characterized as [M+CH3CH2NH2+H]+ by accurate mass determination. Ethylamine
      involved in the adduct was proposed to be the reduction product of acetonitrile
      and this was confirmed using deuterated acetonitrile. Other nitrile-containing
      compounds tested, including isobutyronitrile and benzonitrile, also formed the
      adduct ions of the respective amine forms under (+)ESI-MS conditions.
      Hydrogen/deuterium exchange experiments demonstrated that the reductive hydrogen
      originated from water. Reduction of nitriles (R-CN) to their respective amines (R
      CH2NH2) under (+)ESI-MS conditions expands the ability to identify nitrile
      containing chemical unknowns.

PMID- 16952213
TI  - Randomized clinical trial of the effects on anal function of Milligan-Morgan
      versus Ferguson haemorrhoidectomy.
AB  - BACKGROUND: Studies of haemorrhoidectomy usually report postoperative pain,
      healing and complications, but rarely consider anal function in the longer term.
      The primary aim of this randomized trial was to compare long-term changes in anal
      function after open (Milligan-Morgan) and closed (Ferguson) haemorrhoidectomy.
      METHODS: A total of 225 patients were included in the trial, 115 in the open
      group and 110 in the closed group. Continence changes were recorded by means of
      validated questions and an incontinence score. Pain was self-reported using a
      visual analogue scale. RESULTS: Postoperative pain and complications did not
      differ between the groups. Time to recovery was 17 days in the Milligan-Morgan
      group and 15 days in the Ferguson group. After 1 month the wounds were healed in
      57.0 per cent of patients in the open group and 70.6 per cent of those in the
      closed group (P = 0.058). At 1 year, 78.9 per cent of the Milligan-Morgan group
      and 85.3 per cent of the Ferguson group reported no continence disturbance (P =
      0.072). The incontinence score was improved at 1 year in the closed group (P =
      0.015), but was unchanged in the open group (P = 0.645). Patients who had the
      Ferguson procedure were more satisfied with the outcome of surgery (P = 0.047).
      CONCLUSION: Closed Ferguson haemorrhoidectomy was superior to the open Milligan
      Morgan procedure with respect to long-term anal continence and patient
      satisfaction.

PMID- 16952214
TI  - First-trimester ultrasound and biochemical markers of aneuploidy and the
      prediction of impending fetal death.
AB  - OBJECTIVES: To examine the clinical utility of the first-trimester markers of
      aneuploidy in their ability to predict future fetal loss. METHODS: We examined
      54,722 singleton pregnancies with no chromosomal abnormality and with complete
      outcome data that had undergone screening for trisomy 21 by a combination of
      fetal nuchal translucency (NT) thickness, maternal serum free beta-human
      chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP
      A) at 11 + 0 and 13 + 6 weeks' gestation. The biochemical markers were converted
      to multiples of the expected normal median for a pregnancy of the same gestation
      (MoM) and the measurements of fetal NT were expressed as the difference (delta)
      from the normal median NT for crown-rump length (CRL). The association between
      free beta-hCG, PAPP-A and delta NT and the incidence of fetal loss prior to 24
      weeks, at or after 24 weeks or at any time, was assessed by comparing the
      relative incidence at a number of MoM or delta NT cut-offs and at various centile
      cut-offs. At various marker levels the likelihood ratio (LR) for fetal loss was
      also calculated. RESULTS: The rate of fetal loss increased with decreasing
      maternal serum free beta-hCG and PAPP-A and increasing delta NT. At the 5th
      centile of the normal outcome group for free beta-hCG (0.41 MoM) the odds ratio
      for fetal loss before 24 weeks, at or above 24 weeks and at any gestation was
      3.1, 1.8 and 2.6, respectively. The respective values for the 5th centile of PAPP
      A (0.415 MoM) were 3.3, 1.9 and 2.8 and for the 95th centile of delta NT they
      were 2.5, 1.9 and 2.2, respectively. There was almost no correlation between
      reduced levels (<or=0.50 MoM) of PAPP-A and reduced levels of free beta-hCG in
      either the normal pregnancy group (r = 0.041) or the group with fetal death (r =
      0.072), indicating relatively independent prediction by either biochemical
      marker. CONCLUSIONS: Low levels of maternal serum PAPP-A and free beta-hCG and
      increased fetal NT are associated, in the absence of an abnormal karyotype, with
      an increased risk of impending fetal death. The likelihood ratio profiles
      provided at various levels of PAPP-A or free beta-hCG may be of some help in
      counseling women with such results and raise awareness among health-care
      professionals for increased surveillance in such cases.

PMID- 16952215
TI  - Direct determination of estriol conjugates in amniotic fluid by capillary
      electrophoresis with electrospray tandem mass spectrometry.

PMID- 16952216
TI  - Determining chorionicity in twin gestations: three-dimensional (3D) multiplanar
      sonographic measurement of intra-amniotic membrane thickness.
AB  - OBJECTIVES: Measuring the thickness of the membranes to determine chorionicity in
      twins using two-dimensional (2D) ultrasound may provide uncertain results, given
      the possibility of measuring in an oblique view. We aimed to determine whether
      chorionicity can be assessed during the second and third trimesters by measuring
      the thickness of the membranes with three-dimensional (3D) multiplanar
      ultrasound, which ensures the measurement is perpendicular to the membranes, and
      to evaluate the reproducibility of the technique. METHODS: This was a prospective
      study of 84 twin pregnancies (30 monochorionic and 54 dichorionic) between 20 and
      35 weeks of gestation. The dividing membranes between the fetuses were visualized
      with 2D and 3D transabdominal sonography and the thickness of the membranes was
      measured by the multiplanar technique. Intraobserver variability was assessed by
      comparing the measurements obtained in sagittal and axial views by the same
      observer. We examined the frequency distributions to determine the optimal cut
      off point of the thickness of the membranes to predict chorionicity. Kappa index,
      intraclass correlation coefficients and 95% limits of agreement were calculated
      to evaluate the inter- and intraoperator variability. We also compared membrane
      thickness measurement, during the second and third trimesters, using 2D and 3D
      ultrasound. RESULTS: In monochorionic and dichorionic pregnancies, respectively,
      the mean thickness was 1.42 (SD, 0.31) mm and 2.48 (SD, 0.47) mm. With 3D
      ultrasound, the intraclass correlation coefficient was 0.99 in all cases. The 95%
      limits of agreement were all within +/-0.2 mm. The best cut-off for membrane
      thickness for discriminating monochorionic from dichorionic twinning was 1.8 mm.
      Using this cut-off, there were one false-negative (sensitivity, 97%; 95% CI, 83
      99%) and three false-positive (specificity, 94%; 95% CI, 85-99%) diagnoses of
      monochorionic twins. Kappa indices for intra- and interoperator variability were
      all above 90%, suggesting almost perfect agreement. Measurements with 2D
      sonography were less accurate (sensitivity and specificity, 83%). CONCLUSION:
      Prenatal assessment of dividing membranes using 3D multiplanar ultrasound is
      reproducible and may be a useful alternative method for determining chorionicity
      in twin pregnancies during the second and third trimesters.

PMID- 16952217
TI  - Mass spectral differentiation of diastereomeric hydroxybrevicomins by electron
      ionization.

PMID- 16952218
TI  - Interpretive flexibility: why doesn't insight incite controversy in mental health
      law?
AB  - This research investigates how the term "insight" was employed in 25 decisions
      from mental health review proceedings in Victoria, Australia. The application of
      insight appears problematic in these decisions. First, there is little
      clarification of its meaning. Second, the logic applied when insight is related
      to compliance is often unclear. Third, there are frequent allusions to an
      implicit and undefined scale of insight, offering the appearance of objectivity.
      We have analysed insight as an 'interpretive resource', focusing on its various
      functions in the complex social context of commitment hearings and with a view to
      its therapeutic jurisprudence implications. The variable application of insight
      its interpretive flexibility-appears useful in addressing complex problems faced
      by review boards. Hence, a key function of insight is to bridge between legal and
      clinical discourses. Insight is also a convenient means to avoid complicated
      debates regarding the person's credibility. By analysing insight in Victoria, we
      hope to contribute to better theoretical understanding of decision-making
      patterns in mental health law in general.

PMID- 16952219
TI  - Relationships between personal values and reported behavior on ethical scenarios
      for law students.
AB  - Lawyers' values might be considered to play some role in the decisions that are
      made in everyday legal practice. This study aimed to explore the effects of
      personal value hierarchies on ethical decision making within the context of
      several ethical dilemmas. A questionnaire was administered utilizing hypothetical
      situations presented in 11 ethical scenarios and including the Rokeach Value
      Survey. Logistic regression results suggested that different personal values were
      significant predictors of reported behavioral choices on respective ethical
      scenarios. However, the most important values associated with behavior consistent
      with ethical conduct in scenarios were 'honesty' and 'equality'. The implications
      of results are discussed in the contexts of ethics education in a tertiary
      educational environment and in relation to regulation for the professions.

PMID- 16952221
TI  - [Emancipation of children].

PMID- 16952220
TI  - Antioxidative and in vitro hepatoprotective activity of Bupleurum kaoi leaf
      infusion.
AB  - The roots of Bupleurus spp. have been used in traditional Chinese herbal medicine
      for curing liver diseases. Although bioactive saikosaponins have been detected in
      the leaves as well as in the roots, the aerial parts of the plants are discarded
      as waste. In the present study, a leaf infusion of B. kaoi Liu, Chao et Chuang,
      an indigenous Bupleurus species in Taiwan, was prepared and the antioxidant
      properties and in vitro hepatoprotective activity were demonstrated. The results
      show that the leaf infusion exerted DPPH free radical scavenging activity,
      inhibitory capacity on superoxide anion formation and superoxide anion scavenging
      activity. The hepatotoxicity of acetaminophen (APAP) and carbon tetrachloride
      (CCl4) on the rat liver cells were also decreased by the leaf infusion.

PMID- 16952222
TI  - [Meetings of the Pediatric Section of the French Society of Cardiology].

PMID- 16952224
TI  - Controlled self-assembly of triphenylene-based molecular nanostructures.
AB  - Molecular nanostructures of the disc-shaped molecule hexapentyloxytriphenylene
      have been fabricated on length scales ranging from 30 nm to 1.5 mum following
      self-assembly arising from pi-pi interactions in organic solvents. The size and
      density of the molecular nanostructures deposited onto glass and indium tin oxide
      coated glass substrates were characterized by atomic force microscopy. Dynamic
      light scattering and spectroscopic evidence of predeposition aggregation in
      solution are presented, suggesting that the nanostructures are organized in
      solution and then deposited onto the substrate. Correlations between the relative
      solvent polarity and the size of molecular nanostructures as well as between the
      solute concentration in dilute solutions and their density on the substrate are
      discussed.

PMID- 16952223
TI  - Controllable preparation of monodisperse O/W and W/O emulsions in the same
      microfluidic device.
AB  - This letter presents a simple way to prepare monodisperse O/W and W/O emulsions
      in the same T-junction microfluidic device just by changing the wetting
      properties of the microchannel wall with different surfactants. Highly uniform
      droplets ranging from 50 to 400 mum with a polydispersity index (sigma) value of
      less than 2% were successfully prepared. With the change in surfactants and
      surfactant concentrations, the interfacial tension and the wetting properties
      varied, and disordered or ordered two-phase flow patterns could be controllable.
      Monodisperse O/W and W/O emulsions were prepared under the action of a cross
      flowing shear force or a perpendicular shear force by using an oil solution with
      0.1-2.0 wt % Span 80 and an aqueous solution with 0.1-2.0 wt % Tween 20 as a
      continuous-phase flow, respectively. It gives a controllable method of preparing
      O/W and W/O emulsions in the same microfluidic device.

PMID- 16952225
TI  - Self-assembled monolayers of dipolar nonlinear optical nickel(II) molecules on
      the Si(100) surface with nanoscale uniformity.
AB  - The synthesis and structure of a dipolar nonlinear optical
      bis(salicylaldiminato)Ni(II)-derivatized Schiff base complex chemisorbed on H
      terminated Si(100) surfaces is reported. The existence of a monolayer of the
      derivatized complex chemisorbed on the Si(100) surface is unambiguously confirmed
      by high-resolution core-level XPS and AFM/SNOM analyses. The comparison between
      the optical SNOM images highlights the contribution of the monolayer to the local
      reflectivity of the sample. Angle-resolved XPS data indicate the presence of
      chlorine head atoms on the monolayer surface. Altogether, XPS and AFM/SNOM data
      suggest the formation of a nanoscale uniform, homogeneous, complete, ordered
      monolayer self-assembled on the Si(100) surface.

PMID- 16952226
TI  - Direct catalytic route to superhydrophobic polyethylene films.
AB  - Polyethylene films grow on a flat silica surface modified by the
      bis(imino)pyridyl iron(II) catalyst during ethylene polymerization in toluene
      solvent. The resulting films show superhydrophobic properties. Advancing water
      contact angle as high as 169 degrees and sliding angles as low as 2 degrees are
      obtained on these films. SEM images reveal special surface structures of these
      films containing micrometer-sized islands, submicrometer particles on the
      islands, and stress nanofibers between the islands, which render
      superhydrophobicity to the polyethylene surfaces. After the submicrometer
      particles and stress nanofibers are removed by annealing, the superhydrophobic
      properties of the polymer films disappear.

PMID- 16952227
TI  - Block copolymer film with sponge-like nanoporous strucutre for antireflection
      coating.
AB  - We prepared nanoporous films by spin-coating of polystyrene-block-poly(methyl
      methacrylate) copolymers (PS-b-PMMA) to a glass and irradiating by ultra-violet
      source followed by selective removal of PMMA blocks with acetic acid. When spin
      coated PS-b-PMMA was no longer annealed at high temperatures, microphase
      separation between two blocks occurred only in the short-range scale. The porous
      films prepared from PS-b-PMMA with the volume fraction of PMMA block of 0.69
      exhibited a spongelike nanoporous structure over the entire film thickness and
      showed excellent antireflection with a minimum reflection less than 0.1% at
      visible and near-infrared wavelengths. The observed reflectances were in good
      agreement with the predictions based on the characteristic matrix theory.

PMID- 16952228
TI  - Effect of binding of an oligomeric cationic fluorosurfactant on the dilational
      rheological properties of gelatin adsorbed at the air-water interface.
AB  - The effect of binding of an oligomeric cationic fluorooxetane surfactant on the
      interfacial properties of adsorbed gelatin-fluorooxetane complexes has been
      studied using dynamic surface tension and dilational rheological measurements.
      Adsorption kinetics of gelatin-fluorooxetane complexes are reminiscent of a mixed
      (barrier/diffusion limited) process, while the dilational rheological properties
      of the interface exhibit a strong dependence on surfactant concentration. At low
      surfactant concentrations, dilational surface moduli as well as phase angles are
      relatively insensitive to the presence of the fluorooxetane. However, at the
      critical aggregation concentration of the polymer-surfactant system, there is a
      sharp increase in the complex modulus. Further increase in the fluorooxetane
      concentration does not significantly affect the complex modulus. The phase angle,
      however, does increase with increasing fluorooxetane concentration due to the
      transport of bound fluorooxetane from the subsurface to the solution-air
      interface. These results indicate that, at fluorooxetane concentrations exceeding
      the critical aggregation concentration, the polymer-surfactant complexes adsorb
      to form cross-linked multilayers at the solution-air interface.

PMID- 16952229
TI  - Mixed adsorption of fluorinated and hydrogenated surfactants.
AB  - The adsorption isotherms of sodium perfluorooctanoate and sodium decyl sulfate
      and their 1:1 mixture on gamma-alumina are recorded by depletion-type experiments
      with (1)H and (19)F NMR spectroscopy as the detection tool. The isotherms of the
      different surfactant species, obtained with and without added salt, closely
      resemble each other. Salt addition changes the isotherms from stepwise to the
      familiar S-shaped. After having reached saturation, a further increase of
      surfactant concentration in the mixed system leads to decyl sulfate desorption
      and increased perfluorooctanoate adsorption. The (19)F chemical shift of adsorbed
      perfluorooctanoate suggests that, for saturated surfaces, the two sorts of
      adsorbed surfactants form molecularly mixed surface aggregates.

PMID- 16952230
TI  - Circular dichroism of optically active poly(dialkylsilane) aggregates in
      microcapsules.
AB  - Poly[n-hexyl-(S)-3-methylpentylsilane] aggregates confined in microcapsules to
      keep the aggregation number and ranging in average polymer mass m(p) in a
      microcapsule from 2 x 10(-)(16) to 2 x 10(-)(14) g were studied by circular
      dichroism measurements in ethanol (a nonsolvent) and tetrahydrofuran (an
      associative solvent at low temperature) at various temperatures. The weight
      average molecular weight M(w) and the polydispersity index (the ratio of M(w) to
      the number-average molecular weight) of the polysilane sample were 6.6 x 10(4)
      and 1.07, respectively, and the average number of polymer molecules in each
      capsule was estimated to be 1.9 x 10(3) for m(p) = 2 x 10(-)(16) g and 1.7 x
      10(5) for m(p) = 2 x 10(-)(14) g. The size of each aggregate did not affect the
      optical activity because the circular dichroism thus obtained was proportional to
      m(p) under the same conditions in the investigated m(p) range; on the other hand,
      the peak height of the circular dichroism in tetrahydrofuran had a significant
      hysteresis between 0 and 25 degrees C. Moreover, the circular dichroism
      appreciably reflected the prepared method, that is, the temperature and solvent;
      in other words, the aggregates memorized the initial conditions in their stacking
      structures.

PMID- 16952231
TI  - Foam films stabilized with dodecyl maltoside. 2. Film stability and gas
      permeability.
AB  - The gas permeability and stability of foam films stabilized by n-dodecyl-beta-D
      maltoside (beta-C(12)G(2)) were determined. The permeability coefficient (K,
      cm/s) and the mean film lifetime were measured as a function of the surfactant
      concentration. The films are less permeable than those stabilized by other
      surfactants at comparable conditions. The permeability coefficient decreases with
      increasing surfactant concentration. It does not show a remarkable dependence on
      the salt concentration. Stable Newton black foam films (NBFs) are formed above a
      surfactant concentration of 3.9 x 10(-)(6) M beta-C(12)G(2) in the presence of
      0.2 M NaCl. The theory of nucleation hole formation in NBFs was applied to
      describe the observed dependencies of the permeability and film stability on the
      surfactant concentration. The theory gave satisfactory relation to the
      experiment.

PMID- 16952232
TI  - Acid-base equilibria and dynamics in sodium dodecyl sulfate micelles: geminate
      recombination and effect of charge stabilization.
AB  - The synthetic flavylium salt 4-carboxy-7-hydroxy-4'-methoxyflavylium chloride
      (CHMF) exhibits two acid-base equilibria in the range of pH 1-8 in both aqueous
      and micellar sodium dodecyl sulfate (SDS) solutions. The values of pK(a1) and
      pK(a2) for the cation-zwitterion (AH(2)(+) <--> Z + H(+)) and the zwitterion-base
      (Z <--> A(-) + H(+)) equilibria increase from 0.73 and 4.84 in water to 2.77 and
      5.64 in SDS micelles, respectively. The kinetic study of the Z <--> A(-) + H(+)
      ground-state reactions in SDS points to the diffusion-controlled protonation of
      A(-) in the aqueous phase (k(p2w) = 4.2 x 10(10) M(-)(1) s(-)(1)) and in the
      micelle (k(p2m) = 2.3 x 10(11) M(-)(1) s(-)(1)). The deprotonation rate of Z did
      not significantly change upon going from water (k(d2) = 6.3 x 10(5) s(-)(1)) to
      SDS (k(d2) = 5.2 x 10(5) s(-)(1)), in contrast with the behavior of ordinary
      cationic flavylium salts, for which k(d2) strongly decreases in SDS micelles.
      These results suggest that deprotonation of the zwitterionic acid is not
      substantially perturbed by the micellar charge. Electronic excitation of the Z
      form of CHMF induces fast adiabatic deprotonation of the hydroxyl group of Z()
      (2.9 x 10(10) s(-)(1) in water and 8.4 x 10(9) s(-)(1) in 0.1 M SDS), followed by
      geminate recombination on the picosecond time scale. Interestingly, while
      recombination in water (k(rec) = 1.7 x 10(9) s(-)(1)) occurs preferentially at
      the carboxylate group, at the SDS micelle surface, recombination (k(rec) = 9.2 x
      10(9) s(-)(1)) occurs at the hydroxyl group. The important conclusion is that
      proton mobility at the SDS micelle surface is substantially reduced with respect
      to the mobility in water, which implies that geminate recombination should be a
      general phenomenon in SDS micelles.

PMID- 16952233
TI  - Autoxidized phospholipids in hexane: nano-self-assemblies studied by synchrotron
      small-angle X-ray scattering.
AB  - Synchrotron small-angle X-ray scattering (SAXS) was used to analyze the structure
      of self-assembled autoxidized phospholipids in a very dilute solution of hexane.
      In addition, it was used to build a self-consistent model of the aggregates,
      taking into account their inner heterogeneities and polydispersity. The
      scattering intensity from a dilute mixture of different types of noninteracting
      components of the phospholipid system was represented as a linear combination of
      partial intensities from the components weighted by their volume fractions.
      Applying this approach the final model of the system was described as a mixture
      of polydisperse reverse micelles and aggregates with spherical and cylindrical
      shapes. Spherical aggregates were represented as hollow spheres with inner radius
      0.7 nm (occupied by water or hexane) and outer radius 1.5 nm. Geometrical
      parameters of the aggregates did not change much during the oxidation process,
      while the ratio of reverse micelles and aggregates in solution varied. The amount
      of the reverse micelles increased from very low to about 80%, whereas the content
      of other aggregates constantly reduced. The analysis performed in this study
      helps one to better understand the processes of phospholipid oxidation, which may
      occur in biological membranes.

PMID- 16952234
TI  - Calorimetric investigation of the interaction between lithium perfluorononanoate
      and poly(ethylene glycol) oligomers in water.
AB  - The interaction of lithium perfluorononanoate (LiPFN) with poly(ethylene glycol)
      (PEG) molecules of different molecular weights (300 < MW < 20000 Da) has been
      investigated in water at 298.15 and 308.15 K by isothermal titration calorimetry
      (ITC). Density, viscosity, and conductivity measurements were also performed at
      298.15 K. The aggregation process of this surfactant on the PEG polymeric chain
      was found to be very similar to that exhibited by cesium perfluorooctanoate
      (CsPFO) and appears to be consistent with the necklace model. ITC titrations
      indicated that a fully formed LiPFN micellar cluster can be wrapped by a PEG
      chain having a molecular weight (MW) of approximately 3200 Da, longer than that
      required by the shorter perfluorooctanoate (MW approximately 2600 Da), and also
      suggested a stepwise mechanism for the aggregation of successive micelles.
      Viscosity data indicate that the formation of polymer-surfactant complexes
      between PEG and LiPFN involves a conformational change of the polymer. The
      aggregation of preformed micelles of LiPFN or CsPFO or SDS on the PEG polymeric
      chain always gives rise to further stabilization.

PMID- 16952235
TI  - Synthesis of nanometer-scale polymeric structures on surfaces from template
      assisted admicellar polymerization: a comparative study with protein adsorption.
AB  - A novel method for the formation of nanometer-scale polymer structures via
      template assisted admicellar polymerization (TAAP) is described. Admicellar
      polymerization uses a surfactant layer adsorbed on a surface to localize monomer
      to the surface prior to polymerization of the monomer. Nanostructures are formed
      by restricting adsorption to the uncovered sites of an already-templated surface,
      in this case to the interstitial sites between adsorbed latex spheres. Unlike
      most other process that form polymer nanostructures, polymer dimensions can be
      significantly smaller than the interstitial size because of sphere-surfactant
      interactions. Protein adsorption in the interstitial sites of colloidal arrays
      was also studied for three different proteins, and the results were compared with
      those obtained via admicellar polymerization.

PMID- 16952236
TI  - Phase behavior, topology, and growth of neutral catanionic reverse micelles.
AB  - The ternary catanionic system octylammoniumoctanoate/octane/water is studied by
      combined SANS, light scattering, conductivity, and phase diagram approach in the
      water-poor microemulsion region. The sphere-to-cylinder growth and branching
      depends on the concentration, the water-to-surfactant ratio, and the temperature.
      The unidimensional growth leads to a network of interconnected wormlike micelles.
      Like most studied linear nonionic surfactants, in this true catanionic system at
      equimolarity of anionic and cationic surfactant, the curvature toward water
      increases with temperature, making connections between cylinders less frequent.

PMID- 16952237
TI  - Formation of parallel strips in thin films of polystyrene/poly(vinyl pyrrolidone)
      blends via spin coating on unpatterned substrates.
AB  - Patterns of parallel strips, consisting of alternating polystyrene (PS) and
      poly(vinyl pyrrolidone) (PVP) regions, were observed in thin films spin cast from
      a PS/PVP/chloroform solution on unpatterned substrates. The formation of
      anisotropic patterns, manifested not only in thickness variation but also in
      composition variation, was found to be driven by Marangoni instability, with the
      PS and PVP streams flowing toward the preferred regions as the phase separation
      induced by solvent evaporation proceeded. The initial viscosity of the polymer
      solution and the thickness of the spin-cast films were lumped into one single
      parameter to study the phase morphology development at various initial polymer
      solution concentrations. Interestingly, the ratio of the square of the film
      thickness to the viscosity, a parameter loosely related to the Marangoni number,
      was found to reach a maximum value at the concentration where the strip patterns
      were most well-developed.

PMID- 16952238
TI  - Adsorption of organosilanes at a Zn-terminated ZnO (0001) surface: molecular
      dynamics study.
AB  - Four different organosilanes (octyltrihydroxysilane, butyltrihydroxysilane,
      aminopropyltrihydroxysilane, and thiolpropyltrihydroxysilane) adsorbed at a
      reconstructed Zn-terminated polar ZnO (0001) surface are studied via constant
      temperature (298 K) molecular dynamics simulations. Both single adsorbed silane
      molecules as well as adsorbed silane layers are modeled, and the energy,
      distance, orientation, and alignment of these adsorbates are analyzed. The
      adsorbed silane molecules exhibit behavior depending on the chemical nature of
      their tail (nonpolar or polar) as well as on the silane concentration at the
      solid surface (single adsorption or silane layer). In contrast to the O
      terminated ZnO surface studied previously, now adsorption can only occur at the
      vacancies of this reconstructed crystal surface, thus leading to an arched
      structure of the liquid phase near the crystal surface. Nevertheless, both
      nonpolar and polar single adsorbed silanes show a similar orientation and
      alignment at the surface (orthogonal in the former, parallel in the latter case)
      as for the O-terminated ZnO surface, although the interaction energy with the
      surface is considerably increased for nonpolar silanes while it is nearly
      unaffected for the polar ones. For adsorbed silanes within silane layers, the
      difference to single adsorbed silanes depends on the polarity of the tail:
      nonpolar silanes again show an orthogonal alignment, while polar silanes exhibit
      two different orientations at the solid surface-a head and a tail down
      configuration. This leads to two completely different but nevertheless stable
      orientations of these silanes at the Zn-terminated ZnO surface.

PMID- 16952239
TI  - Structure and organization of hexadecanol isomers adsorbed to the air/water
      interface.
AB  - The structure and 2D phase behavior of hexadecanol isomers adsorbed to the
      air/water interface have been studied using surface tension methods and
      vibrational sum frequency spectroscopy. Isomers include the linear 1-hexadecanol
      as well isomers with the alcohol functional group in the 2, 3, and 4 positions.
      Surface-pressure isotherms highlight how the 2D phase behavior of these
      monolayers depends sensitively on registry and packing efficiency between the
      alkyl chains whereas vibrational sum frequency spectroscopy, which is vibrational
      spectroscopy with surface specificity, reveals details about the molecular
      structure and orientation of molecules within the monolayer films at their
      equilibrium spreading pressures. At their equilibrium spreading pressures, both 1
      and 2-hexadecanol form compact films having a high degree of conformational
      order and molecular areas of 18.9 and 21.5 A(2)/molecule, respectively. This
      result for 2-hexadecanol implies that the isomer remains primarily in an all
      trans conformation with the methyl group in the C(1) position buried in the water
      subphase. This conformation leads to significantly reduced intensity in specific
      vibrational transitions due to partial destructive interference. In contrast, 3
      hexadecanol and 4-hexadecanol form more expanded monolayers at their equilibrium
      spreading pressures, having areas of 28.7 and 40.3 A(2)/molecule, respectively.
      In these monolayers, the intensities of selected vibrational bands show less
      evidence of destructive interference, implying that methyl groups on opposite
      ends of the adsorbates do not adopt strongly correlated orientations.

PMID- 16952240
TI  - Decarboxylation of 6-nitrobenzisoxazole-3-carboxylate in mixed micelles of
      zwitterionic and positively charged surfactants.
AB  - The rate of decarboxylation of 6-nitrobenzisoxazole-3-carboxylate, NBOC, was
      determined in micelles of N-hexadecyl-N,N,N-trimethylammonium bromide or chloride
      (CTAB or CTAC), N-hexadecyl-N,N-dimethyl-3-ammonium-1-propanesulfonate (HPS), N
      dodecyl-N,N-dimethyl-3-ammonium-1-propanesulfonate (DPS), N-dodecyl-N,N,N
      trimethylammonium bromide (DTAB), hexadecylphosphocholine (HPC), and their
      mixtures. Quantitative analysis of the effect on micelles on the velocity of NBOC
      decarboxylation allowed the estimation of the rate constants in the micellar
      pseudophase, k(m), for the pure surfactants and their mixtures. The extent of
      micellar catalysis for NBOC decarboxylation, expressed as the ratio k(m)/k(w),
      where k(w) is the rate constant in water, varied from 240 for HPS to 62 for HPC.
      With HPS or DPS, k(m) decreased linearly with CTAB(C) mole fraction, suggesting
      ideal mixing. With HPC, k(m) increased to a maximum at a CTAB(C) mole fraction of
      ca. 0.5 and then decreased at higher CTAB(C). Addition of CTAB(C) to HPC, where
      the negative charge of the surfactant is close to the hydrophobic core, produces
      tight ion pairs at the interface and, consequently, decreases interfacial water
      contents. Interfacial dehydration at the surface in equimolar HPC/CTAB(C)
      mixtures, and interfacial solubilization site of the substrate, can explain the
      observed catalytic synergy, since the rate of NBOC decarboxylation increases
      markedly with the decrease in hydrogen bonding to the carboxylate group.

PMID- 16952241
TI  - Aqueous nonionic copolymer-functionalized laponite clay. A thermodynamic and
      spectrophotometric study to characterize its behavior toward an organic material.
AB  - The affinity of functionalized Laponite clay toward an organic material in the
      aqueous phase was explored. Functionalization was performed by using triblock
      copolymers based on ethylene oxide (EO) and propylene oxide (PO) units that are
      EO(11)PO(16)EO(11) (L35) and PO(8)EO(23)PO(8) (10R5). Phenol (PhOH) was chosen as
      organic compound, which represents a contaminant prototype. To this purpose,
      densities and enthalpies of mixing as well as PhOH UV-absorption spectra were
      determined. The enthalpy and the spectrophotometry revealed PhOH-Laponite
      interactions whereas the volume did not. It emerged that the area occupied by
      PhOH on the Laponite surface is equal to that computed from the partial molar
      volume of PhOH in water, corroborating the insensitivity of the experimental
      volumes to the adsorption process. The situation where both PhOH and copolymer
      are simultaneously present in the aqueous Laponite suspension was also
      investigated. It turned out that the copolymer replaces PhOH from the
      water/Laponite clay interface, resulting in L35 being the more efficient.
      Moreover, the lateral copolymer-phenol interactions enhance the anchoring of PhOH
      to the solid surface. The reverse copolymer exercises the most important relevant
      effect. The UV-absorption spectra of PhOH in the water + copolymer + Laponite
      mixtures provided information that is consistent with those given by the
      calorimetric experiments. In conclusion, the aqueous copolymer-functionalized
      Laponite presents surface properties very different from the bare Laponite,
      favoring the removal of the organic compound from the solid surface.

PMID- 16952242
TI  - Consistent approach to adsorption thermodynamics on heterogeneous surfaces using
      different empirical energy distribution models.
AB  - Adsorption on heterogeneous surfaces with three basic energy distribution models
      (uniform model, exponential model, and normal-like model) is studied. Exact
      analytical solutions of the adsorption isotherms and the heats of adsorption are
      derived for the uniform and exponential models, and, with these solutions
      including a numerical solution for the normal-like model, the behavior of the
      differential heat of adsorption and the "apparent" standard adsorption entropy
      concerning the overall surface is described as a function of coverage and
      temperature. The approximations underlying the isotherms and heats of adsorption
      in the Temkin, Freundlich, and Langmuir-Freundlich types of adsorption are
      rationalized. By comparing these empirical formulas to the exact solutions, the
      level of these approximations is found to be identical, which is similar to the
      "condensation approximation". Their preconditions are that either the temperature
      is low enough, or the surface is strongly heterogeneous. Generally, they are
      suitable for the middle coverage range. The exact solutions provide a method to
      obtain more information on the heats, entropy, and heterogeneity of the catalyst
      surface from the calorimetric measurement of the heat of adsorption.

PMID- 16952243
TI  - Template-directed adsorption of block copolymers on alkanethiol-patterned gold
      surfaces.
AB  - Functionalized alkanethiols have been self-assembled on gold to modify the
      wetting properties of the surface and promote or hinder the adsorption of block
      copolymers containing both hydrophobic and hydrophilic blocks. X-ray
      photoelectron spectroscopy (XPS) studies of spin-coated polyethylene-block
      poly(ethylene oxide) (PE-b-PEO) copolymers on 16-mercaptohexadecanoic acid (MHDA)
      , octadecanethiol (ODT)-, and 1H,1H,2H,2H-perfluorodecanethiol (PFDT)-covered
      surfaces have been performed. In the case of an 80 wt % PEO block copolymer, spin
      coating on a gold surface precovered with MHDA results in a polymer film thick
      enough to completely attenuate Au 4f photoelectrons; spin-coating on the more
      hydrophobic ODT and PFDT monolayers leads to significantly thinner polymer films
      and incomplete attenuation of the gold photoelectrons. The opposite results are
      observed when a 20 wt % PEO block copolymer is used. Angle-resolved XPS studies
      of the 80 wt % PEO block copolymer spin-coated onto an MHDA-covered surface
      indicate that the PE blocks of the polymer segregate to the near-surface region,
      oriented away from the hydrophilic carboxylic acid tails of the monolayers; the
      surface concentration of PE is further enhanced by annealing at 90 degrees C.
      Microcontact printing and dip-pen nanolithography have been used to pattern gold
      surfaces with MHDA, and the surfaces have been backfilled with ODT or PFDT, such
      that the unpatterned regions of the surface are covered with hydrophobic
      monolayers. In the case of backfilling with PFDT, spin-coating the 80 wt % PEO
      copolymer onto these patterned surfaces and subsequent annealing results in the
      block copolymer preferentially adsorbing on the MHDA-covered regions and forming
      well-defined patterns that mimic the MHDA pattern, as determined by scanning
      electron microscopy and atomic force microscopy. Significantly worse patterning,
      characterized by micron-sized polymer droplets, results when the surface is
      backfilled with ODT instead of PFDT. Using PFDT and MHDA, polymer features having
      widths as small as 500 nm have been formed. These studies demonstrate a novel
      method to pattern block copolymers with nanoscale resolution.

PMID- 16952244
TI  - Template-assisted patterning of nanoscale self-assembled monolayer arrays on
      surfaces.
AB  - We report a general, simple, and inexpensive approach to pattern features of self
      assembled monolayers (SAMs) on silicon and gold surfaces using porous anodic
      alumina films as templates. The SAM patterns, with feature sizes down to 30 nm
      and densities higher than 10(10)/cm(2), can be prepared over large areas (>5
      cm(2)). The feature dimensions can be tuned by controlling the alumina template
      structure. These SAM patterns have been successfully used as resists for
      fabricating gold and silicon nanoparticle arrays on substrates by wet-chemical
      etching. In addition, we show that arrays of gold features can be patterned with
      10-nm gaps between the dots.

PMID- 16952245
TI  - Facile method to prepare surface-enhanced-Raman-scattering-active Ag
      nanostructures on silica spheres.
AB  - In this paper we describe a very simple electroless plating method used to
      prepare Ag-coated silica beads. Robust Ag nanostructures can be reproducibly
      fabricated by soaking silica beads in ethanolic solutions of AgNO(3) and
      butylamine. When the molar ratio of butylamine to AgNO(3) is far below 1.0,
      distinct nanosized Ag particles are formed on the silica beads, but by increasing
      the amount of butylamine, network-like Ag nanostructures are formed that possess
      very broad UV/vis absorption characteristics extending from near-UV to near
      infrared regions. In conformity with the UV/vis absorption characteristics, the
      Ag-deposited silica beads were highly efficient surface-enhanced Raman scattering
      (SERS) substrates, with the enhancement factor estimated using benzenethiol as a
      model adsorbate to be larger than 10(6). Since another silica layer can be
      readily deposited onto the Ag surface, the Ag-coated silica beads should be
      invaluable in the development of SERS-based biosensors.

PMID- 16952246
TI  - Defect evolution in block copolymer thin films via temporal phase transitions.
AB  - We study the details of the defect dynamics in thin films of a cylinder-forming
      polystyrene-block-polybutadiene (SB) diblock copolymer melt. The high temporal
      resolution of in-situ scanning force microscopy (SFM) uncovers elementary dynamic
      processes of structural rearrangements on time scales not accessible so far.
      Short-term interfacial undulations and the formation of transient phases
      (spheres, perforated lamellae, and lamellae) are observed. We demonstrate that
      the well-known structural defects are annihilated by short-term phase transitions
      into what may be considered excited states. These temporary phase transitions are
      reproduced in simulations based on dynamic self-consistent field theory. We
      discuss the role of the observed structural evolution in the context of the
      equilibrium phase behavior in SB thin films.

PMID- 16952247
TI  - Structures of dense glycine and alanine adlayers on chiral Cu(3,1,17) surfaces.
AB  - Density Functional Theory calculations have been used to predict the structures
      of dense glycine and alanine adlayers on Cu(3,1,17)(S). Facets of this chiral Cu
      surface result from adsorbate-induced surface reconstruction when glycine or
      alanine are adsorbed and annealed on Cu(100). We have calculated the surface
      energy changes associated with this surface reconstruction. Our results allow the
      enantiospecificity of this reconstruction following adsorption of enantiopure or
      racemic alanine on Cu(100) to be discussed. The overall stability of glycine and
      alanine adlayers on Cu(3,1,17)(S) arises from an interplay between the formation
      of chemical bonds with the Cu surface, deformations in the adsorbed molecules
      during adsorption, and intermolecular hydrogen bonds within the adlayer; none of
      these factors individually dominates.

PMID- 16952248
TI  - Cluster properties of peptides on (100) semiconductor surfaces.
AB  - Peptide adhesion on semiconductor surfaces is quantitatively investigated by
      atomic force microscopy. The selected peptides are shown to cluster at the
      surface, with the larger, higher, and softer clusters appearing on the surfaces
      with lower peptide adhesion. Average cluster diameters vary from 40 nm on GaAs
      (100) to 300 nm on Si (100). Direct adhesion of the peptides to the surface
      competes with forming molecular aggregates that offer an overall reduced surface
      contact.

PMID- 16952249
TI  - Electrochemically controlled formation and growth of hydrogen nanobubbles.
AB  - Electrogenerated microscale bubbles that are confined at the electrode surface
      have already been extensively studied because of their significant influence on
      electrochemistry. In contrast, as far as we know, whether nanoscale bubbles exist
      on the electrode surface has not been experimentally confirmed yet. Here, we
      report the observation of electrochemically controlled formation and growth of
      hydrogen nanobubbles on bare highly oriented pyrolytic graphite (HOPG) surface
      via in-situ tapping mode atomic force microscopy (TMAFM). By using TMAFM imaging,
      we observed that electrochemically generated hydrogen gas led to the formation of
      nanobubbles at the HOPG surface. We then employed a combination of techniques,
      including phase imaging, ex-situ degassing, and tip perturbation, to confirm the
      gas origin of such observed nanobubbles. We further demonstrated that the
      formation and growth of nanobubbles could be well controlled by tuning either the
      applied voltage or the reaction time. Remarkably, we could also monitor the
      evolution process of nanobubbles, that is, formation, growth, coalescence, as
      well as the eventual release of merged microbubbles from the HOPG surface.

PMID- 16952250
TI  - Entrapment of photosystem I within self-assembled films.
AB  - We have developed a process to incorporate an integral membrane protein,
      Photosystem I (PSI), into an organic thin film at an electrode surface and
      thereby insulate the protein complex on the surface while mimicking its natural
      environment. The PSI complex, which is primarily more hydrophobic on the exterior
      than interior, is hydrophobically confined in vivo within the thylakoid membrane.
      To mimic the thylakoid membrane and entrap PSI on an electrode, we have designed
      a series of steps using a thin self-assembled monolayer (SAM) to adsorb and
      orient PSI followed by exposures to longer-chained methyl-terminated alkanethiols
      that place exchange with components of the original SAM in the interprotein
      domains. In this process, PSI is first adsorbed onto a HOC(6)S/Au substrate
      through a short exposure to a dilute solution of the protein to achieve a protein
      coverage of approximately 25%. The PSI/HOC(6)S/Au substrate is then placed into a
      solution containing one of various longer-chained alkanethiols including C(22)SH
      or C(18)OC(19)SH. Changes in thickness, interfacial capacitance, infrared
      spectra, and surface wettability were used to assess the extent of backfilling by
      the long-chained thiols. The coverage of the protein layer and the solvent used
      for backfilling affected the rate and quality of the SAM formed in the
      interprotein regions. After exposure of the PSI layer to solvents containing
      alkanethiols, there was only minor loss of protein on the surface and no real
      change in protein secondary structure as evidenced by reflectance absorption
      infrared spectroscopy.

PMID- 16952251
TI  - Photochemical functionalization of gallium nitride thin films with molecular and
      biomolecular layers.
AB  - We demonstrate that photochemical functionalization can be used to functionalize
      and photopattern the surface of gallium nitride crystalline thin films with well
      defined molecular and biomolecular layers. GaN(0001) surfaces exposed to a
      hydrogen plasma will react with organic molecules bearing an alkene (C=C) group
      when illuminated with 254 nm light. Using a bifunctional molecule with an alkene
      group at one end and a protected amine group at the other, this process can be
      used to link the alkene group to the surface, leaving the protected amine
      exposed. Using a simple contact mask, we demonstrate the ability to directly
      pattern the spatial distribution of these protected amine groups on the surface
      with a lateral resolution of <12 mum. After deprotection of the amines, single
      stranded DNA oligonucleotides were linked to the surface using a bifunctional
      cross-linker. Measurements using fluorescently labeled complementary and
      noncomplementary sequences show that the DNA-modified GaN surfaces exhibit
      excellent selectivity, while repeated cycles of hybridization and denaturation in
      urea show good stability. These results demonstrate that photochemical
      functionalization can be used as an attractive starting point for interfacing
      molecular and biomolecular systems with GaN and other compound semiconductors.

PMID- 16952252
TI  - Core-corona polymer composite particles by self-assembled heterocoagulation based
      on a hydrogen-bonding interaction.
AB  - Poly(ethylene glycol dimethacrylate-co-acrylic acid) (poly(EGDMA-co-AA)) small
      microspheres were effectively self-assembled on poly(ethylene glycol
      dimethacrylate-co-4-vinylpyridine) (poly(EGDMA-co-VPy)) surfaces to form a core
      corona structure with a raspberry-like polymer composite by a hydrogen
      interaction mechanism through an affinity complex between the carboxylic acid
      group and pyridine group. The control of coverage of the poly(EGDMA-co-AA) corona
      on the surface of poly(EGDMA-co-VPy) was studied in detail via adjustment of the
      nature of the mass ratio between the core and corona. The effects of the pH and
      solvent used on the morphology of the self-assembled core-corona polymer
      composites were investigated. The nature of the interaction between the core and
      corona polymer particles was identified as hydrogen bonding with FT-IR
      spectroscopy.

PMID- 16952253
TI  - Redox-active biomolecular architectures and self-assembled monolayers based on a
      cyclodecapeptide regioselectively addressable functional template.
AB  - A nanometer scale redox active biomolecular architecture has been successfully
      synthesized through an efficient chemoselective oxime based coupling between
      ferrocenyl groups and a regioselectively addressable cyclodecapeptide. This
      molecular tool exhibits electronic, structural, and chemical properties driven by
      the biomimetic recognition activity of the polypeptide skeleton associated to the
      well-defined electrochemical activity of metallocenyl probes. Biomolecular
      materials obtained by confinement of the redox cyclopeptide in self-assembled
      monolayers on gold surfaces shows efficient through-bond electron transfer from
      the ferrocenes to the electrode surface via the peptidic backbone, as well as
      markedly improved sensing properties toward anionic species in organic
      electrolyte, as compared to those observed in homogeneous solution.

PMID- 16952254
TI  - Novel tertiary amine oxide surfaces that resist nonspecific protein adsorption.
AB  - Novel surfaces derivatized with tertiary amine oxides have been prepared and
      tested for their ability to resist nonspecific protein adsorption. The oxidation
      of tertiary amines supported on triazine units was carried out using mCPBA to
      give a format allowing conjugation of biologically active ligands alongside them.
      Adsorption to these surfaces was tested and compared to adsorption to a set of
      commercial and custom oligo-/poly(ethylene glycol) (OEG/PEG) supports by
      challenging them with a protein display library presented on bacteriophage
      lambda. The new class of amine oxide surfaces is found to compare favorably with
      the performance of the OEG/PEG supports in the prevention of nonspecific binding.

PMID- 16952256
TI  - Cisplatin nanoliposomes for cancer therapy: AFM and fluorescence imaging of
      cisplatin encapsulation, stability, cellular uptake, and toxicity.
AB  - Cisplatin is the most effective cytotoxic agent against many cancers. Its usage,
      however, is limited due to inefficient uptake by the target cells. A liposomal
      formulation of cisplatin is reported to partly overcome this limitation.
      Physicochemical characteristics of the liposome-cisplatin preparation, including
      its size, stability, encapsulation efficiency, and cytoplasmic internalization
      efficiency, play a significant role in an effective usage of liposomal
      formulations. We have used atomic force microscopy (AFM) to determine
      physicochemical characteristics of cisplatin-encapsulated liposomes, AFM and
      fluorescence microscopy to examine their cytoplasmic internalization, and
      Live/Dead assay to examine their cell toxicity. Nonencapsulated cisplatin is
      globular and 10-50 nm in size. AFM force-dissection and stiffness measurements
      show that cisplatin-encapsulated liposomes are significantly stiffer (
      approximately 100%) and more stable than liposomes without encapsulated
      cisplatin. Cisplatin-encapsulated liposomes of approximately 250 nm diameter
      (nanoliposomes) are most efficiently internalized and induce cell toxicity in a
      time-dependent manner. Liposomes without cisplatin of similar dimensions,
      although internalized in the cell cytoplasm, do not induce cell toxicity.

PMID- 16952255
TI  - Cell mechanics using atomic force microscopy-based single-cell compression.
AB  - We report herein the establishment of a single-cell compression method based on
      force measurements in atomic force microscopy (AFM). The high-resolution bright
      field or confocal laser scanning microscopy guides the location of the AFM probe
      and then monitors the deformation of cell shape, while microsphere-modified AFM
      probes compress the cell and measure the force. Force and deformation profiles of
      living cells reveal a cubic relationship at small deformation (<30%), multiple
      peaks at 30-70% compression, and a rapid increase at over 80% deformation. The
      initial compression may be described qualitatively and quantitatively using a
      simple model of a nonpermeable balloon filled with incompressible fluid. Stress
      peaks reflect cell membrane rupture, followed by the deformation and rupture of
      intracellular components, beyond which the cell responses become irreversible.
      The Young's modulus and bending constant of living cell membranes are extracted
      from the balloon models, with 10-30 MPa and 17-52 kT, respectively. The initial
      compression of dead and fixed cells is modeled using Hertzian contact theory,
      assuming that the cell is a homogeneous sphere. Dead cells exhibit a cytoskeleton
      elasticity of 4-7.5 kPa, while fixation treatment leads to a dramatic increase in
      the cytoskeletal Young's modulus (150-230 kPa) due to protein cross-linking by
      imine bonds. These results demonstrate the high sensitivity of the single-cell
      compression method to the molecular-level structural changes of cells, which
      suggests a new generic platform for investigating cell mechanics in tissue
      engineering and cancer research.

PMID- 16952257
TI  - Using bicellar mixtures to form supported and suspended lipid bilayers on silicon
      chips.
AB  - Bicellar mixtures, planar lipid bilayer assemblies comprising long- and short
      chain phosphatidylcholine lipids in suspension, were used to form supported lipid
      bilayers on flat silicon substrate and on nanotextured silicon substrates
      containing arrays of parallel troughs (170 nm wide, 380 nm deep, and 300 nm
      apart). Confocal fluorescence and atomic force microscopies were used to
      characterize the resulting lipid bilayer. Formation of a continuous biphasic
      undulating lipid bilayer membrane, where the crests and troughs corresponded to
      supported and suspended lipid bilayer regions, is demonstrated. The use of
      interferometric lithography to fabricate nanotexured substrates provides an
      advantage over other nanotextured substrates such as nanoporous alumina by
      offering flexibility in designing different geometries for suspending lipid
      bilayers.

PMID- 16952258
TI  - Lipase-catalyzed reactions at different surfaces.
AB  - Starting from gold chips, we have tailor-made three surfaces by the self-assembly
      monolayer technique: one entirely hydrophobic, one hydrophobic with dispersed
      carboxyl groups, and one hydrophilic, containing hydroxyl groups. Rhizomucor
      miehei lipase has been adsorbed to the hydrophobic and the hydrophilic surfaces
      and covalently bound to the surface containing carboxyl groups. The adsorption of
      two substrates-capric acid (decanoic acid) and monocaprin-on the lipase-covered
      surfaces was monitored by the surface plasmon resonance (SPR) technique.
      Biocatalysis was also performed in the SPR instrument by circulating a solution
      of the substrate, dissolved in an 85:15 water-glycerol mixture at a(w) = 0.81,
      through the instrument, thus exposing the capric acid or the monocaprin to the
      lipase-covered surfaces. The product composition was found to depend on the type
      of surface used. Lipase adsorbed at the hydrophilic surface favored hydrolysis,
      and capric acid was the main product formed when monocaprin was used as
      substrate. Lipase adsorbed at a hydrophobic surface and, in particular, lipase
      covalently bound to a hydrophobic surface favored condensation. More dicaprin
      than capric acid was formed in experiments with monocaprin as the substrate.
      Reactions performed outside the SPR instrument showed that small amounts of
      triglyceride were also formed under these conditions. We believe that this work
      constitutes the first example of the SPR instrument being used for in-situ
      biotransformation.

PMID- 16952259
TI  - Macrophage uptake of core-shell nanoparticles surface modified with poly(ethylene
      glycol).
AB  - The in vitro uptake of core-shell nanoparticles encapsulated in a bio
      macromolecular nanoshell assembled from multilayered polyelectrolytes was
      studied. Sulfate modified fluorescent polystyrene nanobeads (diameter 200 nm)
      were used as a solid core upon which charged multilayers of poly-l-lysine,
      chitosan, and heparin sulfate are electrostatically deposited utilizing a layer
      by-layer (LbL) self-assembly process. The nanoshell composed of the multilayered
      polyelectrolytes was modified with poly(ethylene glycol) (PEG) of varying
      molecular weights (either MW 2000, 5000, or 20 000 Da) to form a hydrophilic and
      long-circulating nanoparticle. The assembly of the nanoshell was confirmed by
      zeta potential, transmission electron microscopy (TEM), and X-ray photoelectron
      spectroscopy (XPS). The reversal in charge upon the deposition of alternating
      polyelectrolytes was observed by zeta potential measurements. The nanometer
      thickness of the nanoshell was confirmed by TEM. The presence of the (C-C-O)(n)()
      backbone in PEG at the surface of the nanoshell was confirmed by the increase in
      (C-O,N) peak area concentrations compared to (C-C) peak area, and these results
      were gathered from XPS. In vitro studies between suspension macrophages and core
      shell nanoparticles were performed to determine how the hydrophilicity and the
      charge on the nanoshell can promote or reduce uptake. Results showed that after
      24 h uptake was decreased 3-fold when PEGs of 2000 and 20 000 Da were chemisorbed
      to the nanoshell, as opposed to a nanoshell with either a positive or highly
      negative charge. Confocal microscopy aided in verifying that core-shell
      nanoparticles were internalized within the cell cytoplasm and were not attached
      to the cell surface. Protein adhesion studies with bovine serum albumin were
      performed to determine the relationship between surface charge and opsonization
      of core-shell nanoparticles. It was found that a hydrophilic surface with a low
      negative charge reduced protein adsorption and uptake. The in vitro uptake of
      macrophages and protein adsorption onto core-shell nanoparticles formed using
      layer-by-layer assembly has not been previously studied.

PMID- 16952260
TI  - Strong resistance of a thin crystalline layer of balanced charged groups to
      protein adsorption.
AB  - Resistance of mixed self-assembled monolayers (SAMs) with various counter-charged
      terminal groups of different valence and protonation/deprotonation states to
      nonspecific protein adsorption is investigated. It is demonstrated that excellent
      nonfouling surfaces can be readily constructed from mixed positively and
      negatively charged components of equal valence in a wide range of thiol solution
      compositions. Furthermore, the lattice structure of one of the mixed SAM systems
      studied is revealed by atomic force microscopy (AFM) to be (5.2 +/- 0.2 A x 5.2
      +/- 0.2 A)60 degrees . Results indicate that the packing structure of mixed
      charged SAMs is determined by strong charge-charge interactions of the terminal
      groups rather than S-Au and chain-chain interactions. This work provides direct
      evidence that conformational flexibility is not required for protein resistance
      of a surface and even a single compact layer of charged groups of balanced charge
      with a crystalline structure can resist nonspecific protein adsorption,
      suggesting that tightly bound water molecules on the topmost part of the mixed
      SAMs play a dominant role in surface resistance to nonspecific protein
      adsorption.

PMID- 16952261
TI  - Nonfouling characteristics of dextran-containing surfaces.
AB  - Hydroxyl groups in dextrans have been selectively oxidized to aldehyde groups by
      sodium periodate in a controlled fashion with a percentage of conversion ranging
      from 6 to 100%. Dextrans (10, 70, 148, 500, and 2000 kDa) and oxidized 10k
      dextrans have been successfully grafted to functionalized silicon surfaces. The
      effect of molecular weight on protein adsorption is not nearly as striking as
      that of the extent of oxidation. When approximately 25% of the hydroxyl groups
      have been converted to aldehyde groups, there is negligible protein adsorption on
      surfaces containing the oxidized polysaccharides. Conformations of grafted
      polymers depend strongly on their chemical structures, that is, the relative
      amounts of -OH and -CHO groups. The dependence of the chain conformation as well
      as the protein resistance on the balance of the hydrogen bond donors (-OH) and
      the acceptors (-OH and -CHO) implies the importance of chemical structure of
      surface molecules, specifically the interactions between surface and surrounding
      water molecules on protein adsorption. Oxidized dextrans are potential
      poly(ethylene glycol) alternatives for nonfouling applications.

PMID- 16952263
TI  - Synthesis of PNIPAM-co-MBAA copolymer nanotubes with composite control.
AB  - We report the preparation of copolymer, poly(N-isopropylacrylamide)-co-(N,N'
      methylenebisacrylamide) (PNIPAM-co-MBAA) nanotubes with different composite
      ratios through surface-initiated atom transfer radical polymerization using a
      porous anodic aluminum oxide membrane as a template. It is found that the tubular
      wall strongly depends on the monomer concentration. The composite-induced changes
      in dimension and shape of nanotubes, especially the wall thickness, were studied
      by scanning electron microscopy, transmission electron microscopy, atom force
      microscopy, FT-IR, and gel permeation chromatography. The PNIPAM-co-MBAA
      nanotubes exhibit a high flexibility and stability.

PMID- 16952262
TI  - Phosphonic acid monolayers for binding of bioactive molecules to titanium
      surfaces.
AB  - Two different phosphonic acid monolayer films for immobilization of bioactive
      molecules such as the protein BMP-2 on titanium surfaces have been prepared.
      Monolayers of (11-hydroxyundecyl)phosphonic acid and (12
      carboxydodecyl)phosphonic acid molecules were produced by a simple dipping
      process (the T-BAG method). The terminal functional groups on these monolayers
      were activated (carbonyldiimidazole for hydroxyl groups and N-hydroxysuccinimide
      for carboxyl groups) to bind amine-containing molecules. The reactivity of the
      surfaces was investigated using trifluoroethylamine hydrochloride and BMP-2. Each
      step of the surface modification procedure was characterized by X-ray
      photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry.

PMID- 16952264
TI  - Topography and surface energy dependent calcium phosphate formation on Sol-Gel
      derived TiO2 coatings.
AB  - Heterogeneous nucleation and growth of calcium phosphate (CaP) on sol-gel derived
      TiO(2) coatings was investigated in terms of surface topography and surface
      energy. The topography of the coatings was derived from AFM measurements, while
      the surface energy was determined with contact angle measurements. The degree of
      precipitation was examined with scanning electron microscopy (SEM) and X-ray
      photoelectron spectroscopy (XPS). The precipitation of CaP was found to be
      dependent on both topography and surface energy. A high roughness value when
      combining the RMS roughness parameter S(q) with the number of local maxima per
      unit area parameter S(ds) enhances CaP formation. The hydrophilicity of the
      coating was also found to be of importance for CaP formation. We suggest that the
      water contact angle, which is a direct measure of the hydrophilicity of the
      surface, may be used to evaluate the surface energy dependent precipitation
      kinetics rather than using the often applied Lewis base parameter.

PMID- 16952265
TI  - Surface-mediated synthesis and spectroscopic characterization of tantalum
      clusters on silica.
AB  - Tantalum clusters were synthesized on the surface of porous silica by treatment
      of adsorbed Ta(CH(2)Ph)(5) in H(2) at temperatures in the range of 523-723 K. The
      surface species were characterized by UV-vis, far-infrared, and extended X-ray
      absorption fine-structure (EXAFS) spectroscopies, each of which provided evidence
      of Ta-Ta bonds similar to those in well-characterized molecular tantalum
      clusters. The Ta-Ta distance determined by EXAFS spectroscopy was 2.93 A. The
      chemistry of the cluster synthesis is similar to that of syntheses of similar
      tantalum clusters in solution. The supported clusters formed at 523 K are
      characterized by an EXAFS first-shell Ta-Ta coordination number of nearly 2,
      indicative of tri-tantalum clusters, although it is expected that a mixture of
      clusters was present, and reduction in H(2) at higher temperatures led to larger
      tantalum clusters. This is the first example of the surface-mediated synthesis of
      an early transition metal cluster, and the supported clusters reported here are
      the first to have been characterized by all three of the spectroscopic methods
      mentioned above. The similarity of the surface synthesis to that in solution
      points to opportunities to extend this new class of material to other early
      transition metal clusters on various supports.

PMID- 16952266
TI  - Influence of kappa-carrageenan gel structures on the diffusion of probe molecules
      determined by transmission electron microscopy and NMR diffusometry.
AB  - The influence of the microstructures of different kappa-carrageenan gels on the
      self-diffusion behavior of poly(ethylene glycol) (PEG) has been determined by
      nuclear magnetic resonance (NMR) diffusometry and transmission electron
      microscopy (TEM). It was found that the diffusion behavior was determined mainly
      by the void size, which in turn was defined by the state of aggregation of the
      kappa-carrageenan. The kappa-carrageenan concentration was held constant at 1
      w/w%, and the aggregation was controlled by the amount of potassium and/or sodium
      chloride and, for samples containing potassium, also by the cooling rate. Gels
      containing potassium formed microstructures where kappa-carrageenan strands are
      rather evenly distributed over the image size, while sodium gels formed dense
      biopolymer clusters interspersed with large openings. In a gel with small void
      sizes, relatively slow diffusion was found for all PEG sizes investigated.
      Extended studies of the self-diffusion behavior of the 634 g mol(-)(1) PEG showed
      that there is a strong time dependence in the measured PEG diffusion. An
      asymptotic lower time limit of the diffusion coefficient was found in all gels
      when the diffusion observation time was increased. According to the ratio,
      D/D(0), where D(0) is the diffusion coefficient in D(2)O and D is the diffusion
      coefficient in the gels, the gels could be divided into three classes: small,
      medium, and large voids. For quenched kappa-carrageenan solutions with salt
      concentrations of 20 mM K(+), 100 mM K(+), or 20 mM K(+)/200 mM Na(+) as well as
      slowly cooled solutions with only 20 mM K(+), D/D(0) ratios between 0.18 and 0.29
      were obtained. By quenching a kappa-carrageenan solution with 100 mM K(+), the
      D/D(0) was 0.5, while D/D(0) ratios between 0.9 and 1 were obtained in a quenched
      solution with 250 mM Na(+) and slowly cooled samples with 20 mM K(+)/200 mM Na(+)
      or 250 mM Na(+).

PMID- 16952267
TI  - Characterization and methanol electrooxidation studies of Pt(111)/Os surfaces
      prepared by spontaneous deposition.
AB  - Catalytic activity of the Pt(111)/Os surface toward methanol electrooxidation was
      optimized by exploring a wide range of Os coverage. Various methods of surface
      analyses were used, including electroanalytical, STM, and XPS methods. The
      Pt(111) surface was decorated with nanosized Os islands by spontaneous
      deposition, and the Os coverage was controlled by changing the exposure time to
      the Os-containing electrolyte. The structure of Os deposits on Pt(111) was
      characterized and quantified by in situ STM and stripping voltammetry. We found
      that the optimal Os surface coverage of Pt(111) for methanol electrooxidation was
      0.7 +/- 0.1 ML, close to 1.0 +/- 0.1 Os packing density. Apparently, the high
      osmium coverage Pt(111)/Os surface provides more of the necessary oxygen
      containing species (e.g., Os-OH) for effective methanol electrooxidation than the
      Pt(111)/Os surfaces with lower Os coverage (vs e.g., Ru-OH). Supporting evidence
      for this conjecture comes from the CO electrooxidation data, which show that the
      onset potential for CO stripping is lowered from 0.53 to 0.45 V when the Os
      coverage is increased from 0.2 to 0.7 ML. However, the activity of Pt(111)/Os for
      methanol electrooxidation decreases when the Os coverage is higher than 0.7 +/-
      0.1 ML, indicating that Pt sites uncovered by Os are necessary for sustaining
      significant methanol oxidation rates. Furthermore, osmium is inactive for
      methanol electrooxidation when the platinum substrate is absent: Os deposits on
      Au(111), a bulk Os ingot, and thick films of electrodeposited Os on Pt(111), all
      compare poorly to Pt(111)/Os. We conclude that a bifunctional mechanism applies
      to the methanol electrooxidation similarly to Pt(111)/Ru, although with fewer
      available Pt sites. Finally, the potential window for methanol electrooxidation
      on Pt(111)/Os was observed to shift positively versus Pt(111)/Ru. Because of the
      difference in the Os and Ru oxophilicity under electrochemical conditions, the Os
      deposit provides fewer oxygen-containing species, at least below 0.5 V vs RHE.
      Both higher coverage of Os than Ru and the higher potentials are required to
      provide a sufficient number of active oxygen-containing species for the effective
      removal of the site-blocking CO from the catalyst surface when the methanol
      electrooxidation process occurs.

PMID- 16952268
TI  - Ion-exchange voltammetry with nafion/poly(sodium 4-styrenesulfonate) mixed
      coatings on mercury film electrodes: characterization studies and application to
      the determination of trace metals.
AB  - This work aimed to produce improved polymer coatings for the modification of thin
      mercury film electrodes (TMFEs). The goal is to obtain sensitive, reproducible,
      mechanically stable and antifouling devices suitable for the determination of
      trace metal cations in complex media. Therefore, novel mixed coatings of two
      sulfonated cation-exchange polymers of dissimilar characteristics-Nafion (NA) and
      poly(sodium 4-styrenesulfonate) (PSS)-were produced by solvent evaporation onto
      glassy carbon electrodes. The effect of the mass ratio (NA:PSS) on the film
      morphology was studied by scanning electron microscopy, revealing the formation
      of biphasic polymer systems, where PSS bead-shaped clusters appeared randomly
      dispersed into a uniform and compact NA environment. The permselectivity/ion
      exchange features of the mixed films onto glassy carbon were evaluated using
      cathecol, urate, and dopamine. To allow trace metal analysis, thin mercury films
      were plated through the NA/PSS coatings, being the reproducibility and ion
      exchange features of the mixed coatings-TMFE evaluated using lead ions. The best
      NA/PSS coating was found for the mass ratio of 5.3. Analytical performance of the
      NA/PSS-TMFE yielded a detection limit of 5.5 nM (3sigma), and the application of
      this modified electrode to an untreated polluted estuarine water sample produced
      significant improvements in the quality of the signal compared with that for a
      bare TMFE.

PMID- 16952269
TI  - Size selective assembly of colloidal particles on a template by directed self
      assembly technique.
AB  - We report a simple and effective approach to organize micron- and submicron-sized
      particles in a size selective manner. This approach utilizes the template
      assisted directed self-assembly technique. A topographically patterned
      photoresist surface is fabricated and used to create an ordered array of
      colloidal particles from their aqueous suspensions. Assembly of particles on this
      template is then achieved by using a conventional spin coating technique.
      Feasibility of this technique to form a large area of patterned particle
      assemblies has been investigated. To arrange the particles on the template, the
      physical confinement offered by the surface topography must overcome a joint
      effect of centrifugal force and the hydrophobic nature of the photoresist
      surface. This concept has been extended to the size selective sorting of
      colloidal particles. The capability of this technique for sorting and organizing
      colloidal particles of a particular diameter from a mixture of microspheres is
      demonstrated.

PMID- 16952270
TI  - Effect of additives on LiMo3Se3 nanowire film chemical sensors.
AB  - Here we investigate the effect of lithium iodide and cetyltrimethylammonium (CTA)
      bromide additives on the ability of LiMo(3)Se(3) nanowire film sensors to bind
      and detect organic solvents electrically. Both additives decrease the electrical
      conductivity of the films. Lithium iodide increases the response of the films to
      both polar and nonpolar analytes. CTA increases the response of the films to
      nonpolar analytes but reduces the response to polar analytes. Quartz crystal
      microbalance measurements show that the modified electrical sensitivities of the
      films are due to altered analyte adsorption abilities of the films. These results
      show that the Li(+) ions are involved in analyte binding in native LiMo(3)Se(3)
      films and that a programming of LiMo(3)Se(3) nanowire film sensors is possible by
      replacing lithium cations with other receptors.

PMID- 16952271
TI  - Micropatterning of living cells on a heterogeneously wetted surface.
AB  - We report a simple approach to fabricate heterogeneously wetted surfaces which
      can be used to pattern living cells or biomolecules. An array of pedestals
      composed of SU-8 was fabricated on a glass surface which was then derivatized
      with a hydrophobic silane. Upon addition of aqueous solutions to the array, air
      was trapped within the hydrophobic cavities between the pedestals. The trapped
      air formed a "virtual wall" blocking access to these cavities. Cells cultured on
      the array were forced to grow only on the tops of the pedestals, i.e., the
      surfaces wetted by aqueous media. The virtual walls were stable during
      manipulation of the array and over long time periods (months).

PMID- 16952272
TI  - Progressing the agenda for rural mental health research.

PMID- 16952273
TI  - Role of immunostimulatory DNA and TLR9 in gene therapy.
AB  - One of the key issues of DNA-based therapies is the immunostimulatory effect
      caused by DNA, which it has a significant impact on the consequences of these
      therapies. This is a result of the recognition by Toll-like receptor-9 (TLR9); a
      pattern recognition receptor for unmethylated CpG motifs within DNA sequences.
      However, recent studies show that TLR9 can recognize non-CpG motifs and induce
      cellular activation when DNA is efficiently delivered to TLR9, for example, by
      cationic lipids. Moreover, recent research shows that TLR9-independent
      immunoactivation could take place. Here, we have attempted to present an overview
      of immunoactivation by DNA to optimize DNA-based therapies.

PMID- 16952274
TI  - Approaches to oral drug delivery for challenging molecules.
AB  - Advances in biotechnology, high throughput screening and computational chemistry
      have led to a considerable increase in the number of protein and peptide
      therapeutics and other macromolecular drugs. Working with macromolecules,
      however, poses a number of challenges that must be overcome to successfully
      develop these compounds into safe and effective therapeutics. Significant efforts
      in pharmaceutical and academic laboratories have been expended in finding ways to
      deliver macromolecular drug molecules by the oral route, which can significantly
      improve patient compliance, convenience, and efficacy. Nevertheless, for a drug
      molecule to be orally bioavailable, it has to overcome the natural physiological
      processes of breaking down molecules in the gastrointestinal tract, and to
      traverse a relatively impermeable epithelial layer of cells that line the
      gastrointestinal tract. This article provides a summary of the challenges that
      researchers need to surmount in the development of orally absorbable peptide and
      protein drugs, and gives an overview of the novel approaches currently in
      progress in the field of oral delivery.

PMID- 16952275
TI  - RNA-interference effectors and their delivery.
AB  - RNA-interference, the mechanism by which the expression of a specific protein can
      be reduced or eliminated, has emerged as a potential way to treat disease. RNA
      interference effectors, such as small interfering RNA and small hairpin RNA, are
      double-stranded nucleic acid sequences expressly designed to have homology to
      sections of the target protein's mRNA, and when present in the cytosol trigger
      hydrolysis of the mRNA through the RNA-interference pathway. Because RNA
      interference effectors are macromolecular and typically polyanionic, their
      efficacy is poor when not accompanied by a delivery vehicle. This review outlines
      the RNA-interference mechanism and discusses the delivery of RNA-interference
      effectors, with an emphasis on synthetic polymer-based delivery systems.

PMID- 16952276
TI  - Lovastatin inhibits the extracellular-signal-regulated kinase pathway in
      immortalized rat brain neuroblasts.
AB  - We have shown previously that lovastatin, a 3-hydroxy-3-methyl- glutaryl coenzyme
      A reductase inhibitor, induces apoptosis in spontaneously immortalized rat brain
      neuroblasts. In the present study, we analysed the intracellular signal
      transduction pathways by which lovastatin induces neuroblast apoptosis. We showed
      that lovastatin efficiently inhibited Ras activation, which was associated with a
      significant decrease in ERK1/2 (extracellular-signal-regulated kinase 1/2)
      phosphorylation. Lovastatin also decreased CREB phosphorylation and CREB-mediated
      gene expression. The effects of lovastatin on the Ras/ERK1/2/CREB pathway were
      time- and concentration-dependent and fully prevented by mevalonate. In addition,
      we showed that two MEK [MAPK (mitogen-activated protein kinase)/ERK kinase]
      inhibitors, PD98059 and PD184352, were poor inducers of apoptosis in serum
      treated neuroblasts. However, these inhibitors significantly increased apoptosis
      induced by lovastatin treatment. Furthermore, we showed that pharmacological
      inhibition of both MEK and phosphoinositide 3-kinase activities was able to
      induce neuroblast apoptosis with similar efficacy as lovastatin. Our results
      suggest that lovastatin triggers neuroblast apoptosis by regulating several
      signalling pathways, including the Ras/ERK1/2 pathway. These findings might also
      contribute to elucidate the intracellular mechanisms involved in the central
      nervous system side effects associated with statin therapy.

PMID- 16952277
TI  - Pharmacological profiling of the Dictyostelium adenylate cyclases ACA, ACB and
      ACG.
AB  - Intracellular and secreted cAMPs play crucial roles in controlling cell movement
      and gene regulation throughout development of the social amoeba Dictyostelium
      discoideum. cAMP is produced by three structurally distinct ACs (adenylate
      cyclases), ACA, ACG and ACB, which have distinctive but overlapping patterns of
      expression and, as concluded from gene disruption studies, seemingly overlapping
      functions. In addition to gene disruption, acute pharmacological abrogation of
      protein activity can be a powerful tool to identify the protein's role in the
      biology of the organism. We analysed the effects of a range of compounds on the
      activity of ACA, ACB and ACG to identify enzyme-specific modulators. Caffeine,
      which was previously used to specifically block ACA function, also inhibited cAMP
      accumulation by ACB and ACG. IPA (2',3'-O-isopropylidene adenosine) specifically
      inhibits ACA when measured in intact cells, without affecting ACB or ACG. All
      three enzymes are inhibited by the P-site inhibitor DDA (2',5'-dideoxyadenosine)
      when assayed in cell lysates, but not in intact cells. Tyrphostin A25 [alpha
      cyano-(3,4,5-trihydroxy)cinnamonitrile] and SQ22536 [9-(tetrahydro-2'
      furyl)adenine] proved to be effective and specific inhibitors for ACG and ACA
      respectively. Both compounds acted directly on enzyme activity assayed in cell
      lysates, but only SQ22536 was also a specific inhibitor when added to intact
      cells.

PMID- 16952278
TI  - 15-deoxyspergualin inhibits eukaryotic protein synthesis through eIF2alpha
      phosphorylation.
AB  - DSG (15-deoxyspergualin), an immunosuppressant with tumoricidal properties, binds
      potently to the regulatory C-terminal 'EEVD' motif of Hsps (heat-shock proteins).
      In the present study we demonstrate that DSG inhibits eukaryotic protein
      synthesis by sequestering Hsp70 which is required for maintaining HRI (haem
      regulated inhibitor), a kinase of the eIF2alpha (eukaryotic initiation factor
      2alpha), inactive. DSG stalled initiation of protein synthesis through
      phosphorylation of HRI and eIF2alpha. Addition of a recombinant eIF2alpha (S51A)
      protein, which lacks the phosphorylation site, lowered the inhibitory potential
      of DSG in reticulocyte lysate. The inhibitory effect of DSG was also attenuated
      in HRI knockdown cells. Moreover, exogenous addition of Hsp70 or the peptide
      'EEVD' reversed the inhibitory effect of DSG. Interestingly, the inhibitory
      effect of DSG in different mammalian cancer cells was found to negatively
      correlate with the amount of Hsp70 expressed in the cells, emphasizing the link
      with Hsp70 in DSG inhibition of eukaryotic translation.

PMID- 16952279
TI  - Studies on the activity of the hypoxia-inducible-factor hydroxylases using an
      oxygen consumption assay.
AB  - The activity and levels of the metazoan HIF (hypoxia-inducible factor) are
      regulated by its hydroxylation, catalysed by 2OG (2-oxoglutarate)- and Fe(II)
      dependent dioxygenases. An oxygen consumption assay was developed and used to
      study the relationship between HIF hydroxylase activity and oxygen concentration
      for recombinant forms of two human HIF hydroxylases, PHD2 (prolyl hydroxylase
      domain-containing protein 2) and FIH (factor inhibiting HIF), and compared with
      two other 2OG-dependent dioxygenases. Although there are caveats on the absolute
      values, the apparent K(m) (oxygen) values for PHD2 and FIH were within the range
      observed for other 2OG oxygenases. Recombinant protein substrates were found to
      have lower apparent K(m) (oxygen) values compared with shorter synthetic peptides
      of HIF. The analyses also suggest that human PHD2 is selective for fragments of
      the C-terminal over the N-terminal oxygen-dependent degradation domain of HIF
      1alpha. The present results, albeit obtained under non-physiological conditions,
      imply that the apparent K(m) (oxygen) values of the HIF hydroxylases enable them
      to act as oxygen sensors providing their in vivo capacity is appropriately
      matched to a hydroxylation-sensitive signalling pathway.

PMID- 16952280
TI  - Body mass index and gastroesophageal reflux disease: a systematic review and meta
      analysis.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) is a common cause of morbidity
      and health-care utilization in many countries. Obesity is a potentially
      modifiable risk factor, but existing studies have conflicting results, possibly
      due to differences in study design, definitions, or populations. METHODS: We
      performed a systematic review and meta-analysis of studies identified using
      MEDLINE, the Web of Science electronic database, manual literature review, and a
      review of expert bibliographies. Studies were included if they: (1) evaluated
      obesity, body mass index (BMI), or another measure of body size; (2) included
      data on reflux symptoms, esophagitis, or a GERD-related hospitalization; and (3)
      reported a relative risk or odds ratio (OR) with confidence intervals or provided
      sufficient data to permit their calculation. RESULTS: We identified 20 studies
      that included 18,346 patients with GERD. Studies from the United States
      demonstrated an association between increasing BMI and the presence of GERD (95%
      confidence interval [CI]= 1.36-1.80, overweight, OR = 1.57, P value homogeneity =
      0.51, 95% CI = 1.89-2.45, obese, OR = 2.15, P= 0.10). Studies from Europe
      provided heterogeneous results despite stratification for several factors;
      individual studies demonstrated both positive associations and no association.
      CONCLUSIONS: This analysis demonstrates a positive association between increasing
      BMI and the presence of GERD within the United States; this relationship became
      apparent only after stratification by country and level of BMI. These results
      support the evaluation of weight reduction as a potential therapy for GERD.
      Further studies are needed to evaluate potential mechanisms and any differences
      in this relationship among different study populations.

PMID- 16952281
TI  - The evolving role of leptin and adiponectin in chronic liver diseases.
AB  - Leptin and adiponectin, the main metabolic products of adipose tissue, have been
      implicated in a wide spectrum of human diseases. Given the frequent presence of
      hepatic steatosis in several chronic liver diseases, there is currently
      increasing interest in the role of these adipokines in the development of hepatic
      steatosis and also in necroinflammation and fibrosis, mostly in patients with
      nonalcoholic fatty liver disease or chronic hepatitis C. According to
      experimental data, reduced adiponectin levels and increased leptin levels
      associated with leptin resistance, which are usually observed in obese patients
      with or without metabolic syndrome, may result in fat accumulation in the liver
      and in the enhancement of liver inflammation and mostly fibrogenesis. Increased
      leptin and decreased adiponectin serum levels have been detected initially in
      patients with nonalcoholic steatohepatitis and more recently in patients with
      chronic hepatitis C compared to healthy controls in most but not all studies,
      while the data on the associations between these adipokine levels and the
      severity of hepatic steatosis or fibrosis are still rather conflicting. However,
      several potential confounding parameters were not evaluated in all studies.
      Therefore, the associations between adipokines and liver histological lesions and
      their effects on liver cells should be evaluated further in prospective,
      carefully designed studies, including larger cohorts of patients with detailed
      assessment of metabolic and other potential confounding factors.

PMID- 16952282
TI  - Diagnostic precision of anti-Saccharomyces cerevisiae antibodies and perinuclear
      antineutrophil cytoplasmic antibodies in inflammatory bowel disease.
AB  - AIMS: The aim of this study was to assess the diagnostic precision of
      antiSaccharomyces cerevisiae (ASCA) and perinuclear antineutrophil cytoplasmic
      antibodies (pANCA) in inflammatory bowel disease (IBD) and evaluate their
      discriminative ability between ulcerative colitis (UC) and Crohn's disease (CD).
      METHODS: Meta-analysis of studies reporting on ASCA and pANCA in IBD was
      performed. Sensitivity, specificity, and likelihood ratios (LR+, LR-) were
      calculated for different test combinations for CD, UC, and for IBD compared with
      controls. Meta-regression was used to analyze the effect of age, DNAse, colonic
      CD, and assay type. RESULTS: Sixty studies comprising 3,841 UC and 4,019 CD
      patients were included. The ASCA+ with pANCA- test offered the best sensitivity
      for CD (54.6%) with 92.8% specificity and an area under the ROC (receiver
      operating characteristic) curve (AUC) of 0.85 (LR+ = 6.5, LR- = 0.5). Sensitivity
      and specificity of pANCA+ tests for UC were 55.3% and 88.5%, respectively (AUC of
      0.82; LR+ = 4.5, LR- = 0.5). Sensitivity and specificity were improved to 70.3%
      and 93.4% in a pediatric subgroup when combined with an ASCA- test. Meta
      regression analysis showed decreased diagnostic precision of ASCA for isolated
      colonic CD (RDOR = 0.3). CONCLUSIONS: ASCA and pANCA testing are specific but not
      sensitive for CD and UC. It may be particularly useful for differentiating
      between CD and UC in the pediatric population.

PMID- 16952283
TI  - Magnitude and economic impact of inappropriate use of stress ulcer prophylaxis in
      non-ICU hospitalized patients.
AB  - BACKGROUND: Although administration of stress ulcer prophylaxis (SUP) has been
      recommended for specific patients in the intensive care unit (ICU) setting, this
      practice has been extrapolated to care of non-ICU patients without evidence to
      support need or efficacy. AIMS: To examine the practice of SUP in non-ICU
      patients in a university hospital setting, with specific attention to resource
      utilization. METHODS: Retrospective chart review of adult non-ICU admissions to
      one family medicine and five general internal medicine teaching services over a
      consecutive 4-month period. Proportion of patients prescribed SUP was ascertained
      after exclusion of patients admitted on antisecretory therapy (AST) or prescribed
      AST for non-SUP indications. Annual cost estimates were calculated assuming full
      compliance. RESULTS: Of 1,769 patient admissions, 22% received SUP and 54% of
      these were discharged home on AST. None of these patients met evidence-based
      criteria for appropriate SUP. Inpatient SUP cost Dollars 11,024 over the 4 months
      of the study (Dollars 44,096 annually), and outpatient costs based on discharge
      prescriptions were Dollars 16,924 (Dollars 67,695 annually), yielding a total
      cost expenditure of Dollars 27,948 (Dollars 111,791 annually). CONCLUSION: SUP is
      overutilized in the non-ICU setting, and patients are often discharged
      unnecessarily on AST, resulting in significant cost expenditure. Interventions to
      ensure appropriate use of SUP should decrease resource expenditures without
      detrimental impact on quality of care.

PMID- 16952284
TI  - Public speaking stress-induced neuroendocrine responses and circulating immune
      cell redistribution in irritable bowel syndrome.
AB  - OBJECTIVES: Augmented neuroendocrine stress responses and altered immune
      functions may play a role in the manifestation of functional gastrointestinal
      (GI) disorders. We tested the hypothesis that IBS patients would demonstrate
      enhanced psychological and endocrine responses, as well as altered stress-induced
      redistribution of circulating leukocytes and lymphocytes, in response to an acute
      psychosocial stressor when compared with healthy controls. METHODS: Responses to
      public speaking stress were analyzed in N = 17 IBS patients without concurrent
      psychiatric conditions and N = 12 healthy controls. At baseline, immediately
      following public speaking, and after a recovery period, state anxiety, acute GI
      symptoms, cardiovascular responses, serum cortisol and plasma adrenocorticotropic
      hormone (ACTH) were measured, and numbers of circulating leukocytes and
      lymphocyte subpopulations were analyzed by flow cytometry. RESULTS: Public
      speaking led to significant cardiovascular activation, a significant increase in
      ACTH, and a redistribution of circulating leukocytes and lymphocyte
      subpopulations, including significant increases in natural killer cells and
      cytotoxic/suppressor T cells. IBS patients demonstrated significantly greater
      state anxiety both at baseline and following public speaking. However,
      cardiovascular and endocrine responses, as well as the redistribution of
      circulating leukocytes and lymphocyte subpopulations after public speaking
      stress, did not differ for IBS patients compared with controls. CONCLUSIONS: In
      IBS patients without psychiatric comorbidity, the endocrine response as well as
      the circulation pattern of leukocyte subpopulations to acute psychosocial stress
      do not differ from healthy controls in spite of enhanced emotional responses.
      Future studies should discern the role of psychopathology in psychological and
      biological stress responses in IBS.

PMID- 16952285
TI  - Association of fecal incontinence with physical disability and impaired cognitive
      function.
AB  - OBJECTIVES: Fecal incontinence is a common health problem for older people and is
      associated with significant morbidity and cost. In this study, we report on the
      association of fecal incontinence with physical disability and impaired cognitive
      function in a large bi-racial population of individuals aged 65 yr and older.
      METHODS: Study subjects are participants of the Chicago Health and Aging Project
      (CHAP), an ongoing study of older Chicago residents. A total of 6,099
      participants completed the baseline in-home interview and assessments used in
      this analysis. Physical disability was assessed using a performance-based measure
      of basic physical functions and three commonly used self-report measures.
      Impaired cognitive function was assessed using a global measure of the averaged
      scores of four cognitive tests. The question used to determine the presence of
      fecal incontinence was: "In the past few months have you ever lost control of
      your bowels when you didn't want to?" RESULTS: In multiple logistic regression
      models adjusted for age, sex, and race, fecal incontinence was correlated with
      the presence of physical disability and impaired cognitive function on every
      measure. For example, using the performance-based measure of physical function,
      the odds of prevalent fecal incontinence were higher by 20% (OR 1.20, 95% CI 1.2
      1.2) for each additional unit higher on the performance score, indicating a lower
      physical performance. The prevalence odds ratio for fecal incontinence was
      decreased by 51% for each one-point increase in the global cognitive score,
      indicating higher cognitive function. We found a statistically significant
      interaction between both race and physical disability and race and impaired
      cognitive function, such that the associations were stronger in blacks than in
      non-blacks. These associations remained after further adjustment for diabetes and
      stroke, and the intake of psychoactive medications. CONCLUSION: In urban,
      community-dwelling, older adults, fecal incontinence may be more common among
      persons with physical disability and impaired cognitive function.

PMID- 16952286
TI  - Endoscopic management of biliary complications after adult living donor liver
      transplantation.
AB  - OBJECTIVES: Biliary complications are one of the important issues to be addressed
      after liver transplantation. Endoscopic management of biliary complications after
      deceased donor liver transplantation (DDLT) is widely accepted, but it remains to
      be established in patients after living donor liver transplantation (LDLT).
      Endoscopic management in LDLT patients is difficult mainly because of the
      complexity of duct-to-duct reconstruction. METHODS: A total of 174 adult LDLTs
      with duct-to-duct reconstruction were performed in our institution. Biliary
      complications developed in 53 patients (30%). Among these, 18 patients were
      referred for endoscopic management and were the subjects of the present study.
      Success rate, early morbidity, and outcome were evaluated in these 18 patients.
      RESULTS: The type of graft was the right liver in six, left liver in eight, and
      right lateral sector in four patients. Ten out of 18 patients had one biliary
      anastomosis and the remaining eight had multiple anastomoses. Six patients had a
      previous history of surgical or percutaneous intervention for biliary
      complications after LDLT. Seventeen patients had one or more biliary strictures.
      Biliary casts were found in nine patients, three of whom had concomitant bile
      leaks. Strictures were successfully treated with endoscopic balloon dilation in
      12 (71%) of the 17 patients (nasobiliary catheter placement in eight and stent
      placement in four patients). Bile leak was successfully managed in two of three
      patients. Biliary casts were removed by endoscopic papillary balloon dilation in
      eight of nine patients. Five patients with failed endoscopic therapy were
      converted to percutaneous or surgical intervention. Endoscopic-procedure-related
      cholangitis developed in one patient. During follow-up with median periods of 10
      months (range 2-20 months), four of nine patients without stent placement
      developed biliary strictures, and these were relieved by additional endoscopic
      management. CONCLUSIONS: Endoscopic approach has the potential to be a first-line
      therapy for the management of biliary complications after LDLT.

PMID- 16952288
TI  - Pancreatic involvement in von Hippel-Lindau disease: report of two cases and
      review of the literature.
AB  - BACKGROUND: Von Hippel-Lindau (VHL) disease is an autosomal dominant multicancer
      syndrome caused by the germline mutation of a tumor suppressor gene. Affected
      individuals develop benign and malignant tumors of the central nervous system,
      kidneys, adrenal glands, pancreas, and reproductive system. Although VHL disease
      is mainly diagnosed after the detection of central nervous system tumors, they
      may not always be the first presentation. CASE REPORT: We report the case of a
      patient presenting with pancreatic cysts for whom the final genetic diagnosis of
      VHL disease was formulated. During management, the use of endoscopic
      ultrasonography (EUS) proved to be valid in the characterization of the
      pancreatic lesions. Family screening also revealed the genetic mutation in the
      patient's son and imaging investigations showed the presence of multiple tumors.
      The diagnosis allowed us to plan appropriate follow-up for both, thus improving
      their life expectancy. CONCLUSIONS: Gastroenterologists should be aware of the
      frequent pancreatic involvement in VHL disease and EUS can be useful in this
      setting.

PMID- 16952289
TI  - Cholestatic jaundice and IgA nephropathy induced by OTC muscle building agent
      superdrol.
AB  - Over the counter (OTC) medicines are commonly used in the United States despite a
      lack of scientific evidence for clinical utility and toxicity associated with
      their use. A case of jaundice and IgA nephropathy as a consequence of use of a
      muscle enhancing OTC supplement that was advertised as innocuous with no hormonal
      activity is described. IgA nephropathy has not been described previously in
      association with the use of testosterone. The case highlights that, besides
      adulteration, the misrepresentation of chemicals present in OTC medications and
      supplements can create confusion and a false sense of security with their use.

PMID- 16952290
TI  - Unique expression of human papilloma virus type 5 and type 16 in esophageal
      squamous cell carcinoma-a case report.
AB  - The role of human papilloma virus (HPV) in esophageal cancers from the low
      incidence area (Western population) is unclear. We report a case of esophageal
      squamous papillomatosis associated with underlying esophageal squamous cell
      carcinoma (OSCC). The esophagectomy specimen confirmed presence of HPV-5 and HPV
      16 suggesting a viral etiology. The significance of this dual infection is not
      known, but it suggests that esophageal papillomatosis is premalignant and should
      receive regular endoscopic follow-up. This is the first report of both HPV-5 and
      HPV-16 DNA detected in an esophageal cancer occurring in the Western population.

PMID- 16952291
TI  - Identification of a novel 974C-->G nonsense mutation of the MRP2/ABCC2 gene in a
      patient with Dubin-Johnson syndrome and analysis of the effects of rifampicin and
      ursodeoxycholic acid on serum bilirubin and bile acids.
AB  - Rifampicin (RIF) and ursodeoxycholic acid (UDCA) therapies have beneficial
      effects in chronic cholestatic diseases. These may result in part from the
      induction of multidrug-resistance protein 2 (MRP2/ABCC2) expression in the liver
      and kidney. However, the precise mechanisms by which RIF and UDCA act in
      cholestasis remain unclear. In the present study, we report the effects of
      chronic administration of both drugs in a patient with Dubin-Johnson syndrome
      (DJS), an inherited autosomal recessive disorder characterized by the absence of
      functional MRP2 protein at the canalicular hepatocyte membrane. A novel 974C-->G
      nonsense mutation was identified in the MRP2 gene sequence from this patient. RIF
      induced further increase in conjugated bilirubinemia, whereas concomitant
      administration of RIF and UDCA led to a dramatic rise in serum bile acid
      concentrations. These biochemical effects, which are in marked contrast to those
      observed in cholestatic settings, were concomitant with an increased MRP3, but
      not MRP4, expression on basolateral hepatocyte membrane. Such findings highlight
      the key role of MRP2 in the pharmacological properties of RIF and UDCA and
      suggest that both drugs should be used with caution in pathologic settings in
      which MRP2 expression may be downregulated, as in advanced stage of cholestatic
      diseases.

PMID- 16952292
TI  - Public attitudes toward incentives for organ donation: a national study of
      different racial/ethnic and income groups.
AB  - Attitudes toward monetary and nonmonetary incentives for living (LD) and deceased
      donation (DD) among the U.S. general public and different racial/ethnic and
      income groups have not been systematically studied. We studied attitudes via a
      telephone questionnaire administered to persons aged 18-75 in the continental
      United States. Among 845 participants (85% of randomized households), less than
      one-fifth participants were in favor of incentives for DD (range 7-17%). Most
      persons were in favor of reimbursement of medical costs (91%), paid leave (84%)
      and priority on the waiting list (59%) for LD. African Americans and Hispanics
      were more likely than Whites to be in favor of some incentives for DD. African
      Americans were more likely than Whites to be in favor of monetary incentives for
      LD. Whites with incomes less than $20 000 were more likely than Whites with
      greater incomes to be in favor of reimbursement for deceased donors' funeral
      expenses or medical expenses. The U.S. public is not generally supportive of
      incentives for DD, but is supportive of limited incentives for LD. Racial/ethnic
      minorities are more supportive than Whites of some incentives. Persons with low
      income may be more accepting of certain monetary incentives.

PMID- 16952293
TI  - The sensitized recipient: What is to be done?

PMID- 16952294
TI  - Access to the kidney transplant wait list.
AB  - The study examines selection for kidney transplantation and determines who are
      referred, how many had contraindications and whether comorbidity indices predict
      transplant status. Of 113 consecutive adult incident end-stage renal disease
      (ESRD) patients at this single center 47 (41.6%) were referred. Using published
      guidelines, 48 (42.5%) had a specific contraindication. However 26 (23%) were
      neither referred nor had contraindications. An ESRD mortality score, acute renal
      failure status and albumin were independent predictors of referral but only the
      mortality score was predictive of contraindication status. The Charlson and ESRD
      comorbidity indices were less predictive of contraindication or referral status.
      In a comparison of patients who were Candidates (referred and no
      contraindication, n = 39) compared to those who were Neither (not referred and no
      contraindications, n = 26), age was the most discriminating factor (c = 0.99, 95%
      CI 0.97-1.00). Comorbidity and mortality indices were inferior. Neither patients
      were older (75 +/- 7 years) and had comorbidity scores that were higher than
      Candidates but similar to those with contraindications (ESRD index; Neither 3.3
      +/- 2.5, Candidate 1.4 +/- 1.8, and contraindication 4.1 +/- 3.4). Comorbitity
      indices do not help explain selection practices whereas age is an important
      discriminator. How many Neither patients would benefit from transplantation is
      not known.

PMID- 16952295
TI  - Maturation-resistant dendritic cells induce hyporesponsiveness in alloreactive
      CD45RA+ and CD45RO+ T-cell populations.
AB  - Dendritic cells (DCs) play a crucial role in the induction of antigen-specific
      immunity and tolerance. Considering in vivo application of DCs prior to human
      organ transplantation, a protocol to develop tolerogenic DCs that not only induce
      unresponsiveness in naive (CD45RA+) T cells, but also in alloreactive memory
      (CD45RO+) T cells is required. The present study shows that dexamethasone (Dex)
      alters the differentiation of human monocyte-derived DCs. DexDCs cocultured with
      allogeneic CD4+ T cells induced low proliferating and low IFNgamma producing T
      cells. This is caused by lack of both costimulation via CD28 and hampered
      production of a soluble factor, as well as additional active suppression via B7
      H1 and IL-10. T cells primed by DexDCs demonstrated hyporesponsiveness upon
      restimulation with mature DCs seemingly via the induction of anergy, since these
      cells showed no enhanced apoptosis and only a limited suppressive capacity.
      Interestingly, not only cocultures of allogeneic CD45RA+, but also of CD45RO+ T
      cells with DexDCs rendered T-cell populations hyporesponsive to restimulation
      with mature DCs. The finding that also alloreactive memory T cells can be
      regulated supports the rationale of cell-based therapies to obtain allograft
      specific tolerance in transplant recipients.

PMID- 16952296
TI  - Ways to boost kidney transplant viability: a real need for the best use of older
      donors.
AB  - Using kidneys from expanded criteria donors (ECD) increased transplant activity
      but resulted in a reduced graft survival. The relatively poor long-term outcome
      of ECD grafts may be the consequence of an imbalance between the number of viable
      nephrons supplied and the metabolic demand of the recipient. Providing more
      nephrons by dual transplants may improve outcomes but fails, per se, to confer
      the same benefit of single transplants from young donors. A biopsy-based score
      system has been presented by a panel of pathologists to assess whether kidneys
      from donors older than 60 years still contain enough viable nephrons to be made
      available for transplantation, and whether single or dual transplantation should
      be used. Allocating kidneys from older donors to a single or dual transplant on
      the basis of this scoring system allowed achieving a graft survival similar to
      that of single transplants from ideal donors and remarkably superior to that of
      single transplants from older donors not evaluated histologically before
      implantation. Thus, preimplantation histologic evaluation maximizes the success
      of ECD transplants and protects recipients from receiving organs at increased
      risk of premature failure. This may limit the number of patients who eventually
      must resume dialysis and need second transplants.

PMID- 16952297
TI  - In vivo anergized T cells form altered immunological synapses in vitro.
AB  - T cells contact allogeneic antigen presenting cells (APCs) and assemble, at their
      contact interface, a molecular platform called the immunological synapse. Synapse
      based molecules provide directional signals for the T cell--either positive
      signals, resulting in T-cell activation, or negative signals causing T-cell
      inactivation or anergy. To better understand the molecular basis of in vivo T
      cell anergy we analyzed the contacts made between in vivo anergized T cells and
      APCs, and determined which signaling molecules were included or excluded from
      their immunological synapses. Anergy was induced in TCR transgenic mice by the
      intravenous injection of semiallogeneic donor spleen cells. T cells from
      anergized mice were mixed with APCs, the T-cell/APC synapses imaged using
      deconvolution microscopy, and their molecular compositions were determined. T
      cells from anergic mice formed unstable immunological synapses in vitro with
      allogeneic APCs and failed to recruit the signaling proteins necessary to
      initiate T-cell activation. These findings suggest that T-cell anergy induced by
      exposure to semiallogeneic donor cells is associated with defects in the earliest
      events of T-cell activation, immunological synapse formation and recruitment of
      TCR-mediated signaling proteins.

PMID- 16952298
TI  - Donor lymphoid organs are a major site of alloreactive T-cell priming following
      intestinal transplantation.
AB  - We hypothesized that lymphoid organs within intestinal allografts contribute to
      their immunogenicity. Consistent with this hypothesis recipient T cells rapidly
      migrated to the lymph nodes and Peyer's patches of syngeneic and allogeneic
      intestinal grafts such that at 24 h approximately 50% of the lymphocytes isolated
      from donor lymphoid organs were of recipient origin. However, only in the
      lymphoid organs of allografts did recipient T cells display an activated
      phenotype, proliferate and produce IFNgamma. Rejection of allogeneic intestines
      lacking lymphoid organs was dramatically impaired in splenectomized, lymph node
      deficient recipients compared to lymph node bearing, wild-type allogeneic
      intestines. This demonstrates the important role of donor lymphoid organs in the
      rejection process. Furthermore, recipient T cells proliferated more extensively
      and produced more IFNgamma in donor lymphoid organs than in recipient lymphoid
      organs, indicating that donor lymphoid organs play a dominant role in initiating
      the recipient anti-donor immune response following intestinal transplantation.

PMID- 16952299
TI  - Disparities in solid organ transplantation for ethnic minorities: facts and
      solutions.
AB  - The Diversity and Minority Affairs Committee of the American Society of
      Transplantation (AST) convened a symposium to examine organ transplantation in
      underserved and minority populations. The goals of the meeting included
      'benchmarking' of solid organ transplantation among minority populations, review
      of the epidemiology of end-organ damage, exploration of barriers to
      transplantation services and development of approaches to eliminate disparities.
      Participants noted that minority populations were more likely to be adversely
      affected by limited preventive medical care, lack of counseling regarding
      transplant options, and delays in transplant referrals for organ transplantation.
      These features largely reflect economic disadvantage as well as the reduced
      presence of minority professionals with training in transplant-related
      specialties. Participants in the conference noted that recent changes in organ
      allocation policies had improved access to minority individuals once listed for
      renal transplantation. Similar advances will be needed for other organs to
      address inequities in pretransplant care and underrepresentation of minorities
      among transplant professionals. The biologic basis of differences in transplant
      outcomes for minority recipients has not been adequately studied. Research funds
      must be targeted to address biologic mechanisms underlying disparate transplant
      outcomes including the impacts of environment, education, poverty and lifestyle
      choices.

PMID- 16952300
TI  - The value of plasma citrulline to predict mucosal injury in intestinal
      allografts.
AB  - Diagnosis of intestinal transplant rejection depends on clinical assessment,
      endoscopy and most importantly, histology of intestinal biopsies. Plasma
      citrulline levels (P-Cit) reflect functional enterocyte mass in nontransplant
      patients and have been evaluated in two small series after transplant. This study
      was designed to determine the sensitivity and specificity of P-Cit as diagnostic
      tool for allograft injury, especially to distinguish between viral enteritis and
      rejection. We prospectively collected 403 P-Cit samples within 24 h of intestinal
      biopsy in 49 patients. P-Cit levels were correlated with the mucosal damage and
      histopathological diagnoses. P-Cit levels in bowels with significant mucosal
      damage (i.e. moderate or severe rejection, viral enteritis, PTLD, ischemia
      reperfusion injury, allergic enteritis) were significantly lower than in
      intestines with no or mild injury (i.e. indeterminate or mild rejection,
      nonspecific enteritis): 22.9 +/- 15.4 versus 38 +/- 23.2 nmol/mL (p < 0.0001).
      Sensitivity and specificity of the test were 80% and 58.1% for rejection, and
      56.5% and 66% for viral enteritis, thereby unable to distinguish between both
      entities. In conclusion, P-Cit reflects the extent of mucosal injury regardless
      of the etiology, but does not seem to be a predictive marker for rejection or
      viral enteritis, as its values may decline only when diffuse mucosal damage has
      occurred.

PMID- 16952301
TI  - Preservation of bile ductules mitigates bile duct loss.
AB  - The finer branches of the biliary tree (FBBT) contain a regenerative compartment.
      We hypothesized that preservation of the FBBT together with its microvasculature
      will lead to recovery of biliary damage and prolonged preservation of bile
      ductules during the development of chronic liver allograft rejection. The
      interlobular bile ducts, portal bile ductules and extraportal biliary cells with
      and without microvessels were studied in sequential biopsies in five patients who
      fulfilled the Banff criteria of early chronic rejection (CR) (imminence group).
      Biopsies of CR patients (n = 12) served as controls. Biopsies were double
      immunostained with CD34 (microvessels) and cytokeratin 7 (biliary structures).
      Proliferation and proangiogenic activity were assessed with Ki67 and VEGF-A
      immunostaining. Severe damage of bile ducts in the imminence group did not
      progress to significant bile duct loss. This was associated with a high
      proliferative activity in all biliary structures and preservation of the
      microvascular compartment. VEGF-A expression was increased in all but the
      reperfusion biopsies. In conclusion, both regenerative activity of the FBBT and
      an intact microvascular compartment are associated with less damage of the
      biliary tree and could therefore be prerequisites for biliary regeneration.

PMID- 16952302
TI  - Routine coronary angiography in diabetic nephropathy patients before
      transplantation.
AB  - We evaluated the incidence of significant coronary artery stenoses (CAS), angina
      pectoris (AP), revascularization and associated risk factors in 155 consecutive
      diabetic nephropathy transplant candidates. Kidney and kidney-pancreas transplant
      candidates with diabetes for more than 10 years and/or retinopathy and/or biopsy
      verified diabetic nephropathy were included. The inclusion period was 1999-2004.
      Seventy-two percent of patients were male. Sixty-one percent had type 1 diabetes
      and 39% had type 2 diabetes and mean age was 46 years (+/-10) and 58 years (+/
      11), respectively. History of heart disease was present in 34% of patients, 34%
      had cerebro-vascular and/or peripheral atherosclerotic disease, and 51% had
      neither. Fifty-five percent had a smoking history and 46% were on dialysis.
      Significant CAS was found in 45% of patients, of whom 17% had AP. No patients
      below 35 years of age had significant CAS (n = 11, p = 0.001). Revascularization
      was performed in 57% of patients with significant CAS. The only risk factor for
      significant CAS in multiple logistic regression was age (p = 0.046).
      Approximately half of the patients had significant CAS, and half of these
      underwent revascularization. Most patients with CAS did not have symptoms of
      myocardial ischemia. The data justify screening diabetic nephropathy transplant
      candidates with coronary angiography before transplantation.

PMID- 16952303
TI  - Multiple tumor suppressor genes are increasingly methylated with age in non
      neoplastic gastric epithelia.
AB  - A number of tumor suppressor and tumor-related genes are silenced by promoter
      hypermethylation in gastric cancer. Hypermethylation is not restricted to cancer
      cells, but is also present in non-neoplastic cells during aging. Such age-related
      methylation in non-neoplastic gastric epithelia is postulated to constitute a
      field defect that increases the risk for development of gastric cancer. To
      quantitatively evaluate age-related methylation in non-neoplastic gastric
      epithelia, we used a fiber-type DNA microarray on which methylated and
      unmethylated sequence probes were mounted. After bisulfite modification, a part
      of the promoter CpG island of four tumor suppressor genes, lysyl oxidase (LOX),
      p16, RUNX3 and tazarotene-induced gene 1 (TIG1), were amplified by PCR using Cy5
      end labeled primers. Methylation rates (MRs) were calculated as the ratio of the
      fluorescence intensity of a methylated sequence probe to the total fluorescence
      intensity of methylated and unmethylated probes. Non-neoplastic gastric mucosa
      was obtained from 24 non-cancer-bearing stomachs at autopsy. MRs ranged from 0.0%
      to 77.2% (mean, 15.8%) for LOX, 0.0% to 45.8% (mean, 10.0%) for p16, 0.0% to
      83.8% (mean, 9.0%) for RUNX3, and 0.0% to 46.1% (mean, 6.6%) for TIG1, and
      significantly correlated with aging (P < 0.01). The regression curves were: y =
      0.013x(2) - 0.6184x + 4.0512, R(2) = 0.5728 (P < 0.001) for LOX; y = 0.0107x(2) -
      0.6055x + 5.2943, R(2) = 0.7891 (P < 0.00001) for p16; y = 0.0182x(2) - 1.2234x +
      11.566, R(2) = 0.5595 (P < 0.001) for RUNX3; and y = 0.0068 x(2) - 0.3586 x +
      2.4306, R(2) = 0.4670 (P < 0.01) for TIG1. Thus, our present results are
      consistent with the notion that age-related methylation is associated with cancer
      susceptibility in the elderly. Quantitative analysis of DNA methylation using DNA
      microarrays is a promising method for risk assessment in the development of
      gastric cancer.

PMID- 16952304
TI  - CCR4 as a novel molecular target for immunotherapy of cancer.
AB  - Leukocyte trafficking, which is critically regulated by chemokines and their
      receptors, shares many of the characteristics of tumor cell infiltration and
      metastasis. Expression of CC chemokine receptor 4 (CCR4) by tumor cells is
      associated with skin involvement, but CCR4 also has an important role in normal
      and tumor immunity. In a subset of patients with CCR4(+) T-cell
      leukemia/lymphoma, the tumor cells themselves function as regulatory T (Treg)
      cells, contributing to tumor survival in the face of host antitumor immune
      responses. In other types of cancers, the chemokines TARC/CCL17 and MDC/CCL22,
      specific ligands for CCR4 that are produced by tumor cells and the tumor
      microenvironment, attract CCR4(+) Treg cells to the tumor, where they create a
      favorable environment for tumor escape from host immune responses. A novel
      humanized anti-CCR4 monoclonal antibody (mAb) has been developed, the Fc region
      of which is defucosylated to enhance antibody-dependent cellular cytotoxicity by
      increasing its binding affinity to Fc receptor on effector cells. We are now
      conducting a phase I clinical trial of this anti-CCR4 mAb in patients with
      CCR4(+) T-cell leukemia/lymphoma in Japan (clinical trials gov. identifier:
      NCT00355472). Anti-CCR4 mAb could be an ideal treatment modality for many
      different cancers, not only to directly kill the CCR4(+) tumor cells, but also to
      overcome the suppressive effect of CCR4(+) Treg cells on the host immune response
      to tumor cells.

PMID- 16952305
TI  - Interleukin-12-responding asialoGM1+CD8+ central memory-type T cells as precursor
      cells for interferon-gamma-producing killer T cells.
AB  - While investigating CD8(+) memory T cells in unimmunized C57BL/6 mice, we found
      that there were unique memory-type CD8(+) T cells expressing asialoGM1 (ASGM1),
      CD62L and CCR7 cell surface molecules, which occupied approximately 10% of CD8(+)
      T cells and 35% of CD44(+) memory CD8(+) T cells. Culture of freshly isolated
      ASGM1(+)CD8(+) T cells with interleukin (IL)-12 plus IL-2 caused the
      proliferation and generation of killer T cells. Moreover, ASGM1(+)CD8(+) T cells,
      but not ASGM1(-)CD8(+) T cells, produced high levels of interferon (IFN)-gamma in
      response to IL-12 plus IL-2. Although ASGM1(+)CD8(+) T cells showed no
      significant responses to IL-12 alone or IL-2 alone, pulse incubation of
      ASGM1(+)CD8(+) T cells with IL-12 at an earlier time (0-12 h), and subsequently
      with IL-2 at a later time (12-24 h), caused the same levels of proliferation,
      killer cell generation and IFN-gamma production as when they were incubated
      simultaneously with IL-12 plus IL-2 for 24 h. Thus, ASGM1(+)CD8(+) T cells
      appeared to respond to IL-12 directly to acquire IL-2 responsiveness and
      differentiate into IFN-gamma-producing killer T cells. Indeed, freshly isolated
      ASGM1(+)CD8(+) T cells, but not ASGM1(-)CD8(+) T cells, expressed higher levels
      of IL-12R beta2 mRNA. The fact that IL-12 administration in vivo caused the
      generation of ASGM1(+)CD8(+) killer T cells in an IFN-gamma-dependent manner
      further indicated a physiological significance of ASGM1(+)CD8(+) central memory
      type T cells in IL-12-induced immunoregulation for the therapy of tumors and
      infectious diseases.

PMID- 16952306
TI  - Gender differences in health care use among the elderly population in areas of
      Norway and Finland. A cross-sectional analysis based on the HUNT study and the
      FINRISK Senior Survey.
AB  - BACKGROUND: The aim of the study was to examine gender differences in the self
      reported use of health care services by the elderly in rural and metropolitan
      areas of two Nordic countries with slightly different health care systems:
      Finland and Norway. METHODS: Population based, cross-sectional surveys conducted
      in Nord-Trondelag Norway (1995-97) and in rural and metropolitan areas of Finland
      (1997) were employed. In the Norwegian data, a total of 7,919 individuals, aged
      65-74 years old were included, and the Finnish data included 1,500 individuals.
      The outcome variables comprised whether participants had visited a general
      practitioner or a specialist, or had received hospital care or physiotherapy
      during the past 12 months. Gender differences in the use of health care services
      were analysed by multiple logistic regression, controlling for health status and
      socio-demographic characteristics. RESULTS: In Norway, elderly women visited a
      specialist or were hospitalised less often than men. In Finland, elderly women
      used all health care services except hospital care more often than men. In
      Norway, less frequent use of specialist care by women was not associated with
      self-reported health or chronic diseases. CONCLUSION: The findings revealed
      differences in self-reported use of secondary care among different genders in
      areas of Norway and Finland.

PMID- 16952307
TI  - Detection of seroconversion to West Nile virus, Usutu virus and Sindbis virus in
      UK sentinel chickens.
AB  - We previously reported evidence of West Nile virus (WNV) circulation in UK birds,
      probably introduced by migratory birds from overseas. We now demonstrate WNV
      specific seroconversion in sentinel chickens raised on an English farm. Maternal
      neutralizing antibodies to WNV in hatchlings declined within three weeks. During
      the following months, healthy chickens developed WNV neutralizing antibodies that
      were confirmed by immunoblotting and indirect immunofluorescence tests using WNV
      antigens. The proportion of seropositive chickens was higher for WNV than for
      Usutu virus or Sindbis virus. Attempts to isolate infectious virus or to detect
      viral RNA in the sera, failed.

PMID- 16952308
TI  - Human papillomavirus in amniotic fluid.
AB  - BACKGROUND: There is evidence to suggest that human papillomavirus (HPV) can
      cross the placenta resulting in in-utero transmission. The goal of this study was
      to determine if HPV can be detected in amniotic fluid from women with intact
      amniotic membranes. METHODS: Residual amniotic fluid and cultured cell pellets
      from amniocentesis performed for prenatal diagnosis were used. PGMY09/11 L1
      consensus primers and GP5+/GP6+ primers were used in a nested polymerase chain
      reaction assay for HPV. RESULTS: There were 146 paired samples from 142 women
      representing 139 singleton pregnancies, 2 twin pregnancies, and 1 triplet
      pregnancy. The women were 78% Caucasian, 5% African American, 14% Asian, and 2%
      Hispanic. The average age was 35.2 years with a range of 23-55 years. All samples
      were beta-globin positive. HPV was not detected in any of the paired samples.
      CONCLUSION: Given the age range, race, and ethnicity of the study population, one
      would anticipate some evidence of HPV if it could easily cross the placenta, but
      there was none.

PMID- 16952309
TI  - Staphylococcus aureus enterotoxins induce IL-8 secretion by human nasal
      epithelial cells.
AB  - BACKGROUND: Staphylococcus aureus produces a set of proteins which act both as
      superantigens and toxins. Although their mode of action as superantigens is well
      understood, little is known about their effects on airway epithelial cells.
      METHODS: To investigate this problem, primary nasal epithelial cells derived from
      normal and asthmatic subjects were stimulated with staphylococcal enterotoxin A
      and B (SEA and SEB) and secreted (supernatants) and cell-associated (cell
      lysates) IL-8, TNF-alpha, RANTES and eotaxin were determined by specific ELISAs.
      RESULTS: Non-toxic concentrations of SEA and SEB (0.01 microg/ml and 1.0
      microg/ml) induced IL-8 secretion after 24 h of culture. Pre-treatment of the
      cells with IFN-gamma (50 IU/ml) resulted in a further increase of IL-8 secretion.
      In cells from healthy donors pretreated with IFN-gamma, SEA at 1.0 mug/ml induced
      release of 1009 pg/ml IL-8 (733.0-1216 pg/ml, median (range)) while in cells from
      asthmatic donors the same treatment induced significantly higher IL-8 secretion -
      1550 pg/ml (1168.0-2000.0 pg/ml p = 0.04). Normal cells pre-treated with IFN
      gamma and then cultured with SEB at 1.0 mug/ml released 904.6 pg/ml IL-8 (666.5
      1169.0 pg/ml). Cells from asthmatics treated in the same way produced
      significantly higher amounts of IL-8--1665.0 pg/ml (1168.0-2000.0 pg/ml, p =
      0.01). Blocking antibodies to MHC class II molecules added to cultures stimulated
      with SEA and SEB, reduced IL-8 secretion by about 40% in IFN-gamma unstimulated
      cultures and 75% in IFN-gamma stimulated cultures. No secretion of TNF-alpha,
      RANTES and eotaxin was noted. CONCLUSION: Staphylococcal enterotoxins may have a
      role in the pathogenesis of asthma.

PMID- 16952310
TI  - Nutritional therapy and infectious diseases: a two-edged sword.
AB  - The benefits and risks of nutritional therapies in the prevention and management
      of infectious diseases in the developed world are reviewed. There is strong
      evidence that early enteral feeding of patients prevents infections in a variety
      of traumatic and surgical illnesses. There is, however, little support for
      similar early feeding in medical illnesses. Parenteral nutrition increases the
      risk of infection when compared to enteral feeding or delayed nutrition. The use
      of gastric feedings appears to be as safe and effective as small bowel feedings.
      Dietary supplementation with glutamine appears to lower the risk of post-surgical
      infections and the ingestion of cranberry products has value in preventing
      urinary tract infections in women.

PMID- 16952311
TI  - Comparison of chromosomal and array-based comparative genomic hybridization for
      the detection of genomic imbalances in primary prostate carcinomas.
AB  - BACKGROUND: In order to gain new insights into the molecular mechanisms involved
      in prostate cancer, we performed array-based comparative genomic hybridization
      (aCGH) on a series of 46 primary prostate carcinomas using a 1 Mbp whole-genome
      coverage platform. As chromosomal comparative genomic hybridization (cCGH) data
      was available for these samples, we compared the sensitivity and overall
      concordance of the two methodologies, and used the combined information to infer
      the best of three different aCGH scoring approaches. RESULTS: Our data
      demonstrate that the reliability of aCGH in the analysis of primary prostate
      carcinomas depends to some extent on the scoring approach used, with the
      breakpoint estimation method being the most sensitive and reliable. The pattern
      of copy number changes detected by aCGH was concordant with that of cCGH, but the
      higher resolution technique detected 2.7 times more aberrations and 15.2% more
      carcinomas with genomic imbalances. We additionally show that several aberrations
      were consistently overlooked using cCGH, such as small deletions at 5q, 6q, 12p,
      and 17p. The latter were validated by fluorescence in situ hybridization
      targeting TP53, although only one carcinoma harbored a point mutation in this
      gene. Strikingly, homozygous deletions at 10q23.31, encompassing the PTEN locus,
      were seen in 58% of the cases with 10q loss. CONCLUSION: We conclude that aCGH
      can significantly improve the detection of genomic aberrations in cancer cells as
      compared to previously established whole-genome methodologies, although
      contamination with normal cells may influence the sensitivity and specificity of
      some scoring approaches. Our work delineated recurrent copy number changes and
      revealed novel amplified loci and frequent homozygous deletions in primary
      prostate carcinomas, which may guide future work aimed at identifying the
      relevant target genes. In particular, biallelic loss seems to be a frequent
      mechanism of inactivation of the PTEN gene in prostate carcinogenesis.

PMID- 16952312
TI  - Growing PET positive nodule in a patient with histoplasmosis: case report.
AB  - BACKGROUND: Pulmonary histoplasmosis is a mycotic infection that often resembles
      pulmonary malignancy and continues to complicate the evaluation of pulmonary
      nodules. CASE PRESENTATION: We report a case of an immunocompetent patient who,
      despite adequate treatment for known histoplasmosis lung infection, presented
      with radiological and F-18 fluorodeoxyglucose (FDG) positron emission tomography
      (PET) findings mimicking primary lung malignancy which eventually required
      surgical resection. CONCLUSION: Histoplasmosis infection may radiologically
      resemble pulmonary malignancy, often causing a diagnostic dilemma. PET imaging is
      currently used for and considered accurate in the evaluation of pulmonary
      nodules. However, overlap in PET standardized uptake value (SUV) between
      granulomatous and malignant lesions decreases the accuracy of PET as a diagnostic
      modality. Future advances in PET imaging are needed to improve its accuracy in
      the evaluation of pulmonary nodules in areas where histoplasmosis is endemic.

PMID- 16952313
TI  - Fatty tissue within the maxillary sinus: a rare finding.
AB  - BACKGROUND: We report a rare case of fatty tissue within the maxillary sinus in a
      21-year-old woman, with a history of several previous punctures of the maxillary
      sinus. CASE PRESENTATION: Clinical data of the patient was analysed
      retrospectively. The patient presented with symptoms of left-sided chronic
      maxillary sinusitis and had undergone several punctures of the left maxillary
      sinus 18 months earlier. Subsequent to one of the procedures an acute pain in the
      left orbit lasting a couple of days was noted. Left endoscopic transnasal
      antrotomy was performed. The maxillary sinus was filled with polypous,
      chronically inflamed mucous membrane. Upon its removal, the maxillary roof was
      identified as drawn downwards and covered with normal mucous membrane. Upon
      dissection of the membrane, adipose tissue filling the zygomatic recess of the
      sinus was identified and subsequently removed. The maxillary roof was unchanged.
      Histopathologic examination confirmed the material to be adipose tissue. No short
      or long term sequelae occurred. CONCLUSION: Adipose tissue can be found in the
      maxillary sinus most commonly when penetrating from surrounding locations. It is
      our hypothesis that in the reported patient it penetrated from the orbit to the
      maxillary sinus following puncture. It seems that a hole in the maxillary sinus
      roof, about 1 mm in diameter, caused by the needle, may have been a portal of
      entry for the adipose tissue into the maxillary sinus. The discussed case
      suggests particular care be taken in performing puncture of the maxillary sinus.

PMID- 16952315
TI  - A prospective study of differences in duodenum compared to remaining small bowel
      motion between radiation treatments: implications for radiation dose escalation
      in carcinoma of the pancreas.
AB  - PURPOSE: As a foundation for a dose escalation trial, we sought to characterize
      duodenal and non-duodenal small bowel organ motion between fractions of
      pancreatic radiation therapy. PATIENTS AND METHODS: Nine patients (4 women, 5
      men) undergoing radiation therapy were enrolled in this prospective study. The
      patients had up to four weekly CT scans performed during their course of
      radiation therapy. Pancreas, duodenum and non-duodenal small bowel were then
      contoured for each CT scan. On the initial scan, a four-field plan was generated
      to fully cover the pancreas. This plan was registered to each subsequent CT scan.
      Dose-volume histogram (DVH) analyses were performed for the duodenum, non
      duodenal small bowel, large bowel, and pancreas. RESULTS: With significant
      individual variation, the volume of duodenum receiving at least 80% of the
      prescribed dose was consistently greater than the remaining small bowel. In the
      patient with the largest inter-fraction variation, the fractional volume of non
      duodenal small bowel irradiated to at least the 80% isodose line ranged from 1%
      to 20%. In the patient with the largest inter-fraction variation, the fractional
      volume of duodenum irradiated to at least the 80% isodose line ranged from 30% to
      100%. CONCLUSION: The volume of small bowel irradiated during four-field
      pancreatic radiation therapy changes substantially between fractions. This
      suggests dose escalation may be possible. However, dose limits to the duodenum
      should be stricter than for other segments of small bowel.

PMID- 16952314
TI  - High degree of conservancy among secreted salivary gland proteins from two
      geographically distant Phlebotomus duboscqi sandflies populations (Mali and
      Kenya).
AB  - BACKGROUND: Salivary proteins from sandflies are potential targets for
      exploitation as vaccines to control Leishmania infection; in this work we tested
      the hypothesis that salivary proteins from geographically distant Phlebotomus
      duboscqi sandfly populations are highly divergent due to the pressure exerted by
      the host immune response. Salivary gland cDNA libraries were prepared from wild
      caught P. duboscqi from Mali and recently colonised flies of the same species
      from Kenya. RESULTS: Transcriptome and proteome analysis resulted in the
      identification of the most abundant salivary gland-secreted proteins. Orthologues
      of these salivary proteins were identified by phylogenetic tree analysis.
      Moreover, comparative analysis between the orthologues of these two different
      populations resulted in a high level of protein identity, including the predicted
      MHC class II T-cell epitopes from all these salivary proteins. CONCLUSION: These
      data refute the hypothesis that salivary proteins from geographically distinct
      populations of the same Phlebotomus sandfly species are highly divergent. They
      also suggest the potential for using the same species-specific components in a
      potential vector saliva-based vaccine.

PMID- 16952316
TI  - Interferon-beta1a reduces plasma CD31+ endothelial microparticles (CD31+EMP) in
      multiple sclerosis.
AB  - BACKGROUND: A correlation between plasma CD31+ endothelial microparticles
      (CD31+EMP) levels and clinical, as well as brain MRI activity, in multiple
      sclerosis (MS) patients has been previously reported. However, the effect(s) of
      treatment with interferon-beta1a (IFN-beta1a) on plasma levels of CD31+EMP has
      not been assessed. In a prospective study, we measured plasma CD31+EMP levels in
      30 patients with relapsing-remitting MS. METHODS: Using flow cytometry, in a
      blinded study, we measured plasma CD31+EMP in 30 consecutive patients with
      relapsing-remitting MS (RRMS) prior to and 4, 12, 24 and 52 weeks after
      initiation of intramuscular therapy with interferon-beta1a (IFN-beta1a), 30
      micrograms weekly. At each visit, clinical examination was performed and expanded
      disability status scale (EDSS) scores were assessed. RESULTS: Plasma levels of
      CD31+EMP were significantly reduced from 24 through 52 weeks following initiation
      of treatment with IFN-beta1a. CONCLUSION: Our data suggest that serial
      measurement of plasma CD31+EMP levels may be used as a surrogate marker of
      response to therapy with INF-beta1a. In addition, the decline in plasma levels of
      CD31+EMP further supports the concept that IFN-beta1a exerts stabilizing effect
      on the cerebral endothelial cells in pathogenesis of MS.

PMID- 16952317
TI  - Efficient pairwise RNA structure prediction and alignment using sequence
      alignment constraints.
AB  - BACKGROUND: We are interested in the problem of predicting secondary structure
      for small sets of homologous RNAs, by incorporating limited comparative sequence
      information into an RNA folding model. The Sankoff algorithm for simultaneous RNA
      folding and alignment is a basis for approaches to this problem. There are two
      open problems in applying a Sankoff algorithm: development of a good unified
      scoring system for alignment and folding and development of practical heuristics
      for dealing with the computational complexity of the algorithm. RESULTS: We use
      probabilistic models (pair stochastic context-free grammars, pairSCFGs) as a
      unifying framework for scoring pairwise alignment and folding. A constrained
      version of the pairSCFG structural alignment algorithm was developed which
      assumes knowledge of a few confidently aligned positions (pins). These pins are
      selected based on the posterior probabilities of a probabilistic pairwise
      sequence alignment. CONCLUSION: Pairwise RNA structural alignment improves on
      structure prediction accuracy relative to single sequence folding. Constraining
      on alignment is a straightforward method of reducing the runtime and memory
      requirements of the algorithm. Five practical implementations of the pairwise
      Sankoff algorithm - this work (Consan), David Mathews' Dynalign, Ian Holmes'
      Stemloc, Ivo Hofacker's PMcomp, and Jan Gorodkin's FOLDALIGN - have comparable
      overall performance with different strengths and weaknesses.

PMID- 16952318
TI  - Insights into age- and sickle-cell-disease-interaction using principal components
      analysis.
AB  - BACKGROUND: In the context of sickle cell anemia, peripheral blood indexes
      provide key information that is also potentially influenced by age. Therefore, it
      is necessary to understand the extent and nature of interactions between sickle
      cell anemia and age, especially in situations where there is a high prevalence of
      sickle cell anemia. METHODS: In a cross-sectional study of 374 subjects with
      varying hemoglobin S (HbS) status, we characterized the interaction between age
      and sickle hemoglobin using principal components analysis. RESULTS: Factor
      analysis in subjects with hemoglobin AA identified three orthogonal factors-
      normal erythropoiesis, presence of thalassemia and the aggregability potential of
      the blood. These three factors were differentially associated with hemoglobin
      status. Age influenced the association of factors #2 and #3 with hemoglobin
      status. CONCLUSION: Our findings suggest that the interaction between age and
      hemoglobin status needs to be considered in both clinical and public health
      settings.

PMID- 16952319
TI  - Functional assessment of older patients in the emergency department: comparison
      between standard instruments, medical records and physicians' perceptions.
AB  - BACKGROUND: We evaluated the accuracy of physician recognition of functional
      status impairment in older emergency departments (ED) patients. In particular, we
      evaluated the accuracy of medical records (a comparison of the information in the
      medical record with the functional status based on proxy interviews), and the
      accuracy of physician knowledge (a comparison of the information obtained from
      the responsible physician with the functional status based on proxy interviews).
      METHODS: Cross-sectional study on 101 frail older patients selected at random
      from among those attending ED, their ED physicians, and respondents. The study
      was conducted at ED in four general university teaching hospitals in a city, from
      July through November 2003. Functional data shown on patients' medical records
      were compared against functional data obtained from respondents (family members),
      using Kendall's Tau-b statistic. In addition patients' Katz Indices (which
      assesses six basic activities of daily living--basic ADL) based on interviews
      with ED physicians were compared against those obtained from respondents, using
      the coefficient of concordance weighted kappa (kappa). Each patient and his
      respondent were paired with a single physician. RESULTS: The correlation between
      information on dependence for basic ADL obtained from medical records and that
      furnished by respondents, was 0.41 (95% CI 0.27-0.55). Concordance between the
      respective Katz Indices obtained from physicians and respondents was 0.47 (95% CI
      0.38-0.57). CONCLUSION: Older subjects' functional status is not properly
      assessed by emergency department physicians.

PMID- 16952320
TI  - IL-1 does not reverse the anti-proliferative effect of aspirin in breast cancer
      cells.
AB  - OBJECTIVES: Interleukin-1 (IL-1) is a multifunctional proinflammatory cytokine.
      There have been studies suggesting a role in affecting growth and invasiveness of
      malignant breast cells by either blocking or stimulating growth of cultured MCF-7
      breast cancer cells. This effect may be mediated by induction of COX-2. Aspirin
      is an inhibitor of COX-2 and has been implicated, with other non-steroidal anti
      inflammatory drugs (NSAIDS) in prevention and treatment of breast cancer. In this
      study the in vitro effects of IL-1 and aspirin on growth of MCF-7 human breast
      cancer cells was examined. METHODS: MCF-7 cells were treated with various
      concentrations of IL-1 and aspirin alone and in combination. Cell growth was
      assessed by cell number measurement. RESULTS: Aspirin significantly decreased
      growth rate in a dose-dependent manner, alone and as a combined treatment with IL
      1 with a maximum reduction in growth rate at 300 mg/ml (P < 0.05). Treatment with
      IL-1 alone showed no significant effect on growth rate of MCF-7 cells (P > 0.05).
      CONCLUSION: This study confirms that aspirin suppresses the proliferation rate of
      MCF-7 cells both as a single agent and in combination with IL-1. It also suggests
      that IL-1 alone does not stimulate or inhibit growth of MCF-7 cells.

PMID- 16952321
TI  - Automatic layout and visualization of biclusters.
AB  - BACKGROUND: Biclustering has emerged as a powerful algorithmic tool for analyzing
      measurements of gene expression. A number of different methods have emerged for
      computing biclusters in gene expression data. Many of these algorithms may output
      a very large number of biclusters with varying degrees of overlap. There are no
      systematic methods that create a two-dimensional layout of the computed
      biclusters and display overlaps between them. RESULTS: We develop a novel
      algorithm for laying out biclusters in a two-dimensional matrix whose rows
      (respectively, columns) are rows (respectively, columns) of the original dataset.
      We display each bicluster as a contiguous submatrix in the layout. We allow the
      layout to have repeated rows and/or columns from the original matrix as required,
      but we seek a layout of the smallest size. We also develop a web-based search
      interface for the user to query the genes and samples of interest and visualise
      the layout of biclusters matching the queries. CONCLUSION: We demonstrate the
      usefulness of our approach on gene expression data for two types of leukaemia and
      on protein-DNA binding data for two growth conditions in Saccharomyces
      cerevisiae. The software implementing the layout algorithm is available at
      http://bioinformatics.cs.vt.edu/~murali/papers/bivoc.

PMID- 16952322
TI  - The effects of economic deprivation on psychological well-being among the working
      population of Switzerland.
AB  - BACKGROUND: The association between poverty and mental health has been widely
      investigated. There is, however, limited evidence of mental health implications
      of working poverty, despite its representing a rapidly expanding segment of
      impoverished populations in many developed nations. In this study, we examined
      whether working poverty in Switzerland, a country with substantial recent growth
      among the working poor, was correlated with two dependent variables of interest:
      psychological health and unmet mental health need. METHODS: This cross-sectional
      study used data drawn from the first 3 waves (1999-2001) of the Swiss Household
      Panel, a nationally representative sample of the permanent resident population of
      Switzerland. The study sample comprised 5453 subjects aged 20-59 years. We used
      Generalized Estimating Equation models to investigate the association between
      working poverty and psychological well-being; we applied logistic regression
      models to analyze the link between working poverty and unmet mental health need.
      Working poverty was represented by dummy variables indicating financial
      deficiency, restricted standard of living, or both conditions. RESULTS: After
      controlling other factors, restricted standard of living was significantly (p <
      .001) negatively correlated with psychological well-being; it was also associated
      with approximately 50% increased risk of unmet mental health need (OR = 1.55; 95%
      CI 1.17-2.06). CONCLUSION: The findings of this study contribute to our
      understanding of the potential psychological impact of material deprivation on
      working Swiss citizens. Such knowledge may aid in the design of community
      intervention programs to help reduce the individual and societal burdens of
      poverty in Switzerland.

PMID- 16952323
TI  - CRNPRED: highly accurate prediction of one-dimensional protein structures by
      large-scale critical random networks.
AB  - BACKGROUND: One-dimensional protein structures such as secondary structures or
      contact numbers are useful for three-dimensional structure prediction and helpful
      for intuitive understanding of the sequence-structure relationship. Accurate
      prediction methods will serve as a basis for these and other purposes. RESULTS:
      We implemented a program CRNPRED which predicts secondary structures, contact
      numbers and residue-wise contact orders. This program is based on a novel machine
      learning scheme called critical random networks. Unlike most conventional one
      dimensional structure prediction methods which are based on local windows of an
      amino acid sequence, CRNPRED takes into account the whole sequence. CRNPRED
      achieves, on average per chain, Q3 = 81% for secondary structure prediction, and
      correlation coefficients of 0.75 and 0.61 for contact number and residue-wise
      contact order predictions, respectively. CONCLUSION: CRNPRED will be a useful
      tool for computational as well as experimental biologists who need accurate one
      dimensional protein structure predictions.

PMID- 16952324
TI  - A rapid ethnographic study of breastfeeding in the North and South of Italy.
AB  - BACKGROUND: The past ten years have witnessed a rising trend in the prevalence
      and duration of breastfeeding in Italy, but breastfeeding rates increase in an
      unequal way; they are higher in the North of Italy than in the South. The purpose
      of this study was to describe the experiences, expectations and beliefs of a
      sample of mothers, and to identify differences, if any, between the North and the
      South of Italy. METHODS: The study was conducted in two regions of Italy, Friuli
      Venezia Giulia in the Northeast and Basilicata in the South. Two hundred and
      seventy-nine mothers of infants and children 6 to 23 months of age were
      interviewed using an 85-item questionnaire including closed and open questions on
      infant feeding experiences and beliefs, sources of information and support,
      reasons for intended and actual choices and practices, and some demographic and
      social variables. Face-to-face interviews were conducted between May 2001 and
      September 2002. Quantitative and qualitative methods were used for data analysis.
      RESULTS: The distribution of the mothers by age, education, employment and parity
      did not differ from that of the general population of the two regions. The
      reported rates of initiation and duration of breastfeeding were also similar: 95%
      started breastfeeding, exclusive breastfeeding was 32% at three and 9% at six
      months, with 64% and 35% of any breastfeeding, respectively. Some differences
      were reported in the rates of full breastfeeding, reflecting different ages of
      introduction of non-nutritive fluids. These, as well as nutritive fluids-
      including infant formula--and complementary foods, were introduced far too early.
      Advice on infant feeding was generally provided by health professionals and often
      was not based on up-to-date recommendations. Mothers were generally aware of the
      advantages of breastfeeding, but at the same time reported problems that they
      were not able to solve alone or through social and health system support. Most
      mothers would welcome the support of a peer counsellor. More mothers in
      Basilicata than in Friuli Venezia Giulia reported difficulties with breastfeeding
      related to returning to work and were not familiar with their rights on
      breastfeeding and maternity leave. CONCLUSION: Programmes for the protection,
      promotion and support of breastfeeding in these and similar regions of Italy
      should concentrate on better training of health professionals with regards to
      lactation management, communication, and counselling skills. The addition of
      trained peer counsellors could reinforce the work done by the health system and,
      through community involvement, could help change social prejudice in the mid- and
      long-term. The differences between regions should be taken into account in
      formulating these programmes to avoid increasing, and possibly to decrease, the
      current gaps.

PMID- 16952325
TI  - Robot-assisted radical prostatectomy in obese patients.
AB  - OBJECTIVES: Few centers perform extraperitoneal robot assisted radical
      prostatectomy. The average patient weight is increasing to the mildly obese.
      Little is known as to the difficulty-impact, obesity may have on robot-assisted
      extraperitoneal prostatectomy (RAP). We assess our own experience with obese
      patients undergoing RAP. MATERIALS AND METHODS: Information on 375 consecutive
      patients undergoing robot-assisted extraperitoneal prostatectomy by a single
      surgeon was gathered. Obesity is defined as having a body mass index (BMI)
      greater than 30 kg/m2. Patients with BMI >/= 30 were compared to those with BMI <
      30. Specific comparators between the groups were: age, total operating time,
      estimated blood loss, total prostate specific antigen (PSA), specimen weight,
      pathological stage, grade and margin, complications, and functional outcomes.
      RESULTS: Sixty-seven men were identified as obese. When comparing the two groups,
      no statistically significant difference (p > .05) was noted in operative time
      (229 versus 217 min), blood loss (205 versus 175 ml), PSA, clinical and
      pathologic stages, specimen weight, and complications. 15% of non-obese patients
      had a positive margin compared to 12% of obese patients (p > .05). The 6-month
      continence rate in patients with a BMI >/= 30 was 92% versus 97% in patients with
      a BMI < 30. CONCLUSIONS: The extraperitoneal approach to performing a robot
      assisted prostatectomy is not associated with increased morbidity in the obese
      patient. There were no statistically significant differences noted in oncological
      or functional outcomes between the two groups.

PMID- 16952326
TI  - The use of bisphosphonates in men with hormone-refractory prostate cancer: a
      systematic review of randomized trials.
AB  - PURPOSE: A systematic review of randomized controlled trials (RCTs) was performed
      to assess the benefits of bisphosphonate therapy in men with hormone-refractory
      prostate cancer (HRPC). METHODS: The literature was searched to identify RCTs or
      meta-analyses comparing treatment with bisphosphonates to placebo or no
      treatment. RESULTS: Ten trials that studied clodronate (five trials, 404
      patients), pamidronate (two trials, 350 patients), alendronate (one trial, 49
      patients), etidronate (one trial, 51 patients), and zoledronic acid (one trial,
      643 patients) in men with HRPC and bone metastases met the eligibility criteria.
      Pain response was the most frequently reported primary outcome (eight trials).
      Only the smallest trial demonstrated a statistically significant improvement in
      pain, but other non-statistically significant trends and subgroup analyses
      showing improvement in pain were observed in six clodronate and pamidronate
      trials. Three trials reported skeletal-related events (SREs). A trial studying
      zoledronic acid reported a statistically and clinically significant reduction in
      the number of patients having at least one SRE; however, there were higher rates
      of some adverse effects, and quality of life was not improved. CONCLUSION:
      Zoledronic acid appears to reduce the number of patients having at least one SRE
      in men with bone metastases from HRPC that are causing minimal or no pain. This
      benefit should be weighed against the associated toxicities, and the neutral
      effect on quality of life. Bisphosphonates may reduce bone pain in men with HRPC,
      but the evidence is less robust. Further investigations to identify the role of
      bisphosphonates alone and in combination with other therapies proven effective
      for men with HRPC are warranted.

PMID- 16952327
TI  - Treatment of BCG failures with intravesical BCG/Interferon: the University of
      Montreal experience.
AB  - OBJECTIVE: Bacillus Calmette-Guerin (BCG) has shown promise in large scale
      studies. We assessed recurrence-free survival in patients treated with
      intravesical BCG/Interferon (IFN) for non-muscle invasive, BCG refractory,
      transitional cell carcinoma (TCC) of the urinary bladder at our local
      institution. METHODS: Cancer control data were gathered for patients enrolled in
      a BCG/Interferon protocol at the University of Montreal. The main inclusion
      criteria consisted of pathologically proven evidence of intravesical BCG failure,
      and of complete transurethral resection of latest post BCG recurrence. Induction
      consisted of eight intravesical BCG/Interferon instillations. Select patients
      were treated with BCG/Interferon maintenance therapy. RESULTS: Thirteen patients
      aged from 45 to 81 years (mean: 65) were included. Stages at TCC diagnosis were
      distributed as follows: 6 (46%) CIS, 3 (23%) Ta, and 4 (31%) T1. Induction BCG
      consisted of an average of 11 weekly instillations (range 3-24). Prior to
      BCG/Interferon stage distribution was as follows: 9 (69%) CIS, and 4 (31%) T1.
      BCG/Interferon maintenance was administered to 5 (38%) patients. Follow-up ranged
      from 1.5 to 32 months (mean=15, median=12). Recurrence was diagnosed in 5
      patients (38%). Recurrence free survival (RFS) at 24 months was 66%. When
      stratified according to T stage prior to BCG/IFN, patients with CIS fared worse
      than T1 patients (50% versus 100%). Maintenance had no effect on RFS (75% versus
      69%). CONCLUSIONS: Our results corroborate previous BCG/IFN reports. In selected
      patients, intravesical BCG/IFN offers a valid alternative to definitive therapy.

PMID- 16952328
TI  - Does indigo carmine prevent early artificial urinary sphincter cuff erosion?
AB  - INTRODUCTION: Urethral erosion following artificial urinary sphincter (AUS)
      placement is hypothesized to be secondary to unrecognized intra-operative
      urethral injury. Intra-urethral indigo carmine solution (ICS), a blue dye,
      following urethral mobilization should identify intra-operative urethrotomy and
      prevent early post-operative cuff erosion. METHODS: Retrospective review was
      completed of all men undergoing AUS (AMS 800 device) insertion between January
      2000 and January 2005 for post prostatectomy stress incontinence at one
      institution. Operative reports were examined for use of intra-operative injection
      of ICS as well as documentation of urethral injury. Post-operative course was
      reviewed for evidence of early cuff erosion. All patients were followed a minimum
      of 6 months post-operatively. RESULTS: Seventy-eight men underwent AUS placement
      during the investigative period. Forty-one men received intra-operative ICS
      injection following urethral mobilization and 37 men did not. ICS identified one
      intra-operative urethral injury. No urethral injuries were noted in the non
      injection group. The ICS group suffered 3 (7.3%) early urethral erosions; the
      control group had one early urethral erosion (2.7%). CONCLUSION: Intra-operative
      ICS use is easy, safe, and able to identify urethral injury. However, its use did
      not preclude the incidence of early cuff erosion. This may postulate the
      existence of early urethral cuff erosion as a separate entity not dependent on
      intra-operative urethrotomy.

PMID- 16952329
TI  - Sclerosing mesenteritis progressing to ureteral obstruction.
AB  - Sclerosing mesenteritis is part of a spectrum of benign, inflammatory diseases of
      the abdominal mesentery. It has been called retractile mesenteritis, and other
      forms include mesenteric panniculitis and mesenteric lipodystrophy. The disease
      rarely involves the retroperitoneum. We present a case of sclerosing mesenteritis
      that progressed to ureteral involvement.

PMID- 16952330
TI  - Sarcoid of the testis.
AB  - Sarcoidosis is a chronic disease that rarely manifests in the male reproductive
      tract. Due to its infrequent nature, treatment for sarcoid of the male
      reproductive tract is controversial. We report a case of incidentally discovered
      sarcoid of the testis in a white male managed with a testis sparing approach.

PMID- 16952331
TI  - Case report: renal lymphangiectasia.
AB  - Renal lymphangiectasia is a rare renal condition. We present a case of bilateral
      renal lymphangiectasia in a 52-year-old man who presented with bilateral flank
      pain and gross hematuria. The clinical features, diagnosis and characteristic
      imaging findings are reviewed. This condition should be considered in the
      differential diagnosis of cystic renal masses in both children and adults.

PMID- 16952332
TI  - Surfaces and interfacial water: evidence that hydrophilic surfaces have long
      range impact.
AB  - It is generally thought that the impact of surfaces on the contiguous aqueous
      phase extends to a distance of no more than a few water-molecule layers. Older
      studies, on the other hand, suggest a more extensive impact. We report here that
      colloidal and molecular solutes suspended in aqueous solution are profoundly and
      extensively excluded from the vicinity of various hydrophilic surfaces. The width
      of the solute-free zone is typically several hundred microns. Such large
      exclusion zones were observed in the vicinity of many types of surface including
      artificial and natural hydrogels, biological tissues, hydrophilic polymers,
      monolayers, and ion-exchange beads, as well as with a variety of solutes. Using
      microscopic observations, as well as measurements of electrical potential and UV
      Vis absorption-spectra, infrared imaging, and NMR imaging, we find that the
      solute-free zone is a physically distinct and less mobile phase of water that can
      co-exist indefinitely with the contiguous solute-containing phase. The
      extensiveness of this modified zone is impressive, and carries broad implication
      for surface-molecule interactions in many realms, including cellular recognition,
      biomaterial-surface antifouling, bioseparation technologies, and other areas of
      biology, physics and chemistry.

PMID- 16952333
TI  - Sleep problems, comorbid mental disorders, and role functioning in the national
      comorbidity survey replication.
AB  - BACKGROUND: Little is known about the population prevalence of sleep problems or
      whether the associations of sleep problems with role impairment are due to
      comorbid mental disorders. METHODS: The associations of four 12-month sleep
      problems (difficulty initiating or maintaining sleep, early morning awakening,
      nonrestorative sleep) with role impairment were analyzed in the National
      Comorbidity Survey Replication controlling 12-month DSM-IV anxiety, mood, impulse
      control, and substance disorders. The WHO Composite International Diagnostic
      Interview was used to assess sleep problems and DSM-IV disorders. The WHO
      Disability Schedule-II (WHO-DAS) was used to assess role impairment. RESULTS:
      Prevalence estimates of the separate sleep problems were in the range 16.4-25.0%,
      with 36.3% reporting at least one of the four. Mean 12-month duration was 24.4
      weeks. All four problems were significantly comorbid with all the 12-month DMS-IV
      disorders assessed in the survey (median OR: 3.4; 25(th)-75(th) percentile: 2.8
      3.9) and significantly related to role impairment. Relationships with role
      impairment generally remained significant after controlling comorbid mental
      disorders. Nonrestorative sleep was more strongly and consistently related to
      role impairment than were the other sleep problems. CONCLUSIONS: The four sleep
      problems considered here are of public health significance because of their high
      prevalence and significant associations with role impairment.

PMID- 16952335
TI  - Brain-derived neurotrophic factor, serotonin transporter, and depression: comment
      on Kaufman et al.

PMID- 16952336
TI  - Distribution of calbindin-28kD and parvalbumin in V1 in normal adult Cebus apella
      monkeys and in monkeys with retinal lesions.
AB  - Several proteins have their normal patterns of distributions altered by monocular
      visual deprivation. We studied the distribution of the calcium-binding proteins
      calbindin-28kD (Cb) and parvalbumin (Pv) in V1 in normal adult Cebus apella
      monkeys and in monkeys with monocular retinal lesions. In normal monkeys, the
      interblobs regions in layers 2/3 and the layer 4B are intensely labeled for Cb,
      while Pv reaction showed a complementary labeling pattern with a stronger
      staining in layers 4A, 4C and in the blob regions in layers 2/3. In monkeys with
      monocular retinal lesion, the laminar distribution of these proteins was
      differentially affected, although both reactions resulted in stronger labeling in
      non-deprived ocular dominance columns. While Cb reaction resulted in stronger
      labeling in layers 1 through 5, Pv labeling was heavier in layers 2/3, 4A and 4C.
      There was a clear reduction in the intensity of neuropil staining for both Pv and
      Cb in deprived ocular dominance columns with little or no reduction in number of
      labeled cells. This reduction could thus be attributed to activity-dependent
      changes at synapses level.

PMID- 16952337
TI  - Identification and characterization of somatosensory off responses.
AB  - Event-related potentials (ERPs) have been recorded in response to the offset of
      sensory stimulation in both the auditory and visual modalities. The present
      experiment employed vibratory stimulation to characterize somatosensory ERPs in
      response to different duration stimuli. In two separate experiments, we recorded
      attended and unattended somatosensory ERPs to 70 Hz, sine wave stimuli using the
      following durations: 20 ms, 50 ms, 70 ms, 150 ms, 170 ms, 250 ms and 1000 ms. An
      oscillating coil delivered stimuli through a 'T-bar' to digits 2 and 3 of the
      right hand. The amplitude and latency measurements of P50, P100 and a later
      negative component (No1) were analyzed using MANOVA. There was no significant
      difference in the latency values of the P50 and P100, but as the duration
      increased, there was a significant increase (P < 0.01) in the latency of No1. No1
      appeared 130 ms +/- 9 ms following the offset of the stimulus. Amplitude values
      of the P50 and P100 components decreased as the stimulus duration increased and
      this effect became significant (P < 0.05) as the duration difference increased.
      Stimuli of 150 ms or greater evoked a negative baseline shift that persisted for
      the duration of the stimulus and area measurements in 7 out of the 10 subjects
      showed a significant increase in amplitude when the stimulus was attended. An
      intracranial case study supported these findings. The characteristics of the No1
      component indicate it is a somatosensory off response, and it, in conjunction
      with the P50 and sustained potential, may reflect activity of a neural system
      that is responsive to changes in the tactile environment.

PMID- 16952338
TI  - Electrophysiological differentiation of phonological and semantic integration in
      word and sentence contexts.
AB  - During auditory language comprehension, listeners need to rapidly extract meaning
      from the continuous speech-stream. It is a matter of debate when and how
      contextual information constrains the activation of lexical representations in
      meaningful contexts. Electrophysiological studies of spoken language
      comprehension have identified an event-related potential (ERP) that was sensitive
      to phonological properties of speech, which was termed the phonological mismatch
      negativity (PMN). With the PMN, early lexical processing could potentially be
      distinguished from processes of semantic integration in spoken language
      comprehension. However, the sensitivity of the PMN to phonological processing per
      se has been questioned, and it has additionally been suggested that the "PMN" is
      not separable from the N400, an ERP that is sensitive to semantic aspects of the
      input. Here, we investigated whether or not a separable PMN exists and if it
      reflects purely phonological aspects of the speech input. In the present
      experiment, ERPs were recorded from healthy young adults (N=24) while they
      listened to sentences and word lists, in which we manipulated semantic and
      phonological expectation and congruency of the final word. ERPs sensitive to
      phonological processing were elicited only when phonological expectancy was
      violated in lists of words, but not during normal sentential processing. This
      suggests a differential role of phonological processing in more or less
      meaningful contexts and indicates a very early influence of the overall context
      on lexical processing in sentences.

PMID- 16952339
TI  - Use of TTC staining for the evaluation of tissue injury in the early phases of
      reperfusion after focal cerebral ischemia in rats.
AB  - BACKGROUND AND PURPOSE: 2,3,5-Triphenyltetrazolium chloride (TTC) staining
      measures tissue viability used to evaluate infarct size. The goal of this study
      was to compare viability of neuronal tissue during the early phases of ischemia
      reperfusion assessed either by perfusion of the brain with TTC solution
      transcardially, in vivo, or by staining brain slices, in vitro. METHODS: The
      middle cerebral artery was occluded for 1 h in male SPRD rats and then reperfused
      for 0, 1, 4, 8, 16 and 24 h. Ischemic damage was evaluated by TTC staining, in
      vivo and in vitro, and by histology (Luxol Fast Blue and Fluoro-Jade staining,
      electron microscopy). RESULTS: Core volume of tissue injury measured in vivo was
      large at 0 h and steadily decreased by 50% (p<0.001) up to 16 h, but
      substantially increased from 16 to 24 h of reperfusion. In contrast, a
      significant core volume appeared at 4 h only, in vitro, and gradually increased
      up to 24 h. Core volume was larger in vivo than in vitro at all times except at
      16 h when the opposite was observed. Evans blue administered intracardially
      stained TTC-negative areas at 1 and 24 h. Histology covered the evolution of
      serious tissue injury but also demonstrated some morphologically preserved
      neurons in the infracted area at 24 h. CONCLUSIONS: Formation of formazan from
      TTC can depend on both the staining method and the metabolic burden of the brain
      tissue causing uncertainties in the volume of ischemia-induced brain injury
      measured by TTC staining.

PMID- 16952340
TI  - Cilostazol reduces ischemic brain damage partly by inducing metallothionein-1 and
      -2.
AB  - The neuroprotective effect of cilostazol, an antiplatelet drug, was examined
      after 24 h permanent middle cerebral artery (MCA) occlusion in mice, and explored
      the possible underlying mechanism by examining metallothionein (MT)-1 and -2
      induction in vivo. Cilostazol (30 mg/kg) was intraperitoneally administered at 12
      h before, 1 h before, and just after MCA occlusion. Mice were euthanized at 24 h
      after the occlusion, and the neuronal damage was evaluated using 2,3,5
      triphenyltetrazolium chloride (TTC) staining. Cilostazol significantly reduced
      the infarct area and volume, especially in the cortex. Real-time RT-PCR revealed
      increased mRNA expressions for MT-1 and -2 in the cortex of normal brains at 6 h
      after cilostazol treatment without MCA occlusion. MT-1 and -2 immunoreactivity
      was also increased in the cortex of such mice, and this immunoreactivity was
      observed in the ischemic hemisphere at 24 h after MCA occlusion (without
      cilostazol treatment). The strongest MT-1 and -2 immunoreactivity was detected in
      MCA-occlused mice treated with cilostazol [in the peri-infarct zone of the cortex
      (penumbral zone)]. These findings indicate that cilostazol has neuroprotective
      effects in vivo against permanent focal cerebral ischemia, especially in the
      penumbral zone in the cortex, and that MT-1 and -2 may be partly responsible for
      these neuroprotective effects.

PMID- 16952341
TI  - Age-related changes in cell density and the proliferation rate of olfactory
      ensheathing cells in the lamina propria of postnatal mouse olfactory mucosa.
AB  - We investigated age-related changes in the distribution and proliferation of
      olfactory ensheathing cells (OECs) in postnatal mouse olfactory mucosa. In
      contrast to reported data on other glial cell types in the peripheral and central
      nervous systems, OEC cell density in the olfactory nerve bundles in the lamina
      propria remained almost constant from 10 days through 16 months of age. Electron
      microscopy of the nerve bundles revealed that axon packing density also was
      constant during that period. These findings suggest that the ratio of the number
      of OECs to the unit length of the olfactory neuron axons ensheathed by them does
      not change markedly throughout the lifetime of mice in an undisturbed condition.
      By contrast, OEC proliferative density decreased rapidly in the 10-day to 1-month
      old period, showing a significant difference, and for the rest of life remained
      at low level, similar to previous values reported for other glial cell types.

PMID- 16952342
TI  - Synthesis of beta-(1-->6)-linked glucosamine oligosaccharides corresponding to
      fragments of the bacterial surface polysaccharide poly-N-acetylglucosamine.
AB  - A series of 3-beta-acetamidopropyl oligo-beta-(1-->6)-glucosamines consisting of
      5, 7, 9 and 11 glucosamine residues, and a series of corresponding per-N
      acetylated derivatives were synthesized using a convergent blockwise approach.
      These compounds represent fragments of a bacterial surface polysaccharide
      produced by numerous bacterial pathogens, including Staphylococcus aureus, and
      will be used as models for its biochemical and immunological properties.

PMID- 16952343
TI  - Formation of lactic acid from glycolaldehyde by alkaline hydrothermal reaction.
AB  - Alkali hydrothermal experiments with glycolaldehyde were carried out at 300
      degrees C. Glycolaldehyde was converted into lactic acid in a yield of 28% based
      on the starting carbon mass of glycolaldehyde. A conversion pathway for
      glycolaldehyde into lactic acid is proposed and our results suggest that the
      pathway via glycolaldehyde is also important in the conversion of glucose into
      lactic acid.

PMID- 16952344
TI  - MM3 potential energy surfaces of trisaccharide models of lambda-, mu-, and nu
      carrageenans.
AB  - The adiabatic potential energy surfaces (PES) of six trisaccharides, sulfated
      derivatives of alpha-D-Gal p-(1-->3)-beta-D-Gal p-(1-->4)-alpha-D-Gal p and beta
      D-Gal p-(1-->4)-alpha-D-Gal p-(1-->3)-beta-D-Gal p representing models of lambda
      , mu-, and nu-carrageenans were obtained using the MM3 force-field at epsilon =
      3. Each PES was described by a single contour map for which the energy is plotted
      against the two psi glycosidic angles, given the small variations of the phi
      glycosidic torsional angle in the low-energy regions of disaccharide maps. Most
      surfaces appear as expected from the maps of the disaccharidic repeating units of
      carrageenans, with less important factors altering the additive effect of both
      linkages. Only small interactions between the first and third monosaccharidic
      moieties of the trisaccharides are observed. The flexibility of the alpha
      linkages appears nearly identical to that in their disaccharide counterparts,
      with only one exception, where it appears reduced by the presence of the third
      monosaccharide. On the other hand, the flexibility of the beta-linkage appears to
      be equal or sometimes even higher than that observed for the corresponding
      disaccharide.

PMID- 16952345
TI  - Efficient screening method of the thiopurine methyltransferase polymorphisms for
      patients considering taking thiopurine drugs in a Chinese Han population in Henan
      Province (central China).
AB  - BACKGROUND: Thiopurine S-methyltransferase (TPMT) is an enzyme that catalyzed the
      S-methylation of thiopurine drugs. TPMT activity exhibits an interindividual
      variability, mainly as a result of genetic polymorphism. Patients with
      intermediate or deficient TPMT activity are at risk for toxicity after receiving
      standard doses of thiopurine drugs. We determined a cut-off concentration of the
      TPMT activity assay less than which genotyping of the TPMT gene should be
      performed. In addition, the influence of hemodialysis on TPMT activity in uremic
      patients was examined. METHODS: In 248 healthy subjects and 30 uremic patients,
      PCR-based methods were used to analyze the most common functional mutations
      TPMT2, 3A, 3B and 3C. A HPLC assay was used to measure erythrocyte TPMT activity
      in the whole population. RESULTS: Seven TPMT3C heterozygotes were identified,
      while TPMT2, 3A and 3B alleles were not detected in 248 healthy subjects. The
      frequency of TPMT3C allele was 1.4% (7/496). The TPMT activity in healthy
      subjects was normally distributed, ranged from 6.09 to 28.65 nmol/h/ml pRBC with
      a mean of 16.03 +/- 4.16 nmol/h/ml pRBC. The cut-off for high TPMT activity and
      intermediate TPMT activity was 10.07 nmol/h/ml pRBC. There were 19 intermediate
      activity healthy subjects (7.7%) and 229 high activity healthy subjects (92.3%),
      and no TPMT deficiency subject was found. All of the 229 healthy subjects with
      high activity had no mutant alleles, while 7 of the 19 subjects with intermediate
      activity had a mutant allele. Phenotypes were in good agreement with genotypes
      for 95% of subjects. The uremic patients were all homozygous for the wild-type
      allele whose TPMT activity was activated significantly before hemodialysis
      compared with TPMT activity after hemodialysis. CONCLUSIONS: We defined the cut
      off values for the TPMT phenotyping assay at 10.07 nmol/h/ml pRBC, less than
      which additional genotyping elucidates the individual risk for drug therapy. In
      uremic patients, TPMT activity is increased by some uremic factors, and dialysis
      shifted their TPMT activity close to that of a healthy control group.

PMID- 16952346
TI  - Components of both major axial patterning systems of the Bilateria are
      differentially expressed along the primary axis of a 'radiate' animal, the
      anthozoan cnidarian Acropora millepora.
AB  - Cnidarians are animals with a single (oral/aboral) overt body axis and with
      origins that nominally predate bilaterality. To better understand the evolution
      of axial patterning mechanisms, we characterized genes from the coral, Acropora
      millepora (Class Anthozoa) that are considered to be unambiguous markers of the
      bilaterian anterior/posterior and dorsal/ventral axes. Homologs of Otx/otd and
      Emx/ems, definitive anterior markers across the Bilateria, are expressed at
      opposite ends of the Acropora larva; otxA-Am initially around the blastopore and
      later preferentially toward the oral end in the ectoderm, and emx-Am
      predominantly in putative neurons in the aboral half of the planula larva, in a
      domain overlapping that of cnox-2Am, a Gsh/ind gene. The Acropora homologs of Pax
      3/7, NKX2.1/vnd and Msx/msh are expressed in axially restricted and largely non
      overlapping patterns in larval ectoderm. In Acropora, components of both the D/V
      and A/P patterning systems of bilateral animals are therefore expressed in
      regionally restricted patterns along the single overt body axis of the planula
      larva, and two 'anterior' markers are expressed at opposite ends of the axis.
      Thus, although some specific gene functions appear to be conserved between
      cnidarians and higher animals, no simple relationship exists between axial
      patterning systems in the two groups.

PMID- 16952348
TI  - 'Maternal hair--an appropriate matrix for detecting maternal exposure to
      pesticides during pregnancy', by Ostrea et al.

PMID- 16952347
TI  - BMP signaling regulates murine enteric nervous system precursor migration,
      neurite fasciculation, and patterning via altered Ncam1 polysialic acid addition.
AB  - The enteric nervous system (ENS) forms from migrating neural crest-derived
      precursors that differentiate into neurons and glia, aggregate into ganglion cell
      clusters, and extend neuronal processes to form a complex interacting network
      that controls many aspects of intestinal function. Bone morphogenetic proteins
      (BMPs) have diverse roles in development and influence the differentiation,
      proliferation, and survival of ENS precursors. We hypothesized that BMP signaling
      might also be important for the ENS precursor migration, ganglion cell
      aggregation, and neurite fasciculation necessary to form the enteric nervous
      system. We now demonstrate that BMP signaling restricts murine ENS precursors to
      the outer bowel wall during migration. In addition, blocking BMP signaling causes
      faster colonization of the murine colon, reduces ganglion cell aggregation, and
      reduces neurite fasciculation. BMP signaling also influences patterns of neurite
      extension within the developing bowel wall. These effects on ENS precursor
      migration and neurite fasciculation appear to be mediated at least in part by
      increased polysialic acid addition to neural cell adhesion molecule (Ncam1) in
      response to BMP. Removing PSA enzymatically reverses the BMP effects on ENS
      precursor migration and neurite fasciculation. These studies demonstrate several
      novel roles for BMP signaling and highlight new functions for sialyltransferases
      in the developing ENS.

PMID- 16952349
TI  - Cognitive dysfunction induced by sequential injection of amyloid-beta and
      ibotenate into the bilateral hippocampus; protection by memantine and MK-801.
AB  - Aggregated 40-residue amyloid-beta peptide (beta40, 4 microg/microl), and 2 days
      later, ibotenate (NMDA receptor agonist, 0.3 microg/0.5 microl), were bilaterally
      injected into the hippocampus of rats. Five to six weeks after the beta40
      injection, the rats showed learning deficits in the Morris water maze task and
      neuronal damage in the hippocampus, although the injection of beta40 or ibotenate
      alone did not result in cognitive deficits and hippocampal damage. Memantine (10,
      20 mg/kg/day s.c. infusion for 6 weeks starting 24 h before the beta40 injection)
      significantly prevented learning deficits as measured for 4 days from 5 weeks
      after the beta40 injection, while a lower dose of memantine (5 mg/kg/day) and MK
      801 (0.312, 0.624 mg/kg/day) did not have inhibitory effects on the learning
      deficits. The neuronal damage in the hippocampus, assessed as an elevation of the
      levels of the peripheral-type benzodiazepine-binding site (a gliosis marker for
      neuronal damage) produced by sequential intra-hippocampal injections of beta40
      and ibotenate, at 6 weeks (39 days) after the beta40 injection, was significantly
      attenuated by memantine (10, 20 mg/kg/day) and MK-801 (0.624 mg/kg/day). These
      protective effects were also confirmed by histochemical examination (Cresyl
      violet staining of brain slices). In naive rats, MK-801 produced a significant
      learning impairment in the water maze task at a dose of 0.624 mg/kg/day, while
      memantine (20 mg/kg/day s.c. infusion) did not, although the beta40 plus
      ibotenate-induced hippocampal damage was lessened by both treatments. These
      results suggest that memantine and MK-801 exert protective effects on progressive
      neuronal damage, but that only memantine prevents memory impairment in
      hippocampal-lesioned rats, and that memantine may be a beneficial agent for the
      treatment of progressive cognitive dysfunction including Alzheimer's disease-type
      dementia.

PMID- 16952350
TI  - Influence of pharmacologically-induced experimental anxiety on nociception and
      antinociception in rats.
AB  - Animal studies reveal that diverse environmental stimuli that generate anxiety
      like behaviors also induce antinociception; conversely, clinical data show that
      pain perception is reduced under anxiolysis. This study was conducted to
      investigate the influence of pharmacologically induced-anxiety on nociception and
      antinociception. Experimental anxiety levels were measured using the rat burying
      behavior test. Diazepam (0, 0.5, 1.0 and 2.0 mg/kg, i.p.) or yohimbine (0, 0.5
      and 1.0 mg/kg, i.p.) were used as anxiolytic or anxiogenic drugs, respectively.
      To evaluate the influence of different experimental anxiety levels on
      nociception, the pain-induced functional impairment in the rat (PIFIR model) was
      used. Nociception was induced by an intra-articular injection of 15% uric acid
      into the knee joint of the right hind limb. Diazepam or yohimbine were
      administered 15 min before uric acid and the ability of the rat to use the
      injured hind limb was recorded. To analyze the influence of different levels of
      anxiety on the antinociceptive effects produced by acetylsalicylic acid (0, 31,
      100 and 310 mg/kg, p.o.); this analgesic was administered 3.5 h after uric acid.
      Fifteen min before diazepam (2.0 mg/kg) or yohimbine (1.0 mg/kg) were
      administered. We found that, in the burying behavior test, diazepam and yohimbine
      produced a dose-dependent decrease or augment in the cumulative time of burying,
      effects denoting reduced or increased experimental anxiety, respectively.
      Diazepam or yohimbine, administered alone, was unable to produce nociception. The
      results showed an influence of anxiety on nociception since a decreased (by
      diazepam) or increased (by yohimbine) experimental anxiety prevented nociception.
      Control experiments showed that acetylsalicylic acid did not modify experimental
      anxiety in the burying behavior test, but effectively reversed the nociception
      induced by uric acid (15%) in the PIFIR model. Such antinociceptive effect was
      unmodified by the anxiolytic or anxiogenic actions of diazepam or yohimbine. Data
      are discussed on the bases of clinical- and animal-studies revealing interactions
      between anxiety and nociception.

PMID- 16952351
TI  - Inhibition of nuclear factor kappaB is associated with neuroprotective effects of
      glycyrrhizic acid on glutamate-induced excitotoxicity in primary neurons.
AB  - Glycyrrhizic acid is an herbal drug with a broad spectrum of antiviral activities
      and pharmacological effects and multiple sites of action. We investigated whether
      glycyrrhizic acid protects against glutamate-induced excitotoxicity and the
      underlying mechanisms. We found that glycyrrhizic acid protected against
      neurotoxicity in rat primary neuronal cultures and hippocampal slices by
      suppression of the glutamate-induced apoptosis. Glycyrrhizic acid conferred
      neuroprotective properties in a concentration-dependent manner, as determined by
      cell survival, apoptosis, and Ca(2+) influx. Glycyrrhizic acid selectively
      inhibited the Ca(2+) influx activated through N-methyl-D-aspartate (NMDA)
      receptor by glutamate, but not through membrane depolarization elicited by high
      K(+) induction. Glycyrrhizic acid treatment also diminished glutamate-induced DNA
      fragmentation and cleavage of poly (ADP-ribose) polymerase (PARP).
      Electrophoretic mobility shift assay (EMSA) indicated that glycyrrhizic acid
      inhibited the binding activity of nuclear factor kappaB (NF-kappaB) to its target
      elements. Western blot analysis of NF-kappaB inhibitor (IkappaBalpha) protein
      revealed that the inhibitory effect of glycyrrhizic acid on glutamate-induced
      activation of NF-kappaB activity was attributable to the inhibition of IkappaB
      kinase activity. Thus, the site of action of glycyrrhizic acid could be a
      downstream consequence of Ca(2+)entry through NMDA receptors and that NF-kappaB
      may be one downstream target in this process. These observations suggest that
      glycyrrhizic acid may be of therapeutic value for the prevention of cerebral
      damage elicited by the glutamate.

PMID- 16952352
TI  - Tyrosine residues 654 and 670 in beta-catenin are crucial in regulation of Met
      beta-catenin interactions.
AB  - beta-Catenin, a key component of the canonical Wnt pathway, is also regulated by
      tyrosine phosphorylation that regulates its association to E-cadherin.
      Previously, we reported its association with the hepatocyte growth factor (HGF)
      receptor Met at the membrane. HGF induced Met-beta-catenin dissociation and
      nuclear translocation of beta-catenin, which was tyrosine-phosphorylation
      dependent. Here, we further investigate the Met-beta-catenin interaction by
      selectively mutating several tyrosine residues, alone or in combination, in beta
      catenin. The mutants were subcloned into FLAG-CMV vector and stably transfected
      into rat hepatoma cells, which were treated with HGF. All single or double-mutant
      transfected cells continued to show HGF-induced nuclear translocation of FLAG
      beta-catenin except the mutations affecting 654 and 670 simultaneously
      (Y654/670F), which coincided with the lack of formation of beta-catenin-TCF
      complex and DNA synthesis, in response to the HGF treatment. In addition, the
      Y654/670F-transfected cells also showed no phosphorylation of beta-catenin or
      dissociation from Met in response to HGF. Thus, intact 654 and 670 tyrosine
      residues in beta-catenin are crucial in HGF-mediated beta-catenin translocation,
      activation and mitogenesis.

PMID- 16952353
TI  - Zinc finger transcription factor Slug is a novel target gene of aryl hydrocarbon
      receptor.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor.
      We previously showed that AhR localizes predominantly in the cytoplasm under high
      cell densities of a keratinocytes cell line, HaCaT, but accumulates in the
      nucleus at low cell densities. In the current report, we show that the Slug,
      which is a member of the snail/slug family of zinc finger transcriptional
      repressors critical for induction of epithelial-mesenchymal transitions (EMT), is
      activated transcriptionally in accordance with nuclear accumulation of AhR. By
      reporter assay of the promoter of the Slug gene, gel shift and chromatin
      immunoprecipitation analyses showed AhR directly binds to xenobiotic responsive
      element 5 at -0.7 kb of the gene. AhR-targeted gene silencing by small
      interfering RNA duplexes led to the abolishment of not only CYP1A1 but also Slug
      induction by 3-methycholanthrene. The Slug was co-localized to the AhR at the
      wound margins of HaCaT cells, where apparent nuclear distribution of AhR and Slug
      was observed. The induced Slug was associated with reduction of an epithelial
      marker of cytokeratin-18 and with an increase in the mesenchymal marker,
      fibronectin. Taken together, these findings suggest that AhR participated in Slug
      induction, which, in turn, regulates cellular physiology including cell adhesion
      and migration.

PMID- 16952354
TI  - Promotion of haematopoietic activity in embryonic stem cells by the aorta-gonad
      mesonephros microenvironment.
AB  - We investigated whether the in vitro differentiation of ES cells into
      haematopoietic progenitors could be enhanced by exposure to the aorta-gonadal
      mesonephros (AGM) microenvironment that is involved in the generation of
      haematopoietic stem cells (HSC) during embryonic development. We established a co
      culture system that combines the requirements for primary organ culture and
      differentiating ES cells and showed that exposure of differentiating ES cells to
      the primary AGM region results in a significant increase in the number of ES
      derived haematopoietic progenitors. Co-culture of ES cells on the AM20-1B4
      stromal cell line derived from the AGM region also increases haematopoietic
      activity. We conclude that factors promoting the haematopoietic activity of
      differentiating ES cells present in primary AGM explants are partially retained
      in the AM20.1B4 stromal cell line and that these factors are likely to be
      different to those required for adult HSC maintenance.

PMID- 16952355
TI  - The prion protein is neuroprotective against retinal degeneration in vivo.
AB  - A common feature of neurodegenerative disorders is acute or progressive loss of
      neurons due to apoptosis. The pathological isoform of the prion protein is
      associated with retinal apoptosis and the cellular isoform (PrPc) has been shown
      to mediate protection from apoptosis in cell culture and in neonatal retinal
      explants. Using a model of light-induced photoreceptor apoptosis, we show in vivo
      that the levels of PrPc expression in the retina inversely correlate with the
      susceptibility of photoreceptors to light damage. Dissection of apoptotic
      signalling cascades suggests that PrPc acts neuroprotectively downstream of AP-1
      induction. Our results reveal PrP as a neuroprotective/anti-apoptotic factor in
      vivo and suggest that PrPc may function as a guardian of neuronal integrity.

PMID- 16952356
TI  - A critical role of CREB in the impairment of late-phase LTP by adult onset
      hypothyroidism.
AB  - We have shown previously that adult onset hypothyroidism impairs late-phase long
      term potentiation (L-LTP) and reduces the protein levels of mitogen-activated
      protein kinases (MAPKp44/42 (ERK1/2)) in area CA1 of the hippocampus. In the
      present study, basal and stimulated levels of signaling molecules essential for
      the expression of L-LTP were determined in area CA1 of the hippocampus. L-LTP was
      evoked by multiple train high-frequency stimulation (MHFS) in area CA1 of the
      hippocampus of thyroidectomized and sham control anesthetized adult rats.
      Immunoblot analysis showed reduction in the basal protein levels of adenylyl
      cyclase I (ACI), calcium calmodulin-dependent protein kinase IV (CaMKIV), and
      cyclic-AMP response element-binding protein (CREB; phosphorylated (P-) and total)
      in hypothyroid rats. A significant increase in the levels of P-CREB, P-MAPKp44
      and P-MAPKp42 was seen 4 h after MHFS in sham-operated control animals, but not
      in hypothyroid animals. The levels of total CREB, total MAPKp44, total MAPKp42
      and CaMKIV were elevated in both groups 4 h after MHFS. Our results suggest that
      in adult hypothyroid rats, the reduced basal level of CaMKIV, MAPKp44/42 and CREB
      along with the failure of MHFS to induce MAPKp44/42 and CREB phosphorylation may
      be responsible for L-LTP impairment in the CA1 area during hypothyroidism.

PMID- 16952357
TI  - Destruction of primordial ovarian follicles in adult cynomolgus macaques after
      exposure to 4-vinylcyclohexene diepoxide: a nonhuman primate model of the
      menopausal transition.
AB  - OBJECTIVE: To determine whether the 4-vinylcyclohexene diepoxide (VCD)-treated
      mouse menopause model, which involves accelerated atresia of primordial follicles
      and induces gradual ovarian failure (while sparing the ovarian stroma), can be
      adapted to nonhuman primates. DESIGN: Controlled periclinical trial (nonhuman
      primates). SETTING: Comparative Medicine Clinical Research Center. ANIMAL(S):
      Four adult female cynomolgus monkeys. INTERVENTION(S): Once-daily i.m. injections
      for 15 days as follows: vehicle or VCD doses of 80 mg/kg, 160 mg/kg, 250 mg/kg.
      Ovaries were removed 27 days after treatment, and pathological determinations
      were made at necropsy. MAIN OUTCOME MEASURE(S): Baseline and interim hematologic
      and biochemical measures, physical exams, and body weights. Follicle counts and
      organ evaluation at necropsy. RESULT(S): A nearly complete elimination of
      primordial, intermediate, primary and secondary follicles was achieved with 250
      mg/kg VCD. A 50% reduction in primordial and primary follicles was observed with
      160 mg/kg VCD. No effect of 80 mg/kg VCD per day was observed. Clinical health
      measures remained within normal range except for transient, mild increases in
      liver enzymes and an inflammatory response at the injection site with 250 mg/kg.
      Postmortem evaluations (9 months) revealed no gross or histological lesions in
      the organs studied. CONCLUSION(S): These results demonstrate that the monkey
      ovary is susceptible to VCD and that as in rodents, primordial and primary
      follicles are targeted selectively.

PMID- 16952358
TI  - An in vivo murine model of rosiglitazone use in pregnancy.
AB  - OBJECTIVE: To identify the effects of rosiglitazone use during murine pregnancy.
      DESIGN: The effect of rosiglitazone on blastocyst development was determined by
      culturing two-cell mouse embryos with rosiglitazone for 72 hours. From January to
      June 2005, five independent groups of ICR/CD1 female mice were treated with
      rosiglitazone during pregnancy, from the time of identification of seminal plugs
      until delivery of pups. SETTING: Controlled animal facility. ANIMAL(S): Two-cell
      mouse embryos and an outbred line of mice, ICR/CD1. INTERVENTION(S): Two-cell
      embryos were cocultured with rosiglitazone (10 microM) for 72 hours and scored.
      Ten-week-old female ICR mice were mated. Females with seminal plugs then were
      randomized to rosiglitazone (10 or 0.1 mg/kg per day) or to carrier alone, by
      gavage, until delivery. Weekly weights were obtained, and pregnancy outcomes were
      documented. MAIN OUTCOME MEASURE(S): Blastocyst development, number of pups and
      pup weights, and morphological changes. RESULT(S): Embryos exposed to
      rosiglitazone progressed to the blastocyst stage within 72 hours. Pregnant
      animals demonstrated normal weight gain throughout pregnancy. Postnatal growth
      and litter size were not statistically different between groups. No changes in
      normal mouse neonate development were observed. CONCLUSION(S): Rosiglitazone did
      not impair murine blastocyst development in vitro or cause phenotypic harm to the
      mouse fetus when administered during pregnancy, suggesting potential safety for
      rosiglitazone use in pregnancy.

PMID- 16952359
TI  - Long-term suppression of reproductive function by a single dose of gonadotropin
      releasing hormone antagonists in a sheep model.
AB  - OBJECTIVE: To determine the effect of single long-acting doses of GnRH
      antagonists on reproductive function in a sheep model. DESIGN: Observational,
      model study. SETTING: University-affiliated research unit. ANIMAL(S): Nine intact
      mature Merino sheep in experiment 1 and 12 mature Merino-crossed ewes with the
      ovary autotransplanted to the neck in experiment 2. INTERVENTION(S):
      Synchronization of estrous cycle either with intravaginal progestins or
      prostaglandin F2alpha analogues and treatment with a single dose of GnRH
      antagonist; evaluation of reproductive activity, plasma sampling, and ovarian
      ultrasonography. MAIN OUTCOME MEASURE(S): Determination of estrus behavior;
      plasma concentrations of P, FSH, LH, and inhibin A; and number and size of
      ovarian follicles. RESULT(S): In both experiments, the concentrations of FSH and
      LH were suppressed when compared with those in control ewes. In experiment 1, the
      ovulatory cycles were suppressed for > or = 55 days in treated sheep. In
      experiment 2, there were no follicles sized > or = 5 mm in treated ewes for 50
      days. CONCLUSION(S): The suppression of the development of large follicles for >
      or = 30 days after a single injection of a long-acting GnRH antagonist provides a
      novel convenient method of pretreatment before COS.

PMID- 16952360
TI  - Serum replacement with a growth factor-free synthetic substance in culture medium
      contributes to effective establishment of mouse embryonic stem cells of various
      origins.
AB  - OBJECTIVE: To evaluate whether serum replacement with growth factor-free
      synthetic substances contributed to the effective establishment of embryonic stem
      (ES) cells. DESIGN: Randomized, prospective model study. SETTING: Gamete and stem
      cell biotechnology laboratory at Seoul National University in Korea. ANIMAL(S):
      F1 (C57BL6 x DBA2) mice. INTERVENTION(S): Blastocysts of different origins were
      cultured in serum-replaced media. MAIN OUTCOME MEASURE(S): Embryonic stem cell
      establishment. RESULT(S): Eight batches of ES cells were established from colony
      forming inner cell mass cells after the replacement of fetal bovine serum (FBS)
      with synthetic knockout serum replacement (KSR) in mkDMEM. The established cells
      were positive for ES cell markers and formed both embryoid bodies in vitro and
      teratomas in vivo, but the established cell batches and control (transformed) ES
      cells responded differently to the culture media. Higher levels of cell viability
      were detected after the replacement with the 75:25 FBS-KSR mixture than with any
      other mixtures, and a gradual decrease in viability was detected as the KSR
      volume ratio was increased. The 75:25 FBS-KSR mixture-containing medium supported
      ES cell establishment of outbred ICR, F1, and F2 of C57BL6/DBA2; F1
      parthenogenetic and ES cell-complemented tetraploid blastocysts; and single ES
      cell cultures. CONCLUSION(S): A serum-replaced medium could be used for effective
      ES-cell establishment of various origins.

PMID- 16952361
TI  - Exogenous testosterone reverses age-related atrophy in a spinal neuromuscular
      system.
AB  - Aging is associated with a variety of pathologies, including motor dysfunctions
      and reductions in sexual behavior. In male rats, declines in sexual behavior
      during the aging process may be caused in part by the loss of the lumbar spinal
      cord motoneurons that innervate the penile musculature. Alternatively, declining
      sexual behavior may be caused by the precipitous reductions in circulating
      testosterone that occur during aging. In this paper, we report two experiments
      examining these issues. In Experiment 1, we counted motoneurons in the lumbar
      motor nuclei and measured several androgen-sensitive morphological properties of
      the penile muscles and their innervating motoneurons at several time points
      during the aging process. Motoneuron number in the lumbar nuclei did not change
      over time, even with very advanced age. In contrast, the penile muscles and their
      innervating motoneurons underwent profound atrophy, with muscle weight and
      motoneuron dendritic length declining to less than 50% of young adult levels. In
      Experiment 2, we treated aged animals with exogenous testosterone, and then
      examined their penile neuromuscular systems for morphological changes.
      Testosterone treatment, both acute and chronic, completely reversed age-related
      declines in the weight of the penile muscles and in the soma size and dendritic
      length of their innervating motoneurons. Together, these data suggest that
      reductions in male sexual behavior during the aging process are caused primarily
      by declines in testosterone levels rather than motoneuron loss. Furthermore, they
      raise the possibility that testosterone treatment could play an important role in
      maintaining neuronal connectivity in the aging body.

PMID- 16952362
TI  - Recombinant human bone morphogenetic protein-7 for treatment of long bone non
      union: an observational, retrospective, non-randomized study of 105 patients.
AB  - Autogenous bone-grafting is frequently used in the treatment of fracture non
      union. The donor-site morbidity and potentially limited supply of suitable
      autogenous bone are commonly recognized drawbacks. Recent studies advocated the
      benefit and safety of recombinant human bone morphogenetic protein-7 (rhBMP-7) in
      several anatomical sites. An observational, retrospective, non-randomized study
      on the use of BMP-7 in treating non-union in various sites has been carried out
      by the BMP-7 Italian Observational Study (BIOS) Group. The clinical series
      included 105 patients. Additional grafts were used based on the surgeon's
      decision. Radiographic and clinical assessments were carried out at progressive
      time intervals on two groups: BMP-7+autograft (A) or BMP-7 (B). The mean follow
      up was 29.2 months. The last assessment showed an 88.8% success rate with an
      average healing time of 7.9 months. At >/=9 months there was overlapping between
      the unions recorded in the two groups (PA-PB=1.5%; CI 95%: -0.149; 0.119). This
      is an observational study that illustrates the efficacy of BMP-7 with and without
      bone grafting for the treatment of long bone non-unions.

PMID- 16952363
TI  - Symptom experience, psychological distress, and quality of life in Korean
      patients with liver cirrhosis: a cross-sectional survey.
AB  - BACKGROUND: In patients with cirrhosis, quality of life (QOL) is seriously
      impaired and associated with particular symptoms such as fatigue, muscle cramps
      or pruritus. However, there is lack of evidence about the overall symptom
      experience in patients with cirrhosis, in addition, most studies on QOL have
      focused only on identifying the relationship between disease-related variables
      such as disease severity, etiology or serological markers and QOL. OBJECTIVES:
      This study aimed to describe symptom experience, psychological distress, and QOL
      in Korean patients with liver cirrhosis, and to identify the factors that predict
      their quality of life. DESIGN: This study is a cross-sectional, descriptive
      design. SETTINGS: The participants were recruited over a 2-month period,
      September 27 to November 25, 2003 from the outpatient or inpatient departments of
      gastroenterology at two large university hospitals in Seoul, Korea. PARTICIPANTS:
      There were 129 patients, mean age was 53.6 years, who met eligibility criteria
      and agreed to participate in the study. METHODS: Symptom experience was measured
      with a scale developed by the researchers through a literature review on liver
      cirrhosis. Psychological distress was measured with the anxiety/depression
      category from the modified Korean version of the profile of mood states (POMS)
      [Shin, 1996. A study on verification of the profile of mood states (POMS) for
      Korean elders. Journal of Korean Academic Nursing 26, 743-758], and QOL was
      measured with quality of life index (QLI) developed by Ferrans and Powers [1985,
      Quality of life index: development and psychometric properties. Advances in
      Nursing Science 8, 15-24. ]. RESULTS: The results indicated that (1) overall
      symptom experience score was relatively low, major symptoms needing a management
      were fatigue, ascites and/or edema, and muscle cramps; (2) the mean score of
      psychological distress revealed mild to moderate levels of anxiety and
      depression; (3) quality of life was found to be seriously impaired; (4)
      psychological distress, employment status, and symptom experience were
      significant predictors of QOL, and explained 29.8% of the total variance.
      CONCLUSION: These results indicate that symptom management, which includes
      attention to associated psychological intervention, is imperative for improvement
      in the QOL in Korean patients with liver cirrhosis.

PMID- 16952364
TI  - Analysis of baicalein, baicalin and wogonin in Scutellariae radix and its
      preparation by microemulsion electrokinetic chromatography with 1-butyl-3
      methylimizolium tetrafluoborate ionic liquid as additive.
AB  - Microemulsion electrokinetic chromatography (MEEKC) using 1-butyl-3
      methylimidazolium tetrafluoroborate (BMIM-BF4) ionic liquid (IL) as additive was
      developed for the analysis of baicalin, wogonin and baicalein in Scutellariae
      radix and its preparation. After conducting a series of optimizations, baseline
      separation was obtained for the analytes within 5min under the optimum conditions
      (sodium dodecyl sulfate (SDS) 0.88% (m/v) ethyl acetate 0.8% (v/v) butan-1-ol
      0.2% (v/v) and the buffer composition were 25% acetonitrile (v/v), 7.5 mM BMIM
      BF4 and 10 mM NaH2PO4, pH 8.2, applied voltage 17.5 kV and detection at 254 nm),
      the method has been successfully applied to the determination and quantification
      of the analytes in the extracts of S. radix (cooked), S. radix (raw) and
      Qingfeiyihuowan which was the preparation including S. radix.

PMID- 16952365
TI  - Direct analysis of artemisinin from Artemisia annua L. using high-performance
      liquid chromatography with evaporative light scattering detector, and gas
      chromatography with flame ionization detector.
AB  - Since the isolation of artemisinin 32 years ago, it has been analyzed by
      different chromatographic techniques. This work compared the analysis of
      artemisinin from crude plant samples by GC with flame ionization detection (GC
      FID) and HPLC with evaporative light scattering detector (HPLC-ELSD). Data is
      also presented indicating that GC is suitable for the quantification of two of
      artemisinin precursors (arteannuin B and artemisinic acid) if a mass spectrometer
      is available. GC-FID and HPLC-ELSD were chosen because of their low cost compared
      to other detection methods, their ease of operation compared to HPLC with
      electrochemical detection, and because neither require artemisinin
      derivatization. Both GC-FID and HPLC-ELSD provided sensitive (ng level) and
      reproducible results for the analysis of artemisinin from field plants, with a
      correlation coefficient of r(2)=0.86 between the two methods. Both methods could
      be easily adapted to the analysis of pharmaceutical-grade artemisinin.

PMID- 16952366
TI  - Development and single-laboratory validation of a new gas chromatographic multi
      pesticide method of analysis of commercial emulsifiable concentrate formulations
      containing alachlor, chlorpyrifos methyl, fenthion and trifluralin as active
      ingredients.
AB  - A multi-pesticide (MP) method was developed and single-laboratory validated for
      the quality control of commercial pesticide products containing alachlor,
      chlorpyrifos methyl, fenthion and trifluralin as active ingredients (a.i.). A
      capillary gas chromatographic system with flame ionization detection (FID) and a
      programmable temperature vaporising split injector was used. The performance
      characteristics (specificity, linearity, precision and repeatability) of the
      method satisfied international acceptability criteria.

PMID- 16952367
TI  - COX-1 and COX-2 expression in feline oral squamous cell carcinoma.
AB  - This study demonstrated immunohistochemically the expression of cyclooxygenase-1
      (COX-1) and cyclooxygenase-2 (COX-2) in feline oral squamous cell carcinoma
      (FOSCC), with primary polyclonal antibodies raised against human epitopes. COX-2
      immunolabelling was intracytoplasmic and, in some neoplastic cells, perinuclear;
      it was demonstrated in a small proportion (< or = 1%) of neoplastic cells and its
      intensity was usually mild to moderate. In contrast, all neoplastic tissues
      showed extensive nuclear and cytoplasmic COX-1 immunolabelling. Cytoplasmic COX-1
      immunolabelling was less intense than nuclear labelling in neoplastic tissue. In
      the adjacent histologically normal oral mucosa, COX-2 immunolabelling was absent.
      The cytoplasmic and nuclear intensity and distribution of COX-1 immunolabelling
      was significantly higher in neoplastic tissue than in adjacent normal oral
      mucosa. The results indicate that COX-1 and COX-2 are overexpressed in FOSCC, but
      the clinical and pathophysiological significance of this finding remains to be
      determined.

PMID- 16952368
TI  - Choroid plexus papilloma in a Scottish highland cow.
AB  - Choroid plexus papilloma, a rare tumour in bovids, arising from the roof of the
      third ventricle was diagnosed at necropsy in a 4-year-old Scottish Highland cow.
      The animal presented with a 2-month history of progressive ataxia, ventromedial
      strabismus, and hyperaesthesia. Neoplastic epithelial cells were positive
      immunohistochemically for pancytokeratin and S-100, and negative for GFAP.
      Ultrastructurally, epithelial cells were characterized by intercellular
      junctions, zonulae adherens, and zonulae occludens. Neither cilia nor basal
      bodies were identified. The gross, microscopical, immunohistochemical and
      ultrastructural findings were consistent with those of a choroid plexus
      papilloma.

PMID- 16952369
TI  - Persistent left cranial vena cava causing oesophageal obstruction and consequent
      megaoesophagus in a dog.
AB  - A 2-month-old Brittany spaniel dog was presented for persistent regurgitation,
      first observed soon after weaning. Clinical examination and diagnostic imaging
      suggested megaoesophagus associated with a vascular ring anomaly. The normal
      location of the trachea on the X-ray was not consistent with a persistent right
      aortic arch. Post-mortem examination revealed a persistent left cranial vena cava
      that formed a non-elastic fibrous band enclosing the oesophagus and trachea, and
      causing constriction of the oesophagus. This uncommon congenital vascular defect
      has never previously been associated with megaoesophagus in the dog.

PMID- 16952370
TI  - Pathogenesis of experimental encephalomyocarditis: a histopathological,
      immunohistochemical and virological study in mice.
AB  - Mice (n=20) aged 8 weeks were infected, either by oronasal inoculation or by
      contact, with one of two different myocardial strains of encephalomyocarditis
      virus (EMCV), namely, the Greek strain 424/90 and the Belgian strain B279/95. The
      animals were killed at 18-59 days post-infection (dpi), except for two mice that
      died at 6 and 32 dpi, and samples of brain, heart, pancreas, kidney, Peyer's
      patches, spleen, lung and thymus were processed for virological,
      histopathological and immunohistochemical examination. Apart from the two deaths,
      the experimental infection was inapparent, but virus was invariably recovered
      from faeces and several organs. The main histopathological lesions were focal
      interstitial pancreatitis, depletion of thymus and Peyer's patches, and
      interstitial pneumonia. Additionally, in the two mice that died, multifocal
      interstitial myocarditis was observed. EMCV antigen was detected in the cytoplasm
      of pancreatic acinar cells and in macrophages of the lung and the thymus. Antigen
      was also detected in the cytoplasm of cardiac muscle cells from three animals,
      including the two that died. The results support the role of mice, in addition to
      rats, as reservoir hosts in the epidemiology of EMCV infections on pig farms.

PMID- 16952371
TI  - Expect the unexpected or caveat for drug designers: multiple structure
      determinations using aldose reductase crystals treated under varying soaking and
      co-crystallisation conditions.
AB  - In structure-based drug design, accurate crystal structure determination of
      protein-ligand complexes is of utmost importance in order to elucidate the
      binding characteristics of a putative lead to a given target. It is the starting
      point for further design hypotheses to predict novel leads with improved
      properties. Often, crystal structure determination is regarded as ultimate proof
      for ligand binding providing detailed insight into the specific binding mode of
      the ligand to the protein. This widely accepted practise relies on the assumption
      that the crystal structure of a given protein-ligand complex is unique and
      independent of the protocol applied to produce the crystals. We present two
      examples indicating that this assumption is not generally given, even though the
      composition of the mother liquid for crystallisation was kept unchanged: Multiple
      crystal structure determinations of aldose reductase complexes obtained under
      varying crystallisation protocols concerning soaking and crystallisation exposure
      times were performed resulting in a total of 17 complete data sets and ten
      refined crystal structures, eight in complex with zopolrestat and two complexed
      with tolrestat. In the first example, a flip of a peptide bond is observed,
      obviously depending on the crystallisation protocol with respect to soaking and
      co-crystallisation conditions. This peptide flip is accompanied by a rupture of
      an H-bond formed to the bound ligand zopolrestat. The indicated enhanced local
      mobility of the complex is in agreement with the results of molecular dynamics
      simulations. As a second example, the aldose reductase-tolrestat complex is
      studied. Unexpectedly, two structures could be obtained: one with one, and a
      second with four inhibitor molecules bound to the protein. They are located in
      and near the binding pocket facilitated by crystal packing effects. Accommodation
      of the four ligand molecules is accompanied by pronounced shifts concerning two
      helices interacting with the additional ligands.

PMID- 16952372
TI  - Structure of zebra fish HIUase: insights into evolution of an enzyme to a hormone
      transporter.
AB  - During early vertebrate evolution, a duplication event in the gene encoding 5
      hydroxyisourate hydrolase (HIUase), a widely distributed enzyme of purine
      metabolism, gave rise to transthyretin (TTR), a thyroid hormone transporter. We
      report here on the crystal structure of zebra fish HIUase in two different
      crystal forms. Despite the phylogenetic distance, this structure compares well
      with those of newly characterized bacterial HIUases, especially with regard to
      catalytic regions, which are highly preserved. Comparison with TTR structure
      reveals a highly conserved scaffold, harbouring distinct functional sites located
      in the same regions of the two vertebrate proteins. Residues that are
      differentially conserved in HIUases compared to TTR map in putative catalytic
      regions occupying significant portions of the two halves of a central channel
      that transverses the whole TTR protein. The evolution of TTR has been accompanied
      by remarkable changes of the HIUase active sites that gave rise to a channel open
      at both ends, thus allowing free access to hormone molecules.

PMID- 16952373
TI  - PAS domain allostery and light-induced conformational changes in photoactive
      yellow protein upon I2 intermediate formation, probed with enhanced
      hydrogen/deuterium exchange mass spectrometry.
AB  - Photoactive yellow protein (PYP) is a small bacterial photoreceptor that
      undergoes a light-activated reaction cycle. PYP is also the prototypical Per-Arnt
      Sim (PAS) domain. PAS domains, found in diverse multi-domain proteins from
      bacteria to humans, mediate protein-protein interactions and function as sensors
      and signal transducers. Here, we investigate conformational and dynamic changes
      in solution in wild-type PYP upon formation of the long-lived putative signaling
      intermediate I2 with enhanced hydrogen/deuterium exchange mass spectrometry
      (DXMS). The DXMS results showed that the central beta-sheet remains stable but
      specific external protein segments become strongly deprotected. Light-induced
      disruption of the dark-state hydrogen bonding network in I2 produces increased
      flexibility and opening of PAS core helices alpha3 and alpha4, releases the beta4
      beta5 hairpin, and propagates conformational changes to the central beta-sheet.
      Surprisingly, the first approximately 10 N-terminal residues, which are essential
      for fast dark-state recovery from I2, become more protected. By combining the
      DXMS results with our crystallographic structures, which reveal detailed changes
      near the chromophore but limited protein conformational change, we propose a
      mechanism for I2 state formation. This mechanism integrates the results from
      diverse biophysical studies of PYP, and links an allosteric T to R-state
      conformational transition to three pathways for signal propagation within the PYP
      fold. On the basis of the observed changes in PYP plus commonalities shared among
      PAS domain proteins, we further propose that PAS domains share this
      conformational mechanism, which explains the versatile signal transduction
      properties of the structurally conserved PYP/PAS module by framework-encoded
      allostery.

PMID- 16952374
TI  - Structure of the Blm10-20 S proteasome complex by cryo-electron microscopy.
      Insights into the mechanism of activation of mature yeast proteasomes.
AB  - The 20 S proteasome is regulated at multiple levels including association with
      endogenous activators. Two activators have been described for the yeast 20 S
      proteasome: the 19 S regulatory particle and the Blm10 protein. The sequence of
      Blm10 is 20% identical to the mammalian PA200 protein. Recent studies have shown
      that the sequences of Blm10 and PA200 each contain multiple HEAT-repeats and that
      each binds to the ends of mature proteasomes, suggesting a common structural and
      biochemical function. In order to advance structural studies, we have developed
      an efficient purification method that produces high yields of stoichiometric
      Blm10-mature yeast 20 S proteasome complexes and we constructed a three
      dimensional (3D) model of the Blm10-20 S complex from cryo-electron microscopy
      images. This reconstruction shows that Blm10 binds in a defined orientation to
      both ends of the 20 S particle and contacts all the proteasome alpha subunits.
      Blm10 displays the solenoid folding predicted by the presence of multiple HEAT
      like repeats and the axial gates on the alpha rings of the proteasome appear to
      be open in the complex. We also performed a genetic analysis in an effort to
      identify the physiological role of Blm10. These experiments, however, did not
      reveal a robust phenotype upon gene deletion, overexpression, or in a screen for
      synthetic effects. This leaves the physiological role of Blm10 unresolved, but
      challenges earlier findings of a role in DNA repair.

PMID- 16952375
TI  - Fate determination of the flavin photoreceptions in the cyanobacterial blue light
      receptor TePixD (Tll0078).
AB  - PixD (Tll0078, Slr1694) is a BLUF (sensor of blue light using FAD)-type blue
      light receptor protein of the thermophilic cyanobacterium Thermosynechococcus
      elongatus BP-1 and the mesophilic cyanobacterium Synechocystis sp. PCC 6803. BLUF
      protein is known to show light-induced approximately 10 nm red shift of flavin
      absorption that is coupled with strengthening of the hydrogen bond between the
      O(4) of the isoalloxazine ring and a certain amino acid residue. According to the
      3D structure of TePixD we determined, O(4) of the ring is linked to Gln50 and
      Asn32. A survey of flavin-interacting residues by site-directed mutagenesis
      showed that Gln50 but not Asn32 is essential for the normal red-shifting
      photoreaction. Here, we further studied the role of Gln50 and its close neighbor
      Tyr8. All the mutated proteins of Gln50 and Tyr8 (Q50A, Q50N, Y8A and Y8F) lost
      the normal red-shifting photoreaction. Y8A, Y8F and Q50N, instead, showed a light
      induced flavin triplet state and a low yield of subsequent flavin reduction that
      is analogous to the photocycle of the LOV (light-oxygen-voltage-sensing) domain
      of phototropins, while Q50A did not. Fourier-transform infrared (FT-IR) analysis
      of N32A showed that O(4) of the ring is hydrogen-bonded to Asn32 both in the
      light and dark. These results, together with the 3D structure, indicate that the
      hydrogen bond network of Tyr8-Gln50-O(4)/N(5) (flavin) is critical for the light
      reaction of the BLUF domain. Based on the structural and functional similarities
      of the BLUF and the LOV domain of phototropins, we propose that the interaction
      between apoprotein and N(5) of flavin determines the photoreaction of the flavin
      binding sensors.

PMID- 16952376
TI  - Cold-induced sweating syndrome: a report of two cases and demonstration of
      genetic heterogeneity.
AB  - OBJECTIVES: To characterize the specific autonomic disturbances underlying the
      cold-induced sweating syndrome (CISS), and to describe a novel genetic variant of
      this rare recessive disorder. The two not previously reported patients had
      similar dysmorphic features: abnormal facial appearance, high arched palate, low
      set rotated ears, flexion deformities of elbows and fingers and scoliosis. Most
      noticeable were their paradoxical sweat responses: cold ambient temperature
      induced a profuse sweating over the face, arms and trunk but not over the lower
      limbs; while in the heat very little sweating occurred primarily on the legs.
      Testing of autonomic functions demonstrated normal cardiovascular reflexes and
      postganglionic sympathetic efferent functions. Sural nerve morphology and number
      of unmyelinated fibers was normal and skin biopsies showed normal appearing
      eccrine sweat glands. MRI scans revealed no structural brain abnormalities. Oral
      clonidine, prescribed in one patient, completely suppressed cold-induced
      sweating. Observed clinical features matched those of two sisters reported from
      Israel and of two brothers reported from Norway. All six cases presented a
      similar phenotype. The Norwegian, Israeli and Canadian cases were homozygous or
      compound heterozygous, respectively, for mutations in the CRLF1 gene on
      chromosome 19p12 (CISS1). The Australian case, however, had no pathogenic
      sequence variants in the CRLF1 gene, but was compound heterozygous for mutations
      in the CLCF1 gene on chromosome 11q13.3 (CISS2). CONCLUSION: The rare cold
      induced sweating syndrome is genetically heterogeneous and is probably caused by
      central and peripheral impairment of sudomotor functions. This is the first
      detailed report on the clinical consequences of mutations in the CLCF1 gene in
      humans. Directions for medical therapies are outlined to achieve long term
      symptom control.

PMID- 16952377
TI  - Walking through protein sequence space.
AB  - Following the original idea of Maynard Smith on evolution of the protein sequence
      space, a novel tool is developed that allows the "space walk", from one sequence
      to its likely evolutionary relative and further on. At a given threshold of
      identity between consecutive steps, the walks of many steps are possible. The
      sequences at the ends of the walks may substantially differ from one another. In
      a sequence space of randomized (shuffled) sequences the walks are very short. The
      approach opens new perspectives for protein evolutionary studies and sequence
      annotation.

PMID- 16952378
TI  - N-acetylcysteine attenuates TNF-alpha induced changes in secretion of interleukin
      6, plasminogen activator inhibitor-1 and adiponectin from 3T3-L1 adipocytes.
AB  - TNF-alpha is a key molecule in obesity-related metabolic disturbances. This study
      was designed to determine whether N-acetylcysteine (NAC), an antioxidant,
      prevents the activation of nuclear factor-kappaB (NF-kappaB) by exogenously
      administered TNF-alpha in adipocytes, and whether such change affects the
      production of adipocytokines. The treatment of well-differentiated 3T3-L1 cells
      with 20 mM of NAC significantly increased the reduced glutathione concentration
      up to 150% of control. The treatment with 10 ng/ml of TNF-alpha decreased
      antioxidant enzyme levels such as CuZn-superoxide dismutase (SOD), MnSOD and
      catalase, and activated NF-kappaB in 3T3-L1 adipocytes. The activation of NF
      kappaB was significantly prevented by the pretreatment with 20 mM of NAC. TNF
      alpha (1-10 ng/ml) dose-dependently increased interleukin (IL)-6 and plasminogen
      activator inhibitor-1 (PAI-1) secretion from 3T3-L1 adipocytes, while decreased
      adiponectin secretion. NAC (5-20 mM) attenuated the TNF-alpha-induced changes in
      these adipocytokine secretions in a dose-dependent manner. The effect of TNF
      alpha and NAC on the adipocytokine productions was exerted at the m-RNA level,
      judging from results of the real time RT-PCR analysis. The present study revealed
      that NAC inhibited the TNF-alpha-mediated activation of NF-kappaB and improved
      the adverse changes in the levels of IL-6, PAI-1 and adiponectin in 3T3-L1
      adipocytes. NAC may have the potential to improve the obesity-related abnormal
      adipocytokine metabolism by attenuating the TNF-alpha-induced oxidant-antioxidant
      imbalance in adipocytes.

PMID- 16952379
TI  - Expression of transforming growth factor beta (TGF-b1) by human preterm lung
      inflammatory cells.
AB  - Using a previously published model of human BPD this study examines whether
      preterm lung inflammatory cells produce transforming growth factor beta 1 (TGF
      beta1), a cytokine pivotal in pathogenesis of bronchopulmonary dysplasia (BPD),
      and whether TGF-beta1 expression is regulated by inflammation. Lung inflammatory
      cells (neutrophils and macrophages) recovered in the broncho-alveolar (BAL) fluid
      of premature infants intubated for respiratory distress after birth expressed TGF
      b1 mRNA and protein. Total and bioactive TGF-beta1 were abundantly found in the
      BAL fluid of the same infants. In cell culture stimulation by lipopolysaccharide
      (LPS) did not result in any further expression of total or bioactive TGF-beta1 by
      neonatal lung inflammatory cells over constitutive concentrations. In conclusion,
      lung inflammatory cells from premature infants are a source of TGF-beta1 but LPS
      does not regulate TGF-b1 production in these cells.

PMID- 16952380
TI  - Non-steroidal anti-inflammatory agents, tolmetin and sulindac, inhibit liver
      tryptophan 2,3-dioxygenase activity and alter brain neurotransmitter levels.
AB  - Hepatic tryptophan 2,3-dioxygenase (TDO) is one of the rate-limiting enzymes in
      tryptophan catabolism and plays an important role in regulating the physiological
      flux of tryptophan into relevant metabolic pathways. In this study, we determined
      the effect of the non-steroidal anti-inflammatory agents, tolmetin and sulindac,
      on rat liver TDO activity and the subsequent changes in the hippocampal and
      striatal neurotransmitter levels. The amount of melatonin produced by the pineal
      gland was also measured using high performance liquid chromatography (HPLC).
      Treatment of rats with tolmetin or sulindac (5 mg/kg/bd for 5 days) significantly
      inhibited liver TDO activity. The results show that whilst tolmetin and sulindac
      increase serotonin levels in the hippocampus, these agents also significantly
      reduce dopamine levels in the striatum. Tolmetin, but not sulindac, increased the
      amount of melatonin produced by the pineal gland. The results of this study
      suggest that whilst tolmetin and sulindac may be beneficial for patients
      suffering from depression, these agents also have the potential to induce adverse
      effects in patients suffering with neurological disorders such as Parkinson's
      disease.

PMID- 16952381
TI  - Appetite suppression through delayed fat digestion.
AB  - High-fat diets are often associated with greater caloric intake and weight gain.
      Since satiety during fat intake is induced by fat in the intestine we
      investigated the efficiency of a lipid compound that retards fat digestion to
      regulate fat intake. We found this compound to reduce high-fat food intake, body
      weight and blood lipids in Sprague-Dawley rats, without causing steatorrhea. The
      absence of steatorrhea is explained by an increased pancreatic lipase/colipase
      secretion, compensating the impaired lipolysis by the added compound. The animals
      also had an elevated CCK secretion. The satiety for fat may be the consequence of
      elevated CCK and procolipase/enterostatin levels. We conclude that compounds can
      be found that delay intestinal fat digestion and control high-fat food intake
      through the release of satiety signals, without causing steatorrhea. The absence
      of steatorrhea makes such compounds advantageous over lipase inhibitors in the
      treatment of obesity.

PMID- 16952382
TI  - Evidence for nitrite reductase activity in intact mouse Leydig tumor cells.
AB  - Nitric oxide (NO) supposedly derived via L-arginine-NO synthase (NOS) pathway has
      been implicated in inhibiting steroidogenesis by binding the heme moiety of
      steroidogenic enzymes. Previously, nitrite, and to a lesser extent nitrate ions
      inhibited steroidogenesis via NO by hitherto unknown reduction mechanism.
      Recently, a putative mammalian nitrite reductase activity ascribed to complex III
      of mitochondrial respiratory chain complexes (MRCC) has been reported, where MRCC
      inhibitors reduced NO production from nitrite variably. We thus studied the
      effects of MRCC inhibitors on testosterone production in mouse Leydig tumor cells
      (MLTC-1) without (basal) or with human chorionic gonadotropin (hCG) stimulation.
      In stimulated MLTC-1, MRCC inhibitors decreased testosterone production, order
      being: complex III (antimycin A and myxothiazol) > complex I (rotenone) > complex
      II (thenoyltrifluoroacetone), while cAMP production increased inversely. In
      unstimulated MLTC-1, MRCC inhibitors in same order, increased basal testosterone
      production, which correlated inversely with the percentage inhibition of NO
      production, with one exception; while antimycin A did not inhibit NO production
      in the nitrite reductase study mentioned above, it increased basal testosterone
      production in the present study. While MLTC-1 expressed mRNA for endothelial and
      neuronal, but not inducible NOS, various stimulators and inhibitors of L-arginine
      NOS pathway had no effect on basal testosterone production in MLTC-1 or fresh
      Balb/c Leydig cells. Moreover, hCG increased nitrate uptake into MLTC-1, which
      suggests the gonadotropin aids nitrite and nitrate ions in their steroidogenesis
      inhibitory activity. In conclusion, this study supports the existence of a
      surrogate mammalian nitrite reductase and the dormancy of L-arginine-NOS pathway
      in MLTC-1.

PMID- 16952383
TI  - Regional specificity in deltamethrin induced cytochrome P450 expression in rat
      brain.
AB  - Oral administration of deltamethrin (5 mg/kg x7 or 15 or 21 days) was found to
      produce a time-dependent increase in the mRNA expression of xenobiotic
      metabolizing cytochrome P450 1A1 (CYP1A1), 1A2 and CYP2B1, 2B2 isoenzymes in rat
      brain. RT-PCR studies further showed that increase in the mRNA expression of
      these CYP isoenzymes observed after 21 days of exposure was region specific.
      Hippocampus exhibited maximum increase in the mRNA expression of CYP1A1, which
      was followed by pons-medulla, cerebellum and hypothalamus. The mRNA expression of
      CYP2B1 also exhibited maximum increase in the hypothalamus and hippocampus
      followed by almost similar increase in midbrain and cerebellum. In contrast, mRNA
      expression of CYP1A2 and CYP2B2, the constitutive isoenzymes exhibited relatively
      higher increase in pons-medulla, cerebellum and frontal cortex. Immunoblotting
      studies carried out with polyclonal antibody raised against rat liver CYP1A1/1A2
      or CYP2B1/2B2 isoenzymes also showed increase in immunoreactivity comigrating
      with CYP1A1/1A2 or 2B1/2B2 in the microsomal fractions isolated from hippocampus,
      hypothalamus and cerebellum of rat treated with deltamethrin. Though the exact
      relationship of the xenobiotic metabolizing CYPs with the physiological function
      of the brain is yet to be clearly understood, the increase in the mRNA expression
      of the CYPs in the brain regions that regulate specific brain functions affected
      by deltamethrin have further indicated that modulation of these CYPs could be
      associated with the various endogenous functions of the brain.

PMID- 16952384
TI  - Conotoxins down under.
AB  - In the four decades since toxinologists in Australia and elsewhere started to
      investigate the active constituents of venomous cone snails, a wealth of
      information has emerged on the various classes of peptides and proteins that make
      their venoms such potent bioactive cocktails. This article provides an overview
      of the current state of knowledge of these venom constituents, several of which
      are of interest as potential human therapeutics as a consequence of their high
      potency and exquisite target specificity. With the promise of as many as 50,000
      venom components across the entire Conus genus, many more interesting peptides
      can be anticipated.

PMID- 16952385
TI  - The marine biologist--Bob Endean.
AB  - Bob Endean was a dedicated marine biologist with an extensive knowledge of coral
      reef communities in the Great Barrier Reef and fauna in subtropical Queensland
      waters. He commenced a study of venomous and poisonous marine animals dangerous
      to man at a time when the field was new, employing a variety of techniques to
      investigate the venom apparatus, mode of delivery of venom or toxin, mode of
      toxic action on excitable tissues, and biochemistry of venom or toxin.
      Determination of the pharmacological properties of crude venom from Conus marine
      snails advanced characterization of conotoxins by later workers. A study of four
      types of nematocysts from the box-jellyfish Chironex fleckeri provided
      information as to their structure, function, and mechanism of discharge;
      myotoxins T1 and T2 were isolated from microbasic mastigophores. Endean studied
      poisonous stonefish (Synanceia trachynis) and, with Ann Cameron, scorpionfish
      (Notesthes robusta); investigations of ciguatera and of paralytic shellfish
      poisoning were initiated. He organized the collection of Australian frogs which
      led to the isolation of caerulein by Erspamer in Italy. Endean highlighted the
      ecological danger of the population explosion of the crown-of-thorns starfish
      (Acanthaster planci) and provided the impetus for the creation of the Great
      Barrier Reef Marine Park.

PMID- 16952386
TI  - Microcystin analysis in human sera and liver from human fatalities in Caruaru,
      Brazil 1996.
AB  - In 1996, an extensive exposure of Brazilian hemodialysis patients at a dialysis
      center, using a municipal water supply water contaminated with cyanotoxins,
      provided the first evidence for acute lethal human poisoning from the cyclic
      peptide hepatotoxins called microcystins. During this outbreak, 100 of 131
      patients developed acute liver failure and 52 of these victims were confirmed to
      have been exposed to lethal levels of microcystins. Detection and quantitation of
      microcystins in these biological samples posed some analytical challenges since
      there were no well-established and routine analytic methods to measure total
      microcystins in tissue or sera samples. At the time of the 1996 exposure we used
      analytic methods that combined the use of enzyme linked immunosorbant assay
      (ELISA), analytical high performance liquid chromatography (HPLC), electrospray
      ionization ion-trap mass spectroscopy (ES-ITMS) and matrix assisted laser
      desorption ionization-time of flight spectroscopy (MALDI-TOF). In the intervening
      years these methods have been improved and others developed that allow a more
      quantitative and critical analysis of microcystin contaminated tissue and sera.
      For these reasons, and to see how storage with time might effect the detection
      and stability of microcystins in these matrices, we reanalyzed selected liver
      tissues and sera from the Caruaru victims in Brazil. We developed and validated a
      procedure to measure total microcystins in Caruaru human sera and liver tissue
      using a combination of ELISA, liquid chromatography and liquid chromatography
      mass spectrometry (LC/MS), GC/MS and MS/MS techniques. GC/MS and LC/MS were
      followed by MS/MS to obtain a fingerprint fragment spectra for the microcystins.
      The validity of the extraction procedure for free microcystins was confirmed by
      recovery experiments with blood sera spiked with microcystin-LR. We removed
      proteins with the Microcon Centrifugal Filter prior to LC/MS and ELISA analysis.
      A solid phase extraction (SPE) procedure was used for analysis of protein bound
      microcystins by conversion of ADDA to erythro-2-methyl-3-methoxy-4-phenylbutyric
      acid (MMPB) combined with GC/MS. We found that the GC/MS method yielded a higher
      concentration of microcystin than that obtained by ELISA and LC/MS. We
      hypothesize that this difference is due to better GC/MS detection of the
      covalently bound form of microcystins in human liver tissue. We also concluded
      that microcystins are very stable when stored under these conditions for periods
      of almost 10 years.

PMID- 16952387
TI  - Coupling reverse osmosis with electrodialysis to isolate natural organic matter
      from fresh waters.
AB  - Reverse osmosis (RO) has proven to be an effective method for the concentration
      of natural organic matter (NOM) from fresh waters, but an undesirable consequence
      of this process is the co-concentration of some inorganic solutes. Accordingly,
      current practice yields solutions of NOM that, upon desalting and freeze-drying,
      are converted into dry solids containing finely dispersed sulfuric acid and
      silicic acid (H(4)SiO(4)). These acids will contribute to the apparent carboxylic
      and phenolic contents of NOM, leading to an overestimation of both. NOM may also
      be chemically altered by sulfuric acid, which reacts strongly with many classes
      of organic compounds. The sulfur content and ash content of NOM will be elevated
      in the presence of sulfuric acid and H(4)SiO(4). The goal of this study is to
      develop and test a method in which the removal of water by RO is coupled with the
      removal of salts by electrodialysis (ED). Like RO, ED is a relatively mild
      treatment that enables the desalting of NOM solutions without subjecting those
      samples to conditions of extremely high or low pH. The end product of the coupled
      process is a desalted, concentrated liquid sample from which low-ash NOM can be
      obtained as a freeze-dried solid material. In this study, the efficacy of ED for
      desalting NOM is evaluated using concentrated synthetic river waters and actual
      concentrated (by RO) river waters. Under optimal operating conditions, both
      sulfate and silica can be largely removed from RO-concentrated solutions of
      riverine NOM with only an average loss of 3% of total organic carbon.

PMID- 16952388
TI  - Influence of loosely bound extracellular polymeric substances (EPS) on the
      flocculation, sedimentation and dewaterability of activated sludge.
AB  - Laboratory experiments on the activated sludge (AS) process were carried out to
      investigate the influence of microbial extracellular polymeric substances (EPS),
      including loosely bound EPS (LB-EPS) and tightly bound EPS (TB-EPS), on biomass
      flocculation, sludge settlement and dewaterability. The heat EPS extraction
      method was modified to include a mild step and a harsh step for extracting the LB
      EPS and TB-EPS, respectively, from the sludge suspension. Six lab-scale AS
      reactors were used to grow AS with different carbon sources of glucose and sodium
      acetate, and different sludge retention times (SRTs) of 5, 10 and 20 days. The
      variation in the bioreactor condition produced sludge with different abundances
      of EPS and different flocculation and separation characteristics. The sludge that
      was fed on glucose had more EPS than the sludge that was fed on acetate. For any
      of the feeding substrates, the sludge had a nearly consistent TB-EPS value
      regardless of the SRT, and an LB-EPS content that decreased with the SRT. The
      acetate-fed sludge performed better than the glucose-fed sludge in terms of
      bioflocculation, sludge sedimentation and compression, and sludge dewaterability.
      The sludge flocculation and separation improved considerably as the SRT
      lengthened. The results demonstrate that the LB-EPS had a negative effect on
      bioflocculation and sludge-water separation. The parameters for the performance
      of sludge-water separation were much more closely correlated with the amount of
      LB-EPS than with the amount of TB-EPS. It is argued that although EPS is
      essential to sludge floc formation, excessive EPS in the form of LB-EPS could
      weaken cell attachment and the floc structure, resulting in poor bioflocculation,
      greater cell erosion and retarded sludge-water separation.

PMID- 16952389
TI  - Plenary discussion--Experimental studies sessions I and II.

PMID- 16952390
TI  - Re: neoadjuvant chemotheraphy followed by vaginal radical trachelectomy in bulky
      stage IB1 cervical cancer.

PMID- 16952391
TI  - Isolated lymph node relapse of epithelial ovarian carcinoma: outcomes and
      prognostic factors.
AB  - BACKGROUND: Relapses of epithelial ovarian carcinoma (EOC) have a poor prognosis.
      Isolated lymph node relapses (ILNR) are considered of relatively good prognosis
      with intensive therapy. METHODS: This retrospective study aimed to describe
      incidence, characteristics, outcomes and prognostic factors of ILNR treated over
      15 years. RESULTS: Twenty-seven patients (4.2%) experienced an ILNR among 640
      patients. Median age was 59 years, tumour stages included stage I (n=4), II
      (n=5), III (n=15) and IV (n=3). After initial optimal treatment, median
      progression-free survival (PFS) was 26 months. Sites of relapse were
      retroperitoneum (n=15), left supraclavicular (n=7), mediastinum (n=4), iliac
      (n=4) and inguinal (n=3). ILNR locations were unique in 63% of patients (n=17)
      and multiple in 37% (n=10). Treatment modalities were surgery in eight patients
      (30%), chemotherapy in 15 (55%) and radiotherapy in 5 patients (18%), alone or in
      combination. Seven patients without tumour-related symptoms (26%) were not
      treated. Median overall survival (OS) after ILNR was 26 months. Median OS from
      initial diagnosis was 68 months. 25% of patients had a very long survival (>100
      months), independent of their initial staging or PFS. There was no difference in
      2-year survival after ILNR between the groups of early relapse (before 24 months)
      and late relapse (after 24 months). In the seven non-treated patients, median OS
      was 91 months. CONCLUSION: ILNR is a rare event in EOC. Time to relapse may not
      have its usual prognostic value. Immediate or delayed therapy should be discussed
      in case of asymptomatic ILNR.

PMID- 16952392
TI  - Sib-size, birth order and risk of overweight in junior high school students in
      Japan: results of the Toyama Birth Cohort Study.
AB  - OBJECTIVE: To investigate whether there is a relationship between sib-size, birth
      order and the risk of overweight in junior high school students. METHOD: Sib
      size, birth order, height and weight of subjects and their parents, and other
      lifestyle factors were obtained through a questionnaire survey conducted between
      June and July 2002 from 7,959 junior high students in Toyama prefecture, Japan.
      Logistic regression analysis was performed to examine the associations. Boys and
      girls were analyzed separately. RESULTS: Boys from three-child families showed a
      significantly lower risk of overweight than only boys (odds ratio (OR)=0.66,
      p=0.010), and girls from larger families have a significantly lower risk than
      only girls (p for trend=0.001). Compared to middle-born girls, only girls have a
      significantly higher risk of overweight (OR=2.22, p<0.001). The risk of
      overweight in boys was significantly lower with increasing number of elder
      sibling or sister. However, increasing of any one sibling almost had the same
      risk reduction effect on the risk of overweight in girls (OR ranged from 0.74 to
      0.76, p<=0.001). CONCLUSION: Children without siblings are the ones most at risk
      for overweight, especially in girls. Birth order and sib-size are possible risk
      factors for the development of overweight and obesity.

PMID- 16952393
TI  - Modulation of the human bone cell cycle by calcium ion-implantation of titanium.
AB  - Ca ion implantation of Ti surfaces has previously been reported to enhances
      osseointegration in vivo. Although the mechanisms underlying the response of bone
      cells to these novel surfaces still remain unclear, it is possible that Ca ion
      implanted Ti (Ca-Ti) may influence the growth of new bone by modulating the
      progression of the cell cycle. In the present study we have, therefore, examined
      the precise effects of Ca ion-implantation of Ti on the bone-like MG-63 cell line
      in vitro. The results of flow cytometry analysis showed that this surface
      markedly enhanced the proportion of cells which expressed Ki-67, a cell
      proliferation-associated nuclear antigen, compared with cells grown on the non
      implanted Ti (control) surface. In addition, cultures grown on Ca-Ti and
      synchronized at the G1/S boundary by hydroxyurea more rapidly re-entered and
      progressed through the S and G2/M phases of the cell cycle than their
      counterparts on Ti. Ca ion-implantation also significantly increased the numbers
      of mitotic cells. These results thus show that alteration of the surface
      chemistry of Ti by high-energy implantation with Ca ion was able to substantially
      modulate the progression of the bone cell cycle, and suggest a possible means of
      enhancing the response of bone cells to implant materials.

PMID- 16952394
TI  - The effect of oxygen plasma pretreatment and incubation in modified simulated
      body fluids on the formation of bone-like apatite on poly(lactide-co-glycolide)
      (70/30).
AB  - In this study, biodegradable poly(lactide-co-glycolide) (PLGA) (70/30) films and
      scaffolds were first treated with oxygen plasma and then incubated in a modified
      simulated body fluid 1.5SBF0 to prepare a bone-like apatite layer. The formation
      of the apatite and its influence on osteoblast-like cells growth were
      investigated. It was found that the bone-like apatite formability of PLGA(70/30)
      was enhanced by plasma pretreatment. The changes of surface chemistry and surface
      topography induced by oxygen plasma treatment were both effective for apatite
      formation. The apatite formability increased with increasing plasma-treating
      time. Under a treating condition of 20 W for 30 min, oxygen plasma treatment
      could penetrate into the inner scaffold. After 6 days incubation, the apatite
      formed in plasma-treated scaffold was better distributed than in untreated
      scaffold, and the weight and mechanical strength of the plasma-treated scaffold
      were both enhanced. Compared with PLGA(70/30), the apatite layer formed on oxygen
      plasma-treated PLGA(70/30) surface enhanced adhesion and proliferation of OCT-1
      osteoblast-like cell, but had no significant effect on cell's ALP activity at day
      7. A prolonged investigation is being in process to further verify the bone-like
      apatite effects on osteogenic differentiation.

PMID- 16952395
TI  - The effect of adsorbed serum proteins, RGD and proteoglycan-binding peptides on
      the adhesion of mesenchymal stem cells to hydroxyapatite.
AB  - Prior studies from our laboratory have shown that RGD peptides increase the
      attachment of mesenchymal stem cells (MSCs) to hydroxyapatite (HA), however, RGD
      does not induce cell spreading when coupled to this type of biomaterial. In an
      effort to improve MSC spreading, and possibly cell attachment, proteoglycan
      binding peptides (KRSR or FHRRIKA) were combined with RGD in the current study.
      It was found that the peptide combinations did not enhance MSC attachment
      relative to RGD alone, although a slight amount of spreading was elicited by both
      KRSR and FHRRIKA. Similar results were obtained with proteoglycan-binding
      peptides modified with a heptaglutamate domain, a motif that improves peptide
      tethering to HA. To determine whether differentiation status affected cell
      responses, MSCs were in vitro differentiated into osteoblasts, and evaluated as
      before. These experiments revealed that, like MSCs, osteoblasts did not adhere in
      greater numbers to the peptide combinations. Finally, none of the peptides or
      peptide combinations were able to stimulate the robust amount of cell adhesion
      and spreading elicited by serum-coated HA surfaces (of note, five different
      species of serum were tested). Given the propensity of HA to adsorb proadhesive
      proteins from blood/serum, we question the utility of functionalizing HA with RGD
      and/or proteoglycan-binding peptides.

PMID- 16952396
TI  - Characterizing short-term release and neovascularization potential of multi
      protein growth supplement delivered via alginate hollow fiber devices.
AB  - Multi-protein (10-250 kDa) endothelial cell growth supplement (ECGS) contains
      growth factors of varying sizes resulting in advanced release rates from
      diffusion-based drug delivery devices. As a result, the biochemical stimulus
      provided by ECGS for neovascularization in the critical initial stages of cell
      transplantation in artificial organs may differ from that for single growth
      factor delivery. In this study, both in vitro and in vivo studies were conducted
      with ECGS to correlate in vitro release of multiple angiogenic growth factors to
      vascularization potential in vivo. The short-term release of ECGS from calcium
      alginate gels supported in the lumen of polypropylene (PP) hollow fibers was
      investigated in vitro for up to 142 h. The overall time constant increased from
      2, 2.2 and 6.3 h as the alginate concentration was increased from 1.5%, 2% and
      3%, respectively. However, time constants for individual species ranged from 1.5
      to 77 h. The in vivo bioactivity of released ECGS was assessed for up to 21 days
      using a Lewis rat model implanted with 1.5% calcium alginate gels supported in PP
      and polysulfone hollow fibers. For the ECGS-releasing PP hollow fiber system, a
      two-fold increase in neovascularization with respect to the control was observed
      for the period between 7 and 17 days post-implantation at the device-tissue
      interface (p<0.05).

PMID- 16952397
TI  - Outcomes of vitrectomy with inferior retinectomy in patients with recurrent
      rhegmatogenous retinal detachments and proliferative vitreoretinopathy.
AB  - PURPOSE: To report the anatomic and functional outcomes of patients treated with
      vitrectomy and inferior retinectomy for recurrent, rhegmatogenous retinal
      detachment complicated by proliferative vitreoretinopathy (PVR). DESIGN:
      Retrospective, noncomparative, interventional case series. PARTICIPANTS: Fifty
      six patients with recurrent, rhegmatogenous retinal detachments complicated by
      PVR who underwent an inferior retinectomy for repair. METHODS: Retrospective
      review over a 6-year period of patients treated with vitrectomy and inferior
      retinectomy. MAIN OUTCOME MEASURES: The primary outcome was anatomic success,
      defined as complete retinal reattachment. Secondary outcomes included change in
      visual acuity, the mean number of operations required for complete retinal
      reattachment, number of operations before retinectomy, use of silicone oil
      tamponade, location and extent of retinectomy, whether lensectomy was undertaken,
      and incidence of postoperative complications. RESULTS: Complete retinal
      reattachment was achieved in 52 of 56 patients (93%), with a mean follow-up of 25
      months (range, 6-70 months). After retinal reattachment, visual acuity was
      improved or stabilized in 39 of 56 patients (70%). The mean number of operations
      for retinal detachment before diagnosis of PVR requiring retinectomy was 1.8
      (range, 1-5). Patients undergoing radical anterior vitreous base dissection and
      lensectomy at the time of first retinectomy had a higher success rate than those
      who did not: 74% versus 38%, respectively (P = 0.011). Furthermore, tamponade
      with silicone oil had a higher success rate than tamponade with gas: 71% versus
      18%, respectively (P = 0.002). Of the 56 patients, 9 (16%) had 1 or more of the
      following complications: keratopathy requiring penetrating keratoplasty (n = 4),
      glaucoma requiring aqueous shunt device (n = 3), and hypotony (n = 3). Silicone
      oil removal was performed in 26 of 45 patients (58%) before the last follow-up
      visit, with a 1 in 26 (4%) redetachment rate. CONCLUSIONS: When combined with
      anterior base dissection, inferior retinectomy may be useful in the surgical
      treatment of complex PVR-related retinal detachment. The authors show that with
      lensectomy, radical anterior base dissection, and inferior retinectomy, anatomic
      success rates are improved and visual function can be maintained. In addition,
      silicone oil offers an advantage over gas tamponade in these cases.

PMID- 16952398
TI  - A systematic review comparing the functional neuroanatomy of patients with
      depression who respond to placebo to those who recover spontaneously: is there a
      biological basis for the placebo effect in depression?
AB  - BACKGROUND: Functional neuroimaging research indicates that depression, and
      treatment, are associated with neurobiological changes. Changes associated with
      natural recovery or the placebo effect are unknown. The aim of this study is to
      assess whether the placebo effect in depression is associated with specific
      functional neuroimaging changes. METHOD: Systematic review of functional
      neuroimaging studies containing unipolar depressed patients. Subjects were
      either: in a placebo group, undergoing pre- and post-treatment scans and clinical
      ratings; or were treatment-free, and underwent two sets of scans and ratings.
      RESULTS: Of placebo group studies, 2 of 4 showed no specific changes; the others
      showed increased frontal activity on recovery. Of treatment-free studies, only 2
      out 5 had sufficient relevance; both showed increased anterior cingulate activity
      on recovery, one showed increased left DLPFC activity. LIMITATIONS:
      Methodological problems affected most of the studies found: low sample sizes,
      high inter-subject variability, and lack of design and data description for the
      question being asked in this review. There are limitations in comparing studies
      that differ in: subject type, neuroimaging technique, target site, trial design,
      and results. The fact that this systematic review was conducted by only one rater
      increases likelihood of bias. CONCLUSIONS: Recovery from depression in placebo
      groups correlates with changes in frontal and cingulate cortical activity,
      although these may also be found in recovery without treatment. It is also
      speculated that antidepressant treatment delay relates to 'counterbalancing' of
      an advantageous placebo effect with a disadvantageous initial drug effect.

PMID- 16952399
TI  - Cost-of-illness studies of depression: a systematic review.
AB  - BACKGROUND: Depression is a very common disease with substantial economic
      consequences. This paper reviews all published cost-of-illness studies of
      depression worldwide. METHODS: A systematic search of cost-of-illness studies of
      depression in the databases MEDLINE, Web of Science, Cochrane Library, and
      PSYNDEXplus was conducted. Identified studies were classified by their basic
      characteristics. Costs reported were inflated in original currency to the year
      2003 and then converted into US-dollar using purchasing power parities (US$ PPP).
      Additionally, national-costs were converted in costs per case and per inhabitant.
      RESULTS: 24 papers with notable methodical differences were identified and
      classified by their basic characteristics. Summary estimates from the studies for
      the average annual costs per case ranged from $1000 to $2500 for direct costs,
      from $2000 to $3700 for morbidity costs and from $200 to $400 for mortality
      costs. The basic quantity of interest in COI-studies of depression was stated.
      LIMITATIONS: Methodical differences limited comparison substantially.
      CONCLUSIONS: Depression is associated with a high economic burden. Conducting COI
      studies of depression along the line noted in the review could help provide the
      opportunity to expose differences in costs associated with different approaches
      to disease management.

PMID- 16952400
TI  - Kynurenine pathway in major depression: evidence of impaired neuroprotection.
AB  - The neurodegeneration hypothesis proposed major depression as a consequence of
      the imbalance between neuroprotective and neurodegenerative metabolites in the
      kynurenine pathway. To test the hypothesis, plasma tryptophan and kynurenine
      pathway metabolites were studied in 58 patients with major depression and 189
      normal controls. The mean tryptophan breakdown index was higher (p=0.036), and
      mean kynurenic acid concentration and mean neuroprotective ratios were lower, in
      depressed patients (p=0.003 and 0.003, respectively). In receiver operating
      characteristic analysis, the kynurenic acid concentrations and the
      neuroprotective ratio showed clear discrimination between depressed patients and
      controls with area under the curve 79% and 76.3% respectively. The
      neuroprotective ratio did not change after treatment in those with repeated
      episodes of depression but it increased significantly (p=0.044) in those with
      first episodes. The results suggested that the reduction in neuroprotective
      markers, which indicated an impaired neuroprotection, might play an important
      role in pathophysiology of major depression.

PMID- 16952401
TI  - Magnesium sulfate suppresses inflammatory responses by human umbilical vein
      endothelial cells (HuVECs) through the NFkappaB pathway.
AB  - Dysfunctional endothelial cell activation and cytokines are implicated in preterm
      labor, a condition commonly treated with the tocolytic agent, magnesium sulfate
      (MgSO(4)). Based on recent findings showing the inflammatory effects of magnesium
      deficiency, we examined the effect of MgSO(4) on human umbilical vein endothelial
      cell (HuVEC) inflammatory responses in vitro. HuVECs isolated from term umbilical
      cords were incubated with MgSO(4) prior to stimulation with lipopolysaccharide
      (LPS) and then assessed for endothelial cell activation. Endothelial cell
      supernatants were assayed for inflammatory mediator production (interleukin-8; IL
      8), and endothelial cell-associated intercellular adhesion molecule (ICAM-1)
      expression was determined. In the absence of LPS stimulation, MgSO(4) had no
      effect on HuVEC responses. Treatment of HuVECs with MgSO(4) prior to LPS
      stimulation inhibited inflammatory mediator production (p<0.05) and cell adhesion
      molecule expression (p<0.05) in a dose-dependent manner. Mechanistic studies
      showed that MgSO(4) reduced NFkappaB nuclear translocation and protected
      cytoplasmic IkappaBalpha from degradation in LPS-treated HuVECs. In conclusion,
      MgSO(4) inhibits endothelial cell activation, as measured by levels of IL-8 and
      ICAM-1 expression, via NFkappaB. Our results support the hypothesis that MgSO(4)
      treatment may function as an anti-inflammatory agent during preterm labor.

PMID- 16952402
TI  - Double depression in adult psychiatric outpatients in Brazil: distinct from major
      depression?
AB  - This study examines whether distinct symptom profiles, patterns of comorbidity,
      and suicidal symptoms uniquely characterize individuals diagnosed with double
      depression (DD) by comparing Brazilians with DD to those with major depressive
      disorder (MDD). One hundred forty two psychiatric outpatients (ages 20-77
      mean=48.8, S.D.=13.2; DD, n=23; MDD, n=119) participated in structured diagnostic
      interviews and completed self-report measures of depressive symptoms,
      suicidality, and family history of mental disorders. Patients with DD exhibited a
      more severe symptom profile than those with MDD, as evidenced by a higher number
      of depressive symptoms and more intense suicidal ideation. They also appeared to
      be qualitatively different from individuals with MDD, as evidenced by distinct
      comorbidity patterns, quality of life reports, and anhedonic features. These
      results may be important in understanding the phenomenology of DD in psychiatric
      outpatients by informing diagnostics, psychotherapy, and psychotherapeutic
      treatment of DD.

PMID- 16952403
TI  - Comparative study of the anti-inflammatory effect of two intravenous
      immunoglobulin preparations manufactured by different processes.
AB  - Intravenous immunoglobulin (IVIG) is increasingly used in the treatment of
      diverse immune-mediated disorders. Since several preparations of IVIG are
      available for therapy, it is possible that different manufacturing processes
      might influence clinical efficacy of IVIG. An insight into the mechanisms of
      action of such different IVIG preparations is therefore necessary that will
      provide further guidelines for the utility of IVIG preparations in autoimmune and
      inflammatory diseases. Since endothelial cells (EC) influence the inflammatory
      process via production of cytokines, chemokines and expression of adhesive
      molecules, we analyzed the anti-inflammatory effect on EC of two IVIG
      preparations: caprylated IVIG (IVIG-C) versus solvent/detergent-treated IVIG
      (IVIG-SD) preparation. We found that both IVIG preparations inhibit in an
      equivalent manner, the expression of different pro-inflammatory factors such as
      IL-6, IL-8, GM-CSF, IL-1beta and TNF-alpha and the adhesion molecules ICAM-1 and
      VCAM-1. Our results thus suggest that the caprylate while inactivating the virus
      and enhancing the yield of IgG during IVIG formulation, does not modulate the
      immunomodulatory properties of IVIG at EC level and that the two preparations
      show similar anti-inflammatory effects.

PMID- 16952404
TI  - Accumulation of class switched IgD-IgM- memory B cells in the cerebrospinal fluid
      during neuroinflammation.
AB  - Inflammatory diseases of the central nervous system (CNS) are characterized by
      cerebrospinal fluid (CSF) pleocytosis often involving the recruitment of B cells.
      Little is still known about B cells that are found in the CSF during
      neuroinflammation. To address the phenotype of these B cells, we studied the
      distribution of the major B cell subsets in peripheral blood (PB) and CSF of 25
      patients with inflammatory diseases of the nervous system by flow cytometry. Six
      different B cell subsets were identified in PB and CSF according to the surface
      expression of IgM, IgD, CD27 and CD19. In all patients analysed, memory B cells
      outnumbered naive B cells in the CSF, whereas naive B cells were more prevalent
      in PB. The accumulation of memory B cells in the CSF was largely due to the
      recruitment of IgM-IgD- class switched memory B cells. The distribution of
      IgM+IgD+, IgM-IgD+, IgM+IgD- memory cells and immature cells did not differ
      significantly between CSF and PB. These findings demonstrate a selective
      recruitment of IgM-IgD- memory B cells to the CSF suggesting a specific role of
      these cells during neuroinflammation.

PMID- 16952405
TI  - Bone marrow derived mast cell acquire responsiveness to substance P with Ca(2+)
      signals and release of leukotriene B(4) via mitogen-activated protein kinase.
AB  - Substance P (SP) selectively activates mast cells that reside in connective
      tissues. We studied the reactions of bone marrow-derived mast cells (BMMC) of
      three mouse strains, cultured with or without fibroblasts. BMMC co-cultured with
      fibroblasts, but not those cultured alone, increased intracellular Ca(2+),
      released LTB(4) and histamine in response to SP. PD098059 significantly inhibited
      the release of LTB(4), but not histamine in all strains. SB203580 failed to
      reduce or slightly impaired the release of LTB(4). These results suggest that
      mast cells undergo maturation under the influence of fibroblasts, acquiring the
      responsiveness to SP with Ca(2+) signals and predominantly ERK-MAP kinase.

PMID- 16952406
TI  - Two patients with the V37I/235delC genotype: are radiographic cochlear anomalies
      part of the phenotype?
AB  - We present two East Asian patients with sensorineural hearing loss (SNHL) and
      compound heterozygosity for the 235delC and V37I mutations in the GJB2 gene. One
      patient has a unilaterally enlarged vestibular aqueduct, which underscores the
      importance of routine CT examination in children with SNHL, even if GJB2
      (connexin 26) mutations have been identified. The second patient was not
      available for evaluation by CT. The pathogenic role of the V37I mutation has been
      controversial. We review the literature and present evidence in support of
      pathogenicity. Larger studies in compound heterozygous individuals and co
      transfection studies will allow better genotype-phenotype correlations and
      prognostication.

PMID- 16952407
TI  - Elevated anxiety-like and depressive behavior in Desert hedgehog knockout male
      mice.
AB  - To investigate the functional role of Desert hedgehog (Dhh) gene in the nervous
      system, we examined motor, sensory, learning and memory functions as well as mood
      in Dhh knockout (KO) mice. Dhh KO male mice exhibited prolonged immobility time
      compared with wild-type male mice in the forced swimming test, and showed
      enhanced inhibition in the Vogel's conflict model. These findings suggest that
      Dhh KO male mice exhibited enhanced anxiety and depressive behavior compared with
      wild-type male mice. In contrast, Dhh KO female mice did not show any significant
      difference compared to wild-type female mice. These behavioral abnormalities of
      Dhh KO male mice may be due to lower testosterone levels with abnormal
      development of the testes caused by Dhh-null mutation.

PMID- 16952408
TI  - Thymopentin (TP5), an immunomodulatory peptide, suppresses proliferation and
      induces differentiation in HL-60 cells.
AB  - Thymopentin (Arg-Lys-Asp-Val-Tyr, TP5) has shown immuno-regulatory activities in
      humans. In the present study, we investigated the effects of TP5 on the
      proliferation and differentiation of a human promyelocyte leukemia cell line, HL
      60. It is noteworthy that TP5 displayed concentration-dependent inhibitory
      effects on the proliferation and colony formation of HL-60 cells. Furthermore,
      the decrease or even disappearance of AgNORs from nucleoli was observed in HL-60
      cells after the treatment with TP5. The suppression induced by TP5 was
      accompanied by an accumulation of cell cycle in the G0/G1 phase. Moreover, TP5
      significantly increased the NBT-reduction activity of HL-60 cells.
      Cytofluorometric and morphologic analysis indicated that TP5 had induced
      differentiation along the granulocytes lineage in HL-60 cells. d-tubocurarine
      (TUB) significantly antagonized the inhibitory effects induced by TP5, whereas
      atropine did not exhibit such effect. All the results indicated that TP5 was able
      to significantly inhibit proliferation and induce differentiation in HL-60 cells.
      Our observations also implied that TP5 not only acted as an immunomodulatory
      factor in cancer chemotherapy, but is also a potential chemotherapeutic agent in
      the human leukemia therapy.

PMID- 16952409
TI  - Importance of bacterial surface properties to control the stability of emulsions.
AB  - In colloidal media such as emulsions or food matrixes, the stability results from
      physicochemical interactions. The same type of interaction is involved in the
      attachment processes of microorganisms, through their surface properties, to
      interfaces. When bacteria are present in a food matrix, it is probable that their
      surface interacts with the other constituents. In this paper, the involvement of
      bacterial surface properties of Lactococcus lactis subsp lactis biovar
      diacetylactis (LLD) on the stability of model emulsions has been studied. The
      hydrophobic and electrostatic cell-surface properties were characterized by the
      MATH method and by microelectrophoresis, respectively. The oil-in-water emulsions
      were stabilized by various surface-active compounds, CTAB, SDS or Tween 20,
      giving differently charged droplets. Two strains with different surface
      characteristics were added to the emulsion. Contrasting with emulsions made with
      the non-ionic surfactant, for which the stability was not modified by the
      addition of bacteria, the emulsions made with ionic surface-active compounds were
      unstable in the presence of bacteria when the bacterial surface charge was
      opposite to the one of the emulsion droplets. Moreover, aggregation and
      flocculation phenomena were observed for emulsions stabilized with the cationic
      surfactant, particularly for more negatively charged bacteria. The effect of
      bacteria on the emulsion stability depended on the strain which shows the
      importance of the choice of the microorganism according to of the characteristics
      of the colloidal media to obtain a stable system. In addition, these results
      suggest that the interactions between bacteria and other food components can
      influence the position of bacteria in food matrixes.

PMID- 16952410
TI  - C-reactive protein and the risk of developing type 2 diabetes in Aboriginal
      Australians.
AB  - OBJECTIVE: To investigate the association between C-reactive protein (CRP) and
      the risk of developing diabetes in Aboriginal Australians. RESEARCH DESIGN AND
      METHODS: High sensitivity CRP levels were measured in 620 Aboriginal participants
      aged 20-74 years free from diabetes at baseline in a remote community in the
      Northern Territory of Australia. Participants were followed for a median of 11
      years to identify newly diagnosed cases of diabetes. Cox proportional hazards
      models were used to assess the relationship of CRP levels with the risk of
      developing diabetes over the follow-up period. RESULTS: A total of 109
      participants were newly diagnosed with diabetes. Incident rates were 10.8, 16.6
      and 28.8 per 1000 person-years for people in the lower, middle and upper tertile
      groups of baseline CRP levels, respectively. After adjusting for age, sex, BMI,
      baseline glucose regulation status, total cholesterol, urine albumin to
      creatinine ratio, systolic blood pressure, smoking and alcohol drinking, the
      association between diabetes and CRP remained significant, with a hazard ratio of
      1.23 (95% confidence interval (CI) 1.05, 1.45) corresponding to a doubling in CRP
      values. Similarly, the adjusted hazard ratio for development of diabetes in
      people in the upper tertile versus the bottom two tertiles of CRP was 1.75 (95%
      CI 1.19, 2.56). CONCLUSIONS: CRP is independently associated with the development
      of diabetes in Aboriginal people. Our findings support a role of inflammation in
      the etiology of diabetes in the high risk population of Aboriginal Australians.

PMID- 16952411
TI  - Presenilin-1 mutation E318G and familial Alzheimer's disease in the Italian
      population.
AB  - Presenilin-1 (PSEN-1) is a component of the gamma-secretase complex involved in
      beta-amyloid precursor protein (betaAPP) processing. To date about 140 pathogenic
      mutations in the PSEN-1 gene have been identified and their main biochemical
      effect is to increase the production of the fibrillogenic peptide Abeta(1-42). An
      exception is the PSEN-1 [E318G] mutation that does not alter Abeta(1-42)
      generation and is generally considered a non-pathogenic polymorphism.
      Nevertheless, this mutation was reported to be a genetic risk factor for familial
      Alzheimer's disease (FAD) in the Australian population. To independently confirm
      this indication, we performed a case-control association study in the Italian
      population. We found a significant association (p<0.05, Fisher's exact test)
      between the presence of PSEN-1 [E318G] and FAD. In addition, on measuring the
      Abeta(1-42) and Abeta(1-40) concentrations in fibroblast-conditioned media
      cultured from PSEN-1 [E318G] carriers and PSEN-1 [wild type] controls we noted a
      significant decrease (p<0.05, Mann-Whitney test) in the Abeta(1-42)/Abeta(1-40)
      ratio in PSEN-1 [E318G] carriers, suggesting a peculiar biochemical effect of
      this mutation.

PMID- 16952412
TI  - [Lymphoma with initial renal involvement: four cases].
AB  - PURPOSE: To present a comprehensive description of the clinical features of
      patients with renal manifestations during lymphoma. METHODS: Retrospective review
      of medical records from all patients diagnosed with lymphoma associated with
      kidney involvement in our hospital between 1996 to 2004. Four cases were
      identified and analysed. RESULTS: Four patients presented a non-Hodgkin's
      lymphoma. One patient showed intravascular large B-cell lymphoma, revealed by
      proteinuria. Another patient had a nephrotic syndrome, and two had a renal mass.
      Renal histology allowed diagnosis of lymphoma in 3 cases. CONCLUSION: The
      diagnosis of lymphoma associated with renal involvement is rather difficult, and
      more specifically in case of intravascular large B-cell lymphoma, or even primary
      renal lymphoma. We present here a comprehensive review of the literature and we
      discuss pathogenesis of these conditions.

PMID- 16952413
TI  - Depth profiles of radiocarbon and carbon isotopic compositions of organic matter
      and CO2 in a forest soil.
AB  - Depth profiles of the specific activities of (14)C and carbon isotopic
      compositions (Delta(14)C, delta(13)C) in soil organic matter and soil CO(2) in a
      Japanese larch forest were determined. For investigating the transport of CO(2)
      in soil, specific activities of (14)C, Delta(14)C and delta(13)C in the organic
      layer, and atmospheric CO(2) in the same forest area were also determined. The
      specific activity of (14)C and Delta(14)C in the soil organic matter decreased
      with the increase in depth of 0-60cm, while that of soil CO(2) did not vary
      greatly at a soil depth of 13-73cm and was more prevalent than that of
      atmospheric CO(2). Peaks of specific activities of (14)C appeared at the depth of
      0-4cm and Delta(14)C values were positive in the depth range from 0 to 15cm.
      These results suggest that the present soil at a depth of 0-4cm had been produced
      from the mid-1950s up until 1963, and the bomb C had reached the depth of 15cm in
      the objective soil area. The delta(13)C in the soil organic matter increased at
      the depth of 0-55cm, while that of soil CO(2) collected on 8 November 2004
      decreased rapidly at the depth of 0-13cm and only slightly at the depth of 53
      73cm. By combining the Delta(14)C and delta(13)C of the respective components and
      using the Keeling plot approach it was made clear that the entering of
      atmospheric CO(2) showed a large contribution to soil CO(2) at the depth of 0
      13cm and a negligible contribution at the depth of 53-73cm for soil air collected
      on 8 November 2004. Respiration of live roots was presumed to be the main source
      of soil CO(2) at the depth of 53-73cm on 8 November 2004.

PMID- 16952414
TI  - Childhood socioeconomic status and suicide mortality in early adulthood among
      Norwegian men and women. A prospective study of Norwegians born between 1955 and
      1965 followed for suicide from 1990 to 2001.
AB  - Even though the causes of suicide may be rooted in childhood, it is unknown how
      socioeconomic position (SEP) in childhood is related to suicide in adulthood. We
      describe the association between childhood SEP and suicide mortality in adulthood
      in Norway using registry data on 613807 Norwegians born in 1955-1965. Data on
      1013 suicide deaths between 1990 and 2001 were linked to data on SEP indicators,
      using Cox regression. Suicide mortality was higher among women with high
      childhood SEP than among women with low childhood SEP. This association was
      explained in part by family situation in adulthood, but not by adult SEP. For
      males, after adjustment for adult SEP, we observed a similar but weaker
      association between suicide and childhood SEP. We discuss several mechanisms
      which may explain the direct positive association of childhood SEP with suicide
      mortality in adulthood, especially among females. These are downward mobility,
      not meeting high demands set by highly educated parents, psychological distress,
      mental disorder, gender differences and social networks and norms.

PMID- 16952415
TI  - Perceptions of the environment, physical activity, and obesity.
AB  - Obesity rates are rising rapidly across the developed and developing world. Until
      recently obesity research has mainly focused on biological, psychological and
      behavioural factors. But there is growing agreement that environmental factors
      play an important role as well. In this study data from the 2003 Health Survey
      for England (n = 14,836) were analysed from a multilevel perspective to examine
      (1) the associations of the perceptions of the local environment with obesity,
      self-rated health, and physical activity, and (2) whether physical activity
      mediates the association between the perceptions of the environment, and obesity
      and self-rated health. This study found that perceptions of the friendliness of
      the local environment were mainly associated with self-rated health; perceived
      access to leisure facilities with sports activities; perceived access to a post
      office with walking; and the presence of social nuisances with obesity and poor
      self-rated health. In addition, positive perceptions of the social environment
      (i.e., social support and social capital) were associated with higher levels of
      physical activity, and lower levels of poor self-rated health and obesity. Only
      limited support was found for the idea that health behaviours mediate the
      associations between the perceptions of the environment, obesity, and self-rated
      health. Controlling for the three physical activity measures only rendered a
      small number of associations with self-rated health non-significant, and did not
      affect the associations with obesity. Overall, the results show that certain
      aspects of the environment may contribute to the risk of obesity and poor health.
      More research is needed to examine the specific mechanisms that link (the
      perceptions of) the environment to obesity and health.

PMID- 16952416
TI  - Inupiat youth suicide and culture loss: Changing community conversations for
      prevention.
AB  - Inupiat living in Northwest Alaska have one of the highest youth suicide rates in
      the world. Other circumpolar peoples share this disturbing distinction. This
      demographic and ethnic health disparity has spurred research that investigates
      acculturation stress as a cause of Inuit youth suicide. Despite this body of
      knowledge, few studies describe how local people connect suicide to culture loss,
      even though this understanding is crucial for developing effective prevention and
      intervention strategies. This article describes how Inupiat understand and talk
      about youth suicide and suicide prevention within public settings. I have used
      participatory action research (PAR) to illuminate the meanings and processes that
      surround youth suicide. In meetings focused on suicide prevention, local people
      clearly link self-destruction with historical oppression, loss of the Inupiaq
      culture and current manifestations of these realities in alcoholism, abuse and
      neglect. This narrative typically focuses on young people and the Inupiaq
      community's current failure to lead them to a bright future. The article
      describes these understandings and offers suggestions to expand them in order to
      create new possibilities for community-based prevention and the promotion of
      wellness in circumpolar communities.

PMID- 16952417
TI  - Comparison of two types of dipsticks to measure vaginal pH in clinical practice.
AB  - OBJECTIVES: To assess the practical use of two dispsticks for measuring vaginal
      pH with a range 4-7 (Merck and Macherey Nagel in the diagnosis of vaginal
      infections. STUDY DESIGN: Routine gynaecological clinic in the General Hospital H
      Hart in Tienen and vulvo-vaginitis clinic in the University Hospital Gasthuisberg
      in Leuven, Belgium. After oral consent was obtained, 101 unselected consecutive
      women presenting for gynaecologic examination between 15 January 2004 and 15
      February 2004 were included in an observational study. Vaginal smears were taken
      from the upper vaginal wall for pH measurement and for fresh wet mount
      examination by phase contrast microscopy for diagnosing lactobacillary grades and
      presence of pathogens. The observed color change of two different pH strips were
      compared with the color scale provided by the company by a junior investigator
      who was not familiar with the technique, nor with the pathology of the patient.
      The difficulty of the measurement was scored semi-quantitatively by assessing the
      time and effort necessary to decide on the correct pH. RESULTS: Using the
      Macherey-Nagel method, the mean pH score was lower in women with normal flora and
      in women with vaginal infections than when the Merck method was used, but the
      difference was not significant. The pH became progressively more abnormal with
      increasing lactobacillary grades, a correlation that was similar for both tests.
      The reading of the pH sticks was significantly simpler and quicker with Macherey
      Nagel than with Merck. Although difficult readings with Merck strips were four
      times more frequent in the group of women with abnormal flora than in women with
      normal flora, this difference was not significant. CONCLUSION: (1) In both tests
      (Macherey-Nagel and Merck) the pH was more abnormal (higher) with increasing
      lactobacillary grades (declining number of lactobacillary morphotypes). (2) The
      Macherey-Nagel sticks are more user-friendly than Merck's.

PMID- 16952418
TI  - The validity of air and saline hysterosalpingo-contrast sonography in tubal
      patency investigation before insemination treatment.
AB  - OBJECTIVE: To compare the prognostic significance of tubal patency investigation
      by means of laparoscopy, hysterosalpingo-contrast sonography (HyCoSy) with air
      and saline as a contrast medium, and hysterosalpingography (HSG) in relation to
      the outcome of intrauterine insemination (IUI) treatment. STUDY DESIGN: A
      retrospective study of 559 consecutive women attending the university hospital
      infertility clinic for infertility treatment in 1996-2003. Tubal patency was
      evaluated by laparoscopy in 261 women, by HyCoSy in 217 and by HSG in 81 women
      before insemination treatment. Altogether, 1240 insemination cycles were
      evaluated and the results were compared in the three study groups. RESULTS: The
      clinical pregnancy rates per cycle were 14%, 18% and 18% in the laparoscopic,
      HyCoSy and HSG groups, with no statistically significant difference between the
      groups. The cumulative pregnancy rates (mean 2.3 cycles) were 30%, 41% and 38%,
      respectively, with a significant difference between the study groups. In cases of
      unilateral patency, cumulative pregnancy rates after two cycles were 18%
      (laparoscopy), 29% (HyCoSy) and 29% (HSG). The numbers of tubal pregnancies were
      similar in the subgroups. CONCLUSIONS: Hysterosalpingo-contrast sonography with
      air and saline as a contrast medium is a very cost-effective tubal investigation
      method as regards selection of subjects for insemination.

PMID- 16952419
TI  - A mesoscopic stochastic mechanism of cytosolic calcium oscillations.
AB  - Based on a model of intracellular calcium (Ca(2+)) oscillation with self
      modulation of inositol 1,4,5-trisphosphate signal, the mesoscopic stochastic
      differential equations for the intracellular Ca(2+) oscillations are
      theoretically derived by using the chemical Langevin equation method. The effects
      of the finite biochemical reaction molecule number on both simple and complex
      cytosolic Ca(2+) oscillations are numerically studied. In the case of simple
      intracellular Ca(2+) oscillation, it is found that, with the increase of molecule
      number, the coherence resonance or autonomous resonance phenomena can occur for
      some external stimulation parameter values. In the cases of complex cytosolic
      Ca(2+) oscillations, each extremum of concentration of cytosolic Ca(2+)
      oscillations corresponds to a peak in the histogram of Ca(2+) concentration, and
      the most probability appeared during the bursting plateau level for bursting, but
      at the largest minimum of Ca(2+) concentration for chaos. For quasi-periodicity,
      however, there are only two peaks in the histogram of Ca(2+) concentration, and
      the most probability is located at low concentration state.

PMID- 16952420
TI  - Effects of rapamycin on cell proliferation and phosphorylation of mTOR and
      p70(S6K) in HepG2 and HepG2 cells overexpressing constitutively active Akt/PKB.
AB  - Mammalian target of rapamycin (mTOR) is a serine-threonine kinase that plays an
      important role in the regulation of cell proliferation and protein synthesis
      through the activation of its downstream target ribosomal p70 S6 kinase
      (p70(S6K)). The levels of p-mTOR are regulated by the protein kinase B (Akt/PKB).
      Therefore, the effects of insulin and rapamycin (an inhibitor of mTOR) on the
      phosphorylation of mTOR (Ser 2448) and p70(S6K) (Thr 389) as well as on cell
      proliferation in parental HepG2 cells and HepG2 cells overexpressing
      constitutively active Akt/PKB (HepG2-CA-Akt/PKB) were studied. Insulin increased
      the levels of phosphorylated mTOR and p70(S6K) in both the cell lines. Rapamycin
      treatment partially decreased the phosphorylation of mTOR but completely
      abolished the phosphorylation of p70(S6K) in the absence as well as presence of
      insulin in both cell lines. The effect of insulin and rapamycin on the cell
      proliferation in both cell lines was further studied. In the presence of serum,
      parental HepG2 cells and HepG2-CA-Akt/PKB showed an increase in cell
      proliferation until 120 and 168 h respectively. Rapamycin inhibited cell
      proliferation under all experimental conditions more evident under serum deprived
      conditions. Parental HepG2 cells showed decline in the cell proliferation after
      48 h and the presence of insulin prolonged cell survival until 120 h and this
      effect were also inhibited by rapamycin under serum deprived conditions. On the
      contrary, HepG2-CA-Akt/PKB cells continued proliferation until 192 h. The effects
      of insulin on cell proliferation were more pronounced in parental HepG2 cells as
      compared to HepG2-CA-Akt/PKB cells. Long term effects of rapamcyin significantly
      decreased the levels of p-mTOR (Ser 2448) both in the presence and absence of
      insulin in these cells. A positive correlation between the levels of p-mTOR
      (Ser2448) and cell proliferation was observed (99% confidence interval,
      r(2)=0.525, p<0.0001). These results suggest that rapamycin causes a decline in
      the cell growth through the inhibition of mTOR.

PMID- 16952421
TI  - First report of a xylose-specific lectin with potent hemagglutinating,
      antiproliferative and anti-mitogenic activities from a wild ascomycete mushroom.
AB  - From fresh fruiting bodies of the wild ascomycete mushroom (Xylaria hypoxylon) a
      lectin with N-terminal sequence resemblance to a part of Aspergillus oryzae
      genome and only slight similarity to fungal immunomodulatory protein from the
      mushroom Flammulina velutipes was isolated. The protocol comprised extraction
      with water, precipitation from the aqueous extract using 80% saturated
      (NH(4))(2)SO(4), ion exchange chromatography on DEAE-cellulose and CM-cellulose,
      and then gel filtration by fast protein liquid chromatography on Superdex 75.
      Lectin activity was adsorbed on DEAE-cellulose and unadsorbed on CM-cellulose.
      The lectin appeared as a single band with a molecular mass of 14.4 kDa in sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and a single 28.8-kDa peak in
      gel filtration on Superdex 75. The lectin exhibited highly potent
      antiproliferative activity toward tumor cell lines, and exerted a potent anti
      mitogenic action on mouse splenocytes. The hemagglutinating activity of the
      lectin was inhibited by inulin and xylose. It was stable up to 35 degrees C. At
      40 degrees C its hemagglutinating activity was reduced by 50%, and it dwindled to
      12.5% of the original activity at 50 degrees C. The hemagglutinating activity was
      also sensitive to NaOH and HCl solutions. The hemagglutinating activity was
      unaffected by CaCl(2) and ZnCl(2), and was potentiated substantially in the
      presence of AlCl(3) and FeCl(3). The distinctive features of this lectin comprise
      a unique sugar specificity, and highly potent hemagglutinating, antiproliferative
      and anti-mitogenic activities. X. hypoxylon lectin differs in molecular mass, N
      terminal sequence and sugar specificity from previously reported ascomycete
      mushroom lectins.

PMID- 16952422
TI  - Mutation of Lys242 allows Delta3-Delta2-enoyl-CoA isomerase to acquire enoyl-CoA
      hydratase activity.
AB  - We report here a novel example of generating hydratase activity through site
      directed mutagenesis of a single residue Lys242 of rat liver mitochondrial Delta3
      Delta2-enoyl-CoA isomerase, which is one of the key enzymes involved in fatty
      acid oxidation and a member of the crotonase superfamily. Lys242 is at the C
      terminal of the enzyme, which is far from the active site in the crotonase
      superfamily and forms a salt bridge with Asp149. A variety of mutant expression
      plasmids were constructed, and it was observed that mutation of Lys242 to
      nonbasic residues allowed the mutants to have enoyl-CoA hydratase activity
      confirmed by HPLC analysis of the incubation mixture. Kinetic studies of these
      mutants were carried out for both isomerase and hydratase activities. Mutant
      K242C showed a k(cat) value of 1.0 s(-1) for hydration reaction. This activity
      constitutes about 10% of the total enzyme activity, and the remaining 90% is its
      natural isomerase activity. To the best of our knowledge, this is the first
      report on the generation of functional promiscuity through single amino acid
      mutation far from the active site. This may be a simple and efficient approach to
      designing a new enzyme based on an existing template. It could perhaps become a
      general methodology for facilitating an enzyme to acquire a type enzymatic
      activity that belongs to another member of the same superfamily, by interrupting
      a key structural element in order to introduce ambiguity, using site-directed
      mutagenesis.

PMID- 16952423
TI  - Effects of acute hypobaric hypoxia on the nitric oxide system of the rat cerebral
      cortex: Protective role of nitric oxide inhibitors.
AB  - Exposure to hypobaric hypoxia produces neuropsychological disorders. The brain
      nitrergic system was investigated following hypobaric hypoxia in the presence or
      absence of nitric oxide synthase (NOS) inhibitors. Adult rats were exposed to a
      simulated altitude of 8325 m (27,000 ft) for 7 h and killed after 0, 1, 3, 5, and
      10 days of recovery. In addition to normobaric controls, three experimental
      groups were studied: i) subjected to hypobaric hypoxia without inhibitors; ii)
      subjected to hypobaric hypoxia and treated with 7-nitroindazole; iii) subjected
      to hypobaric hypoxia and treated with N(omega)-nitro-l-arginine methyl ester (l
      NAME). Cerebral cortex was assayed by immunohistochemistry, Western blotting, and
      enzymatic assays. In animals subjected to hypobaric hypoxia without inhibitors,
      there was an increase in neuronal nitric oxide synthase (nNOS) immunoreactivity
      and Ca(2+)-dependent NOS activity from 0 to 1 days of reoxygenation. In these
      animals, inducible nitric oxide synthase (iNOS) expression and Ca(2+)-independent
      activity were undetectable, but nitrotyrosine immunoreactivity was found in some
      neurons. Administration of either inhibitor prevented the increase in nNOS
      immunoreactivity and enzymatic activity provoked by hypobaric hypoxia.
      Concomitantly, nitrotyrosine immunoreactivity decreased progressively. In
      conclusion, activation of the nitrergic system constitutes a cortical response to
      hypobaric hypoxia and the administration of NOS inhibitors could provide new
      therapeutic avenues to prevent and/or treat the symptoms produced by hypobaric
      hypoxia.

PMID- 16952424
TI  - Endogenous alpha2-adrenergic receptor-mediated neuroprotection after severe
      hypoxia in preterm fetal sheep.
AB  - Central alpha-adrenergic receptor activity is important for fetal adaptation to
      hypoxia before birth. It is unclear whether it is also important during recovery.
      We therefore tested the hypothesis that an infusion of the specific alpha(2)
      adrenergic receptor antagonist idazoxan (1 mg/kg/h i.v.) from 15 min to 4 h after
      profound hypoxia induced by 25 min umbilical cord occlusion in fetal sheep at 70%
      of gestation (equivalent to the 28-32 weeks in humans) would increase neural
      injury. After 3 days' recovery, idazoxan infusion was associated with a
      significant increase in neuronal loss in the hippocampus (P<0.05), expression of
      cleaved caspase-3 (P<0.05), and numbers of activated microglia (P<0.05). There
      was no significant effect on other neuronal regions or on loss of O4-positive
      premyelinating oligodendrocytes in the subcortical white matter. Idazoxan was
      associated with an increase in evolving epileptiform electroencephalographic
      (EEG) transient activity after occlusion (difference at peak 2.5+/-1.0 vs. 11.7+/
      4.7 counts/min, P<0.05) and significantly reduced average spectral edge
      frequency, but not EEG intensity, from 54 until 72 h after occlusion (P<0.05).
      Hippocampal neuronal loss was correlated with total numbers of epileptiform
      transients during idazoxan infusion (P<0.01; r(2)=0.7). In conclusion, endogenous
      inhibitory alpha(2)-adrenergic receptor activation after severe hypoxia appears
      to significantly limit evolving hippocampal damage in the immature brain.

PMID- 16952425
TI  - N-methyl-D-aspartate receptors in the medial septal area have a role in spatial
      and emotional learning in the rat.
AB  - Cholinergic and GABAergic neurons in the medial septal/vertical limb of the
      diagonal band of Broca (MS/vDB) area project to the hippocampus and constitute
      the septohippocampal pathway, which has been implicated in learning and memory.
      There is also evidence for extrinsic and intrinsic glutamatergic neurons in the
      MS/vDB, which by regulating septohippocampal neurons can influence hippocampal
      functions. The potential role of glutamatergic N-methyl-D-aspartate (NMDA)
      receptors within the MS/vDB for spatial and emotional learning was studied using
      the water maze and step-through passive avoidance (PA) tasks, which are both
      hippocampal-dependent. Blockade of septal NMDA receptors by infusion of the
      competitive NMDA receptor antagonist D-(-)-2-amino-5-phosphonopentanoic acid (D
      AP5) (0.3-5 microg/rat), infused 15 min prior to training, impaired spatial
      learning and memory at the 5 microg dose of D-AP5, while doses of 0.3 and 1
      microg per rat had no effect. The impairment in spatial learning appears not to
      be caused by sensorimotor or motivational disturbances, or anxiogenic-like
      behavior. Thus, d-AP5-treated rats were not impaired in swim performance or
      visuospatial abilities and spent more time in the open arms of the elevated plus
      maze. In the PA task, intraseptal D-AP5 infused 15 min before training impaired
      retention as examined 24 h after training. This impairment was observed already
      at the 0.3 microg dose, suggesting that NMDA receptors within the MS/vDB may be
      more important for emotional than spatial memory. In summary, the present data
      indicate that changes in septal glutamate transmission and NMDA receptor activity
      can influence activity-dependent synaptic plasticity in the hippocampus and
      thereby learning and memory.

PMID- 16952426
TI  - Correspondence in collateral and self-reports on alcohol consumption: a within
      family analysis.
AB  - The present study tests the degree to which parents and children correspond in
      their reports on each others quantity and frequency of alcohol consumption.
      Furthermore, the degree of inaccurate estimation by parents might be related to
      inappropriate parenting. Particularly, parents who have little control over and
      knowledge of their offspring's activities and whereabouts might underestimate
      adolescent alcohol consumption. A full family design was employed in which both
      parents and two adolescents were included. A total of 428 Dutch families
      participated and filled in questionnaires at home in the presence of a trained
      interviewer on frequency and quantity of drinking. Findings showed that parents
      as well as children underestimate alcohol consumption of each other, in
      particular concerning the quantity of drinking. It appears that parents are
      better able to accurately estimate when their child is not drinking than when
      their child is drinking. Children on the other hand are better able to predict
      frequency and quantity of parental drinking, but not parental heavy drinking.
      Finally, parental underestimations of adolescent drinking are indeed related to
      lack of parental knowledge and control. However, this was primarily found among
      mothers. In conclusion, survey studies using collateral reports on parental and
      adolescent drinking should acknowledge the fact that in most cases family members
      underestimate alcohol consumption.

PMID- 16952427
TI  - Time-place learning in individually reared angelfish, but not in pearl cichlid.
AB  - Time-place learning based on food association was investigated in the cichlids
      angelfish (Pterophyllum scalare) and pearl cichlid (Geophagus brasiliensis)
      reared in isolation, therefore eliminating social influence on foraging. During a
      30-day period, food was placed in one side of the aquarium (containing three
      compartments) in the morning and in the opposite side in the afternoon. Learning
      was inferred by the number of correct side choices of all fish in each day of
      test (15th and 30th). During the test day fish were not fed. The angelfish
      learned to switch sides at the correct day period in order to get food,
      suggesting this species has time-place learning ability when individually reared.
      On the other hand, the same was not observed for pearl cichlid.

PMID- 16952428
TI  - Characterization of the human PRIP-1 gene structure and transcriptional
      regulation.
AB  - The PRIP [phospholipase C related, but catalytically inactive protein] family has
      been isolated as a novel inositol 1,4,5-trisphosphate binding protein with a
      domain organization similar to phospholipase C-delta but lacking the enzyme
      activity, comprising PRIP-1 and PRIP-2. The PRIP-1 gene is expressed
      predominantly in the brain, while PRIP-2 exhibits a relatively ubiquitous
      expression in rats and mice. We also found that PRIP-1 plays an important role in
      type A receptor signaling for gamma-aminobutyric acid in the brain. In this
      study, we investigated PRIP-1 gene structure and the possible mechanisms involved
      in the expression. The tissue distribution pattern of PRIP gene expression in
      humans was similar to that in rodents. 5'RACE (rapid amplification of cDNA ends)
      analysis using PRIP-1 gene specific primers with human brain mRNA revealed the
      presence of three new exons, indicating that the PRIP-1 gene is organized into 8
      exons intervened by 7 introns. Although three transcripts resulting from the
      alternative splicing of exon 2 and/or 3 were detected, a transcript lacking exons
      2 and 3 was predominantly expressed in humans, suggesting that the translation
      start codon of human PRIP-1 exists in exon 1. To characterize the human PRIP-1
      promoter, transient luciferase assay was carried out with luciferase constructs
      including various lengths of the 5' flanking region of the PRIP-1 gene. The
      results indicated that the positive regulatory region is located -237 to -108 bp
      upstream from the transcription start site. Gel shift assay revealed the specific
      binding of some nuclear proteins to this region, suggesting that the existence of
      transcription factors contributes to the positive regulation of PRIP-1 gene
      expression. Mutation analyses revealed that the binding of a transcription
      factor, MAZ to the regulatory site leads to the promoter activity, indicating
      that MAZ is involved in the expression regulation of the human PRIP-1 gene.

PMID- 16952429
TI  - In response to: "Commentary on: Mark Benecke and Larry Barksdale, Distinction of
      bloodstain patterns from fly artifacts: Forensic Science International 137 (2003)
      152-159" [Forensic Sci. Int. 149 (2/3) (2005) 293-294].

PMID- 16952430
TI  - The influence of Er. YAG laser application in fenestration to the inner ear.
AB  - OBJECTIVE: Erbium (Er.) YAG laser may be usable for middle ear surgery because of
      its ability to ablate bony tissue. We investigated the inner ear damage caused by
      the fenestration to the inner ear with Er. YAG laser. DESIGN: We investigated the
      influence of Er. YAG laser on the inner ear using electrophysiological technique.
      RESULTS: Several cases had a decrease in endocochlear potential (EP) and cochlear
      microphonics (CM) after the fenestration to the inner ear. CONCLUSIONS: Er. YAG
      laser is safe if it is used for the small and superficial fenestration to the
      stapes footplate. However, a few extra pulses after fenestration are dangerous.

PMID- 16952431
TI  - Successful treatment of nasal septum hemangioma with the Harmonic Scalpel: a case
      report.
AB  - Hemangioma of the nasal septum, known as "bleeding polyp," is an occasional
      lesion in adults. We report two cases of bleeding polyps, that were successfully
      treated by surgery using the Harmonic Scalpel (HS). Two women (aged 58 and 67
      years) presented with unilateral nasal hemangioma, which was revealed by
      unilateral epistaxis. Both the women were treated by surgical excision using the
      HS under general and local anesthesia, respectively. Treatment involves surgical
      excision of the tumor including the mucosa and the underlying perichondrium. HS
      is an effective tool for the excision of bleeding polyps with less bleeding and
      less tissue injury.

PMID- 16952432
TI  - The influence of inflation rate on the hematologic and hemodynamic effects of
      intermittent pneumatic calf compression for deep vein thrombosis prophylaxis.
AB  - OBJECTIVE: The study was conducted to determine whether the different inflation
      rates of intermittent pneumatic compression systems used in deep vein thrombosis
      prophylaxis influence their hematologic and hemodynamic effects. METHODS: A
      rapidly inflating intermittent calf compression system and a more gently
      inflating equivalent were applied to 20 healthy male volunteers for 2 hours each.
      Venous blood samples were taken for analysis of blood coagulation and
      fibrinolytic potential. Blood flow velocity was measured in the femoral vein with
      Doppler ultrasound. RESULTS: Tissue factor pathway inhibitor significantly
      increased after the 2 hours of compression for both pumps (78.0 to 85.0 ng/mL
      rapid, P = .004; 76.5 to 78.0 ng/mL gentle, P = .5), as did plasminogen activator
      activity (0.85 to 1.05 IU/mL rapid, P = .006; 0.85 to 1.5 IU/mL gentle, P = 0.5).
      Plasminogen activator inhibitor 1 activity was reduced, although only approaching
      significance for the gentle system (16.5 to 14.3 AU/mL, P = .06). A D-dimer test
      for global fibrinolysis showed significant increases for the gently inflating
      system (97 to 411 ng/mL P < .001) but not for the rapidly inflating system (276
      to 350 ng/mL P = .9). The rapidly inflating system produced significantly higher
      venous peak velocities and augmentations as expected. CONCLUSIONS: Although the
      data confirm that both types of intermittent compression suppress procoagulant
      activation, rapid inflation clearly produced no extra benefit in increasing
      global fibrinolysis, and may be less hematologically effective.

PMID- 16952433
TI  - Histologic evaluation of radiofrequency ablation in renal cancer.
AB  - AIM: To report on the histologic evaluation of renal tumors after intraoperative
      radiofrequency ablation (RFA) performed immediately before surgical nephrectomy.
      MATERIALS AND METHODS: Ten patients with renal tumors were studied. All tumors
      were confirmed to be renal cell carcinoma before radio frequency ablation
      treatment. All specimens were stained with hematoxylin and eosin and nicotinamide
      adenine dinucleotide (NADH). RESULTS: Mean tumor size was 29 mm (range 14 to 48
      mm). Of the 10 tumors 5 were completely devitalized with a treatment margin
      ranged from 1 to 20mm. One tumor needed two treatment sessions. No complication
      related to radiofrequency treatment was recorded. CONCLUSIONS: Our data indicate
      that RFA can completely destroy renal tumors. However, in our study, complete
      tumor cell death was obtained only in 50% of cases. More studies are needed to
      ensure that is technique is an effective and reproducible treatment.

PMID- 16952435
TI  - Innovative nanotechnologies for the delivery of oligonucleotides and siRNA.
AB  - One way to reach intracellular therapeutic targets in cells consists in the use
      of short nucleic acids which will bind specifically to on targets thanks to
      either Watson-Crick base pairing or protein nucleic acids recognition rules.
      Among these short nucleic acids an important class of therapeutic agents is
      antisense oligonucleotides and siRNAs. However, the major problem of nucleic
      acids is their poor stability in biological media. One method, among others, to
      solve the stability problem is the use of colloidal carriers such as
      nanoparticles. Nanoparticles have already been applied with success to in vitro
      drug delivery to particular types of cells and in vivo in several experimental
      models. Many membrane and intracellular processes deal with nanosized structure
      (typically 100 nm) which are processed further through the recognition sites of
      receptors and enzymes. Thus non-viral nanoparticles are interesting candidates to
      present biochemical molecules such as nucleic acids and proteins to cells as well
      as to protect them in vivo during delivery. This review focuses on the recent
      developments in the design of nanotechnologies to improve the delivery of
      antisense oligonucleotides and siRNAs.

PMID- 16952434
TI  - Neoadjuvant chemotherapy and radical surgery compared to radical surgery alone in
      bulky stage IB-IIA cervical cancer.
AB  - AIM: The aim of this study was evaluation of the efficacy of neoadjuvant
      chemotherapy (NACT) and radical hysterectomy on long-term survival in stage IB
      IIA locally advanced cervical cancer as compared with radical surgery alone.
      METHODS: We reviewed all patients with cervical cancer stage IB-IIA who were
      treated with two treatment modalities, i.e. NACT followed by radical hysterectomy
      and lymphadenectomy, and radical hysterectomy alone between March 1996 and March
      2004. There were 22 patients in the NACT group (group 1) and 160 patients in the
      immediate radical surgery group (group 2). All patients in group 1 were followed
      for more than 108months, and long-term survival and factors affecting recurrence
      were evaluated. RESULTS: Nineteen patients in the NACT arm underwent radical
      surgery. Pelvic lymph node metastasis was found in 8 patients in this group and
      in 36 in the radical surgery group. Eighteen patients in the NACT group and 96
      patients in the radical surgery group were scheduled for adjuvant postoperative
      chemoradiation. During the 9-year follow-up, recurrence rate was 47.1% and 30.2%
      in NACT and control groups, respectively. In the NACT group lymph node metastasis
      was a significant independent risk factor for recurrence. Overall survival in the
      NACT arm was not statistically significantly lower than the control arm (p=0.06).
      CONCLUSION: NACT did not improve long-term overall survival of bulky early-stage
      cervical cancer patients compared to primary radical surgery.

PMID- 16952436
TI  - Flavanone metabolism in healthy and tumor-bearing rats.
AB  - Flavanones, the main polyphenols of citrus fruits, are thought to contribute to
      the protective effects of these fruits against cardiovascular diseases and
      cancer. The metabolism of naringin (naringenin 7-O-neohesperidoside) is studied
      here in healthy (sham-operated, ShO) and tumor-bearing (TuB) rats. The tumor was
      induced by implanting Yoshida's sarcoma in hindlimb. Both groups received for 7
      days a semi-synthetic diet containing 0.5% naringin in per feeding conditions.
      Flavanones were analyzed in plasma, liver, kidney and urine by tandem mass
      spectrometry. Naringenin conjugates (essentially glucuronides) accounted for up
      to 98% of the total flavanones in plasma. Low amounts of hesperetin (4'-O-methyl
      naringenine) and isosakuranetin (3'-hydroxy-4'-O-methylnaringenin) were also
      detected in all biological samples and accounted for 2% of the total flavanones
      in plasma. They were largely present as aglycones. The in vivo hydroxylation of
      flavanones is described here for the first time. Total concentrations of
      naringenin metabolites reached 17.3+/-2.7 microM in plasma 6 hours after the
      beginning of the meal in healthy rats and only 10.6+/-1.3 microM in TuB rats. The
      nature of metabolites was similar in both healthy and TuB rats and in plasma,
      tissues and urine. The lower concentration of flavanones in the TuB rats suggests
      that disease and more particularly cancer, may affect the bioavailability of
      flavonoids.

PMID- 16952437
TI  - Identification of a newly spliced exon in the mouse Ilf3 gene generating two long
      and short isoforms of Ilf3 and NF90.
AB  - The mammalian IlF3 and NF90 proteins, involved in several cellular functions,
      have common N-terminal and central sequences and specific C-terminal regions.
      These proteins exhibit a large heterogeneity generated by posttranscriptional and
      posttranslational modifications. Part of their polymorphism is due to the
      alternative splicing of exon 3 located just downstream of the translation
      initiation codon. This 39-nucleotide-long exon, not described so far, codes for
      an N-terminal sequence of 13 residues (ALYHHHFITRRRR) also present in rat and
      human IlF3 or NF90. Four mRNAs are expressed in mouse brain, two for Ilf3 and two
      for NF90, differing in their 3' sequence to generate the specific Ilf3 and NF90 C
      terminal domains and in the presence or the absence of exon 3 to generate long
      and short isoforms of both proteins. By RT-PCR, no other variants were found.
      Combining our results and GenBank sequences, we determined the exon-intron
      organization of the entire mouse Ilf3 gene divided into 22 exons.

PMID- 16952438
TI  - Toxicity of di(2-ethylhexyl)phthalate (DEHP) and di(2-ethylhexyl)adipate (DEHA)
      under conditions of renal dysfunction induced with folic acid in rats:
      enhancement of male reproductive toxicity of DEHP is associated with an increase
      of the mono-derivative.
AB  - F344 male rats were given five consecutive weekly subcutaneous injections of
      folic acid for induction of chronic renal dysfunction and then di(2
      ethylhexyl)phthalate (DEHP) or di(2-ethylhexyl)adipate (DEHA) in the diet at a
      concentration of 0, 6000 or 25,000 ppm for 4 weeks in order to investigate
      whether male reproductive toxicity of the two chemicals might be enhanced under
      conditions of renal disease. Control animals also received DEHP or DEHA in the
      same manner but without folic acid pretreatment. Decreased testicular weights,
      seminiferous atrophy with vacuolization of sertoli cells and diminished sperm
      counts were more prominent in rats given folic acid and then 25,000 ppm DEHP as
      compared to those exposed to DEHP alone. No such reproductive toxicity was
      evident in rats given 6000 ppm DEHP or either dose of DEHA. An increased
      concentration of the mono-derivative of DEHP (mono(2-ethylhexyl)phthalate, MEHP)
      in the blood, testis and urine was considered relevant to the enhanced
      reproductive toxicity observed with DEHP.

PMID- 16952439
TI  - Expression of apoptosis-associated molecules in the fetoplacental unit of
      cyclophosphamide-treated mice.
AB  - The mechanisms underlying the teratogen-induced apoptotic process leading to
      anomaly formation are not as yet understood. Therefore, we tried to evaluate
      possible changes in the expression of molecules regulating the apoptotic process
      induced in the embryo and placenta by exposure to cyclophosphamide (CP). Exposure
      to CP resulted in clear growth retardation that was accompanied by a time
      dependent increase in cellular damage and an appearance of apoptotic cells in the
      embryonic brain and limbs as well as a decrease in cell proliferation. Western
      blot analysis demonstrated an increase in the level of Bax and a decrease in the
      expression of the p65 subunit of NF-kappaB and IkappaB alpha in the embryo and
      placenta. Immunohistochemical analysis localized cells expressing those molecules
      to the areas that exhibited CP-induced cellular damage, while in the placenta
      they were revealed mainly in the luminal and glandular epithelium. Our results
      suggest a possible involvement of Bax, p65 and IkappaB alpha in the response of
      the embryo and the placenta to teratogenic insults.

PMID- 16952440
TI  - Acoustic voice analysis of prelingually deaf adults before and after cochlear
      implantation.
AB  - It is widely accepted that many severe to profoundly deaf adults have benefited
      from cochlear implants (CIs). However, limited research has been conducted to
      investigate changes in voice and speech of prelingually deaf adults who receive
      CIs, a population well known for presenting with a variety of voice and speech
      abnormalities. The purpose of this study was to use acoustic analysis to explore
      changes in voice and speech for three prelingually deaf males pre- and
      postimplantation over 6 months. The following measurements, some measured in
      varying contexts, were obtained: fundamental frequency (F0), jitter, shimmer,
      noise-to-harmonic ratio, voice turbulence index, soft phonation index, amplitude-
      and F0-variation, F0-range, speech rate, nasalance, and vowel production.
      Characteristics of vowel production were measured by determining the first
      formant (F1) and second formant (F2) of vowels in various contexts, magnitude of
      F2-variation, and rate of F2-variation. Perceptual measurements of pitch, pitch
      variability, loudness variability, speech rate, and intonation were obtained for
      comparison. Results are reported using descriptive statistics. The results showed
      patterns of change for some of the parameters while there was considerable
      variation across the subjects. All participants demonstrated a decrease in F0 in
      at least one context and demonstrated a change in nasalance toward the norm as
      compared to their normal hearing control. The two participants who were oral
      language communicators were judged to produce vowels with an average of 97.2%
      accuracy and the sign-language user demonstrated low percent accuracy for vowel
      production.

PMID- 16952441
TI  - Stochastic models of decisions about motion direction: behavior and physiology.
AB  - Roitman and Shadlen [Roitman J. D., & Shadlen M. N. (2002). Response of neurons
      in the lateral intraparietal area during a combined visual discrimination
      reaction time task. Journal of Neuroscience, 22, 9475-9489] have published a non
      human primate study on visual decision making. They collected both behavioral and
      neurophysiological data and provided evidence that the data are qualitatively
      consistent with a mechanism based on accumulating sensory evidence up to a
      decision threshold. I have previously demonstrated that a time-variant diffusion
      model can account quite well quantitatively for both the behavioral and the
      neural data. In this manuscript I discuss how well the data constrains different
      components and parameters of the computational process. I also discuss the
      biological plausibility of the model parameters. I will demonstrate that a
      relatively large class of models, both with and without temporal integration and
      both stationary and time-variant could account for the behavioral data. Both the
      single cell recordings from the parietal cortex and previously published data
      from the extrastriate visual cortex provide additional constraints. Overall, the
      data favor a diffusion model with time-variant gain and leaky integrators. The
      integration time constant, however, turns out not to be well-constrained by the
      data.

PMID- 16952442
TI  - Behavioral inhibition and prefrontal cortex in decision-making.
AB  - Every day we make innumerable decisions; some require no effort at all whereas
      others require considerable deliberation and weighing of various options. Despite
      the importance of decision-making in our lives and increased research interest,
      the specific neural mechanisms underlying decision-making remain unclear. We
      propose that the brain has at least two cortical pathways that independently
      generate a decision about appropriate behavior in given circumstances. These two
      pathways are extensions of the dorsal and ventral streams of the visual
      processing pathways. The parieto-premotor (extended dorsal) pathway makes
      decisions about motor actions in a largely autonomous and automatic fashion
      whereas the temporo-ventrolateral prefrontal (extended ventral) pathway is
      involved primarily in deliberate decisions and inhibitory control over behavior
      through the inhibitory function of the ventrolateral prefrontal cortex.

PMID- 16952443
TI  - Cardiac autonomic dysfunctions in chronic refractory epilepsy.
AB  - BACKGROUND: Sudden unexplained death is an important cause of mortality in
      patients with epilepsy and cause for this is not fully understood. One of the
      explanations is autonomic dysfunction (AD). Studies of AD in chronic refractory
      epilepsy are very few in the literature. AIM: To evaluate cardiovascular
      autonomic functions in chronic refractory epilepsy patients. METHODS AND
      MATERIALS: Seventy-three patients (31.5+/-9.8 years, M:F::45:28) with chronic
      intractable epilepsy attending the "refractory epilepsy clinic" at a tertiary
      referral center (National Institute of Mental Health and Neuro Sciences
      (NIMHANS), Bangalore, India) were enrolled. Age and gender matched healthy
      subjects were recruited as controls. Heart rate (HR) and blood pressure (BP) at
      rest and HR response after deep breathing, Valsalva maneuver, postural change and
      BP response to postural change and isometric work were recorded. AD was graded as
      early if one of HR or BP, definite if two or more HR and severe if two or more HR
      with BP based tests were detected to be abnormal. RESULTS: The mean age at onset
      and duration of epilepsy was 12.4+/-8.5 years and 19.02+/-9.07 years,
      respectively. Twenty-three (31.5%) patients of refractory epilepsy had early
      involvement while 25 patients (primary generalized: 8, partial: 17) had Definite
      AD, and 16 (primary generalized: 4, partial: 12) had severe autonomic
      dysfunction. ANCOVA results showed expiration-inspiration, standing
      maximum:minimum ratio, standing 2 min systolic and isometric diastolic BP of the
      dysfunction group significantly differ compared to the control group. Patients
      with longer duration of epilepsy (23.2 years) had more severe dysfunction (p <
      0.05) than patients with relatively shorter duration (17.5 years) of epilepsy.
      Antiepileptic drugs (AED) used did not show any significant role on autonomic
      functions in this study. CONCLUSION: This is the first study from India to
      evaluate autonomic functions in refractory epilepsy patients. Autonomic
      dysfunction was noted in 56.3% of patients. Anticonvulsants used were not
      associated with AD. Longitudinal controlled studies with 'newly diagnosed'
      epilepsy patients will enhance further understanding about the role of autonomic
      system in epilepsy.

PMID- 16952444
TI  - A comparative study of granzyme B expression in keratoacanthoma and squamous cell
      carcinoma.

PMID- 16952445
TI  - Prefrontal dysfunction in schizophrenia controlling for COMT Val158Met genotype
      and working memory performance.
AB  - Earlier studies with functional imaging in schizophrenia have demonstrated
      dysfunction of the dorsolateral prefrontal cortex during working memory.
      Controlling for behavioral performance and for catechol-O-methyltransferase
      (COMT) Val158Met genotype, we here demonstrate in a functional magnetic resonance
      imaging paradigm that patients recruit greater neuronal resources in prefrontal
      cortex during working memory, suggesting that this phenotype is a core functional
      trait of the disease. We also replicated earlier findings that the Val allele of
      the COMT polymorphism is associated with greater engagement of the prefrontal
      cortex.

PMID- 16952446
TI  - Orbitofrontal correlates of aggression and impulsivity in psychiatric patients.
AB  - The association between orbital frontal cortex (OFC) volume and aggression and
      impulsivity was investigated among a heterogeneous group of non-psychotic
      psychiatric clients. Fifteen non-psychotic subjects from two different
      psychiatric clinics (New England Medical Center and Lemuel Shattuck Hospital)
      with a variety of diagnoses were sequentially referred for magnetic resonance
      imaging (MRI) for clinical purposes. This convenience sample, clinically stable
      at the time of evaluation, received a standardized psychiatric diagnostic
      interview, aggression and impulsivity psychometrics (Barratt Impulsivity,
      Lifetime History of Aggression, and Buss-Perry Aggression scales), and an MRI
      protocol with image analysis. OFC gray matter volume, total as well as left and
      right, was significantly and positively associated with motor impulsivity. OFC
      asymmetry was associated with aggression, though total, left, and right OFC
      volume measurements were not. For subjects without affective disorder, there was
      a strong and positive association of the OFC to motor and no-planning subscales
      of the Barratt Impulsivity Scale. For subjects with affective disorder, there was
      a strong association of OFC asymmetry to both of the aggression psychometrics.
      Consistent with expectation, results are suggestive of OFC involvement in the
      neural circuitry of impulsivity and aggression. The findings suggest a
      dissociation of the role of the OFC in relation to aggression and impulsivity,
      such that the OFC may play a part in the regulation of aggressive behavior and a
      generative role in impulsive behavior.

PMID- 16952447
TI  - A morphometric magnetic resonance method for measuring cranial, facial and brain
      characteristics for application to schizophrenia: part 1.
AB  - Serious psychopathology in adulthood may be associated with disturbed foetal
      brain development, which potentially shows lingering "fossil marks" in the
      cranial and facial regions. Several methods exist for assessing external
      craniofacial and internal brain distances but, to our knowledge, no method yet
      provides simultaneous measurement of cranial, facial and brain dimensions in live
      subjects. In this article we describe a method to identify landmarks on magnetic
      resonance images (MRI) for simultaneous measurement of cranial, facial and brain
      characteristics potentially associated with psychosis. To test the method itself,
      30 patients with chronic schizophrenia and 31 healthy comparison subjects, mean
      age 41 years, were randomly selected from a larger cohort recruited at the
      Karolinska Hospital, Sweden. Participants were investigated with MRI, and 60
      landmarks in the cranial, facial and brain regions were identified in the images.
      An independent anthropometric examination measured external craniofacial
      characteristics for study in relation to measurements produced through MRI. High
      inter-scorer and re-test reliabilities were obtained for two independent scorers
      of the landmarks in the MR images. Measurements of potentially comparable
      craniofacial distances showed high alignment with an established anthropometric
      method. This new method can provide simultaneous investigation of multiple
      aspects of cranial, facial and brain morphology in MR images originally collected
      for other purposes. In a second article we will use this method to compare 3D
      craniofacial measurements and shape between schizophrenia patients and healthy
      controls.

PMID- 16952448
TI  - Dopamine transporter binding in depressed patients with anhedonia.
AB  - Central dopaminergic dysfunction has been widely proposed as a common
      neurobiological correlate of the psychopathological expression of anhedonia. The
      dopamine transporter (DAT) is a predominantly presynaptic receptor that may play
      a critical role in the pathophysiology of dopaminergic transmission. The aim of
      our study was to evaluate DAT binding in a population of depressed patients with
      anhedonia. Single photon emission computed tomography (SPECT) with the
      radiotracer DATSCAN was used to evaluate DAT binding in 11 depressed patients
      with anhedonia and 9 healthy comparison subjects. Compared with healthy subjects,
      patients showed significantly lower DAT binding. No significant correlation was
      found between DAT binding ratios and scores on administered psychometric tests.
      These findings suggest an alteration in DAT density in depressed patients with
      anhedonia that may be a primary susceptibility factor or a secondary phenomenon
      to reduced dopamine concentration in the synaptic cleft.

PMID- 16952450
TI  - Electrostatic characterisation of inhaled powders: effect of contact surface and
      relative humidity.
AB  - Electrostatic charge accumulation on drug and excipient powders arising from
      interparticulate collisions or contacts between particles and other solid
      surfaces often leads to agglomeration and adhesion problems during the
      manufacture and use of dry powder inhaler (DPI) formulations. The aim of this
      work was to investigate the role of triboelectrification in particle interactions
      between micronised drug (salbutamol sulphate or ipratropium bromide monohydrate)
      and excipient (alpha-lactose monohydrate, 63-90 microm) during mixing in
      cylindrical vessels constructed from stainless steel, polypropylene and acetal
      under selected relative humidity (rh) conditions (0-86%). The charge was found to
      depend on both the nature of the powders and the mixing vessel surface. In
      addition, coating the vessels with drug or excipient removed the influence of the
      vessel material on charge generation, thus providing a technique to investigate
      interactions between the drug and excipient substances. A triboelectric series of
      all materials used, placed ipratropium at the positive end and polypropylene at
      the negative end. Micronised drug profoundly altered the charging properties of
      lactose in drug (1.46%, w/w)/lactose DPI formulations. An increase in rh in the
      range 0-86% produced a corresponding decrease in charge and adhesion values for
      each drug, lactose and DPI formulation during triboelectrification with each
      mixing vessel surface. The results provide increased knowledge of the role of
      electrostatics in DPI technology.

PMID- 16952451
TI  - In vitro assessment of transferrin-conjugated liposomes as drug delivery systems
      for inhalation therapy of lung cancer.
AB  - Most human tumours over-express receptors for growth factors and peptide
      hormones, which are being increasingly studied as a means to selectively deliver
      cytotoxic agents. An example being the transferrin receptor (TfR, CD71). Here, we
      studied expression levels and location of TfR in different lung epithelial cell
      types (i.e., bronchial and alveolar epithelial cells) by flow-cytometry and
      confocal laser scanning microscopy (CLSM). Furthermore, we assessed uptake levels
      and cytotoxicity of transferrin (Tf)-conjugated liposomes in vitro. TfR was found
      to be expressed at a significantly higher level in bronchial epithelial cells
      compared with their alveolar counterparts. Cells of cancerous origin (i.e., A549
      cell line) showed a higher TfR expression level than healthy alveolar epithelial
      type II cells in primary culture. CLSM revealed TfR to be located primarily at
      the basolateral aspect of cells, with the exception of cells undergoing mitotic
      proliferation, which also showed TfR at their apical membranes, due to their loss
      of cell polarity. Higher expression levels of TfR correlated well with enhanced
      uptake of Tf-liposomes and increased levels of cytotoxicity. Liposome uptake was
      temperature-dependent and inhibitable by excess free Tf. Tf-conjugated liposomes
      appear as good candidates for an approach to deliver cytostatic drugs to sites of
      lung cancer by inhalation.

PMID- 16952452
TI  - Insulin encapsulation in reinforced alginate microspheres prepared by internal
      gelation.
AB  - Insulin-loaded alginate microspheres prepared by emulsification/internal gelation
      were reinforced by blending with polyanionic additive polymers and/or chitosan
      coating in order to increase the protection of insulin at simulated gastric pH
      and obtain a sustained release at simulated intestinal pH. Polyanionic additive
      polymers blended with alginate were cellulose acetate phtalate (CAP), Eudragit
      L100 (EL100), sodium carboxymethylcellulose (CMC), polyphosphate (PP), dextran
      sulfate (DS) and cellulose sulfate (CS). Chitosan-coating was applied by using a
      one-stage procedure. The influence of additive polymers and chitosan-coating on
      the size distribution of microspheres, encapsulation efficiency and release
      profile of insulin in simulated gastrointestinal pH conditions was studied. The
      mean diameter of blended microspheres ranged from 65 to 106 microm and
      encapsulation efficiency of insulin varied from 14 to 100%, reaching a maximum
      value when CS and DS were incorporated in the alginate matrix. Insulin release,
      at pH 1.2, was almost prevented by the incorporation of PP, DS and CS. When
      uncoated microspheres were transferred to pH 6.8, a fast dissolution occurred,
      independently of the additive polymer blended with alginate, and insulin was
      completely released. Increasing the additive polymer concentration in the
      alginate matrix and/or chitosan-coating the blended alginate microspheres did not
      promote a sustained release of insulin from microspheres at pH 6.8.

PMID- 16952453
TI  - SOD1 gene mutations in Italian patients with Sporadic Amyotrophic Lateral
      Sclerosis (ALS).
AB  - Mutations in the SOD1 gene exons and exon/intron boundaries were searched in 66
      sporadic and 4 familial Italian ALS cases consecutively referred to our centre
      from different Italian regions. A mutation was found in three sporadic cases
      (4.5%): a new nonsense mutation in exon 5 (K136X) in a patient with a rapid and
      severe disease course and two previously described missense nucleotide
      substitutions (N65S and A95T) in two patients with a mild disease course.
      Comparison of the clinical characteristics with previously reported patients
      carrying the same or similar mutations showed a remarkable genotype-phenotype
      correlation. No association was found with intronic sequence variations by
      comparing their frequency in the patients and in 181 matched controls.

PMID- 16952454
TI  - Imprint cytology of needle core-biopsy specimens of breast lesions: is it a
      useful adjunt to rapid assessment breast clinics?
AB  - This study aimed at assessing the practicability of imprint cytology (IC) of core
      biopsy (CB) specimens in order to achieve one-stop diagnosis of breast lesions.
      In total, 199 symptomatic patients underwent free-hand CB of the suspected breast
      lesions. The slides were stained by Diff-QuikO and reported independently of
      histological reporting. For practical reasons cytology specimens were graded as
      follows: C1=inadequate, as less than 4 groups of epithelial cells were seen,
      C2=benign, C3=probably benign, C4=probably malignant and C5=positive for
      malignancy. The results of IC were correlated with CB histology. Absolute
      sensitivity of the IC was 85.0% and complete sensitivity was 89.2% when
      correlated with CB. Specificity (biopsy cases only) of IC was 53.1% while full
      specificity was 53.1%. Positive predictive value of C5 was 99.3%, C4 55.6 % and
      C3 was 100%. Overall suspicious rate was 5.5%. It was concluded that IC is a
      reliable way of diagnosing symptomatic breast lesions in one-stop breast clinic
      and retains the advantage of pre-operative availability of detailed pathological
      characteristics of tumours for treatment planning.

PMID- 16952455
TI  - Herpes simplex virus type-1 latency inhibits dendritic growth in sympathetic
      neurons.
AB  - Herpes simplex virus type-1 (HSV-1) initially infects mucoepithelial tissues of
      the orofacial region, the eye and to a lesser extent the genitalia. Subsequently,
      the virus is retrogradely transported through the axons of the sensory and
      sympathetic neurons to their nuclei, where the virus establishes a life-long
      latent infection. During this latency period, the viral genome is
      transcriptionally silent except for a single region encoding the latency
      associated transcript (LAT). LAT has been shown to affect apoptosis, but little
      else is known regarding its effects on neurons. To understand how HSV-1 latency
      might affect dendrites in sympathetic neurons, we transfected primary cultures of
      sympathetic neurons obtained from rat embryos, with LAT expressing plasmids. LAT
      inhibited initial dendritic growth and induced dendritic retraction in
      sympathetic neurons. Latent HSV-1 infection of cultured sympathetic neurons
      inhibited dendritic growth indicating that this is likely also a consequence of
      natural infection.

PMID- 16952456
TI  - Establishing a standardized therapeutic testing protocol for spinal muscular
      atrophy.
AB  - Several mice models have been created for spinal muscular atrophy (SMA); however,
      there is still no standard preclinical testing system for the disease. We
      previously generated type III-specific SMA model mice, which might be suitable
      for use as a preclinical therapeutic testing system for SMA. To establish such a
      system and test its applicability, we first created a testing protocol and then
      applied it as a means to investigate the use of valproic acid (VPA) as a possible
      treatment for SMA. These SMA mice revealed tail/ear/foot deformity, muscle
      atrophy, poorer motor performances, smaller compound muscle action potential and
      lower spinal motoneuron density at the age of 9 to 12 months in comparison with
      age-matched wild-type littermate mice. In addition, VPA attenuates motoneuron
      death, increases spinal SMN protein level and partially normalizes motor function
      in SMA mice. These results suggest that the testing protocol developed here is
      well suited for use as a standardized preclinical therapeutic testing system for
      SMA.

PMID- 16952457
TI  - Endoscopic off-pump aortic valve replacement: does the pericardial cuff improve
      the sutureless closure of left ventricular access?
AB  - OBJECTIVE: Off-pump trans left ventricular approach provides more precise
      deployment of stented aortic valve of any size with respect to the endovascular
      replacement. One of the key steps of this procedure is the ventricle repair after
      catheter withdrawing. We designed an animal study to compare the consistency of a
      sutureless repair of the left ventricle access using nitinol occluder with and
      without pericardial cuff on the ventricular side. METHODS: Material description:
      The Amplatz-nitinol occluder consists of two square heads squeezing ventricle
      wall in between them, sealing the defect. To improve its sealing property, a
      pericardial patch was sutured to the ventricular head of the occluder. Animal
      study setup: In adult pigs, a 30F sheath was inserted into the epigastric area
      through the cardiac apex, up to the left ventricle, simulating the approach for
      off-pump aortic valve replacement. The sheath was then removed and the ventricle
      closed with standard occluder in half of the animals, and cuffed occluder in the
      other half. Animals were followed-up for 3h, collecting haemodynamics data and
      pericardial bleeding. RESULTS: Device was successfully deployed in 12 animals in
      less than 1min. In the group where the standard occluder was used, bleeding
      during the deployment was 80+/-20ml and after the deployment was 800+/-20ml over
      3h. In the group where the cuffed occluder was used, bleeding during the
      deployment was 85+/-20ml and after the deployment was 100+/-5ml over 3h. In the
      cuffed group, bleeding was significantly lower than the standard group, p-value
      being <0.001. CONCLUSIONS: The occluder is easy to use and the pericardial cuff
      dramatically increases its efficacy as demonstrated by a significant reduction of
      blood loss. The cuffed occluder opens the way for endoscopic, off-pump,
      transventricular aortic valve replacement.

PMID- 16952458
TI  - Electrospray tandem mass spectrometry analysis of S- and N-nitrosopeptides:
      facile loss of NO and radical-induced fragmentation.
AB  - The covalent addition of nitric oxide (NO) to protein thiols, a posttranslational
      modification termed S-nitrosation, is a ubiquitous event that modulates diverse
      cellular processes. The in vivo addition of NO to protein amines (N-nitrosation)
      has also been described and may similarly modify protein structure and function.
      While mass spectrometry has been employed for identification of nitrosoproteins,
      little is known about how S- and N-nitrosopeptides fragment. Such knowledge is
      important for its potential to inform on sites of protein nitrosation. Here we
      used electrospray tandem mass spectrometry to elucidate collision-induced
      dissociation (CID) features of S- and N-nitrosopeptide ions. We show that S- and
      N-nitrosopeptide ions readily lose NO, giving rise to species that contain thiyl
      and aminyl radicals, respectively. Fragmentation (MS3) of these radical peptide
      ions revealed an atypical pattern, characterized by the cleavage of select
      alphaCC and NalphaC bonds, rather than the more usual cleavage of amide bonds
      that result in b- and y-ions. These unanticipated fragmentation patterns are
      reconciled by radical-mediated abstraction of hydrogen from beta-carbon followed
      by beta-fragmentation. For thiyl radical peptides, we also observed dominant loss
      of SH and CH2SH from the Cys side-chain. Our findings provide new insights into
      the gas-phase chemistry of NO-modified peptide ions and suggest an unusual
      fragmentation pattern that may aid in future MS-based attempts to define the
      nitrosoproteome.

PMID- 16952460
TI  - Dynamic alignment of C2H4 investigated by using two linearly polarized
      femtosecond laser pulses.
AB  - We have studied multielectron ionization and Coulomb explosion of C2H4 irradiated
      by 110 fs, 800 nm laser pulses at an intensity of approximately 10(15) W/cm2.
      Strong anisotropic angular distributions were observed for the atomic ions Cn+(n
      = 1-3). Based on the results of two crossed linearly polarized laser pulses, we
      conclude that such anisotropic angular distributions result from dynamic
      alignment, in which the rising edge of the laser pulses aligns the neutral C2H4
      molecules along the laser polarization direction. The angular distribution of the
      exploding fragments, therefore, reflects the degree of the alignment of molecules
      before ionization. Using the same femtosecond laser with intensity below the
      ionization threshold, the alignment of C2H4 molecules was also observed.

PMID- 16952459
TI  - Divalent metal ion-peptide interactions probed by electron capture dissociation
      of trications.
AB  - Electron capture dissociation (ECD) of the peptide Substance P (SubP) complexed
      with divalent metals has been investigated. ECD of [SubP + H + M]3+ (M2+ = Mg2+ 
      Ba2+ and Mn2+ -Zn2+) allowed observation of a larger number of product ions than
      previous investigations of doubly charged metal-containing peptides. ECD of Mg
      Ba, Mn, Fe, and Zn-containing complexes resulted in product ions with and without
      the metal from cleavage of backbone amine bonds (c' and z* -type ions). By
      contrast, ECD of Co and Ni-containing complexes yielded major bond cleavages
      within the C-terminal methionine residue (likely to be the metal ion binding
      site). Cu-containing complexes displayed yet another behavior: amide bond
      cleavage (b and y'-type ions). We believe some results can be rationalized both
      within the hot hydrogen atom mechanism and mechanisms involving electron capture
      into excited states, such as the recently proposed amide superbase mechanism.
      However, some behavior, including formation of (cn 'M - H)+ ions for Ca-Ba, is
      best explained within the latter mechanisms with initial electron capture at the
      metal. In addition, the ECD behavior appears to correlate with the metal second
      ionization energy (IE2). Co and Ni (displaying sequestered fragmentation) have
      IE2s of 17.1 and 18.2 eV, respectively, whereas IE2s for Mg-Ba, Mn, and Fe
      (yielding random cleavage) are 10.0 to 16.2 eV. This behavior is difficult to
      explain within the hot hydrogen atom mechanism because hydrogen transfer should
      not be influenced by IE2s. However, the drastically different fragmentation
      patterns for Co, Ni, and Cu compared to the other metals can also be explained by
      their higher propensity for nitrogen (as opposed to oxygen) binding.
      Nevertheless, these results imply that directed fragmentation can be accomplished
      via careful selection of the cationizing agent.

PMID- 16952461
TI  - Application of SIMSTEX to oligomerization of insulin analogs and mutants.
AB  - The propensity of various insulins and their analogs to oligomerize was
      investigated by mass spectrometric methods including measurement of the relative
      abundances of oligomers in the gas phase and the kinetics of H/D amide exchange.
      The kinetics of deuterium uptake show a good fit when the exchanging amides are
      placed in three kinetic groups: fast, intermediate, and slow. r-Human insulin, of
      the insulins investigated, has fewer amides that exchange at intermediate rates
      and more that exchange at slow rates, in accord with its higher extent of
      association in solution. We adapted PLIMSTEX (protein ligand interactions by mass
      spectrometry, titration, and H/D exchange) to determine protein/ligand affinities
      in solution, to determine self-association equilibrium constants for proteins,
      and to apply them to various insulin analogs. We term this adaptation SIMSTEX
      (self-association interactions using mass spectrometry, self-titration and H/D
      exchange); it gives affinity constants that compare well with the literature
      results. The results from SIMSTEX show that some mutants (e.g., GlnB13) have an
      increased tendency to self-associate, possibly slowing down their action in vivo.
      Other mutants (e.g., lispro and AspB9) have lower propensities for self
      association, thus providing potentially faster-acting analogs for use in
      controlling diabetes.

PMID- 16952462
TI  - Generation and detection of multiply-charged peptides and proteins by matrix
      assisted laser desorption electrospray ionization (MALDESI) Fourier transform ion
      cyclotron resonance mass spectrometry.
AB  - We report the coupling of a hybrid ionization source, matrix-assisted laser
      desorption electrospray ionization (MALDESI), to a Fourier transform-ion
      cyclotron resonance mass spectrometer (FT-ICR MS). The details of the source
      design and initial data are presented. Analysis of peptides and proteins ranging
      from 1 to 8.6 kDa resulted in high resolving power single-acquisition FT-ICR mass
      spectra with average charge-states highly correlated to those obtained by
      nanoESI, thus, providing strong evidence that the ESI process dictates the
      observed charge-state distribution. Importantly, unlike the recently introduced
      electrospray assisted laser desorption ionization (ELDI) source reported by Shiea
      and coworkers [1, 2], the data we have obtained to date rely on the use of an
      organic acid matrix. The results presented herein provide insight into the
      charging mechanism of this emerging ionization approach, while also expanding the
      utility of FT-ICR MS for top-down protein and complex mixture analysis.

PMID- 16952463
TI  - The carboxypeptidase-like substrate-binding site in Nna1 is essential for the
      rescue of the Purkinje cell degeneration (pcd) phenotype.
AB  - The Purkinje cell degeneration (pcd) phenotype is characterized by adult onset
      neurodegeneration resulting from mutations in Nna1, a gene encoding an
      intracellular protein with a putative metallocarboxypeptidase domain. As Nna1 is
      also induced in axotomized motor neurons, the elucidation of its function can
      shed light on previously unsuspected mechanisms common to degenerative and
      regenerative responses. Structural modeling revealed that Nna1 and three related
      gene products constitute a new subfamily of metallocarboxypeptidases with a
      distinctive substrate-binding site. To test whether the metallocarboxypeptidase
      domain is functionally essential, transgenic mice were generated that expressed
      Nna1 or a substrate-binding site mutant of Nna1 selectively in Purkinje cells
      using the L7/pcp2 promoter. When bred onto a homozygous pcd(3J) background, wild
      type but not mutant Nna1 rescued ataxic behavior and Purkinje cell loss.
      Therefore, loss of Nna1 in Purkinje cells leads directly to their degeneration
      and Nna1's carboxypeptidase domain is essential for survival of these neurons.

PMID- 16952464
TI  - Dendrite-selective redistribution of the chemokine receptor CXCR4 following
      agonist stimulation.
AB  - The chemokine SDF-1 is a secreted protein that plays a critical role in several
      aspects of neuron development through interaction with its unique receptor CXCR4.
      A key mechanism that controls neuron responsiveness to extracellular signals
      during neuronal growth is receptor endocytosis. Since we previously reported that
      SDF-1 regulates axon development without affecting the other neurites, we asked
      whether this could correlate with a compartment-selective trafficking of CXCR4.
      We thus studied CXCR4 behavior upon SDF-1 exposure in rat hippocampus slices and
      in transfected neuron cultures. A massive agonist-induced redistribution of CXCR4
      in endosomes was observed in dendrites whereas no modification was evidenced in
      axons. Our data suggest that CXCR4 trafficking may play a role in mediating
      selective effects of SDF-1 on distinct neuronal membrane subdomains.

PMID- 16952465
TI  - Pre- and postsynaptic actions of L1-CAM in nicotinic pathways.
AB  - Cell adhesion molecules (CAMs) have long been known to guide axon outgrowth and
      pathfinding. More recent evidence indicates they contribute to synapse formation
      as well. The L1 family of IgCAMs has been implicated in long-term potentiation,
      learning, and some features of synaptic structure. We show here that L1 is
      localized in nicotinic pathways at both pre- and postsynaptic sites. In the chick
      ciliary ganglion, postsynaptic L1 is associated with nicotinic receptors and
      potentiates their downstream signaling. Postsynaptic L1 is also important for
      aligning presynaptic structures over the postsynaptic cell. Dominant negative
      experiments suggest this latter effect depends on homophilic interactions with
      presynaptic L1. At the neuromuscular junction L1 is also found presynaptically
      where dominant negative experiments again indicate a role in aligning presynaptic
      structures over postsynaptic receptors, both in culture and in vivo. These
      findings identify new roles for L1 at nicotinic synapses and underscore the
      multipotency of L1-CAMs.

PMID- 16952466
TI  - Detecting fearful and neutral faces: BOLD latency differences in amygdala
      hippocampal junction.
AB  - Evolutionary survival and procreation are augmented if an individual organism
      quickly detects environmental threats and rapidly initiates defensive behavioral
      reactions. Thus, facial emotions signaling a potential threat, e.g., fear or
      anger, should be perceived rapidly and automatically, possibly through a
      subcortical processing route which includes the amygdala. Using event-related
      functional magnetic resonance imaging (fMRI), we investigated the time course of
      the response in the amygdala to neutral and fearful faces, which appear from
      dynamically decreasing random visual noise. We aimed to detect differences of the
      amygdala response between fearful and neutral faces by estimating the latency of
      the blood oxygenation level-dependent (BOLD) response. We found that bilateral
      amygdala-hippocampal junction activation occurred earlier for fearful than for
      neutral faces. Our findings support the theory of a dual route architecture in
      which the subcortical thalamic-hippocampal-amygdala route serves fast
      preconscious threat perception.

PMID- 16952467
TI  - Cluster-based analysis of FMRI data.
AB  - We propose a method for the statistical analysis of fMRI data that tests cluster
      units rather than voxel units for activation. The advantages of this analysis
      over previous ones are both conceptual and statistical. Recognizing that the
      fundamental units of interest are the spatially contiguous clusters of voxels
      that are activated together, we set out to approximate these cluster units from
      the data by a clustering algorithm especially tailored for fMRI data. Testing the
      cluster units has a two-fold statistical advantage over testing each voxel
      separately: the signal to noise ratio within the unit tested is higher, and the
      number of hypotheses tests compared is smaller. We suggest controlling FDR on
      clusters, i.e., the proportion of clusters rejected erroneously out of all
      clusters rejected and explain the meaning of controlling this error rate. We
      introduce the powerful adaptive procedure to control the FDR on clusters. We
      apply our cluster-based analysis (CBA) to both an event-related and a block
      design fMRI vision experiment and demonstrate its increased power over voxel-by
      voxel analysis in these examples as well as in simulations.

PMID- 16952468
TI  - Reducing interscanner variability of activation in a multicenter fMRI study:
      controlling for signal-to-fluctuation-noise-ratio (SFNR) differences.
AB  - Variation in scanner performance will lead to variation in activation patterns in
      multicenter fMRI studies. The purpose of this investigation was to evaluate the
      effect of statistically covarying for scanner differences in signal-to
      fluctuation-noise-ratio (SFNR) on reducing scanner differences in activation
      effect size as part of a multicenter fMRI project (FIRST BIRN). For SFNR,
      "signal" is typically the mean intensity over time and "fluctuation noise" is the
      temporal standard deviation. Five subjects were sent to 9 centers (10 scanners)
      and scanned on two consecutive days using a sensorimotor fMRI protocol. High
      field (4 T and 3 T) and low-field (1.5 T) scanners from three vendors (GE,
      Siemens and Picker) were included. The effect size for the detection of neural
      activation during a sensorimotor task was evaluated as the percent of temporal
      variance accounted for by our model (percent of variance accounted for, or PVAF).
      Marked scanner effects were noted for both PVAF as well as SFNR. After covariate
      adjustment with one of several measures of SFNR, there were dramatic reductions
      in scanner-to-scanner variations in activation effect size. Variance components
      analyses revealed 75%-81% reductions in variance due to scanner with this method.
      Thus, controlling for scanner variation in SFNR may be an effective method to
      homogenize activation effect sizes in multicenter studies.

PMID- 16952469
TI  - Source imaging of the cortical 10 Hz oscillations during cooling and warming in
      humans.
AB  - Primary cold and warm afferent fibers show a robust overshoot in their firing
      during periods of temperature change, which subsides during tonic thermal
      stimulation. Our objective was to analyze cortical activation, on a scale of
      hundreds of milliseconds, occurring during the process of dynamic cooling and
      warming, based on an evaluation of the amplitude changes seen in 10 Hz
      electroencephalographic oscillations. Eleven right-handed subjects were exposed
      to innocuous cold ramp stimuli (from 32 degrees C to 22 degrees C, 10 degrees
      C/s) and warm ramp stimuli (32 degrees C to 42 degrees C, 10 degrees C/s) on the
      thenar region of their right palm, using a contact thermode. EEG was recorded
      from 111 scalp sites, and the 10 Hz current source densities were modeled using
      low-resolution electromagnetic tomography. During cooling, the earliest amplitude
      decreases of 10 Hz oscillations were seen in the contralateral posterior insula
      and secondary somatosensory cortex (SII), and the premotor cortex (PMC). During
      warming, the earliest events were only observed in the PMC and occurred
      approximately 0.7 s later than during cooling. Linear regression analysis between
      10 Hz current source densities and temperature variations revealed cooling
      sensitive activation in the bilateral posterior insula, PMC and the anterior
      cingulate cortex. During warming, the amplitude of 10 Hz oscillations in the PMC
      and posterior insula correlated with stimulus temperature. Dynamic thermal
      stimulation activates, in addition to the posterior insula and parietal
      operculum, the lateral PMC. The activation of the anterior cingulate cortex
      during cooling may aid in the anticipation of the cold temperature end-point and
      provide continuous evaluation of the thermal stimulus.

PMID- 16952470
TI  - Identification of novel candidate genes for globin regulation in erythroid cells
      containing large deletions of the human beta-globin gene cluster.
AB  - The genetic mechanisms underlying the continued expression of the gamma-globin
      genes during the adult stage in deletional hereditary persistence of fetal
      hemoglobin (HPFH) and deltabeta-thalassemias are not completely understood.
      Herein, we investigated the possible involvement of transcription factors, using
      the suppression subtractive hybridization (SSH) method as an initial screen to
      identify differentially expressed transcripts in reticulocytes from a normal and
      a HPFH-2 subject. Some of the detectable transcripts may participate in globin
      gene regulation. Quantitative real-time PCR (qRT-PCR) experiments confirmed the
      downregulation of ZHX2, a transcriptional repressor, in two HPFH-2 subjects and
      in a carrier of the Sicilian deltabeta-thalassemia trait. The chromatin
      remodeling factors ARID1B and TSPYL1 had a very similar pattern of expression
      with an incremental increase in HPFH and decreased expression in deltabeta
      thalassemia. These differences suggest a mechanism to explain the heterocellular
      and pancellular distribution of fetal hemoglobin in deltabeta-thalassemia and
      deletional HPFH, respectively. Interestingly, alpha-globin mRNA levels were
      decreased, similar to beta-globin in all reticulocyte samples analyzed.

PMID- 16952471
TI  - Bilateral basal ganglia involvement in a patient with Griscelli syndrome.
AB  - We report a 6-year-old Iranian boy with silvery-gray hair, eyelashes and the
      eyebrows who was admitted because of seizures and subsequent stupor. He had
      previous history of acute hemiparesis at 1 year of age and hepatitis-like
      syndrome 3 months ago. Microscopic examination of the patient's hair shaft
      revealed different sized clumps of melanin seen in the center of the shafts. Bone
      marrow aspiration revealed erythroid hyperplasia and erythrophagocytic cells.
      Bilateral frontal cortical and subcortical high signal lesions, dirty white
      matter, high signal areas in the upper pons and in both caudates and lentiform
      nuclei in T2 WI were the brain MRI findings of the patient. He died in the
      accelerated phase of Griscelli Syndrome (GS) type 2. To our knowledge we report
      the first case of GS from Iran.

PMID- 16952472
TI  - Acute fright induces onset of symptoms in vanishing white matter disease-case
      report.
AB  - Vanishing white matter disease is a newly recognised leukoencephalopathy of
      identified genetic background, characterised by cystic degeneration and
      progressive vanishing of white matter. The characteristic clinical symptoms are
      spasticity and ataxia with relatively preserved cognitive functions. A
      characteristic feature of the disease is the occurrence of the symptoms after a
      physical stress situation such as mild head trauma or febrile infection. We would
      like to present a case of a 6-year-old girl whose first symptoms of the disease
      occurred after being frightened by a horse.

PMID- 16952473
TI  - +H-proton-magnetic resonance spectroscopic findings in a patient with acute
      hemicerebellitis presenting without localized signs: a case report.
AB  - Acute cerebellitis (AC) is an inflammatory process involving the cerebellum.
      Usually, this pathology is bilateral; it is unusual to have a unilateral
      cerebellitis. Only seven cases of hemicerebellitis have been reported in the
      literature. Here, we review the literature and report the magnetic resonance
      imaging (MRI) and proton-magnetic resonance spectroscopic (+H-MRS) findings of a
      case of acute hemicerebellitis in a 15-year-old girl presenting with 15 days'
      history of headache.

PMID- 16952475
TI  - [Functional MRI in brain tumours].
AB  - Functional MRI is a technique of imaging which is developing fast as it allows
      non-aggressive evaluation of brain functions. Diffusion, perfusion and activation
      are each used to study brain responsiveness to a given task. As a pretherapeutic
      routine investigation, in brain tumours, it can be helpful as an additional tool
      to morphological MRI in evaluating the prognosis of patients.

PMID- 16952474
TI  - [Prognostic factors and management of rare cancers].
AB  - The management of rare cancers is controversial. The role of adjuvant therapies,
      such as chemotherapy and radiation therapy remains unclear. The limited number of
      patients included in the studies cannot generally allow any consistent
      statistical analysis to determine either prognostic factors or the impact of
      surgery and adjuvant therapies on local control and long-term survival. The Rare
      Cancer Network is a multi-institutional cooperative group created in 1993 to
      initiate large retrospective studies on rare cancers with the aim of improving
      our knowledge in terms of management, outcome, and prognostic factors of such
      tumors. The network gathers more than 70 institutions from 21 countries. So far,
      32 projects have been carried out. In this report we will discuss the most
      significant data provided by our group in several investigated diseases.

PMID- 16952477
TI  - Spinal metastasis from a primary parotid carcinoma: a case report.

PMID- 16952476
TI  - High resolution radiographic and fine immunologic definition of TB disease
      progression in the rhesus macaque.
AB  - Mycobacterium tuberculosis infection in non-human primates parallels human
      tuberculosis, and provides a valuable vaccine evaluation model. However, this
      model is limited by the availability of real-time, non-invasive information
      regarding disease progression. Consequently, we have combined computed tomography
      scanning with enumeration of antigen-specific T cell responses. Four rhesus
      monkeys were infected with M. tuberculosis strain H37Rv (1000 cfu) in the right
      lower lobe via a bronchoscope. All uniformly developed progressive tuberculosis,
      and required euthanasia at 12 weeks. Computed tomography scanning provided
      detailed real-time imaging of disease progression. At necropsy, computed
      tomography and pathohistologic findings were tightly correlated, and
      characteristic of human disease. Immunologic monitoring demonstrated progressive
      evolution of high frequency M. tuberculosis-specific CD4(+) and CD8(+) T cell
      responses. Peripheral blood effector cell frequencies were similar to those
      observed in tissues. In summary, computed tomography scanning in conjunction with
      immunologic monitoring provides a non-invasive, accurate, and rapid assessment of
      tuberculosis in the non-human primate.

PMID- 16952478
TI  - Kinematic response characteristics of the CAREN moving platform system for use in
      posture and balance research.
AB  - The CAREN system is a new and unique device for use in postural and balance
      research in clinical settings due to its ability to independently perturb the
      support surface in each of six degrees of freedom. Users of this system need
      knowledge of its technical performance which is not available. The aim of this
      study was to determine the technical performance of the CAREN system by defining
      its kinematic response characteristics to two commonly used input functions (sine
      and ramp) for each of its six translational and rotational axes. The
      translational and rotational displacement, velocity and acceleration limits of
      the CAREN system suggest that it is a mid-range system with regard to single
      degree of freedom moving platform devices reported in the literature. The maximum
      average displacement cross-talk was 1.5% of the viable working range in any
      specified direction. The maximum average velocity cross-talk was 3.3% of its
      maximum velocity in any specified direction. The CAREN system was able to respond
      to ramp input functions within its displacement and velocity limits although, for
      short duration ramps, there was evidence that target velocity was not reached. It
      is concluded that the CAREN system is an appropriate device for postural and
      balance research with some unique features. This specification of its technical
      performance should help researchers to identify the tasks for which it is most
      suitable.

PMID- 16952479
TI  - Moyamoya disease presenting with paroxysmal exercise-induced dyskinesia.
AB  - We report a patient with moyamoya disease presenting with paroxysmal exercise
      induced dyskinesia (PED). A 31-year-old lathe man developed recurrent attacks of
      paroxysmal hemichorea. The attacks always affected his left limbs and occurred
      either after several hours of working or while playing football. The duration of
      attacks ranged from 30 min to 4h. Attacks were not provoked by sudden movements,
      consumption of coffee or alcohol, hyperventilation, emotional stress, exposure to
      cold or passive movement. An MRI of the brain showed no parenchymal lesions.
      However, (99m)Tc-ethylcysteine dimer SPECT study showed hypoperfusion in the
      right striatum. Digital subtraction angiography showed stenosis of the right
      internal carotid and middle cerebral artery with prominent basal collaterals,
      which was compatible with moyamoya disease. Imaging studies of the cerebral
      arteries should be done in patients with clinical features of PED in order to
      detect possible cases of moyamoya disease.

PMID- 16952480
TI  - Oxidative stress and DNA damage induced by a drinking-water chlorination
      disinfection byproduct 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX)
      in mice.
AB  - 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a water chlorine
      disinfection byproduct, can induce DNA damage (e.g., modification of nucleotides
      and DNA strand breaks) and subsequent DNA repair in vitro. However, the
      underlying mechanism(s) how DNA damage is induced by MX is unknown. We
      hypothesized that MX may cause oxidative stress that leads to DNA damage in vivo.
      In the present study, we exposed groups of mice to MX at concentrations of 0
      (solvent control), 11 (low), 33 (medium) and 99 (high) mg/kg b.w. by single
      intraperitoneal injection. After treating the mice for 3h, we detected cellular
      levels of malondialdehyde (MDA) and glutathione (GSH) to assess oxidative stress
      in the target cells. In addition, we also evaluated DNA damage using single cell
      gel electrophoresis (SCGE or Comet assay). We found that the levels of DNA damage
      in all cell types were correlated positively with levels of MDA but negatively
      with levels of GSH (P<0.05 for all). Also, there were negative correlations
      between levels of MDA and GSH (r=-0.995 for liver cells, -0.916 for kidney cells,
      -0.975 for intestine cells, respectively; P<0.05 for all but kidney cells). Our
      findings suggest that MX may induce DNA damage by the mechanism of causing
      cellular oxidative stress as measured by increased MDA and decreased GSH, at
      least in mice.

PMID- 16952481
TI  - Activation of human inflammatory cells by secreted phospholipases A2.
AB  - Secreted phospholipases A(2) (sPLA(2)s) are enzymes detected in serum and
      biological fluids of patients with various inflammatory, autoimmune and allergic
      disorders. Different isoforms of sPLA(2)s are expressed and released by human
      inflammatory cells, such as neutrophils, eosinophils, T cells, monocytes,
      macrophages and mast cells. sPLA(2)s generate arachidonic acid and
      lysophospholipids thus contributing to the production of bioactive lipid
      mediators in inflammatory cells. However, sPLA(2)s also activate human
      inflammatory cells by mechanisms unrelated to their enzymatic activity. Several
      human and non-human sPLA(2)s induce degranulation of mast cells, neutrophils and
      eosinophils and activate exocytosis in macrophages. In addition some, but not
      all, sPLA(2) isoforms promote cytokine and chemokine production from macrophages,
      neutrophils, eosinophils, monocytes and endothelial cells. These effects are
      primarily mediated by binding of sPLA(2)s to specific membrane targets (heparan
      sulfate proteoglycans, M-type, N-type or mannose receptors) expressed on effector
      cells. Thus, sPLA(2)s may play an important role in the initiation and
      amplification of inflammatory reactions by at least two mechanisms: production of
      lipid mediators and direct activation of inflammatory cells. Selective inhibitors
      of sPLA(2)-enzymatic activity and specific antagonists of sPLA(2) receptors are
      current being tested for pharmacological treatment of inflammatory and autoimmune
      diseases.

PMID- 16952482
TI  - Genetic Diversity of Microbial Eukaryotes in Anoxic Sediment of the Saline
      Meromictic Lake Namako-ike (Japan): On the Detection of Anaerobic or Anoxic
      tolerant Lineages of Eukaryotes.
AB  - Available sequence data on eukaryotic small-subunit ribosomal DNA (SSU rDNA)
      directly retrieved from various environments have increased recently, and the
      diversity of microbial eukaryotes (protists) has been shown to be much greater
      than previously expected. However, the molecular information accumulated to date
      does still not thoroughly reveal ecological distribution patterns of microbial
      eukaryotes. In the ongoing challenge to detect anaerobic or anoxic-tolerant
      lineages of eukaryotes, we directly extracted DNA from the anoxic sediment of a
      saline meromictic lake, constructed genetic libraries of PCR-amplified SSU rDNA,
      and performed phylogenetic analyses with the cloned SSU rDNA sequences. Although
      a few sequences could not be confidently assigned to any major eukaryotic groups
      in the analyses and are debatable regarding their taxonomic positions, most
      sequences obtained have affiliations with known major lineages of eukaryotes
      (Cercozoa, Alveolata, Stramenopiles, and Opisthokonta). Among these sequences,
      some branched with lineages predominantly composed of uncultured environmental
      clones retrieved from other anoxic environments, while others were closely
      related to those of eukaryotic parasites (e.g. Phytomyxea of Cercozoa, Gregarinea
      of Alveolata, and Ichthyosporea of Opisthokonta).

PMID- 16952483
TI  - A systematic review of guidelines for the prevention of heat illness in community
      based sports participants and officials.
AB  - This paper presents the findings of a systematic review of guidelines on
      preventing heat illness in sports participants and officials. University library
      databases and Internet sources were searched for guidelines pertaining to
      community-based sports, and occupational health and safety, using a comprehensive
      list of search terms. Guidelines were included if they met the criteria of
      English language, full text and fully referenced, and dealt specifically with, or
      could be extrapolated to, prevention of heat illness in sports participants and
      officials. Guideline inclusion was evaluated by two independent reviewers, who
      also independently assessed guideline quality using the AGREE instrument. Common
      guideline themes were identified by synthesis and recommendations for each theme
      were extracted. A synthesis of recommendations for common themes was then
      undertaken. Thirteen eligible guidelines were included. Thirty-two guidelines
      were excluded, as they did not provide sufficient information on construction or
      references. The methodological quality of the included guidelines was variable.
      The evidence-base of the guidelines varied, reflecting primary and secondary
      research. While five common heat-illness prevention themes were identified (fluid
      intake, heat limits, clothing, acclimatisation, precautionary interventions),
      variable recommendations were made pertaining to these themes. This potentially
      reflected the variable underpinning evidence of the guidelines. This review
      highlighted the need for better quality guideline construction related to
      defensible and transparent evidence sources regarding sports participation in hot
      weather. The synthesised recommendations cautiously provide a framework of
      current best evidence upon which sporting organisations internationally can base
      strategies for safe participation in the heat.

PMID- 16952484
TI  - TNFalpha genotype influences development of IgA-ASCA antibodies in Crohn's
      disease patients with CARD15 wild type.
AB  - A typical feature of Crohn's disease (CD) patients is the development of
      antibodies against self- (PAB) or exogenous (ASCA) antigens, a process in which
      mucosal cytokine expression pattern might be involved. On the other hand,
      mutations in CARD15, a genetic risk factor for CD, alter cytokine production in
      response to bacterial infection. In the present study, we evaluated the role of
      functionally relevant IL-10 and TNFalpha gene polymorphisms in the synthesis of
      these antibodies and their relationship with CARD15 mutations. In CARD15 wild
      type patients, high TNFalpha producer genotypes protect against IgA-ASCA
      development, whereas an inverse association was observed in autoantibody
      synthesis (PAB). These associations were not observed in patients with CARD15
      mutations, probably due to the lack of TNFalpha release as a consequence of the
      failure of CARD15 protein to recognize the peptidoglycan. Thus, we proposed a
      CARD15-TNFalpha circuit that might play a role in mucosal immune surveillance.

PMID- 16952485
TI  - Characterization of DitA3, the [Fe3S4] ferredoxin of an aromatic ring
      hydroxylating dioxygenase from a diterpenoid-degrading microorganism.
AB  - DitA3, a small soluble ferredoxin, is a component of a ring-hydroxylating
      dioxygenase involved in the microbial degradation of the diterpenoid,
      dehydroabietic acid. The anaerobic purification of a heterologously expressed his
      tagged DitA3 yielded 20 mg of apparently homogeneous recombinant protein,
      rcDitA3, per liter of cell culture. Each mole of purified rcDitA3 contained 2.9
      equivalents of iron and 4.2 equivalents of sulfur, indicating the presence of a
      single [Fe(3)S(4)] cluster. This conclusion was corroborated by UV-Visible
      absorption (epsilon(412)=13.4 mM(-1) cm(-1)) and EPR (g(x,y)=2.00 and g(z)=2.02)
      spectroscopies. The reduction potential of rcDitA3, determined using a highly
      oriented parallel graphite (HOPG) electrode, was -177.0+/-0.5 mV vs. the standard
      hydrogen electrode (SHE) (20 mM MOPS, 80 mM KCl, pH 7.0, 22 degrees C). This
      potential is similar to those of small, soluble Rieske-type ferredoxin components
      of aromatic-ring dihydroxylating dioxygenases. In contrast to these Rieske-type
      ferredoxins, DitA3 appears to exist as a dimer in solution. The dimeric
      ferredoxin may be more stable or may increase the catalytic efficiency of the
      dioxygenase by delivering the two reducing equivalents required for turnover of
      the oxygenase.

PMID- 16952486
TI  - Protein sulfation analysis--A primer.
AB  - The aim of this review is to present an overview of protein sulfation in the
      context of 'modificomics', i.e. post-translational modification-specific proteome
      research. In addition to a short introduction to the biology of protein sulfation
      (part 1), we will provide detailed discussion regarding (i) methods and tools for
      prediction of protein tyrosine sulfation sites (part 2), (ii) biochemical
      techniques used for protein sulfation analysis (part 3.1), and (iii) mass
      spectrometric strategies and methods applied to protein sulfation analysis (part
      3.2). We will highlight strengths and limitations of different strategies and
      approaches (including references), providing a primer for newcomers to protein
      sulfation analysis.

PMID- 16952487
TI  - Use of microdosing to predict pharmacokinetics at the therapeutic dose:
      experience with 5 drugs.
AB  - OBJECTIVES: A volunteer trial was performed to compare the pharmacokinetics of 5
      drugs--warfarin, ZK253 (Schering), diazepam, midazolam, and erythromycin--when
      administered at a microdose or pharmacologic dose. Each compound was chosen to
      represent a situation in which prediction of pharmacokinetics from either animal
      or in vitro studies (or both) was or is likely to be problematic. METHODS: In a
      crossover design volunteers received (1) 1 of the 5 compounds as a microdose
      labeled with radioactive carbon (carbon 14) (100 microg), (2) the corresponding
      (14)C-labeled therapeutic dose on a separate occasion, and (3) simultaneous
      administration of an intravenous (14)C-labeled microdose and an oral therapeutic
      dose for ZK253, midazolam, and erythromycin. Analysis of (14)C-labeled drugs in
      plasma was done by use of HPLC followed by accelerator mass spectrometry. Liquid
      chromatography-tandem mass spectrometry was used to measure plasma concentrations
      of ZK253, midazolam, and erythromycin at therapeutic concentrations, whereas HPLC
      accelerator mass spectrometry was used to measure warfarin and diazepam
      concentrations. RESULTS: Good concordance between microdose and therapeutic dose
      pharmacokinetics was observed for diazepam (half-life [t((1/2))] of 45.1 hours,
      clearance [CL] of 1.38 L/h, and volume of distribution [V] of 90.1 L for 100
      microg and t((1/2)) of 35.7 hours, CL of 1.3 L/h, and V of 123 L for 10 mg),
      midazolam (t((1/2)) of 4.87 hours, CL of 21.2 L/h, V of 145 L, and oral
      bioavailability [F] of 0.23 for 100 microg and t((1/2)) of 3.31 hours, CL of 20.4
      L/h, V of 75 L, and F of 0.22 for 7.5 mg), and development compound ZK253 (F =
      <1% for both 100 microg and 50 mg). For warfarin, clearance was reasonably well
      predicted (0.17 L/h for 100 microg and 0.26 L/h for 5 mg), but the discrepancy
      observed in distribution (67 L for 100 microg and 17.9 L for 5 mg) was probably a
      result of high-affinity, low-capacity tissue binding. The oral microdose of
      erythromycin failed to provide detectable plasma levels as a result of possible
      acid lability in the stomach. Absolute bioavailability for the 3 compounds
      examined yielded excellent concordance with data from the literature or data
      generated in house. CONCLUSION: Overall, when used appropriately, microdosing
      offers the potential to aid in early drug candidate selection.

PMID- 16952488
TI  - A positron emission tomography microdosing study with a potential antiamyloid
      drug in healthy volunteers and patients with Alzheimer's disease.
AB  - This work describes a microdosing study with an investigational, carbon 11
      labeled antiamyloid drug, 1,1'-methylene-di-(2-naphthol) (ST1859), and positron
      emission tomography (PET) in healthy volunteers (n = 3) and patients with
      Alzheimer's disease (n = 6). The study aimed to assess the distribution and local
      tissue pharmacokinetics of the study drug in its target organ, the human brain.
      Before PET studies were performed in humans, the toxicologic characteristics of
      ST1859 were investigated by an extended single-dose toxicity study according to
      guidelines of the Food and Drug Administration and European Medicines Agency,
      which are relevant for clinical trials with a single microdose. After intravenous
      bolus injection of 341 +/- 21 MBq [(11)C]ST1859 (containing <11.4 nmol of
      unlabeled ST1859), peripheral metabolism was rapid, with less than 20% of total
      plasma radioactivity being in the form of unchanged parent drug at 10 minutes
      after administration. In both the control and patient groups, uptake of
      radioactivity into the brain was relatively fast (time to reach maximum
      concentration, 9-17 minutes) and pronounced (maximum concentration [standardized
      uptake value], 1.3-2.2). In both healthy volunteers and patients, there was a
      rather uniform distribution of radioactivity in the brain, including both amyloid
      beta-rich and -poor regions, with slow washout of radioactivity (half-life, 82
      185 minutes). In conclusion, these data provide important information on the
      blood-brain barrier penetration and metabolism of an investigational antiamyloid
      drug and suggest that the PET microdosing approach is a useful method to describe
      the target-organ pharmacokinetics of radiolabeled drugs in humans.

PMID- 16952489
TI  - The erythromycin breath test reflects P-glycoprotein function independently of
      cytochrome P450 3A activity.
AB  - BACKGROUND: The erythromycin breath test (ERBT) has been widely used as a
      phenotypic measure of cytochrome P450 (CYP) 3A activity in individuals, as well
      as its modulation by inhibitors or inducers. However, it is not entirely clear
      what this measure actually reflects because, in addition to CYP3A, animal studies
      suggest that P-glycoprotein is also involved in erythromycin's hepatic
      disposition. Thus studies were undertaken to determine the effect of tariquidar,
      a potent P-glycoprotein inhibitor that does not affect CYP3A activity, on the
      ERBT and on the CYP3A-mediated metabolism of midazolam, a non-P-glycoprotein
      substrate. METHODS: A randomized, double-blind, 2-way crossover trial was
      performed in 8 healthy subjects involving the intravenous administration of
      either placebo or tariquidar (150 mg over a period of 30 minutes) on 2 study days
      2 weeks apart. On both days, a 1-hour ERBT was performed, followed by
      determination of midazolam's systemic clearance after a 1-mg intravenous dose.
      RESULTS: Tariquidar increased the ERBT 1-hour value in all subjects (median, 2.1%
      [interquartile range (IQR), 1.9% to 3.3%] versus 5.4% [IQR, 3.7% to 7.8%] for
      placebo and tariquidar, respectively; P = .012), representing a median 2.3-fold
      (IQR, 1.9- to 3.0-fold) increase. By contrast, midazolam's systemic clearance
      after tariquidar was unchanged (median change, -4.6% [IQR, -10.2% to 10.7%]; P =
      .78). CONCLUSIONS: Hepatic P-glycoprotein is an important determinant of the ERBT
      and a potentially confounding factor in interpreting the meaning of the trait
      measure. In addition, the results demonstrate the dynamic interplay between
      hepatic drug metabolism and transport of dual CYP3A/P-glycoprotein substrates.

PMID- 16952490
TI  - Liver disease selectively modulates cytochrome P450--mediated metabolism.
AB  - BACKGROUND: The liver plays a significant role in drug metabolism; thus it would
      be expected that liver disease may have a detrimental effect on the activity of
      cytochrome P450 (CYP) enzymes. The extent to which the presence and severity of
      liver disease affect the activity of different individual drug-metabolizing
      enzymes is still not well characterized. The purpose of this study was to assess
      the effect of liver disease on multiple CYP enzymes by use of a validated
      cocktail approach. METHODS: The participants in this investigation were 20
      patients with different etiologies and severity of liver disease and 20 age-, sex
      , and weight-matched healthy volunteers. Liver disease severity was categorized
      by use of the Child-Pugh score. All participants received a cocktail of 4 oral
      drugs simultaneously, caffeine, mephenytoin, debrisoquin (INN, debrisoquine), and
      chlorzoxazone, as in vivo probes of the drug-metabolizing enzymes CYP1A2,
      CYP2C19, CYP2D6, and CYP2E1, respectively. The primary end points were
      measurements of specific CYP metabolism indexes for each enzyme. RESULTS:
      Mephenytoin metabolism was significantly decreased in both patients with mild
      liver disease (Child-Pugh score of 5/6) (-63% [95% confidence interval (CI), -86%
      to -40%]; P = .0003) and patients with moderate to severe liver disease (Child
      Pugh score >6) (-80% [95% CI, -95% to -64%]; P = .0003). In comparison with
      control subjects, the caffeine metabolic ratio was 69% lower (95% CI, -85% to 
      54%; median, 0.14 versus 0.62; P = .0003), the debrisoquin recovery ratio was 71%
      lower (95% CI, -96% to -47%; median, 0.10 versus 0.65; P = .012), and the
      chlorzoxazone metabolic ratio was 60% lower (95% CI, -91% to -29%; median, 0.21
      versus 0.83; P = .0111) in patients with moderate to severe liver disease. All 4
      drugs showed significant negative relationships with the Child-Pugh score.
      CONCLUSIONS: CYP enzyme activity is differentially affected by the presence of
      liver disease. We propose that the data can be explained by the "sequential
      progressive model of hepatic dysfunction," whereby liver disease severity has a
      differential effect on the metabolic activity of specific CYP enzymes.

PMID- 16952491
TI  - Pharmacodynamics and pharmacokinetics of the urotensin II receptor antagonist
      palosuran in macroalbuminuric, diabetic patients.
AB  - OBJECTIVE: In patients with renal disease increased urotensin II plasma levels
      have been observed. We have investigated whether palosuran, a potent, selective,
      and competitive antagonist of the urotensin II receptor, has effects in patients
      who are prone to the development of renal disease. METHODS: Macroalbuminuric,
      diabetic patients, categorized by renal function, were treated with oral doses of
      125 mg palosuran twice daily for 13.5 days in addition to treatment with either
      an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker.
      The 24-hour urinary albumin excretion rate was determined twice at baseline and
      after 13.5 days of treatment. Plasma concentrations of palosuran were determined
      for 12 hours after the first and last drug intake. Renal hemodynamics was
      measured before and after 12.5 days of treatment. Tolerability and safety
      parameters were monitored. RESULTS: An overall clinically significant reduction
      of 24.3% (geometric mean) (95% confidence interval, 4.1 to 45.0) in the 24-hour
      urinary albumin excretion rate was observed (P = .014). No effect was observed on
      renal hemodynamic parameters. Palosuran was rapidly absorbed with maximum plasma
      concentrations at 1 hour after drug administration. The accumulation factor was
      1.7 (geometric mean) (95% confidence interval, 1.3 to 2.1). Palosuran was well
      tolerated. CONCLUSIONS: The good tolerability profile and the decrease in the 24
      hour urinary albumin excretion rate may benefit diabetic patients with renal
      failure with regard to their disease progression. Larger placebo-controlled
      trials in this patient population are needed to investigate whether urotensin II
      receptor antagonists, given as monotherapy or combination therapy, may improve
      the current treatment of diabetic nephropathy.

PMID- 16952492
TI  - Validation of incorporating flurbiprofen into the Pittsburgh cocktail.
AB  - BACKGROUND: We have previously shown that flurbiprofen metabolism to 4'
      hydroxyflurbiprofen provides an in vivo measure of cytochrome P450 (CYP) 2C9
      activity. This study evaluated the possibility of incorporating flurbiprofen into
      the current 5-drug Pittsburgh cocktail. METHODS: In a randomized, 3-way, Latin
      square, crossover-design study, 24 healthy subjects (mean age [+/-SD], 47.8 +/-
      15.1 years) received flurbiprofen (50 mg) and the Pittsburgh 5-drug cocktail (100
      mg caffeine, 100 mg mephenytoin, 10 mg debrisoquin [INN, debrisoquine], 250 mg
      chlorzoxazone, and 100 mg dapsone) separately and in combination on 3 occasions
      over a period of 5 weeks. Urine was collected from 0 to 8 hours, and plasma was
      obtained at 4 and 8 hours after drug administration. Parent drug and metabolite
      concentrations were measured to determine phenotypic indices for each of the
      metabolizing enzymes. RESULTS: The geometric mean ratio and 90% confidence
      interval of the phenotypic indices were included within the 80% to 125%
      bioequivalence range for each of the probe drugs. There were no statistically
      significant differences between the phenotypic indices determined after
      administration of the 5-drug and 6-drug cocktails. However, there was a small but
      statistically significant increase (7.5%, P = .03) in the 8-hour urinary
      flurbiprofen recovery ratio after administration of the 6-drug cocktail compared
      with that after administration of flurbiprofen alone. The 6-drug cocktail was
      well tolerated. CONCLUSION: The results of this study show that caffeine
      (CYP1A2), chlorzoxazone (CYP2E1), dapsone (N-acetyltransferase 2), debrisoquin
      (CYP2D6), flurbiprofen (CYP2C9), and mephenytoin (CYP2C19) can be simultaneously
      administered in low doses without metabolic interaction.

PMID- 16952494
TI  - Intravascular tumor necrosis factor alpha blockade reverses endothelial
      dysfunction in rheumatoid arthritis.
AB  - BACKGROUND: Patients with rheumatoid arthritis (RA) have endothelial dysfunction,
      which may predispose them to the risk of premature atherosclerosis. This study
      investigated the involvement of tumor necrosis factor (TNF) alpha in the
      pathophysiologic characteristics of this abnormality by use of the TNF-alpha
      neutralizing antibody infliximab. METHODS: Endothelium-dependent and -independent
      vasodilator responses to intra-arterial infusion of increasing doses of
      acetylcholine and sodium nitroprusside, respectively, were assessed by strain
      gauge plethysmography in patients (n = 10) with early RA during saline solution
      infusion and after intra-arterial infusion of infliximab (200 microg/min).
      RESULTS: Circulating markers of systemic inflammation (C-reactive protein and
      interleukin 6) were higher in patients than in control subjects (n = 10, both P <
      .05), whereas plasma levels of TNF-alpha and soluble TNF receptor types 1 and 2
      were similar in both groups (all P > .05). During saline solution infusion, the
      vasodilator response to acetylcholine was blunted in patients with RA compared
      with control subjects (14.2 +/- 9.2 mL . min-(1). dL-(1) versus 23.7 +/- 9.2 mL .
      min-(1). dL-(1) at the highest dose, P = .004) whereas vasodilation to sodium
      nitroprusside was not different between groups (P = .10). In patients with RA
      infliximab did not modify circulating C-reactive protein levels (P = .29, versus
      saline solution) but did potentiate the vasodilator response to acetylcholine
      (21.0 +/- 11.1 mL . min-(1). dL-(1); P = .004, versus saline solution). The
      response to sodium nitroprusside, in contrast, was not modified by infliximab (P
      = .28 versus saline solution). CONCLUSIONS: Intravascular administration of anti
      TNF-alpha antibody ameliorates endothelial function in patients with RA but does
      not concurrently affect systemic inflammatory changes. Our findings suggest that
      enhanced TNF-alpha generation within the vessel wall, rather than systemic
      mechanisms, plays a role in the pathobiologic features of endothelial dysfunction
      in RA.

PMID- 16952493
TI  - Celecoxib, ibuprofen, and the antiplatelet effect of aspirin in patients with
      osteoarthritis and ischemic heart disease.
AB  - BACKGROUND AND OBJECTIVE: We performed a placebo-controlled, randomized study to
      address whether celecoxib or ibuprofen undermines the functional range of
      inhibition of platelet cyclooxygenase (COX)-1 activity by aspirin in patients
      with osteoarthritis and stable ischemic heart disease. METHODS: Twenty-four
      patients who were undergoing long-term treatment with aspirin (100 mg daily) for
      cardioprotection were coadministered celecoxib, 200 mg twice daily, ibuprofen,
      600 mg 3 times daily, or placebo for 7 days. RESULTS: The coadministration of
      placebo or celecoxib did not undermine the aspirin-related inhibition of platelet
      COX-1 activity, as assessed by measurements of serum thromboxane B(2) (TXB(2))
      levels, as well as platelet function. In contrast, a significant (P < .001)
      increase in serum TXB(2) level was detected on day 7 before drug administration
      (median, 19.13 ng/mL [range, 1-47.5 ng/mL]) and at 24 hours after the
      coadministration of aspirin and ibuprofen (median, 22.28 ng/mL [range, 4.9-44.4
      ng/mL]) versus baseline (median, 1.65 ng/mL [range, 0.55-79.8 ng/mL]); this was
      associated with a significant increase in arachidonic acid-induced platelet
      aggregation (P < .01) and adenosine diphosphate-induced platelet aggregation (P <
      .05) and a decrease in the time to form an occlusive thrombus in the platelet
      function analyzer (P < .01). The urinary excretion of 11-dehydro-TXB(2), an index
      of systemic thromboxane biosynthesis, was not significantly affected by the
      coadministration of treatment drugs. At steady state, a comparable and persistent
      inhibition of lipopolysaccharide-stimulated prostaglandin E(2) generation, a
      marker of COX-2 activity ex vivo, was caused by ibuprofen (>or=80%) or celecoxib
      (>or=70%) but not placebo. CONCLUSIONS: Unlike ibuprofen, celecoxib did not
      interfere with the inhibition of platelet COX-1 activity and function by aspirin
      despite a comparable suppression of COX-2 ex vivo in patients with osteoarthritis
      and stable ischemic heart disease.

PMID- 16952495
TI  - Comprehensive evaluation of variability in nicotine metabolism and CYP2A6
      polymorphic alleles in four ethnic populations.
AB  - Human cytochrome P450 (CYP) 2A6 metabolizes nicotine to cotinine and is a
      possible modulator of nicotine addiction. Quantitative and qualitative
      differences in nicotine addiction have been observed between ethnic groups.
      However, there are few data on the ethnic influences of the CYP2A6-nicotine
      metabolism relationship, particularly with regard to black subjects. We
      determined the nicotine metabolism and CYP2A6 genotype in 176 white subjects and
      160 black subjects, comparing them with our previous data from 209 Korean
      subjects and 92 Japanese subjects. Large interindividual differences were
      observed in the cotinine/nicotine ratios in plasma calculated as an index of
      nicotine metabolism in white subjects (range, 0.6-36.5) and in black subjects
      (range, 0.9-30.4). No ethnic difference in the metabolic ratio was observed among
      white subjects (mean, 7.2 +/- 5.0), black subjects (mean, 7.1 +/- 4.7), and
      Korean subjects (mean, 8.7 +/- 11.9), whereas Japanese subjects showed a
      significantly (P < .005) lower metabolic ratio (mean, 3.8 +/- 3.1) compared with
      the other populations. Women showed significantly (P < .05) higher metabolic
      ratios than men in the black population (8.0 +/- 5.3 versus 6.0 +/- 3.7). Obvious
      ethnic differences in the CYP2A6 alleles were observed among these 4 populations.
      The combined frequencies of the alleles lacking or showing reduced enzymatic
      activity (CYP2A6*2, CYP2A6*4, CYP2A6*5, CYP2A6*7, CYP2A6*9, CYP2A6*10, CYP2A6*11,
      CYP2A6*17, CYP2A6*19, and CYP2A6*20) were 9.1%, 21.9%, 42.9%, and 50.5% in white,
      black, Korean, and Japanese subjects, respectively. These CYP2A6 alleles were
      associated with reduced nicotine metabolism. Among the homozygotes of CYP2A6*1,
      interindividual and ethnic differences in the metabolic ratio were still
      observed. Thus some factors other than genetic ones might also contribute to the
      interindividual and ethnic differences. This comprehensive study of 4 populations
      extends our understanding of nicotine metabolism and the impact of genetic
      polymorphisms of the CYP2A6 gene.

PMID- 16952496
TI  - Is celecoxib an inducer of cytochrome P450 3A4 in subjects carrying the CYP2C9*3
      allele?

PMID- 16952498
TI  - Imaging P-glycoprotein at the human blood-brain barrier.

PMID- 16952500
TI  - Declining estimates of infertility in the United States: 1982-2002.
AB  - OBJECTIVE: To determine if the decline in infertility has been uniform across
      subgroups. DESIGN: Periodic data from the National Fertility Survey and the
      National Survey of Family Growth were used to determine which factors contributed
      to the decline in 12-month infertility in the United States. SETTING: National
      Survey of Family Growth, a periodic US nationally representative study.
      PATIENT(S): A nationally representative sample of married women aged 15-44 years,
      N = 15,303 for pooled data across 4 survey years. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Estimates of infertility prevalence among married women aged
      15-44 years. RESULT(S): The decline in 12-month infertility in the United States
      from 8.5% in 1982 and 7.4% in 2002 was significant. This decline was evident in
      nearly all subgroups of married women. In the multivariate analysis, 12-month
      infertility was more likely among women who were older and nulliparous, were non
      Hispanic black or Hispanic, and did not have a college degree. The decline in 12
      month infertility was observed even after controlling for the compositional
      differences of the population over time. CONCLUSION(S): Among married women in
      the United States, there has been a significant decline in 12-month infertility,
      which cannot be explained by changes in the composition of the population from
      1982-2002.

PMID- 16952501
TI  - The decline of infertility: apparent or real?
AB  - Data on trends in fertility and infertility are of significant interest, because
      they may reflect social, behavioral, biological, or environmental changes. The
      conclusion that infertility has declined in the United States, based on data from
      the National Survey of Family Growth, must be interpreted with great caution
      because of definitional and methodologic concerns.

PMID- 16952502
TI  - The challenge and enjoyment of the interpretation of epidemiologic data.
AB  - The trend toward a decline in the percentage of women with infertility in the
      United States appears real. While the factors associated with this trend are
      likely many, complex, and interrelated, we cannot overlook the positive impact of
      those individuals who practice in the field of reproductive medicine.

PMID- 16952503
TI  - Estimating infertility: the devil is in the details.
AB  - Self-reported data have serious limitations, particularly when the outcome is
      constructed from indirect questions. Policy decisions require clearly defined
      issues, validated tools, careful and comprehensive analysis, and cautious
      interpretation.

PMID- 16952504
TI  - Impact of subgroup analysis on estimates of infertility.
AB  - Conclusions regarding estimates of infertility may reflect study bias based on
      the definition of infertility used. Careful consideration of how the infertile
      population is defined, as well its use in subgroup analysis that may not be
      generalizable to the population of infertile women as a whole, is needed.

PMID- 16952506
TI  - No difference in cycle pregnancy rate and in cumulative live-birth rate between
      women with surgically treated minimal to mild endometriosis and women with
      unexplained infertility after controlled ovarian hyperstimulation and
      intrauterine insemination.
AB  - OBJECTIVE: The association between infertility and minimal to mild endometriosis
      is controversial and poorly understood. The clinical pregnancy rate (PR) per
      cycle after controlled ovarian hyperstimulation (COH) with or without
      intrauterine insemination (IUI) is reportedly lower in women with surgically
      untreated minimal to mild endometriosis than in women with unexplained
      infertility. It is possible that prior laparoscopic removal of endometriosis has
      a positive effect on the clinical PR after COH and IUI. Therefore, we tested the
      hypothesis that after COH and IUI the PR per cycle and the cumulative live-birth
      rate (CLBR) are equal or higher in women with recently surgically treated minimal
      to mild endometriosis when compared with women with unexplained infertility.
      DESIGN: A retrospective, controlled cohort study. SETTING: Leuven University
      Fertility Centre, a tertiary academic referral center. PATIENT(S): One hundred
      seven women treated during 259 cycles with COH and IUI including patients with
      endometriosis (n = 58, 137 cycles) and unexplained infertility (n = 49, 122
      cycles). All patients with endometriosis had minimal (n = 41, 100 cycles) or mild
      (n = 17, 37 cycles) disease that had been laparoscopically removed within 7
      months before the onset of treatment with COH and IUI. INTERVENTION(S):
      Controlled ovarian hyperstimulation using clomiphene citrate (23 cycles) or
      gonadotrophins (236 cycles) in combination with IUI. MAIN OUTCOME MEASURE(S):
      Clinical PR per cycle and CLBR within four cycles of treatment with COH and IUI.
      RESULT(S): The clinical PR per cycle was comparable in women with minimal or mild
      endometriosis (21% or 18.9%, respectively) and in women with unexplained
      infertility (20.5%). The CLBR within four cycles of COH and IUI was also
      comparable in women with minimal endometriosis, mild endometriosis, and
      unexplained infertility (70.2%, 68.2 %, 66.5%, respectively). CONCLUSION(S): The
      data from our study suggest that COH and IUI shortly after laparoscopic excision
      of endometriosis is as effective as COH and IUI in patients with unexplained
      subfertility.

PMID- 16952507
TI  - Effect of cryopreservation on sperm apoptotic deoxyribonucleic acid fragmentation
      in patients with oligozoospermia.
AB  - OBJECTIVE: To verify if the increase in sperm apoptotic DNA fragmentation during
      cryopreservation is greater in oligozoospermic patients than in normozoospermic
      controls. DESIGN: Controlled prospective study. SETTING: Patients in an academic
      research environment. PATIENT(S): Forty-seven patients with oligozoospermia
      (concentration <10 x 10(6) sperm/mL) and 30 normozoospermic men. INTERVENTION(S):
      Sperm cryopreservation using a standard protocol with a test-yolk buffer,
      glycerol as the cryoprotectant. MAIN OUTCOME MEASURE(S): Rate of apoptotic sperm
      DNA fragmentation as assessed by the terminal deoxynucleotidyl-mediated
      deoxyuridine triphosphate nickend labeling (TUNEL) assay, graded in apoptotic or
      nonapoptotic, before and after cryopreservation. RESULT(S): An increase in
      apoptotic DNA fragmentation was observed in all the groups, regardless of sperm
      concentration. Normozoospermic men presented a smaller rate of apoptotic DNA
      fragmentation than oligozoospermic patients, both in pre- and
      postcryopreservation samples. The increase in DNA fragmentation was similar in
      both groups. CONCLUSION(S): Cryopreservation induces apoptotic sperm DNA
      fragmentation in men, regardless of sperm concentration. Men with oligozoospermia
      present with higher precryopreservation and postcryopreservation apoptotic sperm
      DNA fragmentation. The increase in DNA fragmentation is similar in both groups.

PMID- 16952508
TI  - Embryos generated using testicular spermatozoa have higher developmental
      potential than those obtained using epididymal spermatozoa in men with
      obstructive azoospermia.
AB  - OBJECTIVE: To determine whether the injection of testicular spermatozoa results
      in more viable embryos (higher implantation rate) than injection of epididymal
      spermatozoa in cases of obstructive azoospermia. DESIGN: Retrospective analysis
      of 265 cases of testicular sperm aspiration (TESA) and percutaneous sperm
      aspiration (PESA), including 185 cases of obstructive azoospermia. SETTING:
      Private Infertility clinic. PATIENT(S): None, charts review. INTERVENTION(S):
      None, charts review. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate (PR),
      implantation rate. RESULT(S): Although fertilization rates were higher in the
      PESA group, implantation rates were significantly better in the TESA group. There
      was also a trend to higher ongoing PR and lower miscarriage rates in TESA cases.
      CONCLUSION(S): In cases of obstructive azoospermia, embryos generated using
      testicular spermatozoa have higher developmental potential than those obtained
      using epididymal spermatozoa.

PMID- 16952509
TI  - Altered expression pattern of heat shock transcription factor, Y chromosome
      (HSFY) may be related to altered differentiation of spermatogenic cells in testes
      with deteriorated spermatogenesis.
AB  - OBJECTIVE: To evaluate the expression patterns of heat shock transcription
      factor, Y chromosome (HSFY), in the testes showing deteriorated spermatogenesis.
      DESIGN: Prospective study. SETTING: University hospital, its branch hospital, and
      academic laboratory. PATIENT(S): Men undergoing testicular biopsy for the
      investigation of infertility and men undergoing orchiectomy for testicular
      cancer. INTERVENTION(S): After pathologic evaluation, specimens were subdivided
      into three groups: normal spermatogenesis (n = 8), maturation arrest (n = 5), and
      Sertoli cell-only syndrome (n = 4). Immunostaining and Western blotting
      techniques determined the expression of HSFY. MAIN OUTCOME MEASURE(S): Expression
      of HSFY in testes. RESULT(S): Western blotting data revealed HSFY in the
      testicular tissues with normal spermatogenesis, maturation arrest, and Sertoli
      cell-only syndrome, but the amount of the protein in the maturation arrest and
      Sertoli cell-only syndrome samples was altered. The immunohistochemical data
      demonstrated that HSFY was expressed in spermatogenic cells and Sertoli cells in
      all specimens. However, the expression of HSFY was low or absent in spermatogenic
      cells of maturation arrest specimens, and the ratio of HSFY expressed in Sertoli
      cells was different in the specimens with maturation arrest and with Sertoli cell
      only syndrome. CONCLUSION(S): Altered expression of the HSFY in the testis
      showing deteriorated spermatogenesis may be associated with alteration of
      spermatogenic cell differentiation.

PMID- 16952510
TI  - Analysis of protein expression (secretome) by human and mouse preimplantation
      embryos.
AB  - OBJECTIVE: To analyze the protein production into the surrounding medium
      (secretome) of both human and mouse embryos and correlate these findings with
      ongoing blastocyst development. Along with improvements in culture systems, there
      is renewed focus on the development of noninvasive viability assays in human IVF.
      Because the majority of biologic functions are carried out by proteins, it is
      important to study the dynamics of the proteome during embryonic development and
      its response to both internal and external stimuli. DESIGN: Experimental study.
      SETTING: Research laboratory. PATIENT(S): Couples undergoing infertility
      treatment donated with consent spent culture media for research. INTERVENTION(S):
      Analysis by time-of-flight mass spectrometry. MAIN OUTCOME MEASURE(S): Protein
      profiles of spent culture media. RESULT(S): Distinctive and significantly
      different secretome profiles were observed at each embryonic developmental stage
      (P<0.05). Correlation of day 5 secretome data with ongoing blastocyst development
      revealed an 8.5-kDa protein biomarker that was significantly up-regulated
      (P<0.05). The best candidate for this protein biomarker was ubiquitin, which has
      been implicated in the implantation process of mammalian species. CONCLUSION(S):
      This approach to analyze the secretome should not only further our understanding
      of embryo physiology but provide the basis for the development of noninvasive
      assays of embryo viability in human IVF.

PMID- 16952511
TI  - A randomized controlled pilot study of acupuncture for postmenopausal hot
      flashes: effect on nocturnal hot flashes and sleep quality.
AB  - OBJECTIVE: To assess the effectiveness of acupuncture on postmenopausal nocturnal
      hot flashes and sleep. DESIGN: Prospective randomized placebo-controlled study.
      SETTING: Stanford University School of Medicine and private acupuncture offices.
      INTERVENTION(S): Active or placebo acupuncture was administered for nine sessions
      over seven weeks. MAIN OUTCOME MEASURE(S): Severity and frequency of nocturnal
      hot flashes from daily diaries and Pittsburgh Sleep Quality Index (PSQI).
      PATIENT(S): Twenty-nine postmenopausal women experiencing at least seven moderate
      to severe hot flashes daily, with E(2) <18 pg/mL and FSH 30.0-110.0 IU/L.
      RESULT(S): Nocturnal hot-flash severity significantly decreased in the active
      acupuncture group (28%) compared with the placebo group (6%), P=.017. The
      frequency of nocturnal hot flashes also decreased in the active group (47%,
      P=.001), though it was not significantly different from the placebo group (24%,
      P=.170; effect size = 0.65). Treatment did not differentially influence sleep;
      however, correlations between improvements in PSQI and reductions in nocturnal
      hot flash severity and frequency were significant (P<.026). CONCLUSION(S):
      Acupuncture significantly reduced the severity of nocturnal hot flashes compared
      with placebo. Given the strength of correlations between improvements in sleep
      and reductions in nocturnal hot flashes, further exploration is merited.

PMID- 16952512
TI  - Tail stump syndrome associated with chromosomal translocation in two brothers
      attempting intracytoplasmic sperm injection.
AB  - OBJECTIVE: To raise the possibility that a familial chromosomal translocation
      associated with teratozoospermia can disrupt a gene necessary for flagellum
      assembly. DESIGN: Case report. SETTING: University hospital. PATIENT(S): Two
      brothers with infertility related to anomalies of meiotic division and of the
      flagella assembly, presenting the same balanced 5-12 autosomal translocation.
      INTERVENTION(S): Several intracytoplasmic sperm injection (ICSI) cycles in our
      IVF department for both couples. MAIN OUTCOME MEASURE(S): Sperm analysis,
      karyotypes, electron microscopy, and fluorescence in situ hybridization (FISH)
      analysis of spermatozoa performed using probes coding for chromosomes X, Y, 13,
      18, and 21. RESULT(S): In both brothers, sperm analysis indicated a tail stump
      syndrome. Electron microscopy analysis displayed complex abnormalities, which
      were probably related to meiotic errors. The FISH analysis indicated an increase
      of diploid germ cells. Karyotypes of both patients revealed the same balanced
      chromosomal t(5;12) (p15.1; q21) translocation. Results of ICSI cycles were
      comparable for both couples. A twin pregnancy was achieved in one of these two
      couples, but a spontaneous miscarriage occurred at 10 weeks of gestation.
      CONCLUSION(S): The flagella anomalies raise the possibility that the
      translocation disrupts a gene necessary for the flagellum assembly, although a
      mutation in a gene unrelated to the chromosome breakpoints cannot be excluded.

PMID- 16952513
TI  - Effectiveness of treating ovarian hyperstimulation syndrome with cabergoline in
      two patients with gonadotropin-producing pituitary adenomas.
AB  - OBJECTIVE: To report the effect of cabergoline on ovarian hyperstimulation
      syndrome associated with gonadotropin-secreting pituitary adenomas. DESIGN: Case
      report. SETTING: Outpatient practice. PATIENT(S): Two women with menstrual
      irregularity, enlarged ovaries, high E(2), and normal gonadotropin levels.
      INTERVENTION(S): Cabergoline treatment and transsphenoidal surgery. MAIN OUTCOME
      MEASURE(S): Estradiol levels, transvaginal ultrasonography, and pituitary
      magnetic resonance imaging. Transsphenoidal surgery showed pituitary adenoma
      staining for LH in both patients. RESULT(S): Cabergoline was effective in
      reducing E(2) levels and decreasing ovarian size but ineffective in shrinking the
      pituitary adenomas. CONCLUSION(S): This is the first description of the
      effectiveness of cabergoline as the primary treatment of spontaneous ovarian
      hyperstimulation syndrome in patients with gonadotropin-producing pituitary
      adenomas.

PMID- 16952514
TI  - Reciprocal translocation t(7;16)(q21.2;p13.3) in an infertile man.
AB  - OBJECTIVE: To report the first case of reciprocal translocation
      t(7;16)(q21.2;p13.3) associated with male factor infertility. DESIGN: Case
      report. SETTING: University genetics laboratory and university andrology unit.
      PATIENT(S): A 38-year-old man with infertility and oligoasthenoteratozoospermia,
      but otherwise healthy. INTERVENTION(S): Chromosome analyses from peripheral blood
      lymphocyte cultures using Giemsa (G)-banding (GTG) and C-banding (CBG) and
      fluorescent in situ hybridization (FISH) were performed. MAIN OUTCOME MEASURE(S):
      Sperm count, motility, morphology, GTG and CBG banding, and FISH. RESULT(S): We
      report an apparently unique reciprocal translocation t(7;16)(q21.2;p13.3)
      confirmed by FISH in an infertile man. Semen analyses showed
      oligoasthenoteratozoospermia, with sperm count ranging from 2 x 10(6)/mL to 5 x
      10(6)/mL and head defects (98%) in sperm morphology. CONCLUSION(S): In the
      present patient the breakpoint at 16p13.3 could have disrupted or harbored the
      PRM1, PRM2, or TNP2 genes responsible for the replacement of the histones
      involved in packaging the DNA into the sperm head. Resulting haploinsufficiency
      of these genes is likely to be the cause of sperm head defects and infertility in
      the patient. This case supports the opinion that alterations in the expression of
      protamine genes may be one of the causes of male factor infertility.

PMID- 16952515
TI  - Hematuria and clot retention after transvaginal oocyte aspiration: a case report.
AB  - OBJECTIVE: To report a case of bladder injury with hematuria and urinary
      retention after transvaginal oocyte aspiration. DESIGN: Case report. SETTING:
      Emergency room in a university medical center. PATIENT(S): A 28-year-old woman
      presented with urinary retention and suprapubic pain 8 hours after oocyte
      aspiration. INTERVENTION(S): Foley catheter, intravenous fluid bolus, bladder
      irrigation, and computed tomography with postvoid films that showed a blood clot
      in the bladder. Patient was discharged home with antibiotics and catheter in
      place. MAIN OUTCOME MEASURE(S): Clinical follow-up. RESULT(S): Patient passed
      voiding trial 4 days later and was artificially inseminated. No further hematuria
      or voiding problems were reported, and she had a successful pregnancy.
      CONCLUSION(S): Patients who elect to undergo oocyte aspiration should be warned
      about the possibility of bladder injury because of the close proximity of the
      ovaries to the bladder, and physicians should have an appropriate treatment plan.

PMID- 16952516
TI  - Different perceptions of similar observations.

PMID- 16952518
TI  - Predictive value of myomectomy.

PMID- 16952520
TI  - Registries for anti-adhesion products?

PMID- 16952522
TI  - Dissecting and temporarily resuspending the adherent ovary.

PMID- 16952525
TI  - Solutions to the problem of multiple pregnancy with IVF.

PMID- 16952526
TI  - Reanalysis of the data--science at its best and always informative.

PMID- 16952528
TI  - The future of sperm-derived mRNAs.

PMID- 16952530
TI  - Poor response--the devil is in the definition.

PMID- 16952537
TI  - The future of physician-scientists-demise or opportunity?

PMID- 16952538
TI  - Advances in endoscopic imaging of Barrett's esophagus.

PMID- 16952539
TI  - Endoscopic full-thickness plication for the treatment of gastroesophageal reflux
      disease: A randomized, sham-controlled trial.
AB  - BACKGROUND & AIMS: The aim of this study was to determine the effectiveness of
      endoscopic full-thickness plication for the treatment of gastroesophageal reflux
      disease (GERD) in comparison with a sham procedure. METHODS: Patients with
      symptomatic GERD requiring maintenance proton pump inhibitor (PPI) therapy were
      entered into a randomized, single-blind, prospective, multicenter trial. Seventy
      eight patients were randomly assigned to undergo endoscopic full-thickness
      restructuring of the gastric cardia with transmural suture. Eighty-one patients
      underwent a sham procedure. Group assignments were revealed following the 3-month
      evaluation. The primary end point was > or =50% improvement in GERD health
      related quality of life (HRQL) score. Secondary end points included medication
      use and esophageal acid exposure. RESULTS: By intention-to-treat analysis, at 3
      months, the proportion of patients achieving > or =50% improvement in GERD-HRQL
      score was significantly greater in the active group (56%) compared with the sham
      group (18.5%; P < .001). Complete cessation of PPI therapy was higher among
      patients in the active group than in the sham group by intention-to-treat
      analysis (50% vs 24%; P = .002). The percent reduction in median percent time pH
      < 4 was significantly improved within the active group versus baseline (7 vs 10,
      18%, P < .001) but not in the sham group (10 vs 9, -3%, P = .686). Between-group
      analysis revealed the active therapy to be superior to the sham in improving
      median percent time pH < 4 (P = .010). There were no perforations or deaths.
      CONCLUSIONS: Endoscopic full-thickness plication more effectively reduces GERD
      symptoms, PPI use, and esophageal acid exposure than a sham procedure.

PMID- 16952540
TI  - Ground-glass, polyglucosan-like hepatocellular inclusions: A "new" diagnostic
      entity.
AB  - BACKGROUND & AIMS: Ground-glass (GG) inclusions within hepatocytes are an
      important histopathologic marker of chronic hepatitis B virus (HBV) infection but
      may also be seen in Lafora's disease (myoclonus epilepsy), cyanamide alcohol
      aversion therapy, and type IV glycogenosis. We have noted a recent increased
      incidence of liver biopsy and postmortem specimens with GG inclusions associated
      with none of these etiologic factors. This study was undertaken to further
      delineate the clinical and liver pathologic features in such cases and their
      possible pathogenesis. METHODS: Ten cases with GG inclusions (8 biopsy, 2
      postmortem) were examined by light and electron microscopy, and the patients'
      clinical records were reviewed. RESULTS: Light microscopy demonstrated pale pink,
      oval to crescentic intracytoplasmic inclusions with a predilection for periportal
      hepatocytes but sometimes present throughout the lobules. The inclusions were
      intensely positive on periodic acid-Schiff stain and digested with diastase.
      Transmission electron microscopy of two cases showed non-membrane-bound
      cytoplasmic collections of granules with mild-to-moderate electron density,
      consistent with abnormal glycogen granules. The patients included 7 transplant
      recipients (liver, hematopoietic stem cell), 3 with type 2 diabetes and a child
      on chronic parenteral nutrition for short bowel syndrome. Medications included
      immunosuppressive agents, antibiotics, and insulin. CONCLUSIONS: GG
      hepatocellular inclusions may be seen in individuals without HBV infection or
      other recognized etiologies, appear to be composed of abnormal glycogen and
      closely resemble polyglucosan bodies described in humans, animals, and
      experimental models. The possible pathogenetic roles of disturbed glycogen
      metabolism and polypharmacotherapy are stressed.

PMID- 16952541
TI  - Cost analysis and cost determinants in a European inflammatory bowel disease
      inception cohort with 10 years of follow-up evaluation.
AB  - BACKGROUND & AIMS: Economic analysis in chronic diseases is a prerequisite for
      planning a proper distribution of health care resources. We aimed to determine
      the cost of inflammatory bowel disease, a lifetime illness with considerable
      morbidity. METHODS: We studied 1321 patients from an inception cohort in 8
      European countries and Israel over 10 years. Data on consumption of resources
      were obtained retrospectively. The cost of health care was calculated from the
      use of resources and their median prices. Data were analyzed using regression
      models based on the generalized estimating equations approach. RESULTS: The mean
      annual total expenditure on health care was 1871 Euro/patient-year for
      inflammatory bowel disease, 1524 Euro/patient-year for ulcerative colitis, and
      2548 Euro/patient-year for Crohn's disease (P < .001). The most expensive
      resources were medical and surgical hospitalizations, together accounting for 63%
      of the cost in Crohn's disease and 45% in ulcerative colitis. Total and
      hospitalization costs were much higher in the first year after diagnosis than in
      subsequent years. Differences in medical and surgical hospitalizations were the
      primary cause of substantial intercountry variations of cost; the mean cost of
      health care was 3705 Euro/patient-year in Denmark and 888 Euro/patient-year in
      Norway. The outlay for mesalamine, a costly medication with extensive use, was
      greater than for all other drugs combined. Patient age at diagnosis and sex did
      not affect costs. CONCLUSIONS: In this multinational, population-based, time
      dependent characterization of the health care cost of inflammatory bowel disease,
      increased expenditure was driven largely by country, diagnosis, hospitalization,
      and follow-up year.

PMID- 16952543
TI  - A randomized, controlled trial of transanal irrigation versus conservative bowel
      management in spinal cord-injured patients.
AB  - BACKGROUND & AIMS: Bowel dysfunction in patients with spinal cord injury often
      causes constipation, fecal incontinence, or a combination of both with a
      significant impact on quality of life. Transanal irrigation improves bowel
      function in selected patients. However, controlled trials of different bowel
      management regimens are lacking. The aim of the present study was to compare
      transanal irrigation with conservative bowel management (best supportive bowel
      care without irrigation). METHODS: In a prospective, randomized, controlled,
      multicenter trial involving 5 specialized European spinal cord injury centers, 87
      patients with spinal cord injury with neurogenic bowel dysfunction were randomly
      assigned to either transanal irrigation (42 patients) or conservative bowel
      management (45 patients) for a 10-week trial period. RESULTS: Comparing transanal
      irrigation with conservative bowel management at termination of the study, the
      mean (SD) scores were as follows: Cleveland Clinic constipation scoring system
      (range, 0-30, 30 = severe symptoms) was 10.3 (4.4) versus 13.2 (3.4) (P = .0016),
      St. Mark's fecal incontinence grading system (range, 0-24, 24 = severe symptoms)
      was 5.0 (4.6) versus 7.3 (4.0) (P = .015), and the Neurogenic Bowel Dysfunction
      Score (range, 0-47, 47 = severe symptoms) was 10.4 (6.8) versus 13.3 (6.4) (P =
      .048). The modified American Society of Colorectal Surgeon fecal incontinence
      scores (for each subscale, range is 0-4, 4 = high quality of life) were:
      lifestyle 3.0 (0.7) versus 2.8 (0.8) (P = .13), coping/behavior 2.8 (0.8) versus
      2.4 (0.7) (P = .013), depression/self perception 3.0 (0.8) versus 2.7 (0.8) (P =
      .055), and embarrassment 3.2 (0.8) versus 2.8 (0.9) (P = .024). CONCLUSIONS:
      Compared with conservative bowel management, transanal irrigation improves
      constipation, fecal incontinence, and symptom-related quality of life.

PMID- 16952542
TI  - Prognostic impact of microsatellite instability and DNA ploidy in human colon
      carcinoma patients.
AB  - BACKGROUND & AIMS: Genomic instability in colon cancers is a consequence of
      chromosomal instability characterized by aneuploidy or defective DNA mismatch
      repair (MMR) indicated by microsatellite instability (MSI). Given that high
      frequency MSI (MSI-H) and diploidy are correlated, we determined whether they are
      independent prognostic variables. METHODS: Astler-Coller stage B2 and C colon
      cancers (N = 528) from patients treated in 5-fluorouracil-based adjuvant therapy
      trials were analyzed for MSI using 11 microsatellite markers. Immunostaining for
      hMLH1, hMSH2, and p53 proteins was performed. DNA ploidy was analyzed by flow
      cytometry. Associations with disease-free and overall survival were determined.
      RESULTS: MSI-H was detected in 95 tumors (18%), and 70 (74%) of these were
      diploid. Tumors showing MSI-H (hazard ratio, 0.65; 95% confidence interval, 0.44
      0.96; P = .023) or loss of MMR proteins (P = .024) were associated with better
      overall survival. Improved disease-free and overall survival were found for
      diploid versus aneuploid/tetraploid tumors (overall survival: hazard ratio, 0.59;
      95% confidence interval, 0.43-0.79; P = .0003). In the subgroups of MSI-H and
      microsatellite stable (MSS)/low-frequency MSI (MSI-L) tumors, diploidy was
      associated with better survival. The prognostic impact of ploidy was similar in
      stage B2 and C tumors. Ploidy did not predict the benefit of 5-fluorouracil-based
      treatment. When ploidy, MSI, and MMR proteins were analyzed in the same
      multivariate model, only ploidy remained significant. CONCLUSIONS: DNA ploidy and
      MSI-H status were independent prognostic variables, yet ploidy was the strongest
      marker. Diploidy was associated with better survival in MSI-H and in MSS/MSI-L
      patient subgroups.

PMID- 16952544
TI  - Excess IL-12 but not IL-23 accompanies the inflammatory bowel disease associated
      with common variable immunodeficiency.
AB  - BACKGROUND & AIMS: Common variable immunodeficiency (CVID) patients can develop
      an idiopathic inflammatory bowel disease resulting in chronic diarrhea and life
      threatening malabsorption. This study was designed to assess the status of the
      gastrointestinal tract and to define the mucosal immune abnormalities in patients
      with and without symptomatic gut inflammatory disease. METHODS: CVID patients
      underwent tests of gut absorption, peripheral blood mononuclear cell phenotyping,
      and upper and lower endoscopy for histology and lamina propria mononuclear cell
      (LPMC) cytokine production. RESULTS: CVID patients with gastrointestinal symptoms
      differed from asymptomatic CVID patients by having significantly longer duration
      of disease and lower body mass index, D-xylose absorption, serum albumin,
      CD4/CD45RA cells, CD3/CD25 cells, and natural killer cells. Symptomatic CVID
      patients showed diffuse histologic inflammatory changes in the duodenal and
      colonic mucosa including villus blunting, increased lamina propria and
      intraepithelial lymphocytes, and epithelial apoptosis, less frequently seen in
      asymptomatic patients. LPMCs from symptomatic CVID patients produced
      significantly higher T-helper (Th) 1 cytokines, interleukin-12, and interferon
      gamma. Compared with the Th1 cytokines produced by LPMCs from Crohn's disease,
      CVID patients did not produce excess amounts of interleukin-23, interleukin-17,
      or tumor necrosis factor-alpha. CONCLUSIONS: The idiopathic inflammatory bowel
      disease associated with gastrointestinal symptoms in CVID is a unique combination
      of diverse histologic findings accompanied by excessive Th1 cytokine production,
      distinct from that in Crohn's disease. These data show that human gut mucosal
      inflammatory disease can occur with excess interleukin-12 and interferon-gamma
      production alone and provide a rationale for developing targeted therapies for
      this complication of CVID.

PMID- 16952545
TI  - Hemophilic siblings with chronic hepatitis C: Familial aggregation of spontaneous
      and treatment-related viral clearance.
AB  - BACKGROUND & AIMS: Hemophilic siblings provide a unique population to explore the
      natural history of chronic hepatitis C. METHODS: From 3993 hemophilic patients
      with hepatitis C, 257 sibling pairs, of which both members had evidence of
      hepatitis C infection, were studied to evaluate the genetic contribution to
      spontaneous and treatment-induced clearance of hepatitis C infection and
      progression of liver disease. Familial aggregation was assessed by comparing
      observed probabilities of concordance for these disease characteristics within
      sibling pairs to those expected for randomly paired hemophilic subjects.
      Additional measures of familial aggregation, heritability, and sibling relative
      risk were also calculated. RESULTS: Among human immunodeficiency virus-negative
      subjects, concordance for spontaneous viral clearance was 2-fold higher in
      siblings compared with randomly paired subjects (8.8% vs 4.3%, respectively, P =
      .04). Similarly, the concordance rate for treatment-related viral clearance was
      over twice that among sibling pairs than among randomly paired hemophiliacs
      (31.3% vs 13.3%, respectively, P = ns). Heritability estimates for spontaneous
      and treatment-induced viral clearance were 0.24 +/- 0.14 (P = .04) and 0.43 +/-
      0.42 (P = .10), respectively. The sibling relative risks for these respective
      characteristics were 1.6 and 1.7. Concordance for advanced liver disease was
      higher among siblings but did not reach statistical significance (4.0% vs 2.3%,
      respectively, P = ns). The heritability estimate was 0.29 +/- 0.13 (P = .02).
      CONCLUSIONS: Concordance rates and heritability estimates for spontaneous and
      treatment-related viral clearance indicate that genetic factors have a modest
      influence on the outcome of hepatitis C, although shared environmental factors
      cannot be excluded. Investigations to map candidate disease-susceptibility genes
      associated with these characteristics must be approached with caution.

PMID- 16952546
TI  - Functional analysis of complex hepatitis B virus variants associated with
      development of liver cirrhosis.
AB  - BACKGROUND & AIMS: Development of cirrhosis in renal transplant recipients with
      chronic hepatitis B is associated with the accumulation of complex hepatitis B
      virus (HBV) variants carrying deletions in the C gene and/or preS region and
      deletions/insertions in the core promoter. Here, we characterized for the first
      time the phenotype of these complex HBV variants. METHODS: Representative full
      length genomes of the HBV variants that were isolated and cloned from serum and
      liver of an immunosuppressed renal transplant recipient before and during end
      stage liver disease were transfected into the human hepatoma cell line HuH7 and
      functionally analyzed. RESULTS: The variant genomes showed considerably reduced
      levels of precore and surface messenger RNA (mRNA) and of the major spliced
      pregenomic RNA, an increased level of pregenomic RNA, and a partial or complete
      defect in hepatitis B e antigen, core, and surface protein expression/secretion.
      Very low amounts of variant core protein with internal deletion were detectable.
      Reduced hepatitis B surface antigen secretion of some variants correlated with
      aberrant localization of surface proteins in endoplasmic reticulum. Despite the
      defects in viral protein expression, enhanced replication and enrichment in
      competition to wild-type HBV were observed. Enhanced reverse transcription and
      possibly increased levels of pregenomic RNA seem to be responsible for this
      effect. CONCLUSIONS: Development of cirrhosis is associated with accumulation of
      complex variants, which exhibit a drastically altered phenotype combining
      enhanced replication with defects in protein expression. This phenotype appears
      to be based on the major mutations in the core promoter and C gene but is
      considerably influenced by additional mutations throughout the genome.

PMID- 16952547
TI  - Polymorphisms in the steroid and xenobiotic receptor gene influence survival in
      primary sclerosing cholangitis.
AB  - BACKGROUND & AIMS: The steroid and xenobiotic receptor (SXR) is a ligand
      dependent transcription factor that mediates protection against bile acid-induced
      liver injury in cholestatic animal models. Ursodeoxycholic acid and rifampicin
      are known ligands. We investigated whether functional polymorphisms of the SXR
      gene influence disease susceptibility or disease progression in patients with
      primary sclerosing cholangitis (PSC). METHODS: Polymorphisms at 8 loci across the
      SXR gene were genotyped in 327 Scandinavian PSC patients and 275 healthy
      controls. Kaplan-Meier survival analyses and Cox regressions were performed to
      estimate effects from genotypes on patient survival, defined as time from
      diagnostic cholangiography to death or liver transplantation. RESULTS:
      Susceptibility to PSC was not associated with any of the SXR polymorphisms
      studied. Median survival was significantly reduced in patients homozygous for the
      minor allele as compared with patients carrying at least 1 major allele of the
      neighboring polymorphisms rs6785049 (10.8 vs 14.0 years, respectively, P = .01),
      rs1054190 (3.6 vs 13.6 years, respectively, P = .004), and rs3814058 (3.5 vs 13.3
      years, respectively, P = .01). The increased risk of death or liver
      transplantation was confirmed in univariate Cox regressions (relative risk
      [RR](rs6785049) = 1.7, 95% CI: 1.1-2.6; RR(rs1054190) = 3.1, 95% CI: 1.4-7.1; and
      RR(rs3814058) = 2.2, 95% CI: 1.2-4.2 for the 3 polymorphisms, respectively). In
      multiple Cox regressions including age at PSC onset, rs1054190 remained an
      independent risk factor. CONCLUSIONS: Functional SXR gene variants appear to
      modify disease course in PSC. Further investigations of polymorphisms in the SXR
      gene may provide insight into the prognostic importance of SXR-regulated pathways
      in this disease, perhaps even in a therapeutic perspective.

PMID- 16952548
TI  - Increased adipose tissue expression of hepcidin in severe obesity is independent
      from diabetes and NASH.
AB  - BACKGROUNDS & AIMS: Hepcidin is an acute-phase response peptide. We have
      investigated the possible involvement of hepcidin in massive obesity, a state of
      chronic low-grade inflammation. Three groups of severely obese patients with or
      without diabetes or nonalcoholic steatohepatitis were investigated. METHODS:
      Hepcidin expression was studied in liver and adipose tissue of these patients.
      Hepcidin regulation was investigated in vitro by adipose tissue explant
      stimulation studies. RESULTS: Hepcidin was expressed not only in the liver but
      also at the messenger RNA (mRNA) and the protein levels in adipose tissue.
      Moreover, mRNA expression was increased in adipose tissue of obese patients. The
      presence of diabetes or NASH did not modify the hepcidin expression levels in
      liver and adipose tissue. In adipose tissue, mRNA expression correlated with
      indexes of inflammation, interleukin-6, and C-reactive protein. Interleukin-6
      also promoted in vitro hepcidin expression. A low transferrin saturation ratio
      was observed in 68% of the obese patients; moreover, 24% of these patients
      presented with anemia. The observed changes in iron status could be due to the
      role of hepcidin as a negative regulator of intestinal iron absorption and
      macrophage iron efflux. Interestingly, a feedback control mechanism on hepcidin
      expression related to low transferrin saturation occurred in the liver but not in
      the adipose tissue. CONCLUSIONS: Hepcidin is a proinflammatory adipokine and may
      play an important role in hypoferremia of inflammation in obese condition.

PMID- 16952549
TI  - A genome-wide search identifies epigenetic silencing of somatostatin, tachykinin
      1, and 5 other genes in colon cancer.
AB  - BACKGROUND & AIMS: Gene silencing via promoter hypermethylation is a central
      event in the pathogenesis of cancers. To identify novel methylation targets in
      colon cancer, we conducted a genome-wide, microarray-based, in silico, and
      epigenetic search. METHODS: Complementary DNA microarray experiments were first
      performed to identify genes down-regulated in primary colon cancers and up
      regulated in colon cancer cell lines after global DNA demethylation by 5-aza-2'
      deoxycitidine. Candidate methylation targets were then identified by combining
      these microarray data with in silico genetic and functional searches. Candidate
      genes recognized by these searches were further investigated for promoter
      hypermethylation in colon cancer using methylation-specific polymerase chain
      reaction. RESULTS: We identified 51 novel and 3 known candidate methylation
      targets. Subsequent epigenetic analysis revealed that primary colon cancers
      demonstrated frequent methylation of somatostatin (SST, 30 of 34 cases, 88%) and
      the substance P precursor gene tachykinin-1 (TAC1; 16 of 34 cases, 47%). TAC1
      methylation intensity was significantly higher in Dukes A/B than in Dukes C/D
      cancers (P = .01). SST methylation intensity was significantly higher in low
      level microsatellite instability (MSI-L) than in non-MSI-L cancers (P = .02).
      Methylation was associated with messenger RNA down-regulation for both SST and
      TAC1. Furthermore, we isolated 5 additional novel promoter methylation targets:
      NELL1, AKAP12, caveolin-1, endoglin, and MAL. CONCLUSIONS: These data strongly
      suggest that SST and TAC1 are involved in colon carcinogenesis. Further studies
      are now indicated to elucidate mechanisms underlying their involvement in colon
      cancer and their values as clinical biomarkers. NELL1, AKAP12, caveolin-1,
      endoglin, and MAL are also promising tumor suppressor gene candidates deserving
      of further study.

PMID- 16952550
TI  - Effects of mouse and human lipocalin homologues 24p3/lcn2 and neutrophil
      gelatinase-associated lipocalin on gastrointestinal mucosal integrity and repair.
AB  - BACKGROUND & AIMS: The lipocalin superfamily, including the mouse and human
      homologues 24p3/lcn2 and neutrophil gelatinase-associated lipocalin, show great
      functional diversity including roles in olfaction, transportation, and
      prostaglandin synthesis in mammals. Their potential role in maintaining
      gastrointestinal mucosal integrity and repair is, however, unclear. METHODS:
      Changes in 24p3/lcn2 expression in the mouse gut in response to various noxious
      agents were examined using Northern blot, in situ hybridization, and
      immunohistochemistry. Effects of recombinant 24p3/lcn2 on proliferation ([3H]
      thymidine uptake), and restitution (cell-wounding migration) were assessed using
      human colonic HT29 and HCT116 cells. In addition, the effects of recombinant
      24p3/lcn2 on the amount of gastric damage were assessed in rats treated with
      indomethacin (20 mg/kg) and restraint. RESULTS: Marked up-regulation of
      expression of 24p3/lcn2 was seen throughout the gut in response to indomethacin
      or dextran sodium sulfate treatment. Expression was increased particularly in the
      surface epithelial cells and infiltrating inflammatory cells. Proliferation and
      restitution assays in the presence of recombinant wild-type sequence neutrophil
      gelatinase-associated lipocalin, wild-type cys(98)-24p3/lcn2, and mutant ala98
      24p3/lcn2 showed that all 3 peptides caused a 3- to 4-fold increase in
      promigratory activity (P < .01 vs control) but did not influence proliferation.
      The administration of wild-type cys98-, or mutant ala98-24p3/lcn2 (25 and 50
      microg/kg/h, respectively), given via the subcutaneous route, both caused similar
      reductions in the rat gastric damage model (60% reduction at highest dose, P <
      .01 vs control), although oral administration was ineffective. CONCLUSIONS:
      24p3/lcn2 facilitates mucosal regeneration by promoting cell migration.

PMID- 16952551
TI  - Intraepithelial gammadelta+ lymphocytes maintain the integrity of intestinal
      epithelial tight junctions in response to infection.
AB  - BACKGROUND & AIMS: Intestinal epithelial integrity and permeability is dependent
      on intercellular tight junction (TJ) complexes. How TJ integrity is regulated
      remains unclear, although phosphorylation and dephosphorylation of the integral
      membrane protein occludin is an important determinant of TJ formation and
      epithelial permeability. We have investigated the role intestinal intraepithelial
      lymphocytes (iIELs) play in regulating epithelial permeability in response to
      infection. METHODS: Recombinant strains of Toxoplasma gondii were used to assess
      intestinal epithelial barrier function and TJ integrity in mice with intact or
      depleted populations of iIELs. Alterations in epithelial permeability were
      correlated with TJ structure and the state of phosphorylation of occludin. iIEL
      in vivo reconstitution experiments were used to identify the iIELs required to
      maintain epithelial permeability and TJ integrity. RESULTS: In the absence of
      gammadelta+ iIELs, intestinal epithelial barrier function and the ability to
      restrict epithelial transmigration of Toxoplasma and the unrelated intracellular
      bacterial pathogen Salmonella typhimurium was severely compromised. Leaky
      epithelium in gammadelta+ iIEL-deficient mice was associated with the absence of
      phosphorylation of serine residues of occludin and lack of claudin 3 and zona
      occludens-1 proteins in TJ complexes. These deficiencies were attributable to the
      absence of a single subset of gammadelta T-cell receptor (TCR-Vgamma7+) iIELs
      that, after reconstituting gammadelta iIEL-deficient mice, restored epithelial
      barrier function and TJ complexes, resulting in increased resistance to
      infection. CONCLUSIONS: These findings identify a novel role for gammadelta+
      iIELs in maintaining TJ integrity and epithelial barrier function that have
      implications for understanding the pathogenesis of intestinal inflammatory
      diseases associated with disruption of TJ complexes.

PMID- 16952552
TI  - A transient, EMT-linked loss of basement membranes indicates metastasis and poor
      survival in colorectal cancer.
AB  - BACKGROUND & AIMS: Loss of the basement membrane (BM) is considered an important
      step toward tumor malignancy. However, the BM is still expressed in most typical
      colorectal adenocarcinomas; nevertheless, these tumors can invade and develop
      metastases. The aim of this study was to investigate the role, mechanisms, and
      clinical relevance of BM turnover in malignant colorectal cancer (CRC)
      progression. METHODS: Expression of BM components and their transcriptional
      regulation and clinical relevance were investigated in human CRCs and cell lines.
      RESULTS: Our data show new aspects in BM turnover in CRCs with impact on
      malignant tumor progression: (1) The BM is still expressed in the main tumor mass
      of most colorectal adenocarcinomas, but selectively lost at invasive regions of
      the tumor in many cases. (2) Selective loss of the BM at the invasive front has
      high clinical and tumor biologic relevance for distant metastasis and survival.
      (3) The BM is reexpressed in metastases, indicating that its loss is transient
      and regulated by environmental factors. (4) This transient loss is not only due
      to proteolytic breakdown but to a down-regulated synthesis and linked to an
      epithelial-mesenchymal transition (EMT) in tumor cells, and, thereby, zinc-finger
      enhancer protein 1 (ZEB1) is the crucial transcriptional repressor of BM
      components in CRCs. CONCLUSIONS: A transient BM loss at the invasive front is
      correlated with increased distant metastasis and poor patient survival,
      indicating its tumor biologic relevance and usefulness as a prognostic marker.
      Targeting ZEB1 might be a promising therapeutic option to prevent metastasis.

PMID- 16952553
TI  - Recruitment of ataxia-telangiectasia mutated to the p21(waf1) promoter by ZBP-89
      plays a role in mucosal protection.
AB  - BACKGROUND & AIMS: Histone deacetylase inhibitors (HDACi) induce growth arrest,
      apoptosis, and differentiation, particularly in colon cancer cells where they are
      potential chemopreventive agents. HDACi induction of the cyclin-dependent kinase
      inhibitor p21(waf1) has been shown to require ataxia-telangiectasia mutated
      (ATM). Nevertheless, how ATM participates in p21(waf1) gene expression has not
      been defined. METHODS: In vivo protein complexes forming in response to butyrate
      were studied using co-immunoprecipitation and mass spectroscopy. DNA elements in
      the p21(waf1) promoter were analyzed in vivo by chromatin immunoprecipitation and
      in vitro DNA affinity precipitation assays. The expression of p21(waf1) was
      analyzed by immunoblots and reporter assays. RESULTS: Reduction of ZBP-89 or ATM
      with small interfering RNAs blocked HDACi-induced p21(waf1) expression. Chromatin
      immunoprecipitation and DNA affinity precipitation assays showed that both ZBP-89
      and ATM are recruited to the GC-rich DNA elements of the p21(waf1) promoter with
      HDACi treatment. Co-immunoprecipitation revealed that ATM associates with ZBP-89
      in an HDACi-dependent manner. Serial deletions revealed that ATM interacts with
      both the N-terminal and DNA binding domains of ZBP-89. Moreover, we found that
      immunodepletion of ZBP-89 prevented recruitment of ATM to the p21(waf1) promoter
      in vitro. Silencing of ZBP-89 expression blocked HDACi-induced phosphorylation of
      ATM(Ser1981) and p53(Ser15). ATM(Ser1981) phosphorylation in the colons of mutant
      mice expressing an N-terminally truncated form of ZBP-89 was not observed after
      ingestion of dextran sodium sulfate and correlated with exacerbation of the
      mucosal injury. CONCLUSIONS: ZBP-89 interacts with ATM in a butyrate-dependent
      manner and is essential for colonic homeostasis in the setting of acute mucosal
      injury.

PMID- 16952554
TI  - Effect of adiponectin on murine colitis induced by dextran sulfate sodium.
AB  - BACKGROUND & AIMS: Adiponectin, an adipose tissue-derived hormone, exhibits anti
      inflammatory properties and has various biological functions, such as increasing
      insulin sensitivity, reducing hypertension, and suppressing atherosclerosis,
      liver fibrosis, and tumor growth. The aim of the present study was to determine
      the effect of adiponectin on intestinal inflammation. METHODS: We investigated
      the effect of adiponectin on dextran sulfate sodium (DSS)-induced colitis by
      using adiponectin-knockout (APN-KO) mice and an adenovirus-mediated adiponectin
      expression system. We also examined the contribution of adiponectin deficiency to
      trinitrobenzene sulfonic acid (TNBS)-induced colitis. In vitro, we examined the
      effect of adiponectin on intestinal epithelial cells. RESULTS: After
      administration of 0.5% DSS for 15 days, APN-KO mice developed much more severe
      colitis compared with wild-type mice. The messenger RNA expression levels of
      chemokines were significantly higher in the colonic tissues of DSS-treated APN-KO
      mice compared with wild-type mice, accompanied by increased cellular
      infiltration, including macrophages. Adenovirus-mediated supplementation of
      adiponectin significantly attenuated the severity of colitis, but there were no
      differences in the severity of TNBS-induced colitis between the 2 groups.
      Adiponectin receptors were expressed in intestinal epithelial cells, and
      adiponectin inhibited lipopolysaccharide-induced interleukin-8 production in
      intestinal epithelial cells. CONCLUSIONS: Adiponectin is protective against DSS
      induced murine colitis, probably due to the inhibition of chemokine production in
      intestinal epithelial cells and the following inflammatory responses, including
      infiltration of macrophages and release of proinflammatory cytokines.

PMID- 16952555
TI  - Cox-2 is regulated by Toll-like receptor-4 (TLR4) signaling: Role in
      proliferation and apoptosis in the intestine.
AB  - BACKGROUND & AIMS: We recently showed that mice deficient in Toll-like receptor 4
      (TLR4) or its adapter molecule MyD88 have increased signs of colitis compared
      with wild-type (WT) mice after dextran sodium sulfate (DSS)-induced injury. We
      wished to test the hypothesis that cyclooxygenase 2 (Cox-2)-derived prostaglandin
      E2 (PGE2) is important in TLR4-related mucosal repair. METHODS: Cox-2 expression
      was analyzed by real-time polymerase chain reaction, immunohistochemistry,
      Western blotting, and luciferase reporter constructs. Small interfering RNA was
      used to inhibit expression of MyD88. TLR4-/- or WT mice were given 2.5% DSS for 7
      days. Proliferation and apoptosis were assessed using bromodeoxyuridine staining
      and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick
      end labeling assays, respectively. PGE2 was given orally to DSS-treated mice.
      RESULTS: Intestinal epithelial cell lines up-regulated Cox-2 expression in a TLR4
      and MyD88-dependent fashion. Lipopolysaccharide-mediated stimulation of PGE2
      production was blocked by a selective Cox-2 inhibitor or small interfering RNA
      against MyD88. After DSS injury, Cox-2 expression increased only in WT mice. TLR4
      /- mice have significantly reduced proliferation and increased apoptosis after
      DSS injury compared with WT mice. PGE2 supplementation of TLR4-/- mice resulted
      in improvement in clinical signs of colitis and restoration of proliferation and
      apoptosis to WT values. The mechanism for improved epithelial repair may be
      through PGE2-dependent activation of the epidermal growth factor receptor.
      CONCLUSIONS: We describe an important link between TLR4 signaling and Cox-2
      expression in the gut. TLR4 and MyD88 signaling are required for optimal
      proliferation and protection against apoptosis in the injured intestine. Although
      TLR4 signaling is beneficial in the short term, chronic signaling through TLR4
      may lower the threshold for colitis-associated cancer.

PMID- 16952556
TI  - Radixin is required to maintain apical canalicular membrane structure and
      function in rat hepatocytes.
AB  - BACKGROUND & AIMS: Ezrin-radixin-moesin proteins are cross-linkers between the
      plasma membrane and actin filaments. Radixin, the dominant ezrin-radixin-moesin
      protein in hepatocytes, has been reported to selectively tether multidrug
      resistance-associated protein 2 to the apical canalicular membrane. However, it
      remains to be determined if this is its primary function. METHODS: An adenovirus
      mediated short interfering RNA (siRNA) was used to down-regulate radixin
      expression in collagen sandwich-cultured rat hepatocytes and morphologic and
      functional changes were characterized quantitatively. RESULTS: In control
      cultures, an extensive bile canalicular network developed with properly localized
      apical and basolateral transporters that provided for functional excretion of
      fluorescent cholephiles into the bile canalicular lumina. siRNA-induced
      suppression of radixin was associated with a marked reduction in the canalicular
      membrane structure as observed by differential interference contrast microscopy
      and F-actin staining, in contrast to control cells exposed to adenovirus encoding
      scrambled siRNA. Indirect immunofluorescence showed that apical transporters
      (multidrug-resistance-associated protein 2, bile salt export pump, and multidrug
      resistance protein 1) dissociated from their normal location at the apical
      membrane and were found largely associated with Rab11-containing endosomes.
      Localization of the basolateral membrane transporter, organic anion transporting
      polypeptide 2 (Oatp2), was not affected. Consistent with this dislocation of
      apical transporters, the biliary excretion of glutathione-methylfluorescein and
      cholylglycylamido-fluorescein was decreased significantly in the radixin
      deficient cells, but not in the control siRNA cells. CONCLUSIONS: Radixin is
      essential for maintaining the polarized targeting and/or retaining of canalicular
      membrane transporters and is a critical determinant of the overall structure and
      function of the apical membrane of hepatocytes.

PMID- 16952557
TI  - Pancreas recovery following cerulein-induced pancreatitis is impaired in
      plasminogen-deficient mice.
AB  - BACKGROUND & AIMS: The plasminogen (plg) system participates in tissue repair in
      several organs, but its role in pancreas repair remains poorly characterized. To
      understand better the role of plg in pancreas recovery following injury, we
      examined the course of cerulein-induced pancreatitis in plg-deficient and 
      sufficient mice. METHODS: Pancreatitis was induced by cerulein administration (50
      microg/kg, 7 intraperitoneal injections). Mice were killed either at the acute
      phase (7 hours after the first cerulein injection) or during recovery (at 2, 4,
      and 7 days). In pancreatic sections, we examined pancreatic morphology, trypsin
      activation, inflammatory cell infiltration, acinar cell death, cell
      proliferation, extracellular matrix deposition, activation of stellate cells
      (PSCs), and components of the plg and metalloproteinase systems. RESULTS: In plg
      sufficient mice, pancreatic plg levels and plasmin activity increased during the
      acute phase and remained elevated during recovery. Pancreatitis resolved in plg
      sufficient mice within 7 days. Pancreas recovery involved reorganization of the
      parenchyma structure, removal of necrotic debris, cell proliferation, transient
      activation of PSCs, and moderate deposition of extracellular matrix proteins.
      Acute pancreatitis (7 hours) was indistinguishable between plg-deficient and 
      sufficient mice. In contrast, pancreas recovery was impaired in plg-deficient
      mice. Plg deficiency led to disorganized parenchyma, extensive acinar cell loss,
      poor removal of necrotic debris, reduced cell proliferation, and fibrosis.
      Fibrosis was characterized by deposition of collagens and fibronectin, persistent
      activation of PSCs, and up-regulation of pancreatic transforming growth factor
      beta1. CONCLUSIONS: Plg/plasmin deficiency leads to features similar to those
      found in chronic pancreatitis such as parenchymal atrophy and fibrosis.

PMID- 16952558
TI  - Endogenous opioids inhibit early-stage pancreatic pain in a mouse model of
      pancreatic cancer.
AB  - BACKGROUND & AIMS: The endogenous opioid system is involved in modulating the
      experience of pain, the response to stress, and the action of analgesic
      therapies. Recent human imaging studies have shown a significant tonic modulation
      of visceral pain, raising the question of whether endogenous opioids tonically
      modulate the pain of visceral cancer. METHODS: Transgenic mice expressing the
      first 127 amino acids of simian virus 40 large T antigen, under the control of
      the rat elastase-1 promoter, that spontaneously develop pancreatic cancer were
      used to investigate the role of endogenous opioids in the modulation of
      pancreatic cancer pain. Visceral pain behaviors were assessed as degree of
      hunching and vocalization. RESULTS: Although mice with late-stage pancreatic
      cancer displayed spontaneous, morphine-reversible, visceral pain-related
      behaviors such as hunching and vocalization, these behaviors were absent in mice
      with early-stage pancreatic cancer. After systemic administration of the central
      nervous system (CNS)-penetrant opioid receptor antagonists naloxone or
      naltrexone, mice with early-stage pancreatic cancer displayed significant
      visceral pain-related behaviors, whereas systemic administration of the CNS
      nonpenetrant opioid antagonist naloxone-methiodide did not induce an increase in
      visceral pain behaviors. CONCLUSIONS: Our findings suggest that a CNS opioid
      dependent mechanism tonically modulates early and late-stage pancreatic cancer
      pain. Understanding the mechanisms that mask this pain in early stage disease and
      drive this pain in late-stage disease may allow improved diagnosis, treatment,
      and care of patients with pancreatic cancer.

PMID- 16952560
TI  - Successful pregnancy in a Crigler-Najjar type I patient treated by phototherapy
      and semimonthly albumin infusions.

PMID- 16952559
TI  - Cholangiocyte cilia detect changes in luminal fluid flow and transmit them into
      intracellular Ca2+ and cAMP signaling.
AB  - BACKGROUND & AIMS: Cholangiocytes have primary cilia extending from the apical
      plasma membrane into the ductal lumen. While the physiologic significance of
      cholangiocyte cilia is unknown, studies in renal epithelia suggest that primary
      cilia possess sensory functions. Here, we tested the hypothesis that
      cholangiocyte cilia are sensory organelles that detect and transmit luminal bile
      flow stimuli into intracellular Ca2+ ([Ca2+]i) and adenosine 3',5'-cyclic
      monophosphate (cAMP) signaling. METHODS: Scanning electron microscopy,
      transmission electron microscopy, and immunofluorescent confocal microscopy of
      rat isolated intrahepatic bile duct units (IBDUs) were used to detect and
      characterize cholangiocyte cilia. The fluid flow-induced changes in Ca2+ and cAMP
      levels in cholangiocytes of microperfused IBDUs were detected by epifluorescence
      microscopy and a fluorescence assay, respectively. RESULTS: In microperfused
      IBDUs, luminal fluid flow induced an increase in [Ca2+]i and caused suppression
      of the forskolin-stimulated cAMP increase. The fluid flow-induced changes in
      [Ca2+]i and cAMP levels were significantly reduced or abolished when cilia were
      removed by chloral hydrate or when ciliary-associated proteins polycystin-1 (a
      mechanoreceptor), polycystin-2 (a Ca2+ channel), and the Ca2+-inhibitable
      adenylyl cyclase isoform 6 were individually down-regulated by small interfering
      RNAs. CONCLUSIONS: Cholangiocyte cilia are sensory organelles containing
      polycystin-1, polycystin-2, and adenylyl cyclase isoform 6 through which luminal
      fluid flow affects both [Ca2+]i and cAMP signaling in the cell. The data suggest
      a new model for regulation of ductal bile secretion involving cholangiocyte
      cilia.

PMID- 16952562
TI  - Nonalcoholic fatty liver disease: Cytokine-adipokine interplay and regulation of
      insulin resistance.

PMID- 16952561
TI  - Gene expression profiling reveals stromal genes expressed in common between
      Barrett's esophagus and adenocarcinoma.
AB  - BACKGROUND & AIMS: Barrett's esophagus is a precursor of esophageal
      adenocarcinoma. DNA microarrays that enable a genome-wide assessment of gene
      expression enhance the identification of specific genes as well as gene
      expression patterns that are expressed by Barrett's esophagus and adenocarcinoma
      compared with normal tissues. Barrett's esophagus length has also been identified
      as a risk factor for progression to adenocarcinoma, but whether there are
      intrinsic biological differences between short-segment and long-segment Barrett's
      esophagus can be explored with microarrays. METHODS: Gene expression profiles for
      endoscopically obtained biopsy specimens of Barrett's esophagus or esophageal
      adenocarcinoma and associated normal esophagus and duodenum were identified for
      17 patients using DNA microarrays. Unsupervised and supervised approaches for
      data analysis defined similarities and differences between the tissues as well as
      correlations with clinical phenotypes. RESULTS: Each tissue displays a unique
      expression profile that distinguishes it from others. Barrett's esophagus and
      esophageal adenocarcinoma express a unique set of stromal genes that is distinct
      from normal tissues but similar to other cancers. Adenocarcinoma also showed
      lower and higher expression for many genes compared with Barrett's esophagus. No
      difference in gene expression was found between short-segment and long-segment
      Barrett's esophagus. CONCLUSIONS: The genome-wide assessment provided by current
      DNA microarrays reveals many candidate genes and patterns not previously
      identified. Stromal gene expression in Barrett's esophagus and adenocarcinoma is
      similar, indicating that these changes precede malignant transformation.

PMID- 16952563
TI  - The rise and fall (and rise?) of endoscopic anti-reflux procedures.

PMID- 16952564
TI  - The host or the virus? Impact of genetic factors on the outcome of hepatitis C
      virus infection.

PMID- 16952565
TI  - Immunosuppression, hepatitis B virus variants: Synergistic role in hepatic
      fibrogenesis.

PMID- 16952566
TI  - Epigenetic silencing of genes in human colon cancer.

PMID- 16952567
TI  - Unintentional acetaminophen-induced acute liver failure in the United States:
      Time for action?

PMID- 16952569
TI  - Helicobacter pylori in gastric cancer: Friend or foe?

PMID- 16952568
TI  - C difficile--C'est Difficile?

PMID- 16952570
TI  - Adipose deposition and Barrett's esophagus: Is all fat created equal?

PMID- 16952572
TI  - Double-balloon endoscopy: Extending the arm of the gastroenterologist.

PMID- 16952573
TI  - Neither LKB1 nor AMPK are the direct targets of metformin.

PMID- 16952575
TI  - Comprehensive mucosal visualization at optical colonoscopy: Technique remains the
      key.

PMID- 16952576
TI  - Prognostic value of KIT exon 11 deletions in GISTs.

PMID- 16952578
TI  - DSRS versus TIPS for variceal bleeding: Lessons from late follow-up of 507 DSRS
      patients.

PMID- 16952579
TI  - Pediatric anorectal impalement with bladder rupture: case report and review of
      the literature.
AB  - Rectal impalement involves foreign body trauma to the anus or rectum resulting in
      intra- or extraperitoneal rupture. Evaluation of suspected rectal impalement
      injury involves careful history and physical examination. Ruling out rectal
      perforation in patients with reported impalement is critical even if there is no
      evidence of trauma to the perineum. There are few reports on pediatric impalement
      and only 1 reported case of pediatric rectal impalement with bladder rupture. We
      report a rectal impalement with extraperitoneal bladder injury in a 12-year-old
      boy and review the literature on treatment of these injuries.

PMID- 16952580
TI  - Dorsal mesenteric agenesis without small bowel atresia: a rare cause of midgut
      volvulus in children.
AB  - Agenesis of the dorsal mesentery in association with jejunal atresia is a well
      recognized congenital anomaly. Only few reports exist in the English literature
      of children with agenesis of the dorsal mesentery without small bowel atresia.
      Herein, we report a child with total mesenteric agenesis presenting with midgut
      volvulus owing to internal herniation of the small bowel through a mesenteric
      defect, with normal fixation and rotation of the bowel.

PMID- 16952581
TI  - Clinical characteristics and outcome of Wilms tumors with a favorable histology
      in Japan: a report from the Study Group for Pediatric Solid Malignant Tumors in
      the Kyushu Area, Japan.
AB  - BACKGROUND/PURPOSE: Since 1996, the standard treatment of Wilms tumors in Japan
      has been based on the regimen of the Japanese Wilms Tumor Study. However, in
      Japan, there have been no reports about Wilms tumors that analyzed the clinical
      features and patient outcome in a large series until now. This study aims to
      assess the clinical characteristics of patients with Wilms tumor with a favorable
      histology from a retrospective standpoint in the Kyushu area in Japan and,
      furthermore, to analyze the historical changes of clinical features and outcome
      from the 1980s to the 1990s. METHODS: Between 1982 and 1996, 90 cases of Wilms
      tumors with a favorable histology were registered in the Kyushu area. Regarding
      the clinical feature and outcome, they were divided into 2 groups (group A, 1982
      1989, n = 50; group B, 1990-1996, n = 40). The outcome was analyzed based on the
      5-year overall survival rate. RESULTS: The clinical features (age, sex, initial
      symptom, location, stage) demonstrated no definite differences between group A
      and group B. Regarding the operation, the rate of an initial complete resection
      in the early stages was significantly higher in group B than in group A. All
      stage V cases in group B undewent a bilateral tumor biopsy instead of a radical
      nephrectomy as the initial operation. The 5-year overall survival rate throughout
      the whole period was 87.8%, whereas the rates were 84.0% for group A and 90.0%
      for group B (P = NS), respectively. Of particular note, the outcome of patients
      with stage I and stage V in group B substantially improved in comparison to that
      in group A. However, in advanced cases, no significant improvement in the outcome
      was noted. CONCLUSIONS: This is the first report about the clinical features and
      outcome for Wilms tumors with a favorable histology in Japan from the 1980s to
      the 1990s. The present study suggested that in the early-stage cases, an
      initially complete resection followed by standard postoperative chemotherapy
      substantially improved the outcome of the patients in group B. In the stage V
      cases, the performance of renal salvage surgery may have positively contributed
      to the improvement in the outcome in group B. However, in the advanced stage
      cases, no definite improvement was noted. In the future, an improved efficacy of
      the treatments for Wilms tumors based on the standard protocol established by the
      Japanese Wilms Tumor Study in 1996 is expected in Japan.

PMID- 16952582
TI  - Prognostic significance of biochemical heterogeneity of catecholaminergic clones
      in neuroblastoma.
AB  - BACKGROUND/PURPOSE: Genetic heterogeneity of neuroblastic tumors leads to
      biochemical changes that manifest themselves in different symptoms and clinical
      courses, which may vary from spontaneous regression and remission to progression
      with fatal outcome. METHODS: To test the hypothesis that ratios of dopamine (DA)
      to noradrenaline and of DA to vanillylmandelic acid reflect the composition of
      adrenergic clones and tumor heterogeneity, we determined urinary DA/noradrenaline
      and DA/vanillylmandelic acid ratios that presumably reflect DA-beta-hydroxylase
      (DBH) activity and the prognostic values thereof. RESULTS: Based on catecholamine
      metabolism, 4 model situations were defined: (a) complete block of DBH in all
      cells; (b) block of DBH in some cells; (c) a different enzymatic block; and (d)
      normal DBH activity in the population of tumor-forming cells. Normal DBH activity
      was encountered most frequently in children younger than 2 years and in tumors
      representing favorable prognostic stages (I, II, and IVS). Surviving children
      with stage IV neuroblastoma presented with tumors composed primarily of cells
      without the DBH block. Further stratification of 2 prognostically poor groups
      (stages IV and III + IV) was possible with respect to DBH activity. CONCLUSIONS:
      Differential production of neurotransmitters in a population of tumor cells may
      be explained in terms of tumor heterogeneity.

PMID- 16952583
TI  - Sacrococcygeal teratoma--a 25-year experience in a UK regional center.
AB  - BACKGROUND: Sacrococcygeal teratoma (SCT) is uncommon (1:35,000-1:40,000
      newborns). We report a 25-year single-center experience with a focus on late
      effects. METHODS: Surgical and tumor registries identified patients with SCT
      between 1977 and 2001. Perinatal data, associated anomalies, operative findings,
      histology, and survival were recorded. Continence was assessed clinically.
      Urodynamics and anorectal manometry were performed as indicated. RESULTS: Thirty
      three patients (28 females) were treated for SCT. Before 1988, 2 of 18 were
      diagnosed antenatally compared with 8 of 15 between 1988 and 2001. Ten babies
      were delivered by cesarean birth. Seven children presented after the neonatal
      period. Surgery comprised tumor excision with coccygectomy. Histology was benign
      in 26 (79%), malignant in 6 (18%), and immature in a single patient. Presentation
      beyond the newborn period was associated with malignant disease and poorer
      outcome. Overall survival was 94%. Neuropathic bladder or bowel disturbance was
      identified in 7 of 20 patients on long-term follow-up. CONCLUSIONS: Antenatal
      diagnosis of SCT appears to be increasing. Parental counseling should include the
      continence problems that may follow removal of even benign tumors. Resection by
      surgical oncologists and reconstruction by colorectal specialists may improve
      function. Follow-up by oncologists, surgeons, and urologists remains an important
      part of SCT management.

PMID- 16952584
TI  - Prenatally diagnosed sacrococcygeal teratoma: a prognostic classification.
AB  - PURPOSE: The objective of this study is to describe a prognostic classification
      for prenatally diagnosed sacrococcygeal teratoma (SCT). METHODS: Charts from 44
      fetuses were reviewed. Three groups were defined as follows: group A--tumor
      diameter less than 10 cm, absent or mild vascularity and slow growth; group B-
      diameter 10 cm or greater, pronounced vascularity or high-output cardiac failure
      and fast growth; group C--diameter 10 cm or greater, predominantly cystic lesion
      with absent or mild vascularity and slow growth. RESULTS: Size at diagnosis,
      growth rate, and vascularity were higher in group B. Gestational age at delivery
      was lower in group B. Eleven of 21 died in the perinatal period in group B and
      none in groups A and C. In group C, drainage or shunting of the SCT has been
      performed in 6 of 10 cases. CONCLUSIONS: Group A is associated to good maternal
      and perinatal outcome, as well as group C, although shunting or drainage of the
      SCT could be necessary. Large fast-growing SCT with rich vascularity is
      associated with a higher perinatal mortality and morbidity than smaller lesions
      with mild vascularity.

PMID- 16952585
TI  - The role of laparotomy for intestinal perforation in very low birth weight
      infants.
AB  - BACKGROUND/PURPOSE: The management of intestinal perforation in very low birth
      weight (VLBW) infants (less than 1500 g) is controversial. Current practice
      favors peritoneal drainage (PD) with or without a delayed laparotomy over primary
      laparotomy (PL). We compared the outcomes of PD +/- delayed laparotomy vs PL in
      VLBW infants using the Score for Neonatal Acute Physiology with Perinatal
      Extension (SNAPPE-II) as a validated predictor of mortality. METHODS: A
      retrospective analysis (1998-2003) of VLBW infants with intestinal perforation at
      2 pediatric centers was undertaken. Data retrieval included neonatal demographics
      and parameters for SNAPPE-II calculation. The primary end point was 30-day
      mortality. Other outcome measures included in-hospital mortality, days fasting,
      days to extubation, and length of stay. Statistical analysis was performed with
      either Student's t test or chi2 analysis. Subgroup and multivariate analyses were
      also performed. P values < .05 were considered significant. RESULTS: Fifty-two
      neonates (25 PD, 27 PL) were reviewed. Overall, 10 (19.2%) infants died. Observed
      30-day mortality rates in PD and PL groups were 32% and 7.4% (P = .028),
      respectively. Average SNAPPE-II scores for PD (42.5 +/- 20.8) and PL (25.1 +/-
      14.6) groups yielded predicted mortality rates of 15.7% and 4.9% (P = .001),
      respectively. PD group 30-day mortality far exceeded the rate predicted by the
      SNAPPE-II score. Days fasting (13.7 vs 20.4; P = .0001), days to extubation (26.7
      vs 51.5; P = .014), and length of stay (56.1 vs 83.6; P = .031) all favored the
      PL group despite incorporating SNAPPE-II score as a covariate into the
      multivariate analysis. Of the 25 patients receiving drainage, 9 underwent PD
      alone (SNAPPE-II = 46.6 +/- 27.9), whereas 16 patients underwent delayed
      laparotomy (SNAPPE-II = 37.8 +/- 17.6). The PD-only group had a greatly elevated
      mortality rate (77.8% vs 15.7% predicted), whereas the delayed laparotomy group
      had a reduced mortality rate (6.3% vs 9.3% predicted). CONCLUSION: Our data
      suggest that laparotomy, either alone or after PD, provides an improved outcome
      in VLBW infants with intestinal perforation. PD should be used as a temporizing
      measure until laparotomy can be performed.

PMID- 16952586
TI  - Alpha glutathione S-transferase: a potential marker of ischemia-reperfusion
      injury of the intestine after cardiac surgery?
AB  - BACKGROUND: The aim of the study was to assess the utility of alpha glutathione S
      transferase (alphaGST) as a potential marker of intestinal ischemia-reperfusion
      injury in children after cardiac surgery. METHODS: Twenty-six patients undergoing
      cardiac surgery were enrolled in this longitudinal experimental study. Blood
      samples were drawn for analysis at specified time points during surgery and
      analyzed for alphaGST levels. Clinical indices of splanchnic morbidity were
      assessed up to discharge from hospital. Results were analyzed using Mann-Whitney
      tests and linear mixed effects models. RESULTS: Two groups were identified. Group
      1 (n = 16) showed no intestinal morbidity and group 2 (n = 10) had signs of
      intestinal morbidity. Statistical differences were shown between the 2 groups
      with respect to time with aortic cross-clamp (ACC) in situ, time on cardiac
      bypass, duration of operation, time to enteral feeding and full feeding, time on
      mechanical ventilation, and time in the intensive care unit postoperatively. The
      serum concentration of alphaGST was significantly higher for group 2 and this
      rise was greatest after removal of the ACC. CONCLUSIONS: AlphaGST showed
      significant elevation in patients with prolonged bypass times and ACC times.
      These patients also displayed signs of intestinal morbidity, suggesting that this
      marker may be useful in screening patients at risk for intestinal pathology. This
      rise in alphaGST was associated with a prolonged ischemia time, and was greatest
      after the cross-clamp was released, suggesting that it is a postischemic
      reperfusion phenomenon leading to its elevation. A low alphaGST level appears to
      exclude significant intestinal ischemia.

PMID- 16952587
TI  - Myocardium expression of connexin 43, SERCA2a, and myosin heavy chain isoforms
      are preserved in nitrofen-induced congenital diaphragmatic hernia rat model.
AB  - BACKGROUND: Previous morphological studies had produced controversial results
      with regard to heart development in congenital diaphragmatic hernia (CDH),
      whereas a few publications investigated cardiac function and myocardial
      maturation. Myocardium maturation is associated with age-dependent increasing of
      gene expression of gap junction protein connexin 43 (Cx43), adenosine
      triphosphatase of the sarcoplasmic reticulum (SERCA2a), as well as switching of
      myosin heavy chains (MHCs) from beta to alpha isoforms. Our aim was to evaluate
      myocardium maturity in nitrofen-induced CDH rat model. METHODS: Fetuses from
      dated pregnant Sprague-Dawley rats were assigned to 3 experimental groups:
      control, nitrofen (exposed to nitrofen, without CDH), and CDH (exposed to
      nitrofen, with CDH). Myocardial samples collected from left ventricle free wall
      were processed to (i) quantification of messenger RNA (mRNA) of Cx43, SERCA2a,
      alpha and beta MHC isoforms, as well as beta-actin (housekeeping gene); and (ii)
      separation of MHC isoforms (alpha and beta isoforms) by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis silver stained. RESULTS: We demonstrated that
      there is no difference in myocardial gene expression of Cx43 (control, 1.0 +/-
      0.1; nitrofen, 1.1 +/- 0.2; CDH, 1.3 +/- 0.2) and SERCA2a (control, 1.0 +/- 0.1;
      nitrofen, 0.9 +/- 0.1; CDH, 1.0 +/- 0.2). Myocardial gene expressions of alpha
      and beta mRNA of MHC isoforms were slightly decreased both in nitrofen and CDH
      fetuses when compared with control fetuses, but evaluation of the alpha-to-beta
      ratios of MHC isoforms at protein level revealed no significant differences
      between CDH and control (control, 16.9 +/- 2.5; CDH, 17.0 +/- 2.0). CONCLUSIONS:
      Myocardial quantification of Cx43 and SERCA2a mRNA, as well as the expression
      pattern of MHC isoforms at protein levels, was similar in all studied groups. We
      predict, therefore, that acute heart failure commonly observed in CDH infants
      might be attributed predominantly to cardiac overload secondary to severe
      pulmonary hypertension rather than to myocardial immaturity.

PMID- 16952588
TI  - Minimally invasive management of bile leaks after blunt liver trauma in children.
AB  - BACKGROUND: Management of bile leaks after blunt abdominal trauma remains
      controversial. Conventionally, open surgery has been considered necessary, but
      new modalities of treatment, including endoscopic biliary stenting and
      laparoscopy, offer a minimally invasive alternative. MATERIALS AND METHODS: A
      retrospective review of all cases of blunt liver trauma in children treated at
      our institution between May 2002 and October 2004 was performed looking for
      possible biliary injury. RESULTS: Five children (3 boys), median age 13 years
      (range, 10-15 years), were referred to our institution at a median time of 4 days
      (1-15 days) after the initial trauma. Mechanism of injury was motor vehicle
      accident (n = 3), fall from a motorbike/Quad bike (n = 2), and a scooter
      handlebar injury (n = 1). Two, who were hemodynamically unstable, required
      laparotomy within 24 hours, although their subsequent management was minimally
      invasive. Endoscopic retrograde cholangiopancreatography, performed at a median
      time of 15 days (2-28 days), demonstrated an intrahepatic biliary leak in all 5
      patients. Biliary stenting was performed in each case, with 2 also having a
      sphincterotomy. One subsequently developed a bile duct stricture that was managed
      by endoscopic dilatation. Four required additional percutaneous external drainage
      of intraabdominal collections. Two underwent laparoscopy to facilitate peritoneal
      lavage and rule out bowel injuries. No child required open surgery to treat the
      bile leak. Median hospital stay was 43 days (range, 15-58 days). CONCLUSIONS: A
      minimally invasive, multidisciplinary approach to traumatic bile leaks, as an
      alternative to open surgery, is practical and safe. It requires flexibility,
      particularly if the diagnosis has been delayed, and may still involve a prolonged
      hospital stay.

PMID- 16952589
TI  - Gallbladder wall inflammatory cells in pediatric patients with biliary dyskinesia
      and cholelithiasis: a pilot study.
AB  - BACKGROUND/PURPOSE: Inflammation has been implicated in functional
      gastrointestinal disorders, including functional dyspepsia and irritable bowel
      syndrome. This study was undertaken to evaluate gallbladder wall inflammatory
      cells in children with abdominal pain related to gallstones and biliary
      dyskinesia to determine the candidate cell types that may be contributing to the
      pathophysiology of these entities. METHODS: Gallbladder specimens from 20
      patients with cholelithiasis, 20 biliary patients with dyskinesia, and 12 autopsy
      controls were evaluated in a blinded fashion. Eosinophil, tryptase-positive, and
      CD3+ cell densities were determined for the lamina propria and muscularis mucosa
      layers and compared between groups. RESULTS: Patients with biliary dyskinesia and
      cholelithiasis had a 9- to 12-fold increase in mean and peak mast cell densities,
      respectively, in both layers as compared with controls. Peak (13.7 vs 8.4) and
      mean (9.2 vs 5.2) CD3+ cell densities were increased in the muscularis mucosae of
      cholelithiasis specimens as compared with biliary dyskinesia specimens.
      CONCLUSION: Gallbladder wall inflammatory cell densities, particularly mast
      cells, differ between children with cholelithiasis, children with biliary
      dyskinesia, and controls. Future studies are warranted to define the roles for
      specific inflammatory cell types.

PMID- 16952590
TI  - Magnetic resonance imaging measurement of the anorectal striated muscle complex
      in normal children.
AB  - PURPOSE: The aim of the study was to describe and establish a normal measurement
      of the striated muscle complex (SMC) in healthy children using body phased-array
      or head coil magnetic resonance imaging. METHODS: Imaging was performed in 20
      boys and 20 girls (age range, from 3 months to 14 years; average age, 3.2 years)
      without anorectal disorders. The dimensions of the puborectalis muscle (PR) and
      external anal sphincter (EAS) were measured in different planes. RESULTS: There
      was a close positive correlation between absolute width and length of SMC and age
      (P < .05), whereas there was no correlation between the relative width and length
      of SMC and age (P > .05). Normal relative length of the PR and EAS were measured
      as 0.47 +/- 0.04 and 0.41 +/- 0.04, respectively, and the normal relative width
      of PR and posterior EAS were 0.50 +/- 0.04 and 0.44 +/- 0.04 in children younger
      than 14 years. CONCLUSIONS: The width and length of PR and EAS increase
      progressively with age. The relative width and length of PR and EAS were not
      variable with age. A relative width and length of PR and EAS were chosen as
      objective criteria for normal SMC in children younger than 14 years.

PMID- 16952591
TI  - Clinical outcome of cystic fibrosis presenting with or without meconium ileus: a
      matched cohort study.
AB  - OBJECTIVE: This matched case-control study compared the nutritional and the
      pulmonary long-term outcomes of cystic fibrosis (CF) patients presenting a
      history of meconium ileus (MI) with early-diagnosed symptomatic CF without MI
      (non-MI). MATERIAL AND METHOD: Twenty-six patients with CF treated for MI between
      1980 and 1997 have been matched for sex, birth date, and earliest CF symptomatic
      diagnosis for the children with non-MI CF. Clinical characteristics, genotype and
      complications were evaluated as well as the progression of the CF disease from
      infancy to 15 years old by nutritional status (z score weight, z score height),
      pulmonary function tests (PFTs) (FVC and FEV1), and Pseudomonas aeruginosa
      acquisition. RESULTS: Median duration of the follow-up was 12.5 years (range, 10
      17 years). Genotype identification showed no significant difference. Further on,
      the rate of complications and the occurrence of chronic P. aeruginosa
      colonization did not differ. At age of 15 years (n = 13), nutritional status and
      PFTs did not demonstrate any significant difference. CONCLUSION: These results
      suggest that adequate initial nutritional and medical management of MI allows
      further similar nutritional status and PFTs compared with other early-diagnosed
      symptomatic CF patients. In this study, MI did not represent an additional risk
      factor for the patient's life.

PMID- 16952592
TI  - Outcome of total splenectomy with portosystemic shunt for massive splenomegaly
      and variceal bleeding in cystic fibrosis.
AB  - Multilobular biliary cirrhosis and portal hypertension are frequent complications
      of cystic fibrosis liver disease, leading to esophageal varices and splenomegaly.
      Therapy is focused on variceal bleeding control; however, reduction of spleen
      volume is also important to restore gastric volume and resolve invalidating
      abdominal discomfort. We report long-term follow up (median duration, 5.5 years;
      range, 14 months-21.5 years) of 6 patients with cystic fibrosis (4 men, 2 women;
      median age, 14 years; range, 8-18 years) who underwent splenectomy with a
      splenorenal shunt operation. Three patients received elective surgery for massive
      splenomegaly with important abdominal discomfort, recurrent variceal bleeding,
      and hypersplenism. Three were urgently treated to control variceal bleeding after
      several sessions of sclerotherapy. All but 2 received antipneumococcal
      vaccination before surgery. Four patients had a weight gain of 10% within 3
      months of surgery, and 3 developed spontaneous puberty. Lung function remained
      stable, and there was an overall reduction of respiratory tract infections. The
      youngest patient, however, died of overwhelming septicemia during treatment with
      steroids. Although total splenectomy has important risks, in well-selected cases,
      it can have benefits. Immuno- and chemoprophylaxis, combined with patient
      awareness of supplementary risk of infections is indispensable to minimize septic
      complications.

PMID- 16952593
TI  - Effects of glutamic acid and taurine on total parenteral nutrition.
AB  - BACKGROUND: The objective of the present study was to ascertain whether
      simultaneous administration of glutamic acid (Glu) and taurine (Tau) to patients
      on total parenteral nutrition (TPN) could improve intestinal mucosal atrophy and
      suppress bacterial translocation. METHODS: A 5-day TPN study was conducted in 5
      week-old Sprague-Dawley rats. Commercially available Glu was used for TPN in
      group G and was enhanced with Tau (500 mg kg(-1) day(-1)) in group GT. Oral
      nutrition was provided in group C controls. At 5 days, amino acid and cytokine
      levels in plasma and endotoxin levels in portal blood were measured. The
      histology of the small intestine, liver, and lung were analyzed. RESULTS: Mucosal
      thickness and villus height in the small intestine were lower for group G than
      for groups C and GT. Taurine level in group GT was higher than in group G.
      Arginine and citrulline levels in groups G and GT were lower than in group C.
      Taurine level in the small intestine was greater in group GT than in group G.
      Citrulline concentration was lower in group G than in groups GT and C. Endotoxin
      level in portal blood and cytokine (tumor necrosis factor alpha, interleukin
      1beta, and interleukin-6) levels in blood tended to be lower for group GT than
      for group G, but no significant differences were noted. Immunostaining showed
      strong positive reactions to vascular cell adhesion molecule-1 in the liver and
      lung for group G, and milder reactions for group GT. CONCLUSIONS: Simultaneous
      administration of Glu and Tau improved small intestinal mucosal thickness and
      villus height during TPN. Levels of Tau in the small intestine and plasma
      increased, and the level of citrulline in the small intestine improved. Decreased
      expression of adhesion molecules in the liver and lung and improved
      microcirculation in the liver were also confirmed.

PMID- 16952594
TI  - Classification of the dysmorphology of pectus excavatum.
AB  - BACKGROUND/PURPOSE: To describe the dysmorphology of pectus excavatum, the most
      common congenital chest wall anomaly. METHODS: A stratified sample of 64
      patients, representative of a patient population with pectus excavatum of the
      Children's Hospital of King's Daughters in Norfolk, VA, was described and
      classified. The sample was stratified by sex to represent a 4:1 male-to-female
      ratio. The sample was further stratified to represent categories of age (3-10, 11
      16, and 17 years and older). Preoperative photos and baseline chest computed
      tomography scans were examined and categorized according to the chief criteria,
      including asymmetry/symmetry of the depression, localized vs diffuse morphology,
      sternal torsion, cause of asymmetric appearance, and the length of the
      depression. RESULTS: Useful morphologic distinctions in pectus excavatum are
      localized depressions vs diffuse depressions, short and long length, symmetry,
      sternal torsion, slope/position of absolute depth, and unique patterns such as
      the horns of steer depression. CONCLUSIONS: These classifications simplify the
      diagnosis of pectus excavatum, aid in corrective surgery, and should improve
      correlation of phenotype and genotype in future genetic analysis.

PMID- 16952595
TI  - Complications associated with an implantable vascular access device.
AB  - PURPOSE: Implantable vascular access devices (ports) are well accepted in the
      management of many pediatric conditions. Modifications have improved port
      function, patient satisfaction, and enhanced compatibility with imaging studies.
      We reviewed our experience with a port system and identified unique mechanical
      complications. METHODS: From 1998 to the present, 301 patients underwent 296 port
      insertions and 175 port removals. We assessed medical records, radiographs, and
      operative findings. The 6.6F MRI Low-Profile Implanted Port (Bard Access Systems,
      Salt Lake City, Utah) was used almost exclusively and was assembled by the
      operating surgeon. Outcome measures included port reservoir leakage, catheter
      dislodgment, and number of device days until complication. Ports were implanted
      for multiple medical problems including 74.2% in hematology/oncology patients.
      RESULTS: For 296 port insertions, 15 complications (5.1%) were identified in 13
      patients (mean age, 8.4 years). Eleven leaks (3.7%) in 9 patients were found,
      with 9 leaks resulting from needle perforation of the port base and 2 leaks seen
      at the catheter connection site. Average port duration was 425 days (range, 12
      1266 days) before leakage. Four patients had catheter dislodgment (1.4%), with 3
      of 4 catheters embolizing to the heart or pulmonary artery. Patients were
      asymptomatic, and catheters were retrieved by interventional radiology.
      Dislodgment at the catheter-port connection site was seen in 3 of 4 cases, and
      average port duration was 1075 days (range, 269-2657 days) until catheter
      separation. Twelve of 13 patients had successful implantation of a new port
      system. CONCLUSIONS: This study identifies that (1) mechanical port complications
      (5.1%) are not rare for this device; (2) regardless of port age, the thin plastic
      base may result in a risk of perforation not seen in other devices; (3) the
      extended period before embolization likely indicates device wear rather than
      faulty assembly; and (4) complications could be successfully managed including
      retrieval of embolized catheters.

PMID- 16952596
TI  - Primary paraesophageal hernia in children.
AB  - BACKGROUND: Paraesophageal hernias are uncommon in children and are distinctively
      different from the more common sliding hiatus hernias and those occurring after
      antireflux surgery in anatomy, pathology, symptoms, complications, and
      management. We reviewed a single institution's experience with the pathology of
      paraesophageal hernias. METHODS: We conducted a retrospective analysis of patient
      records. RESULTS: Fifty-nine children with paraesophageal hernias were treated
      during a 42-year period. Their mean age at presentation was 23.4 months (range, 1
      day to 11 years). Presenting complaints were recurrent chest infections (n = 32),
      vomiting (n = 24), symptomatic anemia (n = 20), failure to thrive (n = 18), and
      dysphagia (n = 6). Five children were asymptomatic, and their diagnosis was
      established when they were investigated for incidentally noted asymptomatic
      anemia (n = 3), scoliosis (n = 2), and mumps (n = 1). Radiology typically showed
      cystic masses in the posterior mediastinum in the right lower chest and
      occasionally had an air-fluid level in the cystic mass or a dilated esophagus.
      None presented with strangulation or hematemesis. All patients were operated on.
      Surgical findings included a peritoneal lined sac and herniation through a
      widened diaphragmatic hiatus, containing the stomach and at times the transverse
      colon, spleen, and small bowel. The hernial sac usually occurred on the right.
      Principles of surgery included reduction of the contents, partial excision of the
      sac, crural approximation, and a fundoplication in 39 patients. No fundoplication
      was done in the earlier years in 20 patients, of whom 12 had recurrent reflux
      symptoms. Postoperative complications were bowel obstruction (n = 6),
      intussusception (n = 3), dysphagia (n = 3), breakdown of the repair (n = 3), and
      pneumothorax (n = 1). There was one mortality caused by preoperative aspiration.
      CONCLUSION: Paraesophageal hernias in children are uncommon and most likely
      caused by a congenital defect. They are associated with considerable morbidity.
      Strangulation is not a feature. Principles of repair are well established and
      should include an antireflux procedure.

PMID- 16952597
TI  - Defective in vitro contractility of ureteropelvic junction in children with
      functional and obstructive urine flow impairment.
AB  - BACKGROUND/PURPOSE: Studies of children with urinary flow impairment (UFI) at the
      ureteropelvic junction (UPJ) have revealed prestenotic, stenotic, and
      poststenotic histologic changes. Muscle function, however, has not been
      investigated. We therefore evaluated in vitro UPJ contractility by tensiometry in
      children with UFI. METHODS: Freshly excised UPJs from 11 children with UFI (6
      functional, 5 obstructive) were each divided into 3 parallel, prestenotic,
      stenotic, and poststenotic rings, and those from 7 children with Wilms' tumor
      were divided into proximal, medial, and distal segments. Each ring was studied in
      vitro by tensiometry in the basal state and after stimulation with 25 and 60
      mmol/L KCl. RESULTS: The stenotic rings from the UFI subjects displayed a
      significantly lower basal contractility than the other 2 rings, and their 25 and
      60 mmol/L KCl-induced contractility was absent or severely reduced, whereas the
      values of these parameters were similar to that observed in controls in the other
      2 rings of patients with either functional or obstructive UFI. CONCLUSIONS: Basal
      and KCl-induced contractility of the stenotic segment is severely impaired in
      children and infants with either functional or obstructive UFI, whereas the
      contractility of their pre- and poststenotic UPJ segments is similar to that
      recorded in controls.

PMID- 16952598
TI  - Immediate nipple pain relief after frenotomy in breast-fed infants with
      ankyloglossia: a randomized, prospective study.
AB  - PURPOSE: Ankyloglossia ("tongue-tie") occurs in nearly 5% of neonates, but its
      clinical significance relating to breast-feeding difficulties is controversial.
      We tested the hypothesis that in infants with ankyloglossia referred because of
      breast-feeding difficulties, frenotomy alleviates the symptoms. METHODS: Twenty
      five mothers of healthy infants with ankyloglossia were recruited because of sore
      nipples. Infants were randomized to either of 2 sequences: (1) frenotomy, breast
      feeding, sham, breast-feeding (n = 14) or (2) sham, breast-feeding, frenotomy,
      breast-feeding (n = 11). The mothers as well as all personnel taking care of the
      child after each sham or frenotomy procedure were masked as to the study
      sequence. In every sequence, and after each sham or frenotomy procedure, a
      standardized latch score and pain score were obtained from the mother. RESULTS:
      There was a significant decrease in pain score after frenotomy than after sham (P
      = .001). There was also a nearly significant improvement in latch after the
      frenotomy in these mothers (P = .06). CONCLUSION: Frenotomy appears to alleviate
      nipple pain immediately after frenotomy. We speculate that ankyloglossia plays a
      significant role in early breast-feeding difficulties, and that frenotomy is an
      effective therapy for these difficulties.

PMID- 16952599
TI  - Cutaneous lipoma in children: 5 cases with Bannayan-Riley-Ruvalcaba syndrome.
AB  - Cutaneous lipoma is rare in children, but it can be part of a syndrome such as
      the Bannayan-Riley-Ruvalcaba syndrome (BRRS). The BRRS is a dominant autosomal
      disorder characterized by cutaneous lipomas, macrocephaly, intestinal polyps, and
      developmental delay associated with PTEN gene mutations. This syndrome is thought
      to represent a pediatric form of the Cowden syndrome, characterized among other
      features by an increased risk of cancer. We report 5 cases of BRRS, all diagnosed
      in children with lipoma and macrocephaly. Children presenting with lipomas need a
      complete physical examination to look for other signs of BRRS, because they may
      need further follow-up for tumor screening in adulthood.

PMID- 16952600
TI  - Hepatic artery transection after blunt trauma: case presentation and review of
      the literature.
AB  - Hepatic artery injuries sustained as a result of blunt abdominal trauma are rare.
      This case represents the first reported hepatic artery transection and the second
      hepatic artery injury described in children. Hepatic artery injuries are
      associated with high mortality, and their management is complex and
      controversial.

PMID- 16952601
TI  - Nonoperative management of delayed splenic rupture in a patient with hemophilia
      B.
AB  - Nonoperative management of splenic lacerations has become the standard of care in
      hemodynamically stable patients. The decision to manage a patient nonoperatively
      is much more difficult when the patient has a known bleeding disorder. There are
      a few case reports in the literature describing nonoperative management of
      splenic trauma in children with hemophilia A (factor VIII deficiency), but only
      one case report of a patient with hemophilia B (factor IX deficiency) and a
      splenic laceration successfully managed nonoperatively. We present the case of a
      13-year-old boy who presented with a grade 4 splenic laceration, acute blood loss
      anemia, and hypotension that was managed nonoperatively.

PMID- 16952602
TI  - A case of an abdominoscrotal hydrocele surgically treated under laparoscopic
      assistance.
AB  - We herein describe a 9-month-old boy who presented with bilateral scrotal
      hydroceles shortly after birth. The right hydrocele spontaneously resolved during
      this period, and a nonpalpable testis of the right side was noted. In contrast,
      the left hydrocele gradually increased in size. Ultrasound and magnetic resonance
      investigations performed at the age of 7 months could not detect the right testis
      either in the inguinoscrotal region or the abdominal cavity. These examinations
      also pointed out a huge hydrocele that extended from the left scrotum to the
      abdominal cavity. At the age of 9 months, a laparoscopic-assisted operation for
      both the right undescended testis and the left abdominoscrotal hydrocele (ASH)
      was performed. During the operation, an atrophic testis secondary to in utero
      intravaginal torsion was shown on the right inguinal region, and a huge ASH was
      revealed in the left inguinoscrotal region. The finding of the left ASH was
      confirmed by a laparoscope inserted through the processus vaginalis of the right
      side. At first, the processus vaginalis of the left side was highly ligated by
      the inguinal approach, and then the ASH was opened and its wall was resected. Our
      findings suggest that both an understanding of the pathogenesis and a corrective
      operation of ASH can be made via the inguinal approach. In cases associated with
      cryptochidism owing to an intraabdominal testis or an in utero extravaginal
      torsion, a laparoscopic-assisted operation may therefore be useful both for
      making a precise diagnosis and for surgically removing an ASH.

PMID- 16952603
TI  - Self-expanding silicone stent for treatment of postoperative colorectal stricture
      in an infant with Hirschsprung's disease: a case report.
AB  - Benign colorectal strictures can be a complication of intestinal surgery, with
      limited options for endoscopic intervention. In this report, we describe a case
      where a removable silicone stent was temporarily placed to successfully treat a
      benign post operative stricture in an infant with Hirschsprung's disease.

PMID- 16952604
TI  - Suitable age for nasal reconstruction after subtotal amputation in a child, with
      respect to a case involving purpura fulminans.
AB  - The authors report a case of nasal reconstruction in a 5-year-old boy who had
      undergone subtotal amputation of the nose 8 months before in the context of
      meningococcus-induced purpura fulminans. Two-step surgery involved implantation
      of a forehead expansion graft preliminary to use of a contralateral forehead flap
      to cover a cartilaginous graft from the concha that reconstituted the ala nasi,
      columella, and septum. At 1 year of follow-up, the results were considered quite
      satisfactory esthetically and psychologically beneficial. Nasal amputation in the
      child is infrequent, and the procedure is not clearly defined. Early
      reconstruction certainly improves the child's life and social integration. The
      major risk is unsatisfactory growth of the reconstructed nose, which may persuade
      some surgeons to postpone the operation.

PMID- 16952605
TI  - Boerhaave's syndrome in children: a case report and review of the literature.
AB  - Boerhaave's syndrome or spontaneous rupture of the esophagus is a rupture of the
      esophagus after vomiting. It is rare in children, and to date, 26 children have
      been reported. We present the case of a 5-year-old boy who presented with dyspnea
      after vomiting and subcutaneous emphysema. The diagnosis was confirmed with
      esophagoscopy. The patient was successfully treated with a repair of the rupture
      and a fundoplication. We review the literature on Boerhaave's syndrome in
      children.

PMID- 16952606
TI  - Tracheomalacia in esophageal atresia. Usefulness of preoperative imaging
      evaluation for tailored surgical correction.
AB  - Tracheomalacia (TM) associated with esophageal atresia (OA) generally is located
      in the thoracic segment of the trachea, and the close anatomical relationships it
      has with the aortic arch and the other mediastinal structures play a remarkable
      role in the dynamic obstruction of the airways. Only correct preoperative imaging
      studies permit a precise anatomic description of TM, reducing the risk of
      incomplete treatment owing to the persistence of other undervalued problems. This
      report describes the usefulness of preoperative imaging by dynamic fiberoptic
      bronchoscopy and spiral multilayer computed tomography with 3-dimensional
      reconstruction in 7 symptomatic children with segmentary TM associated with
      esophageal atresia and treated surgically "case by case" based on dynamic
      fiberoptic bronchoscopy and computed tomography data.

PMID- 16952611
TI  - Bladder/prostate rhabdomyosarcoma: miles to go before we sleep.

PMID- 16952612
TI  - Shock wave lithotripsy for upper tract stones: refining the algorithm.

PMID- 16952613
TI  - Obesity and erectile dysfunction.

PMID- 16952614
TI  - Bladder/prostate rhabdomyosarcoma: past, present and future.
AB  - PURPOSE: The last few decades have witnessed substantial improvement in outcomes
      in children with bladder/prostate rhabdomyosarcoma. We reviewed relevant
      historical aspects of treatment, current treatment strategies and new
      developments. Most importantly we identified areas of existing controversy, which
      will provide direction for future studies and continued improvements in therapy.
      MATERIALS AND METHODS: A database (PubMed, MEDLINE, etc) search was performed
      from 1966 through January 2005. Approximately 500 citations were identified.
      Relevant citations were reviewed in detail. RESULTS: While the reported cure rate
      has improved to approximately 70% to 80% and bladder preservation rates as high
      as 60% are reported, substantial controversy continues in certain areas.
      Specifically the long-term function of preserved bladders, the contribution of
      radiotherapy to bladder dysfunction, the timing of reconstruction and molecular
      markers of disease progression are among the areas that require further
      investigation. CONCLUSIONS: Substantial progress has been made as a result of
      multi-institutional collaborative trials. Future combined studies are required to
      further the treatment of this childhood malignancy.

PMID- 16952615
TI  - Metastatic prostate cancer-does treatment of the primary tumor matter?
AB  - PURPOSE: In recent years there has been increased interest in adjuvant therapy
      for prostate cancer. This trend has engendered a tendency toward overlooking the
      issue of therapy to the primary tumor in advanced disease. We reviewed the effect
      of treating the principal disease bulk on overall treatment outcome in patients
      with advanced and metastatic cancer. Specifically we evaluated the role of
      surgical tumor cytoreduction. MATERIALS AND METHODS: We performed a comprehensive
      literature review to evaluate the role of surgical debulking on the outcome of
      advanced cancer, including any published evidence supporting a benefit of this
      therapy for prostate cancer. RESULTS: Even in cancers for which adjuvant
      chemotherapy and radiation are used liberally there is a clear benefit to optimal
      surgical debulking for local control and survival. The beneficial role of maximal
      surgical cytoreduction has been clearly demonstrated in advanced ovarian cancer
      and gastrointestinal carcinomatosis. Maximal debulking of brain, liver and lung
      metastasis has translated into longer survival. Removal of the primary tumor has
      been proved to increase survival in randomized trials of metastatic renal cell
      cancer. It appears that patients with node positive and possibly metastatic
      prostate cancer have a better response to androgen ablation with surgical removal
      of the gland. CONCLUSIONS: Surgical cytoreduction of cancer results in a more
      favorable and durable response to systemic therapy. It is reasonable to explore
      aggressive surgical therapy for advanced prostate cancer.

PMID- 16952616
TI  - Prevention of benign prostatic hyperplasia disease.
AB  - PURPOSE: We reviewed the evidence that benign prostatic hyperplasia is a
      progressive condition and men at risk for benign prostatic hyperplasia disease
      can be identified, treated and protected to a meaningful extent regardless of
      symptom status. MATERIALS AND METHODS: The MEDLINE database was searched in 4
      areas of interest relating to benign prostatic hyperplasia, including 1)
      progression of clinical manifestations with age, especially in regard to baseline
      symptom status, 2) the incidence of complications due to disease progression, 3)
      the use of predictive factors that may help identify men at risk for disease
      progression and 4) the prevention of benign prostatic hyperplasia disease with
      medical therapy. RESULTS: Tissue changes in the prostate (benign prostatic
      hyperplasia) are inevitable consequences of aging. However, benign prostatic
      hyperplasia disease, which we define as a life altering urinary condition
      requiring medical intervention, is predictable and preventable. Benign prostatic
      hyperplasia disease progression is associated with increasing prostate volume,
      decreasing urinary flow, symptomatic deterioration often to the point of major
      life-style interference and serious complications, eg acute urinary retention and
      the need for surgery. The risk of benign prostatic hyperplasia disease
      progression was found to be directly related to prostate volume and its surrogate
      marker, serum prostate specific antigen, after prostate cancer is excluded. Other
      factors, eg baseline symptoms and the flow rate, were found to be less relevant
      compared with prostate specific antigen greater than 1.5 ng/ml for predicting
      benign prostatic hyperplasia disease morbidity. CONCLUSIONS: Men at risk for
      benign prostatic hyperplasia disease can be identified using prostate specific
      antigen greater than 1.5 ng/ml as a surrogate marker of prostate volume. In men
      at risk with prostate specific antigen greater than 1.5 ng/ml 5alpha-reductase
      inhibitors have potential value for benign prostatic hyperplasia disease
      prevention regardless of symptom status.

PMID- 16952617
TI  - Drug therapy for idiopathic male infertility: rationale versus evidence.
AB  - PURPOSE: About half of all infertile men who seek treatment have no specific
      cause that can be determined for the seminal abnormality. These men are often
      subject to a number of medical therapies with doubtful efficacy. We reviewed the
      rationale on which these therapies are advised and determined whether sufficient
      medical evidence exists to justify their use. MATERIALS AND METHODS: A literature
      search was performed using MEDLINE/PubMed, focusing on publications of the last
      20 years of drug therapies for idiopathic male factor infertility. Therapies for
      specific abnormalities such as hypogonadism were excluded. Basic science, in
      vitro and animal studies suggesting the mechanism of action for male infertility
      were evaluated as the rationale part of the review, while controlled and
      uncontrolled human clinical trials were reviewed as evidence for drug use.
      RESULTS: There is no evidence in support of androgens and gonadotropins for
      enhancing male fertility. These agents may instead act as contraceptives with
      significant side effects. There is insufficient evidence regarding the role of
      antiestrogens, aromatase inhibitors and antioxidants. No drug therapy has proved
      to be clearly beneficial for idiopathic oligoasthenoteratospermia. CONCLUSIONS:
      Drug therapy for idiopathic male infertility is at best empirical. There is no
      clear benefit of using any medication in these patients. Moreover, androgens
      should not be used because they may actually suppress spermatogenesis.

PMID- 16952618
TI  - Max Nitze, the cystoscope and urology.
AB  - PURPOSE: Maximilian Carl-Friedrich Nitze (1848 to 1906) designed the modern
      cystoscope, providing a foundation for urology. MATERIALS AND METHODS: The
      historical literature, including the original writings of Nitze, was reviewed.
      RESULTS: The invention of the cystoscope by Nitze revolutionized endoscopy but
      his true genius lay in his lifelong pursuit of better methods to diagnose and
      treat patients with urological diseases and in teaching others the practical use
      and value of cystoscopy. He also designed the first operating cystoscope, took
      the first endoscopic photographs and published the first textbook in urology.
      CONCLUSIONS: The legacy of discovery of Max Nitze established the specialty of
      urology and a legitimate claim as the father of urology.

PMID- 16952619
TI  - Pathological features of renal neoplasms classified by size and symptomatology.
AB  - PURPOSE: We examined the relationship between tumor size and pathological
      findings in a contemporary series of surgical renal lesions and we characterized
      the relationship of incidental and symptomatic tumors to pathological findings.
      MATERIALS AND METHODS: We retrospectively reviewed the records of patients
      treated surgically for renal lesions suspicious for malignancy between March 2000
      and May 2005. Specimens were examined for a gross and microscopic description.
      Statistical analysis was used to determine the correlation of size and
      symptomatology. RESULTS: A total of 349 renal masses from 331 patients were
      identified. Of the 349 renal masses 56 (16.0%) were benign, 289 (82.8%) were
      renal cell carcinoma and 4 (1.1%) were other malignancies. The percent of
      malignant tumors increased from 72.1% for those less than 2 cm to 93.7% for those
      greater than 7 cm (OR 1.39, 95% CI 1.17 to 1.65). Of the 349 renal masses 258
      (73.9%) were discovered incidentally and 91 (26.1%) were symptomatic. Mean size
      of incidental and symptomatic tumors was 3.7 and 6.2 cm, respectively (p <
      0.001). When comparing T1 incidental and symptomatic tumors, there was no
      significant difference in the overall frequency of malignancy. When comparing T2
      incidental and symptomatic tumors, the groups had similar malignancy rates (90.9%
      and 100%, respectively, p = 0.16). However, symptomatic lesions showed an
      increased incidence of high grade malignancy (78.4% vs 40.9%, p = 0.012).
      CONCLUSIONS: Smaller renal tumors are more likely to be benign or be a lower
      grade of malignancy. T1 renal tumors are more likely to be detected incidentally
      than T2 tumors. When T1 incidental and symptomatic tumors were compared, there
      was no difference between the malignancy rates. However, when T2 incidental and
      symptomatic tumors were compared, symptomatic tumors were more likely to be high
      grade malignancy.

PMID- 16952621
TI  - The influence of clinical and pathological stage discrepancy on cancer specific
      survival in patients treated for renal cell carcinoma.
AB  - PURPOSE: We compared clinical and pathological staging in a contemporary,
      consecutive series of patients treated with partial or radical nephrectomy for
      renal cell carcinoma and we determined the effect of clinical and pathological
      stage discrepancy on outcomes. MATERIALS AND METHODS: We collected retrospective
      clinical, pathological and survival data on 264 consecutive patients with
      clinical T1-3 renal cell carcinoma who were treated with laparoscopic or open
      partial or radical nephrectomy at a single institution from 1994 to 2003.
      RESULTS: Pathological up staging occurred in 44 of 264 patients (17%) patients.
      Of 135 clinical T1 tumors 25 (18.5%) and 18 of 85 (21.2%) clinical T2 tumors were
      pathologically up staged. Patients with clinical T1 and T2 tumors were stratified
      into 2 groups, including those with the same clinical and pathological stage, and
      those with pathological up staging. Mean 5-year recurrence-free survival +/- SD
      for same stage vs pathologically up staged clinical T1 (84.3% +/- 4.4% vs 47.4%
      +/- 11.5%) and clinical T2 (80.0% +/- 6.8% vs 40.7% +/- 13.4%) tumors was
      significantly different (p < 0.0002). Five-year cancer specific survival for same
      stage vs pathologically up staged clinical T1 tumors was significantly different
      (98.5% +/- 1.5% vs 69.7% +/- 11.3%, p = 0.0005), while that for clinical T2
      tumors approached clinical significance (90.9% +/- 5.0% vs 72.7% +/- 13.4%, p =
      0.0501). CONCLUSIONS: Stage discrepancy is common in surgically treated patients
      diagnosed with renal masses and it has a significant impact on clinical outcome.
      Implications of such clinical and pathological stage discrepancy should be
      considered when counseling patients and determining therapeutic approaches.

PMID- 16952624
TI  - Significance of macroscopic tumor necrosis as a prognostic indicator for renal
      cell carcinoma.
AB  - PURPOSE: We investigated the prognostic significance of macroscopic tumor
      necrosis in renal cell carcinoma. MATERIALS AND METHODS: We retrospectively
      analyzed the records of 485 patients who underwent surgical treatment for organ
      confined or metastatic renal cell carcinoma. The presence or absence of tumor
      necrosis was evaluated based on macroscopic description of the tumor, and tumors
      were considered necrotic only if they exhibited more than 10% macroscopic
      necrosis. RESULTS: Macroscopic tumor necrosis was identified in 27% of total
      patients. Patients with macroscopic necrotic renal cell carcinoma were more
      likely to have larger tumor, metastatic disease, higher local stage and higher
      tumor grade (all p < 0.001). Pathological features of microvascular invasion (p =
      0.026) and sarcomatoid differentiation (p = 0.002) along with several laboratory
      findings were also observed to be associated with macroscopic tumor necrosis.
      Among the total subjects those without macroscopic tumor necrosis had
      significantly higher progression-free (p < 0.0001) and disease specific survival
      (p < 0.0001). When survival analysis was limited to nonmetastatic tumors only,
      the same logic applied, which was not the case for the patients with metastatic
      disease (p > 0.05). Among the different histological subtypes of renal cell
      carcinoma, macroscopic tumor necrosis was observed to have a significant impact
      only for the clear cell subtype. In patients with nonmetastatic RCC multivariate
      analysis revealed that macroscopic tumor necrosis (p = 0.004) was an independent
      prognostic predictor of disease specific survival along with pathological T
      stage, tumor grade and tumor size. CONCLUSIONS: Our results suggest that
      macroscopic tumor necrosis may be a reliable prognostic indicator for
      nonmetastatic clear cell renal cell carcinoma which should routinely be examined
      for during pathological analysis.

PMID- 16952623
TI  - Diagnostic and prognostic validity of serum bone turnover markers in metastatic
      renal cell carcinoma.
AB  - PURPOSE: We assessed the diagnostic accuracy of bone markers in the serum of
      patients with renal cell carcinoma to detect bone metastases and evaluate the
      prognostic potential concerning renal cell carcinoma caused mortality. MATERIALS
      AND METHODS: The bone formation markers total and bone specific alkaline
      phosphatase, the bone resorption markers cross-linked N-terminal and tartrate
      resistant acid phosphatase isoenzyme 5b, and the osteoclastogenesis markers
      osteoprotegerin and ligand of the receptor activator of nuclear factor-kappaB,
      were measured in the serum of 72 patients with renal cell carcinoma, including 28
      with pN0M0, 8 with pN1M0 and 36 with M1, and in 32 female and 36 male controls by
      enzyme-linked immunosorbent assay techniques. Data were evaluated by receiver
      operating characteristics and survival analysis. RESULTS: Bone specific alkaline
      phosphatase, tartrate-resistant acid phosphatase isoenzyme 5b and ligand of the
      receptor activator of nuclear factor-kappaB did not significantly differ between
      patients with renal cell carcinoma and controls. Compared with controls tartrate
      resistant acid phosphatase isoenzyme 5b, cross-linked N-terminal and
      osteoprotegerin showed increased concentrations in patients with nonbone
      metastases but not in those with bone metastases. No bone turnover marker led to
      differentiation between patients with nonbone and bone metastases. Increased
      osteoprotegerin above the upper 95% cutoff limit, tumor stage and distant
      metastatic spread were associated with renal cell carcinoma related survival on
      Kaplan-Meier analyses. A multivariate Cox proportional hazards regression model
      revealed that these 3 variables were independent prognostic factors for cancer
      related death. CONCLUSIONS: Bone turnover markers are hardly useful to diagnose
      bone metastases in patients with renal cell carcinoma. However, osteoprotegerin
      together with clinicopathological characteristics may be helpful as
      prognosticator of cancer specific death.

PMID- 16952626
TI  - Temporary renal ischemia during nephron sparing surgery is associated with short
      term but not long-term impairment in renal function.
AB  - PURPOSE: The emergence of laparoscopic nephron sparing surgery has rekindled
      interest in the impact of warm renal ischemia on renal function. To provide data
      with which warm renal ischemia can be compared we analyzed short-term and long
      term changes in the glomerular filtration rate after temporary cold renal
      ischemia. MATERIALS AND METHODS: In patients undergoing open nephron sparing
      surgery the estimated glomerular filtration rate was assessed preoperatively,
      early in the postoperative hospital stay, and 1 and 12 months after surgery using
      the abbreviated Modification of Diet in Renal Disease Study equation. We
      separately analyzed 70 patients with a solitary kidney and 592 with 2 functioning
      kidneys. The end point was the percent change from the baseline glomerular
      filtration rate. A linear regression model was used to test the association
      between the glomerular filtration rate change, and ischemia time, patient age,
      tumor size, estimated blood loss and intraoperative fluid administration.
      RESULTS: Median cold ischemia time was 31 minutes in patients with a solitary
      kidney and 35 minutes in those with 2 kidneys. Compared to patients with 2
      kidneys those with a solitary kidney had a significantly lower preoperative
      estimated glomerular filtration rate (p < 0.001), which decreased a median of 30%
      during the early postoperative period, and 15% and 32% 1 and 12 months after
      surgery, respectively. In patients with 2 kidneys the corresponding glomerular
      filtration rate decreases were 16%, 13% and 14%, respectively. On multivariate
      analyses in each group cold ischemia duration and intraoperative blood loss were
      significantly associated with early glomerular filtration rate changes. However,
      12 months after surgery age was the only independent predictor of a glomerular
      filtration rate decrease in patients with 2 kidneys. CONCLUSIONS: Cold renal
      ischemia during nephron sparing surgery is a significant determinant of the short
      term postoperative glomerular filtration rate. Longer clamping time is
      particularly detrimental in patients with a solitary kidney but it does not
      appear to influence long-term renal function. Patients of advanced age may be
      less likely to recover from acute ischemic renal injury.

PMID- 16952628
TI  - Phase I/II pilot study of intravesical apaziquone (EO9) for superficial bladder
      cancer.
AB  - PURPOSE: The quinone based bioreductive drug apaziquone (EO9) failed to
      demonstrate efficacy in previous phase II studies following intravenous
      administration. We determined the dose of apaziquone that can be safely
      administered intravesically and explored its activity for superficial bladder
      transitional cell carcinoma. MATERIALS AND METHODS: Six patients with multifocal,
      Ta/T1 and G1/G2 transitional cell carcinoma of the bladder received escalating
      doses of apaziquone formulated as EOquintrade mark (0.5 mg/40 ml up to 16 mg/40
      ml) weekly for 6 weeks. A further 6 patients received weekly apaziquone at the
      highest nontoxic dose established. Pharmacokinetic parameters were determined in
      urine and blood, and the pharmacodynamic markers NQO1 (reduced nicotinamide
      adenine dinucleotide phosphate:quinone oxidoreductase-1) and glucose transporter
      1 were also characterized. Efficacy was determined against a marker lesion.
      RESULTS: Local toxicity (grades 2 and 3 dysuria, and hematuria) was observed at
      doses of 8 mg/40 ml and above but 4 mg/40 ml was well tolerated with no systemic
      or local side effects. Apaziquone in urine increased linearly with the dose but
      no apaziquone was detected in plasma. In 8 of 12 patients complete macroscopic
      and histological disappearance of the marker lesion occurred. A correlation
      between response and NQO1 and/or glucose transporter 1 expression could not be
      established. CONCLUSIONS: Intravesical administration of 4 mg/40 ml apaziquone
      was well tolerated and had ablative activity against superficial bladder cancer
      marker lesions.

PMID- 16952629
TI  - Phase II marker lesion study with intravesical instillation of apaziquone for
      superficial bladder cancer: toxicity and marker response.
AB  - PURPOSE: We studied the ablative activity of intravesical apaziquone (EOquin) on
      a papillary marker tumor and determined the incidence of side effects. MATERIALS
      AND METHODS: A total of 46 patients with multiple pTa or pT1 bladder tumors
      underwent visible lesion resection except for 1 marker tumor. Patients were then
      treated with 6 instillations of apaziquone at weekly intervals. The response was
      determined 2 to 4 weeks after the last instillation. RESULTS: One patient
      withdrew informed consent and refused the last treatment due to side effects. A
      histologically proven complete response was seen in 30 patients. Progression to
      invasive stage was not observed. Local side effects in this study were comparable
      to those due to other chemotherapy instillations, such as mitomycin C and
      epirubicin, but less severe and less frequent compared to those of bacillus
      Calmette-Guerin instillations. CONCLUSIONS: The histological complete response
      rate after 6 consecutive instillations of apaziquone in patients with superficial
      bladder cancer was 67% (95% CI 51 to 80). Local side effects were comparable to
      side effects due to other chemotherapy instillations.

PMID- 16952631
TI  - Nomogram for predicting disease recurrence after radical cystectomy for
      transitional cell carcinoma of the bladder.
AB  - PURPOSE: American Joint Committee on Cancer staging represents the gold standard
      for prediction of recurrence after radical cystectomy in patients with invasive
      bladder cancer. We tested the hypothesis that American Joint Committee on Cancer
      stage based predictions may be improved when pathological tumor and node stage
      information is combined with additional clinical and pathological variables
      within a prognostic nomogram. MATERIALS AND METHODS: We used Cox proportional
      hazards regression analysis to model variables of 728 patients with transitional
      cell carcinoma of the bladder treated with radical cystectomy and bilateral
      pelvic lymphadenectomy at 1 of 3 participating institutions. Standard predictors,
      pT and pN, were complemented by age, gender, tumor grade at cystectomy, presence
      of lymphovascular invasion, presence of carcinoma in situ in the cystectomy
      specimen, neoadjuvant chemotherapy, adjuvant chemotherapy and adjuvant
      radiotherapy. The concordance index was used to quantify the accuracy of
      regression coefficient based nomograms. A total of 200 bootstrap resamples were
      used to reduce overfit bias and for internal validation. Calibration plots were
      used to graphically explore the performance characteristics of the multivariate
      nomogram. RESULTS: Followup ranged from 0.1 to 183.4 months (median 24.9, mean
      36.4). Recurrence was recorded in 249 (34.2%) patients with a median time to
      recurrence of 108 months (range 0.8 to 131.9). Actuarial recurrence-free
      probabilities were 69.6% (95% CI 65.8%-73.0%), 60.2% (55.8%-64.3%) and 52.9%
      (47.3%-58.1%) at 2, 5 and 8 years after cystectomy, respectively. Two-hundred
      bootstrap corrected predictive accuracy of American Joint Committee on Cancer
      stage based predictions was 0.748. Accuracy increased by 3.2% (0.780) when age,
      lymphovascular invasion, carcinoma in situ, neoadjuvant chemotherapy, adjuvant
      chemotherapy and adjuvant radiotherapy were added to pathological stage
      information and used within a nomogram. CONCLUSIONS: A nomogram predicting
      bladder cancer recurrence after cystectomy is 3.2% more accurate than American
      Joint Committee on Cancer stage based predictions. Moreover, a nomogram approach
      combines several advantages such as easy and precise estimation of individual
      recurrence probability at key points after cystectomy, which all patients deserve
      to know and all treating physicians need to know.

PMID- 16952633
TI  - The effects of adjusting for case mix on mortality and length of stay following
      radical cystectomy.
AB  - PURPOSE: Prior studies evaluating quality of care following radical cystectomy
      have been constrained by the use of retrospective reviews of single institutional
      series and limited ability to examine risk factors in a comprehensive manner.
      Characterization of these factors could enhance preoperative patient counseling
      and facilitate perioperative management, thereby improving the quality of patient
      care. MATERIALS AND METHODS: The National Surgical Quality Improvement Project is
      a prospective quality management initiative at 123 Veterans Affairs Medical
      Centers nationwide. The project collects preoperative clinical and intraoperative
      data, and outcomes on a wide variety of surgical procedures from multiple
      surgical disciplines. Since 1991, 2,538 radical cystectomies have been captured
      by the National Surgical Quality Improvement Project. Modeling using logistic
      regression was performed to identify preoperative risk factors associated with
      mortality and prolonged length of stay (greater than 90th percentile) after
      radical cystectomy. RESULTS: The 30 and 90-day mortality rates following
      cystectomy were 2.9% and 6.8%, respectively, and median hospital stay was 11 days
      (90th percentile 30). Robust preoperative factors associated with mortality and
      prolonged length of stay that uniformly increased risk were older patient age (OR
      1.2 to 1.4), American Society of Anesthesiologists class 3 or greater (OR 1.5 to
      3.3), dependent functional status (OR 1.7 to 2.0) and low serum albumin (OR 2.1
      to 12.0). CONCLUSIONS: A defined set of preoperative risk factors is
      independently associated with greater mortality and hospital stay following
      radical cystectomy. The breadth of these factors suggests that complex case mix
      adjustment is mandatory when comparing outcomes. Implementation of novel
      processes directed toward minimizing patient risk has the potential to improve
      outcomes following cystectomy.

PMID- 16952635
TI  - Combination of oral tramadol, acetaminophen and 1% lidocaine induced
      periprostatic nerve block for pain control during transrectal ultrasound guided
      biopsy of the prostate: a prospective, randomized, controlled trial.
AB  - PURPOSE: Prostate biopsy for diagnosing cancer can be painful. Tramadol is a
      centrally acting analgesic used to treat many pain disorders. We determined
      whether administering oral tramadol and acetaminophen combined with 1% lidocaine
      induced periprostatic nerve block would significantly decrease the pain
      experienced by patients during standard 10-core transrectal ultrasound guided
      needle biopsy of the prostate. MATERIALS AND METHODS: A total of 60 men who
      presented for diagnostic prostate biopsy were randomized to receive placebo plus
      periprostatic 1% lidocaine as the control group of 30 or 75 mg tramadol/650 mg
      acetaminophen orally plus periprostatic 1% lidocaine as the experimental group of
      30 before undergoing biopsy. Immediately after biopsy each patient was asked to
      rate the pain on a linear 10-point scale and a standard 6-point faces pain scale.
      Complications of pain medication administration in each group were noted and
      compared. RESULTS: Pain medication administration was well tolerated by each
      study group except for lightheadedness/dizziness and itching in 1 patient each in
      the experimental group, and lightheadedness/dizziness in 1 patient in the control
      group. Overall patients in the experimental group reported a mean decrease +/- SD
      in the pain score of 2.3 +/- 2.4 on the scale of 1 to 10 (p = 0.0008) and 1.11 +/
      1.25 on the scale of 0 to 5 compared with scores in controls (p = 0.0009).
      CONCLUSIONS: Administering 75 mg tramadol/650 mg acetaminophen orally with
      periprostatic 1% lidocaine before transrectal ultrasound guided prostate biopsy
      is a safe, easy and effective method of controlling pain during the biopsy
      procedure.

PMID- 16952636
TI  - Re-biopsy of the prostate using a stereotactic transperineal technique.
AB  - PURPOSE: In this study we investigated the detection rate and morbidity of
      stereotactic transperineal prostate re-biopsy with 3-dimensional mapping for
      diagnosis of nonpalpable isoechoic occult prostate malignancy. MATERIALS AND
      METHODS: A total of 180 consecutive patients with continued increasing total
      prostate specific antigen and at least 1 prior benign transrectal prostate biopsy
      underwent stereotactic transperineal prostate biopsy at a single outpatient
      institution between April 2004 and March 2006. Similar to a prostate
      brachytherapy procedure, patients were placed in the dorsal lithotomy position.
      With the patient under general anesthesia, and using transrectal ultrasound, a
      perineal brachytherapy template and stabilizing device, the prostate was
      positioned on the implant grid. It was equally divided into 8 sections (octants)
      according to x and y coordinates on the mid gland axial image. The midplanes of
      axial and sagittal prostate gland images for each patient determined the x, y and
      z coordinates that would occupy each octant. Tissue cores were initially obtained
      from the apical octants, followed by identical x and y coordinates of the basilar
      octants. Specimens from each specific octant were placed in 1 of 8 specimen jars
      and pathological review was reported accordingly. RESULTS: Stereotactic
      transperineal prostate biopsy yielded positive biopsies identifying
      adenocarcinoma in 68 of 180 (38%) patients. Acute urinary retention developed in
      18 of 180 (10%) patients requiring an indwelling urinary catheter upon discharge
      home. In all patients estimated blood loss was less than 5 cc and median pain
      score was 1 of 10. CONCLUSIONS: Stereotactic transperineal prostate biopsy is
      extremely well tolerated and useful for diagnosis of nonpalpable isoechoic occult
      prostate malignancy. Additionally, stereotactic transperineal prostate biopsy
      provides comprehensive tissue sampling with accurate 3-dimensional mapping of
      malignancy in this select group of patients.

PMID- 16952638
TI  - Changing patterns of pelvic lymphadenectomy for prostate cancer: results from
      CaPSURE.
AB  - PURPOSE: Widespread screening for prostate cancer in the United States has
      resulted in earlier tumor identification at lower stages. The fewer number of men
      with lymph node metastases at initial presentation has altered patterns of pelvic
      lymphadenectomy before definitive treatment. We characterized patterns of pelvic
      lymphadenectomy in conjunction with radical prostatectomy in a community based
      cohort. MATERIALS AND METHODS: In the CaPSURE database we identified men
      undergoing radical prostatectomy. Patients were stratified into 3 clinical risk
      groups based on serum prostate specific antigen, T stage and pathological grade.
      We examined temporal trends of pelvic lymphadenectomy and predictors of pelvic
      lymphadenectomy. RESULTS: From 1992 to 2004 the proportion of men undergoing
      pelvic lymphadenectomy in conjunction with radical prostatectomy decreased from
      94% to 80%. Overall positive lymph nodes were identified in 0.87%, 2.0% and 7.1%
      of men in the low, intermediate and high risk groups, respectively. While men
      with high risk disease continued to undergo pelvic lymphadenectomy at a high rate
      (greater than 90%), the fraction of men at low and intermediate risk undergoing
      pelvic lymphadenectomy steadily decreased. Prostate specific antigen, Gleason
      sum, clinical stage and income were factors associated with pelvic
      lymphadenectomy. A mean of 5.7 lymph nodes (median 5.0) were removed.
      CONCLUSIONS: The performance of pelvic lymphadenectomy has decreased in patients
      at low and intermediate risk, and remained stable in patients at high risk.
      Further investigation of the role of extended pelvic lymphadenectomy and the
      potential therapeutic benefits of pelvic lymphadenectomy would better define the
      contemporary role of pelvic lymphadenectomy and identify appropriate candidates.

PMID- 16952639
TI  - Association between the dihydrotestosterone level in the prostate and prostate
      cancer aggressiveness using the Gleason score.
AB  - PURPOSE: To our knowledge the association between dihydrotestosterone in the
      prostate and prostate cancer aggressiveness has not yet been elucidated. We
      analyzed dihydrotestosterone levels in the prostate and Gleason score in patients
      diagnosed with clinically localized prostate cancer. MATERIALS AND METHODS: A
      total of 81 patients with suspected prostate cancer underwent prostate biopsy.
      Serum samples were collected before biopsy. Dihydrotestosterone levels in
      prostatic tissue and serum were analyzed using liquid chromatography/electrospray
      ionization-mass spectrometry after polar derivatization. RESULTS: A total of 47
      patients were diagnosed with stages T1 to T3N0M0 prostate cancer and 34 were
      diagnosed with no malignancy. Of the 47 patients 32 had a Gleason score of 6 or
      less and 15 had a score of 7 to 10. Dihydrotestosterone in prostatic tissue in
      patients with Gleason score 7 to 10 disease was significantly lower than in those
      with Gleason score 6 or less disease (p = 0.025). Gleason score correlated with
      the testosterone-to-serum dihydrotestosterone ratio (rs = 0.329, p = 0.038).
      CONCLUSIONS: Patients with Gleason score 7 to 10 prostate cancer have low
      dihydrotestosterone in the prostate, although there were no significant
      differences between patients with Gleason score 7 to 10 vs 6 or less prostate
      cancer with respect to serum androgens. Low dihydrotestosterone in cases of
      aggressive prostate cancer is probably sufficient to activate androgen receptor
      expression and propagate tumor growth.

PMID- 16952640
TI  - Modeling prostate specific antigen kinetics in patients on active surveillance.
AB  - PURPOSE: Prostate specific antigen doubling time was used to stratify patients
      into groups at low and high risk for progression. The prostate specific antigen
      kinetics in these 2 groups were modeled. MATERIALS AND METHODS: In this
      prospective, single-arm cohort study patients with favorable clinical parameters
      (stage T1b-T2b N0M0, Gleason score 7 or less, prostate specific antigen 15 ng/ml
      or less) were conservatively treated with watchful waiting. Evolution of serial
      prostate specific antigen measurements over time was estimated from a general
      linear mixed model of the natural log of prostate specific antigen. The
      corresponding average and individual prostate specific antigen doubling times
      were also calculated. RESULTS: Since November 1995 a total of 231 patients had at
      least 6 months of followup and at least 3 prostate specific antigen measurements.
      Based on prostate specific antigen doubling time and repeat biopsy, 93 patients
      fulfilled the criteria for high risk of disease progression and 138 were defined
      as low risk. Given the baseline status of these individuals, 2 reference average
      lines (high risk and low risk) were derived to model the evolution of prostate
      specific antigen levels and permit more rational decision making regarding the
      need for definitive intervention. The average prostate specific antigen doubling
      time was 2.97 years (95% CI 2.2-4.4) in patients allocated to the high risk group
      and 6.54 years (95% CI 4.8-12.3) in those at low risk. CONCLUSIONS: By applying
      the dynamic prognostic rule in combination with serial biopsy, a rational
      decision for definitive intervention based on the risk of disease progression
      could be optimally recommended about 2.3 years after initiated surveillance.

PMID- 16952643
TI  - Prediagnosis prostate specific antigen velocity is associated with risk of
      prostate cancer progression following brachytherapy and external beam radiation
      therapy.
AB  - PURPOSE: Prostate specific antigen velocity 2.0 ng/ml per year or greater in the
      year before prostate cancer diagnosis is associated with cancer specific survival
      following radical prostatectomy and radiation therapy. We evaluated the
      relationship between prediagnosis prostate specific antigen velocity and cancer
      progression following primary radiation therapy. MATERIALS AND METHODS: We
      analyzed the records of 24,893 men from a community based prostate cancer
      screening study and identified 237 with clinically localized prostate cancer who
      elected primary radiation therapy. Our final cohort consisted of 130 men,
      including 83 treated with external beam radiation and 47 treated with
      brachytherapy. Patient specific variables at diagnosis were analyzed for their
      value in predicting biochemical progression using American Society for
      Therapeutic and Radiation Oncology criteria. RESULTS: Mean followup +/- SD was 64
      +/- 35 months. Prostate specific antigen at diagnosis, family history of prostate
      cancer and prediagnosis prostate specific antigen velocity 2.0 ng/ml per year or
      greater were associated with cancer progression following brachytherapy or
      external beam radiation. Of men with prostate specific antigen velocity 2.0 ng/ml
      per year or greater 38% had cancer progression compared to 12% with prostate
      specific antigen velocity less than 2.0 ng/ml per year (OR 4.3, p = 0.003). The 6
      year progression-free survival estimate was 57% in men with prostate specific
      antigen velocity 2.0 ng/ml per year or greater and 82% in men with prostate
      specific antigen velocity less than 2.0 ng/ml per year (p < 0.001). On
      multivariate analysis absolute prostate specific antigen at diagnosis and
      prostate specific antigen velocity 2.0 ng/ml per year or greater were
      independently associated with cancer progression in men treated with external
      beam radiation therapy or brachytherapy. CONCLUSIONS: Men with a prediagnosis
      prostate specific antigen velocity of 2.0 ng/ml per year or greater are at
      increased risk for cancer progression following brachytherapy or external beam
      radiation compared to men with a prostate specific antigen velocity of less than
      2.0 ng/ml per year.

PMID- 16952644
TI  - Time to prostate specific antigen recurrence after radical prostatectomy and risk
      of prostate cancer specific mortality.
AB  - PURPOSE: In patients treated with radical prostatectomy who have biochemical
      recurrence we have previously reported that time from surgery to biochemical
      recurrence and postoperative prostate specific antigen doubling time are
      significantly related to the risk of prostate cancer death. We performed a more
      thorough examination of the association of time from surgery to biochemical
      recurrence and the risk of prostate cancer death. MATERIALS AND METHODS: We
      retrospectively studied the records of 379 patients treated with radical
      prostatectomy between 1982 and 2000 who had had biochemical recurrence. We
      examined the association of time from surgery to prostate specific antigen
      recurrence and prostate specific antigen doubling time, and the risk of prostate
      cancer death using the Spearman correlation and Cox proportional hazards
      regression, respectively. RESULTS: Longer time from surgery to prostate specific
      antigen recurrence was associated with a slower prostate specific antigen
      doubling time (Spearman r = 0.36, p < 0.001) and a decreased risk of prostate
      cancer death (RR 0.76, 95% CI 0.66 to 0.88, p < 0.001). The 15-year actuarial
      prostate cancer specific survival rate after biochemical recurrence in patients
      with recurrence at 3 years or less was 41% (95% CI 29 to 53) compared to 87% (95%
      CI 75 to 93) in patients with recurrence more than 3 years after radical
      prostatectomy. On multivariate analysis a shorter time from surgery to prostate
      specific antigen recurrence was associated with an increased risk of prostate
      cancer death (3 or less vs more than 3 years, RR 2.70, 95% CI 1.37 to 5.31, p =
      0.004). CONCLUSIONS: Earlier prostate specific antigen recurrence is associated
      with an increased risk of prostate cancer death. These data suggest that perhaps
      time to prostate specific antigen recurrence may be a reasonable intermediate end
      point in patients treated with radical prostatectomy, although this must be
      validated in other studies.

PMID- 16952645
TI  - E-cadherin protein expression predicts prostate cancer salvage radiotherapy
      outcomes.
AB  - PURPOSE: Radiotherapy for biochemical prostate cancer recurrence after
      prostatectomy achieves durable salvage rates of only 40% to 50%. Improved methods
      of identifying patients unlikely to benefit from salvage radiotherapy are needed.
      Altered expression of the adhesion molecule E-cadherin may be associated with the
      invasive and metastatic phenotype. We examined the relationship between E
      cadherin expression and outcomes after salvage radiotherapy. MATERIALS AND
      METHODS: E-cadherin expression was examined by immunohistochemistical analysis of
      a tissue microarray of prostatectomy tissues from patients who underwent salvage
      radiotherapy. The relation between E-cadherin staining, other risk factors and
      biochemical failure after salvage radiotherapy was analyzed using Kaplan-Meier
      and Cox regression methods. RESULTS: Of 37 analyzable cases 25 showed aberrant E
      cadherin expression, while the remainder had normal expression. At a median
      clinical followup of 40 months univariate analysis demonstrated that E-cadherin
      staining was not associated with Gleason score, extracapsular extension, surgical
      margin status, pre-prostatectomy or pre-radiotherapy prostate specific antigen,
      complete biochemical response after radiotherapy or adjunctive hormonal therapy
      but it was associated with seminal vesicle invasion. Two-year failure-free
      survival was 55% in patients with aberrant E-cadherin expression compared with
      92% in patients with normal E-cadherin expression (p = 0.02). Multivariate
      analysis confirmed that aberrant E-cadherin expression was associated with
      salvage radiotherapy failure (p = 0.03). CONCLUSIONS: Aberrant E-cadherin
      staining is associated with increased biochemical failure rates after salvage
      radiotherapy. Patients with biochemical failure after prostatectomy and aberrant
      E-cadherin expression are likely to have subclinical disseminated disease. Early
      systemic therapy may be warranted in these patients.

PMID- 16952647
TI  - Long-term outcome of high dose intensity modulated radiation therapy for patients
      with clinically localized prostate cancer.
AB  - PURPOSE: We report on the long-term results and late toxicity outcomes of high
      dose intensity modulated radiation therapy for patients with clinically localized
      prostate cancer. MATERIALS AND METHODS: Between 1996 and 2000 a total of 561
      patients with clinically localized prostate cancer were treated with intensity
      modulated radiation therapy. All patients were treated to a dose of 81 Gy
      prescribed to the planning target volume. Prostate specific antigen relapse was
      defined according to the American Society for Therapeutic Radiology and Oncology
      consensus and Houston definitions (absolute nadir plus 2 ng/ml dated at the
      call). Median followup was 7 years (range 5 to 9). RESULTS: The 8-year actuarial
      PSA relapse-free survival rates for patients in favorable, intermediate and
      unfavorable risk groups according to the American Society for Therapeutic
      Radiology and Oncology definition were 85%, 76% and 72%, respectively (p <0.025).
      The 8-year actuarial prostate specific antigen relapse-free survival rates for
      patients in favorable, intermediate and unfavorable risk groups according to the
      Houston definition were 89%, 78% and 67%, respectively (p = 0.0004). The 8-year
      actuarial likelihood of grade 2 rectal bleeding was 1.6%. Three patients (0.1%)
      experienced grade 3 rectal toxicity requiring either 1 or more transfusions or a
      laser cauterization procedure. No grade 4 rectal complications have been
      observed. The 8-year likelihood of late grade 2 and 3 (urethral strictures)
      urinary toxicities were 9% and 3%, respectively. Among patients who were potent
      before intensity modulated radiation therapy, erectile dysfunction developed in
      49%. The cause specific survival outcomes for favorable, intermediate and
      unfavorable risk cases were 100%, 96% and 84%, respectively. CONCLUSIONS: These
      long-term results confirm our previous observations regarding the safety of high
      dose intensity modulated radiation therapy for clinically localized prostate
      cancer. Despite the application of high radiation doses, the incidence of rectal
      bleeding at 8 years was less than 2%. Despite the increased conformality of the
      dose distribution associated with intensity modulated radiation therapy,
      excellent long-term tumor control outcomes were achieved.

PMID- 16952648
TI  - Time to return to work and physical activity following open radical retropubic
      prostatectomy.
AB  - PURPOSE: We identified factors that predict return to part-time and full-time
      work and resumption of unlimited physical activity following open radical
      retropubic prostatectomy. MATERIALS AND METHODS: Between July 1, 2002 and
      February 28, 2005, 537 men with clinically localized prostate cancer underwent
      open radical retropubic prostatectomy, as performed by a single surgeon.
      Intraoperative, perioperative and postoperative parameters were recorded in real
      time and entered into a database. An assessment was made 1 and 3 months
      postoperatively regarding time to return to work and unrestricted physical
      activity. RESULTS: Of the men 50% returned to part-time and full-time work, and
      unrestricted activity within 14, 21 and 30 days after discharge home,
      respectively. Patient age and hematocrit at hospital discharge significantly
      predicted return to part-time and full-time work, and unlimited physical
      activity. The number of days that the urinary catheter was indwelling was also
      associated with return to part-time work. Occupation (blue vs white collar) and
      marital status were also associated with return to full-time work. In the
      multivariate model a unit increase in hematocrit decreased the time to return to
      part-time and full-time work, and unrestricted physical activity by 0.50, 0.60
      and 0.59 days, respectively. Men with discharge hematocrit greater than 32% were
      1.57 (p = 0.059), 1.65 (p = 0.041) and 2.03 (p = 0.002) times more likely to
      return to part-time and full-time work, and unlimited activity before 14, 21 and
      30 days, respectively. Overall models were developed that accounted for 9.4%,
      14.0% and 4.0% of the time to return to part-time work, full-time work and
      unrestricted physical activity, respectively. CONCLUSIONS: Efforts to increase
      discharge hematocrit by minimizing intraoperative blood loss or using
      preoperative blood management strategies and earlier removal of the urinary
      catheter have a favorable impact on the return to work and physical activity.

PMID- 16952649
TI  - Outcomes of surveillance protocol of clinical stage I nonseminomatous germ cell
      tumors-is shift to risk adapted policy justified?
AB  - PURPOSE: We evaluated the potential risk factors for disease relapse in patients
      with clinical stage I nonseminomatous germ cell tumors treated with surveillance
      and reevaluated our treatment of these patients. MATERIALS AND METHODS: A total
      of 211 consecutive patients with clinical stage I nonseminomatous germ cell
      tumors treated with surveillance after orchiectomy between 1993 and 2005 were
      included in this retrospective study. Risk factors evaluated were presence of
      vascular invasion, proportion of embryonal carcinoma, age, tumor size,
      preoperatively increased serum alpha-fetoprotein and the absence of yolk sac
      component. RESULTS: Of the 211 patients 66 (31.3%) had disease relapse.
      Recurrence ranged from 2 to 32 months after orchiectomy (median 6). A total of 52
      (78.8%) cases of relapse were diagnosed in year 1 of followup, 11 (16.7%) during
      year 2 and only 3 cases were diagnosed thereafter. The first evidence of relapse
      was most commonly the increase in serum tumor markers alone (28.8%) or in
      combination with other modalities (66.7%, overall 95.5%). While 40.9% of patients
      with more than 50% embryonal carcinoma had disease relapse, the relapse rate was
      20.8% in patients with less than 50% embryonal carcinoma (p = 0.002). Relapse
      rates in patients with and without vascular invasion were 75.5% and 17.9%,
      respectively (p = 0.000). The relapse rates were 6.1% and 75.7% in patients with
      no risk factors (no vascular invasion and less than 50% embryonal carcinoma) and
      2 risk factors (vascular invasion and more than 50% embryonal carcinoma),
      respectively (p < 0.001). Multivariate analysis revealed that vascular invasion
      was the most powerful predictor of relapse (OR 16.350, 95% CI 5.582-47.893).
      Disease-free and disease specific survival rates were 97.6% at a median followup
      of 75 months. CONCLUSIONS: In light of our results we suggest that all patients
      with vascular invasion should receive chemotherapy. However, patients with no
      risk factors and those with more than 50% embryonal carcinoma but without
      vascular invasion should be on surveillance after orchiectomy since the relapse
      rate is less than 30%. Although strict followup in the first year is justified,
      followup schemas may be reassessed for the frequency of radiological
      investigations.

PMID- 16952652
TI  - Predicting regional lymph node metastasis in Chinese patients with penile
      squamous cell carcinoma: the role of histopathological classification, tumor
      stage and depth of invasion.
AB  - PURPOSE: We determined whether histological factors of primary penile squamous
      cell carcinoma could predict the risk of regional lymph node metastasis.
      MATERIALS AND METHODS: The clinical records of 72 consecutive Chinese patients
      with squamous cell carcinoma of the penis were analyzed retrospectively. Of the
      patients 58 underwent bilateral inguinal lymph node dissection, of whom 9 also
      underwent unilateral or bilateral pelvic lymph node dissection. Primary lesions
      were evaluated according to recently revised standards. The variables recorded
      were histopathological classification, histological grade, pathological tumor
      stage, invasion depth, vascular invasion, and the number and position of
      metastatic lymph nodes. RESULTS: No patients with verrucous carcinoma had
      regional lymph node metastasis. However, 100% of patients with basaloid, 33.3%
      with warty and 30% with typical squamous cell carcinoma had lymph node metastasis
      (p = 0.002). The rate of lymph node metastasis was 18.8% in patients with pT1, as
      compared with 53.1% in patients with pT2 or pT3 (p = 0.004). The mean depth of
      invasion was 9.3 (range 2 to 22) vs 3.2 mm (range 1 to 6) in patients with and
      without lymph node metastasis, respectively (p < 0.001). CONCLUSIONS:
      Histopathological classification, pathological tumor stage and depth of invasion
      of the primary lesion are significant predictors of regional lymph node
      metastasis in Chinese patients with penile squamous cell carcinoma. Combining
      these predictors can be used to select patients who are the best candidates for
      regional lymphadenectomy.

PMID- 16952654
TI  - Safety and efficacy of hyperbaric oxygen therapy for the treatment of
      interstitial cystitis: a randomized, sham controlled, double-blind trial.
AB  - PURPOSE: We conducted a double-blind, sham controlled study to evaluate the
      safety, efficacy and feasibility of hyperbaric oxygenation for interstitial
      cystitis. MATERIALS AND METHODS: A total of 21 patients with interstitial
      cystitis were randomized to 90 minutes treatment in a hyperbaric chamber
      pressurized with 100% O2 to 2.4 atmosphere absolute for 30 treatments sessions or
      1.3 atmosphere absolute, breathing normal air in the control group. Moderate or
      marked improvement in a global response assessment questionnaire was defined as
      treatment response (primary outcomes). Secondary measurements included changes of
      pain and urgency evaluated by visual analog scales, functional bladder capacity
      and frequency. Changes in the O'Leary-Sant Interstitial Cystitis Index and rating
      of overall satisfaction with the therapeutic outcome were also reported. RESULTS:
      There were 3 of 14 patients on verum and no control patients who were identified
      as responders (p < 0.52) [corrected] At 12-month followup 3 patients (21.4%)
      still reported treatment response. Hyperbaric oxygenation resulted in a decrease
      of baseline urgency intensity from 60.2 +/- 15.0 to 49.9 +/- 35.2 mm at 3 months
      and decrease of pain intensity from 43.1 +/- 20.5 to 31.2 +/- 19.8 mm,
      respectively (p < 0.05). The Interstitial Cystitis Symptom Index score sum
      decreased from 25.7 to 19.9 points in patients on verum. Sham treatment did not
      result in improvement of the baseline parameters. CONCLUSIONS: A total of 30
      treatment sessions of hyperbaric oxygenation appear to be a safe, effective and
      feasible therapeutic approach to interstitial cystitis. In the treatment
      responders application of hyperbaric oxygenation resulted in a sustained decrease
      of interstitial cystitis symptoms with a discordant profile regarding the peak
      amelioration of the various interstitial cystitis symptoms compared with a
      normobaric, normoxic sham treatment.

PMID- 16952655
TI  - Extracorporeal shock wave lithotripsy for large ureteral stones using HM3
      lithotriptor.
AB  - PURPOSE: We assessed the efficacy of extracorporeal shock wave lithotripsy for
      large (more than 10 mm) ureteral calculi with the unmodified Dornier HM3
      lithotriptor. MATERIALS AND METHODS: A total of 96 consecutive patients with
      large ureteral stones were treated with shock wave lithotripsy using an
      unmodified HM3 lithotriptor. Patients, stone characteristics, preliminary
      treatment before shock wave lithotripsy, additional procedures after shock wave
      lithotripsy, complications and clinical outcomes were assessed. RESULTS: Between
      2000 and 2003 a total of 96 patients (75 males, 21 females, mean age 51 years
      [range 16 to 81]) with large ureteral stones underwent shock wave lithotripsy.
      Average stone size was 14 mm (range 10 to 22), 90 stones were calcified, and 66
      stones were located in the upper ureter, 20 in the mid ureter and 10 in the
      distal ureter. A total of 77 (80.2%) patients underwent a single shock wave
      lithotripsy session, 18 (18.7%) underwent 2 sessions and 1 (1.1%) patient
      underwent 3 sessions. The overall stone-free rate was 86.5% (83 patients).
      Complications occurred in 10 (10.4%) patients. Shock wave lithotripsy failed in
      13 (13.5%) patients who were successfully treated with ureteroscopy. CONCLUSIONS:
      Our data show that shock wave lithotripsy for large ureteral stones along the
      entire ureter with the unmodified HM3 lithotriptor has a high success rate with
      minimal morbidity. We recommend it as first line treatment.

PMID- 16952658
TI  - Preoperative nomograms for predicting stone-free rate after extracorporeal shock
      wave lithotripsy.
AB  - PURPOSE: Extracorporeal shock wave lithotripsy is currently accepted as a first
      line treatment modality for urolithiasis. In obtaining informed consent it is
      important to inform patients of the stone-free rate with extracorporeal shock
      wave lithotripsy before surgery. The present study was performed to develop
      preoperative nomograms for predicting stone-free rates after extracorporeal shock
      wave lithotripsy. MATERIALS AND METHODS: A total of 435 patients with 507 urinary
      stones were treated with extracorporeal shock wave lithotripsy with a Dornier
      Lithotripter D. Patient age, sex, body mass index, number of stone(s) in each
      treatment, stone length, side and location were evaluated before extracorporeal
      shock wave lithotripsy, and treatment efficacies were evaluated at 3 months after
      each session. The treated stones were divided into 2 groups, those in cases that
      were stone-free with a single extracorporeal shock wave lithotripsy session and
      those in all other cases. Multivariate analysis was performed using a logistic
      regression model. The nomograms were developed by repeating the analysis on 200
      bootstrap samples. RESULTS: Stone length, location and number were identified as
      significant variables on multivariate analysis, and a logistic regression model
      was developed using these variables. The nomograms predicting stone-free rate at
      3 months after single extracorporeal shock wave lithotripsy treatment were
      finally developed from 200 bootstrap samples. In these nomograms the stone-free
      probability was highest for solitary proximal ureteral stones less than 5 mm in
      size (93.8%) and lowest for multiple caliceal stones greater than 21 mm (10.5%).
      CONCLUSIONS: This study demonstrated that stone size, location and number are
      significant predictors of extracorporeal shock wave lithotripsy outcome. We have
      developed nomograms for predicting the stone-free rate of extracorporeal shock
      wave lithotripsy, which is useful for counseling patients with urolithiasis
      before surgery.

PMID- 16952660
TI  - Characterization and management of postoperative hemorrhage following upper
      retroperitoneal laparoscopic surgery.
AB  - PURPOSE: Surgical paradigms may change in the era of laparoscopic surgery. We
      evaluated a conservative nonsurgical approach to postoperative hemorrhage
      following laparoscopic upper retroperitoneal surgery as opposed to the more
      traditional strategy of reexploring the surgical site. MATERIALS AND METHODS: In
      911 laparoscopic procedures performed in 8 years we retrospectively identified
      risk factors and characterized treatment for postoperative hemorrhage. RESULTS:
      We considered postoperative hemorrhage to be present when postoperative
      transfusion was required that could not be accounted for by operative blood loss
      or another definable cause outside of the surgical field. Red blood cell
      transfusion was required after 53 procedures (5.8%), of which 34 (3.7%) were done
      for postoperative hemorrhage. Postoperative hemorrhage occurred only after
      nephrectomy in 3.3% of cases, after partial nephrectomy in 9.9% and after
      adrenalectomy in 5.4%. Multivariate analysis revealed a significant association
      of postoperative hemorrhage with patient age and American Society of
      Anesthesiologists score (preoperative factors), operative time and splenic injury
      (intraoperative factors), and gastrointestinal complications and prolonged
      hospitalization (postoperative factors). Postoperative hemorrhage increased mean
      hospitalization from 2.5 to 6.4 days. No significant differences in post-hospital
      recovery were associated with postoperative hemorrhage. Only 4 of the 34 patients
      (12%) required surgical management of postoperative hemorrhage. All other cases
      were conservatively managed. Outcome after surgical and conservative management
      did not differ except postoperative renal complications tended to be more common
      in the former cases (50% vs 7%). CONCLUSIONS: Most patients with hemorrhage
      following laparoscopic upper retroperitoneal surgery can be treated with
      conservative nonsurgical interventions.

PMID- 16952661
TI  - Chylous ascites after post-chemotherapy retroperitoneal lymph node dissection:
      review of the M. D. Anderson experience.
AB  - PURPOSE: We determined the clinical presentation, risk factors and optimal
      treatment of chylous ascites that develop after retroperitoneal lymph node
      dissection in patients with testicular cancer. MATERIALS AND METHODS: We
      retrospectively reviewed the records of 329 patients who underwent post
      chemotherapy retroperitoneal lymph node dissection at our institution, of whom 23
      (7%) had chylous ascites postoperatively. Clinical and pathological parameters
      were entered into a database. RESULTS: Mean patient age at chylous ascites
      presentation was 32.1 years. On univariate and multivariate logistic regression
      analyses increasing amounts of preoperative chemotherapy (OR 1.24) and
      intraoperative blood loss (OR 1.33) were predictive of chylous ascites. The
      clinical presentation of chylous ascites consisted of abdominal fullness and
      distention in all patients. Initial treatment was paracentesis alone or combined
      with total parenteral nutrition in 77% of patients. An abdominal drain was used
      for persistent ascites in 10 patients. In patients treated conservatively the
      rate of resolution of chylous ascites was 77%. Only 23% of patients required
      peritoneovenous shunt placement. However, shunt use was associated with an 80%
      surgical revision rate. CONCLUSIONS: Conservative treatment resolves most cases
      of postoperative chylous ascites. An abdominal catheter drain should be
      considered for significant or recurring chylous ascites. When a peritoneovenous
      shunt is required, it may be needed for an extensive period for resolution and
      there are significant complications associated with its use. Increasing amounts
      of preoperative chemotherapy and operative blood loss raise the likelihood of
      chylous ascites.

PMID- 16952662
TI  - Neobladder emptying failure in males: incidence, etiology and therapeutic
      options.
AB  - PURPOSE: Neobladder reconstruction is considered the best option for patients
      requiring cystectomy. Limited information is available about incidence, etiology
      and therapeutic options for neobladder emptying failure in males. MATERIALS AND
      METHODS: In a retrospective study we analyzed the data of a consecutive series of
      655 male patients (age range 23 to 82 years, median 63; followup range 0 to 208
      months, median 36.5) who received an ileal neobladder following radical
      cystectomy at our institution. All patients had a complete followup until death
      or until December 2003. Data on all diagnostic and therapeutic procedures
      performed for neobladder emptying failure were collected. RESULTS: Of 655
      patients 75 (11.5%) had at least 1 episode of failure emptying the neobladder
      requiring some form of therapy during followup. Failure was due to dysfunctional
      voiding in 23 patients (3.5%) and mechanical obstruction in 52 patients (8%).
      Causes of mechanical obstruction were benign strictures of the neovesicourethral
      anastomosis (23 patients, 3.5%) or the anterior urethra (11 patients, 1.7%),
      neoplastic obstruction by local tumor recurrence (13 patients, 2.0%) or a
      nonurological malignancy (1 patient, 0.2%), and obstruction by mucosal valves (3
      patients, 0.5%) or a foreign body (1 patient, 0.2%). In 38 of 52 patients with
      mechanical obstruction of the neobladder outlet emptying was fully restored with
      endourological procedures, while in 14 of 52 patients long-term catheterization
      was necessary. Catheterization was the therapy of choice for all patients with
      dysfunctional voiding. CONCLUSIONS: Neobladder emptying failure is of major
      concern but is not an argument against orthotopic diversion. The overall rate of
      transient or permanent neobladder emptying failure in males is high but most of
      the mechanical causes can be managed endoscopically, while the rate of patients
      with long-term catheterization for dysfunctional voiding is relatively low.

PMID- 16952664
TI  - Dorsal buccal mucosa graft urethroplasty for female urethral strictures.
AB  - PURPOSE: We describe the feasibility and complications of dorsal buccal mucosa
      graft urethroplasty in female patients with urethral stenosis. MATERIALS AND
      METHODS: From April 2005 to July 2005, 3 women 45 to 65 years old (average age
      53.7) with urethral stricture disease underwent urethral reconstruction using a
      dorsal buccal mucosa graft. Stricture etiology was unknown in 1 patient, ischemic
      in 1 and iatrogenic in 1. Buccal mucosa graft length was 5 to 6 cm and width was
      2 to 3 cm. The urethra was freed dorsally until the bladder neck and then opened
      on the roof. The buccal mucosa patch was sutured to the margins of the opened
      urethra and the new roof of the augmented urethra was quilted to the clitoris
      corpora. RESULTS: In all cases voiding urethrogram after catheter removal showed
      a good urethral shape with absent urinary leakage. No urinary incontinence was
      evident postoperatively. On urodynamic investigation all patients showed an
      unobstructed Blaivas-Groutz nomogram. Two patients complained about irritative
      voiding symptoms at catheter removal, which subsided completely and spontaneously
      after a week. CONCLUSIONS: The dorsal approach with buccal mucosa graft allowed
      us to reconstruct an adequate urethra in females, decreasing the risks of
      incontinence and fistula.

PMID- 16952665
TI  - 99mTechnetium-mercaptoacetyltriglycine scintigraphy with full bladder in patients
      with severe bladder dysfunction.
AB  - PURPOSE: We evaluated 99mtechnetium-mercaptoacetyltriglycine scintigraphy for
      detecting threshold bladder volume at which upper tract obstruction occurs in
      patients with bladder dysfunction. MATERIALS AND METHODS: A total of 24 patients
      19 to 74 years old with severe bladder dysfunction who underwent 99mtechnetium
      mercaptoacetyltriglycine scintigraphy and videocystometrogram in a 4-year period
      were selected for retrospective study. 99mTechnetium-mercaptoacetyltriglycine
      scintigraphy was done with a full bladder with a mean instilled volume of more
      than 850 ml saline. In patients in whom an obstructed renal outflow pattern was
      observed saline was drained at a rate of 100 ml every 5 minutes while dynamic
      imaging was performed. If results were abnormal, the study was repeated with an
      empty bladder. Differential function, parenchymal transit time index and outflow
      efficiency were calculated. RESULTS: Of the 24 patients 15 had an obstructed
      outflow pattern with a full bladder, which was relieved at a bladder volume of
      less than 390 ml (median 300, range 250 to 600). Only 2 of these 15 patients had
      a normal vesical end filling pressure of less than 20 cm H2O. There was no
      obstruction in 9 patients, of whom 5 had increased vesical end filling pressures.
      Followup in patients who had normal tracer outflow on a full bladder showed no
      decrease in renal function, while a small decrease was seen in patients who had
      obstructed outflow on a full bladder. CONCLUSION: This novel, full bladder
      99mtechnetium-mercaptoacetyltriglycine scintigraphic technique provides the
      ability to detect bladder volumes at which obstructive outflow patterns develop
      in patients with severe bladder dysfunction.

PMID- 16952666
TI  - The effect of terazosin on functional bladder outlet obstruction in women: a
      pilot study.
AB  - PURPOSE: We assessed the effect of terazosin (Hytrin(R)) on functional bladder
      outlet obstruction in women. MATERIALS AND METHODS: Functional bladder outlet
      obstruction was defined as a maximum flow rate of less than 12 ml per second
      combined with a detrusor pressure at maximum flow rate of more than 20 cm H2O in
      pressure flow studies in the absence of neurological disorders or mechanical
      causes. In a prospective pilot study 15 women with functional bladder outlet
      obstruction were treated with terazosin. Terazosin was initiated at 1 mg daily
      and gradually increased to the maintenance dose of 5 mg daily during 2 weeks.
      Symptoms and urodynamic parameters were assessed before and 3 to 4 weeks after
      the initiation of alpha-blocker therapy. RESULTS: While on terazosin, voiding
      symptoms subjectively improved greater than 50% in 10 of the 15 women (p =
      0.002). Median maximum urethral closure pressure at rest decreased significantly
      from 98 to 70 cm H2O (p = 0.001), median maximum detrusor pressure decreased from
      45 to 35 cm H2O (p = 0.008), median detrusor pressure at maximum flow decreased
      from 34 to 27 ml per second and median post-void residual urine decreased from
      120 to 40 ml (p = 0.006 and 0.002, respectively). There was a significant
      increase in the median maximum flow rate from 9 to 20 ml per second and in median
      voided volume from 300 to 340 ml (p = 0.0005 and 0.021, respectively). Storage
      symptoms, functional urethral length and maximum cystometric capacity did not
      change significantly with alpha-blocker therapy (p > 0.05). Overall terazosin
      resulted in a significant improvement in symptoms and urodynamic parameters in 10
      of the 15 women (67%). CONCLUSIONS: Terazosin had a significant symptomatic and
      urodynamic effect in two-thirds of our patients. These results suggest that
      terazosin may be an effective treatment option in women with voiding dysfunction
      due to functional bladder outlet obstruction.

PMID- 16952667
TI  - Patient related risk factors for recurrent stress urinary incontinence surgery in
      women treated at a tertiary care center.
AB  - PURPOSE: We examined patient related risk factors for recurrent stress urinary
      incontinence in women treated at a tertiary referral center. MATERIALS AND
      METHODS: A case-control study was done in 18 to 75-year-old women with signs and
      symptoms of genuine or mixed stress urinary incontinence and no prior surgical
      treatment who underwent an open anti-incontinence procedure between 1990 and 2002
      at our institution. Cases were defined as patients who underwent more than 1 anti
      incontinence surgery and controls were defined as patients who underwent only 1
      anti-incontinence procedure with followup during that period. Cases and controls
      were matched for surgery type, surgeon and date of surgery within 1 year. A total
      of 47 variables were examined, including patient age, parity, incontinence type,
      urodynamic findings, medical history (peripheral vascular, pulmonary and cardiac
      disease), past and concomitant pelvic surgery, social history (alcohol and
      tobacco use) and body mass index. Univariate conditional logistic regression was
      done first to determine which variables were potential protective or risk
      factors. Multivariate conditional logistic regression analysis was then used to
      determine which factors were statistically significant. RESULTS: The records of
      2,550 women with stress or mixed urinary incontinence who underwent an open
      surgical procedure between 1990 and 2002 were reviewed. A total of 53 cases and
      146 controls were identified. Each case was matched with 1 to 4 controls. Data on
      cases and controls were collected using a standardized form. At a significance
      level of 0.05 the possible risk factors for recurrent stress urinary incontinence
      based on univariate analysis were diabetes mellitus (OR 3.579, p = 0.026), pelvic
      organ prolapse (OR 5.635, p = 0.03) and concomitant rectocele repair (OR 5.353, p
      = 0.04). Smoking was marginally protective (OR 0.497, p = 0.068). After
      multivariate conditional logistic regression analysis diabetes mellitus (adjusted
      OR 3.413, p = 0.045), pelvic organ prolapse (adjusted OR 8.195, p = 0.021) and
      concomitant rectocele repair (adjusted OR 17.079, p = 0.012) remained significant
      risk factors, while smoking remained a protective factor (adjusted OR 0.264, p =
      0.012). Body mass index, age, race, parity and estrogen status were not
      identified as risk factors for recurrent stress urinary incontinence requiring a
      second anti-incontinence procedure. CONCLUSIONS: In a cohort of women with stress
      or mixed urinary incontinence treated at our institution between 1990 and 2002
      women with diabetes mellitus, pelvic organ prolapse or concomitant rectocele
      repair were at increased risk for repeat anti-incontinence surgery, while women
      who smoked were at slightly decreased risk.

PMID- 16952668
TI  - A clinical outcomes and cost analysis comparing photoselective vaporization of
      the prostate to alternative minimally invasive therapies and transurethral
      prostate resection for the treatment of benign prostatic hyperplasia.
AB  - PURPOSE: We critically evaluated the clinical outcomes and cost characteristics
      of alternative procedural treatment options for symptomatic benign prostatic
      hyperplasia. MATERIALS AND METHODS: An outcomes and cost analysis was performed
      for benign prostatic hyperplasia treatments, including photoselective
      vaporization, microwave thermotherapy, transurethral needle ablation,
      interstitial laser coagulation and transurethral resection. Clinical outcomes
      were measured by the percent improvement in American Urological
      Association/International Prostate Symptom Score, the maximum uroflowmetry rate
      and quality of life score. An economic simulation model was constructed to
      estimate the expected cost of benign prostatic hyperplasia procedural therapies
      from a payer perspective. The model included costs of initial treatment, followup
      care, adverse events and re-treatment. Sensitivity and threshold analyses tested
      the impact of changing model inputs on base case results. RESULTS: Ablative
      therapies showed better improvement in symptom score, flow rate and quality of
      life score compared to thermotherapy procedures. Photoselective vaporization
      resulted in the largest beneficial changes in American Urological
      Association/International Prostate Symptom Score, the maximum uroflowmetry rate
      and the quality of life score at all time points evaluated, followed by
      transurethral resection and then interstitial laser coagulation. The estimated
      cost was lower for photoselective vaporization than for any other procedural
      option at any interval studied. Sensitivity analyses indicated that the results
      of baseline analyses were robust to reasonable changes in clinical and economic
      inputs to the model. CONCLUSIONS: Compared to alternative treatment options
      photoselective vaporization of the prostate is a clinically efficacious and cost
      effective treatment for symptomatic benign prostatic hyperplasia.

PMID- 16952669
TI  - Laparoscopic cryoablation of renal angiomyolipoma.
AB  - PURPOSE: Angiomyolipomas are rare benign renal tumors which occasionally require
      intervention. Preservation of renal function is essential when treating renal
      angiomyolipoma in patients with multiple or bilateral lesions. We report on the
      first series of patients with renal angiomyolipoma treated with laparoscopic
      cryoablation. MATERIALS AND METHODS: Seven patients with pathologically confirmed
      renal angiomyolipoma underwent laparoscopic cryoablation. Transperitoneal surgery
      with intraoperative ultrasound was performed, followed by clinical monitoring
      with creatinine and axial imaging. RESULTS: Mean patient age was 44.9 years. Six
      patients were female, and 2 patients had associated tuberous sclerosis and
      multiple bilateral angiomyolipoma. In 1 patient 5 lesions were treated, in
      another 3 lesions were treated and in the remaining patients solitary lesions
      were treated. The average size of the largest lesion in each patient was 4.2 cm
      (range 2.5 to 7.0). The procedures were tolerated well with 3 minor complications
      in 2 patients. Average operative time was 170 minutes (range 137 to 232) and
      decreased as expertise was gained. Average estimated blood loss was 116 cc (range
      15 to 250). Renal function was preserved, with mean preoperative and
      postoperative creatinine 0.83 (range 0.6 to 1.6) and 0.91 (range 0.7 to 1.8),
      respectively. Average decrease in estimated creatinine clearance was 8.6 ml per
      minute. Followup imaging using computerized tomography or magnetic resonance
      imaging showed reduction in lesion size, lack of blood flow and no subsequent
      regrowth in all patients. CONCLUSIONS: Laparoscopic cryoablation is a safe and
      feasible minimally invasive, nephron sparing alternative for the treatment of
      angiomyolipoma.

PMID- 16952671
TI  - Central obesity is an independent predictor of erectile dysfunction in older men.
AB  - PURPOSE: There is a growing body of evidence in the literature correlating
      erectile dysfunction to obesity. We investigated the correlation of different
      anthropometric indexes of central obesity to erectile dysfunction. MATERIALS AND
      METHODS: A cross-sectional study was performed including 256 consecutive men 40
      years old or older. All men completed the International Index of Erectile
      Function, and were evaluated routinely with a clinical history, physical
      examination and blood analysis for fasting serum glucose, lipid profile and serum
      testosterone. Anthropometric measures included body mass index, waist
      circumference, sagittal abdominal diameter, maximal abdominal circumference, and
      waist-hip, waist-thigh, waist-height, sagittal abdominal diameter-thigh and
      sagittal abdominal diameter-height indexes. RESULTS: In men 40 to 60 years old
      the different anthropometric indexes of central obesity were not correlated with
      the presence of erectile dysfunction (p > 0.05). Men older than 60 years (41%,
      range 61 to 81) demonstrated an association among erectile dysfunction and waist
      hip index (p = 0.04), waist-thigh index (p = 0.02), sagittal abdominal diameter
      (p = 0.03), sagittal abdominal diameter-height index (p = 0.02) and maximal
      abdominal circumference (p = 0.04). After logistic regression analysis an
      independent effect on the presence of erectile dysfunction was observed for waist
      hip index (OR 8.56, 95% CI 1.44-50.73), sagittal abdominal diameter (OR 7.87, 95%
      CI 1.24-49.75), sagittal abdominal diameter-height index (OR 14.21, 95% CI 1.11
      182.32), maximum abdominal circumference (OR 11.72, 95% CI 1.73-79.18) and waist
      circumference (OR 19.37, 95% CI 1.15-326.55). CONCLUSIONS: This study suggests
      that central obesity, assessed by several anthropometric indicators, is
      associated to the presence of erectile dysfunction in men older than 60 years.
      Sagittal abdominal diameter, sagittal abdominal diameter-height index, maximum
      abdominal circumference, waist circumference and waist-hip index were useful
      indicators to predict the presence of erectile dysfunction.

PMID- 16952672
TI  - The age related decrease in testosterone is significantly exacerbated in obese
      men with the metabolic syndrome. What are the implications for the relatively
      high incidence of erectile dysfunction observed in these men?
AB  - PURPOSE: We examined pooled baseline data from 2 lipid treatment studies to
      evaluate the relationship among total serum testosterone levels, obesity and the
      metabolic syndrome in aging men. MATERIALS AND METHODS: Baseline total serum
      testosterone, lipid, glycemic and anthropometric data were obtained from 864 men
      (mean age 52 years) participating in 2 lipid treatment studies. Inclusion
      criteria for the 2 studies included low-density lipoprotein cholesterol 130 to
      160 mg/dl and triglycerides 350 mg/dl or less. RESULTS: For all patients as well
      as the nonmetabolic syndrome and the metabolic syndrome cohorts, testosterone
      decreased with increasing body mass index (p < 0.0001 for Pearson correlation
      coefficient in all 3 cohorts). Mean baseline total serum testosterone levels in
      obese and severely obese aging men with the metabolic syndrome were around 150
      and 300 ng/dl, respectively, less than that in aging, lean men with no metabolic
      syndrome. The relative contributions of each of the individual National
      Cholesterol Education Program Adult Treatment Panel III components of the
      metabolic syndrome to low serum testosterone in aging men was examined using
      multiple linear regression modeling. Based on these analyses the presence of
      diabetes or fasting serum glucose greater than 110 mg/dl, body mass index 30 kg/m
      or greater, and triglycerides 150 mg/dl or greater each appeared to have a
      clinically relevant association with low serum testosterone. CONCLUSIONS: This
      study demonstrated that aging men with obesity and the metabolic syndrome have a
      significant decrease in total serum testosterone levels compared to aging,
      metabolically healthy men. These data suggest that the well established
      association between erectile dysfunction and pre-diabetes/diabetes (particularly
      in obese pre-diabetic/diabetic patients) may involve a hormonal component.

PMID- 16952675
TI  - Effects of acute treatment with tamsulosin versus alfuzosin on ejaculatory
      function in normal volunteers.
AB  - PURPOSE: The frequency of ejaculatory dysfunction in men varies among the alpha
      blockers used in the treatment of lower urinary tract symptoms associated with
      benign prostatic hyperplasia. We assessed the effect of acute administration of
      tamsulosin, alfuzosin and placebo on ejaculate volume and sperm concentration in
      post-ejaculate urine, and addressed the mechanism of action of tamsulosin and
      alfuzosin on ejaculation. MATERIALS AND METHODS: Using a randomized, 3-way
      crossover design, the effects of 5 days of treatment with 0.8 mg tamsulosin
      daily, 10 mg alfuzosin daily and placebo on ejaculation in healthy adult men were
      compared. The primary end points of the study were ejaculate volume and sperm
      concentration in post-ejaculate urine on each treatment. To aid in clinical
      interpretation of primary efficacy end points, each primary end point was
      transformed into a binary outcome, that is subjects with a greater than 20%
      decrease in ejaculate volume and subjects with a greater than 20% increase in
      sperm concentration in post-ejaculate urine. RESULTS: In healthy volunteers who
      completed the study (48), tamsulosin resulted in significantly decreased
      ejaculate volume (-2.4 +/- 0.17 ml) compared to alfuzosin (+0.3 +/- 0.18 ml, p <
      0.0001 vs tamsulosin) or placebo (+0.4 +/- 0.18 ml, p < 0.0001 vs tamsulosin, p =
      nonsignificant vs alfuzosin). Among completers the incidence of more than 20%
      decreased ejaculate volume was significantly greater with tamsulosin (89.6%)
      compared to alfuzosin (20.8%, p < 0.0001 vs tamsulosin) or placebo (12.5%, p <
      0.0001 vs tamsulosin, p = nonsignificant vs alfuzosin). While on tamsulosin 35.4%
      of 48 completers had complete lack of ejaculation (anejaculation) and no subjects
      experienced anejaculation while on alfuzosin or placebo. CONCLUSIONS: On 0.8 mg
      tamsulosin daily ejaculatory function in subjects was marked by decreased
      ejaculate volume in almost 90% of subjects and anejaculation in approximately 35%
      of participants. These ejaculatory disorders with tamsulosin were not attributed
      to retrograde ejaculation. In contrast, anejaculation was not observed in any
      subjects in the alfuzosin or placebo groups.

PMID- 16952676
TI  - Sexual dysfunction in men with chronic prostatitis/chronic pelvic pain syndrome:
      improvement after trigger point release and paradoxical relaxation training.
AB  - PURPOSE: The impact of chronic pelvic pain syndrome on sexual function in men is
      underestimated. We quantified sexual dysfunction (ejaculatory pain, decreased
      libido, erectile dysfunction and ejaculatory difficulties) in men with chronic
      pelvic pain syndrome and assessed the effects of pelvic muscle trigger point
      release concomitant with paradoxical relaxation training. MATERIALS AND METHODS:
      We treated 146 men with a mean age of 42 years who had had refractory chronic
      pelvic pain syndrome for at least 1 month with trigger point release/paradoxical
      relaxation training to release trigger points in the pelvic floor musculature.
      The Pelvic Pain Symptom Survey and National Institutes of Health-Chronic
      Prostatitis Symptom Index were used to document the severity/frequency of pain,
      urinary and sexual symptoms. A global response assessment was done to record
      patient perceptions of overall therapeutic effects at an average 5-month
      followup. RESULTS: At baseline 133 men (92%) had sexual dysfunction, including
      ejaculatory pain in 56%, decreased libido in 66%, and erectile and ejaculatory
      dysfunction in 31%. After trigger point release/paradoxical relaxation training
      specific Pelvic Pain Symptom Survey sexual symptoms improved an average of 77% to
      87% in responders, that is greater than 50% improvement. Overall a global
      response assessment of markedly or moderately improved, indicating clinical
      success, was reported by 70% of patients who had a significant decrease of 9
      (35%) and 7 points (26%) on the National Institutes of Health-Chronic Prostatitis
      Symptom Index (p < 0.001). Pelvic Pain Symptom Survey sexual scores improved 43%
      with a markedly improved global response assessment (p < 0.001) but only 10% with
      moderate improvement (p = 0.96). CONCLUSIONS: Sexual dysfunction is common in men
      with refractory chronic pelvic pain syndrome but it is unexpected in the mid
      fifth decade of life. Application of the trigger point release/paradoxical
      relaxation training protocol was associated with significant improvement in
      pelvic pain, urinary symptoms, libido, ejaculatory pain, and erectile and
      ejaculatory dysfunction.

PMID- 16952678
TI  - Specific fracture configurations predict sexual and excretory dysfunction in men
      and women 1 year after pelvic fracture.
AB  - PURPOSE: We determined the prevalence and predictors of sexual and excretory
      dysfunction in patients 1 year after pelvic fracture. MATERIALS AND METHODS: The
      multicenter Pennsylvania Trauma Outcomes Study enrolled 1,238 patients and
      contacted them 1 year after injury. Sexual limitations and excretory dysfunction
      (bladder/bowel incontinence) were defined based on responses from the Functional
      Capacity Index. Health related quality of life was determined using SF-36. The
      relationship between specific fracture patterns and dysfunction along with the
      effect of dysfunction on quality of life in patients with pelvic fracture were
      evaluated by multivariate analysis. RESULTS: Of 1,160 eligible patients 292 (26%)
      had pelvic fractures. Sexual dysfunction was reported in 21% vs 14% of those with
      vs without pelvic fractures and bowel or bladder incontinence was reported in 8%
      vs 4%. On multivariate analysis men with sacroiliac fractures were at higher risk
      for sexual (RR 4.0, 95% CI 2.3 to 6.8) and excretory (RR 4.3, 95% CI 1.4 to 13.5)
      dysfunction. In women symphyseal diastasis was associated with sexual (RR 4.8,
      95% CI 2.0 to 11.2) and excretory (RR 12.5, 95% CI 1.9 to 80.2) dysfunction. Of
      patients with pelvic fractures men with sexual dysfunction and women with
      excretory dysfunction had significantly worse quality of life than those without
      dysfunction. CONCLUSIONS: One year after trauma men with sacroiliac fractures and
      women with symphyseal diastasis were at increased risk for sexual and excretory
      dysfunction independent of overt pelvic organ injury. In patients with pelvic
      fracture male sexual dysfunction and female excretory dysfunction were associated
      with decreased quality of life. Our data highlight the need for further study of
      dysfunction following pelvic trauma and interventions to decrease the risk of
      long-term disability.

PMID- 16952680
TI  - Laparoscopic decision making: impact of preoperative reading and laparoscopic
      experience.
AB  - PURPOSE: A competent laparoscopic surgeon requires good technical skills and good
      surgical judgment. The assessment of technical skills using bench models and
      simulators has been well studied. However, there has been a paucity of studies
      examining the cognitive aspects of surgery. We developed a novel tool to assess
      the procedural knowledge and higher level decision making required for successful
      laparoscopic nephrectomy. We assessed the effect of laparoscopic experience and
      the effect of self-preparation or preoperative reading on surgical decision
      making abilities using a novel assessment tool and methodology. MATERIALS AND
      METHODS: A total of 17 novice and advanced urology residents were randomized to
      preoperative reading or no preoperative reading. Subjects viewed laparoscopic
      nephrectomy clips and verbalized their thought processes. Their performance was
      transcribed and blindly rated using a new surgical decision making rating scale.
      RESULTS: The correlation with overall surgical decision making rating scale score
      was good for years of training and moderate for the number of laparoscopic cases
      performed (r = 0.7 and 0.54, respectively, p < 0.05). Preoperative reading did
      not have a significant impact on the overall surgical decision making rating
      scale score (p > 0.05). However, when stratified by laparoscopic experience level
      (fewer than 10 cases), preoperative reading had a significant impact on the
      performance of novices with respect to the knowledge components of the procedure
      but not the judgment domain (each p > 0.05). CONCLUSIONS: Overall preoperative
      reading did not improve the surgical decision making rating scale. Novice
      procedural knowledge benefited from preoperative reading but not surgical
      judgment. The surgical decision making rating scale appears promising and it may
      have future implications for assessing surgical competency.

PMID- 16952681
TI  - Bringing prostate cancer quality of life research back to the bedside:
      translating numbers into a format that patients can understand.
AB  - PURPOSE: Although measuring quality of life of patients with prostate cancer
      serves important research goals, its primary clinical purpose is informing
      patients. Sophisticated quality of life measures produce purely numerical results
      that patients have difficulty understanding. We present an approach that
      preserves the methodological strengths of validated multi-item measures but
      provides more accessible information for clinical use. MATERIALS AND METHODS:
      Using validated indexes measuring urinary, bowel and sexual function we surveyed
      patients with clinically localized prostate cancer before treatment and at
      intervals thereafter. Based on patient responses to parallel distress measures we
      defined 3 levels of function, including normal-no abnormal symptom, intermediate
      any abnormal symptom but none severely abnormal and poor-any severely abnormal
      symptom. We then translated patient survey results into these levels. To assess
      measurement properties we compared average symptom distress scores in patients at
      each symptom level. RESULTS: Levels of function and patient distress scores
      correlated strongly. Large and approximately equal differences in distress scores
      separated patients at successive levels in all symptom indexes (effect size
      greater than 1.2, p < 0.0001). Using these categories we created tables showing
      24-month outcomes in 417 previously reported patients by pretreatment symptom
      level and treatment, providing a tool for patients to determine posttreatment
      outcomes in similar patients. CONCLUSIONS: Using symptom indexes to define levels
      of function produces a quality of life metric that is valid, defines quantitative
      intervals, is transparent and may be more useful to patients. This approach
      provides methodologically sound outcome information to patients attempting to
      choose a prostate cancer treatment.

PMID- 16952683
TI  - Retrograde proximal rigid ureteroscopy and pyeloscopy in prepubertal children:
      safe and effective.
AB  - PURPOSE: Traditionally, rigid ureteroscopy in adults has been reserved for distal
      ureteral procedures, due to the risk of injury associated with proximal
      ureteroscopy. However, the safety of proximal rigid ureteroscopy in prepubertal
      children is not well established. MATERIALS AND METHODS: We retrospectively
      evaluated all prepubertal children (12 years old and younger) who underwent
      attempted rigid proximal ureteroscopy and pyeloscopy. The indications for
      ureteroscopy were treatment of ureteral and/or renal pelvic calculi, and
      evaluation of hematuria. All patients were evaluated postoperatively with renal
      and bladder ultrasonography and abdominal radiography (if stone was visible
      before treatment). RESULTS: A total of 24 consecutive children 3.4 to 12 years
      old underwent 24 ureteropyeloscopic procedures. Of these children 20 (83%)
      successfully underwent 20 rigid ureteroscopic and pyeloscopic procedures.
      However, 4 procedures (17%) were converted from rigid to flexible endoscopy to
      perform 4 successful ureteropyeloscopies. The indications for ureteroscopy were
      treatment of ureteral and/or renal pelvic calculi in 22 patients and evaluation
      of hematuria in 2. Followup was 0.6 to 3.6 years (mean 1.9) for the patients
      undergoing rigid ureteropyeloscopy. All children with calculi were rendered stone
      free based on direct visualization by complete ureteroscopy and pyeloscopy of the
      affected system. No complications occurred during any of the procedures.
      CONCLUSIONS: Proximal rigid ureteroscopy and pyeloscopy can be safely applied
      toward treatment of proximal ureteral and renal pelvic calculi as well as
      diagnostic ureteropyeloscopy in prepubertal children. The technique has several
      advantages compared to flexible ureteroscopy.

PMID- 16952684
TI  - Is bowel preparation required before cystoplasty in children?
AB  - PURPOSE: We evaluated whether bowel preparation is required before augmentation
      cystoplasty in children. MATERIALS AND METHODS: A total of 46 consecutive
      children underwent cystoplasty using detubularized ileum between 1998 and 2004.
      Group 1 (24 patients) underwent standard mechanical bowel preparation with sodium
      picosulfate, a bowel enema (sodium phosphate) if required and clear fluids for 24
      hours preoperatively. Group 2 (22 patients) received no bowel preparation and was
      on a normal diet preoperatively. One dose of parenteral triple antibiotics was
      administered at induction of anesthesia in both groups. The surgical technique
      was similar in both groups. Postoperatively, group 1 had a nasogastric tube in
      situ, while group 2 had no nasogastric tube. The main outcome measures were
      hospital stay (days), time to commencing fluids postoperatively (hours),
      incidence of urinary tract infection during hospitalization and incidence of
      wound infection. RESULTS: Median postoperative stay was 5 days (range 4 to 7) in
      group 1 and 4 days (3 to 6) in group 2. Median time to intake of oral fluids was
      48 hours (range 24 to 72) in group 1 and 24 hours (12 to 48) in group 2. Three
      patients in group 1 and 2 in group 2 had a symptomatic urinary tract infection
      during the postoperative course. One patient in each group had a superficial
      wound infection. CONCLUSIONS: There were no significant differences in hospital
      stay or postoperative complications between the 2 groups. This series suggests
      that bowel preparation is unnecessary for children undergoing cystoplasty.

PMID- 16952688
TI  - Tunneled tunica vaginalis flap is an effective technique for recurrent
      urethrocutaneous fistulas following tubularized incised plate urethroplasty.
AB  - PURPOSE: In the last several years the use of the tubularized incised plate
      hypospadias repair has greatly increased. The most significant complication after
      this mode of urethroplasty is urethrocutaneous fistula development. Tunneled
      tunica vaginalis flap is a well described technique for repair of
      urethrocutaneous fistula. However, to our knowledge its use after tubularized
      incised plate repair has not yet been described. We present our results with this
      technique. MATERIALS AND METHODS: We retrospectively reviewed all patients
      undergoing repair of urethrocutaneous fistula after initial tubularized incised
      plate repair between January 2001 and December 2005. We analyzed the initial
      number and location of fistulas, number of previous urethrocutaneous fistula
      repairs, duration of surgery, and intraoperative and postoperative complications.
      RESULTS: A total of 16 boys (median age 2.2 years) underwent tunica vaginalis
      flap repair at our institution for urethrocutaneous fistula following initial
      failed tubularized incised plate repair. Of these patients 4 had not previously
      undergone urethrocutaneous fistula repair and 12 had undergone 1 to 4 failed
      repair attempts. All boys had a subcoronal fistula and 8 had additional fistulas
      along the penile shaft, 4 each with 3 and 4 fistulas, including 1 penoscrotal
      fistula. Mean surgical time was 45 minutes, and no intraoperative or
      postoperative complications occurred. After a mean followup of 18 months (range 4
      to 36) no patient had recurrence of urethrocutaneous fistula. CONCLUSIONS:
      Tunneled tunica vaginalis flap repair is a highly successful technique for the
      treatment of urethrocutaneous fistula after initial failed tubularized incised
      plate repair. The technique is technically simple to perform, and we encountered
      no complications. Tunneled tunica vaginalis flap repair should be considered for
      treating urethrocutaneous fistula following initial failed tubularized incised
      plate hypospadias surgery, particularly in a repeat surgical setting.

PMID- 16952692
TI  - Redo ureteroneocystostomy using an extravesical approach in pediatric renal
      transplant patients with reflux: a retrospective analysis and description of
      technique.
AB  - PURPOSE: Vesicoureteral reflux and pyelonephritis following transplantation may
      significantly contribute to renal damage and premature graft loss. We report our
      retrospective experience with redo ureteral reimplantation of refluxing pediatric
      renal transplants and describe our surgical technique. MATERIALS AND METHODS: We
      identified 20 children with a diagnosis of symptomatic post-transplant
      vesicoureteral reflux, of whom 16 underwent redo ureteral reimplantation. Patient
      characteristics including etiology of end stage renal disease, presenting
      symptoms, serum creatinine and postoperative followup were documented. The
      presence or absence of lower urinary tract dysfunction was documented and values
      between the 2 groups were analyzed for significance. RESULTS: All 20 patients
      presented after assessment for a febrile urinary tract infection, and 35% had
      concurrent lower urinary tract dysfunction. Median interval between
      transplantation and vesicoureteral reflux diagnosis was 1.3 years, and mean
      vesicoureteral reflux grade was 3.2. Patients with lower urinary tract
      dysfunction presented significantly earlier and had a higher postoperative serum
      creatinine than those without lower urinary tract dysfunction (1.1 vs 1.7 years,
      p = 0.048). Redo reimplantation was performed in 94% of patients using an
      extravesical approach with ureteral stent placement. Seven of 16 patients
      underwent followup voiding cystourethrogram, with 5 demonstrating resolution and
      2, both with lower urinary tract dysfunction, exhibiting persistent
      vesicoureteral reflux. At a mean followup of 3.6 years 25% of patients
      experienced recurrent pyelonephritis, while 75% were asymptomatic. One instance
      of anastomotic stricture occurred in a patient with lower urinary tract
      dysfunction. CONCLUSIONS: Effective repair of post-transplantation vesicoureteral
      reflux can be performed using an extravesical technique, facilitated by
      preoperative ureteral stent placement. Patients with lower urinary tract
      dysfunction are likely to present earlier after transplantation than those
      without lower urinary tract dysfunction, and may have an increased risk of
      persistent vesicoureteral reflux and renal damage despite surgical correction.

PMID- 16952694
TI  - The cost-effectiveness of dextranomer/hyaluronic acid copolymer for the
      management of vesicoureteral reflux. 1: substitution for surgical management.
AB  - PURPOSE: We examined the cost-effectiveness of dextranomer/hyaluronic acid
      copolymer injection in patients who would otherwise undergo ureteral
      reimplantation. MATERIALS AND METHODS: A model for managing vesicoureteral reflux
      has previously been created. We now update the model to compare the costs of
      treating vesicoureteral reflux using standard methods (ie ureteral reimplantation
      after failed medical therapy) with the costs of dextranomer/hyaluronic acid
      injection. RESULTS: In the first scenario created dextranomer/hyaluronic acid
      injection is substituted for ureteral reimplantation when surgical intervention
      would be performed for treatment of breakthrough infection or failure of the
      reflux to resolve. For dextranomer/hyaluronic acid injection to have equal cost
      effectiveness compared to ureteral reimplantation in this scenario success rates
      for dextranomer/hyaluronic acid injection would need to be 57.8% per ureter for
      patients with unilateral reflux and 75.3% per ureter for patients with bilateral
      reflux. However, if increasing grades of reflux require increasing volumes of
      dextranomer/hyaluronic acid, success rates would need to be 72.5% for patients
      with unilateral reflux and 93.8% for patients with bilateral reflux. In the
      second scenario created dextranomer/hyaluronic acid injection is repeated if it
      fails to resolve the reflux after the first injection. Success rates to obtain
      equal cost-effectiveness for the repeat dextranomer/hyaluronic acid injection
      would need to be 0%, 11.4% and 60.3% in patients with unilateral reflux if the
      respective success rates of the initial injection were 85%, 70% and 55%. Success
      rates for the second dextranomer/hyaluronic acid injection would need to be 0%,
      29.1% and 76.7% per ureter in patients with bilateral reflux if the respective
      success rates of the initial injection were 85%, 70% and 55%. If increasing
      volumes of dextranomer/hyaluronic acid were required for increasing grades of
      reflux, a second dextranomer/hyaluronic acid injection would not be a viable
      option. CONCLUSIONS: Based on our results, dextranomer/hyaluronic acid injection
      may be more cost-effective than ureteral reimplantation for children who meet
      standard criteria for surgical therapy, especially for lower grades of reflux. If
      increasing grades of reflux require an increased volume of dextranomer/hyaluronic
      acid, then injection would likely be cost-effective only for grades I and II
      unilateral and bilateral reflux, and perhaps unilateral grade III reflux.

PMID- 16952696
TI  - Postoperative ureteral obstruction after subureteral injection of
      dextranomer/hyaluronic Acid copolymer.
AB  - PURPOSE: Subureteral injection of dextranomer/hyaluronic acid copolymer is widely
      accepted for the treatment of primary vesicoureteral reflux. Few studies document
      the incidence of surgically relevant postoperative obstruction or the
      characteristics of patients at risk. MATERIALS AND METHODS: Four institutions had
      reported surgically relevant postoperative obstruction to representatives of Q
      Med Scandinavia, the manufacturers of Deflux (dextranomer/hyaluronic acid). All
      children undergoing dextranomer/hyaluronic acid injection at these institutions
      were evaluated in this study. Patients requiring postoperative stenting were
      retrospectively reviewed for pertinent history, volume injected, technique of
      injection, duration of symptoms before intervention, duration of intervention and
      final outcome. RESULTS: A total of 745 patients (1,155 ureters) underwent
      injection. Five patients (6 renal units, 7 ureters) required stenting for
      obstructive symptoms and hydronephrosis, of whom 4 immediately became
      symptomatic. All patients had been injected with up to 1 ml
      dextranomer/hyaluronic acid. Four patients (80%) had either a neurogenic bladder
      or dysfunctional voiding. All stents were placed and removed without
      complications, with complete resolution of symptoms in all patients. Length of
      stenting ranged from 2 to 6 weeks. No patient required open surgery. One of 2
      patients undergoing postoperative voiding studies had development of recurrent
      vesicoureteral reflux. CONCLUSIONS: Dextranomer/hyaluronic acid injection is
      associated with a small risk of postoperative ureteral obstruction requiring
      endoscopic intervention, with an overall incidence of less than 0.7% of patients
      injected. Patients with voiding dysfunction or neurogenic bladder may be at
      increased risk. Intervention with temporary ureteral stenting is effective,
      technically simple and curative.

PMID- 16952697
TI  - Reference ranges for cystographic bladder capacity in children-with special
      attention to vesicoureteral reflux.
AB  - PURPOSE: Linear correlations for cystometric/cystographic bladder capacity with
      age universally serve as clinical yardsticks in pediatric urology and nephrology.
      However, these correlations do not account for growth or the range in values, as
      the relation of cystometric/cystographic bladder capacity with age is nonlinear.
      Also, vesicoureteral reflux might influence the size of cystometric/cystographic
      bladder capacity, since small and large bladder capacities have been reported in
      conjunction with reflux. We decided to use the data sets of the International
      Reflux Study in Children to construct full reference ranges for
      cystometric/cystographic bladder capacity and age, for comparison with existing
      reference ranges in normal children, and to study the relation between bladder
      capacity and refluxing volume. MATERIALS AND METHODS: In the International Reflux
      Study in Children 386 patients with grade III or IV vesicoureteral reflux were
      followed with isotope cystography for 10 years. To follow the grade of reflux, x
      ray cystography was also used at 60-month intervals. The 386 children, who were 1
      month to 12 years old, were randomized into 2 groups-those undergoing surgery and
      those receiving medical treatment. For both groups data were available on
      cystometric/cystographic bladder capacity, refluxing volume, reflux grade and
      reflux outcome. RESULTS: The distribution of cystometric/cystographic bladder
      capacity vs age is logarithmic, with a wide range between the 5th and 95th
      percentiles, and a clear nonlinear relation between bladder capacity and age (p <
      0.001). Gender has no influence on cystometric/cystographic bladder capacity. No
      difference in bladder capacity exists between persistence or resolution of
      vesicoureteral reflux (p < 0.78), between grade III and grade IV reflux (p <
      0.94), or between unilateral and bilateral reflux (p < 0.74). Thus, refluxing
      volume correlated only with reflux grade, not with cystometric/cystographic
      bladder capacity or age. CONCLUSIONS: With or without vesicoureteral reflux
      values for cystometric/cystographic bladder capacity range widely in children,
      and correlate logarithmically with age. For clinical decisions the full reference
      range for age, flanked by the 5th and 95th percentiles, should be used to assess
      individual values for cystometric/cystographic bladder capacity, rather than
      linear functions.

PMID- 16952698
TI  - Does surgical release of secondary spinal cord tethering improve the prognosis of
      neurogenic bladder in children with myelomeningocele?
AB  - PURPOSE: The diagnostic criteria for secondary tethering of the spinal cord in
      children with prior closure of an open spinal defect are not well defined.
      Urological, neurological or orthopedic deterioration during followup remains the
      only strong indicator for the diagnosis of this condition. However, the outcome
      of untethering surgery cannot always be predicted. The aim of this study was to
      determine neurourological outcome after secondary untethering surgery in children
      with myelomeningocele. MATERIALS AND METHODS: Of 401 children with
      myelomeningocele followed at our multidisciplinary spina bifida clinic between
      1996 and 2005, 56 (14%) were diagnosed with secondary tethering of the spinal
      cord (median age at diagnosis 4.1 years). The diagnosis was based on urological
      and neuro-orthopedic deterioration in 58% and 42% of children, respectively.
      Preoperative urological findings were compared with 6-month postoperative
      findings. RESULTS: Febrile urinary tract infection, upper tract dilatation and
      vesicoureteral reflux were preoperatively documented in 48.2%, 19% and 30% of the
      56 children, respectively. At 6 months postoperatively urine cultures were
      sterile in 34% of patients and upper tract dilatation completely resolved in 45%.
      For all grades of vesicoureteral reflux complete resolution occurred in 47% of
      patients. Urodynamic parameters in terms of cystometric bladder capacity and
      detrusor leak point pressure substantially improved 6 months after untethering
      surgery (125 vs 170 ml and 69.1 vs 47.5 cm H2O, respectively, p < 0.05).
      Assessment of urodynamic findings in 19 children at 1 year failed to demonstrate
      a significant change in these parameters. A subgroup analysis according to
      patient age at untethering surgery revealed urodynamic improvement was more
      significant in children who were diagnosed and treated before age 7 years.
      CONCLUSIONS: Secondary tethering of the spinal cord is a major risk factor for
      urological and neurological deterioration in children with myelomeningocele.
      Close urological surveillance remains the most valuable tool in the early
      diagnosis. Our study shows that secondary untethering surgery may significantly
      improve urological outcome.

PMID- 16952700
TI  - Natural history of patients with multicystic dysplastic kidney-what followup is
      needed?
AB  - PURPOSE: Most clinicians recommend followup with annual ultrasound for patients
      with multicystic dysplastic kidney. The aim of this study was to determine
      whether followup ultrasound provides any clinical benefit. MATERIALS AND METHODS:
      We retrospectively reviewed the charts of 73 patients who were diagnosed with
      multicystic dysplastic kidney between October 1991 and August 2005. Data were
      analyzed with respect to patient characteristics and followup information.
      RESULTS: We identified 61 patients (43 boys and 18 girls) with adequate followup.
      A total of 49 patients (80%) were diagnosed prenatally and 12 (20%) postnatally.
      Associated urological anomalies were noted in 16 patients (26%). Median followup
      was 2.6 years (range 6 months to 37.5 years). Ultrasound examinations showed
      complete involution in 25 patients (41%) and partial regression in 18 (30%). The
      size of the multicystic dysplastic kidney increased in 1 patient (1.6%) and was
      unchanged in 17 (28%) without any pathological manifestations. Median age at
      complete involution was 2.1 years (range 36 days to 13.7 years). Patients with
      contralateral compensatory hypertrophy had more rapid complete involution.
      Urinary tract infection developed in 6 patients, of whom 1 was ultimately found
      to have reflux and 1 had ureteropelvic junction obstruction. CONCLUSIONS: In our
      patients with unilateral multicystic dysplastic kidney ultrasound provided little
      clinically important information. Our data and a review of the literature suggest
      that once the diagnosis is made, no urological followup is needed. The primary
      care provider should monitor patients with multicystic dysplastic kidney for
      hypertension, abdominal mass and urinary tract infection.

PMID- 16952702
TI  - Benign cystic lesions of the rete testes.

PMID- 16952701
TI  - Failure of shortening and inversion of the perinatal gubernaculum in the
      cryptorchid long-evans orl rat.
AB  - PURPOSE: Failure of testicular descent occurs in about 65% of spontaneously
      cryptorchid Long-Evans orl rats. Development of the fetal gubernaculum is
      dependent on expression of leucine rich G protein coupled receptor (also known as
      G protein coupled receptor affecting testicular descent) and its ligand, insulin
      like 3. We studied testicular descent and mRNA expression of insulin-like 3 and
      leucine rich G protein coupled receptor in Long-Evans orl and Long-Evans wild
      type rats during perinatal development. MATERIALS AND METHODS: Long-Evans orl and
      Long-Evans wild-type males obtained at gestational days 18 to 21 and day of birth
      were preserved in RNAlater for at least 24 hours. The size and position of the
      testes, kidneys and gubernacula were determined by microdissection and image
      analysis. Leucine rich G protein coupled receptor mRNA expression was analyzed in
      fetal gubernacula (gestational days 18 to 21) using real-time reverse
      transcriptase polymerase chain reaction with SYBR Green detection. Insulin-like 3
      mRNA expression in fetal testis (gestational days 18 and 20) was determined by
      semiquantitative reverse transcriptase polymerase chain reaction. RESULTS:
      Testicular position was similar in Long-Evans orl and Long-Evans wild-type fetal
      rats. However, gubernacula were narrow (p < 0.001) and elongated (p < or = 0.01)
      in Long-Evans orl compared to Long-Evans wild-type fetuses at all time points.
      Inversion of both gubernacula occurred by the day of birth in 45% of Long-Evans
      orl and 100% of Long-Evans wild-type males (p < 0.001). Leucine rich G protein
      coupled receptor mRNA expression decreased with age and, similar to insulin-like
      3 mRNA, was not consistently different between strains. CONCLUSIONS: These data
      suggest that the impaired shortening of the Long-Evans orl gubernaculum may
      interfere with the timing and quality of its inversion at birth, leading to
      failure of testicular descent in some newborn males. However, fetal testicular
      descent and the expression of leucine rich G protein coupled receptor and insulin
      like 3 mRNA appear to be normal in this strain.

PMID- 16952703
TI  - Computerized tomography diagnosis of urachal cyst harboring teratoma.

PMID- 16952704
TI  - In vivo assessment of radio frequency induced thermal damage of kidney using
      optical spectroscopy.
AB  - PURPOSE: Radio frequency ablation is a promising modality for treating small
      renal tumors. Several studies have been published showing its efficacy. A major
      drawback in the current management of renal tumors with radio frequency ablation
      is the lack of an effective modality to accurately monitor the progress of the
      ablation zone in real-time fashion. Previous studies have demonstrated the
      feasibility of using optical spectroscopy to assess tissue thermal damage,
      especially in hepatic lesions. We examined the feasibility of this technology in
      the setting of renal radio frequency ablation. MATERIALS AND METHODS: A portable
      spectroscopic system was used to acquire in vivo fluorescence and diffuse
      reflectance spectra from porcine renal tissue undergoing radio frequency ablation
      in real-time fashion with simultaneous temperature recordings. Fluorescence and
      diffuse reflectance spectral data were then correlated with various degrees of
      thermal damage and temperature recordings. RESULTS: The most noticeable change in
      fluorescence characteristics of renal tissue resulting from thermal coagulation
      was a strong decrease in fluorescence intensity between 400 and 550 nm. When
      fully coagulated, a significant increase in diffuse reflectance intensity was
      observed between 500 and 800 nm. CONCLUSIONS: Optical spectroscopy, specifically
      fluorescence and diffuse reflectance spectroscopy, differs significantly in
      porcine renal tissues with varying degrees of thermal damage from radio frequency
      ablation in an in vivo setting. Future clinical studies with sufficient sample
      size are required to validate the potential of these findings. Optical
      diagnostics may prove to be a rapid, noninvasive, low cost option for monitoring
      the tumor response to radio frequency based ablative techniques. It may be
      integrated into future radio frequency ablation probes.

PMID- 16952705
TI  - Increased serum leptin levels and over expression of leptin receptors are
      associated with the invasion and progression of renal cell carcinoma.
AB  - PURPOSE: Leptin, an adipocyte derived cytokine that is closely associated with
      obesity, was recently shown to be involved in carcinogenesis and cancer
      progression. Because obesity is a significant risk factor for renal cell
      carcinoma, we investigated the link between leptin and the development of renal
      cell carcinoma. MATERIALS AND METHODS: Associations between preoperative serum
      leptin levels and leptin receptor expression in tumor specimens and various
      clinicopathological parameters were analyzed in 57 patients with renal cell
      carcinoma. RESULTS: Serum leptin levels were 1.2 to 16.2 ng/ml (mean 4.5). Of 57
      tumors 22 (38.6%) demonstrated high leptin receptor expression. Serum leptin
      levels were significantly higher in patients with vs without tumor specimen
      venous invasion (p = 0.030) and higher in patients with high vs low leptin
      receptor expression (p = 0.019). There were significant associations between high
      leptin receptor expression and the presence of venous invasion (p = 0.013),
      histological type (p = 0.0076) and regional lymph node metastasis (p = 0.047). Of
      42 patients with N0M0 disease those with serum leptin 5.0 ng/ml or more had
      significantly shorter progression-free survival than patients with lower levels
      (p = 0.0043). Multivariate Cox proportional hazards model analysis demonstrated
      that higher serum leptin was an independent predictor of progression-free
      survival (p = 0.0406). CONCLUSIONS: Leptin and leptin receptor could have a key
      role in the invasion of renal cell carcinoma and they could be valuable
      predictors of progression.

PMID- 16952706
TI  - Leptin promotes invasiveness of murine renal cancer cells via extracellular
      signal-regulated kinases and rho dependent pathway.
AB  - PURPOSE: Obesity is a significant risk factor for renal cell carcinoma. The
      adipocyte derived cytokine leptin, which controls body weight homeostasis through
      food intake and energy expenditure, recently provided a potential link between
      obesity and cancer development. We examined whether leptin promotes the
      invasiveness of renal cancer cells and we investigated its underlying signaling
      pathway. MATERIALS AND METHODS: Leptin receptor expression in the 6 human renal
      cancer cell lines Caki-1, ACHN, 769P, A498, SKRC44 and SKRC49, and in the murine
      renal cancer cell line Renca was examined by reverse transcriptase-polymerase
      chain reaction and Western blotting. The effect of leptin on renal cancer cell
      invasiveness was assessed by the invasion of cells through Matrigel coated
      Transwell inserts. Leptin induced intracellular signaling was examined by Western
      blotting. RESULTS: Leptin receptor was detected in all renal cancer cells
      examined at the mRNA and protein levels. Leptin increased Renca cell invasiveness
      at 1 ng/ml (p < 0.05). There was up to 3-fold invasiveness compared to untreated
      cells at 100 ng/ml with the activation of extracellular signal-regulated kinases
      and rho guanosine triphosphatase (p < 0.01). Leptin induced activation of rho
      guanosine triphosphatase was inhibited not only by the rho kinase inhibitor
      Y27632, but also by the MEK1 inhibitor PD98059, of which each inhibited leptin
      induced invasion of Renca cells (p < 0.01). CONCLUSIONS: Leptin promoted the
      invasiveness of murine renal cancer cells via extracellular signal-regulated
      kinases and rho guanosine triphosphatase dependent pathways. Rho guanosine
      triphosphatase was a downstream effector of extracellular signal-regulated
      kinases in leptin induced invasion. Leptin signaling could have a key role in
      renal cell carcinoma invasion.

PMID- 16952707
TI  - Vitamins C and K3 sensitize human urothelial tumors to gemcitabine.
AB  - PURPOSE: We evaluated the antitumor effects of vitamins C and K3 for human
      urothelial carcinoma and the potential use of the combination of vitamins C plus
      K3 as a sensitizing agent for conventional chemotherapy for urothelial carcinoma.
      MATERIALS AND METHODS: The antiproliferative and apoptotic effects of vitamin C
      alone, vitamin K3 alone, vitamins C plus K3, gemcitabine alone and gemcitabine
      plus vitamins C plus K3 were assessed in vitro by MTT (3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide) assay, propidium iodide staining and flow
      cytometry. For in vivo studies we implanted UMUC-14 tumorigenic urothelial
      carcinoma cells into the subcutis of nude mice. One week later we treated 10 mice
      each with saline (control), vitamins C plus K3, gemcitabine or gemcitabine plus
      vitamins C plus K3. Treatment was continued for 4 weeks, followed by necropsy.
      Tumor volume was measured and tumor kinetics were established. Apoptosis and
      proliferation were evaluated in tumor sections using immunohistochemistry and
      TUNEL assay. RESULTS: Vitamins C plus K3 induced cytostasis and caused apoptosis
      to a greater degree than either vitamin alone (p < 0.05). Vitamins C plus K3 also
      substantially augmented the effects of gemcitabine in vitro. There were 32.3%
      apoptosis with gemcitabine plus vitamins C plus K3, 5.3% with gemcitabine alone
      and 15.8% with vitamins C plus K3 alone (p < 0.05). In vivo tumor growth was
      substantially inhibited by gemcitabine plus vitamins C plus K3 compared with that
      in the control or for either agent alone. Mean tumor weight and growth rate in
      the gemcitabine plus vitamins C plus K3 group (237 mg and 11.3 mm3 daily) were
      decreased compared with those in the control (530 mg and 34.3 mm3 daily), and
      those for vitamins C plus K3 alone (490 mg and 25.2 mm3 daily) and gemcitabine
      alone (400 mg and 21.3 mm3 daily) (p < 0.05). CONCLUSIONS: Vitamins C and K3 have
      significant antiproliferative and apoptotic effects when used in combination.
      This combination enhances the efficacy of gemcitabine against bladder cancer in
      vivo.

PMID- 16952708
TI  - The role of serotonin (5-hydroxytryptamine1A and 1B) receptors in prostate cancer
      cell proliferation.
AB  - PURPOSE: Serotonin (5-hydroxytryptamine), a monoamine neurotransmitter released
      by prostate neuroendocrine cells, has a fundamental role in tumor growth,
      differentiation and gene expression. We investigated the effect of 5
      hydroxytryptamine and 5-hydroxytryptamine antagonists on the growth of prostate
      cancer cells and we identified 5-hydroxytryptamine receptor expression in PC3
      cells and in human hormone refractory prostate cancer tissue. MATERIALS AND
      METHODS: A total of 12 preparations of hormone refractory PC3 human prostate
      cancer cells were incubated with 5-hydroxytryptamine, or the 5-hydroxytryptamine
      receptor antagonists 5-hydroxytryptamine1A, 1B, 1D, 2, 3 or 4. After 72 hours
      cell viability was assessed using the crystal violet assay. PC3 cells treated
      with 5-hydroxytryptamine1A and 1B antagonists were investigated for apoptosis
      using flow cytometry. PC3 cells and sections of hormone refractory human prostate
      cancer tissue were studied by immunohistochemistry and Western blot analysis.
      RESULTS: In PC3 cells 5-hydroxytryptamine caused dose dependent proliferation
      with a maximum increase of 15% in 12 preparations at a concentration of 10(-8) M
      at 72 hours compared to controls (p < 0.0001). At a concentration of 10(-4) M at
      72 hours the 5HT1A antagonist NAN-190 hydrobromide and the 5-hydroxytryptamine1B
      antagonist SB224289 HCl (Tocris Laboratories, Bristol, United Kingdom) induced a
      20% and 78% inhibitory effect, respectively, on PC3 cell growth compared to that
      in controls (p < 0.0001). In PC3 cells 5-hydroxytryptamine1A and 1B antagonists
      demonstrated apoptosis after 24 and 48 hours of incubation. Immunostaining for 5
      hydroxytryptamine1A and 1B receptors was seen in PC3 cells and prostate cancer
      tissue. Western blot analysis demonstrated 5-hydroxytryptamine1A and 1B receptor
      proteins with 46 and 43 kDa bands, respectively. CONCLUSIONS: In PC3 prostate
      cancer cells 5-hydroxytryptamine1A and to a greater extent 5-hydroxytryptamine1B
      antagonists significantly inhibit growth and induce apoptosis. To our knowledge
      growth inhibition caused by the 5-hydroxytryptamine1B antagonist SB224289 HCl is
      a novel finding, as is apoptosis caused by the 2 antagonists 5
      hydroxytryptamine1A and 1B. This effect is most likely mediated via 5
      hydroxytryptamine1A and 1B receptors. Therefore, our results imply that 5
      hydroxytryptamine1A and in particular 5-hydroxytryptamine1B receptor antagonists
      warrant further investigations as potential anti-neoplastic agents.

PMID- 16952709
TI  - Contrast enhanced ultrasound for radio frequency ablation of canine prostates:
      initial results.
AB  - PURPOSE: We determined the feasibility of contrast enhanced ultrasound for radio
      frequency ablation of the entire prostate as a method of minimally invasive
      treatment for prostate cancer in a canine model. MATERIALS AND METHODS: Approval
      of the Institutional Animal Use and Care committee was obtained. Initially 5 dogs
      (group 1) were tested using variable power (5 to 30 W), time (4 to 12 minutes),
      bolus (0.01 to 0.04 ml/kg) and infusion (3 to 11 ml per minute at 0.015
      microl/kg) injections of an ultrasound contrast agent with conventional grayscale
      power Doppler and pulse inversion harmonic imaging to establish optimal
      parameters. Subsequently 4 dogs (group 2) underwent entire prostate ablation
      using parameters based on group 1. The size of the thermal lesions and residual
      viable tissue was measured with ImageJ software (National Institutes of Health,
      Bethesda, Maryland) on ultrasound and pathological study. Linear regression and
      Student's t test were used for statistical analysis. RESULTS: A bolus of 0.04
      ml/kg, an infusion of 11 ml per minute at 0.015 microl/kg and the contrast
      enhanced pulse inversion harmonic imaging mode were ranked best for guiding
      ablation. Thermal lesion volume was proportional to ablation power and time.
      There was no significant difference in measured thermal lesion size in group 1
      between ultrasound and pathological findings (mean +/- SD 1.51 +/- 0.74 and 1.46
      +/- 0.74 cm3, p = 0.56) or in residual viable tissue in group 2 (0.43 +/- 0.043
      and 0.41 +/- 0.291 cm3, p = 0.21). The average volume of prostate ablation
      achieved in group 2 was 96.3%. CONCLUSIONS: Contrast enhanced pulse inversion
      harmonic imaging is able to guide, monitor and control radio frequency ablation
      of the entire prostate.

PMID- 16952710
TI  - Prostacyclin production in tryptase and thrombin stimulated human bladder
      endothelial cells: effect of pretreatment with phospholipase A2 and
      cyclooxygenase inhibitors.
AB  - PURPOSE: Thrombin and tryptase stimulation of human bladder microvascular
      endothelial cells (Cambrex Bioscience, Walkersville, Maryland) results in the
      production of multiple membrane phospholipid derived inflammatory mediators via
      the activation of a calcium independent phospholipase A2 that may have important
      implications in bladder inflammatory conditions, such as interstitial cystitis.
      We examined the effect of multiple phospholipase A2 and cyclooxygenase inhibitors
      on the immediate release of prostacyclin from human bladder microvascular
      endothelial cells. MATERIALS AND METHODS: We stimulated confluent human bladder
      microvascular endothelial cell monolayers with thrombin or tryptase and measured
      the immediate release of prostacyclin. Human bladder microvascular endothelial
      cells were pretreated with several selective phospholipase A2 and cyclooxygenase
      inhibitors before thrombin or tryptase stimulation to determine which combination
      of phospholipase A2/cyclooxygenase isoforms was involved in this process.
      Phospholipase A2 activity was measured using (16:0, [3H]18:1) plasmenylcholine
      substrate in the absence of calcium. [3H] arachidonic acid release was measured
      in the surrounding medium from prelabeled human bladder microvascular endothelial
      cell monolayers. Prostacyclin release into the surrounding medium was measured
      using a commercially available immunoassay kit. RESULTS: The immediate increase
      in prostacyclin release from thrombin or tryptase stimulated human bladder
      microvascular endothelial cells depended on the activation of membrane associated
      calcium independent phospholipase A2, resulting in an increase in arachidonic
      acid production. Constitutively active cyclooxygenase-1 was then responsible for
      further metabolism of free arachidonic acid to prostacyclin. CONCLUSIONS: These
      results show that the search for a suitable anti-inflammatory agent that
      selectively target specific phospholipase A2 isoforms requires rigorous testing
      in several cell types in response to various stimuli.

PMID- 16952711
TI  - Lipid peroxidation activates mitogen-activated protein kinases in testicular
      ischemia-reperfusion injury.
AB  - PURPOSE: Testicular damage after torsion has been attributed to many mechanisms,
      of which one is lipid peroxidation of the plasma membrane, which could cause the
      activation of the mitogen-activated protein kinase family. These proteins are of
      vital importance for signal transduction pathways and 2 of them, extracellular
      signal-regulated kinase and c-jun N-terminal kinase, participate in the
      pathogenesis of testicular ischemia. We investigated whether lipid peroxidation
      may trigger mitogen-activated protein kinase activation in testicular ischemia
      reperfusion. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were subjected
      to 1-hour testicular ischemia, followed by 24 hours of reperfusion. Sham
      testicular ischemia-reperfusion rats served as controls. Animals were randomized
      to receive raxofelast, an inhibitor of lipid peroxidation (20 mg/kg
      intraperitoneally administered 15 minutes before detorsion and 15 minutes after
      detorsion) or vehicle (1 ml/kg 10% dimethyl sulfoxide/NaCl solution). A group of
      animals was sacrificed 0, 10, 15, 20, 25 and 30 minutes, and 1, 2 and 3 hours,
      respectively, after detorsion to evaluate testicular c-jun N-terminal kinase,
      extracellular signal-regulated kinase and tumor necrosis factor-alpha activation
      by Western blot analysis, and mRNA expression and conjugated dienes using a
      spectrophotometer technique. Another group was sacrificed 24 hours after
      detorsion to evaluate histological alterations. RESULTS: Testicular ischemia
      reperfusion injury caused a significant increase in the conjugated diene levels,
      extracellular signal-regulated kinase c-jun N-terminal kinase activity and tumor
      necrosis factor-alpha expression in both testes. Furthermore, histological
      examination revealed marked damage. Raxofelast inhibited these parameters and
      decreased histological damage. CONCLUSIONS: These data suggest that lipid
      peroxidation triggers extracellular signal-regulated kinase and c-jun N-terminal
      kinase activation. Furthermore, mitogen-activated protein kinase blockade might
      represent a potential therapeutic approach to treatment in patients with
      unilateral testicular torsion.

PMID- 16952712
TI  - Qualitative and quantitative expression profile of muscarinic receptors in human
      urothelium and detrusor.
AB  - PURPOSE: We compared the complete spectrum of receptor subtypes expressed by
      human detrusor and its primary culture with the expression profile in a human
      urothelium immortalized cell line, and in fresh urothelium tissue and its primary
      cell culture. MATERIALS AND METHODS: The levels of mRNA expressed for receptor
      subtypes M1 through M5 were determined with reverse transcriptase-polymerase
      chain reaction and quantitative polymerase chain reaction in total RNA extracted
      individually from different human bladder specimens, including fresh tissue of
      human urothelium and detrusor, and their respective primary cultures, as well as
      from the UROtsa cell line. RESULTS: All 5 muscarinic receptors were detected in
      fresh human bladder tissue by reverse transcriptase-polymerase chain reaction
      RNA. The same was true in separated urothelium and detrusor tissue except for the
      lack of the M5 receptor transcript. Receptor subtype mRNA expression in the
      UROtsa cell line paralleled expression in fresh human bladder. Quantitative
      polymerase chain reaction data further corroborated these results and showed
      comparable mRNA expression for M2 and M3 in primary detrusor cultures. Primary
      cultures also had a decreased copy number of receptor genes than native tissue.
      The decrease was even more pronounced in primary urothelium culture and the
      UROtsa cell line in the presence of high calcium. M2 and M3 receptors were also
      detected in urothelium and detrusor by immunoreactivity. CONCLUSIONS: We
      identified all 5 existing muscarinic receptor subtypes in detrusor and
      urothelium, and transcripts levels of M2 and M3 were comparable in detrusor.
      These results support an alternative site of action in urothelium for anti
      muscarinic drugs. Urothelial receptors should be considered in the design of
      future drugs for overactive bladder.

PMID- 16952713
TI  - Increased expression of heat shock protein 20 and decreased contractile stress in
      obstructed rat bladder.
AB  - PURPOSE: Bladder outlet obstruction induces detrusor hypertrophy and it can
      eventually lead to decreased bladder smooth muscle contractility. Heat shock
      protein 20 is the proposed mediator of force suppression in vascular smooth
      muscle. We investigated whether heat shock protein 20 could also mediate the
      decreased contractility observed in partially obstructed rat bladders. MATERIALS
      AND METHODS: Female Wistar rats (Harlan Laboratories, Indianapolis, Indiana) were
      randomized to partial urethral ligation or sham ligation. After 3 weeks the rats
      were sacrificed, and the bladders were harvested, frozen, homogenized and
      analyzed for heat shock protein 20 content by Western blot immunoreactivity. The
      content of myosin regulatory light chain, a constitutively expressed protein, was
      determined as a control. Bladder smooth muscle strips were dissected from some
      rats and mounted for force generation measurement. RESULTS: At cystectomy
      obstructed bladders were significantly heavier and had more residual urine
      compared to sham operated bladders. Heat shock protein 20 immunoreactivity was
      significantly increased a mean +/- 1 SEM of 1.9 +/- 0.3-fold in obstructed vs
      sham operated bladders. Control protein myosin regulatory light chain
      immunoreactivity did not significantly differ in obstructed and sham operated
      bladders. Maximal stress, that is force per cross-sectional area, was
      significantly decreased in obstructed vs sham operated bladders. Human bladder
      was found to express immunoreactive heat shock protein 20. CONCLUSIONS: We noted
      that partially obstructed rat bladders 1) express higher levels of heat shock
      protein 20 and 2) generate less stress than sham operated bladders. These data
      suggest the possibility that heat shock protein 20 over expression could at least
      partially mediate the decreased contractile activity observed with partial
      bladder outlet obstruction. The mechanism for increased heat shock protein 20
      expression is unknown but it may involve increased mechanical stress or hypoxia
      from urethral obstruction. Human bladder expressed immunoreactive heat shock
      protein 20, suggesting that a similar mechanism could potentially occur in
      humans. If confirmed in humans, patients with clinical conditions that result in
      detrusor hypocontractility could potentially benefit from pharmacological
      interventions aimed at inhibiting heat shock protein 20.

PMID- 16952714
TI  - Re: Samuel Pepys: a patient perspective of lithotomy in 17th century England.

PMID- 16952715
TI  - Re: phallic preserving surgery in patients with invasive squamous cell carcinoma
      of the penis.

PMID- 16952716
TI  - Re: a clinical trial with chimeric monoclonal antibody WX-G250 and low dose
      interleukin-2 pulsing scheme for advanced renal cell carcinoma.

PMID- 16952717
TI  - The clinical significance of loneliness: a literature review.
AB  - Satisfying social relationships are vital for good mental and physical health.
      Accordingly, we recommend that the alleviation and prevention of social
      relationship deficits be a key focus of clinicians. In this review, we focus on
      loneliness as a crucial marker of social relationship deficits and contend that
      loneliness should command clinicians' attention in its own right--not just as an
      adjunct to the treatment of other problems such as depression. With a particular
      focus on the adolescent developmental period, this review is organized into five
      sections: Drawing on developmental and evolutionary psychology theories, the
      nature of social relationships and the function they serve is first discussed. In
      the second section, loneliness is introduced as an exemplar of social
      relationship deficits. Here a definition of loneliness is provided, as well as an
      explanation of why it may pose a situation of concern. This is followed by a
      review of the prototypic features of loneliness through examination of its
      affective, cognitive, and behavioral correlates. The fourth section includes a
      review of theories related to the antecedent and maintenance factors involved in
      loneliness. Finally, methodological and theoretical considerations are addressed,
      and conclusions and proposals for future research directions are put forth.

PMID- 16952718
TI  - Complications of endoscopic and open carpal tunnel release.
AB  - PURPOSE: To compile the major complications of carpal tunnel surgery and compare
      reported complications for open and endoscopic techniques. METHODS: A literature
      assessment was performed for published complications of open and endoscopic
      carpal tunnel release procedures; 80 publications, representing a period from
      1966 through 2001, were reviewed. Complications were identified as neurapraxia;
      nerve, tendon, or artery injury; and wound infection or dehiscence that required
      antibiotics or additional operative care. Differences in the proportions of
      complications between carpal tunnel release procedures were explored with the use
      of Fisher exact tests. RESULTS: The literature review yielded 22,327 cases of
      endoscopic carpal tunnel release and 5,669 cases of open carpal tunnel release.
      For structural damage to nerves, arteries, or tendons, the incidence for open
      carpal tunnel release is 0.49% and for endoscopic methods (transbursal and extra
      bursal), 0.19%. This difference is statistically significant (P < .005; 2-tailed
      Fisher exact test) and suggests that the overall proportion of structural
      complications for open carpal tunnel release according to our complication
      selection criteria is greater than the overall proportion of complications for
      endoscopic carpal tunnel release. CONCLUSIONS: The proportion of complications
      for carpal tunnel release, performed through an endoscopic or open approach, is
      very low. Selection of an open versus an endoscopic approach on the basis of
      structural complications for nerve, arteries, or tendons is not supported by
      statistical analysis of published complications. LEVEL OF EVIDENCE: Level III,
      retrospective comparative therapeutic study.

PMID- 16952719
TI  - What do you do when you have a loose screw?
AB  - PURPOSE: This study seeks to compare the pullout strength of various anchor
      configurations in an osteoporotic bone model. We have tested and present here a
      technique designed to augment the pullout resistance of an anchor in poor-quality
      bone with the use of a second anchor as an interference fit; this report
      describes our in vivo results with this procedure. METHODS: Four groups of suture
      anchor constructs were tested. These included a single 5.0-mm Bio-Corkscrew
      (Arthrex, Naples, FL) (group I), a single 5.5-mm Bio-Corkscrew FT (fully
      threaded; Arthrex, Naples, FL) (group II), a single 6.5-mm Bio-Corkscrew
      (Arthrex, Naples, FL) (group III), and an interference fit of two 5.0-mm Bio
      Corkscrew suture anchors (group IV). Anchors were secured in a 10-lb/ft3
      polyurethane foam block to simulate osteoporotic bone. Each construct was cycled,
      then was pulled to failure with an Instron testing device (Instron, Canton, MA);
      measurements regarding cyclic displacement, yield load, and extension at yield
      load were recorded. During the in vivo portion of the study, the interference fit
      technique was performed in 18 shoulder arthroscopy cases in which a loose screw
      was a matter of concern. After the technique was performed, both anchors were
      pulled so their security could be assessed; cuff repair then proceeded normally.
      RESULTS: Biomechanical study: In terms of yield load, every anchor construct was
      significantly different from every other construct. Specifically, pullout
      strength increased significantly as follows: group I was the weakest against
      pullout (176 +/- 13 N), group III (223 +/- 17 N) was significantly stronger than
      group I, group II (247 +/- 12 N) was significantly stronger than group III, and,
      finally, group IV (305 +/- 16 N) was significantly stronger than group II. The
      only statistically significant difference in terms of cyclic displacement was
      that group IV (1.4 mm +/- 0.2) had significantly less displacement than group III
      (1.9 mm +/- 0.3). No significant differences in extension at yield load were
      observed among any of the groups. In vivo study: The interference anchor
      technique was used in 18 of 24 loose screw situations over a 6-month period. In
      all 18 of these cases (100%), a stable dual-anchor construct was achieved. All
      anchors were stable to the tug test, and none failed during knot tying or at any
      time during the procedure. CONCLUSIONS: From the perspective of strength against
      pullout, the strongest suture construct of those tested in the osteoporotic bone
      model was the dual-anchor-against-an-anchor interference fit construct. The next
      strongest anchor tested was the 5.5-mm Bio-Corkscrew FT, followed by the 6.5-mm
      Bio-Corkscrew, and, finally, the 5.0-mm Bio-Corkscrew. Each group was
      statistically different from every other group in terms of pullout strength. The
      interference fit construct was not only the strongest in vitro, but it performed
      well in the in vivo setting, offering the added benefit of additional sutures to
      be used for securing a cuff defect. This study gives the arthroscopic surgeon
      important data for use in planning what to do when a loose screw is encountered.
      CLINICAL RELEVANCE: Data from this study may be useful for the arthroscopic
      surgeon in choosing the proper anchor construct for osteoporotic bone. This study
      also lends support to the technique of press-fitting an anchor against an anchor
      in the loose screw situation.

PMID- 16952720
TI  - Arthroscopic Bankart repair in traumatic anterior shoulder instability using a
      suture anchor technique.
AB  - PURPOSE: The purpose of this study was to prospectively evaluate the surgical
      outcome of arthroscopic Bankart repair via suture anchors in patients with
      recurrent traumatic anterior shoulder instability with a minimum follow-up of 2
      years. METHODS: We included 54 consecutive patients without an osseous Bankart
      lesion of greater than 25% of the glenoid circumference with a mean age of 25.3
      years (range, 16 to 58 years) undergoing arthroscopic Bankart repair via suture
      anchors for traumatic anterior shoulder instability. The mean follow-up was 3.7
      years (range, 2.3 to 5.2 years) at the final follow-up examination. Patients were
      evaluated prospectively according to the rating scales of Rowe, the American
      Shoulder and Elbow Surgeons, and Constant and Murley. One patient was lost to
      follow-up. RESULTS: After 3.7 years, 4 patients had recurrent instability: 3 had
      redislocated and 1 had recurrent subluxations. Thus the overall redislocation
      rate was 7.5%. Of the 4 redislocators, 3 had a traumatic onset of the
      redislocation. All shoulder scores (Rowe, American Shoulder and Elbow Surgeons,
      and Constant and Murley) revealed highly significant improvements
      postoperatively. At final follow-up, 85.7% of patients had returned to their
      preoperative sports level. CONCLUSIONS: Our results in this series demonstrate
      the efficacy of arthroscopic Bankart repair with suture anchors for the treatment
      of recurrent traumatic anterior shoulder instability with respect to recurrence
      rate, range of motion, and shoulder function during a mean follow-up of 3.7
      years. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 16952721
TI  - The subscapularis footprint: an anatomic study of the subscapularis tendon
      insertion.
AB  - PURPOSE: Arthroscopic repair of the subscapularis tendon has become more
      prevalent in recent years. Tears of the subscapularis insertion can be measured
      arthroscopically when the size of the average subscapularis tendon insertion is
      known. This anatomic study was performed to measure the dimensions and describe
      the anatomy of the subscapularis footprint. METHODS: A total of 6 male and 6
      female shoulders were dissected down to the insertion of the subscapularis
      tendon. The insertion was demarcated, the tendon was detached, and the dimensions
      of the insertion site were measured. RESULTS: The footprint is the insertion of
      the subscapularis tendon onto the lesser tubercle. The shape of the footprint was
      characterized as resembling a human ear. The insertion is broad proximally and
      tapered distally and has a straight medial border that is almost parallel to the
      longitudinal axis of the humerus. The total average cephalocaudal height of the
      footprint was 25.8 mm (+/-3.2 mm). The total average width was 18.1 mm (+/-1.6
      mm). Average male cephalocaudal height was 26.7 mm (range, 22 to 32 mm), and
      width was 18.3 mm (range, 16 to 21 mm). Average female cephalocaudal height was
      24.8 mm (range, 22 to 29 mm), and width was 17.8 mm (range, 15 to 19 mm).
      Although the male footprint was slightly larger than the female footprint,
      differences were not statistically significant (P = .18 and .31 for height and
      width, respectively). CONCLUSIONS: An anatomic study was performed to determine
      the size of the footprint of the subscapularis tendon. We found that the average
      cephalocaudal height of the footprint was 25.8 mm, and the average width was 18.1
      mm. CLINICAL RELEVANCE: Subscapularis tears are now more frequently addressed
      arthroscopically. This anatomic study was performed to characterize the anatomy
      of the subscapularis footprint so that the surgeon can achieve a more anatomic
      repair.

PMID- 16952722
TI  - Arthroscopic debridement in the treatment of patients with isolated tears of the
      subscapularis.
AB  - PURPOSE: To evaluate the treatment of properly selected patients with isolated
      subscapularis tears by arthroscopic debridement and release of the long head of
      the biceps. METHODS: Eleven shoulders that had undergone arthroscopic debridement
      in the treatment of subscapularis tears were reviewed. In all patients, 3 months
      of appropriate nonoperative management had been unsuccessful. Patients were
      selected for arthroscopic debridement if the tear was thought to be irreparable,
      or if the patient was older and unwilling to participate in the rehabilitation
      required after repair had been completed. Mean age at surgery was 64 years. The
      mean time interval from onset of symptoms to surgery was 11 months. Seven tears
      were traumatic, and 4 were degenerative. Four tears involved the superior third
      of the subscapularis tendon, 2 involved the superior two thirds of the
      subscapularis tendon, and 5 were complete tears. Nine shoulders also had
      dislocation or subluxation of the long head of the biceps tendon; these patients
      underwent concomitant biceps tenotomy. Patients were evaluated clinically and
      radiographically at a mean 34-month follow-up (range, 24 to 48 months). RESULTS:
      The mean Constant score increased from 49 points preoperatively to 80 points
      postoperatively (P < .0001). Nine patients were satisfied or very satisfied with
      the results. Preoperatively, 2 patients had mild glenohumeral arthritis.
      Postoperatively, radiographs demonstrated no progression of arthritis and no new
      onset arthritis in these 2 patients. CONCLUSIONS: The combination of arthroscopic
      debridement and biceps tenotomy in the treatment of subscapularis tears with
      biceps disease in selected patients yields good objective improvement and a high
      degree of patient satisfaction. LEVEL OF EVIDENCE: Level IV, therapeutic case
      series.

PMID- 16952723
TI  - Arthroscopic stabilization in anterior shoulder instability: collision athletes
      versus noncollision athletes.
AB  - PURPOSE: Collision athletes have been reported to be at high risk of
      redislocation after stabilization for anterior shoulder instability. However, few
      studies have compared the results of arthroscopic stabilization with collision
      and noncollision athletes. The purposes of this study were to analyze clinical
      outcomes of arthroscopic anterior shoulder stabilization in athletes and to
      compare the results between collision and noncollision athletes. METHODS: A total
      of 29 athletes were enrolled in this study, including 14 collision athletes and
      15 noncollision athletes. Mean age at the time of operation was 21.1 years, and
      mean follow-up period was 62.1 months (range, 25 to 117 months). All shoulders
      underwent arthroscopic stabilization. RESULTS: Visual analogue scale score, Rowe
      score, and Constant score improved after surgery (P < .05), but no statistically
      significant difference was found between collision and noncollision groups (P <
      .05). In all, 19 athletes (65.5%) returned to near preinjury sports activity
      levels (90% or greater recovery) after operation. Five athletes (17.2%)
      experienced postoperative instability. One (3.4%) had subluxation and 4 (13.8%)
      had redislocation after surgery. Four cases in the collision group (28.6%) and 1
      in the noncollision group (6.7%) had postoperative subluxation or dislocation (P
      = .118). CONCLUSIONS: Arthroscopic stabilization for anterior instability of the
      shoulder is a reliable procedure with respect to shoulder function, range of
      motion, and postoperative return to sports activities in athletes. However, a
      high recurrence rate (17.2%) was observed among athletes. Compared with the
      noncollision group (6.7%), the collision group yielded a higher failure rate
      (28.6%) than was expected. LEVEL OF EVIDENCE: Level IV, prognostic case series.

PMID- 16952724
TI  - Bucket-handle meniscal lesions: magnetic resonance imaging criteria for
      reparability.
AB  - PURPOSE: The purpose of this study was to determine the accuracy of magnetic
      resonance imaging (MRI) in predicting knee bucket-handle meniscal tear (BHMT)
      reparability. METHODS: Twenty-eight patients who underwent knee arthroscopy by a
      single surgeon for BHMT with prior MRI examination were included. BHMTs were
      diagnosed by MRI based on the association of a displaced meniscal fragment on
      coronal images and one of the following three signs on sagittal slices: flipped
      meniscus sign, double posterior cruciate ligament, and meniscal fragment within
      the intercondylar notch. BHMT patients' MRIs were retrospectively reviewed
      independently to search for criteria of reparability by 2 observers with
      different degrees of experience in musculoskeletal radiology, and disagreements
      were arbitrated to consensus. The criteria for BHMT reparability were as follows:
      (1) rim width of less than 4 mm; (2) tear length of 1 cm or greater, regardless
      of total lesion length; and (3) generation of isosignals by the inner meniscal
      fragment and peripheral rim compared with the normal contralateral meniscus of
      the same knee. The first 2 criteria indicate an adequate meniscal lesion length
      in the vascularized zone (only the peripheral third), enabling meniscal healing
      after repair; the third criterion guarantees that the meniscus is
      nondegenerative. RESULTS: Of the BHMTs, 5 (17.9%) were arthroscopically reparable
      and 23 (82.1%) were not. Interpretation of magnetic resonance images correctly
      predicted reparability in 4 of 5 reparable BHMTs and irreparability in 22 of 23
      irreparable BHMTs (26/28 lesions). Interobserver agreement was good for the
      prediction of reparability (kappa = 0.7). CONCLUSIONS: These results suggest that
      knee BHMTs that are predicted to be reparable by MRI would have a high likelihood
      of actually being reparable. LEVEL OF EVIDENCE: Level II, development of
      diagnostic criteria on basis of consecutive patients and gold standard.

PMID- 16952725
TI  - Meniscal repair with the RapidLoc meniscal repair device.
AB  - BACKGROUND: The RapidLoc is an all-inside, self-adjusting, flexible meniscal
      repair device that combines a suture with an anchor component and, by using a
      reinforced sliding knot, allows for tightening to compress and hold the repaired
      meniscal segments. The purpose of this study was to evaluate the clinical success
      of the RapidLoc device. METHODS: A prospective consecutive series of meniscal
      repairs performed with the RapidLoc device was studied. Lysholm, Tegner,
      Cincinnati, IKDC (International Knee Documentation Committee) activity scores,
      clinical examination findings, and adverse events were recorded on all patients.
      Associated procedures were recorded. An accelerated postoperative rehabilitation
      program was followed, independent of whether anterior cruciate ligament (ACL)
      surgery was also performed. RESULTS: A total of 32 patients underwent 32 meniscal
      repairs, with an average follow-up of 31 months (18 to 48 months). In all, 23
      repairs were done in conjunction with ACL reconstruction, and 9 repairs were
      carried out in stable knees. Repairs were made to 25 medial menisci and 7 lateral
      menisci. Tears repaired consisted of peripheral longitudinal tears with an
      average length of 2 cm (range, 15 to 30 mm). Four failures (12.5%) were
      arthroscopically documented. Clinical success occurred in 87.5% at the time of
      last follow-up. At follow-up, mean Tegner score was 5.1 (2.8 preoperative), IKDC
      activity score was 3.1 (1.8 preoperative), Lysholm score was 93.6 (48.4
      preoperative), and mean Cincinnati score was 88.1 (43.7 preoperative). The most
      common adverse event was cutting of the suture during RapidLoc insertion. One
      patient had excoriation and grooving of the medial femoral condyle associated
      with failed repair. Another patient developed a postoperative infection.
      CONCLUSIONS: The early clinical success rate was 87.5% with the RapidLoc device.
      Chondral grooving was observed in a single case. LEVEL OF EVIDENCE: Level IV,
      therapeutic case series.

PMID- 16952726
TI  - Arthroscopic resection of the discoid lateral meniscus: long-term follow-up for
      16 years.
AB  - PURPOSE: Although the clinical outcome of arthroscopic resection for a torn
      discoid lateral meniscus is known to be successful in the short term, long-term
      successful results are necessary. We reviewed the clinical results of
      arthroscopic meniscectomy for a torn discoid lateral meniscus in 29 knees, with
      an average follow-up of 16 years. METHODS: Subjective symptoms were evaluated
      with the use of a questionnaire developed by the International Knee Documentation
      Committee (IKDC). The trends of IKDC scores and patient age at the time of
      surgery were statistically evaluated through a stepwise piecewise linear
      regression analysis. Radiographic examination was performed in 15 knees. RESULTS:
      The average IKDC score was 87 points. Statistical analysis conducted with the use
      of a regression model of scores revealed that the regression line declined from
      90 to 72 points at ages between 25 and 30 years at the time of surgery.
      Radiographic examination revealed that patients with degenerative changes at the
      lateral joint compartment, such as joint space narrowing and subchondral
      sclerosis, were of greater average age at the time of surgery than did patients
      who did not develop these changes. CONCLUSIONS: Results suggest that clinical
      outcomes associated with this method are successful for longer than 10 years for
      patients younger than 25 years of age; however, older patients may develop
      problems caused by degenerative changes that may result from increased stress on
      the affected joint compartment. LEVEL OF EVIDENCE: Level IV, therapeutic case
      series.

PMID- 16952727
TI  - Purely intra-articular versus general anesthesia for proposed arthroscopic
      partial meniscectomy of the knee: a randomized controlled trial.
AB  - PURPOSE: The aim of this study was to compare intra-articular anesthesia alone
      versus general anesthesia with regard to ease of the procedure, level of
      postoperative pain, and patient satisfaction when partial meniscectomy is
      anticipated. METHODS: We prospectively randomized to general anesthesia or to
      intra-articular anesthesia 107 patients who were about to undergo knee
      arthroscopy, in whom partial meniscal resection was anticipated on the basis of
      clinical or radiologic grounds. Technical difficulty of the procedure, level of
      postoperative pain and nausea, and overall patient satisfaction were assessed.
      RESULTS: The ease of obtaining arthroscopic views, the adequacy of these views,
      and the ease of performing partial meniscal resection or another procedure were
      similar in both groups according to scores assigned by the operating surgeon.
      Pain at 6 hours postoperatively was significantly less in the intra-articular
      anesthesia group but was similar in the 2 groups at 24 and 48 hours. Patients who
      were given intra-articular anesthesia reported higher satisfaction rates in
      understanding the underlying disease of the knee. CONCLUSIONS: We propose that
      intra-articular anesthesia alone can be effectively used in knee arthroscopies in
      which partial meniscal resection is anticipated. LEVEL OF EVIDENCE: Level I, high
      quality randomized controlled therapeutic trial.

PMID- 16952728
TI  - Outpatient arthroscopic knee surgery under multimodal analgesic regimens.
AB  - PURPOSE: To investigate whether diclofenac could be used in preemptive and
      multimodal fashion with local anesthesia (LA) during arthroscopic knee surgery.
      METHODS: A cohort of 628 patients (age range, 14 to 60 years) underwent
      outpatient arthroscopic knee surgery under LA with 15 mL of 2% lidocaine with
      epinephrine. Diclofenac 1 mg/kg was administered immediately before the procedure
      was performed. Pain was intraoperatively assessed with a 10-cm visual analogue
      scale (VAS). Patients' and surgeons' satisfaction with the quality of anesthesia
      was estimated by a special questionnaire and VAS score. RESULTS: From the
      technical point of view, arthroscopic procedures were successfully completed in
      98.2% of patients. Pain experienced during injection of lidocaine (VAS score:
      median, 2.9; mean, 3.4; standard deviation [SD], 3.2; range, 0 to 10) was more
      severe (P = .0001) than pain experienced during the surgical procedure itself
      (VAS score: median, 1.8; mean, 2.4; SD, 2.2; range, 0 to 5.2). Arthroscopy was
      well tolerated by most patients (98.5%), and only 1.4% of procedures had to be
      terminated prematurely because of patient discomfort. Almost 95.7% of patients
      reported that they would undergo the same procedure again under the same type of
      anesthesia. In 4.7% of patients, LA was not considered optimal by the performing
      surgeon. CONCLUSIONS: Arthroscopic knee surgery with diclofenac and LA with no
      premedication is an efficient and well-tolerated method used in outpatient
      practice with no major adverse effects. LEVEL OF EVIDENCE: Level IV, therapeutic
      case series.

PMID- 16952729
TI  - Morphology of anterior cruciate ligament attachments for anatomic reconstruction:
      a cadaveric dissection and radiographic study.
AB  - PURPOSE: To define the positions of the attachments of the anteromedial (AM) and
      posterolateral (PL) bundles of the anterior cruciate ligament (ACL). METHODS: The
      shape and positions of the femoral and tibial attachments of the 2 bundles
      relative to bony landmarks were measured in 7 fresh-frozen, unpaired cadaveric
      knees by 6 independent observers. Metallic marker beads were then inserted into
      the defined anatomic points, and plain radiographs of the specimens were taken.
      We used the line described by Amis and Jakob on the tibia and the grid prepared
      by Bernard et al. for the femur to define AM and PL bundle attachment positions.
      RESULTS: In the cadaveric specimens, referencing the position of the AM bundle
      tibial attachment from the retro-eminence ridge (RER) resulted in the least
      interobserver error. On tibial radiographs, the distance between the posterior
      tibial cortex and the perpendicular projection of the center of the AM bundle
      attachment onto Amis and Jakob's line was 35.6 +/- 5.1 mm. The ratio of this
      distance to the length of Amis and Jakob's line (from the anterior cortex) was
      36% +/- 3.8% (and 52% +/- 3.4% for the center of the PL bundle). On the femur,
      the center of the AM bundle was situated at 26.4% +/- 2.6%, and the center of the
      PL bundle at 32.3% +/- 3.9%, along the length of Blumensaat's line. CONCLUSIONS:
      The RER provides an easily identifiable and accurate reference point that can be
      used clinically. On a lateral radiograph, the positions of the tibial attachments
      can be referenced to Amis and Jakob's line. This method, different from
      Blumensaat's line, is independent of knee flexion. CLINICAL RELEVANCE: This study
      details anatomically and radiologically the positions of the attachments of the
      AM and PL bundles of the ACL. This could assist with accurate tunnel placement in
      reconstruction surgery and provide reference data for postoperative radiographic
      evaluation.

PMID- 16952730
TI  - Prospective evaluation of patellar tendon graft fixation in anterior cruciate
      ligament reconstruction comparing composite bioabsorbable and allograft
      interference screws.
AB  - PURPOSE: Bioabsorbable interference screws have proved to be biologically safe
      and to provide adequate graft fixation. Metallic interference screws have
      therefore been continuously replaced over the years. However, degradation times
      are highly variable, and bony replacement of the screw does not always occur in
      human beings. Composite interference screws have recently been introduced to
      enhance bony integration. We evaluated 2 different composite interference screws
      and compared them with an allograft interference screw over a 2-year period after
      anterior cruciate ligament (ACL) reconstruction with an autologous bone-patellar
      tendon-bone graft. METHODS: Three groups of patients were prospectively
      evaluated. Poly-L-lactid acid/hydroxyapatite composite screws (BioRCI-HA; Smith &
      Nephew, Andover, MA) (group A), poly-L-lactid acid/beta-tricalcium phosphate
      composite screws (Bilok; Atlantech, Radevormwald, Germany) (group B), or
      allograft interference screws (CorlS; Regeneration Technologies, Alachua, FL)
      (group C) were used for tibial fixation of a patellar tendon autograft in ACL
      reconstruction. Each group consisted of 20 patients (mean age, 32.2 +/- 10.9
      years in group A, 32.3 +/- 10.6 years in group B, and 31.1 +/- 6.6 years in group
      C) with no significant (P < .05) differences in age, sex, and time of follow-up.
      Subjective and clinical International Knee Documentation Committee parameters
      were evaluated preoperatively and at 3, 12, and 24 months postoperatively;
      computed tomography scans were obtained postoperatively and at 3, 12, and 24
      months; and magnetic resonance imaging (MRI) scans were obtained at 3 and 24
      months postoperatively. RESULTS: Screw breakage during insertion occurred in 2
      cases (1 in group A and 1 in group B). There was no significant (P < .05)
      difference in subjective and clinical results at any time of follow-up. No
      inflammatory response could be detected on MRI in any of the patients in all
      groups. Computed tomography scans documented complete bone block incorporation at
      3 months in all groups. Both composite interference screws showed signs of
      degradation but were still clearly visible 24 months after ACL reconstruction. At
      12 months, a sclerotic rim around the screw cavity could be outlined in group B
      only. No bony replacement had taken place up to 24 months postoperatively in
      group A or B. In group C the allograft bone screw was completely integrated and
      barely visible after 24 months. CONCLUSIONS: All 3 screw types provided adequate
      graft fixation and were associated with excellent clinical results and no
      inflammatory response on MRI. Ultimately, a resorbable screw has to be replaced
      by bone to facilitate revision surgery. Formation of a sclerotic rim around the
      outline of the screw makes later bony replacement (group B) unlikely. After 24
      months, complete bony integration had only taken place when allograft screws were
      used. CLINICAL RELEVANCE: At 24 months, no advantage of composite screw materials
      over conventional bioabsorbable screws could be detected. If composite materials
      will be of any advantage with respect to bony replacement has to be observed with
      longer-term follow-up. The allograft bone screw was completely incorporated and
      replaced by cancellous bone after 24 months. Unfortunately, the screw's more
      complicated handling, higher cost, and limited availability impair the
      possibilities for its standard clinical use.

PMID- 16952731
TI  - Anatomic double-bundle anterior cruciate ligament reconstruction.
AB  - Anterior cruciate ligament (ACL) reconstruction is one of the most common
      procedures performed by orthopaedic surgeons. The procedure has improved
      significantly since its inception in 1900 and continues to be intensively studied
      with outcomes receiving considerable attention. Traditional ACL reconstruction
      techniques have focused on one portion of the ACL--the anteromedial bundle.
      Single-bundle ACL reconstruction is the criterion standard and has provided good
      to excellent results, with many athletes being able to return to sports; however,
      recently, some authors have noted persistent instability with functional testing
      and degenerative radiographic changes after single-bundle ACL reconstruction. As
      a result, several centers have attempted to improve upon the single-bundle
      technique by reconstructing both the anteromedial and posterolateral bundles of
      the ACL. This article will present the embryologic, anatomic, and biomechanical
      rationale for double-bundle ACL reconstruction. In addition, the latest outcomes
      of double-bundle ACL reconstruction will be presented.

PMID- 16952732
TI  - Arthroscopic suprascapular nerve decompression at the suprascapular notch.
AB  - The suprascapular notch is a common location for entrapment of the suprascapular
      nerve. Open surgical procedures for excision of the transverse scapular ligament
      are associated with pain relief and functional improvement. Arthroscopic
      procedures have been described for decompressing ganglion cysts, which compress
      the nerve at the spinoglenoid notch. However, there is no description of an
      arthroscopic procedure for decompression of the nerve at the suprascapular notch,
      and this is probably related to unfamiliarity with the complex anatomy of the
      region. The technique described herein is based on standard anatomic landmarks
      and utilization of these as reference points for arthroscopic orientation and
      reproducibility. The acromioclavicular joint, conoid ligament, and coracoid
      process are stepwise reference landmarks leading to the suprascapular notch.
      Arthroscopic identification of structures around the notch is necessary before
      ligament resection. A new suprascapular portal, in combination with an accessory
      portal, is described for retraction, blunt dissection, nerve stimulation, and
      ligament resection. Key instruments include a 4-mm arthroscope of standard length
      (160 mm), with a 70 degree angled lens for adequate visualization and a
      calibrated probe to guide and limit dissection.

PMID- 16952733
TI  - Arthroscopic subscapularis repair: surgical tips and pearls A to Z.
AB  - Arthroscopic subscapularis repair can be technically challenging. This article
      summarizes a number of technical tips that can greatly simplify and expedite what
      otherwise might be a daunting surgical procedure. Specific tips and pearls
      include the following: 1. A description of a new clinical test--the bear-hug test
      -for detecting subscapularis tears on physical examination. 2. How to accurately
      place portals for precise subscapularis repair. 3. How to safely and accurately
      perform a coracoplasty. 4. How to identify and mobilize a retracted subscapularis
      tear. 5. How the comma sign can be used to simplify arthroscopic subscapularis
      repair. 6. How to securely repair all sizes of subscapularis tear. 7. A
      description of postoperative immobilization and rehabilitation to optimize
      results of arthroscopic subscapularis repair.

PMID- 16952734
TI  - Electrosurgical arthroscopic patellar denervation.
AB  - Patellofemoral pain depends on many pathophysiologic factors and may be difficult
      to manage. It often occurs with no apparent cause in young persons. A new
      arthroscopic technique based on anatomic and pathophysiologic studies is
      described here for the treatment of patients with patellofemoral pain and no or
      minimal malalignment. Nociceptive receptors are richly distributed in the
      peripatellar soft tissue. We surmised that a thermal lesion to this region would
      lead to desensitization of the anterior knee area, referred to as patellar
      denervation. With the leg in maximum extension, the electrocoagulator is inserted
      through a combined anterointernal and suprapatellar approach to access the entire
      perimeter of the patella. A simple thermal lesion to the peripatellar soft tissue
      in the region closest to the patella is enough to obliterate a considerable
      number of nociceptive receptors. This thermal lesion should not include the
      region of the patellar tendon because this is an important site of entry for
      vessels reaching the patella, and injury to these vessels may cause patellar
      necrosis. Patellar denervation achieved through this simple technique may offer a
      solution for patients with intractable patellofemoral pain with no evident
      alterations.

PMID- 16952736
TI  - Diagnostic imaging and arthroscopy.

PMID- 16952738
TI  - Epidemiology and risk factors for colorectal dysplasia and cancer in ulcerative
      colitis.
AB  - Patients with UC are at increased risk of CRC, but a series of population-based
      studies published within the past 5 years suggest that this risk has decreased
      over time. The crude annual incidence rate of CRC in UC ranges from approximately
      1 in 500 to 1 in 1600. In some cohorts, an elevated risk of CRC relative to the
      general population can no longer be demonstrated. The exact mechanism for this
      decrease in risk remains unclear but may be attributable to a combination of more
      widespread use of maintenance therapy and surveillance colonoscopy as well as
      more judicious reliance on colectomy. In addition to the classic risk factors of
      increased extent and duration of UC, it seems that PSC, a family history of
      sporadic CRC, severity of histologic bowel inflammation, and young age at colitis
      onset are independent risk factors for cancer.

PMID- 16952739
TI  - Pathology of dysplasia and cancer in inflammatory bowel disease.
AB  - Morphologic identification of dysplasia in mucosal biopsies is the best and most
      reliable marker of an increased risk for malignancy in patients who have
      inflammatory bowel disease, and it forms the basis of the recommended endoscopic
      surveillance strategies that are in practice for patients who have this illness.
      In ulcerative colitis (UC) and Crohn's disease (CD), dysplasia is defined as
      unequivocal neoplastic epithelium that is confined to the basement membrane,
      without invasion into the lamina propria. Unfortunately, unlike in UC, only a few
      studies have evaluated the pathologic features and biologic characteristics of
      dysplasia and carcinoma in CD specifically. As a result, this article focuses
      mainly on the pathologic features, adjunctive diagnostic methods, and
      differential diagnosis of dysplasia in UC.

PMID- 16952740
TI  - Molecular biology of dysplasia and cancer in inflammatory bowel disease.
AB  - Colorectal cancer (CRC) develops from a dysplastic precursor lesion, regardless
      of whether it arises sporadically, in the setting of high-risk hereditary
      conditions, or in the context of chronic inflammation like inflammatory bowel
      disease (IBD). This review focuses on the molecular alterations associated with
      CRC pathogenesis in IBD. Although none of the molecular alterations to be
      discussed have yet been integrated into clinical practice, there is potential for
      molecular diagnostics to enhance the management of patients with long-standing
      IBD.

PMID- 16952741
TI  - Natural history and management of flat and polypoid dysplasia in inflammatory
      bowel disease.
AB  - Dysplasia can be a marker that cancer is already present or is coming in the near
      future. Hence, Physicians should not be cavalier in approach to finding it or in
      approach after it is found, whether it is in flat mucosa or raised mucosa. Low
      grade dysplasia should garner similar respect to high-grade dysplasia, if for no
      other reason than the difficulty that expert pathologists have with
      distinguishing low-grade dysplasia from high-grade dysplasia. There is no sure
      way to reduce the likelihood that dysplasia will arise in UC. Some investigators
      have promoted the use of 5-ASA. This topic is covered in greater detail elsewhere
      in this issue (see article by Rubin and Kavitt elsewhere in this issue); however,
      there is no definitive evidence that 5-ASA can reduce cancer incidence.

PMID- 16952742
TI  - Surveillance for cancer and dysplasia in inflammatory bowel disease.
AB  - There remain technical challenges to the accurate prediction and diagnosis of
      neoplasia in IBD; therefore, prevention strategies are based on limited evidence
      and instead, consensus opinions and guidelines. Existing guidelines and published
      expert opinions are in agreement that given the increased risk of cancer in IBD
      and well-described associated risks, prevention strategies are warranted. The
      preponderance of existing prevention is focused on secondary prevention by
      performance of screening and surveillance colonoscopies with random biopsies to
      identify neoplasia and trigger surgical resection for prevention of invasive
      cancer and death. Substantial technical and practical challenges remain, however,
      and there is a great need for improved understanding of the compounded risks of
      neoplasia, the natural history of dysplasia, and more accurate detection and
      diagnostic techniques. A future approach to prevention is likely to stratify
      patients based on individualized risks that include, among things, the histologic
      degree of inflammation present. In meantime, existing guidelines should be
      emphasized and ongoing education of clinicians and patients must occur.

PMID- 16952743
TI  - Chromoendoscopy and other novel imaging techniques.
AB  - The newly developed high-resolution and magnification endoscopes offer features
      that allow more and new mucosal details to be seen. They are commonly used in
      conjunction with chromoendoscopy. The analysis of mucosal surface details is
      beginning to resemble histologic examination. More accurate recognition of small
      flat and depressed neoplastic lesions is possible. Endoscopic prediction of
      neoplastic and nonneoplastic tissue is possible by analysis of surface
      architecture of the mucosa, which influences the endoscopic management. For the
      diagnosis of flat adenomas, chromoendoscopy should be a part of the endoscopist's
      armamentarium. In inflammatory bowel disease, chromoendoscopy can be used for
      patients with long-standing UC to unmask flat intraepithelial neoplasia and is
      likely to become the new standard method for surveillance colonoscopy in the near
      future. The new detailed images seen with magnifying chromoendoscopy are the
      beginning of a new era in which advances in optical development, such as confocal
      endomicroscopy, allow a unique look at detailed cellular structures.

PMID- 16952744
TI  - Cancer in Crohn's disease.
AB  - There has been a multitude of case reports, case series, hospital-based, and
      population-based studies that link CD to various types of cancers. When each of
      these studies is scrutinized, however, there is only enough evidence to support a
      link between colorectal adenocarcinoma, SBA, and squamous and adenocarcinomas
      that are associated with perianal fistulizing disease. All of the studies of
      large bowel adenocarcinoma or SBA follow patients in an era during which there
      were far fewer effective medicines to treat CD and surgery was more commonplace.
      The only surveillance study of patients who had extensive, long-duration Crohn's
      colitis showed a 22% risk for developing neoplasia (low-grade, high-grade, or
      cancer) after four surveillance examinations. Overall results from this study and
      the multitude of the other studies show that the risk for cancer in Crohn's
      colitis is equal to that in UC given equal extent and duration of disease.
      Patients who have Crohn's colitis that affects at least one third of the colon
      and with at least 8 years of disease should undergo screening and surveillance,
      just as in UC. Although the absolute risk for SBA in CD is low (2.2% at 25 years
      in one study), we should not rule out screening and surveying for this
      complication that is associated with significant morbidity and mortality in
      patients who have long-standing, extensive, small bowel disease. The risk for
      lymphoma and leukemia in CD is low, but immunomodulators and biologics may
      increase this risk. The evidence that links carcinoid tumors to CD is weak, and
      population-based studies need to be done. The study of cancers that are
      associated with CD is an evolving field that surely will change given that
      immunomodulators and biologics are being used with greater frequency.

PMID- 16952745
TI  - Surgical approaches to cancer in patients who have inflammatory bowel disease.
AB  - IBD clearly increases the risk for GI malignancies, especially CRC. The absolute
      number of patients that develops such malignancies is low compared with the
      overall cancer rate; however, younger age of onset, higher relative risk, unique
      clinical presentations, and problems with early diagnosis make this a serious
      complication of IBD. With the exception of patients with comorbid complications,
      such as primary sclerosing cholangitis, the prognosis is no worse for CRCs that
      arise as the result of IBD compared with those that arise sporadically. The
      prognosis remains poor for small bowel adenocarcinomas in patients who have CD,
      primarily because of their advanced stage at detection. Diligent surveillance is
      essential for early detection and treatment of IBD-related CRCs in patients with
      unresected colons, long-standing or extensive disease, and in those who have
      early-onset CD, although pundits still question whether it significantly affects
      prognosis and survival. Better surveillance techniques for small bowel dysplasia
      or malignancy in patients who have CD is needed, especially given the poor
      prognosis of these patients when advanced cancers are detected. Depending on the
      presentation and disease diagnosis, patients have several surgical treatment
      options and can expect good outcomes for all. When the appropriate surgical
      technique is used in patients who have colon or rectal cancer, along with
      adjuvant chemotherapy when appropriate, prognosis and function is good; however,
      the experience of the surgeon can affect the prognosis for IBD-related GI
      cancers. Surgical therapy is based not only on general oncologic principles, but
      also on the surgery that is appropriate for the IBD diagnosis. Resection of the
      mesentery and lymphadenectomy should be performed according to oncologic
      principles. Postoperative survival for IBD-related CRC is good, and diligent
      surveillance and follow-up are critical to the patient's overall prognosis.

PMID- 16952746
TI  - Chemoprevention: risk reduction with medical therapy of inflammatory bowel
      disease.
AB  - The ideal chemopreventative agent, in addition to being efficacious in the
      prevention of cancer, must be easily administered, affordable, safe, and well
      tolerated, with minimal side effects. In the past decade, a growing body of
      literature has emerged on the prevention of CRC in patients with long-standing CD
      and UC. The data are not definitive and consist almost exclusively of
      retrospective case-control and cohort studies rather than the more rigorous
      prospective RCTs. 5-ASA compounds have been most thoroughly studied, and most of
      the existing data support the use of 5-ASA in the prevention of CRC. Although the
      precise dose and duration are unclear, studies suggest that chronic systemic
      administration of 5-ASA at a dose of at least 1.2 g/d is most likely to be
      effective. A beneficial effect of folate, albeit not statistically significant,
      has been consistently shown in every study performed for this purpose. Folate
      supplementation, which is safe and affordable, should also be recommended for all
      patients with IBD, especially those taking sulfasalazine. UDCA has been shown to
      exert a protective effect in most studies on patients with UC and concomitant
      PSC. Because this patient population is at particularly high risk for CRC, it is
      advisable to consider UDCA in all patients with colitis complicated by PSC. For
      patients without PSC, sufficient data do not exist to recommend it for the
      purpose of cancer prevention. Five of the six corticosteroid studies have found a
      beneficial effect of systemic steroids, although most did not reach statistical
      significance. Regardless, given the frequent and serious adverse effects
      associated with chronic steroid use, systemic corticosteroids should not be
      prescribed for this indication. Budesonide, an oral corticosteroid with minimal
      systemic absorption, is a potential alternative, although it has not yet been
      studied as a chemopreventative agent. Similarly, until the long-term safety of
      chronic NSAID use can be demonstrated in patients with IBD, the role of NSAIDs in
      chemoprevention remains undefined. Although the data are conflicting, immune
      modulating medications, such as AZA, do not seem to confer any reduction in the
      risk of dysplasia or CRC. The data on calcium supplementation and statin use are
      still too limited to endorse their use for the prevention of colitis-related CRC.
      Chemoprevention is an area that holds great promise in the reduction of morbidity
      and mortality associated with IBD. Further studies, including prospective trials
      when possible and cost-effectiveness analyses, need to be performed to develop an
      optimal strategy for the reduction of cancer risk in patients with IBD.

PMID- 16952747
TI  - Systemic treatment of patients who have colorectal cancer and inflammatory bowel
      disease.
AB  - Colorectal cancer is the most common malignant complication in patients who have
      IBD. The disease is difficult to diagnose because there is an overlap in symptoms
      in patients who have colon cancer and those who have IBD. Much has been learned
      about the incidence of colorectal cancer in patients who have IBD and its
      correlation with disease activity, duration, and anatomic location; however,
      almost no data are available regarding specific therapeutic considerations during
      adjuvant or palliative chemotherapy for these patients with respect to their
      underlying disease. Patients who have IBD who develop colorectal cancer are at
      higher risk for developing severe diarrhea during chemotherapy that may be due to
      the toxic effects of cytotoxic drugs or a flare of the IBD. Continuous infusional
      5-FU alone, in combination with leucovorin, or in combination with oxaliplatin
      (FOLFOX) seems to be tolerated best. Bolus infusions of 5-FU (Roswell Park or
      Mayo regimens) and combination therapy of irinotecan with 5-FU should be avoided
      because of severe diarrhea and the possibility of sepsis. When diarrhea develops
      or worsens, empiric aminosalicylates may be given. Although it is theoretically
      possible that anti-EGFR therapies could affect IBD activity adversely, clinical
      experience with cetuximab in patients who have colorectal cancer has not shown
      any significant gastrointestinal side effects. Therefore, it seems reasonable to
      use it in patients who have colorectal cancer and IBD. The administration of
      bevacizumab has been associated with rare episodes of intestinal perforation; it
      should be used with great care in patients who have IBD. More studies and an
      integrative, multidisciplinary approach from oncologists and gastroenterologists
      are needed to provide optimal care for patients who have IBD during chemotherapy
      for colorectal cancer

PMID- 16952750
TI  - Sport psychology: psychologic issues and applications.
AB  - This article has briefly highlighted the area of sport psychology as it relates
      to performance psychology skills (mental training), including a historical
      overview and current topics overview. The use of mental training skills may be of
      interest to the practicing physical medicine and rehabilitation professional in
      the treatment of his or her patients. It is important that the physical medicine
      professional recognize what sport or performance psychology represents within the
      paradigm of psychologic interventions. Referring to an individual based on his or
      her training (licensed psychologist versus mental training consultant) is
      essential for the appropriate management of psychologic issues related to
      performance. The issues related to the psychologic rehabilitation of the injured
      athlete are of importance to the medical staff; the overview of affective
      responses can assist in understanding the normal and adaptive responses of the
      injured athlete. Finally, a brief description of a psychologist's role within a
      sports medicine and rehabilitation practice is presented. The psychologic issues
      that are present in the world of sport and elite performance are numerous, and
      not all are mentioned in this article. Issues of eating disorders, substance
      abuse, and psychologic health with athletes should be further explored within the
      physical medicine and rehabilitation discipline as well as in the sports medicine
      discipline. The ever-evolving psychologic dynamics of individuals involved in
      sport and elite performance are intriguing and unique. A specialized knowledge
      base, training, and experience in providing psychologic services are required to
      treat this unique population. Counseling and clinical issues of the athlete and
      elite performer require further attention in the realm of psychologic
      interventions, including further exploration of the efficacy of interventions for
      performance enhancement. The field of applied sport psychology may offer the
      physical medicine professional a unique perspective into the care of patients who
      are athletes and elite performers.

PMID- 16952751
TI  - Management of common running injuries.
AB  - Runners are susceptible to a variety of potential injuries because of the
      considerable stress of this activity. This can create a challenge for the
      treating practitioner; however, many of the common ailments occur in a reasonably
      predictable pattern. A careful history and physical examination are necessary for
      accurate diagnosis. Having a good understanding of these injuries as well of the
      role of biomechanical factors and common training errors can assist with
      appropriate care. Further development in the knowledge of soft tissue trauma,
      gait, and diagnostic and therapeutic modalities should lead to improved
      management of the injuries facing these athletes.

PMID- 16952752
TI  - Triathlon.
AB  - From its roots in San Diego to its Olympic debut in Sydney in 2000, triathlon has
      emerged as a popular sport with a wide variety of participants. Because of the
      nature of the sport, excessive training resulting in overuse injuries is common.
      Triathlon injuries can also be unique from the individual sports involved in that
      they are attributed to a cumulative effect of multi-sport training. Because many
      triathletes have not grown up participating in the individual sports,
      biomechanics in each of the disciplines must also be considered as a source of
      injury. Nutrition and environmental factors and the role that they play in the
      endurance athlete should also not be overlooked. The sport of triathlon is
      rapidly growing, and the ability to recognize the unique aspects of these
      injuries can help the multisport athlete to train properly and be healthier and
      more successful.

PMID- 16952753
TI  - Rehabilitation of basketball injuries.
AB  - Basketball is one of the most popular sports in the United States and throughout
      the world, and therefore represents one of the most common sources of sports
      related injuries. Basketball injuries should be managed by the same general
      rehabilitation principles as other sports injuries. Additionally, the clinician
      should be aware not only of general sports injuries but of those injuries most
      commonly seen in basketball players. By maintaining knowledge of the most common
      basketball injuries as well as their diagnosis and treatment, the clinician can
      help to optimize the athlete's return to play and enjoyment of the sport.

PMID- 16952754
TI  - Golf injuries and rehabilitation.
AB  - There are more than 25 million golfers in the united States, and many have an
      injury related to golf. Low back injuries are the most common golf injuries,
      followed by elbow injuries. Successful treatment of golf injuries often includes
      modification of the golf swing. Adaptations allow many individuals, including
      those who are physically challenged, to enjoy playing golf.

PMID- 16952755
TI  - Musculoskeletal injuries in tennis.
AB  - Tennis is popular in the United States, with millions participating in the sport.
      Unlike many other sports, young, middle-aged, and elderly persons are actively
      playing tennis. Most injuries that are seen are secondary to overuse. Faulty
      stroke mechanics are often involved in the development of specific injuries seen
      in tennis players. Fortunately, most injuries respond to conservative treatment
      and do not require surgery. Most players are able to return to their previous
      level of activity after appropriate treatment.

PMID- 16952756
TI  - Alpine climbing: injuries and illness.
AB  - Alpine climbing is a sport whose participants are at risk for a variety of
      injuries and illnesses. Climbers are venturing into the mountains and attempting
      routes with ever-increasing difficulty, and it is important to understand the
      injury and illness concerns of alpine climbers better. Alpine climbers are prone
      to injuries common to traditional mountaineers and more specialized sport rock
      climbers. Falls while climbing represent one of the more common causes of serious
      injury, although acute and chronic musculoskeletal injuries of the hands and
      extremities are also frequent afflictions. Alpine climbers are at risk for
      injuries and illness because of the mountain environment where they participate
      in their sport. Proper preparation for the cold is imperative to prevent
      frostbite and hypothermia. Worsening symptoms of headache or respiratory symptoms
      should always alert the alpine climber to possible altitude illness.
      Understanding the injuries common to the sport can allow providers to deliver the
      best medical care.

PMID- 16952757
TI  - The martial arts.
AB  - Given the increasing popularity of the martial arts, it is likely that physicians
      in all specialties encounter patients who participate. From pediatric patients,
      to geriatric patients, to those living with various disabilities, the martial
      arts may offer physical, psychologic, and therapeutic benefits. An appreciation
      of the physical demands of the martial arts is crucial to understanding the
      pathogenesis of injury as well as to planning treatment and prevention strategies
      and to determining safe return to participation after injury.

PMID- 16952758
TI  - Soccer.
AB  - Soccer has rules, regulations, and a style of play that is unlike any other
      sport. The characteristics of soccer, along with required functional activities,
      obviously place a significant demand on the physical and technical skills of each
      athlete. Consequently, many of the patterns of injuries and medical problems are
      unique. This article describes the physical demands of soccer; reviews the
      epidemiology; and discusses the mechanisms, pathologic findings, and treatment of
      soccer-related injuries and medical problems.

PMID- 16952759
TI  - Dance-related injury.
AB  - Although dance medicine has derived extensive knowledge from sports medicine,
      some aspects covered in the practice of dance medicine are unique to this field.
      Acute and overuse injuries must be analyzed within the scope of associated
      mechanisms of injury, mainly related to the practice of specific dance
      techniques. Even though most available medical literature concerning dance
      medicine is specific to ballet-related conditions, many of the concepts covered
      here and in other articles can be helpful in the treatment and diagnosis of
      participants in other dance disciplines. Continued research is expanding the
      knowledge on injury patterns of different dance disciplines. It is the experience
      of dance practitioners that dancers are quite in touch with their bodies; thus,
      when their ailments are systematically analyzed, and underlying cause can usually
      be identified. In this sense, it is evident that the principles of dance medicine
      and rehabilitation allow the practitioner to arrive at a diagnosis and treat the
      underlying causes to prevent reinjury, ameliorate sequelae from injury, and
      minimize residual deficits after injury.

PMID- 16952760
TI  - Fencing.
AB  - Fencing is a sport in which two people attempt to score points by making their
      weapon (epee, foil, or saber) contact their opponent. The most common types of
      injury seen in fencing are weapon injuries; strains, sprains, and trauma; and
      nontraumatic injuries, the pathologic findings of which are discussed in this
      article.

PMID- 16952761
TI  - Foreword.

PMID- 16952763
TI  - Depressive disorders in childhood and adolescence: an overview: epidemiology,
      clinical manifestation and risk factors.
AB  - The diagnostic category of depressive disorder in pediatric age is a relatively
      new concept that is rooted in empirical studies that date back to only the late
      1980s. This article discusses the current consensus nosology and epidemiology of
      unipolar depressive disorders in young age and the risk factors for depression
      onset and recurrence. There is also a brief overview of psychosocial and
      pharmacologic evidence-based therapies and suggested areas for future research.
      This article also contains a brief description of the items discussed in detail
      in this issue.

PMID- 16952764
TI  - Neurobiology of depression in children and adolescents.
AB  - This article reviews classical and updated studies of the neurobiology of
      depressive disorders in children and adolescents. Most studies of childhood and
      adolescent depression and suicide have followed up the observations and methods
      used in studies in adults. These studies include neuroendocrine studies, which
      particularly look at the hypothalamic-pituitary-adrenal axis, the serotonergic
      system, peripheral blood and cerebrospinal fluid biologic markers, genetics, gene
      environment interactions and sleep studies, and neuroimaging and postmortem
      studies, although in these areas the number of studies is limited.

PMID- 16952765
TI  - Twin studies in pediatric depression.
AB  - Pediatric depression is an important clinical problem that is known to be
      familial. Twin studies have been used not only to examine the genetic etiology of
      depression but also to investigate developmental changes and gender effects, the
      relationship of depression with anxiety, and increasingly, the interplay of
      genetic liability with environmental risk factors. There is evidence that
      pediatric depression symptom scores and clinical depression are genetically
      influenced, but results from different twin studies have varied. These studies
      also have demonstrated the important contribution of environmental risk factors.
      Some of the differences in findings may be caused partly by clinical
      heterogeneity, developmental differences in etiology (stronger genetic influences
      for depression symptom scores in adolescence than in childhood), and measurement
      issues, such as who rates the symptoms.

PMID- 16952766
TI  - Depression in infancy.
AB  - The evolution of the concept of depression in infancy (0-3 years) is relatively
      new and follows a path similar to the history of depression in adolescence, then
      in childhood, and in preschool years. It started with Spitz observation of a
      depressive clinical syndrome, named anaclitic depression, followed by Bowlby's
      description of three phases in the development of infants who have been separated
      from their caregiver. Kreisler linked life-threatening feeding disorders with
      depression in infancy. This article reviews the different causes of depression in
      infancy. Clinical vignettes illustrate some of them. The main unanswered question
      is whether depression in infancy can be primary. Diagnostic criteria,
      differential diagnoses and prognoses are reviewed, as well as therapeutic
      concerns specific to infancy.

PMID- 16952767
TI  - Preschool depression.
AB  - Within the past five years, significant strides have been made in the
      characterization of preschool (3-6 years of age) depression. Advances in this
      line of research have been made possible by increasing attention to the impact of
      developmental stage on symptom manifestation and the development of measures that
      appropriately assess for the presence of these developmentally specific symptoms.
      Available empirical evidence demonstrates that preschool depression is
      characterized by a specific and stable symptom constellation, associated
      impairment, biologic markers, and family history of similar disorders. This
      article reviews the relatively new body of evidence supporting the validity of
      preschool depression.

PMID- 16952768
TI  - Puberty and depression.
AB  - Unipolar depression only becomes more common in girls than boys after the age of
      13, as a result of an increased incidence of depressive episodes in girls at that
      time. This article reviews evidence that links multiple dimensions of maturation
      in the hypothalamo-pituitary-gonadal axis with this phenomenon. Effects of
      developmental status and timing have been implicated, but few studies have
      deployed either the measurement strategies or the statistical power needed to
      provide a satisfactory answer to the question regarding which components of
      puberty are most responsible.

PMID- 16952769
TI  - Cognitive behavioral therapy for depression in youth.
AB  - Without question, cognitive behavioral therapy (CBT) is the most studied non
      pharmacological intervention for the treatment of depression in youth, with over
      80% of published psychotherapy trials testing the effects of CBT protocols. Until
      quite recently, CBT also was widely proclaimed to be a highly effective
      intervention for youth depression, albeit with stronger data for adolescent than
      for child samples. However, within the past two years, a series of new findings
      have complicated this previously rosy picture of CBT. The most well-known results
      come from the Treatment of Adolescents with Depression Study (TADS, 2004). In the
      TADS investigation, CBT failed to outperform a pill placebo, while active
      medication treatments (fluoxetine alone and fluoxetine-plus-CBT) produced strong
      and consistent effects. In this article, the authors strive to make sense of
      these seemingly conflicting findings, provide direction for the appropriate use
      of CBT in practice given the current evidence base, and suggest areas of
      additional investigation that may help to clarify the current confusion on the
      effects of CBT.

PMID- 16952770
TI  - Interpersonal psychotherapy for depressed adolescents.
AB  - This article reviews interpersonal psychotherapy for depressed adolescents (IPT
      A). IPT-A is a time-limited, evidence-based psychotherapy for depressed,
      nonbipolar, nonpsychotic adolescents. The article focuses on goals and phases of
      IPT-A, identifies problem areas and core components of treatment, and discusses
      specific therapeutic techniques. Efficacy research and effectiveness studies of
      IPT-A are discussed. The limitations of the current knowledge and directions for
      future research are highlighted.

PMID- 16952771
TI  - Pharmacotherapy of child and adolescent depression.
AB  - Pediatric depression is a prevalent and recurrent condition that persists into
      adulthood and carries significant impairment, morbidity, and risk of mortality.
      Although there has been a surge of pediatric antidepressant studies in recent
      years, depression remains largely understudied, unrecognized, and untreated in
      children and adolescents. Few antidepressant trials have yielded positive results
      in pediatric depression. Regulatory agencies recently issued warnings against the
      use of selective serotonin reuptake inhibitors and newer antidepressants in
      depressed children and adolescents because of a possible link between their use
      and the appearance or worsening of suicidal ideation or attempts. The authors
      review data on efficacy and safety of antidepressants for the treatment of
      pediatric depression to provide treating clinicians with a basis on which to
      guide their treatment recommendations.

PMID- 16952772
TI  - Management of the depressed, suicidal child or adolescent.
AB  - Two prominent risk factors for completed suicide and suicidal behavior in
      adolescents are previous suicide attempts and a diagnosis of a depressive
      episode. Adolescents with different degrees of suicidal risk and severity are
      referred or admitted to various clinical settings. Research has yet to identify
      clearly the treatment of choice for suicidal patients. Regardless, clinical
      interventions should be based on a thorough suicide risk assessment. Treatment
      strategies should be multidimensional, targeting suicidal behavior and the
      underlying psychiatric illness or other personality and environmental risk
      factors. Because adolescents are referred from one clinical setting to another,
      continuity of care must be one of mental health practitioners' major concerns.
      Lack of continuity of care places patients at an elevated risk for additional
      suicide attempts.

PMID- 16952773
TI  - Treatment-resistant depression in adolescents: recognition and management.
AB  - Approximately 20% of adolescents experience at least one depressive episode by
      the time they enter their adult years. For most adolescents, depression, although
      serious, either remits spontaneously or responds to treatment. For a smaller but
      significant proportion of adolescents, however, depression can be long-lasting
      and relatively unresponsive to initial treatment. In this article the authors
      provide an operational definition of treatment-resistant depression, identify
      factors associated with treatment nonresponse, describe an approach to the
      management of treatment-resistant depression, and advance suggestions for
      promising avenues of research.

PMID- 16952774
TI  - Electroconvulsive therapy and transcranial magnetic stimulation: can they be
      considered valid modalities in the treatment of pediatric mood disorders?
AB  - Depression in children and adolescents is a severe and debilitating disorder and
      can be life-endangering. Even when it is not life-endangering, however, it has a
      grave impact on the quality of life of youngsters and their families, and
      interferes with normal growth and development. In recent years, the field of
      child psychiatry has become more aware of the limited applicability of data from
      the adult literature to children and adolescents and the limited resources that
      child psychiatrists have in treating depression. This awareness substantiates the
      need to define the place of electroconvulsive therapy and transcranial magnetic
      stimulation in the treatment of pediatric depression.

PMID- 16952775
TI  - Relapse and recurrence in pediatric depression.
AB  - Depression is a chronic illness in children and adolescents that often leads to
      long-term difficulties with recurrent episodes of depression. Standard treatment
      must continue beyond acute symptom reduction to a chronic disease management
      model, such as those used in pediatric asthma and diabetes. Within the chronic
      disease management model, treatment interventions are directed not only at the
      urgent or acute concern but also at the prevention of future problems. Lack of
      consistent efficacy in acute treatment studies has limited long-term prevention
      treatment research in pediatric depression. The impact of long-term treatments,
      both psychosocial and pharmacologic, is currently unknown.

PMID- 16952777
TI  - A music intervention to reduce anxiety before vascular angiography procedures.
AB  - Patients scheduled for vascular angiography are often anxious and frightened.
      High levels of anxiety may result in more difficult and painful procedures. Past
      research has reported mixed results for anxiety reduction techniques in other
      procedures settings, such as education, cognitive-behavioral skills, coping and
      relaxation skills, combinations of techniques, and music. Music as an
      intervention for pre-procedural anxiety prior to vascular angiography has not
      been studied. A randomized controlled trial of 170 patients was undertaken to
      determine whether 15 minutes of self-selected music reduced pre-procedure
      anxiety. The State Trait Anxiety Inventory was used to measure patients' anxiety.
      One-hundred sixty-six men and 4 women comprised the sample with an average age of
      66.8 years (SD 9.95, range 37 to 85 years). Patients who listened to music (n=89)
      reduced their anxiety score from 38.57 (SD 10.46) to 35.2 (SD 9.7), while those
      who did not listen to music (n=81) reduced their anxiety score from 36.23 (SD
      10.54) to 35.1 (SD 10.59); the difference between the groups was statistically
      significant (t=1.95, df 161, p=0.05). Pulse achieved a statistically significant
      reduction in the music group (t=2.45, df 167, p=0.02). Music is a noninvasive
      nursing intervention that patients enjoy and reduces their anxiety and their
      pulse rate. Further research should address using music to reduce anxiety in
      other interventional vascular angiography settings with equal numbers of men and
      women and comparing self-selected versus investigator-selected music.

PMID- 16952778
TI  - Endovascular repair of perirenal and Group IV thoracoabdominal aortic aneurysms:
      a case study report.
AB  - BACKGROUND: Endovascular aneurysm repair (EVAR) is an established technique used
      in infrarenal aneurysms. Fenestrated and branched endografts (FBEGs) are a new
      option for the treatment of perirenal and Group IV thoracoabdominal aortic
      aneurysms (TAAAs). With a case study design, the preparation, surgical technique,
      postoperative nursing care, and medical follow-up involved in Group IV TAAAs
      treated with an FBEG are discussed. METHODS: Detailed imaging with state-of-the
      art computed tomography scanning is used to create a custom-made endograft in
      which a combination of fenestrations, scallops, and covered or uncovered stents
      are used for the visceral arteries. This graft can be introduced in the arterial
      system through the femoral artery and delivered at the level of the perivisceral
      abdominal aorta. Perioperative nursing care in patients undergoing FBEG draws
      from protocols of an established EVAR program. With these protocols, preoperative
      assessment and education are completed to ensure that the patient is both
      physically and mentally prepared for the surgery. Intraoperatively, the nursing
      team is instrumental in the functioning of the case: The scrub nurse assists the
      surgeon while other registered nurses assist with invasive monitoring and
      emotional support for the conscious patient. Postoperatively, patients are taken
      directly from the recovery room to a step-down bed where close monitoring occurs.
      RESULTS: The use of FBEGs to treat Group IV TAAAs reduces the acuity of patient
      care by avoiding a thoracotomy and major surgical dissection, thus decreasing
      hospital length of stay. Although long-term follow-up remains limited, durability
      seems to be promising, and this procedure offers a viable option to high-risk
      patients. Because EVAR with FBEG is a new procedure in Canada, nurses involved
      with every aspect of care are challenged to maintain high levels of competency by
      continually educating themselves in this evolving field.

PMID- 16952779
TI  - Venous thromboembolism: scope of the problem and the nurse's role in risk
      assessment and prevention.
AB  - Deep vein thrombosis and pulmonary embolism, comprising different manifestations
      of the same clinical entity referred to as venous thromboembolism, are a
      significant cause of morbidity and mortality. Despite pulmonary embolism being
      considered the most preventable cause of in-hospital death, the use of
      appropriate thromboprophylaxis remains suboptimal in many patients. Nurses are on
      the frontline of thrombosis prevention. By playing an essential role in diagnosis
      and risk assessment, applying timely preventive methods, and providing vital
      educational and psychologic support for patients with venous thromboembolism,
      skilled nursing intervention can save lives.

PMID- 16952780
TI  - Deep venous thrombosis recommendations.

PMID- 16952781
TI  - The effect of xanthine oxidase inhibition upon ejection fraction in heart failure
      patients: La Plata Study.
AB  - BACKGROUND: Reactive oxygen species (ROS) have been linked to hypertrophy,
      remodeling and abnormal excitation-contraction coupling. Previous data
      demonstrated that an increase in oxidative stress is associated to the
      pathogenesis of congestive heart failure (CHF). We examined whether inhibition of
      the superoxide anion (*O2(-))-generating enzyme xanthine oxidase (XO) with
      oxypurinol may improve cardiac function in patients with CHF. METHODS AND
      RESULTS: A randomized, placebo-controlled, double-blind study on 60 patients
      (30/group) with New York Heart Association class II-III CHF, comparing 600-mg/day
      oxypurinol during 1 month with placebo, added to standard therapy. Effects on
      left ventricular ejection fraction (LVEF), serum uric acid (SUA) level, and 6
      minute walking test were analyzed. SUA decreased by 16.0 +/- 2.8 mg/L from
      baseline to Week 4 in the oxypurinol group relative to placebo (P < .01, n = 30
      per group). LVEF showed an increase of 4.7 +/- 2.6% from baseline to Week 4 in
      the oxypurinol group relative to placebo that did not reach statistical
      significance (P < .08). When patients with LVEF > 40% at baseline were excluded,
      a statistically significant increase of 6.8 +/- 2.8% from baseline to Week 4 was
      seen in the oxypurinol group relative to placebo (P < .02, n = 26 placebo, n = 21
      oxypurinol). No treatment-related adverse effects or increase in walking capacity
      were detected. CONCLUSION: Inhibition of XO by oxypurinol in patients with CHF
      decreases SUA and improves LVEF in patients with LVEF < or = 40% after 1 month of
      treatment.

PMID- 16952782
TI  - Effects of angiotensin-converting enzyme inhibitors in systolic heart failure
      patients with chronic kidney disease: a propensity score analysis.
AB  - BACKGROUND: Chronic kidney disease (CKD) is common in systolic heart failure
      (SHF) and is associated with poor outcomes. It is also associated with underuse
      of angiotensin-converting enzyme (ACE) inhibitors, yet the effect of these drugs
      in these (SHF-CKD) patients has not been well studied. The objective of this
      analysis was to determine if ACE inhibitor use was associated with reduction in
      mortality and hospitalization in SHF-CKD patients. METHODS AND RESULTS: Of the
      6800 SHF patients (ejection fraction < or = 45%) in the Digitalis Investigation
      Group trial, 1707 had CKD (serum creatinine 1.3-2.5 mg/dL for women and 1.5-2.5
      mg/dL for men). Propensity scores for ACE inhibitor use were calculated for each
      of the 1707 patients and were used to match 104 of the 127 no-ACE inhibitor
      patients with 104 ACE inhibitor patients. We estimated the effect of ACE
      inhibitor use on outcomes at 2 years using multivariable-adjusted Cox regression
      analyses. Overall, 35% of patients died and 67% were hospitalized. Compared with
      30% of ACE inhibitor patients, 39% of no-ACE inhibitor patients died (adjusted HR
      = 0.58; 95% CI = 0.35-0.96; P = .034). Compared with 64% of ACE inhibitor
      patients, 69% of no-ACE inhibitor patients had hospitalizations from all causes
      (adjusted HR = 0.69; 95% CI = 0.48-0.98; P = .040). CONCLUSION: We observed an
      association between use of ACE inhibitor and reductions in mortality and
      hospitalization in ambulatory chronic SHF patients with mild to moderate CKD.
      However, the results of this observational study should be interpreted with
      caution, and need to be replicated in larger and more recent databases, and
      confirmed prospectively in well-designed follow-up studies and/or randomized
      clinical trials.

PMID- 16952783
TI  - Nesiritide acutely increases pulmonary and systemic levels of nitric oxide in
      patients with pulmonary hypertension.
AB  - BACKGROUND: Pulmonary hypertension (PH) is characterized by decreased pulmonary
      vascular expression of nitric oxide (NOx), a vasodilator that increases levels of
      smooth muscle cyclic guanosine monophosphate (cGMP). This study investigated
      mechanisms by which the vasodilator B-type natriuretic peptide (BNP) affects the
      systemic and pulmonary vasculature in PH patients. METHODS AND RESULTS: Twenty PH
      patients with mean pulmonary artery (PA) pressure > 25 mm Hg were enrolled. Ten
      had precapillary (pulmonary capillary wedge pressure [PCWP] < or = 15 mm Hg) and
      10 had postcapillary (PCWP > 15 mm Hg) PH. Right heart catheterization was
      performed before and 30 minutes after intravenous nesiritide infusion. NOx and
      cGMP levels from the PA and systemic (AO) arteries were obtained before and after
      nesiritide infusion. The postcapillary PH patients demonstrated significantly
      reduced pulmonary vascular resistance after nesiritide; there was no change in
      the precapillary PH cohort. NOx levels increased significantly in both AO (P <
      .0001) and PA (P = .0093), as did cGMP levels (P < .0001). There was a higher
      increase in NOx levels from the pulmonary arteries in precapillary PH patients
      compared to postcapillary PH patients (P = .020). CONCLUSION: In PH patients,
      nesiritide infusion significantly increases NOx levels, suggesting a novel
      mechanism for its vasodilatory effects. These responses may differ between pre-
      and postcapillary PH patients.

PMID- 16952784
TI  - Plasma matrix metalloproteinase-9 level is correlated with left ventricular
      volumes and ejection fraction in patients with heart failure.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) can alter myocardial extracellular
      matrix and thereby contribute to adverse ventricular remodeling in progressive
      heart failure (HF). We hypothesized that increased plasma MMP levels correlate
      with increased left ventricular (LV) volumes and reduced LV ejection fraction
      (LVEF) in patients with HF. METHODS AND RESULTS: In the Randomized Evaluation of
      Strategies for Left Ventricular Dysfunction (RESOLVD) trial, patients with
      symptomatic HF and LVEF <0.40 were randomized to receive various combinations of
      therapies with candesartan, enalapril, and metoprolol CR. Left ventricular end
      diastolic volume (EDV), end-systolic volume (ESV), and LVEF were determined by
      radionuclide angiography at baseline and at Week 43. Baseline and Week 43 plasma
      MMP-2, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured
      by enzyme-linked immunosorbent assay in 184 patients in this substudy. At
      baseline, plasma MMP-9 correlated positively with ESV (Spearman's rank
      correlation coefficient rho = 0.17, P = .02) and negatively with LVEF (rho = 
      0.18, P = .01). After 43 weeks, LVEF, EDV, and ESV increased significantly (all P
      < .01); MMP-2 level increased (P = .01), but MMP-9 and TIMP-1 levels did not
      change significantly overall in the study population. Temporal changes in MMP-9
      level were inversely correlated with changes in LVEF (rho = -0.16, P = .04). In
      multivariable analysis adjusting for clinical characteristics and treatment, a
      smaller proportional change in MMP-9 level after 43 weeks (below versus above
      median) predicted a concurrent improvement in LVEF (odds ratio = 2.35, 95% CI
      1.24-4.46; P < .01). Similar relationships for MMP-2 and TIMP-1 were not
      observed. CONCLUSIONS: Elevated plasma MMP-9 levels correlated with lower LVEF
      and higher ESV, whereas increasing MMP-9 levels are associated with a concurrent
      deterioration of LV function. These findings suggest that monitoring of plasma
      markers of myocardial matrix remodeling may provide important prognostic
      information with respect to ongoing adverse LV remodeling in HF patients.

PMID- 16952786
TI  - Significance of 8-hydroxy-2'-deoxyguanosine levels in patients with idiopathic
      dilated cardiomyopathy.
AB  - BACKGROUND: Although oxidative stress mediated by reactive oxygen species plays
      an important role in the pathogenesis of heart failure (HF), good clinical
      markers for reactive oxygen species in patients with HF have not been
      established. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is formed from deoxyguanosine
      in DNA by hydroxyl free radicals and might serve as a sensitive biomarker of
      intracellular oxidative stress in vivo. Thioredoxin (TRX) is known to be induced
      in cells as a radical scavenger against oxidative stress. The aim of this study
      is to evaluate the clinical significance of the serum 8-OHdG and TRX of patients
      with chronic HF with idiopathic dilated cardiomyopathy (DCM). METHODS AND
      RESULTS: We estimated serum 8-OHdG and TRX levels using enzyme-linked
      immunosorbent assay in 32 patients with DCM and investigated the impact of these
      markers to the clinical characteristics of these patients. Serum levels of 8
      OHdG, but not TRX were significantly correlated with New York Heart Association
      functional class, left atrial diameters, left ventricular end-diastolic
      diameters, left ventricular end-systolic diameters, and plasma levels of brain
      natriuretic peptide. CONCLUSION: These data suggest oxidative DNA damage is
      increased in patients with DCM according to the severity of HF. Serum levels of 8
      OHdG may represent clinically useful markers of left ventricular remodeling.

PMID- 16952785
TI  - Early activation of an altered thyroid hormone profile in asymptomatic or mildly
      symptomatic idiopathic left ventricular dysfunction.
AB  - BACKGROUND: Although an altered thyroid metabolism has been documented in
      patients with overt heart failure, no evaluation has been made of a heart-thyroid
      interaction in mildly symptomatic patients with idiopathic left ventricular
      dysfunction (ILVD). We wanted to assess the thyroid state in patients with ILVD.
      METHODS AND RESULTS: Eighty-six patients (age 60 +/- 10 years) were enrolled into
      the study. Thyroxine (T4), triiodothyronine (T3), thyrotropin, brain and atrial
      natriuretic peptides (BNP, ANP), noradrenaline, aldosterone, renin activity, and
      interleukin-6 were measured. Patients were divided into three groups: Group N
      with LV ejection fraction (EF) > or = 50% (n = 28), Group I with LVEF > 35%-< 50%
      (n = 34), Group II with LVEF < or = 35% (n = 24). There was a significant
      correlation between T3 and LVEF (r = 0.25, P = .02) and a negative correlation
      between T3 and BNP (r = -0.37, P < .0001). At univariate analysis T3 was a
      predictor of LV dysfunction, whereas BNP was the most important predictor at
      multivariate analysis (P = .002). T3 was the only predictor of New York Heart
      Association class at multivariate analysis. CONCLUSION: An altered thyroid
      profile characterized by a reduction in peripheral production of biologically
      active T3 is related to LV dysfunction and early symptoms of heart failure in
      patients with ILVD.

PMID- 16952787
TI  - Anemia, physical disability, and survival in older patients with heart failure.
AB  - BACKGROUND: Anemia is common in congestive heart failure, and it has been
      associated with poor prognosis. The effect of anemia on functional ability in
      heart failure has not been described. We evaluated the relationship of anemia,
      physical disability, and survival in patients with heart failure. METHODS AND
      RESULTS: One-year longitudinal study of 567 non-disabled, hospitalized heart
      failure patients, age > or = 65 years, enrolled in the Italian Group of
      Pharmacoepidemiology in the Elderly Study. Anemia was defined according to the
      World Health Organization criteria. Physical disability was defined as dependence
      in performing at least 2 basic activities of daily living. After adjustment for
      disease severity and health-related variables, anemia was associated with higher
      risk of disability (odds ratio = 2.17; 95% confidence interval [CI] = 1.12-4.24).
      After stratification according to gender, a strong relationship of anemia and
      risk of disability persisted in women, but it was reduced in men. Anemic women
      were significantly more likely to die during the follow-up, even after adjustment
      for potential confounders (hazard ratio = 2.33; CI = 1.02-5.30). CONCLUSION:
      Anemia is a predictor of physical disability in older heart failure patients, and
      in women anemia is associated with increased mortality.

PMID- 16952788
TI  - Socioeconomic factors as predictors of incident heart failure.
AB  - BACKGROUND: Studies of socioeconomic factors as predictors of heart failure (HF)
      are few and have given opposing results. Further, it is unknown if these factors
      predict incident HF independently of myocardial infarction and other established
      risk factors for HF. METHODS AND RESULTS: In a community-based cohort of 2314
      middle-age men free from HF, valvular disease, and previous myocardial infarction
      at baseline, socioeconomic factors were examined as predictors for HF using Cox
      proportional hazards analyses. In multivariable Cox proportional hazards models
      adjusted for established risk factors for HF (hypertension, diabetes,
      electrocardiographic left ventricular hypertrophy, smoking, serum cholesterol,
      and interim myocardial infarction), low occupational classification (hazard ratio
      [HR] 1.55, 95% confidence interval [CI] 1.03-2.35 for low vs. high occupational
      classification), low education level (HR 1.98, 95% CI 1.07-3.68 for elementary
      school vs. college exam) and being unmarried (HR 1.44, 95% CI 0.99-2.10 for being
      unmarried vs. being married) increased the risk of HF. CONCLUSION: High
      occupational classification and high education level decreased, and being
      unmarried increased, the risk of subsequent HF in middle-age men, via mechanisms
      largely independent of established risk factors for HF, including an interim
      myocardial infarction. Further studies are needed to understand the mechanisms
      behind these associations.

PMID- 16952789
TI  - Congestive heart failure patients report conflict with their physicians.
AB  - BACKGROUND: Given the importance of the doctor-patient relationship, we examined
      the prevalence and nature of patients' perceived conflicts with the physicians
      caring for their congestive heart failure (CHF). METHODS AND RESULTS: This cross
      sectional study recruited patients with CHF in the outpatient and inpatient
      service of a tertiary referral hospital. Patients completed demographics,
      semistructured interviews, and surveys of emotional and health status. CHF
      physiologic measures and comorbidities were abstracted from the medical record. A
      team of 2 blinded coders analyzed the interviews. Thirty-one percent of the 289
      patients reported difficulties with physicians. In the bivariate analysis, only
      marital status was significantly associated with conflict. Major problems
      included the providers' poor communication skills (20%), trust in the physicians'
      competence (18%), and insufficient medical information (16%). Patients identified
      care outside the tertiary referral hospital (13%) and inadequate communication
      between physicians (9%) as additional sources of difficulty. CONCLUSION:
      Perceived conflict with providers is common in patients with CHF. Patient-level
      factors, however, did not predict conflict, which differs from our previous
      findings with hepatitis C patients. Perceived conflict is troubling because it
      can undermine the trust in the doctor-patient relationship, thereby weakening the
      therapeutic bond necessary to care for this sick and often vulnerable population.

PMID- 16952790
TI  - A systematic meta-analysis of the efficacy and heterogeneity of disease
      management programs in congestive heart failure.
AB  - BACKGROUND: We sought to systematically combine the evidence on efficacy of
      disease management programs (DMPs) in the treatment of congestive heart failure
      (CHF), to identify and explain heterogeneity of results from prior studies of
      DMPs, and to assess potential publication bias from these studies. METHODS AND
      RESULTS: We conducted a systematic literature search on randomized clinical
      trials investigating the effect of DMPs on CHF outcomes and performed meta
      analyses and meta-regressions comparing DMPs and standard care for mortality and
      rehospitalization. We included 36 studies from 13 different countries (with data
      from 8341 patients). Our meta-analysis yielded a pooled risk difference of 3%
      (95% confidence interval [CI] 1-6%, P < .01) for mortality and of 8% (95% CI 5
      11%, P < .0001) for rehospitalization, both favoring DMP. Factors explaining
      heterogeneity between studies included severity of disease, proportion of beta
      blocker at baseline, country, duration of follow-up, and mode of postdischarge
      contact. No statistically significant publication bias was detected. CONCLUSION:
      DMPs have the potential to reduce morbidity and mortality for patients with CHF.
      The benefit of the intervention depends on age, severity of disease, guideline
      based treatment at baseline, and DMP modalities. Future studies should directly
      compare the effect of different aspects of disease management programs for
      different populations.

PMID- 16952791
TI  - Noninvasive calibration of cardiac pressure transducers in patients with heart
      failure: an aid to implantable hemodynamic monitoring and therapeutic guidance.
AB  - BACKGROUND: Implantable cardiac pressure monitors require assurance of
      calibration. This study evaluated if airway pressure responses during Valsalva
      maneuver (VM) can be used for calibrating intracardiac pressure transducers.
      METHODS AND RESULTS: Thirty-eight heart failure patients performed VMs while
      cardiac and airway pressures were recorded. Patients were designated as Lower (L)
      if baseline PCW was <20 mm Hg (n = 17); otherwise, they were categorized as
      Higher (H) (n = 21). VMs were repeated in 9 H patients after nitroglycerin.
      Procedural success was 92% and there were no complications. Differences between
      filling pressure and airway pressure (effective pressure) were eliminated during
      VM (RA(eff) = -0.9 +/- 1.3, RVED(eff) = 1.2 +/- 1.1, PCW(eff) = 2.1 +/- 2.8, and
      LVED(eff) = 0.9 +/- 1.6 mm Hg), and filling pressures were highly correlated with
      airway pressure r = 0.94. On average, group H had higher PCW(eff) and LVED(eff)
      than L patients by 1.8 and 2.5 mm Hg (P < or = .002), respectively, but after
      nitrates their responses were identical. CONCLUSION: The relationships between
      cardiac filling pressure and airway pressure during the Valsalva maneuver are
      sufficiently reliable to be considered as a new, noninvasive method for
      establishing the calibration of cardiac pressure sensors in patients with heart
      failure.

PMID- 16952792
TI  - Preserved norepinephrine reuptake but reduced sympathetic nerve endings in
      hypertrophic volume-overloaded rat hearts.
AB  - BACKGROUND: In congestive heart failure (CHF), an activation of the cardiac
      sympathetic nervous system results in depleted cardiac norepinephrine (NE)
      stores. The underlying regulatory mechanisms are discussed controversially and
      were investigated in the present study in CHF resulting from volume overload.
      METHODS AND RESULTS: Aorto-caval shunt (AVS) was performed in rats. Plasma NE
      levels were determined by radioenzymatic assay, left ventricular NE by high
      performance liquid chromatography, endothelin-1 by enzyme-linked immunosorbent
      assay. Tyrosine-hydroxylase (TH)- and nerve growth factor (NGF)-mRNA was
      determined by Northern blot analysis and ribonuclease-assay. Cardiac [3H]-NE
      uptake was measured in isolated perfused hearts. Glyoxylic acid-induced
      histofluorescence was used to quantify cardiac sympathetic nerves. Compared with
      sham-operated animals (SH), AVS rats were characterized by depleted cardiac NE
      stores and enhanced NE plasma levels. Neither TH-mRNA levels in stellate ganglia,
      nor cardiac [3H]-NE-uptake were reduced in AVS. The left ventricular density of
      sympathetic nerves was markedly decreased. Gene expression of myocardial NGF (a
      positive regulator of NE reuptake and cardiac sympathetic nerve density) and left
      ventricular endothelin-1 (a negative regulator of NE reuptake and positive
      regulator of cardiac NGF expression) were unchanged. CONCLUSION: In volume
      overloaded hypertrophic hearts, depletion of cardiac NE stores is caused by a
      reduction of the sympathetic nerve density, whereas cardiac NE reuptake is
      preserved.

PMID- 16952793
TI  - Alagebrium: benefit on peripheral arteries.

PMID- 16952794
TI  - Diversity in management of heart failure patients.

PMID- 16952797
TI  - Application of the acute respiratory distress syndrome network low-tidal volume
      strategy to pediatric acute lung injury.
AB  - In summary, most of the available data suggest that pediatric patients should be
      ventilated with low tidal volumes. The 6-mL/kg IBW tidal volume strategy as used
      in the ARDSNet studies is a reasonable target, having since been rigorously
      tested in several large, clinical trials (adult and pediatric). The mortality
      associated with ALI in these studies has never been lower, certainly supporting
      continued use of the 6 mL/kg target tidal volume as the "gold standard" and,
      thus, eliminating any equipoise in designing a pediatric trial comparing 6 mL/kg
      to a larger tidal volume. With mortality rates in children from ALI nearing 8% to
      22% and with no clear surrogate outcomes identified to date, the sample sizes
      needed to show a significant clinical effect would be prohibitively large.
      Nonetheless, future research should compare 6 mL/kg IBW to even smaller tidal
      volumes or to high frequency ventilation in an attempt to further reduce the
      mortality associated with ALI and ARDS in the pediatric population.

PMID- 16952798
TI  - Is permissive hypoxemia a beneficial strategy for pediatric acute lung injury?
AB  - The adverse effects of high oxygen levels have been widely reported, and
      clinicians have struggled for many years to find the ideal balance between
      inspired oxygen levels and acceptable arterial oxygen saturation. However, when
      asked "what is an acceptable oxygen saturation," one is hard pressed to find a
      definitive answer. Permissive hypoxemia is a concept similar to the well
      described strategy of permissive hypercapnia. It is a strategy that allows the
      arterial oxygen saturation to be less than normal in an attempt to minimize the
      amount of artificial support provided to the lungs by mechanical ventilation. It
      must be noted that this concept is predominantly based on physiology, as data in
      the medical literature are very limited. Permissive hypoxemia as an approach to
      acute lung injury remains controversial in the clinical setting.

PMID- 16952799
TI  - Is permissive hypercapnia a beneficial strategy for pediatric acute lung injury?
AB  - It is clear that mechanical ventilation strategies influence the course of lung
      disease, and the choice of a ventilation strategy that avoids volutrauma and
      atelectrauma is firmly based on experimental literature and clinical experience.
      The application of a lung-protective strategy with reduced tidal volumes,
      effective lung recruitment, adequate PEEP to minimize alveolar collapse during
      expiration, and permissive hypercapnia has been shown to be advantageous in adult
      patients who have ARDS, although it has not been systematically studied in
      children. A significant body of literature confirms the beneficial effects of
      hypercapnic acidemia in the setting of acute lung injury. As a corollary,
      experimental evidence indicates that buffering hypercapnic acidosis abrogates its
      protective effects. The use of permissive hypercapnia as part of a lung
      protective strategy in children should be accepted and perhaps even desired,
      provided it does not result in significant hemodynamic instability. This
      acceptance should be tempered with the recognition that a low-stretch, reduced
      tidal volume strategy without hypercapnia has also been shown to improve outcomes
      in adults who have ARDS and that HFOV can generally provide lung-protective
      ventilation without necessarily inducing hypercapnia. Thus, a synthesis of the
      available clinical and research data strongly supports a graded approach to
      managing patients who have acute lung injury requiring intubation. The highest
      priority should be a mechanical ventilation strategy that limits the tidal
      volume, with the allowance of hypercapnia to a degree that does not compromise
      hemodynamic status.

PMID- 16952800
TI  - Ventilator management protocols in pediatrics.
AB  - Management of mechanical ventilation is a complex process with outcomes affected
      by multiple patient and caregiver variable. Well-constructed protocols represent
      the synthesis of best available evidence regarding ventilator management. In
      adults, protocols improve important outcomes such as duration of mechanical
      ventilation, length of stay, and complication rates; however, protocols are not
      uniformly successful. In pediatrics, the available evidence does not suggest that
      ventilator management protocols should be adopted routinely, which may be due to
      pediatric-specific attributes such as a generally shorter weaning duration.
      Evidence suggests support for protocols to carefully titrate sedation. In
      addition, daily assessment of SBTs improves patient outcomes and should be more
      uniformly adopted in pediatrics. Ventilator-related outcomes may be affected by
      other confounding factors such as nutrition and fluid balance. Specific
      subpopulations, such as children who have congenital heart disease, may present
      opportunities for focused use of ventilator management protocols. Protocolized
      ventilation has an important place in trials of new therapeutic strategies such
      as surfactant or proning. It is hoped that future research will further define
      the appropriate use of protocols in the general PICU population. Although
      specific protocols cannot be routinely recommended, a multidisciplinary team
      approach to synthesizing available literature and determining best practice is a
      useful model. This approach will foster "team ownership" of ventilator management
      by all involved, thus engendering the best possible outcomes for critically ill
      children who require mechanical ventilation.

PMID- 16952801
TI  - To stop or not to stop: how much support should be provided to mechanically
      ventilated pediatric bone marrow and stem cell transplant patients?
AB  - Every publication to date reporting the outcome of intensive care support for
      pediatric SCT patients must be viewed with caution because all are single
      institution, retrospective reports. Nevertheless, some of the conclusions made by
      these investigators appear to be clinically relevant. First, an SCT patient who
      requires intensive care support does not automatically have a dismal chance of
      survival. Survival rates in recent reports range from 15% to 36%, which is
      reasonable when the overall post-transplant survival rate for non-ICU patients
      may be only 50%. Second, adverse risk factors differ from center to center,
      likely due to the wide variation in patient populations, donor source, and
      transplant preparation regimens. Third, MSOF is a consistent adverse risk factor
      for survival. An additional conclusion that can be drawn from the data presented
      in this article is that patients who do not show significant, objective
      improvement by the second week of PICU care are unlikely to survive. The
      limitation or withdrawal of life-sustaining medical support should be recommended
      to the patient, the patient's family, and the patient's doctors. Although there
      are no predictive models that are 100% reliable for these clinical situations, in
      the author's experience, most families and physicians view critical care support
      beyond 2 weeks, in the absence of clinical improvement, as futile care. It is
      clear that better data are needed in the form of prospective, multi-institutional
      studies that include the therapeutic efficacy of interventions such as high
      frequency oscillatory ventilation, continuous venovenous hemodialysis, early use
      of noninvasive ventilation (ie, noninvasive positive pressure ventilation), the
      use of biologic agents to decrease inflammation, the impact of new antifungal
      medications, and lung-protective ventilation with permissive hypercapnia. Of
      these potential therapies, the author is aware of only one multi-institutional
      study involving continuous venovenous hemodialysis at this time.

PMID- 16952802
TI  - The role of noninvasive ventilation for acute respiratory failure.
AB  - The use of NIV has been shown to facilitate discontinuing ventilatory dependence
      as well as provide support for adult patients with chronic lung disease without
      the need for endotracheal intubation. In fact, NIV has recently described as a
      potential support strategy following extubation failure. Therefore, using NIV as
      a bridge to liberation from mechanical ventilation may decrease many of the
      complications associated with long-term use of invasive airway devices as well
      complications from reinsertion of an artificial airway. Although firm data
      supporting the use of NIV in the adult population exists, the use of NIV in the
      pediatric population is based primarily on a series of case studies,
      retrospective chart reviews, and extrapolation from the adult data. The use of
      NIV for infants and children remains controversial. The important question to be
      asked is why there is a lack of randomized controlled trials on NIV in
      pediatrics? The answer lies somewhere between the lack of equipment designed
      specifically for pediatrics and the smaller number of patients available compared
      with adults. Data from the adult population may be more readily adapted to older
      children; however, it remains difficult to determine the criteria for noninvasive
      ventilatory use in infants and young children. In fact, this lack of data makes
      the formulation of firm selection guidelines for infants and children essentially
      impossible. However, for a select groups of pediatric patients with acute
      respiratory failure for whom an appropriate noninvasive device with interface is
      available, a trial of NIV may be seem reasonable to avoid the known negative
      effects of intubation and invasive mechanical ventilation.

PMID- 16952803
TI  - Is high-frequency ventilation more beneficial than low-tidal volume conventional
      ventilation?
AB  - The ventilator goals of the ICU clinician faced with caring for a critically ill
      child who has ALI/ARDS remain relatively simple: provide adequate ventilation and
      oxygenation without overdistending alveoli or furthering lung injury. How one
      obtains these goals is much less simple. The current use of CV calls for the use
      of relatively low V(T)s and limiting peak inspiratory pressure and plateau
      pressure while accepting a certain degree of respiratory acidosis. The ICU team
      can also often achieve these same goals with HFOV. How, then, does one use
      evidenced-based medicine to pick the best mode of mechanical ventilation for a
      particular patient? The answer is controversial, to say the least. Does one start
      with a gentle, open-lung mode of CV then switch to HFOV if the child
      deteriorates? Or does one use HFOV from the very early stages of ALI? Animal data
      appear to point to advantages of HFOV when used early in the course of ALI. Most
      of these studies report a beneficial effect of HFOV when applied on expanded
      lungs in the early stages of the disease process. These beneficial effects
      encompass improved gas exchange, oxygenation, lung tissue morphology and
      pulmonary mechanics. The studies by Arnold and colleagues in the pediatric
      population also help to answer our questions. In their work, the early initiation
      of HFOV was associated with improved gas exchange and a trend toward a lower
      mortality. In adults, Derdak and colleagues demonstrated the superiority of HFOV
      in terms of gas exchange and oxygenation; however, no statistical significant
      difference was found for mortality. So, where is the clinician left after a
      review of these data? It would appear that (1) low-V(T) CV remains a cornerstone
      of therapy for the pediatric patient who has ALI/ARDS; (2) HFOV is a safe and
      well-tolerated mode of mechanical ventilation; (3) early use of HFOV (as opposed
      to the rescue use of this mode) may be of benefit based on animal and human data;
      and (4) like so many areas of pediatric critical care, clinicians must await new
      data and trials that will help them continue to improve the care they provide.

PMID- 16952804
TI  - High-frequency jet and oscillatory ventilation for neonates: which strategy and
      when?
AB  - Both HFOV and HFJV are important adjuncts to the ventilatory care of sick infants
      and children. Today, it is important that neonatologists, pediatric intensivists,
      and respiratory care practitioners understand these ventilators and the options
      they provide. It is no longer necessary to continue the use of damaging pressures
      and volumes with CV simply because no other option is available. The clinician
      who understands not only the pathology and physiology of the underlying lung
      condition but also understands the available choices in ventilators, how each
      ventilator functions, and what potential advantage it may offer his patients is
      able to provide the best possible care to these critically ill patients.

PMID- 16952805
TI  - Extubation criteria in infants and children.
AB  - Predictors of extubation outcome attempt to provide objective data that may help
      to modify clinical decision making at the bedside. This article reviews the
      subjective and objective extubation readiness predictors tested in the pediatric
      medical literature. An understanding of the predictive capacity of the extubation
      criteria is vital for the critical care physician. No test is likely to predict
      the extubation outcome for an individual patient with absolute certainly.
      Therefore, weaning and extubation practices in the pediatric critical care
      setting remain variable, and teh development of standardized protocols for
      extubation remains controversial. Perhaps future well-designed, large-scale
      trials will provide more accurate predictors of extubation readiness to guide the
      safe and timely extubation of the pediatric patient.

PMID- 16952806
TI  - What is the role of airway pressure release ventilation in the management of
      acute lung injury?
AB  - The lack of published evidence supporting the use of APRV in the pediatric
      critical care patient population may diminish its effective application in
      respiratory failure. The effect of APRV on the number of ventilator days, ICU
      stay, and mortality still remains to be studied. Further application of APRV in
      the role of rest settings for ECMO especially in the pediatric cardiac patient
      population needs to be investigated. Will the use of APRV decrease the time for
      adequate lung recruitment, decrease sheer trauma, and/or promote earlier
      decannulation upon the restoration of tolerable cardiac function? Can APRV be
      utilized as a re-recruitment maneuver? A comparison of APRV over sustained in a
      randomized-controlled fashion, will there be a significant difference in
      ventilator days, length of ICU stay, and/or mortality? Does re-recruitment at
      plateau pressures during suctioning, patient position changes, or in the face of
      increased airway resistance decrease the number of ventilator days, length of ICU
      stay, and/or mortality? Does the use of continuous monitoring of carbon dioxide
      production aid in optimizing P(high)? The list of questions, both speculative and
      scientific are too numerous to list. Speculation leads to inquiry which over time
      drives science. More focus is needed on randomized, controlled trials. Initially
      the comparison of APRV to HFOV needs to be the primary focus for a proactive
      approach for ALI. Once a comfort level is established with this modality, further
      scientific inquires will follow. In the meantime, its use is likely to remain
      controversial.

PMID- 16952807
TI  - The role of inhaled nitric oxide and heliox in the management of acute
      respiratory failure.
AB  - The application of positive-pressure mechanical ventilation is one of the
      cornerstones of support for patients with acute respiratory failure.
      Unfortunately, the clinical condition of some patients does not improve, despite
      escalating ventilatory support. Adjunctive therapies to mechanical ventilation
      such as nitric oxide and heliox have been explored for the purposes of minimizing
      injurious settings and supporting adequate gas exchange. As specific therapies
      continue to evolve, clinicians should have a clear understanding of the
      physiologic basis and evidence before deciding to use any adjunctive therapy.
      This article discusses the role of nitric oxide and heliox as adjunct therapies
      to mechanical ventilation. Many questions remain about the role of these unique
      gases in the management of pediatric patients with acute respiratory failure.
      Should nitric oxide be used outside of its approved indication, and should heliox
      be used at all due to the lack of definitive evidence?

PMID- 16952808
TI  - Do all mechanically ventilated pediatric patients require continuous capnography?
AB  - With most patients in modern ICUs requiring mechanical ventilation, any
      technology that may lead to more optimal ventilatory strategies would be
      invaluable in the management of critically ill patients. The focus of most
      ventilator strategies is protecting the lung from the deleterious effects of
      mechanical ventilation. Every effort is made to minimize the duration of
      mechanical ventilation while optimizing the potential for successful extubation.
      A concise organized plan based on objective criteria that is adjusted to meet
      changes in patient status is clearly recommended. Continuous capnographic
      monitoring provides clinicians with clear, precise, objective data that may prove
      beneficial in the design and implementation of mechanical ventilatory strategies.
      There are no clear-cut methods for achieving the optimal ventilator strategy for
      a specific patient. Although guidelines and management theories exist throughout
      the medical literature, in practice, they often merely serve as loose guidelines.
      The dynamic properties of an acutely ill patient make the management of
      mechanical ventilation an ongoing process requiring clinical assessment and
      planning by multidisciplinary members of the patient care team. Comprehensive
      evaluation of ventilatory management strategies and patient responses must be
      made by a collaborative effort of physicians, respiratory care practitioners, and
      nurses. An objective, consistent approach to the overall management is essential.
      Although still controversial, it is the authors' opinion that volumetric
      capnograph provides the data necessary to establish adequate gas delivery,
      optimal PEEP, and effective ventilation with the least amount of mechanical
      assistance, regardless of clinician or institutional preferences.

PMID- 16952809
TI  - Is there any need for expanding the perineural space before catheter placement in
      continuous femoral nerve blocks?
AB  - BACKGROUND AND OBJECTIVE: There is debate regarding the benefit of perineural
      space expansion before catheter placement in continuous femoral nerve block. This
      question is addressed in this prospective, comparative, and randomized study.
      METHODS: Sixty patients scheduled for total knee replacement were randomly
      assigned to receive continuous femoral nerve block with or without perineural
      space expansion using 10 mL dextrose 5% in water (D5W) flush before stimulation
      guided catheter placement. Femoral block was initiated with a 5-mL bolus followed
      by an infusion of 5 mL/h ropivacaine 0.2% during the 2-hour surgery. The number
      of attempts before successful placement of the stimulating catheter and the
      resistance during its insertion were assessed. Patients also received obturator
      nerve blocks by using ropivacaine 0.75% (10 mL) and sciatic nerve blocks (20 mL).
      The number of boluses of ropivacaine 0.2% needed to achieve zero VAS scoring was
      recorded in the postanesthesia care unit during the 2-hour stay. Images of the
      contrast spread were also studied. RESULTS: There were 30 patients in each group.
      The number of successful catheter placements at the first attempt was higher with
      expansion than without (22 vs. 8, P = .007). The resistance felt during insertion
      was lower with than without expansion (P = .01). More boluses of ropivacaine were
      required postoperatively without expansion (P = .03). No difference between
      groups was found regarding the images of the contrast spread. CONCLUSION:
      Expansion of the perineural space with D5W is useful for catheter placement in
      continuous femoral nerve block.

PMID- 16952810
TI  - Local anesthetics in lipid-depot formulations--neurotoxicity in relation to
      duration of effect in a rat model.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the possible
      local neurotoxicity of a number of lipid-depot formulations of local anesthetics
      in relation to their duration of action in sciatic-nerve block. METHODS:
      Formulations that contain 2%, 4%, 8%, 16%, 32%, or 64% of a mixture of
      bupivacaine and lidocaine base 4:1 in medium-chain triglyceride were prepared and
      evaluated, together with 0.5%, 1.0%, and 2.0% bupivacaine HCl solutions,
      bupivacaine 4.2% or 7.0% in medium-chain triglyceride, and 20% lidocaine base in
      a polar lipid vehicle. The duration of sensory and motor sciatic-nerve block was
      determined in rats. A week later, the sciatic nerves were dissected and removed
      for histopathologic examination by light microscopy. RESULTS: The duration of
      sensory and motor-nerve block was prolonged almost 4 times with the 32% and 13
      times with the 64% bupivacaine:lidocaine formulation, in comparison to the 0.5%
      aqueous solution. The 64% formulation was applied by injection and also placed
      directly on the nerve with similar results. Slight to moderate signs of
      neurotoxicity were only found after administration of the 64% formulation.
      CONCLUSIONS: The findings suggest that depot formulations of local anesthetics
      with advantageous pharmaceutical and pharmacologic properties can be prepared by
      use of bupivacaine as the active component and natural lipids as carriers. A
      favorable balance between effects and toxicity may conceivably be obtained. After
      supplemental testing in more sensitive models for toxicity, such formulations
      could be candidates for clinical trials.

PMID- 16952811
TI  - Fluoroscopically guided epidural block in the thoracic and lumbar regions.
AB  - BACKGROUND AND OBJECTIVES: Epidural block in the midthoracic region is difficult,
      even with fluoroscopically guided methods, because of the inability to view the
      interlaminar space on radiographs. We have, therefore, proposed fluoroscopically
      guided epidural block for the midthoracic region, as well as other thoracic and
      lumbar regions, by use of the pedicle as a landmark to show the height of the
      interlaminar space. METHODS: Twenty patients scheduled to receive an indwelling
      epidural catheter at Th6-7, Th9-10, Th12-L1, or L3-4 were studied. The skin
      insertion site was at the junction of a line parallel to the vertebral column
      that passed through the middle of the pedicle and the lower border of vertebral
      body, immediately inferior to the target interlaminar space on an anteroposterior
      radiograph. The needle was walked up the lamina, and the interlaminar space was
      sought near the midline of the vertebra at the height of the pedicle. RESULTS:
      Epidural block was easily performed in all cases. No difference was observed in
      the angulation of the epidural needle among the groups; the mean inward and
      upward angulation were 38 degrees and 63 degrees , respectively, although the
      skin insertion site relative to the spinous process was different among the
      groups. CONCLUSIONS: This study showed the usefulness of our fluoroscopically
      guided method for the midthoracic region, and other thoracic and lumbar regions.
      We propose an alternative method for a blind epidural approach at Th6-7, Th9-10,
      Th12-L1, or L3-4.

PMID- 16952812
TI  - Combined lumbar-plexus and sciatic-nerve blocks: an analysis of plasma
      ropivacaine concentrations.
AB  - BACKGROUND AND OBJECTIVES: Lumbar-plexus and sciatic-nerve blocks are commonly
      combined for lower-extremity anesthesia using large doses of ropivacaine. Limited
      information is available about the pharmacokinetics of this practice. We analyzed
      plasma ropivacaine concentrations after single-injection lumbar-plexus blocks
      with and without sciatic-nerve blocks. METHODS: Twenty patients having lower
      extremity surgery using a lumbar-plexus block with 0.5% ropivacaine with
      1:400,000 epinephrine (35 mL, n = 10) or the same lumbar-plexus block with the
      addition of a sciatic-nerve block (25 mL, n = 10, 60 mL total) using the same
      solution were enrolled. Venous blood samples were collected at 5, 15, 30, 45, 60,
      120, and 240 minutes after block placement and analyzed for total ropivacaine
      concentration by use of gas chromatography. Individual timepoints, maximum
      concentrations (C(max)), and time to C(max) (T(max)) were compared. Values are
      mean +/- SD. RESULTS: Both groups demonstrated a rapid increase in plasma
      concentration over the first 30 to 45 minutes. Concentrations were greater for
      those who received both blocks (P = .0005) at all timepoints. The lumbar-plexus
      block C(max) was less (986 +/- 221 ng/mL) than for the combined blocks (1,560 +/-
      351 ng/mL, P = .0004). The T(max) was greater for the lumbar plexus (80 +/- 49
      min) than for the combined blocks (38 +/- 22 min, P = .03). There was no
      relationship between the C(max) and patient age, weight, or body mass index.
      CONCLUSIONS: The results of this study demonstrate that the plasma ropivacaine
      concentrations increase quicker when a sciatic-nerve block is added to a lumbar
      plexus block, but C(max) remains below the toxicity threshold.

PMID- 16952813
TI  - Health-related quality of life in sacroiliac syndrome: a comparison to
      lumbosacral radiculopathy.
AB  - BACKGROUND AND OBJECTIVES: This study attempts to assess the intensity and
      quality of pain and health-related quality of life in patients with sacroiliac
      syndrome and to compare those constructs to patients with lumbar radiculopathy.
      METHODS: A retrospective review of patient records with the diagnosis of
      sacroiliac syndrome or lumbar radiculopathy was performed. Patients with
      sacroiliac syndrome were age and gender matched to patients with lumbar
      radiculopathy. Data from the McGill Pain Questionnaire, visual numerical pain
      scores, and SF-36 health-related quality of life measure (version 2) were
      compared between groups. RESULTS: The age of patients with a traumatic etiology
      for sacroiliac syndrome was lower than those with previous back surgery and
      "idiopathic" etiologies (P < .02). Duration of pain in patients with "idiopathic"
      etiology was longer in comparison to those with previous back surgery (P < .005).
      No statistical difference occurred between patients with sacroiliac syndrome and
      lumbar radiculopathy with respect to McGill pain scores, visual numerical pain
      scores, and SF-36 health-related quality of life measure. CONCLUSIONS: The
      results of this study suggest the following: (1) no true difference exists in the
      health-related quality of life or pain scores/descriptors between patients with
      SI syndrome or lumbar radiculopathy, or (2) the presence of comorbid spinal
      conditions confounds the ability of the SF-36 to detect disparities in health
      related quality of life among differing etiologies of low-back pain, despite the
      use of rigorous diagnostic criteria, and/or (3) other factors besides the
      diagnostic categories of low-back pain (e.g., functional capability,
      psychological stress) may be primary determinants of health-related quality of
      life. To our knowledge, no other study has attempted to use the SF-36 to detect
      differences in health-related quality of life among patients with different
      spinal diagnoses.

PMID- 16952814
TI  - Effect of preoperative epidural morphine administration on desflurane
      requirements during gynecologic surgery.
AB  - BACKGROUND AND OBJECTIVES: The goal of this study is to examine the influence of
      epidural morphine on the end-tidal desflurane concentration titrated to maintain
      the bispectal index (BIS) values between 40 and 60 during gynecologic surgery.
      METHODS: Forty patients undergoing transabdominal hysterectomy under general
      anesthesia were randomly and prospectively assigned to 1 of 2 study groups: group
      saline (group S) and group morphine (group M). After placing an epidural catheter
      at L3-4 or L4-5, patients received either 10 mL of saline or 4 mg of morphine in
      10 mL of saline approximately 60 minutes before anesthesia induction. Anesthesia
      maintenance was provided with desflurane and nitrous oxide in oxygen with a ratio
      of 2:1 by an anesthesiologist blinded to the group. Measurements included BIS
      value, end tidal desflurane concentration, heart rate, and blood pressure before
      surgery and every 10 minutes during surgery. RESULTS: Although there was a
      tendency to slightly lower end-tidal desflurane concentrations in the morphine
      group, this difference did not reach statistical significance at any time. In the
      morphine group, the heart rate was lower than in the saline group at 20, 30, 40,
      and 50 minutes of surgery (P < .05). BIS values were similar throughout surgery.
      CONCLUSIONS: Preoperative administration of epidural morphine does not reduce
      desflurane requirements in patients undergoing gynecologic surgery.

PMID- 16952815
TI  - Single-stimulation, low-volume infraclavicular plexus block: influence of the
      evoked distal motor response on success rate.
AB  - BACKGROUND AND OBJECTIVES: We compared the success rate of single-injection
      infraclavicular plexus block by using electrically evoked radial, ulnar, or
      median nerve-type distal motor response to guide the injection of local
      anesthetic. METHODS: Consecutive patients requiring surgery distal to the upper
      arm were prospectively included in this study over a 6-month period. No search
      for predetermined distal motor responses was performed. The first qualifying
      distal motor response evoked for a stimulating current intensity of <0.5 mA
      distributed patients into 3 groups of patients. The study was continued until 3
      groups of 60 patients were fulfilled. Twenty to 25 minutes after the injection of
      30 mL of 1.5% mepivacaine, blinded evaluation of block quality was performed. A
      successful block was defined by the presence of a complete sensory block of the 5
      major nerve distal distributions of the arm. RESULTS: Five hundred patients were
      included. The first evoked distal motor response was of radial, median, and ulnar
      nerve type in 46% (n = 230), 42% (n = 210), and 12% (n = 60) cases, respectively.
      The success rate of the infraclavicular plexus block was significantly higher
      when the injection was performed on a radial nerve-type response (90%) as
      compared with the median (74%) or ulnar (68%) nerve distal motor response.
      Intraoperative sedation and general anesthesia were not needed. None of the
      patients experienced specific complications. CONCLUSION: We showed that evoked
      distal motor response influenced the success rate of single-injection
      infraclavicular plexus block. The highest success rate was obtained when
      injection was performed after radial nerve-type motor response.

PMID- 16952816
TI  - Ultrastructure of canine meninges after repeated epidural injection of S(+)
      ketamine.
AB  - BACKGROUND: The safety of ketamine when administered by the spinal route must be
      confirmed in various animal species before it is approved for use in humans. This
      study evaluates the ultrastructure of canine meninges after repeated doses of
      epidural S(+)-ketamine. METHODS: Five dogs received S(+)-ketamine 5%, 1 mg/kg,
      twice a day for 10 days through an epidural catheter with its tip located at the
      L5 level. One dog received the same volume of normal saline at the same times.
      The spinal cord and meninges were processed for histopathological and
      ultrastructural studies. Clinical effects were assessed after each injection.
      RESULTS: Motor and sensory block appeared after each injection of S(+)-ketamine,
      but not in the dog receiving saline. No signs of clinical or neurologic
      alterations were observed. Using light microscopy, no meningeal layer showed
      alterations except focal infiltration at the catheter tip level by macrophages,
      lymphocytes, and a few mast cells. The cells of different layers were studied by
      electron microscopy and interpreted according to data from human and other animal
      species because no ultrastructural description of the canine meninges is
      currently available. There were no cellular signs of inflammation, phagocytosis,
      or degeneration in meningeal layers and no signs of atrophy, compression, or
      demyelinization in the areas of dorsal root ganglia and spinal cord around the
      arachnoid. These findings were common for dogs receiving S(+)-ketamine and the
      dog receiving saline. CONCLUSION: Repeated doses of epidural S(+)-ketamine 5%, 1
      mg/kg, twice a day for 10 days was not associated to cellular alterations in
      canine meninges.

PMID- 16952817
TI  - The sensitivity of motor response to nerve stimulation and paresthesia for nerve
      localization as evaluated by ultrasound.
AB  - BACKGROUND AND OBJECTIVE: Seeking paresthesia and obtaining a motor response to
      an electrical stimulus are the two most common methods of nerve localization for
      the performance of peripheral-nerve blocks. However, these two endpoints do not
      always correlate, and the actual sensitivity and specificity of either method
      remains unknown. The objective of this study is to determine the sensitivity of
      paresthesia and motor response to electrical nerve stimulation as tools for nerve
      localization when a 22-gauge insulated needle is used for the performance of
      axillary-nerve block. METHODS: After IRB approval and informed consent, 103
      patients were enrolled. Real-time ultrasonography was used as the reference test.
      After needle-to-nerve contact was confirmed by ultrasonography, the patient was
      requested to report the presence of paresthesia, and a nerve stimulator was used
      to seek a motor response, with a stimulating current of 0.5 mA or less. RESULTS:
      One patient was excluded from analysis because of protocol violation. Paresthesia
      was found to be 38.2% sensitive and motor response was 74.5% sensitive for
      detection of needle-to-nerve contact. CONCLUSION: The very different and
      relatively low sensitivity of either technique may explain, in part, the lack of
      correlation previously reported between the 2 endpoints.

PMID- 16952818
TI  - Ultrasound-guided lumbar medial-branch block: a clinical study with fluoroscopy
      control.
AB  - BACKGROUND AND OBJECTIVES: For diagnostic lumbar medial-branch blocks,
      fluoroscopic guidance is considered mandatory, but this technique comes with
      radiation exposure. The clinical feasibility of the ultrasound-guided lumbar
      medial-branch block has been demonstrated. We evaluated the success rate and
      validity of this new method by use of fluoroscopy controls in patients previously
      diagnosed with lumbar facet joint-mediated pain. METHODS: In 20 patients, 101
      lumbar medial-branch blocks were performed under ultrasound guidance. The target
      point was the groove at the cephalad margin of the transverse process adjacent to
      the superior articular process. C-arm fluoroscopy was performed afterward to
      confirm the needle position. Pain scores were assessed by use of visual analog
      scale (VAS 0 to 100). RESULTS: All 101 needles were placed in the correct lumbar
      segment. Ninety-six of the 101 needletips were in the correct position with a
      success rate of 95%. Two needles were associated with intravascular spread of the
      contrast dye. VAS score was reduced from 52 to 16 after the block. CONCLUSIONS:
      Ultrasound-guided lumbar medial-branch blocks can be performed with a high
      success rate. However, to be completely independent from fluoroscopy controls,
      this technique requires further studies regarding the detection of intravascular
      spread.

PMID- 16952819
TI  - No differences between 20, 30, or 40 mL ropivacaine 0.5% in continuous lateral
      popliteal sciatic-nerve block.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to compare the anesthetic
      and analgesic characteristics of the administration of an initial bolus of 20,
      30, or 40 mL of ropivacaine 0.5% through a lateral popliteal sciatic catheter.
      METHODS: Sixty patients scheduled for foot surgery under continuous sciatic
      lateral popliteal nerve block were included in this double-blinded study.
      Patients were randomly assigned to 1 of 3 groups: 20 mL, 30 mL, or 40 mL of
      ropivacaine 0.5%. Time to obtain a complete sensory block and duration of
      analgesia were recorded. Failure of the continuous block and complications such
      as technical or neurologic problems were noted. RESULTS: Data are presented as
      mean +/- SD, median and ranges, or percent of patients and were compared by
      application of analysis of variance or Kruskal-Wallis when required. Time to
      complete sensory block (31 [10-70] v 25 [5-50] v 25 [5-40] min), percentage of
      failure (5% v 5% v 0%), and duration of action (995 [278-1,800] v 967 [420-2,175]
      v 915 [190-1,900] min) were not statistically different between 20 mL, 30 mL, and
      40 mL ropivacaine 0.5% groups, respectively. No complications were noted.
      CONCLUSIONS: This dose-response study shows that 20 mL of ropivacaine 0.5%
      injected through an indwelling lateral popliteal catheter is the optimal dose for
      foot surgery. Higher doses of 30 mL or 40 mL did not provide any further
      advantage.

PMID- 16952820
TI  - Ganglionic local opioid application (GLOA) for treatment of chronic headache and
      facial pain.
AB  - OBJECTIVE: This report describes the effects of ganglionic local opioid
      application (GLOA) in patients with chronic headache and persistent idiopathic
      facial pain. CASE REPORT: We present 2 patients with chronic headaches and 1
      patient with persistent idiopathic facial pain who were refractory to medical
      treatment. These patients responded well to a series of ganglionic local opioid
      applications (GLOAs) by administration of buprenorphine. The beneficial effect of
      GLOA was manifested by a decrease in pain intensity, reduction of pain
      medications, and improvement in quality of life. CONCLUSIONS: These results
      support the theory of sympathetically mediated pain in the head and face, the
      presence of opioid receptors on the sympathetic ganglia, and a possible
      beneficial role of opioids in modulation of this process. To our knowledge, this
      case series is the first case series in the English literature of the use of GLOA
      at the stellate ganglion for head-and-face pain.

PMID- 16952821
TI  - Use of sequential electrical nerve stimuli (SENS) for location of the sciatic
      nerve and lumbar plexus.
AB  - BACKGROUND AND OBJECTIVES: Conventional electrical stimulation has been done by
      continuous adjustment of current amplitude at a single, set pulse duration
      (conventionally, 0.1 ms). This study evaluated a novel technique for nerve
      location by utilization of a peripheral-nerve stimulator (PNS) programmed to
      deliver sequential electrical nerve stimuli (SENS). A repeating series of
      alternating sequential pulses of 0.1, 0.3, and 1.0 ms at 1/3-second period
      intervals between pulses were generated so that at a greater distance from the
      nerve, only higher-duration pulses would stimulate the targeted nerve and result
      in 1 or 2 motor responses (MR) per second. Three MR per second at 0.5 mA or less
      signified the conventional endpoint for nerve location (</=0.5 mA, 0.1 ms)
      because that value indicated that the 0.1-ms pulse was effective. The
      conventional 0.1-ms pulse served as a built-in control to which the SENS was
      compared. METHODS: Sixteen sciatic/psoas blocks were performed on 8 patients.
      Nerve location was by SENS, with an 80-mm block needle. Needle advance began at
      1.0 mA until MR. If 1 or 2 MR/s occurred, the needle was advanced until 3 MR/s
      were obtained. When 3 MR/s occurred at 0.5 mA or less, needle position was fixed
      (final position), and mA further decreased until MR disappeared. Two digital
      video cameras separately recorded needle depth and MR for analysis. Final needle
      position was designated as zero, and distance was calculated relative to it.
      RESULTS: In 12 of 16 of the performed blocks, SENS resulted in advanced
      notification (1 or 2 MR/s), which yielded additional visual feedback compared
      with control before final nerve location and, thus, increased range. In 15 of 16
      blocks, MR did not disappear, once elicited, through final needle location.
      CONCLUSIONS: SENS resulted in increased sensitivity without compromising
      specificity of nerve location.

PMID- 16952822
TI  - Continuous thoracic paravertebral block for major breast surgery.

PMID- 16952823
TI  - Allergic contact dermatitis caused by ultrasonic gel.

PMID- 16952824
TI  - Epidural hematoma in a patient receiving epidural analgesia and LMWH after total
      knee arthroplasty.

PMID- 16952825
TI  - The importance of ultrasound landmarks: a "traceback" approach using the
      popliteal blood vessels for identification of the sciatic nerve.

PMID- 16952826
TI  - Use of radiographic contrast to confirm the placement of a sciatic catheter in a
      patient presenting an atypical response to neurostimulation.

PMID- 16952827
TI  - A more logical sequence of nerve location when performing multiple-injection
      axillary block.

PMID- 16952829
TI  - Nanoparticles and their biological and environmental applications.
AB  - Nanoparticles exhibit unique physical properties (such as particle aggregation
      and photoemission, and electrical and heat conductivities) and chemical
      properties (such as catalytic activity), and hence have received much attention
      from scientists and researchers in different areas of biological sciences. In
      this review, we briefly summarize the major types of nanoparticle that have been
      used so far and discuss the possible applications of these nanoparticles in
      biological and environmental research, and the potential environmental and health
      impacts associated with the use of these nanoparticles.

PMID- 16952830
TI  - Phenylpropanoid metabolite supports cell aggregate formation in strawberry cell
      suspension culture.
AB  - Plant cells in suspension culture tend to aggregate and form large clumps. In
      suspension culture, large cell aggregates are frequently subjected to
      hydrodynamic shear stress; however, a certain degree of cell aggregation is often
      required for cell growth and metabolite production. Thus, controlling cell
      aggregate size is desired to establish high productivity of useful products using
      plant cell suspension culture. In this study, we focused on the relationship
      between cell-aggregate formation and secondary metabolism. We found that
      anthocyanin concentration showed a good correlation with cell-aggregate size in
      the cultured strawberry cell line FAR (Fragaria ananassa R), which produces
      anthocyanin and other phenylpropanoid metabolites constitutively without
      illumination. This result suggests that there is a relationship between cell
      aggregate formation and the accumulation of phenylpropanoid metabolites. To
      investigate the direct effect of phenylpropanoid metabolism on cell-aggregate
      formation, the time course of cell-aggregate size was monitored when
      phenylpropanoid metabolism was suppressed by a metabolic inhibitor, L-alpha
      aminooxy-beta-phenylpropionic acid (AOPP), a specific inhibitor of phenylalanine
      ammonia lyase which is the starting and key enzyme of the phenylpropanoid
      pathway. In the absence of AOPP, the average diameter of cell aggregates
      increased on day 8 of culture. This increase in cell-aggregate size was
      completely suppressed by the addition of 0.1 mM AOPP, without any reduction in
      cell growth rate or soluble protein content. These results indicate that cell
      aggregate formation is directly supported by a secondary metabolite produced from
      the phenylpropanoid pathway, suggesting that cell-aggregate size can be
      controlled by AOPP without inhibition of primary metabolism.

PMID- 16952831
TI  - Cynomolgus monkey embryonic stem cell lines express green fluorescent protein.
AB  - We successfully established cynomolgus monkey embryonic stem (cES) cell lines
      expressing enhanced green fluorescent protein (GFP) by introducing a GFP-encoding
      gene under cytomegalovirus immediate early enhancer (CMVIE) promoter regulation
      into cES cells. The cells maintained the ability of in vitro differentiation
      toward ectodermal, mesodermal, and endodermal lineages, and produced teratomas
      composed of tissues derived from the three embryonic germ layers when
      transplanted into severe combined immunodeficient disease mice. GFP expression
      was also observed in the differentiated cells. These GFP-expressing cES cell
      lines are considered useful for basic research, including cell transplantation.

PMID- 16952832
TI  - Microbial transformation of aniline derivatives: regioselective biotransformation
      and detoxification of 2-phenylenediamine by Bacillus cereus strain PDa-1.
AB  - A bacterial isolate, strain PDa-1, grew well on basal medium supplemented with 2
      phenylenediamine, sucrose, and ammonium nitrate and completely transformed 2
      phenylenediamine. The isolate was identified as Bacillus cereus. The product
      formed from 2-phenylenediamine was identified by EI-MS and NMR as 2
      aminoacetanilide; whole cells converted 2-phenylenediamine to the product with a
      76% molar yield. Whole cells also showed a broad substrate specificity toward 20
      of 26 tested arylamines with substituent groups of various size and positions.
      Especially 2-aminobenzoic acid, 4-aminosalicylic acid, 5-aminosalicylic acid, and
      2-aminofluorene were converted completely to the corresponding product with an
      aminoacetyl group. Cell extracts of strain PDa-1 had a high arylamine N
      acetyltransferase activity. The partially purified enzyme converted 2
      phenylenediamine to 2-aminoacetanilide. Strain PDa-1 constitutively expressed the
      enzyme in the absence of 2-phenylenediamine. Effects of 2-phenylenediamine and 2
      aminoacetanilide on growth indicated that this enzyme probably plays a role in
      the detoxification of toxic arylamines in this strain.

PMID- 16952833
TI  - Atomic force microscopy observation of highly arrayed phospholipid bilayer
      vesicle on a gold surface.
AB  - Tapping mode atomic force microscopy (TM-AFM) imaging of a phospholipid bilayer
      vesicle (liposome) immobilized on a gold surface was performed to investigate
      morphologies of the electrode surfaces produced through application of three
      different sample preparation methods. We compared both methods from a
      morphological viewpoint using TM-AFM images. Liposomes, composed of zwitterionic
      and anionic phospholipids, were prepared by extrusion. Results indicate that the
      surface with immobilized L1-liposome, which was fabricated by the amino coupling
      method, seemed to form large amounts of aggregated or fused liposomes. In
      contrast, L2-liposome-containing 1-octadecanthiol that was directly attached on
      the gold surface using thiol-gold binding force was immobilized as a uniform
      surface topology without liposome aggregation. Finally, we attempted to arrange
      individual L3-liposome, prepared by mixing zwitterionic and anionic
      phospholipids, onto the gold layer by electron-beam (e-beam) lithography
      technique. A third method, L3-liposome formation on the sensor surface, is
      greatly anticipated for biosensor applications.

PMID- 16952834
TI  - Theoretical analysis of amino acid-producing Escherichia coli using a
      stoichiometric model and multivariate linear regression.
AB  - This work demonstrates a novel computational approach combining flux balance
      modeling with statistical methods to identify correlations among fluxes in a
      metabolic network, providing insight as to how the fluxes should be redirected to
      achieve maximum product yield. The procedure is demonstrated using the example of
      amino acid production from an industrial Escherichia coli production strain and a
      hypothetical engineered strain overexpressing two heterologous genes. Regression
      analysis based on a random sampling of 5,000 points within the feasible solution
      space of the E. coli stoichiometric network suggested that increased activity of
      the glyoxylate cycle or PEP carboxylase and elimination of malic enzyme will
      improve lysine and arginine synthesis.

PMID- 16952835
TI  - Dynamic seeding and perfusion culture of hepatocytes with galactosylated
      vegetable sponge in packed-bed bioreactor.
AB  - A galactose moiety was introduced into the fiber surface of a vegetable sponge by
      the covalent binding of lactobionic acid. The galactosylated sponge was used as
      scaffold for the culture of rat hepatocytes in a packed-bed bioreactor.
      Hepatocytes could be dynamically seeded into and uniformly distributed throughout
      the scaffold, and the immobilized cells maintained high albumin and urea
      production rates during long-term perfusion culture. The hepatocytes showed an
      increasing albumin production rate from 49 to 109 microg/10(6) cells/d over the 7
      d culture.

PMID- 16952836
TI  - Classification of intramural metastases and lymph node metastases of esophageal
      cancer from gene expression based on boosting and projective adaptive resonance
      theory.
AB  - Esophageal cancer is a well-known cancer with poorer prognosis than other
      cancers. An optimal and individualized treatment protocol based on accurate
      diagnosis is urgently needed to improve the treatment of cancer patients. For
      this purpose, it is important to develop a sophisticated algorithm that can
      manage a large amount of data, such as gene expression data from DNA microarrays,
      for optimal and individualized diagnosis. Marker gene selection is essential in
      the analysis of gene expression data. We have already developed a combination
      method of the use of the projective adaptive resonance theory and that of a
      boosted fuzzy classifier with the SWEEP operator denoted PART-BFCS. This method
      is superior to other methods, and has four features, namely fast calculation,
      accurate prediction, reliable prediction, and rule extraction. In this study, we
      applied this method to analyze microarray data obtained from esophageal cancer
      patients. A combination method of PART-BFCS and the U-test was also investigated.
      It was necessary to use a specific type of BFCS, namely, BFCS-1,2, because the
      esophageal cancer data were very complexity. PART-BFCS and PART-BFCS with the U
      test models showed higher performances than two conventional methods, namely, k
      nearest neighbor (kNN) and weighted voting (WV). The genes including CDK6 could
      be found by our methods and excellent IF-THEN rules could be extracted. The genes
      selected in this study have a high potential as new diagnosis markers for
      esophageal cancer. These results indicate that the new methods can be used in
      marker gene selection for the diagnosis of cancer patients.

PMID- 16952837
TI  - Enhancement of styrene removal efficiency in biofilter by mixed cultures of
      Pseudomonas sp. SR-5.
AB  - The styrene-degrading bacterium Pseudomonas sp. SR-5 exhibited a high styrene
      removability in a biofilter. However, the styrene removal efficiency (RE) of SR-5
      decreased with time. We carried out styrene gas removal in a biofilter inoculated
      with mixed cultures of SR-5 and other microorganisms to determine the possibility
      of obtaining an enhanced RE for a long period. The following three inocula were
      carried out: (i) styrene-degrading bacteria, strains 1 and 3, (ii) a benzoic acid
      degrading bacterium Raoultella sp. A, and (iii) wastewater from a chemical
      company dealing with styrene. These biofilters with mixed SR-5 showed an enhanced
      RE compared with those with a single culture of SR-5. The complete styrene
      elimination capacities for ensuring 100% styrene removal in those mixed cultures
      were 151, 108 and 124 g/m(3)/h, compared with a single culture of SR-5.

PMID- 16952838
TI  - Novel poly-gamma-glutamate-processing enzyme catalyzing gamma-glutamyl DD
      amidohydrolysis.
AB  - The pgdS gene product of Bacillus subtilis, PgdS, cleaves poly-gamma-glutamate
      (PGA) in an endo-peptidase-like fashion. However, its catalytic property remains
      obscure. In this study, a simple assay for the PgdS enzyme using 1-fluoro-2,4
      dinitrobenzene was developed, and some characteristics of PgdS, such as optimal
      pH, were examined. The enzyme was strongly inhibited by a thiol-modifying
      reagent, suggesting that it possesses essential cysteine residue(s) in catalysis.
      PgdS exhibited a high affinity to PGA that consisted mainly of D-glutamate
      residues, but no affinity to PGA composed only of L-glutamate residues (L-PGA).
      The enzyme processed DL-copolymer-type PGA (DL-PGA) with an average molecular
      mass of 1,000 kDa to a high-molecular-mass L-glutamate-rich fragment (average 200
      kDa), the L-rich PGA fragment, and low-molecular-mass fragment composed mostly of
      D-glutamate residues (average 5 kDa), D-fragment. To deepen our understanding of
      the catalytic property of the PgdS enzyme, we analyzed the structures of the N-
      and C-terminal regions and found that D-glutamyl residues successively lie even
      at both ends of the L-rich PGA fragment. Our observations indicate that PgdS is a
      novel endo-peptidase that specifically cleaves the gamma-amide linkage between
      two D-glutamate residues in PGA, i.e., gamma-glutamyl DD-amidohydrolase. The
      enzyme is possibly useful in the biochemical processing of B. subtilis DL-PGA.

PMID- 16952839
TI  - Thermal inactivation of immobilized lipase in 1-alcohols.
AB  - The thermal inactivation of immobilized lipase from Candida antarctica in 1
      alcohols with four to eight carbons at various temperatures could be well
      expressed using a model in which heterogeneity in the susceptibility of the
      enzyme to the inactivation was assumed. It was found that the enthalpy-entropy
      compensation held for inactivation in 1-alcohols.

PMID- 16952840
TI  - Performance of expression vector, pTD1, in insect cell-free translation system.
AB  - We constructed a pTD1 vector for an insect cell-free translation system
      containing a 5' untranslated region (UTR) of a polyhedrin gene as a translational
      enhancer sequence. Its translational efficiency was about 50-fold higher than
      those of mRNAs without an enhancer sequence. Moreover, the pTD1 vector functioned
      as an effective expression vector not only in the insect cell-free translation
      system but also in wheat germ extract and rabbit reticulocyte lysate systems.

PMID- 16952841
TI  - Surgical management of peritoneal carcinomatosis: from clinical research to
      standard of care.

PMID- 16952842
TI  - Cancer and aging.

PMID- 16952843
TI  - Molecular biology in acute leukemia.
AB  - Acute leukemia is a clonal expansion of tumoral cells in bone marrow, blood or
      other tissues. The acute leukemias are classified as myeloid or lymphoid based on
      the lineage of the blast cells. Over the past three decades, remarkable advances
      have been made in the classification and treatment of acute leukemias. In the
      last years, the research into the molecular pathogenesis of acute leukemia has
      progressed. The knowledge of chromosomal translocations breakpoints and possible
      candidate oncogenes and tumor suppressor genes has allowed the integration of all
      these events into multistep cascades that impact specific signal transduction
      pathways and lead to leukemic transformation.

PMID- 16952844
TI  - Therapeutic opportunities and targets in childhood leukemia.
AB  - Childhood leukemia is a common pediatric cancer in the developed world, the
      disease is biologically diverse and there is much discussion as to its causal
      mechanisms. Acute lymphoblastic leukemia (ALL) is the most common subtype and
      infants with ALL have a greatly increased risk of treatment failure. There are
      molecular and biological properties of leukemic cells that determine treatment
      outcome; these can usually be attributed to distinct genetic abnormalities that
      alter the normal proliferative and survival signals of hematopoietic cells.
      Experimental evidence for the existence of leukemic stem cells (LSC) has been
      obtained, and it is presumed that these cells arise from mutations in normal
      hematopoetic stem cells or progenitor cells, and they are difficult to eradicate.
      LSC seem to be surprisingly different from their normal counterparts and
      therefore are obvious new targets for drug therapy. Therapeutic concepts using
      monoclonal antibodies have substantially improved response rates in patients with
      malignant lymphomas and are currently being evaluated in other types of cancer.

PMID- 16952845
TI  - Contributions of advanced proteomics technologies to cancer diagnosis.
AB  - The ability of Medicine to effectively treat and cure cancer is directly
      dependent on their capability to detect cancers at their earliest stages. The
      advent of proteomics has brought with it the hope of discovering novel biomarkers
      in the early phases of tumorigenesis that can be used to diagnose diseases,
      predict susceptibility, and monitor progression. This discipline incorporates
      technologies that can be applied to complex biosystems such as serum and tissue
      in order to characterize the content of, and changes in, the proteome induced by
      physiological changes, benign or pathologic. These tools include 2-DE, 2D-DIGE,
      ICAT, protein arrays, MudPIT and mass spectrometries including SELDI-TOF. The
      application of these tools has assisted to uncover molecular mechanisms
      associated with cancer at the global level and may lead to new diagnostic tests
      and improvements in therapeutics. In this review these approaches are evaluated
      in the context of their contribution to cancer biomarker discovery. Particular
      attention is paid to the promising contribution of the ProteinChip/SELDI-TOF
      platform as a revolutionary approach in proteomic patterns analysis that can be
      applied at the bedside for discovering protein profiles that distinguish disease
      and disease-free states with high sensitivity and specificity. Understanding the
      basic concepts and tools used will illustrate how best to apply these
      technologies for patient benefit for the early cancer detection and improved
      patient care.

PMID- 16952846
TI  - New target-based agents involve new clinical trial designs.
AB  - Clinical cancer investigation is performed through clinical trials. Development
      and measurement of clinical efficacy of new target-based agents differs from
      classic cytotoxic drugs. Whereas the aim of chemotherapy drugs is to destroy
      tumoral cells, new agents try to inhibit cell profileration without a clear tumor
      shrinkage. The main endpoint for phase I trials is to determine the optimal
      biological response with the least toxicity; oncopharmacogenomic studies must be
      performed in tumoral biopsies to assess the target inhibition. Time to
      progression and biological activity are the endpoints for phase II studies.
      Finally, phase III trials will determine overall survival.

PMID- 16952847
TI  - Epidemiological pattern and time trends in testicular germ-cell tumors: a single
      institution 20-year experience.
AB  - INTRODUCTION: Recent studies have suggested a rise in the incidence of testicular
      germ-cell tumors (TGTs) in the last years, mainly due to an increase of early
      stage cases. We analysed the time trends in biological features of these patients
      in order to confirm this tendency in our environment. MATERIALS AND METHODS: The
      clinical records of 136 consecutive patients with TGTs treated at a single
      institution over a 20-year period (1984-2003) were retrospectively reviewed.
      Pathological, clinical, therapeutic and outcome data were collected. Patients
      were allocated into four consecutive 5- year intervals and their characteristics
      were compared by means of the chi-squared test. The survival analysis was
      performed with the method of Kaplan and Meier. RESULTS: A progressive increase in
      the incidence of new cases, and a more frequent diagnosis of stage I versus stage
      II-IV disease was confirmed within this time period. It was also observed a
      greater use of postorchiectomy chemotherapy, mainly due to an increase in the
      adjuvant indications. A significant decrease in the recurrence rate was noted.
      Ten-year overall survival was 86.5%. There was a trend for improved outcome, but
      the differences among the two decades were not statistically significant.
      CONCLUSIONS: A real increase in the incidence of TGTs and in the proportion of
      early stages was confirmed. This may be due to an epidemiological change or to an
      earlier diagnosis. This new pattern is associated with a more frequent use of
      adjuvant chemotherapy and with a reduction in the relapse rate.

PMID- 16952848
TI  - Gastrointestinal stromal tumors: experience in 49 patients.
AB  - INTRODUCTION: Gastrointestinal stromal tumours (GIST) are mesenchymal tumours of
      the digestive tract originated in the interstitial cells of Cajal. They express
      the tyrosine kinase c-kit (CD117) activity receptor. Mutations in this receptor
      cause neoplastic development. Curative treatment continues to be radical
      resection of the tumour and is resistant to commonly employed chemotherapy
      regimens. Imatinib mesilate is a drug that inhibits c-kit activity expressed by
      GIST and its activity in these tumours has been demonstrated. MATERIAL AND
      METHODS: Retrospective study of all cases of leiomyoma, leiomyosarcoma,
      schwannoma, and stromal or mesenchymal tumors from 1989 to July 2004. C-kit and
      CD34 proteins were detected at immunohistochemical study in addition to the usual
      markers for mesenchymal tumours. RESULTS: 49 GISTs were diagnosed, 26 males and
      23 females (mean age 64.1). Symptoms were digestive tract bleeding (n = 13),
      abdominal pain (n = 13), intestinal occlusion (n = 4) and others. The lesion was
      located in small bowel (n = 22), stomach (n = 19), rectum (n = 3), peritoneum (n
      = 2), esophagus (n = 1), omentum (n = 1), and retroperitoneum (n = 1). Forty
      three of the 49 patients underwent surgery; radical resection was performed in 37
      (75.5%) and palliative surgery in the other six (16.2%). Two of the patients that
      did not undergo surgery received chemotherapy. At the time of study, 28 (57.14%)
      patients remained alive, 23 (46.9%) of whom were disease- free and five (10.2%)
      were not. Nineteen (38.7%) patients died. CONCLUSIONS: The results of our series
      are similar to the others published. Before the year 2001, surgery was the only
      successful option for the GIST. Surgical resection continues being the best
      treatment to definitively cure this disease. Imatinib is used to treat not only
      resectable tumours, but even to allow the possibility to make a subsequent rescue
      surgery. On the other hand, Imatinib is used in the treatment of the metastatic
      disease.

PMID- 16952849
TI  - Impact of neoadjuvant hormonal therapy on dose-volume histograms in patients with
      localized prostate cancer under radical radiation therapy.
AB  - INTRODUCTION: Prostate volume involves a defined toxicity predictor in the
      radiation therapy of localized prostate cancer. Neoadjuvant hormone therapy (nHT)
      can reduce prostate volume and, therefore, the planned volume. The objective of
      this study was to establish if the value of nHT reduces the planned volume and if
      this reduction correlates with a reduction of the dose received in the target
      organs. MATERIAL AND METHODS: 28 patients diagnosed of localized prostate cancer
      and referred to our departments for radiation therapy with radical intention, in
      the period ranging between April 2002 and October 2003, were included
      prospectively. The patients received nHT (triptorelin + flutamide) for 2 months
      and adjuvant HT until completing 2 years in the high-risk cases. A transrectal
      ultrasound study was performed in all patients, simulation CT and planning before
      the start of HT and after 2 months of treatment. The radiation therapy was
      carried out with 6 or 18 MV LINAC photons, with a dose fractioning scheme of 5 x
      180-200 cGy, a total dosage of 66-72 Gy to prostate, 56 Gy to seminal vesicles
      and, in the high-risk cases, 46 Gy to pelvic lymph nodes. RESULTS: The
      distribution according to risk group was: low risk 3.6%, intermediate risk 28.6%
      and high risk 67.9%. By transrectal ultrasound, prostate volume on diagnosis was
      50.65 cc pre HT and 38.97 cc post HT (p < 0.001), which means a volume reduction
      of 24%. The comparative analysis of the dose-volume histograms of the first
      versus the second CT shows a reduction in the planned volume GTV1 (prostate)
      (81.33 cc vs 63.96 cc, p < 0.05), PTV1 (prostate and margin) (197.51 cc vs 168.38
      cc, p < 0.001) and PTV2 (prostate, vesicles and margin) (340.5 cc vs 307.26 cc, p
      < 0.05), a reduction of the maximum dose in the seminal vesicles (70.2 versus
      68.75 Gy, p < 0.05), a reduction of the mean dose in the seminal vesicles (65.07
      Gy versus 63.07 Gy, p < 0.05), PTV2 (67.72 Gy versus 66.9 Gy, p < 0.01) and PTV3
      (prostate, vesicles, pelvic lymph nodes and margin) (58.86 Gy versus 57.21 Gy, p
      < 0.01), a reduction of the D90 in the seminal vesicles (61.83 Gy versus 60.06
      Gy, p < 0.05) and PTV2 (61.04 Gy versus 59.45 Gy, p < 0.05) and a reduction of
      V60 of the rectum (32.45% versus 28.22%, p < 0.05) and V60 of the bladder (41.78%
      versus 31.67%, p < 0.005). CONCLUSIONS: Neoadjuvant hormone therapy reduces
      significantly prostate volume and as a result the planned volume and consequently
      the rectal and bladder V60 can be significantly reduced.

PMID- 16952850
TI  - Dermatofibrosarcoma protuberans: review of 20-years experience.
AB  - INTRODUCTION: Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue
      neoplasm with low-intermediate grade of malignancy. It is a locally aggressive
      tumour with a high recurrence rate. Surgical excision with adequate margins is
      the main treatment. MATERIALS AND METHODS: We describe the clinicopathological
      features of 21 cases of DFSP. The mean size of the lesions was 5.6 cm, mostly
      located in trunk. 61.9% of the cases underwent surgical excision without previous
      biopsy. 52.4% of the patients presented positive margins, that required surgical
      extension. RESULTS: The recurrence rate was 28.6% (6 cases), five of them local
      recurrences treated with new surgical excision with wide margins. Median period
      free of illness was 32.5 months. Medium follow-up period was 33.25 months.
      CONCLUSIONS: DFSP has a locally high recurrence rate, that has been associated to
      inadequate surgical margins. The histological knowledge preoperatively would
      permit surgical excision with adequate margins, and probably this could reduce
      the recurrence rate. Radiotherapy could avoid the surgical extension of margins
      in these cases with positive ones. Chemotherapy could be indicated in metastasic
      cases. Most recurrences appear in the first 3 years, but it is important a long
      term follow-up of these patients.

PMID- 16952851
TI  - Evaluation of the toxicity of the combined treatment of chemoradiotherapy,
      according to the scheme of Macdonald, after radical surgery in patients diagnosed
      of gastric cancer.
AB  - PURPOSE: In this study we evaluated the acute toxicity of the combined treatment
      with chemoradiotherapy, according to the scheme of McDonald et al, in patients
      diagnosed with gastric cancer, after radical curative surgery. METHODS: From July
      2001 to December 2005, a total of 24 patients, with diagnosis of adenocarcinoma
      of the stomach or adenocarcinoma of the gastroesophageal junction, who were
      operated with total or subtotal gastrectomy with free resection margins, were
      treated at our service with a combined scheme of adjuvant chemoradiotherapy.
      RESULTS: Grade 3 toxicity or higher appeared in three patients (12%) and grade 2
      in five of the twenty-four patients (21%). Two patients (8%) needed to suspend
      treatment before the scheduled end date of treatment due to acute toxicity. No
      acute toxicity of cardiological, hepatic or renal nature was registered, and the
      most frequent toxicity was the gastrointestinal toxicity (detected in the 79% of
      the patients). CONCLUSIONS: Combined treatment with chemoradiotherapy, according
      to the scheme of Macdonald, in diagnosed patients with gastric cancer, after
      radical curative surgery is a well tolerated treatment, with a low degree of
      acute toxicity, thus the treatment compliance is not difficult.

PMID- 16952852
TI  - Skin metastases as first manifestation of lung cancer.
AB  - Skin metastases as manifestation of internal neoplasias constitute a 0.8% of
      their initial presentation and generally imply an advanced stage of the disease
      and a short survival. The lung cancer metastasises to the skin in 2.8-24% of the
      cases, generally in advanced stages of the disease, although in 7-19%, skin
      metastases appear as first manifestation thereof. Sometimes, the study of the
      extent in the patients reveals that there are no metastases at other levels. We
      hereby present the case of a male diagnosed with a lung cancer whose first
      manifestation was the appearance of skin metastases.

PMID- 16952853
TI  - Positron emission tomography: a false negative result in cystic encephalic
      mestastases from a small cell bronchial carcinoma.
AB  - Lung cancer represents one of the most common malignant diseases. Many
      investigations are used in the staging study including, most recently, PET. We
      present a case of cystic cerebral metastases (with no oedema) from a small cell
      carcinoma which were not detected by PET.

PMID- 16952854
TI  - Cushing's paraneoplastic syndrome as first manifestation of an adenocarcinoma of
      unknown origin.
AB  - Small cell lung cancer is the most common cause of paraneoplastic Cushing's
      syndrome. The definitive treatment consists in surgical removal of the tumour,
      which is not possible in most of these cases (they are often diagnosed at
      advanced stages), and therefore it is frequently necessary adding the drug
      ketoconazol. We hereby present the case of a patient diagnosed with a metastatic
      carcinoma of unknown origin associated with two paraneoplastic syndromes: a
      Cushing's syndrome and a sensitive-motor axonal neuropathy, a very uncommon
      association.

PMID- 16952855
TI  - Pulmonary toxicity of 5-fluoracil and oxaliplatin.

PMID- 16952856
TI  - Non-invasive measurement of airway inflammation in asthma.
AB  - Assessing the severity and control of a patient's asthma is of great importance
      to ensure that pharmacotherapy is optimized. Measures such as lung function,
      symptoms, and reliever use have traditionally been used as objective means of
      undertaking this assessment, but until now the level of airway inflammation has
      not been quantified. As asthma is primarily an inflammatory disorder, it would be
      desirable to include a measure of this process when evaluating disease control.
      The following article outlines methods of non-invasively measuring asthmatic
      airway inflammation and highlights their potential role in clinical practice.

PMID- 16952857
TI  - Exhaled nitric oxide levels are not correlated with eczema severity in Chinese
      children with atopic dermatitis.
AB  - Asthma is a common atopic disease associated with atopic dermatitis (AD) and
      allergic rhinitis (AR). Exhaled nitric oxide level (eNO) has been found to be an
      interesting noninvasive marker of disease severity in children with asthma.
      However, it is uncertain if eNO may be confounded by any coexisting AD or AR. In
      this study, eNO in Chinese children with moderate-to-severe AD and no asthma
      symptoms (n = 53) was measured online by a chemiluminescence analyzer. Severity
      of AD was assessed using the objective SCORing-Atopic-Dermatitis score and
      coexisting allergic rhinitis with the Allergic-Rhinitis-Score (ARS). Patients
      with active symptoms of asthma or inhaled/intranasal corticosteroids were
      excluded. There was no difference in eNO between genders and no correlation
      between eNO and AD severity regardless of ARS or bronchial reactivity status. ENO
      appears to be a noninvasive marker whose level is independent of the two atopic
      diseases of AD and AR in children old enough to perform exhalation maneuver.

PMID- 16952858
TI  - Sensitization to Alternaria and Cladosporium in patients with respiratory allergy
      and outdoor counts of mold spores in Ankara atmosphere, Turkey.
AB  - Sensitization to Alternaria and Cladosporium has been reported to be 3% to 30% in
      European countries. However, in Turkey, there is limited data about the
      prevalence of sensitization to these molds and the intensity of the two mold
      spores in Ankara atmosphere. This study was designed to evaluate the
      sensitization to Alternaria and Cladosporium in patients with respiratory allergy
      in Ankara and also the concentration of the two molds in Ankara atmosphere.
      Allergic rhinitis and asthma patients living in Ankara were included in the
      study. Demographic and diagnostic data of the patients were recorded. A skin
      prick test with extracts supplied by three different laboratories was used to
      evaluate the sensitization to Alternaria and Cladosporium. Mold spores were
      measured using a Burkard 7-day recording volumetric spore trap in Ankara
      atmosphere during a year. Overall sensitization to the two molds was found to be
      14.8%, and isolated Alternaria or Cladosporiumsensitization was 3%. Considering
      the positive reaction to at least one of the three suppliers, the sensitization
      rate was 11.9% and 8.1% for Alternaria and Cladosporium, respectively. Cochran's
      Q homogenization test demonstrated that the positive and negative reaction were
      not homogeneous among three laboratories. The total number of mold spores in
      Ankara atmosphere was 429,264 spores/m3 of which 75.5% and 6% were constituted by
      Cladosporium and Alternaria, respectively. The prevalence of Cladosporium and
      Alternaria sensitization in respiratory allergy patients is quite similar to
      European countries; however, our data indicate that commercial mold extracts
      should be standardized to establish the real sensitization rates. Additionally,
      considering the great numbers of these mold spores in Ankara atmosphere, long
      term follow-up studies are needed to evaluate the relationship between the mold
      load and sensitization patterns.

PMID- 16952859
TI  - Bronchial asthma showing reduction in FEV1 after inhalation of Qvar.
AB  - The administration of Qvar (a hydrofluoroalkane-134a beclomethasone dipropionate;
      HFA-BDP) is highly useful for the treatment of patients with asthma. However, we
      found in a case of bronchial asthma that replacing the prior inhaled
      corticosteroids with Qvar resulted in temporary dyspnea and reduction in forced
      expiratory volume in 1 second (FEV1). Qvar contains beclomethasone dipropionate
      combined with absolute ethanol and an alternative to fluorocarbon. The patient
      had complicated alcohol-induced asthma. FEV1 decreased markedly and immediately
      after Qvar inhalation. The Qvar placebo is free of beclomethasone but contains
      other ingredients (ethanol and fluorocarbon). FEV1 did not decrease after the
      Qvar placebo, Aldecin inhalation, and Qvar inhalation orally treated with
      atropine before inhalation of Qvar. It seems unlikely that the components of Qvar
      (except beclomethasone) are responsible for the reduction in FEV1 observed
      immediately after inhalation of Qvar. These findings would be noteworthy when
      using Qvar for Japanese patients with asthma known to have a relatively high
      frequency of the complication of alcohol-induced asthma.

PMID- 16952860
TI  - Catalytic hydrolysis of VIP in pregnant women with asthma.
AB  - RATIONALE: The neuropeptide vasoactive intestinal peptide (VIP) is one of the
      physiologic mediators of non-adrenergic, non-cholinergic smooth muscle relaxation
      of the airway and an important modulator of innate and adaptive immune responses.
      VIP catalytic autoantibodies are increased in asthma and serum VIP level is
      decreased during acute exacerbation of asthma. The effect of pregnancy on asthma
      is variable and depends in part on the severity of pre-existing asthma, along
      with other physiological and pathophysiological changes. We hypothesized that
      hydrolysis of VIP by circulating catalytic VIP antibodies will be increased in
      pregnancy in patients with asthma. STUDY OBJECTIVE: To determine the level of
      catalytic autoantibodies to VIP in pregnant asthmatics compared to non-pregnant
      asthmatics and control pregnant women without asthma. METHODS: We prospectively
      enrolled eight pregnant asthmatics (age, 26.5 +/- 2.6 years; mean +/- SEM), nine
      pregnant women without asthma (32.0 +/- 3.0 years), seven non-pregnant women with
      asthma (25.0 +/-1.9 years), and seven non-pregnant women without asthma (34.4 +/-
      2 years) into the study. VIP hydrolysis was performed in all subjects. RESULTS:
      Immunoglobulin G (IgG) autoantibodies that catalyze the hydrolysis of vasoactive
      intestinal peptide (VIP) were present at greater levels in the blood of pregnant
      women with asthma (7.6 +/- 1.1 pM VIP/6 h) compared to pregnant women without
      asthma (4.0 +/- 0.5; p < 0.001), non-pregnant asthmatics (4.9 +/- 0.9; p < 0.05)
      or non-pregnant women without asthma (1.9 +/- 0.7; p < 0.05). CONCLUSION: An
      increase in the VIP hydrolyzing activity of IgG is independently associated with
      asthma and pregnancy. The autoantibodies hold the potential of affecting the
      pathophysiology of the airways in pregnant asthmatics.

PMID- 16952861
TI  - Adapting to asthma: are some asthma effects acceptable?
AB  - Health-related quality-of-life scores depend on patients' judgments about their
      condition and its effect on them. Asthma is a long-term disease, and it is
      possible that patients may learn to accept some of its effects. We tested the
      hypothesis that patients come to accept some asthma effects and then discount
      them as being important when rating their health. We asked patients which of the
      asthma effects listed in the St. George's Respiratory Questionnaire were
      acceptable to them. This enabled us to calculate a score for effects of asthma
      that patients experienced, yet were acceptable to them. The comparative validity
      of the Current, Acceptable and Unacceptable St George's Respiratory Questionnaire
      scores was examined by testing their correlations with a variety of asthma
      related variables. Eighty patients participated, mean age 50 years, mean forced
      expiratory volume in 1 second (FEV1) 73 (SD 24)% predicted. Acceptability of St
      George's Respiratory Questionnaire items was related to the previously identified
      severity weights (rho = -0.65, p < 0.0001), but some severe effects were
      acceptable to some patients. Patients who accepted higher levels of health
      impairment were older with more severe disease. Unacceptable health was less well
      correlated with asthma-related variables than was current health. We conclude
      that patients accept some asthma effects but do not appear to discount them when
      using a detailed health status questionnaire.

PMID- 16952862
TI  - Association of atopy to asthma severity and medication use in children.
AB  - The importance of aeroallergens as triggers for asthma is well recognized, but
      the relationship between asthma severity and atopic profiles in childhood has not
      been elucidated. This study assessed the relationship of allergen sensitization
      to asthma severity in a study of 114 asthmatic children followed for 8 weeks in
      three Southern California areas. Increased controller medication and beta-agonist
      use were positively associated with number of positive skin tests and allergy to
      mold and pollens. Mold was associated with increased asthma symptoms. Degree of
      atopy and reactivity to mold and pollens plays a significant role in asthma
      severity in asthmatic children.

PMID- 16952863
TI  - Association of excess weight and degree of airway responsiveness in asthmatics
      and non-asthmatics.
AB  - It is unclear whether obesity is associated with increasing degree of airway
      responsiveness in asthmatics. In this study, methacholine challenge test results
      of 1,725 subjects with respiratory symptoms were reviewed. Obesity was associated
      with asthma with an odds ratio of 1.72 (95% C.I. 1.36, 2.17). Although there was
      a significant difference in the degree of airway responsiveness between various
      body mass index categories of non-asthmatics (p = 0.01), no significant
      difference was noted among asthmatics (p = 0.93). A weakly significant
      interaction between asthma status and body mass index on the degree of airway
      responsiveness was noted (p = 0.08).

PMID- 16952864
TI  - Environmental allergens and asthma morbidity in low-income children.
AB  - Asthma morbidity is high in inner-city children in the United States, which may
      be related in part to increased allergens in poorly maintained housing. This
      study examined asthma morbidity in relation to mold, cockroach, dust mite, and
      cat allergens in the homes of 61 low-income Chicago children with asthma.
      Children exposed to higher levels of Penicillium in the bedroom had more frequent
      asthma symptoms, whereas those exposed to higher levels of cockroach allergen in
      the bedroom had a higher number of asthma symptoms. Respiratory infections
      confounded the association of cockroach allergen with number of asthma symptoms.

PMID- 16952865
TI  - Proficiency of pediatricians in the use of inhaled medication delivery systems
      for the management of asthma.
AB  - OBJECTIVE: To evaluate the proficiency of pediatricians in the demonstration of
      the proper use of metered-dose inhalers (MDIs) and to assess their theoretical
      knowledge of inhalation devices used in the management of asthma. DESIGN:
      Prospective cross-sectional survey. SETTING: Two university-affiliated hospitals.
      PARTICIPANTS: Seventy-one pediatricians and pediatric house staff. INTERVENTION:
      Each pediatrician's technique was graded by two trained observers using a
      checklist of six essential steps recommended by national guidelines. Theoretical
      knowledge of asthma devices was evaluated by a written questionnaire. RESULTS:
      Twenty (35.2%) pediatricians performed at least five steps correctly, 28 (39.4%)
      performed three or four steps correctly, and 18 (25.4%) performed two steps or
      less correctly. The most common errors were failure to start inhalation from
      functional residual capacity, failure to inhale slowly, and failure to wait at
      least 20 seconds before the next puff. Senior pediatricians were more skillful in
      the practical use of MDIs than were pediatric house staff (p = 0.03). The most
      common deficiencies in theoretical knowledge were related to estimation of the
      amount of medication in the canister (8.5% correct) and how valved holding
      chambers (VHCs) improve drug delivery to the lung (15.5% correct). CONCLUSION:
      Pediatricians in Kuwait have significant deficiencies regarding the practical and
      theoretical aspects of MDIs and other inhalation devices.

PMID- 16952866
TI  - Dyspnea perception and reversibility of methacholine-induced unlimited airway
      narrowing in asthmatics.
AB  - The hypothesis was that asthmatics might experience impaired perception of
      dyspnea and salbutamol-induced reversibility during unlimited airway narrowing. A
      total of 38 asthmatics (18 to 59 years of age) were examined. All patients
      underwent the methacholine challenge test. According to the dose-response curve
      to methacholine, they were categorized as having either unlimited airway
      narrowing (UAN group) (n = 20) or response plateau (RP group) (n = 18).
      Reversibility of methacholine-induced bronchoconstriction was measured 20 minutes
      after the inhalation of 400 microg of salbutamol to compare postbronchodilator
      FEV1 with baseline FEV1. Dyspnea perception was evaluated using the Borg Scale to
      calculate a perception score at a 20% decrease in FEV1 (PS20) and the slope alpha
      of the regression line between the changes in Borg scores and the reduction in
      FEV1 as percentage of the baseline value. Subjects in the UAN group exhibited
      significantly lower PS20 compared with the RP group (1.45+/- 0.23 vs. 2.84 +/-
      0.35, p = 0.002); the mean of the slope values was higher in the RP group than it
      was in the UAN group (0.150 +/- 0.015 vs. 0.095 +/- 0.006, p = 0.003). Salbutamol
      induced reversibility was significantly lower in the UAN group (81 +/- 1.4 % of
      baseline FEV1) compared with patients from the RP group (91 +/- 1.1% of baseline
      FEV1; p < 0.001). In conclusion, asthmatics during methacholine-induced unlimited
      airway narrowing exhibit diminished perception of dyspnea and lower bronchial
      reversibility to the baseline 20 minutes after inhalation of salbutamol. This
      suggests that more careful monitoring of the lung function for timely recognition
      of asthma deteriorations and adequate bronchodilatory therapy during severe acute
      attacks should be recommended for such patients.

PMID- 16952867
TI  - Patient characteristics associated with nocturnal emergency department visits for
      asthma.
AB  - STUDY OBJECTIVES: To identify patient characteristics associated with nocturnal
      emergency department (ED) visits for asthma. METHODS: Asthmatic patients 18 to 55
      years of age who visited Ontario EDs between April 1, 2003 and March 31, 2004,
      were identified through an administrative clinical database. Patients' time of ED
      presentation was analyzed for circadian pattern using histogram and polynomial
      regression. Risk of nocturnal visit (presentation at the ED between midnight and
      8 AM) was modeled through generalized estimating equations with patient age,
      gender, and asthma severity level as covariates. The effect of nocturnal visit on
      return rate to the ED within 14 days after the initial visit was determined
      through Cox regression. RESULTS: During study period there were 31,490 ED visits
      for asthma made by 23,253 patients. Their time of ED visits displayed a distinct
      circadian pattern with peak between 7 and 8 PM, and trough at 5 AM. Approximately
      22% of visits (6,868) occurred at night. Men had higher odds of presenting at
      night than women (OR 1.61; 1.49-1.73). Patients with mild asthma were
      significantly less likely to visit the ED at night than patients with moderate or
      severe asthma. Nocturnal presentation was not associated with higher odds of
      subsequent returns to the ED (HR 1.00; 0.89-1.14). CONCLUSION: Higher odds of
      nocturnal visits in men suggest the existence of gender-differences in health
      seeking behavior in asthmatics. Although nocturnal visits are associated with
      more severe asthma, they do not lead to higher return rates.

PMID- 16952870
TI  - Antibodies to lipids and liposomes: immunology and safety.
AB  - Naturally occurring antibodies to phospholipids and cholesterol are widespread;
      they occur commonly during the course of acute infections; they are not causally
      related to the anti-phospholipid syndrome; they have been associated with other
      clinical entities only as an epiphenomenon; and they have not been implicated as
      causing any clinical syndrome or disease. There are theoretical and experimental
      reasons to believe that normal cells and tissues are protected from binding of
      antibodies to bilayer lipids by steric hindrance due to adjacent larger
      molecules, such as large or charged adjacent glycolipids or proteins on the cell
      surface. There are also reasons to believe that certain natural antibodies to
      lipids can even serve useful normal functions. Antibodies to liposomal lipids
      induced by liposomes containing lipid A appear to have characteristics that are
      similar or identical to naturally occurring antibodies to lipids, and it is
      therefore believed that such antibodies would not cause adverse clinical effects.
      Numerous Phase I and II human clinical trials of experimental vaccines containing
      liposomes and lipid A have shown a high level of safety.

PMID- 16952871
TI  - Activation of the human complement system by cholesterol-rich and PEGylated
      liposomes-modulation of cholesterol-rich liposome-mediated complement activation
      by elevated serum LDL and HDL levels.
AB  - Intravenously infused liposomes may induce cardiopulmonary distress in some human
      subjects, which is a manifestation of "complement activation-related
      pseudoallergy." We have now examined liposome-mediated complement activation in
      human sera with elevated lipoprotein (LDL and HDL) levels, since abnormal or
      racial differences in serum lipid profiles seem to modulate the extent of
      complement activation and associated adverse responses. In accordance with our
      earlier observations, cholesterol-rich (45 mol% cholesterol) liposomes activated
      human complement, as reflected by a significant rise in serum level of S-protein
      bound form of the terminal complex (SC5b-9). However, liposome-induced rise of
      SC5b-9 was significantly suppressed when serum HDL cholesterol levels increased
      by 30%. Increase of serum LDL to levels similar to that observed in heterozygous
      familial hypercholesterolemia also suppressed liposome-mediated SC5b-9 generation
      considerably. While intravenous injection of cholesterol-rich liposomes into pigs
      was associated with an immediate circulatory collapse, the drop in systemic
      arterial pressure following injection of liposomes preincubated with human
      lipoproteins was slow and extended. Therefore, surface-associated lipoprotein
      particles (or apolipoproteins) seem to lessen liposome-induced adverse
      haemodynamic changes, possibly as a consequence of suppressed complement
      activation in vivo. PEGylated liposomes were also capable of activating the human
      complement system, and the presence of surface projected methoxypoly(ethylene
      glycol) chains did not interfere with generation of C3 opsonic fragments. We also
      show that poly(ethylene glycol) is not responsible for PEGylated liposome
      mediated complement activation. The net anionic charge on the phosphate moiety of
      the phospholipid-mPEG conjugate seemed to play a critical role in activation of
      both the classical and alternative pathways of the complement system.

PMID- 16952872
TI  - Pros and cons of the liposome platform in cancer drug targeting.
AB  - Coating of liposomes with polyethylene-glycol (PEG) by incorporation in the
      liposome bilayer of PEG-derivatized lipids results in inhibition of liposome
      uptake by the reticulo-endothelial system and significant prolongation of
      liposome residence time in the blood stream. Parallel developments in drug
      loading technology have improved the efficiency and stability of drug entrapment
      in liposomes, particularly with regard to cationic amphiphiles such as
      anthracyclines. An example of this new generation of liposomes is a formulation
      of pegylated liposomal doxorubicin known as Doxil or Caelyx, whose clinical
      pharmacokinetic profile is characterized by slow plasma clearance and small
      volume of distribution. A hallmark of these long-circulating liposomal drug
      carriers is their enhanced accumulation in tumors. The mechanism underlying this
      passive targeting effect is the phenomenon known as enhanced permeability and
      retention (EPR) which has been described in a broad variety of experimental tumor
      types. Further to the passive targeting effect, the liposome drug delivery
      platform offers the possibility of grafting tumor-specific ligands on the
      liposome membrane for active targeting to tumor cells, and potentially
      intracellular drug delivery. The pros and cons of the liposome platform in cancer
      targeting are discussed vis-a-vis nontargeted drugs, using as an example a
      liposome drug delivery system targeted to the folate receptor.

PMID- 16952873
TI  - Therapeutic application of long-circulating liposomal glucocorticoids in auto
      immune diseases and cancer.
AB  - Glucorticoids are potent drugs that have a multitude of pharmacological actions
      both at genomic and non-genomic levels. Many of the diseases in which
      glucorticoids are routinely administered are featured by angiogenesis and
      enhanced capillary permeability, permitting targeted delivery using long
      circulating drug delivery systems. By encapsulation of glucorticoids in long
      circulating liposomes, drug levels at the site of the pathology are markedly
      higher, increasing and prolonging therapeutic efficacy in models of rheumatoid
      arthritis, multiple sclerosis, and cancer.

PMID- 16952874
TI  - Advanced liposomal vectors as cancer vaccines in melanoma immunotherapy.
AB  - Malignant tumors represent a major source of disability and account for more than
      one of five deaths in Western countries. Among the different cancers, melanoma
      harbors two distinctive features. First, its has long been recognized as an
      immunogenic tumor, and second, an unprecedented rise in incidence is currently
      observed, in face of few therapeutic options. Thus, melanoma represent an ideal
      target for a cancer immunotherapy program. To date, a number of immunodominant
      epitopes from tumor associated antigens (TAA) are used as cancer vaccines in
      clinical trials, in spite of an acknowledged rapid degradation in vivo and low
      immunogenicity. However, most of the immunotherapy trials reported so far do not
      achieve consistent clinical results. Hence, there is an urgent need for the
      development of a carrier system and strong adjuvants suitable for a TAA-based
      cancer immunotherapy. Liposomes and their further development as virosomes with
      added adjuvancy may address both these issues. We report here our experience in
      the tailoring of dedicated advanced liposomal vectors that were developed in the
      context of an upcoming immunotherapy clinical trial for melanoma.

PMID- 16952875
TI  - Liposome-based systems for anti-tumor vaccination: influence of lipopeptide
      adjuvants.
AB  - We have developed liposome-based synthetic constructs incorporating peptide
      epitope(s) (ErbB2 p63-67 CTL which is overexpressed in many tumors and/or HA 307
      319 T-helper) and lipopeptide adjuvants (Pam3CysSerSer, Pam3CysAlaGly) in order
      to elicit an anti-tumor immune response. The epitopes, derivatized with a linker
      containing a cysteine residue, were conjugated on preformed vesicles (dia.
      approximately 100 nm) containing lipopeptides functionalized with thiol reactive
      groups (maleimide or bromoacetyl). The therapeutic efficacy of these constructs
      was evaluated on a Balb/c mice tumor model inoculated with syngenic murine renal
      carcinoma (Renca) cells expressing human ErbB2 (Her2/neu) receptor. A successful
      therapeutic vaccination was obtained which was antigen specific. Furthermore, it
      appeared that the nature of the polar head group of the lipopeptide adjuvant and
      also its type of functionalization influence the efficacy of the construct. In
      our study, the best results were obtained with formulations containing a Pam3CSS
      anchor in association with the CTL and Th epitopes. Considering these promising
      results studies are in progress with a new generation of liposomes that
      incorporate a neutral lipid--lacking adjuvant properties--that serves as anchor
      of the peptide epitopes and new adjuvants synthesized in our laboratory, which
      are screened for their antitumour activity in a therapeutic setting.

PMID- 16952876
TI  - Enhanced liposomal vaccine formulation and performance: simple physicochemical
      and immunological approaches.
AB  - The Dtxd (Diphtheria toxoid) was the first antigen encapsulated within liposomes,
      their adjuvant properties were discovered (their capacity to enhance the vaccine
      immunogenicity). The point here is not to propose a new method to prepare this
      lipossomal vaccine. The central idea is to give new dresses for old vaccines by
      using classical and well-established liposome preparation method changing only
      the encapsulation pH and the immunization protocol. The most appropriate method
      of Dtxd encapsulation within liposome was based on lipid film hydration in 100 mM
      citrate buffer, pH 4.0. This was accompanied by changes on protein
      hydrophobicity, observed by CD and fluorescence spectroscopies. Whenever the Dtxd
      exposed its hydrophobic residues at pH 4.0, it interacted better with the
      lipossomal (observed by electrophoretic mobility) film than when its hydrophobic
      residues were buried (pH 9.0). The Dtxd partition coefficient in Triton-X114 and
      the acrylamide fluorescence quenching were also pH dependent. Both were bigger at
      pH 4.0 than at pH 9.0. The relationship protein structure and lipid interaction
      was pH dependent and now it can be easily maximized to enhance encapsulation of
      antigens in vaccine development. Mice were primed with formulations containing 5
      mug of Dtxd within liposomes prepared in pH 4.0 or 7.0 or 9.0. The boosters were
      done 38 or 138 days after the first immunization. The IgM produced by immediate
      response of all lipossomal formulations were higher than the control (free
      protein). The response patterns and the immune maturity were measured by IgG1 and
      IgG2a titrations. The IgG1 titers produced by both formulations at pH 4.0 and 7.0
      were at least 22 higher than those produced by mice injected lipossomal
      formulation at pH 9.0. When the boosters were done, 138 days after priming the
      mice produced a IgG2a titer of 29 and the group that received the booster 30 days
      after priming produced a titer of 25. The strongest antibody production was the
      neutralizing antibody (245 higher than the control) produced by those mice
      injected with lipossomal formulation at pH 4.0 with the booster done 138 days
      after priming. The simple change on lipossomal pH formulation and timing of the
      booster enhanced both antibody production and selectivity.

PMID- 16952877
TI  - The 'co-delivery' approach to liposomal vaccines: application to the development
      of influenza-A and hepatitis-B vaccine candidates.
AB  - DNA vaccination with mammalian-expressible plasmid DNA encoding protein antigens
      is known to be an effective means to elicit cell-mediated immunity, sometimes in
      the absence of a significant antibody response. This may be contrasted with
      protein vaccination, which gives rise to antibody responses with little evidence
      of cell-mediated immunity. This has led to considerable interest in DNA
      vaccination as a means to elicit cell-mediated immune responses against conserved
      viral antigens or intracellular cancer antigens, for the purpose of therapeutic
      vaccination. However, almost all current vaccines are used prophylactically and
      work by producing antibodies rather than cell mediated immune responses. In the
      present study we have therefore explored the combination of DNA and protein forms
      of an antigen using two exemplary prophylactic vaccine antigens, namely
      inactivated influenza virion and hepatitis-B surface antigen. We studied the
      effects of various combinations of DNA and protein on the antibody response. Co
      administration of soluble forms of DNA and protein representations of the same
      antigen gave rise to the same level of antibody response as if protein were
      administered alone. In contrast, we found that when these antigens are entrapped
      in the same liposomal compartment, that there was a strong synergistic effect on
      the immune response, which was much greater than when either antigen was
      administered alone, or in various other modes of combination (e.g. co
      administration as free entities, also pooled liposomal formulations where the two
      materials were contained in separate liposomal vehicles in the same suspension).
      The synergistic effect of liposomally co-entrapped DNA and protein exceeded,
      markedly, the well known adjuvant effects of plasmid DNA and liposomes. We have
      termed this new approach to vaccination 'co-delivery' and suggest that it may
      derive from the simultaneous presentation of antigen via MHC class-I (DNA) and
      MHC class-II (protein) pathways to CD8+ and CD4+ cells at the same antigen
      presenting cell--a mode of presentation that would commonly occur with live viral
      pathogens. We conclude that co-delivery is a very effective means to generate
      protective antibody responses against viral pathogens.

PMID- 16952878
TI  - Gene transfer by means of lipo- and polyplexes: role of clathrin and caveolae
      mediated endocytosis.
AB  - In this paper we address the contribution of different endocytic pathways to the
      intracellular uptake and processing of differently sized latex particles and of
      plasmid DNA complexes by means of fluorescence microscopy and FACS analysis. By
      using a number of specific inhibitors of either clathrin-dependent or caveolae
      dependent endocytosis we were able to discriminate between these two pathways.
      Latex particles smaller than 200 nm were internalized exclusively by clathrin
      mediated endocytosis, whereas larger particles entered the cells via a caveolae
      dependent pathway.The route of uptake of plasmid DNA complexes appears strongly
      dependent on the nature of the complexes. Thus, lipoplexes containing the
      cationic lipid DOTAP, were exclusively internalized by a clathrin-dependent
      mechanism, while polyplexes prepared from the cationic polymer polyethyleneimine
      (PEI) were internalized in roughly equal proportions by both pathways. Upon
      incubation of cells with lipoplexes containing the luciferase gene abundant
      luciferase expression was observed, which was effectively blocked by inhibitors
      of clathrin-dependent endocytosis but not by inhibitors of the caveolae-dependent
      uptake mechanism. By contrast, luciferase transfection of the cells with
      polyplexes was unaffected by inhibition of clathrin-mediated endocytosis, but was
      nearly completely blocked by inhibitors interfering with the caveolae pathway.
      The results are discussed with respect to possible differences in the mechanism
      by which plasmid DNA is released from lipoplexes and polyplexes into the cytosol
      and to the role of size in the uptake and processing of the complexes. Our data
      suggest that improvement of non-viral gene transfection could very much benefit
      from controlling particle size, which would allow targeting of particle
      internalization via a non-degradative pathway, involving caveolae-mediated
      endocytosis.

PMID- 16952879
TI  - Liposomes and liposome-like vesicles for drug and DNA delivery to mitochondria.
AB  - Mitochondrial research is presently one of the fastest growing disciplines in
      biomedicine. Since the early 1990s, it has become increasingly evident that
      mitochondrial dysfunction contributes to a large variety of human disorders,
      ranging from neurodegenerative and neuromuscular diseases, obesity, and diabetes
      to ischemia-reperfusion injury and cancer. Most remarkably, mitochondria, the
      "power house" of the cell, have also become accepted as the "motor of cell death"
      reflecting their recognized key role during apoptosis. Based on these recent
      exciting developments in mitochondrial research, increasing pharmacological
      efforts have been made leading to the emergence of "Mitochondrial Medicine" as a
      whole new field of biomedical research. The identification of molecular
      mitochondrial drug targets in combination with the development of methods for
      selectively delivering biologically active molecules to the site of mitochondria
      will eventually launch a multitude of new therapies for the treatment of
      mitochondria-related diseases, which are based either on the selective
      protection, repair, or eradication of cells. Yet, while tremendous efforts are
      being undertaken to identify new mitochondrial drugs and drug targets, the
      development of mitochondria-specific drug carrier systems is lagging behind. To
      ensure a high efficiency of current and future mitochondrial therapeutics,
      colloidal vectors, i.e., delivery systems, need to be developed able to
      selectively transport biologically active molecules to and into mitochondria
      within living human cells. Here we review ongoing efforts in our laboratory
      directed toward the development of different phospholipid- and non-phospholipid
      based mitochondriotropic drug carrier systems.

PMID- 16952881
TI  - Elastic vesicles as a tool for dermal and transdermal delivery.
AB  - The main problem in delivery of drugs across the skin is the barrier function of
      the skin, which is located in the outermost layer of the skin, the stratum
      corneum. The stratum corneum consists of corneocytes surrounded by lipid layers,
      the so-called lipid lamellae. When applying drugs onto the skin, the major
      penetration pathway is the tortuous intercellular route along the lipid lamellae.
      In order to increase the number of drugs administered via the transdermal route,
      novel drug delivery systems have to be designed. Among these systems are
      iontophoresis, electroporation, microneedles, and vesicular systems.

PMID- 16952880
TI  - Surfactant therapy for patients with ARDS after cardiac surgery.
AB  - This multicenter study investigated the possibility of reducing mortality rate by
      administering natural lung surfactant additional to standard therapy to treat
      patients after cardiac surgery who developed an acute respiratory failure
      (ARDS/ALI).A total of 78 patients (1998-2002) diagnosed with ALI or ARDS were
      enrolled in the study; patients were considered for study entry only if they
      developed ALI/ARDS within 72 h after cardiac surgery. A total of 36 patients
      (2000-2002) received Surfactant-BL via bronchoscope at a dose of 3 mg/kg twice a
      day, and 42 patients (1998-2000) served as the historical control. Within 24 h
      after the first Surfactant-BL administration the PaO2/FiO2 ratio increased from
      (mean+/-SEM) 129.7+/-9.9 mm Hg to 187.6+/-17.6 mm Hg (p<0.01), FiO2 decreased
      from (mean+/-SEM) 0.71+/-0.03 to 0.56+/-0.03 (p<0.01), and 69.4% of the patients
      treated with surfactant were weaned from the ventilator compared with 50% of the
      control group during a 28-day period. The mortality rate among patients treated
      with Surfactant-BL was 30.6% compared with 50% in the control group. In
      conclusion, early administration of Surfactant-BL leads to the reduction of
      mortality in cardiac patients who develop postoperatively an ALI or ARDS.

PMID- 16952882
TI  - Lipophilic drug transfer between liposomal and biological membranes: what does it
      mean for parenteral and oral drug delivery?
AB  - This review presents the current knowledge on the interaction of lipophilic,
      poorly water soluble drugs with liposomal and biological membranes. The center of
      attention will be on drugs having the potential to dissolve in a lipid membrane
      without perturbing them too much. The degree of interaction is described as
      solubility of a drug in phospholipid membranes and the kinetics of transfer of a
      lipophilic drug between membranes. Finally, the consequences of these two factors
      on the design of lipid-based carriers for oral, as well as parenteral use, for
      lipophilic drugs and lead selection of oral lipophilic drugs is described. Since
      liposomes serve as model-membranes for natural membranes, the assessment of lipid
      solubility and transfer kinetics of lipophilic drug using liposome formulations
      may additionally have predictive value for bioavailability and biodistribution
      and the pharmacokinetics of lipophilic drugs after parenteral as well as oral
      administration.

PMID- 16952883
TI  - Liposome coated stents: a method to deliver drugs to the site of action and
      improve stent blood-compatibility.
AB  - A method to correct stent related complications non-invasively, is the local
      delivery of therapeutic agents. Different drugs have been delivered on stents,
      after being either dispersed or encapsulated in polymeric materials, and placed
      on stents to form drug-eluting-stents (DE-stents). Investigation of possibility
      to cover polymer - coated metallic stents, with liposomal drugs, for preparation
      of novel DE-liposome-coated-stents, has been initiated few years ago. In this
      context our research has been focused on answering the following questions: (i)
      Can liposomes be applied as coatings on polymer covered stents? (ii) Can drug
      release from liposome coated-stents be controlled? And: (iii) how is haemo
      compatibility of stents affected? The results of the experiments carried out
      demonstrate that liposomal formulations of drugs can be used as coating systems
      of polymer covered stents for achieving sustained release of drugs at the site of
      interest. By modifying liposome characteristics, different amounts of drugs may
      be placed on the stents and their release rates can be adjusted for maximum
      therapeutic benefit. Finally, haemocompatibility of stents is highly improved
      (mainly in terms of cell adhesion and activation of coagulation system), when
      stents are coated with heparin-encapsulating -DRV liposomes.

PMID- 16952884
TI  - GMP production of liposomes--a new industrial approach.
AB  - A new scalable liposome production system is presented, which is based on the
      ethanol injection technique. The system permits liposome manufacture regardless
      of production scale, as scale is determined only by free disposable vessel
      volumes. Once the parameters are defined, an easy scale up can be performed by
      just changing the process vessels. These vessels are fully sterilizeable and all
      raw materials are transferred into the sanitized and sterilized system via 0.2
      microm filters to guarantee an aseptic production. Liposome size can be
      controlled by the local lipid concentration at the injection point depending on
      process parameters like injection pressure, lipid concentration and injection
      rate. These defined process parameters are furthermore responsible for highly
      reproducible results with respect to vesicle diameters and encapsulation rates
      Compared to other technologies like the film method which is normally followed by
      size reduction through high pressure homogenization, ultrasonication or
      extrusion, no mechanical forces are needed to generate homogeneous and narrow
      distributed liposomes. Another important advantage of this method is the
      suitability for the entrapment of many different drug substances such as large
      hydrophilic proteins by passive encapsulation, small amphiphilic drugs by a one
      step remote loading technique or membrane association of antigens for vaccination
      approaches.

PMID- 16952885
TI  - Relationship between accuracy and organizational approach on the Rey-Osterrieth
      Complex Figure and the differential ability scales: a pilot investigation.
AB  - The present study was designed as an initial exploration of the relationship
      between global cognitive functioning and organizational and accuracy scores on
      the Rey-Osterrieth Complex Figure (ROCF) in a sample of children and adolescents.
      The relationship between ROCF accuracy scores at Copy and Delay as well as
      Organization and the Differential Ability Scales (DAS) was examined. Results
      indicate moderate correlations between Copy and Delay ROCF scores and various DAS
      indicators of nonverbal problem solving and visuospatial processing. Contrary to
      expectations, organizational scores were not significantly correlated with any of
      the DAS subscales or composite scales. Although further research is needed to
      explore the validity of this organizational scoring scheme with younger patients,
      these findings suggest that organization of the ROCF may be generally unrelated
      to global measures of cognitive ability or may assess processes associated with
      executive functioning untapped by the DAS.

PMID- 16952886
TI  - Memory and executive functions in pediatric chronic kidney disease.
AB  - This study examined the memory and executive functioning of children and
      adolescents with chronic kidney disease (CKD). The sample included 20 children
      and adolescents with CKD ranging in age from 7.50 to 19.04 years (M = 13.41, SD =
      3.20). Intellectual function for the group was within the low average to average
      range (M = 89.32, SD = 14.80). Of the participants with CKD, 12 were receiving
      maintenance dialysis therapy at the time of testing and 8 were managed with
      conservative therapy. Healthy controls were used as a comparison group (n = 18).
      This group ranged in age from 7.47 to 18.37 years (M = 12.93, SD = 2.90).
      Intellectual function was within the average range (M = 112.18, SD = 13.14). All
      subjects received a comprehensive battery of memory and executive function tasks
      as part of a larger neuropsychological evaluation. Preliminary examinations of
      the data revealed a significant difference between the groups in IQ, with the
      typical group being significantly higher than the CKD group. A multivariate
      analysis controlling for chronological age revealed significant group
      differences, with specific differences being noted in all of the memory
      functions, and the Initiation and Sustaining executive function domains. In all
      instances the CKD group performed lower than the typical group. The CKD group was
      particularly deficient in their initiation behaviors within the executive
      function domain. The groups did not differ on Set-Shifting or Inhibition. These
      findings remained present even when IQ and chronological age were controlled in
      the analyses, suggesting the possibility of specific encroachment of renal
      disease on memory and executive functions beyond the generalized effects of lower
      IQ. This study represents one of the most extensive examinations of memory and
      executive functions that has been conducted to date on children and adolescents
      with CKD. While pervasive dysfunction was not apparent in the children with CKD,
      they clearly appeared to be at risk for lower IQ as well as inefficiencies in key
      neurocognitive domains.

PMID- 16952887
TI  - Complex prospective memory in children with ADHD.
AB  - The ability to remember intentions (prospective memory) is fundamental to the
      organization of goal-directed actions in everyday life. Successful prospective
      remembering involves forming, retaining, initiating, and executing an intention.
      Although previous research has demonstrated prospective memory impairments in
      children with attention deficit/hyperactivity disorder (ADHD), this has largely
      focused on the intention initiation and execution stages. In this study, we
      investigate the performance of 20 children with ADHD and 20 matched controls at
      each of the four stages of prospective memory, using a computer multitask
      paradigm. Results suggest that children with ADHD may demonstrate difficulties
      forming delayed intentions, as indicated by impulsive planning, and that this may
      have further implications for the retention and implementation of these delayed
      intentions. While children with ADHD showed comparable multitask switching, this
      appeared to be at the expense of intention execution as they made more
      performance errors than controls. Implications for day-to-day functioning are
      discussed.

PMID- 16952888
TI  - An investigation into the relationship among ADHD symptomatology, creativity, and
      neuropsychological functioning in children.
AB  - This paper examined the relationship between creativity and ADHD symptomatology.
      First, the presence of ADHD symptomatology within a creative sample was explored.
      Secondly, the relationship between cognitive functioning and ADHD symptomatology
      was examined by comparing four groups, aged 10-12 years: 1) 29 ADHD children
      without creativity, 2) 12 creative children with ADHD symptomatology, 3) 18
      creative children without ADHD symptomatology, and 4) 30 controls. Creativity,
      intelligence, processing speed, reaction time, working memory, and inhibitory
      control were measured. Results showed that 40% of the creative children displayed
      clinically elevated levels of ADHD symptomatology, but none met full criteria for
      ADHD. With regard to cognitive functioning, both ADHD and creative children with
      ADHD symptoms had deficits in naming speed, processing speed, and reaction time.
      For all other cognitive measures the creative group with ADHD symptoms
      outperformed the ADHD group. These findings have implications for the development
      and management of creative children.

PMID- 16952889
TI  - Executive functioning predicts social skills following prenatal alcohol exposure.
AB  - Adverse sequelae of prenatal alcohol exposure include executive function and
      social skills impairments, although these two domains have not been empirically
      linked in alcohol-exposed individuals. This study investigated this relationship
      using the BRIEF and the SSRS in 98 children aged 6 to 11 years. Executive
      functions explained a significant percentage of variance in parent and teacher
      rated social skills. No differences were found among children with diagnoses of
      FAS, partial FAS, or alcohol-related neurodevelopmental disorder. It may be
      helpful to consider executive functioning in designing social skills
      interventions for alcohol-exposed children whether or not they have full FAS.

PMID- 16952890
TI  - Neurobehavioral functioning in children with fetal alcohol spectrum disorder.
AB  - Neurobehavioral functioning of 50 Canadian children diagnosed with Fetal Alcohol
      Spectrum Disorder (FASD) was evaluated. The aims of this study were to identify
      specific areas of weakness in neurobehavioral functioning, to examine whether
      neurobehavioral functioning was related to various predictor variables, and to
      determine which measures differentiated between children given a brain score of 2
      (possible dysfunction) and 3 (probable dysfunction). Participants displayed
      difficulties with many aspects of intelligence, memory, executive functioning,
      and attention. Measures of Full scale and Verbal IQ, as well as memory for faces
      and numbers differentiated between children with a brain 2 and 3 ranking. An
      interesting pattern of strengths and weaknesses emerged as well as significant
      differences related to ethnic background, gender, and age. Aboriginal children
      and Caucasian children with FASD do not appear to show the same pattern of
      strengths and weaknesses in neurobehavioral functioning.

PMID- 16952891
TI  - How successful is errorless learning in supporting memory for high and low-level
      knowledge in dementia?
AB  - Errorless learning has been shown to be very successful in the rehabilitation of
      memory problems particularly in patients with severe forms of memory impairment.
      Much of this research has focused on testing knowledge of specific details
      studied, ignoring any additional, higher-level knowledge that patients may have
      acquired during the learning process. Hence, it is pertinent to ask whether
      errorless learning is equally successful in the acquisition of high and low-level
      knowledge. In this paper, we present results of several studies comparing the
      effectiveness of errorless and standard trial-and-error methods in acquisition of
      high and low-level knowledge in people diagnosed with dementia and non-impaired
      controls. In Study 1, participants were asked to learn novel face-name-occupation
      associations; and knowledge across a range of levels, from very general (i.e.,
      high-level) to very specific (i.e., low-level), was examined. For patients with
      probable Alzheimer's disease and controls there was evidence of increased benefit
      from errorless training in general, but the technique was most beneficial for
      patients attempting to retrieve specific detail. Study 2 was conducted to address
      the problem raised by the failure in Study 1 to manipulate learning condition at
      our highest knowledge level. This novel manipulation was successful, but neither
      of the patients received the standard benefit from errorless training. Study 3,
      involving a small group of dementia patients with mixed diagnoses, was conducted
      to replicate findings from Study 1. Results from the group analysis confirmed
      that the benefit obtained from errorless learning increased as a function of
      knowledge specificity, but again several patients failed to show a consistent
      effect of learning condition. Implications for use of the errorless technique are
      discussed.

PMID- 16952892
TI  - Traumatic brain injury and substance misuse: a systematic review of prevalence
      and outcomes research (1994-2004).
AB  - A systematic review of the evidence on substance misuse prevalence in patients
      with traumatic brain injury (TBI) and outcomes associated with this population is
      presented. Building upon an earlier review of the area by Corigan (1995), this
      review is limited to research published between 1994 and 2004. Psycinfo and
      Medline abstract databases were searched for English-language publications citing
      research from Western countries on the epidemiology and outcomes of adult TBI
      patients (aged 15 years or older). The majority of reviewed studies were
      undertaken in the USA and the investigation foci and methods used were
      multifarious, constraining the generalisation of the review findings. Prevalence
      for alcohol intoxication at time of injury in the review was found to be almost
      identical to that in Corrigan's review: 37-51% and 36-51%, respectively. Pre-TBI
      history of alcohol misuse was found to be less prevalent in the present as
      opposed to Corrigan's review: 37-51% and 55-66%, respectively. Outcome findings
      were mixed (also found by Corrigan), but mainly in the expected direction of
      poorer outcomes (neurological, medical, neuropsychological, and functional) in
      patients with pre-TBI substance misuse. Further research and implications for
      services are outlined.

PMID- 16952893
TI  - Patient compliance in brain injury rehabilitation in relation to awareness and
      cognitive and physical improvement.
AB  - The purpose of the present study was to investigate the relationship between
      patients' compliance and awareness and outcome of brain injury rehabilitation.
      Subjects were 98 patients who underwent a holistic neuropsychological outpatient
      rehabilitation programme. Patients had suffered a traumatic brain injury (n =
      26), a cerebrovascular accident (n = 58), or another neurological insult (n =
      14). MEASURES: Two staff members, a neuropsychologist and a physiotherapist,
      retrospectively and separately rated patients' awareness and their compliance.
      Outcome was measured with the d2 test of concentration, measures of oxygen
      uptake, strength endurance, running speed, and patients' and relatives' ratings
      of patients' cognitive, physical, and overall problems on the European Brain
      Injury Questionnaire (EBIQ). The discrepancy between patients' and relatives'
      ratings on the EBIQ was incorporated as a second measure of patients' awareness.
      RESULTS: The neuropsychologist's compliance ratings were significantly related to
      measures of insight, improvement of d2 performance accuracy and stability,
      improvement of oxygen uptake, and reduction of cognitive and overall problems as
      reported by the patients, while the physiotherapist's compliance ratings were
      related to measures of insight, improvement of d2 performance speed, improvement
      of oxygen uptake and strength endurance, and all three EBIQ patient scales.
      DISCUSSION: The results suggest a differential relationship between situation
      specific compliance and outcome.

PMID- 16952894
TI  - An exploration of the experience of gaining awareness of deficit in people who
      have suffered a traumatic brain injury.
AB  - Gaining awareness of deficits was explored in 10 people with moderate to severe
      traumatic brain injury (TBI) using a semi-structured interview and interpretative
      phenomenological analysis. Eight master themes emerged from the transcripts.
      Knowledge of deficits was acquired through personal discovery and the reactions
      of others, often outside the rehabilitation environment. Rehabilitation provided
      explanations and a normalising and supportive environment that facilitated people
      in acknowledging their deficits. Most participants spontaneously referred to
      denial and saw this as an active cognitive and behavioural process that both
      helped and hindered recovery. The emotional reaction to learning about deficits
      was described largely in terms of fear and loss and resonates with psychological
      models of grief.

PMID- 16952896
TI  - Autobiographical memories prompted by automatic thoughts in panic disorder and
      social phobia.
AB  - This study examined the retrieval of autobiographical memories when prompted by
      automatic thoughts that were representative of maladaptive schema content
      specific to 2 anxiety disorders. Participants with panic disorder (n = 20), those
      with social phobia (n = 22) and non-anxious participants (n = 20) indicated the
      first specific memory that came to mind when cued with panic-related, social
      phobia-related and control automatic thoughts. Panic participants retrieved
      memories cued with panic disorder-related automatic thoughts more quickly than
      social phobic and non-anxious participants, and social phobic participants
      retrieved memories cued with social phobia-related automatic thoughts more
      quickly than non-anxious participants. Relative to non-anxious participants,
      participants in both patient groups retrieved more anxious/worried memories when
      cued with automatic thoughts related to their diagnosis and more fearful memories
      when cued with either type of diagnosis-related automatic thought. Results
      indicate that panic and social phobic participants were characterized by general
      threat-relevant autobiographical memory biases.

PMID- 16952897
TI  - Inferential confusion and obsessive beliefs in obsessive-compulsive disorder.
AB  - The goal of the present study was to investigate whether inferential confusion
      could account for the relationships between obsessional beliefs and obsessive
      compulsive disorder (OCD). The Inferential Confusion Questionnaire and the
      Obsessive Beliefs Questionnaire were administered to a sample of 85 participants
      diagnosed with OCD. Results showed that the relationship between obsessive
      beliefs and obsessive-compulsive symptoms decreased considerably when controlling
      for inferential confusion. Conversely, the relationship between inferential
      confusion and obsessive-compulsive symptoms was not substantially affected when
      controlling for obsessive beliefs. Since inferential confusion has an overlap
      with overestimation of threat, a competing hypothesis for the results was
      investigated. Results indicated that inferential confusion was factorially
      distinct from overestimation of threat, and that the independent construct of
      inferential confusion remains significantly related to obsessive-compulsive
      symptoms when controlling for anxious mood. These results are consistent with the
      claim that inferential confusion may be a more critical factor in accounting for
      OCD symptoms than are obsessive beliefs and appraisals.

PMID- 16952898
TI  - Incremental validity of mindfulness-based attention in relation to the concurrent
      prediction of anxiety and depressive symptomatology and perceptions of health.
AB  - This investigation evaluated the role of mindfulness-based attention in
      concurrently predicting anxiety and depressive symptomatology and perceived
      health functioning in a community sample of 170 young adults (95 females; mean
      age (Mage) = 22.2 years, SD = 7.6). Partially consistent with prediction, results
      indicated that, relative to negative and positive affectivity and emotional
      expression and processing associated with approach-oriented coping, mindfulness
      based attention incrementally predicted anhedonic depressive, but not anxious
      arousal, symptoms. Additionally, consistent with prediction, mindfulness-based
      attention demonstrated incremental validity in relation to perceived health, and
      the degree of impairment of health in terms of physical and mental functioning.
      Results are discussed in relation to the construct development of mindfulness
      based attention, and specifically, the role(s) of this factor in emotional and
      physical health processes.

PMID- 16952899
TI  - A first step toward cognitive remediation of voices: a case study.
AB  - Several studies have shown that source-monitoring errors are related to verbal
      hallucinations in schizophrenia. An exploratory pilot study has been carried out
      to investigate the possibility of training patients in how to avoid errors in
      source-monitoring. One patient with paranoid schizophrenia and persistent thought
      insertions was trained for 6 hours to use mnemonic techniques to compensate
      specific deficits in source-monitoring. Results show that the patient was able to
      improve his performance and maintain the acquired progress at a 1-month follow-up
      assessment. These preliminary results are interesting for developing a larger
      controlled study of cognitive remediation of source-monitoring deficits.

PMID- 16952900
TI  - Psychometric properties of the French and English versions of the Vancouver
      Obsessional-Compulsive Inventory and the Symmetry Ordering and Arranging
      Questionnaire.
AB  - The Vancouver Obsessional-Compulsive Inventory (VOCI) and the Symmetry Ordering
      and Arranging Questionnaire (SOAQ) are self-report measures that assess a wide
      variety of symptoms and features of obsessive-compulsive disorder (OCD) including
      checking, contamination, obsessions, hoarding, "just right", indecisiveness, and
      symmetry, ordering and arranging obsessions and compulsions. The original English
      versions of the VOCI and SOAQ have been shown to demonstrate excellent
      psychometric properties. The present study examined the reliability and validity
      of French translations of these measures in a non-clinical sample, and also
      involved the collection of supplementary psychometric information about the
      English versions of the scales from a new sample. Volunteer undergraduate
      students completed questionnaire packages including the VOCI and SOAQ, as well as
      measures of obsessive-compulsive, phobic and depressive symptomatology in their
      native language of either French or English. Results indicate that the French
      versions of the VOCI and SOAQ demonstrate similar and excellent psychometric
      properties to the English versions and that these measures are highly valid and
      reliable assessment tools for use in clinical and research applications in both
      languages.

PMID- 16952901
TI  - Therapists' emotional reactions to patients as a mediator in cognitive
      behavioural treatment of panic disorder with agoraphobia.
AB  - The aims of this study were to examine whether therapists' emotional reactions to
      their patients mediate the effect of personality disorders and interpersonal
      problem behaviours on the outcome of treatment, focusing on an Axis I disorder;
      and whether therapists' reactions mediate the effect of personality disorders on
      the course of interpersonal problems. Therapists completed a checklist of
      emotional reactions to individual patients after the end of residential cognitive
      or guided mastery therapy for 46 inpatients with panic disorder with agoraphobia.
      The severity of DSM-III-R personality disorder was related to therapists'
      insecurity feelings, but not to interest and anger. A higher level of therapists'
      insecurity feelings was related to less reduction in self-reported agoraphobic
      avoidance during treatment, whereas therapists' emotions were unrelated to
      symptomatic course after treatment. Therapists' insecurity feelings appeared
      partly to mediate the relationship between patients' severity of personality
      disorder and persistence of patients' interpersonal dominance and nurturance
      problems.

PMID- 16952903
TI  - Enhancement of renal carcinogenicity by combined inhalation and oral exposures to
      chloroform in male rats.
AB  - Chloroform, ubiquitously present in indoor and outdoor air, drinking water, and
      some foodstuffs, enters the human body by inhalation, oral and dermal routes of
      exposure. In order to provide bioassay data for risk assessment of humans exposed
      to chloroform by multiple routes, effects of combined inhalation and oral
      exposures to chloroform on carcinogenicity and chronic toxicity in male F344 rats
      were examined. A group of 50 male rats was exposed by inhalation to 0 (clean
      air), 25, 50, or 100 ppm (v/v) of chloroform vapor-containing air for 6 h/d and 5
      d/wk during a 104 w period, and each inhalation group was given chloroform
      formulated drinking water (1000 ppm w/w) or vehicle water for 104 wk, ad libitum.
      Renal-cell adenomas and carcinomas and atypical renal-tubule hyperplasias were
      increased in the combined inhalation and oral exposure groups, but not in the
      oral- or inhalation-alone groups. Incidences of cytoplasmic basophilia and
      dilated tubular lumens in the kidney, as well as incidence of positive urinary
      glucose, were markedly increased by the combined exposures, compared with those
      after single-route exposures. It was concluded that combined inhalation and oral
      exposures markedly enhanced carcinogenicity and chronic toxicity in the proximal
      tubule of male rat kidneys, suggesting that carcinogenic and toxic effects of the
      combined exposures on the kidneys were greater than the ones that would be
      expected under an assumption that the two effects of single route exposures
      through inhalation and drinking were additive.

PMID- 16952904
TI  - Genotoxic effects in C57Bl/6J mice chronically exposed to arsenate in drinking
      water and modulation of the effects by low-selenium diet.
AB  - In C57Bl/6J mice chronically exposed to arsenate in drinking water at 50, 200, or
      500 microg As/L, genotoxic effects in bone-marrow cells using micronucleus test
      and in peripheral blood leukocytes using the comet assay were determined after 3,
      6 or 12 mo. To assess the modulating role of selenium in development of the
      effects, the animals were fed a specially prepared low-selenium diet and were
      supplemented with sodium selenite (200 microg Se/L) in drinking water
      (supplemented groups) or were without Se supplementation (nonsupplemented
      groups). Measurements of glutathione peroxidase activity in erythrocytes and
      plasma as well as selenium concentration in plasma were performed after 3, 6, and
      12 mo and showed a marked decrease in values in animals in non-Se supplemented
      compared to Se-supplemented groups. After 3 mo of arsenic exposure in the Se
      supplemented animals the level of DNA fragmentation (without Endo III and Fpg
      enzymes) did not differ from the control; however, increased oxidative damage of
      purine and pyrimidine bases was observed. In groups not supplemented with Se, an
      increase of DNA fragmentation was observed; however, the levels of oxidative DNA
      damage in these groups did not differ from the control. None of the positive
      effects observed in the comet assay after 3 mo was related to arsenate
      concentration. The levels of DNA damage after 6 and 12 mo of exposure to arsenic
      as well as the frequency of micronuclei after 3, 6, and 12 mo did not differ
      significantly between exposed and control animals, irrespective of Se
      supplementation status.

PMID- 16952905
TI  - Pharmacokinetics of triclosan following oral ingestion in humans.
AB  - The number of personal hygiene products containing triclosan has increased
      rapidly during the last decade, and triclosan is one of the most common
      antibacterial compounds used in dentifrices today. However, the extent of
      triclosan exposure has not yet been well described. The potential risks of
      generating triclosan-resistant pathogenic microorganisms or of the selection of
      resistant strains are some areas of concern. The aim of the present study was to
      (1) obtain information on baseline levels of triclosan in plasma and urine, and
      (2) study the pharmacokinetic pattern of triclosan after a single-dose intake.
      Ten healthy volunteers were exposed to a single oral dose of 4 mg triclosan by
      swallowing an oral mouthwash solution. Triclosan in plasma and urine was followed
      before and up to 8 d after exposure. Triclosan levels in plasma increased
      rapidly, with a maximum concentration within 1 to 3 h, and the terminal plasma
      half-life was 21 h. The major fraction was excreted within the first 24 h. The
      accumulated urinary excretion varied between the subjects, with 24 to 83% of the
      oral dose being excreted during the first 4 d after exposure. In conclusion,
      triclosan appears to be readily absorbed from the gastrointestinal tract and has
      a rapid turnover in humans. The high lipid solubility of the substance gives rise
      to questions regarding distribution properties and accumulation. The findings of
      the present study form a basis for greater understanding of the toxicokinetic
      properties of triclosan in humans.

PMID- 16952906
TI  - A comparison of the efficacy of new asymmetric bispyridinium oximes (K027, K048)
      with currently available oximes against tabun by in vivo methods.
AB  - The potency of newly developed asymmetric bispyridinium oximes (K027, K048) in
      reactivating tabun-inhibited acetylcholinesterase (AChE) and in eliminating tabun
      induced acute toxic effects was compared with commonly used oximes (obidoxime,
      trimedoxime, the oxime HI-6) using in vivo methods. Studies determined the
      percent of reactivation of tabun-inhibited blood and tissue AChE in poisoned rats
      and showed that the reactivating efficacy of both newly developed oximes is
      comparable with obidoxime and trimedoxime, the most efficacious known
      reactivators of tabun-inhibited AChE. These were also found to be sufficiently
      efficacious in the elimination of acute lethal toxic effects in tabun-poisoned
      rats. The oxime HI-6, relatively efficacious against soman, did not seem to be an
      adequately effective oxime in reactivation of tabun-inhibited AChE and in
      counteracting acute lethal effects of tabun. In addition, our results confirm
      that the efficacy of oximes in reactivating tabun-inhibited AChE in blood,
      diaphragm, and brain correlates with the potency of oximes in protecting rats
      poisoned with supralethal doses of tabun.

PMID- 16952907
TI  - Comparison of zolpidem and zaleplon exposures in Texas, 1998-2004.
AB  - Zolpidem and zaleplon are used for the treatment of insomnia. The objective of
      this study was to compare the patterns of zolpidem and zaleplon exposures
      reported to Texas poison control centers during 1998-2004. There were 5842 total
      reported zolpidem exposures, of which 2918 (50%) were isolated exposures, and 467
      total reported zaleplon exposures, of which 201 (43%) were isolated exposures.
      Zolpidem patients were 62% male and 67% adult. Zaleplon patients were 67% male
      and 34% adult. The exposure was intentional in 62% of zolpidem and 58% of
      zaleplon exposures. The exposure occurred at the patient's own residence in 94%
      of zolpidem and 97% of zaleplon exposures. Management occurred outside of a
      health care facility for 29% of zolpidem and 32% of zaleplon exposures. The
      medical outcome involved no symptoms due to exposure for 29% of zolpidem and 44%
      of zaleplon exposures, a statistically significant difference. Although many of
      the most frequently reported adverse clinical effects for the two drugs were
      similar (drowsiness, slurred speech, hallucinations, ataxia, tachycardia,
      dizziness, confusion, vomiting), the proportion of exposures with a given adverse
      clinical effect was generally lower for zaleplon. Thus, although zolpidem and
      zaleplon exposures were generally similar with respect to patient gender and age,
      exposure reason and site, and management site, zaleplon exposures were less
      likely to result in minor medical outcomes or manifest as adverse clinical
      effects.

PMID- 16952908
TI  - That awkward age for butterflies: insights from the age of the butterfly
      subfamily Nymphalinae (Lepidoptera: Nymphalidae).
AB  - The study of the historical biogeography of butterflies has been hampered by a
      lack of well-resolved phylogenies and a good estimate of the temporal span over
      which butterflies have evolved. Recently there has been surge of phylogenetic
      hypotheses for various butterfly groups, but estimating ages of divergence is
      still in its infancy for this group of insects. The main problem has been the
      sparse fossil record for butterflies. In this study I have used a surprisingly
      good fossil record for the subfamily Nymphalinae (Lepidoptera: Nymphalidae) to
      estimate the ages of diversification of major lineages using Bayesian relaxed
      clock methods. I have investigated the effects of varying priors on posterior
      estimates in the analyses. For this data set, it is clear that the prior of the
      rate of molecular evolution at the ingroup node had the largest effect on the
      results. Taking this into account, I have been able to arrive at a plausible
      history of lineage splits, which appears to be correlated with known
      paleogeological events. The subfamily appears to have diversified soon after the
      K/T event about 65 million years ago. Several splits are coincident with major
      paleogeological events, such as the connection of the African and Asian
      continents about 21 million years ago and the presence of a peninsula of land
      connecting the current Greater Antilles to the South American continent 35 to 33
      million years ago. My results suggest that the age of Nymphalidae is older than
      the 70 million years speculated to be the age of butterflies as a whole.

PMID- 16952909
TI  - The Akt inhibitor deguelin, is an angiopreventive agent also acting on the NF
      kappaB pathway.
AB  - Several natural compounds, especially plant products and dietary constituents,
      are able to exhibit 'angiopreventive' (anti-angiogenic chemoprevention)
      activities both in vitro and in vivo. Deguelin is a rotenoid of the flavonoid
      family with chemopreventive activities able to decrease tumor incidence in animal
      models for lung, colon, mammary and skin carcinogenesis through Akt inhibition.
      Here we show that deguelin belongs to the 'angiopreventive' molecules and provide
      evidence for molecular events associated with its anti-angiogenic properties. The
      data show that deguelin inhibits HUVE cells growth by inducing cell-cycle arrest
      in the G0/G1 phase and in the absence of apoptosis. Growth arrest is associated
      with induction of p21 and p53 and decreased survivin levels. Deguelin also
      interferes with several points in the angiogenic process, including inhibition of
      endothelial cell migration, invasion and metalloprotease production, and potently
      inhibits in vivo angiogenesis and vascular tumor growth. In addition to Akt, the
      nuclear factor-kappaB (NF-kappaB) kinase pathway, which plays a critical role in
      the regulation of inflammation, vascular homeostasis and angiogenesis, was also
      repressed by deguelin even in the presence of inflammatory stimuli such as tumor
      necrosis factor-alpha (TNF-alpha). These findings reveal a new therapeutic
      potential for deguelin in angioprevention and anti-angiogenic therapy.

PMID- 16952910
TI  - Compensatory mammary growth following protein restriction during pregnancy and
      lactation increases early-onset mammary tumor incidence in rats.
AB  - Breast cancer incidence is increased in women with both high and low birth
      weight. The latter is also associated with hyperglycaemia, insulin resistance and
      type-2 diabetes, each of which independently increases breast cancer risk. We
      showed previously in our model of poor early-growth that pregnancy estradiol
      levels were raised while offspring developed type-2 diabetes. We hypothesized
      that nutritionally-induced poor early-growth influences breast cancer risk and
      investigated this in our model. Wistar rat dams were given either a control diet
      (20% casein) or an isocaloric low-protein (LP) diet (8% casein) throughout
      pregnancy and lactation. Offspring postnatal mammary gland development was
      assessed by morphometry. To identify potential growth mechanisms, we measured
      protein expression of receptors involved in insulin and hormone signaling, both
      in cleared mammary gland lysates and isolated epithelial cells. Mammary tumor
      incidence and latency (n=96) was monitored after three weekly intraperitoneal
      nitrosomethylurea injections (50 mg/kg body wt). LP offspring displayed reduced
      postnatal ductal branching and epithelial invasion at 3 weeks, followed by
      compensatory mammary growth 1 week later coinciding with increased protein
      expression of receptors to insulin, IGF-1 and estrogen. Significantly, early
      mammary tumor incidence (0-16 weeks post-treatment) was doubled in LP offspring
      [RR, 2.13 (1.02, 4.45); P=0.046]. The data suggest that poor early nutrition has
      an important influence on the mammary primordium, and increases future
      susceptibility to breast cancer. Up-regulated growth factor and hormone signaling
      during compensatory mammary growth may mediate this increased susceptibility and
      present potential targets for intervention.

PMID- 16952911
TI  - Comprehensive DNA methylation profiling in a human cancer genome identifies novel
      epigenetic targets.
AB  - Using a unique microarray platform for cytosine methylation profiling, the DNA
      methylation landscape of the human genome was monitored at more than 21,000
      sites, including 79% of the annotated transcriptional start sites (TSS). Analysis
      of an oligodendroglioma derived cell line LN-18 revealed more than 4000
      methylated TSS. The gene-centric analysis indicated a complex pattern of DNA
      methylation exists along each autosome, with a trend of increasing density
      approaching the telomeres. Remarkably, 2% of CpG islands (CGI) were densely
      methylated, and 17% had significant levels of 5 mC, whether or not they
      corresponded to a TSS. Substantial independent verification, obtained from 95
      loci, suggested that this approach is capable of large scale detection of
      cytosine methylation with an accuracy approaching 90%. In addition, we detected
      large genomic domains that are also susceptible to DNA methylation reinforced
      inactivation, such as the HOX cluster on chromosome 7 (CH7). Extrapolation from
      the data suggests that more than 2000 genomic loci may be susceptible to
      methylation and associated inactivation, and most have yet to be identified.
      Finally, we report six new targets of epigenetic inactivation (IRX3, WNT10A,
      WNT6, RARalpha, BMP7 and ZGPAT). These targets displayed cell line and tumor
      specific differential methylation when compared with normal brain samples,
      suggesting they may have utility as biomarkers. Uniquely, hypermethylation of the
      CGI within an IRX3 exon was correlated with over-expression of IRX3 in tumor
      tissues and cell lines relative to normal brain samples.

PMID- 16952912
TI  - Chemoprevention of rat prostate carcinogenesis by dietary 16alpha-fluoro-5
      androsten-17-one (fluasterone), a minimally androgenic analog of
      dehydroepiandrosterone.
AB  - Dehydroepiandrosterone (DHEA) is a potent inhibitor of prostate carcinogenesis in
      rats. However, concerns related to the possible androgenicity of DHEA may
      preclude its use for chemoprevention of human prostate cancer. Studies were
      performed to compare the androgenicity of DHEA and a fluorinated DHEA analog,
      16alpha-fluoro-5-androsten-17-one (fluasterone), and to determine the
      chemopreventive activity of fluasterone in the rat prostate. Comparisons of
      accessory sex gland weight and histology in gonadectomized male rats demonstrated
      that fluasterone is less androgenic than is DHEA. Fluasterone conferred
      significant protection against prostate carcinogenesis induced in Wistar-Unilever
      rats by a sequential regimen of N-methyl-N-nitrosourea+testosterone. Chronic
      administration of fluasterone at levels of 2000 and 1000 mg/kg diet reduced the
      incidence of adenocarcinoma in the dorsolateral/anterior prostate from 64% in
      dietary controls to 28 and 31%, respectively. Other than a dose-related
      suppression of body weight gain, chronic exposure to fluasterone induced no
      clinical evidence of toxicity; suppression of body weight gain may be either a
      pharmacological effect or a minimally toxic effect of the compound. These data
      demonstrate that a minimally androgenic analog of DHEA protects against prostate
      carcinogenesis induced in rats by a chemical carcinogen + androgen. The reduced
      androgenicity of fluasterone may obviate toxicities associated with the
      androgenicity of the parent compound. On this basis, fluasterone merits
      consideration for evaluation in clinical trials for prostate cancer prevention.
      The chemopreventive activity of a non-androgenic DHEA analog suggests that at
      least a portion of the chemopreventive activity of DHEA in the rat prostate is
      unrelated to hormonal effects.

PMID- 16952913
TI  - Prevention of experimental colitis by parenteral administration of a pathogen
      derived immunomodulatory molecule.
AB  - BACKGROUND: Filamentous haemagglutinin (FHA) of Bordetella pertussis subverts
      host immune responses by inhibiting interleukin (IL)12 and enhancing IL10
      production by macrophages and dendritic cells, and promoting the induction of
      regulatory T cells. HYPOTHESIS: Injection of FHA would ameliorate disease in a T
      cell-dependent model of colitis via the induction of anti-inflammatory cytokines
      and regulatory T cells. METHODS: Colitis was induced by injection of
      CD4CD45RB(high) naive T cells into severe combined immunodeficient (SCID) mice.
      Mice were treated with four subcutaneous injections of FHA or buffer alone.
      RESULTS: Parenteral injection of FHA stimulated IL10 and/or transforming growth
      factor beta production in local and mesenteric lymph nodes and Peyer's patches of
      mice 2-6 h after administration. Compared with phosphate-buffered saline-treated
      mice, FHA-treated SCID mice had significantly (p<0.01) less weight loss, lower
      colon weight, less colon shrinkage and reduced inflammatory lesions. The
      therapeutic effect of FHA was associated with enhanced IL10 and reduced type 1
      and type 2 T helper cytokine production by spleen cells. Finally, FHA also
      attenuated the symptoms of colitis in SCID mice transferred with CD4CD45RB(high)
      T cells from IL10-deficient mice. CONCLUSIONS: Our finding shows that FHA
      suppresses type 1 T helper and pro-inflammatory cytokines, and ameliorates
      disease activity in a chronic T cell-dependent model of colitis, an effect that
      was not dependent on IL10 production by T cells, but was associated with
      induction of anti-inflammatory cytokines in vivo. Having already been used as a
      pertussis vaccine component in children, FHA is a promising candidate for
      clinical testing in patients with Crohn's disease.

PMID- 16952914
TI  - Influence of cognitive impairment on the institutionalisation rate 3 years after
      a stroke.
AB  - BACKGROUND AND PURPOSE: Pre-existing cognitive decline and new-onset dementia are
      common in patients with stroke, but their influence on institutionalisation rates
      is unknown. OBJECTIVE: To evaluate the influence of cognitive impairment on the
      institutionalisation rate 3 years after a stroke. DESIGN: (1) The previous
      cognitive state of 192 consecutive patients with stroke living at home before the
      stroke (with the Informant Questionnaire on COgnitive Decline in the Elderly
      (IQCODE)), (2) new-onset dementia occurring within 3 years and (3)
      institutionalisation rates within 3 years in the 165 patients who were discharged
      alive after the acute stage were prospectively evaluated. RESULTS: Independent
      predictors of institutionalisation over a 3-year period that were available at
      admission were age (adjusted odds ratio (adjOR) for 1-year increase = 1.08; 95%
      confidence interval (CI) 1.03 to 1.15), severity of the neurological deficit
      (adjOR for 1-point increase in Orgogozo score = 0.97; 95% CI 0.96 to 0.99) and
      severity of cognitive impairment (adjOR for 1-point increase in IQCODE score =
      1.03; 95% CI 1 to 1.06). Factors associated with institutionalisation at 3 years
      that were present at admission or occurred during the follow-up were age (adjOR
      for 1-year increase = 1.17; 95% CI 1.07 to 1.27) and any (pre-existing or new)
      dementia (adjOR = 5.85; 95% CI 1.59 to 21.59), but not the severity of the
      deficit of the neurological deficit. CONCLUSION: Age and cognitive impairment are
      more important predictors of institutionalisation 3 years after a stroke than the
      severity of the physical disability.

PMID- 16952915
TI  - Temporal sensitivity in a hemianopic visual field can be improved by long-term
      training using flicker stimulation.
AB  - BACKGROUND: Blindness of a visual half-field (hemianopia) is a common symptom
      after postchiasmatic cerebral lesions. Although hemianopia severely limits
      activities of daily life, current clinical practice comprises no training of
      visual functions in the blind hemifield. OBJECTIVE: To find out whether flicker
      sensitivity in the blind hemifield can be improved with intensive training, and
      whether training with flicker stimulation can evoke changes in cortical
      responsiveness. METHODS: Two men with homonymous hemianopia participated in the
      experiments. They trained with flicker stimuli at 30 degrees or with flickering
      letters at 10 degrees eccentricity twice a week for a year, and continued
      training with more peripheral stimuli thereafter. Neuromagnetic responses were
      registered at 1-2-month intervals, and the Goldmann perimetry was recorded
      before, during and after training. RESULTS: Flicker sensitivity in the blind
      hemifield improved to the level of the intact hemifield within 30 degrees
      eccentricity in one participant and 20 degrees eccentricity in the other.
      Flickering letters were recognised equally at 10 degrees eccentricity in the
      blind and intact hemifields. Improvement spread from the stimulated horizontal
      meridian to the whole hemianopic field within 30 degrees. Before training,
      neuromagnetic recordings showed no signal above the noise level in the hemianopic
      side. During training, evoked fields emerged in both participants. No changes
      were found in the Goldmann perimetry. DISCUSSION: Results show that sensitivity
      to flicker could be fully restored in the stimulated region, that improvement in
      sensitivity spreads to the surrounding neuronal networks, and that, during
      training, accompanying changes occurred in the neuromagnetic fields.

PMID- 16952916
TI  - Compensatory cortical activation during performance of an attention task by
      patients with diffuse axonal injury: a functional magnetic resonance imaging
      study.
AB  - OBJECTIVE: To determine how cortical compensation occurs in higher cognitive
      systems during the recovery phase of diffuse axonal injury (DAI). DESIGN: 12
      right-handed patients with a magnetic resonance imaging (MRI) lesion pattern
      compatible with pure DAI were identified. Pure DAI was defined as finding of
      traumatic microbleeds on T2*-weighted gradient-echo images in the absence of
      otherwise traumatic or non-traumatic MRI abnormalities. 12 matched healthy
      controls were also enrolled. Functional magnetic resonance imaging (fMRI) was
      used to assess brain activation during a working memory test (Paced Visual Serial
      Attention Test (PVSAT)). RESULTS: No significant group differences were observed
      in reaction times for the PVSAT. Although patients with pure DAI committed a few
      errors during the PVSAT, controls respond correctly to each probe. Controls
      showed activations in the left frontal gyrus, left parietal gyrus and right
      inferior parietal gyrus. Patients with pure DAI showed activations in the left
      inferior frontal gyrus, right inferior frontal gyrus and right middle frontal
      gyrus. Between-group analysis of the PVSAT task showed significantly greater
      activation of the right inferior frontal gyrus (BA 45) and right middle frontal
      gyrus (BA 9) in patient with pure DAI versus controls. CONCLUSIONS: Patients with
      pure DAI require compensatory activation of the contralateral (right) prefrontal
      region to carry out activities similar to healthy controls. These findings
      provide further evidence for the adaptive capacity of neuronal systems and brain
      plasticity during the recovery stages of DAI.

PMID- 16952917
TI  - Effect of levodopa on cognitive function in Parkinson's disease with and without
      dementia and dementia with Lewy bodies.
AB  - BACKGROUND: Levodopa (L-dopa) is the gold standard treatment for Parkinson's
      disease, but a lack of clear efficacy combined with a perceived liability to
      neuropsychiatric side effects has limited L-dopa use in patients with
      parkinsonism and dementia. Therefore, the effect of L-dopa on the cognitive
      profile of dementia with Lewy bodies (DLB) and Parkinson's disease with dementia
      (PDD) is unclear. AIM: To ascertain the acute and long-term effects of L-dopa on
      aspects of attention and cognition in patients with DLB and PDD, and to compare
      these with the effects in Parkinson's disease. METHOD: Baseline cognitive and
      motor function was assessed off L-dopa in patients with Parkinson's disease (n =
      22), PDD (n = 27) and DLB (n = 11) using standard "bedside" measures and a
      computerised programme detecting reaction times and accuracy. All patients then
      underwent an acute L-dopa challenge with subsequent subjective and objective
      analysis of alertness, verbal recall, reaction times and accuracy. The same
      parameters were measured after 3 months on L-dopa to assess the prolonged effect.
      RESULTS: Acute L-dopa challenge considerably improved motor function and
      subjective alertness in all patients without compromising either reaction times
      or accuracy, but increased fluctuations were noted in both groups with dementia.
      Neuropsychiatric scores improved in patients with Parkinson's disease both with
      and without dementia on L-dopa at 3 months. Although patients with Parkinson's
      disease also had better mean global cognitive function at this time, mean verbal
      attention and memory deteriorated, and patients with PDD had slower reaction
      times in some tests. No patient had a marked deterioration over this time.
      Patients with DLB did not experience any adverse cognitive or neuropsychiatric
      effects after 3 months of L-dopa treatment. CONCLUSION: The use of L-dopa in
      patients with parkinsonism with dementia does not adversely affect cognitive
      function.

PMID- 16952918
TI  - Comparison of the effects of thoracic epidural analgesia and i.v. infusion with
      lidocaine on cytokine response, postoperative pain and bowel function in patients
      undergoing colonic surgery.
AB  - BACKGROUND: Both thoracic epidural analgesia (TEA) and i.v. lidocaine were able
      to decrease postoperative pain and duration of ileus. We compared TEA and i.v.
      lidocaine (IV) regarding their effects on cytokines, pain and bowel function
      after colonic surgery. METHODS: Sixty patients were randomly allocated to one of
      the three groups. TEA group had lidocaine 2 mg kg(-1) followed by 3 mg kg(-1) h(
      1) epidurally and an equal volume of i.v. normal saline. The IV group received
      the same amount of lidocaine i.v. and normal saline epidurally. The control group
      received normal saline via both routes. These regimens were started 30 min before
      surgery and were continued throughout. Blood cytokines were measured at scheduled
      times within 72 h. RESULTS: Both TEA and IV groups had better pain relief. The
      total consumptions using patient-controlled epidural analgesia were 81.6 (6.5),
      55.0 (5.3) and 45.6 (3.9) ml (P<0.01) and the times of flatus passage were 50.2
      (4.9), 60.2 (5.8) and 71.7 (4.7) h (P<0.01) in the TEA, IV and control groups,
      respectively. The TEA group exhibited the best postoperative pain relief and the
      least cytokine surge. The IV group experienced better pain relief and less
      cytokine release than the control group. CONCLUSIONS: The TEA lidocaine had
      better pain relief, lower opioid consumption, earlier return of bowel function
      and lesser production of cytokines than IV lidocaine during 72 h after colonic
      surgery; IV group was better than the control group.

PMID- 16952919
TI  - Air pollution: To the heart of the matter.

PMID- 16952920
TI  - Lipoprotein-associated phospholipase A2 activity and risk of heart failure: The
      Rotterdam study.
AB  - AIMS: Evidence is accumulating that inflammation plays a role in the
      pathophysiology of heart failure. Lipoprotein-associated phospholipase A2 (Lp
      PLA2) has pro-inflammatory properties. We investigated whether Lp-PLA2 activity
      is associated with heart failure. METHODS AND RESULTS: Lp-PLA2 activity was
      determined in a random sample of 1820 subjects from the Rotterdam Study, a
      population-based cohort study among persons aged 55 years and over. During a mean
      follow-up of 6.7 years, 94 heart failure cases occurred. We excluded participants
      with heart failure or coronary heart disease at baseline and we accounted for
      incident coronary heart disease during follow-up. We used Cox proportional hazard
      models to compute hazard ratios adjusted for age, sex, non-HDL cholesterol, HDL
      cholesterol, body mass index, systolic blood pressure, diastolic blood pressure,
      hypertension, diabetes mellitus, smoking, and C-reactive protein. The hazard
      ratio per unit increase of Lp-PLA2 activity was 1.03 [95% confidence interval
      (95% CI 1.01-1.05]; P for trend was 0.011. Hazard ratios for the second, third,
      and fourth quartiles were 1.06 (95% CI 0.55-2.04), 1.43 (95% CI 0.73-2.81), and
      2.33 (95% CI 1.21-4.49), respectively, using the lowest quartile of Lp-PLA2
      activity as the reference category. CONCLUSION: This study suggests that Lp-PLA2
      activity is independently associated with incident heart failure.

PMID- 16952921
TI  - The diagnostic utility of N-terminal pro-B-type natriuretic peptide for the
      detection of major structural heart disease in patients with atrial fibrillation.
AB  - AIMS: To assess the role of N-terminal pro-B-type natriuretic peptide (NT-proBNP)
      in the diagnosis of major structural heart disease (MSHD) in patients with atrial
      fibrillation (AF) compared with those with sinus rhythm (SR) using receiver
      operator characteristic (ROC) analysis. NT-proBNP is elevated in MSHD and heart
      failure (HF). AF, a common finding in HF and MSHD, is also associated with raised
      plasma NT-proBNP. As a result, the utility of NT-proBNP for predicting MSHD may
      be reduced. METHODS AND RESULTS: One thousand four hundred and seventy-six
      patients underwent assessment at a single centre, performed without the knowledge
      of NT-proBNP levels. MSHD included left ventricular (LV) systolic and diastolic
      dysfunctions, left-sided valvular disease, right heart disease (including
      pulmonary hypertension) and severe LV hypertrophy. One hundred and fifty-five
      patients were excluded due to renal impairment, atrial flutter, or a pacemaker.
      Seven hundred and ninety-three patients were diagnosed with MSHD. Median NT
      proBNP concentrations for patients with MSHD were 960 (IQR 359-2625) pg/mL and
      2491 (1443-4368) pg/mL for SR (n = 591) and AF (n = 202), respectively (P <
      0.001). Patients without MSHD had NT-proBNP levels of 179 (90-401) pg/mL and 1000
      (659-1760) pg/mL for SR (n = 454) and AF (n = 74), respectively (P < 0.001). The
      area under the ROC curve for NT-proBNP to detect MSHD was 0.79 for SR (95% CI
      0.77-0.82) and 0.78 for AF (95% CI 0.72-0.84). NT-proBNP cut-off levels necessary
      to achieve a 1 in 100 false negative rate were 27.5 (7.5-30.5) pg/ml and 524 (253
      662) pg/ml for SR and AF, respectively. CONCLUSION: NT-proBNP performs as well in
      patients with SR as in those with AF. However, significantly higher cut-off
      levels are required for patients with AF to achieve similar levels of diagnostic
      specificity.

PMID- 16952922
TI  - A prospective study on spontaneous fluctuations between diagnostic and non
      diagnostic ECGs in Brugada syndrome: implications for correct phenotyping and
      risk stratification.
AB  - AIMS: Fluctuations between the diagnostic ECG pattern and non-diagnostic ECGs in
      patients with Brugada syndrome are known, but systematic studies are lacking. The
      purpose of this study was to prospectively evaluate the spontaneous ECG changes
      between diagnostic and non-diagnostic ECG patterns in patients diagnosed with
      Brugada syndrome. METHODS AND RESULTS: In 43 patients with Brugada syndrome (27
      males; mean age 45+/-11 years), 310 resting ECGs were obtained during a median
      follow-up of 17.7 months. The ECGs were analysed for the presence of coved type,
      saddle-back type or no, respectively unspecific, changes. A coved-type ECG
      pattern with more than 2 mm ST-segment elevation in at least two right precordial
      leads was defined as diagnostic. The patients were compared for different
      clinical characteristics with respect to the pattern of fluctuations. Out of a
      total of 310 ECGs, 102 (33%) revealed a coved type, 91 (29%) a saddle-back type,
      and 117 (38%) a normal ECG. Fifteen patients (35%) initially presented with a
      diagnostic coved-type ECG. Fourteen patients (33%) with an initially coved-type
      ECG exhibited intermittently non-diagnostic ECGs during follow-up. Only one
      patient (2%) presented constantly with a coved-type ECG. Out of 28 patients (65%)
      with an initially non-diagnostic ECG, eight (19%) patients developed a diagnostic
      coved-type ECG during follow-up. Twenty patients (47%) revealed a coved-type ECG
      during ajmaline challenge, but never had a baseline coved-type ECG recorded. No
      significant differences were found in gender and clinical characteristics among
      patients with or without fluctuations between diagnostic and non-diagnostic basal
      ECGs. The rate of inducible ventricular fibrillation was significantly higher in
      patients with more than 50% coved-type ECGs than in patients with less than 50%
      diagnostic ECGs. CONCLUSION: The prevalence of fluctuations between diagnostic
      and non-diagnostic ECGs in patients with Brugada syndrome is high and may have an
      implication on the correct phenotyping and on the risk stratification in patients
      with Brugada syndrome without aborted sudden cardiac death. For correct
      phenotyping and risk stratification, repetitive ECG recordings seem to be
      mandatory.

PMID- 16952923
TI  - Patterns of restenosis after drug-eluting stent implantation: Insights from a
      contemporary and comparative analysis of sirolimus- and paclitaxel-eluting
      stents.
AB  - AIM: To evaluate patterns of restenosis following implantation of sirolimus
      eluting stent (SES) and paclitaxel-eluting stent (PES) in comparable unselected
      lesions. METHODS AND RESULTS: We have identified all episodes of restenosis after
      SES or PES implantation in our institutions between March 2003 and March 2005.
      Restenosis pattern was classified as focal, diffuse, proliferative, or occlusive.
      The position of focal restenosis was also categorized as proximal, in-stent,
      distal, or multi-focal. We have characterized 150 and 149 restenotic lesions in
      SES and PES groups, respectively. The incidence of diffuse and occlusive
      restenosis was significantly higher in PES than in SES (47.6 vs. 27.0%, P <
      0.001). Multivariable (OR 2.693, 95% CI 1.425-5.089, P = 0.002) and propensity
      (OR 3.00, 95% CI 1.584-5.672, P < 0.001) analyses confirmed the positive
      association of PES with non-focal restenosis. For both stents, focal-edge
      restenosis was significantly more likely to occur proximally than distally (61.0
      vs. 16.9%, P < 0.001 for PES and 45.8 vs. 16.8%, P < 0.001 for SES). CONCLUSION:
      Focal restenosis remains the most common pattern with SES. In contrast, just
      under half of restenosis in PES is the more severe non-focal pattern.
      Paradoxically, the majority of focal restenosis occurs at the proximal stent
      margin for both platforms.

PMID- 16952924
TI  - Periaortitis complicating chronic aortic dissection.

PMID- 16952925
TI  - Association of ankle-brachial index and plaques in the carotid and femoral
      arteries with cardiovascular events and total mortality in a population-based
      study with 13 years of follow-up.
AB  - AIMS: Peripheral arterial occlusive disease is associated with a high risk of
      cardiovascular morbidity and mortality. We prospectively examined the association
      of the ankle-brachial index (ABI) and arterial plaques in carotid and femoral
      arteries with incident myocardial infarctions (MIs) and cardiovascular and total
      mortality in 1325 participants of the population-based MONICA Augsburg Survey
      1989/90. METHODS AND RESULTS: At baseline, 6.1% of men and 2.6% of women had an
      ABI < or =0.9. At least one plaque in the carotid or femoral arteries was
      identified in 51.8% of men and 36.3% of women. During a 13-year follow-up, 58
      persons (4.4%) suffered a MI before age 75 and 189 persons (14.3%) died, 86
      (6.5%) of them from cardiovascular causes. Kaplan-Meier curves confirmed both
      measurements as strong predictors for all three endpoints (P<0.0001). Cox
      regression analysis revealed an increase of the risk for MI and cardiovascular
      and total mortality of 22 (P=0.012), 35, and 32% (P<0.00001), respectively, per
      0.1 unit decrease in ABI. Correction for measurement error in ABI increased these
      estimates. The increase in risk for MI and cardiovascular and total mortality was
      52, 70, and 45%, respectively, for each increase in the number of plaque-affected
      arteries (P<0.0001). CONCLUSION: Both ABI and number of plaque-affected arteries
      are strong predictors for incident MI and cardiovascular and total mortality.

PMID- 16952926
TI  - Risk factors for primary ventricular fibrillation during acute myocardial
      infarction: a systematic review and meta-analysis.
AB  - AIMS: To evaluate potential risk factors for primary ventricular fibrillation
      (PVF) during acute myocardial infarction (AMI) by a systematic review and meta
      analyses. METHODS AND RESULTS: We searched PubMed for English articles on
      'humans' published between 1964 and January 2006 using a validated combination of
      MESH terms. Twenty-one cohort studies describing 57 158 patients with AMI were
      analysed. Patients with validated PVF (n=2316) were characterized by an earlier
      admission (weighted mean difference -2.62 h), male gender [odds ratio (OR 1.27)],
      smoking (OR 1.26), absence of history of angina (OR for history of angina 0.84),
      lower heart rate at admission (weighted mean difference -4.02 b.p.m.), ST-segment
      elevation on admission ECG (OR 3.35), AV conduction block before PVF (OR 2.02),
      and lower serum potassium at admission (weighted mean difference -0.27 meq/L).
      Patients with validated PVF developed a larger enzymatic infarct size
      (standardized mean difference 0.74, P<0.00001). PVF was not associated with a
      history of myocardial infarction or hypertension. CONCLUSION: Patients who
      developed a validated PVF presented with characteristics of both abrupt coronary
      occlusion and early hospital admission. This review provides no evidence for risk
      factors for PVF other than ST-elevation and time from onset of symptoms. To find
      new risk factors, studies should compare validated PVF patients with non-PVF
      patients who have no signs of heart failure and comparable time delay between
      onset of symptoms and medical attendance.

PMID- 16952927
TI  - Short QT syndrome and arrhythmogenic cardiac diseases in the young: the challenge
      of implantable cardioverter-defibrillator therapy for children.

PMID- 16952928
TI  - Re: "Cigarette smoking and incidence of first depressive episode: An 11-year,
      population-based follow-up study".

PMID- 16952929
TI  - Metabolic syndrome predicts prostate cancer in a cohort of middle-aged Norwegian
      men followed for 27 years.
AB  - The aim of the study was to establish whether metabolic syndrome predicts the
      incidence of prostate cancer. The hypothesis was tested using the 27-year follow
      up of the prospective cohort of 16,209 men aged 40-49 years who participated in
      the Oslo Study in 1972-1973. Men with established diabetes and men with cancer
      diagnosed before screening were excluded, leaving 15,933 for analyses. Metabolic
      syndrome is here composed of body mass index, nonfasting glucose, triglycerides,
      and blood pressure or drug-treated hypertension. Two analytical approaches were
      compared, namely, predefined (adjusted from National Cholesterol Education
      Program) and quartile values of risk factors. Age, body mass index, and sedentary
      versus intermediate physical activity at work were significant predictors in
      univariate proportional hazards regression analyses. Combinations of any two
      (relative risk = 1.23; p = 0.04) or any three (relative risk = 1.56; p = 0.00)
      factors of the metabolic syndrome using quartile values of risk factors were
      predictive of prostate cancer. The number of cases for four factors was too small
      for analyses. Predefined values of the risk factors were not found to be
      predictive. In conclusion, metabolic syndrome was found to predict prostate
      cancer during 27 years of follow-up, indicating an association between insulin
      resistance and the incidence of prostate cancer.

PMID- 16952930
TI  - Invited commentary: evaluation of measures of urinary albumin excretion in
      epidemiologic studies.

PMID- 16952931
TI  - Re: "Cigarette smoking and incidence of first depressive episode: An 11-year,
      population-based follow-up study".

PMID- 16952932
TI  - A study of technical signs in science: implications for lexical database
      development.
AB  - Both classroom instruction and lexical database development stand to benefit from
      applied research on sign language, which takes into consideration American Sign
      Language rules, pedagogical issues, and teacher characteristics. In this study of
      technical science signs, teachers' experience with signing and, especially,
      knowledge of content, were found to be essential for the identification of signs
      appropriate for instruction. The results of this study also indicate a need for a
      systematic approach to examine both sign selection and its impact on learning by
      deaf students. Recommendations are made for the development of lexical databases
      and areas of research for optimizing the use of sign language in instruction.

PMID- 16952933
TI  - In vitro dosing of cells with poorly soluble particles.

PMID- 16952934
TI  - Characterization of Stg fimbriae from an avian pathogenic Escherichia coli
      O78:K80 strain and assessment of their contribution to colonization of the
      chicken respiratory tract.
AB  - In a previous study, ecs-3, a sequence from avian pathogenic Escherichia coli
      (APEC) O78:K80 strain chi7122, was found to be expressed in vivo in infected
      chicken tissues. The region encompassing ecs-3 carries a fimbrial gene cluster
      that is a putative ortholog of the stg fimbrial gene cluster of Salmonella
      enterica serovar Typhi. This APEC fimbrial gene cluster, which we have termed
      stg, is a member of a distinct group of related fimbriae that are located in the
      glmS-pstS intergenic region of certain E. coli and S. enterica strains. Under the
      control of the pBAD promoter, the production of Stg fimbriae was demonstrated by
      Western blotting and immunogold electron microscopy with E. coli K-12.
      Transcriptional fusions suggest that stg expression is influenced by the
      carbohydrate source and decreased by the addition of iron and that Fur plays a
      role in the regulation of stg expression. stg sequences were associated with APEC
      O78 isolates, and stg was phylogenetically distributed among E. coli reference
      strains and clinical isolates from human urinary tract infections. Stg fimbriae
      contributed to the adherence of a nonfimbriated E. coli K-12 strain to avian lung
      sections and human epithelial cells in vitro. Coinfection experiments with APEC
      strain chi7122 and an isogenic Deltastg mutant demonstrated that compared to the
      wild-type parent, the Deltastg mutant was less able to colonize air sacs, equally
      able to colonize lungs, and able to more effectively colonize tracheas of
      infected chickens. Stg fimbriae, together with other adhesins, may therefore
      contribute to the colonization of avian respiratory tissues by certain APEC
      strains.

PMID- 16952935
TI  - Properties of succinyl-coenzyme A:D-citramalate coenzyme A transferase and its
      role in the autotrophic 3-hydroxypropionate cycle of Chloroflexus aurantiacus.
AB  - The phototrophic bacterium Chloroflexus aurantiacus uses the 3-hydroxypropionate
      cycle for autotrophic CO(2) fixation. This cycle starts with acetyl-coenzyme A
      (CoA) and produces glyoxylate. Glyoxylate is an unconventional cell carbon
      precursor that needs special enzymes for assimilation. Glyoxylate is combined
      with propionyl-CoA to beta-methylmalyl-CoA, which is converted to citramalate.
      Cell extracts catalyzed the succinyl-CoA-dependent conversion of citramalate to
      acetyl-CoA and pyruvate, the central cell carbon precursor. This reaction is due
      to the combined action of enzymes that were upregulated during autotrophic
      growth, a coenzyme A transferase with the use of succinyl-CoA as the CoA donor
      and a lyase cleaving citramalyl-CoA to acetyl-CoA and pyruvate. Genomic analysis
      identified a gene coding for a putative coenzyme A transferase. The gene was
      heterologously expressed in Escherichia coli and shown to code for succinyl-CoA:d
      citramalate coenzyme A transferase. This enzyme, which catalyzes the reaction d
      citramalate + succinyl-CoA --> d-citramalyl-CoA + succinate, was purified and
      studied. It belongs to class III of the coenzyme A transferase enzyme family,
      with an aspartate residue in the active site. The homodimeric enzyme composed of
      44-kDa subunits was specific for succinyl-CoA as a CoA donor but also accepted d
      malate and itaconate instead of d-citramalate. The CoA transferase gene is part
      of a cluster of genes which are cotranscribed, including the gene for d
      citramalyl-CoA lyase. It is proposed that the CoA transferase and the lyase
      catalyze the last two steps in the glyoxylate assimilation route.

PMID- 16952936
TI  - Gliding motility of Mycoplasma mobile can occur by repeated binding to N
      acetylneuraminyllactose (sialyllactose) fixed on solid surfaces.
AB  - Mycoplasma mobile relies on an unknown mechanism to glide across solid surfaces
      including glass, animal cells, and plastics. To identify the direct binding
      target, we examined the factors that affect the binding of Mycoplasma pneumoniae
      to solid surfaces and concluded that N-acetylneuraminyllactose (sialyllactose)
      attached to a protein can mediate glass binding on the basis of the following
      four lines of evidence: (i) glass binding was inhibited by N-acetylneuraminidase,
      (ii) glass binding was inhibited by N-acetylneuraminyllactose in a structure
      dependent manner, (iii) binding occurred on glass pretreated with bovine serum
      albumin attached to N-acetylneuraminyllactose, and (iv) gliding speed depended on
      the density of N-acetylneuraminyllactose on glass.

PMID- 16952937
TI  - The hmuQ and hmuD genes from Bradyrhizobium japonicum encode heme-degrading
      enzymes.
AB  - Utilization of heme by bacteria as a nutritional iron source involves the
      transport of exogenous heme, followed by cleavage of the heme macrocycle to
      release iron. Bradyrhizobium japonicum can use heme as an iron source, but no
      heme-degrading oxygenase has been described. Here, bioinformatics analyses of the
      B. japonicum genome identified two paralogous genes renamed hmuQ (bll7075) and
      hmuD (bll7423) that encode proteins with weak similarity to the heme-degrading
      monooxygenase IsdG from Staphylococcus aureus. The hmuQ gene is clustered with
      known heme transport genes in the genome. Recombinant HmuQ bound heme with a K(d)
      value of 0.8 microM and showed spectral properties consistent with a heme
      oxygenase. In the presence of a reductant, HmuQ catalyzed the degradation of heme
      and the formation of biliverdin. The hmuQ and hmuD genes complemented a
      Corynebacterium ulcerans heme oxygenase mutant in trans for utilization of heme
      as the sole iron source for growth. Furthermore, homologs of hmuQ and hmuD were
      identified in many bacterial genera, and the recombinant homolog from Brucella
      melitensis bound heme and catalyzed its degradation. The findings show that hmuQ
      and hmuD encode heme oxygenases and indicate that the IsdG family of heme
      degrading monooxygenases is not restricted to gram-positive pathogenic bacteria.

PMID- 16952938
TI  - The AlgT-dependent transcriptional regulator AmrZ (AlgZ) inhibits flagellum
      biosynthesis in mucoid, nonmotile Pseudomonas aeruginosa cystic fibrosis
      isolates.
AB  - Pseudomonas aeruginosa is a microorganism associated with the disease cystic
      fibrosis. While environmental P. aeruginosa strains are generally nonmucoid and
      motile, isolates recovered from the cystic fibrosis lung frequently display a
      mucoid, nonmotile phenotype. This phenotypic conversion is mediated by the
      alternative sigma factor AlgT. Previous work has shown that repression of fleQ by
      AlgT accounts for the loss of flagellum biosynthesis in these strains. Here, we
      elucidate the mechanism involved in the AlgT-mediated control of fleQ.
      Electrophoretic mobility shift assays using purified AlgT and extracts derived
      from isogenic AlgT(+) and AlgT(-) strains revealed that AlgT inhibits fleQ
      indirectly. We observed that the AlgT-dependent transcriptional regulator AmrZ
      interacts directly with the fleQ promoter. To determine whether AmrZ functions as
      a repressor of fleQ, we mutated amrZ in the mucoid, nonmotile P. aeruginosa
      strain FRD1. Unlike the parental strain, the amrZ mutant was nonmucoid and
      motile. Complementation of the mutant with amrZ restored the mucoid, nonmotile
      phenotype. Thus, our data show that AlgT inhibits flagellum biosynthesis in
      mucoid, nonmotile P. aeruginosa cystic fibrosis isolates by promoting expression
      of AmrZ, which subsequently represses fleQ. Since fleQ directly or indirectly
      controls the expression of almost all flagellar genes, its repression ultimately
      leads to the loss of flagellum biosynthesis.

PMID- 16952939
TI  - AphB influences acid tolerance of Vibrio vulnificus by activating expression of
      the positive regulator CadC.
AB  - A mutant of Vibrio vulnificus that was more sensitive to low pH was screened from
      a library of mutants constructed by random transposon mutagenesis. By use of a
      transposon-tagging method, an open reading frame encoding a LysR homologue, AphB,
      was identified and cloned from V. vulnificus. The deduced amino acid sequence of
      AphB from V. vulnificus was 80% identical to that reported from V. cholerae. A
      mutational analysis demonstrated that the gene product of aphB contributes to
      acid tolerance of V. vulnificus. The lysine decarboxylase activity and cellular
      level of the cadA transcript were decreased in the aphB mutant, indicating that
      AphB exerts its effect on the acid tolerance of V. vulnificus by enhancing the
      expression of cadBA. Western blot analyses demonstrated that the cellular level
      of CadC, a transcription activator of the cadBA operon, was significantly reduced
      by aphB mutation, and a primer extension analysis revealed that the cadC promoter
      (P(cadC)) activity was under the positive control of AphB. A direct interaction
      between AphB and the P(cadC) DNA was demonstrated by gel mobility shift assays.
      The AphB binding site mapped by deletion analyses of the P(cadC) regulatory
      region and confirmed by a DNase I protection assay was centered at the 61.5 bp
      upstream of the transcription start site. Accordingly, these results demonstrate
      that AphB and CadC function sequentially in a regulatory cascade to activate
      cadBA expression and that AphB activates the expression of cadC by directly
      binding to an upstream region of P(cadC).

PMID- 16952940
TI  - Tungsten transport protein A (WtpA) in Pyrococcus furiosus: the first member of a
      new class of tungstate and molybdate transporters.
AB  - A novel tungstate and molybdate binding protein has been discovered from the
      hyperthermophilic archaeon Pyrococcus furiosus. This tungstate transport protein
      A (WtpA) is part of a new ABC transporter system selective for tungstate and
      molybdate. WtpA has very low sequence similarity with the earlier-characterized
      transport proteins ModA for molybdate and TupA for tungstate. Its structural gene
      is present in the genome of numerous archaea and some bacteria. The
      identification of this new tungstate and molybdate binding protein clarifies the
      mechanism of tungstate and molybdate transport in organisms that lack the known
      uptake systems associated with the ModA and TupA proteins, like many archaea. The
      periplasmic protein of this ABC transporter, WtpA (PF0080), was cloned and
      expressed in Escherichia coli. Using isothermal titration calorimetry, WtpA was
      observed to bind tungstate (dissociation constant [K(D)] of 17 +/- 7 pM) and
      molybdate (K(D) of 11 +/- 5 nM) with a stoichiometry of 1.0 mol oxoanion per mole
      of protein. These low K(D) values indicate that WtpA has a higher affinity for
      tungstate than do ModA and TupA and an affinity for molybdate similar to that of
      ModA. A displacement titration of molybdate-saturated WtpA with tungstate showed
      that the tungstate effectively replaced the molybdate in the binding site of the
      protein.

PMID- 16952941
TI  - Functional characterization of IS1999, an IS4 family element involved in
      mobilization and expression of beta-lactam resistance genes.
AB  - IS1999 and a point mutant derivative, IS1999.2, have been described inserted
      upstream of emerging antibiotic resistance genes bla(VEB-1) and bla(OXA-48). 5'
      Rapid amplification of cDNA ends experiments revealed that expression of these
      beta-lactamase genes was driven by the outward-directed promoter, P(out), located
      in the IS1999 elements. These findings led us to study IS1999-mediated gene
      mobilization. Thus, the transposition properties of IS1999 and of IS1999-based
      composite transposons, made of two copies of IS1999 in different orientations,
      were investigated. IS1999 or IS1999-based composite transposons were capable of
      transposing onto the conjugative plasmid pOX38-Gen. Sequence analysis of the
      insertion sites revealed that IS1999 inserted preferentially into DNA targets
      containing the consensus sequence NGCNNNGCN. Transposition was more efficient
      when at least one left inverted repeat end was located at an outside end of the
      transposon. The transposition frequency of IS1999.2 was 10-fold lower than that
      of IS1999, and transposition frequencies of the putative natural transposon,
      Tn1999, were below detection limits of our transposition assay. This reduced
      transposition frequency of IS1999.2-based elements may result from a lower
      transcription of the transposase gene, as revealed by reverse transcription-PCR
      analyses.

PMID- 16952942
TI  - Characterization of ferric and ferrous iron transport systems in Vibrio cholerae.
AB  - Vibrio cholerae has multiple iron acquisition systems, including TonB-dependent
      transport of heme and of the catechol siderophore vibriobactin. Strains defective
      in both of these systems grow well in laboratory media and in the infant mouse
      intestine, indicating the presence of additional iron acquisition systems.
      Previously uncharacterized potential iron transport systems, including a
      homologue of the ferrous transporter Feo and a periplasmic binding protein
      dependent ATP binding cassette (ABC) transport system, termed Fbp, were
      identified in the V. cholerae genome sequence. Clones encoding either the Feo or
      the Fbp system exhibited characteristics of iron transporters: both repressed the
      expression of lacZ cloned under the control of a Fur-regulated promoter in
      Escherichia coli and also conferred growth on a Shigella flexneri mutant that has
      a severe defect in iron transport. Two other ABC transporters were also evaluated
      but were negative by these assays. Transport of radioactive iron by the Feo
      system into the S. flexneri iron transport mutant was stimulated by the reducing
      agent ascorbate, consistent with Feo functioning as a ferrous transporter.
      Conversely, ascorbate inhibited transport by the Fbp system, suggesting that it
      transports ferric iron. The growth of V. cholerae strains carrying mutations in
      one or more of the potential iron transport genes indicated that both Feo and Fbp
      contribute to iron acquisition. However, a mutant defective in the vibriobactin,
      Fbp, and Feo systems was not attenuated in a suckling mouse model, suggesting
      that at least one other iron transport system can be used in vivo.

PMID- 16952943
TI  - 3-Hydroxy-3-methylglutaryl-coenzyme A (CoA) synthase is involved in biosynthesis
      of isovaleryl-CoA in the myxobacterium Myxococcus xanthus during fruiting body
      formation.
AB  - Isovaleryl-coenzyme A (IV-CoA) is the starting unit for some secondary
      metabolites and iso-odd fatty acids in several bacteria. According to textbook
      biochemistry, IV-CoA is derived from leucine degradation, but recently an
      alternative pathway that branches from the well-known mevalonate-dependent
      isoprenoid biosynthesis has been described for myxobacteria. A double mutant was
      constructed in Myxococcus xanthus by deletion of genes involved in leucine
      degradation and disruption of mvaS encoding the 3-hydroxy-3-methylglutaryl
      coenzyme A synthase. A dramatic decrease of IV-CoA-derived iso-odd fatty acids
      was observed for the mutant, confirming mvaS to be involved in the alternative
      pathway. Additional quantitative real-time reverse transcription-PCR experiments
      indicated that mvaS is transcriptionally regulated by isovalerate. Furthermore,
      feeding studies employing an intermediate specific for the alternative pathway
      revealed that this pathway is induced during fruiting body formation, which
      presumably increases the amount of IV-CoA available when leucine is limited.

PMID- 16952944
TI  - The Pseudomonas aeruginosa universal stress protein PA4352 is essential for
      surviving anaerobic energy stress.
AB  - During infection of the cystic fibrosis (CF) lung, Pseudomonas aeruginosa
      microcolonies are embedded in the anaerobic CF mucus. This anaerobic environment
      seems to contribute to the formation of more robust P. aeruginosa biofilms and to
      an increased antibiotic tolerance and therefore promotes persistent infection.
      This study characterizes the P. aeruginosa protein PA4352, which is important for
      survival under anaerobic energy stress conditions. PA4352 belongs to the
      universal stress protein (Usp) superfamily and harbors two Usp domains in tandem.
      In Escherichia coli, Usp-type stress proteins are involved in survival during
      aerobic growth arrest and under various other stresses. A P. aeruginosa PA4352
      knockout mutant was tested for survival under several stress conditions. We found
      a decrease in viability of this mutant compared to the P. aeruginosa wild type
      during anaerobic energy starvation caused by the missing electron acceptors
      oxygen and nitrate. Consistent with this phenotype under anaerobic conditions,
      the PA4352 knockout mutant was also highly sensitive to carbonyl cyanide m
      chlorophenylhydrazone, the chemical uncoupler of the electron transport chain.
      Primer extension experiments identified two promoters upstream of the PA4352
      gene. One promoter is activated in response to oxygen limitation by the oxygen
      sensing regulatory protein Anr. The center of a putative Anr binding site was
      identified 41.5 bp upstream of the transcriptional start site. The second
      promoter is active only in the stationary phase, however, independently of RpoS,
      RelA, or quorum sensing. This is the second P. aeruginosa Usp-type stress protein
      that we have identified as important for survival under anaerobic conditions,
      which resembles the environment during persistent infection.

PMID- 16952945
TI  - Hundreds of flagellar basal bodies cover the cell surface of the endosymbiotic
      bacterium Buchnera aphidicola sp. strain APS.
AB  - Buchnera aphidicola is the endosymbiotic bacterium of the pea aphid. Due to its
      small genome size, Buchnera lacks many essential genes for autogenous life but
      obtains nutrients from the host. Although the Buchnera cell is nonmotile, it
      retains clusters of flagellar genes that lack the late genes necessary for
      motility, including the flagellin gene. In this study, we show that the flagellar
      genes are actually transcribed and translated and that the Buchnera cell surface
      is covered with hundreds of hook-basal-body (HBB) complexes. The abundance of HBB
      complexes suggests a role other than motility. We discuss the possibility that
      the HBB complex may serve as a protein transporter not only for the flagellar
      proteins but also for other proteins to maintain the symbiotic system.

PMID- 16952946
TI  - Both subunits of ATP-citrate lyase from Chlorobium tepidum contribute to
      catalytic activity.
AB  - ATP-citrate lyase (ACL) is an essential enzyme of the reductive tricarboxylic
      acid (RTCA) pathway of CO(2) assimilation. The RTCA pathway occurs in several
      groups of autotrophic prokaryotes, including the green sulfur bacteria. ACL
      catalyzes the coenzyme A (CoA)-dependent and MgATP-dependent cleavage of citrate
      into oxaloacetate and acetyl-CoA, representing a key step in the RTCA pathway. To
      characterize this enzyme from the green sulfur bacterium Chlorobium tepidum and
      determine the role of its two distinct polypeptide chains, recombinant holo-ACL
      as well as its two individual subunit polypeptides were synthesized in
      Escherichia coli. The recombinant holoenzyme, prepared from coexpressed large and
      small ACL genes, and the individual large and small subunit polypeptides,
      prepared from singly expressed genes, were all purified to homogeneity to high
      yield. Purified recombinant holo-ACL was isolated at high specific activity, and
      its k(cat) was comparable to that of previously prepared native C. tepidum ACL.
      Moreover, the purified recombinant large and small subunit polypeptides were able
      to reconstitute the holo-ACL in vitro, with activity levels approaching that of
      recombinant holo-ACL prepared from coexpressed genes. Stoichiometric amounts of
      each subunit protein were required to maximize the activity and form the most
      stable structure of reconstituted holo-ACL. These results suggested that this
      reconstitution system could be used to discern the catalytic role of specific
      amino acid residues on each subunit. Reconstitution and mutagenesis studies
      together indicated that residues of each subunit contributed to different aspects
      of the catalytic mechanism, suggesting that both subunit proteins contribute to
      the active site of C. tepidum ACL.

PMID- 16952947
TI  - Hypoxanthine incorporation is nonmutagenic in Escherichia coli.
AB  - Endonuclease V, encoded by the nfi gene, initiates removal of the base analogs
      hypoxanthine and xanthine from DNA, acting to prevent mutagenesis from purine
      base deamination within the DNA. On the other hand, the RdgB nucleotide hydrolase
      in Escherichia coli is proposed to prevent hypoxanthine and xanthine
      incorporation into DNA by intercepting the noncanonical DNA precursors dITP and
      dXTP. Because many base analogs are mutagenic when incorporated into DNA, it is
      intuitive to think of RdgB as acting to prevent similar mutagenesis from
      deaminated purines in the DNA precursor pools. To test this idea, we used a set
      of Claire Cupples' strains to detect changes in spontaneous mutagenesis spectra,
      as well as in nitrous acid-induced mutagenesis spectra, in wild-type cells and in
      rdgB single, nfi single, and rdgB nfi double mutants. We found neither a
      significant increase in spontaneous mutagenesis in rdgB and nfi single mutants or
      the double mutant nor any changes in nitrous acid-induced mutagenesis for rdgB
      mutant strains. We conclude that incorporation of deaminated purines into DNA is
      nonmutagenic.

PMID- 16952948
TI  - Mlc of Thermus thermophilus: a glucose-specific regulator for a glucose/mannose
      ABC transporter in the absence of the phosphotransferase system.
AB  - We report the presence of Mlc in a thermophilic bacterium. Mlc is known as a
      global regulator of sugar metabolism in gram-negative enteric bacteria that is
      controlled by sequestration to a glucose-transporting EII(Glc) of the
      phosphotransferase system (PTS). Since thermophilic bacteria do not possess PTS,
      Mlc in Thermus thermophilus must be differently controlled. DNA sequence
      alignments between Mlc from T. thermophilus (Mlc(Tth)) and Mlc from E. coli
      (Mlc(Eco)) revealed that Mlc(Tth) conserved five residues of the glucose-binding
      motif of glucokinases. Here we show that Mlc(Tth) is not a glucokinase but is
      indeed able to bind glucose (K(D) = 20 microM), unlike Mlc(Eco). We found that
      mlc of T. thermophilus is the first gene within an operon encoding an ABC
      transporter for glucose and mannose, including a glucose/mannose-binding protein
      and two permeases. malK1, encoding the cognate ATP-hydrolyzing subunit, is
      located elsewhere on the chromosome. The system transports glucose at 70 degrees
      C with a K(m) of 0.15 microM and a V(max) of 4.22 nmol per min per ml at an
      optical density (OD) of 1. Mlc(Tth) negatively regulates itself and the entire
      glucose/mannose ABC transport system operon but not malK1, with glucose acting as
      an inducer. MalK1 is shared with the ABC transporter for trehalose, maltose,
      sucrose, and palatinose (TMSP). Mutants lacking malK1 do not transport either
      glucose or maltose. The TMSP transporter is also able to transport glucose with a
      K(m) of 1.4 microM and a V(max) of 7.6 nmol per min per ml at an OD of 1, but it
      does not transport mannose.

PMID- 16952949
TI  - Characteristic features in the structure and collagen-binding ability of a
      thermophilic collagenolytic protease from the thermophile Geobacillus
      collagenovorans MO-1.
AB  - A collagen-degrading thermophile, Geobacillus collagenovorans MO-1,
      extracellularly produces a collagenolytic protease with a large molecular mass.
      Complete nucleotide sequencing of this gene after gene cloning revealed that the
      collagenolytic protease is a member of the subtilisin family of serine proteases
      and consists of a signal sequence for secretion, a prosequence for maturation, a
      catalytic region, 14 direct repeats of 20 amino acids at the C terminus, and a
      region with unknown function intervening between the catalytic region and the
      numerous repeats. Since the unusual repeats are most likely to be cleaved in the
      secreted form of the enzyme, the intervening region was investigated to determine
      whether it participates in collagen binding to facilitate collagen degradation.
      It was found that the mature collagenolytic protease containing the intervening
      region at the C terminus bound collagen but not the other insoluble proteins,
      elastin and keratin. Furthermore, the intervening region fused with glutathione S
      transferase showed a collagen-binding ability comparable to that of the mature
      collagenolytic protease. The collagen-binding ability was finally attributed to
      two-thirds of the intervening region which is rich in beta-strands and is
      approximately 35 kDa in molecular mass. In the collagenolytic protease from
      strain MO-1, hydrogen bonds most likely predominate over the hydrophobic
      interaction for collagen binding, since a higher concentration of NaCl released
      collagen from the enzyme surface but a nonionic detergent could not. To the best
      of our knowledge, this is the first report of a thermophilic collagenolytic
      protease containing the collagen-binding segment.

PMID- 16952951
TI  - Identification of a novel galactosyl transferase involved in biosynthesis of the
      mycobacterial cell wall.
AB  - The possibility of the Rv3782 protein of Mycobacterium tuberculosis being a
      putative galactosyl transferase (GalTr) implicated in galactan synthesis arose
      from its similarity to the known GalTr Rv3808c, its classification as a
      nucleotide sugar-requiring inverting glycosyltransferase (GT-2 family), and its
      location within the "possible arabinogalactan biosynthetic gene cluster" of M.
      tuberculosis. In order to study the function of the enzyme, active membrane and
      cell wall fractions from Mycobacterium smegmatis containing the overexpressed
      Rv3782 protein were incubated with endogenous decaprenyldiphosphoryl-N
      acetylglucosaminyl-rhamnose (C(50)-P-P-GlcNAc-Rha) as the primary substrate for
      galactan synthesis and UDP-[(14)C]galactopyranose as the immediate precursor of
      UDP-[(14)C]galactofuranose, the ultimate source of all of the galactofuranose
      (Galf) units of galactan. Obvious increased and selective synthesis of C(50)-P-P
      GlcNAc-Rha-Galf-Galf, the earliest product in the pathway leading to the fully
      polymerized galactan, was observed, suggesting that Rv3782 encodes a GalTr
      involved in the first stages of galactan synthesis. Time course experiments
      pointed to a possible bifunctional enzyme responsible for the initial synthesis
      of C(50)-P-P-GlcNAc-Rha-Galf, followed by immediate conversion to C(50)-P-P
      GlcNAc-Rha-Galf-Galf. Thus, Rv3782 appears to be the initiator of galactan
      synthesis, while Rv3808c continues with the subsequent polymerization events.

PMID- 16952950
TI  - Identification of an essential gene of Listeria monocytogenes involved in
      teichoic acid biogenesis.
AB  - Listeria monocytogenes is a facultative intracellular gram-positive bacterium
      responsible for severe opportunistic infections in humans and animals. We had
      previously identified a gene encoding a putative UDP-N-acetylglucosamine 2
      epimerase, a precursor of the teichoic acid linkage unit, in the genome of L
      monocytogenes strain EGD-e. This gene, now designated lmo2537, encodes a protein
      that shares 62% identity with the cognate epimerase MnaA of Bacillus subtilis and
      55% identity with Cap5P of Staphylococcus aureus. Here, we addressed the role of
      lmo2537 in L. monocytogenes pathogenesis by constructing a conditional knockout
      mutant. The data presented here demonstrate that lmo2537 is an essential gene of
      L. monocytogenes that is involved in teichoic acid biogenesis. In vivo, the
      conditional mutant is very rapidly eliminated from the target organs of infected
      mice and thus is totally avirulent.

PMID- 16952952
TI  - Intraspecific variability of the terminal inverted repeats of the linear
      chromosome of Streptomyces ambofaciens.
AB  - The sequences of the terminal inverted repeats (TIRs) ending the linear
      chromosomal DNA of two Streptomyces ambofaciens strains, ATCC23877 and DSM40697
      (198 kb and 213 kb, respectively), were determined from two sets of recombinant
      cosmids. Among the 215 coding DNA sequences (CDSs) predicted in the TIRs of
      strain DSM40697, 65 are absent in the TIRs of strain ATCC23877. Reciprocally, 45
      of the 194 predicted CDSs are specific to the ATCC23877 strain. The strain
      specific CDSs are located mainly at the terminal end of the TIRs. Indeed,
      although TIRs appear almost identical over 150 kb (99% nucleotide identity),
      large regions of DNA of 60 kb (DSM40697) and 48 kb (ATCC23877), mostly spanning
      the ends of the chromosome, are strain specific. These regions are rich in
      plasmid-associated genes, including genes encoding putative conjugal transfer
      functions. The strain-specific regions also share a G+C content (68%) lower than
      that of the rest of the genome (from 71% to 73%), a percentage that is more
      typical of Streptomyces plasmids and mobile elements. These data suggest that
      exchanges of replicon extremities have occurred, thereby contributing to the
      terminal variability observed at the intraspecific level. In addition, the
      terminal regions include many mobile genetic element-related genes, pseudogenes,
      and genes related to adaptation. The results give insight into the mechanisms of
      evolution of the TIRs: integration of new information and/or loss of DNA
      fragments and subsequent homogenization of the two chromosomal extremities.

PMID- 16952953
TI  - Expression and assembly of a functional type IV secretion system elicit
      extracytoplasmic and cytoplasmic stress responses in Escherichia coli.
AB  - Conditions perturbing protein homeostasis are known to induce cellular stress
      responses in prokaryotes and eukaryotes. Here we show for the first time that
      expression and assembly of a functional type IV secretion (T4S) machinery elicit
      extracytoplasmic and cytoplasmic stress responses in Escherichia coli. After
      induction of T4S genes by a nutritional upshift and assembly of functional DNA
      transporters encoded by plasmid R1-16, host cells activated the CpxAR envelope
      stress signaling system, as revealed by induction or repression of downstream
      targets of the CpxR response regulator. Furthermore, we observed elevated
      transcript levels of cytoplasmic stress genes, such as groESL, with a concomitant
      increase of sigma(32) protein levels in cells expressing T4S genes. A traA null
      mutant of plasmid R1-16, which lacks the functional gene encoding the major pilus
      protein pilin, showed distinctly reduced stress responses. These results
      corroborated our conclusion that the activation of bacterial stress networks was
      dependent on the presence of functional T4S machinery. Additionally, we detected
      increased transcription from the rpoHp(1) promoter in the presence of an active
      T4S system. Stimulation of rpoHp(1) was dependent on the presence of CpxR,
      suggesting a hitherto undocumented link between CpxAR and sigma(32)-regulated
      stress networks.

PMID- 16952954
TI  - DsdX is the second D-serine transporter in uropathogenic Escherichia coli
      clinical isolate CFT073.
AB  - d-Serine is an amino acid present in mammalian urine that is inhibitory to
      Escherichia coli strains lacking a functional dsdA gene. Counterintuitively, a
      dsdA strain of E. coli clinical isolate CFT073 hypercolonizes the bladder and
      kidneys of mice relative to wild type during a coinfection in the murine model of
      urinary tract infection. We are interested in the mechanisms for uptake of d
      serine in CFT073. d-Serine enters E. coli K-12 via CycA, the d-alanine
      transporter and d-cycloserine sensitivity locus. CFT073 cycA can grow on minimal
      medium with d-serine as a sole carbon source. The dsdX gene of the dsdCXA locus
      is a likely candidate for an additional d-serine transporter based on its
      predicted amino acid sequence similarity to gluconate transporters. In minimal
      medium, CFT073 dsdX can grow on d-serine as a sole carbon source; however, CFT073
      dsdX cycA cannot. Additionally, CFT073 dsdXA cycA is not sensitive to inhibitory
      concentrations of d-serine during growth on glycerol and d-serine minimal medium.
      d-[(14)C]serine uptake experiments with CFT073 dsdX cycA harboring dsdX or cycA
      recombinant plasmids confirm that d-serine is able to enter E. coli cells via
      CycA or DsdX. In whole-cell d-[(14)C]serine uptake experiments, DsdX has an
      apparent K(m) of 58.75 microM and a V(max) of 75.96 nmol/min/mg, and CycA has an
      apparent K(m) of 82.40 microM and a V(max) of 58.90 nmol/min/mg. Only d-threonine
      marginally inhibits DsdX-mediated d-serine transport, whereas d-alanine, glycine,
      and d-cycloserine inhibit CycA-mediated d-serine transport. DsdX or CycA is
      sufficient to transport physiological quantities of d-serine, but DsdX is a d
      serine-specific permease.

PMID- 16952955
TI  - Sequence analysis of the lactococcal plasmid pNP40: a mobile replicon for coping
      with environmental hazards.
AB  - The conjugative lactococcal plasmid pNP40, identified in Lactococcus lactis
      subsp. diacetylactis DRC3, possesses a potent complement of bacteriophage
      resistance systems, which has stimulated its application as a fitness-improving,
      food-grade genetic element for industrial starter cultures. The complete sequence
      of this plasmid allowed the mapping of previously known functions including
      replication, conjugation, bacteriocin resistance, heavy metal tolerance, and
      bacteriophage resistance. In addition, functions for cold shock adaptation and
      DNA damage repair were identified, further confirming pNP40's contribution to
      environmental stress protection. A plasmid cointegration event appears to have
      been part of the evolution of pNP40, resulting in a "stockpiling" of
      bacteriophage resistance systems.

PMID- 16952957
TI  - Granular layer in the periplasmic space of gram-positive bacteria and fine
      structures of Enterococcus gallinarum and Streptococcus gordonii septa revealed
      by cryo-electron microscopy of vitreous sections.
AB  - High-resolution structural information on optimally preserved bacterial cells can
      be obtained with cryo-electron microscopy of vitreous sections. With the help of
      this technique, the existence of a periplasmic space between the plasma membrane
      and the thick peptidoglycan layer of the gram-positive bacteria Bacillus subtilis
      and Staphylococcus aureus was recently shown. This raises questions about the
      mode of polymerization of peptidoglycan. In the present study, we report the
      structure of the cell envelope of three gram-positive bacteria (B. subtilis,
      Streptococcus gordonii, and Enterococcus gallinarum). In the three cases, a
      previously undescribed granular layer adjacent to the plasma membrane is found in
      the periplasmic space. In order to better understand how nascent peptidoglycan is
      incorporated into the mature peptidoglycan, we investigated cellular regions
      known to represent the sites of cell wall production. Each of these sites
      possesses a specific structure. We propose a hypothetic model of peptidoglycan
      polymerization that accommodates these differences: peptidoglycan precursors
      could be exported from the cytoplasm to the periplasmic space, where they could
      diffuse until they would interact with the interface between the granular layer
      and the thick peptidoglycan layer. They could then polymerize with mature
      peptidoglycan. We report cytoplasmic structures at the E. gallinarum septum that
      could be interpreted as cytoskeletal elements driving cell division (FtsZ ring).
      Although immunoelectron microscopy and fluorescence microscopy studies have
      demonstrated the septal and cytoplasmic localization of FtsZ, direct
      visualization of in situ FtsZ filaments has not been obtained in any electron
      microscopy study of fixed and dehydrated bacteria.

PMID- 16952956
TI  - Control of enterotoxin gene expression in Bacillus cereus F4430/73 involves the
      redox-sensitive ResDE signal transduction system.
AB  - In contrast to Bacillus subtilis, the role of the two-component regulatory system
      ResDE has not yet been investigated in the facultative anaerobe Bacillus cereus.
      We examined the role of ResDE in the food-borne pathogen B. cereus F4430/73 by
      constructing resDE and resE mutants. Growth performances, glucose metabolism, and
      expression of hemolysin BL (Hbl) and nonhemolytic enterotoxin (Nhe) were analyzed
      in the three strains under distinct oxygenation and extracellular oxidoreduction
      potential (ORP) conditions. We show that growth and glucose metabolism were only
      moderately perturbed in both resDE and resE mutants under aerobiosis,
      microaerobiosis, and anaerobiosis generated under N(2) atmosphere (initial ORP =
      +45 mV). The major effects of resDE and resE mutations were observed under low
      ORP anaerobic conditions generated under hydrogen atmosphere (iORP = -148 mV).
      These conditions normally favor enterotoxin production in the wild type. The resE
      mutation was more deleterious to the cells than the resDE mutation, causing
      growth limitation and strong deregulation of key catabolic genes. More
      importantly, the resE mutation abolished the production of enterotoxins under all
      of the conditions examined. The resDE mutation only decreased enterotoxin
      expression under anaerobiosis, with a more pronounced effect under low-ORP
      conditions. Thus, the ResDE system was found to exert major control on both
      fermentative growth and enterotoxin expression, and it is concluded that the
      ResDE system of B. cereus should be considered an anaerobic redox regulator. The
      data presented also provide evidence that the ResDE-dependent regulation of
      enterotoxins might function at least partially independently of the pleiotropic
      virulence gene regulator PlcR.

PMID- 16952958
TI  - Thiamine is synthesized by a salvage pathway in Rhizobium leguminosarum bv.
      viciae strain 3841.
AB  - In the absence of added thiamine, Rhizobium leguminosarum bv. viciae strain 3841
      does not grow in liquid medium and forms only "pin" colonies on agar plates,
      which contrasts with the good growth of Sinorhizobium meliloti 1021,
      Mesorhizobium loti 303099, and Rhizobium etli CFN42. These last three organisms
      have thiCOGE genes, which are essential for de novo thiamine synthesis. While R.
      leguminosarum bv. viciae 3841 lacks thiCOGE, it does have thiMED. Mutation of
      thiM prevented formation of pin colonies on agar plates lacking added thiamine,
      suggesting thiamine intermediates are normally present. The putative functions of
      ThiM, ThiE, and ThiD are 4-methyl-5-(beta-hydroxyethyl) thiazole (THZ) kinase,
      thiamine phosphate pyrophosphorylase, and 4-amino-5-hydroxymethyl-2-methyl
      pyrimidine (HMP) kinase, respectively. This suggests that a salvage pathway
      operates in R. leguminosarum, and addition of HMP and THZ enabled growth at the
      same rate as that enabled by thiamine in strain 3841 but elicited no growth in
      the thiM mutant (RU2459). There is a putative thi box sequence immediately
      upstream of the thiM, and a gfp-mut3.1 fusion to it revealed the presence of a
      promoter that is strongly repressed by thiamine. Using fluorescent microscopy and
      quantitative reverse transcription-PCR, it was shown that thiM is expressed in
      the rhizosphere of vetch and pea plants, indicating limitation for thiamine. Pea
      plants infected by RU2459 were not impaired in nodulation or nitrogen fixation.
      However, colonization of the pea rhizosphere by the thiM mutant was impaired
      relative to that of the wild type. Overall, the results show that a thiamine
      salvage pathway operates to enable growth of Rhizobium leguminosarum in the
      rhizosphere, allowing its survival when thiamine is limiting.

PMID- 16952959
TI  - Inactivation of Rv2525c, a substrate of the twin arginine translocation (Tat)
      system of Mycobacterium tuberculosis, increases beta-lactam susceptibility and
      virulence.
AB  - The twin arginine translocation (Tat) system is used by many bacteria to export
      fully folded proteins containing cofactors. Here, we show genetically that this
      system is essential for Mycobacterium tuberculosis, as the tatAC operon and tatB
      genes could be inactivated only in partially diploid strains. Using comparative
      genomics, the rv2525c gene of M. tuberculosis was identified as encoding a
      histidine-rich protein, with a twin arginine signal peptide, and orthologous
      genes were shown to be present in several but not all actinobacterial species.
      Conservation of this gene by Mycobacterium leprae, which has undergone reductive
      evolution, suggested an important role for rv2525c. An rv2525c knockout mutant
      was constructed, and biochemical analysis indicated that the mature Rv2525c
      protein is secreted. Upon exposure to antituberculous drugs, rv2525c expression
      is significantly up-regulated together with those of other genes involved in cell
      wall biogenesis. Phenotypic comparison of the mutant with the parental strain
      revealed an increase in susceptibility to some beta-lactam antibiotics and,
      despite slower growth in vitro, enhanced virulence in both cellular and murine
      models of tuberculosis. The Tat system thus contributes in multiple ways to
      survival of the tubercle bacillus.

PMID- 16952960
TI  - Expression of the primary carbohydrate component of the Bordetella bronchiseptica
      biofilm matrix is dependent on growth phase but independent of Bvg regulation.
AB  - We previously showed that the Bvg virulence control system regulates biofilm
      formation in Bordetella bronchiseptica (Y. Irie, S. Mattoo, and M. H. Yuk, J.
      Bacteriol. 186:5692-5698, 2004). Analyses of the extracellular components of B.
      bronchiseptica biofilm matrix revealed that the major sugar component in the
      matrix was xylose, and linkage analysis indicated a majority of it to be in a 4
      linked polymeric form. The production of xylose was independent of Bvg regulation
      but instead was dependent on bacterial growth phase. In addition, N-acetyl
      glucosamine in the matrix was found to be important for the initial development
      of the biofilm. These results suggest that B. bronchiseptica biofilm formation is
      growth phase dependent in addition to being regulated by the Bvg virulence
      system.

PMID- 16952961
TI  - Signal transduction genes required for heterocyst maturation in Anabaena sp.
      strain PCC 7120.
AB  - How heterocyst differentiation is regulated, once particular cells start to
      differentiate, remains largely unknown. Using near-saturation transposon
      mutagenesis and testing of transposon-tagged loci, we identified three
      presumptive regulatory genes not previously recognized as being required
      specifically for normal heterocyst maturation. One of these genes has a hitherto
      unreported mutant phenotype. Two previously identified regulatory genes were
      further characterized.

PMID- 16952962
TI  - Localized induction of the ntcA regulatory gene in developing heterocysts of
      Anabaena sp. strain PCC 7120.
AB  - The ntcA gene encodes an N-control transcriptional regulator in cyanobacteria. In
      the N(2)-fixing, heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120,
      ntcA is an autoregulatory gene that is transcribed from a complex promoter region
      that includes a constitutive promoter (P(2)) and promoters that are induced upon
      N step-down (P(1) and P(3)). Expression of ntcA was investigated with the use of
      an ntcA-gfp translational fusion, which was introduced both in the natural ntcA
      locus and in a heterologous genomic place. Induction of ntcA-gfp took place after
      N step-down in all the cells of the filament, but at especially high levels in
      developing heterocysts. Localized induction could be driven independently by P(3)
      and P(1).

PMID- 16952963
TI  - Identification and characterization of the chemotactic transducer in Pseudomonas
      aeruginosa PAO1 for positive chemotaxis to trichloroethylene.
AB  - Pseudomonas aeruginosa PAO1 is repelled by trichloroethylene (TCE), and the
      methyl-accepting chemotaxis proteins PctA, PctB, and PctC serve as the major
      chemoreceptors for negative chemotaxis to TCE. In this study, we found that the
      pctABC triple mutant of P. aeruginosa PAO1 was attracted by TCE. Chemotaxis
      assays of a set of mutants containing deletions in 26 potential mcp genes
      revealed that mcpA (PA0180) is the chemoreceptor for positive chemotaxis to TCE.
      McpA also detects tetrachloroethylene and dichloroethylene isomers as
      attractants.

PMID- 16952964
TI  - FliT acts as an anti-FlhD2C2 factor in the transcriptional control of the
      flagellar regulon in Salmonella enterica serovar typhimurium.
AB  - Flagellar operons are divided into three classes with respect to their
      transcriptional hierarchy in Salmonella enterica serovar Typhimurium. The class 1
      gene products FlhD and FlhC act together in an FlhD(2)C(2) heterotetramer, which
      binds upstream of the class 2 promoters to facilitate binding of RNA polymerase.
      Class 2 expression is known to be enhanced by a disruption mutation in a
      flagellar gene, fliT. In this study, we purified FliT protein in a His-tagged
      form and showed that the protein prevented binding of FlhD(2)C(2) to the class 2
      promoter and inhibited FlhD(2)C(2)-dependent transcription. Pull-down and far
      Western blotting analyses revealed that the FliT protein was capable of binding
      to FlhD(2)C(2) and FlhC and not to FlhD alone. We conclude that FliT acts as an
      anti-FlhD(2)C(2) factor, which binds to FlhD(2)C(2) through interaction with the
      FlhC subunit and inhibits its binding to the class 2 promoter.

PMID- 16952966
TI  - Prognosis of stable angina pectoris: why we need larger population studies with
      higher endpoint resolution.
AB  - The prognosis of angina was described as "unhappy" by the Framingham
      investigators and as little different from that of 1-year survivors of acute
      myocardial infarction. Yet recent clinical trials now report that angina has a
      good prognosis with adverse outcomes reduced to "normal levels". These disparate
      prognostic assessments may not be incompatible, applying as they do to population
      cohorts (Framingham) and selected participants in clinical trials. Comparisons
      between studies are further complicated by the absence of agreed case definitions
      for stable angina (contrast this with acute coronary syndromes). Our recent data
      show that for patients with recent onset symptoms attending chest pain clinics,
      angina remains a high-risk diagnosis and although many patients receive
      symptomatic benefit from revascularisation, prognosis is usually unaffected. This
      leaves little room for complacency and, with angina the commonest initial
      manifestation of coronary artery disease, there is the opportunity for early
      detection, risk stratification and treatment to modify outcomes. Meanwhile,
      larger population-based studies are needed to define the patient journey from
      earliest presentation through the various syndrome transitions to coronary or
      noncardiac death in order to increase understanding of the aetiological and
      prognostic differences between the different coronary disease phenotypes.

PMID- 16952965
TI  - Transcriptional response of Escherichia coli to TPEN.
AB  - DNA microarrays were used to probe the transcriptional response of Escherichia
      coli to N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN). Fifty-five
      transcripts were significantly up-regulated, including all of the genes that are
      regulated by Zur and many that are regulated by Fur. In the same TPEN-treated
      cells, 46 transcripts were significantly down-regulated.

PMID- 16952968
TI  - The new NICE guideline on atrial fibrillation management.

PMID- 16952967
TI  - Three-dimensional CT scanning: a new diagnostic modality in congenital heart
      disease.
AB  - New generation multislice CT technology has changed the approach to non-invasive
      assessment of congenital heart disease, in both paediatric and adult patients.
      This is mainly because of rapid advances in spatial and temporal resolution and
      in post-processing capability. At Hopital Necker-Enfants Malades, CT with
      multiplanar and three-dimensional reconstruction has become a routine examination
      in the evaluation of congenital heart disease planning surgery, complex
      interventional catheterisations and for follow-up. It has proved to be an
      invaluable diagnostic and decision-aiding methodology in these situations, as a
      complement to echocardiography and, increasingly, as a substitute for diagnostic
      angiography (which is usually associated with higher-dose radiation and longer
      sedation times, as well as occasional morbidity). This review illustrates the
      current status of 64-slice CT in congenital heart diseases, including assessment
      of the aorta, the coronary arteries, the pulmonary arteries, the systemic and
      pulmonary veins, and other intra- and extracardiac malformations.

PMID- 16952969
TI  - Patient care pathway, implementation and audit criteria for patients with atrial
      fibrillation.

PMID- 16952970
TI  - Acute management of atrial fibrillation with acute haemodynamic instability and
      in the postoperative setting.

PMID- 16952971
TI  - Antithrombotic treatment in atrial fibrillation.

PMID- 16952972
TI  - Rate control in the medical management of atrial fibrillation.

PMID- 16952973
TI  - Identification, diagnosis and assessment of atrial fibrillation.

PMID- 16952974
TI  - Levels of homocysteine are increased in metabolic syndrome patients but are not
      associated with an increased cardiovascular risk, in contrast to patients without
      the metabolic syndrome.
AB  - AIM: The metabolic syndrome is associated with increased cardiovascular risk.
      Elevated plasma homocysteine may cause or result from insulin resistance, and may
      indicate vascular risk or be actively involved in atherogenesis. The aim of the
      study was to investigate the relationship between homocysteine, the metabolic
      syndrome and the incidence of cardiovascular events in patients with manifest
      vascular disease. METHODS: A cohort of 2169 patients with manifest vascular
      disease was followed for a mean period of 2.8 years. Plasma homocysteine was
      measured at baseline. Metabolic syndrome was defined by NCEP criteria. RESULTS:
      Homocysteine levels were higher in metabolic syndrome patients compared to
      patients without the metabolic syndrome (14.9+/-0.2 v 14.1+/-0.2 micromol/l; p =
      0.002) and increased with the presence of its components (from 0 to 5) (12.7 to
      15.9 micromol/l; p<0.001). During follow-up, 52 strokes, 67 myocardial
      infarctions, 5 fatal ruptures of aortic aneurysms and 53 vascular deaths
      occurred. Patients without the metabolic syndrome and homocysteine levels in the
      highest tertile had increased risk for events (HR 1.9; 95% CI 1.0 to 3.5)
      compared to patients without the metabolic syndrome and homocysteine levels in
      the lowest tertile. The presence of the metabolic syndrome increased the risk (HR
      2.2; 95% CI 1.2 to 4.2), but elevated homocysteine levels further increased the
      risk only marginally (2.5; 95% CI 1.4 to 4.6). CONCLUSIONS: Metabolic syndrome
      patients have elevated homocysteine levels, but these higher levels are not
      associated with an increased risk for new cardiovascular events. In contrast,
      elevated homocysteine levels confer increased risk in patients without the
      metabolic syndrome.

PMID- 16952975
TI  - Prevalence and prognostic implications of electrocardiographic left ventricular
      hypertrophy in heart failure: evidence from the CHARM programme.
AB  - BACKGROUND: Electrocardiographic left ventricular hypertrophy (ECG LVH) is a
      powerful independent predictor of cardiovascular morbidity and mortality in
      hypertension. OBJECTIVE: To determine the contemporary prevalence and prognostic
      implications of ECG LVH in a broad spectrum of patients with heart failure with
      and without reduced left ventricular ejection fraction (LVEF). METHODS AND
      OUTCOME: The Candesartan in Heart failure: Assessment of Reduction in Mortality
      and morbidity (CHARM) programme randomised 7599 patients with symptomatic heart
      failure to receive candesartan or placebo. The primary outcome comprised
      cardiovascular death or hospital admission for worsening heart failure. The
      relative risk (RR) conveyed by ECG LVH compared with a normal ECG was examined in
      a Cox model, adjusting for as many as 31 covariates of prognostic importance.
      RESULTS: The prevalence of ECG LVH was similar in all three CHARM trials
      (Alternative, 15.4%; Added, 17.1%; Preserved, 14.7%; Overall, 15.7%) despite a
      more frequent history of hypertension in CHARM-Preserved. ECG LVH was an
      independent predictor of worse prognosis in CHARM-Overall. RR for the primary
      outcome was 1.27 (95% confidence interval (CI) 1.04 to 1.55, p = 0.018). The risk
      of secondary end points was also increased: cardiovascular death, 1.50 (95% CI
      1.13 to 1.99, p = 0.005); hospitalisation due to heart failure, 1.19 (95% CI 0.94
      to 1.50, p = 0.148); and composite major cardiovascular events, 1.35 (95% CI 1.12
      to 1.62, p = 0.002). CONCLUSION: ECG LVH is similarly prevalent in patients with
      symptomatic heart failure regardless of LVEF. The simple clinical finding of ECG
      LVH was an independent predictor of a worse clinical outcome in a broad spectrum
      of patients with heart failure receiving extensive contemporary treatment.
      Candesartan had similar benefits in patients with and without ECG LVH.

PMID- 16952976
TI  - Relation between renal function within the normal range and central and
      peripheral arterial stiffness in hypertension.
AB  - Chronic kidney disease is accompanied by increased large-artery stiffness, but
      the relation between glomerular filtration rate within the reference range and
      central or peripheral arterial stiffness has been understudied. The link between
      renal function and arterial stiffness was assessed in 305 patients with never
      treated essential hypertension (men: 58%; age: 48+/-11 years, blood pressure:
      151/95+/-20/11 mm Hg), free from overt cardiovascular disease and with serum
      creatinine values <1.4 mg/dL (men) and <1.2 mg/dL (women), who underwent
      noninvasive aortic and upper-limb pulse wave velocity (PWV) determination. Aortic
      PWV was strongly related to age (r=0.55; P<0.001), whereas upper-limb PWV had a
      weaker nonlinear relation with age (beta=1.392; P<0.001 for age; beta=-1.312;
      P<0.001 for age squared) and a weak relation with aortic PWV (r=0.22; P<0.001).
      Glomerular filtration rate (GFR), estimated according to the Mayo clinic equation
      for healthy subjects, was inversely correlated with large-artery stiffness, as
      assessed by aortic PWV (r=-0.34; P<0.001), and with peripheral artery stiffness,
      as assessed by upper-limb PWV (r=-0.25; P<0.001). In a multivariate linear
      regression, aortic PWV was independently predicted by age (beta=0.48; P<0.001),
      mean arterial pressure (beta=0.14; P=0.013), and GFR (beta=-0.13, P=0.029). Upper
      limb PWV was predicted by GFR (beta=-0.24; P<0.001) and mean arterial pressure
      (beta=0.20; P<0.001). We conclude that, in hypertensive patients with normal
      renal function, an inverse relationship exists between GFR and stiffness of both
      central elastic and peripheral muscular arteries. These relations are in part
      independent from the effect of several confounders, including age, sex, and blood
      pressure values.

PMID- 16952977
TI  - Prediction of stroke by home "morning" versus "evening" blood pressure values:
      the Ohasama study.
AB  - Predictive power of self-measured blood pressure at home (home BP) for
      cardiovascular disease risk has been reported to be higher than casual-screening
      BP. However, the differential prognostic significance of home BP in the morning
      (morning BP) and in the evening (evening BP), respectively, has not been
      elucidated. In the Ohasama study, 1766 subjects (>or=40 years) were followed up
      for an average of 11 years. The predictive power for stroke incidence of evening
      BP was compared with that of morning BP as continuous variables. The Cox
      regression model demonstrated that evening BP and morning BP predicted future
      stroke risk equally. Subjects were also assigned to 1 of 4 categories based on
      home BP. In this analysis, stroke risk in morning hypertension ([HT] morning BP
      >or=135/85 mm Hg and evening BP <135/85 mm Hg; relative hazard (RH): 2.66; 95%
      CI:1.64 to 4.33) and that in sustained HT(morning BP and evening BP >or=135/85 mm
      Hg; RH: 2.38; 95% CI: 1.65 to 3.45) was significantly higher than that in
      normotension (morning BP and evening BP <135/85 mm Hg). The risk in morning HT
      was more remarkable in subjects taking antihypertensive medication (RH: 3.55; 95%
      CI: 1.70 to 7.38). Although the risk in evening HT (morning BP <135/85 mm Hg and
      evening BP >or=135/85 mm Hg) was higher than that in normotension, the
      differences were not significant. In conclusion, morning BP and evening BP
      provide equally useful information for stroke risk, whereas morning HT, which
      indicates HT specifically observed in the morning, might be a good predictor of
      stroke, particularly among individuals using anti-HT medication.

PMID- 16952978
TI  - Mechanisms of diabetic nephropathy: role of hypertension.

PMID- 16952979
TI  - Foxo transcription factors blunt cardiac hypertrophy by inhibiting calcineurin
      signaling.
AB  - BACKGROUND: Cellular hypertrophy requires coordinated regulation of progrowth and
      antigrowth mechanisms. In cultured neonatal cardiomyocytes, Foxo transcription
      factors trigger an atrophy-related gene program that counters hypertrophic
      growth. However, downstream molecular events are not yet well defined. METHODS
      AND RESULTS: Here, we report that expression of either Foxo1 or Foxo3 in
      cardiomyocytes attenuates calcineurin phosphatase activity and inhibits agonist
      induced hypertrophic growth. Consistent with these results, Foxo proteins
      decrease calcineurin phosphatase activity and repress both basal and hypertrophic
      agonist-induced expression of MCIP1.4, a direct downstream target of the
      calcineurin/NFAT pathway. Furthermore, hearts from Foxo3-null mice exhibit
      increased MCIP1.4 abundance and a hypertrophic phenotype with normal systolic
      function at baseline. Together, these results suggest that Foxo proteins repress
      cardiac growth at least in part through inhibition of the calcineurin/NFAT
      pathway. Given that hypertrophic growth of the heart occurs in multiple contexts,
      our findings also suggest that certain hypertrophic signals are capable of
      overriding the antigrowth program induced by Foxo. Consistent with this, multiple
      hypertrophic agonists triggered inactivation of Foxo proteins in cardiomyocytes
      through a mechanism requiring the PI3K/Akt pathway. In addition, both Foxo1 and
      Foxo3 are phosphorylated and consequently inactivated in hearts undergoing
      hypertrophic growth induced by hemodynamic stress. CONCLUSIONS: This study
      suggests that inhibition of the calcineurin/NFAT signaling cascade by Foxo and
      release of this repressive action by the PI3K/Akt pathway are important
      mechanisms whereby Foxo factors govern cell growth in the heart.

PMID- 16952980
TI  - Transcriptional genomics associates FOX transcription factors with human heart
      failure.
AB  - BACKGROUND: Specific transcription factors (TFs) modulate cardiac gene expression
      in murine models of heart failure, but their relevance in human subjects remains
      untested. We developed and applied a computational approach called
      transcriptional genomics to test the hypothesis that a discrete set of cardiac
      TFs is associated with human heart failure. METHODS AND RESULTS: RNA isolates
      from failing (n=196) and nonfailing (n=16) human hearts were hybridized with
      Affymetrix HU133A arrays, and differentially expressed heart failure genes were
      determined. TF binding sites overrepresented in the -5-kb promoter sequences of
      these heart failure genes were then determined with the use of public genome
      sequence databases. Binding sites for TFs identified in murine heart failure
      models (MEF2, NKX, NF-AT, and GATA) were significantly overrepresented in
      promoters of human heart failure genes (P<0.002; false discovery rate 2% to 4%).
      In addition, binding sites for FOX TFs showed substantial overrepresentation in
      both advanced human and early murine heart failure (P<0.002 and false discovery
      rate <4% for each). A role for FOX TFs was supported further by expression of
      FOXC1, C2, P1, P4, and O1A in failing human cardiac myocytes at levels similar to
      established hypertrophic TFs and by abundant FOXP1 protein in failing human
      cardiac myocyte nuclei. CONCLUSIONS: Our results provide the first evidence that
      specific TFs identified in murine models (MEF2, NKX, NFAT, and GATA) are
      associated with human heart failure. Moreover, these data implicate specific
      members of the FOX family of TFs (FOXC1, C2, P1, P4, and O1A) not previously
      suggested in heart failure pathogenesis. These findings provide a crucial link
      between animal models and human disease and suggest a specific role for FOX
      signaling in modulating the hypertrophic response of the heart to stress in
      humans.

PMID- 16952981
TI  - Identification of the oxidized low-density lipoprotein scavenger receptor CD36 in
      plasma: a novel marker of insulin resistance.
AB  - BACKGROUND: Macrophage CD36 scavenges oxidized low-density lipoprotein, leading
      to foam cell formation, and appears to be a key proatherogenic molecule.
      Increased expression of CD36 has been attributed to hyperglycemia and to
      defective macrophage insulin signaling in insulin resistance. Premature
      atherosclerosis is the major cause of morbidity and mortality in type 2 diabetes.
      Here, we report the identification of a soluble form of CD36 (sCD36) in plasma
      and hypothesize that sCD36 would be elevated in patients with type 2 diabetes and
      insulin resistance. METHODS AND RESULTS: sCD36 in plasma was demonstrated by
      immunopurification and Western blotting. We established ELISA assays to determine
      sCD36 in plasma and measured sCD36 in obese type 2 diabetic patients, obese
      nondiabetic relatives, and obese and lean control subjects. sCD36 was markedly
      elevated in type 2 diabetic patients compared with both lean (5-fold) and obese
      (2- to 3-fold) control subjects. There was a strong, inverse correlation between
      sCD36 and insulin-stimulated glucose disposal and a direct correlation with
      fasting plasma glucose, fasting insulin, and body mass index. CONCLUSIONS: Our
      study demonstrates sCD36 in plasma for the first time. sCD36 is highly related to
      risk factors of accelerated atherosclerosis in type 2 diabetes such as insulin
      resistance and glycemic control, and we propose that sCD36 might represent a
      marker of the metabolic syndrome and a potential surrogate marker of
      atherosclerosis.

PMID- 16952982
TI  - Cardiac S100A1 protein levels determine contractile performance and propensity
      toward heart failure after myocardial infarction.
AB  - BACKGROUND: Diminished cardiac S100A1 protein levels are characteristic of
      ischemic and dilated human cardiomyopathy. Because S100A1 has recently been
      identified as a Ca2+-dependent inotropic factor in the heart, this study sought
      to explore the pathophysiological relevance of S100A1 levels in development and
      progression of postischemic heart failure (HF). METHODS AND RESULTS: S100A1
      transgenic (STG) and S100A1-knockout (SKO) mice were subjected to myocardial
      infarction (MI) by surgical left anterior descending coronary artery ligation,
      and survival, cardiac function, and remodeling were compared with nontransgenic
      littermate control (NLC) and wild-type (WT) animals up to 4 weeks. Although MI
      size was similar in all groups, infarcted S100A1-deficient hearts (SKO-MI)
      responded with acute contractile decompensation and accelerated transition to HF,
      rapid onset of cardiac remodeling with augmented apoptosis, and excessive
      mortality. NLC/WT-MI mice, displaying a progressive decrease in cardiac S100A1
      expression, showed a later onset of cardiac remodeling and progression to HF.
      Infarcted S100A1-overexpressing hearts (STG-MI), however, showed preserved global
      contractile performance, abrogated apoptosis, and prevention from cardiac
      hypertrophy and HF with superior survival compared with NLC/WT-MI and SKO-MI.
      Both Gq-protein-dependent signaling and protein kinase C activation resulted in
      decreased cardiac S100A1 mRNA and protein levels, whereas Gs-protein-related
      signaling exerted opposite effects on cardiac S100A1 abundance. Mechanistically,
      sarcoplasmic reticulum Ca2+ cycling and beta-adrenergic signaling were severely
      impaired in SKO-MI myocardium but preserved in STG-MI. CONCLUSIONS: Our novel
      proof-of-concept study provides evidence that downregulation of S100A1 protein
      critically contributes to contractile dysfunction of the diseased heart, which is
      potentially responsible for driving the progressive downhill clinical course of
      patients with HF.

PMID- 16952983
TI  - How sudden is sudden cardiac death?
AB  - BACKGROUND: Out-of-hospital sudden cardiac death (SCD) is a frequent cause of
      death. Survival rates remain low despite increasing efforts in medical care.
      Better understanding of the circumstances of SCD could be helpful in developing
      preventive measures and facilitating proper reactions to such a pending event.
      METHODS AND RESULTS: Information on cases of out-of-hospital SCD was collected in
      the Berlin, Germany, emergency medical system via a questionnaire. Bystander
      interviews were performed by the emergency physician on scene immediately after
      declaration of death or return of circulation. Of 5831 rescue missions, 406
      involved patients with presumed cardiac arrest. Sixty-six percent had a known
      cardiac disease. In 72%, the arrest occurred at home, and in 67%, it occurred in
      the presence of an eyewitness. Information on symptoms immediately preceding the
      arrest was available in 80% (n = 323) of all 406 patients and in 274 of those
      with witnessed arrest. Symptoms were identical in the 2 groups. Typical angina
      was present for a median of 120 minutes in 25% of the 274 patients with witnessed
      arrest and in 33% with a symptom duration of less than 1 hour. CONCLUSIONS: SCD
      occurs most often at home in the presence of relatives and after a longer period
      of typical warning symptoms. Although the much-hailed use of public access
      defibrillation is supported by several studies, the present results raise the
      question of whether educational measures and targeted educational programs
      tailored for patients at risk and their relatives should have a higher priority.

PMID- 16952984
TI  - Altered creatine kinase adenosine triphosphate kinetics in failing hypertrophied
      human myocardium.
AB  - BACKGROUND: The progression of pressure-overload left ventricular hypertrophy
      (LVH) to chronic heart failure (CHF) may involve a relative deficit in energy
      supply and/or delivery. METHODS AND RESULTS: We measured myocardial creatine
      kinase (CK) metabolite concentrations and adenosine triphosphate (ATP) synthesis
      through CK, the primary energy reserve of the heart, to test the hypothesis that
      ATP flux through CK is impaired in patients with LVH and CHF. Myocardial ATP
      levels were normal, but creatine phosphate levels were 35% lower in LVH patients
      (n = 10) than in normal subjects (n = 14, P < 0.006). Left ventricular mass and
      CK metabolite levels in LVH were not different from those in patients with LVH
      and heart failure (LVH+CHF, n = 10); however, the myocardial CK pseudo first
      order rate constant was normal in LVH (0.36 +/- 0.04 s(-1) in LVH versus 0.32 +/-
      0.06 s(-1) in normal subjects) but halved in LVH+CHF (0.17 +/- 0.06 s(-1), P <
      0.001). The net ATP flux through CK was significantly reduced by 30% in LVH (2.2
      +/- 0.7 micromol x g(-1) x s(-1), P = 0.011) and by a dramatic 65% in LVH+CHF
      (1.1 +/- 0.4 micromol x g(-1) x s(-1), P < 0.001) compared with normal subjects
      (3.1 +/- 0.8 micromol x g(-1) x s(-1)). CONCLUSIONS: These first observations in
      human LVH demonstrate that it is not the relative or absolute CK metabolite pool
      sizes but rather the kinetics of ATP turnover through CK that distinguish failing
      from nonfailing hypertrophic hearts. Moreover, the deficit in ATP kinetics is
      similar in systolic and nonsystolic heart failure and is not related to the
      severity of hypertrophy but to the presence of CHF. Because CK temporally buffers
      ATP, these observations support the hypothesis that a deficit in myofibrillar
      energy delivery contributes to CHF pathophysiology in human LVH.

PMID- 16952985
TI  - A taxonomy for disease management: a scientific statement from the American Heart
      Association Disease Management Taxonomy Writing Group.
AB  - BACKGROUND: Disease management has shown great promise as a means of reorganizing
      chronic care and optimizing patient outcomes. Nevertheless, disease management
      programs are widely heterogeneous and lack a shared definition of disease
      management, which limits our ability to compare and evaluate different programs.
      To address this problem, the American Heart Association's Disease Management
      Taxonomy Writing Group developed a system of classification that can be used both
      to categorize and compare disease management programs and to inform efforts to
      identify specific factors associated with effectiveness. METHODS: The AHA Writing
      Group began with a conceptual model of disease management and its components and
      subsequently validated this model over a wide range of disease management
      programs. A systematic MEDLINE search was performed on the terms heart failure,
      diabetes, and depression, together with disease management, case management, and
      care management. The search encompassed articles published in English between
      1987 and 2005. We then selected studies that incorporated (1) interventions
      designed to improve outcomes and/or reduce medical resource utilization in
      patients with heart failure, diabetes, or depression and (2) clearly defined
      protocols with at least 2 prespecified components traditionally associated with
      disease management. We analyzed the study protocols and used qualitative research
      methods to develop a disease management taxonomy with our conceptual model as the
      organizing framework. RESULTS: The final taxonomy includes the following 8
      domains: (1) Patient population is characterized by risk status, demographic
      profile, and level of comorbidity. (2) Intervention recipient describes the
      primary targets of disease management intervention and includes patients and
      caregivers, physicians and allied healthcare providers, and healthcare delivery
      systems. (3) Intervention content delineates individual components, such as
      patient education, medication management, peer support, or some form of postacute
      care, that are included in disease management. (4) Delivery personnel describes
      the network of healthcare providers involved in the delivery of disease
      management interventions, including nurses, case managers, physicians,
      pharmacists, case workers, dietitians, physical therapists, psychologists, and
      information systems specialists. (5) Method of communication identifies a broad
      range of disease management delivery systems that may include in-person
      visitation, audiovisual information packets, and some form of electronic or
      telecommunication technology. (6) Intensity and complexity distinguish between
      the frequency and duration of exposure, as well as the mix of program components,
      with respect to the target for disease management. (7) Environment defines the
      context in which disease management interventions are typically delivered and
      includes inpatient or hospital-affiliated outpatient programs, community or home
      based programs, or some combination of these factors. (8) Clinical outcomes
      include traditional, frequently assessed primary and secondary outcomes, as well
      as patient-centered measures, such as adherence to medication, self-management,
      and caregiver burden. CONCLUSIONS: This statement presents a taxonomy for disease
      management that describes critical program attributes and allows for comparisons
      across interventions. Routine application of the taxonomy may facilitate better
      comparisons of structure, process, and outcome measures across a range of disease
      management programs and should promote uniformity in the design and conduct of
      studies that seek to validate disease management strategies.

PMID- 16952986
TI  - Transfection of human hepatocyte growth factor gene ameliorates secondary
      lymphedema via promotion of lymphangiogenesis.
AB  - BACKGROUND: Lymphedema is a disorder of the lymphatic vascular system
      characterized by impaired lymphatic return and swelling of the extremities.
      Treatment for this disabling condition remains limited and largely ineffective.
      The goal of the present study was to investigate the therapeutic efficacy of
      hepatocyte growth factor (HGF) in animal models of lymphedema. METHODS AND
      RESULTS: Immunofluorescent analysis demonstrated that canine primary lymphatic
      endothelial cells (cLECs) were positive for lymphatic-specific markers (vascular
      endothelial growth factor receptor-3, LYVE-1, podoplanin, and Prox1) and the HGF
      receptor c-Met. Treating cLECs with human recombinant HGF resulted in a dose
      dependent increase in cell growth and migration and increased activity of
      extracellular signal-regulated kinase and Akt. In human LECs, c-Met also was
      expressed, and treatment with HGF increased cell growth and migration in a dose
      dependent manner. Transfection of human HGF plasmid DNA in cLECs also increased
      the c-fos promoter activity. Furthermore, weekly HGF gene transfer in a rat tail
      lymphedema model by disruption of lymphatic vessels resulted in a decrease in
      lymphedema thickness. Although expression of the endothelial cell marker PECAM-1
      was increased in both HGF- and vascular endothelial growth factor 165-injected
      groups, expression of LEC markers (LYVE-1 and Prox1) was increased only in the
      HGF-injected group. CONCLUSIONS: These data demonstrate that expression of HGF
      via plasmid transfer improves lymphedema via promotion of lymphangiogenesis.
      Further studies to determine the clinical utility of this approach would be of
      benefit to patients with lymphedema.

PMID- 16952988
TI  - Images in cardiovascular medicine. Scimitar syndrome: complete diagnosis by
      transthoracic echocardiography.

PMID- 16952987
TI  - Rheumatoid arthritis is associated with increased aortic pulse-wave velocity,
      which is reduced by anti-tumor necrosis factor-alpha therapy.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is associated with increased cardiovascular
      risk, which is not explained by traditional cardiovascular risk factors but may
      be due in part to increased aortic stiffness, an independent predictor of
      cardiovascular mortality. In the present study, our aim was to establish whether
      aortic stiffness is increased in RA and to investigate the relationship between
      inflammation and aortic stiffness. In addition, we tested the hypothesis that
      aortic stiffness could be reduced with anti-tumor necrosis factor-alpha (TNF
      alpha) therapy. METHODS AND RESULTS: Aortic pulse-wave velocity (PWV),
      augmentation index, and blood pressure were measured in 77 patients with RA and
      in 142 healthy individuals. Both acute and chronic inflammatory measures and
      disease activity were determined. The effect of anti-TNF-alpha therapy on PWV and
      endothelial function was measured in 9 RA patients at 0, 4, and 12 weeks. Median
      (interquartile range) aortic PWV was significantly higher in subjects with RA
      than in control subjects (8.35 [7.14 to 10.24] versus 7.52 [6.56 to 9.18] m/s,
      respectively; P = 0.005). In multiple regression analyses, aortic PWV correlated
      independently with age, mean arterial pressure, and log-transformed C-reactive
      protein (R2 = 0.701; P < 0.0001). Aortic PWV was reduced significantly by anti
      TNF-alpha therapy (8.82+/-2.04 versus 7.94+/-1.86 versus 7.68+/-1.56 m/s at weeks
      0, 4, and 12, respectively; P < 0.001); concomitantly, endothelial function
      improved. CONCLUSIONS: RA is associated with increased aortic stiffness, which
      correlates with current but not historical measures of inflammation, suggesting
      that increased aortic stiffness may be reversible. Indeed, anti-TNF-alpha therapy
      reduced aortic stiffness to a level comparable to that of healthy individuals.
      Therefore, effective control of inflammation may be of benefit in reducing
      cardiovascular risk in patients with RA.

PMID- 16952989
TI  - Images in cardiovascular medicine. Myocardial fibroma in gorlin syndrome by
      cardiac magnetic resonance imaging.

PMID- 16952990
TI  - Images in cardiovascular medicine. Large pulmonary artery aneurysm rupture in
      Hughes-Stovin syndrome: multidetector computed tomography pattern and
      endovascular treatment.

PMID- 16952991
TI  - Letter by Struthers et al regarding article, "cross-sectional relations of
      multiple biomarkers from distinct biological pathways to brachial artery
      endothelial function".

PMID- 16952992
TI  - Viewpoint: genetics and arrhythmias.

PMID- 16952993
TI  - A paradigm shift in cardiac pacing therapy?

PMID- 16952994
TI  - New cholesterol guidelines for children?

PMID- 16952995
TI  - Protease-activated receptors in cardiovascular diseases.
AB  - Thrombosis associated with the pathophysiological activation of platelets and
      vascular cells has brought thrombin and its receptors to the forefront of
      cardiovascular medicine. Thrombin signaling through the protease-activated
      receptors (PARs) has been shown to influence a wide range of physiological
      responses including platelet activation, intimal hyperplasia, inflammation, and
      maintenance of vascular tone and barrier function. The thrombin receptors PAR1
      and PAR4 can be effectively targeted in animals in which acute or prolonged
      exposure to thrombin leads to thrombosis and/or restenosis. In the present study,
      we describe the molecular and pharmacological basis of small-molecule inhibitors
      that target PAR1. In addition, we discuss a new class of cell-penetrating
      inhibitors, termed pepducins, that provide insight into previously unidentified
      roles of PAR1 and PAR4 in protease signaling.

PMID- 16952996
TI  - Hypothesis testing: means.

PMID- 16952997
TI  - The Scat Players.

PMID- 16952998
TI  - Gamma-aminobutyric acid type A receptors and alcoholism: intoxication,
      dependence, vulnerability, and treatment.
AB  - CONTEXT: Alcohol facilitates gamma-aminobutyric acid (GABA) function, and GABA
      type A (GABA(A)) receptor-facilitating agents suppress alcohol withdrawal
      symptoms. Advances in molecular neuroscience, genetics, and neuroimaging provide
      new insights into the role of brain GABA systems in short- and long-term alcohol
      effects. OBJECTIVE: To review the role of brain GABA systems in alcohol response,
      alcohol dependence, alcoholism vulnerability, and alcoholism pharmacotherapy.
      DESIGN: Literature review. RESULTS: Alcohol increases GABA release, raises
      neurosteroid levels, and may potently enhance the function of a GABA(A) receptor
      subclass that shows high affinity for GABA and neurosteroids, relative
      insensitivity to benzodiazepines, low chloride conductance, and an extrasynaptic
      location. Variation in GABA(A) receptor subunit genes may contribute to the
      vulnerability to alcoholism, particularly in the context of environmental risk
      factors. Alcohol dependence is associated with time-dependent changes in brain
      GABA(A) receptor density and subunit gene expression levels that contribute to a
      withdrawal-related deficit in GABA(A) receptor function. However, cortical GABA
      levels are not reduced during acute withdrawal. Benzodiazepine-assisted
      detoxification enhances a phasic component of GABA function. However, novel
      treatments target the tonic component of GABA neurotransmission mediated by
      benzodiazepine-insensitive GABA(A) receptors. Smoking attenuates withdrawal
      related disturbances in brain GABA function, perhaps contributing to comorbid
      nicotine and alcohol dependence. The GABA systems show recovery with long-term
      sobriety. CONCLUSIONS: Recent research deepens our understanding of the role of
      GABA systems in alcohol action, alcohol dependence, and the vulnerability to
      alcoholism. Also, GABA(A) receptor subtype-selective treatments merit exploration
      for reducing withdrawal symptoms and drinking in alcohol-dependent individuals.

PMID- 16952999
TI  - Prediction of functional outcome 18 months after a first psychotic episode: a
      proton magnetic resonance spectroscopy study.
AB  - CONTEXT: Recent magnetic resonance imaging studies have attempted to relate
      volumetric brain measurements in early schizophrenia to clinical and functional
      outcome some years later. These studies have generally been negative, perhaps
      because gray and white matter volumes inaccurately assess the underlying
      dysfunction that might be predictive of outcome. OBJECTIVE: To investigate the
      predictive value of frontal and temporal spectroscopy measures for outcome in
      patients with first-episode psychoses. DESIGN: Left prefrontal cortex and left
      mediotemporal lobe voxels were assessed using proton magnetic resonance
      spectroscopy to provide the ratio of N-acetylaspartate (NAA) and choline
      containing compounds to creatine and phosphocreatine (Cr) (NAA/Cr ratio). These
      data were used to predict outcome at 18 months after admission, as assessed by a
      systematic medical record audit. SETTING: Early psychosis clinic. PARTICIPANTS:
      Forty-six patients with first-episode psychosis. MAIN OUTCOME MEASURES: We used
      regression models that included age at imaging and duration of untreated
      psychosis to predict outcome scores on the Global Assessment of Functioning
      Scale, Clinical Global Impression scales, and Social and Occupational Functional
      Assessment Scale, as well as the number of admissions during the treatment
      period. We then further considered the contributions of premorbid function and
      baseline level of negative symptoms. RESULTS: The only spectroscopic predictor of
      outcome was the NAA/Cr ratio in the prefrontal cortex. Low scores on this
      variable were related to poorer outcome on all measures. In addition, the frontal
      NAA/Cr ratio explained 17% to 30% of the variance in outcome. CONCLUSIONS:
      Prefrontal neuronal dysfunction is an inconsistent feature of early psychosis;
      rather, it is an early marker of poor prognosis across the first years of
      illness. The extent to which this can be used to guide treatment and whether it
      predicts outcome some years after first presentation are questions for further
      research.

PMID- 16953000
TI  - Differential effects of 5-HTTLPR genotypes on the behavioral and neural responses
      to tryptophan depletion in patients with major depression and controls.
AB  - CONTEXT: Tryptophan depletion (TD) is a model used to study the contribution of
      reduced serotonin transmission to the pathogenesis of major depressive disorder
      (MDD). Recent studies have not sufficiently addressed the relative contribution
      of a functional-length triallelic polymorphism in the promoter of the serotonin
      transporter, 5-HTTLPR, to the behavioral and neural responses to TD in
      individuals with remitted MDD (rMDD) and controls. OBJECTIVE: To determine the
      role of 5-HTTLPR on the behavioral and neural responses to TD in medication-free
      patients with rMDD and individually matched controls. DESIGN: Participants were
      stratified according to diagnosis and 5-HTTLPR genotypes and underwent TD on one
      test day and sham depletion on the other test day in a prospective, double-blind,
      randomized order. SETTING: Outpatient clinic. PARTICIPANTS: Twenty-seven
      medication-free patients with rMDD (18 women and 9 men) and 26 controls (17 women
      and 9 men). INTERVENTIONS: Tryptophan depletion was induced by administration of
      capsules containing an amino acid mixture without tryptophan. Sham depletion used
      identical capsules containing lactose. Fludeoxyglucose F 18 positron emission
      tomography was performed 6 hours after TD. Magnetic resonance images were
      obtained for each participant. MAIN OUTCOME MEASURES: Quantitative positron
      emission tomography of regional cerebral metabolic rates for glucose and measures
      of depression using the Hamilton Depression Rating Scale. RESULTS: Behavioral
      responses to TD are affected by 5-HTTLPR in patients with rMDD and controls. A
      direct effect of 5-HTTLPR on the regulation of regional cerebral metabolic rates
      for glucose was identified in patients with rMDD for the amygdala, hippocampus,
      and subgenual anterior cingulate cortex. CONCLUSIONS: Variations in 5-HTTLPR
      modulate the sensitivity of patients with rMDD and controls to the behavioral
      effects of TD. In patients with rMDD, variations in triallelic 5-HTTLPR have a
      direct effect on regulation of regional cerebral metabolic rates for glucose in a
      corticolimbic circuit that has been implicated in rMDD.

PMID- 16953001
TI  - Stress-related negative affectivity and genetically altered serotonin transporter
      function: evidence of synergism in shaping risk of depression.
AB  - CONTEXT: Genetic moderation of the depression-inducing effects of stressful life
      events (SLEs) has been reported, but findings suggest that genes may not moderate
      the effects of SLEs per se but instead may moderate the risk of depression
      associated with the stable tendency to develop negative emotions in response to
      minor environmental experiences. OBJECTIVE: To examine whether a functional
      polymorphism of the serotonin transporter gene (5-HTTLPR) moderates the
      association between negative affectivity (neuroticism) and depression and to what
      degree this can explain previous findings involving SLEs. DESIGN: A prospective
      cohort study involving 1 baseline and 4 follow-up measurements in 15 months
      analyzing change in self-reported depressive symptoms across time as a function
      of negatively attributed SLEs, neuroticism, 5-HTTLPR, and their interactions.
      SETTING: General community. PARTICIPANTS: A population-based sample of 374
      ethnically homogeneous young adult female twins. MAIN OUTCOME MEASURE: A
      continuous score of self-reported depressive symptoms. RESULTS: The depressogenic
      effect of SLEs in the 3 months before interview was significantly greater in
      women with 2 short (S) alleles compared with women with 1 or none. However, this
      effect disappeared after accounting for the effect of SLEs conditional on
      neuroticism. Similarly, the depressogenic effect of neuroticism was progressively
      greater with number of S alleles, and this was unchanged after accounting for the
      effect of neuroticism conditional on SLEs. CONCLUSIONS: Genotype x environment
      interactions in depression may be more productively interpreted by involving
      mechanisms more proximal to psychological experience itself. The probability that
      stress-related cognitive vulnerabilities for depression result in symptom
      formation may be moderated by a neurobiologic phenotype characterized by altered
      processing of negative emotions associated with variation in 5-HTTLPR.

PMID- 16953002
TI  - High levels of dopamine D2 receptors in unaffected members of alcoholic families:
      possible protective factors.
AB  - CONTEXT: Predisposition to alcoholism is likely an interaction between genetic
      and environmental factors that confer vulnerability and protection. Alcoholic
      subjects have low levels of dopamine D(2) receptors in striatum, and increasing
      D(2) receptor levels in laboratory animals reduces alcohol consumption.
      OBJECTIVES: To test whether high levels of D(2) receptors may be protective
      against alcoholism and whether this is mediated by their modulation of activity
      in orbitofrontal cortex and cingulate gyrus (regions involved in salience
      attribution, emotional reactivity, and inhibitory control). DESIGN: Research
      (nonalcoholic subjects with a family history of alcoholism) and comparison
      (nonalcoholic subjects with a negative family history) sample. SETTING:
      Outpatient setting. PARTICIPANTS: Fifteen nonalcoholic subjects who had an
      alcoholic father and at least 2 other first- or second-degree relatives who were
      alcoholics (family-positive group) and 16 nonalcoholic controls with no family
      history of alcoholism (family-negative group). MAIN OUTCOME MEASURES: Results of
      positron emission tomography with raclopride C 11 to assess D(2) receptors and
      with fludeoxyglucose F 18 to assess brain glucose metabolism (marker of brain
      function). Personality measures were obtained with the Multidimensional
      Personality Questionnaire. RESULTS: Availability of D(2) receptors was
      significantly higher in caudate and ventral striatum in family-positive than
      family-negative subjects. In family-positive but not family-negative subjects,
      striatal D(2) receptors were associated with metabolism in anterior cingulate
      (Brodmann area 24/25) and orbitofrontal (Brodmann area 11) and prefrontal
      (Brodmann area 9/10) cortices, and with personality scores of positive
      emotionality. CONCLUSIONS: The higher-than-normal D(2) receptor availability in
      nonalcoholic members of alcoholic families supports the hypothesis that high
      levels of D(2) receptors may protect against alcoholism. The significant
      associations between D(2) receptors and metabolism in frontal regions involved
      with emotional reactivity and executive control suggest that high levels of D(2)
      receptors could protect against alcoholism by regulating circuits involved in
      inhibiting behavioral responses and in controlling emotions.

PMID- 16953003
TI  - In utero alcohol exposure and prediction of alcohol disorders in early adulthood:
      a birth cohort study.
AB  - CONTEXT: Little is known about the contribution of fetal alcohol exposure to the
      development of alcohol disorders in early adulthood. OBJECTIVE: To examine the
      independent effect of maternal alcohol use during early vs late periods in
      pregnancy on the time of onset of alcohol disorders in offspring. DESIGN: Follow
      up study of the Mater-University of Queensland Study of Pregnancy and Its
      Outcomes (MUSP), a population-based birth cohort study commenced in Brisbane,
      Australia, in 1981 and designed to examine the association of maternal alcohol
      exposure with the onset of alcohol disorders. Mothers and children were followed
      up at birth, 6 months, and 5, 14, and 21 years after the initial interview.
      Maternal alcohol use was assessed before pregnancy, in early and late pregnancy,
      and at the 5- and 14-year follow-up visits. Alcohol disorders in early adulthood
      were assessed at age 21 years using the lifetime version of the Composite
      International Diagnostic Interview-computerized version. SETTING: Population
      based birth cohort study. PARTICIPANTS: A subsample of 2138 participants for whom
      complete data were available at the 21-year follow-up. MAIN OUTCOME MEASURE:
      Onset of alcohol disorder from adolescence to 21 years of age. RESULTS: In utero
      alcohol exposure of 3 or more glasses was associated with alcohol disorders. The
      fully adjusted odds ratios (95% confidence intervals) of developing early-onset
      alcohol disorders at age 21 years were 2.95 (1.62-5.36) for those exposed to
      maternal drinking in early pregnancy and 1.35 (0.69-2.63) for those exposed in
      late pregnancy. There was also a strong association between alcohol exposure in
      early pregnancy and late-onset alcohol disorders (odds ratio, 3.29 [95%
      confidence interval, 1.74-6.24]). CONCLUSIONS: Our results provide support for a
      biological origin of adult alcohol disorders and suggest that the association is
      not explained solely by maternal drinking or smoking during childhood and
      adolescence or other intervening factors. Further research is needed to
      understand the mechanisms underlying the association.

PMID- 16953004
TI  - Proximal psychiatric risk factors for suicidality in youth: the Great Smoky
      Mountains Study.
AB  - CONTEXT: Psychiatric disorder is a major risk factor for suicidality but has poor
      positive predictive value. OBJECTIVES: To characterize proximal risks for
      suicidality associated with anxiety, depressive, disruptive behavior, and
      substance use disorders, and to test whether there are critical combinations of
      disorders that discriminate at-risk youth independent of severity of
      psychopathology. DESIGN: The Great Smoky Mountains Study, a representative sample
      of children and adolescents aged 9 to 16 years from the southeastern United
      States. Subjects and their parents were interviewed on multiple occasions from
      1993 to 2000 about the subjects' recent psychiatric and suicidal history.
      SETTING: An epidemiological sample of youth. PARTICIPANTS: The sample included
      1420 individual subjects with 6676 records across 8 waves of data collection.
      MAIN OUTCOME MEASURES: Wanting to die, suicidal ideation, suicide plans, or
      suicide attempt during the past 3 months. RESULTS: Eleven broad psychiatric
      profiles discriminated suicidal youth. Risk was greatest in association with
      current depression plus anxiety (specifically GAD [generalized anxiety disorder])
      (odds ratio, 468.53) or depression plus a disruptive disorder (primarily ODD
      [oppositional-defiant disorder]) (odds ratio, 222.94). Unless comorbid, anxiety
      and substance use disorders were not proximally associated with suicidality. The
      severity of symptom-related impairment and, in some cases, total symptom load
      explained risk associated with all psychiatric profiles except depression plus
      anxiety, specifically GAD (adjusted odds ratio, 50.16). Severity of impairment
      and poverty defined by federal guidelines for families were both independent risk
      factors, irrespective of psychiatric profile. Suicidal youth without diagnosable
      disorders had subthreshold (mostly disruptive) disorders, disabling relationship
      difficulties, or psychiatric symptoms without associated impairment. CONCLUSIONS:
      Severity of symptom-related impairment and total symptom load explained most of
      the risk for suicidality associated with current psychiatric disorders. Only
      depression plus GAD discriminated at-risk youth independent of severity of
      psychopathology.

PMID- 16953005
TI  - Advancing paternal age and autism.
AB  - CONTEXT: Maternal and paternal ages are associated with neurodevelopmental
      disorders. OBJECTIVE: To examine the relationship between advancing paternal age
      at birth of offspring and their risk of autism spectrum disorder (ASD). DESIGN:
      Historical population-based cohort study. SETTING: Identification of ASD cases
      from the Israeli draft board medical registry. PARTICIPANTS: We conducted a study
      of Jewish persons born in Israel during 6 consecutive years. Virtually all men
      and about three quarters of women in this cohort underwent draft board assessment
      at age 17 years. Paternal age at birth was obtained for most of the cohort;
      maternal age was obtained for a smaller subset. We used the smaller subset (n =
      132 271) with data on both paternal and maternal age for the primary analysis and
      the larger subset (n = 318 506) with data on paternal but not maternal age for
      sensitivity analyses. MAIN OUTCOME MEASURES: Information on persons coded as
      having International Classification of Diseases, 10th Revision ASD was obtained
      from the registry. The registry identified 110 cases of ASD (incidence, 8.3 cases
      per 10 000 persons), mainly autism, in the smaller subset with complete parental
      age data. RESULTS: There was a significant monotonic association between
      advancing paternal age and risk of ASD. Offspring of men 40 years or older were
      5.75 times (95% confidence interval, 2.65-12.46; P<.001) more likely to have ASD
      compared with offspring of men younger than 30 years, after controlling for year
      of birth, socioeconomic status, and maternal age. Advancing maternal age showed
      no association with ASD after adjusting for paternal age. Sensitivity analyses
      indicated that these findings were not the result of bias due to missing data on
      maternal age. CONCLUSIONS: Advanced paternal age was associated with increased
      risk of ASD. Possible biological mechanisms include de novo mutations associated
      with advancing age or alterations in genetic imprinting.

PMID- 16953006
TI  - School bullying and youth violence: causes or consequences of psychopathologic
      behavior?
AB  - CONTEXT: The causal relation between school bullying and psychopathologic
      behavior has been the focus of substantial debate. Previous studies have failed
      to garner causal evidence in either direction, largely because of methodologic
      constraints such as cross-sectional study designs, shared method variance, and
      analytic shortfalls. OBJECTIVE: To determine the direction of the causal relation
      between psychopathologic behavior and school bullying. DESIGN: Prospective cohort
      study. SETTING: Two Korean middle schools. PARTICIPANTS: A total of 1655 seventh-
      and eighth-grade students were studied between 2000 and 2001. MAIN OUTCOME
      MEASURES: School bullying was assessed by peer nomination, and 7 subscales of the
      Korean Youth Self Report were used to identify symptoms of psychopathologic
      behaviors. School bullying was categorized into 4 groups: victims, perpetrators,
      victim-perpetrators, and neither. A T-score on the Korean Youth Self Report
      greater than 65 was regarded as a clinically significant indicator. RESULTS:
      Social problems increased the risk of becoming a victim or a victim-perpetrator
      (odds ratio [OR], 2.3 and 2.7, respectively), and these associations disappeared
      when baseline bullying status was adjusted. Ten months later, individuals who
      were victims at baseline showed increased risk of social problems (OR, 3.9),
      those who were perpetrators had increased aggression (OR, 1.8), and victim
      perpetrators had increased aggression and externalizing problems (OR, 4.9 and
      4.6, respectively). Analyses that examined exposure history provided additional
      evidence for the causal effect of bullying experience on the later development of
      psychopathologic behaviors because most forms of psychopathologic behavior that
      led to new-onset bullying at follow-up were also present at follow-up, making it
      impossible to distinguish the temporal sequence of these variables and their
      causal relationship. However, most forms of new-onset psychopathologic behaviors
      at follow-up were associated with antecedent bullying experience. CONCLUSIONS:
      Our study results support the conclusion that psychopathologic behavior,
      including social problems, aggression, and externalizing behavioral problems, is
      a consequence rather than a cause of bullying experiences. This causal relation
      is supported by the strength and specificity of the association and the temporal
      antecedence of bullying. Because school bullying is a known correlate of youth
      violence, such a finding adds greater urgency to the search for programs to
      prevent or diminish bullying among schoolchildren.

PMID- 16953007
TI  - Psychological well-being and relationship outcomes in a randomized study of
      family-led education.
AB  - CONTEXT: Family members of adults with mental illness often experience emotional
      distress and strained relationships. OBJECTIVE: To test the effectiveness of a
      family-led educational intervention, the Journey of Hope, in improving
      participants' psychological well-being and relationships with their ill
      relatives. DESIGN AND SETTING: A randomized controlled trial using a waiting list
      design was conducted in the community in 3 southeastern Louisiana cities.
      PARTICIPANTS: A total of 462 family members of adults with mental illness
      participated in the study, with 231 randomly assigned to immediate receipt of the
      Journey of Hope course and 231 assigned to a 9-month course waiting list.
      Intervention The Journey of Hope intervention consisted of 8 modules of education
      on the etiology and treatment of mental illness, problem-solving and
      communication skills training, and family support. MAIN OUTCOME MEASURES:
      Participants' psychological well-being and relationships with their ill relatives
      were assessed at study enrollment, 3 months after enrollment (at course
      termination), and 8 months after enrollment (6 months after course termination).
      Mixed-effects random regression analysis was used to predict the likelihood of
      decreased depressive symptoms, increased vitality, and overall mental health, and
      improved relationship ratings. RESULTS: Intervention group participants reported
      fewer depressive symptoms, greater emotional role functioning and vitality, and
      fewer negative views of their relationships with their ill relatives compared
      with control group participants. These improved outcomes were maintained over
      time and were significant (P<.05 for all) even when controlling for participant
      demographic and relative clinical characteristics. CONCLUSION: Results show that
      family-led educational interventions are effective in improving participants'
      psychological well-being and views of their relationships with ill relatives.

PMID- 16953008
TI  - Heart rate variability and depression.

PMID- 16953009
TI  - Long-term effects of universal preventive interventions on methamphetamine use
      among adolescents.
AB  - OBJECTIVE: To examine the long-term effects of universal preventive interventions
      on methamphetamine use by adolescents in the general population during their late
      high school years. DESIGN: Two randomized, controlled prevention trials. SETTING:
      Public schools in the Midwest from 1993 to 2004. PARTICIPANTS: Study 1 began with
      667 sixth grade students from 33 rural public schools; the follow-up included 457
      students. Study 2 began with 679 seventh grade students from 36 rural public
      schools; the follow-up assessment included 597 students. INTERVENTIONS: In study
      1, schools were assigned to the Iowa Strengthening Families Program (ISFP),
      Preparing for the Drug Free Years, or a control condition. In study 2, schools
      were assigned to a revised ISFP (SFP 10-14) plus Life Skills Training (SPF 10-14
      + LST), LST alone, or a control condition. RESULTS: Self-reports of lifetime and
      past-year methamphetamine use were collected at 6(1/2) years past baseline (study
      1) and at 4(1/2) and 5(1/2) years past baseline (study 2). In study 1, the ISFP
      past-year rate was 0.0% compared with 3.2% in the control condition (P = .04). In
      study 2, SFP 10-14 + LST showed significant effects on lifetime and past-year use
      at the 4(1/2) year follow-up (eg, 0.5% lifetime use in the intervention condition
      vs 5.2% in the control condition, P = .006); both SFP 10-14 + LST and LST alone
      had significant lifetime use effects at the 5(1/2) year follow-up. CONCLUSION:
      Brief universal interventions have potential for public health impact by reducing
      methamphetamine use among adolescents.

PMID- 16953010
TI  - Televised movie trailers: undermining restrictions on advertising tobacco to
      youth.
AB  - OBJECTIVE: To determine the proportion of televised movie trailers that included
      images of tobacco use during 1 year and the extent of youth exposure to those
      trailers. DESIGN: Content analysis combined with Nielsen data measuring media
      exposure. All movie trailers (N = 216) shown on television from August 1, 2001,
      through July 31, 2002. MAIN OUTCOME MEASURES: Exposure among youth aged 12 to 17
      years to televised movie trailers that included smoking imagery. RESULTS: Of the
      movie trailers televised during the study period, 14.4% (31 trailers) included
      images of tobacco use. Tobacco use was shown in 24.0% of the 23 trailers for R
      rated (restricted) movies and 7.5% of the 8 trailers for PG-13- and PG-rated
      (parental guidance) movies. Ninety-five percent of all youth aged 12 to 17 years
      in the United States saw at least 1 movie trailer depicting tobacco use on
      television during this 1 year, and 88.8% saw at least 1 of these trailers 3 or
      more times. CONCLUSIONS: Nearly all US youth aged 12 to 17 years were exposed to
      images of tobacco use on television in the context of a movie trailer during the
      study period. Given the relationship between youth exposure to tobacco use in
      movies and smoking initiation, the public health community should work to enact
      policy to reduce or eliminate the influence of tobacco use in televised movie
      trailers.

PMID- 16953011
TI  - Effect of open access scheduling on missed appointments, immunizations, and
      continuity of care for infant well-child care visits.
AB  - OBJECTIVE: To examine the effect of open access scheduling (OA) on infant well
      child care (WCC). DESIGN: Cluster randomization of 2 methods of OA compared with
      a baseline group (prior to OA). SETTING: Community health center pediatric
      clinic, August 1, 2003, to January 31, 2004. PARTICIPANTS: Ten providers
      (pediatricians and physician assistants) and 878 infants; 2-, 4-, and 6-month WCC
      visits were scheduled. INTERVENTIONS: Two scheduling methods were compared under
      the OA model: the OA future visit group scheduled their infant's next WCC visit
      when leaving the visit, and the OA same day group called for a same-day
      appointment. MAIN OUTCOME MEASURES: Missed appointment rates, on-time
      immunization rates, and continuity of care. RESULTS: Missed appointment rates
      decreased from 21% in the baseline group to 14% and 9% in the OA future visit and
      OA same day groups, respectively (P<.02). For 630 infants older than 5 months at
      study end, on-time immunization rates were 59% in the baseline group and 74% in
      both OA groups (P<.006). Of 412 infants with 2 or more WCC visits, 75% in the OA
      future visit group and 60% in the OA same day group saw the same provider for all
      visits (P = .001). This difference was due to differences among providers, not to
      the different scheduling methods. CONCLUSION: Open access scheduling decreases
      missed appointments for infant WCC visits and appears to increase on-time
      immunizations.

PMID- 16953012
TI  - Total body weight and waist circumference associated with chronic periodontitis
      among adolescents in the United States.
AB  - OBJECTIVE: To investigate whether measures of obesity are associated with
      periodontitis. DESIGN: A case-control study. SETTING: A nationally representative
      sample using data from the Third National Health and Nutrition Examination
      Survey. PARTICIPANTS: The sample included 2452 nonsmokers, aged 13 to 21 years,
      who received a periodontal examination and had complete information for age, sex,
      and smoking habits. MAIN EXPOSURES: Skinfold thickness, weight, and waist
      circumference were examined as independent variables in logistic regression
      models. Final models were adjusted for sex, race/ethnicity, poverty index ratio,
      last dental visit, and self-reported calcium intake. MAIN OUTCOME MEASURES: Cases
      were subjects with the presence of 1 or more periodontal sites with both a loss
      of tissue attachment of 3 mm and a probing depth of 3 mm (n = 111). Subjects who
      did not meet these criteria were classified as controls (n = 2341). RESULTS:
      Total body weight and waist circumference were associated with periodontitis, but
      the association varied by age. Adolescents aged 13 to 16 years were not at
      increased risk of chronic periodontitis, while adolescents aged 17 to 21 years
      had an increased risk per 1-kg increase in body weight (adjusted odds ratio, 1.06
      [95% confidence interval, 1.01-1.09]). Similarly, adolescents aged 13 to 16 years
      were not at increased risk for periodontal disease, while adolescents aged 17 to
      21 years were at an increased risk of periodontal disease per 1-cm increase in
      waist circumference (adjusted odds ratio, 1.05 [95% confidence interval, 1.01
      1.08]). CONCLUSION: Periodontitis may follow patterns similar to other chronic
      conditions that originate early in life and are related to central adiposity.

PMID- 16953013
TI  - Nutrition and exercise environment available to outpatients, visitors, and staff
      in Children's hospitals in Canada and the United States.
AB  - BACKGROUND: Children's hospitals should advocate for children's health by
      modeling optimum health environments. OBJECTIVES: To determine whether children's
      hospitals provide optimum health environments and to identify associated factors.
      DESIGN: Telephone survey. SETTING: Canadian and US hospitals with accredited
      pediatric residency programs. PARTICIPANTS: Food services directors or
      administrative dietitians. MAIN OUTCOME MEASURES: Health environment grades as
      determined for 4 domains quantifying (1) the amount of less nutritious food sold
      at cafeterias (cafeteria grade), (2) the presence of fast food outlets (outlet
      grade), (3) the amount of nutritious food alternatives available (healthful
      alternative grade), and (4) the presence of patient obesity or employee exercise
      programs (program grade). RESULTS: The overall response rate was 87%. Compared
      with Canadian hospitals, US hospitals had more food outlets (89% vs 50%) and more
      snack/beverage vending machines (median, 16 vs 12) (P = .001 for both), despite
      equivalent consumer numbers. External companies managed more outlets at US vs
      Canadian hospitals (65% vs 14%; P = .01), and, generally, US hospitals
      recuperated more revenue from their outlets. Worst cafeteria grade was associated
      with US hospital location (odds ratio [OR], 8.9; 95% confidence interval [CI],
      1.6-50; P = .01) and lower healthful alternative grade (OR, 0.016; 95% CI, 0.002
      0.15; P<.001). Lower grade in any domain was related to whether hospitals
      received more revenue from noncafeteria food outlets (OR, 1.7; 95% CI, 1.06-2.72;
      P = .03) and the presence of more internally operated cafeterias (OR, 2.3 per
      cafeteria; 95% CI, 1.53-3.36; P<.001). CONCLUSIONS: Children's hospitals provide
      suboptimal health environments. Reliance on revenue may be an important
      motivating factor encouraging the adoption of outlets that serve less nutritious
      food.

PMID- 16953014
TI  - Measuring effectiveness of dietetic interventions in child obesity: a systematic
      review of randomized trials.
AB  - OBJECTIVES: To assess the effectiveness of dietetic treatment for obese children
      and to report details of dietary interventions. DATA SOURCES: English-language
      articles from 1975 to 2003 available from health and medical databases. STUDY
      SELECTION: Randomized controlled trials with subjects younger than 18 years of
      age that included a dietary intervention in isolation or in combination with
      lifestyle modifications and/or psychological therapies. One person searched the
      databases; 2 people independently critically appraised the articles for
      methodological quality and then extracted data using standardized tools. DATA
      EXTRACTION: Thirty-seven randomized controlled trials met the inclusion criteria;
      17 contained sufficient information for a Forest plot of the standardized
      effects. Eight studies had a true control and were included in a meta-analysis.
      The random effects model was reported if the Q noncombinability chi(2) statistic
      was significant at the 10% level because it has low power as a strict test of
      homogeneity. DATA SYNTHESIS: The 2 strongly qualified meta-analyses suggest that
      interventions that include a dietary treatment do achieve relative weight loss.
      Details of the dietary intervention or participant food intake are rarely
      described. CONCLUSIONS: It is not possible to evaluate the effectiveness of
      dietary treatment for childhood obesity because of the lack of high-quality
      studies and the heterogeneity of designs, treatment combinations, outcome
      measures, and follow-up. There is an urgent need to improve the quality of
      studies in this area because childhood obesity poses major health risks for
      populations, yet there is limited evidence on which to base treatment strategies.

PMID- 16953015
TI  - Hispanic concentration and the conditional influence of collective efficacy on
      adolescent childbearing.
AB  - OBJECTIVE: To determine how Hispanic residential concentration moderates the
      relationship between neighborhood collective efficacy and teenage birth rates.
      DESIGN: Cross-sectional analysis of census tract level survey data and birth
      records. SETTING: Sixty-five Los Angeles (California) County census tracts in
      2000 and 2001. PARTICIPANTS: Measures of neighborhood collective efficacy from
      2600 adults from the Los Angeles Family and Neighborhood Study (LAFANS) survey
      were linked with demographic information from the US 2000 Census and Los Angeles
      County birth records for 10- through 19-year-old mothers. MAIN EXPOSURES:
      Collective efficacy and Hispanic residential concentration. MAIN OUTCOME
      MEASURES: Married and unmarried teenage birth rates. RESULTS: In census tracts
      with less than a 50% Hispanic population, a 1-SD increase in collective efficacy
      was associated with a 5.07 births per 1000 decrease in the unmarried teenage
      birth rate (P<.05). In census tracts with a 50% or greater Hispanic population, a
      1-SD increase in collective efficacy was not statistically related to unmarried
      rates, but it was associated with a 3.43 increase in the married teenage birth
      rate (P<.05). CONCLUSIONS: Collective efficacy may help reduce adolescent
      childbearing in some, but not all, neighborhoods. An interaction between
      collective efficacy and Hispanic population concentration suggests cultural
      variation may play a role in how collective efficacy influences adolescent
      fertility. Possible explanations for the positive relationship between collective
      efficacy and married birth rates found in segregated Hispanic neighborhoods
      include profertility orientations and availability of childrearing networks for
      young parents. To help harness social capital to improve public health outcome,
      we suggest future studies examine the role of community cultural variation.

PMID- 16953016
TI  - Obese children and adolescents: a risk group for low vitamin B12 concentration.
AB  - OBJECTIVE: To assess whether overweight children and adolescents are at an
      increased risk for vitamin B(12) deficiency. DESIGN: Prospective descriptive
      study. SETTING: Two pediatric endocrine centers in Israel. PARTICIPANTS: Three
      hundred ninety-two children and adolescents were divided into 2 groups as
      follows: the normal-weight group had body mass indexes, calculated as weight in
      kilograms divided by height in meters squared, under the 95th percentile (<1.645
      standard deviation scores; n = 228); the obese group had body mass indexes equal
      to or above the 95th percentile (>/=1.645 standard deviation scores; n = 164).
      INTERVENTION: We measured vitamin B(12) concentrations. Low serum B(12) was
      defined as a B(12) concentration less than 246 pg/mL, and vitamin B(12)
      deficiency was defined as a concentration below 211 pg/mL. MAIN OUTCOME MEASURE:
      Vitamin B(12) concentrations corrected for body mass index standard deviation
      scores, age, and sex. RESULTS: Median concentration of serum B(12) in normal-
      weight children was 530 pg/mL and in obese children, 400 pg/mL (P<.001). Low
      B(12) concentrations were noted in 10.4% of the obese children compared with only
      2.2% of the normal weight group (P<.001). Vitamin B(12) deficiency was noted in
      12 children, 8 (4.9%) of the obese subjects and 4 (1.8%) of the normal weight
      group (P = .08). After we adjusted for age and sex, obesity was associated with a
      4.3-fold risk for low serum B(12), and each unit increase in body mass index
      standard deviation score resulted in an increased risk of 1.24 (95% confidence
      interval, 0.99-1.56). CONCLUSIONS: Obesity in children and adolescents was
      associated with an increased risk of low vitamin B(12) concentration. We
      recommend that dietary assessment of obese children should include an estimation
      of vitamin B(12) intake. The possibility of vitamin B(12) deficiency in addition
      to other micronutrient deficiencies should be considered in obese children.

PMID- 16953017
TI  - Human herpesvirus 8 infection among adolescents in the REACH cohort.
AB  - OBJECTIVE: Human herpesvirus 8 (HHV-8) infection is common among children in
      areas where Kaposi sarcoma is endemic. Human herpesvirus 8 is uncommon in
      children but prevalent in adults at risk for human immunodeficiency virus (HIV)
      infection in the United States, including men who have sex with men (MSM) and
      women who engage in high-risk sexual behavior. We examined the prevalence and
      predictors of HHV-8 infection among adolescents with or at high risk for
      acquiring HIV infection. DESIGN: Cross-sectional analysis. SETTING: National
      study of HIV infection among adolescents in primary care. PARTICIPANTS: A total
      of 537 young adults practicing high-risk sexual behavior, of which 403 were women
      and 134 were men; among the 134 men, 75% were MSM. INTERVENTIONS: Detailed
      questionnaires and testing for serum antibodies to HHV-8. OUTCOME MEASURE:
      Detection of serum antibodies to HHV-8. RESULTS: Sixty (11.2%) of 537 young
      adults were HHV-8 seropositive, including 20 MSM (19.6%), 2 male heterosexuals
      (6.5%), and 27 female heterosexuals (8.2%). The prevalence of HHV-8 in HIV
      positive MSM (17/74 [23.0%]) was twice as high as that in HIV-negative MSM (3/28
      [10.7%]) (P = .18), but no characteristic predicted HHV-8 infection among MSM. In
      multivariate analysis, history of gonorrhea (odds ratio [OR], 2.8; 95% confidence
      interval [CI], 1.4-5.7; P<.01), history of having sex with women (OR, 2.4; 95%
      CI, 1.1-5.3; P = .03), and African American race (OR, 3.4; 95% CI, 1.1-10.0; P =
      .03) were associated with HHV-8 infection among women. CONCLUSIONS: Human
      herpesvirus 8 is common among US adolescents practicing high-risk sexual
      behaviors. Sexual identity, race, and sexual behavior may influence the risk of
      infection with HHV-8 in women.

PMID- 16953018
TI  - Ruling out the need for antibiotics: are we sending the right message?
AB  - OBJECTIVES: To examine the relationships among physician-parent communication
      practices, physicians' perceptions of parental expectations for antibiotic
      treatment, and inappropriate antibiotic prescribing for viral upper respiratory
      tract infections. DESIGN: Cross-sectional study of pediatric encounters motivated
      by cold symptoms between October 1, 2000, and June 30, 2001. Each encounter was
      videotaped. Physicians completed a postvisit survey that measured whether they
      perceived the parent as expecting antibiotics. Coded communication variables were
      merged with survey variables. Multivariate analyses identified key predictors of
      parent-physician communication practices, physician perceptions of parents'
      expectations for antibiotics, and inappropriate antibiotic prescribing for viral
      conditions. SETTING: Twenty-seven pediatric practices in Los Angeles, Calif.
      PARTICIPANTS: Thirty-eight pediatricians and 522 consecutively approached parents
      of children with cold symptoms. MAIN OUTCOME MEASURES: Physicians' perceptions of
      parental expectations for antibiotics, inappropriate antibiotic prescribing, and
      parental questioning of nonantibiotic treatments. RESULTS: Physicians were 20.2%
      more likely to perceive parents as expecting antibiotics when they questioned the
      physician's treatment plan (P = .004; 95% confidence interval, 6.3%-34.0%). When
      physicians perceived parents as expecting antibiotics, they were 31.7% more
      likely to inappropriately prescribe them (P<.001; 95% confidence interval, 16.0%
      47.3%). Parents were 24.0% more likely to question the treatment plan when the
      physician ruled out the need for antibiotics (P = .004; 95% confidence interval,
      7.7%-40.3%). CONCLUSIONS: Parental questioning of the treatment plan increases
      physicians' perceptions that antibiotics are expected and thus increases
      inappropriate antibiotic prescribing. Treatment plans that focus on what can be
      done to make a child feel better, rather than on what is not needed, ie,
      antibiotics, may decrease inappropriate antibiotic prescribing.

PMID- 16953019
TI  - Randomized controlled trial of a prenatal and postnatal lactation consultant
      intervention on infant health care use.
AB  - OBJECTIVE: To determine whether infants of women randomized to a prenatal and
      postpartum lactation support intervention incur fewer otitis media-, respiratory
      tract-, or gastrointestinal-related visits than controls. DESIGN: Randomized,
      unmasked controlled trial recruiting women from prenatal care settings.
      Breastfeeding sensitive (BFS) illness visits for otitis media or respiratory
      tract or gastrointestinal complaints were obtained up to 12 months. SETTING: Two
      urban community health centers. PARTICIPANTS: Analytic sample of 338 low-income,
      primarily Hispanic and/or black mother-infant dyads (n = 163 for the intervention
      group and n = 175 for the control group). INTERVENTION: Study lactation
      consultants attempted 2 prenatal meetings, 1 postpartum hospital and/or home
      visit, and telephone calls as needed. Controls received the standard of care.
      MAIN OUTCOME MEASURES: Combined outpatient and emergency department visits with
      illness and BFS illness diagnoses. RESULTS: There was a significant interaction
      between treatment and Medicaid; among those not receiving Medicaid, the number of
      otitis media visits was higher among controls (P</=.03). Visits for any illness
      and BFS, gastrointestinal, or respiratory tract illnesses did not differ by
      treatment group. Intervention group infants received more breast milk than
      controls, but exclusive breastfeeding rates remained low and did not differ
      between groups at any point. CONCLUSIONS: Only the number of otitis media visits
      was reduced, in a subset of the intervention group. The intervention did not
      reduce visits for respiratory tract or gastrointestinal illness. Limited
      intervention contact and low exclusive breastfeeding rates may have attenuated
      intervention effects. Future interventions designed to yield markedly increased
      breastfeeding rates may show greater effects in low-income multiethnic samples.
      Health coverage for visits may moderate intervention effects.

PMID- 16953020
TI  - Relationship between the decision to take a child to the clinic for abdominal
      pain and maternal psychological distress.
AB  - BACKGROUND: Among adults with functional gastrointestinal disorders,
      psychological distress influences who consults a physician, but little is known
      about predictors of consultation when the patient is a child. OBJECTIVE: To
      determine the relative contributions of psychological symptoms of the mother,
      psychological symptoms of the child, severity of child abdominal pain, and family
      stress to consultation. DESIGN: Observational study. SETTING: Health maintenance
      organization. PARTICIPANTS: Two hundred seventy-five mothers of 334 children who
      had abdominal pain in the past 2 weeks, as per child self-report. MAIN OUTCOME
      MEASURES: Mothers completed questionnaires about themselves (Symptom Checklist 90
      Revised) and their children (school absences, medication use, and the Child
      Behavior Checklist). Children completed the Pain Beliefs Questionnaire to assess
      perceived pain severity. RESULTS: Thirty-nine children had been taken to the
      clinic for abdominal pain symptoms at least once in the past 3 months
      (consulters), whereas 295 were nonconsulters. Logistic regression analyses
      revealed that both the child's self-report of perceived pain severity (P<.001)
      and maternal psychological symptoms (P = .006) predicted consultation. Although
      children who visited physicians had significantly more psychological symptoms,
      this was not a significant predictor of consultation after adjusting for maternal
      psychological symptoms. Family stress did not predict consultation. CONCLUSION:
      The decision to take a child to the clinic for abdominal pain is best predicted
      by maternal psychological distress and the child's perceived pain severity.

PMID- 16953021
TI  - Effect of missed opportunities on influenza vaccination rates among children with
      asthma.
AB  - OBJECTIVES: To assess rates of influenza vaccination among children with asthma;
      document the frequency, timing, and patterns of missed opportunities to vaccinate
      during successive influenza seasons; and project potential influenza vaccination
      rates that could be achieved by reducing or eliminating missed opportunities.
      SETTING: Michigan Medicaid program during the 2001-2002 and 2002-2003 influenza
      seasons. DESIGN: Retrospective cohort analysis of administrative claims.
      PARTICIPANTS: We evaluated the claims of 4358 children aged 5 to 18 years with
      persistent asthma who were continuously enrolled in Medicaid. MAIN OUTCOME
      MEASURES: Influenza vaccinations and missed opportunities assessed using
      procedure and diagnosis codes. RESULTS: During the 2001-2002 season, 16.7% of
      children with asthma received an influenza vaccination; during 2002-2003, 21.8%
      received the vaccine (9.5% vaccinated in both seasons). However, 76.5% of
      children had at least 1 office visit during the 2001-2002 influenza season (75.3%
      during 2002-2003). Among children without influenza vaccination, 72.9% had at
      least 1 missed opportunity for vaccination during the 2001-2002 season and 69.3%
      during 2002-2003. The most common outcome was having at least 1 missed
      opportunity (39.6%) in each of 2 successive influenza seasons. Eliminating missed
      opportunities prior to the historical peak of influenza season would have
      increased the influenza vaccination rate among this population of children to
      76%. CONCLUSIONS: Missed opportunities for influenza vaccination among children
      with asthma are common and are often repeated from one influenza season to the
      next. Future studies should assess how interventions could be aimed at patients
      and health care professionals to improve awareness of the need for annual
      influenza vaccination.

PMID- 16953022
TI  - Children treated at an expeditionary military hospital in Iraq.
AB  - OBJECTIVE: To describe the treatment of children at an expeditionary military
      hospital in wartime Iraq. DESIGN: Descriptive, retrospective study. SETTING: The
      332nd Air Force Theater Hospital in Balad, Iraq, January 1, 2004, to May 31,
      2005. PATIENTS: All 85 children (of 1626 total patients) evaluated and treated at
      the hospital during the study period. INTERVENTIONS: Indicated surgical
      procedures performed on children. MAIN OUTCOME MEASURES: Age, sex, diagnosis,
      injury, operations, and complications for children during the study period.
      RESULTS: The 85 children (age range, 1 day to 17 years; mean, 8 years)
      represented 5.2% of all patients. Thirty-four (61%) of the 56 children for whom
      sex was recorded were male. Injury was the diagnosis for 48 children (56%). Of
      these, the cause was fragmentation wound in 25 children (52%), penetrating trauma
      in 11 (23%), burn in 9 (19%), and blunt trauma in 3 (6%). The site of injury was
      the lower extremity in 18 children (38%), head in 11 (23%), upper extremity in 8
      (17%), abdomen in 8 (17%), and chest in 3 (6%). Nontraumatic conditions had
      congenital, infectious, gastrointestinal, and neoplastic causes. During the
      study, 134 operations were performed on 63 children. There were 5 deaths.
      CONCLUSIONS: Expeditionary military hospitals will encounter both injured and
      noninjured children seeking medical care. To optimize the care of these children,
      it will be necessary to provide the proper personnel, training, and equipment.

PMID- 16953023
TI  - Fetal origin of childhood disease: intrauterine growth restriction in term
      infants and risk for hypertension at 6 years of age.
AB  - OBJECTIVE: To examine the association between intrauterine growth restriction
      (IUGR) status at birth among full-term infants, exposure to substance use during
      pregnancy, and risk of hypertension at 6 years of age. DESIGN: Prospective
      evaluation of high-risk children. SETTING: Four centers of the National Institute
      of Child Health and Human Development Neonatal Research Network. PARTICIPANTS:
      One thousand three hundred eighty-eight infants (600 cocaine exposed, 781
      nonexposed, and 7 indeterminate, matched by gestational age, race, and sex), were
      enrolled at these sites. Nine hundred fifty children (415 exposed, 535
      nonexposed) were followed up for 6 years. Intervention Right arm blood pressure
      was measured using the Dinamap portable adult/pediatric monitor with appropriate
      cuff size. Main Outcome Measure Blood pressure levels. Hypertension was defined
      as either systolic or diastolic blood pressure higher than the 95th percentile
      for sex, age, and height. RESULTS: Eight hundred ninety-one children had blood
      pressure data at 6 years of age: 516 were born at full term; 144 (28%) of the 516
      children had a diagnosis of IUGR at birth. At 6 years of age, 93 (19%) of 516
      children had hypertension. Of 144 children with IUGR, 35 (24%) had hypertension
      as compared with 58 (16%) of 372 children without IUGR (P<.05). Twenty percent of
      cocaine-exposed children had hypertension as compared with 16% of nonexposed
      children (P = .20). Intrauterine growth restriction status at birth was
      significantly associated with hypertension (relative risk, 1.8 [95% confidence
      interval, 1.2-2.7]) when multivariable Poisson regression analysis was performed
      adjusting for site; maternal race, education, and tobacco, marijuana, alcohol,
      and cocaine use during pregnancy; and child's current body mass index (calculated
      as weight in kilograms divided by height in meters squared). CONCLUSION: In term
      infants, IUGR is linked to risk of hypertension in early childhood, which may be
      a marker for adult cardiovascular disease.

PMID- 16953024
TI  - Picture of the month. Nutritional rickets.

PMID- 16953025
TI  - Denial of insurance authorization at a subspecialty office as a cause of missed
      opportunities for influenza vaccination in children with asthma.

PMID- 16953026
TI  - Internet cigarette vendors' lack of compliance with a California state law
      designed to prevent tobacco sales to minors.

PMID- 16953027
TI  - Correlation between CD4 count and intensity of Candida colonization in the
      oropharynx of HIV-infected/ AIDS patient.
AB  - AIM: To know the correlation between CD4 count and intensity of Candida
      colonizations in the oropharynx of HIV-infected/AIDS patients, to get the
      prevalence of oropharyngeal candidiasis (OPC), and to know what kind of Candida
      species that causes oropharynx candidiasis of HIV-infected/AIDS patients.
      METHODS: A cross-sectional study was conducted in HIV-infected/AIDS patients who
      came as outpatients and inpatients in Cipto Mangunkusumo Hospital. The patients
      were interviewed, physically examined, their CD4 counts were checked, and their
      mouth rinse samples were taken to be cultured. Candida species was identified in
      CHROMagar media, and data were processed. RESULTS: From September 2004 until
      January 2005, 60 HIV-infected/AIDS patients were included in this study. There
      were 86.7% males and 13.3% females. Majority of the patients were from 20-30
      years age group (85%). The most frequent transmission was among drug users (75%)
      followed by sexual contact (18.3%). The median of CD4 counts was 100 cells/il,
      ranged from 2 to 842 cells/il. Proportion of the OPC was 63.3% (CI 95% = 51.1 -
      75.5). From 59 Candida isolates in this study, 74.58% were C. albicans. Candida
      non C. albicans species that were found in this trial were C. krusei, C.
      parapsilosis and C. tropicalis. There was significant correlation between low CD4
      counts and high intensity of Candida colonization on the oropharynx of the
      subjects (r = -0.756). CONCLUSION: There was strong negative correlation (r = 
      0.756) between CD4 count and intensity of Candida colonization in the oropharynx
      of HIV-infected/AIDS patients. Proportion of OPC in this study was 63.3%. The
      most frequent species found in the oropharynx of the subjects was C. albicans.

PMID- 16953028
TI  - Fibrinogen and plasminogen activator inhibitor-1 level in peripheral arterial
      disease of type 2 diabetes patients.
AB  - AIM: To determine association of fibrinogen and plasminogen activator inhibitor-1
      with peripheral arterial disease (PAD) in type 2 diabetes patients. METHODS: This
      is a cross-sectional study with 52 type 2 diabetes patients of 41-74 years old.
      The subjects were divided into two groups, those who were diagnosed with PAD (16)
      and without PAD (36). Diagnosis of PAD was based on the ankle brachial index
      (ABI) measurement. Fibrinogen and plasminogen activator inhibitor-1 (PAI-1) level
      were evaluated as hemostatic factors. The two groups were compared for age, sex,
      smoking, plasma fasting glucose, total cholesterol, low density lipoprotein
      (LDL), high density lipoprotein (HDL), triglyceride concentrations, diabetes
      duration, systolic blood pressure and diastolic blood pressure level. Statistical
      analyse were conducted to check the significance of differences between variables
      in the two groups as well as interrelationship between hemostatic factors and
      other parameters. RESULTS: Fibrinogen was similar in both group (402.42 +/- 74.44
      mg/dl in PAD group and 322.45 +/- 101.05 mg/dl in non-PAD group) (p= 0.259). PAI
      1 was also similar in both group (8.93 +/- 11.02 IU/ml in PAD group and 7.06 +/-
      7.32 IU/ml in non-PAD group) (p=0.721). Hyperfibrinogenemia was more prevalent in
      PAD group (68.8%) than in non-PAD group (25%) (p= 0.005). CONCLUSION: Our data
      showed that fibrinogen and PAI-1 level were similar in both groups. As a risk
      factor hyperfibrinogenemia was more prevalent in PAD group.

PMID- 16953029
TI  - Evaluation of four-years hospital implementation of DOTS strategy (1998 - 2002).
AB  - AIM: To obtain an overview of the problem and to know the success and result of
      DOTS method in tuberculosis treatment. METHODS: Application of DOTS at the
      hospital was done every Monday during working hours at the outpatient clinic
      pulmonology clinic Department of Internal Medicine of Dr. Mohammad Hoesin
      Hospital in Palembang, Indonesia. Selection of patients was done at the general
      outpatient clinic. Patients suspected with pulmonary TB were clinically
      investigated with the sputum Acid Fast Bacilli 3x test (spot, morning, spot). If
      the sputum tests were negative, the patients underwent Chest X Ray. Patients with
      complete data were referred to the DOTS clinic. Hospital nurses and doctor
      residents from internal medicine filled up the medical records, TB form and
      registration of identity card, determined the Observer of Medicine Consumption
      (PMO) and provided the "Informed Consent". Education and motivation on the
      problem of tuberculosis were conducted by doctors and nurses. Finally, patients
      are requested to consume medicine by their observer with assistance from the
      pharmacist, and were given DOTS medicine for 1 - 2 weeks. RESULTS: At the end of
      August 2002, 517 patients had completed treatment. The cure rate from positive
      sputum AFB was 82.17% (295 from 359 patients); 87.7% for category I (221 from 252
      patients) and 69.2% for category II (74 from 107 patients). This can be increased
      to 85.3.% (295/344; Total), 92.5% (221/239 ; category I) and 70.5% (74/105;
      category II), those patients transfered out were not included in the
      denomination. The percentage of those who completed category III treatment was
      91.8% (145 from 158 patients), with a drop - out/default rate of 6.2%.
      CONCLUSION: DOTS strategy in hospital was done by DOTS team consisted of doctors,
      nurses, assistant pharmacist and health workers. The number of TB cases in Moh.
      Hoesin Hospital Palembang in category I is more than category II/III, RK Charitas
      Category III is more than category I/II which are unemployed, primary school and
      productive ages. DOTS treatment on 2006 was done by FDC (Fixed Dose Combination).

PMID- 16953031
TI  - The Petai China study: metabolic syndrome among obese Indonesian Chinese
      adolescents (preliminary report).
AB  - AIM: We examined 251 boys and 259 young girls of chinese offspring, age of 12 to
      18 years old from 5 schools around North Jakarta and West of Jakarta. The
      variables observed are Body Mass Index, waist circumference, fasting sugar level,
      fasting HDL-cholesterol, tryglyceride and insulin level (fasting). METHODS: Cross
      sectional epidemiology survey. RESULTS: We found 125 youngsters as obese which
      are 82 young boys and 43 young girls. 47 of the 510 students observed
      anthropometrically agreed to continue the examination for blood test. The
      prevalence of the obesity is 4,9% of the population observed and the prevalence
      of the metabolic syndrome found higher among male students (19,14%) of 10,63%
      among female students. For the obese population, the criterion of metabolic
      syndrome is found higher (35,71%). CONCLUSION: We determined the existence of
      metabolic syndrome among the youth in Jakarta that the prevalence of the
      metabolic syndrome is higher among the obese population.

PMID- 16953030
TI  - Correlation between left ventricular mass and visceral fat thickness in obese
      women.
AB  - AIM: This study was aimed to measure left ventricular mass, which partly
      determines the function of the left ventricle, in obese women. METHODS: The total
      number of study subjects was 90, which consisted of 45 obese women (BMI >or= 25
      Kg/m2) and 45 non-obese women (BMI < 25 Kg/m2) as control group. They were
      evaluated by M mode echocardiography and abdominal CT to measure visceral fat,
      blood pressure, insulin resistance and waist circumference. Correlation was
      assessed for both groups. RESULTS: There were significant differences in the left
      ventricular mass of the obese and non-obese group (P= 0.000), systolic blood
      pressure (P = 0.000), diastolic blood pressure (P = 0.006), waist circumference
      (P = 0.000), visceral fat (P = 0.000), and HOMA-IR (P = 0.000). With bivariant
      analysis, it is concluded that there are significant correlations between left
      ventricular mass and visceral fat (r = 0.67, P = 0.000); between BMI and left
      ventricular mass (r = 0.67, P = 0.000); between waist circumference and left
      ventricular mass (r = 0.72, P = 0.000); and also between HOMA-IR and left
      ventricular mass (r = 0.57, P = 0.000). CONCLUSION: There are significant
      correlations between increased left ventricular mass and visceral fat, BMI, waist
      circumference and HOMA-IR among Indonesian women. So far, this study has shown a
      correlation between obesity and high cardiovascular risk.

PMID- 16953032
TI  - Drug provocation test in patient with antituberculosis drug allergy.
AB  - Hypersensitivity reaction is an unexpected drug adverse effect which sometimes
      can lead to fatal condition. Confirmation of the suspected drugs that cause
      hypersensitivity reaction is sometimes difficult. Drug provocation test is still
      a gold standard to establish the diagnosis of hypersensitivity to certain drugs
      or agents. Drug provocation test is a controlled drug treatment which aims at
      making diagnosis of hypersensitivity reaction to drugs. We reported a
      demonstration case of a 47 year-old female patient with hypersensitivity to anti
      tuberculosis drugs (isoniazid, rifampicin, pyrazinamid and ethambutol). Drug
      provocation test is important in this case to confirm which drug had caused
      hypersensitivity reaction because anti tuberculosis drugs were the treatment of
      choice for her illness.

PMID- 16953033
TI  - Hepatocarcinogenesis in viral Hepatitis B infection: the role of HBx and p53.
AB  - Infection of Hepatitis B Virus (HBV) is a risk factor of chronic active hepatitis
      (CAH), hepatic cirrhosis and hepatocellular carcinoma (HCC). Infection of HBV may
      develop to HCC without antecedent hepatic cirrhosis. Pathogenesis of HBV causing
      malignant changes has not been fully understood. HBx, a protein of HBV, is an
      activator of transcription process involved in hepatocarcinogenesis. Most of
      human cancer associated with mutation of p53, a Tumor Suppressor Genes, a protein
      serves as cellular protection for growth and cell division, which is one of
      predisposition factor of hepatocarcinoma. Some studies indicate the correlation
      between mutation / inactivation of p53 and HBV protein x (HBx) in
      hepatocarcinogenesis. In that process, HBx will suppress p53 function, which will
      lead to ineffective liver cell division and resulting in HCC.

PMID- 16953034
TI  - Rectal hemangioma.

PMID- 16953035
TI  - Intraoperative radiation therapy using a mobile electron linear accelerator:
      field matching for large-field electron irradiation.
AB  - Intraoperative radiation therapy (IORT) consists of delivering a large, single
      fraction dose of radiation to a surgically exposed tumour or tumour bed at the
      time of surgery. With the availability of a mobile linear accelerator in the OR,
      IORT procedures have become more feasible for medical centres and more accessible
      to cancer patients. Often the area requiring irradiation is larger than what the
      treatment applicators will allow, and therefore, two or more adjoining fields are
      used. Unfortunately, the divergence and scattering of the electron beams may
      cause significant dose variations in the region of the field junction.
      Furthermore, because IORT treatments are delivered in a large single fraction,
      the effects of underdosing or overdosing could be more critical when compared to
      fractionated external beam therapy. Proper matching of the fields is therefore an
      important technical aspect of treatment delivery. We have studied the matching
      region using the largest flat applicator available for three different
      possibilities: abutting the fields, leaving a small gap or creating an overlap.
      Measurements were done using film dosimetry for the available energies of 4, 6, 9
      and 12 MeV. Our results show the presence of clinically significant cold spots
      for the low-energy beams when the fields are either gapped or abutted, suggesting
      that the fields should be overlapped. No fields should be gapped. The results
      suggest that an optimal dose distribution may be obtained by overlapping the
      fields at 4 and 6 MeV and simply abutting the fields at 9 and 12 MeV. However,
      due to uncertainties in the placement of lead shields during treatment delivery,
      one may wish to consider overlapping the higher energy fields as well.

PMID- 16953036
TI  - Multiplicative optical tomography of cardiac electrical activity.
AB  - Cardiac electrical activity can be mapped today through the response of voltage
      sensitive dyes; but poor transparency of muscle tissue has enforced shallow-depth
      imaging. We present a three-dimensional (3D) reconstruction method for electrical
      activity deep inside the myocardial wall. Our approach is nonlinear and differs
      substantially from standard diffusive optical tomography. It does not require
      matrix inversion, data regularization or a priori information concerning the
      original object. Opposite sides of a slab-shaped preparation are scanned in
      parallel by detection and illumination points with a constant vector offset
      between illumination and detection axes (biaxial scanning). Scanning is performed
      in two perpendicular directions. In each direction, a pair of 2D images is
      obtained under offsets of opposite signs. These two pairs are the input for a
      multiplicative reconstruction algorithm, whose output is a 3D image. The overall
      procedure was successfully tested on computer-generated sources that include
      points, lines and hemispheres, patterned after actual electrophysiological
      excitations. The algorithm is computationally efficient and stable with respect
      to varying noise levels in the raw data.

PMID- 16953037
TI  - Image segmentation of trabecular spongiosa by visual inspection of the gradient
      magnitude.
AB  - Recent advances in physical models of skeletal dosimetry utilize high-resolution
      3-dimensional microscopic computed tomography images of trabecular spongiosa.
      These images are coupled to radiation transport codes to assess energy deposition
      within active bone marrow and trabecular endosteum. These transport codes rely
      primarily on the segmentation of the spongiosa images into bone and marrow
      voxels. Image thresholding has been the segmentation of choice for bone sample
      images because of its extreme simplicity. However, the ability of the
      segmentation to reproduce the physical boundary between bone and marrow depends
      on the selection of the threshold value. Statistical models, as well as visual
      inspection of the image, have been employed extensively to determine the correct
      threshold. Both techniques are affected by partial volume effect and can provide
      unexpected results if performed without care. In this study, we propose a new
      technique to threshold trabecular spongiosa images based on visual inspection of
      the image gradient magnitude. We first show that the gradient magnitude of the
      image reaches a maximum along a surface that remains almost independent of
      partial volume effect and that is a good representation of the physical boundary
      between bone and marrow. A computer program was then developed to allow a user to
      compare the position of the iso-surface produced by a threshold with the gradient
      magnitude. The threshold that produces the iso-surface that best coincides with
      the maximum gradient is chosen. The technique was finally tested with a set of
      images of a true bone sample with different resolutions, as well as with three
      images of a cube of Duocell aluminium foam of known mass and density. Both tests
      demonstrate the ability of the gradient magnitude technique to retrieve sample
      volumes or media volume fractions with 1% accuracy at 30 microm voxel size.

PMID- 16953038
TI  - Real-time respiration monitoring using the radiotherapy treatment beam and four
      dimensional computed tomography (4DCT)--a conceptual study.
AB  - Real-time knowledge of intra-fraction motion, such as respiration, is essential
      for four-dimensional (4D) radiotherapy. Surrogate-based and internal-fiducial
      based methods may suffer from one or many drawbacks such as false correlation,
      being invasive, delivering extra patient radiation, and requiring complicated
      hardware and software development and implementation. In this paper we develop a
      simple non-surrogate, non-invasive method to monitor respiratory motion during
      radiotherapy treatments in real time. This method directly utilizes the treatment
      beam and thus imposes no additional radiation to the patient. The method requires
      a pre-treatment 4DCT and a real-time detector system. The method combines off
      line processes with on-line processes. The off-line processes include 4DCT
      imaging and pre-calculating detector signals at each phase of the 4DCT based on
      the planned fluence map and the detector response function. The on-line processes
      include measuring detector signal from the treatment beam, and correlating the
      measured detector signal with the pre-calculated signals. The respiration phase
      is determined as the position of peak correlation. We tested our method with
      extensive simulations based on a TomoTherapy machine and a 4DCT of a lung cancer
      patient. Three types of simulations were implemented to mimic the clinical
      situations. Each type of simulation used three different TomoTherapy delivery
      sinograms, each with 800 to 1000 projections, as input fluences. Three arbitrary
      breathing patterns were simulated and two dose levels, 2 Gy/fraction and 2
      cGy/fraction, were used for simulations to study the robustness of this method
      against detector quantum noise. The algorithm was used to determine the breathing
      phases and this result was compared with the simulated breathing patterns. For
      the 2 Gy/fraction simulations, the respiration phases were accurately determined
      within one phase error in real time for most projections of the treatment, except
      for a few projections at the start and end of the treatment in which beam
      intensities were extremely low. At 2 cGy/fraction dose level, the method can
      still determine the respiration phase very well with less than 10% of projections
      having more than two phases (approximately 1 s) error. This technique can also be
      applied in other delivery systems such as orthogonal x-ray systems, although in
      those cases it would entail the delivery of additional non-treatment radiation.

PMID- 16953039
TI  - Dual-energy mammography: simulation studies.
AB  - This paper presents a mammography simulator and demonstrates its applicability in
      feasibility studies in dual-energy (DE) subtraction mammography. This mammography
      simulator is an evolution of a previously presented x-ray imaging simulation
      system, which has been extended with new functionalities that are specific for DE
      simulations. The new features include incident exposure and dose calculations,
      the implementation of a DE subtraction algorithm as well as amendments to the
      detector and source modelling. The system was then verified by simulating
      experiments and comparing their results against published data. The simulator was
      used to carry out a feasibility study of the applicability of DE techniques in
      mammography, and more precisely to examine whether this modality could result in
      better visualization and detection of microcalcifications. Investigations were
      carried out using a 3D breast software phantom of average thickness,
      monoenergetic and polyenergetic beam spectra and various detector configurations.
      Dual-shot techniques were simulated. Results showed the advantage of using
      monoenergetic in comparison with polyenergetic beams. Optimization studies with
      monochromatic sources were carried out to obtain the optimal low and high
      incident energies, based on the assessment of the figure of merit of the
      simulated microcalcifications in the subtracted images. The results of the
      simulation study with the optimal energies demonstrated that the use of the DE
      technique can improve visualization and increase detectability, allowing
      identification of microcalcifications of sizes as small as 200 microm. The
      quantitative results are also verified by means of a visual inspection of the
      synthetic images.

PMID- 16953040
TI  - A strategy to minimize errors from differential intrafraction organ motion using
      a single configuration for a 'breathing' multileaf collimator.
AB  - Intensity-modulated radiation therapy (IMRT) can be delivered by the 'sliding
      leaves' dynamic multileaf collimator (DMLC) technique. Intrafraction organ motion
      can be accommodated by arranging an identical tracking motion for 'breathing
      leaves'. However, this is only possible for very specific circumstances such as
      regular, mathematically parameterizable, rigid-body, density-conserving, one
      dimensional translations. In this paper, we investigate what happens when planes
      of tissue in the line of sight of the MLC have differential motion with respect
      to the moving leaves. In this situation, there is no solution to the problem and
      a perfect tracking motion cannot be arranged. However, an iterative minimization
      of-errors 'solution' (or strategy) can be found and the technique is presented
      for this. From this, under certain mathematically simple differential motions it
      is possible to obtain some elegant algebraic solutions which are presented. In
      general, however, a lengthy computational minimization is required and results of
      examples of these are presented.

PMID- 16953041
TI  - Three-dimensional focus of attention for iterative cone-beam micro-CT
      reconstruction.
AB  - Three-dimensional iterative reconstruction of high-resolution, circular orbit
      cone-beam x-ray CT data is often considered impractical due to the demand for
      vast amounts of computer cycles and associated memory. In this paper, we show
      that the computational burden can be reduced by limiting the reconstruction to a
      small, well-defined portion of the image volume. We first discuss using the
      support region defined by the set of voxels covered by all of the projection
      views. We then present a data-driven preprocessing technique called focus of
      attention that heuristically separates both image and projection data into object
      and background before reconstruction, thereby further reducing the reconstruction
      region of interest. We present experimental results for both methods based on
      mouse data and a parallelized implementation of the SIRT algorithm. The
      computational savings associated with the support region are substantial.
      However, the results for focus of attention are even more impressive in that only
      about one quarter of the computer cycles and memory are needed compared with
      reconstruction of the entire image volume. The image quality is not compromised
      by either method.

PMID- 16953042
TI  - FIRST: Fast Iterative Reconstruction Software for (PET) tomography.
AB  - Small animal PET scanners require high spatial resolution and good sensitivity.
      To reconstruct high-resolution images in 3D-PET, iterative methods, such as OSEM,
      are superior to analytical reconstruction algorithms, although their high
      computational cost is still a serious drawback. The higher performance of modern
      computers could make iterative image reconstruction fast enough to be viable,
      provided we are able to deal with the large number of probability coefficients
      for the system response matrix in high-resolution PET scanners, which is a
      difficult task that prevents the algorithms from reaching peak computing
      performance. Considering all possible axial and in-plane symmetries, as well as
      certain quasi-symmetries, we have been able to reduce the memory requirements to
      store the system response matrix (SRM) well below 1 GB, which allows us to keep
      the whole response matrix of the system inside RAM of ordinary industry-standard
      computers, so that the reconstruction algorithm can achieve near peak
      performance. The elements of the SRM are stored as cubic spline profiles and
      matched to voxel size during reconstruction. In this way, the advantages of 'on
      the-fly' calculation and of fully stored SRM are combined. The on-the-fly part of
      the calculation (matching the profile functions to voxel size) of the SRM
      accounts for 10-30% of the reconstruction time, depending on the number of voxels
      chosen. We tested our approach with real data from a commercial small animal PET
      scanner. The results (image quality and reconstruction time) show that the
      proposed technique is a feasible solution.

PMID- 16953043
TI  - Combining deterministic and Monte Carlo calculations for fast estimation of
      scatter intensities in CT.
AB  - A side effect of increased volume coverage by using multi-row and flat-panel
      detectors in computed tomography (CT) is the concurrently growing contribution of
      scattered radiation to the measured signal. In order to investigate the effect of
      scatter on x-ray projections used for CT imaging, our study aimed at the
      development of a simulation tool for fast calculation of primary and scatter
      intensities. We developed a deterministic method to assess the contribution of
      single-scatter events to the measured signal. The investigation of multiple
      scatter by Monte Carlo simulations showed that it results in a smooth signal as
      compared to single scatter. A hybrid method is proposed in order to optimize the
      performance of the scatter simulation: a fast and exact analytical calculation of
      the single-scatter intensity combined with a coarse Monte Carlo (MC) estimate of
      multiple scatter to reduce overall computational expenses, while assuring an
      acceptable signal quality. The results of the hybrid simulation of total scatter
      were in excellent agreement with the corresponding MC only simulations, thereby
      allowing us to reduce computational time by orders of magnitude. Estimates of two
      dimensional scatter distributions for flat-panel CT imaging took about 30-40 s
      (per projection). The hybrid method provides a realistic simulation of x-ray
      scatter and offers a basis for scatter correction approaches.

PMID- 16953044
TI  - Simulations of localized harmonic motions on a blood vessel wall induced by an
      acoustic radiation force used in ultrasound elastography.
AB  - Many noninvasive techniques have been developed recently to explore the
      mechanical properties of soft tissue. In this paper, dynamic acoustic radiation
      force induced vibrations on a blood vessel wall were simulated using different
      stimulation frequencies and stiffness parameters for the vessel wall. The
      stimulation frequency was varied between 20 Hz and 20 kHz and the stiffness
      parameter (Young's modulus) was varied between 60 kPa and 360 kPa. The vibration
      simulations were computed using a finite-element method in a 3D geometry that
      contained a vessel wall surrounded by soft tissue. The results indicate that
      vibrations caused by acoustic stimulation are sensitive to the changes in
      mechanical properties of the vessel wall and that the vibrations are highly
      dependent on the stimulation frequency and target structure. Therefore,
      measurements of absolute stiffness parameters may not be accurately achieved
      because this method is so dependent on the whole target structure, whereas the
      monitoring of changes during some process may be feasible.

PMID- 16953045
TI  - Fully 4D motion-compensated reconstruction of cardiac SPECT images.
AB  - In this paper, we investigate the benefits of a spatiotemporal approach for
      reconstruction of image sequences. In the proposed approach, we introduce a
      temporal prior in the form of motion compensation to account for the statistical
      correlations among the frames in a sequence, and reconstruct all the frames
      collectively as a single function of space and time. The reconstruction algorithm
      is derived based on the maximum a posteriori estimate, for which the one-step
      late expectation-maximization algorithm is used. We demonstrated the method in
      our experiments using simulated single photon emission computed tomography
      (SPECT) cardiac perfusion images. The four-dimensional (4D) gated mathematical
      cardiac-torso phantom was used for simulation of gated SPECT perfusion imaging
      with Tc-99m-sestamibi. In addition to bias-variance analysis and time activity
      curves, we also used a channelized Hotelling observer to evaluate the
      detectability of perfusion defects in the reconstructed images. Our experimental
      results demonstrated that the incorporation of temporal regularization into image
      reconstruction could significantly improve the accuracy of cardiac images without
      causing any significant cross-frame blurring that may arise from the cardiac
      motion. This could lead to not only improved detection of perfusion defects, but
      also improved reconstruction of the heart wall which is important for functional
      assessment of the myocardium.

PMID- 16953046
TI  - Effect of specimen conditioning on the microarchitectural parameters of
      trabecular bone assessed by micro-computed tomography.
AB  - The best way to preserve the mechanical properties of bone specimens is hydration
      in NaCl, whereas the reference process in microCT analysis is defatting. However,
      for finite element modelling (FEM) it is necessary to use the same bone specimens
      for biomechanical testing and 3D imaging. This study aimed to evaluate the effect
      of sample conditioning on trabecular bone microarchitectural parameters.
      Trabecular bones were analysed by microCT under three successive conditions:
      first, the fatted samples were analysed immersed in NaCl (process N); second,
      they were hydrated for 24 h then imaged without immersion (process H); third, the
      samples were defatted before analysis (process D). The microarchitectural
      parameters bone volume/tissue volume (BV/TV), trabecular spacing (Tb.Sp), number
      (Tb.N) and thickness (Tb.Th) were calculated. Except for BV/TV, there was no
      significant difference between the processes N and D. In process H, BV/TV, Tb.Th
      and Tb.N were higher and BS/BV and Tb.Sp were lower than in process D. Results
      showed that the process D may be replaced by the process N. The process H induced
      significant differences in microarchitectural parameters when compared to process
      D. Nevertheless, this sample conditioning should be used to develop FEM when
      microCT images are to be acquired during compressive testing.

PMID- 16953047
TI  - Ultrasonic propagation in cortical bone mimics.
AB  - Understanding the velocity and attenuation characteristics of ultrasonic waves in
      cortical bone and bone mimics is important for studies of osteoporosis and
      fractures. Three complementary approaches have been used to help understand the
      ultrasound propagation in cortical bone and bone mimics immersed in water, which
      is used to simulate the surrounding tissue in vivo. The approaches used were Lamb
      wave propagation analysis, experimental measurement and two-dimensional (2D)
      finite difference modelling. First, the water loading effects on the free plate
      Lamb modes in acrylic and human cortical bone plates were examined. This
      theoretical study revealed that both the S0 and S1 mode velocity curves are
      significantly changed in acrylic: mode jumping occurs between the S0 and S1
      dispersion curves. However, in human cortical bone plates, only the S1 mode curve
      is significantly altered by water loading, with the S0 mode exhibiting a small
      deviation from the unloaded curve. The Lamb wave theory predictions for velocity
      and attenuation were then tested experimentally on acrylic plates using an axial
      transmission technique. Finally, 2D finite difference numerical simulations of
      the experimental measurements were performed. The predictions from Lamb wave
      theory do not correspond to the measured and simulated first arrival signal (FAS)
      velocity and attenuation results for acrylic and human cortical bone plates
      obtained using the axial transmission technique, except in very thin plates.

PMID- 16953048
TI  - Whole-body voxel phantoms of paediatric patients--UF Series B.
AB  - Following the previous development of the head and torso voxel phantoms of
      paediatric patients for use in medical radiation protection (UF Series A), a set
      of whole-body voxel phantoms of paediatric patients (9-month male, 4-year female,
      8-year female, 11-year male and 14-year male) has been developed through the
      attachment of arms and legs from segmented CT images of a healthy Korean adult
      (UF Series B). Even though partial-body phantoms (head-torso) may be used in a
      variety of medical dose reconstruction studies where the extremities are out-of
      field or receive only very low levels of scatter radiation, whole-body phantoms
      play important roles in general radiation protection and in nuclear medicine
      dosimetry. Inclusion of the arms and legs is critical for dosimetry studies of
      paediatric patients due to the presence of active bone marrow within the
      extremities of children. While the UF Series A phantoms preserved the body
      dimensions and organ masses as seen in the original patients who were scanned,
      comprehensive adjustments were made for the Series B phantoms to better match
      International Commission on Radiological Protection (ICRP) age-interpolated
      reference body masses, body heights, sitting heights and internal organ masses.
      The CT images of arms and legs of a Korean adult were digitally rescaled and
      attached to each phantom of the UF series. After completion, the resolutions of
      the phantoms for the 9-month, 4-year, 8-year, 11-year and 14-year were set at
      0.86 mm x 0.86 mm x 3.0 mm, 0.90 mm x 0.90 mm x 5.0 mm, 1.16 mm x 1.16 mm x 6.0
      mm, 0.94 mm x 0.94 mm x 6.00 mm and 1.18 mm x 1.18 mm x 6.72 mm, respectively.

PMID- 16953049
TI  - Age-dependent organ and effective dose coefficients for external photons: a
      comparison of stylized and voxel-based paediatric phantoms.
AB  - This present study investigates the anatomical realism of conventional stylized
      models of children by comparing organ dose conversion coefficients for the ORNL
      paediatric phantom series with those determined in the UF (University of Florida)
      voxel paediatric phantoms. The latter includes whole-body models of a 9 month
      male, 4 year female, 8 year female, 11 year male and a 14 year male. Of these
      phantoms, the 1 year, 5 year and 10 year ORNL phantoms, and 9 month male, 4 year
      female and 11 year male UF voxel phantoms were selected for side-by-side
      comparisons under idealized external photon irradiation. Organ absorbed dose per
      unit air kerma (Gy/Gy) for various radiosensitive organs and tissues were
      calculated for monoenergetic photons over the energy range of 15 keV to 10 MeV
      and for six irradiation geometries: anterior-posterior (AP), posterior-anterior
      (PA), right lateral (RLAT), left lateral (LLAT), rotational (ROT) and isotropic
      (ISO). Differences in organ dose conversion coefficients for the gonads, bone
      marrow, colon, lung and stomach, to which prominent tissue weighting factors are
      assigned, were depicted and analysed. Two major causes of observed differences
      were suggested: differences in organ shape and position and the differences in
      tissue shielding by overlying tissue regions within the phantoms. Significant
      discrepancies caused by anatomical differences between the two types of phantoms
      are also reported for several organs, and in particular, the thyroid and urinary
      bladder. The results of this study suggest that the paediatric series of ORNL
      phantoms also have less realistic internal organ and body anatomy and that dose
      conversion coefficients from these stylized phantoms should be re-evaluated using
      paediatric voxel phantoms.

PMID- 16953050
TI  - Correction of proton resonance frequency shift temperature maps for magnetic
      field disturbances caused by breathing.
AB  - Respiratory induced resonance offset (RIRO) is a periodic disturbance of a
      magnetic field due to breathing. Such disturbance handicaps the accuracy of the
      proton resonance frequency shift (PRFS) method of MRI temperature mapping in
      anatomies situated nearby the lungs and chest wall. In this work, we propose a
      method capable of minimizing errors caused by RIRO in PRFS temperature maps. In
      this method, a set of baseline images characterizing RIRO at a variety of
      respiratory cycle instants is acquired before the thermal treatment starts.
      During the treatment, the temperature evolution is found from two successive
      images. Then, the calculated temperature changes are corrected for the additional
      contribution caused by RIRO using the pre-treatment baseline images acquired at
      the identical instances of the respiratory cycle. Our method is shown to improve
      the accuracy and stability of PRFS temperature maps in the presence of RIRO and
      inter-scan motion in phantom and volunteers' breathing experiments. Our method is
      also shown to be applicable to anatomies moving during breathing if a proper
      registration procedure is applied.

PMID- 16953051
TI  - Geometry and extension of signal voids in MR images induced by aggregations of
      magnetically labelled cells.
AB  - The ability of magnetic resonance imaging (MRI) to visualize magnetically
      labelled cells has attracted much attention for revealing cellular events. The
      present study addressed the geometry and the extension of signal voids in static
      signal dephasing MRI induced by aggregations of magnetically labelled cells by
      means of a three-dimensional numerical model. The magnetic field distortions
      around spherical cell aggregations were treated as equivalent to those of a
      magnetic dipole. Intravoxel signal dephasing and respective signal voids
      attributed to these field inhomogeneities were computed. Effects of cell
      concentration on the signal void in the plane of view were evaluated in terms of
      dipole magnetization. Signal void characteristics were scrutinized systematically
      for fundamental sequence parameters including echo time, voxel size and plane-of
      view orientation. For all variables examined, significant changes in geometry as
      well as extension of signal voids were demonstrated. The results are of crucial
      importance to optimize and interpret MR images with regard to spatial accuracy as
      well as sensitivity to detect aggregations of labelled cells in vitro or even in
      vivo. It is anticipated that the dependence of the extension of signal voids on
      the local magnetization may be valuable for quantifying labelled cells.

PMID- 16953052
TI  - Mean time-of-flight of photons in transillumination measurements of optically
      anisotropic tissue with an inclusion.
AB  - We study the effect of optical anisotropy on the mean time-of-flight of photons
      in a slab of turbid medium containing an inclusion whose optical properties
      differ from those of the bulk. For this analysis the difference in the mean time
      for a photon introduced into the slab to reach a specified target point with and
      without the inclusion is calculated. This difference is defined to be a measure
      of the contrast. The theoretical model is based on a continuous-time random walk
      on a lattice, which can be solved exactly and furnishes an exact expression for
      the contrast. Qualitative and quantitative characteristics of the contrast are
      analysed as functions of the geometric configuration of the system components
      (locations of the source, the inclusion and the detector), parameters that
      specify the optical anisotropy of the medium, and either the scattering
      properties of the inclusion or the lifetime of the small fluorophore in the case
      of the time-resolved fluorescence experimental configuration.

PMID- 16953053
TI  - Infective endocarditis and dental procedures: evidence, pathogenesis, and
      prevention.
AB  - Infective endocarditis is a serious infection occurring on the endothelial
      surfaces of the heart, especially at the valves. Oral commensal bacteria are the
      important etiologic agents in this disease. Common dental procedures, even non
      surgical dental procedures, can often cause bacteremia of oral commensals.
      Periodontally diseased patients are at risk from bacteremia even after brushing
      the teeth. Bacteremia itself rarely affect healthy people but they can result in
      mortal infective endocarditis in those who have a predisposed risk for this
      disease, such as those with heart valve diseases, pacemaker implantation, etc.
      Infective endocarditis is thus established when all the 3 conditions are present
      simultaneously, i. e., 1) a predisposing impairments in the heart, 2) the
      introduction of bacteria into the bloodstream, and 3) the virulence of bacteria.
      Antibiotics have to be adequately used to prevent this infection, however, their
      frequent uses generates drug-resistant mutant bacteria, which is a serious social
      problem. The development of novel alternative drugs to be used instead of the
      current antibiotics is thus highly desired. We are now using several types of
      combinatorial peptide libraries to search for small size molecular mimetics that
      can interfere with the adhesion of bacteria to the target organ. The use of such
      peptides is expected to lead to the development of compounds for a novel
      preventive drug which does not kill bacteria, thus making it safer and less
      likely to generate drug-resistant mutants.

PMID- 16953054
TI  - New trend of MRI diagnosis based on the function and metabolism in the central
      nervous system.
AB  - The movement of a subject is a major problem in MRI experiments and diagnosis. At
      first, this review introduces a new technology named the "Propeller Technique"
      which can improve the motion artifact by changing the data sampling method in the
      K trajectory. Our experience of a case who underwent measurement by Propeller
      technique is reported and the effect of this technique is explained. One of the
      recent hot topics is the appearance of the clinical 3T MR instrument, with its
      characteristic differences from that at 1.5T. The advantage of 3T is that it
      facilitates the evaluation of functional and metabolic information using MR
      spectroscopy (MRS) and functional MRI. The application of proton MRS in clinical
      cases is shown and the standard method to use proton MRS in a clinical setting is
      demonstrated. Furthermore, the new techniques, which can measure important
      metabolites in small amount such as neurotransmitters, was developed using a high
      signal to noise ratio and frequency resolution, which are advantages of 3T.

PMID- 16953055
TI  - Impact of dietary and lifestyle on vitamin D in healthy student girls aged 11-15
      years.
AB  - OBJECTIVE: To study daily intake of calcium, phosphorus and vitamin D, to
      determine the biochemical findings of rickets and the effect of sunlight exposure
      and vitamin D supplementation in school girls with hypovitaminosis D. METHODS: A
      cross-sectional study was conducted on school girls aged 11-15 years selected
      randomly from various areas of Tehran, Iran. Dietary information and amount of
      sunlight exposure were estimated by a 7 day recalling method using self-reported
      questionnaire. Hypovitaminosis D defined as low serum 25-hydroxyvitamin D
      concentration with two or more others abnormal biochemical findings. Girls with
      hypovitaminoses D were randomly divided into two groups. The faces and hands of
      girls in group 1 were exposed to sunlight for one hour per day for twenty days,
      while those in group 2 were administered vitamin D capsules, 50,000 IU per day
      for the same period. RESULTS: four-hundred fourteen girls evaluated, mean daily
      calcium intake, sunlight exposure and vitamin D acquirement were 360 mg, 10
      minutes and 119 IU, respectively. Mean serum 25-hydroxyvitamin D concentration
      was 30 ng/ml among all girls whereas in 15 (3.63%) of 414 girls was 7.8 ng/ml.
      Abnormal biochemical findings in these girls included hypocalcemia (n=4),
      hypophosphatemia (n=5), raised serum alkaline phosphatase (n=13), and parathyroid
      hormone (n=15). After intervention, mean serum 25-hydroxyvitamin D concentration
      in sunlight exposure (n=8) and vitamin D (n=7) supplementation increased to
      14.4+/-4 ng/ml and 23+/-4 ng/ml respectively. There was a significant difference
      between the two groups (p<0.05). CONCLUSION: Vitamin D deficiency developed in
      rapid growth period of girls without clear clinical rickets in sunny temperate
      climate city in Iran which vitamin D supplementation improved biochemical
      findings better than sunlight exposure.

PMID- 16953056
TI  - Challenge of psychiatric rehabilitation for patients with long-term
      hospitalizations using the Nirje's normalization principles as a valuation
      standard: two case studies.
AB  - This research investigates the current care of hospitalized, chronically mentally
      ill persons to determine to what extent current hospitalization supports Nirje's
      principles of normalization. We propose that care-providers try to incorporate
      rehabilitation programs that help the patients acquire the pattern and rhythm of
      living necessary for them to live in the community in their daily hospital life
      rather than to fit the patients into hospital rules or schedule. Therefore, care
      providers must look back on their own views of the humanity, disabled people, and
      support and may have to change them if necessary. It is important that care
      providers do not give up having psychiatric patients not give up restoration of
      normal social living. To develop such individual attempts into rewarding
      activities, it is necessary to set goals in the hospital and to let an
      interdisciplinary team work to achieve them. Moreover, the situation is expected
      to change if efficient care management is implemented to support psychiatric
      patients in the community. High-quality care to realize independent living of
      patients in the community including collection and distribution of information,
      management of symptoms, assistance for self-care, and psychological education is
      provided at hospitals that maintain the idea of, and strong belief in, providing
      high-quality care for returning patients to the community. The findings of this
      study will provide insights into how to design better hospitalization and/or
      community care for the mentally ill.

PMID- 16953057
TI  - A/G heterozygote of the A-3826G polymorphism in the UCP-1 gene has higher BMI
      than A/A and G/G homozygote in young Japanese males.
AB  - UCP-1 is suggested to have important roles for thermogenesis and energy
      expenditure. To elucidate whether the A-3826G polymorphism that is located in the
      5' flanking region of the UCP-1 gene has roles in healthy young people, the
      polymorphism was genotyped among 251 young Japanese men whose mean age is 22.7
      years old. We analyzed relationship between the A-3826G polymorphism and body
      mass index (BMI) or six biochemical parameters, serum concentration of total
      cholesterol (TC), high density lipoprotein (HDL) cholesterol, triglyceride (TG),
      asparatate aminotransferase (AST), alanine aminotransferase (ALT), fasting plasma
      glucose. The genotype frequencies were observed at the frequencies of 24.3% for
      AA, 48.2% for AG and 27.5% for GG, respectively. When BMI and the biochemical
      parameters were compared by ANOVA among individuals with each genotype, the
      statistical difference was observed only for BMI (P=0.016). Bonferroni's test
      demonstrated that the men with the AG genotype have higher BMI than those with
      the AA genotype (22.4+/-2.8 vs. 21.4+/-2.2) (P=0.04). The individuals with the AG
      genotype also showed trend to have higher BMI than those with the GG, although
      the difference was not statistically apparent (22.4+/-2.8 vs. 21.5+/-2.3)
      (P=0.07). Our results indicated that the young healthy Japanese men with the AG
      heterozygote showed higher BMI than those with other genotypes.

PMID- 16953058
TI  - Indicators for blood glucose control in diabetics with end-stage chronic renal
      disease: GHb vs. glycated albumin (GA).
AB  - Diabetics with end-stage renal disease (ESRD) exhibit abnormal life span of
      erythrocytes, and thus, HbAlc is not necessarily a good indicator for blood
      glucose control. The present study was conducted to reaffirm this point and
      determine whether glycated albumin (GA) can be used instead of HbAlc. The
      following three groups of patients with diabetes served as subjects: 49
      predialysis patients with ESRD (predialysis group), 37 patients with ESRD on
      dialysis (dialysis group), and 40 patients without nephropathy (non-dialysis
      group). The profile set mean blood glucose was calculated by measuring blood
      glucose levels seven times a day. The relationship of profile set mean blood
      glucose with HbAlc and GA levels was then investigated. Corrected HbAlc levels
      were calculated by applying the profile set mean blood glucose of each ESRD
      patient to the regression formula for the HbAlc of non-dialysis patients. The
      actual and corrected HbAlc levels for the predialysis patients were 5.4+/-1.1 and
      7.9+/-1.1%, respectively, while those for the dialysis patients were 5.6+/-1.0
      and 7.5+/-0.9%, respectively (p<0.0001). The changes in GA levels in relation to
      the blood glucose control in the dialysis patients matched those in non-dialysis
      patients. HbAlc levels for diabetics with ESRD were lower than indicated by their
      blood glucose control. When assessing blood glucose control based solely on
      HbAlc, erroneous results may be obtained. In such cases, GA may be used instead
      of HbAlc.

PMID- 16953059
TI  - Evaluation of the effects of mastication and swallowing on gastric motility using
      electrogastrography.
AB  - OBJECTIVES: The influence of mastication and swallowing on gastric motor function
      was evaluated by electrogastrography (EGG) and abdominal ultrasonography.
      METHODS: The subjects were 30 elderly patients with tubal feeding without
      mastication and swallowing (T group) and 30 elderly controls who processed food
      by mastication and swallowing (C group). Gastric motor function was
      percutaneously examined before and after the ingestion of 250 ml of a liquid diet
      using an electrogastrograph (NIPRO EGG, A and D, Tokyo, Japan). The cross
      sectional area of the gastric antrum was measured at 1 and 30 min after the start
      of ingestion of the liquid diet by external ultrasonography of the abdomen, and
      the gastric excretion function was evaluated. Furthermore, the spectral analysis
      of heart rate variability was performed using Holter electrocardiograms before
      and after ingestion. The low frequency power (LF power, 0.04-0.15 Hz), high
      frequency power (HF power, 0.15-0.40 Hz), and the LF/HF ratio were determined.
      RESULTS: The peak amplitude at 3 cycles per minute (cpm) was significantly
      increased after ingestion in the C and T groups (p<0.05), and the ratio of
      increase was significantly lower in the T group (p<0.05). The mean amplitude for
      the brady-gastria and tachy-gastria was significantly higher in the T group than
      in the C group (p<0.05). The gastric excretion function, as evaluated by external
      ultrasonography of the abdomen, was significantly lower in the T group than in
      the C group (p<0.05). An analysis of heart rate variability demonstrated that the
      HF power, a parameter of parasympathetic activity, after ingestion was
      significantly higher in the C group than in the T group (p<0.05). No changes in
      LF power or LF/HF ratio, parameters of sympathetic activity, were induced by
      ingestion in either the C or T groups. CONCLUSIONS: The parasympathetic nerve
      dominantly controls gastric motor function, but autonomic nervous activity is
      reduced in patients who are unable to masticate and swallow food, resulting in
      adverse effects on gastric motor function and excretion function. Mastication and
      swallowing not only prepare food for passage from the oral cavity to the
      esophagus but are also important in terms of subsequent events that occur in
      stomach. It has been proposed that autonomic nervous activity might be involved
      in mastication and swallowing.

PMID- 16953060
TI  - ALK7 is a novel marker for adipocyte differentiation.
AB  - Transforming growth factor-beta (TGF-beta) family members regulate a variety of
      cellular functions and play important roles in cell differentiation. Activin
      receptor-like kinase 7 (ALK7), a receptor for TGF-beta family members, was
      initially cloned from rats as an orphan receptor and has been recently shown to
      be a type I receptor for nodal, activin B and activin AB. ALK7 is expressed not
      only in neurons, but also in insulin-producing islet beta cells and white and
      brown adipose tissues; however, the specific functions of ALK7 in these tissues
      are not known. In order to test whether ALK7 is involved in adipocyte
      differentiation, we analyzed its expression during adipocyte differentiation.
      ALK7 expression was detected in the late phase of adipocyte differentiation by
      reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting and
      immunofluorescence staining in 3T3-L1 cells. We also detected the expression of
      ALK7 by RT-PCR in stromal vascular fraction (SVF) cells. These results indicated
      that ALK7 is a novel marker specifically expressed during the late phase of
      adipocyte differentiation. Furthermore, our results suggest the possible
      involvement of nodal or activin B in adipocyte differentiation.

PMID- 16953061
TI  - A histochemical and immunohistochemical investigation of guanase and nedasin in
      rat and human tissues.
AB  - Human guanase is known as a specific enzyme in the liver, kidney, and brain.
      However, its functional significance remains poorly understood. In addition,
      interestingly, a different organ distribution between humans and rats was
      suggested. Here, we performed immunohistochemical staining with anti-human
      nedasin (neuronal and endocrine discs large/SAP102 associated protein), whose
      sequence was identical to that of guanase, antibody and histochemical staining
      for guanase in normal tissues of rat and human liver, kidney, and small
      intestine, and compared the results. Guanase activity was observed uniformly in
      the rat hepatocytes, biliary epithelium and vascular endothelium cells, while it
      was localized to the hepatocytes and biliary epithelium in the human liver. When
      the histochemical staining for guanase and the immunohistochemical staining for
      nedasin were compared, the stained regions were different in the rat liver but
      were almost consistent in all human tissues. Totally consistent staining results
      were also obtained between rats and humans in the other organization except the
      liver. Based upon the research reports to date, the experiments on guanase and
      nedasin in rat organs performed in this study are considered to have important
      implications in the investigation of their physiological significance.

PMID- 16953062
TI  - Soy protein diet prevents hypermethioninemia caused by portacaval shunt in rats.
AB  - In hepatic disorders, abnormal plasma amino acid profiles are observed. In this
      study, we examined whether soy protein isolate (SPI) improved plasma methionine
      concentration in the model animals. Portacaval shunt (PCS) increased alanine
      aminotransferase (ALT) activity and methionine concentration in blood of rats fed
      a 40% casein diet supplemented with 0.6% methionine (casein-M diet). A 40% SPI
      diet supplemented with 1.28% methionine (SPI-M diet), which contained the same
      amount of methionine as that in 40% casein-M diet, normalized plasma ALT activity
      and methionine level in PCS rats. These effects of a SPI diet may be due to its
      amino acid composition, since an amino acid mixture diet mimicking a 40% SPI-M
      diet was also effective to hypermethioninemia of PCS rats. To find key enzymes
      for the beneficial effect of soy protein, we examined effects of a 40% SPI-M or
      casein-M diet on the activities of three methionine-metabolizing enzymes in liver
      of PCS rats. A SPI-M diet stimulated only the activity of cystathionine gamma
      lyase, compared with a casein-M diet. A SPI diet has a preventive effect on
      hypermethioninemia, at least in part, by stimulating cystathionine gamma-lyase
      activity in liver and may be used for nutritional management of liver disorders
      with hypermethioninemia.

PMID- 16953063
TI  - Histochemical and immunohistochemical investigation of guanase and nedasin in
      human tissues.
AB  - Guanase is known as an enzyme released from the liver. Recently, cloning and
      sequencing of the guanase gene were reported. In addition, almost simultaneously,
      it was reported that an unknown protein that binds to neuronal and endocrine
      lethal(1)-discs large (NE-dlg), one of the membrane-associated guanylate kinase
      homologues (MAGUK) family proteins involved in synaptic connection between
      neurons, was cloned and named nedasin (NE-dlg associated protein), whose sequence
      was almost identical to that of guanase. We immunostained fresh frozen sections
      of surgically removed human liver, kidney, and small intestine with anti-nedasin
      antibody, and simultaneously performed histochemical staining for guanase for
      comparison. Histochemically, guanase activity was observed in the cytoplasm of
      hepatocytes and biliary epithelium on the liver, in the mucosal epithelium on the
      small intestine, and in the proximal tubule on the kidney. Immunohistochemically,
      a brown discoloration due to DAB oxidation was seen in the cytoplasm of
      hepatocytes and biliary epithelium on the liver, in the proximal tubule but in
      the distal tubule a little on the kidney, in the mucosal epithelium on the small
      intestine. The stained region of the liver and the small intestine were different
      from that of the kidney. The different staining properties dependent on the
      organs were considered to be due to different isozymes. The physiological
      significance of guanase may vary with the isozymes, further studies are
      considered necessary.

PMID- 16953064
TI  - Morphological study on biologically distinct vpx/vpr mutants of HIV-2.
AB  - We have previously shown that human immunodeficiency virus type 2 (HIV-2) without
      functional vpx and vpr genes is severely defective for viral growth in
      lymphocytic cells, and suggested that the virions produced in the absence of Vpx
      and Vpr are critically damaged. To examine the nature of replication-defect for
      the vpx/vpr double mutant, we quantitatively and morphologically studied the
      virions produced in cells transfected or infected with wild type clone, single
      (vpx and vpr mutants) or the double mutant. While no significant difference in
      virion production was found for various virus clones in transfected cells, a
      major growth retardation in infected cells was readily observed for the vpx and
      vpx/vpr mutants. In particular, no viral growth was detected for the double
      mutant. By contrast to the very distinct growth characteristics of the three
      mutant clones, no appreciable difference in virion morphology was noted. These
      results indicated that Vpx and Vpr of HIV-2 may cooperatively contribute to
      virion infectivity without affecting virion morphogenesis.

PMID- 16953065
TI  - The use of electrogastrography and external ultrasonography to evaluate gastric
      motility in Crohn's disease.
AB  - Although Crohn's disease is associated with various digestive symptoms, there
      have been few reports on gastric motility. In this study, we conducted a study of
      gastric motility in Crohn's disease using 20 healthy subjects (N group) and 15
      patients with Crohn's disease (C group) by electrogastrography (EGG) using a
      Nipro electrogastrograph. An EGG was recorded for 30 minutes in a fasting state
      and after ingestion of 300 ml of a liquid meal. As an index of gastric emptying,
      the rate of change in the cross-sectional area of the gastric antrum was measured
      1 and 15 minutes after ingestion of the liquid meal by external ultrasonography.
      In an EGG frequency analysis, waveforms with a peak of 3 cycles/minute (cpm) were
      noted in the N group, and the peak amplitude increased significantly after the
      ingestion of food. In the C group, division of the normal-gastria component was
      noted after the ingestion of food in 5 patients (33.3%). In a comparison of the
      peak amplitudes of fasting brady-gastria, normal-gastria, and tachy-gastria
      between the N and C groups, the peak amplitude was significantly increased in
      normal-gastria in the N group, and in brady-gastria and tachy-gastria in the C
      group. In a comparison of the rates of food ingestion-induced changes in the peak
      amplitudes for brady-gastria, normal-gastria, and tachy-gastria between the N and
      C groups, the peak amplitudes were significantly increased in normal-gastria in
      the N group, but not in the C group. In the case of gastric emptying investigated
      by external ultrasonography, the rate of food ingestion-induced change in the
      cross-sectional antrum area was significantly lower in the C group (50.5+/-9.2%)
      than in the N group (65.0+/-8.5%). For gastrointestinal motility, a 3 cpm normal
      gastria represents efficient gastric motility. In the C group, the peak
      amplitudes of brady-gastria and tachy-gastria were significantly increased, but
      were low in normal-gastria in the fasting EGG, postprandial division of the
      normal-gastria component was noted, and the rate of food ingestion-induced
      increase in the normal-gastria peak amplitude was significantly lower than that
      in the N group, suggesting that patients with Crohn's disease have a functional
      abnormality in, not only the small and large intestine, but also the stomach.

PMID- 16953066
TI  - Technetium-99m sestamibi single photon emission computed tomography findings
      correlated with P-glycoprotein expression in pituitary adenoma.
AB  - The aim of this study is to evaluate whether the technetium-99m sestamibi
      ((99m)Tc-MIBI) single photon emission computed tomography (SPECT) characteristics
      of pituitary adenomas might be correlated with cavernous sinus invasion,
      proliferative potential or the multidrug-resistance (MDR-1) gene product P
      glycoprotein (Pgp) expression in pituitary adenomas. Fifteen patients with
      pituitary adenomas, including 10 nonfunctioning adenomas, two prolactinomas, two
      GH producing adenomas, and one ACTH producing adenomas was investigated for this
      study. SPECT images with (99m)Tc-MIBI were acquired 15 minutes (early) and 3
      hours (delayed) after injection. The tumor-to-normal brain ratio was calculated
      both early (ER) and delayed (DR) images. Retention index (RI) was calculated
      using the following formula: (DR-ER)/ERx100%. The pituitary adenomas specimens
      were examined by immunohistochemistry using anti-Pgp and MIB-1 monoclonal
      antibodies.(99m)Tc-MIBI SPECT findings were not related to MIB-1 labeling index
      or cavernous sinus invasion. (99m)Tc-MIBI SPECT RI (-38.55+/-20.77) of the Pgp
      positive group was significantly lower than that (-15.78+/-19.40) of Pgp-negative
      group (p=0.0494). No significant difference was observed in the ER and DR of
      (99m)Tc-MIBI SPECT between Pgp-positive and negative groups. Our study suggests
      that although (99m)Tc-MIBI SPECT is not useful to evaluate the proliferative
      potential or cavernous sinus invasion of pituitary adenomas. (99m)Tc-MIBI SPECT
      could predict anti-cancer drug resistance related to the expression of Pgp in
      pituitary adenomas.

PMID- 16953067
TI  - Clinical trials for drug approval: a pilot study of the view of doctors at
      Tokushima University Hospital.
AB  - The development of new and useful pharmaceutical drugs is essential in order to
      improve the quality of drug therapeutics. Clinical trials play a central role in
      drug development. Over time, the clinical trial infrastructure has improved and
      is now integrating the contribution of clinical research coordinators (CRC).
      Nevertheless, the attitude of doctors towards clinical trials still favors
      conventional/historical methodologies. In the present study, we explored the view
      of doctors towards clinical trials for drug development, in order to improve
      communication among participants, sponsors, and investigators.A questionnaire was
      designed for this pilot study. The questionnaire included general attitudes,
      difficult points, the benefit of doctors in participating as investigators,
      special attention requirements, and the expected role of CRC in clinical trials
      for drug approval. In addition, the appropriate use of the outpatient clinic was
      examined. The questionnaire was provided to doctors in each department of
      Tokushima University Hospital in 2000 and 2004. Because of the small number of
      subjects included in this pilot study, no statistical analysis is presented. A
      total of 89 (81%) and 62 (56%) doctors among 110 responded to the survey in 2000
      and 2004, respectively. Inquiries about the familiarity of the physicians with
      clinical trials for drug approval revealed that 84% in 2000 and 66% in 2004 were
      aware of such trials. The attitude towards participating as investigators in the
      clinical trials was favorable, with a response of 66% in 2000 and 58% in 2004.
      Patients' refusal and the informed consent process were considered difficult
      areas by many doctors. Expected roles of CRC included activities based on the
      nurse's specialty. Although many doctors agreed to take care of the study
      participants separately from the clinical practice, they lacked the time to do
      so. In spite of the doctors' workload reduction by introduction of the CRC
      concept, their views regarding clinical trials for drug approval remain
      conventional. Further refinement in the support process by CRC should be
      considered in our hospital, and the views of the doctors should be investigated
      in a larger study, in order to promote clinical trials for drug approval in
      Japan.

PMID- 16953068
TI  - Soluble matrix from osteoblastic cells induces mineralization by dental pulp
      cells.
AB  - Dental pulp cells have a capacity to differentiate into mineralization-inducing
      cells. To clarify the molecular mechanism, we established an in vitro
      mineralization-inducing system by rat clonal dental pulp cell line, RPC-C2A, and
      tried to purify a mineralization-inducing factor in conditioned medium (CM) from
      pre-osteoblastic MC3T3-E1 cells. The active factor was impermeable to an
      ultrafiltration membrane, and sedimented by ultracentrifugation. The sedimented
      factor was found as a needle-like structure about 1.3 microm in average length as
      observed by transmission electron microscopy. The factor contained type I
      collagen, suggesting not a matrix vesicle, but a soluble matrix. The
      mineralization-inducing activity was also detected in CM from primary culture of
      rat calvaria (RC) cells. These results suggested that the soluble matrices from
      osteoblastic cells serve, at least in part, as differentiation-inducing agents.

PMID- 16953069
TI  - Nateglinide with glibenclamide examination using the respiratory quotient (RQ).
AB  - PURPOSE: The respiratory quotient (RQ) is useful for evaluating glucose and lipid
      metabolism in vivo. We previously reported that the RQ value, even after fasting,
      was high in diabetics being treated with sulphonylurea (SU), which might explain
      the accumulation of fat, leading to weight gain in such individuals. In the
      present study, we measured the RQ in type II diabetic patients who were being
      treated with a rapid-onset/short-duration insulinotropic agent, nateglinide, and
      compared it with those being treated with SU. METHODS: A glucose tolerance test
      was performed in 20 patients with type II diabetes mellitus treated with
      nateglinide and in 14 patients treated with SU, and the RQ was simultaneously
      measured. RESULTS: The RQ values in the patients treated with nateglinide, were
      similar to those in healthy adults, but was lower than in those treated with SU.
      No weight gain was observed in patients treated with nateglinide. CONCLUSION: A
      significant weight gain was reported in subjects treated with SU, accompanied by
      an increase in RQ. However, weight gain was less frequent in diabetics treated
      with nateglinide.

PMID- 16953070
TI  - Risk factors associated with soft coronary artery plaques in Japanese, as
      determined by 16 slice multidetector-row computed tomography.
AB  - PURPOSE: The acute coronary syndrome is often caused by the rupture of plaques
      and thrombus formation even without significant stenosis, and patients with soft
      plaques, but without significant stenosis evidenced by coronary angiography
      (CAG), often develop an acute coronary syndrome. To address this discrepancy, a
      qualitative diagnosis of coronary plaques using a 16 slice multidetector-row CT
      was conducted. METHODS AND RESULTS: Volume rendering and cross-sectional MPR
      images were obtained. Based on the CT values, plaques on the coronary artery wall
      were classified as lipid-rich soft plaques (CT value<50 HU) and non-soft plaques
      (>50 HU).A significant correlation was observed between the percent stenosis
      determined in cross-sectional MPR images and those determined by CAG (r=+0.92,
      p<0.01). Diffuse plaques with CT values of less than 50 HU often caused stenosis
      at level of 75% or less, which were not indicated by percutaneous transluminal
      coronary angioplasty. CONCLUSIONS: Although diffuse soft plaques with CT values
      less than 50 HU are not an indication of intervention, a risk of an acute
      coronary syndrome exists, due to rupture. These soft plaques must be stabilized
      by treatment even when they do not cause significant stenosis, and MDCT is
      considered to be useful for their evaluation.

PMID- 16953071
TI  - Poorly differentiated neuroendocrine cell carcinoma of the rectum: report of a
      case and literal review.
AB  - A 56-year-old man was admitted to our hospital because of anal bleeding.
      Colonoscopy and barium enema revealed type 4 tumor in the rectum. Biopsy revealed
      poorly differentiated adenocarcinoma. Low anterior resection with total
      mesorectal excision and lymph node dissection was performed. In
      immunohistochemical staining, chromogranin A and synaptophysin were positive at
      major lesion, and CEA were focal positive. The resected tumor was diagnosed
      pathologically as neuroendocrine cell carcinoma. The Ki-67 labeling index (LI)
      was 87.8%, so proliferative activity and potential malignancy was very high.
      Multiple metastatic tumors appeared in pelvis and lung eight months after
      operation. Treatment for neuroendocrine cell carcinoma of the rectum was
      controversial. Surgical resection and adjuvant chemotherapy might be one of the
      methods for gastrointestinal neruroendocrine cell carcinoma.

PMID- 16953072
TI  - A case of early relapsed multiple lung metastases after esophagectomy
      successfully treated with S-1/cisplatin therapy after docetaxel/5
      fluorouracil/cisplatin therapy.
AB  - A 55-year-old-male patient underwent subtotal esophagectomy for esophageal cancer
      (pT1b, N0, M0, stage II) in April 2005. The patient received postoperative
      chemotherapy (docetaxel 40 mg/body, 5-fluorouracil 750 mg/body, cisplatin
      10mg/body: administered every 4 weeks) for 3 months. Six months postoperatively,
      routine follow up CT demonstrated multiple metastatic tumors in the bilateral
      lungs. Under the diagnosis of multiple lung metastases, the patient was
      hospitalized and received intensive chemotherapy with docetaxel 40 mg/week (day
      1), 5-fluorouracil 500 mg/day (days 1-5), cisplatin 10 mg/day (days 1-5). After
      two weeks administration, the patient eagerly hoped for outpatient treatment. The
      treatment was changed to outpatient chemotherapy with S-1 100 mg/day (continuous
      administration for 3 weeks followed by rest for 1 week) and cisplatin 20 mg/every
      week. The treatment enabled the patient to keep working. Follow up CT showed
      disappearance of all tumors two months after TS-1/cisplatin chemotherapy. There
      were no obvious signs of recurrence 5 months after chemotherapy. The S
      1/cisplatin therapy in the outpatient was thought to be one of the effective
      treatments in maintaining quality of life for the patient.

PMID- 16953073
TI  - Rapid-growing solitary necrotic nodule of the liver.
AB  - The solitary necrotic nodule of the liver is an uncommon nonmalignant lesion with
      an uncertain etiology. The lesion was defined as a nodule with a completely
      necrotic core and fibrous capsule etc. and without a consistency of viable cells.
      The characteristic features of this benign lesion on the imaging modalities are
      similar to the metastatic tumor. In this paper we discuss the case of a rapid
      growing solitary necrotic nodule of the liver occurring in a patient with chronic
      renal failure on hemodialysis. The lesion located on the left median lobe of the
      liver had rapidly enlarged in diameter in the last seven months. Despite some
      examinations by imaging modalities to confirm the preoperative diagnosis, we were
      unable to visually confirm. Several histological examinations using a needle
      biopsy specimen were performed, but the diagnosis was all necrotic tissue.
      However, we recommended an extended left hepatic lobectomy for this rapid-growing
      lesion since cholangiocarcinoma with necrosis could be hardly differentiated.
      Permanent histology revealed that the lesion was solitary necrotic nodule. We
      consider that permanent histology of the entire lesion is possibly the only
      accurate method of diagnosis. Since the solitary necrotic nodule does not
      indicate malignancy, hepatic resection should be performed.

PMID- 16953074
TI  - Cardiovascular effects of continuous propofol infusion in horses.
AB  - We examined the influence of propofol infusion on cardiovascular system at the
      rate of 0.14, 0.20 and 0.30 mg/kg/min in six adult Thoroughbred horses. The
      cardiovascular parameters were heart rate (HR), mean arterial pressure (MAP),
      mean right atrial pressure (MRAP), stroke volume (SV), cardiac output (CO),
      systemic vascular resistance (SVR), pre-ejection period (PEP) and ejection time
      (ET). In order to keep the ventilation conditions constantly, intermittent
      positive pressure ventilation was performed, and the partial arterial CO(2)
      pressure was maintained at 45 to 55 mmHg during maintenance anesthesia. SV showed
      a significant dose-dependent decrease however, CO did not show significant
      change. SVR decreased significantly at higher dose. PEP was prolonged and PEP/ET
      increased significantly at the highest dose. From these results, it became clear
      that SV decreases dose-dependently due to decrease of cardiac contractility
      during anesthesia with continuous propofol infusion in horses. On the other hand,
      since MAP and CO did not show significant changes, total intravenous anesthesia
      with propofol was suggested to be suitable for long-term anesthesia in horses.

PMID- 16953075
TI  - Immunohistochemical detection of p27 and p21 proteins in canine hair follicle and
      epidermal neoplasms.
AB  - Trichoblastomas, trichoepitheliomas, and squamous cell carcinomas in the skin of
      dogs were analysed by immunohistochemistry for the nuclear expression of p27, p21
      and proliferating cell nuclear antigen (PCNA). High levels of p27 were present in
      trichoepitheliomas and trichoblastomas compared with squamous cell carcinomas.
      Detectable p21 was found in trichoepitheliomas and squamous cell carcinomas, but
      trichoblastomas had low level of p21 nuclear reactivity. Low levels of PCNA were
      detected in trichoepitheliomas and trichoblastomas compared with squamous cell
      carcinomas. The results suggested that nuclear p27 acts as a cyclin-dependent
      kinase (CDK) inhibitor in trichoepitheliomas and trichoblastomas. Nuclear p21
      expression is involved in the induction of epithelial differentiation and seems
      to be unrelated to CDK inhibition.

PMID- 16953076
TI  - Drop of egg production in chickens by experimental infection with an avian
      metapneumovirus strain PLE8T1 derived from swollen head syndrome and the
      application to evaluate vaccine.
AB  - Decreases in egg production and increased incidence of abnormal eggs due to
      malformation of egg shells were observed in specific pathogen free (SPF) 173-day
      old laying hens inoculated intravenously with an avian metapneumovirus (aMPV)
      strain PLE8T1. This strain was derived from an isolate from broiler birds
      exhibiting swollen head syndrome (SHS). Some SPF birds inoculated with the virus
      showed, slight diarrhea without any respiratory symptoms. Thus, the PLE8T1 strain
      was used as a challenge virus to evaluate efficacy of aMPV vaccines. SPF chickens
      which received a live attenuated aMPV vaccine (NEMOVAC; Merial) at 7 or 77 days
      old and an inactivated aMPV vaccine (OVO-4; Merial) at 105 days old were
      protected against poor egg production caused by the challenge with the PLE8T1
      strain. Thus, aMPV, the PLE8T1 strain passaged 22 times after isolation, from
      birds exhibiting SHS, could induce a drop in egg production in laying hens
      accompanied by malformation of egg shells. It was suggested that this challenge
      system could be applied to evaluate the efficacy of aMPV vaccine.

PMID- 16953077
TI  - A comparison of the behavioral profiles of purebred dogs in Japan to profiles of
      those in the United States and the United Kingdom.
AB  - To clarify the behavioral profiles of 56 pure breeds of dogs in Japan, 96 small
      animal veterinarians participated in a questionnaire survey using the same
      criteria as in preceding studies conducted in the United States and the United
      Kingdom. We found significant differences among breeds in all behavioral traits
      examined. In addition, gender differences were revealed in terms of aggression to
      dogs, territorial defense, excitability, general activity, dominance over owner,
      destructiveness, watchdog barking, and snapping at children, which were all rated
      higher in males than females, whereas obedience training and housebreaking ease
      were rated higher in females. No gender differences were evident in playfulness,
      excessive barking, or affection demand. Using factor analyses, "aggressiveness",
      "reactivity", and "trainability" were determined to be consistent with results
      found in the US and UK surveys. On the basis of these factor scores, seven groups
      of breeds were determined by cluster analysis to compare to the US survey; 22 of
      the 38 breeds common with the US survey were categorized into the same groups as
      those in that survey. The results demonstrated differences in canine behavioral
      predisposition among breeds and between genders. The similarity in the results
      between our study and previous surveys, which involved distinct geographical
      locales, suggests that the genetic basis of breed-specific temperamental traits
      is manifested irrespective of the cultural or regional identities of the owners.

PMID- 16953078
TI  - Retinoids induce growth inhibition and apoptosis in mast cell tumor cell lines.
AB  - Retinoids are well recognized as promising antitumor agents in humans. However,
      there have only been a few reports about the effect of retinoids in canine
      cancers. To investigate the antitumor effect of retinoids on mast cell tumors
      (MCT), inhibitory effect on cell growth and induction of apoptosis were examined
      in vitro. Although sensitivity of these cells differed among the cells, the
      growth of three MCT cell lines (CoMS, CM-MC and VI-MC) were inhibited dose
      dependently when they were treated with retinoids. FACS analysis of PI-stained
      nuclei revealed an apoptotic fraction in CM-MC cells about 30% when treated with
      retinoids, while those of control cells were less than 5%. Caspase-3 activation
      was observed after retinoid treatment in CM-MC cells. This was confirmed by
      inhibiting the retinoid-induced apoptosis using the pan-caspase inhibitor, ZVAD
      FMK. Both retinoid receptors, RARs and RXRs, were detected by immunoprecipitation
      followed by western blot analysis in all the three MCT cells. These data suggests
      that retinoids inhibit the growth of MCTs partly through apoptosis, and this
      growth inhibition by retinoids may be mediated by RARs and RXRs. We conclude that
      retinoid may be a potential adjunctive chemotherapeutic agent for the treatment
      of canine MCT.

PMID- 16953079
TI  - Temporal and topographic profiles of tissue hypoxia following transient focal
      cerebral ischemia in rats.
AB  - Intravascular accumulation of blood cells after brain ischemia-reperfusion can
      cause obstruction of cerebral blood flow and tissue hypoxia/ischemia as a
      consequence. In the present study, we examined temporal and topographic changes
      of tissue hypoxia/ischemia after occlusion of the middle cerebral artery (MCA)
      for 60 min in rats with immunohistochemical staining for hypoxia (2
      nitroimidazole hypoxia marker: hypoxyprobe-1 adducts). Our results showed that
      tissue hypoxia expressed as positive staining for hypoxyprobe-1 adducts preceded
      neuronal degeneration. Platelets and granulocytes were detected close to the
      hypoxyprobe-1 adducts positive area. These results suggested that the hypoxic
      environment could persist even after reperfusion of MCA, because of vascular
      obstruction with accumulation of platelets and granulocytes.

PMID- 16953080
TI  - Efficient generation of canine bone marrow-derived dendritic cells.
AB  - Because of their unsurpassed potency in presenting antigens to naive T cells,
      dendritic cells are considered to be an important candidate in the development of
      immunotherapeutic strategies. Despite the high potential of dendritic cell-based
      immunotherapy, as a so-called dendritic cell vaccination, few clinical approaches
      using dendritic cell vaccination have been performed in the dog because of very
      limited information regarding the generation of canine dendritic cells and their
      functional properties. We therefore established a protocol for the efficient
      generation of dendritic cells from canine bone marrow cells using recombinant
      feline granulocyte-macrophage colony-stimulating factor and canine interleukin-4.
      Dendritic cells were generated efficiently: a yield of 1-9 x 10(6) cells per
      approximately 0.5 ml of canine bone marrow aspiration was achieved. These
      dendritic cells showed features shared with mouse and human dendritic cells:
      dendrite morphology, expression of surface markers MHC class II and CD11c, and up
      regulation of molecules related to antigen presentation (MHC class II, B7-1, and
      B7-2) by activation with lipopolysaccharide. Moreover, the dendritic cells
      demonstrated phagocytic activity, processing activity of pinocytosed proteins,
      and activation of allogeneic T cells far more potent than that by macrophages.
      Our findings suggest that the bone marrow-derived dendritic cells are functional
      for the capturing and processing of antigens and the initiation of T cell
      responses.

PMID- 16953081
TI  - PCR-based restriction fragment length polymorphism (RFLP) analysis of
      Campylobacter jejuni isolates from humans, chickens and dogs in northern Taiwan.
AB  - Two hundred and twenty strains of Campylobacter jejuni (70 human, 51 canine and
      99 chicken strains) were isolated from September 2003 to September 2004 in
      northern Taiwan. These strains were subtyped by PCR-RFLP analysis of the
      flagellin (FlaA) gene. On the basis of restrictive digest, six types were
      identified with AfaI, seven types with MboI and five types with HaeIII. With the
      combination of these three enzymes, 47 distinct PCR-RFLP patterns were observed
      25 each from human and chicken isolates, and 9 from canine isolates. In human
      strains, the most frequently occurring types were Cj-28 (14.3%), Cj-17 (10%), Cj
      16 (8.6%), Cj-37 (7.1%) and Cj-46 (7.1%). In canine strains, the most prevalent
      types were Cj-1 (33.3%), Cj-26 (19.6%), Cj-3 (15.7%), Cj-2 (9.8%) and Cj-10
      (9.8%). In chicken strains, the most frequently occurring types were Cj-46
      (40.4%), Cj-29 (9.1%), Cj-45 (7.1%) and Cj-41 (5.1%). The results suggest that
      poultry is a source, but not the sole source, of C. jejuni infection in humans.
      Two RFLP types, Cj-17 and Cj-37, frequently occurring in human isolates in this
      study have also been found to be prevalent in human isolates in Japan, China and
      the Czech Republic, indicating a possible international clonal spread.

PMID- 16953082
TI  - Preweaning mortality risks and recorded causes of death associated with
      production factors in swine breeding herds in Japan.
AB  - Preweaning mortality risks, recorded death reasons and related factors for
      preweaning mortality were studied in 105 breeding herds. Preweaning mortality
      risk at the herd level was calculated as the difference between the number of
      pigs born alive in farrowed litters and the number of weaned pigs divided by the
      number of pigs born alive in litters that farrowed and weaned. The mean of annual
      preweaning mortality risk was 10.7%. In regression analysis, higher mortality
      risks were associated with higher parity at farrowing, greater numbers of pigs
      born alive, and longer lactation length. The period from July to September had a
      higher mortality risk than that from April to June. The means of cause-specific
      proportional mortality ratios (PMR) in trauma with low viability and scours were
      80.4 and 6.2%, respectively. Sows with pig age 0-1 day during lactation had the
      highest daily PMR. Sows with pig age 0 to 7 days had higher PMR due to trauma and
      low variability than those with pig age 8 days older. Sows with pig age over 7
      days had higher PMR due to scours than those with pig age 0-7 days. Careful
      management at farrowing and in early lactation on high parity sows with large
      litters should be considered to prevent piglets from death due to trauma and low
      viability, and appropriate herd health programs should be implemented for
      reducing preweaning mortality due to scours during late lactation.

PMID- 16953083
TI  - Systolic blood pressure of clinically normal and conscious cats determined by an
      indirect Doppler method in a clinical setting.
AB  - The purposes of the present study were to determine the systolic blood pressure
      (SBP) of clinically normal and conscious cats, and to set up reference values of
      feline SBP for subsequent clinical application. SBPs were measured in 53 healthy
      cats using an ultrasonic Doppler device. The mean SBP was 133.6 +/- 16.0 mmHg
      (range, 110.0-180.0 mmHg). The distribution of SBP values was not significantly
      affected by factors such as breed, body condition score, or age (P>0.05), but SBP
      values of female cats were significantly lower and more variable than those of
      males (t test, P=0.004; F test, P<0.001). Feline SBP between 114.3 mmHg and 149.5
      mmHg was considered indicative of normotension. SBP values higher than 159.3 mmHg
      were defined as hypertension, and those less than 104.5 mmHg were determined as
      hypotension.

PMID- 16953084
TI  - Hepatozoonosis in two species of Japanese wild cat.
AB  - Hepatozoon sp. infections were detected in two species of Japanese wild cat,
      Iriomote wild cat (Felis iriomotensis) and Tsushima leopard cat (Felis
      bengalensis euptilura), between April 1993 and October 2005. The prevalence was
      56.7% (17/30) and 14.3% (6/42), respectively. The most affected organ was the
      heart; all infected animals had organisms in their hearts. The parasitizing form
      was schizont and various developmental stages were observed. The size of schizont
      and merozoite was 22.3 +/- 3.1 x 15.3 +/- 2.2 mum and 6.1 +/- 0.6 x 2.3 +/- 0.2
      mum, respectively. Few inflammatory reactions against the parasites were
      observed. Electron microscopically, organisms were located in parasitophorous
      vacuoles of unidentified host cells, and mature schizonts consisted of numerous
      merozoites. This is the first report of hepatozoonosis in Japanese felids.

PMID- 16953085
TI  - Chronic effect of transrectal split-focus ultrasonic ablation on canine prostatic
      tissue.
AB  - The treatment time needed for high-intensity focused ultrasound (HIFU) ablation
      might be decreased substantially by using the split-focus approach, so we made a
      prototype 4.2-MHz split-focus therapeutic transducer combined with a small 6.5
      MHz imaging ultrasonic probe for transrectally treatment of canine prostatic
      cancer and used it to experimentally evaluate the feasibility of using split
      focus transrectal HIFU to ablate canine prostatic tissue without injuring
      surrounding tissues. The prostates of 5 dogs were transrectally treated with
      split-focus ablation at a peak intensity in the water of 1.7 kW/cm(2) for 4 s (4
      shots) under the guidance of ultrasonic B-mode imaging. After ultrasonic
      exposure, the prostates became stiff because of thermal effect of HIFU. For the
      first 3-5 days after treatment, dogs were catheterized daily for urinary
      management and treated with oral antibiotics to prevent urinary tract infection.
      The dogs were able to urinate normally by a week after. Within two weeks a large
      centrally located cystic cavity had formed in the prostate by replacing the
      necrotic parenchyma around the prostatic urethra. Necropsy three months after
      treatment found the rectum and prostate capsule to be normal grossly and
      histologically. The 4 shots of split-focus HIFU destroyed the prostatic
      parenchyma and created a prostatic cavity 0.34-0.45 cm(3) in volume without
      injuring surrounding tissues. These results suggest that split-focus HIFU
      ablation could be used for noninvasive treatment of prostatic cancer in dogs.

PMID- 16953086
TI  - Characterization of the reproductive cycle in female bharals (Pseudois nayaur)
      based on the changes in serum progesterone concentrations and parturition season.
AB  - The purpose of present study was to determine annual changes in serum
      progesterone (P(4)) concentrations and to clarify basic reproductive
      characteristics, such as breeding season, estrous cycle, and puberty in female
      bharals (Pseudois nayaur). Blood was collected from 9 female bharals once or
      twice weekly for approximately one year. Serum P(4) concentrations were
      determined by radioimmunoassay. Serum P(4) concentrations showed remarkable and
      cyclic changes between November/December (winter) and May/June (late spring). The
      mean estrous cycle was 24.9 +/- 0.5 days. Chasing insistently to other females
      and discharge of mucus from the vulva were observed around the time when the
      serum P(4) concentrations began to increase. The chasing behavior and discharge
      of mucus were considered to be external indicators of estrus in female bharals.
      Serum P(4) concentrations of a pregnant female had non-cyclic changes, and the
      values remained high. In this study, all 37 deliveries were between April and
      September, and about 70% of these were concentrated in May and June. The
      conception month determined on the day of birth was between October and April for
      all animals, and the most common month was in December (54%). This month
      corresponded to an early stage of the period when the serum P(4) concentrations
      changed cyclically. These results indicate that many female bharals become
      pregnant at the beginning of the breeding seasons and, if they do not become
      pregnant, the estrous cycle, about 25 days in length, is repeated.

PMID- 16953087
TI  - Incidence of canine glaucoma with goniodysplasia in Japan : a retrospective
      study.
AB  - The incidence of primary and secondary glaucoma in dogs was investigated. A total
      of 1244 dogs received ophthalmologic examinations, including tonometry and
      gonioscopy. Goniophotographs were taken using a goniolens to evaluate the
      iridocorneal angle (ICA) as well as pectinate ligament (PL). The anterior width
      of the ciliary cleft and the total distance from the origin of the PL to the
      anterior corneal surface were measured from the goniophotographs. Glaucoma was
      diagnosed based on the cupping of the optic nerve head, clinical signs, ocular
      changes, and high IOP, and it was synchronized with gonioscopic grades to
      differentiate between primary and secondary glaucoma. We investigated 1244 dogs
      of 29 breeds, including the mixed breed; among these, glaucoma was diagnosed in
      127 dogs (162 eyes). Of 162 eyes, primary glaucoma was diagnosed in 129 eyes and
      secondary glaucoma in 33 eyes. Shiba Inu dogs (42 dogs, 33%) showed the highest
      incidence of glaucoma, followed by Shih-Tzu (21 dogs, 16.5%). Furthermore, all
      the glaucomatous Shiba Inu dogs had primary glaucoma with abnormal ICA grades and
      dysplastic PLs. The findings of our study reveal that the Shiba Inu breed in
      Japan may have a hereditary predisposition to glaucoma.

PMID- 16953088
TI  - Study on the porcinophilic foot-and-mouth disease virus I. production and
      characterization of monoclonal antibodies against VP1.
AB  - Monoclonal antibodies (MAbs) reported here were produced against the
      porcinophilic foot-and-mouth disease virus (FMDV) that caused the devastating
      swine disease on 1997 in Taiwan. A panel (25) of MAbs were found to react with
      VP1 of O/Taiwan/97 (O/97) by ELISA with various potencies. The biological
      identities of these VP1 reacting MAbs, such as neutralization activity, isotype
      and capability to distinguish between two serotype O FMDVs, O/97 and
      O/Taiwan/KM1/99 (O/99), were further analyzed. Eleven out of the total eighteen
      O/97 neutralizing MAbs were able to neutralize heterologous O/99. Eight O/97
      neutralizing and five non-neutralizing MAbs could differentiate two serotype O
      FMDVs by immunofluorescence assay (IFA) implied that these thirteen MAbs
      recognized O/97 specific epitope(s). Furthermore, reactivities of the VP1
      reacting MAbs with a 29 amino acids synthetic peptide (P29) representing the
      betaG-betaH loop of VP1 were analyzed by ELISA and fourteen were found positive.
      MAb clone Q10E-3 reacting strongest with VP1 and P29, neutralizing both but not
      differentiating two serotype O viruses suggested that the antibody binding site
      might involve the RGD motif and its C terminal conserved region on betaG-betaH
      loop. MAbs with diverse characters presented in this study were the first raised
      against porcinophilic FMDV. The complete set of MAbs may be used for further
      studies of vaccine, diagnostic methods, prophylaxis, etiological and
      immunological researches on FMDV.

PMID- 16953090
TI  - Erythema multiforme possibly triggered by food substances in a dog.
AB  - A 5-year-old female border collie presented with erythematous skin lesions at the
      axillae, groin, mucocutaneous junctions, and pinnae. Biopsy revealed lymphocytic
      interface dermatitis with hydropic degeneration of basal cells and keratinocyte
      apoptosis. Based on gross and histological features, diagnosis of erythema
      multiforme was made. The disease was resolved by treatment with azathioprine,
      prednisolone, and a hypoallergenic diet. Finally, the skin lesion was controlled
      without drug therapy but recurred easily every time commercial foods except the
      hypoallergenic diet were used, suggesting that food substances triggered this
      outbreak.

PMID- 16953089
TI  - Effects of olprinone on myocardial ischemia-reperfusion injury in dogs.
AB  - We investigated the effect of olprinone on canine myocardial pump function and
      myocardial damage after ischemia-reperfusion injury. Three dogs of the
      experimental group were given olprinone (Olprinone group) and another 3 dogs were
      served as control (Intact group). All animals were occluded left anterior
      descending artery for 60 min, followed by 6 hr of reperfusion. In the experiment,
      hemodynamics, infarct area, creatine kinase and troponin-I were measured.
      Olprinone infusion induced significantly high cardiac output value and
      significantly low values in left ventricular end diastolic pressure and systemic
      vascular resistance index after reperfusion. Also, olprinone tend to attenuate
      the infarct area, creatine kinase and troponin-I.

PMID- 16953091
TI  - Survey of coccidial oocysts and parasite eggs in feces of free-ranging Grus
      japonensis.
AB  - Fecal survey of Eimeria oocysts and parasite eggs was conducted for 219 fecal
      samples of free-ranging Grus japonensis in Kushiro district in Hokkaido in April
      2003. Positive rate and mean oocysts (or eggs) per gram in positive samples were
      26% (57/219) and 8.8 (0.2-136) in oocysts of Eimeria reichenowi, 18.3% (40/219)
      and 320 (100-1,000) in trematode eggs, 0.1% (2/219) and 0.2 (0.2-0.3) in eggs of
      Nematoda A, and 4.1% (9/219) and 0.8 (0.2-3.6) in eggs of Nematoda B,
      respectively.

PMID- 16953092
TI  - Comparison of tissue and fluid samples for the early detection of canine
      distemper virus in experimentally infected dogs.
AB  - The clinical utility of various specimens was examined for the early diagnosis of
      canine distemper (CD). Seven healthy dogs at 17 weeks of age were experimentally
      infected with a field isolate of canine distemper virus. The RT-PCR was carried
      out to detect CDV NP gene. Dogs showed mild fever and leukopenia, however,
      typical clinical signs of CD were not seen through the experimental period. CDV
      amplicons were detected more, earlier and for longer period in the conjunctival
      swabs than in the other samples employed. These results suggested that
      conjunctival swab samples, which are easy to obtain and non-invasive, would be
      the most suitable and practical specimen for the early antemortem diagnosis of
      CDV infection.

PMID- 16953093
TI  - Antimicrobial resistance in Salmonella isolates from apparently healthy food
      producing animal from 2000 to 2003: the first stage of Japanese veterinary
      antimicrobial resistance monitoring (JVARM).
AB  - Antimicrobial susceptibility of 183 Salmonella isolates from apparently healthy
      food-producing animals obtained during the period from 2000 to 2003 throughout
      Japan was examined. Of 29 serovars identified, Salmonella Infantis (37.7%) was
      the most prevalent, followed by S. Typhimurium (19.7%). Salmonella bacteria
      resistant to dihydrostreptomycin (77.6%) were about 10% more prevalent than those
      resistant to oxytetracycline (67.8%), though the nation-level veterinary use of
      tetracycline antibiotics is much greater than that of streptomycin in Japan. In
      seventeen isolates (9.3%) resistant to nalidixic acid, single point mutations
      were detected at 84 or 87 in the quinolone resistance-determining region of the
      gyrA gene.

PMID- 16953094
TI  - Molecular cloning of feline lung resistance-related protein (LRP) cDNA and its
      expression in a feline lymphoma cell line and adriamycin-resistant subline.
AB  - Molecular cloning of feline lung resistance-related protein (LRP) was performed
      to evaluate the relationship between its expression level and drug resistance
      against chemotherapeutics. The nucleotide sequence of the coding region of feline
      LRP cDNA was found to be 2670-bp long and to show 84.2-92.6% homology to its
      human, mouse, and rat counterparts. The expression level of feline LRP mRNA was
      relatively high in lung, jejunum, and colon. An adriamycin (ADM)-resistant feline
      lymphoma subline, FT-1/ADM, showed a high level of MDR1 mRNA expression compared
      with parental FT-1 cells. However, no relationship was observed between the drug
      resistant phenotype and the LRP mRNA expression level. Although no direct
      contribution of LRP to the development of the drug-resistant phenotype was
      observed, further investigation is advisable.

PMID- 16953095
TI  - Nephroblastoma with transcoelomic metastasis in a Japanese black bull.
AB  - This paper describes a nephroblastoma with transcoelomic metastasis in a three
      year-old Japanese black bull. At necropsy, a huge, oval neoplastic mass
      containing the residual right kidney was found. Moreover, severe transcoelomic
      metastasis occurred throughout the abdominal and thoracic cavities.
      Histologically, the mass was mainly composed of sheets, nests, islands and cords
      of polygonal blastemal cells with trabeculae of fibrous stroma. In some areas,
      epithelial elements composed of tubules and winding duct-like structures were
      also observed. Glomeruloid structures were scattered in these epithelial
      elements. Metastatic nodules were composed of blastemal and stromal elements,
      which were similar to those in the mass.

PMID- 16953096
TI  - Primary hemangiosarcoma of the humerus in a Maltese dog.
AB  - A 14-year-old intact male Maltese dog was presented with a history of pain and
      swelling of the left upper forelimb and lameness for 3 weeks. Hematological and
      radiographical examinations showed regenerative anemia and osteolysis of the
      humerus. Fine needle aspiration biopsy detected epithelioid- and fibroblast-like
      anaplastic cells with blood components. A hemorrhagic and osteolytic malignant
      tumor was suspected, and the affected forelimb was amputated.
      Histopathologically, the dog was diagnosed with primary hemangiosarcoma of the
      humerus. Thereafter, metastatic lesions appeared in the skin, and the dog was
      euthanized 1 month after the operation.

PMID- 16953097
TI  - Suppressive effect of hyaluronan on chondrocyte apoptosis in experimentally
      induced acute osteoarthritis in dogs.
AB  - Dogs receiving anterior cruciate ligament transection (ACLT) were treated with
      either intravenous (IV) or intraarticular (IA) administration of hyaluronan (HA),
      and differences in appearance of chondrocyte apoptosis of the stifle joint were
      investigated. Chondrocyte apoptosis was detected using flow cytometry as well as
      by staining with TdT-mediated dUTP nick end labeling (TUNEL). The percentage of
      apoptotic chondrocytes in dogs with ACLT was significantly higher than that in
      intact (non-ACLT) dogs. Dogs treated with IA or IV injection of HA after ACLT had
      fewer apoptotic chondrocytes than non-treated dogs after ACLT. It was suggested
      that ACLT-induced apoptosis of chondrocytes was suppressed by HA administration
      of either IA or IV.

PMID- 16953098
TI  - [Earlier detection of ulcerative colitis-associated cancer: the present and
      future of surveillance].

PMID- 16953099
TI  - [Pathophysiology of functional dyspepsia].

PMID- 16953100
TI  - [A case of Turner syndrome complicated with Crohn's disease, erythema nodosum and
      Hashimoto disease].
AB  - A 26-year-old woman, who had had Turner syndrome from age 10 years old, had
      diarrhea, fever, joint pain, and erythema in the lower left leg. She was given a
      diagnosis of Crohn's disease, erythema nodosum, and Hashimoto disease. Systemic
      steroid therapy was very effective for both intestinal and skin lesions. It has
      been reported that half of inflammatory bowel disease patients with Turner
      syndrome have 46XiX (q) type chromosome abnormality, and this case also has this
      type of abnormality.

PMID- 16953101
TI  - [A case report: Severe bone marrow suppression caused by 6-mercaptopurin in
      Crohn's disease patient].
AB  - A 23-year-old man was admitted for treatment of acute exacerbation of ileitis and
      perianal abscess caused by Crohn's disease. After incision and drainage of the
      abscess, coupled with antibiotic therapy, 6-mercaptopurine (6-MP) was commenced.
      His white blood cell (WBC) count on day 12 after initiation of 6-MP was not
      decreased. However, on day 24 he was re-admitted because of severe
      myelosuppression (WBC: 300/microl), which was complicated by the recurrence of
      the perianal abscess. Myelosuppression was prolonged and required the
      administration of granulocyte colony stimulating factor (G-CSF). G-CSF was
      continued for 17 days to achieve recovery of his WBC count to a normal level.

PMID- 16953102
TI  - [A case of hepatosplenic cat scratch disease].
AB  - A 43-year-old man was admitted with idiopathic fever. Abdominal ultrasonogram
      demonstrated multiple hypoechoic lesions in the spleen. Abdominal CT scan showed
      multiple hypodense lesions in the liver and spleen. The patient had a cat in his
      house, and the presence of a very high serous antibody titer for Bartonella
      henselae led to the diagnosis of hepatosplenic cat scratch disease. It is
      important to consider this disease in the differential diagnosis of idiopathic
      fever when multiple lesions are detected in the liver and spleen.

PMID- 16953103
TI  - [Manifestation of liver metastasis 13 years after gastrectomy for gastric GIST].
AB  - A 58-year-old Japanese man underwent partial gastrectomy in 1991 for a tumor
      showing extra-gastric growth measuring 18 x 16.5 x 8.8 cm in size. An
      immunohistochemical study yielded a diagnosis of gastric GIST with few mitoses.
      In 2004, abdominal CT showed a solitary liver metastasis without extrahepatic
      recurrence and right hepatic lobectomy was performed. No adjuvant treatment has
      been done and he is alive without recurrence 1 year after the hepatectomy. Long
      term follow-up of more than 10 years is required after resection of primary
      tumors if they are diagnosed as high risk GISTs with few mitoses.

PMID- 16953104
TI  - [A case of exacerbation of ulcerative colitis induced by combination therapy with
      PEG-interferon alpha-2b and ribavirin for chronic hepatitis C].
AB  - A 55-year-old man with chronic hepatitis C had diarrhea with bloody stool in
      July, 2003 and ulcerative colitis was suspected. However, he quickly improved. He
      was treated with percutaneous radiofrequency ablation therapy for adenomatous
      hyperplasia in S5 of the liver in December, 2004. After the ablation therapy, he
      was treated with combination therapy of PEG-interferon alpha-2b and ribavirin for
      chronic hepatitis C. Because exacerbation of ulcerative colitis appeared 10 weeks
      after beginning of the treatment for hepatitis C, the combination therapy of PEG
      interferon and ribavirin was discontinued. He was treated with mesalazine and
      steroid therapy for ulcerative colitis, and improved. We report the first case in
      Japan of the exacerbation of ulcerative colitis induced by the combination
      therapy of PEG-interferon and ribavirin for chronic hepatitis C.

PMID- 16953105
TI  - [A case of extrahepatic portal vein aneurysm with the remarkably bent bile duct
      by its displacement].
AB  - A 50-year-old man with type B liver cirrohosis was admitted with jaundice and
      ascites. He had undergone an operation for esophageal variceal rupture at another
      hospital. Abdominal CT scan and ultrasonography showed cystic dilatation of the
      extrahepatic portal vein, and Doppler ultrasonography showed it to be a portal
      vein aneurysm. After admission, jaundice progressed, and not only liver failure
      but also biliary tract obstruction was suspected as its etiology. Therefore,
      endoscopic retrograde cholangiography was performed, and it showed a remarkably
      bent extrahepatic bile duct thought to be caused by extrinsic compression. By
      combining the finding of endoscopic ultrasonography, we considered that the
      portal vein aneurysm had displaced the bile duct. We suspected that it also
      caused cholestasis and cholangitis.

PMID- 16953106
TI  - Effects of post-treatment with direct hemoperfusion using a CTR column on
      mortality and inflammatory responses to endotoxin-induced shock in rats.
AB  - BACKGROUND: To clarify the effects of post-treatment with direct hemoperfusion
      using a CTR column on the mortality and inflammatory responses to endotoxin
      induced shock in rats. METHODS: Thirty-six male rats were randomly assigned to 1
      of 3 groups (n = 12/group): the endotoxemic group, receiving intravenous
      Escherichia coli endotoxin (15 mg/kg over 2 min); the control column group,
      treated without CTR for 120 min at 2 h after endotoxin injection, and CTR-post
      treatment group, treated with CTR for 120 min at 2 h after endotoxin injection.
      Hemodynamics, arterial blood gases, and mortality were recorded for the 8-hour
      observation period, and plasma cytokine concentrations were measured every 4 h.
      RESULTS: The mortality rates were 83, 83 and 33% for the endotoxemic, control
      column, and CTR post-treatment groups, respectively. The increases in IL-6
      concentrations were less for the CTR post-treatment group than the other 2
      groups. CONCLUSION: The present study shows that CTR post-treatment inhibited
      hypotension and elevations in IL-6 concentrations, reducing the mortality rate of
      rats with endotoxin-induced shock.

PMID- 16953107
TI  - Characteristics and outcome of acute myocardial infarction in young patients. The
      PRIAMHO II study.
AB  - BACKGROUND: The objective was to analyze the incidence, risk factors, management,
      and complications of acute myocardial infarction (AMI) in the young patient in
      Spain. METHODS: Clinical characteristics, treatment, and outcome were analyzed in
      patients younger than 45 years admitted with an AMI diagnosis to the Coronary
      Units of 58 Spanish hospitals from 15th May to 15th December 2000. RESULTS: Six
      thousand two hundred and ten consecutive patients were registered, 7% out of them
      were <45 years old. Outcome was better in the younger group, with a lower
      mortality rate at 28 days (3.7 vs. 11.9%; p < 0.001), demonstrating that age <45
      years is an independent protective factor for mortality (relative risk: 0.41; 95%
      CI: 0.23-0.73; p < 0.001). This difference remained at 1-year follow-up.
      CONCLUSIONS: AMI in young patients presents distinct clinical characteristics, a
      different treatment, management and outcome with respect to the older group.

PMID- 16953108
TI  - Aortic pulse pressure and aortic pulsatility in patients with coronary slow flow.
AB  - OBJECTIVE: Coronary slow flow (CSF) is an angiographic phenomenon characterized
      by delayed opacification of coronary arteries in the absence of obstructive
      coronary disease. Recently, increased aortic pulse pressure (PP) and aortic
      pulsatility were both linked to the presence of angiographic coronary artery
      disease. In this study aortic PP and aortic pulsatility, derived from the
      invasively measured ascending aortic pressure waveform, were analyzed in patients
      with CSF and otherwise normal epicardial coronary arteries and compared with
      those with completely normal coronary arteries. METHODS: Fifty consecutive
      patients with CSF (35 men, mean age: 51.7 +/- 10 years) and fifty age and gender
      matched controls (34 men, 51.1 +/- 9 years) were included in the study. For
      determination of coronary flow, the thrombosis in myocardial infarction (TIMI)
      frame count method was used. Blood pressure waveforms of the ascending aorta were
      measured during cardiac catheterization with a fluid-filled system. Aortic
      pulsatility was estimated as the ratio of aortic PP to mean pressure. RESULTS:
      Study groups were well matched with respect to age, gender and atherosclerotic
      risk factors. Although systolic, diastolic and mean pressures of the ascending
      aorta were similar, aortic PP (60.5 +/- 19 vs. 51.7 +/- 14 mm Hg, p = 0.01) and
      aortic pulsatility (0.63 +/- 0.1 vs. 0.54 +/- 0.1, p = 0.006) were significantly
      higher in patients with CSF compared with the controls. Besides, in all subjects,
      corrected TIMI frame counts of all three coronary arteries correlated with both
      ascending aorta PP and aortic pulsatility values. No association was found
      between corrected TIMI frame counts of coronary arteries and aortic mean blood
      pressure or brachial blood pressure parameters. CONCLUSION: Our findings suggest
      that CSF is, as with obstructive coronary artery disease, associated with more
      diffuse vascular disease rather than being an isolated finding.

PMID- 16953109
TI  - Chronic development of ischaemic mitral regurgitation during post-infarction
      remodelling.
AB  - BACKGROUND/AIMS: Mitral regurgitation (MR) following myocardial infarction (MI)
      may be a (sub)acute complication which independently predicts reduced survival.
      We sought to evaluate the chronic development of MR as potential consequence of
      left-ventricular (LV) remodelling, the latter being a long-term process. METHODS
      AND RESULTS: Retrospectively, 103 post-MI patients were included according to a
      standardised Doppler echocardiogram <3 months following MI (20 +/- 25 days post
      MI) and a follow-up examination >6 months after the first examination (5.1 +/-
      3.1 years post-MI). Patients were clinically followed up for 7.6 +/- 2.7 years.
      Group I patients were defined as those showing new development or deterioration
      in one of three grades of MR, and group II those without this criterion (MR grade
      acute 0.17 vs. 0.27, p = 0.7, and chronic 1.53 vs. 0.19, p < 0.0001). Patient
      characteristics were similar in respect of age, gender, size and location of
      infarction. However, group I patients had coronary artery disease with more
      vessels involved. With regard to echocardiographic parameters of significantly
      enlarged LV chamber size in group I vs. group II, the significant decrease in LV
      performance was more pronounced and occurred concomitant with a higher degree of
      symptomatic congestive heart failure and greater need for heart failure
      medications in group I. Mortality in group I patients was 39 versus 9% in group
      II patients (p = 0.0002), approximating an odds ratio of 6.4697 (95% confidence
      interval: 2.211-18.931). CONCLUSION: First of all, this retrospective study
      indicates that MR may be detected in patients after MI during a long-term follow
      up most probably due to geometric distortions of LV remodelling resulting in a
      significantly higher mortality. Since this process is known to become
      irreversible at a certain point, serial echocardiography may help to detect MR in
      post-MI patients and thus pave the way for appropriate treatment.

PMID- 16953110
TI  - Fibrosis of collagen I and remodeling of connexin 43 in atrial myocardium of
      patients with atrial fibrillation.
AB  - BACKGROUND: Fibrosis in atrial myocardium is a common phenomenon for patients
      with atrial fibrillation (AF). Remodeling of connexins was found accompanying
      with AF. The aim of the study is to investigate whether it is by causing the
      remodeling of connexin 43 (Cx43) that the fibrosis of atrial muscle plays an
      important role during the initiation and maintenance of AF. METHODS: Samples of
      right atrial appendage were taken from 24 patients with rheumatic valvular
      disease during surgery. Fibrosis and remodeling of Cx43 was examined by
      microscopy and ultramicroscopy technique and analyzed by image analyzer. The
      collagen volume fraction of type I (CVF-I) and the volume fraction of Cx43
      (Cx43VF) were studied between AF and sinus rhythm (SR) groups. RESULTS: (1)
      Microscopic examination demonstrated that CVF-I significantly increased and
      Cx43VF decreased in patients with AF compared to those with SR. (2) The CVF-I was
      negatively correlated with the Cx43VF. CONCLUSION: The results suggest that
      fibrosis and remodeling of Cx43 are involved in the pathophysiologic mechanism of
      human AF. Fibrosis of atrial muscle may play an important role in the process of
      AF by means of interfering with remodeling of connexins.

PMID- 16953111
TI  - In vitro evaluation of metallic coronary artery stents with sub-millimeter multi
      slice computed tomography using an ECG-gated cardiac phantom: relationship
      between in-stent visualization and stent type.
AB  - The aim of this experimental study was to investigate visualization of various
      coronary artery stents with sub-millimeter multi-slice spiral computed tomography
      (MSCT) using a cardiac physical phantom. Four 3-mm stents of various designs were
      implanted in tubes with an inner diameter of 3 mm to simulate coronary artery.
      Stents were placed on a cardiac phantom and scanned at different heart rates.
      Retrospective ECG-gated adaptive segmental reconstruction technique was employed.
      Profile curves across longitudinal curved planar reconstruction images of the
      stents were generated. From the profile curve, the full width at half maximum was
      defined as the stent lumen index. The effect of heart rate and stent type on the
      stent lumen index was evaluated. Visual evaluation for each stent at various
      heart rates was also performed. The heart rate had no significant effect on in
      stent visualization. However, in-stent visualization differed significantly for
      the various stent types for both profile curve analysis and visual evaluation
      (the Tukey-Kramer multiple comparisons test). Multiple regression analysis
      indicated that strut thickness, especially minimal strut thickness, was the
      significant influencing factor for the in-stent visualization. On the basis of
      four stent models examined it would appear that visualization of the coronary
      stent lumen varies depending on the stent type, but not on the heart rate. Stents
      with slim struts are preferable for in-stent evaluation with multi-slice spiral
      computed tomography.

PMID- 16953112
TI  - Microglia, major player in the brain inflammation: their roles in the
      pathogenesis of Parkinson's disease.
AB  - Inflammation, a self-defensive reaction against various pathogenic stimuli, may
      become harmful self-damaging process. Increasing evidence has linked chronic
      inflammation to a number of neurodegenerative disorders including Alzheimer's
      disease (AD), Parkinson's disease (PD), and multiple sclerosis. In the central
      nervous system, microglia, the resident innate immune cells play major role in
      the inflammatory process. Although they form the first line of defense for the
      neural parenchyma, uncontrolled activation of microglia may directly toxic to
      neurons by releasing various substances such as inflammatory cytokines (IL-1beta,
      TNF-alpha, IL-6), NO, PGE(2), and superoxide. Moreover, our recent study
      demonstrated that activated microglia phagocytose not only damaged cell debris
      but also neighboring intact cells. It further supports their active participation
      in self-perpetuating neuronal damaging cycles. In the following review, we
      discuss microglial responses to damaging neurons, known activators released from
      injured neurons and how microglia cause neuronal degeneration. In the last part,
      microglial activation and their role in PD are discussed in depth.

PMID- 16953113
TI  - Downregulation of neurotrophic factors in the brain of a mouse model of Gaucher
      disease; implications for neuronal loss in Gaucher disease.
AB  - Gaucher disease is a glycosphingolipid storage disease caused by deficiency of
      glucocerebrosidase, resulting in the accumulation of glucosylceramide in
      lysosomes. The neuronopathic forms of this disease are associated with neuronal
      loss and neurodegeneration. However, the pathophysiological mechanisms leading to
      prenatal and neonatal death remain uncharacterized. To investigate brain
      dysfunction in Gaucher disease, we studied the effects of neurotrophic factors
      during development in a mouse model of Gaucher disease. The expression of brain
      derived neurotrophic factor and nerve growth factor was reduced in the cerebral
      cortex, brainstem, and cerebellum of Gaucher mice, compared with that in wild
      type mice. Extracellular signal-regulated kinase (ERK) 1/2 expression was
      downregulated in neurons from Gaucher mice and correlated with a decreased number
      of neurons. These results suggest that a reduction in neurotrophic factors could
      be involved in neuronal loss in Gaucher disease.

PMID- 16953114
TI  - CD43 cross-linking increases the Fas-induced apoptosis through induction of Fas
      aggregation in Jurkat T-cells.
AB  - CD43 (sialophorin, leukosialin) is a heavily sialylated surface protein expressed
      on most leukocytes and platelets including T cells. Although CD43 antigen is
      known to have multiple and complex structure, exact function of CD43 in each cell
      type is not completely understood. Here we evaluated the role of CD43 in Fas
      (CD95)-induced cell death in human T lymphoblastoid cell line, Jurkat.
      Crosslinking CD43 antigen by K06 mAb increased the Fas-mediated Jurkat cell
      apoptosis and the augmentation was inhibited by treatment with caspase
      inhibitors. Further, CD43 signaling of Jurkat cells induced Fas oligomerization
      on the cell surfaces implying that CD43 ligation have effects on early stage of
      Fas-induced T cell death. These also suggest that CD43 might play an important
      role in contraction of the immune response by promotion of Fas-induced apoptosis
      in human T cells.

PMID- 16953115
TI  - Release of heat shock protein 70 (Hsp70) and the effects of extracellular Hsp70
      on matric metalloproteinase-9 expression in human monocytic U937 cells.
AB  - Heat shock protein 70 (Hsp70) release and its effects on pro-inflammatory
      cytokine production have been controversial. In this study, we investigated
      whether Hsp70 could be released from monocytes and activates matrix
      metalloproteinase-9 (MMP-9) gene expression. Hsp70 overexpression in human
      monocytic cell line U937 was found to increase PMA-induced MMP-9 expression and
      enhance cell motility. Hsp70 cDNA transfectants released Hsp70 protein into
      culture supernatants, and a part of released Hsp70 subsequently was bound to the
      surface of U937 cells. Addition of culture medium containing the extracelluar
      Hsp70 led to an increase not only in proMMP-9 secretion, but also the
      invasiveness of U937 cells through Matrigel or human umbilical vascular
      endothelial cells (HUVEC) in vitro. Immunodepletion of Hsp70 abolished its effect
      on MMP-9 expression. The released Hsp70 activated nuclear factor kappa B (NF
      kappaB) and activating protein-1 (AP-1), which led to the activation of MMP-9
      transcription. Taken together, these results suggest that extracellular Hsp70
      induces the expression of MMP-9 gene through activation of NF-KappaB and AP-1.

PMID- 16953116
TI  - Lysophosphatidylcholine suppresses apoptosis and induces neurite outgrowth in
      PC12 cells through activation of phospholipase D2.
AB  - Lysophosphatidylcholine (LPC) is a bioactive lipid generated by phospholipase A2
      mediated hydrolysis of phosphatidylcholine. In the present study, we demonstrate
      that LPC stimulates phospholipase D2 (PLD2) activity in rat pheochromocytoma PC12
      cells. Serum deprivation induced cell death of PC12 cells, as demonstrated by
      decreased viability, DNA fragmentation, and increased sub-G1 fraction of cell
      cycle. LPC treatment protected PC12 cells partially from the cell death and
      induced neurite outgrowth of the cells. Overexpression of PLD2 drastically
      enhanced the LPC-induced inhibition of apoptosis and neuritogenesis. Pretreatment
      of the cells with 1-butanol, a PLD inhibitor, completely abrogated the LPC
      induced inhibition of apoptosis and neurite outgrowth in PC12 cells
      overexpressing PLD2. These results indicate that LPC possesses the neurotrophic
      effects, such as anti-apoptosis and neurite outgrowth, through activation of
      PLD2.

PMID- 16953117
TI  - Development of ligand-dependent regulatory system and its application to gene
      therapy of insulin-dependent diabetes mellitus.
AB  - To develop an inducible expression system, the enhanced artificial nuclear
      receptors and target reporters were constructed. Artificial nuclear receptors
      were generated by fusing three domains, consisting of DNA-binding domain (DBD) of
      GAL4, ligand binding domain (LBD) of progesterone or estrogen receptor, and
      activation domain (AD) of VP16, sterol regulatory element binding protein (SREBP)
      1a, or SREBP-2. The activation domain of SREBP-1a showed most potent
      transcriptional activity. The maximal level of target reporter gene expression
      was extremely elevated by the usage of ATP citrate-lyase (ACL) minimal promoter 
      60/+67 in place of artificial TATA promoter, while the SV40 enhancer severely
      increased the basal transcription in the absence of ligand. The induction system,
      developed in the present study, was applied to cell therapy, resulting in
      successful induction of single-chain insulin analogue (SIA) gene expression to
      correct the hyperglycemia in diabetic animals. By means of subcutaneous cell
      therapy, the SIA gene expression rapidly occurred after the local topical
      application of ligand. These results suggest that our system represents a
      powerful tool for transcriptional regulation of target gene that can be used for
      diverse applications, ranging from basic research to gene therapy.

PMID- 16953118
TI  - Comparative effects of curcuminoids on endothelial heme oxygenase-1 expression:
      ortho-methoxy groups are essential to enhance heme oxygenase activity and
      protection.
AB  - Recently, it has been reported that curcumin, which is known as a potent
      antioxidant, acts as a non- stressful and non-cytotoxic inducer of the
      cytoprotective heme oxygenase (HO)-1. In this study, naturally occurring
      curcuminoids, such as pure curcumin, demethoxycurcumin (DMC) and bis
      demethoxycurcumin (BDMC), were compared for their potential ability to modulate
      HO-1 expression and cytoprotective activity in human endothelial cells. All three
      curcuminoids could induce HO-1 expression and HO activity with differential
      levels. The rank order of HO activity was curcumin, DMC and BDMC. In comparison
      with endothelial protection against H2O2-induced cellular injury, cytoprotective
      capacity was found to be highest with curcumin, followed by DMC and BDMC.
      Interestingly, cytoprotective effects afforded by curcuminoids were considerably
      associated with their abilities to enhance HO activity. Considering that the main
      difference among the three curcuminoids is the number of methoxy groups (none for
      BDMC, one for DMC, and two for curcumin), the presence of methoxy groups in the
      ortho position on the aromatic ring was suggested to be essential to enhance HO-1
      expression and cytoprotection in human endothelial cells. Our results may be
      useful in designing more efficacious HO-1 inducers which could be considered as
      promising pharmacological agents in the development of therapeutic approaches for
      the prevention or treatment of endothelial diseases caused by oxidative damages.

PMID- 16953119
TI  - Metabolic loading of guanosine induces chondrocyte apoptosis via the Fas pathway.
AB  - Although the apoptosis of chondrocytes plays an important role in endochondral
      ossification, its mechanism has not been elucidated. In this study, we show that
      guanosine induces chondrocyte apoptosis based on the results of acridine
      orange/ethidium bromide staining, caspase-3 activation, and sub-G1 fraction
      analysis. The potent inhibitory effect of dipyridamole, a nucleoside transporter
      blocker, indicates that extracellular guanosine must enter the chondrocytes to
      induce apoptosis. We found that guanosine promotes Fas-Fas ligand interaction
      which, in turn, leads to chondrocyte apoptosis. These findings indicate a novel
      mechanism for endochondral ossification via metabolic regulation.

PMID- 16953120
TI  - SP600125, a selective JNK inhibitor, aggravates hepatic ischemia-reperfusion
      injury.
AB  - c-Jun N-terminal kinase (JNK) is activated during hepatic reperfusion, and JNK
      inhibitors are known to protect other major organs from ischemia-reperfusion
      (I/R) injury. We attempted to determine the effect of SP600125, a JNK inhibitor,
      on hepatic I/R injury using a partial ischemia model in mice. Compared to a
      vehicle-treated group, the SP600125- treated group showed a greater increase in
      serum ALT levels 24 h after reperfusion with more severe parenchymal destruction
      and leukocyte infiltration. Similarly, tissue myeloperoxidase and malondialdehyde
      levels were higher in the SP600125-treated group, and chemokine expression was
      also higher in the SP600125-treated group. These data, which are contradictory to
      previous results, indicate that JNK inhibition by SP600125 may be harmful in
      hepatic I/R injury. Therefore, care must be taken when investigating the
      therapeutic use of JNK inhibitors in hepatic I/R injury, especially in the
      context of the effects of JNK inhibition on inflammatory infiltration.

PMID- 16953122
TI  - Involvement of JNK-initiated p53 accumulation and phosphorylation of p53 in
      pseudolaric acid B induced cell death.
AB  - A terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)
      assay was used to determine that apoptosis causes HeLa cell death induced by
      pseudolaric acid B. The c-Jun N-terminal kinase (JNK) inhibitor SP600125
      decreased p53 protein expression during exposure to pseudolaric acid B. SP600125
      decreased the phosphorylation of p53 during pseudolaric acid B exposure,
      indicating that JNK mediates phosphorylation of p53 during the response to
      pseudolaric acid B. SP600125 reversed pseudolaric acid B-induced down-regulation
      of phosphorylated extracellular signal-regulated protein kinase (ERK), and
      protein kinase C (PKC) was activated by pseudolaric acid B, whereas
      staurosporine, calphostin C, and H7 partly blocked this effect. These results
      indicate that p53 is partially regulated by JNK in pseudolaric acid B-induced
      HeLa cell death and that PKC participates in pseudolaric acid B-induced HeLa cell
      death.

PMID- 16953121
TI  - Anti-inflammatory effects of 8-hydroxydeoxyguanosine in LPS-induced microglia
      activation: suppression of STAT3-mediated intercellular adhesion molecule-1
      expression.
AB  - To elucidate the roles of 8-hydroxydeoxyguanosine (oh(8)dG), the nucleoside of 8
      hydroxyguanine (oh(8)Gua), we examined the effects of oh(8)dG upon LPS-induced
      intercellular adhesion molecule-1 (ICAM-1) expression and the underlying
      mechanisms in brain microglial cells. We found that oh(8)dG reduces LPS-induced
      reactive oxygen species (ROS) production, STAT3 activation, and ICAM-1
      expression. oh(8)dG also suppresses pro-inflammatory cytokines, such as TNF
      alpha, IL-6 and IFN-gamma. Overexpression of dominant negative STAT3 completely
      diminshed STAT3-mediated ICAM-1 transcriptional activity. Chromatin
      immunoprecipitation studies revealed that oh(8)dG inhibited recruitment of STAT3
      to the ICAM-1 promoter, followed by a decrease in ICAM-1 expression. Using mice
      lacking a functional Toll-like receptor 4 (TLR4), we demonstrated that, while
      TLR4+/+ microglia were activated by LPS, TLR4-/- microglia exhibited inactivated
      STAT3 in response to LPS. Evidently, LPS modulates STAT3-dependent ICAM-1
      induction through TLR4-mdiated cellular responses. Oh(8)dG apparently plays a
      role in anti-inflammatory actions via suppression of ICAM-1 gene expression by
      blockade of the TLR4-STAT3 signal cascade in inflammation-enhanced brain
      microglia. Therefore, oh(8)dG in the cytosol probably functions as an anti
      inflammatory molecule and should be considered as a candidate for development of
      anti-inflammatory agents.

PMID- 16953123
TI  - Up-regulation of Bax and endonuclease G, and down-modulation of Bcl-XL involved
      in cardiotoxin III-induced apoptosis in K562 cells.
AB  - Cardiotoxin III (CTX III), a basic polypeptide with 60 amino acid residues
      isolated from Naja naja atra venom, has been reported to have anticancer
      activity. CTX III-induced K562 cell apoptosis was confirmed by DNA fragmentation
      (DNA ladder, sub-G1 formation) and phosphatidylserine (PS) externalization with
      an IC(50) value of 1.7 microg/ml at 48 h. A mechanistic analysis demonstrated
      that CTX III-induced apoptotic cell death was accompanied by up-regulation of
      both Bax and endonuclease G (Endo G), and downregulation of Bcl-X(L). CTX III had
      no effect on the levels of Bcl-2, Bid, XIAP survivin, and AIF proteins. CTX III
      treatment caused loss of the mitochondrial membrane potential (DeltaPsim),
      release of mitochondrial cytochrome c to the cytosol, and activation of both
      caspase-9 and -3. CTX III-induced apoptosis was significantly blocked by the
      broad-spectrum caspase inhibitor Z-VAD-FMK. However, CTX III did not generate
      reactive oxygen species (ROS) and antioxidants, including N-acetylcysteine and
      catalase, did not block CTX III-induced apoptosis in K562 cells. Modulation of
      Bax, Bcl-XL, and the Endo G proteins, release of mitochondrial cytochome c, and
      activation of caspase-3 and -9 all are involved in the CTX III-triggered
      apoptotic process in human leukemia K562 cells.

PMID- 16953124
TI  - Inhibitory effects of tilianin on the expression of inducible nitric oxide
      synthase in low density lipoprotein receptor deficiency mice.
AB  - We investigated the effect of tilianin upon inducible nitric oxide synthesis in
      the plasma of low-density lipoprotein receptor knock-out (Ldlr-/-) mice fed with
      high cholesterol diet and in primary peritoneal macrophages of Ldlr-/- mice. High
      cholesterol diet induced nitric oxide production in the plasma of Ldlr-/- mice.
      Tilianin reduced the level of nitric oxide (NO) in plasma from Ldlr-/- mice
      induced by the high cholesterol diet. Tilianin also inhibited the NO production
      from the primary culture of peritoneal macrophages treated with
      lipopolysaccharide. The inhibition of NO production was caused by the suppression
      of inducible nitric oxide synthase (iNOS) gene expression in peritoneal
      macrophages isolated from Ldlr-/- mice. Moreover, tilianin inhibited the
      transcriptional activation of iNOS promoter that has NF-kappaB binding element.
      Thus, these results provide the first evidence that tilianin inhibit iNOS
      expression and production of NO and may act as a potential anti-inflammatory
      agent.

PMID- 16953125
TI  - [The effect of assertiveness training on communication related factors and
      personnel turnover rate among hospital nurses].
AB  - PURPOSE: The purpose of this study was to investigate the effects of
      assertiveness training on nurses' assertive behaviors, interpersonal relations,
      communication conflicts, conflict management style and personnel turnover rate.
      METHOD: A non-equivalent control group pretest-posttest design was used in this
      study. Nurses were assigned into the experimental or control groups, each
      consisting of 39 nurses. Data was collected between January to March 2004. An
      'Assertiveness Training Program' for Nurses developed by Park was used for the
      study. To emphasize assertiveness practice, 5 practice sessions utilizing ABCDE
      principles were added to Park's program. To examine the effects of the program,
      differences between the two groups in assertive behaviors, interpersonal
      relations, communication conflicts, conflict management style and personnel
      turnover rate were analyzed using ANCOVA. RESULTS: The assertiveness training was
      effective in improving the nurses' assertiveness behaviors, but was not effective
      in improving interpersonal relations, reducing the subjects' communication
      conflicts, changing the conflict management style or reducing their personnel
      turnover rate. CONCLUSION: There have been many studies about factors affecting
      nurses' personnel turnover rates, but few have been done about methods of
      intervention to reduce the personnel turnover rate. Thus, this study provides a
      significant contribution in attempting such an intervention from nursing
      management perspectives.

PMID- 16953126
TI  - [Variations in nurse staffing in adult and neonatal intensive care units].
AB  - PURPOSE: This study was done to analyze variations in unit staffing and recommend
      policies to improve nursing staffing levels in intensive care units (ICUs).
      METHOD: A cross-sectional study design was used, employing survey data from the
      Health Insurance Review Agency conducted from June-July, 2003. Unitstaffing was
      measured using two indicators; bed-to-nurse (B/N) ratio (number of beds per
      nurse), and patient-to-nurse (P/N)ratio (number of average daily patients per
      nurse). Staffing levels were compared according to hospital and ICU
      characteristics. RESULT: A total of 414 institutions were operating 569 adult and
      86 neonatal ICUs. Tertiary hospitals (n=42) had the lowest mean B/N (0.82) and
      P/N (0.76) ratios in adult ICUs, followed by general hospitals (B/N: 1.34, P/N:
      0.97). Those ratios indicated that a nurse took care of 3 to 5 patients per
      shift. Neonatal ICUs had worse staffing and had greater variations in staffing
      ratios than adult ICUs. About 17% of adult and 26% of neonatal ICUs were staffed
      only by adjunct nurses who had responsibility for a general ward as well as the
      ICU. CONCLUSION: Stratification of nurse staffing levels and differentiation of
      ICU utilization fees based on staffing grades are recommended as a policy tool to
      improve nurse staffing in ICUs.

PMID- 16953127
TI  - [Effects of Logotherapy with Exercise on meaning of life, ego integrity and IADL
      in the elderly].
AB  - PURPOSE: The purpose of this study was to examine the effects of 'Logotherapy
      with Exercise' on the meaning of life, ego integrity and IADL's in the Elderly.
      METHOD: This quasi-experimental study was designed for a nonequivalent control
      group repeated measurement study. This study was done from Oct. 13. 2004 to Dec.
      18. 2004. The subjects were between the ages of 65 to 75, who were literate in
      Korean and able to communicate and participate in physical exercise without any
      discomfort. The experimental group was 25 subjects and the control group was 26.
      The 5-week 'Logotherapy with Exercise' program was given to the experimental
      group. Data was analyzed by Chi2, t-test, ANCOVA, ANOVA, and post-hoc comparison
      by Bonferroni correction with the SPSS/WIN 12.0. RESULTS: The experimental group
      had a greater difference in meaning of life, ego integrity and IADL's than the
      control group. The experimental group had differences in changes in meaning of
      life, ego integrity and IADL's during time period. CONCLUSION: 'Logotherapy with
      Exercise' can be recommended as an effective nursing intervention for the
      elderly.

PMID- 16953128
TI  - [Process of seeking positive life of patients with Parkinson's disease].
AB  - PURPOSE: The purpose of this study was to help understand the life and illness
      experiences of focusing on a positive lifestyle, patients with Parkinson's
      disease, METHOD: The present study adopted a ethno graphic methodology. The
      participants for this study were 4 men and 3 women, who were treated for
      Parkinson's disease. Data was collected by an interview and participant
      observations from August 2003 to September 2004. Tape-recorded interviews were
      transcribed after the interview and classified and described to realistic tale.
      RESULT: Patients with Parkinson's disease experienced the stage of retake-off
      pursuing positive life by overcoming the acceptance process of illness including
      the stage of recognition of change, the stage of disruption and the stage of
      acceptance. The factors of positive life of Patients with Parkinson's disease
      were their strong will and social support. CONCLUSION: This study may be used in
      future studies as an important resource to develop nursing intervention
      strategies and programs for patients with Parkinson's disease that can help the
      patients to achieve strong willingness and positive life in Korea.

PMID- 16953129
TI  - [Research trend of complementary and alternative medicine].
AB  - PURPOSE: This study was done to describe the research trend of Complementary and
      Alternative Medicine(CAM) in Korea and internationally. METHOD: A Systematic
      review of CAM related literature published from 2000 to 2005 was done. A
      comprehensive search by using 34 CAM modalities as search terms to identify all
      articles dealing with CAM was undertaken from 4 databases: PubMed, RICHIS,
      KoreaMed, and Riss4U. A Total of 588 abstracts and 223 original articles were
      reviewed by two independent reviewers using systematic analysis guidelines. Data
      regarding the types of study design, characteristics of subjects and researchers,
      and classification of CAM modalities was recorded. The outcome measures of CAM
      were identified. RESULTS: CAM research has been rapidly increasing worldwide in
      the last decade. In Korea, nursing(53.5%) followed by medicine(42.7%) occupied
      the majority of CAM research in comparison to medicine(42.9%) and disciplines in
      CAM(25.0%), like homeopathy, internationally. Prevailing research designs in
      Korea were experimental and quasi-experimental, however, randomized clinical
      trials were found. Internationally, survey research was dominant, with the
      exception of randomized clinical trials that were mostly an experimental design.
      CONCLUSION: The findings suggest that a robust research design in CAM research is
      needed to accumulate strong scientific evidence and to adopt nursing
      interventions from CAM modalities.

PMID- 16953130
TI  - [Effects of non-nutritive sucking on the physiological and behavioral states of
      pre-term infants during tube feeding].
AB  - PURPOSE: This study was to investigate the effects of non-nutritive sucking on
      physiological and behavioral state of pre-term infants during tube feeding.
      METHOD: This nonequivalent, non-synchronized experimental study included 50 pre
      term infants. An attempt was made to match gestational age and birth weight of
      infants in each group. Infants in the experimental group were given a pacifier 2
      minutes before, during, and for 2 minutes after tube feeding. Infants in the
      control group did not get a pacifier. Both groups were tested at three stages for
      changes in the physiologic state and behavioral state--2 minutes before, during,
      and 2 minutes after feeding. Date was analyzed with SPSS WIN 10.0 using an Chi2
      test, t-test, and repeated measures ANOVA. RESULT: Heart rates and oxygen
      saturation levels of the two groups were significantly different(P=.001, P=.000).
      The behavioral states of the two groups were significantly different during and
      post feeding(P=.000, P=.000). CONCLUSION: This result suggests non-nutritive
      sucking by using a pacifier is an effective intervention for pre-term infants
      during tube feeding.

PMID- 16953131
TI  - [Factors associated with success of smoking cessation during 6 months].
AB  - PURPOSE: This study was to identify which factors are likely to influence the
      effectiveness of smoking cessation on adults who smoke in Metropolitan Incheon.
      METHOD: Data from 9,083 smokers, who visited a smoking cessation clinic of a
      public health center from Jan. to Oct. 2005, were provided by the Korean Health
      Research Society. Among 9,083 smokers, 1,495 people were selected for follow up
      care at 6 months in order to analyze the differences between two groups one is a
      successful group and the other is a failure group. RESULTS: The successful group
      included 639 people and the failure group 856 people. In the demographic profiles
      such as sex, age and motive registration, there was a significant difference
      between the two groups. In the view of smoking pattern and factors such as the
      expiratory CO level, the age of starting to smoke, the duration of smoking,
      alcohol, and dependence on alcohol use and nicotine, there were significant
      differences between the two groups. The smoking cessation method, results of uni
      variate analysis, the total number of visits to the smoking cessation clinics,
      and the use of nicotine gum or a patch(stage 1, stage 2) were significantly
      different in the two groups. CONCLUSION: The results of multi variate analysis
      have shown that the factors associated with the success for smoking cessation is
      the total number of visits to the smoking cessation clinic, and the dependence on
      alcohol.

PMID- 16953132
TI  - [The effects of a comprehensive life style modification program on glycemic
      control and stress response in type 2 diabetes].
AB  - PURPOSE: This study was to evaluate the effects of a comprehensive life style
      modification program on glycemic control and stress response in type 2 diabetes.
      METHOD: The participants(n=34) with type 2 diabetes were divided into either a
      usual care(control) or treatment(experimental) group. The experimental
      group(n=21) received a program that was based on a comprehensive life style
      modification protocol at a weekly meeting for 16 weeks. They also participated in
      individually prescribed exercise and diet along with stress management and self
      monitoring. The participants were followed for 6 months, during which
      postprandial glucose, HbA1C, and stress response inventory were measured. RESULT:
      The experimental group showed a significant lower postprandial glucose and stress
      response compared to those of the control group. However, there was no
      significant change in the HbA1C value in either group. CONCLUSIONS: These results
      suggest that a type 2 diabetes comprehensive lifestyle modification program may
      lead to clinical improvement in glycemic control and reduce the stress response.

PMID- 16953133
TI  - [Development of a questionnaire to measure family stress among married working
      women].
AB  - PURPOSE: Even though a number of studies have suggested that appropriate
      measuring instruments of family stress for working women have to be developed,
      the validity and reliability of the instruments used have not been consistently
      examined. The purpose of the present study was to develop a sensitive instrument
      to measure family stress for married working women, and to test the validity and
      reliability of the instrument. METHOD: The items generated for this instrument
      were drawn from a comprehensive literature review. Twenty four items were
      developed through evaluation by 10 experts and twenty one items were finally
      confirmed through item analysis. Psychometric testing was preformed and confirmed
      with a convenient sample of 240 women employed in the industrial sector. RESULT:
      Four factors evolved by factor analysis, which explained 50.5% of the total
      variance. The first factor 'Cooperation' explained 28.1%, 2nd factor
      'Satisfaction with relationships' 10.6%, 3rd factor 'Democratic and comfortable
      environment' 6.3%, and 4th factor 'Disturbance of own living' 5.5%. Cronbach's
      coefficient of this instrument was 0.86. CONCLUSION: The study supports the
      validity and reliability of the instrument.

PMID- 16953134
TI  - [Task analysis of Korean geriatric care managers].
AB  - PURPOSE: This study was designed to create a job description for Korean geriatric
      care managers and examine performance frequency, importance, and difficulty of
      task elements. METHOD: The sample consisted of 38 geriatric care managers and
      professors who performed duties related to geriatric care management at community
      based-facilities in Korea. A survey method was used, and the questionnaire
      included frequency, importance, and difficulty of task elements in job
      descriptions using the DACUM method. Using SPSS WIN 10.0, descriptive statistics
      such as frequency distribution, means, and standard deviation were conducted to
      examine the subject's general characteristics, frequency, importance, and
      difficulties of task performance. RESULT: The job description of geriatric care
      managers revealed 10 duties, 34 tasks, and 105 task elements. On all ten duties,
      the average performance frequency, importance, and difficulty was 2.55, 2.21 and
      2.43 respectively. CONCLUSION: The job description of geriatric care managers
      includes duty, task, and task elements and the definition of a completed job.
      Thus we recommend a data based trial to confirm and validate the information
      gathered.

PMID- 16953135
TI  - [Concept analysis of preparatory grief in terminal cancer patients].
AB  - PURPOSE: The purpose of this study was to conceptualize and clarify a concept of
      "preparatory grief" in terminal cancer patients. METHOD: A hybrid model of
      concept development was applied to develop a concept of preparatory grief, which
      included a field study carried out in Busan, Korea. Participants of this study
      were 8 cancer patients. RESULTS: On the basis of our literature, research and
      clinical experience, the concept of preparatory grief emerged as a complex
      phenomenon playing an important role in five areas; physical, emotional,
      interpersonal, religious, and transcendental dimensions. Two new attributes were
      defined through a field phase; trust of the post-mortal world and a serene state
      of mind. Indicators reflected attitudes of sadness, worry, regret, capability to
      adapt and hope. The results of preparatory grief were loss of energy and
      interest, emotional chaos, contemplation, taciturnity and restoration.
      CONCLUSIONS: Differentiating among preparatory grief and other symptoms in cancer
      patients is essential because of therapeutic implications. Understanding
      preparatory grief is necessary in order to manage cancer patients for promoting
      quality of life so that its application may have a positive impact on the
      patient's life.

PMID- 16953136
TI  - [Adjustment of middle-aged people with hemiplegia after a stroke].
AB  - PURPOSE: The purpose of this study was to understand the adjustment process of
      middle-aged people in Korea with hemiplegia after a stroke. METHOD: For this
      study, the grounded theory method was utilized. RESULTS: After constant
      comparative analysis, the core category emerged as 'rebuilding the body which was
      ruined'. In addition, the causal conditions were 'restriction of physical
      function', and 'loss of roles'. The adjustment process consisted of the 'facing
      reality phase', 'overcoming depression phase', 'overcoming physical limits phase'
      and 'reestablishing roles phase'. The main strategies in the facing reality phase
      were 'holding on to a glimmer of hope', 'getting away from the harsh reality' and
      'facing up to the reality'. The main strategies in the overcoming depression
      phase were 'soothing oneself', 'Self-introspection' and 'restoring self-esteem'.
      In addition, the main strategies in the self-initiative overcoming physical
      limits phase was 'discovering personal strategies and striving to recover'. The
      main strategies in the reestablishing roles phase were 'reestablishing a parents'
      role', 'reestablishing a spouse's role' and 'reestablishing social roles'.
      CONCLUSION: In conclusion, even though many middle aged stroke patients remained
      in the depression phase, most of them who overcame depression strived to conquer
      physical limits on their own initiative.

PMID- 16953137
TI  - [Concept analysis of spiritual care].
AB  - PURPOSE: The purpose of this study was to identify attributes of the concept of
      spiritual care. METHOD: Walker and Avant's concept analysis framework was
      employed to review the clinical guidelines, nursing text books, and nursing
      research articles which were related to spiritual care and published from 1985 to
      2005. RESULT: The attributes of the concept of spiritual care were a three stage
      process such as spiritual assessment, spiritual intervention, and spiritual
      evaluation. Spiritual care included three dimensions of relationships such as
      transpersonal, interpersonal, and intrapersonal. The quality of spiritual care
      was dependent upon characteristics of care-givers such as perception and
      knowledge of spiritual care, and the clinical environment. The antecedents of
      spiritual care was spiritual needs due to the prompt events. The consequence of
      spiritual care was spiritual well-being. CONCLUSION: This concept analysis of
      spiritual care contributed to promote performance of spiritual care in clinical
      fields by removing conceptual ambiguity and confirming the true meaning of
      spiritual care.

PMID- 16953138
TI  - [Effects of individual reminiscence therapy on older adults' depression, morale
      and quality of life].
AB  - PURPOSE: This study examined the effects of individual reminiscence therapy on
      older adults' depression, morale, and the quality of life. METHODS: The design
      was a single-group pre-test and post-test study. Subjects consisted of 31 older
      adults from two senior centers and a welfare center in Seoul. Individual
      reminiscence therapy was applied to study subjects four times, once a week for an
      hour at each time. Measurement tools were the Geriatric Depression Scale Short
      Form Korea (GDSSF-K) for depression, Mun Ae-ri's (1996) scale for morale, and
      Medical Outcomes Study Short Form 36 (SF-36) for the quality of life. Data was
      analyzed using descriptive statistics, paired t-test, and pearson correlation.
      RESULTS: The application of individual reminiscence therapy reduced older adults'
      depression (t=-5.65, p=.000), and enhanced older adults' morale (t=4.65, p=.000).
      The application of individual reminiscence therapy improved older adults' quality
      of life (t=5.00, p=.000). CONCLUSION: Findings of the study suggest that
      individual reminiscence therapy may be applied as a nursing intervention that
      contributes to the improvement of older adults' quality of life, reduces their
      depression, and enhances their morale.

PMID- 16953139
TI  - [Association of anger expression patterns and health status in health care
      workers].
AB  - PURPOSE: The purpose of this study was to examine anger-expression patterns and
      their association with state and trait anger and physical and psychological
      health status in health care workers. METHOD: Four hundred and forty eight
      nurses, physicians and technicians from a large medical center completed
      standardized questionnaires of anger, anger-expression patterns and mood. They
      also had blood pressure, cholesterol, blood glucose and body mass index measured
      during their annual physical examinations. Data was analyzed using descriptive
      statistics, independent t-test, chi-square and ANOVA. RESULTS: Subjects showed
      two major clusters of anger-expression patterns: anger-control and anger-in/out.
      Subjects with the anger-in/out pattern reported higher state and trait anger and
      more anxiety, depression and fatigue than subjects with the anger-control
      pattern. Physical health indicators, however, were not significantly different
      between the two clusters of anger-expression patterns. CONCLUSION: Anger
      expression patterns are associated with psychological health status but not with
      physical health status. Anger-expression patterns, however, need to be examined
      over time to assess their long-term effects on the physical and psychological
      health status in future studies.

PMID- 16953140
TI  - [Prevalence and associated factors of excessive daytime sleepiness in adults].
AB  - PURPOSE: The purpose of the present study was to identify prevalence of excessive
      daytime sleepiness(EDS) and its associations with sleep habits, sleep problems,
      depression, subjective health status and obesity in community dwelling adults.
      METHOD: Data was collected from adults aged 20-59 years by random sampling.
      Subjects completed a questionnaire which was composed of the Epworth Sleepiness
      Scale, Center for Epidemiologic Studies Depression Scale, and questions that
      included items about sleep habits, sleep problems, subjective health status and
      sociodemographic characteristics. Height and weight were measured for calculation
      of body mass index. The statistical analyses was based on 3,302 adults (51.5%
      males and 48.5% females). Descriptive statistics, univariate logistic regression
      and multiple logistic regression were used. RESULT: The prevalence of EDS was
      17.1%. Multiple logistic regression showed that the associated factors of EDS
      were depression, obesity, dissatisfaction with sleep time, irregular sleep, and
      habitual snoring. Depression was the most significant associated factor(adjusted
      odds ratio for severe depression=2.27, 95% Confidence Interval=1.73-2.96).
      CONCLUSION: EDS is a common symptom in adults. Our finding suggested that persons
      with a complaint of EDS should be completely assessed for depression and obesity
      as well as sleep problems.

PMID- 16953141
TI  - [Body fat distribution and blood pressure according to anthropometric change in
      Korean patients with non-insulin dependent diabetes mellitus (NIDDM)].
AB  - PURPOSE: This study was done to identify fat distribution and blood pressure
      according to anthropometric change patterns between NIDDM patients and control
      subjects. METHODS: Cross-sectionally 167 NIDDM patients and 87 controls were
      studied. Previous maximal body weight and acute weight loss was obtained. Current
      height, body weight, BMI, waist-hip ratio (WHR), skinfold thicknesses(abdomen,
      subscapular and triceps), and blood pressure was measured. Three anthropometric
      change patterns were categorized by BMI changes from the maximum lifetime's BMI
      to the current time (obese-obese, obese-nonobese and nonobese-nonobese: obese:
      BMI > or =25 kg/m2, nonobese: BMI<25 kg/m2). The data was analyzed by Chi2, t
      test, age adjusted ANCOVA and Least Squares Means (LSM) for multiple comparison.
      RESULT: Acute body weight loss (p=0.01), anthropometric change types (p=0.001),
      WHR (P=0.05), and skinfold thickness (p=0.002) of NIDDM were significantly higher
      than those of the controls. The mean arterial pressure, WHR and skinfold
      thicknesses were greater in both obese-obese and obese-nonobese NIDDM and control
      subjects compared with both nonobese-nonobese NIDDM and control subjects. (all
      p's<0.05). CONCLUSION: NIDDM patients had more central and upper body
      adiposicity. Also both obese-obese and obese-nonobese NIDDM and control subjects
      had higher mean arterial pressures and central body obesity.

PMID- 16953142
TI  - [Factors influencing the emotional state of patients with lymphedema].
AB  - PURPOSE: The purpose of this study was to investigate the emotional state and
      related factors in patients with lymphedema. METHODS: The subjects of this study
      consisted of 95 patients with lymphedema at 8 hospitals in Busan and Seoul. Data
      was collected by a self-administered questionnaire between March 2001 to December
      2001. Data was analyzed by Pearson correlation coefficient, and stepwise multiple
      regression using SPSS Win 12.0. RESULTS: The mean score of the emotional state of
      the subjects was 3.06; of their physical symptoms, 1.84; of their Activities of
      Daily Living(ADLs), 2.30; and of their social activities, 3.67. The emotional
      states of lymphedema patients correlated with their physical symptoms, their
      ADLs, and their social activities. The Factor influencing the emotional state of
      the subjects was social activities. CONCLUSION: These results suggest that a
      negative emotional state is very common in patients with lymphedema, to which
      appropriate attention should be given. Rehabilitation programs must be
      implemented to improve lymphedema patients' emotional state, physical symptoms,
      ADLs, and social activities.

PMID- 16953143
TI  - [Factors influencing functional status in patients with heart failure].
AB  - PURPOSE: The purpose of this study was to identify the factors that influence the
      functional status of patients with heart failure. METHOD: A descriptive,
      correlational study design was used. The participants in this study were 260
      patients with heart failure who were admitted at Y University and U University in
      Seoul, Korea. Between September 2005 and December 2005 data was collected by an
      interview using a questionnaire and from medical records. The Functional status
      was measured with KASI. Physical factors (dyspnea, ankle edema, chest pain,
      fatigue, and sleep dysfunction), psychological factors (anxiety and depression),
      and situational factors (self-management compliance and family support) were
      examined. RESULT: In general, the functional status, anxiety, depression, self
      management compliance, and family support was relatively not good. The level of
      fatigue was highest and the level of ankle edema was lowest for physical symptom
      experiences. In regression analysis, functional status was significantly
      influenced by dyspnea(23%), age(13%), monthly income(7%), fatigue(3%), ankle
      edema(2%), depression(1%), and length of stay in the hospital(1%). These factors
      explained 50% of the variables in the functional status. CONCLUSION: These
      results suggest that psycho-physiological symptoms management should be a focus
      to improve the functional status in patients with heart failure.

PMID- 16953144
TI  - [Anger, cardiovascular health and depression in middle-aged Korean men: the
      mediating effect of social support].
AB  - PURPOSE: A descriptive correlational study was designed to examine the
      relationship of trait anger and anger expression to blood pressure, cholesterol,
      and depression in middle-aged Korean men. In addition, this study investigated
      the mediating effect of social support in relation to anger and other variables.
      METHODS: Two hundred and ninety nine men aged 40 to 64 years were recruited from
      a health center at K University Hospital located in Ansan City, Kyungki province,
      Korea. The instruments used were Spielberger's state trait anger expression
      inventory-the Korean version for trait anger and anger expression, Beck's
      depression inventory for depression, and a Personal resource questionnaire for
      perceived social support. RESULTS: Men with high trait anger showed significantly
      higher systolic blood pressure(BP) and diastolic BP. The level of cholesterol did
      not have a significant relationship with trait anger and anger expression. The
      severity of depression was significantly higher in men with high trait anger or
      more frequent uses of anger-in or anger-out. The perceived social support had a
      significant mediating effect in relation to trait anger and depression.
      CONCLUSIONS: Various nursing interventions for managing anger or improving social
      support need to be developed in a future study.

PMID- 16953145
TI  - Obesity: a main factor of metabolic syndrome?
AB  - The metabolic syndrome (MS) is a common metabolic disorder that has been recently
      related to the increasing prevalence of obesity. The disorder is defined in
      various ways, but in the near future a new definition(s) will be applicable
      worldwide. The pathophysiology has been largely attributed, in the past years, to
      insulin-resistance, even if several epidemiological and pathophysiological data
      are attractive to indicate visceral obesity as a main factor in the occurrence of
      the MS, promoting new definitions and re-evaluation of the pathogenesis of this
      syndrome. In this review, we have analyzed the role of visceral obesity in the
      new definition of the MS such as the pathophysiological role of the abnormal fat
      distribution in the occurrence of this syndrome. In view of this, relationships
      between visceral obesity, free fatty acids, dyslipidaemia and insulin-resistance
      have been reported. In addition, the effects of some adipocytokines and other
      proinflammatory factors produced by fat accumulation on the appearance of the MS
      have been also emphasized. Finally, according to recommendations of several
      international societies, the role of the life-style change and of the weight loss
      in the prevention and treatment both of obesity and of other associated risk
      factors has been analyzed.

PMID- 16953146
TI  - Stem cell strategies for Alzheimer's disease therapy.
AB  - We have found much evidence that the brain is capable of regenerating neurons
      after maturation. In our previous study, human neural stem cells (HNSCs)
      transplanted into aged rat brains differentiated into neural cells and
      significantly improved the cognitive functions of the animals, indicating that
      HNSCs may be a promising candidate for cell-replacement therapies for
      neurodegenerative diseases including Alzheimer's disease (AD). However, ethical
      and practical issues associated with HNSCs compel us to explore alternative
      strategies. Here, we report novel technologies to differentiate adult human
      mesenchymal stem cells, a subset of stromal cells in the bone marrow, into neural
      cells by modifying DNA methylation or over expression of nanog, a homeobox gene
      expressed in embryonic stem cells. We also report peripheral administrations of a
      pyrimidine derivative that increases endogenous stem cell proliferation improves
      cognitive function of the aged animal. Although these results may promise a
      bright future for clinical applications used towards stem cell strategies in AD
      therapy, we must acknowledge the complexity of AD. We found that glial
      differentiation takes place in stem cells transplanted into amyloid-( precursor
      protein (APP) transgenic mice. We also found that over expression of APP gene or
      recombinant APP treatment causes glial differentiation of stem cells. Although
      further detailed mechanistic studies may be required, RNA interference of APP or
      reduction of APP levels in the brain can significantly reduced glial
      differentiation of stem cells and may be useful in promoting neurogenesis after
      stem cell transplantation.

PMID- 16953147
TI  - Hyperphosphorylation of tau and protein phosphatases in Alzheimer disease.
AB  - Aggregation of abnormal hyperphosphorylated tau to neurofibrillary tangles in
      affected neurons is one of the hallmarks for Alzheimer disease (AD). Studies
      during the last decade have strongly suggested that hyperphosphorylation of tau
      is site-specifically responsible for the loss of biological activity, the gain of
      toxic activity, and the aggregation into paired helical filaments. Hence, the
      abnormal hyperphosphorylation of tau appears to be critical to the pathogenesis
      of AD. The state of tau phosphorylation is controlled by a balance between tau
      phosphatase(s) activity and tau kinase(s) activity. Many studies have shown that
      hyperphosphorylation of tau in AD brain might be due to decreased tau
      phosphatase(s) activity. This article reviews the recent research advances in
      regulation of tau phosphorylation by phosphoseryl/phosphothreonyl protein
      phosphatases, and also summarizes the role of each tau phosphatase on abnormal
      hyperphosphorylation of tau in AD brain.

PMID- 16953148
TI  - Gastric precancerous changes: carcinogenesis, clinical behaviour immunophenotype
      study and surveillance.
AB  - Gastric cancer (GC) is the second most common cause of cancer-related death
      worldwide. Two-thirds of the GC patients are diagnosed in advanced stages, when
      surgery can only be a palliative. When the diagnosis is made at an early stage,
      the surgical treatment results in 10 years survival rates are higher than 85%.
      From the critical evaluation of the literature data we can affirm that there are
      some obstacles to an exclusive acceptance of the idea that the relation of
      Helicobacter pylori (H. pylori) infection with noninvasive (formerly dysplasia)
      or invasive neoplastic modifications solely develop by means of chronic gastritis
      with its atrophic evolution and achlorhydria. Intestinal metaplasia as a
      precursor of GC has been overemphasized and doubts persist about the real
      necessity to operate histologically a subdivision into subtypes. The extent of
      the metaplastic process is probably more important that the metaplastic subtype.
      The evaluation of the clinical behaviour shows how low grade noninvasive
      neoplasia is associated with or progressed to GC in about 9% of cases, while high
      grade noninvasive neoplasia is associated with or progressed to GC in about 75%
      of cases, thus proving to be a real histological marker of GC. The subdivision of
      the cases according to the TNM classification demonstrates that, in most of the
      cases, early GC is present (43/45: 95.5%). An appropriate endoscopy follow-up
      with biopsies according to well defined criteria increases the likelihood of
      invasive neoplasia being detected in its early stage with a better postsurgical
      prognosis. Noninvasive neoplasia is characterized by severe alterations of the
      immunophenotype profile in association with a high proliferation index and
      frequent p53 mutations. The choice to address the patients to surgical
      intervention could be made not only on the basis of histochemical techniques, but
      also with the help of immunohistochemical evaluations.

PMID- 16953149
TI  - Development of a quantitative-competitive PCR for quantification of human
      cytomegalovirus load and comparison with antigenaemia, viraemia and pp67 RNA
      detection by nucleic acid sequence-based amplification.
AB  - AIM: The human cytomegalovirus (HCMV) is an important pathogen in
      immunocompromised patients, such as transplant recipients. The use of sensitive
      and rapid diagnostic assays can have a great impact on antiviral prophylaxis and
      therapy monitoring and diagnosing active disease. Quantification of HCMV DNA may
      additionally have prognostic value and guide routine management. The aim of this
      study was to develop a reliable internally-controlled quantitative-competitive
      PCR (QC-PCR) for the detection and quantification of HCMV DNA viral load in
      peripheral blood and compare it with other methods: the HCMV pp65 antigenaemia
      assay in leukocyte fraction, the HCMV viraemia, both routinely employed in our
      laboratory, and the nucleic acid sequence-based amplification (NASBA) for
      detection of HCMV pp67-mRNA. METHODS: Quantitative-competitive PCR is a procedure
      for nucleic acid quantification based on co-amplification of competitive
      templates, the target DNA and a competitor functioning as internal standard. In
      particular, a standard curve is generated by amplifying 10(2) to 10(5) copies of
      target pCMV-435 plasmid with 10(4) copies of competitor pCMV-C plasmid. Clinical
      samples derived from 40 kidney transplant patients were tested by spiking 10(4)
      copies of pCMV-C into the PCR mix as internal control, and comparing results with
      the standard curve. RESULTS: Of the 40 patients studied, 39 (97.5%) were positive
      for HCMV DNA by QC-PCR. While the correlation between the number of pp65-positive
      cells and the number of HCMV DNA genome copies/mL and the former and the pp67mRNA
      positivity were statistically significant, there was no significant correlation
      between HCMV DNA viral load assayed by QC-PCR and HCMV viraemia. CONCLUSIONS: The
      QC-PCR assay could detect from 10(2) to over 10(7) copies of HCMV DNA with a
      range of linearity between 10(2) and 10(5) genomes.

PMID- 16953150
TI  - Improving outcomes in tumour necrosis factor a treatment: comparison of the
      efficacy of the tumour necrosis factor a blocking agents etanercept and
      infliximab in patients with active rheumatoid arthritis.
AB  - AIM: The aim of this study was to evaluate the differences between infliximab and
      etanercept, in terms of clinical efficacy and rapidity of action. METHODS: We
      selected 32 patients with rheumatoid arthritis (RA) with an incomplete response
      to disease modifying anti-rheumatic drugs (DMARDs), and randomly assigned them to
      etanercept or infliximab. We evaluated the efficacy after 14, 22, 54 weeks of
      treatment, using the American College of Rheumatology (ACR) 20, 50 and 70
      criteria, and the improvement of quality of life using the Health Assessment
      Question-naire (HAQ). RESULTS: After 14 weeks, the 54.4% of patients was
      considered ACR-responders in the etanercept group, whereas, in the infliximab
      group, the percentage of responders was 74.4%: infliximab gave better results for
      the tender joint count and for physician's global assessment. After 22 weeks, no
      significant difference was present. After 54 weeks, etanercept resulted more
      effective than infliximab for tender joint count (TJC) value, for visual analogic
      scale (VAS) for pain score, for global disease assessment value, with 74.4% of
      patients considered ACR-responders in the group treated with etanercept and 60%
      in the group treated with infliximab. As regards HAQ, patients in the infliximab
      group presented higher scores at week 14, but in weeks 22 and 54, patients in the
      etanercept group showed better results. Therefore, both infliximab and etanercept
      are efficacious in RA, but infliximab is more efficacious than etanercept in week
      14. Vice versa, in week 54 etanercept is the most efficacious drug. CONCLUSIONS:
      Physicians have 2 weapons in their armamentarium, with the same target but
      distinct clinical, pharmacokinetic and pharmacodynamic properties.

PMID- 16953151
TI  - Hypokalemic nephropathy in an adult patient with partial empty sella: a classic
      Bartter's syndrome, a Gitelman's syndrome or both?
AB  - Bartter's syndrome belongs to a group of hypokalemic renal channel diseases.
      These channels are located in the lipid layer of cell membranes where they exist
      as water channels through which ion transport is performed. Based on the type of
      genetic disorder and clinical presentation, Bartter's syndrome is classified as
      neonatal, classical and Gitelman's syndrome. Most of the cases have been noted in
      pediatric age groups and adult-onset cases are very rare. Moreover, an
      association between Bartter's syndrome and empty sella has recently been reported
      in 3 children. We report here the second case of an adult patient affected by
      Bartter's syndrome with partial empty sella. The patient showed some clinical and
      histological characteristics of both classic Bartter's syndrome and Gitelman's
      syndrome, suggesting that genotype and phenotype of Bartter's syndrome are not so
      clear-cut and that phenotypic overlap may occur, according to a recent
      hypothesis. Magnetic resonance imaging disclosed a partial empty sella. A
      thorough endocrinological investigation showed normal hypophyseal, thyroidal,
      adrenal and gonadal function. Good therapeutic effects were achieved using
      spironolactone, ACE-inhibitor and potassium supplementation, with normalization
      of the kalemia. At present, the value of the association of Bartter's syndrome
      and empty sella remains unclear and future studies are needed to clarify the
      importance of this association, both in children and in adult patients affected
      by Bartter's syndrome.

PMID- 16953152
TI  - Obesity, insulin-like growth factors and colorectal cancer.

PMID- 16953153
TI  - Exclusion of chromosome region 22q12.1-q12.3 as a second locus for Costello
      syndrome.

PMID- 16953154
TI  - Eustachian valve and pulmonary embolism.

PMID- 16953156
TI  - Is above knee bypass defunct?
AB  - As endovascular treatments improve, the inevitable progress will result in the
      abandonment of conventional bypasses. First and foremost in this regard is the
      use of above knee bypass, particularly with prosthetic graft material. Already,
      endovascular success approaches or exceeds the patency seen with this bypass
      technique. As a result, in centers with endovascular expertise in infrainguinal
      intervention, bypass surgery is increasingly being replaced by these techniques
      and conventional bypass surgery is disappearing. Over the next few years, above
      knee bypass will be replaced by endovascular techniques in most centers as our
      results with these techniques improve.

PMID- 16953157
TI  - Remote superficial femoral artery endarterectomy and distal aSpire stenting:
      results of a multinational study at three-year follow-up.
AB  - AIM: The aim of this study was to examine the results of remote superficial
      femoral artery endarterectomy (RSFAE) in conjunction with distal aSpire stenting
      in a multinational study. METHODS: RSFAE is a minimally invasive procedure
      performed through a limited groin incision. A total of 210 patients were included
      in this study. The indications for the procedure were claudication in 158 (75%)
      patients and limb salvage in 52 (25%). After RSFAE the outflow tract atheromatous
      plaque was ''tacked'' with the aSpire stent, which is an expanded
      polytetrafluoroethylene (ePTFE) covered nitinol stent with high radial strength,
      yet it is flexible enough to withstand the compressive forces at the knee joint.
      Prior to stent deployment, if the stent position is not in optimal position, it
      can be ''wrapped down'', repositioned and re-expanded. Therefore, not only is the
      plaque end point tacked, but the collaterals are preserved as well. All patients
      underwent follow-up examination with serial color-flow duplex ultrasound
      scanning. RESULTS: The mean length of endarterectomized superficial femoral
      arteries (SFAs) was 28.2+/-6.2 cm (range 15-43 cm). The primary cumulative
      patency rate by means of life-table analysis was 60.6+/-4.8% (SE) at 33 months,
      (mean 17.1 months; range 1-33 months). During follow-up percutaneous transluminal
      balloon and/or stent angioplasty was necessary in 50 patients for a primary
      assisted patency of 70.2+/-4.8% at 33 months. The locations of the restenosis
      after RSFAE were evenly distributed along the endarterectomized artery. There
      were 2 deaths (myocardial infarctions), 12 (5.7%) wound complications (7
      hematomas, 5 skin edge sloughs) and the mean hospital length of stay was only
      1.3+/-0.5 days. CONCLUSION: RSFAE with distal aSpire stenting is a minimally
      invasive, safe durable procedure for the treatment of long-segment SFA occlusive
      disease.

PMID- 16953158
TI  - Will absorbable metal stent technology change our practice?
AB  - Peripheral stents aim to support revascularization procedures of intravascular
      stenoses by mechanically preventing vessel recoil and counteracting
      pathophysiologic processes of luminal re-narrowing triggered by procedural injury
      of the vessel wall. Despite improvements in stenting techniques and concomitant
      medication, repeated intervention due to target lesion re-stenosis is necessary
      on a significant percentage of patients. The permanent presence of an artificial
      implant plays a prominent role in the discussion of mechanisms causing in-stent
      restenosis. Permanent metallic implants pose the risk of a continuous interaction
      between non-absorbable stent and surrounding tissue, leading to physical
      irritation, long-term endothelial dysfunction, or chronic inflammatory reactions.
      In addition, there is a risk of stent fracture due to external mechanical forces.
      To overcome these shortcomings, technology of stenting has moved towards the
      development of temporary implants composed of biocompatible materials which
      mechanically support the vessel during the period of high risk for recoil and
      then completely degrade in the long-term perspective. This removes a potential
      trigger for late restenosis.

PMID- 16953159
TI  - Subintimal angioplasty in the management of lower limb ischaemia.
AB  - It is now almost 20 years since subintimal angioplasty (SIA) was pioneered. This
      cost-effective technique has over the past few years enjoyed a dramatic
      resurgence of interest and application, particularly after having been identified
      as a safe and practicable approach to vascular recanalisation in several
      international publications. Originally used in the femoropopliteal segment, its
      role has been extended to the treatment of infrapopliteal lesions, including the
      recanalization of the trifurcation and long tibial occlusions. Experienced
      centres have repeatedly reported primary success rates of around 90% in the
      infrainguinal vessels, as well as 1-year limb salvage rates as high as 85% to
      90%, and 5-year primary assisted patency rates of 64% whilst not interfering with
      subsequent vascular surgery. Indeed SIA has not only proved to be very effective
      in lower limb ischaemia management, both for intermittent claudication and
      critical ischaemia, but in the last few years it has moved from the shadows and
      into the limelight of modern endovascular therapy.

PMID- 16953160
TI  - Results with heparin bonded polytetrafluoroethylene grafts for femorodistal
      bypasses.
AB  - AIM: Expanded polytetrafluoroethylene (ePTFE) grafts are commonly used for
      femoropopliteal (FP) and femorocrural (FC) bypass grafting. Especially in below
      knee (BK) reconstructions, patency is often inferior to the outcome in patients
      eligible for venous bypass grafting. This study assesses whether the Carmeda
      BioActive Surface (CBAS), which employs covalent end-point linkage to retain
      heparin on the device surface, as it is used on the Propaten vascular graft
      successfully, can prolong patency. METHODS: From June 2002 to December 2005, 138
      patients (97 men and 41 women; mean age: 73 years) received the CBAS-ePTFE graft
      for 153 infrainguinal bypass procedures. Seventy-five above-knee (AK) and 78 BK
      (including 37 FC) procedures were performed. Follow-up evaluations consisted of
      clinical examinations, ultrasonographic studies, and distal pulse assessments.
      Patency and limb salvage rates were assessed by using life-table analyses.
      RESULTS: The overall primary and secondary 2-year patency rates were 73.6% and
      86%, respectively. Two-year primary patency rates according to bypass type were
      76.2%, 72.6%, and 68.9% for AK FP, BK FP, and FC bypasses, respectively; the
      corresponding secondary patency rates were 87.5%, 87.8%, and 79.4%. The 2-year
      limb salvage rate in patients with critical limb ischemia (n=68) was 89.9%.
      CONCLUSION: Our findings show that CBAS-ePTFE bypass grafts appear to give
      prolonged patency rates and indicate that the use of this graft may represent a
      viable alternative for BK bypasses, which have traditionally yielded less than
      desirable outcomes. A prospective randomized trial is required to provide more
      definitive information about the graft's patency and limb salvage performance.

PMID- 16953161
TI  - Minimally invasive distal limb bypasses. Techniques and results.
AB  - As endovascular procedures increasingly become the procedures of choice for limb
      salvage, a subset of patients remains that requires open arterial reconstruction
      due to anatomic or pathologic reasons. Traditional greater saphenous vein harvest
      performed during open bypass for peripheral occlusive arterial disease is
      associated with long surgical incisions, increased operative times devoted to
      wound closure, and wound complications such as infection and dehiscence.
      Endoscopic conduit harvest, used with excellent results in coronary artery bypass
      surgery, can also be used in minimally invasive arterial bypass for limb salvage
      with certain technical modifications. These approaches to complex limb salvage
      procedures may result in shortened operating room time, shorter length of stay,
      reduced readmissions for wound complications, and ultimately, decreased costs to
      the health care system. The treating surgeon must continue to stay up to date
      with these approaches and be aware of pertinent issues regarding open and
      minimally invasive arterial interventions, as well as endovascular approaches.

PMID- 16953162
TI  - Filling of the aneurysmal sac with DEAC-glucosamine in an animal model of
      abdominal aortic aneurysm following stent-graft repair.
AB  - AIM: The aim of this study was to present the preliminary results of a technique
      of abdominal aortic aneurysm (AAA) sac filling in an attempt to obliterate the
      sac in a swine AAA model, using deacetylated-poly-N-acetyl glucosamine (DEAC-poly
      N-acetyl glucosamine). METHODS: Eleven Yucatan pigs, 6 months of age, 40 kg -60
      kg, were used to create an AAA with a Dacron pouch implanted surgically and left
      to mature for 2 weeks. One animal was used to establish the AAA creation
      procedures. Eight animals were used for AAA sac filling; of the 8 subjects 2 were
      used for acute studies, and 6 for longer-term studies. Two additional animals
      were used as controls without polymer sac filling. Two weeks after the AAA
      creation, a 13 mmx5.5 cm straight tube AneuRx stent-graft was placed to exclude
      the aneurysm. The aneurysmal sac was filled with a polymer, DEAC-poly-N-acetyl
      glucosamine at 1.5%, 70% deacetylated, mixed with iohexol. There was filling of a
      lumbar artery by the polymer in 2 animals. Endpoints were at 1, 2, 4, 6, 12 and
      24 weeks, in the chronic study animals and 6 and 12 weeks in the control
      subjects, procedures consisting of aortography followed by necropsy and
      pathologic examination. RESULTS: The AAA creation and aneurysm sac filling was
      successful in all animals. An organized thrombus layer of about 2 mm in thickness
      was observed in all subjects along the Dacron aneurysm wall. All aneurysms were
      angiographically patent at the time of treatment, but fresher thrombus within the
      sac was seen in 4 subjects before the polymer injection. The stent-graft
      placement excluded the AAA sac and the polymer injection filled all AAA sacs. The
      AAA sac had acquired a firm rubbery consistency at the time of necropsy. There
      was mild inflammatory reaction to the Dacron material in the surrounding tissues
      and within the sac, to a lesser extent. Two animals developed paralysis of the
      hind limbs following treatment, most likely related to spinal ischemia, and were
      used as acute subjects. There was no recanalization of the aneurysm sac, during
      the follow-up time, ranging from 1 to 24 weeks in the treatment or control
      subjects. There was a 25% shrinkage of the AAA sac at 6th, 40% at 12th week and
      75% by the 24th week. The 2 control subjects showed shrinkage of less than 25% at
      6 and 12 weeks. There was replacement of the polymer/thrombus complex by
      connective tissue, fat tissue with capillary neovascularization in the treated
      subjects. Fibrosis and calcifications were also detected within the sac, mostly
      around the stent-graft and in contact with the aortic wall starting at 4 weeks.
      Control subjects did not show replacement of the thrombus by connective tissue or
      neovascularization. CONCLUSION: The results of this preliminary study support the
      aneurysm sac filling as a potential tool to exclude the aneurismal sac, promoting
      shrinkage of the AAA. DEAC -poly-N-acetyl glucosamine promotes clotting within
      the AAA sac with progressive replacement by connective tissue and
      neovascularization and may have a potential to prevent endoleaks. The polymer is
      easy to use, and it seems to have adequate gradual long-term replacement
      properties, preventing aneurysm sac recanalization.

PMID- 16953163
TI  - Clinical results of autologous infrainguinal revascularization using grafts
      originating distal to the femoral bifurcation in patients with mild inflow
      disease.
AB  - AIM: Chronic critical limb ischemia (CLI) often requires venous bypass grafting
      to distal arterial segments. However, graft patency is influenced by the length
      and quality of the graft and occasionally patients may have limited suitable
      veins. We investigated short distal bypass grafting from the superficial femoral
      or popliteal artery to the infrapopliteal, ankle or foot arteries, despite
      angiographic alterations of inflow vessels, providing that invasive pressure
      measurement at the site of the planned proximal anastomosis revealed an inflow
      brachial pressure difference of <or=10 mmHg. METHODS: Four hundred and twenty
      three consecutive infrainguinal bypass grafts were performed for CLI between
      June, 1999 and November, 2002 at our institution. All patients underwent
      preoperative clinical examination, arteriography and assessment of the veins by
      duplex ultrasound. The study group are patients in whom the proximal and distal
      anastomoses of the bypass are below the femoral bifurcation and the popliteal
      artery, respectively. Invasive arterial pressure measurements were recorded at
      the level of the planned proximal anastomosis which was performed at that level
      if the difference of the inflow-brachial pressure was <or=10 mmHg, irrespective
      of angiographic alterations of the inflow vessels proximal to the planned
      anastomosis. All patients had a clinical follow-up included a duplex examination
      of their graft, at 1 week, 3, 9 and 12 months and, thereafter, annually. No
      patient was lost to follow-up. RESULTS: Sixty-seven patients underwent 71 short
      distal bypass grafts in 71 limbs with reversed saphenous vein grafts in 52, in
      situ saphenous veins in 11, reversed cephalic vein in 1 and composite veins in 7,
      respectively. Surgical or endovascular interventions to improve inflow were
      required in 4 limbs (5.6%). The mean follow-up time was 22.5 months and the two
      year survival was 92.5%. Primary and secondary patency rates at 2 years were 73%
      and 93%, respectively, and the limb salvage rate was 98.5%. CONCLUSION: In
      appropriately selected patients, short distal venous bypass grafts can be
      performed with satisfactory patency and limb salvage rates even in the presence
      of morphologic alterations of the inflow vessels providing that these are not
      hemodynamically significant, or can be corrected intraoperatively.

PMID- 16953164
TI  - Attenuation of acute lung injury following lower limb ischemia/reperfusion: the
      pharmacological approach.
AB  - AIM: The purpose of this study was to examine the effects of N-acetylcysteine
      (NAC), calcium dobesilate (DOBE) and aprotinin on the amelioration of lung damage
      following ischemia/reperfusion injury in a rat hind limb model. A well known
      antioxidant dimethyl-sulfoxide (DMSO) was also tested for comparison. METHODS:
      Ischemia was induced in the lower limb for 4 h by vascular clamping and followed
      by 1 h of reperfusion. Lung injury was evaluated in 5 groups as a saline
      (control), DMSO, NAC, DOBE and aprotinin group. Plasma creatine kinase, lactate
      dehydrogenase, thiobarbituric acid reactive substances (TBARS) as well as lung
      tissue TBARS levels were measured. Lung tissue samples were taken for
      histological examination. P<0.005 was considered statistically significant.
      RESULTS: Plasma TBARS values were found to be significantly lower in the DMSO
      (P<0.005), NAC (P<0.005) and aprotinin (P<0.005) groups compared to the control
      group. Lung TBARS values were significantly lower in the DMSO, NAC, DOBE and
      aprotinin groups compared to the control group (P<0.001, P<0.001, P<0.001). Also
      in the aprotinin group lung TBARS values were found to be significantly lower
      compared to DMSO (P<0.001), NAC (P<0.001) and DOBE (P<0.001) groups. Histological
      examination showed less prominent peribronchial leukostasis (P<0.005) and
      interstitial leukostasis (P<0.005) in all drug groups compared to the control
      group. CONCLUSION: These observations indicate that DOBE and NAC, which are known
      to have antioxidant properties and aprotinin, a serine proteinase inhibitor,
      acted effectively on the prevention of lung injury in a rat hind limb
      ischemia/reperfusion model. The reason why aprotinin exerts a more protective
      effect than the other drugs is not clear, however, its clinical use may have the
      dual advantage of hemostasis and lung protection in surgical practice.

PMID- 16953165
TI  - Apolipoprotein E4 genotype increases the risk of postoperative cognitive
      dysfunction in patients undergoing coronary artery bypass graft surgery.
AB  - AIM: The aim of this study was to investigate the association between the
      presence of ApoE4 and the incidence of postoperative cognitive dysfunction (POCD)
      after cardiac surgery. METHODS: Eighty-seven adult patients undergoing elective
      coronary artery bypass graft surgery were observed prospectively at a university
      tertiary care hospital. All patients were evaluated with the Mini-Mental State
      Examination (MMSE) and the Glasgow Coma Scale (GCS) for cognitive function and
      mental status preoperatively, 24 h after surgery and at postoperative day 6.
      Patients were genotyped for the ApoE polymorphism. The association between ApoE
      genotype and MMSE evolution was studied by using repeated measures ANOVA.
      RESULTS: Both the presence of at least one ApoE4 allele and POCD were verified in
      21.8% of subjects. The presence of the ApoE4 allele was significantly associated
      with a worse MMSE score evolution (P=0.04). CONCLUSION: This study suggests an
      association between ApoE4 and early POCD, but further studies are needed to
      clarify a causative association. Such new studies should include a more
      homogenous patient sample and a longer follow-up.

PMID- 16953166
TI  - Usefulness of the axillary artery as vascular access for cardiopulmonary bypass.
AB  - AIM: In this paper we report our clinical experience with extended utilization of
      axillary artery cannulation for cardiopulmonary bypass (CPB) and discuss the
      indications and the results of the procedure in terms of complications and
      usefulness. METHODS: Between January 1999 and May 2004, 26 patients underwent
      right axillary artery cannulation for CPB. Fifteen patients presented acute type
      A aortic dissection and were operated urgently. Axillary cannulation was also
      used in 11 elective cases: 3 reoperative coronary surgery, 3 valve redo
      operations and 5 cases of aortic valve regurgitation+aneurysm of the ascending
      aorta. RESULTS: All axillary artery cannulations were successful (21 direct and 5
      with a side graft) without neurologic or vascular injuries to the right upper
      extremities. Hospital mortality was 7.7% and included 2 patients operated in an
      emergency procedure because of acute type A aortic dissection. In all cases, this
      cannulation site provided adequate perfusion, with a range of peak flows from 4.1
      to 5.7 L/min. CONCLUSION: Our preliminary results demonstrate that the right
      axillary artery may be considered an alternative cannulation site for achieving
      full CPB and providing antegrade flow, thus avoiding complications related to
      retrograde flow when femoral artery perfusion is performed. This safe and useful
      method may be used not only in aortic surgery but in other such complex cardiac
      procedures as redo-operations.

PMID- 16953167
TI  - The Myocardial Performance Index detects chronic cardiac allograft dysfunction
      sooner than other methods.
AB  - AIM: Many noninvasive techniques have been proposed for the early detection of
      chronic heart graft dysfunction. Diastolic dysfunction may precede systolic
      dysfunction, and often is prominent; therefore, the aim of the study was to
      investigate the clinical and prognostic value of a Doppler-derived index of both
      systolic and diastolic function in heart transplanted patients (Myocardial
      Performance Index, MPI). METHODS: The MPI was measured in 63 consecutive patients
      (mean age 55 years, 49 men and 14 women) in sinus rhythm with an orthotopic heart
      transplantation for at least 1 year (mean 5.3 years) and in 63 age and sex
      matched controls. A complete clinical examination was performed at the time of
      enrollment and was repeated after 3 months. RESULTS: At 3 months, 11 patients
      (17.5%) presented events (heart failure, hospitalisation or cardiac death).
      Patients were divided into 2 groups: Group A (52 patients) without events in the
      follow-up and Group B (11 patients) with events. The values of MPI in Group B
      (0.55+/-0.19) were significantly higher than values in Group A (0.34+/-0.18,
      P=0.001). Whereas the values of the index did not differ significantly between
      Group A and control group (0.34+/-0.18 vs 0.33+/-0.10, P=NS). In the univariate
      analysis, the population of heart transplanted patients was dichotomised in
      subgroups by a cut-off MPI of 0.47 and a cut-off ejection fraction (EF) of 50%.
      Nine patients (41%) with MPI=or>0.47 presented events, while only 2 patients (5%)
      with MPI<0.47 had any event (P<0.001; c2 12.9). Six patients (85%) with EF<50%
      had events, while only 5 patients (9%) with EF=or>50% had an event (P<0.001; c2
      14). In the multivariate analysis only MPI (chi squared=22.6, P=0.018) and EF
      (chi squared=20.8, P=0.025) were significant independent predictors of heart
      failure or cardiac death. By looking at Kaplan-Meyer curves, MPI seems to be
      better than EF in the earlier detection of graft dysfunction. CONCLUSION: MPI, as
      a combined systolic and diastolic index, may detect graft dysfunction earlier
      than EF.

PMID- 16953168
TI  - Results of endocardial radiofrequency ablation of atrial fibrillation during
      mitral valve surgery.
AB  - AIM: The aim of the study is to evaluate the efficacy of thermocontrolled
      endocardial radiofrequency (RF) ablation for the patients with mitral valve
      disorder and associated chronic atrial fibrillation during mitral valve
      replacement operation. METHODS: Between February 2002 and January 2004, 43
      patients with mitral valve disease and associated chronic atrial fibrillation
      underwent mitral valve replacement and thermocontrolled endocardial RF ablation
      with Cobra RF system flexible probe at Gulhane Military Academy of Medicine,
      Department of Cardiovascular Surgery. Eighteen of the patients (41.8%) were
      males, while the remaining 25 (58.2%) were females. The average age of the
      patients was 44+/-14.21 (18-66) years. Functional capacity of the patients was
      class II in 15 (34. 9%), class III in 24 (55.8%), class IV in 4 (9.3%) according
      to the NYHA classification. At the preoperative period all of the patients were
      evaluated routinely by twelve-lead ECG, chest film and transthoracic
      echocardiography (TTE). For the patients over 40 years of age, we performed
      additional coronary angiography to delineate any coronary lesions. The patients
      were evaluated at months 1, 3, 6 and annually by twelve-lead ECG, TTE and holter
      monitoring after discharge. RESULTS: There were not any complications related to
      the performed technique. No operative and hospital mortality were recorded. At
      the follow-up period for 35 of 43 patients (81.4%) sinus rhythm was restored. The
      mean follow-up time was 24.3+/-11.2 (12-35) months. CONCLUSION: Endocardial RF
      ablation especially during mitral valve surgery is a simple technique to be
      performed. Early and midterm results of the cohort are satisfying.

PMID- 16953169
TI  - Complete arterial revascularization in coronary artery bypass grafting in a
      patient with solitus inversus totalis.
AB  - Dextrocardia with complete situs inversus is a rare condition that occurs
      approximately in 2/10,000 live births. Coronary revascularization management in
      this setting differs in the technical considerations imposed by the malposition
      of the heart itself. We report here a case of complete arterial revascularization
      using both internal thoracic arteries and the left (homologous vessel to the
      right) gastroepiploic artery in an adult patient with triple-vessel disease and
      situs inversus totalis. Strategies for the choice of conduits and anastomoses as
      well as technical details are discussed.

PMID- 16953170
TI  - Angiofibroma of the tricuspid valve: a rare presentation of the tuberous
      sclerosis complex?

PMID- 16953171
TI  - Protein expression analysis of Halobacillus dabanensis D-8T subjected to salt
      shock.
AB  - To investigate the mechanism of salt tolerance of gram-positive moderately
      halophilic bacteria, two-dimensional gel electrophoresis (2-D PAGE) was employed
      to achieve high resolution maps of proteins of Halobacillus dabanensis D-8T.
      Approximately 700 spots of proteins were identified from these 2-D PAGE maps. The
      majority of these proteins had molecular weights between 17.5 and 66 kDa, and
      most of them were distributed between the isoelectric points (pI) 4.0 and 5.9.
      Some protein spots were distributed in the more acidic region of the 2-D gel (pI
      <4.0). This pattern indicated that a number of proteins in the strain D-8T are
      acidic. To understand the adaptation mechanisms of moderately halophilic bacteria
      in response to sudden environmental changes, differential protein profiles of
      this strain were investigated by 2-D PAGE and Imagemaster 2D Platinum software
      after the cells were subjected to salt shock of 1 to 25% salinity for 5 and 50
      min. Analysis showed 59 proteins with an altered level of expression as the
      result of the exposure to salt shock. Eighteen proteins had increased expression,
      8 proteins were induced, and the expression of 33 proteins was down-regulated.
      Eight of the up-regulated proteins were identified using MALDI-TOF/MS and MASCOT,
      and were similar to proteins involved in signal transduction, proteins
      participating in energy metabolism pathways and proteins involved in stress.

PMID- 16953172
TI  - Proteomic analysis of protein expression in Streptococcus pneumoniae in response
      to temperature shift.
AB  - From its initial colonization to causation of disease, Streptococcus pneumoniae
      has evolved strategies to cope with a number of stressful in vivo environmental
      conditions. In order to analyze a global view of this organism's response to heat
      shock, we established a 2-D electrophoresis proteome map of the S. pneumoniae D39
      soluble proteins under in vitro culture conditions and performed the comparative
      proteome analysis to a 37 to 42 degrees temperature up-shift in S. pneumoniae.
      When the temperature of an exponentially growing S. pneumoniae D39 culture was
      raised to 42 degrees , the expression level of 25 proteins showed changes when
      compared to the control. Among these 25 proteins, 12 were identified by MALDI-TOF
      and LC-coupled ESI MS/MS. The identified proteins were shown to be involved in
      the general stress response, energy metabolism, nucleotide biosynthesis pathways,
      and purine metabolism. These results provide clues for understanding the
      mechanism of adaptation to heat shock by S. pneumoniae and may facilitate the
      assessment of a possible role for these proteins in the physiology and
      pathogenesis of this pathogen.

PMID- 16953173
TI  - A comparison of the phenotypic and genetic stability of recombinant Trichoderma
      spp. generated by protoplast- and Agrobacterium-mediated transformation.
AB  - Four different Trichoderma strains, T. harzianum CECT 2413, T. asperellum T53, T.
      atroviride T11 and T. longibrachiatum T52, which represent three of the four
      sections contained in this genus, were transformed by two different techniques: a
      protocol based on the isolation of protoplasts and a protocol based on
      Agrobacterium-mediated transformation. Both methods were set up using hygromycin
      B or phleomycin resistance as the selection markers. Using these techniques, we
      obtained phenotypically stable transformants of these four different strains. The
      highest transformation efficiencies were obtained with the T. longibrachiatum T52
      strain: 65-70 transformants/microg DNA when transformed with the plasmid pAN7-1
      (hygromycin B resistance) and 280 transformants/107 spores when the Agrobacterium
      mediated transformation was performed with the plasmid pUR5750 (hygromycin B
      resistance). Overall, the genetic analysis of the transformants showed that some
      of the strains integrated and maintained the transforming DNA in their genome
      throughout the entire transformation and selection process. In other cases, the
      integrated DNA was lost.

PMID- 16953174
TI  - Isolation and characterization of cold-adapted strains producing beta
      galactosidase.
AB  - beta-Galactosidase is extensively employed in the manufacture of dairy products,
      including lactose-reduced milk. Here, we have isolated two gram-negative and rod
      shaped coldadapted bacteria, BS 1 and HS 39. These strains were able to break
      down lactose at low temperatures. Although two isolates were found to grow well
      at 10 degrees , the BS 1 strain was unable to grow at 37 degrees . Another
      strain, HS-39, evidenced retarded growth at 37 degrees . The biochemical
      characteristics and the results of 16S rDNA sequencing identified the BS 1
      isolate as Rahnella aquatilis, and showed that the HS 39 strain belonged to genus
      Buttiauxella. Whereas the R. aquatilis BS 1 strain generated maximal quantities
      of beta-galactosidase when incubated for 60 h at 10 degrees , Buttiauxella sp. HS
      39 generated beta-galactosidase earlier, and at slightly lower levels, than R.
      aquatilis BS 1. The optimum temperature for beta-galactosidase was 30 degrees for
      R. aquatilis BS-1, and was 45 degrees for Buttiauxella sp. HS-39, thereby
      indicating that R. aquatilis BS-1 was able to generate a cold-adaptive enzyme.
      These two cold-adapted strains, and most notably the beta-galactosidase from each
      isolate, might prove useful in some biotechnological applications.

PMID- 16953175
TI  - Rapid detection of noroviruses in fecal samples and shellfish by nucleic acid
      sequence-based amplification.
AB  - The purpose of this study was to determine the efficacy of a nucleic acid
      sequence-based amplification (NASBA) method of detecting noroviruses in
      artificially and naturally contaminated shellfish. We used 58 fecal samples that
      tested positive for noroviruses with electron microscopy (EM) to develop an NASBA
      assay for these viruses. Oligonucleotide primers targeting the polymerase coding
      region were used to amplify the viral RNA in an isothermal process that resulted
      in the accumulation of RNA amplicons. These amplicons were detected by
      hybridization with digoxigenin-labeled oligonucleotide probes that were highly
      specific for genogroup I (GI) and genogroup II (GII) of noroviruses. The expected
      band of 327 bp appeared in denaturing agarose gel without any nonspecific band.
      The specific signal for each amplicon was obtained through Northern blotting in
      many repeats. All fecal samples of which 46 (79.3%) belonged to GII and 12
      (20.6%) belonged to GI were positive for noroviruses by EM and by NASBA. Target
      RNA concentrations as low as 5 pg/ml were detected in fecal specimens using
      NASBA. When the assay was applied to artificially contaminated shellfish, the
      sensitivity to nucleic acid was 100 pg/1.5 g shellfish tissue. The potential use
      of this assay was also confirmed in naturally contaminated shellfish collected
      from different ponds in Guangzhou city of China, of which 24 (18.76%) out of 128
      samples were positive for noroviruses; of these, 19 (79.6%) belonged to GII and 5
      (20.4%) belonged to GI. The NASBA assay provided a more rapid and efficient way
      of detecting noroviruses in fecal samples and demonstrated its potential for
      detecting noroviruses in food and environmental samples with high specificity and
      sensitivity.

PMID- 16953176
TI  - Clarithromycin resistance prevalence and Icea gene status in Helicobacter Pylori
      clinical isolates in Turkish patients with duodenal ulcer and functional
      dyspepsia.
AB  - Clarithromycin resistance in Helicobacter pylori is a principal cause of failure
      of eradication therapies, and its prevalence varies geographically. The IceA gene
      is a virulence factor associated with clinical outcomes. The objective of this
      study was to determine the current state of clarithromycin resistance prevalence,
      and to investigate the role of iceA genotypes in 87 Turkish adult patients (65
      with functional dyspepsia and 22 with duodenal ulcer). A2143G and A2144G point
      mutations were tested by PCR-RFLP for clarithromycin resistance. Among the
      patients in the study, 28 patients were tested by agar dilution as well. Allelic
      variants of the iceA gene were identified by PCR. A total of 24 (27.6%) strains
      evidenced one of the mutations, either A2143G or A2144G. IceA1 was found to be
      positive in 28 of the strains (32.2%), iceA2 was positive in 12 (13.8%) and, both
      iceA1 and iceA2 were positive in 22 (25.3%) strains. In conclusion, we discovered
      no relationships between iceA genotypes and functional dyspepsia or duodenal
      ulcer, nor between clarithromycin resistance and iceA genotypes. Clarithromycin
      resistance appears to be more prevalent in Turkish patients.

PMID- 16953177
TI  - Antibacterial effect of electrolyzed water on oral bacteria.
AB  - This study investigated the antibacterial effect of electrolyzed water on oral
      bacteria both in vitro and in vivo. Tap water was electrolyzed in a water vessel
      using platinum cell technology. The electrolyzed tap water (called Puri-water)
      was put in contact with five major periodontopathogens or toothbrushes
      contaminated with these bacteria for 30 sec. In addition, Puri-water was used as
      a mouthwash for 30 sec in 16 subjects and the antibacterial effect on salivary
      bacteria was evaluated. Puri-water significantly reduced the growth of all
      periodontopathogens in culture and on toothbrushes, and that of aerobic and
      anaerobic bacteria in saliva, when compared to the effect of tap water. It also
      significantly reduced mutans streptococci growing on mitis salivarius-bacitracin
      agar. Our results demonstrate that the electrolyzed tap water is effective as a
      mouthwash and for toothbrush disinfection.

PMID- 16953178
TI  - Outbreaks of imipenem-resistant Acinetobacter baumannii producing carbapenemases
      in Korea.
AB  - Among 53 Acinetobacter baumannii isolates collected in 2004, nine imipenem
      resistant isolates were obtained from clinical specimens taken from patients
      hospitalized in Busan, Korea. Nine carbapenemase-producing isolates were further
      investigated in order to determine the mechanisms underlying resistance. These
      isolates were then analyzed via antibiotic susceptibility testing,
      microbiological tests of carbapenemase activity, pI determination,
      transconjugation test, enterobacterial repetitive consensus (ERIC)-PCR, and DNA
      sequencing. One outbreak involved seven cases of infection by A. baumannii
      producing OXA-23 beta-lactamase, and was found to have been caused by a single
      ERIC-PCR clone. During the study period, the other outbreak involved two cases of
      infection by A. baumannii producing IMP-1 beta-lactamase. The two clones, one
      from each of the outbreaks, were characterized via a modified cloverleaf synergy
      test and an EDTA-disk synergy test. The isoelectric focusing of the crude
      bacterial extracts detected nitrocefin-positive bands with pI values of 6.65 (OXA
      23) and 9.0 (IMP-1). The PCR amplification and characterization of the amplicons
      via direct sequencing showed that the clonal isolates harbored blaIMP-1 or blaOXA
      23 determinants. The two clones were characterized by a multidrug resistance
      phenotype that remained unaltered throughout the outbreak. This resistance
      encompassed penicillins, extended-spectrum cephalosporins, carbapenems,
      monobactams, and aminoglycosides. These results appear to show that the imipenem
      resistance observed among nine Korean A. baumannii isolates could be attributed
      to the spread of an IMP-1- or OXA-23-producing clone. Our microbiological test of
      carbapenemase activity is a simple method for the screening of clinical isolates
      producing class D carbapenemase and/or class B metallo-beta-lactamase, in order
      both to determine their clinical impact and to prevent further spread.

PMID- 16953179
TI  - Meroparamycin production by newly isolated Streptomyces sp. strain MAR01:
      taxonomy, fermentation, purification and structural elucidation.
AB  - Twelve actinomycete strains were isolated from Egyptian soil. The isolated
      actinomycete strains were then screened with regard to their potential to
      generate antibiotics. The most potent of the producer strains was selected and
      identified. The cultural and physiological characteristics of the strain
      identified the strain as a member of the genus Streptomyces. The nucleotide
      sequence of the 16S rRNA gene (1.5 kb) of the most potent strain evidenced a 99%
      similarity with Streptomyces spp. and S. aureofaciens 16S rRNA genes, and the
      isolated strain was ultimately identified as Streptomyces sp. MAR01. The
      extraction of the fermentation broth of this strain resulted in the isolation of
      one major compound, which was active in vitro against gram-positive, gram
      negative representatives and Candida albicans. The chemical structure of this
      bioactive compound was elucidated based on the spectroscopic data obtained from
      the application of MS, IR, UV, 1H NMR, 13C NMR, and elemental analysis
      techniques. Via comparison to the reference data in the relevant literature and
      in the database search, this antibiotic, which had a molecular formula of
      C19H29NO2 and a molecular weight of 303.44, was determined to differ from those
      produced by this genus as well as the available known antibiotics. Therefore,
      this antibiotic was designated Meroparamycin.

PMID- 16953180
TI  - Improved production of live cells of Lactobacillus rhamnosus by continuous
      cultivation using glucose-yeast extract medium.
AB  - In this study, the growth kinetics of Lactobacillus rhamnosus and lactic acid
      production in continuous culture were assessed at a range of dilution rates (0.05
      h(-1) to 0.40 h(-1)) using a 2 L stirred tank fermenter with a working volume of
      600 ml. Unstructured models, predicated on the Monod and Luedeking-Piret
      equations, were employed to simulate the growth of the bacterium, glucose
      consumption, and lactic acid production at different dilution rates in continuous
      cultures. The maximum specific growth rate of L. rhamnosus, mu-max, was estimated
      at 0.40 h(-1), and the Monod cell growth saturation constant, Ks, at
      approximately 0.25 g/L. Maximum cell viability (1.3 x 10(10) CFU/ml) was achieved
      in the dilution rate range of D = 0.28 h(-1) to 0.35 h(-1). Both maximum viable
      cell yield and productivity were achieved at D = 0.35 h(-1). The continuous
      cultivation of L. rhamnosus at D = 0.35 h(-1) resulted in substantial
      improvements in cell productivity, of 267% (viable cell count) that achieved via
      batch cultivation.

PMID- 16953181
TI  - Role of a third extracellular domain of an ecotropic receptor in Moloney murine
      leukemia virus infection.
AB  - The murine ecotropic retroviral receptor has been demonstrated to function as a
      mouse cationic amino acid transporter 1 (mCAT1), and is comprised of multiple
      membranespanning domains. Feral mouse (Mus dunni) cells are not susceptible to
      infection by the ecotropic Moloney murine leukemia virus (MoMLV), although they
      can be infected by other ecotropic murine leukemia viruses, including Friend MLV
      and Rauscher MLV. The relative inability of MoMLV to replicate in M. dunni cells
      has been attributed to two amino acids (V214 and G236) located within the third
      extracellular loop of the M. dunni CAT1 receptor (dCAT1). Via the exchange of the
      third extracellular loop of the mCAT1 cDNA encoding receptor from the permissive
      mouse and the corresponding portion of cDNA encoding for the nonpermissive M.
      dunni receptor, we have identified the most critical amino acid residue, which is
      a glycine located at position 236 within the third extracellular loop of dCAT1.
      We also attempted to determine the role of the third extracellular loop of the M.
      dunni CAT1 receptor with regard to the formation of the syncytium. The
      relationship between dCAT1 and virus-induced syncytia was suggested initially by
      our previous identification of two MLV isolates (S82F in Moloney and S84A in
      Friend MLV), both of which are uniquely cytopathic in M. dunni cells. In an
      attempt to determine the relationship existing between dCAT1 and the virally
      induced syncytia, we infected 293-dCAT1 or chimeric dCAT1 cells with the S82F
      pseudotype virus. The S82F pseudotype virus did not induce the formation of
      syncytia, but did show increased susceptibility to 293 cells expressing dCAT1.
      The results of our study indicate that S82F-induced syncytium formation may be
      the result of cell-cell fusion, but not virus-cell fusion.

PMID- 16953182
TI  - VanB-vanA incongruent VRE isolated from animals and humans in 1999.
AB  - 16 chicken isolates and four clinical isolates of VanB-vanA incongruent
      vancomycinresistant Enterococcus faecium strains without vanS were isolated in
      1999. Pulsed-field gel electrophoresis revealed only a peripheral relationship
      between the chicken isolates and clinical isolates, but suggested clonal spread
      in the chicken isolates.

PMID- 16953183
TI  - Laboratory confirmation of a suspicious meningococcal meningitis death case.
AB  - A suspicious meningococcal meningitis death case was reported to the Beijing CDC.
      The blood specimen was analyzed via multi-PCR and MLST. 6 isolates from close
      contacts were analyzed via PFGE and MLST. According to the results of the above
      analyses, the cause of this case was identified as a serogroup A Neisseria
      meningitidis, which, in terms of sequence typing, belonged the ST7 group.

PMID- 16953184
TI  - Occurrence of thioredoxin reductase in Deinococcus species, the UV resistant
      bacteria.
AB  - The occurrence of thioredoxin reductase (NAD(P)H: oxidized-thioredoxin reductase,
      EC 1.6.4.5, TrxR) in five mesophilic species of Deinococcus was investigated by
      PAGE. Each species possessed a unique TrxR pattern, for example, a single TrxR
      characterized D. radiopugnans while multiple forms of TrxR occurred in other
      Deinococcal spp. Most of TrxRs occurring in Deinococcus showed dual cofactor
      specificity, active with either NADH or NADPH, although the NADPH specific-TrxR
      was observed in D. radiophilus and D.proteolyticus.

PMID- 16953185
TI  - Decomposition of biological macromolecules by plasma generated with helium and
      oxygen.
AB  - In this study, we attempted to characterize the biomolecular effects of an
      atmospheric pressure cold plasma (APCP) system which utilizes helium/oxygen
      (He/O(2)). APCP using He/O(2) generates a low level of UV while generating
      reactive oxygen radicals which probably serve as the primary factor in
      sterilization; these reactive oxygen radicals have the advantage of being capable
      to access the interiors of the structures of microbial cells. The damaging
      effects of plasma exposure on polypeptides, DNA, and enzyme proteins in the cell
      were assessed using biochemical methods.

PMID- 16953186
TI  - In vitro and in vivo pharmacology of synthetic olivetol- or resorcinol-derived
      cannabinoid receptor ligands.
AB  - BACKGROUND AND PURPOSE: We have previously reported the development of CB-25 and
      CB-52, two ligands of CB1 and CB2 cannabinoid receptors. We assessed here their
      functional activity. EXPERIMENTAL APPROACH: The effect of the two compounds on
      forskolin-induced cAMP formation in intact cells or GTP-gamma-S binding to cell
      membranes, and their action on nociception in vivo was determined. KEY RESULTS:
      CB-25 enhanced forskolin-induced cAMP formation in N18TG2 cells (EC50
      approximately 20 nM, max. stimulation = 48%), behaving as an inverse CB1 agonist,
      but it stimulated GTP-gamma-S binding to mouse brain membranes, behaving as a
      partial CB1 agonist (EC50 =100 nM, max. stimulation = 48%). At human CB1
      receptors, CB-25 inhibited cAMP formation in hCB1-CHO cells (EC50 = 1600 nM, max.
      inhibition = 68% of CP-55,940 effect). CB-52 inhibited forskolin-induced cAMP
      formation by N18TG2 cells (IC50 = 450 nM, max. inhibition = 40%) and hCB1-CHO
      cells (EC50 = 2600 nM, max. inhibition = 62% of CP-55,940 effect), and stimulated
      GTP-gamma-S binding to mouse brain membranes (EC50 = 11 nM, max. stimulation
      approximately 16%). Both CB-25 and CB-52 showed no activity in all assays of CB2
      coupled functional activity and antagonized CP55940-induced stimulation of GTP
      gamma-S binding to hCB2-CHO cell membranes. In vivo, both compounds, administered
      i.p., produced dose-dependent nociception in the plantar test carried out in
      healthy rats, and antagonised the anti-nociceptive effect of i.p. WIN55,212-2. In
      the formalin test in mice, however, the compounds counteracted both phases of
      formalin-induced nociception. CONCLUSIONS AND IMPLICATIONS: CB-25 and CB-52
      behave in vitro mostly as CB1 partial agonists and CB2 neutral antagonists,
      whereas their activity in vivo might depend on the tonic activity of cannabinoid
      receptors.

PMID- 16953187
TI  - Opposite diastereoselective activation of P2Y1 and P2Y11 nucleotide receptors by
      adenosine 5'-O-(alpha-boranotriphosphate) analogues.
AB  - BACKGROUND AND PURPOSE: We explored the stereoselective activation of the P2Y11
      receptor, stably expressed and tagged with GFP, in 1321N1 cells, in comparison to
      its closest homologue, the P2Y1 receptor. EXPERIMENTAL APPROACH: The potency of
      several chiral ATP analogues was determined by measuring increases in
      intracellular calcium concentration ([Ca2+]i). In a series of ATP-alpha-B and ATP
      alpha-S analogues, a non-bridging oxygen atom of Palpha was substituted by BH3 or
      sulphur, respectively, introducing a chiral center at Palpha. The pairs of
      diastereoisomers (A and B isomers) were each applied as purified compounds. KEY
      RESULTS: The (B) isomers (ATP-alpha-B Sp isomers and ATP-alpha-S Rp isomers) of
      all derivatives tested were more potent at the P2Y11 receptor than the
      corresponding (A) isomers (ATP-alpha-B Rp isomers and ATP-alpha-S Sp isomers) and
      the parent compounds. This characteristic of the P2Y11 receptor is opposite to
      the behaviour of the same diastereoisomers at the P2Y1 receptor, at which the (A)
      isomers are more active. CONCLUSIONS AND IMPLICATIONS: The distinctly opposite
      diastereoselective activity of ATP derivatives at the P2Y11 and the P2Y1 receptor
      will allow the deciphering of structural differences of the ligand recognition
      sites between these receptor subtypes and may aid in the development of subtype
      selective agonists. Moreover, ATP-alpha-B diastereoisomers are not active at the
      P2Y2 receptor. Thus, they are compounds suitable for distinguishing the
      functional contribution of the two ATP-activated P2Y receptors, the P2Y2 and
      P2Y11 receptor, in physiological or pathophysiological responses of cells.

PMID- 16953188
TI  - Inhibitory effect of p38 mitogen-activated protein kinase inhibitors on cytokine
      release from human macrophages.
AB  - BACKGROUND AND PURPOSE: Macrophages release cytokines that may contribute to
      pulmonary inflammation in conditions such as chronic obstructive pulmonary
      disease. Thus, inhibition of macrophage cytokine production may have therapeutic
      benefit. p38 MAPK may regulate cytokine production, therefore, the effect of two
      p38 MAPK inhibitors, SB239063 and SD-282, on the release of TNF-alpha, GM-CSF and
      IL-8 from human macrophages was investigated. EXPERIMENTAL APPROACH: Cytokine
      release was measured by ELISA. Immunoblots and mRNA expression studies were
      performed to confirm p38 MAPK isoform expression and activity. Macrophages were
      isolated from lung tissue of current smokers, ex-smokers and emphysema patients
      and exposed to lipopolysaccharide. These cells then released cytokines in a
      concentration-dependent manner. KEY RESULTS: SB239063 only inhibited TNF-alpha
      release (EC50 0.3 +/- 0.1 microM). Disease status had no effect on the efficacy
      of SB239063. SD-282 inhibited both TNF-alpha and GM-CSF release from macrophages
      (EC50 6.1 +/- 1.4 nM and 1.8 +/- 0.6 microM respectively) but had no effect on IL
      8 release. In contrast, both inhibitors suppressed cytokine production in
      monocytes. CONCLUSIONS AND IMPLICATIONS: The differential effects of p38 MAPK
      inhibitors between macrophages and monocytes could not be explained by
      differences in p38 MAPK isoform expression or activity. However, the stability of
      TNF-alpha mRNA was significantly increased in macrophages compared to monocytes.
      These data suggest a differential involvement for p38 MAPK in macrophage cytokine
      production compared with monocytes. These effects are not due to lack of p38
      activation or p38alpha expression in macrophages but may reflect differential
      effects on the stability of cytokine mRNA.

PMID- 16953189
TI  - Heme oxygenase/carbon monoxide-biliverdin pathway down regulates neutrophil
      rolling, adhesion and migration in acute inflammation.
AB  - BACKGROUND AND PURPOSE: Heme oxygenase (HO) activity is known to down-regulate
      inflammatory events. Here, we address the role of HO and its metabolites, carbon
      monoxide (CO) and biliverdin (BVD), in leukocyte rolling, adhesion and neutrophil
      migration during inflammatory processes. EXPERIMENTAL APPROACH: Intravital
      microscopy was used to evaluate leukocyte rolling and adhesion in the mesenteric
      microcirculation of mice. TNFalpha and IL-1beta were determined by ELISA and HO-1
      protein expression by Western blot. KEY RESULTS: Intraperitoneal challenge with
      carrageenan enhanced HO-1 protein expression in mesentery and bilirubin
      concentration in peritoneal exudates. Pretreatment of mice with a non-specific
      inhibitor of HO (ZnDPBG) or with a HO-1 specific inhibitor (ZnPP IX) enhanced
      neutrophil migration, rolling and adhesion on endothelium induced by carrageenan.
      In contrast, HO substrate (hemin), CO donor (DMDC) or BVD reduced these
      parameters. The reduction of neutrophil recruitment promoted by HO metabolites
      was independent of the production of chemotactic cytokines. Inhibitory effects of
      CO, but not of BVD, were counteracted by treatment with a soluble guanylate
      cyclase (sGC) inhibitor, ODQ. Furthermore, inhibition of HO prevented the
      inhibitory effect of a nitric oxide (NO) donor (SNAP) upon neutrophil migration,
      while the blockade of NO synthase (NOS) activity by aminoguanidine did not affect
      the CO or BVD effects. CONCLUSIONS AND IMPLICATIONS: Metabolites of HO decreased
      leukocyte rolling, adhesion and neutrophil migration to the inflammatory site by
      a mechanism partially dependent on sGC. Moreover, inhibition by NO of neutrophil
      migration was dependent on HO activity.

PMID- 16953190
TI  - Effects of the somatostatin receptor subtype 4 selective agonist J-2156 on
      sensory neuropeptide release and inflammatory reactions in rodents.
AB  - BACKGROUND AND PURPOSE: Substance P (SP) and calcitonin gene-related peptide
      (CGRP) released from capsaicin-sensitive sensory nerves induce local neurogenic
      inflammation; somatostatin exerts systemic anti-inflammatory actions presumably
      via sst4/sst1 receptors. This study investigates the effects of a high affinity,
      sst4-selective, synthetic agonist, J-2156, on sensory neuropeptide release in
      vitro and inflammatory processes in vivo. EXPERIMENTAL APPROACH: Electrically
      induced SP, CGRP and somatostatin release from isolated rat tracheae was measured
      with radioimmunoassay. Mustard oil-induced neurogenic inflammation in rat hindpaw
      skin was determined by Evans blue leakage and in the mouse ear with micrometry.
      Dextran-, carrageenan- or bradykinin-induced non-neurogenic inflammation was
      examined with plethysmometry or Evans blue, respectively. Adjuvant-induced
      chronic arthritis was assessed by plethysmometry and histological scoring.
      Granulocyte accumulation was determined with myeloperoxidase assay and IL-1beta
      with ELISA. KEY RESULTS: J-2156 (10-2000 nM) diminished electrically-evoked
      neuropeptide release in a concentration-dependent manner. EC50 for the inhibition
      of substance P, CGRP and somatostatin release were 11.6 nM, 14.3 nM and 110.7 nM,
      respectively. J-2156 (1-100 microg kg(-1) i.p.) significantly, but not dose
      dependently, inhibited neurogenic and non-neurogenic acute inflammatory processes
      and adjuvant-induced chronic oedema and arthritic changes. Endotoxin-evoked
      myeloperoxidase activity and IL-1beta production in the lung, but not IL-1beta-
      or zymosan-induced leukocyte accumulation in the skin were significantly
      diminished by J-2156. CONCLUSIONS AND IMPLICATIONS: J-2156 acting on sst4
      receptors inhibits neuropeptide release, vascular components of acute
      inflammatory processes, endotoxin-induced granulocyte accumulation and IL-1beta
      synthesis in the lung and synovial and inflammatory cells in chronic arthritis.
      Therefore it might be a promising lead for the development of novel anti
      inflammatory drugs.

PMID- 16953194
TI  - Writing readable prose: when planning a scientific manuscript, following a few
      simple rules has a large impact.

PMID- 16953191
TI  - An M2-like muscarinic receptor enhances a delayed rectifier K+ current in rat
      sympathetic neurones.
AB  - BACKGROUND AND PURPOSE: Resting superior cervical ganglion (SCG) neurones are
      phasic cells that switch to a tonic mode of firing upon muscarinic receptor
      stimulation. This effect is partially due to the muscarinic inhibition of the M
      current. Because delayed rectifier K+ channels are essential to sustain tonic
      firing in central neurones, we asked whether the delayed rectifier current IKV in
      SCG neurones was modulated by the muscarinic receptors expressed in these cells.
      EXPERIMENTAL APPROACH: Whole-cell patch-clamp records of M-current and IKV were
      done in cultured or acutely dissociated rat SCG neurones. To characterize the
      receptor that regulates IKV, cells were bathed with muscarinic agonists and
      antagonists, relatively specific for receptor subtypes. KEY RESULTS: The
      muscarinic agonist oxotremorine-M (Oxo-M) enhanced IKV by approximately 46%
      relative to its basal value. This effect remained unaltered when M-current was
      suppressed by linopirdine or Ba2+. Enhancement of IKV was insensitive to the M1
      antagonist pirenzepine, whereas it was inhibited (approximately 60%) by the M2/4
      antagonist himbacine. Further, the relatively specific M2-agonist bethanechol was
      as potent as Oxo-M in enhancing IKV. The modulation of IKV was insensitive to
      pertussis toxin (PTX), but was severely attenuated when internal ATP was replaced
      by its non-hydrolysable analogue AMP-PNP. CONCLUSIONS AND IMPLICATIONS: These
      results suggest that an M2-like muscarinic receptor couples to a PTX-insensitive
      G-protein and to an ATP-dependent pathway to enhance IKV. Modulation of IKV must
      be taken into consideration in order to understand more precisely how muscarinic
      receptors acting on different ion channels regulate sympathetic excitability.

PMID- 16953192
TI  - Co-administration of pentoxifylline and thiopental causes death by acute
      pulmonary oedema in rats.
AB  - BACKGROUND AND PURPOSE: Pentoxifylline exhibits rheological properties that
      improve microvascular flow and it is widely used in vascular perfusion disorders.
      It also exhibits marked anti-inflammatory properties by inhibiting tumour
      necrosis factor alpha production. Thiopental is one of the most widely used drugs
      for rapid induction of anaesthesia. During experimental studies on the treatment
      of acute pancreatitis, we observed that when pentoxifylline was administered
      after anaesthesia with thiopental, most of the rats exhibited dyspnea, signs of
      pulmonary oedema and died. The aim of the work described here was to investigate
      the cause of the unexpected toxic effect of the combined treatment with
      thiopental and pentoxifylline. EXPERIMENTAL APPROACH: Pulmonary vascular
      permeability and arterial blood gases were measured, and a histological analysis
      was performed. The possible role of haemodynamic changes in the formation of
      pulmonary oedema was also assessed. KEY RESULTS: Co-administration of
      pentoxifylline and thiopental increased pulmonary vascular permeability and
      markedly decreased arterial pO2, with one third of rats suffering from hypoxemia.
      This combined treatment caused death by acute pulmonary oedema in 27% of normal
      rats and aggravated the respiratory insufficiency associated with acute
      pancreatitis in which the mortality rate increased to 60%. This pulmonary oedema
      was not mediated by cardiac failure or by pulmonary hypertension. CONCLUSIONS AND
      IMPLICATIONS: Co-administration of pharmacological doses of pentoxifylline and
      thiopental caused pulmonary oedema and death in rats. Consequently,
      pentoxifylline should not be administered when anaesthesia is induced with
      thiopental to avoid any possible risk of acute pulmonary oedema and death in
      humans.

PMID- 16953195
TI  - Bioethics in China: although national guidelines are in place, their
      implementation remains difficult.

PMID- 16953196
TI  - Tracking the spread of infectious disease: two networks prove the power of
      international collaboration.

PMID- 16953197
TI  - Nanoregulation: a recent scare involving nanotech products reveals that the
      technology is not yet properly regulated.

PMID- 16953198
TI  - Entente cordiale: multiple symbiosis illustrates the intricate interconnectivity
      of nature.

PMID- 16953200
TI  - Organellar proteomics: turning inventories into insights.
AB  - Subcellular organization is yielding to large-scale analysis. Researchers are now
      applying robust mass-spectrometry-based proteomics methods to obtain an inventory
      of biochemically isolated organelles that contain hundreds of proteins. High
      resolution methods allow accurate protein identification, and novel algorithms
      can distinguish genuine from co-purifying components. Organellar proteomes have
      been analysed by bioinformatic methods and integrated with other large-scale data
      sets. The dynamics of organelles can also be studied by quantitative proteomics,
      which offers powerful methods that are complementary to fluorescence-based
      microscopy. Here, we review the emerging trends in this rapidly expanding area
      and discuss the role of organellar proteomics in the context of functional
      genomics and systems biology.

PMID- 16953201
TI  - Mediators of endoplasmic reticulum stress-induced apoptosis.
AB  - The efficient functioning of the endoplasmic reticulum (ER) is essential for most
      cellular activities and survival. Conditions that interfere with ER function lead
      to the accumulation and aggregation of unfolded proteins. ER transmembrane
      receptors detect the onset of ER stress and initiate the unfolded protein
      response (UPR) to restore normal ER function. If the stress is prolonged, or the
      adaptive response fails, apoptotic cell death ensues. Many studies have focused
      on how this failure initiates apoptosis, as ER stress-induced apoptosis is
      implicated in the pathophysiology of several neurodegenerative and cardiovascular
      diseases. In this review, we examine the role of the molecules that are activated
      during the UPR in order to identify the molecular switch from the adaptive phase
      to apoptosis. We discuss how the activation of these molecules leads to the
      commitment of death and the mechanisms that are responsible for the final demise
      of the cell.

PMID- 16953203
TI  - Cryotherapy for the prevention of high-dose melphalan-induced oral mucositis.

PMID- 16953202
TI  - Inside the brain of a neuron.
AB  - For many decades, neurons were considered to be the elementary computational
      units of the brain and were assumed to summate incoming signals and elicit action
      potentials only in response to suprathreshold stimuli. Although modelling studies
      predicted that single neurons constitute a much more powerful computational
      entity, able to perform an array of nonlinear calculations, this possibility was
      not explored experimentally until the discovery of active mechanisms in the
      dendrites of most neuron types. Here, we review several modelling studies that
      have addressed information processing in single neurons, starting with those
      characterizing the arithmetic of different dendritic components, to those
      tackling neuronal integration at the cell body and, finally, those analysing the
      computational abilities of the axon. We present modelling predictions along with
      supporting experimental data in an effort to highlight the significant
      contribution of modelling work to enhancing our understanding of single-neuron
      arithmetic.

PMID- 16953204
TI  - Unrelated bone marrow transplantation using a reduced-intensity conditioning
      regimen for the treatment of Kostmann syndrome.

PMID- 16953205
TI  - Successful cord blood transplantation for myelodysplastic syndrome resulting in
      resolution of pulmonary alveolar proteinosis.

PMID- 16953206
TI  - Oral beclomethasone dipropionate as an initial treatment of gastrointestinal
      acute graft-versus-host disease after reduced-intensity cord blood
      transplantation.

PMID- 16953207
TI  - Individual patient data meta-analysis of allogeneic peripheral blood stem cell
      transplant vs bone marrow transplant in the management of hematological
      malignancies: indirect assessment of the effect of day 11 methotrexate
      administration.
AB  - The effects of immunosuppressive regimens on the outcomes of patients with
      hematological malignancies undergoing allogeneic stem cell transplantation remain
      uncertain. We conducted an individual patient data meta-analysis using data from
      nine randomized trials comparing allogeneic peripheral blood stem cell (PBSCT)
      transplants to bone marrow (BMT) transplants, focusing on the administration of
      three vs four doses of methotrexate (MTX) as part of a regimen for graft-versus
      host-disease (GVHD) prophylaxis which included cyclosporine. Six trials
      containing 573 patients prescribed four doses of MTX while three trials
      containing 534 patients prescribed three doses of MTX. Four doses of MTX
      conferred a statistically significant survival advantage, resulting in death odds
      ratio (OR) 0.67 (CI 0.52-0.88) (P=0.0036) for recipients of PBSC compared to BM;
      with three doses, there was no statistically significant difference. In the four
      dose studies relapse rates were 36.6% among recipients of BM compared to 19.2%
      among recipients of PBSC (P=0.0015). The rates of relapse in the three dose
      studies were 26% for both PBSC and BM. We hypothesize that the fourth dose of MTX
      provides extra immunosuppression among BM recipients resulting in a reduced anti
      leukemic effect. This hypothesis can only be proved or disproved by a
      prospective, randomized trial.

PMID- 16953208
TI  - Female genital tract graft-versus-host disease: incidence, risk factors and
      recommendations for management.
AB  - Female genital tract graft-versus-host disease (GVHD) is an under-recognized
      complication of allogeneic stem cell transplantation impacting on quality of
      life. We describe a prospective surveillance programme for female genital GVHD to
      better characterize incidence, risk factors and clinical features and the impact
      of a structured intervention policy. A retrospective audit was conducted on the
      medical records of all female transplant recipients surviving at least 6 months
      at a single centre over a 5-year period. Patients commenced topical vaginal
      oestrogen early post transplant with hormone replacement as appropriate for age,
      prior menopausal status and co-morbidities. A genital tract management programme
      included regular gynaecological review and self-maintenance of vaginal capacity
      by dilator or intercourse. The incidence of genital GVHD was 35% (95% confidence
      interval (CI) (25, 50%)) at 1 year and 49% (95% CI (36, 63%)) at 2 years. Topical
      therapy was effective in most cases; no patient required surgical intervention to
      divide vaginal adhesions. The main risk factor was stem cell source with
      peripheral blood progenitor cells posing a higher risk than marrow (hazard
      ratio=3.07 (1.22, 7.73), P=0.017). Extensive GVHD in other organs was a common
      association. We conclude that female genital GVHD is common, and early detection
      and commencement of topical immunosuppression with dilator use appears to be
      highly effective at preventing progression.

PMID- 16953209
TI  - Autologous transplantation in elderly patients with multiple myeloma: are we
      asking the right questions?
AB  - Multiple myeloma is a disease of the elderly. Survival outcomes remain
      unacceptably low in older adults with multiple myeloma. To date, no obvious
      difference in tumor biology has been elucidated to explain the survival disparity
      between older and younger patients. Multiple factors including comorbidity,
      performance status, decreased physiologic reserve and potentially undertreatment
      contribute to poor outcomes in elderly patients with multiple myeloma. High-dose
      chemotherapy with autologous stem cell transplantation (ASCT) is increasingly
      being used to treat elderly patients with multiple myeloma in an effort to
      improve survival outcomes. Recent case comparison studies, and preliminary
      transplant registry data suggest that selected older patients can be treated with
      high-dose chemotherapy effectively with similar toxicity and survival benefits
      compared to younger patients. Traditional upper age limits for autologous
      transplantation are being challenged along with the definition of 'elderly'
      itself. Ultimately, the role of high-dose chemotherapy with stem cell rescue in
      the upfront treatment of older adults with multiple myeloma can only be
      established by prospective randomized trials. In the process of designing studies
      to investigate the use of ASCT in older patients, multiple issues unique to the
      elderly population will need to be considered. First, it will be critical to
      develop and validate patient selection algorithms that incorporate measures of
      comorbidity, cognitive function, physiologic reserve and psychosocial function to
      identify patients most likely to tolerate and benefit from ASCT. Second,
      preparative and conditioning regimens will need to be further tailored to
      maximize the benefit to risk ratio. Finally, outcome measures in clinical trials
      should include disability and quality of life measures, which may be equally
      important in making treatment decisions for older patients. The future
      application and study of autologous transplantation in older patients with
      multiple myeloma provides a unique opportunity to challenge ageism and serve as a
      model for development of tailored assessments and interventions in this
      population.

PMID- 16953210
TI  - Stem cell transplantation in children with infantile osteopetrosis is associated
      with a high incidence of VOD, which could be prevented with defibrotide.
AB  - Malignant infantile osteopetrosis (MIOP) is a rare hereditary disorder of
      osteoclast function, which can be reversed by hematopoietic stem cell
      transplantation (SCT). We observed a high incidence of hepatic veno-occlusive
      disease (VOD) in transplanted patients and explored the prevention of this
      complication by using defibrotide (DF) as a prophylaxis. Twenty children with
      MIOP were consecutively transplanted in our center between 1996 and 2005. Eleven
      of these patients were transplanted between 1996 and 2001 and experienced an
      overall incidence of VOD of 63.6% (7/11). VOD was severe in three patients and
      one patient succumbed to VOD-related multi-organ failure. Owing to this very high
      incidence of VOD, DF prophylaxis was initiated in nine patients consecutively
      transplanted between 2001 and 2005. In this group, only one patient (11.1%) was
      diagnosed with moderate VOD. We report here a very high risk in patients with
      MIOP to develop VOD after transplantation. Prophylactic DF was implemented in our
      current transplant protocol and reduced the VOD rate significantly in this high
      risk population.

PMID- 16953211
TI  - Pulmonary complications after T-cell-depleted allogeneic stem cell
      transplantation: low incidence and strong association with acute graft-versus
      host disease.
AB  - Lung injury limits the success of allogeneic stem cell transplantation (SCT). The
      overall incidence varies from 30 to 50% and non-infectious causes occur in one
      third to one-half of these. We reviewed pulmonary complications in 369
      consecutive patients who received a partially T-cell-depleted myeloablative
      allogeneic hematopoietic SCT at our institution between 1993 and 2003. All
      patients were treated uniformly with cyclophosphamide followed by total body
      irradiation. Control subjects were matched on sex, underlying diagnosis, age,
      type of transplantation and cytomegalovirus (CMV)-serostatus. Sixty-one patients
      (16.5%) developed pulmonary complications. Twenty-one patients (5.7%) developed
      infectious pneumonia. Forty patients developed non-infectious complications which
      were further subclassified as bronchiolitis obliterans (3.5%), bronchiolitis
      obliterans-organizing pneumonia (0.5%), diffuse alveolar hemorrhage (0.8%),
      idiopathic pneumonia syndrome (5.5%) or mixed etiology (0.5%). Acute graft-versus
      host disease (GVHD) > or =grade II was significantly more common in pulmonary
      patients than in the controls (36/61 versus 22/61 patients, P=0.02). There was no
      significant difference in the incidence of chronic GVHD (P=0.09). CMV
      reactivation was significantly more frequent in patients with lung injury
      (P=0.02). Median survival was 41 weeks for the pulmonary patients and 350 weeks
      for the controls (P=0.001). Altogether, the incidence of pulmonary complications
      is low after T-cell-depleted SCT and is associated with acute GVHD and CMV
      reactivation.

PMID- 16953212
TI  - Transformed essential thrombocytosis with a JAK2 V617F mutation relapsing as JAK2
      mutation-negative leukaemia after allogeneic stem cell transplantation.

PMID- 16953213
TI  - The second international meeting on allogeneic transplantation in solid tumors.
AB  - In October 2005, the second international meeting on allogeneic transplantation
      in solid tumors was convened in Stresa (Italy). The aim of this second meeting
      was to share clinical experiences of allografting in solid tumors, to discuss
      preclinical data on the mechanisms of graft-versus-tumor (GVT) effect, and to
      review methods for more efficacious transplant approaches. On the first day, the
      most recent results in cancer immunotherapy were reviewed; head-to head
      comparisons of clinical results achieved by standard therapy and by allografting
      in renal, breast, and ovarian cancer were presented. On the second day, GVT
      mechanisms and preclinical models were examined; anecdotal reports of a GVT
      effect in sarcoma, pancreatic cancer, prostate cancer, colorectal cancer and lung
      cancer were presented; new strategies for optimizing transplant outcome were
      discussed, including patient selection, tumor debulking, auto-allo approaches,
      selective T-cell depletion, targeting with monoclonal antibodies, use of killer
      cell immunoglobulin-like receptor-ligand mismatched natural killer cells. In
      conclusion, allografting in solid tumors is feasible with limited toxicities and
      transplant-related mortality; a GVT effect has been documented in many different
      solid tumors; targeting of the immune response to the tumor by new strategies and
      identification of the target antigen(s) of the GVT effect are promising areas of
      research.

PMID- 16953214
TI  - MBL2 polymorphism and risk of severe infections in multiple myeloma patients
      receiving high-dose melphalan and autologous stem cell transplantation.
AB  - Severe infections related to treatment are common in patients with multiple
      myeloma (MM). Genetic polymorphisms of the immune system may influence the risk
      of infections. Mannan-binding lectin (MBL) is part of the innate immune system,
      and individuals homozygous for wild-type MBL encoding gene (MBL2) have a well
      functioning MBL pathway of complement activation, in contrast to individuals
      carrying one or two variant alleles. We evaluated 113 courses of high-dose
      melphalan and autologous stem cell transplantation (ASCT) in patients with MM.
      Patients homozygous for wild-type MBL2 had a significantly reduced risk of
      septicaemia during the ASCT procedure compared with patients carrying variant
      MBL2: Odds Ratio (OR) 0.19 (95% CI: 0.04-0.77), (P=0.02) in multivariate
      analysis. The risk of Common Toxicity Criteria grade 3-4 infections in general
      was not affected by wild-type MBL2: OR 1.20 (95% CI: 0.52-2.78), (P=0.67). The
      findings indicate that MBL to some extent protects against the most severe
      infections during ASCT.

PMID- 16953215
TI  - Xenopus Tbx6 mediates posterior patterning via activation of Wnt and FGF
      signalling.
AB  - In vertebrates, the patterning of anterior-posterior (AP) axis is a fundamental
      process during embryogenesis. Wnt and FGF signalling pathways play important
      roles in regulating the patterning of embryo AP axis. Mouse Tbx6 encodes a
      transcription factor that has been demonstrated to be involved in the
      specification of the posterior tissue in mouse embryonic body. Here, we prove
      that morpholino-induced knockdown of XTbx6 impairs posterior development,
      indicating the requirement of XTbx6 in this process. Meanwhile, gain of XTbx6
      function is sufficient to induce ectopic posterior structures in Xenopus embryos.
      Furthermore, XTbx6 activates the expression of Xwnt8 and FGF8, which are two
      mediators of posterior development, suggesting a mechanism by which XTbx6
      modulates posterior patterning via Wnt and FGF signalling pathway activation.

PMID- 16953216
TI  - Transcription of the putative tumor suppressor gene HCCS1 requires binding of ETS
      2 to its consensus near the transcription start site.
AB  - The hepatocellular carcinoma suppressor 1 (HCCS1) gene was identified by both
      positional cloning from a predominant region of loss of heterozygosity (17p13.3)
      in liver cancer and by functional screening for genes affecting cell
      proliferation in large-scale transfection assays. Its overexpression results in
      inhibition of cell proliferation in cell culture and tumor growth in nude mice.
      To understand its transcription regulation, the promoter architecture has been
      dissected in detail. The major start of transcription was mapped by primer
      extension to a C residue, 177 nucleotides upstream of the ATG codon. By assessing
      the promoter activity of a set of linker-scanning mutants of the minimal promoter
      (-60 to +148 region) in a transient transfection assay, we found that the +1 to +
      40 region is critical to HCCS1 gene transcription, containing binding sites for
      transcription factors NF-kappaB (-21 to +7 and +40 to +26), p53 (+29 to +9) and
      ETS (+4 to +20 and +23 to +39). Biochemical and molecular analyses revealed that
      the ETS transcription factors ETS-2 and Elf-1 bind to the two ETS sites in situ
      and contribute significantly to the transcriptionally active state of the HCCS1
      gene, while NF-kappaB, p53 and two other members of the ETS family (ETS-1 and
      NERF2) appear to play little role. Our observations provide insight into the
      mechanistic aspects of HCCS1 transcription regulation.

PMID- 16953217
TI  - RIZ1 repression is associated with insulin-like growth factor-1 signaling
      activation in chronic myeloid leukemia cell lines.
AB  - RIZ1 is a histone methyltransferase whose expression and activity are reduced in
      many cancers. In chronic myelogenous leukemia (CML), blastic transformation is
      associated with loss of heterozygosity in the region where RIZ1 is located and
      with decreased RIZ1 expression. Forced RIZ1 expression in model CML blast crisis
      (BC) cell lines decreases proliferation, increases apoptosis and enhances
      differentiation. We characterized molecular mechanisms that may contribute to
      potential CML tumor suppressor properties of RIZ1. Several RIZ1-regulated genes
      involved in insulin-like growth factor-1 (IGF-1) signaling were identified using
      cDNA microarrays. RIZ1 was shown to associate with promoter regions of IGF-1 and
      to increase histone H3 lysine 9 methylation using chromatin immunoprecipitation
      assays. IGF-1-blocking antibody was used to demonstrate the importance of
      autocrine IGF-1 signaling in CML-BC cell line viability. Forced RIZ1 expression
      in CML-BC cell lines decreases IGF-1 receptor activation and activation of
      downstream signaling components extracellular signal-regulated kinase 1/2 and
      AKT. These results highlight the therapeutic potential of inhibiting IGF-1
      pathway in the acute phase of CML.

PMID- 16953218
TI  - EGF-independent activation of cell-surface EGF receptors harboring mutations
      found in gefitinib-sensitive lung cancer.
AB  - Several somatic mutations within the tyrosine kinase domain of epidermal growth
      factor receptor (EGFR) have been identified that predict clinical response of non
      small-cell lung carcinoma (NSCLC) patients to gefitinib. To test the hypothesis
      that these mutations cause constitutive EGF receptor signaling, and to
      investigate its mechanistic basis, we expressed representative examples in a null
      background and analysed their biochemical properties. Each mutation caused
      significant EGF-independent tyrosine phosphorylation of EGFR, and allowed the
      receptor to promote Ba/F3 cell mitogenesis in the absence of EGF, arguing that
      these are oncogenic mutations. Active mutated receptors are present at the cell
      surface and are fully competent to bind EGF. Recent structural studies show that
      the inactive EGFR tyrosine kinase domain is autoinhibited by intramolecular
      interactions between its activation loop and alphaC helix. We find that mutations
      predicted to disrupt this autoinhibitory interaction (including several that have
      not been described in NSCLC) elevate EGF-independent tyrosine kinase activity,
      thus providing new insight into how somatic mutations activate EGFR and other
      ErbB family members.

PMID- 16953219
TI  - Transgenic overexpression of IGF-IR disrupts mammary ductal morphogenesis and
      induces tumor formation.
AB  - Overexpression and hyperactivation of the type I insulin-like growth factor
      receptor (IGF-IR) has been observed in human breast tumor biopsies. In addition,
      in vitro studies indicate that overexpression of IGF-IR is sufficient to
      transform cells such as mouse embryo fibroblasts and this receptor promotes
      proliferation and survival in breast cancer cell lines. To fully understand the
      function of the IGF-IR in tumor initiation and progression, transgenic mice
      containing human IGF-IR under a doxycycline-inducible MMTV promoter system were
      generated. Administration of 2 mg/ml doxycycline in the animals' water supply
      beginning at 21 days of age resulted in elevated levels of IGF-IR in mammary
      epithelial cells as detected by Western blotting and immunohistochemistry. Whole
      mount analysis of 55-day-old mouse mammary glands revealed that IGF-IR
      overexpression significantly impaired ductal elongation. Moreover, histological
      analyses revealed multiple hyperplasic lesions in the mammary glands of these 55
      day-old mice. The formation of palpable mammary tumors was evident at
      approximately 2 months of age and was associated with increased levels of IGF-IR
      signaling molecules including phosphorylated Akt, Erk1/Erk2 and STAT3. Therefore,
      these transgenic mice provide evidence that IGF-IR overexpression is sufficient
      to induce mammary epithelial hyperplasia and tumor formation in vivo and provide
      a model to further understand the function of IGF-IR in mammary epithelial
      transformation.

PMID- 16953220
TI  - The p53 knowledgebase: an integrated information resource for p53 research.
AB  - The p53 tumor suppressor protein plays a central role in maintaining genomic
      integrity by occupying a nodal point in the DNA damage control pathway. Here it
      integrates a wide variety of signals, responding in one of several ways, that is,
      cell cycle arrest, senescence or programmed cell death (apoptosis). Mutations in
      the tumor suppressor gene tp53, which affects the key transcriptional regulatory
      processes in cell growth and death, occur frequently in cancer and helps explain
      why p53 has been called the guardian of the genome. There is a vast body of
      published knowledge on all aspects of p53's role in cancer. To facilitate
      research, it would be helpful if this information could be collected, curated and
      updated in a format that is easily accessible to the user community. To this end,
      we initiated the p53 knowledgebase project (http://p53.bii.a-star.edu.sg). The
      p53 knowledgebase is a user-friendly web portal incorporating visualization and
      analysis tools that integrates information from the published literature with
      other manually curated information to facilitate knowledge discovery. This
      includes curated information on sequence, structural, mutation, polymorphisms,
      protein-protein interactions, transcription factors, transcriptional targets,
      antibodies and post-translational modifications that involve p53. The goal is to
      collect and maintain all relevant data on p53 and present it in an easily
      accessible format that will be useful to researchers in the field.

PMID- 16953221
TI  - Dysfunctional AMPK activity, signalling through mTOR and survival in response to
      energetic stress in LKB1-deficient lung cancer.
AB  - LKB1, mutated in Peutz-Jeghers and in sporadic lung tumours, phosphorylates a
      group of protein kinases named AMP-activated protein kinase (AMPK)-related
      kinases. Among them is included the AMPK, a sensor of cellular energy status. To
      investigate the relevance of LKB1 in lung carcinogenesis, we study several lung
      cancer cells with and without LKB1-inactivating mutations. We report that LKB1
      mutant cells are deficient for AMPK activity and refractory to mTOR inhibition
      upon glucose depletion but not growth-factor deprivation. The requirement for
      wild-type LKB1 to properly activate AMPK is further demonstrated in genetically
      modified cancer cells. In addition, LKB1-deficient lung primary tumours had
      diminished AMPK activity, assessed by complete absence or low level of
      phosphorylation of its critical substrate, acetyl-CoA carboxylase. We also
      demonstrate that LKB1 wild-type cells are more resistant to cell death upon
      glucose withdrawal than their mutant counterparts. Finally, modulation of AMPK
      activity did not affect PI3K/AKT signalling, an advantage for the potential use
      of AMPK as a target for cancer therapy in LKB1 wild-type tumours. Thus, sustained
      abrogation of cell energetic checkpoint control, through alterations at key
      genes, appear to be an obligatory step in the development of some lung tumours.

PMID- 16953222
TI  - The Src tyrosine kinase Hck is required for Tel-Abl- but not for Tel-Jak2-induced
      cell transformation.
AB  - Tel-Abl and Tel-Jak2 are fusion proteins associated with human haematologic
      neoplasms. They possess constitutive tyrosine kinase activity and activate common
      downstream signalling pathways like Stat-5, PI3-K/Akt, Ras/MapK and NF-kappaB. In
      this study, we showed the specific requirement of Src family members for the Tel
      Abl-mediated cell growth, activation of Stat5, PI3-K/Akt and Ras/MapK while
      dispensable for Tel-Jak2. Hck was found strongly phosphorylated in Tel-Abl
      expressing Ba/F3 cells and sensitive to imatinib mesylate treatment, providing
      evidence that Hck is a target of Tel-Abl tyrosine kinase activity. Overexpression
      of a kinase dead form of Hck inhibits the proliferation of Ba/F3 cells expressing
      Tel-Abl as the phosphorylation of Akt and Erk1/2. These results argue for an
      important role of Hck in Tel-Abl oncogenic signalling.

PMID- 16953223
TI  - E2F3 is the main target gene of the 6p22 amplicon with high specificity for human
      bladder cancer.
AB  - Amplification of 6p22 occurs in about 10-20% of bladder cancers and is associated
      with enhanced tumour cell proliferation. Candidate target genes for the 6p22
      amplicon include E2F3 and the adjacent gene NM_017774. To clarify which gene is
      representing the main target, we compared the prevalence of the amplification and
      the functional role of both genes. Amplification of E2F3 and NM_017774 was
      analysed by fluorescence in situ hybridization on a bladder cancer tissue
      microarray composed of 2317 cancer samples. Both genes showed amplification in
      104 of 893 (11.6%) interpretable tumours and were exclusively found co-amplified.
      Additional gene expression analysis by real-time polymerase chain reaction in 12
      tumour-derived cell lines revealed that amplification of 6p22 was always
      associated with co-overexpression of E2F3 and NM_017774. Furthermore, RNA
      interference was used to study the influence of reduced gene expression on cell
      growth. In tumour cells with and without the 6p22 amplicon, knockdown of E2F3
      always lead to unequivocal reduction of proliferation, whereas knockdown of
      NM_017774 was only capable to slow down cell proliferation in non-amplified
      cells. Our findings point out that E2F3 but not NM_017774 is driving enhanced
      proliferation of 6p22 amplified tumour cells. We conclude that E2F3 must be
      responsible for the growth advantage of 6p22 amplified bladder cancer cells.

PMID- 16953224
TI  - Evidence that TNF-TNFR1-TRADD-TRAF2-RIP-TAK1-IKK pathway mediates constitutive NF
      kappaB activation and proliferation in human head and neck squamous cell
      carcinoma.
AB  - Constitutively activated nuclear factor-kappaB (NF-kappaB) has been associated
      with a variety of aggressive tumor types, including head and neck squamous cell
      carcinoma (HNSCC); however, the mechanism of its activation is not fully
      understood. Therefore, we investigated the molecular pathway that mediates
      constitutive activation of NF-kappaB in a series of HNSCC cell lines. We
      confirmed that NF-kappaB was constitutively active in all HNSCC cell lines (FaDu,
      LICR-LON-HN5 and SCC4) examined as indicated by DNA binding, immunocytochemical
      localization of p65, by NF-kappaB-dependent reporter gene expression and its
      inhibition by dominant-negative (DN)-inhibitory subunit of NF-kappaB
      (IkappaBalpha), the natural inhibitor of NF-kappaB. Constitutive NF-kappaB
      activation in HNSCC was found to be due to constitutive activation of
      IkappaBalpha kinase (IKK); and this correlated with constitutive expression of
      phosphorylated forms of IkappaBalpha and p65 proteins. All HNSCC showed the
      expression of p50, p52, p100 and receptor-interacting protein; all linked with NF
      kappaB activation. The expression of constitutively active NF-kappaB in HNSCC is
      mediated through the tumor necrosis factor (TNF) signaling pathway, as NF-kappaB
      reporter activity was inhibited by DN-TNF receptor-associated death domain
      (TRADD), DN-TNF receptor-associated factor (TRAF)2, DN-receptor-interacting
      protein (RIP), DN-transforming growth factor-beta-activated kinase 1 (TAK1), DN
      kappa-Ras, DN-AKT and DN-IKK but not by DN-TRAF5 or DN-TRAF6. Constitutive NF
      kappaB activation was also associated with the autocrine expression of TNF, TNF
      receptors and receptor-activator of NF-kappaB and its ligand in HNSCC cells but
      not interleukin (IL)-1beta. All HNSCC cell lines expressed IL-6, a NF-kappaB
      regulated gene product. Furthermore, treatment of HNSCC cells with anti-TNF
      antibody downregulated constitutively active NF-kappaB, and this was associated
      with inhibition of IL-6 expression and cell proliferation. Our results clearly
      demonstrate that constitutive activation of NF-kappaB is mediated through the
      TRADD-TRAF2-RIP-TAK1-IKK pathway, making TNF a novel target in the treatment of
      head and neck cancer.

PMID- 16953225
TI  - Juvenile syndecan-1 null mice are protected from carcinogen-induced tumor
      development.
AB  - We previously showed that mice with a null mutation in syndecan-1 (Sdc1; CD138)
      were resistant to Wnt1-induced mammary tumor initiation. The absence of Sdc1
      inhibited the increase in the mammary stem cell fraction that is characteristic
      of preneoplasia in this model. As the tumor precursor cells are recruited from
      the stem/progenitor cell compartment, tumor development was also inhibited (Liu
      et al., 2004; PNAS 101, 4158). Although Sdc1-/- mice are grossly normal, they are
      systemically smaller, suggesting that developmental abnormalities may extend
      further than their mammary glands. We have therefore evaluated the multi-organ
      response of Sdc1-/- mice to carcinogen-induced tumor development (7,12
      dimethylbenz[a]anthracene, DMBA), and find these mice to be resistant to
      tumorigenesis in all the predominant carcinogen-susceptible lineages. Thus, Sdc1
      /- mice administered DMBA during juvenile development are resistant not only to
      epithelial tumors, including liver (60-80%) and lung tumors (C57BL6 mice, 60
      80%), but also to lymphoma (over 70%, depending upon strain and carcinogen dose).
      We demonstrate that CD138 is expressed (heterogeneously) in the hematopoietic
      stem cell fraction (and not only in pre-B and plasma cells), and that tumors
      arise in both myeloid and lymphoid lineages. Furthermore, carcinogen-induced
      mammary tumors are bilineal, implying a bipotent precursor cell. Both
      observations imply that the DMBA-induced tumor precursor cells are drawn from the
      stem/progenitor fraction, and we suggest that pathogenic activation of these
      cells could be abnormal in Sdc1-/- mice.

PMID- 16953226
TI  - Telomeric aggregates and end-to-end chromosomal fusions require myc box II.
AB  - Telomeres of tumor cells form telomeric aggregates (TAs) within the three
      dimensional (3D) interphase nucleus. Some of these TAs represent end-to-end
      chromosomal fusions and may subsequently initiate breakage-bridge-fusion cycles.
      Wild-type (wt) and myc box II mutant (mt) Myc induce different types of genomic
      instability when conditionally expressed in mouse proB cells (Ba/F3). Only wt Myc
      overexpressing Ba/F3 cells are capable of tumor formation in severe combined
      immunodeficient mice. In this study, we investigated whether telomere dysfunction
      leading to TA formation is linked to the genetic changes that permit wt c-Myc
      dependent transformation of Ba/F3 cells. To this end, we examined the 3D
      organization of telomeres after the deregulated expression of deletion myc boxII
      mutant (Delta106) or wt Myc. Delta106-Myc overexpression did not induce TAs,
      whereas wt-Myc deregulation did. Instead, Delta106-Myc remodelled the 3D
      telomeric organization such that telomeres aligned in the center of the 3D
      interphase nucleus forming a telomeric disk owing to a Delta106-induced G1/S cell
      cycle arrest. In contrast, wt-Myc overexpression led to distorted telomere
      distribution and TA formation. Analysis of chromosomal alterations using spectral
      karyotyping confirmed Delta106-Myc and wt-Myc-associated genomic instability. A
      significant number of chromosomal end-to-end fusions indicative of telomere
      dysfunction were noted in wt-Myc-expressing cells only. This study suggests that
      TAs may play a fundamental role in Myc-induced tumorigenesis and provides a novel
      way to dissect tumor initiation.

PMID- 16953227
TI  - Basement membrane component laminin-5 is a target of the tumor suppressor Smad4.
AB  - The tumor suppressor Smad4 is involved in carcinogenesis mainly of the pancreas
      and colon. Functional inactivation of Smad4 is a genetically late event that
      occurs upon transition from premalignant stages to invasive and metastatic
      growth. Smad4 encodes an intracellular messenger common to all signalling
      cascades induced by members of the transforming growth factor-beta (TGF-beta)
      superfamily of cytokines. Despite extensive knowledge about the mechanisms of TGF
      beta/Smad signal transduction, little is known about Smad4 targets involved in
      the transition to malignancy. The hallmark of invasive growth is a breakdown of
      the basement membrane (BM), a specialized sheet of extracellular matrix produced
      through cooperation of epithelial and stromal cells. Laminin-5, a heterotrimeric
      epithelial-derived BM component, is commonly lost in carcinomas but not in
      premalignant tumors. Herein, we report that in human colon and pancreatic tumor
      cells, Smad4 functions as a positive transcriptional regulator of all three genes
      encoding laminin-5. Coordinate re-expression of the three laminin-5 chains
      induced by reconstitution of Smad4 leads to secretion and deposition of the
      heterotrimeric molecule in BM-like structures. These data define the expression
      control of an essential BM component as a novel function for the tumor suppressor
      Smad4.

PMID- 16953228
TI  - Disruption of the retinoblastoma pathway by small interfering RNA and ectopic
      expression of the catalytic subunit of telomerase lead to immortalization of
      human ovarian surface epithelial cells.
AB  - The risk of developing ovarian cancer is about 1% over a lifetime, but it is the
      most deadly gynecologic cancer, in part due to lack of diagnostic markers for
      early-stage disease and cell model system for studying early neoplastic changes.
      Most existing immortal human ovarian surface epithelial cells were achieved by
      using viral protein such as SV40 T/t antigen or E6/E7, which inactivate multiple
      cellular pathways. In the current study, we used a small interfering RNA (siRNA)
      against the retinoblastoma gene (pRb) and ectopic expression of human telomerase
      reverse transcriptase (hTERT) to immortalize the primary ovarian epithelial cell
      line OSE137 and two additional human ovarian surface epithelial cells. The
      immortalized OSE137 showed increased telomerase activity, lengthened telomeres,
      increased G2/M phase, altered cell-cycle regulatory proteins but nontumorigenic.
      As both Rb and hTERT pathways are commonly altered in human ovarian cancer and
      these genetic changes are faithfully modeled in these cells without using viral
      protein, these immortal cells represent an authentic in vitro model system with
      which to study the initiation and progression of human ovarian cancer.

PMID- 16953229
TI  - Expression of the stem cell self-renewal gene Hiwi and risk of tumour-related
      death in patients with soft-tissue sarcoma.
AB  - Self-renewal is considered as a common property of stem cells. Dysregulation of
      stem cell self-renewal is likely a requirement for the development of cancer.
      Hiwi, the human Piwi gene, encodes a protein responsible for stem cell self
      renewal. In this study, we investigated the expression of Hiwi at the RNA level
      by real-time quantitative PCR in 65 primary soft-tissue sarcomas (STS) and
      ascertained its impact on prognosis for STS patients. In a multivariate Cox's
      proportional hazards regression model, we found that an increased expression of
      Hiwi mRNA is a significant negative prognostic factor for patients with STS
      (P=0.017; relative risk 4.6, 95% confidence interval (CI) 1.3-16.1) compared to
      medium expression of Hiwi transcript. However, a low expression of Hiwi
      transcript is correlated with a 2.4-fold (CI 0.7-8.0) increased risk, but this
      effect was not significant (P=0.17). Altogether, high-level expression of Hiwi
      mRNA identifies STS patients at high risk of tumour-related death. This is the
      first report showing a correlation between expression of a gene involved in stem
      cell self-renewal and prognosis of cancer patients.

PMID- 16953230
TI  - A positive feedback loop between hepatocyte growth factor receptor and beta
      catenin sustains colorectal cancer cell invasive growth.
AB  - Overexpressed or activated hepatocyte growth factor receptor, encoded by the MET
      proto-oncogene, was found in the majority of colorectal carcinomas (CRCs), whose
      stepwise progression to malignancy requires transcriptional activation of beta
      catenin. We here demonstrate that a functional crosstalk between Met and beta
      catenin signaling sustains and increases CRC cell invasive properties. Hepatocyte
      growth factor (HGF) stimulation prompts beta-catenin tyrosine phosphorylation and
      dissociation from Met, and upregulates beta-catenin expression via the
      phosphatidylinositol 3-kinase pathway in conditions that mimic those found by the
      invading and metastasizing cells. Additionally, a transcriptionally active form
      of beta-catenin, known to be oncogenic, enhances Met expression. Furthermore, HGF
      treatment increases the activity of the beta-catenin-regulated T-cell factor
      transcription factor in cells expressing the wild-type or the oncogenic beta
      catenin. In the mirror experiments, either Met or beta-catenin knocking down also
      reduces their protein level. In biological assays, beta-catenin knocking down
      abrogates the HGF-induced motile phenotype, whereas active beta-catenin fosters
      ligand-independent cell scattering. Met and beta-catenin also cooperate in
      promoting entry into the cell cycle and in protecting cells from apoptosis. In
      conclusion, Met and beta-catenin pathways are mutually activated in CRC cells.
      This might generate a self-amplifying positive feedback loop resulting in the
      upregulation of the invasive growth properties of CRC cells.

PMID- 16953231
TI  - Inhibition of the hyaluronan-CD44 interaction by merlin contributes to the tumor
      suppressor activity of merlin.
AB  - Mutation or loss of expression of merlin is responsible for neurofibromatosis
      type 2 (NF2), which is characterized by the development of schwannomas and other
      tumors of the nervous system. Like the ERM (ezrin-radixin-moesin) proteins,
      merlin interacts with CD44, a cell-surface receptor for hyaluronan (HA) that
      promotes tumorigenesis. However, the relationship between merlin and CD44 and the
      mechanism by which merlin exerts its tumor-suppressor function have not been
      elucidated. In the present study, we show that increased expression of wild-type
      merlin in Tr6BC1 schwannoma cells inhibits HA binding to CD44. Furthermore, we
      demonstrate that the residues required for this inhibitory effect and the
      interaction between CD44 and merlin lie within the first 50 amino acids of
      merlin. Overexpression of merlin inhibited subcutaneous growth of Tr6BC1 cells in
      immunocompromised Rag1 mice. In contrast, knocking down expression of endogenous
      merlin promoted tumor cell growth, as did overexpression of a merlin deletion
      mutant (merlinDel-1) that lacks the first 50 amino acids but not of other NH(2)
      terminal deletion mutants. Together, our results demonstrate that inhibition of
      the CD44-HA interaction contributes to the tumor-suppressor function of merlin,
      and they suggest that merlin inhibits tumor growth, at least in part, by
      negatively regulating CD44 function.

PMID- 16953232
TI  - Simultaneous downregulation of CDK inhibitors p18(Ink4c) and p27(Kip1) is
      required for MEN2A-RET-mediated mitogenesis.
AB  - Multiple endocrine neoplasia type 2A (MEN2A) is predisposed by mutations in the
      RET proto-oncogene. Low expression of the cyclin-dependent kinase inhibitor
      (CDKI) p27(Kip1) is present in thyroid tumors, and recent evidence demonstrates
      p27 downregulation by the active RET mutant, RET/PTC1, found in papillary thyroid
      carcinoma. This implicates decreased p27 activity as an important event during
      thyroid tumorigenesis. However, p27(-/-) mice develop MEN-like tumors only in
      combination with loss of another CDKI, p18(Ink4c). This suggests that p18 and p27
      functionally collaborate in suppression of tumorigenesis, that loss of both is
      critical in the development of MEN tumors and that both p18 and p27 are regulated
      by RET. We report that induction of the constitutively active MEN2A-specific RET
      mutant, RET2A(C634R), correlates with reduced p18/p27, and elevated cyclin D
      protein levels, leading to increased CDK activity, increased pRb phosphorylation
      and proliferation under growth arrest conditions. Mechanistically, RET2A
      represses p18/p27 mRNA levels while elevating cyclin D1 mRNA levels. RET2A
      expression also correlates with decreased p27 protein stability. RET2A-mediated
      regulation of p18 and p27, but not of cyclins D1 and D2, requires functional
      mitogen-activated protein kinase signaling. Additionally, RET2A-dependent p18
      repression is required and sufficient to increase cell proliferation. Perhaps
      most significantly, MEN2A adrenal tumors also display these changes in cell cycle
      expression profile, demonstrating the biological relevance of our cell culture
      studies. Our results demonstrate for the first time that RET2A regulates p18, and
      suggest that loss of not only p27 but also of p18 expression is a key step in MEN
      tumorigenesis.

PMID- 16953233
TI  - KRAS and BRAF oncogenic mutations in MSS colorectal carcinoma progression.
AB  - In sporadic colorectal cancer (CRC), KRAS are alternative to BRAF mutations and
      occur, respectively, in 30 and 10% of cases. Few reports addressed the
      association between KRAS-BRAF mutations and tumour progression specifically in
      sporadic microsatellite-stable (MSS) CRC. We screened KRAS and BRAF in 250 MSS
      primary CRC and 45 lymph node (LN) metastases and analysed the pathological
      features of the cases to understand the involvement of KRAS-BRAF activation in
      progression and metastasis. Forty-five per cent of primary MSS CRCs carried
      mutations in at least one of these genes and mutations were associated with wall
      invasion (P=0.02), presence and number of LN metastases (P=0.02 and P=0.03,
      respectively), distant metastases (P=0.004) and advanced stage (P=0.01). We
      demonstrated that KRAS and BRAF are alternative events in Tis and T1 MSS CRC and,
      KRAS rather than BRAF mutations, contributed to the progression of MSS CRC. The
      frequency of KRAS and/or BRAF mutations was higher in LN metastases than in
      primary carcinomas (P=0.0002). Mutated LN metastases displayed KRAS associated or
      not with BRAF mutations. BRAF mutations were never present as a single event.
      Concomitant KRAS and BRAF mutations increased along progression of MSS CRCs,
      suggesting that activation of both genes is likely to harbour a synergistic
      effect.

PMID- 16953234
TI  - NF-kappaB regulates the stability and activity of p73 by inducing its proteolytic
      degradation through a ubiquitin-dependent proteasome pathway.
AB  - Nuclear factor kappa B (NF-kappaB), which exists as heterodimeric complexes
      composed of p50 and p65, has been shown to play an important role in cell
      survival processes. In the present study, we found for the first time that NF
      kappaB has an ability to induce the ubiquitin-dependent proteasomal degradation
      of proapoptotic p73alpha. The activation of NF-kappaB in tumor necrosis factor
      alpha (TNF-alpha)-stimulated H1299 cells resulted in a significant reduction in
      the amounts of the endogenous p73alpha. Consistent with these results, TNF-alpha
      mediated downregulation of p73alpha was observed in wild-type (WT) mouse
      embryonic fibroblasts (MEFs) but not in p65-deficient MEFs. Ectopic expression of
      NF-kappaB decreased a half-life of p73alpha by increasing its ubiquitination
      levels, and thereby inhibiting the transcriptional activity as well as
      proapoptotic function of p73alpha, whereas NF-kappaB had undetectable effects on
      p53. Immunoprecipitation experiments demonstrated that, under our experimental
      conditions, NF-kappaB does not bind to p73alpha in mammalian cultured cells. In
      contrast to WT p65, the COOH-terminal deletion mutant of p65 (p65DeltaC) failed
      to reduce the expression levels of p73alpha, suggesting that NF-kappaB-mediated
      proteolytic degradation of p73alpha requires the transcriptional activity of NF
      kappaB. Taken together, our present results imply that NF-kappaB-mediated
      degradation of proapoptotic p73 is a novel inhibitory mechanism of p73 that
      regulates cell survival and death.

PMID- 16953235
TI  - Analysis of a missense variant of the human N-formyl peptide receptor that is
      associated with agonist-independent beta-arrestin association and indices of
      inflammation.
AB  - Formyl-Met-Leu-Phe (fMLP) is a potent chemoattractant molecule released from both
      bacteria and damaged mitochondria that activates fMLP receptors (FPR) leading to
      neutrophil chemotaxis, degranulation and superoxide production. A common missense
      single nucleotide polymorphism in the human FPR1 gene at nucleotide c.32C>T
      results in the amino-acid substitution, p.I11T, in the FPR1 extracellular amino
      terminus. The minor (c.32T) allele frequencies were 0.25, 0.27, 0.25, 0.15 and
      0.14 in healthy Caucasian, African, East Indian, Chinese and Native Canadian
      individuals, respectively. In subjects homozygous for the p.T11 allele, we find
      elevated serum concentrations of C-reactive protein, increased absolute counts of
      blood leukocytes and neutrophils, and erythrocyte sedimentation rates. When
      expressed in HEK 293 and RBL-2H3 cells a substantial proportion of FPR1 p.I11T
      variant is retained intracellularly and agonist-independent internalization of
      the FPR1 p.I11T variant, but not the wild-type FPR1, is constitutively associated
      with beta-arrestin2-GFP in vesicles. Moreover, basal N-acetyl-D-glucosaminidase
      release is increased in primary neutrophils isolated from subjects either
      heterozygous or homozygous for the FPR1 p.T11 allele. Taken together, the data
      suggest an increased receptor activity and phenotypic expression of increased
      inflammatory indices in subjects with the p.T11 allele.

PMID- 16953237
TI  - Predicted mechanisms of resistance to mTOR inhibitors.
AB  - The serine/threonine kinase, mTOR (mammalian Target of Rapamycin) has become a
      focus for cancer drug development. Rapamycins are highly specific inhibitors of
      mTOR and potently suppress tumour cell growth by retarding cells in G1 phase or
      potentially inducing apoptosis. Currently, both rapamycin and several analogues
      are being evaluated as anticancer agents in clinical trials. Results indicate
      that many human cancers have intrinsic resistance and tumours initially sensitive
      to rapamycins become refractory, demonstrating acquired resistance. Here, we
      consider mechanisms of resistance to inhibitors of mTOR.

PMID- 16953238
TI  - Heterogeneous nuclear ribonucleoprotein K is over expressed, aberrantly localised
      and is associated with poor prognosis in colorectal cancer.
AB  - Heterogeneous ribonucleoprotein K (hnRNP K) is a member of the hnRNP family which
      has several different cellular roles including transcription, mRNA shuttling, RNA
      editing and translation. Several reports implicate hnRNP K having a role in
      tumorigenesis, for instance hnRNP K increases transcription of the oncogene c-myc
      and hnRNP K expression is regulated by the p53/MDM 2 pathway. In this study
      comparing normal colon to colorectal cancer by proteomics, hnRNP K was identified
      as being overexpressed in this type of cancer. Immunohistochemistry with a
      monoclonal antibody to hnRNP K (which we developed) on colorectal cancer tissue
      microarray, confirmed that hnRNP K was overexpressed in colorectal cancer
      (P<0.001) and also showed that hnRNP K had an aberrant subcellular localisation
      in cancer cells. In normal colon hnRNP K was exclusively nuclear whereas in
      colorectal cancer the protein localised both in the cytoplasm and the nucleus.
      There were significant increases in both nuclear (P=0.007) and cytoplasmic
      (P=0.001) expression of hnRNP K in Dukes C tumours compared with early stage
      tumours. In Dukes C patient's good survival was associated with increased hnRNP K
      nuclear expression (P=0.0093). To elaborate on the recent observation that hnRNP
      K is regulated by p53, the expression profiles of these two proteins were also
      analysed. There was no correlation between hnRNP K and p53 expression, however,
      patients who presented tumours that were positive for hnRNP K and p53 had a
      poorer survival outcome (P=0.045).

PMID- 16953240
TI  - Efficient loading of dendritic cells following cryo and radiofrequency ablation
      in combination with immune modulation induces anti-tumour immunity.
AB  - Dendritic cells (DC) are professional antigen-presenting cells that play a
      pivotal role in the induction of immunity. Ex vivo-generated, tumour antigen
      loaded mature DC are currently exploited as cancer vaccines in clinical studies.
      However, antigen loading and maturation of DC directly in vivo would greatly
      facilitate the application of DC-based vaccines. We formerly showed in murine
      models that radiofrequency-mediated tumour destruction can provide an antigen
      source for the in vivo induction of anti-tumour immunity, and we explored the
      role of DC herein. In this paper we evaluate radiofrequency and cryo ablation for
      their ability to provide an antigen source for DC and compare this with an ex
      vivo-loaded DC vaccine. The data obtained with model antigens demonstrate that
      upon tumour destruction by radiofrequency ablation, up to 7% of the total
      draining lymph node (LN) DC contained antigen, whereas only few DC from the
      conventional vaccine reached the LN. Interestingly, following cryo ablation the
      amount of antigen-loaded DC is almost doubled. Analysis of surface markers
      revealed that both destruction methods were able to induce DC maturation.
      Finally, we show that in situ tumour ablation can be efficiently combined with
      immune modulation by anti-CTLA-4 antibodies or regulatory T-cell depletion. These
      combination treatments protected mice from the outgrowth of tumour challenges,
      and led to in vivo enhancement of tumour-specific T-cell numbers, which produced
      more IFN-gamma upon activation. Therefore, in situ tumour destruction in
      combination with immune modulation creates a unique, 'in situ DC-vaccine' that is
      readily applicable in the clinic without prior knowledge of tumour antigens.

PMID- 16953239
TI  - Phase II trial of radiotherapy after hyperbaric oxygenation with chemotherapy for
      high-grade gliomas.
AB  - We conducted a phase II trial to evaluate the efficacy and toxicity of
      radiotherapy immediately after hyperbaric oxygenation (HBO) with chemotherapy in
      adults with high-grade gliomas. Patients with histologically confirmed high-grade
      gliomas were administered radiotherapy in daily 2 Gy fractions for 5 consecutive
      days per week up to a total dose of 60 Gy. Each fraction was administered
      immediately after HBO with the period of time from completion of decompression to
      irradiation being less than 15 min. Chemotherapy consisted of procarbazine,
      nimustine (ACNU) and vincristine and was administered during and after
      radiotherapy. A total of 41 patients (31 patients with glioblastoma and 10
      patients with grade 3 gliomas) were enrolled. All 41 patients were able to
      complete a total radiotherapy dose of 60 Gy immediately after HBO with one course
      of concurrent chemotherapy. Of 30 assessable patients, 17 (57%) had an objective
      response including four CR and 13 PR. The median time to progression and the
      median survival time in glioblastoma patients were 12.3 months and 17.3 months,
      respectively. On univariate analysis, histologic grade (P=0.0001) and Karnofsky
      performance status (P=0.036) had a significant impact on survival, and on
      multivariate analysis, histologic grade alone was a significant prognostic factor
      for survival (P=0.001). Although grade 4 leukopenia and grade 4 thrombocytopenia
      occurred in 10 and 7% of all patients, respectively, these were transient with no
      patients developing neutropenic fever or intracranial haemorrhage. No serious
      nonhaematological or late toxicities were seen. These results indicated that
      radiotherapy delivered immediately after HBO with chemotherapy was safe with
      virtually no late toxicity in patients with high-grade gliomas. Further studies
      are required to strictly evaluate the effectiveness of radiotherapy after HBO for
      these tumours.

PMID- 16953241
TI  - Somatostatin receptor expression, tumour response, and quality of life in
      patients with advanced hepatocellular carcinoma treated with long-acting
      octreotide.
AB  - Octreotide may extend survival in hepatocellular carcinoma (HCC). Forty-one per
      cent of HCCs have high-affinity somatostatin receptors. We aimed to determine the
      feasibility, safety, and activity of long-acting octreotide in advanced HCC; to
      identify the best method for assessing somatostatin receptor expression; to
      relate receptor expression to clinical outcomes; and to evaluate toxicity. Sixty
      three patients with advanced HCC received intramuscular long-acting octreotide 20
      mg monthly until progression or toxicity. Median age was 67 years (range 28-81
      years), male 81%, Child-Pugh A 83%, and B 17%. The aetiologies of chronic liver
      disease were alcohol (22%), viral hepatitis (44%), and haemochromatosis (6%).
      Prior treatments for HCC included surgery (8%), chemotherapy (2%), local ablation
      (11%), and chemoembolisation (6%). One patient had an objective partial tumour
      response (2%, 95% CI 0-9%). Serum alpha-fetoprotein levels decreased more than
      50% in four (6%). Median survival was 8 months. Thirty four of 61 patients (56%)
      had receptor expression detected by scintigraphy; no clear relationship with
      clinical outcomes was identified. There were few grade 3 or 4 toxicities:
      hyperglycaemia (8%), hypoglycaemia (2%), diarrhoea (5%), and anorexia (2%).
      Patients reported improvements in some symptoms, but no major changes in quality
      of life were detected. Long-acting octreotide is safe in advanced HCC. We found
      little evidence of anticancer activity. A definitive randomised trial would
      identify whether patients benefit from this treatment in other ways.

PMID- 16953243
TI  - Ejaculatory dysfunction: progress in rarely acknowledged sexual problems.

PMID- 16953242
TI  - ReSETting PP2A tumour suppressor activity in blast crisis and imatinib-resistant
      chronic myelogenous leukaemia.
AB  - The deregulated kinase activity of p210-BCR/ABL oncoproteins, hallmark of chronic
      myelogenous leukaemia (CML), induces and sustains the leukaemic phenotype, and
      contributes to disease progression. Imatinib mesylate, a BCR/ABL kinase
      inhibitor, is effective in most of chronic phase CML patients. However, a
      significant percentage of CML patients develop resistance to imatinib and/or
      still progresses to blast crisis, a disease stage that is often refractory to
      imatinib therapy. Furthermore, there is compelling evidence indicating that the
      CML leukaemia stem cell is also resistant to imatinib. Thus, there is still a
      need for new drugs that, if combined with imatinib, will decrease the rate of
      relapse, fully overcome imatinib resistance and prevent blastic transformation of
      CML. We recently reported that the activity of the tumour suppressor protein
      phosphatase 2A (PP2A) is markedly inhibited in blast crisis CML patient cells and
      that molecular or pharmacologic re-activation of PP2A phosphatase led to growth
      suppression, enhanced apoptosis, impaired clonogenic potential and decreased in
      vivo leukaemogenesis of imatinib-sensitive and -resistant (T315I included) CML-BC
      patient cells and/or BCR/ABL+ myeloid progenitor cell lines. Thus, the
      combination of PP2A phosphatase-activating and BCR/ABL kinase-inhibiting drugs
      may represent a powerful therapeutic strategy for blast crisis CML patients.

PMID- 16953244
TI  - Rapid ejaculation: a review of nosology, prevalence and treatment.
AB  - Information concerning the epidemiology, etiology and treatment of premature
      (rapid) ejaculation is reviewed. Evidence concerning the prevalence of premature
      ejaculation indicates that subjective concern about rapid ejaculation is a common
      concern worldwide. Hypotheses concerning the pathogenesis of premature
      ejaculation include: (1) that it is a learned pattern of ejaculation maintained
      by interpersonal anxiety, (2) that it is the result of dysfunction in central or
      peripheral mechanisms regulating ejaculatory thresholds and (3) that it is a
      normal variant in ejaculatory latency. Current evidence based treatment
      interventions include behavioral psychotherapy and the use of pharmacological
      agents, including topical anesthetic agents and selective serotonin reuptake
      inhibitors.

PMID- 16953245
TI  - Ejaculatory dysfunction: progress in a rarely recognized sexual problem.

PMID- 16953246
TI  - Ejaculatory dysfunction and depression: pharmacological and psychobiological
      interactions.
AB  - In recent years, increased attention has been focused on antidepressant
      associated sexual dysfunction, largely because of the widespread use of serotonin
      specific reuptake inhibitors (SSRIs) and the recognition that such side effects
      can have a negative impact on treatment compliance. Data suggest that
      serotonergic antidepressants are associated with delayed ejaculation and
      anorgasmia, although these sexual problems are also linked to depression and to
      age. In this review, we discuss central mediators of normal orgasmic functioning
      and dysfunction, the relationship between depression and sexual dysfunction,
      possible mechanisms for SSRI-associated sexual dysfunction, and evolving
      treatment strategies.

PMID- 16953247
TI  - Premature ejaculation: definition and prevalence.
AB  - Premature ejaculation (PE) is likely the most common sexual dysfunction in men,
      with a worldwide prevalence of approximately 30%. To date, the lack of a
      universally acknowledged definition of PE has complicated the examination and
      analysis of PE in clinical and research-related settings. The impact of PE on men
      and their partners also needs to be clearly defined. Clearly, a better
      understanding of the epidemiology of this disorder, especially with regard to
      prevalence and risk factors, is necessary. The prevalence of PE appears to vary
      across socio-cultural and geographic populations. The elucidation of the etiology
      of PE and risk factors associated with PE has been difficult. However, several
      risk factors for PE exist that have strong support in the literature. Clearly, an
      improved and universal definition and understanding of PE and its epidemiology
      will improve the clinical management of PE and the success of future
      epidemiologic studies and clinical trials.

PMID- 16953248
TI  - From The Origin of Species to the origin of bacterial flagella.
AB  - In the recent Dover trial, and elsewhere, the 'Intelligent Design' movement has
      championed the bacterial flagellum as an irreducibly complex system that, it is
      claimed, could not have evolved through natural selection. Here we explore the
      arguments in favour of viewing bacterial flagella as evolved, rather than
      designed, entities. We dismiss the need for any great conceptual leaps in
      creating a model of flagellar evolution and speculate as to how an experimental
      programme focused on this topic might look.

PMID- 16953249
TI  - Gene therapy progress and prospects: non-viral gene therapy by systemic delivery.
AB  - Non-viral vectors continue to be an attractive alternative to viral vectors due
      to their safety, versatility and ease of preparation and scale-up. Over the past
      few years, investigators have been successful in developing gene carriers that
      can be targeted to the disease site. Several different delivery vectors for
      systemic use have been developed by different groups for plasmid DNA and
      oligonucleotide. Most of them are designed for targeted tumor therapy. The
      mechanism of inflammatory toxicity, the major toxicity of cationic lipoplex, has
      been studied and managed. In this review, we focus on the progress made over the
      last 2 years. We also discuss some future prospects for gene delivery.

PMID- 16953251
TI  - Personality characteristics in obesity and relationship with successful weight
      loss.
AB  - OBJECTIVE: Personality influences lifestyle behaviors. Therefore, certain
      personality traits could contribute to obesity and the response to behaviorally
      based weight loss therapy. PURPOSE: The aims of this study were to test the
      hypothesis that personality characteristics differ between lean and obese persons
      in the community, obese persons in the community and obese persons seeking weight
      loss therapy by enrolling in a comprehensive weight loss program, and in obese
      persons who were successful and unsuccessful in achieving behavioral therapy
      induced weight loss. METHODS: The Temperament and Character Inventory was
      administered to 264 lean (body mass index (BMI) <25 kg/m(2)) and 56 obese (BMI>
      or =35 kg/m(2)) subjects from the St Louis community and 183 obese patients
      (BMI=44+/-10 kg/m(2)) enrolled in the Washington University Weight Management
      Program (WUWMP), which involved weekly group behavioral therapy and diet
      education sessions for 22 weeks. RESULTS: Compared with lean subjects, obese
      subjects in the community scored higher in novelty seeking (19.7+/-5.9 vs 16.2+/
      6.0, P<0.05), lower in Persistence (4.1+/-1.8 vs 4.8+/-1.7, P<0.05) and lower in
      self-directedness (32.1+/-7.6 vs 34.3+/-6.6, P<0.05.) Patients enrolled in the
      WUWMP scored higher than obese persons in the general population in both Reward
      Dependence (17.1+/-4.2 vs 15.7+/-4.3, P<0.05) and cooperativeness (36.9+/-5.4 vs
      34.5+/-6.2, P<0.05). Patients who were successful in losing weight (>10% weight
      loss) after 22 weeks of behavioral therapy scored lower in novelty seeking than
      those who were unsuccessful in losing weight (<5% weight loss) (17.6+/-5.9 vs
      20.2+/-5.9, P<0.05). DISCUSSION: These results suggest that personality traits
      differ between lean and obese persons, and between obese persons who enroll and
      who do not enroll in a comprehensive weight management program. Moreover, high
      scores in novelty seeking are associated with decreased success in achieving
      behavioral therapy-induced weight loss.

PMID- 16953252
TI  - Leptin secretion is related to glucose-derived lipogenesis in isolated
      adipocytes.
AB  - OBJECTIVE: Leptin secretion in rats is regulated acutely by nutritional state.
      Insulin plays an important role in this acute nutritional regulation both
      directly and indirectly through effects on glucose metabolism. The aim of this
      study was to investigate if the fasting-induced suppression of leptin secretion
      was reversed by incubation under conditions mimicking nutritional repletion.
      DESIGN: Leptin secretion and glucose metabolism were measured following
      incubation with glucose and insulin in adipocytes isolated from fed and fasted
      rats. RESULTS: Leptin secretion was stimulated by incubation with glucose and
      insulin in adipocytes isolated from fed but not from fasted rats as was glucose
      flux through oxidative and lipogenic pathways. Ob expression and intracellular
      leptin content were decreased in adipocytes isolated from fasted rats throughout
      the whole incubation period. Suppression of glucose metabolism with cytochalasin
      B was accompanied by suppression of leptin secretion. The amount of leptin
      secretion correlated with the glucose incorporated into lipid under insulin
      stimulated conditions. CONCLUSIONS: It is proposed that glucose incorporation
      into lipid, at least during insulin-stimulated conditions, reflects the metabolic
      status of the adipocyte and may be a more important regulator of leptin
      production and secretion than circulating glucose or insulin levels.

PMID- 16953253
TI  - Testing a model of physical activity and obesity tracking from youth to
      adulthood: the cardiovascular risk in young Finns study.
AB  - OBJECTIVE: To test a potential model of the relationship between physical
      activity and obesity from youth to adulthood. DESIGN: Longitudinal study data
      from the cardiovascular risk in young Finns study. SUBJECTS: A total of 1319 boys
      (n=626) and girls (n=693) aged 9, 12, 15 and 18 years were randomly selected from
      five university towns and their rural surroundings in 1980. They were followed up
      for 21 years. In 2001 they were 30, 33, 36 and 39 years old. MEASUREMENTS:
      Physical activity was assessed by a short questionnaire at two measurement
      points. Obesity was measured by body mass index (BMI) and sum of skinfolds in
      1980 and BMI and waist circumference in 2001. RESULTS: Structural equation
      analysis (LISREL) indicated that the prevalence of abdominal obesity in adulthood
      was directly affected by adult physical activity (beta (beta)=-0.16, t=-4.02, P<
      0.05 for men, beta=-0.12, t=-3.35, P<0.05 for women) and indirectly via youth
      physical activity (beta=-0.10, t=-4.68, P< 0.05 for men, beta=-0.07, t=-4.54,
      P<0.05 for women). Obesity tracked significantly from youth to adulthood
      (beta=0.41, t=11.13, P<0.05 for men, beta=0.34, t=9.39, P<0.05 for women). Youth
      physical activity might reduce body weight in youth but was not directly
      associated with adult abdominal obesity in either men or women. The model
      accounted 19% of abdominal obesity in men and 13% in women. The path from youth
      physical activity to adult obesity through youth obesity seemed to be stronger
      than the path through adult physical activity. CONCLUSIONS: This study lends
      general support to the hypothesized model that abdominal obesity in adulthood is
      directly related to adult physical activity and youth overall obesity in both
      sexes. Youth physical activity had an indirect effect on abdominal obesity
      through the maintenance of physical activity in adulthood. Participation in and
      maintaining physical activity from youth to adulthood may have an important role
      in reducing obesity in adulthood.

PMID- 16953254
TI  - Is the association between physical activity and body mass index obesity
      dependent?
AB  - BACKGROUND: Most studies indicate an inverse relationship between physical
      activity (PA) and body mass index (BMI). However, the impact of obesity on this
      relationship is unclear. OBJECTIVE: To scrutinize the BMI/PA relationship by
      analysing multiple categories of PA from a sample with a wide BMI range. DESIGN:
      PA was measured with accelerometry for 7 consecutive days during free-living
      conditions in 85 severely obese outpatients (mean BMI 42.7 kg/m(2) (s.d. 6.1);
      age 43.0 year (12.6)) and 193 control subjects (24.0 kg/m(2) (3.5); 41.6 year
      (13.0)). Six categories of PA were calculated from the accelerometer data
      (min/day of sedentary time, min/day of light PA, min/day of moderate PA, min/day
      of vigorous PA, activity counts/day and steps/day). Participants were stratified
      in obese and non-obese subgroups (BMI=30 kg/m(2) as cutoff). Associations between
      BMI and PA were examined in the total sample, and in subgroups. The impact of sex
      and age on the BMI/PA association was tested. RESULTS: In the total sample, the
      association between BMI and PA was significant in all PA categories except for
      time spent sedentary (P=0.68). However, in subgroup analyses, the association
      between BMI and PA in non-obese was only significant for activity counts/day (r=
      0.16, P<0.05) and vigorous intensity PA (r=-0.15, P=0.05). After adjustment for
      age, vigorous PA remained significantly associated with BMI in the non-obese (r=
      0.17, P<0.05). In obese individuals, significant associations between BMI and PA
      were found for all six PA categories (age adjusted), sedentary time (r=0.26,
      P=0.05), light PA (r=-0.30, P<0.01), moderate PA (r=-0.35, P<0.01), vigorous PA
      (r=-0.39, P<0.001), activity counts/day (r=-0.50, P<0.001) and steps/day (r=
      0.54, P<0.001). CONCLUSION: The association between PA and BMI was weak in non
      obese individuals. In contrast, BMI was highly significantly associated with PA
      in obese individuals. Longitudinal studies are needed to tease out the direction
      of association between PA and BMI across BMI categories, as the cross-sectional
      associations seem to be dependent on obesity status.

PMID- 16953255
TI  - Eating patterns and dietary composition in relation to BMI in younger and older
      adults.
AB  - OBJECTIVE: To compare relative associations of eating patterns and dietary
      composition with body mass index (BMI) in younger (aged 20-59 years, n=1792) and
      older (aged 60-90 years, n=893) participants in the Continuing Survey of Food
      Intakes by Individuals, collected 1994-1996. METHODS: Data from two 24-h dietary
      recalls from individuals reporting physiologically plausible energy intake
      (within +/-22% of predicted energy requirements, based on previously published
      methods) were used. RESULTS: Mean reported energy intake was 96 and 95% of
      predicted energy requirements in younger and older subjects, respectively. Older
      subjects were less likely than younger subjects to skip a meal, but snacking was
      common in both age groups. Fiber density was significantly higher in the older
      group. A higher BMI in both age groups was associated with a higher total daily
      energy intake, and higher energy intakes at all eating occasions. In both age
      groups, eating frequency was positively associated with energy intake, and eating
      more than three times a day was associated with being overweight or obese. In the
      younger group but not the older group, a lower fiber density coupled with higher
      percentage of energy from fat was independently associated with having a higher
      BMI. CONCLUSIONS: While no one eating occasion contributes more than any other to
      excess adiposity, eating more often than three times a day may play a role in
      overweight and obesity in both younger and older persons. A reduced satiety
      response to dietary fiber in addition to lower energy expenditure may potentially
      further contribute to weight gain in older persons.

PMID- 16953256
TI  - Comparison of anthropometric, area- and volume-based assessment of abdominal
      subcutaneous and visceral adipose tissue volumes using multi-detector computed
      tomography.
AB  - PURPOSE: Cross-sectional imaging may enable accurate localization and
      quantification of subcutaneous and visceral adipose tissue. The reproducibility
      of multi-detector computed tomography (MDCT)-based volumetric quantification of
      abdominal adipose tissue and the ability to depict age- and gender-related
      characteristics of adipose tissue deposition have not been reported. METHODS: We
      evaluated a random subset of 100 Caucasian subjects (age range: 37-83 years; 49%
      women) of the Framingham Heart Study offspring cohort who underwent MDCT
      scanning. Two readers measured subcutaneous and visceral adipose tissue volumes
      (SAV and VAV; cm(3)) and areas (SAA and VAA; cm(2)) as well as abdominal sagital
      diameter (SD) and waist circumference (WC). RESULTS: Inter-reader reproducibility
      was excellent (relative difference: -0.34+/-0.52% for SAV and 0.59+/-0.93% for
      VAV, intra-class correlation (ICC)=0.99 each). The mean SAA/VAA ratio was
      significantly different from the mean SAV/VAV ratio (2.0+/-1.2 vs 1.7+/-0.9;
      P<0.001). The ratio of SAV/VAV was only weakly inversely associated with SD (ICC=
      0.32, P=0.01) and not significantly associated with WC (ICC=-0.14, P=0.14) or
      body mass index (ICC=-0.17, P=0.09). The mean SAV/VAV ratio was significantly
      different between participants <60 vs >60 years (1.9+/-1.0 vs 1.5+/-0.7; P<0.001)
      and between men and women (1.2+/-0.5 vs 2.2+/-0.9; P<0.001). CONCLUSION: This
      study demonstrates that MDCT-based volumetric quantification of abdominal adipose
      tissue is highly reproducible. In addition, our results suggest that volumetric
      measurements can depict age- and gender-related differences of visceral and
      subcutaneous abdominal adipose tissue deposition. Further research is warranted
      to assess whether volumetric measurements may substantially improve the
      predictive value of obesity measures for insulin resistance, type 2 diabetes
      mellitus and other diseases.

PMID- 16953257
TI  - Prevalence of the metabolic syndrome in Zhejiang Chinese obese children and
      adolescents and the effect of metformin combined with lifestyle intervention.
AB  - OBJECTIVE: We aimed to evaluate the prevalence of metabolic syndrome (MS) in a
      group of obese children and adolescents in Zhejiang in the south of China, and to
      compare risk factors such as insulin resistance, adiponectin level and impaired
      glucose tolerance (IGT) etc with that of simple obese group (SOB) and non-obese
      healthy group, and also to evaluate the effect of metformin and lifestyle
      intervention in MS group by up to a 3-month follow-up. METHODS: Three hundred and
      forty eight moderately or severely obese adolescents aged between 7 and 16 years
      were enrolled. Oral glucose tolerance test (OGTT), biochemical indicators, blood
      pressure and body mass index (BMI) were assessed in all of them. Three subgroups
      were selected (MS group, SOB and healthy control). Adiponectin levels, Whole body
      insulin sensitive index (WBISI), homeostasis model of insulin resistance (HOMA
      IR), plasma lipid and blood pressure were compared in these three groups. Thirty
      out of thirty-six MS subjects with age over 10 years received metformin treatment
      combined with lifestyle modification. RESULTS: (1) The prevalence of MS was
      10.34% among all obese subjects, which increased with the severity of obesity and
      reached 22.1% in severely obese children and adolescents. The occurrence of more
      than one complication reached 72.13%. The incidence of type 2 diabetes and IGT
      were 1.44 and 1.44% respectively. (2) BMI, waist-to-hip ratio (WHR) and HOMA-IR
      increased stepwise in the control group, SOB and MS group, whereas serum
      adiponectin and WBISI decreased stepwise (all P<0.01). Systolic pressure,
      triglyceride, total cholesterol, low-density lipoprotein cholesterol and
      postprandial 2-h blood glucose in the MS group increased significantly compared
      to those in control and SOBs (all P<0.01). A correlation analysis showed that
      serum levels of adiponectin and WBISI were associated with the components of MS
      (all P<0.05). (3) After metformin and lifestyle intervention, clinical symptoms
      were ameliorated, serum adiponectin levels were actually increased and HOMA-IR
      was dropped in 20/30 MS children who had finished a 3-months follow-up (all
      P<0.01). CONCLUSION: The prevalence of MS in severely obese children and
      adolescents in Zhejiang area has reached a high level. Insulin resistance and
      hypoadiponectinemia were found in these MS children. Metformin combined with
      lifestyle modification was confirmed to be efficient and safe in treating the
      obese adolescents with MS.

PMID- 16953258
TI  - Waist circumference and body mass index in Chinese children: cutoff values for
      predicting cardiovascular risk factors.
AB  - BACKGROUND: Body mass index (BMI) and waist circumference (WC) correlate with
      cardiovascular (CV) risk factors in childhood which track into adulthood. WC
      provides a measure of central obesity, which has been specifically associated
      with CV risk factors. Reference standards for WC, and for WC and BMI risk
      threshold values are not established in Chinese children. OBJECTIVES: To
      construct reference percentile charts of WC, establish relationships between WC,
      BMI and other risk factors, and propose WC and BMI threshold values predictive of
      CV risk factors in Hong Kong ethnic Chinese children. METHODS: Weight, height,
      waist and hip circumference were measured in 2593 (52% boys, 47% girls) randomly
      sampled Hong Kong school children aged 6-12 years. In 958 of these and 97
      additional overweight children (n=1055), the relationships between WC, BMI,
      waist/hip and waist/height ratio and six age-adjusted CV risk factors (>85%
      percentile levels of blood pressure (BP), fasting triglycerides, low-density
      lipoprotein (LDL) cholesterol, glucose and insulin levels, and <15% percentile
      levels of high-density lipoprotein (HDL) cholesterol) were studied. Receiver
      operating characteristic analysis was employed to derive optimal age-adjusted sex
      specific WC and BMI thresholds for predicting these measures of risk. RESULTS: WC
      percentiles were constructed. WC correlated slightly more than BMI with CV risk
      factors and most strongly with insulin and systolic BP, but poorly or not with
      LDL and glucose. Optimal WC and BMI risk thresholds for predicting four of these
      six CV risk factors were ca. the 85th percentiles (sensitivities approximately
      0.8, specificities approximately 0.87) with age-specific cutoff values in
      girls/boys from approximately 57/58 to approximately 71/76 cm and 17/18 to 22/23
      kg/m(2). CONCLUSION: These are the first set of WC reference data for Chinese
      children. WC risk cutoff values are proposed which, despite a smaller waist in
      Chinese children, are similar to those reported for American children. WC
      percentiles may reflect population risk.

PMID- 16953259
TI  - Features of the metabolic syndrome are modulated by an interaction between the
      peroxisome proliferator-activated receptor-delta -87T>C polymorphism and dietary
      fat in French-Canadians.
AB  - OBJECTIVE: We verified whether genetic variants in this gene are associated with
      the MS and whether dietary fatty acids interact with the -87T>C polymorphism.
      METHODS: By direct sequencing, we identified 15 variants in the PPAR-delta gene
      and analyses were pursued with the -87T>C polymorphism for 340 subjects. RESULTS:
      Metabolic variables were comparable among each genotype group. The -87T>C
      polymorphism, fat intake and the interaction accounted, respectively for 2.2, 1.9
      and 1.5% of the variance in high-density lipoprotein cholesterol (HDL-C) levels
      (P<0.05) (age, sex and energy intake were included into the model). The total
      cholesterol/HDL-C ratio was also modulated by a gene-diet interaction and by the 
      87T>C polymorphism (P<0.05). No gene-diet interaction effects were observed for
      other features of the MS. The age- and sex-adjusted odds ratio (OR) of exhibiting
      three or more features of the MS when carrying the -87C allele was 0.62 (P=0.04)
      compared to -87T/T. However, in subjects consuming less than 34.4% of energy from
      fat (median of fat consumption), the OR in carriers of the -87C allele was of
      0.42 (P=0.008). CONCLUSION: These data suggest that the PPAR-delta -87T>C
      polymorphism may be associated with a lower risk to exhibit the MS and this
      association is influenced by dietary fat intake. The metabolic syndrome (MS) is
      influenced by genetic and environmental factors. Peroxisome proliferator
      activated receptor delta (PPAR-delta), a transcription factor involved in lipid
      metabolism, is a candidate gene for the MS.

PMID- 16953260
TI  - Characterization of obese individuals who claim to detect no relationship between
      their eating pattern and sensations of hunger or fullness.
AB  - OBJECTIVE: To study the phenomenon that obese subjects show considerable
      individual variability in their reported relationships between eating and
      sensations of hunger and fullness. DESIGN: A laboratory study of the relationship
      between eating behaviour traits and the episodic oscillations in sensations of
      hunger and fullness in response to obligatory, fixed energy breakfast (481 kcal)
      and lunch (675 kcal) meals. SUBJECTS: Obese subjects were divided into two groups
      based on their responses to four 'screening' questions associated with their
      habitual experience of hunger and fullness sensations before and after eating:
      those who experienced sensations of hunger and fullness related to eating
      (Related-R; n=20, body mass index (BMI)=42.4 kg/m(2)) and those for whom eating
      was not related to hunger or fullness sensations (Unrelated - UR; n=19, BMI=41.3
      kg/m(2)). In addition, a control, lean group (Control - C; n=14, BMI=22.6
      kg/m(2)) who experienced sensations of hunger and fullness related to eating was
      studied. MEASUREMENTS: The Three-Factor Eating Questionnaire (TFEQ) was used to
      measure the eating behaviour traits, disinhibition, restraint and hunger.
      Profiles of subjective appetite sensations were continuously monitored across the
      day using visual analogue scales. RESULTS: All groups displayed clear meal
      related oscillations in subjective sensations of hunger, fullness, desire to eat
      and prospective consumption. In contrast, the TFEQ disinhibition and hunger
      scores (but not restraint scores) were significantly different (P<0.05) between
      the groups ((UR; D=13.5+/-0.5, H=10.0+/-0.5), R (D 7.5+/-0.6, H 6.1+/-0.4), C(D
      3.7+/-0.5, H 3.7+/-0.5)). In addition, analysis of the intra-meal changes in
      subjective appetite sensations revealed that the UR group displayed a smaller
      meal-induced suppression of hunger and elevation of fullness. CONCLUSION: These
      data indicate that the reported relationship between eating and hunger/fullness
      was associated with obese individuals showing high or low disinhibition scores.
      In addition, the data suggest that the processes underlying disinhibition may be
      associated with a modulation of the recognition of meal-related satiety
      sensations.

PMID- 16953261
TI  - Cetilistat (ATL-962), a novel lipase inhibitor: a 12-week randomized, placebo
      controlled study of weight reduction in obese patients.
AB  - OBJECTIVE: To determine the efficacy, safety and tolerability of cetilistat (ATL
      962), a novel inhibitor of gastrointestinal (GI) lipases, in obese patients.
      DESIGN: Phase II, multicentre, randomized, placebo-controlled, parallel group
      study. Enrolled patients (N=442) were advised a hypocaloric diet (deficient by
      500 kcal per day, 30% of calories from fat) for a 2-week run-in period. Patients
      who satisfied the entry criteria (N=371) continued on the hypocaloric diet and
      were randomized to either placebo or one of three different doses of cetilistat
      (60 mg three times daily t.i.d., 120 mg t.i.d. and 240 mg t.i.d.) for 12 weeks,
      followed by a 4-week post-treatment follow-up. Safety, tolerability and body
      weight were assessed, together with other parameters associated with obesity.
      OUTCOME MEASURES: The primary outcome measure was absolute change in body weight
      from baseline. Secondary outcomes included the proportion of patients achieving
      pre-defined weight loss targets, changes from baseline in waist circumference and
      in blood lipids. GI tolerability criteria were specifically assessed, as was
      safety. RESULTS: Treatment with cetilistat reduced mean body weight to similar
      extents at all doses, which were statistically significant compared with placebo
      (60 mg t.i.d. 3.3 kg, P<0.03; 120 mg t.i.d. 3.5 kg, P=0.02; 240 mg t.i.d. 4.1 kg,
      P<0.001). Total serum and low-density lipoprotein cholesterol levels were
      likewise significantly reduced by 3-11% at all doses of cetilistat. Cetilistat
      was well tolerated. The frequency of withdrawal owing to treatment-emergent
      adverse events was similar between cetilistat-treated groups (5.3-7.6%) and
      placebo (7.6%). Adverse events were generally mild to moderate in intensity,
      occurred on only one occasion and were mostly GI in nature. The incidence of GI
      adverse events was increased in the cetilistat-treated groups compared to
      placebo. However, those GI adverse events, such as flatus with discharge and oily
      spotting, only occurred in 1.8-2.8% of subjects in the cetilistat-treated groups.
      CONCLUSIONS: Cetilistat produced a clinically and statistically significant
      weight loss in obese patients in this short-term 12-week study. This was
      accompanied by significant improvements in other obesity-related parameters.
      Cetilistat treatment was well tolerated. The risk-benefit demonstrated in this
      study in terms of weight loss vs intolerable GI adverse effects shows that
      cetilistat merits further evaluation for the pharmacotherapy of obesity and
      related disorders.

PMID- 16953262
TI  - Emerging themes in the treatment of venous thromboembolism.

PMID- 16953263
TI  - Initial treatment of venous thromboembolism.
AB  - Immediate anticoagulant treatment is essential to reduce morbidity and mortality
      in patients with acute venous thromboembolism (VTE). Currently, rapid
      anticoagulation can only be achieved with parenteral anticoagulants, such as
      heparin or low-molecular-weight heparin (LMWH). Weight-adjusted LMWH is the
      treatment of choice, because it produces predictable anticoagulation and does not
      require coagulation monitoring. If heparin is used, the activated partial
      thromboplastin time must be monitored and the heparin dose adjusted to ensure a
      therapeutic level of anticoagulation. Heparin is recommended for patients with
      renal impairment and for those at high risk of bleeding. The selective factor Xa
      inhibitor fondaparinux is a recently introduced alternative to heparin or LMWH
      for initial VTE treatment. Heparin, LMWH, or fondaparinux should be given for at
      least five to seven days. Vitamin K antagonists should be initiated on the first
      day, or as soon as possible, in patients who are candidates for an oral
      anticoagulant. An oral anticoagulant agent to be used without laboratory
      monitoring for both acute and long-term treatment of VTE remains an unsolved
      clinical need in the treatment of VTE.

PMID- 16953264
TI  - Role of fibrinolysis and interventional therapy for acute venous thromboembolism.
AB  - The initial goals of treatment for venous thromboembolism (VTE) are usually
      achieved with anticoagulation. This review focuses on fibrinolysis and
      interventional therapy in VTE, treatments whose indications are much more
      controversial. The benefit-to-risk ratio of fibrinolysis in deep vein thrombosis
      (DVT) is dubious. Thrombolytic treatment is recommended for unstable patients
      with pulmonary embolism (PE), although these patients represent less than 5% of
      all patients hospitalized for PE. The use of thrombolytic treatment in patients
      with sub-massive PE remains controversial. Two indications are widely recognized
      for inferior vena cava filters: the first is a permanent or temporary
      contraindication to anticoagulation, in patients with proximal DVT or PE. The
      second is the occurrence of PE or propagation of the thrombus in patients treated
      for DVT or recurrence in patients with PE. The PREPIC study demonstrated that in
      acute VTE, vena cava filters reduced the risk of PE but increased that of DVT and
      had no effect on survival. The fact that prevention of PE is mainly observed
      during the short initial period following the diagnosis of an acute VTE event
      justifies a new randomized study with the use of retrievable filters as an
      adjuvant to anticoagulation in high risk patients with PE.

PMID- 16953265
TI  - New concepts in optimal management of anticoagulant therapy for extended
      treatment of venous thromboembolism.
AB  - Recent trials on secondary prophylaxis after venous thromboembolism (VTE) have
      provided a wealth of data on the risk factors for recurrence and, to some extent,
      also for bleeding. Some of the results are consistent across the studies, but
      there are also conflicting data. Certain risk factors, such as pulmonary embolism
      versus deep vein thrombosis or presence of cardiolipin antibodies, have a more
      pronounced influence on the risk early in the course of disease. Others, such as
      hereditary thrombophilic defects, seem to gain importance over many years of
      follow-up. Therefore, it can be difficult to make decisions on an individual
      patient basis. In this article, data from important and illustrative trials have
      been extracted and compared and controversies highlighted. The conclusions drawn
      should help clinicians make balanced decisions on the optimal duration of
      anticoagulation after an episode of VTE.

PMID- 16953266
TI  - Racial and gender differences in the incidence of recurrent venous
      thromboembolism.
AB  - Men have been reported to have a higher incidence of recurrent venous
      thromboembolism than women. However, it is not known if this gender effect holds
      among different racial/ethnic groups and for both venous thrombosis and pulmonary
      embolism. We conducted a retrospective analysis of 18- to 65-year-old Caucasian,
      African-American and Hispanic cases hospitalized in California with unprovoked
      venous thromboembolism. The principal outcome was recurrent venous
      thromboembolism 7-60 months after the index event. Among 11,514 cases that were
      followed for a mean of 3.0 years, men had a significantly higher rate (events/100
      patient-years) of recurrent venous thromboembolism than women for both venous
      thrombosis [rate ratio (RR) = 1.5, 95% confidence interval (CI):1.3-1.8] and
      pulmonary embolism [RR = 1.3, 95%CI:1.0-1.6]. Among men the recurrence rate did
      not vary significantly between the racial/ethnic groups (p > 0.05). However, the
      recurrence rate among Hispanic women with venous thrombosis was significantly
      higher than in Caucasian women (p < 0.001) and was comparable to the rate in men.
      Both Hispanic and African-American women with pulmonary embolism had a higher
      recurrence rate compared with Caucasian women (p < 0.02) that was comparable to
      the rate in men. We conclude that women in California had a 40% lower risk of
      recurrent venous thromboembolism compared to men. Rates were comparable among men
      of different races, but there were significant inter-racial differences among
      women, which also varied with the type of initial event. The effect of gender on
      the risk of recurrent venous thromboembolism can not be generalized because it
      varies between racial/ethnic groups and with the type of index event.

PMID- 16953267
TI  - Emerging anticoagulants for the treatment of venous thromboembolism.
AB  - Anticoagulant therapy is the cornerstone of treatment of venous thromboembolism
      (VTE). Such treatment is divided into two stages. Rapid initial anticoagulation
      is given to minimize the risk of thrombus extension and fatal pulmonary embolism,
      whereas extended anticoagulation is aimed at preventing recurrent VTE, thereby
      reducing the risk of postphlebitic syndrome. With currently available drugs,
      immediate anticoagulation can only be achieved with parenteral agents, such as
      heparin, low-molecular-weight heparin, or fondaparinux. Extended treatment
      usually involves the administration of vitamin K antagonists, such as warfarin.
      Emerging anticoagulants have the potential to streamline VTE treatment. These
      agents include idraparinux, a long-acting synthetic pentasaccharide that is given
      subcutaneously on a once-weekly basis, and new oral anticoagulants that target
      thrombin or factor Xa. This paper i) reviews the pharmacology of these agents,
      ii) outlines their potential strengths and weaknesses, iii) describes the results
      of clinical trials with these new drugs, and iv) identifies the evolving role of
      new anticoagulants in the management of VTE.

PMID- 16953268
TI  - Preeclampsia and pregnancy loss in women with a history of venous thromboembolism
      and prophylactic low-molecular-weight heparin (LMWH) during pregnancy.
AB  - Limited data are available regarding complications of pregnancy and pregnancy
      outcome under prophylaxis with low-molecular-weight heparin (LMWH) in women with
      a history of thromboembolism (TE). We retrospectively evaluated pregnancy
      complications in a cohort of 80 women. All had a history of TE (76 venous, two
      arterial and two venous and arterial) and received prophylactic LMWH during 86
      pregnancies. The rate of preeclampsia and stillbirth in these women was compared
      to that of a control group of 313 women without a history of TE and LMWH.
      Prophylaxis was started at a median of 10 weeks of gestation and usually
      continued until six weeks post partum. In 94% of the cases the outcome of
      pregnancy was favourable with a live birth. Four pregnancies (4.7%) ended in
      miscarriage. Two (2.3%) pregnancies were complicated by a thromboembolic event
      (one deep leg vein thrombosis and PRIND, respectively). One patient developed
      HELLP-syndrome. Severe preeclampsia occurred in three (3.8%) and stillbirth in
      one (1.3%) of the patients (n = 80), whereas this was the case in four (1.3%,
      odds ratio 3.01; 95% confidence interval (CI) 0.66-13.73, p = 0.15) and 10 (3.2%,
      OR = 0.38; 95% CI 0.05-3.04, p = 0.72) control women. Mean birth weight and
      standard deviation of infants was 3,160 +/- 930 g in patients and 3,300 +/- 540 g
      in controls (p = 0.11). We conclude that a favourable pregnancy outcome in women
      with a history of thromboembolism who use prophylactic LMWH during pregnancy can
      be expected. There was a trend towards a higher risk of preeclampsia, and these
      women should be carefully monitored for this complication.

PMID- 16953269
TI  - Type 2N von Willebrand disease due to compound heterozygosity for R854Q and a
      novel R763G mutation at the cleavage site of von Willebrand factor propeptide.
AB  - Type 2N von Willebrand disease (VWD) is characterized by a markedly decreased
      affinity of von Willebrand factor (VWF) for factorVIII (FVIII) and is caused by
      mutations in the D' or D3 domain of mature VWF. We now report a French patient
      with an atypical 2N VWD phenotype associating FVIII deficiency with plasmaVWF
      unable to bind FVIII (undetectableVWF:FVIIIB) but with an abnormal multimeric
      profile. This patient is heterozygous for both the frequent R854Q type 2NVWD
      mutation and a novel R763G mutation at the cleavage site between VWF propeptide
      and mature VWF. Four children of the patient displayed moderately decreased
      VWF:FVIIIB of plasma VWF and were heterozygous for either the R763G or the R854Q
      mutation. Children with the R763G mutation displayed the same abnormal multimeric
      profile as their father. Recombinant VWF (rVWF) expression studies performed in
      COS-7 cells showed that the R763G mutation subtly affects its multimeric profile
      and dramatically impairs its FVIII binding function. Furthermore, the
      characteristics of hybrid G763/Q854 rVWF resulting from cotransfection
      experiments were in agreement with the type 2N VWD diagnosis of the patient. We
      conclude that R763G is a new type 2N VWD mutation located in the VWF propeptide
      which alters the proteolytic processing of VWF and consequently its binding to
      FVIII.

PMID- 16953270
TI  - Amino acid regions 572-579 and 657-666 of the spacer domain of ADAMTS13 provide a
      common antigenic core required for binding of antibodies in patients with
      acquired TTP.
AB  - Antibodies directed against ADAMTS13 have been detected in the majority of
      patients with acquired thrombotic thrombocytopenic purpura (TTP). We have
      previously localized a major antigenic determinant within the spacer domain of
      ADAMTS13. To identify the amino acid residues of the spacer domain that are
      involved in binding of anti-ADAMTS13 antibodies, we constructed a series of
      fifteen hybrids (designated A-O) in which 5-10 amino acids of the spacer domain
      were exchanged for the corresponding region of ADAMTS1. Plasma from six patients
      with antibodies directed against the spacer domain was analyzed for reactivity
      with the ADAMTS13/ADAMTS1 chimeras. Exchange of amino acid residues 572-579
      (hybrid C) and 657-666 (hybrid M) completely abolished the binding of antibodies
      from all six patients analyzed. Regions 580-587 (D), 602-620 (G, H), 629-638 (J),
      and 667-767 (N) contributed to binding of antibodies from patients 2, 4, and 5
      (epitope present within regions CDGHJMN). Antibodies derived from patient 1
      required region 602-620 (G, H) for binding (CGHM-epitope). For antibodies of
      patient 3, residues 564-571 (B), 580-587 (D), and 629-638 (J) were required
      (BCDJM-epitope), whereas replacement of residues 602-610 (G) and 629-638 (J)
      greatly diminished binding of antibodies from patient 6 (CGJM-epitope). Despite
      the presumably polyclonal origin of the antibodies present in plasma of patients,
      our results suggest that residues 572-579 (C) and 657-666 (M) comprise a common
      antigenic core region that is crucial for binding of anti-ADAMTS13 antibodies.
      Other regions that spatially surround this antigenic core further modulate
      binding of antibodies to the spacer domain.

PMID- 16953271
TI  - Identification of a new truncated form and deamidation products of fibrinopeptide
      B released by thrombin from human fibrinogen.
AB  - Quantification of fibrinopeptides release is widely used to investigate
      fibrinogen activation, and standard chromatographic or capillary electrophoretic
      procedures are readily available. However, in the analyses of fibrinopeptide
      mixtures derived from the action of thrombin on human fibrinogen, a few
      unidentified peaks are usually present. The composition of these peaks was
      studied by reverse-phase HPLC/MS, revealing a single major anomalous peptide
      having a molecular mass of 1384.4. A further MS/MS analysis allowed the
      identification of this form, as a Nterminally truncated fibrinopeptide B (fpB)
      lacking the first two residues (pyroglutamic acid and glycine). This previously
      unidentified, relatively low-abundance form ( approximately 7%) has been found
      consistently in our fibrinopeptides preparations, and analysis of the parent
      Bbeta-chain suggest that it is likely present in circulating fibrinogen. In
      addition, deamidated forms of all fpB species (including desArgB), resulting from
      the conversion of asparagine to aspartic acid, were also identified. Overall,
      these previously unreported forms constitute a substantial amount of fpB (up to
      approximately 17% of the total), and should be taken into account for a reliable
      quantitative analysis of fpB release.

PMID- 16953272
TI  - Recombinant factor VIII and factor VIII-von Willebrand factor complex do not
      present danger signals for human dendritic cells.
AB  - Several lines of evidence have shown that antibody responses to coagulation
      factor VIII (FVIII) in patients with hemophilia A depend on the help of activated
      CD4(+) T cells. The primary activation of CD4(+) T cells requires interaction
      with mature dendritic cells (DCs) that present antigenic peptides in the context
      of MHC class II and express costimulatory molecules. Maturation of DCs requires
      danger signals provided by exogenous or endogenous stimuli such as pathogen
      derived products or inflammatory cytokines. We asked the question whether FVIII
      itself, FVIII complexed with von Willebrand factor (VWF) or thrombin-activated
      FVIII contain danger signals for human DCs that induce the upregulation of
      costimulatory molecules or the expression of proinflammatory cytokines necessary
      for effective activation of CD4(+) T cells. Human peripheral monocytes were
      differentiated into DCs. FVIII, thrombin-activated FVIII, VWF, VWF-FVIII,
      lipopolysaccharide (LPS), LPS + FVIII, LPS + VWF or LPS + FVIII-VWF were added
      either on day 0 or on day 5 of differentiation cultures. Differentiation markers,
      cytokines in cell culture supernatants and the capacity of DCs to stimulate
      autologous and allogeneic T cells were analysed after seven days of
      differentiation cultures. Our results indicate that neither FVIII, thrombin
      activated FVIII, VWF nor a complex of FVIII and VWF modulate the maturation of
      human DCs or their capacity to stimulate autologous or allogeneic T cells. We
      conclude that neither of these proteins present danger signals to human DCs.

PMID- 16953273
TI  - Amplified anticoagulant activity of tissue factor-targeted thrombomodulin: in
      vivo validation of a tissue factor-neutralizing antibody fused to soluble
      thrombomodulin.
AB  - Tissue factor (TF) exposure is a potent pro-thrombotic trigger that initiates
      activation of the coagulation cascade, while thrombomodulin (TM) is a potent
      anticoagulant protein that limits the extent of activation. Both TF neutralizing
      antibodies and soluble TM (sTM) are effective anticoagulants. We have developed a
      novel anticoagulant fusion protein, Ab(TF)-TM, by fusing a TFneutralizing single
      chain antibody, Ab(TF), to an active fragment of TM. Ab(TF)-TM is a novel
      anticoagulant targeting to sites of TF exposure with a dual mechanism of action.
      The Ab(TF) portion of the molecule inhibitsTF/factorVIIa mediated activation of
      FIX and FX, and the TM portion of the molecule acts as a cofactor for activation
      of protein C. In-vitro coagulation assays show that Ab(TF)-TM more potently
      inhibits TF-initiated coagulation (prothrombin time) than can its individual
      components, Ab(TF) (20-fold) and sTM (80-fold) alone, or in combination (10
      fold). In contrast, the potency of Ab(TF)-TM in the activated partial
      thromboplastin and thrombin clotting time assays was similar to sTM alone. In a
      rat model of disseminated intravascular coagulation (DIC), intravenous injection
      of a human TF-containing thromboplastin reagent (0.5 ml/kg) resulted in an
      immediate death in approximately 60% of the animals and a clinical score of
      approximately 2.5. Pre-injection of Ab(TF)-TM or Ab(TF) and sTM, given alone or
      in combination, showed dose-dependent efficacy. At a dose of 0.7 nmol/kg, Ab(TF)
      TM completely prevented death and reduced clinical scores by 79%, while
      neitherAb(TF) nor sTM, given alone or in combination, showed significant
      therapeutic effects. Calculated effective doses that reduced mortality by 50%
      relative to that in the control group (ED(50), nmol/kg) were 0.21 for Ab(TF)-TM,
      3.2 for an equimolar mixture of Ab(TF) and sTM, 4.3 for sTM and 20 for Ab(TF).
      Thus, Ab(TF)-TM presented 10- to 100-fold enhancement of the anticoagulant
      potency, relative to the ED(50) in Ab(TF) and sTM given either alone or in
      combination, in a rat DIC model.

PMID- 16953275
TI  - Haplotypes of the plasminogen activator gene associated with ischemic stroke.
AB  - Ischemic stroke (IS) is thought to be a multifactorial disorder associated with
      genetic backgrounds and environmental factors. In the circulating plasma, tissue
      plasminogen activator (tPA) catalyzes the reaction from plasminogen to plasmin.
      If there is a functional disability of tPA, induction of thrombosis and
      infarction disorders can occur. The aim of this study was to perform a haplotype
      based case-control study using single nucleotide polymorphisms (SNPs) in the
      human tPA gene, and to assess the association between the tPA gene and IS. We
      genotyped 182 IS individuals and 403 controls for five SNPs in the human tPA
      gene, rs7007329, rs732612, rs8178750, rs2020922, and rs4471024. Using these five
      SNPs, a haplotype-based case control study was performed. There were seven SNP
      combinations that exhibited significant differences in the overall distribution
      between the IS and control groups. Linkage disequilibrium analysis showed that
      the combination of rs7007329 and rs8178750 was useful in identification of the
      susceptibility haplotype. The frequency of the G-T haplotype at rs7007329
      rs8178750 was significantly higher in the IS group (1.2%) as compared to the
      control group (0.0%) (p = 0.003). Diplotype analysis also showed a significant
      association of the diplotype with the G-T haplotype at rs7007329-rs8178750
      (OR:11.4, 95%CI:1.32-97.9, p = 0.013). These results suggest that the G-T
      haplotype at rs7007329-rs8178750 of the tPA gene is a genetic marker for IS, and
      that tPA or a neighboring gene is a susceptibility gene for IS.

PMID- 16953274
TI  - Fibrinolytic efficacy of Amediplase, Tenecteplase and scu-PA in different
      external plasma clot lysis models: sensitivity to the inhibitory action of
      thrombin activatable fibrinolysis inhibitor (TAFI).
AB  - In this study, the in-vitro fibrinolytic efficacy of Tenecteplase, Amediplase and
      scu-PA was investigated in different external lysis models by measuring the lysis
      of human plasma clots after the addition of the plasminogen activators (PAs) to
      the surrounding plasma. The effect of TAFI was examined for each PA by
      neutralising TAFIa with potato carboxypeptidase inhibitor (PCI). The lytic
      efficacy of Amediplase was lower than that of Tenecteplase at low PA
      concentrations but slightly higher at therapeutic concentrations. The activity of
      scu-PA was clearly lower than that of either Tenecteplase or Amediplase. The TAFI
      system inhibited external clot lysis mediated by all the PAs when thrombomodulin
      was present in the model. In the therapeutic range (5-10 mug/ml) however, the
      TAFIa effect was negligible for both Amediplase and Tenecteplase. At lower PA
      concentrations the effect of TAFI on Amediplase was slightly stronger than that
      on Tenecteplase. Under static conditions the lysis rates were lower than with
      stirring. The role of TAFI was similar under both conditions. In conclusion, at
      therapeutic concentrations Amediplase was slightly more active than Tenecteplase
      and scu-PA under all conditions used. Therefore, Amediplase might possibly be a
      more potent thrombolytic agent at these concentrations and increase the efficacy
      of thrombolysis. The potential of TAFI for inhibiting thrombolytic therapy is
      probably low. However in conditions where the local PA concentrations are sub
      optimal TAFI might affect the lysis rate.

PMID- 16953276
TI  - Antibody profile and clinical course in primary antiphospholipid syndrome with
      pregnancy morbidity.
AB  - In women diagnosed as having category I primary obstetric antiphospholipid
      syndrome, clinical characteristics and the risk of subsequent thromboembolic
      events and further unsuccessful pregnancy has not been clearly documented. Women
      with unexplained obstetric complications and no definite autoimmune systemic
      diseases were tested for lupus anticoagulant (LA), IgG/IgM anticardiolipin (aCL)
      and IgG/IgM anti-human beta2-Glycoprotein I (abeta2GPI) antibodies and diagnosed
      as having primary antiphospholipid syndrome (APS) in classification category I on
      the basis of more than one laboratory criteria present in any combination.
      Characteristics at the time of diagnosis and risk factors for subsequent clinical
      events during a mean follow-up of 6.3 years were evaluated. Fifty-three of 600
      women studied were found to fulfil obstetric criteria and had more than one
      positive laboratory test at the time of diagnosis. All the women were aCL and
      abeta2GPI positive, and 16 were also LA positive. This latter group (triple
      positivity) had distinct features and had more frequently experienced previous
      thromboembolism (OR = 122.5, 95% CI 16-957, p < 0.001). They also had an
      increased rate of late pregnancy loss (OR = 16.2, 95%CI 0.9-292, p = 0.01), and a
      higher IgG abeta2GPI titer at diagnosis (median, 25(th) and 75(th) percentile
      were 118, 37-962, vs. 23, 18-32, respectively, p < 0.0001). During follow-up, the
      rate of thromboembolic events was significantly higher in the group of women with
      triple positivity and/ or previous thromboembolism (OR = 57.5, 95% CI 2.7-1160, p
      = 0.0004) which were the only independent predictors of TE in the multivariate
      model. Recurrent pregnancy loss took place in seven out of 47 women who had a new
      pregnancy. Triple positivity and/or previous thromboembolism were again the only
      independent markers (OR = 34.4, 95% CI 3.5-335.1, p = 0.003) of an unsuccessful
      new pregnancy. In conclusion, in primary APS with pregnancy morbidity in
      classification category I, quite different groups of patients may be identified
      on the basis of laboratory tests. Triple positivity and/or a history of
      thromboembolism predict new TE events and new unsuccessful pregnancies.

PMID- 16953277
TI  - Folic acid administration and antibodies against homocysteinylated proteins in
      subjects with hyperhomocysteinemia.
AB  - Growing evidence indicates that elevated total homocysteine (tHcy) levels can
      elicit autoimmune response in vivo. Antibodies against Nepsilon-Hcy-proteins have
      been shown to be associated with stroke and premature myocardial infarction. The
      aim of the current study was to investigate the effect of treatment with folic
      acid on anti-Nepsilon-Hcy-albumin and -hemoglobin antibodies. We recruited 20
      apparently healthy men and 12 male patients with documented coronary artery
      disease (CAD). All participants had plasma fasting tHcy levels >15 microM. At
      baseline, and after three and six months of treatment with folic acid 1 mg daily,
      we determined tHcy, serum folate and vitamin B12 levels, along with serum anti
      Nepsilon-Hcy-albumin and -hemoglobin IgG antibodies using the home-made
      immunoenzymatic assays. Both groups did not differ with regard to age, tHcy,
      folate, lipid profile, and CRP. The only significant difference between healthy
      subjects and CAD patients was levels of antibodies against Nepsilon-Hcy-albumin.
      As expected, folic acid administration led to significant decreases in tHcy and
      increases in folate levels in both groups. Levels of both anti-Nepsilon-Hcy
      albumin and -hemoglobin antibodies fell markedly following a three-month folic
      acid administration in healthy subjects, but not in CAD patients, without any
      changes at six months in either group. Folic acid administration resulted in a
      loss of significant correlations between tHcy and antibodies both following three
      and six months of the therapy in healthy subjects, in contrast to CAD patients.
      Carriers of the methylenetetrahydrofolate reductase (MTHFR) 677T allele with CAD
      had significantly higher levels of anti-Nepsilon-Hcy-albumin before and during
      folic acid administration as compared to healthy subjects. In conclusion, our
      findings suggest that Hcy-related autoimmune response is resistant to folic acid
      administration in CAD patients, while in healthy subjects reduced tHcy levels are
      associated with suppressed production of antibodies against Nepsilon-Hcyproteins.
      These observations might explain at least in part the failure of vitamin therapy
      to reduce the risk of cardiovascular events as recently reported.

PMID- 16953278
TI  - Psychological impact of testing for thrombophilic alterations.
AB  - We investigated the psychological impact of testing for the presence of
      thrombophilic alterations. The enrolled subjects received counseling from a
      physician before blood sampling and after receiving results, with a view to
      provide clear information about the aim of thrombophilia screening (TS).
      Participants were requested to complete a pre-test questionnaire during this
      interview and a post-test questionnaire 20 days after receiving the TS results.
      One hundred ninety-seven subjects completed the pretest questionnaire and 140/197
      (71.1%) returned the post-test one. The TS results were altered in 36 (25.7%,
      R506Q mutation n = 19; G20210A mutation n = 9; antithrombin deficiency n = 1; LAC
      phenomenon n = 4; hyperhomocysteinemia n = 3) and normal in 104 subjects. We
      assessed: perceived health status (PHS), state of anxiety, health fears,
      depressive reactions, moods, perceived well-being, and perceived daily-life
      stress. For both groups, both at pre- and post-test, none of the psychological
      variable scores showed significant worsening, regardless of whether TS resulted
      altered or normal. Anxiety significantly (p < or = 0.05) decreased at post-test
      in the altered group and a non-significant improvement in PHS after TS result
      communication was recorded in both groups. Age was an important factor in
      mediating psychological impact. In conclusion, diagnosis of thrombophilic
      alterations seems to be well accepted in the short term and TS should not be
      discouraged for potential adverse psychological effects. However, the
      psychological impact over a longer period of receiving altered results needs to
      be further investigated. The relationship between absence of adverse
      psychological reactions and quality of counseling program provided before and
      after TS should also be investigated.

PMID- 16953279
TI  - Identification of functional polymorphisms of the thromboxane A2 receptor gene in
      healthy volunteers.
AB  - Thromboxane A2 receptor (TP) is an important actor in vascular physiology and
      plays a crucial role in the platelet activation process. Genetic polymorphisms of
      the gene coding for the TP have been described, but their impacts on platelet
      function tests are unknown. The aim of this study was to investigate the
      relationship between genetic polymorphisms of the coding sequence of the TP gene
      and platelet function tests. We investigated 100 healthy volunteers twice, one
      week apart by performing platelet aggregation and secretion tests. We sequenced
      the coding region of the TP gene and confronted the genetic variants with the
      phenotypic results. We identified five single nucleotide polymorphisms (SNP); one
      of them, T1712C, replaces Leu by Pro at position 133 of the isoform beta of the
      TP. Homozygosity for the minor allele of the C795T, C924T or the G1686A SNP was
      associated with a decreased expression of CD62P when platelets were stimulated
      with the TP agonist U46619. As C795T and C924T have been linked to clinical
      disorders in which TxA2 plays a key role, the possible role of the G1686A and
      T1712C SNP should also be examined in selected diseases.

PMID- 16953280
TI  - A novel mechanism of transcriptional repression of p27kip1 through Notch/HRT2
      signaling in vascular smooth muscle cells.
AB  - Vascular smooth muscle cell (VSMC) proliferation occurs in vascular obstructive
      events such as atherosclerosis and restenosis. We previously showed that Notch
      receptors are induced in smooth muscle cells during vascular remodeling. Our goal
      was to determine the mechanisms employed by Notch signaling to regulate
      proliferation. Activation of Notch1 and Notch4 induced the VSMC-selective target
      genes HRT1 and HRT2, promoted cell cycle transit in smooth muscle cells, and led
      to loss of density-dependent growth inhibition. This was associated with a
      reduction in levels of the cyclin-dependent kinase inhibitor (cdk) p27(kip1).
      Over-expression of p27(kip1) resulted in a dose-dependent rescue of the Notch
      induced phenotype and exit from the cell cycle. In addition, HRT2 expression was
      sufficient to promote S-phase entry, and we demonstrate that HRT2 interacts
      directly with the p27(kip1) promoter to repress transcription. Transcriptional
      repression occurred within the approximately 774 bp minimal p27(kip1) promoter
      region and mutational analysis demonstrated that repression is largely dependent
      on a conserved class-C domain. Our data show that Notch signaling acts to promote
      a proliferative phenotype in VSMC by modulation of the G1/S-phase checkpoint. In
      addition, we define a novel mechanism by which the Notch effector, HRT2,
      interacts directly with the class-C domain of the p27(kip1) promoter, repressing
      its expression. These studies identify a novel transcriptional target of HRT2,
      and show that Notch effectors directly control cell cycle regulatory components.
      We suggest that this mechanism is relevant to hyperproliferative states in VSMC
      seen during vascular remodeling and repair.

PMID- 16953281
TI  - Antithrombin is as effective as heparin and hirudin to prevent formation of
      microvascular thrombosis in a murine model.
AB  - A recently published post-hoc analysis of a trial using high-dose antithrombin
      (AT) in septic patients (KyberSept) revealed significant reduction of lethality
      when no concomitant heparin was administered, whereas patients with the
      combination of heparin and AT did not benefit in terms of survival. Therefore, it
      seems feasible to study the capability of AT in prevention of microvascular
      thrombus formation to avoid concomitant application of heparin and AT. Using
      fluorescence microscopy and a light/dye-injury mouse ear model, the kinetics of
      thrombus formation were analyzed quantitatively in vivo upon single iv bolus of
      saline (control), heparin (100 IU/kg), hirudin (1 mg/kg) or AT (25, 50, 100 or
      250 IU/kg) (N = 7 animals per group each). In controls, light/dye-injury induced
      complete thrombotic occlusion in all arterioles and venules studied. Heparin and
      hirudin prevented thrombotic vessel occlusion in 62% and 43% of arterioles and
      11% and 28% of venules. AT-250 was found to be more effective than heparin and
      hirudin, because thrombus formation was completely banned in all arterioles and
      venules. AT-100 and AT-50 were also capable of significantly blocking thrombus
      formation in both arterioles and venules. In blood vessels, which finally
      clogged, the time for development of complete vessel occlusion was delayed after
      heparin, hirudin and AT-25, but in particular after AT-50 and AT-100. In
      conclusion, AT-mediated antithrombotic activity has been characterized in a model
      of phototoxicity-induced microvascular thrombosis formation, demonstrating that
      AT delays and prevents thrombus formation in arterioles and venules at least
      comparably effective as heparin and hirudin.

PMID- 16953282
TI  - Fibrinogen Nottingham II: a novel Bbeta Arg264gly substitution causing
      hypofibrinogenaemia.

PMID- 16953283
TI  - c.301C > T (p.Arg101Cys): a novel mutation in the thrombin-sensitive region of
      protein S associated with a dysfunctional protein.

PMID- 16953284
TI  - Acute coronary artery stent thrombosis following rapid renewal of functional
      platelets: implications for intensified antiplatelet therapy.

PMID- 16953285
TI  - The safety of co-administered continuous epidural analgesia and low-molecular
      weight heparin after major orthopedic surgery: assessment of a standardized
      patient management protocol.

PMID- 16953287
TI  - [Dilutional coagulopathy: development, diagnostic options and management].
AB  - When no fresh frozen plasma is available, acute major blood loss is compensated
      above all with crystalloids, colloids and red blood cell concentrates, meaning
      that all plasma clotting factors are diluted. Consumption coagulopathy is almost
      always accompanied by dilutional coagulopathy. Formulas for calculating critical
      blood loss and standard coagulation tests are often not helpful in the case of
      massive transfusion. On the other hand, systems suitable for point of care, such
      as thrombelastography, have important advantages. In the case of consumption and
      dilutional coagulopathy plasma coagulation is disturbed and critical values are
      first seen for fibrinogen. Not only is fibrin polymerization impaired by the
      bleeding-induced loss and dilution of fibrinogen, but also by interaction with
      artificial colloids, particularly hydroxyethyl starch preparations. Therapy of
      consumption and dilutional coagulopathy calls for fresh frozen plasma. If this is
      not available in sufficient quantity or within a reasonable time, coagulation
      factor concentrates must be used. Neither fresh frozen plasma therapy nor
      treatment with coagulation factor concentrates has been the subject of detailed
      clinical study. Further studies are needed to work out guidelines for coagulation
      management in the case of massive blood loss.

PMID- 16953288
TI  - [Possibilities and limitations of thrombelastometry/-graphy].
AB  - Thrombelastometry/-graphy provides information about clot strength and stability.
      Modified thrombelastometry/-graphy improved standardisation and diagnostic
      information using this system. Heparinase modified thrombelastometry/-graphy
      allows estimation of heparin. The introduction of FIBTEM on the ROTEM first
      allows a clear estimation of the plasmatic and the platelet component of clot
      strength, which may be of interest in managing haemostasis in perioperative
      setting. In this context the meaning of fibrinogen should be evaluated. As our
      clinical data show there is no predictive value of elevated D-dimers to
      hyperfibrinolysis in perioperative setting. However, thrombelastometry/-graphy do
      not deteckt disturbances in primary haemostasis such as von Willebrand Syndrom.
      The effect of acetylsalicylacid and clopidogrel do not have any influence on
      thrombelastometry/-graphy, as well. GPIIb/IIIa-Antagonists such as ReoPro may
      reduce clot strength at high dosis. A similar effect may be expected in severe M.
      Glanzmann. The correlation between coagulation time in thrombelastometry/-graphy
      (CT/r-value) to conventional coagulation may be low because of different
      activators used. The introduction of rotationthrombelastometry (ROTEM) provides a
      stable system suitable for bedside-monitoring.

PMID- 16953289
TI  - [Perioperative management of coagulation].
AB  - Guidelines of official societies for diagnosis and therapy of intraoperatively
      occurring hypocoagulability rely mainly on data of patients receiving whole blood
      transfusions. They recommend--provided that laboratory evaluation shows
      deficiency (values>1.5 fold normal)--administration of fresh frozen plasma,
      cryoprecipitate and platelet concentrates (platelet count<50,000 or
      <100,000/microl). This article describes the pathogenesis of coagulopathy in the
      light of the special intraoperative setting, emphasizes recent changes of blood
      component preparation, transfusion triggers, effects of volume therapy and
      challenges standard laboratory assays as reliable guide for intraoperative
      hemostatic therapy. The role of thrombelastographic monitoring is discussed as
      well as an alternative strategy to compensate deficiencies by the use of
      coagulation factor concentrates instead of or in addition to transfusion of FFP,
      a new concept which is illustrated by the presentation of an actual case report.

PMID- 16953290
TI  - [Fibrin monomer and factor XIII: a new concept for unexplained intraoperative
      coagulopathy].
AB  - Unexplained intraoperative coagulopathies continue to be a diagnostic and
      therapeutic dilemma. The pathophysiology behind unexplained intraoperative
      coagulopathies is of great variety and complexity (preexisting coagulopathies,
      dilutional coagulopathy, interactions of medications etc.). We have shown in
      prospective studies that patients undergoing elective surgery who develop
      "unexplained" intraoperative coagulopathies have significantly less FXIII per
      unit thrombin available at any point in time (i.e. already preoperatively) than
      patients without such coagulopathies. The consequence is a significant loss of
      clot firmness associated with an increase in intraoperative blood loss. Thus,
      these patients have less cross-linking capacity to begin with, which explains
      their preoperatively increased fibrin monomer concentration. The association of
      increased preoperative fibrin monomer and increased intraoperative blood loss was
      prospectively evaluated and confirmed in a separate clinical study. It is
      important to note that the acquired or (compared to the amount of thrombin
      generated) relative F. XIII deficiency in situations with surgical stress shows
      early clinical relevance (even if only mild to moderate changes are present);
      this differs from the experiences with patients with inborn FXIII deficiency,
      where a pronounced deficiency must be present to have clinically significant
      spontaneous bleeding. Patients undergoing elective surgery, without clinically
      obvious coagulopathy but increased preoperative fibrin monomer concentration (as
      a marker of decreased crosslinking capacity) are at risk for increased
      intraoperative blood loss. This new concept helps to explain the pathophysiology
      behind unexplained intraoperative coagulopathies and thus allows for
      corresponding treatment strategies. Further clinical studies for early detection
      and interventions in patients with such coagulopathies are necessary.

PMID- 16953291
TI  - [Safety of plasma-derived factor concentrates: an example of pharmacovigilance
      with fibrinogen and factor XIII-concentrate].
AB  - Elaborate measures for donor selection and the production of clotting factor
      concentrates have led to a high safety standard of these products. A multimodal
      approach to eliminate unwanted contents has been established by strict screening
      of possible donors and various inactivation procedures within the production
      process. The systematic registration of adverse events shows very few allergic
      and nonallergic reactions to plasma derived clotting factor concentrates. In none
      of the registered cases transmission of infections could be verified. The
      worldwide registration of such adverse events is not yet sufficiently
      established, since adequate structures are lacking in some countries. According
      to estimates, far less than half of occurring adverse events are registered in
      Germany. A European solution in the form of an official register is about to be
      introduced.

PMID- 16953292
TI  - [Modern anaesthesiological techniques and anticoagulation].
AB  - The variety of possibilities for medicamentous anticoagulation is constantly
      growing. Anesthesiologists and pain therapists are confronted with patients being
      treated with highly effective anticoagulatory or new antiaggregatory substances
      due to coronary heart disease, stroke or peripheral arterial disease. Especially
      these patients benefit from neuraxial blockades when undergoing cardiac surgery,
      revascularization surgery or amputations. The anaesthesiologist needs an overview
      concerning pharmacology, indications and side-effects of the anti- and
      procoagulatory substances and has to integrate this knowledge in the treatment
      concept to prevent haemorrhagic complications. This review depicts basics of
      coagulation, sites of action of currently applied anticoagulants and Austrian
      standards for performing modern central and peripheral nerve blocks under
      anticoagulatory medication. In general anaesthesia, too, the preoperative
      evaluation of preexisting anticoagulatory therapy is of high significance
      concerning the derivation of procedures for perioperative coagulation management.
      To prevent haemorrhagic complications in patients treated with anticoagulatory
      agents, recommendations concerning the following questions are given: time
      intervals between the application of anticoagulatory substances and punction,
      removal of catheters or general anaesthesia and operation; the choice and
      performance of the locoregional anaesthesiologic method and intraoperative
      coagulation analysis method; reversion of anticoagulation in acute situations.

PMID- 16953293
TI  - [Coagulation management in major trauma].
AB  - In trauma associated coagulopathy, the initial treatment consists of hypothermia
      and acidosis have to be treated aggressively. Already in in the emergency room,
      fibrinogen deficiency can be detected frequently, in addition, colloids interfere
      with fibrin polymerisation. Under these aspects, the early administration of
      fibrinogen seems to be justified. Depleted coagulation factors can be substituted
      with PPSB and/or fresh frozen plasma, while in view of a risk of infection,
      retaining administration of platelet concentrates is indicated. The potential of
      using haemostatic agents like antifibrinolytics and DDAVP for this indication is
      only supported by few studies, although in individual cases it may be very
      helpful. The administration of recombinant FVIIa could not achieve sustainable
      amelioration of the outcome of trauma patients in a randomised controlled trial.
      Raising inhibitors of coagulation (antithrombin) simultaneously to
      antihaemorragic therapy is being discussed, but seems not reasonable in the acute
      phase of a life-threatening haemorrage.

PMID- 16953294
TI  - [Haemorrhagic complications in obstetrics].
AB  - The instability of the gestational and puerperal equilibrium of haemostasis is
      affected by a shift of primary and plasmatic haemostasis in a procoagulatory
      direction, whereas the regulation mechanism of the fibrinolytic system can easily
      cause disproportional peri- and postpartal reaction leading to massive
      haemorrhage. Peripartal injuries or an atonic uterus can lead to massive
      haemorrhage and cause a classic haemorrhagic coagulopathy. Complications like
      amniotic fluid embolism, puerperal sepsis, eclampsia or HELLP syndrome can lead
      through DIC to rapidly developing and possibly fulminant hyperfibrinolysis. This
      article depicts different forms of haemorrhage in the peripartal situation, their
      particular pathologies and specific possibilities for management. A case study
      demonstrates the diagnostic and therapeutic options in the case of eclampsia with
      early abruption of placenta.

PMID- 16953295
TI  - [Coagulation management during liver transplantation].
AB  - In the course of liver transplantation many patients develop coagulation and
      bleeding disorders. On the other hand, some patients suffer thromboembolic events
      in the perioperative period with sometimes fatal outcome. For this reason, in
      1999 we changed our coagulation management for liver transplantation and
      abolished the routine prophylaxis with antifibrinolytic drugs. In this context we
      implemented the ROTEM system (Pentapharm GmbH, Munich) in our perioperative point
      of-care coagulation management. From 2000 to 2005, we analysed more than 18,000
      ROTEM measurements in the context of 642 liver transplantations. Prophylactic
      administration of antifibrinolytic drugs was only done in patients with fulminant
      liver failure or if MCF in ExTEM<or=35 mm at the beginning of surgery. In the
      other patients hyperfibrinolysis was detected in 60% during the operation.
      However, therapy with an antifibrinolytic drug only was necessary in 40% of the
      patients. Our experience is summarised in an algorithm for ROTEM-based
      perioperative coagulation management for liver transplantation.

PMID- 16953296
TI  - [Bleeding after cardiac surgery: the role of recombinant factor VIIa].
AB  - Cardiac surgery carries a remarkable risk of blood loss requiring transfusion of
      blood products. Moreover, severe bleeding necessitating reoperation occurs in 3
      5% of patients according to international studies. These patients face a
      significantly higher morbidity and mortality. This underscores the need for a
      safe and effective haemostatic therapy, which may significantly improve the
      outcome. Recombinant activated factor VII is approved for haemophiliacs with
      inhibitors and patients with thrombasthenia Glanzmann and factor VII deficiency.
      In the proceeding years a series of articles has been published reporting the
      successful and safe therapy of refractory bleeding after cardiac surgery. This
      review focuses at presenting the pathophysiological alterations of the
      haemostatic system related to the cardiopulmonary bypass. These alterations are
      thought to explain the high risk of bleeding after cardiopulmonary bypass.
      Furthermore, the use of rFVIIa in paediatric and adult cardiac surgery is
      reviewed and critically discussed.

PMID- 16953297
TI  - Recombinant neural protein PrP can bind with both recombinant and native
      apolipoprotein E in vitro.
AB  - The most essential and crucial step during the pathogenesis of transmissible
      spongiform encephalopathy is the conformational change of cellular prion protein
      (PrP(C)) to pathologic isoform (PrP(Sc)). A lot of data revealed that caveolae
      like domains (CLDs) in the cell surface were the probable place where the
      conversion of PrP proteins happened. Apolipoprotein E (ApoE) is an apolipoprotein
      which is considered to play an important role in the development of Alzheimer's
      disease and other neurodegenerative diseases by forming protein complex through
      binding to the receptor located in the clathrin-coated pits of the cell surface.
      In this study, a 914-bp cDNA sequence encoding human ApoE3 was amplified from
      neuroblastoma cell line SH-SY5Y. Three human ApoE isomers were expressed and
      purified from Escherichia coli. ApoE-specific antiserum was prepared by
      immunizing rabbits with the purified ApoE3. GST/His pull-down assay,
      immunoprecipitation and ELISA revealed that three full-length ApoE isomers
      interact with the recombinant full-length PrP protein in vitro. The regions
      corresponding to protein binding were mapped in the N-terminal segment of ApoE
      (amino acid 1-194) and the N-terminal of PrP (amino acid 23-90). Moreover, the
      recombinant PrP showed the ability to form a complex with the native ApoE from
      liver tissues. Our data provided direct evidence of molecular interaction between
      ApoE and PrP. It also supplied scientific clues for assessing the significance of
      CLDs on the surface of cellular membrane in the process of conformational
      conversion from PrP(C) to PrP(Sc) and probing into the pathogenesis of
      transmissible spongiform encephalopathy.

PMID- 16953298
TI  - Characterization of genes associated with different phenotypes of human bladder
      cancer cells.
AB  - To identify genes associated with morphological phenotypes of human bladder
      transitional cell carcinoma, we used suppression subtractive hybridization (SSH)
      to create a subtractive cDNA library of two established cell lines, BLZ-211 and
      BLS-211, derived from a patient with transitional cell carcinoma of the bladder,
      then to screen for differentially expressed genes. Real-time reverse
      transcription-polymerase chain reaction was used to further confirm the selected
      differentially expressed genes. Forward and reverse subtractive cDNA libraries
      yielded 168 and 305 putative clones, and among them more than 90% contained the
      inserts. After differential screening, 36 different transcripts were obtained
      from 64 cDNA clones of a forward and reverse subtraction library. Among them, 17
      were identified as known genes by homology, for example, Vimentin, Keratin7, DDH
      and UCH-L1. The remaining 19 were unknown expressed genes, and were collected as
      new expressed sequence tags by the GenBank dbEST database. Their function will be
      studied further. Thus, SSH appears to be a useful technique for identifying
      differentially expressed genes between cell lines or clones. Our results, as
      revealed by SSH, also suggest that differences in gene expression of cytoskeletal
      proteins might contribute to the different morphologies in BLZ-211 and BLS-211
      cells.

PMID- 16953300
TI  - Characterization of Nocardia plasmid pXT107.
AB  - Nocardia, Rhodococcus and Streptomyces, all members of the actinomycetes family,
      are Gram-positive eubacteria with high G+C content and able to form mycelium. We
      report here a newly identified plasmid pXT107 of Nocardia sp. 107, one of the
      smallest circular plasmids found in Nocardia. The complete nucleotide sequence of
      pXT107 consisted of 4335 bp with 65% G+C content, and encoded one replication
      extragenic palindromic (Rep) and six hypothetical proteins. The Rep, double
      strand origin and single-strand origin of pXT107 resembled those of typical
      rolling-circle-replication plasmids, such as pNI100 of Nocardia, pRE8424 of
      Rhodococcus and pIJ101 of Streptomyces. The Escherichia coli-Nocardia shuttle
      plasmid pHAQ22, containing the rep gene of pXT107, is able to propagate in
      Nocardia but not in Streptomyces.

PMID- 16953299
TI  - Six specific lysine residues are crucial in maintaining the structure and
      function of soluble manganese stabilizing protein.
AB  - When manganese stabilizing protein (MSP) was treated with 0.5 mM N-succinimidyl
      propionate (NSP), the rebinding ability and oxygen-releasing capabilities of the
      modified MSP were not altered, in spite of changes of MSP surface Lys residues.
      Furthermore, far-ultraviolet circular dichroism and intrinsic fluorescence
      spectra analysis revealed that 0.5 mM NSP-modified MSP retained most of its
      native secondary and tertiary structure. Mapping of the sites of NSP modification
      by Staphylococcus V(8) protease digestion of the modified protein, as well as
      analysis by matrix-assisted laser desorption ionization-time of flight mass
      spectrometry, indicated that seven Lys residues were modified. The results
      suggested that these residues are not absolutely essential to the structure and
      function of MSP. However, when the NSP concentration was increased to 4 mM, the
      modified MSP was unable to bind photosystem II and completely lost its
      reactivating capability. Both far-ultraviolet circular dichroism and intrinsic
      fluorescence spectra analysis revealed a clear conformational change in MSP after
      4 mM NSP treatment, suggesting that some Lys residues are involved in maintaining
      the structure and function of MSP. Analysis by matrix-assisted laser desorption
      ionization-time of flight mass spectrometry indicated that another six Lys
      residues, namely Lys20, Lys101, Lys196, Lys207, Lys130 (or Lys137) and Lys66 (or
      Lys76), were modified by 4 mM NSP. Therefore, these six Lys residues are crucial
      in maintaining the structure and function of soluble MSP.

PMID- 16953301
TI  - Preparation of monoclonal antibodies against human ventricular myosin light chain
      1 (HVMLC1) for functional studies.
AB  - Using purified recombinant human ventricular myosin light chain 1 (HVMLC1) as the
      antigen, three monoclonal antibodies, designated C8, C9 and B12, were prepared.
      Immunoblot experiments demonstrated that all monoclonal antibodies could react
      with the ventricular myosin light chain 1 isolated from different sources, such
      as human, rat or pig. It was also demonstrated that C8 was directed against the
      NN part of the N-fragment (amino acid 1-40) of HVMLC1, and both C9 and B12
      against the C-fragment (amino acid 99-195). The affinity constants of C8, C9 and
      B12 were 3.20 x 10(8), 8.600 x 10(7) and 1.770 x 10(8) M(-1), respectively,
      determined by non-competitive ELISA. The isotype of B12 was determined as IgG2a,
      whereas the isotype of both C8 and C9 were IgG1. In the presence of C9 or B12,
      the actin-activated Mg(2+)ATPase activity of myosin was greatly inhibited, but
      there was almost no effect on the Mg(2+) ATPase activity for C8. B12 and C9 also
      inhibited the superprecipitation of porcine cardiac native actomyosin (myosin B)
      and reconstituted actomyosin, but C8 did not. The results indicate that all three
      monoclonal antibodies could bind the intact myosin molecule, but B12 and C9 might
      more easily react with epitopes located in the C-fragment of HVMLC1. The
      inhibitory effects of B12 and C9 on ATPase activity and superprecipitation assays
      show that light chain 1, particularly the C-fragment domain, is involved in the
      modulation of the actin-activated Mg(2+) ATPase activity of myosin and, as a
      consequence, plays an essential role in the interaction of actin and myosin.

PMID- 16953302
TI  - Purification and characterization of alginate lyase from marine Vibrio sp. YWA.
AB  - Extracellular alginate lyase secreted by marine Vibrio sp. YWA, isolated from
      decayed Laminaria japonica, was purified by a combination of ammonium sulfate
      precipitation and diethylaminoethyl-Sephacel column chromatography. The results
      show that the molecular mass of alginate lyase was approximately 62.5 kDa, with
      an optimal pH and temperature at pH 7.0 and 25 degrees C, respectively. K(m) was
      approximately 72.73 g/L. The activity of the enzyme was enhanced by EDTA and
      Zn(2+), but inhibited by Ba(2+). The substrates specificity analysis shows that
      it was specific for hydrolyzing poly-beta-D-1,4-mannuronate in alginate.

PMID- 16953303
TI  - Gene expression of ornithine decarboxylase in lung cancers and its clinical
      significance.
AB  - Lung cancer is one of the most lethal cancers in China because of its high
      incidence and high mortality. Ornithine decarboxylase (ODC), an important enzyme
      in polyamine biosynthesis, is increased in cancer cells. Some chemotherapeutic
      agents aimed at reducing ODC expression show inhibitory effects on cancer cell
      growth, so ODC can be useful in gene diagnosis and gene therapy of cancers. In
      this study, we examined the effect of antisense ODC on lung cancer cells. A-549
      cells were infected with rAd-ODC/Ex3as, a recombinant adenovirus containing the
      cytomegalovirus promoter, green fluorescent protein gene and 120 bp antisense
      ODC. The cell cycle was evaluated by flow cytometry. A nude mouse xenograft model
      was used in the tumorigenicity test. Reverse transcription-polymerase chain
      reaction, Western blot and immunohistochemistry were used to study the
      expressions of ODC on lung cancers. It was found that the growth of cells
      infected with rAd-ODC/Ex3as was substantially inhibited and cells were arrested
      at G1 phase. Cells infected with rAd-ODC/Ex3as can suppress tumor formation in a
      nude mouse xenograft model. The expression of ODC mRNA and ODC protein levels in
      lung cancer tissues was significantly higher than that in normal tissues
      (P<0.05), which correlated significantly with the stage of lung cancer (P<0.05).
      This study suggested that rAd-ODC/Ex3as has antitumor activity in human lung
      cancer cells. The ODC gene might play an important role in lung cancer and the
      overexpression of ODC might be related to the occurrence and development of lung
      cancer.

PMID- 16953304
TI  - Atomic force microscopy-based cell nanostructure for ligand-conjugated quantum
      dot endocytosis.
AB  - While it has been well demonstrated that quantum dots (QDs) play an important
      role in biological labeling both in vitro and in vivo, there is no report
      describing the cellular nanostructure basis of receptor-mediated endocytosis.
      Here, nanostructure evolution responses to the endocytosis of transferrin (Tf)
      conjugated QDs were characterized by atomic force microscopy (AFM). AFM-based
      nanostructure analysis demonstrated that the Tf-conjugated QDs were specifically
      and tightly bound to the cell receptors and the nanostructure evolution is highly
      correlated with the cell membrane receptor-mediated transduction. Consistently,
      confocal microscopic and flow cytometry results have demonstrated the specificity
      and dynamic property of Tf-QD binding and internalization. We found that the
      internalization of Tf-QD is linearly related to time. Moreover, while the
      nanoparticles on the cell membrane increased, the endocytosis was still very
      active, suggesting that QD nanoparticles did not interfere sterically with the
      binding and function of receptors. Therefore, ligand-conjugated QDs are
      potentially useful in biological labeling of cells at a nanometer scale.

PMID- 16953305
TI  - Differentially expression of Tua1, a tubulin-encoding gene, during flowering of
      tea plant Camellia sinensis (L.) O. Kuntze using cDNA amplified fragment length
      polymorphism technique.
AB  - The complementary DNA (cDNA) amplified fragment length polymorphism technique was
      used to isolate transcript-derived fragments corresponding to genes involved in
      the flowering of tea plant. Comparative sequence analysis of an approximately 300
      bp differential fragment amplified by primer combination E11M11 revealed 80%-84%
      similarity to the corresponding part of an a-tubulin gene of other species. The
      complete cDNA sequence of this a-tubulin was cloned by the rapid amplification of
      cDNA ends technique; its full length is 1537 bp and contains an open reading
      frame of 450 amino acid residues with two N-glycosylation sites and four protein
      kinase C phosphorylation sites. The deduced amino acid sequences did show
      significant homology to the a-tubulin from other plants that has been reported to
      be a pollen-specific protein and could be correlated with plant cytoplasm-nucleus
      interacted male sterility. We named this complete cDNA Tua1. The nucleotide and
      amino acid sequence data of Tua1 have been recorded in the GenBank sequence
      database. This Tua1 gene was cloned into the pET-32a expression system and
      expressed in Escherichia coli BL21trxB(DE3). The molecular weight of expressed
      protein was deduced to be approximately 49 kDa. Western blot analysis was used to
      identify the temporal expression of Tua1 in tea plant. Further studies of the
      effect of Tua1 protein on pollen tube growth indicated the Tua1 solution
      obviously promoted the growth of tea pollen tube.

PMID- 16953306
TI  - Expression, purification and anti-tumor activity of curcin.
AB  - Curcin, purified from the seeds of Jatropha curcas, can be used as a cell-killing
      agent. Understanding the anti-tumor activity of the recombinant protein of curcin
      is important for its application in clinical medicine. The segment encoding the
      mature protein of curcin was inserted into Escherichia coli strain M15, and the
      recombinant strain was induced to express by isopropyl-beta-D
      thiogalactopyranoside at a concentration of 0.5 mM. The recombinant protein was
      expressed in the form of inclusion bodies and purified by Ni-NTA affinity
      chromatography. The target protein was incubated with the tumor cells at
      different concentrations for different times and the results demonstrated that
      the target protein could inhibit the growth of tumor cells (NCL-H446, SGC-7901
      and S180) at 5 microg/ml.

PMID- 16953307
TI  - Low replication and variability of HBV pre-core in concomitant infection with
      hepatitis B and hepatitis C viruses.
AB  - In an attempt to define the virological profile of HBV in HCV co-infection, we
      analysed the viral load, the infecting genotype, and the mutational pattern of
      the HBV pre-core region (pre-C), which is involved in viral encapsidation and DNA
      replication. Eighty-six patients were studied: 32 with serological HBV/HCV-1b co
      infection (group BC), 32 infected by HBV alone (group B), and 22 by HCV-1b alone
      (group C). Sequence analysis of the HBV pre-S and pre-C regions identified
      genotypes and mutational patterns. The HBV viral load was significantly lower in
      group BC than in group B (p < 0.001), and the distribution of HBV pre-C mutations
      showed a higher prevalence of wild type in concomitant infection than in the
      control group (p < 0.006). The predominant HBV infecting strain was genotype D in
      both the BC (96%) and B (87%) groups. No difference was observed in HCV viremia
      levels between the two groups, whereas in HBV/HCV infection, the low levels of
      circulating HBV were closely associated with the low degree of variability of pre
      C domain (p = 0.005). In conclusion, in HBV/HCV infection, the virological
      pattern was characterised by the dominance of HCV associated with lower HBV
      replication capacity and decreased emergence of HBV pre-C variants.

PMID- 16953309
TI  - Intraspecific variation of flower colour and its distribution within a sea
      lavender, Limonium wrightii (Plumbaginaceae), in the northwestern Pacific
      Islands.
AB  - Differentiation of flower colour is thought to be one of the most important
      factors promoting plant speciation. We describe the intraspecific variation of
      flower colour and its distribution in Limonium wrightii. We conducted a survey on
      36 islands in the northwestern Pacific and discriminated six morphs of flower
      colour variation. Two flower colour morphs, pink and yellow, were most frequently
      observed, and their geographical distributions were basically allopatric. These
      two morphs were in contact in a narrow zone on Okinoerabu Island, located in the
      middle region of the Ryukyu Archipelago. In addition, orange, white, and ivory
      flower morphs were also found in this zone. The geographical distribution of pink
      and yellow morphs showed a "leapfrog" pattern; the distribution of pink flowers
      was divided into two areas, intercalated by the distribution of the yellow flower
      morph. The orange morph may have resulted from hybridization between the pink and
      yellow flower morphs.

PMID- 16953308
TI  - International Continence Society 2002 terminology report: have urogynecological
      conditions (diagnoses) been overlooked?

PMID- 16953310
TI  - Non-destructive analysis of museum objects by fibre-optic Raman spectroscopy.
AB  - Raman spectroscopy is a versatile technique that has frequently been applied for
      the investigation of art objects. By using mobile Raman instrumentation it is
      possible to investigate the artworks without the need for sampling. This work
      evaluates the use of a dedicated mobile spectrometer for the investigation of a
      range of museum objects in museums in Scotland, including antique Egyptian
      sarcophagi, a panel painting, painted surfaces on paper and textile, and the
      painted lid and soundboard of an early keyboard instrument. The investigations of
      these artefacts illustrate some analytical challenges that arise when analysing
      museum objects, including fluorescing varnish layers, ambient sunlight, large
      dimensions of artefacts and the need to handle fragile objects with care.
      Analysis of the musical instrument (the Mar virginals) was undertaken in the
      exhibition gallery, while on display, which meant that interaction with the
      public and health and safety issues had to be taken into account. Experimental
      set-up for the non-destructive Raman spectroscopic investigation of a textile
      banner in the National Museums of Scotland.

PMID- 16953311
TI  - Application of double-spike isotope dilution for the accurate determination of
      Cr(III), Cr(VI) and total Cr in yeast.
AB  - A method is presented for the simultaneous determination of Cr(III) and Cr(VI) in
      yeast using species-specific double-spike isotope dilution (SSDSID) with anion
      exchange liquid chromatography (LC) separation and sector field inductively
      coupled plasma mass spectrometric (SF-ICP-MS) detection. Total Cr is quantitated
      using ID SF-ICP-MS. Samples were digested on a hot plate at 95+/-2 degrees C for
      6 h in an alkaline solution of 0.5 M NaOH and 0.28 M Na2CO3 for the determination
      of Cr(III) and Cr(VI), whereas microwave-assisted decomposition with HNO3 and
      H2O2 was used for the determination of total Cr. Concentrations of 2,014+/-16,
      1,952+/-103 and 76+/-48 mg kg-1 (one standard deviation, n=4, 3, 3), respectively
      were obtained for total Cr, Cr(III) and Cr(VI) in the yeast sample. Significant
      oxidation of Cr(III) to Cr(VI) (24.2+/-7.6% Cr(III) oxidized, n=3) and reduction
      of Cr(VI) to Cr(III) (37.6+/-6.5% Cr(VI) reduced, n=3) occurred during alkaline
      extraction and subsequent chromatographic separation at pH 7. Despite this
      significant bidirectional redox transformation, quantitative recoveries for both
      Cr(III) and Cr(VI) were achieved using the SSDSID method. In addition, mass
      balance between total Cr and the sum of Cr(III) and Cr(VI) concentrations was
      achieved. Method detection limits of 0.3, 2 and 30 mg kg-1 were obtained for
      total Cr, Cr(VI) and Cr(III), respectively, based on a 0.2-g sub-sample.

PMID- 16953312
TI  - Quo vadis? Leading the way with the younger generation of scientists.

PMID- 16953313
TI  - Optimization of DNA-tagged liposomes for use in microtiter plate analyses.
AB  - Dye-encapsulating unilamellar DNA oligonucleotide-tagged liposomes were prepared
      and characterized for use as signal-enhancing reagents in a microtiter plate
      sandwich-hybridization analyses of single-stranded RNA or DNA sequences. The
      liposomes were synthesized using the reversed-phase evaporation method and tagged
      with DNA oligonucleotides by adding cholesteryl-modified DNA reporter probes to
      the initial lipid mixture. Liposomes were prepared using probe coverages of
      0.0013-0.103 mol% of the total lipid input, several hydrophobic and poly(ethylene
      glycol)-based spacers between the cholesteryl anchor and the probe, and liposome
      diameters ranging from 200 nm to 335 nm. Their signal enhancement functionality
      was compared by using them in microtiter plate sandwich-hybridization assays for
      the detection of single-stranded DNA sequences. In these assays, an optimal
      reporter probe concentration of 0.103 mol%, a liposome diameter of 274 nm, and a
      phospholipid concentration of 0.3 mM were found. The length between the
      cholesteryl anchor and the probe was optimal when a spacer composed of
      TEG+(CH2O)3 was used. Under optimal conditions, a detection limit of 0.5 nM for a
      truncated synthetic DNA sequence was found with a coefficient of variation of
      4.4%. A 500-fold lower limit of detection using fluorescence was found using
      lysed dye-encapsulating liposomes versus a single fluorescein-labeled probe.
      Finally, when this method was applied to the detection of atxA RNA extracted from
      E.coli SG12036-pIu121 and amplified using NASBA, a minimum extracted
      concentration of RNA of 1.1x10(-7) microg/microL was found.

PMID- 16953314
TI  - Determination of parathion in biological fluids by means of direct solid-phase
      microextraction.
AB  - A new and simple procedure for the determination of parathion in human whole
      blood and urine using direct immersion (DI) solid-phase microextraction (SPME)
      and gas chromatography/mass spectrometry (GC/MS) is presented. This technique was
      developed using only 100 microL of sample, and ethion was used as internal
      standard (IS). A 65-microm Carbowax/divinylbenzene (CW/DVB) SPME fibre was
      selected for sampling, and the main parameters affecting the SPME process such as
      extraction temperature, adsorption and desorption time, salt addition, agitation
      and pH effect were optimized to enhance the sensitivity of the method. This
      optimization was also performed to allow the qualitative determination of
      parathion's main metabolite, paraoxon, in blood. The limits of detection and
      quantitation for parathion were 3 and 10 ng/mL for urine and 25 and 50 ng/mL for
      blood, respectively. For paraoxon, the limit of detection was 50 ng/mL in blood.
      The method showed linearity between the LOQ and 50 microg/mL for both matrices,
      with correlation coefficients ranging from 0.9954 to 0.9999. Precision and
      accuracy were in conformity with the criteria normally accepted in bioanalytical
      method validation. The mean absolute recoveries were 35.1% for urine and 6.7% for
      blood. Other parameters such as dilution of sample and stability were also
      validated. Its simplicity and the fact that only 100 microL of sample is required
      to accomplish the analysis make this method useful in forensic toxicology
      laboratories to determine this compound in intoxications, and it can be
      considered an alternative to other methods normally used for the determination of
      this compound in biological media.

PMID- 16953315
TI  - Development of a competitive ELISA for the quantification of F5 conjugate in HER2
      targeted STEALTH immunoliposome doxorubicin in plasma samples.
AB  - HER2 (human epidermal growth factor receptor 2, erbB2, or neu) is overexpressed
      by a large number of tumor types and has been identified as an important target
      for cancer therapy. F5 is a single-chain human antibody fragment that recognizes
      HER2 receptor and is covalently conjugated to PEGylated lipid to form F5
      conjugate (F5CG) in the product HER2 targeted STEALTH immunoliposome doxorubicin.
      Here we described the method development of a competitive enzyme-linked
      immunosorbent assay (ELISA) for the determination of total concentration of F5
      conjugate in plasma samples. The method involved the biotinylation of F5CG,
      detergent treatment of plasma sample to solubilize F5CG into monomeric form, and
      competitive ELISA for solubilized F5CG competitively binding to anti-F5CG
      antibody with biotinylated F5CG for the determination of total F5CG in plasma.
      The detection range of this method was from 0.2 ng/mL to 125 ng/mL for F5CG in
      plasma. The lower limit of quantification (LLOQ) was 0.2 ng/mL. This method was
      established and used for the measurement of F5CG concentration to provide
      information about F5CG circulation after the administration of immunoliposome in
      preclinical studies.

PMID- 16953316
TI  - Beyond quorum sensing: the complexities of prokaryotic parliamentary procedures.
AB  - Bacterial quorum-sensing regulatory systems can be summarized in a simple model
      wherein an autoinducer molecule accumulates in cultures and stimulates regulatory
      changes in gene expression upon reaching a critical threshold concentration.
      Although quorum sensing was originally thought to be an isolated phenomenon
      governing the regulation of a handful of processes in only a few bacteria, it is
      now considered to be a widespread mechanism for coordinating bacterial gene
      expression. Over decades of research, investigations of autoinducer-mediated
      regulation have revealed that these systems are far more complicated than
      originally appreciated, and such discoveries have accelerated recently with the
      application of molecular and genomic tools. The focus of this review is to
      highlight recent advances describing complexities that go beyond the simple model
      of quorum sensing. These complexities include the regulation of autoinducer
      production and degradation, the presence of multiple quorum-sensing systems in
      individual bacteria that regulate diverse genes, often in coordination with other
      regulatory elements, and the influence of interorganismal interactions on quorum
      sensing.

PMID- 16953317
TI  - Synchronous fluorescence spectroscopy for quantitative determination of virgin
      olive oil adulteration with sunflower oil.
AB  - Adulteration of extra virgin olive oil with sunflower oil is a major issue for
      the olive oil industry. In this paper, the potential of total synchronous
      fluorescence (TSyF) spectra to differentiate virgin olive oil from sunflower oil
      and synchronous fluorescence (SyF) spectra combined with multivariate analysis to
      assess the adulteration of virgin olive oil are demonstrated. TSyF spectra were
      acquired by varying the excitation wavelength in the region 270-720 nm and the
      wavelength interval (Deltalambda) in the region from 20 to 120 nm. TSyF contour
      plots for sunflower, in contrast to virgin olive oil, show a fluorescence region
      in the excitation wavelength range 325-385 nm. Fifteen different virgin olive oil
      samples were adulterated with sunflower oil at varying levels (0.5-95%) resulting
      in one hundred and thirty six mixtures. The partial least-squares regression
      model was used for quantification of the adulteration using wavelength intervals
      of 20 and 80 nm. This technique is useful for detection of sunflower oil in
      virgin olive oil at levels down to 3.4% (w/v) in just two and a half minutes
      using an 80-nm wavelength interval.

PMID- 16953318
TI  - Improvement of HS-SPME for analysis of volatile organic compounds (VOC) in water
      samples by simultaneous direct fiber cooling and freezing of analyte solution.
AB  - The sensitivity and precision of headspace solid-phase micro extraction (HS-SPME)
      at an analyte solution temperature (T (as)) of +35 degrees C and a fiber
      temperature (T (fiber)) of +5 degrees C were compared with those for HS-SPME at T
      (as) and T (fiber) of -20 degrees C for analysis of the volatile organic
      compounds benzene, 1,1,1-trichloroethane, trichloroethylene, toluene, o-xylene,
      ethylbenzene, m/p-xylene, and tetrachloroethylene in water samples. The effect of
      simultaneous fiber cooling and analyte solution freezing during extraction was
      studied. The compounds are of different hydrophobicity, with octanol/water
      partition coefficients (Kow) ranging from 126 and 2511. During a first set of
      experiments the polydimethylsiloxane (PDMS) SPME fiber was cooled to +5 degrees C
      with simultaneous heating of the aqueous analyte solution to +35 degrees C.
      During a second set of experiments, both SPME fiber holder and samples were
      placed in a deep freezer maintained at -20 degrees C for a total extraction time
      of 30 min. After approximately 2 min the analyte solution in the vial began to
      freeze from the side inwards and from the bottom upwards. After approximately 30
      min the solution was completely frozen. Analysis of VOC was performed by coupling
      HS-SPME to gas chromatography-mass spectrometry (GC-MS). In general, i.e. except
      for tetrachloroethylene, the sensitivity of HS-SPME increased with increasing
      compound hydrophobicity at both analyte solution and fiber temperatures. At T
      (as) of +35 degrees C and T (fiber) of +5 degrees C detection limits of HS-SPME
      were 0.5 microg L(-1) for benzene, 1,1,1-trichloroethane, trichloroethylene, and
      tetrachloroethylene, 0.125 microg L(-1) for toluene, and 0.025 microg L(-1) for
      ethylbenzene, m/p-xylene, and o-xylene. In the experiments with T (as) and T
      (fiber) of -20 degrees C, detection limits were reduced for compounds of low
      hydrophobicity (Kow<501), for example benzene, toluene, 1,1,1-trichloroethane,
      and trichloroethylene. In the concentration range 0.5-62.5 microg L(-1), the
      sensitivity of HS-SPME was enhanced by a factor of approximately two for all
      compounds by performing the extraction at -20 degrees C. A possible explanation
      is that freezing of the water sample results in higher concentration of the
      target compounds in the residual liquid phase and gas phase (freezing-out),
      combined with enhanced adsorption of the compounds by the cooled fiber. The
      precision of HS-SPME, expressed as the relative standard deviation and the
      linearity of the regression lines, is increased for more hydrophobic compounds
      (Kow>501) by simultaneous direct fiber cooling and freezing of analyte solution.
      Background contamination during analysis is reduced significantly by avoiding the
      use of organic solvents.

PMID- 16953319
TI  - Determination of cadmium in oyster tissue using isotope dilution inductively
      coupled plasma mass spectrometry: comparison of results obtained in the standard
      and He/H2 cell modes.
AB  - An inductively coupled plasma quadrupole mass spectrometer equipped with an
      octopole collision/reaction cell was used for the determination of cadmium in
      oyster tissue samples using isotope dilution inductively coupled plasma mass
      spectrometry. The oyster samples in question were found to contain Mo and Zr. In
      our feasibility study on a Cd standard solution (10 microg L(-1)) containing a
      matrix of Mo (1000 microg L(-1)) or Zr (250 microg L(-1)), the potentially
      interfering species (MoO(+) or ZrO(+)) present at the analytical mass of cadmium
      concerned (m/z 111, 112 or 114) was reduced effectively through the use of a
      mixture of He and H(2) as cell gases. The accuracy of the method was validated by
      the analysis of a matrix-matched certified reference material (CRM) of NIST SRM
      1566b. The CRM was analyzed under the standard and He/H(2) cell modes. Two
      isotopic pairs of (114)Cd/(111)Cd and (112)Cd/(111)Cd were selected for
      quantification purposes. The recoveries of cadmium obtained in the two cell modes
      were compared with each other. The validated method was applied successfully to
      the APMP.QM-P5 pilot study for international comparability purposes.

PMID- 16953320
TI  - Fluorescent detection of peptides and amino acids for capillary electrophoresis
      via on-line derivatization with 4-fluoro-7-nitro-2,1,3-benzoxadiazole.
AB  - An in-capillary derivatization of amino acids and peptides with 4-fluoro-7-nitro
      2,1,3-benzoxadiazole (NBD-F) was developed for their subsequent capillary
      electrophoretic analysis with laser-induced fluorescence detection (lambda
      (ex)=488 nm). The in-capillary derivatization was achieved in zone-passing mode
      by introducing successive plugs of sample and NBD-F into a fused silica capillary
      previously equilibrated with an alkaline borate buffer. To prevent NBD-F
      hydrolysis and to achieve a reliable derivatization, NBD-F was prepared daily in
      absolute ethanol and a plug of absolute ethanol was introduced between the sample
      and NBD-F reagent plugs. Various parameters influencing the derivatization
      efficiency were investigated and the optimum conditions were as follows:
      background electrolyte (BGE), 20 mM borate buffer (pH 8.8); introduction time, 4
      s for sample and 2 s for NBD-F; molar ratio of NBD-F/sample, above 215;
      temperature, 45 degrees C for amino acids and 35 degrees C for peptides; applied
      voltage, +15 kV. The validation of the in-capillary derivatization method under
      optimal conditions showed a good linearity between the heights of the derivative
      peaks and the concentrations of the amino acids. The intra-day relative standard
      deviations of the migration times and the peak heights were less than 1.3% and
      4.6%, respectively. The efficient derivatization and separation of a mixture of
      valine, alanine, glutamic acid and aspartic acid were achieved using this
      technique. Peptides such as buccaline and beta-protein fragment 1-42 could also
      be derivatized using the developed in-capillary derivatization procedure.

PMID- 16953321
TI  - Human urine certified reference material CZ 6010: creatinine and toluene
      metabolites (hippuric acid and o-cresol) and a benzene metabolite (phenol).
AB  - A reference material for the biological monitoring of occupational exposure to
      toluene, benzene and phenol was prepared. O-cresol and hippuric acid (metabolites
      of toluene) are used for the biological monitoring of occupational exposure to
      toluene. Phenol, a metabolite of benzene, is used for the biological monitoring
      of exposure to benzene, but phenol can of course also be used as an indicator of
      exposure to phenol as well. The reference material (RM) used for the
      determination of these metabolites was prepared by freeze-drying pooled urine
      samples obtained from healthy persons occupationally exposed to toluene and those
      taking part in an inhalation experiment. Tests for homogeneity and stability were
      performed by determining urine concentrations of o-cresol, hippuric acid,
      creatinine and phenol. To investigate the stability of the RM, the urinary
      concentrations of o-cresol and phenol were monitored for eighteen months using GC
      and HPLC, while those of hippuric acid and creatinine were followed for five and
      six years, respectively, using HPLC. Analysis of variance showed that the
      concentrations did not change. The certified concentration values (and their
      uncertainties) of the substances in this reference material (phenol concentration
      c=6.46+/-0.58 mg l(-1); o-cresol concentration c=1.17+/-0.15 mg l(-1); hippuric
      acid concentration c=1328+/-30 mg l(-1); creatinine concentration c=0.82+/-0.10 g
      l(-1)) were evaluated via the interactive statistical programme IPECA.

PMID- 16953322
TI  - New insights into the regulatory mechanisms of the LuxR family of quorum sensing
      regulators.
AB  - Bacteria use small signal molecules, referred to as autoinducers, in order to
      monitor their population density and coordinate gene expression in a process
      named quorum sensing. In Gram-negative bacteria, acylated homoserine lactones are
      the most common autoinducer used for cell-to-cell communication. Increasing
      evidence that many different functions are controlled by acylated homoserine
      lactone quorum sensing has stimulated intensive investigations into the
      physiology, molecular biology and biochemistry that underlie this process. Here
      we review our current understanding of the molecular mechanisms used by the
      transcriptional regulators responsive to acylated homoserine lactone autoinducers
      to control gene expression and the structural modifications induced by acylated
      homoserine lactones binding specifically on these regulators.

PMID- 16953323
TI  - Long-wavelength fluorimetry as an indirect detection system in immunoaffinity
      chromatography: application to environmental analysis.
AB  - The potential of long-wavelength fluorimetry when used as the detection system in
      immunoaffinity chromatography is assessed for the first time by applying this
      approach to the analysis of water and sludge samples. Nile blue (NB) was used to
      synthesize a long-wavelength fluorescent tracer for linear alkylbenzenesulfonates
      (LASs) using the carbodiimide method, in which the amino group of NB is
      covalently coupled to the activated carboxylic acid group of a LAS mimic with N
      hydroxysuccinimide and dicyclohexylcarbodiimide. The method consists of the
      injection of a pre-incubated mixture containing linear sodium 4
      dodecylbenzenesulfonate (LDS; used as the LAS model), anti-LAS antibodies, and
      the long-wavelength tracer into a commercial Protein G column. Free and bound
      tracer fractions are separated in the column, and the peak height of the
      immunochromatogram (corresponding to the free tracer) is directly measured at 626
      nm (lambda (ex)) and 674 nm (lambda (em)), and then correlated to the analyte
      concentration. It is not necessary to perform an elution step immediately after
      every sample application. The dynamic range of the method is 0.05-2.5 microg ml(
      1) LDS, and the detection limit is 15 ng ml(-1). The precision, expressed as the
      relative standard deviation, is 4.8-6.4%. Other surfactants (sodium
      dodecylsulfate and Triton X-100) do not cause interference. The recoveries
      obtained by applying the method to the analysis of water (ground- and wastewater)
      and sludge (primary and activated) samples ranged from 86.0 to 111.3%. Water
      sample analysis included an initial solid-phase extraction step, which cleaned up
      the samples and improved the detection limit fivefold.

PMID- 16953324
TI  - Certified reference materials for inorganic and organic contaminants in
      environmental matrices.
AB  - Chemical measurements often constitute the basis for informed decision-making at
      different levels in society; sound decision-making is possible only if the
      quality of the data used is uncompromised. To guarantee the reliability and
      comparability of analytical data an intricate system of quality-assurance
      measures has to be put into effect in a laboratory. Reference materials and, in
      particular, certified reference materials (CRMs) are essential for achieving
      traceability and comparability of measurement results between laboratories and
      over time. As in any other domain of analytical chemistry, techniques used to
      monitor the levels and fate of contaminants in the environment must be calibrated
      using appropriate calibration materials, and the methods must be properly
      validated using fit-for-purpose matrix-matched CRMs, to ensure confidence in the
      data produced. A sufficiently large number of matrix CRMs are available for
      analysis of most elements, and the group of chemicals known as persistent organic
      pollutants, in environmental compartments and biota. The wide variety of
      analyte/level/matrix/matrix property combinations available from several
      suppliers enables analysts to select CRMs which sufficiently match the properties
      of the samples they analyse routinely. Materials value-assigned for the so-called
      emerging pollutants are scarce at the moment, though an objective of current
      development programmes of CRM suppliers is to overcome this problem.

PMID- 16953325
TI  - HILIC mode separation of polar compounds by monolithic silica capillary columns
      coated with polyacrylamide.
AB  - HILIC mode columns were prepared by an on-column polymerization of acrylamide on
      a monolithic silica capillary column modified with N-(3
      trimethoxysilylpropyl)methacrylamide as the anchor group. The products showed
      HILIC mode retention characteristics with three times greater permeability and
      slightly higher column efficiency compared to a commercially available amide-type
      HILIC column packed with 5-mum particles. The selectivity of the monolithic
      silica-based column was similar to that of the particulate column for each group
      of solutes towards nucleosides, nucleic bases and carbohydrate derivatives,
      although a considerable difference was observed in the selectivity for the solute
      groups. Although the retention of solutes based on the polar functionality was
      much smaller with the monolithic silica columns, which had a smaller phase ratio,
      than with the particle-packed column, the former can achieve better separation
      utilizing the high permeability and higher column efficiencies of a longer
      column.

PMID- 16953326
TI  - [Supracondylar fracture of the femur following arthrodesis at the knee].
AB  - We present a 65 year old patient who complained of pain in the right
      supracondylar femur region after minor trauma. He previously underwent
      arthrodesis of the knee and had had several operative treatments for a septic hip
      endoprosthesis on the same side. The MRI showed a fracture of the supracondylar
      femur, which was successfully treated by partial intra- and extramedullary
      minimal invasive osteosynthesis.

PMID- 16953327
TI  - [Abductor repair failure and nerve damage during hip replacement via the
      transgluteal approach. Why less invasive methods of joint replacement are needed,
      and some approaches to solving the problems].
AB  - BACKGROUND: When used for total hip replacement, the lateral approach is
      associated with two frequently iatrogenic, but virtually insoluble problems:
      limping attributable to abductor insufficiency and pain at the greater
      trochanter. They can result from injury to the inferior branch of the superior
      gluteal nerve and/or failure of the abductor repair. MATERIAL AND METHODS: These
      complications are due to the interruption of a voluminous abductor mass at the
      trochanter, which has to be done to allow undisturbed work on the femoral shaft
      and implantation of a straight femoral component while the leg is in the classic
      figure 4 position. When the lateral approach is used they cannot be avoided
      except by application of a technique that does not require the hip to be forced
      into flexion by the figure 4 position. This is possible with only slight
      detachment of anterior parts of the abductors, as described by Watson-Jones, and
      preparation of the femoral shaft as reported by Rottinger, with the hip in
      extension. RESULTS: In comparison with the Rottinger technique, in which the
      surgeon manages without detaching the abductors, the technique with the slight
      detachment lessens the traction on the abductors and lowers the risk of nerve
      damage in the interval between abductor and tensor. CONCLUSION: Whichever
      technique is ultimately selected, it is of decisive importance that in the case
      of an approach to the hip joint by way of an anterior capsulotomy with the
      abductors shifted in the posterior direction, the femoral shaft is prepared with
      the hip in extension.

PMID- 16953328
TI  - [Are computer assisted total knee replacements more accurately placed? A meta
      analysis of comparative studies].
AB  - Computer-assisted surgery (CAS) has become established in many hospitals
      throughout the world, especially in the form of computer navigation for total
      knee replacement (TKR). Analysis of the studies available revealed 18 comparative
      studies examining the precision of implantation of knee endoprostheses following
      CAS and after implantation by the conventional technique. In a meta-analysis of
      13 studies in which the same safe zone of +/-3 from neutral alignment was defined
      for the leg axis, a total of 1,784 TKR were performed. In the group of patients
      in whom the conventional technique was used, 75.6% (654/865) of TKR were
      implanted within the safe zone. In the CAS group 93.9% (863/919) of the
      prostheses were implanted within the safe zone (p<0.0001). The differences
      between the groups were statistically significant in 11 of the 13 studies, and
      the difference between groups for the entire patient population is highly
      significant. Only limited clinical results were ascertained in these comparative
      studies; there were no great differences between the treatment groups in clinical
      course.

PMID- 16953329
TI  - The hard cell(s) of avian transgenesis.
AB  - After 25 years, the search for the avian cell that can be cultured indefinitely,
      genetically modified, and clonally derived while retaining its ability to enter
      the germline has ended. van de Lavoir et al. [2006a, Nature 441:766-769] have
      defined the conditions for culture and genetic modification of primordial germ
      cells (PGCs) and shown that these cells are transmitted at high rates through the
      germline. The advent of this technology provides the ability to introduce
      transgenes of any size and to make site-specific changes to the genome. Although
      PGCs are committed to the germline, they can be induced into somatically
      committed embryonic germ (EG) cells by changing the culture conditions. EG cells
      resemble embryonic stem (ES) cells that are also committed to the somatic
      lineages (van de Lavoir 2006b, Mech Dev 123:31-41). These cell-based systems
      facilitate insertion of larger transgenes that provide high level,
      developmentally regulated and tissue-specific expression in transgenic chimeras
      and their offspring. Following introduction of a transgene, high-grade somatic
      chimeras can be made with ES and EG cells within 4 weeks and 4 months
      respectively, allowing quick assessment of the transgenic phenotype. Following
      introduction of a tansgene into PGCs, high-grade germline chimeras can be made
      within 8-9 weeks and the high rate of germline transmission of G0 chimeras
      produces a large cohort of transgenic chicks in 16-17 weeks. PGC, EG and ES cells
      can be grown in conventional laboratory settings and small flocks of recipient
      birds or third-party vendors can supply recipient embryos to make somatic and/or
      germline chimeras. In general, animal management is routine although some
      specialized equipment and technical skill is required to incubate chimeras in
      surrogate shells.

PMID- 16953330
TI  - Decreased frequency and proliferative response of invariant Valpha24Vbeta11
      natural killer T (iNKT) cells in healthy elderly.
AB  - Invariant natural killer T (iNKT) cells represent a well-established T cell
      lineage characterised in humans by TCR consisting of an invariant alpha chain
      encoded by Valpha24-JalphaQ genes, paired preferentially with a Vbeta11 chain.
      iNKT cells also share some characteristics with NK cells, such as the expression
      of the NK-associated receptor CD161 in humans. The T cell immune response is the
      most dramatically affected by ageing, although age-associated alterations in the
      phenotype and function of other cells of the immune system have been
      demonstrated. Despite the importance of iNKT cells in the regulation of the
      immune response, there are a limited number of studies on the effect of ageing on
      peripheral blood iNKT cells. Thus, in this work we analyse the effect of ageing
      on peripheral blood Valpha24(+)Vbeta11(+) iNKT cells by studying their frequency,
      phenotype and proliferative function in elderly individuals fulfilling the
      SENIEUR criteria of healthy ageing compared with healthy young donors. Our
      results demonstrated a significant decrease of the percentage of
      Valpha24(+)Vbeta11(+) iNKT cells in elderly donors. No significant differences
      were found in the expression of CD27, CD28, CD45RO, CD45RA(bright), CD161, CD94
      and NKG2D on iNKT cells from young and elderly individuals. Proliferation of
      Valpha24(+)Vbeta11(+) iNKT cells in response to alpha-GalCer and IL2 was analysed
      by calculating the cumulative population doubling (PD) after 14 days of culture.
      The PD levels were lower in the elderly indicating that Valpha24(+)Vbeta11(+)
      iNKT cells from healthy elderly subjects had an impaired proliferative capacity.
      These results indicate that ageing associates with a significant decline in the
      percentage and proliferative response of peripheral blood iNKT cells. Given the
      important immunoregulatory role of iNKT cells, these alterations in their number
      and function could contribute to the deleterious immune response in the elderly.

PMID- 16953331
TI  - Correlation between zinc status and immune function in the elderly.
AB  - Zinc is essential for the immune system and elderly people have an increased
      probability for zinc deficiency, documented by a decline of serum or plasma zinc
      levels with age. Although most healthy elderly are not classified as clinically
      zinc deficient, even marginal zinc deprivation can affect immune function.
      Several striking similarities in the immunological changes during aging and zinc
      deficiency, including a reduction in the activity of the thymus and thymic
      hormones, a shift of the T helper cell balance towards TH2, decreased response to
      vaccination, and impaired functions of innae immune cells indicate that a wide
      prevalence of marginal zinc deficiency in elderly people may contribute to
      immunosenescence. Studies with oral zinc supplementation show the potential to
      improve the immune response of elderly people by restoration of the zinc levels,
      showing that balancing the zinc status may be a way to healthy aging. This review
      summarizes the current literature about zinc supplementation in the elderly and
      thereby defines the rationale for the immunological part of the ZINCAGE project.

PMID- 16953332
TI  - Involvement of -308 TNF-alpha and 1267 Hsp70-2 polymorphisms and zinc status in
      the susceptibility of coronary artery disease (CAD) in old patients.
AB  - Coronary artery disease (CAD) is characterized by an inflammatory status and it
      represents the major cause of death in elderly. Zinc deficiency and inflammatory
      genes within major histocompatibility complex (MHC) region are implicated in
      ischaemic heart diseases. TNF-alpha is present in coronary artery plaques and may
      provoke plaque instability. Hsp70 plays instead a pro-atherogenic role, via
      proinflammatory cytokine production, in atherosclerotic lesions contributing to
      plaque rupture. Contradictory data report the association between -308 TNF-alpha
      polymorphism and CAD, while no investigations exist on Hsp70-2 gene in CAD. In
      the current study, we analysed -308 TNF-alpha and 1267 Hsp70-2 polymorphisms and
      zinc status in 190 healthy old controls and 216 old patients with carotid
      stenosis subdivided in two groups: the first one 105 patients with CAD (C group),
      and the second one 111 patients without cardiovascular events (D group). We found
      a lack of association between -308 TNF-alpha polymorphism and CAD. Conversely,
      1267 Hsp70-2 polymorphism was associated with CAD. In particular, significant
      higher frequency of AB + BB genotypes (B + genotype) was observed in C patients
      than controls (71.4 vs.56.9%, P = 0.017, odds ratio = 1.898). However, when C
      patients were subdivided into four subgroups on the basis of presence/absence of
      1267B Hsp70-2 and -308A TNF-alpha alleles, B + A + patients showed higher
      prothrombin activity as well as Hsp70-2, TNF-alpha, IL-6 gene expressions in
      carotid atheroma when compared to B - A - genotypes. The zinc status (plasma and
      Zn/Fe ratio in erythrocytes) is not affected by these polymorphisms. However,
      zinc deficiency is present in CAD condition. In conclusion, 1267 HSP70-2
      polymorphism and zinc deficiency, rather than -308 TNF-alpha, are independently
      associated with CAD. B + A+ and B + A- carriers seem more predisposed to
      ischaemic events; conversely, B - A- genotype may be considered a protective
      marker against CAD.

PMID- 16953333
TI  - Health status, blood and anthropometrical indices from Greek old and nonagenarian
      subjects.
AB  - As the elderly population is increasing rapidly, there is a lot of scientific
      interest in clarifying the differential life-style, genetic, biochemical and
      molecular factors contributing to mortality or exceptional longevity. Within the
      framework of the ZINCAGE project, 249 old (60-85 years) and nonagenarian Greek
      subjects (>/=85 years old) were recruited and anthropometrical, blood and
      biochemical indices as well as blood pressure measurements were obtained. Based
      upon the inclusion criteria, 214 of them were characterized as healthy (136
      female, 78 male), while those characterized as non-healthy were excluded from the
      statistical analysis. The findings indicated an 88.4% prevalence of overweight
      and obesity in elderly (91.2% in women, 83.3% in men), while a significant
      decrease in body mass index with age was recorded. Hypercholesterolemia was
      observed in 75.3% of elderly women and in 69.2% of men. Erythrocyte sedimentation
      rate value was increased in 27.6% of all healthy elderly, while zinc deficiency
      was observed in 18.7% of elderly. Over 85.0% of all healthy elderly were within
      normal range for all other hematological analysis. Blood analysis confirmed the
      good health status of the elderly recruited as healthy, except for the high
      prevalence of obesity and hypercholesterolemia.

PMID- 16953334
TI  - Zinc and ageing (ZINCAGE Project).

PMID- 16953335
TI  - Reduction in the in vitro expression of Brain-Pancreas Relative Protein by oxygen
      and glucose-deprivation.
AB  - Brain-Pancreas Relative Protein (BPRP) is a novel protein found in our
      laboratory. In previous study we observed a significant reduction in BPRP in
      ischemic brain of rat. Here we undertook this study to explore the possible
      mediating mechanism by which oxygen and glucose-deprivation culture (OGD), a
      model of ischemia in vitro, decreased the expression of BPRP in PC12 cells. BPRP
      was found to be expressed in PC12 cells and OGD caused a significant reduction in
      BPRP expression. The effect of OGD was primarily mediated by reactive oxygen
      species (ROS) because OGD upregulated the production of ROS and the inhibitors of
      protein kinase C, calmodulin, free radical scavengers reduced OGD-induced ROS
      production, while increased the expression of BPRP in PC12 cells. These data
      indicate that OGD decreases the expression of BPRP via enhanced formation of
      intracellular ROS.

PMID- 16953336
TI  - Restorative effect of Kalpaamruthaa, an indigenous preparation, on oxidative
      damage in mammary gland mitochondrial fraction in experimental mammary carcinoma.
AB  - Cancer prevention and treatment using phytochemicals have attracted increased
      interest. Recent studies have shown that Semecarpus anacardium Linn nut milk
      extract (SA), a promising antioxidant and anticancer drug, exerts its anticancer
      effect through reducing or quenching reactive oxygen species under different
      conditions. The present study examined whether Phyllanthus emblica Linn fruit,
      rich in vitamin C content synergistically in combination can enhance both the
      antioxidant and anticancer activity of S. anacardium nut milk extract in 7, 12
      dimethyl benz[a]anthracene (DMBA)-induced experimental mammary carcinoma in rat
      model. Female Sprague Dawley rats of 180 +/- 10 g were categorized into six
      groups. Three groups were administered DMBA (25mg/rat, orally) dissolved in olive
      oil to induce mammary carcinoma. One of these groups received Kalpaamruthaa (KA)
      (300 mg/kg b.wt, orally) and other group received SA (200mg/kg b.wt, orally) for
      14 days after 90 days of DMBA induction. A vehicle treated control and drug
      control groups were also included. The mitochondrial fraction of untreated DMBA
      induced mammary gland showed 2.61-fold increase in lipid peroxidation level and
      abnormal changes in the activities/levels of mitochondrial enzymic (superoxide
      dismutase, glutathione peroxidase and glutathione reductase) and non-enzymic
      (glutathione, vitamin C and vitamin E) antioxidants were observed. DMBA treated
      rats also showed decline in the activities of mitochondrial enzymes such as
      succinate dehydrogenase, malate dehydrogenase, alpha-ketoglutarate dehydrogenase
      and isocitrate dehydrogenase. In contrast, rats treated with Kalpaamruthaa showed
      normal lipid peroxide level and antioxidant defenses. The results of the present
      study highlight the improved antioxidant property of KA than sole treatment of S.
      anacardium nut milk extract.

PMID- 16953337
TI  - Increased PC-1 phosphodiesterase activity and inhibition of glucose uptake in
      adipocytes of type 2 diabetic rats.
AB  - This study was designed to understand the cellular mechanisms responsible for
      defects in the insulin-stimulated signal transduction pathway in a type 2
      diabetic animal model. We examined the in vitro PC-1 phosphodiesterase activity
      and glucose uptake in adipose tissue of streptozotocin (STZ)-induced type 2
      diabetic rats. The PC-1 activity was significantly increased in adipose tissue of
      diabetic rats (0.54 +/- 0.08 nmol PNTP hydrolyzed/mg protein/min) compared with
      controls (0.29 +/- 0.05 nmol PNTP hydrolyzed/mg protein/min, p < 0.05). Upon
      insulin stimulation (100 nM), glucose uptake in the adipose tissue of the
      controls (4.17 +/- 1.28 x 10(-8) micromol/mg/min) was significantly higher than
      that in the diabetic rats (1.26 +/- 0.35 x 10(-8); p < 0.05). These results
      suggest that elevated PC-1 phosphodiesterase activity and decreased glucose
      uptake in adipose tissues may be acquired characteristics contributing to the
      development of type 2 diabetes mellitus.

PMID- 16953338
TI  - Bilateral congenital anterior diaphragmatic hernia: a case report.
AB  - The anteromedial diaphragmatic hernias of Morgagni and Larrey are the least
      common defects that occur in this organ. Simultaneous occurrence has been
      described but remains an absolute rarity. We herein present a case of this
      bilateral herniation with a unique presentation. The paper refers to the basic
      anatomic, diagnostic and therapeutic considerations for this entity.

PMID- 16953339
TI  - Bio-image warehouse system: concept and implementation of a diagnosis-based data
      warehouse for advanced imaging modalities in neuroradiology.
AB  - Advanced neuroimaging techniques, such as functional magnetic resonance imaging
      (fMRI), chemical shift spectroscopy imaging (CSI), diffusion tensor imaging
      (DTI), and perfusion-weighted imaging (PWI) create novel challenges in terms of
      data storage and management: huge amounts of raw data are generated, the results
      of analysis may depend on the software and settings that have been used, and most
      often intermediate files are inherently not compliant with the current DICOM
      (digital imaging and communication in medicine) standard, as they contain
      multidimensional complex and tensor arrays and various other types of data
      structures. A software architecture, referred to as Bio-Image Warehouse System
      (BIWS), which can be used alongside a radiology information system/picture
      archiving and communication system (RIS/PACS) system to store neuroimaging data
      for research purposes, is presented. The system architecture is conceived with
      the purpose of enabling to query by diagnosis according to a predefined two
      layered classification taxonomy. The operational impact of the system and the
      time needed to get acquainted with the web-based interface and with the taxonomy
      are found to be limited. The development of modules enabling automated creation
      of statistical templates is proposed.

PMID- 16953340
TI  - Analog to digital workflow improvement: a quantitative study.
AB  - This study tracked a radiology department's conversion from utilization of a
      Kodak Amber analog system to a Kodak DirectView DR 5100 digital system. Through
      the use of ProModel Optimization Suite, a workflow simulation software package,
      significant quantitative information was derived from workflow process data
      measured before and after the change to a digital system. Once the digital room
      was fully operational and the radiology staff comfortable with the new system,
      average patient examination time was reduced from 9.24 to 5.28 min, indicating
      that a higher patient throughput could be achieved. Compared to the analog
      system, chest examination time for modality specific activities was reduced by
      43%. The percentage of repeat examinations experienced with the digital system
      also decreased to 8% vs. the level of 9.5% experienced with the analog system.
      The study indicated that it is possible to quantitatively study clinical workflow
      and productivity by using commercially available software.

PMID- 16953341
TI  - A non-Gaussian model in polymeric network.
AB  - We investigate a finite chain approximation, the non-Gaussian Tsallis
      distribution, to the polymeric network, which gives an improvement to the
      Gaussian model. This distribution presents some necessary characteristics, like a
      cutoff to the maximum chain length and a continuous limit to the Gaussian one for
      a large number of monomers. It also presents a simple quadratic structure that
      allows to generalize the Gaussian properties such as exact-moments calculation
      and Wick theorem. We obtain the free-energy density in its full tensorial
      structure.

PMID- 16953342
TI  - Dynamics and mechanics of motor-filament systems.
AB  - Motivated by the cytoskeleton of eukaryotic cells, we develop a general framework
      for describing the large-scale dynamics of an active filament network. In the
      cytoskeleton, active cross-links are formed by motor proteins that are able to
      induce relative motion between filaments. Starting from pair-wise interactions of
      filaments via such active processes, our framework is based on momentum
      conservation and an analysis of the momentum flux. This allows us to calculate
      the stresses in the filament network generated by the action of motor proteins.
      We derive effective theories for the filament dynamics which can be related to
      continuum theories of active polar gels. As an example, we discuss the stability
      of homogenous isotropic filament distributions in two spatial dimensions.

PMID- 16953343
TI  - Temperature dependence of the effective anchoring energy for a nematic
      ferroelectric interface.
AB  - Specific features of the anisotropic interaction between a nematic mixture and a
      polar surface of a ferroelectric triglycine sulfate crystal have been studied
      over a wide temperature range including the substrate's Curie point T(c). The
      mixture was composed of two nematic liquid crystals, 60% of p-methoxybenzylidene
      p-n-butylaniline (MBBA) and 40% of p-ethoxybenzylidene-p-n-butylaniline (EBBA),
      and doped with a small amount of a dichroic dye. The temperature dependence of
      the polarized components of optical density D(j) of the dye absorption band for
      the nematic and isotropic phases of the MBBA+EBBA mixture has been obtained using
      polarization optic techniques. The temperature-induced structural changes in the
      nematic layer near T(c) were found to be related to the changes in the
      orientational part of the tensor order parameter Q(ik). The experimental data
      have been interpreted using the model, in which the dispersive van der Waals
      forces of the substrate stabilize the planar orientation of the nematic in the
      bulk competing with the short-range anchoring forces in the vicinity of T(c). At
      the same time, the anisotropic part of the surface energy has two terms with the
      orthogonal easy axes. The nature of the surface electric field and its effect on
      the director alignment at the interface have been clarified. Taking into account
      the known relation between anchoring strength and the nematic order parameter,
      the effective anchoring energy w(eff) for the studied system has been determined
      as a function of temperature.

PMID- 16953344
TI  - Self-assembled pattern formation of block copolymers on the surface of the sphere
      using self-consistent field theory.
AB  - The spherical surface is spatially discretized with triangular lattices to
      numerically calculate the Laplace-Beltrami operator contained in the self
      consistent field theory (SCFT) equations using a finite volume method. Based on
      this method we have developed a spherical alternating-direction implicit (ADI)
      scheme for the first time to help extend real-space implementation of SCFT in 2D
      flat space to the surface of the sphere. By using this method, we simulate the
      equilibrium microphase separation morphology of block copolymers including AB
      diblocks, ABC linear triblocks and ABC star triblock copolymers occurred on the
      spherical surface. In general, two classes of microphase separation morphologies
      such as striped patterns for compositionally symmetric block copolymers and
      spotted patterns for asymmetric compositions have been found. In contrast to
      microphase separation morphology in 2D flat space, the geometrical
      characteristics of a sphere has a large influence on the self-assembled
      morphology. For striped patterns, several of spiral-form and ring-form patterns
      are found by changing the ratio of the radius of a sphere to the averaging width
      of the stripes. The specific pattern such as the striped and spotted pattern with
      intrinsic dislocations or defects stems from formed periodic patterns due to
      microphase separation of block copolymers arranged on the curved surface.

PMID- 16953345
TI  - Laser manipulation of a smectic liquid-crystal droplet.
AB  - The laser trapping of a smectic-A liquid-crystal micro-droplet was spatially
      traced during its transient into the trapped position. The lateral and angular
      orientation of the droplet were determined and followed in time during the axial
      descent of the micro-droplet into the stationary trapped position using the
      analysis of polarization changes of the light passed through the droplet with
      temporal resolution of a video refresh rate of 30 ms. The spatial resolution of
      0.1-1 microm has been achieved for typical laser trapping powers of 2-600 mW. The
      axial profile of a laser trapping force (an ellipticity of the focal spot) has
      been determined. The laser trapping mechanism of smectic micro-droplets is
      discussed in terms of minimization of a light-droplet interaction.

PMID- 16953346
TI  - Intramedullary locking compression nail for the treatment of an olecranon
      fracture.
AB  - OBJECTIVE: Reconstruction of the anatomy of the olecranon, while protecting the
      soft tissue, by an internal stabilization method that is stable under exertion.
      INDICATIONS: All olecranon fractures. CONTRAINDICATIONS: Very small (< 5 mm)
      proximal fragments at the point of nail entry. Bony avulsions of the triceps
      tendon. SURGICAL TECHNIQUE: In the case of displaced olecranon fractures,
      exposure of the ulnar nerve, open reduction, fracture retention with reduction
      forceps, introduction of a 1.6 or 2.0 mm thick central guide wire into the
      medullary cavity in a slightly radial direction, overdrilling with a 3.5- or 4.5
      mm cannulated drill bit, introduction of the nail to the aiming arm, and locking
      with 2.0-mm threaded wires. If the fracture pattern is transverse or slightly
      oblique, axial compression can be achieved by insertion of a compression screw
      into the nail. Fragments from the posterior margin or medial/lateral comminuted
      zones can be fixed more securely to the system via fiber cerclage wires around
      the threaded wires. After checking by X-ray, shortening of the threaded wires
      with the bolt cutters. POSTOPERATIVE MANAGEMENT: Stable under exertion, splint
      free postoperative management for 6 weeks, followed by full load bearing.
      RESULTS: From May 1999 to December 2002, 80 olecranon fractures were treated
      using the XS nail. 73 patients (91.3%) were followed up after an average of 15
      months. 49 (67.1%) had a multifragmentary or comminuted fracture, and 24 (32.9%)
      a simple transverse fracture. According to the Murphy Score, results were
      excellent in 47 cases (64.4%), good in 21 (28.8%), satisfactory in three (4.1%),
      and poor in two (2.7%).

PMID- 16953347
TI  - Improved implantation technique for resurfacing arthroplasty of the hip.
AB  - OBJECTIVE: Prevention of incorrect positioning of the surface replacement,
      whereby the center of the femoral head for the implantation of the replacement
      surface is ascertained by central drilling of the femoral neck under image
      intensifier control. INDICATIONS: An arthritically damaged, but not too severely
      deformed femoral head that can be reamed without injuring the femoral neck.
      CONTRAINDICATIONS: Hip ankylosis. Femoral head necrosis. Severe deformity of the
      femoral head. State after varus osteotomy. SURGICAL TECHNIQUE: Using a 6-mm drill
      bit, the femoral neck of the affected hip is drilled from lateral to medial under
      anteroposterior and lateral imaging deliberately perforating the femoral head.
      The hip joint is exposed through a minimized invasive anterolateral, lateral, or
      posterior approach and dislocated. A guide rod corresponding in size to the 6-mm
      drill channel is inserted into the drill hole; it serves as a guide for all
      subsequent preparations of the femoral head, depending on the type of prosthesis.
      After implantation of the corresponding acetabular component, resurfacing of the
      femoral head is done. Reduction of the joint completes surgery. RESULTS: In the
      first 14 hips the midpoint of the femoral head was ascertained by using the
      manufacturer's centering device. In 31 subsequent hips the midpoint of the
      femoral head was found by central drilling of the femoral neck. Using the
      centering device, the average deviation of the angle of the prosthesis from the
      preoperative CCD angle was 7 degrees (+/- 5.7 degrees ); for central drilling of
      the femoral neck it was only 3 degrees (+/- 3.4 degrees ). The exact alignment of
      the resurfacing component is crucial for the success of surgery. It is achieved
      with greater precision with central drilling of the neck than with the
      manufacturer's centering device.

PMID- 16953348
TI  - Percutaneous iliosacral screw fixation of unstable pelvic injuries by
      conventional fluoroscopy.
AB  - OBJECTIVE: Closed reduction and retention of translatory unstable pelvic injuries
      (type C injuries), in order to restore the form and function of the posterior
      pelvis by percutaneous iliosacral screw osteosynthesis, using conventional
      fluoroscopy. INDICATIONS: Definitive treatment of the posterior pelvis in type C
      injuries (AO classification) with complete sacral fracture, sacroiliac joint (SI
      joint) dislocation, transiliac or transsacral dislocation fracture of the SI
      joint with insignificant small fragment and sacroiliac avulsion injuries which
      can be reduced almost anatomically in closed technique. CONTRAINDICATIONS: Poor
      general health, local soft-tissue damage, rotationally unstable type B pelvic
      injuries as well as type C injuries which cannot be reduced satisfactorily in
      closed technique. SURGICAL TECHNIQUE: Closed reduction, stab incision and
      percutaneous stabilization of the posterior pelvis by transiliosacral screw
      osteosynthesis, guided by fluoroscopy. POSTOPERATIVE MANAGEMENT: Partial loading
      of the injured side with 15 kg for 8-12 weeks with two underarm crutches. Implant
      removal 6-12 months after injury. RESULTS: 20 patients with a transforaminal
      sacral fracture consistent with a type C pelvic injury underwent screw fixation
      with fluoroscopy with 7.3-mm cannulated screws, placed in a transiliosacral
      position in the vertebral body of S1. The average preoperative displacement of
      3.8 mm was decreased by closed reduction to 1.6 mm postoperatively. The average
      operating time was 55 min, the average screening time 2.22 min. Incorrect screw
      position with no consequences was observed in three patients; iatrogenic nerve
      damage was not found. All fractures healed within 3 months.

PMID- 16953349
TI  - The use of fresh allografts in osteochondrosis dissecans of the lateral femoral
      condyle.
AB  - OBJECTIVE: Reconstruction of joint surface by using allografts to fill extensive
      bone-cartilage defects. INDICATIONS: Bone-cartilage defects ranging from a
      diagonal length of at least 3 cm and a depth of minimum 1 cm to maximum the
      entire lateral femoral condyle, e. g., following trauma, in the case of
      osteochondrosis dissecans, or following the resection of benign tumors.
      CONTRAINDICATIONS: Arthrosis. Minor or superficial cartilage defects. Bipolar
      defects. SURGICAL TECHNIQUE: The transplant bed is reamed precisely into the
      recipient's knee, the donor knee is opened, the block required for
      transplantation is measured, prepared and press-fit inserted. A straight leg axis
      is required for a good surgical result. POSTOPERATIVE MANAGEMENT: No weight
      bearing on the operated leg, two underarm crutches for 10 weeks, then partial
      weight bearing and further increase in weight bearing depending on postoperative
      allograft healing. CT follow-ups to assess postoperative healing of the
      transplant after 3 and after 8-12 months. Sporting activities that put pressure
      on the knee joint should not be undertaken until at least 1 year after surgery;
      cycling and swimming-depending on the CT-from the 6th postoperative month onward.
      RESULTS: Three male patients aged 21 (n = 2) and 28 (n = 1) were operated on for
      osteochondrosis dissecans of the lateral femoral condyle and observed for an
      average of 26 months. Postoperative healing of the transplanted tissue was
      confirmed in all patients by means of CT. For two of them, the vitality of the
      transplant was confirmed by means of MRT and contrast agents, and good
      postoperative healing of the transplant was also represented arthroscopically.
      All patients were subjectively satisfied, without complaints, and had improved
      range of motion in the operated knee.

PMID- 16953350
TI  - Planning analysis of knee-adjacent deformities. I. Frontal plane deformities.
AB  - The planning analysis of leg deformities around the knee joint is based on a
      standardized clinical examination and on long leg standing anteroposterior (AP)
      radiographs, which may be complemented by spot-film radiographs and stress
      radiographs. The principles of true-nominal analysis in six steps are used to
      characterize the deformity and plan the corrective osteotomy: 1. Drawing in the
      anatomic points of reference. 2. Establishing the mechanical weight-bearing axis.
      3. Determining the axis and orientation angles around the knee joint. 4.
      Determining the correction goal. 5. Deciding on the osteosynthesis technique and
      the osteotomy level. 6. Measuring the angle of correction. All the steps are
      exemplified on a valgus deformity and a varus deformity.

PMID- 16953351
TI  - Open-wedge osteotomy of the lateral femoral condyle for extensor mechanism
      instability.
AB  - OBJECTIVE: To achieve extensor mechanism stability in postpatellectomy patients
      by elevating the lateral femoral condyle, thus creating a deeper trochlear
      groove. INDICATIONS: Instability of the quadriceps tendon after patellectomy and
      other realignment interventions, including but not limited to the release of the
      lateral patellofemoral ligaments, advancement of the vastus medialis obliquus
      muscle and, in some cases, transfer of the tibial tubercle. Stabilization of a
      normal dislocating patella in presence of a hypoplastic lateral femoral condyle.
      CONTRAINDICATIONS: Medical conditions precluding surgery. SURGICAL TECHNIQUE: An
      open-wedge osteotomy of the lateral femoral condyle is performed. Predrilling at
      the osteotomy level is followed by a multiple-step curved-type osteotomy starting
      laterally, directed upward to the trochlea. Bone wedges are inserted under the
      levered bony fragment and the intrinsically stable osteotomy is secured with one
      or more countersunk screws. POSTOPERATIVE MANAGEMENT: A removable splint is
      applied in 30 degrees of knee flexion. With patellectomy, the splint is applied
      in 90 degrees of knee flexion for the first 3 days. Continuous passive motion and
      partial weight bearing are started 4 days after surgery in all patients. Use of
      the splint is advocated for 6 weeks in total. RESULTS: Eight knees (six patients)
      with extensor mechanism instability underwent this procedure. In five knees
      patellectomy had been performed earlier, one patient underwent an osteotomy
      combined with patellectomy bilaterally, in one patient a normal patella was left
      in situ. No instability was reported after surgery (average follow-up 8 years,
      range 2-17 years). Modified Lysholm Knee Scores showed two excellent, two good,
      and four fair results. Follow-up radiographs showed a healed osteotomy and an
      increase in trochlear depth.

PMID- 16953352
TI  - Effective disinfection of orthodontic pliers.
AB  - OBJECTIVE: Pathogenic microbes may be transmitted directly from the orthodontist
      to the patient or from the patient to the doctor, and indirectly from patient to
      patient. The latter may occur via contaminated instruments or surfaces, and is
      referred to as cross-contamination. The objective of this study was to evaluate
      the extent of bacterial contamination of orthodontic pliers and the efficacy of
      the disinfection techniques applied after clinical use. We also sought to examine
      under standardized conditions the virucidal, bactericidal and fungicidal effects
      of disinfection techniques used in practice. MATERIALS AND METHODS: The efficacy
      of various disinfection methods was determined after clinical use in-vivo on 10
      test subjects and in-vitro with deliberate contamination. The following
      disinfection methods were tested: 1. Iso-Septol spray 2. Incidur spray 3. Trough
      disinfection in combination with 5% Sekusept Plus solution 4. Ultrasound bath in
      combination with 5% Sekusept Plus solution 5. Thermal disinfection For in-vitro
      contamination we used the test organisms Staphylococcus aureus, Escherichia coli,
      Candida albicans, Coxsackie virus B4, HSV 1, and Adenovirus type 5. The tests
      were carried out six to eight times for each organism. The Weingart pliers and
      distalend cutters were tested. The criteria for effective disinfection were a
      reduction in infectiosity of five log steps (for bacteria and fungi) or four log
      steps (viruses). Statistical analysis was carried out using the Wilcoxon and
      Whitney U-test. RESULTS: The presence of contamination following clinical use was
      not adequately eliminated with all disinfection methods. The spray methods
      exhibited shortcomings in disinfection. For the type of contamination defined,
      trough disinfection with 5% Sekusept Plus and the Incidur and Iso-Septol spray
      disinfection methods provided insufficient disinfection. Conversely, the
      ultrasound bath with 5% Sekusept Plus solution and steam disinfection met the
      criteria for effective disinfection for all microbes. No statistically
      significant difference was found between the oiled and unoiled states. In some
      cases, there were slightly higher rates of contamination with the Weingart pliers
      as with the distalend cutters. However, these were not statistically significant.
      CONCLUSIONS: It should be possible to disinfect lipophilic viruses and the usual
      bacterial infections adequately with all methods, provided that the use of sprays
      and trough disinfection is preceded by cleaning with brush and water, followed by
      drying. With hydrophilic viruses, however, the spray and trough disinfection
      methods are limited in their efficacy and cannot be considered adequate.
      Exclusively chemical methods are therefore less effective than thermal or
      physical-chemical methods. Thermal disinfection and the ultrasound bath in
      combination with 5% Sekusept Plus are clearly superior to spray disinfection and
      trough disinfection alone. The ultrasound bath and thermal disinfection can
      therefore be recommended for the disinfection of orthodontic pliers. We recommend
      that the pliers be cleaned beforehand due to their uneven surfaces.

PMID- 16953353
TI  - Dental care during orthodontic treatment with electric toothbrushes.
AB  - OBJECTIVE: In an in-vitro experimental set-up, we tested the efficacy of
      different electric toothbrushes in cleaning teeth with a multibracket appliance.
      MATERIAL AND METHODS: The efficacy of three sonic and four rotating toothbrushes
      were compared; the brushes removed artificial plaque from plastic teeth. The
      amount of removed plaque substitute was determined via a comparative photo
      analysis with one picture of the teeth before and one picture after the brushing
      cycle. Two views of the tooth segment were chosen: one vestibular view and one
      apical view of the areas behind the bracket wings. All tests were carried out
      with water, elmex and Pearls and Dents as brushing media. RESULTS: The data
      showed greater brushing efficacy when Pearls and Dents toothpaste was used. The
      Sonicare toothbrush was the most efficient. The Sonicmax and rotating Oral-B
      ProfessionalCare 7000 were also very efficacious. On average, all the other
      toothbrushes performed less well. All toothbrushes were capable of brushing the
      undercut areas behind the bracket wings, with plaque removal being the greatest
      when the Sonicare toothbrush was used together with Pearls and Dents.
      CONCLUSIONS: The best electric toothbrushes did not demonstrate good tooth
      cleaning. Longer brushing times, mastery of the proper brushing technique, and/or
      special toothbrush heads are absolutely necessary.

PMID- 16953354
TI  - Dental findings in patients with ectodermal dysplasia.
AB  - BACKGROUND: Ectodermal dysplasia is an inherited disease causing malformations of
      all tissues originating from the ectoderm. The significance of this disease lies
      in severe hypodontia, and an accompanying hypoplasia of the alveolar process. The
      clinical situation is aggravated by a significant xerostomia. It was the aim of
      this study to document the distribution of hypodontia and tooth malformation.
      Furthermore, we aimed to elucidate the clinical impact of these findings.
      PATIENTS AND METHODS: Records of 30 patients (19 males, 11 females) suffering
      from ectodermal dysplasia were included. Their age ranged between 7 and 23 years.
      All patients had been examined clinically and radiographically. In every patient,
      a record was made of which teeth were missing or malformed, and which deciduous
      teeth persisted. Additionally, the entire treatment procedure was assessed.
      RESULTS: The third molars were missing in all of the patients. The number of
      aplastic permanent teeth ranged from 2 to 26. The maxillary lateral incisors were
      most frequently absent, followed by the mandibular central incisors. The most
      stable teeth were the central incisors of the upper jaw, and the canines and
      first molars in both jaws. However, the maxillary central incisors and canines
      were the teeth most affected by malformation. Deciduous canines and second molars
      were the most often persisting teeth due to agenesis of the maxillary lateral
      permanent incisors and mandibular second premolars. In two-thirds of the
      patients, missing teeth were replaced by removable dentures. Half of the patients
      received orthodontic treatment. CONCLUSIONS: Hypodontia and malformation are
      almost regular dental characteristics in patients suffering from ectodermal
      dysplasia. The distribution of absent teeth deviates remarkably from the general
      population. Treatment requires an interdisciplinary approach including
      orthodontics, prosthodontics and oral surgery.

PMID- 16953355
TI  - Disc-condyle Relationships during Class II Treatment with the Functional
      Mandibular Advancer (FMA).
AB  - OBJECTIVE: The objective of this study was to verify the effects of treatment to
      correct Class II malocclusion with the Functional Mandibular Advancer (FMA) on
      the relative positions of the articular disc and mandibular condyle. In
      particular, we aimed to find out whether the disc-condyle relationship changed
      between baseline and post-treatment, in temporomandibular joints initially
      exhibiting a physiological relationship and alternatively, in temporomandibular
      joints initially presenting anterior displacement of the articular disc. PATIENTS
      AND METHODS: Treatment progress in 15 patients was monitored at defined points in
      time by manual structural analysis (MSA) and magnetic resonance (MR) imaging. The
      disc-condyle relationship was assessed by examining the parasagittal MR images
      made up of three slices each (lateral, central, medial) taken in habitual
      intercuspation and maximum-open mouth position. The MR images were metrically
      analyzed to determine the sagittal positional relationship of the articular disc
      and mandibular condyle using two methods on the central slices of the images
      taken in closed-mouth position. MSA was used in particular to determine the disc
      condyle relationships and to metrically record the extent of active movement of
      the mandible during mouth opening, protrusion, laterotrusion, and retrusion.
      RESULTS: Comparison of baseline and post-treatment findings revealed that none of
      the joints exhibited a treatment-induced deterioration in the disc-condyle
      relationship, while the relationship improved in five joints. After
      categorization of the joints according to groups according to disc position,
      metric analysis of the MR images showed significantly-improved post-treatment
      disc positions in the joints that had initially exhibited anterior disc
      displacement. Post-treatment findings for maximum-open mouth position,
      protrusion, and laterotrusion corresponded to the baseline values recorded before
      bite-jumping, and the extent of maximum active retrusion increased significantly.
      CONCLUSIONS: Functional jaw orthopedics for correction of skeletal Class II with
      the rigid fixed FMA leads to side-effects reflected in the disc-condyle
      relationship in the temporomandibular joints: no adverse effects were observed in
      joints presenting an initial physiological disc-condyle relationship, whereas the
      disc position may improve in joints with initial partial or total anterior disc
      displacement. In comparison with the baseline findings, we observed no post
      treatment restriction in the extent of maximum mouth opening, protrusion, and
      left and right laterotrusion. Maximum active retrusion increased due to the
      treatment. MR imaging and MSA only partly cover the same aspects of
      temporomandibular joint diagnostics.

PMID- 16953356
TI  - Interdisciplinary cooperation exemplified by two complex cases of enamel erosion.
AB  - OBJECTIVE: Students of the Frankfurt am Main University Hospital participate in
      an interdisciplinary instructional unit in which they are presented with complex
      interdisciplinary findings and previous diagnostic records that are discussed in
      the patient's presence. We have recently observed a growing number of patients
      presenting defects of dental hard tissue in the form of erosions, defined as a
      loss of dental hard tissue due to the frequent and direct effect of acids not
      involving micro-organisms. These patients also presented marked malocclusions.
      For the most part, the diagnoses involve operative dentistry, dental prosthetics,
      orthodontics, oral, maxillofacial and plastic surgery. The clinicians discuss
      causes and therapeutic alternatives, at which point the therapeutic course is
      determined in consultation with the patient. CASE HISTORIES: We present herein
      two exemplary cases complex in etiology, as well as in treatment planning and
      realization. The case descriptions illustrate the importance of interdisciplinary
      agreement and cooperation in difficult courses of therapy, illustrating that, in
      the interest of the patient, it makes sense to establish interdisciplinary
      networks.

PMID- 16953357
TI  - A premolar extraction case using the Invisalign system.
AB  - INTRODUCTION: Invisalign therapy is an orthodontic treatment method using
      removable transparent polyurethane splints. Its applicability in extraction cases
      is limited. This case report documents the treatment with Invisalign of a patient
      in whom four premolars had to be extracted due to dental crowding. FINDINGS AND
      DIAGNOSIS: The patient's primary objective was to undergo treatment to resolve
      her anterior crowding as esthetically inconspicuously as possible. Diagnostic
      findings were: constriction of the maxillary and mandibular arch with anterior
      dental crowding; proclination and anteposition of the anteriors; neutroclusion
      with an overjet of 6 mm and an overbite of 1 mm. The radiographs showed a mesial
      tilt of the lower canines and premolars and a mild skeletal Class II relationship
      with a vertical craniofacial configuration. TREATMENT PROGRESS AND RESULTS:
      Treatment was initiated by extracting the four first premolars and placing the
      attachments (Tetric Ceram composite). After the Invisalign aligners had been
      worn, the anterior segment was uprighted and retracted, the crowding resolved,
      and the arches well-aligned. The patient's neutroclusion was maintained,
      physiological anterior relations in the sagittal and vertical planes were
      achieved, and the lower canines and premolars were uprighted. Active treatment
      lasted 1 year and 8 1/2 months and involved 43 maxillary and 28 mandibular
      aligners. CONCLUSION: Particularly in cases with an extended indication for this
      new treatment modality, due consideration must be given to the importance of
      comprehensive and meticulous diagnostics and treatment planning, and a solid
      grasp of the biological and mechanical fundamentals.

PMID- 16953358
TI  - [When a broken finger causes cold sweat].

PMID- 16953359
TI  - [Health and migration. Psychosocial determinants].
AB  - The article provides an overview of the contemporary literature on the social and
      psychological factors which are associated with migration. Derived from the
      operationalisation of "migration" and an examination of the methodological
      peculiarities of migration research, a (transactional) stress model of migration
      is proposed incorporating potentially stress-eliciting influences of migration
      including occupational pressures, social isolation and/or family-related problems
      and their impact on psychological and physical health. There are inconsistencies
      in the findings regarding psychological health, which can in part be explained
      through the phenomena of the "healthy migrant effect", duration of stay in the
      host culture or the culture-specificity. Moreover, a discussion is provided of
      the extent that disorders associated with differentially stressed migrants will
      be manifested in the health care system. Finally, concluding remarks are offered
      together with a short discussion of the implication of these findings for future
      research and social and health policy decision-making.

PMID- 16953360
TI  - [A regulatory view on the article: Risk evaluation of carcinogens and their
      threshold levels, part I-III].

PMID- 16953361
TI  - [Sanitation requirements concerning baths and their observation. Recommendations
      of the Federal Environmental Agency after Hearings of the Swimming and Bath Basin
      Water Commission of the Federal Ministry for Health in the Federal Environmental
      Office].

PMID- 16953363
TI  - [Procedure of Look Back (pursuant to 19 Transfusion Law). At the 62nd meeting of
      the Work Group Blood on June 14, 2006 the following vote (V 34) was passed].

PMID- 16953366
TI  - Effects of 28 days of beta-alanine and creatine monohydrate supplementation on
      aerobic power, ventilatory and lactate thresholds, and time to exhaustion.
AB  - The effect of beta-alanine (beta-Ala) alone or in combination with creatine
      monohydrate (Cr) on aerobic exercise performance is unknown. The purpose of this
      study was to examine the effects of 4 weeks of beta-Ala and Cr supplementation on
      indices of endurance performance. Fifty-five men (24.5 +/- 5.3 yrs) participated
      in a double-blind, placebo-controlled study and randomly assigned to one of 4
      groups; placebo (PL, n = 13), creatine (Cr, n = 12), beta-alanine (beta-Ala, n =
      14), or beta-alanine plus creatine (CrBA, n = 16). Prior to and following
      supplementation, participants performed a graded exercise test on a cycle
      ergometer to determine VO(2peak), time to exhaustion (TTE), and power output,
      VO(2), and percent VO(2peak) associated with VT and LT. No significant group
      effects were found. However, within groups, a significant time effect was
      observed for CrBa on 5 of the 8 parameters measured. These data suggest that CrBA
      may potentially enhance endurance performance.

PMID- 16953367
TI  - p21WAF1/CIP1 and 14-3-3 sigma gene expression in degenerated aortic valves: a
      link between cell cycle checkpoints and calcification.
AB  - The mechanisms underlying aortic valve degeneration are largely unknown. Cardiac
      tissue responds to a variety of stimuli by hypertrophic growth. Molecular
      mechanisms resulting in the hypertrophic response indicate similarity and overlap
      with those involved in both cell growth and death. We hypothesized cell cycle
      control to be the key event in progression regulation of heart valve degeneration
      followed by tissue mineralization. Human post-operative tissue samples of native
      non-rheumatic stenosed aortic valves were categorized according to absence (group
      1) or presence of calcification (group 2). The samples were ex vivo examined for
      cell density and presence of macrophage (CD68), as well as expression of two
      checkpoint genes, p21WAF1/CIP1 and 14-3-3 sigma, arresting the G1 and G2 cell
      cycle phases, respectively. Expression rates were measured by "Real-Time"-PCR on
      transcriptional level. Target protein expression was measured and their co
      localization in different kinds of valvular cells was tested using
      immunohistochemical analysis. Whereas macrophages were localized predominantly in
      sub-endothelial layer of valvular fibrosis, p21WAF1/CIP1 and 14-3-3 sigma
      expression was observed also in the valvular spongiosa co-localized with alpha
      actin positive cells. Significantly higher cell density and inflammation grade
      were observed in group 2 versus group 1. Accordingly, p21WAF1/CIP1 and 14-3-3
      sigma expression was several fold higher in group 1 versus group 2 on both
      transcription and translation levels. The present findings on degenerated aortic
      valves show that increased cell density accompanied with consequent calcification
      might be attributed to the down-regulation of both G1 and G2 checkpoint genes.

PMID- 16953371
TI  - Preterm birth due to maternal infection: Causative pathogens and modes of
      prevention.
AB  - Preterm birth represents a major problem for modern obstetrics due to its
      increasing frequency and the accompanying socioeconomic impact. Although several
      maternal characteristics related to preterm birth have been identified, the
      etiology in most cases remains inadequately understood. Various microorganisms
      have been linked to the pathogenesis of preterm birth. Microbes may reach the
      amniotic cavity and fetus by ascending from the vagina and cervix, by
      hematogenous distribution through the placenta, by migration from the abdominal
      cavity through the fallopian tubes, or through invasive medical procedures.
      Organisms commonly cultured from the amniotic cavity following preterm delivery
      include Ureaplasma urealyticum, Mycoplasma hominis, Bacteroides spp., Gardnerella
      vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis,
      and group B hemolytic streptococci. Several trials have examined the effect of
      antibiotic administration to patients with preterm labor and intact membranes,
      preterm premature rupture of the membranes, genital mycoplasmal infection,
      asymptomatic bacteriuria, and bacterial vaginosis. The results of such studies,
      which were variable and often conflicting, are discussed here.

PMID- 16953372
TI  - Diagnostic value of ECG-gated multidetector computed tomography in the early
      phase of suspected acute myocarditis. A preliminary comparative study with
      cardiac MRI.
AB  - The aim of the study was to determine the potential diagnostic value of contrast
      enhanced echocardiogram (ECG)-gated multidetector computed tomography (MDCT) in
      the setting of suspected acute myocarditis compared with contrast-enhanced
      magnetic resonance imaging (MRI). The study group consisted of 12 consecutive
      patients admitted for suspected acute myocarditis less than 10 days after onset
      of symptoms. All patients had clinical, electrocardiographic signs, and
      laboratory findings consistent with the diagnosis. All patients but one (severe
      claustrophobia) underwent cardiac MRI using T1-weighted delayed-enhancement
      images after injection of gadolinium. ECG-gated MDCT was performed in all
      patients and included a first-pass contrast-enhanced acquisition and a delayed
      acquisition. MRI revealed abnormal focal or multifocal myocardial enhancement and
      confirmed the diagnosis in 11 patients. The first-pass MDCT acquisition showed
      homogenous left-ventricle contrast enhancement and absence of coronary stenosis
      in all patients. Delayed MDCT acquisition, performed 5 min later without
      reinjection of contrast medium revealed multiple areas of myocardial
      hyperenhancement in a focal or a multifocal pattern (six and six patients,
      respectively). Extent and location of hyperenhancement at MDCT correlated well
      with that observed at MR examination for all 11 patients evaluated by both
      techniques (r=0.9167, p=0.0004). These preliminary results show that ECG-gated
      MDCT could be a useful alternative noninvasive diagnostic test in the early phase
      of acute myocarditis.

PMID- 16953373
TI  - Understanding multislice CT urography techniques: Many roads lead to Rome.
AB  - CT urography has emerged as a serious alternative to conventional urography by
      utilizing the advantages of modern multislice CT techniques for the visualization
      of the entire upper urinary tract. Several different examination techniques have
      been developed in multislice CT (MSCT) urography for improving the opacification
      and distension of the urinary tract. All efforts in performing MSCT urography
      have to compromise between the best possible image quality and a reasonably low
      radiation exposure. Initial low-dose examination protocols are already available.
      Operating modern MSCT urography properly is not difficult, but it presupposes
      basic knowledge on the variety of current MSCT urography techniques, including
      such issues as present-day indications, split-bolus injection, compression,
      saline infusion, low-dose diuretic administration, hybrid scanning, timing of the
      acquisition delay, examination protocols, postprocessing, image analysis, and
      radiation exposure. This article is not intended to provide guidelines of how to
      conduct MSCT urography, but everyone will be able to understand the functionality
      of several robust operating MSCT urography techniques, which helps making an
      individual selection for the clinical practice. In the near future, systematic
      studies are awaited evaluating the morphologic and diagnostic accuracy of MSCT
      urography regarding diverse urinary tract disorders.

PMID- 16953374
TI  - Digital X-ray radiogrammetry better identifies osteoarthritis patients with a low
      bone mineral density than quantitative ultrasound.
AB  - This study assessed the ability of quantitative ultrasound (QUS) and digital X
      ray radiogrammetry (DXR) to identify osteopenia and osteoporosis in patients with
      knee osteoarthritis (OA). One hundred and sixty-one patients with painful knee OA
      (81 men, 80 women; age 62.6+/-9.2 years, range 40-82 years) were included in this
      cross-sectional study and underwent dual-energy X-ray absorptiometry (DXA) of
      both hips and the lumbar spine, QUS of the phalanges and calcanei of both hands
      and heels, and DXR using radiographs of both hands. Unpaired t-test, Mann-Whitney
      U test, ROC analysis and Spearman's rank correlation were used for comparisons
      and correlation of methods. Using DXA as the reference standard, we defined a low
      bone mineral density (BMD) as a T-score < or =-1.0 at the lumbar spine or
      proximal femur. In contrast to phalangeal or calcaneal QUS, DXR was able to
      discriminate patients with a low BMD at the lumbar spine (p<0.0001) or hips
      (p<0.0001). ROC analysis showed that DXR had an acceptable predictive power in
      identifying OA patients a low hip BMD (sensitivity 70%, specificity 71%).
      Therefore, DXR used as a screening tool could help in identifying patients with
      knee OA for DXA.

PMID- 16953375
TI  - Facial infiltrative lipomatosis.
AB  - BACKGROUND: Although there are multiple case reports and small series concerning
      facial infiltrative lipomatosis, there is no composite radiological description
      of the condition. OBJECTIVE: Radiological evaluation of facial infiltrative
      lipomatosis using plain film, sonography, CT and MRI. MATERIALS AND METHODS: We
      radiologically evaluated four patients with facial infiltrative lipomatosis.
      Initial plain radiographs of the face were acquired in all patients. Three
      children had an initial sonographic examination to evaluate the condition,
      followed by MRI. One child had a CT and then MRI. RESULTS: One child had
      abnormalities on plain radiographs. Sonographically, the lesions were seen as ill
      defined heterogeneously hypoechoic areas with indistinct margins. On CT images,
      the lesions did not have a homogeneous fat density but showed some relatively
      more dense areas in deeper parts of the lesions. MRI provided better delineation
      of the exact extent of the process and characterization of facial infiltrative
      lipomatosis. CONCLUSION: Facial infiltrative lipomatosis should be considered as
      a differential diagnosis of vascular or lymphatic malformation when a child
      presents with unilateral facial swelling. MRI is the most useful single imaging
      modality to evaluate the condition, as it provides the best delineation of the
      exact extent of the process.

PMID- 16953376
TI  - Hyaline vascular Castleman disease associated with POEMS syndrome and cerebral
      infarction.

PMID- 16953377
TI  - Concentrated urine and diluted urine: the effects of citrate and magnesium on the
      crystallization of calcium oxalate induced in vitro by an oxalate load.
AB  - Supplementation of certain calcium crystallization inhibitors, such as citrate
      and magnesium, and the dilution of urine with water are now considered
      consolidated practice for the prevention of calcium kidney stones. The aim of
      this study is to verify, using tried and true in vitro methods, whether the
      effect of these inhibitors can manifest itself in different ways depending on
      whether the urine is concentrated or diluted. Calcium oxalate crystallization was
      studied on 4-h urine of 20 male idiopathic calcium oxalate stone formers, first
      under low hydration conditions (non-diluted urine) and then under high hydration
      conditions (diluted urine). Both the diluted and the non-diluted urine samples
      were subjected to three types of load: (a) an oxalate concentration increment of
      1.3 mmol/l only; (b) an oxalate concentration increment of 1.3 mmol/l with a
      citrate concentration increment of 1.56 mmol/l; (c) an oxalate concentration
      increment of 1.3 mmol/l with a magnesium concentration increment of 2.08 mmol/l.
      In non-diluted urine, the addition of the citrate and magnesium did not modify
      the crystallization parameters under study. In contrast, in the diluted urine the
      addition of the citrate and magnesium led to a reduction in the total quantity of
      crystals (equivalent to 35-45%) and their aggregates (equivalent to 30-40%); at
      the same time, there was an increase in the diameter of the monohydrate calcium
      oxalate crystals, which also underwent a morphological change. In conclusion, the
      inhibitory effects of citrate and magnesium on the crystallization of calcium
      oxalate do not manifest themselves in highly concentrated urine.

PMID- 16953378
TI  - [Pathology in Third World countries. Experience in Cambodia ].

PMID- 16953379
TI  - Offspring birthweight is not associated with paternal insulin resistance.
AB  - AIMS/HYPOTHESIS: Low birthweight is associated with insulin resistance and other
      insulin resistance-related phenotypes: diabetes, hypertension, and vascular
      disease in later life. The underlying mechanism is unclear. The foetal insulin
      hypothesis proposes that a single genetic predisposition to beta cell
      dysfunction/insulin resistance results in both reduced insulin-dependent foetal
      growth in utero, hence low birthweight, and predisposition to type 2 diabetes.
      The aim of this study was to test whether, as predicted by the foetal insulin
      hypothesis, there is an association between measures of paternal insulin
      resistance and offspring birthweight. SUBJECTS AND METHODS: The Exeter Family
      Study of Childhood Health (EFSOCH) is a community-based study within central
      Exeter (UK), established to test the foetal insulin hypothesis prospectively.
      Associations were tested between offspring birthweight and paternal insulin
      resistance, calculated by homeostasis model assessment analysis in 986 families
      using data relating to singleton, non-diabetic, UK white pregnancies. Ethics
      approval was given by the North and East Devon local ethics committee. RESULTS:
      Offspring birthweight was not significantly correlated with log paternal insulin
      resistance (r=0, p=0.91), log HDL cholesterol concentration (r=-0.02, p=0.47) or
      log triglyceride concentration (r=0, p=0.99) when corrected for paternal BMI and
      common confounders. Multiple linear regression analysis confirmed that paternal
      insulin resistance was not an independent predictor of offspring birthweight.
      CONCLUSIONS/INTERPRETATION: Results from a young, adult, non-diabetic population
      do not support the foetal insulin hypothesis as an explanation for the
      association of low birthweight with insulin resistance.

PMID- 16953380
TI  - Serotonin 1A receptor availability in patients with schizophrenia and schizo
      affective disorder: a positron emission tomography imaging study with [11C]WAY
      100635.
AB  - BACKGROUND: Postmortem and positron emission tomography (PET) studies have
      reported several alterations in serotonin 1A receptor (5-HT(1A)) binding
      parameters in patients with schizophrenia. This study examines 5-HT(1A)
      availability in vivo in individuals with schizophrenia and schizo-affective
      disorder. MATERIALS AND METHODS: Twenty-two medication-free individuals with
      schizophrenia or schizo-affective disorder and 18 healthy subjects underwent PET
      scans with [(11)C]WAY 100635. Regional distribution volumes (V(T), in milliliters
      per gram) were derived using a two-tissue compartment kinetic model. Outcome
      measures for 5-HT(1A) availability included binding potential (BP) and the
      specific to nonspecific equilibrium partition coefficient (V(3)''). Eleven brain
      regions with high density of 5-HT(1A) were included in the analysis. RESULTS: No
      significant differences were observed in regional BP or V(3)'' between patients
      and controls. No significant relationships were observed between regional 5
      HT(1A) availability and symptom severity. CONCLUSION: The postmortem literature
      reports increased 5-HT(1A) binding in the prefrontal cortex in schizophrenia.
      This study did not detect differences in 5-HT(1A) binding. Whereas in two
      recently published PET studies, one reports increased binding in the temporal
      lobe while the other reports decreased binding in the amygdala. These
      inconsistencies suggest that the alterations demonstrated in postmortem studies
      cannot be reliably detected at the resolution achieved with PET. This raises the
      question as to whether major changes in the level of expression of the 5-HT(1A)
      receptor play a role in the pathophysiology of schizophrenia.

PMID- 16953381
TI  - Intramuscular aripiprazole for the treatment of acute agitation in patients with
      schizophrenia or schizoaffective disorder: a double-blind, placebo-controlled
      comparison with intramuscular haloperidol.
AB  - INTRODUCTION: This double-blind, placebo-controlled study investigated the
      efficacy and safety of intramuscular (IM) aripiprazole and IM haloperidol for the
      treatment of acute agitation in patients with schizophrenia or schizoaffective
      disorder. MATERIALS AND METHODS: Four-hundred and forty-eight patients were
      randomized (2:2:1 ratio) to IM aripiprazole 9.75 mg, IM haloperidol 6.5 mg, or IM
      placebo. Patients could receive up to three injections over the first 24 h, with
      second and third injections administered > or =2 and > or =4 h, respectively,
      after the first if deemed clinically necessary. Primary efficacy measure was mean
      change in Positive and Negative Syndrome Scale Excited Component (PEC) score from
      baseline to 2 h. RESULTS: Mean improvement in PEC at 2 h was significantly
      greater for IM aripiprazole (-7.27) vs placebo (-4.78; p<0.001); IM aripiprazole
      was noninferior to IM haloperidol (-7.75) on PEC. All secondary efficacy measures
      showed significantly greater improvements at 2 h for IM aripiprazole and IM
      haloperidol over placebo. Mean number of injections/patient and percentage of
      patients requiring benzodiazepines were significantly lower for IM aripiprazole
      vs placebo (p<0.01). IM aripiprazole was well tolerated. Extrapyramidal symptom
      related adverse events were similar for aripiprazole (1.7%) and placebo (2.3%)
      and lower than with haloperidol (12.6%). CONCLUSION: These results show that IM
      aripiprazole is an effective treatment, comparable to IM haloperidol, and well
      tolerated for acute agitation in patients with schizophrenia.

PMID- 16953382
TI  - Alcohol effects on inhibitory control of attention: distinguishing between
      intentional and automatic mechanisms.
AB  - RATIONALE: Recent research has begun to explore the possibility that inhibitory
      mechanisms of selective attention are particularly susceptible to the impairing
      effects of moderate doses of alcohol. However, literature also suggests that
      automatic processes might be more resistant to this impairing effect than
      controlled processes. OBJECTIVE: The present study used a delayed ocular response
      task and a saccadic interference task to examine the effects of alcohol on both
      intentionally controlled and automatic inhibitory influences on selective
      attention. MATERIALS AND METHODS: Twelve healthy adults performed both tasks
      under three doses of alcohol (0.0, 0.45, and 0.65 g/kg). RESULTS: The results
      showed that alcohol reduced intentional inhibitory control over selective
      attention but had no effect on automatic inhibitory influences. CONCLUSION: The
      present investigation marks the first effort to directly compare alcohol effects
      on automatic and intentional inhibitory mechanisms of visual attention. The
      results suggest that attentional processes dependent on intentional inhibitory
      control may be more susceptible to the impairing effects of a moderate dose of
      alcohol than processes dependent on automatic inhibition.

PMID- 16953383
TI  - Effects of aripiprazole on operant responding for a natural reward after
      psychostimulant withdrawal in rats.
AB  - RATIONALE: Withdrawal from repeated amphetamine administration has been shown to
      decrease the motivation to work for a natural reward in rats, a phenomenon
      thought to be associated with hypofunction of the mesolimbic dopamine system.
      OBJECTIVES: We tested whether aripiprazole, a partial dopamine receptor agonist,
      can restore the animals' responding for reward pellets after amphetamine
      withdrawal. MATERIALS AND METHODS: Rats were trained to lever-press for food
      pellets under a progressive ratio-schedule of reinforcement. After reaching a
      stable breakpoint, i.e., the highest ratio completed, one group was injected ten
      times with increasing doses of amphetamine (1 to 10 mg/kg, three times a day for
      4 days), while the other group received vehicle injections. The rats were again
      tested for their breakpoint 24 h after the last amphetamine injection under 0.0,
      0.25, 0.75, and 2.5 mg/kg aripiprazole. RESULTS: Withdrawal from repeated
      amphetamine injection reduced the breakpoint while low doses of aripiprazole
      (0.25 and 0.75 mg/kg) prevented this effect. In addition, the rats needed a
      longer time for the first 20 pellets (fixed ratio-schedule training before
      starting the progressive ratio-schedule) after amphetamine withdrawal but not
      after subsequent injection with aripiprazole. It is notable that the injection of
      2.5 mg/kg aripiprazole reduced responding for reward pellets and prolonged the
      duration for the first 20 pellets irrespective of previous amphetamine or vehicle
      treatment. However, withdrawal from repeated administration of 0.25 and 2.5 mg/kg
      aripiprazole did not reduce responding for reward pellets. CONCLUSIONS: These
      results suggest that aripiprazole may have potential use as a treatment for the
      motivational effects of the acute withdrawal stage of the psychostimulant
      addiction cycle.

PMID- 16953384
TI  - Discriminative stimulus functions of AM-1346, a CB1R selective anandamide analog
      in rats trained with Delta9-THC or (R)-methanandamide (AM-356).
AB  - OBJECTIVE: To characterize in vivo the high-affinity cannabinoid CB1 receptor
      (CB1R) selective anandamide analog AM-1346 [alkoxyacid amide of N-eicosa
      tetraenylamine] using drug discrimination procedures. D-amphetamine and also
      morphine in the (R)-methanandamide-trained group (see below) were examined to
      assess pharmacological specificity. METHODS: Three groups of rats were trained to
      discriminate between vehicle and (1) 1.8 mg/kg Delta9-tetrahydrocannabinol
      (Delta9-THC); (2) 5.6 mg/kg Delta9-THC; and (3) 10 mg/kg (R)-methanandamide (AM
      356; a metabolically stable analog of anandamide). Delta9-THC was given i.p. 30
      min and (R)-methanandamide 15 min before training. RESULTS: AM-1346 generalized
      to all three training conditions, both at 15 and 30 min after administration. The
      rank order potency was: Delta9-THC > AM-1346 > (R)-methanandamide. AM-1346
      appeared slightly more potent 30 min compared to 15 min postadministration. In
      the presence of 0.3 mg/kg of the CB1R antagonist/inverse agonist SR-141716A, the
      dose generalization curves of Delta9-THC and AM-1346 resulted in parallel shifts
      to the right in the 1.8 mg/kg Delta9-THC-trained group. A long duration of action
      for AM-1346 (relative to AM-356) was indicated in tests where AM-1346 was
      examined in the 5.6 mg/kg Delta9-THC-trained group. Neither D-amphetamine, nor
      morphine generalized in either of the groups, suggesting pharmacological
      specificity. CONCLUSION: Unlike (R)-methanandamide, the surmountable antagonism
      between SR-141716A and AM-1346 shows that the structural features of anandamide
      can be modified in ways that reduce the dissociation between the discriminative
      stimulus and rate decreasing effects of CB1R agonists derived from an anandamide
      template.

PMID- 16953385
TI  - Differences in orbitofrontal activation during decision-making between methadone
      maintained opiate users, heroin users and healthy volunteers.
AB  - OBJECTIVE: Previously, we reported that opiate users enrolled in methadone
      treatment made 'risky' choices on a decision-making task following a loss of
      points compared with heroin users and healthy volunteers. One possible
      explanation for this behaviour is that methadone users were less sensitive to
      punishment on immediately preceding unsuccessful trials. METHODS: We sought to
      explore this finding from a neural perspective by performing a post hoc analysis
      of data from a previous [see text] positron emission tomography study. We
      restricted the analysis to the opiate groups and controls, assessing differences
      between opiate users on methadone and those on heroin. RESULTS: We found
      significant over-activation in the lateral orbitofrontal cortex (OFC) in
      methadone users compared with both heroin users and controls concomitant with the
      greatest overall tendency to 'play risky'. Heroin users showed significant under
      activation in this area compared with the other two groups whilst exhibiting the
      greatest overall tendency to 'play safe'. Correlational analysis revealed that
      abnormal task-related activation of the left OFC was associated with the dose of
      methadone in methadone users and with the duration of intravenous heroin use in
      heroin users. 'Playing safe' following a loss of points was also negatively
      correlated with the activation of pregenual anterior cingulate and insula cortex
      in controls, but not in opiate users. CONCLUSION: Our findings suggest that the
      interplay between processes involved in integrating penalty information for the
      purpose of response selection may be altered in opiate users. This change was
      reflected differentially in task-related pattern of OFC activation depending on
      the opiate used.

PMID- 16953386
TI  - Conditional CRF receptor 1 knockout mice show altered neuronal activation pattern
      to mild anxiogenic challenge.
AB  - RATIONALE: Regional-specific corticotropin-releasing factor receptor 1 (CRF-R1)
      knockout mice have been generated recently as a tool to dissociate CNS functions
      modulated by this receptor. In these mice, CRF-R1 function is postnatally
      inactivated in the anterior forebrain including limbic brain structures but not
      in the pituitary leading to normal activity of the hypothalamic-pituitary
      adrenocortical (HPA) axis under basal conditions and reduced anxiety-related
      behavior in the light-dark box and the elevated plus maze (EPM) as compared to
      wild-type (WT) mice (Muller et al., Nat Neurosci 6:1100-1107, 2003). OBJECTIVE:
      To identify neurobiological correlates underlying this reduced anxiety-like
      behavior, the expression of c-Fos, an established marker for neuronal activation,
      which was examined in response to a mild anxiogenic challenge. MATERIALS AND
      METHODS: Mice were placed for 10 min on the open arm (OA) of the EPM, and
      regional c-Fos expression was investigated by immunohistochemistry. RESULTS: OA
      exposure enhanced c-Fos expression in both conditional CRF-R1 knockout and WT
      mice in a number of brain areas (39 of 55 quantified), including cortical,
      limbic, thalamic, hypothalamic, and hindbrain regions. The c-Fos response in
      conditional CRF-R1 knockout animals was reduced in a restricted subset of
      activated neurons (4 out of 39 regions) located in the medial amygdala, ventral
      lateral septum, prelimbic cortex, and dorsomedial hypothalamus. CONCLUSIONS:
      These results underline the importance of limbic CRF-R1 in modulating anxiety
      related behavior and suggest that reduced neuronal activation in the identified
      limbic and hypothalamic key structures of the anxiety circuitry may mediate or
      contribute to the anxiolytic-like phenotype observed in mice with region-specific
      deletion of forebrain CRF-R1.

PMID- 16953387
TI  - Confirmation of quantitative trait loci for ethanol sensitivity and neurotensin
      receptor density in crosses derived from the inbred high and low alcohol
      sensitive selectively bred rat lines.
AB  - RATIONALE: Genetically influenced alcohol sensitivity is thought to be an
      important risk factor for the development of alcoholism. An effective first step
      for identifying genes that mediate variation in alcohol sensitivity is through
      quantitative trait loci (QTL) mapping in model organisms. OBJECTIVE: Fourteen
      provisional QTLs related to alcohol sensitivity were previously mapped in an F2
      derived from the IHAS1 and ILAS1 rat lines. The objective of the current study
      was to confirm those QTLs in an independently derived F2 and in congenics that
      were bred for two of the loci. MATERIALS AND METHODS: IHAS1 X ILAS1 F2 (n=450)
      were tested for alcohol-induced loss of righting reflex (LORR), blood ethanol
      concentration at regain of righting reflex (BECRR), sensitivity and acute
      tolerance on the Rotarod, and neurotensin receptor density (NTR1). Rats were
      genotyped at the 14 candidate loci and QTL mapping was conducted. Reciprocal
      congenic strains were bred for loci on chromosomes 2 and 5 and tested for LORR
      and BECRR. RESULTS: Four LORR QTLs were mapped at the suggestive or significant
      level (chromosomes 2, 5, 12, and 13). BECRR was mapped to chromosomes 5, 12, and
      13 either in the original or current experiment. Results of the congenic
      experiment also support QTLs for LORR and BECRR on chromosomes 2 and 5. QTLs for
      NTR1 density and behavior on the Rotarod were not confirmed. CONCLUSIONS: QTL
      mapping in crosses derived from the IHAS1 and ILAS1 has successfully identified
      loci related to alcohol sensitivity. Recombinant congenics are now being bred to
      more finely map the confirmed QTLs.

PMID- 16953391
TI  - A comparison of the concentration-effect relationships of PAHs on CYP1A induction
      in HepG2 and Mcf7 cells.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants. Some
      compounds belonging to this group are considered carcinogenic to people. In order
      to yield carcinogenic properties, these compounds must be metabolically
      transformed by enzymes of cytochrome P450 family to oxy-derivatives. In this
      study, the ability of the following six PAHs: anthracene (Ant), benz(a)anthracene
      (BA), naphthacene (Nap), benzo(a)pyrene (BaP), dibenz(a,c)anthracene (DB(a,c)A)
      and dibenz(a,h)anthracene (DB(a,h)A) to induce enzymes of cytochrome P450
      (CYP450), in particular CYP1A1 and CYP1A2 in Mcf7 and HepG2 cells was studied.
      The induction of CYP1A enzymes was assessed at the level of enzymatic protein and
      enzymatic activity. The change in CYP1A1 and CYP1A2 protein level was assessed by
      means of confocal microscopy. The ethoxyresorufin-O-deethylase (EROD) and
      methoxyresorufin-O-deethylase (MROD) assays were applied to determine the CYP1A1
      and CYP1A2 activity. The Induction Equivalency Factors (IEFs) were also
      determined. According to EROD and MROD assay and calculated IEFs the following
      order of the inducing potency was determined in HepG2 cells: DB(a,h)A > BaP >
      DB(a,c)A approximately BA > Nap > Ant, and in Mcf7 cells: DB(a,h)A > DB(a,c)A >
      BaP > Nap > BA > Ant. The assessment of the protein levels revealed that DB(a,h)A
      was also the strongest inducer of protein level, however the correlation between
      enzymatic activity and protein level induction by other PAHs was not always
      evident. The EROD and MROD activities were higher in Mcf7 than in HepG2 cells,
      however the CYP1A2 protein level was shown to be higher in HepG2 cells. The
      results obtained indicate possible catalytic enzymatic activity alterations
      induced by PAHs.

PMID- 16953389
TI  - Discriminative stimulus effects of the cannabinoid CB1 antagonist SR 141716A in
      rhesus monkeys pretreated with Delta9-tetrahydrocannabinol.
AB  - RATIONALE: Drug discrimination can be used to examine tolerance and dependence in
      agonist-treated animals by establishing an appropriate antagonist as a
      discriminative stimulus. OBJECTIVE: Establish intravenous SR 141716A as a
      discriminative stimulus in four rhesus monkeys pretreated with a relatively small
      dose of Delta9-tetrahydrocannabinol (Delta9-THC). METHODS: Rhesus monkeys
      received i.v. Delta9-THC (0.32 mg/kg) and discriminated i.v. SR 141716A (1 mg/kg)
      from vehicle while responding under a fixed ratio (FR) 5 schedule of stimulus
      shock termination. RESULTS: The discriminative stimulus effects of SR 141716A
      were dose-dependent (ED50=0.33 mg/kg) and were mimicked by the CB1 antagonist AM
      251 (ED50=0.98 mg/kg), but not by a benzodiazepine (midazolam) or an N-methyl-D
      aspartate antagonist (ketamine). An additional dose (0.32 mg/kg in addition to
      0.32 mg/kg administered before the session) of Delta9-THC shifted the SR 141716A
      dose-effect curve 3-fold rightward. Omitting Delta9-THC before test sessions
      resulted in responding on the SR 141716A lever that was attenuated by subsequent
      administration of Delta9-THC (ED50=0.13 mg/kg), CP 55940 (ED50=0.013 mg/kg), and
      WIN 55212-2 (ED50=0.35 mg/kg); midazolam and ketamine did not attenuate
      responding on the SR 141716A lever. SR 141716A (1 mg/kg) shifted the Delta9-THC
      and CP 55940 dose-effect curves 3.4-fold rightward; the WIN 55212-2 dose-effect
      curve was not significantly modified by a dose of 1 mg/kg of SR 141716A.
      CONCLUSIONS: SR 141716A can be established as a discriminative stimulus in
      animals pretreated with Delta9-THC, and this assay is selective for cannabinoid
      activity. Differential antagonism of cannabinoids by SR 141716A might indicate
      that the mechanism of action of WIN 55212-2 is not identical to other
      cannabinoids. This study demonstrates that, under the appropriate conditions,
      drug discrimination has utility for examining cannabinoid dependence and
      withdrawal.

PMID- 16953390
TI  - The relationship between level of cigarette consumption and latency to the onset
      of retrospectively reported withdrawal symptoms.
AB  - RATIONALE: Subthreshold smokers (who smoke < or =5 cigarettes/day) experience
      withdrawal symptoms, yet they smoke less than is required to maintain serum
      nicotine levels. OBJECTIVES: For study 1, our aim was to determine (1) if adult
      subthreshold smokers report withdrawal symptoms; (2) how they rate symptom
      severity; (3) the length of their latency to withdrawal symptoms; (4) and the
      relationship between level of cigarette consumption and latency to withdrawal.
      The aim of study 2 was to attempt to replicate the results of study 1 in a
      nationally representative sample and to compare subthreshold and threshold (> or
      =6 cigarettes/day) smokers. METHODS: Study 1 was conducted through telephone
      interviews. Study 2 was conducted through secondary analysis of data from the
      National Youth Tobacco Survey (self-administered in schools). RESULTS: In study
      1, all subjects experienced withdrawal symptoms. The mean number of symptoms was
      4.3; mean intensity of each symptom was >6 (1-10 scale). A quarter of the
      subjects could go for > or =2 days before experiencing withdrawal. More frequent
      smokers had a shorter latency to withdrawal (r=-0.43, p<0.001, n=36). In study 2,
      63% of subthreshold smokers reported feeling at least one withdrawal symptom.
      Median latency to withdrawal was 168 h for subthreshold and 2 h for threshold
      smokers. A negative correlation between level of cigarette consumption and
      latency to withdrawal was observed for both groups. CONCLUSIONS: Although
      subthreshold smokers experience significant withdrawal symptoms, they can smoke
      infrequently because symptoms may not appear for one to several days. Consistent
      with the sensitization-homeostasis theory, low doses of nicotine can suppress
      withdrawal symptoms over long periods.

PMID- 16953388
TI  - Effects of endocannabinoid neurotransmission modulators on brain stimulation
      reward.
AB  - RATIONALE: The endogenous cannabinoid system is responsive to the neurobiological
      actions of Delta9-tetrahydrocannabinol (THC) and other cannabinoid ligands. While
      numerous studies have focused on the behavioral and pharmacological effects of
      THC and cannabinoid agonists in experimental animals, most recent work focuses on
      compounds that modulate endocannabinoid neurotransmission. However, the relevant
      studies concerning the ability of endocannabinoid modulators to modify reward
      processes in experimental animals remain rather scarce. OBJECTIVES: The present
      study examined the effects of drugs modulating endocannabinoid neurotransmission
      on brain reward function using the rate-frequency curve shift paradigm of
      intracranial self-stimulation (ICSS). METHODS: Animals were implanted with
      electrodes into the medial forebrain bundle (MFB). After brain stimulation reward
      thresholds stabilized, rats received intraperitoneal injections of the fatty acid
      amide hydrolase (FAAH) inhibitors phenylmethylsulfonyl fluoride (PMSF) (0, 15,
      30, and 60 mg/kg) and URB-597 (0, 0.3, 1, and 3 mg/kg) and the selective
      anandamide reuptake inhibitor OMDM-2 (0, 3, 10, and 30 mg/kg). RESULTS: The
      highest dose of URB-597 and OMDM-2 significantly increased the threshold
      frequency required for MFB ICSS, while PMSF increased the threshold frequency in
      all doses tested. The cannabinoid 1 (CB1) receptor antagonist SR141716A reversed
      the actions of URB-597 and OMDM-2, but not PMSF, without affecting reward
      thresholds by itself. CONCLUSIONS: These results indicate that under the present
      experimental conditions endocannabinoid modulators do not exhibit reinforcing
      properties, but rather have inhibitory influence on reward processes. The
      anhedonic effects of URB-597 and OMDM-2, but not PMSF, observed at the highest
      doses in this study are probably mediated through direct CB1 receptor
      stimulation.

PMID- 16953392
TI  - Plasma and cerebrospinal fluid pharmacokinetics of nelarabine in nonhuman
      primates.
AB  - INTRODUCTION: Nelarabine is a water-soluble prodrug of the cytotoxic
      deoxyguanosine analog ara-G, to which it is rapidly converted in vivo by
      adenosine deaminase. Nelarabine has shown activity in the treatment of T-cell
      malignancies, especially T-cell acute lymphoblastic leukemia. Preliminary data
      suggested that nelarabine might penetrate into the CSF. We therefore studied the
      CSF penetration of nelarabine and ara-G in a nonhuman primate model that has been
      highly predictive of anticancer drug distribution in humans. METHODS: Nelarabine
      (35 mg/kg, approximately 700 mg/m2) was administered over 1 h through a
      surgically implanted central venous catheter to four nonhuman primates. Blood
      (four animals) and ventricular CSF (three animals) samples were obtained at
      intervals for 24 h for determination of nelarabine concentrations, which were
      measured by HPLC-mass spectrometry. RESULTS: The nelarabine plasma AUC (median+/
      s.d.) was 2,820+/-1,140 microM min and the ara-G plasma AUC was 20,000+/-8,100
      microM min. The terminal half-life of nelarabine in plasma was 25+/-5.2 min and
      clearance was 42+/-61 ml/min/kg. The terminal half-life of ara-G in plasma was
      182+/-45 min. In CSF the terminal half-life of nelarabine was 77+/-28 min and of
      ara-G was 232+/-79 min. The AUCcsf:AUCplasma was 29+/-11% for nelarabine and 23+/
      12% for ara-G. CONCLUSION: The excellent CSF penetration of nelarabine and ara-G
      supports further study of the contribution of nelarabine to the prevention and
      treatment of CNS leukemia.

PMID- 16953393
TI  - Outcome of patients with reactive amyloidosis associated with rheumatoid
      arthritis in dialysis treatment.
AB  - The aim was to analyze the clinical outcome of a group of 51 patients diagnosed
      with systemic amyloidosis associated with rheumatoid arthritis who received
      hemodialysis (HD) as renal replacement therapy. We monitored the clinical course
      of the disease and factors that could influence survival. Determination of the
      onset of the underlying disorder was made retrospectively by reviewing the
      patient's chart when a diagnosis of amyloid was confirmed. During a 96.9 person
      year follow-up, 42 patients died. Survival of these 51 patients from the
      initiation of HD at 251 days was 50%. Poor prognosis in amyloid patients was
      mainly due to a large number of sudden deaths immediately following HD therapy.
      Out of 51 patients 21 needed unplanned initiation of HD. The unplanned initiation
      was significantly associated with poor survival. Seventy-five percentile of
      creatinine clearance (Ccr) was 9.7 ml/min, and 75% of these patients who
      initiated HD had highly impaired renal functional states. These data indicated
      that amyloidotic patients with HD showed a high mortality rate; therefore,
      planned initiation of HD was highly recommended to improve the patient's
      survival. Particular attention was given to the Ccr levels, because the levels of
      serum creatinine may not be a useful marker for some patients with amyloidosis.

PMID- 16953394
TI  - Effects of glucosamine administration on patients with rheumatoid arthritis.
AB  - The purpose of this study was to examine whether glucosamine has an antirheumatic
      effect in a randomized placebo-controlled study. The subjects were 51 rheumatoid
      arthritis (RA) patients: 25 patients in the glucosamine group and 26 patients in
      the placebo group. Glucosamine hydrochloride at a daily dose of 1,500 mg and
      placebo, respectively, were administered for 12 weeks along with conventional
      medication. While significant improvement was not found in joint counts and in
      the rate of ACR20 responders, the face scale and a visual analogue scale pain
      were significantly in favor of the glucosamine group. ESR and CRP levels did not
      change, but serum MMP-3 levels decreased in the glucosamine group. Results of the
      patients' self-evaluations and the physicians' global evaluations indicated that
      the glucosamine treatment produced noticeable improvements in symptoms. Although
      glucosamine administration had no antirheumatic effect evaluated by conventional
      measures, it seemed to have some symptomatic effects on RA.

PMID- 16953395
TI  - Estimation of direct unit costs associated with non-vertebral osteoporotic
      fractures in five European countries.
AB  - The objective of this study was to estimate the unit costs of non-vertebral
      osteoporotic fractures in five European countries based on the results of the
      SOTI and TROPOS clinical trials in postmenopausal osteoporotic women. The
      information recorded in the Case Report Forms was used. The perspective of third
      party payers was adopted. Hip fracture unit cost was the highest. The ranges of
      costs among countries was narrow for hip from 8,346 euros (Italy) to 9,907euros
      (France), but wider for other fractures: 890 euros (Spain) to 2,022 euros (Italy)
      for wrist, 1,167euros (Spain) to 3,268 euros (Italy) for pelvis, 837euros (Spain)
      to 2,116 euros (Italy) for sternum/clavicle, 565 euros (Spain) to 908 euros
      (France) for rib, 1,518 euros (Spain) to 3,651 euros (Belgium) for humerus, 1,805
      euros (Spain) to 3,521 euros (Italy) for leg. The costs of those fractures should
      be considered when estimating the cost of osteoporosis.

PMID- 16953398
TI  - An unusual cause of locking.
AB  - This case report describes the discovery of a plastic foreign body in a patient's
      knee joint 21 years from the initial injury. The patient was thoroughly
      investigated radiologically with plain X-rays both immediately after the initial
      injury and years later in orthopaedic outpatients. He also subsequently received
      an MRI. All these were reported as normal. The patient's symptoms persisted and
      an arthroscopy was performed. At this procedure the presence of the foreign body
      was confirmed and the offending plastic was safely removed. The patient's
      symptoms of intermittent locking resolved. This experience stresses this
      importance of clinical suspicion despite apparently normal radiology.

PMID- 16953396
TI  - Accelerated atherosclerosis in pre-menopausal female patients with rheumatoid
      arthritis.
AB  - Increased mortality due to cardiovascular disease in rheumatoid arthritis (RA)
      patients was reported. Using B-mode ultrasonography we compared intima-media
      thickness (IMT) and plaque occurrence (indicators of asymptomatic
      atherosclerosis) in the carotid arteries in 70 pre-menopausal, female RA patients
      and 40 controls. Correlations with different risk factors were evaluated. The IMT
      values were higher in RA patients (0.59 mm vs. 0.47 mm, P < 0.0001) and they had
      more plaques (P = 0.023). In RA patients higher levels of sensitive CRP (P <
      0.0001), ICAM (P < 0.0001), VCAM (P < 0.0001), IL-2 (P < 0.001), IL-6 (P = 0.009)
      and TNF-alfa (P < 0.01) were found. A correlation between IMT and triglycerides
      (P = 0.018) and a negative correlation between IMT and HDL cholesterol (P =
      0.037) were found. With multiple regression analysis the association between IMT
      and sensitive CRP (P = 0.027) and presence of plaques and apolipoprotein B (P =
      0.028) was established. The results indicate that even pre-menopausal, female RA
      patients had accelerated atherosclerosis. Chronic systemic inflammation may play
      an important role in atherogenesis.

PMID- 16953399
TI  - Electromyographic analysis in patients with multidirectional shoulder instability
      during pull, forward punch, elevation and overhead throw.
AB  - Multidirectional shoulder joint instability alters the role of dynamic
      stabilizers, as a result of which the motion patterns of the muscle around the
      shoulder joint are also changed. The aim of this study was to compare the muscle
      activity of patients with multidirectional shoulder instability and the control
      group during pull, forward punch, elevation and overhead throw. Fifteen subjects
      with multidirectional shoulder instability and fifteen control subjects with
      normal, healthy shoulders participated in the study. Both shoulders were tested
      in all subjects. Signals were recorded by surface EMG from eight different
      muscles during pull, forward punch, elevation and overhead throw. The mean and
      standard deviation of MVE% for the different movement types and time broadness
      values during overhead throw were determined for each muscle in both groups and
      compared with each other. Test results suggest that in case of patients with
      multidirectional shoulder instability the various motions are performed in a
      different way. The results give rise to the assumption that the centralization of
      the glenohumeral joint and the reduction of instability are attempted to be
      ensured by the organism through increasing the role of rotator cuff muscles and
      decreasing the role of the deltoid, biceps brachii and pectoralis maior muscles.
      The analysis of time broadness shows that in patients with multidirectional
      shoulder instability, the time difference between the peaks of normalized
      voluntary electrical activity is significantly greater than in the control group.

PMID- 16953400
TI  - Resolution recovery in pinhole SPECT based on multi-ray projections: a phantom
      study.
AB  - PURPOSE: Low sensitivity can become a major problem when very small pinholes are
      used in SPECT imaging. Although a larger pinhole aperture will improve the
      sensitivity, this will be at the cost of the spatial resolution. With a view to
      improving the resolution-sensitivity trade-off, this paper explores an iterative
      reconstruction algorithm that models the pinhole aperture based on multi-ray
      projections. METHODS: This new implementation was validated using simulated data
      and phantom experiments. Two approaches were investigated. Firstly, the pinhole
      aperture was modelled in both the forward and the back projector. Secondly, the
      dual matrix implementation was investigated by modelling the pinhole aperture
      only in the forward projector. The systematic error, the full-width at half
      maximum (FWHM) and the statistical error were quantified using the simulated
      data. Experimental phantom data were acquired for visual comparison with the
      reconstructions obtained from the simulated data. RESULTS: For a predefined
      number of iterations, the systematic error, the FWHM and the statistical error
      could be decreased when the pinhole aperture was modelled during iterative
      reconstruction. For a fixed, predefined statistical error of +/-10%, smaller
      systematic errors and smaller FWHM were obtained when modelling the pinhole
      opening. When the dual matrix implementation was used, equivalent results could
      be obtained as when modelling the pinhole opening in both the forward and the
      back projector. CONCLUSION: The multi-ray method to accomplish resolution
      recovery during the reconstruction of pinhole SPECT projection images offers a
      better trade-off between spatial resolution and noise compared with a
      reconstruction which does not model the pinhole aperture.

PMID- 16953401
TI  - Neutrophilic urticaria: whole-body (111)In-leukocyte scan and histological
      correlation.

PMID- 16953403
TI  - Abstracts from the Annual Congress of the European Association of Nuclear
      Medicine. October 1-3, 2006. Athens Greece.

PMID- 16953402
TI  - Standardised uptake values from PET/CT images: comparison with conventional
      attenuation-corrected PET.
AB  - PURPOSE: In PET/CT, CT-derived attenuation factors may influence standardised
      uptake values (SUVs) in tumour lesions and organs when compared with stand-alone
      PET. Therefore, we compared PET/CT-derived SUVs intra-individually in various
      organs and tumour lesions with stand-alone PET-derived SUVs. METHODS: Thirty-five
      patients with known or suspected cancer were prospectively included. Sixteen
      patients underwent FDG PET using an ECAT HR+scanner, and subsequently a second
      scan using a Biograph Sensation 16PET/CT scanner. Nineteen patients were scanned
      in the reverse order. All images were reconstructed with an iterative algorithm
      (OSEM). Suspected lesions were grouped as paradiaphragmatic versus distant from
      the diaphragm. Mean and maximum SUVs were also calculated for brain, lung, liver,
      spleen and vertebral bone. The attenuation coefficients (mu values) used for
      correction of emission data (bone, soft tissue, lung) in the two data sets were
      determined. A body phantom containing six hot spheres and one cold cylinder was
      measured using the same protocol as in patients. RESULTS: Forty-six lesions were
      identified. There was a significant correlation of maximum and mean SUVs derived
      from PET and PET/CT for 14 paradiaphragmatic lesions (r=0.97 respectively;
      p<0.001 respectively) and for 32 lesions located distant from the diaphragm
      (r=0.87 and r=0.89 respectively; p<0.001 respectively). No significant
      differences were observed in the SUVs calculated with PET and PET/CT in the
      lesions or in the organs. In the phantom, radioactivity concentration in spheres
      calculated from PET and from PET/CT correlated significantly (r=0.99; p<0.001).
      CONCLUSION: SUVs of cancer lesions and normal organs were comparable between PET
      and PET/CT, supporting the usefulness of PET/CT-derived SUVs for quantification
      of tumour metabolism.

PMID- 16953414
TI  - Percutaneous endoscopic discectomy and drainage for infectious spondylitis.
AB  - Fifteen patients with infectious spondylitis were treated by percutaneous
      endoscopic discectomy and drainage (PEDD) and associated appropriate parenteral
      antibiotics. Infectious spondylitis was diagnosed clinically, on the basis of
      elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
      values, and on roentgenographic and magnetic resonance imaging (MRI) findings.
      Causative bacteria were identified in 13 (86.7%) of 15 biopsy specimens. Systemic
      antibiotics were administered according to sensitivity analyses of pathogens. All
      patients reported immediate back pain relief except for two, who required
      anterior debridement and fusion one week and two weeks later, respectively. Two
      other patients with recurrent infection and intractable pain underwent surgical
      intervention at one month and eight months after PEDD, respectively. The
      remaining 11 patients recovered uneventfully after full-course, specific,
      antimicrobial therapy. No surgery related complications or side effects were
      observed during at least 12 months of follow-up. In conclusion, PEDD can provide
      retrieval of sufficient specimens and has high diagnostic efficacy, thereby
      enabling prompt and appropriate antibiotic therapy to the offending pathogens. It
      can be considered an effective alternative for treating uncomplicated
      spondylitis.

PMID- 16953415
TI  - The role of axial ligands for the structure and function of chlorophylls.
AB  - We have studied the effect of axial ligation of chlorophyll and
      bacteriochlorophyll using density functional calculations. Eleven different axial
      ligands have been considered, including models of histidine, aspartate/glutamate,
      asparagine/glutamine, serine, tyrosine, methionine, water, the protein backbone,
      and phosphate. The native chlorophylls, as well as their cation and anion radical
      states and models of the reaction centres P680 and P700, have been studied and we
      have compared the geometries, binding energies, reduction potentials, and
      absorption spectra. Our results clearly show that the chlorophylls strongly
      prefer to be five-coordinate, in accordance with available crystal structures.
      The axial ligands decrease the reduction potentials, so they cannot explain the
      high potential of P680. They also redshift the Q band, but not enough to explain
      the occurrence of red chlorophylls. However, there is some relation between the
      axial ligands and their location in the various photosynthetic proteins. In
      particular, the intrinsic reduction potential of the second molecule in the
      electron transfer path is always lower than that of the third one, a feature that
      may prevent back-transfer of the electron.

PMID- 16953416
TI  - More pronounced salt dependence and higher reactivity for platination of the
      hairpin r(CGCGUUGUUCGCG) compared with d(CGCGTTGTTCGCG).
AB  - The DNA interference pathways exhibited by cisplatin and related anticancer
      active metal complexes have been extensively studied. Much less is known to what
      extent RNA interaction pathways may operate in parallel, and perhaps contribute
      to both antineoplastic activity and toxicity. The present study was designed with
      the aim of comparing the reactivity of two model systems comprising RNA and DNA
      hairpins, r(CGCGUUGUUCGCG) and d(CGCGTTGTTCGCG), towards a series of platinum(II)
      complexes. Three platinum complexes were used as metallation reagents; cis
      [PtCl(NH3)2(OH2)]+ (1), cis-[PtCl(NH3)(c-C6H11NH2)(OH2)]+ (2), and trans
      [PtCl(NH3)(quinoline)(OH2)]+ (3). The reaction kinetics were studied at pH 6.0,
      25 degrees C, and 1.0 mM < or = I < or = 500 mM. For both types of nucleic acid
      targets, compound 3 was found to react about 1 order of magnitude more rapidly
      than compounds 1 and 2. Further, all platinum compounds exhibited a more
      pronounced salt dependence for the interaction with r(CGCGUUGUUCGCG). Chemical
      and enzymatic cleavage studies revealed similar interaction patterns with
      r(CGCGUUGUUCGCG) after long exposure times to 1 and 2. A substantial decrease of
      cleavage intensity was found at residues G4 and G7, indicative of bifunctional
      adduct formation. Circular dichroism studies showed that platinum adduct
      formation leads to a structural change of the ribonucleic acid. Thermal
      denaturation studies revealed platination to cause a decrease of the RNA melting
      temperatures by 5-10 degrees C. Our observations therefore suggest that RNA is a
      kinetically competitive target to DNA. Furthermore, platination causes
      destabilization of RNA structural elements, which may lead to deleterious
      intracellular effects on biologically relevant RNA targets.

PMID- 16953417
TI  - Inducible immune proteins in the dampwood termite Zootermopsis angusticollis.
AB  - Dampwood termites, Zootermopsis angusticollis (Isoptera: Termopsidae), mount an
      immune response to resist microbial infection. Here we report on results of a
      novel analysis that allowed us to electrophoretically assess changes in hemolymph
      proteins in the same individual before and after exposure to a pathogen. We
      demonstrate that contact with a sublethal concentration of the entomopathogenic
      fungus Metarhizium anisopliae (Deuteromycotina:Hypomycetes) induces the
      production of protective proteins in nymphs, pseudergates (false workers), and
      soldiers. Termites exposed to an immunizing dosage of fungal conidia consistently
      showed an enhancement of constitutive proteins (62-85 kDa) in the hemolymph as
      well as an induction of novel proteins (28-48 kDa) relative to preimmunization
      levels. No significant differences in protein banding patterns relative to
      baseline levels in control and naive termites were observed. Incubating excised
      and eluted induced proteins produced by immunized pseudergates or immunized
      soldiers with conidia significantly reduced the germination of the fungus. The
      fungistatic effect of eluted proteins differed significantly among five colonies
      examined. Our results show that the upregulation of protective proteins in the
      hemolymph underscores the in vivo immune response we previously recorded in Z.
      angusticollis.

PMID- 16953418
TI  - Hyperdisease in the late Pleistocene: validation of an early 20th century
      hypothesis.
AB  - The hypothesis of disease-related large mammal extinction has new support. A
      unique pathologic zone of resorption was first noticed in a Hiscock Mammut
      americanum metacarpal. The pathognomonic zone of resorption was present in fifty
      nine (52%) of 113 skeletons with feet available for examination. Metacarpals and
      metatarsals were most commonly affected. Associated rib periosteal reaction is
      highly suggestive of tuberculosis and the foot lesions were identical to that
      documented in Bison as pathognomonic for tuberculosis. Recognizing that only a
      portion of animals infected by infectious tuberculosis develop bone involvement,
      the high frequency of the pathology in M. americanum suggests that tuberculosis
      was not simply endemic, but actually pandemic, a hyperdisease. Pandemic
      tuberculosis was one of several probable factors contributing to mastodon
      extinction.

PMID- 16953419
TI  - Pm34: a new powdery mildew resistance gene transferred from Aegilops tauschii
      Coss. to common wheat (Triticum aestivum L.).
AB  - Powdery mildew is a major fungal disease in wheat growing areas worldwide. A
      novel source of resistance to wheat powdery mildew present in the germplasm line
      NC97BGTD7 was genetically characterized as a monogenic trait in greenhouse and
      field trials using F(2) derived lines from a NC97BGTD7 X Saluda cross.
      Microsatellite markers were used to map and tag this resistance gene, now
      designated Pm34. Three co-dominant microsatellite markers linked to Pm34 were
      identified and their most likely order was established as: Xbarc177-5D, 5.4cM,
      Pm34, 2.6cM, Xbarc144-5D, 14cM, Xgwm272-5D. These microsatellite markers were
      previously mapped to the long arm of the 5D chromosome and their positions were
      confirmed using Chinese Spring nullitetrasomic Nulli5D-tetra5A and ditelosomic
      Dt5DL lines. Pm2, the only other known Pm gene on chromosome 5D, has been mapped
      to the short arm and its specificity is different from that of Pm34.

PMID- 16953420
TI  - An updated 'Essex' by 'Forrest' linkage map and first composite interval map of
      QTL underlying six soybean traits.
AB  - DNA marker maps based on single populations are the basis for gene, loci and
      genomic analyses. Individual maps can be integrated to produce composite maps
      with higher marker densities if shared marker orders are consistent. However,
      estimates of marker order in composite maps must include sets of markers that
      were not polymorphic in multiple populations. Often some of the pooled markers
      were not codominant, or were not correctly scored. The soybean composite map was
      composed of data from five separate populations based on northern US germplasm
      but does not yet include 'Essex' by 'Forrest' recombinant inbred line (RIL)
      population (E x F) or any southern US soybean cultivars. The objectives were, to
      update the E x F map with codominant markers, to compare marker orders among this
      map, the Forrest physical map and the composite soybean map and to compare QTL
      identified by composite interval maps to the earlier interval maps. Two hundred
      and thirty seven markers were used to construct the core of the E x F map. The
      majority of marker orders were consistent between the maps. However, 19 putative
      marker inversions were detected on 12 of 20 linkage groups (LG). Eleven marker
      distance compressions were also found. The number of inverted markers ranged from
      1 to 2 per LG. Thus, marker order inversions may be common in southern compared
      to northern US germplasm. A total of 61 QTL among 37 measures of six traits were
      detected by composite interval maps, interval maps and single point analysis.
      Seventeen of the QTL found in composite intervals had previously been detected
      among the 29 QTL found in simple interval maps. The genomic locations of the
      known QTL were more closely delimited. A genome sequencing project to compare
      Southern and Northern US soybean cultivars would catalog and delimit inverted
      regions and the associated QTL. Gene introgression in cultivar development
      programs would be accelerated.

PMID- 16953421
TI  - [The serotonin syndrome. Fatal course of intoxication with citalopram and
      moclobemide].
AB  - The serotonin syndrome is caused by a drug-induced increase of the intrasynaptic
      serotonin concentration. Milder forms of the syndrome may be difficult to
      diagnose because of the variability of symptoms. Severe forms often rapidly turn
      into a life-threatening situation, therefore the serotonin syndrome may be a
      challenge for physicians. We describe the pathophysiology and therapeutic options
      of the serotonin syndrome and report about a 42-year-old female patient who
      ingested large amounts of moclobemide, a monoamine oxidase inhibitor, and
      citalopram, a selective serotonin reuptake inhibitor, for attempted suicide.
      Within a few hours the patient developed a lethal serotonin syndrome although ICU
      therapy was initiated immediately.

PMID- 16953422
TI  - [Sleep disturbances in critically ill patients].
AB  - Sleep is an essential part of life with many important roles which include
      immunologic, cognitive and muscular functions. Of the working population 20%
      report sleep disturbances and in critically ill patients an incidence of more
      than 50% has been shown. However, sleep disturbances in the intensive care unit
      (ICU) population have not been investigated in detail. Sleep disturbances in ICU
      patients have a variety of reasons: e.g. patient-related pathologies like sepsis,
      acute or chronic pulmonary diseases, cardiac insufficiency, stroke or epilepsy,
      surgery, therapeutical interventions like mechanical ventilation, noise of
      monitors, pain or medication. Numerous scales and questionnaires are used to
      quantify sleep and the polysomnogramm is used to objectify sleep architecture. To
      improve sleep in ICU patients concepts are needed which include in addition to
      pharmacological treatment (pain reduction and sedation) synchronization of ICU
      activities with daylight, noise reduction and music for relaxation. In order to
      establish evidence-based guidelines, research activities about sleep and critical
      illness should be intensified. Questions to be answered are: 1) Which part of
      sleep disturbances in critically ill patients is directly related to the illness
      or trauma? 2) Is the grade of sleep disturbance correlated with the severity of
      the illness or trauma? 3) Which part is related to the medical treatment and can
      be modified or controlled? In order to define non-pharmacological and
      pharmacological concepts to improve sleep quality, studies need to be randomized
      and to include different ICU populations. The rate of nosocomial infections,
      cognitive function and respiratory muscle function should be considered in these
      studies as well. This will help to answer the question, whether it is useful to
      monitor sleep in ICU patients as a parameter to indicate therapeutical success
      and short-term quality of life. Follow-up needs to be long enough to detect
      adverse effects of withdrawal symptoms after termination of analgesia and
      sedation or delirium.

PMID- 16953423
TI  - Fluctuating awareness of treatment goals among patients and their caregivers: a
      longitudinal study of a dynamic process.
AB  - BACKGROUND: Because increasing numbers of people now survive for months or years
      with advanced cancer, communication between patients, service providers, and
      family caregivers often continues over long periods. Hence, understanding of the
      goals of medical treatment may develop and change as time elapses and disease
      progresses. This understanding is closely related to the "awareness of dying,"
      which has been studied in both qualitative and quantitative research. However,
      when both a patient and family caregiver are involved, the question of
      "awareness" becomes more complex. A recent longitudinal study reported on patient
      and caregiver knowledge of treatment goals, but no comparison of such knowledge
      using matched interview schedules and paired data analysis has been provided.
      This report examines patterns of awareness and factors associated with these
      patterns. MATERIALS AND METHODS: One hundred sixty-three patients with incurable
      cancer and their nominated principal family caregivers (136) were recruited from
      The Canberra Hospital Oncology Services. Participants' understanding of the
      treatment goals were measured by interview questions at weeks 1 and 12. RESULTS:
      One-third of both patients and caregivers understood that the treatment goal was
      not curative; however, not all patient and caregiver pairs had the same
      understanding. In 15% of pairs, both patient and caregiver believed that the goal
      of treatment was curative, while another 13% said that they did not know the aim
      of the treatment. Thirty-nine percent of pairs registered incongruent responses
      in which only one member of the pair understood that the treatment was not
      intended to cure the disease. Over time, a few respondents changed their
      perception of the treatment goals toward accurate clarification. Bivariate
      analysis using an awareness variable, constructed for the purpose, showed that in
      6 months before death, at least one person in 89% of pairs understood that the
      treatment was noncurative. Time-to-death, gender, and place of residence were
      also important predictors of knowledge. CONCLUSIONS: Discrepancies between
      patients and their caregivers may complicate the delivery of effective care when
      patients are seriously ill. Misunderstanding or uncertainty about treatment goals
      will obstruct proper informed consent. Health professionals providing care for
      families dealing with advanced cancer must recognize that the discussion of
      treatment goals is a dynamic process, which may require them to extend their
      communication skills.

PMID- 16953425
TI  - Automated fast perfusion of Xenopus oocytes for drug screening.
AB  - Fast ('concentration jump') applications of neurotransmitters are crucial for
      screening studies on ligand-gated ion channels. In this paper, we describe a
      method for automated fast perfusion of neurotransmitters (or drugs) during two
      microelectrode voltage-clamp experiments on Xenopus oocytes. The oocytes are
      placed in a small bath chamber that is covered by a glass plate with two channels
      for the microelectrodes that are surrounded by a quartz funnel serving as a
      reservoir for test solutions. The oocytes are perfused in a vertical direction
      via the two channels in the plate. Automation of compound delivery is
      accomplished by means of a programmable pipetting workstation. A mean rise time
      for 10-90% current increase through muscle-type nACh channels of 55.0+/-1.3 ms
      (30 muM acetylcholine) was estimated. Automation, fast perfusion rates, and
      economical use of compounds ( approximately 100 mul/data point) make the system
      suitable for screening studies on ligand- and voltage-gated ion channels.

PMID- 16953424
TI  - Rho-kinase-mediated regulation of receptor-agonist-stimulated smooth muscle
      contraction.
AB  - Rho kinase was shown to regulate smooth muscle contraction through modulating
      myosin phosphatase (MLCP) activity, but the in vivo mechanism remains to be
      clarified. This study examined the effects of Rho kinase inhibition on the
      phosphorylation time course of MLCP subunit MYPT1 at Thr697 and Thr855 and MLCP
      inhibitory protein CPI-17 at Thr38 and on actin polymerization during the
      contraction of rat tail artery (RTA) smooth muscle. Rho kinase inhibitor Y27632
      suppressed force activated by alpha(1)-adrenergic agonist phenylephrine or
      thromboxane A(2) analog U46619 with concomitant decreases in MLC(20)
      phosphorylation. Phenylephrine and U46619 significantly increased MYPT1(Thr855)
      phosphorylation that was eliminated by Y27632 pretreatment, whereas MYPT1(Thr697)
      phosphorylation was not stimulated. Phenylephrine increased CPI-17(Thr38)
      phosphorylation that was not inhibited by Y27632 but was abolished by a protein
      kinase C inhibitor Ro 31-8220; in contrast, U46619 did not stimulate CPI-17
      phosphorylation. Both agonists increased actin polymerization that was diminished
      by Y27632 under phenylephrine but not U46619 activation. These results
      demonstrated a temporal correlation between MYPT1(Thr855) phosphorylation,
      MLC(20) phosphorylation, and contraction in a Rho-kinase-dependent manner for
      both phenylephrine and U46619 stimulation, suggesting that Rho kinase regulates
      MLCP activity through MYPT1(Thr855) phosphorylation during RTA smooth muscle
      contraction. Furthermore, Rho kinase regulates actin polymerization activated by
      alpha(1)-adrenoceptors but is less significant in thromboxane receptor
      stimulation.

PMID- 16953427
TI  - The only effects of recombinant follicle-stimulating hormone for ovulation
      induction in the pre-implantation period of rats.
AB  - OBJECTIVE: The aim of this study was to evaluate the changes in follicular
      development, serum hormonal levels, and endometrium in the pre-implantation
      period of rats by using recombinant FSH (rFSH) without human chorionic
      gonadotropin (hCG). METHODS: Thirty female rats were studied in six groups of
      five specimens. Two groups determined as controls (groups 1 and 2). Two groups
      received constant doses of rFSH (groups 3 and 4) and other two decreasing doses
      (groups 5 and 6). One of the paired groups was mated. Uterus, ovaries, and blood
      samples were taken from non-mated groups (groups 1, 3, and 5) at the proestrus
      period and from mated groups (groups 2, 4, and 6) in the pre-implantation period.
      RESULTS: In non-mated groups antral follicles and corpus luteum periodicum and in
      mated groups antral follicles, corpus luteum periodicum, and corpus luteum
      graviditatis were increased in rFSH groups, especially in decreasing dose groups.
      Estradiol (E2) levels were increased and progesterone (P)/E2 ratio was
      significantly decreased in decreasing dose groups. Endometrium surface epithelium
      was columnar, irregular, and folded in rFSH groups. Endometrium glandular
      epithelium was cuboidal in all groups. In decreasing dose groups endometrial
      stroma was smooth and fibroblastic. Mitotic indices of endometrium surface,
      glandular epithelium, and stroma were significantly decreased in rFSH groups.
      Primary follicles and P levels showed no change. CONCLUSION: It seems likely that
      decreasing doses of rFSH might be used in order to improve follicular
      development, although it has negative effects with E2 on endometrium in the pre
      implantation period of rats.

PMID- 16953426
TI  - Analysis of candidate genes on chromosome 2 in oral cleft case-parent trios from
      three populations.
AB  - Isolated oral clefts, including cleft lip with/without cleft palate (CL/P) and
      cleft palate (CP), have a complex and heterogeneous etiology. Case-parent trios
      from three populations were used to study genes spanning chromosome 2, where
      single nucleotide polymorphic (SNP) markers were analyzed individually and as
      haplotypes. Case-parent trios from three populations (74 from Maryland, 64 from
      Singapore and 95 from Taiwan) were genotyped for 962 SNPs in 104 genes on
      chromosome 2, including two well-recognized candidate genes: TGFA and SATB2.
      Individual SNPs and haplotypes (in sliding windows of 2-5 SNPs) were used to test
      for linkage and disequilibrium separately in CL/P and CP trios. A novel candidate
      gene (ZNF533) showed consistent evidence of linkage and disequilibrium in all
      three populations for both CL/P and CP. SNPs in key regions of ZNF533 showed
      considerable variability in estimated genotypic odds ratios and their
      significance, suggesting allelic heterogeneity. Haplotype frequencies for regions
      of ZNF533 were estimated and used to partition genetic variance into among-and
      within-population components. Wright's fixation index, a measure of genetic
      diversity, showed little difference between Singapore and Taiwan compared with
      Maryland. The tensin-1 gene (TNS1) also showed evidence of linkage and
      disequilibrium among both CL/P and CP trios in all three populations, albeit at a
      lower level of significance. Additional genes (VAX2, GLI2, ZHFX1B on 2p; WNT6
      WNT10A and COL4A3-COL4A4 on 2q) showed consistent evidence of linkage and
      disequilibrium only among CL/P trios in all three populations, and TGFA showed
      significant evidence in two of three populations.

PMID- 16953428
TI  - Biochemical and cellular characterization of the plant ortholog of PYM, a protein
      that interacts with the exon junction complex core proteins Mago and Y14.
AB  - The exon junction complex (EJC) plays an important role in post-transcriptional
      control of gene expression. Mago nashi (Mago) and Y14 are core EJC proteins that
      operate as a functional unit in animal cells, and the Mago-Y14 heterodimer
      interacts with other EJC core and peripheral proteins. Little is known about the
      biochemical and cellular characteristics of the EJC and its orthologs in plants.
      Here, we demonstrate that Arabidopsis Mago and Y14 form a ternary complex with
      PYM, an RNA-binding protein that was previously shown to interact with the Mago
      Y14 heterodimer in Drosophila. Fluorescence microscopy indicated that Arabidopsis
      Mago and Y14 are localized primarily in the nucleus, whereas PYM is mostly
      cytoplasmic. In vitro pull-down assays using recombinant proteins showed that the
      amino-terminal region of the Arabidopsis PYM interacts with the Mago-Y14
      heterodimer, a similar observation to that previously reported for the animal
      versions of these proteins. However, we demonstrated also that Arabidopsis PYM
      has the ability to interact with monomeric Mago and monomeric Y14.
      Immunoprecipitation and tandem affinity purification from whole cell extracts
      detected a subtle interaction between the Arabidopsis Mago-Y14 heterodimer and
      PYM in flowers, indicating that the ternary complex is not abundant in plant
      cells. The regions of the polypeptide responsible for nuclear import and export
      were defined using protein truncations and site-directed mutagenesis. This study
      identifies unique characteristics of Arabidopsis Mago, Y14 and PYM compared to
      those observed in animal cells. These are predicted to have important functional
      implications associated with post-transcriptional regulation of gene expression
      in plant cells.

PMID- 16953429
TI  - Major differences observed in transcript profiles of blueberry during cold
      acclimation under field and cold room conditions.
AB  - Our laboratory has been working toward increasing our understanding of the
      genetic control of cold hardiness in blueberry (Vaccinium section Cyanococcus) to
      ultimately use this information to develop more cold hardy cultivars for the
      industry. Here, we report using cDNA microarrays to monitor changes in gene
      expression at multiple times during cold acclimation under field and cold room
      conditions. Microarrays contained over 2,500 cDNA inserts, approximately half of
      which had been picked and single-pass sequenced from each of two cDNA libraries
      that were constructed from cold acclimated floral buds and non-acclimated floral
      buds of the fairly cold hardy cv. Bluecrop (Vaccinium corymbosum L.). Two
      biological samples were examined at each time point. Microarray data were
      analyzed statistically using t tests, ANOVA, clustering algorithms, and online
      analytical processing (OLAP). Interestingly, more transcripts were found to be
      upregulated under cold room conditions than under field conditions. Many of the
      genes induced only under cold room conditions could be divided into three major
      types: (1) genes associated with stress tolerance; (2) those that encode
      glycolytic and TCA cycle enzymes, and (3) those associated with protein synthesis
      machinery. A few of the genes induced only under field conditions appear to be
      related to light stress. Possible explanations for these differences are
      discussed in physiological context. Although many similarities exist in how
      plants respond during cold acclimation in the cold room and in the field
      environment, there are major differences suggesting caution should be taken in
      interpreting results based only on artificial, cold room conditions.

PMID- 16953430
TI  - Cytological diploidization and rapid genome changes of the newly synthesized
      allotetraploids Cucumis x hytivus.
AB  - We used a newly synthesized allotetraploid between C. sativus (2n = 2x = 14, n
      gametic chromosome number, x haploid chromosome number) and C. hystrix (2n = 2x =
      24) to study the genomic events in its early generations. Results from
      cytological characterization of the F(1) and the allotetraploid progenies showed
      that the rate of bivalents in meiotic metaphase I of the F(1) was greatly
      improved by chromosome doubling, and further improved during the selfing process
      of allopolyploid resulting into relatively diploid-like meiosis. Extensive
      genomic changes were detected by amplified fragment length polymorphism analysis.
      The changes mainly involved loss of parental restriction fragments and gaining of
      novel fragments. The total detectable changes were from 11.1 to 32.1%, and the
      frequency of losing parental fragments was much higher than that of gaining novel
      fragments. Some of the changes were initiated as early as in the F(1) hybrid,
      whereas others occurred after chromosome doubling (polyploid formation). No
      significant differences were detected in the reciprocal F(1) hybrids and S(0)
      generations. But the data showed that the frequency of sequence losing in C.
      sativus was about two times higher than in the C. hystrix. Our results
      demonstrated that the sequence elimination was the major event of genomic
      changes, and it might provide the physical basis for the diploid-like meiotic
      behavior in the diploidization of the newly formed allopolyploids. Moreover, the
      results suggest that the sequence elimination was not caused by cytoplasmic
      factors, and might relate to genomic recombination and to the numbers of parental
      chromosome.

PMID- 16953431
TI  - Genetic engineering of the biosynthesis of glycinebetaine enhances
      thermotolerance of photosystem II in tobacco plants.
AB  - Genetically engineered tobacco (Nicotiana tabacum L.) with the ability to
      accumulate glycinebetaine was established. The wild type and transgenic plants
      were exposed to heat treatment (25-50 degrees C) for 4 h in the dark and under
      growth light intensity (300 mumol m(-2) s(-1)). The analyses of oxygen-evolving
      activity and chlorophyll fluorescence demonstrated that photosystem II (PSII) in
      transgenic plants showed higher thermotolerance than in wild type plants in
      particular when heat stress was performed in the light, suggesting that the
      accumulation of glycinebetaine leads to increased tolerance to heat-enhanced
      photoinhibition. This increased tolerance was associated with an improvement on
      thermostability of the oxygen-evolving complex and the reaction center of PSII.
      The enhanced tolerance was caused by acceleration of the repair of PSII from heat
      enhanced photoinhibition. Under heat stress, there was a significant accumulation
      of H(2)O(2), O (2) (-) and catalytic Fe in wild type plants but this accumulation
      was much less in transgenic plants. Heat stress significantly decreased the
      activities of catalase, ascorbate peroxidase, glutathione reductase,
      dehydroascorbate reductase, and monodehydroascorbate reductase in wild type
      plants whereas the activities of these enzymes either decreased much less or
      maintained or even increased in transgenic plants. In addition, heat stress
      increased the activity of superoxide dismutase in wild type plants but this
      increase was much greater in transgenic plants. Furthermore, transgenic plants
      also showed higher content of ascorbate and reduced glutathione than that of wild
      type plants under heat stress. The results suggest that the increased
      thermotolerance induced by accumulation of glycinebetaine in vivo was associated
      with the enhancement of the repair of PSII from heat-enhanced photo inhibition,
      which might be due to less accumulation of reactive oxygen species in transgenic
      plants.

PMID- 16953432
TI  - APETALA2 like genes from Picea abies show functional similarities to their
      Arabidopsis homologues.
AB  - In angiosperm flower development the identity of the floral organs is determined
      by the A, B and C factors. Here we present the characterisation of three
      homologues of the A class gene APETALA2 (AP2) from the conifer Picea abies
      (Norway spruce), Picea abies APETALA2 LIKE1 (PaAP2L1), PaAP2L2 and PaAP2L3.
      Similar to AP2 these genes contain sequence motifs complementary to miRNA172 that
      has been shown to regulate AP2 in Arabidopsis. The genes display distinct
      expression patterns during plant development; in the female-cone bud PaAP2L1 and
      PaAP2L3 are expressed in the seed-bearing ovuliferous scale in a pattern
      complementary to each other, and overlapping with the expression of the C class
      related gene DAL2. To study the function of PaAP2L1 and PaAP2L2 the genes were
      expressed in Arabidopsis. The transgenic PaAP2L2 plants were stunted and flowered
      later than control plants. Flowers were indeterminate and produced an excess of
      floral organs most severely in the two inner whorls, associated with an ectopic
      expression of the meristem-regulating gene WUSCHEL. No homeotic changes in floral
      organ identities occurred, but in the ap2-1 mutant background PaAP2L2 was able to
      promote petal identity, indicating that the spruce AP2 gene has the capacity to
      substitute for an A class gene in Arabidopsis. In spite of the long evolutionary
      distance between angiosperms and gymnosperms and the fact that gymnosperms lack
      structures homologous to sepals and petals our data supports a functional
      conservation of AP2 genes among the seed plants.

PMID- 16953433
TI  - Structural and enzymatic characterization of the isoamylase1 homo-oligomer and
      the isoamylase1-isoamylase2 hetero-oligomer from rice endosperm.
AB  - The present study established that there are two distinct polymeric forms of
      isoamylase1 (ISA1) in rice endosperm: presumably a homo-pentamer of ISA1 and a
      hetero-hexamer composed of five ISA1 and one ISA2. The molecular sizes of the
      homo- and hetero-oligomers, which could be fractionated by hydrophobic
      chromatography, were approximately 420-480 and 510-550 kDa, respectively. The
      hetero-oligomer exhibited higher affinities for various branched polyglucans,
      especially for phytoglycogen, which had a K(m) value that was approximately 12
      times lower relative to that with the homo-oligomer, although no marked
      differences were found in chain preferences for debranching of amylopectin and
      phytoglycogen between these forms. The hetero-oligomer was active even when
      incubated at 50 degrees C for 10 min, while the homo-multimer was completely
      inactivated at 40 degrees C in 10 min. When the ISA1 homo-oligomer was incubated
      with the ISA2 protein expressed in Escherichia coli and applied onto a
      nondenature polyacrylamide gel, additional debranching activity bands which were
      specific for the purified ISA1-ISA2 preparation were also detected, indicating
      that ISA1 and ISA2 combine to form a hetero-oligomer. These results suggest that
      the hetero-oligomer plays a predominant role in the amylopectin biosynthesis in
      rice endosperm although the homo-oligomer can complement the function of the
      hetero-oligomer at least to some extent.

PMID- 16953434
TI  - The role of body-based sensory information in the acquisition of enduring spatial
      representations.
AB  - Although many previous studies have shown that body-based sensory modalities such
      as vestibular, kinesthetic, and efferent information are useful for acquiring
      spatial information about one's immediate environment, relatively little work has
      examined how these modalities affect the acquisition of long-term spatial memory.
      Three groups of participants learned locations along a 146 m indoor route, and
      subsequently pointed to these locations, estimated distances between them, and
      constructed maps of the environment. One group had access to visual,
      proprioceptive, and inertial information, another had access to matched visual
      and matched inertial information, and another had access only to matched visual
      information. In contrast to previous findings examining transient, online spatial
      representations, our results showed very few differences among groups in the
      accuracy of the spatial memories acquired. The only difference was the improved
      pointing accuracy of participants who had access to proprioceptive information
      relative to that of participants in the other conditions. Results are discussed
      in terms of differential sensory contributions to transient and enduring spatial
      representations.

PMID- 16953435
TI  - Human non-visual discrimination of gradual turning is poor.
AB  - We report three measures of the ability of normally sighted adults to
      discriminate turning while walking blindfolded outdoors. Constant error in
      selecting line drawings of paths indicated that participants under represent the
      amount of turning along more curved paths and over represent the amount of
      turning on less curved paths. Constant error in the direction of pointing to the
      origin of paths indicated a bias consistent with the direction of turning along
      more curved paths. Participants produced more accurate drawings of paths as the
      amount of turning increased. The results suggest that non-visual cues that
      accompany self movement are not sufficient for accurate representation of large
      radius curves in geographic scale travel.

PMID- 16953436
TI  - Vaccination against prostate cancer using a live tissue factor deficient cell
      line in Lobund-Wistar rats.
AB  - Reducing expression of the tissue factor gene in prostate adenocarcinoma cells
      (PAIII) results in a cell line that, in vivo, mimics the growth of wildtype (wt)
      PAIII. However, instead of continuing to grow and metastasize as wt PAIII tumors
      do, tissue factor deficient PAIII (TFD PAIII) masses spontaneously regress after
      several weeks. Although whole cell vaccines are typically inactivated prior to
      administration to prevent proliferation within the host, numerous studies have
      suggested that exposure to live, attenuated, whole tumor cells, and the
      extracellular microenvironment they recruit, increases immunotherapeutic
      potential. Here, we provide support for this notion, and a strategy through which
      to implement it, by demonstrating that subcutaneous vaccinations with the TFD
      PAIII protect the Lobund-Wistar rat against subsequent wt PAIII cell challenge.
      TFD PAIII immunized rats suffered significantly less metastasis of wt PAIII
      challenge tumors compared to unvaccinated naive controls rats. These results
      offer the intriguing possibility that the TFD PAIII vaccine is an effective
      system for the prevention and, possibly, the treatment of prostate cancer.

PMID- 16953437
TI  - [Regenerative therapy in cardiology: how distant is it from reality?].
AB  - During acute myocardial infarction, ischemia causes progressive loss of
      contractile tissue. Subsequently, structural changes lead to left ventricular
      remodeling finally resulting in the development of heart failure. In addition to
      an optimal reperfusion and pharmacologinal post-infarction therapy, increased
      neovascularization and regeneration of cardiomyocytes could reduce or even
      abolish the ongoing left ventricular remodeling processes within the infarct
      area. Experimental studies have demonstrated that transplantation of adult
      progenitor cells leads to increased neovascularization, reduced fibrosis and,
      therefore, increased left ventricular function after acute myocardial infarction.
      In contrast to current treatment strategies, progenitor cell therapy offers a new
      regenerative approach for myocardial tissue. Initial clinical studies have
      demonstrated, apart from safety and feasibility of intracoronary infusion of
      adult autologous progenitor cells, a significant improvement of left ventricular
      function, geometry and vascularization in patients with acute myocardial
      infarction receiving intracoronary infusion of progenitor cells. However, in
      patients with chronic ischemic cardiomyopathy, the improvement in contractility
      is less pronounced. Finally, whether intracoronary infusion of adult progenitor
      cells can also reduce morbidity and mortality due to heart failure, remains to be
      investigated.

PMID- 16953438
TI  - [A 32-year-old patient with diarrhoea and acute kidney failure].
AB  - A 32-year-old male patient presented in the emergency department of our hospital
      with acute vomiting and diarrhoea. He reported occasional non-severe diarrhoea
      over several years in the past. Furthermore, at the time of presentation the
      patient had had anuria for several days. A prerenal and postrenal origin of the
      renal failure was excluded. A renal biopsy was performed and histopathological
      examination displayed findings consistent with a haemolytic-uraemic syndrome but
      no signs of glomerulonephritis. MRI examination of the small bowel revealed
      inflammatory alterations typical for Crohn's disease, even without histological
      verification. We describe haemolytic-waemic syndrome as manifestation of Crohn's
      disease for the first time.

PMID- 16953439
TI  - Molecular and cellular basis for pathogenicity of autoantibodies: lessons from
      murine monoclonal autoantibodies.
AB  - The pathogenesis of autoantibody-mediated cellular and tissue lesions in
      autoimmune diseases is most straightforwardly attributable to the combined action
      of self-antigen binding properties and effector functions associated with the Fc
      regions of the different immunoglobulin (Ig) isotypes. The analysis of two
      different sets of monoclonal autoantibodies derived from lupus-prone mice
      revealed remarkable differences in the pathogenic potentials of different IgG
      subclasses: (1) the IgG2a and IgG2b subclasses of anti-red blood cell (RBC)
      autoantibodies are the most pathogenic and efficiently activate two classes of
      activating IgG Fc receptors (FcgammaRIII and FcgammaRIV) and complement; (2) the
      IgG3 subclass is less pathogenic and activate only complement; and (3) the IgG1
      subclass is the least pathogenic and interact only with FcgammaRIII. In addition,
      because of the unique property of IgG3 to form self-associating complexes and
      generate cryoglobulins, this subclass of rheumatoid factor and anti-DNA
      autoantibodies became highly pathogenic and induced lupus-like nephritis and/or
      vasculitis. Since the switch to IgG2a and IgG3 is promoted by Th1 cytokine
      interferon gamma, these results strongly suggest that Th1 autoimmune responses
      could be critically involved in the generation of more pathogenic autoantibodies
      in systemic lupus erythematosus. This finding is consistent with the observation
      that the progression of murine lupus nephritis is correlated with the relative
      dominance of Th1 autoimmune responses. Finally, the analysis of IgG glycosylation
      pattern revealed that more sialylated IgG autoantibodies remained poorly
      pathogenic because of limited Fc-associated effector functions and loss of
      cryoglobulin activity. This suggests that the terminal sialylation of the
      oligosaccharide side chains of IgG could be a significant factor determining the
      pathogenic potential of autoantibodies. Our results thus underline the importance
      of subpopulations of autoantibodies, induced by the help of Th1 cells, in the
      pathogenesis of autoantibody-mediated cellular and tissue injuries.

PMID- 16953441
TI  - Localized and delocalized perfluorosemibullvalenes.
AB  - On the basis of the experimental Gibbs free-energy barrier of the degenerate Cope
      arrangement in semibullvalene, B3P86 shows the best agreement, while B3LYP and
      MP2 underestimate and CCSD(T) overestimates the barrier. The substituent effect
      proposal by Hoffmann has been verified. In contrast to semibullvalenes with
      either localized energy-minimum structures or delocalized transition-state
      structures, perfluorosemibullvalene has both localized and delocalized energy
      minimum structures that are very close in energy.

PMID- 16953440
TI  - TCRzeta mRNA splice variant forms observed in the peripheral blood T cells from
      systemic lupus erythematosus patients.
AB  - Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown
      etiology. Tyrosine phosphorylation and protein expression of the T-cell receptor
      zeta chain (zeta) have been reported to be significantly decreased in SLE T
      cells. In addition, zeta mRNA with alternatively spliced 3' untranslated region
      (zetamRNA/as-3'UTR) is detected predominantly in SLE T cells, and aberrant zeta
      mRNA accompanied by the mutations in the open reading frame including zeta mRNA
      lacking exon7 (zetamRNA/exon7-) is observed in SLE T cells. These zeta mRNA
      splice variant forms exhibit a reduction in the expression of TCR/CD3 complex and
      zeta protein on their cell surface due to the instability of zeta mRNA splice
      variant forms as well as the reduction in interleukin (IL)-2 production after
      stimulating with anti-CD3 antibody. Data from cDNA microarray showed that 36
      genes encoding cytokines and chemokines, including IL-2, IL-15, IL-18, and TGF
      beta2, were down-regulated in the MA5.8 cells transfected with the zeta mRNA
      splice variant forms. Another 16 genes were up-regulated and included genes
      associated with membranous proteins and cell damage granules, including the genes
      encoding poliovirus-receptor-related 2, syndecan-1, and granzyme A.

PMID- 16953442
TI  - Structure-based 3D-QSAR studies on thiazoles as 5-HT3 receptor antagonists.
AB  - Structure-based 3D-QSAR studies were performed on 20 thiazoles against their
      binding affinities to the 5-HT(3) receptor with comparative molecular field
      analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA).
      The thiazoles were initially docked into the binding pocket of a human 5-HT(3A)
      receptor homology model, constructed on the basis of the crystal structure of the
      snail acetylcholine binding protein (AChBP), using the GOLD program. The docked
      conformations were then extracted and used to build the 3D-QSAR models, with
      cross-validated r2omega values 0.785 and 0.744 for CoMFA and CoMSIA,
      respectively. An additional five molecules were used to validate the models
      further, giving satisfactory predictive r2 values of 0.582 and 0.804 for CoMFA
      and CoMSIA, respectively. The results would be helpful for the discovery of new
      potent and selective 5-HT(3) receptor antagonists.

PMID- 16953443
TI  - Solving the chemical master equation for monomolecular reaction systems
      analytically.
AB  - The stochastic dynamics of a well-stirred mixture of molecular species
      interacting through different biochemical reactions can be accurately modelled by
      the chemical master equation (CME). Research in the biology and scientific
      computing community has concentrated mostly on the development of numerical
      techniques to approximate the solution of the CME via many realizations of the
      associated Markov jump process. The domain of exact and/or efficient methods for
      directly solving the CME is still widely open, which is due to its large
      dimension that grows exponentially with the number of molecular species involved.
      In this article, we present an exact solution formula of the CME for arbitrary
      initial conditions in the case where the underlying system is governed by
      monomolecular reactions. The solution can be expressed in terms of the
      convolution of multinomial and product Poisson distributions with time-dependent
      parameters evolving according to the traditional reaction-rate equations. This
      very structured representation allows to deduce easily many properties of the
      solution. The model class includes many interesting examples. For more complex
      reaction systems, our results can be seen as a first step towards the
      construction of new numerical integrators, because solutions to the monomolecular
      case provide promising ansatz functions for Galerkin-type methods.

PMID- 16953444
TI  - Immunocompetence does not correlate with resistance to helminth parasites in
      house mouse subspecies and their hybrids.
AB  - A central point not yet elucidated in immuno-ecological studies is whether the
      different ways to assess the immune status of individuals are good indicators of
      parasite resistance of the host. We investigate the relationship between
      immunocompetence and the resistance/susceptibility phenotype of five strains of
      two European subspecies of the house mouse and their hybrids derived from natural
      populations. The assessment of immunocompetence was measured indirectly by the
      mass of the spleen and directly by the phytohaemagglutinin (PHA) test. The
      resistance of each mouse strain to common helminths was previously determined by
      the distribution of parasite burdens obtained after experimental infection. We
      found no relationship between the resistance/susceptibility phenotype of strains
      and the level of PHA response or the size of the spleen. A significant negative
      correlation was found between residuals of log spleen mass (controlled for body
      mass) and PHA response, suggesting that these two components of immune function
      are not independent measures of defence against parasitism. We discuss the
      validity of these two techniques of measuring immunocompetence and emphasize the
      importance of taking into account the complexity of the immune system at
      structural and functional levels in understanding the component of selection
      attributable to parasitism in the evolution of immunocompetence.

PMID- 16953445
TI  - Body composition and nutritional intake in children with chronic kidney disease.
AB  - The aim of this study was to assess body composition in children with chronic
      renal failure (CRF) and post renal transplantation (Tx), and to compare it to
      body mass index (BMI) and nutritional intake. Dietary assessment using 3-day
      diaries, total and regional body composition assessment by dual x-ray energy
      absorptiometry of 50 CRF children (29M, 21F), median age 8.9 yrs and 50 Tx
      children (32M, 18F), median age 12.9 yrs. BMI, percentage fat mass (%FM) and lean
      mass (LM) were corrected for height and expressed as SDS (HSDS). In both groups,
      BMIHSDS was lower than %FMHSDS and higher than LMHSDS (p<0.05). In the Tx group,
      there were associations on bivariate analysis between energy & protein intake and
      BMIHSDS & %FMHSDS (r,0.5, p<0.05), and between LMHSDS and protein intake (r,0.5,
      p<0.05). On multivariate analysis, there was an association between LMHSDS and
      time since transplantation (r,-0.4, p<0.05). Children in the CRF and Tx groups
      had a high percentage predicted trunk:leg FM ratio of 148% and 157%,
      respectively. Children with CRF and Tx have discordant body composition with a
      relatively high FM and low LM, which is not reflected by BMI. In addition, they
      appear to have an increased level of central adiposity that may predispose them
      to increased morbidity in later life.

PMID- 16953446
TI  - Low-dose aspirin before spinal surgery: results of a survey among neurosurgeons
      in Germany.
AB  - The main problem faced by the increasing numbers of patients presenting for
      spinal surgery are receiving concurrent medication with low-dose aspirin, leading
      to dysfunctional circulating platelets. The contribution of low-dose aspirin to
      increased peri-operative risk of bleeding and blood loss is a contentious issue
      with conflicting published results from different surgical groups. Data from
      neurosurgical spine patients is sparse, but aspirin has been identified as an
      important risk factor in the development of post-operative hematoma following
      intracranial surgery. We surveyed the opinions and working practices of the
      neurosurgical facilities performing spinal operations in Germany regarding
      patients who present for elective spinal surgery. Identical questionnaires were
      sent to 210 neurosurgical facilities and proffered five main questions: (1) the
      adherence of any policy of stopping aspirin pre-operatively, (2) the personal
      risk assessment for patients with spinal surgery under low-dose aspirin
      medication, (3) the preferred method of treatment for excessive bleeding in this
      context, (4) personal knowledge of hemorrhagic complications in this group of
      patients, and (5) the characteristics of the neurosurgical units concerned. There
      were 145 (69.1%) responses of which 142 (67.6%) were valid. Of the respondents,
      114 (80.3%) had a (written) departmental policy for the discontinuation of pre
      operative aspirin treatment, 28 (19.7%) were unaware of such a policy. The mean
      time suggested for discontinuation of aspirin pre-operatively was 6.9 days
      (range: 0-21 days), with seven respondents who perform the operations despite the
      ongoing aspirin medication. Ninety-four respondents (66.2%) considered that
      patients taking low-dose aspirin were at increased risk for excessive peri
      operative hemorrhage or were indetermined (8.6%), and 73 (51.4%) reported having
      personal experience of such problems. Ninety-two respondents (65.5%) would use
      special medical therapy, preferably Desmopressin alone or in combination with
      other blood products or prohemostatic agents (46.1%), if hemorrhagic
      complications developed intra- or post-operatively. The average number of spinal
      operations per year in each service was 607.9 (range: 40-1,500). Despite the
      existence of distinct departmental policies concerning the discontinuation of low
      dose aspirin pre-operatively in the majority of neurosurgical facilities
      performing spinal operations, there is a wide range of the moment of this
      interruption with an average of 7 days. Two-thirds of the respondents felt that
      aspirin was a risk factor for hemorrhagic complications associated with spinal
      procedures, and more than half of the interviewees reported having personal
      experience of such problems. Finally, various medicamentous methods of
      counteracting aspirin-induced platelet dysfunction and excessive bleeding in this
      context are elicited, discussed and evaluated.

PMID- 16953447
TI  - Comparative multifactorial analysis of the effects of idiopathic adolescent
      scoliosis and Scheuermann kyphosis on the self-perceived health status of
      adolescents treated with brace.
AB  - Bracing is the most effective non-operative treatment for mild progressive spinal
      deformities in adolescence but it has shown a considerable impact on several
      aspects of adolescents' functioning. This cross-sectional study investigated the
      self-perceived health status of adolescents with the two most common deformities,
      treated with body orthosis. Seventy-nine adolescents with spinal deformities
      (idiopathic adolescent scoliosis, thoracic Scheuermann kyphosis) and 62
      adolescents without spinal deformities were asked to complete the Quality of Life
      profile for Spine Deformities Instrument. This study showed that adolescents with
      deformities are significantly less likely to have back pain in training than
      controls, but more likely to have difficulty in forward bending, and in the most
      common daily activities while in brace. These individuals claim they wake up
      because of back pain and feel quite nervous with the external appearance of their
      body. These patients face often problems with their relations with friends, while
      they reported difficulties in getting up from bed and sleep at night more often
      than their counterparts without deformities. As they grow older, patients feel
      increasing ashamed of their body, as they are more concerned about the future
      effect of the deformity on their body. As the bracing time increases, patients
      have much more probability than controls to get low back pain. Girls with
      deformity have a higher probability than boys to get low back pain while working
      in the house and while training. Individuals with larger spinal curvatures have
      more difficulties in bending and increased incidence of back pain than their
      counterparts with smaller curvatures. Psychological reasons associated mainly
      with relations at school and back pain are the main causes for low compliance in
      adolescents with spinal deformities treated with body orthosis. Careful
      instructions for all individuals who will undergo brace therapy, psychological
      support for all patients who develop psychological reactions and physical
      training particularly for older girls should be recommended to increase bracing
      compliance.

PMID- 16953448
TI  - MRI diagnosis of hypertrophic osteoarthropathy from a remote childhood
      malignancy.
AB  - Hypertrophic osteoarthropathy (HOA) is a clinico-radiological syndrome
      characterized by digital clubbing, periosteal proliferation, bone pain, synovitis
      and arthralgia, all of these being commonly symmetrical. It is occasionally
      associated with nasopharyngeal lymphoepitheliomas and may develop before or after
      development of lung metastases in these patients. We report a case of a healthy
      22-year-old female who presented to our institution with pain and swelling in the
      thighs and legs. She had a history of childhood nasopharyngeal lymphoepithelioma.
      Radiographs of the knees were negative. Magnetic resonance imaging (MRI) showed
      features suggestive of bilateral periostitis. Because of the propensity of the
      rare childhood nasopharyngeal lymphoepithelioma to present with HOA, this entity
      was included in the differential diagnosis. A subsequent chest radiograph and CT
      demonstrated a lung and mediastinal mass that were histologically confirmed to be
      metastatic. To the best of our knowledge, HOA and metastases from nasopharyngeal
      lymphoepithelioma occurring after such a long time interval have not been
      previously reported. Early demonstration and consideration of HOA on the basis of
      MRI, lead to expeditious and appropriate subsequent investigation.

PMID- 16953450
TI  - Clinical and radiological features related to the growth potential of meningioma.
AB  - Clinical and radiological features that help predict the growth potential of
      meningioma would be beneficial. The purpose of this study is to clarify the
      characteristics related to proliferating potential using the MIB-1 staining
      index. We analyzed the relationship of MIB-1 staining indices to characteristics
      of 342 consecutive patients with meningioma surgically removed between 1995 and
      2004 by logistic regression analysis. One hundred and forty-nine of the patients
      with meningioma were >or=60 in age; 89 male; 48 recurrent; 203 symptomatic; 157
      at the skull base; 124 over 20 cm(3); 24 multiple; 136 with edema; 117 with
      calcification. The MIB-1 staining index in 56 of 296 grade I meningiomas in WHO
      classification was >or= 3.0; in 27 of 28 grade II; and in 17 of 18 grade III,
      respectively. Logistic regression analysis demonstrated that male (odds ratio
      [OR], 2.374, p=0.003), recurrence (OR, 7.574, p=0.0001), skull base (OR, 0.540,
      p=0.035), calcification (OR, 0.498, p=0.019) were independent risk factors for a
      high MIB-1 staining index (>or=3.0); age, symptomatic, volume, multiple, edema
      were not. Male, recurrence, non-skull base, absence of calcification are
      independent risk factors for a high proliferative potential. These should be
      taken into consideration when managing meningiomas.

PMID- 16953449
TI  - Central neurocytoma: two case reports and review of the literature.
AB  - Central neurocytomas are low grade tumours usually located in the lateral
      ventricles next to Monro foramina. This paper reviews the literature on central
      neurocytomas observed in the last few years and discusses their clinical,
      histopathological, immunohistochemical and genetic characteristics. Important
      correlations between therapeutic strategies and biological findings as well as
      new genetic discoveries are also discussed. Two illustrative cases in which the
      authors report preliminary results about molecular analysis of some genetic
      markers are described.

PMID- 16953452
TI  - Experience with the transpalatal distractor in congenital deformities.
AB  - The transpalatal distractor is a bone-borne device that should eliminate negative
      orthodontic side-effects of tooth-borne devices. The literature contains reports
      of several possible complications of the transpalatal distractor. In this
      retrospective study its use was evaluated in ten patients with various congenital
      craniofacial anomalies, including clefts. During placement of the transpalatal
      distractor it was noted that in extremely narrow maxillae the palatal bone is
      very thin, which makes the initial placement difficult and therefore less primary
      stability can be obtained. There is often a thick palatal mucosa, which makes
      placement of the abutment plates difficult and leaves hardly any space for the
      module itself. Finally, in patients with mental retardation it is difficult to
      exchange modules and re-fix abutment plates. In our group of ten patients with
      congenital deformities a 60% complication rate was observed. The transpalatal
      distractor seems not to be the ideal device for use in widening the maxilla in
      cases with congenital deformities.

PMID- 16953451
TI  - Pathological laughter in trigeminal schwannoma: case report and review of the
      literature.
AB  - Pathological laughter is an uncommon manifestation of neurosurgical diseases.
      Very few cases of trigeminal schwannoma have been reported in the literature
      presenting with pathological laughter as a predominant symptom. We are reporting
      on a case of multi-compartmental trigeminal schwannoma presenting as pathological
      laughter and discuss a review of the literature. A 23-year-old lady presented
      with pathological laughter, along with symptoms pertaining to other cranial
      nerves and cerebellar dysfunction. Magnetic resonance imaging (MRI) of the brain
      was suggestive of a dumbbell-shaped mass in the middle and posterior cranial
      fossa on the left side, causing significant compression of the pons. She was
      investigated and operated for multi-compartmental trigeminal schwannoma.
      Following surgery, abnormal laughter disappeared immediately and no recurrence of
      symptoms was -present for a follow-up of 16 months. This case supports the role
      of the brainstem, especially the pons, in the control of laughter and, perhaps,
      of the medial temporal lobe too.

PMID- 16953453
TI  - [Overactive bladder syndrome. Are there indications for surgical therapy?].
AB  - Conservative therapeutic options are considered the gold standard in therapy of
      overactive bladder syndrome. However, surgery may be beneficial in selected
      cases. Neuromodulation is well established in clinical practice. If conservative
      or minimally invasive therapy fails, augmentation techniques or urinary diversion
      may be considered. This review presents the current knowledge about surgical
      treatment options for idiopathic overactive bladder.

PMID- 16953454
TI  - [Ancillary congress of AUA 2006. Annual meeting of the American Urological
      Association].

PMID- 16953455
TI  - Congenital intrathoracic kidney with right Bochdalek defect.
AB  - Intrathoracic kidney is a rare congenital anomaly. Since most reported cases are
      asymptomatic, it is extremely rare for this ectopia to be diagnosed in the
      neonatal period. We report a male infant with right intrathoracic kidney
      associated with Bochdalek defect. Chest X-ray demonstrated a right posterior
      mediastinal mass and intestinal gas in the right lung field. Contrast-enhanced CT
      and intravenous urography led to a diagnosis of intrathoracic kidney. Due to the
      presence of Bochdalek defect, the intrathoracic kidney was reduced into the
      abdominal cavity at the time of diaphragmatic repair. The intrathoracic kidney
      with attached adrenal gland was located at the level of the carina and was
      covered with protruded retroperitoneum. The kidney was thought to have been
      pushed this high by the small intestine and left lobe of the liver, which had
      also herniated through the defect. Postoperative hemodynamics and renal function
      were normal.

PMID- 16953456
TI  - Early bladder wall changes after creation of obstructive uropathy in the fetal
      lamb.
AB  - Vesico-amniotic shunting of obstructive uropathy in fetal lambs produced a thick
      walled, poorly compliant bladder. We report the early histological changes in the
      obstructed bladder wall. We created an obstructive uropathy in fetal lambs at 60
      days gestation by ligating the urethra and urachus. Vesicostomy or vesico
      amniotic shunt tube insertion and biopsy of the bladder wall were performed 21
      days later. The fetuses were delivered at term (145 days) and the kidneys and
      bladder sampled for histology. Colloidal iron (Col Fe), and alpha-smooth muscle
      actin (alpha-SMA) immunohistochemical stains were used for these samples.
      Seventeen fetuses were shunted with 15 biopsies taken at that time. Six (shunt
      failure or missed urachal ligation) were excluded. All biopsies taken at shunting
      had positive Col Fe and alpha-SMA. Term lambs had mild multicystic dysplastic
      kidney (MCDK) in five, severe MCDK in two, and hydronephrosis in four. All
      bladders had small volume and were severely fibrotic. Fetal shunt operations 3
      weeks after the creation of obstructive uropathy provided partial preservation of
      renal histology but did not preserve normal bladder histology. We suggest that
      the high hyaluronic acid synthesis activity or hyperplasia of the myofibroblasts
      in the dilated fetal bladder wall at the time of shunting results in irreversible
      damage to the developing bladder muscle and fibrosis.

PMID- 16953458
TI  - Distinguishing the noise and attractor strength of coordinated limb movements
      using recurrence analysis.
AB  - The variability of coupled rhythmic limb movements is assumed to be a consequence
      of the strength of a movement's attractor dynamic and a constant stochastic noise
      process that continuously perturbs the movement system away from this dynamic.
      Recently, it has been suggested that the nonlinear technique of recurrence
      analysis can be used to index the effects of noise and attractor strength on
      movement variability. To test this, three experiments were conducted in which the
      attractor strength of bimanual wrist-pendulum movements (using coordination mode,
      movement frequency and detuning), as well as the magnitude of stochastic
      perturbations affecting the variability of these movements (using a temporally
      fluctuating visual metronome) was manipulated. The results of these experiments
      demonstrate that recurrence analysis can index parametric changes in the
      attractor strength of coupled rhythmic limb movements and the magnitude of
      metronome induced stochastic perturbations independently. The results of
      Experiments 1 and 2 also support the claim that differences between the
      variability of inphase and antiphase coordination, and between slow and fast
      movement frequencies are due to differences in attractor strength. In contrast to
      the standard assumption that the noise that characterizes interlimb coordination
      remains constant for different magnitudes of detuning (Delta omega) the results
      of Experiment 3 suggest that the magnitude of noise increases with increases in
      |Delta omega|.

PMID- 16953457
TI  - Finasteride 1 mg has no inhibitory effect on omeprazole metabolism in extensive
      and poor metabolizers for CYP2C19 in Japanese.
AB  - OBJECTIVE: To examine the inhibitory effect of finasteride 1 mg on the metabolism
      of omeprazole in genetically determined extensive (EMs) and poor metabolizers
      (PMs) for CYP2C19 in young healthy Japanese male subjects. METHODS: Twenty-four
      volunteers participated in this study, among whom 12 were homozygous EMs and 12
      were PMs for CYP2C19. A single center, controlled, randomized, open, crossover
      study with a 5 day washout between the two study periods was performed. Each of
      the six EMs and PMs received a single oral 20 mg dose of omeprazole on day 1
      (treatment I). After a 5 day washout period, these subjects received 1 mg of
      finasteride once a day for three consecutive days, and a single oral 20 mg dose
      of omeprazole was co-administered on day 3 (treatment II). The 12 other EMs and
      PMs received treatments I and II in reverse. Plasma samples were collected for up
      to a 12 hours postdose of omeprazole, and the pharmacokinetic parameters of
      omeprazole were determined. RESULTS: The geometric mean ratio (GMR) for the
      AUC((0-12 hr)) of omeprazole when co-administered with finasteride/omeprazole
      alone is 1.13 (90%CI, 1.03, 1.25) and 0.96 (0.88, 1.05) in EMs and PMs,
      respectively. Finasteride did not significantly alter C(max), T(max) and t(1/2)
      in both genotypes. CONCLUSION: Finasteride 1 mg, widely used for the treatment of
      androgenetic alopecia in men, did not meaningfully increase omeprazole exposure
      (20 mg) in both EMs and PMs for CYP2C19. These results indicate that finasteride
      does not meaningfully inhibit CYP2C19 activity in vivo at the dose of 1 mg.

PMID- 16953459
TI  - Morphological pattern and frequency of intracranial tumors in children.
AB  - BACKGROUND: Brain tumors are the second most common neoplasm in children. Pattern
      of primary brain tumors in children has not been reported in Iran. Brain tumors
      have been the subject of controversy both with respect to pattern of occurrence
      and to potential causes. OBJECTIVE: To determine the age, sex, location, and
      histologic diagnosis of intracranial tumors in children less than 15 years of
      age. MATERIALS AND METHODS: A retrospective study of 619 children who were
      admitted to the neurosurgical center between 1978 and 2003 was performed. Charts
      were reviewed to extract information about demographics, location, and
      histopathological diagnosis of tumors. All patients entered into this study had
      pathologically proven brain tumor. The frequency distribution of brain tumors by
      age and sex, location, and histopathology was calculated. RESULTS: The male
      female ratio, 58.1 to 41.9%, vary significantly (p<0.05). The mean age of the
      patients at time of diagnosis was 8.8 years (SD=3.9). Fifty-one percent of brain
      tumors were located in supratentorial, and 49.0% in the infratentorial region. In
      supratentorial region, 57.0% of the tumors were in the hemispheric. In
      infratentorial region, 68% of the tumors were in the midline. The mixed five most
      common histological diagnoses in patients were astrocytoma (40.4%), followed by
      medulloblastoma (18.4%), ependymoma (10.5%), craniopharyngioma (8.8%), and
      meningioma (4.2%). Most of the brain tumor types (85%) occurred in children
      between 5 to 15 years of age. Astrocytoma occurred mostly in children aged 5-15
      years (87%). CONCLUSION: Males were affected more than females. A significant
      male predominance was observed in craniopharyngioma and medulloblastoma.
      Astrocytoma was the first most common brain tumor in all age groups. Certain
      tumor types show a predilection for the certain period of life.

PMID- 16953460
TI  - Tissue microarrays as a platform for proteomic investigation.
AB  - Tissue microarrays have become an essential tool in translational pathology. They
      are used to confirm results from other experimental platforms, such as expression
      microarrays, as well as a primary tool to explore the expression profile of
      proteins by immunohistochemical analysis. Tissue microarrays are routinely used
      molecular epidemiology, drug development and determining the diagnostic,
      prognostic and predictive value of new biomarkers. By applying traditional
      protein based assays, as well as novel assays to the platform, tissue microarrays
      have gained a new utility as a proteomic tool for both basic science as well as
      clinical investigation. This article will explore the new approaches that are
      being applied to tissue microarrays to, characterize the human proteome, and new
      technologies that allow tissue microarrays to function as a protein array.

PMID- 16953462
TI  - What do we know about cognitive and motivational effects of small group tutorials
      in problem-based learning?
AB  - Students collaborating in small groups is a characteristic of problem-based
      learning (PBL) that is receiving increased consideration in the literature. In
      this paper findings from studies in this area are synthesized and discussed. A
      distinction is made between studies focusing on cognitive effects of group
      learning and studies focusing on motivational effects of group learning. Studies
      concentrating on the cognitive effects of small-group PBL seem to demonstrate
      that activation of prior knowledge, recall of information, causal reasoning or
      theory building, cognitive conflicts leading to conceptual change and
      collaborative learning construction take place in the tutorial group. Studies
      focusing on the motivational effects of PBL demonstrate that group discussion
      positively influences students' intrinsic interest in the subject matter under
      discussion. The studies also demonstrate that a haphazard discussion in the
      tutorial group or a discussion that just scratches the surface, probably caused
      by students being less motivated, inhibits student learning. Several studies are
      reported providing suggestions on how to optimize group work in PBL. Although the
      studies demonstrate that group learning in PBL may have positive effects, much
      more research is needed to obtain more evidence and deeper insight in the
      cognitive and emotional effects of small group learning in PBL.

PMID- 16953463
TI  - The influence of catecholamines on pseudocholinesterase enzymatic activity.
      Results of a laboratory investigation.
AB  - OBJECTIVE: Acceleratory and inhibitory receptors have been described on the
      pseudocholinesterase (PCHE) molecule. An increased PCHE activity has been
      reported in patients with chronic pain and anxiety, conditions known to be
      correlated with increased plasma catecholamine levels. Aim of this laboratory
      investigation was to determine whether catecholamines have an effect on PCHE
      activity, as this knowledge could help to define the role of PCHE in the
      assessment of stress. METHODS: After Ethics committee approval and written
      informed consent, 3 ml of blood was collected from five healthy volunteers.
      Fourteen samples of 50 mul each were prepared from each of the volunteer's
      plasma. Epinephrine (25, 50, 100, 200, 400 and 1000 pg) and norepinephrine (50,
      100, 200, 400, 800 and 2000 pg) were added to samples of each subject. Sodium
      chloride solution was added to control samples. PCHE activity was photometrically
      assessed. RESULTS: PCHE activity was significantly higher after the addition of
      epinephrine (median 8304 versus 7386 U/l). This effect was not dose-dependent.
      PCHE activity did not change after addition of norepinephine. CONCLUSIONS: This
      mechanism might explain previous findings that showed higher levels of PCHE
      activity in the presence of chronic pain and anxiety. In the absence of a dose
      response curve in the concentration range studied, PCHE activity does not appear
      to be suitable for the assessment of levels of stress.

PMID- 16953464
TI  - Endometrial thickness and volume by three-dimensional ultrasound one week after
      embryo transfer to detect pregnancy.
AB  - PURPOSE: Determine if the evaluation of endometrium one week after embryo
      transfer can predict pregnancy. METHODS: Endometrial volume and thickness were
      evaluated by three-dimensional ultrasound in 40 patients one week after embryo
      transfer. These results were compared to serum pregnancy test performed one week
      later. RESULTS: Twenty two patients have achieved pregnancy. A significant
      difference was found for endometrial volume: 6.49+/-1.97 mL vs. 3.40+/-1.11 mL
      (pregnant vs. not pregnant); and thickness: 11.15+/-2.75 mm vs. 9.77+/-1.85 mm.
      The ROC curve was used to detect the best cutoff values: endometrial volume of
      3.48 mL (sensitivity-100%, specificity-68.2%) and endometrial thickness of 10.3
      mm (sensitivity-72.2%, specificity-77.3%). The area under curve was significant
      higher for endometrial volume (0.909 vs. 0.745, P=0.027). No pregnancy was
      achieved in women who had an endometrial volume <3.8 mL (15 patients) or
      thickness < 7.9 mm (3 patients). CONCLUSIONS: The endometrial volume and
      thickness were significant higher in pregnant women and this difference was more
      prominent for endometrial volume.

PMID- 16953466
TI  - Antihyperuricemic lignans from the leaves of Phyllanthus niruri.
AB  - The methanol extract from the leaves of Phyllanthus niruri L. showed oral
      antihyperuricemic activity in potassium oxonate- and uric acid-induced
      hyperuricemic rats. Fractionation of the extract by resin chromatography led to
      the isolation of a less polar fraction which exhibited the highest reduction of
      plasma uric acid. Further antihyperuricemic-guided purification of the fraction
      afforded three lignans, phyllanthin (1), hypophyllanthin (2) and phyltetralin
      (3), of which 1 significantly reversed the plasma uric acid level of
      hyperuricemic animals to its normal level in a dose-dependent manner, comparable
      to that of allopurinol, benzbromarone and probenecid which are used clinically
      for the treatment of hyperuricemia and gout. Thus, the lignans of P. niruri are
      potential antihyperuricemic agents worthy of further investigation.

PMID- 16953467
TI  - [Imaging features of diffuse pulmonary hemorrhage].

PMID- 16953477
TI  - [Fetal resonance imaging].

PMID- 16953478
TI  - [Characteristics and applications of a flat panel computer tomography system].
AB  - PURPOSE: To assess a new flat panel volume computed tomography (FP-VCT) with very
      high isotropic spatial resolution as well as high Z-axis coverage. MATERIALS AND
      METHODS: The prototype of an FP-VCT scanner with a detector cell size of 0.2 mm
      was used for numerous phantom studies, specimen examinations, and animal research
      projects. RESULTS: The high spatial resolution of the new system can be used to
      accurately determine solid tumor volume, thus allowing for earlier assessment of
      the therapeutic response. In animal experimentation, whole-body perfusion mapping
      of mice is feasible. The high spatial resolution also improves the classification
      of coronary artery atherosclerotic plaques in the isolated post mortem human
      heart. With the depiction of intramyocardial segments of the coronary arteries,
      investigations of myocardial collateral circulation are feasible. In skeletal
      applications, an accurate analysis of the smallest bony structures, e. g.,
      petrous bone and dental preparations, can be successfully performed, as well as
      investigations of repetitive studies of fracture healing and the treatment of
      osteoporosis. CONCLUSION: The introduction of FP-VCT opens up new applications
      for CT, including the field of molecular imaging, which are highly attractive for
      future clinical applications. Present limitations include limited temporal
      resolution and necessitate further improvement of the system.

PMID- 16953479
TI  - [CT-based software-supported prediction of the postoperative lung function after
      partial resection of the lung].
AB  - PURPOSE: The predicted postoperative forced exspiratory volume in one second (FEV
      (1)) is an important functional factor for predicting the operability of patients
      with bronchial carcinoma. A software tool that uses a preoperative chest MSCT and
      pulmonary function test (PFT) for largely automated prediction of the FEV (1) was
      evaluated. MATERIALS AND METHODS: Fifteen patients with surgically treated lung
      cancer were examined with a preoperative chest MSCT (1.25 mm slice thickness, 0.8
      mm reconstruction increment) and PFT before and after surgery. CT scans were
      analyzed by the prototype software MeVisPulmo (MeVis gGmbH, Bremen) that
      predicted the postoperative FEV (1) as a percentage of the preoperative values
      measured by PFT. The automated segmentation and volumetry of lung lobes were
      performed either without or with minimal user interaction. Patients underwent
      lobectomy in twelve cases (6 upper lobes, 1 middle lobe, 5 lower lobes) and
      pneumectomy in three cases. The predicted FEV (1) values were compared to the
      observed postoperative values as a standard of reference. The additional
      functional parameters "total lung capacity" (TLC) and "forced vital capacity"
      (FVC) were compared to the FEV (1) results. RESULTS: Automated calculation of
      predicted postoperative lung function was successful in all cases. Due to an
      implausible PFT, two of the 15 patients were excluded from the collective. A mean
      postoperative FEV (1) value of 75 % (SD +/- 12 %) of the preoperative FEV (1) was
      calculated and 74 % (SD +/- 12 %) was actually measured. The deviations of the
      predicted value from the measured postoperative FEV (1) ranged between - 289 ml (
      12 % of the measured postoperative FEV (1)) and + 294 ml (+ 15 % of the
      postoperative FEV (1)). The mean deviation (absolute value) was 137 +/- 77 ml/s.
      This corresponds to 7 +/- 3 % of the measured postoperative FEV (1). Bland-Altman
      Statistics showed the 95 % "limits of agreement" for the predicted FEV (1) values
      to be between - 341 ml and + 301 ml, corresponding to - 17.5 % and + 15.8 of the
      measured postoperative FEV (1) value. Analysis of the TLC and FVC yielded similar
      results. CONCLUSION: In the present pilot study the software-assisted prediction
      of the postoperative FEV (1) using a preoperative MSCT and pulmonary function
      test corresponded satisfactorily with the observed postoperative values. The
      introduced approach may make it possible to obtain additional information for the
      prediction of functional operability prior to performing lung cancer surgery.

PMID- 16953480
TI  - [Radiation exposure with 3D rotational angiography of the skull].
AB  - PURPOSE: Determination and comparison of radiation exposure for examinations of
      the skull with unsubtracted 3D Rotational Angiography (3D RA) and 2D Digital
      Subtraction Angiography (2D DSA). MATERIALS AND METHODS: Measurements were
      carried out with a skull of an Alderson phantom for 3D RA and for 2D DSA in p. a.
      and lateral projections using an Innova 4100 angiography system with a digital
      flat panel detector from GE Healthcare. 45 thermoluminescent dosimeters TLD 100H
      from Harshaw were placed inside the phantom to measure organ doses. In addition
      the dose area product was recorded and the effective dose was calculated using
      the Monte Carlo program PCXMC. RESULTS: For a biplanar DSA run (lateral and p. a.
      projection), the organ doses were 4 to 5 times higher and the effective dose was
      4 times higher than for a 3D RA even though the number of images for the two DSA
      runs was only half of that for 3D RA. CONCLUSION: The radiation exposure for
      unsubtracted 3D RA using a flat panel detector is significantly lower than for
      biplanar DSA. Using 3D RA in place of 2D DSA can reduce the radiation exposure of
      patients in neuroradiology procedures.

PMID- 16953481
TI  - [Functional imaging of submandibular glands: diffusion-weighted echo-planar MRI
      before and after stimulation].
AB  - PURPOSE: To investigate the feasibility of diffusion-weighted (DWI) echo-planar
      imaging (EPI) to depict the submandibular glands and to measure different
      functional conditions. MATERIALS AND METHODS: Twenty-seven healthy volunteers
      were examined. Diffusion weighted sequence was performed prior to stimulation.
      Exactly 30 seconds after a commercially available lemon juice was given orally,
      the diffusion weighted sequence was repeated. All examinations were performed by
      using a 1.5-T superconducting system with a 30 mT/m maximum gradient capability
      and maximum slew rate of 125 mT/m/sec (Magnetom Symphony, Siemens, Erlangen,
      Germany). The lower part of the circularly polarized (CP) head coil and a
      standard two-element CP neck array coil were used. The flexibility of the neck
      array coil allowed positioning the N1 element (upper part of the coil) right next
      to the submandibular gland. The axial diffusion-weighted EPI (echo planar
      imaging) sequence was performed using a matrix of 119 x 128, a field of view of
      250 x 250 mm (pixel size 2.1 x 1.95 mm), a section thickness of 5 mm with an
      interslice gap of 1 mm. The b factors used were 0 sec/mm(2), 500 sec/ mm(2) and
      1000 sec/mm(2). Apparent diffusion coefficiant (ADC) maps were digitally
      transferred to MRIcro (Chris Rorden, Universitiy of Nottingham, Great Britain).
      After detecting the submandibular glands a region of interest (ROI) was placed
      manually exactly within the boarder of both submandibular glands, excluding the
      external carotid artery on ADC maps. These procedures were performed on all ADC
      slices the submandibular glands could be differentiated in before and after oral
      stimulation. For statistical comparison of results, a student's t-test was
      performed with an overall two-tailed significance level of p = 0.05. RESULTS: The
      visualization of the submandibular glands using the diffusion-weighted EPI
      sequence was possible in all of the 27 volunteers. Prior to oral stimulation an
      ADC of 1.31 x 10(-3) mm(2)/sec (95 % CI, 1.39 x 10(-3) mm(2)/sec, 1.44 x 10(-3)
      mm(2)/sec) was calculated which increased to 1.41 x 10(-3) mm(2)/sec (95 % KI,
      1.39 x 10(- 3) mm(2)/sec, 1.44 x 10(-3) mm(2)/sec) 30 seconds after stimulation.
      This increase proved to be significant (p < 0.001). CONCLUSION: Diffusion
      weighted echo-planar MR imaging allows non-invasive quantification of functional
      changes in the submandibular gland.

PMID- 16953482
TI  - [Mammographic and ultrasonographic features of metastases of malignant melanoma
      of the breast].

PMID- 16953486
TI  - The relation of psychopathy to concurrent aggression and antisocial behavior in
      high-risk adolescent girls and boys.
AB  - The present study examined the concurrent relationship between psychopathy
      characteristics as measured by the PCL:YV and aggressive and antisocial behavior
      in a sample of 142 high-risk adolescent girls and boys. The unique relationship
      between each of three PCL:YV factors (Arrogant and Deceitful Interpersonal Style,
      Deficient Affective Experience, and Impulsive and Irresponsible Behavioral Style)
      and outcomes was evaluated to determine which aspects of psychopathy are most
      crucially linked to aggressive and antisocial behavior in adolescents. Dependent
      measures were expanded to include both relational and physical forms of
      aggression to better capture meaningful outcomes for girls and boys. Regression
      analyses showed that the relationships between psychopathic features and outcomes
      were equivalent for boys and girls, and that deficits in affect were most
      consistently associated with aggression. These findings are concordant with the
      well established finding in developmental research showing that deficits in
      empathy and affect regulation are associated with aggression.

PMID- 16953487
TI  - Ultrasonographically guided surgical approach to liver tumours involving the
      hepatic veins close to the caval confluence.
AB  - BACKGROUND: Intraoperative ultrasonography (IOUS) may allow a more conservative
      procedure in patients with liver tumours involving a hepatic vein at the caval
      confluence. The aim of this study was to determine whether IOUS and colour
      Doppler IOUS might reduce the rate of major hepatectomy and vascular
      reconstruction in patients with such tumours. METHODS: Of 133 consecutive
      patients with a liver tumour who underwent hepatectomy, 22 had involvement of a
      hepatic vein at the caval confluence. The surgical strategy employed was
      determined by IOUS findings of the relationship between the tumour and hepatic
      vein, the presence of accessory veins, and portal flow as measured by colour
      Doppler IOUS following clamping of the hepatic vein to be resected. Mortality,
      morbidity, major resection, hepatic vein reconstruction and local recurrence
      rates were evaluated. RESULTS: There were no hospital deaths and only one patient
      suffered major morbidity. Although hepatic vein resection was performed in 15
      patients, only two underwent major hepatectomy and none had vascular
      reconstruction. No patients had tumour recurrence at a mean follow-up of 23
      months. CONCLUSION: IOUS allowed sparing of the liver parenchyma without tumour
      recurrence in most patients with a tumour involving a hepatic vein at the caval
      confluence, avoiding more extensive hepatectomy or vascular reconstruction.

PMID- 16953488
TI  - Diverting multi-problem youth from juvenile justice: investigating the importance
      of community influence on placement and recidivism.
AB  - In the U.S., diversion has increasingly become one of the most utilized
      alternatives to detention of delinquent youth. Programs providing diversion can
      vary greatly. Variations in program design make it difficult to evaluate the
      effectiveness of program outcomes. Utilizing hierarchical linear modeling, this
      study examines variations in outcome for ten program sites of the New York State
      MH/JJ Diversion Project. Program and youth predictors were evaluated on two
      outcomes: out-of- community placement and recidivism. At the individual level,
      significant mental health and substance abuse problems, age, prior placements,
      and use of wraparound funds were predictive of youth placements, while
      significant substance abuse problems were predictive of recidivism. Program
      variations were found to have a significant impact on youth outcomes.
      Specifically, sites providing direct (or "in house") care had significantly
      reduced rates of placement. Study results and implications for future research
      are discussed.

PMID- 16953489
TI  - Velvetbean (Mucuna pruriens) extracts: impact on Meloidogyne incognita survival
      and on Lycopersicon esculentum and Lactuca sativa germination and growth.
AB  - Velvetbean (Mucuna spp.) is a summer annual that has been used as a cover crop to
      reduce erosion, fix nitrogen and suppress weeds and plant-parasitic nematodes.
      Crude aqueous extracts (1:15 dry weight plant/volume water) were made from
      velvetbean plant parts, and various concentrations of the extracts were evaluated
      in vitro for toxicities to different stages of Meloidogyne incognita (Kofoid and
      White) Chitwood and for suppression of hypocotyl and root growth and inhibition
      of germination of tomato (Lycopersicon esculentum L.) and lettuce (Lactuca sativa
      L.). Germination was only affected by the full-strength extract from leaf blades.
      Lettuce root growth was the most sensitive indicator of allelopathic activity of
      the plant part extracts. Lettuce and tomato root growth was more sensitive to the
      extract from main roots than to extracts of other plant parts, with lethal
      concentration (LC50) values of 1.2 and 1.1% respectively. Meloidogyne incognita
      egg hatch was less sensitive to extracts from velvetbean than the juvenile (J2)
      stage. There was no difference among LC50 values of the extracts from different
      plant parts against the egg stage. Based on LC50 values, the extract from fine
      roots was the least toxic to J2 (LC50 39.9%), and the extract from vines the most
      toxic (LC50 7.8%). The effects of the extracts were nematicidal because LC50
      values did not change when the extracts were removed and replaced with water.

PMID- 16953490
TI  - Impact of spray application methodology on the development of resistance to
      cypermethrin and spinosad by fall armyworm Spodoptera frugiperda (JE Smith).
AB  - The development of resistance to an insecticide under various types of
      application method has yet to be reported in the literature. Five fall armyworm
      Spodoptera armigera (JE Smith) colonies were reared in a chamber for ten
      generations before starting topical application bioassays. From each colony, 200
      500 third-fourth-instar larvae were fed for 72 h on corn plants sprayed with
      cypermethrin or spinosad at minimum application rate (20 g ha(-1)) using a small
      droplet size nozzle XR8001VS (volume median diameter D(v0.5) = 163 microm) or a
      large droplet size nozzle XR8008VS (D(v0.5) = 519 microm). Surviving larvae were
      transferred to untreated corn leaves to complete their life cycle. Next
      generation third-instar larvae of each colony were topically dosed with technical
      cypermethrin or spinosad at 1 microL per larva, and mortality was recorded 24 h
      post-treatment. The results indicated that cypermethrin demonstrated an
      insecticidal activity greater than that of spinosad, and the cypermethrin
      regression lines moved to the right faster than those for spinosad, indicating an
      increased tolerance of cypermethrin. Generally, larvae from all generations (F1
      F7) under the XR8008VS treatments were less susceptible to cypermethrin and
      developed resistance faster and to higher levels than larvae from the XR8001VS
      treatments. The confidence limits (95%) of LD(50) for all spinosad treatments
      indicated that there was no significant difference from the LD(50) value of the
      susceptible reference strain. The results are a first indication that application
      technology/insecticide reaction may affect the rapidity of resistance development
      in certain pest/plant scenarios, but field studies are needed to confirm this
      conclusion.

PMID- 16953491
TI  - Insecticide resistance in vector mosquitoes in China.
AB  - Because of their special behaviour, physiology and close relationship with
      humans, mosquitoes act as one of the most important vectors of human diseases,
      such as filariasis, Japanese encephalitis, dengue and malaria. The major vector
      mosquitoes are members of the Culex, Aedes and Anopheles genera. Insecticides
      play important roles in agricultural production and public health, especially in
      a country with a huge human population, like China. Large quantities of four
      classes of insecticides, organochlorines, organophosphates, carbamates and
      pyrethroids, are applied annually to fields or indoors in China, directly or
      indirectly bringing heavy selection pressure on vector populations. The seven
      major species of vector mosquito in China are the Culex pipiens L. complex, C.
      tritaeniorhynchus Giles, Anopheles sinensis Wied., A. minimus Theobald, A.
      anthropophagus Xu & Feng, Aedes albopictus (Skuse) and Ae. aegypti L., and all
      have evolved resistance to all the above types of insecticide except the
      carbamates. The degree of resistance varies among mosquito species, insecticide
      classes and regions. This review summarizes the resistance status of these
      important vector mosquitoes, according to data reported since the 1990s, in order
      to improve resistance management and epidemic disease control, and to communicate
      this information from China to the wider community.

PMID- 16953492
TI  - Synthesis of analogues of anthraquinones linked to tuftsin or retro-tuftsin
      residues as potential topoisomerase inhibitors.
AB  - A novel group of [(4-, 5- or 8)-hydroxy-9,10-anthraquinone-1-yl]-(tuftsin or
      retro-tuftsin) acids and methyl esters has been synthesized as potential
      anticancer compounds. The corresponding protected tuftsin or retro-tuftsin
      derivatives were also synthesized. We hope that combining compounds of different
      mechanisms of action will improve their clinical properties, and that our new
      analogues will be much more effective against multidrug-resistant tumour cell
      lines.

PMID- 16953493
TI  - Differential aphicidal effects of chitinase inhibitors on the polyphagous
      homopteran Myzus persicae (Sulzer).
AB  - Four chitinase inhibitors, cyclo-(Proline-Tyrosine), cyclo-(Histidine-Proline),
      allosamidin and psammaplin A, were selected for in vitro feeding experiments with
      the peach-potato aphid, Myzus persicae (Sulzer), under controlled photoperiod and
      temperature conditions. Artificial diets were used to provide chitinase
      inhibitors at 10, 50 and 100 microg mL(-1) to M. persicae. Except for cyclo
      (Proline-Tyrosine), which did not modify aphid demographic parameters, chitinase
      inhibitors induced differential aphicidal effects on M. persicae. At all doses,
      cyclo-(Histidine-Proline) induced significant effects affecting daily fecundity,
      intrinsic rate of natural increase (r(m)) and doubling time of population. When
      compared with the control diet, allosamidin decreased nymph survival and daily
      fecundity, increasing the doubling time of population from 1 to 1.5 days.
      Psammaplin A was the most toxic inhibitor when delivered via artificial diet, as
      it induced the death of all aphids reared at 50 and 100 microg mL(-1). The
      results demonstrate the potential use of chitinase inhibitors as aphid management
      tools.

PMID- 16953494
TI  - Activities of mixtures of soil-applied herbicides with different molecular
      targets.
AB  - The joint action of soil-applied herbicide mixtures with similar or different
      modes of action has been assessed by using the additive dose model (ADM). The
      herbicides chlorsulfuron, metsulfuron-methyl, pendimethalin and pretilachlor,
      applied either singly or in binary mixtures, were used on rice (Oryza sativa L.).
      The growth (shoot) response curves were described by a logistic dose-response
      model. The ED50 values and their corresponding standard errors obtained from the
      response curves were used to test statistically if the shape of the isoboles
      differed from the reference model (ADM). Results showed that mixtures of
      herbicides with similar molecular targets, i.e. chlorsulfuron and metsulfuron
      (acetolactate synthase (ALS) inhibitors), and with different molecular targets,
      i.e. pendimethalin (microtubule assembly inhibitor) and pretilachlor (very long
      chain fatty acids (VLCFAs) inhibitor), followed the ADM. Mixing herbicides with
      different molecular targets gave different results depending on whether
      pretilachlor or pendimethalin was involved. In general, mixtures of pretilachlor
      and sulfonylureas showed synergistic interactions, whereas mixtures of
      pendimethalin and sulfonylureas exhibited either antagonistic or additive
      activities. Hence, there is a large potential for both increasing the specificity
      of herbicides by using mixtures and lowering the total dose for weed control,
      while at the same time delaying the development of herbicide resistance by using
      mixtures with different molecular targets.

PMID- 16953495
TI  - Solid-phase synthesis of C-terminally modified peptides.
AB  - In this paper, a straightforward and generic protocol is presented to label the C
      terminus of a peptide with any desired moiety that is functionalized with a
      primary amine. Amine-functional molecules included are polymers (useful for
      hybrid polymers), long alkyl chains (used in peptide amphiphiles and
      stabilization of peptides), propargyl amine and azido propyl-amine (desirable for
      'click' chemistry), dansyl amine (fluorescent labeling of peptides) and crown
      ethers (peptide switches/hybrids). In the first part of the procedure, the
      primary amine is attached to an aldehyde-functional resin via reductive
      amination. To the secondary amine that is produced, an amino acid sequence is
      coupled via a standard solid-phase peptide synthesis protocol. Since one
      procedure can be applied for any given amine-functional moiety, a robust method
      for C-terminal peptide labeling is obtained.

PMID- 16953496
TI  - Bioactivity of extracts and isolated compounds from Vitex polygama (Verbenaceae)
      and Siphoneugena densiflora (Myrtaceae) against Spodoptera frugiperda
      (Lepidoptera: Noctuidae).
AB  - The effects of crude extracts, fractions and isolated compounds from Vitex
      polygama Cham. and Siphoneugena densiflora Berg were evaluated on the development
      of Spodoptera frugiperda JE Smith, a destructive insect pest of corn and several
      other crops. The extracts and fractions were incorporated into an artificial diet
      at 1 mg g(-1) and offered to the insect during its larval stage. Length and
      viability of larval and pupal stages as well as pupal weight were assessed.
      Isolated compounds were tested through superficial contamination of the diet at
      0.1 mg g(-1). Weight and viability of ten-day-old larvae were determined.
      Methanolic and hydroalcoholic S. densiflora extracts caused 100% larval
      mortality, while leaf and fruit hydroalcoholic extracts from V. polygama were the
      most active. Among the isolated compounds, flavonoids presented the best
      insecticidal results, and tannins the best larval growth inhibition.

PMID- 16953497
TI  - Real-time quantitative PCR assays for quantification of L1781 ACCase inhibitor
      resistance allele in leaf and seed pools of Lolium populations.
AB  - The I1781L amino acid substitution in the target ACCase enzyme causes broad
      resistance to ACCase inhibitor herbicides in several monocotyledenous weeds of
      agronomic importance. This mutation results from a substitution of an adenine (A)
      residue by either a thymine (T) or cytosine (C) at position 5341 in Alopecurus
      myosuroides Huds and at an equivalent position in Lolium species, Avena fatua L.
      and Setaria viridis (L.) Beauv. Two different procedures, the PCR-based allele
      specific assay (ASA) and the derived cleaved amplified polymorphic sequence
      (dCAPS) method, have previously been described for detecting this mutation. These
      methods are, however, only amenable to low sample throughput and are used in the
      analysis of single plants. Here, an alternative high-throughput ARMS/Scorpion
      real-time quantitative PCR (Q-PCR) method for measuring levels of the I1781L
      mutation in pools of leaf and seed samples of Lolium populations is presented.
      The limit of detection for C and T mutant alleles in a background of wild-type A
      is 0.02 and 0.0003% respectively. In this study, DNA from batches of 24 leaf
      segments measuring 0.5 cm from different plants or 1000 seeds could be
      conveniently extracted and accurately analysed. As part of assay validation, the
      comparative analysis of five geographically distinct Lolium populations with
      dCAPS and Q-PCR procedures demonstrated the accuracy of the latter method, and
      the three possible II1781, IL1781 and LL1781 ACCase genotypes being distributed
      as predicted by the Hardy-Weinberg principle. Given the dominance of the L1781
      over the I1781 allele at recommended field rates for most ACCase inhibitors, the
      frequency of herbicide survivors in the field owing only to the presence of the
      I1781L mutation is thus predicted to be 2pq + q(2), where p and q are the
      frequencies of the I1781 and L1781 alleles as determined by Q-PCR. The Q-PCR
      assay established allows detection of very low levels of the L1781 ACCase
      mutation before resistance would normally be discernible in the field. Therefore,
      it offers the opportunity to tackle resistance at its very onset, potentially
      avoiding implementation of complicated and often costly weed management
      practices.

PMID- 16953498
TI  - A new fluorescent probe for zinc(II): an 8-hydroxy-5-N,N
      dimethylaminosulfonylquinoline-pendant 1,4,7,10-tetraazacyclododecane.
AB  - A new fluorescent probe for Zn2+, namely, 8-hydroxy-5-N,N
      dimethylaminosulfonylquinolin-2-ylmethyl-pendant cyclen (L8), was designed and
      synthesized (cyclen=1,4,7,10-tetraazacyclododecane). By potentiometric pH, 1H
      NMR, and UV spectroscopic titrations, the deprotonation constants pKa1-pKa6 of
      L(8)4 HCl were determined to be <2, <2, <2 (for amino groups of the cyclen and
      quinoline moieties), 7.19+/-0.05 (for 8-OH of the quinoline moiety), 10.10+/
      0.05, and 11.49+/-0.05, respectively, at 25 degrees C with I=0.1 (NaNO3). The
      results of 1H NMR, potentiometric pH, and UV titrations, as well as single
      crystal X-ray diffraction analysis, showed that L8 and Zn2+ form a 1:1 complex
      [Zn(H-1L8)], in which the 8-OH group of the quinoline ring of L8 is deprotonated
      and coordinates to Zn2+, in aqueous solution at neutral pH. On addition of one
      equivalent of Zn2+ and Cd2+, the fluorescence emission of L8 (5 microM) at 512 nm
      in aqueous solution at pH 7.4 [10 mM HEPES with I=0.1 (NaNO3)] and 25 degrees C
      increased by factors of 17 and 43, respectively. We found that the cyclen moiety
      has the unique property of quenching the fluorescence emission of the quinolinol
      moiety when not complexed with metal cations, but enhancing emission when
      complexed with Zn2+ or Cd2+. In addition, the Zn2+-L8 complex [Zn(H-1L8)] is much
      more thermodynamically and kinetically stable (Kd{Zn(H
      1L8)}=[Zn2+]free[L8]free/[Zn(H-1L8)]=8 fM at pH 7.4) than the Zn2+ complexes of
      our previous Zn2+ fluorophores ([Zn(H-1L2)] and [Zn(L3)]). Furthermore, formation
      of [Zn(H-1L8)] is much faster than those of [Zn(H-1L2)] and [Zn(L3)]. The
      staining of early-stage apoptotic cells with L8 is also described.

PMID- 16953499
TI  - New insights into the classic chiral Grignard reagent (1R,2S,5R)-menthylmagnesium
      chloride.

PMID- 16953500
TI  - Organocatalytic enantioselective nucleophilic vinylic substitution.

PMID- 16953501
TI  - One-step synthesis of benzotetra- and benzopentacyclic compounds through
      intramolecular [2+3] photocycloaddition of alkenes to naphthalene.

PMID- 16953502
TI  - Template-free, low-temperature synthesis of crystalline barium titanate
      nanoparticles under bio-inspired conditions.

PMID- 16953503
TI  - Coupling-isomerization synthesis of chalcones.
AB  - The Sonogashira coupling of electron-deficient (hetero)aryl halides 1 and
      (hetero)aryl or alkenyl 1-propargyl alcohols 2 does not terminate at the stage of
      the expected internal propargyl alcohols, but rather gives rise to the formation
      of alpha,beta-unsaturated ketones 3 with a variety of acceptor substituents. This
      new domino reaction, a coupling-isomerization reaction (CIR), can be rationalized
      as a sequence of rapid Pd/Cu-catalyzed alkynylation followed by a slow amine-base
      catalyzed propargyl alcohol-enone isomerization. Performing the CIR in deuterated
      protic solvents or with a selectively deuterated propargyl alcohol revealed that
      the base-catalyzed isomerization step proceeds through a formal 1,3-H shift with
      minimal H/D exchange with the surrounding solvent. Additionally, 19F NMR kinetic
      measurements on the isomerization step with the fluorinated propargyl alcohol 4 r
      support the mechanistic rationale.

PMID- 16953504
TI  - Interaction of zinc oxide clusters with molecules related to the sulfur
      vulcanization of polyolefins ("rubber").
AB  - The vulcanization of rubber by sulfur is a large-scale industrial process that is
      only poorly understood, especially the role of zinc oxide, which is added as an
      activator. We used the highly symmetrical cluster Zn(4)O(4) (T(d)) as a model
      species to study the thermodynamics of the initial interaction of various
      vulcanization-related molecules with ZnO by DFT methods, mostly at the B3LYP/6
      31+G* level. The interaction energy of Lewis bases with Zn(4)O(4) increases in
      the following order: CO<S(6)<C(2)H(4)<C(3)H(6)<Me(2)S(2)<1,4
      C(5)H(8)<MeSH<Me(2)O<Me(2)S<Me(3)N<<CH(3)COO(-). The corresponding binding
      energies range from -57 to -262 kJ mol(-1). However, Bronsted acids react with
      the Zn(4)O(4) cluster with proton transfer from the ligand molecule to one of the
      oxygen atoms of Zn(4)O(4), and these reactions are all strongly exothermic
      [binding energies [kJ mol(-1)] in parentheses: H(2)O (-183), MeOH (-171), H(2)S (
      245), MeSH (-230), C(3)H(6) (-121), and CH(3)COOH (-255)]. The important
      vulcanization accelerator mercaptobenzothiazole (C(7)H(5)NS(2), MBT) containing
      several donor sites reacts with the Zn(4)O(4) cluster with proton transfer from
      the NH group to one of the oxygen atoms of ZnO, and in addition the exocyclic
      thiono sulfur atom and the nitrogen atom coordinate to one and the same zinc
      atom, resulting in a binding energy of -247 kJ mol(-1). A second isomer of
      [(MBT)Zn(4)O(4)] with a strong O--HN hydrogen bond rather than a Zn--N bond is
      only slightly less stable (binding energy -243 kJ mol(-1)). The NH form of free
      MBT is 36 kJ mol(-1) more stable than the tautomeric SH form, while the
      sulfurized MBT derivative benzothiazolyl hydrodisulfide C(7)H(5)NS(3) (BtSSH) is
      most stable with the connectivity >CSSH.

PMID- 16953505
TI  - Total solid-phase synthesis of the azathiocoraline class of symmetric bicyclic
      peptides.
AB  - Thiocoraline is a potent antitumor agent isolated from the marine organism
      Micromonospora sp. This symmetric bicyclic depsipeptide binds the minor groove of
      DNA. Here we report two solid-phase strategies for the syntheses of
      azathiocoraline and its analogues. The thioester linkage was replaced by an amide
      bond to improve the compound's pharmacokinetic properties. The first strategy is
      based on a convergent (4+4) approach, whilst the second is a stepwise synthesis,
      cyclizations in both approaches occurring on the solid support. These two
      strategies were designed to overcome problems caused by the presence of
      consecutive noncommercial N-methyl amino acids, to avoid epimerization during
      cyclization and/or fragment condensation, and to form the disulfide bridge under
      solid-phase conditions. The heterocyclic moiety was added in the last step of the
      synthesis to assist the preparation of libraries of new compounds with potential
      therapeutic applications.

PMID- 16953506
TI  - Perylenophthalocyanines.
AB  - The first perylenophthalocyanines have been synthesised using a Diels-Alder
      reaction between dialkylperylenes and fumaronitrile as the key step towards the
      dinitrile precursors. As expected the octaalkylperylenophthalocyanines show red
      shifted absorption spectra. They are high melting solids that do not display
      mesophase behaviour at accessible temperatures. A 3:1
      phthalocyanine/perylenophthalocyanine hybrid material, prepared by a mixed
      macrocyclisation reaction, presents an unusual board-like molecular profile. Its
      absorption maxima lie between those observed for the parent phthalocyanines and
      the symmetrical perylenophthalocyanines. The spectrum shows a characteristic
      split Q-band due to the reduced symmetry of the core. This material is non
      mesogenic but is sufficiently soluble to permit processing and characterisation.
      The (1)H NMR spectrum indicates that at least two of the appended alkyl chains
      are displaced out of the macrocycle plane and lie in its shielding region--an
      arrangement that disfavours the face-to-face packing required for mesophase
      formation.

PMID- 16953507
TI  - Terminally coordinated AsS and PS ligands.
AB  - The terminal AsS and PS complexes [(N(3)N)W(ES)] (N(3)N=N(CH(2)CH(2)NSiMe(3))(3);
      E=P (3), As (4)) were synthesised by reaction of [(N(3)N)W[triple chemical
      bond]As] and [(N(3)N)W[triple chemical bond]P], respectively, with cyclohexene
      sulfide. Both complexes present very short W--E and E--S bond lengths. The
      bonding was investigated by density functional theory (DFT) calculations using
      the fragment calculation method and natural bond orbital (NBO) analysis.
      According to the fragment analysis, in which the complexes were separated in an
      ES and a (N(3)N)W fragment, the bonding in complexes 3, 4 and [(N(3)N)W(SbS)] (5)
      is realised over a set of two sigma (1 sigma and 2 sigma) and two degenerate pi
      molecular orbitals (MOs) (1 pi and 2 pi). The 1 sigma MO is a bonding MO extended
      over the N(ax)-W-E-S core, whereas the 2 sigma MO is localised mainly on the E-S
      fragment. The 1 pi set is a E-S localised bonding molecular orbital, whereas the
      2 pi set is in phase with respect to W-E but in antiphase with respect to E-S.
      Both methods indicate bond orders around two for both the E--S and the W--E
      bonds. The polarity of the complexes was examined by Hirshfeld charge analysis.
      This shows that complexes 3 and 4 are only slightly polarised, whereas 5 is
      moderately polarised toward the sulphur. As suggested by the computational
      results, the pi system in complexes 3-5 is best described by two three-centre
      four-electron bonds.

PMID- 16953508
TI  - Hydrated dibromodioxomolybdenum(VI) supported on Zn-MCM-48 for facile oxidation
      of methane.

PMID- 16953509
TI  - Intrinsic chirality in a bent-core mesogen induced by extrinsic chiral
      structures.

PMID- 16953510
TI  - Acetylene absorption and binding in a nonporous crystal lattice.

PMID- 16953511
TI  - Experimental and theoretical investigations of the sulfite-based polyoxometalate
      cluster redox series: alpha- and beta-[Mo(18)O(54)(SO(3))(2)](4-/5-/6-).
AB  - The synthesis, isolation and structural characterization of the sulfite
      polyoxomolybdate clusters alpha-(D(3h))(C(20)H(44)N)(4){alpha
      [Mo(18)O(54)(SO(3))(2)]}CH(3)CN and beta-(D(3d))(C(20)H(44)N)(4){beta
      [Mo(18)O(54)(SO(3))(2)]}CH(3)CN is presented. Voltammetric studies in
      acetonitrile (0.1 M Hx(4)NClO(4), Hx(4)N=tetra-n-hexylammonium) reveal the
      presence of an extensive series of six one-electron reduction processes for both
      isomers. Under conditions of bulk electrolysis, the initial
      [Mo(18)O(54)(SO(3))(2)](4-/5-) and [Mo(18)O(54)(SO(3))(2)](5-/6-) processes
      produce stable [Mo(18)O(54)(SO(3))(2)](5-) and [Mo(18)O(54)(SO(3))(2)](6-)
      species, respectively, and the same reduced species may be produced by
      photochemical reduction. Spectroelectrochemical data imply that retention of
      structural form results upon reduction, so that both alpha and beta isomers are
      available at each of the 4-, 5-, and 6-redox levels. However, the alpha isomer is
      the thermodynamically favored species in both the one- and two-electron-reduced
      states, with beta-->alpha isomerization being detected in both cases on long time
      scales (days). EPR spectra also imply that increasing localization of the
      unpaired electron occurs over the alpha- and beta-[Mo(18)O(54)(SO(3))(2)](5-)
      frameworks as the temperature approaches 2 K where the EPR spectra show
      orthorhombic symmetry with different g and hyperfine values for the alpha and
      beta isomers. Theoretical studies support the observation that it is easier to
      reduce the alpha cluster than the beta form and also provide insight into the
      driving force for beta-->alpha isomerization in the reduced state. Data are
      compared with that obtained for the well studied alpha-[Mo(18)O(54)(SO(4))(2))](4
      ) sulfate cluster.

PMID- 16953512
TI  - Silver-catalyzed asymmetric synthesis of 2,3-dihydrobenzofurans: a new chiral
      synthesis of pterocarpans.
AB  - 2,3-Dihydrobenzofurans can be diastereoselectively prepared by condensation of
      aromatic aldehydes with 2,3-dihydrobenzoxasilepines under the catalysis of Ag(I)
      complexes, and in the presence of a source of fluoride ion. The application of
      this strategy by using chiral catalysts leads to a new enantioselective total
      synthesis of natural cis-pterocarpans and their trans isomers. Through this
      method, the first enantioselective total synthesis of the antifungal agent (-)
      pterocarpin was achieved. In addition, a new entry into the heteroaromatic system
      of 2,5-dihydrobenzoxepine is also presented.

PMID- 16953513
TI  - Diversity-oriented synthesis of pochonins and biological evaluation against a
      panel of kinases.
AB  - Pochonins A-F were recently characterized as six new members of the naturally
      occurring family of 14-membered resorcylic acid lactones. As there are a high
      number of ATPase and kinase inhibitors among natural resorcylic lactones, a
      library based on the pochonin scaffold, with five points of diversity, was
      prepared which includes diversity beyond that of the natural analogues. The
      library was synthesized by using solid-supported reagents amenable to automation.
      Testing the library for its inhibition against a panel of 24 kinases at 10 microM
      afforded a >14 % hit rate. These results demonstrate the potential of the
      resorcylides towards the inhibition of therapeutically relevant kinases.

PMID- 16953514
TI  - A lesson from the unusual morphology of silica mesoporous crystals: growth and
      close packing of spherical micelles with multiple twinning.

PMID- 16953515
TI  - Total synthesis and absolute stereochemistry of polygalolides A and B.

PMID- 16953516
TI  - The impact of over-the-counter simvastatin on the number of statin prescriptions
      in the United Kingdom: a view from the General Practice Research Database.
AB  - PURPOSE: The United Kingdom (UK) government changed the prescription policy of
      statins, making low-dose simvastatin (10 mg) available as an over-the-counter
      (OTC) drug in August 2004. We assessed the impact of this policy change on statin
      prescribing. METHODS: We examined all statin prescriptions in the General
      Practice Research Database (GPRD), a well-validated database of approximately 3.5
      million patients, from the first quarter of 2001 to the second quarter of 2005.
      RESULTS: From 2001, the number of statin prescriptions written for GPRD patients
      was increasing by approximately 437 prescriptions per 100,000 people per quarter
      until the time of the policy change. Over the four quarters post-policy
      implementation, however, this trend changed abruptly (p < 0.0001) with a decrease
      of 281 prescriptions per 100,000 people per quarter. This decrease was not
      restricted to prescriptions of 10 mg statins but was also observed for statin
      prescriptions of >or=20 mg. Several other cardiovascular medications displayed a
      similar trend as that observed in the number of statin prescriptions. This trend
      was not observed among non-cardiovascular control medications. CONCLUSIONS: Our
      study suggests that the policy allowing the OTC sale of 10 mg simvastatin has had
      a significant impact on statin prescriptions by general practitioners. However,
      this new policy may also be leading to less aggressive statin therapy. An
      alternative explanation for the observed decrease in statin prescriptions may be
      related to the unknown factors responsible for the overall decrease observed with
      other cardiovascular prescription drugs.

PMID- 16953517
TI  - Risk minimization practices for pregnancy prevention: understanding risk,
      selecting tools.
AB  - According to the March of Dimes, approximately 4% (1/28) of babies are born in
      the US each year with a birth defect. For the majority of birth defects the
      etiology is unknown, although chemicals, including drug exposures, probably
      account for less than 1% of all birth defects. The identification of potential
      human teratogenicity during drug development is important because drug-induced
      adverse fetal effects are potentially preventable with the application of risk
      assessment strategies and risk minimization tools and programs to minimize risk
      of pregnancy exposure while preserving access to drug benefits; risk assessment
      and risk minimization together comprise risk management. It is important that
      risk minimization programs intended to limit fetal exposure use a consistent
      approach and are tailored to the product-specific risk concerns in order to
      optimize the benefit-risk balance for a particular drug. This paper highlights
      general considerations in developing specific risk minimization programs to
      prevent fetal drug exposure including the relative advantages and disadvantages
      of each strategy.

PMID- 16953518
TI  - Pharmacists' attitudes towards the reporting of suspected adverse drug reactions
      in Norway.
AB  - BACKGROUND: In Scandinavian countries, pharmacists have not reported adverse drug
      reactions (ADRs), either due to legislative restrictions or because of lack of
      tradition. From 1 January 2005, Norwegian pharmacists have been encouraged by the
      Norwegian Medicines Agency to take a larger role in the reporting of ADRs.
      OBJECTIVE: To explore pharmacists' attitudes towards pharmacovigilance and their
      experiences with ADR reporting, to evaluate the effect of an educational
      programme and to compare these findings to the attitudes in a control group.
      METHODS: From September 2004, pharmacies in two of Norway's five health regions
      were invited to attend a 3-month ADR reporting study, and 39 pharmacies were
      recruited. One pharmacist from each pharmacy participated in a 1 day pre-study
      educational programme and a 1 day post-study evaluation meeting. Pharmacists
      involved in the study answered a questionnaire (A) regarding their attitudes to
      ADR reporting (active group). A control group answered the same questionnaire.
      One reminder was sent. The active group evaluated the study by answering
      questionnaire A once more and an evaluation questionnaire (B). Qualitative
      aspects of ADR reporting were discussed with the active group post-study.
      RESULTS: The response rate for questionnaire A was 97% (n = 158) in the active
      group, 74% (n = 184) in the control group and the response rate for questionnaire
      A and B post-study was 68% (n = 105) in the active group. Pharmacists in the
      active group had more positive attitudes to ADR reporting after taking part in
      the study than the control group (p < 0.001). Lack of time, confidence and
      knowledge of reporting rules could potentially prevent them from reporting ADRs.
      CONCLUSIONS: The pharmacists had positive attitudes towards pharmacovigilance,
      but very little experience with reporting. The educational programme clarified
      their role and increased their knowledge about the reporting requirements.

PMID- 16953519
TI  - Schizotypy, marijuana, and differential item functioning.
AB  - At least five studies report elevated schizotypy scores in cannabis users. The
      current research confirms higher schizotypy scores in regular cannabis users.
      Nevertheless, further analyses reveal that select items on the brief version of
      the Schizotypal Personality Questionnaire do not function comparably in current
      and former users. Multiple statistical approaches confirmed this problem,
      including the Mantel-Haenszel statistic, Rasch difficulty estimates, a logistic
      regression approach, the Breslow-Day (BD) statistic, and a combined decision rule
      using Mantel-Haenszel and BD together. Cannabis users appear to misinterpret at
      least one item, "I sometimes use words in unusual ways" making them more likely
      to endorse it even if they are no more schizotypal than the former users. Users
      might consider cannabis-related slang as an unusual use of words. Removing
      problematic items does not decrease the internal consistency of the measure, but
      eliminates the significant difference between current and former users. These
      results suggest that links between cannabis use and schizotypy require cautious
      interpretation and may arise from measurement problems.

PMID- 16953520
TI  - Development of a liquid chromatography/electrospray selected reaction monitoring
      method for the determination of organoarsenic species in marine and freshwater
      samples.
AB  - Cation- and anion-exchange high-performance liquid chromatography/electrospray
      selected reaction monitoring (HPLC/ES-SRM) methods were developed for the
      determination of 15 organoarsenic compounds in marine and freshwater samples. The
      results demonstrate that the developed HPLC/ES-SRM methods are powerful
      approaches for the identification of organoarsenic species in crude sample
      extracts. The detection limits, linearity as well as reproducibility for most of
      the species are comparable or even better than those measured by the
      HPLC/inductively coupled plasma mass spectrometry (ICPMS) technique. The
      qualitative analysis of the extracts shows that the developed methods allow for
      the identification of arsenicals which were not detectable by ICPMS. It was also
      demonstrated that the signal suppression caused by matrix effects means a
      significant limitation in the quantification of arsenicals by ES-SRM detection.
      This drawback is manifested especially in the case of the slightly retained
      species. The three sample-cleanup chromatographic methods including off-line size
      exclusion, on-line reversed-phase and on-line oppositely charged ion-exchange
      approaches proved to be ineffective for separation of the signal-suppressive
      matrix from the analytes. The standard addition calibration seems to be a
      suitable solution for such problems.

PMID- 16953521
TI  - Ultra-fast mass fingerprinting by high-affinity capture of peptides and proteins
      on derivatized poly(glycidyl methacrylate/divinylbenzene) for the analysis of
      serum and cell lysates.
AB  - The development of support materials in mass fingerprinting is an important task
      required for diagnostic markers in conjunction with matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The
      material-based approach, which we introduced as material-enhanced laser
      desorption/ionization (MELDI), focuses not only on different functionalities, but
      also emphasizes the morphology, i.e. porosity or particle size of the carrier
      material. As a result, it provides a quick and sensitive platform for effective
      binding of peptides and proteins out of different biofluids, e.g. serum, spinal
      fluid, urine or cell lysates, and to subsequently analyze them with MALDI-TOF MS.
      This approach includes a built-in desalting step for serum protein profiling and
      is sensitive enough to detect proteins and peptides down to 100 fmol/microL. Here
      we co-polymerized glycidyl methacrylate (GMA) with divinylbenzene (DVB) using
      thermal polymerization to yield a GMA/DVB polymer for further modifications.
      Different affinities have been created, such as immobilized metal ion affinity
      (IDA-Cu2+), reversed-phase (RP) and anion-exchanger (AX) chromatography. The
      diverse derivatizations and the dispersity of the particles created by different
      chemical synthetic approaches were confirmed by characteristic infrared (IR)
      peaks. The polymerization carried out by non-stirring yielded an average pore
      radius of 6.1 microm (macro-pores) that enhanced the binding capacity enormously
      by offering enlarged surface areas. Moreover, atomic absorption spectrometry
      (AAS) provided the metal content loaded on iminodiacetic acid (IDA) in the case
      of poly(GMA/DVB)-IDA-Cu2+. To summarize, the optimized MELDI approach is
      sensitive in its performance, extremely fast and can be adapted to robotic
      systems for routine analysis, allowing sample preparation in less than 5 min in
      contrast to the conventional surface-enhanced laser desorption/ionization (SELDI)
      methods.

PMID- 16953522
TI  - Structural determination of diterpenes from Daphne genkwa by NMR spectroscopy.
AB  - Five daphnane type diterpenes have been isolated from the chloroform soluble
      fraction of Daphne genkwa. The structure of the new compound (1) was assigned as
      5beta-hydroxyresiniferonol-6alpha,7alpha-epoxy-12beta-acetoxy-9,13,14-ortho-2E
      decenoate by extensive NMR studies.

PMID- 16953523
TI  - Rapid phase-compositional assessment of lipid-based food products by time domain
      NMR.
AB  - In food science and technology, assessment of phase-compositional behaviour of
      lipids is critical for understanding many product properties and for effective
      process control. Time Domain NMR is a rapid and easy-to-handle technique, and is
      already well appreciated as a tool for phase-compositional assessment in foods.
      The phase-compositional detail that can be obtained with the established
      methodology is limited, however. In this work, we set out to obtain more phase
      compositional details of lipids as currently feasible with the already
      established 'classical' NMR methods. We deployed a combined FID-CPMG experiment,
      and analyzed the Transversal Relaxation Decays by Deconvolution (TRDD) with semi
      empirical mathematical functions for solid, semi-solid and liquid components.
      Within the solid component, different lipid crystal polymorphs can be discerned
      in a quantitative manner, i.e. alpha, beta and beta'. The TRDD method was
      validated against established NMR SFC methods, in terms of accuracy ('trueness')
      and precision. The solid fat content (SFC) of a large collection of fat blends
      was measured by the commonly employed NMR Direct and Indirect SFC methods and a
      good correlation with the results of the TRDD was observed, thereby demonstrating
      accuracy. Furthermore, TRDD was found to be equally precise as the established
      NMR SFC methods.

PMID- 16953524
TI  - Debate rages over the "future of emergency care".

PMID- 16953525
TI  - Breaking point: Report calls for Congressional rescue of hospital emergency
      departments.

PMID- 16953526
TI  - Crossroads: Report calls for EMS standards of care.

PMID- 16953527
TI  - Growing pains: Report notes pediatric emergencies need greater emphasis.

PMID- 16953528
TI  - Too POSH for the public: are physician-owned hospitals a drain on emergency care?
      (Part II).

PMID- 16953529
TI  - Randomized clinical trial of morphine in acute abdominal pain.
AB  - STUDY OBJECTIVE: Administration of analgesia to patients with acute abdominal
      pain is controversial. We test the hypothesis that morphine given to emergency
      department (ED) patients with acute abdominal pain will reduce discomfort and
      improve clinically important diagnostic accuracy. METHODS: Pain was measured with
      a standard 0- to 100-mm visual analog scale. ED patients with acute abdominal
      pain were randomized in a double-blind fashion to 0.1 mg/kg intravenous morphine
      or placebo. The primary endpoint was the difference between the 2 study arms in
      clinically important diagnostic accuracy. Clinically important diagnostic
      accuracy was defined a priori by its complement, clinically important diagnostic
      error, using 2 independent, blinded investigators to identify any discordance
      between the provisional and final diagnoses that might adversely affect the
      patient's health status. The provisional diagnosis was provided by an ED
      attending physician, who examined the patient only once, 15 minutes after
      administration of the study agent. The final diagnosis was obtained through
      follow-up at least 6 weeks after the index ED visit. RESULTS: We randomized 160
      patients, of whom 153 patients were available for analysis, 78 patients in the
      morphine group and 75 patients in the placebo group. Baseline features were
      similar in both groups, including initial median visual analog scale scores of 98
      mm and 99 mm. The median decrease in visual analog scale score at 15 minutes was
      33 mm in the morphine group and 2 mm in the placebo group. There were 11
      instances of diagnostic discordance in each group, for a clinically important
      diagnostic accuracy of 86% (67/78) in the morphine group and 85% (64/75) in the
      placebo group. The difference in clinically important diagnostic accuracy between
      the 2 groups was 1% (95% confidence interval [CI] -11% to 12%). Analysis by
      efficacy and intention to treat yielded similar results. Kappa for interobserver
      concordance in classification of clinically important diagnostic accuracy was
      0.94 (95% CI 0.79 to 1.00). No patients required naloxone. CONCLUSION: Although
      administration of intravenous morphine to adult ED patients with acute abdominal
      pain could lead to as much as a 12% difference in diagnostic accuracy, equally
      favoring opioid or placebo, our data are most consistent with the inference that
      morphine safely provides analgesia without impairing clinically important
      diagnostic accuracy.

PMID- 16953530
TI  - Intravenous morphine plus ketorolac is superior to either drug alone for
      treatment of acute renal colic.
AB  - STUDY OBJECTIVE: To study the efficacy of intravenous ketorolac, morphine, and
      both drugs in combination in reducing pain in acute renal colic. METHODS: We
      conducted a prospective, double-blinded, randomized controlled trial in an urban,
      teaching emergency department. Patients aged 18 to 55 years and with a clinical
      diagnosis of acute renal colic and a pain rating greater than 5 on a 10-cm visual
      analogue scale or at least "moderate pain" on a 4-category verbal pain scale were
      eligible for inclusion. Exclusion criteria were contraindication to nonsteroidal
      anti-inflammatory drugs or opiates, a history of drug dependence, presence of
      peritonitis, or analgesics within 6 hours of presentation. Patients received
      either morphine 5 mg at time zero and 5 mg at 20 minutes, ketorolac 15 mg at time
      zero and 15 mg at 20 minutes, or a combination of both. Primary outcomes were
      pain reduction and the need for rescue analgesia at 40 minutes. RESULTS: Of the
      555 consecutive patients screened, 158 patients met inclusion criteria and 130
      patients were randomized during 6 months. Mean difference in change in pain score
      (visual analog scale 40 minutes minus visual analog scale 0 minutes) between
      combination group and morphine group was 1.8 cm (95% confidence interval [CI] 
      3.3 to -0.1) and, compared to the ketorolac group, was 2.2 cm (95% CI -3.7 to 
      0.5); P<.003. Patients with combination therapy were less likely to require
      rescue morphine compared to the morphine group (odds ratio 0.2; 95% CI 0.1 to
      0.7; P=.007). CONCLUSION: A combination of morphine and ketorolac offered pain
      relief superior to either drug alone and was associated with a decreased
      requirement for rescue analgesia.

PMID- 16953531
TI  - The prevalence of nontherapeutic and dangerous international normalized ratios
      among patients receiving warfarin in the emergency department.
AB  - STUDY OBJECTIVE: We determine the prevalence of nontherapeutic and coagulopathic
      international normalized ratios (INRs) among patients receiving warfarin and
      presenting to an emergency department (ED). As a secondary goal, we aim to
      determine whether a simple decision aid composed of physical examination and
      historical features could be predictive of INR greater than 5. METHODS: This was
      a prospective, observational study at 2 associated urban academic centers from
      February 2003 through May 2004, using a convenience sample of patients identified
      by direct questioning and contemporaneous medical record review in the ED as
      receiving long-term warfarin therapy. Inclusion criteria were warfarin therapy
      and self-reported compliance. Patients were enrolled by trained researchers. The
      primary outcome measure was the percentage of patients within appropriate
      therapeutic range for their condition according to accepted national guidelines.
      Descriptive statistics were used, and multivariate regression analysis was
      performed to identify associations. RESULTS: One thousand nineteen patients were
      enrolled. INR values were obtained in 77% (782/1019) of patients. Of these
      patients, 72% (95% confidence interval 67% to 76%) were outside the desired
      range. Values were less than 2 in 43% of patients and greater than 3 in 29% of
      patients. INR greater than 5 was present in 11% (86/782) of patients, and 40%
      (34/86) of these patients exhibited gross bleeding. Emergency therapy was
      administered in 12% (96/782) of patients: fresh frozen plasma in 7% of patients,
      heparin in 5% of patients. Intracranial hemorrhage was found in 12 patients, 5
      with INR greater than 3. Ischemic stroke or venous thromboembolism occurred in 51
      patients known to be receiving warfarin specifically for prevention of the event
      that occurred. Of these patients, 49% (25/51) had INR less than 2. Regression
      analysis indicated no sensitive or specific constellation of features, though 2
      factors were associated with INR greater than 5: gross hemorrhage (P=.006) and
      increasing duration of therapy (P=.047). CONCLUSION: The prevalence of
      undesirable INR in the ED is higher than in warfarin populations previously
      studied, and a significant number of nontherapeutic levels were associated with
      thromboembolism, stroke, or hemorrhage. Given the prevalence and established
      danger of subtherapeutic and supratherapeutic levels, a low threshold should be
      maintained for testing and addressing INR levels in patients receiving warfarin
      in the ED.

PMID- 16953532
TI  - Lessons learned from clinical anthrax drills: evaluation of knowledge and
      preparedness for a bioterrorist threat in Israeli emergency departments.
AB  - STUDY OBJECTIVE: Emergency department (ED) physicians and nurses are considered
      critical sentinels of a bioterrorist attack. We designed a special hospital drill
      to test EDs' response to inhalational anthrax and assess the level of
      preparedness for anthrax bioterrorism. We hypothesized that the occurrence of
      such a drill in an ED would improve the knowledge of its physicians, even those
      who had not actually participated in the drill. METHODS: We conducted 23 drills
      at all Israeli general hospitals' EDs. An actor entered the walk-in triage area,
      simulating a febrile patient with lower respiratory complaints. A chest
      radiograph with mediastinal widening, as can be seen in early anthrax disease,
      was planted in the hospital's imaging results system. Patients were instructed to
      give additional epidemiologic clues, such as having a few friends with a similar
      syndrome. Either before or after the drills, we distributed multiple choice tests
      about diagnosis and management of anthrax to the 115 senior emergency physicians
      at these hospitals. RESULTS: In 91% of EDs, a decision to admit the patient was
      made. Sixty-one percent included anthrax in the differential diagnosis and
      activated the appropriate protocols. Only 43% contacted all relevant officials.
      Average score on the anthrax tests was 58 (of 100). Physicians who were tested
      before the drill (in their institution) achieved a mean score of 54.5, whereas
      those who were tested after their ED had been exercised achieved a mean score of
      59.3. CONCLUSION: A national framework of drills on bioterrorism can help
      estimate and potentially augment national preparedness for bioterrorist threats.
      It is not, on its own, an effective educational tool. More emphasis should be
      given to formal accredited continuing medical education programs on bioterrorism,
      especially for emergency physicians and ED nurses, who will be in the front line
      of a bioterrorist attack.

PMID- 16953533
TI  - Stem cell crunch time.

PMID- 16953534
TI  - GMOs still rankle in Europe.

PMID- 16953535
TI  - Crystal clear.

PMID- 16953536
TI  - Ralph D. Freeman.

PMID- 16953538
TI  - [Effectiveness of dietary supplements in patients with osteoarthritis: the doubt
      persists].

PMID- 16953539
TI  - Abstracts of the 11th Congress of the International Society for Peritoneal
      Dialysis, 25-29 August 2006, Hong Kong.

PMID- 16953540
TI  - [Author and subject index 1999-2005].

PMID- 16953541
TI  - [Abstracts of the 7th Meeting of the French-speaking Society of Dialysis and the
      Nephrology Society, Clermont-Ferrand, France, 27-30 September 2005].

PMID- 16953543
TI  - Abstracts of the American Academy of Otolaryngology--Head and Neck Surgery
      Foundation, September 17-20, 2006, Toronto, Canada.

PMID- 16953542
TI  - Hairy cell leukemia.
AB  - Hairy cell leukemia is a rare B-cell neoplasm. When treated with either
      pentostatin or cladribine, complete and durable remissions can be secured and
      life expectancy for most patients is normal. A small minority of patients require
      alternative treatment with monoclonal antibodies or immunotoxins. Patients who
      attain a complete response to first-line treatment have the best prognosis.

PMID- 16953544
TI  - [Guidelines of the Spanish Society of Nephrology. Clinical practice guidelines
      for peritoneal dialysis].
AB  - In Spain and in each of its autonomous communities, the dialysis treatment of
      chronic renal disease stage 5 is totally covered by public health. Peritoneal
      dialysis, in any of its modalities, is established as the preferred home dialysis
      technique and is chosen by high percentage of patients as their choice in
      dialysis treatment. The Spanish Society of Nephrology has promoted a project of
      creation of performance guides in the field of peritoneal dialysis, entrusting a
      work group composed of members of the Spanish Society of Nephrology a with the
      development of these guides. The information offered is based on levels of
      evidence, opinion and clinical experience of the most relevant publications of
      the topic. In these guides, after defining the concept of << peritoneal
      dialysis>>, the obligations and responsibilities of the sanitation team of the
      peritoneal dialysis unit are determined, and protocols and performance procedures
      that try to include all the aspects that concern the patient with chronic renal
      disease in substitute treatment with this technique are developed. They propose
      prescription objectives based on available clinical evidence and, lacking this,
      on the consensus of the experts' opinions. The final aim is to improve the care
      and quality of the of the patient in peritoneal dialysis, optimizing in this way
      the survival of the patient and of the technique. In Spain, as in other
      neighbouring countries, peritoneal dialysis has an incidence and prevalence that
      is much lower than that of hemodialysis, ranging in the last evaluation by the
      Spanish Society of Nephrology between 5 and 24% in the different autonomous
      communities. The great majority of peritoneal dialysis units form part of the
      public network of the Spanish state, with special representation as a Satellite
      Unit or Concerted Center related to the public hospital of reference, on which it
      must depend.

PMID- 16953545
TI  - [About Chlamydia].

PMID- 16953546
TI  - [The cardiorenal anemia syndrome and treatment with EPO].

PMID- 16953547
TI  - [Should the Ugeskrift take in secondary publications without independent peer
      reviews?].

PMID- 16953548
TI  - [Antihypertensive agents do not eliminate the risk of apoplexy].

PMID- 16953549
TI  - ["Heredity and cancer"--a special feature issue with problems].

PMID- 16953550
TI  - [Acupuncture therapy of low back pain].

PMID- 16953551
TI  - A comparison of colorectal neoplasia screening tests: a multicentre community
      based study of the impact of consumer choice.

PMID- 16953552
TI  - The changing of the guard. Interview by Casey L. Penn.

PMID- 16953553
TI  - How did chikungunya reach the Indian Ocean?

PMID- 16953554
TI  - Abbott accused of refusing access to HIV drug.

PMID- 16953556
TI  - Findings of misconduct in science.

PMID- 16953555
TI  - Gates Foundation gives boost to AIDS vaccine discovery.

PMID- 16953557
TI  - Gene expression analysis in HBV transgenic mouse liver: a model to study early
      events related to hepatocarcinogenesis.
AB  - Hepatitis B virus (HBV) is one of the major etiological factors responsible for
      the development of hepatocellular carcinoma (HCC). We used a transgenic mouse,
      containing HBV sequences, as a model system to unravel the molecular mechanisms
      of hepatocarcinogenesis induced by HBV. We chose this animal model because it
      consistently develops liver cancer after intermediate steps that mimic the
      natural history of HBV infection in humans. In this study, we focus our attention
      on the early events leading to liver cancer. We compared the gene expression
      profile of 3-month-old transgenic mice with that of 3-month-old wild-type (wt)
      animals. In the transgenic mouse, microarray data analysis showed a total of 45
      significantly differentially expressed genes, 25 highly expressed (fold change >
      or =2; P = 0.0025), and 20 downregulated (fold change < or =0.5; P = 0.0025).
      These genes belong to several different functional categories such as the
      regulation of immunological response, transcription, intracellular calcium ion
      mobilization, regulation of cell cycle and proliferation, NF-kappab signal
      transduction cascades, and apoptosis. In particular, the upregulation of the
      antiapoptotic gene NuprI and the downregulation of the proapoptotic gene Bnip3
      were found. This observation was supported by an in vitro apoptosis assay that
      showed downregulation of apoptosis in hepatocytes of HBV transgenic mouse
      compared with wt mice treated with staurosporine. In conclusion, our experimental
      approach allowed identification of new genes modulated by HBV and showed that the
      apoptotic process was deregulated in transgenic mouse hepatocytes. These data
      shed light on one possible mechanism by which HBV induces hepatocarcinogenesis.

PMID- 16953558
TI  - Anti-HMGB1 neutralizing antibody ameliorates gut barrier dysfunction and improves
      survival after hemorrhagic shock.
AB  - Intestinal barrier dysfunction occurs following hemorrhagic shock and
      resuscitation (HS/R). High-mobility group B1 (HMGB1) has been shown to increase
      the permeability of Caco-2 human enterocyte-like epithelial monolayers in vitro.
      In this study, we found that serum concentrations of HMGB1 were higher in blood
      samples obtained from 25 trauma victims with hemorrhagic shock than in 9 normal
      volunteers. We also studied whether treatment with anti-HMGB1 antibody can
      ameliorate HS/R-induced gut barrier dysfunction in mice. Animals were shocked by
      withdrawal of blood to maintain mean arterial pressure at 25 to 30 mmHg for 2 h.
      After resuscitation with shed blood plus Ringer's lactate solution, the mice were
      treated with either anti-HMGB1 antibody or nonimmune rabbit IgG. Serum HMGB1
      concentrations were significantly higher in trauma victims than control mice.
      Treatment with anti-HMGB1 antibody improved survival at 24 h and ameliorated the
      development of ileal mucosal hyperpermeability to FITC-labeled dextran. At 24 h
      after HS/R, treatment with anti-HMGB1 antibody decreased bacterial translocation
      to mesenteric lymph nodes and was associated with lower circulating
      concentrations of IL-6 and IL-10. These data support the notion that HMGB1 is a
      mediator of HS/R-induced gut barrier dysfunction and suggest that anti-HMGB1
      antibodies warrant further evaluation as a therapeutic to ameliorate the
      morbidity of HS/R in trauma patients.

PMID- 16953559
TI  - Differentially expressed genes between early and advanced hepatocellular
      carcinoma (HCC) as a potential tool for selecting liver transplant recipients.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world.
      Liver transplantation (LT) represents a curative treatment for "small" HCC.
      Preoperative staging is critical in selecting optimal candidates for LT to
      optimize the use of this scarce resource. From December 1997 to February 2004,
      148 patients diagnosed with cirrhosis and HCC were evaluated at our center. After
      staging, the patients were listed for LT according to United Network for Organ
      Sharing (UNOS) criteria. When pretransplant liver MRIs were compared with the
      findings of the explanted livers, 8 of 35 patients (22.8%) were understaged.
      Three of the 8 patients (37.5%) had recurrence post-LT. A retrospective gene
      expression profiling study was done using microarray technology for tumor samples
      in the pretransplant hepatitis C virus (HCV)-HCC understaged patients and in a
      contemporaneous group of HCV-HCC patients that were accurately staged. Two sample
      t tests comparing the early versus advanced HCV-HCCs with respect to gene
      expression showed an important set of genes differentially expressed among the
      samples. Hierarchical clustering analysis of the gene expression profiling
      classified 93.8% of the total tumor samples and 85.7% of the understaged samples
      in concordance with the explanted pathological staging. We found a distinctive
      pattern of gene expression between early and advanced HCV-HCCs. These results
      suggest that gene expression profiling could improve the pre-LT HCC staging to
      more closely mimic the explant pathology. Whether gene expression profiling of
      HCC will be refined to the point of predicting potential metastatic biologic
      behavior to predict post-LT recurrence will require longitudinal prospective
      study of this gene array technology.

PMID- 16953560
TI  - In silico and in vivo approach to elucidate the inflammatory complexity of CD14
      deficient mice.
AB  - The inflammatory phenotype of genetically modified mice is complex, and the role
      of Gram-negative lipopolysaccharide (LPS) in acute inflammation induced by
      surgical cannulation trauma, alone or in combination with hemorrhage and
      resuscitation ("hemorrhagic shock"), is both complex and controversial. We sought
      to determine if a mathematical model of acute inflammation could elucidate both
      the phenotype of CD14-deficient (CD14(-/-)) mice--following LPS, cannulation, or
      hemorrhagic shock--and the role of LPS in trauma/hemorrhage-induced inflammation.
      A mathematical model of inflammation initially calibrated in wild-type (C57Bl/6)
      mice subjected to LPS, cannulation, and hemorrhagic shock was recalibrated in
      CD14(-/-) mice subjected to the same insults, yielding an ensemble of models that
      suggested specific differences at the cellular and molecular levels (for example,
      43-fold lower activation of leukocytes by LPS). The CD14(-/-)-specific model
      ensemble could account for complex changes in inflammatory analytes in these mice
      following LPS treatment. Model prediction of similar organ damage in CD14(-/-)
      and wild-type mice subjected to cannulation alone or with hemorrhagic shock was
      verified in vivo (similar ALT levels). These studies suggest that LPS-CD14
      responses do not cause inflammation in surgical trauma/hemorrhagic shock and
      demonstrate a novel use of combined in silico and in vivo methods to elucidate
      the complex inflammatory phenotype of genetically modified animals.

PMID- 16953561
TI  - Targeting of hepatoma cell and suppression of tumor growth by a novel 12mer
      peptide fused to superantigen TSST-1.
AB  - Hepatocellular carcinoma (HCC), one of the most common and malignant tumors
      worldwide, is unresponsive to any of the available therapies. Using intact HCC
      cells as therapeutic targets, we isolated a novel peptide, denoted HCC79
      (KSLSRHDHIHHH), from a phage display peptide library. HCC79 can bind to hepatoma
      cell membranes with high affinity and specificity. Remarkably, competitive
      binding assays demonstrated that HCC79 competed with HAb25, a specific antibody
      for HCC, in binding to hepatoma cells. The corresponding synthetic peptide did
      not inhibit tumor proliferation directly, but repressed tumor invasion
      significantly in a cell migration assay. Moreover, we explored the potential of
      the selected peptide to deliver a superantigen (SAg) to cancer cells, to attain a
      significant cell-targeting effect. When the peptide is fused to the TSST-1 SAg,
      the resulting fusion protein could bind to hepatoma cells with high affinity in
      vitro and improved the tumor inhibition effect by activating T lymphocyte cells
      in vitro and in vivo, compared with TSST-1 alone. Taken together, our results
      indicate that this peptide and its future derivatives may have the potential to
      be developed into highly specific therapeutic agents against cancer.

PMID- 16953562
TI  - Carbamylated erythropoietin reduces radiosurgically-induced brain injury.
AB  - Gamma knife radiosurgery is an attractive noninvasive treatment of brain tumors
      and vascular malformations that minimizes collateral tissue damage. However,
      exposure of normal tissue to even low-dose radiation triggers a cascade of acute
      and chronic injury and potentially significant morbidity and mortality. Because
      many irradiated patients now survive for years, identifying methods to prevent
      radiotherapy-induced collateral tissue damage is a major focus of current
      research. Erythropoietin (EPO), a cytokine produced locally by many tissues in
      response to injury, antagonizes apoptosis, reduces inflammation, and promotes
      healing. Systemic administration of recombinant EPO, widely used for treatment of
      anemia, provides robust protection from numerous insults in a variety of tissues,
      including the brain. Although irradiation injury is likely sensitive to EPO, the
      hematopoietic activity of EPO is undesirable in this setting, increasing
      erythrocyte number and predisposing to thrombosis. To avoid these potential
      adverse effects, we developed carbamylated EPO (CEPO) which does not stimulate
      the bone marrow. In this study, we show that CEPO (50 microg kg(-1)
      intraperitoneally) improves functional outcome when administered to adult rats
      just before, and then once daily for 10 d after, a necrotizing dose of radiation
      (100 Gy) to the right striatum. Immediately following irradiation, use and reflex
      movements of the contralateral forelimb to vibrissae stimulation were abnormal
      but rapidly improved in animals receiving CEPO. Moreover, histological
      examination revealed that the extent of brain necrosis after 90 days was reduced
      by approximately 50%. These findings further extend the kinds of injury for which
      administration of a tissue-protective cytokine provides benefit.

PMID- 16953564
TI  - Solution NMR and computer simulation studies of active site loop motion in
      triosephosphate isomerase.
AB  - Solution NMR spin relaxation experiments and classical MD simulations are used to
      study the dynamics of triosephosphate isomerase (TIM) in complex with glycerol 3
      phosphate (G3P). Three regions in TIM exhibit conformational transitions on the
      micros-ms time scale as detected by chemical exchange broadening effects in NMR
      spectroscopy: residue Lys 84 on helix C, located at the dimeric interface; active
      site loop 6; and helix G. The results indicate that the conformational exchange
      process affecting the residues of loop 6 is the correlated opening and closing of
      the loop. Distinct processes are responsible for the chemical exchange
      linebroadening observed in the other regions of TIM. MD simulations confirm that
      motions of individual residues within the active site loop are correlated and
      suggest that the chemical exchange processes observed for residues in helix G
      arise from transitions between 3(10)- and alpha-helical structures. The results
      of the joint NMR and MD study provide global insight into the role of
      conformational dynamic processes in the function of TIM.

PMID- 16953563
TI  - MyD88 and Src are differentially regulated in Kupffer cells of males and
      proestrus females following hypoxia.
AB  - Hypoxia produces sex dimorphic immune responses in males and proestrus females.
      Because Kupffer cells are the major source of proinflammatory cytokines, studies
      were conducted to discern IL-6 production in mouse Kupffer cells following
      hypoxia. Hypoxia enhances TLR4 expression in Kupffer cells irrespective of sex.
      However, MyD88 and Src expression in Kupffer cells decreased significantly after
      hypoxia in proestrus females, whereas Src protein expression and phosphorylation
      increased in males in concurrence with differences in IL-6 production. 17beta
      estradiol administration elevated MyD88 and Src expression in males to levels in
      normoxic proestrus females. Administration of Src inhibitor in hypoxic males
      prevented increased IL-6 production. Thus, differential regulation of MyD88 and
      Src in males and females plays an important role in sex-specific immune response
      following hypoxia.

PMID- 16953565
TI  - Increase of RNase a N-terminus polarity or C-terminus apolarity changes the two
      domains' propensity to swap and form the two dimeric conformers of the protein.
AB  - Do the polarities of the N-terminus or the apolarity of the C-terminus of bovine
      RNase A influence the relative yields of its two 3D domain-swapped dimeric
      conformers, the N-dimer and C-dimer? We have addressed this question by
      substituting Ala-4 or Ala-5 with serine (A4S and A5S mutants) or Ser-123 with
      alanine (S123A mutant) through site-directed mutagenesis. Both the polarity of
      the N-terminus and the apolarity of the C-terminus of RNase A were, therefore,
      increased. CD spectra revealed no significant differences between the secondary
      structures of the mutants and native RNase A. According to thermal denaturation
      analyses, the A4S and A5S mutants are less stable, and the S123A mutant is more
      stable than wild type RNase A. By subjecting the mutants under mild or drastic
      denaturing conditions, side-by-side with native and recombinant RNase A, to a
      thermally induced oligomerization procedure, the following results were obtained.
      (i) The N-terminal mutants showed a higher propensity, with respect to the native
      protein, to form N-dimers under mild unfolding conditions. (ii) The C-terminal
      mutant showed a higher propensity to form the C-dimer under severely unfolding
      conditions. These results are discussed in light of the relative stabilities of
      the various RNase A species under different environmental conditions, and we
      conclude that the hydrophilic or hydrophobic character of the RNase N-terminus or
      C-terminus can be an important variable governing the oligomerization of RNase A
      and possibly other proteins through the 3D domain-swapping mechanism.

PMID- 16953566
TI  - Computational study of the binding affinity and selectivity of the bacterial
      ammonium transporter AmtB.
AB  - We report results from microscopic molecular dynamics and free energy
      perturbation simulations of substrate binding and selectivity for the Escherichia
      coli high-affinity ammonium transporter AmtB. The simulation system consists of
      the protein embedded in a model membrane/water surrounding. The calculated
      absolute binding free energies for the external NH(4)(+) ions are between -5.8
      and -7.3 kcal/mol and are in close agreement with experimental data. The apparent
      pK(a) of the bound NH(4)(+) increases by more than 4 units, indicating a
      preference for binding ammonium ion and not neutral ammonia. The external binding
      site is also selective for NH(4)(+) toward monovalent metal cations by 2.4-4.4
      kcal/mol. The externally bound NH(4)(+) shows strong electrostatic interactions
      with the proximal buried Asp160, stabilized in the anionic form, whereas the
      interactions with the aromatic rings of Phe107 and Trp148, lining the binding
      cavity, are less pronounced. Simulated mutation of the highly conserved Asp160 to
      Asn reduces the pK(a) of the bound ammonium ion by approximately 7 units and
      causes loss of its binding. The calculations further predict that the substrate
      affinity of E. coli AmtB depends on the ionization state of external histidines.
      The computed free energies of hypothetical intermediate states related to
      transfer of NH(3), NH(4)(+), or H(2)O from the external binding site to the first
      position inside the internal channel pore favor permeation of the neutral species
      through the channel interior. However, the predicted change in the apparent pK(a)
      of NH(4)(+) upon translocation from the external site, Am1, to the first internal
      site, Am2, indicates that ammonium ion becomes deprotonated only when it enters
      the channel interior.

PMID- 16953568
TI  - Photoreaction cycle of the light, oxygen, and voltage domain in FKF1 determined
      by low-temperature absorption spectroscopy.
AB  - Flavin-binding Kelch repeat F-box (FKF1) protein plays important roles in the
      photoregulation of flowering in Arabidopsis. FKF1 has a light, oxygen, and
      voltage (LOV) sensing domain binding a flavin mononucleotide (FMN) as a
      chromophore noncovalently. Photoreaction of the FKF1-LOV polypeptide was studied
      by low-temperature absorption spectroscopy. Upon blue light irradiation, a ground
      state, D(450), is converted to S(390) known as a cysteinyl-flavin adduct
      intermediate in the photoreaction of phototropin. Below 150 K, bleaching of
      D(450) was much reduced and a new photoproduct, Z(370), appeared as well as
      S(390) formation. The calculated absorption spectrum for Z(370) is very similar
      to those of flavoproteins in an anion radical state. On the basis of the results
      that S(390) formation proceeds to Z(370) formation and that Z(370) formed at low
      temperatures reverts to D(450) upon temperature increase, Z(370) is concluded to
      be not an intermediate from D(450) to S(390). Z(370) is suggested to be formed
      from the biradical triplet-excited state after relaxing to the ground state with
      the FMN anion radical trapped at the low temperature, in which the SH of the
      cysteine is in the wrong position that is able to produce a radical pair but
      unable to form the cysteinyl-flavin adduct. The counter SH in the cationic
      radical state may revert to the ground state by extracting an electron from the
      unidentified amino acid residue. Interestingly, S(390) that has been thought to
      be irreversible to D(450) was revealed to revert to D(450) very slowly with a
      half-life time of 62.5 h in solution at 298 K. The photoreaction mechanism is
      discussed in reference to the calculated activation energy of the reaction
      processes.

PMID- 16953567
TI  - Structure of the DPS-like protein from Sulfolobus solfataricus reveals a
      bacterioferritin-like dimetal binding site within a DPS-like dodecameric
      assembly.
AB  - The superfamily of ferritin-like proteins has recently expanded to include a
      phylogenetically distinct class of proteins termed DPS-like (DPSL) proteins.
      Despite their distinct genetic signatures, members of this subclass share
      considerable similarity to previously recognized DPS proteins. Like DPS, these
      proteins are expressed in response to oxidative stress, form dodecameric cage
      like particles, preferentially utilize H(2)O(2) in the controlled oxidation of
      Fe(2+), and possess a short N-terminal extension implicated in stabilizing
      cellular DNA. Given these extensive similarities, the functional properties
      responsible for the preservation of the DPSL signature in the genomes of diverse
      prokaryotes have been unclear. Here, we describe the crystal structure of a DPSL
      protein from the thermoacidophilic archaeon Sulfolobus solfataricus. Although the
      overall fold of the polypeptide chain and the oligomeric state of this protein
      are indistinguishable from those of authentic DPS proteins, several important
      differences are observed. First, rather than a ferroxidase site at the subunit
      interface, as is observed in all other DPS proteins, the ferroxidase site in
      SsDPSL is buried within the four-helix bundle, similar to bacterioferritin.
      Second, the structure reveals a channel leading from the exterior surface of
      SsDPSL to the bacterioferritin-like dimetal binding site, possibly allowing
      divalent cations and/or H(2)O(2) to access the active site. Third, a pair of
      cysteine residues unique to DPSL proteins is found adjacent to the dimetal
      binding site juxtaposed between the exterior surface of the protein and the
      active site channel. The cysteine residues in this thioferritin motif may play a
      redox active role, possibly serving to recycle iron at the ferroxidase center.

PMID- 16953569
TI  - Trinucleosome compaction studied by fluorescence energy transfer and scanning
      force microscopy.
AB  - The effect of the salt concentration, linker histone H1, and histone acetylation
      on the structure of trinucleosomes reconstituted on a 608 bp DNA containing one
      centered nucleosome positioning signal was studied. Fluorescence resonance energy
      transfer (FRET) in solution and scanning force microscopy (SFM) measurements in
      liquid were done on the same samples. The distance between the DNA ends decreases
      under the effect of an increasing salt concentration and also by the
      incorporation of the H1 linker histone. A decrease of internucleosomal center-to
      center (cc) distances by H1 was observed that was limited to a minimal value of
      about 20 nm. The distribution of the angle formed between consecutive nucleosomes
      was narrowed by H1. The effect of acetylation of all histones leads to
      decompaction, measured as an increased distance between the DNA ends, and also
      increased the internucleosomal distances. Selective acetylation of histone H4,
      however, compacts the structure as measured by FRET.

PMID- 16953570
TI  - Substrate-dependent unfolding of the energy coupling motif of a membrane
      transport protein determined by double electron-electron resonance.
AB  - BtuB is a TonB-dependent transport protein that binds and carries vitamin B(12)
      across the outer membrane of Gram negative bacteria such as Escherichia coli.
      Previous work has demonstrated that the Ton box, a highly conserved segment near
      the N-terminus of the protein, undergoes an order-to-disorder transition upon the
      binding of substrate. Here, we incorporate pairs of nitroxide spin labels into
      membrane reconstituted BtuB and utilize a four-pulse double electron-electron
      resonance (DEER) experiment to measure distances between the Ton box and the
      periplasmic surface of the transporter with and without substrate. During
      reconstitution, the labeled membrane protein was diluted with wild-type protein,
      which significantly reduced the intermolecular electron spin-spin relaxation rate
      and increased the DEER signal-to-noise ratio. In the absence of substrate, each
      spin pair gives rise to a single distribution of distances that is consistent
      with the crystal structure obtained for BtuB; however, distances that are much
      longer are found in the presence of substrate, and the data are consistent with
      the existence of an equilibrium between folded and unfolded states of the Ton
      box. From these distances, a model for the position of the Ton box was
      constructed, and it indicates that the N-terminal end of the Ton box extends
      approximately 20 to 30 A into the periplasm upon the addition of substrate. We
      propose that this substrate-induced extension provides the signal that initiates
      interactions between BtuB and the inner membrane protein TonB.

PMID- 16953571
TI  - Lipid headgroup superlattice modulates the activity of surface-acting cholesterol
      oxidase in ternary phospholipid/cholesterol bilayers.
AB  - The relationship between the molecular organization of lipid headgroups and the
      activity of surface-acting enzyme was examined using a bacterial cholesterol
      oxidase (COD) as a model. The initial rate of cholesterol oxidation by COD in
      fluid state 1-palmitoyl-2-oleoyl-phosphatidylethanolamine/1-palmitoyl-2-oleoyl
      phosphatidylcholine/cholesterol (POPE/POPC/CHOL) bilayers was measured as a
      function of POPE-to-phospholipid mole ratio (X(PE)) and cholesterol-to-lipid mole
      ratio (X(CHOL)) at 37 degrees C. At X(PE) = 0, the COD activity changed abruptly
      at X(CHOL) approximately 0.40, whereas major activity peaks were detected at
      X(PE) approximately 0.18, 0.32, 0.50, 0.64, and 0.73 when X(CHOL) was fixed to
      0.33 or 0.40. At a fixed X(CHOL) of 0.50, the COD activity increased
      progressively with PE content and exhibited small peaks or kinks at X(PE)
      approximately 0.40, 0.50, 0.58, 0.69, and 0.81. When X(PE) and X(CHOL) were
      systematically varied within a narrow 2-D lipid composition window, an onset of
      COD activity at X(CHOL) approximately 0.40 and the elimination of the activity
      peak at X(PE) approximately 0.64 for X(CHOL) >0.40 were clearly observed. Except
      for X(PE) approximately 0.40 and 0.58, the observed critical PE mole ratios agree
      closely (+/-0.03) with those predicted by a headgroup superlattice model
      (Virtanen, J.A., et al. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 4964-4969;
      Cannon, B., et al. (2006) J. Phys. Chem. B 110, 6339-6350), which proposes that
      lipids with headgroups of different sizes tend to adopt regular, superlattice
      like distributions at discrete and predictable compositions in fluid lipid
      bilayers. Our results indicate that headgroup superlattice domains exist in lipid
      bilayers and that they may play a crucial role in modulating the activity of
      enzymes acting on the cell membrane surface.

PMID- 16953572
TI  - Conformational distributions of protease-serpin complexes: a partially
      translocated complex.
AB  - Serpins regulate serine proteases by forming metastable covalent complexes with
      their targets. The protease docks with the serpin and cleaves the serpin's
      reactive center loop (RCL) forming an acylenzyme intermediate. Cleavage triggers
      insertion of the RCL into beta sheet A, translocating the attached protease
      approximately 70 A and disrupting the protease active site, trapping the
      acylenzyme intermediate. Using single-pair Forster resonance energy transfer
      (spFRET), we have measured the conformational distributions of trypsin and
      alpha(1)-proteinase inhibitor (alpha(1)PI) covalent complexes. Bovine trypsin
      (BTryp) complexes display a single set of conformations consistent with the full
      translocation of BTryp (E(full)I*). However, the range of spFRET efficiencies is
      large, suggesting that the region around the trypsin label is mobile. Most
      complexes between alpha(1)PI variants and the more stable rat trypsin (RTryp)
      also show a single set of conformations, but the conformational distribution is
      narrower, indicating less disruption of RTryp. Surprisingly, RTryp complexes
      containing alpha(1)PI labeled at Cys232 with a cationic fluorophore display two
      equally populated conformations, E(full)I* and a conformation in which RTryp is
      only partially translocated (E(part)I*). Destabilizing the RTryp active site, by
      substituting Ala for Ile16, increases the E(full)I* population. Thus,
      interactions between anionic RTryp and cationic dyes likely exert a restraining
      force on alpha(1)PI, increasing the energy needed to translocate trypsin, and
      this force can be counteracted by active site destabilization. These results
      highlight the role of protease stability in determining the conformational
      distributions of protease-serpin covalent complexes and show that full
      translocation is not required for the formation of metastable complexes.

PMID- 16953573
TI  - Structural and chemical changes of the P(M) intermediate of paracoccus
      denitrificans cytochrome c oxidase revealed by IR spectroscopy with labeled
      tyrosines and histidine.
AB  - Structural and chemical changes in the P(M) intermediate of Paracoccus
      denitrificans cytochrome c oxidase have been investigated by attenuated total
      reflection-Fourier transform infrared spectroscopy. Prior studies of P(M) minus
      oxidized (O) IR difference spectra of unlabeled, universally (15)N-labeled and
      ring-d(4)-tyrosine-labeled proteins (Iwaki, M., Puustinen, A., Wikstrom, M., and
      Rich, P. R. (2004) Biochemistry 43, 14370-14378). provided a basis for band
      assignments to changes in metal centers and the covalently linked His-Tyr ligand
      of Cu(B) and highlighted a structural alteration of the protonated Glu278 in the
      P(M) intermediate. This work has been extended to equivalent measurements on
      enzymes with (13)C(9)(15)N-labeled and ring-(13)C(6)-labeled tyrosine and with
      (13)C(6)(15)N(3)-labeled histidine. Histidine labeling allows the assignment of
      troughs at 1104 and 973 cm(-1) in reduced minus O spectra to histidine changes,
      whereas tyrosine labeling moves otherwise obscured tyrosine bandshifts to 1454
      1437 and 1287-1284 cm(-1). P(M) minus O spectra reveal bands at 1506, 1311, and
      1094 cm(-1) in the oxidized state that are replaced by a band at 1519 cm(-1) in
      P(M). These bands shift with both tyrosine- and histidine-labeling, providing
      evidence for their assignment to the covalent His-Tyr and for its chemical change
      in P(M). Comparisons of isotope effects on the amide I regions in P(M) minus O
      spectra demonstrate that amide carbonyl bonds of tyrosine and histidine are major
      contributors. This suggests a structural alteration in P(M) that is centered on
      the His276-Pro277-Glu278-Val279-Tyr280 pentapeptide formed by the His-Tyr
      covalent linkage. This structural change is proposed to mediate the perturbation
      of the IR band of the protonated Glu278 headgroup.

PMID- 16953574
TI  - Computational analysis of the mode of binding of 8-oxoguanine to
      formamidopyrimidine-DNA glycosylase.
AB  - 8-Oxoguanine (8OG) is the most prevalent form of oxidative DNA damage. In
      bacteria, 8OG is excised by formamidopyrimidine glycosylase (Fpg) as the initial
      step in base excision repair. To efficiently excise this lesion, Fpg must
      discriminate between 8OG and an excess of guanine in duplex DNA. In this study,
      we explore the structural basis underlying this high degree of selectivity. Two
      structures have been reported in which Fpg is bound to DNA, differing with
      respect to the position of the lesion in the active site, one structure showing
      8OG bound in the syn conformation and the other in the anti conformation.
      Remarkably, the results of our all-atom simulations are consistent with both
      structures. The syn conformation observed in the crystallographic structure of
      Fpg obtained from Bacillus stearothermophilus is stabilized through interaction
      with E77, a nonconserved residue. Replacement of E77 with Ser, creating the Fpg
      sequence found in Escherichia coli and other bacteria, results in preferred
      binding of 8OG in the anti conformation. Our calculations provide novel insights
      into the roles of active site residues in binding and recognition of 8OG by Fpg.

PMID- 16953576
TI  - Loopless Rop: structure and dynamics of an engineered homotetrameric variant of
      the repressor of primer protein.
AB  - The repressor of primer (Rop) protein has become a steady source of surprises
      concerning the relationship between the sequences and the structures of several
      of its mutants and variants. Here we add another piece to the puzzle of Rop by
      showing that an engineered deletion mutant of the protein (corresponding to a
      deletion of residues 30-34 of the wild-type protein and designed to restore the
      heptad periodicity at the turn region) results in a complete reorganization of
      the bundle which is converted from a homodimer to a homotetramer. In contrast
      (and as previously shown), a two-residue insertion, which also restores the
      heptad periodicity, is essentially identical with wild-type Rop. The new deletion
      mutant structure is a canonical, left-handed, all-antiparallel bundle with a
      completely different hydrophobic core and distinct surface properties. The
      structure agrees and qualitatively explains the results from functional,
      thermodynamic, and kinetic studies which indicated that this deletion mutant is a
      biologically inactive hyperstable homotetramer. Additional insight into the
      stability and dynamics of the mutant structure has been obtained from extensive
      molecular dynamics simulations in explicit water and with full treatment of
      electrostatics.

PMID- 16953575
TI  - Acceptor substrate selectivity and kinetic mechanism of Bacillus subtilis TagA.
AB  - Wall teichoic acids (WTAs) are anionic polymers that coat the cell walls of Gram
      positive bacteria. Because they are essential for survival or virulence in many
      organisms, the enzymes involved in the biosynthesis of WTAs are attractive
      antibiotic targets. The first committed step in the WTA biosynthetic pathway in
      Bacillus subtilis is catalyzed by TagA, which transfers N-acetylmannosamine
      (ManNAc) to the C4 hydroxyl of a membrane-anchored N-acetylglucosaminyl
      diphospholipid (GlcNAc-pp-undecaprenyl, lipid I) to make ManNAc-beta-(1,4)-GlcNAc
      pp-undecaprenyl (lipid II). We have previously shown that TagA utilizes an
      alternative substrate containing a saturated C(13)H(27) lipid chain. Here we use
      unnatural substrates and products to establish the lipid preferences of the
      enzyme and to characterize the kinetic mechanism. We report that TagA is a metal
      ion-independent glycosyltransferase that follows a steady-state ordered Bi-Bi
      mechanism in which UDP-ManNAc binds first and UDP is released last. TagA shares
      homology with a large family of bacterial glycosyltransferases, and the work
      described here should facilitate structural analysis of the enzyme in complex
      with its substrates.

PMID- 16953577
TI  - Identification of the residues involved in the unique serine specificity of
      Caenorhabditis elegans mitochondrial EF-Tu2.
AB  - In canonical translation systems, the single elongation factor Tu (EF-Tu)
      recognizes all elongator tRNAs. However, in Caenorhabditis elegans mitochondria,
      two distinct EF-Tu species, EF-Tu1 and EF-Tu2, recognize 20 species of T armless
      tRNA and two species of D armless tRNA(Ser), respectively. We previously reported
      that C. elegans mitochondrial EF-Tu2 specifically recognizes the serine moiety of
      serylated-tRNA. In this study, to identify the critical residues for the serine
      specificity in EF-Tu2, several residues in the amino acid binding pocket of
      bacterial EF-Tu were systematically replaced with corresponding EF-Tu2 residues,
      and the mutants were analyzed for their specificity for esterified amino acids
      attached to tRNAs. In this way, we obtained a bacterial EF-Tu mutant that
      acquired serine specificity after the introduction of 10 EF-Tu2 residues into its
      amino acid binding pocket. C. elegans EF-Tu2 mutants lacking serine specificity
      were also created by replacing seven or eight residues with bacterial residues.
      Further stressing the importance of these residues, we found that they are almost
      conserved in EF-Tu2 sequences of closely related nematodes. Thus, these three
      approaches reveal the critical residues essential for the unique serine
      specificity of C. elegans mitochondrial EF-Tu2.

PMID- 16953578
TI  - Biochemical and thermodynamic characterization of compounds that bind to RNA
      hairpin loops: toward an understanding of selectivity.
AB  - Elucidation of the molecular forces governing small molecule-RNA binding is
      paramount to the progress of rational design strategies. The extensive
      characterization of the aminoglycoside-16S rRNA A-site interaction has deepened
      our understanding of how aminoglycosides bind to their target and exert their
      antimicrobial effects. However, to date no other RNA binding compounds have
      undergone such rigorous evaluation, and in general the origins of small molecule
      RNA binding remain a mystery. We recently reported the identification of small
      molecules, dimers of 2-deoxystreptamine, which are able to bind selectively to
      RNA tetraloops and octaloops, respectively [Thomas, Liu, and Hergenrother (2005)
      J. Am. Chem. Soc. 127, 12434-12435]. Described herein is the biochemical and
      biophysical characterization of the RNA binding properties of the most selective
      compound, B-12, as well as closely related analogues. These studies further
      substantiate that B-12 is indeed selective for RNA octaloop sequences and
      indicate that the origin of this selectivity may lie in B-12's unusual binding
      mode, in which entropic factors are major contributors to the overall binding
      energy. In fact, isothermal titration calorimetry (ITC) experiments indicate that
      the binding of B-12 and most of its analogues is associated with a strong
      entropic contribution to the total binding energy. This is in stark contrast to
      the aminoglycosides, for which favorable enthalpy typically provides the driving
      force for binding. These studies are the first to examine small molecule-RNA
      hairpin loop binding in detail and are a necessary step toward the design of
      compounds that are specific binders for a given RNA sequence.

PMID- 16953579
TI  - Two-dimensional solid-state NMR reveals two topologies of sarcolipin in oriented
      lipid bilayers.
AB  - Sarcolipin (SLN), a 31 amino acid integral membrane protein, regulates SERCA1a
      and SERCA2a, two isoforms of the sarco(endo)plasmic Ca-ATPase, by lowering their
      apparent Ca(2+) affinity and thereby enabling muscle relaxation. SLN is expressed
      in both fast-twitch and slow-twitch muscle fibers with significant expression
      levels also found in the cardiac muscle. SLN shares approximately 30% identity
      with the transmembrane domain of phospholamban (PLN), and recent solution NMR
      studies carried out in detergent micelles indicate that the two polypeptides bind
      to SERCA in a similar manner. Previous 1D solid-state NMR experiments on
      selectively (15)N-labeled sites showed that SLN crosses the lipid bilayer with an
      orientation nearly parallel to the bilayer normal. With a view toward the
      characterization of SLN structure and its interactions with both lipids and
      SERCA, herein we report our initial structural and topological assignments of SLN
      in mechanically oriented DOPC/DOPE lipid bilayers as mapped by 2D (15)N PISEMA
      experiments. The PISEMA spectra obtained on uniformly (15)N-labeled protein as
      well as (15)N-Leu, (15)N-Ile and (15)N-Val map the secondary structure of SLN
      and, simultaneously, reveal that SLN exists in two distinct topologies. Both the
      major and the minor populations assume an orientation with the helix axis tilted
      by approximately 23 degrees with respect to the lipid bilayer normal, but vary in
      the rotation angle about the helix axis by approximately 5 degrees . The
      existence of the multiple populations in model membranes may be a significant
      requirement for SLN interaction with SERCA.

PMID- 16953580
TI  - Calcium-triggered membrane interaction of the alpha-synuclein acidic tail.
AB  - Alpha-synuclein (alpha-syn) is a 140-residue protein that aggregates in
      intraneuronal inclusions called Lewy bodies in Parkinson's disease (PD). It is
      composed of an N-terminal domain with a propensity to bind lipids and a C
      terminal domain rich in acidic residues (the acidic tail). The objective of this
      study was to examine the effect of Ca(2+) on the acidic tail conformation in
      lipid-bound alpha-syn. We exploit the extreme sensitivity of the band III
      fluorescence emission peak of the pyrene fluorophore to the polarity of its
      microenvironment to monitor subtle conformational response of the alpha-syn
      acidic tail to Ca(2+). Using recombinant human alpha-syn bearing a pyrene to
      probe either the N-terminal domain or the acidic tail, we noted that lipid
      binding resulted in an increase in band III emission intensity in the pyrene
      probe tagging the N-terminal domain but not that in the acidic tail. This
      suggests that the protein is anchored to the lipid surface via the N-terminal
      domain. However, addition of Ca(2+) caused an increase in band III emission
      intensity in the pyrene tagging the acidic tail, with a corresponding increased
      susceptibility to quenching by quenchers located in the lipid milieu, indicative
      of lipid interaction of this domain. Taken together with the increased beta-sheet
      content of membrane-associated alpha-syn in the presence of Ca(2+), we propose a
      model wherein initial lipid interaction occurs via the N-terminal domain,
      followed by a Ca(2+)-triggered membrane association of the acidic tail as a
      potential mechanism leading to alpha-syn aggregation. These observations have
      direct implications in the role of age-related oxidative stress and the attendant
      cellular Ca(2+) dysregulation as critical factors in alpha-syn aggregation in PD.

PMID- 16953581
TI  - Prediction of glycolipid-binding domains from the amino acid sequence of lipid
      raft-associated proteins: application to HpaA, a protein involved in the adhesion
      of Helicobacter pylori to gastrointestinal cells.
AB  - Protein-glycolipid interactions mediate the attachment of various pathogens to
      the host cell surface as well as the association of numerous cellular proteins
      with lipid rafts. Thus, it is of primary importance to identify the protein
      domains involved in glycolipid recognition. Using structure similarity searches,
      we could identify a common glycolipid-binding domain in the three-dimensional
      structure of several proteins known to interact with lipid rafts. Yet the three
      dimensional structure of most raft-targeted proteins is still unknown. In the
      present study, we have identified a glycolipid-binding domain in the amino acid
      sequence of a bacterial adhesin (Helicobacter pylori adhesin A, HpaA). The
      prediction was based on the major properties of the glycolipid-binding domains
      previously characterized by structural searches. A short (15-mer) synthetic
      peptide corresponding to this putative glycolipid-binding domain was synthesized,
      and we studied its interaction with glycolipid monolayers at the air-water
      interface. The synthetic HpaA peptide recognized LacCer but not Gb3. This
      glycolipid specificity was in line with that of the whole bacterium. Molecular
      modeling studies gave some insights into this high selectivity of interaction. It
      also suggested that Phe147 in HpaA played a key role in LacCer recognition,
      through sugar-aromatic CH-pi stacking interactions with the hydrophobic side of
      the galactose ring of LacCer. Correspondingly, the replacement of Phe147 with Ala
      strongly affected LacCer recognition, whereas substitution with Trp did not. Our
      method could be used to identify glycolipid-binding domains in microbial and
      cellular proteins interacting with lipid shells, rafts, and other specialized
      membrane microdomains.

PMID- 16953582
TI  - Inhibitor discovery targeting the intermediate structure of beta-amyloid peptide
      on the conformational transition pathway: implications in the aggregation
      mechanism of beta-amyloid peptide.
AB  - Abeta peptides cleaved from the amyloid precursor protein are the main components
      of senile plaques in Alzheimer's disease. Abeta peptides adopt a conformation
      mixture of random coil, beta-sheet, and alpha-helix in solution, which makes it
      difficult to design inhibitors based on the 3D structures of Abeta peptides. By
      targeting the C-terminal beta-sheet region of an Abeta intermediate structure
      extracted from molecular dynamics simulations of Abeta conformational transition,
      a new inhibitor that abolishes Abeta fibrillation was discovered using virtual
      screening in conjunction with thioflavin T fluorescence assay and atomic force
      microscopy determination. Circular dichroism spectroscopy demonstrated that the
      binding of the inhibitor increased the beta-sheet content of Abeta peptides
      either by stabilizing the C-terminal beta-sheet conformation or by inducing the
      intermolecular beta-sheet formation. It was proposed that the inhibitor prevented
      fibrillation by blocking interstrand hydrogen bond formation of the pleated beta
      sheet structure commonly found in amyloid fibrils. The study not only provided a
      strategy for inhibitor design based on the flexible structures of amyloid
      peptides but also revealed some clues to understanding the molecular events
      involved in Abeta aggregation.

PMID- 16953583
TI  - Thermodynamics of binding of a low-molecular-weight CD4 mimetic to HIV-1 gp120.
AB  - NBD-556 and the chemically and structurally similar NBD-557 are two low-molecular
      weight compounds that reportedly block the interaction between the HIV-1 envelope
      glycoprotein gp120 and its receptor, CD4. NBD-556 binds to gp120 with a binding
      affinity of 2.7 x 10(5) M(-1) (K(d) = 3.7 muM) in a process characterized by a
      large favorable change in enthalpy partially compensated by a large unfavorable
      entropy change, a thermodynamic signature similar to that observed for binding of
      sCD4 to gp120. NBD-556 binding is associated with a large structuring of the
      gp120 molecule, as also demonstrated by CD spectroscopy. NBD-556, like CD4,
      activates the binding of gp120 to the HIV-1 coreceptor, CCR5, and to the 17b
      monoclonal antibody, which recognizes the coreceptor binding site of gp120. NBD
      556 stimulates HIV-1 infection of CD4-negative, CCR5-expressing cells. The
      thermodynamic signature of the binding of NBD-556 to gp120 is very different from
      that of another viral entry inhibitor, BMS-378806. Whereas NBD-556 binds gp120
      with a large favorable enthalpy and compensating unfavorable entropy changes, BMS
      378806 does so with a small binding enthalpy change in a mostly entropy-driven
      process. NBD-556 is a competitive inhibitor of sCD4 and elicits a similar
      structuring of the coreceptor binding site, whereas BMS-378806 does not compete
      with sCD4 and does not induce coreceptor binding. These studies demonstrate that
      low-molecular-weight compounds can induce conformational changes in the HIV-1
      gp120 glycoprotein similar to those observed upon CD4 binding, revealing distinct
      strategies for inhibiting the function of the HIV-1 gp120 envelope glycoprotein.
      Furthermore, competitive and noncompetitive compounds have characteristic
      thermodynamic signatures that can be used to guide the design of more potent and
      effective viral entry inhibitors.

PMID- 16953584
TI  - Truncation of a cross-linked GCN4-p1 coiled coil leads to ultrafast folding.
AB  - Structural perturbation has been extensively used in protein folding studies
      because it yields valuable conformational information regarding the folding
      process. Here we have used N-terminal truncation on a cross-linked variant of the
      GCN4-p1 leucine zipper, aiming to develop a better understanding of the folding
      mechanism of the coiled-coil motif. Our results indicate that removing the first
      heptad repeat in this cross-linked GCN4-p1 coiled coil significantly decreases
      the folding free energy barrier and results in a maximum folding rate of (2.0 +/-
      0.3 micros)(-1), which is approximately 50 times faster than that of the full
      length protein. Therefore, these results suggest that a set of native or
      nativelike tertiary interactions, distributed throughout the entire sequence,
      collectively stabilize the folding transition state of the GCN4-p1 coiled coil.
      While stable subdomains or triggering sequences have been shown to be critical to
      the stability of GCN4 coiled coils, our results suggest that the folding of such
      a subdomain does not seem to dictate the overall folding kinetics.

PMID- 16953585
TI  - Activation of phospholipase Cepsilon by free fatty acids and cross talk with
      phospholipase D and phospholipase A2.
AB  - This paper uses phospholipase Cepsilon as a model to demonstrate that lipids can
      act as ligands to bind to specific motifs and regulate protein activity via
      allosteric effects. Phospholipids such as phosphatidic acid and free fatty acids
      such as arachidonate are potent activators of PLCepsilon, increasing the rate of
      PI hydrolysis by 8-fold and 50-fold, respectively. The mechanism appears to be a
      reduction of K(m), as the substrate dependence curve is shifted to the left and
      K(m) is reduced 10-fold. The regulation of PLCepsilon by lipids appears to be
      physiologic, as reconstitution or cotransfection of either cPLA(2) or PLD with
      PLCepsilon leads to activation of phosphodiesterase activity. Additionally, TSA
      201 cells transfected with PLCepsilon and fed arachidonic acid complexed with BSA
      had increased (4-5-fold) hydrolysis of polyphosphoinositides. This study
      demonstrates the ability of lipids to act as potent and direct mediators of
      protein function and identifies cross talk between different classes of
      phospholipase (PLD and PLA(2) with PLC) mediated via lipid products.

PMID- 16953586
TI  - Induced chirality of the light-harvesting carotenoid salinixanthin and its
      interaction with the retinal of xanthorhodopsin.
AB  - In xanthorhodopsin, a retinal protein-carotenoid complex of Salinibacter ruber,
      the carotenoid salinixanthin functions as a light-harvesting antenna in supplying
      additional excitation energy for retinal isomerization and proton transport.
      Another retinal protein, archaerhodopsin, has been shown to contain a carotenoid,
      bacterioruberin, but without an antenna function. We report here that the binding
      site confers a chiral geometry on salinixanthin in xanthorhodopsin and confirm
      that the same is true for bacterioruberin in archaerhodopsin. Cell membranes
      containing these rhodopsins exhibit CD spectra with sharp positive bands in the
      visible region where the carotenoids absorb, and in the case of xanthorhodopsin a
      negative band at 536 nm, as well as bands in the UV region. The carotenoid in
      ethanol has very weak optical activity in the visible region of the spectrum.
      Denaturation of the opsin upon deprotonation of the Schiff base at pH 12.5
      eliminates the induced CD bands in both proteins. In one of these proteins, but
      not in the other, the carotenoid binding site depends entirely on the retinal.
      Hydrolysis of the retinal Schiff base of xanthorhodopsin with hydroxylamine
      eliminates the induced CD bands of salinixanthin. In contrast, hydrolysis of the
      Schiff base in archaerhodopsin does not abolish the CD bands of bacterioruberin.
      Thus, consistent with its antenna function, the carotenoid binding site interacts
      closely with the retinal only in xanthorhodopsin, and this interaction is the
      major source of the CD bands. In this protein, protonation of the counterion with
      a decrease in pH from 8 to 5 causes significant changes in the CD spectrum. The
      observed spectral features suggest that binding of salinixanthin in
      xanthorhodopsin involves the cyclohexenone ring of the carotenoid and its
      conformational heterogeneity is restricted.

PMID- 16953587
TI  - Further enhancement of the thermostability of Hydrogenobacter thermophilus
      cytochrome c552.
AB  - Thermophile Hydrogenobacter thermophilus cytochrome c(552) (HT) is a stable
      protein with denaturation temperatures (T(m)) of 109.8 and 129.7 degrees C for
      the oxidized and reduced forms, respectively [Uchiyama, S., Ohshima, A.,
      Nakamura, S., Hasegawa, J., Terui, N., Takayama, S. J., Yamamoto, Y., Sambongi,
      Y., and Kobayashi, Y. (2004) J. Am. Chem. Soc. 126, 14684-14685]. The removal of
      a single hydroxyl group from the hydrophobic core of HT, through the replacement
      of a Tyr by Phe, resulted in further elevation of the T(m) value of the oxidized
      form by approximately 6 degrees C, the T(m) value of the reduced one remaining
      essentially unaltered. As a result, the redox potential of the mutant with higher
      stability in the oxidized form exhibited a negative shift of approximately 20 mV
      relative to that of wild-type HT in an enthalpic manner. These findings indicated
      that the redox function of a protein can be enthalpically regulated through the
      stability of the oxidized form by altering the contextual stereochemical packing
      of hydrophobic residues in the protein interior using protein engineering.

PMID- 16953588
TI  - Enzyme deactivation due to metal-ion dissociation during turnover of the cobalt
      beta-lactamase catalyzed hydrolysis of beta-lactams.
AB  - Metallo-beta-lactamases are native zinc enzymes that catalyze the hydrolysis of
      beta-lactam antibiotics but are also able to function with cobalt (II) and
      require one or two metal ions for catalytic activity. The kinetics of the
      hydrolysis of benzylpenicillin catalyzed by cobalt substituted beta-lactamase
      from Bacillus cereus (BcII) are biphasic. The dependence of enzyme activity on pH
      and metal-ion concentration indicates that only the di-cobalt enzyme is
      catalytically active. A mono-cobalt enzyme species is formed during the catalytic
      cycle, which is virtually inactive and requires the association of another cobalt
      ion for turnover. Two intermediates with different metal to enzyme
      stoichiometries are formed on a branched reaction pathway. The di-cobalt enzyme
      intermediate is responsible for the direct catalytic route, which is pH
      independent between 5.5 and 9.5 but is also able to slowly lose one bound cobalt
      ion via the branching route to give the mono-cobalt inactive enzyme intermediate.
      This inactivation pathway of metal-ion dissociation occurs by both an acid
      catalyzed and a pH-independent reaction, which is dependent on the presence of an
      enzyme residue of pK(a) = 8.9 +/- 0.1 in its protonated form and shows a large
      kinetic solvent isotope effect (H(2)O/D(2)O) of 5.2 +/- 0.5, indicative of a rate
      limiting proton transfer. The pseudo first-order rate constant to regenerate the
      di-cobalt beta-lactamase from the mono-cobalt enzyme intermediate has a first
      order dependence on cobalt-ion concentration in the pH range 5.5-9.5. The second
      order rate constant for metal-ion association is dependent on two groups of pK(a)
      6.32 +/- 0.1 and 7.47 +/- 0.1 being in their deprotonated basic forms and one
      group of pK(a) 9.48 +/- 0.1 being in its protonated form.

PMID- 16953589
TI  - Solvent-accessible cysteines in human cystathionine beta-synthase: crucial role
      of cysteine 431 in S-adenosyl-L-methionine binding.
AB  - Cystathionine beta-synthase (CBS) is a tetrameric heme protein that catalyzes the
      PLP-dependent condensation of serine and homocysteine to cystathionine. CBS
      occupies a crucial regulatory position between the methionine cycle and
      transsulfuration. Human CBS contains 11 cysteine residues that are highly
      conserved in mammals but completely absent in the yeast enzyme, which catalyzes
      an identical reaction, suggesting a possible regulatory role for some of these
      residues. In this report, we demonstrate that in both the presence and absence of
      the CBS allosteric regulator S-adenosyl-l-methionine (AdoMet), only C15 and C431
      of human CBS are solvent accessible. Mutagenesis of C15 to serine did not affect
      catalysis or AdoMet activation but significantly reduced aggregation of the
      purified enzyme in vitro. Mutagenesis of C431 resulted in a constitutively
      activated form of CBS that could not be further activated by either AdoMet or
      thermal activation. We and others have previously reported a number of C-terminal
      CBS point mutations that result in a decreased or abolished response to AdoMet.
      In contrast to all of these previously investigated CBS mutants, the C431 mutant
      form of CBS was unable to bind AdoMet, indicating that either this residue is
      directly involved in AdoMet binding or its absence induces a conformational
      change that destroys the integrity of the binding site for this regulatory
      ligand.

PMID- 16953590
TI  - Insights into the catalytic mechanisms of phenylalanine and tryptophan
      hydroxylase from kinetic isotope effects on aromatic hydroxylation.
AB  - Phenylalanine hydroxylase (PheH) and tryptophan hydroxylase (TrpH) catalyze the
      aromatic hydroxylation of phenylalanine and tryptophan, forming tyrosine and 5
      hydroxytryptophan, respectively. The reactions of PheH and TrpH have been
      investigated with [4-(2)H]-, [3,5-(2)H(2)]-, and (2)H(5)-phenylalanine as
      substrates. All (D)k(cat) values are normal with Delta117PheH, the catalytic core
      of rat phenylalanine hydroxylase, ranging from 1.12-1.41. In contrast, for
      Delta117PheH V379D, a mutant protein in which the stoichiometry between
      tetrahydropterin oxidation and amino acid hydroxylation is altered, the (D)k(cat)
      value with [4-(2)H]-phenylalanine is 0.92 but is normal with [3,5-(2)H(2)]
      phenylalanine. The ratio of tetrahydropterin oxidation to amino acid
      hydroxylation for Delta117PheH V379D shows a similar inverse isotope effect with
      [4-(2)H]-phenylalanine. Intramolecular isotope effects, determined from the
      deuterium contents of the tyrosine formed from [4-(2)H]-and [3,5(2)H(2)]
      phenylalanine, are identical for Delta117PheH and Delta117PheH V379D, suggesting
      that steps subsequent to oxygen addition are unaffected in the mutant protein.
      The inverse effects are consistent with the reaction of an activated ferryl-oxo
      species at the para position of the side chain of the amino acid to form a
      cationic intermediate. The normal effects on the (D)k(cat) value for the wild
      type enzyme are attributed to an isotope effect of 5.1 on the tautomerization of
      a dienone intermediate to tyrosine with a rate constant 6- to7-fold that for
      hydroxylation. In addition, there is a slight ( approximately 34%) preference for
      the loss of the hydrogen originally at C4 of phenylalanine. With (2)H(5)-indole
      tryptophan as a substrate for Delta117PheH, the (D)k(cat) value is 0.89,
      consistent with hydroxylation being rate-limiting in this case. When deuterated
      phenylalanines are used as substrates for TrpH, the (D)k(cat) values are within
      error of those for Delta117PheH V379D. Overall, these results are consistent with
      the aromatic amino acid hydroxylases all sharing the same chemical mechanism, but
      with the isotope effect for hydroxylation by PheH being masked by tautomerization
      of an enedione intermediate to tyrosine.

PMID- 16953591
TI  - ATP binding properties of the soluble part of the KdpC subunit from the
      Escherichia coli K(+)-transporting KdpFABC P-type ATPase.
AB  - P-Type ATPases catalyze the transport of cations across the cell envelope via
      site-specific hydrolysis of ATP. Modulation of enzyme activity by additional
      small subunits and/or a second regulatory nucleotide binding site is still a
      subject of discussion. In the K(+)-transporting KdpFABC complex of Escherichia
      coli, KdpB resembles the catalytic P-type ATPase subunit, but ATP binding also
      occurs in the essential but noncatalytic subunit, KdpC. For further
      characterization, the soluble portion of KdpC (KdpC(sol), residues Asn39-Glu190)
      was synthesized separately and purified to homogeneity via affinity and size
      exclusion chromatography. Protein integrity was confirmed by N-terminal
      sequencing, mass spectrometry, and circular dichroism spectroscopy, which
      revealed an alpha-helical content of 44% together with an 8% beta-sheet
      conformation consistent with the values deduced from the primary sequence. The
      overall protein structure was not affected by the addition of ATP to a
      concentration of up to 2 mM. In contrast, labeling of KdpC(sol) with the
      photoreactive ATP analogue 8-azido-ATP resulted in the specific incorporation of
      one molecule of 8-azido-ATP per peptide. No labeling could be observed upon
      denaturation of the protein with 0.2% sodium dodecyl sulfate, which suggests the
      presence of a structured nucleotide binding site. Labeling could be inhibited by
      preincubation with either ATP, ADP, AMP, GTP, or CTP, thus demonstrating a low
      specificity for nucleotides. Following 8-azido-ATP labeling and tryptic digestion
      of KdpC(sol), mass spectrometry showed that ATP binding occurred within the
      Val144-Lys161 peptide located within the C-terminal part of KdpC, thereby further
      demonstrating a defined nucleotide binding site. On the basis of these findings,
      a cooperative model in which the soluble part of KdpC activates catalysis of KdpB
      is suggested.

PMID- 16953592
TI  - Interaction energy contributions of H-bonded and stacked structures of the AT and
      GC DNA base pairs from the combined density functional theory and intermolecular
      perturbation theory approach.
AB  - Stacked and Watson-Crick structures of DNA base pairs are investigated with the
      DFT-SAPT variant of intermolecular perturbation theory, yielding a rigorous
      decomposition of the interaction energy into electrostatic, induction,
      dispersion, and exchange contributions. Their interplay in the various structures
      is analyzed. Total interaction energies extrapolated to the complete basis set
      limit are compared with corresponding second-order Moller-Plesset and estimated
      coupled-cluster theory results.

PMID- 16953593
TI  - Two-dimensional electronic conjugation: cooperative folding and fluorescence
      switching.
AB  - Conformational switching of tris(N-salicylideneamine)-derived C3-symmetric
      molecules could be driven by organizing and disrupting mutually reinforcing
      hydrogen bonding networks. The emission properties associated with these shape
      adaptive constructs respond reversibly to external signal input. Notably,
      significant enhancement in fluorescence efficiency was achieved through
      structural rigidification of the [pi,pi]/[n,pi]-conjugated molecular core.

PMID- 16953594
TI  - A metal-organic framework with entatic metal centers exhibiting high gas
      adsorption affinity.
AB  - A metal-organic framework, PCN-9, containing entatic metal centers, has been
      synthesized and crystallographically characterized. The H2 and CH4 adsorption
      enthalpies of PCN-9 are among the highest reported thus far.

PMID- 16953595
TI  - Imaging farnesyl protein transferase using a topologically activated probe.
AB  - We report on the development and application of a "smart" activatable peptide
      based probe for detection of Ras-related farnesyl protein transferase (FPT). Upon
      farnesylation by FPT, the probe was brought close to a hydrophobic milieu and as
      a consequence emitted fluorescent light that could be detected by several media,
      such as fluorescence microscopy, a plate reader, and an optical imaging system. A
      FPT activity assay confirmed the specificity of the probe (IC50 = 1.2 muM) for
      FPT compared to that of the native peptide (IC50 = 0.17 muM). In addition, the
      probe has remarkable binding constant, Kd = 26 nM. The specificity of enzyme
      activation was proved in pure enzyme assays as well as in cell-based assays.
      Furthermore, the fluorescent enhancement of the probe was 30-fold stronger than
      the control peptide in a live cell assay.

PMID- 16953596
TI  - X-ray scattering study of the effect of hydration on the cross-beta structure of
      amyloid fibrils.
AB  - We have investigated the effect of sample hydration on the wide-angle X-ray
      scattering patterns of amyloid fibrils from two different sources, hen egg white
      lysozyme (HEWL) and an 11-residue peptide taken from the sequence of
      transthyretin (TTR105-115). Both samples show an inter-strand reflection at 4.7 A
      and an inter-sheet reflection which occurs at 8.8 and approximately 10 A for
      TTR105-115 and HEWL fibrils, respectively. The positions, widths, and relative
      intensities of these reflections are conserved in patterns obtained from dried
      stalks and hydrated samples over a range of fibril concentrations. In 2D
      scattering patterns obtained from flow-aligned hydrated samples, the inter-strand
      and inter-sheet reflections showed, respectively, axial and equatorial alignment
      relative to the fibril axis, characteristic of the cross-beta structure. Our
      results show that the cross-beta structure of the fibrils is not a product of the
      dehydrating conditions typically employed to produce aligned samples, but is
      conserved in individual fibrils in hydrated samples under dilute conditions
      comparable to those associated with other biophysical and spectroscopic
      techniques. This suggests a structure consisting of a stack of two or more sheets
      whose interfaces are inaccessible to bulk water.

PMID- 16953597
TI  - Hydrogen storage in chemically reducible mesoporous and microporous Ti oxides.
AB  - Chemically reducible micro- and mesoporous Ti oxides with controlled pore sizes
      from 12 to 26 A were synthesized. The hydrogen storage and adsorption capacity at
      77 K was tested as a function of surface area, pore size, and reducing agent.
      Surprisingly, the oxidation state of the surface Ti species had an even greater
      effect on the storage densities than surface area or pore size. For example, the
      12 A material reduced with bis(toluene) Ti possesses a surface area of less than
      300 m2/g, but absorbs up to 4.94 wt % and 40.46 kg/m3 of H2 reversibly at 77 K
      and 100 atm. This volumetric storage capacity is higher than that of AX-21, which
      has a much higher surface area. The H2 binding enthalpies increased from 4.21
      kJ/mol to 8.08 kJ/mol as the surface oxidation state of the Ti decreased. These
      results suggest that a Kubas-type sigma H2 complex may be involved and that
      further tuning of the H2 binding enthalpies through use of appropriate
      organometallic reagents may achieve even higher storage levels at more moderate
      temperature.

PMID- 16953598
TI  - Simulated unfolded-state ensemble and the experimental NMR structures of villin
      headpiece yield similar wide-angle solution X-ray scattering profiles.
AB  - With the advent of powerful synchrotron sources, solution X-ray scattering is
      being increasingly used to get basic information about the structure of
      polypeptides. The solution scattering technique essentially provides one
      dimensional data, which are then interpreted in terms of a three-dimensional
      structure through model building. Here we calculate wide-angle solution
      scattering patterns for an ensemble of simulated unfolded structures of villin
      headpiece, which differ from the native structure by rmsd = 8.8 +/- 1.0 A and
      have only negligible amounts of native secondary structure. We show that the wide
      angle solution scattering pattern of such an ensemble shares significant
      similarity with the one based on the experimental NMR structures of the molecule.
      Our results suggest that solution scattering in the wide-angle limit, by itself,
      provides very little information about the secondary structure content of a
      polypeptide or its side-chain packing.

PMID- 16953599
TI  - Unique organic-inorganic interactions leading to a structure-directed microporous
      aluminophosphate crystallization as observed with in situ Raman spectroscopy.
AB  - We report on the direct observation of key organic template-framework
      interactions leading to the formation of specific aluminophosphate structures. In
      particular, we show how MeAPO-34 formation was governed by an interaction between
      the divalent framework substituted metal ion and the template conformation, while
      for AlPO-5 the structure formation was determined by the template conformation
      alone. Understanding such interactions therefore appears to be important for the
      rationalization of microporous material formation.

PMID- 16953600
TI  - A metallic (EDT-DSDTFVSDS)2.FeBr4 salt: antiferromagnetic ordering of d spins of
      FeBr4- ions and anomalous magnetoresistance due to preferential pi-d interaction.
AB  - The 2:1 salt of a new donor molecule, EDT-DSDTFVSDS with FeBr4- ion, (EDT
      DSDTFVSDS)2.FeBr4 showed an essentially metallic behavior despite a small upturn
      in the electrical resistance below ca. 30 K (electrical conductivities at 290 and
      4.2 K are 200 and 170 S cm-1, respectively). The Fe(III) d spins of the FeBr4-
      ions in this salt were subject to antiferromagnetic ordering at 3.3 K by virtue
      of a strong pi-d interaction (Jpid) which is comparable to that in a molecular
      metallic conductor, lambda-(BETS)2.FeCl4, and of a very weak d-d interaction
      (Jdd). This strong pi-d interaction was evidenced by a large and negative
      magnetoresistance effect (ca. 20% at 5 T) as well as by the appearance of a large
      dip in the resistance at the magnetic field (ca. 2.0 T) parallel to the easy axis
      for the spin-flop transition of the Fe(III) d spins.

PMID- 16953601
TI  - Direct C-H arylation of (hetero)arenes with aryl iodides via rhodium catalysis.
AB  - A new method for the catalytic C-H arylation of heteroarenes and arenes that
      manifests high activity paired with reasonably broad scope was developed. Under
      the catalytic influence of RhCl(CO){P[OCH(CF3)2]3}2 and Ag2CO3, the direct C-H
      arylation of heteroarenes/arenes with aryl/heteroaryl iodides took place to
      afford a range of biaryls in good to excellent yields with high regioselectivity.
      Thiophenes, furans, pyrroles, indoles, and alkoxybenzenes are applicable in this
      arylation protocol.

PMID- 16953602
TI  - Externally tunable dynamic confinement effect in organosilica sol-gels.
AB  - The feasibility of using the pores of organosilica sol-gels for dynamic
      confinement of a luminescent molecule is demonstrated in this paper. The porous
      organosilica sol-gels act as reversible thermoresponsive materials which exhibit
      reduced pore volume at higher temperature and enlarged pores at lower
      temperature, which causes dynamic alterations in the nanoenvironment of
      encapsulated entities. A particularly remarkable feature of this system is that
      the temperature-dependent confinement effect provided by the gels is reversible
      and can be efficiently modulated by simply changing the temperature.

PMID- 16953603
TI  - A convergent and enantioselective synthesis of (+)-amurensinine via selective C-H
      and C-C bond insertion reactions.
AB  - A convergent and enantioselective synthesis of the natural product amurensinine
      is described. The synthetic strategy takes advantage of mild and selective C-H
      and C-C bond insertion reactions, in addition to the palladium-catalyzed aerobic
      oxidative kinetic resolution recently developed in these laboratories.

PMID- 16953604
TI  - Rhodium-catalyzed stereoselective formation of Z-enamines from allylaziridines.
AB  - Rhodium (I)-catalyzed isomerization of N-allylaziridines affords isolable Z
      enamines in excellent yields and with high stereoselectivity. Cationic
      [Rh(BINAP)(COD)]OTf and RhH(CO)(PPh3)3 follow the same selectivity toward the Z
      isomers. This selectivity is not observed with other N-allylamines which give the
      thermodynamically more stable E-isomers. These unexpected results suggest a
      possible deviation from the commonly accepted mechanism of isomerization.
      Preliminary results show that the Z-enamines undergo cycloaddition with DMAD to
      form highly strained N-cyclobutenyl aziridines.

PMID- 16953605
TI  - Removal of a single minor-groove functional group eliminates A-tract curvature.
AB  - Much of the work in studying the phenomenon of A-tract curvature has involved the
      insertion of modified residues into the A-tract sequence and then cross
      correlation of the structural differences with the resulting curvature effects.
      In the A-tract sequence d(A-T)5, removal of a single functional group (the O2
      carbonyl of the central dT residue) by its replacement with hydrogen completely
      eliminates the curvature properties. This atom-specific change was accomplished
      by using the C-nucleoside dm32P in which the O2-carbonyl is replaced with -H but
      normal Watson-Crick hydrogen bonding is maintained. Similar derivatives with -F
      (dF62P) or -CH3 (dm62P) when present for the central dT residue also eliminate
      curvature. Finally, we have shown that the extent of curvature for sequences
      containing this carbonyl are sensitive to the [Mg2+], while those lacking the
      carbonyl show little to no Mg2+ dependence, strongly suggesting, we believe, a
      role for Na+/Mg2+ cooperative interactions in the minor groove to explain the
      curvature phenomenon.

PMID- 16953606
TI  - Monodisperse lanthanide oxysulfide nanocrystals.
AB  - Monodisperse lanthanide oxysulfide nanoplates and short nanorods were synthesized
      by the thermal decomposition of molecular precursors in the presence of oxygen.
      The nanoplates have uniform thicknesses and further self-organize to nanowires up
      to micron scale. The Eu2O2S and Eu3+-doped Gd2O2S nanocrystals both show unusual
      fluorescence properties obviously differing from the bulk powder phosphors, which
      are related to the surface-modification effects.

PMID- 16953607
TI  - Phosphorus-containing hybrid calixphyrins: promising mixed-donor ligands for
      visible and efficient palladium catalysts.
AB  - Phosphorus-sulfur-containing hybrid calixphyrins were prepared by the BF3
      promoted dehydrative condensation between sigma4-2,5-bis[(pyrrol-2
      yl)methyl]phosphole and 2,5-bis[hydroxy(phenyl)methyl]thiophene. X-ray
      crystallographic analysis of the Pd-P,N2,S-hybrid calixphyrin complex revealed
      that the Pd center was coordinated by the four heteroatoms to adopt a distorted
      square planar geometry. The Pd complex, displaying a characteristic reddish
      purple color in solution, catalyzed the Heck reaction of bromoarenes with n-butyl
      acrylate with high efficiency at elevated temperatures.

PMID- 16953608
TI  - Self-coiling of Ag2V4O11 nanobelts into perfect nanorings and microloops.
AB  - Free-standing Ag2V4O11 nanorings and microloops have been synthesized by a simple
      hydrothermal process without any template or surfactant. The Ag2V4O11 nanorings
      and microloops have preferred growth direction along the [30] plane and are
      formed by the self-rolling of Ag2V4O11 nanobelts.

PMID- 16953609
TI  - Progressive-convergent elucidation of stereochemistry in complex polyols. The
      absolute configuration of (-)-sagittamide A.
AB  - The absolute stereostructure of sagittamide A (1), a O-hexacetyl long-chain
      hexahydroxy-alpha,omega-dicarboxylic acid, was assigned using a progressive
      convergent approach that integrates three powerful regimens for stereochemical
      analysis of acyclic natural products: J-based analysis, 13C NMR universal
      database comparisons, and exciton coupling circular dichroism.

PMID- 16953610
TI  - Enantioselective intramolecular [2 + 2 + 2] cycloaddition of 1,4-diene-ynes: a
      new approach to the construction of quaternary carbon stereocenters.
AB  - The intramolecular [2 + 2 + 2] cycloaddition of various 1,4-diene-ynes was
      examined using a chiral rhodium catalyst. In the case of 1,4-diene-ynes with a
      substituent at the 2-position of the 1,4-diene moiety, tricyclic compounds
      possessing a strained bicyclo[2.2.1]heptene skeleton with two quaternary carbon
      stereocenters were obtained in high enantiomeric excess. On the other hand, in
      the case of 1,4-diene-ynes with no substituent at this position, bicyclic
      cyclohexa-1,3-dienes with a quaternary carbon stereocenter were obtained probably
      by carbon-carbon bond cleavage of the reaction intermediate.

PMID- 16953611
TI  - Rate acceleration in olefin metathesis through a fluorine-ruthenium interaction.
AB  - The synthesis, structure, and performance of new ruthenium-based olefin
      metathesis catalysts, featuring fluorinated NHC ligands are presented. The
      introduction of halogen atoms into the N-heterocyclic carbene ligand profoundly
      alters the catalytic activity and can afford a more efficient catalyst.
      Structural investigations suggest that a fluorine-ruthenium interaction is
      responsible for this increased activity.

PMID- 16953612
TI  - Sequential catalytic isomerization and allylic substitution. Conversion of
      racemic branched allylic carbonates to enantioenriched allylic substitution
      products.
AB  - A catalytic protocol for the conversion of readily accessible racemic, branched
      aromatic allylic esters to branched allylic amines, ethers, and alkyls has been
      developed. Palladium-catalyzed isomerization of branched allylic esters to
      terminal allylic esters, followed by sequential iridium-catalyzed allylic
      substitution, gave the branched allylic products in good yield with high
      regioisomeric and enantiomeric selectivity. Both electron-rich and electron-poor
      branched allylic esters gave products in >90% ee. High enantiomeric excesses were
      also observed for the products from the reactions of 2-thienyl acetates and
      dienyl carbonates.

PMID- 16953613
TI  - Versatile, fragrant, convertible isonitriles.
AB  - The metalation of oxazoles leads to ring opening to the isocyanoenolate that can
      be O-acylated to give the unsaturated isonitriles. These substances undergo
      conventional multicomponent reactions. The products of their reactions are
      readily converted to acyl substitution products by treatment with acid and a
      nucleophile. These unsaturated isonitriles are notable by their simple
      preparations and, unusually, their nonoffensive odors.

PMID- 16953614
TI  - Highly efficient Rh(I)-catalyzed asymmetric hydrogenation of enamines using
      monodente spiro phosphonite ligands.
AB  - A highly enantioselective hydrogenation of nonfunctionalized enamines has been
      developed by using rhodium complexes of chiral spiro phosphonite ligands,
      providing chiral tertiary amines in excellent enantioselectivities.

PMID- 16953615
TI  - Mixed La-Li heterobimetallic complexes for tertiary nitroaldol resolution.
AB  - A kinetic resolution of tertiary nitroaldols derived from simple ketones is
      described. Mixed BINOL/biphenol La-Li heterobimetallic complexes gave the best
      selectivity in retro-nitroaldol reactions of racemic tertiary nitroaldols. By
      using a mixture of La-Li3-(1a)3 complex (LLB 2a) and La-Li3-(1b)3 (LLB* 2b)
      complex in a ratio of 2/1, chiral tertiary nitroaldols were obtained in 80-97% ee
      and 30-47% recovery yield.

PMID- 16953616
TI  - Design of a bacterial host for site-specific incorporation of p
      bromophenylalanine into recombinant proteins.
AB  - Introduction of a yeast suppressor tRNA (ytRNA(Phe)(CUA)) and a mutant yeast
      phenylalanyl-tRNA synthetase (yPheRS (T415G)) into an Escherichia coli expression
      host allows in vivo incorporation of phenylalanine analogues into recombinant
      proteins in response to amber stop codons. However, high-fidelity incorporation
      of non-natural amino acids is precluded in this system by mischarging of
      ytRNA(Phe)(CUA) with tryptophan (Trp) and lysine (Lys). Here we show that
      ytRNA(Phe)(CUA) and yPheRS can be redesigned to achieve high-fidelity amber codon
      suppression through delivery of p-bromophenylalanine (pBrF). Two strategies were
      used to reduce misincorporation of Trp and Lys. First, Lys misincorporation was
      eliminated by disruption of a Watson-Crick base pair between nucleotides 30 and
      40 in ytRNA(Phe)(CUA). Loss of this base pair reduces mischarging by the E. coli
      lysyl-tRNA synthetase. Second, the binding site of yPheRS was redesigned to
      enhance specificity for pBrF. Specifically, we used the T415A variant, which
      exhibits 5-fold higher activity toward pBrF as compared to Trp in ATP-PP(i)
      exchange assays. Combining mutant ytRNA(Phe)(CUA) and yPheRS (T415A) allowed
      incorporation of pBrF into murine dihydrofolate reductase in response to an amber
      codon with at least 98% fidelity.

PMID- 16953617
TI  - Facile amine formation by intermolecular catalytic amidation of carbon-hydrogen
      bonds.
AB  - A simple copper-based catalytic system has been developed for the carbon-hydrogen
      amidation reaction. The copper-homoscorpionate complex Tp(Br3)Cu(NCMe) catalyzes
      the transfer of the nitrene unit NTs (Ts = p-toluenesulfonyl) and its subsequent
      insertion into the sp(3) C-H bonds of alkyl aromatic and cyclic ethers or the
      sp(2) C-H bonds of benzene using PhI=NTs as the nitrene source, affording the
      corresponding trisubstitued NR(1)HTs amines in moderate to high yields. The use
      of the environmentally friendly chloramine-T has also proven effective, with the
      advantage that sodium chloride is formed as the only byproduct. A tandem, one-pot
      consecutive nitrene-carbene insertion system has been developed to yield amino
      acid derivatives.

PMID- 16953618
TI  - Ion/molecule reactions of cation radicals formed from protonated polypeptides via
      gas-phase ion/ion electron transfer.
AB  - Cation radicals formed via gas-phase electron transfer to multiply protonated
      polypeptides have been found to react with molecular oxygen. Such cation radicals
      are of interest within the context of electron transfer dissociation, a
      phenomenon with high utility for the characterization of peptide and protein
      primary structures. Most of the cation radicals show the attachment of O(2) under
      room temperature storage conditions in an electrodynamic ion trap. At higher
      temperatures and under conditions of collisional activation, the oxygen adduct
      species lose O(2), HO(*), or HO(2)(*), depending upon the identity of the side
      chain at the radical site. The fragments containing the C-terminus, the so-called
      z-ions, which are predominantly radical species, engage in reactions with
      molecular oxygen. This allows for the facile distinction between z-ions and their
      complementary even-electron c-ion counterparts. Such a capability has utility in
      protein identification and characterization via mass spectrometry. Intact
      electron transfer products also show oxygen attachment. Subsequent activation of
      such adducts show dissociation behavior very similar to that noted for z-ion
      adducts. These observations indicate that ion/radical reactions can be used to
      probe the locations of radical sites in the undissociated electron transfer
      products as well as distinguish between c- and z-type ions.

PMID- 16953620
TI  - Metallosupramolecular chemistry with bis(benzene-o-dithiolato) ligands.
AB  - The bis(benzene-o-dithiol) ligands H(4)-1, H(4)-2, and H(4)-3 react with
      [Ti(OC(2)H(5))(4)] to give dinuclear triple-stranded helicates [Ti(2)L(3)](4)(-)
      (L = 1(4)(-), 2(4)(-), 3(4)(-)). NMR spectroscopic investigations revealed that
      the complex anions possess C(3) symmetry in solution. A crystal structure
      analysis for (PNP)(4)[Ti(2)(2)(3)] ((PNP)(4)[14]) confirmed the C(3) symmetry for
      the complex anion in the solid state. The complex anion in
      Li(PNP)(3)[Ti(2)(1)(3)] (Li(PNP)(3)[13]) does not exhibit C(3) symmetry in the
      solid state due to the formation of polymeric chains of lithium bridged complex
      anions. Complexes [13](4)(-) and [14](4)(-) were obtained as racemic mixtures of
      the Delta,Delta and Lambda,Lambda isomers. In contrast to that, complex
      (PNP)(4)[Ti(2)(3)(3)] ((PNP)(4)[15]) with the enantiomerically pure chiral ligand
      3(4)(-) shows a strong Cotton effect in the CD spectrum, indicating that the
      chirality of the ligands leads to the formation of chiral metal centers. The o
      phenylene diamine bridged bis(benzene-o-dithiol) ligand H(4)-4 reacts with Ti(4+)
      to give the dinuclear double-stranded complex Li(2)[Ti(2)(4)(2)(mu-OCH(3))(2)]
      containing two bridging methoxy ligands between the metal centers. The crystal
      structure analysis and the (1)H NMR spectrum of (Ph(4)As)(2)[Ti(2)(4)(2)(mu
      OCH(3))(2)] ((Ph(4)As)(2)[(16]) reveal C(2) symmetry for the anion
      [Ti(2)(4)(2)(mu-OCH(3))(2)](2)(-). For a comparative study the dicatechol ligand
      H(4)-5, containing the same o-phenylene diamine bridging group as the bis(benzene
      o-dithiol) ligands H(4)-4, was prepared and reacted with [TiO(acac)(2)] to give
      the dinuclear complex anion [Ti(2)(5)(2)(mu-OCH(3))(2)](2)(-). The molecular
      structure of (PNP)(2)[Ti(2)(5)(2)(mu-OCH(3))(2)] ((PNP)(2)[17]) contains a
      complex anion which is similar to [16](2)(-), with the exception that strong N
      H...O hydrogen bonds are formed in complex anion [17](2)(-), while N-H...S
      hydrogen bonds are absent in complex anion [16](2)(-).

PMID- 16953619
TI  - Total synthesis of piericidin A1 and B1 and key analogues.
AB  - Full details of the total synthesis of piericidin A1 and B1 and its extension to
      the preparation of a series of key analogues are described including ent
      piericidin A1 (ent-1), 4'-deshydroxypiericidin A1 (58), 5'-desmethylpiericidin A1
      (73), 4'-deshydroxy-5'-desmethylpiericidin A1 (75), and the corresponding
      analogues 51, 59, 76, and 77 bearing a simplified farnesyl side chain. The
      evaluation of these key analogues, along with those derived from their further
      functionalizations, permitted a scan of the key structural features providing new
      insights into the role of the substituents found in both the pyridyl core as well
      as the side chain. A strategic late stage heterobenzylic Stille cross-coupling
      reaction of the pyridyl core with the fully elaborated side chain permitted ready
      access to the analogues in which each half of the molecule could be
      systematically and divergently modified. The pyridyl cores were assembled
      enlisting inverse electron demand Diels-Alder reactions of N-sulfonyl-1
      azabutadienes, while key elements of side chain syntheses include an anti
      selective asymmetric aldol to install the C9 and C10 relative and absolute
      stereochemistry (for natural and ent-1) and a modified Julia olefination for
      formation of the C5-C6 trans double bond with convergent assemblage of the side
      chains.

PMID- 16953621
TI  - Hydrogen-bond symmetry in zwitterionic phthalate anions: symmetry breaking by
      solvation.
AB  - The cationic nitrogen of zwitterion 1 is located symmetrically with respect to
      its intramolecular OHO hydrogen bond. Incorporation of one (18)O allows
      investigation of the H-bond symmetry by the NMR method of isotopic perturbation.
      In both CD(3)OD and CD(2)Cl(2) equilibrium isotope shifts are detected at the
      carboxyl and ipso carbons. Therefore, 1 exists as a pair of interconverting
      tautomers, not as a single symmetric structure with its hydrogen centered between
      the two oxygens. The H-bond is instantaneously asymmetric, and there is an
      equilibrium between solvatomers (isomers or stereoisomers that differ in
      solvation). The broader implications of this result regarding the role of the
      local environment ("solvation") in breaking symmetry are discussed.

PMID- 16953623
TI  - Binding free energy contributions of interfacial waters in HIV-1
      protease/inhibitor complexes.
AB  - Water molecules are commonly observed in crystal structures of protein-ligand
      complexes where they mediate protein-ligand binding. It is of considerable
      theoretical and practical importance to determine quantitatively the individual
      free energy contributions of these interfacial water molecules to protein-ligand
      binding and to elucidate factors that influence them. The double-decoupling free
      energy molecular dynamics simulation method has been used to calculate the
      binding free energy contribution for each of the four interfacial water molecules
      observed in the crystal structure of HIV-1 protease complexed with KNI-272, a
      potent inhibitor. While two of these water molecules contribute significantly to
      the binding free energy, the other two have close to zero contribution. It was
      further observed that the protonation states of two catalytic aspartate residues,
      Asp25 and Asp125, strongly influence the free energy contribution of a conserved
      water molecule Wat301 and that different inhibitors significantly influence the
      free energy contribution of Wat301. Our results have important implications on
      our understanding of the role of interfacial water molecules in protein-ligand
      binding and to structure-based drug design aimed at incorporating these
      interfacial water molecules into ligands.

PMID- 16953624
TI  - Investigation of two-photon absorption properties in branched alkene and alkyne
      chromophores.
AB  - Novel alkene and alkyne branched structures have been synthesized, and their two
      photon absorption (2PA) properties are reported. This series of alkene and alkyne
      trimer systems tests the mechanistic approach for enhancing the 2PA process which
      is usually dictated by the pi-bridging, delocalization length, and corresponding
      charge transfer on the 2PA cross sections. The results suggest that alkene
      branched systems have higher 2PA cross sections. While steady-state absorption
      and emission measurements were not successful in predicting the observed trend of
      2PA cross sections, time-resolved measurements have explained the trends
      observed. It was found that, upon photoexcitation, there is an ultrafast charge
      localization to an intramolecular charge-transfer (ICT) state, followed by the
      presence of a solvent and conformationally relaxed ICT state in these branched
      systems.

PMID- 16953622
TI  - Separation of tricomponent protein mixtures with triblock nanorods.
AB  - Two-component triblock magnetic nanorods with gold end blocks and nickel interior
      blocks have been synthesized and used as affinity templates for the simultaneous
      and efficient separation of a three-component protein mixture. The gold blocks
      were selectively functionalized with 11-amino-1-undecanethiol, and then
      glutaraldehyde was used to covalently attach nitrostreptavidin to them. His
      tagged proteins bind to the nickel block and biotin-tagged proteins bind to the
      functionalized gold ends, allowing one to separate a mixture of three proteins
      with a single material. Each surface-bound protein can be released selectively
      using imidazole for the His-tagged protein and biotin for the biotinylated
      protein.

PMID- 16953625
TI  - Resonance bonding patterns of peroxide chemistry: cyclic three-center
      hyperbonding in "phosphadioxirane" intermediates.
AB  - We investigate the nature of valency and bonding in the highly unusual O(2)PR(3)
      "phosphadioxirane" species recently isolated as an intermediate in the reaction
      of (1)O(2) with organic phosphines PR(3). Commonly, this species is depicted as a
      Lewis structure with five bonds at the phosphorus center, suggesting hypervalent
      involvement of extra-valence d-orbitals in the hybridization. However,
      nonhypervalent bonding patterns, such as open zwitterionic peroxides or
      R(2)PO(2)(+)R(-) ion pairs, could also achieve the observed hypercoordination. In
      the present work, we employ ab initio and hybrid density functional calculations
      with theoretical analysis by means of Natural Resonance Theory (NRT) and Natural
      Bond Orbitals (NBOs) to investigate the role of valence shell expansion versus
      nonhypervalent ionic resonance in phosphadioxiranes. We find that true
      hypervalency is relatively negligible in phosphadioxiranes, and hypercoordination
      is instead achieved through both conventional linear Pimentel-Rundle three
      center, four-electron (3c/4e) hyperbonding as well as an unprecedented cyclic
      form of 3c/4e hyperbonding. We examine ramifications and limits of the cyclic
      hyperbonding phenomenon in analogous carbon compounds and discuss some broader
      implications of its structural representation and nomenclature.

PMID- 16953626
TI  - Optimization, standardization, and testing of a new NMR method for the
      determination of zeolite host-organic guest crystal structures.
AB  - An optimized and automated protocol for determining the location of guest sorbate
      molecules in highly siliceous zeolites from (29)Si INADEQUATE and (1)H/(29)Si
      cross polarization (CP) magic-angle spinning (MAS) NMR experiments is described.
      With the peaks in the (29)Si MAS NMR spectrum assigned to the unique Si sites in
      the zeolite framework by a 2D (29)Si INADEQUATE experiment, the location of the
      sorbate molecule is found by systematically searching for sorbate locations for
      which the measured rates of (1)H/(29)Si cross polarization of the different Si
      sites correlate linearly with (1)H/(29)Si second moments calculated from H-Si
      distances. Due to the (1)H/(29)Si cross polarization being in the "slow CP
      regime" for many zeolite-sorbate complexes, it is proposed that the CP rate
      constants are best measured by (1)H/(29)Si cross polarization drain experiments,
      if possible, to avoid complications that may arise from fast (1)H and (29)Si
      T(1)rho relaxations. An algorithm for determining the sorbate molecule location
      is described in detail. A number of ways to effectively summarize and display the
      large number of solutions which typically result from a prediction of the
      structure from the CP MAS NMR data are presented, including estimates of the
      errors involved in the structure determinations. As a working example throughout
      this paper, the structure of the low loaded p-dichlorobenzene/ZSM-5 complex is
      determined under different conditions from solid-state (1)H/(29)Si CP MAS NMR
      data, and the solutions are shown to be in excellent agreement with the known
      single-crystal X-ray diffraction structure. This structure determination approach
      is shown to be quite insensitive to the use of relative rate constants rather
      than absolute values, to the detailed structure of the zeolite framework, and
      relatively insensitive to temperature and motions.

PMID- 16953627
TI  - Cruciforms as functional fluorophores: response to protons and selected metal
      ions.
AB  - The photophysics of dialkylamino- and/or pyridine-containing functional
      chromophores, 1,4-distyryl-2,5-bis(ethynylaryl)benzenes (cruciforms) was
      investigated; their fluorescence quantum yields and emissive lifetimes were
      determined. Depending upon their substituents, the frontier molecular orbitals
      (FMOs) of these cruciforms are either congruent, i.e., HOMO and LUMO occupy the
      same real space, or disjoint, i.e., the HOMO is located on one branch of the
      cruciform while the LUMO is located on the second one. Donor-acceptor
      substitution leads to a disjoint FMO pattern, while the parent 1,4-distyryl-2,5
      bis(phenylethynyl)benzene shows congruent FMOs. The photophysics of the
      cruciforms was investigated upon addition of either an excess of trifluoroacetic
      acid or an excess of selected metal (Mg(2+), Ca(2+), Mn(2+), Zn(2+))
      trifluoromethanesulfonate salts. Addition of either metal ions or protons led to
      analogous but not identical changes in the spectroscopic properties of the
      investigated cruciforms. The collected data suggest that the metals bind
      preferentially at the aniline nitrogen and not at the electron-rich arene. The
      spatially separated FMOs permit the independent manipulation of the HOMO and the
      LUMO of such cruciforms. If the branches contain metal-complexing moieties, metal
      binding leads to either a hypsochromic or a bathochromic shift in emission via
      interaction of the metal cations with either the HOMO or the LUMO.

PMID- 16953628
TI  - Phage display affords peptides that modulate beta-amyloid aggregation.
AB  - As the population ages, the need to develop methods to understand and intercept
      the processes responsible for protein aggregation diseases is becoming more
      urgent. The aggregation of the protein beta-amyloid (Abeta) has been implicated
      in Alzheimer's Disease (AD); however, whether the toxic species is a large,
      insoluble aggregate or some lower order form is not yet known. Agents that can
      modulate the aggregation state of Abeta could resolve this controversy by
      facilitating our understanding of the consequences of aggregation and its
      underlying mechanism. To date, however, ligands that bind to specific forms of
      Abeta have not been identified. To address this deficiency, we tested whether
      phage display could yield such ligands by screening libraries against Abeta in
      two different states: monomeric or highly aggregated. Intriguingly, the peptides
      selected had different effects on Abeta aggregation. Peptides selected for
      binding to monomeric Abeta did not perturb aggregation, but those selected using
      highly aggregated Abeta increase the rate of aggregation drastically. The latter
      also alter the morphology of the resulting aggregate. The ability of a peptide to
      promote aggregation correlated with its affinity for the N-terminal 10 residues
      of Abeta. This result indicates that the mechanism by which the peptides
      influence aggregation is related to their affinity for the Abeta N-terminus.
      Thus, the identification of compounds that bind to this Abeta section can afford
      agents that affect aggregation. Moreover, the data suggest that endogenous
      ligands that interact with the N-terminal region can influence the propensity of
      Abeta to form aggregates and the morphology of those that form. Our data
      highlight the utility of phage display for identifying ligands that bind to
      target proteins in different states, and they indicate that such agents can be
      used to perturb protein aggregation.

PMID- 16953629
TI  - FRET templated by G-quadruplex DNA: a specific ternary interaction using an
      original pair of donor/acceptor partners.
AB  - G-quadruplex represents a suitable scaffold for FRET (fluorescence resonance
      energy transfer) since its two external quartets offer two well-defined binding
      sites for concomitant trapping of donor/acceptor partners. Combining selective G
      quadruplex binders (macrocyclic bis(quinacridine) BOQ(1) or monomeric
      quinacridine MMQ(1), donor) with a highly fluorescent DNA probe (thiazole orange,
      acceptor), we designed a structure-specific FRET-system based on an unprecedented
      noncovalent ternary complex. This system could be potentially usable as a
      signature for quadruplex-DNA conformation in solution, but also might offer a
      unique means for observing cation and ligand binding influence on quadruplex
      topology.

PMID- 16953630
TI  - Femtosecond time- and wavelength-resolved fluorescence and absorption
      spectroscopic study of the excited states of adenosine and an adenine oligomer.
AB  - By employing broadband femtosecond Kerr-gated time-resolved fluorescence (KTRF)
      and transient absorption (TA) techniques, we report the first (to our knowledge)
      femtosecond combined time- and wavelength-resolved study on an ultraviolet
      excited nucleoside and a single-stranded oligonucleotide (namely adenosine (Ado)
      and single-stranded adenine oligomer (dA)(20)) in aqueous solution. With the
      advantages of the ultrafast time resolution, the broad spectral and temporal
      probe window, and a high sensitivity, our KTRF and TA results enable the real
      time monitoring and spectral characterization of the excited-state relaxation
      processes of the Ado nucleoside and (dA)(20) oligonucleotide investigated. The
      temporal evolution of the 267 nm excited Ado KTRF spectra indicates there are two
      emitting components with lifetimes of approximately 0.13 ps and approximately
      0.45 ps associated with the L(a) and L(b) pipi* excited states, respectively.
      These Ado results reveal no obvious evidence for the involvement of the npi*
      state along the irradiative internal conversion pathway. A distinct mechanism
      involving only the two pipi* states has been proposed for the ultrafast Ado
      deactivation dynamics in aqueous solution. The time dependence of the 267 nm
      excited (dA)(20) KTRF and TA spectra reveals temporal evolution from an ultrafast
      "A-like" state (with a approximately 0.39 ps decay time) to a relatively long
      lived E(1) "excimer" (approximately 4.3 ps decay time) and an E(2) "excimer-like"
      (approximately 182 ps decay time) state. The "A-like" state has a spectral
      character closely resembling the excited state of Ado. Comparison of the spectral
      evolution between the results for Ado and (dA)(20) provides unequivocal evidence
      for the local excitation character of the initially photoexcited (dA)(20). The
      rapid transformation of the locally excited (dA)(20) component into the
      delocalized E(1) "excimer" state which then further evolves into the E(2)
      "excimer-like" state indicates that base stacking has a high ability to modify
      the excited-state deactivation pathway. This modification appears to occur by
      suppressing the internal conversion pathway of an individually excited base
      component where the stacking interaction mediates efficient interbase energy
      transfer and promotes formation of the collective excited states. This feature of
      the local excitation that is subsequently followed by rapid energy delocalization
      into nearby bases may occur in many base multimer systems. Our results provide an
      important new contribution to better understanding DNA photophysics.

PMID- 16953631
TI  - Synthetic studies of complex immunostimulants from Quillaja saponaria: synthesis
      of the potent clinical immunoadjuvant QS-21Aapi.
AB  - QS-21 is one of the most promising new adjuvants for immune response potentiation
      and dose-sparing in vaccine therapy given its exceedingly high level of potency
      and its favorable toxicity profile. Melanoma, breast cancer, small cell lung
      cancer, prostate cancer, HIV-1, and malaria are among the numerous maladies
      targeted in more than 80 recent and ongoing vaccine therapy clinical trials
      involving QS-21 as a critical adjuvant component for immune response
      augmentation. QS-21 is a natural product immunostimulatory adjuvant, eliciting
      both T-cell- and antibody-mediated immune responses with microgram doses. Herein
      is reported the synthesis of QS-21A(api) in a highly modular strategy, applying
      novel glycosylation methodologies to a convergent construction of the potent
      saponin immunostimulant. The chemical synthesis of QS-21 offers unique
      opportunities to probe its mode of biological action through the preparation of
      otherwise unattainable nonnatural saponin analogues.

PMID- 16953632
TI  - Isolation, structure, and absolute stereochemistry of platensimycin, a broad
      spectrum antibiotic discovered using an antisense differential sensitivity
      strategy.
AB  - Fatty acids are essential for survival of bacteria and are synthesized by a
      series of enzymes including the elongation enzymes, beta-ketoacyl acyl carrier
      protein synthase I/II (FabF/B). Inhibition of fatty acid synthesis is one of the
      new targets for the discovery and development of antibacterial agents.
      Platensimycin (1a) is a novel broad spectrum Gram-positive antibiotic produced by
      Streptomyces platensis. It was discovered by target-based whole-cell screening
      strategy using antisense differential sensitivity assay. It inhibits bacterial
      growth by selectively inhibiting condensing enzyme FabF of the fatty acid
      synthesis pathway and was isolated by a two-step process, a capture step followed
      by reversed-phase HPLC. The structure was elucidated by 2D NMR methods and
      confirmed by X-ray crystallographic analysis of a bromo derivative. It was
      determined that potential reactivity of the enone moiety does not play a key role
      in the biological activity of platensimycin. However, cyclohexenone ring
      conformation renders for the stronger binding interaction with the enzyme. The
      isolation, structure elucidation, derivatization, and biological activity of 6,7
      dihydroplatensimycin are described.

PMID- 16953633
TI  - Rational synthesis, self-assembly, and optical properties of PbS-Au heterogeneous
      nanostructures via preferential deposition.
AB  - High-quality, monodisperse PbS-Au(1), PbS-Au(4), and PbS-Au(n) nanostructures
      have been synthesized via a facile and convenient solution chemistry approach.
      HRTEM images of these nanostructures showed good selectivity of gold deposition
      on the semiconductor in several spatially correlated directions. The formation of
      these regular nanostructures can be explained by the difference in polarity of
      crystal facets that led to the selective growth of metal on the semiconductor
      surface. Owing to their narrow size distribution and intrinsic high-symmetry, the
      resulting PbS-Au(4) and PbS-Au(n) heterogeneous nanostructures could
      spontaneously self-assemble into ordered arrays with different symmetries. From
      the results of the pump-probe measurements, the presence of Au in PbS-Au(4)
      nanostructures has substantially altered the nonlinear optical response of PbS
      nanocrystals.

PMID- 16953634
TI  - Silapropargyl/silaallenyl and silylene acetylide complexes of [Cp(CO)2W]+.
      Theoretical study of their interesting bonding nature and formation reaction.
AB  - The geometry and bonding nature of Cp(CO)(2)W(CCH)(SiH(2)) (1) and the reaction
      leading to the formation of 1 from Cp(CO)(2)W(SiH(2)C triple bond CH)(9) were
      theoretically investigated with DFT, MP2 to MP4(SDTQ), and CCSD(T) methods, where
      9 and 1 were adopted as models of the interesting new complexes reported
      recently, Cp*(CO)(2)W(Si(Ph)(2)C triple bond C(t)Bu) and Cp*(CO)(2)W(C triple
      bond C(t)Bu)(SiPh(2)), respectively. Our computational results clearly indicate
      that 1 involves neither a pure silacyclopropenyl group nor pure silylene and
      acetylide groups and that the silylene group strongly interacts with both the W
      center and the acetylide group. Frontier orbitals of 1 resemble those observed in
      the formation of silacyclopropene from silylene and acetylene. The frontier
      orbitals, as well as the geometry, indicate that the (CCH)(SiH(2)) moiety of 1
      can be understood in terms of an interesting intermediate species trapped by the
      W center in that formation reaction. Complex 1 is easily formed from 9 through Si
      C sigma-bond activation with moderate activation barriers of 15.3, 18.8, and 15.8
      kcal/mol, which are the DFT-, MP4(SDTQ)-, and CCSD(T)-calculated values,
      respectively. This reaction takes place without a change of the oxidation state
      of the W center. Intermediate 9 is easily formed from Cp(CO)(2)W(Me)(H(3)SiC
      triple bond CH) via Si-H oxidative addition, followed by C-H reductive
      elimination. The bonding nature of 9 is also very interesting; the nonbonding pi
      orbital of the H(2)SiCCH moiety is essentially the same as that of the propargyl
      group, but the pi-conjugation between Si and C atoms is very weak in the pi
      orbital, unlike that in the propargyl group.

PMID- 16953635
TI  - Substituents on quinone methides strongly modulate formation and stability of
      their nucleophilic adducts.
AB  - Electronic perturbation of quinone methides (QM) greatly influences their
      stability and in turn alters the kinetics and product profile of QM reaction with
      deoxynucleosides. Consistent with the electron-deficient nature of this reactive
      intermediate, electron-donating substituents are stabilizing and electron
      withdrawing substituents are destabilizing. For example, a dC N3-QM adduct is
      made stable over the course of observation (7 days) by the presence of an
      electron-withdrawing ester group that inhibits QM regeneration. Conversely, a
      related adduct with an electron-donating methyl group is very labile and
      regenerates its QM with a half-life of approximately 5 h. The generality of these
      effects is demonstrated with a series of alternative quinone methide precursors
      (QMP) containing a variety of substituents attached at different positions with
      respect to the exocyclic methylene. The rates of nucleophilic addition to
      substituted QMs measured by laser flash photolysis similarly span 5 orders of
      magnitude with electron-rich species reacting most slowly and electron-deficient
      species reacting most quickly. The reversibility of QM reaction can now be
      predictably adjusted for any desired application.

PMID- 16953636
TI  - Practical approach for the stereoselective introduction of beta
      arabinofuranosides.
AB  - A practical approach for the stereoselective introduction of beta
      arabinofuranosides has been developed on the basis of locking an arabinosyl donor
      in a conformation in which nucleophilic attack from the beta face is favored. The
      new glycosyl donor was designed by analyzing optimized geometries of low-energy
      conformers of the arabinofuranosyl oxacarbenium ion. The Newman projection of the
      E(3) conformer indicated that nucleophilic attack from the alpha face is
      disfavored because an eclipsed H-2 will be encountered. On the other hand, an
      approach from the beta face was expected to be more favorable, because it will
      experience only staggered substituents. The arabinofuranosyl oxacarbenium ion
      could be locked in the E(3) conformation by employing a 3,5-O-di-tert-butylsilane
      protecting group, which places C-5 and O-3 in a pseudoequatorial orientation,
      resulting in a perfect chair conformation of the protecting group. The new
      glycosyl donor gave excellent beta selectivities in a range of glycosylations
      with glycosyl acceptors having primary and secondary alcohols. The attractiveness
      of the new methodology was demonstrated by the chemical synthesis of a fragment
      of arabinogalactan, which is an important constituent of the primary plant cell
      wall.

PMID- 16953637
TI  - Room-temperature biosynthesis of ferroelectric barium titanate nanoparticles.
AB  - The syntheses of inorganic materials by biological systems is characterized by
      processes that occur close to ambient temperatures, pressures, and neutral pH, as
      is exemplified by biosilicification and biomineralization processes in nature.
      Conversely, laboratory-based syntheses of oxide materials often require extremes
      of temperature and pressure. We have shown here the extracellular, room
      temperature biosynthesis of 4-5 nm ternary oxide nanoparticles such as barium
      titanate (BT) using a fungus-mediated approach. The tetragonality as well as a
      lowered Curie transition temperature in sub-10 nm particles was established, and
      the ferroelectricity in these particles was shown using Kelvin probe microscopy.

PMID- 16953638
TI  - Comparison of the specificity of interaction of cellular and viral zinc-binding
      domains with 2-mercaptobenzamide thioesters.
AB  - The interactions of two 2-mercaptobenzamide thioester compounds with six diverse
      zinc-binding domains (ZBDs) have been analyzed by UV/visible spectroscopy, NMR
      spectroscopy, and nucleic acid binding assays. These thioester compounds serve as
      useful tools for probing the intrinsic chemical stability of ZBDs that exist
      within a variety of cellular and viral proteins. In our studies, the classical
      (Cys(2)His(2)) zinc finger ZBDs, the interleaved RING like ZBDs of protein kinase
      C delta (Cys(2)HisCys and HisCys(3)), and the carboxyl-terminal (Cys(2)HisCys)
      ZBD of Mouse Mammary Tumor Virus nucleocapsid protein (MMTV NCp10) were resistant
      to reaction with the thioester compounds. In contrast, the thioester compounds
      were able to efficiently eject zinc from the amino-terminal (Cys(2)HisCys) ZBD of
      MMTV NCp10, a Cys(2)HisCys ZBD from Friend of GATA-1 (FOG-1), and from both
      Cys(4) ZBDs of GATA-1. In all cases, zinc ejection led to a loss of protein
      structure. Interestingly, GATA-1 was resistant to reaction with the thioester
      compounds when bound to its target DNA sequence. The electronic and steric
      screening was calculated for select ZBDs to further explore their reactivity.
      Based on these results, it appears that both first and second zinc-coordination
      shell interactions within ZBDs, as well as nucleic acid binding, play important
      roles in determining the chemical stability and reactivity of ZBDs. These studies
      not only provide information regarding the relative reactivity of cysteine
      residues within structural ZBDs but also are crucial for the design of future
      therapeutic agents that selectively target ZBDs, such as those that occur in the
      HIV-1 nucleocapsid protein.

PMID- 16953639
TI  - Large molecular assembly of amphotericin B formed in ergosterol-containing
      membrane evidenced by solid-state NMR of intramolecular bridged derivative.
AB  - Amphotericin B (AmB 1) is known to assemble and form an ion channel across
      biomembranes. We have recently reported that conformation-restricted derivatives
      of AmB 2-4 show different ergosterol preferences in ion-channel assays, which
      suggested that the orientation of the mycosamine strongly affects the sterol
      selectivity of AmB. The data allowed us to assume that compound 3 showing the
      highest selectivity would reflect the active conformation of AmB in the channel
      assembly. In this study, to gain further insight into the active conformation of
      AmB, we prepared a new intramolecular-bridged derivative 5, where the linker
      encompassed a hydrophilic glycine moiety. The derivative has almost equivalent
      ion-channel activity to those of AmB and 3. The antifungal activity of 5 compared
      with 3 improves significantly, possibly because the increasing hydrophilicity in
      the linker enhances the penetrability through the fungal cell wall. Conformation
      of 5 was well converged and very similar to that of 3, thus further supporting
      the notion that the conformations of these derivatives reproduce the active
      structure of AmB in the channel complex. Then we used the derivative to probe the
      mobility of AmB in the membrane by solid-state NMR. To measure dipolar couplings
      and chemical shift anisotropies, we incorporated [1-(13)C,(15)N]glycine into the
      linker. The results indicate that 5 is mostly immobilized in ergosterol
      containing DMPC bilayers, implying formation of large aggregates of 5. Meanwhile
      some fraction of 5 remains mobile in sterol-free DMPC bilayers, suggesting
      promotion of AmB aggregation by ergosterol.

PMID- 16953640
TI  - Discovery of a solid solution of enantiomers in a racemate-forming system by
      seeding.
AB  - A racemic liquid of opposite enantiomers usually crystallizes as a racemic
      compound (racemate), rarely as a conglomerate, and even more rarely as a solid
      solution. We discovered a Type II solid solution (mixed crystal) of the
      enantiomers of the chiral drug tazofelone (TZF) by seeding its racemic liquid
      with enantiomerically pure crystals (enantiomorphs). Without seeding, the racemic
      liquid crystallized as a racemic compound. The crystal structure of this solid
      solution resembles that of the enantiomorph but has static disorder arising from
      the random substitution of enantiomers. This solid solution is a kinetic product
      of crystallization made possible by its faster growth rate compared to that of
      the competing racemate (by 4- to 40-fold between 80 and 146 degrees C). The free
      energy of the solid solution continuously varies with the enantiomeric
      composition between those of the conglomerate and the racemates. The existence of
      the TZF solid solution explains the absence of eutectic melting between crystals
      of different enantiomeric compositions. The ability of TZF to simultaneously form
      racemate and solid solution originates from its conformational flexibility.
      Similar solid solutions of enantiomers may exist in other systems and may be
      discovered in similar ways. The study demonstrates the use of cross-nucleation
      for discovering and engineering crystalline materials to optimize physical
      properties.

PMID- 16953641
TI  - Edge-bridged Mo2Fe6S8 to pN-type Mo2Fe6S9 cluster conversion: structural fate of
      the attacking sulfide/selenide nucleophile.
AB  - Reaction of the edge-bridged double cubane cluster
      [(Tp)(2)M(2)Fe(6)S(8)(PEt(3))(4)] (1; Tp = hydrotris(pyrazolyl)borate(1-)) with
      hydrosulfide affords the clusters [(Tp)(2)M(2)Fe(6)S(9)(SH)(2)](3)(-)(,4)(-) (M =
      Mo (2), V), which have been established as the first structural (topological)
      analogues of the P(N) cluster of nitrogenase. The synthetic reaction is an
      example of core conversion, resulting in the transformation M(2)Fe(6)(mu(3)
      S)(6)(mu(4)-S)(2) (C(i)) --> M(2)Fe(6)(mu(2)-S)(2)(mu(3)-S)(6)(mu(6)-S)
      (C(2)(v)), the reaction pathway of which is unknown. The most prominent
      structural feature of P(N)-type clusters is the mu(6)-S atom, which bridges six
      iron atoms in two MFe(3)S(3) cuboidal halves of the cluster. The initial issue in
      core conversion is the origin of the mu(6)-S atom. Utilizing SeH(-) as a
      surrogate reactant for SH(-) in the system 1/SeH(-)/L(-) in acetonitrile, a
      series of selenide clusters [(Tp)(2)Mo(2)Fe(6)S(8)SeL(2)](3)(-) (L(-) = SH(-)
      (4), SeH(-) (5), EtS(-) (6), CN(-) (7)) was prepared. The electrospray mass
      spectra of 4 and 6 revealed inclusion of one Se atom in each cluster, and (1)H
      NMR spectra and crystallographic refinements of 4-7 indicated that this atom was
      disordered over the two mu(2)-S/Se positions. The clusters
      {[(Tp)(2)Mo(2)Fe(6)S(9)](mu(2)-S)}(2)(5)(-) (8) and
      {[(Tp)(2)Mo(2)Fe(6)S(8)Se](mu(2)-Se)}(2)(5)(-) (9) were prepared from 2 and 5,
      respectively, and shown to be isostructural. They consist of two P(N)-type
      cluster units bridged by two mu(2)-S or mu(2)-Se atoms. It is concluded that, in
      the preparation of 2, the probable structural fate of the attacking nucleophile
      is as a mu(2)-S atom, and that the mu(3)-S and mu(6)-S atoms of the product
      cluster derive from precursor cluster 1. Cluster fragmentation during P(N)-type
      cluster synthesis is unlikely.

PMID- 16953642
TI  - Chemical functionalization of boron-nitride nanotubes with NH3 and amino
      functional groups.
AB  - We have investigated properties of chemically modified boron nitride nanotubes
      (BNNTs) with NH(3) and four other amino functional groups (NH(2)CH(3),
      NH(2)CH(2)OCH(3), NH(2)CH(2)COOH, and NH(2)COOH) on the basis of density
      functional theory calculations. Unlike the case of carbon nanotubes, we found
      that NH(3) can be chemically adsorbed on top of the boron atom, with a charge
      transfer from NH(3) to the BNNT. The minimum-energy path calculation shows that a
      small energy barrier is encountered during the adsorption. Similarly, a small
      energy barrier (about 0.42 eV) is also involved in the desorption, suggesting
      that both adsorption and desorption can be realized even at room temperature. For
      chemically modified BNNTs with various amino functional groups, the adsorption
      energies are typically less than that of NH(3) on the BNNT. The trend of
      adsorption-energy change can be correlated with the trend of relative electron
      withdrawing or -donating capability of the amino functional groups. Overall, the
      chemical modification of BNNTs with the amino groups results in little changes in
      the electronic properties of BNNTs. However, the chemical reactivity of the BNNTs
      can be enhanced by the chemical modification with the amino group containing 
      COOH.

PMID- 16953643
TI  - Molecular structure and dynamics at the interfaces within bulk heterojunction
      materials for solar cells.
AB  - The molecular structures within the interfaces of the bulk heterojunction
      material comprising regioregular-poly(3-hexylthiophene-2,5-diyl), rrP3HT, and
      C(60) or its soluble derivative, [6,6]-phenyl-C(61)butyric acid methyl ester,
      PCBM, have been studied by one- and two-dimensional nuclear magnetic resonance
      (NMR). The local structure within the interface was inferred from chemical shift
      (CS) data obtained from composite films (CFs) fabricated at room temperature
      (PCBMCF-RT and C(60)CF-RT) and from CFs that had been subsequently annealed at
      150 degrees C for 30 min (PCBMCF-A150 and C(60)CF-150A). In PCBMCF-RT, the alkyl
      side chains of rrP3HT are close to the C(60) ball; C(60) is essentially 'wrapped'
      by the alkyl side chains. In PCBMCF-A150, the alkyl side chains self-assemble
      such that rrP3HT and PCBM are separated. The observation of well-defined
      splittings in the CS spectrum of the (13)C of C(60) in C(60)CF-A150 indicates a
      distortion from spherical symmetry. Measurements of the spin-lattice relaxation
      rate, 1/T(1), of C(60) imply local magnetic field fluctuations that arise from
      the dynamics of the C(60) distortion.

PMID- 16953644
TI  - Micelle density regulated by a reversible switch of protein secondary structure.
AB  - Protein secondary structures may exhibit reversible transitions that occur in an
      abrupt and controllable manner. In this report, we demonstrate that such
      transitions may be utilized in the design of a "smart" protein micellar system,
      in which a stimulus-induced change in protein structure triggers a rapid change
      in micelle compacticity and size. Specifically, recombinant DNA methods were used
      to prepare a protein triblock copolymer containing a central hydrophilic block
      and two hydrophobic end blocks derived from elastin-mimetic peptide sequences.
      Below the copolymer inverse transition temperature (T(t)), dilute solutions of
      this amphiphilic protein formed monodispersed micelles in a narrow range of R(H)
      of approximately 100 nm. When the the temperature was raised above T(t), an
      abrupt increase in micelle internal density was observed with a concomitant
      reduction in micelle size. This reversible change in micelle compacticity was
      triggered by helix-to-sheet protein folding transition. Significantly, these
      protein polymer-based micelles, which are rapidly responsive to environmental
      stimuli, establish a new mechanism for the design of controlled drug delivery
      vehicles.

PMID- 16953645
TI  - Why does perfluorination render bicyclo[2.2.0]hex-1(4)-ene stable toward
      dimerization? Calculations provide the answers.
AB  - B3LYP calculations with two different basis sets have been performed to
      understand why bicyclo[2.2.0]hex-1(4)-ene (1a) undergoes dimerization with
      DeltaH(++) = 11.5 kcal/mol, but dimerization of perfluorobicyclo[2.2.0]hex-1(4)
      ene (1b) has never been observed. The former reaction is computed to be
      exothermic by 37.2 kcal/mol, whereas the latter is calculated to be endothermic
      by 7.4 kcal/mol. The 44.6 kcal/mol difference between the enthalpies of these two
      reactions can be dissected into contributions of 24.5 kcal/mol for the difference
      between the enthalpies for forming diradical intermediates 2a and 2b and 20.1
      kcal/mol for cyclization of 2a and 2b to, respectively, 3a and 3b. The latter
      enthalpy difference is largely attributable to repulsions between the endo
      fluorines in the dimer, although the exo-fluorines also are found to contribute.
      The former enthalpy difference is attributable to the difference between the
      dissociation enthalpies of the pi bonds in 1a and 1b, which is shown to amount to
      16 +/- 1 kcal/mol. About 25% of the stronger pi bond in fluoroalkene 1b is found
      to be due to hyperconjugation of the eight C-F bonds in 1b with the filled pi
      orbital. However, the major contributor to the stronger pi bond in 1b is shown to
      be the unfavorable interaction that results when a pyramidalized radical center
      is syn to a C-F bond. Both of these effects, which contribute to the greater
      strength of the pi bond in 1b, relative to that in 1a, are analyzed and
      discussed.

PMID- 16953648
TI  - Methylphenidate and its isomers: their role in the treatment of attention-deficit
      hyperactivity disorder using a transdermal delivery system.
AB  - dl-threo-Methylphenidate is a highly efficacious drug for treating attention
      deficit hyperactivity disorder (ADHD) that is currently administered as immediate
      or controlled-release and osmotically controlled-released formulations. The drug
      exists as two enantiomers, d-threo-methylphenidate and l-threo-methylphenidate,
      with the former having been developed as a medication to treat ADHD in its own
      right. dl-threo-Methylphenidate undergoes enantioselective metabolism in the
      liver, which results in marked differences in the plasma concentrations of its
      isomers, depending on the route of administration and formulation. When dl-threo
      methylphenidate is orally administered, the plasma concentrations of d-threo
      methylphenidate are higher than those of l-threo-methylphenidate. However, with
      the recently developed methylphenidate transdermal system (MTS), 'first-pass'
      metabolism is circumvented and, as a consequence, plasma concentrations of d
      threo-methylphenidate are consistent with those produced by oral formulations,
      but the relative concentrations of l-threo-methylphenidate are much higher, i.e.
      50-60% of those of d-threo-methylphenidate. In this article, we review the
      pharmacokinetics and pharmacology of dl-threo-methylphenidate and its isomers to
      assess the extent to which their mechanism of action as noradrenaline
      (norepinephrine) and dopamine reuptake inhibitors is responsible for their
      efficacy and commonly occurring adverse effects. The major findings are that d
      threo-methylphenidate and l-threo-methylphenidate share the same pharmacological
      profile as the parent racemate, i.e. catecholamine-selective reuptake inhibition
      with higher potency against dopamine versus noradrenaline reuptake in vivo.
      However, d-threo-methylphenidate is approximately 10-fold more potent than the l
      isomer in this regard. For these drugs, their abilities not only to ameliorate
      the behavioural and cognitive dysfunctions in ADHD, but also to induce the common
      adverse effects of reduced appetite, nausea/vomiting and stomach ache, are almost
      certainly due to their ability to potentiate noradrenergic and/or dopaminergic
      function in the central and peripheral nervous systems. The sympathomimetic
      actions of ADHD drugs on cardiovascular function are currently an issue of
      concern. Since noradrenaline reuptake inhibition is the likely mediator for the
      effects of dl-threo-methylphenidate on blood pressure and heart rate, the more
      potent d-isomer will therefore be predominantly responsible. Motor and vocal tics
      are the other important adverse event to be considered in the treatment of ADHD.
      It is now accepted that tics are a frequently occurring behavioural manifestation
      of ADHD itself and the evidence for or against their exacerbation by treatment
      with dl-threo-methylphenidate or other stimulants remains highly contradictory.
      Focusing on the enantiomers of dl-threo-methylphenidate, it can be concluded that
      d-threo-methylphenidate, which is the more potent and abundant of the two
      isomers, is the major contributor of both efficacy and adverse effects,
      irrespective of the formulation or route of administration of the racemate.
      Moreover, for the oral, extended-release formulations of dl-threo
      methylphenidate, the d-isomer represents the only pharmacologically active moiety
      when these medications are used in the clinic. With the MTS, plasma
      concentrations of l-threo-methylphenidate are higher than are achieved using oral
      formulations, but even in this case, it is likely that the contribution of this
      enantiomer to the efficacy and adverse effects of the racemate is no greater than
      5-10% of the total.

PMID- 16953647
TI  - Buprenorphine-containing treatments: place in the management of opioid addiction.
AB  - Although the synthetic opioid buprenorphine has been available clinically for
      almost 30 years, its use has only recently become much more widespread for the
      treatment of opioid addiction. The pharmacodynamic and pharmacokinetic profiles
      of buprenorphine make it unique in the armamentarium of drugs for the treatment
      of opioid addiction. Buprenorphine has partial mu-opioid receptor agonist
      activity and is a kappa-opioid receptor antagonist; hence, it can substitute for
      other micro-opioid receptor agonists, yet is less apt to produce overdose
      reactions or dysphoria. On the other hand, buprenorphine can block the effects of
      opioids such as heroin (diamorphine) and morphine, and can even precipitate
      withdrawal in individuals physically dependent upon these drugs. Buprenorphine
      has significant sublingual bioavailability and a long half-life, making
      administration on a less than daily basis possible. Furthermore, its
      discontinuation is associated with only a mild withdrawal syndrome. Clinical
      trials have demonstrated that sublingual buprenorphine is effective in both
      maintenance therapy and detoxification of individuals addicted to opioids. The
      introduction of a sublingual formulation combining naloxone with buprenorphine
      further reduces the risk of diversion to illicit intravenous use. Because of its
      relative safety and lower risk of illegal diversion, buprenorphine has been made
      available in several countries for treating opioid addiction in the private
      office setting, greatly enhancing treatment options for this condition.

PMID- 16953649
TI  - Rivastigmine: in Parkinson's disease dementia.
AB  - Rivastigmine is a carbamate-type dual inhibitor of brain acetyl- and
      butyrylcholinesterases that has been evaluated in the symptomatic treatment of
      patients with mild to moderate dementia associated with idiopathic Parkinson's
      disease. Oral rivastigmine 3-12 mg/day for 24 weeks was significantly more
      effective than placebo in ameliorating cognitive and functional decline,
      including attentional deficits, in patients with Parkinson's disease dementia in
      a randomised, double-blind trial. The beneficial effects of rivastigmine observed
      in the double-blind trial were generally maintained in a 24-week extension of
      this study in which all patients received active treatment; placebo recipients
      who switched to rivastigmine also experienced improvements in their cognitive and
      functional symptoms at week 48. Rivastigmine appeared to be generally well
      tolerated, with the most common adverse events being mild to moderate in
      intensity and cholinergic in nature. Parkinsonian symptoms (mainly tremor) were
      more common in rivastigmine than placebo recipients.

PMID- 16953653
TI  - Rufinamide.
AB  - Rufinamide, a triazole derivative, reduces the recovery capacity of neuronal
      sodium channels after inactivation, limiting neuronal sodium-dependent action
      potential firing and mediating anticonvulsant effects. In children, adolescents
      and adults, adjunctive oral rufinamide was more effective than placebo in
      treating seizures associated with treatment-resistant Lennox-Gastaut syndrome in
      a well designed 16-week trial. Rufinamide recipients experienced significantly
      greater reductions from baseline than placebo recipients in the median frequency
      of total seizures and tonic-atonic seizures per 28 days and demonstrated
      improvements in seizure severity. Furthermore, these beneficial effects of
      rufinamide on seizure frequency were maintained throughout a subsequent 3-year,
      open-label extension study. Relative to placebo, adjunctive rufinamide
      significantly reduced the frequency of partial seizures per 28 days in adult
      patients with inadequately controlled partial seizures in two well designed
      trials of approximate, equals3 months duration, with a higher proportion of
      rufinamide recipients achieving a reduction of >or=50% in partial seizure
      frequency per 28 days. Rufinamide was generally well tolerated in patients with
      Lennox-Gastaut syndrome and in those with partial seizures, with adverse events
      being mostly mild or moderate in severity.

PMID- 16953657
TI  - Estimating the demand for a preventive HIV vaccine: why we need to do better.
      Reliable estimates would help in achieving several policy and advocacy
      objectives.

PMID- 16953656
TI  - Escitalopram: a review of its use in the management of anxiety disorders.
AB  - Escitalopram (Cipralex, Lexapro, Seroplex, Sipralexa), the therapeutically active
      S-enantiomer of racemic citalopram (RS-citalopram), is a potent and highly
      selective serotonin reuptake inhibitor. It is effective and generally well
      tolerated in the treatment of moderate to severe generalised anxiety disorder
      (GAD) or social anxiety disorder (SAD), panic disorder (with or without
      agoraphobia) as well as obsessive-compulsive disorder (OCD). Moreover,
      escitalopram is at least as effective as paroxetine for the treatment of GAD, SAD
      or OCD and appears to achieve a more rapid response than racemic citalopram in
      the management of panic disorder. Generally, it has a more favourable
      tolerability profile than paroxetine in terms of fewer discontinuation symptoms.
      In addition, a favourable pharmacokinetic profile permits once-daily
      administration of the drug. Additional comparative studies are required to
      definitively position escitalopram with respect to other SSRIs and venlafaxine.
      Nevertheless, available clinical data indicate that escitalopram is an effective
      first-line treatment option for the management of GAD, SAD, panic disorder and
      OCD.

PMID- 16953658
TI  - New rapid diagnostic tests for Neisseria meningitidis serogroups A, W135, C, and
      Y.
AB  - BACKGROUND: Outbreaks of meningococcal meningitis (meningitis caused by Neisseria
      meningitidis) are a major public health concern in the African "meningitis belt,"
      which includes 21 countries from Senegal to Ethiopia. Of the several species that
      can cause meningitis, N. meningitidis is the most important cause of epidemics in
      this region. In choosing the appropriate vaccine, accurate N. meningitidis
      serogroup determination is key. To this end, we developed and evaluated two
      duplex rapid diagnostic tests (RDTs) for detecting N. meningitidis polysaccharide
      (PS) antigens of several important serogroups. METHODS AND FINDINGS: Mouse
      monoclonal IgG antibodies against N. meningitidis PS A, W135/Y, Y, and C were
      used to develop two immunochromatography duplex RDTs, RDT1 (to detect serogroups
      A and W135/Y) and RDT2 (to detect serogroups C and Y). Standards for Reporting of
      Diagnostic Accuracy criteria were used to determine diagnostic accuracy of RDTs
      on reference strains and cerebrospinal fluid (CSF) samples using culture and PCR,
      respectively, as reference tests. The cutoffs were 10(5) cfu/ml for reference
      strains and 1 ng/ml for PS. Sensitivities and specificities were 100% for
      reference strains, and 93.8%-100% for CSF serogroups A, W135, and Y in CSF. For
      CSF serogroup A, the positive and negative likelihood ratios (+/- 95% confidence
      intervals [CIs]) were 31.867 (16.1-63.1) and 0.065 (0.04-0.104), respectively,
      and the diagnostic odds ratio (+/- 95% CI) was 492.9 (207.2-1,172.5). For CSF
      serogroups W135 and Y, the positive likelihood ratio was 159.6 (51.7-493.3) Both
      RDTs were equally reliable at 25 degrees C and 45 degrees C. CONCLUSIONS: These
      RDTs are important new bedside diagnostic tools for surveillance of meningococcus
      serogroups A and W135, the two serogroups that are responsible for major
      epidemics in Africa.

PMID- 16953659
TI  - Regulation of peripheral inflammation by spinal p38 MAP kinase in rats.
AB  - BACKGROUND: Somatic afferent input to the spinal cord from a peripheral
      inflammatory site can modulate the peripheral response. However, the
      intracellular signaling mechanisms in the spinal cord that regulate this linkage
      have not been defined. Previous studies suggest spinal cord p38 mitogen-activated
      protein (MAP) kinase and cytokines participate in nociceptive behavior. We
      therefore determined whether these pathways also regulate peripheral inflammation
      in rat adjuvant arthritis, which is a model of rheumatoid arthritis. METHODS AND
      FINDINGS: Selective blockade of spinal cord p38 MAP kinase by administering the
      p38 inhibitor SB203580 via intrathecal (IT) catheters in rats with adjuvant
      arthritis markedly suppressed paw swelling, inhibited synovial inflammation, and
      decreased radiographic evidence of joint destruction. The same dose of SB203580
      delivered systemically had no effect, indicating that the effect was mediated by
      local concentrations in the neural compartment. Evaluation of articular gene
      expression by quantitative real-time PCR showed that spinal p38 inhibition
      markedly decreased synovial interleukin-1 and -6 and matrix metalloproteinase
      (MMP3) gene expression. Activation of p38 required tumor necrosis factor alpha
      (TNFalpha) in the nervous system because IT etanercept (a TNF inhibitor) given
      during adjuvant arthritis blocked spinal p38 phosphorylation and reduced clinical
      signs of adjuvant arthritis. CONCLUSIONS: These data suggest that peripheral
      inflammation is sensed by the central nervous system (CNS), which subsequently
      activates stress-induced kinases in the spinal cord via a TNFalpha-dependent
      mechanism. Intracellular p38 MAP kinase signaling processes this information and
      profoundly modulates somatic inflammatory responses. Characterization of this
      mechanism could have clinical and basic research implications by supporting
      development of new treatments for arthritis and clarifying how the CNS regulates
      peripheral immune responses.

PMID- 16953660
TI  - Noncommunicable diseases and injuries in Latin America and the Caribbean: time
      for action.

PMID- 16953661
TI  - Promoting translational and clinical science: the critical role of medical
      schools and teaching hospitals.

PMID- 16953662
TI  - Neonatal imitation in rhesus macaques.
AB  - The emergence of social behaviors early in life is likely crucial for the
      development of mother-infant relationships. Some of these behaviors, such as the
      capacity of neonates to imitate adult facial movements, were previously thought
      to be limited to humans and perhaps the ape lineage. Here we report the
      behavioral responses of infant rhesus macaques (Macaca mulatta) to the following
      human facial and hand gestures: lip smacking, tongue protrusion, mouth opening,
      hand opening, and opening and closing of eyes (control condition). In the third
      day of life, infant macaques imitate lip smacking and tongue protrusion. On the
      first day of life, the model's mouth openings elicited a similar matched behavior
      (lip smacking) in the infants. These imitative responses are present at an early
      stage of development, but they are apparently confined to a narrow temporal
      window. Because lip smacking is a core gesture in face-to-face interactions in
      macaques, neonatal imitation may serve to tune infants' affiliative responses to
      the social world. Our findings provide a quantitative description of neonatal
      imitation in a nonhuman primate species and suggest that these imitative
      capacities, contrary to what was previously thought, are not unique to the ape
      and human lineage. We suggest that their evolutionary origins may be traced to
      affiliative gestures with communicative functions.

PMID- 16953663
TI  - Levels of gamma-H2AX Foci after low-dose-rate irradiation reveal a DNA DSB
      rejoining defect in cells from human ATM heterozygotes in two at families and in
      another apparently normal individual.
AB  - We have investigated the use of the gamma-H2AX assay, reflecting the presence of
      DNA double-strand breaks, as a possible means for identifying individuals who are
      mildly hypersensitive to ionizing radiation, such as some ATM heterozygotes. We
      compared levels of gamma-H2AX foci after irradiation in cells from six apparently
      normal individuals as well as from individuals from two separate AT families
      including the proband, mother, father and three unaffected siblings in each
      family. After a 1-Gy single acute (high-dose-rate) gamma-ray dose delivered to
      noncycling contact-inhibited monolayers of cells, clear differences were seen
      between samples from normal individuals (ATM(+/+)) and probands (ATM(-/-)) at
      nearly all sampling times after irradiation, but no clear distinctions were seen
      for cells from normal compared to obligate heterozygotes (ATM(+/-)). In contrast,
      after 24 h of continuous irradiation at a dose rate of 10 cGy/h, appreciable
      differences in numbers of foci per cell were observed for cells from individuals
      for all the known ATM genotypes compared with controls. Four unaffected siblings
      had mean numbers of foci per cell similar to that for the obligate heterozygotes,
      whereas the other two had mean values similar to that for normal controls. We
      determined independently that those siblings with mean numbers of foci per cell
      in the range of ATM heterozygotes carried the mutant allele, while both siblings
      with a normal number of foci per cell after irradiation had normal alleles. A
      more limited set of experiments using lymphoblastoid cell strains in the low-dose
      rate assay also revealed distinct differences for normal compared to ATM
      heterozygotes from the same families and opens the possibility of using
      peripheral blood lymphocytes as a more suitable material for an assay to detect
      mild hypersensitivities to radiation among individuals.

PMID- 16953664
TI  - Overexpression of MDR1 using a retroviral vector differentially regulates genes
      involved in detoxification and apoptosis and confers radioprotection.
AB  - Overexpression of P-glycoprotein (P-gp), the product of the MDR1 (multidrug
      resistance 1) gene, might complement chemotherapy and radiotherapy in the
      treatment of tumors. However, for safety and mechanistic reasons, it is important
      to know whether MDR1 overexpression influences the expression of other genes.
      Therefore, we analyzed differential gene expression in cells of the human
      lymphoblast cell line TK6 retrovirally transduced with MDR1 using the GeneChip
      Human Genome U133 Plus2.0 (Affymetrix). Sixty-one annotated genes showed a
      significant change in expression (P < 10(-4)) in MDR1-overexpressing cells
      compared to untransduced cells and cells transduced with a control virus
      expressing the neomycin phosphotransferase gene. Several genes coding for
      proteins involved in detoxification and exocytosis showed approximately 1.4- 4
      fold increases in transcript levels (e.g. ALDH1A, UNC13). Additionally, pro
      apoptosis genes were down-regulated (e.g. twofold for CASP1, 2.5-fold for NALP7)
      with concomitant increased expression of the potential anti-apoptosis gene AKT3.
      In functional assays the influence of MDR1 overexpression on apoptosis signaling
      was further corroborated by showing reduced rates of apoptosis in response to
      irradiation in TK6 cells transduced with MDR1. In conclusion, the resistant
      phenotype of MDR1-mediated P-gp-overexpressing cells is associated with
      differential expression of genes coding for metabolic and apoptosis-related
      proteins. These results have important implications for understanding the
      mechanisms by which MDR1 gene therapy can protect normal tissues from radiation-
      or chemotherapy-induced damage during tumor treatment.

PMID- 16953665
TI  - Activation of antioxidative enzymes induced by low-dose-rate whole-body gamma
      irradiation: adaptive response in terms of initial DNA damage.
AB  - An adaptive response induced by long-term low-dose-rate irradiation in mice was
      evaluated in terms of the amount of DNA damage in the spleen analyzed by a comet
      assay. C57BL/ 6N female mice were irradiated with 0.5 Gy of (137)Cs gamma rays at
      1.2 mGy/h; thereafter, a challenge dose (0.4, 0.8 or 1.6 Gy) at a high dose rate
      was given. Less DNA damage was observed in the spleen cells of preirradiated mice
      than in those of mice that received the challenge dose only; an adaptive response
      in terms of DNA damage was induced by long-term low-dose-rate irradiation in
      mice. The gene expression of catalase and Mn-SOD was significantly increased in
      the spleen after 23 days of the low-dose-rate radiation (0.5 Gy). In addition,
      the enzymatic activity of catalase corresponded to the gene expression level; the
      increase in the activity was observed at day 23 (0.5 Gy). These results suggested
      that an enhancement of the antioxidative capacities played an important role in
      the reduction of initial DNA damage by low-dose-rate radiation.

PMID- 16953666
TI  - Calcium fluxes modulate the radiation-induced bystander responses in targeted
      glioma and fibroblast cells.
AB  - Bystander responses have been reported to be a major determinant of the response
      of cells to radiation exposure at low doses, including those of relevance to
      therapy. This study investigated the role of changes in calcium levels in
      bystander responses leading to chromosomal damage in nonirradiated T98G glioma
      cells and AG01522 fibroblasts that had been either exposed to conditioned medium
      from irradiated cells or co-cultured with a population where a fraction of cells
      were individually targeted through the nucleus or cytoplasm with a precise number
      of microbeam helium-3 particles. After the recipient cells were treated with
      conditioned medium from T98G or AG01522 cells that had been irradiated through
      either nucleus or cytoplasm, rapid calcium fluxes were monitored in the
      nonirradiated recipient cells. Their characteristics were dependent on the source
      of the conditioned medium but had no dependence on radiation dose. When recipient
      cells were co-cultured with an irradiated population of either T98G or AG01522
      cells, micronuclei were induced in the nonirradiated cells, but this response was
      eliminated by treating the cells with calcicludine (CaC), a potent blocker of
      Ca(2+) channels. Moreover, both the calcium fluxes and the bystander effect were
      inhibited when the irradiated T98G cells were treated with aminoguanidine, an
      inhibitor of nitric oxide synthase (NOS), and when the irradiated AG01522 cells
      were treated with DMSO, a scavenger of reactive oxygen species (ROS), which
      indicates that NO and ROS were involved in the bystander responses generated from
      irradiated T98G and AG01522 cells, respectively. Our findings indicate that
      calcium signaling may be an early response in radiation-induced bystander effects
      leading to chromosome damage.

PMID- 16953667
TI  - Proton-HZE-particle sequential dual-beam exposures increase anchorage-independent
      growth frequencies in primary human fibroblasts.
AB  - The radiation field in deep space contains high levels of high-energy protons and
      substantially lower levels of high-atomic-number, high-energy (HZE) particles.
      Calculations indicate that cellular nuclei of human space travelers will be hit
      during a 3-year Mars mission by approximately 400 protons and approximately 0.4
      HZE particles. Thus most cells in astronauts will be hit by a proton(s) before
      being hit by an HZE particle. To investigate effects of dual ion irradiations on
      human cells, we irradiated primary human neonatal fibroblasts with protons (1
      GeV/nucleon, 20 cGy) followed from 2.5 min to 48 h later by iron or titanium ions
      (1 GeV/nucleon, 20 cGy) and then measured clonogenic survival and frequency of
      anchorage-independent growth. This frequency depends on the interval between
      hydrogen- and iron-ion irradiation, with a critical window between 2.5 min and 1
      h producing about three times more anchorage-independent colonies per survivor
      than expected from simple addition of the two ions separately. The hydrogen
      titanium-ion dual-beam irradiation produced similar increases that persisted to
      approximately 6 h. At longer intervals, anchorage-independent growth frequencies
      were similar to those expected for additivity. However, irradiation of cells with
      either an iron or a titanium particle first followed by protons produced only
      additive levels.

PMID- 16953668
TI  - Late effects of radiation on the central nervous system: role of vascular
      endothelial damage and glial stem cell survival.
AB  - Selective irradiation of the vasculature of the rat spinal cord was used in this
      study, which was designed specifically to address the question as to whether it
      is the endothelial cell or the glial progenitor cell that is the target
      responsible for late white matter necrosis in the CNS. Selective irradiation of
      the vascular endothelium was achieved by the intraperitoneal (ip) administration
      of a boron compound known as BSH (Na(2)B(12)H(11)SH), followed by local
      irradiation with thermal neutrons. The blood-brain barrier is known to exclude
      BSH from the CNS parenchyma. Thirty minutes after the ip injection of BSH, the
      boron concentration in blood was 100 microg (10)B/ g, while that in the CNS
      parenchyma was below the detection limit of the boron analysis system, <1 microg
      (10)B/g. An ex vivo clonogenic assay of the O2A (oligodendrocyte-type 2
      astrocyte) glial progenitor cell survival was performed 1 week after irradiation
      and at various times during the latent period before white matter necrosis in the
      spinal cord resulted in myelopathy. One week after 4.5 Gy of thermal neutron
      irradiation alone (approximately one-third of the dose required to produce a 50%
      incidence of radiation myelopathy), the average glial progenitor cell surviving
      fraction was 0.03. The surviving fraction of glial progenitor cells after a
      thermal neutron irradiation with BSH for a comparable effect was 0.46. The high
      level of glial progenitor cell survival after irradiation in the presence of BSH
      clearly reflects the lower dose delivered to the parenchyma due to the complete
      exclusion of BSH by the blood-brain barrier. The intermediate response of glial
      progenitor cells after irradiation with thermal neutrons in the presence of a
      boron compound known as BPA (p-dihydroxyboryl-phenylalanine), again for a dose
      that represents one-third the ED(50) for radiation-induced myelopathy, reflects
      the differential partition of boron-10 between blood and CNS parenchyma for this
      compound, which crosses the blood-brain barrier, at the time of irradiation. The
      large differences in glial progenitor survival seen 1 week after irradiation were
      also maintained during the 4-5-month latent period before the development of
      radiation myelopathy, due to selective white matter necrosis, after irradiation
      with doses that would produce a high incidence of radiation myelopathy. Glial
      progenitor survival was similar to control values at 100 days after irradiation
      with a dose of thermal neutrons in the presence of BSH, significantly greater
      than the ED(100), shortly before the normal time of onset of myelopathy. In
      contrast, glial progenitor survival was less than 1% of control levels after
      irradiation with 15 Gy of thermal neutrons alone. This dose of thermal neutrons
      represents the approximate ED(90-100) for myelopathy. The response to irradiation
      with an equivalent dose of X rays (ED(90): 23 Gy) was intermediate between these
      extremes as it was to thermal neutrons in the presence of BPA at a slightly lower
      dose equivalent to the approximate ED(60) for radiation myelopathy. The
      conclusions from these studies, performed at dose levels approximately iso
      effective for radiation-induced myelopathy as a consequence of white matter
      necrosis, were that the large differences observed in glial progenitor survival
      were directly related to the dose distribution in the parenchyma. These
      observations clearly indicate the relative importance of the dose to the vascular
      endothelium as the primary event leading to white matter necrosis.

PMID- 16953669
TI  - Use of flt3 ligand to evaluate residual hematopoiesis after heterogeneous
      irradiation in mice.
AB  - We evaluated the possibility of using plasma Flt3 ligand (FL) concentration as a
      biological indicator of bone marrow function after heterogeneous irradiation.
      Mice were irradiated with 4, 7.5 or 11 Gy with 25, 50, 75 or 100% of the bone
      marrow in the field of irradiation. This model of irradiation resulted in graded
      and controlled damage to the bone marrow. Mice exhibited a pancytopenia
      correlated with both the radiation dose and the percentage of bone marrow
      irradiated. The FL concentration in the blood increased with the severity of bone
      marrow aplasia. Nonlinear regression analysis showed that the FL concentration
      was strongly correlated with the total number of residual colony-forming cells 3
      days after irradiation, allowing a precise estimate of residual hematopoiesis.
      Moreover, the FL concentration on day 3 postirradiation was correlated with the
      duration and severity of subsequent pancytopenia, suggesting that variations in
      FL concentrations might be used as a predictive indicator of bone marrow aplasia,
      especially by the use of linear regression equations describing these
      correlations. Our results provide a rationale for the use of FL concentration as
      a biological indicator of residual hematopoiesis after heterogeneous irradiation.

PMID- 16953670
TI  - Measurements of partial oxygen pressure pO2 using the OxyLite system in R3327-AT
      tumors under isoflurane anesthesia.
AB  - The presence of oxygen-deficient tumor cells is a critical issue in cancer
      therapy. To identify tumor hypoxia, tissue partial oxygen pressure (pO2) can be
      measured directly. The OxyLite system allows determination of pO2 in tumors and
      permits continuous measurements of pO2 at a fixed point. In this study, this
      system was used to continuously measure pO2 in R3327-AT tumors in animals
      anesthetized with isoflurane. In addition, continuous pO2 measurement was
      performed in the muscle in non-tumor-bearing animals. In animals breathing
      isoflurane balanced by air, tumor pO2 at fixed positions decreased rapidly within
      1-2 min of probe positioning but remained stable thereafter. In animals breathing
      isoflurane balanced by pure oxygen, tumor pO2 was higher and remained high. We
      also measured pO2 values at multiple positions in R3327-AT tumors of various
      sizes, with anesthetized animals breathing either air or pure oxygen. Our data
      showed that the frequency of pO2 measurements below 2.5 or 5.0 mmHg was
      significantly higher in animals breathing air than in animals breathing pure
      oxygen. Measurements in different-sized tumors showed that the mean pO2 value
      decreased as tumor volume increased, with the largest change occurring between
      tumor volumes of 100 and 200 mm3. Our data demonstrate that the OxyLite system,
      when used with isoflurane anesthesia, is a valuable tool in the study of tumor
      hypoxia.

PMID- 16953671
TI  - Microarray comparative genomic hybridization reveals genome-wide patterns of DNA
      gains and losses in post-Chernobyl thyroid cancer.
AB  - Genetic gains and losses resulting from DNA strand breakage by ionizing radiation
      have been demonstrated in vitro and suspected in radiation-associated thyroid
      cancer. We hypothesized that copy number deviations might be more prevalent,
      and/or occur in genomic patterns, in tumors associated with presumptive DNA
      strand breakage from radiation exposure than in their spontaneous counterparts.
      We used cDNA microarray-based comparative genome hybridization to obtain genome
      wide, high-resolution copy number profiles at 14,573 genomic loci in 23 post
      Chernobyl and 20 spontaneous thyroid cancers. The prevalence of DNA gains in
      tumors from cases in exposed individuals was two- to fourfold higher than for
      cases in unexposed individuals and up to 10-fold higher for the subset of
      recurrent gains. DNA losses for all cases were low and more prevalent in
      spontaneous cases. We identified unique patterns of copy variation (mostly gains)
      that depended on a history of radiation exposure. Exposed cases, especially the
      young, harbored more recurrent gains that covered more of the genome. The largest
      regions, spanning 1.2 to 4.9 Mbp, were located at 1p36.32-.33, 2p23.2-.3, 3p21.1
      .31, 6p22.1-.2, 7q36.1, 8q24.3, 9q34.11, 9q34.3, 11p15.5, 11q13.2-12.3, 14q32.33,
      16p13.3, 16p11.2, 16q21-q12.2, 17q25.1, 19p13.31-qter, 22q11.21 and 22q13.2. Copy
      number changes, particularly gains, in post-Chernobyl thyroid cancer are
      influenced by radiation exposure and age at exposure, in addition to the
      neoplastic process.

PMID- 16953672
TI  - Comparative study of cell cycle kinetics and induction of apoptosis or necrosis
      after exposure of human Mono Mac 6 cells to radiofrequency radiation.
AB  - The possible harmful effects of radiofrequency electromagnetic fields (RF EMFs)
      are controversial. We have used human Mono Mac 6 cells to investigate the
      influence of RF EMFs in vitro on cell cycle alterations and BrdU uptake, as well
      as the induction of apoptosis and necrosis in human Mono Mac 6 cells, using flow
      cytometry after exposure to a 1,800 MHz, 2 W/kg specific absorption rate (SAR),
      GSM-DTX signal for 12 h. No statistically significant differences in the
      induction of apoptosis or necrosis, cell cycle kinetics, or BrdU uptake were
      detected after RF EMF exposure compared to sham or incubator controls. However,
      in the positive control cells treated with gliotoxin and PMA (phorbol 12
      myristate-13 acetate), a significant increase in apoptotic and necrotic cells was
      seen. Cell cycle analysis or BrdU incorporation for 72 h showed no differences
      between RF EMF- or sham-exposed cells, whereas PMA treatment induced a
      significant accumulation of cells in G(0)/G(1)-phase and a reduction in S-phase
      cells. RF EMF radiation did not induce cell cycle alterations or changes in BrdU
      incorporation or induce apoptosis and necrosis in Mono Mac 6 cells under the
      exposure conditions used.

PMID- 16953673
TI  - Analytical functions to predict cosmic-ray neutron spectra in the atmosphere.
AB  - Estimation of cosmic-ray neutron spectra in the atmosphere has been an essential
      issue in the evaluation of the aircrew doses and the soft-error rates of
      semiconductor devices. We therefore performed Monte Carlo simulations for
      estimating neutron spectra using the PHITS code in adopting the nuclear data
      library JENDL-High-Energy file. Excellent agreements were observed between the
      calculated and measured spectra for a wide altitude range even at the ground
      level. Based on a comprehensive analysis of the simulation results, we propose
      analytical functions that can predict the cosmic-ray neutron spectra for any
      location in the atmosphere at altitudes below 20 km, considering the influences
      of local geometries such as ground and aircraft on the spectra. The accuracy of
      the analytical functions was well verified by various experimental data.

PMID- 16953674
TI  - Meloxicam, a cyclooxygenase 2 inhibitor, supports hematopoietic recovery in gamma
      irradiated mice.
AB  - Meloxicam, a selective inhibitor of cyclooxygenase 2, a nonsteroidal anti
      inflammatory drug with an improved side-effects profile in terms of
      gastrointestinal toxicity, has been found to stimulate hematopoiesis in whole
      body gamma-irradiated mice. A distinct corroboration of this positive action of
      meloxicam is an enhancement of the recovery of hematopoietic progenitor cells
      committed to granulocyte-macrophage and erythroid development, which has been
      demonstrated in sublethally irradiated animals treated with meloxicam at a dose
      of 20 mg/kg administered intraperitoneally either singly 1 h before irradiation
      or repeatedly after radiation exposure. The results suggest that meloxicam can be
      added to the list of biological response modifiers that can be used in the
      treatment of hematopoietic damage induced by ionizing radiation.

PMID- 16953676
TI  - Calcifying fibrous pseudotumor of the myocardium.
AB  - Calcifying fibrous pseudotumor is an uncommon tumor first described in 1988 as a
      childhood fibrous tumor with psammoma bodies. The typical pathological findings
      are those of a densely collagenized fibrous tumor with psammomatous and
      dystrophic calcification accompanied by a lymphoplasmacytic infiltrate. To date
      these tumors are reported in subcutaneous and deep soft tissues of the
      extremities and trunk, groin, scrotum, pleura, mediastinum, paratracheal region,
      peritoneum, neck, mesentery, omentum, serosa, lung, bone, and gallbladder. We
      describe a 17-year-old girl with a myocardial calcifying fibrous tumor, and we
      review the English literature.

PMID- 16953677
TI  - Bronchial atresia is common to extralobar sequestration, intralobar
      sequestration, congenital cystic adenomatoid malformation, and lobar emphysema.
AB  - Congenital cystic adenomatoid malformation (CCAM), intralobar sequestration
      (ILS), extralobar sequestration (ELS), and lobar emphysema (LE) are well-accepted
      entities; however, certain findings are common to all, particularly the
      parenchymal maldevelopment characterizing CCAM. Isolated reports have described
      bronchial atresia (BA) in some specimens in all 4 entities, but this finding has
      not been evaluated in a prospective manner. With the aid of a dissecting
      microscope, we prospectively examined 47 lung specimens resected during the past
      4 years and submitted with the clinical impression of ELS (n=11), ILS (n=11),
      CCAM (n=20), LE (n=4), and airway-esophageal communication (n=1). Most lesions
      were detected by prenatal ultrasound and were resected during infancy. The
      clinical impression and pathologic findings were compared. Pathologic examination
      revealed atresia of a lobar, segmental, or subsegmental bronchus in 100% of ELS,
      82% of ILS, 70% of CCAM, and 50% of LE (those clinically recognized to have BA or
      minor CCAM) cases. Parenchymal maldevelopment that characterizes CCAM was present
      in 100% of CCAM cases (as expected by definition) as well as in 91% of ELS, 91%
      of ILS, and 50% of LE (those with BA) cases. Bronchial atresia is present in all
      ELS, most ILS and CCAM, and some LE cases, and its detection is greatly enhanced
      with the dissecting microscope. Bronchial atresia and CCAM nearly always coexist.
      It may be that both have the same etiopathogenesis with anatomic differences
      accounted for by aberrant genetic programs or other insults, perhaps modified by
      time of onset or duration.

PMID- 16953678
TI  - The autopsy in pediatrics and pediatric oncology: a single-institution
      experience.
AB  - Autopsy rates and clinicopathologic correlations for pediatric autopsies and the
      subgroup of pediatric oncology autopsies in a large teaching hospital were
      studied to evaluate the utility of autopsy in these populations. Autopsy records
      of the University of North Carolina hospitals from 1982 to 2001 were reviewed for
      all patients less than 18 years of age. Autopsies performed during 1982 to 1991
      (decade 1) were compared to those from 1992 to 2001 (decade 2) with respect to
      absolute numbers of autopsy and rates of unexpected postmortem diagnoses.
      Postmortem diagnostic discrepancies were subclassified into major and minor
      categories. The mean number of autopsies per year for decade 1 was 110+/-24.5,
      compared with 77.5+/-40.9 for decade 2 (P<0.001), a change largely due to a
      decline in fetal/perinatal (patients<7 days of age) autopsies. Of 533 pediatric
      autopsies, 43 were in patients with a primary diagnosis of a neoplasia. At least
      one antemortem misdiagnosis and/or clinically occult process was identified in
      20.5% of all pediatric autopsy cases, and in 25.6% of pediatric oncology cases.
      These rates did not change significantly over time. In 10 of 43 pediatric
      oncology cases (23.3%), autopsies provided diagnostic information that was
      previously unknown to the clinicians. Three of these patients died shortly after
      presentation. Although autopsy rates for fetal/perinatal cases have declined,
      those for non-perinatal and pediatric oncology patients remain stable. Autopsy
      continues to provide diagnostic information that is unknown during the antemortem
      period, and remains a valuable tool for pediatricians and pediatric oncologists.

PMID- 16953679
TI  - Conjunctival Splendore-Hoeppli phenomenon in a 3-year-old child.
AB  - A case of benign granulomas of the conjunctiva in a 3-year-old girl is reported.
      Histologic features of the excised conjunctival lesions were consistent with
      Splendore-Hoeppli phenomenon. This phenomenon is thought to be a granulomatous
      reaction to an antigen-antibody precipitate related to parasites or fungi. No
      causative agent is identified in our patient. Immunohistochemical analysis showed
      no immunoreactivity for immunoglobulin G (IgG), IgM, IgA, or the C3 component of
      the complement. We propose that the presence of small amelanotic nodular
      conjunctival tumors should arouse suspicion related to the Splendore-Hoeppli
      phenomenon even in early childhood.

PMID- 16953681
TI  - Founders of pediatric pathology: Marie Valdes-Dapena.

PMID- 16953682
TI  - Syringocystadenoma papilliferum: a rare breast tumor in a young boy.
AB  - Syringocystadenoma papilliferum of the breast is extremely rare in children.
      However, some occasional cases have been diagnosed in females. This report
      documents a case of syringocystadenoma papilliferum occurring in a healthy 4-year
      old male. Histopathologically, this tumor, located deep in the dermis, was
      characterized by the presence of papillary projections extending into the lumen
      of epithelial cystic invaginations in a background of dense fibrous tissue. The
      papillary projections and the duct-like structures were lined by an inner
      columnar epithelium, which demonstrated luminal apical decapitation secretion,
      and had an outer layer of smaller cuboidal cells. These findings support apocrine
      differentiation in this case. A fairly dense mononuclear infiltrate in the stroma
      of the tumor, especially in the papillary projections, was also present. Although
      syringocystadenoma papilliferum is rare in children, it should not be summarily
      ruled out during examinations of masses found in the pediatric male breast. It is
      important to recognize this unusual location of the tumor so that a prompt
      diagnosis, based on histopathology and surgical excision, can be proposed.

PMID- 16953683
TI  - Chorion nodosum: a placental feature of the severe early amnion rupture sequence.
AB  - A lesion of placental membranes and/or chorionic disc mesenchyme found in 4 of 13
      cases of the limb-body wall complex (LBWC) and in 1 case of term extraamniotic
      pregnancy, named chorion nodosum (ChN), is described. All five ChN cases were
      associated with amniotic bands. Although grossly inapparent and histologically
      superficially similar to amnion nodosum, ChN is a distinct flat lesion located in
      the chorion denuded of amnion, occurring in different clinical settings, and most
      probably having a different pathogenesis, because it has bimodal gestational age
      distribution and occurs earlier in pregnancy when associated with LBWC, and only
      in the LBWC cases associated with amniotic bands. Therefore, not only
      oligohydramnios but also other factors involved in etiopathogenesis of LBWC are
      most probably operative in ChN, such as early vascular disruption, direct contact
      of the chorion denuded of amnion with fetal body, or a metabolic defect of fetal
      epidermis and amnionic epithelium. Prolonged severe oligohydramnios most probably
      plays main role in the pathogenesis of ChN in term extraamniotic pregnancy.

PMID- 16953684
TI  - Parents' ethnic-racial socialization practices: a review of research and
      directions for future study.
AB  - Recently, there has been an emergence of literature on the mechanisms through
      which parents transmit information, values, and perspectives about ethnicity and
      race to their children, commonly referred to as racial or ethnic socialization.
      This literature has sought to document the nature of such socialization, its
      antecedents in parents' and children's characteristics and experiences, and its
      consequences for children's well-being and development. In this article, the
      authors integrate and synthesize what is known about racial and ethnic
      socialization on the basis of current empirical research, examining studies
      concerning its nature and frequency; its child, parent, and ecological
      predictors; and its consequences for children's development, including ethnic
      identity, self-esteem, coping with discrimination, academic achievement, and
      psychosocial well-being. The authors also discuss conceptual and methodological
      limitations of the literature and suggest directions for future research.

PMID- 16953685
TI  - Prosocial behavior from early to middle childhood: genetic and environmental
      influences on stability and change.
AB  - Prosocial behavior is important for the functioning of society. This study
      investigates the extent to which environment shared by family members, nonshared
      environment, and genetics account for children's prosocial behavior. The
      prosocial behavior of twins (9,424 pairs) was rated by their parents at the ages
      of 2, 3, 4, and 7 and by their teachers at age 7. For parent ratings, shared
      environmental effects decreased from .47 on average at age 2 to .03 at age 7, and
      genetic effects increased from .32 on average to .61. The finding of weak shared
      environmental effects and large heritability at age 7 was largely confirmed
      through the use of teacher ratings. Using longitudinal genetic analyses, the
      authors conclude that genetic effects account for both change and continuity in
      prosocial behavior and nonshared environment contributes mainly to change.

PMID- 16953686
TI  - Gender differences in the age-changing relationship between instrumentality and
      family contact in emerging adulthood.
AB  - Data from the Children in the Community Transitions Study were used to examine
      gender differences in the impact of family contact on the development of finance
      and romance instrumentality from ages 17 to 27 years. Family contact decreased
      among both men and women across emerging adulthood, although it decreased more
      rapidly in men than in women. Both finance and romance instrumentality increased
      for men and women across emerging adulthood. The growth rate did not differ
      between men and women in either domain, although men tended to be characterized
      by higher levels of instrumentality than women. There were noteworthy gender
      differences in the impact of family contact on the development of
      instrumentality. At age 17, family contact was negatively associated with
      instrumentality for both men and women; at age 27, the impact of family contact
      on instrumentality was less negative for women and was positive for men.

PMID- 16953687
TI  - Adult age differences in autobiographical reasoning in narratives.
AB  - Two studies examined age differences in autobiographical reasoning within
      narratives about personal experiences. In Study 1 (n=63), people completed brief
      interviews about turning points and crises in their lives. Older participants
      were more likely to narrate crises in ways that connected the experience to the
      speaker's sense of self, that is, to show autobiographical reasoning. This
      increase was primarily evident in young adulthood and midlife. In Study 2
      (n=115), adults provided written narratives about heterogeneous autobiographical
      experiences. Age was associated with linear increases in the likelihood of
      autobiographical reasoning. The results are discussed in terms of narrative
      approaches to self-development across the life span.

PMID- 16953688
TI  - Understanding of emotional experience in autism: insights from the personal
      accounts of high-functioning children with autism.
AB  - In this study, the authors investigate emotional understanding in autism through
      a discourse analytic framework to provide a window into children's strategies for
      interpreting emotional versus nonemotional encounters and consider the
      implications for the mechanisms underlying emotional understanding in typical
      development. Accounts were analyzed for thematic content and discourse structure.
      Whereas high-functioning children with autism were able to discuss contextually
      appropriate accounts of simple emotions, their strategies for interpreting all
      types of emotional (but not nonemotional) experiences differed from those used by
      typically developing children. High-functioning children with autism were less
      inclined to organize their emotional accounts in personalized causal-explanatory
      frameworks and displayed a tendency to describe visually salient elements of
      experiences seldom observed among comparison children. Findings suggest that
      children with autism possess less coherent representations of emotional
      experiences and use alternative strategies for interpreting emotionally evocative
      encounters. Discussion focuses on the significance of these findings for
      informing the nature of emotional dysfunction in autism as well as implications
      for theories of emotional understanding in typical development.

PMID- 16953689
TI  - Growth in temperament and parenting as predictors of adjustment during children's
      transition to adolescence.
AB  - The author examined relations among demographic risk (income, maternal education,
      single-parent status), growth in temperament (fear, irritability, effortful
      control), and parenting (rejection, inconsistent discipline) across 3 years and
      the prediction of children's adjustment problems in a community sample (N=190;
      ages 8-12 years at Time 1). Family income was related to higher initial levels of
      fear, irritability, rejection, and inconsistency and lower effortful control but
      was not related to changes in these variables. Higher initial rejection predicted
      increases in child fear and irritability. Higher initial fear predicted decreases
      in rejection and inconsistency. Higher initial irritability predicted increases
      in inconsistency, and higher initial effortful control predicted decreases in
      rejection. When growth of parenting and temperament were considered
      simultaneously, increases in effortful control and decreases in fear and
      irritability predicted lower Time 3 internalizing and externalizing problems.
      Increases in rejection and inconsistent discipline predicted higher Time 3
      externalizing, although sometimes the effect appeared to be indirect through
      temperament. The findings suggest that temperament and parenting predict changes
      in each other and predict adjustment during the transition to adolescence.

PMID- 16953690
TI  - Mutually responsive orientation between parents and their young children: toward
      methodological advances in the science of relationships.
AB  - The authors captured mother-child and father-child relationships when children
      were 7 and 15 months old by coding 4 explicitly dyadic components of mutually
      responsive orientation (MRO): coordinated routines, harmonious communication,
      mutual cooperation, and emotional ambiance. These components were coded in 102
      families in naturalistic contexts at home and in the laboratory. Using
      confirmatory factor analytic methods, the authors demonstrated that MRO (a) is a
      unidimensional latent construct, (b) can be distinguished from and is not
      reducible to the 2 interacting individuals' qualities (responsiveness and
      positive affect), and (c) has remarkable measurement equivalence from ages 7 to
      15 months for both mother-child and father-child relationships and has remarkable
      measurement equivalence across both parent-child relationships at both child
      ages. This study represents an effort to advance the science of relationships by
      moving away from individual-based measures to dyadic measures and by using
      contemporary data analytic strategies.

PMID- 16953691
TI  - Differing profiles of developmental experiences across types of organized youth
      activities.
AB  - This study inventoried the types of developmental and negative experiences that
      youth encounter in different categories of extracurricular and community-based
      organized activities. A representative sample of 2,280 11th graders from 19
      diverse high schools responded to a computer-administered protocol. Youth in
      faith-based activities reported higher rates of experiences related to identity,
      emotional regulation, and interpersonal development in comparison with other
      activities. Sports and arts programs stood out as providing more experiences
      related to development of initiative, although sports were also related to high
      stress. Service activities were associated with experiences related to
      development of teamwork, positive relationships, and social capital. Youth
      reported all of these positive developmental experiences to occur significantly
      more often in youth programs than during school classes.

PMID- 16953692
TI  - Leaving home or still in the nest? Parent-child relationships and psychological
      health as predictors of different leaving home patterns.
AB  - In this study, the author examines the patterns of leaving home in a sample of 93
      participants and their parents. The quality of parent-child relationships,
      psychological symptomatology in adolescence and young adulthood, and attachment
      representation were assessed longitudinally from mid-adolescence to young
      adulthood. Attachment representation, adolescent autonomy, and parent-adolescent
      conflict were found to be important predictors of the timing of leaving home. In
      time leavers were more securely attached and had been granted high autonomy
      during adolescence, compared with participants who had left home later or had
      returned to reside in the family home. Young adults with nonnormative leaving
      home patterns also showed higher percentages of insecure attachment
      representations and lower percentages of involvement with a romantic partner.
      Participants residing with their parents were, according to their parents'
      perceptions, less psychologically healthy.

PMID- 16953693
TI  - Reactive personality-environment transactions and adult developmental
      trajectories.
AB  - The possibility, which is based on the concept of reactive personality
      environment transactions, that individuals learn different things from the same
      experience as a function of personality differences may help explain individual
      differences in adult developmental trajectories. In an analogue, longitudinal
      design, business students were taught about stock market investing, and they
      engaged in 5 practice investment sessions. Although all participants earned the
      same returns on their investments, they varied in the expectancies they formed
      about stock investing as a function of their personality status. As anticipated,
      behavioral inhibition (heightened sensitivity to punishment) facilitated
      formation of negative investing expectancies and antagonized formation of
      positive investing expectancies, and behavioral activation (heightened
      sensitivity to reward) facilitated formation of positive investing expectancies
      and antagonized formation of negative investing expectancies. Differential
      learning in a task that approximated skill acquisition for a developmental
      transition implies that personality may help shape individual developmental
      trajectories in the adult years.

PMID- 16953694
TI  - Prospective predictors of body dissatisfaction in adolescent girls and boys: a
      five-year longitudinal study.
AB  - This study investigated prospective risk factors for increases in body
      dissatisfaction in adolescent girls and boys in the Eating Among Teens Project.
      At the time of first assessment (Time 1), participants were a cohort of early
      adolescent girls (N=440) and boys (N=366) and a cohort of middle adolescent girls
      (N=946) and boys (N=764). Participants were followed up 5 years later (Time 2).
      Potential prospective risk factors examined included body mass index,
      socioeconomic status, ethnicity, parent dieting environment, peer environment,
      and psychological factors. Predictors of Time 2 body dissatisfaction were Time 1
      body dissatisfaction, body mass index, socioeconomic status, being African
      American, friend dieting and teasing, self-esteem, and depression. However, the
      profile of predictors differed across the samples.

PMID- 16953695
TI  - Make the first move: how infants learn about self-propelled objects.
AB  - In 3 experiments, the author investigated 16- to 20-month-old infants' attention
      to dynamic and static parts in learning about self-propelled objects. In
      Experiment 1, infants were habituated to simple noncausal events in which a
      geometric figure with a single moving part started to move without physical
      contact from an identical geometric figure that possessed a single static part.
      Infants were then tested with an event in which the parts of the objects were
      switched. In Experiments 2 and 3, infants were habituated and tested with
      identical events except that the part possessed by each object during habitation
      was switched relative to the first experiment. Results of the experiments
      revealed that 16-month-olds failed to encode the relation between an object's
      part and its onset of motion, 18-month-olds were unconstrained in the relations
      involving self-propulsion that they would encode, and 20-month-olds were
      constrained in the relations they would encode. The results are discussed with
      regard to the developmental trajectory of learning about motion properties and
      the mechanism involved in early concept acquisition.

PMID- 16953696
TI  - Profiles of externalizing behavior problems for boys and girls across preschool:
      the roles of emotion regulation and inattention.
AB  - Although externalizing behavior typically peaks in toddlerhood and decreases by
      school entry, some children do not show this normative decline. A sample of 383
      boys and girls was assessed at ages 2, 4, and 5 for externalizing behavior and at
      age 2 on measures of emotion regulation and inattention. A longitudinal latent
      profile analysis was performed and resulted in 4 longitudinal profiles of
      externalizing behavior for each gender. Poor emotion regulation and inattention
      were important predictors of membership in the chronic-clinical profile for
      girls, whereas socioeconomic status and inattention were important predictors of
      membership in the chronic-clinical profile for boys. Results are discussed with
      respect to the development of adaptive skills that lead to normative declines in
      externalizing behavior across childhood.

PMID- 16953697
TI  - The contribution of peer and media influences to the development of body
      satisfaction and self-esteem in young girls: a prospective study.
AB  - This study aimed to prospectively examine the role of peer and media influences
      in the development of body satisfaction (incorporating the desire for thinness
      and satisfaction with appearance) in young girls, as well as the relationship
      between body satisfaction and self-esteem. A sample of 97 girls 5-8 years of age
      completed individual interviews at Time 1 and 1 year later at Time 2. Linear
      panel analyses found that Time 1 perception of peers' desire for thinness was
      temporally antecedent to girls' desire for thinness, appearance satisfaction, and
      self-esteem 1 year later. In addition, the watching of appearance-focused
      television programs was temporally antecedent to appearance satisfaction.
      Finally, girls' desire for thinness was found to temporally precede low self
      esteem. Thus, as early as school entry, girls appear to already live in a culture
      in which peers and the media transmit the thin ideal in a way that negatively
      influences the development of body image and self-esteem.

PMID- 16953698
TI  - Middle childhood and adolescent contextual and personal predictors of adult
      educational and occupational outcomes: a mediational model in two countries.
AB  - The authors examined the prediction of occupational attainment by age 40 from
      contextual and personal variables assessed during childhood and adolescence in 2
      participant samples: (a) the Columbia County Longitudinal Study, a study of 856
      third graders in a semirural county in New York State that began in 1960, and (b)
      the Jyvaskyla Longitudinal Study of Personality and Social Development, a study
      of 369 eight-year-olds in Jyvaskyla, Finland, that began in 1968. Both samples
      were followed up during adolescence and early and middle adulthood. Structural
      modeling analyses revealed that in both countries, for both genders, children's
      age 8 cognitive-academic functioning and their parents' occupational status had
      independent positive long-term effects on the children's adult occupational
      attainment, even after other childhood and adolescent personal variables were
      controlled for. Further, childhood and adolescent aggressive behavior negatively
      affected educational status in early adulthood, which in turn predicted lower
      occupational status in middle adulthood.

PMID- 16953699
TI  - Effects of mothers' perceptions of children's competence: the moderating role of
      mothers' theories of competence.
AB  - There is much evidence that parents' perceptions of children's competence affect
      the development of children's academic functioning. In the current research, the
      possibility that this is moderated by parents' theories about the stability of
      competence was examined. In a 2-wave, 1-year study of 126 children (9 to 12 years
      old) and their mothers, children's academic functioning (i.e., grades,
      perceptions of competence, attributions for performance, and mastery orientation)
      and affective functioning (i.e., self-esteem and depressive symptoms) were
      examined. Among mothers with relatively high entity theories, their perceptions
      acted as self-fulfilling prophecies foreshadowing children's academic and
      affective functioning over time. However, among mothers with relatively low
      entity theories, mothers' perceptions did not predict children's academic and
      affective functioning.

PMID- 16953700
TI  - Development of the false-memory illusion.
AB  - The counterintuitive developmental trend in the Deese-Roediger-McDermott (DRM)
      illusion (that false-memory responses increase with age) was investigated in
      learning-disabled and nondisabled children from the 6- to 14-year-old age range.
      Fuzzy-trace theory predicts that because there are qualitative differences in how
      younger versus older children and disabled versus nondisabled children connect
      meaning information across the words on DRM lists, certain key effects that are
      observed in adult studies will be absent in young children and in learning
      disabled children. Data on 6 such adult effects (list strength, recall inflation,
      delayed inflation, delayed stability, thematic intrusion, and true-false
      dissociation) were used to investigate this hypothesis, and the resulting data
      were consistent with prediction.

PMID- 16953701
TI  - Confidence intervals and replication: where will the next mean fall?
AB  - Confidence intervals (CIs) give information about replication, but many
      researchers have misconceptions about this information. One problem is that the
      percentage of future replication means captured by a particular CI varies
      markedly, depending on where in relation to the population mean that CI falls.
      The authors investigated the distribution of this percentage for varsigma known
      and unknown, for various sample sizes, and for robust CIs. The distribution has
      strong negative skew: Most 95% CIs will capture around 90% or more of replication
      means, but some will capture a much lower proportion. On average, a 95% CI will
      include just 83.4% of future replication means. The authors present figures
      designed to assist understanding of what CIs say about replication, and they also
      extend the discussion to explain how p values give information about replication.

PMID- 16953702
TI  - Information-theoretic latent distribution modeling: distinguishing discrete and
      continuous latent variable models.
AB  - Distinguishing between discrete and continuous latent variable distributions has
      become increasingly important in numerous domains of behavioral science. Here,
      the authors explore an information-theoretic approach to latent distribution
      modeling, in which the ability of latent distribution models to represent
      statistical information in observed data is emphasized. The authors conclude that
      loss of statistical information with a decrease in the number of latent values
      provides an attractive basis for comparing discrete and continuous latent
      variable models. Theoretical considerations as well as the results of 2 Monte
      Carlo simulations indicate that information theory provides a sound basis for
      modeling latent distributions and distinguishing between discrete and continuous
      latent variable models in particular.

PMID- 16953703
TI  - On the power of multivariate latent growth curve models to detect correlated
      change.
AB  - We evaluated the statistical power of single-indicator latent growth curve models
      (LGCMs) to detect correlated change between two variables (covariance of slopes)
      as a function of sample size, number of longitudinal measurement occasions, and
      reliability (measurement error variance). Power approximations following the
      method of Satorra and Saris (1985) were used to evaluate the power to detect
      slope covariances. Even with large samples (N = 500) and several longitudinal
      occasions (4 or 5), statistical power to detect covariance of slopes was moderate
      to low unless growth curve reliability at study onset was above .90. Studies
      using LGCMs may fail to detect slope correlations because of low power rather
      than a lack of relationship of change between variables. The present findings
      allow researchers to make more informed design decisions when planning a
      longitudinal study and aid in interpreting LGCM results regarding correlated
      interindividual differences in rates of development.

PMID- 16953704
TI  - Ramsay-curve item response theory (RC-IRT) to detect and correct for nonnormal
      latent variables.
AB  - Popular methods for fitting unidimensional item response theory (IRT) models to
      data assume that the latent variable is normally distributed in the population of
      respondents, but this can be unreasonable for some variables. Ramsay-curve IRT
      (RC-IRT) was developed to detect and correct for this nonnormality. The primary
      aims of this article are to introduce RC-IRT less technically than it has been
      described elsewhere; to evaluate RC-IRT for ordinal data via simulation,
      including new approaches for model selection; and to illustrate RC-IRT with
      empirical examples. The empirical examples demonstrate the utility of RC-IRT for
      real data, and the simulation study indicates that when the latent distribution
      is skewed, RC-IRT results can be more accurate than those based on the normal
      model. Along with a plot of candidate curves, the Hannan-Quinn criterion is
      recommended for model selection.

PMID- 16953705
TI  - Clustering, seriation, and subset extraction of confusion data.
AB  - The study of confusion data is a well established practice in psychology.
      Although many types of analytical approaches for confusion data are available,
      among the most common methods are the extraction of 1 or more subsets of stimuli,
      the partitioning of the complete stimulus set into distinct groups, and the
      ordering of the stimulus set. Although standard commercial software packages can
      sometimes facilitate these types of analyses, they are not guaranteed to produce
      optimal solutions. The authors present a MATLAB *.m file for preprocessing
      confusion matrices, which includes fitting of the similarity-choice model. Two
      additional MATLAB programs are available for optimally clustering stimuli on the
      basis of confusion data. The authors also developed programs for optimally
      ordering stimuli and extracting subsets of stimuli using information from
      confusion matrices. Together, these programs provide several pragmatic
      alternatives for the applied researcher when analyzing confusion data. Although
      the programs are described within the context of confusion data, they are also
      amenable to other types of proximity data.

PMID- 16953706
TI  - Measurement of psychological disorders using cognitive diagnosis models.
AB  - Cognitive diagnosis models are constrained (multiple classification) latent class
      models that characterize the relationship of questionnaire responses to a set of
      dichotomous latent variables. Having emanated from educational measurement,
      several aspects of such models seem well suited to use in psychological
      assessment and diagnosis. This article presents the development of a new
      cognitive diagnosis model for use in psychological assessment--the DINO
      (deterministic input; noisy "or" gate) model--which, as an illustrative example,
      is applied to evaluate and diagnose pathological gamblers. As part of this
      example, a demonstration of the estimates obtained by cognitive diagnosis models
      is provided. Such estimates include the probability an individual meets each of a
      set of dichotomous Diagnostic and Statistical Manual of Mental Disorders (text
      revision [DSM-IV-TR]; American Psychiatric Association, 2000) criteria, resulting
      in an estimate of the probability an individual meets the DSM-IV-TR definition
      for being a pathological gambler. Furthermore, a demonstration of how the
      hypothesized underlying factors contributing to pathological gambling can be
      measured with the DINO model is presented, through use of a covariance structure
      model for the tetrachoric correlation matrix of the dichotomous latent variables
      representing DSM-IV-TR criteria.

PMID- 16953707
TI  - Meta-analysis of coefficient alpha.
AB  - The meta-analysis of coefficient alpha across many studies is becoming more
      common in psychology by a methodology labeled reliability generalization.
      Existing reliability generalization studies have not used the sampling
      distribution of coefficient alpha for precision weighting and other common meta
      analytic procedures. A framework is provided for a statistically grounded meta
      analysis of coefficient alpha using its sampling distribution. Two empirical
      examples are offered to illustrate these methods, and limitations of reliability
      generalization are described.

PMID- 16953708
TI  - Visual word recognition without central attention: evidence for greater
      automaticity with advancing age.
AB  - The present experiments examined the automaticity of word recognition. The
      authors examined whether people can recognize words while central attention is
      devoted to another task and how this ability changes across the life span. In
      Experiment 1, a lexical decision Task 2 was combined with either an auditory or a
      visual Task 1. Regardless of the Task 1 modality, Task 2 word recognition
      proceeded in parallel with Task 1 central operations for older adults but not for
      younger adults. This is a rare example of improved cognitive processing with
      advancing age. When Task 2 was nonlexical (Experiment 2), however, there was no
      evidence for greater parallel processing for older adults. Thus, the processing
      advantage appears to be restricted to lexical processes. The authors conclude
      that greater cumulative experience with lexical processing leads to greater
      automaticity, allowing older adults to more efficiently perform this stage in
      parallel with another task.

PMID- 16953709
TI  - The effect of word frequency, word predictability, and font difficulty on the eye
      movements of young and older readers.
AB  - Young adult and older readers' eye movements were recorded as they read sentences
      containing target words that varied in frequency or predictability. In addition,
      half of the sentences were printed in a font that was easy to read (Times New
      Roman) and the other half were printed in a font that was more difficult to read
      (Old English). Word frequency, word predictability, and font difficulty effects
      were apparent in the eye movement data of both groups of readers. In the fixation
      time data, the pattern of results was the same, but the older readers had larger
      frequency and predictability effects than the younger readers. The older readers
      skipped words more often than the younger readers (as indicated by their skipping
      rate on selected target words), but they made more regressions back to the target
      words and more regressions overall. The E-Z Reader model was used as a platform
      to evaluate the results, and simulations using the model suggest that lexical
      processing is slowed in older readers and that, possibly as a result of this,
      they adopt a more risky reading strategy.

PMID- 16953710
TI  - Event understanding and memory in healthy aging and dementia of the Alzheimer
      type.
AB  - Segmenting ongoing activity into events is important for later memory of those
      activities. In the experiments reported in this article, older adults'
      segmentation of activity into events was less consistent with group norms than
      younger adults' segmentation, particularly for older adults diagnosed with mild
      dementia of the Alzheimer type. Among older adults, poor agreement with others'
      event segmentation was associated with deficits in recognition memory for
      pictures taken from the activity and memory for the temporal order of events.
      Impaired semantic knowledge about events also was associated with memory
      deficits. The data suggest that semantic knowledge about events guides encoding,
      facilitating later memory. To the extent that such knowledge or the ability to
      use it is impaired in aging and dementia, memory suffers.

PMID- 16953711
TI  - The associative-memory basis of cognitive skill learning: adult age differences.
AB  - It has been established that memorizing common problems and their solutions
      underlies cognitive skill development, and that there are substantial age
      deficits in the rate of this learning. In a between-groups design, the authors
      compared learning rates for the same set of problems in skill (SK) training and
      paired-associate (PA) training. The authors found main effects due to condition
      (PA problems were acquired earlier) and to age (older adults' learning was
      delayed), but no condition-by-age interaction. The authors concluded that the age
      deficit in SK can be accounted for by the age deficit in associative memory; no
      further explanation is needed. The authors also analyzed fast and slow retrieves
      in SK and PA, and found that the frequency of fast retrieves did not differ in
      the two conditions. The overall advantage of PA was due to the occurrence of slow
      retrieves, which were absent in SK presumably because the skill algorithm
      displaces slow, explicit memory search in SK, but not fast, familiarity-based
      retrieval.

PMID- 16953712
TI  - Effects of environmental support and strategy training on older adults' use of
      context.
AB  - Age-related cognitive differences may be due, in part, to difficulties using task
      relevant context in a proactive manner. Two studies evaluated different methods
      for increasing older adults' use of context in the AX-Continuous Performance Task
      (H. E. Rosvold, A. F. Mirsky, I. Sarason, E. D. Bransome, & L. H. Beck, 1956),
      which evaluates components of context processing. The results suggest that (a)
      age differences in the use of context are not due to reduced access to cue
      information, (b) directed strategy training made older adults' context processing
      performance more like that of young adults, and (c) similar performance changes
      could be observed with less directed instruction and extended practice. These
      results suggest that age-related differences in context processing can be
      ameliorated by directed strategy training or extended practice.

PMID- 16953713
TI  - Autobiographical memory, autonoetic consciousness, and self-perspective in aging.
AB  - In this study, the authors examined the effects of aging on autobiographical
      memory in 180 participants by means of a new method designed to assess across 5
      lifetime periods the nature of memories-that is, specificity and spontaneity--and
      the phenomenal experience of remembering--that is, self-perspective and
      autonoetic consciousness--via the field/observer and remember/know paradigms
      respectively. Age-related differences were found for the specificity and
      spontaneity of memories and the phenomenal experience of remembering. There was
      an increase in observer and know responses with age, but a decrease in field and
      remember responses and in the ability to justify them by recalling sensory
      perceptive, affective, or spatiotemporal specific details. This pattern confirms
      the existence of a semantic-episodic dissociation in autobiographical memory in
      aging. Moreover, the data support the view that older participants can
      subjectively "travel back in time" to relive personal events in the most distant
      past better than those in the recent past.

PMID- 16953714
TI  - Age-related deficits in guided search using cues.
AB  - The ability of young and older adults to engage in guided conjunction search was
      tested in 2 experiments. In the cued condition, a picture of the target was
      presented before the search. In the noncued condition, there was no picture of
      the target. In Experiment 1, the cue was presented for 200 ms; the magnitude of
      the cuing effect (noncued response time--cued response time) was greater for the
      young than for the older observers. In Experiment 2 (older observers only), the
      cue duration was doubled, and older observers had a larger magnitude of cuing
      effect than found in Experiment 1 but not as large as what would be expected
      under generalized slowing. The results indicated that older observers had
      difficulty with interpreting the cue and setting search parameters when the
      target varied across trials.

PMID- 16953715
TI  - Stress-related cognitive interference predicts cognitive function in old age.
AB  - Both subjective distress and cognitive interference have been proposed as
      mechanisms underlying the negative effects of stress on cognition. Studies of
      aging have shown that distress is associated with lower cognitive performance,
      but none have examined the effects of cognitive interference. One hundred eleven
      older adults (M-sub(age)=80) completed measures of working memory, processing
      speed, and episodic memory as well as self-report measures of subjective distress
      and cognitive interference. Cognitive interference was strongly associated with
      poorer performance on all 3 cognitive constructs, whereas distress was only
      modestly associated with lower working memory. The results suggest that cognitive
      process related to stress is an important predictor of cognitive function in
      advanced age.

PMID- 16953716
TI  - Intraindividual coupling of daily stress and cognition.
AB  - Most psychological theories predict associations among processes that transpire
      within individuals. However, these theories are often tested by examining
      relationships at the between-persons (BP) rather than the within-persons (WP)
      level. The authors examined the WP and BP relationships between daily stress and
      daily variability in cognitive performance. Daily stress and cognitive
      performance were assessed on 6 occasions in 108 older adults and 68 young adults.
      WP variability in stress predicted WP variability in response times (RTs) on a 2
      back working memory task in both younger and older adults. That is, RTs were
      slower on high-stress days compared with low-stress days. There was evidence of
      an amplified WP stress effect in the older adults on a serial attention task.
      There was no evidence of stress effects on simple versions of these tasks that
      placed minimal demands on working memory. These results are consistent with
      theories that postulate that stress-related cognitive interference competes for
      attentional resources.

PMID- 16953717
TI  - Age effects on social cognition: faces tell a different story.
AB  - The authors administered social cognition tasks to younger and older adults to
      investigate age-related differences in social and emotional processing. Although
      slower, older adults were as accurate as younger adults in identifying the
      emotional valence (i.e., positive, negative, or neutral) of facial expressions.
      However, the age difference in reaction time was largest for negative faces.
      Older adults were significantly less accurate at identifying specific facial
      expressions of fear and sadness. No age differences specific to social function
      were found on tasks of self-reference, identifying emotional words, or theory of
      mind. Performance on the social tasks in older adults was independent of
      performance on general cognitive tasks (e.g., working memory) but was related to
      personality traits and emotional awareness. Older adults also showed more
      intercorrelations among the social tasks than did the younger adults. These
      findings suggest that age differences in social cognition are limited to the
      processing of facial emotion. Nevertheless, with age there appears to be
      increasing reliance on a common resource to perform social tasks, but one that is
      not shared with other cognitive domains.

PMID- 16953718
TI  - Personality and risk of cognitive impairment 25 years later.
AB  - The authors examined the relationship between personality and cognitive
      impairment in 4,039 members of the Swedish Twin Registry. Neuroticism and
      extraversion scores were collected in 1973 at midlife, and cognitive impairment
      was assessed in the same group 25 years later. Data were analyzed with case
      control and co-twin control designs. Greater neuroticism was associated with
      higher risk of cognitive impairment in the results from case-control, but not
      from co-twin, analyses. Compared with both extraversion and introversion,
      moderate extraversion was associated with lower risk of cognitive impairment in
      both case-control and co-twin designs, as was the combination of high neuroticism
      and low extraversion. Findings are discussed in the context of theories related
      to personality, psychological distress, arousal, and cognitive function.

PMID- 16953719
TI  - Age differences in attitude change: influences of cognitive resources and
      motivation on responses to argument quantity.
AB  - This study examined the influences of cognitive resources and motivation on how
      young and older adults process different quantities of persuasive arguments. In
      the first experiment session, both young and older adults rated their attitudes
      toward marijuana legalization and capital punishment. After a week, they read
      either 3 or 9 similar-quality arguments supporting marijuana legalization and
      capital punishment. Half of participants were assigned to the high-involvement
      condition (i.e., told that they were going to discuss the arguments later with
      the experimenter) and the other half were assigned to the low-involvement
      condition (i.e., given no instructions). After reading the arguments,
      participants rated their attitudes toward those 2 social issues again. Highly
      involved young adults changed their attitudes regardless of the quantity of
      arguments, whereas lowly involved young adults' attitude change was influenced by
      the argument quantity. Older adults in both high-involvement and low-involvement
      conditions changed their attitudes according to the argument quantity. Working
      memory was found to mediate the age effects on attitude change. This finding
      demonstrated the importance of a cognitive mechanism in accounting for age
      differences in attitude change.

PMID- 16953720
TI  - Social support as a predictor of variability: an examination of the adjustment
      trajectories of recent widows.
AB  - The variability pattern of emotional well-being in recent widows across a 98-day
      period beginning in the first month post-loss has previously been modeled by
      dynamical systems and shown to be an oscillating process that damps across time.
      The goal of the present study was to examine how variables that comprise the
      social support network predict characteristics of these emotional shifts in 28
      recent widows. In the present study, emotional support seeking led to a steeper
      overall trend, whereas perceived control for social support led to a shallower
      overall trend. When examining intraindividual variability, instrumental support
      seeking predicted a slower damping rate. Understanding the individual differences
      in the variability patterns of recent widows is a necessary step in identifying
      the etiology of adjustment to widowhood.

PMID- 16953721
TI  - Marital closeness, functional disability, and adjustment in late life.
AB  - Socioemotional selectivity theory (SST) posits that emotionally close
      relationships are increasingly valued as people perceive constraints on time.
      Based on SST, this study of 1,532 older married persons hypothesized that
      emotional dimensions of marriage would more strongly predict adjustment at higher
      levels of functional disability. High levels of marital closeness were negatively
      associated with depression and anxiety and positively associated with self
      esteem. Consistent with predictions derived from SST, marital closeness moderated
      the negative psychological effects of high levels of functional disability on
      depression, anxiety, and self-esteem. Results are discussed in the context of SST
      and traditional stress-buffering models of social support.

PMID- 16953722
TI  - Does marriage protect older people from distress? The role of equity and recency
      of bereavement.
AB  - The association between marital status and distress was examined in a largely
      neglected group, namely older people (65 and older; N = 1,649). In this 2-wave
      study, married persons were less distressed than single persons, but perceived
      equity within the marriage and recency of bereavement qualified these findings.
      Married persons who felt inequitably treated were more distressed than persons
      who had always been single. Married persons reported less distress than recently
      (= 2 years ago) widowed persons, but only equitably treated married persons
      reported less distress than persons widowed for more than 2 years. Increased
      distress between the 2 waves occurred in recently widowed persons, and there was
      a decrease in distress in persons who were widowed shortly before the 1st wave.
      No gender effects were found.

PMID- 16953723
TI  - Age-related variation in the influences of aging stereotypes on memory in
      adulthood.
AB  - Adults 24-86 years of age read positive or negative information about aging and
      memory prior to a memory test. The impact of this information on recall
      performance varied with age. Performance in the youngest and oldest participants
      was minimally affected by stereotype activation. Adults in their 60s exhibited
      weak effects consistent with the operation of stereotype threat, whereas middle
      age adults exhibited a contrast effect in memory performance, suggestive of
      stereotype lift. Beliefs about aging and memory were also affected by stereotypic
      information, and older adults' changed beliefs were more important in predicting
      performance than was exposure to stereotype-based information alone.

PMID- 16953724
TI  - Marital discord and well-being in older adults: is the association confounded by
      personality?
AB  - The associations between marital discord and multiple measures of well-being
      (depression, anxiety, life satisfaction, and self-esteem) were evaluated in a
      population-based sample of 416 couples in which the husband was 65 years or
      older. Results indicated that greater marital discord was associated with greater
      depression and lower life satisfaction and self-esteem. Furthermore, the
      associations between marital discord and well-being remained significant when
      statistically controlling for the rival explanation of the Big Five personality
      traits. Finally, there was little evidence for gender differences in the
      magnitude of the associations between marital discord and well-being. Findings
      suggest that marital discord is an important correlate of multiple measures of
      well-being in older individuals and that this association is not confounded by
      the Big Five personality traits.

PMID- 16953725
TI  - Short-term visual recognition and temporal order memory are both well-preserved
      in aging.
AB  - Increased difficulty with memory for recent events is a well-documented
      consequence of normal aging, but not all aspects of memory are equally affected.
      To compare the impact of aging on short-term recognition and temporal order
      memory, young and older adults were asked to identify the serial position that a
      probe item had occupied in a study set, or to judge that the probe was novel (had
      not been in the study set). Stimuli were compound sinusoidal gratings, which
      resist verbal description and rehearsal. With retention intervals of 1 or 4
      seconds, young and older adults produced highly similar overall performance,
      serial position curves, and proportions of trials on which a correct recognition
      response was accompanied by an incorrect temporal order judgment. Temporal order
      errors, which occurred on about one quarter of trials, were traced to two
      factors: perceptual similarity between the wrongly identified study item and the
      correct item, and temporal similarity between the wrongly identified item and the
      correct one. Our results show that short-term visual temporal order memory is
      well-preserved in normal aging, and when temporal order errors do occur, they
      arise from similar causes for young and older people.

PMID- 16953726
TI  - Age deficits in the control of prepotent responses: evidence for an inhibitory
      decline.
AB  - Older adults have more difficulty than younger adults appropriately directing
      their behavior when the required response is in competition with a prepotent
      response. The authors varied the difficulty of inhibiting a prepotent eye
      movement response by varying the response cue (peripheral onset or central
      arrow). The response cue manipulation did not affect prosaccade accuracy and
      latency for either age group and did not affect younger adults' antisaccades.
      Older adults' antisaccades were slower in the peripheral cue condition than in
      the central arrow condition. These findings are taken as support for the
      inhibitory deficit hypothesis of aging (L. Hasher, R. T. Zacks, & C. P. May,
      1999).

PMID- 16953727
TI  - A formal cognitive model of the go/no-go discrimination task: evaluation and
      implications.
AB  - This article proposes and tests a formal cognitive model for the go/no-go
      discrimination task. In this task, the performer chooses whether to respond to
      stimuli and receives rewards for responding to certain stimuli and punishments
      for responding to others. Three cognitive models were evaluated on the basis of
      data from a longitudinal study involving 400 adolescents. The results show that a
      cue-dependent model presupposing that participants can differentiate between cues
      was the most accurate and parsimonious. This model has 3 parameters denoting the
      relative impact of rewards and punishments on evaluations, the rate that
      contingent payoffs are learned, and the consistency between learning and
      responding. Commission errors were associated with increased attention to
      rewards; omission errors were associated with increased attention to punishments.
      Both error types were associated with low choice consistency. The parameters were
      also shown to have external validity: Attention to rewards was associated with
      externalizing behavior problems on the Achenbach scale, and choice consistency
      was associated with low Welsh anxiety. The present model can thus potentially
      improve the sensitivity of the task to differences between clinical populations.

PMID- 16953728
TI  - Evaluating the latent structure of the MMPI-2 F(p) scale in a forensic sample: a
      taxometric analysis.
AB  - P. A. Arbisi and Y. S. Ben-Porath (1995) originally proposed that the Infrequency
      Psychopathology scale, F(p), be used as the final step in an algorithm to
      determine the validity of a Minnesota Multiphasic Personality Inventory-2 (MMPI
      2) protocol. The current study used taxometric procedures to determine the latent
      structure of F(p) among examinees with profiles that would necessitate the
      interpretation of F(p) when using Arbisi and Ben-Porath's proposed algorithm.
      Participants included a subsample of 289 consecutively referred pretrial forensic
      examinees adjudicated incompetent to stand trial with high Infrequency (F) scale
      scores, thereby providing a sample that would be expected to have a high base
      rate of persons with bona fide psychopathology and persons with incentive to
      overreport psychopathology. Using MAMBAC and MAXEIG, F(p) produced a taxonic
      latent structure within the subgroup of examinees who obtained raw scores on F of
      greater than 17. These results support Arbisi and Ben-Porath's original proposal
      to use F(p) to identify a distinct subgroup of overreported MMPI-2 protocols
      within forensic psychiatric examinees with high elevations on F. Implications and
      suggestions for future research are provided.

PMID- 16953729
TI  - Psychometric qualities of the German version of the Posttraumatic Diagnostic
      Scale (PTDS).
AB  - In the present study, the psychometric properties of the German version of the
      Posttraumatic Diagnostic Scale (PTDS; A. Ehlers, R. Steil, H. Winter, & E. B.
      Foa, 1996) were evaluated in a sample of 143 trauma survivors. To investigate
      convergent and discriminant validity of this questionnaire, the authors assessed
      posttraumatic stress disorder (PTSD), anxiety, depression symptoms, and social
      phobia. Internal consistencies of the PTDS and its subscales as well as their
      association with related measures show that the German PTDS is a reliable and
      valid instrument for the assessment of posttraumatic stress symptoms. A 3-factor
      structure was found that is, however, not exactly in concordance with the
      Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.;
      American Psychiatric Association, 2000) formulation (Reexperiencing, Avoidance,
      and Hyperarousal) but rather comprises a Reexperiencing/Avoidance factor; an
      Emotional Numbing/Hyperarousal factor; and a 3rd factor, consisting of
      Hypervigilance and an Exaggerated Startle Response. The findings are discussed
      with respect to their equivalency to the original PTDS, core symptoms of PTSD,
      and desirable future research.

PMID- 16953730
TI  - The Social Phobia Inventory: validity and reliability in an adolescent community
      sample.
AB  - Social anxiety disorder and social anxiety are highly prevalent psychological
      conditions in youth. Because of the known risks associated with the spectrum of
      social anxiety in youth, early detection with valid and reliable assessment
      measures is imperative. Self-report measures have become the most widely used
      method of assessment for child and adolescent social anxiety. Because research to
      date on self-report measures of social anxiety disorder in adolescents is
      limited, the primary objective of the present study was to contribute to the
      literature by examining the validity and reliability of a new self-report
      measure, the Social Phobia Inventory (SPIN), in a community sample of
      adolescents. The SPIN is a 17-item measure purported to assess the full spectrum
      of social anxiety disorder symptomatology. Previously, psychometric research on
      the SPIN in adult populations has demonstrated its validity and reliability. In
      the current psychometric examination, results revealed strong support for the
      temporal stability, internal consistency, and construct validity of the SPIN,
      suggesting it is an appropriate screening measure for the assessment of social
      anxiety disorder in adolescents.

PMID- 16953731
TI  - Factor structure of coping: two studies of mothers with high levels of life
      stress.
AB  - Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were
      used to investigate the factor structure of coping in mothers with high levels of
      life stress. In Study 1, EFA of the Coping Orientation to Problems Experienced
      (C. S. Carver, M. F. Scheier, & J. K. Weintraub, 1989) in a sample of mothers of
      full-term or very low birth weight 2-year-old children yielded 7 reliable coping
      factors. Each factor accounted for significant variance in at least 1 of 6
      outcomes measuring maternal-child well-being. In Study 2, CFA was used to cross
      validate the EFA model on the basis of the responses of mothers of 2-year-old
      children with prenatal polysubstance exposure. CFA results revealed a moderately
      good fit, confirming the factor structure in a 2nd, independent sample of mothers
      with high levels of life stress.

PMID- 16953732
TI  - Acceptance in romantic relationships: the frequency and acceptability of partner
      behavior inventory.
AB  - Despite the recent emphasis on acceptance in romantic relationships, no validated
      measure of relationship acceptance presently exists. To fill this gap, the 20
      item Frequency and Acceptability of Partner Behavior Inventory (FAPBI; A.
      Christensen & N. S. Jacobson, 1997) was created to assess separately the
      acceptability and frequency of both positive and negative relationship behaviors.
      Data from 12,752 community individuals, 415 community couples, and 134 couples
      seeking marital therapy indicated that the FAPBI comprises four factors:
      Affection, Closeness, Demand, and Violation. These factors were consistent across
      gender, relationship type, and sexual orientation. Furthermore, the factors were
      internally consistent, correlated with relationship satisfaction, and
      differentiated couples seeking marital therapy from nondistressed couples in the
      community.

PMID- 16953733
TI  - Suicide Attempt Self-Injury Interview (SASII): development, reliability, and
      validity of a scale to assess suicide attempts and intentional self-injury.
AB  - The authors describe the development of the Suicide Attempt Self-Injury Interview
      (SASII), an instrument designed to assess the factors involved in nonfatal
      suicide attempts and intentional self-injury. Using 4 cohorts of participants,
      authors generated SASII items and evaluated them with factor and content analyses
      and internal consistency statistics. The final measure was assessed for
      reliability and validity with collateral measures. The SASII assesses variables
      related to method, lethality and impulsivity of the act, likelihood of rescue,
      suicide intent or ambivalence and other motivations, consequences, and habitual
      self-injury. The SASII was found to have very good interrater reliability and
      adequate validity.

PMID- 16953734
TI  - The equivalence of the Child Behavior Checklist/1 1/2-5 across parent
      race/ethnicity, income level, and language.
AB  - This study examined the equivalence of the Child Behavior Checklist/1 1/2-5
      (CBCL/1 1/2-5) in 682 parents of 2- to 4-year-old children stratified by parent
      race/ethnicity (African American, Latino, and non-Latino White), family income
      (low vs. middle-upper), and language version (Spanish vs. English). Externalizing
      Scale means differed by income and child gender. Internalizing Scale means
      differed by income and parent race/ethnicity. Differential item analyses showed
      that few items functioned differently by racial/ethnic, language, and income
      group. A confirmatory factor analysis demonstrated that the Externalizing Scale
      provided a good fit with the data across racial/ethnic and income groups.
      However, model fit was improved for the Internalizing Scale when factor weights
      were allowed to vary. Findings support the equivalence of the CBCL/1 1/2-5 when
      used with parents of low-income preschool children from African American and
      Latino backgrounds, although further study of the factor structure for the
      Internalizing Scale is recommended.

PMID- 16953735
TI  - Psychometric adequacy and comparability of the short and full forms of the
      Personality Assessment Inventory.
AB  - The 160-item short form of the Personality Assessment Inventory (PAI) was
      developed for situations in which respondents complete only the 1st half of the
      test. The present study evaluates the adequacy and comparability of the full and
      short forms of the PAI in terms of a wide range of psychometric characteristics.
      In all, 421 participants completed the full form as part of a neuropsychological
      evaluation. Results indicated slightly lower internal consistency reliability of
      the short compared with the full form. Group-level agreement of short and full
      form scales ranged from adequate to excellent. However, within-subject agreement
      was somewhat more variable. Low levels of within-subject agreement were strongly
      associated with elevated validity scale scores. The factor structures of the full
      and short forms showed high congruence for a 3-factor solution. These findings
      suggest that many scales of the short form have adequate comparability with their
      respective full form scales. However, low levels of reliability across less
      impaired ranges of the latent trait, diminished content coverage, and altered
      validity detection may limit the utility of some of the short form scales.

PMID- 16953736
TI  - Age-related invariance of abilities measured with the Wechsler Adult Intelligence
      Scale--III.
AB  - Examination of measurement invariance tests the assumption that the model
      underlying a set of test scores is directly comparable across groups. The
      observation of measurement invariance provides fundamental evidence for the
      inference that scores on a test afford equivalent measurement of the same
      psychological traits among diverse groups. Groups may be derived from different
      psychosocial backgrounds or different clinical presentations. In the Wechsler
      Adult Intelligence Scale-III (WAIS-III)/Wechsler Memory Scale-III (WMS-III)
      Technical Manual (Psychological Corporation, 2002), there appears to be a
      breakdown in factor structure among the standardization cases in older adults. In
      this study, the authors evaluated the invariance of the measurement model of the
      WAIS-III across 5 age bands. All components of the measurement model were
      examined. Overall, the evidence pointed to invariance across age of a modified 4
      factor model that included cross-loadings for the Similarities and Arithmetic
      subtests. These results support the utility of the WAIS-III as a measure of
      stable intelligence traits across a wide age range.

PMID- 16953737
TI  - The lay assessment of subclinical depression in daily life.
AB  - This study examined how laypersons assess subclinical depression in others on the
      basis of information about their daily lives. For 2 days, 96 participants were
      tracked with the Electronically Activated Recorder, a naturalistic observation
      method that samples ambient sounds from participants' momentary environments.
      Judges rated participants' levels of depression after listening to the sampled
      ambient sounds. Participants' depressive symptoms were assessed with the Beck
      Depression Inventory. Overall, judges showed little accuracy at determining
      participants' levels of depressive symptoms from the ambient sounds. Exploratory
      analyses, however, revealed that judges were more accurate among moderately and
      severely depressed participants, presumably because the cues judges used to
      assess depression (e.g., spending time alone, not socializing, not laughing)
      discriminated successfully only at high levels of subclinical depression.

PMID- 16953738
TI  - The reading grade level of common measures in child and adolescent clinical
      psychology.
AB  - The purpose of this article is to provide easily accessible readability
      information for 49 parent- and 35 child- and adolescent-report measures commonly
      used by clinicians and researchers. There is a great deal of variability in
      reading ability required across measures. The majority of parent-report measures
      (65%) required reading ability above the 8th grade level. The average child
      /adolescent-report measure required reading ability above the 6th grade level.
      Given the potential contribution of readability to a measure's reliability,
      validity, and overall utility, examining and accounting for readability should be
      a more common practice in test construction and administration.

PMID- 16953739
TI  - Confirmatory factor analysis of the Wechsler Intelligence Scale for Children-
      Third Edition in an Australian clinical sample.
AB  - A confirmatory factor analysis was conducted on the Wechsler Intelligence Scale
      for Children-Third Edition (WISC-III; D. Wechsler, 1991) with a sample of 579
      Australian children referred for assessment because of academic difficulties in
      the classroom. The children were administered the WISC-III as part of the initial
      eligibility determination process for funding of special education services. The
      children were aged between 6 years and 16 years 7 months. One-, two-, three-, and
      four-factor models were tested. The four-factor model proposed in the WISC-III
      manual fit the data significantly better than all other models tested.

PMID- 16953741
TI  - The impact of stress on mothers' memory of a natural disaster.
AB  - The effects of stress on mothers' recall for a major hurricane were studied.
      Stress was objectively defined as low, moderate, or high according to the
      severity of home damage. This study of 96 mothers was conducted concurrently with
      L. E. Bahrick, J. F. Parker, R. Fivush, and M. Levitt (1998), allowing the
      authors to compare child and adult recall as a function of the same stressor.
      There was a quadratic relationship between storm severity and total recall for
      adults, similar to their children. Mothers' recall increased from low to moderate
      severity, but recall at moderate severity did not differ from high severity.
      These findings help clarify the effects of stress on the amount and type of
      information adults recall in retrospective accounts of naturalistic, temporally
      extended events.

PMID- 16953740
TI  - Risk attitude in small timesaving decisions.
AB  - Four experiments are presented that explore situations in which a decision maker
      has to rely on personal experience in an attempt to minimize delays. Experiment 1
      shows that risk-attitude in these timesaving decisions is similar to risk
      attitude in money-related decisions from experience: A risky prospect is more
      attractive than a safer prospect with the same expected value only when it leads
      to a better outcome most of the time. Experiment 2 highlights a boundary
      condition: It suggests that a difficulty in ranking the relevant delays moves
      behavior toward random choice. Experiments 3 and 4 show that when actions must be
      taken during the delay (thereby helping compare delays), this increases the
      similarity of timesaving decisions to money-related decisions. In these settings
      the results reflect an increase in risk aversion with experience. The
      relationship of the results to the study of non-human time-related decisions,
      human money-related decisions and human time perception is discussed.

PMID- 16953742
TI  - Covariation neglect among novice investors.
AB  - In 4 experiments, undergraduates made hypothetical investment choices. In
      Experiment 1, participants paid more attention to the volatility of individual
      assets than to the volatility of aggregated portfolios. The results of Experiment
      2 show that most participants diversified even when this increased risk because
      of covariation between the returns of individual assets. In Experiment 3, nearly
      half of those who seemingly attempted to minimize risk diversified even when this
      increased risk. These results indicate that novice investors neglect covariation
      when diversifying across investment alternatives. Experiment 4 established that
      naive diversification follows from motivation to minimize risk and showed that
      covariation neglect was not significantly reduced by informing participants about
      how covariation affects portfolio risk but was reduced by making participants
      systematically calculate aggregate returns for diversified portfolios. In order
      to counteract naive diversification, novice investors need to be better informed
      about the rationale underlying recommendations to diversify.

PMID- 16953743
TI  - Olympic medals as fruits of comparison? Assimilation and contrast in sequential
      performance judgments.
AB  - The authors investigated the evaluative consequences of sequential performance
      judgments. Recent social comparison research has suggested that performance
      judgments may be influenced by judgments about a preceding performance.
      Specifically, performance judgments may be assimilated to judgments of the
      preceding performance if judges focus on similarities between the two. If judges
      focus on differences, however, contrast may ensue. The authors examined
      sequential performance judgments, using data gathered from the 2004 Olympic Games
      as well as data gathered in the laboratory with students or experienced
      gymnastics judges as participants. Sequential performance judgments were
      influenced by previously judged performances, and the direction of this influence
      depended on the degree of perceived similarity between the successive
      performances.

PMID- 16953744
TI  - Physician decision making and cardiac risk: effects of knowledge, risk
      perception, risk tolerance, and fuzzy processing.
AB  - Despite training, professionals sometimes make serious errors in risky decision
      making. The authors investigated judgments and decisions for 9 hypothetical
      patients at 3 levels of cardiac risk, comparing student and physician groups
      varying in domain-specific knowledge. Decisions were examined regarding whether
      they deviated from guidelines, how risk perceptions and risk tolerances
      determined decisions, and how the latter differed for knowledge groups. More
      knowledgeable professionals were better at discriminating levels of risk
      according to external correspondence criteria but committed similar errors in
      disjunctive probability judgments, violating internal coherence criteria. Also,
      higher knowledge groups relied on fewer dimensions of information than did lower
      knowledge groups. Consistent with fuzzy-trace theory, experts achieved better
      discrimination by processing less information and made sharper all-or-none
      distinctions among decision categories.

PMID- 16953745
TI  - A house divided? The psychology of red and blue America.
AB  - Recently it has become commonplace in America for commentators and the public to
      use the terms "red" and "blue" to refer to perceived cultural differences in
      America and American politics. Although a political divide may exist in America
      today, these particular terms are inaccurate and reductive. This article presents
      research from social psychology demonstrating that the increased use of these
      terms is likely to increase the conflict between political groups in America by
      making political conflict salient in nonpolitical contexts, reducing the ability
      of Americans to form multifaceted complex identities, pushing Americans to
      misperceive political in-groups and out-groups, and contributing to a "spiral of
      silence." An alternative model for discussing cultural differences is proposed.

PMID- 16953746
TI  - The virtue of multiculturalism: personal transformation, character, and openness
      to the other.
AB  - The social, intellectual, and moral movement known as multiculturalism has been
      enormously influential in psychology. Its ability to reshape psychology has been
      due to its ethical force, which derives from the attractiveness of its aims of
      inclusion, social justice, and mutual respect. The cultivation of cultural
      competence, presented as a developmental process of acquiring self-awareness,
      cultural knowledge, and skills, is an important emphasis in the multicultural
      literature. The authors place the cultural competence literature in dialogue with
      virtue ethics (a contemporary ethical theory derived from Aristotle) to develop a
      rich and illuminating way for psychologists to understand and embody the personal
      self-examination, commitment, and transformation required for learning and
      practicing in a culturally competent manner. According to virtue ethics,
      multiculturalism can be seen as the pursuit of worthwhile goals that require
      personal strengths or virtues, knowledge, consistent actions, proper motivation,
      and practical wisdom. The authors term the virtue of multiculturalism openness to
      the other and conclude by describing how attention to cultural matters also
      transforms virtue ethics in important and necessary ways.

PMID- 16953747
TI  - The complex relationship between dependency and domestic violence: converging
      psychological factors and social forces.
AB  - Research indicates that economic dependency in women and emotional dependency in
      men independently contribute to domestic-partner abuse risk and that high levels
      of emotional dependency in an abused partner may reduce the likelihood that the
      victimized person will terminate the relationship. An analysis of psychological
      factors and social forces that contribute to domestic violence suggests that
      multimodal intervention strategies are needed to combat this complex problem.

PMID- 16953748
TI  - Legal recognition of same-sex relationships in the United States: a social
      science perspective.
AB  - Whether and how civil society should recognize committed relationships between
      same-sex partners has become a prominent, often divisive, policy issue. The
      present article reviews relevant behavioral and social science research to assess
      the validity of key factual claims in this debate. The data indicate that same
      sex and heterosexual relationships do not differ in their essential psychosocial
      dimensions; that a parent's sexual orientation is unrelated to her or his ability
      to provide a healthy and nurturing family environment; and that marriage bestows
      substantial psychological, social, and health benefits. It is concluded that same
      sex couples and their children are likely to benefit in numerous ways from legal
      recognition of their families, and providing such recognition through marriage
      will bestow greater benefit than civil unions or domestic partnerships. Trends in
      public opinion toward greater support for legal recognition of same-sex couples
      are discussed.

PMID- 16953749
TI  - The evolution of personality variation in humans and other animals.
AB  - A comprehensive evolutionary framework for understanding the maintenance of
      heritable behavioral variation in humans is yet to be developed. Some
      evolutionary psychologists have argued that heritable variation will not be found
      in important, fitness-relevant characteristics because of the winnowing effect of
      natural selection. This article propounds the opposite view. Heritable variation
      is ubiquitous in all species, and there are a number of frameworks for
      understanding its persistence. The author argues that each of the Big Five
      dimensions of human personality can be seen as the result of a trade-off between
      different fitness costs and benefits. As there is no unconditionally optimal
      value of these trade-offs, it is to be expected that genetic diversity will be
      retained in the population.

PMID- 16953756
TI  - The importance of theory for evaluating evidence on sex differences.

PMID- 16953757
TI  - The gender reality hypothesis.

PMID- 16953758
TI  - An evolutionary psychological perspective on gender similarities and differences.

PMID- 16953760
TI  - Judgments of similarity are psychological: the importance of importance.

PMID- 16953761
TI  - An expanded perspective on children's mental health.

PMID- 16953763
TI  - Workplace aggression in teenage part-time employees.
AB  - Among adult employees, interpersonal injustice and abusive supervision predict
      aggression toward supervisors at work. The aim of this study was to assess
      whether similar relationships exist among teenage employees and, further, whether
      teenagers' reasons for working moderate these relationships. Multiple regression
      analyses on data from 119 teenage employees showed that financial and personal
      fulfillment reasons for working moderate the impact of interpersonal injustice
      and abusive supervision on aggression directed at workplace supervisors. These
      findings contribute to the understanding of workplace aggression by demonstrating
      that (a) teenagers engage in this workplace behavior, (b) the predictors are
      similar to those of adult aggression, and (c) reasons for working play a
      moderating role among this particular cohort. The possible long-term consequences
      of teenagers' use of aggression at work are discussed.

PMID- 16953764
TI  - Workplace harassment from the victim's perspective: a theoretical model and meta
      analysis.
AB  - Although workplace harassment affects the lives of many employees, until recently
      it has been relatively ignored in the organizational psychology literature.
      First, the authors introduced an attribution- and reciprocity-based model that
      explains the link between harassment and its potential causes and consequences.
      The authors then conducted a meta-analysis to examine the potential antecedents
      and consequences of workplace harassment. As shown by the meta-analysis, both
      environmental and individual difference factors potentially contributed to
      harassment and harassment was negatively related to the well-being of both
      individual employees and their employing organizations. Furthermore, harassment
      contributed to the variance in many outcomes, even after controlling for 2 of the
      most commonly studied occupational stressors, role ambiguity and role conflict.

PMID- 16953765
TI  - Understanding attitudes toward affirmative action programs in employment: summary
      and meta-analysis of 35 years of research.
AB  - Affirmative action programs (AAPs) are controversial employment policies in the
      United States and elsewhere. A large body of evidence about attitudinal reactions
      to AAPs in employment has accumulated over 35 years: at least 126 independent
      samples involving 29,000 people. However, findings are not firmly established or
      integrated. In the current article, the authors summarize and meta-analytically
      estimate relationships of AAP attitudes with (a) structural features of such
      programs, (b) perceiver demographic and psychological characteristics, (c)
      interactions of structural features with perceiver characteristics, and (d)
      presentation of AAP details to perceivers, including justification of the AAP.
      Results are generally consistent with predictions derived from self-interest
      considerations, organizational justice theory, and racism theories. They also
      suggest practical ways in which AAPs might be designed and communicated to
      employees to reduce attitudinal resistance.

PMID- 16953766
TI  - Stressing the group: social identity and the unfolding dynamics of responses to
      stress.
AB  - Participants in the British Broadcasting Corporation (BBC) prison study were
      randomly assigned to high-status (guard) and low-status (prisoner) groups.
      Structural interventions increased the prisoners' sense of shared group identity
      and their willingness to challenge the power of the guards. Psychometric,
      physiological, behavioral, and observational data support the hypothesis that
      identity-based processes also affected participants' experience of stress. As
      prisoners' sense of shared identity increased, they provided each other with more
      social support and effectively resisted the adverse effects of situational
      stressors. As guards' sense of shared identity declined, they provided each other
      with less support and succumbed to stressors. Findings support an integrated
      social identity model of stress that addresses intragroup and intergroup dynamics
      of the stress process.

PMID- 16953767
TI  - Episodic processes in emotional labor: perceptions of affective delivery and
      regulation strategies.
AB  - This study examined emotional labor processes from a within-person, episodic
      framework. The authors hypothesized that the influence of negative emotions on
      affective delivery would be lessened by regulation strategies for supervisor
      perceptions but not self-perceptions. In addition, difficulty maintaining display
      rules was hypothesized to mediate the relation between negative emotions and self
      perceptions of affective delivery. Finally, the influence of surface acting
      strategies on these processes as well as correlations with individual differences
      was investigated. Hypotheses were tested using ecological momentary assessment of
      a sample of cheerleading instructors. Results suggest that surface actors can
      regulate emotions effectively on an episode-to-episode basis but find the episode
      more difficult. In addition, surface actors exhibit more general tendencies to
      devalue themselves and experience fewer positive emotions.

PMID- 16953768
TI  - The moderating roles of self-esteem and neuroticism in the relationship between
      group and individual undermining behavior.
AB  - The authors developed and tested a multilevel interactive model of the
      relationship between group undermining and individual undermining behavior in 2
      multiwave studies of group members. Integrating the literature on group
      influences on individual behavior with the individual difference literature, the
      authors predicted a 3-way Group Undermining x Self-Esteem x Neuroticism
      interaction, such that the relationship between group and individual undermining
      would be strongest among those simultaneously high in self-esteem and
      neuroticism. The 3-way interaction was supported in Study 1 (457 participants in
      103 groups) and replicated in Study 2 (415 participants in 93 groups) with
      additional controls and alternative measures of key constructs. The authors
      discuss the implications of the research and identify future research directions.

PMID- 16953769
TI  - Does parental job insecurity matter? Money anxiety, money motives, and work
      motivation.
AB  - A structural model focusing on the spillover effect of parental perceived job
      insecurity on money anxiety was developed and tested. The crossover effect of
      parents' money anxiety on their children's money anxiety, money motives, and
      motivation to work was also examined. Data were collected from a sample of
      undergraduates and their parents. Results of structural equation modeling
      analyses supported a spillover effect of paternal perceived job insecurity on
      paternal money anxiety. However, maternal perceived job insecurity was not
      significantly associated with maternal money anxiety. Results also supported a
      crossover effect of parental money anxiety on youths' money anxiety. Youths'
      money anxiety was significantly related to youths' negative money motives. In
      turn, youths' negative money motives were associated with their intrinsic
      motivation to work. Implications of the findings are discussed.

PMID- 16953770
TI  - An examination of the dynamic relationship between self-efficacy and performance
      across levels of analysis and levels of specificity.
AB  - This research used resource allocation theory to generate predictions regarding
      dynamic relationships between self-efficacy and task performance from 2 levels of
      analysis and specificity. Participants were given multiple trials of practice on
      an air traffic control task. Measures of task-specific self-efficacy and
      performance were taken at repeated intervals. The authors used multilevel
      analysis to demonstrate differential and dynamic effects. As predicted, task
      specific self-efficacy was negatively associated with task performance at the
      within-person level. On the other hand, average levels of task-specific self
      efficacy were positively related to performance at the between-persons level and
      mediated the effect of general self-efficacy. The key findings from this research
      relate to dynamic effects--these results show that self-efficacy effects can
      change over time, but it depends on the level of analysis and specificity at
      which self-efficacy is conceptualized. These novel findings emphasize the
      importance of conceptualizing self-efficacy within a multilevel and
      multispecificity framework and make a significant contribution to understanding
      the way this construct relates to task performance.

PMID- 16953771
TI  - Children's identification of faces from lineups: the effects of lineup
      presentation and instructions on accuracy.
AB  - The authors investigated whether the type of lineup and instructions given to
      children 6-7 or 9-10 years of age affected their identification accuracy.
      Children witnessed a man stealing property and were later asked to identify him
      in either photo or video lineups. Some lineups contained the target and some did
      not. Two lineup procedures were used (standard or elimination), and 2 types of
      instruction were used (standard or cautioning about false identification).
      Standard lineups with cautioning instructions decreased target-absent errors with
      no associated reduction in correct identifications, but elimination lineups did
      not. Lineup media had an interaction effect whereby correct identifications were
      reduced in video but not photo elimination lineups. The results are discussed in
      a forensic context.

PMID- 16953772
TI  - A meta-analytic evaluation of the impact of dimension and exercise factors on
      assessment center ratings.
AB  - Two recent reviews have attempted to summarize findings quantitatively regarding
      assessment center (AC) construct-related validity (i.e., Lance, Lambert, Gewin,
      Lievens, & Conway, 2004; Lievens & Conway, 2001). Unlike these previous studies,
      which reanalyzed individual multitrait-multimethod (MTMM) matrices from
      previously published research, the authors recoded and combined past matrices
      into a single MTMM matrix. This matrix, comprised of 6 dimensions each measured
      by 6 exercises, was then analyzed, providing a more generalizable set of results.
      Both dimensions and exercises were found to contribute substantially to AC
      ratings. Specific dimensions (i.e., communication, influencing others, organizing
      and planning, and problem solving) appeared more construct valid than others
      (i.e., consideration/awareness of others and drive). Implications for AC design
      and practice are discussed.

PMID- 16953773
TI  - Abusive supervision and family undermining as displaced aggression.
AB  - This study focuses on factors that contribute to abusive supervision, one form of
      nonphysical aggression, and the results of such abuse on subordinates and their
      family members. Using a "kick the dog" metaphor (As Marcus-Newhall, Pedersen,
      Carlson, and Miller (2000) state, this is a "commonly used anecdote to illustrate
      displaced aggression. . .a man is berated by his boss but does not retaliate
      because he fears losing his job. Hours later, when he arrives home to the
      greeting barks of his dog he responds by kicking it," p. 670), the authors
      investigated whether abusive supervision may be the result of a supervisor's
      displeasure with his or her organization. Using a sample of 210 supervisors,
      their subordinates, and the subordinates' family members or partners, the authors
      hypothesized that supervisors' reports of psychological contract violations,
      moderated by hostile attribution bias, would be associated with subordinates'
      perceptions of abusive supervision. In turn, the authors hypothesized that abused
      subordinates' family members would report sustained negative affect and negative
      evaluations directed toward them in the home. The hypotheses were supported.

PMID- 16953774
TI  - Sources of social support and burnout: a meta-analytic test of the conservation
      of resources model.
AB  - The Conservation of Resources (COR) model of burnout (Hobfoll & Freedy, 1993)
      suggests that resources are differentially related to burnout dimensions. In this
      paper, I provide a meta-analysis of the social support and burnout literature,
      finding that social support, as a resource, did not yield different relationships
      across the 3 burnout dimensions (emotional exhaustion, depersonalization, and
      personal accomplishment), challenging the COR model. However, when considering
      the source of the social support (work vs. nonwork) as a moderator, I found that
      work-related sources of social support, because of their more direct relationship
      to work demands, were more closely associated with exhaustion than
      depersonalization or personal accomplishment; the opposite pattern was found with
      nonwork sources of support. I discuss the implications of this finding in
      relation to the COR model and suggest future research directions to clarify the
      relationship between resources and burnout dimensions.

PMID- 16953775
TI  - When self-efficacy negatively relates to motivation and performance in a learning
      context.
AB  - Recent reviews of the training literature have advocated directly manipulating
      self-efficacy in an attempt to improve the motivation of trainees. However, self
      regulation theories conceive of motivation as a function of various goal
      processes, and assert that the effect of self-efficacy should depend on the
      process involved. Training contexts may evoke planning processes in which self
      efficacy might negatively relate to motivation. Yet the typical between-persons
      studies in the current literature may obscure the effect. To examine this issue,
      63 undergraduate students completed a series of questionnaires measuring self
      efficacy and motivation before 5 class exams. Self-efficacy was negatively
      related to motivation and exam performance at the within-person level of
      analysis, despite a significant positive relation with performance at the between
      persons level.

PMID- 16953776
TI  - Perceptions of organizational change: a stress and coping perspective.
AB  - Few organizational change studies identify the aspects of change that are salient
      to individuals and that influence well-being. The authors identified three
      distinct change characteristics: the frequency, impact and planning of change. R.
      S. Lazarus and S. Folkman's (1984) cognitive phenomenological model of stress and
      coping was used to propose ways that these change characteristics influence
      individuals' appraisal of the uncertainty associated with change, and,
      ultimately, job satisfaction and turnover intentions. Results of a repeated cross
      sectional study that collected individuals' perceptions of change one month prior
      to employee attitudes in consecutive years indicated that while the three change
      perceptions were moderately to strongly intercorrelated, the change perceptions
      displayed differential relationships with outcomes. Discussion focuses on the
      importance of systematically considering individuals' subjective experience of
      change.

PMID- 16953777
TI  - Perceived trustworthiness of knowledge sources: the moderating impact of
      relationship length.
AB  - Prior meta-analytic evidence has indicated no association between relationship
      length and perceived trustworthiness. Viewing trustors as information processors,
      the authors propose a model in which relationship length, although having no
      direct effect on perceived trustworthiness, moderates the association between
      perceived trustworthiness and the basis on which people decide to trust each
      other. Specifically, as trustors learn about others, they base their trust on
      different kinds of information (demographic similarity, trustworthy behavior, and
      shared perspective). Hierarchical multiple regression analyses of a field survey
      of supervisors and subordinates from 3 companies (N = 88) provide evidence
      consistent with this prediction: Perceived trustworthiness is associated with
      demographic similarity in newer relationships, with trustworthy behavior in
      relationships that are neither brand new nor old but in-between, and with shared
      perspective in older relationships.

PMID- 16953778
TI  - A first examination of the relationships between primed subconscious goals,
      assigned conscious goals, and task performance.
AB  - The authors conducted 2 studies of subconscious goal motivation. First, the
      authors ran a pilot study to establish the effects of priming of subconscious
      goals on a performance task frequently used in goal setting research. Second, the
      authors conducted the main study in which the authors examined the effects of
      both priming of subconscious goals and assigned conscious goals on the same
      performance task. The authors found significant main effects of both
      manipulations and a significant interaction between subconscious and conscious
      goals. The effects of conscious difficult and do-best goals were enhanced by
      subconscious goals, although conscious easy goals were not affected. All effects
      from the main study still held after 1 day.

PMID- 16953779
TI  - Video-based versus written situational judgment tests: a comparison in terms of
      predictive validity.
AB  - In this study, the authors examined whether video-based situational judgment
      tests (SJTs) have higher predictive validity than written SJTs (keeping verbal
      content constant). The samples consisted of 1,159 students who completed a video
      based version of an SJT and 1,750 students who completed the same SJT in a
      written format. The study was conducted in a high stakes testing context. The
      video-based version of an interpersonally oriented SJT had a lower correlation
      with cognitive ability than did the written version. It also had higher
      predictive and incremental validity for predicting interpersonally oriented
      criteria than did the written version. In this high stakes context, applicants
      also reacted relatively favorably to the SJTs, although there was no significant
      difference in face validity between the formats. These findings suggest that SJT
      format changes be made with caution and that validation evidence is needed when
      changes are proposed.

PMID- 16953780
TI  - Incidence of Chlamydia infection among asymptomatic women pesented for routine
      Papanicolaou smear: experience in South-Western Victoria, Australia.

PMID- 16953781
TI  - Spatial-pattern-induced evolution of a self-replicating loop network.
AB  - We study a system of self-replicating loops in which interaction rules between
      individuals allow competition that leads to the formation of a hypercycle-like
      network. The main feature of the model is the multiple layers of interaction
      between loops, which lead to both global spatial patterns and local replication.
      The network of loops manifests itself as a spiral structure from which new kinds
      of self-replicating loops emerge at the boundaries between different species. In
      these regions, larger and more complex self-replicating loops live for longer
      periods of time, managing to self-replicate in spite of their slower replication.
      Of particular interest is how micro-scale interactions between replicators lead
      to macro-scale spatial pattern formation, and how these macro-scale patterns in
      turn perturb the micro-scale replication dynamics.

PMID- 16953782
TI  - From machine and tape to structure and function: formulation of a reflexively
      computing system.
AB  - The relationship between structure and function is explored via a system of
      labeled directed graph structures upon which a single elementary read/write rule
      is applied locally. Boundaries between static (information-carrying) and active
      (information-processing) objects, imposed by mandate of the rules or physics in
      earlier models, emerge instead as a result of a structure-function dynamic that
      is reflexive: objects may operate directly on their own structure. A
      representation of an arbitrary Turing machine is reproduced in terms of
      structural constraints by means of a simple mapping from tape squares and machine
      states to a uniform medium of nodes and links, establishing computation
      universality. Exploiting flexibility of the formulation, examples of other
      unconventional "self-computing" structures are demonstrated. A straightforward
      representation of a kinematic machine system based on the model devised by Laing
      is also reproduced in detail. Implications of the findings are discussed in terms
      of their relation to other formal models of computation and construction. It is
      argued that reflexivity of the structure-function relationship is a critical
      informational dynamic in biochemical systems, overlooked in previous models but
      well captured by the proposed formulation.

PMID- 16953783
TI  - The origin of the eukaryotic cell based on conservation of existing interfaces.
AB  - Current theories about the origin of the eukaryotic cell all assume that during
      evolution a prokaryotic cell acquired a nucleus. Here, it is shown that a
      scenario in which the nucleus acquired a plasma membrane is inherently less
      complex because existing interfaces remain intact during evolution. Using this
      scenario, the evolution to the first eukaryotic cell can be modeled in three
      steps, based on the self-assembly of cellular membranes by lipid-protein
      interactions. First, the inclusion of chromosomes in a nuclear membrane is
      mediated by interactions between laminar proteins and lipid vesicles. Second, the
      formation of a primitive endoplasmic reticulum, or exomembrane, is induced by the
      expression of intrinsic membrane proteins. Third, a plasma membrane is formed by
      fusion of exomembrane vesicles on the cytoskeletal protein scaffold. All three
      self-assembly processes occur both in vivo and in vitro. This new model provides
      a gradual Darwinistic evolutionary model of the origins of the eukaryotic cell
      and suggests an inherent ability of an ancestral, primitive genome to induce its
      own inclusion in a membrane.

PMID- 16953784
TI  - Through the interaction of neutral and adaptive mutations, evolutionary search
      finds a way.
AB  - An evolutionary system that supports the interaction of neutral and adaptive
      mutations is investigated. Experimental results on a Boolean function and needle
      in-haystack problems show that this system enables evolutionary search to find
      better solutions faster. Through a novel analysis based on the ratio of neutral
      to adaptive mutations, we identify this interaction as an engine that
      automatically adjusts the relative amounts of exploration and exploitation to
      achieve effective search (i.e., it is self-adaptive). Moreover, a hypothesis to
      describe the search process in this system is proposed and investigated. Our
      findings lead us to counter the arguments of those who dismiss the usefulness of
      neutrality. We argue that the benefits of neutrality are intimately related to
      its implementation, so that one must be cautious about making general claims
      about its merits or demerits.

PMID- 16953785
TI  - Genetic stability and territorial structure facilitate the evolution of tag
      mediated altruism.
AB  - Evolutionary theorists have long been interested in the conditions that permit
      the evolution of altruistic cooperation. Recent work has demonstrated that
      altruistic donation can evolve in surprisingly simple models, in which agents
      base their decisions to donate solely on the similarity of evolved "tags"
      relative to evolved tag-difference tolerances. There is disagreement, however,
      about the conditions under which tag-mediated altruism will in fact evolve. Here
      we vary two critical parameters in a standard model of tag-mediated altruism
      genetic stability and territorial structure-and show that altruism evolves in a
      wide range of conditions. We demonstrate the evolution of significant levels of
      altruism even when the immediate costs to donors equal the benefits to
      recipients. We describe the mechanism that permits the emergence of altruism in
      the model as a form of kin selection that is facilitated by interactions between
      altruism, genetic drift, and fecundity.

PMID- 16953786
TI  - Evolving physically simulated flying creatures for efficient cruising.
AB  - The body-brain coevolution of aerial life forms has not been developed as far as
      aquatic or terrestrial locomotion in the field of artificial life. We are
      studying physically simulated 3D flying creatures by evolving both wing shapes
      and their controllers. A creature's wing is modeled as a number of articulated
      cylinders, connected by triangular films (patagia). The wing structure and its
      motor controllers for cruising flight are generated by an evolutionary algorithm
      within a simulated aerodynamic environment. The most energy-efficient cruising
      speed and the lift and drag coefficients of each flier are calculated from its
      morphological characteristics and used in the fitness evaluation. To observe a
      wide range of creature size, the evolution is run separately for creatures
      categorized into three species by body weight. The resulting creatures vary in
      size from pigeons to pterosaurs, with various wing configurations. We discuss the
      characteristics of shape and motion of the evolved creatures, including flight
      stability and Strouhal number.

PMID- 16953787
TI  - The infection algorithm: an artificial epidemic approach for dense stereo
      correspondence.
AB  - We present a new bio-inspired approach applied to a problem of stereo image
      matching. This approach is based on an artificial epidemic process, which we call
      the infection algorithm. The problem at hand is a basic one in computer vision
      for 3D scene reconstruction. It has many complex aspects and is known as an
      extremely difficult one. The aim is to match the contents of two images in order
      to obtain 3D information that allows the generation of simulated projections from
      a viewpoint that is different from the ones of the initial photographs. This
      process is known as view synthesis. The algorithm we propose exploits the image
      contents in order to produce only the necessary 3D depth information, while
      saving computational time. It is based on a set of distributed rules, which
      propagate like an artificial epidemic over the images. Experiments on a pair of
      real images are presented, and realistic reprojected images have been generated.

PMID- 16953788
TI  - Simulating the hallmarks of cancer.
AB  - Cancer can be viewed as the loss of cooperative cell behaviors that normally
      facilitate multicellularity, including the formation of tissues and organs.
      Hanahan and Weinberg describe the phenotypic differences between healthy and
      cancerous cells in an article titled "The Hallmarks of Cancer" (Cell, 100, 57-70,
      2000). Here the authors propose six phenotypic changes at the cellular level as
      the essential hallmarks of cancer. They investigate the dynamics and interactions
      of these hallmarks in a model known as CancerSim. They describe how CancerSim
      implements the hallmarks in an agent-based simulation which can help test the
      hypotheses put forth by Hanahan and Weinberg. Experiments with CancerSim are
      described that study the interactions of cell phenotype alterations, and in
      particular, the likely sequences of precancerous mutations, known as pathways.
      The experiments show that sequencing is an important factor in tumorigenesis, as
      some mutations have preconditions--they are selectively advantageous only in
      combination with other mutations. CancerSim enables a modeler to study the
      dynamics of a developing tumor and simulate how progression can be altered by
      tuning model parameters.

PMID- 16953792
TI  - Chromatin insulators.
AB  - Active and silenced chromatin domains are often in close juxtaposition to one
      another, and enhancer and silencer elements operate over large distances to
      regulate the genes in these domains. The lack of promiscuity in the function of
      these elements suggests that active mechanisms exist to restrict their activity.
      Insulators are DNA elements that restrict the effects of long-range regulatory
      elements. Studies on different insulators from different organisms have
      identified common themes in their mode of action. Numerous insulators map to
      promoters of genes or have binding sites for transcription factors and like
      active chromatin hubs and silenced loci, insulators also cluster in the nucleus.
      These results bring into focus potential conserved mechanisms by which these
      elements might function in the nucleus.

PMID- 16953793
TI  - Genetic analysis of brain circuits underlying pheromone signaling.
AB  - Molecular approaches and genetic manipulations have provided novel insights into
      the processing of pheromone-mediated information by the olfactory and vomeronasal
      systems of mammals. We will review and discuss the specific contribution of each
      of the two chemosensory systems that ensure specific behavioral responses to
      conspecific animals.

PMID- 16953794
TI  - Motivational and emotional aspects of the self.
AB  - Recent theory and research are reviewed regarding self-related motives (self
      enhancement, self-verification, and self-expansion) and self-conscious emotions
      (guilt, shame, pride, social anxiety, and embarrassment), with an emphasis on how
      these motivational and emotional aspects of the self might be related.
      Specifically, these motives and emotions appear to function to protect people's
      social well-being. The motives to self-enhance, self-verify, and self-expand are
      partly rooted in people's concerns with social approval and acceptance, and self
      conscious emotions arise in response to events that have real or imagined
      implications for others' judgments of the individual. Thus, these motives and
      emotions do not operate to maintain certain states of the self, as some have
      suggested, but rather to facilitate people's social interactions and
      relationships.

PMID- 16953795
TI  - Analysis of nonlinear patterns of change with random coefficient models.
AB  - Nonlinear patterns of change arise frequently in the analysis of repeated
      measures from longitudinal studies in psychology. The main feature of nonlinear
      development is that change is more rapid in some periods than in others. There
      generally also are strong individual differences, so although there is a general
      similarity of patterns for different persons over time, individuals exhibit
      substantial heterogeneity in their particular response. To describe data of this
      kind, researchers have extended the random coefficient model to accommodate
      nonlinear trajectories of change. It can often produce a statistically satisfying
      account of subject-specific development. In this review we describe and
      illustrate the main ideas of the nonlinear random coefficient model with concrete
      examples.

PMID- 16953797
TI  - Moral emotions and moral behavior.
AB  - Moral emotions represent a key element of our human moral apparatus, influencing
      the link between moral standards and moral behavior. This chapter reviews current
      theory and research on moral emotions. We first focus on a triad of negatively
      valenced "self-conscious" emotions-shame, guilt, and embarrassment. As in
      previous decades, much research remains focused on shame and guilt. We review
      current thinking on the distinction between shame and guilt, and the relative
      advantages and disadvantages of these two moral emotions. Several new areas of
      research are highlighted: research on the domain-specific phenomenon of body
      shame, styles of coping with shame, psychobiological aspects of shame, the link
      between childhood abuse and later proneness to shame, and the phenomena of
      vicarious or "collective" experiences of shame and guilt. In recent years, the
      concept of moral emotions has been expanded to include several positive emotions
      elevation, gratitude, and the sometimes morally relevant experience of pride.
      Finally, we discuss briefly a morally relevant emotional process-other-oriented
      empathy.

PMID- 16953796
TI  - Race, race-based discrimination, and health outcomes among African Americans.
AB  - Persistent and vexing health disadvantages accrue to African Americans despite
      decades of work to erase the effects of race discrimination in this country.
      Participating in these efforts, psychologists and other social scientists have
      hypothesized that African Americans' continuing experiences with racism and
      discrimination may lie at the root of the many well-documented race-based
      physical health disparities that affect this population. With newly emerging
      methodologies in both measurement of contextual factors and functional
      neuroscience, an opportunity now exists to cleave together a comprehensive
      understanding of the ways in which discrimination has harmful effects on health.
      In this article, we review emerging work that locates the cause of race-based
      health disparities in the external effects of the contextual social space on the
      internal world of brain functioning and physiologic response. These approaches
      reflect the growing interdisciplinary nature of psychology in general, and the
      field of race relations in particular.

PMID- 16953798
TI  - Inhibition of human betaine-homocysteine methyltransferase expression by S
      adenosylmethionine and methylthioadenosine.
AB  - BHMT (betaine-homocysteine methyltransferase) remethylates homocysteine to form
      methionine. SAM (S-adenosylmethionine) inhibits BHMT activity, but whether SAM
      modulates BHMT gene expression is unknown. Transcriptional regulation of the
      human BHMT is also unknown. The present study examined regulation of the human
      BHMT gene by SAM and its metabolite, MTA (5'-methylthioadenosine). To facilitate
      these studies, we cloned the 2.7 kb 5'-flanking region of the human BHMT gene
      (GenBank accession number AY325901). Both SAM and MTA treatment of HepG2 cells
      resulted in a dose- and time-dependent decrease in BHMT mRNA levels, which
      paralleled their effects on the BHMT promoter activity. Maximal suppression was
      observed with the BHMT promoter construct -347/+33, which contains a number of NF
      kappaB (nuclear factor kappaB) binding sites. SAM and MTA treatment increased NF
      kappaB nuclear binding and NF-kappaB-driven luciferase activities, and increased
      nuclear binding activity of multiple histone deacetylase co-repressors to the NF
      kappaB sites. Overexpression of p50 and p65 decreased BHMT promoter activity,
      while blocking NF-kappaB activation increased BHMT expression and promoter
      activity, and prevented SAM but not MTA's ability to inhibit BHMT expression. The
      NF-kappaB binding site at -301 is responsible, at least in part, for this effect.
      Lower BHMT expression can impair homocysteine metabolism, which can induce ER
      (endoplasmic reticulum) stress. Indeed, MTA treatment resulted in increased
      expression ER stress markers. In conclusion, SAM and MTA down-regulate BHMT
      expression in HepG2 cells in part by inducing NF-kappaB, which acts as a
      repressor for the human BHMT gene. While SAM's mechanism is NF-kappaB-dependent,
      MTA has both NF-kappaB-dependent and -independent mechanisms.

PMID- 16953800
TI  - Collagen binding protein Mip enables Legionella pneumophila to transmigrate
      through a barrier of NCI-H292 lung epithelial cells and extracellular matrix.
AB  - Guinea pigs are highly susceptible to Legionella pneumophila infection and
      therefore have been the preferred animal model for studies of legionellosis. In
      this study guinea pig infections revealed that the Legionella virulence factor
      Mip (macrophage infectivity potentiator) contributes to the bacterial
      dissemination within the lung tissue and the spread of Legionella to the spleen.
      Histopathology of infected animals, binding assays with components of the
      extracellular matrix (ECM), bacterial transmigration experiments across an
      artificial lung epithelium barrier, inhibitor studies and ECM degradation assays
      were used to elucidate the underlying mechanism of the in vivo observation. The
      Mip protein, which belongs to the enzyme family of FK506-binding proteins (FKBP),
      was shown to bind to the ECM protein collagen (type I, II, III, IV, V, VI).
      Transwell assays with L. pneumophila and recombinant Escherichia coli HB101
      strains revealed that Mip enables these bacteria to transmigrate across a barrier
      of NCI-H292 lung epithelial cells and ECM (NCI-H292/ECM barrier). Mip-specific
      monoclonal antibodies and the immunosuppressants rapamycin and FK506, which
      inhibit the peptidyl prolyl cis/trans isomerase (PPIase) activity of Mip, were
      able to inhibit this transmigration. By using protease inhibitors we found that
      the penetration of the NCI-H292/ECM barrier additionally requires a serine
      protease activity. Degradation assays with (35)S-labelled ECM proteins supported
      the finding of a concerted action of Mip and a serine protease. The described
      synergism between the activity of the collagen binding Mip protein and the serine
      protease activity represents an entirely new mechanism for bacterial penetration
      of the lung epithelial barrier and has implications for other prokaryotic and
      eukaryotic pathogens.

PMID- 16953799
TI  - Transmembrane proteins are not required for early stages of nuclear envelope
      assembly.
AB  - All identified membrane fusion proteins are transmembrane proteins. In the
      present study, we explored the post-mitotic reassembly of the NE (nuclear
      envelope). The proteins that drive membrane rearrangements in NE assembly remain
      unknown. To determine whether transmembrane proteins are prerequisite components
      of this fusion machinery, we have focused on nuclear reconstitution in a cell
      free system. Mixing of soluble interphase cytosolic extract and MV (membrane
      vesicles) from amphibian eggs with chromatin results in the formation of
      functional nuclei. We replaced MV and cytosol with protein-free
      phosphatidylcholine LS (liposomes) that were pre-incubated with interphase
      cytosol. While later stages of NE assembly yielding functional nucleus did not
      proceed without integral proteins of MV, LS-associated cytosolic proteins were
      sufficient to reconstitute membrane targeting to the chromatin and GTP-dependent
      lipid mixing. Binding involved LS-associated A-type lamin, and fusion involved
      Ran GTPase. Thus in contrast with post-fusion stages, fusion initiation in NE
      assembly, like membrane remodelling in budding and fission, does not require
      transmembrane proteins.

PMID- 16953801
TI  - Yersinia enterocolitica YopP inhibits MAP kinase-mediated antigen uptake in
      dendritic cells.
AB  - Yersinia enterocolitica (Ye) targets mouse dendritic cells (DCs) and inhibits
      their ability to trigger T cell activation. Here we have investigated whether Ye
      might interfere with antigen presentation in DCs. Infection of DCs with the Ye
      wild-type strain reduced OVA uptake by DCs as demonstrated by flow cytometry and
      confocal laser scan microscopy. In contrast, DCs infected with Yersinia outer
      protein P (YopP)-deficient mutant strain rapidly internalized OVA. Furthermore,
      transfection of DCs with YopP, but not with a cysteine protease deficient YopP
      C172A mutant, reduced uptake of OVA. This finding suggests that YopP, a virulence
      factor of Ye, inhibits OVA uptake by DCs. By the use of MAPK inhibitors we
      provide evidence that YopP mediates reduction of OVA uptake by its ability to
      block MAPK signalling pathways in host cells. Using transferrin (Tf) as specific
      marker for clathrin-mediated endocytosis (CME) and lucifer yellow (LY) as
      specific marker for macropinocytosis (MP) we could show that YopP inhibits CME,
      whereas other Yops inhibit MP. In keeping with these data, activation and
      proliferation of OVA-specific T cells was reduced when DCs were treated with MAPK
      inhibitors. Together, our data demonstrate that (i) MAPK play an important role
      in antigen uptake by CME in DCs, and (ii) that YopP inhibits this pathway of
      antigen uptake in DCs, which might contribute to evasion of adaptive immunity.

PMID- 16953802
TI  - Real-time studies of the progression of bacterial infections and immediate tissue
      responses in live animals.
AB  - By combining intravital multiphoton microscopy and bacterial genetics we have
      developed a technique enabling real-time imaging of bacterial proliferation and
      tissue responses in a live animal. Spatial and temporal control of the infection
      process was achieved by microinjecting GFP(+)-expressing uropathogenic
      Escherichia coli (UPEC) into tubules of exteriorized kidneys in live rats. GFP(+)
      was introduced in the clinical UPEC strain CFT073 as a single-copy chromosomal
      gene fusion. Within hours, bacterial colonization was accompanied by marked
      ischaemic effects, perivascular leakage, loss of tubular integrity and localized
      recruitment of immune cells. The pathophysiology was altered in response to an
      isogenic bacterial strain lacking the exotoxin haemolysin, revealing the subtle
      and temporal roles of bacterial virulence factors in vivo. Microdissection and
      RNA extraction of the injected nephron allowed molecular analysis of prokaryotic
      and eukaryotic gene expression. The techniques described here can be applied to
      study the integrated cell communication evoked by a variety of bacterial
      pathogens, assisting in the design of strategies to combat bacterial infections.

PMID- 16953803
TI  - Kupffer cells are obligatory for Plasmodium yoelii sporozoite infection of the
      liver.
AB  - Previous studies suggested Plasmodium sporozoites infect hepatocytes after
      passing through Kupffer cells, but proof has been elusive. Here we present new
      information strengthening that hypothesis. We used homozygous op/op mice known to
      have few Kupffer cells because they lack macrophage colony stimulating factor 1
      required for macrophage maturation due to a deactivating point mutation in the
      osteopetrosis gene. We found these mice to have 77% fewer Kupffer cells and to
      exhibit reduced clearance of colloidal carbon particles compared with
      heterozygous phenotypically normal littermates. Using a novel quantitative
      reverse transcription polymerase chain reaction assay for P. yoelii 18S rRNA, we
      found liver infection of op/op mice to be decreased by 84% compared with
      controls. However, using another way of limiting Kupffer cells, treatment with
      liposome-encapsulated clodronate, infection of normal mice was enhanced seven- to
      15-fold. This was explained by electron microscopy showing temporary gaps in the
      sinusoidal cell layer caused by this treatment. Thus, Kupffer cell deficiency in
      op/op mice decreases sporozoite infection by reducing the number of portals to
      the liver parenchyma, whereas clodronate increases sporozoite infection by
      opening portals and providing direct access to hepatocytes. Together these data
      provide strong support for the hypothesis that Kupffer cells are the portal for
      sporozoites to hepatocytes and critical for the onset of a malaria infection.

PMID- 16953804
TI  - Phagocytosis of Aspergillus fumigatus conidia by murine macrophages involves
      recognition by the dectin-1 beta-glucan receptor and Toll-like receptor 2.
AB  - Aspergillus fumigatus is a fungal pathogen causing severe infections in
      immunocompromised patients. For clearance of inhaled conidia, an efficient
      response of the innate immune system is required. Macrophages represent the first
      line of defence and ingest and kill conidia. C-type lectins represent a family of
      receptors, which recognize pathogen-specific carbohydrates. One of them is beta1
      3 glucan, a major component of the fungal cell wall. Here we provide evidence
      that beta1-3 glucan plays an important role for the elimination of A. fumigatus
      conidia. Laminarin, a soluble beta1-3 glucan and antibodies to dectin-1, a well
      known beta1-3 glucan receptor, significantly inhibited conidial phagocytosis. On
      resting conidia low amounts of surface accessible beta1-3 glucan were detected,
      whereas high amounts were found on small spores that appear early during
      germination and infection as well as on resting conidia of a pksP mutant strain.
      Swollen conidia also display larger quantities of beta1-3 glucan, although in an
      irregular spotted pattern. Resting pksP mutant conidia and swollen wild-type
      conidia are phagocytosed with high efficiency thereby confirming the relevance of
      beta1-3 glucans for conidial phagocytosis. Additionally we found that TLR2 and
      the adaptor protein MyD88 are required for efficient conidial phagocytosis,
      suggesting a link between the TLR2-mediated recognition of A. fumigatus and the
      phagocytic response.

PMID- 16953805
TI  - Mutational analysis of human CEACAM1: the potential of receptor polymorphism in
      increasing host susceptibility to bacterial infection.
AB  - A common overlapping site on the N-terminal IgV-like domain of human
      carcinoembryonic antigen (CEA)-related cell adhesion molecules (CEACAMs) is
      targeted by several important human respiratory pathogens. These include
      Neisseria meningitidis (Nm) and Haemophilus influenzae (Hi) that can cause
      disseminated or persistent localized infections. To define the precise structural
      features that determine the binding of distinct pathogens with CEACAMs, we have
      undertaken molecular modelling and mutation of the receptor molecules at
      previously implicated key target residues required for bacterial binding. These
      include Ser-32, Tyr-34, Val-39, Gln-44 and Gln-89, in addition to Ile-91, the
      primary docking site for the pathogens. Most, but not all, of these residues
      located adjacent to each other in a previous N-domain model of human CEACAM1,
      which was based on REI, CD2 and CD4. In the current studies, we have refined this
      model based on the mouse CEACAM1 crystal structure, and observe that all of the
      above residues form an exposed continuous binding region on the N-domain.
      Examination of the model also suggested that substitution of two of these
      residues 34 and 89 could affect the accessibility of Ile-91 for ligand binding.
      By introducing selected mutations at the positions 91, 34 and 89, we confirmed
      the primary importance of Ile-91 in all bacterial binding to CEACAM1 despite the
      inter- and intraspecies structural differences between the bacterial CEACAM
      binding ligands. The studies further indicated that the efficiency of binding was
      significantly enhanced for specific strains by mutations such as Y34F and Q89N,
      which also altered the hierarchy of Nm versus Hi strain binding. These studies
      imply that distinct polymorphisms in human epithelial CEACAMs have the potential
      to decrease or increase the risk of infection by the receptor-targeting
      pathogens.

PMID- 16953807
TI  - "Health courts" and accountability for patient safety.
AB  - Proposals that medical malpractice claims be removed from the tort system and
      processed in an alternative system, known as administrative compensation or
      "health courts," attract considerable policy interest during malpractice
      "crises," including the current one. This article describes current proposals for
      the design of a health court system and the system's advantages for improving
      patient safety. Among these advantages are the cultivation of a culture of
      transparency regarding medical errors and the creation of mechanisms to gather
      and analyze data on medical injuries. The article discusses the experiences of
      foreign countries with administrative compensation systems for medical injury,
      including their use of claims data for research on patient safety; choices
      regarding the compensation system's relationship to physician disciplinary
      processes; and the proposed system's possible limitations.

PMID- 16953808
TI  - Promoting declines in the prevalence of late-life disability: comparisons of
      three potentially high-impact interventions.
AB  - Although the prevalence of late-life disability has been declining, how best to
      promote further reductions remains unclear. This article develops and then
      demonstrates an approach for comparing the effects of interventions on the
      prevalence of late-life disability. We review evidence for three potentially high
      impact strategies: physical activity, depression screening and treatment, and
      fall prevention. Because of the large population at risk for falling, the
      demonstrated efficacy of multi-component interventions in preventing falls, and
      the strong links between falls and disability, we conclude that, in the short
      run, multi-component fall-prevention efforts would likely have a higher impact
      than either physical activity or depression screening and treatment. However,
      longer-term comparisons cannot be made based on the current literature and may
      differ from short-run conclusions, since increases in longevity may temper the
      influences of these interventions on prevalence. Additional research is needed to
      evaluate longer-term outcomes of interventions, including effects on length and
      quality of life.

PMID- 16953809
TI  - A tale of two counties: expanding health insurance coverage for children in
      California.
AB  - During difficult economic times, many California counties have expanded health
      insurance coverage for low-income children. These Children's Health Initiatives
      (CHIs) enroll children in public programs and provide new health insurance,
      Healthy Kids, for those ineligible for existing programs. This article describes
      the policy issues in implementing the Santa Clara and San Mateo County CHIs, as
      well as the children's enrollment levels and utilization of services. These CHIs
      are among the first of the thirty California counties planning or implementing
      such initiatives. Their success depends on leadership from county agencies that
      have not traditionally worked closely together, as well as the development of a
      diverse public and private funding base. This effort to provide universal
      coverage for all children is important to national policymakers desiring similar
      goals.

PMID- 16953810
TI  - The effect of substance abuse treatment on Medicaid expenditures among general
      assistance welfare clients in Washington state.
AB  - Little is currently known about the effect of substance abuse treatment on
      Medicaid expenses and other health care costs for welfare clients. This study
      examined the association between substance abuse treatment and reductions in
      medical care expenditures (primarily Medicaid expenses) for General Assistance
      (GA) welfare clients in Washington State. The treatment group included 3,235 GA
      clients who received treatment during 2000 or 2001. The comparison group included
      4,863 GA clients who needed substance abuse treatment but did not receive it.
      Substance abuse treatment was associated with a reduction (p < .01) in medical
      expenses of approximately 2,500 US dollars annually. This estimated savings
      equaled the cost of treatment and represented approximately 35 percent of the
      annual Medicaid expenses incurred by GA clients with substance abuse problems.

PMID- 16953811
TI  - Developing an evidence base for policies and interventions to address health
      inequalities: the analysis of "public health regimes".
AB  - Systematic reviews have become an important methodology in the United Kingdom by
      which research informs health policy, and their use now extends beyond evidence
      based medicine to evidence-based public health and, particularly, health
      inequalities policies. This article reviews the limitations of systematic reviews
      as stand-alone tools for this purpose and suggests a complementary approach to
      make better use of the evidence. That is, systematic reviews and other sources of
      evidence should be incorporated into a wider analytical framework, the public
      health regime (defined here as the specific legislative, social, political, and
      economic structures that have an impact on both public health and the
      appropriateness and effectiveness of public health interventions adopted). At the
      national level this approach would facilitate analysis at all levels of the
      policy framework, countering the current focus on individual interventions. It
      could also differentiate at the international level between those policies and
      interventions that are effective in different contexts and are therefore
      potentially generalizable and those that depend on particular conditions for
      success.

PMID- 16953812
TI  - Fundamental mechanisms of host immune responses to infection.
AB  - Chronic inflammatory periodontal disease is caused by host immune responses to
      periodontal microorganisms. Although periodontal disease seems to progress
      locally in the oral cavity, the actual immune responses proceed at two sites, one
      being the local area peripheral to the periodontium, and the other being in
      secondary lymphoid tissues, such as lymph nodes and the spleen. To investigate
      the pathogenesis of periodontal diseases, it is essential to understand exactly
      how the immune system works against microbial infections. The past decade has
      produced remarkable advances in our understanding of host immune responses. This
      review highlights two of these developments: cross-talk between innate and
      adaptive immunity mediated by dendritic cells via toll-like receptors; and
      antigen-specific immune regulation by dendritic cells and T cells.

PMID- 16953813
TI  - Signal transduction pathways involved in the stimulation of tissue type
      plasminogen activator by interleukin-1alpha and Porphyromonas gingivalis in human
      osteosarcoma cells.
AB  - BACKGROUND: Recently, evidences have shown that tissue type plasminogen activator
      (t-PA) may play an important role in the pathogenesis of periodontal diseases.
      However, the mechanisms and signal transduction pathways involved in the
      production of t-PA in human osteosarcoma cells are not fully understood.
      OBJECTIVES: The purpose of this study was to investigate the caseinolytic
      activity in human osteosarcoma cell line U2OS cells stimulated with interleukin
      1alpha (IL-1alpha) or Porphyromonas gingivalis in the absence or presence of p38
      inhibitor SB203580, mitogen-activated protein kinase kinase (MEK) inhibitor
      U0126, and phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. METHODS: IL
      1alpha and the supernatants of P. gingivalis were used to evaluate the
      caseinolytic activity in U2OS cells by using casein zymography and enzyme-linked
      immunosorbent assay (ELISA). Furthermore, to search possible signal transduction
      pathways, SB203580, U0126, and LY294002 were added to test how they modulated the
      caseinolytic activity. RESULTS: Casein zymography exhibited a caseinolytic band
      with a molecular weight of approximately 70 kDa, suggestive of the presence of t
      PA. Secretion of t-PA was found to be stimulated with IL-1alpha and P. gingivalis
      during a 2-day culture period (p < 0.05). From the results of casein zymography
      and ELISA, SB203580, U0126, and LY294002 significantly reduced the IL-1alpha or
      P. gingivalis-stimulated t-PA production, respectively (p < 0.05). CONCLUSIONS:
      Our findings demonstrated that IL-1alpha and P. gingivalis enhance t-PA
      production in human osteosarcoma cells, and that the signal transduction pathways
      p38, MEK, and PI3K are involved in the inhibition of t-PA. SB203580, U0126, and
      LY294002 suppress t-PA production and/or activity and may therefore be valuable
      therapeutics in t-PA-mediated periodontal destruction, and might be proved
      clinically useful agents, in combination with standard treatment modalities, in
      the treatment of periodontitis.

PMID- 16953814
TI  - Effect of Er:YAG and Diode lasers on the adhesion of blood components and on the
      morphology of irradiated root surfaces.
AB  - OBJECTIVE: The aim of this study was to evaluate in vitro, by scanning electron
      microscopy (SEM), the adhesion of blood components on root surfaces irradiated
      with Er:YAG (2.94 microm) and GaAlAs Diode (808 nm) lasers and the effects on the
      morphology of irradiated root surfaces. METHODS: One hundred samples of human
      teeth were obtained. They were previously planed and scaled with manual
      instruments and divided into five groups of 20 samples each: G1 (control group) -
      absence of treatment; G2--Er:YAG laser (7.6 J/cm2); G3--Er:YAG laser (12.9
      J/cm2); G4--Diode laser (90 J/cm2) and G5--Diode laser (108 J/cm2). After these
      treatments, 10 samples of each group received a blood tissue but the remaining 10
      did not. After laboratory treatments, the samples were obtained by SEM, the
      photomicrographs were analysed by the score of adhesion of blood components and
      the results were statistically analysed (Kruskall-Wallis and Mann-Whitney test).
      RESULTS: In relation to the adhesion of blood components, the study showed no
      significant differences between the control group and the groups treated with
      Er:YAG laser (p = 0.9633 and 0.6229). Diode laser radiation was less effective
      than control group and Er:YAG laser radiation (p < 0.01). CONCLUSIONS: None of
      the proposed treatments increased the adhesion of blood components in a
      significant way when compared to the control group. Although the Er:YAG laser did
      not interfere in the adhesion of blood components, it caused more changes on the
      root surface, whereas the Diode laser inhibited the adhesion.

PMID- 16953815
TI  - Evidence for a specific crevicular lymphocyte profile in aggressive
      periodontitis.
AB  - BACKGROUND AND OBJECTIVE: It is undisputed that the periodontal pocket is a
      particular region of the host defense that is dominated by polymorphonuclear
      leukocytes. However, little is known about the lymphocytes in the crevice. It was
      the aim of this study to analyse the proportions of T cells (CD3+), T-helper
      cells (CD4+), T-suppressor cells (CD8+), and B cells (CD20+) in the crevice of
      patients with localized aggressive periodontitis (LAP), generalized aggressive
      periodontitis (GAP), and generalized chronic periodontitis (CP). The results were
      compared with those obtained from periodontally healthy controls. MATERIAL AND
      METHODS: Crevicular cells were collected according to a previously described
      method. The lymphocyte subpopulations were analysed by using an indirect
      immunofluorescence method. RESULTS: Significant differences were established
      between the test groups and the controls regarding the mean number of CD8+
      lymphocytes (LAP > CP and controls; p < 0.05) and CD20+ lymphocytes (LAP/GAP >
      CP, p < 0.05 and LAP/GAP > controls; p < 0.001). Significant variations in the
      CD4+/CD8+ ratio were observed (LAP < controls and GAP < controls; p < 0.01), as
      well as a correlation between the number of T cells and the degree of
      inflammation. CONCLUSION: In the present study, patients with LAP and patients
      with GAP were found to have increased numbers of crevicular T
      suppressor/cytotoxic and B cells. This supports the hypothesis of a changed
      immune pathology in patients with aggressive periodontitis.

PMID- 16953816
TI  - Evaluation of RANK/RANKL/OPG gene polymorphisms in aggressive periodontitis.
AB  - BACKGROUND AND OBJECTIVE: Aggressive periodontitis (AgP) is a specific type of
      periodontal disease that is characterized by rapid attachment loss and bone
      destruction. While attempting to identify genetic polymorphisms associated with
      AgP, previous research has focused on candidate genes that may be involved in
      immune responses to microbial infections. In this study, the focus was on single
      nucleotide polymorphisms (SNPs) in the key mediators of osteoclast
      differentiation and activation, which involve receptor activator of nuclear
      factor-kappaB (RANK), RANK ligand (RANKL) and osteoprotegrin (OPG), in the
      Japanese population. The aim of this study was to evaluate the association of
      RANK/RANKL/OPG gene polymorphisms with AgP in the Japanese population. MATERIAL
      AND METHODS: We examined 99 patients with AgP and 89 controls from the Japanese
      population to explore the possibility of RANK/RANKL/OPG loci as candidate regions
      associated with the disease. All exons and relevant exon-intron boundaries of
      these three candidate genes were amplified by polymerase chain reaction (PCR)
      using 19 primers, followed by direct sequencing. The polymorphisms were
      identified by comparing the sequences obtained from 48 subjects. RESULTS: We
      identified 27 SNPs in RANK, including 10 novel SNPs and seven SNPs each in both
      RANKL and OPG. A pairwise linkage disequilibrium analysis using the r2 statistic
      showed that some SNP pairs from the three loci are in tight linkage
      disequilibrium. CONCLUSION: An association analysis with allelotypes showed that
      SNPs identified in the RANK/RANKL/OPG genes have no significant association with
      AgP in the Japanese population.

PMID- 16953817
TI  - Levels of lipid peroxides and antioxidants in smokers and nonsmokers.
AB  - BACKGROUND AND OBJECTIVE: The aim of the study was to evaluate the relationship
      between cigarette smoking and periodontal damage in terms of the levels of free
      radicals and antioxidants. MATERIAL AND METHODS: Thirty-five healthy subjects in
      the age group 25-56 yr and with chronic moderate inflammatory periodontal disease
      (attachment loss of 3-4 mm) were selected. All subjects were matched with respect
      to the clinical parameters plaque index, gingival index and attachment loss. Of
      the 35 subjects, 25 were smokers (smoking a minimum of 15 cigarettes/day) and 10
      were nonsmokers. Smokers were subdivided into three subgroups: group I (10
      subjects smoking 15-20 cigarettes/day); group II (10 subjects smoking 21-30
      cigarettes/day) and group III (five subjects smoking > 50 cigarettes/day).
      Gingival tissue (obtained during Modified Widman surgery) and blood samples were
      collected from each of the subjects and analyzed for the following parameters:
      lipid peroxide, superoxide dismutase, catalase, glutathione and total thiol.
      RESULTS: The level of lipid peroxide was lowest in nonsmokers (2.242 +/- 0.775 in
      tissue and 1.352 +/- 0.414 in blood) and highest in smokers smoking > 50
      cigarettes/day (6.81 +/- 1.971 in tissue and 4.96 +/- 0.890 in blood), both in
      tissue and in blood. The increase was statistically significant in all groups,
      except in tissue of group I smokers. Catalase showed a similar trend, where the
      levels increased from 0.245 +/- 0.043 in controls to 0.610 +/- 0.076 in group III
      smokers for tissue, and from 0.231 +/- 0.040 in controls to 0.568 +/- 0.104 in
      group III smokers for blood. The increase was statistically significant for all
      groups. Total thiol levels were also higher in smokers than in controls (0.222 +/
      0.050 in controls vs. 0.480 +/- 0.072 in group III smokers in tissue; 0.297 +/-
      0.078 in controls vs. 0.617 +/- 0.042 in group III smokers in blood). Except for
      group I in both tissue and blood, the increase was statistically significant. The
      superoxide dismutase (SOD) level was higher in nonsmokers (2.406 +/- 0.477 in
      tissue and 2.611 +/- 0.508 in blood) than in group III smokers (1.072 +/- 0.367
      in tissue and 0.938 +/- 0.367 in blood), both in tissue and in blood, but this
      was significant only in the case of blood and for group III smokers in tissue.
      The glutathione level in tissue was consistently lower in smokers than in
      controls, showing a decrease from 121.208 +/- 37.367 in controls to 46.426 +/-
      14.750 in group III smokers, but the decrease was not significant in group I
      smokers. In the case of blood, the glutathione level dropped from 262.074 +/-
      68.751 in controls to 154.242 +/- 51.721 in group III smokers, but was
      statistically significant only for group III smokers. CONCLUSION: The study
      results show that smoking increases the level of free radicals in periodontal
      tissues, which in turn may be responsible for the destruction seen in periodontal
      diseases.

PMID- 16953818
TI  - Levels of matrix metalloproteinases-8 and -9 with simultaneous presence of
      periodontal pathogens in gingival crevicular fluid as well as matrix
      metalloproteinase-9 and cholesterol in blood.
AB  - BACKGROUND AND OBJECTIVES: To investigate the levels of matrix metalloproteinase
      (MMP) -8 and -9 with the simultaneous presence of periodontal pathogens in
      gingival crevicular fluid (GCF) as well as MMP-9 and cholesterol in blood.
      Although bacterial pathogens are required to initiate the periodontal disease
      process, in some individuals the reaction to bacteria may lead to an excessive
      host response, resulting in a general inflammatory response. METHODS: MMP-9 and
      lipids were analyzed from the blood samples of 33 subjects with a 16-year history
      and oral health records of periodontal disease as well as from 31 periodontally
      healthy controls. Information was obtained on education, body mass index, and
      family history of atherosclerosis. GCF was taken to determine MMP-8 and MMP-9
      levels, and bacterial samples were simultaneously collected for polymerase chain
      reaction assessment of Actinobacillus actinomycetemcomitans, Porphyromonas
      gingivalis, Prevotella intermedia, Prevotella nigrescens, Tannerella forsythia,
      and Treponema denticola. Analysis of variance, chi-squared test, and multiple
      logistic regression analysis were used to analyze the results. RESULTS:
      Demographic data showed significant differences between patients and controls in
      smoking (P < 0.01), body mass index (P < 0.05), family history of atherosclerotic
      disease (P < 0.01), and education (P < 0.01). Significant differences were also
      observed in oral health data, in the detection of P. gingivalis (P < 0.001), P.
      intermedia (P < 0.01), P. nigrescens (P < 0.001), and T. forsythia (P < 0.001)
      and in the levels of MMP-8 and MMP-9 in GCF between patients and controls. T.
      forsythia[odds ratio(OR) 10.1; P = 0.001] and age (OR 5.54; P = 0.008) appeared
      to be the main independent predictors for high MMP-8 in GCF. Patients had
      significantly higher total cholesterol (P < 0.01), low-density lipoprotein
      cholesterol (P = 0.05), and triglycerides (P < = 0.01) than controls. Plasma
      levels of MMP-9 were significantly higher in patients than in controls (P =
      0.001). CONCLUSIONS: Specific periodontal microorganisms appeared to induce host
      response, with increased release of MMP-8 and MMP-9 in gingival pockets as well
      as of MMP-9 in plasma, possibly triggering its up-regulation in blood.

PMID- 16953819
TI  - Induction of the myofibroblastic phenotype in human gingival fibroblasts by
      transforming growth factor-beta1: role of RhoA-ROCK and c-Jun N-terminal kinase
      signaling pathways.
AB  - BACKGROUND AND OBJECTIVES: Myofibroblastic differentiation is an important event
      in gingival wound healing and chronic inflammation. Transforming growth factor
      beta 1 (TGF-beta1) is a potent growth factor that has been implicated in this
      process. Gingival myofibroblasts have an increased ability to remodel the
      extracellular matrix and this feature has been associated with changes in the
      distribution of F-actin and the expression of the myofibroblast marker alpha
      smooth muscle actin. In the present study we have analyzed the role of TGF-beta1
      and the signaling routes activated by this factor in the cytoskeletal changes
      that characterize the myofibroblastic differentiation process in human gingival
      fibroblasts. MATERIALS AND METHODS: The signalling pathways involved in
      myofibroblastic differentiation were studied in primary cultures of human
      gingival fibroblasts using several signal transduction inhibitors. RhoA
      activation was analyzed through a pull-down assay. Distribution of focal
      adhesions and actin cytoskeleton was assessed by means of immunofluorescence and
      western blot. A cell adhesion assay was performed in TGF-beta1-stimulated cells.
      Smooth muscle actin expression was studied through western blot and
      immunofluorescence. c-Jun N-terminal kinase phosphorylation was assessed through
      western blot. RESULTS: Our observations show that TGF-beta1 activated the GTPase
      RhoA, a key regulator of the actin cytoskeleton. As a consequence of this event,
      this growth factor stimulated the generation of actin stress fibers and the
      reinforcement of vinculin-enriched focal adhesions. These responses were blocked
      after inhibiting ROCK, the main target of RhoA activation. TGF-beta1 also
      stimulated the adhesion of fibroblasts over fibronectin, an extracellular matrix
      molecule involved in myofibroblastic differentiation. Finally, induction of the
      myofibroblast marker alpha-smooth muscle actin by TGF-beta1 was abolished by the
      c-Jun N-terminal protein kinase inhibitor SP600125, suggesting a role for this
      signaling pathway during the induction of this phenotype. CONCLUSIONS: We propose
      that TGF-beta1 may promote the differentiation of myofibroblasts through the
      stimulation of cell spreading and adhesion, the reinforcement of focal adhesions,
      the maturation of the actin cytoskeleton, and the induction of alpha-smooth
      muscle actin. Activity of RhoA-ROCK and c-Jun N-terminal protein kinase signaling
      pathways are probably involved in these cellular events.

PMID- 16953820
TI  - Analysis of interleukin-1beta-modulated mRNA gene transcription in human gingival
      keratinocytes by epithelia-specific cDNA microarrays.
AB  - BACKGROUND/OBJECTIVES: Proinflammatory cytokines such as interleukin-1beta are
      known to be synthesized in oral gingivitis and periodontitis and lead to the
      activation of the transcription factor nuclear factor-kappaB (NF-kappaB).
      Although numerous effects of interleukin-1beta on mesenchymal cells are known,
      e.g. up-regulation of intercellular adhesion molecule-1 in endothelial cells,
      little is known of the effects of interleukin-1beta on oral keratinocytes. The
      purpose of the present study was to seek interleukin-1beta-mediated alterations
      in mRNA gene transcription and a putative activation of NF-kappaB in oral
      gingival keratinocytes. METHODS: As an in vitro model for gingivitis and
      periodontitis, immortalized human gingival keratinocytes (IHGK) were stimulated
      with the proinflammatory cytokine interleukin-1beta. An epithelia-specific cDNA
      microarray was used to analyze mRNA expression profiles from IHGK cells treated
      with 200 units interleukin-1beta/ml for 3, 6, 9, 12, and 24 h. Indirect
      immunofluorescence was carried out to detect NF-kappaB in IHGK following
      interleukin-1beta treatment. RESULTS: Detailed analysis revealed distinct
      patterns of time-dependent changes, including genes induced or repressed early (3
      6 h) or late (12-24 h) after interleukin-1beta treatment. Differentially
      expressed genes were involved in (i) cell stress, (ii) DNA repair, (iii) cell
      cycle and proliferation, (iv) anti-pathogen response, (v) extracellular matrix
      turnover, and (vi) angiogenesis. A large number of genes were responsive to NF
      kappaB and induction was concomitant with nuclear translocation of the p65 RelA
      subunit of NF-kappaB. Interestingly, many of these genes contain multiple NF
      kappaB binding sites in their promoters. CONCLUSION: Analysis of altered gene
      expression allows identification of gene networks associated with inflammatory
      responses. In addition to a number of well-known genes involved in gingivitis and
      periodontitis, we identified novel candidates that might be associated with the
      onset and maintenance of an inflammatory disease.

PMID- 16953821
TI  - Differences in innate immune responses upon stimulation with gram-positive and
      gram-negative bacteria.
AB  - BACKGROUND AND OBJECTIVES: Host recognition pathways for gram-negative and gram
      positive bacteria comprise pattern recognition receptors among which Toll-like
      receptors (TLRs) play a pivotal role. TLRs share common signaling pathways yet
      exhibit specificity as well. Periodontal disease is initiated and maintained in
      the first line by gram-negative but also gram-positive bacterial infection of the
      gingival sulcus. To date only limited information is available on whether gram
      positive and gram-negative bacteria induce different host responses (strength or
      quality). MATERIALS AND METHODS: To elucidate these differential effects we
      focused on proinflammatory cytokine releases by assessing ex vivo stimulation of
      whole blood with heat-killed gram-negative and gram-positive bacteria and thereof
      derived microbial products associated with distinct TLRs. Tumor necrosis factor
      alpha and interleukin-8 release were measured in the supernatants by enzyme
      linked immunosorbent assay. In addition, innate immune responses of peritoneal
      macrophages from mice lacking TLR2 and TLR4 were tested. RESULTS: We observed
      that gram-negative and gram-positive species induced distinct patterns of
      cytokine production. Gram-negative species produced higher amounts of tumor
      necrosis factor-alpha while gram-positive species released higher amounts of the
      chemokine interleukin-8. Data from TLR knockout mice and TLR-transfected HEK
      cells revealed a somehow specific role of TLR4 and TLR2 for the recognition of
      gram-negative and gram-positive bacteria, respectively, an observation that goes
      along with the dominant recognition of the respective pathogen associated
      molecular patterns lipopolysaccharide and lipoteichoic acid. CONCLUSIONS: The
      results show that gram-negative and gram-positive bacterial species induce
      different patterns of immunoregulatory activity, which might be the result of
      activation of different TLRs.

PMID- 16953822
TI  - Platelet-rich plasma/osteoblasts complex induces bone formation via osteoblastic
      differentiation following subcutaneous transplantation.
AB  - BACKGROUND AND OBJECTIVE: Platelet-rich plasma (PRP) has been shown to enhance
      the maturation of bone grafts following local application and to have biological
      effects on osteoblasts in vitro. However, PRP is not applied by itself clinically
      as a result of its poor benefits in large bone defects. The present study was
      undertaken to develop a clinical alternative to autologous bone, by investigating
      the application of PRP in combination with osteoblastic cells and evaluating its
      effects after transplantation. MATERIAL AND METHODS: PRP and platelet-poor plasma
      (PPP) were prepared from blood, obtained from ddY mice, by two centrifugation
      steps. MC3T3-E1 cells were labeled with fluorescent carbocyanine just before
      transplantation. The combination of labeled cells and PRP gel was subcutaneously
      transplanted into the back of severe combined immunodeficient (SCID) mice, and
      the transplants were evaluated radiographically and immunohistologically after 4
      wk. The effects of PRP were assessed by alkaline phosphatase (ALP) staining and
      von Kossa staining, and the expression of bone-related markers was analyzed by
      reverse transcription-polymerase chain reaction before transplantation. RESULTS:
      Before transplantation, PRP enhanced the expression of Osterix and bone
      sialoprotein mRNAs compared with PPP. Furthermore, PRP elevated ALP activity and
      induced the formation of mineralized nodules. After transplantation, the
      combination of labeled cells and PRP gel formed mineralized tissue, and the
      transplanted cells visualized in the tissue using fluorescence microscopy
      expressed osteocalcin and type I collagen. CONCLUSION: These results suggest that
      the application of a PRP/osteoblasts complex has beneficial effects for
      transplanting engineered cells into bone defects through the promotion of
      osteoblastic differentiation.

PMID- 16953823
TI  - Chemically modified tetracyclines stimulate matrix metalloproteinase-2 production
      by periodontal ligament cells.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this study was to investigate the
      effects of chemically modified tetracyclines (CMTs) on the production of
      gelatinases [matrix metalloproteinase (MMP)-2 and -9] by human periodontal
      ligament (PDL) cells, and on the activity of recombinant gelatinases. MATERIAL
      AND METHODS: Human PDL cells were cultured with CMT-1, -3, -5, -7 or -8 in
      concentrations of 0, 1, 5, 10, 20, 50, 100, 200 and 500 microm. Gelatin
      zymography was used to determine MMP-2 and -9 production of the cells. The amount
      of DNA present in the cultures was analyzed using a fluorescent assay. The
      cytotoxicity of the CMTs was also determined. Recombinant human MMP-2 and -9 were
      incubated with the CMTs (0-500 microm) and their activity was analyzed using an
      internally quenched fluorogenic substrate. RESULTS: MMP-2 production was
      stimulated up to sevenfold by CMT-1, -3, -7 and -8 at low concentrations (10-200
      microm). No significant amounts of MMP-9 were produced. In contrast, MMP-2 and -9
      activity was reduced by approximately 10-40-fold at higher concentrations (200
      500 microm). CMT-5 had no effect on the production or on the activity of MMP-2
      and -9. Only CMT-3 and -8 had cytotoxic effects on the PDL cells at the highest
      concentrations. CONCLUSION: Surprisingly, CMTs are able to stimulate MMP-2
      production at relatively low concentrations. However, at higher concentrations
      they exert a much stronger inhibitory effect on gelatinase activity. A possible
      stimulatory effect of CMTs on MMP production should be considered in their
      clinical use.

PMID- 16953824
TI  - The effect of Emdogain on the growth and differentiation of rat bone marrow
      cells.
AB  - BACKGROUND AND OBJECTIVE: The major extracellular matrix (ECM) proteins in
      developing enamel can induce and maintain the formation and mineralization of
      other skeletal hard tissue, such as bone. Therefore, dental matrix proteins are
      ideal therapeutic agents when direct formation of functional bone is required for
      a successful clinical outcome. Emdogain (EMD) consists of enamel matrix proteins
      which are known to stimulate bone formation. However, only a few studies in the
      literature have reported the effect of EMD on osteoblast-like cells in vitro.
      MATERIAL AND METHODS: In this study, rat bone marrow cells, obtained from the
      femora of Wistar rats, were precultured for 7 d in osteogenic medium. Then, the
      cells were harvested and seeded in 24-well plates at a concentration of 20,000
      cells/well. The wells were either precoated with 100 microg/ml EMD, or left
      uncoated. The seeded cells were cultured in osteogenic medium for 32 d and
      analysed for cell attachment (by using the Live and Dead assay), cell growth (by
      determining DNA content) and cell differentiation (by measuring alkaline
      phosphatase activity and calcium content, and by using scanning electron
      microscopy and the reverse transcription-polymerase chain reaction). RESULTS: The
      results showed that at the 4-h time point of the experiment, more cells were
      attached to EMD-negative wells, but this effect was no longer apparent at 24 h.
      DNA analysis revealed that both groups showed a similar linear trend of cell
      growth. No differences in alkaline phosphatase activity or calcium content were
      observed, and no differences in gene expression (osteocalcin, alkaline
      phosphatase and collagen type I) were found between the groups. CONCLUSION: Based
      on our results, we conclude that EMD had no significant effect on the cell growth
      and differentiation of rat bone marrow cells.

PMID- 16953825
TI  - Secretory leukocyte protease inhibitor and its potential interactions with
      elastase and cathepsin B in gingival crevicular fluid and saliva from patients
      with chronic periodontitis.
AB  - BACKGROUND AND OBJECTIVE: Elastase is carried into the oral cavity by gingival
      crevicular fluid (GCF) from periodontal lesions. Our study investigated the
      regulation of elastase activity by secretory leukocyte protease inhibitor (SLPI)
      and the possible action of another GCF protease on this protective salivary
      component. MATERIAL AND METHODS: Whole-mouth saliva (WMS), parotid saliva (PS)
      and GCF were obtained from 19 patients with periodontitis. The concentrations of
      active elastase and cathepsin B were determined using peptide substrates. SLPI
      and alpha1-proteinase inhibitor (alpha1PI) concentrations were determined using
      enzyme-linked immunosorbent assays (ELISAs). The molecular forms of SLPI were
      examined by immunoblotting. RESULTS: The molar concentrations of elastase,
      cathepsin B and alpha1PI were higher in GCF than in WMS and especially PS (p <
      0.0002). The GCF SLPI concentrations were also higher than the WMS SLPI
      concentrations (p < 0.05). All WMS components increased with GCF content,
      significantly for elastase and SLPI (p < 0.002). In GCF, the concentration of
      alpha1PI was higher than the concentration of SLPI (p < 0.0002), while there was
      no significant difference for WMS. SLPI and elastase levels in GCF and WMS were
      inversely related (p < 0.005). In SLPI immunoblots, PS contained only the intact
      14-kDa molecule of SLPI, while WMS also contained an 8-kDa fragment. For WMS
      there was a positive correlation between SLPI degradation and cathepsin B (p <
      0.002). Incubation of WMS alone or of PS with GCF in the presence of cysteine
      proteinase activators caused SLPI immunoreactivity to shift to 8 kDa. CONCLUSION:
      For GCF, serum-derived alpha1PI is the major elastase inhibitor, but in WMS SLPI
      probably reduces activity. The inflamed gingivae can be an additional source of
      SLPI in the oral cavity, but here the molecule is apparently cleaved by GCF
      cysteine proteinases, such as cathepsin B.

PMID- 16953826
TI  - Salivary matrix metalloproteinase-8 in patients with and without coronary heart
      disease may indicate an increased susceptibility to periodontal disease.
AB  - BACKGROUND AND OBJECTIVE: Tissue destruction caused by periodontitis may increase
      the number of cytokines implicated in the pathogenesis of cardiovascular
      diseases. We measured the concentration of the leukocyte-derived proteolytic
      enzyme, salivary neutrophil collagenase-2 [matrix metalloproteinase-8 (MMP-8)],
      as a marker of periodontal disease and assessed its relationship to coronary
      heart disease (CHD). Our aim was to study whether salivary MMP-8 levels were
      different among patients with and without CHD. The hypothesis was that patients
      with heart disease might present higher salivary MMP-8 levels than
      cardiologically healthy controls. MATERIAL AND METHODS: Saliva samples were taken
      from 256 patients with CHD and from 250 matched controls with known oral and
      general health status. The MMP-8 levels in saliva were analyzed by
      immunofluorometric assay, salivary albumin was assessed by enzyme-linked
      immunosorbent assay (ELISA) and total protein was determined using the
      colorimetric method. We further investigated the molecular forms and isoform
      distribution of salivary MMP-8 by western immunoblotting. The MMP-8 results were
      adjusted for the number of teeth and salivary protein concentrations. RESULTS:
      The adjusted logarithmic MMP-8 values were 0.145 +/- 0.245 microg/l in patients
      with CHD and 0.088 +/- 0.115 microg/l in controls (p < 0.01). The respective MMP
      8 : total protein and MMP-8 : albumin ratios were also significantly higher in
      CHD patients than in non-CHD subjects. CONCLUSION: Elevated salivary MMP-8 levels
      seemed to associate with CHD, suggesting more tissue breakdown as a result of
      periodontitis among the patients with heart disease.

PMID- 16953829
TI  - Apoptosis in liver disease.
AB  - The description of the morphological hallmarks of programmed cell death,
      apoptosis, in 1972 by Kerr, Wyllie and Currie started a field of research that
      revolutionized our understanding of cellular proliferation, tissue homeostasis
      and pathophysiology of many diseases. In the following years, a series of
      proteins involved in signaling and intracellular death pathways were identified
      and 30 years later the Noble Prize for physiology and medicine was awarded to S.
      Brenner, H. R. Horvitz and J. E. Sulston for their discoveries related to
      describing the mechanisms of cell death (apoptosis). The delineation of the
      signaling pathways that mediate apoptosis changed the paradigms of understanding
      in many liver diseases. The most detailed analyzed mode of apoptosis involves a
      cell surface-based receptor-ligand system. Death receptors are typically members
      of the tumor necrosis factor-receptor superfamily and comprise an intracellular
      death domain. Following ligand binding to the receptor, intracellular adapter
      molecules are recruited to the receptor and subsequently transmit the apoptotic
      signal. Intracellular organelle-dependent signaling occurs, and effector
      molecules then augment the receptor-initiated apoptosis process. Cell death and
      degradation follows the activation of a highly regulated set of cytosolic and
      nuclear proteases and DNAses. Receptor-independent activation of the apoptotic
      process can occur as part of the cytotoxicity related to UV radiation,
      chemotherapeuticals or other DNA-damaging agents through activation of
      intracellular sensors of cellular integrity, e.g. the tumor suppressor gene p53.
      In contrast to necrosis, apoptosis is not commonly accompanied by an inflammatory
      response that causes collateral cell damage. The apoptotic program is highly
      effective in eliciting cell death and thus must be tightly controlled. This is
      achieved through continuous integration of pro- and antiapoptotic signals at the
      individual cell level. Dysregulation of the apoptotic process, resulting in too
      much or too little cell death, has potentially devastating effects and has been
      implicated in many forms of liver disease like acute liver failure or
      hepatocellular carcinoma. This review will focus initially on recent progress in
      signaling events of hepatocellular apoptosis and subsequently discuss the
      consequences for the hepatic pathophysiology that involves disarrangement of
      hepatocellular apoptosis.

PMID- 16953830
TI  - Role of neutrophils in acute inflammatory liver injury.
AB  - Hepatic infiltration of polymorphonuclear leukocytes (neutrophils) is an early
      response to tissue injury, cellular stress or systemic inflammation. Neutrophil
      activation is vital for host-defense and the removal of cell debris but can also
      cause additional tissue damage or even liver failure. In order to prevent the
      detrimental effects of neutrophils without compromising host-defense reactions,
      it is important to understand the mechanisms of neutrophil hepatotoxicity. The
      first step in the pathophysiology is the priming and recruitment of neutrophils
      into the liver vasculature by inflammatory mediators, e.g. cytokines, chemokines,
      or complement factors. Most critical for parenchymal cell damage is the
      accumulation in sinusoids, which does not depend on cellular adhesion molecules.
      The next step is the extravasation into the parenchyma. This process requires a
      chemotactic signal from hepatocytes or already extravasated neutrophils and
      depends on cellular adhesion molecules on neutrophils (beta(2) or beta(1)
      integrins) and on endothelial cells (intercellular or vascular cell adhesion
      molecules). The third step is the direct contact with target cells (hepatocytes),
      which involves beta(2) integrins and triggers the full activation of the
      neutrophil with a long-lasting adherence-dependent oxidant stress and
      degranulation. The oxidants diffuse into hepatocytes and trigger an intracellular
      oxidant stress, mitochondrial dysfunction and eventually cause oncotic necrotic
      cell death. Neutrophil-derived proteases facilitate extravasation and are
      involved in the regulation of inflammatory mediator production. Based on these
      mechanisms, it appears that strengthening of the intracellular defense mechanisms
      in hepatocytes may be the most promising therapeutic approach to selectively
      prevent neutrophil-mediated tissue damage without compromising their host-defense
      function.

PMID- 16953831
TI  - Comparison of (11)C-acetate positron emission tomography and (67)Gallium citrate
      scintigraphy in patients with hepatocellular carcinoma.
AB  - AIMS: Nuclear imaging may have an increasing role in the diagnosis of
      hepatocellular carcinoma (HCC). The aim of this study was to compare
      prospectively the Gallium-67 citrate ((67)Ga) scintigraphy results with those
      obtained by positron emission tomography (PET) using (11)C-acetate in patients
      with HCC. METHODS: We prospectively analysed 21 patients (mean age, 64+/-11
      years) with histopathologically verified HCC undergoing (11)C-acetate PET and
      (67)Ga scintigraphy. (67)Ga scans were not performed in three of these 21
      patients due to the exacerbation of the disease. Whole-body (11)C-acetate PET
      were performed following intravenous injection of 850 MBq of (11)C-acetate. For
      (67)Ga scintigraphy, whole-body, planar and single photon emission computed
      tomography imaging acquisitions were performed after intravenous application of a
      mean dose of 189 MBq (67)Ga. RESULTS: (67)Ga scintigraphy found abnormalities
      only in 10 of 18 patients (56%) and detected 22 of 46 clinically involved sites
      (48%); it was false-positive in two patients. (11)C-acetate PET found
      abnormalities in 14 of 18 patients (78%) and detected 36 of 46 clinical lesions
      (78%); it was false-positive in one patients. In one patient with left
      supraclavicular lymph node metastases, neither the (67)Ga scintigraphy nor the
      conventional computed tomography have shown the lesions, which were clearly
      demonstrated by the (11)C-acetate PET. CONCLUSION: Our results indicate
      significantly higher sensitivity and specificity of (11)C-acetate PET than (67)Ga
      scan in detection of HCC lesions. This study suggests that imaging with (11)C
      acetate PET might play a potential role in the diagnostic workup of patients with
      HCC.

PMID- 16953832
TI  - Small hepatic nodules (< or =2 cm) in cirrhosis patients: characterization with
      contrast-enhanced ultrasonography.
AB  - AIM: We evaluated the efficacy of contrast-enhanced ultrasonography (CEUS) for
      the characterization of small hepatic nodules (< or =2 cm) in cirrhosis patients.
      PATIENTS AND METHODS: Thirty cirrhosis patients with 30 hepatic nodules (1-2 cm)
      were enrolled in this study. Eighteen hepatic nodules were hepatocellular
      carcinomas (HCC) and 12 were benign lesions. CEUS was performed using microbubble
      contrast (Levovist). With surrounding hepatic parenchyma as a reference, two
      characteristics of hepatic nodules, including arterial phase enhancement (AE) and
      the absence of delayed phase enhancement (ADE), were evaluated as criteria for
      the diagnosis of HCC. A radiologist independently reviewed the dynamic computed
      tomographies (CT) of 26 hepatic nodules. RESULTS: CEUS showed AE in 15 nodules
      (13 HCC and two benign) and ADE in 17 lesions (14 HCC and three benign). For HCC,
      the coincidental AE of both CEUS and dynamic CT was 40%. Using both AE and ADE
      for HCC diagnosis, the sensitivity, specificity, accuracy, positive predictive
      value and negative predictive values were 55.6%, 91.7%, 70%, 90.9% and 57.9%,
      respectively. When using either AE or ADE for HCC diagnosis, the same parameters
      were 94.4%, 66.7%, 83.3%, 81% and 88.9%, respectively. One benign hepatic nodule
      with both AE and ADE was diagnosed as HCC 29 months after the CEUS study.
      CONCLUSIONS: A combination of characteristics of AE and ADE as determined by CEUS
      was highly specific for small HCCs in cirrhosis patients. Concurrent delayed
      phase imaging is useful in the diagnosis of small hypovascular HCCs.

PMID- 16953834
TI  - Rifampin is safe for treatment of pruritus due to chronic cholestasis: a meta
      analysis of prospective randomized-controlled trials.
AB  - OBJECTIVES: To determine the safety and efficacy of rifampin for treatment of
      pruritus associated with cholestasis due to chronic liver disease. METHODS:
      Medical literature was searched systematically using keywords as rifampicin,
      rifampin, rifamycin, cholestasis, pruritus, itching, and liver disease. Trials
      that compared the efficacy of rifampin with placebo/alternative for treatment of
      pruritus due to chronic cholestasis were selected for analysis. Primary outcomes
      were resolution of pruritus and development of side effects. Association was
      measured with the odds ratio (OR). Breslow-Day method was used to treat for
      homogeneity under null hypothesis that OR was consistent across all the trials.
      Corrected Mantel-Haenszel chi(2) test was used to test if OR differed
      systematically from value of 1. RESULTS: Five prospective randomized-controlled
      cross-over trials with 61 patients were identified. Treatment with rifampin led
      to complete or partial resolution of pruritus in 47 (77%) patients as compared
      with 12(20%) treated with placebo or alternative (OR 15.2, 95% confidence
      interval 5.2-45.6, P=0.001). Four (7%) patients treated with rifampin suffered
      side effects, which resolved after its discontinuation. There was no incidence of
      hepatotoxicity. Test of heterogeneity for primary end points among the trials was
      not significant (P=0.16). CONCLUSION: This meta-analysis suggests that rifampin
      is safe and effective for treatment of pruritus due to chronic cholestasis. This
      analysis also suggests that use of rifampin for short duration is associated with
      a low risk of hepatotoxicity.

PMID- 16953833
TI  - Endotoxin tolerance in human intrahepatic biliary epithelial cells is induced by
      upregulation of IRAK-M.
AB  - BACKGROUND/AIM: Biliary epithelial cells possess an innate immune system
      consisting of Toll-like receptors (TLRs). Although the human bile contains
      lipopolysaccharide (LPS) in normal as well as diseased livers, LPS
      physiologically does not elicit an inflammatory response in the biliary tree.
      This absence of a response to LPS could be due to the 'endotoxin tolerance'
      speculated to maintain innate immune homeostasis in organs. Our aim here is to
      clarify the presence and molecular mechanisms of endotoxin tolerance of biliary
      epithelium. METHODS AND RESULTS: In nuclear factor-kappaB (NF-kappaB)-DNA binding
      assays using three-cultured human intrahepatic biliary epithelial cell (HIBEC)
      lines, all the cells responded to LPS (TLR4 ligand) by activating NF-kappaB, but
      pretreatment with LPS for 24 h effectively induced tolerance against any
      subsequent stimulation with LPS (endotoxin tolerance). This tolerance was also
      induced by pretreatment with Pam(3)Cys-Ser-(Lys)(4) trihydrochloride
      (Pam(3)CKS(4), TLR1/2 ligand). Then, real-time polymerase chain treaction and
      Western blotting revealed that LPS treatment upregulated the expression of IRAK-M
      (a negative regulator of TLR signaling), but did not affect interleukin-1
      receptor-associated kinase-1 (IRAK-1, an essential molecule of TLR signaling), in
      HIBECs. Moreover, immunohistochemistry revealed that IRAK-M was diffusely
      expressed in intrahepatic bile ducts. CONCLUSIONS: This study showed that the
      mechanism of endotoxin tolerance exists in the intrahepatic biliary tree and is
      possibly induced by the expression of IRAK-M in the intrahepatic biliary
      epithelium, suggesting that the endotoxin tolerance is important in maintaining
      innate immune biliary homeostasis.

PMID- 16953835
TI  - Viral factors correlate with hepatitis B e antigen seroconverson in patients with
      chronic hepatitis B.
AB  - BACKGROUND/AIMS: Seroconversion (SC) from hepatitis B envelope antigen (HBeAg) to
      anti-HBe usually indicates lower viral loads, resolved hepatitis activity and
      improved long-term outcomes. However, the role of viral factors in the
      development of SC remains largely unknown. We thus comprehensively studied these
      factors in 25 patients with sustained HBeAg SC and seven control patients with
      sustained loss of HBeAg. METHODS: We determined viral factors in serum samples
      obtained 1 year before, 6 months before, 3 months before, at the time of, 6
      months after and 1 year after HBeAg SC or HBeAg loss. Precore A1896 and basal
      core promoter T1762/A1764 mutants were determined by polymerase chain reaction
      (PCR)-based assays. Serum HBV levels were determined by a real-time PCR assay.
      RESULTS: We found that decline of serum viral load, frequently accompanied by
      hepatitis exacerbation, occurred within 1 year before HBeAg SC. The proportions
      of precore and BCP mutations also increased gradually throughout the process of
      HBeAg SC. The virologic features were similar between HBeAg SC group and HBeAg
      loss group. Before HBeAg SC or loss, genotype B patients had higher serum viral
      loads and lower proportions of BCP mutation compared with genotype C patients.
      CONCLUSION: Our findings suggested that viral factors correlate with the
      development of sustained HBeAg SC or loss.

PMID- 16953836
TI  - Useful parameters for distinguishing nonalcoholic steatohepatitis with mild
      steatosis from cryptogenic chronic hepatitis in the Japanese population.
AB  - BACKGROUND/AIMS: As detecting mild steatosis is difficult by abdominal
      ultrasonography (US), nonalcoholic steatohepatitis (NASH) with mild steatosis may
      sometimes be confused with cryptogenic chronic hepatitis. We aimed to test this
      possibility and to isolate factors that may indicate NASH. METHODS: First, 53
      Japanese patients diagnosed as having cryptogenic chronic hepatitis by laboratory
      examination and US were enrolled. These patients were histologically divided into
      NASH and non-NASH groups, and their clinical features were compared. Second, the
      diagnostic accuracy of predictors of NASH was examined prospectively. RESULTS:
      Fifteen patients (28%) were histologically diagnosed as having NASH with mild
      steatosis. Multivariable analysis revealed that body mass index (BMI) and serum
      ferritin level were independent predictors of NASH. The best cutoff values to
      detect NASH were assessed by using receiver-operating characteristic curves:
      BMI>25.2 kg/m(2) and serum ferritin level >142 ng/ml. When both markers were
      concomitantly negative, the negative predictive value to detect NASH was 100%.
      CONCLUSIONS: In cases of mild steatosis, US is not a perfect tool for the
      accurate diagnosis of NASH. BMI and serum ferritin level are useful
      discriminators of NASH from cryptogenic chronic hepatitis, and might be helpful
      markers for diagnosing NASH more accurately in Japanese patients.

PMID- 16953837
TI  - Growth inhibitory effects of pegylated IFN alpha-2b on human liver cancer cells
      in vitro and in vivo.
AB  - PURPOSE: We investigated the effects of pegylated IFN-alpha2b (PEG-IFN-alpha2b)
      on the growth of human liver cancer cells. METHODS: The effect of PEG-IFN-alpha2b
      on the proliferation of 13 liver cancer cell lines was investigated in vitro.
      Chronological changes in growth and IFN-alpha receptor-2 (IFNAR-2) expression
      were monitored in hepatocellular carcinoma (HCC) cells (HAK-1B) cultured with PEG
      IFN-alpha2b. After HAK-1B cells were transplanted into nude mice, various doses
      of PEG-IFN-alpha2b or IFN-alpha2b were administered, and tumor volume, weight,
      histology, and IFNAR-2 expression were examined. RESULTS: PEG-IFN-alpha2b
      inhibited the growth of nine cell lines with apoptosis in a dose- and time
      dependent manner. Continuous contact with PEG-IFN-alpha2b induced time-dependent
      growth inhibition and down-regulation of IFNAR-2 expression. PEG-IFN-alpha2b
      induced a dose-dependent decrease in tumor volume and weight, a significant
      increase of apoptotic cells, and a decrease in IFNAR-2 expression in the tumor.
      The clinical dose for chronic hepatitis C was also effective. The antitumor
      effect of PEG-IFN-alpha2b was significantly stronger than that of non-PEG-IFN
      alpha2b in vivo. CONCLUSIONS: Continuous contact with PEG-IFN-alpha2b induces
      strong antitumor effects and the down-regulation of IFNAR-2 in HCC cells. The
      data suggest potential clinical application of PEG-IFN-alpha2b for the prevention
      and treatment of HCC.

PMID- 16953838
TI  - Expression of iron regulatory genes in a rat model of hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: The altered iron metabolism in hepatocellular carcinomas (HCCs),
      characterized by the iron-deficient phenotype, is suggested to be of importance
      for tumour growth. However, the underlying molecular mechanisms remain poorly
      understood. We asked whether these iron perturbations would involve altered
      expression of genes controlling iron homeostasis. METHODS: HCCs were induced in
      rats by the Solt and Farber protocol of chemical hepatocarcinogenesis, and to
      evaluate the effects of iron loading, one group of animals were supplemented with
      dietary iron during tumour progression. Tissue iron contents were determined,
      labelling indices of S-phase nuclei were calculated, and mRNA levels of iron
      regulatory genes were quantitated. Protein levels of ferroportin1 were determined
      with Western blot. RESULTS: HCCs displayed reduced amount of tissue iron and lack
      of histologically stainable iron. HCCs expressed significantly higher mRNA levels
      of genes involved in iron uptake (transferrin receptor-1, divalent metal ion
      transporter-1), ferroxidase activity (Ferritin-H), and iron extrusion
      (ferroportin1). The protein levels of ferroportin1 in iron-deficient HCCs were
      similar as in control livers, and did not increase in HCCs exposed to iron.
      Hepcidin mRNA levels were decreased in iron-deficient HCCs, rose in response to
      iron loading and correlated to the tissue iron content. CONCLUSIONS: Taken
      together, the altered expressions of iron-regulatory genes in HCCs possibly
      reflect an increased demand for bioavailable iron and a high iron turnover in
      neoplastic cells.

PMID- 16953839
TI  - IFNgamma expression inhibits LHBs storage disease and ground glass hepatocyte
      appearance, but exacerbates inflammation and apoptosis in HBV surface protein
      accumulating transgenic livers.
AB  - BACKGROUND/AIMS: Interferon gamma (IFNgamma) controls hepatitis B virus
      replication. As systemic application may cause severe adverse effects, approaches
      of liver-directed IFNgamma gene therapy may represent an attractive alternative
      for treatment of chronic viral hepatitis B and thus needs testing in vivo in
      suitable animal models. METHODS: We therefore crossbred Alb-1HBV transgenic mice
      overexpressing the large HBV surface protein (LHBs) in their livers and
      developing LHBs storage disease and ground glass hepatocyte appearance with SAP
      IFNgamma transgenic animals previously shown to exhibit constitutive hepatic
      IFNgamma expression, and analyzed the resulting double-transgenic offspring.
      RESULTS: We found that IFNgamma coexpression significantly reduced hepatic LHBs
      expression and thereby inhibited hepatocellular LHBs storage disease and ground
      glass hepatocyte appearance. The beneficial antiviral IFNgamma effects as
      observed in Alb1-HBV SAP-IFNgamma double-transgenic livers were associated with
      significantly elevated serum ALT concentrations, massive mononuclear cell
      infiltrates, appearance of Councilman bodies, and increased alpha-PARP (poly(ADP
      ribose) polymerase cleavage). CONCLUSIONS: Exacerbation of hepatic
      necroinflammation and increased hepatocellular apoptosis rate in IFNgamma
      expressing Alb1-HBV transgenic livers suggest that special precautions be taken
      for testing approaches of liver-specific IFNgamma expression in patients with
      chronic hepatitis B.

PMID- 16953840
TI  - Ischemic preconditioning improves liver regeneration by sustaining energy
      metabolism after partial hepatectomy under ischemia in rats.
AB  - BACKGROUND: The protective effect of ischemic preconditioning (IPC) has been
      reported on improvement of survival, reduction of liver necrosis and enhancement
      of the regenerative capacity of hepatocytes after partial hepatectomy. This study
      was undertaken to confirm that IPC has a significant impact on regeneration of
      hepatocytes after partial hepatectomy in ischemically damaged liver. In addition,
      we sought to examine the role of adenine nucleotides in this process. METHODS:
      Wistar rats were subjected to 60 min of total hepatic ischemia, followed by 70%
      hepatectomy. The animals were subdivided into an IPC (10/15 min) group and a non
      IPC (control) group. Liver function tests and arginase activity were analyzed.
      Hepatic adenosine triphosphate (ATP), adenosine diphosphate and adenosine
      monophosphate were measured using gradient high-performance liquid
      chromatography. The liver regeneration was identified using relative liver weight
      and proliferating cell nuclear antigen (PCNA) labeling index. RESULTS: IPC
      treatment improved serum liver enzymes and tissue arginase activity (P<0.05) when
      compared with the control group. The preconditioned livers were associated with
      upregulation of ATP expression and also increased tissue energy charge.
      Regenerated liver weight in the IPC group was significantly higher than in the
      control group (P<0.05). The PCNA labeling index in the remnant livers in the IPC
      group was also significantly increased at 24 and 48 h after partial hepatectomy
      (P<0.05). CONCLUSION: These results suggest that IPC-augmented liver regeneration
      after hepatectomy, probably due to the stabilization of energy metabolism in
      rats.

PMID- 16953841
TI  - Quantitative trait loci analysis of mice administered the methionine-choline
      deficient dietary model of experimental steatohepatitis.
AB  - BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a common disease with a poorly
      understood etiology, and the methionine-choline-deficient (MCD) diet is a
      nutritional model of NASH. Quantitative trait loci (QTL) analysis is a standard
      method for chromosomal mapping of polygenic disease traits. The purpose of this
      study is to administer mice an MCD diet in order to determine the strain-specific
      susceptibility for developing steatohepatitis, and to apply a computational
      methodology of QTL analysis to identify associated chromosomal susceptibility
      loci. METHODS: Inbred mice were fed an MCD diet and alanine aminotransferase
      (ALT), hepatic triglycerides, liver weight, and weight loss were measured as
      phenotypic markers of steatohepatitis. RESULTS: A/J mice developed the highest
      ALT and hepatic triglyceride levels. Using linear regression analysis, gene loci
      affecting serum ALT levels were identified on four chromosomes, and four loci
      that affect liver weight were also identified. In contrast, no QTLs for hepatic
      triglycerides or body weight were identified. Of note, loci for ALT and liver
      weight co-localized to proximal segments of chromosomes 2 and 15, in regions
      previously identified as QTLs for liver fibrosis. CONCLUSIONS: These data
      indicate that experimental steatohepatitis is a polygenic disease with genes
      determining ALT, liver weight, and liver fibrosis.

PMID- 16953842
TI  - Prevention of hepatic fibrosis in nonobese diabetic mice: a critical role for
      interferon-gamma.
AB  - BACKGROUND/AIMS: Nonobese diabetic (NOD) mice, a model of type I diabetes
      mellitus, harbor certain unique defects in their immune system. The aim of this
      study was to investigate how NOD mice show hepatic injury and subsequent
      fibrogenic responses. METHODS: Hepatic fibrosis was induced by intraperitoneal
      injections of dimethylnitrosamine (DMN), and assessed biochemically and
      histologically. Expressions of cytokine messenger RNA (mRNA) in the liver were
      determined. RESULTS: In a model of liver cirrhosis induced by dimethylnitrosamine
      (DMN), we found that NOD mice had lower levels of hepatic fibrosis and better
      survival than control ICR mice. The resistance to DMN-induced lethality in NOD
      mice was independent of apoptosis and necrosis of hepatocytes, but apparently due
      to the prevention of hepatic fibrosis. We also found increased inductions of
      interferon-gamma (IFN-gamma) mRNA in the liver of NOD mice and of intracellular
      IFN-gamma from intrahepatic T cells following DMN administration. Treatment with
      neutralizing anti-IFN-gamma-antibody cancelled the inhibition of hepatic fibrosis
      in NOD mice. CONCLUSIONS: These results suggest that IFN-gamma is effective for
      inhibiting hepatic fibrosis and that genetic host factors may be important in
      determining differential responses to injury.

PMID- 16953843
TI  - Incretin mimetics as a novel therapeutic option for hepatic steatosis.
AB  - BACKGROUND: Fat accumulation in the liver or non-alcoholic fatty liver disease
      (NAFLD) is regarded as a key pathogenic factor and component of the metabolic
      syndrome. It was reported that administration of the incretin mimetic exenatide
      reversed hepatic steatosis in an obese mouse model. We had the opportunity to
      study the effect of additional exenatide administration on liver fat content in a
      patient with type 2 diabetes. CASE REPORT: A 59-year-old male with poorly
      controlled type 2 diabetes was treated with exenatide in addition to metformin
      monotherapy. Following 44 weeks of exenatide therapy, mean the liver fat measured
      by liver spectroscopy declined from 15.8% to 4.3%. This dramatic decrease in
      liver fat was accompanied by significant beneficial changes in several
      cardiovascular disease risk factors and improvement of all liver enzymes, in
      particular alanine aminotransferase, the most important marker of liver
      steatosis. CONCLUSION: This case report suggests that the incretin mimetic
      exenatide decreases hepatic fat accumulation and may play a role in the future
      treatment of NAFLD, and the associated insulin resistance and cardiovascular risk
      factors in an ever-growing high-risk population.

PMID- 16953844
TI  - Cytoplasmic p21(WAF1/CIP1) expression in human hepatocellular carcinomas.

PMID- 16953845
TI  - Abstracts of the 45th Annual Scientific Meeting of the British Society for
      Clinical Cytology. Edinburgh, Scotland, United Kingdom. September 10-13, 2006.

PMID- 16953847
TI  - Down syndrome screening in Australia: more luck than choice.

PMID- 16953848
TI  - Radical trachelectomy.
AB  - This review examines the emerging place of radical trachelectomy in the
      management of women with cervical cancer who are seeking fertility preservation.

PMID- 16953849
TI  - Is colposcopy needed following laser ablation for dysplasia?
AB  - AIMS: To evaluate the effectiveness of cytology and colposcopy in the follow up
      of women treated by laser CO(2) ablation for cervical intraepithelial neoplasia
      (CIN). METHODS: A retrospective analysis of 1784 patients with CIN treated with
      laser CO(2) ablation from 1998 to 2003 at the Royal Women's Hospital, Melbourne.
      Data were collected prospectively in a computerised colposcopy database utilised
      in the Dysplasia Unit. RESULTS: There was equal distribution in the study
      population treated for low-grade intraepithelial neoplasia (LSIL) and high-grade
      intraepithelial neoplasia (HSIL), with no significant age difference in both
      groups (mean 27.6 years). The success rate of treatment of LSIL (94%) was similar
      to that of HSIL (92%). Fifty-seven per cent of all failures occurred within the
      first year of treatment. Colposcopy was more sensitive in detecting
      intraepithelial neoplasia (SIL) than cytology, whereas cytology was more
      specific. No case of cancer was diagnosed on follow up. CONCLUSIONS: CO(2) laser
      ablation was equally effective in treating different grades of CIN. There is a
      continuing incidence of recurrent CIN, even up to five years after initial
      treatment, which suggests that it is necessary for patients to adhere to long
      term follow up. The combination of cytology and colposcopic assessment is
      essential for surveillance of SIL in the initial two years after treatment.

PMID- 16953850
TI  - What do obstetricians think about media influences on their patients?
AB  - BACKGROUND: Patients are playing an increasingly active role in decision-making
      about their care and are becoming increasingly informed about their health.
      Traditionally, sources of information about pregnancy and birth were family and
      friends and, in more recent times, antenatal classes. Evidence suggests that the
      media, particularly the Internet, is an increasingly influential source of
      information about illness and health. AIMS: The aim of this study was to survey
      Australian Fellows of the Royal Australian and New Zealand College of
      Obstetricians and Gynaecologists (RANZCOG) about their perceptions of sources of
      patient information about pregnancy and birth, particularly the media and the
      Internet. METHODS: A two-page survey with a reply paid envelope was sent to all
      Australian Fellows of RANZCOG. Most questions only allowed a selection of
      prespecified categorical options. Some questions allowed open-ended replies that
      were assessed using thematic analysis. RESULTS: RANZCOG fellows thought that
      family and friends were the most important source of information for patients
      about pregnancy and birth followed by formal antenatal education, although they
      ranked the influence of the Internet above that of free-to-air television.
      Responses suggested that women in both the public and the private sectors were
      accessing the Internet. CONCLUSIONS: Fellows felt that their patients are
      actively involved in decisions about their care during pregnancy and birth and
      that the media influences their knowledge and attitudes. The Internet appears to
      have an increasingly important role in providing women with information.
      Obstetricians need to be aware of what their patients are accessing on the
      Internet.

PMID- 16953851
TI  - Extremely skewed X-chromosome inactivation patterns in women with recurrent
      spontaneous abortion.
AB  - BACKGROUND: The role of extremely skewed X-chromosome inactivation (XCI) has been
      questioned in the pathogenesis of recurrent spontaneous abortion (RSA) but the
      results obtained were conflicting. AIMS: We therefore investigated the XCI
      patterns in peripheral blood DNA obtained from 80 patients who had RSA and 160
      age-matched controls. METHODS: Pregnancy history, age, karyotype, and disease
      information was collected from all subjects. The methylation status of a highly
      polymorphic cytosine-adenine-guanine repeat in the androgen-receptor (AR) gene
      was determined by use of methylation-sensitive restriction enzyme HpaII and
      polymerase chain reaction. RESULTS: Skewed XCI (> 85% skewing) was observed in 13
      of the 62 patients informative for the AR polymorphism (20.9%), and eight of the
      124 informative controls (6.4%) (P = 0.0069; chi2 test). More importantly,
      extremely skewed XCI, defined as > 90% inactivation of one allele, was present in
      11 (17.7%) patients, and in only two controls (P = 0.0002; chi2 test).
      CONCLUSIONS: These results support the interpretation that disturbances in XCI
      mosaicism may be involved in the pathogenesis of RSA.

PMID- 16953852
TI  - Customised birthweight: coefficients for an Australian population and validation
      of the model.
AB  - BACKGROUND: Published birthweight references in Australia do not fully take into
      account constitutional factors that influence birthweight and therefore may not
      provide an accurate reference to identify the infant with abnormal growth.
      Furthermore, studies in other regions that have derived adjusted (customised)
      birthweight references have applied untested assumptions in the statistical
      modelling. AIMS: To validate the customised birthweight model and to produce a
      reference set of coefficients for estimating a customised birthweight that may be
      useful for maternity care in Australia and for future research. METHODS: De
      identified data were extracted from the clinical database for all births at the
      Mater Mother's Hospital, Brisbane, Australia, between January 1997 and June 2005.
      Births with missing data for the variables under study were excluded. In addition
      the following were excluded: multiple pregnancies, births less than 37 completed
      week's gestation, stillbirths, and major congenital abnormalities. Multivariate
      analysis was undertaken. A double cross-validation procedure was used to validate
      the model. RESULTS: The study of 42,206 births demonstrated that, for statistical
      purposes, birthweight is normally distributed. Coefficients for the derivation of
      customised birthweight in an Australian population were developed and the
      statistical model is demonstrably robust. CONCLUSIONS: This study provides
      empirical data as to the robustness of the model to determine customised
      birthweight. Further research is required to define where normal physiology ends
      and pathology begins, and which segments of the population should be included in
      the construction of a customised birthweight standard.

PMID- 16953853
TI  - Intrapartum analgesia and its association with post-partum back pain and headache
      in nulliparous women.
AB  - BACKGROUND: The effect of intrapartum analgesia on post-partum maternal back and
      neck pain, headache and migraine, is uncertain. AIMS: To determine if nulliparous
      women having epidural analgesia during labour have a similar incidence of the
      above-mentioned post-partum symptoms compared with women managed using other
      forms of pain relief. METHODS: Secondary analysis of cohort data from a
      randomised trial in which nulliparous women intending to deliver vaginally were
      randomised to either epidural analgesia (EPI) or continuous midwifery support
      (CMS) at admission for delivery. Because of high cross-over rates, groups were
      initially defined by the randomised treatment allocation and the actual treatment
      received (CMS-CMS n = 185, EPI-CMS n = 117, EPI-EPI n = 376 and CMS-EPI n = 314).
      Univariate analysis showed no difference between groups, so final analysis was
      based on the actual treatment received. RESULTS: Six hundred and ninety women
      received epidural analgesia (EPIDURAL) and 302 received other methods of pain
      relief including CMS. Back pain was common before, during and after pregnancy,
      and risk factors for post-partum back pain at six months were back pain prior to
      pregnancy or at two months post-partum. Epidural analgesia, mode of delivery,
      spontaneous or induced labour, birthweight and back pain during pregnancy had no
      significant relationship with post-partum back pain at six months. Headache was
      significantly more common in the EPIDURAL group during pregnancy and at two
      months post-partum, but not at six months. Migraine was not associated with
      intrapartum analgesia. CONCLUSIONS: This analysis supports previous research
      suggesting that epidural analgesia is not a significant risk factor for
      persisting post-partum back pain, headache or migraine.

PMID- 16953854
TI  - The association between intratwin birthweight discordance and preterm birth in
      twin pregnancy.
AB  - BACKGROUND: Previous studies found that increased birthweight discordance among
      twins was associated with increased risk of perinatal mortality and morbidity,
      but there is disagreement regarding the relationship between birthweight
      discordance and the risk of preterm birth. AIMS: To examine the relationship
      between intratwin birthweight discordance and preterm birth, and the influence of
      total birthweight as a confounding factor. METHODS: We conducted a historical
      cohort study to assess the relationship between intratwin birthweight discordance
      and preterm birth, using the 1995-1997 twin registry data of the USA. Parallel
      analyses with and without adjustment for total birthweight were performed.
      RESULTS: A total of 147,262 eligible twin sets were included in the analysis. In
      the non-stratified analysis, preterm birth (< 37 weeks) rates were 64.3 and
      51.8%, respectively, in subjects with a birthweight discordance > 25% and in
      those < or = 25%. In the analysis stratified by total birthweight, the rates of
      preterm birth were higher in subjects with a birthweight discordance > 25% than
      in those < or = 25% at every total birthweight stratum. Changing the thresholds
      to define preterm birth or treating gestational age as a continuously distributed
      variable yielded similar results. Using other methods to adjust for total
      birthweight also reversed the direction of this relationship. CONCLUSIONS:
      Increased intratwin birthweight discordance is associated with increased risk of
      preterm birth, and adjustment for total birthweight biases the relationship to
      the wrong direction. Clinicians should be aware of the possibility of a preterm
      birth when there are signs of discordance in birthweight between the two twins.

PMID- 16953855
TI  - Pregnancy outcome in women presenting with pre-eclampsia at less than 25 weeks
      gestation.
AB  - OBJECTIVE: We aimed to (i) assess maternal and perinatal outcomes in pre
      eclampsia at < 25(0) weeks; and (ii) determine if any antenatal factors were
      associated with adverse maternal and perinatal outcomes. DESIGN: A retrospective
      study. SETTING: Tertiary referral hospital, Auckland, New Zealand. METHODS: Data
      were extracted from the clinical record and hospital database. The study
      population involved women admitted with pre-eclampsia at < 25(0) weeks, with a
      live singleton pregnancy, from 1997 to 2004 and managed expectantly. OUTCOME
      MEASURES: Maternal morbidity, perinatal death, neurodevelopmental outcome at 18
      months, small for gestational age assessed by population and customised
      birthweight centiles. RESULTS: Gestation at admission was the only antenatal
      variable associated with adverse perinatal outcome. Of 14 women admitted < 23
      weeks, no babies survived, but eight (62%) babies of women admitted in the 24th
      week (24(0)-24(6)) survived. Neurodevelopmental outcome was assessed in eight of
      nine survivors; two (25%) had moderate and two (25%) had minor disability. All
      babies in this cohort had birthweights < 5th customised centile. Only one baby
      (10%) weighing < 500 g survived. CONCLUSION: Maternal morbidity was high in this
      expectantly managed cohort. As no babies survived when pre-eclampsia occurred
      before 23 weeks, induction of labour should be considered. In the 24th week two
      thirds of babies survived and 25% had moderate handicap. This information may
      help clinicians and women in the future to make informed choices about
      management.

PMID- 16953856
TI  - The quality and size of yolk sac in early pregnancy loss.
AB  - BACKGROUND: Accurate differentiation between normal pregnancy and pregnancy loss
      in early gestation remains a clinical challenge. AIMS: To determine whether
      ultrasound findings of yolk sac size and morphology are valuable in relation to
      pregnancy loss at six to ten weeks gestation. METHODS: Transvaginal
      ultrasonography was performed in 111 normal singleton pregnancies, 25 anembryonic
      gestations, and 18 missed abortions. Mean diameters of gestational sac and yolk
      sac were measured. The relationship between yolk sacs and gestational sacs in
      normal pregnancies was depicted. The yolk sacs ultrasound findings in cases of
      pregnancy loss were recorded. RESULTS: In normal pregnancies with embryonic
      heartbeats, a deformed or an absent yolk sac was never detected. Sequential
      appearance of yolk sac, embryonic heartbeats and amniotic membrane was essential
      for normal pregnancy. The largest yolk sac in viable pregnancies was 8.1 mm.
      Findings in anembryonic gestations included an absent yolk sac, an irregular
      shaped yolk sac and a relatively large yolk sac (> 95% upper confidence limits,
      in 11 cases). In cases of missed abortion with prior existing embryonic
      heartbeats, abnormal findings included a relatively large, a progressively
      regressing, a relatively small, and a deformed yolk sac (an irregular-shaped yolk
      sac, an echogenic spot, or a band). CONCLUSION: A very large yolk sac may exist
      in normal pregnancy. When embryonic heartbeats exist, the poor quality and early
      regression of a yolk sac are more specific than the large size of a yolk sac in
      predicting pregnancy loss. When an embryo is undetectable, a relatively large
      yolk sac, even of normal shape, may be an indicator of miscarriage.

PMID- 16953857
TI  - Postnatal home visiting for illicit drug-using mothers and their infants: a
      randomised controlled trial.
AB  - BACKGROUND: Postnatal home-visiting programs for illicit drug-using mothers have
      reported some success in reducing harms in some areas but there is a lack of data
      on their impact on breastfeeding and immunisation rates. AIMS: To investigate the
      effect on breastfeeding, immunisation and parental drug use. The hypothesis was
      that the outcomes of the home-visiting group (HVG) would be superior to the
      control group (CG). METHOD: One hundred and fifty-two illicit drug-using women
      were recruited at 35-40 weeks gestation from King Edward Memorial Hospital,
      Perth, Western Australia and randomised after delivery to the HVG or the CG. The
      HVG had eight home visits; the CG had telephone contact at two months and a home
      visit at six months. The HVG received education and support for parenting,
      breastfeeding and child development. This was not provided by the research
      midwives for the CG. RESULTS: The main drugs were heroin, amphetamines, cannabis
      and benzodiazepines. Immunisation rates were similar for each group. Median
      duration of breastfeeding for the HVG was eight weeks (95% CI, 3.8-12.2); for the
      CG ten weeks (95% CI, 7.3-12.7). Drug use was reduced during pregnancy but
      increased by six months post-partum in both groups. The retention rates were: HVG
      93%; CG 86%. CONCLUSION: The hypothesis for this study was not supported. Long
      term studies are urgently required to assess the effects of parental drug use on
      infant and child development.

PMID- 16953858
TI  - Regional variations in prenatal screening across Australia: stepping towards a
      national policy framework.
AB  - BACKGROUND: A relatively few centres across Australia provide screening tests for
      maternal serum markers or ultrasound measurement of fetal nuchal translucency to
      assess risk of fetal anomalies such as Down syndrome. While providers engage in
      external accreditation and quality assurance programs, state and federal
      governments have been slow to formulate relevant policies and standards. AIM: In
      this paper we review the current practices across Australian states and
      territories and propose recommendations for developing a national policy
      framework. METHODS: Data on the number and types of screening tests provided as
      well as state policies, where they are available, were obtained from government
      reports and supplemented by a mail survey to selected stakeholders in each state
      or territory. RESULTS: At a jurisdictional level, our results highlight the need
      to integrate the collection and monitoring of antenatal population-screening
      programs to assess clinical effectiveness and program performance (detection and
      screen-positive rates, uptake of diagnostic tests as a result of screening).
      Women's expectations and satisfaction with the information they are provided
      should be evaluated and used to adjust education resources. At a local level,
      collaboration between providers of the separate tests, both public and private,
      would enable the ascertainment of outcomes of integrated screening programs. To
      complete the cycle, these data should inform decisions to improve antenatal
      screening programs at a national level. CONCLUSIONS: A primary goal at a national
      level would be to develop a consensus on key performance indicators for programs
      that clarify best practice guidelines and establish optimal performance and
      accreditation standards.

PMID- 16953859
TI  - Are pregnant Australian women well informed about prenatal genetic screening? A
      systematic investigation using the Multidimensional Measure of Informed Choice.
AB  - BACKGROUND: Ethical practice requires that decisions to participate in medical
      care be well informed. Investigations into prenatal genetic screening for Down
      syndrome have assessed women's knowledge but have not examined whether being well
      informed about the potential consequences of screening, such as subsequent
      diagnostic testing, diagnosis and termination, is associated with psychological
      distress for women. AIMS: To assess informed choice to participate in second
      trimester maternal serum screening (2MSS) in pregnant women using a validated
      measure and to compare anxiety levels in women who were well informed versus
      poorly informed. METHODS: A prospective cohort study where pregnant women
      completed the Multidimensional Measure of Informed Choice and the Hospital
      Anxiety and Depression Scale immediately prior to the offer of 2MSS. Follow-up
      questionnaires assessing psychological symptomatology were completed at 20 and 30
      weeks gestation. RESULTS: Only 37% of decisions were informed; those who
      participated in screening were more likely to have made an informed decision than
      those who did not (P = 0.01); 31% did not know that miscarriage was a possible
      consequence of diagnostic testing subsequent to an increased risk screening
      result and only 62% correctly identified that termination of pregnancy would be
      offered if Down syndrome were to be diagnosed. Short-term anxiety levels in those
      who were well informed were not significantly different from those who were
      poorly informed (P = 0.14). CONCLUSIONS: Health promotion strategies, which are
      readily applicable in clinical settings and address diverse learning needs and
      attitudes of pregnant women, are needed. The impact of antenatal screening on
      other dimensions of pregnancy psychology remains to be investigated.

PMID- 16953860
TI  - The impact of fetal fibronectin testing for women with symptoms of preterm labour
      in routine clinical practice within a New Zealand population.
AB  - AIMS: To perform a comparative analysis of antenatal management received
      according to the results of cervico-vaginal fetal fibronectin (fFN) testing, and
      to review preterm delivery rates and fFN predictive values within a New Zealand
      population of women presenting with threatened preterm labour. METHODS: Case note
      review of all fFN tests performed at Middlemore Hospital, South Auckland from
      August 2003 to March 2005 (n = 199). Data collected included risk factors for
      preterm delivery, signs and symptoms at presentation, antenatal management
      received after fFN test and outcome and delivery details. Positive and negative
      fFN results were compared. RESULTS: Women with a positive fFN were more likely to
      receive antenatal corticosteroids (96.4 vs 4.7% RR 8.74 (95% CI 5.40-14.17)) and
      tocolysis (71.4 vs 2.4% RR 8.10 (95% CI 4.49-14.59)) and to be admitted
      antenatally (96.4 vs 54.4% RR 1.77 (95% CI 1.50-2.10)) with a higher mean cost of
      treatment (967.47 NZ dollars vs 335.27 NZ dollars P < 0.05). Rates of delivery <
      34 weeks were higher in those with a positive fFN (41.9 vs 0.7% RR 62.06 (95% CI
      8.43-457.14)). CONCLUSION: Women with a positive fFN result received different
      treatment to those with a negative fFN. Use of fFN test in routine clinical
      practice allows management and resources to be targeted more appropriately and
      may limit unnecessary interventions.

PMID- 16953861
TI  - Readmission risk and metabolic, biochemical, haematological and clinical
      indicators of severity in hyperemesis gravidarum.
AB  - In a retrospective analysis of 192 cases of presumed hyperemesis gravidarum,
      there were no biochemical markers that predicted hospital readmission. There was,
      however, statistically significant negative predictive value in abnormal liver
      function tests. This could represent acute self-limited illness with a component
      of hepatitis as the cause for the clinical presentation, rather than hyperemesis.

PMID- 16953862
TI  - Tuberculosis in pregnancy - case studies and a review of Australia's screening
      process.
AB  - Few changes have occurred in the management of tuberculosis over the past two
      decades and many of the recent developments are in the area of diagnostics. The
      application of these to the pregnant population is not yet established. Two cases
      recently managed at the Royal Women's Hospital, Melbourne highlight the need for
      clinicians managing pregnant women to rethink this condition and, with changes in
      migration and epidemiology, reconsider our screening practice.

PMID- 16953863
TI  - Hyperbaric oxygen and in vitro fertilisation.

PMID- 16953864
TI  - Cosmetic tattooing: A potential transmission route for HIV?

PMID- 16953865
TI  - A rare complication of an indwelling urinary catheter - ureteral entrapment.

PMID- 16953866
TI  - A huge 'prostate-mimicking' vaginal leiomyoma with simultaneous expression of
      oestrogen and progesterone receptors.

PMID- 16953867
TI  - Re: Australian carbohydrate intolerance study in pregnant women: implications for
      the management of gestational diabetes.

PMID- 16953868
TI  - Re: Midurethral Tissue Fixation System sling.

PMID- 16953870
TI  - Re: obstetrics and gynaecology for potential trainees: is there a lack of
      experience?

PMID- 16953871
TI  - Personally addressed hand-signed letters increase questionnaire response: a meta
      analysis of randomised controlled trials.
AB  - BACKGROUND: Postal questionnaires are commonly used to collect data for health
      studies, but non-response reduces study sample sizes and can introduce bias.
      Finding ways to increase the proportion of questionnaires returned would improve
      research quality. We sought to quantify the effect on response when researchers
      address participants personally by name on letters that accompany questionnaires.
      METHODS: All randomised controlled trials in a published systematic review that
      evaluated the effect on response of including participants' names on letters that
      accompany questionnaires were included. Odds ratios for response were pooled in a
      random effects meta-analysis and evidence for changes in effects over time was
      assessed using random effects meta-regression. RESULTS: Fourteen randomised
      controlled trials were included covering a wide range of topics. Most topics were
      unrelated to health or social care. The odds of response when including
      participants' names on letters were increased by one-fifth (pooled OR 1.18, 95%
      CI 1.03 to 1.34; p = 0.015). When participants' names and hand-written signatures
      were used in combination, the effect was a more substantial increase in response
      (OR 1.45, 95% CI 1.27 to 1.66; p < 0.001), corresponding to an absolute increase
      in the proportion of questionnaires returned of between 4% and 10%, depending on
      the baseline response rate. There was no evidence that the magnitude of these
      effects had declined over time. CONCLUSION: This meta-analysis of the best
      available evidence indicates that researchers using postal questionnaires can
      increase response by addressing participants by name on cover letters. The effect
      appears to be enhanced by including hand-written signatures.

PMID- 16953872
TI  - Association between anemia and quality of life in a population sample of
      individuals with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Several studies investigated the association of anemia with health
      related quality of life (HRQL) in patients with chronic disease. However, there
      is little evidence regarding the association of anemia with HRQL in patients with
      chronic obstructive pulmonary disease (COPD). METHODS: This is a post-hoc
      analysis of a study which enrolled a population of adults aged 35-79 randomly
      selected from residents of Erie and Niagara Counties, NY, between 1996 and 2000.
      In addition to demographic information and physical measurements, we obtained
      spirometry data and hemoglobin levels. We used modified Global Initiative for
      Chronic Obstructive Lung Disease (GOLD) criteria to define COPD, and World Health
      Organization (WHO) criteria to define anemia. To assess HRQL we used the Short
      Form-36 (SF-36) to assess physical functioning (PF), physical component summary
      (PCS) measures and mental component summary (MCS) measures. RESULTS: In the
      entire study population (n = 2704), respondents with anemia had lower scores on
      the physical functioning domain [45.4 (SD10.9) vs. 49.2 (SD 9.1); p < 0.0001].
      Among patients with COPD (n = 495) the PF scores (39.9 vs. 45.4) and the PCS
      (41.9 vs. 45.9) were significantly lower in individuals with anemia compared to
      those without. In multiple regression analysis, the association between
      hemoglobin and PCS was positive (regression coefficient 0.02, p = 0.003). There
      was no significant association of hemoglobin with PF scores or the mental
      component summary measure after adjusting for covariates in patients with COPD.
      CONCLUSION: In patients with moderate to very severe COPD anemia may be
      associated with worse HRQL. However, co-morbidities may explain part or all of
      this association in these patients.

PMID- 16953873
TI  - An analysis of patient house calls in the area of Attica, Greece.
AB  - BACKGROUND: Physicians house calls to patients have been declining in many
      countries of the world. The objective of this study was to describe the patterns
      of utilization of house call services provided by SOS doctors in the area of
      Attica, Greece. METHODS: We performed a retrospective analysis of data regarding
      house call visits of patients in the area of Attica (metropolitan area of Athens
      and surrounding cities), Greece. Characteristics of patients who received house
      call services by a physician, including diagnosis, and recommended management
      plan, including advice for hospitalization were analyzed. RESULTS: SOS doctors in
      the area of Attica, Greece performed 98,009 house calls during the 5-year study
      period (1/11/2000-31/10/2005). Patients older than 65 years requested 47.8% of
      the house calls. Females requested more house calls during the studied period
      compared to males (59.4% versus 40.6%, p < 0.001). The majority of the diagnoses
      (18.4%) were infections of the upper and lower respiratory tract. 9.1% of
      patients were advised after the evaluation at home to be admitted to a hospital
      to receive inpatient services. CONCLUSION: Our analysis documents the utilization
      of house calls by SOS doctors in the area of Attica, Greece during a 5-year
      period. We believe that house calls provided by individual practitioners,
      physician group practices, or organized companies and organizations should re
      gain their well-deserved position in the modern health care systems.

PMID- 16953874
TI  - Distill: a suite of web servers for the prediction of one-, two- and three
      dimensional structural features of proteins.
AB  - BACKGROUND: We describe Distill, a suite of servers for the prediction of protein
      structural features: secondary structure; relative solvent accessibility; contact
      density; backbone structural motifs; residue contact maps at 6, 8 and 12
      Angstrom; coarse protein topology. The servers are based on large-scale ensembles
      of recursive neural networks and trained on large, up-to-date, non-redundant
      subsets of the Protein Data Bank. Together with structural feature predictions,
      Distill includes a server for prediction of Calpha traces for short proteins (up
      to 200 amino acids). RESULTS: The servers are state-of-the-art, with secondary
      structure predicted correctly for nearly 80% of residues (currently the top
      performance on EVA), 2-class solvent accessibility nearly 80% correct, and
      contact maps exceeding 50% precision on the top non-diagonal contacts. A
      preliminary implementation of the predictor of protein Calpha traces featured
      among the top 20 Novel Fold predictors at the last CASP6 experiment as group
      Distill (ID 0348). The majority of the servers, including the Calpha trace
      predictor, now take into account homology information from the PDB, when
      available, resulting in greatly improved reliability. CONCLUSION: All predictions
      are freely available through a simple joint web interface and the results are
      returned by email. In a single submission the user can send protein sequences for
      a total of up to 32k residues to all or a selection of the servers. Distill is
      accessible at the address: http://distill.ucd.ie/distill/.

PMID- 16953875
TI  - CA 15-3 is predictive of response and disease recurrence following treatment in
      locally advanced breast cancer.
AB  - BACKGROUND: Primary chemotherapy (PC) is used for down-staging locally advanced
      breast cancer (LABC). CA 15-3 measures the protein product of the MUC1 gene and
      is the most widely used serum marker in breast cancer. METHODS: We
      retrospectively investigated the role of CA 15-3 in conjunction with other
      clinico-pathological variables as a predictor of response and time to disease
      recurrence following treatment in LABC. Pre and post primary chemotherapy serum
      concentrations of CA 15-3 together with other variables were reviewed and related
      to four outcomes following primary chemotherapy (clinical response, pathological
      response, time to recurrence and time to progression). Persistently elevated CA
      15-3 after PC was considered as consecutively high levels above the cut off point
      during and after PC. RESULTS: 73 patients were included in this study. Patients
      received PC (AC or AC-T regimen) for locally advanced breast cancer. 54 patients
      underwent surgery. The median follow up was 790 days. Patients with high
      concentrations of CA 15-3 before PC treatment had a poor clinical (p = 0.013) and
      pathological (p = 0.044) response. Together with Her-2/neu expression (p = 0.009)
      and tumour lympho-vascular space invasion (LVI) (p = 0.001), a persistently
      elevated CA 15-3 post PC (p = 0.007) was an independent predictive factor of
      recurrence following treatment in LABC. CONCLUSION: Elevated CA 15-3 level is
      predictive of a poor response to chemotherapy. In addition, persistently elevated
      CA 15-3 levels post chemotherapy in conjunction with lympho-vascular invasion and
      HER2 status predict a reduced disease free survival following treatment in
      locally advanced breast cancer.

PMID- 16953876
TI  - Impaired neural networks for approximate calculation in dyscalculic children: a
      functional MRI study.
AB  - BACKGROUND: Developmental dyscalculia (DD) is a specific learning disability
      affecting the acquisition of mathematical skills in children with otherwise
      normal general intelligence. The goal of the present study was to examine
      cerebral mechanisms underlying DD. METHODS: Eighteen children with DD aged 11.2
      +/- 1.3 years and twenty age-matched typically achieving schoolchildren were
      investigated using functional magnetic resonance imaging (fMRI) during trials
      testing approximate and exact mathematical calculation, as well as magnitude
      comparison. RESULTS: Children with DD showed greater inter-individual variability
      and had weaker activation in almost the entire neuronal network for approximate
      calculation including the intraparietal sulcus, and the middle and inferior
      frontal gyrus of both hemispheres. In particular, the left intraparietal sulcus,
      the left inferior frontal gyrus and the right middle frontal gyrus seem to play
      crucial roles in correct approximate calculation, since brain activation
      correlated with accuracy rate in these regions. In contrast, no differences
      between groups could be found for exact calculation and magnitude comparison. In
      general, fMRI revealed similar parietal and prefrontal activation patterns in DD
      children compared to controls for all conditions. CONCLUSION: In conclusion,
      there is evidence for a deficient recruitment of neural resources in children
      with DD when processing analog magnitudes of numbers.

PMID- 16953877
TI  - Genetic analysis of Thailand hantavirus in Bandicota indica trapped in Thailand.
AB  - Sixty one tissue samples from several rodent species trapped in five provinces of
      Thailand were examined for the presence of hantaviral markers by enzyme
      immunoassay and immunoblotting. Four samples, all from the great bandicoot rat
      Bandicota indica, were confirmed positive for the hantaviral N-antigen. Two of
      them were trapped in Nakhon Pathom province, the other two in Nakhon Ratchasima
      province, approximately 250 km from the other trapping site. When analysed by RT
      nested PCR, all four rodents were found positive for the hantaviral S- and M
      segment nucleotide sequences. Genetic analysis revealed that the four newly
      described wild-type strains belong to Thailand hantavirus. On the phylogenetic
      trees they formed a well-supported cluster within the group of Murinae-associated
      hantaviruses and shared a recent common ancestor with Seoul virus.

PMID- 16953878
TI  - In planta transient expression as a system for genetic and biochemical analyses
      of chlorophyll biosynthesis.
AB  - BACKGROUND: Mg chelatase is a multi-subunit enzyme that catalyses the first
      committed step of chlorophyll biosynthesis. Studies in higher plants and algae
      indicate that the Mg chelatase reaction product, Mg-protoporphyrin IX plays an
      essential role in nuclear-plastid interactions. A number of Mg chelatase mutants
      have been isolated from higher plants, including semi-dominant alleles of ChlI,
      the gene encoding the I subunit of the enzyme. To investigate the function of
      higher plant CHLI, bacterial orthologues have been engineered to carry analogous
      amino acid substitutions to the higher plant mutations and the phenotypes
      examined through in vitro characterization of heterologously produced proteins.
      Here, we demonstrate the utility of a transient expression system in Nicotiana
      benthamiana for rapidly assaying mutant variants of the maize CHLI protein in
      vivo. RESULTS: Transient expression of mutant maize ChlI alleles in N.
      benthamiana resulted in the formation of chlorotic lesions within 4 d of
      inoculation. Immunoblot analyses confirmed the accumulation of maize CHLI protein
      suggesting that the chlorosis observed resulted from an interaction between maize
      CHLI and endogenous components of the N. benthamiana chlorophyll biosynthetic
      pathway. On the basis of this assay, PCR-based cloning techniques were used to
      rapidly recombine polymorphisms present in the alleles studied allowing
      confirmation of causative lesions. A PCR-based mutagenesis was conducted and
      clones assayed by transient expression. A number of novel allelic variants of
      maize ZmChlI were generated and analyzed using this assay, demonstrating the
      utility of this technique for fine mapping. CONCLUSION: Transient expression
      provides a convenient, high-throughput, qualitative assay for functional
      variation in the CHLI protein. Furthermore, we suggest that the approach used
      here would be applicable to the analysis of other plastid-localized proteins
      where gain-of-function mutations will result in readily observable mutant
      phenotypes.

PMID- 16953879
TI  - A database application for pre-processing, storage and comparison of mass spectra
      derived from patients and controls.
AB  - BACKGROUND: Statistical comparison of peptide profiles in biomarker discovery
      requires fast, user-friendly software for high throughput data analysis.
      Important features are flexibility in changing input variables and statistical
      analysis of peptides that are differentially expressed between patient and
      control groups. In addition, integration the mass spectrometry data with the
      results of other experiments, such as microarray analysis, and information from
      other databases requires a central storage of the profile matrix, where protein
      id's can be added to peptide masses of interest. RESULTS: A new database
      application is presented, to detect and identify significantly differentially
      expressed peptides in peptide profiles obtained from body fluids of patient and
      control groups. The presented modular software is capable of central storage of
      mass spectra and results in fast analysis. The software architecture consists of
      4 pillars, 1) a Graphical User Interface written in Java, 2) a MySQL database,
      which contains all metadata, such as experiment numbers and sample codes, 3) a
      FTP (File Transport Protocol) server to store all raw mass spectrometry files and
      processed data, and 4) the software package R, which is used for modular
      statistical calculations, such as the Wilcoxon-Mann-Whitney rank sum test.
      Statistic analysis by the Wilcoxon-Mann-Whitney test in R demonstrates that
      peptide-profiles of two patient groups 1) breast cancer patients with
      leptomeningeal metastases and 2) prostate cancer patients in end stage disease
      can be distinguished from those of control groups. CONCLUSION: The database
      application is capable to distinguish patient Matrix Assisted Laser Desorption
      Ionization (MALDI-TOF) peptide profiles from control groups using large size
      datasets. The modular architecture of the application makes it possible to adapt
      the application to handle also large sized data from MS/MS- and Fourier Transform
      Ion Cyclotron Resonance (FT-ICR) mass spectrometry experiments. It is expected
      that the higher resolution and mass accuracy of the FT-ICR mass spectrometry
      prevents the clustering of peaks of different peptides and allows the
      identification of differentially expressed proteins from the peptide profiles.

PMID- 16953880
TI  - Interspecific competition between entomopathogenic nematodes (Steinernema) is
      modified by their bacterial symbionts (Xenorhabdus).
AB  - BACKGROUND: Symbioses between invertebrates and prokaryotes are biological
      systems of particular interest in order to study the evolution of mutualism. The
      symbioses between the entomopathogenic nematodes Steinernema and their bacterial
      symbiont Xenorhabdus are very tractable model systems. Previous studies
      demonstrated (i) a highly specialized relationship between each strain of
      nematodes and its naturally associated bacterial strain and (ii) that mutualism
      plays a role in several important life history traits of each partner such as
      access to insect host resources, dispersal and protection against various biotic
      and abiotic factors. The goal of the present study was to address the question of
      the impact of Xenorhabdus symbionts on the progression and outcome of
      interspecific competition between individuals belonging to different Steinernema
      species. For this, we monitored experimental interspecific competition between
      (i) two nematode species: S. carpocapsae and S. scapterisci and (ii) their
      respective symbionts: X. nematophila and X. innexi within an experimental insect
      host (Galleria mellonella). Three conditions of competition between nematodes
      were tested: (i) infection of insects with aposymbiotic IJs (i.e. without
      symbiont) of both species (ii) infection of insects with aposymbiotic IJs of both
      species in presence of variable proportion of their two Xenorhabdus symbionts and
      (iii) infection of insects with symbiotic IJs (i.e. naturally associated with
      their symbionts) of both species. RESULTS: We found that both the progression and
      the outcome of interspecific competition between entomopathogenic nematodes were
      influenced by their bacterial symbionts. Thus, the results obtained with
      aposymbiotic nematodes were totally opposite to those obtained with symbiotic
      nematodes. Moreover, the experimental introduction of different ratios of
      Xenorhabdus symbionts in the insect-host during competition between Steinernema
      modified the proportion of each species in the adults and in the global
      offspring. CONCLUSION: We showed that Xenorhabdus symbionts modified the
      competition between their Steinernema associates. This suggests that Xenorhabdus
      not only provides Steinernema with access to food sources but also furnishes new
      abilities to deal with biotic parameters such as competitors.

PMID- 16953881
TI  - Acute effect of meal glycemic index and glycemic load on blood glucose and
      insulin responses in humans.
AB  - OBJECTIVE: Foods with contrasting glycemic index when incorporated into a meal,
      are able to differentially modify glycemia and insulinemia. However, little is
      known about whether this is dependent on the size of the meal. The purposes of
      this study were: i) to determine if the differential impact on blood glucose and
      insulin responses induced by contrasting GI foods is similar when provided in
      meals of different sizes, and; ii) to determine the relationship between the
      total meal glycemic load and the observed serum glucose and insulin responses.
      METHODS: Twelve obese women (BMI 33.7 +/- 2.4 kg/m2) were recruited. Subjects
      received 4 different meals in random order. Two meals had a low glycemic index
      (40-43%) and two had a high-glycemic index (86-91%). Both meal types were given
      as two meal sizes with energy supply corresponding to 23% and 49% of predicted
      basal metabolic rate. Thus, meals with three different glycemic loads (95, 45-48
      and 22 g) were administered. Blood samples were taken before and after each meal
      to determine glucose, free-fatty acids, insulin and glucagon concentrations over
      a 5-h period. RESULTS: An almost 2-fold higher serum glucose and insulin
      incremental area under the curve (AUC) over 2 h for the high- versus low-glycemic
      index same sized meals was observed (p < 0.05), however, for the serum glucose
      response in small meals this was not significant (p = 0.38). Calculated meal
      glycemic load was associated with 2 and 5 h serum glucose (r = 0.58, p < 0.01)
      and insulin (r = 0.54, p < 0.01) incremental and total AUC. In fact, when
      comparing the two meals with similar glycemic load but differing carbohydrate
      amount and type, very similar serum glucose and insulin responses were found. No
      differences were observed for serum free-fatty acids and glucagon profile in
      response to meal glycemic index. CONCLUSION: This study showed that foods of
      contrasting glycemic index induced a proportionally comparable difference in
      serum insulin response when provided in both small and large meals. The same was
      true for the serum glucose response but only in large meals. Glycemic load was
      useful in predicting the acute impact on blood glucose and insulin responses
      within the context of mixed meals.

PMID- 16953882
TI  - Peritonitis - the Western experience.
AB  - Peritonitis is a common surgical emergency. This manuscript will provide an
      overview of recent developments in the management of peritonitis in the Western
      world. Emphasis is placed on the emergence of new treatments and their impact of
      outcomes.

PMID- 16953883
TI  - Excessive weight gain after remission of depression in a schizophrenic patient
      treated with risperidone: case report.
AB  - BACKGROUND: The use of atypical antipsychotics in schizophrenic patients has been
      associated with a risk of weight gain. Similarly, recovery from depression is
      often followed by improved appetite, greater food intake and potential increase
      in weight. CASE PRESENTATION: A Caucasian 33-year-old schizophrenic female
      patient was being treated with 6 mg/day of risperidone and 15 mg/day of
      clorazepate. She developed depressive symptomatology and 40 mg/day of fluoxetine
      was gradually added to her treatment regimen for about 9 months. After the
      remission of depression, and the discontinuation of fluoxetine, she experienced
      an increase in appetite and subsequently excessive weight gain of 52 kg. Re
      administration of fluoxetine did not reverse the situation. The patient developed
      diabetes mellitus, which was successfully controlled with metformin 1700 mg/day.
      The addition at first of orlistat 360 mg/day and later of topiramate 200 mg/day
      has helped her to lose a significant part of the weight gained (30 kg).
      CONCLUSION: The case suggests a probable association between the remission of
      depressive symptomatology and weight gain in a schizophrenic patient.

PMID- 16953884
TI  - Spectrum of perforation peritonitis in India--review of 504 consecutive cases.
AB  - BACKGROUND/OBJECTIVE: Perforation peritonitis is the most common surgical
      emergency in India. The spectrum of etiology of perforation in Tropical countries
      continues to be different from its Western counterpart. The objective of the
      study was to highlight the spectrum of perforation peritonitis as encountered by
      us at Government Medical College and Hospital (GMCH), Chandigarh. METHODS: Five
      hundred and four consecutive cases of perforation peritonitis over a period of
      five years were reviewed in terms of clinical presentation, operative findings
      and postoperative course retrospectively at GMCH, Chandigarh. RESULTS: The most
      common cause of perforation in our series was perforated duodenal ulcer (289
      cases) followed by appendicitis (59 cases), gastrointestinal perforation due to
      blunt trauma abdomen (45 cases), typhoid fever (41 cases) and tuberculosis (20
      cases). Despite delay in seeking medical treatment (53%), the overall mortality
      (10%) was favourably comparable with other published series though the overall
      morbidity (50%) was unusually high. CONCLUSION: In contrast to western
      literature, where lower gastrointestinal tract perforations predominate, upper
      gastrointestinal tract perforations constitute the majority of cases in India.
      The increasing incidence of post-traumatic gastro-enteric injuries may be due to
      an increase in high speed motor vehicle accidents which warrant early recognition
      and prompt treatment to avoid serious complications and death.

PMID- 16953885
TI  - Genomic organization and evolution of the ULBP genes in cattle.
AB  - BACKGROUND: The cattle UL16-binding protein 1 (ULBP1) and ULBP2 genes encode
      members of the MHC Class I superfamily that have homology to the human ULBP
      genes. Human ULBP1 and ULBP2 interact with the NKG2D receptor to activate
      effector cells in the immune system. The human cytomegalovirus UL16 protein is
      known to disrupt the ULBP-NKG2D interaction, thereby subverting natural killer
      cell-mediated responses. Previous Southern blotting experiments identified
      evidence of increased ULBP copy number within the genomes of ruminant
      artiodactyls. On the basis of these observations we hypothesized that the cattle
      ULBPs evolved by duplication and sequence divergence to produce a sufficient
      number and diversity of ULBP molecules to deliver an immune activation signal in
      the presence of immunogenic peptides. Given the importance of the ULBPs in
      antiviral immunity in other species, our goal was to determine the copy number
      and genomic organization of the ULBP genes in the cattle genome. RESULTS:
      Sequencing of cattle bacterial artificial chromosome genomic inserts resulted in
      the identification of 30 cattle ULBP loci existing in two gene clusters. Evidence
      of extensive segmental duplication and approximately 14 Kbp of novel repetitive
      sequences were identified within the major cluster. Ten ULBPs are predicted to be
      expressed at the cell surface. Substitution analysis revealed 11 outwardly
      directed residues in the predicted extracellular domains that show evidence of
      positive Darwinian selection. These positively selected residues have only one
      residue that overlaps with those proposed to interact with NKG2D, thus suggesting
      the interaction with molecules other than NKG2D. CONCLUSION: The ULBP loci in the
      cattle genome apparently arose by gene duplication and subsequent sequence
      divergence. Substitution analysis of the ULBP proteins provided convincing
      evidence for positive selection on extracellular residues that may interact with
      peptide ligands. These results support our hypothesis that the cattle ULBPs
      evolved under adaptive diversifying selection to avoid interaction with a UL16
      like molecule whilst preserving the NKG2D binding site. The large number of ULBPs
      in cattle, their extensive diversification, and the high prevalence of bovine
      herpesvirus infections make this gene family a compelling target for studies of
      antiviral immunity.

PMID- 16953886
TI  - Specific down-regulation of XIAP with RNA interference enhances the sensitivity
      of canine tumor cell-lines to TRAIL and doxorubicin.
AB  - BACKGROUND: Apoptosis resistance occurs in various tumors. The anti-apoptotic
      XIAP protein is responsible for inhibiting apoptosis by reducing caspase-3
      activation. Our aim is to evaluate whether RNA inhibition against XIAP increases
      the sensitivity of canine cell-lines for chemotherapeutics such as TRAIL and
      doxorubicin. We used small interfering RNA's (siRNA) directed against XIAP in
      three cell-lines derived from bile-duct epithelia (BDE), mammary carcinoma
      (P114), and osteosarcoma (D17). These cell-lines represent frequently occurring
      canine cancers and are highly comparable to their human counterparts. XIAP down
      regulation was measured by means of quantitative PCR (Q-PCR) and Western
      blotting. The XIAP depleted cells were treated with a serial dilution of TRAIL or
      doxorubicin and compared to mock- and nonsense-treated controls. Viability was
      measured with a MTT assay. RESULTS: All XIAP siRNA treated cell-lines showed a
      mRNA down-regulation over 80 percent. Western blot analysis confirmed mRNA
      measurements. No compensatory effect of IAP family members was seen in XIAP
      depleted cells. The sensitivity of XIAP depleted cells for TRAIL was highest in
      BDE cells with an increase in the ED50 of 14-fold, compared to mock- and nonsense
      treated controls. The sensitivity of P114 and D17 cell-lines increased six- and
      five-fold, respectively. Doxorubicin treatment in XIAP depleted cells increased
      sensitivity in BDE cells more than eight-fold, whereas P114 and D17 cell-lines
      showed an increase in sensitivity of three- and five-fold, respectively.
      CONCLUSION: XIAP directed siRNA's have a strong sensitizing effect on TRAIL
      reduced cell-viability and a smaller but significant effect with the DNA damaging
      drug doxorubicin. The increase in efficacy of chemotherapeutics with XIAP
      depletion provides the rationale for the use of XIAP siRNA's in insensitive
      canine tumors.

PMID- 16953887
TI  - Neuroendocrine differentiation and neuroendocrine morphology as two different
      patterns in large-cell bronchial carcinomas: outcome after complete resection.
AB  - BACKGROUND: In 1999, large-cell neuroendocrine carcinoma of the lung was
      introduced by the World Health Organization (WHO) as a new tumor entity in the
      group of non-small cell, epithelial tumors, a differentiated classification of
      neuroendocrine tumors of the lung not existing until this time. Scientific
      knowledge on prognosis and therapy of these tumors, especially between those with
      neuroendocrine morphology only and those showing additional expression of
      neuroendocrine markers, is fragmentary. In this analysis, we studied the clinical
      behavior and the prognosis of these two rare tumor entities. PATIENTS AND
      METHODS: The analysis comprises 12 patients of a total of 2053, who underwent
      thoracotomy for non small-cell lung carcinoma between 1997 and 2005 in the
      Department of Thoracic Surgery at the University Hospital of Freiburg. Clinical
      data, pathological examinations as well as complete follow-up were reviewed from
      large-cell carcinoma with neuroendocrine morphology only (n=4) and from large
      cell carcinoma expressing neuroendocrine markers (n=8). RESULTS: The median
      survival of patients with neuroendocrine morphology was 30 months (11-96 months).
      In the patient group showing the expression of neuroendocrine markers, the median
      survival time was 20 months (2-26 months). Tumor recurrences occurred in the
      group with neuroendocrine morphology, without exception, in the form of distant
      metastases and in the group with neuroendocrine markers as intrapulmonary
      metastases. CONCLUSION: Large-cell neuroendocrine carcinomas of the lung show
      aggressive behavior with a poor prognosis. Expression of neuroendocrine markers
      markedly reduce tumor-free interval as well as survival and might influence the
      site of metastases.

PMID- 16953888
TI  - Cri du Chat syndrome.
AB  - The Cri du Chat syndrome (CdCS) is a genetic disease resulting from a deletion of
      variable size occurring on the short arm of chromosome 5 (5p-). The incidence
      ranges from 1:15,000 to 1:50,000 live-born infants. The main clinical features
      are a high-pitched monochromatic cry, microcephaly, broad nasal bridge,
      epicanthal folds, micrognathia, abnormal dermatoglyphics, and severe psychomotor
      and mental retardation. Malformations, although not very frequent, may be
      present: cardiac, neurological and renal abnormalities, preauricular tags,
      syndactyly, hypospadias, and cryptorchidism. Molecular cytogenetic analysis has
      allowed a cytogenetic and phenotypic map of 5p to be defined, even if results
      from the studies reported up to now are not completely in agreement. Genotype
      phenotype correlation studies showed a clinical and cytogenetic variability. The
      identification of phenotypic subsets associated with a specific size and type of
      deletion is of diagnostic and prognostic relevance. Specific growth and
      psychomotor development charts have been established. Two genes, Semaphorin F
      (SEMAF) and delta-catenin (CTNND2), which have been mapped to the "critical
      regions", are potentially involved in cerebral development and their deletion may
      be associated with mental retardation in CdCS patients. Deletion of the
      telomerase reverse transcriptase (hTERT) gene, localised to 5p15.33, could
      contribute to the phenotypic changes in CdCS. The critical regions were recently
      refined by using array comparative genomic hybridisation. The cat-like cry
      critical region was further narrowed using quantitative polymerase chain reaction
      (PCR) and three candidate genes were characterised in this region. The diagnosis
      is based on typical clinical manifestations. Karyotype analysis and, in doubtful
      cases, FISH analysis will confirm the diagnosis. There is no specific therapy for
      CdCS but early rehabilitative and educational interventions improve the prognosis
      and considerable progress has been made in the social adjustment of CdCS
      patients.

PMID- 16953889
TI  - Genome sequence alterations detected upon passage of Burkholderia mallei ATCC
      23344 in culture and in mammalian hosts.
AB  - BACKGROUND: More than 12,000 simple sequence repeats (SSRs) have been identified
      in the genome of Burkholderia mallei ATCC 23344. As a demonstrated mechanism of
      phase variation in other pathogenic bacteria, these may function as mutable loci
      leading to altered protein expression or structure variation. To determine if
      such alterations are occurring in vivo, the genomes of various single-colony
      passaged B. mallei ATCC 23344 isolates, one from each source, were sequenced from
      culture, a mouse, a horse, and two isolates from a single human patient, and the
      sequence compared to the published B. mallei ATCC 23344 genome sequence. RESULTS:
      Forty-nine insertions and deletions (indels) were detected at SSRs in the five
      passaged strains, a majority of which (67.3%) were located within noncoding
      areas, suggesting that such regions are more tolerant of sequence alterations.
      Expression profiling of the two human passaged isolates compared to the strain
      before passage revealed alterations in the mRNA levels of multiple genes when
      grown in culture. CONCLUSION: These data support the notion that genome
      variability upon passage is a feature of B. mallei ATCC23344, and that within a
      host B. mallei generates a diverse population of clones that accumulate genome
      sequence variation at SSR and other loci.

PMID- 16953890
TI  - Extensive myocardial infiltration by hemopoietic precursors in a patient with
      myelodysplastic syndrome.
AB  - BACKGROUND: Although myocardial infiltration with leukemic blasts is a known
      finding in patients with acute leukemia, this phenomenon in myelodysplasia is not
      reported in the literature. Cardiac symptoms in patients with myelodysplasia are
      often due to anemia and may be due to iron overload and side effects of therapy.
      CASE PRESENTATION: Herein we report the first case of neoplastic infiltration of
      the heart with associated myocardial necrosis in a patient with myelodysplasia.
      It was associated with unicellular and multifocal geographic areas of necrosis in
      the left ventricle and the interventricular septum. It is likely that cardiac
      compromise in our patient was due to a combination of restrictive cardiomyopathy
      due to leukemic infiltration, concomitant anemia, cardiac dilatation, conduction
      blocks and myocardial necrosis. Myocardial necrosis was most likely due to a
      combination of ischemic damage secondary to anemia and prolonged hypotension and
      extensive leukemic infiltration. Markedly rapid decrease in ejection fraction
      from 66% to 33% also suggests the role of ischemia, since leukemic infiltration
      is not expected to cause this degree of systolic dysfunction over a 24-hour
      period. The diagnosis was not suspected during life due to concomitant signs and
      symptoms of anemia, pulmonary infections, and pericardial and pleural effusions.
      The patient succumbed to cardiac failure. CONCLUSION: Hemopoietic cell
      infiltration was not considered in the differential diagnosis and contributed to
      this patient's morbidity and mortality. This case highlights the clinical
      importance of considering myocardial infiltration in patients with myelodysplasia
      and cardiac symptoms.

PMID- 16953891
TI  - Internalization of ferromagnetic nanowires by different living cells.
AB  - The ability of living cells, either adherent or suspended, to internalize nickel
      nanowires is demonstrated for MC3T3-E1, UMR106-tumour and Marrow-Stromal cells.
      Nanowires were produced by electrodeposition, 20 mum long and 200 nm in diameter.
      Cell separation and manipulation was achieved for the three cell types. Applied
      magnetic field successfully oriented the internalized nanowires but no clear
      anisotropy is induced on the adherent cells. Nanowires tend to bind to cytoplasm
      metalloproteins and trigger lysosome reorganization around the nucleus. This work
      demonstrates the applications of nanowires in adherent and suspended cells for
      cell separation and manipulation, and further explore into their role in
      nanobiotechnology.

PMID- 16953892
TI  - The signaling helix: a common functional theme in diverse signaling proteins.
AB  - BACKGROUND: The mechanism by which the signals are transmitted between receptor
      and effector domains in multi-domain signaling proteins is poorly understood.
      RESULTS: Using sensitive sequence analysis methods we identify a conserved
      helical segment of around 40 residues in a wide range of signaling proteins,
      including numerous sensor histidine kinases such as Sln1p, and receptor guanylyl
      cyclases such as the atrial natriuretic peptide receptor and nitric oxide
      receptors. We term this helical segment the signaling (S)-helix and present
      evidence that it forms a novel parallel coiled-coil element, distinct from
      previously known helical segments in signaling proteins, such as the Dimerization
      Histidine phosphotransfer module of histidine kinases, the intra-cellular domains
      of the chemotaxis receptors, inter-GAF domain helical linkers and the alpha
      helical HAMP module. Analysis of domain architectures allowed us to reconstruct
      the domain-neighborhood graph for the S-helix, which showed that the S-helix
      almost always occurs between two signaling domains. Several striking patterns in
      the domain neighborhood of the S-helix also became evident from the graph. It
      most often separates diverse N-terminal sensory domains from various C-terminal
      catalytic signaling domains such as histidine kinases, cNMP cyclase, PP2C
      phosphatases, NtrC-like AAA+ ATPases and diguanylate cyclases. It might also
      occur between two sensory domains such as PAS domains and occasionally between a
      DNA-binding HTH domain and a sensory domain. The sequence conservation pattern of
      the S-helix revealed the presence of a unique constellation of polar residues in
      the dimer-interface positions within the central heptad of the coiled-coil formed
      by the S-helix. CONCLUSION: Combining these observations with previously reported
      mutagenesis studies on different S-helix-containing proteins we suggest that it
      functions as a switch that prevents constitutive activation of linked downstream
      signaling domains. However, upon occurrence of specific conformational changes
      due to binding of ligand or other sensory inputs in a linked upstream domain it
      transmits the signal to the downstream domain. Thus, the S-helix represents one
      of the most prevalent functional themes involved in the flow of signals between
      modules in diverse prokaryote-type multi-domain signaling proteins. REVIEWERS:
      This article was reviewed by Frank Eisenhaber, Arcady Mushegian and Sandor
      Pongor.

PMID- 16953893
TI  - Cyclin D1 and p16 expression in recurrent nasopharyngeal carcinoma.
AB  - BACKGROUND: Cyclin D1 and p16 are involved in the regulation of G1 checkpoint and
      may play an important role in the tumorigenesis of nasopharyngeal carcinoma
      (NPC). Previous studies have examined the level of expression of cyclin D1 and
      p16 in primary untreated NPC but no such information is available for recurrent
      NPC. We set out in this study to examine the expression level of cyclin D1 and
      p16 in recurrent NPC that have failed previous treatment with radiation +/-
      chemotherapy. PATIENTS AND METHODS: A total of 42 patients underwent salvage
      nasopharyngectomy from 1984 to 2001 for recurrent NPC after treatment failure
      with radiation +/- chemotherapy. Twenty-seven pathologic specimens were available
      for immunohistochemical study using antibodies against cyclin D1 and p16.
      RESULTS: Positive expression of cyclin D1 was observed in 7 of 27 recurrent NPC
      specimens (26%) while positive p16 expression was seen in only 1 of 27 recurrent
      NPC (4%). CONCLUSION: While the level of expression of cyclin D1 in recurrent NPC
      was similar to that of previously untreated head and neck cancer, the level of
      p16 expression in recurrent NPC samples was much lower than that reported for
      previously untreated cancer. The finding that almost all (96%) of the recurrent
      NPC lack expression of p16 suggested that loss of p16 may confer a survival
      advantage by making cancer cells more resistant to conventional treatment with
      radiation +/- chemotherapy. Further research is warranted to investigate the
      clinical use of p16 both as a prognostic marker and as a potential therapeutic
      target.

PMID- 16953894
TI  - RNA:protein ratio of the unicellular organism as a characteristic of phosphorous
      and nitrogen stoichiometry and of the cellular requirement of ribosomes for
      protein synthesis.
AB  - BACKGROUND: Mean phosphorous:nitrogen (P:N) ratios and relationships of P:N
      ratios with the growth rate of organisms indicate a surprising similarity among
      and within microbial species, plants, and insect herbivores. To reveal the
      cellular mechanisms underling this similarity, the macromolecular composition of
      seven microorganisms and the effect of specific growth rate (SGR) on RNA:protein
      ratio, the number of ribosomes, and peptide elongation rate (PER) were analyzed
      under different conditions of exponential growth. RESULTS: It was found that P:N
      ratios calculated from RNA and protein contents in these particular organisms
      were in the same range as the mean ratios reported for diverse organisms and had
      similar positive relationships with growth rate, consistent with the growth-rate
      hypothesis. The efficiency of protein synthesis in microorganisms is estimated as
      the number of active ribosomes required for the incorporation of one amino acid
      into the synthesized protein. This parameter is calculated as the SGR:PER ratio.
      Experimental and theoretical evidence indicated that the requirement of ribosomes
      for protein synthesis is proportional to the RNA:protein ratio. The constant of
      proportionality had the same values for all organisms, and was derived
      mechanistically from the characteristics of the protein-synthesis machinery of
      the cell (the number of nucleotides per ribosome, the average masses of
      nucleotides and amino acids, the fraction of ribosomal RNA in the total RNA, and
      the fraction of active ribosomes). Impairment of the growth conditions decreased
      the RNA:protein ratio and increased the overall efficiency of protein synthesis
      in the microorganisms. CONCLUSION: Our results suggest that the decrease in
      RNA:protein and estimated P:N ratios with decrease in the growth rate of the
      microorganism is a consequence of an increased overall efficiency of protein
      synthesis in the cell resulting from activation of the general stress response
      and increased transcription of cellular maintenance genes at the expense of
      growth related genes. The strong link between P:N stoichiometry, RNA:protein
      ratio, ribosomal requirement for protein synthesis, and growth rate of
      microorganisms indicated by the study could be used to characterize the N and P
      economy of complex ecosystems such as soils and the oceans.

PMID- 16953895
TI  - Prospective randomized study comparing the Teleflex Medical SaphLITE Retractor to
      the Ethicon CardioVations Clearglide Endoscopic System.
AB  - BACKGROUND: Several minimally invasive saphenous vein harvesting techniques have
      been developed to reduce morbidities associated with coronary artery bypass
      grafting. This prospective, randomized study was designed to compare two commonly
      used minimally invasive saphenous vein harvesting techniques, the SaphLITE
      Retractor System (Teleflex Medical) and the Clearglide Endoscopic Vessel
      Harvesting System (Ethicon CardioVations, Inc.). METHODS: Between January 2003
      and March 2004, a total of 200 patients scheduled for primary, nonemergent
      coronary artery bypass grafting, with or without concomitant procedures were
      randomized into two groups: SaphLITE (n = 100) and Clearglide (n = 100). Pre-,
      intra- and postoperative data was collected and subjected to statistical
      analysis. Randomization provided homogenous groups with respect to preoperative
      risk factors. RESULTS: Harvest location for the SaphLITE group was thigh (n =
      40), lower leg (n = 5) and both lower leg and thigh (n = 55). The location of
      harvest for the Clearglide group was thigh (n = 3), lower leg (n = 16) and both
      lower leg and thigh (n = 81). The mean incision length was 3.6 cm (range, 2-6) in
      the SaphLITE group versus 2.1 cm (range, 1-4) in the Clearglide group (p < 0.05).
      The total incision length was 12.9 cm versus 8.9 (p < 0.05) in the SaphLITE and
      Clearglide groups. Conversion to the open technique occurred in 5 SaphLITE
      patients and 7 Clearglide patients. Intraoperative leg exploration for bleeding
      occurred in two of the Clearglide patients and none of the SaphLITE patients.
      Post-operative complications specifically related to minimally invasive
      harvesting technique, including a two-week post-discharge visit, were not
      statistically different between the groups. CONCLUSION: The saphenous vein can be
      safely harvested utilizing the SaphLITE and Clearglide systems. While the
      Clearglide system allows for fewer incisions (number and length) and less harvest
      time, these benefits may be outweighed by the increased cost of the Clearglide
      system compared to the SaphLITE retractor.

PMID- 16953896
TI  - The consequences of obesity on trauma, emergency surgery, and surgical critical
      care.
AB  - The era of the acute care surgeon has arrived and this "new" specialty will be
      expected to provide trauma care, emergency surgery, and surgical critical care to
      a variety of patients arriving at their institution. With the exception of
      practicing bariatric surgeons, many general surgeons have limited experience
      caring for obese patients. Obese patients manifest unique physiology and
      pathophysiology, which can influence a surgeon's decision-making process.
      Following trauma, obese patients sustain different injuries than lean patients
      and have worse outcomes. Emergency surgery diseases may be difficult to diagnose
      in the obese patient and obesity is associated with increased complications in
      the postoperative patient. Caring for an obese patient in the surgical ICU
      presents a distinctive challenge and may require alterations in care. The
      following review should act as an overview of the pathophysiology of obesity and
      how obesity modifies the care of trauma, emergency surgery, and surgical critical
      care patients.

PMID- 16953897
TI  - Endoscopic sinus surgery for maxillary sinus mucoceles.
AB  - BACKGROUND: Maxillary sinus mucoceles are relatively rare among all paranasal
      sinus mucoceles. With the introduction of endoscopic sinus surgical techniques,
      rhinologic surgeons prefer transnasal endoscopic management of sinus mucoceles.
      The aim of this study is to describe the clinical presentation of maxillary sinus
      mucoceles and to establish the efficacy of endoscopic management of sinus
      mucoceles. METHODS: Between 2003 and 2005, 14 patients underwent endoscopic sinus
      surgery for maxillary sinus mucocele. The presenting sign and symptoms,
      radiological findings, surgical management and need for revision surgery were
      reviewed. RESULTS: There were eight males and six females with an age range of 14
      to 65. Ten patients complained of nasal obstruction, five of nasal drainage, five
      of cheek pressure or pain and one of proptosis of the eye and cheek swelling. The
      maxillary sinus and ipsilateral ethmoid sinus involvement on computed tomographic
      studies was seen in 4 patients. Four patients had history of endoscopic
      ethmoidectomy surgery for ethmoid sinusitis and one had Caldwell-Luc operation in
      the past. Ethmoidectomy with middle meatal antrostomy and marsupialization of the
      mucocele was performed in all patients. Postoperative follow-up ranged between 8
      to 48 months. All patients had a patent middle meatal antrostomy and healthy
      maxillary sinus mucosa. No patients need revision surgery. CONCLUSION: The most
      common causes of mucoceles are chronic infection, allergic sinonasal disease,
      trauma and previous surgery. In 64% of the patients of our study cause remains
      uncertain. Endoscopic sinus surgery is an effective treatment for maxillary sinus
      mucoceles with a favorable long-term outcome.

PMID- 16953898
TI  - Recent translational research: circulating tumor cells in breast cancer patients.
AB  - In breast cancer patients, hematogenous tumor cell dissemination can be detected,
      even at the single cell level, by applying immunocytochemical and molecular
      assays. Various methods for the detection of circulating tumor cells in the
      peripheral blood have been described. Results from recently reported studies
      suggest that circulating tumor cell levels may serve as a prognostic marker and
      for the early assessment of therapeutic response in patients with metastatic
      breast cancer. However, in early-stage breast cancer, the impact of circulating
      tumor cells is less well established than the presence of disseminated tumor
      cells in bone marrow; several clinical studies have demonstrated that cells of
      the latter type are an independent prognostic factor at primary diagnosis. In
      this article we briefly summarize recent studies examining the presence of
      circulating tumor cells in the blood and discuss further clinical applications.

PMID- 16953899
TI  - The pulmonary artery catheter: the tool versus treatments based on the tool.
AB  - The pulmonary artery catheter (PAC) is a powerful tool that has been used
      extensively in the assessment and monitoring of cardiovascular physiology. Gross
      misinterpretation of data gathered by the PAC is common, and its routine use
      without any specific interventions has not been shown to influence outcome.
      However, there currently is no evidence from randomized, controlled trials that
      any diagnostic or monitoring tool used in intensive care patients improves
      outcome. Studies evaluating the use of the PAC have included numerous potential
      confounding factors, and should be interpreted with caution. The information
      obtained with the PAC should be used to find better treatment strategies, and
      these strategies, instead of the tool itself, should be tested in clinical
      trials.

PMID- 16953900
TI  - Bench-to-bedside review: potential strategies to protect or reverse mitochondrial
      dysfunction in sepsis-induced organ failure.
AB  - The pathogenesis of sepsis-induced multiple organ failure may crucially depend on
      the development of mitochondrial dysfunction and consequent cellular energetic
      failure. According to this hypothesis, interventions aimed at preventing or
      reversing mitochondrial damage may have major clinical relevance, although the
      timing of such interventions will be critical to both ensuring benefit and
      avoiding harm. Early correction of tissue hypoxia, strict control of glycaemia,
      and modulation of oxidative and nitrosative stress may afford protection during
      the initial, acute systemic inflammatory response. The regulated induction of a
      hypometabolic state resembling hibernation may protect the cells from dying once
      energy failure has developed, allowing the possibility of functional recovery.
      Repair of damaged organelles through stimulation of mitochondrial biogenesis and
      reactivation of cellular metabolism may accelerate resolution of the multiple
      organ failure syndrome.

PMID- 16953901
TI  - Senior moments.
AB  - The problem with reaching 'senior faculty' status is the feeling that you have
      nothing much to contribute except experience, but the recently announced
      Neanderthal Genome Project might put things into perspective.

PMID- 16953902
TI  - Feature-level exploration of a published Affymetrix GeneChip control dataset.
AB  - A comment on Preferred analysis methods for Affymetrix GeneChips revealed by a
      wholly defined control dataset by SE Choe, M Boutros, AM Michelson, GM Church and
      MS Halfon. Genome Biology 2005, 6:R16.

PMID- 16953904
TI  - Definition and current evaluation of subfertile men.
AB  - Male infertility affects 10% of reproductive aged couples worldwide and is
      treatable in many cases. In addition to other well-described etiologies, genetic
      causes of male infertility are now more commonly diagnosed. Using principles of
      evidence-based medicine, this review outlines diagnostic and treatments options
      to inform clinical management. In order of importance, randomized controlled
      clinical trials, basic scientific studies, meta-analyses, case-controlled cohort
      studies, best-practice policy recommendations and reviews from peer-reviewed
      literature were incorporated that provide organized and timely guidelines to the
      current management of male infertility. The strength of evidence for treatment
      recommendations is also classified when appropriate.

PMID- 16953905
TI  - Primary reconstruction is a good option in the treatment of urinary fistula after
      kidney transplantation.
AB  - OBJECTIVES: urinary fistula is a morbid complication after renal transplantation
      leading to graft losses and patient death. We review and update our data on
      urinary fistula after renal transplantation and the outcome after surgical and
      conservative management. MATERIALS AND METHODS: the charts of 1046 renal
      transplants were reviewed. Transplants were performed through an extended
      inguinotomy; vascular anastomoses to the iliac vessels and urinary reconstruction
      accomplished through the Gregoir technique. Fistulae were diagnosed by urinary
      leaks through the incision or by the occurrence of a collection in the iliac
      fossa. Patient was treated surgically or conservatively according to the
      characteristics of the fistula and patient clinical status. RESULTS: Thirty one
      fistulae were diagnosed (2.9%). Twenty nine leaks due to ureteral necrosis and 2
      due to reimplantation fault. The incidence of leaks among cadaver and live donor
      transplants was 3.22% and 2.63%, respectively (p = 0.73). Among diabetic and non
      diabetic patients the incidence of urinary leaks was 6.4% and 2.6%, respectively
      (p = 0.049). Treatment consisted in anastomosis of the graft ureter or pelvis
      with the ureter of the recipient in 17 cases with success in 13 (76.5%).
      Prolonged bladder drainage was employed in 7 cases and the fistula healed in 4
      (57%). Ureteral reimplantation was performed in 3 cases and did not work in any
      of them. Ureteral ligature plus nephrostomy was employed in two cases and worked
      in one (50%). Percutaneous nephrostomy and ureteral stenting with double J
      catheter were employed in one case each and worked in both. CONCLUSIONS: The
      anastomosis of the graft ureter with the ureter of the recipient is a good method
      for treating urinary fistulae after renal transplantation when local and systemic
      conditions are good. Ureteral ligature associated to nephrostomy should be
      applied in cases of unfavorable local conditions or clinically unstable patients.

PMID- 16953906
TI  - Comparison of relative renal function measured with either 99mTc-DTPA or 99mTc-EC
      dynamic scintigraphies with that measured with 99mTc-DMSA static scintigraphy.
AB  - OBJECTIVE: The aim of this study was to compare the renal function measured with
      either 99mTc-DTPA or 99mTc-EC dynamic scintigraphies with that measured using
      99mTc-DMSA static scintigraphy. METHODS: the values of relative renal function
      measured in 111 renal dynamic scintigraphies performed either with 99mTc-DTPA (55
      studies) or with 99mTc-EC (56 studies) were compared with the relative function
      measured using 99mTc-DMSA static scintigraphy performed within a 1-month period.
      The comparisons were performed using Wilcoxon signed rank test. The number of
      99mTc-DTPA and 99mTc-EC studies that presented relative renal function different
      by more than 5% from that measured with 99mTc-DMSA, using chi square test were
      also compared. RESULTS: the relative renal function measured with 99mTc-EC is not
      statistically different from that measured with 99mTc-DMSA (p = 0.97). The
      relative renal function measured with 99mTc-DTPA was statistically different from
      that measured using 99mTc-DMSA, but with a borderline statistical significance (p
      = 0.05). The number of studies with relative renal function different by more
      than 5% from that measured with 99mTc-DMSA is higher for the 99mTc-DTPA
      scintigraphy (p = 0.04) than for 99mTc-EC. CONCLUSION: the relative renal
      function measured with 99mTc-EC dynamic scintigraphy is comparable with that
      measured with 99mTc-DMSA static scintigraphy, while the relative renal function
      measured with 99mTc-DTPA dynamic scintigraphy presents a significant statistical
      difference from that measured with 99mTc-DMSA static scintigraphy.

PMID- 16953908
TI  - Salvage conformal radiotherapy for biochemical recurrent prostate cancer after
      radical prostatectomy.
AB  - OBJECTIVE: Assess the results of salvage conformal radiotherapy in patients with
      biochemical failure after radical prostatectomy and identify prognostic factors
      for biochemical recurrence and toxicity of the treatment. MATERIALS AND METHODS:
      From June 1998 to November 2001, 35 patients were submitted to conformal
      radiotherapy for PSA > or = 0.2 ng/mL in progression after radical prostatectomy
      and were retrospectively analyzed. The mean dose of radiation in prostatic bed
      was of 77.4 Gy (68-81). Variables related to the treatment and to tumor were
      assessed to identify prognostic factors for biochemical recurrence after salvage
      radiotherapy. RESULTS: The median follow-up was of 55 months (17-83). The
      actuarial survival rates free of biochemical recurrence and free of metastasis at
      a distance of 5 years were 79.7% e 84.7%, respectively. The actuarial global
      survival rate in 5 years was 96.1%. The actuarial survival rate free of
      biochemical recurrence in 5 years was 83.3% with PSA pre-radiotherapy < or = 1,
      100% when > 1 and < or = 2, and 57.1% when > 2 (p = 0.023). Dose > 70 Gy in 30%
      of the bladder volume implied in more acute urinary toxicity (p = 0.035). The
      mean time for the development of late urinary toxicity was 21 months (12-51).
      Dose > 55 Gy in 50%bladder volume implied in more late urinary toxicity (p =
      0.018). A patient presented late rectal toxicity of 2nd grade. CONCLUSIONS:
      Conformal radiotherapy showed to be effective for the control of biochemical
      recurrence after radical prostatectomy. Patients with pre-therapy PSA < or = 2
      ng/mL have more biochemical control.

PMID- 16953907
TI  - Tension free monofilament macropore polypropylene mesh (Gynemesh PS) in female
      genital prolapse repair.
AB  - OBJECTIVES: To review intraoperative and postoperative complications associated
      to the correction of cystocele and rectocele with polypropylene mesh macropore
      monofilament (Gynemesh PS) using transvaginal free tension technique. MATERIALS
      AND METHODS: Prospective study of patients that have been submitted to correction
      of cystocele and/or rectocele between November 2004 and August 2005 in the
      Urogynecology and Vaginal Surgery Unit of Gynecology and Obstetrics Department,
      Las Condes Clinic. Mesh was used in 31 patients: 9 for cystocele, 11 for
      rectocele, and 11 for concomitant meshes. Total mesh used 42. Media age 55 years
      old, weight 64 kilograms. In 7 patients we used a third mesh for correction of
      urinary incontinence by TVT-O technique. RESULTS: They did not present
      intraoperative complications, neither in immediate or delayed postoperative time.
      We did not observe hematoma, infection, erosion or exposition mesh. Healing of
      cystocele and rectocele was obtained in 100% of patients, with a pursuit between
      1 and 8 months. DISCUSSION: The use of prosthetic polypropylene monofilament
      macropore mesh in the correction of cystocele and/or rectocele, by transvaginal
      route with tension free technique seems to be a safe and effective surgery
      procedure.

PMID- 16953909
TI  - Management of rectal injury during laparoscopic radical prostatectomy.
AB  - PURPOSE: Because laparoscopic radical prostatectomy remains a challenging
      procedure, rectal injury is always a potential complication. We review the
      incidence of rectal injuries at our institution in the first 110 consecutive
      laparoscopic extraperitoneal radical prostatectomies. MATERIALS AND METHODS: Nine
      (8%) out of the first 110 laparoscopic extraperitoneal radical prostatectomies
      performed between December 2001 and February 2004, were complicated by rectal
      injury. Mean patient age was 64.9 years (range 52 to 74) and mean prostate
      specific antigen was 11.45 ng/mL (range 4.8 to 37.4). Median preoperative Gleason
      score was 6 (range 4 to 8) and clinical stage was T1c, T2a, T2b in 6, 2 and 1
      patient, respectively. Mean operative time was 228 minutes (range 150 to 300).
      RESULTS: From 9 injuries, 6 were diagnosed and repaired intraoperatively and 3
      were diagnosed postoperatively. From the 6 cases of intraoperative diagnosis and
      repair, 3 patients healed primarily without colostomy and a recto-urinary fistula
      was evidenced by pneumaturia in the remaining three. These 3 patients were
      managed conservatively with urethral catheterization during 30 days. One of the
      patients required secondary fistula repair by anterior transphincteric, transanal
      surgical approach (ASTRA). Urinary fistula was diagnosed postoperatively on 3
      patients. A diverting colostomy was performed on one patient with secondary
      fistula repair by ASTRA. Another patient required laparotomy due to peritonitis
      and urinary fistula was later managed with ASTRA. On the third patient
      conservative management with urethral catheter was successful. All fistulas
      repaired with ASTRA evolved uneventfully. There was no perioperative mortality.
      CONCLUSIONS: Rectal injury during laparoscopic radical prostatectomy can be
      managed intraoperatively or by a minimally invasive procedure without the need of
      colostomy. Laparoscopic radical prostatectomy is a challenging procedure and is
      associated with a very flat learning curve; the incidence of rectal injuries is
      prone to diminish with experience.

PMID- 16953910
TI  - Association between testicular microlithiasis, testicular cancer, cryptorchidism
      and history of ascending testis.
AB  - OBJECTIVE: To prospectively determine the prevalence of testicular microlithiasis
      in symptomatic patients who were referred for scrotal ultrasound examination and
      to evaluate the possible association of testicular microlithiasis with testicular
      cancer and other conditions such as cryptorchidism or history of ascending
      testis. MATERIALS AND METHODS: 391 men who were referred to our institutions
      between July 2002 and May 2005 for any type of symptoms from the testicles,
      underwent physical and scrotal ultrasound examination. The presence of testicular
      microlithiasis, the number of lesions and the involvement of both testicles in
      relation to the symptoms as well as the coexistence of other lesions were
      studied. RESULTS: Eighteen (4.6%) of 391 men enrolled into the study had
      testicular microlithiasis. Two out of the eighteen patients (11%) had concomitant
      testicular cancer, which was confirmed by pathological evaluation of the
      orchidectomy specimen. One of the patients with testicular microlithiasis
      presented a rising in biochemical tumor markers (LDH, and HCG) and underwent
      orchidectomy one year later. Five of the remaining 373 (1.3%) patients without
      microlithiasis were diagnosed with testicular cancer. Thirty six men reported
      having a history of ascending testis, but none of them was found with testicular
      cancer. Two cases of testicular torsion in a cryptorchid position had testicular
      microlithiasis, but the orchidectomy specimen (after surgery) was negative for
      testicular cancer. The correlation between testicular cancer and testicular
      microlithiasis found in our study was statistically significant (p < 0.05).
      CONCLUSION: There seems to be an association between testicular microlithiasis
      and testicular cancer.

PMID- 16953911
TI  - Intrarenal pseudoaneurysm after percutaneous nephrolithotomy. Angiotomographic
      assessment and endovascular management.
AB  - We report a case of intrarenal pseudoaneurysm of the right kidney after
      percutaneous nephrolithotomy (PCNL) in supine position. Diagnosis was established
      by angiotomography with a 3-D reconstruction. Treatment was successfully achieved
      by endovascular occlusion using N-butyl-2-cyanoacrylate.

PMID- 16953912
TI  - Laparoscopic resection of metastatic pelvic liposarcoma.
AB  - We report a pelvic liposarcoma originating from the left spermatic cord that
      recurred following inadequate excision. In our case, the tumor was resected
      without performing orchiectomy previously. The patient was managed by
      laparoscopic resection, before undergoing radical orchiectomy in the left
      inguinal region. To our knowledge, no case of laparoscopic resection for the
      recurrent liposarcoma has been described. In addition, the present case serves to
      demonstrate that radical orchiectomy with wide excision is needed for
      paratesticular tumor.

PMID- 16953913
TI  - Primary renal angiosarcoma.
AB  - Primary renal Angiosarcoma is a rare neoplasm and only 24 cases have been
      reported in specialized literature. We describe a case of primary renal
      angiosarcoma in a patient presenting with hematuria, palpable abdominal mass,
      left flank pain and anemia. A computerized tomography of the abdomen with
      contrast medium showed a tumor with 15 cm diameter, in the upper pole of the left
      kidney, with a low-density central area, suggesting necrosis or hemorrhage.
      Diagnosis was given in a morphologic base and proven by an immunohistochemical
      study. Primary renal angiosarcoma should be included among differential diagnosis
      of retroperitoneal hematoma and hemorrhagic renal tumors.

PMID- 16953914
TI  - Dietl's crisis: an under-recognized clinical entity in the pediatric population.
AB  - OBJECTIVE: To characterize and determine whether patients with recurrent
      abdominal symptoms and associated ureteropelvic junction obstruction (UPJO)
      (Dietl's crisis) are effectively treated by pyeloplasty and to determine criteria
      for evaluating UPJO in childhood abdominal pain. MATERIALS AND METHODS: A
      retrospective chart review from 1998 to 2001 was performed to identify patients
      with Dietl's crisis and associated UPJO. Chart review included presenting
      symptoms, location of lesion, condition of the affected renal unit, referral
      method, and surgery success. RESULTS: Eight patients (7 male and 1 female) were
      identified with Dietl's crisis. All eight were initially misdiagnosed and spent
      at least a year with significant pain symptoms before being properly diagnosed.
      Only one patient had associated urologic complaints. Renal scan split functions
      of the affected renal unit ranged from 34% to 51%. One nephrectomy and seven
      pyeloplasties were performed and resolution of all patients' abdominal symptoms,
      including pain, resolved. CONCLUSIONS: Children with Dietl's crisis often suffer
      a delay in diagnosis; the clinical entity appears to be under-diagnosed. Renal
      parenchyma is typically preserved, and there is a paucity of associated urologic
      complaints. Once properly diagnosed, patients are well served by a pyeloplasty.
      Children with periumbilical pain and vomiting, particularly males, would benefit
      from ultrasound imaging.

PMID- 16953915
TI  - Circumcision revision in male children.
AB  - OBJECTIVE: To determine indications for circumcision revision and to identify the
      specialty of the person who performed unsatisfactory primary circumcision.
      MATERIALS AND METHODS: The authors reviewed medical records of 52 cases that
      underwent circumcision revision over a 6-year period (1998 to 2004). Sleeve
      surgical technique was used for revision in patients with redundant foreskin or
      concealed penis, penoplasty for partial or complete degloving of the penis and
      meatotomy for external meatal stenosis. The mean age of children was 32 months
      (range 6 months to 9 years). RESULTS: Most of unsatisfactory primary
      circumcisions (86.7%) were performed by laymen. All patients who underwent
      circumcision revision had good to excellent cosmetic results. CONCLUSION: Primary
      circumcision performed by laymen carry a high complication rate and serious
      complications may occur. A period of training and direct supervision by
      physicians is required before allowing laymen to perform circumcision
      independently.

PMID- 16953916
TI  - Female counterpart of shawl scrotum in Aarskog-Scott syndrome.
AB  - Aarskog-Scott syndrome (ASS) is an X-linked disorder characterized by facial,
      skeletal and genital anomalies, including penoscrotal transposition in males. We
      report on a girl from a family with ASS who exhibits a transposition of the
      clitoris.

PMID- 16953917
TI  - Pelvic floor exercises with biofeedback for stress urinary incontinence.
AB  - OBJECTIVE: Prospective study to objectively evaluate the benefits of pelvic floor
      strengthening exercises associated to biofeedback for the treatment of stress
      urinary incontinence. MATERIALS AND METHODS: Fourteen patients diagnosed with
      stress urinary incontinence (SUI) were selected for this study. All patients
      underwent a pelvic floor training associated to biofeedback for 12 consecutive
      weeks. Urodynamic tests, pad test and bladder diary were analyzed at the
      beginning of the study, at the end and after 3 months. The King's Health
      Questionnaire (KHQ) was applied before and after treatment to assess the impact
      in the quality of life. RESULTS: There was a significant reduction in the pad
      weight (from 14.21 g to 1 g), number of urinary leakage episodes (from 8.14 per
      day to 2.57 per day) and daytime frequency (from 7.93 per day to 5.85 per day).
      At urodynamics the authors observed a significant increase in Valsalva leak-point
      pressure (from 103.93 cm H2O to 139.14 cm H2O), cistometric capacity (from 249.29
      mL to 336.43 mL, p = 0.0015) and bladder volume at first desire to void (from 145
      mL to 215.71 mL). Those differences were kept during the first 3 months of follow
      up. The KHQ revealed significant differences except in the case of ''general
      health perception'', which covers health in general and not exclusively urinary
      incontinence. CONCLUSION: Treatment of SUI with pelvic floor exercises associated
      to biofeedback caused significant changes in the parameters analyzed, with
      maintenance of good results 3 months after treatment.

PMID- 16953918
TI  - Re: ultrasound guided percutaneous nephrostomy for obstructive uropathy in benign
      and malignant diseases.

PMID- 16953942
TI  - Interactions between respiratory syncytial virus and the host cell: opportunities
      for antivirus strategies?
AB  - At the start of the 21st century, respiratory syncytial virus (RSV) remains a
      serious global health concern. Although RSV has traditionally been acknowledged
      as a leading cause of morbidity and mortality in the paediatric population, the
      elderly and people with suppressed immune systems are now also recognised as
      being at risk from serious RSV infection. This problem is currently exacerbated
      by the lack of an effective vaccine to prevent RSV infection. Although the virus
      proteins play a variety of roles during the virus replication cycle, in many
      cases these tasks are performed via specific interactions with host-cell factors,
      including proteins, carbohydrates and lipids. The way in which RSV interacts with
      the host cell is currently being examined using a battery of different
      techniques, which encompass several scientific disciplines. This is providing new
      and interesting insights into how RSV interacts with the host cell at the
      molecular level, which in turn is offering the hope of new strategies to prevent
      RSV infection.

PMID- 16953943
TI  - Acute pulmonary hypertension causes depression of left ventricular contractility
      and relaxation.
AB  - BACKGROUND AND OBJECTIVE: The haemodynamic effects of acute pulmonary
      hypertension can be largely attributed to ventricular interdependence during
      diastole. However, there is evidence that the two ventricles also interact during
      systole. The aim of the present study was to examine the effects of acute
      pulmonary hypertension on both components of left ventricular systole, i.e.
      contraction and relaxation, using load-independent indices. METHODS: Ten pigs
      were instrumented with biventricular conductance catheters, a pulmonary artery
      flow probe and a high-fidelity pulmonary pressure catheter. Haemodynamic
      measurements were performed in baseline conditions and during stable pulmonary
      vasoconstriction induced by the thromboxane analogue U46619. Contractility was
      quantified using the end-systolic pressure-volume and preload recruitable stroke
      work relationships. The tau-end-systolic pressure relationship was used to assess
      load-dependency of relaxation. RESULTS: Acute pulmonary hypertension caused a
      decrease in the slope of the left ventricular preload recruitable stroke work
      relationship (from 6.64 +/- 1.7 to 5.19 +/- 1.9, mean +/- SD; P < 0.05), a
      rightward shift of the end-systolic pressure-volume relationship (P < 0.05), and
      an increase in the slope of the tau-end-systolic pressure relationship (from 
      0.15 +/- 0.5 to 0.35 +/- 0.17; P < 0.05). The diastolic chamber stiffness
      constant of both ventricles increased during pulmonary hypertension (P < 0.05).
      CONCLUSIONS: In the present model, acute pulmonary hypertension impairs left
      ventricular contractile function and relaxing properties. The present study
      provides additional evidence that, besides the well-known diastolic ventricular
      cross talk, systolic ventricular interaction may play a significant role in the
      haemodynamic consequences of acute pulmonary hypertension.

PMID- 16953944
TI  - Cardiac output measurements in off-pump coronary surgery: comparison between NICO
      and the Swan-Ganz catheter.
AB  - BACKGROUND: The aim of this prospective study was to compare continuous cardiac
      output measurements of the non-invasive cardiac output system (NICO) with the
      pulmonary artery catheter during off-pump coronary bypass surgery. METHODS:
      Twenty-two patients enrolled for off-pump coronary surgery received both a
      pulmonary artery catheter and a non-invasive cardiac output system for
      measurement of cardiac output. Data were compared by the Bland-Altman method to
      calculate the degree of agreement and to analyse if a significant difference
      existed between the two methods of cardiac output measurements. RESULTS:
      Perioperatively, the non-invasive cardiac output underestimated cardiac output,
      but postoperatively overestimated it. The limits of agreement were larger during
      surgery compared to the postoperative period (-3.1; +2.5 vs. -1.4; +2.2 L min(
      1)). Perioperatively, cardiac output measured with the pulmonary artery catheter
      varied from 0.5 to 7.5 L min(-1) (mean 3.6 L min(-1)) and with the non-invasive
      cardiac output from 0.5 to 8.4 L min(-1) (mean 3.9 L min(-1)). Postoperatively,
      these were 2.5-7.7 L min(-1) (mean 4.5 L min(-1)) and 2.3-8.4 L min(-1) (mean 4.9
      L min(-1)), respectively. CONCLUSION: During off-pump cardiac surgery, the non
      invasive cardiac output reliably measures cardiac output and does it more rapidly
      than a pulmonary artery catheter and may be more useful in order to detect rapid
      haemodynamic changes.

PMID- 16953945
TI  - Continuous cardiac output monitoring during haemodynamic changes in off-pump
      coronary artery bypass grafting surgery.

PMID- 16953946
TI  - A lack of toll-like receptor 4 expression variability in the immediate
      preoperative period: a pilot study of elective surgical patients.

PMID- 16953947
TI  - Thoracic epidural analgesia and antihypertensive therapy: a matter of timing?

PMID- 16953948
TI  - Hyponatraemic convulsions and fatal head injury secondary to desmopressin
      treatment for enuresis.

PMID- 16953949
TI  - Total spinal anaesthesia following epidural test dose in an ankylosing
      spondylitic patient with anticipated difficult airway undergoing total hip
      replacement.

PMID- 16953950
TI  - Short report: antimicrobial susceptibility and genetic characteristics of
      Haemophilus influenzae isolated from patients with respiratory tract infections
      between 1987 and 2000, including beta-lactamase-negative ampicillin-resistant
      strains.
AB  - The minimum inhibitory concentration (MIC) of five antibiotics and the presence
      of resistance genes was determined in 163 Haemophilus influenzae isolates
      collected over 13 years (1987-2000) in four two-yearly sampling periods from
      patients with respiratory tract infections. The prevalence of beta-lactamase
      negative ampicillin-susceptible strains was approximately 80% over the sampling
      period although fewer strains (65.9%) were recovered in the period 1995-1997. TEM
      1 type beta-lactamase-producing strains were less frequent starting at 15.6% and
      declining to 2.2% in the final sampling period. Low-beta-lactamase-negative
      ampicillin-resistant (BLNAR) strains were uncommon in 1987-1989 (2.2%), peaked to
      19.5% in 1995-1997, but fell back to 11.1% by 2000. Fully BLNAR strains were not
      detected until the last sampling period (6.7%). The MICs of ampicillin,
      levofloxacin, cefditoren and ceftriaxone remained stable but there was an eight
      fold increase in the MIC of cefdinir over the sampling period. Pulsed-field gel
      electrophoresis of DNA digests showed that three representative BLNAR strains
      were genetically distinct and 11 DNA profiles were identified among 17 low-BLNAR
      strains. These data suggest that the number of genetically altered BLNAR and low
      BLNAR strains are increasing in Japan.

PMID- 16953951
TI  - Hepatitis C virus: laboratory surveillance in England and Wales, 1992-2004.
AB  - Between 1992 and 2004, a total of 49,819 confirmed hepatitis C infections have
      been reported to the Health Protection Agency (HPA) by laboratories in England
      and Wales; the annual number of reports increased from 241 in 1991 to 8149 in
      2004. Most reports with a known risk factor were in injecting drug users (87%,
      12,438/14,221), but 71% (35,598/49,819) of the total had no reported identified
      risk. The age-sex distribution of the latter cases was similar to that in
      injecting drug users. Using names to assign ethnicity, individuals with South
      Asian names had an older age distribution and a different risk factor profile
      from non-South Asians. Using published age-specific prevalence data from 1996, it
      was estimated that around 28,1764 cases of hepatitis C infection exist in England
      and Wales, and that only 17% of these cases have been reported to the HPA.
      Surveillance reports continue to provide important information regarding trends
      in hepatitis C infection in specific risk groups.

PMID- 16953952
TI  - Preparedness for a smallpox outbreak: comparing metrics for assessing levels of
      vaccination among health-care workers by state.
AB  - By mid-2005, less than 17% of smallpox vaccine doses distributed to American
      states for health-care workers (HCWs) during the CDC campaign had been used. To
      understand how states responded, vaccination patterns were studied. Metrics were
      calculated to compare the level of preparedness for a smallpox outbreak in terms
      of absolute numbers of HCWs vaccinated compared to the percentage of doses
      distributed to each state, the rate of vaccination per capita population, and the
      percentage of HCWs vaccinated compared to the number the CDC recommended. States
      were then ranked. Results showed that rankings for all four metrics were
      statistically different (P<0.0001). In addition, when ranks were assigned to
      quartiles, the states directly affected on 9/11/01 ranked lowest and states
      widely perceived to be at lower terror risk ranked in the top. These results
      underscore the need to critically examine how to define an appropriate level of
      preparedness for a smallpox outbreak.

PMID- 16953953
TI  - Bayesian geostatistical prediction of the intensity of infection with Schistosoma
      mansoni in East Africa.
AB  - A Bayesian geostatistical model was developed to predict the intensity of
      infection with Schistosoma mansoni in East Africa. Epidemiological data from
      purpose-designed and standardized surveys were available for 31,458
      schoolchildren (90% aged between 6 and 16 years) from 459 locations across the
      region and used in combination with remote sensing environmental data to identify
      factors associated with spatial variation in infection patterns. The
      geostatistical model explicitly takes into account the highly aggregated
      distribution of parasite distributions by fitting a negative binomial
      distribution to the data and accounts for spatial correlation. Results identify
      the role of environmental risk factors in explaining geographical heterogeneity
      in infection intensity and show how these factors can be used to develop a
      predictive map. Such a map has important implications for schisosomiasis control
      programmes in the region.

PMID- 16953954
TI  - Prevalence and occurrence of stress urinary incontinence in elite women athletes.
AB  - OBJECTIVE: 1) To assess the prevalence of stress urinary incontinence (SUI) and
      urge urinary incontinence (UTI) in elite women athletes versus the general female
      population, and 2) to analyze the conditions of occurrence of urine loss in
      search of etiological clues in elite athletes. DECISION: An anonymous self
      questionnaire was collected transversally from women aged 18 to 35 years. The
      exposed group was composed of elite female athletes; the non-exposed group was
      made up of women in the same age range accepting to answer the questionnaire.
      RESULTS: A total of 157 answers from elite athletes and 426 from control subjects
      were available for analysis. Urinary incontinence prevalence was 28% for athletes
      and 9.8% for control subjects (p = .001). There was no significant difference in
      the relative prevalence of SUI between the athletes and control subjects.
      Athletes reported urine loss more frequently during the second part of the
      training session (p < 0.0003), and the second part of competition (p < 0.05).
      Urinary incontinence prevalence was 9.87% in physically-active control subjects
      versus 9.84% in sedentary control subjects (NS). Even a small quantity of urine
      loss was felt to be embarrassing. Most incontinent women did not dare to speak of
      their condition to anybody. CONCLUSIONS: There is a very high prevalence of
      urinary incontinence in women athletes. Detailed studies of the patho-physiology
      of this problem are necessary to formulate preventive recommendations.

PMID- 16953955
TI  - Expecting the best for students: teacher expectations and academic outcomes.
AB  - BACKGROUND: Research into teacher expectations has shown that these have an
      effect on student achievement. Some researchers have explored the impact of
      various student characteristics on teachers' expectations. One attribute of
      interest is ethnicity. AIMS: This study aimed to explore differences in teachers'
      expectations and judgments of student reading performance for Maori, Pacific
      Island, Asian and New Zealand European students. A further objective was to
      compare teacher expectations and judgments with actual student achievement.
      SAMPLE: The participants were 540 students of 21 primary teachers in Auckland
      schools. Of these students, 261 were New Zealand European, 88 were Maori, 97 were
      Pacific Island and 94 were Asian. METHODS: At the beginning of the year, the
      teachers completed a survey related to their expectations for their students'
      achievement in reading and, at the end of the year, they judged the reading
      levels their students had actually achieved. The survey data were compared with
      running record data. RESULTS: Teachers' expectations for students in reading were
      significantly higher than actual achievement for all ethnic groups other than
      Maori. Maori students' achievement was similar to that of the other groups at the
      beginning of the year but, by the end of the year, they had made the least gains
      of all groups. CONCLUSIONS: Sustaining expectation effects are one explanation
      for Maori students' limited progress. For Pacific Island, Asian and New Zealand
      European students, positive self-fulfilling prophecies may be operating. Future
      research could investigate the learning opportunities provided to these ethnic
      groups and the relationship of these to teachers' expectations.

PMID- 16953956
TI  - Factors related to perceived power usage in schools.
AB  - Based on Raven's (1992) power interaction model, situational and personal
      variables were examined as determinants of power choice in educational settings.
      The impact of educational sector (secular, religious), class level, gender and
      content of conflict on perceived power usage in teacher-pupil conflicts was
      analysed. A total of 370 elementary and junior high school pupils and 62 teachers
      from the same schools responded to a series of scenarios where they were asked
      how often specific power bases are used by teachers in trying to gain compliance.
      Results indicated that harsh power bases were perceived as more prevalent in the
      secular educational sector rather than in the religious one, in junior high
      school rather than elementary school, for boys as compared with girls, and for
      conflicts stemming from students rather than teachers. Findings were interpreted
      in terms of conformity level and frequency of conflicts. The discussion also
      addresses the lack of correspondence between teacher and pupil responses.

PMID- 16953957
TI  - Sex differences in cognitive abilities test scores: a UK national picture.
AB  - BACKGROUND AND AIMS: There is uncertainty about the extent or even existence of
      sex differences in the mean and variability of reasoning test scores ( Jensen,
      1998; Lynn, 1994, ; Mackintosh, 1996). This paper analyses the Cognitive
      Abilities Test (CAT) scores of a large and representative sample of UK pupils to
      determine the extent of any sex differences. SAMPLE: A nationally representative
      UK sample of over 320,000 school pupils aged 11-12 years was assessed on the CAT
      (third edition) between September 2001 and August 2003. The CAT includes separate
      nationally standardized tests for verbal, quantitative, and non-verbal reasoning.
      The size and recency of the sample is unprecedented in research on this issue.
      METHODS: The sheer size of the sample ensures that any sex difference will
      achieve statistical significance. Therefore, effect sizes (d) and variance ratios
      (VR) are employed to evaluate the magnitude of sex differences in mean scores and
      in score variability, respectively. RESULTS: The mean verbal reasoning score for
      girls was 2.2 standard score points higher than the mean for boys, but only 0.3
      standard points in favour of girls for non-verbal reasoning (NVR), and 0.7 points
      in favour of boys for quantitative reasoning (QR). However, for all three tests
      there were substantial sex differences in the standard deviation of scores, with
      greater variance among boys. Boys were over represented relative to girls at both
      the top and the bottom extremes for all tests, with the exception of the top 10%
      in verbal reasoning. CONCLUSIONS: Given the small differences in means,
      explanations for sex differences in wider domains such examination attainment at
      age 16 need to look beyond conceptions of 'ability'. Boys tend to be both the
      lowest and the highest performers in terms of their reasoning abilities, which
      warns against the danger of stereotyping boys as low achievers.

PMID- 16953958
TI  - Season of birth and childhood intelligence: findings from the Aberdeen Children
      of the 1950s cohort study.
AB  - BACKGROUND: In this study, 2 main hypotheses have been put forward to explain the
      variation in childhood intelligence or school performance by season of birth. In
      the first hypothesis, it is suggested that it is due to school policy concerning
      school entry, whereas the second suggests that a seasonally patterned exposure
      such as temperature, maternal nutrition, or infection during critical periods of
      brain development have a lasting effect on intelligence. AIMS: To determine
      whether childhood performance on tests of different domains of intelligence is
      patterned by season of birth and to examine possible mechanisms for any
      associations. SAMPLE: 12,150 individuals born in Aberdeen, Scotland between 1950
      and 1956. METHODS: Birth cohort study in which the variation in different domains
      of childhood intelligence measured at ages 7, 9, and 11 by season of birth were
      examined. RESULTS: Reading ability at age 9 and arithmetic ability at age 11
      varied by season of birth, with lowest scores among those born in autumn or early
      winter (September-December) and highest scores among those born in later winter
      or spring (February-April); p=.002 for joint sine-cosine functions for reading
      ability at age 9 and p=.05 for sine-cosine function for arithmetic ability at age
      11. The child's perception and understanding of pictorial differences at age 7,
      verbal reasoning at 11, and English language ability at 11 did not vary by season
      of birth. Age at starting primary school and age relative to class peers were
      both associated with the different measurements of childhood intelligence and
      both attenuated the association between month of birth and reading ability at age
      9 and arithmetic ability at age 11 towards the null. Both adjusted and unadjusted
      differences in reading ability at age 9 and arithmetic ability at age 11 between
      those born from September to December compared with other times of the year were
      less than 0.1 of a standard deviation of the test scores. Ambient temperature
      around the time of conception, during gestation, and around the time of birth did
      not affect intelligence. CONCLUSION: Any variation in mean childhood intelligence
      by season of birth is weak and largely explained by age at school entry and age
      relative to class peers.

PMID- 16953959
TI  - Book reading styles in dual-parent and single-mother families.
AB  - BACKGROUND: Whereas many studies have investigated quantitative aspects of book
      reading (frequency), few have examined qualitative aspects, especially in very
      young children and through direct observations of shared reading. AIM: The
      purpose of this study was to determine possible differences in book-reading
      styles between mothers and fathers and between mothers from single- and dual
      parent families. It also related types of parental verbalizations during book
      reading to children's reported language measures. SAMPLE: Dual-parent (29) and
      single-parent (24) families were observed in shared book reading with their
      toddlers (15-month-olds) or young preschoolers (27-month-olds). METHOD: Parent
      child dyads were videotaped while book reading. The initiator of each book
      reading episode was coded. Parents' verbalizations were exhaustively coded into
      10 categories. Mothers completed the MacArthur Communicative Development
      Inventory, and the children were given the Bayley scales. RESULTS: All parents
      differentiated their verbalizations according to the age rather than the gender
      of the child, but single mothers imitated female children more than males. Few
      differences in verbalizations were found between mothers and fathers or between
      mothers from single- and dual-parent families. Fathers allowed younger children
      to initiate book-reading episodes more than mothers. For both age groups of
      children, combined across families, verbalizations that related the book to the
      child's experience were correlated with reported language measures. Questions and
      imitations were related to language measures for the older age group.
      CONCLUSIONS: The important types of parental verbalizations during shared book
      reading for children's language acquisition are relating, questions and
      imitations.

PMID- 16953960
TI  - The role of learning to read in the development of problem behaviour: a cross
      lagged longitudinal study.
AB  - BACKGROUND: This study investigates the posited relationship between learning to
      read, and internalizing and externalizing problem behaviours, during the
      transition from preschool to primary school. METHODS: A total of 196 (104 boys,
      92 girls) children participating in the Jyvaskyla Entrance into Primary School
      (JEPS) study were followed up six times during their transition from preschool to
      primary school. At each measurement, the children's reading performance was
      tested. Moreover, their internalizing and externalizing problem behaviour was
      examined by means of structured interviews. RESULTS: The results showed that
      problems in reading acquisition predicted an increase in internalizing problem
      behaviour during the preschool year and first grade, whereas during the second
      grade they were associated with an increase in subsequent externalizing problem
      behaviour. Moreover, from preschool to the beginning of the primary school
      internalizing problem behaviour predicted subsequent externalizing problem
      behaviour. Later on during the first and the second primary school years, it was
      externalizing problem behaviour that predicted an increase in internalizing
      problem behaviour. CONCLUSIONS: The results of this study suggested that
      difficulties in learning to read, and internalizing and externalizing problem
      behaviours are developmentally linked in a cumulative manner.

PMID- 16953961
TI  - Influences on cognitive engagement: epistemological beliefs and need for closure.
AB  - BACKGROUND: Research indicates that achievement goals influence cognitive
      engagement, which, in turn, influences academic achievement. We believe that
      there are other individual difference variables in the realm of personal
      epistemology that may also directly or indirectly influence cognitive engagement;
      specifically, epistemological beliefs and epistemological motives (e.g. need for
      closure). AIMS: This study proposed and tested a conceptual model of
      relationships among epistemological variables (epistemological beliefs and need
      for closure), achievement goals (mastery, performance-approach, performance
      avoidance) and cognitive engagement. SAMPLE: Two hundred and fifty-nine students
      attending university in the US volunteered to participate in the study. Students
      represented a variety of academic disciplines and ranged from 18 to 58 years.
      METHODS: The participants completed three paper-and-pencil surveys: the
      Epistemological Beliefs Inventory; the Attitudes, Beliefs, and Experiences
      Inventory (a measure of need for closure); and the Approaches to Learning Survey
      (a measure of achievement goals and cognitive engagement). RESULTS: Structural
      equation modelling supported the model in general, although not all proposed
      paths were significant. Correlational analyses further indicated that
      epistemological beliefs and need for closure are both potentially important
      variables for understanding learners' treatment of knowledge in instructional
      settings. CONCLUSIONS: There are individual differences in epistemological
      beliefs and motives that may influence the goals students pursue in learning
      settings and the nature of their cognitive engagement.

PMID- 16953962
TI  - Teachers' and pupils' definitions of bullying.
AB  - BACKGROUND: Comparison of teachers' and pupils' definitions of bullying is
      important for considering the implications for reports of its incidence in
      schools, for the study of developmental trends in children's and adolescents'
      perceptions of the phenomenon and for evaluating the effectiveness of
      interventions designed to combat bullying. AIMS: To investigate the effects of
      gender, teacher/pupil status and, for pupils, bullied/non-bullied (target/non
      target) status and age on the definition of bullying. SAMPLES: Teachers (N=225:
      158 women, 67 men) and pupils (N=1,820: 466 boys, 460 girls were 11-12 years old,
      year 7, and 415 boys, 479 girls were 13-14 years, year 9) in 51 UK secondary
      schools participated in a questionnaire survey. A total of 557 of the pupils (117
      girls and 117 boys aged 11-12 years, and 197 girls and 126 boys aged 13-14 years)
      reported that they had been bullied at some time in their present school.
      METHODS: Written questionnaire responses to the question, 'Say what you think
      bullying is' have been content analysed to derive two sets of categories, one of
      bullying behaviour and the other of effects of bullying on the target. RESULTS:
      Regarding both bullying behaviour and the effects of bullying on the target,
      teachers - by comparison with pupils - have been found to express more
      comprehensive ideas in their definitions. Specifically, pupils compared with
      teachers are more likely to restrict their definitions to direct bullying (verbal
      and/or physical abuse) and are less likely to refer to social exclusion, a power
      imbalance in the bully's favour and the bully's intention to cause the target
      hurt or harm and to feel threatened. Analysis of definitions on the bases of sex,
      pupil age and target/non-target status show that: targets are more likely than
      non-targets are to refer to the bully's physically and verbally abusive
      behaviour, and for Year 7 compared with Year 9 pupils, to suggest that bullies
      socially exclude targets; girls are more likely than boys are to mention verbal
      abuse and the effects on the target of 'Feels hurt/harm', but boys are more
      likely than girls are to construe bullying as involving repetition; older pupils
      are more likely than younger ones are to refer to a power imbalance in the
      bully's favour but, for bully targets, younger ones compared with older ones are
      more likely to invoke the idea of social exclusion in their definitions.
      CONCLUSIONS: The most important implication of the findings of this study that
      there are important differences between teachers' and pupils' definitions of
      bullying is that teachers need to listen carefully to what pupils have to say
      about bullying and work with and help them to develop their conceptions of the
      phenomenon. Some teachers, too, need to develop their conceptions of bullying.

PMID- 16953963
TI  - Peer victimization and depression in early-mid adolescence: a longitudinal study.
AB  - BACKGROUND: Despite considerable evidence for psychological distress among
      children and young people who experience peer victimization, cross-sectional
      studies cannot determine the direction of the relationship. Several recent
      studies have examined associations between victimization and distress. The
      majority find evidence for both directions but do not arbitrate between them;
      only one prior study has attempted to do this. AIMS: To use longitudinal data to:
      (1) test competing hypotheses about the direction of the victimization-depression
      association; (2) investigate gender differences in the resulting models. SAMPLE:
      Data were obtained from a Scottish school-based cohort (N=2,586). METHODS: Self
      completion questionnaires included a depression scale and questions on
      victimization at each age. RESULTS: Despite shifts in and out of victim status,
      there was evidence of stability in both victimization and depression. Bivariate
      analyses showed positive relationships between victimization and depression.
      Structural equation modelling (SEM) showed that at age 13, this relationship was
      reciprocal, with a stronger path from victimization to depression than vice
      versa. However, at age 15, it was almost entirely due to a path from depression
      to victimization among boys. Models including cross-lagged paths fitted the data
      less well than those including simultaneous associations. CONCLUSIONS: Current
      policy focuses on victimization as a cause of distress; however, professionals
      should be aware that vulnerable children and young people are likely to be the
      targets of victimization.

PMID- 16953964
TI  - Are mastery and ability goals both adaptive? Evaluation, initial goal
      construction and the quality of task engagement.
AB  - AIMS: The aims of this research were to examine the predictions that (a) the kind
      of evaluation pupils anticipate will influence their initial achievement goals
      and, as a result, the quality and consequences of task engagement; and (b)
      initial mastery goals will promote new learning and intrinsic motivation and
      initial ability goals will promote entity beliefs that ability is fixed. SAMPLE:
      Participants were 312 secondary school pupils at ages 13-15. METHODS: Pupils
      expected to receive normative evaluation, temporal evaluation (scores over time)
      or no evaluation. Mastery and ability goals were measured before pupils worked on
      challenging problems; intrinsic motivation and entity beliefs were measured after
      task completion. RESULTS: Anticipation of temporal evaluation enhanced initial
      mastery goals, anticipation of normative evaluation enhanced ability goals and
      the no-evaluation condition undermined both. Anticipation of temporal evaluation
      enhanced new learning (strategy acquisition and performance gains) and intrinsic
      motivation both directly and by enhancing initial mastery goals; anticipation of
      normative evaluation enhanced entity beliefs by enhancing ability goals.
      CONCLUSIONS: Results confirmed that evaluation conveys potent cues as to the
      goals of activity. They also challenged claims that both mastery and ability
      goals can be adaptive by demonstrating that these were differentially associated
      with positive versus negative processes and outcomes. Results have theoretical
      and applied implications for understanding and improving evaluative practices and
      student motivation.

PMID- 16953965
TI  - Effects of cueing and collaboration on the acquisition of complex legal skills.
AB  - BACKGROUND: To overcome the teacher bandwidth problem in supporting large groups
      of students, both automated process support (cueing) and face-to-face feedback by
      peers during small group work (collaboration) can be provided to students. AIM:
      The purpose of this experimental study was to examine whether a multimedia
      practical containing cueing could be effectively combined with peer feedback to
      support the acquisition of the complex skill of preparing a plea in court.
      SAMPLE: In the context of a regular court practical, 50 junior law students at a
      Dutch university individually studied a multimedia practical and participated in
      small group discussions about intermediate learning outcomes of the practical.
      METHOD: The study examined the effects of cueing and collaboration on training
      outcomes and transfer pleas, and on cognitive activity during collaboration, by
      combining the multimedia practical and small group collaboration to support the
      complex task of preparing a plea in court. RESULTS: Both cueing and collaboration
      positively influence training outcomes, with participants without cueing
      benefiting most from additional collaboration. Transfer plea scores reveal a
      positive effect of collaboration but a negative effect of cueing. Analysis of
      discussions during small group collaboration reveals a negative effect of cueing
      on the level of cognitive activity. CONCLUSION: Peer feedback during small group
      work indeed appears to be a feasible option to be combined with or (partially)
      substitute individualized cueing when training complex learning tasks.

PMID- 16953966
TI  - The Approaches to Teaching Inventory: a critique of its development and
      applicability.
AB  - BACKGROUND: The Approaches to Teaching Inventory (ATI) is structured as two main
      scales, reflecting a teacher-centred information-transmission approach versus a
      student-centred conceptual-change approach, each subdivided into intention and
      strategy subscales. Its use in higher education investigations is increasing and,
      by default, it is assuming an operational definition of variation in 'approaches
      to teaching'. However, the ATI's conceptual foundations and procedures of
      development have not been systematically scrutinized. AIMS: The present paper
      presents a comprehensive historical review and critique of the ATI's development.
      METHOD: The procedures applied in the ATI's initial development are critically
      evaluated. Close attention is paid to the source of its foundation item pool, the
      criteria used in selecting from those foundation items, the adequacy of subject
      samples used in item trialling and the uses made of resultant trial response data
      in determining the final form of the inventory. The historical record is examined
      closely to determine the conceptual and psychometric credibility of the
      instrument. CONCLUSIONS: There are serious and irreversible concerns with the
      rigour and methodology adopted in the psychometric development of the ATI. The
      ATI manifestly does not reflect a functionally useful range of 'approaches to
      teaching', and its application to activities connected with the
      professionalization (and evaluation) of university teaching is rejected.

PMID- 16953967
TI  - An assessment of anxiety levels in dyslexic students in higher education.
AB  - BACKGROUND: It has long been hypothesized that children with learning
      disabilities, including dyslexia, may be highly vulnerable to emotional
      consequences such as anxiety. However, research has centred on school-aged
      children. AIMS: The present study aimed to clarify these findings with dyslexic
      students in higher education. SAMPLES: Sixteen students with dyslexia were
      compared with 16 students with no history of learning difficulties. METHODS:
      Students were asked to complete a written questionnaire concerning trait anxiety
      levels. They were then told that they would be given a timed reading test and
      their state anxiety levels were measured using the State-Trait Anxiety Inventory
      (STAI; Spielberger, Gorsuch, & Lushene, 1983). Finally, their reading was
      assessed using the Test of Word Reading Efficiency (TOWRE; Torgesen, Wagner, &
      Rashotte, 1999). RESULTS: Dyslexic students showed slower reading speeds than
      controls. They also had higher levels of state anxiety and elevated levels of
      academic and social, but not appearance, anxiety. CONCLUSIONS: Dyslexic students
      in higher education show anxiety levels that are well above what is shown by
      students without learning difficulties. This anxiety is not limited to academic
      tasks but extends to many social situations. It is proposed that assessment of
      emotional well-being should form part of the assessment of need for dyslexic
      students entering higher education.

PMID- 16953968
TI  - Comparing groups in a before-after design: when t test and ANCOVA produce
      different results.
AB  - BACKGROUND: Researchers often test people before and after some treatment and
      compare these scores with a control group. Sometimes it is not possible to
      allocate people into conditions randomly, which means the initial scores for the
      two groups may differ. There are two main approaches: t test on the gain scores
      and ANCOVA partialling out the initial scores. Lord (1967) showed that these can
      lead to different conclusions. This is an often-discussed paradox in psychology
      and education. AIMS: The reasons why these approaches can lead to different
      conclusions, the assumptions that each approach makes and how the approaches
      relate to group allocation, are discussed Methods. Three sets of simulations are
      reported that investigate the relationships among effect size, group allocation,
      measurement error and Lord's paradox. CONCLUSIONS: Recommendations are given that
      stress careful examination of the research questions, sampling and allocation of
      participants and graphing the data. ANCOVA is appropriate when allocation is
      based on the initial scores, t test can be appropriate if allocation is
      associated non-causally with the initial scores, but often neither approach
      provides adequate results.

PMID- 16953972
TI  - Roles for accessory molecules in microbial recognition by Toll-like receptors.
AB  - The Toll family of receptors recognizes a variety of microbial products and
      triggers immune responses. Recent progress has revealed a requirement for
      accessory molecules in microbial recognition by Toll-like receptors.
      Lipopolysaccharide (LPS) recognition requires LPS binding protein (LBP), CD14,
      and MD-2. MD-2 is directly involved in ligand-binding and subsequent receptor
      activation, whereas LBP and CD14 control ligand presentation to the receptor
      complex, Toll-like receptor (TLR4)/MD-2. CD14 and LBP influence the amplitude of
      LPS responses and LPS-induced type I interferon production. TLR2 is also reported
      to require similar accessory molecules. Innate immune responses to microbial
      products driven by TLRs are controlled by accessory molecules working upstream of
      TLRs.

PMID- 16953973
TI  - Diversity of endotoxin and its impact on pathogenesis.
AB  - Lipopolysaccharide or LPS is localized to the outer leaflet of the outer membrane
      and serves as the major surface component of the bacterial cell envelope. This
      remarkable glycolipid is essential for virtually all Gram-negative organisms and
      represents one of the conserved microbial structures responsible for activation
      of the innate immune system. For these reasons, the structure, function, and
      biosynthesis of LPS has been an area of intense research. The LPS of a number of
      bacteria is composed of three distinct regions--lipid A, a short core
      oligosaccharide, and the O-antigen polysaccharide. The lipid A domain, also known
      as endotoxin, anchors the molecule in the outer membrane and is the bioactive
      component recognized by TLR4 during human infection. Overall, the biochemical
      synthesis of lipid A is a highly conserved process; however, investigation of the
      lipid A structures of various organisms shows an impressive amount of diversity.
      These differences can be attributed to the action of latent enzymes that modify
      the canonical lipid A molecule. Variation of the lipid A domain of LPS serves as
      one strategy utilized by Gram-negative bacteria to promote survival by providing
      resistance to components of the innate immune system and helping to evade
      recognition by TLR4. This review summarizes the biochemical machinery required
      for the production of diverse lipid A structures of human pathogens and how
      structural modification of endotoxin impacts pathogenesis.

PMID- 16953974
TI  - Lipopolysaccharide-induced proliferation and adhesion of U937 cells to
      endothelial cells involves barium chloride sensitive hyperpolarization.
AB  - The adhesion of monocytes to the endothelium and their proliferation in the
      subendothelial space play an important role in atherosclerosis. Since the
      proliferation and migration of cells are influenced by the activity of ion
      channels, the aim of this study was to examine whether barium chloride (Ba(2+))
      sensitive potassium channels (K(iCa)) are involved in lipopolysaccharide (LPS)
      induced proliferation of monocytic U937 cells, and in the adhesion of these cells
      to endothelial cells. The adhesion of LPS-stimulated U937 cells to endothelial
      cells reached a maximum at a concentration of 5 microg/ml. This effect of LPS was
      completely abolished in the presence of Ba(2+) (100 micromol/l). In addition, LPS
      induced proliferation was significantly reduced by Ba(2+) (control, 100%; LPS 5
      microg/ml, 175%; LPS + Ba(2+) 100 micromol/l, 136%; n = 12, P < 0.05). To examine
      whether K(iCa) are activated by LPS, changes of U937 membrane potential were
      determined. LPS (5 microg/ml) caused a hyperpolarization of U937 cells indicating
      a flux of K(+) ions out of the cells. This effect was completely blocked by
      Ba(2+) (100 micromol/l). In conclusion, we demonstrate that LPS activates K(iCa)
      in U937 cells, which is responsible for LPS-induced adhesion of these cells to
      endothelial cells, and to the proliferation of U937 cells.

PMID- 16953975
TI  - TLR2- and TLR4-dependent activation of STAT1 serine phosphorylation in murine
      macrophages is protein kinase C-delta-independent.
AB  - Engagement of Toll-like receptor (TLR) proteins activates multiple signal
      transduction pathways. Previous studies demonstrated that TLR2 and TLR4
      engagement leads to rapid phosphorylation of the transcription factor STAT1 at
      serine 727 (Ser-727 STAT1) in murine macrophages. Only TLR4 engagement induced
      STAT1 phosphorylation at tyrosine 701, although this response was delayed
      compared with Ser-727 STAT1 phosphorylation. Unlike other cell types, the p38
      mitogen-activated protein kinase was necessary, but not sufficient, for TLR
      induced phosphorylation of Ser-727 STAT1 in macrophages. We and others had
      previously shown that Ser-727 STAT1 phosphorylation could be blocked by
      rottlerin, an inhibitor of protein kinase C-delta (PKC-delta). Here we report
      that peritoneal exudate macrophages from PKC-delta-deficient mice can be
      activated through TLR2 and TLR4 to elicit rapid phosphorylation of Ser-727 STAT1,
      which was blocked by both rottlerin and the p38 inhibitor SB203580, but not by
      the pan-PKC inhibitor bisindoylmaleamide. Furthermore, both normal and PKC-delta
      deficient macrophages secreted comparable amounts of IL-6, IP-10, and RANTES
      following TLR engagement. In contrast, IFN-gamma-induced STAT1 serine
      phosphorylation was independent of both PKC-delta and p38. Overall, these studies
      demonstrate that a PKC-delta-independent signaling pathway downstream of both
      TLR2 and TLR4 is necessary for Ser-727 STAT1 phosphorylation in primary murine
      macrophages.

PMID- 16953976
TI  - beta-Glucans in standardized allergen extracts.
AB  - BACKGROUND: Allergen extracts contain variable quantities of bacterial endotoxin.
      Recent studies have suggested that (1-->3)-beta-D-glucans (beta-glucans), also
      microbial cell wall components, may have adjuvant properties that could affect
      allergen immunotherapy. OBJECTIVE: To determine the quantities of beta-glucans in
      standardized allergen extracts. MATERIALS AND METHODS: Ninety-four lots of 13
      standardized allergen extracts were tested for beta-glucan content by Glucatell
      assay, and for endotoxin content by a specific, chromogenic formulation of the
      Limulus amebocyte lysate test. RESULTS: Standardized allergen extracts contain
      variable quantities of endotoxins and beta-glucans. As in our previous work,
      endotoxin activity was greatest in cat pelt and Dermatophagoides farinae, and
      least in the pollens. There was no correlation between endotoxin and beta-glucan
      levels (r = 0.1887; P = 0.07). beta-Glucan content was highest for grass pollen
      (median content, 10.6 ng/ml; range, 0.4-41.8 ng/ml), ragweed pollen (32.9 ng/ml;
      range, 6.5-41.2 ng/ml), and cat pelt (25.5 ng/ml; range, 16.7-41.1 ng/ml), and
      lowest for cat hair (4.9 ng/ml; range, 1.2-10.3 ng/ml), D. farinae (1.2 ng/ml;
      range, 0.4-5.2 ng/ml) and Dermatophagoides pteronyssinus (1.8 ng/ml; range, 0.4
      6.7 ng/ml). CONCLUSIONS: beta-Glucans are present in standardized allergen
      extracts. The effects of these quantities of beta-glucans on allergen
      immunotherapy and allergen skin testing require further study.

PMID- 16953977
TI  - The interferon response to bacterial and viral infections.
AB  - Type I interferons (IFNs) were first described several decades ago as soluble
      factors that were capable of 'interfering' with viral replication when added to
      infected cells. Type I IFNs have been shown to be induced by recognition of viral
      DNA and RNA via three distinct pathways: (i) a TRIF-dependent pathway in
      macrophages via TLRs 3 and 4; (ii) a MyD88-dependent pathway in plasmacytoid
      dendritic cells (pDCs) via TLRs 7/8 and 9; and (iii) an intracellular recognition
      pathway utilizing the cytoplasmic receptors RIG-I/MDA5. Interestingly, these
      viral recognition pathways converge on TRAF3, which induces interferon through
      the activation of IRF3 or IRF7 by the TBK-1 and IKKi complexes. While type I IFN
      has been traditionally associated with antiviral responses, recent studies have
      demonstrated that many bacteria also induce type I interferon responses. The
      mechanisms of type I IFN induction and its role in host defense, however, are
      largely unclear. Studies with the Gram-positive intracellular bacterium Listeria
      monocytogenes indicated that it may trigger type I IFN induction through novel
      TLR-independent intracellular receptors and type I IFN may play a detrimental
      role to host response against listerial infection. In this article, we summarize
      some of these findings and discuss the functional differences of type I IFNs in
      bacterial and viral infections.

PMID- 16953978
TI  - NALP3: a key player in caspase-1 activation.
AB  - The NLR (NACHT-LRR) family of proteins have been implicated in the regulation of
      immune responses and cell death pathways. Some NLR family members can form
      multiprotein complexes, called inflammasomes, involved in the activation of pro
      inflammatory caspases. Mutations in the NALP3/CIAS1/cryopyrin gene, a member of
      the NLR family, are linked to three auto-inflammatory disorders: Muckle-Wells
      syndrome, familial cold auto-inflammatory syndrome and neonatal-onset multisystem
      inflammatory disease. NALP3 along with the adaptor molecule ASC activates caspase
      1 in response to a wide variety of stimuli. Here we review recent findings on the
      biology of NALP3 suggesting that it has functions beyond that of pathogen
      recognition.

PMID- 16953981
TI  - Healthy mental ageing.
AB  - Healthy mental ageing may be defined as the absence of the common disabling
      mental health problems of older people, especially cognitive decline and
      depression, accompanied by the perception of a positive quality of life. Older
      people are particularly prone to negative effects on mental health due to poor
      physical health. Modifiable aspects of lifestyle have been shown to be associated
      with healthy mental ageing. These include increased physical activity,
      intellectual stimulation (including education), avoidance of smoking and various
      aspects of diet. There is reasonably strong evidence that the treatment of
      hypertension will decrease the risk of cognitive impairment, and moderate alcohol
      intake may also have some benefits on cognition. These modifiable lifestyle
      factors may benefit from deliberate individual and population health promotion
      strategies to maximize mental health in old age, although to date intervention
      trials have not been performed to support the evidence obtained from
      observational studies.

PMID- 16953982
TI  - Adjuvant aromatase inhibitors and bone health.
AB  - Adjuvant hormonal therapy results in substantial improvements in disease-free and
      overall survival for women with operable breast cancer. Use of an aromatase
      inhibitor (AI) is expected to replace tamoxifen as standard care for many
      patients. Aromatase is the enzyme responsible for the final step in estrogen
      biosynthesis. This is the conversion of the androgens testosterone and
      androstenedione to the estrogens estrone and estradiol. AIs are potent inhibitors
      of estrogen production and thus one of the major concerns over their use is their
      effect on bone health and their potential to increase the incidence of
      osteoporosis and risk of fracture. The American Society of Clinical Oncology has
      recognized that these patients are at high risk of developing osteoporosis and
      has published guidelines to aid in their management. These recommend that all
      patients have an initial dual-energy X-ray absorptiometry (DEXA) bone scan to
      assess bone mineral density and are offered calcium and vitamin D supplements as
      well as lifestyle advice. Patients with osteoporosis should be treated with a
      bisphosphonate to reduce the incidence of fracture. Osteonecrosis of the jaws is
      a recently described adverse side-effect of bisphosphonate therapy and has been
      described in women with metastatic breast cancer. Oversuppression of bone
      turnover is probably the primary mechanism for the development of this condition.
      The degree of risk for osteonecrosis with bisphosphonates is uncertain and
      warrants careful monitoring.

PMID- 16953983
TI  - Migraine and the menopause.
AB  - The prevalence of migraine peaks during the 40s and an increased association
      between migraine and menstruation is often noted. Migraine generally improves
      after the menopause. Although menstrual irregularity, hot flushes and other
      climacteric symptoms may warrant management with hormone replacement therapy
      (HRT), there has been some concern that HRT may aggravate migraine and
      potentially increase the risk of ischaemic stroke. This evidence-based review
      concludes that migraine is not a contraindication for HRT but continuous-release
      transdermal estrogen, in the lowest effective dose, is recommended.

PMID- 16953984
TI  - Non-surgical treatment for detrusor overactivity.
AB  - Urinary incontinence is a common but under-reported condition. Approximately 17%
      of women are affected by detrusor overactivity at some time in their lives.
      Pharmacological treatment of this condition used to be severely limited by the
      side-effects of the drugs and the associated poor patient compliance. Recently,
      however, the tolerability and effectiveness of pharmacotherapy have been improved
      by the introduction of new drugs and alternative methods of drug delivery. This
      review assesses the effectiveness and tolerability of these new treatments.
      Anticholinergic agents, botulinum toxin and neuromodulation are also discussed.

PMID- 16953985
TI  - A 10-year follow-up of postmenopausal women on long-term continuous combined
      hormone replacement therapy: Update of safety and quality-of-life findings.
AB  - OBJECTIVE: To assess the safety and health-related quality of life (HRQOL) of
      continuous combined hormone replacement therapy (ccHRT) with estradiol
      valerate/medroxyprogesterone acetate (E(2)V/MPA) over nine years and at follow-up
      one year after discontinuation. STUDY DESIGN: A total of 419 women were
      randomized to one of four treatments: once-daily 1 mg E2V/2.5 mg MPA (1 + 2.5
      group); 1 mg E2V/5 mg MPA daily (1 + 5 group); 2 mg E2V/2.5 mg MPA daily (2 + 2.5
      group); 2 mg E2V/5 mg MPA daily (2 + 5 group) (Indivina, Orion Pharma). For the
      last six months, all received the 1 + 2.5 dosage. The 2 + 2.5 dosage was
      discontinued at the end of year 7. A total of 198 women continued after year 7.
      RESULTS: Annualized percentage rates for cardiovascular events [corrected] and
      endometrial cancers [corrected] were below national rates for Finland and those
      reported for the Women's Health Initiative. There were no serious events with the
      1 + 2.5 dosage or after ccHRT discontinuation. Climacteric symptoms remained
      significantly below baseline values after dosage reduction; some symptoms
      recurred after discontinuation of ccHRT. HRQOL ratings improved with ccHRT,
      irrespective of dosage, including depressed mood, anxiety, health perception and
      sexual interest. Scores on a scale assessing daily functioning and enjoyment (Q
      LES-Q) improved from year 7 to year 9. They deteriorated during follow-up in
      women not continuing ccHRT. CONCLUSIONS: Lower dosages of HRT were as effective
      as higher doses in improving climacteric symptoms and HRQOL ratings and had fewer
      safety concerns. Following discontinuation of ccHRT, patient satisfaction was
      variable, with 15% electing to continue or restart HRT and 7% resuming at follow
      up. This supports the need for an individualized approach to therapy
      recommendations.

PMID- 16953986
TI  - Exercise for women in the early postmenopausal years.
AB  - Exercise has many benefits throughout life but in later life in particular it
      will protect against cardiovascular disease, obesity, diabetes and cancer, and
      preserve musculoskeletal health and psychological wellbeing. Women as they get
      older are at increasing risk of osteoporosis and the aim of exercise is to slow
      these skeletal changes. The early postmenopausal years in particular are
      associated with a rapid loss of bone mass, together with a loss of aerobic
      fitness and muscle strength. Therefore an evidence-based exercise regime to
      protect against these problems is essential, so that the exercise is of the
      appropriate quantity, duration and intensity for the required outcome.

PMID- 16953987
TI  - The importance of peer review.

PMID- 16953988
TI  - Upfront.

PMID- 16953989
TI  - Oral malodor: a review of the literature.
AB  - Oral malodor or halitosis is any unpleasant odor emerging from the mouth that is
      detected by others. Many patients experience extreme discomfort and embarrassment
      and therefore seek help for this problem. Oral causes, such as poor oral hygiene,
      periodontal disease, tongue coating, food impaction, unclean dentures, faulty
      restorations, and dry mouth, are far more common than nonoral causes of malodor.
      Management may include simple measures such as scaling and root planing,
      instructions in oral hygiene, tongue cleaning, and mouth rinsing. This paper
      reviews the current knowledge, etiology, diagnosis, and possible treatment
      strategies for oral malodor. Emphasis is placed on the recognition of the dental
      hygienist as a specialist in aspects of patient care and instruction, which
      relate to the prevention and control of oral malodor.

PMID- 16953990
TI  - Effects of daily oral care with 0.12% chlorhexidine gluconate and a standard oral
      care protocol on the development of nosocomial pneumonia in intubated patients: a
      pilot study.
AB  - PURPOSE: The purpose of this pilot study was to determine if a difference existed
      between nosocomial pneumonia rates for intubated critical care unit (CCU)
      patients who received twice-daily oral hygiene care with 0.12% chlorhexidine
      gluconate and those who received the standard oral care. METHODS: Over seven
      months (February to August), CCU patients were identified through screening and
      informed consent procedures, and randomized into 1 of 2 groups. Over the 7
      months, due to the critically ill nature of the patients, only 5 subjects were
      enrolled. While in the study, twice-daily oral hygiene care consisted of brushing
      the cheeks, teeth, and endotracheal tube with a suctioning toothbrush using an
      FDA-approved 0.12% chlorhexidine gluconate antimicrobial agent with the
      experimental group (2 intubated patients in the CCU). The control group (3
      intubated patients in the CCU) received the standard oral care 6 times per day
      utilizing a soft foam swab and half strength hydrogen peroxide. All oral care was
      performed by the nursing staff. The number of persons developing nosocomial
      pneumonia was monitored until hospital discharge. RESULTS: Results revealed that
      1 person out of 3 in the control group was discharged from the hospital with a
      diagnosis of nosocomial (aspiration) pneumonia. Neither of the 2 subjects in the
      experimental group was diagnosed with nosocomial pneumonia. Preliminary findings
      suggest that twice-daily oral hygiene care with 0.12% chlorhexidine gluconate may
      reduce the risk of nosocomial pneumonia in intubated patients more than the 6
      times daily standard oral care protocol. The standard oral care protocol does not
      include the use of an FDA-approved antimicrobial solution. However, the small
      size of the sample makes this finding inconclusive. CONCLUSION: Twice-daily oral
      hygiene care with 0.12% chlorhexidine gluconate may hold promise as a nosocomial
      pneumonia reduction strategy within hospital CCUs; however, its application
      requires further testing.

PMID- 16953991
TI  - Bisphosphonate-associated osteonecrosis of the jaw: a literature review and
      clinical practice guidelines.
AB  - BACKGROUND: Osteonecrosis of the jaw has recently been reported as a possible
      adverse drug effect from bisphosphonate therapy. Reports are coming from all over
      the world. Norvartis, a pharmaceutical manufacturer of two implicated drug
      products, has notified dentists in the United States and made recommendations for
      dental management of cases. MECHANISM OF ACTION: The exact mechanism of
      bisphosphonate effects leading to osteonecrosis of the jaw is unknown. The
      condition can affect both the maxilla and the mandible. Most cases developed
      following oral infection or dental treatment. PREVENTION AND MANAGEMENT: Clinical
      guidelines for prevention and management have recently been published. Dental
      hygienists have a major role in patient education related to awareness of the
      potential drug effect and to preventive oral health education.

PMID- 16953993
TI  - CMO's report on revalidation.

PMID- 16953994
TI  - Can early diagnosis and effective management combat the irresistible rise of
      COPD?

PMID- 16953995
TI  - Obesity and the overworked GP.

PMID- 16953996
TI  - Incidence and determinants of moderate COPD (GOLD II) in male smokers aged 40-65
      years: 5-year follow up.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major health
      problem with an estimated prevalence of 10-15% among smokers. The incidence of
      moderate COPD, as defined by the Global Initiative for Chronic Obstructive Lung
      Disease (GOLD), is largely unknown. AIM: To determine the cumulative incidence of
      moderate COPD (forced expiratory volume in 1 second/forced vital capacity ratio
      [FEV1/FVC] <0.7 and FEV1 <80% predicted) and its association with patient
      characteristics in a cohort of male smokers. DESIGN: Prospective cohort study.
      SETTING: The city of IJsselstein, a small town in the Netherlands. METHOD:
      Smokers aged 40-65 years who were registered with local GPs, participated in a
      study to identify undetected COPD. Baseline measurements were taken in 1998 of
      399 smokers with normal spirometry (n = 292) or mild COPD (FEV1/FVC <0.7 and FEV1
      >or=80% predicted, n = 107) and follow-up measurements were conducted in 2003.
      RESULTS: After a mean follow-up of 5.2 years, 33 participants developed moderate
      COPD (GOLD II). This showed an estimated cumulative incidence of 8.3% (95% CI =
      5.8 to 11.4) and a mean annual incidence of 1.6%. No participant developed severe
      airflow obstruction. The risk of developing moderate COPD in smokers with
      baseline mild COPD (GOLD I) was five times higher than in those with baseline
      normal spirometry (one in five versus one in 25). CONCLUSIONS: In a cohort of
      middle-aged male smokers, the estimated cumulative incidence of moderate COPD
      (GOLD II) over 5 years was relatively high (8.3%). Age, childhood smoking, cough,
      and one or more GP contacts for lower respiratory tract problems were
      independently associated with incident moderate COPD.

PMID- 16953997
TI  - Antibiotics and steroids for exacerbations of COPD in primary care: compliance
      with Dutch guidelines.
AB  - BACKGROUND: The Dutch College of General Practitioners' guidelines specify that
      antibiotics should only be used for severe cases of chronic obstructive pulmonary
      disease (COPD). However, GPs tend to administer antibiotics rather than a short
      course of steroid treatment regardless of severity. AIM: The aim of this study
      was to determine how GPs use current guidelines in treating exacerbations of
      COPD, in particular whether short courses of oral steroids and antibiotics are
      prescribed in accordance with the Dutch guidelines for COPD. DESIGN OF STUDY:
      Retrospective analysis of medical records. SETTING: Primary healthcare centres.
      METHOD: Medical records of patients registered at four primary healthcare centres
      in the Netherlands were retrospectively analysed for the period March 2001-March
      2003. RESULTS: Of 35,589 patients, 1.3% were registered as having a diagnosis of
      COPD. In 2 years, 47% of the patients had no exacerbation, 35% had one or two
      exacerbations, and 18% had three or more exacerbations. Of 536 exacerbations, GPs
      prescribed a short course of oral steroids in 30% of cases, antibiotics in 29%,
      steroids combined with an antibiotic in 23%, and no oral steroid course or
      antibiotic was prescribed in 18%. Prescriptions for patients with three or more
      exacerbations differed significantly from those for patients with one or two
      exacerbations. CONCLUSIONS: Treatment is often not in accordance with current
      guidelines; in particular, antibiotics are prescribed more often than
      recommended.

PMID- 16953998
TI  - Primary care support for tackling obesity: a qualitative study of the perceptions
      of obese patients.
AB  - BACKGROUND: Obesity has become a major public health issue and there is concern
      about the response of health services to patients who are obese. The perceptions
      of obese patients using primary care services have not been studied in depth.
      AIM: To explore obese patients' experiences and perceptions of support in primary
      care. DESIGN OF STUDY: Qualitative study with semi-structured interviews
      conducted in participants' homes. SETTING: Five general practices contrasting in
      socioeconomic populations in Sheffield. METHOD: Purposive sampling and semi
      structured interviewing of 28 patients with a diverse range of ages, backgrounds,
      levels of obesity and experiences of primary care services. RESULTS: Participants
      typically felt reluctance when presenting with concerns about weight and
      ambivalence about the services received. They also perceived there to be
      ambivalence and a lack of resources on the part of the health services.
      Participants showed a strong sense of personal responsibility about their
      condition and stigma-related cognitions were common. These contributed to their
      ambivalence about using services and their sensitivity to its features. Good
      relationships with primary care professionals and more intensive support partly
      ameliorated these effects. CONCLUSION: The challenges of improving access to and
      quality of primary care support in tackling obesity are made more complex by
      patients' ambivalence and other effects of the stigma associated with obesity.

PMID- 16953999
TI  - Conducting randomised controlled trials in primary care: lessons from an obesity
      management trial.
AB  - BACKGROUND: A UK trial ending in 2002 reported that a training intervention to
      improve the management of obesity in primary care had no impact. Process analysis
      showed that the intervention was taken up by very few of the practitioners in the
      participating practices. AIM: The aim of the current study was to explore both
      the reasons behind low levels of implementation and the context in which the
      trial was delivered. DESIGN: In-depth qualitative interviews. SETTING: General
      practices in the North East of England. METHOD: Interviews with 13 practitioners
      (GPs and practice nurses) and 10 patients, representing seven of the eight
      intervention practices in the largest centre of the original trial. RESULTS:
      While patients were clear that they had participated in a trial few of those
      interviewed had any recollection of the intervention. Most staff were positive
      about the training, resources to use with patients and the weight management
      model, but not all training needs were met. High initial expectations of the
      trial gave way to disillusionment, exacerbated by significant misunderstanding by
      some practice staff of their role in implementation. CONCLUSIONS: Frustration
      among practitioners managing obesity in primary care combined with unrealistic
      expectations of and misunderstanding about an intervention designed to improve
      care in the field, appeared to have resulted in disillusionment with and
      consequent disengagement from the trial.

PMID- 16954000
TI  - A population-based study of different antibiotic prescribing in different areas.
AB  - BACKGROUND: Respiratory tract infections are the most common reason for
      antibiotic prescription in Sweden as in other countries. The prescription rates
      vary markedly in different countries, counties and municipalities. The reasons
      for these variations in prescription rate are not obvious. AIM: To find possible
      explanations for different antibiotic prescription rates in children. DESIGN OF
      STUDY: Prospective population based study. SETTING: All child health clinics in
      four municipalities in Sweden which, according to official statistics, had high
      antibiotic prescription rates, and all child health clinics in three
      municipalities which had low antibiotic prescription rates. METHOD: During one
      month, parents recorded all infectious symptoms, physician consultations and
      antibiotic treatments, from 848 18-month-old children in a log book. The parents
      also answered a questionnaire about socioeconomic factors and concern about
      infectious diseases. RESULTS: Antibiotics were prescribed to 11.6% of the
      children in the high prescription area and 4.7% in the low prescription area
      during the study month (crude odds ratio [OR] = 2.67; 95% confidence interval
      [CI] = 1.45 to 4.93). After multiple logistic regression analyses taking account
      of socioeconomic factors, concern about infectious illness, number of symptom
      days and physician consultations, differences in antibiotic prescription rates
      remained (adjusted OR = 2.61; 95% CI = 1.14 to 5.98). The variable that impacted
      most on antibiotic prescription rates, although it was not relevant to the
      geographical differences, was a high level of concern about infectious illness in
      the family. CONCLUSIONS: The differences in antibiotic prescription rates could
      not be explained by socioeconomic factors, concern about infectious illness,
      number of symptom days and physician consultations. The differences may be
      attributable to different prescription behaviour.

PMID- 16954001
TI  - Antibiotic-resistant infections in primary care are symptomatic for longer and
      increase workload: outcomes for patients with E. coli UTIs.
AB  - BACKGROUND: Antimicrobial resistance is considered to be one of the major threats
      to public health. However, the practical implications for patients and workload
      in primary care are largely unknown. AIM: To determine outcomes for patients
      managed in primary care with an antibiotic resistant compared to an antibiotic
      sensitive Escherichia coli (E. coli) urinary tract infection (UTI). DESIGN:
      Nested case control study with prospective measurement of outcomes. SETTING: Ten
      general practices in South Wales. METHOD: Patients consulting with symptoms
      suggestive of UTI identified through systematic sampling, and with a laboratory
      proven E. coli infection, were followed up by interview 1 month after their
      consultations and by searching of their medical records. RESULTS: Nine hundred
      and thirty-two patients were interviewed and had their medical records reviewed.
      The risk of patients reporting 'feeling poorly', 'frequency or pain on urinating'
      and being 'out of action' for more than 5 days after consulting was significantly
      increased for patients with resistant compared to sensitive infections. After
      adjusting for risk factors, there was an increased risk of 'frequency or pain on
      urinating' and 'being out of action' for those infected with a resistant E. coli.
      The median number of maximum reported days with at least one symptom was 12 days
      for patients with E. coli infections resistant to trimethoprim, 7 days for
      infections resistant to ampicillin, 7 days for infections resistant to any
      antibiotic, and 5 days for infections sensitive to all tested antibiotics. Even
      if treated with an appropriate antibiotic, infections caused by a resistant
      strain were symptomatic for longer. For those infected with an organism resistant
      to at least one antibiotic, the odds ratio (OR) for re-visiting their GP within
      the next 30 days for the UTI was 1.47 (95% confidence interval [CI] = 1.10 to
      1.95). The OR was 1.49 (95% CI = 1.11 to 2.00) for ampicillin resistance and 2.48
      (95% CI = 1.70 to 3.59) for trimethoprim resistance. CONCLUSIONS: Resistant E.
      coli UTIs are symptomatic for longer and cause increased work load in general
      practice.

PMID- 16954002
TI  - Deep vein thrombosis in primary care: possible malignancy?
AB  - BACKGROUND: The increased prevalence of unrecognised malignancy in patients with
      deep vein thrombosis (DVT) has been well established in secondary care settings.
      However, data from primary care settings, needed to tailor the diagnostic workup,
      are lacking. AIM: To quantify the prevalence of unrecognised malignancy in
      primary care patients who have been diagnosed with DVT. DESIGN: Prospective
      follow-up study. SETTING: All primary care physicians affiliated/associated with
      a non-teaching hospital in a geographically circumscribed region participated in
      the study. METHOD: A total of 430 consecutive patients without known malignancy,
      but with proven DVT were included in the study and compared with a control group
      of 442 primary care patients, matched according to age and sex. Previously
      unrecognised, occult malignancy was considered present if a new malignancy was
      diagnosed within 2 years following DVT diagnosis (DVT group) or inclusion in the
      control group. Patients with DVT were categorised in to those with unprovoked
      idiopathic DVT and those with risk factors for DVT (that is, secondary DVT).
      RESULTS: During the 2-year follow-up period, a new malignancy was diagnosed 3.6
      times more often in patients with idiopathic DVT than in the control group (2
      year incidence: 7.4% and 2.0%, respectively). The incidence in patients with
      secondary DVT was 2.6%; only slightly higher than in control patients.
      CONCLUSION: Unrecognised malignancies are more common in both primary and
      secondary care patients with DVT than in the general population. In particular,
      patients with idiopathic DVT are at risk and they could benefit from
      individualised case-finding to detect malignancy.

PMID- 16954003
TI  - The safety and adequacy of antithrombotic therapy for atrial fibrillation: a
      regional cohort study.
AB  - BACKGROUND: Atrial fibrillation is a common problem in older people. The evidence
      base for the safety of warfarin and aspirin in atrial fibrillation is largely
      derived from selective research studies and secondary care. Further assessment of
      the safety of warfarin in older people with atrial fibrillation in routine
      primary care is needed. AIM: To measure the complication rates and adequacy of
      warfarin control in a cohort of patients with atrial fibrillation managed in
      primary care and compare them with published data from controlled trials and
      community patients with atrial fibrillation not receiving warfarin. DESIGN OF
      STUDY: Retrospective review of regional cohort. SETTING: Twenty-seven general
      practices in southwest Scotland. METHOD: Case note review of 601 patients
      previously identified as having atrial fibrillation by GPs. RESULTS: The average
      age of our cohort was 77 years at recruitment. Two hundred and sixty-four (44%)
      patients died within 5 years of follow up. Three hundred and nine of the 601
      (51%) patients with atrial fibrillation took warfarin at some stage during this
      study. INR (international normalised ratio) was maintained between 2 and 3 for
      68% of the time. Bleeding risk was higher in patients taking warfarin than in
      those on aspirin or no antithrombotic therapy (warfarin 9.0% per year versus
      aspirin 4.7% per year versus no therapy 4.6% per year). The annual risk of any
      bleeding complication on warfarin (9%) was similar to that recorded in randomised
      trials (9.2%) whereas the annual risk of severe bleeding was approximately double
      (2.6 versus 1.3%). CONCLUSION: Adequacy of anticoagulant control was broadly
      comparable to that reported in clinical trials, whereas the risk of severe
      bleeding was higher, possibly reflecting the older age and the comorbidities of
      our unselected cohort.

PMID- 16954004
TI  - Values-based practice in primary care: easing the tensions between individual
      values, ethical principles and best evidence.
AB  - BACKGROUND: The provision of health care is inseparable from universal values
      such as caring, helping and compassion. Consideration for individual values,
      particularly those of the patient, has also been increasing. However, such
      consideration is difficult within the context of modern health care, where
      complex and conflicting values are often in play. This is particularly so when a
      patient's values seem to be at odds with evidence-based practice or widely shared
      ethical principles, or when a health professional's personal values may
      compromise the care provided. SUGGESTED NEW FRAMEWORK: Values-based practice, a
      framework developed originally in the domain of mental health, maintains that
      values are pervasive and powerful parameters influencing decisions about health,
      clinical practice and research, and that their impact is often underestimated.
      Although it shares starting points with other approaches to values, it suggests
      that our current approaches lead us to ignore some important manifestations of
      values at both the general level, as relevant in legal, policy and research
      contexts, as well as at the individual level, as relevant in clinical practice.
      Drawing on ideas from philosophy, values-based practice significantly extends the
      range of phenomena that may be regarded as value-laden. It suggests that one of
      the reasons for overlooking values is that they are presumed to be shared when
      not apparently conflicting. Values-based practice is an approach to supporting
      clinical decision-making, which provides practical skills and tools for eliciting
      individual values and negotiating these with respect to best available evidence.

PMID- 16954005
TI  - The heart of the matter: the case for taking childhood obesity seriously.

PMID- 16954006
TI  - Comparing costs.

PMID- 16954007
TI  - Influenza vaccine.

PMID- 16954011
TI  - Problem-based learning: how do the outcomes compare with traditional teaching?

PMID- 16954012
TI  - Health care in secure environments.

PMID- 16954013
TI  - On madness: a personal account of rapid cycling bipolar disorder.

PMID- 16954014
TI  - A miscalculation of sublime dimensions.

PMID- 16954017
TI  - Clinical Trials Report.

PMID- 16954016
TI  - An ostrich contemplates PBC.

PMID- 16954018
TI  - Light emission requires exposure to the atmosphere in ex vivo bioluminescence
      imaging.
AB  - The identification of organs bearing luciferase activity by in vivo
      bioluminescence imaging (BLI) is often difficult, and ex vivo imaging of excised
      organs plays a complementary role. This study investigated the importance of
      exposure to the atmosphere in ex vivo BLI. Mice were inoculated with murine pro-B
      cell line Ba/F3 transduced with firefly luciferase and p190 BCR-ABL. They were
      killed following in vivo BLI, and whole-body imaging was done after death and
      then after intraperitoneal air injection. In addition, the right knee was exposed
      and imaged before and after the adjacent bones were cut. Extensive light signals
      were seen on in vivo imaging. The luminescence disappeared after the animal was
      killed, and air injection restored the light emission from the abdomen only,
      suggesting a critical role of atmospheric oxygen in luminescence after death.
      Although no substantial light signal at the right knee was seen before bone
      cutting, light emission was evident after cutting. In conclusion, in ex vivo BLI,
      light emission requires exposure to the atmosphere. Bone destruction is required
      to demonstrate luciferase activity in the bone marrow after death.

PMID- 16954019
TI  - In vivo testing of Renilla luciferase substrate analogs in an orthotopic murine
      model of human glioblastoma.
AB  - In vivo bioluminescent imaging using cells expressing Renilla luciferase is
      becoming increasingly common. Hindrances to the more widespread use of Renilla
      luciferase are the high autoluminescence of its natural substrate,
      coelenterazine, in plasma, the relatively high absorbance by tissue of the light
      emitted by the enzyme-substrate reaction; rapid clearance of the substrate; and
      significant cost. These factors, save for the cost, which has its own limiting
      effect on use, can combine to reduce the sensitivity of in vivo assays utilizing
      this reporter system, and methods of increasing light output or decreasing
      autoluminescence could be of great benefit. A number of analogs of coelenterazine
      are being investigated may accomplish one or both of these goals. In this study
      that we report on the testing of two new substrate analogs, EnduRen and ViViren,
      manufactured by Promega Corporation, in an orthotopic murine model of human
      glioblastoma expressing Renilla luciferase. We have tested these analogs in this
      cell line both in vitro and in vivo, and find that the substrate viviren results
      in significantly greater light output than the natural substrate or the other
      analog EnduRen. This new substrate could be valuable for studies where greater
      sensitivity is important.

PMID- 16954020
TI  - In vivo monitoring of pancreatic beta-cells in a transgenic mouse model.
AB  - We generated a transgenic mouse model (RIP-luc) for the in vivo monitoring of
      pancreatic islet mass and function in response to metabolic disease. Using the
      rat insulin promoter fused to firefly luciferase, and noninvasive technology to
      detect luciferase activity, we tracked changes in reporter signal during
      metabolic disease states and correlated the changes in luciferase signal with
      metabolic status of the mouse. Transgene expression was found to be specific to
      the pancreatic islets in this transgenic model. Basal transgene expression was
      tracked in male and female mice fed either a chow or a high-fat diet and in
      response to treatment with streptozotocin. Pancreatic bioluminescent signal
      increased in mice fed a high-fat diet compared with chow-fed animals. In a model
      of chemically induced diabetes, the bioluminescent signal decreased in accordance
      with the onset of diabetes and reduction of islet beta-cell number. Preliminary
      studies using islets transplanted from this transgenic model suggest that in vivo
      image analysis can also be used to monitor transplanted islet viability and
      survival in the host. This transgenic model is a useful tool for in vivo studies
      of pancreatic beta-cells and as a donor for islet transplantation studies.

PMID- 16954021
TI  - Bioluminescent monitoring of NIS-mediated (131)I ablative effects in MCF-7
      xenografts.
AB  - Optical imaging has made it possible to monitor response to anticancer therapies
      in tumor xenografts. The concept of treating breast cancers with (131)I is
      predicated on the expression of the Na(+)/I- symporter (NIS) in many tumors and
      uptake of I- in some. The pattern of (131)I radioablative effects were
      investigated in an MCF-7 xenograft model dually transfected with firefly
      luciferase and NIS genes. On Day 16 after tumor cell implantation, 3 mCi of
      (131)I was injected. Bioluminescent imaging using d-luciferin and a cooled charge
      coupled device camera was carried out on Days 1, 2, 3, 7, 10, 16, 22, 29, and 35.
      Tumor bioluminescence decreased in (131)I-treated tumors after Day 3 and reached
      a nadir on Day 22. Conversely, bioluminescence steadily increased in controls and
      was 3.85-fold higher than in treated tumors on Day 22. Bioluminescence in (131)I
      treated tumors increased after Day 22, corresponding to tumor regrowth. By Day
      35, treated tumors were smaller and accumulated 33% less (99m)TcO(4)(-) than
      untreated tumors. NIS immunoreactivity was present in <50% of (131)I-treated
      cells compared to 85-90% of controls. In summary, a pattern of tumor regression
      occurring over the first three weeks after (131)I administration was observed in
      NIS-expressing breast cancer xenografts.

PMID- 16954022
TI  - Cellular imaging of inflammation in atherosclerosis using magnetofluorescent
      nanomaterials.
AB  - OBJECTIVE: Magnetofluorescent nanoparticles (MFNPs) offer the ability to image
      cellular inflammation in vivo. To better understand their cellular targeting and
      imaging capabilities in atherosclerosis, we investigated prototypical dextran
      coated near-infrared fluorescent MFNPs in the apolipoprotein E-deficient (apo E-/
      ) mouse model. METHODS AND RESULTS: In vitro MFNP uptake was highest in activated
      murine macrophages (p < .001). Apo E-/- mice (n = 11) were next injected with the
      MFNP (15 mg/kg iron) or saline. In vivo magnetic resonance imaging (MRI)
      demonstrated strong plaque enhancement by the MFNPs (p < .001 vs. saline), which
      was confirmed by multimodality ex vivo MRI and fluorescence reflectance imaging.
      On fluorescence microscopy, MFNPs were found in cellular-rich areas of atheroma
      and colocalized with immunofluorescent macrophages over endothelial cells and
      smooth muscle cells (p < .001). CONCLUSIONS: Here we show that (1) the in vitro
      and in vivo cellular distribution of atherosclerosis-targeted MFNPs can be
      quantified by using fluorescence imaging methods; (2) in atherosclerosis,
      dextranated MFNPs preferentially target macrophages; and (3) MFNP deposition in
      murine atheroma can be noninvasively detected by in vivo MRI. This study thus
      provides a foundation for using MFNPs to image genetic and/or pharmacological
      perturbations of cellular inflammation in experimental atherosclerosis and for
      the future development of novel targeted nanomaterials for atherosclerosis.

PMID- 16954023
TI  - Feasibility and limits of magnetically labeling primary cultured rat T cells with
      ferumoxides coupled with commonly used transfection agents.
AB  - Visualization and quantification of inflammatory processes is of high importance
      for early diagnosis of a multitude of diseases. Magnetic resonance imaging (MRI)
      using iron oxide (FeO) nanoparticles as contrast agents allows the study of
      macrophage infiltration during inflammation in a variety of tissues. Macrophages
      are effectors of the immune response, their appearance being orchestrated by
      activated T lymphocytes. Therefore, tracking of labeled T lymphocytes, which
      initiate the immune process, should enable earlier detection of tissue
      inflammation. In this study, we investigate the feasibility of specifically
      labeling harvested T cells by using dextran-coated FeO nanoparticles and commonly
      available transfection agents (TAs). Physicochemical properties of the newly
      formed FeO/TA vesicles were determined as well as their cell toxicity and their T
      cell activation potential. The labeling efficiency of each FeO/TA combination was
      evaluated by measuring the transverse MRI relaxation rate R(2) by X-ray
      spectroscopy and magnetic selection. Toxicity and labeling efficacy differed
      significantly among TAs. The best results were achieved by using polyamine TAs
      and in particular by using poly-l-lysine at a concentration of 1.5 microg/mL
      administered in combination with 22.5 microg iron/mL. By using this protocol, up
      to 60% of harvested T cells could be labeled. Microscopic investigation revealed
      FeO/TA nanoparticles not only localized within the cytoplasma of the cells but
      also sticking to the outer membrane surface.

PMID- 16954024
TI  - Microimaging characterization of a B16-F10 melanoma metastasis mouse model.
AB  - Metastatic mouse models of melanoma have been characterized by gross necropsy
      examination, histopathology, and optical imaging. To determine if the time
      progression, extent, and metabolism of melanoma metastases could be monitored
      noninvasively, serial micro-CT and small-animal PET imaging studies were
      performed by using a mouse model of melanoma. Juvenile female C57BL/6 mice were
      injected intravenously with syngenic B16-F10 melanoma cells. Serial micro-CT
      imaging studies were performed on anesthetized mice. Mice were necropsied at the
      development of adverse clinical signs or at postinjection Day 30, and tissues
      were collected for histopathology. In a separate study of four mice, tumor
      viability was assessed with 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) and
      studied by using small-animal PET imaging. A total of 59% of the mice developed
      metastatic tumors. Micro-CT image analysis was able to identify and follow up to
      36% of metastatic lesions. Examples of metastatic lesions identified and followed
      up by micro-CT imaging included a lung metastasis, mandibular metastasis,
      subcutaneous metastasis, and tibial/femoral metastasis. Micro-CT and small-animal
      PET fusion imaging successfully correlated anatomic localization of glucose
      metabolism of the metastatic tumors. Micro-CT and small-animal PET imaging were
      found to be highly effective in detection and characterization of lesions
      produced by this metastatic melanoma model.

PMID- 16954026
TI  - "Clickable" nanoparticles for targeted imaging.
AB  - Nanomaterials functionalized with targeting ligands are increasingly recognized
      as useful materials for molecular imaging and drug delivery. Here we describe the
      development and validation of azide-alkyne reactions ("click chemistry") for the
      rapid, site-specific modification of nanoparticles with small molecules. The
      facile preparation of stable nanoparticles bearing azido or alkyne groups capable
      of reaction with their corresponding counterpart functionalized small molecules
      is demonstrated. The Cu(I)-catalyzed cycloaddition of azides and alkynes is shown
      to be a highly efficient and selective method for point functionalization of
      magnetic nanoparticles. Derivatized nanoparticles bearing biotin, fluorochrome,
      or steroid moieties are stable for several months. Nanoparticle click chemistry
      will be useful for other nanomaterials, design of novel sensors, and drug
      delivery vehicles.

PMID- 16954025
TI  - Assessment of cardiovascular apoptosis in the isolated rat heart by magnetic
      resonance molecular imaging.
AB  - Apoptosis, an active process of cell self-destruction, is associated with
      myocardial ischemia. The redistribution of phosphatidylserine (PS) from the inner
      to the outer leaflet of the cell membrane is an early event in apoptosis. Annexin
      V, a protein with high specificity and tight binding to PS, was used to identify
      and localize apoptosis in the ischemic heart.Fluorescein-labeled annexin V has
      been used routinely for the assessment of apoptosis in vitro. For the detection
      of apoptosis in vivo, positron emission tomography and single-photon emission
      computed tomography have been shown to be suitable tools. In view of the
      relatively low spatial resolution of nuclear imaging techniques, we developed a
      high-resolution contrast-enhanced magnetic resonance imaging (MRI) method that
      allows rapid and noninvasive monitoring of apoptosis in intact organs. Instead of
      employing superparamagnetic iron oxide particles linked to annexin V, a new T1
      contrast agent was used. To this effect, annexin V was linked to gadolinium
      diethylenetriamine pentaacetate (Gd-DTPA)-coated liposomes. The left coronary
      artery of perfused isolated rat hearts was ligated for 30 min followed by
      reperfusion. T(1) and T(2)* images were acquired by using an 11.7-T magnet before
      and after intracoronary injection of Gd-DTP-labeled annexin V to visualize
      apoptotic cells. A significant increase in signal intensity was visible in those
      regions containing cardiomyocytes in the early stage of apoptosis. Because
      labeling of early apoptotic cell death in intact organs by histological and
      immunohistochemical methods remains challenging, the use of Gd-DTPA-labeled
      annexin V in MRI is clearly an improvement in rapid targeting of apoptotic cells
      in the ischemic and reperfused myocardium.

PMID- 16954027
TI  - Imaging of proteolytic activity using a conditional cell surface receptor.
AB  - Programmed cell death (apoptosis) is a ubiquitous means utilized by multicellular
      organisms for elimination of unwanted cells during development and homeostasis.
      Dysregulated apoptosis is implicated in an array of clinical disorders including
      cancer, autoimmune diseases, neurodegenerative disorders, and ischemia. During
      programmed cell death, a series of proteases, known as caspases, with different
      specificities play crucial roles in the apoptotic process. Caspase-3, a group II
      cysteine aspartate protease, recognizes and cleaves substrates harboring the
      amino acid sequence aspartic acid-glutamic acid-valine-aspartic acid (DEVD), and
      it plays an important role in the terminal phase of apoptosis. Here we report the
      development of a novel imaging platform for sensing the activation of cellular
      proteases. A recombinant chimeric protein was constructed, composed of a cell
      surface-targeted single-chain antibody (sFv) fused to a Golgi retention signal.
      The DEVD tetrapeptide sequence was included between the single-chain antibody and
      the Golgi retention signal as a caspase-3 protease cleavage site. When expressed
      in cultured cells this fusion protein was localized to Golgi bodies and was not
      detected on the cell surface. Induction of apoptosis resulted in cleavage of the
      fusion protein releasing the single-chain antibody from the Golgi retention
      signal in a caspase-dependent manner. As a result, in cells undergoing apoptosis
      the single-chain antibody was visualized at the cell surface by
      immunofluorescence microscopy. The expression of sFv on the surface of cells in a
      protease-dependent manner provides a unique opportunity for real-time imaging
      through the use of targeted nanoparticles. This methodology may provide for a
      multimodal noninvasive real-time imaging of apoptosis and a new opportunity for
      high-throughput screening of cell-death-modulating therapeutic agents.

PMID- 16954028
TI  - Ultrasound radiation force modulates ligand availability on targeted contrast
      agents.
AB  - Radiation force produced by low-amplitude ultrasound at clinically relevant
      frequencies remotely translates freely flowing microbubble ultrasound contrast
      agents over distances up to centimeters from the luminal space to the vessel wall
      in order to enhance ligand-receptor contact in targeting applications. The
      question arises as to how the microbubble shell might be designed at the
      molecular level to fully take advantage of such physical forces in targeted
      adhesion for molecular imaging and controlled therapeutic release. Herein, we
      report on a novel surface architecture in which the tethered ligand is buried in
      a polymeric overbrush. Our results, with biotin-avidin as the model ligand
      receptor pair, show that the overbrush conceals the ligand, thereby reducing
      immune cell binding and increasing circulation persistence. Targeted adhesion is
      achieved through application of ultrasound radiation force to instantly reveal
      the ligand within a well-defined focal zone and simultaneously bind the ligand
      and receptor. Our data illustrate how the adhesive properties of the contrast
      agent surface can be reversibly changed, from stealth to sticky, through the
      physical effects of ultrasound. This technique can be combined with any ligand
      receptor pair to optimize targeted adhesion for ultrasonic molecular imaging.

PMID- 16954029
TI  - Chloroquine treatment increases detection of 5-fluorouracil-induced apoptosis
      index in vivo.
AB  - Although apoptosis can be readily assessed in vitro with a variety of techniques,
      the detection of apoptosis in the in vivo setting poses a much more difficult
      proposition. Apoptosis in an organism is followed almost inevitably by rapid
      clearance of dying cells via phagocytosis, thus limiting the ability to analyze
      apoptosis in vivo using classical techniques. To address this issue, we developed
      a method to enhance in vivo apoptosis detection using pretreatment with
      chloroquine, an inhibitor of macrophage activity, in Swiss albino mice. This
      technique resulted in a significant increase in the accumulation of apoptotic
      cells induced by 5-fluorouracil, as detected by propidium iodide staining in
      solid and ascitic forms of Ehrlich ascitic tumors and in bone marrow cells. We
      further validated our technique using DNA fragmentation and endonuclease assays.
      Our results demonstrated that chloroquine pretreatment can significantly enhance
      accumulation of apoptotic cells in organisms, and we envision combining this
      method with modern imaging techniques to optimize in vivo detection of apoptosis.

PMID- 16954030
TI  - Normalized transillumination of fluorescent proteins in small animals.
AB  - We investigated the capacity of normalized transillumination methods in imaging
      fluorescent proteins in visible light, in phantoms and in live mice. We
      demonstrate significant imaging improvements over epi-illumination imaging, as
      commonly applied today. Of particular importance is the significant betterment in
      contrast achieved, due to minimization of the influence of autofluorescence and
      the enhancement of depth sensitivity compared to epi-illumination imaging.
      Although normalized transillumination does not match the accuracy and
      quantification capacity of tomographic imaging, it nevertheless attains key
      advantages over other planar optical imaging methods while preserving
      implementation simplicity. Due to the balance achieved between simplicity and
      accuracy, normalized transillumination approaches could serve as an important
      alternative molecular imaging method.

PMID- 16954032
TI  - Reduction of image artifacts in mice by bladder flushing with a novel double
      lumen urethral catheter.
AB  - In electron paramagnetic resonance imaging (EPRI), the accumulation of contrast
      agent in the bladder can create a very large source of signal, often far greater
      than that of the organ of interest. Mouse model images have become increasingly
      important in preclinical testing. To minimize bladder accumulation on mouse
      images, we developed a novel, minimally invasive, MRI/EPRI-friendly procedure for
      flushing a female mouse bladder. It is also applicable to other imaging
      techniques, for example, PET, SPECT, etc., where contrast agent accumulation in
      the bladder is also undesirable. A double-lumen urethral catheter was developed,
      using a standard IV catheter with a silicone tube extension, having a
      polyethylene tube threaded into the IV catheter. Flushing of the bladder provides
      a substantial reduction in artifacts, as shown in images of tumors in mice.

PMID- 16954031
TI  - Application of ultrasound to selectively localize nanodroplets for targeted
      imaging and therapy.
AB  - Lipid-coated perfluorocarbon nanodroplets are submicrometer-diameter liquid
      filled droplets with proposed applications in molecularly targeted therapeutics
      and ultrasound (US) imaging. Ultrasonic molecular imaging is unique in that the
      optimal application of these agents depends not only on the surface chemistry,
      but also on the applied US field, which can increase receptor-ligand binding and
      membrane fusion. Theory and experiments are combined to demonstrate the
      displacement of perfluorocarbon nanoparticles in the direction of US propagation,
      where a traveling US wave with a peak pressure on the order of megapascals and
      frequency in the megahertz range produces a particle translational velocity that
      is proportional to acoustic intensity and increases with increasing center
      frequency. Within a vessel with a diameter on the order of hundreds of
      micrometers or larger, particle velocity on the order of hundreds of micrometers
      per second is produced and the dominant mechanism for droplet displacement is
      shown to be bulk fluid streaming. A model for radiation force displacement of
      particles is developed and demonstrates that effective particle displacement
      should be feasible in the microvasculature. In a flowing system, acoustic
      manipulation of targeted droplets increases droplet retention. Additionally, we
      demonstrate the feasibility of US-enhanced particle internalization and
      therapeutic delivery.

PMID- 16954033
TI  - Noninvasive near-infrared imaging of fluorochromes within the brain of live mice:
      an in vivo phantom study.
AB  - Near-infrared fluorescence (NIRF) imaging has great potential for studying
      physiological and pathophysiological processes noninvasively in several locations
      of the body. In this study, we evaluated the feasibility of NIRF imaging to
      visualize fluorescent compounds within the brains of live mice commonly used in
      brain research. To simulate the presence of a molecular NIRF reporter agent at
      the site of a lesion, we developed a new in vivo phantom model wherein capsules
      containing different amounts of an NIRF dye (Cy5.5) were stereotactically
      implanted deep into the left hemispheres of living mice. To precisely locate the
      implanted capsules, magnetic resonance imaging (MRI) was performed. Fluorescence
      reflectance imaging (FRI) and transillumination fluorescence imaging (TFI) were
      conducted to analyze and compare sensitivity and target-to-background ratios of
      the two methods. The sensitivities of FRI and TFI to background fluorescence from
      circulating dye was tested by imaging fluorescent capsules in mice intravenously
      injected with increasing amounts of long-circulating Cy5.5-dextran. The results
      show that capsules containing dye amounts as low as 10(-12) mol can be detected.
      TFI yielded significantly higher target-to-background ratios than FRI at 10(-11)
      mol (p < .05). Comparatively low amounts of fluorescence in the blood vessels can
      extinguish the signal. We conclude that keeping the signal from circulating NIRF
      dye low, NIRF imaging offers high sensitivity in detecting fluorochromes
      noninvasively within brains of mice, especially by using TFI. This encourages the
      application of NIRF for molecular imaging in the mouse brain using NIRF
      reporters.

PMID- 16954034
TI  - Noninvasive optical imaging of ovarian metastases using Cy5-labeled RAFT-c(-RGDfK
      )4.
AB  - Our group has developed a new molecular tool based on the use of a
      regioselectively addressable, functionalized template (RAFT) scaffold, where four
      cyclic (Arg-Gly-Asp) (cRGD) peptide motifs were grafted. The aim of this study
      was to determine whether RAFT-c(-RGDfK-)4 combined with optical imaging could
      allow noninvasive detection of deep ovarian metastases. Human ovarian
      adenocarcinoma IGROV1 cells expressing low levels of integrin alphaVbeta3 (the
      main receptor for the cRGD peptide) were used for in vitro and in vivo assays in
      combination with Cy5-labeled RAFT-c(-RGDfK-)4, cRGD, or RAFT-c(-RbetaADfK-)4. In
      vivo fluorescence imaging was performed on subcutaneous (SC) tumors and
      intraperitoneal IGROV1 metastases in nude mice. The accumulation of RGD-Cy5
      conjugates in cultured cells or in tumor tissues was examined using confocal
      laser scanning microscopy. RAFT-c(-RGDfK-)4 exhibited stronger staining in vitro,
      enhanced tumor-to-background ratio for sc tumors, and allowed early detection of
      1- to 5-mm large intraabdominal nodules using noninvasive optical imaging.
      Histological study revealed that RAFT-c(-RGDfK-)4 accumulated into tumor
      neovasculature but also into tumor cells. Our data demonstrate that a Cy5-labeled
      RAFT-c(-RGDfK-)4 is an efficient optical probe for early and noninvasive tumor
      detection.

PMID- 16954039
TI  - Genetic parameters for canalisation analysis of litter size and litter weight
      traits at birth in mice.
AB  - The aim of this research was to explore the genetic parameters associated with
      environmental variability for litter size (LS), litter weight (LW) and mean
      individual birth weight (IW) in mice before canalisation. The analyses were
      conducted on an experimental mice population designed to reduce environmental
      variability for LS. The analysed database included 1,976 records for LW and IW
      and 4,129 records for LS. The total number of individuals included in the
      analysed pedigree was 3,997. Heritabilities estimated for the traits under an
      initial exploratory approach varied from 0.099 to 0.101 for LS, from 0.112 to
      0.148 for LW and from 0.028 to 0.033 for IW. The means of the posterior
      distribution of the heritability under a Bayesian approach were the following:
      0.10 (LS), 0.13 (LW) and 0.03 (IW). In general, the heritabilities estimated
      under the initial exploratory approach for the environmental variability of the
      analysed traits were low. Genetic correlations estimated between the trait and
      its variability reached values of -0.929 (LS), -0.815 (LW) and 0.969 (IW). The
      results presented here for the first time in mice may suggest a genetic basis for
      variability of the evaluated traits, thus opening the possibility to be
      implemented in selection schemes.

PMID- 16954040
TI  - Linkage disequilibrium on chromosome 6 in Australian Holstein-Friesian cattle.
AB  - We analysed linkage disequilibrium (LD) in Australian Holstein-Friesian cattle by
      genotyping a sample of 45 bulls for 15 closely-spaced microsatellites on two
      regions of BTA6 reported to carry important QTL for dairy traits. The order and
      distance of markers were based on the USDA-MARC linkage map. Frequencies of
      haplotypes were estimated using the E-M approach and a more computationally
      intensive Bayesian approach as implemented in PHASE. LD was then estimated using
      the Hedrick multiallelic extension of Lewontin normalised coefficient D'.
      Estimates of D' from the two approaches were in close agreement (r = 0.91). The
      mean estimates of D' for marker pairs with an inter-marker distance of less than
      5 cM (n = 13) are 0.57 and 0.51, and for distances more than 20 cM (n = 44) are
      0.29 and 0.17, estimated from the E-M and Bayesian approaches, respectively. The
      Malecot model was fitted for the exponential decline of LD with map distance
      between markers. The swept radii (the distance at which LD has declined to 1/e (
      approximately 37%) of its initial value) are 11.6 and 13.7 cM for the above two
      methods, respectively. The Malecot model was also fitted using map distance in Mb
      from the bovine integrated map (bovine location database, bLDB) in addition to cM
      from the MARC map. Overall, the results indicate a high level of LD on chromosome
      6 in Australian dairy cattle.

PMID- 16954041
TI  - A meta-analytic assessment of a thyroglobulin marker for marbling in beef cattle.
AB  - A meta-analysis was undertaken reporting on the association between a
      polymorphism in the Thyroglobulin gene (TG5) and marbling in beef cattle. A
      Bayesian hierarchical model was adopted, with alternative representations
      assessed through sensitivity analysis. Based on the overall posterior means and
      posterior probabilities, there is substantial support for an additive association
      between the TG5 marker and marbling. The marker effect was also assessed across
      various breed groups, with each group displaying a high probability of positive
      association between the T allele and marbling. The WinBUGS program code used to
      simulate the model is included as an Appendix available online at
      www.edpsciences.org/gse.

PMID- 16954042
TI  - The effects of selective breeding against scrapie susceptibility on the genetic
      variability of the Latxa Black-Faced sheep breed.
AB  - Breeding sheep populations for scrapie resistance could result in a loss of
      genetic variability. In this study, the effect on genetic variability of
      selection for increasing the ARR allele frequency was estimated in the Latxa
      breed. Two sources of information were used, pedigree and genetic polymorphisms
      (fifteen microsatellites). The results based on the genealogical information were
      conditioned by a low pedigree completeness level that revealed the interest of
      also using the information provided by the molecular markers. The overall results
      suggest that no great negative effect on genetic variability can be expected in
      the short time in the population analysed by selection of only ARR/ARR males. The
      estimated average relationship of ARR/ARR males with reproductive females was
      similar to that of all available males whatever its genotype: 0.010 vs. 0.012 for
      a genealogical relationship and 0.257 vs. 0.296 for molecular coancestry,
      respectively. However, selection of only ARR/ARR males implied important losses
      in founder animals (87 percent) and low frequency alleles (30 percent) in the ram
      population. The evaluation of mild selection strategies against scrapie
      susceptibility based on the use of some ARR heterozygous males was difficult
      because the genetic relationships estimated among animals differed when pedigree
      or molecular information was used, and the use of more molecular markers should
      be evaluated.

PMID- 16954043
TI  - Genetic relationships among Turkish sheep.
AB  - Genetic relationships among Turkish sheep breeds were analysed on the basis of 30
      microsatellite markers. Phylogenetic analyses based on the estimation of genetic
      distances revealed the closest relationships for the Akkaraman, Morkaraman and
      Tuj breeds, which were clearly differentiated from the others in the dendrogram.
      Our pattern was completely confirmed by results from the Factorial Correspondence
      Analysis. All the results described analysing either population parameters or
      individuals revealed a clear separation between the fat-tailed group and the
      others. These results, based on nuclear DNA, are discussed along with those
      already reported for these breeds through the investigation of mitochondrial DNA,
      which had revealed the invaluable significance of the genetic background of these
      Turkish sheep.

PMID- 16954045
TI  - Sequence heterogeneity and phylogenetic relationships between the copia
      retrotransposon in Drosophila species of the repleta and melanogaster groups.
AB  - Although the retrotransposon copia has been studied in the melanogaster group of
      Drosophila species, very little is known about copia dynamism and evolution in
      other groups. We analyzed the occurrence and heterogeneity of the copia 5'LTR-ULR
      partial sequence and their phylogenetic relationships in 24 species of the
      repleta group of Drosophila. PCR showed that copia occurs in 18 out of the 24
      species evaluated. Sequencing was possible in only eight species. The sequences
      showed a low nucleotide diversity, which suggests selective constraints
      maintaining this regulatory region over evolutionary time. On the contrary, the
      low nucleotide divergence and the phylogenetic relationships between the D.
      willistoni / Zaprionus tuberculatus / melanogaster species subgroup suggest
      horizontal transfer. Sixteen transcription factor binding sites were identified
      in the LTR-ULR repleta and melanogaster consensus sequences. However, these
      motifs are not homologous, neither according to their position in the LTR-ULR
      sequences, nor according to their sequences. Taken together, the low motif
      homologies, the phylogenetic relationship and the great nucleotide divergence
      between the melanogaster and repleta copia sequences reinforce the hypothesis
      that there are two copia families.

PMID- 16954044
TI  - Polymorphisms of two Y chromosome microsatellites in Chinese cattle.
AB  - Two Y chromosome specific microsatellites UMN2404 and UMN0103 were genotyped and
      assessed for polymorphisms in a total of 423 unrelated males from 25 indigenous
      Chinese cattle breeds. Consistently, both microsatellites displayed specific
      indicine and taurine alleles in each bull examined. The indicine and taurine
      alleles were detected in 248 males (58.6%), and 175 males (41.4%), respectively,
      although these frequencies varied amongst different breeds examined. The indicine
      alleles dominated in the southern group (92.4%), while the taurine alleles
      dominated in the northern group (95.5%). Hainan Island was possibly the site for
      the origin of Chinese zebu, and Tibetan cattle were probably independently
      domesticated from another strain of Bos primigenius. The geographical
      distribution of these frequencies reveals a pattern of male indicine
      introgression and a hybrid zone of indicine and taurine cattle in China. The
      declining south-to-north and east-to-west gradient of male indicine introgression
      in China could be explained by historical data, geographical segregation and
      temperature and weather conditions.

PMID- 16954046
TI  - Comparative analysis of vertebrate EIF2AK2 (PKR) genes and assignment of the
      equine gene to ECA15q24-q25 and the bovine gene to BTA11q12-q15.
AB  - The structures of the canine, rabbit, bovine and equine EIF2AK2 genes were
      determined. Each of these genes has a 5' non-coding exon as well as 15 coding
      exons. All of the canine, bovine and equine EIF2AK2 introns have consensus donor
      and acceptor splice sites. In the equine EIF2AK2 gene, a unique single nucleotide
      polymorphism that encoded a Tyr329Cys substitution was detected. Regulatory
      elements predicted in the promoter region were conserved in ungulates, primates,
      rodents, Afrotheria (elephant) and Insectifora (shrew). Western clawed frog and
      fugu EIF2AK2 gene sequences were detected in the USCS Genome Browser and compared
      to those of other vertebrate EIF2AK2 genes. A comparison of EIF2AK2 protein
      domains in vertebrates indicates that the kinase catalytic domains were
      evolutionarily more conserved than the nucleic acid-binding motifs. Nucleotide
      substitution rates were uniform among the vertebrate sequences with the exception
      of the zebrafish and goldfish EIF2AK2 genes, which showed substitution rates
      about 20% higher than those of other vertebrates. FISH was used to physically
      assign the horse and cattle genes to chromosome locations, ECA15q24-q25 and
      BTA11q12-15, respectively. Comparative mapping data confirmed conservation of
      synteny between ungulates, humans and rodents.

PMID- 16954048
TI  - Genetic characterization of the H9N2 influenza viruses circulated in the poultry
      population in Israel.
AB  - The partial nucleotide sequences of the hemagglutinin (HA) genes of 72 H9N2
      influenza viruses isolated from chickens and turkeys in Israel during the period
      2000-2005 were genetically analyzed. The isolates possessed the three types of
      amino acid motif -R-S-S-R/G-L-, -R-S-N-R/G-L-, and -R-S-K-R/G-L- at the cleavage
      site of HA. Phylogenetic analyses showed that all Israeli isolates belonged to
      the same group which further divided into three closely related sub-groups. The
      HA genes of these isolates were related to the HA gene of
      A/chicken/Germany/R45/98 isolated from chicken in Germany in 1998.

PMID- 16954049
TI  - Targeted intervention for the ultra poor in rural Bangladesh: Does it make any
      difference in their health-seeking behaviour?
AB  - It is now well recognised that regular microcredit intervention is not enough to
      effectively reach the ultra poor in rural Bangladesh, in fact it actively
      excludes them for structural reasons. A grants-based integrated intervention was
      developed (with health inputs to mitigate the income-erosion effect of illness)
      to examine whether such a targeted intervention could change the health-seeking
      behaviour of the ultra-poor towards greater use of health services and "formal
      allopathic" providers during illness, besides improving their poverty status and
      capacity for health expenditure. The study was carried out in three northern
      districts of Bangladesh with high density of ultra poor households, using a pre
      test/post-test control group design. A pre-intervention baseline (2189
      interventions and 2134 controls) survey was undertaken in 2002 followed by an
      intervention (of 18 months duration) and a post-intervention follow-up survey of
      the same households in 2004. Structured interviews were conducted to elicit
      information on health-seeking behaviour of household members. Findings reveal an
      overall change in health-seeking behaviour in the study population, but the
      intervention reduced self-care by 7 percentage units and increased formal
      allopathic care by 9 percentage units. The intervention increased the proportion
      of non-deficit households by 43 percentage units, as well as the capacity to
      spend more than Tk. 25 for treatment of illness during the reference period by 11
      percentage units. Higher health expenditure and time (pre- to -post-intervention
      period) was associated with increased use of health care from formal allopathic
      providers. However, gender differences in health-seeking and health-expenditure
      disfavouring women were also noted. The programmatic implications of these
      findings are discussed in the context of improving the ability of health systems
      to reach the ultra poor.

PMID- 16954051
TI  - Single nucleotide polymorphisms of the ovine calpain 3 (CAPN3) gene.

PMID- 16954050
TI  - Expression of the Escherichia coli IrgA homolog adhesin is regulated by the
      ferric uptake regulation protein.
AB  - The IrgA homolog adhesin (Iha) is an adherence-conferring outer membrane protein
      of Escherichia coli associated with enterohemorrhagic and uropathogenic strains.
      Here, we used primer extension analysis to identify iha promoters in O157:H7 and
      uropathogenic E. coli strains. Transcriptional fusions demonstrated that iha
      transcription is repressed by iron. Gel shifts using purified ferric uptake
      regulator protein (Fur) demonstrated that repression involves a direct
      interaction between Fur and the iha promoter. We identified strain-dependent
      differences in iha expression and determined that single nucleotide polymorphisms
      upstream of the iha promoter, in particular position -85, contribute to
      differences in expression levels.

PMID- 16954052
TI  - Current developments in radiotherapy for paediatric brain tumours.
AB  - This review summarises current developments in radiation oncology and how they
      impact on the management of children with brain tumours. Improved understanding
      of radiobiology has led to attempts to improve the therapeutic ratio with
      hyperfractionated radiotherapy. Recent advances in planning and delivery of
      radiotherapy, including three-dimensional conformal radiotherapy, intensity
      modulated radiotherapy, and proton therapy allow a more precise localisation of
      the maximum dose region with maximum sparing of normal brain. Increasingly
      interactions between drugs and radiotherapy are exploited, but it is important to
      evaluate toxicity of combined modality therapy. The introduction of models to
      predict the impact of radiotherapy dose-volume parameters on long-term
      neuropsychological function will hopefully lead to further benefit with respect
      to sparing of normal tissue morbidity.

PMID- 16954054
TI  - Investigating nurses' knowledge, attitudes, and skills patterns towards clinical
      management system: results of a cluster analysis.
AB  - To determine whether definable subtypes exist within a cohort of Hong Kong nurses
      as related to the clinical management system use in their clinical practices
      based on their knowledge, attitudes, skills, and background factors. Data were
      collected using a structured questionnaire. The sample of 242 registered nurses
      was recruited from three hospitals in Hong Kong. The study employs personal and
      demographic variables, knowledge, attitudes, and skills scale. A cluster analysis
      yielded two clusters. Each cluster represents a different profile of Hong Kong
      nurses on the clinical management system use in their clinical practices. The
      first group (Cluster 1) was labeled 'lower attitudes, less skilful and average
      knowledge' group, and represented 55.4% of the total respondents. The second
      group (Cluster 2) was labeled as 'positive attitudes, good knowledge but less
      skilful'. They comprised almost 44.6% of this nursing sample. Cluster 2 had more
      older nurses, the majority were educated to the baccalaureate or above level,
      with more than 10 years working experience, and they held a more senior ranking
      then Cluster 1. A clear profile of Hong Kong nurses may benefit healthcare
      professionals in making appropriate education or assistance to prompt the use of
      the clinical management system by nurses an officially recognized profession. The
      findings were useful in determining nurse-users' specific needs and their
      preferences for modification of the clinical management system. Such findings
      should be used to formulate strategies to encourage nurses to resolve actual
      problems following computer training and to increase the depth and breadth of
      nurses' knowledge, attitudes, and skills toward such system.

PMID- 16954053
TI  - Information about liver transplantation on the World Wide Web.
AB  - Orthotopic liver transplant (OLTx) has evolved to a successful surgical
      management for end-stage liver diseases. Awareness and information about OLTx is
      an important tool in assisting OLTx recipients and people supporting them,
      including non-transplant clinicians. The study aimed to investigate the nature
      and quality of liver transplant-related patient information on the World Wide
      Web. Four common search engines were used to explore the Internet by using the
      key words 'Liver transplant'. The URL (unique resource locator) of the top 50
      returns was chosen as it was judged unlikely that the average user would search
      beyond the first 50 sites returned by a given search. Each Web site was assessed
      on the following categories: origin, language, accessibility and extent of the
      information. A weighted Information Score (IS) was created to assess the quality
      of clinical and educational value of each Web site and was scored independently
      by three transplant clinicians. The Internet search performed with the aid of the
      four search engines yielded a total of 2,255,244 Web sites. Of the 200 possible
      sites, only 58 Web sites were assessed because of repetition of the same Web
      sites and non-accessible links. The overall median weighted IS was 22 (IQR 1 -
      42). Of the 58 Web sites analysed, 45 (77%) belonged to USA, six (10%) were
      European, and seven (12%) were from the rest of the world. The median weighted IS
      of publications originating from Europe and USA was 40 (IQR = 22 - 60) and 23
      (IQR = 6 - 38), respectively. Although European Web sites produced a higher
      weighted IS [40 (IQR = 22 - 60)] as compared with the USA publications [23 (IQR =
      6 - 38)], this was not statistically significant (p = 0.07). Web sites belonging
      to the academic institutions and the professional organizations scored
      significantly higher with a median weighted IS of 28 (IQR = 16 - 44) and 24(12 -
      35), respectively, as compared with the commercial Web sites (median = 6 with IQR
      of 0 - 14, p = .001). There was an Intraclass Correlation Coefficient (ICC) of
      0.89 and an associated 95% CI (0.83, 0.93) for the three observers on the 58 Web
      sites. The study highlights the need for a significant improvement in the
      information available on the World Wide Web about OLTx. It concludes that the
      educational material currently available on the World Wide Web about liver
      transplant is of poor quality and requires rigorous input from health care
      professionals. The authors suggest that clinicians should pay more attention to
      take the necessary steps to improve the standard of information available on
      their relevant Web sites and must take an active role in helping their patients
      find Web sites that provide the best and accurate information specifically
      applicable to the loco-regional circumstances.

PMID- 16954055
TI  - Customer privacy on UK healthcare websites.
AB  - Privacy has been and continues to be one of the key challenges of an age devoted
      to the accumulation, processing, and mining of electronic information. In
      particular, privacy of healthcare-related information is seen as a key issue as
      health organizations move towards the electronic provision of services. The aim
      of the research detailed in this paper has been to analyse privacy policies on
      popular UK healthcare-related websites to determine the extent to which consumer
      privacy is protected. The author has combined approaches (such as approaches
      focused on usability, policy content, and policy quality) used in studies by
      other researchers on e-commerce and US healthcare websites to provide a
      comprehensive analysis of UK healthcare privacy policies. The author identifies a
      wide range of issues related to the protection of consumer privacy through his
      research analysis using quantitative results. The main outcomes from the author's
      research are that only 61% of healthcare-related websites in their sample group
      posted privacy policies. In addition, most of the posted privacy policies had
      poor readability standards and included a variety of privacy vulnerability
      statements. Overall, the author's findings represent significant current issues
      in relation to healthcare information protection on the Internet. The hope is
      that raising awareness of these results will drive forward changes in the
      industry, similar to those experienced with information quality.

PMID- 16954056
TI  - Treatment of medical databases and their graphical representation on the
      internet.
AB  - The use of new information technologies could facilitate enormously work to
      process and spread knowledge from medical data and, in particular,
      epidemiological data from cancer registries. Cancer registries are official
      institutions that collect information on the occurrence and outcome of cancer in
      defined population groups (city, region, or country). The aim of the present
      project was to design and develop a graphical web system to offer clear
      information about medical information, in this case cancer incidence, using
      Internet technology. A protocol and a system to process, manipulate, and
      represent medical data, epidemiological cancer data, from the Epidemiology Unit
      and Cancer Registry of the Balearic Islands, has been developed. All the steps to
      change the data format to obtain a medical data graphical representation database
      have been described. The result of the project is an application built in
      graphical web format that can be accessed at the following URL: <a
      href="http://gmein.uib.es/registro/resultados/resultados2.htm"
      target="BLANK">http://gmein.uib.es/registro/resultados/resultados2.htm</a>

PMID- 16954057
TI  - Efficacy of stereoscopic visualization and six degrees of freedom interaction in
      preoperative planning of total hip replacement.
AB  - The aim of this study was to assess the accuracy of a six-degrees-of-freedom
      application for pre-operative planning of total hip replacement in a virtual
      reality (VR) environment. A test was performed estimating the system inherent
      accuracy. The users can move objects in the VR environment with an intrinsic
      accuracy almost four orders of magnitude greater than the object dimension. A
      second unambiguous and relevant task was defined to assess the accuracy
      achievable with the interface in a specific planning task. The results were
      compared with those obtained with 2D interfaces for both the stem and the cup
      component. The RMSE was assumed as an indicator of the achievable accuracy. The
      accuracy of the immersive interface was comparable with that achievable with a
      standard mouse - monitor interface. The users were consistent using the VR
      interface, confirming the high usability of the new interface and the steep
      learning curve of users unfamiliar with the new environment. This study has
      demonstrated that the application of VR environment for pre-operative planning of
      total hip replacement may help to shorten the duration of the positioning and to
      yield consistent results even with first-time users.

PMID- 16954058
TI  - Evaluation of internet use in university education by midwifery students.
AB  - The aim of our study was to evaluate the use of the medical Internet by midwifery
      students with analysis of influencing factors and students' preferences. A
      prospective cross-sectional questionnaire study was carried out with 180
      midwifery students. The response rate was 83.8%, 82% use the Internet, and 79.3%
      use the medical resources in their education. The mean accession to the Web is
      5.3 +/- 8.4 times per month. The mean evaluation of information resources for
      books, journals, conferences and university courses was 6.6 +/- 3.2, 4.8 +/- 3.1,
      2.7 +/- 3.0, and 6.8 +/- 3.8, respectively, as measured with the Visual Analogue
      Scale (p < 0.001). Age did not correlate with Internet use and its evaluation but
      correlated with a self-evaluation of Internet skills as a user (Rs = -0.20, p =
      0.016). The evaluation of the Internet as a source of medical knowledge
      correlated with self-evaluation of medical search skills (Rs = 0.66, p < 0.001)
      and user skills (Rs = 0.61, p < 0.001). The medical Internet is used by the
      majority of midwifery students, but it is still a secondary source of
      information, after university training and medical books. The higher evaluation
      of Internet correlated with general computer skills and medical search skills,
      which suggests the need for education on Internet use by students.

PMID- 16954059
TI  - Surfing the net for medical information about psychological trauma: an empirical
      study of the quality and accuracy of trauma-related websites.
AB  - Psychological trauma is a major public-health problem, and trauma victims
      frequently turn to the Internet for medical information related to trauma. The
      Internet has many advantages for trauma victims, including low cost, privacy, use
      of access, and reduced direct social interactions. However, there are no
      regulations on what is posted on the Internet, or by whom, and little is known
      about the quality of information currently available related to the topic of
      psychological trauma. The purpose of this study was to evaluate the quality of
      Internet sites related to the topic of psychological trauma. The top 20 hits for
      searches on Google, AllTheWeb, and Yahoo were tabulated, using search words of
      'psychological trauma', 'stress', 'PTSD', and 'trauma'. From these searches, a
      list of 94 unique unsponsored hits that represented accessible websites was
      generated. Fourteen sites were unrelated or only peripherally related, and eight
      were related but were not comprehensively evaluated because they represented
      brochures, online book sales, etc. Seventy-two websites underwent evaluation of
      the content, design, disclosure, ease of use, and other factors based on
      published guidelines for medical information sites. Forty-two per cent of sites
      had inaccurate information, 82% did not provide a source of their information,
      and 41% did not use a mental-health professional in the development of the
      content. Ratings of content (e.g. accuracy, reliability, etc.) were 4 (2 SD) on a
      scale of 1 - 10, with 10 being the best. There were similar ratings for the other
      variables assessed. These findings suggest that although abundant, websites
      providing information about psychological trauma are often not useful, and can
      sometimes provide inaccurate and potentially harmful information to consumers of
      medical information.

PMID- 16954060
TI  - Effects of gutting and ungutting on microbiological, chemical, and sensory
      properties of aquacultured sea bream (Sparus aurata) and sea bass (Dicentrarchus
      labrax) stored in ice.
AB  - The effect of gutting and ungutting on microbiological, chemical, and sensory
      properties of aqua-cultured sea bream (Sparus aurata) and sea bass (Dicentrarchus
      labrax) stored in ice were studied. The total viable mesophilic and psychrophilic
      bacterial counts increased throughout the storage period of gutted and ungutted
      sea bream and sea bass. The mesophilic counts reached 8.19 log cfu/g for ungutted
      sea bream and 7.93 log cfu/g for ungutted sea bass after 14 days of storage. The
      mesophilic counts reached 8.89 log cfu/g for gutted sea bream and 8.16 log cfu/g
      for gutted sea bass after 14 days of storage. On day 14 of storage the
      psychrophilic counts of ungutted sea bream and sea bass were 8.24 log cfu/g and
      8.03 log cfu/g, respectively, and for gutted sea bream and sea bass were 8.93 and
      8.22, respectively. At the end of the storage period of 14 days, TVB-N, TBA, and
      TMA-N values of ungutted sea bass were determined as 50.13 +/- 0.25 mg/100 g,
      2.66 +/- 0.06 mg malonaldehit/kg, 9.86 +/- 0.01 mg/100 g respectively. TVB-N,
      TBA, and TMA-N values of ungutted sea bream reached 55.90 +/- 0.36 mg/100g, 2.51
      +/- 0.21 mg malonaldehit/kg, 9.79 +/- 0.01 mg/100 g on day 14 respectively. And
      also at the end of the storage period of 14 days, TVB-N, TBA, and TMA-N values of
      gutted sea bass were determined as 48.00 +/- 0.26 mg/100 g, 2.48 +/- 0.03 mg
      malonaldehit/kg, 8.71 +/- 0.06 mg/100 g respectively. TVB-N, TBA, and TMA-N
      values of gutted sea bream reached 49.66 +/- 0.77 mg/100g, 2.64 +/- 0.07 mg
      malonaldehit/kg, 8.97 +/- 0.01 mg/100 g on day 14 respectively. The result of
      this study indicates that the shelf-life of whole ungutted sea bass and sea bream
      stored in ice as determined by the overal acceptibility sensory scores, chemical
      quality, and microbiological results show us that the fish were spoilt on day 14.
      Each chemical, sensory, and microbiological result for sea bream showed us that
      there was a correlation and similarity and on day 14 it was spoilt.

PMID- 16954061
TI  - Food contamination with organic materials in perspective: packaging materials as
      the largest and least controlled source? A view focusing on the European
      situation.
AB  - The comparison of the various sources of food contamination with organic
      chemicals suggests that in the public, but also among experts, the perception of
      risk is often distorted. Firstly, neither pesticides nor environmental pollutants
      contribute the most; the amount of material migrating from food packaging into
      food may well be 100 times higher. Secondly, control of these large migrants is
      often lagging behind the standards set up for other sources, since many of the
      components (particularly those not being "starting materials") have not been
      identified and, thus, not toxicologically evaluated. Finally, attitudes towards
      different types of food contaminants are divergent, also reflected by the legal
      measures: for most sources of food contamination there are strict rules calling
      for minimization, whereas the European packaging industry has even requested a
      further increase in the tolerance to as close as possible to the limit set by the
      toxicologists. This paper calls for a more realistic perception and more coherent
      legal measures-and improvements in the control of migration from packaging
      material.

PMID- 16954062
TI  - Nutritional approach for designing meat-based functional food products with nuts.
AB  - Meat and meat products are essential components of diets in developed countries
      and despite the convincing evidence that relate them to an increased risk for
      CVD, a growing consumption of meat products is foreseen. Epidemiological studies
      show that regular consumption of nuts, in general, and walnuts in particular,
      correlates inversely with myocardial infarction and ischaemic vascular disease.
      We assess the nutritional basis for and technological approach to the development
      of functional meat-based products potentially relevant in cardiovascular disease
      (CVD) risk reduction. Using the available strategies in the meat industry
      (reformulation processes) and a food-based approach, we address the design and
      development of restructured beef steak with added walnuts, potentially functional
      for CVD risk reduction. Its adequacy as a vehicle for active nutrients is
      confirmed by a pharmacokinetic pilot study in humans using gamma-tocopherol as an
      exposure biomarker in chylomicrons during the post-prandial state. Effect and
      potential "functionality" is being assessed by a dietary intervention study in
      subjects at risk and markers and indicators related to CVD are being evaluated.
      Within the conceptual framework of evidence-based medicine, development of meat
      based functional products may become a useful approach for specific applications,
      with a potential market and health benefits of great importance at a population
      level.

PMID- 16954063
TI  - Procyanidin effects on adipocyte-related pathologies.
AB  - Procyanidins, a class of flavonoids, have clear and well-defined beneficial
      effects against several pathologies including cardiovascular heart disease. Now,
      studies in vivo are revealing the effects of procyanidins against obesity, where
      they prevent weight gain and adipose tissue mass increase, and against diabetes
      and insulin resistance, where they act as antihiperglycemic agents. Several
      mechanisms may be responsible for these effects. One of these, due to the key
      role of adipose tissue in the development of obesity and insulin resistance, is
      their effect on adipocytes. In this review we compile the studies that indicate a
      protective role for procyanidins in obesity and insulin resistance, focusing on
      their effects on the adipocyte, where procyanidins modify lipid synthesis, lipid
      degradation, glucose uptake, and adipose differentiation.

PMID- 16954064
TI  - Shigella as a foodborne pathogen and current methods for detection in food.
AB  - Shigella, the causative agent of shigellosis or "bacillary dysentery," has been
      increasingly involved in foodborne outbreaks. According to the Centers for
      Disease Control and Prevention's Emerging Infections Program, Foodborne Diseases
      Active Surveillance Network (FoodNet), Shigella was the third most reported
      foodborne bacterial pathogen in 2002. Foods are most commonly contaminated with
      Shigella by an infected food handler who practices poor personal hygiene.
      Shigella is acid resistant, salt tolerant, and can survive at infective levels in
      many types of foods such as fruits and vegetables, low pH foods, prepared foods,
      and foods held in modified atmosphere or vacuum packaging. Survival is often
      increased when food is held at refrigerated temperatures. Detection methods for
      Shigella include conventional culture methods, immunological methods, and
      molecular microbiological methods. Conventional culture of Shigella in foods is
      often problematic due to the lack of appropriate selective media. Immunological
      methods for Shigella have been researched, yet there is only one commercially
      available test kit. Molecular microbiological methods such as PCR,
      oligonucleotide microarrays, and rep-PCR have also been developed for the
      detection and identification of Shigella. This manuscript reviews the general
      characteristics, prevalence, growth and survival, and methods for detection of
      Shigella in food.

PMID- 16954065
TI  - Membrane technology in degumming, dewaxing, deacidifying, and decolorizing edible
      oils.
AB  - A membrane process offers several advantages over the conventional method of oil
      refining. Conceptually, membranes could be used in almost all stages of
      processing. In the present review, various attempts made by the researchers
      towards degumming, dewaxing, deacidifying, and decolorizing edible oils using
      membrane technology with and without using solvents have been discussed. Attempts
      made with UF and nonporous membranes have demonstrated the ability of these
      membranes to separate phospholipids from undiluted and hexane-diluted oils and a
      high oil flux was obtained with UF membranes in hexane-diluted oils. MF membranes
      were very effective for dewaxing undiluted oils while UF membranes were effective
      in dewaxing hexane-diluted oils without a precooling step. Deacidification was
      successful only with either addition of an alkali followed by membrane filtration
      or by following an indirect route of selective solvent extraction of FFA followed
      by membrane separation. Consistent color reduction in terms of pigments
      (chlorophyll and xanthophylls) and other instrumental measurements (Lovibond and
      visible spectra) could be achieved only with nonporous membranes. Interestingly,
      these membranes did not have selectivity for alpha-and beta-carotenes. UF
      membranes are best suited for degumming and dewaxing applications, while
      nonporous membranes appear to be a better choice for achieving simultaneous
      degumming, dewaxing, and decolorization of oils. Hexane-dilution improved the oil
      flux of nonporous membranes by one order of magnitude, but further improvement is
      desirable for industrial adoption.

PMID- 16954066
TI  - An updated weight of the evidence evaluation of reproductive and developmental
      effects of low doses of bisphenol A.
AB  - There is controversy over whether low doses of bisphenol A (BPA, CAS no. 80-05-7)
      cause reproductive and developmental effects in humans. We update the 2004 weight
      of-evidence assessment of an expert panel convened by Harvard's Center for Risk
      Analysis by critically evaluating over 50 additional studies published between
      April 2002 and February 2006 that examine in vivo reproductive and developmental
      toxicity in mammals at doses <or=5 mg/kg-d. Our findings are consistent with the
      Harvard study: some statistically significant findings in rats and mice exist but
      they are generally countered by more numerous studies showing no effect for
      similar endpoints. No effect is marked or consistent across species, doses, and
      time points. Some mouse studies report morphological changes in testes and sperm
      and some non-oral mouse studies report morphological changes in female
      reproductive organs. Owing to lack of first-pass metabolism, results from non
      oral studies are of limited relevance to oral human exposure. Human biomonitoring
      indicates exposures lower than the "low" doses in the reviewed animal studies.
      Reports of human health impact are very limited and inconsistent. Taken together,
      the weight of evidence does not support the hypothesis that low oral doses of BPA
      adversely affect human reproductive and developmental health.

PMID- 16954068
TI  - Optimal dose of stereotactic radiosurgery for acoustic neuromas: A systematic
      review.
AB  - Radiosurgery is increasingly employed in the treatment of acoustic neuroma, but
      the optimal dose in terms of long-term tumour control and minimal adverse effects
      has not been established. We performed a systematic review of the published
      literature of radiosurgery of acoustic neuroma to assess whether the use of low
      dose radiosurgery is as effective as high dose treatment. Reports of radiosurgery
      for acoustic neuroma were identified through a Medline search. Studies with at
      least 15 patients and a median follow-up longer than 12 months were included. The
      relationship between actuarial 5-year progression-free survival (PFS), and tumour
      and treatment parameters was examined. Forty-two studies were included. Tumour
      control following lower radiosurgery doses was similar to that reported following
      high doses. Only 12 studies reported actuarial outcomes at 5 years. There was no
      relationship between PFS at 5 years and dose to the tumour margin. Radiosurgery
      of larger tumours was associated with lower 5 year PFS (p < 0.05). Although on
      initial inspection radiosurgery of acoustic neuroma with doses of 12 - 13 Gy
      seems to be as effective as higher dose treatment, the available reports are
      subject to a number of confounding factors, are not sufficiently statistically
      powered and there is only limited long-term actuarial outcome data. Currently,
      available studies do not provide sufficient confidence to support the claim that
      low dose radiosurgery is equally effective as higher doses in the long-term
      control of acoustic neuroma.

PMID- 16954069
TI  - Information processing in patients with intracranial tumours: A preliminary
      evaluation of the clinical utility of inspection time.
AB  - Psychomotor slowing is a common feature in many patients with intracranial
      tumours. We therefore performed a preliminary study to determine if inspection
      time, a measure of the efficiency of the brain's information processing, was
      impaired in patients with intracranial tumours. Inspection time, and some other
      neuropsychological and functional tests, were compared in 23 people with
      intracranial tumours and 24 spinal surgery controls prior to surgery. Groups were
      matched for sex, age and education. Inspection time scores were poorer in the
      brain tumour group (p < 0.003) and the effect size was moderate (eta2 = 0.197).
      The brain tumour group also had lower scores on the Boston Aphasia Severity
      Rating Scale, more anxiety on the Hospital Anxiety Depression Scales, but better
      Karnovsky Performance scores. Other cognitive and functional tests showed no
      significant differences between the groups, although group sizes were small.
      There were no significant changes in inspection time after spinal surgery;
      however, after intracranial tumour surgery, approximately 30% of patients showed
      no change, 30% deteriorated and 40% improved. This preliminary study suggests
      that recording inspection time, in a neuro-oncological setting, may prove
      informative and practically useful in assessing non-motor processing speed in
      people with brain tumours.

PMID- 16954070
TI  - One stage reduction and fixation for atlantoaxial spondyloptosis: Report of four
      cases.
AB  - We report four patients having an extremely rare and hitherto unreported clinical
      condition of spondyloptosis of the atlas over axis. Between the year 1999 and
      2004, four patients with spondyloptosis were retrospectively analysed. The age of
      the patients ranged from 12 to 31 years. In three patients, the aetiology of
      spondyloptosis was probably congenital in nature and in one case it was secondary
      to rheumatoid disease. The patients presented with varying degrees of neck pain
      and spastic quadriparesis. All patients were successfully treated by atlantoaxial
      joint distraction, reduction of the dislocation and direct lateral mass plate and
      screw fixation by techniques described earlier by the senior author. Manipulation
      of the atlantoaxial joints and restoring the anatomical craniovertebral
      alignments is possible and probably an ideal treatment of cases with atlantoaxial
      spondyloptosis.

PMID- 16954071
TI  - Long-term outcome in 109 adult patients operated on for hydrocephalus.
AB  - To examine the long-term effects of surgery in adult hydrocephalus we conducted a
      cross-sectional questionnaire study assessing both the patients' sense of well
      being, and changes in gait, living conditions, daily need of sleep and bladder
      function. One-hundred-and-nine consecutive patients operated for non
      communicating hydrocephalus (N-CH) (22) and communicating normal pressure
      hydrocephalus (NPH), both idiopathic (38) and secondary (49) were included. For
      survival analyses, three reference groups were selected from the general
      population and from the Northern Sweden MONICA Project. At long-term follow-up,
      29 (27%) patients had died. Sixty-eight patients (62%) returned the
      questionnaire, while 12 (11%) patients did not reply. The median follow-up time
      was 4.2 years (range 2.3 - 6.2 years). Fifty-four (79%) of these patients
      reported that they still felt improved and 60% had persisting observable
      improvement of gait, living conditions, bladder function and need of sleep.
      Intention-to-treat analyses revealed that 54 (50%) of the patients still felt
      better and 37% remained functionally improved. The standardized mortality ratio
      (observed/expected) was 3.01 (CI: 2.01 - 4.32).

PMID- 16954072
TI  - Stereotactic brain biopsy: An audit of sampling reliability in a clinical case
      series.
AB  - Stereotactic brain biopsy is the current gold standard procedure to obtain a
      neuropathological diagnosis. An audit of 207 stereotactic cases, between January
      1997 and December 2000 was carried out. The aim was to determine the optimum
      number of target sites required to make the final diagnosis and thereby set up
      recommendations for future practice. The overall diagnostic success rate was
      89.3%. A significant positive correlation between the number of targets taken and
      the probability of achieving the final diagnosis was seen. In a subset of
      glioblastoma cases 96.1% of the tumours could have been confidently diagnosed on
      the basis of any two of the targets chosen, although often more targets were
      taken than this. The recommendations made by the audit were: (i) in cases where
      it is suspected the lesion does not require grading, one target site should be
      taken and further sites should only be taken if the first proves to be non
      diagnostic; (ii) in suspected glial series tumours, two targets should be
      routinely taken, with further sites taken only if these prove inconclusive on
      intraoperative smear.

PMID- 16954067
TI  - Modes of action and species-specific effects of di-(2-ethylhexyl)phthalate in the
      liver.
AB  - The industrial plasticizer di-(2-ethylhexyl)phthalate (DEHP) is used in
      manufacturing of a wide variety of polyvinyl chloride (PVC)-containing medical
      and consumer products. DEHP belongs to a class of chemicals known as peroxisome
      proliferators (PPs). PPs are a structurally diverse group of compounds that share
      many (but perhaps not all) biological effects and are characterized as non
      genotoxic rodent carcinogens. This review focuses on the effect of DEHP in liver,
      a primary target organ for the pleiotropic effects of DEHP and other PPs.
      Specifically, liver parenchymal cells, identified herein as hepatocytes, are a
      major cell type that are responsive to exposure to PPs, including DEHP; however,
      other cell types in the liver may also play a role. The PP-induced increase in
      the number and size of peroxisomes in hepatocytes, so called 'peroxisome
      proliferation' that results in elevation of fatty acid metabolism, is a hallmark
      response to these compounds in the liver. A link between peroxisome proliferation
      and tumor formation has been a predominant, albeit questioned, theory to explain
      the cause of a hepatocarcinogenic effect of PPs. Other molecular events, such as
      induction of cell proliferation, decreased apoptosis, oxidative DNA damage, and
      selective clonal expansion of the initiated cells have been also been proposed to
      be critically involved in PP-induced carcinogenesis in liver. Considerable
      differences in the metabolism and molecular changes induced by DEHP in the liver,
      most predominantly the activation of the nuclear receptor peroxisome proliferator
      activated receptor (PPAR)alpha, have been identified between species. Both sexes
      of rats and mice develop adenomas and carcinomas after prolonged feeding with
      DEHP; however, limited DEHP-specific human data are available, even though
      exposure to DEHP and other phthalates is common in the general population. This
      likely constitutes the largest gap in our knowledge on the potential for DEHP to
      cause liver cancer in humans. Overall, it is believed that the sequence of key
      events that are relevant to DEHP-induced liver carcinogenesis in rodents involves
      the following events whereby the combination of the molecular signals and
      multiple pathways, rather than a single hallmark event (such as induction of
      PPARalpha and peroxisomal genes, or cell proliferation) contribute to the
      formation of tumors: (i) rapid metabolism of the parental compound to primary and
      secondary bioactive metabolites that are readily absorbed and distributed
      throughout the body; (ii) receptor-independent activation of hepatic macrophages
      and production of oxidants; (iii) activation of PPARalpha in hepatocytes and
      sustained increase in expression of peroxisomal and non-peroxisomal metabolism
      related genes; (iv) enlargement of many hepatocellular organelles (peroxisomes,
      mitochondria, etc.); (v) rapid but transient increase in cell proliferation, and
      a decrease in apoptosis; (vi) sustained hepatomegaly; (vii) chronic low-level
      oxidative stress and accumulation of DNA damage; (viii) selective clonal
      expansion of the initiated cells; (ix) appearance of the pre-neoplastic nodules;
      (x) development of adenomas and carcinomas.

PMID- 16954073
TI  - Neurosurgical history: Comparing the management of penetrating head injury in
      1969 with 2005.
AB  - Penetrating head trauma may present challenging problems in the acute phase
      (removal of foreign bodies, control of haemorrhage, prevention of infection) and
      in the management of long-term sequelae (neurological deficit, cognitive
      impairment, seizures). Two unusual cases demonstrate the progress made in
      emergency medicine, radiology neurointensive care, and neurosurgical head injury
      management over 36 years.

PMID- 16954074
TI  - De novo meningioma arising at a previous burr hole site.
AB  - A case of meningioma that developed at a site of a previously performed burr hole
      is reported. To the best of our knowledge, this is the first reported case of a
      meningioma arising at a previous burr hole site. The possible reasons for its
      causation are discussed.

PMID- 16954075
TI  - Thoracic intradural extramedullary capillary haemangioma.
AB  - The authors report a rare case of thoracic intradural extramedullary capillary
      haemangioma, the clinical presentation of which was similar to any other
      intraspinal mass. Magnetic resonance imaging does not always distinguish this
      entity from others, but the presence of enlarged vasculature is often a useful
      clue. Complete resection is the treatment of choice of this hamartomatous lesion.

PMID- 16954076
TI  - Disseminated intravascular coagulation complicating resection of a malignant
      meningioma.
AB  - A 70-year-old woman developed disseminated intravascular coagulation (DIC) during
      a craniotomy for a parasagittal anaplastic/malignant meningioma. This was
      successfully treated with rapid resection of the tumour and haematological
      replacement, but a poor neurological outcome resulted. The tumour was
      demonstrated to express tissue factor, an important causative factor in other
      tumour associated DIC and previously shown to be expressed by malignant
      meningiomas. A link between the two is suggested.

PMID- 16954077
TI  - Isolated posterior spinal artery aneurysm.
AB  - Isolated aneurysms of the posterior spinal artery (not associated with
      arteriovenous malformations) are exceptionally rare. Three cases have been
      reported in the literature to date. We report a case of an isolated posterior
      spinal artery aneurysm causing acute subarachnoidal haemorrhage. Spinal artery
      aneurysms are contrasted with the more common intracranial aneurysms in terms of
      presentation and pathogenesis.

PMID- 16954078
TI  - Spontaneous umbilical CSF fistula in an adult as a complication of a
      ventriculoperitoneal shunt.
AB  - Ventriculoperitoneal (VP) shunt is the most commonly used CSF shunt in the modern
      era and widely accepted for the management of hydrocephalus. Numerous abdominal
      complications have been reported in the literature. Spontaneous umbilical fistula
      from VP shunt, although uncommon, has been reported previously in children, but
      never in an adult. This is a case report on an adult who was treated for
      spontaneous umbilical fistula at our unit.

PMID- 16954079
TI  - Aggressive and invasive growth of tectal glioma after surgical intervention and
      chemoradiotherapy.
AB  - A tectal glioma presenting with late-onset aqueduct stenosis and obstructive
      hydrocephalus is usually categorized as a benign glioma. Apparent clinical or
      radiological progression justifies biopsy of the tumour. In this case, an unusual
      tumour shows aggressive and invasive growth after surgical intervention and
      chemoradiotherapy.

PMID- 16954080
TI  - A rare case of recurrent secretory meningioma with malignant transformation.
AB  - A 72-year-old woman previously operated for a sphenoid-ridge meningioma, now
      presented with double vision. Histology showed a secretory meningioma with an
      epithelial-appearing, malignant component. Malignant transformation in a
      secretory meningioma is not known. This is the first report of such an
      occurrence.

PMID- 16954081
TI  - Carotid-cavernous fistula after blunt trauma to the neck.
AB  - Carotid-cavernous fistulas (CCF) are uncommon conditions, but cause significant
      morbidity if untreated. The majority of CCFs in young men are attributed to
      direct skull trauma. We present a case of CCF following a blunt injury to the
      neck.

PMID- 16954082
TI  - Extracranial displacement of a ventricular catheter following trauma.
AB  - We report a case of complete extracranial displacement of the proximal part of a
      ventriculo-peritoneal shunt following trauma. The possible mechanism of the
      delayed displacement of the shunt is discussed. The importance of early
      recognition of this unusual cause of shunt dysfunction is considered.

PMID- 16954083
TI  - Retropharyngeal pseudomeningocele.
AB  - A 38-year-old male was found to have a retropharyngeal pseudomeningocele along
      with C1 - C2 dislocation. Absence of any possible history, misleading
      circumstantial evidence and rarity of the entity made it impossible to diagnose
      the condition preoperatively. Concurrent medical problems dominated and the
      patient died. As a result, outcome of the pseudomeningocele could not be
      evaluated.

PMID- 16954091
TI  - Program development of reminiscence group work for ageing people with
      intellectual disabilities.
AB  - BACKGROUND: The goal of this study was to adapt a narrative reminiscence program
      for the special needs of ageing people with mild/moderate intellectual
      disabilities. Research has shown that stimulating reminiscence in the elderly can
      be a meaningful activity, and holds promise for positive effects on well-being.
      METHOD: In the first stage (10 weeks), the program was developed with 1 group.
      Evaluation and adjustments to the program were made based on video recordings,
      the researcher's log, and feedback from participants and support workers.
      Formative evaluation was performed by means of a within-group analysis. In the
      second stage (3 weeks), the program was introduced to 6 other groups. Interviews
      with professional support workers were subjected to a cross-case analysis.
      RESULTS: The final program consists of 13 sessions covering different
      reminiscence themes. The success of reminiscence group work relies on (a) well
      prepared and structured sessions, (b) adequate use of visual triggers, and (c)
      facilitating, coaching and moderating. CONCLUSION: The program was perceived as a
      valuable and meaningful activity by all participants. Although reminiscence group
      work is not therapeutic in nature, it may have therapeutic use for ageing people
      with intellectual disabilities, and in this sense is worth evaluating.

PMID- 16954090
TI  - Community use of intranasal midazolam for managing prolonged seizures.
AB  - BACKGROUND: Until a few years ago, rectal diazepam (RD) was the only option
      available to parents and carers managing prolonged seizures. However, its use in
      the community was limited due to the requirement for privacy, and because
      education staff in South Australia are not permitted to carry out invasive
      procedures. METHOD: Following a literature review, a seizure management training
      package was developed to enhance the implementation of a trial treatment protocol
      for the administration of intranasal midazolam (INM). Parents, carers and
      education staff were later surveyed about their experiences and perceptions.
      RESULTS: Intranasal midazolam was administered to 131 people (51 children and 80
      adults), with 96.9% control of seizures, and only one minor adverse event.
      Parents expressed a preference for INM over RD because of the shorter time it
      took to take effect and wear off, and the ability to administer it in public if
      necessary. CONCLUSION: Intranasal midazolam is a safe and practical alternative
      to rectal diazepam for managing prolonged seizures in the community.

PMID- 16954092
TI  - Construct and criterion validities of the Service Need Assessment Profile (SNAP):
      a measure of support for people with disabilities.
AB  - BACKGROUND: The Service Need Assessment Profile (SNAP) measures individual
      functional needs in areas of daily living. It produces a support profile,
      detailing the time allocations for staff support to assist in each area of need.
      The Supports Intensity Scale (SIS) is a support needs assessment scale designed
      to provide an objective measure of a person's need for support in medical,
      behavioural, and life activities. SIS can be used for individualised support
      planning, clinical judgements regarding support needs, resource allocation and
      financial planning. The Inventory for Client and Agency Planning (ICAP) assesses
      adaptive and maladaptive behaviours and gathers additional information to
      determine type and amount of special assistance that people with disabilities
      need. METHOD: This study evaluated the construct and criterion validities of SNAP
      in relation to the SIS and ICAP, using assessment data from 114 individuals with
      a range of disabilities and levels of severity. RESULTS: Construct and criterion
      validities were supported for the SNAP by high correlations with SIS, ICAP, and
      staff estimates of support needs and by its capacity to discriminate between sub
      groups in expected ways. CONCLUSIONS: The results provide support for the use of
      SNAP as a support needs instrument.

PMID- 16954094
TI  - The experiences of foster children and youth in special education.
AB  - BACKGROUND: Although a large number of children in foster care in the United
      States are receiving special education services, little is known about their
      educational experiences. METHOD: This exploratory study used focus group research
      to look more closely at the complexity of the problems and needs that this
      population experiences with the special education system. RESULTS: Five major
      procedural issues, relating to identification and placement in special education
      and provision of appropriate services, were identified. CONCLUSION: There is an
      urgent need to address the complex problems that children in foster care
      experience with the special education system. Recommendations are presented for
      closer collaboration between the child welfare and school systems, and for the
      training of educators, social workers, court personnel, and caregivers in special
      education rights and services.

PMID- 16954093
TI  - Rater bias and the measurement of support needs.
AB  - BACKGROUND: The development and use of support need instruments for funding
      disability services is a relatively recent initiative. Although the use of these
      measures appears at face value to provide an objective measure of support needs,
      little is known about their psychometric properties, particularly with respect to
      rater bias and purpose of assessment. A measure of support that has been
      developed in Australia to provide estimates of service needs and associated
      funding is the Service Need Assessment Profile (SNAP). METHOD: This study
      investigated whether SNAP scores obtained for different assessment purposes -
      research and funding - are affected by rater bias, by comparing SNAP to 3 other
      measures of support from 29 people with intellectual disabilities. RESULTS: We
      found that SNAP scores completed for funding purposes showed an individual's
      support needs to be much greater than comparison scores on both SNAP and the 3
      other measures obtained for research purposes. CONCLUSIONS: Our results suggest
      that support measures such as SNAP may significantly overestimate support needs
      when raters know the assessment is being used for funding purposes.

PMID- 16954095
TI  - Menstrual profile and early menopause in women with Down syndrome aged 26-40
      years.
AB  - BACKGROUND: It is known that women with Down syndrome can be fertile, but it is
      not known whether all women with Down syndrome are fertile or sub-fertile. The
      age at menopause for women with Down syndrome is lower compared to women without
      Down syndrome. METHOD: A cross-sectional study of 11 women was undertaken, in
      which the participating women had a blood sample taken and were also examined
      using transabdominal ultrasound scanning (ULS). RESULTS: Definite signs of
      ovulation were evident in 2 women; hormone values in 5 women showed that they
      were in the luteal phase of the menstrual cycle; 1 woman was anovulatory; and in
      1 woman it was not possible to judge the time of the menstrual cycle. Two of the
      women were postmenopausal according to medical information, ultrasound
      examination and hormone values. CONCLUSIONS: Safe contraceptives should be
      considered and offered if women with Down syndrome are engaging in sexual
      relations. Early menopause (before the age of 40 years) and the possibility of
      hormonal replacement therapy should be kept in mind.

PMID- 16954097
TI  - Ethical challenges and complexities of including people with intellectual
      disability as participants in research.

PMID- 16954103
TI  - Formulation and evaluation of Nanostructured Lipid Carrier (NLC)-based gel of
      Valdecoxib.
AB  - Nanostructured Lipid Carrier (NLC)-based topical gel of Valdecoxib was formulated
      with the aim of faster onset yet prolonged action for the treatment of
      inflammation and allied conditions. NLCs prepared by microemulsion template
      technique were characterized by photon correlation spectroscopy for size. Drug
      encapsulation efficiency was determined using Nanosep centrifugal device. The
      nanoparticulate dispersion was suitably gelled and characterized with respect to
      drug content, pH, spreadibility, rheology, and in-vitro release. Safety of the
      NLC-based gel was assessed using primary skin irritation studies, and efficacy
      was confirmed using pharmacodynamic study, namely the Aerosil-induced Rat Paw
      edema model. The developed NLC-based gel showed faster onset and elicited
      prolonged activity up to 24 hours.

PMID- 16954104
TI  - Application of the isolated perfused rat kidney model to assess gender effects on
      drug excretion.
AB  - PURPOSE: To study the effect of gender on the renal disposition of two organic
      anions, p-aminohippuric acid (PAH) and furosemide (FSM) in the isolated perfused
      rat kidney (IPK). METHODS: IPK experiments (3-4 per treatment group) were
      conducted using kidneys from male and female Sprague Dawley rats. PAH was
      administered as a continuous infusion (with loading dose, targeted steady-state
      concentration 10 ug/mL). FSM was added as a bolus dose (2.65 mg, targeted
      concentration 33 ug/mL). Urine was collected in 10-min. intervals and perfusate
      was sampled at the midpoint of each collection period. Control (drug naive)
      perfusions were performed for both genders. PAH and FSM were measured by HPLC.
      Kidney viability (GFR [estimated using inulin clearance], sodium reabsorption,
      glucose reabsorption) was monitored continuously during each perfusion experiment
      (2-h duration). RESULTS: Good kidney function was maintained across all study
      groups, and lower GFR estimates in female kidneys were due to differences in
      kidney weight. For PAH, kidney weight corrected renal clearance (0.88 +/- 0.37
      mL/min/g vs. 0.59 +/- 0.19 mL/min/g) and excretion ratio (3.8 +/- 1.7 vs. 2.2 +/-
      0.72) were significantly higher in male kidneys. For FSM, renal clearance was
      significantly lower in female (0.10 +/- 0.05 mL/min/g) compared to male kidneys
      (0.15 +/- 0.07 mL/min/g). Mass balance analysis showed that FSM cumulative
      urinary excretion was significantly higher and kidney accumulation was
      significantly lower in experiments with male kidneys. CONCLUSIONS: The study
      demonstrates that the IPK is a useful model to assess gender effects on renal
      drug disposition. The renal excretion of organic anions is reduced in female
      rats, possibly due to gender differences in expression and/or activity of
      membrane transporters (both basolateral and luminal) in the kidney.

PMID- 16954105
TI  - Preparation of novel cationic copolymer microspheres and evaluation of their
      function by in vitro and in vivo tests as pH-sensitive drug carrier systems.
AB  - Novel pH-sensitive copolymer microspheres containing methylacrylic acid and
      styrene cross-linking with divinylbenzene were synthesized by free radical
      polymerization. The microspheres that were formed were then characterized by
      Fourier-Transform infrared (FT-IR) spectroscopy, differential scanning
      calorimetry (DSC), size analysis, and X-ray analysis. The copolymer microspheres
      showed pulsatile swelling behavior when the pH of the media changed. The pH
      sensitive microspheres were loaded with diltiazem hydrochloride (DH). The release
      characteristics of the free drug and the drug-loaded microspheres were studied
      under both simulated gastric conditions and intestinal pH conditions. The in vivo
      evaluation of the pulsatile preparation was subsequently carried out using beagle
      dogs as experimental subjects. The results demonstrated that the drug release
      exhibited a pulsatile character both in vitro and in vivo.

PMID- 16954106
TI  - The lyophilization of dispersed systems: influence of freezing process, freezing
      time, freezing temperature and RBCs concentration on RBCs hemolysis.
AB  - In this work, we studied the influence of different parameters controlling
      cooling stage on biological dispersed system injury. The human red blood cell
      (RBCs) was chosen as work model. The study examined the influence of two freezing
      processes on RBCs hemolysis, one process producing big crystals, the other
      producing small crystals. Using both processes, we examined the effect of
      freezing temperature, freezing time, and RBCs concentration on injuries to RBCs.
      Freezing damage was assessed by the hematocrite measure before freezing and after
      thawing. The process producing a small number of big ice crystals (Pa) seems--in
      relation to the one producing a large number of small ice crystals (Pb)--to be
      less traumatic for the RBC, although the two are not statistically different.
      Freezing temperature and freezing time influence the preservation of RBCs. At 0
      and -20 degrees C there were high preservation and total hemolysis, respectively.
      At -5 degrees C and -10 degrees C, the RBC hemolysis depends on freezing
      temperature and freezing time. The RBCs hemolysis rates increases when freezing
      time increases and when freezing temperature decreases. The rates of RBCs
      preserved decreases with RBCs concentration some with either the freezing process
      used (Pa or Pb). More, an accentuation of the difference between the two used
      freezing processes on RBCs hemolysis was retrieved. The analysis of the
      conductivity evolution within the RBCs suspension frozen showed that the
      destruction of the RBCs is had essentially to the solution effects. When the
      crystallization eutectic takes place, the RBCs are already completely destroyed.

PMID- 16954107
TI  - Evaluation of cholecystokinin (CCK-8) peptide thermal stability for use as
      radiopharmaceutical by means isothermal and nonisothermal approaches.
AB  - The purpose of this research was to study the thermal stability of
      cholecystokinin octapeptide (CCK-8) in aqueous solution at pH 12 and ionic
      strength 0.01 M, which were kept as constants, by using isothermal and
      nonisothermal methods. The isothermal decomposition of CCK-8 was investigated as
      a function of temperature (40 degrees C to 70 degrees C). Nonisothermal stability
      studies were performed using a linear increasing temperature program. Two
      different nonisothermal studies were carried out at 0.25 degrees K and 0.5
      degrees K per hour, and the temperature interval varied from 40 degrees C to 82
      degrees C. The degradation of CCK-8 followed first-order kinetics, obeying the
      Arrhenius equation in the experimental temperature range. This indicated that the
      degradation mechanism of CCK-8 could be the equal within the temperature range
      studied. The nonisothermal approach resulted in activation energy (Ea) and shelf
      life (t90%) values that agree well with those obtained by the isothermal method.
      The level of uncertainty in the estimates of t90% and Ea values is determined
      mainly by the extent of drug degradation and temperature change during the
      experiment. Therefore, nonisothermal experiments save time, labor and materials
      (i.e. the amount of drugs necessary to conduct the experiment) compared to the
      classic isothermal experiments, if they are performed using a suitable
      experimental design and a precise analytical method.

PMID- 16954108
TI  - Effect of added Pharmatose DCL11 on the sustained-release of metronidazole from
      Methocel K4M and Carbopol 971P NF floating matrices.
AB  - In vitro dissolution of metronidazole from sustained release floating tablets was
      studied with varied proportions of sodium bicarbonate (SB) and Pharmatose DCL 11.
      Two polymers with different hydration characteristics, Methocel K4M and Carbopol
      971P NF, were used to formulate the matrices. The variables studied include the
      matrices' release profile, hydration volume, and floating behavior. All Methocel
      matrices floated more than 8 h with SB proportions up to 24%, while Carbopol
      matrices floated more than 8 h with SB proportions only up to 12%. Matrices'
      hydration increased with time until reaching a peak and declining thereafter.
      Methocel matrices showed greater hydration volumes and greater drug dissolution
      compared to Carbopol matrices. After adding increasing quantities of Pharmatose
      to matrices containing 12% SB, hydration volume decreased while dissolution
      increased. These results were attributed to water-filled pores that formed
      following the Pharmatose dissolution and to reduced polymer proportions. Carbopol
      matrices showed greater susceptibility to the added Pharmatose, becoming more
      erodible and releasing higher quantities of metronidazole. The greater Carbopol
      susceptibility to added Pharmatose was attributed to its faster hydration.
      Methocel matrices hydrate rapidly only at the surface, delaying hydration and
      Pharmatose dissolution.

PMID- 16954109
TI  - Characteristics of bicalutamide solid dispersions and improvement of the
      dissolution.
AB  - The purpose of our study was to formulate and evaluate bicalutamide (BL) solid
      dispersions (SD). The physicochemical properties were evaluated by differential
      scanning calorimetry (DSC), Fourier-Transform infrared (FT-IR) spectroscopy,
      Powder X-ray diffractometry (PXRD), dissolution studies, and stability studies.
      The dissolution studies demonstrated that the dissolution of BL from BL-SD
      increased with an increase in carrier content (PVP K30). X-ray assays and DSC
      results both confirmed the amorphous state of BL in BL-SD. Stability studies
      conducted after 6 months showed that BL exhibited excellent stability in the
      solid dispersion of PVP K30 (1:5).

PMID- 16954110
TI  - The metabolism of fatty alcohols in lipid nanoparticles by alcohol dehydrogenase.
AB  - Fatty alcohols are commonly used in lipid-based drug delivery systems including
      parenteral emulsions and solid lipid nanoparticles (NPs). The purpose of these
      studies was to determine whether horse liver alcohol dehydrogenase (HLADH), a NAD
      dependent enzyme, could metabolize the fatty alcohols within the NPs and thus
      serve as a mechanism to degrade these NPs in the body. Solid nanoparticles (<100
      nm) were engineered from oil-in-water microemulsion precursors using emulsifying
      wax NF as the oil phase and polyoxyethylene 20-stearyl ether (Brij 78) as the
      surfactant. Emulsifying wax contains both cetyl and stearyl alcohols. NPs were
      incubated with the enzyme and NAD+ at 37 degrees C for up to 48 h, and the
      concentrations of fatty alcohols were quantitatively determined over time by gas
      chromatography (GC). The concentrations of cetyl alcohol and stearyl alcohol
      within the NPs decreased to only 10-20% remaining after 15-24 h of incubation. In
      parallel, NP size, turbidity and the fluorescence intensity of NADH all increased
      over time. It was concluded that horse liver alcohol dehydrogenase/NAD+ was able
      to metabolize the fatty alcohols within the NPs, suggesting that NPs made of
      fatty alcohols may be metabolized in the body via endogenous alcohol
      dehydrogenase enzyme systems.

PMID- 16954111
TI  - The effect of poloxamer viscosity on liquid-filling of solid dispersions in hard
      gelatin capsules.
AB  - Preliminary studies were undertaken on poloxamers to investigate their
      suitability for liquid-fill formulations for hard gelatin capsules. Poloxamers
      with viscosity in the range (0.32-2.8 Pa s) and melting point 48-58 degrees C
      were used as the continuous phase, with alpha-lactose monohydrate of negligible
      solubility in the molten poloxamers, as a model insoluble disperse phase.
      Physicochemical characterization by rheology, melt solidification and moisture
      uptake indicated that poloxamers were suitable excipients for liquid-filling in
      hard gelatin capsules. 10% w/w lactose/poloxamer dispersions were thixotropic and
      shear thinning and exhibited good capsule-filling properties, disperse-phase
      uniformity and satisfactory apparent viscosity at 70 degrees C.

PMID- 16954112
TI  - Characterization of poly(ethylene oxide) as a drug carrier in hot-melt extrusion.
AB  - Poly(ethylene oxide) (PEO) as a drug carrier in hot-melt extrusion was studied by
      using a model drug, nifedipine, in a twin-screw extruder. Binary mixtures of PEO
      and nifedipine have been shown to be amenable to hot-melting at a temperature as
      low as 70 degrees C, well below nifedipine's melting point (172 degrees C). Hot
      stage microscopy provided visual evidence that nifedipine can form a miscible
      dispersion with PEO at 120 degrees C. Complete loss of nifedipine crystallinity
      when extrudated at and above 120 degrees C with a drug loading of 20% (w/w) was
      further confirmed by differential scanning calorimetry (DSC) and X-ray
      diffraction. Cross-sectional imaging of the extrudates using scanning electron
      microscopy indicated homogeneous drug distribution inside PEO when the processing
      temperature was above 120 degrees C. Raman spectroscopy confirmed drug-PEO
      interactions at a molecular level. Cryo-milled extrudates showed significant
      improvement in dissolution rate compared to either pure nifedipine or the
      physical mixture of PEO and nifedipine. A state of supersaturation was achieved
      after 10-minute release in pH 6.8 phosphate buffer. Finally, stability study
      demonstrated that the solid dispersion system is chemically stable for at least 3
      months under the conditions of both 25 degrees C/60% RH and 40 degrees C/75% RH.
      Overall, PEO appears to be a promising aid/carrier to solublize poorly soluble
      drugs through the formation of solid dispersion via hot-melt extrusion, thereby
      improving dissolution and absorption.

PMID- 16954115
TI  - Protocerebral mediodorsal A2' neurosecretory neurons in late pupae of yellow
      mealworm (Tenebrio molitor) after exposure to a static magnetic field.
AB  - The activity of large dorsomedial protocerebral A2' neurosecretory neurons were
      investigated in late pupae of Tenebrio molitor L, which were exposed to a static
      magnetic field of 320 mT. Experimental groups were C: the control group which was
      kept at 5 meters from the magnet; CMF: pupae which were reared in control
      conditions and sacrificed on the eighth day of pupal stage (parents were kept in
      a magnetic field); and MF: pupae kept in a permanent magnetic field for eight
      days. Our results indicate the effects of a static magnetic field on the
      cytological characteristics and activity of large A2' neurosecretory neurons of
      Tenebrio molitor pupae.

PMID- 16954116
TI  - Effects of sub-acute exposure to static magnetic field on hematologic and
      biochemical parameters in pregnant rats.
AB  - This study investigated the effects of a static magnetic field (SMF) on
      hematopoiesis and biochemical parameters in female rats. Pregnant rats were
      exposed to SMF (128 mT-1 hour/day from day 6 to day 19 of pregnancy). At 25
      degrees C, the exposure of rats 1 hour/day for 13 consecutive days to SMF induced
      an increase in hematocrit (Ht) level (+6%, p < 0.05), hemoglobin (Hb)
      concentration (+12%, p < 0.05) and LDH levels (67%, p < 0.05 ), suggesting an
      hypoxia-like state. Moreover, exposure to SMF increased blood glucose and
      decreased insulin release, leading to a diabetic-like state in pregnant rats.

PMID- 16954117
TI  - Sinusoidal magnetic fields and chawki (silkworm) rearing in sericulture.
AB  - Effects of sinusoidal magnetic fields on chawki silkworm rearing have been
      studied. The experiment was conducted using a multi X Bi silkworm hybrid, PM x
      CSR 2. Disease-free layings were reared from hatching to cocooning and by
      subjecting first and second instar to three magnetic field frequencies: 0.1, 1.0,
      and 10 Hz at 1500 nT, pp, for six days at six hours per day. Controls were
      maintained simultaneously. Larval durations for both young-stage chawki (I and
      II) and late stage (III, IV, V) were calculated in days and hours, including the
      feeding and moulting periods for I to IV instars, and the feeding period for V
      instar up to the time of spinning. The study revealed that the magnetic exposures
      reduced both feeding and moulting times with no adverse effects on larval growth.
      The substantial reductions in time, 33 hours in instars I and II, and 64 hours in
      total larval duration, could be commercially important in chawki rearing, saving
      time, leaf consumption, and labor expenses.

PMID- 16954118
TI  - Impedance of goat lens as a function of frequency at DC voltages 0, 50, 100, 200
      mV.
AB  - Impedance characteristics of lens tissue has been studied using the AC impedance
      system (EG&G PARC, model 318) at different low voltage excitations using a Cole
      Cole Plot. The extracellular resistance (Re), intracellular resistance (Ri),
      depressed angle (theta), total impedance (/Z/), and phase angle (phi) of the
      tissue were measured. The impedance locus between the real part (Z') and
      imaginary part (Z'') of the complex impedance of lens was examined at discrete
      frequencies ranging from 10 mHz to 10 Hz. A decrease in extra-cellular resistance
      (Re) and increase in distribution of the factor (alpha) of 56.8 KOmega, 48.1
      KOmega, 32.8 KOmega, 13.4 KOmega, and 0.40, 0.43, 0.46, 0.53 were found at 0 mV,
      50 mV, 100 mV, and 200 mV, respectively. The total impedance (/Z/) and phase
      angle (phi) were also evaluated and the observed frequency dependent for the
      frequency range was tested as a function of excitation voltage. An attempt has
      been made to explain the effect of voltage stress on lens impedance.

PMID- 16954119
TI  - Effect of electric field during incubation of eggs on the immune responses of
      hatched chickens.
AB  - The effects of electric field (EF) during incubation of eggs on the
      immunocompetence of chickens were investigated over a 42-day experimental period.
      Eggs from a meat-type breeder flock were incubated under EF of 30 kV/m, 60 Hz
      during the first 18 days of incubation as compared with the control incubation
      (C). Chickens from the two incubation treatments were fed ad libitum and their
      immune system were monitored. Measurements were made of body weight (BW), and
      lymphoid organs weight (thymus, spleen, and bursa of Fabricius (BOF)) of birds at
      21 and 42 days of age. Immune systems of birds were tested for specific antibody
      responses to sheep red blood cell (SRBC) and Newcastle disease vaccine (NDV), in
      vivo T-lymphocyte proliferation responses to phytohemagglutinin (PHA), and in
      vitro to concanavalin A (Con-A). EF incubation of eggs did not significantly (P >
      0.05) influence BW of bird, absolute weight of lymphoid organs and weight of
      thymus, and BOF as a percentage of BW of bird (% BW) at 21 and 42 days of age,
      humoral immune responses as measured by antibody responses to SRBC and NDV, and
      cell-mediated immune responses as measured by T-lymphocyte proliferation
      responses to PHA, and Con-A of birds when compared with those of the C treatment.
      EF incubation of eggs significantly (P < 0.05) increased spleen weight as a % BW
      at 21 and 42 days of age when compared with those incubated under the C
      treatment. Birds at 42 days of age had significantly (P < 0.01) higher BW,
      lymphoid organ weight, and weight of BOF as a % BW, and lower spleen weight as a
      % BW when compared with those of 21 days of age. It is concluded that the
      incubation of eggs under EF of 30 kV/m, 60 Hz increased spleen weight as a % BW,
      without altering cell-mediated and humoral immune responses and, consequently,
      immunocompetence of meat chickens during the rearing period of 42 days.

PMID- 16954120
TI  - GSM base station electromagnetic radiation and oxidative stress in rats.
AB  - The ever increasing use of cellular phones and the increasing number of
      associated base stations are becoming a widespread source of nonionizing
      electromagnetic radiation. Some biological effects are likely to occur even at
      low-level EM fields. In this study, a gigahertz transverse electromagnetic (GTEM)
      cell was used as an exposure environment for plane wave conditions of far-field
      free space EM field propagation at the GSM base transceiver station (BTS)
      frequency of 945 MHz, and effects on oxidative stress in rats were investigated.
      When EM fields at a power density of 3.67 W/m2 (specific absorption rate = 11.3
      mW/kg), which is well below current exposure limits, were applied, MDA
      (malondialdehyde) level was found to increase and GSH (reduced glutathione)
      concentration was found to decrease significantly (p < 0.0001). Additionally,
      there was a less significant (p = 0.0190) increase in SOD (superoxide dismutase)
      activity under EM exposure.

PMID- 16954121
TI  - Letter to the editor: will we all become electrosensitive?

PMID- 16954123
TI  - Internet interventions for long-term conditions: patient and caregiver quality
      criteria.
AB  - BACKGROUND: Interactive health communication applications (IHCAs) that combine
      high-quality health information with interactive components, such as self
      assessment tools, behavior change support, peer support, or decision support, are
      likely to benefit people with long-term conditions. IHCAs are now largely Web
      based and are becoming known as "Internet interventions." Although there are
      numerous professionally generated criteria to assess health-related websites, to
      date there has been scant exploration of patient-generated assessment criteria
      even though patients and professionals use different criteria for assessing the
      quality of traditional sources of health information. OBJECTIVE: We aimed to
      determine patients' and caregivers' requirements of IHCAs for long-term
      conditions as well as their criteria for assessing the quality of different
      programs. METHODS: This was a qualitative study with focus groups. Patients and
      caregivers managing long-term conditions used three (predominantly Web-based)
      IHCAs relevant to their condition and subsequently discussed the strengths and
      weaknesses of the different IHCAs in focus groups. Participants in any one focus
      group all shared the same long-term condition and viewed the same three IHCAs.
      Patient and caregiver criteria for IHCAs emerged from the data. RESULTS: There
      were 40 patients and caregivers who participated in 10 focus groups. Participants
      welcomed the potential of Internet interventions but felt that many were not
      achieving their full potential. Participants generated detailed and specific
      quality criteria relating to information content, presentation, interactivity,
      and trustworthiness, which can be used by developers and purchasers of Internet
      interventions. CONCLUSIONS: The user-generated quality criteria reported in this
      paper should help developers and purchasers provide Internet interventions that
      better meet user needs.

PMID- 16954124
TI  - Interest in an online smoking cessation program and effective recruitment
      strategies: results from Project Quit.
AB  - BACKGROUND: The Internet is a promising venue for delivering smoking cessation
      treatment, either as a stand-alone program or as an adjunct to pharmacotherapy.
      However, there is little data to indicate what percent of smokers are interested
      in receiving online smoking cessation services or how best to recruit smokers to
      Internet-based programs. OBJECTIVE: Using a defined recruitment sample, this
      study aimed to identify the percentage of smokers who expressed interest in or
      enrolled in Project Quit, a tailored, online, cognitive-behavioral support
      program offered with adjunctive nicotine replacement therapy patches. In
      addition, we examined the effectiveness of several individual-level versus
      population-level recruitment strategies. METHODS: Members from two large health
      care organizations in the United States were invited to participate in Project
      Quit. Recruitment efforts included proactive invitation letters mailed to 34533
      likely smokers and reactive population-level study advertisements targeted to all
      health plan members (> 560000 adults, including an estimated 98000 smokers across
      both health care organizations). RESULTS: An estimated 1.6% and 2.5% of adult
      smokers from each health care organization enrolled in Project Quit. Among likely
      smokers who received proactive study invitations, 7% visited the Project Quit
      website (n = 2260) and 4% (n = 1273) were eligible and enrolled. Response rates
      were similar across sites, despite using different sources to assemble the
      invitation mailing list. Proactive individual-level recruitment was more
      effective than other forms of recruitment, accounting for 69% of website visitors
      and 68% of enrollees. CONCLUSIONS: Smokers were interested in receiving online
      smoking cessation support, even though they had access to other forms of
      treatment through their health insurance. Uptake rates for this program were
      comparable to those seen when smokers are advised to quit and are referred to
      other forms of smoking cessation treatment. In this sample, proactive mailings
      were the best method for recruiting smokers to Project Quit.

PMID- 16954125
TI  - Defining participant exposure measures in Web-based health behavior change
      programs.
AB  - BACKGROUND: Published research on the use of Web-based behavior change programs
      is growing rapidly. One of the observations characterized as problematic in these
      studies is that participants often make relatively few website visits and spend
      only a brief time accessing the program. Properly structured websites permit the
      unobtrusive measurement of the ways in which participants access (are exposed to)
      program content. Research on participant exposure to Web-based programs is not
      merely of interest to technologists, but represents an important opportunity to
      better understand the broader theme of program engagement and to guide the
      development of more effective interventions. OBJECTIVES: The current paper seeks
      to provide working definitions and describe initial patterns of various measures
      of participant exposure to ChewFree.com, a large randomized controlled trial of a
      Web-based program for smokeless tobacco cessation. METHODS: We examined measures
      of participant exposure to either an Enhanced condition Web-based program
      (interactive, tailored, and rich-media program) or a Basic condition control
      website (static, text-based material). Specific measures focused on email
      prompting, participant visits (number, duration, and pattern of use over time),
      and Web page viewing (number of views, types of pages viewed, and Web forum
      postings). RESULTS: Participants in the ChewFree.com Enhanced condition made more
      visits and spent more time accessing their assigned website than did participants
      assigned to the Basic condition website. In addition, exposure data demonstrated
      that Basic condition users thoroughly accessed program content, indicating that
      the condition provided a meaningful, face-valid control to the Enhanced
      condition. CONCLUSIONS: We recommend that researchers conducting evaluations of
      Web-based interventions consider the collection and analysis of exposure measures
      in the broader context of program engagement in order to assess whether
      participants obtain sufficient exposure to relevant program content.

PMID- 16954127
TI  - Pay-for-performance: too much of a good thing? A conversation with Martin Roland.
      Interview by Robert Galvin.
AB  - As the United States moves down the road of pay-for-performance (P4P), concerns
      about unintended consequences are foremost in the minds of policymakers. Initial
      results from the world's most ambitious P4P program, the United Kingdom's Quality
      and Outcomes Framework (QOF), indicate that while quality improvements exceeded
      expectations, so too did the amount of funds paid out, straining the National
      Health Service (NHS) budget. Martin Roland, one of the leading U.K. health
      services researchers and an adviser to the QOF, gives his views on what went
      right and what went wrong, and he offers his advice to the United States about
      using financial incentives to improve quality.

PMID- 16954126
TI  - Mu- and kappa-opioids induce the differentiation of embryonic stem cells to
      neural progenitors.
AB  - Growth factors, hormones, and neurotransmitters have been implicated in the
      regulation of stem cell fate. Since various neural precursors express functional
      neurotransmitter receptors, which include G protein-coupled receptors, it is
      anticipated that they are involved in cell fate decisions. We detected mu-opioid
      receptor (MOR-1) and kappa-opioid receptor (KOR-1) expression and
      immunoreactivity in embryonic stem (ES) cells and in retinoic acid-induced ES
      cell-derived, nestin-positive, neural progenitors. Moreover, these G protein
      coupled receptors are functional, since [D-Ala(2),MePhe(4),Gly-ol(5)]enkephalin,
      a MOR-selective agonist, and U69,593, a KOR-selective agonist, induce a sustained
      activation of extracellular signal-regulated kinase (ERK) signaling throughout a
      24-h treatment period in undifferentiated, self-renewing ES cells. Both opioids
      promote limited proliferation of undifferentiated ES cells via the ERK/MAP kinase
      signaling pathway. Importantly, biochemical and immunofluorescence data suggest
      that [D-Ala(2),MePhe(4),Gly-ol(5)]enkephalin and U69,593 divert ES cells from
      self-renewal and coax the cells to differentiate. In retinoic acid-differentiated
      ES cells, opioid-induced signaling features a biphasic ERK activation profile and
      an opioid-induced, ERK-independent inhibition of proliferation in these neural
      progenitors. Collectively, the data suggest that opioids may have opposite
      effects on ES cell self-renewal and ES cell differentiation and that ERK
      activation is only required by the latter. Finally, opioid modulation of ERK
      activity may play an important role in ES cell fate decisions by directing the
      cells to specific lineages.

PMID- 16954128
TI  - A pilot study on the effects of pre-event manipulation on jump height and running
      velocity.
AB  - PURPOSE: To compare changes in jump height and running velocity with and without
      pre-event high-velocity, low-amplitude manipulation (HVLA). METHODS: A crossover
      study design with elite healthy athletes was used. After a 15 min warm-up, the
      subjects were tested for countermovement jump height (CMJ) and flying 40 m sprint
      time (SPRINT). A sport chiropractor then evaluated each subject. Subjects were
      randomised to either HVLA (applied to joints based on examination) or placebo
      (simulated performance-enhancement stickers). They then rested for 60 min,
      performed another 15 min warm-up, and were retested. The protocol was repeated 48
      h later with the alternative intervention. The mean of two sprints and three
      jumps were analysed, as well as peak performances. The sample size was based on
      prior results from the effects of stretching. RESULTS: 19 subjects involved in
      sprint sports were enrolled; two were too sore to participate on day 2, and one
      could only participate in the jump (all had HVLA on day 1). Of the 17
      participants analysed, seven were female, age range was 19-35, and 17 were
      national or world-class athletes. The ranges for baseline measures were: SPRINT
      4.1-5.5 s; CMJ 47.4-92.7 cm. Overall, the greater than expected variability in
      this pilot study led to the study being underpowered. Subjects tended to perform
      better after HVLA for both CMJ and SPRINT (both mean and peak results), but none
      of the results were statistically significant (p = 0.30-0.61). CONCLUSION:
      Although the larger than expected variability in the pilot study means that the
      observed clinically relevant differences were not statistically significant, the
      direction and magnitude of the changes associated with HVLA suggest that it may
      be beneficial. That said, the increased soreness after HVLA suggests that it may
      be detrimental. HVLA warrants further study.

PMID- 16954129
TI  - Decline in large elastic artery compliance with age: a therapeutic target for
      habitual exercise.

PMID- 16954130
TI  - Transcatheter closure of patent ductus arteriosus with severe pulmonary arterial
      hypertension in adults.
AB  - BACKGROUND: Surgical closure of patent ductus arteriosus (PDA) with severe
      pulmonary arterial hypertension in adults carries higher risk than in children.
      OBJECTIVES: To investigate the application of self-expandable occluders for
      transcatheter closure of PDA associated with severe pulmonary arterial
      hypertension in adults, and the assessment of immediate and short-term results.
      METHODS: 29 adult patients (6 men, 23 women) underwent attempted transcatheter
      closure of PDA at a mean (standard deviation (SD)) age of 31.1 (11.4) years
      (range 18-58 years) and a mean (SD) weight of 54.1 (7.1) kg (range 42-71 kg). On
      the basis of haemodynamic and clinical data obtained before and after trial
      occlusion, the final duct occlusion was determined and carried out. Radiographs
      of the chest, electrocardiograms and echocardiograms were used for follow-up
      evaluation of the treatment within 1 day, 1 month and 3-6 months after successful
      closure. RESULTS: 20 of the 29 patients had successful occlusion (group 1), and 9
      patients failed (named group 2). In group 1, in which occlusion was successful,
      mean (SD) pulmonary arterial pressures decreased markedly after trial occlusion:
      78 (19.3) mm Hg (range 50-125 mm Hg) before occlusion and 41 (13.8) mm Hg (range
      23-77 mm Hg) after occlusion. Systemic arterial oxygen saturation was found to be
      >90% in 19 patients and <90% in the remaining patient before inhalation of
      oxygen, and >95% during inhalation of oxygen or after occlusion in all 20
      patients. In group 2, the occlusion was not successful, because in two patients
      the device was not available; another two patients showed worsening of symptoms.
      The other five patients showed increased pulmonary arterial pressures after trial
      closure; their mean (SD) pulmonary arterial pressures increased by 10.3 (6) mm Hg
      (4-16 mm Hg) after trial occlusion, and systemic arterial oxygen saturation was
      85.5% (2.6%) (range 82.6-88%) before inhalation of oxygen and 94.7% (1.7%) (range
      90.7-99.1%) during inhalation of oxygen. In group 1, the dimensions of the left
      atrium, left ventricle and pulmonary artery increased considerably in 3-6-months
      of follow-up compared with those of preocclusion. CONCLUSIONS: Transcatheter
      closure is an effective treatment for adults with PDA associated with reversible
      severe pulmonary arterial hypertension. Further research is needed for the
      evaluation of long-term results.

PMID- 16954131
TI  - Toll-like receptor 4 gene polymorphisms and myocardial infarction: no association
      in a Caucasian population.
AB  - AIMS: The toll-like receptor 4 (TLR4) is predominantly known for its role as an
      important mediator of immune reactions and has been implicated in the initiation,
      progression, and plaque destabilization stages of atherosclerosis. We
      investigated whether genotypes and haplotypes of the 896A/G (Asp299Gly;
      rs4986790) and 1196C/T (Thr399Ile; rs4986791) single nucleotide polymorphisms of
      the gene encoding the TLR4 were associated with myocardial infarction (MI) in a
      large Caucasian sample. METHODS AND RESULTS: The case group included 3657
      patients with MI and the control group comprised 1211 individuals with
      angiographically normal coronary arteries and without signs or symptoms of MI.
      Genotypes were determined with the use of TaqMan assays. Genotype distributions
      of the 896A/G and 1196C/T polymorphisms were not significantly different between
      the control and patient groups (P> or =0.30). The frequencies of haplotypes
      defined by the 896A/G and 1196C/T polymorphisms were similar between the control
      group and the patient group (P> or =0.16). In addition, the distributions of
      haplotype-defined genotypes (diplotypes) were not significantly different between
      the control group and the patient group (P> or =0.12). Separate analyses in women
      and men did not reveal sex-related associations of specific genotypes or
      haplotypes of the polymorphisms with MI (P> or =0.11). CONCLUSION: The results
      indicate that the 896A/G and 1196C/T polymorphisms of the TLR4 gene or haplotypes
      based on these polymorphisms are not associated with MI.

PMID- 16954132
TI  - Altered status of CD4(+)CD25(+) regulatory T cells in patients with acute
      coronary syndromes.
AB  - AIMS: Considerable evidence supports the role of innate and adaptive immunity in
      the progression and destabilization of the atheromatous plaque. Naturally
      occurring CD4(+)CD25(+) regulatory T cells (Tregs) are a subpopulation of
      lymphocytes that are capable of suppressing the progression of experimental
      autoimmune disorders. We have hypothesized that peripheral numbers and function
      of Tregs would be deranged in patients with acute coronary syndromes (ACS).
      METHODS AND RESULTS: Peripheral numbers of Tregs were evaluated by FACS employing
      labelled antibodies to CD4 and CD25. Functional suppressive properties of Tregs
      were assayed by establishing a triple-cell culture in which purified Tregs were
      incubated with irradiated antigen-presenting cells and anti-CD3-activated
      responder T cells. Proliferation in the presence or absence of oxidized LDL
      (oxLDL) was evaluated by thymidine incorporation. mRNA and protein content of
      foxp3, a master transcriptional regulator of Tregs, were determined for all
      subjects. Patients with ACS exhibited significantly reduced numbers of peripheral
      Tregs as compared with patients with stable angina and normal coronary artery
      subjects. Moreover, oxLDL induced a more profound reduction in Treg numbers in
      patients with ACS. Tregs in ACS patients were significantly compromised as their
      ability to suppress responder CD4(+)CD25(-) T-cell proliferation was attenuated.
      mRNA and protein content of foxp3 were significantly reduced in purified Tregs
      obtained from patients with ACS. CONCLUSION: In patients with ACS, naturally
      occurring CD4(+)CD25(+) Treg numbers are reduced and their functional properties
      compromised. These findings may aid in understanding the mechanisms leading to
      culprit plaque associated T-cell activation in patients with ACS.

PMID- 16954133
TI  - Stroke prophylaxis in atrial fibrillation.

PMID- 16954134
TI  - Acute coronary syndromes and diabetes: Is intensive lipid lowering beneficial?
      Results of the PROVE IT-TIMI 22 trial.
AB  - AIMS: The impact of intensive lipid lowering therapy with statins in acute
      coronary syndrome (ACS) patients with diabetes mellitus (DM) is not well
      characterized. METHODS AND RESULTS: We explored this question in data from the
      Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) TIMI 22
      trial, which tested standard (pravastatin 40 mg) vs. intensive (atorvastatin 80
      mg) statin therapy among patients treated early in the post-ACS period. We
      compared outcomes between patients with DM (identified by history, fasting plasma
      glucose > or =126 mg/dL or haemoglobin A1C > 7%; n = 978) against those without
      DM (n = 3184). The rate of acute cardiac events (death, myocardial infarction,
      and unstable angina requiring rehospitalization) was much higher in patients with
      DM, but was reduced with intensive vs. standard therapy similarly in diabetic
      (21.1 vs. 26.6%, HR = 0.75, P = 0.03) and non-diabetic patients (14.0 vs. 18.0%,
      HR = 0.76, P = 0.002); P-interaction = 0.97. Despite intensive therapy, the
      majority of diabetics (62%) did not reach the dual goal of LDL-C < 70 mg/dL and
      high-sensitivity C-reactive protein <2 mg/L. CONCLUSION: In ACS patients with DM,
      intensive statin therapy reduces acute cardiac events as it does in those without
      DM, with 55 vs. 40 events prevented per 1000 patients treated. However, our data
      highlight the need for additional strategies in this high-risk group.

PMID- 16954135
TI  - Behavioural and psychological symptoms of dementia associated with Parkinson's
      disease.

PMID- 16954136
TI  - Aquaporin NIP2;1 is mainly localized to the ER membrane and shows root-specific
      accumulation in Arabidopsis thaliana.
AB  - We investigated a nodulin 26-like protein NIP2;1, which belongs to the third
      subgroup of Arabidopsis aquaporins. Histochemical analysis of a promoter-beta
      glucuronidase fusion revealed the root-specific expression of NIP2;1. The NIP2;1
      protein was detected in young roots, but not in leaves, stems, flowers or
      siliques. The transient expression of NIP2;1 linked with green fluorescent
      protein in Arabidopsis cultured cells showed its putative endoplasmic reticulum
      (ER) localization. NIP2;1 expressed in yeast cells had low water channel activity
      in the membranes. NIP2;1 may function as a water channel and/or ER channel for
      other small molecules or ions.

PMID- 16954137
TI  - Discovering disease-genes by topological features in human protein-protein
      interaction network.
AB  - MOTIVATION: Mining the hereditary disease-genes from human genome is one of the
      most important tasks in bioinformatics research. A variety of sequence features
      and functional similarities between known human hereditary disease-genes and
      those not known to be involved in disease have been systematically examined and
      efficient classifiers have been constructed based on the identified common
      patterns. The availability of human genome-wide protein-protein interactions
      (PPIs) provides us with new opportunity for discovering hereditary disease-genes
      by topological features in PPIs network. RESULTS: This analysis reveals that the
      hereditary disease-genes ascertained from OMIM in the literature-curated (LC)
      PPIs network are characterized by a larger degree, tendency to interact with
      other disease-genes, more common neighbors and quick communication to each other
      whereas those properties could not be detected from the network identified from
      high-throughput yeast two-hybrid mapping approach (EXP) and predicted
      interactions (PDT) PPIs network. KNN classifier based on those features was
      created and on average gained overall prediction accuracy of 0.76 in cross
      validation test. Then the classifier was applied to 5262 genes on human genome
      and predicted 178 novel disease-genes. Some of the predictions have been
      validated by biological experiments.

PMID- 16954138
TI  - Regression analysis for comparing protein samples with 16O/18O stable-isotope
      labeled mass spectrometry.
AB  - MOTIVATION: Using stable isotopes in global proteome scans, labeled molecules
      from one sample are pooled with unlabeled molecules from another sample and
      subsequently subjected to mass-spectral analysis. Stable-isotope methodologies
      make use of the fact that identical molecules of different stable-isotope
      compositions are differentiated in a mass spectrometer and are represented in a
      mass spectrum as distinct isotopic clusters with a known mass shift. We describe
      two multivariable linear regression models for (16)O/(18)O stable-isotope labeled
      data that jointly model pairs of resolved isotopic clusters from the same peptide
      and quantify the abundance present in each of the two biological samples while
      concurrently accounting for peptide-specific incorporation rates of the heavy
      isotope. The abundance measure for each peptide from the two biological samples
      is then used in down-stream statistical analyses, e.g. differential expression
      analysis. Because the multivariable regression models are able to correct for the
      abundance of the labeled peptide that appear as an unlabeled peptide due to the
      inability to exchange the natural C-terminal oxygen for the heavy isotope, they
      are particularly advantageous for a two-step digestion/labeling procedure. We
      discuss how estimates from the regression model are used to quantify the
      variability of the estimated abundance measures for the paired samples. Although
      discussed in the context of (16)O/(18)O stable-isotope labeled data, the
      multivariable regression models are generalizable to other stable-isotope labeled
      technologies.

PMID- 16954139
TI  - Targeted projection pursuit for visualizing gene expression data classifications.
AB  - We present a novel method for finding low-dimensional views of high-dimensional
      data: Targeted Projection Pursuit. The method proceeds by finding projections of
      the data that best approximate a target view. Two versions of the method are
      introduced; one version based on Procrustes analysis and one based on an
      artificial neural network. These versions are capable of finding orthogonal or
      non-orthogonal projections, respectively. The method is quantitatively and
      qualitatively compared with other dimension reduction techniques. It is shown to
      find 2D views that display the classification of cancers from gene expression
      data with a visual separation equal to, or better than, existing dimension
      reduction techniques. AVAILABILITY: source code, additional diagrams, and
      original data are available from
      http://computing.unn.ac.uk/staff/CGJF1/tpp/bioinf.html

PMID- 16954140
TI  - Synthetic biology--putting engineering into biology.
AB  - Synthetic biology is interpreted as the engineering-driven building of
      increasingly complex biological entities for novel applications. Encouraged by
      progress in the design of artificial gene networks, de novo DNA synthesis and
      protein engineering, we review the case for this emerging discipline. Key aspects
      of an engineering approach are purpose-orientation, deep insight into the
      underlying scientific principles, a hierarchy of abstraction including suitable
      interfaces between and within the levels of the hierarchy, standardization and
      the separation of design and fabrication. Synthetic biology investigates
      possibilities to implement these requirements into the process of engineering
      biological systems. This is illustrated on the DNA level by the implementation of
      engineering-inspired artificial operations such as toggle switching, oscillating
      or production of spatial patterns. On the protein level, the functionally self
      contained domain structure of a number of proteins suggests possibilities for
      essentially Lego-like recombination which can be exploited for reprogramming DNA
      binding domain specificities or signaling pathways. Alternatively, computational
      design emerges to rationally reprogram enzyme function. Finally, the increasing
      facility of de novo DNA synthesis-synthetic biology's system fabrication process
      supplies the possibility to implement novel designs for ever more complex
      systems. Some of these elements have merged to realize the first tangible
      synthetic biology applications in the area of manufacturing of pharmaceutical
      compounds.

PMID- 16954141
TI  - Dynamic partitioning for hybrid simulation of the bistable HIV-1 transactivation
      network.
AB  - MOTIVATION: The stochastic kinetics of a well-mixed chemical system, governed by
      the chemical Master equation, can be simulated using the exact methods of
      Gillespie. However, these methods do not scale well as systems become more
      complex and larger models are built to include reactions with widely varying
      rates, since the computational burden of simulation increases with the number of
      reaction events. Continuous models may provide an approximate solution and are
      computationally less costly, but they fail to capture the stochastic behavior of
      small populations of macromolecules. RESULTS: In this article we present a hybrid
      simulation algorithm that dynamically partitions the system into subsets of
      continuous and discrete reactions, approximates the continuous reactions
      deterministically as a system of ordinary differential equations (ODE) and uses a
      Monte Carlo method for generating discrete reaction events according to a time
      dependent propensity. Our approach to partitioning is improved such that we
      dynamically partition the system of reactions, based on a threshold relative to
      the distribution of propensities in the discrete subset. We have implemented the
      hybrid algorithm in an extensible framework, utilizing two rigorous ODE solvers
      to approximate the continuous reactions, and use an example model to illustrate
      the accuracy and potential speedup of the algorithm when compared with exact
      stochastic simulation. AVAILABILITY: Software and benchmark models used for this
      publication can be made available upon request from the authors.

PMID- 16954142
TI  - Probalign: multiple sequence alignment using partition function posterior
      probabilities.
AB  - MOTIVATION: The maximum expected accuracy optimization criterion for multiple
      sequence alignment uses pairwise posterior probabilities of residues to align
      sequences. The partition function methodology is one way of estimating these
      probabilities. Here, we combine these two ideas for the first time to construct
      maximal expected accuracy sequence alignments. RESULTS: We bridge the two
      techniques within the program Probalign. Our results indicate that Probalign
      alignments are generally more accurate than other leading multiple sequence
      alignment methods (i.e. Probcons, MAFFT and MUSCLE) on the BAliBASE 3.0 protein
      alignment benchmark. Similarly, Probalign also outperforms these methods on the
      HOMSTRAD and OXBENCH benchmarks. Probalign ranks statistically highest (P-value <
      0.005) on all three benchmarks. Deeper scrutiny of the technique indicates that
      the improvements are largest on datasets containing N/C-terminal extensions and
      on datasets containing long and heterogeneous length proteins. These points are
      demonstrated on both real and simulated data. Finally, our method also produces
      accurate alignments on long and heterogeneous length datasets containing protein
      repeats. Here, alignment accuracy scores are at least 10% and 15% higher than the
      other three methods when standard deviation of length is >300 and 400,
      respectively. AVAILABILITY: Open source code implementing Probalign as well as
      for producing the simulated data, and all real and simulated data are freely
      available from http://www.cs.njit.edu/usman/probalign

PMID- 16954143
TI  - DUF283 domain of Dicer proteins has a double-stranded RNA-binding fold.
AB  - Two RNases, Dicer and Argonaute, are at the heart of the RNA interference (RNAi)
      molecular machinery responsible for gene silencing. Both RNases contain multiple
      domains, most of which have been characterized or have functions that can be
      predicted based on sequence comparisons. However, Dicers of higher eukaryotes
      contain the domain known as DUF283 which at present has no assigned role. Using
      sensitive profile-profile comparisons, we detected a divergent double-stranded
      RNA-binding domain coinciding with the DUF283 of Dicer. This finding has
      potential implications regarding the mechanistic role of Dicer in RNAi.

PMID- 16954144
TI  - SEBINI: Software Environment for BIological Network Inference.
AB  - The Software Environment for BIological Network Inference (SEBINI) has been
      created to provide an interactive environment for the deployment and evaluation
      of algorithms used to reconstruct the structure of biological regulatory and
      interaction networks. SEBINI can be used to compare and train network inference
      methods on artificial networks and simulated gene expression perturbation data.
      It also allows the analysis within the same framework of experimental high
      throughput expression data using the suite of (trained) inference methods; hence
      SEBINI should be useful to software developers wishing to evaluate, compare,
      refine or combine inference techniques, and to bioinformaticians analyzing
      experimental data. SEBINI provides a platform that aids in more accurate
      reconstruction of biological networks, with less effort, in less time.
      AVAILABILITY: A demonstration website is located at
      https://www.emsl.pnl.gov/NIT/NIT.html. The Java source code and PostgreSQL
      database schema are available freely for non-commercial use.

PMID- 16954145
TI  - Trypanosome IFT mutants provide insight into the motor location for mobility of
      the flagella connector and flagellar membrane formation.
AB  - The flagella connector (FC) of procyclic trypanosomes is a mobile, transmembrane
      junction important in providing cytotactic morphogenetic information to the
      daughter cell. Quantitative analyses of FC positioning along the old flagellum,
      involving direct observations and use of the MPM2 anti-phosphoprotein monoclonal
      reveals a ;stop point' is reached on the old flagellum which correlates well with
      the initiation of basal body migration and kinetoplast segregation. This
      demonstrates further complexities of the FC and its movement in morphogenetic
      events in trypanosomes than have hitherto been described. We used intraflagellar
      transport RNAi mutants to ablate the formation of a new flagellum. Intriguingly
      the FC could still move, indicating that a motor function beyond the new
      flagellum is sufficient to move it. When such a FC moves, it drags a sleeve of
      new flagellar membrane out of the flagellar pocket. This axoneme-less flagellar
      membrane maintains appropriate developmental relationships to the cell body
      including following the correct helical path and being connected to the internal
      cytoskeleton by macula adherens junctions. Movement of the FC in the apparent
      absence of intraflagellar transport raises the possibility of a new form of
      motility within a eukaryotic flagellum.

PMID- 16954146
TI  - ER stress-induced apoptosis and caspase-12 activation occurs downstream of
      mitochondrial apoptosis involving Apaf-1.
AB  - Accumulation of unfolded proteins induces endoplasmic reticulum (ER) stress.
      Excessive and prolonged stresses lead cells to apoptosis. However, the precise
      molecular mechanisms of ER stress-induced apoptosis have not been fully
      elucidated. We investigated the involvement of the apoptosome in ER stress
      induced cell death pathway using mouse embryonic fibroblasts (MEFs) and mice
      deficient for Apaf-1. Apaf-1-deficient MEFs showed more resistance to ER stress
      inducing reagents as compared with wild type cells. Despite comparable induction
      of ER stress in both wild type and Apaf-1-deficient cells, activation of caspase
      3 was only observed in wild type, but not Apaf-1-deficient, MEFs. Under ER stress
      conditions, BAX translocated to mitochondria and cytochrome c was released from
      mitochondria. We also demonstrated that caspase-12 was processed downstream of
      Apaf-1 and caspase-3, and neither overexpression nor knockdown of caspase-12
      affected susceptibility of the cells to ER stress-induced cell death.
      Furthermore, in the kidneys of Apaf-1-deficient mice, apoptosis induced by in
      vivo administration of tunicamycin was remarkably suppressed as compared with
      wild type mice. These data collectively demonstrated that Apaf-1 and the
      mitochondrial pathway of apoptosis play significant roles in ER stress-induced
      apoptosis.

PMID- 16954147
TI  - Neuronal polarity is regulated by glycogen synthase kinase-3 (GSK-3beta)
      independently of Akt/PKB serine phosphorylation.
AB  - An essential step during the development of hippocampal neurons is the polarised
      outgrowth of a single axon. Recently, it has been suggested that inhibition of
      glycogen synthase kinase-3beta (GSK-3beta) via Akt/PKB-dependent phosphorylation
      of Ser9, specifically at the tip of the presumptive axon, is required for
      selective axonal outgrowth. We now report that, by using neurons from double
      knock-in mice in which Ser9 and Ser21 of the two GSK-3beta isoforms have been
      replaced by Ala, polarity develops independently of phosphorylation at these
      sites. Nevertheless, global inhibition of GSK-3beta disturbs polarity development
      by leading to the formation of multiple axon-like processes in both control and
      knock-in neurons. This unpolarised outgrowth is accompanied by the symmetric
      delivery of membrane components to all neurites. Finally, the adenomatous
      polyposis coli (APC) protein accumulates at the tip of one neurite before and
      during axon elongation, but global inhibition of GSK-3beta leads to APC protein
      accumulation in all neurites. We conclude that GSK-3beta inhibition promotes the
      development of neuronal polarity, but that this is not mediated by Akt/PKB
      dependent phosphorylation.

PMID- 16954148
TI  - The mammalian phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) regulates
      endosome-to-TGN retrograde transport.
AB  - The yeast gene fab1 and its mammalian orthologue Pip5k3 encode the
      phosphatidylinositol 3-phosphate [PtdIns(3)P] 5-kinases Fab1p and PIKfyve,
      respectively, enzymes that generates phosphatidylinositol 3,5-bisphosphate
      [PtdIns(3,5)P(2)]. A shared feature of fab1Delta yeast cells and mammalian cells
      overexpressing a kinase-dead PIKfyve mutant is the formation of a swollen
      vacuolar phenotype: a phenotype that is suggestive of a conserved function for
      these enzymes and their product, PtdIns(3,5)P(2), in the regulation of
      endomembrane homeostasis. In the current study, fixed and live cell imaging has
      established that, when overexpressed at low levels in HeLa cells, PIKfyve is
      predominantly associated with dynamic tubular and vesicular elements of the early
      endosomal compartment. Moreover, through the use of small interfering RNA, it has
      been shown that suppression of PIKfyve induces the formation of swollen endosomal
      structures that maintain their early and late endosomal identity. Although
      internalisation, recycling and degradative sorting of receptors for epidermal
      growth factor and transferrin was unperturbed in PIKfyve suppressed cells, a
      clear defect in endosome to trans-Golgi-network (TGN) retrograde traffic was
      observed. These data argue that PIKfyve is predominantly associated with the
      early endosome, from where it regulates retrograde membrane trafficking to the
      TGN. It follows that the swollen endosomal phenotype observed in PIKfyve
      suppressed cells results primarily from a reduction in retrograde membrane
      fission rather than a defect in multivesicular body biogenesis.

PMID- 16954149
TI  - The contribution of musculoskeletal disorders and physical workload to
      socioeconomic inequalities in health.
AB  - OBJECTIVES: The objective of the study was to examine whether the association of
      physical workload with musculoskeletal disorders might explain occupational
      social class inequalities in self-rated health. METHODS: Participants of the
      study were 40-60 years old employees of the City of Helsinki. The data (n = 3740)
      were derived from several sources, including mail survey designed by the
      researchers and health check-ups carried out by occupational health care.
      Prevalence data and logistic regression were used in the analyses. RESULTS: An
      occupational class gradient was found for musculoskeletal disorders. The gradient
      in musculoskeletal disorders was largely explained by physical demands at work in
      both genders. The contribution of physical demands to occupational class gradient
      in self-rated health was considerable in women, but smaller in men. The
      contribution of musculoskeletal disorder to the occupational class gradient in
      self-rated health was weak for both genders. CONCLUSION: Physical workload is
      likely to considerably contribute to inequalities in health. Mediation of this
      effect through musculoskeletal disorder to generic health, however, could not be
      demonstrated. Different mechanisms are likely to cause inequalities in different
      health outcomes.

PMID- 16954150
TI  - Biodosimetry using chromosome aberrations in human lymphocytes.
AB  - In vitro dose-response calibration curves for (60)Co gamma rays have been
      established for unstable chromosome aberrations in human peripheral blood
      lymphocytes. The observed dose-response data were fitted to a linear quadratic
      model. The calibration curve parameters were used to estimate the equivalent
      whole-body dose and dose to the irradiated region in partial body irradiation of
      cancer patients. The derived partial body doses and fractions of lymphocytes
      irradiated were in agreement with those estimated from the radiotherapy regimes.

PMID- 16954151
TI  - Spontaneous sharp bending of DNA: role of melting bubbles.
AB  - The role of centrally located and distributed base pair mismatches ('melting
      bubbles') on localized bending and stiffness of short dsDNA fragments is
      evaluated using time-dependent fluorescence lifetime measurements. Distributed
      melting bubbles are found to induce larger bending angles and decreased levels of
      stiffness in DNA than centrally located ones of comparable overall size. Our
      results indicate that spontaneous local opening-up of the DNA duplex could
      facilitate sharp bending of short DNA strands even in the absence of DNA binding
      proteins. We also find that the occurrence of two closely spaced melting bubbles
      will generally be favored when a large energetic barrier must be overcome in
      forming the desired bent DNA structure.

PMID- 16954153
TI  - Controversy in clinical endocrinology: problems with reclassification of insulin
      like growth factor I production and action disorders.
AB  - CONTEXT: Recent developments in the IGF field have raised questions on whether
      this is the right time to redefine IGF deficiency. OBJECTIVE: In this
      controversy, arguments are made against the need for redefining IGF deficiency at
      this moment, suggesting instead to wait for further clinical developments. CASE:
      Although a number of rare case reports of IGF deficiency with precise molecular
      etiologies have been described, the vast majority of the cases remain clinically
      defined and without a genetic diagnosis. INTERVENTIONS: Because IGF products are
      now available for clinical use in IGF-deficient patients, we are still using GH
      stimulation and static IGF levels as our only clinical diagnostic and
      classification tools. POSITIONS: We need to develop additional clinical tools,
      side by side with molecular tools, for the diagnosis and subclassification of IGF
      deficiency. Chief among these are the IGF-generation test for identification of
      GH-insensitive patients and genetic panels of polymorphic changes in relevant
      genes. CONCLUSIONS: Until further progress is made in the clinical classification
      of IGF deficiency, we should not change the current classification, and, when we
      do, it should be the responsibility of the relevant societies in the field to
      conduct a consensus statement on the topic first.

PMID- 16954154
TI  - Controversy in clinical endocrinology: reclassification of insulin-like growth
      factor I production and action disorders.
AB  - CONTEXT: The need for the least ambiguous terminology for disorders affecting IGF
      I production and action has become necessary with identification of defects at
      various steps in the GH-IGF-I axis and the promotion of new indications for and
      modalities of growth therapy. No generally agreed-upon or consensus-derived
      classification exists. OBJECTIVE: Our objective was to designate all disorders
      affecting IGF-I production and action by their discrete location, as is already
      done with the defects in pituitary differentiation factors, avoiding imprecise
      and ambiguous terminology. CONCLUSIONS: We propose a pragmatic classification
      that is a precise listing of specific disorders sequentially following the GH-IGF
      I axis, using their accepted designations, and the abolition of nonspecific or
      ambiguous terminology. This concept permits ready insertion of new discoveries.

PMID- 16954155
TI  - Immunolocalization of gonadotropin-releasing hormone (GnRH)-I, GnRH-II, and type
      I GnRH receptor during follicular development in the human ovary.
AB  - CONTEXT: GnRH and its receptor have been detected at the mRNA level in different
      ovarian cell types, implicating an autocrine role of the GnRH system in the human
      ovary. However, the expression at the protein level of GnRH and its receptor in
      specific cell types during follicular development has not been documented in
      humans. OBJECTIVE: We evaluated the immunohistochemical expression of GnRH-I (the
      classical form of mammalian GnRH), GnRH-II (the novel isoform), and the type I
      GnRH receptor (GnRHR) that is known to bind both forms of GnRH, in ovaries of
      premenopausal women. MAIN OUTCOME MEASURES: Immunohistochemistry,
      immunofluorescence, immunoblot assay, and real-time RT-PCR were performed.
      RESULTS: GnRH-I, GnRH-II, and GnRHR were not immunostained in the follicles from
      the primordial to the early antral stage. In preovulatory follicles, both forms
      of GnRH and their common receptor were localized predominantly to the granulosa
      cell layer, whereas the theca interna layer was weakly positive. In the corpus
      luteum, significant levels of GnRH-I, GnRH-II, as well as GnRHR were observed in
      granulosa luteal cells, but not in theca luteal cells. Both GnRH isoforms and the
      type I GnRHR were localized also to the ovarian surface epithelium from which
      over 85% of ovarian cancers are thought to be derived. CONCLUSION: The expression
      of GnRH-I, GnRH-II, and GnRHR protein in the human ovary is temporally and
      spatially specific and further supports the physiological role of an autocrine
      regulatory system involving GnRH-I, GnRH-II, and GnRHR in follicular development
      and corpus luteal function.

PMID- 16954156
TI  - Review: long-term impact of bariatric surgery on body weight, comorbidities, and
      nutritional status.
AB  - CONTEXT: The number of patients who undergo Roux-en-Y gastric bypass (RYGB) and
      gastric banding (GB) surgeries has increased dramatically over the past decade,
      yet the long-term impact of these surgeries on body weight, comorbidities, and
      nutritional status remains unclear, as do the mechanisms of weight regain.
      EVIDENCE ACQUISITION: The articles were found via PubMed searches. To review the
      impact of bariatric surgery on weight maintenance and comorbidities, only
      articles with a postoperative follow-up of 3 yr or longer were included. The
      articles on nutritional status had a follow-up of 12 months or longer.
      CONCLUSIONS: RYGB and GB surgeries lead to substantial weight loss in individuals
      with morbid obesity. However, significant weight regain occurs over the long
      term, and according to the only well-designed prospective controlled study, the
      improvement in comorbidities associated with weight loss mitigates in the long
      term on weight regain. There is some evidence from a retrospective study that
      RYGB surgery is associated with a modest decrease in long-term mortality. These
      results remain to be substantiated by well-designed, long-term, randomized and
      prospective controlled studies. The mechanisms that lead to weight regain need to
      be further examined and may include increase in energy intake due to enlargement
      of stoma and adaptive changes in the levels of gut and adipocyte hormones such as
      ghrelin and leptin, which regulate energy intake; decrease in physical activity;
      changes in energy expenditure; and other factors. In addition to weight regain,
      RYGB surgery is associated with frequent incidence of iron, vitamin B12, folate,
      calcium, and vitamin D deficiency, which requires regular supplementation and
      monitoring.

PMID- 16954157
TI  - Expression of serotonin7 receptor and coupling of ectopic receptors to protein
      kinase A and ionic currents in adrenocorticotropin-independent macronodular
      adrenal hyperplasia causing Cushing's syndrome.
AB  - CONTEXT: In ACTH-independent macronodular adrenal hyperplasia (AIMAH) causing
      Cushing's syndrome, cortisol secretion is controlled by illegitimate membrane
      receptors. OBJECTIVE: The aim of the present study was to characterize the
      pharmacological properties and the transduction mechanisms of illegitimate
      receptors, i.e. receptors for serotonin (5-HT), gastric inhibitory polypeptide
      (GIP), and LH/human chorionic gonadotropin (hCG), expressed by AIMAH tissues to
      evaluate the role of ectopic receptors in the physiopathology of Cushing's
      syndrome. DESIGN: We used in vitro studies on cultured adrenal hyperplasia cells.
      SETTING: The setting was a university research laboratory. PATIENTS: AIMAH
      tissues (H1-H3) were removed from three patients previously screened for
      illegitimate receptors. MAIN OUTCOME MEASURE(S): The main outcome measures were
      steroidogenic and electrical activities of cultured adrenal hyperplasia cells.
      RESULTS: In vitro studies showed that the corticotropic effect of 5-HT was
      mediated by ectopic 5-HT7 receptors in H1 and H2. GIP and hCG stimulated cortisol
      production via activation of cAMP-dependent protein kinase A in H2. On the
      contrary, the protein kinase A inhibitor H-89 did not affect hCG-induced cortisol
      production in H3. Activation of 5-HT7 or GIP receptors enhanced T-type calcium
      current in H1 or H2 and H3, respectively. In addition, GIP reduced the amplitude
      of transient and sustained potassium currents in H2. Conversely, hCG did not
      modify T-type calcium current in H3. CONCLUSIONS: These data show that, besides
      their coupling to the cAMP pathway, illegitimate adrenal receptors can activate
      additional transduction mechanisms, including modulation of membrane channels.

PMID- 16954158
TI  - Hyperinsulinemia, impaired glucose tolerance, and diabetes mellitus in survivors
      of childhood cancer: prevalence and risk factors.
AB  - CONTEXT: Hyperinsulinism and its associated metabolic abnormalities, including
      diabetes mellitus (DM), have been reported in long-term survivors of childhood
      cancer, mainly after bone marrow transplant (BMT); however, the predisposing
      factors are unclear, and early markers have not been identified. METHODS: The
      prevalence of overweight/obesity, abdominal adiposity and hyperinsulinemia (HI),
      impaired glucose tolerance (IGT), or DM was examined prospectively in 248
      survivors of childhood cancer (36 prepubertal, 88 pubertal, and 124 adult
      subjects; 67 BMT) at a median of 12.9 yr (2.3-33.6) after diagnosis and compared
      with healthy controls. Potential risk factors for the development of HI, IGT, or
      DM were sought. RESULTS: Overweight/obesity was not increased when comparing
      subjects with controls; however, the prevalence of abdominal adiposity in
      prepubertal and pubertal subjects was roughly doubled (P < or = 0.04). Fasting
      insulin concentrations were higher in prepubertal and pubertal subjects compared
      with their controls (P < 0.001) and were similar in adult and pubertal subjects.
      HI, IGT, or DM was detected in 39 of 212 (18%) pubertal or adult subjects (23
      BMT). Ten of 88 (11%) pubertal and 14 of 124 (11%) adult subjects had IGT/DM (vs.
      0 and 4.9% controls, respectively; P < 0.001). Total body irradiation, untreated
      hypogonadism, and abdominal adiposity emerged as independent risk factors for the
      development of HI, IGT, or DM in multivariate regression analysis. CONCLUSIONS:
      The risk factors identified suggest the need for reconsideration of BMT protocols
      and regular screening of survivors. The increased prevalence of abdominal
      adiposity among prepubertal subjects, none of whom had developed HI/IGT/DM,
      suggests that a waist to height ratio greater than 0.5 has potential as a
      clinical screening tool.

PMID- 16954159
TI  - Polymorphisms in the ghrelin gene are associated with serum high-density
      lipoprotein cholesterol level and not with type 2 diabetes mellitus in Koreans.
AB  - CONTEXT: Ghrelin is known to play a role in glucose metabolism and in beta-cell
      function. There are controversies regarding the role of ghrelin polymorphisms in
      diabetes and diabetes-related phenotypes. OBJECTIVE: The objective of this study
      was to examine polymorphisms of the ghrelin gene in a Korean cohort and
      investigate associations between them and susceptibility to type 2 diabetes and
      its related phenotypes. DESIGN AND PATIENTS: The ghrelin gene was sequenced to
      identify polymorphisms in 24 DNA samples. Common variants were then genotyped in
      760 type 2 diabetic patients and 641 nondiabetic subjects. Genetic associations
      with diabetes-related phenotypes were also analyzed. RESULTS: Nine polymorphisms
      were identified, and four common polymorphisms [g.-1500C>G, g.-1062G > C, g.-994C
      > T, g.+408C > A (Leu72Met)] were genotyped in a larger study. The genotype
      distributions of these four common polymorphisms in type 2 diabetes patients were
      similar to those of normal nondiabetic controls. However, these four common
      polymorphisms were variably associated with several diabetes-related phenotypes,
      such as high-density lipoprotein (HDL) cholesterol, fasting plasma glucose, and
      homeostasis model assessment of insulin resistance. In particular, subjects
      harboring g.-1062C were associated with a lower serum HDL cholesterol level after
      adjusting for other variables (P = 0.0004 or 0.01 after Bonferroni correction for
      24 tests). CONCLUSION: The aforementioned four common polymorphisms in the
      ghrelin gene were not found to be significantly associated with susceptibility to
      type 2 diabetes mellitus in the Korean population. However, the common
      polymorphism g.-1062G > C in the promoter region of the ghrelin gene was found to
      be significantly associated with serum HDL cholesterol levels.

PMID- 16954160
TI  - Elucidating the underlying molecular pathogenesis of NR3C2 mutants causing
      autosomal dominant pseudohypoaldosteronism type 1.
AB  - CONTEXT: Pseudohypoaldosteronism type 1 (PHA1) is a rare salt-wasting syndrome.
      Mutations in the NR3C2 gene coding for the mineralocorticoid receptor (MR) cause
      autosomal dominant PHA1. OBJECTIVE: Our objective was to reveal the cause of
      renal salt loss in six PHA1 patients and analyze the mutants' functional impact
      on MR function. DESIGN: Our study included the following: clinical and hormonal
      characterization of the patients' phenotype, analysis of the NR3C2 gene,
      determination of receptor affinities to aldosterone and the transcriptional
      activation abilities of the MR mutants, investigation of subcellular
      translocation using fluorescence-labeled MR, and studying changes in mutant
      receptor conformation with proteolysis experiments and three-dimensional
      modeling. RESULTS: Six heterozygous NR3C2 mutations were detected. One frameshift
      mutation (c.1131dupT) has been reported previously. The second frameshift
      mutation (c.2871dupC), which has only recently been reported by our group, showed
      no aldosterone binding and no transactivation because of a major change in
      receptor conformation. Two novel nonsense mutations generate a truncated receptor
      protein. Two missense mutations differently affect MR function. S818L was
      reported recently without complete in vitro data. S818L does not bind aldosterone
      or activate transcription or translocate into the nucleus. A major displacement
      of several residues involved in aldosterone binding was PHA1 causing. The novel
      E972G mutation showed a significantly lower ligand-binding affinity and only 9%
      of wild-type transcriptional activity caused by major changes in receptor
      conformation. CONCLUSIONS: Our data on six mutations extend the spectrum of PHA1
      causing NR3C2 gene mutations. Studying naturally occurring mutants helps to
      clarify their pathogenicity and to identify crucial residues for MR structure and
      function.

PMID- 16954161
TI  - Heat shock treatment of tumor lysate-pulsed dendritic cells enhances their
      capacity to elicit antitumor T cell responses against medullary thyroid
      carcinoma.
AB  - BACKGROUND: In vitro and in vivo studies have shown that dendritic cells (DCs)
      can stimulate antitumor T cell responses against medullary thyroid carcinoma
      (MTC). However, despite promising results in selected cases, the clinical
      efficacy of DC immunotherapy in patients with MTC has been limited. Recently, it
      has been demonstrated in mice that heat shock enhances the capacity of bone
      marrow-derived DCs to stimulate antigen-specific T cells. The aim of our
      investigations was to evaluate whether heat shock also increases the capacity of
      human monocyte-derived DCs to stimulate antitumor T cell responses against MTC
      tumor cells. METHODS: DCs from six patients with metastatic MTC were pulsed with
      tumor lysate derived from allogeneic MTC tumor cells and were heat shocked for 12
      h at 40 C or kept at 37 C. Thereafter, the DCs were matured and cocultured with T
      cells. Finally, the cytotoxic activity of T cells against MTC tumor cells was
      measured in vitro. RESULTS: In all patient samples, cytotoxic T cell responses
      against MTC tumor cells could be induced. Notably, heat-shocked DCs were more
      potent stimulators of cytotoxic T cell responses than control DCs, with T cells
      stimulated with heat-shocked DCs displaying a significantly increased cytotoxic
      activity against MTC tumor cells as compared with T cells stimulated with control
      DCs. In none of the experiments was a cytotoxic T cell response against unrelated
      pancreatic tumor cells (PANC-1) observed, using both control and heat-shocked
      DCs. CONCLUSIONS: Our study shows that heat-shocking DCs may be a valuable
      strategy to increase the immunostimulatory capacity of DCs used for immunotherapy
      of MTC.

PMID- 16954162
TI  - Novel variants in growth differentiation factor 9 in mothers of dizygotic twins.
AB  - CONTEXT: Genes from the ovarian bone morphogenetic signaling pathway (GDF9 and
      BMP15) are critical for normal human fertility. We previously identified a
      deletion mutation in GDF9 in sisters with spontaneous dizygotic (DZ) twins, but
      the prevalence of rare GDF9 variants in twinning families is unknown. OBJECTIVE:
      The objective was to evaluate the frequency of rare variants in GDF9 in families
      with a history of DZ twinning. DESIGN AND SUBJECTS: We recruited 3450 individuals
      from 915 DZ twinning families (1693 mothers of twins) and 1512 controls of
      Caucasian origin. One mother of DZ twins was selected from 279 of the 915
      families, and a DNA sample was screened for rare variants in GDF9 using
      denaturant HPLC. Variants were confirmed by DNA sequencing and genotyped in the
      entire sample by matrix-assisted laser desorption ionization time of flight
      (MALDI-TOF) mass spectrometry. RESULTS: We found two novel insertion/deletions
      (c.392-393insT, c.1268-1269delAA) and four missense alterations in the GDF9
      sequence in mothers of twins. Two of the missense variants (c.307C > T,
      p.Pro103Ser and c.362C > T, p.Thr121Leu) were located in the pro-region of GDF9
      and two (c.1121C > T, p.Pro374Leu and c.1360C > T, p.Arg454Cys) in the mature
      protein region. For each variant, the frequencies were higher in cases compared
      with controls. The proportion of mothers of DZ twins carrying any variant (4.12%)
      was significantly higher (P < 0.0001) than the proportion of carriers in controls
      (2.29%). CONCLUSION: We describe new variants in the GDF9 gene that are
      significantly more common in mothers of DZ twins than controls, suggesting that
      rare GDF9 variants contribute to the likelihood of DZ twinning.

PMID- 16954163
TI  - Expression of HIF-1alpha, HIF-2alpha (EPAS1), and their target genes in
      paraganglioma and pheochromocytoma with VHL and SDH mutations.
AB  - CONTEXT: Activation of the hypoxia-inducible transcription factors HIF-1 and HIF
      2 and a HIF-independent defect in developmental apoptosis have been implicated in
      the pathogenesis of pheochromocytoma (PCC) associated with VHL, SDHB, and SDHD
      mutations. OBJECTIVE: Our objective was to compare protein (HIF-1alpha, EPAS1,
      SDHB, JunB, CCND1, CD34, CLU) and gene (VEGF, BNIP3) expression patterns in VHL
      and SDHB/D associated tumors. RESULTS: Overexpression of HIF-2 was relatively
      more common in VHL than SDHB/D PCC (12 of 13 vs. 14 of 20, P = 0.02), whereas
      nuclear HIF-1 staining was relatively more frequent in SDHB/D PCC (19 of 20 vs.
      13 of 16, P = 0.04). In addition, CCND1 and VEGF expression (HIF-2 target genes)
      was significantly higher in VHL than in SDHB/D PCC. These findings suggest that
      VHL inactivation leads to preferential HIF-2 activation and CCND1 expression as
      described previously in VHL-defective renal cell carcinoma cell lines but not in
      other cell types. These similarities between the downstream consequences of VHL
      inactivation and HIF dysregulation in renal cell carcinoma and PCC may explain
      how inactivation of the ubiquitously expressed VHL protein results in
      susceptibility to specific tumor types. Both VHL and SDHB/D PCC demonstrated
      reduced CLU and SDHB expression. SDHB PCC are associated with a high risk of
      malignancy, and expression of (proapototic) BNIP3 was significantly lower in SDHB
      than VHL PCC. CONCLUSION: Although inactivation of VHL and SDHB/D may disrupt
      similar HIF-dependent and HIF-independent signaling pathways, their effects on
      target gene expression are not identical, and this may explain the observed
      clinical differences in PCC and associated tumors seen with germline VHL and
      SDHB/D mutations.

PMID- 16954164
TI  - Acute in vivo regulation of 11beta-hydroxysteroid dehydrogenase type 1 activity
      by insulin and intralipid infusions in humans.
AB  - CONTEXT: Extraadrenal regeneration of cortisol by 11beta-hydroxysteroid
      dehydrogenase type 1 (11HSD1) is increased after a mixed meal. It is unknown
      which tissue is responsible and whether this reflects the complex transcriptional
      control of 11HSD1 or posttranscriptional control exerted by supply of reduced
      nicotinamide adenine dinucleotide phosphate from hexose-6-phosphate
      dehydrogenase. OBJECTIVE: The objective of this study was to test whether
      hyperinsulinemia and/or increased serum free fatty acids increase whole-body and
      intraadipose 11HSD1, and whether adipose 11HSD1 switches from dehydrogenase to
      reductase activity. METHODS: In nine healthy men, we measured whole-body cortisol
      regeneration (by iv infusion of 9,11,12,12-[2H]4 -cortisol) and intra-adipose
      interconversion of cortisol and cortisone (by sc microdialysis infusion of [3H]4 
      cortisol and [3H]2 -cortisone in separate cannulae) during: 1) a hyperinsulinemic
      euglycemic clamp; 2) iv lipid infusion (Intralipid 20% fat emulsion); and 3)
      saline infusion, each for 3.5 h. RESULTS: Hyperinsulinemia increased rate of
      appearance of 9,12,12-[2H]3 -cortisol (19.3 +/- 0.8 vs. 16.7 +/- 1.1 nmol/min
      with saline, P < 0.001), indicating increased whole-body 11HSD1. Within adipose,
      the predominant reaction was reductase conversion of cortisone to cortisol (after
      3.5 h of saline infusion, reaching 11.0 +/- 2.7% per hour reductase vs. 5.2 +/-
      1.3 dehydrogenase, P < 0.02); insulin increased reductase (reaching 15.8 +/- 3.0,
      P < 0.05) and tended to increase dehydrogenase activity. Intralipid infusion had
      no effects on whole-body deuterated cortisol metabolism, but increased both
      dehydrogenase and reductase (reaching 16.7 +/- 1.8, P < 0.01) activities in
      adipose. CONCLUSIONS: Hyperinsulinemia and increased free fatty acids induce
      acute increases in 11HSD1 activity in adipose tissue that are not attributable to
      a switch from dehydrogenase to reductase. Hyperinsulinemia also increases
      systemic cortisol regeneration. These effects may enhance intracellular cortisol
      concentrations after a meal.

PMID- 16954165
TI  - Genetic variation in the renin-angiotensin system and autonomic nervous system
      function in young healthy Japanese subjects.
AB  - CONTEXT: The renin-angiotensin system (RAS) interacts with the autonomic nervous
      system (ANS) in the regulation of blood pressure and cardiovascular function.
      Several genetic polymorphisms in the RAS have been identified and have been
      implicated as a cause of hypertension and cardiovascular disease. OBJECTIVE: The
      aim of the present study was to evaluate the relation between genetic
      polymorphisms of the RAS (M235T of AGT gene, insertion/deletion of ACE gene,
      A1166C of AT1R gene, and A1675G of AT2R gene) and ANS function. SUBJECTS: One
      hundred forty-nine young healthy Japanese males were genotyped for each RAS
      polymorphism. MAIN OUTCOME MEASURES: ANS function was evaluated by power spectral
      analysis of heart rate variability (HRV) during supine rest and in a standing
      position. RESULTS: In a supine position, subjects homozygous for the AGT 235T
      allele had a higher HRV sympathetic index than 235M allele carriers, whereas the
      orthostatic change in this index was relatively blunted in AGT 235TT carriers. In
      the analysis of gene-gene interaction, these effects of the AGT 235T homozygotes
      on HRV sympathetic index were more apparent in the presence of the ACE D allele.
      Meanwhile, the AT1R 1166C allele was significantly associated with higher HRV low
      frequency power and sympathetic index in a standing position. These data suggest
      that the AGT M235T polymorphism is associated with sympathetic predominance at
      rest, and AT1R 1166C allele carriers have potentially increased sympathetic
      response. CONCLUSIONS: Cardiac autonomic function can be modulated by genetic
      variation in the RAS even in young and healthy states.

PMID- 16954166
TI  - The uremic solute p-cresol decreases leukocyte transendothelial migration in
      vitro.
AB  - Chronic renal failure (CRF) patients display an immunodeficiency state, and
      uremic solutes that accumulate during CRF may be involved in this
      immunodeficiency. In this study, we examined whether the uremic solute para
      cresol (p-cresol), at concentrations similar to those found in patients, alters
      leukocyte transmigration in vitro. We found that p-cresol significantly inhibited
      monocyte THP-1 cell line and PBMCs transmigration across IL-1beta-stimulated
      human umbilical vein endothelial cell (HUVEC) in a static two-compartment model.
      This inhibitory effect of p-cresol persisted in the presence of a physiologic
      concentration of human serum albumin. In order to investigate the mechanism
      involved, expression of endothelial chemokines, fractalkine, monocyte
      chemoattractant protein 1 (MCP-1) and IL-8 and membrane expression of junctional
      adhesion molecule A (JAM-A or JAM-1) were studied. We found that p-cresol
      decreased mRNA expression of the chemokine fractalkine in IL-1beta-stimulated
      HUVEC, without modifying mRNA expression of MCP-1 and IL-8. In addition, p-cresol
      decreased IL-1beta-induced expression of membrane-bound and soluble forms of
      fractalkine and impaired the membrane expression of JAM-A. Taken together, these
      results suggest that p-cresol, by impairing leukocyte transendothelial migration,
      plays a role in the immune dysfunction of uremic patients.

PMID- 16954167
TI  - Novel pan-DR-binding T cell epitopes of adenovirus induce pro-inflammatory
      cytokines and chemokines in healthy donors.
AB  - Adenovirus can cause fatal infections in the immunocompromised host. To date, no
      effective anti-viral therapy is available. Adoptive therapy with adenovirus
      specific T cells could be a promising treatment, but requires the identification
      of such T cells. Aim of this study was to identify conserved adenoviral T cell
      epitopes recognized in a majority of healthy individuals. By using a computer
      algorithm designed to predict pan-HLA-DR-binding T cell epitopes, we selected 19
      peptides of adenovirus serotype 5. PBMCs from 26 healthy subjects were isolated
      and incubated with these peptides to test epitope-specific T cell proliferation.
      Six epitopes derived from E1B protein, hexon protein (two epitopes), DNA
      polymerase, E3A glycoprotein and fiber protein induced a proliferative T cell
      response in the majority of healthy controls. In vitro MHC binding assays
      confirmed the potential capacity of the adenovirus epitopes to bind multiple MHC
      alleles. The cytokine and chemokine profile induced by these epitopes was
      determined with a multiplex immunoassay and revealed a predominant pro
      inflammatory pattern. Based on the broad recognition and the induced cytokine and
      chemokine profile, the detected epitopes can be regarded as potential candidates
      to select adenovirus-specific T cells for immune intervention in the
      immunocompromised host.

PMID- 16954168
TI  - Association of DRESS syndrome with chylous ascites.

PMID- 16954169
TI  - Bioelectrical impedance can be used to predict muscle mass and hence improve
      estimation of glomerular filtration rate in non-diabetic patients with chronic
      kidney disease.
AB  - BACKGROUND: In this article (the second of two companion studies), we report
      whether bioelectrical impedance analysis (BIA) can be used to predict muscle mass
      in patients with chronic kidney disease (CKD), and whether using this predicted
      muscle mass can improve the estimation of glomerular filtration rate (GFR).
      METHODS: Seventy five non-diabetic patients with CKD (mean age +/- SD, 65.1 +/-
      12.0 years; mean GFR 45.9 +/- 28.8 ml/min/1.73 m2) underwent body composition
      analysis by dual energy X-ray absorptiometry to provide a criterion marker of
      skeletal muscle mass (appendicular lean mass, ALM). Validity of a published BIA
      equation to predict ALM was evaluated and a new BIA equation was generated
      (ALM(BIA)) and cross-validated by the leave-one-out procedure. Renal inulin
      clearance provided a criterion measure of GFR (GFR(inu)). The performance of the
      equation including ALM(BIA) to estimate GFR(inu) was compared with demographic
      variables as used in the modification of diet in renal disease (MDRD) equation,
      by determining bias, limits of agreement and accuracy. RESULTS: The previously
      published BIA equation to predict ALM was not valid in these patients with CKD.
      In contrast, our new ALM(BIA) equation cross-validated successfully. Compared
      with the MDRD demographic variables, using ALM(BIA) to predict GFR(inu) improved
      estimation performance, showing reduced bias (4.3 vs 15.6 ml/min) and improved
      limits of agreement (41.1 vs 59.2 ml/min) and accuracy (69.7 vs 39.4% of
      patients' predicted GFR did not deviate by more than 30% of GFR(inu)).
      CONCLUSIONS: ALM(BIA) provides a clinically obtainable and valid method to
      predict muscle mass in patients with CKD, and using ALM(BIA) improves the
      estimation of GFR(inu). Researchers developing future GFR estimation equations
      should consider including ALM(BIA).

PMID- 16954170
TI  - Increase of proteinuria after conversion from calcineurin inhibitor to sirolimus
      based treatment in kidney transplant patients with chronic allograft dysfunction.
AB  - BACKGROUND: Conversion from calcineurin inhibitor to sirolimus, rapamycin has
      become an option in patients with chronic allograft dysfunction (CAD). However,
      in many cases an increase of proteinuria has been observed. The aim was to
      characterize the course of this so far unexplained proteinuria after conversion.
      METHODS: In 149 renal transplant patients from various Spanish centres,
      proteinuria and renal function were analysed 6 months before until 6 months after
      conversion. Patients were divided into three groups according to mean proteinuria
      before conversion (1:<or=300 mg/day; 2:>300-3500 mg/day; 3:>3.5 g/day). RESULTS:
      Generally patients showed an increase of proteinuria from 864+/-1441 (0-12125) to
      1541+/-1878 (0-10976) mg/day after conversion; P<0.001. Group 1: 145+/-92 vs
      669+/-868 mg/day, P<0.001; group 2: 1041+/-799 vs 1995+/-2021 mg/day, P<0.001;
      group 3: 6205+/-3184 vs 4859+/-2122 mg/day, P=NS. Patients with an increase of
      proteinuria of >500 mg/day (n=60; 40%) had a higher serum creatinine before
      conversion compared with patients with no or moderate increase (2.5+/-0.8 vs
      2.15+/-0.72 mg/dl; P=0.002). The group that experienced an increase>500 mg/day
      had a higher serum creatinine after conversion compared with the patients with no
      or moderate increase (2.8+/-1.0 vs 2.1+/-1.2; P<0.001). Of 64 patients, 19 in
      group 1 showed an increase>500 mg/day. CONCLUSION: Conversion for CAD can be
      associated with an increase of proteinuria in patients with pre-existing renal
      damage; however, it preserves renal function in patients with better creatinine
      and proteinuria before conversion, and might not be of benefit if advanced loss
      of renal function and high proteinuria are already present before conversion.

PMID- 16954171
TI  - Recalibration of population-based GFR formulae by pharmacokinetic methods.

PMID- 16954172
TI  - All anti-HBc-positive, HBsAg-negative dialysis patients on the transplant waiting
      list should be regarded as at risk of hepatitis B reactivation post-renal
      transplantation--report of three cases from a single centre.

PMID- 16954173
TI  - Expression and regulation of Toll-like receptors in lupus-like immune complex
      glomerulonephritis of MRL-Fas(lpr) mice.
AB  - BACKGROUND: How microbial infections exacerbate immune complex glomerulonephritis
      remains speculative. Toll-like receptors (TLRs) may be involved in this
      phenomenon, because TLRs have potent immunostimulatory functions when exposed to
      selected pathogen-associated molecules. METHODS: We addressed this issue by
      characterizing the expression of TLR1-9 in MRLlpr/lpr mice that spontaneously
      develop immune complex glomerulonephritis as part of a systemic lupus-like
      autoimmune syndrome. RESULTS: Five-week-old healthy MRLlpr/lpr mice expressed
      TLR3 mRNA in kidneys at comparable levels as in the spleen, while all other TLRs
      were expressed at low levels in the kidney. In 20-week-old nephritic MRLlpr/lpr
      mice, renal mRNA levels had increased for TLR1-9. Renal TLR mRNA originated at
      least in part from glomeruli as evidenced by real-time RT-PCR from laser capture
      microdissected glomeruli. Immunostaining for TLR3, TLR7 and TLR9 revealed their
      expression by F4/80-positive infiltrating macrophages in 20-week-old nephritic
      MRLlpr/lpr mice. In addition, TLR3 localized to glomerular mesangial cells.
      Cultured mesangial cells expressed TLR1-4 and TLR6, while murine macrophages
      expressed TLR1-9. TNF-alpha and IFN-gamma induced TLR2, TLR3 and TLR6 mRNA in
      mesangial cells, while they down-regulated TLR1-9 mRNA in macrophages.
      Stimulation of both cell types with ligands for TLR1-4, TLR5, TLR7 and TLR9
      induced IL-6 production consistent with their respective TLR expression patterns.
      TNF-alpha and IFN-gamma enhanced ligand-induced IL-6 production in both cell
      types irrespective of their modulatory effect on respective TLR mRNA levels.
      CONCLUSION: Thus, cell-type-specific expression and regulation of TLRs may be
      involved in infection-associated exacerbation of immune complex
      glomerulonephritis of MRLlpr/lpr mice.

PMID- 16954174
TI  - Renal allograft failure related to a lower extremity vascular access--a case
      report.

PMID- 16954175
TI  - Ciprofloxacin-induced ANCA-negative cutaneous and renal vasculitis--resolution
      with drug withdrawal.

PMID- 16954176
TI  - Post-transplant lymphoma of the pancreatic allograft in a kidney-pancreas
      transplant recipient: a misleading presentation.

PMID- 16954177
TI  - Idiopathic nodular glomerulosclerosis in a non-diabetic hypertensive smoker--case
      report and review of literature.

PMID- 16954178
TI  - Impact of sodium and ultrafiltration profiling on haemodialysis-related
      hypotension.
AB  - BACKGROUND: Symptomatic hypotension is the most frequent complication in patients
      receiving haemodialysis (HD). Previous studies have reported that the use of
      modulating dialysate sodium concentration or ultrafiltration (UF) rates, or the
      combination use of sodium profile and UF profile may better preserve blood volume
      and reduce the incidence of hypotensive episodes. The aim of this study was to
      evaluate the effects of sodium balance-neutral sodium profile and UF profile and
      their combination on preservation of blood volume, cardiac function and
      occurrence of hypotensive episodes. METHODS: Using Fresenius MC 4008S, eight
      stable HD patients underwent four treatments: (1) control, constant dialysate
      sodium concentration of 138 mmol/l with constant UF; (2) sodium profile, a
      linearly decreasing dialysate sodium concentration (148-131 mmol/l) with constant
      UF; (3) UF profile, a linearly decreasing UF rate with dialysate sodium
      concentration of 138 mmol/l; (4) sodium+UF profile, combination of sodium and UF
      profile. Each treatment was applied in 10 dialysis sessions. Relative blood
      volume (RBV), mean blood pressure (MBP), heart rate (HR), interior vena cava
      diameter (IVCD), stroke volume (SV), cardiac output (CO), plasma sodium
      concentration and the frequency of symptomatic hypotension were monitored.
      RESULTS: There were no significant differences in the IVCD, MBP, SV, CO and body
      weight before dialysis between the three profiles and the control. The total
      plasma protein, haemoglobin, and intradialytic sodium mass removal showed similar
      results. Compared with the control, better preservation of RBV and MBP at 4 and 5
      h and a higher stability in SV variation, but larger UF volume were achieved
      during sodium+UF profile (P<0.05, respectively), the incidence of intradialytic
      hypotension was significantly reduced (P<0.05). CONCLUSIONS: With the similar
      intradialytic sodium removal, during sodium balance-neutral linearly decreasing
      sodium profile combined with linearly decreasing UF profile, greater
      intradialytic stability of the blood volume, blood pressure and cardiac function
      could be obtained, and hypotensive episodes were significantly reduced.

PMID- 16954179
TI  - A sella turcica bridge in subjects with dental anomalies.
AB  - Calcification of the interclinoid ligament (ICL) of the sella turcica, or sella
      turcica bridging, has been associated with severe craniofacial deviations.
      Despite no comprehensive study on the sella turcica bridge, a relationship with
      tooth and eruption disturbances has been reported. In order to investigate
      whether congenital absence of the second mandibular premolar, or the presence of
      a palatally displaced canine (PDC), is associated with sella bridging, a
      retrospective study was performed. Lateral cephalometric radiographs from 20
      males and 14 females, aged between 8 and 16 years, with a PDC and second
      mandibular premolar aplasia were reviewed and compared with a control group. A
      standardized scoring scale was established to quantify the extent of a sella
      turcica bridge from each radiograph (no calcification, partially calcified, and
      completely calcified). The prevalence of complete calcification of the ICL in
      adolescents with dental anomalies was equal to 17.6 per cent, while an incidence
      9.9 per cent was found in the control group. A partially calcified sella turcica
      was observed in 58.8 per cent of adolescents with dental anomalies compared with
      33.7 per cent in the control group. The association between the degree of
      calcification of the ICL and the presence of dental anomalies in the studied
      adolescents was statistically significant according to chi-square statistics (P =
      0.004). This was confirmed by Fisher's exact test (P = 0.003). According to these
      findings, the prevalence of a sella turcica bridge in adolescents with dental
      anomalies is increased, while age and gender do not greatly influence
      ossification of the ICL. The very early appearance during development of a sella
      turcica bridge should alert clinicians to possible tooth anomalies in life later.

PMID- 16954180
TI  - Inclination of the occlusal plane is associated with the direction of the
      masticatory movement path.
AB  - Using lateral cephalograms and a jaw movement-recording system, the relationship
      between the masticatory movement path and dentofacial morphology was investigated
      in 17 subjects (9 males and 8 females, mean age 23.5 years) without a history of
      orthodontic treatment. The masticatory movement path was measured at the right
      and left lower first molar while the subjects chewed gum. The angle between the
      Frankfort horizontal plane and the masticatory axis (FH-masticatory angle),
      defined as the axis passing the opening and closing turning point on the sagittal
      masticatory path, was also measured. The correlation between the angular
      measurements derived from the lateral cephalogram and the FH-masticatory angle
      was then investigated. A positive correlation was observed in the FH-masticatory,
      occlusal plane (P < 0.05), and mandibular plane (P < 0.01) angles. Furthermore,
      it was found that the angle between the masticatory axis and the occlusal plane
      (69.1 +/- 4.2 degrees) remained constant even as the masticatory axis showed a
      tendency to incline forward as the mandibular plane angle became steeper; the
      rates of change of the FH-masticatory and the occlusal plane angles were
      approximately 1:1. This finding suggests that the masticatory movement path is
      closely associated with the occlusal plane.

PMID- 16954181
TI  - Improvement of pseudoelasticity and ductility of Beta III titanium alloy-
      application to orthodontic wires.
AB  - The pseudoelasticity of metastable Beta III titanium alloy (TMAtrade mark) used
      for orthodontic applications is obtained by cold wiredrawing. This wire has
      higher rigidity than cold-drawn NiTi (Nitinoltrade mark, superelastic NiTi SE)
      and lower recoverable deformation. The low ductility value of Beta III is due to
      the deformation imposed by wiredrawing. The aim of this research was to improve
      the behaviour of this alloy by modifying the microstructural parameters to
      decrease the rigidity and increase the recoverable deformation and ductility of
      the alloy. The effects of second phase precipitate, grain size, and deformation
      on the wire mechanical properties were also examined. The isothermal
      precipitation of alpha (alpha) or omega (omega(isoth)) phases precludes the
      expression of the pseudoelastic effect. The presence of an omega(isoth) phase
      considerably increases fracture strength, whereas the alpha phase strongly
      decreases the ductility and adversely affects the strain recovery (epsilon(r)).
      To control the grain size, the growth of the recrystallized grains was studied by
      considering several parameters, which are known to have an influence on grain
      size, including the cold rolled strain, the temperature, the time of annealing,
      and the initial grain size. A structure with coarse grains, quenched from a
      temperature higher than the beta transus (T(beta)), associated with a plastic pre
      deformation, contributed to an improved pseudoelastic behaviour, due to the
      presence of a reversible martensite phase (alpha'') induced by the pre
      deformation.

PMID- 16954182
TI  - Profile of Svante Paabo.

PMID- 16954183
TI  - Absolute brain size: did we throw the baby out with the bathwater?

PMID- 16954184
TI  - Host defenses against Staphylococcus aureus infection require recognition of
      bacterial lipoproteins.
AB  - Toll-like receptors and other immune-signaling pathways play important roles as
      sensors of bacterial pattern molecules, such as peptidoglycan, lipoprotein, or
      teichoic acid, triggering innate host immune responses that prevent infection.
      Immune recognition of multiple bacterial products has been viewed as a safeguard
      against stealth infections; however, this hypothesis has never been tested for
      Staphylococcus aureus, a frequent human pathogen. By generating mutations that
      block the diacylglycerol modification of lipoprotein precursors, we show here
      that S. aureus variants lacking lipoproteins escape immune recognition and cause
      lethal infections with disseminated abscess formation, failing to elicit an
      adequate host response. Thus, lipoproteins appear to play distinct, nonredundant
      roles in pathogen recognition and host innate defense mechanisms against S.
      aureus infections.

PMID- 16954185
TI  - Advanced glycation end product (AGE) receptor 1 suppresses cell oxidant stress
      and activation signaling via EGF receptor.
AB  - Advanced glycation end product receptors (AGERs) play distinct functional roles
      in both the toxicity and disposal of advanced glycation end products (AGEs),
      substances that are linked to diabetes and aging. Overexpression of AGER1 in
      murine mesangial cells (MCs) (MC-R1) inhibited AGE-induced MAPK1,2
      phosphorylation and NF-kappaB activity and also increased AGE degradation. The
      mechanism of the inhibitory effects of AGER1, upstream of MAPK, was explored in
      MCs and HEK293 AGER1-expressing cells. AGE-induced Ras activation was found to be
      linked to Shc/Grb2 complex formation and Shc phosphorylation in MCs, responses
      that were markedly reduced in MC-R1 cells. AGE responses also included EGF
      receptor (EGFR) phosphorylation in MCs or HEK293 cells, but this link was blocked
      in both MC-R1 and HEK293-R1 cells. Coexpression of AGER1 and EGFR in HEK293 cells
      decreased AGE-mediated EGFR and p44/p42 phosphorylation but not EGF-induced
      p44/p42 activation. AGE, S100/calgranulin, or H(2)O(2) promoted MAPK
      phosphorylation in EGFR(+) cells in a manner that was inhibitable by an EGFR
      inhibitor, AG1478. Also, in AGER1 cells, AGE-induced H(2)O(2) formation and AGE-
      or S100-induced p44/p42 phosphorylation were suppressed, and these effects were
      restored by R1 siRNA. These data confirm that R1 negatively regulates AGE
      mediated oxidant stress-dependent signaling via the EGFR and Shc/Grb2/Ras
      pathway. AGER1 could serve as a model for developing therapeutic targets against
      vascular and kidney disorders related to diabetes and aging.

PMID- 16954186
TI  - Intersubunit signaling in glutamate-1-semialdehyde-aminomutase.
AB  - Enzymes are highly dynamic and tightly controlled systems. However, allosteric
      communication linked to catalytic turnover is poorly understood. We have
      performed an integrated approach to trap several catalytic intermediates in the
      alpha2-dimeric key enzyme of chlorophyll biosynthesis, glutamate-1-semialdehyde
      aminomutase. Our data reveal an active-site "gating loop," which undergoes a
      dramatic conformational change during catalysis, that is simultaneously open in
      one subunit and closed in the other. This loop movement requires a beta-sheet-to
      alpha-helix transition to assume the closed conformation, thus facilitating
      transport of substrate toward, and concomitantly forming, an integral part of the
      active site. The accompanying intersubunit cross-talk, which controls negative
      cooperativity between the allosteric pair, was explored at the atomic level. The
      central elements of the communication triad are the cofactor bound to different
      catalytic intermediates, the interface helix, and the gating loop. Together, they
      form a molecular switch in which the cofactor acts as a central signal
      transmitter linking the subunit interface with the gating loop.

PMID- 16954187
TI  - Estimating the diversity of dinosaurs.
AB  - Despite current interest in estimating the diversity of fossil and extant groups,
      little effort has been devoted to estimating the diversity of dinosaurs. Here we
      estimate the diversity of nonavian dinosaurs at approximately 1,850 genera,
      including those that remain to be discovered. With 527 genera currently
      described, at least 71% of dinosaur genera thus remain unknown. Although known
      diversity declined in the last stage of the Cretaceous, estimated diversity was
      steady, suggesting that dinosaurs as a whole were not in decline in the 10
      million years before their ultimate extinction. We also show that known diversity
      is biased by the availability of fossiliferous rock outcrop. Finally, by using a
      logistic model, we predict that 75% of discoverable genera will be known within
      60-100 years and 90% within 100-140 years. Because of nonrandom factors affecting
      the process of fossil discovery (which preclude the possibility of computing
      realistic confidence bounds), our estimate of diversity is likely to be a lower
      bound.

PMID- 16954188
TI  - Cyclobutane pyrimidine dimers are predominant DNA lesions in whole human skin
      exposed to UVA radiation.
AB  - Solar UV radiation is the most important environmental factor involved in the
      pathogenesis of skin cancers. The well known genotoxic properties of UVB
      radiation (290-320 nm) mostly involve bipyrimidine DNA photoproducts. In
      contrast, the contribution of more-abundant UVA radiation (320-400 nm) that are
      not directly absorbed by DNA remains poorly understood in skin. Using a highly
      accurate and quantitative assay based on HPLC coupled with tandem mass
      spectrometry, we determined the type and the yield of formation of DNA damage in
      whole human skin exposed to UVB or UVA. Cyclobutane pyrimidine dimers, a typical
      UVB-induced DNA damage, were found to be produced in significant yield also in
      whole human skin exposed to UVA through a mechanism different from that triggered
      by UVB. Moreover, the latter class of photoproducts is produced in a larger
      amount than 8-oxo-7,8-dihydro-2'-deoxyguanosine, the most common oxidatively
      generated lesion, in human skin. Strikingly, the rate of removal of UVA-generated
      cyclobutane pyrimidine dimers was lower than those produced by UVB irradiation of
      skin. Finally, we compared the formation yields of DNA damage in whole skin with
      those determined in primary cultures of keratinocytes isolated from the same
      donors. We thus showed that human skin efficiently protects against UVB-induced
      DNA lesions, whereas very weak protection is afforded against UVA. These
      observations emphasize the likely role played by the UVA-induced DNA damage in
      skin carcinogenesis and should have consequences for photoprotection strategies.

PMID- 16954189
TI  - Diverse responses of phenology to global changes in a grassland ecosystem.
AB  - Shifting plant phenology (i.e., timing of flowering and other developmental
      events) in recent decades establishes that species and ecosystems are already
      responding to global environmental change. Earlier flowering and an extended
      period of active plant growth across much of the northern hemisphere have been
      interpreted as responses to warming. However, several kinds of environmental
      change have the potential to influence the phenology of flowering and primary
      production. Here, we report shifts in phenology of flowering and canopy greenness
      (Normalized Difference Vegetation Index) in response to four experimentally
      simulated global changes: warming, elevated CO(2), nitrogen (N) deposition, and
      increased precipitation. Consistent with previous observations, warming
      accelerated both flowering and greening of the canopy, but phenological responses
      to the other global change treatments were diverse. Elevated CO(2) and N addition
      delayed flowering in grasses, but slightly accelerated flowering in forbs. The
      opposing responses of these two important functional groups decreased their
      phenological complementarity and potentially increased competition for limiting
      soil resources. At the ecosystem level, timing of canopy greenness mirrored the
      flowering phenology of the grasses, which dominate primary production in this
      system. Elevated CO(2) delayed greening, whereas N addition dampened the
      acceleration of greening caused by warming. Increased precipitation had no
      consistent impacts on phenology. This diversity of phenological changes, between
      plant functional groups and in response to multiple environmental changes, helps
      explain the diversity in large-scale observations and indicates that changing
      temperature is only one of several factors reshaping the seasonality of ecosystem
      processes.

PMID- 16954190
TI  - Engineering RNA sequence specificity of Pumilio repeats.
AB  - Puf proteins bind RNA sequence specifically and regulate translation and
      stability of target mRNAs. A "code" for RNA recognition has been deduced from
      crystal structures of the Puf protein, human Pumilio1, where each of eight
      repeats binds an RNA base via a combination of three side chains at conserved
      positions. Here, we report the creation of seven soluble mutant proteins with
      predictably altered sequence specificity, including one that binds tightly to
      adenosine-uracil-rich element RNA. These data show that Pumilio1 can be used as a
      scaffold to engineer RNA-binding proteins with designed sequence specificity.

PMID- 16954191
TI  - Structural basis for ligand promiscuity in cytochrome P450 3A4.
AB  - Cytochrome P450 (CYP) 3A4 is the most promiscuous of the human CYP enzymes and
      contributes to the metabolism of approximately 50% of marketed drugs. It is also
      the isoform most often involved in unwanted drug-drug interactions. A better
      understanding of the molecular mechanisms governing CYP3A4-ligand interaction
      therefore would be of great importance to any drug discovery effort. Here, we
      present crystal structures of human CYP3A4 in complex with two well characterized
      drugs: ketoconazole and erythromycin. In contrast to previous reports, the
      protein undergoes dramatic conformational changes upon ligand binding with an
      increase in the active site volume by >80%. The structures represent two distinct
      open conformations of CYP3A4 because ketoconazole and erythromycin induce
      different types of coordinate shifts. The binding of two molecules of
      ketoconazole to the CYP3A4 active site and the clear indication of multiple
      binding modes for erythromycin has implications for the interpretation of the
      atypical kinetic data often displayed by CYP3A4. The extreme flexibility revealed
      by the present structures also challenges any attempt to apply computational
      design tools without the support of relevant experimental data.

PMID- 16954192
TI  - Therapeutic potential of histamine H3 receptor agonist for the treatment of
      obesity and diabetes mellitus.
AB  - Histamine H3 receptors (H3Rs) are located on the presynaptic membranes and cell
      soma of histamine neurons, where they negatively regulate the synthesis and
      release of histamine. In addition, H3Rs are also located on nonhistaminergic
      neurons, acting as heteroreceptors to regulate the releases of other amines such
      as dopamine, serotonin, and norepinephrine. The present study investigated the
      effects of H3R ligands on appetite and body-weight regulation by using WT and H3R
      deficient mice (H3RKO), because brain histamine plays a pivotal role in energy
      homeostasis. The results showed that thioperamide, an H3R inverse agonist,
      increases, whereas imetit, an H3R agonist, decreases appetite and body weight in
      diet-induced obese (DiO) WT mice. Moreover, in DiO WT mice, but not in DiO H3RKO
      mice, imetit reduced fat mass, plasma concentrations of leptin and insulin, and
      hepatic triglyceride content. The anorexigenic effects of imetit were associated
      with a reduction in histamine release, but a comparable reduction in histamine
      release with alpha-fluoromethylhistidine, an inhibitor of histamine synthesis,
      increased appetite. Moreover, the anorexigenic effects of imetit were independent
      of the melanocortin system, because imetit comparably reduced appetite in
      melanocortin 3 and 4 receptor-deficient mice. The results provide roles of H3Rs
      in energy homeostasis and suggest a therapeutic potential for H3R agonists in the
      treatment of obesity and diabetes mellitus.

PMID- 16954193
TI  - Foraging biology predicts food web complexity.
AB  - Food webs, the networks of feeding links between species, are central to our
      understanding of ecosystem structure, stability, and function. One of the key
      aspects of food web structure is complexity, or connectance, the number of links
      expressed as a proportion of the total possible number of links. Connectance
      (complexity) is linked to the stability of webs and is a key parameter in recent
      models of other aspects of web structure. However, there is still no fundamental
      biological explanation for connectance in food webs. Here, we propose that
      constraints on diet breadth, driven by optimal foraging, provide such an
      explanation. We show that a simple diet breadth model predicts highly constrained
      values of connectance as an emergent consequence of individual foraging behavior.
      When combined with features of real food web data, such as taxonomic and trophic
      aggregation and cumulative sampling of diets, the model predicts well the levels
      of connectance and scaling of connectance with species richness, seen in real
      food webs. This result is a previously undescribed synthesis of foraging theory
      and food web theory, in which network properties emerge from the behavior of
      individuals and, as such, provides a mechanistic explanation of connectance
      currently lacking in food web models.

PMID- 16954194
TI  - Swimming efficiency of bacterium Escherichia coli.
AB  - We use measurements of swimming bacteria in an optical trap to determine
      fundamental properties of bacterial propulsion. In particular, we directly
      measure the force required to hold the bacterium in the optical trap and
      determine the propulsion matrix, which relates the translational and angular
      velocity of the flagellum to the torques and forces propelling the bacterium.
      From the propulsion matrix, dynamical properties such as torques, swimming speed,
      and power can be obtained by measuring the angular velocity of the motor. We find
      significant heterogeneities among different individuals even though all bacteria
      started from a single colony. The propulsive efficiency, defined as the ratio of
      the propulsive power output to the rotary power input provided by the motors, is
      found to be approximately 2%, which is consistent with the efficiency predicted
      theoretically for a rigid helical coil.

PMID- 16954195
TI  - Anterior cingulate cortex activity can be independent of response conflict in
      Stroop-like tasks.
AB  - Cognitive control includes the ability to formulate goals and plans of action and
      to follow these while facing distraction. Previous neuroimaging studies have
      shown that the presence of conflicting response alternatives in Stroop-like tasks
      increases activity in dorsal anterior cingulate cortex (ACC), suggesting that the
      ACC is involved in cognitive control. However, the exact nature of ACC function
      is still under debate. The prevailing conflict detection hypothesis maintains
      that the ACC is involved in performance monitoring. According to this view, ACC
      activity reflects the detection of response conflict and acts as a signal that
      engages regulative processes subserved by lateral prefrontal brain regions. Here,
      we provide evidence from functional MRI that challenges this view and favors an
      alternative view, according to which the ACC has a role in regulation itself.
      Using an arrow-word Stroop task, subjects responded to incongruent, congruent,
      and neutral stimuli. A critical prediction made by the conflict detection
      hypothesis is that ACC activity should be increased only when conflicting
      response alternatives are present. Our data show that ACC responses are larger
      for neutral than for congruent stimuli, in the absence of response conflict. This
      result demonstrates the engagement of the ACC in regulation itself. A
      computational model of Stroop-like performance instantiating a version of the
      regulative hypothesis is shown to account for our findings.

PMID- 16954196
TI  - A malleable catalyst dominates the metabolism of drugs.

PMID- 16954197
TI  - Effective cell and gene therapy in a murine model of Gaucher disease.
AB  - Gaucher disease (GD) is a lysosomal storage disorder due to an inherited
      deficiency in the enzyme glucosylceramidase (GCase) that causes
      hepatosplenomegaly, cytopenias, and bone disease as key clinical symptoms.
      Previous mouse models with GCase deficiency have been lethal in the perinatal
      period or viable without displaying the clinical features of GD. We have
      generated viable mice with characteristic clinical symptoms of type 1 GD by
      conditionally deleting GCase exons 9-11 upon postnatal induction. Both
      transplantation of WT bone marrow (BM) and gene therapy through retroviral
      transduction of BM from GD mice prevented development of disease and corrected an
      already established GD phenotype. The gene therapy approach generated
      considerably higher GCase activity than transplantation of WT BM. Strikingly,
      both therapeutic modalities normalized glucosylceramide levels and practically no
      infiltration of Gaucher cells could be observed in BM, spleen, and liver,
      demonstrating correction at 5-6 months after treatment. The findings demonstrate
      the feasibility of gene therapy for type 1 GD in vivo. Our type 1 GD mice will
      serve as an excellent tool in the continued efforts toward development of safe
      and efficient cell and gene therapy for type 1 GD.

PMID- 16954199
TI  - Helix-packing motifs in membrane proteins.
AB  - The fold of a helical membrane protein is largely determined by interactions
      between membrane-imbedded helices. To elucidate recurring helix-helix interaction
      motifs, we dissected the crystallographic structures of membrane proteins into a
      library of interacting helical pairs. The pairs were clustered according to their
      three-dimensional similarity (rmsd </=1.5 A), allowing 90% of the library to be
      assigned to clusters consisting of at least five members. Surprisingly, three
      quarters of the helical pairs belong to one of five tightly clustered motifs
      whose structural features can be understood in terms of simple principles of
      helix-helix packing. Thus, the universe of common transmembrane helix-pairing
      motifs is relatively simple. The largest cluster, which comprises 29% of the
      library members, consists of an antiparallel motif with left-handed packing
      angles, and it is frequently stabilized by packing of small side chains occurring
      every seven residues in the sequence. Right-handed parallel and antiparallel
      structures show a similar tendency to segregate small residues to the helix-helix
      interface but spaced at four-residue intervals. Position-specific sequence
      propensities were derived for the most populated motifs. These structural and
      sequential motifs should be quite useful for the design and structural prediction
      of membrane proteins.

PMID- 16954198
TI  - LPS-induced TNF-alpha factor (LITAF)-deficient mice express reduced LPS-induced
      cytokine: Evidence for LITAF-dependent LPS signaling pathways.
AB  - Previously we identified a transcription factor, LPS-Induced TNF-alpha Factor
      (LITAF), mediating inflammatory cytokine expression in LPS-induced processes. To
      characterize the role of LITAF in vivo, we generated a macrophage-specific LITAF
      deficient mouse (macLITAF(-/-)). Our data demonstrate that in macrophages (i)
      several cytokines (such as TNF-alpha, IL-6, sTNF-RII, and CXCL16) are induced at
      lower levels in macLITAF(-/-) compared with LITAF(+/+) control macrophages; (ii)
      macLITAF(-/-) mice are more resistant to LPS-induced lethality. To further
      identify LITAF signaling pathways, we tested mouse TLR-2(-/-), -4(-/-), and -9(-/
      ) and WT peritoneal macrophages exposed to LPS. Using these cells, we now show
      that LITAF expression can be induced after challenge either with LPS from
      Porphyromonas gingivalis via agonism at TLR-2, or with LPS from Escherichia coli
      via agonism at TLR-4, both requiring functional MyD88. We also show that, in
      response to LPS, the MyD88-dependent LITAF pathway differs from the NF-kappaB
      pathway. Furthermore, using a kinase array, p38alpha was found to mediate LITAF
      phosphorylation and the inhibition of p38alpha with a p38-specific inhibitor
      (SB203580) blocked LITAF nuclear translocation and reduced LPS-induced TNF-alpha
      protein levels. Finally, macLITAF(-/-) macrophages rescued by LITAF cDNA
      transfection restored levels of TNF-alpha similar to those observed in WT cells.
      We conclude that LITAF is an important mediator of the LPS-induced inflammatory
      response that can be distinguished from NF-kappaB pathway and that p38alpha is
      the specific kinase involved in the pathway linking LPS/MyD88/LITAF to TNF.

PMID- 16954200
TI  - Revisiting the photochemistry of solar UVA in human skin.

PMID- 16954201
TI  - Realization of a four-step molecular switch in scanning tunneling microscope
      manipulation of single chlorophyll-a molecules.
AB  - Single chlorophyll-a molecules, a vital resource for the sustenance of life on
      Earth, have been investigated by using scanning tunneling microscope manipulation
      and spectroscopy on a gold substrate at 4.6 K. Chlorophyll-a binds on Au(111) via
      its porphyrin unit while the phytyl-chain is elevated from the surface by the
      support of four CH(3) groups. By injecting tunneling electrons from the scanning
      tunneling microscope tip, we are able to bend the phytyl-chain, which enables the
      switching of four molecular conformations in a controlled manner. Statistical
      analyses and structural calculations reveal that all reversible switching
      mechanisms are initiated by a single tunneling-electron energy-transfer process,
      which induces bond rotation within the phytyl-chain.

PMID- 16954202
TI  - Antibody evolution constrains conformational heterogeneity by tailoring protein
      dynamics.
AB  - The evolution of proteins with novel function is thought to start from precursor
      proteins that are conformationally heterogeneous. The corresponding genes may be
      duplicated and then mutated to select and optimize a specific conformation.
      However, testing this idea has been difficult because of the challenge of
      quantifying protein flexibility and conformational heterogeneity as a function of
      evolution. Here, we report the characterization of protein heterogeneity and
      dynamics as a function of evolution for the antifluorescein antibody 4-4-20.
      Using nonlinear laser spectroscopy, surface plasmon resonance, and molecular
      dynamics simulations, we demonstrate that evolution localized the Ab-combining
      site from a heterogeneous ensemble of conformations to a single conformation by
      introducing mutations that act cooperatively and over significant distances to
      rigidify the protein. This study demonstrates how protein dynamics may be
      tailored by evolution and has important implications for our understanding of how
      novel protein functions are evolved.

PMID- 16954203
TI  - Glutamine-dependent NAD+ synthetase. How a two-domain, three-substrate enzyme
      avoids waste.
AB  - Glutamine-dependent NAD(+) synthetase, Qns1, utilizes a glutamine
      aminotransferase domain to supply ammonia for amidation of nicotinic acid adenine
      dinucleotide (NaAD(+)) to NAD(+). Earlier characterization of Qns1 suggested that
      glutamine consumption exceeds NAD(+) production by 40%. To explore whether Qns1
      is systematically wasteful or whether additional features account for this
      behavior, we performed a careful kinetic and molecular genetic analysis. In fact,
      Qns1 possesses remarkable properties to reduce waste. The glutaminase active site
      is stimulated by NaAD(+) more than 50-fold such that glutamine is not appreciably
      consumed in the absence of NaAD(+). Glutamine consumption exceeds NAD(+)
      production over the whole range of glutamine and NaAD(+) substrate concentrations
      with greatest efficiency occurring at saturation of both substrates. Kinetic data
      coupled with site-directed mutagenesis of amino acids in the predicted ammonia
      channel indicate that NaAD(+) stimulates the glutaminase active site in the
      k(cat) term by a synergistic mechanism that does not require ammonia utilization
      by the NaAD(+) substrate. Six distinct classes of Qns1 mutants that fall within
      the glutaminase domain and the synthetase domain selectively inhibit components
      of the coordinated reaction.

PMID- 16954204
TI  - Derlin-1 promotes the efficient degradation of the cystic fibrosis transmembrane
      conductance regulator (CFTR) and CFTR folding mutants.
AB  - A complex involving Derlin-1 and p97 mediates the retrotranslocation and
      endoplasmic reticulum (ER)-associated degradation of misfolded proteins in yeast
      and is used by certain viruses to promote host cell protein degradation (Romisch,
      K. (2005) Annu. Rev. Cell Dev. Biol. 21, 435-456; Lilley, B. N., and Ploegh, H.
      L. (2004) Nature 429, 834-840; Ye, Y., Shibata, Y., Yun, C., Ron, D., and
      Rapoport, T. A. (2004) Nature 429, 841-847). We asked whether the components of
      this pathway are involved in the endoplasmic reticulum-associated degradation of
      the mammalian integral membrane protein, the cystic fibrosis transmembrane
      conductance regulator (CFTR), a substrate for the ubiquitin-proteasome system. We
      report that Derlin-1 and p97 formed complexes with CFTR in human airway
      epithelial cells. Derlin-1 interacted with nonubiquitylated CFTR, whereas p97
      associated with ubiquitylated CFTR. Exogenous expression of Derlin-1 led to its
      co-localization with CFTR in the ER where it reduced wild type (WT) CFTR
      expression and efficiently degraded the disease-associated CFTR folding mutants,
      DeltaF508 and G85E (>90%). Consistent with this, Derlin-1 also reduced the amount
      of WT or DeltaF508 CFTR appearing in detergent-in-soluble aggregates. An
      approximately 70% knockdown of endogenous Derlin-1 by RNA interference increased
      the steady-state levels of WT and DeltaF508 CFTR by 10-15-fold, reflecting its
      significant role in CFTR degradation. Derlin-1 mediated the degradation of N
      terminal CFTR fragments corresponding to the first transmembrane domain of CFTR,
      but CFTR fragments that incorporated additional domains were degraded less
      efficiently. These findings suggest that Derlin-1 recognizes misfolded,
      nonubiquitylated CFTR to initiate its dislocation and degradation early in the
      course of CFTR biogenesis, perhaps by detecting structural instability within the
      first transmembrane domain.

PMID- 16954205
TI  - Coordinated regulation of the Neisseria gonorrhoeae-truncated denitrification
      pathway by the nitric oxide-sensitive repressor, NsrR, and nitrite-insensitive
      NarQ-NarP.
AB  - Neisseria gonorrhoeae survives anaerobically by reducing nitrite to nitrous oxide
      catalyzed by the nitrite and nitric oxide reductases, AniA and NorB. P(aniA) is
      activated by FNR (regulator of fumarate and nitrate reduction), the two-component
      regulatory system NarQ-NarP, and induced by nitrite; P(norB) is induced by NO
      independently of FNR by an uncharacterized mechanism. We report the results of
      microarray analysis, bioinformatic analysis, and chromatin immunoprecipitation,
      which revealed that only five genes with readily identified NarP-binding sites
      are differentially expressed in narP(+) and narP strains. These include three
      genes implicated in the truncated gonococcal denitrification pathway: aniA, norB,
      and narQ. We also report that (i) nitrite induces aniA transcription in a narP
      mutant; (ii) nitrite induction involves indirect inactivation by nitric oxide of
      a gonococcal repressor, NsrR, identified from a multigenome bioinformatic study;
      (iii) in an nsrR mutant, aniA, norB, and dnrN (encoding a putative reactive
      nitrogen species response protein) were expressed constitutively in the absence
      of nitrite, suggesting that NsrR is the only NO-sensing transcription factor in
      N. gonorrhoeae; and (iv) NO rather than nitrite is the ligand to which NsrR
      responds. When expressed in Escherichia coli, gonococcal NarQ and chimaeras of E.
      coli and gonococcal NarQ are ligand-insensitive and constitutively active: a
      "locked-on" phenotype. We conclude that genes involved in the truncated
      denitrification pathway of N. gonorrhoeae are key components of the small NarQP
      regulon, that NarP indirectly regulates P(norB) by stimulating NO production by
      AniA, and that NsrR plays a critical role in enabling gonococci to evade NO
      generated as a host defense mechanism.

PMID- 16954206
TI  - Germ cell nuclear factor is a repressor of CRIPTO-1 and CRIPTO-3.
AB  - The pluripotency of embryonic stem and embryonic carcinoma cells is maintained by
      the expression of a set of "stemness" genes. Whereas these genes are down
      regulated upon induction of differentiation, the germ cell nuclear factor (GCNF)
      is transiently up-regulated and represses several pluripotency genes. CRIPTO-1, a
      co-receptor for the morphogen nodal, is strongly expressed in undifferentiated
      cells and is rapidly down-regulated during retinoic acid-induced differentiation.
      Although CRIPTO-1 is expressed at very low levels in adult tissues under normal
      conditions, it is found highly expressed in a broad range of tumors, where it
      acts as a potent oncogene. We show that expression of CRIPTO-1 is directly
      repressed by GCNF during differentiation of the human teratocarcinoma cell line,
      NT2. GCNF bound to a DR0 element of the CRIPTO-1 promoter in vitro, as shown by
      electrophoretic mobility shift assays, and in vivo, as demonstrated by chromatin
      immunoprecipitation. Reporter gene assays demonstrated that GCNF-mediated
      repression of the CRIPTO-1 promoter is dependent upon the DR0 site.
      Overexpression of GCNF in NT2 cells resulted in repression of CRIPTO-1
      transcription, whereas expression of the transcription-activating fusion
      construct GCNF-VP16 led to an induction of the CRIPTO-1 gene and prevented its
      retinoic acid-induced down-regulation. Furthermore, we demonstrated that CRIPTO
      3, a processed pseudogene of CRIPTO-1 on the X chromosome, is expressed in
      undifferentiated NT2 cells and is regulated by GCNF in parallel to CRIPTO-1.
      Thus, our study supports the hypothesis of GCNF playing a central role during
      differentiation of stem cells by repression of stem cell-specific genes.

PMID- 16954207
TI  - Anthrax edema factor, voltage-dependent binding to the protective antigen ion
      channel and comparison to LF binding.
AB  - Anthrax toxin complex consists of three different molecules, the binding
      component protective antigen (PA, 83 kDa), and the enzymatic components lethal
      factor (LF, 90 kDa) and edema factor (EF, 89 kDa). The 63-kDa N-terminal part of
      PA, PA(63), forms a heptameric channel that inserts at low pH in endosomal
      membranes and that is necessary to translocate EF and LF in the cytosol of the
      target cells. EF is an intracellular active enzyme, which is a calmodulin
      dependent adenylate cyclase (89 kDa) that causes a dramatic increase of
      intracellular cAMP level. Here, the binding of full-length EF on heptameric
      PA(63) channels was studied in experiments with artificial lipid bilayer
      membranes. Full-length EF blocks the PA(63) channels in a dose, temperature,
      voltage, and ionic strength-dependent way with half-saturation constants in the
      nanomolar concentration range. EF only blocked the PA(63) channels when PA(63)
      and EF were added to the same side of the membrane, the cis side. Decreasing
      ionic strength and increasing transmembrane voltage at the cis side of the
      membranes resulted in a strong decrease of the half-saturation constant for EF
      binding. This result suggests that ion-ion interactions are involved in EF
      binding to the PA heptamer. Increasing temperature resulted in increasing half
      saturation constants for EF binding to the PA(63) channels. The binding
      characteristics of EF to the PA(63) channels are compared with those of LF
      binding. The comparison exhibits similarities but also remarkable differences
      between the bindings of both toxins to the PA(63) channel.

PMID- 16954208
TI  - The molecular basis of RhoA specificity in the guanine nucleotide exchange factor
      PDZ-RhoGEF.
AB  - The Dbl homology nucleotide exchange factors (GEFs) activate Rho family cytosolic
      GTPases in a variety of physiological and pathophysiological events. These
      signaling molecules typically act downstream of tyrosine kinase receptors and
      often facilitate nucleotide exchange on more than one member of the Rho GTPase
      superfamily. Three unique GEFs, i.e. p115, PDZ-RhoGEF, and LARG, are activated by
      the G-protein coupled receptors via the Galpha(12/13), and exhibit very selective
      activation of RhoA, although the mechanism by which this is accomplished is not
      fully understood. Based on the recently solved crystal structure of the DH-PH
      tandem of PDZ-RhoGEF in complex with RhoA (Derewenda, U., Oleksy, A., Stevenson,
      A. S., Korczynska, J., Dauter, Z., Somlyo, A. P., Otlewski, J., Somlyo, A. V.,
      and Derewenda, Z. S. (2004) Structure (Lond.) 12, 1955-1965), we conducted
      extensive mutational and functional studies of the molecular basis of the RhoA
      selectivity in PDZ-RhoGEF. We show that while Trp(58) of RhoA is intimately
      involved in the interaction with the DH domain, it is not a selectivity
      determinant, and its interaction with PDZ-RhoGEF is unfavorable. The key
      selectivity determinants are dominated by polar contacts involving residues
      unique to RhoA. We find that selectivity for RhoA versus Cdc42 is defined by a
      small number of interactions.

PMID- 16954209
TI  - Demonstration of lysosomal localization for the mammalian ependymin-related
      protein using classical approaches combined with a novel density shift method.
AB  - Most newly synthesized soluble lysosomal proteins are delivered to the lysosome
      via the mannose 6-phosphate (Man-6-P)-targeting pathway. The presence of the Man
      6-P post-translational modification allows these proteins to be affinity-purified
      on immobilized Man-6-P receptors. This approach has formed the basis for a number
      of proteomic studies that identified multiple as yet uncharacterized Man-6-P
      glycoproteins that may represent new lysosomal proteins. Although the presence of
      Man-6-P is suggestive of lysosomal function, the subcellular localization of such
      candidates requires experimental verification. Here, we have investigated one
      such candidate, ependymin-related protein (EPDR). EPDR is a protein of unknown
      function with some sequence similarity to ependymin, a fish protein thought to
      play a role in memory consolidation and learning. Using classical subcellular
      fractionation on rat brain, EPDR co-distributes with lysosomal proteins, but
      there is significant overlap between lysosomal and mitochondrial markers. For
      more definitive localization, we have developed a novel approach based upon a
      selective buoyant density shift of the brain lysosomes in a mutant mouse lacking
      NPC2, a lysosomal protein involved in lipid transport. EPDR, in parallel with
      lysosomal markers, shows this density shift in gradient centrifugation
      experiments comparing mutant and wild type mice. This approach, combined with
      morphological analyses, demonstrates that EPDR resides in the lysosome. In
      addition, the lipidosis-induced density shift approach represents a valuable tool
      for identification and validation of both luminal and membrane lysosomal proteins
      that should be applicable to high throughput proteomic studies.

PMID- 16954210
TI  - Structural basis and functional consequence of Helicobacter pylori CagA
      multimerization in cells.
AB  - Helicobacter pylori cagA-positive strains are associated with gastric
      adenocarcinoma. The cagA gene product CagA is delivered into gastric epithelial
      cells where it localizes to the plasma membrane and undergoes tyrosine
      phosphorylation at the EPIYA-repeat region, which contains the EPIYA-A segment,
      EPIYA-B segment, and Western CagA-specific EPIYA-C or East Asian CagA-specific
      EPIYA-D segment. In host cells, CagA specifically binds to and deregulates SHP-2
      phosphatase via the tyrosine-phosphorylated EPIYA-C or EPIYA-D segment, thereby
      inducing an elongated cell shape known as the hummingbird phenotype. In this
      study, we found that CagA multimerizes in cells in a manner independent of its
      tyrosine phosphorylation. Using a series of CagA mutants, we identified a
      conserved amino acid sequence motif (FPLXRXXXVXDLSKVG), which mediates CagA
      multimerization, within the EPIYA-C segment as well as in a sequence that located
      immediately downstream of the EPIYA-C or EPIYA-D segment. We also found that a
      phosphorylation-resistant CagA, which multimerizes but cannot bind SHP-2,
      inhibits the wild-type CagA-SHP-2 complex formation and abolishes induction of
      the hummingbird phenotype. Thus, SHP-2 binds to a preformed and
      tyrosinephosphorylated CagA multimer via its two Src homology 2 domains. These
      results, in turn, indicate that CagA multimerization is a prerequisite for CagA
      SHP-2 interaction and subsequent deregulation of SHP-2. The present work raises
      the possibility that inhibition of CagA multimerization abolishes
      pathophysiological activities of CagA that promote gastric carcinogenesis.

PMID- 16954211
TI  - Paradoxical striatal cellular signaling responses to psychostimulants in
      hyperactive mice.
AB  - Recent investigations have shown that three major striatal-signaling pathways
      (protein kinase A/DARPP-32, Akt/glycogen synthase kinase 3, and ERK) are involved
      in the regulation of locomotor activity by the monoaminergic neurotransmitter
      dopamine. Here we used dopamine transporter knock-out mice to examine which
      particular changes in the regulation of these cell signaling mechanisms are
      associated with distinct behavioral responses to psychostimulants. In normal
      animals, amphetamine and methylphenidate increase extracellular levels of
      dopamine, leading to an enhancement of locomotor activity. However, in dopamine
      transporter knock-out mice that display a hyperactivity phenotype resulting from
      a persistent hyperdopaminergic state, these drugs antagonize hyperactivity. Under
      basal conditions, dopamine transporter knock-out mice show enhanced striatal
      DARPP-32 phosphorylation, activation of ERK, and inactivation of Akt as compared
      with wild-type littermates. However, administration of amphetamine or
      methylphenidate to these mice reveals that inhibition of ERK signaling is a
      common determinant for the ability of these drugs to antagonize hyperactivity. In
      contrast, psychostimulants activate ERK and induce hyperactivity in normal
      animals. In hyperactive mice psychostimulant-mediated behavioral inhibition and
      ERK regulation are also mimicked by the serotonergic drugs fluoxetine and 5
      carboxamidotryptamine, thereby revealing the involvement of serotonin-dependent
      inhibition of striatal ERK signaling. Furthermore, direct inhibition of the ERK
      signaling cascade in vivo using the MEK inhibitor SL327 recapitulates the actions
      of psychostimulants in hyperactive mice and prevents the locomotor-enhancing
      effects of amphetamine in normal animals. These data suggest that the inhibitory
      action of psychostimulants on dopamine-dependent hyperactivity results from
      altered regulation of striatal ERK signaling. In addition, these results
      illustrate how altered homeostatic state of neurotransmission can influence in
      vivo signaling responses and biological actions of pharmacological agents used to
      manage psychiatric conditions such as Attention Deficit Hyperactivity Disorder
      (ADHD).

PMID- 16954212
TI  - Rat spongiotrophoblast-specific protein is predominantly a unique low sulfated
      chondroitin sulfate proteoglycan.
AB  - We have previously demonstrated that the human placenta contains a uniquely low
      sulfated extracellular aggrecan family chondroitin sulfate proteoglycan (CSPG).
      This CSPG is a major receptor for the adherence of Plasmodium falciparum-infected
      red blood cells (IRBCs) in placentas, causing pregnancy-specific malaria.
      However, it is not known whether such low sulfated CSPGs occur in placentas of
      other animals and, if so, whether IRBCs bind to those CSPGs. In this study, we
      show that rat placenta contains a uniquely low sulfated extracellular CSPG
      bearing chondroitin sulfate (CS) chains, which comprise only approximately 2% 4
      sulfated and the remainder nonsulfated disaccharides. Surprisingly, the core
      protein of the rat placental CSPG, unlike that of the human placental CSPG, is a
      spongiotrophoblast-specific protein (SSP), which is expressed in a pregnancy
      stage-dependent manner. The majority of rat placental SSP is present in the CSPG
      form, and only approximately 10% occurs without CS chain substitution. Of the
      total SSP-CSPG in rat placenta, approximately 57% is modified with a single CS
      chain, and approximately 43% carries two CS chains. These data together with the
      previous finding on human placental CSPG suggest that the expression of low
      sulfated CSPG is a common feature of animal placentas. Our data also show that
      the unique species-specific difference in the biology of the rat and human
      placentas is reflected in the occurrence of completely different CSPG core
      protein types. Furthermore, the rat SSP-CSPG binds P. falciparum IRBCs in a CS
      chain-dependent manner. Since IRBCs have been reported to accumulate in the
      placentas of malaria parasite-infected rodents, our results have important
      implications for exploiting pregnant rats as a model for studying chondroitin 4
      sulfate-based therapeutics for human placental malaria.

PMID- 16954213
TI  - Activation of Ras up-regulates pro-apoptotic BNIP3 in nitric oxide-induced cell
      death.
AB  - Nitric oxide (NO) produced by NO synthases causes nitration and nitrosylation of
      cellular factors. We have shown previously that endogenously produced or
      exogenously added NO induces expression of BNIP3 (Bcl-2/adenovirus E1B 19 kDa
      interacting protein 3), leading to death of macrophages (Yook, Y.-H., Kang, K.
      H., Maeng, O., Kim, T.-R., Lee, J.-O., Kang, K.-i., Kim, Y.-S., Paik, S.-G., and
      Lee, H. (2004) Biochem. Biophys. Res. Commun. 321, 298-305). We now provide
      evidence that Ras mediates NO-induced BNIP3 expression via the MEK/ERK/hypoxia
      inducible factor (HIF)-1 pathway. (a) ras-Q61L, a constitutively active form of
      Ras, up-regulated BNIP3 protein expression by enhancing Bnip3 promoter activity,
      and ras-S17N, a dominant-negative form, and ras-C118S, an S-nitrosylation mutant,
      blocked NO-induced BNIP3 expression, suggesting that Ras acts downstream of NO
      and that NO activates Ras by nitrosylation. (b) U0126, a specific MEK inhibitor,
      completely abolished BNIP3 expression and the stimulation of promoter activity by
      NO and Ras, whereas 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, SB203580, and
      wortmannin, specific inhibitors of soluble guanylyl cyclase, p38 MAPK, and
      phosphatidylinositol 3-kinase, respectively, had no effect. Ras, MEK1/2, and
      ERK1/2 were sequentially activated by NO treatment of macrophages. (c) Mutation
      of the HIF-1-binding site (hypoxia-response element) in the Bnip3 promoter
      abolished BNIP3 induction, and HIF-1alpha was strongly induced by NO. (d)
      Transient expression of activated Ras promoted macrophage death, as did NO, and
      this Ras-mediated cell death was inhibited by silencing BNIP3 expression. These
      results suggest that NO-induced death of macrophages is mediated, at least in
      part, by BNIP3 induction.

PMID- 16954214
TI  - GABA increases both the conductance and mean open time of recombinant GABAA
      channels co-expressed with GABARAP.
AB  - The single channel properties of recombinant gamma-aminobutyric acid type A
      (GABA(A))alphabetagamma receptors co-expressed with the trafficking protein
      GABARAP were investigated using membrane patches in the outside-out patch clamp
      configuration from transiently transfected L929 cells. In control cells
      expressing alphabetagamma receptors alone, GABA activated single channels whose
      main conductance was 30 picosiemens (pS) with a subconductance state of 20 pS,
      and increasing the GABA concentration did not alter their conductance. In
      contrast, when GABA(A) receptors were co-expressed with GABARAP, the GABA
      activated single channels displayed multiple, high conductances (> or =40 pS),
      and GABA (> or =10 microM) was able to increase their conductance, up to a
      maximum of 60 pS. The mean open time of GABA-activated channels in control cells
      expressing alphabetagamma receptors alone was 2.3 +/- 0.1 ms for the main 30-pS
      channel and shorter for the subconductance state (20 pS, 0.8 +/- 0.1 ms). Similar
      values were measured for the 30- and 20-pS channels active in patches from cells
      co-expressing GABARAP. However higher conductance channels (> or =40 pS) remained
      open longer, irrespective of whether GABA or GABA plus diazepam activated them.
      Plotting mean open times against mean conductances revealed a linear relationship
      between these two parameters. Since high GABA concentrations increase both the
      maximum single channel conductance and mean open time of GABA(A) channels co
      expressed with GABARAP, trafficking processes must influence ion channel
      properties. This suggests that the organization of extrasynaptic GABA(A)
      receptors may provide a range of distinct inhibitory currents in the brain and,
      further, provide differential drug responses.

PMID- 16954215
TI  - Crystal structure of thrombin in a self-inhibited conformation.
AB  - The activating effect of Na(+) on thrombin is allosteric and depends on the
      conformational transition from a low activity Na(+)-free (slow) form to a high
      activity Na(+)-bound (fast) form. The structures of these active forms have been
      solved. Recent structures of thrombin obtained in the absence of Na(+) have also
      documented inactive conformations that presumably exist in equilibrium with the
      active slow form. The validity of these inactive slow form structures, however,
      is called into question by the presence of packing interactions involving the
      Na(+) site and the active site regions. Here, we report a 1.87A resolution
      structure of thrombin in the absence of inhibitors and salts with a single
      molecule in the asymmetric unit and devoid of significant packing interactions in
      regions involved in the allosteric slow --> fast transition. The structure shows
      an unprecedented self-inhibited conformation where Trp-215 and Arg-221a relocate
      >10A to occlude the active site and the primary specificity pocket, and the
      guanidinium group of Arg-187 penetrates the protein core to fill the empty Na(+)
      binding site. The extreme mobility of Trp-215 was investigated further with the
      W215P mutation. Remarkably, the mutation significantly compromises cleavage of
      the anticoagulant protein C but has no effect on the hydrolysis of fibrinogen and
      PAR1. These findings demonstrate that thrombin may assume an inactive
      conformation in the absence of Na(+) and that its procoagulant and anticoagulant
      activities are closely linked to the mobility of residue 215.

PMID- 16954216
TI  - The exon 6ABC region of amelogenin mRNA contribute to increased levels of
      amelogenin mRNA through amelogenin protein-enhanced mRNA stabilization.
AB  - We recently demonstrated that the reuptake of full-length amelogenin protein
      results in increased levels of amelogenin mRNA through enhanced mRNA
      stabilization (Xu, L., Harada, H., Tamaki, T. Y., Matsumoto, S., Tanaka, J., and
      Taniguchi, A. (2006) J. Biol. Chem. 281, 2257-2262). Here, we examined the
      molecular mechanism of enhanced amelogenin mRNA stabilization. To identify the
      cis-regulatory region within amelogenin mRNA, we tested various reporter systems
      using a deletion series of reporter plasmids. A deletion at exon 6ABC of
      amelogenin mRNA resulted in a 2.5-fold increase in the amelogenin mRNA expression
      level when compared with that of full-length mRNA, indicating that a cis-element
      exists in exon 6ABC of amelogenin mRNA. Furthermore, Northwestern analysis
      demonstrated that amelogenin protein binds directly to its mRNA in vitro,
      suggesting that amelogenin protein acts as a trans-acting protein that
      specifically binds to this cis-element. Moreover, recombinant mouse amelogenin
      protein extended the half-life of full-length amelogenin mRNA but did not
      significantly alter the half-life of exon 6ABC-deletion mutant mRNA. The splice
      products produced by deletion of exon 6ABC are known as leucine-rich amelogenin
      peptides and have signaling effects on cells. Our findings also suggest that the
      regulation of full-length amelogenin protein expression differs from the
      regulation of leucine-rich amelogenin peptide expression.

PMID- 16954217
TI  - Transcription factor activating enhancer-binding protein-2beta. A negative
      regulator of adiponectin gene expression.
AB  - We previously reported the association between the activating enhancer-binding
      protein-2beta (AP-2beta) transcription factor gene and type 2 diabetes. This gene
      is preferentially expressed in adipose tissue, and subjects with the disease
      susceptible allele of AP-2beta showed stronger expression in adipose tissue than
      those without the susceptible allele. Furthermore, overexpression of AP-2beta
      leads to lipid accumulation by enhancing glucose transport and inducing insulin
      resistance in 3T3-L1 adipocytes. In this study we demonstrated that
      overexpression of AP-2beta in 3T3-L1 adipocytes decreased the expression and
      secretion of adiponectin and increased those of interleukin-6 (IL-6).
      Interestingly, the effects of AP-2beta on the expressions of adiponectin and IL-6
      and the mechanisms by which AP-2beta modulated their expressions were different.
      We found that the promoter activity of adiponectin gene was inhibited by AP-2beta
      overexpression and enhanced by knockdown of endogenous AP-2beta, whereas IL-6 was
      unaffected. Electrophoretic mobility shift assays revealed the existence of
      putative responsive elements for AP-2beta and NF-YA in human and mouse
      adiponectin promoter regions, and mutation of this AP-2beta binding site
      abolished the inhibitory effect of AP-2beta. Furthermore, chromatin
      immunoprecipitation assays demonstrated that AP-2beta and NF-YA competitively
      bind to the same region of the adiponectin promoter. Our results clearly
      demonstrated that AP-2beta directly inhibits adiponectin gene expression by
      displacing NF-YA and binding to its promoter. We conclude that AP-2beta might
      modulate the expression of adiponectin by directly inhibiting its transcriptional
      activity.

PMID- 16954218
TI  - Identification of MAPK phosphorylation sites and their role in the localization
      and activity of hypoxia-inducible factor-1alpha.
AB  - Hypoxia-inducible factor 1 (HIF-1) controls the expression of most genes induced
      by hypoxic conditions. Regulation of expression and activity of its inducible
      subunit, HIF-1alpha, involves several post-translational modifications. To study
      HIF-1alpha phosphorylation, we have used human full-length recombinant HIF-1alpha
      as a substrate in kinase assays. We show that at least two different nuclear
      protein kinases, one of them identified as p42/p44 MAPK, can modify HIF-1alpha.
      Analysis of in vitro phosphorylated HIF-1alpha by mass spectroscopy revealed
      residues Ser-641 and Ser-643 as possible MAPK phosphorylation sites. Site
      directed mutagenesis of these residues reduced significantly the phosphorylation
      of HIF-1alpha. When these mutant forms of HIF-1alpha were expressed in HeLa
      cells, they exhibited much lower transcriptional activity than the wild-type
      form. However, expression of the same mutants in yeast revealed that their
      capacity to stimulate transcription was not significantly compromised.
      Localization of the green fluorescent protein-tagged HIF-1alpha mutants in HeLa
      cells showed their exclusion from the nucleus in contrast to wild-type HIF
      1alpha. Treatment of the cells with leptomycin B, an inhibitor of the major
      exportin CRM1, reversed this exclusion and led to nuclear accumulation and
      partial recovery of the activity of the HIF-1alpha mutants. Moreover, inhibition
      of the MAPK pathway by PD98059 impaired the phosphorylation, nuclear
      accumulation, and activity of wild-type GFP-HIF-1alpha. Overall, these data
      suggest that phosphorylation of Ser-641/643 by MAPK promotes the nuclear
      accumulation and transcriptional activity of HIF-1alpha by blocking its CRM1
      dependent nuclear export.

PMID- 16954219
TI  - Neuronal PAS domain protein 1 is a transcriptional repressor and requires
      arylhydrocarbon nuclear translocator for its nuclear localization.
AB  - Neuronal PAS domain protein 1 (NPAS1), a basic helix-loop-helix-PAS transcription
      factor expressed in the central nervous system, has been suggested to be involved
      in neuronal differentiation. However, relatively little is known about the
      molecular mechanism underlying the role of NPAS1 during development. In this
      study we set out to characterize the different domains within NPAS1. We showed
      that the nuclear localization of NPAS1 is dependent on the presence of ARNT. In
      addition, the transcriptional potential of ARNT is not required for this
      localization. In the absence of ARNT, NPAS1 is excluded from the nucleus, and
      this exclusion is due to the presence of a nuclear export signal within the N
      terminus of NPAS1. The interaction between NPAS1 and ARNT is via their N termini.
      We found no transactivation domain within NPAS1; instead, we mapped out at least
      three repression domains within NPAS1, suggesting that NPAS1 acts as a repressor.
      Furthermore, our experiments showed that NPAS1 is able to repress the
      transactivation functions of ARNT and ARNT2. We suggest that NPAS1 is guided into
      the nucleus by ARNT via the ARNT nuclear localization signal, and NPAS1 can
      override the activation function of adjacent transcription factors, providing a
      mechanism by which NPAS1 may inhibit transcription.

PMID- 16954220
TI  - Invariant Leu preceding turn motif phosphorylation site controls the interaction
      of protein kinase C with Hsp70.
AB  - Heat shock proteins play important roles in regulating signal transduction in
      cells by associating with, and stabilizing, diverse signaling molecules,
      including protein kinases. Previously, we have shown that heat shock protein
      Hsp70 associates with protein kinase C (PKC) via an interaction that is triggered
      by dephosphorylation at the turn phosphorylation motif. Here we have identified
      an invariant residue in the carboxyl terminus of PKC that mediates the binding to
      Hsp70. Specifically, we show that Hsp70 binds to Leu (Leu-640) immediately
      preceding the conserved turn motif autophosphorylation site (Thr-641) in PKC
      betaII. Co-immunoprecipitation experiments reveal that mutation of Leu-640 to Gly
      decreases the interaction of Hsp70 with PKC betaII. This weakened interaction
      between Hsp70 and the mutant PKCs results in accumulation of dephosphorylated PKC
      in the detergent-insoluble fraction of cells. In addition, the Hsp70-binding
      mutant is considerably more sensitive to down-regulation compared with WT PKC:
      disruption of Hsp70 binding leads to accelerated dephosphorylation and enhanced
      ubiquitination of mutant PKC upon phorbol ester treatment. Last, pulse-chase
      experiments demonstrate that Hsp70 preferentially binds the species of mature PKC
      that has become dephosphorylated compared with the newly synthesized protein that
      has yet to be phosphorylated. Thus, Hsp70 binds a hydrophobic residue preceding
      the turn motif, protecting PKC from down-regulation and sustaining the signaling
      lifetime of the kinase.

PMID- 16954221
TI  - Structural basis of neutralization by a human anti-severe acute respiratory
      syndrome spike protein antibody, 80R.
AB  - Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease
      that caused pandemic spread in 2003. The etiological agent of SARS is a novel
      coronavirus (SARS-CoV). The coronaviral surface spike protein S is a type I
      transmembrane glycoprotein that mediates initial host binding via the cell
      surface receptor angiotensin-converting enzyme 2 (ACE2), as well as the
      subsequent membrane fusion events required for cell entry. Here we report the
      crystal structure of the S1 receptor binding domain (RBD) in complex with a
      neutralizing antibody, 80R, at 2.3 A resolution, as well as the structure of the
      uncomplexed S1 RBD at 2.2 A resolution. We show that the 80R-binding epitope on
      the S1 RBD overlaps very closely with the ACE2-binding site, providing a
      rationale for the strong binding and broad neutralizing ability of the antibody.
      We provide a structural basis for the differential effects of certain mutations
      in the spike protein on 80R versus ACE2 binding, including escape mutants, which
      should facilitate the design of immunotherapeutics to treat a future SARS
      outbreak. We further show that the RBD of S1 forms dimers via an extensive
      interface that is disrupted in receptor- and antibody-bound crystal structures,
      and we propose a role for the dimer in virus stability and infectivity.

PMID- 16954222
TI  - Cannabinoid WIN 55,212-2 regulates TRPV1 phosphorylation in sensory neurons.
AB  - Cannabinoids are known to have multiple sites of action in the nociceptive
      system, leading to reduced pain sensation. However, the peripheral mechanism(s)
      by which this phenomenon occurs remains an issue that has yet to be resolved.
      Because phosphorylation of TRPV1 (transient receptor potential subtype V1) plays
      a key role in the induction of thermal hyperalgesia in inflammatory pain models,
      we evaluated whether the cannabinoid agonist WIN 55,212-2 (WIN) regulates the
      phosphorylation state of TRPV1. Here, we show that treatment of primary rat
      trigeminal ganglion cultures with WIN led to dephosphorylation of TRPV1,
      specifically at threonine residues. Utilizing Chinese hamster ovary cell lines,
      we demonstrate that Thr(144) and Thr(370) were dephosphorylated, leading to
      desensitization of the TRPV1 receptor. This post-translational modification
      occurred through activation of the phosphatase calcineurin (protein phosphatase
      2B) following WIN treatment. Furthermore, knockdown of TRPA1 (transient receptor
      potential subtype A1) expression in sensory neurons by specific small interfering
      RNA abolished the WIN effect on TRPV1 dephosphorylation, suggesting that WIN acts
      through TRPA1. We also confirm the importance of TRPA1 in WIN-induced
      dephosphorylation of TRPV1 in Chinese hamster ovary cells through targeted
      expression of one or both receptor channels. These results imply that the
      cannabinoid WIN modulates the sensitivity of sensory neurons to TRPV1 activation
      by altering receptor phosphorylation. In addition, our data could serve as a
      useful strategy in determining the potential use of certain cannabinoids as
      peripheral analgesics.

PMID- 16954223
TI  - betaPak-interacting exchange factor-mediated Rac1 activation requires smgGDS
      guanine nucleotide exchange factor in basic fibroblast growth factor-induced
      neurite outgrowth.
AB  - Neuritogenesis requires active actin cytoskeleton rearrangement in which Rho
      GTPases play a pivotal role. In a previous study (Shin, E. Y., Woo, K. N., Lee,
      C. S., Koo, S. H., Kim, Y. G., Kim, W. J., Bae, C. D., Chang, S. I., and Kim, E.
      G. (2004) J. Biol. Chem. 279, 1994-2004), we demonstrated that betaPak
      interacting exchange factor (betaPIX) guanine nucleotide exchange factor (GEF)
      mediates basic fibroblast growth factor (bFGF)-stimulated Rac1 activation through
      phosphorylation of Ser-525 and Thr-526 at the GIT-binding domain (GBD). However,
      the mechanism by which this phosphorylation event regulates the Rac1-GEF activity
      remained elusive. We show here that betaPIX binds to Rac1 via the GBD and also
      activates the GTPase via an associated GEF, smgGDS, in a phosphorylation
      dependent manner. Notably, the Rac1-GEF activity of betaPIX persisted for an
      extended period of time following bFGF stimulation, unlike other Rho GEFs
      containing the Dbl homology domain. We demonstrate that C-PIX, containing proline
      rich, GBD, and leucine zipper domains can interact with Rac1 via the GBD in vitro
      and in vivo and also mediated bFGF-stimulated Rac1 activation, as determined by a
      modified GEF assay and fluorescence resonance energy transfer analysis. However,
      nonphosphorylatable C-PIX (S525A/T526A) failed to generate Rac1-GTP. Finally,
      betaPIX is shown to form a trimeric complex with smgGDS and Rac1; down-regulation
      of smgGDS expression by short interfering RNA causing significant inhibition of
      betaPIX-mediated Rac1 activation and neurite outgrowth. These results provide
      evidence for a new and unexpected mechanism whereby betaPIX can regulate Rac1
      activity.

PMID- 16954224
TI  - Domain and nucleotide dependence of the interaction between Saccharomyces
      cerevisiae translation elongation factors 3 and 1A.
AB  - Eukaryotic translation elongation factor 3 (eEF3) is a fungal-specific ATPase
      proposed to catalyze the release of deacylated-tRNA from the ribosomal E-site. In
      addition, it has been shown to interact with the aminoacyl-tRNA binding GTPase
      elongation factor 1A (eEF1A), perhaps linking the E and A sites. Domain mapping
      demonstrates that amino acids 775-980 contain the eEF1A binding sites. Domain III
      of eEF1A, which is also involved in actin-related functions, is the site of eEF3
      binding. The binding of eEF3 to eEF1A is enhanced by ADP, indicating the
      interaction is favored post-ATP hydrolysis but is not dependent on the eEF1A
      bound nucleotide. A temperature-sensitive P915L mutant in the eEF1A binding site
      of eEF3 has reduced ATPase activity and affinity for eEF1A. These results support
      the model that upon ATP hydrolysis, eEF3 interacts with eEF1A to help catalyze
      the delivery of aminoacyl-tRNA at the A-site of the ribosome. The dynamics of
      when eEF3 interacts with eEF1A may be part of the signal for transition of the
      post to pre-translocational ribosomal state in yeast.

PMID- 16954225
TI  - Participation of the Lys313-Ile333 sequence of the purinergic P2X4 receptor in
      agonist binding and transduction of signals to the channel gate.
AB  - To study the roles of the Lys(313)-Ile(333) ectodomain sequence of the rat P2X(4)
      receptor in ATP binding and transduction of signals to the channel gate, the
      conserved Lys(313), Tyr(315), Gly(316), Ike(317), Arg(318), Asp(320), Val(323),
      Lys(329), Phe(330), and Ile(333) residues were mutated. Current recordings were
      done on lifted cells and ATP was applied using an ultrafast solution-switching
      system. The rates of wild type channel opening and closing in the presence of
      ATP, but not the rate of washout-induced closing, were dependent on agonist
      concentration. All mutants other than I317A were expressed in the plasma membrane
      at comparable levels. The majority of mutants showed significant changes in the
      peak amplitude of responses and the EC(50) values for ATP. When stimulated with
      the supramaximal (1.4 mm) ATP concentration, mutants also differed in the
      kinetics of their activation, deactivation, and/or desensitization. The results
      suggest a critical role of the Lys(313) residue in receptor function other than
      coordination of the phosphate group of ATP and possible contribution of the
      Tyr(315) residue to the agonist binding module. The pattern of changes of
      receptor function by mutation of other residues was consistent with the operation
      of the Gly(316)-Ile(333) sequence as a signal transduction module between the
      ligand binding domain and the channel gate in the second transmembrane domain.

PMID- 16954226
TI  - The Actin cross-linking domain of the Vibrio cholerae RTX toxin directly
      catalyzes the covalent cross-linking of actin.
AB  - Vibrio cholerae is a Gram-negative bacterial pathogen that exports enterotoxins
      to alter host cells and to elicit diarrheal disease. Among the secreted toxins is
      the multifunctional RTX toxin, which causes cell rounding and actin
      depolymerization by covalently cross-linking actin monomers into dimers, trimers,
      and higher multimers. The region of the toxin responsible for cross-linking
      activity is the actin cross-linking domain (ACD). In this study, we further
      investigated the role of the ACD in the actin cross-linking reaction. We show
      that the RTX toxin cross-links actin independently of tissue transglutaminase,
      thus eliminating an indirect model of ACD activity. We demonstrate that a fusion
      protein of the ACD and the N-terminal portion of lethal factor from Bacillus
      anthracis (LF(N)ACD) has cross-linking activity in vivo and in crude cell
      extracts. Furthermore, we determined that LF(N)ACD directly catalyzes the
      formation of covalent linkages between actin molecules in vitro and that Mg(2+)
      and ATP are essential cofactors for the cross-linking reaction. In addition, G
      actin is proposed as a cytoskeletal substrate of the RTX toxin in vivo. Future
      studies of the in vitro cross-linking reaction will facilitate characterization
      of the enzymatic properties of the ACD and contribute to our knowledge of the
      novel mechanism of covalent actin cross-linking.

PMID- 16954227
TI  - Genetic variability in the G protein gene of group A and B respiratory syncytial
      viruses from India.
AB  - Respiratory syncytial virus (RSV) is the most commonly identified viral agent of
      acute respiratory tract infection (ARI) of young children and causes repeat
      infections throughout life. Limited data are available on the molecular
      epidemiology of RSV from developing countries, including India. This study
      reports on the genetic variability in the glycoprotein G gene among RSV isolates
      from India. Reverse transcription-PCR for a region of the RSV G protein gene was
      done with nasopharyngeal aspirates (NPAs) collected in a prospective longitudinal
      study in two rural villages near Delhi and from children with ARI seen in an
      urban hospital. Nucleotide sequence comparisons among 48 samples demonstrated a
      higher prevalence of group A (77%) than group B (23%) RSV isolates. The level of
      genetic variability was higher among the group A viruses (up to 14%) than among
      the group B viruses (up to 2%). Phylogenetic analysis revealed that both the GA2
      and GA5 group A RSV genotypes were prevalent during the 2002-2003 season and that
      genotype GA5 was predominant in the 2003-2004 season, whereas during the 2004
      2005 season both genotype GA5 and genotype BA, a newly identified group B
      genotype, cocirculated in almost equal proportions. Comparison of the
      nonsynonymous mutation-to-synonymous mutation ratios (dN/dS) revealed greater
      evidence for selective pressure between the GA2 and GA5 genotypes (dN/dS, 1.78)
      than within the genotypes (dN/dS, 0.69). These are among the first molecular
      analyses of RSV strains from the second most populous country in the world and
      will be useful for comparisons to candidate vaccine strains.

PMID- 16954228
TI  - Development of an internal positive control for rapid diagnosis of avian
      influenza virus infections by real-time reverse transcription-PCR with
      lyophilized reagents.
AB  - We developed an internal positive control (IPC) RNA to help ensure the accuracy
      of the detection of avian influenza virus (AIV) RNA by reverse transcription (RT)
      PCR and real-time RT-PCR (RRT-PCR). The IPC was designed to have the same binding
      sites for the forward and reverse primers of the AIV matrix gene as the target
      amplicon, but it had a unique internal sequence used for the probe site. The
      amplification of the viral RNA and the IPC by RRT-PCR were monitored with two
      different fluorescent probes in a multiplex format, one specific for the AIV
      matrix gene and the other for the IPC. The RRT-PCR test was further simplified
      with the use of lyophilized bead reagents for the detection of AIV RNA. The RRT
      PCR with the bead reagents was more sensitive than the conventional wet reagents
      for the detection of AIV RNA. The IPC-based RRT-PCR detected inhibitors in blood,
      kidney, lungs, spleen, intestine, and cloacal swabs, but not allantoic fluid,
      serum, or tracheal swabs The accuracy of RRT-PCR test results with the
      lyophilized beads was tested on cloacal and tracheal swabs from experimental
      birds inoculated with AIV and compared with virus isolation (VI) on embryonating
      chicken eggs. There was 97 to 100% agreement of the RRT-PCR test results with VI
      for tracheal swabs and 81% agreement with VI for cloacal swabs, indicating a high
      level of accuracy of the RRT-PCR assay. The same IPC in the form of armored RNA
      was also used to monitor the extraction of viral RNA and subsequent detection by
      RRT-PCR.

PMID- 16954229
TI  - Edema disease caused by a clone of Escherichia coli O147.
AB  - Edema disease is a systemic disease of weaned pigs caused by host-adapted strains
      of Escherichia coli, most commonly belonging to serogroup O138, O139, or O141. In
      the late 1990s, E. coli O147 strains containing the virulence genes f18, sta,
      stb, and stx(2) were recovered from outbreaks of edema disease in the United
      States. Pulsed-field gel electrophoresis (PFGE) was used to determine that the
      majority of these strains (34/43) were closely related to one another. Subsequent
      analysis by multilocus restriction typing confirmed the PFGE results and
      indicated that the cluster of edema disease strains were only distantly related
      to other E. coli O147 strains. Serogrouping of edema disease isolates from the
      Iowa State University Veterinary Diagnostic laboratory recovered between 1996 and
      2000 indicated that 42% belonged to serogroup O147. Our data suggest that these
      strains may be a common serotype of edema disease-causing E. coli in the United
      States.

PMID- 16954230
TI  - Molecular epidemiology of oral treponemes in patients with periodontitis and in
      periodontitis-resistant subjects.
AB  - The etiologic role of oral treponemes in human periodontitis is still under
      debate. Although seen by dark-field microscopy in large numbers, their possible
      role is still unclear since they comprise some 60 different phylotypes, most of
      which are still uncultured. To determine their status as mere commensals or
      opportunistic pathogens, molecular epidemiological studies are required that
      include both cultured and as-yet-uncultured organisms. Here we present such data,
      comparing treponemal populations from chronic periodontitis (CP) or generalized
      aggressive periodontitis (GAP) patients. As a periodontitis-resistant (PR)
      control group, we included elderly volunteers with more than 20 natural teeth and
      no history of periodontal treatment and no or minimal clinical signs of
      periodontitis. Almost every treponemal phylotype was present in all three groups.
      For most treponemes, the proportion of subjects positive for a certain species or
      phylotype was higher in both periodontitis groups than in the PR group. This
      difference was pronounced for treponemes of the phylogenetic groups II and IV and
      for Treponema socranskii and Treponema lecithinolyticum. Between the
      periodontitis groups the only significant differences were seen for T. socranskii
      and T. lecithinolyticum, which were found more often in periodontal pockets of
      GAP patients than of CP patients. In contrast, no difference was found for
      Treponema denticola. Our findings, however, strengthen the hypothesis of
      treponemes being opportunistic pathogens. It appears that T. socranskii, T.
      lecithinolyticum and group II and IV treponemes may represent good indicators for
      periodontitis and suggest the value of the respective probes for microbiological
      diagnosis in periodontitis subjects.

PMID- 16954231
TI  - Enhanced patient serum immunoreactivity to recombinant Mycobacterium tuberculosis
      CFP32 produced in the yeast Pichia pastoris compared to Escherichia coli and its
      potential for serodiagnosis of tuberculosis.
AB  - CFP32 is a Mycobacterium tuberculosis complex-restricted secreted protein that
      was previously reported to be present in a majority of sputum samples from
      patients with active tuberculosis (TB) and to stimulate serum antibody
      production. CFP32 (originally annotated as Rv0577 and also known as TB27.3) was
      therefore considered a good candidate target antigen for the rapid serodiagnosis
      of TB. However, the maximal sensitivity of CFP32 serorecognition may have been
      limited in earlier studies because recombinant CFP32 (rCFP32) produced in
      Escherichia coli was used as the test antibody-capture antigen, a potential
      shortcoming stemming from differences in bacterial protein posttranslational
      modifications. To further investigate the serodiagnostic potential of rCFP32
      synthesized in different heterologous hosts, we expressed rCFP32 in the yeast
      Pichia pastoris. Compared to E. coli rCFP32, yeast rCFP32 showed a higher
      capacity to capture polyclonal antisera in Western blot studies. Likewise, yeast
      rCFP32 was significantly better recognized by the sera from TB patients and
      healthy Mycobacterium bovis bacillus Calmette-Guerin (BCG)-vaccinated
      individuals, by enzyme-linked immunosorbent assay (ELISA), than E. coli rCFP32.
      In subsequent testing, the yeast rCFP32-based antibody-capture ELISA had a
      sensitivity of 85% and a specificity of 98% for the discrimination of active TB
      cases (n = 40) from BCG vaccinees (n = 39). The sensitivity was surprisingly high
      for a single-antigen TB serodiagnostic test compared to tests using E. coli
      expressed antigens. Overall, the trans-production of rCFP32 in P. pastoris
      significantly improved the serologic detection of CFP32-specific antibodies in
      patient sera, thereby offering a new, possibly better, modality for producing
      antigens of diagnostic potential for use in the development of immunoassays for
      both TB and other infectious diseases.

PMID- 16954232
TI  - Serological detection of varicella-zoster virus-specific immunoglobulin G by an
      enzyme-linked immunosorbent assay using glycoprotein antigen.
AB  - Since the introduction of varicella vaccination in several countries, there has
      been an urgent need for commercially available test procedures that allow highly
      sensitive and specific quantitative determination of the varicella-zoster virus
      (VZV)-specific immune status, including immunity postimmunization. This study
      compared the performance of two enzyme-linked immunosorbent assays (ELISAs) for
      the sensitive and specific determination of VZV-specific immunoglobulin G (IgG)
      in seronegative and latently infected persons, as well as in vaccinees. One ELISA
      is based on the detection of antibody to VZV-specific envelope glycoproteins
      (gp), and the other comprises the whole antigen extract prepared from VZV
      infected cells. A modified standard fluorescent-antibody-to-membrane-antigen
      (FAMA) assay was used as a reference. An excellent sensitivity (100%) in relation
      to FAMA was demonstrated for the gpELISA (Virion?Serion), while the non-gpELISA
      (Dade Behring) had a lower sensitivity (83%) when sera from latently infected
      persons were tested. After postvaccinal immunity was measured, a sensitivity of
      87% was achieved with gpELISA, whereas the ELISA incorporating antigen extract of
      VZV-infected cells had a sensitivity of 78%. Excellent specificity (100%) was
      calculated for both the gpELISA and the non-gpELISA. In conclusion, SERION ELISA
      classic VZV IgG is useful for the sensitive and specific quantitative
      determination of VZV immune status after natural infection. The test can also be
      recommended for measuring antibody response after varicella vaccination,
      particularly after the cutoff value was optimized.

PMID- 16954233
TI  - Multicenter evaluation of the Etest and disk diffusion methods for
      differentiating daptomycin-susceptible from non-daptomycin-susceptible
      Staphylococcus aureus isolates.
AB  - Daptomycin is a novel cyclic lipopeptide that is approved by the U.S. Food and
      Drug Administration for the treatment of complicated skin and skin structure
      infections associated with Staphylococcus aureus and other gram-positive
      pathogens and also staphylococcal bacteremia, including right-sided endocarditis.
      The Clinical and Laboratory Standards Institute (CLSI) established "susceptible
      only" interpretive criteria for broth microdilution (BMD) and disk diffusion (DD)
      testing of daptomycin in 2005. However, a series of S. aureus isolates have been
      recovered with daptomycin MICs in the nonsusceptible range (i.e., MICs of >1
      microg/ml). The objective of this study was to determine the ability of the Etest
      and DD methods to differentiate daptomycin-susceptible from nonsusceptible
      isolates of S. aureus compared to the results of the CLSI BMD reference method.
      There was a good correlation between Etest MIC results and the results of BMD
      among laboratories (r = 0.86 to 0.88), with 95.3% of the Etest MICs within a +/-1
      log(2) dilution of the BMD MIC result. A total of 92 of 102 (90.2%) non
      daptomycin-susceptible isolates of S. aureus identified by BMD in two
      participating laboratories were also classified as nonsusceptible by Etest.
      However, the very major and major error rates reported by one of the
      participating laboratories were 13.5 and 4.0%, respectively, primarily due to the
      absence of an intermediate category. The DD method, however, did not reliably
      differentiate daptomycin-susceptible from non-daptomycin-susceptible isolates. In
      2005, daptomycin disks were voluntarily removed from the market by Cubist
      Pharmaceuticals. The disk diffusion breakpoints were subsequently removed from
      the CLSI M100 standard in 2006.

PMID- 16954234
TI  - Effect of primer selection on estimates of GB virus C (GBV-C) prevalence and
      response to antiretroviral therapy for optimal testing for GBV-C viremia.
AB  - GB virus C (GBV-C; also called hepatitis G virus) is a common cause of infection
      associated with prolonged survival among HIV-infected individuals. The
      prevalences of GBV-C viremia vary widely in different studies, and there has been
      poor agreement among different laboratories performing GBV-C RNA detection in
      quality control studies. To determine the optimal method of measuring GBV-C RNA
      in clinical samples, samples obtained from 939 HIV-infected subjects were studied
      using reverse transcription (RT)-PCR methods amplifying four separate regions of
      the GBV-C genome. Primers amplifying the E2 coding region were 100% specific;
      however, their sensitivity was only 76.6%. In contrast, primers amplifying three
      additional conserved regions of the GBV-C genome (the 5' nontranslated region and
      the nonstructural protein-coding regions 3 and 5A) were more sensitive but
      produced higher rates of false-positive results. Using low-specificity primer
      sets influenced the significance of association between GBV-C viremia and
      response to antiretroviral therapy. Using a quantitative GBV-C RNA method, the
      GBV-C RNA concentration did not correlate with baseline or set point HIV RNA
      levels; however, a correlation between negative, low, and high GBV-C RNA levels
      and increasing reduction in HIV RNA following antiretroviral therapy was
      observed. Subjects with both GBV-C E2 antibody and viremia had significantly
      lower GBV-C RNA levels than did viremic subjects without E2 antibody. These
      studies demonstrate that accurate detection of GBV-C RNA by nested RT-PCR
      requires the use of primers representing multiple genome regions. Analyses based
      on testing with single primers do not lead to reliable conclusions about the
      association between GBV-C infection and clinical outcomes.

PMID- 16954235
TI  - Optimization and validation of recombinant serological tests for African Swine
      Fever diagnosis based on detection of the p30 protein produced in Trichoplusia ni
      larvae.
AB  - We describe the validation of an enzyme-linked immunosorbent assay (ELISA) and
      confirmatory immunoblotting assays based on a recombinant p30 protein (p30r)
      produced in insect larvae using a baculovirus vector. Such validation included
      the following: (i) the scaling up and standardization of p30r production and the
      associated immunoassays, (ii) a broad immunological analysis using a large number
      of samples (a total of 672) from Spain and different African locations, and (iii)
      the detection of the ASF virus (ASFV)-antibody responses at different times after
      experimental infection. Yields of p30r reached up to 15% of the total protein
      recovered from the infected larvae at 3 days postinfection. Serological analysis
      of samples collected in Spain revealed that the p30r-based ELISA presented
      similar sensitivity to and higher specificity than the conventional Office
      International des Epizooties-approved ASFV ELISA. Moreover, the p30r ELISA was
      more sensitive than the conventional ELISA test in detecting ASFV-specific
      antibodies in experimentally infected animals at early times postinfection. Both
      the recombinant and conventional ELISAs presented variable rates of sensitivity
      and specificity with African samples, apparently related to their geographical
      origin. Comparative analyses performed on the sequences, predicted structures,
      and antigenicities of p30 proteins from different Spanish and African isolates
      suggested that variability among isolates might correlate with changes in
      antigenicity, thus affecting detection by the p30r ELISA. Our estimations
      indicate that more than 40,000 ELISA determinations and 2,000 confirmatory
      immunoblotting tests can be performed with the p30r protein obtained from a
      single infected larva, making this a feasible and inexpensive strategy for
      production of serological tests with application in developing countries.

PMID- 16954236
TI  - Evaluation of the SPF10-INNO LiPA human papillomavirus (HPV) genotyping test and
      the roche linear array HPV genotyping test.
AB  - The need for accurate genotyping of human papillomavirus (HPV) infections is
      becoming increasingly important, since (i) the oncogenic potential among the high
      risk HPV genotypes varies in the pathogenesis of cervical cancer, (ii) monitoring
      multivalent HPV vaccines is essential to investigate the efficiency of the
      vaccines, and (iii) genotyping is crucial in epidemiologic studies evaluating HPV
      infections worldwide. Various genotyping assays have been developed to meet this
      demand. Comparison of different studies that use various HPV genotyping tests is
      possible only after a performance assessment of the different assays. In the
      present study, the SPF(10) LiPA version 1 and the recently launched Roche Linear
      Array HPV genotyping assays are compared. A total of 573 liquid-based cytology
      samples were tested for the presence of HPV by a DNA enzyme immunoassay; 210 were
      found to be positive for HPV DNA and were evaluated using both genotyping assays
      (163 with normal cytology, 22 with atypical squamous cells of undetermined
      significance, 20 with mild/moderate dysplasia, and 5 with severe dysplasia).
      Comparison analysis was limited to the HPV genotype probes common to both assays.
      Of the 160 samples used for comparison analysis, 129 (80.6%) showed absolute
      agreement between the assays (concordant), 18 (11.2%) showed correspondence for
      some but not all genotypes detected on both strips (compatible), and the
      remaining 13 (8.2%) samples did not show any similarity between the tests
      (discordant). The overall intertest comparison agreement for all individually
      detectable genotypes was considered very good (kappa value, 0.79). The genotyping
      assays were therefore highly comparable and reproducible.

PMID- 16954237
TI  - Quantitative assessment of serum NV-F virus DNA concentrations in samples from
      patients coinfected with hepatitis B or C virus.
AB  - A novel hepatotropic virus, named NV-F virus, was recently identified. The
      clinical information for this virus is still scarce. Using PCR assay, NV-F viral
      DNA (NV-F-DNA) was detected in 12 of 50 (24%) hepatitis C virus (HCV)-infected
      patients (HCV-coinfected [HCVCI] group), 34 of 250 (13.6%) hepatitis B virus
      (HBV)-infected patients (HBV-coinfected [HBVCI] group), and 28 of 100 (28%) non-A
      to-E (NAE) hepatitis patients. Basic clinical parameters were not significantly
      different among the three groups. By use of a PCR-based quantitative assay, the
      NV-F-DNA concentration was found to be above the detection limit (1.2 x 10(5)
      copies/ml) in 12/12 (100%) HCVCI patients, 14/34 (41.2%) HBVCI patients, and 4/28
      (14.3%) NAE patients. The median serum NV-F-DNA concentration was 9.3 x 10(5)
      copies/ml in HCVCI patients, but it was below the detection limit in HBVCI and
      NAE patients (P values were 0.0045 and 0.0001, respectively). Stepwise multiple
      regression analysis identified the presence of anti-HCV as an independent factor
      for NV-F-DNA concentrations (beta = 6.2 x 10(9); P = 0.0245). In HBVCI patients,
      the NV-F-DNA concentration was inversely correlated with the HBV DNA
      concentration. The median NV-F-DNA concentration was below the detection limit in
      patients with HBV DNA concentrations above 1.4 x 10(5) copies/ml, but it was 1.58
      x 10(6) copies/ml in patients with HBV DNA concentrations below 1.4 x 10(5)
      copies/ml (P = 0.030). In conclusion, NV-F-DNA concentrations were higher in
      HCVCI patients. A reciprocal relationship was found between NV-F-DNA and HBV DNA
      concentrations in HBVCI patients, indicating the presence of viral interference
      between these two DNA viruses.

PMID- 16954238
TI  - Serodiagnosis using recombinant nipah virus nucleocapsid protein expressed in
      Escherichia coli.
AB  - Nipah virus nucleocapsid (NiV-N) protein was expressed in Escherichia coli and
      purified by histidine tag-based affinity chromatography. An indirect
      immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) for human and
      swine sera and an IgM capture ELISA for human sera were established using the
      recombinant NiV-N protein as an antigen. One hundred thirty-three suspected
      patient sera and 16 swine sera were used to evaluate the newly established ELISA
      systems in comparison with the CDC inactivated-virus-based ELISA systems. For the
      human sera, the NiV-N protein-based indirect IgG ELISA had a sensitivity of 98.6%
      and a specificity of 98.4%, and the NiV-N protein-based IgM capture ELISA had a
      sensitivity of 91.7% and a specificity of 91.8%, with reference to the CDC ELISA
      systems. The NiV-N-based IgM ELISA was found to be more sensitive than the
      inactivated-virus-based ELISA in that it captured eight additional cases. For the
      swine sera, the two test systems were in 100% concordance. Our data indicate that
      the Nipah virus nucleocapsid protein is a highly immunogenic protein in human and
      swine infections and a good target for serodiagnosis. Our NiV-N protein-based
      ELISA systems are useful, safe, and affordable tools for diagnosis of Nipah virus
      infection and are especially fit to be used in large-scale epidemiological
      investigations and to be applied in developing countries.

PMID- 16954239
TI  - Phenotypic detection of carbapenem-susceptible metallo-beta-lactamase-producing
      gram-negative bacilli in the clinical laboratory.
AB  - Rapid detection of metallo-beta-lactamase (MBL)-producing gram-negative pathogens
      is critical to prevent their widespread dissemination. Thus far, no standardized
      phenotypic method is available, and previously reported techniques have poor
      sensitivity for detecting carbapenem-susceptible MBL-carrying isolates, an
      increasingly described phenomenon. We developed a phenotypic detection method
      using both a double-disk synergy test and a combined-disk test with imipenem and
      292 microg EDTA on one agar plate. Genotypic confirmation was used for
      validation. Of the 134 clinical isolates, 84 were confirmed to carry an MBL. Of
      these, 51 (61%) were susceptible to at least one carbapenem, and 22 (26%) were
      isolated from blood. The phenotypic method correctly differentiated all MBL
      producing isolates (sensitivity, 100%). Fifty-one of the 52 MBL-negative isolates
      were correctly differentiated (specificity, 98%). This study reports the
      validation of a simple and accurate MBL detection method that can be easily
      incorporated into the daily routine of a clinical laboratory. Early detection of
      MBL-carrying organisms, including those with susceptibility to carbapenems, is of
      paramount clinical importance, as it allows rapid initiation of strict infection
      control practices as well as therapeutic guidance for confirmed infection.

PMID- 16954240
TI  - Nucleotide sequence-based analysis for determining the molecular epidemiology of
      Penicillium marneffei.
AB  - The dimorphic fungus, Penicillium marneffei, is an emerging opportunistic
      pathogen endemic in Southeast Asia, especially for those with impaired cellular
      immunity such as human immunodeficiency virus-infected persons. A discriminatory
      and reproducible method based on the analysis of nucleotide sequences would
      facilitate epidemiologic investigations of this fungus. Twenty-four clinical or
      environmental isolates of P. marneffei obtained from China, Thailand, and Vietnam
      were analyzed by nucleotide sequence analysis. A total of 3,803 bp, consisting of
      eight nuclear gene fragments (transcription factor [AbaA], catalase [CpeA]],
      homodomain transcription factor [StlA], isocitrate lyase [Icl1], polyaromatic
      amino acid biosynthesis [PAA], NADH-dependent glutamate synthase [NGS],
      lovastatin nonaketide synthase [LNS], a cell wall mannoprotein [MP1], and a gene
      fragment of the cytochrome oxidase subunit 1 gene [COX1] of the P. marneffei
      mitochondrial genome) were amplified by PCR and then sequenced. No polymorphic
      sites within the Cox1 gene fragment were observed. Likewise, no nucleotide
      sequence polymorphisms were observed for three gene fragments: StlA, AbaA, and
      NGS. Seven single-nucleotide polymorphisms were observed for three gene
      fragments, Icl1, CpeA, and PAA, providing only a low degree of discriminatory
      power (D = 0.747). In contrast, the gene fragment for an antigenic cell wall
      glycoprotein, MP1, a useful immunologic marker for infection, was observed to be
      highly polymorphic with 12 different MP1 types (D = 0.887). Single-nucleotide
      polymorphisms were observed at 21 different locations in the MP1 gene fragment.
      Indels of 3, 21, 24, and 42 bp were observed and were in frame for protein
      translation. The relatively high degree of MP1 polymorphisms suggests the
      sequence is rapidly evolving in order to evade host immune responses. After all
      polymorphic gene sequences were combined, a high degree of genetic variation was
      observed (D = 0.949) for a total of 16 different haploid sequence types with 11
      genotypes represented by single isolates. Phylogenetic analysis detected clusters
      composed of isolates obtained only from China or Thailand, as well as clusters
      with a combination of isolates from these two countries, indicating some mixing
      or common descent. Identical sequences were observed for isolates passed in vitro
      for 8 weeks, suggesting good reproducibility. The low degree of nucleotide
      diversity in housekeeping and regulatory genes suggests the recent emergence and
      spread as a species or an evolutionary bottleneck. In summary, multilocus
      sequence typing demonstrated a high degree of discriminatory power and
      reproducibility and may provide a robust and reliable adjunct method for
      genotyping isolates of P. marneffei and facilitating interlaboratory comparisons.

PMID- 16954241
TI  - Evaluation of real-time and conventional PCR targeting complex 85 genes for
      detection of Mycobacterium leprae DNA in skin biopsy samples from patients
      diagnosed with leprosy.
AB  - In spite of the decrease in the number of registered leprosy patients, the number
      of new cases diagnosed each year (400,000) has remained essentially unchanged.
      Leprosy diagnosis is difficult due to the low sensitivity of current
      methodologies to identify new cases. In this study, conventional and TaqMan real
      time PCR assays for detection of Mycobacterium leprae DNA were compared to
      current classification based on clinical, bacteriological, and histological
      evaluation. M. leprae DNA was extracted from frozen skin biopsy specimens from 69
      leprosy patients enrolled in the study and was amplified using specific primers
      for either the antigen 85B-coding gene or the 85A-C intergenic region by using
      conventional and real-time PCR. The detection rate was 100% among multibacillary
      (MB) patients and ranged from 62.5% to 79.2% among paucibacillary (PB) patients
      according to the assay used. The TaqMan system for 85B gene amplification showed
      the highest sensitivity, although conventional PCR using the 85A-C gene as a
      target was also efficient. The cycle threshold (C(T)) values obtained using the
      TaqMan system were able to statistically (P < 0.0001) differentiate MB (mean
      C(T), 28.06; standard deviation [SD], 4.51) from PB (mean C(T), 33.06; SD, 2.24)
      patients. Also, there was a correlation between C(T) values and the
      bacteriological index for MB patients (Pearson's r, -0.444; P = 0.008). Within
      the PB patients' group, we tested normal skin from six patients exhibiting the
      pure neuritic form of leprosy (PNL). Five out of six PNL patients were positive
      for the presence of M. leprae DNA, even in the absence of skin lesions. In
      conclusion, the TaqMan real-time PCR developed here seems to be a useful tool for
      rapidly detecting and quantifying M. leprae DNA in clinical specimens in which
      bacilli were undetectable by conventional histological staining.

PMID- 16954242
TI  - Comparative evaluation of early diagnosis of tuberculous meningitis by different
      assays.
AB  - Cerebrospinal fluid (CSF) and peripheral blood (PBL) were sampled multiple times
      from 25 patients with a clinical diagnosis of tuberculous meningitis (TBM) and 49
      controls, including 27 patients with other infectious diseases of the central
      nervous system and 22 patients with other noninfectious neurological diseases. We
      used an enzyme-linked immunospot assay (ELISPOT) to detect anti-Mycobacterium
      bovis BCG antibody-secreting cells in CSF and PBL, PCR to detect a repeated
      insertion sequence (IS6110) specific for Mycobacterium tuberculosis in CSF, and
      an enzyme-linked immunosorbent assay (ELISA) to detect anti-BCG antibodies in CSF
      and PBL. In the meantime, culture of CSF from every TBM and control patient was
      done on Lowenstein-Jensen medium. ELISPOT proved to be the most valuable test,
      with a sensitivity of 84.0% and a specificity of 91.8%, and showed a sensitivity
      of 100.0% with the CSF specimens obtained within 4 weeks after the onset of TBM.
      The numbers of CSF anti-BCG immunoglobulin-secreting cells tested by ELISPOT were
      even higher in the early phase of TBM and declined while the disease was going on
      (P = 0.008), which allowed an early diagnosis to be made. The sensitivities of
      PCR and ELISA were only 75.0% and 52.3%, respectively; and the specificities were
      93.7% and 91.6%, respectively. Culture of CSF on Lowenstein-Jensen medium was the
      least sensitive (16%) compared to the sensitivities of the other three assays.
      Our results demonstrate that the ELISPOT technique is worthy for routine use in
      the laboratory to support the clinical diagnosis of TBM.

PMID- 16954243
TI  - Rapid identification of ascomycetous yeasts from clinical specimens by a
      molecular method based on flow cytometry and comparison with identifications from
      phenotypic assays.
AB  - This study was designed to compare the identification of ascomycetous yeasts
      recovered from clinical specimens by using phenotypic assays (PA) and a molecular
      flow cytometric (FC) method. Large-subunit rRNA domains 1 and 2 (D1/D2) gene
      sequence analysis was also performed and served as the reference for correct
      strain identification. A panel of 88 clinical isolates was tested that included
      representatives of nine commonly encountered species and six infrequently
      encountered species. The PA included germ tube production, fermentation of seven
      carbohydrates, morphology on corn meal agar, urease and phenoloxidase activities,
      and carbohydrate assimilation tests when needed. The FC method (Luminex) employed
      species-specific oligonucleotides attached to polystyrene beads, which were
      hybridized with D1/D2 amplicons from the unidentified isolates. The PA identified
      81 of 88 strains correctly but misidentified 4 of Candida dubliniensis, 1 of C.
      bovina, 1 of C. palmioleophila, and 1 of C. bracarensis. The FC method correctly
      identified 79 of 88 strains and did not misidentify any isolate but did not
      identify nine isolates because oligonucleotide probes were not available in the
      current library. The FC assay takes approximately 5 h, whereas the PA takes from
      2 h to 5 days for identification. In conclusion, PA did well with the commonly
      encountered species, was not accurate for uncommon species, and takes
      significantly longer than the FC method. These data strongly support the
      potential of FC technology for rapid and accurate identification of medically
      important yeasts. With the introduction of new antifungals, rapid, accurate
      identification of pathogenic yeasts is more important than ever for guiding
      antifungal chemotherapy.

PMID- 16954244
TI  - Temperature gradient gel electrophoresis of fecal 16S rRNA reveals active
      Escherichia coli in the microbiota of patients with ulcerative colitis.
AB  - Previous studies of the endogenous microbiota in patients with ulcerative colitis
      (UC) have not taken bacterial activity into account, yet bacteria with high
      transcriptional activity might have a more important pathophysiological role than
      inactive bacteria. We therefore analyzed the biodiversity of active bacteria in
      the fecal microbiota of UC patients, in comparison with that of healthy subjects.
      Feces were collected from nine patients with active UC and from nine healthy
      controls. Total DNA and RNA were extracted, and 16S ribosomal DNA and RNA were
      amplified by PCR and reverse transcription-PCR, respectively. Amplification
      products were compared by means of temporal temperature gradient gel
      electrophoresis (TTGE). Bands of interest were excised, sequenced, and identified
      by comparison with the GenBank database (NCBI). The dominant-species diversity
      based on RNA-derived TTGE profiles was significantly lower for UC patients than
      for healthy controls (P = 0.01). The mean similarity index between the "present"
      and "active" microbiota was 74% +/- 18% for UC patients. Comparison of the
      individual "active" microbiota identified a band that was present for eight UC
      patients and only two controls (89% versus 22%; P = 0.008). The band was
      sequenced for 6 patients and always corresponded to Escherichia coli. The
      biodiversity of active bacteria in the dominant fecal microbiota of patients with
      UC is lower than that of healthy subjects. E. coli is more represented in the
      active microbiota of UC patients. The possible pathophysiological role of this
      difference remains to be determined.

PMID- 16954245
TI  - Detection and characterization of bovine coronaviruses in fecal specimens of
      adult cattle with diarrhea during the warmer seasons.
AB  - Bovine coronavirus (BCoV) is an etiological agent associated with winter
      dysentery (WD), prevalent in adult cattle during the winter. Although we
      previously detected, isolated, and characterized BCoV strains from adult cattle
      with WD (WD-BCoV strains) during the winter in South Korea, the precise
      epidemiology, as well as the causative agent of diarrhea in adult cattle in the
      warmer seasons, has not been examined. We examined 184 diarrheic fecal specimens
      collected from 75 herds of adult cattle from seven provinces during the spring
      (warm), autumn (warm), and summer (hot) seasons. Bovine coronavirus-positive
      reactions were detected for 107 (58.2%) diarrheic fecal samples (in 47/75 herds).
      Of these 107 positive samples, 90 fecal samples from 33 herds tested positive for
      BCoV alone and 17 fecal samples from 14 herds also tested positive for other
      pathogens. Biological comparisons between the 9 BCoV strains isolated in this
      study and the 10 previously isolated WD-BCoV strains revealed that there was no
      receptor-destroying enzyme (RDE) activity against mouse erythrocytes in the 9
      BCoV strains but the 10 WD-BCoV strains had high RDE activity. Phylogenetic
      analysis of the spike (S) and hemagglutinin/esterase (HE) proteins revealed that
      all the Korean BCoVs clustered together regardless of season and were distinct
      from the other known BCoVs, suggesting a distinct evolutionary pathway for the
      Korean BCoVs. These and previous results revealed a high prevalence and
      widespread geographical distribution of BCoV, suggesting that this virus is
      endemic in adult cattle with diarrhea in all seasons in South Korea.

PMID- 16954246
TI  - Real-time reverse transcription-PCR for detection of rotavirus and adenovirus as
      causative agents of acute viral gastroenteritis in children.
AB  - Viral pathogens are the most common cause of gastroenteritis in developed
      countries. Human rotavirus and adenovirus infections are major causes of acute
      outbreaks and sporadic cases of gastroenteritis, occurring primarily among
      children less than 2 years of age. Patient hospitalization is often required,
      with enormous infection control implications. This work describes the development
      of real-time PCR assays for the detection of group F adenovirus, rotavirus A, and
      rotavirus C from stool specimens. Two hundred twenty stool samples from pediatric
      patients exhibiting symptoms of diarrhea and/or vomiting were examined. PCR
      results were compared with those of virus detection by electron microscopy and
      latex agglutination antigen detection. The incorporation of an internal-control
      RNA that was spiked into individual stool extracts functioned as an internal
      validation for the reporting of PCR-negative results. Rotavirus C was not
      detected by real-time PCR in the patient stool samples examined. Real-time
      reverse transcription-PCR resulted in 175% and 111% increases in the rates of
      detection of adenovirus F and rotavirus A, respectively, compared with latex
      agglutination testing. Molecular detection increased the number of stool
      specimens in which causative agents of gastroenteritis were identified by 155%
      compared to electron microscopy. Genotyping of a proportion of the rotavirus and
      adenovirus strains identified only genotype G1 rotavirus and both adenovirus
      genotypes 40 and 41 in circulation within the patient cohort examined. The
      results highlight the significance of rapid molecular methods for the routine
      screening of stool samples in hospital laboratories to provide rapid definitive
      diagnoses.

PMID- 16954247
TI  - Differential detection of Entamoeba histolytica, Entamoeba dispar, and Entamoeba
      moshkovskii by a single-round PCR assay.
AB  - A single-round PCR assay was developed for detection and differential diagnosis
      of the three Entamoeba species found in humans, Entamoeba moshkovskii, Entamoeba
      histolytica, and Entamoeba dispar, that are morphologically identical as both
      cysts and trophozoites. A conserved forward primer was derived from the middle of
      the small-subunit rRNA gene, and reverse primers were designed from signature
      sequences specific to each of these three Entamoeba species. PCR generates a 166
      bp product with E. histolytica DNA, a 752-bp product with E. dispar DNA, and a
      580-bp product with E. moshkovskii DNA. Thirty clinical specimens were examined,
      and the species present were successfully detected and differentiated using this
      assay. It was possible to detect as little as 10 pg of E. moshkovskii and E.
      histolytica DNA, while for E. dispar the sensitivity was about 20 pg of DNA.
      Testing with DNA from different pathogens, including bacteria and other protozoa,
      confirmed the high specificity of the assay. We propose the use of this PCR assay
      as an accurate, rapid, and effective diagnostic method for the detection and
      discrimination of these three morphologically indistinguishable Entamoeba species
      in both routine diagnosis of amoebiasis and epidemiological surveys.

PMID- 16954248
TI  - An outbreak of keratitis caused by Mycobacterium immunogenum.
AB  - From 8 October to 12 November 2003, 36 patients underwent surgical correction of
      myopia in a Sao Paulo, Brazil, clinic. Five patients had clinical signs of
      infectious keratitis, and a Mycobacterium species with previously unreported
      patterns determined by PCR restriction enzyme analysis of the hsp65 gene and PCR
      restriction enzyme analysis of the 16S-23S rRNA internal transcribed spacer (ITS)
      was isolated from corneal scrapings from four of these patients. Subsequent
      evaluation by phenotypic tests and partial sequencing of the hsp65, sodA, rpoB,
      and 16S rRNA genes and the ITS supported the species identification as a variant
      of Mycobacterium immunogenum. The source of infection was not determined. The
      outbreak was caused by a single clone, as evidenced by identical pulsed-field gel
      electrophoresis and enterobacterial repetitive intergenic consensus-PCR profiles.
      This is the first report of an outbreak where this species was isolated from
      infected tissues.

PMID- 16954249
TI  - The key role of pulsed-field gel electrophoresis in investigation of a large
      multiserotype and multistate food-borne outbreak of Salmonella infections
      centered in Pennsylvania.
AB  - Five different serotypes of Salmonella enterica were implicated in a large
      outbreak linked to fresh Roma tomatoes served at gas station deli counters in
      Pennsylvania and nearby states during July 2004: S. enterica serotypes Javiana,
      Anatum, Thompson, Typhimurium, and Muenchen. One of these serotypes, Anatum, was
      isolated from both tomatoes and patients. Pulsed-field gel electrophoresis (PFGE)
      played a key role in identifying the outbreak-associated isolates and
      distinguishing them from unrelated sporadic isolates. It also demonstrated that
      the genetic fingerprints of serotype Anatum isolates derived from patients were
      indistinguishable from those derived from tomatoes. Rapid communication of PFGE
      fingerprints with other public health laboratories through the Centers for
      Disease Control and Prevention's PulseNet USA national molecular surveillance
      network for bacterial food-borne pathogens facilitated the tracking of this
      outbreak in other states. The work described in this report emphasizes the
      laboratory's role in core public health functions and services, thereby providing
      a highly visible example of public health in action.

PMID- 16954250
TI  - Genital Candida species detected in samples from women in Melbourne, Australia,
      before and after treatment with antibiotics.
AB  - Vulvovaginal candidiasis (VVC) remains a common cause of morbidity, with three
      quarters of women affected during their lifetimes. Use of antibiotics is an
      acknowledged trigger for VVC, which adversely affects women's physical and
      emotional health. Knowledge of patterns of genital Candida species-level
      identification is important for management, as Candida species other than Candida
      albicans often fail first-line treatment. A community sample of women with no
      vaginal symptoms, and who were prescribed antibiotics, was recruited into this
      study, where the incidence of genital colonization by various Candida species was
      documented, as well as symptoms of VVC plus relevant associations, before and
      after treatment with antibiotics. Self-collected low vaginal swabs were taken
      prior to and 8 days after completion of antibiotic treatment, and data on various
      potential risk factors for VVC were collected simultaneously, with complete data
      being available for 233 participants. Baseline Candida species colonization was
      present in 21% of women (95% confidence intervals [CI], 17% to 27%), rising to
      37% (95% CI, 31% to 44%) after antibiotic treatment. The primary species detected
      for either period was C. albicans (73%), with Candida glabrata detected in around
      20%. Self-assessed proneness to VVC after antibiotic treatment and baseline
      colonization with Candida spp. were significantly associated with symptomatic VVC
      after antibiotic treatment. For microbiologically proven candidiasis, VVC
      symptoms had a sensitivity of 57% and a specificity of 91%. When physicians
      prescribe antibiotics, the history of risk of VVC is one issue that physicians
      should discuss with women, particularly those who are self-identified as being
      prone to VVC. Furthermore, we recommend that definitive microbiological diagnoses
      be made for women with recurrent symptoms or those failing initial treatment, to
      guide appropriate therapy.

PMID- 16954251
TI  - Molecular epidemiology of rabies virus isolates in India.
AB  - In India, rabies is enzootic and is a serious public health and economic problem.
      India has a large population of stray dogs which, together with a lack of
      effective control strategies, might have led to the persistence of rabies virus
      (RV) in the canine population. Our objective was to study the molecular
      epidemiology of RV isolates in India based on nucleotide sequence analysis of 29
      RV isolates originating from different species of animals in four states. Here we
      have analyzed two sets of sequence data based upon a 132-nucleotide region of the
      cytoplasmic domain (CD) of the G gene (G-CD) and a 549-nucleotide region (Psi-L)
      that combines the noncoding G-L intergenic region (Psi) and a fragment of the
      polymerase gene (L). Phylogenetic analysis revealed that the RV isolates belong
      to genotype 1 and that they were related geographically but were not related
      according to host species. Five different genetic clusters distributed among
      three geographical regions were identified. Comparison of the deduced amino acid
      sequences of G-CD between RV isolates revealed three amino acid changes (amino
      acid 462G [aa462G], aa465H, and aa468K) that distinguished the Indian RVs from RV
      isolates in other parts of the world. Analysis of the data indicated that the dog
      rabies virus variants are the major circulating viruses in India that transmit
      the disease to other domestic animals and humans as well.

PMID- 16954252
TI  - Molecular characterization of non-penicillin-susceptible Streptococcus pneumoniae
      in Norway.
AB  - A total of 125 non-penicillin-susceptible Streptococcus pneumoniae isolates were
      received at the Norwegian Institute of Public Health in the period from 1995 to
      2001. The strains were tested for antimicrobial susceptibility, serotyped, and
      genotyped by multilocus sequence typing (MLST); and their penicillin-binding
      proteins (PBPs) were typed by restriction fragment length polymorphism analysis
      of their pbp genes. Of the 125 strains, 48 (38%) were fully resistant to
      penicillin and 77 (62%) were intermediately resistant to penicillin. Most of the
      strains resistant to penicillin were also resistant to one or several additional
      antibiotics. The most frequent serotypes among the non-penicillin-susceptible
      strains were 14, 9V, 19F, 23F, and 6B. MLST analysis showed a high degree of
      genetic diversity among the 119 strains tested, with a total of 74 different
      sequence types. Six of the 26 internationally known resistant clones were
      present; the Spain(9V)-3 clone was the most frequent, with 19 isolates. A total
      of 74 (62%) of the isolates were related to 1 of the 26 international clones.
      Restriction enzyme analyses of the pbp1a, pbp2b, and pbp2x genes revealed 12, 12,
      and 19 different patterns, respectively; and a total of 43 different PBPs types
      were demonstrated. Our data indicate that the non-penicillin-susceptible strains
      in Norway are highly diverse genetically and that limited spread of the
      internationally known resistant strains occurred in the country in the period
      examined.

PMID- 16954253
TI  - Real-time PCR assays for detection of bocavirus in human specimens.
AB  - The recently discovered human bocavirus (HBoV) is the first member of the family
      Parvoviridae, genus Bocavirus, to be potentially associated with human disease.
      Several studies have identified HBoV in respiratory specimens from children with
      acute respiratory disease, but the full spectrum of clinical disease and the
      epidemiology of HBoV infection remain unclear. The availability of rapid and
      reliable molecular diagnostics would therefore aid future studies of this novel
      virus. To address this, we developed two sensitive and specific real-time TaqMan
      PCR assays that target the HBoV NS1 and NP-1 genes. Both assays could
      reproducibly detect 10 copies of a recombinant DNA plasmid containing a partial
      region of the HBoV genome, with a dynamic range of 8 log units (10(1) to 10(8)
      copies). Eight blinded clinical specimen extracts positive for HBoV by an
      independent PCR assay were positive by both real-time assays. Among 1,178 NP
      swabs collected from hospitalized pneumonia patients in Sa Kaeo Province,
      Thailand, 53 (4.5%) were reproducibly positive for HBoV by one or both targets.
      Our data confirm the possible association of HBoV infection with pneumonia and
      demonstrate the utility of these real-time PCR assays for HBoV detection.

PMID- 16954254
TI  - External quality assessment of molecular typing of Staphylococcus aureus isolates
      by a network of laboratories.
AB  - A network of laboratories designated Centres for Molecular Diagnosis was funded
      in 2000 by Belgian National Health Insurance to provide clinically relevant
      molecular diagnostic tests. These included typing of nosocomial pathogens as a
      service to local hospital infection control programs. Two external quality
      assessment (EQA) surveys were performed in 2001 and 2003 to evaluate the
      proficiencies of the laboratories at Staphylococcus aureus typing. EQA panels
      included S. aureus isolates with either indistinguishable, clonally related, or
      unrelated pulsed-field gel electrophoresis (PFGE) patterns. A hypothetical
      hospital outbreak problem was also submitted for analysis. Typeability,
      reproducibility, discrimination (D) index, and epidemiological concordance were
      evaluated. Ten centers participated in each survey. Seven centers performed PFGE
      analysis, while others used repetitive-element or randomly amplified polymorphic
      DNA PCR, amplified fragment length polymorphism, or spa typing. Full typeability
      (100%) was achieved by all centers, and all but one showed 100% reproducibility.
      Discrimination was appropriate (D index, >or=96%) for centers performing PFGE
      analysis but not for all those using other methods (D index range, 72% to 97%).
      Correct answers to the epidemiological questions were provided by 7/10 and 10/10
      centers in 2001 and 2003, respectively. Individual feedback of results was
      provided to each center together with specific technical recommendations for
      improving performance. Our findings indicate that surveys of lab proficiency are
      useful for validation and optimization of molecular typing services to local
      hospital infection control programs.

PMID- 16954255
TI  - Loss of catabolic function in Streptococcus agalactiae strains and its
      association with neonatal meningitis.
AB  - The abilities of 151 Streptococcus agalactiae strains to oxidize 95 carbon
      sources were studied using the Biolog system. Two populations were constituted:
      one with a high risk of causing meningitis (HR group; 63 strains), and the other
      with a lower risk of causing meningitis (LR group; 46 strains). Strains belonging
      to the HR group were significantly less able to use four carbon sources, i.e.,
      alpha-D-glucose-1-phosphate, D-ribose, beta-methyl-D-glucoside, and D,L-alpha
      glycerol phosphate, than strains from the LR group (P <or= 0.004). Moreover,
      strains in the HR group significantly more frequently possessed one of several
      mobile genetic elements or genome deletions previously shown to be associated
      with strains responsible for neonatal meningitis than strains in the LR group (P
      < 0.001). These findings suggest that genetic disruption might have occurred in
      virulent clones of S. agalactiae. Fifteen biotypes (B1 to B15) were identified
      from the results of oxidation of the four carbon sources, of which six (B1 to B6)
      included 92% of the isolates belonging to the HR group. Strains of biotypes B1 to
      B6 are thus 13 times more likely to be able to invade the central nervous system
      of neonates than strains of biotypes B7 to B15. In addition, 86% of strains
      recently associated with neonatal meningitis (42 strains studied) were identified
      as being of biotypes B1 to B6. Identification of particular S. agalactiae
      biotypes may therefore be one of the criteria to assist clinicians in assessing
      the level of risk of neonatal meningitis when a mother and/or her neonate is
      colonized with S. agalactiae.

PMID- 16954256
TI  - Molecular phylogeny of Sporothrix schenckii.
AB  - The pathogenic dimorphic fungus Sporothrix schenckii is the agent responsible for
      sporotrichosis, an important fungal infection with a worldwide distribution.
      Little is known about the population structure of S. schenckii, although recent
      molecular and phenotypic data seem to demonstrate that different genetic lineages
      exist within this species. The aim of this study was to determine, by sequence
      analysis of three protein coding loci (chitin synthase, beta-tubulin, and
      calmodulin), whether this variability is due to species divergence or
      intraspecific diversity in S. schenckii. We included in the analysis 60 isolates
      (59 of clinical and 1 of environmental origin) of this species from a wide
      geographical range. DNA sequence data from the three nuclear regions were used in
      a phylogenetic analysis. The combined analysis of the three loci revealed the
      presence of three major clades, one grouping all of the European isolates,
      another with only Brazilian isolates, and the third with isolates from other
      South American countries and Africa. A total of 14 100% bootstrap-supported nodes
      were shown, 6 of them representing putative phylogenetic species. Our data also
      demonstrated that most of these species prevail in different geographical
      regions.

PMID- 16954257
TI  - Evaluation of the new VITEK 2 extended-spectrum beta-lactamase (ESBL) test for
      rapid detection of ESBL production in Enterobacteriaceae isolates.
AB  - Extended-spectrum beta-lactamases (ESBLs) are a large, rapidly evolving group of
      enzymes that confer resistance to oxyimino cephalosporins and monobactams and are
      inhibited by clavulanate. Rapid reliable detection of ESBL production is a
      prerequisite for successful infection management and for monitoring resistance
      trends and implementation of intervention strategies. We evaluated the
      performance of the new VITEK 2 ESBL test system (bioMerieux, Inc, Hazelwood, Mo.)
      in the identification of ESBL-producing Enterobacteriaceae isolates. We examined
      a total of 1,129 clinically relevant Enterobacteriaceae isolates (including 218
      that had been previously characterized). The ESBL classification furnished by the
      VITEK 2 ESBL test system was concordant with that of the comparison method
      (molecular identification of beta-lactamase genes) for 1,121 (99.3%) of the 1,129
      isolates evaluated. ESBL production was correctly detected in 306 of the 312 ESBL
      producing organisms (sensitivity, 98.1%; positive predictive value, 99.3%). False
      positive results emerged for 2 of the 817 ESBL-negative isolates (specificity,
      99.7%; negative predictive value, 99.3%). VITEK 2 ESBL testing took 6 to 13 h
      (median, 7.5 h; mean +/- SD, 8.2 +/- 2.39 h). This automated short-incubation
      system appears to be a rapid and reliable tool for routine identification of ESBL
      producing isolates of Enterobacteriaceae.

PMID- 16954258
TI  - Use of the Phoenix automated system for identification of Streptococcus and
      Enterococcus spp.
AB  - The Phoenix system (Becton Dickinson Diagnostic Systems, Sparks, MD) was
      evaluated for identification (ID) to the species level of streptococci and
      enterococci. Two hundred clinical isolates were investigated: beta-hemolytic
      streptococci (n = 50), Streptococcus pneumoniae organisms (n = 46), viridans
      group streptococci (n = 31), Enterococcus faecium (n = 36), Enterococcus faecalis
      (n = 25), and other catalase-negative cocci (n = 12). The API system (bioMerieux,
      Marcy l'Etoile, France) was used as a comparator. Molecular methods (sequencing
      of 16S rRNA and zwf and gki genes and ddl gene amplification) were used to
      investigate discordant results. Upon resolution of discrepancies, correct species
      ID was achieved by the Phoenix system for 121/129 (93.8%) streptococci and 63/70
      (90.0%) enterococci. Excellent results were obtained for S. pneumoniae (45/45)
      and beta-hemolytic streptococci (49/50). With regard to viridans streptococci,
      the accuracy of the Phoenix system was 83.9%. Among the latter organisms, the
      best performance was obtained with isolates of the Streptococcus sanguinis group
      and Streptococcus anginosus group; problems were instead encountered with the
      Streptococcus mitis group. Four E. faecium and three E. faecalis isolates were
      misidentified as Enterococcus casseliflavus/Enterococcus gallinarum or
      Enterococcus durans. Thus, these isolates were identified only at the genus
      level. Compared with commercially available systems, the Phoenix system appears a
      reliable diagnostic tool for identifying clinically relevant streptococci and
      enterococci. The SMIC/ID-2 panel proved particularly effective for beta-hemolytic
      streptococci and pneumococci.

PMID- 16954259
TI  - Development of a new method for diagnosis of rubella virus infection by reverse
      transcription-loop-mediated isothermal amplification.
AB  - We developed a useful method for the detection of rubella virus genome RNA by
      reverse transcription loop-mediated isothermal amplification (RT-LAMP) and
      compared the sensitivity of RT-LAMP with that of other virological tests: reverse
      transcription-PCR (RT-PCR) and virus isolation. The rubella virus genome was
      amplified by RT-LAMP from clinical isolates obtained between 1987 and 2004 with
      similar sensitivities to the Takahashi vaccine strain. The detection limit of RT
      LAMP was compared with that of RT-PCR using the Takahashi vaccine strain. We
      detected rubella virus genome material corresponding to 30 PFU/ml in a culture
      fluid sample by RT-LAMP within 60 min after the extraction of RNA with equal
      sensitivity to RT-nested PCR. The positive result rates of RT-LAMP, RT-PCR, and
      virus isolation were also compared using throat swabs obtained from patients who
      were clinically diagnosed with acute rubella virus infection in 2004 in Tochigi,
      Japan. Among nine patients with clinical rubella, the positive result rates were
      three/nine (33.3%) for virus isolation, six/nine (66.7%) for RT-PCR, and
      seven/nine (77.8%) for RT-LAMP. Consequently, RT-LAMP for rubella virus would be
      expected to be a reliable rapid diagnostic tool in the clinical setting.

PMID- 16954260
TI  - Fourier-transform infrared spectroscopic analysis is a powerful tool for studying
      the dynamic changes in Staphylococcus aureus small-colony variants.
AB  - Infections due to small-colony variants (SCVs) of Staphylococcus aureus in
      patients with chronic and recurrent infections are an emerging problem; however,
      studies with this subpopulation are hampered by the fact that SCVs may exhibit
      unstable phenotypes, making them difficult to study, particularly in broth media.
      In this study, two S. aureus sets comprising the (i) normal and the (ii) SCV
      phenotype (clonal with normal phenotype) recovered from clinical specimens, as
      well as (iii) corresponding site-directed mutants displaying the SCV phenotype
      (knockout of hemB) and (iv) their complemented mutants were examined by Fourier
      transform infrared (FTIR) spectroscopy. Phenotypes were defined on solid and in
      broth media. Using first-derivative infrared spectra to calculate spectral
      distances, hierarchical clustering based on spectral information resulted in a
      dendrogram with clear discrimination between SCV and normal phenotypes. The SCVs
      gave an FTIR fingerprint that was easily recognizable and that was much closer to
      other SCVs than to their parent strains. This technique offers for the first time
      a noninvasive approach to investigate dynamic processes of reversion of SCVs to
      the normal phenotype and vice versa. Thus, FTIR spectroscopy allowed a rapid and
      reproducible tool for the examination of different subpopulations of S. aureus on
      solid and in broth media for diagnostic and research purposes.

PMID- 16954261
TI  - Development of a PCR assay followed by nonradioactive hybridization using
      oligonucleotides covalently bound to CovaLink NH microwells for detection of four
      Plasmodium species in blood samples from humans.
AB  - We developed and evaluated a PCR-based assay to detect four Plasmodium species in
      79 blood samples from 56 travelers returning from areas where malaria is endemic.
      DNA amplification targeting a small region of the 18S rRNA gene was performed
      with Plasmodium genus-specific primers. The biotinylated PCR products were then
      identified by PCR-colorimetric Covalink NH microwell plate hybridization (CMPH)
      using species-specific phosphorylated probes covalently bound to a pretreated
      polystyrene surface. The results from PCR-CMPH showed high specificity, and for
      47 of the 56 patients (84%), microscopy and PCR-CMPH results were in agreement.
      Discordant results were reevaluated with microscopy examination, other molecular
      methods, and DNA sequencing. Except for one patient, discrepancies were resolved
      in favor of PCR-CMPH: three mixed infections were detected, four species
      identification errors were corrected, and two negative results were shown to be
      positive. Our results indicate that PCR-CMPH is a simple, rapid, and specific
      method for malaria diagnosis. It employs stable reagents and inexpensive
      equipment, making it suitable for routine epidemiological use.

PMID- 16954262
TI  - Rapid and sensitive detection of single cryptosporidium oocysts from archived
      glass slides.
AB  - In this study we report on the development and application of a novel method for
      efficiently extracting and detecting single Cryptosporidium oocysts from archived
      glass slides. Laser capture microscopy was used to extract low numbers of oocysts
      from archived glass slides. Highly sensitive real-time PCR methods were then
      developed to enable the rapid detection and identification of Cryptosporidium
      oocysts from these samples. The method was applied to fecal smears stained with a
      variety of standard oocyst stains and water samples. This application, with
      samples derived from both public health and water service laboratories,
      highlighted the strong potential of this method to be used as a rapid high
      throughput screening tool for the routine monitoring of Cryptosporidium and other
      medically important pathogens from clinical, veterinary, and environmental water
      samples. Importantly, the application of our protocol could be used to type
      Cryptosporidium and other pathogens from stored archived glass slides in public
      health and water service laboratories, providing vital epidemiological updates
      and helping to identify and trace pathogens and their routes of infection and
      ultimately improve their control.

PMID- 16954263
TI  - Highly effective detection of human papillomavirus 16 and 18 DNA by a testing
      algorithm combining broad-spectrum and type-specific PCR.
AB  - The use of a single broad-spectrum human papillomavirus (HPV) DNA-based PCR test
      may fail to detect lower concentrations of HPV DNA due to competition between
      different genotypes in mixed infections. To improve HPV detection by PCR, broad
      spectrum and type-specific (TS) PCRs were combined, with a focus on HPV-16 and
      HPV-18. Cervical and cervicovaginal cell samples were obtained from 1,113 healthy
      women (age range, 15 to 25 years) participating in an HPV-16/HPV-18 candidate
      vaccine efficacy trial. These samples were tested by a broad-spectrum SPF(10) PCR
      DNA enzyme immunoassay, followed by a primer SPF(10)-based line probe assay
      (SPF(10) LiPA), and HPV-16- and HPV-18-TS PCRs. The results for the majority of
      the HPV-16/18 SPF(10) LiPA-positive samples were confirmed by TS-PCR (kappa
      values, 0.775 for HPV-16 and 0.785 for HPV-18). However, TS PCR revealed
      additional positive samples among those that contained other HPV genotypes due to
      competition. Conversely, SPF(10) LiPA identified HPV-16 or -18 in samples that
      remained negative by TS PCR as a result of sampling variation. Analysis of follow
      up samples from more than 1,000 women confirmed that the combination of SPF(10)
      LiPA with additional HPV-16- and HPV-18-TS PCR diminishes the rate of false
      negative diagnosis. The combination of broad-spectrum and TS PCRs resulted in a
      novel testing algorithm. This combination of assays is more accurate than either
      method alone, and the novel algorithm offers a highly accurate and effective
      method for the analysis of HPV infections.

PMID- 16954264
TI  - High-throughput identification of clinical pathogenic fungi by hybridization to
      an oligonucleotide microarray.
AB  - Here we report the development of an oligonucleotide microarray method that can
      identify fungal pathogens in a single reaction. Specific oligonucleotide probes
      targeted to internal transcribed spacer 2 were designed and synthesized. Fungal
      DNA was amplified by universal primers, and the PCR product was hybridized with
      the oligonucleotide microarray. A series of specific hybridization profiles
      corresponding to species were obtained. The 122 strains of fungal pathogens,
      including standard and clinically isolated strains, used to test the specificity,
      stability, and sensitivity of the microarray system belonged to 20 species
      representing 8 genera. We found that the microarray system can successfully
      discriminate among the fungal pathogens to the species level, with high
      specificity and stability. The sensitivity was 15 pg/ml of DNA. This
      oligonucleotide microarray system represents a rapid, simple, and reliable
      alternative to conventional methods of identifying common clinical fungal
      isolates.

PMID- 16954266
TI  - Detection of cariogenic Streptococcus mutans in extirpated heart valve and
      atheromatous plaque specimens.
AB  - The involvement of oral bacteria in the pathogenesis of cardiovascular diseases
      has been the focus of attention in many studies, and several periodontal
      pathogens have been detected in diseased cardiovascular lesions, suggesting
      relationships between oral microorganisms and cardiovascular diseases. However,
      no information is available regarding the involvement of cariogenic pathogens
      such as Streptococcus mutans. The presence of oral streptococcal species and
      periodontitis-related bacteria in 35 heart valve and 27 atheromatous plaque
      clinical specimens, as well as 32 dental plaque specimens from the same subjects,
      was analyzed using a PCR method. Furthermore, broad-range PCR with DNA sequencing
      analysis was employed to identify the bacterial species in those samples.
      Streptococcus mutans was frequently detected in the heart valve (69%) and
      atheromatous plaque (74%) specimens, while other bacterial species, including
      those related to periodontitis, were detected with much lower frequencies. The
      bacterial composition in cardiovascular tissues was found to be markedly distinct
      from that in dental plaque, with only a limited number of species, including S.
      mutans, in the cardiovascular regions shown to have possibly originated from the
      oral cavity. Semiquantitative assay results revealed that S. mutans was detected
      in significant quantities in the heart valve (40%) and atheromatous plaque (48%)
      specimens, whereas the quantities of all other tested bacterial species,
      including several related to periodontitis, were negligible in the cardiovascular
      samples. These results indicate that S. mutans is a possible causative agent of
      cardiovascular disease.

PMID- 16954265
TI  - Comparison of transcription-mediated amplification and PCR assay results for
      various genital specimen types for detection of Mycoplasma genitalium.
AB  - Mycoplasma genitalium is now recognized as a possible cause of several idiopathic
      sexually transmitted disease (STD) syndromes. However, due to the difficulty of
      culture of this fastidious bacterium, nucleic acid amplification tests (NAATs)
      are necessary for its detection in patient specimens. In the current study we
      compared a newly developed research-only transcription-mediated amplification
      (TMA) assay (Gen-Probe Incorporated) to our in-house DNA-based PCR assay for
      detection of M. genitalium. The relative performance characteristics of these two
      NAATs were assessed with genital specimens from 284 women and 352 men reporting
      to an STD clinic in Seattle, WA. Among the women, M. genitalium was detected by
      the TMA and PCR assays in 36 (13%) and 39 (14%) vaginal swab specimens,
      respectively (kappa = 0.923); 26 (9%) and 23 (8%) cervical swab specimens,
      respectively (kappa = 0.843); and 25 (9%) and 28 (10%) urine specimens,
      respectively (kappa = 0.687). Among the M. genitalium-positive women, the
      relative sensitivities of detection for the TMA and PCR assays were 84% and 91%,
      respectively, for vaginal swab specimens; 60% and 53%, respectively, for cervical
      swab specimens; and 58% and 65%, respectively, for urine specimens. By using an
      infected patient (a woman positive at any site by TMA assay and at any site by
      PCR) as a proxy for a "gold standard," the specificities of detection were >99.5%
      for both the TMA and the PCR assays. Among the men, M. genitalium was detected in
      24 urine specimens (6.8%) by the TMA assay, 26 (7.4%) urine specimens by PCR
      assay, and 32 urine specimens (9%) by either test (kappa = 0.791). We conclude
      that the M. genitalium TMA and PCR assays are highly specific and that vaginal
      swab specimens are the most sensitive specimen type for the detection of M.
      genitalium in women.

PMID- 16954267
TI  - Prevalence of newer beta-lactamases in gram-negative clinical isolates collected
      in the United States from 2001 to 2002.
AB  - Newer beta-lactamases such as extended-spectrum beta-lactamases (ESBLs),
      transferable AmpC beta-lactamases, and carbapenemases are associated with
      laboratory testing problems of false susceptibility that can lead to
      inappropriate therapy for infected patients. Because there appears to be a lack
      of awareness of these enzymes, a study was conducted during 2001 to 2002 in which
      6,421 consecutive, nonduplicate clinical isolates of aerobically growing gram
      negative bacilli from patients at 42 intensive care unit (ICU) and 21 non-ICU
      sites across the United States were tested on-site for antibiotic susceptibility.
      From these isolates, 746 screen-positive isolates (11.6%) were referred to a
      research facility and investigated to determine the prevalence of ESBLs in all
      gram-negative isolates, transferable AmpC beta-lactamases in Klebsiella
      pneumoniae, and carbapenemases in Enterobacteriaceae. The investigations involved
      phenotypic tests, isoelectric focusing, beta-lactamase inhibitor studies,
      spectrophotometric assays, induction assays, and molecular analyses. ESBLs were
      detected only in Enterobacteriaceae (4.9% of all Enterobacteriaceae) and were
      found in species other than those currently recommended for ESBL testing by the
      CLSI (formerly NCCLS). These isolates occurred at 74% of the ICU sites and 43% of
      the non-ICU sites. Transferable AmpC beta-lactamases were detected in 3.3% of K.
      pneumoniae isolates and at 16 of the 63 sites (25%) with no difference between
      ICU and non-ICU sites. Three sites submitted isolates that produced class A
      carbapenemases. No class B or D carbapenemases were detected. In conclusion,
      organisms producing ESBLs and transferable AmpC beta-lactamases were widespread.
      Clinical laboratories must be able to detect important beta-lactamases to ensure
      optimal patient care and infection control.

PMID- 16954268
TI  - Real-time PCR assay for detection and quantification of hepatitis B virus
      genotypes A to G.
AB  - The detection and quantification of hepatitis B virus (HBV) DNA play an important
      role in diagnosing and monitoring HBV infection as well as assessing therapeutic
      response. The great variability among HBV genotypes and the enormous range of
      clinical HBV DNA levels present challenges for PCR-based amplification
      techniques. In this study, we describe the development, evaluation, and
      validation of a novel real-time PCR assay designed to provide accurate
      quantification of DNA from all eight HBV genotypes in patient plasma specimens. A
      computer algorithm was used to design degenerate real-time PCR primers and probes
      based upon a large number (n = 340) of full-length genomic sequences including
      HBV genotypes A to H from Europe, Africa, Asia, and North and South America.
      Genotype performance was tested and confirmed using 59 genotype A to G specimens
      from two commercially available worldwide genotype panels. This assay has a
      dynamic range of at least 8 log(10) without the need for specimen dilution, good
      clinical intra- and interassay precision, and excellent correlation with the
      Bayer Diagnostics VERSANT HBV DNA 3.0 (branched DNA) assay (r = 0.93). Probit
      analysis determined the 95% detection level was 56 IU/ml, corresponding to 11
      copies per PCR well. The high sensitivity, wide linear range, good
      reproducibility, and genotype inclusivity, combined with a small sample volume
      requirement and low cost, make this novel quantitative HBV real-time PCR assay
      particularly well suited for application to large clinical and epidemiological
      studies.

PMID- 16954269
TI  - Staphylococcus aureus throat colonization is more frequent than colonization in
      the anterior nares.
AB  - The aim of this study was to determine the frequency and persistence of
      Staphylococcus aureus carriage in the throat in relation to anterior naris
      carriage. By use of a sensitive enrichment broth, S. aureus was cultured from the
      two sites from 259 patients upon admission to an orthopedic ward and from 87
      staff members of the same ward. The throat was the most common carriage site in
      both groups. Forty percent of the patients and 54% of the staff were positive for
      S. aureus in the throat, compared to 31% and 36%, respectively, in the anterior
      nares. To determine the persistence of carriage, 67 individuals were repeatedly
      sampled from the anterior nares and the throat over 2 years (5 to 10 sampling
      occasions; mean, 7.8). The majority, 58% (39/67), were defined as persistent
      carriers of S. aureus, considering culture results from both sites. Of the 39
      persistent carriers, 15 individuals were culture positive from only the throat on
      more than half of the sampling occasions (these are called preferential throat
      carriers) while only 5% (two individuals) were preferential anterior naris
      carriers by use of the same definition. Typing of the collected S. aureus
      isolates by pulsed-field gel electrophoresis revealed that the same strain of S.
      aureus was present, over time, in the throat of an individual at least to the
      same extent as in the anterior nares. Throat carriage was at least as persistent
      as carriage in the anterior nares.

PMID- 16954270
TI  - Evaluation of the new chromogenic medium Candida ID 2 for isolation and
      identification of Candida albicans and other medically important Candida species.
AB  - The usefulness of Candida ID 2 (CAID2) reformulated medium (bioMerieux, France)
      has been compared with that of the former Candida ID (CAID; bioMerieux), Albicans
      ID 2 (ALB2; bioMerieux), and CHROMagar Candida (CAC; Chromagar, France)
      chromogenic media for the isolation and presumptive identification of clinically
      relevant yeasts. Three hundred forty-five stock strains from culture collections,
      and 103 fresh isolates from different clinical specimens were evaluated. CAID2
      permitted differentiation based on colony color between Candida albicans (cobalt
      blue; sensitivity, 91.7%; specificity, 97.2%) and Candida dubliniensis (turquoise
      blue; sensitivity, 97.9%; specificity, 96.6%). Candida tropicalis gave
      distinguishable pink-bluish colonies in 97.4% of the strains in CAID2
      (sensitivity, 97.4%; specificity, 100%); the same proportion was reached in CAC,
      where colonies were blue-gray (sensitivity, 97.4%; specificity, 98.7%). CAC and
      CAID2 showed 100% sensitivity values for the identification of Candida krusei.
      However, with CAID2, experience is required to differentiate the downy aspect of
      the white colonies of C. krusei from other white-colony-forming species. The new
      CAID2 medium is a good candidate to replace CAID and ALB2, and it compares well
      to CAC for culture and presumptive identification of clinically relevant Candida
      species. CAID2 showed better results than CAC in some aspects, such as quicker
      growth and color development of colonies from clinical specimens, detection of
      mixed cultures, and presumptive differentiation between C. albicans and C.
      dubliniensis.

PMID- 16954271
TI  - As a bacterial culture medium, citrated sheep blood agar is a practical
      alternative to citrated human blood agar in laboratories of developing countries.
AB  - Human blood agar (HuBA) is widely used in developing countries for the isolation
      of bacteria from clinical specimens. This study compared citrated sheep blood
      agar (CSBA) and HuBA with defibrinated horse blood agar and defibrinated sheep
      blood agar (DSBA) for the isolation and antibiotic susceptibility testing of
      reference and clinical strains of Streptococcus pneumoniae, Streptococcus
      pyogenes, and Staphylococcus aureus. Reference and clinical strains of all
      organisms were diluted in brain heart infusion and a clinical specimen of
      cerebrospinal fluid and cultured on all agars. Viable counts, colony morphology,
      and colony size were recorded. Susceptibility testing for S. pneumoniae and S.
      pyogenes was performed on defibrinated sheep blood Mueller-Hinton agar, citrated
      sheep blood Mueller-Hinton agar (CSB MHA), and human blood Mueller-Hinton agar
      plates. For all organisms, the colony numbers were similar on all agars.
      Substantially smaller colony sizes and absent or minimal hemolysis were noted on
      HuBA for all organisms. Antibiotic susceptibility results for S. pneumoniae were
      similar for the two sheep blood agars; however, larger zone sizes were displayed
      on HuBA, and quality control for the reference strain failed on HuBA. For S.
      pyogenes, larger zone sizes were demonstrated on HuBA and CSBA than on DSBA. Poor
      hemolysis made interpretation of the zone sizes difficult on HuBA. CSBA is an
      acceptable alternative for the isolation of these organisms. The characteristic
      morphology is not evident, and hemolysis is poor on HuBA; and so HuBA is not
      recommended for use for the isolation or the susceptibility testing of any of
      these organisms. CSB MHA may be suitable for use for the susceptibility testing
      of S. pneumoniae.

PMID- 16954272
TI  - Characterization of Bacillus cereus isolates associated with fatal pneumonias:
      strains are closely related to Bacillus anthracis and harbor B. anthracis
      virulence genes.
AB  - Bacillus cereus is ubiquitous in nature, and while most isolates appear to be
      harmless, some are associated with food-borne illnesses, periodontal diseases,
      and other more serious infections. In one such infection, B. cereus G9241 was
      identified as the causative agent of a severe pneumonia in a Louisiana welder in
      1994. This isolate was found to harbor most of the B. anthracis virulence plasmid
      pXO1 (13). Here we report the characterization of two clinical and one
      environmental B. cereus isolate collected during an investigation of two fatal
      pneumonia cases in Texas metal workers. Molecular subtyping revealed that the two
      cases were not caused by the same strain. However, one of the three isolates was
      indistinguishable from B. cereus G9241. PCR analysis demonstrated that both
      clinical isolates contained B. anthracis pXO1 toxin genes. One clinical isolate
      and the environmental isolate collected from that victim's worksite contained the
      cap A, B, and C genes required for capsule biosynthesis in B. anthracis. Both
      clinical isolates expressed a capsule; however, neither was composed of poly-D
      glutamic acid. Although most B. cereus isolates are not opportunistic pathogens
      and only a limited number cause food-borne illnesses, these results demonstrate
      that some B. cereus strains can cause severe and even fatal infections in
      patients who appear to be otherwise healthy.

PMID- 16954273
TI  - Quinupristin-dalfopristin resistance in Enterococcus faecium isolates from
      humans, farm animals, and grocery store meat in the United States.
AB  - Three hundred sixty-one quinupristin-dalfopristin (Q-D)-resistant Enterococcus
      faecium (QDREF) isolates were isolated from humans, turkeys, chickens, swine,
      dairy and beef cattle from farms, chicken carcasses, and ground pork from grocery
      stores in the United States from 1995 to 2003. These isolates were evaluated by
      pulsed-field gel electrophoresis (PFGE) to determine possible commonality between
      QDREF isolates from human and animal sources. PCR was performed to detect the
      streptogramin resistance genes vatD, vatE, and vgbA and the macrolide resistance
      gene ermB to determine the genetic mechanism of resistance in these isolates.
      QDREF from humans did not have PFGE patterns similar to those from animal
      sources. vatE was found in 35%, 26%, and 2% of QDREF isolates from turkeys,
      chickens, and humans, respectively, and was not found in QDREF isolates from
      other sources. ermB was commonly found in QDREF isolates from all sources. Known
      streptogramin resistance genes were absent in the majority of isolates,
      suggesting the presence of other, as-yet-undetermined, mechanisms of Q-D
      resistance.

PMID- 16954274
TI  - Relevance of influenza a virus detection by PCR, shell vial assay, and tube cell
      culture to rapid reporting procedures.
AB  - Influenza A virus was detected at higher rates and for more extended time periods
      with real-time PCR than with cell cultures. We show here that, using the
      theranostic approach, rapid viral detection and reporting can provide for early
      implementation and assessment of available antiviral therapy.

PMID- 16954275
TI  - Nosocomial spread of Enterococcus faecium resistant to vancomycin and linezolid
      in a tertiary care medical center.
AB  - In May 2004 our institution encountered its first clinical isolate of linezolid
      resistant, vancomycin-resistant Enterococcus faecium (LRVRE). Between October
      2004 and July 2005, 40 patients from whom LRVRE organisms were recovered in
      clinical specimens were characterized. Epidemiologic investigation and pulsed
      field gel electrophoresis patterns indicated a clonal outbreak related to
      nosocomial spread.

PMID- 16954276
TI  - Molecular epidemiology of adenovirus isolates from patients diagnosed with
      intussusception in Melbourne, Australia.
AB  - Twenty-one intussusception (IS)-associated and 59 temporally linked adenoviral
      isolates from clinical infections were compared. Species C (15/21 IS- and 32/59
      non-IS-associated isolates) dominated. Of these, serotype 2 (AdV-2) (7/15 IS
      associated isolates) and serotype 1 (AdV-1) (16/32 non-IS-associated isolates)
      were the most commonly identified serotypes. DNA restriction analysis of AdV-2
      isolates identified six genomic types; of these, type D2 (3/7 IS- and 8/11 non-IS
      associated isolates) was the dominant type after BamHI and SmaI digestion. IS
      associated isolates are similar to circulating non-IS-associated strains.

PMID- 16954277
TI  - Comparison of tests to detect oxacillin resistance in Staphylococcus intermedius,
      Staphylococcus schleiferi, and Staphylococcus aureus isolates from canine hosts.
AB  - Multiple tests were compared to the reference standard PBP2a latex agglutination
      test for detection of mecA-mediated oxacillin resistance in canine staphylococci.
      Cefoxitin disk diffusion, using breakpoints for human isolates of coagulase
      negative Staphylococcus spp., had low sensitivity for detection of oxacillin
      resistance in members of the Staphylococcus intermedius group.

PMID- 16954278
TI  - Molecular differentiation of Treponema pallidum subspecies.
AB  - Treponema pallidum includes three subspecies of antigenically highly related
      treponemes. These organisms cause clinically distinct diseases and cannot be
      distinguished by any existing test. In this report, genetic signatures are
      identified in two tpr genes which, in combination with the previously published
      signature in the 5' flanking region of the tpp15 gene, can differentiate the T.
      pallidum subspecies, as well as a simian treponeme.

PMID- 16954279
TI  - Peptide nucleic acid fluorescence in situ hybridization-based identification of
      Candida albicans and its impact on mortality and antifungal therapy costs.
AB  - The impact of rapid identification of Candida albicans blood isolates by peptide
      nucleic acid fluorescence in situ hybridization (PNA FISH) on the selection and
      expenditure of antifungal therapy was evaluated. PNA FISH was 100% sensitive and
      specific in the rapid identification of 31 out of 72 candidemias as C. albicans
      and resulted in a significant reduction of caspofungin usage, with an overall
      cost savings of 1,729 US dollars per patient.

PMID- 16954280
TI  - Performance of human immunodeficiency virus type 1 gp41 assays for detecting
      enfuvirtide (T-20) resistance mutations.
AB  - The performance of a gp41 assay, created using reagents designed for use with the
      OpenGene DNA Sequencing System, was evaluated using a panel of plasma samples
      obtained from enfuvirtide-naive and -experienced human immunodeficiency virus
      type 1-infected subjects. Resulting sequence data were highly accurate compared
      to a "home brew" assay and clonal sequence analysis.

PMID- 16954281
TI  - Comparison of API 20E and invA PCR for identification of Salmonella enterica
      isolates from swine production units.
AB  - API 20E and invA PCR were evaluated for the identification of Salmonella enterica
      isolates from swine farms. API 20E had the highest agreement with other tests at
      the 99.9% likelihood level. Both tests had 100% sensitivity and 96% specificity
      compared to 16S rRNA sequencing. Compared to serotyping, both tests had 96%
      sensitivity; specificity was 86% for API 20E and 79% for invA PCR.

PMID- 16954282
TI  - Spread of cholera with newer clones of Vibrio cholerae O1 El Tor, serotype inaba,
      in India.
AB  - During 2004 and 2005, cholera was recorded in 15 states of India, with 7
      outbreaks. The newly emerged Vibrio cholerae O1 Inaba had a different antibiogram
      and ribotype, different pulsotypes, and different mutations in the wbeT gene. Due
      to the absence of serogroup O139, the Inaba serotype may have acquired the
      potential to affect the population at large.

PMID- 16954283
TI  - Diagnostic value of reverse transcription-PCR for detection of cytomegalovirus
      pp67 in samples from solid-organ transplant recipients.
AB  - We evaluated a highly sensitive quantitative real-time one-step reverse
      transcription-PCR (RT-PCR) for detection of human cytomegalovirus pp67
      transcripts in monitoring of solid-organ transplant recipients. Results were
      compared with those of pp65 antigen testing and quantitative DNA-PCR. Due to a
      low clinical sensitivity, the pp67 RT-PCR was not able to replace these assays.

PMID- 16954284
TI  - Differential in vitro expression of the brkA gene in Bordetella pertussis and
      Bordetella parapertussis clinical isolates.
AB  - In this study, we set up a real-time reverse transcriptase PCR assay to measure
      the relative amounts of brkA transcripts in 50 Bordetella isolates. The results
      suggested that brkA expression is strain dependent and its level may play a role
      in determining the serum resistance or susceptibility phenotype. Pertussis
      immunocompetent sera were unable to kill Bordetella parapertussis via complement
      deposition.

PMID- 16954285
TI  - Clonal relationship among Vibrio cholerae O1 El Tor strains causing the largest
      cholera epidemic in Kenya in the late 1990s.
AB  - Eighty Vibrio cholerae O1 strains selected to represent the 1998-to-1999 history
      of the largest cholera epidemic in Kenya were characterized by ribotyping,
      antimicrobial susceptibility, and random amplified polymorphic DNA patterns.
      Except for 19 strains from 4 local outbreaks in North Eastern Province along the
      Somalia border, the other 61 strains from 25 outbreaks occurring in districts
      scattered around the country were all ribotype B27 and resistant to
      chloramphenicol, spectinomycin, streptomycin, sulfamethoxazole, and trimethoprim.
      The 61 strains showed similar and specific amplified DNA patterns. These findings
      indicate that the predominant strains that caused the Kenyan epidemic had a
      clonal origin and suggest that ribotype B27 strains, which first appeared in West
      Africa in 1994, have had a rapid spread to eastern Africa.

PMID- 16954286
TI  - Molecular epidemiology of multidrug-resistant Mycobacterium bovis isolates with
      the same spoligotyping profile as isolates from animals.
AB  - PCR-based characterization techniques have been adopted in most laboratories for
      Mycobacterium bovis typing. We report a molecular characterization of human
      multidrug-resistant M. bovis isolates and three bovine isolates that share the
      spoligotyping profile. The analysis of the direct repeat region showed that both
      groups differed in the presence of spacers not included in the current membrane.
      They were also distinguished by two out of the nine mycobacterial interspersed
      repetitive unit variable-number tandem repeat loci tested, indicating that the
      human infection was not acquired from the cattle from which isolates were
      obtained. These results highlight that a combination of techniques is required
      for appropriate discrimination, even for those spoligotypes that have a low
      frequency.

PMID- 16954287
TI  - rpoB Gene mutations and molecular characterization of rifampin-resistant
      Mycobacterium tuberculosis isolates from Shandong Province, China.
AB  - Sixty rifampin (RIF)-resistant and 75 RIF-susceptible Mycobacterium tuberculosis
      isolates from Shandong Province, China, were analyzed for rpoB gene mutations and
      genotyped. Mycobacterial interspersed repetitive unit (MIRU) genotype
      223325173533 was overrepresented among RIF-resistant isolates. MIRU combined with
      IS6110 restriction fragment length polymorphism analysis as the second-line
      genotyping method may reflect epidemiologic links more reliably than each method
      alone.

PMID- 16954288
TI  - Clinical significance of coagulase-negative staphylococci recovered from
      nonsterile sites.
AB  - Laboratory criteria were used to select coagulase-negative staphylococci isolated
      from nonsterile body sites for further investigation. Fifty-seven percent of the
      study isolates were clinically significant, predominantly causing community
      acquired soft tissue infections. There were species-related differences in
      virulence, with 91% of Staphylococcus lugdunensis isolates clinically significant
      compared with 11% of S. haemolyticus isolates.

PMID- 16954289
TI  - Fluorescence in situ hybridization for rapid identification of Achromobacter
      xylosoxidans and Alcaligenes faecalis recovered from cystic fibrosis patients.
AB  - Achromobacter xylosoxidans is frequently isolated from the respiratory secretions
      of cystic fibrosis (CF) patients, but identification with biochemical tests is
      unreliable. We describe fluorescence in situ hybridization assays for the rapid
      identification of Achromobacter xylosoxidans and Alcaligenes faecalis. Both
      assays showed high sensitivities and high specificities with a collection of 155
      nonfermenters from CF patients.

PMID- 16954290
TI  - Effectiveness of cephalosporins in the sputum of patients with nosocomial
      bronchopneumonia.
AB  - Nosocomial bronchopneumonia is a frequent complication in patients with chronic
      intratracheal intubation. Despite targeted antibiotic treatment, production of
      abundant bronchial secretion containing pathogen bacteria often tends to be
      chronic, and so mortality drastically increases. This problem led to an
      investigation of the penetration of five cephalosporin antibiotics into the
      sputum. Serum and sputum were collected from 24 chronically intubated patients
      having purulent nosocomial bronchopneumonia treated in an intensive care unit
      (ICU). Patients received the following doses intravenously every 24 h: five
      received 70 mg/kg of body weight cefuroxime, four received 110 mg/kg cefamandole,
      six received 80 mg/kg ceftriaxone, four received 80 mg/kg ceftazidime, and five
      received 80 mg/kg cefepime. Antibiotic concentrations in the serum and sputum
      were evaluated by capillary electrophoresis. MICs were determined for bacteria
      isolated from the purulent bronchial secretions. The mean levels of the
      cephalosporins in the sputum did not reach the MICs for the bacteria isolated
      from the same samples. Ceftriaxone was the only one of the investigated five
      cephalosporins that had a measurable concentration in the sputum (1.4 +/- 1.2
      mg/liter). The low concentration of antibiotics in the purulent tracheobronchial
      secretion can be one of the many reasons for ineffective therapy of nosocomial
      bronchopneumonia in intubated patients in the ICUs. In the case of intubated or
      mechanically ventilated patients having chronic bronchopneumonia, determination
      of drug concentration in the bronchial secretion might be considered when
      selecting an antibiotic for treatment.

PMID- 16954291
TI  - Antibiotic susceptibility and molecular diversity of Bacillus anthracis strains
      in Chad: detection of a new phylogenetic subgroup.
AB  - We genotyped 15 Bacillus anthracis isolates from Chad, Africa, using multiple
      locus variable-number tandem repeat analysis and three additional direct-repeat
      markers. We identified two unique genotypes that represent a novel genetic
      lineage in the A cluster. Chadian isolates were susceptible to 11 antibiotics and
      free of 94 antibiotic resistance genes.

PMID- 16954292
TI  - Capsule production in Bacillus cereus strains associated with severe pneumonia.
AB  - We identified three encapsulated Bacillus cereus strains, isolated from patients
      with severe pneumonia, in a collection of B. cereus isolates associated with
      human illness. We found that the extent of capsule expression was influenced by
      culturing conditions. Our findings highlight consequent clinical and laboratory
      diagnostic challenges posed by such isolates.

PMID- 16954293
TI  - A modified Christensen's urea and CLSI broth microdilution method for testing
      susceptibilities of six Malassezia species to voriconazole, itraconazole, and
      ketoconazole.
AB  - Two supplemented broths (Christensen's urea with 0.1% Tween 80 and 0.5% Tween 40
      and RPMI 1640 with 1% glycerol, 1% peptone, 1.8% glucose, and 0.05% Tween 80)
      were evaluated to determine voriconazole, itraconazole, and ketoconazole MICs for
      200 Malassezia sp. isolates. Malassezia globosa and M. restricta were the least
      susceptible species (MICs at which 90% of the isolates tested were inhibited, 1
      to >or=8 microg/ml versus 0.25 to 1 microg/ml).

PMID- 16954294
TI  - Aspergillus galactomannan enzyme-linked immunosorbent assay cross-reactivity
      caused by invasive Geotrichum capitatum.
AB  - We report three cases of invasive Geotrichum capitatum infection in patients with
      acute leukemia for which an enzyme-linked immunosorbent assay (ELISA) for
      Aspergillus galactomannan was positive, with no evidence of aspergillosis.
      Supernatants obtained from suspensions of 17 G. capitatum strains gave positive
      reactions with the Aspergillus galactomannan ELISA. These clinical and laboratory
      data seem to suggest that G. capitatum produces a soluble antigen that is cross
      reactive with Aspergillus galactomannan.

PMID- 16954295
TI  - Detection of hepatitis B virus (HBV) genotype E carried--even in the presence of
      high titers of anti-HBs antibodies--by an Argentinean patient of African descent
      who had received vaccination against HBV.
AB  - Genotype E hepatitis B virus (HBV) was detected in two Argentine sisters
      exhibiting an African mitochondrial lineage. One of them (who had been vaccinated
      against HBV) exhibited anti-HBs cocirculating antibodies without HBsAg escape
      mutants, while her unvaccinated sister showed a D144A HBsAg escape mutant without
      anti-HBs antibodies. Both sisters carried an unusual L209V substitution within
      HBsAg.

PMID- 16954296
TI  - Identification of genotype 1 hepatitis E virus in samples from swine in Cambodia.
AB  - Hepatitis E virus (HEV) is a major enterically transmitted pathogen in many
      developing countries, where it causes outbreaks and sporadic cases of acute
      hepatitis. A study conducted with pigs from several livestock farms in Cambodia
      identified one swine genotype 1 HEV isolate as being associated with prevalent
      swine genotype 3 HEV.

PMID- 16954297
TI  - Invader plus method detects herpes simplex virus in cerebrospinal fluid and
      simultaneously differentiates types 1 and 2.
AB  - We report here on the development and validation of a prototype Invader Plus
      method for the qualitative detection of herpes simplex virus types 1 and 2 in
      cerebrospinal fluid (CSF). The method combines PCR and Invader techniques in a
      single, closed-tube, continuous-reaction format that gives an analytical
      sensitivity of approximately 10 copies per reaction. The clinical sensitivity and
      specificity were 100.0% and 98.6%, respectively, when the results of the method
      were validated against the results obtained with a PCR colorimetric microtiter
      plate system by use of clinical CSF specimens.

PMID- 16954299
TI  - Diagnosis of gastric syphilis by direct immunofluorescence staining and real-time
      PCR testing.
AB  - We report on a case of gastric syphilis in a patient with chronic dyspepsia. The
      diagnosis was established by serology and the demonstration of spirochetes in
      diffusely inflammed gastric mucosa by staining with a fluorescent monoclonal
      antibody specific for pathogenic treponemes and by the detection of specific
      treponemal DNA sequences by a real-time PCR.

PMID- 16954298
TI  - Mycobacterium tuberculosis complex and mycobacterial heat shock proteins in lymph
      node tissue from patients with pulmonary sarcoidosis.
AB  - We demonstrated that not whole Mycobacterium tuberculosis but its particular
      antigens, hsp70(Mtb), hsp65(Mtb), and hsp16(Mtb), are present in lymph node
      tissues of patients with sarcoidosis (SA). hsp16(Mtb) occurs in the early stage
      of SA, whereas hsp70(Mtb) occurs in stage II of SA. hsp65(Mtb) is highly
      expressed in the capillary vessels in lymph node tissues in patients with SA.

PMID- 16954300
TI  - Abdominal aortic aneurysm infected by Yersinia pseudotuberculosis.
AB  - Infected aneurysms caused by Yersinia are very uncommon and are principally due
      to Yersinia enterocolitica. We describe the first case of an infected aneurysm
      caused by Yersinia pseudotuberculosis in an elderly patient with a history of
      atherosclerotic cardiovascular disease.

PMID- 16954301
TI  - Pulmonary cholera due to infection with a non-O1 Vibrio cholerae strain.
AB  - We present 2 cases of primary pulmonary non-O1 Vibrio cholerae infection. We
      believe that these are the first documented cases of primary pulmonary infection
      due to this organism from a freshwater source.

PMID- 16954302
TI  - Ventilator-associated pneumonia caused by Dolosigranulum pigrum.
AB  - Dolosigranulum pigrum is an unusual gram-positive catalase-negative coccus. It
      was isolated, only after prolonged incubation, from bronchial secretions from a
      patient with ventilator-associated pneumonia. The patient responded well to
      antimicrobial therapy. Identification was done by 16S rRNA DNA sequence analysis,
      but it can be done with relatively simple phenotypic tests.

PMID- 16954303
TI  - Hip prosthesis infection due to Mycobacterium wolinskyi.
AB  - Mycobacterium wolinskyi, first described in 1999, is a rapidly growing
      mycobacterium related to the Mycobacterium smegmatis group. Only eight cases of
      infection due to this microorganism have been reported, including three cases of
      bone infection. Here, we present the first case of a joint prosthesis infection
      cured with the combination of surgery and prolonged antibiotic therapy. The
      microorganism was identified by biochemical tests and 16S rRNA and Hsp65 gene
      sequence analysis.

PMID- 16954304
TI  - Two cases of infections due to multidrug-resistant Bacteroides fragilis group
      strains.
AB  - Bacteroides fragilis group strains are still considered susceptible to most
      antimicrobial agents used for the treatment of infections caused by anaerobic
      organisms. We describe two cases of infections due to isolates simultaneously
      resistant to clindamycin, tetracycline, cefoxitin, piperacillin-tazobactam, and
      imipenem and, in one of the two cases, to metronidazole. Such infections,
      although still rare, do exist and tend to complicate treatment.

PMID- 16954305
TI  - Circulation of incorrectly labeled adenovirus 50 and 51 prototype preparations.

PMID- 16954306
TI  - 16S rRNA gene sequencing and the routine clinical microbiology laboratory: a
      perfect marriage?

PMID- 16954307
TI  - The effectiveness and efficiency of home-based nursing health promotion for older
      people: a review of the literature.
AB  - Despite the large potential role that community nurses have in providing
      individualized health promotion to older people, there is a lack of consensus in
      the literature regarding this role's effectiveness and efficiency. This article
      presents a literature review and synthesis of 12 randomized controlled trials
      selected from 344 published studies on preventive home visitation programs for
      older people. The findings suggest that a diversity of home visiting
      interventions carried out by nurses can favorably affect health and functional
      status, mortality rates, use of hospitalization and nursing homes, and costs.
      Further research is needed that focuses on the outcomes of quality of life,
      mental health, social support, caregiver burden, the acceptability of
      intervention, and specific subgroups of clients who benefit most. Findings also
      indicate the need for a theoretical foundation, increased emphasis on health
      promotion strategies, and more research using a more complete economic evaluation
      to establish efficiency.

PMID- 16954308
TI  - The effectiveness of screening for obesity in primary care: weighing the
      evidence.
AB  - In response to growing alarm about the increase in the prevalence of obesity in
      the United States, several organizations have recommended that physicians screen
      their adult patients for this condition and initiate treatment. Screening can be
      an effective intervention when the condition is grave and prevalent, when an
      accurate test exists, when effective treatment exists, when the screening program
      itself does not pose undue risks, and when early detection and treatment improve
      outcomes. This article critically reviews the evidence supporting these criteria
      in the case of obesity in adults. It extends previous reviews by assessing the
      potential impact that uncertainties in the evidence base may have on the
      effectiveness a screening program. It also examines the feasibility of such a
      program. We conclude that following the recommendation to screen all adults for
      obesity is unlikely to improve outcomes.

PMID- 16954309
TI  - Using propensity stratification to compare patient outcomes in hospital-based
      versus freestanding skilled-nursing facilities.
AB  - Medicare skilled-nursing facility (SNF) patients exhibit differences in resource
      use and outcomes by whether the SNF is hospital-based or freestanding. Some of
      the differences may be attributable to patient selection rather than underlying
      institutional differences. This study adjusts for patient selection by
      stratifying Medicare SNF patients by their likelihood of hospital-based SNF
      referral. Three outcomes are analyzed to illustrate this approach: Medicare SNF
      length of stay, discharge to home within 30 days, and preventable hospital
      readmissions. The estimations use claims and patient-assessment data merged with
      facility and market characteristics. The results provide strong evidence that
      good candidates for faster recovery and discharge to the community are
      preferentially selected into hospital-based units. While the unstratified
      regression approach controls for much of the selection, stratified regressions
      provide further reductions in setting-specific differences. Remaining differences
      may be because of patterns of care or reflect residual bias from unobserved
      factors.

PMID- 16954310
TI  - What happens to children who lose public health insurance coverage?
AB  - Little is known about what happens to children who disenroll from public health
      insurance programs. A telephone survey was conducted of children who recently had
      disenrolled from either Oregon's State Children's Health Insurance Program
      (SCHIP) or FHIAP (premium assistance) programs, both of which have identical
      eligibility requirements. Access for these disenrolled children was driven
      largely by health insurance coverage. Insured children were more likely to have a
      usual source of care and to have seen a physician when they needed one. While
      FHIAP-disenrolled children were more likely to have private health-insurance
      coverage than those leaving SCHIP, absolute levels were low (53 percent and 33
      percent, respectively). Thus, these programs generally did not provide a bridge
      to nonsubsidized private health insurance. Despite higher incomes (the main
      reason for losing coverage), many families did not purchase private health
      insurance, presumably because they still could not afford to do so.

PMID- 16954311
TI  - Development and validation of a patient-reported measure of physician cultural
      competency.
AB  - While cultural competency is widely promoted, the lack of a measure of cultural
      competency limits our ability to evaluate interventions and to understand the
      effects of cultural competency on health care quality. Based on a conceptual
      framework of cultural competency derived from expert focus groups, we developed a
      patient-reported measure of physician culturally competent communication
      behaviors that we validated in a group of 429 adult primary-care patients with
      diabetes and/or hypertension and their 53 physicians. Construct validity was
      supported by a moderate association with both patient satisfaction (r = .32, p <
      .001) and patient trust (r = .53, p < .001). Predictive validity was supported by
      an association with a decrease in blood pressure among hypertensive patients (r =
      -.18; p < .05). This new measure may be useful in assessing levels of culturally
      competent provider behavior and investigating associations between provider
      cultural competency and health care processes and outcomes.

PMID- 16954312
TI  - Impact of sample size on the performance of multiple-model pharmacokinetic
      simulations.
AB  - Monte Carlo simulations are increasingly used to predict pharmacokinetic
      variability of antimicrobials in a population. We investigated the sample size
      necessary to provide robust pharmacokinetic predictions. To obtain reasonably
      robust predictions, a nonparametric model derived from a sample population size
      of >/=50 appears to be necessary as the input information.

PMID- 16954313
TI  - Methodological issues in the assessment of antimalarial drug treatment: analysis
      of 13 studies in eight African countries from 2001 to 2004.
AB  - The objectives of these analyses were to assess the feasibility of the latest WHO
      recommendations (28-day follow-up with PCR genotyping) for the assessment of
      antimalarial drug efficacy in vivo and to examine how different statistical
      approaches affect results. We used individual-patient data from 13 studies of
      uncomplicated pediatric falciparum malaria conducted in sub-Saharan Africa, using
      chloroquine (CQ), sulfadoxine/pyrimethamine (SP), or amodiaquine (AQ). We
      assessed the use effectiveness and test performance of PCR genotyping in
      distinguishing recurrent infections. In analyzing data, we compared (i) the risk
      of failure on target days (days 14 and 28) by using Kaplan-Meier and per-protocol
      evaluable patient analyses, (ii) PCR-corrected results allowing (method 1) or
      excluding (method 2) new infections, (iii) and day 14 versus day 28 results. Of
      the 2,576 patients treated, 2,287 (89%) were evaluable on day 28. Of the 695
      recurrences occurring post-day 14, 650 could be processed and 584 were resolved
      (PCR use effectiveness, 84%; test performance, 90%). The risks of failure on day
      28 with Kaplan-Meier and evaluable-patient analyses tended to be generally close
      (except in smaller studies) because the numbers of dropouts were minimal, but
      attrition rates on day 28 were higher with the latter method. Method 2 yielded
      higher risks of failure than method 1. Extending observation to 28 days produced
      higher estimated risks of failure for SP and AQ but not for CQ (high failure
      rates by day 14). Results support the implementation of the current WHO protocol
      and favor analyzing PCR-corrected outcomes by Kaplan-Meier analysis (which allows
      for dropouts) and retaining new infections (which minimizes losses).

PMID- 16954314
TI  - Unexpected link between iron and drug resistance of Candida spp.: iron depletion
      enhances membrane fluidity and drug diffusion, leading to drug-susceptible cells.
AB  - Inthis study, we show that iron depletion in Candida albicans with
      bathophenanthrolene disulfonic acid and ferrozine as chelators enhanced its
      sensitivity to several drugs, including the most common antifungal, fluconazole
      (FLC). Several other species of Candida also displayed increased sensitivity to
      FLC because of iron restriction. Iron uptake mutations, namely, Deltaftr1 and
      Deltaftr2, as well as the copper transporter mutation Deltaccc2, which affects
      high-affinity iron uptake in Candida, produced increased sensitivity to FLC
      compared to that of the wild type. The effect of iron depletion on drug
      sensitivity appeared to be independent of the efflux pump proteins Cdr1p and
      Cdr2p. We found that iron deprivation led to lowering of membrane ergosterol by
      15 to 30%. Subsequently, fluorescence polarization measurements also revealed
      that iron-restricted Candida cells displayed a 29 to 40% increase in membrane
      fluidity, resulting in enhanced passive diffusion of the drugs. Northern blot
      assays revealed that the ERG11 gene was considerably down regulated in iron
      deprived cells, which might account for the lowered ergosterol content. Our
      results show a close relationship between cellular iron and drug susceptibilities
      of C. albicans. Considering that multidrug resistance is a manifestation of
      multifactorial phenomena, the influence of cellular iron on the drug
      susceptibilities of Candida suggests iron as yet another novel determinant of
      multidrug resistance.

PMID- 16954315
TI  - Novel streptomycin resistance gene from Mycobacterium fortuitum.
AB  - We have isolated the aph(3")-Ic gene, encoding an aminoglycoside 3"-O
      phosphotransferase [APH(3")-Ic], from a genomic library of an environmental
      Mycobacterium fortuitum strain, selecting for streptomycin resistance. APH(3")-Ic
      phosphorylates and inactivates streptomycin. Similar genes have been described in
      Streptomyces griseus and plasmid RSF1010. It is also present in some M. fortuitum
      clinical isolates.

PMID- 16954316
TI  - Evaluation of the activities of pyrimethamine analogs against Plasmodium vivax
      and Plasmodium falciparum dihydrofolate reductase-thymidylate synthase using in
      vitro enzyme inhibition and bacterial complementation assays.
AB  - Pyrimethamine analogs were examined as potential agents against vivax malaria
      using a bacterial surrogate system carrying Plasmodium vivax dihydrofolate
      reductase-thymidylate synthase (PvDHFR-TS), in which the PvDHFR complemented
      chemically knocked out host dihydrofolate reductase. The system was initially
      tested with P. falciparum dihydrofolate reductase-thymidylate synthase and was
      found to have good correlation with the parasite-based system. The 50% inhibitory
      concentrations derived from PvDHFR-TS-dependent bacteria were correlated with
      their corresponding inhibition constants (Ki) from an enzyme inhibition assay,
      pointing to the likelihood that the potent enzyme inhibitors will also have
      potent antimalarial activities. Active compounds against both wild-type and S58R
      S117N (SP21) double-mutant P. vivax include analogs with structures which can
      avert a steric clash with the asparagine (S117N) side chain of the mutant,
      similar to those found for homologous Plasmodium falciparum mutants, raising the
      possibility that the same compounds can be developed against both types of
      antifolate-resistant malaria. This rapid and convenient drug screening system
      should be useful for development of new antifolates against P. vivax, for which a
      continuous culture system is not yet available.

PMID- 16954317
TI  - Combinations of R207910 with drugs used to treat multidrug-resistant tuberculosis
      have the potential to shorten treatment duration.
AB  - The objective of the present study was to identify the optimal R207910-containing
      regimen to administer to patients who cannot receive rifampin (RIF) and isoniazid
      (INH) because of multidrug-resistant tuberculosis (MDR-TB), concomitant use of
      antiretroviral drugs, or toxicity. Mice were infected intravenously with 5 x
      10(6) CFU of the H37Rv strain and treated five times per week with R207910 alone
      or various combinations of R207910 with the second-line drugs amikacin (AMK),
      pyrazinamide (PZA), moxifloxacin (MXF), and ethionamide (ETH). All R207910
      containing regimens were significantly more active than the non-R207910
      containing regimens after 1 month of therapy. When given for 2 months, R207910
      alone was more active than the WHO standard first-line regimen RIF-INH-PZA. When
      R207910 was combined with second-line drugs, the combinations were more active
      than the currently recommended regimen of MDR-TB AMK-ETH-MXF-PZA, and culture
      negativity of both the lungs and spleen was reached after 2 months of treatment
      in almost every case.

PMID- 16954318
TI  - Synergism between beta-lactams and glycopeptides against VanA-type methicillin
      resistant Staphylococcus aureus and heterologous expression of the vanA operon.
AB  - Vancomycin resistance of Staphylococcus aureus NY-VRSA and VRSA-5 is due to
      acquisition of a vanA operon located in a Tn1546-like element. The vanA gene
      cluster of NY-VRSA contained one copy of insertion sequences IS1251 and IS1216V
      relative to that of VRSA-5. As evidenced by the nature of the late peptidoglycan
      precursors and by quantification of d,d-peptidase activities, the vancomycin
      resistance genes were efficiently expressed in both strains. Study of the
      stability and inducibility of glycopeptide resistance suggested that low-level
      glycopeptide resistance of NY-VRSA was most probably due to plasmid instability
      combined with a long delay for resistance induction. The activity of combinations
      of vancomycin or teicoplanin with oxacillin against the four VanA-type S. aureus
      strains already reported was tested by single and double disk diffusion, E-test
      on agar alone or supplemented with antibiotics, the checkerboard technique, and
      by determining time-kill curves. A strong synergism against the four clinical
      isolates, with fractional inhibitory concentration indexes from 0.008 to 0.024,
      was reproducibly observed between the two antibiotics by all methods. These
      observations indicate that cell wall inhibitors of the beta-lactam and
      glycopeptide classes exert strong and mutual antagonistic effects on resistance
      to each other against VanA-type methicillin-resistant S. aureus.

PMID- 16954319
TI  - Anidulafungin pharmacokinetics and microbial response in neutropenic mice with
      disseminated candidiasis.
AB  - Candidemia is often fatal, especially in patients with persistent neutropenia.
      New therapies are needed. We performed 24-h pharmacodynamic studies to compare
      the efficacies of anidulafungin, fluconazole, and amphotericin B in neutropenic
      mice with disseminated candidiasis caused by one of three strains of Candida
      glabrata. Anidulafungin produced a maximal fungal kill (E(max)) of 1.4 to 1.9
      log(10) CFU/g in kidneys and was not influenced by resistance to either
      fluconazole or amphotericin B. Fluconazole produced an E(max) of 1.3 log(10)
      CFU/g in mice infected with fluconazole-susceptible C. glabrata, but the E(max)
      was 0 for mice infected with a C. glabrata strain that had a fluconazole MIC of
      >/=32 mg/liter. Amphotericin B achieved an E(max) of 4.2 log(10) CFU/g in mice
      infected with amphotericin B-susceptible C. glabrata, but the E(max) was 0 for
      mice infected with a C. glabrata strain with an amphotericin B MIC of 2 mg/liter.
      In all instances, anidulafungin's maximal microbial kill was superior to that of
      fluconazole. Next, we performed a 96-h anidulafungin pharmacokinetic
      pharmacodynamic study. Anidulafungin exhibited delayed peak concentrations in
      kidneys compared to those in serum, after which the concentrations declined, with
      a serum terminal half-life of 21.6 (+/-4.6) h. This was accompanied by a
      persistent 96-h decrease in the kidney fungal burden after treatment with a
      single anidulafungin dose of >/=8 mg/kg of body weight. This pharmacokinetic
      pharmacodynamic picture of anidulafungin persistence in tissues and the resultant
      persistent fungal decline should be exploited to improve the efficacy of
      anidulafungin therapy for candidemia.

PMID- 16954320
TI  - Derivation of an in vivo drug exposure breakpoint for flucytosine against Candida
      albicans and Impact of the MIC, growth rate, and resistance genotype on the
      antifungal effect.
AB  - Drug exposure or pharmacodynamic breakpoints refer to a magnitude of drug
      exposure which separates a population into groups with high and low probabilities
      of attaining a desired outcome. We used a pharmacodynamic model of disseminated
      candidiasis to define an in vivo drug exposure breakpoint for flucytosine (5FC)
      against Candida albicans. The results were bridged to humans by using population
      pharmacokinetics and Monte Carlo simulation. An in vivo drug exposure breakpoint
      for 5FC was apparent when serum levels were above the MIC for 45% of the dosing
      interval. The Monte Carlo simulations suggested that using a human dose of 100
      mg/kg of body weight/day in four divided doses, 5FC resistance was defined at an
      MIC of 32 mg/liter. Target attainment rates following administration of 25, 50,
      and 100 mg/kg/day were similar, suggesting that the use of a lower dose of 5FC is
      possible. Using six isolates of C. albicans with MICs ranging from 0.06 to >64
      mg/liter, we also explored the influence that the MIC, the fraction of the dosing
      interval that the serum levels of 5FC remained above the MIC (T>MIC), the 5FC
      resistance genotype, and the in vivo growth rate had on the response to 5FC. The
      MIC and T>MIC were both critical measures affecting the generation of a drug
      effect but had no bearing on the magnitude of the maximal kill induced by 5FC.
      The in vivo growth rate was a critical additional determinant of the exposure
      response relationship. There was a relationship between the 5FC resistance
      genotype and the exposure-response relationship.

PMID- 16954321
TI  - Prevalence in the United States of aac(6')-Ib-cr encoding a ciprofloxacin
      modifying enzyme.
AB  - Among 313 Enterobacteriaceae from the United States with a ciprofloxacin MIC of
      >/=0.25 microg/ml and reduced susceptibility to ceftazidime, aac(6')-Ib was
      present in 50.5% of isolates, and of these, 28% carried the cr variant
      responsible for low-level ciprofloxacin resistance. aac(6')-Ib-cr was
      geographically widespread, stable over time, most common in Escherichia coli,
      equally prevalent in ciprofloxacin-susceptible and -resistant strains, and not
      associated with qnr genes.

PMID- 16954322
TI  - DNA methylase activity as a marker for the presence of a family of phage-like
      elements conferring efflux-mediated macrolide resistance in streptococci.
AB  - Recently, two related chimeric genetic elements (Tn1207.3 and Phi10394.4) were
      shown to carry the macrolide efflux gene mef in Streptococcus pyogenes (group A
      streptococci [GAS]). The dissemination of elements belonging to the
      Tn1207.3/Phi10394.4 family in recent isolates of GAS, Streptococcus dysgalactiae
      subsp. equisimilis, Streptococcus pneumoniae, and Streptococcus agalactiae
      recovered in Portugal was surveyed. In total, 149 GAS, 18 S. pneumoniae, 4 S.
      dysgalactiae subsp. equisimilis, and 5 S. agalactiae isolates from infections,
      presenting the M phenotype of macrolide resistance and containing the mef gene,
      were screened for the presence of Tn1207.3/Phi10394.4 by PCR targeting open
      reading frames (ORFs) specific for these related elements. All the GAS isolates
      tested and one of the S. dysgalactiae subsp. equisimilis isolates carried
      Tn1207.3. However, neither of these elements was found in the isolates of the
      other streptococcal species. It was also noted that the DNAs of the isolates
      carrying Tn1207.3 were resistant to cleavage by the endonuclease SmaI. Cloning
      and expression of ORF12 of Tn1207.3 in Escherichia coli showed that it encoded a
      methyltransferase that rendered DNA refractory to cleavage by SmaI (M.Spy10394I).
      Using this characteristic as a marker for the presence of the Tn1207.3/Phi10394.4
      family, we reviewed the literature and concluded that these genetic elements are
      widely distributed among tetracycline-susceptible GAS isolates presenting the M
      phenotype from diverse geographic origins and may have played an important role
      in the dissemination of macrolide resistance in this species.

PMID- 16954323
TI  - In vitro metacestodicidal activities of genistein and other isoflavones against
      Echinococcus multilocularis and Echinococcus granulosus.
AB  - Echinococcus multilocularis and Echinococcus granulosus metacestode infections in
      humans cause alveolar echinococcosis and cystic echinococcosis, respectively, in
      which metacestode development in visceral organs often results in particular
      organ failure. Further, cystic hydatidosis in farm animals causes severe economic
      losses. Although benzimidazole derivatives such as mebendazole and albendazole
      are being used as therapeutic agents, there is often no complete recovery after
      treatment. Hence, in searching for novel treatment options, we examined the in
      vitro efficacies of a number of isoflavones against Echinococcus metacestodes and
      protoscoleces. The most prominent isoflavone, genistein, exhibits significant
      metacestodicidal activity in vitro. However, genistein binds to the estrogen
      receptor and can thus induce estrogenic effects, which is a major concern during
      long-term chemotherapy. We have therefore investigated the activities of a number
      of synthetic genistein derivatives carrying a modified estrogen receptor binding
      site. One of these, Rm6423, induced dramatic breakdown of the structural
      integrity of the metacestode germinal layer of both species within 5 to 7 days of
      in vitro treatment. Further, examination of the culture medium revealed increased
      leakage of parasite proteins into the medium during treatment, but zymography
      demonstrated a decrease in the activity of metalloproteases. Moreover, two of the
      genistein derivatives, Rm6423 and Rm6426, induced considerable damage in E.
      granulosus protoscoleces, rendering them nonviable. These findings demonstrate
      that synthetic isoflavones exhibit distinct in vitro effects on Echinococcus
      metacestodes and protoscoleces, which could potentially be exploited further for
      the development of novel chemotherapeutical tools against larval-stage
      Echinococcus infection.

PMID- 16954324
TI  - A synthetic congener modeled on a microbicidal domain of thrombin- induced
      platelet microbicidal protein 1 recapitulates staphylocidal mechanisms of the
      native molecule.
AB  - Thrombin-induced platelet microbicidal protein 1 (tPMP-1) is a staphylocidal
      peptide released by activated platelets. This peptide initiates its microbicidal
      activity by membrane permeabilization, with ensuing inhibition of intracellular
      macromolecular synthesis. RP-1 is a synthetic congener modeled on the C-terminal
      microbicidal alpha-helix of tPMP-1. This study compared the staphylocidal
      mechanisms of RP-1 with those of tPMP-1, focusing on isogenic tPMP-1-susceptible
      (ISP479C) and -resistant (ISP479R) Staphylococcus aureus strains for the
      following quantitative evaluations: staphylocidal efficacy; comparative MIC;
      membrane permeabilization (MP) and depolarization; and DNA, RNA, and protein
      synthesis. Although the proteins had similar MICs, RP-1 caused significant
      killing of ISP479C (<50% survival), correlating with extensive MP (>95%) and
      inhibition of DNA and RNA synthesis (>90%), versus substantially reduced killing
      of ISP479R (>80% survival), with less MP (55%) and less inhibition of DNA or RNA
      synthesis (70 to 80%). Interestingly, RP-1-induced protein synthesis inhibition
      was equivalent in both strains. RP-1 did not depolarize the cell membrane and
      caused a relatively short postexposure growth inhibition. These data closely
      parallel those previously reported for tPMP-1 against this strain set and
      exemplify how synthetic molecules can be engineered to reflect structure-activity
      relationships of functional domains in native host defense effector molecules.

PMID- 16954325
TI  - Analysis of the topology of Vibrio cholerae NorM and identification of amino acid
      residues involved in norfloxacin resistance.
AB  - NorM, a putative efflux pump of Vibrio cholerae, is a member of the multidrug and
      toxic compound extrusion family of transporters. We demonstrate that NorM confers
      resistance to norfloxacin, ciprofloxacin, and ethidium bromide. Inactivation of
      norM rendered V. cholerae hypersensitive towards these fluoroquinolones. Multiple
      sequence alignment of members of its family identified several regions of high
      sequence conservation. The topology of NorM was determined using beta-lactamase
      and chloramphenicol acetyltransferase fusions. The amino acid residues G(184),
      K(185), G(187), P(189), E(190), G(192), and G(195) in the periplasmic loops and
      L(381), R(382), G(383), Y(384), K(385), and D(386) in the cytoplasmic loops, as
      well as all the acidic and cysteine residues of NorM, were mutated. Mutants
      G184V, G184W, K185I, P189S, E190K, and E190A lost the norfloxacin resistance
      imparting phenotype characteristic of NorM. Mutants E124V, D155V, G187V, G187R,
      C196S, Y384H, Y384S, and Y384F exhibited partial resistance to norfloxacin.
      Mutants with replacements of G(184) or G(187) by A, K(185) by R, and E(190) by D
      retained the norfloxacin resistance phenotype of NorM. Analysis of the
      accumulation of norfloxacin in intact cells of Escherichia coli expressing NorM
      or its mutants in the presence or absence of carbonyl cyanide m
      chlorophenylhydrazone supported the results obtained through susceptibility
      testing and argued in favor of NorM-mediated efflux as the determining factor in
      norfloxacin susceptibility in the genetically manipulated strains. Taken
      together, these results suggested that E(124), D(155), G(184), K(185), G(187),
      P(189), E(190), C(196), and Y(384) are likely involved in NorM-dependent
      norfloxacin efflux. Except for D(155), C(196), and Y(384), all of these residues
      are located in periplasmic loops.

PMID- 16954326
TI  - Use of modafinil for the treatment of attention deficit/hyperactivity disorder.
AB  - OBJECTIVE: To review the evidence for the use of modafinil in the treatment of
      attention deficit/hyperactivity disorder (ADHD). DATA SOURCES: A MEDLINE search
      (January 1990-May 2006) was conducted using MeSH terms ADHD and modafinil. The
      search was limited to English-language articles on clinical trials in humans. The
      Cochrane Database was also searched. STUDY SELECTION AND DATA EXTRACTION: The
      literature search yielded 4 randomized clinical trials. DATA SYNTHESIS: The use
      of modafinil in the treatment of ADHD is associated with significant improvements
      in primary outcome measures used to assess the status of patients diagnosed with
      ADHD. Several aspects of cognitive function in ADHD patients also appear to
      improve following modafinil treatment. Modafinil shows a favorable adverse effect
      profile. Insomnia and headache were the most common adverse effects, seen in
      approximately 20% of treated individuals. However, it has not been demonstrated
      that the beneficial effects of modafinil are maintained with chronic
      administration. CONCLUSIONS: Modafinil may be a viable option for some patients
      in the treatment of ADHD, perhaps those for whom standard ADHD therapies have not
      been successful or tolerated. There remains a need for additional large, long
      term studies using flexible titration methods to optimize the dose of modafinil
      to establish safety and efficacy, as well as head-to-head comparisons between
      modafinil and both long- and short-acting stimulants to determine the role of
      modafinil in the treatment of ADHD.

PMID- 16954327
TI  - Decreased activity of clotting factor V during ALL consolidation treatment with
      mercaptopurine in a child.

PMID- 16954328
TI  - Efficacy and safety of a furosemide continuous infusion following cardiac
      surgery.
AB  - OBJECTIVE: To review the literature regarding the efficacy and safety of
      continuous intravenous infusion of loop diuretics following cardiac surgery. DATA
      SOURCES: Articles were identified through a MEDLINE search (1966-March 2006)
      using the key words furosemide, bumetanide, torsemide, ethacrynic acid, loop
      diuretics, continuous infusions, intravenous infusions, surgery, cardiac surgery,
      cardiovascular surgery, and thoracic surgery. Search results were limited to
      studies in human subjects published in English. Additional references were
      identified through review of the bibliographies of the articles cited. STUDY
      SELECTION AND DATA EXTRACTION: All clinical trials and observational reports
      identified that evaluated or described the efficacy and/or safety of a continuous
      infusion of a loop diuretic in adult or pediatric patients who had undergone
      cardiac surgery were included in this review. DATA SYNTHESIS: Loop diuretics are
      often used to promote diuresis following cardiac surgery. Studies in patients who
      have undergone cardiac surgery have demonstrated that a more consistent and
      sustained diuresis is produced by a continuous infusion of furosemide compared
      with intermittent bolus doses of furosemide. However, there does not appear to be
      a significant difference in total urine output or change in serum electrolyte
      levels when furosemide is administered as a continuous infusion compared with
      intermittent bolus doses. CONCLUSIONS: A continuous infusion of furosemide is an
      effective and safe method of diuresis in patients undergoing cardiac surgery.

PMID- 16954329
TI  - Novel in vitro system for functional assessment of oxytocin action.
AB  - One of the classical biological actions mediated by the posterior pituitary
      hormone oxytocin (OT) is contraction of the uterus at parturition. Moreover,
      premature activation of the OT system is thought to contribute to preterm labor,
      a major clinical problem in obstetrical practice. However, the molecular
      mechanisms linking activation of the OT receptor (OTR) to myometrial contractions
      are not fully understood. Here, we describe an in vitro system that should serve
      as a useful tool to study this question at a cellular level. The system consists
      of a collagen lattice contraction assay and two different human myometrial cell
      lines: a cell clone from a telomerase-immortalized human myometrial cell
      population (hTERT-C3) as well as a cell line derived from a primary culture of
      human myometrial cells (M11). Using this approach, we observed that 1 nM OT
      promoted an almost maximal effect on cell contraction in both cell lines tested.
      Furthermore, this dose-dependent, OT-induced contraction was antagonized by the
      specific OTR antagonist d(CH(2))(5)[Tyr(Me)(2),Thr(4),Tyr-NH(2)(9)]OVT as well as
      the clinically used antagonist atosiban. This cell line-based contraction assay
      enables the application of molecular tools aimed at suppressing or overexpressing
      specific genes. It is also amenable to high-throughput testing approaches.
      Therefore, this system represents a powerful and improved experimental model that
      should facilitate the study of the molecular signal transduction pathways
      involved in the uterotonic actions of OT.

PMID- 16954330
TI  - Quantification of amino acid transport through interstitial fluid: assessment of
      four-compartment modeling for muscle protein kinetics.
AB  - The purpose of this study was to assess a novel technique for quantifying in vivo
      muscle protein metabolism and phenylalanine transport in septic patients and
      normal volunteers and thereby assess the influence of sepsis on muscle protein
      kinetics. In patients resuscitated from sepsis, blood flow and edema may
      influence the extent of muscle loss. Six adult patients septic from pneumonia
      underwent a study protocol consisting of infusion of isotopic phenylalanine,
      indocyanine green dye, and sodium bromide; biopsies of skeletal muscle; and
      sampling from the femoral artery, vein, and interstitial fluid. Study results
      demonstrate a substantial net catabolism of muscle, an accelerated flux of
      phenylalanine, and an increased leg blood flow for septic patients compared with
      normal volunteers. For septic patients and normal volunteers, the rate of
      phenylalanine transport through the interstitium was rate limiting for the
      movement of phenylalanine between vasculature and muscle. Measurements
      demonstrate a concentration gradient of phenylalanine favoring the net efflux of
      amino acids from the leg in the septic patients. Despite whole body edema, the
      extracellular fluid volume within muscle of septic patients was similar to
      normal. These findings demonstrate that the extent of muscle loss in critically
      ill patients results from the net increase in the rate of muscle protein
      breakdown, which subsequently drives amino acids through the interstitial
      compartment down their concentration gradient. Therefore, any effective therapy
      to correct illness-induced muscle catabolism should be directed at altering the
      rates of breakdown and synthesis of muscle protein and are not likely related to
      tissue edema.

PMID- 16954331
TI  - Contribution of nitric oxide to cutaneous microvascular dilation in individuals
      with type 2 diabetes mellitus.
AB  - Microvascular pathophysiology associated with type 2 diabetes mellitus (T2DM)
      contributes to several aspects of the morbidity associated with the disease. We
      quantified the contribution of nitric oxide (NO) to the cutaneous vasodilator
      response to nonpainful local warming in subjects with T2DM (average duration of
      diabetes mellitus 7 +/- 1 yr) and in age-matched control subjects. We measured
      skin blood flow in conjunction with intradermal microdialysis of N(G)-nitro-l
      arginine methyl ester (l-NAME; NO synthase inhibitor) or vehicle during 35 min of
      local warming to 42 degrees C. Microdialysis of sodium nitroprusside (SNP) was
      used for assessment of maximum cutaneous vascular conductance (CVC). Resting CVC
      was higher in T2DM subjects at vehicle sites (T2DM: 19 +/- 2 vs. control: 11 +/-
      3%maxCVC; P < 0.05); this difference was abolished by l-NAME (T2DM: 10 +/- 1 vs.
      control: 8 +/- 1%maxCVC; P > 0.05). The relative contribution of NO to the
      vasodilator response to local warming was not different between groups (T2DM: 46
      +/- 4 vs. control: 44 +/- 6%maxCVC; P > 0.05). However, absolute CVC during local
      warming was approximately 25% lower in T2DM subjects (T2DM: 1.79 +/- 0.15
      AU/mmHg; controls: 2.42 +/- 0.20 AU/mmHg; P < 0.01), and absolute CVC during SNP
      was approximately 20% lower (T2DM: 1.91 +/- 0.12 vs. control: 2.38 +/- 0.13
      AU/mmHg; P < 0.01). We conclude that the relative contribution of NO to
      vasodilation during local warming is similar between subjects with T2DM and
      control subjects, although T2DM was associated with a lower absolute maximum
      vasodilation.

PMID- 16954332
TI  - Adipose tissue in offspring of Lepr(db/+) mice: early-life environment vs.
      genotype.
AB  - Gravidas with obesity and diabetes ("diabesity") may transmit this syndrome to
      their children through genetic and nongenetic mechanisms. Here, we used the
      Lepr(db/+) diabese mouse to examine the magnitude of these transmission modes,
      focusing on adipose tissue (AT). We compared the following six groups: wild-type
      (+/+) offspring from +/+ or db/+ dams (different early life environment) and db/+
      offspring from db/+ dams, fed a standard or high-fat diet. Weight gain (0-8 wk)
      was higher in +/+ offspring from db/+ vs. +/+ mothers, and even higher in db/+
      vs. +/+ offspring from db/+ mothers. In addition, we observed a stepwise increase
      in AT and adipocyte size in +/+ from +/+ mice, +/+ from db/+ mice, and db/+ mice
      at 8 wk. Differences in weight and adiposity between +/+ offspring from db/+ vs.
      +/+ dams were more pronounced in males than in females. Leptin and apelin mRNA
      levels in white and brown AT were higher in +/+ offspring from db/+ vs. +/+ dams;
      however, leptin, apelin, and tumor necrosis factor-alpha expression were boosted
      more robustly in db/+ offspring. The high-fat diet amplified AT differences
      between db/+ vs. +/+ offspring from db/+ dams, but not between +/+ offspring from
      db/+ vs. +/+ dams. Moreover, db/+ but not +/+ offspring from db/+ mothers were
      insulin-resistant and hyperinsulinemic after a glucose challenge. In conclusion,
      the genetic transmission of the diabesity phenotype clearly prevailed, but the
      early-life diabesity environment had discernible effects on postnatal weight gain
      as well as on adipocyte size and adipokine expression at a postpubertal age.

PMID- 16954333
TI  - Epithelial lining fluid free IGF-I-to-PAPP-A ratio is associated with
      bronchopulmonary dysplasia in preterm infants.
AB  - Preterm newborns developing retinopathy of prematurity (ROP) and bronchopulmonary
      dysplasia (BPD) show persistently low levels of insulin-like growth factor-I (IGF
      I) in sera. They also present higher free IGF-I concentrations in epithelial
      lining fluids (ELFs) and lung tissues. Pregnancy-associated plasma protein-A
      (PAPP-A) is a metalloproteinase that dissociates three binding proteins from the
      active form of IGF-I, namely free IGF-I. The present study analyzes the ELF
      concentrations of free IGF-I, PAPP-A, and their ratios in preterm newborns
      developing or not BPD, defined as O(2) dependence at 36 wk postmenstrual age.
      Bronchoalveolar lavage fluids of 41 infants (34 without and 7 with BPD) were
      analyzed on the 2nd and 4th day after birth. Infants developing BPD showed
      increased ELF free IGF-I and decreased PAPP-A concentrations on both days 2 and 4
      compared with newborns without BPD. A nonsignificant trend between these 2 days
      was observed for free IGF-I (increasing) and PAPP-A (decreasing). On the same
      days, the free IGF-I-to-PAPP-A ratio was always significantly higher in patients
      developing BPD. These differences were more significant than those of IGF-I or
      PAPP-A when individually evaluated. A multivariate analysis confirmed the
      significance for free IGF-I on day 4, whereas the ratio was confirmed on both
      days 2 and 4. The same ratio was significantly correlated with some indexes of
      disease severity, such as hours of oxygen administration, days of
      hospitalization, and ROP severity scores. Finally, the ratio between ELF free IGF
      I and PAPP-A appears to be a useful marker for lung injury of premature newborns.

PMID- 16954334
TI  - Role of AMPKalpha2 in basal, training-, and AICAR-induced GLUT4, hexokinase II,
      and mitochondrial protein expression in mouse muscle.
AB  - We investigated the role of AMPKalpha2in basal, exercise training-, and AICAR
      induced protein expression of GLUT4, hexokinase II (HKII), mitochondrial markers,
      and AMPK subunits. This was conducted in red (RG) and white gastrocnemius (WG)
      muscle from wild-type (WT) and alpha2-knockout (KO) mice after 28 days of
      activity wheel running or daily AICAR injection. Additional experiments were
      conducted to measure acute activation of AMPK by exercise and AICAR. At basal,
      mitochondrial markers were reduced by approximately 20% in alpha2-KO muscles
      compared with WT. In both muscle types, AMPKalpha2 activity was increased in
      response to both stimuli, whereas AMPKalpha1 activity was increased only in
      response to exercise. Furthermore, AMPK signaling was estimated to be 60-70%
      lower in alpha2-KO compared with WT muscles. In WG, AICAR treatment increased
      HKII, GLUT4, cytochrome c, COX-1, and CS, and the alpha2-KO abolished the AICAR
      induced increases, whereas no AICAR responses were observed in RG. Exercise
      training increased GLUT4, HKII, COX-1, CS, and HAD protein in WG, but the alpha2
      KO did not affect training-induced increases. Furthermore, AMPKalpha1, -alpha2, 
      beta1, -beta2, and -gamma3 subunits were reduced in RG, but not in WG, by 30-60%
      in response to exercise training. In conclusion, the alpha2-KO was associated
      with an approximately 20% reduction in mitochondrial markers in both muscle types
      and abolished AICAR-induced increases in protein expression in WG. However, the
      alpha2-KO did not reduce training-induced increases in HKII, GLUT4, COX-1, HAD,
      or CS protein in WG, suggesting that AMPKalpha2 may not be essential for
      metabolic adaptations of skeletal muscles to exercise training.

PMID- 16954335
TI  - Expression of mitochondrial biogenesis-signaling factors in brown adipocytes is
      influenced specifically by 17beta-estradiol, testosterone, and progesterone.
AB  - Control of mitochondrial biogenesis in brown adipose tissue (BAT), as part of the
      thermogenesis program, is a complex process that requires the integration of
      multiple transcription factors to orchestrate mitochondrial and nuclear gene
      expression. Despite the knowledge of the role of sex hormones on BAT physiology,
      little is known about the effect of these hormones on the mitochondrial biogenic
      program. The aim of this study was to determine the effect of testosterone,
      17beta-estradiol, and progesterone on the expression of nuclear factors involved
      in the control of mitochondrial biogenesis and thermogenic function such as
      ppargamma, pgc1alpha, nrf1, gabpa, and tfam, and also an inhibitor of PI3K-Akt
      pathway, recently found to be involved in the control of mitochondrial
      recruitment (pten). For this purpose, an in vitro assay using cell-cultured brown
      adipocytes was used to address the role of steroid hormones, progesterone,
      testosterone, and 17beta-estradiol on the mRNA expression of these factors by
      real-time PCR. Thus 17beta-estradiol seemed to exert a dual effect, activating
      the PI3K-Akt pathway by inhibiting pten mRNA expression and also inhibiting nrf1
      and tfam mRNA expression. Progesterone seemed to positively stimulate
      mitochondriogenesis and BAT differentiation by increasing the mRNA expression of
      the gabpa-tfam axis and ppargamma, respectively, but also exerted a negative
      output by increasing pten mRNA levels. Finally, testosterone inhibited the
      transcription of pgc1alpha, the master factor involved in UCP1 expression and
      mitochondrial biogenesis. In conclusion, our results support the idea that sex
      hormones have direct effects on different mediators of the mitochondriogenesis
      program.

PMID- 16954336
TI  - GLP-2 rapidly activates divergent intracellular signaling pathways involved in
      intestinal cell survival and proliferation in neonatal piglets.
AB  - We previously demonstrated the dose-dependent glucagon-like peptide (GLP)-2
      activation of intracellular signals associated with increased epithelial cell
      survival and proliferation in the neonatal intestine. Our current aim was to
      quantify the acute, temporal GLP-2 activation of these key intracellular signals
      and relate this to changes in epithelial cell survival and proliferation in the
      neonatal intestine. We studied 29 total parenteral nutrition-fed neonatal piglets
      infused intravenously with either saline (control) or human GLP-2 (420
      micromol.kg(-1).h(-1)) for 1, 4, or 48 h. GLP-2 infusion increased small
      intestinal weight, DNA and protein content, and villus height at 48 h, but not at
      1 or 4 h. Intestinal crypt and villus apoptosis decreased and crypt cell
      proliferation and protein synthesis increased linearly with duration of GLP-2
      infusion, but were statistically different from controls only after 48 h. Before
      the morphological and cellular kinetic changes, GLP-2 rapidly activated putative
      GLP-2 receptor downstream signals within 1-4 h, including phosphorylation of
      protein kinase A, protein kinase B, extracellular signal-regulated kinase 1/2,
      and the transcription factors cAMP response element-binding protein and c-Fos.
      GLP-2 rapidly suppressed caspase-3 activation and upregulated Bcl-2 abundance
      within 1 h, whereas there was an increase in apoptosis inhibitors X-linked
      inhibitor of apoptosis at 1 h and cellular inhibitor of apoptosis-2 at 4 and 48
      h. We also show that the increased c-Fos and reduced active caspase-3
      immunostaining after GLP-2 infusion was localized in epithelial cells. We
      conclude that GLP-2-induced activation of intracellular signals involved in both
      cell survival and proliferation occurs rapidly and precedes the trophic cellular
      kinetic effects that occur later in intestinal epithelial cells.

PMID- 16954337
TI  - Increased postprandial responses of GLP-1 and GIP in patients with chronic
      pancreatitis and steatorrhea following pancreatic enzyme substitution.
AB  - We aimed to investigate how assimilation of nutrients affects the postprandial
      responses of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic
      polypeptide (GIP) and to evaluate the effect of pancreatic enzyme substitution
      (PES) on insulin secretion in patients with chronic pancreatitis (CP) and
      pancreatic exocrine insufficiency (PEI). Eight male patients with CP and PEI were
      studied. Blood was sampled frequently on two separate days after ingestion of a
      liquid meal with and without PES, respectively. Eight healthy male subjects
      served as a control group. beta-Cell responsiveness was estimated as changes in
      insulin secretion rates in response to changes in postprandial plasma glucose
      (PG). There was no difference in the PG incremental area under curve (AUC) for
      patients with and without PES [406 +/- 100 vs. 425 +/- 80 mM.4 h (mean +/- SE), P
      = 0.8]. The response of total GLP-1 was higher after PES (AUC: 7.8 +/- 1.2 vs.
      5.3 +/- 0.6 nM.4 h, P = 0.01), as was the response of total GIP (AUC: 32.7 +/-
      7.5 vs. 21.1 +/- 8.3 nM.4 h, P = 0.01). Concurrently, both plasma insulin, plasma
      C-peptide, and total insulin secretion increased after PES (AUC: 17.7 +/- 4.2 vs.
      13.6 +/- 2.9 nM.4 h, P = 0.02; 237 +/- 31.4 vs. 200 +/- 27.4 nM.4 h, P = 0.005;
      and 595 +/- 82 vs. 497 +/- 80 pmol.kg(-1).4 h, P = 0.01, respectively). beta-Cell
      responsiveness to glucose was not significantly different on the two study days
      for patients with CP. These results suggest that the secretion of GLP-1 and GIP
      is under influence of the digestion and absorption of nutrients in the small
      intestine and that PES increases insulin secretion.

PMID- 16954338
TI  - Population approaches to estimate minimal model indexes of insulin sensitivity
      and glucose effectiveness using full and reduced sampling schedules.
AB  - The intravenous glucose tolerance test (IVGTT) interpreted with the minimal model
      provides individual indexes of insulin sensitivity (S(I)) and glucose
      effectiveness (S(G)). In population studies, the traditional approach, the
      standard two-stage (STS) method, fails to account for uncertainty in individual
      estimates, resulting in an overestimation of between-subject variability.
      Furthermore, in the presence of reduced sampling and/or insulin resistance,
      individual estimates may be unobtainable, biasing population information.
      Therefore, we investigated the use of two population approaches, the iterative
      two-stage (ITS) method and nonlinear mixed-effects modeling (NM), in a population
      (n = 235) of insulin-sensitive and insulin-resistant subjects under full (FSS, 33
      samples) and reduced [RSS(240-min), 13 samples and RSS(180-min), 12 samples]
      IVGTT sampling schedules. All three population methods gave similar results with
      the FSS. Using RSS(240), the three methods gave similar results for S(I), but
      S(G) population means were overestimated. With RSS(180), S(I) and S(G) population
      means were higher for all three methods compared with their FSS counterparts. NM
      estimated similar between-subject variability (19% S(G), 53% S(I)) with RSS(180),
      whereas ITS showed regression to the mean for S(G) (0.01% S(G), 56% S(I)) and STS
      provided larger population variability in S(I) (29% S(G), 91% S(I)). NM provided
      individual estimates for all subjects, whereas the two-stage methods failed in 16
      18% of the subjects using RSS(180) and 6-14% using RSS(240). We conclude that
      population approaches, specifically NM, are useful in studies with a sparsely
      sampled IVGTT ( approximately 12 samples) of short duration ( approximately 3 h)
      and when individual parameter estimates in all subjects are desired.

PMID- 16954339
TI  - TRPV4 as a flow sensor in flow-dependent K+ secretion from the cortical
      collecting duct.
AB  - The transient receptor vanilloid-4 (TRPV4) is a mechanosensitive, swell-activated
      cation channel that is abundant in the renal distal tubules. Immunolocalization
      studies, however, present conflicting data as to whether TRPV4 is expressed along
      the apical and/or basolateral membranes. To disclose the role of TRPV4 in flow
      dependent K(+) secretion in distal tubules in vivo, urinary K(+) excretion and
      net transports of K(+) and Na(+) in the cortical collecting duct (CCD) were
      measured with an in vitro microperfusion technique in TRPV4(+/+) and TRPV4(-/-)
      mice. Both net K(+) secretion and Na(+) reabsorption were flow dependently
      increased in the CCDs isolated from TRPV4(+/+)mice, which were significantly
      enhanced by a luminal application of 50 microM 4alpha-phorbol-12,13-didecanoate
      (4alphaPDD), an agonist of TRPV4. No flow dependence of net K(+) and Na(+)
      transports or effects of 4alphaPDD on CCDs were observed in TRPV4(-/-) mice. A
      basolateral application of 4alphaPDD had little effect on these ion transports in
      the TRPV4(+/+) CCDs, while the luminal application did. Urinary K(+) excretion
      was significantly smaller in TRPV4(-/-) than in TRPV4(+/+) mice when urine
      production was stimulated by a venous application of furosemide. These
      observations suggested an essential role of the TRPV4 channels in the luminal or
      basolateral membrane as flow sensors in the mechanism underlying the flow
      dependent K(+) secretion in mouse CCDs.

PMID- 16954341
TI  - Soluble betaglycan reduces renal damage progression in db/db mice.
AB  - Transforming growth factor-beta (TGF-beta) is a key mediator in the pathogenesis
      of renal diseases. Betaglycan, also known as the type III TGF-beta receptor,
      regulates TGF-beta action by modulating its access to the type I and II
      receptors. Betaglycan potentiates TGF-beta; however, soluble betaglycan, which is
      produced by the shedding of the membrane-bound receptor, is a potent antagonist
      of TGF-beta. In the present work, we have used a recombinant form of soluble
      betaglycan (SBG) to prevent renal damage in genetically obese and diabetic db/db
      mice. Eight-wk-old db/db or nondiabetic (db/m) mice were injected
      intraperitoneally with 50 mug of SBG or vehicle alone three times a wk for 8 wk.
      The db/db mice that received vehicle presented albuminuria and increased serum
      creatinine, as well as glomerular mesangial matrix expansion. The db/db mice
      treated with SBG exhibited a reduction in serum creatinine, albuminuria, and
      structural renal damage. These effects were associated with lower kidney levels
      of mRNAs encoding TGF-beta1, TGF-beta2, TGF-beta3, collagen IV, collagen I,
      fibronectin, and serum glucocorticoid kinase as well as a reduction in the
      immunostaining of collagen IV and fibronectin. Our data indicate that SBG is a
      renoprotective agent that neutralized TGF-beta actions in this model of
      nephropathy. Because SBG has a high affinity for all TGF-beta isoforms, in
      particular TGF-beta2, it is found naturally in serum and tissues and its shedding
      may be regulated. We believe that SBG shall prove convenient for long-term
      treatment of kidney diseases and other pathologies in which TGF-beta plays a
      pathophysiological role.

PMID- 16954340
TI  - Low plasma renin and reduced renin secretory responses to acute stimuli in
      conscious COX-2-deficient mice.
AB  - In the current experiments, we determined the response of plasma renin
      concentration (PRC) to acute intraperitoneal administration of furosemide (40
      mg/kg), hydralazine (2 mg/kg), isoproterenol (10 mg/kg), candesartan (50 microg),
      or quinaprilate (50 microg) in conscious wild-type (WT) and cyclooxygenase (COX)
      2-/- mice on three different genetic backgrounds (mixed, C57BL/6, 129J). PRC was
      measured in plasma obtained by tail vein puncture. Basal PRC was significantly
      lower in COX-2-/- than WT mice independent of genetic background (51, 10, and 17%
      of WT in mixed, 129J, and C57BL/6). All five acute interventions caused
      significant increases of PRC in both COX-2+/+ and -/- mice, but the response was
      consistently less in COX-2-deficient mice (e.g., DeltaPRC in ng ANG I x ml(-1) x
      h(-1) caused by furosemide, isoproterenol, hydralazine, quinaprilate, or
      candesartan 4,699 +/- 544, 3,534 +/- 957, 2,522 +/- 369, 9,453 +/- 1,705, 66,455
      +/- 21,938 in 129J WT, and 201 +/- 78, 869 +/- 275, 140 +/- 71, 902 +/- 304,
      2,660 +/- 954 in 129J COX-2-/-). A low-NaCl diet and enalapril for 1 wk caused a
      14-fold elevation of PRC in COX-2-/- mice and was associated with a greatly
      increased PRC response to acute furosemide (DeltaPRC 201 +/- 78 before and 15,984
      +/- 2,397 after low Na/enalapril). As measured by radiotelemetry, blood pressure
      and heart rate responses to furosemide, hydralazine, isoproterenol, candesartan,
      or quinaprilate were not different between COX-2 genotypes. In conclusion,
      chronic absence of COX-2 reduces renin expression, release, and PRC and is
      associated with a reduced ability to alter PRC during acute stimulation
      regardless of the nature of the stimulus. COX-2 activity does not appear to be a
      mandatory and specific requirement for furosemide-stimulated renin secretion.

PMID- 16954342
TI  - Tissue-specific regulation of ubiquitin (UbC) transcription by glucocorticoids:
      in vivo and in vitro analyses.
AB  - In uremia, muscle wasting involves increased glucocorticoid production and
      activation of the ubiquitin-proteasome proteolytic pathway, including increased
      expression of ubiquitin. Previously, we reported that glucocorticoids stimulate
      ubiquitin transcription by a mechanism involving Sp1 in L6 muscle cells
      (Marinovic AC, Zheng B, Mitch WE, Price SR. J Biol Chem 277: 16673-16681, 2002).
      This finding was surprising because Sp1 is a general transcriptional activator.
      To better understand the mechanism of glucocorticoid-induced ubiquitin (UbC) gene
      transcription, we examined whether this response occurs in many organs or
      uniquely in skeletal muscle. Glucocorticoid-responsive cells of different organs
      were transfected with a human UbC promoter-luciferase reporter plasmid;
      dexamethasone stimulated UbC reporter activity 220% (P < 0.05) in L6 skeletal
      muscle cells but not in HepG2 hepatocytes, NRK kidney cells, CaCo-2 colon cells,
      or H9c2 cardiomyocytes. Transactivation of the Sp1-responsive SV40 viral promoter
      was also increased in muscle but not in other nonmuscle cells. The muscle
      specific nature of the UbC response was confirmed in vivo in rats with insulin
      deficiency, a condition associated with high glucocorticoid production: UbC mRNA
      was elevated in skeletal muscle but not in liver, kidney, intestine, or heart.
      Electrophoretic mobility shift assays and in vivo genomic footprinting
      demonstrated that insulin deficiency increased Sp1 binding to GC-rich elements in
      the UbC promoter. Thus glucocorticoids increase UbC transcription by a mechanism
      involving Sp1 that is unique to muscle.

PMID- 16954343
TI  - Glucocorticoids have a role in renal cortical expression of the SNAT3 glutamine
      transporter during chronic metabolic acidosis.
AB  - Glucocorticoids are involved in many aspects of regulation of acid-base
      homeostasis, including the stimulation of renal ammoniagenesis during chronic
      metabolic acidosis. Plasma glutamine is the principal substrate for
      ammoniagenesis under these conditions. Expression of the System N glutamine
      transporter SNAT3 is increased in the renal proximal tubules during acidosis. In
      vivo studies in rats using 1) sham and adrenalectomized rats, 2) the
      glucocorticoid receptor antagonist RU486, and 3) dexamethasone treatment
      demonstrated involvement of glucocorticoids in regulation of SNAT3 expression.
      Adrenalectomy attenuated the acidosis-induced increase in renal cortical SNAT3
      mRNA approximately 40%, and treatment with dexamethasone (1 mg x kg(-1) x day(-1)
      sc) partially reversed this effect. RU486 also blunted the acidosis-induced
      increase in SNAT3 expression approximately 50%. Chronic dexamethasone treatment
      (0.1 mg x kg(-1) x day(-1) sc, 6 days) of normal rats slightly increased SNAT3
      expression. In all cases, renal glutamine arteriovenous difference mirrored SNAT3
      expression and activity in the proximal tubules, suggesting that SNAT3 regulates
      glutamine uptake during acidosis. These studies indicate that glucocorticoids
      regulate acid-base homeostasis during metabolic acidosis in part by regulating
      expression of the System N transporter SNAT3.

PMID- 16954344
TI  - Renal prostaglandin E2 receptor (EP) expression profile is altered in
      streptozotocin and B6-Ins2Akita type I diabetic mice.
AB  - The homeostatic function of prostaglandin E(2) (PGE(2)) is dependent on a balance
      of EP receptor-mediated events. A disruption in this balance may contribute to
      the progression of renal injury. Although PGE(2) excretion is elevated in
      diabetes, the expression of specific EP receptor subtypes has not been studied in
      the diabetic kidney. Therefore, the purpose of this study was to characterize the
      expression profile of four EP receptor subtypes (EP(1-4)) in 16-wk streptozotocin
      (STZ) and B6-Ins2(Akita) type I diabetic mice. In diabetic mice, the ratio of
      kidney weight to body weight was increased twofold compared with controls, blood
      glucose was elevated, but urine albumin was only increased in B6-Ins2(Akita)
      mice. The excretion of PGE(2) and its metabolite was augmented two- to fourfold
      as determined by enzyme immunoassay. Accordingly, renal cyclooxygenases were also
      increased in diabetic mice, with isoform-specific and regional differences in
      each model. Finally, there was altered EP(1-4) receptor expression in diabetic
      kidneys, with significant differences between STZ and B6-Ins2(Akita) mice (fold
      control). In STZ mice, cortical EP(1) increased by 1.6, EP(3) increased by 2.3,
      and EP(4) decreased by 0.63; yet in B6-Ins2(Akita) mice, cortical EP(1) increased
      by 2.4, but there was a general decrease in the remaining subtypes. Similarly, in
      the STZ medulla EP(3) increased by 3.6, but both EP(1) and EP(3) increased by 5.5
      and 1.95, respectively, in B6-Ins2(Akita) mice. Therefore, knowing the pattern of
      change in relative EP receptor expression in the kidney could be useful in
      identifying specific EP targets for the prevention of various components of
      diabetic kidney disease.

PMID- 16954345
TI  - Model of albumin reabsorption in the proximal tubule.
AB  - Normally, the small amount of albumin which passes through the glomerular
      capillary wall is almost completely reabsorbed in the proximal tubule, via an
      endocytic mechanism, but the reabsorptive process can be overwhelmed if the
      filtered load of albumin is too large. To examine the factors that control the
      fractional reabsorption of albumin (f), we developed a mathematical model which
      assumes saturable endocytosis kinetics with a maximum reabsorptive capacity,
      V(max), and which includes the effects of flow and diffusion in the lumen.
      Limitations in albumin transport from the bulk tubule fluid to the endocytic
      sites at the bases of the microvilli had only a modest (8%) effect on the value
      of V(max) needed to fit micropuncture data on tubule albumin concentrations in
      rats. For moderate changes in filtered load, there was much greater sensitivity
      of f to SNGFR than to the albumin concentration of the filtrate (C(0)). A 50%
      increase in SNGFR was predicted to cause four- to fivefold increases in albumin
      excretion in rats or humans. For large increases in C(0), as might result from
      defects in glomerular sieving, there was a threshold at which the reabsorptive
      process became saturated and f fell sharply. That threshold corresponded to
      sieving coefficients of 10(-3) to 10(-2), the higher values occurring at reduced
      SNGFR. The predictions of the present model contrast with those of one proposed
      recently by Smithies (32), which does not include the effects of tubule flow
      rate.

PMID- 16954346
TI  - Tubulin tyrosination is a major factor affecting the recruitment of CAP-Gly
      proteins at microtubule plus ends.
AB  - Tubulin-tyrosine ligase (TTL), the enzyme that catalyzes the addition of a C
      terminal tyrosine residue to alpha-tubulin in the tubulin tyrosination cycle, is
      involved in tumor progression and has a vital role in neuronal organization. We
      show that in mammalian fibroblasts, cytoplasmic linker protein (CLIP) 170 and
      other microtubule plus-end tracking proteins comprising a cytoskeleton-associated
      protein glycine-rich (CAP-Gly) microtubule binding domain such as CLIP-115 and
      p150 Glued, localize to the ends of tyrosinated microtubules but not to the ends
      of detyrosinated microtubules. In vitro, the head domains of CLIP-170 and of p150
      Glued bind more efficiently to tyrosinated microtubules than to detyrosinated
      polymers. In TTL-null fibroblasts, tubulin detyrosination and CAP-Gly protein
      mislocalization correlate with defects in both spindle positioning during mitosis
      and cell morphology during interphase. These results indicate that tubulin
      tyrosination regulates microtubule interactions with CAP-Gly microtubule plus-end
      tracking proteins and provide explanations for the involvement of TTL in tumor
      progression and in neuronal organization.

PMID- 16954347
TI  - Cell cycle regulators control centrosome elimination during oogenesis in
      Caenorhabditis elegans.
AB  - In many animals, the bipolar spindle of the first zygotic division is established
      after the contribution of centrioles by the sperm at fertilization. To avoid the
      formation of a multipolar spindle in the zygote, centrosomes are eliminated
      during oogenesis in most organisms, although the mechanism of this selective
      elimination is poorly understood. We show that cki-2, a Caenorhabditis elegans
      cyclin-dependent kinase (Cdk) inhibitor, is required for their appropriate
      elimination during oogenesis. In the absence of cki-2, embryos have supernumerary
      centrosomes and form multipolar spindles that result in severe aneuploidy after
      anaphase of the first division. Moreover, we demonstrate that this defect can be
      suppressed by reducing cyclin E or Cdk2 levels. This implies that the proper
      regulation of a cyclin E-Cdk complex by cki-2 is required for the elimination of
      the centrosome that occurs before or during oogenesis to ensure the assembly of a
      bipolar spindle in the C. elegans zygote.

PMID- 16954348
TI  - Genetic analysis of beta1 integrin "activation motifs" in mice.
AB  - Akey feature of integrins is their ability to regulate the affinity for ligands,
      a process termed integrin activation. The final step in integrin activation is
      talin binding to the NPXY motif of the integrin beta cytoplasmic domains. Talin
      binding disrupts the salt bridge between the alpha/beta tails, leading to tail
      separation and integrin activation. We analyzed mice in which we mutated the
      tyrosines of the beta1 tail and the membrane-proximal aspartic acid required for
      the salt bridge. Tyrosine-to-alanine substitutions abolished beta1 integrin
      functions and led to a beta1 integrin-null phenotype in vivo. Surprisingly,
      neither the substitution of the tyrosines with phenylalanine nor the aspartic
      acid with alanine resulted in an obvious defect. These data suggest that the NPXY
      motifs of the beta1 integrin tail are essential for beta1 integrin function,
      whereas tyrosine phosphorylation and the membrane-proximal salt bridge between
      alpha and beta1 tails have no apparent function under physiological conditions in
      vivo.

PMID- 16954349
TI  - Three-dimensional reconstruction of the membrane skeleton at the plasma membrane
      interface by electron tomography.
AB  - Three-dimensional images of the undercoat structure on the cytoplasmic surface of
      the upper cell membrane of normal rat kidney fibroblast (NRK) cells and fetal rat
      skin keratinocytes were reconstructed by electron tomography, with 0.85-nm-thick
      consecutive sections made approximately 100 nm from the cytoplasmic surface using
      rapidly frozen, deeply etched, platinum-replicated plasma membranes. The membrane
      skeleton (MSK) primarily consists of actin filaments and associated proteins. The
      MSK covers the entire cytoplasmic surface and is closely linked to clathrin
      coated pits and caveolae. The actin filaments that are closely apposed to the
      cytoplasmic surface of the plasma membrane (within 10.2 nm) are likely to form
      the boundaries of the membrane compartments responsible for the temporary
      confinement of membrane molecules, thus partitioning the plasma membrane with
      regard to their lateral diffusion. The distribution of the MSK mesh size as
      determined by electron tomography and that of the compartment size as determined
      from high speed single-particle tracking of phospholipid diffusion agree well in
      both cell types, supporting the MSK fence and MSK-anchored protein picket models.

PMID- 16954351
TI  - Unpleasant surprises: how the Introduction has wandered into the Discussion.

PMID- 16954350
TI  - Luminal particles within cellular microtubules.
AB  - The regulation of microtubule dynamics is attributed to microtubule-associated
      proteins that bind to the microtubule outer surface, but little is known about
      cellular components that may associate with the internal side of microtubules. We
      used cryoelectron tomography to investigate in a quantitative manner the three
      dimensional structure of microtubules in intact mammalian cells. We show that the
      lumen of microtubules in this native state is filled with discrete, globular
      particles with a diameter of 7 nm and spacings between 8 and 20 nm in neuronal
      cells. Cross-sectional views of microtubules confirm the presence of luminal
      material in vitreous sections of brain tissue. Most of the luminal particles had
      connections to the microtubule wall, as revealed in tomograms. A higher
      accumulation of particles was seen near the retracting plus ends of microtubules.
      The luminal particles were abundant in neurons, but were also observed in other
      cells, such as astrocytes and stem cells.

PMID- 16954352
TI  - Systematic review: smoking cessation intervention strategies for adults and
      adults in special populations.
AB  - BACKGROUND: While smoking cessation interventions have been shown to work,
      questions remain about how to increase their efficacy. PURPOSE: To examine
      strategies for effective tobacco treatment in adults and special populations.
      DATA SOURCES: MEDLINE, Cumulative Index to Nursing and Applied Health (CINAHL),
      Cochrane Library, Cochrane Clinical Trials Register, Psychological Abstracts, and
      Sociological Abstracts (1 January 1980 to 10 June 2005). STUDY SELECTION:
      Systematic reviews; randomized, controlled trials; and observational studies.
      DATA EXTRACTION: Two reviewers independently abstracted data on study design,
      population, sample size, treatment, outcomes, and quality. DATA SYNTHESIS:
      Findings from systematic reviews were summarized and compared with findings from
      original research published beyond date ranges included in the reviews. Strength
      of evidence was used to assess the body of evidence. Our review included studies
      evaluating the efficacy of cessation strategies, such as self-help, counseling,
      single pharmaceutical agents, combined pharmacotherapies, and pharmacotherapies
      combined with psychological counseling. Research findings consistent with
      previous reviews show that self-help strategies alone are ineffective, but
      counseling and pharmacotherapy used either alone or in combination can improve
      rates of success with quit attempts. Two studies of self-help materials reported
      discrepancies across effects. Five studies provided mixed results for counseling
      interventions. Fourteen studies provided sufficient evidence of the efficacy of
      single pharmacotherapy, combined pharmacotherapy, and psychological interventions
      either with or without pharmacotherapy. Few studies focused on ways to reach or
      treat special populations. Three studies with hospitalized patients had findings
      consistent with a previous review showing no strong evidence that clinical
      diagnosis affected the likelihood of quitting. New evidence was insufficient to
      address the effectiveness of interventions for persons with coexisting
      psychiatric conditions and substance abuse problems. LIMITATIONS: Previous
      systematic reviews variably cover the range of issues we addressed. More recent
      studies do not fill all gaps, especially those for persons with coexisting
      disease. CONCLUSIONS: Although self-help strategies alone marginally affect quit
      rates, individual and combined pharmacotherapies and counseling either alone or
      in combination can significantly increase cessation. Using effective smoking
      treatments is strongly encouraged for all populations, especially those with high
      and heavy rates of smoking, such as psychiatric and substance abuse populations.

PMID- 16954353
TI  - National Institutes of Health State-of-the-Science conference statement: tobacco
      use: prevention, cessation, and control.

PMID- 16954354
TI  - Summaries for patients. Cost-effectiveness of a vaccine to prevent herpes zoster
      (shingles) in older adults.

PMID- 16954355
TI  - Summaries for patients. Meal size explains errors in estimating how many calories
      are in a meal.

PMID- 16954356
TI  - Summaries for patients. The effect of virgin and refined olive oils on heart
      disease risk factors.

PMID- 16954357
TI  - Cost-effectiveness of a vaccine to prevent herpes zoster and postherpetic
      neuralgia in older adults.
AB  - BACKGROUND: The Shingles Prevention Study showed that a varicella-zoster virus
      (VZV) vaccine administered to adults 60 years of age or older reduced the
      incidence of herpes zoster from 11.12 to 5.42 cases per 1000 person-years. Median
      follow-up was 3.1 years, and relative risk reduction was 51.3% (95% CI, 44.2% to
      57.6%). OBJECTIVE: To assess the extent to which clinical and cost variables
      influence the cost-effectiveness of VZV vaccination for preventing herpes zoster
      in immunocompetent older adults. DESIGN: Decision theoretical model. DATA
      SOURCES: English-language data published to March 2006 identified from MEDLINE on
      herpes zoster rates, vaccine effectiveness, quality of life, medical resource
      use, and unit costs. TARGET POPULATION: Immunocompetent adults 60 years of age or
      older with a history of VZV infection. TIME HORIZON: Lifetime. PERSPECTIVE: U.S.
      societal. INTERVENTIONS: Varicella-zoster virus vaccination versus no
      vaccination. OUTCOME MEASURES: Incremental quality-adjusted survival and cost per
      quality-adjusted life-year (QALY) gained. RESULTS OF BASE-CASE ANALYSIS: By
      reducing incidence and severity of herpes zoster, vaccination can increase
      quality-adjusted survival by 0.6 day compared with no vaccination. One scenario
      in which vaccination costs less than 100,000 dollars per QALY gained is when 1)
      the unit cost of vaccination is less than 200 dollars, 2) the age at vaccination
      is less than 70 years, and 3) the duration of vaccine efficacy is more than 30
      years. RESULTS OF SENSITIVITY ANALYSIS: Vaccination would be more cost-effective
      in "younger" older adults (age 60 to 64 years) than in "older" older adults (age
      > or =80 years). Longer life expectancy and a higher level of vaccine efficacy
      offset a lower risk for herpes zoster in the younger group. Other factors
      influencing cost-effectiveness include quality-of-life adjustments for acute
      zoster, unit cost of the vaccine, risk for herpes zoster, and duration of vaccine
      efficacy. LIMITATIONS: The effectiveness of VZV vaccination remains uncertain
      beyond the median 3.1-year duration of follow-up in the Shingles Prevention
      Study. CONCLUSIONS: Varicella-zoster virus vaccination to prevent herpes zoster
      in older adults would increase QALYs compared with no vaccination. Resolution of
      uncertainties about the average quality-of-life effects of acute zoster and the
      duration of vaccine efficacy is needed to better determine the cost-effectiveness
      of zoster vaccination in older adults.

PMID- 16954358
TI  - Meal size, not body size, explains errors in estimating the calorie content of
      meals.
AB  - BACKGROUND: Although most people underestimate the calories they consume during a
      meal or during the day, calorie underestimation is especially extreme among
      overweight persons. The reason for this systematic bias is unknown. OBJECTIVE: To
      investigate whether the association between calorie underestimation and body mass
      reflects a tendency for all persons to underestimate calories as the size of a
      meal increases. DESIGN: Overweight and normal-weight adults estimated the number
      of calories of a fast-food meal they had ordered and eaten (study 1) or of 15
      fast-food meals that were chosen by the experimenter (study 2) in a randomized,
      controlled trial. Their estimations were compared with the actual number of
      calories of the meals. SETTING: Study 1 was a field study conducted in fast-food
      restaurants in 3 medium-sized midwestern U.S. cities. Study 2 was conducted in a
      laboratory at a major U.S. research university. PARTICIPANTS: Study 1 involved
      105 lunchtime diners (average body mass index [BMI], 24.2 kg/m2 [range, 17.2 to
      33.5 kg/m2]). Study 2 involved 40 undergraduate students (average BMI, 23.2 kg/m2
      [range, 16.1 to 32.3 kg/m2]). MEASUREMENTS: Participants were asked to estimate
      the number of calories in a fast-food meal they had ordered and eaten (study 1)
      or in 15 sizes of the same fast-food meal (study 2). The actual number of
      calories in the meals in the field study was obtained by unobtrusively recording
      the food that was ordered (identified from the wrappings and containers). Weight
      and height were self-reported. RESULTS: Although participants strongly
      underestimated the number of calories in larger meals (by -38.0% in study 1 and
      by -22.6% in study 2), they almost perfectly estimated the number of calories in
      smaller meals (by -2.9% in study 1 and by 3.0% in study 2). After the authors
      controlled for body weight-related differences in meal size, the calorie
      estimations of normal-weight and overweight participants were identical in both
      studies. LIMITATIONS: These studies examined fast-food meals. Weight and height
      were self-reported. There were too few observations to distinguish between obese
      (BMI > or =30 kg/m2) and overweight (BMI >25 kg/m2 but <30 kg/m2) participants.
      CONCLUSIONS: Greater underestimation of calories by overweight persons is a
      consequence of their tendency to consume larger meals. Calorie underestimation is
      related to meal size, not body size.

PMID- 16954360
TI  - Update in infectious diseases.

PMID- 16954359
TI  - The effect of polyphenols in olive oil on heart disease risk factors: a
      randomized trial.
AB  - BACKGROUND: Virgin olive oils are richer in phenolic content than refined olive
      oil. Small, randomized, crossover, controlled trials on the antioxidant effect of
      phenolic compounds from real-life daily doses of olive oil in humans have yielded
      conflicting results. Little information is available on the effect of the
      phenolic compounds of olive oil on plasma lipid levels. No international study
      with a large sample size has been done. OBJECTIVE: To evaluate whether the
      phenolic content of olive oil further benefits plasma lipid levels and lipid
      oxidative damage compared with monounsaturated acid content. DESIGN: Randomized,
      crossover, controlled trial. SETTING: 6 research centers from 5 European
      countries. PARTICIPANTS: 200 healthy male volunteers. MEASUREMENTS: Glucose
      levels, plasma lipid levels, oxidative damage to lipid levels, and endogenous and
      exogenous antioxidants at baseline and before and after each intervention.
      INTERVENTION: In a crossover study, participants were randomly assigned to 3
      sequences of daily administration of 25 mL of 3 olive oils. Olive oils had low
      (2.7 mg/kg of olive oil), medium (164 mg/kg), or high (366 mg/kg) phenolic
      content but were otherwise similar. Intervention periods were 3 weeks preceded by
      2-week washout periods. RESULTS: A linear increase in high-density lipoprotein
      (HDL) cholesterol levels was observed for low-, medium-, and high-polyphenol
      olive oil: mean change, 0.025 mmol/L (95% CI, 0.003 to 0.05 mmol/L), 0.032 mmol/L
      (CI, 0.005 to 0.05 mmol/L), and 0.045 mmol/L (CI, 0.02 to 0.06 mmol/L),
      respectively. Total cholesterol-HDL cholesterol ratio decreased linearly with the
      phenolic content of the olive oil. Triglyceride levels decreased by an average of
      0.05 mmol/L for all olive oils. Oxidative stress markers decreased linearly with
      increasing phenolic content. Mean changes for oxidized low-density lipoprotein
      levels were 1.21 U/L (CI, -0.8 to 3.6 U/L), -1.48 U/L (-3.6 to 0.6 U/L), and 
      3.21 U/L (-5.1 to -0.8 U/L) for the low-, medium-, and high-polyphenol olive oil,
      respectively. LIMITATIONS: The olive oil may have interacted with other dietary
      components, participants' dietary intake was self-reported, and the intervention
      periods were short. CONCLUSIONS: Olive oil is more than a monounsaturated fat.
      Its phenolic content can also provide benefits for plasma lipid levels and
      oxidative damage. International Standard Randomised Controlled Trial number:
      ISRCTN09220811.

PMID- 16954361
TI  - Do OSCAR winners live longer than less successful peers? A reanalysis of the
      evidence.
AB  - In an article published in Annals of Internal Medicine in 2001, Redelmeier and
      Singh reported that Academy Award-winning actors and actresses lived almost 4
      years longer than their less successful peers. However, the statistical method
      used to derive this statistically significant difference gave winners an unfair
      advantage because it credited an Oscar winner's years of life before winning
      toward survival subsequent to winning. When the authors of the current article
      reanalyzed the data using methods that avoided this "immortal time" bias, the
      survival advantage was closer to 1 year and was not statistically significant.
      The type of bias in Redelmeier and Singh's study is not limited to longevity
      comparisons of persons who reach different ranks within their profession; it can,
      and often does, occur in nonexperimental studies of life- or time-extending
      benefits of medical interventions. The current authors suggest ways in which
      researchers and readers may avoid and recognize this bias.

PMID- 16954362
TI  - Shingles vaccine: effective and costly or cost-effective?

PMID- 16954363
TI  - Free fall.

PMID- 16954364
TI  - Reanalysis of survival of OSCAR winners.

PMID- 16954366
TI  - Cryptogenic stroke and patent foramen ovale.

PMID- 16954367
TI  - Poorly controlled cardiovascular risk factors and ICD-9-CM codes.

PMID- 16954368
TI  - Corporate strategies for computerization.

PMID- 16954369
TI  - Differential impact of Ink4a and Arf on hematopoietic stem cells and their bone
      marrow microenvironment in Bmi1-deficient mice.
AB  - The polycomb group (PcG) protein Bmi1 plays an essential role in the self-renewal
      of hematopoietic and neural stem cells. Derepression of the Ink4a/Arf gene locus
      has been largely attributed to Bmi1-deficient phenotypes in the nervous system.
      However, its role in hematopoietic stem cell (HSC) self-renewal remained
      undetermined. In this study, we show that derepressed p16(Ink4a) and p19(Arf) in
      Bmi1-deficient mice were tightly associated with a loss of self-renewing HSCs.
      The deletion of both Ink4a and Arf genes substantially restored the self-renewal
      capacity of Bmi1(-/-) HSCs. Thus, Bmi1 regulates HSCs by acting as a critical
      failsafe against the p16(Ink4a)- and p19(Arf)-dependent premature loss of HSCs.
      We further identified a novel role for Bmi1 in the organization of a functional
      bone marrow (BM) microenvironment. The BM microenvironment in Bmi1(-/-) mice
      appeared severely defective in supporting hematopoiesis. The deletion of both
      Ink4a and Arf genes did not considerably restore the impaired BM
      microenvironment, leading to a sustained postnatal HSC depletion in Bmi1(-/
      )Ink4a-Arf(-/-) mice. Our findings unveil a differential role of derepressed
      Ink4a and Arf on HSCs and their BM microenvironment in Bmi1-deficient mice.
      Collectively, Bmi1 regulates self-renewing HSCs in both cell-autonomous and
      nonautonomous manners.

PMID- 16954370
TI  - B-1 B lymphocytes require Blimp-1 for immunoglobulin secretion.
AB  - B-1 B cells produce circulating natural antibodies that provide "innate-like"
      protection against bacterial and viral pathogens. They also provide adaptive
      responses to blood and air-borne pathogens. B lymphocyte-induced maturation
      protein 1 (Blimp-1) is a transcriptional repressor that is required for the
      formation of B-2-derived antibody-secreting plasma cells. In this study, we used
      mice lacking Blimp-1 in the B cell lineage to show that Blimp-1 is not necessary
      for the formation or self-renewal of B-1 B cells but that Blimp-1 is required for
      normal immunoglobulin (Ig) secretion by B-1 cells. B-1 cells lacking Blimp-1 do
      not repress Pax5 mRNA and do not induce X-box binding protein 1, and mu secreted
      mRNA normally, showing that B-1 and B-2 cells both use a common pathway for Ig
      secretion. Blimp-1-deficient B-1 B cells are also defective in providing early
      protection against influenza infection.

PMID- 16954371
TI  - Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells
      restores contractile function to the infarcted myocardium.
AB  - Cellular cardiomyoplasty is an attractive option for the treatment of severe
      heart failure. It is, however, still unclear and controversial which is the most
      promising cell source. Therefore, we investigated and examined the fate and
      functional impact of bone marrow (BM) cells and embryonic stem cell (ES cell)
      derived cardiomyocytes after transplantation into the infarcted mouse heart. This
      proved particularly challenging for the ES cells, as their enrichment into
      cardiomyocytes and their long-term engraftment and tumorigenicity are still
      poorly understood. We generated transgenic ES cells expressing puromycin
      resistance and enhanced green fluorescent protein cassettes under control of a
      cardiac-specific promoter. Puromycin selection resulted in a highly purified
      (>99%) cardiomyocyte population, and the yield of cardiomyocytes increased 6-10
      fold because of induction of proliferation on purification. Long-term engraftment
      (4-5 months) was observed when co-transplanting selected ES cell-derived
      cardiomyocytes and fibroblasts into the injured heart of syngeneic mice, and no
      teratoma formation was found (n = 60). Although transplantation of ES cell
      derived cardiomyocytes improved heart function, BM cells had no positive effects.
      Furthermore, no contribution of BM cells to cardiac, endothelial, or smooth
      muscle neogenesis was detected. Hence, our results demonstrate that ES-based cell
      therapy is a promising approach for the treatment of impaired myocardial function
      and provides better results than BM-derived cells.

PMID- 16954372
TI  - PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection.
AB  - Here, we report on the expression of programmed death (PD)-1 on human virus
      specific CD8(+) T cells and the effect of manipulating signaling through PD-1 on
      the survival, proliferation, and cytokine function of these cells. PD-1
      expression was found to be low on naive CD8(+) T cells and increased on memory
      CD8(+) T cells according to antigen specificity. Memory CD8(+) T cells specific
      for poorly controlled chronic persistent virus (HIV) more frequently expressed PD
      1 than memory CD8(+) T cells specific for well-controlled persistent virus
      (cytomegalovirus) or acute (vaccinia) viruses. PD-1 expression was independent of
      maturational markers on memory CD8(+) T cells and was not directly associated
      with an inability to produce cytokines. Importantly, the level of PD-1 surface
      expression was the primary determinant of apoptosis sensitivity of virus-specific
      CD8(+) T cells. Manipulation of PD-1 led to changes in the ability of the cells
      to survive and expand, which, over several days, affected the number of cells
      expressing cytokines. Therefore, PD-1 is a major regulator of apoptosis that can
      impact the frequency of antiviral T cells in chronic infections such as HIV, and
      could be manipulated to improve HIV-specific CD8(+) T cell numbers, but possibly
      not all functions in vivo.

PMID- 16954373
TI  - Aberrant promoter methylation of the ABCG2 gene in renal carcinoma.
AB  - ABCG2 is a ubiquitous ATP-binding cassette transmembrane protein that is
      important in clinical drug resistance. Little is known about the mechanism(s)
      regulating the expression of ABCG2. We hypothesized that DNA methylation could
      play a role in the epigenetic regulation of ABCG2 gene expression. The promoter
      methylation status of three renal carcinoma cell lines was assessed with
      restriction enzyme digestion-coupled PCR and bisulfite genomic sequencing. Both
      UOK121 and UOK143, with known methylation of the VHL promoter, showed induction
      of ABCG2 expression after 5-aza-2'-deoxycytidine (5-aza-dC) treatment, suggesting
      that aberrant methylation of the ABCG2 gene was associated with gene silencing.
      In vitro methylation of the ABCG2 promoter-driven luciferase reporter vector
      resulted in a significant inhibition of transcription. Our data suggested that
      the ABCG2 gene is regulated coordinately at both histone and DNA levels. A
      chromatin immunoprecipitation assay demonstrated that the methylated promoter in
      UOK121 and UOK143, but not the unmethylated one in UOK181, is associated with the
      methyl CpG binding domain proteins (MBDs), MBD2 and MeCP2. Histone deacetylase 1
      and a corepressor, mSin3A, were identified binding to the promoter region
      containing the CpG island, thereby suppressing ABCG2 transcription. Reactivation
      of ABCG2 was achieved by treatment with 5-aza-dC, a demethylating agent,
      concomitant with the release of MBDs from the promoter. Furthermore, the
      association of methylated lysine 9 on histone H3, a hallmark of promoter
      methylation, with the promoter was reduced following 5-aza-dC treatment. These
      data suggest that DNA methylation-dependent formation of a repressor complex in
      the CpG island contributes to inactivation of ABCG2.

PMID- 16954374
TI  - Mutant myocilin nonsecretion in vivo is not sufficient to cause glaucoma.
AB  - Glaucoma is a leading cause of blindness, affecting over 70 million people
      worldwide. Vision loss is the result of death of the retinal ganglion cells. The
      best-known risk factor for glaucoma is an elevated intraocular pressure (IOP);
      however, factors leading to IOP elevation are poorly understood. Mutations in the
      MYOC gene are an important cause of open-angle glaucoma. Over 70 MYOC mutations
      have been identified, and they lead to approximately 5% of all primary open-angle
      glaucoma cases. Nevertheless, the pathogenic mechanisms by which these mutations
      elevate IOP are presently unclear. Data suggest that a dominant interfering
      effect of misfolded mutant MYOC molecules may be pathogenic. To test this
      hypothesis, we have generated mice carrying a mutant allele of Myoc that is
      analogous to a human mutation that leads to aggressive glaucoma in patients. We
      show that mutant MYOC is not secreted into the aqueous humor. Instead of being
      secreted, mutant MYOC accumulates within the iridocorneal angle of the eye,
      consistent with the behavior of abnormally folded protein. Surprisingly, the
      accumulated mutant protein does not activate the unfolded protein response and
      lead to elevated intraocular pressure or glaucoma in aged mice of different
      strains. These data suggest that production, apparent misfolding, and
      nonsecretion of mutant MYOC are not, by themselves, sufficient to cause glaucoma
      in vivo.

PMID- 16954375
TI  - Destabilization of interleukin-6 mRNA requires a putative RNA stem-loop
      structure, an AU-rich element, and the RNA-binding protein AUF1.
AB  - Interleukin-6 mRNA is unstable and degraded with a half-life of 30 min.
      Instability determinants can entirely be attributed to the 3' untranslated
      region. By grafting segments of this region to stable green fluorescent protein
      mRNA and subsequent scanning mutagenesis, we have identified two conserved
      elements, which together account for most of the instability. The first
      corresponds to a short noncanonical AU-rich element. The other, 80 nucleotides
      further 5', comprises a sequence predicted to form a stem-loop structure. Neither
      element alone was sufficient to confer full instability, suggesting that they
      might cooperate. Overexpression of myc-tagged AUF1 p37 and p42 isoforms as well
      as suppression of endogenous AUF1 by RNA interference stabilized interleukin-6
      mRNA. Both effects required the AU-rich instability element. Similarly, the
      proteasome inhibitor MG132 stabilized interleukin-6 mRNA probably through an
      increase of AUF1 levels. The mRNA coimmunoprecipitated specifically with myc
      tagged AUF1 p37 and p42 in cell extracts but only when the AU-rich instability
      element was present. These results indicate that AUF1 binds to the AU-rich
      element in vivo and promotes IL-6 mRNA degradation.

PMID- 16954376
TI  - Binding of YY1 to the proximal region of the murine beta interferon promoter is
      essential to allow CBP recruitment and K8H4/K14H3 acetylation on the promoter
      region after virus infection.
AB  - Virus-induced activation of the beta interferon (IFN-beta) gene requires orderly
      recruitment of chromatin-remodeling complexes and time-regulated acetylation of
      histone residues K8H4 and K14H3 on the promoter region. We have previously shown
      that transcription factor Yin Yang 1 (YY1) binds the murine IFN-beta promoter at
      two sites (-122 and -90) regulating promoter transcriptional capacity with a dual
      activator/repressor role. In this work we demonstrate that both YY1 -122 and -90
      sites are required for CBP recruitment and K8H4/K14H3 acetylation to take place
      on the IFN-beta promoter region after virus infection. A single point mutation
      introduced at either one of these two sites inhibiting YY1 binding completely
      disrupted CBP recruitment and K8H4/K14H3 acetylation independently of HMGI or
      IRF3 binding to the promoter. We have previously demonstrated that YY1 represses
      the transcriptional capacity of the IFN-beta promoter through its -90 site via
      histone deacetylation. Here we demonstrate that, in vivo, the binding of YY1 to
      the -90 site is constant all through virus infection whereas the binding of YY1
      to the -122 site is activated after infection. We discuss here the capacity of
      YY1 to either repress (through histone deacetylase recruitment) or activate
      (through CBP recruitment) IFN-beta gene expression according to the occupancy of
      either only its -90 site or both its -122 and -90 sites.

PMID- 16954378
TI  - Cold shock domain family members YB-1 and MSY4 share essential functions during
      murine embryogenesis.
AB  - Three cold shock domain (CSD) family members (YB-1, MSY2, and MSY4) exist in
      vertebrate species ranging from frogs to humans. YB-1 is expressed throughout
      embryogenesis and is ubiquitously expressed in adult animals; it protects cells
      from senescence during periods of proliferative stress. YB-1-deficient embryos
      die unexpectedly late in embryogenesis (embryonic day 18.5 [E18.5] to postnatal
      day 1) with a runting phenotype. We have now determined that MSY4, but not MSY2,
      is also expressed during embryogenesis; its abundance declines substantially from
      E9.5 to E17.5 and is undetectable on postnatal day 1(adult mice express MSY4 in
      testes only). Whole-mount analysis revealed similar patterns of YB-1 and MSY4 RNA
      expression in E11.5 embryos. To determine whether MSY4 delays the death of YB-1
      deficient embryos, we created and analyzed MSY4-deficient mice and then generated
      YB-1 and MSY4 double-knockout embryos. MSY4 is dispensable for normal development
      and survival, but the testes of adult mice have excessive spermatocyte apoptosis
      and seminiferous tubule degeneration. Embryos doubly deficient for YB-1 and MSY4
      are severely runted and die much earlier (E8.5 to E11.5) than YB-1-deficient
      embryos, suggesting that MSY4 indeed shares critical cellular functions with YB-1
      in the embryonic tissues where they are coexpressed.

PMID- 16954377
TI  - Identification of yin-yang regulators and a phosphorylation consensus for male
      germ cell-associated kinase (MAK)-related kinase.
AB  - MAK (male germ cell-associated protein kinase) and MRK/ICK (MAK-related
      kinase/intestinal cell kinase) are human homologs of Ime2p in Saccharomyces
      cerevisiae and of Mde3 and Pit1 in Schizosaccharomyces pombe and are similar to
      human cyclin-dependent kinase 2 (CDK2) and extracellular signal-regulated kinase
      2 (ERK2). MAK and MRK require dual phosphorylation in a TDY motif catalyzed by an
      unidentified human threonine kinase and tyrosine autophosphorylation. Herein, we
      establish that human CDK-related kinase CCRK (cell cycle-related kinase) is an
      activating T157 kinase for MRK, whereas active CDK7/cyclin H/MAT1 complexes
      phosphorylate CDK2 but not MRK. Protein phosphatase 5 (PP5) interacts with MRK in
      a complex and dephosphorylates MRK at T157 in vitro and in situ. Thus, CCRK and
      PP5 are yin-yang regulators of T157 phosphorylation. To determine a substrate
      consensus, we screened a combinatorial peptide library with active MRK. MRK
      preferentially phosphorylates R-P-X-S/T-P sites, with the preference for arginine
      at position -3 (P-3) being more stringent than for prolines at P-2 and P+1. Using
      the consensus, we identified a putative phosphorylation site (RPLT(1080)S) for
      MRK in human Scythe, an antiapoptotic protein that interacts with MRK. MRK
      phosphorylates Scythe at T1080 in vitro as determined by site-directed
      mutagenesis and mass spectrometry, supporting the consensus and suggesting Scythe
      as a physiological substrate for MRK.

PMID- 16954379
TI  - Specific differentially methylated domain sequences direct the maintenance of
      methylation at imprinted genes.
AB  - Landmark features of imprinted genes are differentially methylated domains
      (DMDs), in which one parental allele is methylated on CpG dinucleotides and the
      opposite allele is unmethylated. Genetic experiments in the mouse have shown that
      DMDs are required for the parent-specific expression of linked clusters of
      imprinted genes. To understand the mechanism whereby the differential methylation
      is established and maintained, we analyzed a series of transgenes containing DMD
      sequences and showed that imperfect tandem repeats from DMDs associated with the
      Snurf/Snrpn, Kcnq1, and Igf2r gene clusters govern transgene imprinting. For the
      Igf2r DMD the minimal imprinting signal is two unit copies of the tandem repeat.
      This imprinted transgene behaves identically to endogenous imprinted genes in
      Dnmt1o and Dnmt3L mutant mouse backgrounds. The primary function of the
      imprinting signal within the transgene DMD is to maintain, during embryogenesis
      and a critical period of genomic reprogramming, parent-specific DNA methylation
      states established in the germ line. This work advances our understanding of the
      imprinting mechanism by defining a genomic signal that dependably perpetuates an
      epigenetic state during postzygotic development.

PMID- 16954380
TI  - Rapid loss of intestinal crypts upon conditional deletion of the Wnt/Tcf-4 target
      gene c-Myc.
AB  - Inhibition of the mutationally activated Wnt cascade in colorectal cancer cell
      lines induces a rapid G1 arrest and subsequent differentiation. This arrest can
      be overcome by maintaining expression of a single Tcf4 target gene, the proto
      oncogene c-Myc. Since colorectal cancer cells share many molecular
      characteristics with proliferative crypt progenitors, we have assessed the
      physiological role of c-Myc in adult crypts by conditional gene deletion. c-Myc
      deficient crypts are lost within weeks and replaced by c-Myc-proficient crypts
      through a fission process of crypts that have escaped gene deletion. Although c
      Myc(-/-) crypt cells remain in the cell cycle, they are on average much smaller
      than wild-type cells, cycle slower, and divide at a smaller cell size. c-Myc
      appears essential for crypt progenitor cells to provide the necessary
      biosynthetic capacity to successfully progress through the cell cycle.

PMID- 16954381
TI  - The KAP1 corepressor functions to coordinate the assembly of de novo HP1
      demarcated microenvironments of heterochromatin required for KRAB zinc finger
      protein-mediated transcriptional repression.
AB  - KAP1/TIF1beta is proposed to be a universal corepressor protein for the KRAB zinc
      finger protein (KRAB-zfp) superfamily of transcriptional repressors. To
      characterize the role of KAP1 and KAP1-interacting proteins in transcriptional
      repression, we investigated the regulation of stably integrated reporter
      transgenes by hormone-responsive KRAB and KAP1 repressor proteins. Here, we
      demonstrate that depletion of endogenous KAP1 levels by small interfering RNA
      (siRNA) significantly inhibited KRAB-mediated transcriptional repression of a
      chromatin template. Similarly, reduction in cellular levels of
      HP1alpha/beta/gamma and SETDB1 by siRNA attenuated KRAB-KAP1 repression. We also
      found that direct tethering of KAP1 to DNA was sufficient to repress
      transcription of an integrated transgene. This activity is absolutely dependent
      upon the interaction of KAP1 with HP1 and on an intact PHD finger and bromodomain
      of KAP1, suggesting that these domains function cooperatively in transcriptional
      corepression. The achievement of the repressed state by wild-type KAP1 involves
      decreased recruitment of RNA polymerase II, reduced levels of histone H3 K9
      acetylation and H3K4 methylation, an increase in histone occupancy, enrichment of
      trimethyl histone H3K9, H3K36, and histone H4K20, and HP1 deposition at proximal
      regulatory sequences of the transgene. A KAP1 protein containing a mutation of
      the HP1 binding domain failed to induce any change in the histone modifications
      associated with DNA sequences of the transgene, implying that HP1-directed
      nuclear compartmentalization is required for transcriptional repression by the
      KRAB/KAP1 repression complex. The combination of these data suggests that KAP1
      functions to coordinate activities that dynamically regulate changes in histone
      modifications and deposition of HP1 to establish a de novo microenvironment of
      heterochromatin, which is required for repression of gene transcription by KRAB
      zfps.

PMID- 16954382
TI  - Cotranscriptional recruitment to the mRNA export receptor Mex67p contributes to
      nuclear pore anchoring of activated genes.
AB  - Transcription activation of some Saccharomyces cerevisiae genes is paralleled by
      their repositioning to the nuclear periphery, but the mechanism underlying gene
      anchoring is poorly defined. We show that the nuclear pore complex-associated
      Mlp1p and the shuttling mRNA export receptor Mex67p contribute to the stable
      association of the activated GAL10 and HSP104 genes with the nuclear periphery.
      However, we find no obligatory link between gene positioning and gene expression.
      Furthermore, gene anchoring correlates with the cotranscriptional recruitment of
      Mex67p to transcribing genes. Notably, the association of Mex67p with chromatin
      is not mediated by RNA. Interestingly, a mutant GAL2 gene lacking the coding
      region is still able to recruit Mex67p upon transcriptional activation and to
      relocate to the nuclear periphery. Together these data suggest that, at least for
      GAL2, nascent messenger ribonucleoprotein does not play a major role in gene
      anchoring and that the early recruitment of Mex67p contributes to gene
      repositioning by virtue of an RNA-independent process.

PMID- 16954383
TI  - Essential role for cyclin D3 in granulocyte colony-stimulating factor-driven
      expansion of neutrophil granulocytes.
AB  - The proliferation of neutrophil granulocyte lineage is driven largely by
      granulocyte colony-stimulating factor (G-CSF) acting via the G-CSF receptors. In
      this study, we show that mice lacking cyclin D3, a component of the core cell
      cycle machinery, are refractory to stimulation by the G-CSF. Consequently, cyclin
      D3-null mice display deficient maturation of granulocytes in the bone marrow and
      have reduced levels of neutrophil granulocytes in their peripheral blood. The
      mutant mice are unable to mount a normal response to bacterial challenge and
      succumb to microbial infections. In contrast, the expansion of hematopoietic stem
      cells and lineage-committed myeloid progenitors proceeds relatively normally in
      mice lacking cyclin D3, revealing that the requirement for cyclin D3 function
      operates at later stages of neutrophil development. Importantly, we verified that
      this requirement is specific to cyclin D3, as mice lacking other G(1) cyclins
      (D1, D2, E1, or E2) display normal granulocyte counts. Our analyses revealed that
      in the bone marrow cells of wild-type mice, activation of the G-CSF receptor
      leads to upregulation of cyclin D3. Collectively, these results demonstrate that
      cyclin D3 is an essential cell cycle recipient of G-CSF signaling, and they
      provide a molecular link of how G-CSF-dependent signaling triggers cell
      proliferation.

PMID- 16954384
TI  - Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in
      embryonic stem cells.
AB  - Although the POU transcription factor Oct3/4 is pivotal in maintaining self
      renewal of embryonic stem (ES) cells, little is known of its molecular
      mechanisms. We previously reported that the N-terminal transactivation domain of
      Oct3/4 is required for activation of Lefty1 expression (H. Niwa, S. Masui, I.
      Chambers, A. G. Smith, and J. Miyazaki, Mol. Cell. Biol. 22:1526-1536, 2002).
      Here we test whether Lefty1 is a direct target of Oct3/4. We identified an ES
      cell-specific enhancer upstream of the Lefty1 promoter that contains binding
      sites for Oct3/4 and Sox2. Unlike other known Oct3/4-Sox2-dependent enhancers,
      however, this enhancer element could not be activated by Oct3/4 and Sox2 in
      differentiated cells. By functional screening of ES-specific transcription
      factors, we found that Kruppel-like factor 4 (Klf4) cooperates with Oct3/4 and
      Sox2 to activate Lefty1 expression, and that Klf4 acts as a mediating factor that
      specifically binds to the proximal element of the Lefty1 promoter. DNA microarray
      analysis revealed that a subset of putative Oct3/4 target genes may be regulated
      in the same manner. Our findings shed light on a novel function of Oct3/4 in ES
      cells.

PMID- 16954385
TI  - Differential regulation of short- and long-tract gene conversion between sister
      chromatids by Rad51C.
AB  - The Rad51 paralog Rad51C has been implicated in the control of homologous
      recombination. To study the role of Rad51C in vivo in mammalian cells, we
      analyzed short-tract and long-tract gene conversion between sister chromatids in
      hamster Rad51C(-/-) CL-V4B cells in response to a site-specific chromosomal
      double-strand break. Gene conversion was inefficient in these cells and was
      specifically restored by expression of wild-type Rad51C. Surprisingly, gene
      conversions in CL-V4B cells were biased in favor of long-tract gene conversion,
      in comparison to controls expressing wild-type Rad51C. These long-tract events
      were not associated with crossing over between sister chromatids. Analysis of
      gene conversion tract lengths in CL-V4B cells lacking Rad51C revealed a bimodal
      frequency distribution, with almost all gene conversions being either less than 1
      kb or greater than 3.2 kb in length. These results indicate that Rad51C plays a
      pivotal role in determining the "choice" between short- and long-tract gene
      conversion and in suppressing gene amplifications associated with sister
      chromatid recombination.

PMID- 16954386
TI  - Point mutations in two EVI1 Zn fingers abolish EVI1-GATA1 interaction and allow
      erythroid differentiation of murine bone marrow cells.
AB  - EVI1 is an aggressive nuclear oncoprotein deregulated by recurring chromosomal
      abnormalities in myelodysplastic syndrome (MDS). The expression of the
      corresponding gene is a very poor prognostic marker for MDS patients and is
      associated with severe defects of the erythroid lineage. We have recently shown
      that the constitutive expression of EVI1 in murine bone marrow results in a fatal
      disease with features characteristic of MDS, including anemia, dyserythropoiesis,
      and dysmegakaryopoiesis. These lineages are regulated by the DNA-binding
      transcription factor GATA1. EVI1 has two zinc finger domains containing seven
      motifs at the N terminus and three motifs at the C terminus. Supported by results
      of assays utilizing synthetic DNA promoters, it was earlier proposed that
      erythroid-lineage repression by EVI1 is based on the ability of this protein to
      compete with GATA1 for DNA-binding sites, resulting in repression of gene
      activation by GATA1. Here, however, we show that EVI1 is unable to bind to
      classic GATA1 sites. To understand the mechanism utilized by EVI1 to repress
      erythropoiesis, we used a combination of biochemical assays, mutation analyses,
      and in vitro bone marrow differentiation. The results indicate that EVI1
      interacts directly with the GATA1 protein rather than the DNA sequence. We
      further show that this protein-protein interaction blocks efficient recognition
      or binding to DNA by GATA1. Point mutations that disrupt the geometry of two zinc
      fingers of EVI1 abolish the protein-protein interaction, leading to normal
      erythroid differentiation of normal murine bone marrow in vitro.

PMID- 16954387
TI  - Notch1 contributes to mouse T-cell leukemia by directly inducing the expression
      of c-myc.
AB  - Recent work with mouse models and human leukemic samples has shown that gain-of
      function mutation(s) in Notch1 is a common genetic event in T-cell acute
      lymphoblastic leukemia (T-ALL). The Notch1 receptor signals through a gamma
      secretase-dependent process that releases intracellular Notch1 from the membrane
      to the nucleus, where it forms part of a transcriptional activator complex. To
      identify Notch1 target genes in leukemia, we developed mouse T-cell leukemic
      lines that express intracellular Notch1 in a doxycycline-dependent manner. Using
      gene expression profiling and chromatin immunoprecipitation, we identified c-myc
      as a novel, direct, and critical Notch1 target gene in T-cell leukemia. c-myc
      mRNA levels are increased in primary mouse T-cell tumors that harbor Notch1
      mutations, and Notch1 inhibition decreases c-myc mRNA levels and inhibits
      leukemic cell growth. Retroviral expression of c-myc, like intracellular Notch1,
      rescues the growth arrest and apoptosis associated with gamma-secretase inhibitor
      treatment or Notch1 inhibition. Consistent with these findings, retroviral
      insertional mutagenesis screening of our T-cell leukemia mouse model revealed
      common insertions in either notch1 or c-myc genes. These studies define the
      Notch1 molecular signature in mouse T-ALL and importantly provide mechanistic
      insight as to how Notch1 contributes to human T-ALL.

PMID- 16954388
TI  - A gradient of epidermal growth factor receptor signaling determines the
      sensitivity of rbf1 mutant cells to E2F-dependent apoptosis.
AB  - The inactivation of retinoblastoma (Rb) family members sensitizes cells to
      apoptosis. This cell death affects the development of mutant animals and also
      provides a critical constraint to the malignant potential of Rb mutant tumor
      cells. The extent of apoptosis caused by the inactivation of Rb is highly cell
      type and tissue specific, but the underlying reasons for this variation are
      poorly understood. Here, we characterize a specific time and place during
      Drosophila melanogaster development where rbf1 mutant cells are exquisitely
      sensitive to apoptosis. During the third larval instar, many rbf1 mutant cells
      undergo E2F-dependent cell death in the morphogenetic furrow. Surprisingly, this
      pattern of apoptosis is not caused by inappropriate cell cycle progression but
      instead involves the action of Argos, a secreted protein that negatively
      regulates Drosophila epidermal growth factor receptor (EGFR [DER]) activity.
      Apoptosis of rbf1 mutant cells is suppressed by the activation of DER, ras, or
      raf or by the inactivation of argos, sprouty, or gap1, and inhibition of DER
      strongly enhances apoptosis in rbf1 mutant discs. We show that RBF1 and a
      DER/ras/raf signaling pathway cooperate in vivo to suppress E2F-dependent
      apoptosis and that the loss of RBF1 alters a normal program of cell death that is
      controlled by Argos and DER. These results demonstrate that a gradient of
      DER/ras/raf signaling that occurs naturally during development provides the
      contextual signals that determine when and where the inactivation of rbf1 results
      in dE2F1-dependent apoptosis.

PMID- 16954389
TI  - Identification of new human origins of DNA replication by an origin-trapping
      assay.
AB  - Metazoan genomes contain thousands of replication origins, but only a limited
      number have been characterized so far. We developed a two-step origin-trapping
      assay in which human chromatin fragments associated with origin recognition
      complex (ORC) in vivo were first enriched by chromatin immunoprecipitation. In a
      second step, these fragments were screened for transient replication competence
      in a plasmid-based assay utilizing the Epstein-Barr virus latent origin oriP.
      oriP contains two elements, an origin (dyad symmetry element [DS]) and the family
      of repeats, that when associated with the viral protein EBNA1 facilitate
      extrachromosomal stability. Insertion of the ORC-binding human DNA fragments in
      oriP plasmids in place of DS enabled us to screen functionally for their
      abilities to restore replication. Using the origin-trapping assay, we isolated
      and characterized five previously unknown human origins. The assay was validated
      with nascent strand abundance assays that confirm these origins as active
      initiation sites in their native chromosomal contexts. Furthermore, ORC and MCM2
      7 components localized at these origins during G(1) phase of the cell cycle but
      were not detected during mitosis. This finding extends the current understanding
      of origin-ORC dynamics by suggesting that replication origins must be
      reestablished during the early stages of each cell division cycle and that ORC
      itself participates in this process.

PMID- 16954390
TI  - Comparison of the inflammatory responses of human meningeal cells following
      challenge with Neisseria lactamica and with Neisseria meningitidis.
AB  - The rationale for the present study was to determine how different species of
      bacteria interact with cells of the human meninges in order to gain information
      that would have broad relevance to understanding aspects of the innate immune
      response in the brain. Neisseria lactamica is an occasional cause of meningitis
      in humans, and in this study we investigated the in vitro interactions between N.
      lactamica and cells derived from the leptomeninges in comparison with the closely
      related organism Neisseria meningitidis, a major cause of meningitis worldwide.
      N. lactamica adhered specifically to meningioma cells, but the levels of
      adherence were generally lower than those with N. meningitidis. Meningioma cells
      challenged with N. lactamica and N. meningitidis secreted significant amounts of
      the proinflammatory cytokine interleukin-6 (IL-6), the C-X-C chemokine IL-8, and
      the C-C chemokines monocyte chemoattractant protein 1 (MCP-1) and RANTES, but it
      secreted very low levels of the cytokine growth factor granulocyte-macrophage
      colony-stimulating factor (GM-CSF). Thus, meningeal cells are involved in the
      innate host response to Neisseria species that are capable of entering the
      cerebrospinal fluid. The levels of IL-8 and MCP-1 secretion induced by both
      bacteria were essentially similar. By contrast, N. lactamica induced
      significantly lower levels of IL-6 than N. meningitidis. Challenge with the
      highest concentration of N. lactamica (10(8) CFU) induced a small but significant
      down-regulation of RANTES secretion, which was not observed with lower
      concentrations of bacteria. N. meningitidis (10(6) to 10(8) CFU) also down
      regulated RANTES secretion, but this effect was significantly greater than that
      observed with N. lactamica. Although both bacteria were unable to invade
      meningeal cells directly, host cells remained viable on prolonged challenge with
      N. lactamica, whereas N. meningitidis induced death; the mechanism was
      overwhelming necrosis with no significant apoptosis. It is likely that
      differential expression of modulins between N. lactamica and N. meningitidis
      contributes to these observed differences in pathogenic potential.

PMID- 16954391
TI  - Cytosolic entry controls CD8+-T-cell potency during bacterial infection.
AB  - Interaction with host immunoreceptors during microbial infection directly impacts
      the magnitude of the ensuing innate immune response. How these signals affect the
      quality of the adaptive T-cell response remains poorly understood. Utilizing an
      engineered strain of the intracellular pathogen Listeria monocytogenes that
      infects cells but fails to escape from the phagosome, we demonstrate the
      induction of long-lived memory T cells that are capable of secondary expansion
      and effector function but are incapable of providing protective immunity. We
      demonstrate that microbial invasion of the cytosol is required for dendritic cell
      activation and integration of CD40 signaling, ultimately determining the ability
      of the elicited CD8+-T-cell pool to protect against lethal wild-type L.
      monocytogenes challenge. These results reveal a crucial role for phagosomal
      escape, not for delivery of antigen to the class I major histocompatibility
      complex pathway but for establishing the appropriate cellular context during CD8+
      T-cell priming.

PMID- 16954392
TI  - Susceptibility of prostate epithelial cells to Chlamydia muridarum infection and
      their role in innate immunity by recruitment of intracellular Toll-like receptors
      4 and 2 and MyD88 to the inclusion.
AB  - Although Chlamydia infections are widespread throughout the world, data about
      immunopathogenesis of genitourinary tract infections in males are very limited.
      In the present work we present an in vitro model of male genital tract-derived
      epithelial cells, more precisely prostate epithelial cells (PEC), to analyze if
      they are susceptible and able to respond to Chlamydia muridarum infection. Our
      results demonstrate that rat PEC are susceptible to C. muridarum infection and
      respond to this pathogen by up-regulating different proinflammatory cytokine and
      chemokine genes that could participate in the recruitment and local activation of
      immune cells, therefore influencing innate and adaptive immune responses during
      Chlamydia infection. Moreover, we analyzed the expression of Toll-like receptor 4
      (TLR4), TLR2, and related molecules on PEC and the effect of C. muridarum
      infection on their expression. Our results demonstrate that PEC express
      significant levels of TLR4, CD14, TLR2, and the adaptor molecule MyD88 and up
      regulate these proteins in response to C. muridarum infection. Indeed, TLR4,
      CD14, TLR2, and the adaptor MyD88 are specifically recruited to the vicinity of
      the bacterial inclusion, suggesting that these TLRs are actively engaged in
      signaling from this intracellular location in these cells. This is, to our
      knowledge, the first time that an in vitro model of infection with Chlamydia of
      male tract-derived epithelial cells has been achieved, and it provides the
      opportunity to determine how these cells respond and participate in modulating
      innate and adaptive immune response during Chlamydia infections.

PMID- 16954393
TI  - Tsetse fly saliva accelerates the onset of Trypanosoma brucei infection in a
      mouse model associated with a reduced host inflammatory response.
AB  - Tsetse flies (Glossina sp.) are the vectors that transmit African trypanosomes,
      protozoan parasites that cause human sleeping sickness and veterinary infections
      in the African continent. These blood-feeding dipteran insects deposit saliva at
      the feeding site that enables the blood-feeding process. Here we demonstrate that
      tsetse fly saliva also accelerates the onset of a Trypanosoma brucei infection.
      This effect was associated with a reduced inflammatory reaction at the site of
      infection initiation (reflected by a decrease of interleukin-6 [IL-6] and IL-12
      mRNA) as well as lower serum concentrations of the trypanocidal cytokine tumor
      necrosis factor. Variant-specific surface glycoprotein-specific antibody isotypes
      immunoglobulin M (IgM) and IgG2a, implicated in trypanosome clearance, were not
      suppressed. We propose that tsetse fly saliva accelerates the onset of
      trypanosome infection by inhibiting local and systemic inflammatory responses
      involved in parasite control.

PMID- 16954394
TI  - Protease activity, secretion, cell entry, cytotoxicity, and cellular targets of
      secreted autotransporter toxin of uropathogenic Escherichia coli.
AB  - The secreted autotransporter toxin (Sat), found predominantly in uropathogenic
      Escherichia coli, is a member of the SPATE (serine protease autotransporters of
      Enterobacteriaceae) family and, as such, has serine protease activity and causes
      cytopathic effects on various cell types. To assess the contribution of the
      serine protease active site to the mechanism of action of Sat, mutations were
      made in the first (S256I), in the second (S258A), or in both (S256I/S258A) serine
      residues within the active site motif. Mutations in the first or both serines
      reduced protease activity to background levels (P<0.001); a single mutation in
      the second serine reduced activity by 60% compared to wild type (P<0.001). After
      reversion of the S256I mutation to wild type (I256S), we confirmed S256 as the
      catalytically active serine. None of these mutations affected secretion of the
      mature passenger domain or release into the supernatant. The S256I mutation,
      however, abrogated the cytotoxicity of Sat on human bladder (UM-UC-3) and kidney
      (HEK 293) epithelial cells, characterized by rounding and elongation,
      respectively, and a high level of cell detachment. Moreover, S256 is essential
      for Sat to mediate cytoskeletal contraction and actin loss in host cells as well
      as to degrade specific membrane/cytoskeletal (fodrin and leukocyte function
      associated molecule 1) and nuclear [microtubule-associated proteins, LIM domain
      only protein 7, Rap GTPase-activating protein, poly(ADP-ribose) polymerase]
      proteins in vitro. Lastly, Sat was internalized by host cells and localized to
      the cytoskeletal fraction where membrane/cytoskeletal target proteins reside.

PMID- 16954395
TI  - Porphyromonas gingivalis galE is involved in lipopolysaccharide O-antigen
      synthesis and biofilm formation.
AB  - Porphyromonas gingivalis is a crucial component of complex plaque biofilms that
      form in the oral cavity, resulting in the progression of periodontal disease. To
      elucidate the mechanism of periodontal biofilm formation, we analyzed the
      involvement of several genes related to the synthesis of polysaccharides in P.
      gingivalis. Gene knockout P. gingivalis mutants were constructed by insertion of
      an ermF-ermAM cassette; among these mutants, the galE mutant showed some
      characteristic phenotypes involved in the loss of GalE activity. As expected, the
      galE mutant accumulated intracellular carbohydrates in the presence of 0.1%
      galactose and did not grow in the presence of galactose at a concentration
      greater than 1%, in contrast to the parental strain. Lipopolysaccharide (LPS)
      analysis indicated that the length of the O-antigen chain of the galE mutant was
      shorter than that of the wild type. It was also demonstrated that biofilms
      generated by the galE mutant had an intensity 4.5-fold greater than those of the
      wild type. Further, the galE mutant was found to be significantly susceptible to
      some antibiotics in comparison with the wild type. In addition, complementation
      of the galE mutation led to a partial recovery of the parental phenotypes. We
      concluded that the galE gene plays a pivotal role in the modification of LPS O
      antigen and biofilm formation in P. gingivalis and considered that our findings
      of a relationship between the function of the P. gingivalis galE gene and
      virulence phenotypes such as biofilm formation may provide clues for
      understanding the mechanism of pathogenicity in periodontal disease.

PMID- 16954396
TI  - Transgenic cows that produce recombinant human lactoferrin in milk are not
      protected from experimental Escherichia coli intramammary infection.
AB  - This is the first study describing an experimental mastitis model using
      transgenic cows expressing recombinant human lactoferrin (rhLf) in their milk.
      The aim of the study was to investigate the concentrations in milk and protective
      effects of bovine and recombinant human lactoferrin in experimental Escherichia
      coli mastitis. Experimental intramammary infection was induced in one udder
      quarter of seven first-lactating rhLf-transgenic cows and six normal cows, using
      an E. coli strain isolated from cows with clinical mastitis and known to be
      susceptible to Lf in vitro. Clinical signs were recorded during the experimental
      period, concentrations of human and bovine Lf and indicators of inflammation and
      bacterial counts were determined for milk, and concentrations of acute-phase
      proteins and tumor necrosis factor alpha were determined for sera and milk. Serum
      cortisol and blood hematological and biochemical parameters were also determined.
      Expression levels of rhLf in the milk of transgenic cows remained constant
      throughout the experiment (mean, 2.9 mg/ml). The high Lf concentrations in the
      milk of transgenic cows did not protect them from intramammary infection. All
      cows became infected and developed clinical mastitis. The rhLf-transgenic cows
      showed milder systemic signs and lower serum cortisol and haptoglobin
      concentrations than did controls. This may be explained by lipopolysaccharide
      neutralizing and immunomodulatory effects of the high Lf concentrations in their
      milk. However, Lf does not seem to be a very efficient protein for genetic
      engineering to enhance the mastitis resistance of dairy cows.

PMID- 16954397
TI  - Signal transduction and nuclear responses in Staphylococcus aureus-induced
      expression of human beta-defensin 3 in skin keratinocytes.
AB  - The human beta-defensin 3 (hBD-3) is an inducible epithelial peptide antibiotic
      that has potent antistaphylococcal activity. Infection of skin epithelial cells
      with viable Staphylococcus aureus, a common skin pathogen, induces increased gene
      expression of hBD-3 and other antimicrobial peptides. The aim of this study was
      to identify signaling pathways and nuclear responses that contribute to the gene
      expression of hBD-3 in primary human keratinocytes upon contact with S. aureus.
      Increased hBD-3 peptide was observed by immunofluorescence microscopy in
      keratinocytes exposed to S. aureus and to lipoteichoic acid (LTA). Both are
      ligands for the cell surface Toll-like receptor 2 (TLR2), and thus the
      contribution of TLR2 signaling in hBD-3 expression was examined. Functional
      inhibition of TLR2 prior to S. aureus stimulation significantly decreased hBD-3
      mRNA levels by 37%, attesting to the involvement of this surface receptor in the
      initial recognition and downstream signaling for hBD-3 expression. Treatment of
      keratinocytes with a p38 mitogen-activated protein kinase (MAPK) inhibitor prior
      to either S. aureus or LTA stimulation was associated with reduced hBD-3 mRNA
      transcripts and peptide. We also propose a role for the MAPK-regulated
      transcriptional activating protein 1 in S. aureus-induced hBD-3 gene expression.
      Combined, these studies indicate a role for TLR2 signaling and MAPK activation in
      the upregulation of hBD-3 and demonstrate the innate immune capacity of skin
      keratinocytes under conditions of S. aureus challenge to enhance the local
      expression of this antistaphylococcal peptide antibiotic.

PMID- 16954398
TI  - Acquisition of avian pathogenic Escherichia coli plasmids by a commensal E. coli
      isolate enhances its abilities to kill chicken embryos, grow in human urine, and
      colonize the murine kidney.
AB  - We have found an avian pathogenic Escherichia coli (APEC) plasmid, pAPEC-O2-ColV,
      which contains many of the genes associated with APEC virulence and also shows
      similarity in content to a plasmid and pathogenicity island of human
      uropathogenic E. coli (UPEC). To test the possible role of this plasmid in
      virulence, it was transferred by conjugation along with a large R plasmid, pAPEC
      O2-R, into a commensal avian E. coli strain. The transconjugant was compared to
      recipient strain NC, UPEC strain HE300, and donor strain APEC O2 using various
      assays, including lethality for chicken embryos, growth in human urine, and
      ability to cause urinary tract infection in mice. The transconjugant killed
      significantly more chicken embryos than did the recipient. In human urine, APEC
      O2 grew at a rate equivalent to that of UPEC strain HE300, and the transconjugant
      showed significantly increased growth compared to the recipient. The
      transconjugant also significantly outcompeted the recipient in colonization of
      the murine kidney. These findings suggest that APEC plasmids, such as pAPEC-O2
      ColV, contribute to the pathogenesis of avian colibacillosis. Moreover, since
      avian E. coli and their plasmids may be transmitted to humans, evaluation of APEC
      plasmids as possible reservoirs of urovirulence genes for human UPEC may be
      warranted.

PMID- 16954399
TI  - Evidence that tight junctions are disrupted due to intimate bacterial contact and
      not inflammation during attaching and effacing pathogen infection in vivo.
AB  - It is widely accepted that tight junctions are altered during infections by
      attaching and effacing (A/E) pathogens. These disruptions have been demonstrated
      both in vitro and more recently in vivo. For in vivo experiments, the murine
      model of A/E infection with Citrobacter rodentium is the animal model of choice.
      In addition to effects on tight junctions, these bacteria also colonize the colon
      at high levels, efface colonocyte microvilli, and cause hyperplasia and
      inflammation. Although we have recently demonstrated that tight junctions are
      disrupted by C. rodentium, the issue of direct effects of bacteria on epithelial
      cell junctions versus the indirect effects of inflammation still remains to be
      clarified. Here, we demonstrate that during the C. rodentium infections,
      inflammation plays no discernible role in the alteration of tight junctions. The
      distribution of the tight junction proteins, claudin-1, -3, and -5, are
      unaffected in inflamed colon, and junctions appear morphologically unaltered when
      viewed by electron microscopy. Additionally, tracer molecules are not capable of
      penetrating the inflamed colonic epithelium of infected mice that have cleared
      the bacteria. Finally, infected colonocytes from mice exposed to C. rodentium for
      14 days, which have high levels of bacterial attachment to colonocytes as well as
      inflammation, have characteristic, altered claudin localization whereas cells
      adjacent to infected colonocytes retain their normal claudin distribution. We
      conclude that inflammation plays no discernible role in tight junction alteration
      during A/E pathogenesis and that tight junction disruption in vivo appears
      dependent only on the direct intimate attachment of the pathogenic bacteria to
      the cells.

PMID- 16954400
TI  - A newly identified leptospiral adhesin mediates attachment to laminin.
AB  - Pathogenic leptospires have the ability to survive and disseminate to multiple
      organs after penetrating the host. Several pathogens, including spirochetes, have
      been shown to express surface proteins that interact with the extracellular
      matrix (ECM). This adhesin-mediated binding process seems to be a crucial step in
      the colonization of host tissues. This study examined the interaction of putative
      leptospiral outer membrane proteins with laminin, collagen type I, collagen type
      IV, cellular fibronectin, and plasma fibronectin. Six predicted coding sequences
      selected from the Leptospira interrogans serovar Copenhageni genome were cloned,
      and proteins were expressed, purified by metal affinity chromatography, and
      characterized by circular dichroism spectroscopy. Their capacity to mediate
      attachment to ECM components was evaluated by binding assays. We have identified
      a leptospiral protein encoded by LIC12906, named Lsa24 (leptospiral surface
      adhesin; 24 kDa) that binds strongly to laminin. Attachment of Lsa24 to laminin
      was specific, dose dependent, and saturable. Laminin oxidation by sodium
      metaperiodate reduced the protein-laminin interaction in a concentration
      dependent manner, indicating that laminin sugar moieties are crucial for this
      interaction. Triton X-114-solubilized extract of L. interrogans and phase
      partitioning showed that Lsa24 was exclusively in the detergent phase, indicating
      that it is a component of the leptospiral membrane. Moreover, Lsa24 partially
      inhibited leptospiral adherence to immobilized laminin. This newly identified
      membrane protein may play a role in mediating adhesion of L. interrogans to the
      host. To our knowledge, this is the first leptospiral adhesin with laminin
      binding properties reported to date.

PMID- 16954401
TI  - Mice naturally resistant to Yersinia pestis Delta pgm strains commonly used in
      pathogenicity studies.
AB  - We report that females of some substrains of inbred mouse strain 129 are
      resistant to systemic plague due to conditionally virulent Deltapgm strains of
      Yersinia pestis; however, fully virulent Y. pestis is not attenuated in these
      mice. Therefore, these mice offer a powerful system in which to map in parallel
      host resistance traits and opposing bacterial virulence properties for plague.

PMID- 16954402
TI  - Hierarchy of iron uptake systems: Yfu and Yiu are functional in Yersinia pestis.
AB  - In addition to the yersiniabactin (Ybt) siderophore-dependent system, two
      inorganic iron ABC transport systems of Yersinia pestis, Yfe and Yfu, have been
      characterized. Here we show that the Yfu system functions in Y. pestis: a Ybt-
      Yfe- Yfu- mutant exhibited a greater growth defect under iron-deficient
      conditions than its Ybt- Yfe- parental strain. We also demonstrate that another
      putative Y. pestis iron uptake system, Yiu, which potentially encodes an outer
      membrane receptor, YiuR, and an ABC iron transport cassette, YiuABC, is
      functional. The cloned yiuABC operon restored growth of an enterobactin-deficient
      mutant Escherichia coli strain, 1017, under iron-chelated conditions. Iron uptake
      by the Yiu system in Y. pestis was demonstrated only when the Ybt, Yfe, and Yfu
      systems were mutated. Using a yiuA::lacZ fusion, we show that the yiuABC promoter
      is repressed by iron through Fur. A mouse model of bubonic plague failed to show
      a significant role for the Yiu system in the disease process. These results
      demonstrate that two additional iron transporters are functional in Y. pestis and
      indicate that there is a hierarchy of iron transporters, with Ybt being most
      effective and Yiu being the least effective of those systems which have been
      characterized.

PMID- 16954403
TI  - Random mutagenesis of Helicobacter pylori vacA to identify amino acids essential
      for vacuolating cytotoxic activity.
AB  - VacA is a secreted toxin that plays a role in Helicobacter pylori colonization of
      the stomach and may contribute to the pathogenesis of peptic ulcer disease and
      gastric cancer. In this study, we analyzed a library of plasmids expressing
      randomly mutated forms of recombinant VacA and identified 10 mutant VacA proteins
      that lacked vacuolating cytotoxic activity when added to HeLa cells. The
      mutations included six single amino acid substitutions within an amino-terminal
      hydrophobic region and four substitutions outside the amino-terminal hydrophobic
      region. All 10 mutations mapped within the p33 domain of VacA. By introducing
      mutations into the H. pylori chromosomal vacA gene, we showed that secreted
      mutant toxins containing V21L, S25L, G121R, or S246L mutations bound to cells and
      were internalized but had defects in vacuolating activity. In planar lipid
      bilayer and membrane depolarization assays, VacA proteins containing V21L and
      S25L mutations were defective in formation of anion-selective membrane channels,
      whereas proteins containing G121R or S246L mutations retained channel-forming
      capacity. These are the first point mutations outside the amino-terminal
      hydrophobic region that are known to abrogate vacuolating toxin activity. In
      addition, these are the first examples of mutant VacA proteins that have defects
      in vacuolating activity despite exhibiting channel activities similar to those of
      wild-type VacA.

PMID- 16954404
TI  - The dbpBA locus of Borrelia burgdorferi is not essential for infection of mice.
AB  - The Lyme disease spirochete Borrelia burgdorferi expresses a broad array of
      adhesive molecules, including the decorin-binding proteins A and B (DbpA and
      DbpB), which are believed to play important roles in mammalian infection. The
      dbpBA locus was deleted; resulting mutants were able to infect both
      immunodeficient and immunocompetent mice, indicating that neither DbpA nor DbpB
      is essential for the infection of mammals, although the DbpAB deficiency may
      significantly attenuate infectivity potential.

PMID- 16954405
TI  - Amino acid residues within enterohemorrhagic Escherichia coli O157:H7 Tir
      involved in phosphorylation, alpha-actinin recruitment, and Nck-independent
      pedestal formation.
AB  - Enterohemorrhagic Escherichia coli (EHEC) O157:H7 and enteropathogenic E. coli
      (EPEC) adherence to epithelial cells results in the formation of actin pedestals.
      Pedestal formation requires the bacterial protein Tir, which is inserted into the
      epithelial cell plasma membrane by the type III secretion system. EPEC and EHEC
      use different Tir-based mechanisms for pedestal formation, and the EPEC Tir
      residues required have been well described. In contrast, little is known about
      the regions of EHEC O157:H7 Tir that are essential for pedestal formation.
      Additionally, EHEC O157:H7 Tir is serine/threonine phosphorylated, although the
      residues involved and their role in pedestal formation are not known. In this
      study, we describe two regions within the carboxy terminus of EHEC O157:H7 Tir
      that are required for phosphorylation and pedestal formation. Serines 436 and 437
      are substrates for protein kinase A phosphorylation, although this is not
      required to form pedestals. Using a series of internal deletion mutants, we found
      that amino acids 454 to 463 are required for efficient pedestal formation.
      Deleting this region resulted in a significant decrease in the recruitment of
      both filamentous actin and the actin binding protein alpha-actinin. As alpha
      actinin binds directly to the EHEC O157:H7 amino terminus, these data suggest
      that its recruitment is dependent on pedestal formation.

PMID- 16954406
TI  - Identification of a human ortholog of the mouse Dcpp gene locus, encoding a novel
      member of the CSP-1/Dcpp salivary protein family.
AB  - Salivary fluid, the collective product of numerous major and minor salivary
      glands, contains a range of secretory proteins that play key defensive,
      digestive, and gustatory roles in the oral cavity. To understand the distinct
      protein "signature" contributed by individual salivary glands to salivary
      secretions, we studied a family of proteins shown by in vitro mRNA translation to
      be abundantly expressed in mouse sublingual glands. Molecular cloning, Southern
      blotting, and restriction fragment length polymorphism analyses showed these to
      represent one known and two novel members of the common salivary protein (CSP
      1)/Demilune cell and parotid protein (Dcpp) salivary protein family, the genes
      for which are closely linked in the T-complex region of mouse chromosome 17.
      Bioinformatic analysis identified a putative human CSP-1/Dcpp ortholog, HRPE773,
      expressed predominantly in human salivary tissue, that shows 31% amino acid
      identity and 45% amino acid similarity to the mouse Dcpp query sequence. The
      corresponding human gene displays a similar structure to the mouse Dcpp genes and
      is located on human chromosome 16 in a region known to be syntenic with the T
      complex region of mouse chromosome 17. The predicted mouse and human proteins
      both display classical NH(2)-terminal signal sequences, putative jacalin-related
      lectin domains, and potential N-linked glycosylation sites, suggesting secretion
      via sublingual saliva into the oral cavity where they may display antimicrobial
      activity or provide a defensive coating to enamel. Identification of a human CSP
      1/Dcpp ortholog therefore provides a key tool for investigation of salivary
      protein function in human oral health and disease.

PMID- 16954407
TI  - Gene expression profiling in the neuroendocrine brain of male goldfish (Carassius
      auratus) exposed to 17alpha-ethinylestradiol.
AB  - 17-alpha ethinylestradiol (EE2), a pharmaceutical estrogen, is detectable in
      water systems worldwide. Although studies report on the effects of xenoestrogens
      in tissues such as liver and gonad, few studies to date have investigated the
      effects of EE2 in the vertebrate brain at a large scale. The purpose of this
      study was to develop a goldfish brain-enriched cDNA array and use this in
      conjunction with a mixed tissue carp microarray to study the genomic response to
      EE2 in the brain. Gonad-intact male goldfish were exposed to nominal
      concentrations of 0.1 nM (29.6 ng/l) and 1.0 nM (296 ng/l) EE2 for 15 days. Male
      goldfish treated with the higher dose of EE2 had significantly smaller gonads
      compared with controls. Males also had a significantly reduced level of
      circulating testosterone (T) and 17beta-estradiol (E2) in both treatment groups.
      Candidate genes identified by microarray analysis fall into functional categories
      that include neuropeptides, cell metabolism, and transcription/translation
      factors. Differentially expressed genes verified by real-time RT-PCR included
      brain aromatase, secretogranin-III, and interferon-related developmental
      regulator 1. Our results suggest that the expression of genes in the sexually
      mature adult brain appears to be resistant to low EE2 exposure but is affected
      significantly at higher doses of EE2. This study demonstrates that microarray
      technology is a useful tool to study the effects of endocrine disrupting
      chemicals on neuroendocrine function and suggest that exposure to EE2 may have
      significant effects on localized E2 synthesis in the brain by affecting
      transcription of brain aromatase.

PMID- 16954408
TI  - Multiple mechanisms limit the duration of wakefulness in Drosophila brain.
AB  - The functions of sleep and what controls it remain unanswered biological
      questions. According to the two-process model, a circadian process and a
      homeostatic process interact to regulate sleep. While progress has been made in
      understanding the molecular and cellular functions of the circadian process, the
      mechanisms of the homeostatic process remain undiscovered. We use the recently
      established sleep model system organism Drosophila melanogaster to examine
      dynamic changes in gene expression during sleep and during prolonged wakefulness
      in the brain. Our experimental design controls for circadian processes by killing
      animals at three matched time points from the beginning of the consolidated rest
      period [Zeitgeber time (ZT) 14)] under two conditions, sleep deprived and
      spontaneously sleeping. Using ANOVA at a false discovery rate of 5%, we have
      identified 252 genes that were differentially expressed between sleep-deprived
      and control groups in the Drosophila brain. Using linear trends analysis, we have
      separated the significant differentially expressed genes into nine temporal
      expression patterns relative to a common anchor point (ZT 14). The most common
      expression pattern is a decrease during extended wakefulness but no change during
      spontaneous sleep (n = 114). Genes in this category were involved in protein
      production (n = 47), calcium homeostasis, and membrane excitability (n = 5).
      Multiple mechanisms, therefore, act to limit wakefulness. In addition, by
      studying the effects of the mechanical stimulus used in our deprivation studies
      during the period when the animals are predominantly active, we provide evidence
      for a previously unappreciated role for the Drosophila immune system in the brain
      response to stress.

PMID- 16954409
TI  - Comparison of different gonadotrophin preparations in intrauterine insemination
      cycles for the treatment of unexplained infertility: a prospective, randomized
      study.
AB  - BACKGROUND: A comparison of the effectiveness of different gonadotrophin
      preparations in intrauterine insemination (IUI) cycles for patients with
      unexplained infertility was performed. METHODS: Two hundred and forty-one
      patients were prospectively randomized using computer-generated random numbers
      into three groups: 81 in the Follitropin alpha (Group I), 80 in the urinary FSH
      (uFSH) (Group II) and 80 in the hMG (Group III). The primary outcome was clinical
      pregnancy rate with duration of stimulation, total gonadotrophin dose, number of
      dominant follicles, clinical pregnancy rate, multiple pregnancy, miscarriage rate
      and ovarian hyperstimulation syndrome (OHSS) rate being secondary outcomes.
      RESULTS: Clinical pregnancy rate was significantly higher in the rFSH group
      (25.9% in Follitropin alpha, 13.8% in uFSH and 12.5% in HMG groups; P = 0.04).
      There was no significant difference in terms of duration of stimulation, but mean
      FSH dose consumed per cycle was significantly lower in the recombinant FSH (rFSH)
      group compared with others (825 IU in Follitropin alpha, 1107 IU in uFSH and 1197
      IU in HMG groups; P = 0.001). The number of follicles > or =16 mm diameter was
      significantly higher in the rFSH group compared with the uFSH and HMG groups (2.6
      in Follitropin alpha, 1.3 in uFSH and 1.4 in HMG groups; P = 0.001). CONCLUSION:
      rFSH may result in a better outcome in IUI cycles for unexplained infertility.

PMID- 16954410
TI  - Serum anti-Mullerian hormone expression in women with premature ovarian failure.
AB  - BACKGROUND: Premature ovarian failure (POF) is generally irreversible. However,
      developing follicles up to the antral stage are reported in POF and anti
      Mullerian hormone (AMH) might be a good indicator of follicular presence. This
      study analysed serum AMH, ovarian histology and AMH immunoexpression in POF
      patients. METHODS: A cross-sectional study of 48 POF patients in an Endocrinology
      Department setting. Patients had an ovarian biopsy simultaneously with serum AMH
      sampling and/or ovarian AMH immunostaining. RESULTS: Mean serum AMH was 1.04 +/-
      1.66 ng/ml. Serum AMH was significantly higher in women with 15 or more follicles
      at ovarian histology (P = 0.001). Comparison of ovarian AMH immunostaining from
      POF patients and 10 normal controls revealed a normal AMH expression in POF pre
      antral follicles, but a decreased expression at the early antral stages. Serum
      AMH was undetectable in 77% of the patients with 0-5 AMH immunopositive follicles
      and detectable in 100% of the patients with more than 15 AMH immunopositive
      follicles. CONCLUSIONS: AMH levels in POF patients could identify women with
      persistent follicles. The decrease of AMH immunoexpression in POF antral
      follicles could suggest a defect of antral development.

PMID- 16954411
TI  - A survey of dual-degree training opportunities at US dental schools.
AB  - The purpose of this article is to describe access to information for the dual
      degree dental scientist training programs (D.D.S.-D.M.D./Ph.D.) currently
      available for predoctoral students at U.S. dental schools. Given the ongoing
      shortage of dental faculty and the progressive emphasis on evidence-based
      dentistry, these programs will be instrumental in training future dental faculty.
      A comprehensive review of the institutional websites for all fifty-six U.S.
      dental schools was undertaken in January 2006. After identification of advertised
      dual-degree programs, a follow-up survey was sent to twenty-two dental schools
      that described the existence of a dual-degree dental scientist training program.
      The results of the survey and website review indicate that there are a number of
      programs in operation, but it is difficult to determine even basic features of
      these programs including curriculum structure, financial aid, and infrastructure
      support for students. Several current dental scientist trainee students were also
      contacted to discuss their programs in more detail. The insights derived from
      this investigation may assist dental school applicants, current predoctoral
      dental students, and administrators seeking to design or promote their existing
      dental scientist training programs.

PMID- 16954412
TI  - Increasing access to care with diversity.
AB  - While many factors contribute to lack of access to dental care along racial and
      ethnic lines, one of the most prominent factors is a lack of diversity among oral
      health professionals. Surveys and studies show that individuals in minority
      communities are more likely to seek treatment from people of their own racial or
      ethnic background and, in turn, that those caregivers are more likely to work in
      minority communities and have a desire to provide care to the underserved.
      Further studies show that increasing diversity in dental schools can help
      motivate all dental students, not just minorities, to provide care to the
      underserved after graduation. To increase diversity in the workforce, there must
      be an increase in diversity at dental schools. Admissions committees need to
      reanalyze standard admissions criteria to achieve the goal of building a diverse
      student body that is representative of the ethnic and cultural diversity of our
      nation. Increasing the diversity of our schools enhances the educational
      experience and increases the likelihood that dental school graduates will
      practice in ways that extend oral care services to all segments of society.

PMID- 16954413
TI  - The case for change in dental education.
AB  - This article introduces a series of white papers developed by the ADEA Commission
      on Change and Innovation (CCI) to explore the case for change in dental
      education. This preamble to the series argues that there is a compelling need for
      rethinking the approach to dental education in the United States. Three issues
      facing dental education are explored: 1) the challenging financial environment of
      higher education, making dental schools very expensive and tuition-intensive for
      universities to operate and producing high debt levels for students that limit
      access to education and restrict career choices; 2) the profession's apparent
      loss of vision for taking care of the oral health needs of all components of
      society and the resultant potential for marginalization of dentistry as a
      specialized health care service available only to the affluent; and 3) the nature
      of dental school education itself, which has been described as convoluted,
      expensive, and often deeply dissatisfying to its students.

PMID- 16954414
TI  - Educational strategies associated with development of problem-solving, critical
      thinking, and self-directed learning.
AB  - This article was developed for the Commission on Change and Innovation in Dental
      Education (CCI), established by the American Dental Education Association. CCI
      was created because numerous organizations within organized dentistry and the
      educational community have initiated studies or proposed modifications to the
      process of dental education, often working to achieve positive and desirable
      goals but without coordination or communication. The fundamental mission of CCI
      is to serve as a focal meeting place where dental educators and administrators,
      representatives from organized dentistry, the dental licensure community, the
      Commission on Dental Accreditation, the ADA Council on Dental Education and
      Licensure, and the Joint Commission on National Dental Examinations can meet and
      coordinate efforts to improve dental education and the nation's oral health. One
      of the objectives of the CCI is to provide guidance to dental schools related to
      curriculum design. In pursuit of that objective, this article summarizes the
      evidence related to this question: What are educational best practices for
      helping dental students acquire the capacity to function as an entry-level
      general dentist or to be a better candidate to begin advanced studies? Three
      issues are addressed, with special emphasis on the third: 1) What constitutes
      expertise, and when does an individual become an expert? 2) What are the
      differences between novice and expert thinking? and 3) What educational best
      practices can help our students acquire mental capacities associated with expert
      function, including critical thinking and self-directed learning? The purpose of
      this review is to provide a benchmark that faculty and academic planners can use
      to assess the degree to which their curricula include learning experiences
      associated with development of problem-solving, critical thinking, self-directed
      learning, and other cognitive skills necessary for dental school graduates to
      ultimately become expert performers as they develop professionally in the years
      after graduation.

PMID- 16954415
TI  - Identification of competencies for effective dental faculty.
AB  - A faculty of sufficient size and possessing the appropriate skills is critical to
      dental education. Faculty shortages have been identified, but little has been
      written about the skills and abilities necessary for dental faculty to be
      effective. This project identified consensus lists of competencies in the areas
      of teaching and research. A panel of dental education experts used a web-based
      Delphi method to refine competency lists. The final lists of competency
      statements were organized into foundational competencies that applied to all
      areas and several areas of major competencies that were defined by supporting
      competencies. The panel rated the importance of each competency statement for
      each of three dental faculty categories: 1) clinical teachers, 2) clinical
      scholars, and 3) research-intensive scholars. The identification of a consensus
      list of competency statements for effective dental faculty will facilitate the
      development of programs for faculty to attain and maintain these competencies.
      ADEA could play a coordinating role in this faculty development effort.

PMID- 16954416
TI  - Development and implementation of a comprehensive faculty development program in
      PBL core skills.
AB  - Large curricular changes associated with changes in teaching and learning methods
      should be accompanied by faculty development programs linked to the new pedagogy.
      This article describes a framework for the development and implementation of a
      program designed to assist faculty with the transition of the dental curriculum
      to a problem-based learning (PBL) pedagogy. A faculty committee created a PBL
      core skills program based on experiential, developmentally appropriate approaches
      that resulted in constructive and social learning opportunities for the faculty
      participants. Nearly 70 percent of faculty members have participated in the
      facilitation preparation workshops and contributed to the D.D.S. curriculum as
      small-group, inquiry-based learning facilitators. Faculty development programs
      geared toward acquisition of specific teaching skills and based on adult learning
      principles can be devised locally and result in increased participation in a new
      curriculum.

PMID- 16954417
TI  - Fluoride knowledge and prescription practices among dentists.
AB  - The purpose of this study was to assess dentists' knowledge about fluorides as
      well as their prescription practices. The study population consists of all
      general and pediatric dentists in Houston, and the sample consists of 360 general
      and forty-one pediatric dentists. Data were collected with a self-administered
      mail questionnaire, which consisted of thirteen open-ended and twenty-nine
      precoded items. After three mailings, the effective response rate was 46.4
      percent. Respondents had been in practice on an average of 18.9 +/-6.6 years; the
      majority were male. More than 75 percent of respondents believed fluoride level
      in drinking water is an important determinant of fluoride supplement
      prescription, and 29 percent felt the same about a patient's weight. The correct
      ages at which to begin (six months) and to discontinue (sixteen years) the
      fluoride supplements to children were identified by 14.7 and 14.9 percent of the
      respondents, respectively. Only 6.7 percent of those prescribing fluoride
      supplements routinely tested the fluoride level in the patient's drinking water.
      Even though pediatric and general dentists differed in certain items, the two
      groups did not differ significantly in prescribing fluorides (OR=2.4, 95%
      CI=0.94, 6.27). Deficiencies and ambiguity in respondents' fluorides knowledge as
      well as prescription practices indicated a need for educational interventions.

PMID- 16954418
TI  - The impact of quality assurance programming: a comparison of two canadian dental
      hygienist programs.
AB  - Quality assurance (QA) and continuing competence (CC) programs aim to ensure
      acceptable levels of health care provider competence, but it is unknown which
      program methods most successfully achieve this goal. The objectives of the study
      reported in this article were to compare two distinct QA/CC programs of Canadian
      dental hygienists and assess the impact of these two programs on practice
      behavior change, a proxy measure for quality. British Columbia (BC) and Ontario
      (ON) were compared because the former mandates continuing education (CE) time
      requirements. A two-group comparison survey design using a self-administered
      questionnaire was implemented in randomly selected samples from two
      jurisdictions. No statistical differences were found in total activity, change
      opportunities, or change implementation, but ON study subjects participated in
      significantly more activities that yielded change opportunities and more
      activities that generated appropriate change implementation, meaning positive and
      correct approaches to providing care, than BC dental hygienists. Both groups
      reported implementing change to a similarly high degree. The findings suggest
      that ON dental hygienists participated in more learning activities that had
      relevancy to their practice and learning needs than did BC subjects. The findings
      indicate that the QA program in ON may allow for greater efficiency in
      professional learning.

PMID- 16954419
TI  - Canadian dental students' perceptions of their learning environment and
      psychological functioning over time.
AB  - A cohort of dental students (N=28) at the University of Manitoba was followed
      throughout their entire dental education program to explore changes in their
      perceptions of the learning environment over time. Aspects of the
      students'psychological functioning, including common psychological symptoms, self
      esteem, and coping strategies, were also evaluated to assess changes in these
      factors over time. A battery of instruments consisting of the Learning
      Environment Survey (LES), the Symptom Questionnaire (SQ), the Ways of Coping
      Checklist (WCCL), and the State Self-Esteem Scale (SSES) was administered at the
      beginning, midpoint, and end of each academic year throughout the four-year
      dental education program. Results indicated that there was a minor positive
      recalibration of student perceptions in the areas of course relevance and
      opportunities for outside interests during the first months of year one. Apart
      from this, perceptions of dental school as a seldom-to-occasionally positive
      learning environment were maintained over the entire dental education program. In
      terms of psychological functioning over time, students reported decreases in
      their levels of problem-focused coping and self-esteem, increased use of
      avoidance and wishful thinking as coping strategies, and more anxiety,
      depression, and hostility at various points. Some implications of these findings
      for dental education are discussed.

PMID- 16954420
TI  - A snapshot of cultural competency education in US dental schools.
AB  - During the last decade, cultural competency has received a great deal of
      attention in health care and the literature of many fields, including education,
      social services, law, and health care. The dental education literature provides
      little information regarding status, strategies, or guiding principles of
      cultural competency education in U.S. dental schools. This study was an attempt
      to describe the status of cultural competency education in U.S. dental schools. A
      web-based thirty-question survey regarding cultural competency education
      coursework, teaching, course materials, and content was sent in 2005 to the
      assistant/associate deans for academic affairs at fifty-six U.S. dental schools,
      followed up by subsequent email messages. Thirty-four (61 percent) dental school
      officials responded to the survey. The majority of respondents (twenty-eight; 82
      percent) did not have a specific stand-alone cultural competency course, but
      indicated it was integrated into the curriculum. Recognition of local and
      national community diversity needs prompted course creation in most schools.
      Respondents at almost two-thirds of schools indicated that their impression of
      students' acceptance was positive. Teachers of cultural competency were primarily
      white female dentists. Few schools required faculty to have similar cultural
      competency or diversity training. Thirty-three of the thirty-four U.S. dental
      schools responding to this survey offer some form of coursework in cultural
      competency with little standardization and a variety of methods and strategies to
      teach dental students.

PMID- 16954421
TI  - Attitudes and awareness of final-year predoctoral dental and medical students to
      medical problems in dentistry.
AB  - An increasing proportion of the population is medically compromised. Dental and
      medical staff need to communicate and cooperate to afford these patients the best
      possible health care. In this study, the attitude towards and awareness of
      medical problems were examined in final-year predoctoral (undergraduate) dental
      and in final-year medical students. The results revealed that most dental
      students felt their knowledge of and training in medical problems in dentistry to
      be moderate to good. In contrast, most medical students thought both their
      knowledge and training in medical problems in dentistry to be only poor to
      moderate. Dental students rated the importance of medical problems in dentistry
      higher than did medical students.

PMID- 16954422
TI  - Characteristics and study motivation of clinical dental students in Nigerian
      universities.
AB  - A cross-sectional study of a cohort of 197 clinical dental students in the four
      accredited dental schools in Nigeria was conducted to determine the
      sociodemographic characteristics of these dental students and their motives for
      the choice of dentistry. The results indicate that the number of female dental
      students in Nigeria is increasing, which reflects a trend well established in
      virtually all other nations. The vast majority of Nigerian dental students (97
      percent) qualified for school based on their performance on the University
      Matriculation Examination. About one-third, 32.5 percent, indicated that
      dentistry was their first choice for a career. This choice was greatly influenced
      by family in 50 percent of this group of students. There were several factors
      that strongly influenced career choice among students who indicated that
      dentistry was their first choice: interest, prestige, good employment opportunity
      abroad, and regular work hours. The need to go into a prestigious and financially
      lucrative profession similar to medicine were the commonest reasons identified by
      the group of students for whom dentistry was not the first career choice. The
      motives for choosing dentistry as a career in this group of students seem to
      relate to an image of dentistry as a vehicle for the achievement of personal
      goals. It is recommended that high school students be encouraged to see dentistry
      first hand. This is because in countries such as Nigeria it is not unusual for a
      potential dental student to have never visited the dentist.

PMID- 16954423
TI  - Combinatorial androgen receptor targeted therapy for prostate cancer.
AB  - Prostatic carcinogenesis is associated with changes in the androgen receptor (AR)
      axis converting it from a paracrine dependence upon stromal signaling to an
      autocrine-initiated signaling for proliferation and survival of prostatic cancer
      cells. This malignant conversion is due to gain of function changes in which the
      AR activates novel genomic (i.e. transcriptional) and non-genomic signaling
      pathways, which are not present in normal prostate epithelial cells. During
      further progression, additional molecular changes occur which allow these unique
      malignancy-dependent AR signaling pathways to be activated even in the low
      androgen ligand environment present following androgen ablation therapy. These
      signaling pathways are the result of partnering the AR with a series of other
      genomic (e.g. transcriptional co-activators) or non-genomic (e.g. steroid
      receptor co-activator (Src) kinase) signaling molecules. Thus, a combinatorial
      androgen receptor targeted therapy (termed CART therapy) inhibiting several
      points in the AR signaling cascade is needed to prevent the approximately 30,000
      US males per year dying subsequent to failure of standard androgen ablation
      therapy. To develop such CART therapy, a series of agents targeted at specific
      points in the AR cascade should be used in combination with standard androgen
      ablative therapy to define the fewest number of agents needed to produce the
      maximal therapeutic anti-prostate cancer effect. As an initial approach for
      developing such CART therapy, a variety of new agents could be combined with
      luteinizing hormone-releasing hormone analogs. These include: (1) 5alpha
      reductase inhibitors to inhibit the conversion of testosterone to the more potent
      androgen, dihydrotestosterone; (2) geldanamycin analogs to downregulate AR
      protein in prostate cancer cells, (3) 'bulky' steroid analogs, which can bind to
      AR and prevent its partnering with other co-activators/signaling molecules, and
      (4) small molecule kinase inhibitors to inhibit MEK, which is activated as part
      of the malignant AR signaling cascade.

PMID- 16954424
TI  - Sex-steroid regulation of vascular endothelial growth factor in breast cancer.
AB  - Angiogenesis is a key event, which occurs in both normal and pathological
      expansion of tissues and provides the nourishment necessary for growth. The role
      of angiogenic growth factors in breast pathology is rapidly gaining recognition
      since scientists and clinicians realized that these factors could function as
      molecular targets event 550 209822 for controlling tumor expansion. Vascular
      endothelial growth factor (VEGF) is a key regulator of angiogenesis. Although
      significant advances have been made in understanding the sex-steroid-dependent
      regulation of this key factor, the role of VEGF in controlling breast tumors is
      not well understood. In this review, I discuss recent studies describing the role
      of the female sex steroids estrogens and progestins in the regulation of VEGF in
      breast cancer cells. Furthermore, I present a summary of recent studies from
      other biological systems (mainly focused on tumor biology) directed towards
      providing us with a better understanding of the regulation of classical VEGF and
      VEGF receptors. I propose that by extending such studies we will gain deeper
      insights into how we might combat the progression of breast cancer by controlling
      hormone-dependent angiogenesis within tumor tissue. I believe that information
      gained from such studies will permit us to target angiogenic growth factors and
      their initiated signal transduction pathways in a more precise and selective
      manner, and thereby to control the formation of new blood vessels that fuel the
      rapid growth of breast tumors. Finally, it is my hope that the concepts discussed
      here will help elucidate molecular targets in the hormone-dependent angiogenesis
      pathway that will ultimately allow us to overcome anti-hormone resistance and to
      provide insights into how we might pursue the concept of chemoprevention by
      considering 'angioprevention' as the end point.

PMID- 16954425
TI  - Pure oestrogen antagonists for the treatment of advanced breast cancer.
AB  - For more than 30 years, tamoxifen has been the drug of choice in treating
      patients with oestrogen receptor (ER)-positive breast tumours. However, research
      has endeavoured to develop agents that match and improve the clinical efficacy of
      tamoxifen, but lack its partial agonist effects. The first 'pure' oestrogen
      antagonist was developed in 1987; from this, an even more potent derivative was
      developed for clinical use, known as fulvestrant (ICI 182,780, 'Faslodex').
      Mechanistic studies have shown that fulvestrant possesses high ER-binding
      affinity and has multiple effects on ER signalling: it blocks dimerisation and
      nuclear localisation of the ER, reduces cellular levels of ER and blocks ER
      mediated gene transcription. Unlike anti-oestrogens chemically related to
      tamoxifen, fulvestrant also helps circumvent resistance to tamoxifen. There are
      extensive data to support the lack of partial agonist effects of fulvestrant and,
      importantly, its lack of cross-resistance with tamoxifen. In phase III studies in
      patients with locally advanced or metastatic breast cancer, fulvestrant was at
      least as effective as anastrozole in patients with tamoxifen-resistant tumours,
      was effective in the first-line setting and was also well tolerated. These data
      are supported by experience from the compassionate use of fulvestrant in more
      heavily pretreated patients. Further studies are now underway to determine the
      best strategy for sequencing oestrogen endocrine therapies and to optimise dosing
      regimens offulvestrant. At present, and for the foreseeable future, fulvestrant
      is the only oestrogen antagonist with no agonistic effects licensed for the
      treatment of advanced breast cancer in postmenopausal women. Other similar
      oestrogen antagonists are undergoing research and development, with a few
      currently being evaluated in phase II trials.

PMID- 16954426
TI  - Pituitary tumours: findings from whole genome analyses.
AB  - Pituitary tumours are common intracranial neoplasms that cause significant
      morbidity through mass effects and/or the inappropriate secretion of pituitary
      hormones. Despite a considerable literature detailing potential pathogenic
      changes in these tumours, their aetiology remains largely unresolved. Recent
      studies have employed genome-wide profiling towards the identification of novel
      genes and pathways that are inappropriately expressed or regulated in this tumour
      type. The techniques employed vary in their complexity and interpretation;
      however, many of the findings from these types of studies have identified novel
      genes with potential and, in some cases, proven roles in pituitary tumorigenesis.
      These studies include comparative genomic hybridization, whole genome-wide
      allelotyping and methodologies for identification of novel genes associated with
      epigenetic silencing. In addition, differential display methodologies have been
      instrumental in the identification of transcripts inappropriately expressed
      including, pituitary tumour transforming gene, growth arrest and DNA damage
      inducible protein (GADD)45gamma and a maternal expressed gene 3 isoform, which in
      some cases have proven roles in pituitary tumorigenesis. Although few studies of
      whole genome transcript analysis, as determined by microarray or gene-chip
      technologies, are reported, these studies of human pituitary, in some cases
      combined with proteomics, are yielding useful data. In addition, these types of
      investigation have been applied to several animal models of pituitary
      tumorigenesis, and in these cases novel genes are highlighted as showing
      significant change. The identification of the initiating events responsible for
      the transformation of a normal pituitary cell into one with unrestrained
      proliferative capacity has so far eluded us. No doubt, these new technologies
      allowing an essentially unbiased genome-wide analysis, perhaps in combination
      with animal models that display a preceding hyperplasia, will allow us to
      identify genes critical to tumour evolution and progression.

PMID- 16954427
TI  - Progesterone metabolites in breast cancer.
AB  - In the 70 years since progesterone (P) was identified in corpus luteum extracts,
      its metabolism has been examined extensively in many tissues and cell lines from
      numerous species. In addition to the reproductive tissues and adrenals, every
      other tissue that has been investigated appears to have one or more P
      metabolizing enzyme, each of which is specific for a particular site on the P
      molecule. In the past, the actions of the P metabolizing enzymes generally have
      been equated to a means of reducing the P concentration in the tissue
      microenvironment, and the products have been dismissed as inactive waste
      metabolites. In human breast tissues and cell lines, the following P-metabolizing
      enzymes have been identified: 5alpha-reductase, 3alpha-hydroxysteroid
      oxidoreductase (3alpha-HSO), 3beta-HSO, 20alpha-HSO, and 6alpha-hydroxylase.
      Rather than providing diverse pathways for inactivating and controlling the
      concentration of P in breast tissue microenvironments, it is proposed that the
      enzymes act directly on P to produce two types of autocrines/paracrines with
      opposing regulatory roles in breast cancer. Evidence is reviewed which shows that
      P is directly converted to the 4-pregnenes, 3alpha-hydroxy-4-pregnen-20-one
      (3alpha-dihydroprogesterone; 3alphaHP) and 20alpha-dihydroprogesterone
      (20alphaHP), by the actions of 3alpha-HSO and 20alpha-HSO respectively and to the
      5alpha-pregnane, 5alpha-pregnane-3,20-dione(5alpha-dihydroprogesterone; 5alphaP),
      by the irreversible action of 5alpha-reductase. In vitro studies on a number of
      breast cell lines indicate that 3alphaHP promotes normalcy by downregulating cell
      proliferation and detachment, whereas 5alphaP promotes mitogenesis and metastasis
      by stimulating cell proliferation and detachment. The hormones bind to novel,
      separate, and specific plasma membrane-based receptors and influence opposing
      actions on mitosis, apoptosis, and cytoskeletal and adhesion plaque molecules via
      cell signaling pathways. In normal tissue, the ratio of 4-pregnenes:5alpha
      pregnanes is high because of high P 3alpha- and 20alpha-HSO activities/expression
      and low P 5alpha-reductase activity/expression. In breast tumor tissue and
      tumorigenic cell lines, the ratio is reversed in favor of the 5alpha-pregnanes
      because of altered P-metabolizing enzyme activities/expression. The evidence
      suggests that the promotion of breast cancer is related to changes in in situ
      concentrations of cancer-inhibiting and -promoting P metabolites. Current
      estrogen-based theories and therapies apply to only a fraction of all breast
      cancers; the majority (about two-thirds) of breast cancer cases are estrogen
      insensitive and have lacked endocrine explanations. As the P metabolites, 5alphaP
      and 3alphaHP, have been shown to act with equal efficacy on all breast cell lines
      tested, regardless of their tumorigenicity, estrogen sensitivity, and estrogen
      receptor/progesterone receptor status, it is proposed that they offer a new
      hormonal basis for all forms of breast cancer. New diagnostic and therapeutic
      possibilities for breast cancer progression, control, regression, and prevention
      are suggested.

PMID- 16954428
TI  - Hypoxia-inducible factor-1 in human breast and prostate cancer.
AB  - The tumor microenvironment is best characterized as a fluctuation of hypoxia and
      nutrient deprivation, which leads to epigenetic and genetic adaptation of clones
      and increased invasiveness and metastasis. In turn, these hypoxic adaptations
      make the tumors more difficult to treat and confer increased resistance to
      current therapies. Part of this adaptation is the regulation of gene products in
      response to hypoxia. Many of these hypoxia-regulated genes are mediated by the
      hypoxia-inducible factor 1 (HIF-1) complex, which is composed of a heterodimer
      pair of HIF-1alpha and HIF-1beta. This heterodimer binds to the promoter of
      hypoxia-responsive genes, while interacting with other transcription factors,
      such as p300, signal and transducer of transcription 3, and Redox effector factor
      1/apurinic/apyrimidinic endonuclease. HIF-1alpha levels itself can be regulated
      by hypoxia transcriptionally and post-translationally through ubiquitination; but
      the magnitude of the response is modulated by several other pathways, including
      free radicals that affect crosstalk with HIF-1alpha/HIF-1beta transcriptional
      activities. HIF-1alpha has emerged as an important transcription factor in breast
      cancer and prostate cancer biology, and is expressed in the early stages of
      mammary and prostate carcinogenesis. Its expression is correlated with diagnostic
      and prognostic indicators for early relapse and metastatic disease, thus making
      HIF-1alpha a potential prognostic biomarker in proteomic assessments of breast
      and prostate cancers. The importance of HIF-1alpha in tumor progression makes it
      a logical target for chemoprevention strategies in patients at higher genetic
      risk of breast and prostate cancer with Cox 2 inhibitors or 2-methoxyestradiol,
      as well as a target for new approaches to inhibiting angiogenesis. The crosstalk
      between estrogen signaling pathways and HIF-1alpha is still not fully defined in
      breast cancer, but downstream estrogen receptor signaling may be a candidate for
      estrogen modulation of HIF-1alpha levels. In prostate cancer, androgens
      upregulate HIF-1alpha through androgen-regulated autocrine receptor tyrosine
      kinase receptor signaling. This review will put into perspective the role of HIF
      1alpha in endocrine oncology and present new data on HIF-1alpha signaling and the
      potential for targeted therapies, including combinatory hormonal therapies.

PMID- 16954429
TI  - Mechanisms of action of novel agents for prostate cancer chemoprevention.
AB  - Despite advances in the understanding of prostate cancer (PCa) growth and
      development, it is still the leading incidence of cases and the second leading
      cause of mortality due to cancer in men. The problem of early diagnosis
      compounded with the emergence of androgen independence during commonly used anti
      androgen therapy of PCa, have been discouraging for optimal therapeutic response.
      Recently, many chemopreventive agents, including silibinin, inositol
      hexaphosphate, decursin, apigenin, acacetin, grape seed extract, curcumin, and
      epigallocatechin-3 gallate have been identified in laboratory studies, which
      could be useful in the management of PCa. In vivo pre-clinical studies have
      indicated chemopreventive effect of many such agents in PCa xenograft and
      transgenic mouse models. The molecular targets of these agents include cell
      signaling, cell-cycle regulators, and survival/apoptotic molecules, which are
      implicated in uncontrolled PCa growth and progression. Furthermore, angiogenic
      and metastatic targets, including vascular endothelial growth factor, hypoxia
      inducing factor-1alpha, matrix metalloproteinase, and urokinase-type plasminogen
      activator are also modulated by many chemopreventive agents to suppress the
      growth and invasive potential of PCa. This review focuses on novel PCa
      chemopreventive observations in laboratory studies, which could provide the
      rationale for the prospective use of chemopreventive agents in translational
      studies.

PMID- 16954430
TI  - Immunesurveillance by dendritic cells: potential implication for immunotherapy of
      endocrine cancers.
AB  - Dendritic cells (DCs) are highly efficient antigen-presenting cells in the immune
      system with the potential to regulate the system and induce a cytotoxic T-cell
      response. As a proof of principle, a multitude of animal and human studies has
      demonstrated that immunization with antigen-loaded DCs may lead to anti-tumour
      immune responses with tumour regression and rejection of cancer. The
      identification of tumour antigens that can be recognized by T lymphocytes has
      facilitated the development of new protocols and enabled immunologists to monitor
      immune responses. However, to date, long-term clinical effects on larger numbers
      of cancer patients are missing, and there is no generally accepted DC generation
      or activation protocol. This review will focus on the most important findings on
      the role of DCs within the immune system and how to generate and activate these
      cells in order to induce cytotoxic immunity in non-endocrine and endocrine
      malignancies. Recently, we and other researchers reported on DC vaccinations in
      patients with endocrine malignancies mainly in metastasized medullary thyroid
      carcinoma resulting in tumour-specific immunity and partial clinical responses in
      some cases. Based on these and other in vitro data, new DC vaccination protocols
      for the treatment of patients with endocrine tumours have now been conducted.

PMID- 16954431
TI  - Enhancement of sodium/iodide symporter expression in thyroid and breast cancer.
AB  - The sodium/iodide symporter (NIS) mediates iodide uptake in the thyroid gland and
      lactating breast. NIS mRNA and protein expression are detected in most thyroid
      cancer specimens, although functional iodide uptake is usually reduced resulting
      in the characteristic finding of a 'cold' or non-functioning lesion on a
      radioiodine image. Iodide uptake after thyroid stimulating hormone (TSH)
      stimulation, however, is sufficient in most differentiated thyroid cancer to
      utilize beta-emitting radioactive iodide for the treatment of residual and
      metastatic disease. Elevated serum TSH, achieved by thyroid hormone withdrawal in
      athyreotic patients or after recombinant human thyrotropin administration,
      directly stimulates NIS gene expression and/or NIS trafficking to the plasma
      membrane, increasing radioiodide uptake. Approximately 10-20% differentiated
      thyroid cancers, however, do not express the NIS gene despite TSH stimulation.
      These tumors are generally associated with a poor prognosis. Reduced NIS gene
      expression in thyroid cancer is likely due in part, to impaired trans-activation
      at the proximal promoter and/or the upstream enhancer. Basal NIS gene expression
      is detected in about 80% breast cancer specimens, but the fraction with
      functional iodide transport is relatively low. Lactogenic hormones and various
      nuclear hormone receptor ligands increase iodide uptake in breast cancer cells in
      vitro, but TSH has no effect. A wide range of 'differentiation' agents have been
      utilized to stimulate NIS expression in thyroid and breast cancer using in vitro
      and in vivo models, and a few have been used in clinical studies. Retinoic acid
      has been used to stimulate NIS expression in both thyroid and breast cancer.
      There are similarities and differences in NIS gene regulation and expression in
      thyroid and breast cancer. The various agents used to enhance NIS expression in
      thyroid and breast cancer will be reviewed with a focus on the mechanism of
      action. Agents that promote tumor differentiation, or directly stimulate NIS gene
      expression, may result in iodine concentration in 'scan-negative' thyroid cancer
      and some breast cancer.

PMID- 16954432
TI  - Novel concepts for the chemoprevention of breast cancer through aromatase
      inhibition.
AB  - Aromatase inhibitors (AIs) have a proven role in the treatment of early and
      metastatic breast cancer. The success of tamoxifen in reducing the relative risk
      of developing hormone-sensitive breast cancer in chemoprevention trials has been
      hampered by their long-term toxicity profile. AIs have the potential to further
      reduce rates of breast cancer in high-risk postmenopausal women. This article
      reviews the evidence to support the potential efficacy of AIs in the
      chemoprevention setting. It particularly focuses on a discussion of novel
      concepts of utilising AIs, so that they reduce breast cancer risk while
      minimising systemic toxicity, and highlights the importance of accurately
      developing risk prediction algorithms.

PMID- 16954433
TI  - Concomitant down-regulation of SPRY1 and SPRY2 in prostate carcinoma.
AB  - Sprouty proteins encoded by the SPRY genes act as modulators and feedback
      inhibitors of signalling by epidermal growth factor (EGF) and fibroblast growth
      factor (FGF). Overactivity of EGF and FGF signalling common in prostate cancer
      might therefore be exacerbated by Sprouty down-regulation. Indeed, down
      regulation of SPRY1 and SPRY2 expression has been independently reported. We
      found both genes modestly down-regulated by microarray expression analysis of
      microdissected prostate cancers and by quantitative RT-PCR in macrodissected
      specimens compared with benign tissues. Importantly, the decreases paralleled
      each other and expression levels of both genes were significantly lower in
      cancers that recurred within the average follow-up period of 32 months. In
      contrast to a previous report, no hypermethylation was found to accompany down
      regulation of SPRY2 in cancer tissues and cell lines. We additionally
      investigated the expression of an SPRY1 alternative transcript presumed to be
      specific for fetal tissues and found its expression moderately well correlated
      with expression of the standard transcript through diverse tissues and cell
      lines. The present study confirms and extends previous reports by demonstrating
      concomitant down-regulation and a significant association with recurrence of SPRY
      genes.

PMID- 16954434
TI  - Phosphorylation of ERalpha at serine 118 in primary breast cancer and in
      tamoxifen-resistant tumours is indicative of a complex role for ERalpha
      phosphorylation in breast cancer progression.
AB  - Oestrogen receptor-alpha (ERalpha) is an important prognostic marker in breast
      cancer and endocrine therapies are designed to inhibit or prevent ERalpha
      activity. In vitro studies have indicated that phosphorylation of ERalpha, in
      particular on serine 118 (S118), can result in activation in a ligand-independent
      manner, thereby potentially contributing to resistance to endocrine agents, such
      as tamoxifen and aromatase inhibitors. Here we report the immunohistochemistry
      (IHC) of S118 phosphorylation in 301 primary breast tumour biopsies.
      Surprisingly, this analysis shows that S118 phosphorylation is higher in more
      differentiated tumours, suggesting that phosphorylation at this site is
      associated with a good prognosis in patients not previously treated with
      endocrine agents. However, we also report that S118 phosphorylation was elevated
      in tumour biopsies taken from patients who had relapsed following tamoxifen
      treatment, when compared to pre-treatment biopsies. Taken together, these data
      are consistent with the view that S118 phosphorylation is a feature of normal
      ERalpha function and that increases in levels of phosphorylation at this site may
      play a key role in the emergence of endocrine resistance in breast cancer.

PMID- 16954435
TI  - Combination therapy for treating breast cancer using antiestrogen, ERA-923, and
      the mammalian target of rapamycin inhibitor, temsirolimus.
AB  - The effect of combinations of a mammalian target of rapamycin (mTOR) inhibitor,
      temsirolimus, and an estrogen receptor-alpha (ERalpha) antagonist, ERA-923, on
      breast carcinoma in culture and in a xenograft model has been studied. Phase III
      trials are underway using temsirolimus for several cancers. ERA-923 was studied
      in a phase I trial for tamoxifen refractory metastatic breast cancer and was
      shown to have good safety profiles. Combination of noninhibitory doses of
      temsirolimus with suboptimal doses of ERA-923 synergistically inhibited the
      growth of MCF-7 cells. Synergy was found across a wide range of doses and could
      also be achieved by combining temsirolimus with other antiestrogens such as
      raloxifene and 4-hydroxytamoxifen. In vivo combination of temsirolimus and ERA
      923 at certain doses and schedules completely inhibited tumor growth, while
      individual agents were only partially effective. Although the mechanism
      underlying the synergism remains to be understood, the results were associated
      with the ability of temsirolimus to block the transcriptional activity mediated
      by ERalpha as well as an increase in G1 arrest when it was combined with ERA-923.
      Results demonstrated for the first time that the combination of temsirolimus and
      a pure antiestrogen has excellent anticancer activity in preclinical models and,
      therefore, may have clinical use in treating hormone-dependent tumors.

PMID- 16954436
TI  - Proliferative responses to altered 17beta-hydroxysteroid dehydrogenase (17HSD)
      type 2 expression in human breast cancer cells are dependent on endogenous
      expression of 17HSD type 1 and the oestradiol receptors.
AB  - The primary source of oestrogen in premenopausal women is the ovary but, after
      menopause, oestrogen biosynthesis in peripheral tissue is the exclusive site of
      formation. An enzyme group that affects the availability of active oestrogens is
      the 17beta-hydroxysteroid dehydrogenase (17HSD) family. In breast cancer, 17HSD
      type 1 and type 2 have been mostly investigated and seem to be the principal
      17HSD enzymes involved thus far. The question whether 17HSD type 1 or type 2 is
      of greatest importance in breast tumour development is still not clear. The aim
      of this study was to investigate how the loss of 17HSD type 2 expression, using
      siRNA in the non-tumour breast epithelial cells HMEC (human mammal epithelial
      cells) and MCF10A, and gain of 17HSD type 2 expression, using transient
      transfection in the breast cancer derived cell lines MCF7 and T47D, affect
      oestradiol conversion and proliferation rate measured as S-phase fraction. We
      further investigated how this was related to the endogenous expression of 17HSD
      type 1 and oestradiol receptors in the examined cell lines. The oestradiol level
      in the medium changed significantly in the MCF7 transfected cells and the siRNA
      treated HMEC cells, but not in T47D or MCF10A. The S-phase fraction decreased in
      the 17HSD type 2-transfected MCF7 cells and the siRNA-treated HMEC cells. The
      results seemed to be dependent on the endogenous expression of 17HSD type 1 and
      the oestradiol receptors. In conclusion, we found that high or low levels of
      17HSD type 2 affected the oestradiol concentration significantly. However, the
      response was dependent on the endogenous expression of 17HSD type 1. Expression
      of 17HSD type 1 seems to be dominant to 17HSD type 2. Therefore, it may be
      important to investigate a ratio between 17HSD type 1 and 17HSD type 2.

PMID- 16954437
TI  - Stat5 expression predicts response to endocrine therapy and improves survival in
      estrogen receptor-positive breast cancer.
AB  - Constitutively activated signal transducers and activators of transcription
      (Stats), in particular Stat3 and Stat5, have been demonstrated to directly
      contribute to oncogenesis by stimulating cell proliferation and preventing
      apoptosis in various cancers. Stat3 is essential in mammary gland epithelial cell
      apoptosis and involution, whereas Stat5 is well established as a key factor in
      mammary epithelial cell growth and differentiation. Crosstalk between Stats and
      estrogen receptor (ER) has been demonstrated by several laboratories and we have
      focused on the role of Stat5 in ER-positive breast cancer. Using
      immunohistochemical techniques, we examined the expression of Stat3 and Stat5 in
      517 human breast cancer tissues and analyzed their significance for prognosis and
      prediction of response to endocrine therapy. Stat5 expression was significantly
      correlated with histological grade (P<0.0001), ER (P=0.02), and progesterone
      receptor (P=0.026) expression. There was no difference between Stat3 expression
      and clinicopathological factors. In 346 patients with ER-positive breast cancer,
      patients with Stat5 positive tumors had significantly increased overall survival
      (P=0.0009) in multivariate analysis. There were 70 patients who received
      endocrine therapy as first-line treatment for metastatic breast cancer at
      relapse. The patients whose primary breast tumors were Stat5 positive, had
      significantly better response to endocrine therapy (P=0.04), and longer survival
      after relapse (P=0.0003), than those whose tumors were Stat5 negative. The
      present study demonstrates for the first time that Stat5 is a predictive factor
      for endocrine therapy response and a strong prognostic molecular marker in ER
      positive breast cancer. Our data suggest that the expression of Stat5 is helpful
      in selecting patients who may benefit from endocrine therapy.

PMID- 16954438
TI  - The role of angiotensin II in the regulation of breast cancer cell adhesion and
      invasion.
AB  - As breast cancer remains the most common cause of cancer death in women, there is
      a continuing need not only to further characterise the processes of cancer
      progression, but also to improve accuracy of prognostic markers. Breast
      epithelial cells express components of the renin angiotensin system and studies
      suggest that these may be altered in disease progression. In addition, altered
      integrin expression correlates with lymph node metastasis. The aim of this study
      was to investigate the relationship between angiotensin II (AII) and integrins in
      breast tissue and, in particular, their role in breast cancer cell metastasis.
      Using in vitro assays, AII (10(-6) M)-treated MCF-7 and T47D breast cancer cells
      both show reduced adhesion to extracellular matrix proteins collagen-,
      fibronectin- and laminin-coated wells (P<0.001) and reduced invasion through
      collagen-, fibronectin- and laminin-coated membranes (P<0.05). This action was
      inhibited by co-treatment with the angiotensin type 1 receptor (AT1R) antagonist
      losartan (10(-5) M). The addition of the AT2R inhibitor PD123319 (10(-5) M) to
      AII-treated cells had no significant effect. Semi-quantitative reverse
      transcriptase-PCR and western blotting revealed that cells treated with AII (10(
      6) M) expressed lower levels of both integrin alpha3 and beta1. Using specific
      inhibitors, this was shown to occur through protein kinase C signalling. These
      data suggest that AII reduces cell adhesion and invasion through the type 1
      receptor and that this effect may be due to reduced expression of integrins, and
      in particular alpha3 and beta1.

PMID- 16954439
TI  - Vascular endothelial growth factor induces proliferation of breast cancer cells
      and inhibits the anti-proliferative activity of anti-hormones.
AB  - Increased levels of vascular endothelial growth factor (VEGF) are associated with
      a poor response of breast cancer to anti-hormone treatment. Although VEGF is
      regarded as an endothelial-specific growth factor, recent reports have shown that
      VEGF can promote proliferation of other cell types, including breast tumor cells.
      We have characterized the proliferative effects of VEGF in breast cancer cell
      lines that are commonly used for understanding the role of estrogens, progestins,
      and anti-hormones on tumor growth. Since steroid hormones can increase the level
      of VEGF in certain breast cancer cells, we evaluated the effects of exogenous
      VEGF on the growth-suppressive effects of anti-estrogen (ICI 182,780) and RU-486
      (anti-progestin mifepristone) in human breast cancer cells. VEGF165 and VEGF121
      increased the proliferation of tumor cell lines that expressed VEGFR-2 (VEGF
      receptor 2) (flk/kdr) via the extracellular signal-regulated kinase/mitogen
      activated protein kinase (ERK/MAPK) pathway. Furthermore, VEGF induced the
      expression of the anti-apoptotic protein Bcl-2 and blocked down-regulation of Bcl
      2 by ICI 182,780 and induced Bcl-2 in BT-474 and T47-D cells even in the presence
      of RU-486. Increased Bcl-2 levels in response to VEGF were associated with
      increased proliferation and survival of tumor cells even in the presence of anti
      hormones. These results suggest that VEGF stimulates proliferation of VEGFR2
      positive tumor cells, promotes survival via the expression and activity of Bcl-2
      and overrides the growth-suppressive effects of anti-hormones. This represents a
      potential explanation for anti-hormone resistance and tumor progression in
      clinical samples. Thus, it may be useful to use combined modality treatment
      involving anti-hormones and anti-angiogenic agents to treat breast cancers that
      express elevated levels of VEGF.

PMID- 16954440
TI  - Role of carbonic anhydrase IX expression in prediction of the efficacy and
      outcome of primary epirubicin/tamoxifen therapy for breast cancer.
AB  - The purpose of this study is to investigate the role of carbonic anhydrase IX
      (CAIX) expression in predicting the response to epirubicin and disease-free
      survival (DFS) in breast cancer patients enrolled in a single institution trial
      of primary anthracycline and tamoxifen therapy. CAIX expression was assessed in
      183 patients with T2-4 N0-1 breast cancer enrolled in a randomized trial
      comparing four cycles of single agent epirubicin versus epirubicin+tamoxifen as
      primary systemic treatment. All patients received postoperatively four cycles of
      the four weekly i.v. cyclophosphamide, methotrexate, 5-fluorouracil regimen.
      Patients with estrogen receptor (ER)-positive primary tumors received 5 years of
      adjuvant tamoxifen. Pretreatment, p53 (P=0.007), c-erbB2 (P<0.01), and Ki67
      (P=0.02) were directly associated with CAIX expression, while bcl2 (P<0.000) and
      ER (P=0.000) and progesterone receptor (PgR; P<0.01) were inversely correlated.
      In multivariate analysis, only high p53 and low bcl2 were independently
      associated with CAIX positivity. CAIX immunostaining was significantly associated
      with poor outcome for DFS (P<0.002) and overall survival (P=0.001). In
      multivariate analysis, a significant interaction was found between CAIX and
      markers of hormone sensitivity, bcl2 (P=0.01), ER (P=0.02), PgR (P=0.02), and
      lymph node involvement (P=0.04), in predicting DFS. Presently, there are few
      clinical markers of resistance to tamoxifen treatment in ER-positive tumors. CAIX
      expression in breast cancer patients shows a negative predictive role of
      treatment efficacy in ER-positive patients on the adjuvant tamoxifen after
      primary chemo-endocrine therapy. Studies investigating the effects of pH on
      tamoxifen uptake and the effects of therapy with CA inhibitors are planned.

PMID- 16954441
TI  - Angiogenesis and lymphangiogenesis in thyroid proliferative lesions: relationship
      to type and tumour behaviour.
AB  - The role of angiogenesis and lymphangiogenesis in thyroid cancer pathogenesis has
      not been elucidated. Patterns for tumour behaviour and metastasic spread vary
      according to tumour type and whether differences in the angiogenic or
      lymphangiogenic phenotype influence the route for tumour metastases or determine
      a more aggressive behaviour has not been fully explored. The angiogenic and
      lymphangiogenic phenotypes of a large cohort of thyroid proliferative lesions
      (n=191) were studied. Using immunohistochemistry for CD34, lymphatic vessel
      endothelial receptor-1 (LYVE-1) (specific markers for vascular and lymphatic
      endothelium respectively), vascular endothelial growth factor (VEGF-A), VEGF-C
      and fibroblast growth factor-2 (FGF-2), this study analyses microvascular density
      (MVD), lymphatic vascular density (LVD), and expression of angiogenic and
      lymphangiogenic factors in normal thyroid (NT; n=19), multinodular goitre (n=25),
      toxic multinodular goitre (n=8), Graves' hyperplasia (n=22), follicular adenoma
      (n=54), papillary carcinoma (PC; n=27), incidental papillary microcarcinoma (PMC;
      n=8), follicular carcinoma (FC; n=20) and medullary carcinoma (MC; n=8). MVD was
      decreased in proliferative lesions, benign and malignant, compared with NT
      (P<0.0001). In contrast, VEGF-A expression was increased in thyroid carcinomas
      (PC, FC and MC) when compared with PMC, benign lesions and NT (P<0.0001). LVD was
      higher in PC and PMC (P=0.001), and VEGF-C expression was increased in PC
      (P<0.0001). Despite higher LVD and increased expression of VEGF-A and VEGF-C in
      thyroid cancers, these markers were not related to poor prognosis in terms of
      tumour size, multifocality and/or presence of lymphatic or distant metastases. In
      conclusion, angiogenesis is reduced in thyroid proliferative lesions compared
      with NT tissue. However, VEGF-A expression is upregulated in thyroid cancers.
      Lymphangiogenesis and VEGF-C expression are increased in thyroid tumours prone to
      lymphatic metastases. This may be an important mechanism underlying the
      differences in metastatic behaviour between papillary and follicular thyroid
      cancer.

PMID- 16954442
TI  - An in-frame complex germline mutation in the juxtamembrane intracellular domain
      causing RET activation in familial medullary thyroid carcinoma.
AB  - Activating mutations of the RET proto-oncogene are associated with inherited
      syndromes, multiple endocrine neoplasia (MEN2A/2B) and with familial and sporadic
      medullary thyroid cancer (MTC). Single base pair missense mutations in the
      extracellular Cys-rich domain are responsible for most MEN2A and familial MTC
      (FMTC) cases. Rarely, somatic deletions and germline duplications have been
      described in sporadic MTC and in FMTC. We report the detection and functional
      studies of a deletion/insertion in exon 11 (c.2646delGinsTTCT) associated with
      FMTC. This in-frame complex rearrangement leads to an Asn to Lys change
      (Lys666Asn) and to a Ser insertion. The mutation was found in the proband, who
      was diagnosed with metastatic MTC at 41 years, and in her son, who presented
      diffuse C-cells hyperplasia at 4 years of age. The mutation displayed a
      transforming activity stronger than Ret wild type (Ret-WT) at the focus formation
      assay and functional analyses after transient and stable transfection revealed an
      increased autophosphorylation, indicating the constitutive activation of the
      receptor. The transforming activity may be favoured by an increased stabilization
      of the fully mature form of the mutant receptor. Dimerization assay demonstrated
      that the activation mechanism of the complex mutation is not mediated by stable
      dimer formation. Computational analysis predicted nonconservative alterations in
      the mutant protein consistent with a possible modification of the conformation of
      the receptor. In conclusion, the first molecular studies on a complex germline
      RET mutation lying in the juxtamembrane region of the receptor are reported.
      Functional analyses showed that alterations at this level too can lead to a
      ligand independent Ret activation.

PMID- 16954443
TI  - Octreotide promotes apoptosis in human somatotroph tumor cells by activating
      somatostatin receptor type 2.
AB  - Somatostatin analogs currently used in the treatment of acromegaly and other
      neuroendocrine tumors inhibit hormone secretion and cell proliferation by binding
      to somatostatin receptor type (SST) 2 and 5. The antiproliferative pathways
      coupled to these receptors have been only partially characterized. The aim of
      this study was to evaluate the effect of octreotide and super selective SST2
      (BIM23120) and SST5 (BIM23206) analogs on apoptotic activity and apoptotic gene
      expression in human somatotroph tumor cells. Eight somatotroph tumors expressing
      similar levels of SST2 and SST5 evaluated by real-time PCR and western blot
      analyses were included in the study. In cultured cells obtained from these
      tumors, octreotide induced a dose-dependent increase of caspase-3 activity (160+/
      20% vs basal at 10 nM) and cleaved cytokeratin 18 levels (172+/-25% vs basal) at
      concentrations higher than 0.1 nM. This effect was due to SST2 activation since
      BIM23120 elicited comparable responses, while BIM23206 was ineffective. BIM23120
      stimulated apoptosis was dependent on phosphatases, since it was abrogated by the
      inhibitor orthovanadate, and independent from the induction of apoptosis-related
      genes, such as p53, p63, p73, Bcl-2, Bax, BID, BIK, TNFSF8, and FADD. In
      somatotroph tumors, both BIM23120 and BIM2306 caused growth arrest as indicated
      by the increase in p27 and decrease in cyclin D1 expression. In conclusion, the
      present study showed that octreotide-induced apoptosis in human somatotroph tumor
      cells by activating SST2. This effect, together with the cytostatic action
      exerted by both SST2 and SST5 analogs, might account for the tumor shrinkage
      observed in acromegalic patients treated with long-acting somatostatin analogs.

PMID- 16954444
TI  - Gastrointestinal stromal tumors express the orexigen ghrelin.
AB  - Expression of the neuroendocrine marker synaptic vesicle protein 2 (SV2) has been
      reported in a few cases of gastrointestinal stromal tumors (GISTs). The goal of
      the present study was to assess the relevance of this finding and identify a
      possible hormone production in these tumors. We chose to study the orexigen
      ghrelin and its receptor, since these patients are seldom cachexic, even in
      advanced disease stages. We investigated ghrelin expression by means of
      immunohistochemistry on frozen or paraffin-embedded sections from 22 GISTs from a
      well-characterized patient material. Expression of the growth hormone
      secretagogue receptor, the ghrelin receptor, was investigated in a subset of
      lesions. In six tumors, mRNA levels of ghrelin, the ghrelin receptor, and SV2
      were analyzed by real-time quantitative PCR. Totally 17 out of 22 tumors showed
      immunoreactivity for ghrelin. Five out of ten tumors were immunoreactive for the
      ghrelin receptor, and all of these co-expressed ghrelin. All tumors expressed
      ghrelin, ghrelin receptor, and SV2 mRNA. GISTs frequently express SV2, ghrelin,
      and its receptor, indicating the presence of autocrine/paracrine loops.

PMID- 16954445
TI  - Cyclic changes and hormonal regulation of annexin IV mRNA and protein in human
      endometrium.
AB  - Annexin IV (ANXA4) belongs to a ubiquitous family of Ca(2+)-dependent
      phospholipid-binding proteins. ANXA4 has been shown to be involved in a range of
      physiological functions including ion channel regulation, exocytosis and Ca(2+)
      dependent signal transduction. The aims of this study were to fully characterize
      ANXA4 mRNA and protein in human endometrium during the menstrual cycle and to
      investigate the hormonal regulation of ANXA4. ANXA4 mRNA expression was
      quantified by real-time PCR in fresh endometrial tissue from cycling women, and
      protein expression was analysed by immunohistochemistry and western blotting.
      Hormonal regulation of ANXA4 transcription and translation was investigated using
      an endometrial explant system. ANXA4 mRNA was significantly up-regulated during
      mid-secretory (MS) and late-secretory (LS) phases compared with proliferative
      phases during the menstrual cycle. ANXA4 protein was localized to glandular and
      luminal epithelium and was present in high levels throughout the menstrual cycle
      except during early-secretory (ES) phase, when it was significantly reduced. Our
      data also show that, in proliferative explants, progesterone significantly
      increased the ANXA4 mRNA and protein after 48h in culture. Estrogen did not have
      any significant effects. This is the first study to show that ANXA4 transcription
      and translation are regulated by progesterone and suggests that ANXA4 may be
      important in regulating ion and water transport across the endometrial
      epithelium.

PMID- 16954446
TI  - Reversible acute adrenal insufficiency caused by fluconazole in a critically ill
      patient.
AB  - A 38 year old man with history of obstructive sleep apnea and polycythaemia
      presented with hypercapnic respiratory failure that required intubation. He
      developed fever with infiltrates on chest radiography that required empiric
      antifungal therapy with fluconazole along with broad spectrum antibiotics. He
      developed acute adrenal insufficiency that recovered after fluconazole was
      stopped. It is believed that this complication of adrenal suppression
      attributable to fluconazole is underrecognised and it may be prudent to monitor
      all critically ill patients who are given fluconazole for this complication.

PMID- 16954447
TI  - AIDS in India.

PMID- 16954448
TI  - Twenty four hour ambulatory blood pressure monitoring: a new tool for determining
      cardiovascular prognosis.
AB  - Twenty four hour ambulatory blood pressure monitoring (24-H ABPM) plays an
      important part in the management of subjects with suspected and confirmed
      disorders of blood pressure regulation. This article reviews the prognostic
      significance of various aspects of the 24-H ABPM and describes the authors
      experience in Chesterfield. Over the course of 12 month period from 1 August
      2002, 1264 subjects had 24-ABPM. A total of 1187 (93.91%) subjects were included
      in this study, with mean age of 59.30 years and male:female ratio was 46%: 54 %.
      Fifty two (4.38%) of the subjects had all of the seven features associated with
      an adverse prognosis. Only 82 (6.90%) subjects had none of the seven adverse
      prognostic features with the remainder having one or more adverse prognostic
      features.

PMID- 16954449
TI  - Management of thyroid disorders.
AB  - Autoimmune thyroid disease is the predominant form of thyroid dysfunction in the
      developed world. Although its precise cause is currently unclear, principles of
      management have been established. There is a vigorous debate about the management
      of the increasingly commonly recognised subclinical forms of thyroid dysfunction
      despite recent recommendations. Nodular thyroid disease and thyroid carcinoma
      have received wide attention. The effects of drugs and pregnancy on thyroid
      function have also been investigated widely. This short review attempts to give
      an overview and clarify the current management of common thyroid disorders.

PMID- 16954450
TI  - Micronutrients in health and disease.
AB  - Micronutrients play a central part in metabolism and in the maintenance of tissue
      function. An adequate intake therefore is necessary, but provision of excess
      supplements to people who do not need them may be harmful. Single micronutrient
      deficiency states are comparatively easily recognised and treated. Subclinical
      deficiency, often of multiple micronutrients, is more difficult to recognise, and
      laboratory assessment is often complicated by the acute phase response. Clinical
      benefit is most likely in those people who are severely depleted and at risk of
      complications, and is unlikely if this is not the case. There is little evidence
      for supplements leading to a reduction in the incidence of infections in the
      elderly population, in coronary artery disease, or in malignant disease. The best
      evidence for benefit is in critical illness, and in children in developing
      countries consuming a deficient diet. More clinical trials are required with good
      clinical outcomes to optimise intake in prevention and treatment of disease.

PMID- 16954451
TI  - Post-stroke seizure and post-stroke epilepsy.
AB  - Post-stroke seizure and post-stroke epilepsy are common causes of hospital
      admissions, either as a presenting feature or as a complication after a stroke.
      They require appropriate management and support in long term. With an
      increasingly ageing population, and age itself being an independent risk factor
      for stroke, the incidence and prevalence of post-stroke seizure and post-stroke
      epilepsy is likely to increase. This article examines aetiology, clinical
      presentation, and presents a management outline of these conditions with
      particular focus on adults. The aim of this review article is to provide the
      clinicians with background information and recommendations.

PMID- 16954452
TI  - Potential role of dendritic cells for progression of atherosclerotic lesions.
AB  - Atherosclerosis is a lipid related chronic inflammatory disease in which immune
      mechanisms play a pivotal part. Its lesion is filled with large numbers of immune
      cells. In 1995 dendritic cells (DCs) were identified in atherosclerotic plaques
      and thought to play an important part in atherogenesis. DCs express MHCI and ll,
      HLA-DR, CD1a, ICAM-1 and VCAM1 on their surfaces, and this explains their unique
      ability to activate naive T cells. The risk factors for atherosclerosis are the
      factors for DCs' activation and migration. Mature DCs are capable of presenting
      antigen to T cells, which play an important part in progression of disease.
      Statin and diltiazem have been shown to protect endothelial function by
      suppressing the function of DCs and play an important part in preventing
      atherosclerosis.

PMID- 16954453
TI  - The Foundation Programme assessment tools: an opportunity to enhance feedback to
      trainees?
AB  - The recent change in working patterns of doctors in training has meant that the
      traditional systems of education are under increasing pressure and that there is
      the need to maximise new opportunities for learning. One new opportunity may
      arise after the introduction of the mandatory assessment systems (Mini-CEX,
      DOPPS, Multi-source feedback, and Case based discussion) in the Foundation
      Programmes. In this review the new assessment procedures for the Foundation
      Programmes are outlined and the potential of these assessments (using Mini-CEX as
      main example) as an opportunity to give feedback to trainees discussed. The
      importance of feedback in professional development and some of the techniques
      available for giving feedback are described. The Foundation Programme assessments
      will occupy a significant amount of trainees' and trainers' time and it is
      important that opportunity for feedback and learning is maximised.

PMID- 16954454
TI  - Papilloedema or pseudopapilloedema? Computed tomography to the rescue!

PMID- 16954455
TI  - Ageing changes in the eye.
AB  - Ageing changes occur in all the structures of the eye causing varied effects.
      This article attempts to review the parameters of what is considered within the
      "normal limits" of ageing so as to be able to distinguish those conditions from
      true disease processes. Improving understanding of the ageing changes will help
      understand some of the problems that the ageing population faces.

PMID- 16954456
TI  - Cyclooxygenase-2 plays an essential part in cardioprotection of delayed phase of
      recombinant human erythropoietin preconditioning in rats.
AB  - AIMS: To study the cardioprotection of recombinant human erythropoietin (rhEPO)
      preconditioning (EPC) and to investigate the role and possible mechanism of
      cyclooxygenase (COX)-2 in the delayed phase of EPC. METHODS: In phase 1,
      myocardial ischaemia reperfusion (I-R) rat model was established by 30 minutes
      ligation of left descending coronary and three hours of reperfusion. Rats were
      given 0.9% saline solution or rhEPO 24 hours before I-R protocol. COX-2 selective
      inhibitor celecoxib was given for further investigation of the cardioprotection
      of EPC. At the end of I-R protocol, infarct sizes were measured and
      ultrastructural organisations were studied. In phase 2, myocardial COX-2 mRNA
      expressions and prostaglandins (PGs) contents were studied in different groups
      after euthanasia. RESULTS: It was found that EPC could elicit potent
      cardioprotection against I-R injury, shown by reduction of infarct size and
      improvement of ultrastructural organisation; whereas administration of celecoxib
      resulted in complete loss of this protection. EPC resulted in robust increase in
      COX-2 mRNA and PGs levels that were also abrogated by celecoxib. CONCLUSIONS: COX
      2 plays an essential part in cardioprotection of the delayed phase of EPC in
      rats, which might be related to actions of PGE(2) or PGI(2), or both.

PMID- 16954457
TI  - Anti-inflammatory action of diltiazem in patients with unstable angina.
AB  - BACKGROUND AND AIMS: Plasma concentrations of anti-inflammatory cytokine
      interleukin 10 (IL10) have been shown to be decreased in patients with unstable
      angina (UA) suggesting that reduced concentrations of IL10 may favour plaque
      instability and the development of acute coronary syndromes. Diltiazem has been
      shown to exert beneficial effects in patients with acute coronary syndrome.
      However, the potential influence of diltiazem on the anti-inflammatory cytokine
      IL10 in patients with UA has not been investigated. This study was designed to
      find out the effects of diltiazem on IL10 in UA patients. METHODS AND RESULTS:
      Thirty patients with UA were divided into two groups: group R and group D (n =
      15). Group R was given routine pharmacotherapy for UA, and group D was given
      routine pharmacotherapy plus diltiazem. Plasma concentrations of IL10 in these
      groups were measured before the start of the treatment and 28 days after
      treatment. Plasma concentrations of IL10 in 15 normal subjects (group N) were
      also measured. Patients with UA had decreased concentrations of IL10 compared
      with normal group. Four weeks after treatment, plasma concentrations of IL10
      significantly increased in group D compared with that before treatment, but the
      increase in IL10 values in group R was not significant. CONCLUSIONS: These
      findings showed that concentrations of anti-inflammatory IL10 are considerably
      decreased in UA patients and diltiazem treatment leads to a significant increase
      in IL10 concentrations.

PMID- 16954458
TI  - Extrinsic allergic alveolitis: comparative study of the bronchoalveolar lavage
      profiles and radiological presentation.
AB  - INTRODUCTION: Extrinsic allergic alveolitis (EAA) is an immunologically mediated
      interstitial lung disease. The abnormalities in the bronchoalveolar lavage (BAL)
      fluid cell counts are almost always seen in patients with EAA according to the
      stage of the disease. The aim of this retrospective study was to find out how the
      BAL lymphocyte count, percentage of lymphocytes expressing HLA-DR, CD4/CD8 T cell
      ratio in BAL fluid, and the concentration of immunoglobulin G in serum correspond
      to the inflammatory activity of the disease. METHODS: The study included 14
      patients with EAA. BAL fluid samples were obtained and processed for cytological
      and cytometric analysis. Immunoglobulin G serum concentrations were measured.
      High resolution computed tomography (HRCT) scoring system modified by Gay was
      used for establishing the alveolar and interstitial score in each patient.
      CONCLUSIONS: It was found that subjects with normal value of CD4/CD8 ratio in BAL
      fluid had higher interstitial HRCT score. Clinical presentation, continuous
      exposure to the causative antigens, and BAL lymphocyte count positively
      correlated with the alveolar HRCT score. It is proposed that the increased BAL
      lymphocyte count could be the predictor of the inflammatory activity of the
      disease, especially in people with lasting exposure to the offending antigen.

PMID- 16954459
TI  - Pulmonary leptospirosis: an excellent response to bolus methylprednisolone.
AB  - BACKGROUND: This case series analyses the beneficial effect of methylprednisolone
      in pulmonary leptospirosis, which usually has an aggressive course and grave
      outcome. METHODS: 30 patients of pulmonary leptospirosis were evaluated. The
      initial 13 patients did not receive corticosteroids while the remaining 17 all
      received bolus methylprednisolone one gram intravenously for three days followed
      by oral prednisolone 1 mg/kg for seven days, on the basis of occasional case
      reports of benefit in pulmonary leptospirosis. APACHE III and lung injury scores
      of similar severity were considered while comparing outcomes in those who
      received methylprednisolone with those who did not. RESULTS: Dyspnoea and
      haemoptysis were the commonest symptoms in those with pulmonary manifestations.
      Overall mortality was 18% (3 of 17) in patients who received methylprednisolone,
      as compared with 62% (8 of 13 patients) in those who did not (p<0.02). In
      patients with established acute lung injury (ALI score >2.5), five of eight
      patients survived in the subgroup with corticosteroids (37% mortality) while only
      one of nine patients survived in the group that did not receive corticosteroids
      (89% mortality). Corticosteroids affected outcome only if given within the first
      12 hours after the onset of pulmonary manifestations. Mortality seemed to
      correlate with the APACHE scores, and number of quadrants affected on chest
      radiographs, more than with blood gas pressures. CONCLUSIONS: Corticosteroids
      reduce mortality and change outcome significantly when used early in the
      management of pulmonary leptospirosis.

PMID- 16954460
TI  - Perceptions of medical school graduates and students regarding their academic
      preparation to teach.
AB  - PURPOSE: How medical students learn and develop the characteristics associated
      with good teaching in medicine is not well known. Information about this process
      can improve the academic preparation of medical students for teaching
      responsibilities. The purpose of this study was to determine how different
      experiences contributed to the knowledge, skills, and attitudes of medical school
      graduates and students regarding medical teaching. METHODS: A questionnaire was
      developed, addressing reliability and validity considerations, and given to first
      year residents and third year medical students (taught by those residents).
      Completed questionnaires were collected from 76 residents and 110 students (81%
      of the sample group). Item responses were analysed using descriptive and
      inferential statistics. RESULTS: Most residents (n = 54; 71%) positively viewed
      opportunities they had to practice teaching when they were seniors. Residents
      rated three activities for learning to teach highest: (1) observing teachers as
      they teach; (2) reviewing the material to be taught; and (3) directly teaching
      students; representing both individual and participatory ways of learning.
      Residents' self ratings of teaching behaviours improved over time and this self
      assessment by the residents was validated by the students' responses. Comparison
      between residents' self ratings and students' views of typical resident teaching
      behaviours showed agreement on levels of competence, confidence, and motivation.
      The students rated characteristics of enthusiasm, organisation, and fulfilment
      lower (p<0.002) than residents rated themselves. CONCLUSIONS: The residents and
      students in this study viewed academic preparation for teaching responsibilities
      positively and showed agreement on characteristics of good teaching that may be
      helpful indicators in the process of developing medical teachers.

PMID- 16954461
TI  - Comparison of transthoracic echocardiography with harmonic imaging with
      transoesophageal echocardiography for the diagnosis of patent foramen ovale.
AB  - The optimal diagnostic method for patent foramen ovale is currently unclear. This
      study compared bubble contrast second harmonic transthoracic (TTE) and
      transoesophageal echocardiography (TOE) on 87 consecutive patients referred for
      TOE for all indications. A right left shunt was diagnosed in 34 cases (39%), with
      TTE positive in 26 cases (sensitivity 76.5%), TOE positive in 27 cases
      (sensitivity 79.4%). Pitfalls of TTE included quality of echo and left sided
      valve lesions, and for TOE the ability to perform an adequate Valsalva manoeuvre.
      In conclusion, both tests have similar sensitivity and should be viewed as
      complementary modalities.

PMID- 16954462
TI  - Secular trends in the medical discharge summary in an acute medical hospital.
AB  - BACKGROUND: Although recent research has reported an evolution in the level of
      medical care, little is known about secular trends in the medical discharge
      summary. METHODS: The audit evaluated the evolution of discharge summary abstract
      over a decade in an acute medicine hospital among three successive periods of
      1994, 2000, and 2005. RESULTS: Of the 140 random samples of discharge summaries,
      significant between-cohort difference existed in the logarithm transformed length
      of discharge summary; the median length of discharge summary increased from 11
      lines in 1994 to 26 lines in 2005 (p<0.001 corrected for multiple comparison).
      The closest univariate associations of discharge summary length were positively
      with the year of hospitalisation, length of stay, length of wordings about
      discharge plan and duplication of previous discharge summary, and negatively with
      clinical or planned admission (all p<0.01). In a multiple linear regression
      analysis, the year of patient admission correlated significantly with the length
      of discharge summary (p<0.001). CONCLUSIONS: Over the 10 year study period,
      significant secular trends were seen in the discharge summary length and
      discharge plan documentation. The causes and implications for these trends
      deserve further investigation.

PMID- 16954463
TI  - Development and evaluation of therapeutically relevant predictive classifiers
      using gene expression profiling.

PMID- 16954464
TI  - Assessing breast cancer risk: evolution of the Gail Model.

PMID- 16954465
TI  - Tissue banks trigger worry about ownership issues.

PMID- 16954466
TI  - Realistic rodents? Debate grows over new mouse models of cancer.

PMID- 16954467
TI  - NCI launches an innovative design for a breast cancer clinical trial.

PMID- 16954468
TI  - New technologies aim to find cancer in the blood.

PMID- 16954469
TI  - Three new drugs available to fight kidney cancer.

PMID- 16954470
TI  - Stat bite: Kidney cancer incidence, 2000-2003.

PMID- 16954471
TI  - Validation and clinical utility of a 70-gene prognostic signature for women with
      node-negative breast cancer.
AB  - BACKGROUND: A 70-gene signature was previously shown to have prognostic value in
      patients with node-negative breast cancer. Our goal was to validate the signature
      in an independent group of patients. METHODS: Patients (n = 307, with 137 events
      after a median follow-up of 13.6 years) from five European centers were divided
      into high- and low-risk groups based on the gene signature classification and on
      clinical risk classifications. Patients were assigned to the gene signature low
      risk group if their 5-year distant metastasis-free survival probability as
      estimated by the gene signature was greater than 90%. Patients were assigned to
      the clinicopathologic low-risk group if their 10-year survival probability, as
      estimated by Adjuvant! software, was greater than 88% (for estrogen receptor [ER]
      positive patients) or 92% (for ER-negative patients). Hazard ratios (HRs) were
      estimated to compare time to distant metastases, disease-free survival, and
      overall survival in high- versus low-risk groups. RESULTS: The 70-gene signature
      outperformed the clinicopathologic risk assessment in predicting all endpoints.
      For time to distant metastases, the gene signature yielded HR = 2.32 (95%
      confidence interval [CI] = 1.35 to 4.00) without adjustment for clinical risk and
      hazard ratios ranging from 2.13 to 2.15 after adjustment for various estimates of
      clinical risk; clinicopathologic risk using Adjuvant! software yielded an
      unadjusted HR = 1.68 (95% CI = 0.92 to 3.07). For overall survival, the gene
      signature yielded an unadjusted HR = 2.79 (95% CI = 1.60 to 4.87) and adjusted
      hazard ratios ranging from 2.63 to 2.89; clinicopathologic risk yielded an
      unadjusted HR = 1.67 (95% CI = 0.93 to 2.98). For patients in the gene signature
      high-risk group, 10-year overall survival was 0.69 for patients in both the low-
      and high-clinical risk groups; for patients in the gene signature low-risk group,
      the 10-year survival rates were 0.88 and 0.89, respectively. CONCLUSIONS: The 70
      gene signature adds independent prognostic information to clinicopathologic risk
      assessment for patients with early breast cancer.

PMID- 16954472
TI  - Prognostic significance of gene expression profiles of metastatic neuroblastomas
      lacking MYCN gene amplification.
AB  - BACKGROUND: The aggressiveness of metastatic neuroblastomas that lack MYCN gene
      amplification varies with age--they are least aggressive when diagnosed in
      patients younger than 12 months and most aggressive when diagnosed in patients
      older than 24 months. However, age at diagnosis is not always associated with
      patient survival. We examined whether molecular classification of metastatic
      neuroblastomas without MYCN gene amplification at diagnosis using gene expression
      profiling could improve the prediction of risk of disease progression. METHODS:
      We used Affymetrix microarrays to determine the gene expression profiles of 102
      untreated primary neuroblastomas without MYCN gene amplification obtained from
      children whose ages at diagnosis ranged from 0.1 to 151 months. A supervised
      method using diagonal linear discriminant analysis was devised to build a
      multigene model for predicting risk of disease progression. The accuracy of the
      model was evaluated using nested cross-validations, permutation analyses, and
      gene expression data from 15 additional tumors obtained at disease progression.
      RESULTS: An expression profile model using 55 genes defined a tumor signature
      that distinguished two groups of patients from among those older than 12 months
      at diagnosis and clinically classified as having high-risk disease, those with a
      progression-free survival (PFS) rate of 16% (95% confidence interval [CI] = 8% to
      28%), and those with a PFS rate of 79% (95% CI = 57% to 91%) (P<.01). These tumor
      signatures also identified two groups of patients with PFS of 15% (95% CI = 7% to
      27%) and 69% (95% CI = 40% to 86%) (P<.01) from among patients who were older
      than 18 months at diagnosis. The gene expression signature of untreated molecular
      high-risk tumors was also present in progressively growing tumors. CONCLUSION:
      Gene expression signatures of tumors obtained at diagnosis from patients with
      clinically indistinguishable high-risk, metastatic neuroblastomas identify
      subgroups with different outcomes. Accurate identification of these subgroups
      with gene expression profiles may facilitate development, implementation, and
      analysis of clinical trials aimed at improving outcome.

PMID- 16954474
TI  - Projecting absolute invasive breast cancer risk in white women with a model that
      includes mammographic density.
AB  - BACKGROUND: To improve the discriminatory power of the Gail model for predicting
      absolute risk of invasive breast cancer, we previously developed a relative risk
      model that incorporated mammographic density (DENSITY) from data on white women
      in the Breast Cancer Detection Demonstration Project (BCDDP). That model also
      included the variables age at birth of first live child (AGEFLB), number of
      affected mother or sisters (NUMREL), number of previous benign breast biopsy
      examinations (NBIOPS), and weight (WEIGHT). In this study, we developed the
      corresponding model for absolute risk. METHODS: We combined the relative risk
      model with data on the distribution of the variables AGEFLB, NUMREL, NBIOPS, and
      WEIGHT from the 2000 National Health Interview Survey, with data on the
      conditional distribution of DENSITY given other risk factors in BCDDP, with
      breast cancer incidence rates from the Surveillance, Epidemiology, and End
      Results program of the National Cancer Institute, and with national mortality
      rates. Confidence intervals (CIs) accounted for variability of estimates of
      relative risks and of risk factor distributions. We compared the absolute 5-year
      risk projections from the new model with those from the Gail model on 1744 white
      women. RESULTS: Attributable risks of breast cancer associated with DENSITY,
      AGEFLB, NUMREL, NBIOPS, and WEIGHT were 0.779 (95% CI = 0.733 to 0.819) and 0.747
      (95% CI = 0.702 to 0.788) for women younger than 50 years and 50 years or older,
      respectively. The model predicted higher risks than the Gail model for women with
      a high percentage of dense breast area. However, the average risk projections
      from the new model in various age groups were similar to those from the Gail
      model, suggesting that the new model is well calibrated. CONCLUSIONS: This new
      model for absolute invasive breast cancer risk in white women promises modest
      improvements in discriminatory power compared with the Gail model but needs to be
      validated with independent data.

PMID- 16954473
TI  - Prospective breast cancer risk prediction model for women undergoing screening
      mammography.
AB  - BACKGROUND: Risk prediction models for breast cancer can be improved by the
      addition of recently identified risk factors, including breast density and use of
      hormone therapy. We used prospective risk information to predict a diagnosis of
      breast cancer in a cohort of 1 million women undergoing screening mammography.
      METHODS: There were 2,392,998 eligible screening mammograms from women without
      previously diagnosed breast cancer who had had a prior mammogram in the preceding
      5 years. Within 1 year of the screening mammogram, 11,638 women were diagnosed
      with breast cancer. Separate logistic regression risk models were constructed for
      premenopausal and postmenopausal examinations by use of a stringent (P<.0001)
      criterion for the inclusion of risk factors. Risk models were constructed with
      75% of the data and validated with the remaining 25%. Concordance of the
      predicted with the observed outcomes was assessed by a concordance (c) statistic
      after logistic regression model fit. All statistical tests were two-sided.
      RESULTS: Statistically significant risk factors for breast cancer diagnosis among
      premenopausal women included age, breast density, family history of breast
      cancer, and a prior breast procedure. For postmenopausal women, the statistically
      significant factors included age, breast density, race, ethnicity, family history
      of breast cancer, a prior breast procedure, body mass index, natural menopause,
      hormone therapy, and a prior false-positive mammogram. The model may identify
      high-risk women better than the Gail model, although predictive accuracy was only
      moderate. The c statistics were 0.631 (95% confidence interval [CI] = 0.618 to
      0.644) for premenopausal women and 0.624 (95% CI = 0.619 to 0.630) for
      postmenopausal women. CONCLUSION: Breast density is a strong additional risk
      factor for breast cancer, although it is unknown whether reduction in breast
      density would reduce risk. Our risk model may be able to identify women at high
      risk for breast cancer for preventive interventions or more intensive
      surveillance.

PMID- 16954475
TI  - Randomized trial of an intervention to improve mammography utilization among a
      triracial rural population of women.
AB  - INTRODUCTION: Mammography is underused by certain groups of women, in particular
      poor and minority women. We developed a lay health advisor (LHA) intervention
      based on behavioral theories and tested whether it improved mammography
      attendance in Robeson County, NC, a rural, low-income, triracial (white, Native
      American, African American) population. METHODS: A total of 851 women who had not
      had a mammogram within the past year were randomly assigned to the LHA
      intervention (n = 433) or to a comparison arm (n = 418) during 1998-2002. Rates
      of mammography use after 12-14 months (as verified by medical record review) were
      compared using a chi-square test. Baseline and follow-up (at 12-14 months)
      surveys were used to obtain information on demographics, risk factors, and
      barriers, beliefs, and knowledge about mammography. Linear regression, Mantel
      Haenszel statistics, and logistic regression were used to compare barriers,
      beliefs, and knowledge from baseline to follow-up and to identify baseline
      factors associated with mammography. RESULTS: At follow-up, 42.5% of the women in
      the LHA group and 27.3% of those in the comparison group had had a mammogram in
      the previous 12 months (relative risk = 1.56, 95% confidence interval [CI] = 1.29
      to 1.87). Compared with those in the comparison group, women in the LHA group
      displayed statistically significantly better belief scores (difference = 0.46
      points on a 0-10 scale, 95% CI = 0.15 to 0.77) and reduced barriers at follow-up
      (difference = -0.77 points, 95% CI = -1.02 to -0.53), after adjusting for
      baseline scores. CONCLUSIONS: LHA interventions can improve mammography
      utilization. Future studies are needed to assess strategies to disseminate
      effective LHA interventions to underserved populations.

PMID- 16954476
TI  - Cyclin D1 overexpression and response to bortezomib treatment in a breast cancer
      model.
AB  - BACKGROUND: Cyclin D1 is frequently overexpressed in breast cancer, and its
      overexpression is, surprisingly, associated with improved survival. One potential
      mechanism for this association involves signal transducer and activator of
      transcription 3 (STAT3). METHODS: Cyclin D1 and STAT3 expression were assessed in
      human tumors using microarray analysis and in breast cancer cell lines HBL100,
      T47D, MCF7, MDA-MB-453, and BT20 and in HBL100 and T47D cells stably
      overexpressing cyclin D1 using immunoblot analysis. Cyclin D1 protein was
      stabilized by treatment with the proteasome inhibitor bortezomib, and the effects
      on STAT3 expression in vitro was determined by using immunoblotting and on
      xenograft tumor growth and apoptosis in vivo was determined by using terminal
      deoxyuridine nick-end labeling assays. All statistical tests were two-sided.
      RESULTS: Tumors with high cyclin D1 expression (n = 17) had low STAT3 expression
      (mean = 274 arbitrary units), and those with low cyclin D1 expression (n = 31)
      had high STAT3 expression (mean = 882 arbitrary units) (P<.001). In HBL100 and
      T47D parental and cyclin D1-overexpressing cells, cyclin D1 overexpression was
      also inversely associated with STAT3 expression, and cyclin D1 directly reduced
      the expression of STAT3. Stabilization of cyclin D1 protein by bortezomib
      treatment further amplified the cyclin D1-dependent repression of STAT3 in vitro
      and slowed tumor growth in vivo (week 7: untreated mean = 185.7 mm3 versus
      treated mean = 136.2 mm3, difference = 49.5 mm3, 95% confidence interval [CI] =
      18 to 81 mm3, P = .007; week 8: untreated mean = 240.2 mm3 versus treated mean =
      157.3 mm3, difference = 82.9 mm3, 95% CI = 9.1 to 156.7 mm3, P = .0014; and week
      9: untreated mean = 256.4 mm3 versus treated mean = 170.2 mm3, difference = 86.2
      mm3, 95% CI = 22.8 to 149.6 mm3, P = .006) and increased apoptosis (untreated
      mean = 19% versus treated mean = 54%, difference = 35%, 95% CI = 24.7% to 45.4%;
      P = .013) of xenograft tumors. CONCLUSIONS: Cyclin D1 repression of STAT3
      expression may explain the association between cyclin D1 overexpression and
      improved outcome in breast cancer. In addition, bortezomib can amplify the
      proapoptotic function of cyclin D1, raising the possibility that cyclin D1 levels
      may be a marker for predicting the response to this novel drug.

PMID- 16954477
TI  - Irradiation-induced pneumonitis mediated by the CD95/CD95-ligand system.
AB  - Pneumonitis is a dose-limiting side effect of radiotherapy. However, the
      underlying mechanisms of irradiation-induced pneumonitis are unclear. Several
      observations suggest that the CD95/CD95-ligand (CD95L) system is involved in this
      process. Therefore, we examined the development of pneumonitis in CD95- and CD95L
      deficient and wild-type mice after single irradiation with 0 or 12.5 Gy by
      measuring breathing frequency, pulmonary resistance, and histopathologic changes.
      Although wild-type mice developed pathognomonic alterations characteristic of
      pneumonitis (judged by alveolar wall thickness, interstitial edema, and
      interstitial and peribronchial inflammation) that paralleled increased breathing
      frequency ratio on days 5-70 (P < .03) with a maximum at day 37 (12.5 Gy, mean
      ratio = 1.05, 95% confidence interval [CI] = 1.01 to 1.08; P = .004 versus 0 Gy,
      mean ratio = 0.997, 95% CI = 0.976 to 1.02; P = .05) and pulmonary resistance
      (day 42, 12.5 Gy, mean = 0.51, 95% CI = 0.44 to 0.58 versus 0 Gy, mean = 0.40,
      95% CI = 0.32 to 0.47; P = .03) after irradiation, no such changes were detected
      in CD95- or CD95L-deficient mice. This report demonstrates for the first time, to
      our knowledge, that the CD95/CD95L system is important for the development of
      irradiation-induced pneumonitis.

PMID- 16954478
TI  - Re: Association between endothelin receptor B nonsynonymous variants and melanoma
      risk.

PMID- 16954479
TI  - The cover. Jar With Both a Plumed Serpent and a Macaw-Headed Serpent.

PMID- 16954480
TI  - A piece of my mind. Swan's way.

PMID- 16954481
TI  - Association of extended work shifts, vascular function, and inflammatory markers
      in internal medicine residents: a randomized crossover trial.

PMID- 16954482
TI  - Resident physicians' use of professional and nonprofessional interpreters: a
      national survey.

PMID- 16954483
TI  - Group writing of letters to the editor as the goal of journal club.

PMID- 16954484
TI  - Extended work duration and the risk of self-reported percutaneous injuries in
      interns.
AB  - CONTEXT: In their first year of postgraduate training, interns commonly work
      shifts that are longer than 24 hours. Extended-duration work shifts are
      associated with increased risks of automobile crash, particularly during a
      commute from work. Interns may be at risk for other occupation-related injuries.
      OBJECTIVE: To assess the relationship between extended work duration and rates of
      percutaneous injuries in a diverse population of interns in the United States.
      DESIGN, SETTING, AND PARTICIPANTS: National prospective cohort study of 2737 of
      the estimated 18,447 interns in US postgraduate residency programs from July 2002
      through May 2003. Each month, comprehensive Web-based surveys that asked about
      work schedules and the occurrence of percutaneous injuries in the previous month
      were sent to all participants. Case-crossover within-subjects analyses were
      performed. MAIN OUTCOME MEASURES: Comparisons of rates of percutaneous injuries
      during day work (6:30 am to 5:30 pm) after working overnight (extended work) vs
      day work that was not preceded by working overnight (nonextended work). We also
      compared injuries during the nighttime (11:30 pm to 7:30 am) vs the daytime (7:30
      am to 3:30 pm). RESULTS: From a total of 17,003 monthly surveys, 498 percutaneous
      injuries were reported (0.029/intern-month). In 448 injuries, at least 1
      contributing factor was reported. Lapse in concentration and fatigue were the 2
      most commonly reported contributing factors (64% and 31% of injuries,
      respectively). Percutaneous injuries were more frequent during extended work
      compared with nonextended work (1.31/1000 opportunities vs 0.76/1000
      opportunities, respectively; odds ratio [OR], 1.61; 95% confidence interval [CI],
      1.46-1.78). Extended work injuries occurred after a mean of 29.1 consecutive work
      hours; nonextended work injuries occurred after a mean of 6.1 consecutive work
      hours. Injuries were more frequent during the nighttime than during the daytime
      (1.48/1000 opportunities vs 0.70/1000 opportunities, respectively; OR, 2.04; 95%
      CI, 1.98-2.11). CONCLUSION: Extended work duration and night work were associated
      with an increased risk of percutaneous injuries in this study population of
      physicians during their first year of clinical training.

PMID- 16954485
TI  - Interns' compliance with accreditation council for graduate medical education
      work-hour limits.
AB  - CONTEXT: Sleep deprivation is associated with increased risk of serious medical
      errors and motor vehicle crashes among interns. The Accreditation Council for
      Graduate Medical Education (ACGME) introduced duty-hour standards in 2003 to
      reduce work hours. OBJECTIVE: To estimate compliance with the ACGME duty-hour
      standards among interns. DESIGN, SETTING, AND PARTICIPANTS: National prospective
      cohort study with monthly Web-based survey assessment of intern work and sleep
      hours using a validated instrument, conducted preimplementation (July 2002
      through May 2003) and postimplementation (July 2003 through May 2004) of ACGME
      standards. Participants were 4015 of the approximately 37 253 interns in US
      residency programs in all specialties during this time; they completed 29 477
      reports of their work and sleep hours. MAIN OUTCOME MEASURE: Overall and monthly
      rates of compliance with the ACGME standards. RESULTS: Postimplementation, 1068
      (83.6%; 95% confidence interval [CI], 81.4%-85.5%) of 1278 of interns reported
      work hours in violation of the standards during 1 or more months. Working shifts
      greater than 30 consecutive hours was reported by 67.4% (95% CI, 64.8%-70.0%).
      Averaged over 4 weeks, 43.0% (95% CI, 40.3%-45.7%) reported working more than 80
      hours weekly, and 43.7% (95% CI, 41.0%-46.5%) reported not having 1 day in 7 off
      work duties. Violations were reported during 3765 (44.0%; 95% CI, 43.0%-45.1%) of
      the 8553 intern-months assessed postimplementation (including vacation and
      ambulatory rotations), and during 2660 (61.5%; 95% CI, 60.0%-62.9%) of 4327
      intern-months during which interns worked exclusively in inpatient settings.
      Postimplementation, 29.0% (95% CI, 28.7%-29.7%) of reported work weeks were more
      than 80 hours per week, 12.1% (95% CI, 11.8%-12.6%) were 90 or more hours per
      week, and 3.9% (95% CI, 3.7%-4.2%) were 100 or more hours per week. Comparing
      preimplementation to postimplementation responses, reported mean work duration
      decreased 5.8% from 70.7 (95% CI, 70.5-70.9) hours to 66.6 (95% CI, 66.3-66.9)
      hours per week (P<.001), and reported mean sleep duration increased 6.1% (22
      minutes) from 5.91 (95% CI, 5.88-5.94) hours to 6.27 (95% CI, 6.23-6.31) hours
      per night (P<.001). However, reported mean sleep during extended shifts decreased
      4.5%, from 2.69 (95% CI, 2.66-2.73) hours to 2.57 (95% CI, 2.52-2.62) hours
      (P<.001). CONCLUSION: In the first year following implementation of the ACGME
      duty-hour standards, interns commonly reported noncompliance with these
      requirements.

PMID- 16954486
TI  - Association of perceived medical errors with resident distress and empathy: a
      prospective longitudinal study.
AB  - CONTEXT: Medical errors are associated with feelings of distress in physicians,
      but little is known about the magnitude and direction of these associations.
      OBJECTIVE: To assess the frequency of self-perceived medical errors among
      resident physicians and to determine the association of self-perceived medical
      errors with resident quality of life, burnout, depression, and empathy using
      validated metrics. DESIGN, SETTING, AND PARTICIPANTS: Prospective longitudinal
      cohort study of categorical and preliminary internal medicine residents at Mayo
      Clinic Rochester. Data were provided by 184 (84%) of 219 eligible residents.
      Participants began training in the 2003-2004, 2004-2005, and 2005-2006 academic
      years and completed surveys quarterly through May 2006. Surveys included self
      assessment of medical errors and linear analog scale assessment of quality of
      life every 3 months, and the Maslach Burnout Inventory (depersonalization,
      emotional exhaustion, and personal accomplishment), Interpersonal Reactivity
      Index, and a validated depression screening tool every 6 months. MAIN OUTCOME
      MEASURES: Frequency of self-perceived medical errors was recorded. Associations
      of an error with quality of life, burnout, empathy, and symptoms of depression
      were determined using generalized estimating equations for repeated measures.
      RESULTS: Thirty-four percent of participants reported making at least 1 major
      medical error during the study period. Making a medical error in the previous 3
      months was reported by a mean of 14.7% of participants at each quarter. Self
      perceived medical errors were associated with a subsequent decrease in quality of
      life (P = .02) and worsened measures in all domains of burnout (P = .002 for
      each). Self-perceived errors were associated with an odds ratio of screening
      positive for depression at the subsequent time point of 3.29 (95% confidence
      interval, 1.90-5.64). In addition, increased burnout in all domains and reduced
      empathy were associated with increased odds of self-perceived error in the
      following 3 months (P=.001, P<.001, and P=.02 for depersonalization, emotional
      exhaustion, and lower personal accomplishment, respectively; P=.02 and P=.01 for
      emotive and cognitive empathy, respectively). CONCLUSIONS: Self-perceived medical
      errors are common among internal medicine residents and are associated with
      substantial subsequent personal distress. Personal distress and decreased empathy
      are also associated with increased odds of future self-perceived errors,
      suggesting that perceived errors and distress may be related in a reciprocal
      cycle.

PMID- 16954487
TI  - Effectiveness of University of California postbaccalaureate premedical programs
      in increasing medical school matriculation for minority and disadvantaged
      students.
AB  - CONTEXT: Many medical schools administer postbaccalaureate premedical programs
      targeting underrepresented minority and disadvantaged students, with the goal of
      increasing the number of these students matriculating into medical school.
      OBJECTIVE: To determine whether University of California (UC) postbaccalaureate
      programs are effective in increasing medical school matriculation rates for
      program participants. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort
      study assessing 5 UC medical school postbaccalaureate programs. The cohort
      comprised 265 participants in the postbaccalaureate programs in the 1999 through
      2002 academic years and a control group of 396 college graduates who applied to
      the programs but did not participate. Of the participants, 66% were
      underrepresented minorities, and for 50% neither parent had attended college.
      MAIN OUTCOME MEASURE: Matriculation by 2005 into a US medical school accredited
      by the Liaison Committee on Medical Education. RESULTS: By 2005, 67.6% of
      participants and 22.5% of controls had matriculated into medical school (P<.001).
      After adjusting for baseline student characteristics, students who participated
      in postbaccalaureate programs had a higher probability of matriculating into
      medical school in a regression model controlling for grade point average and
      demographic characteristics (odds ratio, 6.30; 95% confidence interval, 4.08
      9.72) and in a model further controlling for preparticipation Medical College
      Admissions Test score (odds ratio, 8.06; 95% confidence interval, 4.65-13.97).
      CONCLUSION: Postbaccalaureate premedical programs appear to be an effective
      intervention to increase the number of medical school matriculants from
      disadvantaged and underrepresented groups.

PMID- 16954488
TI  - An educational intervention to improve physician reporting of adverse drug
      reactions: a cluster-randomized controlled trial.
AB  - CONTEXT: Data on the adverse effects of newly marketed drugs are limited.
      Voluntary reporting is an important part of postmarketing surveillance but is
      underused by physicians. OBJECTIVE: To evaluate the effectiveness of educational
      outreach visits for improving adverse drug reaction (ADR) reporting by
      physicians. DESIGN, SETTING, AND PARTICIPANTS: A cluster-randomized controlled
      trial covering all National Health System physicians in the north of Portugal,
      with intervention in March 2004 through July 2004, and 13 to 16 months of follow
      up. A total of 1388 physicians were assigned in 4 spatial clusters to the
      intervention group, and 5063 were assigned in 11 clusters to the control group.
      INTERVENTION: One-hour educational outreach visits tailored to training needs
      identified in a previous study. MAIN OUTCOME MEASURES: Change in total number of
      reported ADRs and number of serious, high-causality, unexpected, and new-drug
      related ADRs, using generalized linear mixed models adjusted for baseline ADR
      reporting, age, specialty, and work setting. RESULTS: At baseline, ADR reporting
      rates (per 1000 physician-years) did not differ significantly between the
      intervention groups and the control groups in reporting ADRs overall (7.6 vs
      11.3), nor did they differ significantly by category: serious, 4.3 vs 6.0; high
      causality, 5.4 vs 7.6; unexpected, 1.6 vs 3.5; and new-drug-related ADRs, 3.7 vs
      3.8. (P>.05 for all comparisons). The control group had no significant increase
      in ADR reports during follow-up. The adjusted increase in ADR reporting rates
      attributable to intervention was 90.19 for total ADRs (95% confidence interval
      [CI], 54.51-125.87; relative risk [RR], 10.23; 95% CI, 3.81-27.51), 30.16 for
      serious ADRs (95% CI, 18.84-41.47; RR, 6.32; 95% CI, 2.09-19.16), 64.90 for high
      causality ADRs (95% CI, 38.38-91.42; RR, 8.75; 95% CI, 3.05-25.07), 28.04 for
      unexpected ADRs (95% CI, 16.25-39.83; RR, 30.21; 95% CI, 4.54-200.84), and 42.17
      for new-drug-related ADRs (95% CI, 21.58-62.76; RR, 8.05; 95% CI, 2.10 -30.83).
      The greatest difference occurred during the first 4 months after intervention,
      but differences remained statistically significant for 12 months. CONCLUSION: A
      targeted outreach program may improve high-quality reporting of ADRs among
      physicians.

PMID- 16954489
TI  - Accuracy of physician self-assessment compared with observed measures of
      competence: a systematic review.
AB  - CONTEXT: Core physician activities of lifelong learning, continuing medical
      education credit, relicensure, specialty recertification, and clinical competence
      are linked to the abilities of physicians to assess their own learning needs and
      choose educational activities that meet these needs. OBJECTIVE: To determine how
      accurately physicians self-assess compared with external observations of their
      competence. DATA SOURCES: The electronic databases MEDLINE (1966-July 2006),
      EMBASE (1980-July 2006), CINAHL (1982-July 2006), PsycINFO (1967-July 2006), the
      Research and Development Resource Base in CME (1978-July 2006), and proprietary
      search engines were searched using terms related to self-directed learning, self
      assessment, and self-reflection. STUDY SELECTION: Studies were included if they
      compared physicians' self-rated assessments with external observations, used
      quantifiable and replicable measures, included a study population of at least 50%
      practicing physicians, residents, or similar health professionals, and were
      conducted in the United Kingdom, Canada, United States, Australia, or New
      Zealand. Studies were excluded if they were comparisons of self-reports, studies
      of medical students, assessed physician beliefs about patient status, described
      the development of self-assessment measures, or were self-assessment programs of
      specialty societies. Studies conducted in the context of an educational or
      quality improvement intervention were included only if comparative data were
      obtained before the intervention. DATA EXTRACTION: Study population, content area
      and self-assessment domain of the study, methods used to measure the self
      assessment of study participants and those used to measure their competence or
      performance, existence and use of statistical tests, study outcomes, and
      explanatory comparative data were extracted. DATA SYNTHESIS: The search yielded
      725 articles, of which 17 met all inclusion criteria. The studies included a wide
      range of domains, comparisons, measures, and methodological rigor. Of the 20
      comparisons between self- and external assessment, 13 demonstrated little, no, or
      an inverse relationship and 7 demonstrated positive associations. A number of
      studies found the worst accuracy in self-assessment among physicians who were the
      least skilled and those who were the most confident. These results are consistent
      with those found in other professions. CONCLUSIONS: While suboptimal in quality,
      the preponderance of evidence suggests that physicians have a limited ability to
      accurately self-assess. The processes currently used to undertake professional
      development and evaluate competence may need to focus more on external
      assessment.

PMID- 16954490
TI  - Mentoring in academic medicine: a systematic review.
AB  - CONTEXT: Mentoring, as a partnership in personal and professional growth and
      development, is central to academic medicine, but it is challenged by increased
      clinical, administrative, research, and other educational demands on medical
      faculty. Therefore, evidence for the value of mentoring needs to be evaluated.
      OBJECTIVE: To systematically review the evidence about the prevalence of
      mentorship and its relationship to career development. DATA SOURCES: MEDLINE,
      Current Contents, Cochrane Database of Systematic Reviews, Database of Abstracts
      of Reviews of Effects, Cochrane Central Register of Controlled Trials, PsycINFO,
      and Scopus databases from the earliest available date to May 2006. STUDY
      SELECTION AND DATA EXTRACTION: We identified all studies evaluating the effect of
      mentoring on career choices and academic advancement among medical students and
      physicians. Minimum inclusion criteria were a description of the study population
      and availability of extractable data. No restrictions were placed on study
      methods or language. DATA SYNTHESIS: The literature search identified 3640
      citations. Review of abstracts led to retrieval of 142 full-text articles for
      assessment; 42 articles describing 39 studies were selected for review. Of these,
      34 (87%) were cross-sectional self-report surveys with small sample size and
      response rates ranging from 5% to 99%. One case-control study nested in a survey
      used a comparison group that had not received mentoring, and 1 cohort study had a
      small sample size and a large loss to follow-up. Less than 50% of medical
      students and in some fields less than 20% of faculty members had a mentor. Women
      perceived that they had more difficulty finding mentors than their colleagues who
      are men. Mentorship was reported to have an important influence on personal
      development, career guidance, career choice, and research productivity, including
      publication and grant success. CONCLUSIONS: Mentoring is perceived as an
      important part of academic medicine, but the evidence to support this perception
      is not strong. Practical recommendations on mentoring in medicine that are
      evidence-based will require studies using more rigorous methods, addressing
      contextual issues, and using cross-disciplinary approaches.

PMID- 16954491
TI  - Instruments for evaluating education in evidence-based practice: a systematic
      review.
AB  - CONTEXT: Evidence-based practice (EBP) is the integration of the best research
      evidence with patients' values and clinical circumstances in clinical decision
      making. Teaching of EBP should be evaluated and guided by evidence of its own
      effectiveness. OBJECTIVE: To appraise, summarize, and describe currently
      available EBP teaching evaluation instruments. DATA SOURCES AND STUDY SELECTION:
      We searched the MEDLINE, EMBASE, CINAHL, HAPI, and ERIC databases; reference
      lists of retrieved articles; EBP Internet sites; and 8 education journals from
      1980 through April 2006. For inclusion, studies had to report an instrument
      evaluating EBP, contain sufficient description to permit analysis, and present
      quantitative results of administering the instrument. DATA EXTRACTION: Two raters
      independently abstracted information on the development, format, learner levels,
      evaluation domains, feasibility, reliability, and validity of the EBP evaluation
      instruments from each article. We defined 3 levels of instruments based on the
      type, extent, methods, and results of psychometric testing and suitability for
      different evaluation purposes. DATA SYNTHESIS: Of 347 articles identified, 115
      were included, representing 104 unique instruments. The instruments were most
      commonly administered to medical students and postgraduate trainees and evaluated
      EBP skills. Among EBP skills, acquiring evidence and appraising evidence were
      most commonly evaluated, but newer instruments evaluated asking answerable
      questions and applying evidence to individual patients. Most behavior instruments
      measured the performance of EBP steps in practice but newer instruments
      documented the performance of evidence-based clinical maneuvers or patient-level
      outcomes. At least 1 type of validity evidence was demonstrated for 53% of
      instruments, but 3 or more types of validity evidence were established for only
      10%. High-quality instruments were identified for evaluating the EBP competence
      of individual trainees, determining the effectiveness of EBP curricula, and
      assessing EBP behaviors with objective outcome measures. CONCLUSIONS: Instruments
      with reasonable validity are available for evaluating some domains of EBP and may
      be targeted to different evaluation needs. Further development and testing is
      required to evaluate EBP attitudes, behaviors, and more recently articulated EBP
      skills.

PMID- 16954492
TI  - Changing premed requirements and the medical curriculum.

PMID- 16954493
TI  - High-quality learning for high-quality health care: getting it right.

PMID- 16954494
TI  - Building a diverse physician workforce.

PMID- 16954495
TI  - Self-assessment in lifelong learning and improving performance in practice:
      physician know thyself.

PMID- 16954496
TI  - Medical education 2006: beyond mental mediocrity.

PMID- 16954497
TI  - JAMA patient page. Evidence-based medicine.

PMID- 16954498
TI  - A role for IL-1 receptor antagonist or other cytokines in the acute therapeutic
      effects of IVIg?
AB  - The exact mechanism of action of IVIg in the amelioration of immune
      thrombocytopenic purpura (ITP) is still unclear. Studies have suggested that IVIg
      may function through the regulation of cytokines, including interleukin-1
      receptor antagonist (IL-1Ra), an inhibitor of phagocytosis. Using a mouse model
      relevant to ITP, we confirm an increase in mouse serum levels of IL-1Ra after
      exposure to IVIg, yet a recombinant IL-1Ra did not ameliorate thrombocytopenia.
      IVIg has also been shown to affect the expression of other regulatory cytokines.
      We have also recently established that IVIg specifically targets activating
      FcgammaRs on CD11c+ dendritic cells (DCs) as its primary mechanism of action in
      the amelioration of murine ITP. Herein, we show that IVIg functions
      therapeutically in mice lacking specific cytokines or their receptors that can
      potentially affect DC/macrophage function (IL-1 receptor, IL-4, IL-10, IL-12beta,
      TNF-alpha, IFN-gamma receptor, MIP-1alpha). This suggests that while IVIg may
      mediate the release of a variety of cytokines, the cytokines tested do not
      directly participate in the mechanism of IVIg action.

PMID- 16954499
TI  - Fludarabine increases oxaliplatin cytotoxicity in normal and chronic lymphocytic
      leukemia lymphocytes by suppressing interstrand DNA crosslink removal.
AB  - Oxaliplatin and fludarabine have different but potentially complementary
      mechanisms of action. Previous studies have shown that DNA repair is a major
      target for fludarabine. We postulate that potentiation of oxaliplatin toxicity by
      fludarabine may be due to the inhibition by fludarabine of the activity of the
      DNA excision repair pathways activated by oxaliplatin adducts. To test this, we
      investigated the cytotoxic interactions between the 2 drugs in normal and chronic
      lymphocytic leukemia (CLL) lymphocytes. In each population, the combination
      resulted in greater than additive killing. Analysis of oxaliplatin damage
      revealed that fludarabine enhanced accumulation of interstrand crosslinks (ICLs)
      in specific regions of the genome in both populations, but to a lesser extent in
      normal lymphocytes. The action of fludarabine on the removal of oxaliplatin ICLs
      was explored to investigate the mechanism by which oxaliplatin toxicity was
      increased by fludarabine. Lymphocytes from patients with CLL have a greater
      capacity for ICL unhooking compared with normal lymphocytes. In the presence of
      fludarabine the extent of repair was significantly reduced in both populations,
      more so in CLL. Our findings support a role of fludarabine-mediated DNA repair
      inhibition as a mechanism critical for the cytotoxic synergy of the 2 drugs.

PMID- 16954500
TI  - Reduced expression of inducible gelatinase B/matrix metalloproteinase-9 in
      monocytes from patients with myelodysplastic syndrome: Correlation of inducible
      levels with the percentage of cytogenetically marked cells and with marrow
      cellularity.
AB  - Regulatory molecules produced by stromal cells are often membrane bound until
      cleaved by matrix metalloproteinases (MMPs); cleavage can either activate or
      inactivate regulatory functions. We report here that marrow stromal cells induce
      the expression of MMP-9 in monocytes. Induction was contact independent and could
      be reproduced with recombinant MCP-1/CCL2, whereas IL-6, M-CSF, G-CSF, GM-CSF, IL
      8/CXCL8, SDF-1/CXCL12, and MGSA/CXCL1 did not have this effect. Stroma-induced
      levels of MMP-9 in the monocyte population from healthy donors were relatively
      consistent, whereas induced levels varied significantly (P < .001) in the CD14+
      population from 27 patients with myelodysplastic syndrome (MDS). In patients with
      a clonal chromosomal marker, the level of inducible MMP-9 expression in the
      monocyte population was inversely correlated with the percentage of marker
      positive cells (n = 11, P = .01), suggesting that the ability to induce MMP-9 may
      be compromised in clonally derived monocytes. The inducible levels of MMP-9 were
      also inversely correlated with marrow cellularity observed in biopsies from MDS
      patients (P < .001). We conclude that monocytes can express MMP-9 in response to
      stromal factors and that this response may be significantly decreased in MDS
      derived monocytes.

PMID- 16954501
TI  - CD26 inhibition enhances allogeneic donor-cell homing and engraftment after in
      utero hematopoietic-cell transplantation.
AB  - In utero hematopoietic-cell transplantation (IUHCT) can induce donor-specific
      tolerance to facilitate postnatal transplantation. Induction of tolerance
      requires a threshold level of mixed hematopoietic chimerism. CD26 is a peptidase
      whose inhibition increases homing and engraftment of hematopoietic cells in
      postnatal transplantation. We hypothesized that CD26 inhibition would increase
      donor-cell homing to the fetal liver (FL) and improve allogeneic engraftment
      following IUHCT. To evaluate this hypothesis, B6GFP bone marrow (BM) or enriched
      hematopoietic stem cells (HSCs) were transplanted into allogeneic fetal mice with
      or without CD26 inhibition. Recipients were analyzed for FL homing and peripheral
      blood chimerism from 4 to 28 weeks of life. We found that CD26 inhibition of
      donor cells results in (1) increased homing of allogeneic BM and HSCs to the FL,
      (2) an increased number of injected animals with evidence of postnatal
      engraftment, (3) increased donor chimerism levels following IUHCT, and (4) a
      competitive engraftment advantage over noninhibited congenic donor cells. This
      study supports CD26 inhibition as a potential method to increase the level of FL
      homing and engraftment following IUHCT. The resulting increased donor chimerism
      suggests that CD26 inhibition may in the future be used as a method of increasing
      donor-specific tolerance following IUHCT.

PMID- 16954502
TI  - Hematopoietic stem cell-engrafted NOD/SCID/IL2Rgamma null mice develop human
      lymphoid systems and induce long-lasting HIV-1 infection with specific humoral
      immune responses.
AB  - Critical to the development of an effective HIV/AIDS model is the production of
      an animal model that reproduces long-lasting active replication of HIV-1 followed
      by elicitation of virus-specific immune responses. In this study, we constructed
      humanized nonobese diabetic/severe combined immunodeficiency
      (NOD/SCID)/interleukin-2 receptor gamma-chain knockout (IL2Rgamma(null)) (hNOG)
      mice by transplanting human cord blood-derived hematopoietic stem cells that
      eventually developed into human B cells, T cells, and other monocytes/macrophages
      and 4 dendritic cells associated with the generation of lymphoid follicle-like
      structures in lymphoid tissues. Expressions of CXCR4 and CCR5 antigens were
      recognized on CD4+ cells in peripheral blood, the spleen, and bone marrow, while
      CCR5 was not detected on thymic CD4+ T cells. The hNOG mice showed marked, long
      lasting viremia after infection with both CCR5- and CXCR4-tropic HIV-1 isolates
      for more than the 40 days examined, with R5 virus-infected animals showing high
      levels of HIV-DNA copies in the spleen and bone marrow, and X4 virus-infected
      animals showing high levels of HIV-DNA copies in the thymus and spleen.
      Furthermore, we detected both anti-HIV-1 Env gp120- and Gag p24-specific
      antibodies in animals showing a high rate of viral infection. Thus, the hNOG mice
      mirror human systemic HIV infection by developing specific antibodies, suggesting
      that they may have potential as an HIV/AIDS animal model for the study of HIV
      pathogenesis and immune responses.

PMID- 16954503
TI  - Expression of the human germinal center-associated lymphoma (HGAL) protein
      identifies a subset of classic Hodgkin lymphoma of germinal center derivation and
      improved survival.
AB  - The human germinal-center-associated lymphoma (HGAL) gene and its cognate protein
      are expressed in a germinal center (GC)-specific manner. Its expression in
      classic Hodgkin lymphoma (cHL) prompted us to address whether HGAL expression
      could distinguish biologically distinct subgroups of cHL. Tissue microarrays from
      145 patients treated with curative intent showed HGAL staining in 75% and was
      closely correlated with MUM1/IRF4 (92%) expression. BCL6 (26%), CD10 (0%), BCL2
      (31%), Blimp1 (0.02%), and Epstein-Barr virus (EBV) (20%) showed no specific
      correlation; neither did phospho-STAT6, a key mediator of IL-4 and IL-13
      signaling that induces HGAL and is implicated in cHL pathogenesis. In our study
      cohort, the 5-year overall survival (OS) correlated with young age (less than 45
      years, P < .001), low stage (stage I and II, P = .04), and low International
      Prognostic Score (P = .002). In univariate analysis, HGAL expression was
      associated with improved OS (P = .01) and failure-free survival (FFS) (P = .05)
      but was not independent of other factors in multivariate analysis of OS or FFS.
      The expression of the GC-specific marker HGAL in a subset of cHL suggests that
      these cHLs retain characteristics of GC-derived lymphomas. The association with
      improved OS in univariate but not multivariate analysis suggests that HGAL
      expression is related to known clinical parameters of improved survival.

PMID- 16954504
TI  - INNO-406, a novel BCR-ABL/Lyn dual tyrosine kinase inhibitor, suppresses the
      growth of Ph+ leukemia cells in the central nervous system, and cyclosporine A
      augments its in vivo activity.
AB  - Central nervous system (CNS) relapse accompanying the prolonged administration of
      imatinib mesylate has recently become apparent as an impediment to the therapy of
      Philadelphia chromosome-positive (Ph+) leukemia. CNS relapse may be explained by
      limited penetration of imatinib mesylate into the cerebrospinal fluid because of
      the presence of P-glycoprotein at the blood-brain barrier. To overcome imatinib
      mesylate-resistance mechanisms such as bcr-abl amplification, mutations within
      the ABL kinase domain, and activation of Lyn, we developed a dual BCR-ABL/Lyn
      inhibitor, INNO-406 (formerly NS-187), which is 25 to 55 times more potent than
      imatinib mesylate in vitro and at least 10 times more potent in vivo. The aim of
      this study was to investigate the efficacy of INNO-406 in treating CNS Ph+
      leukemia. We found that INNO-406, like imatinib mesylate, is a substrate for P
      glycoprotein. The concentrations of INNO-406 in the CNS were about 10% of those
      in the plasma. However, this residual concentration was enough to inhibit the
      growth of Ph+ leukemic cells which expressed not only wild-type but also mutated
      BCR-ABL in the murine CNS. Furthermore, cyclosporine A, a P-glycoprotein
      inhibitor, augmented the in vivo activity of INNO-406 against CNS Ph+ leukemia.
      These findings indicate that INNO-406 is a promising agent for the treatment of
      CNS Ph+ leukemia.

PMID- 16954505
TI  - KLF4 suppresses transformation of pre-B cells by ABL oncogenes.
AB  - Genes that are strongly repressed after B-cell activation are candidates for
      being inactivated, mutated, or repressed in B-cell malignancies. Kruppel-like
      factor 4 (Klf4), a gene down-regulated in activated murine B cells, is expressed
      at low levels in several types of human B-cell lineage lymphomas and leukemias.
      The human KLF4 gene has been identified as a tumor suppressor gene in colon and
      gastric cancer; in concordance with this, overexpression of KLF4 can suppress
      proliferation in several epithelial cell types. Here we investigate the effects
      of KLF4 on pro/pre-B-cell transformation by v-Abl and BCR-ABL, oncogenes that
      cause leukemia in mice and humans. We show that overexpression of KLF4 induces
      arrest and apoptosis in the G1 phase of the cell cycle. KLF4-mediated death, but
      not cell-cycle arrest, can be rescued by Bcl-XL overexpression. Transformed
      pro/pre-B cells expressing KLF4 display increased expression of p21CIP and
      decreased expression of c-Myc and cyclin D2. Tetracycline-inducible expression of
      KLF4 in B-cell progenitors of transgenic mice blocks transformation by BCR-ABL
      and depletes leukemic pre-B cells in vivo. Collectively, our work identifies KLF4
      as a putative tumor suppressor in B-cell malignancies.

PMID- 16954506
TI  - Evidence that the JAK2 G1849T (V617F) mutation occurs in a lymphomyeloid
      progenitor in polycythemia vera and idiopathic myelofibrosis.
AB  - The JAK2 V617F mutation has recently been described as an essential oncogenic
      event associated with polycythemia vera (PV), idiopathic myelofibrosis (IMF), and
      essential thrombocythemia. This mutation has been detected in all myeloid
      lineages but has not yet been detected in lymphoid cells. This raises the
      question whether this molecular event occurs in a true lymphomyeloid progenitor
      cell. In this work, we studied the presence of the mutation in peripheral blood
      cells and sorted B, T, and natural killer (NK) cells from PV and IMF. We detected
      the JAK2 V617F mutation in B and NK cells in approximately half the patients with
      IMF and a minority of those with PV. Moreover, in a few cases patients with IMF
      had mutated peripheral T cells. The mutation (homozygous or heterozygous) could
      be subsequently detected in B/NK/myeloid progenitors from PV and IMF, with a much
      higher frequency in clones derived from IMF. Using the fetal thymus organ culture
      (FTOC) assay, the mutation was also detected in all T-cell fractions derived from
      IMF and PV CD34+ cells. These results demonstrate that myeloproliferative
      disorders take their origin in a true myeloid/lymphoid progenitor cell but that
      their phenotype is related to a downstream selective proliferative advantage of
      the myeloid lineages.

PMID- 16954509
TI  - The OECD Health Care Quality Indicators Project: history and background.
AB  - OBJECTIVE: To describe the background, history, and approach of the OECD Health
      Care Quality Indicators (HCQI) Project, an initiative to implement quality
      measures for international benchmarking of medical care at the health system
      level. METHOD: The participating countries and international organizations
      selected five priority areas (cardiac care, diabetes, mental health, patient
      safety, and primary care/prevention) and developed a conceptual framework to
      guide the project. International expert panels were formed to identify clinically
      important, scientifically sound, and feasible measures based on a structured
      consensus process. RESULTS: The consensus process was successfully completed in
      all five priority areas leading to a recommendation of 86 indicators. Nine
      indicators were selected for diabetes, 12 for mental health, 17 for cardiac care,
      21 for patient safety, and 27 for primary care and prevention. CONCLUSIONS: The
      initial experience of the HCQI Project demonstrates that international consensus
      can be achieved in how to measure the quality of care in priority areas,
      suggesting substantial demand for and interest in comparative information at the
      health system level. However, much additional work remains necessary before the
      project can supply policymakers and researchers with ongoing, comprehensive, and
      reliable data on the quality of care in industrialized countries.

PMID- 16954510
TI  - A conceptual framework for the OECD Health Care Quality Indicators Project.
AB  - ISSUES: The Health Care Quality Indicator (HCQI) Project of the Organization for
      Economic Cooperation and Development (OECD), which is aimed at developing a set
      of indicators for comparing the quality of health care across OECD member
      countries, requires a balanced conceptual framework that outlines the main
      concepts and domains of performance that should be captured for the current and
      subsequent phases of the project. ADDRESSING THE ISSUES: This article develops a
      conceptual framework for the OECD's HCQI Project. It first argues that developing
      such a framework should start by addressing the question, 'performance of what
      and to what ends?' We identify at least two different major classes of
      frameworks: (i) health and (ii) health care performance frameworks, both of which
      are in common use. For the HCQI, we suggest a conceptual framework that is
      largely a purposeful modification of the existing performance frameworks and
      which is driven by the health determinants model. CONCLUSIONS: The conceptual
      basis for performance frameworks can be traced back to the health determinants
      model. A health performance framework takes a broader, societal or public health
      view of health determination, whereas a health care performance takes a narrower,
      mostly clinical or technical view of health care in relation to health (needs).
      This article proposes an HCQI framework that focuses on the quality of health
      care, maintains a broader perspective on health and its other determinants, and
      recognizes the key aims of health policy.

PMID- 16954511
TI  - Selecting indicators for patient safety at the health system level in OECD
      countries.
AB  - BACKGROUND: Concerns about patient safety have arisen with growing documentation
      of the extent and nature of harm. Yet there are no robust and meaningful data
      that can be used internationally to assess the extent of the problem and
      considerable methodological difficulties. PURPOSE: This article describes a
      project undertaken as part of the Organization for Economic Cooperation and
      Development (OECD) Quality Indicator Project, which aimed at developing an
      initial set of patient safety indicators. METHODS: Patient safety indicators from
      OECD countries were identified and then rated against three principal criteria:
      importance to patient safety, scientific soundness, and potential feasibility.
      Although some countries are developing multi-source monitoring systems, these are
      not yet mature enough for international exchange. This project reviewed routine
      data collections as a starting point. RESULTS: Of an initial set of 59 candidate
      indicators identified, 21 were selected which cover known areas of harm to
      patients. CONCLUSIONS: This project is an important initial step towards defining
      a usable set of patient safety indicators that will allow comparisons to be made
      internationally and will support mutual learning and quality improvement in
      health care. Measures of harm should be complemented over time with measures of
      effective improvement factors.

PMID- 16954512
TI  - OECD Health Care Quality Indicator Project. The expert panel on primary care
      prevention and health promotion.
AB  - PURPOSE: This article describes a project undertaken as part of the Organization
      for Economic Co-operation and Development (OECD)'s Healthcare Quality Indicator
      (HCQI) Project, which aimed to develop a set of quality indicators representing
      the domains of primary care, prevention and health promotion, and which could be
      used to assess the performance of primary care systems. METHODS: Existing quality
      indicators from around the world were mapped to an organizing framework which
      related primary care, prevention, and health promotion. The indicators were
      judged against the US Institute of Medicine's assessment criteria of importance
      and scientific soundness, and only those which met these criteria and were likely
      to be feasible were included. An initial large set of indicators was reduced by
      the primary care expert panel using a modified Delphi process. RESULTS: A set of
      27 indicators was produced. Six of them were related to health promotion,
      covering health-related behaviours that are typically targeted by health
      education and outreach campaigns, 13 to preventive care with a focus on prenatal
      care and immunizations and eight to primary clinical care mainly addressing
      activities related to risk reduction. The indicators selected placed a strong
      emphasis on the public health aspects of primary care. CONCLUSIONS: This project
      represents an important but preliminary step towards a set of measures to
      evaluate and compare primary care quality. Further work is required to assess the
      operational feasibility of the indicators and the validity of any benchmarking
      data drawn from international comparisons. A conceptual framework needs to be
      developed that comprehensively captures the complex construct of primary care as
      a basis for the selection of additional indicators.

PMID- 16954513
TI  - Selecting indicators for the quality of diabetes care at the health systems level
      in OECD countries.
AB  - PURPOSE: In the context of the Organization for Economic Cooperation and
      Development (OECD) Quality Indicators Project, a set of quality indicators for
      diabetes care was developed, to be used for benchmarking the performance of
      health care systems. BACKGROUND: Diabetes complications markedly reduce quality
      and length of life and are also responsible for enormous health care costs. A
      large body of evidence has shown that several effective treatments and practices
      may substantially reduce this burden. However, a marked variability has been
      documented in preventive and therapeutic approaches, thus suggesting that the
      level of diabetes care currently delivered may not produce the possible health
      related gains. METHODS: Existing quality indicators have been reviewed, with
      particular attention to the work done by the National Diabetes Quality
      Improvement Alliance (NDQIA) in the US. All the measures identified were
      evaluated for their importance, scientific soundness, and feasibility. In
      addition, the panel members selected new distal outcome measures. These measures
      are currently not used in provider comparisons, but they could reveal valuable
      insight into the differential performance of health systems. RESULTS: /b>. Four
      process and two proximal outcome measures were selected among those endorsed by
      the NDQIA. In addition, three new long-term outcome measures have been proposed
      to gain insight into whether and to what degree differences in the processes and
      intermediate outcomes that are captured by the established measures translate
      into better outcomes for patients. CONCLUSIONS: The measures selected can
      contribute to policymakers' and researchers' understanding of differences in the
      quality of diabetes care between health systems. Further work is required to
      assess the availability of reliable and comparable data across OECD countries.

PMID- 16954514
TI  - Quality indicators for international benchmarking of mental health care.
AB  - OBJECTIVE: To identify quality measures for international benchmarking of mental
      health care that assess important processes and outcomes of care, are
      scientifically sound, and are feasible to construct from preexisting data.
      DESIGN: An international expert panel employed a consensus development process to
      select important, sound, and feasible measures based on a framework that balances
      these priorities with the additional goal of assessing the breadth of mental
      health care across key dimensions. PARTICIPANTS: Six countries and one
      international organization nominated seven panelists consisting of mental health
      administrators, clinicians, and services researchers with expertise in quality of
      care, epidemiology, public health, and public policy. Measures. Measures with a
      final median score of at least 7.0 for both importance and soundness, and data
      availability rated as 'possible' or better in at least half of participating
      countries, were included in the final set. Measures with median scores </=3.0 or
      data availability rated as 'unlikely' were excluded. Measures with intermediate
      scores were subject to further discussion by the panel, leading to their adoption
      or rejection on a case-by-case basis. RESULTS: From an initial set of 134
      candidate measures, the panel identified 12 measures that achieved moderate to
      high scores on desired attributes. CONCLUSIONS: Although limited, the proposed
      measure set provides a starting point for international benchmarking of mental
      health care. It addresses known quality problems and achieves some breadth across
      diverse dimensions of mental health care.

PMID- 16954515
TI  - Selecting indicators for the quality of cardiac care at the health system level
      in Organization for Economic Co-operation and Development countries.
AB  - BACKGROUND: Cardiovascular (CV) diseases are major causes of morbidity and death
      in adults in the world. Major differences have been reported in the management
      strategies and the outcome of CV diseases within and between countries. To better
      understand and address these differences, there is a need for quantitative
      information on patient management, outcome, and prognosis. OBJECTIVE: This
      article describes the development of a set of quality indicators for cardiac care
      and summarizes work undertaken by the Cardiac Care Panel of the OECD Health Care
      Quality Indicators Project. METHODS: A list of 61 potential indicators was
      identified through a literature search, review of national measurement systems,
      and nomination from countries participating in the project. The Cardiac Care
      Panel then used a modified Delphi process developed originally by RAND to select
      indicators. Panel members individually rated each indicator on a scale of 1-9 for
      scientific soundness and importance. All indicators receiving scores of 7 or more
      for both importance and soundness were included in the final set. RESULTS:
      Seventeen cardiac indicators were selected for the final set of indicators from
      the following areas: acute coronary syndromes, cardiac interventions, secondary
      prevention, and congestive heart failure. CONCLUSIONS: The final set of 17
      indicators selected by the Cardiac Care Panel constitutes a comprehensive set of
      measures for the most relevant domains of CV care. Nevertheless, gaps remain in
      the area of primary prevention and in particular in areas with rapidly changing
      technology and improving treatment options.

PMID- 16954516
TI  - Beyond the initial indicators: lessons from the OECD Health Care Quality
      Indicators Project and the US National Healthcare Quality Report.
AB  - Interest in comparative quality measurement and evaluation has grown considerably
      over the past two decades because of factors such as the recognition of
      widespread variation in clinical practice, the increased availability of evidence
      about medical effectiveness, and increasing concern about the cost and quality of
      health care. This article describes and contrasts two current efforts to develop
      health performance reporting systems: one, an international initiative-the Health
      Care Quality Indicator (HCQI) Project, sponsored by the Organization for Economic
      Cooperation and Development (OECD); and the other, a national project-the
      National Healthcare Quality Report (NHQR), sponsored by the US Agency for
      Healthcare Quality and Research. There are a number of lessons learned from a
      comparison of the two efforts that are relevant for the future of each project
      and for other indicator-based reporting efforts in quality of health care. These
      lessons are discussed in the article and include: Conceptual frameworks should be
      established to guide the selection of indicators. Choices should be made early on
      in the process to focus on a wide range of clinical conditions or to report on a
      few priority areas. METHODS: should be developed to add and subtract indicators
      while maintaining a stable set of indicators to track over time. Resources should
      be allocated to communication strategies and how best to present data results to
      diverse audiences. Mechanisms should be put in place to maintain project
      momentum.

PMID- 16954517
TI  - Prognostic significance of T-cell or cytotoxic molecules phenotype in classical
      Hodgkin's lymphoma: a clinicopathologic study.
AB  - PURPOSE: Classical Hodgkin's lymphoma (CHL) is characterized by Hodgkin's and
      Reed-Sternberg (H-RS) cells, most of which are derived from germinal-center B
      cells. Nevertheless, one or more markers for T cells and follicular dendritic
      cells (FDC) may be expressed in a minority of H-RS cells in some CHL patients,
      although the clinical significance of this remains controversial. The aim of this
      study was to clarify the association between phenotypic expression and clinical
      outcome in CHL. PATIENTS AND METHODS: Participants were 324 consecutive CHL
      patients, comprising 132 patients with nodular sclerosis (NS), 35 patients with
      NS grade 2 (NS2), and 157 patients with mixed cellularity (MC). We evaluated the
      presenting features and prognosis of patients on categorization into four
      phenotypically defined groups: B-cell (CD20+ and/or CD79a+; n = 63), T-cell
      and/or cytotoxic molecules (CD3+, CD4+, CD8+, CD45RO+, TIA-1+, and/or granzyme
      B+; n = 27), FDC (CD21+ without B-cell marker; n = 22), and null-cell types (n =
      212). Other potential prognostic factors were examined. RESULTS: The T-cell
      and/or cytotoxic molecules group showed a significantly poorer prognosis than the
      other three groups (P < .0001). This finding was seen consistently in
      multivariate analyses. Morphologic subtyping (NS/NS2/MC) and Epstein-Barr virus
      positivity were not identified as independent prognostic factors. CONCLUSION: The
      presence of T-cell and/or cytotoxic antigens in H-RS cells may represent a poor
      prognostic factor in CHL, even if their expression is not regarded as lineage
      specific. Examination of T-cell and/or cytotoxic molecules phenotype in CHL
      patients is recommended as a routine pathologic practice.

PMID- 16954518
TI  - Correlations between O6-methylguanine DNA methyltransferase promoter methylation
      status, 1p and 19q deletions, and response to temozolomide in anaplastic and
      recurrent oligodendroglioma: a prospective GICNO study.
AB  - PURPOSE: To date, no data are available on the relationship between 1p/19q
      deletions and the response to temozolomide (TMZ) in primary anaplastic
      oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) recurrent after
      surgery and standard radiotherapy. The aim of this study was to evaluate
      correlations between 1p/19q deletions, O6-methylguanine DNA methyltransferase
      (MGMT) promoter methylation, and response rate to TMZ in this setting. PATIENTS
      AND METHODS: From June 2000 to February 2005, 67 patients were enrolled; 39
      patients (58%) had AO and 28 patients (42%) had AOA. All patients received 150 to
      200 mg/m2 of TMZ every 28 days. Chromosome 1p and 19q deletions were detected by
      fluorescence in situ hybridization and MGMT promoter methylation was analyzed
      using methylation specific polymerase chain reaction. RESULTS: The overall
      response rate was 46.3% (17 complete responses and 14 partial responses). The
      response rate was higher in patients with AO than in those with AOA (61.5% v 25%,
      P = .003). Combined 1p/19q allelic loss was found in 32 patients (47.8%), while
      MGMT methylation occurred in 37 (68.5%) of 54 assessable patients. 1p/19q loss
      was significantly correlated with response rate (P = .04), time-to-progression (P
      = .003), and overall survival (P = .0001). Despite the significant concordance
      found between MGMT promoter methylation and 1p/19q deletions (P = .02), MGMT
      promoter methylation showed only a borderline correlation with overall survival
      (P = .09). CONCLUSION: TMZ is active in anaplastic oligodendroglial tumors
      treated at first recurrence. In this setting, 1p/19q allelic loss is an important
      predictive and prognostic factor. Further studies on MGMT promoter methylation
      should be performed in randomized trials to test its correlation with survival.

PMID- 16954519
TI  - Molecular correlates of imatinib resistance in gastrointestinal stromal tumors.
AB  - PURPOSE: Gastrointestinal stromal tumors (GISTs) commonly harbor oncogenic
      mutations of the KIT or platelet-derived growth factor alpha (PDGFRA) kinases,
      which are targets for imatinib. In clinical studies, 75% to 90% of patients with
      advanced GISTs experience clinical benefit from imatinib. However, imatinib
      resistance is an increasing clinical problem. PATIENTS AND METHODS: One hundred
      forty-seven patients with advanced, unresectable GISTs were enrolled onto a
      randomized, phase II clinical study of imatinib. Specimens from pretreatment
      and/or imatinib-resistant tumors were analyzed to identify molecular correlates
      of imatinib resistance. Secondary kinase mutations of KIT or PDGFRA that were
      identified in imatinib-resistant GISTs were biochemically profiled for imatinib
      sensitivity. RESULTS: Molecular studies were performed using specimens from 10
      patients with primary and 33 patients with secondary resistance. Imatinib
      resistant tumors had levels of activated KIT that were similar to or greater than
      those typically found in untreated GISTs. Secondary kinase mutations were rare in
      GISTs with primary resistance but frequently found in GISTs with secondary
      resistance (10% v 67%; P = .002). Evidence for clonal evolution and/or polyclonal
      secondary kinase mutations was seen in three (18.8%) of 16 patients. Secondary
      kinase mutations were nonrandomly distributed and were associated with decreased
      imatinib sensitivity compared with typical KIT exon 11 mutations. Using RNAi
      technology, we demonstrated that imatinib-resistant GIST cells remain dependent
      on KIT kinase activity for activation of critical downstream signaling pathways.
      CONCLUSION: Different molecular mechanisms are responsible for primary and
      secondary imatinib resistance in GISTs. These findings have implications for
      future approaches to the growing problem of imatinib resistance in patients with
      advanced GISTs.

PMID- 16954520
TI  - High expression of the ETS transcription factor ERG predicts adverse outcome in
      acute T-lymphoblastic leukemia in adults.
AB  - PURPOSE: In adult T-lymphoblastic leukemia (T-ALL) disease-free survival remains
      limited to 32% to 46%. The adverse prognosis in T-ALL has not been attributed to
      cytogenetic or molecular aberrations. We have determined the prognostic impact of
      the oncogenic transcription factor ERG in T-ALL. PATIENTS AND METHODS: ERG
      expression was analyzed by real-time polymerase chain reaction (PCR) in 105
      adults with newly diagnosed T-ALL treated on the German ALL protocols. Patients
      were dichotomized at ERG's median expression into low (n = 52) and high (n = 53)
      expressers. Homeobox (HOX) 11 and HOX11L2 expression was determined by real-time
      PCR. RESULTS: High ERG expressers compared with low ERG expressers had an
      inferior overall survival (OS, P = .02; 5-year OS: high ERG 26% v low ERG 58%)
      and relapse-free survival (RFS, P = .003; 5-year RFS: high ERG 34% v low ERG
      72%). On multivariable analysis high ERG expression (P = .005), immunophenotypic
      subgroups (early v mature v thymic T-ALL; overall P = .04), HOX11L2 positivity (P
      = .055), and absence of HOX11 (P = .017) were independent adverse risk factors
      predicting RFS. Patients with high ERG expression had a hazard ratio (HR) for
      relapse of 3.2. Within the good prognostic subgroup of thymic T-ALL (n = 57),
      high ERG (HR, 4.1; P = .02) and presence of HOX11L2 (HR, 6.6; P = .008) were
      independent adverse factors for RFS. CONCLUSION: High expression of ERG is an
      adverse risk factor in adult T-ALL. Within thymic T-ALL, otherwise classified as
      standard-risk, high ERG expression-identified patients that were four times more
      likely to fail long-term RFS. The prognostic impact of ERG may assist treatment
      stratification and suggest the need of alternative regimens.

PMID- 16954522
TI  - The power of the anecdote.

PMID- 16954523
TI  - From devastation to integration: Adjusting to and growing from medical trauma.
AB  - Recent trauma research has begun to investigate the possibility of posttraumatic
      growth. However, most studies have investigated posttraumatic growth using
      quantitative methods and thus have neglected people's subjective experience and
      have left unexamined post-traumatic growth in persons with visible impairment. To
      fill some of these gaps, the authors examined the process of recovery and
      posttraumatic growth using a qualitative method. They interviewed 10 participants
      with visible impairment from chronic illness or serious injury using a
      semistructured interview. Using a grounded theory data analysis procedure, the
      authors developed a stage model of trauma and recovery from the interviews. The
      stages that emerged are thematically entitled Apprehension, Diagnosis and
      Devastation, Choosing to Go On, Building a Way to Live, and Integration of the
      Trauma and Expansion of the Self. The authors discuss limitations of the study
      and clinical implications for psychological counseling with this population.

PMID- 16954524
TI  - "The old me could never have done that": how people give meaning to recovery
      following depression.
AB  - Depression is usually a "self-limiting" condition, and recovery is likely, even
      if people do have subsequent episodes. However, despite considerable research
      into depression, little is known about how people actually go about understanding
      and organizing their recovery from depression. In this article, the authors draw
      on one-to-one interviews with people who have experienced mainly severe
      depression to explore the approaches and meanings attributed to overcoming
      depression. They used unstructured and semistructured interview phases to collect
      data and a modified grounded theory approach to analysis. They interviewed 38 men
      and women who had previously experienced depression (selected using the
      principles of maximum variation sampling through general practitioners, support
      groups, and newsletters) in late 2003 and early 2004. The authors explore the
      specific components involved in recovery (e.g., authenticity, responsibility,
      rewriting depression into the self), the stories people tell about their
      recovery, and the strategies deployed to revitalize life following depression.

PMID- 16954525
TI  - Developing a comprehensive understanding of the working alliance in community
      mental health.
AB  - The concept of a working alliance as a key ingredient within therapeutic
      processes has been emphasized by many community mental health researchers and
      practitioners. However, few studies have provided insights into the dimensions
      and operationalization of the concept. To address this gap, the authors analyzed
      data on the working alliance derived from two qualitative data sets: (a)
      interviews conducted with 33 users of community mental health services, family
      members, and service providers; and (b) content extracted from a systematic
      review of 48 articles in the area of community mental health services. Three
      superordinate themes emerged: Building and negotiating trust, I'm on your side,
      and Tools and strategies. The authors discuss implications for community mental
      health practice.

PMID- 16954526
TI  - On a life-saving mission: Nurses' willingness to encounter with intimate partner
      abuse.
AB  - The main purpose of this qualitative study was to explore in depth selected
      expert nurses' experiences of the phenomenon of violence against women and the
      nurses' roles as health care providers to those women. The authors adopted a
      grounded theory method and produced an emerging theory comprising two key themes:
      nurses' personal perceptions toward intimate partner violence and nurses' feeling
      equipped to intervene. The findings showed that violence against women existed in
      a small local community and raised pitfalls caused by nurses' knowing the
      inhabitants. Furthermore, the findings indicate the devotion of nurses and the
      importance of their role in the care of battered women and the sharing of
      knowledge. Thus, the nurses compensate for a lack of training through personal
      maturity and security within the social context.

PMID- 16954527
TI  - Explanatory models of self-understanding in adolescents born with spina bifida.
AB  - The author used phenomenological (interpretive) ethnography to uncover how living
      with physical disability shapes self-understanding (identity) in adolescents born
      with spina bifida. She conducted multiple in-depth interviews with 11 late-stage
      adolescents (ages 18 to 24 years). Analysis of their narrative accounts
      illustrated differences with respect to how study participants understand and
      experience physical disability and its attached meanings in relation to self
      understanding. Study participants took up (claimed) disability in three primary
      ways: identity as overcoming disability, identity as objectifying disability, and
      identity as integrating disability. These informal explanatory models of self
      understanding were fluid, not static, mirroring identity development in youth.
      Findings suggest that individuals born with physical disability confer
      explanatory meaning to their disability that occurs within a background of deeply
      held, taken-for-granted assumptions, meanings, and practices from local and
      larger sociopolitical contexts. These informal explanatory models offer insight
      into positive disability identity.

PMID- 16954528
TI  - The impact of drug use on perceptions of credibility in indigenous outreach
      workers.
AB  - The authors conducted an investigation of perceptions of outreach worker
      credibility using the social network members (N = 20) of indigenous outreach
      workers in an HIV/AIDS prevention intervention. The network members included in
      the study received semistructured interviews following the program's completion.
      Outreach workers who were not actively using illicit drugs were more likely to be
      described as credible than were those who were using drugs. In general, drug use
      negatively affected perceptions of credibility via damaged trust in the outreach
      worker's relationship with his or her network member. Results indicate the
      complexity of using indigenous drug users as outreach workers, the potential
      negative perceptions concerning hypocritical behavior, and the need to evaluate
      social interventions from the standpoint of indirect participants.

PMID- 16954529
TI  - Community perceptions and experiences of domestic violence and induced abortion
      in Wakiso district, Uganda.
AB  - In this qualitative research, the author explored (in general) whether domestic
      violence and induced abortion feature in men's and women's sexual and
      reproductive health experiences. In particular, he explored whether and how
      gender roles influence reproductive decision-making behavior regarding
      contraception, unwanted pregnancy, and induced abortion. The study area was
      Wakiso district in central Uganda, which surrounds the capital city, Kampala. The
      author collected data using in-depth interviews and focus group discussions and
      analyzed them using grounded theory. Effects of unplanned pregnancy were
      perceived to be gender specific. Unintended pregnancy and induced abortion as a
      health issue did not concern men. Rather, what concerned them was spouses'
      contraception, which they often strongly opposed. Consequently, covert
      contraceptive use was common. The author describes a relation between domestic
      violence, nonuse of contraception, unintended pregnancy, and induced abortion.

PMID- 16954530
TI  - Family legacies in shaping teen mothers' caregiving practices over 12 years.
AB  - In this article, the author focuses on the theme of family legacies. The research
      is based on a qualitative study of family caregiving practices in a cohort of
      teenage mothers and their families. Families were first interviewed in 1988-1989
      and reinterviewed in 1993, 1997, and 2001. The author explored continuities and
      turning points in caregiving practices over the 12-year period. Eleven families
      participated at Time 4, including 9 mothers, 3 of their partners, 6 first-born
      children, and 9 grandparents of the children (N = 27). At each time period,
      family caregiving legacies emerged as a salient theme as the mothers and partners
      described their concerns, accomplishments, and the resources for or impediments
      to becoming the parents they wanted to be. Four cases are presented to highlight
      how family legacies were refined, rejected, or modified over time. The author
      also describes implications of the findings for clinical practice and future
      research.

PMID- 16954531
TI  - Finding common ground in team-based qualitative research using the convergent
      interviewing method.
AB  - Research councils, agencies, and researchers recognize the benefits of team-based
      health research. However, researchers involved in large-scale team-based research
      projects face multiple challenges as they seek to identify epistemological and
      ontological common ground. Typically, these challenges occur between quantitative
      and qualitative researchers but can occur between qualitative researchers,
      particularly when the project involves multiple disciplinary perspectives. The
      authors use the convergent interviewing technique in their multidisciplinary
      research project to overcome these challenges. This technique assists them in
      developing common epistemological and ontological ground while enabling swift and
      detailed data collection and analysis. Although convergent interviewing is a
      relatively new method described primarily in marketing research, it compares and
      contrasts well with grounded theory and other techniques. The authors argue that
      this process provides a rigorous method to structure and refine research projects
      and requires researchers to identify and be accountable for developing a common
      epistemological and ontological position.

PMID- 16954532
TI  - A novel family of membrane-bound E3 ubiquitin ligases.
AB  - A novel E3 ubiquitin ligase family that consists of viral E3 ubiquitin ligases
      (E3s) and their mammalian homologues was recently discovered. These novel E3s are
      membrane-bound molecules that share the secondary structure and catalytic domain
      for E3 activity. All family members have two transmembrane regions at the center
      and a RING-CH domain at the amino terminus. Forced expression of these novel E3s
      has been shown to reduce the surface expression of various membrane proteins
      through ubiquitination of target molecules. Initial examples of viral E3s were
      identified in Kaposi's sarcoma associated herpesvirus (KSHV) and murine gamma
      herpesvirus 68 (MHV-68) and have been designated as modulator of immune
      recognition (MIR) 1, 2 and mK3, respectively. MIR 1, 2 and mK3 are able to down
      regulate MHC class I molecule expression, and mK3 is required to establish an
      effective latent viral infection in vivo. The first characterized mammalian
      homologue to MIR 1, 2 and mK3 is c-MIR/MARCH VIII. Forced expression of c
      MIR/MARCH VIII down-regulates B7-2, a co-stimulatory molecule important for
      antigen presentation. Subsequently, several mammalian molecules related to c
      MIR/MARCH VIII have been characterized and named as membrane associated RING-CH
      (MARCH) family. However, the precise physiological function of MARCH family
      members remains as yet unknown.

PMID- 16954533
TI  - Transport of bacterial toxins into target cells: pathways followed by cholera
      toxin and botulinum progenitor toxin.
AB  - A number of bacterial toxins have sophisticated mechanisms for reaching their
      specific targets in mammalian cells, to exert their toxicity. This review focuses
      on the transport mechanisms of cholera toxin and botulinum neurotoxin complex.
      Cholera toxin is an ADP-ribosyltransferase toxin, and the covalent modification
      of heterotrimeric Gs protein in the cytosol leads to the activation of adenylyl
      cyclase and a sequence of events culminating in massive diarrheal disease. Here,
      we describe the structural features of this toxin and the transport pathway
      followed by this toxin from the plasma membrane to the cytosol of intestinal
      epithelial cells. Botulinum neurotoxin is a metalloprotease toxin that enters
      neurons, where it cleaves core proteins of the neuroexocytosis apparatus and
      elicits the inhibition of neurotransmitter release. The food-borne botulism is
      manifested when the neurotoxin is absorbed from the digestive tract, enters the
      blood stream, and reaches the cytosol of the peripheral nerves. We overview the
      structural organization and the long journey followed by this toxin.

PMID- 16954534
TI  - Autophagy in innate immunity against intracellular bacteria.
AB  - Many pathogenic bacteria can invade phagocytic and non-phagocytic cells and
      colonize them intracellularly, then become disseminated to other cells. The
      endocytic degradation pathway is thought to be the only prevention against such
      intracellular pathogens. Autophagy, a fundamental cellular homeostasis pathway
      that operates with the intracellular degradation/recycling system, causes the
      turnover of cellular components by delivering portions of the cytoplasm and
      organelles to lysosomes. Recently, we reported that autophagic degradation is a
      previously unrecognized effector of host innate immunity. Streptococcus pyogenes
      (Group A Streptococcus; GAS) successfully enters human epithelial cells via
      endocytosis. GAS immediately escapes from the endosomes to the cytoplasm and
      gains a replicative niche, after which GAS in the cytoplasm is trapped in
      autophagosome-like compartments and degraded upon fusion with lysosomes. This
      process indicates that autophagy plays a protective role in infectious diseases.
      We also found that autophagic degradation was induced against Staphylococcus
      aureus, while methicillin-resistant S. aureus were resistant to autophagic
      degradation. The present review focuses on the protective function of autophagy
      against bacterial invasion of cells.

PMID- 16954535
TI  - Cross-talk between RNA and prions.
AB  - As concepts evolve in mammalian and yeast prion biology, rather preliminary
      research investigating the interplay between prion and RNA processes are gaining
      momentum. The yeast prion [PSI+] represents an aggregated state of the
      translation termination factor Sup35 resulting in the tendency of ribosomes to
      readthrough stop codons. This "nonsense suppression" activity is investigated for
      its possible physiological role to engender on Saccharomyces cerevisiae the
      ability to respond to stress or variable growth conditions and thereby act as a
      capacitor to evolve. The interaction between prion and RNA is a two way street-
      the cell may have adopted RNA processes in translation to govern the presence of
      prions and the [PSI+] prion's nonsense suppressor phenotype may exhibit different
      growth phenotypes by its control of translation termination. RNA processes in the
      mammalian cell also effect and are affected by prions.

PMID- 16954536
TI  - Structural effects of a covalent linkage between antithrombin and heparin:
      covalent N-terminus attachment of heparin enhances the maintenance of
      antithrombin's activated state.
AB  - We have produced a molecule comprising of permanently-activated covalently linked
      antithrombin and heparin (ATH). This study was designed to elucidate the covalent
      linkage point(s) for heparin on antithrombin and conformational properties of the
      ATH molecule. ATH was produced using Schiff base/Amadori rearrangement by
      incubating antithrombin with unfractionated heparin for 14 d at 40 degrees C. ATH
      was then digested using Proteinase K, and the heparin-peptide was reacted with
      NaIO4/NaBH4/mild acid to degrade the heparin moiety. Sequencing of the remaining
      peptide was performed by Edman degradation with linkage point confirmation by LC
      MS. The degree of insertion of the reactive center loop (RCL) of antithrombin
      into the A-sheet of ATH was examined using synthesized antithrombin RCL peptides.
      Binding between the peptides and ATH, and the formation of ATH in the presence of
      the peptides were tested. CD was used to further examine the secondary and
      tertiary structures of ATH. The results suggest that heparin is conjugated to the
      amino terminal of antithrombin in the majority of ATH molecules, proximal to the
      previously determined heparin binding domain of antithrombin. From the linkage
      data, a model is proposed for the structure of ATH. Studies using the RCL
      peptides and CD analysis of ATH support this model.

PMID- 16954537
TI  - Many novel mammalian microRNA candidates identified by extensive cloning and RAKE
      analysis.
AB  - MicroRNAs are 20- to 23-nucleotide RNA molecules that can regulate gene
      expression. Currently > 400 microRNAs have been experimentally identified in
      mammalian genomes, whereas estimates go up to 1000 and beyond. Here we show that
      many more mammalian microRNAs exist. We discovered novel microRNA candidates
      using two approaches: testing of computationally predicted microRNAs by a
      modified microarray-based detection system, and cloning and sequencing of large
      numbers of small RNAs from different human and mouse tissues. Together these
      efforts experimentally identified 348 novel mouse and 81 novel human microRNA
      candidate genes. Most novel microRNAs candidates are not conserved beyond
      mammals, and ~10% are taxon-specific. Our analyses indicate that the entire
      microRNA repertoire is not remotely exhausted.

PMID- 16954538
TI  - Differential lineage-specific amplification of transposable elements is
      responsible for genome size variation in Gossypium.
AB  - The DNA content of eukaryotic nuclei (C-value) varies approximately 200,000-fold,
      but there is only a approximately 20-fold variation in the number of protein
      coding genes. Hence, most C-value variation is ascribed to the repetitive
      fraction, although little is known about the evolutionary dynamics of the
      specific components that lead to genome size variation. To understand the modes
      and mechanisms that underlie variation in genome composition, we generated
      sequence data from whole genome shotgun (WGS) libraries for three representative
      diploid (n = 13) members of Gossypium that vary in genome size from 880 to 2460
      Mb (1C) and from a phylogenetic outgroup, Gossypioides kirkii, with an estimated
      genome size of 588 Mb. Copy number estimates including all dispersed repetitive
      sequences indicate that 40%-65% of each genome is composed of transposable
      elements. Inspection of individual sequence types revealed differential, lineage
      specific expansion of various families of transposable elements among the
      different plant lineages. Copia-like retrotransposable element sequences have
      differentially accumulated in the Gossypium species with the smallest genome, G.
      raimondii, while gypsy-like sequences have proliferated in the lineages with
      larger genomes. Phylogenetic analyses demonstrated a pattern of lineage-specific
      amplification of particular subfamilies of retrotransposons within each species
      studied. One particular group of gypsy-like retrotransposon sequences, Gorge3
      (Gossypium retrotransposable gypsy-like element), appears to have undergone a
      massive proliferation in two plant lineages, accounting for a major fraction of
      genome-size change. Like maize, Gossypium has undergone a threefold increase in
      genome size due to the accumulation of LTR retrotransposons over the 5-10 Myr
      since its origin.

PMID- 16954539
TI  - Common fragile sites are conserved features of human and mouse chromosomes and
      relate to large active genes.
AB  - Common fragile sites (CFSs) are seen as chromosomal gaps and breaks brought about
      by inhibition of replication, and it is thought that they cluster with tumor
      breakpoints. This study presents a comprehensive analysis using conventional and
      molecular cytogenetic mapping of CFSs and their expression frequencies in two
      mouse strains, BALB/c and C57BL/6, and in human probands. Here we show that
      induced mouse CFSs relate to sites of spontaneous gaps and breaks and that CFS
      expression levels in chromosome bands are conserved between the two mouse strains
      and between syntenic mouse and human DNA segments. Furthermore, four additional
      mouse CFSs were found to be homologous to human CFSs on the molecular cytogenetic
      level (Fra2D-FRA2G, Fra4C2-FRA9E, Fra6A3.1-FRA7G, and Fra6B1-FRA7H), increasing
      the number of such CFSs already described in the literature to eight. Contrary to
      previous reports, DNA helix flexibility is not increased in the 15 human and
      eight mouse CFSs molecularly defined so far, compared to large nonfragile control
      regions. Our findings suggest that the mechanisms that provoke instability at
      CFSs are evolutionarily conserved. The role that large transcriptionally active
      genes may play in CFS expression is discussed.

PMID- 16954540
TI  - Inference of population genetic parameters in metagenomics: a clean look at messy
      data.
AB  - Metagenomic projects generate short, overlapping fragments of DNA sequence, each
      deriving from a different individual. We report a new method for inferring the
      scaled mutation rate, theta = 2Neu, and the scaled exponential growth rate, R =
      Ner, from the site-frequency spectrum of these data while accounting for
      sequencing error via Phred quality scores. After obtaining maximum likelihood
      parameter estimates for theta and R, we calculate empirical Bayes quality scores
      reflecting the posterior probability that each apparently polymorphic site is
      truly polymorphic; these scores can then be used for other applications such as
      SNP discovery. For realistic parameter ranges, analytic and simulation results
      show our estimates to be essentially unbiased with tight confidence intervals. In
      contrast, choosing an arbitrary quality score cutoff (e.g., trimming reads) and
      ignoring further quality information during inference yields biased estimates
      with greater variance. We illustrate the use of our technique on a new project
      analyzing activated sludge from a lab-scale bioreactor seeded by a wastewater
      treatment plant.

PMID- 16954541
TI  - MicroRNAs and other small RNAs enriched in the Arabidopsis RNA-dependent RNA
      polymerase-2 mutant.
AB  - The Arabidopsis genome contains a highly complex and abundant population of small
      RNAs, and many of the endogenous siRNAs are dependent on RNA-Dependent RNA
      Polymerase 2 (RDR2) for their biogenesis. By analyzing an rdr2 loss-of-function
      mutant using two different parallel sequencing technologies, MPSS and 454, we
      characterized the complement of miRNAs expressed in Arabidopsis inflorescence to
      considerable depth. Nearly all known miRNAs were enriched in this mutant and we
      identified 13 new miRNAs, all of which were relatively low abundance and
      constitute new families. Trans-acting siRNAs (ta-siRNAs) were even more highly
      enriched. Computational and gel blot analyses suggested that the minimal number
      of miRNAs in Arabidopsis is approximately 155. The size profile of small RNAs in
      rdr2 reflected enrichment of 21-nt miRNAs and other classes of siRNAs like ta
      siRNAs, and a significant reduction in 24-nt heterochromatic siRNAs. Other
      classes of small RNAs were found to be RDR2-independent, particularly those
      derived from long inverted repeats and a subset of tandem repeats. The small RNA
      populations in other Arabidopsis small RNA biogenesis mutants were also examined;
      a dcl2/3/4 triple mutant showed a similar pattern to rdr2, whereas dcl1-7 and
      rdr6 showed reductions in miRNAs and ta-siRNAs consistent with their activities
      in the biogenesis of these types of small RNAs. Deep sequencing of mutants
      provides a genetic approach for the dissection and characterization of diverse
      small RNA populations and the identification of low abundance miRNAs.

PMID- 16954542
TI  - Chromosome Conformation Capture Carbon Copy (5C): a massively parallel solution
      for mapping interactions between genomic elements.
AB  - Physical interactions between genetic elements located throughout the genome play
      important roles in gene regulation and can be identified with the Chromosome
      Conformation Capture (3C) methodology. 3C converts physical chromatin
      interactions into specific ligation products, which are quantified individually
      by PCR. Here we present a high-throughput 3C approach, 3C-Carbon Copy (5C), that
      employs microarrays or quantitative DNA sequencing using 454-technology as
      detection methods. We applied 5C to analyze a 400-kb region containing the human
      beta-globin locus and a 100-kb conserved gene desert region. We validated 5C by
      detection of several previously identified looping interactions in the beta
      globin locus. We also identified a new looping interaction in K562 cells between
      the beta-globin Locus Control Region and the gamma-beta-globin intergenic region.
      Interestingly, this region has been implicated in the control of developmental
      globin gene switching. 5C should be widely applicable for large-scale mapping of
      cis- and trans- interaction networks of genomic elements and for the study of
      higher-order chromosome structure.

PMID- 16954543
TI  - CT coronary angiography: where does it fit?

PMID- 16954544
TI  - Molecular position of radiolabels and its impact on functional integrity of
      proteins.

PMID- 16954545
TI  - Thyroid stunning revisited.

PMID- 16954546
TI  - The so-called stunning of thyroid tissue.
AB  - When thyroid tissues exhibited concentrations of therapeutic (131)I that appeared
      to be less than that predicted by data from the preceding diagnostic (131)I, the
      phenomenon was called stunning. We hypothesized that stunning arose from the
      early effects of the therapeutic dose of (131)I and that the initial uptake of
      (131)I, observed within the first day, was not impaired by the diagnostic dose.
      METHODS: The hypothesis was tested by 2 types of studies. In each type, the
      fractional concentrations of (131)I in residual neck thyroid tissues of patients
      with papillary thyroid carcinoma were quantified. In the first study, fractional
      concentrations of diagnostic and therapeutic (131)I were measured at 2 d, a time
      when stunning has been observed, and expressed as ratios of radioactivity:
      therapeutic/diagnostic (Rx/Dx). Three different doses of diagnostic (131)I were
      prescribed to assess a dose response. In the second study, patients were
      prospectively recruited and tested to record disappearances of radioactivity from
      thyroid tissues. Diagnostic doses were 1.0 mCi (37 MBq) in all; therapeutic doses
      were 150 and 30 mCi (5,550 and 1,110 MBq), each to half of the patients. The
      disappearance curves were extrapolated to the period between 0 and 1 d, an
      interval when maximum uptake of ingested (131)I would be expected. The fractional
      concentrations of (131)I at 2 d and at 0-1 d were compared in terms of Rx/Dx
      ratios to assess changes at each time point. RESULTS: In the first study, after
      diagnostic doses of 2, 1, and 0.5 mCi (74, 37, and 18.5 MBq), mean 2-d Rx/Dx
      values in 24, 29, and 17 patients were 0.35, 0.50, and 0.46 (P = 0.087). Of all
      patients, 74% exhibited Rx/Dx <0.6. In the second study, 6 of 10 patients
      exhibited disappearance curves of (131)I in which Rx/Dx was <0.6 at 2 d; 5 of the
      6 had Rx/Dx values >0.97 at the 0- to 1-d point. In 1 patient the Rx/Dx was 0.54
      at 2 d and 0.66 at the earlier time point. The other 4 patients had disappearance
      curves in which Rx/Dx values were >1.0 throughout or were above 0.6 and did not
      greatly change. CONCLUSION: Two days after the administration of (131)I, the mean
      fractional concentration of radioactivity in thyroid tissues after a therapeutic
      dose is <60% of the diagnostic dose in most patients, but no correlation of Rx/Dx
      with the mCi in the diagnostic dose was seen. In 5 of 6 patients in whom the
      Rx/Dx at 2 d was <0.6, the maximum fractional concentrations of therapeutic and
      diagnostic (131)I (i.e., the tissue uptakes during the first day) were similar;
      this pattern was most apparent after therapies with 150 mCi. These results
      support the hypothesis that "stunning" of thyroid tissues, often observable by 2
      d, is primarily the consequence of early destructive effects from therapeutic
      (131)I.

PMID- 16954547
TI  - Effect of diabetes mellitus on sympathetic neuronal regeneration studied in the
      model of transplant reinnervation.
AB  - The transplanted heart is initially denervated but undergoes subsequent
      sympathetic reinnervation. It thus provides a unique model for studying
      regeneration as a specific component of autonomic nerve biology. The aim of this
      study was to determine the effect of diabetes mellitus on the regenerational
      capacity of sympathetic neurons using molecule-targeted PET. METHODS: Twenty-two
      nonrejecting, otherwise healthy cardiac transplant recipients underwent PET with
      the (11)C-labeled physiologic neurotransmitter epinephrine at 4.0 +/- 3.3 y after
      surgery. Sympathetic reinnervation was defined as regional restoration of
      epinephrine retention to values within normal limits. RESULTS: Reinnervation was
      observed in 8 of 12 patients with no evidence of diabetes and in 6 of 10 patients
      with a long-term history of diabetes mellitus. The regional extent of
      reinnervation (4.7% +/- 5.3% of left ventricle vs. 19.1% +/- 20.6% for
      nondiabetic recipients, P = 0.04) and the regeneration rate (0.8% +/- 1.0% of
      left ventricle per year vs. 8.0% +/- 10.1% for nondiabetic recipients, P = 0.04)
      were significantly reduced in diabetic subjects. In a multivariate model,
      diabetes mellitus was an independent determinant of allograft reinnervation.
      Finally, the reappearance of innervation was found to correlate with an improved
      chronotropic and inotropic response to stress in a standardized, symptom-limited
      exercise test including radionuclide angiography. CONCLUSION: The regenerational
      capacity of the sympathetic nervous system of the heart is reduced, but not
      abolished, by diabetes mellitus. This study on cardiac transplant recipients
      further supports a general link between impaired glucose handling and cardiac
      autonomic nerve function.

PMID- 16954548
TI  - Repeatability of cold pressor test-induced flow increase assessed with H(2)(15)O
      and PET.
AB  - The aim of this study was to evaluate the repeatability of endothelium-related
      myocardial blood flow (MBF) responses to cold pressor testing (CPT) as assessed
      by PET. METHODS: In 10 age-matched control subjects (26.6 +/- 3.4 y) and 10
      tobacco smokers (24.9 +/- 3.3 y) MBF was assessed at rest and after repeated CPT
      (CPT1 and CPT2, 40 min apart) using PET with H(2)(15)O. CPT was performed by a 2
      min immersion of the subject's foot in ice water. MBF values were corrected for
      cardiac workload (rate.pressure product), and the repeatability of CPT-related
      MBF values was assessed according to Bland and Altman. RESULTS: Corrected MBF at
      CPT1 and CPT2 were comparable in control subjects (1.79 +/- 0.37 vs. 1.70 +/-
      0.35 mL/min/g; P = not significant [NS]) and in smokers (1.97 +/- 0.42 vs. 1.80
      +/- 0.41 mL/min/g; P = NS). Repeatability coefficients in control subjects and
      smokers were 0.46 mL/min/g (27% of the mean MBF) and 0.51 mL/min/g (27%),
      respectively. MBF increased significantly after CPT in both groups but tended to
      be lower in smokers (P = 0.08). CONCLUSION: PET measured MBF combined with CPT is
      a feasible and repeatable method for the evaluation of endothelium-related
      changes of MBF.

PMID- 16954549
TI  - Evaluation of in vivo P-glycoprotein function at the blood-brain barrier among
      MDR1 gene polymorphisms by using 11C-verapamil.
AB  - P-glycoprotein (P-gp) is a membrane protein that functions as an adenosine
      triphosphate-dependent efflux pump for xenobiotics at the blood-brain barrier
      (BBB). Polymorphisms of MDR1 gene have been reported to be associated with the
      expression level of P-gp. (11)C-Verapamil is considered to be one of the suitable
      radioligands for evaluating P-gp functions. However, the metabolites of verapamil
      might complicate the quantitative analysis because of their possible brain
      penetration. In the present study, we investigated the P-gp functional
      differences at the BBB between the haplotypes (1236TT, 2677TT, 3435TT vs. 1236CC,
      2677GG, 3435CC) of the MDR1 gene with different quantitative analyses of (11)C
      verapamil. METHODS: Thirty-three healthy male volunteers were enrolled in this
      study after identification of the haplotypes of the MDR1 gene. Brain PET scans
      with (11)C-verapamil were performed for 16 min. Integration plot analysis, which
      yields brain uptake clearance, was performed with the first 3-min data.
      Integration plot analysis was then compared with several other quantitative
      analyses with 16-min data (1-input, 1-tissue compartment model, and the area
      under the curve ratio (AUC(ratio)) between brain and plasma). RESULTS: In the
      integration plot, there was no difference in the absolute values of brain uptake
      clearance (CL(uptake)) between the haplotypes; CL(uptake) of (11)C-verapamil for
      the haplotypes (1236TT, 2677TT, 3435TT vs. 1236CC, 2677GG, 3435CC) were 0.053 +/-
      0.011 and 0.051 +/- 0.011 mL/g/min, respectively. CL(uptake) of (11)C-verapamil
      in the integration plot was significantly correlated with K1 and DV(K1/k2) (DV is
      distribution volume; K1 and k2 are plasma and tissue rate constants) in the 1
      input, 1-tissue compartment model and the AUC(ratio). CONCLUSION: On the basis of
      the several quantitative analyses of (11)C-verapamil, the assumption that the
      function of P-gp at the BBB is different between the haplotypes (3 single
      nucleotide polymorphisms: C1236T, G2677T, and C3435T) of MDR1 gene was not
      supported.

PMID- 16954550
TI  - Integrin receptor imaging of breast cancer: a proof-of-concept study to evaluate
      99mTc-NC100692.
AB  - The present study was a proof-of-concept study to provide an initial indication
      of the efficacy and safety of imaging malignant breast tumors using (99m)Tc
      NC100692. The agent is a small peptide with high affinity for integrin receptors
      that are upregulated and expressed preferentially on proliferating endothelial
      cells. METHODS: Sixteen patients with suggestive mammographic findings and 4
      patients with benign lesions were included. The "standard of truth" was based on
      the histopathologic diagnosis of the recruited patients. All subjects received up
      to 75 microg of (99m)Tc-NC100692 with an average (99m)Tc activity of 694 MBq
      (range, 561-747 MBq). Safety endpoints were treatment-emergent adverse events
      (AEs) and changes in a limited physical examination, electrocardiogram (ECG)
      recordings, blood biochemistry, hematology, coagulation, vital signs, and urine
      analysis after administration of (99m)Tc-NC100692 and throughout the 24-h follow
      up. Static images and SPECT were acquired between 40 min and 2.5 h after
      injection of the agent. Two experienced nuclear medicine physicians read the
      images in a nonblinded fashion. RESULTS: Nineteen of 22 malignant lesions were
      detected using (99m)Tc-NC100692 scintigraphy. Twenty lesions confirmed as
      malignant by histopathology were seen on mammography or ultrasound. Two
      additional lesions were identified from histopathology alone. Safety parameters
      evaluated through the follow-up period of 2.5 h included clinical laboratory
      tests, vital signs, and ECG. Five of 20 subjects experienced nonserious AEs, and
      all AEs were classified as mild. One subject experienced an AE (dysgeusia)
      possibly related to administration of (99m)Tc-NC100692. This AE was mild and
      lasted only for a few minutes. No deaths, serious AEs, or withdrawals due to AEs
      occurred during the study. CONCLUSION: Nineteen of 22 malignant lesions (86%)
      were clearly detected via scintigraphic imaging after administration of (99m)Tc
      NC100692. Overall, the efficacy data in subjects with suspected breast lesions
      suggest that (99m)Tc-NC100692 scintigraphy may be effective in detecting
      malignant lesions. The use of (99m)Tc-NC100692 in subjects with breast cancer is
      safe and well tolerated. Further studies are warranted to assess the clinical
      potential of (99m)Tc-NC100692.

PMID- 16954551
TI  - Dual time point 18F-FDG PET imaging detects breast cancer with high sensitivity
      and correlates well with histologic subtypes.
AB  - This prospective study was designed to assess the utility of the dual time point
      imaging technique by (18)F-FDG PET in detecting primary breast cancer and to
      determine whether there is a relationship between (18)F-FDG uptake and its change
      over time and the histopathologic subtypes. METHODS: One hundred fifty-two
      patients with newly diagnosed breast cancer underwent 2 sequential PET scans
      (dual time point imaging) for preoperative staging. The maximum standardized
      uptake value (SUVmax) of (18)F-FDG was measured from both time points. The
      percent change in SUVmax (Delta%SUVmax) between time points 1 (SUVmax1) and 2
      (SUVmax2) was calculated. Patients were divided into 2 groups according to
      histopathology as invasive and noninvasive. Invasive tumors were also divided
      into 2 groups (>10 mm and 4-10 mm). The tumor-to-contralateral normal breast
      (background) ratios of SUVmax at both time points for groups were measured and
      the Delta%SUVmax values were calculated. RESULTS: The mean +/- SD of the SUVmax1,
      the SUVmax2, and the Delta%SUVmax were 3.9 +/- 3.7, 4.3 +/- 4.0, and 8.3% +/-
      11.5% for invasive; 2.0 +/- 0.6, 2.1 +/- 0.6, and 3.4% +/- 13.0% for noninvasive;
      and were 1.2 +/- 0.3, 1.1 +/- 0.2, and -10.0% +/- 10.8% for the contralateral
      normal breast groups, respectively. In the comparison of SUVmax1, Delta%SUVmax,
      and the tumor-to-background ratios among groups, all results were significant (P
      < 0.001). Visual assessment revealed that the sensitivity of dual time point
      imaging was 90.1% for invasive cancer >10 mm, 82.7% for invasive breast cancers 4
      10 mm, and 76.9% for noninvasive breast cancers. CONCLUSION: Dual time point
      imaging is a simple and noninvasive method that may improve the sensitivity and
      accuracy of (18)F-FDG PET in assessing patients with primary breast cancer. The
      changes that are noted in SUVs in dual time point imaging vary depending on the
      histopathologic type of primary breast cancer.

PMID- 16954552
TI  - Differential roles of 18F-FDG PET in patients with locoregional advanced
      nasopharyngeal carcinoma after primary curative therapy: response evaluation and
      impact on management.
AB  - This prospective study compares the efficacies of whole-body (18)F-FDG PET and a
      conventional work-up (CWU) in evaluating the treatment response for patients with
      locoregional advanced nasopharyngeal carcinoma (NPC) after primary curative
      therapy and investigates the impact of PET on patient management. METHODS:
      Patients who had locoregional advanced NPC (stages III and IVa-b, staged by (18)F
      FDG PET and CWU) and who had completed primary curative therapy for 3 mo were
      enrolled. The curative therapy consisted of concurrent chemoradiotherapy with or
      without induction chemotherapy. All of the patients also underwent (18)F-FDG PET
      and CWU to evaluate the response. The criteria for final diagnosis were based on
      pathology or subsequent follow-up for at least 6 mo. Rates of detection by (18)F
      FDG PET and CWU and the impact on management were determined on site and patient
      bases, respectively. RESULTS: From January 2002 to August 2005, 131 patients with
      NPC were eligible, including 71 patients with stage III NPC (group A) and 60
      patients with stage IVa-b NPC (group B). Twelve patients were proven to have
      residual tumors. (18)F-FDG PET had a higher overall sensitivity than CWU in group
      A (100% vs. 25%) and group B (91.7% vs. 58.3%). The overall specificity of PET
      was significantly higher than that of CWU in group B (97.6% vs. 91.7%; P = 0.019)
      but was slightly lower in group A (95.7% vs. 96.7%). The overall accuracy of PET
      also was significantly higher than that of CWU in group B (97.2% vs. 89.4%; P =
      0.002) but was similar to that of CWU in group A (95.8% vs. 95.3%). PET resulted
      in management changes in 11 patients (15.4%; 11/71) in group A, with positive and
      negative impacts on 3 and 8 patients, respectively. In group B, the management of
      26 of 60 patients (43%) was changed as a result of PET and included positive
      impacts on 23 patients and negative impacts on 3 patients. CONCLUSION: (18)F-FDG
      PET plays differential roles in patients with stage III NPC and stage IVa-b NPC
      after primary curative therapy. PET has higher sensitivity and specificity in
      evaluating the response and results in better management of patients with stage
      IVa-b NPC. PET has a less prominent impact on patient management but higher
      sensitivity in patients with stage III NPC.

PMID- 16954553
TI  - Can fluorodihydroxyphenylalanine PET replace somatostatin receptor scintigraphy
      in patients with digestive endocrine tumors?
AB  - The aim of this study was to evaluate whether (18)F-fluorodihydroxyphenylalanine
      ((18)F-FDOPA) PET is accurate for the diagnosis and follow-up of any type of well
      differentiated digestive endocrine tumor and to assess its performance compared
      with standard somatostatin receptor scintigraphy (SRS) using (111)In
      pentetreotide. METHODS: We reviewed the results of 33 evaluable (18)F-FDOPA PET
      and (111)In-pentetreotide SRS examinations performed between March 2002 and
      September 2005 in 30 patients referred for documented well-differentiated
      digestive endocrine tumor. RESULTS: The sensitivity and accuracy of (18)F-FDOPA
      PET were significantly better for carcinoid tumors (defined according to the
      World Health Organization 2000 classification) (n = 19) than for noncarcinoid
      tumors (n = 14)-that is, 93% versus 25% for sensitivity (P < 0.01) and 89% versus
      36% for accuracy (P < 0.01), respectively. In contrast, the performances of
      (111)In-pentetreotide SRS did not differ according to the carcinoid or
      noncarcinoid type of the primary endocrine tumor-that is, 81% versus 75% for
      sensitivity and 79% versus 71% for accuracy, respectively. In carcinoid tumors,
      comparison between (18)F-FDOPA PET and (111)In-pentetreotide SRS showed that
      (18)F-FDOPA PET more accurately evaluated the extent of disease than (111)In
      pentetreotide SRS. (111)In-Pentetreotide SRS did not reveal any additional
      lesions in any case. Conversely, in noncarcinoid tumors, the extent of the
      disease was more accurately evaluated in all cases by (111)In-pentetreotide SRS
      than by (18)F-FDOPA PET. CONCLUSION: This preliminary study emphasizes the
      importance of a precise histologic characterization of well-differentiated
      digestive endocrine tumor to select the best radiopharmaceutical. (18)F-FDOPA PET
      appears to be useful in carcinoid tumors and could become the first-line
      scintigraphic imaging modality for these tumors, but (111)In-pentetreotide SRS
      appeared to be a better first-line scintigraphic imaging modality for
      noncarcinoid digestive tumors.

PMID- 16954554
TI  - Effect of sequential administration of an opioid and cholecystokinin on
      gallbladder ejection fraction: brief communication.
AB  - This study was undertaken to test the effect of sequential administration of an
      opioid and intravenous cholecystokinin (CCK) on gallbladder ejection fraction.
      METHODS: Forty-nine patients who had received an opioid underwent quantitative
      cholescintigraphy with octapeptide of CCK (CCK-8). Gallbladder ejection fraction
      and CCK-8-induced paradoxical filling were calculated. RESULTS: In the basal
      state, more of the hepatic bile entered the gallbladder (67%) than the small
      intestine (33%). After CCK-8 infusion, gallbladder ejection fraction was low in
      37 (76%) of 49 patients and normal in 12 (24%). All 5 types of opioids lowered
      ejection fraction. CCK-induced paradoxical filling of the gallbladder was noted
      in 7 patients, but only one showed paradoxical filling of greater than 20% and
      none had a normal gallbladder ejection fraction. The lowering effect of opioids
      on gallbladder ejection fraction may last as long as 18 h after intake.
      CONCLUSION: CCK-8 produced a normal gallbladder ejection fraction in 24% of
      patients who had received an opioid and thus could exclude both acute and chronic
      cholecystitis during a single hepatobiliary study.

PMID- 16954555
TI  - Dosimetry in Peptide radionuclide receptor therapy: a review.
AB  - The potential of targeted therapy with radiolabeled peptides has been reported in
      several clinical trials. Although there have been many improvements in dose
      estimation, a general and reliable dosimetric approach in peptide receptor
      radionuclide therapy (PRRT) is still a matter of debate. This article reviews the
      methods for PRRT dosimetry and the results presented in the literature.
      Radiopharmaceutical characteristics, data processing, dosimetric outcomes, and
      methods to protect critical organs are reported. The biological effective dose,
      based on the linear quadratic model, is also described.

PMID- 16954556
TI  - Patient-specific dosimetry calculations using mathematic models of different
      anatomic sizes during therapy with 111In-DTPA-D-Phe1-octreotide infusions after
      catheterization of the hepatic artery.
AB  - The aim of the study was to provide dosimetric data on intrahepatic (111)In
      diethylenetriaminepentaacetic acid (DTPA)-D-Phe(1)-octreotide therapy for
      neuroendocrine tumors with overexpression of somatostatin receptors. METHODS: A
      dosimetric protocol was designed to estimate the absorbed dose to the tumor and
      healthy tissue in a course of 48 treatments for 12 patients, who received a mean
      activity of 5.4 +/- 1.7 GBq per session. The patient-specific dosimetry
      calculations, based on quantitative biplanar whole-body scintigrams, were
      performed using a Monte Carlo simulation program for 3 male and 3 female
      mathematic models of different anatomic sizes. Thirty minutes and 2, 6, 24, and
      48 h after the radionuclide infusion, blood-sample data were collected for
      estimation of the red marrow radiation burden. RESULTS: The mean absorbed doses
      per administered activity (mGy/MBq) by the critical organs liver, spleen,
      kidneys, bladder wall, and bone marrow were 0.14 +/- 0.04, 1.4 +/- 0.6, 0.41 +/-
      0.08, 0.094 +/- 0.013, and (3.5 +/- 0.8) x 10(-3), respectively; the tumor
      absorbed dose ranged from 2.2 to 19.6 mGy/MBq, strongly depending on the lesion
      size and tissue type. CONCLUSION: The results of the present study quantitatively
      confirm the therapeutic efficacy of transhepatic administration; the tumor-to
      healthy-tissue uptake ratio was enhanced, compared with the results after
      antecubital infusions. Planning of treatment was also optimized by use of the
      patient-specific dosimetric protocol.

PMID- 16954557
TI  - Locoregional delivery of adenoviral vectors.
AB  - The overall median survival of patients with a malignant glioma is <1 y. Because
      malignant gliomas rarely metastasize outside the skull, locoregional treatment
      strategies, such as gene therapy, are under investigation. Recently, convection
      enhanced delivery (CED) has been presented as a method to improve delivery of
      large molecules. The goal of this study was to evaluate whether CED improves
      intratumoral delivery of adenoviral vectors and compare it with single injection
      (SI) and multiple injection (4x, MI). METHODS: A replication-deficient adenoviral
      vector encoding the herpes simplex virus thymidine kinase (HSV-tk) and the human
      somatostatin receptor subtype 2 (sst(2)) was administered into nude mice bearing
      subcutaneous U87 xenografts. Tumors were injected with 1.5 x 10(9) plaque-forming
      units of Ad5.tk.sstr by CED, SI, or MI. Three days later, [(99m)Tc-N(4)(0
      1),Asp(0),Tyr(3)]octreotate ((99m)Tc-Demotate 2) was injected intravenously to
      monitor the virus-induced sst(2) expression. gamma-Camera imaging was performed
      for in vivo imaging, and the tumor uptake of (99m)Tc-Demotate 2 was determined by
      gamma-counter. Furthermore, the tumor was sectioned and ex vivo autoradiography
      was performed. After decay of radioactivity, adjacent sections were submitted to
      in vitro autoradiography with (125)I-DOTA-Tyr(3)-octreotate, which was used to
      calculate the transduced areas. RESULTS: Transfected xenograft tissues showed
      high sst(2) expression and were clearly visualized with a gamma-camera.
      Accumulation of radioactivity was 2-fold higher in the tumors that were injected
      with MI compared with CED and SI (P = 0.01). CED and SI resulted in equal uptake
      of radioactivity in the tumors. The measured areas of transduction in ex vivo and
      in vitro autoradiographs showed a high concordance (r(2) = 0.89, P < 0.0001). The
      maximum area of transfection was significantly larger after MI than after CED (P
      < 0.05) or SI (P = 0.05). Also, the measured volume of distribution was twice as
      high after administration of Ad5.tk.sstr by MI (56.6 mm(3)) compared with SI
      (25.3 mm(3)) or CED (26.4 mm(3)). CONCLUSION: CED does not increase adenoviral
      vector distribution in a glioma xenograft model compared with SI. Therefore, in
      the clinic MI is probably the most effective delivery method for the large
      adenoviral particle (70 nm) in malignant gliomas.

PMID- 16954558
TI  - Dependence of cardiac 11C-meta-hydroxyephedrine retention on norepinephrine
      transporter density.
AB  - The norepinephrine analog (11)C-meta-hydroxyephedrine (HED) is used with PET to
      map the regional distribution of cardiac sympathetic neurons. HED is rapidly
      transported into sympathetic neurons by the norepinephrine transporter (NET) and
      stored in vesicles. Although much is known about the neuronal mechanisms of HED
      uptake and retention, there is little information about the functional
      relationship between HED retention and cardiac sympathetic nerve density. The
      goal of this study was to characterize the dependence of HED retention on nerve
      density in rats with graded levels of cardiac denervation induced chemically with
      the neurotoxin 6-hydroxydopamine (6-OHDA). METHODS: Thirty male Sprague-Dawley
      rats were divided into 6 groups, and each group was administered a different dose
      of 6-OHDA: 0 (controls), 7, 11, 15, 22, and 100 mg/kg intraperitoneally. One day
      after 6-OHDA injection, HED (3.7-8.3 MBq) was injected intravenously into each
      animal and HED concentrations in heart and blood at 30 min after injection were
      determined. Heart tissues were frozen and later processed by tissue
      homogenization and differential centrifugation into a membrane preparation for in
      vitro measurement of cardiac NET density. A saturation binding assay using (3)H
      mazindol as the radioligand was used to measure NET density (maximum number of
      binding sites [B(max)], fmol/mg protein) for each heart. RESULTS: In control
      animals, NET B(max) was 388 +/- 23 fmol/mg protein and HED heart uptake (HU) at
      30 min was 2.89% +/- 0.35 %ID/g (%ID/g is percentage injected dose per gram
      tissue). The highest 6-OHDA dose of 100 mg/kg caused severe cardiac denervation,
      decreasing both NET B(max) and HED HU to 8% of their control values. Comparing
      values for all doses of 6-OHDA, HED retention had a strong linear correlation
      with NET density: HU = 0.0077B(max) -0.028, r(2) = 0.95. CONCLUSION: HED
      retention is linearly dependent on NET density in rat hearts that have been
      chemically denervated with 6-OHDA, suggesting that HED retention is a good
      surrogate measure of NET density in the rat heart. This finding is discussed in
      relation to clinical observations of the dependence of HED retention on cardiac
      nerve density in human subjects using PET.

PMID- 16954559
TI  - Noninvasive imaging of atherosclerotic lesions in apolipoprotein E-deficient and
      low-density-lipoprotein receptor-deficient mice with annexin A5.
AB  - Transgenic mice such as apolipoprotein E-deficient (apoE(-/-)) and low-density
      lipoprotein receptor-deficient (LDLR(-/-)) mice exhibit hypercholesterolemia and
      develop complex atherosclerotic lesions similar to those seen in humans.
      Radiolabeled annexin A5 has been successfully used to noninvasively image
      experimental and clinical atherosclerotic disease. We evaluated the feasibility
      of annexin A5 imaging in transgenic apoE(-/-) and LDLR(-/-) mice with or without
      a cholesterol diet. METHODS: Thirty-three mice (mean age, 62 +/- 0.9 wk old) were
      used. Of these 33 mice, apoE(-/-) mice with the cholesterol diet for 4 mo (n = 5)
      and without the cholesterol diet (n = 8) and LDLR(-/-) mice with the cholesterol
      diet for 6 mo (n = 7) and without the cholesterol diet (n = 7) were compared with
      6 normal wild-type (C57BL/6) mice with the same genetic background. (99m)Tc
      annexin A5 was injected in 31 animals for noninvasive imaging using micro
      SPECT/CT. After in vivo micro-SPECT/CT, aortas were explanted to acquire ex vivo
      images and calculate the percentage injected dose per gram (%ID/g) annexin
      uptake, followed by histologic and immunohistochemical characterization. For the
      evaluation of precise target localization, biotinylated annexin A5 was injected
      in the remaining 2 normally fed apoE(-/-) mice. RESULTS: Aortic lesions were
      clearly visualized noninvasively by micro-SPECT and aorta calcification was
      detectable by micro-CT. The quantitative uptake of annexin A5 was highest in the
      cholesterol-fed apoE(-/-) (0.88 +/- 0.27 %ID/g) mice, followed by the normal chow
      fed apoE(-/-) (0.60 +/- 0.16 %ID/g), the cholesterol-fed LDLR(-/-) (0.59 +/- 0.14
      %ID/g), the chow-fed LDLR(-/-) (0.40 +/- 0.31 %ID/g), and the control (0.15 +/-
      0.05 %ID/g) mice. The histologic extent of atherosclerosis paralleled radiotracer
      uptake, and immunohistochemical studies revealed a significant correlation
      between radiotracer uptake and both macrophage infiltration and the extent of
      apoptosis. Intravenously injected biotinylated annexin A5 localized in apoptotic
      and nonapoptotic macrophages. CONCLUSION: This study demonstrates the feasibility
      of noninvasive imaging of atherosclerosis with radiolabeled annexin A5 in
      transgenic mouse models of human atherosclerosis.

PMID- 16954560
TI  - Troponin I overexpression inhibits tumor growth, perfusion, and vascularization
      of morris hepatoma.
AB  - Antiangiogenic gene transfer inhibiting growth of new blood vessels is a
      promising approach in cancer therapy. Human troponin I (TnI) efficiently inhibits
      endothelial cell proliferation, migration, as well as angiogenesis and tumor
      growth in vivo. However, little is known about its effects on perfusion and tumor
      biology. METHODS: Stable Morris hepatoma (MH3924A) cells overexpressing human TnI
      (TnI-MH3924A) were cocultured with human umbilical vein endothelial cells
      (HUVECs) followed by measurements of endothelial apoptosis and proliferation.
      Furthermore, tumor growth and perfusion were determined using H(2)(15)O and
      (68)Ga-DOTA-albumin (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''
      tetraacetic acid) PET as well as functional MRI. Additionally, histologic
      measurements of vascularization, apoptosis, proliferation, and gene array
      analyses were performed. RESULTS: Apoptosis of HUVECs was increased and
      proliferation was decreased after coculture with TnI-MH3924A cells. TnI-MH3924A
      tumors showed a significant inhibition of growth (90%) and a decreased perfusion
      (25%), whereas blood volume remained unchanged. MRI investigations demonstrated a
      significant decrease of the rate constant k(ep). Immunohistochemical analyses
      showed decreased microvessel density and proliferation and significant induction
      of apoptosis. Furthermore, TnI-expressing hepatomas demonstrated changes in the
      expression of genes related to angiogenesis, apoptosis, signal transduction, or
      stress. CONCLUSION: TnI regulates tumor growth by modulating vascularization
      including apoptosis induction and decrease of proliferation. In addition, changes
      in expression of genes associated with angiogenesis, apoptosis, signal
      transduction, or stress were found. The upregulation of angiogenesis and stress
      related genes indicates a cross-talk of different mechanisms as part of the
      tumor's reaction to TnI. Because the decrease of vascularization led to lower
      perfusion values as measured by PET and MRI, these noninvasive methods are
      promising tools for the monitoring of antiangiogenic gene therapy.

PMID- 16954561
TI  - Angiopoietin-2 overexpression in morris hepatoma results in increased tumor
      perfusion and induction of critical angiogenesis-promoting genes.
AB  - Monitoring of angiogenesis-relevant approaches with functional imaging and
      histomorphometric analyses is desirable to evaluate the biologic effects. In this
      study we wished to examine the complex effects of angiopoietin-2 (Ang-2) gene
      transfer in a rat hepatoma model. METHODS: Using a bicistronic retroviral vector
      for Ang-2, Morris hepatoma (MH3924A) cell lines with Ang-2 expression were
      generated (Ang-2-MH3924A). In human umbilical vein endothelial cells (HUVECs)
      cocultured with Ang-2-MH3924A, the proliferative action with or without growth
      factors were determined. Furthermore, animal experiments were performed to
      measure effects on tumor growth and perfusion. Finally, tumors were examined by
      immunohistochemistry and DNA chip analysis. RESULTS: Ang-2-expressing MH3924A
      enhanced basic fibroblast growth factor-mediated endothelial cell proliferation.
      Perfusion, as measured by H(2)(15)O PET, was increased in genetically modified
      tumors. Consistent with the increased perfusion, micro- and macrovascularization
      were increased. However, tumor growth was similar to wild-type MH3924A (WT
      MH3924A). Proliferating cell nuclear antigen and TUNEL (terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labeling) staining revealed an increased
      number of positive cells, indicating a compensation of increased proliferation by
      enhanced apoptosis. DNA chip analysis showed an induction of angiogenesis
      promoting genes, including crucial vascular growth factor receptors, as well as
      genes related to extracellular matrix (ECM), apoptosis, signal transduction, and
      oxidative stress. CONCLUSION: Our results suggest that Ang-2 expression increases
      perfusion or vascularization, especially in interaction with the vascular growth
      factor system, without affecting tumor growth. Simultaneous, enhanced expression
      of genes for ECM, apoptosis, and signal transduction indicates Ang-2's versatile
      role in angiogenesis including its destabilizing function on ECM and endothelium.

PMID- 16954562
TI  - Tumor 18F-FDG incorporation is enhanced by attenuation of P53 function in breast
      cancer cells in vitro.
AB  - Mutations in the p53 gene, often resulting in loss of wild-type (WT) p53
      expression, are found at high frequencies in several cancer types. High uptake of
      (18)F-FDG detected using (18)F-FDG PET has been associated with a poor prognosis.
      To determine whether high (18)F-FDG uptake may be related to decreased expression
      of WT p53, we examined (18)F-FDG uptake in cells transfected with dominant
      negative p53 constructs that abrogate WT p53 function. METHODS: Two clones of MCF
      7 breast cancer cells were stably transfected with a dominant negative p53
      construct. (18)F-FDG uptake, hexokinase (HK) activity, and glucose transport were
      measured in each clone and in the control WT cells from which the clones had been
      derived. The expression of glucose transporters, HKs, and glucose-6-phosphatase
      was determined using microarray technology. RESULTS: Microarray experiments
      revealed that glucose transporters 1, 8, and 10 were expressed in MCF-7 cells,
      whereas glucose-6-phosphatase was absent. HK I was the principal HK in MCF-7
      cells but was not differentially expressed at the messenger RNA level in the
      dominant negative p53 clones, compared with WT cells. However, increased HK
      activity was observed in both dominant negative p53 clones, compared with WT MCF
      7. (18)F-FDG uptake was increased in both clones expressing the dominant negative
      p53 constructs. CONCLUSION: These data suggest that abrogation of p53 in breast
      cancer is associated with specific changes in glucose metabolism detected by PET.

PMID- 16954563
TI  - Quantitative analysis of 11C-verapamil transfer at the human blood-brain barrier
      for evaluation of P-glycoprotein function.
AB  - P-glycoprotein in the blood-brain barrier (BBB) has been found to be associated
      with several types of neurologic damage. (11)C-Verapamil has been used for in
      vivo imaging of P-glycoprotein function in the BBB by PET, but metabolites in
      plasma complicate the quantitative analysis of human studies. In this study, we
      validated the quantification methods of (11)C-verapamil transfer from plasma to
      the brain in humans. METHODS: The transfer rate constant from plasma to the
      brain, K(1), was estimated by nonlinear least squares (NLS) with a 2-input
      compartment model, including the permeation of the main metabolite in plasma at
      the BBB, and with a 1-input compartment model using only 15-min data that
      contained little metabolite in plasma. K(1) was also estimated by graphical
      analysis of an integration plot that uses only early-time data, before the
      appearance of metabolites, and the estimated K(1) was compared with that obtained
      by the NLS method. In the simulation study, the reliability of parameter
      estimates in the graphical analysis method was investigated for various values of
      rate constants, time ranges of parameter estimations, and noise levels. RESULTS:
      (11)C-Verapamil in plasma gradually converted to its metabolites, and about 45%
      of the radioactivity in the plasma specimen was associated with (11)C-verapamil
      metabolites at 30 min after injection. Although K(1) estimated from graphical
      analysis was slightly smaller than that by NLS, there was strong correlation
      among the K(1) values obtained by these 3 methods. In the simulation study, for
      graphical analysis, the differences between the true and mean of K(1) estimates
      became larger and the coefficient of variation (COV) of K(1) estimates became
      smaller as the end time of linear regression became later. The COV of graphical
      analysis was almost equal to that of NLS with the 1-input compartment model.
      CONCLUSION: The transfer of (11)C-verapamil from plasma to the brain was able to
      be quantitatively estimated by graphical analysis because this method can provide
      K(1) from the data of the initial few minutes without considering the effect of
      the metabolites in plasma.

PMID- 16954564
TI  - Early response of sigma-receptor ligands and metabolic PET tracers to 3 forms of
      chemotherapy: an in vitro study in glioma cells.
AB  - The significant presence of nontumor cell populations within tumors can
      complicate the assessment of in vivo tumor metabolism during therapy. To more
      clearly define the impact of cytotoxic agents, we compared early changes in the
      uptake of 6 PET tracers in cultured glioma cells. Doxorubicin (1 micromol/L),
      cisplatin (10 micromol/L), and 5-fluorouracil (10 mmol/L) were selected to target
      different aspects of cellular metabolism. METHODS: The tracers were 2
      extracellular sigma-receptor ligands, (18)F-FE-SA5845 (nonsubtype selective) and
      (11)C-SA4503 (sigma-1), the nucleoside 3'-deoxy-3'-(18)F-fluorothymidine ((18)F
      FLT), (11)C-choline, (11)C-methionine, and (18)F-FDG. C6 glioma cells were grown
      as monolayers and exposed to cytotoxic agents at concentrations at least 1 order
      of magnitude higher than the concentration for 50% growth inhibition of this cell
      line. Effects on cellular parameters were measured after 0, 1, 2, 3, 4, and 24 h.
      RESULTS: All treatments resulted in a decline in cell numbers within 24 h. The
      binding of the sigma-ligands (11)C-SA4503 and (18)F-FE-SA5845 and the uptake of
      (11)C-choline (normalized for the number of viable cells) were strongly
      increased. The uptake of (18)F-FDG showed little change, and cellular
      accumulation of (18)F-FLT and (11)C-methionine was decreased. Uptake of (18)F-FLT
      and (11)C-methionine was related to the fraction of cells in S-phase, but not
      under all conditions: (a) doxorubicin caused a more rapid decline in (18)F-FLT
      uptake than in the S-phase fraction because of depletion of cellular adenosine
      triphosphate, and (b) cisplatin inhibited the transport of (11)C-methionine
      across the tumor cell membrane. CONCLUSION: Increased binding of sigma-ligands
      and an increased uptake of (11)C-choline after chemotherapy may reflect active
      membrane repair in damaged cells. (18)F-FLT and (11)C-methionine behaved as
      proliferation markers. However, the accumulation of (18)F-FDG reflected not the
      proliferation rate but, rather, the number of viable cells per well.

PMID- 16954565
TI  - Improved detection of cell death in vivo with annexin V radiolabeled by site
      specific methods.
AB  - Labeled annexin V is widely used to detect cell death in vitro and in vivo.
      Nearly all studies have been done with annexin V derivatized via amine-directed
      bifunctional agents; it was thought that these molecules retained full
      bioactivity compared with unmodified protein. We now show that this assumption is
      incorrect by measuring the affinity of annexin V for cells in vitro by
      quantitative calcium titration under conditions of low membrane occupancy.
      METHODS: Annexin V was modified with 4 different amine-directed agents: the N
      hydroxysuccinimide esters of hydrazinonicotinic acid, mercaptoacetyltriglycine,
      and biotin; and with fluorescein isothiocyanate. RESULTS: In all cases, the
      membrane-binding affinity was decreased by derivatization, even at very low
      average stoichiometries. A statistical model based on the Poisson distribution
      accurately predicted the observed heterogeneity of derivatization as a function
      of average derivatization stoichiometry. This model also showed that multiply
      derivatized forms, which are the ones most likely to have compromised
      bioactivity, contributed disproportionately to the binding and imaging signals.
      The in vitro binding assay correctly predicted in vivo uptake in a mouse liver
      model of apoptosis for all proteins tested. The annexin V-128 protein, labeled at
      a single specific site at the N terminus, showed twice as much apoptosis-specific
      liver uptake as did all forms of annexin V derivatized randomly via amino groups.
      CONCLUSION: The membrane-binding activity of annexin V is much more sensitive to
      amine-directed chemical modification than previously realized. New annexin V
      molecules labeled by site-specific methods will greatly improve sensitivity for
      detecting cell death in vivo.

PMID- 16954566
TI  - 18F-FDG PET of thyroid nodules with inconclusive cytologic results.

PMID- 16954568
TI  - Adequate evaluation of image registration in hybrid PET/CT.

PMID- 16954572
TI  - Assessing undergraduate laboratory performance.
AB  - The lab notebook is one element for assessing student laboratory performance.
      However, it is also important to be able to communicate research results in a
      journal article format and a visual poster format. Another key aspect to
      scientific research is the ability to present a research plan. This article
      describes four assessment tools that can be used in conjunction with
      undergraduate lab courses that provide the opportunity for the students to
      practice each of these essential communication skills.

PMID- 16954573
TI  - Differentiation of PC12 cells.
AB  - This 3-week-long series of collaborative laboratory exercises explores how to use
      a cultured cell system (PC12 cells) to study signaling pathways involved in
      cellular differentiation. The laboratory would be useful in a neurobiology or
      cell biology course for advanced undergraduate students. The background and
      details for performing the lab are provided along with suggestions for assessing
      student performance and understanding.

PMID- 16954574
TI  - Clinical outcomes with drug-eluting stents following atheroablation therapies.
AB  - BACKGROUND: Prior studies of atheroablation (directional atherectomy, rotational
      atherectomy and laser angioplasty) have demonstrated either no advantage or worse
      outcomes relative to conventional balloon angioplasty. Because these techniques
      are still required in a minority of patients, we hypothesized that the use of
      drug-eluting stents (DES) would minimize the rate of major adverse cardiac events
      (MACE) after atheroablation. METHODS: From 2,252 percutaneous coronary
      intervention procedures, 212 patients were extracted using case control matching
      and were analyzed to compare the rate of MACE across four groups (DES with
      atheroablation, bare-metal stent (BMS) with atheroablation, DES without
      atheroablation, bare-metal stent without atheroablation). A Cox proportional
      hazards model was constructed to determine predictors of MACE after adjustment
      for potential confounders. Internal validation was performed with bootstrapping.
      RESULTS: There were 36 patients, 42 patients, 63 patients and 71 patients in each
      of the groups, respectively. The incidence of 30-day and 6-month MACE was
      numerically lowest among patients who received DES after atheroablation, although
      the differences did not reach statistical significance (30-day MACE: 0% DES with
      atheroablation, 4.8% BMS with atheroablation, 3.2% DES without atheroablation,
      8.5% BMS without atheroablation; 6-month MACE: 2.8% DES with atheroablation,
      19.0% BMS with atheroablation, 6.4% DES without atheroablation, 16.9% BMS without
      atheroablation). After adjustment, the use of atheroablation was not a predictor
      of MACE. CONCLUSIONS: This study suggests that in situations where directional
      atherectomy, rotational atherectomy or laser angioplasty is required to optimize
      stenting, the use of DES can minimize MACE associated with atheroablation.

PMID- 16954575
TI  - Temporal trends in target vessel revascularization in clinical practice: long
      term outcomes following coronary stenting from the Duke Database for
      Cardiovascular Disease.
AB  - OBJECTIVE: We examined outcomes of clinical restenosis and temporal trends in
      repeat target vessel revascularization (TVR) among a broad, unselected patient
      population undergoing percutaneous coronary revascularization. BACKGROUND: The
      extent to which clinical trials involving protocol-specified follow-up
      angiography reflect real-world practice where interventions are driven by
      clinical restenosis is not completely understood. Whether clinical outcomes have
      varied over a long-term period that has paralleled substantial advances in stent
      design, balloon delivery catheter and adjunctive pharmacologic therapies is
      uncertain. METHODS: To characterize the effectiveness of coronary stenting in
      routine practice, we examined 1-year clinical outcomes of death and repeat TVR
      among 5,765 patients enrolled in the Duke Database for Cardiovascular Disease who
      underwent stent placement between 1994 and 2002. To assess for temporal trends in
      outcomes, patients were further divided into tertiles according to the year of
      initial revascularization. RESULTS: Overall, the 1-year occurrence of TVR and
      death was 11.4% and 4.9%, respectively. Rates of repeat TVR increased at 3-month
      intervals, with most events occurring prior to 9 months. In an adjusted analysis
      over an 8-year period, 1-year survival did not significantly differ across
      patient tertiles (p = 0.95), although rates of recurrent TVR significantly
      decreased (1994-1996, 11.1%; 1997-1999, 11.5%; 2000-2002, 9.3%; p = 0.003).
      CONCLUSIONS: In a broad patient population in whom repeat angiography is not
      protocol-specified, most events occur within the initial months following
      revascularization, yet late clinical restenosis continues. Although survival has
      not improved since the introduction of coronary stents, overall rates of repeat
      revascularization have modestly, but significantly, declined.

PMID- 16954576
TI  - Bare metal stents: no longer passe?

PMID- 16954577
TI  - Impact of drug-eluting stents on outcomes of patients with end-stage renal
      disease undergoing percutaneous coronary revascularization.
AB  - BACKGROUND AND OBJECTIVE: End-stage renal disease (ESRD) patients on chronic
      dialysis are at heightened risk for target vessel revascularization (TVR) after
      coronary stenting. However, ESRD patients were excluded from the trials that
      demonstrated the superiority of drug-eluting stents (DES) over bare metal stents
      (BMS) in reducing TVR. We sought to identify the impact of stent type (DES versus
      BMS) on TVR and other cardiac adverse events in ESRD patients. METHODS: The study
      included 89 consecutive ESRD patients who underwent coronary stenting and were
      followed for greater than or equal to 9 months. TVR was the primary endpoint, and
      the secondary endpoint was a composite of death, myocardial infarction (MI) and
      TVR. Multivariate logistic regression models were used to adjust for differences
      in clinical and procedural characteristics. RESULTS: DES were used in 24 and BMS
      in 65 patients. The stent diameter was smaller (p = 0.008), but the stent length
      was longer (p = 0.006) in the DES group. TVR was required in 1 (4%) of DES and 17
      (26%) BMS patients, while 8 (33%) DES and 39 (60%) BMS patients met the secondary
      endpoint. By multivariate logistic regression, DES use was associated with a
      significant reduction in TVR (OR 0.07, 95% CI 0.006-0.844; p = 0.036) and a
      significant reduction in death, MI and TVR (OR 0.11, 95% CI 0.022-0.513; p =
      0.005). CONCLUSION: A high rate of ischemic events was noted for ESRD patients,
      regardless of stent type. However, in ESRD patients undergoing coronary
      revascularization, DES use is effective in reducing 9-month TVR and the composite
      of death, MI and TVR.

PMID- 16954578
TI  - End-stage renal disease and drug-eluting stents: one small step forward.

PMID- 16954579
TI  - Coronary angiography and angioplasty using the aberrant radial artery as an
      access site.
AB  - OBJECTIVE: To study the suitability of the aberrant radial artery (ARA) as an
      access site for coronary angiography and angioplasty. BACKGROUND: In certain
      situations, the radial artery operator finds that the right radial artery in its
      usual location is unsuitable for a transradial procedure (TRP). In such cases,
      the ARA should be considered as an alternate access site. METHODS: Between
      January 2002 and December 2004, all patients considered suitable for a TRP with a
      clinically absent radial artery, or a small radial artery and a palpable ARA,
      underwent a TRP using this vessel as an access site. We describe the technical
      aspects and the differences that this approach entails, in comparison to the
      standard radial artery approach to TRPs. RESULTS: Of the 3,610 patients
      considered suitable for a TRP, 22 patients underwent 29 procedures using the ARA
      as an access site [22 angiograms and 7 percutaneous transluminal coronary
      angioplasty procedures (PTCAs)]. The median age of the patients was 55 years,
      with 19 males and 3 females. All procedures using the aberrant radial artery were
      successful. None of the patients developed spasm or an access site complication.
      The mean fluoroscopy time for angiography in the right radial artery group was
      4.6 minutes, and 4.8 minutes for the ARA group. The procedure timed were 24
      minutes and 32 minutes, respectively. CONCLUSION: The aberrant radial artery can
      be used as a safe alternate access site for coronary angiography and angioplasty
      when the right radial artery at the usual site is not suitable.

PMID- 16954580
TI  - Eptifibatide-eluting stent as an antiproliferative and antithrombotic agent: in
      vitro evaluation.
AB  - OBJECTIVE: Stent thrombosis and in-stent restenosis remain problematic despite
      drug-eluting stents (DES), especially in diabetic patients and in those with
      small-vessel disease. Eptifibatide inhibits the platelet glycoprotein IIb/IIIa
      and smooth muscle cell (SMC) avb3 receptor, thus potentially influencing both
      thrombosis and proliferation. The aim of the present studies was to examine the
      absorption and elution characteristics of eptifibatide on polymer-coated stents
      and investigated their effect on SMC proliferation, platelet deposition and
      platelet aggregation in vitro. METHODS AND RESULTS: Polymer-mixed eptifibatide
      and H3-labeled eptifibatide were loaded onto bare metal stents. A maximum of 111
      mcg of eptifibatide was loaded onto 3.0 x 18 mm stents. Drug elution
      characteristics were tested in a PBS perfusion circuit. Elution profile consisted
      of an early rapid phase (24% +/- 0.03 loss over 1 hour) followed by a sustained
      release with 44% +/- 2.30 still present on the stent after 30 days. Eluted
      eptifibatide significantly inhibited adenosine diphosphate (ADP)-induced platelet
      aggregation by 95% +/- 0.70 (p < 0.01). Efficacy of stents eluting eptifibatide
      for antiplatelet effect was determined by measuring deposition of 111indium
      labeled platelets on stents. Platelet deposition was significantly reduced by 48%
      +/- 6 in comparison to controls (p = 0.0065). Finally, drug-loaded stents were
      placed in SMC culture and showed a distinct zone of cell growth inhibition within
      1 mm2 (88 +/- 22 vs. 208 +/- 23 SMCs in control), and within 2 mm2 of stent (131
      +/- 32 vs. 191 +/- 23 SMCs in control) (both p < 0.01). CONCLUSIONS: Eptifibatide
      can be successfully loaded onto stents. It elutes in a predictable manner,
      significantly inhibiting platelet deposition, aggregation and SMC proliferation
      in vitro. These studies pave the way to developing stent-based delivery of a
      potent antiplatelet agent, which additionally may inhibit SMC activity.

PMID- 16954581
TI  - Polymer stent coating for prevention of neointimal hyperplasia.
AB  - AIMS: Restenosis has been the principal limitation of bare metal stents. Based
      upon the presumption that platelet and inflammatory cell recruitment initiate
      neointimal proliferation, we explored a novel polymer coating that reduces cell
      stent interactions. The purpose of the present study was to investigate the
      effect of poly(L-lysine)-graft-poly(ethyleneglycol) (PLL-g-PEG) adsorbed to stent
      surfaces to reduce neointimal hyperplasia in the porcine restenosis model.
      METHODS AND RESULTS: Seven animals were instrumented each with 2 stainless steel
      stents (15 mm length, 2.5-3.5 mm diameter), randomly implanted in 1 major
      epicardial coronary artery. One stent was dip-coated with PLL-g-PEG, whereas the
      other stent served as the uncoated control stent. All animals were sacrificed
      after 6 weeks for histological examination. Neointimal hyperplasia was
      significantly less (-51%) in the PLL-g-PEG-coated stents (1.15 +/- 0.59 mm2) than
      in the uncoated control stents (2.33 +/- 1.01 mm2; p < 0.001). Conversely, lumen
      size was larger in the PLL-g-PEG-coated stents (2.91 +/- 1.17 mm2) than in the
      uncoated stents (2.04 +/- 0.64 mm2; p < 0.001). High magnification
      histomorphologic examination revealed no signs of inflammation or thrombus
      formation in either stent group. CONCLUSIONS: Polymeric steric stabilization of
      stents with PLL-g-PEG significantly reduces neointimal hyperplasia in the porcine
      restenosis model. Reduction of cell-stent interactions mediated by PLL-g-PEG
      appear to improve biocompatibility of stainless steel stents without evidence of
      adverse inflammatory or prothrombotic effects.

PMID- 16954583
TI  - Directional coronary atherotomy - experimental use of single-blade cutting
      balloon.
AB  - BACKGROUND: In the drug-eluting stent era, minimum stent diameter is one
      independent predictor of restenosis. Some plaque modification is necessary before
      stenting to obtain the minimum stent diameter, but plaque modification using
      current devices is difficult in certain lesions, such as those in eccentric small
      vessels. As a potential solution to this problem, we investigate the usefulness
      of a single-blade Cutting Balloon (SCB) in this study. METHODS: We used the SCB
      in 5 porcine coronary arteries (2 LAD, 1 LCx and 2 RCA) to investigate the
      feasibility of directional atherotomy. We also tried the kissing balloon
      technique (KBT) with the SCB in 3 bifurcations from the same arteries. We used
      intravascular ultrasound (IVUS) guidance to position and direct the atherotome
      using the side holes of the guiding catheter as a marker. We also assessed plaque
      modification with IVUS before and after percutaneous coronary intervention and
      took coronary sections to inspect tissue pathology after the procedures. RESULTS:
      In all 5 porcine models, we were able to view and confirm the success and
      accuracy of our incision on IVUS. We were successfully able to control the
      direction of the blade without balloon rupture during KBT. We were also able to
      verify the directional incisions afterwards from examination of tissue pathology.
      CONCLUSION: Our investigation suggests that this SCB may be used effectively for
      directional atherotomy. We can accurately modify the plaque with this device by
      correctly positioning the blade to choose the direction of the incision. The next
      challenge is to improve the reliability of the device and to move on to in vivo
      trials.

PMID- 16954584
TI  - Coronary atherectomy: a revisit with a new tool: single-blade cutting balloon.

PMID- 16954585
TI  - Successful percutaneous closure of a patent foramen ovale causing hypoxia in the
      setting of an elevated hemidiaphragm due to Guillian-Barre syndrome.

PMID- 16954586
TI  - Alcohol septal ablation for hypertrophic obstructive cardiomyopathy: novel
      application of the cutting balloon.

PMID- 16954587
TI  - Percutaneous interventions of acute left main occlusions may be necessary.

PMID- 16954588
TI  - Too late, too complex, but.

PMID- 16954589
TI  - Thrombotic occlusion of a drug-eluting stent - is IVUS mandatory.
AB  - Acute stent thrombosis is a rare but serious complication of stent implantation.
      Although anecdotal reports suggest that the use of drug-eluting stents (DES) may
      increase the risk of stent thrombosis, this has not been borne out in randomized,
      controlled trials. We report a case of acute stent thrombosis following
      implantation of a DES, with review of the literature. Despite the initial
      favorable procedural result, the patient developed stent thrombosis 7 days later;
      intravascular ultrasound (IVUS) demonstrated incomplete deployment of the stent.
      We recommend the use of IVUS in the management of acute stent thrombosis in order
      to exclude incomplete stent expansion which may underlie acute thrombotic
      occlusion.

PMID- 16954590
TI  - Single coronary ostium - a right coronary artery arising from the left main
      coronary artery.
AB  - Single coronary ostium is a very rare congenital anomaly with an incidence of
      0.024% in angiographic series. This is the third case of Shirani-Roberts subtype
      IB4: solitary ostium in the left coronary sinus associated with a retroaortic
      coursing right coronary artery that arises from the left main coronary artery.
      The patient is a 45-year-old male with no past medical history, and who was seen
      in the clinic for evaluation of a murmur. Echocardiography showed rheumatic heart
      disease with mild mitral regurgitation and moderate aortic regurgitation; no
      shunts were present. Coronary and aortic root angiography did not show a vessel
      originating from the right coronary cusp. The right coronary artery originated
      from the left main coronary artery and had an aberrant course which was dorsal to
      the ascending aorta. No associated congenital heart disease was present.

PMID- 16954591
TI  - Transluminal removal of an embolized venous catheter fragment with coronary
      angioplasty tools.
AB  - Central venous catheterization has become an important technique for the
      diagnosis and management of patients requiring intensive medical care. The use of
      devices to perform this procedure has been accompanied by a corresponding
      increase in complications. The embolization of foreign bodies to the venous
      system is not a rare event. This is a report on the transluminal effective and
      relatively easy removal of a sheath fragment from the right ventricle using
      standard angioplasty tools.

PMID- 16954592
TI  - Blunt microdissection and rotational atherectomy: an effective combination for
      the resistant chronic total occlusion.
AB  - Percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) has a
      lower success rate than nontotal occlusions. Like nontotal coronary occlusions,
      successful procedural outcomes of CTOs confers improvement in clinical outcomes.
      Reasons for unsuccessful PCI of CTOs may stem from various steps of the procedure
      including failure to cross the occlusion with a guidewire or a balloon, or
      failure to adequately dilate or modify the lesion. The Frontrunner blunt
      microdissection device is designed to improve the odds of guidewire passage
      through coronary occlusions, whereas the Rotablator rotational atherectomy device
      is intended for plaque modification, especially in resistant, elastic or calcific
      lesions. The Frontrunner and Rotablator can each facilitate the procedure at
      their respective junctures; the combined use of these technologies can enhance
      the overall PCI success rates, especially regarding difficult CTOs. This case
      presentation encounters two technical challenges: the inability of the balloon
      catheter to cross the CTO, and the inability to recross the occlusion with the
      less favorable RotaWire. In this case, the combined use of the Frontrunner and
      Rotablator devices was necessary to achieve overall procedural success. When
      tackling difficult CTOs, a comprehensive strategy that encompasses multiple
      devices and technologies can enable ultimate procedural success.

PMID- 16954593
TI  - Emergent percutaneous intervention with a drug-eluting stent of a cabrol graft-to
      left main anastomosis during a non-ST-elevation infarction in a patient with
      Marfan's syndrome.

PMID- 16954594
TI  - Mechanical circulatory support in fulminant myocarditis: case report with brief
      review and use of novel anterograde limb perfusion device.

PMID- 16954595
TI  - Neurovascular coupling and oximetry during epileptic events.
AB  - Epilepsy is an abnormal brain state in which a large population of neurons is
      synchronously active, causing an enormous increase in metabolic demand. Recent
      investigations using highresolution imaging techniques, such as optical recording
      of intrinsic signals and voltagesensitive dyes, as well as measurements with
      oxygen-sensitive electrodes have elucidated the spatiotemporal relationship
      between neuronal activity, cerebral blood volume, and oximetry in vivo. A focal
      decrease in tissue oxygenation and a focal increase in deoxygenated hemoglobin
      occurs following both interictal and ictal events. This "epileptic dip" in
      oxygenation can persist for the duration of an ictal event, suggesting that
      cerebral blood flow is inadequate to meet metabolic demand. A rapid focal
      increase in cerebral blood flow and cerebral blood volume also accompanies
      epileptic events; however, this increase in perfusion soon (>2 s) spreads to a
      larger area of the cortex than the excitatory change in membrane potential.
      Investigations in humans during neurosurgical operations have confirmed the
      laboratory data derived from animal studies. These data not only have clinical
      implications for the interpretation of noninvasive imaging studies such as
      positron emission tomography, single-photon emission tomography, and functional
      magnetic resonance imaging but also provide a mechanism for the cognitive decline
      in patients with chronic epilepsy.

PMID- 16954596
TI  - Changes in the expression of G protein-coupled receptor kinases and beta
      arrestins in mouse brain during cannabinoid tolerance: a role for RAS-ERK
      cascade.
AB  - The focus of our study was to determine the role of G protein-coupled receptor
      kinases (GRKs) and beta-arrestins in agonist-induced CB1 receptor modulation
      during cannabinoid tolerance and their dependence from the extracellular signal
      regulated kinase (ERK) cascade. In wild-type mice, chronic Delta9
      tetrahydrocannabinol (THC) exposure significantly activated specific GRK and beta
      arrestin subunits in all the considered brain areas (striatum, cerebellum,
      hippocampus, and prefrontal cortex), suggesting their involvement in the adaptive
      processes underlying CB1 receptor downregulation and desensitization. These
      events were ERK-dependent in the striatum and cerebellum, because they were
      prevented in the genetic (Ras-GRF1 knockout mice) and pharmacological (SL327
      pretreated mice) models of ERK activation inhibition, whereas in the hippocampus
      and prefrontal cortex, they appeared to be mostly ERK-independent. In the latter
      areas, ERK activation after chronic THC increased the transcription factors
      cyclic adenosine monophosphate response element-binding protein and Fos B as well
      as a downstream protein known as brainderived neurotrophic factor. As a whole,
      our data suggest that in the striatum and cerebellum, THC-induced ERK activation
      could represent a key signaling event to initiate homologous desensitization of
      CB1 receptor, accounting for the development of tolerance to THC-induced
      hypolocomotion. In the prefrontal cortex and hippocampus, THC-induced alteration
      in GRKs and beta-arrestins primarily depends on other kinases, whereas ERK
      activation could be part of the molecular adaptations that underlie the complex
      behavioral phenotype that defines the addicted state.

PMID- 16954597
TI  - Calpain and synaptic function.
AB  - Proteolysis by calpain is a unique posttranslational modification that can change
      integrity, localization, and activity of endogenous proteins. Two ubiquitous
      calpains, mu-calpain and m-calpain, are highly expressed in the central nervous
      system, and calpain substrates such as membrane receptors, postsynaptic density
      proteins, kinases, and phosphatases are localized to the synaptic compartments of
      neurons. By selective cleavage of synaptically localized molecules, calpains may
      play pivotal roles in the regulation of synaptic processes not only in
      physiological states but also during various pathological conditions. Activation
      of calpains during sustained synaptic activity is crucial for Ca2+-dependent
      neuronal functions, such as neurotransmitter release, synaptic plasticity,
      vesicular trafficking, and structural stabilization. Overactivation of calpain
      following dysregulation of Ca2+ homeostasis can lead to neuronal damage in
      response to events such as epilepsy, stroke, and brain trauma. Calpain may also
      provide a neuroprotective effect from axotomy and some forms of glutamate
      receptor overactivation. This article focuses on recent findings on the role of
      calpain-mediated proteolytic processes in potentially regulating synaptic
      substrates in physiological and pathophysiological events in the nervous system.

PMID- 16954598
TI  - N-cadherin signaling in synapse formation and neuronal physiology.
AB  - Neural cadherin (N-cadherin) is an adhesion receptor that is localized in
      abundance at neuronto- neuron synapses. N-cadherin contains an extracellular
      domain that binds to other cadherins on juxtaposed cell membranes, a single-pass
      transmembrane region, and a cytoplasmic tail that interacts with various
      proteins, including catenins, kinases, phosphatases, and presenilin 1. N-cadherin
      contributes to the structural and functional organization of the synaptic complex
      by ensuring the adhesion between synaptic membranes and organizing the underlying
      actin cytoskeleton. Additionally, recent findings have shown that N-cadherin may
      participate in synaptic physiology by regulating calcium influx through voltage
      activated calcium currents. The diverse activities of N-cadherin stem from its
      ability to operate as both an adhesion molecule that links cytoskeletons across
      cell membranes and a ligand-activated homophilic receptor capable of initiating
      intracellular signaling. An important mechanism of cadherin signaling is the
      regulation of small Rho guanosine triphosphatase activity that affects
      cytoskeleton dynamics and calcium influx. Because both the regulation of cadherin
      adhesive activity and cadherin-mediated signaling are affected by the binding of
      molecules to the intracellular domain, changes in the composition of the N
      cadherin complex are central to the regulation of cadherin-mediated functions.
      This article focuses on the roles that N-cadherin might play at the level of the
      synapse through its effect on adhesion and signaling in the proximity of the
      synaptic junction.

PMID- 16954600
TI  - Distribution of NPY Y5-like immunoreactivity in the rat brain.
AB  - The pharmacology and brain mRNA distribution of the neuropeptide Y (NPY) rat Y5
      (rY5) receptor has led to the hypothesis that this receptor might mediate the
      hypothalamic feeding response to NPY in addition to many other physiologic
      functions. However, through the use of autoradiographic techniques, only very low
      levels of Y5-like immunoreactive (Y5-ir) binding are detected in the rat brain.
      To localize the Y5 protein in the rat brain, polyclonal antibodies were raised to
      the carboxyl terminus of the rY5 receptor. The resulting antisera were affinity
      purified and characterized by specific binding to HEK293 cells that had been
      stably transfected with the rY5 receptor. Utilizing immunohistochemical
      techniques, we found a discrete pattern of Y5-ir in the rat brain. In initial
      studies, very low levels of Y5-ir were detected, and TSA amplification was
      required to visualize the staining. Areas with the highest levels of expression
      include the piriform cortex, supraoptic nucleus, and hippocampus. Areas with
      moderate levels of expression include the lateral septum, amygdala, arcuate
      nucleus, paraventricular hypothalamic nucleus, locus coeruleus, and cerebellum.
      With several exceptions, this pattern of distribution is consistent with earlier
      reports of rY5 mRNA and receptor protein expression.

PMID- 16954599
TI  - Pharmacological characterization of orally active cholinesterase inhibitory
      activity of Prunus persica L. Batsch in rats.
AB  - Prunus persica L. Batsch water extract (PPE) is a potent acetylcholinesterase
      (AChE) inhibitor screened for the treatment of Alzheimer's disease. The effects
      of oral administration of the PPE were examined with comparison of those of
      selective butyrylcholinesterase inhibitors of 9-amino-1,2,3,4-tetrahydroacridine
      hydrochloride (tacrine) and tetraidopropylpyrophosphoramide (iso-OMPA) and a
      selective AChE inhibitor, donepezil, on the cholinesterase activity in the brain
      and plasma of rats. After the sequential solvent fractionation of the methanol
      extract of P. persica L. Batsch, the highest inhibitory fraction was that of
      chloroform (75%). The concentration that was required for 50% enzyme inhibition
      (IC(50) value) was 5.6 microg/mL for the chloroform fraction. Oral administration
      of PPE or tacrine caused a dose-dependent inhibition of brain and plasma
      cholinesterase activities. The ID(50) values of these compounds for brain
      cholinesterase activity were 2.7 g/kg and 8.9 mg/kg, respectively. On the other
      hand, the ID(50) values for plasma cholinesterase activity were 18.6 g/kg and
      27.5 mg/kg, respectively. Thus, the ratios of the ID(50) (plasma < brain) were
      6.0 and 3.1, respectively. These results suggest that orally administered PPE
      satisfactorily penetrates into the brain and inhibits cholinesterase there and
      that PPE is a potent inhibitor of brain cholinesterase in comparison with plasma
      cholinesterase in vivo.

PMID- 16954601
TI  - Inhibition of AC-II activity following chronic agonist exposure is modulated by
      phosphorylation.
AB  - Chronic exposure to opiate agonists (followed by agonist withdrawal) leads to a
      large increase in the activity of adenylyl cyclase (AC) isozymes I, V, VI, and
      VIII, a phenomenon defined as AC superactivation (or supersensitization). On the
      other hand, AC isozymes belonging to the AC-II family (AC-II, AC-IV, and AC-VII)
      show decreased activity, referred to as superinhibition. Using COS-7 cells
      transiently transfected with mu-opioid receptor and AC-II, we show here that
      inhibition of PKC and tyrosine kinase activities synergistically reduced the
      level of AC-II superinhibition. Moreover, inhibitor of Raf-1 kinase also led to a
      decrease in AC-II superinhibition. These data suggest that Raf-1, activated by
      PKC and tyrosine kinase, has a role in the regulation of AC-II superinhibition.

PMID- 16954602
TI  - Tpc1808 increases expression of NF-H in PC12 cells.
AB  - Tpc1808 is a candidate chemotropic factor induced by nerve injury, and we report
      here the role of rat Tpc1808 in the expression of high-molecular-weight
      neurofilament (NF-H) in PC12 cells. A full-length Tpc1808 cDNA encoding the 275
      amino-acid protein was constructed into pcDNA-HA and transfected into PC12 cells.
      The increased expression of NF-H was detectable in PC12-Tpc1808 clones by semi
      qRT-PCR, real-time PCR, Western blot, and immunofluorescence. Such an increase
      could also be observed in PC12 cells subjected to recombinant Tpc1808 protein by
      real-time PCR and immunohistochemistry. At a concentration of 0.1 microg/mL,
      Tpc1808 protein, similar to NGF, could promote the expression of NF-H in a time
      dependent manner. Our findings suggest that Tpc1808 is the gene related to
      promotion of nerve growth, and both the Tpc1808 gene and the Tpc1808 recombinant
      protein up-regulate the expression of NF-H in PC12 cells.

PMID- 16954603
TI  - Lack of association of HIV-1 biological or molecular properties with neurotropism
      for brain cells.
AB  - Despite HAART, a significant number of HIV-1-infected patients develop
      neurological complications. However, the presence of specific neurotropic HIV-1
      strains, the extent of viral replication in the brain, and the type of cells
      infected remain controversial issues. To address this controversy we have
      analyzed different V3 loop sequences of viral isolates from four vertically HIV-1
      infected children who developed HIV-1-related encephalopathy. Moreover, we have
      determined that some biological and molecular properties of HIV-1 might
      contribute to AIDS neurological dysfunctions. We detected very different HIV-1
      isolates (X4 and R5) in the brain despite no great differences in clinical,
      pathological, or immunological parameters. In vitro, no differences in
      replicative competence in glial or neuroblastoma cells were observed between
      virus isolated from the blood of children with or without clinical neurological
      symptoms. The expression of both CXCR4 and CCR5 RNAs was observed in the brain
      independently of HIV-1 infection and viral strain predominant in this location.
      Our results failed to show a particular phenotypic property of the HIV-1 virus
      that might explain its neurovirulence and/or neurotropism.

PMID- 16954604
TI  - Gangliocytes in neuroblastic tumors express alarin, a novel peptide derived by
      differential splicing of the galanin-like peptide gene.
AB  - In neuroblastic tumors a relationship of differentiation of the tumor to galanin
      receptor expression and antiproliferative and apoptotic effects upon activation
      of galanin receptors in neuroblastoma cells was reported. To elucidate the
      expression of other components of the galanin peptide family in neuroblastic
      tumors, RT-PCR analysis of a variety of human neuroblastic tumor tissues was
      performed. Ganglioneuroma tissues revealed the presence of a splice variant of
      the galanin-like peptide (GALP) mRNA, which results in exclusion of exon 3 and a
      frame shift after the signal peptide sequence of GALP. This generates a peptide
      of 25 amino acids, which we have termed alarin because of the N-terminal alanine
      and the C-terminal serine. The novel neuropeptide alarin does not reveal
      significant homology to other peptides. Immunohistochemistry with antibodies
      directed against synthetic alarin peptide detected specific cytoplasmic granular
      staining in ganglia of human ganglioneuroma and ganglioneuroblastoma, as well as
      differentiated tumor cells of neuroblastoma tissues. Undifferentiated neuroblasts
      of these tumor tissues did not show alarin-like immunoreactivity and alarin
      specific mRNA. Our findings indicate that alarin expression is a feature of
      ganglionic differentiation in neuroblastic tumor tissues.

PMID- 16954605
TI  - The dynamic instability of microtubules is required for aggresome formation in
      oligodendroglial cells after proteolytic stress.
AB  - University of Oldenburg, Department of Biology, Molecular Neurobiology, D-26111
      Oldenburg, Germany Ubiquitinated tau-positive inclusion bodies in
      oligodendrocytes are consistent features in a variety of neurodegenerative
      disorders, and their formation points to an underlying incapacity of the protein
      quality control system that normally prevents the accumulation of misfolded
      proteins. To study the consequences of proteasomal impairment, we have used an
      oligodendroglial cell line, namely OLN-t40 cells, genetically engineered to
      express the longest human tau isoform. Treatment of OLN-t40 cells with the
      proteasomal inhibitor MG-132 (0.5 microM, 18 h) caused the formation of large,
      nonfibrillary tau-positive aggregates containing the small HSP alphaB-crystallin
      and ubiquitin in the vicinity of the microtubule organizing center (MTOC). The
      sequestration of misfolded proteins into specialized regions, called aggresomes,
      in response to stress stimuli has been reported to be associated with a
      redistribution of intermediate filaments (IFs). In oligodendroglial cells, which
      do not contain a cytoplasmic IF system, aggresomelike inclusions were instead
      surrounded by bundles of MTs and contained clusters of mitochondria. Aggresome
      formation was prevented by both MT-stabilizing and -destabilizing drugs,
      indicating not only that an intact cytoskeleton but also the dynamic instability
      of the MT network is required. Furthermore, the binding of stress-induced
      alphaBcrystallin to the MTs points to a possible protective role during disease
      progression.

PMID- 16954606
TI  - Dopamine-1 receptor agonist, but not cocaine, modulates sigma(1) gene expression
      in SVG cells.
AB  - It has been hypothesized that sigma(1) receptors (sigma(1)Rs) are involved in the
      effects of cocaine abuse. Many in vitro and in vivo studies have already
      indicated an influence of sigma(1)R ligands on dopaminergic transmission;
      however, the direct effect on the brain is poorly understood. Herein we describe
      the effects of cocaine and the selective dopamine-1 receptor (D(1)R) agonist, (+)
      SKF38393, on gene expression of the sigma(1)R in a human fetal astrocyte cell
      line (SVG cells). This study provides the first evidence for the expression of
      sigma(1)RmRNAin these cells. Our results show that treatment of SVG cells with
      various cocaine concentrations for several time durations showed no significant
      alterations in sigma(1)R gene expression, as detected by real-time quantitative
      RT-PCR, whereas treating cells for 24 h with (+)-SKF38393 caused a significant
      down-regulation in sigma(1) transcripts. This (+)-SKF38393-induced effect was
      blocked by the D(1)R selective antagonist (+)-SCH23390. These results suggest
      that the effect of cocaine on sigma(1) gene expression in the brain might be
      indirect and mediated through D(1)R.

PMID- 16954608
TI  - Meta-barium borate, II-BaB2O4, at 163 and 293 K.
AB  - The single-crystal X-ray diffraction structure analysis of an excellent non
      linear optical material, viz. II-BaB2O4 or Ba3(B3O6)2, has been carried out at
      163 and 293 K. The two sets of structural data are compared and indicate a
      significant shortening of the c axial length in the unit cell at 163 K, whereas
      the a and b axial lengths essentially do not change.

PMID- 16954607
TI  - Apolipoprotein A5 gene promoter region T-1131C polymorphism associates with
      elevated circulating triglyceride levels and confers susceptibility for
      development of ischemic stroke.
AB  - The possible pathogenic role of triglycerides (TG) in the development of ischemic
      stroke is still under extensive investigation. Recently, apolipoprotein (apo)A5
      gene promoter region T-1131C polymorphism has been shown to associate with
      elevated serum TG levels. In the current work, a total of 302 subjects were
      classified as being large vessel-associated, small vessel-associated, or
      belonging to a mixed group of ischemic stroke-affected patients. The level of TG
      was increased in all groups (p < 0.01). The apoA5-1131C allele frequency was
      approximately twofold in all groups of stroke patients compared with the controls
      (5 vs 10-12%; p < 0.05); and the apoA5-1131C allele itself was also found to
      associate with increased TG levels in all groups. In a multivariate logistic
      regression analysis model adjusted for differences in age, gender, serum
      cholesterol, hypertension, presence of diabetes mellitus, smoking and drinking
      habits, and ischemic heart disease, a significantly increased risk of developing
      stroke disease was found in patients carrying the apoA5-1131C allele (p < 0.05;
      odds ratio OR = 2.1 [1.3-4.7]); this association was also proven for all subtypes
      of the stroke. The results presented here suggest that the apoA5-1131C allele is
      an independent risk factor for the development of stroke. Being that apoA5 gene
      is under the control of the peroxisome proliferator-activated receptor alpha,
      theoretically, the current observations also can have long-term therapeutic
      consequences.

PMID- 16954609
TI  - Lithium dioxobis[trioxoiodato(V)]vanadate, Li[VO2(IO3)2].
AB  - The title compound represents a new structure type, in which distorted VO6
      octahedra are bridged by iodate groups to form infinite two-dimensional
      [VO2(IO3)2]- layers that are separated by octahedrally coordinated Li+ cations.

PMID- 16954610
TI  - Triaquamanganese sulfite revisited.
AB  - Orthorhombic Mn(SO3)(H2O)3 has been reinvestigated by single-crystal X-ray
      diffraction in two possible space groups, viz. P2(1)2(1)2(1) (with all atoms in
      general positions) and Pnma (with the molecule bisected by a mirror plane). The
      results confirm the lower symmetry assigned in a previous single-crystal neutron
      diffraction study. However, the refinement of the P2(1)2(1)2(1) model requires
      the introduction of racemic twinning and soft positional and displacement
      restraints for the H atoms. The importance of a scrupulous report on symmetry
      absence violations as standard policy in crystallographic work is discussed.

PMID- 16954611
TI  - Gamma-alumina: a single-crystal X-ray diffraction study.
AB  - The structure of gamma-alumina (Al21+1/3square2+2/3O32) crystals obtained as a
      product of a corrosion reaction between beta-sialon and steel was refined in the
      space group Fd3m. The oxygen sublattice is fully occupied. The refined occupancy
      parameters are 0.83 (3), 0.818 (13), 0.066 (14) and 0.044 (18) for Al ions in 8a,
      16d, 16c and 48f positions, respectively. The Al ions are distributed over
      octahedral and tetrahedral sites in a 63:37 ratio, with 6% of all Al ions
      occupying non-spinel positions.

PMID- 16954612
TI  - Tetrakis[2-(2-pyridyl)pyridinium] tetra-mu3-iodo-hexa-mu2-iodo
      dodecaiodohexabismuthate and bis[tris(2,2'-bipyridine)ruthenium(II)] di-mu4-iodo
      octa-mu2-iodo-dodecaiodohexabismuthate.
AB  - Crystals of the title compounds were grown solvothermally in an ethanol-water
      solvent mixture using ruthenium triiodide, 2,2'-bipyridine and bismuth triiodide
      as starting materials. Tetrakis[2-(2-pyridyl)pyridinium] tetra-mu3-iodo-hexa-mu2
      iodo-dodecaiodohexabismuthate, (C10H9N2)4[Bi6I22], crystallizes in the triclinic
      space group P-1 and is the major reaction product. The asymmetric unit of this
      compound consists of half a centrosymmetric [Bi6I22]4- anion and two independent
      2,2'-bipyridinium cations. The minor product of the reaction is bis[tris(2,2'
      bipyridine)ruthenium(II)] di-mu4-iodo-octa-mu2-iodo-dodecaiodohexabismuthate,
      [Ru(C10H8N2)3]2[Bi6I22], which also crystallizes in the triclinic space group P
      1. For this compound, the asymmetric unit consists of one full [Ru(2,2'
      bipyridine)3]2+ cation and half a centrosymmetric [Bi6I22]4- anion. Although both
      compounds contain a centrosymmetric [Bi6I22]4- anion, the polyhedral arrangement
      of the distorted BiI6 octahedra in the two compounds is quite different, and the
      anion of the latter compound has not previously been observed in iodobismuthate
      chemistry.

PMID- 16954613
TI  - {2,5-Bis[3-(tert-butylaminoxyl)phenyl]-1,1-dimethyl-3,4-diphenylsilole
      kappaO}bis(1,1,1,5,5,5-hexafluoropentane-2,4-dionato)manganese(II).
AB  - In the structure of the first bis-adduct of 2,5-bis[3-(tert-butylaminoxyl)phenyl]
      1,1-dimethyl-3,4-diphenylsilole with bis(hexafluoroacetylacetonato)manganese(II),
      [Mn(C5HF6O2)2(C38H42N2O2Si)2], the Mn atom lies on a crystallographic inversion
      centre and is bound to two chelating hexafluoroacetylacetonate ligands and two
      monodentate nitroxide groups in a distorted octahedral configuration. The silole
      ligands present a propeller-like arrangement of the benzene rings around the Si
      containing five-membered ring. The dihedral angles between the complexed
      nitroxides and the benzene rings to which they are bound are smaller than those
      found in the free ligand.

PMID- 16954614
TI  - Poly[[diaquacadmium(II)]-mu4-[N-(phosphonatomethyl)ammonio]acetato].
AB  - The title compound, [Cd(C3H6NO5P)(H2O)2]n, is a three-dimensional polymeric
      complex. The asymmetric unit contains one Cd atom, one N-(phosphonomethyl)glycine
      zwitterion [(O-)2OPCH2NH2+CH2COO-] and two water molecules. The coordination
      geometry is a distorted CdO6 octahedron. Each N-(phosphonomethyl)glycine ligand
      bridges four adjacent water-coordinated Cd cations through three phosphonate O
      atoms and one carboxylate O atom, like a regular PO(4)3- group in zeolite-type
      frameworks. One-dimensional zigzag (-O-P-C-N-C-C-O-Cd-)n chains along the [101]
      direction are linked to one another via Cd-O-P bridges and form a three
      dimensional network motif with three types of channel systems. The variety of O
      H...O and N-H...O hydrogen bonds is likely to be responsible for stabilizing the
      three-dimensional network structure and preventing guest molecules from entering
      into the channels.

PMID- 16954615
TI  - Catena-poly[[aqua(2,2'-bipyridine-kappa2N,N')cadmium(II)]-mu-4
      carboxylatophenoxyacetato-kappa3O:O4,O4'].
AB  - In the title compound, [Cd(C9H6O5)(C10H8N2)(H2O)]n, the CdII atom is coordinated
      in a distorted octahedral fashion by two carboxylate groups (one in a monodentate
      and one in a bidentate fashion) from two 4-carboxylatophenoxyacetate anions, two
      N atoms from a 2,2'-bipyridine ligand and one aqua ligand. The structure is a
      helix with a long pitch of 16.441 (5) A. A three-dimensional supramolecular
      network is further constructed through pi-pi stacking and hydrogen-bonding
      interactions between the helices.

PMID- 16954616
TI  - Poly[aqua(mu3-benzene-1,2-dicarboxylato)(mu2-hydroxo)indium(III)].
AB  - In the title compound, [In(C8H4O4)(OH)(H2O)]n, the coordination of the InIII ion
      is composed of six O atoms from three dianionic benzene-1,2-dicarboxylate
      ligands, two hydroxyl groups and one coordinated water molecule in a distorted
      octahedral geometry. The In3+ ions are linked by the hydroxyl groups to form
      zigzag In-OH-In chains, which are further bridged by the benzene-1,2-dicarboxylic
      acid ligands to generate a two-dimensional layered structure featuring three
      types of rings (six-, 14- and 20-membered). Hydrogen bonds between the water
      molecule and a carboxylate O atom, and between the hydroxyl group and a
      carboxylate O atom, are observed within the layers. In the crystal packing, there
      are pi-pi stacking interactions between the benzene rings of adjacent layers,
      with a centroid-to-centroid distance of 3.668 (3) A and a dihedral angle of 4.8
      (2) degrees.

PMID- 16954617
TI  - Dichloro[(1E,1'E)-1,1'-(pyridine-2,6-diyl)diethanone bis(O-methyloxime)
      kappa3N1,N2,N6]cobalt(II).
AB  - In the title compound, [CoCl2(C11H15N3O2)], the CoII ion is five-coordinated in a
      strongly distorted square-pyramidal arrangement, with one of the two Cl atoms
      located in the apical position, and the other Cl atom and the three N-donor atoms
      of the tridentate methyloxime ligand located in the basal plane. The non-H atoms,
      except for the Cl atoms, lie on a mirror plane. The two equatorial Co-Noxime
      distances are almost equal (mean 2.253 A) and are substantially longer than the
      equatorial Co-Npyridine bond [2.0390 (19) A]. The structure is stabilized by
      intra- and intermolecular C-H...Cl contacts, which involve one of the methyl C
      atoms belonging to the methyloxime groups.

PMID- 16954618
TI  - Bis(acesulfamato-kappa2O4,N)bis(3-methylpyridine)copper(II).
AB  - In the crystal structure of the title compound {systematic name: bis[6-methyl
      1,2,3-oxathiazin-4(3H)-one 2,2-dioxide(1-)-kappa2N3,O4]bis(3
      methylpyridine)copper(II)}, [Cu(C4H4NO4S)2(C6H7N)2], the CuII centre resides on a
      centre of symmetry and has an octahedral geometry that is distorted both by the
      presence of four-membered chelate rings and because of the Jahn-Teller effect.
      The equatorial plane is formed by the N atoms of two methylpyridine ligands and
      by the more basic O atoms of the acesulfamate ligands, while the weakly basic N
      atoms of these ligands are in elongated axial positions with a misdirected
      valence. The crystal is stabilized by two intermolecular C-H...O interactions
      involving the methyl and CH groups, and the sulfonyl O atoms of the acesulfamate
      group.

PMID- 16954619
TI  - An unusual eight-coordinated copper complex: bis(4,7-diphenyl-1,10
      phenanthroline)dinitratocopper(II).
AB  - In the title monomer, [Cu(NO3)2(C24H16N2)2], the copper(II) cation is eight
      coordinate within an octahedral-like polyhedron. The coordination polyhedron is
      formed by two chelating diphenylphenanthroline groups that define the highly
      distorted CuN4 equatorial plane and two weakly bound bidentate (chelating)
      nitrate groups in the apical or axial positions. The complex crystallizes in the
      monoclinic space group C2/c; a twofold axis passes through the copper(II) cation
      and bisects the two nitrate ligands. This gives the molecule C2 point-group
      symmetry, rendering only half of the molecule independent.

PMID- 16954620
TI  - (Z)-1-Ferrocenyl-3-(3-hydroxyanilino)but-2-en-1-one and (Z)-1-ferrocenyl-3-(4
      hydroxyanilino)but-2-en-1-one.
AB  - The title compounds, both [Fe(C5H5)(C15H14NO2)], crystallize with Z'=2 in the
      centrosymmetric space group P-1. In each compound, there is an intramolecular N
      H...O=C hydrogen bond, and pairs of intermolecular O-H...O=C hydrogen bonds link
      the molecules into chains, parallel to [110] in the 3-hydroxy compound and
      parallel to [101] in the 4-hydroxy compound.

PMID- 16954621
TI  - Catena-poly[[(trifluoromethanesulfonato-kappaO)silver(I)]-mu-di-2-pyridylamine
      kappa2N2:N2'], a chain polymer with short Ag...C contacts.
AB  - The title compound, [Ag(CF3O3S)(C10H9N3)]n, is a chain polymer in which
      neighbouring monomeric units are related by a glide plane. The silver centre is
      four-coordinate; the donor atoms are one trifluoromethanesulfonate O atom and one
      pyridine N atom from each of two symmetry-related dipyridylamines, and an
      additional and unexpected Ag...C contact [2.6464 (16) A] is observed to a
      pyridine C atom. The chains are reinforced by one classical N-H...O and two
      'weak' C-H...O hydrogen bonds.

PMID- 16954622
TI  - Poly[propane-1,3-diyldiammonium tetra-mu-selenito-trizinc dihydrate].
AB  - The title compound, (C3H12N2)[Zn3(SeO3)4].2H2O, is built up from organic cations,
      {[Zn3(SeO3)4]2-}n macroanionic sheets and water molecules. The inorganic
      component of the structure is notable for incorporating both octahedrally and
      tetrahedrally coordinated Zn atoms. A network of N-H...O and O-H...O hydrogen
      bonds helps to establish the layered structure. The six-coordinate Zn atom has
      site symmetry 1, and one C and the two water O atoms have site symmetry m.

PMID- 16954623
TI  - Supramolecular structure and second harmonic generation in strontium bis(hydrogen
      L-malate) hexahydrate.
AB  - The title compound, tetraaquabis(hydrogen L-malato)strontium(II) dihydrate,
      [Sr(C4H5O5)2(H2O)4].2H2O, is a new non-linear optical semi-organic material with
      a second harmonic generation efficiency approximately 3.5 times greater than that
      of potassium dihydrogen phosphate. The malate anions are interconnected through
      directional O-H...O hydrogen bonding, in a head-to-tail arrangement, creating
      extended anionic chains along [001]. Neighbouring parallel chains are crosslinked
      by water molecules, resulting in a three-dimensional architecture. The Sr2+ ion
      is coordinated by eight O atoms. This material is a new candidate for non-linear
      optical applications since the crystals are stable and easy to grow.

PMID- 16954624
TI  - Sodium trichloromethanesulfonate monohydrate.
AB  - Sodium trichloromethanesulfonate monohydrate, Na+.CCl3SO3-.H2O, crystallizes in
      P2(1)/a with all the atoms located in general positions. The
      trichloromethanesulfonate (trichlate) anion consists of pyramidal SO3 and CCl3
      groups connected via an S-C bond in a staggered conformation with approximate C3v
      symmetry. The water molecule is hydrogen bonded to the sulfonate O atoms, with
      one water H atom forming weak bifurcated O-H...O hydrogen bonds to two different
      trichlate ions. Two water O atoms and three O atoms from different SO3 groups
      form a square-pyramidal arrangement around the sodium ion.

PMID- 16954625
TI  - Trans-bis[3,5-bis(trifluoromethyl)-1H-pyrazole-kappaN2]dichloropalladium(II)
      monohydrate.
AB  - The palladium(II) center in the title compound, trans-[PdCl2(C5H2F6N2)2].H2O,
      possesses a distorted square-planar geometry. The NH groups are positioned on the
      same side of the PdN2Cl2 coordination plane. Four symmetry-independent strong
      hydrogen bonds of three types (N-H...Cl, N-H...Cl and O-H...Cl) hold the
      structure together.

PMID- 16954626
TI  - Partially oxidized ruthenium phosphine thiolates: [Ru(pySO2)0.33(pyS)1.67(dppe)]
      and [Ru(pySO2)0.355(pyS)1.645(dppp)].
AB  - The crystal structures of [1,3-bis(diphenylphosphino)ethane-kappa2P,P'](pyridine
      2-sulfinato-kappa2N,S)(pyridine-2-thiolato-kappa2N,S)ruthenium(II),
      [Ru(C5H4NO2S)0.33(C5H4NS)1.67(C26H24P2)] or [Ru(pySO2)1-x(pyS)1+x(dppe)]
      (x=0.67), (I), and [1,3-bis(diphenylphosphino)propane-kappa2P,P'](pyridine-2
      sulfinato-kappa2N,S)(pyridine-2-thiolato-kappa2N,S)ruthenium(II),
      [Ru(C5H4NO2S)0.355(C5H4NS)1.645(C27H26P2)] or [Ru(pySO2)1-x(pyS)1+x(dppp)]
      (x=0.645), (II), are composed of neutral distorted octahedral RuII complexes with
      chelating pyridine-2-thiolate, pyridine-2-sulfinate and biphosphine ligands. The
      S atoms are trans to each other, while pairs of P and N atoms are in cis
      positions. Partial double-bond character is observed for C-S. The crystal packing
      consists of monolayers stabilized by C-H...O and C-H...S interactions, and is
      affected by the alkyl-chain lengths.

PMID- 16954627
TI  - A one-dimensional mixed-anion lead(II) coordination polymer: catena-poly[[(1,10
      phenanthroline)lead(II)]-mu-benzoato-mu-nitrato-[(1,10-phenanthroline)lead(II)]
      di-mu-benzoato].
AB  - In the title polymeric compound, [Pb2(C7H5O2)3(NO3)(C12H8N2)2]n, both independent
      Pb atoms adopt an eight-coordinate geometry formed by one nitrate, three benzoate
      and one 1,10-phenanthroline ligand. The one-dimensional polymer consists of
      dimeric [Pb2(C7H5O2)3(NO3)(C12H8N2)2] units, in which all nitrate and benzoate
      ligands act in a bridging-chelating coordination mode.

PMID- 16954628
TI  - Poly[tetra-mu-aqua-hexaaquadi-mu3-malonato-dinitratodibarium(II)nickel(II)].
AB  - The title complex, [Ba2Ni(C3H2O4)2(NO3)2(H2O)10]n, has a two-dimensional layer
      structure. The Ni atom lies on a crystallographic centre of symmetry in an
      octahedral NiO6 environment, and is coordinated by four malonate O atoms in a
      planar arrangement and by two water molecules in axial positions. The
      coordination of the unique Ba atom involves two nitrate O atoms, five water
      molecules and three malonate O atoms.

PMID- 16954629
TI  - Diaquabis(ethylenediamine)cadmium(II) bis(4-aminonaphthalene-1-sulfonate)
      dihydrate.
AB  - In the title compound, [Cd(C2H8N2)2(H2O)2](C10H8NO3S)2.2H2O, the CdII atom,
      located on an inversion centre, has a distorted octahedral coordination geometry
      formed by two ethylenediamine and two water molecules. 4-aminonaphthalene-1
      sulfonate acts as a counter-ion to balance the charge, and two antiparallel
      anions showing strong pi-pi stacking interactions are linked by paired N
      H...O(sulfonate) hydrogen bonds into an isolated R2(2)(16) dimer. The crystal
      structure is stabilized by the pi-pi stacking interactions and hydrogen bonds.

PMID- 16954630
TI  - An unusual example of a linearly coordinated acetone ligand in a six-coordinate
      iron(II) complex.
AB  - The title compound, acetonediaqua[2,6-bis(3-tert-butylpyrazol-1
      yl)pyridine]iron(II) bis(tetrafluoroborate) acetone disolvate,
      [Fe(C19H25N5)(C3H6O)(H2O)2](BF4)(2).2C3H6O, contains a C2-symmetric six
      coordinate complex dication, with an acetone ligand in its equatorial plane that
      is linearly coordinated by symmetry (Fe-O=CMe2=180 degrees). This is a
      consequence of close steric contacts between the coordinated carbonyl group and
      the two distal tert-butyl substituents on the tridentate ligand.

PMID- 16954631
TI  - A novel 8-carboxyindeno[1,2-b]quinoxalin-11-one thiosemicarbazone zinc(II) Schiff
      base complex.
AB  - In the novel title binuclear zinc(II) Schiff base complex, bis(mu-11
      thiosemicarbazonoindeno[1,2-b]quinoxaline-8-carboxylato)bis[(dimethyl
      sulfoxide)zinc(II)] dimethyl sulfoxide trisolvate,
      [Zn2(C17H9N5O2S)2(C2H6OS)2].3C2H6OS, each ZnII atom is five-coordinated and
      situated in a distorted square-pyramidal environment, coordinated by two L2-
      ligands and one dimethyl sulfoxide molecule. Each L2- ligand, which coordinates
      to two ZnII atoms, has two parts. One part, acting in a tridentate chelating
      mode, coordinates to one ZnII atom through two N atoms and one S atom, while
      another part coordinates to another ZnII atom through a monodentate carboxylate
      group. The whole complex has a dimeric structure. The coordination mode of the
      nearly planar L2- ligand is quite different from the most common mode for Schiff
      bases.

PMID- 16954632
TI  - Two-dimensional square-grid frameworks formed by self-associating copper(II)
      complexes with 1-(3-pyridyl)- and 1-(4-pyridyl)-substituted butane-1,3-diones.
AB  - In bis[1-(3-pyridyl)butane-1,3-dionato]copper(II) (the Cu atom occupies a centre
      of inversion), [Cu(C9H8NO2)2], (I), and bis[1-(4-pyridyl)butane-1,3
      dionato]copper(II) methanol solvate, [Cu(C9H8NO2)2].CH3OH, (II), the O,O'
      chelating diketonate ligands support square-planar coordination of the metal ions
      [Cu-O=1.948 (1)-1.965 (1) A]. Weaker Cu...N interactions [2.405 (2)-2.499 (2) A],
      at both axial sides, occur between symmetry-related bis(1-pyridylbutane-1,3
      dionato)copper(II) molecules. This causes their self-organization into two
      dimensional square-grid frameworks, with uniform [6.48 A for (I)] or alternating
      [4.72 and 6.66 A for (II)] interlayer separations. Guest methanol molecules in
      (II) reside between the distal layers and form weak hydrogen bonds to coordinated
      O atoms [O...O=3.018 (4) A].

PMID- 16954633
TI  - catena-Poly[[[triaquasulfatocobalt(II)]-mu-4,4'-bipyridine] ethane-1,2-diol
      solvate].
AB  - In the title compound, {[Co(SO4)(C10H8N2)(H2O)3].C2H6O2}n, each CoII center is
      octahedrally coordinated by two N atoms from two bridging 4,4'-bipyridine (bipy)
      ligands and four O atoms, one from a monodentate sulfate ligand and three from
      aqua ligands. The bipy ligands occupy special positions of site symmetry -1 and
      bridge adjacent cobalt(II) centers to form one-dimensional linear coordination
      chains. Adjacent chains are arranged in a cross-like fashion around the mid-point
      of the bipy ligands, resulting in a three-dimensional supramolecular array.

PMID- 16954634
TI  - Paddlewheel dirhodium complexes bridged by para-substituted benzoates.
AB  - The dirhodium complex bis(benzonitrile)tetrakis[mu-4-(diethylamino)benzoato
      kappa2O:O']dirhodium(II)(Rh-Rh) benzonitrile disolvate,
      [Rh2(C11H14NO2)4(C7H5N)2].2C7H5N, lies about an inversion centre. The dirhodium
      complex (methanol)tetrakis(mu-4-nitrobenzoato
      kappa2O:O')(pyridine)dirhodium(II)(Rh-Rh) dichloromethane solvate,
      [Rh2(C7H4NO4)4(C5H5N)(CH4O)].CH2Cl2, lies in a general position in the unit cell,
      but the complexes dimerize around an inversion centre via O-H...O hydrogen
      bonding of the axial MeOH to a carboxylate O atom. In the latter crystal
      structure, pi-pi stacking interactions between the bridging 4-nitrobenzoate
      ligands and the axial pyridine ligand are observed between adjacent molecules.

PMID- 16954635
TI  - Isomorphous crystals of strychninium 4-chlorobenzoate and strychninium 4
      nitrobenzoate.
AB  - In strychninium 4-chlorobenzoate, C21H23N2O2+.C7H4ClO2-, (I), and strychninium 4
      nitrobenzoate, C21H23N2O2+.C7H4NO4-, (II), the strychninium cations form pillars
      stabilized by C-H...O and C-H...pi hydrogen bonds. Channels between the pillars
      are occupied by anions linked to one another by C-H...pi hydrogen bonds. The
      cations and anions are linked by ionic N-H+...O- and C-H...X hydrogen bonds,
      where X=O, pi and Cl in (I), and O and pi in (II).

PMID- 16954636
TI  - 4-(4-fluoro-3-phenoxyphenyl)-6-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3
      carbonitrile and the 6-(4-methylphenyl)- analogue.
AB  - The crystal structures of the title compounds, viz. C24H14F2N2O2, (I), and
      C25H17FN2O2, (II), respectively, have been determined in order to unravel the
      role of an ordered F atom in generating stable supramolecular assemblies. On
      changing the substitution from fluorine to a methyl group, C-H...F interactions
      are replaced by C-H...pi interactions, revealing the importance of such weak
      interactions when present alongside N-H...O and C-H...O hydrogen bonds. The
      dihedral angle between the planes of the 4-fluorophenyl ring and the pyridine
      ring is 26.8 (1) degrees in (I), while that between the planes of the 4
      methylphenyl and pyridine rings is 29.5 (1) degrees in (II).

PMID- 16954637
TI  - 2-anilinomethylene-3-oxobutanenitrile: an X-ray and density functional theory
      study.
AB  - Molecules of the title compound, C11H10N2O, are effectively planar. In the
      crystal structure, they are stabilized primarily by electrostatic interactions,
      as the dipole moment of the molecule is 4.56 D. In addition, the molecules are
      linked by weak C-H...N and C-H...O hydrogen bonds. An analysis of bonding
      conditions in the molecule was carried out using natural bond orbital (NBO)
      formalism.

PMID- 16954638
TI  - Host-guest interaction in a thiourea-dimethyl oxalate (2/1) complex at 300 and
      100 K.
AB  - The title complex, 2CH4N2S.C4H6O4, is a host-guest system. The asymmetric unit
      consists of one complete thiourea molecule and one-half of a dimethyl oxalate
      molecule lying on an inversion centre. The host thiourea molecules are connected
      to form zigzag chains by N-H...S hydrogen bonds. The guest dimethyl oxalate
      molecules provide O-atom acceptors for N-H...O hydrogen bonds, thus
      interconnecting the chains of thiourea molecules to form completely connected
      sheets. The reduction in temperature from 300 to 100 K leaves the structure
      unchanged and still isostructural with that previously determined for the
      analogous thiourea-diethyl oxalate (2/1) complex. It does, however, induce closer
      packing of the molecules, general shrinkage of the unit cell and shortening of
      the hydrogen bonds, these last two to the extent of 1-2%.

PMID- 16954639
TI  - Three substituted (E)-3-aryl-2-(thienyl)acrylonitriles: isolated molecules,
      simple hydrogen-bonded chains and hydrogen-bonded sheets.
AB  - The structure of (E)-2-(2-thienyl)-3-(3,4,5-trimethoxyphenyl)acrylonitrile,
      C16H15NO3S, contains no direction-specific intermolecular interactions. The
      molecules of (E)-3-(4-bromophenyl)-2-(2-thienyl)acrylonitrile, C13H8BrNS, exhibit
      orientational disorder of the thienyl fragment, and the molecules are linked into
      simple C(5) chains by a single C-H...N hydrogen bond. In (E)-3-phenyl-2-(3
      thienyl)acrylonitrile, C13H9NS, the molecules are linked into sheets by a
      combination of one C-H...N hydrogen bond and one C-H...pi(arene) hydrogen bond.

PMID- 16954640
TI  - 5-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)-3-methyl-2-(methylsulfanyl)-6
      phenyl-7H-pyrrolo[2,3-d]pyrimidin-4(3H)-one monohydrate: complex sheets generated
      by multiple hydrogen bonds.
AB  - In the title compound, C22H23N3O3S.H2O, the non-aromatic carbocyclic ring adopts
      a half-chair conformation. The molecules are linked into complex sheets by a
      combination of one N-H...O hydrogen bond and three O-H...O hydrogen bonds.

PMID- 16954641
TI  - 4-dimethylamino-beta-nitrostyrene and 4-dimethylamino-beta-ethyl-beta
      nitrostyrene at 100 K.
AB  - The structures of 4-dimethylamino-beta-nitrostyrene (DANS), C10H12N2O2, and 4
      dimethylamino-beta-ethyl-beta-nitrostyrene (DAENS), C12H16N2O2, have been solved
      at T=100 K. The structure solution for DANS was complicated by the presence of a
      static disorder, characterized by a misorientation of 17% of the molecules. The
      molecule of DANS is almost planar, indicating significant conjugation, with a
      push-pull effect through the styrene skeleton extending up to the terminal
      substituents and enhancing the dipole moment. As a consequence of this
      conjugation, the hexagonal ring displays a quinoidal character; the lengths of
      the C-N [1.3595 (15) A] and C-C [1.448 (2) A] bonds adjacent to the benzene ring
      are shorter than single bonds. The molecules are stacked in dimers with
      antiparallel dipoles. In contrast, the molecule of DAENS is not planar. The ethyl
      substituent pushes the nitropropene group out of the benzene plane, with a
      torsion angle of -21.9 (3). Nevertheless, the molecule remains conjugated, with a
      shortening of the same bonds as in DANS.

PMID- 16954642
TI  - N,N'-bis(2-methoxyphenyl)naphthalene-1,4-dicarboxamide.
AB  - The title compound, C26H22N2O4, crystallizes in an anti-C=O orientation, with the
      two N-substituted benzene rings in different conformations relative to the
      naphthalene ring. These conformations allow two strong N-H...O hydrogen bonds and
      one C-H...pi interaction to generate molecular chains in the cell.

PMID- 16954643
TI  - 4-acetamido-3,3,5,5-[2H4]-2,2,6,6-tetra([2H3]methyl)piperidin-1-yloxyl 0.33
      hydrate.
AB  - The asymmetric unit of the title compound, C11H5D16N2O(2).0.33H2O, is formed by
      three crystallographically independent piperidin-1-yloxyl molecules and a
      molecule of water. The molecules are crosslinked by nine hydrogen bonds into
      layers parallel with the ac plane. The water molecule contributes to the
      stability of the low-symmetry arrangement by four hydrogen bonds.

PMID- 16954644
TI  - L-prolinium picrate and 2-methylpyridinium picrate.
AB  - In the structure of L-prolinium picrate, C5H10NO2+.C6H2N3O7-, the Cgamma atom of
      the pyrrolidine ring has conformational disorder. Both the major and minor
      conformers of the pyrrolidine ring adopt conformations intermediate between a
      half-chair and an envelope. Both the cation and anion are packed through chelated
      three-centred N-H...O hydrogen bonds. The prolinium cation connects two different
      picrate anions, leading to an infinite chain running along the b axis. In 2
      methylpyridinium picrate, C6H8N+.C6H2N3O7-, the cations and anions are packed
      separately along the a axis and are interconnected by N-H...O hydrogen bonds.
      Intramolecular contacts between phenolate O atoms and adjacent nitro groups are
      identified in both structures. A graph-set motif of R1(2)(6) is observed in both
      structures.

PMID- 16954645
TI  - Tris(1,9-diethyladeninium) triiodide diiodide.
AB  - X-ray analysis of the title compound reveals three crystallographically distinct
      cations of 1,9-diethyladeninium, two iodide anions and one triiodide anion in the
      asymmetric unit, giving six residues and the formula 3C9H14N5+.I3-.2I-. Standard
      purine nomenclature is used to identify the atoms of each adenine moiety.
      Hydrogen bonding is observed between atoms N6 and N7 of a pair of cations
      [N...N=2.885 (4)/2.902 (3) and 2.854 (3)/2.854 (3) A], with additional hydrogen
      bonding to I- anions via the other N6 H atom [N...I=3.708 (3), 3.738 (3) and
      3.638 (3) A]. The triiodide anion is not involved in hydrogen bonding. The bond
      lengths and angles of the 1,9-diethyladeninium cations are compared with
      literature values and confirm the formation of the imine tautomer.

PMID- 16954646
TI  - Imino Diels-Alder adducts. XII. Two pyrano[3,2-c]quinolines.
AB  - The crystal structures of pyranoquinolines 9-fluoro-5-phenyl-3,4,4a,5,6,10b
      hexahydro-2H-pyrano[3,2-c]quinoline, C18H18FNO, and 9-methyl-5-phenyl
      3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline, C19H21NO, are isomorphous. In
      both structures, the pyran ring is exo to the six-membered N-heterocyclic ring
      formed in the cycloaddition step. The torsion angles across the phenyl linkage
      for the two structures are -91.2 (1) and -88.3 (2) degrees. The striking feature
      in both crystal packings is that they do not contain the expected conventional
      hydrogen bonds, in spite of the presence of good hydrogen-bonding
      functionalities. Possible C-H...pi interactions are, however, observed.

PMID- 16954647
TI  - Boc-Pro-Hyp-Gly-OBzl and Boc-Ala-Hyp-Gly-OBzl, two repeating triplets found in
      collagen.
AB  - The protected tripeptides benzyl N-{2-[N-(tert-butoxycarbonyl)prolyl]-4
      hydroxyprolyl}glycinate or Boc-Pro-Hyp-Gly-OBzl, C24H33N3O7, and benzyl N-{2-[N
      (tert-butoxycarbonyl)alanyl]-4-hydroxyprolyl}glycinate or Boc-Ala-Hyp-Gly-OBzl,
      C22H31N3O7, are the minimum repeating triplets found in collagen. Within the
      crystal structure of each are two independent peptide molecules with similar
      structures. The peptides are arranged antiparallel to one another and interact
      through hydrogen bonds involving the main chains and the 4-hydroxyprolyl groups.
      The structures exhibit characteristics of a triple helix, but the peptides tend
      to assume a sheet-like structure.

PMID- 16954648
TI  - N-(2-aminobenzyl)-N,N-bis(quinolin-2-ylmethyl)amine.
AB  - The title new diquinaldine derivative, C27H24N4, forms molecular assemblies
      organized by intermolecular quinoline pi-pi stacking [3.356 (3) and 3.440 (3) A]
      and both inter- and intramolecular N-H...N hydrogen bonds [3.039 (3)-3.104 (3) A
      and 129 (2)-172 (2) degrees]. The combination of such interactions provides
      readily definable contacts that propagate along each crystallographic axis.

PMID- 16954649
TI  - Hydrogen-bonded chains in racemic 2-benzyl-3-(2-bromophenyl)propiononitrile and
      hydrogen-bonded sheets in methyl 2-benzyl-2-cyano-3-phenylpropionate.
AB  - The molecules of 2-benzyl-3-(2-bromophenyl)propiononitrile, C16H14BrN, are linked
      into chains by a single C-H...N hydrogen bond. The molecules of methyl 2-benzyl-2
      cyano-3-phenylpropionate, C18H17NO2, are linked into sheets by a combination of C
      H...O and C-H...pi(arene) hydrogen bonds.

PMID- 16954650
TI  - It may take inflammation, phosphorylation and ubiquitination to 'tangle' in
      Alzheimer's disease.
AB  - Neurofibrillary tangles (NFT) are one of the pathologic hallmarks of Alzheimer's
      disease (AD). Their major component is tau, a protein that becomes
      hyperphosphorylated and accumulates into insoluble paired helical filaments.
      During the course of the disease such filaments aggregate into bulky NFT that get
      ubiquitinated. What triggers their formation is not known, but neuroinflammation
      could play a role. Neuroinflammation is an active process detectable in the
      earliest stages of AD. The neuronal toxicity associated with inflammation makes
      it a potential risk factor in the pathogenesis of chronic neurodegenerative
      diseases, such as AD. Determining the sequence of events that lead to this
      devastating disease has become one of the most important goals for AD prevention
      and treatment. In this review we focus on three topics relevant to AD pathology
      and to NFT formation: (1) what triggers CNS inflammation resulting in glia
      activation and neuronal toxicity; (2) how products of inflammation might change
      the substrate specificity of kinases/phosphatases leading to tau phosphorylation
      at pathological sites; (3) the relationship between the ubiquitin/proteasome
      pathway and tau ubiquitination and accumulation in NFT. The overall aim of this
      review is to provide a challenging and sometimes provocative survey of important
      contributions supporting the view that CNS inflammation might be a critical
      contributor to AD pathology. Neuronal cell death resulting from neuroinflammatory
      processes may have devastating effects as, in the vast majority of cases, neurons
      lost to disease cannot be replaced. In order to design therapies that will
      prevent endangered neurons from dying, it is critical that we learn more about
      the effects of neuroinflammation and its products.

PMID- 16954651
TI  - The microbiological and clinical effects of combined therapy according to
      guidelines on the treatment of pulmonary Mycobacterium avium complex disease in
      Japan - including a follow-up study.
AB  - BACKGROUND: The difficulty of treatment for pulmonary Mycobacterium avium complex
      (MAC) in Japan. OBJECTIVES: To investigate the clinical and microbiological
      effects of treatment according to the guidelines proposed by the American
      Thoracic Society and the Japanese Society for Tuberculosis and prospective follow
      up studies after the completion of treatment of patients with pulmonary MAC
      disease. METHODS: Analysis of the microbiological effects with regard to sputum
      conversion rate and the sputum relapsing rate and the clinical effects with
      regard to clinical symptoms and radiological findings for patients with pulmonary
      MAC disease treated with a regimen consisting of rifampicin, ethambutol,
      streptomycin, and clarithromycin over 24 months and follow-up over 12 months.
      RESULTS: Sixty-five patients with pulmonary MAC disease were enrolled in this
      trial. In 39 patients, negative sputum conversion was observed within 6 months
      after the initiation of this regimen, 16 relapsed, and 20 experienced clinical
      worsening within 1 year after the completion of treatment. Although retreatment
      with the same regimen or a regimen including new quinolones was carried out for
      these patients, we could not achieve negative sputum conversion and/or clinical
      improvement. CONCLUSIONS: We believe that the dose of clarithromycin for
      pulmonary MAC disease may be increased and recommend surgery for patients with a
      localized lesion at early-stage MAC disease to prevent a high rate of relapse.

PMID- 16954652
TI  - Association of elevated levels of vascular endothelial growth factor in
      obstructive sleep apnea syndrome with patient age rather than with obstructive
      sleep apnea syndrome severity.
AB  - BACKGROUND: Although certain studies report high levels of vascular endothelial
      growth factor (VEGF) in obstructive sleep apnea syndrome (OSAS), the effect of
      systemic hypoxia on circulating VEGF remains controversial. OBJECTIVES: To study
      the association of serum VEGF and OSAS in a large group of patients. METHODS: One
      hundred patients with OSAS (mean age 58.1+/-12.4 years, mean body mass index
      30.6+/-5.4 kg/m2) were tested for serum VEGF levels, and the findings were
      correlated with the severity of OSAS, as determined by the apnea-hypopnea index
      (AHI) on the basis of polysomnography and background data. RESULTS: The mean AHI
      was 40.0+/-21.2 (range 10-106). Mean minimal oxygen saturation was 80.6+/-11.7%
      (range 43-98%) and mean time of oxygen saturation under 90% was 50.0+/-75.0 min
      (range 0-300 min). The mean VEGF level was 445.2+/-289.8 pg/ml in the study group
      (vs. 280 pg/ml reported in normal controls). The mean platelet count was 233.8+/
      64.4 10(3)/ml and the mean VEGF/platelet ratio was 1.95+/-1.40 pg/10(6). There
      was no association of VEGF or VEGF/platelets with the severity of OSAS. However,
      both factors showed a significant correlation with patient age (r=0.224, p=0.01
      and r=0.425, p=0.01, respectively). Age was the only parameter to significantly
      predict VEGF and VEGF/platelets on multivariate analysis (R2=0.713, p=0.001 and
      R2=0.844, p=0.001, respectively). CONCLUSION: The elevation of serum VEGF in OSAS
      is not associated with the severity of the disease, but it is associated with
      patient age. VEGF might be involved in the long-term adaptive mechanism in OSAS,
      and its age-dependent increase might partly explain the reduced mortality in
      elderly OSAS patients.

PMID- 16954653
TI  - Atypical pneumonia--an uncommon presentation of a well-known disease. Diagnosis:
      Mycobacterium tuberculosis Bronchopneumonia.

PMID- 16954654
TI  - Roflumilast, a phosphodiesterase 4 inhibitor, reduces airway hyperresponsiveness
      after allergen challenge.
AB  - BACKGROUND: Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, is
      currently in clinical development for the treatment of asthma. OBJECTIVES: This
      pilot study examined the effect of roflumilast on allergen-induced airway
      hyperresponsiveness (AHR) to histamine challenge and asthmatic response to
      allergen challenge. METHODS: In a randomized, double-blind, 2-period, crossover
      trial, 13 patients with mild allergic asthma [mean forced expiratory volume in 1
      s (FEV(1)) % predicted = 86%] received a single dose of oral roflumilast 1,000
      microg or placebo. Patients were administered roflumilast 60 min before allergen
      challenge, and asthmatic responses were assessed via change in FEV(1) <or=9 h
      after allergen challenge. AHR to histamine provocation was measured before and
      repeated 24 h after allergen provocation. Patients inhaled histamine in doubling
      concentrations until attaining a decrease in FEV(1) of <or=20% (PC(20)FEV(1)).
      RESULTS: Roflumilast had no detectable bronchodilator activity 60 min after
      administration. Roflumilast significantly attenuated AHR compared with placebo,
      with a mean change in pre- to postallergen challenge PC(20)FEV(1) ratio of 1.23
      +/- 2.75 and 2.51 +/- 2.95 for roflumilast and placebo, respectively (p = 0.002).
      During the late asthmatic response, roflumilast reduced the mean maximum decrease
      in FEV(1) from 2 to 9 h after allergen challenge compared with placebo (p =
      0.005). Additionally, FEV(1) at 9 h after challenge was significantly higher in
      patients treated with roflumilast (p = 0.03). Early asthmatic responses to
      allergen challenge were not significantly reduced by the single dose of
      roflumilast. CONCLUSIONS: Roflumilast attenuated allergen-induced AHR in patients
      with mild asthma. These results support further investigation of roflumilast as
      an anti-inflammatory treatment of asthma.

PMID- 16954655
TI  - Multiplex-FISH (M-FISH): technique, developments and applications.
AB  - Multiplex FISH (M-FISH) represents one of the most significant developments in
      molecular cytogenetics of the past decade. Originally designed to generate 24
      colour karyotyping, the technique has spawned many variations and an equally
      diverse range of applications. In tumour and leukaemia cytogenetics, the two
      groups that have been targeted represent both ends of the cytogenetic spectrum:
      those with an apparently normal karyotype (suspected of harbouring small
      rearrangements not detectable by conventional cytogenetics) and those with a
      complex aberrant karyotype (which are difficult to karyotype accurately due to
      the sheer number of aberrations). In research, mouse M-FISH provides a powerful
      tool to characterize mouse models of a disease. In addition, the ability to
      accurately karyotype single metaphases without selection makes M-FISH the perfect
      tool in chromosome breakage studies and for characterizing clonal evolution of
      tumours. Finally, M-FISH has emerged as the perfect partner for the developing
      genomic microarray (array CGH) technologies, providing a powerful approach to
      gene discovery.

PMID- 16954656
TI  - Spectral karyotyping of human, mouse, rat and ape chromosomes--applications for
      genetic diagnostics and research.
AB  - Spectral karyotyping (SKY) is a widely used methodology to identify genetic
      aberrations. Multicolor fluorescence in situ hybridization using chromosome
      painting probes in individual colors for all metaphase chromosomes at once is
      combined with a unique spectral measurement and analysis system to automatically
      classify normal and aberrant chromosomes. Based on countless studies and
      investigations in many laboratories worldwide, numerous new chromosome
      translocations and other aberrations have been identified in clinical and tumor
      cytogenetics. Thus, gene identification studies have been facilitated resulting
      in the dissection of tumor development and progression. For example, different
      translocation partners of the TEL/ETV6 transcription factor that is specially
      required for hematopoiesis within the bone marrow were identified. Also, the
      correct classification of complex karyotypes of solid tumors supports the
      prognostication of cancer patients. Important accomplishments for patients with
      genetic diseases, leukemias and lymphomas, mesenchymal tumors and solid cancers
      are summarized and exemplified. Furthermore, studies of disease mechanisms such
      as centromeric DNA breakage, DNA double strand break repair, telomere shortening
      and radiation-induced neoplastic transformation have been accompanied by SKY
      analyses. Besides the hybridization of human chromosomes, mouse karyotyping has
      also contributed to the comprehensive characterization of mouse models of human
      disease and for gene therapy studies.

PMID- 16954657
TI  - COmbined Binary RAtio fluorescence in situ hybridiziation (COBRA-FISH):
      development and applications.
AB  - The ability to probe for the location of DNA sequences in morphologically
      preserved chromosomes and nuclei by fluorescence in situ hybridization (FISH)
      provided for cytogenetics a quantum leap forward in resolution and ease of
      detection of chromosomal aberrations. COBRA-FISH, an acronym for COmbined Binary
      RAtio-FISH is a multicolor FISH methodology, which enables recognition of all
      human chromosome arms on the basis of color, thus greatly facilitating
      cytogenetic analysis. It also permits gene and viral integration site mapping in
      the context of chromosome arm painting. Here we review the principle, practice
      and applications of COBRA-FISH.

PMID- 16954658
TI  - Combined multicolor-FISH and immunostaining.
AB  - The combination of multicolor-FISH and immunostaining produces a powerful visual
      method to analyze in situ DNA-protein interactions and dynamics. Representing one
      of the major technical improvements of FISH technology, this method has been used
      extensively in the field of chromosome and genome research, as well as in
      clinical studies, and serves as an important tool to bridge molecular analysis
      and cytological description. In this short review, the development and
      significance of this method will be briefly summarized using a limited number of
      examples to illustrate the large body of literature. In addition to descriptions
      of technical considerations, future applications and perspectives have also been
      discussed focusing specifically on the areas of genome organization, gene
      expression and medical research. We anticipate that this versatile method will
      play an important role in the study of the structure and function of the dynamic
      genome and for the development of potential applications for medical research.

PMID- 16954659
TI  - Proof of partial imbalances 6q and 11q due to maternal complex balanced
      translocation analyzed by microdissection of multicolor labeled chromosomes (FISH
      MD) in a patient with Dandy-Walker variant.
AB  - We report on a family in which a daughter is described with mental retardation,
      as well as malformations of the heart, and of the brain (Dandy-Walker variant).
      The patient's phenotype suggests a chromosomal rearrangement. However, her
      karyotype was unremarkable by conventional cytogenetic analysis. In order to
      detect chromosome rearrangements overseen by this method, the subtelomere regions
      of suspicious chromosomes were verified by fluorescence in situ hybridization
      (FISH). A rearranged derivative chromosome 6 was identified. Further examinations
      by FISH-microdissection (FISH-MD) revealed a maternal complex balanced
      translocation. The patient inherited the derivative chromosome 6 from her mother
      and therefore carries a partial monosomy 6q26-->qter and a partial trisomy
      11q23.3-->qter.

PMID- 16954660
TI  - Multicolor fluorescence in situ hybridization (FISH) applied to FISH-banding.
AB  - During the last decade not only multicolor fluorescence in situ hybridization
      (FISH) using whole chromosome paints as probes, but also numerous chromosome
      banding techniques based on FISH have been developed for the human and for the
      murine genome. This review focuses on such FISH-banding techniques, which were
      recently defined as 'any kind of FISH technique, which provide the possibility to
      characterize simultaneously several chromosomal subregions smaller than a
      chromosome arm. FISH-banding methods fitting that definition may have quite
      different characteristics, but share the ability to produce a DNA-specific
      chromosomal banding'. While the standard chromosome banding techniques like GTG
      lead to a protein-related black and white banding pattern, FISH-banding
      techniques are DNA-specific, more colorful and, thus, more informative. For some,
      even high-resolution FISH-banding techniques the development is complete and they
      can be used for whole genome hybridizations in one step. Other FISH-banding
      methods are only available for selected chromosomes and/or are still under
      development. FISH-banding methods have successfully been applied in research in
      evolution- and radiation-biology, as well as in studies on the nuclear
      architecture. Moreover, their suitability for diagnostic purposes has been proven
      in prenatal, postnatal and tumor cytogenetics, indicating that they are an
      important tool with the potential to partly replace the conventional banding
      techniques in the future.

PMID- 16954661
TI  - Multicolor chromosome bar codes.
AB  - Chromosome bar codes are multicolor banding patterns produced by fluorescence in
      situ hybridization (FISH) with differentially labeled and pooled sub-regional DNA
      probes. These molecular cytogenetic tools facilitate chromosome identification
      and the delineation of both inter- and intra-chromosomal rearrangements. We
      present an overview of the various conceptual approaches which can be largely
      divided into two classes: Simple bar codes designed for chromosome identification
      and complex bar codes for high resolution aberration screening of entire
      karyotypes. We address the issue of color redundancy and how to overcome this
      limitation by complementation of bar codes with whole chromosome painting probes.

PMID- 16954662
TI  - Multicolor banding technique, spectral color banding (SCAN): new development and
      applications.
AB  - Conventional banding techniques can characterize chromosomal aberrations
      associated with tumors and congenital diseases with considerable precision.
      However, chromosomal aberrations that have been overlooked or are difficult to
      analyze even by skilled cytogeneticists were also often noted. Following the
      introduction of multicolor karyotyping such as spectral karyotyping (SKY) and
      multiplex-fluorescence in situ hybridization (M-FISH), it is possible to identify
      this kind of cryptic or complex aberration comprehensively by a single analysis.
      To date, multicolor karyotyping techniques have been established as useful tools
      for cytogenetic analysis. However, since this technique depends on whole
      chromosome painting probes, it involves limitations in that the origin of
      aberrant segments can be identified only in units of chromosomes. To overcome
      these limitations, we have recently developed spectral color banding (SCAN) as a
      new multicolor banding technique based on the SKY methodology. This new technique
      may be deemed as an ideal chromosome banding technique since it allows
      representation of a multicolor banding pattern matching the corresponding G
      banding pattern. We applied this technique to the analysis of chromosomal
      aberrations in tumors that had not been fully characterized by G-banding or SKY
      and found it capable of (1) detecting intrachromosomal aberrations; (2)
      identifying the origin of aberrant segments in units of bands; and (3) precisely
      determining the breakpoints of complex rearrangements. We also demonstrated that
      SCAN is expected to allow cytogenetic analysis with a constant adequate
      resolution close to the 400-band level regardless of the degree of chromosome
      condensation. As compared to the conventional SKY analysis, SCAN has remarkably
      higher accuracy for a particular chromosome, allowing analysis in units of bands
      instead of in units of chromosomes and is hence promising as a means of
      cytogenetic analysis.

PMID- 16954663
TI  - Cryptic terminal chromosome rearrangements in colorectal carcinoma cell lines
      detected by subtelomeric FISH analysis.
AB  - Epithelial tumour karyotypes are often difficult to study by standard cytogenetic
      methods because of poor chromosome preparation quality and the high complexity of
      their genomic rearrangements. Subtelomeric fluorescence in situ hybridisation
      (FISH) has proved to be a useful method for detecting cryptic constitutional
      chromosomal rearrangements but little is known about its usefulness for tumour
      cytogenetic analysis. Using a combination of chromosome banding, multicolour
      karyotyping and subtelomeric FISH, five colorectal cancer cell lines were
      characterised. The resulting data were compared to results from previous studies
      by comparative genomic hybridisation and spectral karyotyping or multicolour
      FISH. Subtelomeric FISH made it possible to resolve several highly complex
      chromosome rearrangements, many of which had not been detected or were
      incompletely characterised by the other methods. In particular, previously
      undetected terminal imbalances were found in the two cell lines not showing
      microsatellite instability.

PMID- 16954664
TI  - Multicolor PRINS and multicolor PNA.
AB  - Both PRimed IN Situ (PRINS) and Peptide Nucleic Acid (PNA) technologies have
      emerged as research techniques, but they have quickly evolved to applications in
      biological diagnosis assays. The two procedures now constitute efficient
      alternatives to the conventional fluorescence in situ hybridization (FISH)
      procedure for in situ chromosome identification and aneuploidy detection. They
      present several advantages (specificity, speed, discriminating ability) that make
      them very attractive for a number of cytogenetic purposes. Multicolor PRINS and
      PNA protocols have been described for the specific identification of human
      chromosomes. Various applications have already been developed in human genetics
      and new adaptations are ongoing.

PMID- 16954665
TI  - Multicolor-FISH applied to resolve complex chromosomal changes in a case of T-ALL
      (FAB L2).
AB  - We report on a patient with a clinically diagnosed acute lymphoblastic leukemia
      (ALL) with partial unrecorded complex translocation events especially involving
      chromosomes 5, 9 and 18. At the GTG-band level the karyotype was abnormal in 20%
      of the analyzed cells. The complex karyotype was studied in more detail by
      spectral karyotyping (SKY) and multicolor banding (MCB) to characterize it in
      more detail. Thus, the karyotype could be described very accurately and in
      summary three different clones were detected, reflecting a high rate of
      karyotypic evolution in this patient.

PMID- 16954666
TI  - Characterization of chromosomal aberrations in diffuse large B-cell lymphoma
      (DLBL) by G-banding and spectral karyotyping (SKY).
AB  - Cytogenetic chromosome analysis by classical G-banding was supplemented by
      spectral karyotyping (SKY) in 12 cases of diffuse large B-cell lymphoma (DLBL).
      SKY is a fluorescence in-situ-based, genome-wide screening technique allowing
      identification of genetic material even in highly condensed metaphase chromosomes
      of poor morphology. By simultaneous hybridization of whole chromosome painting
      probes onto tumor chromosome spreads genetic rearrangements are visualized
      permitting the clarification of even complex karyotype alterations and the
      identification of genetic material of previously unknown origin, so-called marker
      chromosomes. Taking the SKY results into account, we reevaluated the G-banding
      karyotypes initially carried out, thus generating a more precise karyotype in ten
      of twelve (83%) cases investigated. In particular, thirteen chromosomal
      rearrangements not correctly recognized by classical cytogenetics were
      identified, the genetic origin of seven marker chromosomes was elucidated and
      three structural genetic rearrangements were redefined. We found SKY to be a
      valuable technique to establish a definite karyotype in addition to classical
      cytogenetics.

PMID- 16954667
TI  - Multicolor fluorescence in situ hybridization (M-FISH) on cells from urine for
      the detection of bladder cancer.
AB  - Bladder cancer is the fifth most common cancer in adults. Because of the high
      recurrence rate (up to 70%) new tumor markers for urine are necessary for
      monitoring patients. In this study, we investigated the value of M-FISH on cells
      from urine for the detection of bladder cancer. Urine samples from 141 patients
      suspicious of bladder cancer were analyzed in this study. Cells were isolated
      from urine before surgical therapy. For FISH analysis, a commercial kit
      (UroVysion) containing hybridization probes for chromosomes 3, 7, 9p21 and 17,
      was used. Twenty-five cells were analyzed in each case by two observers. A FISH
      result was obtained in 121 cases. Overall, sensitivity was 60% and specificity
      reached 82.6%. Sensitivity and specificity by cytology were 24.1% and 90.5%,
      respectively. Analyzing results concerning T-category, sensitivity of FISH and
      cytology was 36.1% and 15% in pTa, 65.2 and 25.7% in pT1, 100% and 66.7% in pT2-3
      tumors, respectively. Concerning tumor grade, similar results were obtained:
      sensitivity was 37% and 14% in G1, 65.4% and 40% in G2, 91.7% and 50% in G3
      tumors, for FISH and cytology, respectively. In conclusion, FISH on cells from
      urine has been shown in all studies to be highly sensitive and specific for
      detection of bladder cancer. Sensitivity of FISH is higher than conventional
      cytology and can be used in routine diagnosis additionally to conventional
      cytology especially in doubtful or negative cases. FISH can detect recurrence
      earlier than other methods like cytology, cystoscopy or biopsy histological
      examination.

PMID- 16954668
TI  - Molecular cytogenetic characterization of chromosome 9-derived material in a
      human thyroid cancer cell line.
AB  - The incidence of papillary thyroid carcinoma (PTC) increases significantly after
      exposure of the head and neck region to ionizing radiation, yet we know neither
      the steps involved in malignant transformation of thyroid epithelium nor the
      specific carcinogenic mode of action of radiation. Such increased tumor frequency
      became most evident in children after the 1986 nuclear accident in Chernobyl,
      Ukraine. In the eight years following the accident, the average incidence of
      childhood PTCs (chPTC) increased 70-fold in Belarus, 200-fold in Gomel, 10-fold
      in the Ukraine and 50-fold in Tschnigov, Kiev, Rovno, Shitomyr and Tscherkassy
      compared to the rate of about 1 tumor incidence per 106 children per year prior
      to 1986 (Likhtarev et al., 1995; Sobolev et al., 1997; Jacob et al., 1998). To
      study the etiology of radiation-induced thyroid cancer, we formed an
      international consortium to investigate chromosomal changes and altered gene
      expression in cases of post-Chernobyl chPTC. Our approach is based on karyotyping
      of primary cultures established from chPTC specimens, establishment of cell lines
      and studies of genotype-phenotype relationships through high resolution
      chromosome analysis, DNA/cDNA micro-array studies, and mouse xenografts that test
      for tumorigenicity. Here, we report the application of fluorescence in situ
      hybridization (FISH)-based techniques for the molecular cytogenetic
      characterization of a highly tumorigenic chPTC cell line, S48TK, and its
      subclones. Using chromosome 9 rearrangements as an example, we describe a new
      approach termed 'BAC-FISH' to rapidly delineate chromosomal breakpoints, an
      important step towards a better understanding of the formation of translocations
      and their functional consequences.

PMID- 16954669
TI  - Cytogenetic characteristics of a murine in vitro model for the human anaplastic
      large cell lymphoma (ALCL).
AB  - Anaplastic large cell lymphoma (ALCL) is an entity of non-Hodgkin lymphomas (NHL)
      that often occurs in young children and adolescents. In the majority of cases,
      ALCL are of T-cell origin and contain the t(2;5)(p23;q35) leading to an NPM-ALK
      fusion or variant ALK translocations. In addition, there is an ALK-negative
      subtype of ALCL. The anaplastic lymphoid cell line TS1G6 established by
      interleukin (IL)-9 transfection of T-helper cells represents a murine model of
      this subtype. Here, we describe the cytogenetic features of this cell line using
      spectral karyotyping (SKY) and single-color fluorescence in situ hybridization
      (FISH). We show that TS1G6 cells exhibit a hypotetraploid karyotype with complex
      structural alterations. Several unbalanced translocations involved the
      chromosomal region 14E5, and different translocation partners, i.e. X?A6, 3A3 and
      8A1. FISH analysis using a BAC clone containing c-myc confirmed the presence of
      six copies, but also demonstrated that two loci were irregularly located,
      indicating that additional intrachromosomal rearrangements had occurred.
      Moreover, a duplication of the region XF2 approximately 3 was identified.
      Furthermore, six chromosomes 15 were found, representing a trisomy 15 in a
      tetraploid chromosome complement, indicating an altered gene dosage of the
      oncogene c-myc located in region 15D3.

PMID- 16954670
TI  - Interphase M-FISH applications using commercial probes in prenatal and PGD
      diagnostics.
AB  - Early, rapid and reliable diagnosis is of first priority in prenatal medicine.
      The combination of specific sonographic markers (e.g. nuchal translucency) and
      biochemical parameters in maternal serum (e.g. free beta-human chorionic
      gonadotropin, pregnancy-associated plasma protein A), has already dramatically
      improved the sensitivity of non-invasive first trimester risk screening in
      pregnancy. In invasive prenatal diagnosis, in addition to well-established
      chorionic villi short-term culture, interphase multi-colour-fluorescence in situ
      hybridisation (M-FISH) on uncultured amnion cells has become a reliable tool for
      the rapid detection of fetal aneuploidies. Interphase M-FISH applications have
      enabled the diagnosis of selected chromosomal abnormalities in single cells and,
      therefore, have also become an important diagnostic tool for preimplantation
      diagnosis (PGD). The development of commercially available probe sets, in
      particular, has led to a broad use of interphase M-FISH in prenatal and PGD
      diagnosis.

PMID- 16954671
TI  - Molecular cytogenetic studies towards the full karyotype analysis of human
      blastocysts and cytotrophoblasts.
AB  - Numerical chromosome aberrations in gametes typically lead to failed
      fertilization, spontaneous abortion or a chromosomally abnormal fetus. By means
      of preimplantation genetic diagnosis (PGD), we now can screen human embryos in
      vitro for aneuploidy before transferring the embryos to the uterus. PGD allows us
      to select unaffected embryos for transfer and increases the implantation rate in
      in vitro fertilization programs. Molecular cytogenetic analyses using multi-color
      fluorescence in situ hybridization (FISH) of blastomeres have become the major
      tool for preimplantation genetic screening of aneuploidy. However, current FISH
      technology can test for only a small number of chromosome abnormalities and
      hitherto failed to increase the pregnancy rates as expected. We are in the
      process of developing multi-color FISH-based technologies to score all 24
      chromosomes in single cells within a three-day time limit, which we believe is
      vital to the clinical setting. Also, human placental cytotrophoblasts (CTBs) at
      the fetal-maternal interface acquire aneuploidies as they differentiate to an
      invasive phenotype. About 20-50% of invasive CTB cells from uncomplicated
      pregnancies were found to be aneuploid, suggesting that the acquisition of
      aneuploidy is an important component of normal placentation, perhaps limiting the
      proliferative and invasive potential of CTBs. Since most invasive CTBs are
      interphase cells and possess extreme heterogeneity, we applied multi-color FISH
      and repeated hybridizations to investigate the feasibility of a full karyotype
      analysis of individual CTBs. In summary, this study demonstrates the strength of
      Spectral Imaging analysis and repeated hybridizations, which provides a basis for
      full karyotype analysis of single interphase cells.

PMID- 16954672
TI  - Studying meiosis: a review of FISH and M-FISH techniques used in the analysis of
      meiotic processes in humans.
AB  - It is well known that chromosome in situ hybridization allows the unequivocal
      identification of targeted human somatic chromosomes. Different fluorescent in
      situ hybridization (FISH) techniques have been developed throughout the years
      and, following the mitotic studies, meiotic analyses have been performed using
      these different techniques. The introduction of M-FISH techniques to the analysis
      of meiotic cells has allowed the study of meiotic processes for every individual
      human chromosome. In this paper, we review the different FISH and M-FISH
      techniques that have been used on human meiotic cells in both men and women.

PMID- 16954673
TI  - Multicolor FISH used for the characterization of small supernumerary marker
      chromosomes (sSMC) in commercially available immortalized cell lines.
AB  - There are only about 30 commercially available cell lines which include small
      supernumerary marker chromosomes (sSMC). As approximately 2.5 million people
      worldwide are carriers of an sSMC, this small number of immortalized cell lines
      is hard to understand. sSMC cell lines provide practically unlimited material for
      continuing studies e.g. to learn more about marker chromosome formation, or
      karyotypic evolution. To obtain information about their genetic content, in the
      present study we analyzed by FISH and multicolor-FISH approaches 19 sSMC cell
      lines obtained from the European Collection of Cell Cultures (ECACC).
      Microdissection and reverse painting, (sub-) centromere-specific multicolor-FISH
      (sub-)cenM-FISH, multicolor banding (MCB) and selected locus-specific FISH probes
      were applied. Thus, we were able to characterize comprehensively 14 out of 19
      sSMC carrying cell lines; in the remaining five cases an sSMC could not be
      detected. Surprisingly, in six of the nine cell lines with sSMC previously
      characterized for their chromosomal origin by others, those results had to be
      revised. This has impact on the conclusions of previous studies, e.g. for
      uniparental disomy (UPD) in connection with sSMC.

PMID- 16954674
TI  - Molecular cytogenetic identification and characterization of a de novo
      supernumerary neocentromeric derivative chromosome 13.
AB  - We report a young girl with microphthalmia, conductive deafness, aortic isthmus
      stenosis, laryngomalacia, and laryngeal stenosis carrying a de novo supernumerary
      neocentromeric derivative chromosome 13. For the precise identification and
      characterization of the eu- and heterochromatic content of the marker chromosome,
      straightforward molecular cytogenetic analyses were performed, such as chromosome
      microdissection, FISH with different probes (e.g. wcp, alphoid centromeric
      probes, BAC), centromere-specific multicolor FISH (cenM-FISH), and multicolor
      banding (MCB). The analyses demonstrated that the marker consisted of an inverted
      duplication (partial tetrasomy) of the distal portion of chromosome 13 that was
      separated from the endogenous chromosome 13 centromere. Using an all-centromere
      probe and multicolor cenM-FISH, no alpha-satellite DNA hybridization signal was
      detectable on any portion of the derivative chromosome. The presence of a
      functional and active neocentromere on the derivative chromosome 13 was confirmed
      by positive immunofluorescence signals with CENP-C antibodies. BAC-FISH confirmed
      the cytogenetic localization of the neocentromere in band 13q31.3. Thus the
      patient had a mosaic conventional karyotype mos 47,XX,+inv dup(13)(qter-
      >q21.3::q21.3-->q31.3-->neo-->q31.3-->qter)[6]/46,XX [49].

PMID- 16954675
TI  - Supernumerary marker chromosome 5 diagnosed by M-FISH in a child with congenital
      heart defect and unusual face.
AB  - We describe a female patient with a small supernumerary marker chromosome (sSMC)
      present in mosaic and characterized in detail by fluorescence in situ
      hybridization (FISH) using all 24 human whole chromosome painting probes,
      multicolor banding (MCB) and subcentromere specific multicolor FISH (subcenM
      FISH). The sSMC was demonstrated to be derived from chromosome 5 and the
      karyotype of our patient was as follows: 47,XX,+mar.ish r(5)(::p13.2
      approximately p13.3-->q11.2::) [60%]/46,XX [40%]. Partial trisomy for the
      proximal 5p and q chromosomal regions is a rare event. A critical region exists
      at 5p13 for the phenotype associated with duplication 5p. As far as we know,
      eight similar cases have been published up to now. We describe a new case which,
      to our knowledge, is the first characterized in such detail. The role of
      uniparental disomy (UPD) in cases of SMC is also discussed.

PMID- 16954676
TI  - Molecular cytogenetic characterization of a constitutional complex
      intrachromosomal 4q rearrangement in a patient with multiple congenital
      anomalies.
AB  - Constitutional Complex Chromosomal Rearrangements (CCRs) are very rare. While the
      vast majority of CCRs involve more than one chromosome, only seven cases describe
      CCRs with four or more breakpoints within a single chromosome. Here, we present a
      patient with multiple congenital anomalies and mental retardation. Array
      Comparative Genomic Hybridisation (array CGH), FISH and Multicolour Banding FISH
      revealed a de novo complex rearrangement with two deletions, a duplication and an
      inversion of 4q. This CCR involving at least seven breakpoints is one of the most
      complex rearrangements of a single chromosome reported thus far. Potential
      mechanisms generating such complex rearrangements are discussed.

PMID- 16954677
TI  - De novostructural chromosomal imbalances: molecular cytogenetic characterization
      of partial trisomies.
AB  - De novo structural chromosomal imbalances represent a major challenge in modern
      cytogenetic diagnostics. Based solely on conventional cytogenetic techniques it
      may be impossible to identify the chromosomal origin of additional chromosomal
      material. In these cases molecular cytogenetic investigations including
      multicolor-FISH (M-FISH), spectral karyotyping (SKY), multicolor banding (MCB)
      and cenM-FISH combined with appropriate single-locus FISH probes are highly
      suitable for the determination of the chromosomal origin and fine
      characterization of derivative chromosomes. Here we report on four patients with
      de novo chromosomal imbalances and distinct chromosomal phenotypes, three of them
      harboring pure partial trisomies: a mildly affected boy with pure partial trisomy
      10q22.2-->q22.3 approximately 23.1 due to an interstitial duplication, a girl
      with pure trisomy 12p11.21-->pter and atypically moderate phenotype as the
      consequence of an X;autosome translocation, and a girl with multiple congenital
      abnormalities and severe developmental delay and a 46,XX,15p+ karyotype hiding a
      trisomy 17pter-->17q11.1. The fourth patient is a girl with minor phenotypic
      features and mental retardation with an inverted duplication 18q10-->p11.31
      combined with a terminal deletion of 18p32. The clinical pictures are compared
      with previously described patients with focus on long term outcome.

PMID- 16954678
TI  - Duplications of proximal 16q flanked by heterochromatin are not euchromatic
      variants and show no evidence of heterochromatic position effect.
AB  - Extra euchromatic material was found within the major heterochromatic block of
      chromosome 16 (16qh) in one de novo case and seven members of two families. In
      contrast to the euchromatic variants of chromosome 9 (9qh), which are derived
      from pericentromeric euchromatin, molecular cytogenetics confirmed that these
      duplications were of 16q11.2-->q12.2 in the de novo case, of 16q11.2-->q13 in
      three members of family 1 and 16q11.2-->q12.1 in four members of family 2. The
      duplication had arisen as a post-zygotic mitotic event in the mother of family 1
      and been transmitted paternally in family 2. An insertional mechanism of origin
      is proposed for the duplications in case 1 and family 1. Expression at the 16q13
      matrix metalloproteinase-2 (MMP2)locus in families 1 and 2 was proportional to
      genomic copy number and not therefore consistent with position effect silencing
      due to the flanking blocks of heterochromatin. We conclude that proximal 16q
      duplications within 16qh are not novel euchromatic variants but associated with a
      variable phenotype including developmental delay, speech delay, learning
      difficulties and behavioural problems. The behavioural problems in families
      ascertained through affected children are much less severe than those encountered
      in previous patients ascertained as adults.

PMID- 16954679
TI  - A retrospective study of preimplantation embryos diagnosed with monosomy by
      fluorescence in situ hybridization (FISH).
AB  - This report is a retrospective study of preimplantation embryos diagnosed with
      monosomy for chromosomes 13, 15, 16, 18, 21, 22, X and Y on day 3 to determine
      the rate of true positives, false positives and/or mosaicism and to assess if
      these embryos are suitable for in vitro fertilization (IVF) transfer. In a one
      year period, 80 patients went through preimplantation genetic diagnosis for
      aneuploidy screening (PGD-AS). Monosomy was diagnosed in 51 embryos. Fluorescence
      in situ hybridization (FISH) was then performed on the blastomeres at day 5-7
      with commercially available probes using the same probe set that initially
      identified monosomy for chromosomes 13, 16, 21 and 22 or chromosomes 15, 18, X
      and Y. Based on FISH analysis, the monosomy diagnosed during routine PGD-AS
      analysis was confirmed in 17 of the 51 embryos. A euploid result for the specific
      chromosomes tested was observed in 16 of the 51 embryos while mosaicism was found
      in the remaining 18 embryos. This results in an estimated false positive rate of
      3.8% for a diagnosis of monosomy. Reanalysis of these embryos demonstrates that
      the majority of monosomy diagnoses represents true monosomy or mosaicism and
      should be excluded for transfer in IVF. Furthermore, improved understanding from
      recent emerging data regarding the fate of oocytes in women with advanced
      maternal age undergoing IVF to the development of early embryos may provide a
      valuable insight into the mechanism of chromosome mosaicism.

PMID- 16954680
TI  - Towards many colors in FISH on 3D-preserved interphase nuclei.
AB  - The article reviews the existing methods of multicolor FISH on nuclear targets,
      first of all, interphase chromosomes. FISH proper and image acquisition are
      considered as two related components of a single process. We discuss (1) M-FISH
      (combinatorial labeling + deconvolution + wide-field microscopy); (2) multicolor
      labeling + SIM (structured illumination microscopy); (3) the standard approach to
      multicolor FISH + CLSM (confocal laser scanning microscopy; one fluorochrome -
      one color channel); (4) combinatorial labeling + CLSM; (5) non-combinatorial
      labeling + CLSM + linear unmixing. Two related issues, deconvolution of images
      acquired with CLSM and correction of data for chromatic Z-shift, are also
      discussed. All methods are illustrated with practical examples. Finally, several
      rules of thumb helping to choose an optimal labeling + microscopy combination for
      the planned experiment are suggested.

PMID- 16954681
TI  - Rearrangements of chromosome 18 illustrate the utility of array-based comparative
      genomic hybridization.
AB  - Comprehensive and reliable testing is an important component of counseling and
      management in clinical genetics. Identification of imbalances of chromosomal
      segments has uncovered new genes and has established phenotype/genotype
      correlations for many syndromes with previously unidentified causes. Conventional
      cytogenetics has proven to be useful for the detection of large aberrations, but
      its resolution limits the identification of submicroscopic alterations.
      Comparative genomic hybridization (CGH) on a microarray-based platform has the
      potential to detect and characterize both microscopic and submicroscopic
      chromosomal abnormalities. Nine cases of aberrations involving chromosome 18 are
      used to illustrate the use and clinical potential of array CGH.

PMID- 16954683
TI  - Elevated plasma brain natriuretic peptide level in cardiac sarcoidosis patients
      with preserved ejection fraction.
AB  - We sought to examine whether the plasma brain natriuretic peptide (BNP) levels
      are elevated in the cardiac sarcoidosis patients even with a preserved ejection
      fraction. The data from the patients with either pulmonary sarcoidosis without
      any evidence of cardiac involvement (n = 13) or cardiac sarcoidosis (n = 8) with
      a preserved ejection fraction (>55%) on echocardiography were analyzed. The
      median plasma BNP levels were significantly higher in the patients with cardiac
      sarcoidosis than in those with pulmonary sarcoidosis (101.5 +/- 65.1 vs. 15.6 +/-
      10.5 pg/ml, p < 0.001), although there was no significant difference in left
      ventricular ejection fraction between the two populations. The plasma BNP level
      is thus considered to be a useful non-invasive biomarker for identifying a
      possible cardiac involvement in the sarcoidosis patients with a preserved
      ejection fraction.

PMID- 16954682
TI  - Association of RAGE gene polymorphisms with in-stent restenosis in non-diabetic
      Korean population.
AB  - BACKGROUND: Interaction between advanced glycosylation end products (AGEs) and
      receptor for AGEs (RAGE) in vessel wall may lead to inflammation, smooth muscle
      cell proliferation, and extracellular matrix production, culminating in
      exaggerated intimal hyperplasia and restenosis. We investigated the possibility
      that single nucleotide polymorphisms of the genes encoding RAGE are associated
      with in-stent restenosis after coronary stenting. METHODS: Our study included 334
      consecutive non-diabetic male patients with symptomatic coronary artery disease
      who underwent bare metal stent implantation. Follow-up angiography was performed
      in 297 patients (88.9%), 6 months after intervention. We screened -1106T-->C, 
      443T-->C, -388T-->A, -257G-->A, +557G-->A and +1704G-->T RAGE polymorphisms in
      these patients. Genotyping was performed by single base extension with amplifying
      primers and probes for TaqMan. RESULTS: A total of 355 target lesions were
      evaluated, in 297 patients. There was no significant association of the -1106T-
      >C, -443T-->C, -388T-->A, -257G-->A, +557G-->A or +1704G-->T polymorphisms with
      in-stent restenosis after coronary artery stenting. We did not observe a
      significant difference between the genotype distributions and the rates of
      angiographic restenosis between the polymorphisms. In a multivariate analysis of
      angiographic restenosis, we examined the possible influence of the baseline,
      lesion-related, and procedural variables. After adjustment for these potentially
      confounding factors, the multivariate analysis did not reveal an association of
      polymorphism with angiographic restenosis. CONCLUSION: Our observation suggests
      that the RAGE gene polymorphism is not associated with in-stent restenosis after
      coronary artery stenting in non-diabetic patients in the Korean population.

PMID- 16954684
TI  - Inositol-1,4,5-trisphosphate and ryanodine-dependent Ca2+ signaling in a chronic
      dog model of atrial fibrillation.
AB  - Ca2+ signaling regulation plays an important role in triggering and/or
      maintaining atrial fibrillation (AF). Little is known about the relationship of
      the inositol-1,4,5-triphosphate receptors (InsP3Rs) and ryanodine receptors
      (RyRs) in left atrium to chronic AF. In this study, we investigated the
      expression and function of InsP3R1, InsP3R2 and RyR2 in a chronic dog model of
      AF. AF was induced in 6 dogs by rapid right atrial pacing for 24 weeks, and a
      sham procedure was performed in 5 dogs (control group). The intact left atrial
      myocytes were used to examine the expression and function of InsP3Rs, RyRs by
      BODIPY(O,R) TR-X ryanodine, heparin-fluorescein conjugate, and were stimulated by
      caffeine, ATP to release Ca2+ through RyRs, InsP3Rs separately. We also assessed
      the molecular components of left atrial tissue underlying the amount of RyR2,
      InsP3R1 and InsP3R2 determined by RT-PCR, immunohistochemistry and Western blot
      analysis. In the chronic AF group, the Ca2+ released through RyRs is not altered,
      but the Ca2+ released through InsP3Rs increased significantly. RyR2 distributed
      in cytosol of myocytes, cellular membrane; its expression significantly decreased
      in AF group compared to controls. InsP3R1 distributed in cytosol, InsP3R2
      distributed not only in cytosol, cellular membrane, but also in nuclear envelope
      and intercalated discs. The InsP3R1 and InsP3R2 expression significantly
      increased in chronic AF group compared to controls. These results indicated that
      in a chronic dog model of AF, the expression and function of RyR2 down-regulated;
      on the contrary, the expression and function of InsP3R1, InsP3R2 up-regulated,
      and InsP3R2 may be the major InsP3Rs, which regulate intracellular or even
      intercellular Ca2+ signal transmission.

PMID- 16954685
TI  - Multiple episodes of a transient global left ventricular dysfunction reminiscent
      to apical ballooning.
AB  - A new cardiac syndrome with transient left ventricular dysfunction has been
      recently reported and is referred to as Tako-Tsubo cardiomyopathy, which is
      characterized by a transient akinesia of the apex and compensatory basal
      hyperkinesis. Today, the etiology remains unknown. We report for the first time
      of a patient with multiple episodes of a transient global left ventricular
      dysfunction which is reminiscent to apical ballooning. These episodes were always
      preceded by severe emotional stress proposing a potential common pathomechanism.

PMID- 16954686
TI  - Activated mTOR and PKR kinases in lymphocytes correlate with memory and cognitive
      decline in Alzheimer's disease.
AB  - BACKGROUND: The control of translation, involving the kinases mTOR (mammalian
      target of rapamycin) and PKR (double-stranded RNA-dependent protein kinase),
      modulates cell survival and death and is altered in the brains of patients with
      Alzheimer's disease (AD). In AD increased susceptibility of lymphocytes to
      apoptosis has been reported. METHODS: We investigated the level of the kinases
      mTOR and PKR and the eukaryotic initiation factor 2alpha (eIF2alpha) in
      lymphocytes of patients with AD in comparison with controls. In AD patients we
      also looked for a correlation between activated proteins and cognitive and memory
      tests. RESULTS: We report significant alterations of the levels of these kinases
      and eIF2alpha in lymphocytes of AD patients that were also significantly
      correlated with cognitive and memory test scores. CONCLUSION: These results
      suggest that the levels of mTOR, PKR and eIF2alpha in lymphocytes could follow
      the cognitive decline in AD.

PMID- 16954687
TI  - Cognitive-impairment-free life expectancy for Canadian seniors.
AB  - BACKGROUND/AIMS: While cognitive impairment (CI) and dementia are among the most
      common morbid conditions in later life, life expectancies free from CI or
      dementia have been the object of much less investigation than life expectancy
      based on measures of physical functioning. METHODS: We estimated sex-specific CI
      free life expectancy in Canada for people aged 65 and older using data from a
      nationwide, multicenter Canadian study on the epidemiology of dementia. RESULTS:
      The absolute number of years with CI remains virtually constant with increasing
      age. Whatever the current age, senior men can expect to live 2.5-3 years of their
      remaining life with some form of CI and about 1.5 years of those with dementia.
      For women, these figures rise to 3-4 years with CI, of which 2-2.5 years are
      spent with dementia. CONCLUSION: Surviving to an older age does not result in a
      longer average absolute period of CI. This period is associated with a
      significant reduction in quality of life, the use of home and institutional
      services, as well as psychological and physical distress for formal and informal
      caregivers. Results are compared to findings reported in other countries.

PMID- 16954688
TI  - Association of APOE genetic polymorphism with cognitive function and suicide
      history in geriatric depression.
AB  - Apolipoprotein E (APOE) has been associated with a variety of late-life
      neuropsychiatric disorders, including geriatric depression. This study determined
      whether APOE genotypes affect vulnerability to geriatric depression. We also
      tested the effect of the presence of the APOE epsilon4 (APOE4) allele on age of
      onset, suicide attempt history and cognitive function in geriatric depressed
      patients. We genotyped APOE in 111 elderly inpatients diagnosed as having major
      depression and 144 normal controls. The depressed patients were evaluated at
      baseline using the Hamilton Rating Scale for Depression and the Mini-Mental State
      Examination (MMSE) after admission. Age of onset of depression and suicide
      attempt history in the depressed group were evaluated by interview and medical
      record. We found no association between APOE genotypes and geriatric depression
      (p = 0.342) or APOE4 status and age of onset of depression (p = 0.281). However,
      compared with depressed subjects lacking the APOE epsilon4 allele, depressed
      subjects who were also APOE4 carriers showed significantly lower MMSE scores (p =
      0.021) and an increased suicide attempt history (p = 0.012). The APOE genotype
      may contribute to cognitive performance and suicidality in geriatric depression,
      rather than being a specific risk factor for the disorder.

PMID- 16954689
TI  - Effects of cholinergic drugs and cognitive training on dementia: 2-year follow
      up.
AB  - Several studies have shown that pharmacological and cognitive treatments for
      Alzheimers's disease improve cognitive function for short periods, but fewer
      studies have evaluated the efficacy of those treatments for longer (2-year)
      periods. An initial sample of 68 subjects with mild Alzheimer's disease underwent
      clinical and cognitive evaluation. After evaluation, subjects were assigned to
      four different groups and participated in a 2-year follow-up study. Group 1 (n =
      14) received combined drug and cognitive stimulation, group 2 (n = 20) received
      only drug treatment, group 3 (n = 14) received only cognitive stimulation, and
      group 4 (n = 30) received no treatment at all. Results confirmed previous
      investigation, cognitive and combined stimulation improved patients' performance
      throughout the 1st year; however, all groups deteriorated gradually throughout
      the 2nd year of treatment. According to this evidence, it can be concluded that
      we cannot stop cognitive deterioration after 2 years of treatment, although
      deterioration is greater and its progress faster in patients not receiving any
      treatment at all.

PMID- 16954690
TI  - Longitudinal changes of cerebral glucose metabolism in semantic dementia.
AB  - BACKGROUND: Semantic dementia (SD). OBJECTIVE: To identify the pattern of decline
      of cerebral glucose metabolism in SD using cerebral (18)F-fluoro-2-desoxy-D
      glucose positron emission tomography scanning ((18)F-FDG-PET). METHODS: Eight
      patients with SD underwent (18)F-FDG-PET at baseline and at re-examination in
      average 15 months later. RESULTS: Compared with healthy control subjects,
      patients with SD showed a significant asymmetrical (left > right) hypometabolism
      of the temporal lobes, particularly of the anterior poles, at baseline. At follow
      up, we observed a deterioration of cognitive abilities. However, in addition to
      the temporal lobes no other cortical or subcortical region showed a significant
      reduction of glucose metabolism except the anterior cingulate cortex (pcorr <
      0.05). CONCLUSION: Subtle functional changes suffice to produce significant
      neuropsycho- logical deterioration.

PMID- 16954691
TI  - Behavioral disturbances in the course of frontotemporal dementia.
AB  - BACKGROUND: Behavioral disturbances are prominent in frontotemporal dementia
      (FTD), and their occurrence has been the topic of several investigations.
      Nonetheless, the prevalence and severity of behavioral disturbances of patients
      with FTD in different degrees of dementia severity have rarely been studied.
      OBJECTIVE: The aim of this study was to assess and compare the prevalence and
      severity of behavioral disturbances in patients with mild FTD and in patients
      with moderate/severe dementia. METHODS: We included 21 outpatients with mild FTD
      [Clinical Dementia Rating (CDR) = 1] and 19 patients with moderate or severe
      dementia (CDR = 2 or 3) in this study. Behavioral disturbances were assessed
      using the Neuropsychiatric Inventory (NPI). RESULTS: We found a statistically
      significant difference in the total NPI scores between patients with mild FTD and
      patients with moderate or severe FTD, the latter scoring higher. Apathy was the
      most prevalent symptom in both patient groups (90.5 and 100%). Except appetite
      and eating disturbance, which appeared in 77.8% of the patients with
      moderate/severe dementia, all other symptoms were clearly less common (<50%).
      CONCLUSION: The results highlight the variability of behavioral disturbances in
      mild and moderate/severe stages of FTD.

PMID- 16954692
TI  - Plasma homocysteine, cobalamin/folate status, and vascular disease in a large
      population of psychogeriatric patients.
AB  - BACKGROUND: Cobalamin/folate deficiency and vascular disease are prevalent in
      elderly subjects and may lead to mental symptoms, but may even more often
      influence the severity of other organic and non-organic mental diseases. In the
      present study, we have evaluated cobalamin-folate status and the presence of
      vascular disease in 1,982 psychogeriatric patients investigated and diagnosed in
      a psychogeriatric clinic. The objective of the present study is to obtain
      information on the role of cobalamin/folate status and vascular disease in
      different diagnoses of psychogeriatric patients and their association with plasma
      homocysteine (tHcy). METHODS: We have measured serum cobalamin, blood/serum
      folate, serum creatinine, plasma tHcy and evaluated the presence of vascular
      disease in 1,982 well-defined psychogeriatric patients. RESULTS AND CONCLUSIONS:
      The present study indicates that cobalamin/folate deficiencies do not play an
      important role in cognitive dysfunction in psychogeriatric patients, since only
      about 7% of the study population had metabolic cobalamin/folate deficiencies.
      Furthermore, cobalamin/folate deficiencies were rare in younger patients (below
      70 years of age). We were also able to confirm our previous finding that there
      was no association between dementia of Alzheimer type (AD) and plasma tHcy level
      or metabolic cobalamin/folate deficiencies. Furthermore, we observed a low
      proportion of vascular disease in patients with AD, which does not give support
      for an association between well-defined AD and the presence of vascular disease.
      The presence of vascular disease was higher and of similar degree in patients
      with mild cognitive impairment and depression, which indicates an association
      between these diagnoses and the presence of vascular disease. The present study
      also shows that at plasma tHcy levels below 14 micromol/l, the likelihood of
      cobalamin/folate deficiency is small and further investigation of
      cobalamin/folate status could be omitted.

PMID- 16954693
TI  - Influence of premorbid IQ and education on progression of Alzheimer's disease.
AB  - BACKGROUND: Lower education is associated with a higher risk of developing
      Alzheimer's disease (AD). Years of education and measures of general intellectual
      function (IQ) are highly correlated. It is important to determine whether there
      is a relationship between education and AD outcomes that is independent of IQ.
      OBJECTIVE: To test the hypothesis that premorbid IQ is a stronger predictor of
      cognitive decline, global progression, and overall survival, than education in
      patients with AD. METHODS: The study included 478 probable AD patients (322 women
      and 156 men, mean age 74.5 years) followed in a large AD referral center for a
      mean of 3.2 years. Eligible participants had a baseline estimate of premorbid IQ
      using the American version of the Nelson Adult Reading Test (AMNART) and at least
      one follow-up visit with complete neuropsychological assessment. We used random
      effects linear regression analysis, and Cox proportional hazards analysis to
      determine whether or not education and/or premorbid IQ were independently
      associated with cognitive decline, global progression of AD, and survival.
      RESULTS: When the baseline AMNART score was included in regression models along
      with education and other demographic variables, AMNART score, but not education,
      was associated with a higher baseline score and slower rate of decline in MMSE
      and ADAS-Cog scores, and the Clinical Dementia Rating sum of boxes score. Neither
      higher premorbid IQ nor higher education was associated with longer survival.
      CONCLUSIONS: We conclude that a baseline AMNART score is a better predictor of
      cognitive change in AD than education, but neither variable is associated with
      survival after diagnosis.

PMID- 16954694
TI  - Signal transduction pathways mediating CCK-8S-induced gastric antral smooth
      muscle contraction.
AB  - AIM: To investigate the functional and molecular mechanisms by which sulfated
      cholecystokinin octapeptide (CCK-8S) regulates calcium mobilization in gastric
      antral smooth muscle cells (SMCs) of rats. METHODS: Isotonic contraction of
      antral strips was recorded using a polyphysiograph. Immunoprecipitation was used
      to determine the regulatory effect of protein kinase C (PKC) on regulating the
      phosphorylation of the type III inositol 1,4,5-triphosphate receptor (InsP(3)R3)
      in gastric SMCs. Alterations in the intracellular calcium ([Ca(2+)](i))
      concentration were assayed using fura-2/AM-loaded microspectrofluorometry, and
      the L-type calcium current (I(Ca-L)) was recorded by patch-clamp techniques.
      RESULTS: CCK-8S (5 x 10(-8) mol/l) significantly increased the mean contractile
      amplitude of circular muscle by 61.85 +/- 12.67% and the frequency of
      longitudinal muscle by 57.91 +/- 15.70% in gastric antral strips, which were
      suppressed by dexloxiglumide or thapsigargin (TG) and BAPTA-AM (BA). Treatment
      with chelerythrine (5 x 10(-8) mmol/l) significantly inhibited the CCK-8S
      increased phosphorylation of InsP(3)R3 in SMCs. The amplitudes of the CCK-8S
      triggered [Ca(2+)](i) concentration oscillations were reduced in a dose-dependent
      manner when the SMCs were pretreated with increasing concentrations of PMA (from
      10(-8) to 10(-5) mol/l). On removal of extracellular calcium or blocking I(Ca-L)
      by nifedipine, a smaller but significant rise in the [Ca(2+)](i) concentration
      was still elicited by CCK-8S. When [Ca(2+)](i) was depleted by the administration
      of 10(-5) mol/l TG and 10(-5) mol/l BA or blocked by the calcium-dependent
      chloride current (I(Cl-Ca)) by giving 5 x 10(-6) mol/l niflumic acid, the CCK-8S
      intensified I(Ca-L) (from -56.42 +/- 6.57 to -88.54 +/- 5.71 pA) was apparently
      inhibited by 90.34 +/- 4.71% and 82.59 +/- 4.24%. CONCLUSIONS: These results
      demonstrate that the CCK-8S-evoked [Ca(2+)](i) concentration increase in gastric
      antral SMCs depends on the release of [Ca(2+)](i) stores which are negatively
      regulated by PKC-mediated phosphorylation of InsP(3)R3. Released calcium in turn
      activates I(Ca-L) through the activation of I(Cl-Ca), ultimately resulting in the
      contraction of the gastric smooth muscle.

PMID- 16954696
TI  - Nonparametric trend statistic incorporating dispersion differences in sib pair
      linkage for quantitative traits.
AB  - The Haseman-Elston (HE) regression method and its extensions are widely used in
      genetic studies for detecting linkage to quantitative trait loci (QTL) using sib
      pairs. The principle underlying the simple HE regression method is that the
      similarity in phenotypes between two siblings increases as they share an
      increasing number of alleles identical by descent (IBD) from their parents at a
      particular marker locus. In such a procedure, similarity was identified with the
      locations, that is, means of groups of sib pairs sharing 0, 1, and 2 alleles IBD.
      A more powerful, rank-based nonparametric test to detect increasing similarity in
      sib pairs is presented by combining univariate trend statistics not only of
      locations, but also of dispersions of the squared phenotypic differences of two
      siblings for three groups. This trend test does not rely on distributional
      assumptions, and is applicable to the skewed or leptokurtic phenotypic
      distributions, in addition to normal or near normal phenotypic distributions. The
      performances of nonparametric trend statistics, including nonparametric
      regression slope, are compared with the HE regression methods as genetic linkage
      strategies.

PMID- 16954695
TI  - Gene therapy of uterine leiomyoma: adenovirus-mediated herpes simplex virus
      thymidine kinase/ganciclovir treatment inhibits growth of human and rat leiomyoma
      cells in vitro and in a nude mouse model.
AB  - Uterine leiomyomas (LM) affect a high percentage of reproductive-age women. They
      develop as discrete, well-defined tumors that are easily accessible with imaging
      techniques--making this disease ideal for localized gene therapy approaches. In
      this study, we determined the efficacy of adenovirus-mediated herpes simplex
      virus thymidine kinase gene transfer in combination with ganciclovir (Ad-TK/GCV)
      as a potential therapy for LM. Rat ELT-3 LM cells and human LM cells were
      transfected with different multiplicity of infections (10-100 plaque forming
      units [PFU]/cell) of Ad-TK and treated with GCV (5, 10, or 20 microg/ml) for 5
      days. To test the bystander effect, Ad-TK-transfected ELT-3 cells (100 PFU/cell)
      or LM cells (10 PFU/cell) were cocultured with corresponding nontransfected cells
      at increasing percentages and treated with GCV followed by cell counting. In ELT
      3 cells transfected with Ad-TK/GCV (10, 20, 50, or 100 PFU/cell), the cell count
      was reduced by 24, 42, 77, and 87%, respectively, compared with the control cells
      (transfected with Ad-Lac Z/GCV). Similarly, in LM cells transfected with Ad
      TK/GCV (10, 50, or 100 PFU/cell), the cell count was reduced by 31, 62, and 82%,
      respectively, compared with the control. A strong bystander effect was noted in
      both ELT-3 and LM cells with significant killing (p = 0.001) at a ratio of
      infected:uninfected cells of only 1:99 and maximal killing at 1:4. This study
      demonstrates the potential efficacy of the Ad-TK/GCV gene therapy approach as a
      viable nonsurgical alternative treatment for uterine LM.

PMID- 16954697
TI  - Haplotype reconstruction and estimation of haplotype frequencies from nuclear
      families with only one parent available.
AB  - Recent literature has suggested that haplotype inference through close relatives,
      especially from nuclear families can be an alternative strategy in determining
      the linkage phase. In this paper, haplotype reconstruction and estimation of
      haplotype frequencies via expectation maximization (EM) algorithm including
      nuclear families with only one parent available is proposed. Parent and his (her)
      child are treated as parent-child pair with one shared haplotype. This reduces
      the number of potential haplotype pairs for both parent and child separately,
      resulting in a higher accuracy of the estimation. In a series of simulations, the
      comparisons of PHASE, GENEHUNTER, EM-based approach for complete nuclear families
      and our approach are carried out. In all situations, EM-based approach for trio
      data is comparable but slightly worse error rate than PHASE, our approach is
      slightly better and much faster than PHASE for incomplete trios, the performance
      of GENEHUNTER is very bad in simple nuclear family settings and dramatically
      decreased with the number of markers being increased. On the other hand, the
      comparison result of different sampling designs demonstrates that sampling trios
      is the most efficient design to estimate haplotype frequencies in populations
      under same genotyping cost.

PMID- 16954698
TI  - Urine from scrapie-infected hamsters comprises low levels of prion infectivity.
AB  - The question of whether prion diseases can be transmitted by body fluids has
      important epidemiological, environmental and economical implications. In this
      work, we set to investigate whether urine collected from scrapie-infected
      hamsters can transmit fatal or subclinical infectivity to normal hamsters. After
      prolonged incubation times ranging from 300 to 700 days, a small number of
      animals inoculated with scrapie urine succumbed to scrapie disease, and several
      asymptomatic hamsters presented low levels of PrP(Sc) in their brains. In
      addition, most of the asymptomatic hamsters inoculated with scrapie urine, as
      opposed to those inoculated with normal urine, presented extensive gliosis as
      well as protease-resistant light chain IgG in their urine, a molecule shown by us
      and others to be a surrogate marker for prion infection. Our results suggest that
      urine from scrapie-infected hamsters can transmit a widespread subclinical
      disease that in some cases develops into fatal scrapie.

PMID- 16954699
TI  - Genetic variability in CHMP2B and frontotemporal dementia.
AB  - A nonsense/protein chain-terminating mutation in the CHMP2B gene has recently
      been reported as a cause of frontotemporal dementia (FTD) in the single large
      family known to show linkage to chromosome 3. Screening for mutations in this
      gene in a large series of FTD families and individual patients led to the
      identification of a protein-truncating mutation in 2 unaffected members of an
      Afrikaner family with FTD, but not in their affected relatives. The putative
      pathogenicity of CHMP2B mutations for dementia is discussed.

PMID- 16954700
TI  - Unraveling in vivo functions of amyloid precursor protein: insights from knockout
      and knockdown studies.
AB  - The amyloid precursor protein (APP) is a widely expressed transmembrane protein
      that is cleaved to generate Abeta peptides in the central nervous system and is a
      key player in the pathogenesis of Alzheimer's disease. The precise biological
      functions of APP still remain unclear although various roles have been proposed.
      While a commonly accepted model argues that Abeta peptides are the cause of onset
      and early pathogenesis of Alzheimer's disease, recent discussions challenge this
      'Abeta hypothesis' and suggest a direct role for APP in this neurodegenerative
      disease. Loss-of-function studies are an efficient way to elucidate the role of
      proteins and concurrently a variety of in vitro and in vivo studies has been
      performed for APP where protein levels have been downregulated and functional
      consequences monitored. Complete disruption of APP gene expression has been
      achieved by the generation of APP knockout animal models. Further knockdown
      studies using antisense and RNA interference have allowed scientists to reduce
      APP expression levels and have opened new avenues to explore the physiological
      roles of APP. In the present review, we focus on knockout and knockdown
      approaches that have provided insights into the physiological functions of APP
      and discuss their advantages and drawbacks.

PMID- 16954701
TI  - List of drugs in development for neurodegenerative diseases. Update June 2006.

PMID- 16954702
TI  - Ophthalmologic manifestations of cutaneous conditions.
AB  - Many cutaneous conditions have associated ophthalmologic findings, which are
      important to recognize for both dermatologists and ophthalmologists. This review
      highlights some important ophthalmologic manifestations associated with
      neurocutaneous syndromes and inherited connective tissue diseases.

PMID- 16954703
TI  - Efficacy and safety of ab interno excimer laser trabeculotomy in primary open
      angle glaucoma: two years of follow-up.
AB  - Ab interno trabeculotomy was performed using the recently developed XeCl excimer
      laser in 21 eyes of 21 patients with primary open-angle glaucoma refractory to
      medical therapy. The patients were followed at the Eye Department of S. Antonio
      Hospital in Padova, for an average of 25.3 +/- 1.3 months. Intraocular pressure
      (IOP), visual acuity and ocular complications were evaluated. The laser procedure
      was quick and relatively easy, with minimal manipulation of tissues;
      complications were clinically insignificant. At the last follow-up, a marked IOP
      lowering effect compared to baseline was observed (from 24.8 +/- 2.0 to 16.9 +/-
      2.1 mm Hg; -31.8%, p < 0.0001). Nineteen patients (90.5%) had an IOP lowering of
      20% or more; however, 8 of these eyes (38.1%) required additional IOP-lowering
      medical therapy. The procedure failed in 2 cases (9.5%) despite additional
      therapy. In conclusion ab interno excimer laser trabeculotomy seems effective to
      decrease IOP, serves to reduce the number of antiglaucoma medications and is
      relatively safe, proving to be a promising therapeutic option in glaucoma
      surgery.

PMID- 16954704
TI  - Further support for the common variants in complement factor H (Y402H) and
      LOC387715 (A69S) genes as major risk factors for the exudative age-related
      macular degeneration.
AB  - In developed countries, age-related macular degeneration (ARMD) is a common cause
      of blindness in the elderly. It is a clinically complex and genetically
      heterogeneous disorder. The etiology of the disorder may involve interactions
      between genetic and environmental factors. Recently it has been reported that a
      polymorphism in the complement factor H (CFH) and LOC387715 gene may determine
      the susceptibility of individuals to ARMD. In order to replicate and to determine
      the frequency of this polymorphism in ARMD patients, we have analyzed two
      unrelated families having exudative ARMD. Our analysis has identified the same
      common polymorphism (Y402H) in the CFH gene in one family and the A69S
      polymorphism in the LOC387715 gene in the second family. These results further
      support the notion that CFH and LOC387715 genes are the major risk factors for
      ARMD.

PMID- 16954705
TI  - Is there still a clinical use for scanning laser polarimetry with fixed corneal
      compensator?
AB  - PURPOSE: To compare the scanning laser polarimetry device with a fixed corneal
      compensator (GDx FCC) with the new version with a variable corneal compensator
      (GDx VCC) in healthy subjects. METHODS: A prospective, nonrandomized, comparative
      trial was carried out with both the FCC and the VCC systems on 130 healthy
      volunteers. The FCC measurements were divided into 2 subgroups, in accordance
      with the appearance of the macula. Subjects with a uniform aspect of the macula
      were included in the macula-'negative' group (macula-), whereas subjects with an
      irregular macular appearance with FCC were included in the macula-'positive'
      group (macula+). Data relative to all the GDx parameters were examined. For each
      parameter, we compared the data obtained by the FCC to the VCC models.
      Subsequently we compared each FCC subgroup (macula+ and macula-) to VCC. RESULTS:
      A total of 67 subjects entered the macula- group and 63 the macula+ group. FCC
      significantly overestimated the average parameters and underestimated the number,
      the modulation and also the ratio parameters. The only parameter showing no
      difference was symmetry. Similar trends were also evident when the subjects were
      divided into the macula+ and - subgroups. CONCLUSION: Individual variations of
      corneal birefringence, which are not completely corrected by FCC, result in over-
      or underestimation of retinal nerve fiber layer parameters. This measurement
      error cannot be eliminated, not even by only selecting patients with a uniform
      aspect of macular scan. For this reason GDx FCC does not seem to be an acceptable
      tool in the early diagnosis of glaucoma, and modern versions of this device
      should be preferred.

PMID- 16954706
TI  - Corneal curvature after penetrating keratoplasty before and after suture removal:
      a comparison between keratoconus and Fuchs' dystrophy.
AB  - PURPOSE: To assess the differences concerning corneal curvature and visual acuity
      after penetrating keratoplasty (PKP) comparing keratoconus (KC) and Fuchs'
      dystrophy (FUCHS). METHODS: Inclusion criteria for this prospective, comparative,
      interventional study were: (1) one surgeon, (2) central round nonmechanical
      excimer laser PKP without previous surgery, (3) FUCHS (n = 35) or KC (n = 52),
      (4) standardized graft size (7.5-8.0 mm) and technique, 16-bite double running
      cross-stitch suture. In 69% of FUCHS, a triple procedure was performed. The main
      outcome measures were: keratometric astigmatism, surface regularity index,
      surface asymmetry index, keratometric central corneal power and best-corrected
      visual acuity before (1.2 +/- 0.4 years) and after suture removal (1.8 +/- 0.6
      years). RESULTS: Astigmatism did not differ significantly between KC and FUCHS (p
      > 0.1) before (3.3 dpt vs. 3.5 dpt median) and after suture removal (2.5 dpt vs.
      3.0 dpt). Surface regularity index and surface asymmetry index were significantly
      higher in FUCHS than in KC (p < 0.001) at both time stages. Central power was
      significantly greater in KC than in FUCHS (p < 0.001) with sutures in place. Due
      to a significant steepening in FUCHS and flattening in KC, this difference was no
      longer present after suture removal. Visual acuity in KC exceeded that in FUCHS
      before (0.68 vs. 0.60) and even more after suture removal (0.86 vs. 0.60; p <
      0.001). CONCLUSIONS: In KC, keratometric astigmatism is not higher than in FUCHS
      after PKP. After suture removal, graft topography in KC and FUCHS may be expected
      to regularize and the excessive corneal flattening in FUCHS to normalize in the
      mid-term.

PMID- 16954707
TI  - A new technique for pterygium excision: air-assisted dissection.
AB  - PURPOSE: To introduce a new technique which aids to remove the pterygium head and
      facilitates the establishment of a smooth and clear corneal surface without extra
      scraping or polishing. MATERIAL AND METHODS: We used 12 eyes of 12 patients
      undergoing pterygium excision. Air was injected into the side of the cap of the
      pterygium head with a 30-gauge needle, to create a dissection plane between the
      pterygium head and the cornea. After blunt dissection and excision of the
      pterygium, the conjunctival autograft technique was applied. Complications,
      postoperative smoothness and clarity of the cornea, and the recurrence rates were
      evaluated. RESULTS: Dissection with air was successfully performed in 9 eyes
      (75%) in which blunt dissection was carried out easily. The corneas were clear
      and smooth postoperatively. In 3 eyes (25%) dissection with air was not
      completely successful, and scraping with a crescent blade had to be performed.
      One of the eyes with incomplete air dissection could not be clearly scraped. No
      major complications were observed. The recurrence rate was 8.3% (1 eye).
      CONCLUSION: This new technique is a safe, easy and cheap method for removing the
      pterygium head from the corneal surface, which also facilitates the establishment
      of a clear and smooth corneal surface.

PMID- 16954708
TI  - Analysis of an approach to astigmatism correction during cataract surgery.
AB  - PURPOSE: To determine if a system of astigmatic keratomy at the time of cataract
      surgery is safe and effective. SETTING: Academic Ophthalmology Center. METHODS:
      One hundred and ten consecutive patients with greater than 0.50 diopters (d) of
      cylinder with the rule (WTR) and 0.75 d against the rule (ATR) were enrolled.
      Those with an axis between 16 and 74 degrees and 106 and 164 degrees were defined
      as oblique axis. Peripheral clear corneal relaxing incisions 600 mum deep were
      used with a nomogram of 60 degrees length per 1.0 d of attempted correction.
      Keratometry was taken from IOL Master biometry and refractive results at 4-12
      weeks were compared. RESULTS: 60.5% of ATR, 62% of WTR and 23% of oblique
      attempted correction was achieved. Splitting the patients to under and over 70
      years of age had no impact on the results. Of the 14 overcorrected, 7 had oblique
      cylinder (p = 0.009) and 10 had less than 1 d of preoperative cylinder (p =
      0.00015). CONCLUSIONS: Using the IOL Master topography with this nomogram was
      quite effective in reducing preoperative cylinder. Oblique axis results were
      unpredictable, however, and much more likely to lead to an overcorrection.

PMID- 16954709
TI  - Effect of high glucose concentration on corneal collagen biosynthesis.
AB  - The effect of high glucose concentration (3 g/l) on bovine corneal total protein
      and collagen biosynthesis was studied, using 3H-proline incorporation in explant
      cultures with protein and collagen determinations. The high glucose concentration
      increased the incorporation of 3H-proline in total corneal proteins as well as in
      collagens. The specific radioactivity of stromal collagens was strongly increased
      in these conditions. Mannitol was used to control the osmotic effect of the high
      glucose concentration, both at 1 and 3 g/l concentrations. Mannitol did not
      increase the incorporation of 3H-proline in total proteins or collagens, but on
      the contrary decreased it. The high glucose concentration decreased the excretion
      of neosynthesized proteins and collagens in the culture medium, but did not
      affect the total protein or collagen content of the corneas. The strong increase
      in the specific radioactivity of corneal collagens in the presence of 3 g/l
      glucose suggests an increased turnover of collagens in diabetic corneas. The
      increased biosynthesis of collagens together with their decreased elimination in
      the extracellular compartment can create the conditions for the formation and
      accumulation of advanced glycation endproducts by the Maillard reaction. This can
      induce and stimulate the liquefaction of the vitreous body leading to sight
      threatening disorders such as diabetic retinopathy, retinal detachment, glaucoma,
      cataract formation and age-related macular degeneration.

PMID- 16954710
TI  - Pain relief after pterygium surgery with viscous lidocaine.
AB  - PURPOSE: The aim of the current study is to investigate the efficacy of lidocaine
      2% gel for the control of pain experienced after pterygium surgery. METHODS: We
      conducted a prospective, randomized clinical trial on 45 eyes of 45 patients who
      underwent pterygium surgery. The patients were randomized into 2 groups. Group 1
      was provided with topical 2% lidocaine gel and group 2 with artificial tear gel.
      The primary outcome of interest was the pain experienced at the 4th, 7th and 10th
      postoperative hours. Corneal reepithelization was evaluated by slitlamp
      biomicroscopy. Pain was determined using a 10-point linear visual analogue scale.
      No systemic analgesic or topical nonsteroidal anti-inflammatory drop was
      administered. RESULTS: The groups had similar demographic data. The mean pain
      scores of the study and the control groups according to the visual analogue scale
      were: 4.13 +/- 1.86 and 6.50 +/- 1.47 (p = 0.001) at the 4th postoperative hour,
      4.00 +/- 1.16 and 4.00 +/- 1.16 (p = 0.001) at the 7th , and 2.39 +/- 0.89 and
      3.63 +/- 1.00 (p = 0.001) at the 10th postoperative hour, respectively. The mean
      area of the corneal epithelial defect in the lidocaine gel group was 4.78 +/-
      1.04 mm2 and 4.68 +/- 0.89 in the artificial tear gel group (p = 0.42). The mean
      corneal reepithelization time was 37.56 +/- 10.42 h in the lidocaine gel group
      and 34.36 +/- 10.00 h in the artificial tear gel group (p = 0.26). There were no
      side effects related to the drugs observed in either of the 2 treatment groups.
      CONCLUSION: We conclude that topical lidocaine gel is an effective and safe
      anesthetic agent for the control of pain experienced shortly after pterygium
      surgery.

PMID- 16954711
TI  - Clinical study of single-suture inferior retractor repair for involutional
      entropion.
AB  - PURPOSE: To evaluate the clinical efficacy of a simplified single-suture inferior
      retractor repair technique for involutional entropion. METHODS: A retrospective
      study of 20 patients (26 eyelids), followed for 6 months at our hospital, who
      showed no severe horizontal lid laxity were operated on for involutional
      entropion. After subciliary incision, the inferior retractor was identified and
      repaired by reattaching the superior edge of the inferior retractor to the
      inferior edge of the lower tarsus by a single suture using 5-0 prolene. RESULTS:
      26 eyelids of 20 patients (80.8%) were treated successfully without recurrence.
      Complications were seen in 5 eyelids, 2 were overcorrections and 3 were
      recurrences of entropion. Recurred cases were reoperated on and showed good
      postoperative results after the second surgery. CONCLUSIONS: The simplified
      single-suture inferior retractor repair had good results in patients with
      involutional entropion without severe horizontal lid laxity. Moreover, this
      procedure had a short operation and recovery time. In unilateral cases, we could
      achieve more symmetric appearance when compared with bilateral surgeries.

PMID- 16954712
TI  - Effects of latanoprost and betaxolol on cardiovascular and respiratory status of
      newly diagnosed glaucoma patients.
AB  - AIMS: To investigate the cardiovascular and respiratory effects of topical
      latanoprost 0.005% and topical betaxolol 0.25% monotherapy in newly diagnosed
      glaucoma patients. METHODS: Fortynewly diagnosed glaucoma patients were enrolled
      in this prospective, observer-masked, randomized, parallel study. Patients
      received either latanoprost 0.005% or betaxolol 0.25% for a duration of 3 months.
      Baseline evaluation included intraocular pressure (IOP) measurement and
      cardiorespiratory examinations including pulse rate, systolic and diastolic blood
      pressure measurements and spirometry. These measurements were repeated after 3
      months. RESULTS: Both latanoprost and betaxolol reduced IOP significantly (p =
      0.001). After 3 months of therapy, the mean pulse rate, systolic and diastolic
      blood pressure values of the betaxolol group were reduced (p = 0.027, p = 0.07
      and p = 0.016, respectively). No significant changes occurred in the
      cardiovascular measurements of the latanoprost group (p > 0.05). There were no
      significant changes in any of the spirometric measurements tested for both groups
      (p > 0.05). CONCLUSION: Both latanoprost and betaxolol are safe concerning
      respiratory functions. Betaxolol may cause small changes in the cardiovascular
      system, suggesting that blood pressure and pulse rates should be checked before
      and in regular intervals after prescribing it for the elderly. Latanoprost seems
      to be a safe medication in view of absence of systemic cardiovascular and
      respiratory side effects.

PMID- 16954713
TI  - Pharmacokinetic and toxicity investigations of a new intraocular lens with a
      dexamethasone drug delivery system: a pilot study.
AB  - AIM: To investigate the short-term safety and pharmacokinetic behavior of a new
      intraocular lens containing a dexamethasone drug delivery system (IOL-DDS) in
      rabbit eyes. METHODS: A modified polymethylmethacrylate IOL containing a
      biodegradable dexamethasone DDS was implanted into the posterior chamber of the
      right eyes of 9 New Zealand white rabbits. Serial slitlamp and indirect
      ophthalmoscopic examinations (including grading of intraocular inflammation) were
      performed. After 3, 6 and 9 days, the rabbits were euthanized and the globes were
      removed for histological examination and for determination of dexamethasone
      levels in the aqueous humor and in the vitreous. Analysis of dexamethasone
      concentrations was performed by ELISA. RESULTS: Therapeutic concentrations of
      dexamethasone were detectable in the aqueous and vitreous of the study eyes
      throughout the 9-day period in all tested animals. The mean aqueous dexamethasone
      concentration (ng/ml, +/- SD) was 1,015.42 (+/- 43.05), 970.11 (+/- 32.47) and
      757.58 (+/- 30.19) and the mean vitreous concentration (ng/ml, +/- SD) was 399.82
      (+/- 38.05), 287.38 (+/-34.47) and 268.15 (+/- 32.00) at 3, 6 and 9 days after
      the surgical procedure, respectively. No corneal or retinal histological changes
      were observed during the study period. CONCLUSION: The IOL-DDS is effective in
      delivering therapeutic concentrations of dexamethasone to the aqueous and
      vitreous, without acute damage to the cornea and retina. Further controlled
      studies in the same animal model are under way to determine the potential value
      of this lens in the prevention and treatment of inflammation following cataract
      surgery.

PMID- 16954714
TI  - Functional and anatomical findings in acute Purtscher's retinopathy.
AB  - INTRODUCTION: To determine the anatomical location and functional impairment in
      acute Purtscher's retinopathy (PR). MATERIAL AND METHODS: A 15-year-old boy with
      acute PR was examined with optical coherence tomography (OCT) and microperimetry
      (MP). RESULTS: His initial best corrected visual acuity was 20/30 OD and 20/80
      OS, the MP demonstrated absolute scotomas in the central and peripapillary area
      of the cotton-wool spots. On the OCT, there was a hyporeflective area in the
      inner aspect of the retina, corresponding to white patches on funduscopy. After
      he had been treated with oral prednisolone 100 mg, his visual acuity improved to
      20/20 OU within 4 weeks and there were no scotomas on the MP. The central retinal
      architecture returned to normal with no sub- or intraretinal fluid. DISCUSSION:
      Cotton-wool spots in PR represent infarctions of the retinal nerve fiber layer.
      Deeper layers of the retina may also be involved, causing a breakdown of the
      inner blood-retina barrier with temporary intra- and subretinal edema.

PMID- 16954715
TI  - Myoneural junctions of extraocular muscles: distances from the orbital rim and
      widths. Part 2.

PMID- 16954716
TI  - Delayed trigeminocardiac reflex induced by an intraorbital foreign body.

PMID- 16954717
TI  - Intravitreal cortisone injection for refractory diffuse diabetic macular edema.

PMID- 16954719
TI  - Reciprocity and post-trial access for participants in antiretroviral therapy
      trials.

PMID- 16954720
TI  - Specific adaptive humoral response against a gp41 motif inhibits CD4 T-cell
      sensitivity to NK lysis during HIV-1 infection.
AB  - OBJECTIVE: We have recently found that during HIV-1 infection, CD4 T cells
      overexpress a ligand of the NK activating receptor NKp44 (NKp44L) and are
      sensitized to NK lysis. Expression of NKp44L is triggered by a motif (3S) from
      the gp41, highly conserved in all HIV-1 clades. The objectives were to determine
      whether anti-3S antibodies were produced, could counteract 3S-CD4 interactions
      and were correlated to CD4 cell count and NKp44L expression in HIV-infected
      patients. DESIGN: Anti-3S antibodie production was studied in HIV-infected
      patients at various stages of the disease, including a longitudinal study in
      Asymptomatiques a Long Terme (ALT) patients. METHODS: Specimens from 193 HIV-1
      infected patients were examined. Anti-3S antibodies were detected by ELISA, and
      NKp44L expression was analysed by flow cytometry. NK cytotoxicity against
      CD4NKp44L cells was determined in the presence of anti-3S antibodies. RESULTS:
      Anti-3S antibodies were detected in 28.5% of HIV-infected patients. They were
      positively correlated to CD4 cell counts (P = 0.01) and inversely correlated to
      NKp44L expression (P = 0.007). Particularly, in ALT patients, a longitudinal
      study revealed that the CD4 cell count slope differed according to the presence
      or absence of anti-3S antibodies (-0.98 cells/month versus -7.48 cells/month, P >
      0.001). In addition, a clear inhibition of CD4NKp44L NK lysis was observed in
      relationship to anti-3S antibodies titres. CONCLUSIONS: These results strongly
      suggested that anti-3S antibodies might affect disease course in inhibiting
      NKp44L expression and CD4 sensitivity to NK lysis. In linking specific adaptive
      immunity to the innate immunity induced by the 3S motif, this study may have
      important implications for therapeutic vaccines against AIDS.

PMID- 16954721
TI  - CGH of microdissected Kaposi's sarcoma lesions reveals recurrent loss of
      chromosome Y in early and additional chromosomal changes in late tumour stages.
AB  - BACKGROUND: It is still unclear if Kaposi's sarcoma (KS) is a monoclonal cell
      proliferation or a polyclonal, hyperplastic, reactive process. Reports on KS
      cytogenetics are few and restricted to late stage disease and cell lines. METHOD:
      We analysed 27 KS, early and late, AIDS related (AKS) and endemic (EKS) by laser
      microdissection, global DNA amplification and comparative genomic hybridization
      (CGH). RESULT: Loss of Y chromosome was detected in 20/23 male KS, which was the
      only recurrent chromosomal aberration in all nine male early (patch) KS. Only one
      patch EKS showed in addition to the Y loss a loss of Xq. Late (nodular) AKS and
      EKS showed recurrent copy number changes in chromosomes 16, 17, 21, X and Y, as
      well as other random changes. The loss of chromosome 16, 17 and Y was confirmed
      by interphase fluorescence in situ hybridization (FISH) on paraffin sections. EKS
      showed a higher number of chromosomal abnormalities than AKS, indicating that
      rapid growth of AKS is less dependent on genetic changes than is EKS, possibly
      because of the immunosuppressed host environment in AKS. CONCLUSION: Clonal loss
      of chromosome Y was detected in all early male KS, while additional chromosomal
      aberrations appeared during development to late KS. This increase in chromosomal
      abnormalities during tumour growth indicates genetic instability and the
      selection of survival cell clones establishing late, aggressive sarcoma growth.
      Our data support the view that KS (in males) develops into a clonal tumour yet
      initially is a hyperplastic reactive cell proliferation.

PMID- 16954722
TI  - Effects of atazanavir/ritonavir and lopinavir/ritonavir on glucose uptake and
      insulin sensitivity: demonstrable differences in vitro and clinically.
AB  - BACKGROUND: The HIV protease inhibitor (PI) atazanavir does not impair insulin
      sensitivity acutely but ritonavir and lopinavir induce insulin resistance at
      therapeutic concentrations. OBJECTIVE: To test the hypothesis that atazanavir
      combined with a lower dose of ritonavir would have significantly less effect on
      glucose metabolism than lopinavir/ritonavir in vitro and clinically. METHODS:
      Glucose uptake was measured following insulin stimulation in differentiated human
      adipocytes in the presence of ritonavir (2 micromol/l) combined with either
      atazanavir or lopinavir (3-30 micromol/l). These data were examined clinically
      using the hyperinsulinemic euglycemic clamp and oral glucose tolerance testing
      (OGTT) in 26 healthy HIV-negative men treated with atazanavir/ritonavir (300/100
      mg once daily) and lopinavir/ritonavir (400/100 mg twice daily) for 10 days in a
      randomized cross-over study. RESULTS: Atazanavir inhibited glucose uptake in
      vitro significantly less than lopinavir and ritonavir at all concentrations.
      Ritonavir (2 micromol/l) combined with either atazanavir or lopinavir (3-30
      micromol/l) did not further inhibit glucose uptake. During euglycemic clamp,
      there was no significant change from baseline insulin sensitivity with
      atazanavir/ritonavir (P = 0.132), while insulin sensitivity significantly
      decreased with lopinavir/ritonavir from the baseline (-25%; P < 0.001) and from
      that seen with atazanavir/ritonavir (-18%; P = 0.023). During OGTT, the HOMA
      insulin resistance index significantly increased from baseline at 120 min with
      atazanavir/ritonavir and at 150 min with lopinavir/ritonavir. The area under the
      curve of glucose increased significantly with lopinavir/ritonavir but not with
      atazanavir/ritonavir. CONCLUSIONS: Both glucose uptake in vitro and clinical
      insulin sensitivity in healthy volunteers demonstrate differential effects on
      glucose metabolism by the combination PI atazanavir/ritonavir and
      lopinavir/ritonavir.

PMID- 16954723
TI  - Hospitalizations of pregnant HIV-infected women in the USA prior to and during
      the era of HAART, 1994-2003.
AB  - BACKGROUND: The literature on whether HIV infection and its complex
      antiretroviral treatments confer a higher risk for adverse pregnancy outcomes is
      controversial. OBJECTIVE: We compared rates of hospitalization for select
      morbidities among HIV-infected and uninfected pregnant women in the USA. DESIGN
      AND METHODS: Using data from the 1994-2003 Nationwide Inpatient Sample, we used
      descriptive statistics and multivariate logistic regression to examine socio
      demographic characteristics, morbidity outcomes and time trends. RESULTS: There
      were approximately 6000 hospitalizations per year of HIV-infected pregnant women
      in the USA. HIV-infected women were more likely to be hospitalized in urban
      hospitals, in the South, have Medicaid as the expected payer, have longer
      hospitalizations and incur higher charges than uninfected women. Hospitalizations
      for major puerperal sepsis, genitourinary infections, influenza, bacterial
      infections, preterm labor/delivery, and liver disorders were more frequent among
      pregnant HIV-infected women than their uninfected counterparts. However, rates of
      pre-eclampsia and antepartum hemorrhage were not significantly different. While
      rates of inpatient mortality and various infectious conditions decreased between
      1994 and 2003, the rate of gestational diabetes increased among HIV-infected
      pregnant women. CONCLUSIONS: HIV-infected pregnant women in the USA continue to
      be at higher risk for morbidity and adverse obstetric outcomes. With the
      introduction of antiretroviral therapy, rates of most of the conditions examined
      have either decreased or remained stable, hence current antiretroviral regimens
      do not seem to be associated with major adverse pregnancy outcomes on a
      population basis. The increase in gestational diabetes among HIV-infected women
      may be associated, in part, with antiretroviral therapy and merits further
      attention.

PMID- 16954724
TI  - The impact of sex and contraceptive therapy on the plasma and intracellular
      pharmacokinetics of zidovudine.
AB  - OBJECTIVES: Zidovudine remains part of combination antiretroviral therapy.
      Pharmacological studies rely on quantitation of active triphosphates in
      peripheral blood mononuclear cells. This study evaluated the impact of female sex
      and contraceptive therapy on zidovudine plasma and intracellular pharmacokinetics
      and the impact of contraceptive therapy on HIV viral load. METHODS: Serial plasma
      and intracellular zidovudine pharmacokinetics following oral and intravenous
      dosing were determined in 18 men and 20 women treated with zidovudine. Women
      could repeat pharmacokinetics assessment following 2 months oral or injectable
      contraceptive therapy. Zidovudine plasma and intracellular mono-, di- and
      triphosphate concentrations were determined by liquid chromatography tandem mass
      spectrometry. Plasma and cervical viral loads were determined preceding and
      following 2 months of contraceptive therapy in women. RESULTS: Men exhibited
      higher area under the concentration versus time curve for intracellular
      zidovudine and zidovudine-monophosphate following oral and intravenous dosing and
      higher zidovudine triphosphate following oral dosing. There was no difference
      between men and women in plasma zidovudine parameters. Furthermore, contraceptive
      therapy had no effect on zidovudine plasma or intracellular pharmacokinetics or
      on plasma or cervical HIV-1 RNA levels. CONCLUSIONS: Using an optimized
      pharmacokinetic design, this study indicated men exhibit significantly higher
      zidovudine-monophosphate and zidovudine-triphosphate exposure following
      zidovudine oral administration, having implications for drug toxicity and overall
      tolerance of zidovudine therapy. The lack of an effect of contraceptive therapy
      on zidovudine pharmacokinetics is surprising in light of previous pharmacokinetic
      studies for drugs eliminated primarily through glucuronidation. Contraceptive
      therapy had no effect on plasma or cervical viral load, results consistent with
      previous findings.

PMID- 16954725
TI  - Effects of a lifestyle modification program in HIV-infected patients with the
      metabolic syndrome.
AB  - OBJECTIVES: A large percentage of HIV-infected patients receiving HAART develop
      the metabolic syndrome. In this study, we sought to determine whether lifestyle
      modification improves metabolic syndrome criteria, including waist circumference,
      blood pressure, fasting blood sugar, triglycerides, and HDL-cholesterol among HIV
      infected patients with the metabolic syndrome. DESIGN: We conducted a randomized,
      6-month study in HIV-infected patients with metabolic syndrome as defined by the
      National Cholesterol Education Program. Subjects were randomly assigned to an
      intensive lifestyle modification program, which included weekly one-on-one
      counseling sessions with a registered dietician, or observation (control group).
      METHODS: Metabolic syndrome criteria and cardiovascular parameters, including
      blood pressure, body composition, submaximal stress testing, lipids and other
      biochemical parameters were determined. RESULTS: Thirty-four patients were
      randomly assigned and 28 subjects completed the study. Compared with the control
      group, subjects randomly assigned to the lifestyle modification program
      demonstrated significant decreases in waist circumference (-2.6 +/- 1.1 versus
      1.2 +/- 1.0 cm, P = 0.022), systolic blood pressure (-13 +/- 4 versus 4 +/- 4
      mmHg, P = 0.008), hemoglobin A1C (-0.1 +/- 0.1 versus 0.2 +/- 0.1%, P = 0.017),
      lipodystrophy score (-1.2 +/- 0.3 versus 0.9 +/- 0.6, P = 0.006) and increased
      activity (17.7 +/- 14.3 versus -33.1 +/- 12.7 metabolic equivalents, P = 0.014)
      as measured by the Modifiable Activity Questionnaire, but lipid levels did not
      improve. CONCLUSION: These data demonstrate that intensive lifestyle modification
      significantly improved important cardiovascular risk indices in HIV-infected
      patients with the metabolic syndrome. Lifestyle modification may be a useful
      strategy to decrease cardiovascular risk in this population.

PMID- 16954726
TI  - Psychological resources protect health: 5-year survival and immune function among
      HIV-infected women from four US cities.
AB  - OBJECTIVE: Guided by Cognitive Adaptation Theory, the aim was to determine
      whether psychological resources (positive affect, positive expectancy regarding
      health outcomes, finding meaning in challenging circumstances) protect against
      HIV-related mortality and decline in CD4 lymphocyte counts among women with HIV.
      DESIGN: The HIV Epidemiologic Research Study, a longitudinal prospective cohort
      study, with semi-annual interview, physical examination and laboratory assays.
      METHODS: A total of 773 HIV-seropositive women aged 16 to 55 years were recruited
      from four academic medical centers in Baltimore, Maryland; Bronx, New York;
      Providence, Rhode Island; and Detroit, Michigan. Semi-annually for up to 5 years,
      the women were interviewed, underwent physical examination, medical record
      abstraction, and venipuncture. Primary outcomes for these analyses included HIV
      related mortality and CD4 cell count slope decline over 5 years. RESULTS:
      Psychological resources were inversely associated with HIV-related mortality and
      time to death, beyond the effects of potential confounding variables such as
      clinical status (e.g., HIV viral load, symptoms, antiretroviral therapy),
      sociodemographic characteristics (e.g. age, race), and depression at study entry
      (P < 0.05). Psychological resources also were inversely associated with CD4+ cell
      count decline (P < 0.01), serving as a possible mechanism linking resources to
      mortality. CONCLUSIONS: Psychological resources may protect against HIV-related
      mortality and immune system decline. Findings have implications for understanding
      individual variability in HIV disease progression. Moreover, because
      psychological resources are potentially amenable to change, results can be
      applied to clinical interventions aimed at improving the health of women with
      HIV.

PMID- 16954727
TI  - Economic causes and effects of AIDS in South African households.
AB  - OBJECTIVE: To investigate the magnitude and temporal directionality of
      associations between illness and death, and income and expenditure, in households
      affected by HIV/AIDS. DESIGN AND SUBJECTS: A cohort study with repeated measures
      carried out in 405 households (1913 occupants), known to have HIV-infected
      occupants and their neighbours, in one rural and one urban area of South Africa.
      MAIN OUTCOME MEASURES: Monthly adult equivalent income and expenditure. Illness
      episodes and deaths attributed to HIV/AIDS, tuberculosis and pneumonia. METHODS:
      Interview surveys of household heads were conducted at baseline and five more
      times, biannually, providing information on household economics, illnesses and
      deaths. Regression analyses used marginal structural models and 'before-after'
      models to analyse changes. RESULTS: In marginal structural models, current or
      previous AIDS illness was independently associated with 34% [95% confidence
      intervals (CI) 23-43%] lower monthly expenditure, and current or recent poverty
      was associated with 1.74 (95% CI 0.94-3.2) times higher odds of an AIDS death. In
      before-after models, each AIDS death was independently associated with a 23% (95%
      CI 11-34%) greater expenditure decline over 3 years, and a 100 US dollars higher
      monthly expenditure at baseline was associated with 0.31 (95% CI 0.13-0.74) times
      as many AIDS deaths and with 0.41 (95% CI 0.27-0.64) times as many AIDS illness
      episodes over 3 years. CONCLUSION: AIDS deaths and illnesses predicted declining
      expenditure and poverty predicted AIDS, suggesting that both welfare and
      effective treatment are needed.

PMID- 16954728
TI  - Maternal syphilis infection is associated with increased risk of mother-to-child
      transmission of HIV in Malawi.
AB  - OBJECTIVE: To determine the association between maternal syphilis and HIV mother
      to-child transmission (MTCT). DESIGN: Prospective cohort study. METHODS: Pregnant
      women admitted at Queen Elizabeth Central Hospital (Malawi) in late third
      trimester were screened for HIV (by HIV rapid tests) and syphilis (by rapid
      plasma regain test and Treponema pallidum hemagglutination assay). HIV-infected
      women and their infants received nevirapine, according to the HIVNET 012
      protocol. They were followed up at 6 and 12 weeks postpartum. Infant HIV
      infection was diagnosed by DNA PCR. FINDINGS: Of the 1155 HIV-infected women
      enrolled, 1147 had syphilis test results, of whom 92 (8.0%) were infected. Only
      751 HIV-positive women delivered live singleton infants who were tested for HIV
      at birth. Of these, 65 (8.7%) were HIV-infected, suggesting in utero (IU) HIV
      MTCT. Of the 686 infants who were HIV-negative at birth, 507 were successfully
      followed up. Of these, 89 (17.6%) became HIV-infected, suggesting
      intrapartum/postpartum (IP/PP) HIV MTCT. Maternal syphilis was associated with IU
      HIV MTCT, after adjusting for maternal log10 HIV-1 viral load and low birth
      weight (LBW) [adjusted relative risk (ARR), 2.77; 95% CI, 1.40-5.46].
      Furthermore, maternal syphilis was associated with IP/PP HIV MTCT (ARR, 2.74; 95%
      CI, 1.58-4.74), after adjusting for recent fever, breast infection, LBW and
      maternal log10 HIV-1 viral load. CONCLUSION: Maternal syphilis is associated with
      IU and IP/PP HIV MTCT. Screening and early treatment of maternal syphilis during
      pregnancy may reduce pediatric HIV infections.

PMID- 16954729
TI  - CCR5 expression and duration of high risk sexual activity among HIV-seronegative
      men who have sex with men.
AB  - OBJECTIVES: To test the hypothesis that in comparison with those with shorter
      risk duration, individuals with longer HIV risk duration would have reduced
      susceptibility to HIV-1 infection as measured by CCR5 expression, and to evaluate
      whether variation in CCR5 expression could be explained by known genetic
      polymorphisms. DESIGN AND METHODS: A cross-sectional study of HIV-1 exposed but
      uninfected men who have sex with men. The risk duration was estimated from self
      reported years since first receptive anal intercourse. CCR5 expression on
      peripheral blood CD4+ monocytes and T cells was determined by flow cytometry. The
      CCR5-Delta32 mutation and polymorphisms in the CCR5 promoter and CCR2 as well as
      the copy number of CCL3L1 were analyzed by polymerase chain reaction. Plasma
      levels of MIP-1alpha (CCL3), MIP-1beta (CCL4) and RANTES (CCL5) were also
      measured. As risk duration varied with age, analyses were restricted to 67
      individuals aged 30-49 years. RESULTS: Multiple linear regression analyses,
      adjusted for age and race, showed a significant negative association between HIV
      risk duration and CCR5 expression on monocytes (P = 0.01), and in a separate
      model, a similar negative association with CCR5 expression on T cells (P = 0.03).
      Low CCR5 expression was attributable mainly to CCR5-Delta32 heterozygosity and
      the CCR5-59029G allele. CONCLUSIONS: We confirmed a role for reduced CCR5
      expression in HIV-1 resistance. CCR5-Delta32 heterozygosity and the CCR5-59029G
      allele were significant predictors of low CCR5 expression. Individuals with high
      CCR5 expression who resisted infection despite long HIV risk duration form an
      interesting group within which to search for additional mechanisms of resistance
      to HIV infection.

PMID- 16954730
TI  - Lithium improves HIV-associated neurocognitive impairment.
AB  - OBJECTIVE: To determine the effects of low-dose oral lithium on the
      neuropsychological performance of individuals diagnosed with HIV-associated
      neurocognitive impairment. DESIGN AND METHODS: The project was a single-arm, open
      label, 12-week pilot study at a university-based tertiary care center. The
      participants were adults who had been diagnosed with HIV-associated
      neurocognitive impairment and had been on stable antiretroviral therapy for at
      least 12 weeks. Conditions that could affect cognition, worsen adherence to study
      procedures, or increase the risk of lithium adverse reactions were excluded.
      Twenty-one individuals were screened and eight were enrolled, all of whom
      completed the study. Oral lithium was initiated at 300 mg daily and was titrated
      to maintain 12-h trough concentrations between 0.4 and 0.8 mEq/l. Global
      neuropsychological performance was assessed by the global deficit score. RESULTS:
      At baseline, all participants had impaired neuropsychological performance and
      most had reduced CD4 cell counts (median 292 cells/microl), and HIV RNA levels in
      plasma below 400 copies/mL (seven of eight). Titrated lithium doses ranged
      between 600 and 1200 mg/day. Performance improved in all eight individuals after
      12 weeks, and became unimpaired in six. The study treatment was well tolerated
      with no grade 3 or 4 adverse events and no premature discontinuations.
      CONCLUSIONS: Lithium resulted in improved neuropsychological performance in
      antiretroviral-treated, impaired individuals in this small, open-label study.
      Based on published in vitro data, lithium may exert this effect by inhibiting
      neuronal glycogen synthase kinase-3beta.

PMID- 16954731
TI  - Enhancing the potential benefits of HIV post-exposure prophylaxis.

PMID- 16954732
TI  - Antiretroviral activity of didanosine in patients with different clusters of
      reverse transcriptase mutations.
AB  - Patterns of mutations associated with didanosine (ddI) resistance are still a
      controversial issue. The correlation between different clusters of reverse
      transcriptase mutations with the short-term virological activity of ddI when
      added to a failing regimen was examined in 40 patients. The median fall in plasma
      viral load at week 4 was 0.67 log10 copies/ml. There was good correlation between
      the median fall in plasma HIV RNA levels and the number of nucleoside-associated
      (P = 0.0152) or thymidine-associated (P = 0.0142) mutations. In conclusion, ddI
      retained substantial antiretroviral activity when the number of nucleoside
      associated or thymidine-associated mutations was less than four.

PMID- 16954733
TI  - Switching from protease inhibitor-based-HAART to a protease inhibitor-sparing
      regimen is associated with improved specific HIV-immune responses in HIV-infected
      children.
AB  - To evaluate the effects of switching from successful long-term protease inhibitor
      (PI)-based HAART to a three nucleoside reverse transcriptase inhibitor PI-sparing
      regimen, viral load quantification, HIV-specific lymphoproliferative assay and T
      cell receptor (TCR) spectratyping were performed during 96 weeks of
      simplification follow-up in 19 HIV-infected children. Our data showed that
      simplification of therapeutic strategies acts positively on immune competence in
      HIV paediatric patients. Our children maintained viral suppression, increased
      lymphoproliferative responses and normalized TCRBV repertoire on the CD8 subset.

PMID- 16954734
TI  - Viral failure in HIV-infected patients with long-lasting viral suppression who
      discontinued enfuvirtide.
AB  - The aim of this pilot study was to assess whether enfuvirtide can be discontinued
      in patients on long-term viral suppression. Eight patients with multidrug
      resistant virus were randomly assigned to stop and 10 subjects to continue
      enfuvirtide. At week 48, viral rebound occurred in five (62.5%) and in no
      patients, respectively, (P = 0.007). The CD4 cell decrease in failure patients
      was 5% (P = ns). These results suggest that enfuvirtide should be maintained
      until new active drugs became available.

PMID- 16954735
TI  - Is HIV out of control in the UK? An example of analysing patterns of HIV
      spreading using incidence-to-prevalence ratios.
AB  - The incidence of diagnosed HIV in the UK is increasing. We calculated the
      incidence-to-prevalence ratio, IPR(t), which must exceed an 'epidemic threshold',
      the reciprocal of the mean infectious period, for sustained transmission to
      occur. For heterosexuals the IPR(t) is too low for a self-sustained UK epidemic,
      and incidence is driven by increasing prevalence, mostly from imported cases. For
      men who have sex with men the IPR(t) is around the epidemic threshold, suggesting
      that spread is not yet under control.

PMID- 16954736
TI  - Terminal ileitis as a manifestation of immune reconstitution syndrome following
      HAART.

PMID- 16954737
TI  - HIV-contaminated syringes are not evidence of transmission.

PMID- 16954738
TI  - Severe vitamin D deficiency diagnosed after introduction of antiretroviral
      therapy including efavirenz in a patient living at latitude 59 degrees N.

PMID- 16954739
TI  - Contribution of platelet activation to plasma IL-18 concentrations in HIV
      infected AIDS patients.

PMID- 16954741
TI  - Lifting devices revisited: Safer for nurses--but what about the patients?

PMID- 16954742
TI  - Workplace safety.

PMID- 16954744
TI  - Untapped power.

PMID- 16954747
TI  - The ANA and AJN.

PMID- 16954749
TI  - Placebo use in the N-of-1 trial.

PMID- 16954754
TI  - Adherence to HIV Regimens: A tailored nursing intervention fails to motivate one
      clinic's patients.

PMID- 16954757
TI  - The health legacy of September 11: Five years later, illnesses and memories haunt
      many.

PMID- 16954759
TI  - APIC conference update: Infection control specialists and epidemiologists
      converge.

PMID- 16954760
TI  - Avian influenza family cluster: Major mutation hasn't yet taken place.

PMID- 16954761
TI  - The shape of things to come?: RNs nationwide share their perspectives on health
      care reform at working group's meetings.

PMID- 16954762
TI  - Stage 4 chronic kidney disease: Preserving kidney function and preparing patients
      for stage 5 kidney disease.

PMID- 16954765
TI  - Making the decision to report to work in a disaster: Nurses may have conflicting
      obligations.

PMID- 16954766
TI  - The ethical dilemma: Questions to consider when deciding whether to show up for
      work in a disaster.

PMID- 16954767
TI  - Effects of nursing rounds: on patients' call light use, satisfaction, and safety.
AB  - OBJECTIVE: There is limited research on patient call light use as it pertains to
      effective patient-care management, patient safety, and patient satisfaction.
      Therefore, this study sought to determine the frequency of and reasons for
      patients' call light use, the effects of one-hour and two-hour nursing rounds on
      patients' use of the call light, and the effects of such rounding on patient
      satisfaction, as well as patient safety as measured by the rate of patient falls.
      METHODS: A six-week nationwide study was performed using a quasi-experimental
      nonequivalent groups design; baseline data was taken during the first two weeks.
      Analyses were performed on data from 27 nursing units in 14 hospitals in which
      members of the nursing staff performed rounds either at one-hour or two-hour
      intervals using a specified protocol. RESULTS: Specific nursing actions performed
      at set intervals were associated with statistically significant reduced patient
      use of the call light overall, as well as a reduction of patient falls and
      increased patient satisfaction. CONCLUSIONS: A protocol that incorporates
      specific actions into nursing rounds conducted either hourly or once every two
      hours can reduce the frequency of patients' call light use, increase their
      satisfaction with nursing care, and reduce falls. Based on these results, we
      suggest operational changes in hospitals, emphasizing nurse rounding on patients
      to achieve more effective patient-care management and improved patient
      satisfaction and safety.

PMID- 16954774
TI  - Supporting parents after stillbirth or newborn death: There is much that nurses
      can do.

PMID- 16954775
TI  - What have my kidneys got to do with my sex life?: The impact of late-stage
      chronic kidney disease on sexual function.

PMID- 16954776
TI  - Ask not what nursing can do for you ...: Nurses have a lot of power.

PMID- 16954777
TI  - The nurse competence in aging initiative: Encouraging expertise in the care of
      older adults.

PMID- 16954778
TI  - Picking up the pieces: Katrina may be a memory, but nursing's recovery is far
      from complete.

PMID- 16954779
TI  - Does workplace stress lead to accident or error?: Many nurses feel the pressure.

PMID- 16954781
TI  - Maternal asthma during pregnancy and fetal outcomes: potential mechanisms and
      possible solutions.
AB  - PURPOSE OF REVIEW: Asthma exacerbations during pregnancy can be a serious
      complication that have detrimental consequences for both mother and fetus. The
      pathophysiological mechanisms that cause worsening asthma during pregnancy are
      only just starting to be examined. This review will examine the recent literature
      on immune function in pregnant women, immune function in nonpregnant asthma
      patients and studies conducted on asthma during pregnancy. RECENT FINDINGS: Fifty
      five percent of women with asthma will experience at least one exacerbation
      during pregnancy. This has significant effects on fetal growth and survival,
      especially if the fetus is male. A number of factors that may contribute to the
      development of worsening asthma during pregnancy include pregnancy-induced
      changes in maternal immune function, increased maternal susceptibility to
      infection, female fetal sex, noncompliance with medication and prepregnancy
      asthma severity. Interestingly, the immune changes in the maternal system in
      response to the presence of the fetus and placenta are very similar to the immune
      changes described in nonpregnant asthma patients with noneosinophilic asthma.
      SUMMARY: These studies highlight that worsening asthma during pregnancy cannot be
      attributed to pregnancy alone or asthma alone and may be a complex combination of
      factors and events.

PMID- 16954782
TI  - The effects of in-utero tobacco-toxin exposure on the respiratory system in
      children.
AB  - PURPOSE OF REVIEW: Promotion of cigarettes to children and women has resulted in
      unacceptably high rates of smoking during pregnancy in most developed countries
      and the potential to greatly increase smoking by mothers in developing countries.
      The risks of smoking during pregnancy to mothers and unborn children are well
      known and include growth retardation, respiratory diseases and sudden infant
      death syndrome. Determining the effects of exposure on the fetus depends upon
      accurate assessment of maternal smoking, both active and involuntary, and this
      can be done using self-reports and a variety of biomarkers in the mother and/or
      newborn. RECENT FINDINGS: The evidence is clear that most of the excess
      respiratory morbidity in children born to smoking mothers is due to in-utero
      exposure and that deficits in lung function measured soon after birth persist in
      children and adults. Recent studies have also indicated that some children are
      genetically predisposed to adverse outcomes in response to in-utero exposure.
      SUMMARY: Although many women attempt to quit during pregnancy and effective
      interventions are available, ultimately the respiratory health of future
      generations will depend upon effective public health and tobacco control measures
      designed to prevent smoking uptake by youth and in particular girls and young
      women.

PMID- 16954783
TI  - Variations in genetic influences on the development of asthma throughout
      childhood, adolescence and early adult life.
AB  - PURPOSE OF REVIEW: Asthma is likely to be due to many aetiological factors, the
      effect of each varying considerably with age. Now that there are well established
      candidate genes for asthma, using genetics to examine age-related susceptibility
      to asthma offers a new approach to understanding the basic underlying mechanisms.
      RECENT FINDINGS: Since few long-term, longitudinal asthma studies exist,
      opportunities to examine age-related genetic susceptibility have been limited,
      but have produced some specific findings. The CCR5Delta32 polymorphism renders
      the chemokine receptor nonfunctional and is associated with reduced asthma
      susceptibility in children but not adults. In CD14 C-159T, the -159C allele has
      been associated with increased atopy in mid-childhood, but not in young adults.
      IL-12beta is a promoter polymorphism associated with reduced lung function in
      girls but not boys in mid-childhood only. Regarding the beta(2)adrenoceptor,
      results from three studies suggest that Arg16 can be associated with impaired
      airway function in infancy and Gly16 with asthma and wheeze in mid-childhood.
      SUMMARY: Age-related genetic susceptibility studies are likely to make a major
      contribution to understanding basic mechanisms in asthma, but the limited number
      of suitable cohorts has meant that to date few studies have been reported.

PMID- 16954784
TI  - Gene-environment interactions in the development of chronic obstructive pulmonary
      disease.
AB  - PURPOSE OF REVIEW: Genetic factors influence the variable development of chronic
      obstructive pulmonary disease in response to smoking and are likely to vary
      between populations. Recent studies have begun to shed some light on these gene
      environment interactions. RECENT FINDINGS: A variety of approaches has been used
      to identify novel susceptibility genes for chronic obstructive pulmonary disease.
      These studies have provided evidence for the possible role of many inflammatory
      mediators and their receptors, proteases, antiproteases, and antioxidant and
      xenobiotic genes in chronic obstructive pulmonary disease pathophysiology.
      However, ethnic differences and subtle phenotype differences often make
      replication of these studies difficult. SUMMARY: The completion of the Human
      Genome Project, the HapMap project, technological advances in single-nucleotide
      polymorphism genotyping and the potential of genome-wide association analysis
      will allow the identification of susceptibility genes for chronic obstructive
      pulmonary disease. The challenge is to understand the influence of multiple
      genetic factors and multiple environmental factors as well as gene-gene and gene
      environment interactions. Careful clinical characterization of phenotypes for
      chronic obstructive pulmonary disease is essential and this will include
      comparison of biomarkers of distinct pathologies including radiological
      assessment to separate the components of pulmonary emphysema and small-airway
      disease.

PMID- 16954785
TI  - Interaction of keratinocytes with infiltrating lymphocytes in allergic eczematous
      skin diseases.
AB  - PURPOSE OF REVIEW: Eczematous skin diseases, including atopic dermatitis, are
      characterized by T-cell infiltration into the epidermal compartment. Whereas an
      active role of the main constituents of the epidermis, the keratinocytes, has
      long been neglected, it has become clear in the last decade that they are
      important, immunological active cells. This review highlights the recent work
      published between March 2005 and May 2006 that expands our knowledge about
      keratinocyte-T-cell interactions in epidermal immune responses, with emphasis on
      the pathogenesis of eczematous skin diseases in humans, mainly atopic dermatitis.
      RECENT FINDINGS: The cross-talk between T cells and keratinocytes is only
      partially understood. Recent studies suggest that in certain micromilieu
      settings, keratinocytes are capable of regulating the response of CD4+, CD8+ as
      well as regulatory T cells. Keratinocytes, however, respond to T helper type 1
      and type 2-derived mediators which often exert synergistic effects on these
      cells. So far, only very few studies have investigated how T-cell-keratinocyte
      interaction influences the outcome of inflammatory responses in autologous human
      systems. SUMMARY: Keratinocytes play an active part during the acute and the
      chronic phase of eczema by means of cytokine production and surface molecule
      expression which leads to an inflammatory infiltrate in the upper layers of the
      skin.

PMID- 16954786
TI  - Anxiety in allergy and atopic dermatitis.
AB  - PURPOSE OF REVIEW: Individuals suffering from allergies often exhibit a specific
      psychological profile characterized by anxiety, depression and emotional
      excitability. Emotional stress precipitates allergic symptoms not only by
      heightening anxiety levels but also by dysregulating immune-cell functions. The
      primary objective of this report is to review recent findings of the relationship
      between anxiety and hypersensitivity responses in the context of
      psychoneuroimmunology in allergic individuals, notably patients with atopic
      dermatitis. RECENT FINDINGS: Atopic subjects with emotional problems develop a
      vicious cycle between anxiety and clinical symptoms. Acute stresses, which
      repeatedly and chronically affect patients with atopic dermatitis, raise anxiety
      in general more preferentially than anxiety at present. This psychological
      failure enhances Th2-type responses due to dysregulation of the neuroimmune
      system, leading to worsening of allergic symptoms. Tandospirone, a 5
      hydroxytryptamine 1A receptor agonist with anxiolytic and antidepressant effects,
      attenuates itching through successful control of emotional difficulties. These
      data suggest the efficacy of administrating drugs with anxiolytic effects as part
      of the management strategy of stress-associated itching in patients with atopic
      dermatitis. SUMMARY: Psychological interventions such as periodic monitoring of
      anxiety levels in the context of immune functions and skin conditions are
      fundamental in therapy of allergic patients with emotional problems.

PMID- 16954787
TI  - Patch testing: pitfalls and performance.
AB  - PURPOSE OF REVIEW: Contact dermatitis is a common disease process that includes
      allergic and irritant contact dermatitis. The gold standard for diagnosing
      allergic contact dermatitis, a type IV delayed hypersensitivity reaction, is
      patch testing. Patch testing is not a difficult procedure, however, there are
      several critical components that determine the success of the test: having an
      appropriate level of suspicion for the diagnosis of allergic contact dermatitis,
      an adequate threshold for patch testing, the necessary experience to properly
      interpret the results and to determine their relevance, and the ability to
      thoroughly educate the patient about the condition. RECENT FINDINGS: Research
      shows that patch testing practices differ among individuals and specialties. The
      level of patch testing education, interest in, and experience with, the procedure
      can affect the results of the test. Some of these practice differences and how
      they affect the outcome of patch testing are highlighted. SUMMARY: Physicians'
      knowledge and experience with patch testing, their level of interest and access
      to allergens will determine the performance of this test, the reliability of the
      results and the benefits gained from this procedure.

PMID- 16954788
TI  - Steroids versus other immune modulators in the management of allergic dermatoses.
AB  - PURPOSE OF REVIEW: The classic role of topical and systemic corticosteroids for
      allergic dermatoses is discussed, with special attention to the impact on the
      current clinical treatment paradigm by newer systemic and topical therapies.
      These products are reviewed and recommendations presented on how to effectively
      assimilate them into clinical practice. RECENT FINDINGS: Current knowledge about
      the etiopathogenesis of atopic dermatitis has resulted in drug development
      focused on agents with less toxicity than current topical and systemic
      corticosteroids. Some agents with ceramide/cholesterol/acid combinations
      demonstrate efficacy in restoring the dysfunctional skin barrier of atopic
      patients. Concerns resulting from the recent Federal Drug Administration
      announcement regarding a theoretical risk of cancer associated with topical
      calcineurin inhibitors are also addressed. Novel therapeutic entities are
      presented. SUMMARY: Patients seeking relief from atopic dermatitis have
      historically had few really effective and safe therapeutic options. Topical
      calcineurin inhibitors represent an exciting new therapy for atopic dermatitis
      without the side-effect profile associated with topical corticosteroids.
      Nonsteroidal formulations incorporating glycyrrhetinic acid/telmesteine/Vitis
      vinifera extract and palmitoylethanolamide as 'active' ingredients recently
      entered the market, stressing antipruritic, antiinflammatory, and skin barrier
      repair. This confabulates against previously designed topical therapy paradigms.
      These new products may be used as monotherapy or alternatives to steroid agents.

PMID- 16954789
TI  - Vasomotor (perennial chronic) conjunctivitis.
AB  - PURPOSE OF REVIEW: To increase the awareness of nonimmunoglobulin E-mediated
      conjunctival disorders similar to those recognized to affect other organs that
      are targets in immunoglobulin E-mediated disorders. Such conditions may include
      'vasomotor' instability, that is vasomotor conjunctivitis, which leads to a more
      common perennial chronic conjunctivitis. These conditions are not commonly
      included in the differential diagnosis of allergic conjunctivitis. RECENT
      FINDINGS: Although there have not been specific recent findings regarding the
      eye, it appears that evidence for such disorders in the rhinitis literature
      suggests that they can be involved in more than 25% of chronic conjunctivitis
      cases. The extrapolation of such conditions to the conjunctival surface clearly
      reflects these syndromes which have clearly been underappreciated and
      underdiagnosed. SUMMARY: A significant amount of work remains to be performed to
      understand perennial chronic conjunctivitis (vasomotor conjunctivitis or
      nonallergic noninfectious conjunctivitis) as well as other forms of chronic
      conjunctivitis that can mimic or exist in a comorbid state with ocular allergy.
      These disorders need to be better defined, categorized and classified to
      determine the best treatment modalities. Management guidelines and parameters of
      chronic noninfectious conjunctivitis need to be set on a national and
      international basis that will advance clinically applicable research results,
      pharmaceutical development and relief for patients.

PMID- 16954790
TI  - Role of suppressor of cytokine signaling in ocular allergy.
AB  - PURPOSE OF REVIEW: The goal of this article is to evaluate developments in the
      knowledge of suppressor of cytokine signaling (SOCS) protein ocular allergy and
      the potential of SOCS proteins as targets for therapeutic strategies. RECENT
      FINDINGS: The family of proteins designated SOCS proteins plays an important role
      in Th2-mediated allergic responses through the control of the balance between Th1
      and Th2 cells. SOCS3 and SOCS5 are predominantly expressed in Th2 and Th1 cells,
      respectively, and they reciprocally inhibit the Th1 and Th2 differentiation
      processes. SOCS3 is highly expressed at the disease site of allergic
      conjunctivitis, and T-cell-specific expression of SOCS3 deteriorates clinical and
      pathological features of allergic conjunctivitis. Reduction of the expression
      level or inhibition of function clearly reduces the severity of allergic
      conjunctivitis. On the other hand, constitutive expression of SOCS5, a specific
      inhibitor of IL-4 signaling, results in reduced eosinophil infiltration.
      Moreover, negative regulation of the Th2-mediated response by dominant-negative
      SOCS3 and SOCS5 reduced the incidence of allergic conjunctivitis in a mouse
      model. SUMMARY: The present article summarizes recent findings in terms of a role
      of SOCS protein as a negative regulator in ocular allergy and its clinical
      application.

PMID- 16954791
TI  - Ocular toxicology: the Draize eye test.
AB  - PURPOSE OF REVIEW: Superficial ocular tissues are frequently exposed to damage
      produced by chemical compounds applied on or around the ocular surface for
      cosmetic, therapeutic or accidental reasons. An experimental test measuring
      objectively and in a reproducible way any potential damaging effect would
      certainly help in prospectively minimizing unwanted effects. The Draize eye test,
      although commonly employed to date, does not seem to be quite satisfactory in
      this respect. RECENT FINDINGS: The limits of the Draize eye test and the results
      of some modified versions of the test are analysed. In particular, the good
      predictivity of the so-called low-volume Draize eye test and the recent findings
      of studies on the in-vitro and ex-vivo alternatives to the Draize eye test are
      presented. SUMMARY: The Draize eye test, despite criticisms, has been used in the
      clinical setting for a long time and still remains the reference protocol. To
      date, only a combination of alternative methods, none of which is devoid of
      serious criticisms, seems to be able to exhaustively recognize potential
      irritants and avoiding for that purpose, in some cases, the use of living
      animals.

PMID- 16954792
TI  - Ocular cicatricial pemphigoid.
AB  - PURPOSE OF REVIEW: To review the content and importance of articles on ocular
      cicatricial pemphigoid (OCP), or mucous membrane pemphigoid (MMP) with relevance
      to ocular involvement, published from 2005 to 2006. RECENT FINDINGS: There is
      wide antigenic heterogeneity in MMP and OCP and attempts are being made to link
      this with clinical variations with varying degrees of success. A larger study
      demonstrates a link between multiple autoantibody reactivity and disease
      severity. Details of epitope specificity are emerging. A highly sensitive ELISA
      for laminin 5 has been developed which may provide prognostic
      information.Clinically, younger OCP patients show more severe ocular disease and
      are less well controlled by medication. A systematic review shows good evidence
      only for steroids and cyclophosphamide in OCP. Continued small trials suggest
      some role for the expensive intravenous immunoglobulin therapy in OCP where
      conventional treatment fails. Ocular reconstruction surgery has made some
      progression, and is enhanced by adjunctive medical therapy; osteo-odonto
      keratoprosthesis offers some hope of prolonged retention of limited vision in end
      stage disease. SUMMARY: OCP remains a difficult disease to manage well and the
      progress being made in understanding disease mechanisms is whence true disease
      modifying, safe therapy is likely to emerge in the future.

PMID- 16954793
TI  - Muscarinic receptors in the ocular surface.
AB  - PURPOSE OF REVIEW: A wide distribution of the eye's muscarinic receptor system
      has been found and several roles for the muscarinic system in the eye proposed,
      although functional consequences of muscarinic receptor activation are not always
      fully characterized. The present paper reviews current knowledge about the
      presence of muscarinic receptors in the ocular surface and the implication of
      alterations on their expression and/or functioning in eye diseases. RECENT
      FINDINGS: Several authors have described alterations in muscarinic receptor
      subtype expression in the eye under pathological conditions. In conjunctiva of
      vernal keratoconjunctivitis patients, the expression of muscarinic receptor
      subtypes is altered in both the epithelium and stroma. Under proinflammatory
      conditions, M2-muscarinic receptor expression is upregulated in conjunctival
      epithelial cells in vitro. M3-muscarinic receptor altered distribution has been
      found in the lacrimal gland of NOD mice. SUMMARY: The cholinergic muscarinic
      system plays diverse roles. Alteration in the expression and/or functioning of
      muscarinic receptors may be implicated in the etiopathogenesis of some ocular
      diseases. Their pharmacological regulation may therefore have therapeutic value.
      Knowledge of the specific receptor subtypes expressed in each tissue may help to
      avoid some undesired secondary side effects in some cases when muscarinic
      agonists or antagonists are used.

PMID- 16954794
TI  - Pharmacology of ocular allergy.
AB  - PURPOSE OF REVIEW: To evaluate the pharmacology of current drug development
      directed towards ocular allergy. Increased worldwide prevalence of ocular allergy
      has stimulated expansion of management strategies towards physiologic and
      immunologic drug targets. RECENT FINDINGS: Present drug targets are located in
      the conjunctival mucosal surface at the initial site of allergen exposure.
      Pharmacologic intervention attends to early and late phase reactions. Targets
      generating a response include mast cells, IgE, released preformed mediator
      histamine, and newly formed mediators, such as prostaglandins, leukotrienes and
      cytokines. Methods to simulate allergy and measure efficacy of drugs are the
      conjunctival allergen challenge and the conjunctival provocation test.
      Pharmacologic outcome is measured via cytologic biomarkers and clinical
      signs/symptoms of redness, itching, lid swelling and chemosis. Endpoint
      instruments such as the Ocular Allergy Index and Eye Allergy Patient Impact
      Questionnaire have emerged from the field of pharmacoeconomics. SUMMARY:
      Important pharmacologic properties of targets have been revealed. First,
      histamine is more specifically antagonized by second generation antihistamines.
      Second, newly formed mediators and downstream responders (prostaglandins,
      leukotrienes, interleukins, intercellular adhesion molecule 1, tumor necrosis
      factor, vascular cell adhesion molecule, eosinophils and neutrophils) are more
      selectively antagonized by dual/multiple-action agents.

PMID- 16954797
TI  - Pulmonary rehab: opportunity is knocking for RDs.

PMID- 16954798
TI  - What rehabilitation therapists need to know about nutrition and why: nutrition
      education for members of the health care team-part IV.

PMID- 16954800
TI  - Away-from-home foods: final report released by the keystone forum.

PMID- 16954801
TI  - Azathioprine maintains first remission in newly diagnosed pediatric Crohn's
      disease.
AB  - 6-Mercaptopurine (6-MP) maintains remission in pediatric Crohn's disease (CD).
      Azathioprine, a prodrug of 6-MP, is used for maintenance of remission of CD in
      Europe. We evaluated to what extent azathioprine is used in newly diagnosed
      pediatric CD patients and whether maintenance of remission differed between
      patients using azathioprine or not. Charts of children (diagnosed 1998-2003,
      follow-up > or = 18 mo) were reviewed. Active disease was defined as Pediatric
      Crohn's Disease Activity Index (PCDAI) greater than 10 or systemic corticosteroid
      use. Remission was defined as PCDAI 10 or less without use of corticosteroids.
      Eighty-eight children (55M/33F, age 12 +/- 3 yr) were included. Seventy-two (82%)
      patients received azathioprine during the follow-up period (38 +/- 17 mo).
      Patients diagnosed after 2000 received azathioprine significantly earlier during
      the course of disease compared with those diagnosed earlier (median, at 233 vs.
      686 days; P < 0.05). At initial presentation, moderate-severe disease activity
      and prescription of corticosteroids were more prevalent in patients using
      azathioprine compared with nonazathioprine patients (75% vs. 52%; P < 0.05; and
      89% vs. 58%; P < 0.005, respectively). Duration of corticosteroid use was longer
      in patients receiving azathioprine (232 vs. 168 days; P < 0.005). Median
      maintenance of first remission in patients who initially used corticosteroids,
      however, was longer in patients receiving azathioprine compared with
      nonazathioprine patients (PCDAI, 544 vs. 254 days, P = 0.08; corticosteroid free,
      575 vs. 259 days, P < 0.05, respectively). We conclude that, since 2000,
      azathioprine is being introduced earlier in the treatment of newly diagnosed
      pediatric CD patients. The use of azathioprine is associated with prolonged
      maintenance of the first remission.

PMID- 16954802
TI  - Detection of elafin as a candidate biomarker for ulcerative colitis by whole
      genome microarray screening.
AB  - The cause of ulcerative colitis (UC) is largely unknown. Microarray studies are
      an efficient way of investigating the various genes involved. Here, we have used
      whole-genome microarrays to clarify the clinical picture and to identify new
      biomarkers for improved diagnosis. Rectal biopsies were taken from five UC
      patients and five matched controls, and RNA transcripts were prepared. After
      labeling, each sample was individually applied to the microarray chips. All
      transcripts that were more than 10-fold up-regulated in all five patients were
      analyzed further in seven additional patients and seven controls using
      quantitative polymerase chain reaction. Of 47,000 transcripts examined, 4 were
      highly up-regulated in all patients: those encoding elafin, a secreted protease
      inhibitor, the ion and amino acid transporter B (SLC6A14), and the metabolic
      enzyme aldolase B, as well as a recently identified transcript named similar to
      numb-interacting homolog. The up-regulation of these transcripts appears to
      follow the progression of the disease because elevated expression was detected in
      the proximal part of the colon in patients with total colitis but not in patients
      with left-sided colitis. Immunohistologic examination showed very distinct
      differences in the expression of elafin. Extensive expression was detected in
      enterocytes and goblet cells of the affected mucosa, whereas there was no
      detectable expression in unaffected mucosa and in healthy controls. The results
      implicate four transcripts and proteins of special interest as possible targets
      for pharmacologic interference and as biomarkers in UC. Of these, elafin may be
      of special interest because it is a secreted protein that may be measured in body
      fluids.

PMID- 16954803
TI  - Correlation between cyclical epithelial barrier dysfunction and bacterial
      translocation in the relapses of intestinal inflammation.
AB  - BACKGROUND: Although several factors have been implicated in the pathogenesis of
      inflammatory bowel disease (IBD), the mechanisms underlying the recurrent
      relapses have not yet been clarified. We hypothesized that epithelial barrier
      dysfunction, associated with intestinal motor disturbances, could play a key role
      in exacerbation of inflammatory illness due to an increased uptake of luminal
      antigen and bacterial translocation. METHODS: Indomethacin administration to rats
      induced a long-lasting oscillation of active and quiescent phases of inflammation
      associated with phases of hypo and hypermotility. Rats selected at either active
      or quiescent phase and from 2 to 60 days after indomethacin treatment were used.
      Short-circuit current; conductance and HRP flux were evaluated in small
      intestinal segments mounted in Ussing Chambers. Enterocyte endosomes containing
      HRP and ultrastructural damage were assessed by electron microscopy. Bacterial
      translocation was determined by cultures from mesenteric lymph nodes. RESULTS:
      Rats with induced enteritis in both phases demonstrated a long-lasting increase
      of epithelial paracellular permeability. In contrast, transcellular permeability
      was only disturbed during the active phases, coinciding with bacterial
      translocation and the increase in inflammatory parameters. Furthermore, although
      mithochondrial damage was observed throughout the inflammatory state, alterations
      were worse during the active phase. CONCLUSIONS: The sustained enhancement of
      paracellular permeability could facilitate the constant passage of luminal
      antigens through the mucosa, and hence, be the basis for chronicity. By contrast,
      transcellular permeability only increases during the active phases, when
      hypomotility and bacterial translocation are also present, suggesting this factor
      may play a critical role in the course of acute relapses in IBD.

PMID- 16954804
TI  - Host gene expression in the colon of gnotobiotic interleukin-2-deficient mice
      colonized with commensal colitogenic or noncolitogenic bacterial strains: common
      patterns and bacteria strain specific signatures.
AB  - BACKGROUND: Specific pathogen-free (SPF), but not germfree (GF), interleukin (IL)
      2-deficient (IL-2-/-) mice develop inflammatory bowel disease (IBD) at 10 to 15
      weeks of age. Gnotobiotic IL-2-/- mice monocolonized with E. coli mpk develop IBD
      at 25 to 33 weeks of age but not B. vulgatus mpk, E. coli Nissle 1917, or mice
      cocolonized with both E. coli mpk and B. vulgatus. METHODS: To determine genes
      regulated by these commensal bacteria, host gene expression in the colon of 8
      week-old IL-2-/- mice was compared by using microarrays and semiquantitative
      reverse-transcription polymerase chain reaction. Colonization with E. coli mpk/B.
      vulgatus or SPF microbiota altered the gene expression profile more profoundly
      than monocolonization with either B. vulgatus, E. coli mpk or E. coli Nissle
      indicating that the complexity of the gene expression pattern is influenced by
      the diversity of the microbiota. RESULTS: A small but distinct group of genes
      could be defined which might be associated with colitis development. Thus, 8 week
      old E. coli mpk IL-2-/- mice rone to colitis compared to E. coli Nissle, B.
      vulgatus and E. coli mpk/B. vulgatus IL-2-/- mice displayed a lower expression of
      the anti-inflammatory RegIII family genes such as RegIII[gamma] and pancreatitis
      associated protein (PAP) and peroxisome proliferator-activated receptor-[gamma]
      regulated genes such as adipsin and adiponectin. CONCLUSION: The increased
      expression of these genes in B. vulgatus colonized mice might be associated with
      prevention of E. coli mpk triggered colitis in E. coli mpkM/B. vulgatus IL-2-/-
      mice.

PMID- 16954805
TI  - Matrix metalloproteinases as profibrotic factors in terminal ileum in Crohn's
      disease.
AB  - BACKGROUND: Returning stenosis in Crohn's disease (CD) patients is poorly
      understood. After resection, newly developed strictures are seen within 10 years
      in 50% to 70%. Matrix metalloproteinases (MMPs) are involved in matrix-turnover
      processes. This study analyzes spatial expression of MMP-1, MMP-3, MMP-9, tissue
      inhibitor of MMP-1, and collagen III to get better insight in tissue remodeling
      of terminal ileum of CD patients. METHODS: Expressions were analyzed on mRNA and
      the protein level (MMP-1, MMP-3) in segments from resected terminal ileum from CD
      and control patients. In CD, macroscopic distinction was made between proximal
      resection margin, prestenotic, and stenotic tissue. Immunohistochemistry allowed
      for expression analyses transmurally. RESULTS: MMP-1 and MMP-3 gene expression
      was up-regulated (P < 0.05) in both prestenotic and stenotic tissue. MMP-1
      protein was significantly up-regulated in submucosal and muscular tissue of
      prestenotic parts and in muscular tissue of stenotic Crohn samples. MMP-3 protein
      was significantly up-regulated in all layers of prestenotic and stenotic Crohn
      samples. Even in submucosa of proximal resection margin tissue, MMP-3 expression
      was significantly higher than in controls. CONCLUSION: Surprisingly, in proximal
      resection margin tissue up-regulated MMP-3 was seen. This suggests that in
      nonresected terminal ileum, in which anastomosis is made, tissue turnover is
      present, which may account for the high recurrence of intestinal strictures.

PMID- 16954806
TI  - The role of vascular endothelial growth factor (VEGF) in inflammatory bowel
      disease.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a candidate
      susceptibility gene to inflammatory bowel disease (IBD), both from a functional
      as well as genetic perspective. Moreover, serum VEGF (sVEGF) levels are increased
      in IBD and correlate with disease activity. Both VEGF expression and sVEGF levels
      may be influenced by VEGF gene polymorphisms. AIMS: To study VEGF polymorphisms
      in IBD susceptibility and their impact on sVEGF levels. METHODS: Four functional
      VEGF polymorphisms (-C2578A, -G1154A, -G634C, and C936T) were genotyped in two
      independent cohorts (cohort 1: 372 IBD trios; cohort 2: 452 unrelated IBD
      patients, 271 healthy controls [HC]; and 93 patients with non-IBD
      gastrointestinal inflammation [non-IBD GI]), using polymerase chain reaction with
      restriction fragment length polymorphism and TaqMan minor groove binding.
      Phenotypical data on all patients as well as sVEGF levels were correlated with
      the genetic data. RESULTS: Both the VEGF genotype and haplotype frequencies did
      not differ between IBD patients and controls, and no distortion of transmission
      was observed. sVEGF levels were increased in IBD but also in non-IBD GI patients,
      compared with HC, and were only influenced by VEGF polymorphisms in patients with
      Crohn's disease (-G1154A genotype and -2578/-1154/-634 AAG promoter haplotype).
      CONCLUSIONS: The VEGF polymorphisms studied are not implicated in susceptibility
      to IBD and do not predict sVEGF levels. Although increased sVEGF and angiogenesis
      are important features of IBD, they do not appear genetically determined.

PMID- 16954807
TI  - Frequent detection of cytomegalovirus in the intestine of patients with
      inflammatory bowel disease.
AB  - BACKGROUND: Although a growing number of reports have described inflammatory
      bowel disease (IBD) complicated with cytomegalovirus (CMV) infection, there are
      limited molecular studies that investigate CMV genome in intestinal sections of
      patients with IBD. METHODS: A cross-sectional prospective study was conducted
      between September 2000 and June 2003 in a cohort of 85 patients diagnosed with
      IBD (58 with ulcerative colitis and 27 with Crohn's disease) in two adult
      gastrointestinal referral centers in Athens, Greece. Prevalence of CMV infection
      was estimated by pathologic studies in intestinal sections and by molecular
      assays in blood and intestinal tissue samples and compared with a control group
      of 42 individuals with noninflammatory disease. RESULTS: Immunohistochemical
      staining showed CMV antigen in 10 IBD patients (7 with ulcerative colitis; 9 with
      severe disease), whereas CMV antigen was not detected in any of the controls. CMV
      genome in both the intestinal tissue and blood was found by polymerase chain
      reaction in 23 (27.1%) of the total IBD patients, in 18 (31.0%) of those with
      ulcerative colitis, and in 5 (18.5%) of those with Crohn's disease. In addition,
      five (5.9%) IBD patients (2 with ulcerative colitis and 3 with Crohn's disease)
      had detectable CMV genome in their intestinal samples but not in their blood. In
      the control group, five (11.9%) individuals had detectable CMV genome in their
      blood, but only one (2.2%) in his intestine. CONCLUSION: Patients with ulcerative
      colitis had more often detectable CMV genome in their blood as well as in their
      intestinal tissue samples as compared with controls (P = 0.022 and P < 0.0001,
      respectively). However, patients with Crohn's disease had more often detectable
      CMV genome only in their intestinal tissue samples as compared with controls (P =
      0.001). Detection of CMV genome in blood or intestinal tissue was significantly
      associated with short duration of IBD (P = 0.0088 and 0.04, respectively) but not
      with age, sex, severity of the disease, activity at colonoscopy, pancolitis,
      administration of a specific treatment, and surgery. In this cross-sectional
      prospective study, detection of CMV genome or antigen in the intestine was
      commonly associated with IBD.

PMID- 16954808
TI  - Challenges in pediatric inflammatory bowel disease.
AB  - It is estimated that of the >1 million individuals in the United States with
      inflammatory bowel disease (IBD), approximately 100,000 are children. IBD that
      begins in childhood affects the individual at a critical period of growth and
      development. Children with Crohn's disease and ulcerative colitis may experience
      complications such as growth failure, school absence, and depression. In
      addition, because children with IBD have fewer environmental confounders such as
      smoking, children may be an excellent population to study microbial and immune
      interactions. Despite these opportunities, the discipline of pediatric IBD
      investigation is still in its infancy. In September of 2005, a group of
      investigators with expertise in pediatric IBD met in Boston (Massachusetts) to
      review the current status of childhood IBD research and to develop research
      priorities that warranted funding from the Crohn's and Colitis Foundation of
      America. The group included pediatricians, internists, basic scientists, clinical
      investigators, and members of the administrative staff and board of the Crohn's
      and Colitis Foundation of America. The research needs in respective areas were
      outlined by the heads of 10 focus groups, each with expertise in their respective
      fields (genetics, psychosocial issues, epidemiology, microbiology, immunology,
      quality improvement, pharmacogenomics, nutrition, growth and skeletal health, and
      clinical trials). Before the conference, heads of the research focus groups
      developed their proposals with experts in the field. At the end of the
      conference, members of the focus groups and members of the steering committee
      rated the proposed areas of study in terms of feasibility and importance. It was
      recommended that the Crohn's and Colitis Foundation of America focus its initial
      efforts in pediatric IBD in 5 areas: the effects of inflammation on growth and
      skeletal development, the genetics of early-onset IBD, the development of quality
      improvement interventions to standardize and improve clinical care of children
      with IBD, the immunology of childhood IBD, and the diagnosis and treatment of
      psychosocial sequelae of childhood IBD. At the conclusion of the meeting,
      investigators discussed the formation of a multicenter collaborative network to
      advance clinical and basic research in the field.

PMID- 16954809
TI  - Polypectomy versus proctocolectomy for adenoma patients with long-standing
      ulcerative colitis.

PMID- 16954810
TI  - Ulcerative colitis patients with dysplastic polyps should be advised to undergo
      colectomy.

PMID- 16954811
TI  - Polypoid dysplasia in inflammatory bowel disease: removing the bumps in the road.

PMID- 16954812
TI  - Steroid dependent ulcerative colitis: azathioprine use is finally "evidence
      based".

PMID- 16954813
TI  - Are COX-2 inhibitors safe for anyone.

PMID- 16954814
TI  - Resveratrol inhibits aggregation of platelets from high-risk cardiac patients
      with aspirin resistance.
AB  - Up to 20% of serious vascular events in high-risk vascular patients is
      attributable to a failure of aspirin (ASA) to suppress platelet aggregation.
      Resveratrol is a cardioprotective phytoestrogen that can inhibit platelet
      aggregation in animal models. We hypothesized that resveratrol can also inhibit
      aggregation of platelets from ASA-resistant (ASA-R) patients. Thus, platelet-rich
      plasma was isolated from ASA-sensitive (ASA-S) and ASA-R patients (aspirin
      resistance was defined as higher-than-expected aggregation to collagen and
      epinephrine [>/=40%] after oral treatment with 100 mg/d ASA). Aggregation to
      adenosine diphosphate (ADP; 5 and 10 mumol/L), collagen (2 mug/mL), and
      epinephrine (10 mumol/L) in the absence and presence of resveratrol (10 mol/L)
      was measured by optical aggregometry. Maximal aggregation to 5 mumol/L ADP was
      only slightly affected by resveratrol. Similar results were obtained using 10
      mumol/L ADP. Maximal aggregation of ASA-R platelets to collagen was significantly
      decreased by resveratrol, whereas resveratrol had only marginal effects in ASA-S
      platelets. Similar results were obtained with epinephrine as well. Collectively,
      resveratrol effectively inhibited collagen- and epinephrine-induced aggregation
      of platelets from ASA-R patients, which may contribute to its cardioprotective
      effects in high-risk cardiac patients.

PMID- 16954815
TI  - Synthetic oligosaccharide stimulates and stabilizes angiogenesis: structure
      function relationships and potential mechanisms.
AB  - To determine the proangiogenesis effect of series of saccharides and a synthetic
      oligosaccharide and potential mechanisms, an in vitro 3-dimensional endothelial
      cell sprouting (3D-ECS) assay and the chick chorioallantoic membrane (CAM) model
      were used. We demonstrated that a sulfated oligosaccharide significantly promotes
      the endothelial capillary network initiated by vascular endothelial growth factor
      (VEGF) and basic fibroblast growth factor (b-FGF). Furthermore, although the
      capillary network initiated by VEGF and b-FGF lasts no more than 7 days, addition
      of a sulfated oligosaccharide significantly amplifies angiogenesis and stabilizes
      the capillary network of new blood vessels. In the CAM model, sulfated
      oligosaccharide also stimulated angiogenesis. In both the CAM and the 3D-ECS
      assay, structure-function studies reveal that increased saccharide chain length
      up to the hexa- to decasaccharide show optimal proangiogenesis efficacy. In
      addition, the sulfation and molecular shape (branched vs linear) of
      oligosaccharide are important for sustained proangiogenesis efficacy. Data
      indicate that chemically defined synthetic oligosaccharides can play an important
      role in regulation of capillary structure and stability, which may contribute to
      future advances in therapeutic angiogenesis. The proangiogenesis efficacy of an
      oligosaccharide is mediated via integrin alphavbeta3 and involves mitogen
      activated protein kinase signaling mechanisms.

PMID- 16954816
TI  - Sanguinarine downregulates AT1a gene expression in a hypertensive rat model.
AB  - We studied the in vivo effects of sanguinarine in a hypertensive rat model and
      its effects on AT1a mRNA expression in kidney tissues. Rats received daily for 14
      d sanguinarine 0.1 mg/kg (SangL) and 0.3 mg/kg (SangH), losartan 1 mg/kg by
      weight (Los), or DMSO (Con). Blood pressures were monitored regularly and urine
      volume and sodium concentration was measured on days 0, 7, and 14. On day 15,
      animals were anesthetized (sodium thiopentane, 50 mg/kg), blood samples for
      aldosterone levels were taken, and kidneys were removed for AT1a mRNA expression.
      Los and SangH groups showed reduced AT1a mRNA expressions by 4.22- and 5.9-fold,
      respectively. In the SangL group it was reduced by 2.7-fold. Decreases in
      systolic blood pressures mirrored decreases in AT1a mRNA expressions in all
      groups. Los and SangH groups showed reductions in systolic blood pressure of
      12.3% and 19.3%, respectively, whereas in the SangL group, it was reduced by
      8.07%. Urine output in the Los group increased (228% mean increase from days 0
      14), whereas sodium excretion decreased by 69.6% (mean decrease from days 0-14).
      In the SangL and SangH groups, urine volumes increased significantly by 108.3%
      and 115% (mean increase from days 0-14), respectively. Urinary sodium excretion
      increased significantly by 60.9% in the SangH group. We concluded that
      sanguinarine reduces blood pressure in the Dahl rat because of decreased AT1
      receptor expression and reduced aldosterone levels. The action of losartan on
      increased urinary volume and decreased sodium excretion may be attributed to
      reduced vasopressin secretion.

PMID- 16954818
TI  - Early aging and anatomic heterogeneity determine cyclooxygenase-mediated
      vasoconstriction to angiotensin II in mice.
AB  - We previously reported that angiotensin II (AngII)-induced vasoconstriction
      involves activation of cyclooxygenase (COX) in murine aorta and carotid artery.
      The aim of this study was to investigate the roles of early aging and COX in
      AngII-induced vasoconstriction in different vascular beds. Aortic, carotid,
      renal, and femoral artery rings of 19- and 34-week-old C57BL/6 mice were
      pretreated with the nitric oxide synthase inhibitor L-NAME (300 micromol/L) to
      exclude effects of NO. Contractions to AngII (100 nmol/L) were recorded in the
      presence or absence of meclofenamate (10 micromol/L), a nonselective COX
      inhibitor. The results indicate a pronounced heterogeneity in the vascular
      responsiveness to AngII. Renal and femoral artery rings showed stronger
      contractions than aorta or carotid artery (P < 0.01 for both). In all vessels of
      young animals COX inhibition with meclofenamate only partially blocked
      vasoconstriction to AngII, whereas contractions were completely abolished in the
      aorta and carotid artery of older mice (P < 0.05 vs untreated for both). These
      data demonstrate that COX determines AngII-induced vasoconstriction in the mouse
      aorta and carotid artery during the early physiological aging process,
      independent of endothelial NO bioactivity. AngII-induced vasoconstriction in
      vessels more distal to the heart such as femoral and renal arteries is only in
      part mediated by COX-dependent mechanisms that remain unaffected by early aging.

PMID- 16954817
TI  - Suppression of calcium-induced repolarization heterogeneity as a mechanism of
      nitroglycerin's antiarrhythmic action.
AB  - This study examined whether the antifibrillatory action of nitroglycerin (NTG) is
      attributable to reduction in calcium-induced heterogeneity of repolarization
      independent of autonomic and coronary vasodilatory influences. The effects of
      intrapericardial (IPC) NTG on coronary blood flow, contractility, repolarization,
      and arrhythmia susceptibility were measured in anesthetized pigs (N = 43).
      Autonomic influences were minimized by vagotomy and beta-adrenergic blockade
      (metoprolol, 1.25 mg/kg, intravenous). Electrophysiological parameters were
      tested at 30 min, a time when coronary hemodynamics had returned to baseline.
      Intracoronary calcium chloride (CaCl2, 50-mg bolus) injection augmented
      contractility (dP/dt(max), 1760 +/- 144 to 2769 +/- 274 mmHg/s, and following
      NTG, 1531 +/- 384 to 2138 +/- 242 mmHg/s, P < 0.0002), reflecting increased
      myocardial intracellular calcium. Calcium increased repolarization heterogeneity
      (interlead precordial T-wave heterogeneity, 95 +/- 15 to 264 +/- 33 microV, P <
      0.006; T(peak)-T(end), an index of transmural dispersion of repolarization, 37 +/
      3 to 76 +/- 6 ms, P < 0.05) and lowered repetitive extrasystole threshold (RET;
      24 +/- 2 to 13 +/- 1 mA, and following NTG, 32 +/- 4 to 18 +/- 1 mA, P < 0.0001).
      IPC NTG raised the RET from baseline by 33% and blunted calcium-induced
      contractility (dP/dt(max) by 23%, P < 0.05), repolarization changes (T-wave
      heterogeneity by 24%, P < 0.006; T(peak)-T(end) by 18%, P = 0.04), and arrhythmia
      vulnerability (RET by 39%, P < 0.003). Thus, the capacity of NTG to suppress
      calcium-induced repolarization heterogeneity is an important mechanism of its
      antiarrhythmic action, which is independent of autonomic and vasodilatory
      actions.

PMID- 16954819
TI  - Inhibition of human pulmonary artery smooth muscle cell proliferation and
      migration by sabiporide, a new specific NHE-1 inhibitor.
AB  - Abnormal growth of vascular smooth muscle cells is seen in various pathological
      conditions such as hypertension, atherosclerosis, and restenosis. Na/H exchanger
      (NHE) activation appears to play a permissive role in vascular smooth muscle cell
      proliferation and vascular remodeling. The present study investigated the effect
      of a new specific NHE-1 inhibitor, sabiporide, on human pulmonary artery smooth
      muscle cell proliferation and migration. Concentrations of sabiporide as low as
      20 micromol/L in the culture medium containing growth factors inhibited cell
      proliferation, as measured by cell counting, and also inhibited the rate of DNA
      synthesis, as examined by measuring BrdU incorporation into DNA. Cell growth
      inhibition was not caused by cell death, as demonstrated by the measurement of
      intracellular lactate dehydrogenase release and by the reversibility of
      inhibition upon washing. By fluorescent-activated cell sorting analysis, we are
      the first to demonstrate that NHE-1 inhibition arrests the cell cycle progression
      at G0/G1 phase, suggesting that NHE activation plays a permissive role in
      entrance of cells into the cell cycle. Sabiporide also concentration-dependently
      inhibited human pulmonary artery smooth muscle cell migration. The present study
      showed that sabiporide inhibits vascular smooth muscle cell proliferation and
      migration by blocking the cell cycle progression at G0/G1 phase.

PMID- 16954820
TI  - Salusins protect neonatal rat cardiomyocytes from serum deprivation-induced cell
      death through upregulation of GRP78.
AB  - Salusin-alpha and salusin-beta are newly identified bioactive peptides with
      hemodynamic and mitogenic activities. Recent studies have shown that salusins
      improve calcium uptake and protein synthesis in neonatal rat cardiomyocytes,
      suggesting that salusins may be regulatory factors for myocardial growth and
      hypertrophy. In this study, we investigated whether salusins improve the survival
      of cardiomyocytes after serum deprivation. Cultured neonatal cardiomyocytes were
      treated with or without salusins (salusin-alpha or salusin-beta) at a
      concentration range of 10 to 10 mol/L for 24 h under serum deprivation
      conditions. Cardiomyocytes viability was determined by 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyl tetrazonium bromide assay. Cell death or apoptosis rate was
      identified by flow cytometry analysis. Compared to serum deprivation-only groups,
      cardiomyocyte viability was significantly increased in salusin-alpha or salusin
      beta groups. Cell death rate was decreased after administration of 10 mol/L
      salusin-alpha or salusin-beta. Salusin-beta was able to decrease the apoptotic
      rate. Salusins also increased the expression of cardiomyocyte glucose-regulated
      protein 78 (GRP78) as estimated by Western blot. Furthermore, antisense
      oligodeoxynucleotide specifically against GRP78 attenuated or abrogated
      antiapoptosis or survival effects of salusin-beta. These findings suggest that
      salusin-alpha and salusin-beta may be a potential survival factor against serum
      deprivation-induced myocardial cell death and that this cardioprotective effect
      may involve an upregulation of GRP78 expression in cardiomyocytes.

PMID- 16954821
TI  - Selective inhibition by grape seed proanthocyanidin extracts of cell adhesion
      molecule expression induced by advanced glycation end products in endothelial
      cells.
AB  - The interaction of advanced glycation end products (AGE) with their cell surface
      receptors for AGEs (RAGE) has been causally implicated in the pathogenesis of
      diabetic vascular complications and has been shown to stimulate cell adhesion
      molecule expression in endothelial cells via induction of reactive oxygen species
      (ROS). Alternatively, grape seed proanthocyanidin extracts (GSPE), which are
      naturally occurring polyphenolic compounds, have been reported to possess potent
      radical scavenging and antioxidant properties and to display significant
      cardiovascular protective action. In this study, we investigated whether GSPE
      could inhibit AGE-induced cell adhesion molecule expression through interference
      with ROS generations in human umbilical vein endothelial cells. AGE-modified
      bovine serum albumin (AGE-BSA) was prepared by incubating BSA with a high
      concentration of glucose. Stimulation of cultured human umbilical vein
      endothelial cells with 200 microg/mL of AGE-BSA significantly enhanced
      intracellular ROS formation and subsequently upregulated the expression of
      vascular cell adhesion molecule-1 (VCAM) and intercellular adhesion molecule-1
      (ICAM-1), whereas both unmodified BSA and GSPE alone were without effect.
      However, preincubation of different concentrations of GSPE markedly downregulated
      AGE-BSA-induced VCAM-1 expression at the surface protein and mRNA level in a
      concentration-dependent manner, but the increased ICAM-1 expression was not
      affected by GSPE treatment. Meanwhile, the inhibition by GSPE of intracellular
      ROS generation was also observed at defined time periods. These results
      demonstrate that GSPE can inhibit the enhanced VCAM-1 expression but not ICAM-1
      in AGE-exposed endothelial cells by suppressing ROS generation. Hence, GSPE may
      have therapeutic potential in the prevention and treatment of vascular
      complications in patients with diabetes.

PMID- 16954822
TI  - Inhibitory effects of procyanidin B(2) dimer on lipid-laden macrophage formation.
AB  - A proteomic analysis of procyanidin B(2) isolated from cocoa against oxidized low
      density lipoprotein-induced lipid-laden macrophage formation was performed. Of
      approximately 400 detected proteins, 12 were differentially expressed as a result
      of B(2) treatment. They were subsequently identified by liquid chromatography
      electrospray ionization-tandem mass spectrometry and the SWISS-PROT database.
      Further reverse transcriptase-polymerase chain reaction and Western blot analysis
      revealed that B(2) strongly inhibited arachidonic acid inflammatory reactions,
      apoptosis, and their coupled mitogen-activated protein kinase and NF-kappaB
      pathways. To highlight proteins or genes with similar expressed patterns and
      similarly biological function induced by B(2) in lipid-laden macrophages, a
      cluster and Kyoto Encyclopedia of Genes and Genomes pathway analysis were
      performed. The data were mapped to multiple pathways. Further validation of the
      bioinformatic results revealed that activation of Wnt signaling may contribute to
      the cardioprotection of B(2). The differentially expressed genes and proteins
      mentioned above induced by B(2) are through regulating nuclear transcription
      factors, activating peroxisome proliferator-activated receptor-gamma and
      inhibiting AP-1 mRNA expressions. These in vitro data help to interpret the
      beneficial effects of B(2) in reducing the risk of atherosclerosis after
      consumption of flavonoid-rich foods. Many differentially expressed genes induced
      by B(2) help to uncover novel targets and may help to target disease interactions
      in atherosclerosis in the future.

PMID- 16954823
TI  - Abstracts of the 8th World Congress of the Organization for Esophagus Diseases
      (OESO), September 3-6, 2006.

PMID- 16954916
TI  - Association, commissural, and projection pathways and their functional deficit
      reported in literature.
AB  - This study demonstrates normal white matter structures of the supratentorial
      system revealed by diffusion tensor imaging. Their anatomic connections and
      functional significance are discussed in the context of the lesion-induced
      deficits reported in the literature, which may not fully represent the lesion
      induced effects on the white matter function and may not be entirely specific to
      the tract discussed. Nevertheless, understanding the most common effects of
      lesions on the functional connectivity provides a framework that we can use in
      advanced neuroimaging studies, like diffusion tensor imaging, functional magnetic
      resonance imaging, and positron emission tomography, and in our daily clinical
      practice.

PMID- 16954917
TI  - Preoperative MDCT evaluation of the artery of Adamkiewicz and its origin.
AB  - OBJECTIVE: To assess the usefulness of MDCT in the preoperative evaluation of the
      artery of Adamkiewicz (ARM) and its parent artery. METHODS: Ten patients with
      thoracoabdominal vascular diseases underwent MDCT of the entire aorta and iliac
      arteries. The visualization of the ARM, and its branching level and site of
      origin, and the continuity of the intercostal/lumbar arteries with the ARM were
      investigated. RESULTS: In 9 of the 10 patients, the ARM was clearly visualized.
      The entire length from the intercostal/lumbar arteries to the ARM could be traced
      in 8 of the 10 patients. Surgical treatment or stentgraft insertion was based on
      a consideration of the vascular supply to the ARM. No postoperative ischemic
      spinal complications occurred. CONCLUSIONS: MDCT permits the evaluation of the
      ARM for its entire length and provides information on the intercostal and lumbar
      arteries and entire aorta.

PMID- 16954918
TI  - Comparison between contrast-enhanced magnetic resonance imaging and technetium
      99m glucohepatonic acid single photon emission computed tomography with
      histopathologic correlation in gliomas.
AB  - OBJECTIVE: : To determine and compare the accuracy of contrast-enhanced magnetic
      resonance imaging (MRI) and Technetium 99m glucohepatonic acid single photon
      emission computed tomography (Tc-GHA SPECT) in grading of gliomas, compared with
      neuropathologic findings. MATERIALS AND METHODS: : The study included 20 adult
      patients (13 men and 7 women) with clinical/radiological suspicion of brain tumor
      (glial tumor) who were subjected to magnetic resonance examination and Tc-GHA
      brain SPECT.The lesions were evaluated by using MRI imaging score, based on 9 MRI
      criteria. Based on the discrimination threshold of 0.9 for mean MRI score, the
      gliomas were graded as low- or high-grade glioma. The Tc-GHA SPECT retention
      index was calculated as the ratio between delayed and early uptake ratios. Based
      on the discrimination threshold of 1 for Tc-GHA SPECT retention index, the
      gliomas were graded as low- or high-grade glioma.The diagnosis was verified by
      means of histopathologic examination in all patients (open surgery in 19 patients
      and stereotactic biopsy in 1 patient). Correlation between MRI findings/scores,
      SPECT scores, and histopathologic grades was done in all the patients, and
      comparison between MRI and Tc-GHA SPECT was made using paired Student t test and
      correlation coefficient. RESULTS: : The study revealed significant difference
      between the mean MRI scores and early uptake ratio, delayed uptake ratio, and
      retention index of low-grade (grades I-II) and high-grade (grades III-IV)
      gliomas. No statistically significant difference could be demonstrated between
      the abilities of contrast-enhanced MRI and Tc-GHA SPECT to allow differentiation
      between high- and low-grade gliomas. The accuracy of MRI (78.4%), however, was
      slightly higher than that of Tc-GHA SPECT (73.68%). However, Tc-GHA SPECT allowed
      differentiation between high-grade gliomas (between grades III and IV gliomas).
      CONCLUSIONS: : The accuracy of contrast-enhanced MRI in the distinction of high-
      and low-grade malignancy was higher than that of Tc-GHA SPECT. The performance of
      Tc-GHA SPECT adds little in determining tumor grade when MRI is performed.
      However, it may act as a useful adjunct to differentiate between grades III and
      IV gliomas.

PMID- 16954919
TI  - The effect of skull volume and density on differentiating gray and white matter
      on routine computed tomography scans of the head.
AB  - Increased volume and density of the skull makes computed tomography
      differentiation of gray and white matter (GM and WM, respectively) more
      difficult. The purpose of this investigation was to study the effects of skull
      volume and bone density on GM and WM differentiation. A total of 21 patients with
      thick skulls and 22 controls were included in this study. Three consecutive
      slices from the computed tomography scan were analyzed. The basal ganglia had to
      be visualized on at least 1 slice. Calvarial volume measurement, mean pixel value
      in each slice, and Hounsfield unit difference between WM and GM, were compared
      between the thick-skulled and control groups. The mean bone volume of each slice
      in the thick-skulled group was 55.7, 54.3, and 56 mL, whereas the mean volume of
      each slice in the normal group was 39.3, 38.5, and 39.9 mL (P < 0.001). In our
      series, patients with thick skulls had 41% more bone volume than the normal
      group. The mean skull pixel value in each slice was 935.9 in patients with thick
      skulls and 987 in patients in the normal group. There was no difference between
      right and left sides of the same group of patients. Patients with larger volumes
      of skull have significant decrease in the Hounsfield unit of the GM and WM
      compared with the control group. As a result, diagnosing any low-contrast brain
      abnormality including early/subtle infarction in subjects with a thicker
      calvarium may be more difficult.

PMID- 16954920
TI  - Angiographic computed tomography is comparable to multislice computed tomography
      in lumbar myelographic imaging.
AB  - We evaluated the feasibility of angiographic computed tomography (ACT) for
      diagnostic imaging in a patient with degenerative lumbar spine disease. ACT
      provides a volume data set out of a rotational acquisition with a c-arm-mounted
      flat-panel detector. Using this technique, radiographic myelography and
      myelographic computed tomography can be performed in a single session at the same
      imaging system. The quality of the reconstructed ACT slice images is comparable
      to those acquired by postmyelographic computed tomography.

PMID- 16954921
TI  - Serial diffusion-weighted magnetic resonance imaging in methanol intoxication.
AB  - We report the serial magnetic resonance imaging (MRI) findings in a case of
      methanol intoxication. A 50-year-old man who had accidentally ingested methanol
      was admitted to our institution. The patient was almost blind, and became
      comatose. The MRI showed bilateral putaminal lesions with restricted diffusion.
      The MRI, which was performed on the third day after admission, showed new lesions
      in the subcortical white matter. The patient's general condition improved. His
      visual acuity, however, did not improve.

PMID- 16954922
TI  - CT and MR imaging evaluation of hepatic adenoma.
AB  - Hepatic adenoma is a rare benign epithelial tumor that is usually encountered in
      young women who use oral contraceptives. It is clinically significant because of
      the risk of hemorrhage and of its low-grade malignancy potential. Adenomas
      usually are mildly hypervascular at contrast-enhanced CT and MR imaging, and
      heterogeneous due to the presence of hemorrhage, necrosis, calcifications and
      fat. The objective of our study was to illustrate the CT and MR imaging findings
      of hepatic adenoma.

PMID- 16954923
TI  - Improved visualization of the urinary tract in multidetector CT urography
      (MDCTU): analysis of individual acquisition delay and opacification using
      furosemide and low-dose test images.
AB  - PURPOSE: To retrospectively analyze the reliability of opacification and image
      quality of a modified MDCTU examination protocol using furosemide and an
      individual acquisition delay by low-dose test images MATERIALS AND METHODS:
      Excretory phase images obtained from 4-row and 16-row MSCTU examinations in 103
      patients (69 men, 34 women) were independently reviewed by two radiologists.
      MDCTUs were performed by using a low-dose furosemide iv injection. No fixed delay
      for urographic image acquisition was applied. Urographic timing was individually
      adjusted by performing low-dose test images of the distal ureters to display
      their current opacification. Image analysis included grading of opacification and
      image quality of the segmented collecting system. Average urographic delay was
      calculated. Stratified comparisons of mean scores were assessed. Interobserver
      kappa values were calculated. RESULTS: Calculated median scan delay for patients
      with normal creatine levels (n = 92) was 420 sec (mean 453 sec; SD, 121 sec). The
      median number of acquired test images was 2 (range 1-6 images). The analysis of
      opacification demonstrated that 97% of the ICS, 89% of the proximal, 86% of the
      middle, and 81% of the distal ureter segments showed opacification greater than
      90%. 7.8% of the distal ureteral segments could not be visualized. Statistics did
      not show significant differences of opacification between proximal, middle, and
      distal ureteral segments (P > 0.05). Overall image quality of MSCTU showed to be
      high when latest test images indicated homogeneous bilateral contrasted ureters
      (Pearson correlation coefficient r= 0.81). Interobserver kappa values were 0.8
      and 0.78. CONCLUSION: Furosemide and scan delay timing by means of test images
      for MDCTU proved to be a reliable procedure to reach improved opacification of
      the upper urinary tract. It features the individual adaption of MDCTU to the
      excretory rate of the kidneys.

PMID- 16954924
TI  - Multidetector computed tomography for suspected appendicitis: multi-institutional
      survey of 16-MDCT data acquisition protocols and review of pertinent literature.
AB  - PURPOSE: To determine acquisition protocol parameters currently used by different
      institutions for appendiceal multidetector computed tomography (MDCT). MATERIALS
      AND METHODS: A survey inquiring about multiple MDCT protocols was mailed to 99
      fellows of the Society of Computed Body Tomography in August of 2004, with a
      second mailing sent in May 2005. A total of 46 institutions or hospitals are
      represented by these Society of Computed Body Tomography fellows. Details
      pertaining to protocols for the most advanced MDCT scanner in the department were
      requested. RESULTS: The overall survey response rate was 17 of 46 or 37%. Fifteen
      protocols using 16-MDCT for suspected appendicitis were collected and tabulated.
      Parameters that are similar across institutions include a nonfocused acquisition
      using oral and intravenous contrast. Detector configuration is even divided
      between submillimeter and greater than 1 mm, and the most common reconstruction
      section thickness is 5 mm. CONCLUSIONS: Contrast administration and anatomical
      coverage are quite consistent across this set of protocols. However, future
      appendiceal MDCT research will need to address the most efficacious detector row
      collimation, reconstruction section thickness and interval, and the diagnostic
      capacity of protocols implementing dose reduction measures.

PMID- 16954925
TI  - Newly developed hepatocellular carcinoma (HCC) in chronic liver disease: MR
      imaging findings before the diagnosis of HCC.
AB  - PURPOSE: The purpose of this work was to describe the initial magnetic resonance
      (MR) imaging findings obtained before an imaging diagnosis of overt
      hepatocellular carcinoma (HCC) in the chronically damaged liver. METHODS: One
      hundred fifty-two newly diagnosed HCCs diagnosed by dynamic computed tomography
      (n = 111) or by MR imaging (n = 41), in addition to digital subtraction hepatic
      arteriography, in 96 patients were subjected to analysis of their MR imaging
      features within the previous 2 years. RESULTS: Ninety-seven (64%) HCC cases
      showed no focal lesions distinguishable from background hepatic parenchyma in MR
      images taken before the indication of typical HCC. The remaining 55 (36%) lesions
      were readily identified in earlier images and were categorized into 3 groups:
      nonhypervascular lesions (category I, n = 6), lesions with partially
      hypervascular foci of "nodule-within-nodule" appearance (category II, n = 12),
      and homogeneously hypervascular and/or T2-weighted hyperintense lesions (category
      III, n = 37). The size and doubling time of category III lesions (0.7 cm, 154
      days) were smaller and shorter than those of the other lesions (1.2 cm, 377
      days). CONCLUSIONS: Before the imaging diagnosis of HCCs, the premalignant or
      early malignant lesions can be found on the prior MR images just in the minority
      of the lesions in the cirrhotic liver.

PMID- 16954927
TI  - Automated quantification of body fat distribution on volumetric computed
      tomography.
AB  - OBJECTIVE: To develop a computerized method to automatically quantify visceral
      and subcutaneous fat distribution within the abdomen and pelvis on volumetric
      computed tomographic (CT) images. METHODS: Given the slices of interest, the
      algorithm automatically delineates a contour that separates the visceral fat from
      the subcutaneous fat on each slice. Explicitly, starting with extraction of the
      body perimeter, radii at a fixed angle increment are drawn from the perimeter to
      the center of the body. Along each radius, intensity profile is analyzed to
      determine the point on the subcutaneous fat layer that is closest to the body
      center (inner point). All inner points are then connected to form an inner
      contour, and a specific smoothing algorithm is subsequently applied to correct
      suboptimal results. Pixels having HU values between -190 and -30 are considered
      fat pixels. This procedure is repeated on each of the slices of interest. The
      visceral and subcutaneous fat volumes computed automatically were compared with
      those after the radiologist's adjustments. Ratios of volumetric visceral fat-to
      total fat and visceral fat-to-subcutaneous fat were compared on average and with
      single-slice measurements obtained at L4 and L5 vertebral body levels. RESULTS:
      Subcutaneous and visceral fat were automatically segmented using this algorithm
      on 419 axial CT slices in 9 CT scans (patients) within the abdomen and pelvis.
      The overall average percentage difference between the automated segmentation and
      the segmentation edited by the radiologist were 1.54% for the visceral fat and
      0.65% for the subcutaneous fat. CONCLUSIONS: Preliminary results have shown that
      total compartmental fat, including visceral and subcutaneous fat, can be
      automatically and accurately segmented on volumetric CT.

PMID- 16954926
TI  - Ascending retrocecal appendicitis: clinical and computed tomographic findings.
AB  - OBJECTIVE: To describe the clinical presentation and computed tomographic (CT)
      features of ascending retrocecal appendicitis. METHODS: During the past 8 years,
      1670 patients with surgically proven appendicitis were identified by a
      retrospective investigation. Thirty-three patients who underwent contrast
      enhanced abdominal CT before surgery and had ascending retrocecal appendicitis at
      surgery were included in the patient cohort. The clinical and CT findings of
      these 33 patients were analyzed. RESULTS: Patients presented with right lower
      abdominal pain (49%, 16/33), right flank pain (24%, 8/33), right upper abdominal
      pain (18%, 6/33), and periumbilical pain (15%, 5/33). Inflamed ascending
      retrocecal appendices were visualized completely in 70% (23/33), partially in 21%
      (7 of 33), and not detected in the remaining 9% (3/33). Periappendiceal
      inflammatory changes were most commonly observed in the retrocolic space in 88%
      (29/33), followed by paracolic gutter (30%, 10/33), pararenal space (27%, 9/33),
      mesentery (24%, 8/33), perirenal space (18%, 6/33), and subhepatic space (3%,
      1/33). Inflammatory thickening of Gerota fascia (70%, 23/33) and the lateroconal
      fascia (64%, 21/33) was observed as well. Perforation of the appendix with the
      formation of an abscess was present in 49% (16/33). The abscesses were most
      commonly located in the retrocolic space (88%, 14/16). Diffuse wall thickenings
      of the cecum (67%, 22/33) and the ascending colon (64%, 21/33) were often
      observed also. Appendicoliths were found in 33% (11/33). CONCLUSIONS: More than
      half of patients with ascending retrocecal appendicitis presented with atypical
      clinical presentation. At CT, ascending retrocecal appendicitis was associated
      with a high incidence of retroperitoneal inflammatory changes and appendiceal
      perforation.

PMID- 16954928
TI  - Computed tomography appearance of the Lapra-Ty and Weck hem-o-lok clips in
      patients who recently underwent laparoscopic urologic surgery.
AB  - The nonmetal suture securing Lapra-Ty clip (LTC) and vessel ligating Weck hem-o
      lock clip (WKHL) are useful tools for the laparoscopic surgeon. We report the
      postoperative computed tomography (CT) scan appearance of these clips. The CT
      imaging of patients who underwent urologic surgery demonstrate the WKHL and LTC
      to be radiopaque. Urologists and radiologists should be aware of the radiographic
      appearance of the LTC and WKHL given the ease with which they could be confused
      with urinary lithiasis when applied near the urinary system.

PMID- 16954929
TI  - Signal flare phenomenon as active bleeding in retroperitoneal hematoma with
      hematocrit effect on dynamic CT scan: three clinical cases and experimental study
      based on a specific gravity theory.
AB  - The contrast medium was observed as a thin line indicating active bleeding in the
      cellular component and stayed at the boundary between the plasma and cellular
      components in liquefied hematomas. We could also reproduce the same phenomenon in
      an experimental study using human blood. The characteristic dynamic motion of the
      contrast medium demonstrated in the liquefied hematoma, which we have called the
      "signal flare" phenomenon, is a significant sign indicating active bleeding.

PMID- 16954930
TI  - Primary bilateral adrenal lymphoma: 2 case reports.
AB  - Primary adrenal lymphoma is extremely rare. We describe 2 patients who presented
      with adrenal insufficiency or fever 'of unknown origin. Conventional imaging
      studies demonstrated bilateral bulky adrenal masses, and whole-body FDG positron
      emission tomography- computed tomography showed that the masses were the unique
      manifestation. Pathological diagnosis was non-Hodgkin lymphoma. The present cases
      indicated that primary adrenal lymphoma should be included in the differential
      diagnosis of bilateral adrenal masses.

PMID- 16954931
TI  - Preoperative multidetector computed tomography diagnosis of a seminoma
      originating from an undescended testis by "testicular vascular pedicle" sign.
AB  - We report a 65-year-old man with a palpable right lower quadrant mass who
      underwent multidetector computed tomography (MDCT) examination. Preoperative
      diagnosis of seminoma was possible by demonstration of "testicular vascular
      pedicle" sign by MDCT. We describe CT findings of the "testicular vascular
      pedicle" sign in this report.

PMID- 16954932
TI  - Magnetic resonance imaging of hepatocellular carcinoma mimicking focal nodular
      hyperplasia: a potential pitfall in patients with cirrhosis?
AB  - The magnetic resonance imaging findings in 2 cases of pathologically proven
      hepatocellular carcinoma that mimicked focal nodular hyperplasia are presented.
      Both cases were found in patients with cirrhosis, a condition in which focal
      nodular hyperplasia is unlikely to occur. Recognition that hepatocellular
      carcinoma may mimic focal nodular hyperplasia in patients with cirrhosis may
      prevent misdiagnosis and allow for earlier intervention.

PMID- 16954933
TI  - Multidetector computed tomography pulmonary angiogram in the assessment of
      myocardial infarction.
AB  - PURPOSE: The objective of this study is to evaluate the effectiveness of
      nonelectrocardiographic gated multidetector computed tomography (MDCT) performed
      for the purpose of assessment of pulmonary embolus in the evaluation of
      myocardial infarction (MI). METHODS: We retrospectively evaluated 147 consecutive
      patients who had a computed tomography angiogram for pulmonary embolus on a 16
      detector MDCT. Of this cohort, we determined 11 patients to have acute MIs based
      on electrocardiogram, positive troponin levels, and clinical findings and
      history. Four additional patients were found to have chronic MI based on history.
      The MDCT data were evaluated by an attending Radiologist, blinded to the clinical
      data, for quantitative and qualitative attenuations. Each MI was assigned a
      region of the heart based on its anatomical sections. RESULTS: We were able to
      detect 10 of 15 MIs, resulting in an overall sensitivity and specificity of 66.6%
      and 91.4%, respectively. The overall accuracy was 76.7%. If non-Q wave MIs are
      excluded from the data set, the sensitivity increased to 76.9%. Quantitative
      analysis of each region of the heart showed that there was a statistically
      significant difference (P < 0.01) between the infracting regions of the heart (69
      +/- 3.3 SEM) and those with normal perfusion (93.3 +/- 1.0 SEM). CONCLUSIONS:
      While this method did prove to be effective at determining patients who had an
      MI, the low sensitivity and inability to differentiate chronic from acute
      myocardial infarction suggest that this technique is very limited in clinical
      practice.

PMID- 16954934
TI  - Spectral coronary multidetector computed tomography angiography: dual benefit by
      facilitating plaque characterization and enhancing lumen depiction.
AB  - OBJECTIVE: To assess ex vivo specimens of atherosclerotic coronary arteries by
      dual energy (DE) multidetector computed tomography (MDCT) imaging, and to
      correlate depicted vessel lumen morphology and detected tissue characteristics
      with histopathologic analysis. METHODS: Coronary arteries were imaged on a 16
      slice MDCT using a DE protocol consisting of a 90- and 140-kV scan. Coronary
      arteries were perfused with iodine- and gadolinium-based contrast agents. The DE
      K-edge subtractions were performed. Regions-of-interest were placed on
      histopathologically/radiographically-matched vascular lumen and wall,
      fibromuscular and calcified plaque, and fat tissues. Vascular/tissue contrast-to
      noise ratios (CNR) were calculated, and their dependence on tissue type and
      contrast agent type was statistically evaluated. RESULTS: Tissue CNR analysis
      confirmed that all tissue types were successfully distinguished. Vascular wall
      and fibromuscular plaque achieved a significant increase in CNR ratios when DE
      techniques were used compared with 140 kV protocols. CONCLUSIONS: Spectral DE
      MDCT imaging of ex vivo atherosclerotic coronary arteries allows successful
      tissue characterization and enhances depiction of coronary lumen.

PMID- 16954935
TI  - Initial results on visualization of coronary artery stents at multiple heart
      rates on a moving heart phantom using 64-MDCT.
AB  - OBJECTIVE: Evaluation of the image quality of coronary artery stents at various
      heart rates using Multi Detector Computed Tomography (MDCT). METHODS: Nine
      different coronary stents were attached to a moving heart phantom and scanned
      using a 64-MDCT with a rotation time of 330 milliseconds (ms). The heart rate of
      the phantom was varied between 0 and 115 beats per minute (bpm). Two independent
      methods were used to investigate image quality. After reconstruction the average
      Houndsfield Unit (HU) value in the stent lumen was measured in the longitudinal
      and the cross-sectional plane. The stent images were then presented to two
      radiologists. The radiologists were asked to rank the images from good to bad
      based on lumen visibility and overall image quality. A second ranking was
      obtained using the CT density values. Finally two rankings were compared.
      RESULTS: Compared to the value for air, the HU-values measured in the lumen
      increased by 50 to 700 HU. Average slope value in the longitudinal plane was 1.7
      +/- 0.6 HU/bpm, and the average slope value in the cross-sectional plane was 1.7
      +/- 0.8 HU/bpm. This shows increased attenuation with increasing heart rate and
      thus a negative correlation between image quality and heart rate in both planes
      for all stents. The ranking acquired from the radiologists resembled the measured
      results as they also showed a negative correlation between the two variables.
      Using the results of the CT density measurements an analysis was done on multi
      segment reconstruction (MSR). CONCLUSION: A negative correlation between the
      heart rate and image quality of coronary stents was found by two independent
      methods. MSR showed no benefit for image quality in this study.

PMID- 16954936
TI  - Comparison of enhancement, image quality, cost, and adverse reactions using 2
      different contrast medium concentrations for routine chest CT on 16-slice MDCT.
AB  - OBJECTIVE: To evaluate the degree of enhancement and image quality of chest
      computed tomographic (CT) examinations on 16-slice multidetector CT using low
      concentration [300 milligrams of iodine per milliliter (mg I/mL)] and high
      concentration (370 mg I/mL) contrast media; to assess the impact on cost and
      adverse reactions of the use of high-iodine concentration contrast medium.
      MATERIALS AND METHODS: A total of 100 patients scheduled for routine chest CT
      examinations were administered nonionic contrast medium of 2 strengths: low
      iodine concentration contrast medium (300 mg I/mL) [group A: n = 50; male-female
      ratio, 28:22; mean age, 58.4 years] and high-iodine concentration contrast medium
      (370 mg I/mL) (group B: n = 50; male-female ratio, 18:32; mean age, 57.6 years)
      with a constant amount of iodine (400 mg) injected per kilogram of body weight.
      Contrast media were injected using a dual injector at 2.5 mL/s followed by a 30
      mL saline at 2.5 mL/s. The degree of enhancement was quantified by measuring
      Hounsfield unit values in different arteries and veins and was also rated on a 5
      point scale for qualitative assessment. We also evaluated perivenous contrast
      related artifacts. The data were compared using Mann-Whitney U test for both
      qualitative and quantitative enhancement ratings. A value of less than 0.05 was
      considered statistically significant. The value was adjusted using Bonferroni
      correction for statistical significance when multiple comparisons were performed.
      The difference in cost and the incidence of adverse reactions in both groups were
      calculated. RESULTS: The mean enhancement values in group B were significantly
      greater (P < 0.05) than those in group A. The mean Hounsfield units and standard
      deviation in groups A and B were aorta = 153 +/- 4, 216 +/- 20; pulmonary artery
      = 147 +/- 10, 208 +/- 20; superior vena cava = 155 +/- 27, 299 +/- 72; and
      pulmonary vein = 134 +/- 10, 215 +/- 30, respectively. The mean enhancement on a
      5-point scale was greater in group B (4.2) than in group A (3.3) (P < 0.01). No
      significant difference between groups in perivenous artifacts was seen. Up to
      5.5% savings in cost resulted from the use of a higher concentration of iodine,
      with no increase in adverse reactions. CONCLUSIONS: Use of higher-concentration
      contrast media provides a higher degree of contrast enhancement and image quality
      for a routine chest CT on a 16-slice multidetector CT. It also contributes to
      considerable cost savings with no increased risk of adverse reactions compared
      with low-concentration contrast media.

PMID- 16954937
TI  - Thin-section and low-dose volumetric computed tomographic densitometry of the
      lung in systemic sclerosis.
AB  - OBJECTIVE: To correlate lung density measurements with the results of visual
      assessment of thin-section computed tomography (CT) and of pulmonary function
      tests (PFT) in Systemic Sclerosis (SSc). METHODS: Thirty-nine SSc patients
      underwent sequential thin-section CT and spiral low-dose whole-lung acquisitions.
      The thin-section CT scans were evaluated with a dedicated visual scale. Mean lung
      density, skewness, and kurtosis were calculated from the lung density histogram.
      In addition from the spiral low-dose acquisition, the lung volume was computed.
      The visual score, the densitometric parameters, and the lung volume were
      correlated with the PFT. RESULTS: Mean lung density, skewness, and kurtosis
      computed from thin-section (R = 0,66; R = -0,74; R = -0,75) and low-dose
      volumetric (R = 0,72; R = -0,71; R = -0,71) CT and the lung volume (R = -0.54)
      correlated with the visual score. Densitometric values and lung volume
      consistently better correlated with PFT than the visual score. CONCLUSIONS: In
      SSc the histogram results are more closely correlated to PFT than the visual
      score. The low-dose spiral CT seems ideal for longitudinal studies.

PMID- 16954938
TI  - Lung diseases in patients with common variable immunodeficiency: chest
      radiographic, and computed tomographic findings.
AB  - OBJECTIVE: To evaluate chest radiographic and computed tomographic (CT) findings
      of lung disease related to common variable immunodeficiency. METHODS: Thirty-five
      chest radiographs and 30 CT scans of 46 patients were assessed. Lung parenchymal
      abnormalities that were evaluated included airspace consolidation, ground-glass
      attenuation, nodules, bronchiectasis, and air trapping. RESULTS: On CT, ground
      glass attenuation and nodules were the most frequent findings, observed in 60% (n
      = 18/30) and 83% (n = 25/30), respectively. Three major CT patterns were
      identified: airway disease (n = 13), nodules (n = 8), and parenchymal
      opacification (n = 6). All 13 patients with airway disease showed centrilobular
      opacities. One patient with peribronchial nodules showed lymphoid interstitial
      pneumonia, and 1 with randomly distributed nodules showed noncaseating
      granulomas. Patients with a CT pattern of parenchymal opacification showed lower
      lung predominance; surgical biopsies showed organizing pneumonia in 1 patient and
      lymphoid interstitial pneumonia with nonnecrotizing granulomas in another.
      CONCLUSIONS: Common variable immunodeficiency is associated with 3 major CT
      patterns: airway disease, nodules, and parenchymal opacification.

PMID- 16954939
TI  - A rare hernia of intra-abdominal fat in the thorax under an intact diaphragm:
      multidetector computed tomography.
AB  - Neither abdominal wall hernia nor diaphragmatic hernia is an unusual disease. But
      some may have difficulty diagnosing the presence of intra-abdominal fat in the
      thorax under an intact diaphragm. We report a case with an external compression
      of the right lower lung from intra-abdominal fat owing to a hernia through the
      right lateral abdominal wall and secondary through the ninth intercostal space of
      the chest wall to the right lower thorax without traumatic history. Multiple
      images, including multidetector row computed tomography, are reviewed.

PMID- 16954940
TI  - The crazy-paving pattern in granulomatous mycosis fungoides: high-resolution
      computed tomography-pathological correlation.
AB  - The purpose of this report is to describe a further distinctive cause of crazy
      paving pattern on thin-section computed tomography in a patient affected by
      pulmonary granulomatous mycosis fungoides. It was possible to reconcile the crazy
      paving appearance on thin-section computed tomography scan with the
      histopathologic pattern termed acute fibrinous organizing pneumonia pattern.

PMID- 16954941
TI  - Projection-based bolus detection for computed tomographic angiography.
AB  - Computed tomographic (CT) angiography is important for imaging studies on
      cardiovascular structures, peripheral vessels, and solid organs. In practice, a
      CT angiography scan is triggered by the bolus arrival at a prespecified
      anatomical location, which is determined using CT fluoroscopy. In this article,
      we propose a projection-based method adapted from the Grangeat formula to detect
      the bolus arrival. Then, we evaluate our new method in numerical and animal
      studies. Our results indicate that this method allows significantly better
      temporal resolution and is computationally more efficient, as compared with the
      image-based methods.

PMID- 16954942
TI  - Increased radiodensity of the proximal pole of the scaphoid: a common finding in
      computed tomography imaging of the wrist.
AB  - OBJECTIVES: To determine whether the proximal pole (PP) of the scaphoid is denser
      than the distal pole (DP) in a diverse population of patients undergoing computed
      tomography (CT) imaging of the wrist. METHODS: Sixty-nine patients who had CT of
      the wrist were retrospective reviewed. We measured CT density of the medullary
      bone of PP and DP of the scaphoid and calculated PP/DP ratio. To evaluate the
      variability of PP/DP ratio, we compared the ratios of these 3 groups. These
      patients were separated into 3 groups based on their diagnoses: group 1, healed
      scaphoids treated by casting; group 2, scaphoid nonunions; group 3, intact
      scaphoids. RESULTS: Proximal pole was denser than DP in most subjects. Proximal
      pole/distal pole ratio was similar among groups (P < 0.05). Fracture healing,
      sex, and age did not affect this ratio. However, we did not study scaphoids with
      avascular necrosis. CONCLUSIONS: Proximal pole was denser than DP in most of our
      subjects, including those with intact scaphoids, healing scaphoid fractures, and
      nonunions.

PMID- 16954943
TI  - 18Fluoro-deoxyglucose positron emission tomography evaluation of benign versus
      malignant osteochondromas: preliminary observations.
AB  - OBJECTIVE: To determine the contribution of 18fluoro-deoxyglucose positron
      emission tomography (18FDG PET) in distinguishing benign from malignant
      osteochondromas. MATERIALS AND METHODS: From 2000 to 2004, 10 patients (4
      females, 6 males, 12 to 64 years old) with osteochondromas were referred for
      whole body PET by clinicians for metabolic evaluation before planned surgery for
      pain or cosmesis. Two PET readers and 1 pathologist, blinded to their diagnoses
      and imaging studies (except for radiographs), correlated results post surgery.
      The PET average and maximum standard uptake value (SUV) generated by computer for
      Regions of Interest and correlated with radiographs, were based on axial 3.37 mm
      thick, 3 x 3 mm pixel images. Since SUVs vary from site to site depending on
      scanning devices and techniques, a 2.0 maximum cutoff SUV separated benign and
      malignant osteochondromas based on our standard protocols and specific equipment
      (Siemens Ecat Exact Knoxville, Tenn) used with our prior oncological studies.
      RESULTS: Results showed that no definitive statistical conclusions could be drawn
      due to the small number of patients involved, but they were, nevertheless, deemed
      promising. CONCLUSIONS: The 18FDG whole body PET aided the identification of
      malignant osteochondromas, their local recurrence and metastases by both
      displaying and quantifying their metabolic activity. Although the current study
      is limited by a small cohort, which precludes statistical analysis, additional
      experience with PET analysis of osteochondromas may further support its value as
      a physiological parameter supplementing anatomically based imaging modalities
      most often used for their evaluation.

PMID- 16954944
TI  - Intraarticular neurofibroma of the hip.
AB  - Musculoskeletal involvement in neurofibromatosis type 1 is present in 33% to 50%,
      including tumors of neural origin, typically neurofibroma. While both osseous and
      soft tissue lesions are well recognized, articular involvement is rare. The aim
      of this case report is describe and discuss the intraarticular extension of a
      neurofibroma into the hip joint.

PMID- 16954945
TI  - Evaluation and treatment of constipation in infants and children: recommendations
      of the North American Society for Pediatric Gastroenterology, Hepatology and
      Nutrition.
AB  - Constipation, defined as a delay or difficulty in defecation, present for 2 or
      more weeks, is a common pediatric problem encountered by both primary and
      specialty medical providers. The Constipation Guideline Committee of the North
      American Society for Pediatric Gastroenterology, Hepatology and Nutrition
      (NASPGHAN) has formulated a clinical practice guideline for the management of
      pediatric constipation. The Constipation Guideline Committee, consisting of two
      primary care pediatricians, a clinical epidemiologist, and pediatric
      gastroenterologists, based its recommendations on an integration of a
      comprehensive and systematic review of the medical literature combined with
      expert opinion. Consensus was achieved through Nominal Group Technique, a
      structured quantitative method. The Committee developed two algorithms to assist
      with medical management, one for older infants and children and the second for
      infants less than 1 year of age. The guideline provides recommendations for
      management by the primary care provider, including evaluation, initial treatment,
      follow-up management, and indications for consultation by a specialist. The
      Constipation Guideline Committee also provided recommendations for management by
      the pediatric gastroenterologist.

PMID- 16954946
TI  - Gastrointestinal tract as a target organ for orally administered insulin.
AB  - The intestine is not considered to be a classic target tissue for insulin. Recent
      in vitro and in vivo experiments suggest that intestinal as well as systemic
      effects are observed following oral administration of insulin. Local effects
      include enhancement of intestinal growth, cell maturation, enzyme expression, gut
      adaptation after intestinal resection and reduction of intestinal permeability.
      Systemic effects, at least in animal models, include favorable effects on blood
      glucose and lipid profile and on the prevention of autoimmunity and attenuating
      the atherosclerotic process.

PMID- 16954947
TI  - Next steps on the thiopurine methyltransferase 6-thioguanine nucleotide pathway.

PMID- 16954948
TI  - Effects of prenatal lipopolysaccharide exposure on epithelial development and
      function in newborn rat intestine.
AB  - BACKGROUND: Maternal infection during pregnancy is associated with several
      neonatal morbidities, including periventricular leukomalacia and lung
      maldevelopment and injury. OBJECTIVE: To test the hypothesis that responses to
      prenatal maternal exposure to lipopolysaccharide (LPS) alter intestinal
      epithelial development and function in newborn rats. DESIGN/METHODS: Timed
      pregnancy female Sprague-Dawley rats were administered either 2 mg LPS or an
      equal volume of isotonic saline by intraperitoneal injection at E16 and allowed
      to deliver naturally. Pups were weighed and then killed at days of life (DOL) 0,
      3, 7 and 14. Morphometric parameters were measured on standard hematoxylin and
      eosin-stained sections using ImagePro software. Immunohistochemistry was
      performed with antibody specific for inducible nitric oxide synthase (iNOS) and 3
      nitrotyrosine on distal ileal intestinal samples analyzed at each time point.
      Optical density was determined and quantified for site-specific regions of
      intestinal sections. On DOL 14, in vivo mucosal permeability was measured by
      feeding rats fluorescein isothiocyanate (FITC) via orogastric tube; and then
      serum FITC was measured. RESULTS: There were no significant differences in pup
      weights. Mucosal thicknesses were significantly less in the distal ileum from
      pups born to LPS-exposed dams on DOL 0, 3 and 7 (P < 0.001). On DOL 0, iNOS
      protein concentrations in the prenatal LPS treatment group were significantly
      greater than iNOS protein concentrations in the distal villus (P < 0.001),
      proximal villus/crypts (P < 0.01), submucosa (P < 0.001) and muscularis (P <
      0.01) in the distal small intestine of the control group. On DOL 3, 7 and 14,
      significant differences were observed in iNOS protein concentrations in the
      distal villus and submucosal regions between groups (P < 0.001). On DOL 0, 3, 7
      and 14, 3-nitrotyrosine immunostaining was significantly elevated in the prenatal
      LPS-exposed pups in the distal villus on (P < 0.001) as well as in the submucosa
      on DOL 3 (P < 0.001). Serum FITC measurement was significantly greater in
      prenatal LPS exposure group at DOL 14 (P < 0.001). CONCLUSIONS: Maternal exposure
      to LPS during pregnancy alters intestinal growth and regulation of iNOS in the
      newborn rat intestine.

PMID- 16954949
TI  - Effect of esophageal ligation on small intestinal development in normal and
      growth-retarded fetal rabbits.
AB  - OBJECTIVE: The uninterrupted passage of amniotic fluid through the
      gastrointestinal tract is hypothesized to influence both intestinal and overall
      fetal somatic development. The effect of in utero esophageal ligation (EL) and
      therefore the exclusion of AF on somatic growth, small intestinal (SI) morphology
      and proliferation, and the expression of the glucose transporter sodium-glucose
      cotransporter 1 (SGLT-1) in both normal and intrauterine growth-retarded (IUGR)
      fetal rabbits were evaluated. METHODS: Thirteen pregnant New Zealand white
      rabbits underwent surgery on day 24 of their normal 31-day gestation. Ipsilateral
      normal and IUGR fetuses underwent EL; the contralateral normal and IUGR fetuses
      underwent cervical exploration only forming 4 study groups (control-normal,
      control-IUGR, EL-normal and EL-IUGR). Rabbits were killed on day 31. Small
      intestinal villus height was measured, and epithelial cell proliferation was
      deter mined by proliferating cell nuclear antigen staining. Sodium-glucose
      cotransporter 1 messenger RNA (mRNA) and protein expressions were analyzed.
      Statistical analysis was performed using 2-way analysis of variance. RESULTS:
      Esophageal ligation reduced fetal weight in IUGR by 15% and in normal by 10%.
      Villus height was significantly reduced in IUGR versus normal in both control and
      EL (control, P = 0.01; EL, P = 0.05). Intrauterine growth-retarded fetuses had
      reduced SI proliferation versus normal in both control and EL. Sodium-glucose
      cotransporter 1 mRNA production in EL fetuses was equal to control fetuses.
      Esophageal ligation-normal and EL-IUGR fetuses exhibited reduced protein levels
      and decreased staining for SGLT-1 in villus enterocytes. CONCLUSIONS: Amniotic
      fluid exclusion by in utero EL reduced fetal weight. Small intestinal
      proliferation was not affected by EL. Although SGLT-1 mRNA and protein were
      produced in all 4 groups, exposure of the fetal gastrointestinal tract to
      amniotic fluid appears necessary for proper brush border expression of nutrient
      transporter proteins.

PMID- 16954951
TI  - Subclinical exocrine pancreatic dysfunction resulting from decreased
      cholecystokinin secretion in the presence of intestinal villous atrophy.
AB  - The aim of this study was to evaluate the concept that pancreatic dysfunction in
      patients having gluten sensitivity (celiac disease [CD]) or cow's milk protein
      enteropathy (CMPE) may result from the lack of pancreatic enzyme stimulation in
      the absence or decrease of cholecystokinin (CCK) secretion caused by villous
      atrophy. PATIENTS AND METHODS: The following parameters were measured: plasma CCK
      in response to a fatty meal and human pancreatic fecal elastase in 24 patients
      with CD while on gluten-free diet and after gluten provocation and in 12 patients
      with CMPE at diagnosis and after a 6-month period of cow's milk-free diet.
      Intestinal mucosa morphology was examined by small bowel biopsy. Sixty-three
      controls having no organic gastrointestinal problems were investigated once at
      the time of diagnostic evaluation. RESULTS: Fasting CCK, obtained at a time when
      patients with CD or CMPE had normal intestinal mucosa, was significantly
      different from postprandial and comparable to that of the control group. Fasting
      CCK obtained from patients with villous atrophy was also statistically different,
      but not significantly, from the postprandial. Fasting and postprandial plasma CCK
      and fecal pancreatic elastase values from patients having normal intestinal
      mucosa were significantly higher than those obtained from patients with villous
      atrophy. Significant correlation of intestinal mucosa morphology and CCK with
      fecal elastase concentration was documented. CONCLUSION: Exocrine pancreatic
      dysfunction in individuals having villous atrophy may be the consequence of
      decreased CCK secretion. Cholecystokinin and pancreatic secretion is restored to
      normal, with intestinal mucosa regeneration.

PMID- 16954950
TI  - Analysis of CFTR, SPINK1, PRSS1 and AAT mutations in children with acute or
      chronic pancreatitis.
AB  - OBJECTIVES: Defects of PRSS1, SPINK1, CFTR and AAT are considered causative or
      predisposing to pancreatitis. The aim of this study was to evaluate the impact of
      these defects into molecular pathology of chronic pancreatitis (CP) and acute
      recurrent pancreatitis (ARP). METHODS: Ninety-two children with CP or ARP, 55
      family members and 50 controls were investigated. The subjects were screened for
      PRSS1 mutations: R122H, R122C, A16V, N29I; SPINK1 N34S variant; panel of 14 CFTR
      defects: INNOLiPA CFTR12, CFTRdele2,3 and IVS8-T variant or panel of 3 CFTR
      defects-F508del, CFTRdele2,3 and IVS8-T; AAT mutations: E264V, E342K. RESULTS: We
      identified 1 mutated allele in at least 1 of 4 genes in 31 of 92 patients and 12
      of 50 controls (P = 0.157). Mutations in SPINK1 and PRSS1 were most frequent.
      PRSS1 mutations were identified mainly in CP patients (9.6% of CP vs 2.5% of ARP
      alleles, P = 0.094), whereas N34S SPINK1 mutation was present with comparable
      frequency in CP and ARP patients (7.7% vs 10.0%, P = 0.768). The frequency of
      mutations in CFTR alleles was similar to controls (4.9% vs 5%, P = 0.587).
      Overall frequency of AAT mutations was lower than in the controls. Family studies
      showed that defects in the examined genes did not always segregate with disease.
      CONCLUSIONS: PRSS1 defects seem to be causative for pancreatitis, whereas defects
      in SPINK1 are suggested to be associated with the disease. No association between
      CFTR mutations and pancreatitis was observed. The importance of AAT variants
      remains speculative.

PMID- 16954952
TI  - Clinical features of celiac disease in Indian children: are they different from
      the West?
AB  - OBJECTIVE: This study was designed to prospectively evaluate the clinical
      features of celiac disease (CD) in a large group of Indian children and to
      compare them with those from the West. PATIENTS AND METHODS: Over a period of 5
      years, a total of 549 children (< or = 14 years) with a clinical suspicion of CD
      were evaluated. Their detailed clinical features, investigations, and follow-up
      data were recorded. Complete hemogram, endoscopic duodenal biopsy, and celiac
      serology were done in all of the cases. Celiac disease was diagnosed on the basis
      of modified European Society of Paediatric Gastroenterology, Hepatology and
      Nutrition criteria. RESULTS: Celiac disease was diagnosed in 300 children; 39
      were excluded because of lack of follow-up or poor response to gluten-free diet.
      The remaining 210 had normal villous architecture and served as controls. The
      mean (+/- standard deviation) age of children with CD was 6.7 +/- 3 years, and
      the mean duration of symptoms was 3.5 +/- 2.5 years. The majority (84%) presented
      with diarrhea; other features were failure to thrive in 91%, anemia in 84%,
      wasting in 87%, and stunting in 60% of cases. Among the serological tests, the
      best results were obtained with tissue transglutaminase. On follow-up (19.4 +/-
      15.5 months), symptoms subsided in all cases of CD with a significant weight and
      height gain. CONCLUSIONS: Indian children with CD present late, with a
      significant delay in diagnosis. The majority presents with classic symptoms of
      diarrhea, failure to thrive, and anemia. There is a need for increasing awareness
      to pick up the atypical forms of the disease.

PMID- 16954953
TI  - Abnormal fatty acid pattern in intestinal mucosa of children with celiac disease
      is not reflected in serum phospholipids.
AB  - OBJECTIVE: Celiac disease (CD) is characterized by chronic inflammation of the
      small intestinal mucosa with disturbed epithelial transport. The fatty acid (FA)
      composition of intestinal membranes is important for epithelial function, and
      disturbances may contribute to the pathophysiology of the disease. We aimed to
      evaluate whether the intestinal mucosal FA status was reflected in serum
      phospholipids of patients with CD. PATIENTS AND METHODS: Samples were obtained
      from 7 pediatric patients with active CD showing mucosal atrophy, 6 pediatric
      patients with CD in remission, and 11 control pediatric patients with
      morphologically healthy intestinal mucosa. Small intestinal biopsies were
      obtained using a Watson biopsy capsule under fluoroscopic control. Blood samples
      were collected on the same morning after an overnight fast. Tissue phospholipids
      were isolated by high-performance liquid chromatography, and FAs were analyzed by
      capillary gas-liquid chromatography. RESULTS: Serum phospholipid FA showed
      marginal differences between the patients with CD and the controls. Significant
      differences were observed in mucosa with active CD compared with controls.
      Linoleic acid (18:2n-6) level was decreased, whereas those of its derivatives
      were elevated, indicating increased transformation of n-6 FA. Mead acid (20:3n-9)
      level was increased, with an increased ratio of Mead acid to arachidonic acid
      (20:4n-6) levels, suggesting essential fatty acid deficiency. The n-3 FA levels
      were not significantly changed. During remission, the FA pattern of the
      intestinal mucosa was mainly similar to that in controls. CONCLUSIONS: The FA
      abnormality of intestinal mucosa in patients with active CD was not reflected in
      serum values. Altered FA content may contribute to the pathophysiology of the
      disease because FAs are important for enzymes and for the transport and receptor
      functions of epithelial membranes.

PMID- 16954954
TI  - Evolution of thiopurine use in pediatric inflammatory bowel disease in an
      academic center.
AB  - OBJECTIVES: We evaluated how our use of thiopurines was altered by determination
      of thiopurine methyltransferase (TPMT) level and drug dose adjustment guided by a
      6-mercaptopurine metabolite assay. We further examined whether these resulted in
      better selection of the drug dose, improved control of disease, and decreased
      corticosteroid use in pediatric inflammatory bowel disease (IBD). PATIENTS AND
      METHODS: This is a retrospective review of 101 pediatric patients with IBD
      receiving a stable dose of azathioprine (AZA) for 4 months or longer. The study
      group (n = 64) consisted of patients who received AZA and had metabolite levels
      measured. The comparison group (n = 37) consisted of patients who were receiving
      AZA before the availability of metabolite measurement. The TPMT level was
      measured in study group patients before starting AZA. RESULTS: Patients with
      normal TPMT level received a higher starting dose of AZA than in patients who
      were heterozygous for TPMT deficiency (1.7 vs 0.9 mg/[kg x d], P < 0.0001). Study
      group patients received a higher starting dose (1.6 vs 1.2 mg/[kg x d], P =
      0.001) and a higher final dose of AZA (2.4 vs 1.7 mg/[kg x d], P < 0.0001)
      compared with patients in the comparison group. These patients also had more dose
      adjustments (0.8 vs 0.4 mg/kg, P < 0.002). The number of disease exacerbations
      per patient per year was 55% less in the study group (95% CI, 17%-76%, P <
      0.0001). The study group patients received less prednisone (P < 0.0001) and had
      lower disease activity scores (P < 0.05). There was no difference between groups
      in infliximab use or surgery rate. CONCLUSIONS: Azathioprine dose adjustment
      using a 6-mercaptopurine metabolite assay was associated with use of higher
      doses, improved control of disease and decreased corticosteroid use in pediatric
      patients with IBD.

PMID- 16954955
TI  - Acid and nonacid gastro-oesophageal reflux in neurologically impaired children:
      investigation with the multiple intraluminal impedance procedure.
AB  - OBJECTIVES: The diagnosis of gastro-oesophageal reflux (GOR) is more difficult in
      children with neurological impairment because symptoms are often less
      interpretable and frequently go undetected. The use of combined pH and multiple
      intraluminal impedance allows for the detection of both acid (pH < 4) and nonacid
      (pH > 4) GOR episodes, in addition to the height of the refluxate and the total
      acid and bolus clearance time in this cohort. METHODS: Sixteen neurologically
      impaired children (9 were fed nasogastrically, 7 were fed orally) underwent 12
      hour combined pH and multiple intraluminal impedance. RESULTS: There were a total
      of 425 reflux episodes during the study period, of which 239 (56.2%) were
      nonacid. The median of reflux episodes per hour was 1.8 (range, 0.2-6.3/h). The
      median height of the refluxate was 1.5 channels (range, 1.1-2.9); and 71.3% of
      reflux episodes reached the upper oesophagus, of which 52.4% were nonacid reflux
      events. On average there were more GOR events (both acid and nonacid) in the
      children who were fed via a nasogastric tube, and the median height of refluxate
      was also higher in this group. However, the median acid clearance time was longer
      (both proximal and distal) in the children who were fed orally (28.6 s vs 16.2 s
      proximally; 67.9 s vs 38.3 s distally). The median acid clearance time (21.7 s
      proximally; 39.5 s distally) was longer when compared with bolus clearance (14.9
      s). CONCLUSIONS: More than half of the reflux events in neurologically impaired
      children are nonacidic and would therefore go undetected by conventional pH
      metry. There are more reflux events in children fed nasogastrically than oral-fed
      children.

PMID- 16954956
TI  - Pepsin, a reliable marker of gastric aspiration, is frequently detected in
      tracheal aspirates from premature ventilated neonates: relationship with feeding
      and methylxanthine therapy.
AB  - OBJECTIVES: To determine the frequency of pepsin detection in tracheal aspirate
      (TA) samples of mechanically ventilated premature neonates and its association
      with feedings and methylxanthine therapy. PATIENTS AND METHODS: Serial TA samples
      (days 1, 3, 5, 7, 14, 21, 28 and >28 days) were collected from premature neonates
      receiving ventilatory support. An enzymatic assay with a fluorescent substrate
      was used to detect pepsin. Pepsin was also measured in 10 serum samples collected
      in conjunction with the TA samples from 8 neonates. RESULTS: A total of 239 TA
      samples was collected from 45 premature neonates (mean birth weight, 762 +/- 166
      g; mean gestational age, 25.5 +/- 1.5 wk). Pepsin was detectable in 222 of 239 TA
      samples (92.8%) and in none of the serum samples. Pepsin was significantly lower
      on day 1 (mean, 170 +/- 216 ng/mL) when compared with all other time points (P <
      0.05). Mean concentration of pepsin was significantly lower when infants were
      unfed (265 +/- 209 ng/mL) compared with levels during feeding (390 +/- 260 ng/mL,
      P = 0.02). The mean level of pepsin was significantly higher in infants during
      xanthine therapy (419 +/- 370 ng/mL) compared with no xanthine therapy (295 +/-
      231 ng/mL, P = 0.037). CONCLUSION: Pepsin, a marker of gastric contents, was
      detected in more than 92% of TA samples from premature infants on mechanical
      ventilation. The level of pepsin was higher in fed infants when compared with
      unfed infants. Xanthine therapy was also associated with increased pepsin in TA
      samples. Chronic aspiration of gastric contents may worsen lung disease in
      premature infants.

PMID- 16954957
TI  - Relationship between viral load and genotypes of hepatitis B virus in children
      with chronic hepatitis B.
AB  - OBJECTIVE: We evaluated the prevalence and clinical significance of hepatitis B
      virus (HBV) genotypes in children with chronic hepatitis B. METHODS: Hepatitis B
      virus genomes of 249 hepatitis Be antigen-positive chronic hepatitis B surface
      antigen carriers were genotyped based on restriction fragment length
      polymorphism. Genotypes were correlated with corresponding values for alanine
      aminotransferase levels, quantitative HBV DNA and histological findings. RESULTS:
      One hundred and sixty-two boys and 87 girls (mean age, 7.2 years) were studied.
      Ninety-six percent were attributed to HBV genotypes A (32.5%) or D (63.5%). The
      remaining were classified as genotypes B, C, E and F. There was no significant
      difference in both alanine aminotransferase levels and histological findings
      among different genotypes. However, there was a clear association between very
      high HBV DNA levels and individuals with genotype D (P = 0.006). Mean time follow
      up of 3.6 years showed later anti-HBe seroconversion in patients with genotype D
      than in those with genotype A (58% vs 37%). CONCLUSIONS: Compared with children
      with genotype A, children with genotype D showed a significantly higher viral
      load. Inasmuch as a relationship exists between viral load and response to
      treatment in children infected through vertical transmission, children with
      genotype D have to be carefully monitored. Long-term studies are needed to
      determine whether these patients are at risk of a poorer outcome.

PMID- 16954958
TI  - Visual loss and idiopathic intracranial hypertension in children with Alagille
      syndrome.
AB  - BACKGROUND: Alagille syndrome (AGS) is an autosomal dominant, multisystem
      disorder defined by developmental abnormalities of the liver, heart, eye and
      skeleton. Although visual problems are recognised, the severity of visual loss
      and its link with idiopathic intracranial hypertension (IIH) has not been
      reported. AIM: To review the incidence of visual loss and IIH in children with
      AGS managed at a National Paediatric Liver Unit between 1989 and 2004. SUBJECTS
      AND METHODS: Retrospective case note review of children who fulfilled criteria
      for diagnosis of AGS and had an ophthalmic examination by a paediatric
      ophthalmologist. RESULTS: Fifty-five children with AGS were evaluated. Of these,
      41 children fulfilled diagnostic criteria and had a documented ophthalmic
      examination. Six children had undergone liver transplantation. Three children had
      a definite diagnosis of IIH, 2 of whom developed postliver transplant. All 3 were
      treated medically, but 1 child with IIH required lumboperitoneal shunting. All 3
      children with definite IIH have normal vision after treatment. Another child with
      probable undiagnosed IIH has bilateral optic atrophy and is registered blind. Two
      children with AGS are registered partially sighted, one with rod cone dystrophy
      and the other with pigmentary retinopathy and right disc atrophy. SUMMARY:
      Although visual abnormalities are well described in children with AGS, a minority
      of children have significant progressive visual loss. Idiopathic intracranial
      hypertension has been identified as a potentially treatable precipitating factor.
      CONCLUSIONS: We recommend annual fundoscopy in the follow-up of children with AGS
      to facilitate early detection and appropriate management of IIH to prevent visual
      loss.

PMID- 16954959
TI  - Azathioprine monotherapy for maintenance of remission in pediatric patients with
      autoimmune hepatitis.
AB  - Autoimmune hepatitis (AIH) is a chronic disorder characterized by unresolving
      liver inflammation and has a fluctuating clinical course. Standard therapy has
      been corticosteroids given daily, alone or in combination with azathioprine
      (AZA). The potential for significant side effects from prolonged corticosteroid
      use remains high. To date, no pediatric literature describes long-term AZA
      monotherapy after induction of remission with corticosteroids. We conducted a
      retrospective chart review from 1990 to 2002, which revealed 8 patients with AIH.
      Three patients were excluded because of other diseases requiring continued or
      intermittent use of corticosteroids. The time to complete biochemical remission
      on corticosteroids and AZA was 230 days (range, 74-288 days). Azathioprine was
      introduced early following the diagnosis (range, 1-35 days). All 5 patients were
      successfully weaned off corticosteroids after a median of 378 days and were
      maintained on AZA monotherapy for a median of 37 months (range, 28-82 months).
      One patient had a disease exacerbation on AZA monotherapy 75 months after the
      discontinuation of corticosteroids. She responded quickly to a corticosteroid
      burst and has been on AZA monotherapy for 7 months. One patient relapsed after
      self-discontinuing all medications. Long-term remission of AIH was possible in
      our case series with the early introduction and maintenance treatment with AZA as
      monotherapy.

PMID- 16954960
TI  - Zinc supplementation for the treatment of diarrhea in infants in Pakistan, India
      and Ethiopia.
AB  - OBJECTIVE: This randomized, placebo controlled trial was designed to assess the
      safety and efficacy of 10-mg zinc supplementation for the treatment of acute
      diarrhea in infants. METHODS: A total of 1110 infants aged 28 days to 5 months
      with acute diarrhea were enrolled and randomized to receive either zinc (n = 554)
      or placebo (n = 556) for 14 days. Diarrhea history, anthropometric status, breast
      feeding status and socioeconomic indicators were assessed at baseline. The homes
      of all infants were visited every 3 days until the diarrhea episode was over. The
      number of stools, presence of blood and additional illnesses were recorded daily.
      RESULTS: The geometric mean duration of the diarrhea episode was 0.21 days longer
      among infants receiving zinc versus those receiving placebo, but this was not
      statistically significant and no difference was observed after controlling for
      sex, exclusive breast-feeding and length for age Z score. There were no
      differences in any subgroup (ie, sex, baseline length for age Z score, exclusive
      breast-feeding or site after controlling for the remaining subgroup variables).
      There were no differences in reported stool frequency or among the proportion of
      episodes lasting longer than 7 days. Rates of vomiting were similar in the zinc
      and placebo groups. CONCLUSIONS: Young infants do not appear to benefit from zinc
      supplementation for the treatment of diarrhea.

PMID- 16954961
TI  - Adequacy and safety of an infant formula with a protein/energy ratio of 1.8 g/100
      kcal and enhanced protein efficiency for term infants during the first 4 months
      of life.
AB  - OBJECTIVE: Excess protein in infant formula may lead to renal overload and play a
      role in later obesity. The objective of this controlled, prospective, randomized,
      double-blind study was to assess the suitability and safety of a modified protein
      content infant formula and its noninferiority as compared to a conventional
      formula. PATIENTS AND METHODS: Healthy term infants age < 7 days were either
      breast-fed or randomized to be fed exclusively with a conventional casein
      predominant formula (protein/energy ratio: 2.6 g/100 kcal) or the isocaloric whey
      predominant study formula (protein/energy ratio: 1.8 g/100 kcal) for 120 days.
      Primary outcome was daily weight gain between D0 and D120 (noninferiority
      criterion: difference in daily weight gain < or = 4 g). Secondary outcomes were
      daily gain in weight, length, head circumference and body mass index at monthly
      intervals. Tolerance and safety were assessed at each visit. RESULTS: 162 infants
      were enrolled, 84% of the formula-fed infants and 36% of the breast-fed infants
      completing the study. Mean daily weight gain from D0 to D120 in the formula-fed
      groups differed by 0.38 g/day [95% CI: -2.59; 1.83] signifying the noninferiority
      of the study formula. Secondary outcomes did not differ between the 2 groups at
      any time and were comparable to outcomes in the breast-fed group. Tolerance was
      good and adverse events were not different between study groups. CONCLUSIONS: The
      whey-predominant study infant formula with a protein/energy ratio of 1.8 g/100
      kcal and enhanced protein efficiency is safe and not inferior to a conventional
      formula in ensuring normal growth during the first four months of life.

PMID- 16954962
TI  - Oligosaccharides in colostrum of Italian and Burkinabe women.
AB  - Human milk contains a large number of compounds to provide nutrition and defense
      for the newborn. Among these, oligosaccharides are present in concentrations up
      to 12 g/L, and their composition varies during lactation. Colostrum from 53
      Burkinabe women were collected at the maternity department of St Camille Medical
      Centre in Ouagadougou (Burkina Faso, West Africa). Colostrum from 50 Italian
      women were collected at the maternity department of St Bambino Hospital in
      Catania (Catania, East Sicily, Italy). All mothers spontaneously delivered at
      term. Italian mothers received an injection of the ergot derivative ergotamine
      after delivery. Ergotamine, notoriously, delays breastfeeding initiation up to 2
      to 3 days. Chromatographic separation of colostrum from both Burkinabe and
      Italian women showed a progressive appearance of oligosaccharides in the first 3
      days. Burkinabe women showed high concentrations of 2-fucosyllactose and lower
      concentrations of lacto-N-fucopentaose I. By contrast, Italian women showed
      inverted behaviour. A comparable percentage of the secretor genotype for the
      Lewis blood group phenotype in both Burkinabe and Italian women was found.
      According to the different ethnicity, different milk oligosaccharide profiles
      were documented in the present study. 2-Fucosyllactose in milk should be
      biologically significant for Burkinabe infants because of the high levels found
      in their mothers' colostrum after the second day of lactation.

PMID- 16954963
TI  - Breast-feeding in Athens, Greece: factors associated with its initiation and
      duration.
AB  - OBJECTIVES: To determine the prevalence, examine the influence of hospital
      practices and investigate potential determinants of breast-feeding in Athens.
      PATIENTS AND METHODS: Three hundred twelve mothers provided information regarding
      feeding practices at certain maternity hospitals in Athens, at 40 days and 6
      months postpartum. Multiple logistic regression analysis was performed to
      evaluate the association between the initiation and maintenance of breast-feeding
      and potential risk factors. RESULTS: Although almost 90% of newborn infants were
      given a breast milk substitute one or more times during the first 2 days at the
      maternity hospital, the exclusive breast-feeding percentage on the last day of
      hospital stay reached 85%. Breast-feeding and exclusive breast-feeding
      percentages dropped to 55% and 35%, respectively, at 40 days postpartum and to
      16% and 12%, respectively, at 6 months postpartum. While in the hospital, 3% of
      mothers initiated breast-feeding within 1 hour of labor, only 34% were informed
      about the advantages of breast-feeding by health professionals and 42% were
      trained to breast-feed by the midwives. "Rooming-in" was not practiced in the
      private hospitals. The educational level was positively associated with the
      initiation of breast-feeding [odds ratio (OR): 1.36, confidence interval (CI):
      1.02-1.81], the mother's body mass index was negatively associated with the
      maintenance of breast-feeding for 40 days (OR: 0.56, CI: 0.32-0.98) and 6 months
      (OR: 0.28, CI: 0.06-1.26) and a caesarean section was negatively associated with
      the initiation (OR: 0.24, CI: 0.11-0.49) and maintenance of breast-feeding (OR:
      0.42, CI: 0.20-0.89). CONCLUSIONS: Breast-feeding is not appropriately supported
      in certain maternity hospitals in Athens, and this is probably the cause of
      observed low breast-feeding prevalence.

PMID- 16954964
TI  - Severe gastric outlet obstruction in a child with ectopic pancreas: is there a
      role for Helicobacter pylori?

PMID- 16954965
TI  - Infliximab as first-line therapy in severe pediatric Crohn disease.

PMID- 16954966
TI  - Wegener granulomatosis mimicking inflammatory bowel disease in a pediatric
      patient.

PMID- 16954967
TI  - Serial transverse enteroplasty for management of refractory D-lactic acidosis in
      short-bowel syndrome.

PMID- 16954968
TI  - Evaluation of a urine-based enzyme-linked immunosorbent assay test for the
      detection of Helicobacter pylori infection among 3- to 5-year-old Israeli Arab
      healthy children.
AB  - We conducted a community-based study among 159 healthy Israeli Arab children aged
      3 to 5 years old to examine the validity of the HpELISA kit (URINELISA, Otuska
      Phamaceuticals Co, Ltd, Tokyo, Japan) for detection Helicobacter pylori IgG
      antibodies in urine. The polyclonal H. pylori stool antigen test (Premier HpSA)
      served as the gold standard. The sensitivity, specificity, positive and negative
      predictive values of the URINELISA kit were 34.2%, 96.3%, 90% and 60%,
      respectively. Using a cutoff value calculated based on the receiver operating
      characteristic curve (0.066), the corresponding figures were 65.8%, 87.5%, 83%
      and 72%, respectively. These data indicate that the usefulness of the URINELISA
      test in epidemiological studies in healthy young children is limited.

PMID- 16954969
TI  - Antiemetics for children with gastroenteritis: off-label but still on in clinical
      practice.
AB  - Antiemetics are not included for treatment of vomiting associated with acute
      gastroenteritis (AGE) in children by standard guidelines. We performed a survey
      to determine antiemetic prescribing rates by Italian pediatricians. A structured
      questionnaire was distributed at a pediatric national conference. The majority of
      responders reported prescribing antiemetics for pediatric gastroenteritis.
      Although there is insufficient evidence to justify their use, the use of
      antiemetics is widely present among pediatricians.

PMID- 16954970
TI  - Evaluation and treatment of constipation in children: summary of updated
      recommendations of the North American Society for Pediatric Gastroenterology,
      Hepatology and Nutrition.
AB  - Constipation is a common pediatric problem. To assist health care professionals
      who care for children with constipation, the North American Society for Pediatric
      Gastroenterology, Hepatology and Nutrition (NASPGHAN) previously published a
      clinical guideline based on an integration of medical evidence with expert
      opinion. To evaluate studies published since then, the NASPGHAN Constipation
      Guideline Committee performed a comprehensive and systematic review of the
      medical literature since 1997, to identify, review and rate the quality of new
      evidence. Based on this review, the recommendations of the original clinical
      guideline were reaffirmed with several modified according to the new evidence.
      Below is a summary of the evidence reviewed for this update. The complete revised
      guideline is available online in its entirety.

PMID- 16954972
TI  - Have you reached JCAHO's 2006 National Patient Safety Goals?

PMID- 16954973
TI  - The joys and responsibilities of preceptors.

PMID- 16954974
TI  - Outcomes in laryngeal cancer: a product of the learning curve?

PMID- 16954975
TI  - Use of intradermal dilutional testing and skin prick testing: clinical relevance
      and cost efficiency.
AB  - OBJECTIVES/HYPOTHESIS: The objective was to determine the agreement of the
      positive results from a multiple skin prick test (SPT) device with the ability to
      determine a definable endpoint through intradermal dilutional testing (IDT) to
      compare semiquantitatively the degree of positivity of SPT results with
      quantitative results from IDT and to analyze the cost of immunotherapy based on
      SPT compared with IDT guided by SPT. STUDY DESIGN: Retrospective review of
      clinical data (random accrual). METHODS: One hundred thirty-four patients
      underwent allergy screening using a multiple SPT device. Antigens testing
      positive by skin prick device were tested using IDT on a separate day. Antigens
      testing negative by SPT were not evaluated by IDT. Regional allergy testing
      practice patterns were determined, and a cost analysis using Medicare rates was
      performed RESULTS: There was good agreement between an antigen testing positive
      by SPT and the determination of a definable endpoint (93.33%, n = 1,334
      antigens). The degree of positivity from the SPT correlated poorly with the final
      endpoint concentration (r = 0.40, P < .0001). Blended testing techniques were
      similar in cost when compared with several commonly used allergy testing
      protocols. CONCLUSIONS: Antigens which show reactivity to a multiple SPT device
      usually have a treatable endpoint that is independent of the degree of positivity
      of the SPT result. IDT is an important step in the determination of the strongest
      starting dose of immunotherapy that may be safely administered. Initiating
      immunotherapy in this manner may potentially create significant health care
      savings by shortening the time required for a patient to reach their individual
      maximally tolerated dose. The use of a relatively large screening panel is cost
      effective and does not increase the average number of antigens treated by
      immunotherapy. Blended allergy testing techniques that include IDT in their
      protocol are comparable in cost with commonly used allergy testing protocols.

PMID- 16954976
TI  - Diagnostic testing for vocal fold paralysis: survey of practice and evidence
      based medicine review.
AB  - OBJECTIVES/HYPOTHESIS: Vocal fold paralysis continues to be a dominant topic in
      laryngology. Although the majority of cases can be attributed to a known
      etiology, a significant number of patients present without a clear precipitating
      event. Over 1,500 studies regarding vocal fold paralysis exist in the medical
      literature, although only a small percentage report on the use of serum or
      radiographic testing for the evaluation of idiopathic paralysis. Despite this,
      patients are routinely subjected to diagnostic evaluation to investigate the
      underlying cause. To characterize contemporary practice, a national survey of the
      American Broncho-Esophagological Association (ABEA) membership was undertaken. It
      is hypothesized that the current practice of diagnostic testing for idiopathic
      vocal fold paralysis is not well supported by an evidence-based medicine (EBM)
      review of the available medical literature. STUDY DESIGN: The authors conducted a
      national survey, systematic EBM review of existing literature. METHODS: Surveys
      were mailed to all active ABEA members; responses regarding practice
      specialization as well as serum/radiographic diagnostic preferences for
      idiopathic vocal fold paralysis were tabulated and subjected to statistical
      analysis. To compare contemporary practice with evidence in the available
      literature, an EBM review was first performed. Articles for evaluation were
      selected from a Medline search of English-language abstracts related to adult
      vocal fold paralysis. The publications were individually reviewed and an EBM
      level and grade were assigned and compared with the survey results. RESULTS:
      Eighty-four of 249 active members responded with 76 (31%) replies submitted for
      analysis. Specific serum tests were advocated by 41 of 76 (54%) respondents,
      although the majority (52 of 65 [80%]) felt that they were only "occasionally" or
      "never" necessary. The most common tests were rheumatoid factor (38%), Lyme titer
      (36%), erythrocyte sedimentation rate (34%), and antinuclear antibody (33%).
      Fifty-one of 71(72%) felt that computed tomography (CT) was "always" or "often"
      necessary and 50 of 72 (69%) replied that chest radiography (CXR) was "always" or
      "often" necessary. There was no significant difference between CT and CXR
      ordering (P < .51). In contrast, magnetic resonance imaging (MRI) was described
      as "always" or "often" necessary in 28 of 71 (39%) of the surveys, significantly
      less than CT (P < .0001). There was no statistical impact of practice
      specialization on ordering of serum tests (P = .25) or imaging (P = .50 for CT; P
      = .46 for CXR; P = .45 for MRI). Following analysis of 1,510 vocal fold paralysis
      abstracts, 19 publications were found to be appropriate for an EBM review of
      serum testing with 15 available for review of radiographic imaging. Only one
      study presented level III evidence; the remainder were levels IV and V comprised
      of retrospective series and case reports. The evidence supporting serum or
      radiographic testing toward the evaluation of idiopathic vocal fold paralysis is
      given an overall grade of "C." CONCLUSIONS: Serum and radiographic testing for
      the evaluation of vocal fold paralysis is supported by grade "C" evidence only.
      There are no existing prospective studies estimating the clinical impact of
      testing on diagnosis or patient outcome. Current practice, as estimated by a
      survey of the ABEA membership, is not well founded for serum testing and only by
      retrospective case series with regard to imaging. Further study into the nature
      of idiopathic vocal fold paralysis and outcomes assessment of diagnostic
      paradigms may improve clinical practice.

PMID- 16954977
TI  - Modern management of laryngotracheal stenosis.
AB  - OBJECTIVES: Laryngotracheal stenosis is a complex problem resulting most often
      from intubation, trauma,or autoimmune disease. Management options include
      dilation or airway reconstruction including laryngotracheoplasty (LTP),
      cricotracheal resection (CTR), and tracheal resection (TR). We describe our
      experience with management of this difficult problem. STUDY DESIGN: Retrospective
      chart review of patients treated for laryngotracheal stenosis between January
      1995 and July 2005 at an academic, tertiary referral center. METHODS: A total of
      127 patients were treated during the study period. Patients were followed, and
      hospital records were reviewed. RESULTS: There were 38 male and 89 female
      patients with an average age of 55.5 years treated for laryngotracheal stenosis
      resulting from intubation (64), idiopathic (25) or autoimmune disease (18),
      radiation (9), trauma (5), prior surgery (4), and relapsing polychondritis (2).
      Thirty-three percent were treated for grade I stenosis, 44% grade II, 19% grade
      III, and 4% grade IV. Seventy percent of patients undergoing initial dilation
      required a subsequent procedure. LTP, CTR, or TR was performed in 43%, 48%, 71%,
      and 100% of patients with grade I through IV stenosis, respectively. Among 76
      patients undergoing LTP, CTR, or TR, 24 (32%) required a subsequent intervention.
      Among 36 patients treated with primary LTP, CTR, or TR, only 10 (28%) required
      further therapy. Twenty-two of 35 (63%) tracheostomy-dependent patients were
      ultimately decannulated. Three patients died in the immediate postoperative
      period. CONCLUSIONS: Patients undergoing dilation for laryngotracheal stenosis
      require multiple procedures. However, major reconstructive procedures are well
      tolerated and currently represent a viable primary treatment for laryngotracheal
      stenosis.

PMID- 16954978
TI  - Methacholine challenge testing in the diagnosis of paradoxical vocal fold motion.
AB  - OBJECTIVE: The purpose of this study was to determine whether methacholine
      challenge testing (MCT) combined with serial laryngoscopy could elicit and
      visualize paradoxical vocal fold motion (PVFM) during asymptomatic periods and
      suggest laryngeal dysfunction as an etiology of episodic dyspnea. STUDY DESIGN: A
      retrospective study of seven adult patients. METHODS: Medical records of seven
      adult patients who were referred to an otolaryngology clinic with recurrent
      episodes of dyspnea or choking and underwent bronchoprovocation testing were
      reviewed. After initial fiberoptic laryngoscopy and pulmonary function testing
      (PFT), bronchoprovocation was performed using aerosolized methacholine at
      increasing concentrations. Each administration was followed by repeated
      laryngoscopy and PFT. A positive endoscopic test was marked by the visualization
      of paradoxical adduction of the true vocal folds during inspiration. A positive
      bronchoprovocation test was marked by a 20% or greater decline in the forced
      expiratory volume. RESULTS: All seven patients demonstrated normal upper airway
      anatomy and function on initial laryngoscopy. In three patients, a positive
      endoscopic examination demonstrating PVFM was elicited during MCT. In three, the
      bronchoprovocation test was positive, and asthma was diagnosed. In one patient,
      both tests were negative. PVFM was seen in all patients whose chief complaint was
      choking (n = 2) but in only one of five patients whose chief complaint was
      dyspnea. CONCLUSIONS: PVFM may be elicited and observed during MCT coupled with
      serial laryngoscopy. This test holds promise in differentiating vocal cord
      dysfunction from asthma during asymptomatic periods in patients who present with
      recurrent episodes of refractory dyspnea.

PMID- 16954979
TI  - The impact of endoscopic cultures on care in rhinosinusitis.
AB  - OBJECTIVES: The objectives of this retrospective, observational study were
      primarily to analyze endoscopically guided culture results (EGCRs) from an office
      setting in patients with subclassifications of chronic rhinosinusitis (CRS) and
      to determine the frequency EGCR-altered patient management; and secondarily to
      determine whether purulent secretions are more likely to be positive for a
      bacterial pathogen. METHODS: Consecutive symptomatic patients with nasal
      secretions not currently on antibiotics were cultured endoscopically. Patients
      were classified as chronic rhinosinusitis (CRS; n = 41) or acute exacerbation of
      chronic rhinosinusitis (AECRS; n = 27). Initial therapy was individualized and 32
      of 68 (47%) had an antibiotic initiated before availability of the EGCR. Patients
      were reassessed 2 to 4 days later, and therapy was continued or altered based on
      clinical course and EGCR. RESULTS: EGCRs were positive in 41 of 68 (60.2%) of all
      patients. Incidence of positive cultures was not statistically different between
      CRS (21 of 41 [51%]) and AECRS (20 of 27 [74%]) patients. Initial therapy was
      changed in 45 of 68 (66%) patients. In 35 of 68 (51.4%), the change was directed
      by EGCR; in 11 of 77 (14.2%), the change was unsubstantiated by EGCR, and in no
      cases was an antibiotic initiated inappropriate to EGCR. The frequency of
      pathogens in the subgroups of CRS and AECRS, respectively, were Staphylococcus
      aureus (9 of 41 [22%]; 9 of 27 [33%]), acute pathogens (6 of 41 [14.6%], 7 of 27
      [25.9%]), and Pseudomonas aeruginosa (5 of 41 [12%], 5 of 27 [18.5%]) and were
      not statistically different between subgroups. Purulent cultures were not
      significantly more likely to be Gram stain-positive than nonpurulent cultures (12
      of 34 [35%] compared with 6 of 34 [17.6%], respectively; P = .1). Purulent
      cultures were more likely to be culture-positive (25 of 34 [73.5%]) compared with
      nonpurulent secretions (17 of 34 [50%]; P < .05). AECRS was significantly more
      likely to be purulent (21 of 27 cases) compared with CRS (13 of 41 cases, P <
      .001). CONCLUSION: EGCR directed a change in therapy in 35 of 68 (51.4%) patients
      with CRS. The pathogens isolated from CRS and AECRS were similar and
      predominately S. aureus, acute pathogens, and P. aeruginosa. Purulent secretions
      are more frequently bacteriologically positive than nonpurulent secretions and
      more common in AECRS than CRS.

PMID- 16954980
TI  - Continuous intraoperative facial nerve monitoring in predicting postoperative
      injury during parotidectomy.
AB  - OBJECTIVES/HYPOTHESIS: To assess whether the use of continuous intraoperative
      facial nerve monitoring correlates to postoperative facial nerve injury during
      parotidectomy. STUDY DESIGN: A retrospective analysis. METHODS: Forty-five
      consecutive parotidectomies were performed using an electromyograph (EMG)-based
      intraoperative facial nerve monitor. Of those, 37 had complete data for analysis.
      Intraoperative findings and final interpretation of the EMGs were analyzed by a
      senior neurologist and neurophysiologist. All patients were analyzed, including
      those with preoperative weakness and facial nerve sacrifice. RESULTS: The overall
      incidence of facial paralysis (House-Brackmann scale > 1) was 43% for temporary
      and 22% for permanent deficits. This includes an 11% incidence of preoperative
      weakness and 14% with intraoperative sacrifice. An abnormal EMG occurred in only
      16% of cases and was not significantly associated with permanent or temporary
      facial nerve paralysis (chi, P < 1.0; Fisher's exact P < .68). Of the eight
      patients with permanent paralysis, only two had abnormalities on the facial nerve
      monitor. Also, only one of five patients with intraoperative sacrifice of the
      facial nerve had an abnormal EMG. Factors significantly associated with the
      incidence of facial paralysis include malignancy, advanced age, extent of
      parotidectomy, and dissection beyond the parotid gland (chi and Fisher's, P <
      .05). CONCLUSIONS: The results suggest that abnormalities on the intraoperative
      continuous facial nerve monitor during parotidectomy do not predict facial nerve
      injury. The incidence of permanent and temporary facial nerve paralysis compare
      favorably with the literature given that this study includes patients with
      revision surgery, intraoperative sacrifice, and preoperative paralysis. Standard
      of care implications will be discussed.

PMID- 16954981
TI  - Transnasal endoscopic surgery of the pituitary: modifications and results over 10
      years.
AB  - OBJECTIVE: A 10-year retrospective review of three endoscopic approaches used by
      the authors for pituitary gland surgery is presented. We review our results and
      complications and outline the advantages and disadvantages of each. The
      variations in nasal anatomy that factor in the endoscopic approach are tabulated
      and discussed. METHODS: A chart review and examination of computed tomography and
      magnetic resonance imaging scans of patients who have had endoscopic pituitary
      surgery by the authors was performed. We gathered specific details of the
      operative approach, nasal-sinus anatomy, tumor location, required ancillary nasal
      procedures, and postoperative complications. RESULTS: Ninety patients had
      endoscopic pituitary surgery. Operative reports and review of radiographic
      studies were possible for 75 patients. The surgical approach progressed over 10
      years from endoscopic transseptal (42) to bilateral transostial (13) to
      unilateral transostial (20). Adequate exposure for the degree of resection was
      achieved in all patients. Complications included hemorrhage requiring return to
      the operating room (1), transient visual field loss (2), and transient diabetes
      insipidus (7). Four patients subsequently had craniotomy to resect suprasellar
      tumor extension. The average follow-up was 6 years. One patient required revision
      endoscopic resection 3 years later for tumor recurrence. Anatomic findings
      included nasal septal deflections in 36 (48%) of the patients, abnormalities of
      the turbinates in 42 (56%), and variances of the sphenoid sinus septum in 59
      (79%) of the patients. In the unilateral transostial approach, the operative side
      was often determined by anatomic factors. CONCLUSION: The authors have
      exclusively used endoscopic surgery of pituitary gland tumors for over 10 years.
      Modifications to the approach have occurred as a result of increased surgeon
      experience and improved technology. The unilateral transostial approach is safe,
      effective, and recommended.

PMID- 16954982
TI  - Visually enhanced vestibulo-ocular reflex: a diagnostic tool for migraine
      vestibulopathy.
AB  - OBJECTIVES: 1) To compare the incidence of elevated visually enhanced vestibular
      ocular reflex (VVOR) rotational gain during rotational chair testing in a normal
      control group versus a group of patients diagnosed with migraine vestibulopathy;
      2) to discuss the possible application of VVOR gain during rotational chair
      testing for diagnosing migraine vestibulopathy. STUDY DESIGN: Prospective normal
      control group and retrospective cohort comparison. METHODS: 1) Prospective
      rotational chair studies including VVOR in 20 normal control patients; 2)
      retrospective review of vestibular studies including VVOR in 100 consecutive
      patients with migraine vestibulopathy. RESULTS: Twenty of the normal controls and
      69 of the migraine vestibulopathy patients met all inclusion criteria. One of 20
      (5%) normal control patients had elevated VVOR gain, whereas 49 of 69 (71%) of
      migraine vestibulopathy patients had elevated VVOR gain. CONCLUSIONS: VVOR gain
      normal criteria were appropriate in 95% of our normal control test group. VVOR
      gain was more frequently elevated in migraine vestibulopathy patients than in the
      normal controls, and the difference was significant (P < .001). VVOR gain
      elevation was the most common vestibular test abnormality in this cohort of
      patients with migraine vestibulopathy. Because VVOR measures visual-vestibular
      interaction and its central connections, this parameter may be a useful
      diagnostic tool for migraine vestibulopathy in patients manifesting
      disequilibrium and motion sensitivity.

PMID- 16954983
TI  - Vocal fold healing after laser cordectomy with adjuvant cryotherapy.
AB  - OBJECTIVES: To understand the effect of adjuvant cryotherapy on glottic wound
      healing after endoscopic CO2 laser cordectomy. STUDY DESIGN: Canine acute injury
      model with videolaryngostroboscopic and histopathologic outcomes analysis.
      METHODS: Twelve adult male dogs underwent bilateral endoscopic CO2 laser
      transmuscular cordectomy followed by randomized unilateral endoscopic glottic
      cryotherapy. The animals were randomly divided into four groups and underwent
      videolaryngostroboscopy followed by sacrifice at 0, 2, 6, and 12 weeks
      postoperatively. Three untreated male dogs served as controls. Histopathologic
      sections were prepared with Alcian blue, Giemsa, hematoxylin-eosin, movat's,
      Masson's trichrome, and picrosirius stains. RESULTS: Videostroboscopy
      demonstrated an earlier restoration of glottic volume and a return of mucosal
      waves among vocal folds treated with combined therapy by 6 weeks posttreatment.
      The mean depth of inflammatory reaction in the vocal cords treated with combined
      therapy was 1.07 mm versus 1.15 mm in vocal cords treated with CO2 laser therapy
      alone. At 2 and 6 weeks postoperatively, combined treatment was associated with a
      decreased volume of collagen. At 12 weeks postoperatively, combined treatment was
      associated with greater collagen organization, normalized collagen
      histoarchitecture, and decreased keratinization. CONCLUSIONS: Adjuvant
      cryotherapy appears to alter glottis-specific wound healing, leading to decreased
      and more organized collagen formation and decreased keratinization with a
      resultant improvement in glottic function, when compared with CO2 laser surgery
      alone, in an acute canine injury model. Studies in humans are ongoing to further
      evaluate the clinical potential of cryotherapy on glottic wound healing.

PMID- 16954984
TI  - Frontal sinus cranialization using the pericranial flap: an added layer of
      protection.
AB  - OBJECTIVES: Extensive fractures involving the anterior and posterior tables of
      the frontal sinus are treated by frontal sinus cranialization. During this
      procedure, the disrupted posterior wall of the frontal sinus is removed, the
      sinus mucosa is drilled away, and the brain and dura are permitted to rest
      against the repaired anterior wall and sinus floor. Conventionally, the area
      originally occupied by the frontal sinus is left as dead space or filled with
      free adipose tissue. We describe a method of cranialization using a pericranial
      flap and report our experience with this technique. STUDY DESIGN: Retrospective
      study. METHODS: The medical records of patients who underwent frontal sinus
      cranialization using the pericranial flap at our institution were reviewed.
      Demographics, indications for cranialization, complications, and perioperative
      outcomes were examined. RESULTS: A total of 19 patients underwent (bilateral)
      frontal sinus cranialization with the pericranial flap between 2000 and 2005.
      Indications included extensive frontal sinus fractures involving the posterior
      table (78.9%), mucocele (10.5%), arteriovenous malformation (5.3%), and frontal
      bone osteomyelitis (5.3%). There were no intraoperative complications. A
      postoperative cerebrospinal fluid leak occurred in one patient with extensive
      skull base injuries. This was repaired endoscopically. Follow-up ranged from 9 to
      55 months. CONCLUSIONS: The pericranial flap is easily harvested and versatile.
      Using this vascularized tissue during cranialization affords added protection by
      providing an extra barrier between the intracranial cavity and the frontal bone
      and sinonasal tract. This technique is inexpensive, safe, and effective and
      should be considered when cranialization of the frontal sinus is performed.

PMID- 16954985
TI  - Quality of life in advanced oropharyngeal carcinoma after chemoradiation versus
      surgery and radiation.
AB  - OBJECTIVE: The objective of this cohort study from a tertiary academic university
      practice was to identify differences in patients' perceived quality of life after
      either chemoradiation or surgery and radiation for advanced-stage oropharyngeal
      carcinoma. METHODS: From institutional databases, thirty-five patients were
      identified who had undergone either primary chemoradiation or primary surgery and
      postoperative radiation for advanced oropharyngeal cancer (stage II-IV). Patients
      voluntarily responded by mail using the University of Washington quality-of-life
      instrument version 4 (UW-QOL). Data were analyzed using chi and Wilcoxon tests.
      RESULTS: There were 17 patients who underwent chemoradiation and 18 patients who
      underwent surgery and postoperative radiation. All surgical patients had
      undergone free-flap reconstruction. Patients completed the UW-QOL an average of
      25 months after treatment. There was no statistically significant difference
      between the two groups with regard to any specific domain, including pain,
      appearance, swallowing, chewing, speech, saliva, or mood. There was a trend
      toward significance for taste (P = .07) with chemoradiation patients reporting
      poorer taste function. The lack of difference in the patients' perception of
      appearance and swallowing was rather surprising given the vastly different
      treatment modalities. Respondents reported equivalent overall quality of life in
      response to global quality-of-life questions. CONCLUSION: Most patients with
      advanced oropharyngeal carcinoma report good quality of life after treatment,
      regardless of treatment modality. Although the short-term side effects of
      treatment may be different between the groups, long-term quality of life is
      remarkably similar whether the patients choose primary chemoradiation or surgery
      with postoperative radiation.

PMID- 16954986
TI  - Lateral tympanoplasty for total or near-total perforation: prognostic factors.
AB  - OBJECTIVE: To identify prognostic factors affecting outcome in lateral
      tympanoplasty for total or near-total tympanic membrane perforation. STUDY
      DESIGN: Retrospective case series. METHODS: Patients were those presenting with
      total or near-total tympanic membrane perforation undergoing lateral
      tympanoplasty from 1999 to 2004. We systematically collected demographic,
      clinical, audiologic, and outcome information. Student t test was used to
      determine group differences. Logistic regression analysis was used to examine the
      relationship between success of grafting (dependent variable) and the independent
      variables. Multiple regression analysis was used to examine the relationship
      between postoperative air-bone gap (ABG) and independent variables. RESULTS:
      There were seventy-seven cases (58 primary and 19 revision cases) with average
      follow-up of 17 months. Successful tympanic membrane grafting occurred in 91% of
      cases. None of the independent variables studied was predictive of the success of
      graft incorporation (P > .05). The mean preoperative ABG was 29.8 +/- 10 dB and
      improved to a postoperative ABG of 16.5 +/- 11 dB (P < .001). Smaller
      preoperative ABG and normal malleus handle were associated with smaller
      postoperative ABG. In revision cases, mastoidectomy was associated with better
      functional results. CONCLUSIONS: Successful grafting of near-total and total
      tympanic membrane perforations occurred in 91% of the cases and was independent
      of demographic, disease, and technical variables. Disease variables (preoperative
      ABG and status of malleus handle) had a greater prognostic value on postoperative
      ABG than other variables. In revision tympanoplasty, mastoidectomy is associated
      with a better functional outcome.

PMID- 16954987
TI  - Organotypic (raft) culture of biopsy-derived upper respiratory epithelium.
AB  - OBJECTIVE: The objective of this study was to derive a reliable technique for
      culturing biopsy-derived upper respiratory epithelium in a system that supports
      epithelial differentiation and simulates the normal epithelial life cycle. STUDY
      DESIGN: The authors conducted a prospective study of modification and development
      of an in vitro tissue culture method. METHODS: Thirty biopsy specimens from 16
      individuals with recurrent respiratory papillomatosis and chronic tonsillitis,
      pretreated to prevent bacterial and fungal overgrowth, were digested with trypsin
      to create a supernatant of individual cells. The cells were plated and incubated.
      At 14 to 16 days, the resulting colonies were placed on a wire cloth raft and fed
      through diffusion from the underlying culture medium in an air-liquid interface.
      RESULTS: Eight specimens were successfully cultured for an average of over 32
      days. The longest duration of sustained growth was 60 days. Low-risk human
      papillomavirus specimen-based cultures reproduced infection in cultured squamous
      epithelium with corresponding histopathologic features indicating a high level of
      stratification and differentiation. CONCLUSIONS: Unlike commercially available
      cell lines, biopsy-derived material is predisposed to contamination, and
      successful in vitro culture and experimentation creates many unique challenges.
      An organotypic culture system, capable of reproducing the differentiation
      dependent replication cycle of human papillomavirus, may be used for culturing
      biopsy-derived specimens for a variety of studies.

PMID- 16954988
TI  - Surgical treatment of pediatric cholesteatomas.
AB  - OBJECTIVE: : Management of pediatric cholesteatomas remains controversial. We
      reviewed our 16-year experience in the surgical treatment of cholesteatomas in
      children and describe a treatment paradigm. STUDY DESIGN: : The authors conducted
      a retrospective review. METHODS: : A total of 106 mastoidectomies (86 for an
      acquired cholesteatoma and 20 for a congenital cholesteatoma) were performed in
      children 16 years old and younger from 1988 to 2003. Follow up ranged from 2
      years to 12 years with a mean follow-up period of 6 years. Hearing outcomes,
      cholesteatoma recidivism, and dry mastoid cavity were the main outcomes measured.
      RESULTS: : Seven (7%) patients had revision surgery for cholesteatoma recidivism.
      Rates of cholesteatoma recurrence for canal all up (CWU) and canal wall down
      (CWD) mastoidectomy groups were similar (8% vs. 6%). The percentage of patient
      with good serviceable hearing (pure-tone average </=25 dB) was higher in those
      with a CWU mastoidectomy as compared with the CWD mastoidectomy group (81% vs.
      47%) (P < .05). Extent of disease and stapes superstructure erosion on
      presentation were significant (P < .05) predictors of both cholesteatoma
      recidivism and poor hearing. All 106 subjects studied had a dry mastoid and 78
      patients (74%) had a maintenance-free cavity at the time the study was completed.
      CONCLUSION: : The treatment of pediatric cholesteatomas should be individualized
      with CWD mastoidectomy chosen for patients with recurrent or more extensive
      disease. We conclude that the CWU procedure is an adequate surgical option for
      treating most acquired and congenital cholesteatomas, preventing disease
      recurrence, and maintaining good hearing outcomes.

PMID- 16954989
TI  - The endoscopic management of Zenker diverticulum: CO2 laser versus endoscopic
      stapling.
AB  - OBJECTIVE: The purpose of this project was to analyze the endoscopic management
      of Zenker diverticulum (ZD) using both the CO2 laser and endoscopic stapling
      techniques. This study compares the two techniques in terms of diverticulum size,
      onset to oral intake, hospital stay, resolution of symptoms (dysphagia and
      regurgitation), and complications. STUDY DESIGN: A retrospective consecutive case
      series was performed at an academic medical center. METHODS: Forty patients
      underwent an attempted endoscopic resection of the ZD using either the CO2 laser
      or the endoscopic stapling technique. The two techniques were compared on a
      variety of parameters, including diverticulum size, hospital stay, onset to oral
      intake, resolution of symptoms, and complications. Symptom scores were obtained
      before and after surgery with a patient self-reported scoring report (scale 0-3
      for both dysphagia and regurgitation with 0 indicating asymptomatic and 3 severe
      symptoms). RESULTS: Forty patients underwent an attempted endoscopic management
      of ZD. Five patients (12.5%) failed endoscopic exposure (four converted to open,
      one observed). Sixteen patients underwent CO2 laser management and 19 underwent
      endoscopic stapling. The mean diverticulum size (3.8 cm CO2 laser versus 4.4 cm
      stapling) was not significantly different for the two groups. Both groups
      demonstrated a significant decrease in preoperative versus postoperative
      dysphagia and regurgitation symptoms scores, respectively, CO2 laser dysphagia
      scores decreasing from 2.75 to 1.38 and the regurgitation score dropping from
      1.51 to 0.68, whereas endoscopic stapling dysphagia score decreased from 2.74 to
      1.21 and the regurgitation score dropped from 1.37 to 0.53. Overall, 86% of
      patients demonstrated an onset of liquid intake on postoperative day 1 and the
      average length of stay was 3.4 days in the CO2 laser group and 1.5 days in the
      endoscopic stapling (P < .0015). Complications included dental trauma in four
      patients (two CO2 laser and two stapling) and subcutaneous air in three patients
      (all three CO2 laser). There were no cases of mediastinitis, recurrent laryngeal
      nerve injury, fistula, or perioperative death. CONCLUSIONS: The endoscopic
      management of ZD is a safe and effective technique. The endoscopic stapling
      technique appears to have an improved efficacy and safety when compared with the
      CO2 laser technique. The two techniques are compared and contrasted.

PMID- 16954990
TI  - Long-term comparison between submucosal cauterization and powered reduction of
      the inferior turbinates.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the results of powered turbinoplasty and to
      compare these with submucosal cauterization of the inferior turbinates. STUDY
      DESIGN: Prospective, randomized, comparative surgical trial. METHODS: Nineteen
      patients with medication-resistant chronic nasal obstruction caused by inferior
      turbinate hypertrophy were randomized to undergo powered turbinoplasty on one
      side and submucosal cauterization on the other. For each side, an extensive
      assessment (symptom scoring, endoscopic scoring, and acoustic rhinometry) was
      recorded preoperatively and on week 1, week 3, month 3, year 1, and year 5
      postoperatively. RESULTS: Powered turbinoplasty was superior to submucosal
      cauterization on all aspects of the assessment. A significant difference (P <
      .05) was noted for postoperative crusting, endoscopical scoring of turbinate
      size, and acoustic rhinometry measurements of nasal cavity volume and mean area
      at the level of the nasal valve. In addition, the results of powered
      turbinoplasty were still apparent on long term follow-up, whereas submucosal
      cauterization was associated with a recurrence of turbinate hypertrophy.
      CONCLUSION: Performing a powered turbinoplasty leads to decreased patient
      morbidity during the postoperative healing and to a better control of long-term
      results when compared with submucosal cauterization.

PMID- 16954991
TI  - Radiographic and histologic analysis of the bone underlying inverted papillomas.
AB  - INTRODUCTION: Inverted papilloma (IP) is a benign but locally aggressive
      sinonasal tumor. Those localized to the maxillary sinus or medial maxillary wall
      have classically been removed through an external approach. In recent years,
      endoscopic removal has been advocated as an effective, minimally invasive
      approach. Successful endoscopic management is based on accurate intraoperative
      identification and complete resection of the tumor. The surgical management of
      the bone underlying the surface of an IP is less clearcut. Controversy exists as
      to whether the bony undersurface of an IP should be removed. In this article,
      histopathologic specimens and preoperative radiologic studies are prospectively
      examined to better understand the involvement of the bone underlying an inverted
      papilloma. MATERIALS AND METHODS: A prospective study of patients with maxillary
      sinus IP treated with endoscopic or endoscopic-assisted resection over a 12-month
      period was conducted. Intraoperatively, the site of tumor attachment was
      identified, and a 1- to 2-cm wedge of bone with overlying tumor was removed en
      bloc and analyzed under light microscopy. Preoperative radiographic studies were
      analyzed with respect to bony changes in the area of the tumor pedicle. RESULTS:
      On histopathologic analysis, the bony surface underlying the IP was irregular
      with multiple bony crevices in all nine cases. In two cases (22% of specimens),
      an isolated rest of normal-appearingsalivary gland and/or mucosal tissue was seen
      embedded in the underlying bone. Radiographic osteitic bony changes were seen at
      site of tumor attachment in 100% of cases. CONCLUSION: The irregularity of the
      bony surface may hinder complete tumor removal because microscopic rests of
      mucosa can be hidden within the bony crevices. Intraoperative removal of the bony
      surface at the site of tumor attachment may ensure a more complete removal.

PMID- 16954992
TI  - General and rhinosinusitis-related quality of life in patients with Wegener's
      granulomatosis.
AB  - OBJECTIVES: The objectives of this cross-sectional study were to outline the
      pattern of sinonasal morbidity and determine its effects on the quality of life
      (QOL) of patients with Wegener's granulomatosis (WG). METHODS: The authors
      conducted a survey of 199 patients with WG, including two validated (QOL)
      instruments to assess general (SF-36) and rhinosinusitis-specific quality of life
      (Sinonasal Outcome Test [SNOT-22]). RESULTS: Patients with WG who have sinonasal
      involvement reported significantly lower general QOL scores than their unaffected
      counterparts (P = .000006-0.04) for all SF-36 subsets except for emotional role.
      WG-related sinonasal morbidity was comparable to the high levels previously
      demonstrated in the general rhinosinusitis population. A total of 38.2% of all
      patients with WG reported a nasal symptom as their most troublesome from a list
      of nasal and constitutional symptoms. Twenty-three percent of all patients with
      WG rated nasal crusting and 17% rated epistaxis as one of their top three most
      troublesome symptoms even in the setting of multisystem disease. The inclusion of
      crusting, bleeding, and nasal deformity in the SNOT scoring significantly
      increased average scores of patients with WG (P = .024, paired t test).
      CONCLUSIONS: Sinonasal involvement impacts significantly on the general QOL of
      patients with WG and is at least as significant as that of the general
      rhinosinusitis population. Nasal symptoms that are of particular relevance to
      this patient group include nasal crusting and epistaxis.

PMID- 16954993
TI  - Diagnosis and management of skull base osteoradionecrosis after radiotherapy for
      nasopharyngeal carcinoma.
AB  - OBJECTIVE: The objective of this study was to investigate the diagnosis and
      management of skull base osteoradionecrosis (ORN) after radiotherapy for
      nasopharyngeal carcinoma (NPC). METHODS: The general information, clinical
      manifestations, and treatment outcomes were retrospectively evaluated in 15
      patients with skull base ORN after radiotherapy for NPC. RESULTS: The common
      symptoms of skull base ORN included foul odor, headache, and epistaxis.
      Endoscopic examination showed exposed bone or sequestration in the nasopharynx.
      The characteristic findings according to computed tomography included the
      following: bone was destroyed extensively and symmetrically or regionally; bone
      was exposed to the air cavity; sequestration can be observed; and small air
      bladder was present in the parenchyma. There were nine patients regional skull
      base ORN receiving surgery, two of whom died of postradiation temporal lobe
      necrosis and seven of whom survived for 2 to 7 years. Conservative treatments
      were provided to six patients, including five patients with extensive skull base
      ORN and one patient with regional ORN, among which three patients died of
      nasopharyngeal bleeding, one patient died of exhaustion, and two patients
      survived for 3 to 5 years. CONCLUSIONS: Clinical diagnosis of skull base ORN was
      based on symptoms, computed tomography, or magnetic resonance imaging and
      endoscopy. The final confirmation was according to pathologic examination.
      Surgery had the best effect. Extensive ORN accompanied by radiation brain damage
      or cranial nerves damage had poor prognosis. Nasopharyngeal bleeding and
      exhaustion were the main causes of death.

PMID- 16954994
TI  - Is lack of placement of drains after thyroidectomy with central neck dissection
      safe? A prospective, randomized study.
AB  - OBJECTIVE: Selective use of drains after thyroidectomy has been suggested in the
      literature. Although the safety of thyroidectomy without drains has been
      reviewed, there is little specific data available to identify the safety of
      thyroidectomy combined with central neck dissection (CND) without drains. This
      study aims to determine the feasibility and safety of thyroidectomy without
      drains, especially in cases of combined CND. STUDY DESIGN: Prospective,
      randomized study. MATERIALS AND METHODS: One hundred ninety-eight consecutive
      thyroidectomized patients were enrolled in this study. Drain group (n = 101)
      consisted of 41 hemithyroidectomies (HT), 28 total thyroidectomies (TT), and 32
      total TT with CND. No-drain group (n = 97) consisted of 42 HT, 18 TT, and 37 TT
      with CND. The following variables were examined: perioperative complications
      (hemorrhage, hematoma, seroma), intraoperative bleeding, operation time, volume
      of resected thyroid gland, time of hospital discharge after operation, duration
      of drain placement, and total amount of drainage (drain group). RESULTS: There
      were no significant differences in age, sex, volume of resected thyroid gland,
      types of operation, operation time, and histopathlologic diagnosis between two
      groups. In the drain group, overall perioperative complications occurred in seven
      (7/101, 6.9%) patients. In the no-drain group, overall perioperative
      complications occurred in nine (10/97, 10.3%) patients. There was no significant
      difference in overall perioperative complications between the drain and no-drain
      groups, even in cases of performing CND. Time of hospital discharge after
      operation was significantly shorter in the no-drain group than the drain group (P
      < .05). CONCLUSIONS: We conclude that thyroidectomy without drains is safe and
      effective even in combination with CND and appears to confer several advantages
      over the routine drainage method. In addition, we achieved significant reduction
      of hospital stay, which led to a reduction in costs for the patients.

PMID- 16954999
TI  - Immediate recurrent laryngeal nerve reconstruction and vocal outcome.
AB  - OBJECTIVE: The objective of this prospective study was to assess the long-term
      effects of immediate reconstruction of the recurrent laryngeal nerve (RLN) during
      thyroid cancer extirpation on postoperative phonatory function. SUBJECTS AND
      METHODS: The subjects were 22 patients with advanced thyroid cancer who underwent
      resection of the primary lesion and involved RLN. RLN paralysis was seen in 12
      patients preoperatively and involvement of the RLN was noted intraoperatively in
      10. Immediate reconstruction of the RLN was performed on eight patients using the
      great auricular nerve and one underwent direct anastomosis of the RLN stumps
      (group I). Nine patients opted not to have phonosurgical procedures (group II).
      The remaining four had arytenoid adduction immediately after cancer extirpation
      (group III). Phonatory function (stroboscopy, maximum phonation time [MPT], mean
      airflow rate [MFR], harmonics-to-noise ratio [HNR], jitter, and shimmer) was
      followed for at least 9 months. RESULTS: Minimal or no glottal gap during
      phonation was observed in six patients in group I, whereas the patients in group
      II had a large gap along the entire fold. HNR, MPT, and MFR were significantly
      better in group I (17.7 +/- 3.6 dB, 15.1 +/- 6.3 s, and 100 +/- 32 mL/s,
      respectively) than in group II (12.1 +/- 2.9 dB, 5.4 +/- 3.1 s, and 430 +/- 207
      mL/s, respectively). Patients in group III had a gap of varying degrees along the
      membranous fold. Although HNR, shimmer, and MPT in group III were comparable to
      group I, the other parameters were less favorable than in group I. CONCLUSION:
      Immediate RLN reconstruction at the time of thyroid cancer extirpation can
      provide excellent postoperative phonatory function.

PMID- 16954995
TI  - In vivo detection of head and neck cancer orthotopic xenografts by
      immunofluorescence.
AB  - PURPOSE: To determine whether Cy5.5-labeled antiepidermal growth factor (EGFR)
      antibody could be used to detect head and neck squamous cell carcinoma (HNSCC)
      xenografts in vivo. METHODS: AntiEGFR antibody (cetuximab) was labeled with
      Cy5.5, a fluorophore with emission in the near infrared range. The cetuximab
      Cy5.5 conjugate was systemically administered in subtherapeutic doses (50 microg)
      to mice bearing orthotopically xenografted HNSCC cell lines (SCC1, CAL27, and
      FaDu). As a control, isotype-matched human immunoglobulin (Ig)G1k antibody
      labeled with Cy5.5 was systemically injected in parallel experiments. All tumor
      regions (n = 6) were imaged by fluorescent stereomicroscopy at 0, 6, 24, 48, or
      72 hours. Tumor size was measured by high-frequency ultrasonography at 72 hours.
      Transcervical partial and near-total resections were then performed with
      stereomicroscopic imaging after each resection. The mandible and associated
      structures were then resected, paraffin embedded, and then serial sectioned for
      analysis. RESULTS: Tumors could be clearly visualized by near infrared
      fluorescent stereomicroscopy at 48 and 72 hours after systemic administration of
      cetuximab-Cy5.5 but not after administration with the labeled isotype control
      antibody, IgG1k-Cy5.5. Ultrasound measurement of tumors (n = 5) correlated with
      fluorescent measurements of tumor (Spearman's coefficient, 0.92, P </= .01). When
      fluorescent stereomicroscopic findings were correlated with histologic findings
      in near-total resections, this technique could accurately identify residual tumor
      less than 1 mm in size. CONCLUSION: Fluorescent immunoguided neoplasm detection
      may be used as a diagnostic tool and to guide surgical therapy by providing real
      time imaging information about the extent of disease or the presence of residual
      disease.

PMID- 16955002
TI  - How can an underlaid fascia graft form the middle layer of a reconstructed
      tympanic membrane?
AB  - OBJECTIVE/HYPOTHESIS: Autogenous fascia is a material popularly applied as a
      connective tissue graft for reconstruction of the tympanic membrane. The
      objective was to establish how an underlaid fascia graft can form the middle
      layer of a reconstructed tympanic membrane. STUDY DESIGN: In the underlaid
      technique, the graft is laid on the medial surface of the tympanic remnant
      without removal of the mucous membrane, which is covered with entodermal
      epithelium. Interestingly earlier authors have regarded this fact as natural,
      though, if it is really so, it must be a result of an unexpected, special
      mechanism that apparently contradicts the general rules of transplantation.
      METHODS: Experimental operations were performed on one ear of 114 adult, male
      guinea pigs. The posterior quadrants of the tympanic membrane were removed, and
      the perforation was closed with an underlaid temporal fascia graft. Examinations
      were made after different survival times. The temporal bones were removed
      immediately, and specimens were processed histologically. RESULTS: The graft
      proved to be well adapted to the margin of the tympanic membrane. The epithelium
      of the outer surface grew both from the meatal skin and from the margin of the
      tympanic remnant. In connection with the regeneration of the mucous membrane of
      the inner surface, unexpected, special events were observed. The originally
      intact epithelium of the mucous membrane was annihilated, and disappeared
      completely. Consequently, the fibrous layer of the tympanic remnant and the graft
      came into direct contact and grew together. The regeneration of the mucous
      membrane started at the margin of the graft. CONCLUSIONS: The histologic
      observations described have clarified the problem of the underlaid technique.

PMID- 16955001
TI  - Reconstruction of dorsal and/or caudal nasal septum deformities with septal
      battens or by septal replacement: an overview and comparison of techniques.
AB  - OBJECTIVES: The objectives of this study were to describe and compare two
      techniques used to correct nasal septum deviations located in the dorsal and/or
      caudal septum. STUDY DESIGN: The authors conducted a retrospective clinical chart
      review. METHODS: The authors conducted a comparison of functional and technical
      results between surgery in the L-strut of the septum in 114 patients with septal
      battens or by septal replacement by subjective self-evaluation and by examination
      of the position of the septum during follow up. RESULTS: There was subjective
      improvement in nasal breathing in 86% of the septal batten group and in 94% of
      the septal replacement group. This difference was not statistically significant.
      The technical result was judged by examining the position of the septum during
      follow up as midline, slightly deviated, or severely deviated. The septum was
      significantly more often located in the midline during follow up in the septal
      replacement group than in the septal batten group. CONCLUSION: Treatment of
      deformities located in the structurally important L-strut of the septum may be
      technically challenging and many functional, structural, and esthetic
      considerations must be taken into account. On the basis of this series, both
      septal battens and septal replacement techniques may be considered for correction
      of deviations in this area. The functional improvement rates were not
      significantly different between the techniques, although during follow up, the
      septum appeared to be significantly more often located in the midline in the
      septal replacement group. The techniques are described and their respective
      advantages and potential drawbacks are discussed.

PMID- 16954996
TI  - Effect of inhibitor of tumor necrosis factor-alpha and oxatomide on immune
      mediated otitis media.
AB  - OBJECTIVE: Inflammatory mediators (IMs) play a major role in the production of
      middle ear effusion (MEE). Tumor necrosis factor (TNF)-alpha and leukotrienes
      (LTs) appear to be important in the pathogenesis of otitis media with effusion
      (OME). The purpose of this study is to determine the effect of TNF-alpha and LT
      antagonist on the outcome of experimental immune-mediated OME. STUDY DESIGN:
      Prospective. METHODS: Otitis media was induced in rats by injecting keyhole
      limpet hemocyanin (KLH) transtympanically 7 days after systemic immunization.
      Experimental groups were treated with soluble TNF receptor type I (sTNF RI) or
      oxatomide simultaneously. Seventy-two hours after transtympanic injection, MEE
      was aspirated, and temporal bone was taken. Vascular permeability (VP) of the
      middle ear mucosa was measured using the Evans blue dye technique. Hematoxylin
      eosin stain and immunohistochemical stain for leukocyte common antigen was
      performed. RESULTS: In KLH, sTNF RI, and oxatomide groups, MEE was developed in
      83%, 0%, and 66% of the ears, respectively. The sTNF RI group showed significant
      decrease in effusion production, inflammation, mucosal thickening, and VP
      compared with the KLH group. These parameters were less significant in the
      oxatomide group than in the sTNF RI group. CONCLUSION: Transtympanic
      administration of sTNF RI and oxatomide appears to suppress the development of
      immune-mediated MEE.

PMID- 16955000
TI  - Development and validation of the vocal tremor scoring system.
AB  - BACKGROUND: Essential tremor (ET) occurs in approximately 4% of the population,
      and 25% of patients with ET have vocal tract involvement referred to as essential
      tremor of voice (ETV). Treatment of vocal tremor has a variable success rate most
      likely as a result of inaccurate identification of the affected area(s). A vocal
      tremor assessment system was developed to standardize the evaluation and scaling
      of vocal tremor. Applying this system clinically can help determine who will
      benefit most from botulinum toxin injection treatment. The Vocal Tremor Scoring
      System (VTSS) can also be used as a tool to determine treatment efficiency for
      all treatment modalities of ETV, including surgery, medications, and implantable
      devices. STUDY DESIGN: The authors studied instrument development and validation.
      METHODS: A clinical consensus conference was conducted to develop an assessment
      tool for standardized rating of vocal tremor location and severity. The
      assessment tool was then tested for reliability using video-perceptual analysis.
      Once validated, the assessment tool was applied to 10 examinations of patients
      with vocal tremor who had been treated with botulinum toxin A (BtxA) injections
      of the thyroarytenoid muscle(s) to determine the ability of the scoring
      instrument to predict treatment outcome. RESULTS: : The VTSS is based on severity
      scores for different anatomic sites within the vocal tract. The assessment areas
      of the VTSS are the palate, base of tongue, pharyngeal walls, larynx,
      supraglottis, and true vocal cords. Statistical analysis of the video-perceptual
      analysis results showed that the anatomic sites with the best interrater
      agreement were the true vocal folds, palate, base of tongue, and supraglottis.
      Overall, the VTSS demonstrated a level of interrater reliability of at least
      0.914 at all sites. Intrarater reliability was excellent. The consensus group
      also analyzed 10 standardized examinations and the scores from both reviewer
      groups were then compared and found to have a reliability of at least 0.6 at each
      site. Pretreatment VTSS scores of 10 patients with ETV who underwent BtxA therapy
      were then compared with treatment response. The VTSS predicted the favorable
      treatment outcome 100% of the time when the score given to the true vocal folds
      was equal or greater to the mean of the scores given to the other sites.
      CONCLUSION: The VTSS represents the first standardized system for rating anatomic
      site(s) and severity of vocal tremor. This tool will allow improved communication
      between otolaryngologists, facilitate research in vocal tremor treatments, and
      establish a descriptive system for assessing vocal tremor. Using this assessment
      tool for patients with vocal tremor increases optimal patient selection and
      success rate for intralaryngeal botulinum toxin treatment.

PMID- 16954997
TI  - Glucocorticoids inhibit diastrophic dysplasia sulfate transporter activity in
      otosclerosis by interleukin-6.
AB  - HYPOTHESIS/OBJECTIVE: Otosclerosis is a bone remodeling disorder localized to the
      otic capsule and associated with inflammation. In vitro, increased activity of
      the diastrophic dysplasia sulfate transporter (DTDST), which is implicated in
      bone metabolism, has been reported. Because glucocorticoids modulate the bone
      turnover and inhibit inflammatory processes, we investigated the effect of
      dexamethasone (Dex) on interleukin-6 and DTDST in otosclerosis. STUDY DESIGN: The
      authors conducted a prospective, case-control study. MATERIALS AND METHODS:
      Primary cell cultures were obtained from stapes and external auditory canals in
      otosclerosis (n = 21) and control patients (n = 18). Assays with [H]Dex evaluated
      specific binding sites in otosclerotic and control stapes. The effects of Dex (10
      to 10 M) and RU486 (10 M), a glucocorticoid antagonist, were studied on DTDST
      activity by sulfate uptake. IL-6 secretion was measured in culture media before
      and after Dex (10 M, 24 hours). The effect of IL-6 (10 M, 24 hours) was assessed
      on DTDST activity in control stapes. RESULTS: : The number of specific Dex
      binding sites was similar in all stapedial cultures. Dex inhibited DTDST activity
      (19.4 +/- 1.02 vs. 29.4 +/- 3.94 pmol/microg prot/5 minutes) only in otosclerotic
      stapes. This effect was dose-dependent, antagonized by RU 486 and only observed
      24 hours after Dex exposure. Interleukin (IL)-6 stimulated DTDST activity in
      normal stapes, whereas Dex inhibited IL-6 production only in otosclerotic stapes.
      CONCLUSION: Dex inhibits the DTDST activity, at least in part, through a
      reduction of IL-6 secretion only in otosclerotic cells. This effect is mediated
      through the glucocorticoid receptors and may lead to the reduction of bone
      turnover.

PMID- 16955003
TI  - Posterior cranial fossa tumors in young adults.
AB  - OBJECTIVE/HYPOTHESIS: This retrospective study presents our experience on the
      posterior cranial fossa tumors in young adults during the past 15 years. METHODS:
      From 1991 to 2005, 16 (0.8%) of 2,091 young adults (range, 16-29 years) with
      dizziness/vertigo, hearing loss, or tinnitus were diagnosed with posterior fossa
      tumor. Each patient underwent a battery of audiovestibular tests and image study.
      RESULTS: Audiometry revealed sensorineural hearing loss in 12 patients (75%).
      Spontaneous nystagmus was disclosed in eight patients (50%), consisting of
      bilateral gaze nystagmus in five, unilateral gaze nystagmus in two, and downbeat
      nystagmus in one. Electronystagmographic examination displayed abnormal eye
      tracking test in 75% and abnormal optokinetic nystagmus test in 81% of cases.
      Magnetic resonance imaging scan demonstrated space-occupying lesions at the
      cerebellopontine angle in 11, cerebellum in two, brainstem in two, and jugular
      fossa in one. Diagnoses consisted of vestibular schwannoma and neurofibromatosis
      II in eight patients (50%), glial neoplasm (including astrocytoma, ependymoma,
      glioma) in four patients (25%), epidermoid cyst in three patients, and glomus
      jugulare tumor in one patient. At study close, excluding one lost patient, three
      patients died as a result of recurrent or residual tumor at the primary site.
      Restated, 12 of 15 (80%) patients were alive. CONCLUSIONS: Unlike predominant
      medulloblastoma in children, the most frequent posterior fossa tumor in young
      adults is vestibular schwannoma and neurofibroma. However, the second most
      frequent one in young adults is glial neoplasm as opposed to meningioma in
      adults.

PMID- 16955004
TI  - Cervical metastasis from squamous cell carcinoma of the maxillary alveolus and
      hard palate.
AB  - OBJECTIVES: Squamous cell carcinoma has a predilection for regional lymphatic
      metastasis. The occurrence of occult cervical metastases from squamous cell
      carcinoma of the hard palate and maxillary alveolar ridge has not been studied
      systematically. We have observed many patients who have returned after resection
      of a primary cancer in these sites with a delayed cervical metastasis. Some of
      these patients have died of regional or distant metastasis despite control of
      their primary cancer. METHODS: We have studied 26 patients with squamous cell
      carcinoma of the maxillary alveolar ridge and hard palate to define incidence of
      cervical metastasis. RESULTS: Overall incidence of cervical metastasis was:
      clinical 2 of 26 (7.6%) and occult 7 of 26 (27%) for a total of 9 of 26 (34.6%).
      The 5-year disease-specific survival was 13 of 22 (59%). Surgery for regional
      failure was successful in 66% (6 of 9). Radiation was administered after surgery
      in eight of nine patients. CONCLUSION: Cervical metastasis from cancer of the
      palate and alveolar ridge is significant. Regional surgery for recurrent disease
      usually requires radical or modified radical neck dissection. Selective elective
      neck dissection should be offered to patients with cancer of the hard palate and
      alveolar ridge. It affords the patient and the treatment team valuable histologic
      information, which may help to guide therapy and reduce the potential need for
      future hospitalization, chemoradiation, and more radical surgery.

PMID- 16954998
TI  - Does induction chemotherapy still have a role in larynx preservation strategies?
      The experience of Institut Catala d'Oncologia in stage III larynx carcinoma.
AB  - BACKGROUND: Radiotherapy with concurrent cisplatin is the standard alternative to
      total laryngectomy for patients with locally advanced laryngeal cancer. The value
      of induction chemotherapy in larynx-preservation therapies remains unknown.
      Hyperfractionation radiotherapy might improve disease-free survival. METHODS:
      From August 1993 to August 2004, 71 patients with T3N0-1 larynx tumors and
      eligible for total laryngectomy received induction chemotherapy with three cycles
      of cisplatin plus fluorouracil. Clinical tumor response was assessed by indirect
      laryngoscopy and computed tomography scan. Patients with complete response
      received hyperfractionation radiotherapy, whereas those without complete response
      were proposed for total laryngectomy. RESULTS: A total of 71 consecutive patients
      were included. Thirty-three patients achieved complete response to induction
      chemotherapy (46.5%), four of them presented a tumor relapse, and all underwent
      salvage surgery. Seventy-six percent of surviving patients preserved a functional
      larynx. Despite not achieving complete response, 15 patients refused total
      laryngectomy and received hyperfractionation radiotherapy. Seven patients
      presented a tumor relapse and salvage surgery was performed in three of them.
      Fifty percent of surviving patients preserved a functional larynx. Twenty-two
      patients without complete response underwent total laryngectomy; three of them
      presented a tumor relapse but none could be rescued. With a median follow up of
      68 months, 5 five-year overall survival, 5-year disease-free survival, and 5-year
      larynx function preservation survival rates were 68% (confidence interval [CI],
      57-80), 75% (CI, 64-87), and 42% (CI, 29-54), respectively. No differences in
      overall survival were observed between groups. Five-year disease-free survival of
      patients without complete response who received hyperfractionation radiotherapy
      was significantly lower than that of the other two groups (P < .02). Ten patients
      with larynx preservation and no tumor relapse had chronic toxicity that caused
      the loss of larynx function: seven patients required permanent tracheotomy, two
      died from pneumonia, and one patient died as a result of a laryngeal necrosis.
      CONCLUSIONS: Patients with complete response to induction chemotherapy in
      laryngeal carcinoma have a high probability of cure after hyperfractionation
      radiotherapy. However, hyperfractionation radiotherapy induces a high degree of
      toxicity that reduces the laryngeal function preservation rate and may jeopardize
      overall survival.

PMID- 16955005
TI  - Repair of motor nerve gaps with sensory nerve inhibits regeneration in rats.
AB  - OBJECTIVE: Sensory nerve grafts are often used to reconstruct injured motor
      nerves, but the consequences of such motor/sensory mismatches are not well
      studied. Sensory nerves have more diverse fiber distributions than motor nerves
      and may possess phenotypically distinct Schwann cells. Putative differences in
      Schwann cell characteristics and pathway architecture may negatively affect the
      regeneration of motor neurons down sensory pathways. We hypothesized that sensory
      grafts impair motor target reinnervation, thereby contributing to suboptimal
      outcomes. This study investigated the effect of motor versus sensory grafts on
      nerve regeneration and functional recovery. STUDY DESIGN: The authors conducted a
      prospective, randomized, controlled animal study. METHODS: Fifty-six Lewis rats
      were randomized to seven groups of eight animals each. Five-millimeter tibial
      nerve defects were reconstructed with motor or sensory nerve grafts comprised of
      single, double, triple, or quadruple cables. Tibial nerve autografts served as
      positive controls. Three weeks after reconstruction, nerves were harvested for
      histologic examination and quantitative histomorphometric analysis. Wet muscle
      masses provided an index of functional recovery. RESULTS: Nerve regeneration was
      significantly greater across motor versus sensory nerve grafts independent of
      graft cross-sectional area or cable number. Motor grafts demonstrated increased
      nerve density, percent nerve, and total fiber number (P < .05). Normalized wet
      muscle masses trended toward improved recovery in motor versus sensory groups.
      CONCLUSIONS: Reconstruction of tibial nerve defects with nerve grafts of motor
      versus sensory origin enhanced nerve regeneration independent of cable number in
      a rodent model. Preferential nerve regeneration through motor nerve grafts may
      also promote functional recovery with potential implications for clinical nerve
      reconstruction.

PMID- 16955006
TI  - Postobstructive pulmonary edema after laryngospasm in the otolaryngology patient.
AB  - CONTEXT: Post-obstructive pulmonary edema (PPE) is an uncommon complication which
      develops immediately after the onset of acute airway obstruction such as
      laryngospasm or epiglottitis (type I) or after the relief of chronic upper airway
      obstruction such as adenotonsillar hypertrophy (type II). OBJECTIVE: To describe
      the development of type I PPE following laryngospasm in pediatric and adult
      patients undergoing otolaryngologic surgical procedures other than those for
      treatment of obstructive sleep apnea. DESIGN: Retrospective case series of 13
      otolaryngology patients from 1996 to 2003. SETTING: Tertiary care teaching
      hospital and its affiliates. PATIENTS: 13 patients (4 children, 9 adults, 5
      males, 8 females) ranging in age from 9 months to 48 years. RESULTS: Operative
      procedures included adenoidectomy, tonsillectomy, removal of an esophageal
      foreign body, microlaryngoscopy with papilloma excision, endoscopic sinus
      surgery, septorhinoplasty, and thyroidectomy. Six patients required reintubation.
      Treatment included positive pressure ventilation, oxygen therapy, and diuretics.
      Seven patients were discharged within 24 hours and the others were discharged
      between 2 and 8 days postoperatively. There were no mortalities. CONCLUSION:
      Laryngospasm resulting in PPE may occur in both children and adults after various
      otolaryngologic procedures. Among the subgroup of children, our study is the
      first to report its occurrence in healthy children without sleep apnea undergoing
      elective surgery.

PMID- 16955007
TI  - Retropharyngeal pseudomeningocele presenting as dysphagia after atlantooccipital
      dislocation.
AB  - EDUCATIONAL OBJECTIVE: At the conclusion of this paper, the readers should be
      able to recognize a retropharyngeal pseudomeningocele as a potential complication
      of atlanto occipital dislocation. OBJECTIVES: To demonstrate how a
      retropharyngeal pseudomeningocele may present as dysphagia in a patient who is
      recovering from atlanto occipital dislocation as well as to discuss the treatment
      options in this situation. STUDY DESIGN: Case report and literature review.
      METHODS: Analysis of a case through medical record and literature review.
      RESULTS: A retropharyngeal pseudomeningocele is a very rare complication of
      atlanto occipital dislocation. It may develop weeks after the initial injury and
      can present with respiratory or swallowing difficulties. Decompression via a
      ventriculoperitoneal or lumboperitoneal shunt facilitates resolution of the
      cerebral spinal fluid collection. CONCLUSIONS: A retropharyngeal
      pseudomeningocele should be considered in all patients status post-atlanto
      occipital dislocation who are experiencing respiratory distress or dysphagia.

PMID- 16955008
TI  - Auditory brainstem implant in a child with severely ossified cochlea.
AB  - OBJECTIVE: The hearing outcome after implanting a severely ossified cochlea has
      always been less satisfactory than implanting a patent one. The aim of our study
      is to present a case where brainstem implantation was successfully performed as
      an alternative to cochlear implantation in a child with bilateral severe
      ossification of the cochlea. STUDY DESIGN: Case presentation. This study was
      conducted at Gruppo Otologico, Rome, Italy, a private referral center for
      neurotology and skull base surgery. METHODS: The subject of our study was a 12
      year-old female child with postmeningitic deafness and bilaterally ossified
      cochleae. This case is the first brainstem implantation performed at our center
      with the indication of severe ossification of the cochlea. RESULTS: Successful
      brainstem implantation of a device was carried out, and the hearing of the
      patient was restored to the degree that she can freely use the telephone after 8
      months of implantation. CONCLUSION: Although more cases are needed before
      establishing the exact outcome of brainstem implantation in cases of deafness in
      the presence of severe bilateral cochlear ossification, preliminary results show
      the superiority of brainstem implants to conventional or even customized cochlear
      implants.

PMID- 16955009
TI  - Late-onset medullary carcinoma of the thyroid: need for genetic testing and
      prophylactic thyroidectomy in adult family members.
AB  - OBJECTIVE: Sporadic late-onset medullary carcinoma of the thyroid is quite rare.
      Usually, the patient presents with a thyroid mass or neck node metastasis along
      with high levels of calcitonin and preoperative fine needle aspiration biopsy
      suggestive of medullary carcinoma of the thyroid. The role of genetic testing in
      such individuals, along with testing of other family members, remains somewhat
      unclear at this stage, especially in patients presenting with familial medullary
      thyroid carcinoma. Genetic testing with RET proto-oncogene mutational studies is
      very popular in familial medullary thyroid carcinoma, especially in children,
      with routine prophylactic thyroidectomy. However, its indications in adults
      remain unclear at this time. CASE STUDY: Recently, a 69-year-old woman presented
      with a thyroid mass and underwent total thyroidectomy and central compartment
      dissection. She was found to have medullary carcinoma of the thyroid. The patient
      had four children, three of whom were found to have a RET mutation similar to
      their mother's, V804M. In view of the RET mutation, the three children were
      offered prophylactic thyroidectomy at ages 42, 45, and 47. The patient's son was
      noted to have extensive C-cell hyperplasia in both lobes of the thyroid. The
      other two individuals had benign pathology with no evidence of C-cell
      hyperplasia. CONCLUSIONS: There is no definite consensus of opinion about the
      need for prophylactic total thyroidectomy in adults with RET mutation. The rarely
      reported 804 mutation is, however, a predictor of medullary carcinoma of the
      thyroid. One individual in this group had extensive C-cell hyperplasia,
      suggesting that he would have developed medullary carcinoma of the thyroid in the
      future. Prophylactic thyroidectomy should be recommended in patients with RET
      mutation and a family history of medullary carcinoma of the thyroid; however, its
      role in adult family members needs to be evaluated with larger registry of
      prophylactic thyroidectomy. Whether these adults with rare 804-mutation could be
      observed and followed with serial calcitonin, ultrasound, or calcitonin
      stimulation tests remains to be studied.

PMID- 16955010
TI  - Benefits of fibrin sealants in parotidectomy: is underflap suction drainage
      necessary?

PMID- 16955011
TI  - The Agger Nasi Punch-Out Procedure (POP): maximizing exposure of the frontal
      recess.

PMID- 16955012
TI  - Preservation of the marginal mandibular branch of the facial nerve using a plexus
      block nerve stimulator.
AB  - Preserving the marginal mandibular branch of the facial nerve is essential in
      submandibular neck dissection to avert disfiguring complications. Despite the
      high incidence of postoperative palsy, old-fashioned techniques of nerve
      identification remain widespread. The use of disposable plexus block nerve
      stimulators as a safe and accurate method to localize the nerve intraoperatively
      is suggested herein. Such devices are significantly more affordable and user
      friendly than larger facial nerve monitoring devices, which are rather favored
      for those procedures more extensively jeopardizing the branches of the facial
      nerve. In this report, disposable stimulators led to successful identification of
      the nerve in 100% of 25 patients between 2003 and 2005, with no postoperative
      paralysis. In addition, stimulation devices are constantly gaining in reliability
      and safety, and the number of surgical fields supporting their use is expanding.
      Therefore, their routine use for surgery on the submandibular area is recommended
      by the authors.

PMID- 16955013
TI  - Treatment of chronic posterior laryngitis with esomeprazole.

PMID- 16955016
TI  - Minimally invasive thyroidectomy using the Sofferman technique.

PMID- 16955017
TI  - RE: Alexander TH, Davidson TM. Intranasal zinc and anosmia: the zinc-induced
      anosmia syndrome. Laryngoscope 2006;116:217-220.

PMID- 16955018
TI  - Re: Alexander TH, Davidson TM. Intranasal zinc and anosmia: the zinc-induced
      anosmia syndrome. Laryngoscope 2006;116:217-220.

PMID- 16955020
TI  - Vocal fold medialization by autologous fascia transplantation.

PMID- 16955024
TI  - Posttraumatic peripherally-induced dystonia and multifocal deep brain
      stimulation: case report.
AB  - OBJECTIVE: We report on the effect of multifocal deep brain stimulation for the
      treatment of posttraumatic peripherally-induced dystonia. CLINICAL PRESENTATION:
      A 34-year-old woman presented with an 8-year history of painful tonic dystonia
      starting in her left leg after injury of the third metatarsal bone. She did not
      benefit from right-sided pallidal stimulation by an electrode misplaced in the
      globus pallidus externus in another hospital. INTERVENTION: Quadripolar deep
      brain stimulation electrodes were placed in the globus pallidus internus and the
      ventrolateral thalamus by computed tomographic-guided stereotactic surgery and
      microelectrode recording contralateral to the side of dystonia. The Burke-Fahn
      Marsden motor score of 34 did not improve with chronic pallidal or thalamic
      stimulation. CONCLUSION: Although deep brain stimulation is received with great
      enthusiasm, it is important to identify its limitations in certain subtypes of
      dystonia.

PMID- 16955025
TI  - Follicular lymphoma of the dura: case report.
AB  - OBJECTIVE: We present an unusual dural-based follicular lymphoma with
      radiological and macroscopic features similar to a meningioma. The unusual
      location of this tumor and its distinction from meningioma, mucosa-associated
      lymphoid tissue-type marginal zone B-cell lymphoma of the dura, and
      intraparenchymal central nervous system lymphoma, dramatically alters the
      patient's postoperative treatment. The case illustrates the clinical,
      radiological, and histological relevance of this rare entity. CLINICAL
      PRESENTATION: A 41-year-old Caucasian man with chronic bifrontal headaches and a
      raised area over his left frontal cranium that persisted for 1 year presented to
      the emergency room with nausea and vomiting. His family reported that the patient
      demonstrated increased irritability and aggressive behavior. A computed
      tomographic scan revealed a large mass of the left frontal convexity with edema
      and mass effect. Magnetic resonance imaging scans showed a 5-cm homogeneously
      enhancing mass in the left posterior frontal lobe. INTERVENTION: Preoperatively,
      the patient underwent angiography and embolization of the tumor. The patient
      underwent gross total resection of tumor. The dural-based tumor invaded the
      cranium and scalp. Neuropathological findings were consistent with low-grade
      follicular lymphoma. The patient is currently undergoing radiation and
      chemotherapy. CONCLUSION: The current case represents the first report of
      extensive intracranial dural involvement by a follicular lymphoma that shows a
      classic immunophenotype by immunohistochemistry and flow cytometry. The case
      illustrates the clinical and radiographic similarities between dural-based
      lymphoma and meningioma. Distinguishing dural-based follicular lymphoma from
      mucosa-associated lymphoid tissue-type lymphoma and from intraparenchymal primary
      central nervous system lymphomas, which are more often large cell lymphomas with
      more aggressive biological behavior, is essential for proper clinical management.

PMID- 16955026
TI  - Internal jugular venous thrombosis as a complication after an elective anterior
      cervical discectomy: case report.
AB  - OBJECTIVE: Anterior cervical discectomy is one of the most common spine
      procedures in neurosurgery. Various complications, including hoarseness,
      hematoma, and dysphagia, have been reported in the literature. We report the
      first case of internal jugular venous thrombosis after an elective anterior
      cervical discectomy. CLINICAL PRESENTATION: A 35-year-old woman with past medical
      history significant only for hypercholesterolemia and cholecystectomy underwent
      an anterior cervical discectomy with fusion for a symptomatic cervical disc at
      the C5-C6 level. Intraoperatively, the patient had venous bleeding, which was
      adequately controlled. The procedure was completed with good hemostasis before
      closure. The patient was discharged home 1 day after the surgery. She was
      readmitted 5 days later with a 2-day history of a swollen right neck. The patient
      had no respiratory symptoms, but did report mild dysphagia. A hematoma was
      suspected. INTERVENTION: A computed tomographic scan of the neck was performed
      when the patient presented with cervical swelling. This was suggestive of a right
      internal jugular venous thrombosis. This diagnosis was confirmed with cervical
      ultrasound. The patient was seen by the vascular surgery department. The hospital
      course was otherwise uneventful and the patient was discharged 3 days later on
      oral anticoagulation with warfarin. CONCLUSION: This is the first report of
      internal jugular venous thrombosis after an elective anterior cervical
      discectomy. Internal jugular venous thrombosis should be considered in the
      differential diagnosis of a patient presenting with cervical swelling after an
      anterior cervical discectomy.

PMID- 16955027
TI  - Ectopic fascioliasis in the dorsal spine: case report.
AB  - OBJECTIVE: Parasitic myelopathy is rare. We report ectopic infestation of the
      spine by Fasciola hepatica. CLINICAL PRESENTATION: A young woman presented with
      gradual onset paraplegia with bladder and bowel involvement. A magnetic resonance
      imaging scan showed an epidural mass lesion that was isotense on T1-weighted
      images and hyperintense on T2-weighted images, extending from T4-T7 vertebra with
      extradural cord compression. She was diagnosed with cord compression, possibly
      owing to tubercular epidural granulation tissue. INTERVENTION: During surgery, a
      mobile, flat, leaf-like, pink parasite was found in the epidural space.
      Morphological and histological indices confirmed the parasite as Fasciola
      hepatica. CONCLUSION: Ectopic spinal localization of Fasciola may occur during
      the transmigration path of the parasite through peritoneum or from the liver
      through portal venous system.

PMID- 16955031
TI  - Magnetoencephalography in neurosurgery.
AB  - OBJECTIVE: To present applications of magnetoencephalography (MEG) in studies of
      neurosurgical patients. METHODS: MEG maps magnetic fields generated by electric
      currents in the brain, and allows the localization of brain areas producing
      evoked sensory responses and spontaneous electromagnetic activity. The identified
      sources can be integrated with other imaging modalities, e.g., with magnetic
      resonance imaging scans of individual patients with brain tumors or intractable
      epilepsy, or with other types of brain imaging data. RESULTS: MEG measurements
      using modern whole-scalp instruments assist in tailoring individual therapies for
      neurosurgical patients by producing maps of functionally irretrievable cortical
      areas and by identifying cortical sources of interictal and ictal epileptiform
      activity. The excellent time resolution of MEG enables tracking of complex
      spaciotemporal source patterns, helping, for example, with the separation of the
      epileptic pacemaker from propagated activity. The combination of noninvasive
      mapping of subcortical pathways by magnetic resonance imaging diffusion tensor
      imaging with MEG source localization will, in the near future, provide even more
      accurate navigational tools for preoperative planning. Other possible future
      applications of MEG include the noninvasive estimation of language lateralization
      and the follow-up of brain plasticity elicited by central or peripheral neural
      lesions or during the treatment of chronic pain. CONCLUSION: MEG is a mature
      technique suitable for producing preoperative "road maps" of eloquent cortical
      areas and for localizing epileptiform activity.

PMID- 16955032
TI  - Endoscopic transsphenoidal surgery: stone-in-the-pond effect.
AB  - THE TRANSSPHENOIDAL MIDLINE route represents the standard approach to the
      pituitary and sellar area and is used for more than 95% of surgical indications
      in this region. It is the least traumatic route to the sella turcica, it avoids
      brain retraction, and it provides excellent visualization of the pituitary gland
      and lesions related to that structure. The technique has essentially replaced
      craniotomy and has been used by every pituitary neurosurgeon, representing the
      "gold standard" of the transsphenoidal approach to the sellar region for more
      than 30 years. The introduction of endoscopic techniques has produced a "stone-in
      the-pond" effect, influencing the relatively peaceful neurosurgical environment.
      The brilliant increased vision of the surgical target offered by the endoscope
      can allow more effective removal of the lesion, followed by superior clinical
      results and a reduction in the incidence of complications. Endoscopy contributes
      to better and more contemporary knowledge of the possibilities of the
      transsphenoidal approach, thus increasing the extended approaches, not only for
      the pituitary area. Whether or not the transsphenoidal approach should be
      performed with the use of the microscope or the endoscope is finally discussed.

PMID- 16955033
TI  - Are primary supratentorial intracerebral hemorrhages surrounded by a biochemical
      penumbra? A microdialysis study.
AB  - OBJECTIVE: Opinions vary regarding the indications for surgical evacuation of
      spontaneous intracerebral hemorrhages (ICH) and whether or not penumbra zones
      surround them. METHODS: We performed intracerebral microdialysis (mean duration,
      3.5 d) after surgical evacuation of ICH in 22 patients. Probes were placed in the
      parenchyma within 1 to 2 cm of the evacuated hematoma; a postoperative computed
      tomographic scanning verified their positions. The catheters were perfused with
      an artificial cerebrospinal fluid solution at 0.3 microl/min. Biochemical
      variables (glucose, pyruvate, lactate, glutamate, and glycerol) were analyzed and
      displayed at the bedside. The levels obtained were compared with previous data
      from normal human brains and the pericontusional penumbra zones of patients with
      severe traumatic brain lesions. RESULTS: During 1 to 12 hours after surgery,
      interstitial levels of glucose (median level, 1.3 mmol/L; interquartile range,
      0.6-2.2 mmol/L) were within normal variations, whereas the levels of lactate
      (median level, 6.4 mmol/L; interquartile range, 3.9-9.0 mmol/L), glutamate
      (median level, 14 micromol/L; interquartile range, 5-370 micromol/L), and
      glycerol (median level, 190 micromol/L; interquartile range, 74-380 micromol/L),
      as well as the lactate/pyruvate ratio (median ratio, 35; interquartile range, 23
      50) were increased. A gradual normalization of the lactate/pyruvate ratio and
      glycerol level was observed within 48 hours. CONCLUSION: The area close to an
      evacuated ICH exhibits a biochemical pattern similar to that of the biochemical
      penumbra zone surrounding focal traumatic brain contusions. The presence of a
      penumbra zone around large ICH may be of importance for making surgical
      decisions.

PMID- 16955034
TI  - Preoperative prediction of long-term outcome in poor-grade aneurysmal
      subarachnoid hemorrhage.
AB  - OBJECTIVE: To evaluate which presentation indices, demographics, and clinical
      information predict 12-month outcome in poor-grade aneurysmal subarachnoid
      hemorrhage (SAH), and to provide a preoperative index of prognosis. METHODS: Data
      were obtained on all patients with poor-grade (Hunt and Hess Grades IV and V)
      aneurysmal SAH from a prospectively maintained SAH database and health outcomes
      project. Demographics, medical history, presenting clinical condition, and health
      outcomes were analyzed. Survival analysis was performed and Kaplan-Meier curves
      were generated. Multivariable logistic regression analysis was used to identify
      significant predictors of poor outcome at 12 months after hemorrhage, as measured
      by the modified Rankin disability scale. RESULTS: Survival curves for open
      surgery and endovascular treatment did not differ significantly. Overall, 40% of
      the 98 definitively treated patients had a favorable outcome at 12 months.
      Multivariable analysis identified patient age older than 65 years (P < 0.001),
      hyperglycemia (P < 0.03), worst preoperative Hunt and Hess Grade V (P < 0.0001),
      and aneurysm size of at least 13 mm (P < 0.002) as significant predictors of poor
      outcome. These variables were weighted and used to compute a poor-grade
      aneurysmal SAH Prognosis Score (hereafter, Prognosis Score) for each patient. A
      Prognosis Score of 0 was associated with a 90% favorable outcome; Prognosis Score
      of 1 with 83%; Prognosis Score of 2 with 43%; Prognosis Score of 3 with 8%;
      Prognosis Score of 4 with 7%; and a Prognosis Score of 5 with 0%. CONCLUSION:
      Outcome in poor-grade aneurysmal SAH is strongly predicted by patient age, worst
      preoperative Hunt and Hess clinical grade, and aneurysm size. Hyperglycemia on
      admission after poor-grade aneurysmal SAH increases the likelihood of poor
      outcome, and is a potentially modifiable risk factor. The Prognosis Score is a
      useful tool for preoperatively assessing the likelihood of a favorable outcome
      for poor-grade aneurysmal SAH patients.

PMID- 16955035
TI  - Endoscopic third ventriculostomy for occlusive hydrocephalus caused by cerebellar
      infarction.
AB  - OBJECTIVE: The surgical management of occlusive hydrocephalus caused by massive
      cerebellar infarction remains controversial. The procedures that are more
      commonly used to avoid progressive neurological deterioration are based on
      transient external ventricular drainage or the placement of permanent shunt
      systems. To our knowledge, this is the first report regarding using endoscopic
      third ventriculostomy (ETV) in patients with an occlusive hydrocephalus caused by
      cerebellar ischemic stroke. We report our experience of 10 reviewed cases.
      METHODS: Between 1997 and 2004, 10 patients with a resulting hydrocephalus caused
      by a space-occupying cerebellar infarction were managed with ETV. Glasgow Coma
      Scale score on admission, cause of stroke, and computed tomographic signs,
      including the ischemic vascular territory involved and brain edema, were noted.
      Clinical outcome was evaluated using the Glasgow Outcome Scale. RESULTS: In all
      patients, there was a mean interval of 4 days from the onset of deterioration of
      consciousness to operation. Mean Glasgow Coma Scale score on admission was 11.2.
      In nine patients, ETV was the initial procedure of ventricular drainage. One
      patient was primarily treated with an external ventricular drainage, but the
      device dislocated and ETV was performed. In one patient, an external ventricular
      drainage became necessary 7 days after the initial ETV because of a malfunction
      of the stoma. One patient showed a progressive brain edema 2 days after ETV, and
      suboccipital decompression was performed. Eight successfully treated patients
      demonstrated an improvement in the level of consciousness after ETV. Mean Glasgow
      Outcome Scale score on discharge of all patients was 3.4. CONCLUSION: Occlusive
      hydrocephalus caused by cerebellar infarction is infrequent. When occlusive
      hydrocephalus is observed, ETV can be used successfully with minimal risks,
      especially with avoidance of a higher rate of infectious complications caused by
      external drainage systems.

PMID- 16955036
TI  - Impact of cerebrovascular disease on the surgical treatment of idiopathic normal
      pressure hydrocephalus.
AB  - OBJECTIVE: The influence of cerebrovascular disease (CVD) on the short- and long
      term results of surgery was evaluated in a series of consecutive patients with
      idiopathic normal-pressure hydrocephalus (iNPH). METHODS: Patients with suspected
      iNPH admitted to our department between June 1996 and June 2003 were evaluated
      with four clinical and handicap scales. CVD and risk factors for vascular disease
      were rated. All patients underwent intracranial pressure monitoring via a spinal
      catheter. Sixty-six patients received a ventriculoperitoneal shunt with a
      programmable valve. Prospective assessments were programmed at 2 weeks and 3
      months after surgery (short-term follow-up). Long-term follow-up evaluations were
      arranged in June 2004 with patients and/or relatives and health/home care
      assistants. RESULTS: At the short-term follow-up examination, a significant
      clinical improvement was globally present in 89% of the patients (P < 0.05). CVD,
      such as leucoaraiosis or previous strokes, were present in 71% of the patients.
      Patients both with and without CVD and/or risk factors for vascular disease
      presented a significant improvement (P < 0.05) after shunting; 85 and 100% of the
      patients with and without CVD, respectively. At the long-term follow-up
      examination (mean, 52 +/- 24.8 mo), 24% of the patients were dead and 8% had
      experienced stroke. Globally, 60% of the patients were still improved (P < 0.05);
      52 and 79% of the patients with and without CVD, respectively. CONCLUSION: A high
      success rate in treatment of iNPH is possible in patients with and without CVD.
      Despite poorer short- and long-term treatment outcome of iNPH patients with CVD,
      a long-lasting improvement in their quality of life favors surgery.

PMID- 16955037
TI  - Outcomes of surgery for resection of regions of symptomatic radiation injury
      after stereotactic radiosurgery for arteriovenous malformations.
AB  - OBJECTIVE: Although radiation injury after stereotactic radiosurgery (SRS),
      including radiation necrosis (RN), is often treated with surgical resection,
      detailed outcome data are lacking after resection of symptomatic radiation
      injured regions with imaging characteristics suspicious for RN after SRS for
      arteriovenous malformations (AVM). We present outcomes in seven such patients.
      METHODS: We conducted a retrospective chart review of seven patients with AVMs of
      Spetzler-Martin Grades II (n = 1), III (n = 2), and IV (n = 4) who underwent
      helium ion, proton beam, or gamma knife SRS and required resection of RN
      suspicious tissue 1 to 24 months after post-SRS symptom onset. Postoperative
      outcomes included Karnofsky Performance Scale (KPS) score and time to symptomatic
      improvement. RESULTS: Symptomatic improvement required at least 9 months in the
      three patients with large regions suspicious for RN (>or=4 cm), whereas of four
      patients with smaller regions (<4 cm), three showed improvement within 2 months
      (P < 0.05). The remaining patient, who showed no benefit, underwent resection 2
      years after the onset of RN symptoms (compared with <or= 8 mo for the other six
      patients). Surgery improved KPS scores in four patients with a preoperative KPS
      score of 50 or lower, but not in three patients with preoperative KPS scores
      greater than 70 (P < 0.05). Outcomes were not consistently associated with AVM
      size or location, SRS treatment volume or dose, associated aneurysm, or residual
      AVM. CONCLUSION: After SRS for AVMs, resection of symptomatic RN-suspicious
      tissue areas is beneficial in reversing neurological deficits and improving KPS
      scores in selected patients. Times to improvement were longer when larger areas
      were resected. Delaying such surgery after symptom onset may negatively affect
      improvement.

PMID- 16955038
TI  - Glomus jugulare tumors: the option of gamma knife radiosurgery.
AB  - OBJECTIVE: Glomus jugulare tumors are generally considered slow-growing, benign
      lesions. However, their pronounced local aggressiveness frequently results in
      severe neurological deficits. Surgical removal is rarely radical and is usually
      associated with morbidity. There is increasing evidence that stereotactic
      radiosurgery, particularly gamma knife radiosurgery (GKR), may play a relevant
      role as a therapeutic option in these tumors. METHODS: Between 1996 and 2005, we
      used GKR to treat 20 patients bearing growing glomus jugulare tumors, mostly
      classified as Glasscock-Jackson Grade IV or Fisch Stage D1. Follow-up (mean,
      50.85 mo) data was available for 20 patients (four men, 16 women; mean age, 56
      yr): eight out of 20 tumors were surgical recurrences, three out of 20 patients
      had GKR as the primary treatment, and 11 out of 20 patients previously underwent
      endovascular embolization. Regarding the radiosurgical dose planning, the average
      tumor volume was 7.03 cm (range, 1.5-13.4 cm) and the mean marginal dose was 17.3
      Gy (range, 13-24 Gy). RESULTS: Neurological signs and symptoms were unchanged in
      13 out of 20 patients. An improvement of cranial nerve function was observed in
      five patients and hearing deterioration was observed in two patients. Tumor
      volume was unchanged in 11 out of 20 patients and was slightly (<or= 20%)
      decreased in eight out of 20 patients. In one unusual case of a bulky cavernous
      sinus recurrence, neoplastic regression was particularly pronounced. CONCLUSION:
      Despite the constraints of the limited case material, considering the estimated
      doubling time of these rare tumors (4.2 yr), our preliminary results with GKR at
      a mid-term follow-up examination suggest an effective tumor growth control with
      negligible incidence of untoward sequelae.

PMID- 16955039
TI  - Visual outcome of tuberculum sellae meningiomas after extradural optic nerve
      decompression.
AB  - OBJECTIVE: Meningiomas of the tuberculum sellae have a close relationship with
      the optic apparatus. Even modern series show a 10 to 20% risk of visual
      deterioration after surgery. We have attempted to improve visual outcome by
      extradural decompression of the optic canal and anterior clinoid process,
      followed by intradural release of the optic nerve; this study provides an
      analysis of visual outcomes with this approach. METHODS: Treatment,
      histopathology, and follow-up data of 29 consecutive patients undergoing surgery
      for tuberculum sellae meningiomas with initial release of the optic nerve were
      prospectively collected. RESULTS: Radical tumor removal was possible in all 23
      patients with primary tumors and in three out of six patients with recurrent
      tumors. All patients but two of the worst affected with preoperative visual
      compromise improved from surgery; there were no instances of visual
      deterioration. Five patients with normal preoperative vision remained intact and
      visual improvement was 22 (91%) out of 24 patients in the remaining patients. In
      total, 13 patients (42%) had completely normal vision at follow-up. Mainly
      patients younger than 60 years experienced complete normalization after surgery.
      Two patients underwent transsphenoidal surgery for cerebrospinal fluid leaks.
      Postoperative endocrinological symptoms were temporary diabetes insipidus in one
      patient and permanent diabetes insipidus in another patient undergoing elective
      sectioning of the pituitary stalk because of a recurrent tumor with invasive
      growth into the stalk. CONCLUSION: Adding early optic nerve decompression by
      extradural clinoidectomy and optic canal unroofing to a frontopterional approach
      seemed to improve visual outcomes because there were no instances of visual
      deterioration. Simpson Grade 1 to 2 removal was possible in all patients with
      primary surgery, whereas recurrent cases could only be treated with lower grades
      of radicality. Radical removal, however, required readiness to reoperate for
      cerebrospinal fluid leakage at the site of the drilled tumor origin in bone.

PMID- 16955040
TI  - Preservation of facial nerve function after postoperative vasoactive treatment in
      vestibular schwannoma surgery.
AB  - OBJECTIVE: Facial nerve paresis and hearing loss are common complications after
      vestibular schwannoma surgery. Experimental and clinical studies point to a
      beneficial effect of nimodipine and hydroxyethyl starch for preservation of
      cochlear nerve function. A retrospective analysis was undertaken to evaluate the
      effect of vasoactive treatment on facial nerve outcome. PATIENTS AND METHODS:
      Forty-five patients with vestibular schwannoma removal, intraoperative
      electromyographic monitoring, and postoperative deterioration of facial nerve
      function were evaluated. Twenty-five patients underwent vasoactive treatment
      consisting of nimodipine and hydroxyethyl starch for improvement of hearing
      outcome. Twenty patients did not receive such treatment. Facial nerve function
      was evaluated before and after surgery, as well as 1 year after the surgical
      procedure. Patients were comparable regarding age, tumor size, and preoperative
      facial nerve function. RESULTS: Long-term results of facial nerve function were
      significantly improved in those patients who experienced severe postoperative
      deterioration of facial nerve function and received vasoactive treatment as
      compared with patients who did not receive nimodipine and hydroxyethyl starch
      after surgery. Treated patients showed a significantly higher rate of complete
      recovery compared with patients without treatment. CONCLUSION: The study points
      to a potential effect of vasoactive treatment for facial nerve function after
      vestibular schwannoma surgery. In particular, patients with postoperative
      disfiguring facial nerve palsy clearly benefit from intravenous hydroxyethyl
      starch and nimodipine with respect to a long-term socially acceptable facial
      nerve function.

PMID- 16955041
TI  - When the bone flap hits the floor.
AB  - OBJECTIVE: There is no published data in the neurosurgical literature describing
      the incidence, treatment, or outcome of contaminating a bone flap. We reviewed
      our departmental experience to determine methods of prevention and assess our
      treatment strategies. METHODS: We retrospectively reviewed all incidents of
      dropped bone flaps during a craniotomy at a single medical center during a 16
      year period. In addition, a questionnaire was mailed to neurosurgeons in the
      United States and abroad asking their own experience and method of management.
      RESULTS: Fourteen incidents of dropped bone flaps occurred during a 16-year
      period. Follow-up varied from 2 to 176 months. The bone flap was dropped while
      elevating the bone (n = 4), when handing the bone off the field (n = 4), and
      during plating (n = 4). The context was unknown in two cases. Management included
      soaking the flap in betadine and/or antibiotic solution (n = 8), autoclaving (n =
      2), or discarding the bone flap and replacing with a mesh cranioplasty (n = 3).
      The treatment remains unknown in one case. No instances of infection were noted
      in follow-up. In response to the survey, 66% (33 out of 50) of the polled
      neurosurgeons had experienced this complication during their practice, and 83%
      would replace the bone flap after disinfection. CONCLUSION: Dropping a bone flap
      during neurosurgery remains an uncommon but preventable complication. Treatment
      options include discarding the bone followed by cranioplasty versus replacing the
      bone after treatment with antibiotic irrigation, betadine, and/or autoclaving.
      Replacement after disinfection is an appropriate option for contaminated bone
      flaps that avoids the expense and time of cranioplasty.

PMID- 16955042
TI  - The comparative impact of video consultation on emergency neurosurgical
      referrals.
AB  - OBJECTIVE: Neurosurgical resources are concentrated in tertiary referral centers,
      whereas emergencies identified from district general hospitals are traditionally
      referred by telephone consultation (TC). Recent advances in communication
      technology offer the alternative options of teleradiology (TR) and video
      consultation (VC). This study aimed to determine the differences among these
      three consultation methods on the basis of their process-of-care indicators,
      clinical outcomes, and cost-effectiveness. METHODS: Patients with emergency
      neurosurgical conditions (head injury, stroke, and miscellaneous) from a district
      general hospital were randomized to three different modes of consultation: TC,
      TR, or VC. Process-of-care indicators (postresuscitation Glasgow Coma Scale
      score, consultation time required, diagnostic accuracy, and transfer decision and
      safety), 6-month clinical outcome, and cost-effectiveness of the three
      consultation modes were correlated. RESULTS: In a 3-year period, 710 patients
      were recruited and randomized to the three consultation modes (n = 235, 239, and
      236, respectively). Demographic and clinical data were comparable. TR and VC
      showed a definite advantage in diagnostic accuracy over TC (89.1 and 87.7% versus
      63.8%; P < 0.001). However, duration of the corresponding consultation process
      was longer for TR and VC than TC (1.01 and 1.3 h versus 0.70 h). A high failure
      rate (30%) was noted in VC. Thirty-three percent of patients were transferred to
      the neurosurgical center after consultation. The difference in consultation modes
      did not have an impact on transfer rate and safety. There was a trend toward more
      favorable outcome (61%; P = 0.12) and a reduced mortality (25%; P = 0.025) in TR
      compared with TC (54 and 34%, respectively) and VC (54 and 33%, respectively).
      The mean cost per patient in the VC group was slightly higher than the other two
      groups (TC versus TR versus VC = 14,000 US dollars versus 14,400 US dollars
      versus 16,300 US dollars, respectively), but the differences were not
      statistically significant. CONCLUSION: Emergency neurosurgical consultation
      assisted by TR and VC achieved a higher diagnostic accuracy in comparison with
      conventional TC. Although VC did not show an advantage over TR in process-of-care
      indicators, clinical outcome, and cost, it has been proven to be a safe mode of
      consultation in emergency neurosurgery.

PMID- 16955043
TI  - Volumetric measurement of the pontomesencephalic cistern in patients with
      trigeminal neuralgia and healthy controls.
AB  - OBJECTIVE: Most so-called idiopathic trigeminal neuralgias (TN) are caused by
      neurovascular compression. Does the size of the cerebellopontine cistern play a
      role in favoring a neurovascular conflict? The aim of this prospective study was
      to measure the volume of the parapontine cistern in patients with idiopathic TN
      and to perform a comparison with healthy controls. METHODS: In 25 patients with
      unilateral idiopathic TN and 17 healthy participants, high-resolution 1.5-T
      magnetic resonance imaging scans of the parapontine region and the trigeminal
      nerve were performed. A coronal T2-weighted, true fast imaging steady-state
      precession sequence with a slice thickness of 0.9 mm was used to define the
      surrounding cerebrospinal fluid space from the trigeminal root entry zone to
      Meckel's cave. The volume of the pontomesencephalic cistern was calculated using
      a standardized method. RESULTS: The mean difference of the volume of the affected
      and opposite side was 13% in patients with TN. In all patients, a significantly
      smaller volume of the cistern was found on the affected side (P < 0.01). Healthy
      controls showed a mean volumetric side difference of 9%, which was not
      significant (P > 0.05). CONCLUSION: High-resolution magnetic resonance imaging
      scans are able to demonstrate significant volumetric differences of the
      pontomesencephalic cistern in patients with unilateral TN. A smaller cistern may
      be correlated with the occurrence of a neurovascular compression, and these
      findings support the neurovascular compression theory in idiopathic TN.

PMID- 16955044
TI  - Difference in recovery potential of peripheral nerves after graft repairs.
AB  - OBJECTIVE: To our knowledge, few studies have been published regarding
      differences in nerve recovery potentials. In this study, sensory and motor
      recovery potentials were compared between different nerves. METHODS: A
      prospective study of a homogenous group of 393 graft repairs of the median,
      ulnar, radial, tibial, peroneal, femoral, and musculocutaneous nerves, with the
      scoring of motor and sensory recoveries. Sensory and motor recovery potentials,
      defined on the basis of average scores and rates of useful recovery, were
      compared between the different nerves, and separately for high-, intermediate-,
      and low-level repairs. RESULTS: Sensory recovery potential was similar for all
      nerves tested (P > 0.05), but motor recovery potential differed significantly.
      After high-level repairs, motor recovery potential was significantly better for
      the radial and tibial nerves (useful recovery in 66.7 and 54.5% of patients,
      respectively), than for the ulnar and peroneal nerves (useful recovery in 15.4
      and 13.8% of patients, respectively; P < 0.05). After intermediate-level repairs,
      motor recovery potential was better for the musculocutaneous, radial, and femoral
      nerves (useful recovery in 100, 98.3, and 87.5% of repairs, respectively), than
      for the tibial, median and ulnar nerves (useful recovery in 63.9, 52, and 43.6%
      of repairs, respectively; P < 0.05). In addition, motor recovery potential was
      significantly the worst with peroneal nerve repairs (useful recovery in 15.2% of
      patients; P < 0.05). After low-level repairs, motor recovery potential was
      similar for all nerves (useful recovery in the range of 88.9-100% of patients and
      in 56.3% of peroneal nerve repairs). CONCLUSION: Sensory recovery potential is
      similar for the median, ulnar, and tibial nerves. The expression of motor
      recovery potential depends on the repair level. With low- and high-level repairs,
      it does not stand out in an obvious way, but it is fully expressed with
      intermediate-level repairs, classifying nerves into three categories with
      excellent, moderate, and poor recovery potential.

PMID- 16955045
TI  - Cervical catheter tip placement for intrathecal baclofen administration.
AB  - OBJECTIVE: Intrathecal baclofen can reduce congenital and posttraumatic
      spasticity. Traditionally, the catheter tip for baclofen delivery is placed in a
      low thoracic position, which can result in a lumbar-to-cisternal cerebrospinal
      fluid baclofen concentration gradient. We investigated whether more rostral
      catheter placement was technically feasible, safe, and able to control upper
      extremity spasticity. METHODS: The records of 48 patients with a baclofen pump
      were reviewed retrospectively to evaluate the safety and efficacy of cervically
      placed intrathecal catheters for baclofen administration. Twenty-three patients
      had a catheter located in a cervical position and 25 had a catheter in a thoracic
      position (control group). Complications, including baclofen overdose, mechanical
      failures, and infections, were noted. Pre- and postoperative Ashworth scores were
      determined by a physical therapist using a standardized protocol. RESULTS: The
      mean duration of the follow-up period was 10 months. The groups were not
      significantly different in patient age, baclofen dose, or duration of follow-up,
      but differed somewhat in the causes of spasticity. For patients with a cervical
      catheter tip position, upper extremity Ashworth scores decreased significantly
      from 4.0 +/- 0.8 (standard deviation) preoperatively to 3.0 +/- 0.9
      postoperatively (P = 0.003). In both groups, lower extremity spasticity was
      significantly reduced. Postoperatively, one patient with a cervical catheter
      developed aspiration pneumonia, possibly because of sedation. Other complications
      included hardware infections, mechanical malfunctions, and pseudomeningoceles.
      CONCLUSION: In this series, placement of intrathecal baclofen catheters in the
      cervical region resulted in equal control of spasticity in the upper and lower
      extremities and did not increase complications related to the catheter position.

PMID- 16955046
TI  - Bone-mounted miniature robotic guidance for pedicle screw and translaminar facet
      screw placement: Part I--Technical development and a test case result.
AB  - OBJECTIVE: To introduce a new miniature robot (SpineAssist; MAZOR Surgical
      Technologies, Caesarea, Israel) that has been developed and tested as a surgical
      assistant for accurate percutaneous placement of pedicle screws and translaminar
      facet screws. METHODS: Virtual projections in three planes-axial, lateral, and
      anteroposterior-are reconstructed for each vertebra from a preoperative computed
      tomographic (CT) scan. On a specially designed graphic user interface with
      proprietary software, the surgeon plans the trajectory of the screws.
      Intraoperative fluoroscopic x-rays with targeting devices are then matched with
      the CT-based virtual images, as well as the surgeon's plan. A clamp is attached
      to the spinous process or a minimally invasive frame (Hover-T frame; MAZOR
      Surgical Technologies) is mounted to the iliac crest and one spinous process. The
      miniature robot is then attached to the clamp and/or frame. On the basis of
      combined CT scan and fluoroscopic data, the robot aligns itself to the desired
      entry point and trajectory, as dictated by the surgeon's preoperative plan.
      RESULTS: A test case in a cadaver lumbar spine was performed in which four screws
      and two rods were inserted, using a minimally invasive technique, combining the
      SpineAssist system and Hover-T frame in conjunction with the PathFinder system
      (Spinal Concept Inc., Austin, TX). The discrepancy between the planned and actual
      screw trajectories was measured by means of postprocedural CT scan. Overall, the
      four screws were implanted with an average deviation of 1.02 +/- 0.56 mm (range,
      0-1.5 mm) from the surgeon's plan. CONCLUSION: These preliminary results confirm
      the system's accuracy and support its use in minimally invasive spine surgery
      applications.

PMID- 16955047
TI  - Use of a volumetric target for image-guided surgery.
AB  - A VIRTUAL REALITY system has been devised to superimpose a computer-generated
      rendering of a volumetric target to be surgically approached or resected on a
      real-time video image of the surgical field. A stereotactic frame is used to
      register the image from the video camera with the image of the target volume for
      accurate localization. The volumetric target is obtained from preoperative
      imaging studies and can be modified to adjust the intended line of resection or
      to avoid eloquent vascular or neural tissue. The computer-generated image is
      updated throughout surgery to visualize only that part of the tumor under
      resection so the surgeon may guide the resection along the border of the mass or
      intended preplanned line of resection. To date, 74 intracranial tumor resections
      have been performed under video virtual reality guidance. Postoperative scanning
      corresponds in every case with preoperative planning. This system is also
      designed to be adapted to frameless guidance, which can be further enhanced by
      the incorporation of an audible tone to signal the relationship of the tip of the
      resection instrument to the line of resection.

PMID- 16955048
TI  - Absence of tight junctions between microvascular endothelial cells in human
      cerebellar hemangioblastomas.
AB  - OBJECTIVE: Endothelial tight junctions form the main barrier of the blood-brain
      barrier (BBB). In human hemangioblastomas, cyst formation is a common and
      important clinical manifestation. Although most researchers consider that the
      cyst formation in hemangioblastomas may be caused by the breakdown of the BBB,
      the underlying molecular mechanisms for cyst formation remain unknown. At
      present, there are few reports about the change of tight junctions in microvessel
      endothelium of human hemangioblastomas. The purpose of this research is to
      investigate the change of tight junction and its major molecular components in
      microvessel endothelium of human hemangioblastomas. METHODS: Twenty-four
      consecutive patients with cerebellar hemangioblastomas were studied. Tight
      junctions in the microvessels of hemangioblastomas and the control brain were
      examined by electron microscopy. Immunohistochemistry and double
      immunofluorescent microscopy were used to analyze the expression of CLN5 and its
      relationship with astrocytic endfeet in the control brain and hemangioblastomas.
      Quantitative real-time reverse-transcriptase polymerase chain reaction and
      Western blots were used to investigate the expression level of CLN5 in
      hemangioblastomas. Triple immunofluorescent microscopy was used to analyze the
      coexpression of vascular endothelial growth factor, vascular endothelial growth
      factor-R1, and placenta growth factor on microvessels of hemangioblastomas.
      Clinical and experimental data were correlated and analyzed by the one-way
      analysis of variance, Kruskal-Wallis test, and Spearman rank correlation test.
      RESULTS: In the control brain, the paracellular cleft between adjacent
      endothelial cells is sealed by continuous strands of tight junctions. In cystic
      hemangioblastomas, a significant paracellular cleft could be found between
      adjacent endothelial cells. Some endothelial cells were connected with adherens
      junction and no tight junction was found between them. Compared with the control
      brain, expression of CLN5 was decreased in cystic hemangioblastomas (P < 0.05).
      Phosphorylated CLN5 was detected in most hemangioblastomas, but not in the
      control brain. Microvessels in hemangioblastomas showed a significant absence of
      astrocytic endfeet. Coexpression of vascular endothelial growth factor, vascular
      endothelial growth factor-R1, and placenta growth factor was detected in the
      endothelial cells. The Spearman rank correlation test showed a significant
      correlation between a greater degree of CLN5 expression and less morphological
      cystic formation in these patients studied (correlation coefficient = -0.520; P =
      0.009). CONCLUSION: The continuity of tight junctions of the BBB is interrupted
      in human cerebellar hemangioblastomas. Significant absence of astrocytic endfeet
      and tight junctions can be found in microvessels of hemangioblastomas, which may
      lead to the breakdown of the BBB in these tumors. These findings suggest that the
      absence of tight junctions might play a role in cyst formation of
      hemangioblastomas.

PMID- 16955049
TI  - Correlation of postmortem 9.4 tesla magnetic resonance imaging and
      immunohistopathology of the human thoracic spinal cord 7 months after traumatic
      cervical spine injury.
AB  - OBJECTIVE: To correlate high-resolution magnetic resonance imaging (MRI) with
      immunohistopathology in the injured human spinal cord. METHODS: Postmortem MRI
      scans at a field strength of 9.4 T, as well as standard histology and
      immunohistochemistry, were performed on an excised specimen of human high
      thoracic spinal cord, obtained 7 months after the initial trauma, several
      segments below a severe spinal cord lesion (C5). RESULTS: A precise correlation
      is described between MRI and immunohistochemistry of the long white matter tracts
      undergoing Wallerian degeneration and of an extension of the cervical lesion into
      the high thoracic cord. CONCLUSION: MRI, the only imaging technique that
      currently provides useful information on the spinal cord parenchyma after trauma,
      is rapidly evolving. High-field scanners of up to 9.4 T are being clinically
      tested. The present postmortem investigation of an isolated spinal cord specimen
      demonstrates the precise correlation that can be achieved between imaging and
      pathology. In future investigations, this type of technique can lead to a more
      precise description of spinal cord injuries and their consequences in remote
      tissue. Translation into the clinical setting will improve diagnosis and follow
      up of spinal cord injured patients.

PMID- 16955050
TI  - Administration of ex vivo-expanded bone marrow-derived endothelial progenitor
      cells attenuates focal cerebral ischemia-reperfusion injury in rats.
AB  - OBJECTIVE: This study aimed to examine early effects of ex vivo-expanded bone
      marrow-derived endothelial progenitor cells (EPCs) on focal cerebral ischemia
      reperfusion injury. METHODS: EPCs were obtained from mononuclear cells of
      autologous bone marrow of a rat. After culture on fibronectin-coated dishes for
      10 to 14 days, 2.5 x 10 cells of EPCs were administered transarterially after 90
      minute occlusion of the middle cerebral artery. RESULTS: Administration of EPCs
      significantly reduced both the infarct volume and the scores of neurological
      deficits at 24 and 48 hours. EPCs administered 2 hours after insult did not
      reduce infarct volume, but attenuated neurological deficits at 24 hours.
      Administration of EPCs significantly reduced the number of myeloperoxidase
      immunoreactive cells in the ischemic lesion at 24 hours and increased regional
      cortical blood flow at 48 hours. EPCs were observed in the ischemic hemisphere
      and around the endothelial layer of the pial arteries. Most of them expressed
      endothelial nitric oxide synthase. CONCLUSION: Administration of ex vivo-expanded
      bone marrow-derived EPCs reduced infarct volume and neurological deficits in
      acute focal brain ischemia-reperfusion injury caused, at least in part, by
      attenuation of endothelial dysfunction.

PMID- 16955051
TI  - Expression of hypoxia-inducible factor-1 and vascular endothelial growth factor
      in response to venous hypertension.
AB  - OBJECTIVE: Experimentally, a fistula created surgically between the carotid
      artery and jugular vein, together with occlusion of venous sinuses, generate
      venous hypertension, which can induce dural arteriovenous fistula formation
      intracranially in rats. Our aim was to study the effect of nonischemic venous
      hypertension on the elaboration of the angiogenic signal, hypoxia-inducible
      factor-1 (HIF-1), and its downstream signal, vascular endothelial growth factor
      (VEGF). METHODS: Sixty rats were exposed to venous hypertension for periods
      ranging from 4 hours to 3 weeks. Western blot analysis, transbinding assays,
      enzyme-linked immunosorbent assays, and immunohistochemistry quantified HIF-1 and
      VEGF expression in brain. Forty-eight control rats underwent similar surgical
      procedures without creating venous hypertension. Cerebral blood flow was measured
      at baseline, after surgery, and before sacrifice. RESULTS: Venous hypertension
      did not impair cerebral blood flow. Relative to controls, HIF-1 expression
      increased fivefold in response to venous hypertension (P < 0.005), with peak
      expression 1 day later localized to endothelial cells in venules next to the
      sagittal sinus. VEGF expression also increased threefold in response to venous
      hypertension (P < 0.05), with peak expression 7 days later localized to
      parasagittal astrocytes. HIF-1 and VEGF were minimally expressed in rat normal
      venous pressures. CONCLUSION: In this model, venous hypertension stimulates
      angiogenesis by a mechanism other than ischemia. HIF-1 expression may result from
      dilation of parasagittal veins and endothelial deformation. HIF-1 and VEGF seem
      to be molecular agents that convert venous hypertension into intracellular
      signals and angiogenesis activity.

PMID- 16955052
TI  - Dr. Benno Schlesinger: neuroanatomist and neurosurgeon from Vienna, 1900-1983.
AB  - Benno Schlesinger (1900-1983) was a neurosurgeon, neuroanatomist, and neurologist
      from Vienna, Austria. He was a great person and a brilliant scientist.
      Schlesinger's life is a picture-book reflection of Europe's tragedy in the first
      half of the 20th century. Born an Austrian of Jewish descent, he left his home
      country and went to the United States where he spent the better part of his life
      engaging in painstaking research on a wide range of subjects, writing unique
      research papers on neuroanatomy, and working as a successful neurosurgeon. He
      made lasting contributions to our understanding of the surgical anatomy of the
      venous system of the brain and the effects of brain lesions on higher cortical
      functions. His intimate personal friendship with Harvey Cushing went far beyond
      their shared enthusiasm for neurosurgery.

PMID- 16955054
TI  - Proactive monitoring and management of the chronic heart failure patient.
      Introduction.

PMID- 16955055
TI  - How well are chronic heart failure patients being managed?
AB  - Heart failure (HF) remains a major public health problem, affecting 5 million
      patients in the United States. The personal burden of HF includes debilitating
      symptoms, activity limitations, frequent hospitalizations, arrhythmias, and
      increased mortality. Despite the compelling scientific evidence that angiotensin
      converting enzyme inhibitors, beta-blockers, and aldosterone antagonists reduce
      hospitalizations and mortality in patients with HF, these life-prolonging
      therapies continue to be underutilized. Device therapy for HF, including
      implantable cardioverter defibrillators and cardiac resynchronization therapy,
      has recently been demonstrated to also result in substantial mortality reduction.
      Accurate evaluation of patients with HF is critical for the appropriate selection
      and monitoring of therapy to reduce symptoms as well as for the prevention of
      recurrent hospitalizations. A number of studies in a variety of clinical settings
      have documented that a significant proportion of patients with HF are not
      receiving treatment with guideline-recommended, evidence-based therapies.
      Treatment gaps have also been documented in providing other components of care
      for patients with HF, including assessment for congestion and patient education.
      Recent studies demonstrate that hospital-based systems can improve medical care
      and education of hospitalized HF patients and accelerate use of evidence-based,
      guideline-recommended therapies by administering them before hospital discharge.
      HF disease management programs have also been shown to improve HF treatment,
      resulting in substantial reduction in hospitalizations and mortality. Application
      of validated and reproducible noninvasive techniques to monitor patients with
      chronic HF is an important step in maximizing interventions to improve outcomes
      in this patient population. Further efforts are clearly needed to improve the
      monitoring of HF patients in the hospital and outpatient settings, as well as to
      ensure the implementation of effective strategies and systems that increase the
      use of evidence-based therapies, in order to reduce the substantial HF morbidity
      and mortality risk.

PMID- 16955056
TI  - Congestion is an important diagnostic and therapeutic target in heart failure.
AB  - Most hospitalizations for acute heart failure syndrome (AHFS) are related to
      clinical congestion as a result of high left ventricular diastolic pressure
      (LVDP) rather than to low cardiac output. Patients frequently develop
      "hemodynamic congestion" (high LVDP) several days to weeks before the onset of
      symptoms and signs of clinical congestion. By the time symptoms and signs are
      evident, patients generally require hospitalization. High LVDP increases left
      ventricular (LV) wall stress and possibly contributes to neurohormonal activation
      and LV remodeling, thereby contributing to progression of heart failure (HF).
      Congestion is a major predictor of both morbidity and mortality in HF. Some
      methods may aid in the evaluation of silent hemodynamic congestion, but these
      assessment tools are generally underused. Identification of hemodynamic
      congestion, before the clinical manifestations appear, may potentially prevent
      hospitalization and slow the progression of HF by allowing life-saving
      interventions to be implemented sooner.

PMID- 16955057
TI  - Current approaches to monitoring and management of heart failure.
AB  - Decompensation in patients with congestive heart failure remains a treatment
      problem. Earlier detection of decompensation may result in a lessened need for
      hospitalization and perhaps an interruption of the as-yet-undetermined processes
      during decompensation that lead to an adverse effect on the natural history of
      heart failure. B-type natriuretic peptide is produced by right and/or left
      ventricular tissue in response to an increase in ventricular wall stress and may
      be used as an indicator of decompensation. New directions in monitoring now
      include novel device-based algorithms that determine either intraventricular
      pressure or intrathoracic impedance. When combined with clinical assessment,
      weight monitoring, and symptom assessment, these newer monitoring platforms may
      yield improvements in the natural history of heart failure.

PMID- 16955058
TI  - New approaches to monitoring heart failure before symptoms appear.
AB  - Intrathoracic impedance monitoring (approved by the US Food and Drug
      Administration) and implantable hemodynamic monitoring (IHM), which is under
      investigation, are promising techniques for the improved management of heart
      failure by detecting early changes in fluid status or hemodynamic congestion.
      Routine outpatient surveillance of intrathoracic impedance data from implanted
      devices may significantly reduce the currently high rates of hospital
      admission/readmission for patients with heart failure. IHM systems may extend
      such monitoring capabilities. Both emerging approaches for monitoring patients
      with heart failure may alert clinicians (and possibly patients) to impending
      decompensation before symptoms appear.

PMID- 16955059
TI  - Integrating device monitoring into the infrastructure and workflow of routine
      practice.
AB  - Monitoring strategies for patients with heart failure vary. Physical assessment
      and patient reporting are often unreliable and inconsistent. Continuous
      physiologic information from implanted devices identifies the progression to
      congestion in patients with chronic heart failure earlier in the process than
      traditional methods. Common themes of a successful system will require a means to
      provide device-based data to interested providers who then can interpret the
      information in the context of either remote or face-to-face clinical assessment.

PMID- 16955060
TI  - Integrating monitoring into the infrastructure and workflow of routine practice:
      OptiVol.
AB  - New cardiac resynchronization devices that monitor intrathoracic impedance may be
      utilized to monitor intravascular fluid status in chronic heart failure patients.
      Incorporating these devices into a heart failure medical practice requires the
      integration of heart failure medical services and electrophysiology. These
      devices must be interrogated and the data analyzed if the diagnostic information
      is to be useful in the care of heart failure patients. Device generated time
      aligned trends should be interpreted in the context of clinical findings. Systems
      must be well designed to deal with the results of solicited and unsolicited data.

PMID- 16955061
TI  - Case studies in advanced monitoring with the Chronicle device.
AB  - Three case studies illustrate the utility of advanced implantable hemodynamic
      monitors (IHMs). The cases include a 70-year-old with ischemic cardiomyopathy,
      chronic kidney disease, and recurrent volume overload; a 53-year-old with
      ischemic heart disease, mild effort-related angina, and New York Heart
      Association class III chronic heart failure; and a 21-year-old with severe
      dilated cardiomyopathy, all 3 patients having an IHM. The outcomes in these cases
      illustrate the capability of the IHM system for monitoring and detecting early
      changes in hemodynamic data and the use of these data to adjust medical therapies
      and reduce morbidity and risk of hospitalization. When pathologic hemodynamic
      changes are observed, this alerts the cardiologist to search for underlying
      causes, even when a patient on initial questioning denies any change in
      compliance or symptoms.

PMID- 16955063
TI  - Prognostic factors in prosthetic rehabilitation of bilateral dysvascular above
      knee amputee: is the stump condition an influencing factor?
AB  - AIM: The aim of this study was to evaluate the prognostic factors for
      rehabilitation outcome in bilateral dysvascular lower limb amputees, specifically
      to ascertain how the stump condition can influence the mobility outcome. METHODS:
      A retrospective study of 30 selected bilateral above-knee amputees for vascular
      disease was carried out. Barthel Index (BI) was given and stump condition was
      assessed at admission and at discharge. Influence of age, comorbidities and stump
      condition on effectiveness of BI was evaluated. Locomotor Capability Index (LCI)
      was performed at discharge. Influence of stump problems (pain, flexion, pain with
      flexion) on LCI was evaluated. RESULTS: At discharge, 25 patients were able to
      ambulate. Age and pathological conditions of stumps correlated negatively with BI
      effectiveness. LCI values were higher for patients with ideal stumps and lower
      for patients with combined stump pain and flexion deformities. Post hoc analysis
      showed that the principal factor negatively influencing the LCI score was the
      presence of stump flexion deformities. CONCLUSIONS: In our homogeneous group of
      bilateral amputees, age reduced the possibility of improving the level of
      autonomy. Good stump quality is one of the major determinants of mobility
      outcome. Efforts should be made to minimize stump complications. In particular,
      incorrect positioning of the stump, which is responsible for hip flexor
      retraction, should be avoided after surgery.

PMID- 16955064
TI  - Conservative treatment of thoracic outlet syndrome. A review of the literature.
AB  - Thoracic outlet syndrome (TOS) is a debated topic. While there are many clinical
      studies concerning the efficacy of surgical treatment, there are few regarding
      conservative treatment. It has not yet been established whether or not
      conservative treatment is effective and what the best treatment is. The aims of
      this study were to evaluate the efficacy of conservative treatment in TOS with
      particular reference to physiotherapy, orthotics, and taping and to make general
      recommendations for conservative treatment. The literature was reviewed. Medical
      databases consulted: Medline, Embase, CINAHL, Current Awareness, Pedro, Cochrane
      Library, Medscape. We used the following key words: thoracic outlet syndrome,
      double crush syndrome, entrapment, conservative, treatment, rehabilitation, and
      management. Languages of the articles reviewed: English, French, German, Spanish,
      Italian, and Portuguese. This analysis focussed on 10 studies of conservative
      treatment and 3 studies comparing the outcomes of conservative and surgical
      treatment, published from 1983 to 2001. This review found no randomised
      controlled trials, systematic reviews, or meta-analyses. Conservative treatment
      seems to be effective at reducing symptoms, improving function, and facilitating
      return to work, also when compared to surgery. We could not establish whether or
      not conservative treatment was better than no treatment or placebo, or what type
      of conservative treatment was the best.

PMID- 16955065
TI  - Efficacy of the symmetric, patient-oriented, rigid, three-dimensional, active
      (SPoRT) concept of bracing for scoliosis: a prospective study of the Sforzesco
      versus Lyon brace.
AB  - AIM: Bracing is considered to be effective in the treatment of adolescent
      idiopathic scoliosis. The concept prevailing today includes an asymmetrical
      construction, mainly using a mechanical three-point system. We developed the new
      Sforzesco brace, based on the SPoRT concept (Symmetric, Patient-oriented, Rigid,
      Three-dimensional, active). The aim of this study is to verify the results of
      this concept and brace, compared to three-point classical systems. METHODS: We
      performed a prospective, pair-controlled study. It was possible to match 15
      patients, out of the first 18 consecutively treated with the Sforzesco brace
      (Group SPoRT), with previous patients treated with the Lyon brace (Group LY).
      SPoRT included 14.2+/-1.7 year old patients, with 47+/-7 degrees Cobb worst
      curves, and 11+/-4 degrees Bunnell; LY included 13.6+/-1.6 year old patients,
      with 43+/-7 degrees Cobb and 12+/-5 degrees Bunnell. The brace had to be worn 23
      h per day and patients were evaluated after 6 months both clinically and
      radiographically (without the brace). Appropriate statistics were used. RESULTS:
      At the baseline there were slight differences between the groups, with SPoRT
      worse than LY. All radiographic and clinical parameters decreased significantly
      with treatment in both groups, apart from thoracic Cobb degrees in LY. SPoRT had
      better results than LY (P<0.05) radiographically (worst curve -10+/-5 degrees vs 
      5+/-7 degrees, all curves -8+/-7 degrees vs -6+/-7 degrees), for sagittal profile
      (distance from plumbline: T12 -6+/-9 mm vs +2+/-8 and L3 -7+/-12 vs 0+/-10) and
      aesthetics of the shoulders (9 improved and 6 unchanged vs 5 and 8) and waists
      (10 improved and 5 unchanged vs 5 and 8). Finally, clinical results in terms of
      patient recovery were better in SPoRT than LY (12 improved and 3 unchanged vs 8
      and 5). CONCLUSION: When a new treatment is introduced, it is not possible to
      wait years (end of therapy) before verifying its utility, and in scoliosis
      bracing a short term study already gives very important clues. This study
      confirms the immediate efficacy of brace treatment (even in such high degree
      cases) whatever the brace concept used, with only 2 (out of 30) progressed
      curves. In SPoRT we had no progressions, and obtained a statistically significant
      80% better radiographic results than LY in the worst scoliosis curve, and 40% in
      the average of all curves, as well as improved aesthetics and sagittal profile
      (that is crucial in scoliosis bracing). The Sforzesco brace should be used, and
      the SPoRT concept explored in the long term to verify if the classical three
      point system should be totally (or partially) abandoned.

PMID- 16955068
TI  - Anticancer activities of histone deacetylase inhibitors.
AB  - Histone deacetylases (HDACs) are enzymes involved in the remodelling of
      chromatin, and have a key role in the epigenetic regulation of gene expression.
      In addition, the activity of non-histone proteins can be regulated through HDAC
      mediated hypo-acetylation. In recent years, inhibition of HDACs has emerged as a
      potential strategy to reverse aberrant epigenetic changes associated with cancer,
      and several classes of HDAC inhibitors have been found to have potent and
      specific anticancer activities in preclinical studies. However, such studies have
      also indicated that the effects of HDAC inhibitors could be considerably broader
      and more complicated than originally understood. Here we summarize recent
      advances in the understanding of the molecular events that underlie the
      anticancer effects of HDAC inhibitors, and discuss how such information could be
      used in optimizing the development and application of these agents in the clinic,
      either as monotherapies or in combination with other anticancer drugs.

PMID- 16955067
TI  - NO-independent stimulators and activators of soluble guanylate cyclase: discovery
      and therapeutic potential.
AB  - Soluble guanylate cyclase (sGC) is a key signal-transduction enzyme activated by
      nitric oxide (NO). Impaired bioavailability and/or responsiveness to endogenous
      NO has been implicated in the pathogenesis of cardiovascular and other diseases.
      Current therapies that involve the use of organic nitrates and other NO donors
      have limitations, including non-specific interactions of NO with various
      biomolecules, lack of response and the development of tolerance following
      prolonged administration. Compounds that activate sGC in an NO-independent manner
      might therefore provide considerable therapeutic advantages. Here we review the
      discovery, biochemistry, pharmacology and clinical potential of haem-dependent
      sGC stimulators (including YC-1, BAY 41-2272, BAY 41-8543, CFM-1571 and A-350619)
      and haem-independent sGC activators (including BAY 58-2667 and HMR-1766).

PMID- 16955069
TI  - Targeting proteases: successes, failures and future prospects.
AB  - Until fairly recently, proteases were considered primarily to be protein
      degrading enzymes. However, this view has dramatically changed and proteases are
      now seen as extremely important signalling molecules that are involved in
      numerous vital processes. Protease signalling pathways are strictly regulated,
      and the dysregulation of protease activity can lead to pathologies such as
      cardiovascular and inflammatory diseases, cancer, osteoporosis and neurological
      disorders. Several small-molecule drugs targeting proteases are already on the
      market and many more are in development. The status of human protease research
      and prospects for future protease-targeted drugs are reviewed here, with
      reference to some key examples where protease drugs have succeeded or failed.

PMID- 16955070
TI  - Influence of the intensity, level and phase of spinal cord injury on the
      proliferation of T cells and T-cell-dependent antibody reactions in rats.
AB  - STUDY DESIGN: Three independent experiments in a rat model of contusive spinal
      cord (SC) injury were performed. Two studied the alterations induced by SC injury
      on some immunological aspects of the T-cell response. The third one evaluated the
      motor recovery of rats with low-thoracic injuries. OBJECTIVE: To examine the
      effect of level, intensity and phase of SC injury on T-cell proliferation and T
      cell-dependent antibody response. SETTING: Neuroimmunology Department, UIMEN,
      IMSS-CAMINA Research Center. METHODS: Lymphocyte proliferation and
      hemagglutination assays were performed. Animals were injured either moderately or
      severely at T1 or T12 SC segments. Analysis of peripheral T-cell proliferation in
      response to mitogens and to myelin basic protein (MBP), as well as of antibody
      production against a T-dependent antigen, was performed at acute, subacute and
      chronic phases. RESULTS: A significant decrease of both response to mitogens and
      antibody production was found especially during the acute phase and in animals
      with severe and high (T1)-level injury. Animals with low (T12) and moderate
      contusions recovered to control levels at the chronic phase. An autoimmune
      reaction against MBP was observed only in animals with severe contusion at low
      level. CONCLUSIONS: The intensity, level and phase of SC injury differentially
      alter the function of T cells. These results will allow a better interpretation
      of studies directed to elucidate the role of T lymphocytes in various processes
      developed after SC injury.

PMID- 16955071
TI  - Spontaneous recovery of hindlimb movement in completely spinal cord transected
      mice: a comparison of assessment methods and conditions.
AB  - STUDY DESIGN: To compare results obtained with a variety of locomotor rating
      scales in Th9/10 spinal cord transected (Tx) mice. OBJECTIVES: To assess
      spontaneous recovery with a variety of rating scales to find the most sensitive
      methods for assessing recovery levels in Tx mice and differences associated with
      gender and condition. SETTING: Laval University Medical Center, Neuroscience Unit
      & Laval University, Department of Anatomy and Physiology, Quebec City, Quebec,
      Canada. METHODS: Scales including the Basso, Beattie and Bresnahan (BBB), the
      Basso Mouse Score (BMS), the Antri, Orsal and Barthe (AOB), the Motor Function
      Score (MFS) and the Averaged Combined Score (ACOS) were used to assess, in open
      field and treadmill conditions, spontaneous locomotor recovery in male and female
      Tx mice. RESULTS: The ACOS scale revealed a progressive increase of spontaneous
      recovery during 5-weeks post-Tx. The other methods detected a progressive
      increase for the first 2-3 weeks post-Tx without any significant progress in
      weeks 4 and 5. Generally, scores obtained with each method were nonsignificantly
      different between males and females or between open-field and treadmill
      conditions. CONCLUSION: These results further confirm the existence of a limited
      but significant increase of locomotor function recovery, occurring without
      intervention, in Tx animals. Although each method could detect small levels of
      recovery, the ACOS method was discriminative enough to detect progressive changes
      up to 5 weeks post-Tx. In conclusion, the ACOS rating scale was the most
      discriminative method for assessing the spontaneous return of hindlimb movements
      found in Tx mice, both in open-field and treadmill conditions.

PMID- 16955072
TI  - International Spinal Cord Injury Data Sets.
AB  - STUDY DESIGN: Discussion and development of final consensus. OBJECTIVE: Present
      the background, purpose, and process for the International Spinal Cord Injury
      (SCI) Data Sets development. SETTING: International. METHODS: An international
      meeting on SCI data collection and analysis occurred at a workshop on May 2,
      2002, before the combined meeting of the American Spinal Injury Association
      (ASIA) and the International Spinal Cord Society (ISCoS) in Vancouver, British
      Columbia, Canada. At this meeting, a process was developed for selection of data
      elements to be included in International SCI Data Sets. RESULTS: An overall
      structure and terminology has been developed following the format of the
      International Classification of Functioning, Disability and Health (ICF). This
      includes definitions of the Core Data Set, as well as Modules with Basic
      Questions or Data Sets and Expanded Data Sets. The Core Data Set has been
      developed and will be presented separately. Working groups for additional modules
      are being established as well as general guidelines for the development of the
      modules. CONCLUSION: The presented format should help in developing data sets and
      modules within various topics related to SCI.

PMID- 16955073
TI  - International Spinal Cord Injury Core Data Set.
AB  - STUDY DESIGN: Survey of expert opinion, feedback, and development of final
      consensus. OBJECTIVE: Present the background, purpose, development process, and
      results for the International Spinal Cord Injury (SCI) Core Data Set. SETTING:
      International. METHODS: A committee of experts was established to select and
      define data elements to be included in an International SCI Core Data Set. A
      draft core data set was developed and disseminated to appropriate organisations
      for comment. All suggested revisions were considered, and a final version of the
      core data set was disseminated again for approval and adoption. RESULTS: The core
      data set consists of 24 variables, including basic demographic characteristics,
      dates of admission and discharge from initial acute and rehabilitation care,
      cause of injury, place of discharge, presence of vertebral fractures and
      associated injuries, occurrence of spinal surgery, and measures of neurological
      and ventilator status. CONCLUSION: Collection of the core data set should be a
      basic ingredient of all future studies of SCI to facilitate accurate description
      of patient populations and comparison of results across published studies from
      around the world.

PMID- 16955074
TI  - Developing core sets for persons with spinal cord injuries based on the
      International Classification of Functioning, Disability and Health as a way to
      specify functioning.
AB  - OBJECTIVE: The objective of this paper is to outline the proposed development
      process for the ICF Core Sets for Spinal Cord Injury (SCI) and to invite clinical
      and consumer experts to actively participate in this process. ICF Core Sets are
      selections of categories of the International Classification of Functioning,
      Disability and Health (ICF) that are relevant to persons with a specific
      condition or in a specific setting. METHOD: The project is a cooperation between
      the ICF Research Branch of the World Health Organization (WHO) Collaboration
      Centre of the Family of International Classifications (DIMDI, Germany), the
      Classification, Assessment and Terminology (CAT) team and the Disability and
      Rehabilitation (DAR) team at WHO, the International Spinal Cord Society (ISCoS)
      and International Society for Physical and Rehabilitation Medicine (ISPRM) and
      partner institutions across the world. The project will consist of four worldwide
      studies to be conducted from 2006 to 2007 with a proposed ICF Core Set Consensus
      Conference to be held in 2007. ICF categories relevant for SCI are to be
      identified by means of (I) an empirical study, (II) a systematic review of
      outcomes and measures used in SCI research (III) an expert survey and (IV) focus
      groups and semistructured interviews with persons with SCI. Consensus about items
      that have to be part of a Comprehensive and of a Brief ICF Core Set for SCI will
      be reached in a final ICF Core Set Consensus Conference. Subsequent field testing
      will be necessary to validate this first version of ICF Core Sets for SCI.
      INVITATION FOR PARTICIPATION: The development of ICF Core Sets is an inclusive
      and open process. Anyone who wishes to actively participate in this process is
      invited to contact the project coordinator (Monika.Scheuringer@med.uni
      muenchen.de or http://www.icf-research-branch.org/research/spinalcord
      injuries.htm). Individuals, institutions and associations can be formally
      associated as partners of the project.

PMID- 16955075
TI  - The replication clamp-loading machine at work in the three domains of life.
AB  - Sliding clamps are ring-shaped proteins that tether DNA polymerases to DNA, which
      enables the rapid and processive synthesis of both leading and lagging strands at
      the replication fork. The clamp-loading machinery must repeatedly load sliding
      clamp factors onto primed sites at the replication fork. Recent structural and
      biochemical analyses provide unique insights into how these clamp-loading ATPase
      machines function to load clamps onto the DNA. Moreover, these studies highlight
      the evolutionary conservation of the clamp-loading process in the three domains
      of life.

PMID- 16955076
TI  - Do we underestimate the importance of water in cell biology?
AB  - Liquid water is a highly versatile material. Although it is formed from the
      tiniest of molecules, it can shape and control biomolecules. The hydrogen-bonding
      properties of water are crucial to this versatility, as they allow water to
      execute an intricate three-dimensional 'ballet', exchanging partners while
      retaining complex order and enduring effects. Water can generate small active
      clusters and macroscopic assemblies, which can both transmit information on
      different scales.

PMID- 16955077
TI  - Protein SUMOylation is massively increased in hibernation torpor and is critical
      for the cytoprotection provided by ischemic preconditioning and hypothermia in
      SHSY5Y cells.
AB  - Hibernation torpor provides an excellent natural model of tolerance to profound
      reductions in blood flow to the brain and other organs. Here, we report that
      during torpor of 13-lined ground squirrels, massive SUMOylation occurs in the
      brain, liver, and kidney. The level of small ubiquitin-related modifier (SUMO)
      conjugation coincides with the expression level of Ubc9, the SUMO specific E2
      conjugating enzyme. Hypothermia alone also increased SUMO conjugation, but not as
      markedly as hibernation torpor. Increased SUMO conjugation (induced by Ubc9
      overexpression, ischemic preconditioning (PC)+/-hypothermia) was necessary and
      sufficient for tolerance of SHSY5Y neuroblastoma cells to oxygen/glucose
      deprivation (OGD) ('in vitro ischemia'); decreased SUMO conjugation (induced by a
      dominant-negative Ubc9) severely reduced tolerance to OGD in these cells. These
      data indicate that post-translational modification of proteins by SUMOylation is
      a prominent feature of hibernation torpor and is critical for cytoprotection by
      ischemic PC+/-hypothermia in SHSY5Y cells subjected to OGD.

PMID- 16955078
TI  - Alterations in mammalian target of rapamycin signaling pathways after traumatic
      brain injury.
AB  - In response to traumatic brain injury (TBI), neurons initiate neuroplastic
      processes through the activation of intracellular signaling pathways. However,
      the molecular mechanisms underlying neuroplasticity after TBI are poorly
      understood. To study this, we utilized the fluid-percussion brain injury (FPI)
      model to investigate alterations in the mammalian target of rapamycin (mTOR)
      signaling pathways in response to TBI. Mammalian target of rapamycin stimulates
      mRNA translation through phosphorylation of eukaryotic initiation factor 4E
      binding protein-1 (4E-BP1), p70 ribosomal S6 kinase (p70S6K), and ribosomal
      protein S6 (rpS6). These pathways coordinate cell growth and neuroplasticity via
      dendritic protein synthesis. Rats received sham surgery or moderate parasagittal
      FPI on the right side of the parietal cortex, followed by 15 mins, 30 mins, 4 h,
      24 h, or 72 h of recovery. Using Western blot analysis, we found that mTOR,
      p70S6K, rpS6, and 4E-BP1 phosphorylation levels were significantly increased in
      the ipsilateral parietal cortex and hippocampus from 30 mins to 24 h after TBI,
      whereas total protein levels were unchanged. Using confocal microscopy to
      localize these changes, we found that rpS6 phosphorylation was increased in the
      parietal cortex and all subregions of the hippocampus. In accordance with these
      results, eIF4E, a key, rate-limiting mRNA translation factor, was also
      phosphorylated by mitogen-activated protein kinase-interacting kinase 1 (Mnk1) 15
      mins after TBI. Together, these results suggest that changes in mRNA translation
      may be one mechanism that neurons use to respond to trauma and may contribute to
      the neuroplastic changes observed after TBI.

PMID- 16955079
TI  - Radiation therapy and biologics: a ripe opportunity?

PMID- 16955080
TI  - Are we taking the right approach in planning chemoprevention studies?

PMID- 16955081
TI  - It's time to accept that intake of dairy foods is not related to risk of ovarian
      cancer.

PMID- 16955082
TI  - Intravesical bacillus Calmette-Guerin combined with electromotive mitomycin for
      high-risk superficial bladder cancer.

PMID- 16955083
TI  - Advanced non-small-cell lung cancer: 'triplets' better than 'doublets'?

PMID- 16955084
TI  - Do statins prevent cancer?

PMID- 16955085
TI  - Does chemotherapy given directly to the liver improve survival in patients with
      hepatic metastasis?

PMID- 16955086
TI  - Can a point-of-care urine protein assay monitor bladder cancer recurrence?

PMID- 16955087
TI  - Multimodality therapy for Pancoast tumor.
AB  - The management of Pancoast tumors has challenged surgeons and radiation and
      medical oncologists over several decades. Retrospective studies have raised a
      greater awareness of the importance of positive N2 lymph nodes in terms of
      prognosis and treatment decision making. While patients with positive N2 lymph
      nodes have generally been excluded from trials of preoperative chemoradiation for
      superior sulcus tumors, the potential of surgery for these patients is still
      being evaluated. The role of PET for initial staging as well as for assessment of
      disease response to induction therapy continues to evolve. The use of combined
      treatment modalities has enhanced the progress in successfully treating Pancoast
      tumors. The historical data showing improved results with a combination of
      surgery and radiation compared with surgery alone for patients with positive N2
      nodes provides the basis for several important clinical trials that integrate the
      use of chemotherapy into the treatment paradigm. The Southwest Oncology Group and
      Japanese Clinical Oncology Group have shown dramatic improvements in complete
      resection rates following a neoadjuvant course of combined chemotherapy and
      radiation therapy compared with historical series. We discuss relevant ongoing
      clinical trials that include consolidative taxane-based chemotherapy and the role
      of prophylactic cranial irradiation in complete responders. Future potential
      areas of investigation, including the role of surgery for patients with N2
      positive disease and the use of imaging to assess response after induction
      therapy, are discussed.

PMID- 16955088
TI  - Sedation for the care of patients with advanced cancer.
AB  - Sedation in the context of palliative medicine is the monitored use of
      medications to induce varying degrees of unconsciousness to bring about a state
      of decreased or absent awareness (i.e. unconsciousness) in order to relieve the
      burden of otherwise intractable suffering. Sedation is used in palliative care in
      several settings: transient controlled sedation, sedation in the management of
      refractory symptoms at the end of life, emergency sedation, respite sedation, and
      sedation for refractory psychological or existential suffering. Sedation is
      controversial in that it diminishes the capacity of the patient to interact,
      function, and, in some cases, live. There is no distinct ethical problem in the
      use of sedation to relieve otherwise intolerable suffering in patients who are
      dying. Since all medical treatments involve risks and benefits, each potential
      option must be evaluated for its promise with regards to achieving the goals of
      care. When risks of treatment are involved, to be justified these risks must be
      proportionate to the gravity of the clinical indication. Some aspects of
      management, such as the need for hydration in patients undergoing sedation and
      the use of sedation in the management of psychological and spiritual suffering,
      remain controversial.

PMID- 16955089
TI  - Technology Insight: tuning into the genetic orchestra using microarrays-
      limitations of DNA microarrays in clinical practice.
AB  - Scientific advances in the field of genetics and gene-expression profiling have
      revolutionized the concept of patient-tailored treatment. Analysis of
      differential gene-expression patterns across thousands of biological samples in a
      single experiment (as opposed to hundreds to thousands of experiments measuring
      the expression of one gene at a time), and extrapolation of these data to answer
      clinically pertinent questions such as those relating to tumor metastatic
      potential, can help define the best therapeutic regimens for particular patient
      subgroups. The use of microarrays provides a powerful technology, allowing in
      depth analysis of gene-expression profiles. Currently, microarray technology is
      in a transition phase whereby scientific information is beginning to guide
      clinical practice decisions. Before microarrays qualify as a useful clinical
      tool, however, they must demonstrate reliability and reproducibility. The high
      throughput nature of microarray experiments imposes numerous limitations, which
      apply to simple issues such as sample acquisition and data mining, to more
      controversial issues that relate to the methods of biostatistical analysis
      required to analyze the enormous quantities of data obtained. Methods for
      validating proposed gene-expression profiles and those for improving trial
      designs represent some of the recommendations that have been suggested. This
      Review focuses on the limitations of microarray analysis that are continuously
      being recognized, and discusses how these limitations are being addressed.

PMID- 16955090
TI  - High-risk melanoma with nodal involvement in a young woman.
AB  - BACKGROUND: An 18-year-old female presented to her General Practitioner with a
      bleeding mole on her back. The mole had been present since childhood but had
      started to bleed in the past month. She was otherwise asymptomatic with no
      relevant previous medical history. Physical examination revealed a 1.5 cm 1.7 cm
      pigmented lesion on the left aspect of the patient's upper back. There was no
      palpable lymphadenopathy. INVESTIGATIONS: Physical examination, excision biopsy,
      sentinel lymph node biopsy, CT scan of chest, abdomen and pelvis. DIAGNOSIS:
      Stage IIIB (T3bN2aM0) focally ulcerated, nodular malignant melanoma (Breslow
      depth 2.5 mm, Clark's level IV). MANAGEMENT: Wide re-excision, completion
      dissection of the left axillary lymph node, adjuvant high-dose interferon with
      maintenance interferon.

PMID- 16955091
TI  - Smoking, cereal consumption, and supplementation affect cadmium content in breast
      milk.
AB  - Breast milk might be a source of potentially toxic metals such as cadmium (Cd).
      The purpose of the present study is to provide data pertaining to the influence
      of maternal lifestyles on Cd concentrations in breast milk in the Austrian
      setting. Breast milk was obtained from 124 Austrian women. Each participant
      provided 10 ml of milk. A second group of eight mothers were recruited to
      investigate changes in their milk cadmium levels at 1, 3, 5, 7 and 9 weeks post
      partum. The study participants filled a questionnaire concerning nutrition,
      supplementation, and smoking habits. The samples were analyzed using GF-Atomic
      Absorption Spectrophotometer (AAS). The mean Cd content in breast milk was among
      the lowest in Europe (0.086 +/- 0.085 microg/l, 95% CI: 0.07-0.10; n = 124).
      Increased Cd levels in breast milk were found to be significantly associated with
      frequent cereal consumption and smoking. Smokers had a two-fold higher
      concentration than did non-smokers (0.15 versus 0.07 microg/l; P = 0.000). In
      contrast, low Cd levels in breast milk were associated with the intake of
      supplements containing trace elements or vitamins and trace elements (P < 0.05).
      This protective effect of supplements on Cd levels was only observed in non
      smokers. The Cd levels registered in the present investigation were far below
      critical levels. We conclude that the current maternal Cd levels in Austria
      signify no risk for the breastfed infant of a healthy mother. Further research
      will have to focus on the specific effects of supplementation and smoking on Cd
      concentrations.

PMID- 16955092
TI  - All aboard for graduate school.
AB  - Graduate school can be an intimidating journey to undertake. Luckily, there are
      plenty of sources of advice to help you on the way.

PMID- 16955093
TI  - L(ou)sy miRNA targets?

PMID- 16955094
TI  - How GPCRs hit the switch.

PMID- 16955095
TI  - Small interfering RNAs to the rescue: blocking L1 retrotransposition.

PMID- 16955096
TI  - RNase II structure completes group portrait of 3' exoribonucleases.

PMID- 16955099
TI  - Artery calcification in uremic rats is increased by a low protein diet and
      prevented by treatment with ibandronate.
AB  - The present experiments investigate medial artery calcification in adult rats
      made uremic by feeding a synthetic diet containing 0.75% adenine for 4 weeks.
      Calcification was assessed by Alizarin red staining of intact aortas, by von
      Kossa staining of carotid artery sections, and by calcium and phosphate
      incorporated into the thoracic aorta. The major conclusions are as follows:
      Lowering the protein content of the diet from 25 to 2.5% dramatically increases
      the frequency and extent of medial artery calcification in uremic rats without
      significantly affecting the elevation in serum creatinine, phosphate, or
      parathyroid hormone. This observation suggests that low dietary protein intake
      could be a risk factor for medial artery calcification in uremic patients. Medial
      artery calcification in uremic rats is prevented by a dose of ibandronate that
      inhibits bone resorption. The observation suggests that bone resorption
      inhibitors could prevent artery calcification in uremic patients. Medial artery
      calcification in uremic rats correlates with increased serum bone Gla protein
      (BGP; osteocalcin), but not with serum matrix Gla protein or fetuin. This finding
      indicates that it could be of interest to examine the relation between serum BGP
      and artery calcification in uremic patients. Each of these conclusions lends
      support for our hypothesis that medial artery calcification is linked to bone
      resorption. Future investigations of the as yet unknown biochemical basis for
      this link will be facilitated by the present discovery that a synthetic, 2.5%
      protein diet containing 0.75% adenine produces consistent and dramatic medial
      calcification in adult rats within just 4 weeks.

PMID- 16955100
TI  - Lipotoxicity.
AB  - Excess fatty acids accompanied by triglyceride accumulation in parenchymal cells
      of multiple tissues including skeletal and cardiac myocytes, hepatocytes, and
      pancreatic beta cells results in chronic cellular dysfunction and injury. The
      process, now termed lipotoxicity, can account for many manifestations of the
      'metabolic syndrome'. Most data suggest that the triglycerides serve primarily a
      storage function with toxicity deriving mainly from long-chain nonesterified
      fatty acids (NEFA) and their products such as ceramides and diacylglycerols. In
      the kidney, filtered NEFA carried on albumin can aggravate the chronic tubule
      damage and inflammatory phenotype that develop during proteinuric states and
      lipid loading of both glomerular and tubular cells is a common response to renal
      injury that contributes to progression of nephropathy. NEFA-induced mitochondrial
      dysfunction is the primary mechanism for energetic failure of proximal tubules
      during hypoxia/reoxygenation and persistent increases of tubule cell NEFA and
      triglycerides occur during acute renal failure in vivo in association with
      downregulation of mitochondrial and peroxisomal enzymes of beta oxidation. In
      acute renal failure models, peroxisome proliferator-activated receptor alpha
      ligand treatment can ameliorate the NEFA and triglyceride accumulation and limits
      tissue injury likely via both direct tubule actions and anti-inflammatory
      effects. Both acute and chronic kidney disease are associated with systemic
      manifestations of the metabolic syndrome.

PMID- 16955101
TI  - Calcineurin-inhibitor induced pain syndrome after organ transplantation.

PMID- 16955102
TI  - Acute sodium overload produces renal tubulointerstitial inflammation in normal
      rats.
AB  - The aim of the present study was to determine whether acute sodium overload could
      trigger an inflammatory reaction in the tubulointerstitial (TI) compartment in
      normal rats. Four groups of Sprague-Dawley rats received increasing NaCl
      concentrations by intravenous infusion. Control (C): Na+ 0.15 M; G1: Na+ 0.5 M;
      G2: Na+ 1.0 M; and G3: Na+ 1.5 M. Creatinine clearance, mean arterial pressure
      (MAP), renal blood flow (RBF), and sodium fractional excretion were determined.
      Transforming growth factor beta1 (TGF-beta1), alpha-smooth muscle actin (alpha
      SMA), RANTES, transcription factor nuclear factor-kappa B (NF-kappaB), and
      angiotensin II (ANG II) were evaluated in kidneys by immunohistochemistry.
      Animals with NaCl overload showed normal glomerular function without MAP and RBF
      modifications and exhibited a concentration-dependent natriuretic response.
      Plasmatic sodium increased in G2 (P < 0.01) and G3 (P < 0.001). Light microscopy
      did not show renal morphological damage. Immunohistochemistry revealed an
      increased number of ANG II-positive tubular cells in G2 and G3, and positive
      immunostaining for NF-kappaB only in G3 (P < 0.01). Increased staining of alpha
      SMA in the interstitium (P < 0.01), TGF-beta1 in tubular cells (P < 0.01), and a
      significant percentage (P < 0.01) of positive immunostaining for RANTES in
      tubular epithelium and in glomerular and peritubular endothelium were detected in
      G3 > G2 > C group. These results suggest that an acute sodium overload is able
      'per se' to initiate TI endothelial inflammatory reaction (glomerular and
      peritubular) and incipient fibrosis in normal rats, independently of hemodynamic
      modifications. Furthermore, these findings are consistent with the possibility
      that activation of NF-kappaB and local ANG II may be involved in the pathway of
      this inflammatory process.

PMID- 16955103
TI  - Nephrin loss in experimental diabetic nephropathy is prevented by deletion of
      protein kinase C alpha signaling in-vivo.
AB  - Albuminuria in diabetic nephropathy is due to endothelial dysfunction, a loss of
      negative charges in the basement membrane, and changes a of the slit-membrane
      diaphragm composition. We have recently shown that protein kinase C alpha
      (PKCalpha)-deficient mice are protected against the development of albuminuria
      under diabetic conditions. We here tested the hypothesis that PKCalpha mediates
      the hyperglycemia-induced downregulation of the slit-diaphragm protein nephrin.
      After 8 weeks of streptozotocin (STZ)-induced hyperglycemia the expression of
      glomerular nephrin was significantly reduced. In contrast, other slit-diaphragm
      proteins such as podocin and CD2AP were unaltered in diabetic state. In PKCalpha
      /- mice, hyperglycemia-induced downregulation of nephrin was prevented. Podocin
      and CD2AP remained unchanged. In addition, the nephrin messenger RNA expression
      was also reduced in hyperglycemic wild-type mice but remained unaltered in
      PKCalpha-/- mice. We postulate that the underlying mechanism of the hyperglycemia
      induced regulation of various proteins of the glomerular filtration barrier is a
      PKCalpha-dependent regulation of the Wilms' Tumor Suppressor (WT1) which
      previously has been shown to act as a direct transcription factor on the nephrin
      promoter. Our data suggest that PKCalpha activation may be an important
      intracellular signaling pathway in the regulation of nephrin expression and
      glomerular albumin permeability in the diabetic state.

PMID- 16955104
TI  - Correlation of simple imaging tests and coronary artery calcium measured by
      computed tomography in hemodialysis patients.
AB  - Vascular calcification is associated with an adverse prognosis in end-stage renal
      disease. It can be accurately quantitated with computed tomography but simple in
      office techniques may provide equally useful information. Accordingly we compared
      the results obtained with simple non-invasive techniques with those obtained
      using electron beam tomography (EBT) for coronary artery calcium scoring (CACS)
      in 140 prevalent hemodialysis patients. All patients underwent EBT imaging, a
      lateral X-ray of the lumbar abdominal aorta, an echocardiogram, and measurement
      of pulse pressure (PP). Calcification of the abdominal aorta was
      semiquantitatively estimated with a score (Xr-score) of 0-24 divided into
      tertiles, echocardiograms were graded as 0-2 for absence or presence of
      calcification of the mitral and aortic valve and PP was divided in quartiles. The
      CACS was elevated (mean 910+/-1657, median 220). The sensitivity and specificity
      for CACS > or = 100 was 53 and 70%, for calcification of either valve and 67 and
      91%, respectively, for Xr-score > or = 7. The area under the curve for CACS > or
      = 100 associated with valve calcification and Xr-score was 0.62 and 0.78,
      respectively. The likelihood ratio (95% confidence interval) of CACS > or = 100
      was 1.79 (1.09, 2.96) for calcification of either valve and 7.50 (2.89, 19.5) for
      participants with an Xr-score > or = 7. In contrast, no association was present
      between PP and CACS. In conclusion, simple measures of cardiovascular
      calcification showed a very good correlation with more sophisticated measurements
      obtained with EBT. These methodologies may prove very useful for in-office
      imaging to guide further therapeutic choices in hemodialysis patients.

PMID- 16955105
TI  - Proximal tubular handling of phosphate: A molecular perspective.
AB  - Members of the SLC34 gene family of solute carriers encode for three Na+
      dependent phosphate (P i) cotransporter proteins, two of which (NaPi-IIa/SLC34A1
      and NaPi-IIc/SLC34A3) control renal reabsorption of P i in the proximal tubule of
      mammals, whereas NaPi-IIb/SCLC34A2 mediates P i transport in organs other than
      the kidney. The P i transport mechanism has been extensively studied in
      heterologous expression systems and structure-function studies have begun to
      reveal the intricacies of the transport cycle at the molecular level using
      techniques such as cysteine scanning mutagenesis, and voltage clamp fluorometry.
      Moreover, sequence differences between the three types of cotransporters have
      been exploited to obtain information about the molecular determinants of hormonal
      sensitivity and electrogenicity. Renal handling of P i is regulated by hormonal
      and non-hormonal factors. Changes in urinary excretion of P i are almost
      invariably mirrored by changes in the apical expression of NaPi-IIa and NaPi-IIc
      in proximal tubules. Therefore, understanding the mechanisms that control the
      apical expression of NaPi-IIa and NaPi-IIc as well as their functional properties
      is critical to understanding how an organism achieves P i homeostasis.

PMID- 16955106
TI  - Adequacy of automated peritoneal dialysis with and without manual daytime
      exchange: A randomized controlled trial.
AB  - Until now, it remains unclear whether the addition of manual daytime exchanges or
      increasing the nightly dialysate flow is the best strategy to optimize automated
      peritoneal dialysis (APD) treatment. In this open-label randomized controlled
      crossover trial, 18 patients with high-average (HA) or low-average (LA)
      peritoneal transport rates sequentially underwent two different APD regimens for
      7 days each, with an intermittent washout period of 7 days. 'Manual exchange'
      treatment was a conventional APD with low nightly dialysate flow and one manual
      daytime exchange. 'High-flow' treatment was defined by cycler therapy with high
      dialysate flow but without manual daytime exchange. Creatinine clearances (8.56+/
      1.22 vs 7.87+/-1.04 l/treatment, P = 0.011) and urea nitrogen clearances (12.83+/
      1.98 vs 11.68+/-1.06 l/treatment, P = 0.014) were significantly increased during
      'high-flow' treatment compared to 'manual exchange' treatment. Sodium removal was
      significantly lower and glucose absorption was higher with the 'high-flow'
      regimen. Phosphate clearances, beta2-microglobulin clearances, ultrafiltration,
      and peritoneal protein loss were not different between the two treatment
      modalities. Subgroup analysis dependent on peritoneal transport types showed that
      the effect on clearances was most marked and significant in HA transporters,
      whereas sodium removal was lowest in LA transporters. We conclude that small
      solute clearances can be significantly improved and middle molecule clearances
      maintained in APD patients by increasing the nightly dialysate flow instead of
      adding a manual daytime exchange. However, the possible benefit of better
      clearances with higher nightly treatment volumes has to be weighed against
      increased costs and the possible negative impact of impaired sodium removal,
      especially in LA transporters.

PMID- 16955107
TI  - Clearance and removal of oxalate in children on intensified dialysis for primary
      hyperoxaluria type 1.
AB  - Patients with end-stage renal failure owing to primary hyperoxaluria type 1 (PH1)
      receive dialysis while waiting for transplantation. So far, dialysis has not been
      shown to overcome the problem of ongoing oxalate production and deposition at
      extrarenal sites. We report on six children with PH1 who had to be dialyzed for a
      median period of 2.5 years while awaiting liver transplantation. Aiming at
      preventing oxalate tissue accretion, oxalate mass transfer was studied and
      dialysis intensified accordingly. Mean plasma oxalate concentration was between
      51 and 137 micromol/l. In three of the six patients with a urinary output between
      630 and 3140 ml, urinary removal of oxalate was between 5.6 and 12.4
      mmol/week/1.73 m2. Hemodialysis (HD) in five of the six patients demonstrated a
      mean oxalate dialysance between 158 and 444 l/week/1.73 m2. Peritoneal dialysis
      (PD) in two of the six patients showed mean oxalate clearances of 66 and 103
      l/week/1.73 m2. One patient received HD and PD. By adding all modes of
      elimination, a mean total oxalate mass between 10.1 and 24.1 mmol/week/1.73 m2
      was removed. Dialysis is still necessary as a temporary therapy for a number of
      patients with PH1. Dialysis should be instituted pre-emptively and maximally
      exploited by intensified HD/PD treatment protocols, without, however, cutting
      back urinary output.

PMID- 16955108
TI  - Glomerular volume and renal histology in obese and non-obese living kidney
      donors.
AB  - The link between obesity and renal disease is unclear, and there is no consensus
      as to whether obese individuals are at increased risk for kidney disease after
      living kidney donation if they otherwise meet acceptance criteria. We
      retrospectively studied time-zero (implantation) biopsies in 49 obese (body mass
      index (BMI) > or = 30 kg/m2) and 41 non-obese (BMI < 30 kg/m2) renal donors that
      met acceptance criteria. We found that our obese donor population had higher
      systolic blood pressure (P < 0.001 vs non-obese) and higher absolute iothalamate
      clearance (P = 0.001 vs non-obese) before donation. The obese donors had larger
      glomerular planar surface area compared to non-obese controls (P = 0.017), and
      this parameter correlated with patient weight and urinary microalbumin excretion.
      Detailed examination of the biopsies revealed that although most histologic
      findings were similar between groups, the obese donors had more tubular dilation
      (P = 0.01), but less tubular vacuolization (P = 0.02) than the non-obese
      controls. There was also a trend toward more arterial hyalinosis in the obese
      patients than controls (P = 0.08). From these data, our studies detected subtle
      differences in donor organs obtained from obese compared to non-obese
      individuals. Further studies should be carried out to quantify the long-term
      impact of these findings.

PMID- 16955109
TI  - Meeting report on the Bellagio Conference 'prevention of vascular diseases in the
      emerging world: An approach to global health equity'.
AB  - Representatives from five international organizations (International Society of
      Nephrology, World Heart Federation, International Diabetes Federation,
      International Atherosclerosis Federation, and International Society of
      Hypertension) participated in a strategic planning workshop in December 2005 in
      Bellagio, Italy sponsored by the Rockefeller Foundation. There were equal
      representatives from developed and developing countries. Global perspectives on
      diabetes and cardiovascular and renal diseases were presented, with special
      emphasis on China, India, Latin America, and Africa. The rationale and
      effectiveness of preventive measures were discussed. It was apparent that
      measures for primary prevention and early intervention for all the chronic
      vascular diseases are similar. The five organizations agreed that an integrated
      global approach to chronic vascular diseases is needed. They resolved to
      collaborate and work towards an integrated approach to chronic vascular diseases
      with the establishment of a 5-year plan for the prevention and treatment of
      chronic vascular diseases, including public advocacy, advising international and
      national agencies, and improving education and the practice of established
      approaches.

PMID- 16955110
TI  - Tunneled catheters' outcome optimization among diabetics on dialysis through
      antibiotic-lock placement.
AB  - Efficacy and safety of antibiotic 'locks', in prevention of thrombotic and
      infectious complication-related morbidity and mortality, among diabetics dialyzed
      through tunneled-cuffed catheters (TCCs) has not been effectively investigated.
      This trial was designed to investigate the outcome of TCCs (n = 109), inserted
      among 96 diabetic end-stage renal disease patients (March 2002-February 2003), by
      comparing the catheter thrombosis, catheter-related bloodstream infections
      (CRBSI), catheter survival, and mortality rates, between the cohorts of 49
      patients who had TCCs (n = 51) 'locked' with cefotaxime/heparin (group I) and 47
      patients with TCCs (n = 58) filled with standard heparin (group II). Thrombosis
      was defined as the inability to use catheter at a blood flow of 200 ml/min
      despite intraluminal thrombolysis. Primary end points were catheter thrombosis
      and CRBSI; elective catheter removal and CRBSI-related death led to sensor of
      TCCs follow-up. Patients with intraluminal cefotaxime/heparin lock, on cumulative
      survival analysis, showed a superior thrombosis-free (86.3 vs 63.8%, P = 0.023,
      log rank), infection-free (72.9 vs 27.1%, P = 0.004, log rank), and thrombosis-
      and infection-free TCC survival (78.4 vs 37.9%, P = 0.001, log rank) at 365 days,
      besides having significantly lower incidence of CRBSI (1.56 vs 3.68 episodes/1000
      catheter days, P < 0.0001) and CRBSI-related mortality (9.8 vs 23.4%, P = 0.015),
      compared with the heparin-alone group. Deployment of cefotaxime-heparin 'lock'
      enhances catheter survival; reduces thrombotic and infectious complications and
      ensuing mortality, among diabetics on dialysis. However, further studies are
      needed to define the long-term implications of antibiotic locks in terms of the
      risk of emergence of antimicrobial resistance.

PMID- 16955111
TI  - Albumin induces endoplasmic reticulum stress and apoptosis in renal proximal
      tubular cells.
AB  - Chronic proteinuria appears to be a key factor in tubulointerstitial damage.
      Recent studies have emphasized a pathogenic role of endoplasmic reticulum (ER)
      stress which is induced by the accumulation of misfolded proteins in ER,
      extracellular stress, etc. In the present study, we investigated ER stress and ER
      stress-induced apoptosis in proximal tubular cells (PTCs). Immortalized rat PTCs
      (IRPTCs) were cultured with bovine serum albumin (BSA). The viability of IRPTCs
      decreased proportionately with BSA overload in a time-dependent manner.
      Quantitative real-time polymerase chain reaction analysis revealed that 40 mg/ml
      BSA increases mRNA of ER stress markers by 7.7- and 4.6-fold (glucose-regulated
      protein 78 (GRP78) and oxygen-regulated protein 150 (ORP150), respectively) as
      compared to control. The increased expression of ORP150 and GRP78 in IRPTCs with
      albumin overload was detected by Western blot and immunofluorescence study. These
      in vitro observations were supported by in vivo studies, which demonstrated that
      ER stress proteins were upregulated at PTCs in experimental proteinuric rats.
      Furthermore, increased ER stress-induced apoptosis and activation of caspase-12
      were observed in IRPTCs with albumin overload and kidneys of experimental
      proteinuric rats. We confirmed that apoptotic cell death was attenuated by co
      incubation with caspase-3 inhibitor or calpain inhibitors. These results indicate
      that the ER stress-induced apoptosis pathway contributed to the insult of tubular
      cells by proteinuria. In conclusion, renal tubular cells exposed to high protein
      load suffer from ER stress. ER stress may subsequently lead to tubular damage by
      activation of caspase-12.

PMID- 16955112
TI  - Mapping phenotypic plasticity and genotype-environment interactions affecting
      life-history traits in Caenorhabditis elegans.
AB  - Phenotypic plasticity and genotype-environment interactions (GEI) play an
      important role in the evolution of life histories. Knowledge of the molecular
      genetic basis of plasticity and GEI provides insight into the underlying
      mechanisms of life-history changes in different environments. We used a
      genomewide single-nucleotide polymorphism map in a recombinant N2 x CB4856 inbred
      panel of the nematode Caenorhabditis elegans to study the genetic control of
      phenotypic plasticity to temperature in four fitness-related traits, that is, age
      at maturity, fertility, egg size and growth rate. We mapped quantitative trait
      loci (QTL) for the respective traits at 12 and 24 degrees C, as well as their
      plasticities. We found genetic variation and GEI for age at maturity, fertility,
      egg size and growth rate. GEI in fertility and egg size was attributed to changes
      in rank order of reaction norms. In case of age at maturity and growth rate, GEI
      was caused mainly by differences in the among-line variance. In total, 11 QTLs
      were detected, five QTL at 12 degrees C and six QTL at 24 degrees C, which were
      associated with life-history traits. Five QTL associated with age at maturity,
      fertility and growth rate showed QTL x environment interaction. These colocalized
      with plasticity QTL for the respective traits suggesting allelic sensitivity to
      temperature. Further fine mapping, complementation analyses and gene silencing
      are planned to identify candidate genes underlying phenotypic plasticity for age
      at maturity, fertility and growth.

PMID- 16955113
TI  - An unusual phylogeography in the bushcricket Ephippiger ephippiger from Southern
      France.
AB  - Pleistocene glaciations have played a major role in species divergence. The
      bushcricket Ephippiger ephippiger shows unusual patterns of intraspecific
      variation in multiple traits across Southern Europe. This is centred in Southern
      France, and evidence implies that it results from secondary contact after
      differentiation in Pleistocene refugia. However, the possible time scales
      involved, locations of the refugia and patterns of expansion remain obscure. This
      study sequenced the COII (507 BP) and cyt b (428 BP) mitochondrial genes to
      examine the intraspecific phylogeography of Western European samples of E.
      ephippiger. A minimum evolution tree revealed little resolution between described
      subspecies of E. ephippiger. Strikingly, populations from the Pyrenees and
      Mediterranean coastal region contained a complex genetic structure corresponding
      to major river valleys, independent of the traditional taxonomy. Samples of the
      subspecies E. e. vitium formed a distinct clade, perhaps supporting their
      taxonomic status. However, other forms (cruciger and cunii) were not genetically
      distinct, which is surprising given differences in their morphology and
      behaviour. The extent of the genetic divergence between Pyreneen valleys is
      unexpectedly deep, with average Tamura-Nei distances of around 14% (net distances
      of 11%) separating the main clades of coding COII sequences. Cyt b showed a
      similar pattern, but was confounded by some non-coding probable pseudogenes. If a
      conventional insect molecular clock is applied, these cryptic clades must pre
      date the Pleistocene, and hypotheses for their history are discussed. However,
      mtDNA divergence in Ephippiger is not evolving in a clock-like manner, because a
      likelihood ratio test rejects clock assumptions for the COII sequences.

PMID- 16955114
TI  - Genetic structure of Africanized honeybee populations (Apis mellifera L.) from
      Brazil and Uruguay viewed through mitochondrial DNA COI-COII patterns.
AB  - Mitochondrial genotypes of Africanized honeybees from Brazil and Uruguay were
      surveyed by DraI restriction of the COI-COII region. Eleven mitotypes were found,
      three of which had not previously been described (A28-A30). Out of 775 samples
      (725 from Brazil, 50 from Uruguay), 197 were A1 and 520 were A4. A1 frequency
      increases toward the north of Brazil, whereas A4 frequency increases toward the
      south, a pattern echoing the African distribution. The origin of the A4 and most
      of the A1 African patterns can be attributed to the introduction of Apis
      mellifera scutellata into Brazil in 1956. The A29 and A30 patterns have the P1
      sequence observed in many Iberian Peninsula samples, which represent the traces
      of the introductions into Brazil and Uruguay by settlers.

PMID- 16955115
TI  - Subgroups of patients with cancer with different symptom experiences and quality
      of-life outcomes: a cluster analysis.
AB  - PURPOSE/OBJECTIVES: To identify subgroups of outpatients with cancer based on
      their experiences with the symptoms of fatigue, sleep disturbance, depression,
      and pain; to explore whether patients in the subgroups differed on selected
      demographic, disease, and treatment characteristics; and to determine whether
      patients in the subgroups differed on two important patient outcomes: functional
      status and quality of life (QOL). DESIGN: Descriptive, correlational study.
      SETTING: Four outpatient oncology practices in northern California. SAMPLE: 191
      outpatients with cancer receiving active treatment. METHODS: Patients completed a
      demographic questionnaire, Karnofsky Performance Status scale, Lee Fatigue Scale,
      General Sleep Disturbance Scale, Center for Epidemiological Studies Depression
      Scale, Multidimensional Quality-of-Life Scale Cancer, and a numeric rating scale
      of worst pain intensity. Medical records were reviewed for disease and treatment
      information. Cluster analysis was used to identify patient subgroups based on
      patients symptom experiences. Differences in demographic, disease, and treatment
      characteristics as well as in outcomes were evaluated using analysis of variance
      and chi square analysis. MAIN RESEARCH VARIABLES: Subgroup membership, fatigue,
      sleep disturbance, depression, pain, functional status, and QOL. FINDINGS: Four
      relatively distinct patient subgroups were identified based on patients
      experiences with four highly prevalent and related symptoms. CONCLUSIONS: The
      subgroup of patients who reported low levels of all four symptoms reported the
      best functional status and QOL. IMPLICATIONS FOR NURSING: The findings from this
      study need to be replicated before definitive clinical practice recommendations
      can be made. Until that time, clinicians need to assess patients for the
      occurrence of multiple symptoms that may place them at increased risk for poorer
      outcomes.

PMID- 16955116
TI  - Lost in translation.

PMID- 16955117
TI  - The bridge from genomic discoveries to disease prevention. 2006 Oncology Nursing
      Society Clinical Lectureship.

PMID- 16955118
TI  - Life after cancer: what does sexuality have to do with it? 2006 Mara Mogensen
      Flaherty Memorial Lectureship.

PMID- 16955119
TI  - Immune globulin IV therapy: optimizing care of patients in the oncology setting.
AB  - PURPOSE/OBJECTIVES: To review major clinical applications of immune globulin IV
      (IGIV) therapy, properties of currently available IGIV preparations, procedures
      for dosing and administration, management of infusion-related adverse effects,
      and strategies for effective patient education. DATA SOURCES: Published articles,
      abstracts, and textbook chapters. DATA SYNTHESIS: IGIV therapy supports immune
      function by providing immunoglobulin G antibodies for protection against
      pathogens and modulation of autoimmune and other potentially damaging host
      responses. Licensed uses include treatment of primary immune deficiencies and
      autoimmune conditions and prophylaxis against viral infection. CONCLUSIONS: The
      safety and effectiveness of IGIV therapy depend on selection of an appropriate
      product, dosage, and infusion rate; patient comorbidities and other risk factors;
      and patient education and treatment adherence. IMPLICATIONS FOR NURSING: Nurses
      have an essential role in the safe and effective use of IGIV, from educating
      patients about the rationale for and effects of therapy to administering the
      product and monitoring for adverse effects.

PMID- 16955120
TI  - Understanding the moral distress of nurses witnessing medically futile care.
AB  - PURPOSE/OBJECTIVES: To explore the topic of moral distress in nurses related to
      witnessing futile care. DATA SOURCES: Literature related to moral distress and
      futility; analysis of narratives written by 108 nurses attending one of two
      national continuing education courses on end-of-life care regarding their
      experiences in the area. DATA SYNTHESIS: Nurses were invited to share a clinical
      situation in which they experienced moral distress related to a patient receiving
      care that they considered futile. Nurses described clinical situations across
      care settings, with the most common conflict being that aggressive care denies
      palliative care. Conflicts regarding code status, life support, and nutrition
      also were common. Patients with cancer were involved quite often, second only to
      geriatric patients and patients with dementia. The instances created strong
      emotional responses from nurses, including feeling the need for patient advocacy
      and that futile care was violent and cruel. Important spiritual and religious
      factors were cited as influencing the clinical experiences. CONCLUSIONS:
      Instances of futile care evoke strong emotional responses from nurses, and nurses
      require support in dealing with their distress. IMPLICATIONS FOR NURSING: The
      ethical dilemma of futile care is complex. Additional research and support are
      needed for patients, families, and nurses.

PMID- 16955121
TI  - Symptom clusters and quality of life in survivors of lung cancer.
AB  - PURPOSE/OBJECTIVES: To explore the prevalence and intensity of depression,
      fatigue, and pain in survivors of lung cancer; to examine the relationship of
      symptoms in a cluster; and to examine the relationship of the symptom cluster to
      quality of life (QOL). DESIGN: Secondary data analysis. SETTING: Online lung
      cancer support group. SAMPLE: 51 patients diagnosed with lung cancer. METHODS:
      Mailed survey with self-report of depression, fatigue, and pain measured by
      subscales of the Short-Form 36 Health Status Survey and QOL measured by the Fox
      Simple QOL Scale. Pearson's correlation and multiple regression analyses were
      used to examine the possible symptom cluster. MAIN RESEARCH VARIABLES:
      Depression, fatigue, pain, and QOL. FINDINGS: Depression, fatigue, and pain were
      found in a majority of survivors, with pain being the least common symptom.
      Fatigue was the most intense of the three symptoms. Two significantly correlated
      symptoms were depression and fatigue. The cluster explained 29% (p less than
      0.01) of the variance in QOL in the lung cancer survivors. CONCLUSIONS: The data
      provided preliminary support for the presence of a symptom cluster in patients
      with lung cancer consisting of depression and fatigue. The cluster had a negative
      relationship with QOL. Survivors of lung cancer have depression and fatigue that
      affect QOL. IMPLICATIONS FOR NURSING: Healthcare providers must assess the
      potential for symptoms to cluster, adversely affecting key patient outcomes such
      as QOL. Through increased knowledge of symptom clusters, clinicians will be able
      to more effectively target the most distressing set of symptoms for intervention.

PMID- 16955122
TI  - The effects of exercise on body weight and composition in breast cancer
      survivors: an integrative systematic review.
AB  - PURPOSE/OBJECTIVES: To examine the research literature regarding the effects of
      exercise on body weight and composition in breast cancer survivors. DATA SOURCES:
      Primary studies in English published from 1989-2004, located through electronic
      databases, hand searches, and personal contacts. DATA SYNTHESIS: Of 1,314 studies
      screened, 14 met all inclusion criteria. Body weight and composition generally
      were secondary endpoints. Effects on weight were less common than reduction in
      percentage of body fat. CONCLUSIONS: The evidence regarding exercise as a
      strategy for body weight and composition management in breast cancer is sparse.
      Research that considers these outcomes as primary endpoints is needed. Numerous
      measurement issues need to be addressed in future studies. IMPLICATIONS FOR
      NURSING: Exercise may help to control adverse body weight and composition changes
      among breast cancer survivors. Improved research that assigns these outcomes
      primary importance will greatly enhance clinicians' ability to assist women in
      body weight and composition management.

PMID- 16955123
TI  - Recruiting participants to cancer prevention clinical trials: lessons from
      successful community oncology networks.
AB  - PURPOSE/OBJECTIVES: To describe the organizational designs and task environments
      of community oncology networks with high accrual rates to cancer prevention
      clinical trials. DESIGN: Replicated case study design; structural contingency
      theory. SETTING: Local Community Clinical Oncology Programs (CCOPs) funded by the
      National Cancer Institute to test preventive and therapeutic interventions in
      community settings. SAMPLE: Primary sample: oncology professionals affiliated
      with four CCOPs ranking among the top 10 in earned cancer control accrual credits
      in fiscal years 1999-2003. Secondary sample: oncology professionals affiliated
      with three CCOPs ranking among the top 10 three to four times during the study
      period. A total of 63 people participated in the interviews. METHODS: Primary
      sample: on-site interviews with CCOP investigators, clinical research staff, and
      nononcology physicians. Secondary sample: telephone interviews with each CCOP's
      nurse administrator and at least one prevention research nurse. MAIN RESEARCH
      VARIABLES: Staffing patterns, organizational processes, recruitment strategies,
      and environmental characteristics. FINDINGS: All of the CCOPs employed dedicated
      prevention research staff. Recruitment through media publicity, mass mailings, or
      group information sessions worked best when prevention trials had flexible
      eligibility requirements and evaluated interventions with few health risks.
      Prevention trials evaluating agents with known toxicities in high-risk
      populations required more targeted recruitment through cancer screening programs,
      physician referral networks, and one-on-one discussions with protocol candidates.
      CONCLUSIONS: High-performing CCOPs configured their structures, processes, and
      recruitment strategies to fit with accrual goals. They also benefited from stable
      and supportive task environments. IMPLICATIONS FOR NURSING: Nurse-coordinated
      research networks have great potential to generate new knowledge about cancer
      prevention that can reduce cancer incidence and mortality significantly.

PMID- 16955124
TI  - Claiming health: mammography screening decision making of African American women.
AB  - PURPOSE/OBJECTIVES: To develop a substantive theory that explains how African
      American women aged 50 years and older of different socioeconomic status (SES)
      make decisions about mammography screening. DESIGN: Qualitative, grounded theory.
      SETTING: Churches, places of employment, or women's homes in a large city in
      Ohio. SAMPLE: 30 women aged 52-72 years; 16 in the initial sample and 14 in the
      theoretical sample. METHODS: Audiotaped interviews and extensive written field
      notes; interviews were transcribed verbatim and analyzed using the constant
      comparison method, resulting in saturation of data. MAIN RESEARCH VARIABLES:
      Decision-making processes explaining mammography screening. FINDINGS: "Claiming
      health" emerged as the substantive theory explaining decisions that affect
      mammography screening and was embedded in the social contexts of cultural
      heritage and learned kinship values, religious beliefs and supports, and prior
      negative experiences with healthcare professionals and the healthcare system.
      Claiming health involved sisterhood and fellowship relationships fostered in the
      church. Claiming health was differentiated by age and SES, with older women of
      lower SES reporting greater reliance on cultural heritage and negative
      recollections of the healthcare system when making decisions regarding
      mammography. Each subconcept of claiming health was equally important and
      influenced decision making. CONCLUSIONS: Oncology nurses can benefit from the
      information presented by assisting older women of lower SES who may have
      encountered negative experiences in the healthcare system to develop effective
      assertiveness and communication skills when interacting with healthcare
      professionals. IMPLICATIONS FOR NURSING: Further research is needed to determine
      whether claiming health is a way of thinking about health generally or is used
      solely to explain experiences with mammography screening.

PMID- 16955125
TI  - Evaluation of the decision support computer program for cancer pain management.
AB  - PURPOSE/OBJECTIVES: To evaluate a decision support computer program (DSCP) for
      cancer pain management. DESIGN: An Internet intervention study to evaluate the
      usage profile, accuracy, and acceptance of the DSCP. SETTING: Internet and
      community settings. SAMPLE: 122 nurses working with patients with cancer were
      recruited through the Internet through a convenience sampling method. METHODS:
      The instruments included tools for registration and for evaluation of the DSCP.
      To evaluate the DSCP, the usage profile was measured by counting the total number
      of cases in which the participants used the DSCP; accuracy was measured by
      determining whether the decision support from the DSCP was appropriate and
      accurate; and acceptance was measured using the Questionnaire for User
      Interaction Satisfaction. MAIN RESEARCH VARIABLES: Usage profile, accuracy, and
      acceptance of the DSCP. FINDINGS: Participants used the DSCP an average of 1.49
      times per person (SD = 1.16). Eighty-eight percent of the participants evaluated
      the DSCP as appropriate and accurate. The mean scores of overall satisfaction in
      four major areas of the computer program ranged from 7.46-9.69. CONCLUSIONS: The
      DSCP could provide accurate and acceptable computerized evidence-based practice
      guidelines for cancer pain management. IMPLICATIONS FOR NURSING: The findings
      suggest that researchers should develop decision support systems in multiple
      aspects and dimensions of cancer pain experience and that hand-held devices would
      increase the usability of the DSCP.

PMID- 16955126
TI  - Developing a family-level intervention for families of children with cancer.
AB  - PURPOSE/OBJECTIVES: To determine the feasibility and effectiveness of a family
      level intervention for parents of children newly diagnosed with cancer. DESIGN: A
      one-group, pretest and post-test, quasi-experimental design. SETTING: A
      university hospital in Iceland. SAMPLE: 10 families (19 parents) of children and
      adolescents newly diagnosed with cancer. METHODS: Parents were asked to answer
      questionnaires at baseline and then twice after the intervention, at 6 and 12
      months. MAIN RESEARCH VARIABLES: Acceptability and short-term effects on parents'
      well-being, coping behavior, hardiness, and adaptation of an educational and
      informational home page, support offered on the Internet to parents, and one or
      two 60- to 90-minute support interviews. FINDINGS: Most of the families indicated
      that the intervention was important, helpful, and supportive, but the level of
      usefulness of the intervention varied. Information from the hypotheses testing,
      that parents' level of well-being increased significantly one month after the
      intervention and that fathers found it helpful to maintain social support and
      psychological stability after the intervention, are optimistic indicators and
      support a possible short-term effect of the intervention. CONCLUSIONS: Offering a
      family-level educational and support intervention was feasible and may be
      effective for such families. IMPLICATIONS FOR NURSING: Researchers and clinicians
      may want to enhance the intervention and test it on bigger samples and with a
      control group.

PMID- 16955127
TI  - Completing a life: comfort level and ease of use of a CD-ROM among seriously ill
      patients.
AB  - PURPOSE/OBJECTIVES: To evaluate use of a CD-ROM titled Completing a Life among
      patients diagnosed with serious illnesses for comfort level with content and ease
      of computer use. DESIGN: A prospective pilot study collected a convenience sample
      of 50 people diagnosed with life-limiting illnesses during a six-month period.
      SETTING: The hematology/oncology department of a large healthcare system located
      in a metropolitan area in the midwestern United States. SAMPLE: Convenience
      sample of 50 patients diagnosed with life-limiting illnesses. Of the patients
      enrolled (age range = 38-93 years), 72% were female, 68% were Caucasian, 50% were
      diagnosed with breast cancer or nonsolid tumors, and 40% were newly diagnosed.
      METHODS: Subjects viewed the CD-ROM and completed pre- and post-intervention
      surveys. MAIN RESEARCH VARIABLES: Comfort level with educational media, comfort
      level of information viewed, and areas of CD-ROM viewed compared to age and stage
      of illness. FINDINGS: Ninety percent of patients reported that they were somewhat
      or very comfortable with the CD-ROM as a learning tool, and ease of use was rated
      at 98%. Patients' comfort level with the material increased from 76% to 90% after
      they viewed the CD-ROM. CONCLUSIONS: The pilot study suggests that the Completing
      a Life CD-ROM can be used with patients facing serious or life-limiting illnesses
      as an additional resource tool for information. IMPLICATIONS FOR NURSING: Nurses
      typically provide the bulk of educational material for their patients. With
      limited resources available regarding management of life-limiting illnesses, this
      resource may provide an excellent addition to resources currently available.

PMID- 16955128
TI  - Level of fatigue in women receiving dose-dense versus standard chemotherapy for
      breast cancer: a pilot study.
AB  - PURPOSE/OBJECTIVES: To determine whether women receiving dose-dense chemotherapy
      for breast cancer experience different levels of fatigue than women receiving
      standard chemotherapy regimens for the disease. DESIGN: Quasi-experimental pilot
      study. SETTING: Private physicians' offices in California. SAMPLE: 15 women with
      stage I, II, or III breast cancer receiving dose-dense or standard chemotherapy.
      The average female participant was 48 years old (mean = 48.3), was married (80%),
      and had a college degree (73%). METHODS: The revised Piper Fatigue Scale was
      completed by patients at three different times: pretreatment, three days after
      their cycle 1 chemotherapy dose, and three days after their cycle 2 chemotherapy
      dose. Patients returned completed surveys by mail. MAIN RESEARCH VARIABLES:
      Fatigue levels associated with chemotherapy. FINDINGS: Pretreatment total fatigue
      scores were not significantly different in the dose-dense and standard
      chemotherapy groups. Total fatigue scores were significantly higher in the dose
      dense group at the cycle 1 and 2 time points. Fatigue scores were significantly
      higher in women who had undergone a mastectomy, were working, were HER2 positive,
      and had a tumor size larger than 2 cm. CONCLUSIONS: Dose-dense chemotherapy
      resulted in significantly greater fatigue. IMPLICATIONS FOR NURSING: Nurses
      should educate women receiving dose-dense chemotherapy as part of informed
      consent and assist them in preparing and planning for fatigue. Information about
      which patients are more likely to experience significant fatigue allows nurses to
      judge the frequency with which they need to assess and manage fatigue to improve
      patient outcomes.

PMID- 16955129
TI  - Supporting junior faculty in the academic system: time for a change?
AB  - Recently, MIT professor and Nobel laureate Susumu Tonegawa has come under attack
      for allegedly opposing the recruitment of a female, prospective junior faculty
      member to MIT because her work would compete with that of his laboratory. While
      the accusations are still under internal investigation, this incident raises the
      important issue of how we scientists as a group succeed or fail as mentors for
      junior faculty.

PMID- 16955130
TI  - A mighty mouse: building a better model of multiple sclerosis.
AB  - The 2 cardinal cell populations mediating adaptive immunity are T and B
      lymphocytes. These cells play important but poorly understood roles in the
      immunopathological demyelinating disease multiple sclerosis (MS) and in a widely
      used animal model of human MS known as EAE. In the current issue of the JCI, 2
      research teams report their parallel studies of double-transgenic mice expressing
      T and B cell receptors that recognize the same myelin protein (see the related
      articles beginning on pages 2385 and 2393). More than half of the double
      transgenic mice spontaneously developed autoimmune demyelination in their spinal
      cords and optic nerves, exhibiting pathologies reminiscent of human MS. The
      studies describe an important new model for MS research.

PMID- 16955131
TI  - Regeneration of the endothelium as a novel therapeutic strategy for acute lung
      injury.
AB  - Acute lung injury (ALI) is characterized by the influx of protein-rich edematous
      fluid into the airspaces due to increased permeability of the alveolar-capillary
      barrier. Inflammatory mediators are thought to play a critical role in the
      pathogenesis of this disorder. In this issue of the JCI, Zhao et al. report that
      the forkhead box M1 (FoxM1) transcription factor induces endothelial regeneration
      and thereby restores endothelial barrier function after ALI (see the related
      article beginning on page 2333). Their findings raise the intriguing possibility
      that the promotion of endothelial regeneration may be a novel therapeutic
      strategy for ALI.

PMID- 16955132
TI  - Toll-like receptors and IFN-alpha: partners in autoimmunity.
AB  - Many autoimmune diseases are thought to be precipitated by viral infections. In
      this issue of the JCI, Lang et al. demonstrate that, in a mouse model of
      autoimmune hepatitis, viral infections not only trigger expansion of self
      reactive T cells but also activate antigen-presenting cells through TLR
      stimulation (see the related article beginning on page 2456). Activated cells
      then secrete IFN-alpha and TNF-alpha, which trigger tissue release of chemokines
      that attract self-reactive CD8+ T cells, ultimately leading to liver damage.

PMID- 16955133
TI  - Cholesterol precursors and facial clefting.
AB  - Inborn errors of cholesterol synthesis cause human malformation syndromes,
      including Smith-Lemli-Opitz syndrome, lathosterolosis, desmosterolosis, X-linked
      dominant chondrodysplasia punctata type 2, and congenital hemidysplasia with
      ichthyosiform erythroderma and limb defects. Because adequate cholesterol is not
      transported across the placenta, low cholesterol and elevated sterol precursor
      levels are present during embryogenesis. It has been debated whether the
      malformations result from low cholesterol or the buildup of sterol precursors. In
      this issue of the JCI, Engelking et al. provide evidence that sterol precursor
      accumulation plays a pivotal role in the genesis of facial malformations (see the
      related article beginning on page 2356).

PMID- 16955134
TI  - Adaptive human regulatory T cells: myth or reality?
AB  - It is now well established that a distinct subset of T lymphocytes is essential
      for downregulating immune responses to both endogenous (self) and exogenous
      antigens. These Tregs are CD4+ and express high levels of CD25 (the alpha chain
      of the IL-2 receptor) and the transcription factor Foxp3. The mechanisms
      determining the lifespan, homeostasis, and in vivo generation of these Tregs are
      still ill defined. A study by Vukmanovic-Stejic et al. in this issue of the JCI
      shows that in humans, Tregs are present throughout life but that despite their
      high throughput, they are short lived (see the related article beginning on page
      2423). It is thus unlikely that all CD4+ CD25hi Foxp3+ Tregs are generated as a
      separate lineage in the thymus. The authors propose that during adulthood, Tregs
      essentially emerge at the periphery from the memory T cell pool.

PMID- 16955135
TI  - You say estren, I say estrogen. Let's call the whole replacement off!
AB  - Estrogens and androgens play a key role in regulating bone mass. However, their
      clinical use as bone anabolic agents is limited due to unwanted side effects,
      particularly in reproductive organs. In 2002, the synthetic ligand estren was
      described to reproduce the bone anabolic, nongenotropic effects of sex steroids
      while having no effect on the uterus or seminal vesicles. But in the current
      issue of the JCI, Windahl et al. provide data showing that estrens are not as
      suitable a replacement for estrogen as was initially reported (see the related
      article beginning on page 2500). Though not catabolic, estrens triggered only
      minor, nonsignificant increases in bone mass in gonadectomized mice, all the
      while inducing hypertrophy of reproductive organs. Does this mean estrens should
      not be pursued as a therapy for osteoporosis?

PMID- 16955136
TI  - Deconstructing endothelial dysfunction: soluble guanylyl cyclase oxidation and
      the NO resistance syndrome.
AB  - In this issue of the JCI, Stasch and colleagues suggest that a novel drug, BAY 58
      2667, potently activates a pool of oxidized and heme-free soluble guanylyl
      cyclase (sGC; see the related article beginning on page 2552). The increased
      vasodilatory potency of BAY 58-2667 the authors found in a number of animal
      models of endothelial dysfunction and in human blood vessels from patients with
      diabetes suggests that there exists a subphenotype of endothelial dysfunction
      characterized by receptor-level NO resistance. Diseases associated with NO
      resistance would appear to be ideally suited for therapies directed at restoring
      redox homeostasis, sGC activity, and NO sensitivity.

PMID- 16955137
TI  - Endothelial cell-restricted disruption of FoxM1 impairs endothelial repair
      following LPS-induced vascular injury.
AB  - Recovery of endothelial integrity after vascular injury is vital for endothelial
      barrier function and vascular homeostasis. However, little is known about the
      molecular mechanisms of endothelial barrier repair following injury. To
      investigate the functional role of forkhead box M1 (FoxM1) in the mechanism of
      endothelial repair, we generated endothelial cell-restricted FoxM1-deficient mice
      (FoxM1 CKO mice). These mutant mice were viable and exhibited no overt phenotype.
      However, in response to the inflammatory mediator LPS, FoxM1 CKO mice displayed
      significantly protracted increase in lung vascular permeability and markedly
      increased mortality. Following LPS-induced vascular injury, FoxM1 CKO lungs
      demonstrated impaired cell proliferation in association with sustained expression
      of p27(Kip1) and decreased expression of cyclin B1 and Cdc25C. Endothelial cells
      isolated from FoxM1 CKO lungs failed to proliferate, and siRNA-mediated
      suppression of FoxM1 expression in human endothelial cells resulted in defective
      cell cycle progression. Deletion of FoxM1 in endothelial cells induced decreased
      expression of cyclins, Cdc2, and Cdc25C, increased p27(Kip1) expression, and
      decreased Cdk activities. Thus, FoxM1 plays a critical role in the mechanism of
      the restoration of endothelial barrier function following vascular injury. These
      data suggest that impairment in FoxM1 activation may be an important determinant
      of the persistent vascular barrier leakiness and edema formation associated with
      inflammatory diseases.

PMID- 16955138
TI  - Severe facial clefting in Insig-deficient mouse embryos caused by sterol
      accumulation and reversed by lovastatin.
AB  - Insig-1 and Insig-2 are regulatory proteins that restrict the cholesterol
      biosynthetic pathway by preventing proteolytic activation of SREBPs and by
      enhancing degradation of HMG-CoA reductase. Here, we created Insig-double
      knockout (Insig-DKO) mice that are homozygous for null mutations in Insig-1 and
      Insig-2. After 18.5 days of development, 96% of Insig-DKO embryos had defects in
      midline facial development, ranging from cleft palate (52%) to complete cleft
      face (44%). Middle and inner ear structures were abnormal, but teeth and
      skeletons were normal. The animals were lethargic and runted; they died within 1
      day of birth. The livers and heads of Insig-DKO embryos overproduced sterols,
      causing a marked buildup of sterol intermediates. Treatment of pregnant mice with
      the HMG-CoA reductase inhibitor lovastatin reduced sterol synthesis in Insig-DKO
      embryos and reduced the pre-cholesterol intermediates. This treatment ameliorated
      the clefting syndrome so that 54% of Insig-DKO mice had normal faces, and only 7%
      had cleft faces. We conclude that buildup of pre-cholesterol sterol intermediates
      interferes with midline fusion of facial structures in mice. These findings have
      implications for the pathogenesis of the cleft palate component of Smith-Lemli
      Opitz syndrome and other human malformation syndromes in which mutations in
      enzymes catalyzing steps in cholesterol biosynthesis produce a buildup of sterol
      intermediates.

PMID- 16955139
TI  - CD40 induces macrophage anti-Toxoplasma gondii activity by triggering autophagy
      dependent fusion of pathogen-containing vacuoles and lysosomes.
AB  - Many intracellular pathogens, including Toxoplasma gondii, survive within
      macrophages by residing in vacuoles that avoid fusion with lysosomes. It is
      important to determine whether cell-mediated immunity can trigger macrophage
      antimicrobial activity by rerouting these vacuoles to lysosomes. We report that
      CD40 stimulation of human and mouse macrophages infected with T. gondii resulted
      in fusion of parasitophorous vacuoles and late endosomes/lysosomes.
      Vacuole/lysosome fusion took place even when CD40 was ligated after the formation
      of parasitophorous vacuoles. Genetic and pharmacological approaches that impaired
      phosphoinositide-3-class 3 (PIK3C3), Rab7, vacuolar ATPase, and lysosomal enzymes
      revealed that vacuole/lysosome fusion mediated antimicrobial activity induced by
      CD40. Ligation of CD40 caused colocalization of parasitophorous vacuoles and LC3,
      a marker of autophagy, which is a process that controls lysosomal degradation.
      Vacuole/lysosome fusion and antimicrobial activity were shown to be dependent on
      autophagy. Thus, cell-mediated immunity through CD40 stimulation can reroute an
      intracellular pathogen to the lysosomal compartment, resulting in macrophage
      antimicrobial activity.

PMID- 16955140
TI  - Spontaneous opticospinal encephalomyelitis in a double-transgenic mouse model of
      autoimmune T cell/B cell cooperation.
AB  - We describe a double-transgenic mouse strain (opticospinal EAE [OSE] mouse) that
      spontaneously develops an EAE-like neurological syndrome closely resembling a
      human variant of multiple sclerosis, Devic disease (also called neuromyelitis
      optica). Like in Devic disease, the inflammatory, demyelinating lesions were
      located in the optic nerve and spinal cord, sparing brain and cerebellum, and the
      murine lesions showed histological similarity with their human correlates. OSE
      mice have recombination-competent immune cells expressing a TCR-alphabeta
      specific for myelin oligodendrocyte glycoprotein (MOG) aa 35-55 peptide in the
      context of I-Ab along with an Ig J region replaced by the recombined heavy chain
      of a monoclonal antibody binding to a conformational epitope on MOG. OSE mouse B
      cells bound even high dilutions of recombinant MOG, but not MOG peptide, and
      processed and presented it to autologous T cells. In addition, in OSE mice, but
      not in single-transgenic parental mice, anti-MOG antibodies were switched from
      IgM to IgG1.

PMID- 16955141
TI  - Myelin oligodendrocyte glycoprotein-specific T and B cells cooperate to induce a
      Devic-like disease in mice.
AB  - Multiple sclerosis (MS) is a clinically and pathologically heterogeneous
      inflammatory/demyelinating disease of the CNS. In the MS variant Devic disease,
      lesions are predominantly found in the optic nerves and spinal cord but not the
      brain. The immunological bases of the different forms of MS are unknown. We
      previously generated myelin oligodendrocyte glycoprotein-specific (MOG-specific)
      TCR transgenic mice (TCRMOG mice; also referred to as 2D2 mice) and reported that
      a large proportion of these mice develop spontaneous isolated optic neuritis. We
      have now crossed the TCRMOG mice with MOG-specific Ig heavy-chain knock-in mice
      (IgHMOG mice; also referred to as Th mice), in which one-third of the B cells are
      specific for MOG. In these mice, MOG-specific B cells are very efficient in
      presenting MOG to the transgenic T cells and undergo class switching to IgG1 in
      the presence of the transgenic T cells. Sixty percent of TCRMOG x IgHMOG mice
      spontaneously developed a severe form of experimental autoimmune
      encephalomyelitis (EAE). Histological examination of the CNS revealed a selective
      distribution of meningeal and parenchymal inflammatory lesions in the spinal cord
      and optic nerves. Thus, CNS antigen-specific T and B cells cooperate to induce a
      distinct clinicopathologic EAE pattern that closely replicates human Devic
      disease.

PMID- 16955142
TI  - Human CD4+ CD25hi Foxp3+ regulatory T cells are derived by rapid turnover of
      memory populations in vivo.
AB  - While memory T cells are maintained by continuous turnover, it is not clear how
      human regulatory CD4+ CD45RO+ CD25hi Foxp3+ T lymphocyte populations persist
      throughout life. We therefore used deuterium labeling of cycling cells in vivo to
      determine whether these cells could be replenished by proliferation. We found
      that CD4+ CD45RO+ Foxp3+ CD25hi T lymphocytes were highly proliferative, with a
      doubling time of 8 days, compared with memory CD4+ CD45RO+ Foxp3- CD25- (24 days)
      or naive CD4+ CD45RA+ Foxp3- CD25- populations (199 days). However, the
      regulatory population was susceptible to apoptosis and had critically short
      telomeres and low telomerase activity. It was therefore unlikely to be self
      regenerating. These data are consistent with continuous production from another
      population source. We found extremely close TCR clonal homology between
      regulatory and memory CD4+ T cells. Furthermore, antigen-related expansions
      within certain TCR Vbeta families were associated with parallel numerical
      increases of CD4+ CD45RO+ CD25hi Foxp3+ Tregs with the same Vbeta usage. It is
      therefore unlikely that all human CD4+ CD25+ Foxp3+ Tregs are generated as a
      separate functional lineage in the thymus. Instead, our data suggest that a
      proportion of this regulatory population is generated from rapidly dividing,
      highly differentiated memory CD4+ T cells; this has considerable implications for
      the therapeutic manipulation of these cells in vivo.

PMID- 16955143
TI  - Immunoprivileged status of the liver is controlled by Toll-like receptor 3
      signaling.
AB  - The liver is known to be a classical immunoprivileged site with a relatively high
      resistance against immune responses. Here we demonstrate that highly activated
      liver-specific effector CD8+ T cells alone were not sufficient to trigger immune
      destruction of the liver in mice. Only additional innate immune signals
      orchestrated by TLR3 provoked liver damage. While TLR3 activation did not
      directly alter liver-specific CD8+ T cell function, it induced IFN-alpha and TNF
      alpha release. These cytokines generated expression of the chemokine CXCL9 in the
      liver, thereby enhancing CD8+ T cell infiltration and liver disease in mice.
      Thus, nonspecific activation of innate immunity can drastically enhance
      susceptibility to immune destruction of a solid organ.

PMID- 16955144
TI  - TRAIL receptor-mediated JNK activation and Bim phosphorylation critically
      regulate Fas-mediated liver damage and lethality.
AB  - TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family with
      potent apoptosis-inducing properties in tumor cells. In particular, TRAIL
      strongly synergizes with conventional chemotherapeutic drugs to induce tumor cell
      death. Thus, TRAIL has been proposed as a promising future cancer therapy.
      Little, however, is known regarding what the role of TRAIL is in normal
      untransformed cells and whether therapeutic administration of TRAIL, alone or in
      combination with other apoptotic triggers, may cause tissue damage. In this
      study, we investigated the role of TRAIL in Fas-induced (CD95/Apo-1-induced)
      hepatocyte apoptosis and liver damage. While TRAIL alone failed to induce
      apoptosis in isolated murine hepatocytes, it strongly amplified Fas-induced cell
      death. Importantly, endogenous TRAIL was found to critically regulate anti-Fas
      antibody-induced hepatocyte apoptosis, liver damage, and associated lethality in
      vivo. TRAIL enhanced anti-Fas-induced hepatocyte apoptosis through the activation
      of JNK and its downstream substrate, the proapoptotic Bcl-2 homolog Bim.
      Consistently, TRAIL- and Bim-deficient mice and wild-type mice treated with a JNK
      inhibitor were protected against anti-Fas-induced liver damage. We conclude that
      TRAIL and Bim are important response modifiers of hepatocyte apoptosis and
      identify liver damage and lethality as a possible risk of TRAIL-based tumor
      therapy.

PMID- 16955145
TI  - Bone protection by estrens occurs through non-tissue-selective activation of the
      androgen receptor.
AB  - The use of estrogens and androgens to prevent bone loss is limited by their
      unwanted side effects, especially in reproductive organs and breast. Selective
      estrogen receptor modulators (SERMs) partially avoid such unwanted effects, but
      their efficacy on bone is only moderate compared with that of estradiol or
      androgens. Estrens have been suggested to not only prevent bone loss but also
      exert anabolic effects on bone while avoiding unwanted effects on reproductive
      organs. In this study, we compared the effects of a SERM (PSK3471) and 2 estrens
      (estren-alpha and estren-beta) on bone and reproductive organs to determine
      whether estrens are safe and act via the estrogen receptors and/or the androgen
      receptor (AR). Estrens and PSK3471 prevented gonadectomy-induced bone loss in
      male and female mice, but none showed true anabolic effects. Unlike SERMs, the
      estrens induced reproductive organ hypertrophy in both male and female mice and
      enhanced MCF-7 cell proliferation in vitro. Estrens directly activated
      transcription in several cell lines, albeit at much higher concentrations than
      estradiol or the SERM, and acted for the most part through the AR. We conclude
      that the estrens act mostly through the AR and, in mice, do not fulfill the
      preclinical efficacy or safety criteria required for the treatment or prevention
      of osteoporosis.

PMID- 16955147
TI  - Who would I consider for capsule endoscopy?--Part I.

PMID- 16955146
TI  - Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of
      diseased blood vessels.
AB  - ROS are a risk factor of several cardiovascular disorders and interfere with
      NO/soluble guanylyl cyclase/cyclic GMP (NO/sGC/cGMP) signaling through scavenging
      of NO and formation of the strong oxidant peroxynitrite. Increased oxidative
      stress affects the heme-containing NO receptor sGC by both decreasing its
      expression levels and impairing NO-induced activation, making vasodilator therapy
      with NO donors less effective. Here we show in vivo that oxidative stress and
      related vascular disease states, including human diabetes mellitus, led to an sGC
      that was indistinguishable from the in vitro oxidized/heme-free enzyme. This sGC
      variant represents what we believe to be a novel cGMP signaling entity that is
      unresponsive to NO and prone to degradation. Whereas high-affinity ligands for
      the unoccupied heme pocket of sGC such as zinc-protoporphyrin IX and the novel NO
      independent sGC activator 4-[((4-carboxybutyl){2-[(4
      phenethylbenzyl)oxy]phenethyl}amino) methyl [benzoic]acid (BAY 58-2667)
      stabilized the enzyme, only the latter activated the NO-insensitive sGC variant.
      Importantly, in isolated cells, in blood vessels, and in vivo, BAY 58-2667 was
      more effective and potentiated under pathophysiological and oxidative stress
      conditions. This therapeutic principle preferentially dilates diseased versus
      normal blood vessels and may have far-reaching implications for the currently
      investigated clinical use of BAY 58-2667 as a unique diagnostic tool and highly
      innovative vascular therapy.

PMID- 16955148
TI  - Serum creatinine in patients with advanced liver disease is of limited value for
      identification of moderate renal dysfunction: are the equations for estimating
      renal function better?
AB  - BACKGROUND: The Cockcroft-Gault formula (CGF) is used to estimate the glomerular
      filtration rate (GFR) based on serum creatinine (Cr) levels, age and sex. A new
      formula developed by the Modification of Diet in Renal Disease (MDRD) Study
      Group, based on the patient's Cr levels, age, sex, race and serum urea nitrogen
      and serum albumin levels, has shown to be more accurate. However, the best
      formula to identify patients with advanced liver disease (ALD) and moderate renal
      dysfunction (GFR 60 mL/min/1.73 m2 or less) is not known. The aim of the present
      study was to compare calculations of GFR, using published formulas (excluding
      those requiring urine collections) with standard radionuclide measurement of GFR
      in patients with ALD. METHODS: Fifty-seven consecutive subjects (40% women) with
      a mean age of 50 years (range 16 to 67 years) underwent 99m-technetium
      diethylenetriamine pentaacetic acid (99mTc-DTPA) (single injection) radionuclide
      measurement of GFR. To calculate GFR, three formulas were used: the reciprocal of
      Cr multiplied by 100 (100/Cr), the CGF and the MDRD formulas. Pearson's
      correlation coefficient (r) and Bland-Altman analyses of agreement were used to
      analyze the association between 99mTc-DTPA clearance and the three equations for
      GFR. RESULTS: The mean 99mTc-DTPA clearance was 83 mL/min/1.73 m2 (range 28
      mL/min/1.73 m2 to 173 mL/min/1.73 m2). Mean calculated GFRs by 100/Cr, the CGF
      and the MDRD formula were 106 mL/min/1.73 m2, 98 mL/min/1.73 m2 and 86
      mL/min/1.73 m2, respectively. Regression analysis showed good correlation between
      radionuclide GFR and calculated GFR with r(100/Cr)=0.74, r(CGF)=0.80,
      r(MDRD)=0.87, all at P > or = 0.0001. The MDRD formula provided the least bias.
      The Bland-Altman plot showed best agreement between GFR calculated by the MDRD
      formula and 99mTc-DTPA clearance, with only 3 mL/min/1.73 m2 overestimation.
      There was higher variability between radionuclide GFR and calculated GFR by the
      CGF and by 100/Cr. Although there was no difference in precision, GFR calculated
      by the MDRD formula had the best overall accuracy. The sensitivity and
      specificity for detection of moderate renal dysfunction by the MDRD formulas were
      73% and 87%, respectively. CONCLUSIONS: Among the Cr-based GFR formulas, the MDRD
      formula showed a larger proportion of agreement with radionuclide GFR in patients
      with ALD. In clinical practice, the MDRD is the best formula for detection of
      moderate renal dysfunction among those with ALD.

PMID- 16955149
TI  - Survey of clinical nutrition practices of Canadian gastroenterologists.
AB  - OBJECTIVE: Nutrition education is a required part of gastrointestinal training
      programs. The involvement of gastroenterologists in clinical nutrition once their
      training has been completed is unknown. The aim of the present study was to
      determine the practice pattern of gastroenterologists in clinical nutrition and
      their perceived adequacy of nutrition training during their gastroenterology (GI)
      fellowship. METHODS: The Canadian Association of Gastroenterology mailed a survey
      to all of its 463 Canadian clinician members and 88 trainee members. Components
      of the survey included knowledge of nutritional assessment and total parenteral
      nutrition, involvement in a nutrition support service, physician involvement in
      nutritional assessment and nutrition support teams, obesity management, insertion
      of gastrostomy (G) tubes and management of tube-related complications, and
      adequacy of training in clinical nutrition. RESULTS: Sixty per cent (n=279) of
      the Canadian Association of Gastroenterology clinicians and 38% (n=33) of the
      fellows responded. Of the clinicians, 80% were practicing adult
      gastroenterologists with the following demographics: those practicing full time
      in academic centres (42%), community practice (45%), completed training in the
      last 10 years (32%) and those that completed training in the United States (14%).
      Although only 6% had a primary focus of nutrition in their GI practices, 65% were
      involved in nutrition support (including total parenteral nutrition), 74% placed
      G tubes and 68% managed at least one of the major complications of G tube
      insertion. Respondents felt a gastroenterologist should be the physician's
      consultant on nutrition support services (89%). Areas of potential inadequate
      training included nutritional assessment, indications for nutrition support,
      management of obesity and management of G tube-related complications. The
      majority of clinicians (67%) and trainees (73%) felt that nutrition training in
      their GI fellowship was underemphasized. CONCLUSIONS: The majority of Canadian
      gastroenterologists are involved in nutrition support. However, this survey
      demonstrated that nutritional training is underemphasized in most training
      programs. It is important for GI fellowship programs to develop standardized
      nutrition training that prepares trainees for their practice.

PMID- 16955150
TI  - Acute management and secondary prophylaxis of esophageal variceal bleeding: a
      western Canadian survey.
AB  - BACKGROUND: Acute esophageal variceal bleeding (EVB) is a major cause of
      morbidity and mortality in patients with liver cirrhosis. Guidelines have been
      published in 1997; however, variability in the acute management and prevention of
      EVB rebleeding may occur. METHODS: Gastroenterologists in the provinces of
      British Columbia, Alberta, Manitoba and Saskatchewan were sent a self-reporting
      questionnaire. RESULTS: The response rate was 70.4% (86 of 122). Intravenous
      octreotide was recommended by 93% for EVB patients but the duration was variable.
      The preferred timing for endoscopy in suspected acute EVB was within 12 h in
      75.6% of respondents and within 24 h in 24.6% of respondents. Most (52.3%)
      gastroenterologists do not routinely use antibiotic prophylaxis in acute EVB
      patients. The preferred duration of antibiotic therapy was less than three days
      (35.7%), three to seven days (44.6%), seven to 10 days (10.7%) and throughout
      hospitalization (8.9%). Methods of secondary prophylaxis included repeat
      endoscopic therapy (93%) and beta-blocker therapy (84.9%). Most
      gastroenterologists (80.2%) routinely attempted to titrate beta-blockers to a
      heart rate of 55 beats/min or a 25% reduction from baseline. The most common form
      of secondary prophylaxis was a combination of endoscopic and pharmacological
      therapy (70.9%). CONCLUSIONS: Variability exists in some areas of EVB treatment,
      especially in areas for which evidence was lacking at the time of the last
      guideline publication. Gastroenterologists varied in the use of prophylactic
      antibiotics for acute EVB. More gastroenterologists used combination secondary
      prophylaxis in the form of band ligation eradication and beta-blocker therapy
      rather than either treatment alone. Future guidelines may be needed to address
      these practice differences.

PMID- 16955152
TI  - Acute pancreatitis and upper gastrointestinal bleeding as presenting symptoms of
      duodenal Brunner's gland hamartoma.
AB  - Brunner's gland hamartomas are rare, benign small bowel tumours. There were fewer
      than 150 cases reported in the English literature until the end of the last
      century. These hamartomas may be discovered incidentally during an upper
      gastrointestinal tract endoscopy. Otherwise, they may be diagnosed in patients
      presenting with acute upper gastrointestinal bleeding, anemia or symptoms of
      intestinal obstruction. The case of a young woman admitted for acute upper
      gastrointestinal bleeding along with acute pancreatitis is presented. The
      investigation revealed a giant Brunner's gland hamartoma in the second part of
      the duodenum. After total endoscopic resection of the tumour, the patient has
      remained completely asymptomatic for a follow-up period of seven months.

PMID- 16955153
TI  - [The use of CAD/CAM system with zirconia in modern prosthodontics].
AB  - Computer assisted design/computer assisted machining (CAD/CAM) technology has
      received considerable clinical and research interest from modern dental practices
      as a means of delivering all-ceramic restorations. Up to now the CAD/CAM system
      with zirconia has the highest fracture strength in all all-ceramic materials, and
      consistently enabled the most esthetic, lifelike reproduction of natural
      dentition. They have been widely received by both dentists and patients. The
      CAD/CAM system with zirconia is indicated for crowns and bridges in natural teeth
      or implants and telescope dentures, the CAD/CAM with zirconia can be placed
      anywhere in the mouth, and can replace the porcelain crowns and bridges for
      single crown and bridges less than 6 units. This paper described the techniques
      of CAD/CAM system with zirconia in fabrication of crowns, bridges, telescope
      dentures and implant dentures with colored illustrations.

PMID- 16955151
TI  - A diagnostic approach to hemochromatosis.
AB  - In the present clinical review, a diagnostic approach to hemochromatosis is
      discussed from the perspective of two clinicians with extensive experience in
      this area. The introduction of genetic testing and large-scale population
      screening studies have broadened our understanding of the clinical expression of
      disease and the utility of biochemical iron tests for the detection of disease
      and for the assessment of disease severity. Liver biopsy has become more of a
      prognostic test than a diagnostic test. The authors offer a stepwise, diagnostic
      algorithm based on current evidence-based data, that they regard as most cost
      effective. An early diagnosis can lead to phlebotomy therapy to prevent the
      development of cirrhosis.

PMID- 16955154
TI  - [A preliminary study of nasoalveolar molding for infants born with cleft lip and
      palate].
AB  - PURPOSE: The purpose of this study was to apply nasoalveolar molding appliance in
      infants with cleft lip and plate and to observe the preliminary effects on nasal
      cartilage and columella. METHODS: Ten infants were treated with nasoalveolar
      molding. The other ten infants without any presurgical orthopedic treatment were
      chosen as the control group. Each patient was photographed at the initial visit
      (T0), after nasoalveolar molding (T1), 2 weeks (T2), and half a year (T3) after
      cheiloplasty. Six measurements were made on the photographs and the nasal
      symmetry was analyzed with paired t test. RESULTS: The percentage of the
      deviation from perfect symmetry was significantly improved at T0-T1, T1-T2 stage
      (P<0.05), and the improvement relapsed at T2-T3 (P<0.05). There was significant
      difference between the orthopedic group and the control group with the changes in
      nasal symmetry in vertical dimension (P<0.01), and there was no significant
      difference in horizontal dimension (P>0.05). CONCLUSIONS: Nasal asymmetry was
      significantly improved after nasoalveolar molding. Half a year after the primary
      cheiloplasty, although there was a relapse tendency of nasal asymmetry, the shape
      of the nasal dome was ideal.

PMID- 16955155
TI  - [Influence of smoking on apoptosis in human gingival epithelium].
AB  - PURPOSE: Cigarette smoking was a major risk factor for oral hygiene and
      periodontal status. The study was to investigate the relationship between
      different exposure to cigarette smoke and apoptosis in stratum spinosum and
      stratum basale cells of human gingival epithelium. METHODS: 47 smoking patients
      with crown lengthening surgery or extraction of the impacted teeth were enrolled.
      It comprised 41 males and 6 females. Their age ranged from 18 to 29 years old
      (average age: 21.4). According to smoke history (SH), average cigarettes per day
      (ACD) and total smoke number (TSM), 47 smokers were divided into group I (SH<5a
      or ACD<10 and TSM<15 thousand, n=19), group II (5a< or = SH or 10< or = ACD and
      15 thousand < or =TSM, n=28). Another 10 non-smoking patients were chosen as
      control. Apoptosis was identified by the terminal deoxy-transferase (TdT)
      mediated dUTP-biotin nick end labeling (TUNEL) method. Differences between the
      two groups were analyzed using Student-Newman-Keuls (SNK).The criteria for
      statistical significance was accepted at the probability level P<0.05. RESULTS:
      There was increased apoptosis in stratum spinosumin and stratum basale cells of
      smokers compared to that of non-smokers. Apoptosis in stratum spinosumin cells
      was significantly different between smokers and non-smokers (P<0.01), between
      group I and group II (P<0.01). CONCLUSION: It is conclude that exposure to
      cigarette smoke can increase apoptosis in stratum spinosumin cells of human
      gingival epithelium, which may influence its normal metabolism and protein
      secretion.

PMID- 16955156
TI  - [The effect of the position of artificial premature on mandible moving track
      during opening movement].
AB  - PURPOSE: The purpose of this study was to observe the effect of the position of
      premature on track of mandibular incisal point during opening movement. METHODS:
      The changes of the track of mandibular incisal point along with the change of
      premature position were recorded by Arcus DigMa mandibular moving track analysis
      system. The relativity between the premature position and mandibular incisal
      point moving track on arrowy axis, vertical axis and horizontal axis was
      analyzed. Regression analysis was used for linear correlation between premature
      position and mandible opening moving track. RESULTS: The results showed that
      along with the retrusion of premature, the moving distance of mandibular incisal
      point tended to increase on arrowy axis, while decrease on vertical axis and lean
      to the contralateral side on horizontal axis. The linear regression equation of
      mandibular incisal point moving distance on vertical axis along with the
      premature position was: y=34.7095-0.1590x(1), delta=0.5549, P<0.001. CONCLUSION:
      The position of premature influenced the track of mandibular incisal point during
      opening movement significantly. With the retrusion of premature, the mandible
      opening moving track tended to be more posterior and shifting to the
      contralateral side, and the opening dimension tended to decrease. There was
      linear correlation between premature position and mandible moving track on the
      vertical axis.

PMID- 16955157
TI  - [The effect of chewing gum containing tea polyphenol on salivary flow rate and
      pH].
AB  - PURPOSE: To investigate the change of saliva flow rate and pH after chewing tea
      polyphenol gum. METHODS: Saliva was collected before and after chewing tea
      polyphenol gum and the control gum. Both the salivary flow rate and pH value were
      measured and analyzed by one-way ANOVA and SNK. RESULTS: The chewing gum
      significantly increased the flow rate as well as pH value of the saliva. The flow
      rate of the tested and control gum reached peak in the first minute. They were
      3.15+/-1.05 and 3.30+/-0.87 ml respectively. There was no significant difference
      between the chewing gums. CONCLUSION: Chewing gum can increase the secretion and
      elevate the pH value of the saliva which benefits oral health care.

PMID- 16955158
TI  - [The preliminary study of the treatment timing for rapid maxillary expansion].
AB  - PURPOSE: The aim of this study was to find the treatment timing of rapid
      maxillary expansion by investigating the relationship among the chronologic age,
      dental age, skeletal age and treatment effect of rapid maxillary expansion.
      METHODS: A sample of thirty patients who required rapid maxillary expansion was
      selected. The patients ranged in age from 11 to 14 years, with the mean age being
      12.30 years. Assessment of the skeletal age was made with a hand radiograph
      before treatment. The posteroanterior cephalograms, occlusal radiograph of the
      maxilla were taken at the time of pretreatment and post-treatment. Paired t test
      and multiple regression analysis were used for statistical analysis. RESULTS: The
      results showed that the effects of rapid maxillary expansion were different even
      though the chronologic ages were similar. A negative correlation was found
      between the skeletal age and the expansive effect. Regressive coefficient was 
      6.440, P value was 0.045. There was a significant negative correlation between
      the dental age and the expansive effect. The regressive coefficient was -1.289, P
      value was 0.000. The expansive effect was on the decrease while the second
      maxillary molars erupted continuously. CONCLUSION: It is proposed that rapid
      maxillary expansion could be used successfully before the second maxillary molars
      erupt. The optimal orthopedic effect could be attained.

PMID- 16955159
TI  - [Clinical analysis of PLI, GI and SBI in patients with fixed orthodontic
      appliances].
AB  - PURPOSE: The aim of the present study was to carry out a detailed analysis of the
      data on PLI, GI, SBI in fixed orthodontic patients. METHODS: 375 middle school
      students aged 12 to 15 years old were selected as control group, including 196
      boys and 179 girls. 331 patients with fixed orthodontic appliances aged 12 -15
      years from city were used as experimental group, including 101 boys and 230 girls
      without mouth-breathing. Gingival index (GI), sulcus bleeding index (SBI), and
      plaque index (PLI) were recorded for each individual patient six months after
      being with orthodontic appliances. Four upper and four lower incisors were
      assessed, the data of the two groups were analyzed with SPSS 10.0 software
      package for Student's t test. RESULTS: It was found that there were significant
      higher PLI, GI and SBI values in orthodontic treated patients (P<0.01). Although
      there was no significantly difference in PLI value between boys and girls
      (P>0.05) in the experimental group, there were statistically significant higher
      GI and SBI values compared boys with girls (P<0.01). There were significantly
      higher PLI and GI values in boys' lower incisor(P<0.01). Oral health care was
      difficult in patients with fixed orthodontic appliances. Boys' oral hygiene was
      poorer than girls'. CONCLUSION: In order to maintain periodontal health, it is
      very important to strengthen oral hygiene to children who receive fixed
      appliance, especially in boys, as well as control the level of plaque
      accumulation in the lower incisors.

PMID- 16955160
TI  - [Cephalometric comparisons of the craniofacial characteristics of Class II 1
      malocclusions with different vertical types in adolescences].
AB  - PURPOSE: To compare the craniofacial characteristics in Class II(1) malocclusions
      with different vertical types in adolescence. METHODS: The sample, including 60
      males and 60 females, was divided into three groups equally based on their FMA
      degrees (high-angle group, average-angle group, low-angle group and normal
      occlusion group). Cephalograms were traced for all the subjects. Data were
      obtained to perform analysis of variance and LSD multiple range test. RESULTS: 1.
      The vertical growth of the anterior part of maxilla was greater than the
      posterior part in the three groups with Class II(1) malocclusion. The vertical
      dimension of the composite ramus-cranial floor was deficient relative to that of
      anterior maxilla in the high-angle and average-angle groups, the mandible rotated
      backward, especially in the high-angle group. In the low-angle group, the
      vertical dimension of the composite ramus-cranial floor grew excessively relative
      to that of posterior maxilla. The palatal plane and mandible plane rotated
      forward and upward. 2. The dentoalveolar characteristics of Class II(1)
      malocclusion group showed that: U6 tipped distally, the dentoalveolar height of
      L6 decreased, the functional occlusal plane (FOP) of average-angle group deviated
      away from the neutral occlusal axis (NOA), and rotated downward. In the high-
      angle group, the FOP deviated away from the NOA severely. The vertical
      dentoalveolar heights of U6 were normal. In the low-angle group, the vertical
      dentoalveolar heights of U6, the dentoalveolar height of L6 decreased, the angle
      of FOP between NOA showed no significantly difference from normal-occlusion
      group. CONCLUSION: There were different craniofacial vertical characteristics of
      Class II(1) malocclusion with different vertical types in adolescences. Different
      methods should be used to control the vertical dimensions in different types.

PMID- 16955161
TI  - [A study of highpull extraoral traction on the treatment of growing patients with
      skeletal Class II malocclusion].
AB  - PURPOSE: To evaluate the effect of highpull extraoral traction on growing
      patients with skeletal Class II malocclusion. METHODS: 11 pairs of cephalograms
      obtained before and after highpull extra-oral traction treatment were used in
      this study, treatment changes were measured with Pancherz analysis, and compared
      with the control group. Independent samples group t test with SPSS 11.0 software
      package was used for statistical analysis. RESULTS: highpull extra-oral traction
      had inhibitive effect on forward and downward maxillary growth. Changes on SNA, A
      Olp between the two groups were statistically different (P<0.01). Upper molars
      were moved back (P<0.01). CONCLUSION: highpull extraoral traction had orthopedic
      effect on the correction of skeletal Class II malocclusion of growing patients,
      including inhibition of maxillary growth and allowance of fully expression of
      mandibular growth. Meanwhile, dental-alveolar changes on the vertical and
      sagittal plane were beneficial to further improvement of the dental and facial
      appearance of the patients.

PMID- 16955162
TI  - [A histological innovative study of Balb/c mouse tooth germ transplanted to nude
      mouse in vivo].
AB  - PURPOSE: To observed the changes of the developed mouse's dental germs after
      transplanting into nude mouse and find some theoretical foundation for
      establishing an innovative experimental model. METHODS: Eight tooth germs from
      four 5th day postnatal Balb/c mice were transplanted to the back muscles of the
      adult nude mice. At seventh and fourteenth day after grafting, the germs were
      collected, fixed, demineralized, dehydrated, and embedded in wax. Serial sections
      of 5 microm thick were made following the routine methods, stained with
      haematoxylin-eosin dying solution, and observed under a light microscope. The
      mandibular first molars were taken out from the 12th and 19th day postnatal
      mouse. Serial sections of 5 microm thick were made following the routine methods,
      then compared with the germs after graft. RESULTS: All implantations were located
      in the superficial muscles with abundant capillary vessels. The dental germs
      could further developed after grafting under the microscope, but slower than
      dental germs self-development. The layer of dentin was thin, plenty of dentin
      with disorganized dentin tubule formed after grafting. Although the location of
      Hertwig's epithelial root sheath hardly moved, the roots developed further. The
      floor of pulp chamber could form and the pulp chambers were shrinking. The degree
      of calcification in the area of root increased very clearly. The inflammatory
      reaction was found at 7th day while hardly noted at 14th day after grafting.
      CONCLUSIONS: It suggests that late development of mouse tooth germs could further
      develop after heterotopic transplantation within the superficial muscles of the
      nude mouse. This model is useful for study of tooth root development in short
      time.

PMID- 16955163
TI  - [Expression of mineral-associated factors in the mineral stage tooth germ of
      mice].
AB  - PURPOSE: To study the distribution and expression of core binding factor alpha 1
      (Cbf alpha1), bone sialoprotein (BSP), osteopontin (OPN), osteocalcin (OC) and
      alkaline phosphatase (ALP) in mineral stage tooth germ of mice, so as to
      understand their roles in the development of the mineral stage tooth germ.
      METHODS: Thirty BALB/c mice in different days were killed, and their bilateral
      mandibular first molar germs with surrounding alveolar bone were taken out, then
      the tissues were fixed with 4% paraformaldehyde at 4 degrees C overnight,
      dehydrated, embedded in paraffin and serially sectioned at 5 microm.
      Immunohistochemical assay was adopted to determine the tissue distribution and
      cellular localization of Cbf alpha1, OPN, BSP, ALP and OC in the mineral stage
      tooth germ by these sections of BALB/c mice. RESULTS: There were Cbf alpha1, BSP
      and OPN expressing in the alveolar bone, and Cbf alpha1, ALP, OC in predentin,
      while in other tissues such as dental follicle, pulp cells, stratum intermedium,
      stellate reticulum, only ALP and OC were detected, but none of them were observed
      in the dentin. CONCLUSIONS: The formation mechanisms of hard tooth tissues are
      different. They are controlled by different factors. Cbf alpha1, ALP and OC are
      involved in the early formation of dentin, while Cbf alpha1, OPN and BSP involved
      in the early formation of alveolar bone, ALP involved in the stratum intermedium.
      They all play an important role in the start of mineralization.

PMID- 16955164
TI  - [Stress analyses and comparison of the Kennedy III dentition defect restored with
      removable partial denture].
AB  - PURPOSE: To investigate the stress distribution of the abutment and oral mucosa
      in Kennedy III, restored with removable partial dentures, either unilateral or
      bilateral designed. METHODS: Five FEA models were established for the partial
      edentulous and RPDs, which were divided into group A and group B. According to
      the denture design, bilateral (B) or unilateral (A) designed. The 3-D finite
      element analyses were proceeded and calculated with the help of the software
      ANSYS. Paired t test was used for statistical analysis using SAS 6.2 software
      package. RESULTS: The maximum stress appeared near the cervical mesial area of
      the first bicuspid and the second molar. There was no significant difference
      between the two groups in the stress distribution of the abutment and oral mucosa
      (P>0.05). CONCLUSION: In regard to the stress of the abutments, unilateral
      designs have no excess stress formed when RPD was used to restore Kennedy III
      dentition defect.

PMID- 16955165
TI  - [Establishment of a three-dimensional finite element model of mandible with
      dental implants for immediate loading].
AB  - PURPOSE: To establish a three-dimensional finite element model of mandible with
      dental implants for immediate loading, which will provide a basis for study of
      the biomechanical characteristics of the immediate loading implant-bone
      interface. METHODS: A female edentulous mandible was adopted for CT scanning, the
      scanned data were saved with the form of DICOM, and then input into compute.
      Universal Surgical Integration System which was developed by ourselves and ANSYS
      10.0 were used to divide mesh and establish finite element model. Three dental
      implants simulating the real shape of ITI thread implant were embedded in the
      anterior region of the mandible, of which implant-bone interface was granted with
      situation of smooth friction simulating the case of immediate loading. RESULTS:
      The accurate finite element model of mandible with dental implants for immediate
      loading was established, which included 127811 tetrahedron elements with 182252
      nodes. A single dental implant model comprised 13924 elements with 21420 nodes,
      the thread of it was continuous and smooth. CONCLUSION: The biomechanical
      similarity, the geometrical analogy and clinical indication of the model were
      quite good. The three-dimensional finite element model developed by this method
      can apply for precise analysis of the rule of biomechanics on the implant-bone
      interface for immediate loading.

PMID- 16955166
TI  - [Three-dimensional finite analysis of the application of attachment for
      restoration of unilateral maxillary defect].
AB  - PURPOSE: To study the stress of the application of attachment for restoration of
      unilateral maxillary defect. METHODS: Using the 3-D FE model of the unilateral
      maxillary defect, two different 3-D FE models of the application of attachment
      framework for restoration of different unilateral maxillary defects (attachment
      on the mesial side of the central incisor or canine) were designed and
      established. RESULTS: The area of stress concentration of the two prostheses were
      on the palatal base near the position of the anterior teeth. The stress was on
      the posterior teeth of the healthy side. When the attachment was on the mesial
      side of the central incisor, the stress of the mesial surface of the central
      incisor was 1.306MPa, and the stress concentration was at the junction of the
      attachment and the lingual guide plane. When the attachment was on the mesial of
      the canine, the stress of the mesial surface of the canine was 0.797MPa, and
      stress concentration was at the corner of the front and bottom of the lingual
      guide plane. CONCLUSIONS: The application of attachment for restoration of
      unilateral maxillary defect meets the biomechanical demands without increasing
      the stress load on the abutment. And further study of the design of the
      attachment framework should be done.

PMID- 16955167
TI  - [Early effects of the cyclic uniaxial compressive stress on Stress70/GRP75 in the
      rat condylar chondrocytes].
AB  - PURPOSE: The purpose of this study was to investigate the early effects of the
      cyclic uniaxial compressive stress on Stress70/GRP75 in the rat condylar
      chondrocyte. METHODS: The third-passage chondrocytes were harvested from the
      mandibular condyles of 2-day-old rats for this study, and a cellular compressive
      stress device (self-made four-point bending system, Patent No.01129166.4 &
      01256849.x) was used to apply stress on cells at 4000 microstrain (0.5 Hz
      frequency) for 0, 15, 30, 60, 120, 240 minutes respectively. The early effects of
      the cyclic uniaxial compressive stress on Stress70/GRP75 in the rat mandibular
      condylar chondrocytes were examined by Western blot and image analysis. One-way
      ANOVA was used for statistical analysis. RESULTS: The results showed that the
      expression of Stress70/GRP75 changed significantly with 4000 microstrain
      compressive stress loading. The gray scale value of protein band at 0 minute was
      114.2+/-5.08, significantly decreased to 86.1+/-5.09 (P<0.001) after 30 minutes,
      and then gradually increased to 104.0+/-4.41 (P<0.01) at 60 minutes. The
      expression of Stress70/GRP75 up-regulated to 134.5+/-3.74 (P<0.001) at 120
      minutes, and continued to increase within 240 minutes. CONCLUSION: There is time
      dependent response between the 4000 microstrain compressive stress stimulate and
      Stress70/GRP75. The expression of Stress70/GRP75 inhibited initially under the
      compressive stress, and then increased by feedback with the increased loading
      time.

PMID- 16955168
TI  - [The construction and analysis of three-dimensional finite element model of human
      unilateral maxillary defect].
AB  - PURPOSE: To built a three-dimensional finite element model of the common
      unilateral maxillary defect, and to study the stress of the traditional
      maxillofacial prostheses for unilateral maxillary defect. METHODS: The three
      dimensional finite element model of unilateral maxillary defect and maxillofacial
      obturator prosthesis were constructed by means of spiral CT scanning, digital
      image transfer, self-developed software MedGraphics, UG engineering design
      program and ANASYS software. Then 3-D finite element stress analysis was carried
      out, for the prosthesis. RESULTS: The three-finite element models of the
      unilateral maxillary defect and maxillofacial obturator prosthesis were
      established. In the traditional obturator prosthesis, the stress was on the
      posterior teeth of the healthy side; the area of stress concentration was on the
      palatal base near the position of the anterior teeth. CONCLUSIONS: The three
      dimensional finite element models of the unilateral maxillary defect and
      maxillofacial obturator prosthesis have good similarity in geometry and biology.
      The obturator prosthesis is in accorded with the biomechanical demands.

PMID- 16955169
TI  - [Effects of chitosans with different molecular weights on Streptococcus sanguis
      biofilm].
AB  - PURPOSE: To investigate the effects of chitosan on Streptococcus sanguis biofilm.
      METHODS: Streptococcus sanguis biofilm was formed on saliva-coated glass (SCG) in
      a flow culture system, then exposed to 2% chitosans with different molecular
      weights (5 cps, 80 cps, 600 cps) for 3, 10, 30 minutes. Confocal laser scanning
      microscope and Vital/Dead fluorescent staining technique (vital stained green,
      dead stained red) were combined to observe the biofilm thickness, bacterial
      density. Analysis of variance was used for comparison. RESULTS: The biofilm
      thickness and bacterial density reduced significantly after treatment by 2%
      chitosan. Of all the treatment groups, 5 cps (low molecular weight) chitosan is
      most effective (P<0.01). CONCLUSIONS: 5 cps (low molecular weight) chitosan seems
      to be most effective in detaching biofilm.

PMID- 16955170
TI  - [Establishing three-dimensional reconstruction and measuring system for complete
      denture occlusion].
AB  - PURPOSE: This study was designed to investigate the digital method of locating
      and reconstructing the occlusal relationship between the upper and lower full
      dentures. METHODS: The artificial teeth occlusal surfaces of ten complete
      dentures were scanned by non-contact laser scanner and were reconstructed by
      three-dimensional technique. With placements of 6 standard steel ball, the three
      dimensional position relationship of upper and lower full dentures were studied
      and reconstructed in centric occlusal position. RESULTS: The three-dimensional
      reconstruction and measuring system of complete denture occlusion was
      preliminarily established in this study. CONCLUSIONS: This study focused on
      exploiting a new system to quantitatively reconstruct the occlusal relationship
      of complete denture in centric occlusion. And the study may set a methodological
      foundation of further three-dimensional research for complete denture occlusion.

PMID- 16955171
TI  - [A comparison between the cast-bonded keeper with different dental alloys in the
      metallographic structure].
AB  - PURPOSE: The aim of this study is to investigate the changes of the
      metallographic structure of the cast-bonded keeper when cast in varied
      temperatures. METHODS: Three groups were included in this study: the gold alloy
      group, the Ni-Cr alloy group and Ti group, with the Magdisc 500 keeper as the
      control group. Each sample that contained a Magdisc 500 keeper was fabricated
      with the cast-bonded technique. Then, the samples were fabricated into a
      metallographic sample by polishing, smoothing and cleaning. Each sample was
      observed under metallographic microscope. RESULTS: There were no significant
      changes in the crystal size between the keeper in the gold alloy group and that
      in the control group. In both of the Ni-Cr alloy group and Ti group, the crystal
      of the keeper became larger, and this was more evident in the latter group.
      CONCLUSION: The keeper varied in the metallographic structure if cast-bonded with
      gold alloy, Ni-Cr alloy or Ti metal. The higher the casting temperature, the
      larger the crystal of the keeper. The results suggest that the change in the gold
      group is less than that in the Ni-Cr alloy group and Ti metal group.

PMID- 16955172
TI  - [The influence of heat/pressure polymerization method on the adaptation of
      complete denture base].
AB  - PURPOSE: The purpose of this in vitro study is to investigate the mechanical
      ability and adaptation of complete denture base by the use of thermoformed resin
      cured with heat/pressure injection method. METHODS: The flexural strength, the
      surface hardness and the adaptation of thermoformed resin and SR Ivoclar capsule
      resin were compared between using the conventional water bath-cured method and
      heat/pressure injection method. The collected date were analyzed statistically
      using the two-sample t test at alpha=0.05. RESULTS: The thermoformed resin cured
      with heat/pressure injection method has significant difference from that cured
      with conventional water bath-cured method on flexural strength and surface
      hardness (P<0.05). The upper partial base had significant difference in the gap
      distance at point A, B, D and E (P<0.05) between the thermoformed denture base
      cured with heat/pressure injection method and conventional water bath-cured
      method. CONCLUSIONS: These findings indicate that the thermoformed resin cured
      with heat/pressure injection method has better mechanical abilities and
      adaptation than that cured with conventional water bath-cured method.

PMID- 16955173
TI  - [Characters of the surface of the cast-bonded keeper: an experimental study].
AB  - PURPOSE: This study is aimed to analyze the characters of the surface of the
      keeper after cast-bonded in varied temperatures. METHODS: Twelve keepers were
      divided into three groups: the gold alloy group, the Ni-Cr alloy group and the Ti
      group with four samples in each group. A sample that contained a Magdisc 500
      keeper was fabricated with the cast-bonded technique. Then, the surface of the
      sample was observed under scanning electron microscope (SEM) and its elements
      were analyzed with the electron probe. RESULTS: The results showed that there was
      no oxide film on the surface of the keeper in the gold alloy group and the Ni-Cr
      alloy group, but there was an oxide film on the surface of the keeper in the Ti
      group. However, remains of the investment materials were found on the surface of
      the sample of three groups. CONCLUSIONS: The study suggested that the casting
      temperature affect the characters of the surface of the cast-bonded keeper. Gold
      alloy or Ni-Cr alloy is of better properties for clinical use.

PMID- 16955174
TI  - [The effects of different welding wires on the mechanical properties of laser
      welding joints].
AB  - PURPOSE: To evaluate the mechanical properties and microstructure of laser-welded
      joints with different welding wires for clinical use of welding wire. METHODS:
      The standard tensile test and three-point bending test rods were made from Co-Cr
      and Ni-Cr alloy, and were laser-welded with different welding wire (commercially
      welding wire and casting wire). Then the tensile rods were tested for the
      ultimate tensile strength (UTS), and the bending rods for the ultimate bending
      strength (UBS). The results was analyzed by one-way ANOVA. The tensile fracture
      surface were examined by scanning electron microscopy (SEM). Metallurgical
      analysis were also performed on polished longitudinal sectioned samples. RESULTS:
      For Co-Cr alloy, the UTS of casting wire group and commercially welding wire
      group was respectively (606.40+/-82.53)MPa and (693.61+/-47.68)MPa; the UBS was
      respectively (997.95+/-88.89)MPa and (1160.76+/-91.59)MPa. ANOVA showed a
      significant difference of UTS and UBS between the two groups at the 0.05 level
      (P<0.05). For Ni-Cr alloy, the UTS of casting wire group and commercially welding
      wire group was respectively (558.14+/-46.75)MPa and (582.32+/-35.43)MPa; the UBS
      was respectively (1084.75+/-46.02)MPa and (1078.29+/-36.25)MPa. There was no
      significant difference between the two groups (P>0.05). SEM and metallurgical
      examination showed the welded zone exhibiting more cracks in the casting wire
      group than in the commercially welding wire group. CONCLUSION: It would be
      advisable to work with commercially welding wire for the joints that need better
      strength.

PMID- 16955175
TI  - [Comparison of the difference of the magnetic force by cast post-keepers combined
      with three different metals].
AB  - PURPOSE: Three different metals were used to make cast post-keepers of magnetic
      attachment. The magnetic force was tested and analyzed. METHODS: The cast-post
      keepers were combined by gold alloy, Ni-Cr alloy and Ti metal respectively. 12
      samples were divided into three groups, 4 in each. Root surface structures were
      manufactured by these samples. The values of the magnetic force of the magnetic
      attachment were tested and compared using ANOVA. RESULTS: The average value of
      the attractive force of the keeper combined by gold alloy was 4.84N, while that
      of the keeper combined by Ni-Cr alloy was 4.61N and the keeper combined by Ti was
      4.12N. Significant difference was found between each two samples, P<0.01.
      CONCLUSION: The magnetic force of the keepers combined by three different metals
      decreased to certain degrees, the keeper combined by gold alloy decreased the
      least.

PMID- 16955177
TI  - [Orthodontic treatment for the impacted upper central incisors: report of 28
      cases].
AB  - PURPOSE: To study the effect of treating the impacted upper central incisors
      which couldn't erupt by surgical exposure and orthodontic traction. METHODS: 28
      cases with 30 impacted upper central incisors were treated with surgical exposure
      and orthodontic traction. RESULTS: In 1 case, the tooth erupted by traction. but
      the space was not enough, the child's parents refused extraction of the teeth,
      which resulted in malalignment of the maxillary incisors. In 1 case, the tooth
      erupted after 3 months of traction, but the patient gave up further treatment
      because he had no revisit time. In the remaining 26 cases all the teeth moved
      into correct position. The average eruption time was 4.5 month (rang: 1 to 10
      months). 28 impacted teeth had vital pulp. No root absorption and conglutination
      were found. CONCLUSIONS: The time of treatment, reasonable orthodontic method,
      less operative trauma, appropriate traction force, anchorage, control of
      inflammation are the keys of successful treatment.

PMID- 16955176
TI  - [Inhibition of extracts from 17 Chinese herbs on periodontal pathogenic
      microbes].
AB  - PURPOSE: To evaluate the efficiency of 17 Chinese herbs on periodontal pathogenic
      microbes. METHODS: 17 efficient substances from Chinese herbs were purchased from
      Chinese Drug Identification Bureau, including magnesium lithospermate B,
      magnolol, tetramethyl pyrazine, matrine, dycyrrhizin, gentiopicrin, aloperin,
      baicalin, oleanolic acid, ginkgo seed, total glucosides of paeony capsules,
      anisldehyde, archin, cablin patchouli, hydrochloric acid Berberine, forsythin,
      and kakonein. Antimicrobial sensitivity tests of broth microdilution methods on
      96-microwell plate were carried out for identification of the antimicrobial
      activity of extracts against six species of microorganisms: Actinobacillus
      actinomycete mitans(Aa) Y4, Actinomycetes viscosus(Av) 19246, Porphyromonas
      gingivalis(Pg) 33277, Fusobacterium necrophorum(Fn) 25286, Actinomyces
      naeslundii(An) wvl 45 and Prevotella nigrescens(Pn). RESULTS: It was found that
      magnesium lithospermate B and magnolol showed the most efficient inhibition on
      microorganism of Pn and Fn, with the MIC being 0.053 and 0.313 mg/ml for Pn and
      Fn, respectively. Tetramethyl pyrazine, matrine, dycyrrhizin, gentiopicrin,
      aloperin, baicalin, and oleanolic acid had better inhibition than total
      glucosides of paeony capsules, anisldehyde, archin, cablin patchouli,
      hydrochloric acid berberine, forsythin, and kakonein. CONCLUSION: The Chinese
      herbs, magnesium lithospermate B and magnolol are efficient agents for inhibition
      against periodontal pathogenic microbes.

PMID- 16955178
TI  - [Clinical effect of treatment of primary molar teeth with extensive defect using
      prefabricated metal crowns].
AB  - PURPOSE: To observe the clinical effect of treatment of primary molar teeth with
      extensive defect using prefabricated metal crowns (PMCs). METHODS: 66 cases, 73
      primary molar teeth with extensive defect (class I-III), which can not be
      repaired by amalgam restoration efficiently, were treated by means of PMCs, and
      were followed up regularly for 18 months. Chi-square test was used for
      statistical analysis by SPSS10.0 software package. RESULTS: 18 months after
      treatment,a total successful rate of 86.30% was achieved, with successful rates
      of 89.27%, 92.86%, 70.59% for class I-III respectively. Chi(2)=4.779, P=0.092
      (P>0.05), there was no significant difference in the effect among the three types
      using PMCs. CONCLUSION: The clinical effect of the treatment of primary molar
      teeth with extensive decay using PMCs is satisfactory. In order to enhance the
      successful rate, it is necessary to restore the decayed teeth prior to using
      PMCs, control the amount of occlusal reduction, and crimp as required to adapt to
      gingival margin for snug fit.

PMID- 16955179
TI  - [Supernumerary teeth: report of a rare case and review of the literature].
AB  - Supernumerary teeth is a well-recognized clinical phenomenon. Multiple
      supernumerary teeth are commonly associated with variable syndromes. However the
      multiple supernumerary teeth reported in mandibular and maxilla premolar region
      of an 14-year-old female patient without any associated systemic
      condition/syndrome is a rare case. A review of the literature relating to
      supernumerary teeth is presented including possible presentations, diagnostic
      features and treatment options.

PMID- 16955180
TI  - [Case report of enterobrosis and diffuse peritonitis caused by a swallowed
      removable partial denture].
AB  - A female patient, aged 62 years, unexpectedly swallowed a removable partial
      denture (RPD) during the supper. The doctor failed to take out the RPD from her
      stomach under the gastroscope during the emergency treatment at the first day. 2
      days later, the PRD blocked the intestinal tract and its metal clasps penetrated
      the wall of the intestine near the ileocecal junction, it soon leaded to
      enterobrosis and diffuse peritonitis. At last, abdominal operation was conducted
      to take the RPD out from the intestine and enterobrosis was patched up
      successfully. Diffuse peritonitis was also cured by intravenous infusion of
      antibiotics for about 1 week.

PMID- 16955181
TI  - Glucocorticoid-induced tumour necrosis factor receptor (GITR) and its ligand
      (GITRL) in atopic dermatitis.
AB  - The glucocorticoid-induced tumour necrosis factor receptor-related gene (GITR) is
      expressed on regulatory T-cells (Treg), which are CD4+CD25+ lymphocytes. Binding
      of the GITR-ligand (GITRL) leads to downregulation of the regulatory function of
      Tregs. Patients suffering from a defect in their Tregs exhibit a condition in
      their skin resembling atopic dermatitis. GITR also exists in a soluble form, and
      increased levels of this lead to decreased levels of GITRL and thereby increased
      Treg activity. We have measured the levels of GITR and GITRL in plasma from
      atopic dermatitis patients and found it not to be increased. Furthermore, plasma
      levels of GITR and GITRL did not correlate with SCORAD. Both GITR and GITRL
      correlated with the levels of thymus- and activation-regulated chemokine/CCL17
      and cutaneous T-cell-attracting chemokine/CCL27, two chemokines believed to play
      a major role in the pathogenesis of atopic dermatitis and the migration of Tregs
      and skin-homing T-cells. Immunohistochemistry showed GITR and GITRL were present
      in few dermal cells of both patients with atopic dermatitis, and normal healthy
      volunteers, and often localized in close proximity to each other. Since
      regulatory T-cells are localized in the vicinity of GITRL-expressing cells in
      atopic dermatitis skin, the GITR/GITRL interaction may serve to perpetuate the
      inflammation locally.

PMID- 16955182
TI  - Electrical ear acupuncture reduces histamine-induced itch (alloknesis).
AB  - In order to assess an objective measure for the outcome of ear acupuncture, we
      evaluated the effect of electrical ear acupuncture on areas of histamine-induced
      alloknesis in 32 healthy volunteers. In a first assessment 5 min after histamine
      application on both volar forearms, 16 subjects received right ear and 16 left
      ear acupuncture. Immediately before and 5 min after acupuncture, alloknesis areas
      on both forearms were planimetrically evaluated. A second assessment was carried
      out 4 weeks later with the same patients. They underwent histamine application
      once more, but received no acupuncture. Alloknesis areas were then compared with
      reference to time, assessment and therapy side. Forearms relating to ipsilateral
      acupuncture showed significantly reduced or even no alloknesis areas after
      therapy. On the contralateral sides and during the "non-acupuncture" assessment 4
      weeks later, alloknesis areas were significantly enlarged compared with sides
      ipsilateral to right and left ear acupuncture. Hence, results verify the effects
      of electrical ear acupuncture by objective measures.

PMID- 16955183
TI  - Important factors for pain during photodynamic therapy for actinic keratosis.
AB  - Photodynamic therapy (PDT) is an efficient treatment for actinic keratosis. A
      common problem, however, is pain. The aim of this study was to investigate pain
      during PDT for actinic keratosis. The possibility of using capsaicin cream for
      pain relief was also assessed. Pain was investigated during aminolaevulinic acid
      PDT in 91 patients. Size, redness, scaling and induration of the lesions were
      recorded. Maximum pain during treatment was registered, using a visual analogue
      scale (0-10). The pain-reducing efficacy of capsaicin was tested in a pilot study
      in six patients (10 lesions). These patients were pre-treated with capsaicin
      cream for one week before commencing PDT. Pain was found to be normally
      distributed around a mean value of visual analogue scale 4.6. Larger lesions gave
      more pain (p=0.001). The redness of the actinic lesions was found to be related
      to PDT-induced pain (p=0.01), the reduction of actinic area (p=0.007), and the
      cure rate (p=0.01). The redder the actinic area, the better the treatment outcome
      and the more pain experienced. Patients with the largest reduction in the actinic
      area experienced more pain (p=0.053). The most important factors for presence of
      pain seem to be the size and the redness of the lesion. No significant pain
      relief was experienced after pre-treatment with capsaicin.

PMID- 16955184
TI  - Morphine gel 0.3% does not relieve pain during topical photodynamic therapy: a
      randomized, double-blind, placebo-controlled study.
AB  - There is a demand for pain relief during photodynamic therapy. We therefore
      investigated the efficacy and side-effects of topical morphine gel 0.3% for pain
      relief during topical photodynamic therapy in a randomized, double-blind, placebo
      controlled study. The study involved 28 patients with actinic keratoses or basal
      cell carcinomas. Each patient was treated with photodynamic therapy after
      superficial curettage of 2 treatment areas that were randomized to morphine gel
      or placebo gel. The gels were applied 15 min before illumination. Pain was
      assessed pre-illumination, during, and immediately after illumination, using a
      numeric rating scale. Skin redness was determined by reflectance
      spectrophotometry and the size of the treated area by protoporphyrin IX
      fluorescence. There were no differences between the areas according to
      accumulation of protoporphyrin IX (p =0.34), size of fluorescence areas (p
      =0.84), or skin redness (p =0.95). There was no significant pain relief of
      topical morphine gel compared with placebo gel (p >0.23). This negative result
      suggests that opioid receptors may not be involved in the pain induced by
      photodynamic therapy.

PMID- 16955185
TI  - Topical 5-aminolevulinic acid mediated photodynamic therapy of superficial basal
      cell carcinoma using two light fractions with a two-hour interval: long-term
      follow-up.
AB  - Photodynamic therapy (PDT) of superficial basal cell carcinoma using topical 5
      aminolaevulinic acid (ALA) and 75-100 J/cm2 light dose yields unsatisfactory long
      term results. In several animal models, illumination with two light fractions
      approximately 2 h apart was considerably more effective than single illumination,
      suggesting the need for a pilot clinical study. Fifteen patients with a total of
      86 primary superficial basal cell carcinomas, received topical ALA and were
      illuminated 4 and 6 h later, both with 45 J/cm2 laser light (633+/-1 nm).
      Fluorescence spectra were measured before and immediately after each
      illumination. At a mean follow-up of 59 months (range 44-82), 67 lesions could be
      evaluated, 56 of which showed a complete response (84%). Cosmesis was
      good/excellent in 88% of the complete response group and fair in 12%. There was
      no correlation between protoporphyrin fluorescence and response, but a
      significant correlation between the percentage of fluorescence left after
      photobleaching by the first illumination and the amount of protoporphyrin re
      synthesized 2 h later. In conclusion, the long-term complete remission rate of
      fractionated ALA-mediated PDT of superficial basal cell carcinoma as reported
      here is significantly better than after PDT with single illumination previously
      reported by others, but equal to studies using single illumination with a much
      higher light fluence. Further improvement may be possible by reducing the fluence
      of the first fraction, with constant total fluence.

PMID- 16955186
TI  - Penile intraepithelial neoplasia: results of photodynamic therapy.
AB  - Failure of response to treatment or recurrent disease is often noted in patients
      with penile intraepithelial neoplasia. Photodynamic therapy has recently been
      added to the list of treatment modalities used for this diagnosis. Our primary
      objective was to study the results of photodynamic therapy in the treatment of
      penile intraepithelial neoplasia in men over the age of 40 years. Ten patients
      aged 42-82 years with histopathologically confirmed lesions were studied. Lesions
      initially responded to photo-dynamic therapy in 7 out of 10 patients. Four of
      these patients presented no recurrences during a mean follow-up of 35 months, and
      were completely cleared after 2-8 treatments (mean 4.5 treatments). Three
      patients presented recurrences after treatment. No patient developed invasive
      penile cancer (mean follow-up 46.5 months). Photodynamic therapy is an
      alternative in the treatment of penile intraepithelial neoplasia, although
      prospective randomized trials are required to provide therapeutic guidelines.

PMID- 16955187
TI  - Inosiplex for treatment of alopecia areata: a randomized placebo-controlled
      study.
AB  - Treatment of alopecia areata remains unsatisfactory. We decided to test if
      systemic therapy with inosiplex (Isoprinosine(R)), an immunomodulator could
      influence the disease. Thirty-two subjects with recalcitrant alopecia areata,
      aged 16-48 years (mean 30.3+/-5.1 years), were randomized into two treatment
      groups of 16 subjects each. They were assigned to receive either oral inosiplex
      (group 1), or placebo (group 2) on a double-blind basis. Inosiplex dosage was 50
      mg/kg/day in five divided doses for 12 weeks. Of the 15 evaluable patients in
      group 1, 5 (33.3%) had full remission, 8 (53.3%) responded partially and 2
      (13.3%) did not respond. Of the 14 evaluable patients in the placebo group, none
      had full remission, 4 (28.5%) responded partially and 10 (71.4%) did not respond.
      The therapeutic difference between patients receiving active and placebo therapy
      was statistically significant (?2=7.82, p<0.01). Compared with placebo, oral
      inosiplex showed considerable efficacy in alopecia areata with insignificant side
      effects. Larger studies are required, however, before inosiplex may be
      recommended as an efficacious and safe alternative systemic form of therapy for
      recalcitrant alopecia areata.

PMID- 16955188
TI  - Prevalence of toe nail onychomycosis in diabetic patients.
AB  - Onychomycosis among diabetic patients has been reported in some studies to be of
      high prevalence. This study aimed to investigate the prevalence of onychomycosis
      among diabetic patients at a Danish University Hospital. Clinical and mycological
      examinations were performed on type 1 and 2 diabetic patients from in- and out
      patient clinics. A total of 271 patients were enrolled, 72% males, mean age 61.3
      years, 26% of the patients had diabetes type 1. The prevalence of toe nail
      onychomycosis (positive culture and/or microscopy) was 22% (n = 59) of which 55
      cases were caused by dermatophytes (93%) and 4 cases by yeasts (7%). A
      correlation was found between onychomycosis and age (p =0.02) and severity of
      nail changes (p <0.001), respectively. However, no significant correlation was
      found to gender, type of diabetes, lower extremity arterial disease, neuropathy,
      toe amputation or oedema. Onychomycosis occurred with a high prevalence in
      diabetic patients, especially among older patients and those with severe nail
      changes.

PMID- 16955189
TI  - Pulse methylprednisolone therapy for threatening periocular haemangiomas of
      infancy.
AB  - Periocular haemangiomas of infancy can cause severe and rapid ocular damage. Oral
      corticosteroids remain the front-line treatment to minimize the consequences of
      these haemangiomas. The aim of this report is to summarize our experience with
      pulse intravenous methylprednisolone as an alternative therapy for periocular
      haemangioma when visual prognosis is engaged. Fifteen infants, who presented
      periocular haemangioma with functional impact on vision, received 2 mg/kg
      methylprednisolone intravenously twice a day for 2 days. Following pulse therapy,
      2 mg/kg/day prednisolone was given orally with gradual tapering. No further
      visual impact was noticed following pulse therapy. Two patients relapsed, needing
      new pulses or, in one case, vincristine. No serious side-effects were recorded.
      Pulse methylprednisolone therapy permitted a particularly rapid shrinkage of
      haemangiomas and a complete disappearance of their visual impact within 2 days.
      Apparently more rapid than the usual oral corticosteroids, pulse intravenous
      methylprednisolone decreases the risk of ocular complications, which correlates
      with the duration of the influence of haemangiomas.

PMID- 16955190
TI  - Unexpectedly high frequency of genital involvement in women with clinical and
      histological features of oral lichen planus.
AB  - The main aims of this cross-sectional study were: (i) to assess the frequency of
      genital (vulval) lichen planus (VLP) and vulval lichen sclerosus (VLS) in women
      affected with oral lichen planus (OLP), regardless of the genital symptoms
      reported; and (ii) to verify whether any demographic, clinical, or histological
      features of OLP are associated with a higher risk of vulvo-vaginal involvement.
      Fifty-five women, presenting OLP, consecutively underwent gynaecological
      examination and, if they demonstrated positive clinical signs of VLP, underwent
      biopsy. After a drop-out of 14 subjects, 31/41 (75.6%) were found to have signs
      of genital involvement, of which 13/31 (44.0%) were asymptomatic. Following
      genital biopsy, 27/31 (87.1%) had histologically confirmed VLP or VLS. Following
      both univariate and multivariate statistical analyses, no significant association
      was found between gynaecological concomitance and demographic, clinical,
      histological features of OLP. This unpredictably common genital involvement in
      females with OLP emphasizes the importance of routinely performing both oral and
      gynaecological examinations, to facilitate an early and correct therapeutic
      approach.

PMID- 16955191
TI  - Genital ulcers as initial manifestation of Epstein-Barr virus infection: two new
      cases and a review of the literature.
AB  - Genital ulceration is an uncommon manifestation of primary Epstein-Barr virus
      (EBV) infection. We present here two cases of genital ulcers probably caused by
      EBV. The first case is a 12-year-old girl with a genital ulcer appearing before
      specific EBV serology could identify a primary infection. However, serology was
      positive 13 days after the ulcer appeared. Polymerase chain reaction for EBV was
      positive in the biopsy from the ulcer as well. The second case is an 18-year-old
      female in whom the specific EBV serology was positive 8 days after appearance of
      the ulcer. The ulcers in both cases healed after 21 days. We reviewed the
      literature and a total of 26 cases of EBV-associated genital ulcers in females
      are now published. Median age of the 26 cases is 14.5 years of whom only 6
      reports previous sexual contact. Mean healing time for the ulcers is 18 days. Our
      two cases correspond well with clinical reports of 24 EBV-associated genital
      ulcers in the literature.

PMID- 16955192
TI  - Penicillin-induced anti-p200 pemphigoid: an unusual morphology.
AB  - We report here a case of a 52-year-old woman with erythema gyratum repens-like
      lesions appearing during anti-p200 pemphigoid, probably induced by oral
      penicillin. The diagnosis of anti-p200 pemphigoid was made by the presence of in
      vivo bound and circulating IgG anti-basement membrane zone auto-antibody reactive
      with the dermal side of salt-split skin and with 200 kDa protein in dermal
      extract on Western immunoblot. Laser scanning confocal microscopic study
      disclosed the localization of IgG at the lamina lucida-lamina densa border. Skin
      lesions responded poorly to high dose of prednisone and the combination of
      prednisone and dapsone. When methotrexate was added, skin lesions healed within 3
      weeks. To our knowledge, erythema gyratum repens-like lesions have not been
      described previously in this disorder. Thus, we have expanded the clinical
      morphological spectrum of patients with anti-p200 pemphigoid and first described
      a patient whose disorder was probably drug-induced.

PMID- 16955193
TI  - Intrinsic atopic dermatitis is associated with a beta-2 adrenergic receptor
      polymorphism.

PMID- 16955194
TI  - Oral corticosteroids did not prevent AGEP due to terbinafine.

PMID- 16955195
TI  - Hydroxychloroquine in psoriasis: is it really harmful?

PMID- 16955196
TI  - Bamboo spine mimicking Bekhterev's disease caused by long-term acitretin
      treatment.

PMID- 16955197
TI  - Depot leuprorelin acetate-induced granulomas manifested as persistent suppurative
      nodules.

PMID- 16955198
TI  - Severe exacerbation of psoriatic arthritis during treatment with efalizumab. A
      case report.

PMID- 16955199
TI  - Primary non-essential cutis verticis gyrata revealed with 3-D magnetic resonance
      imaging.

PMID- 16955200
TI  - Keratoacanthoma-like cutaneous metastasis of lung cancer: a learning point.

PMID- 16955201
TI  - Chemical burns to the scalp from hair bleach and dye.

PMID- 16955202
TI  - Multiple panniculitis caused by Actinobacillus and Actinomyces infections.

PMID- 16955203
TI  - Human papilloma virus testing of vaginal smear obtained with a novel self
      sampling device.

PMID- 16955204
TI  - Pemphigus vulgaris induced by honeybee sting?

PMID- 16955205
TI  - Additional test evaluating the psychosocial status of psoriasis patients.

PMID- 16955206
TI  - 4th Georg Rajka International Symposium on Atopic Dermatitis. Meeting report.

PMID- 16955207
TI  - Insulin-like growth factor I: a predictor of long-term glucose abnormalities in
      patients with acute myocardial infarction.
AB  - AIMS/HYPOTHESIS: Low levels of IGF-I are associated with increased risk of
      cardiovascular disease and type 2 diabetes. The aim of this study was to
      investigate the IGF-I system in patients with acute myocardial infarction (AMI)
      without previously known diabetes. MATERIALS AND METHODS: One hundred and sixty
      eight AMI patients were classified before hospital discharge by means of an OGTT
      as having NGT, IGT or newly detected type 2 diabetes. Age- and sex-matched
      subjects from the background population (n=185) served as the control group. The
      associations between fasting levels of IGF-I and IGF binding proteins 1 and 3
      (IGFBP-1, IGFBP-3) and glucose metabolism during a follow-up period of 12 months
      were studied. RESULTS: At hospital discharge, age-adjusted IGF-I (IGF-I SD) was
      significantly lower in patients with abnormal glucose tolerance (AGT=IGT or type
      2 diabetes) compared with patients with NGT (p=0.014) and control subjects
      (p<0.001). IGF-I was strongly correlated with IGFBP-3 (r=0.730, p<0.001), which
      was significantly lower in patients with AGT compared with patients with NGT
      (p=0.009) and control subjects (p<0.001). Fasting levels of IGFBP-1 did not
      differ significantly between patients with NGT and AGT or between patients and
      control subjects. In a multiple logistic regression analysis in patients, IGF-I
      at hospital discharge was a significant predictor of AGT at discharge and after
      12 months (adjusted odds ratio 0.29, p=0.022, and adjusted odds ratio 0.29,
      p=0.034, respectively). CONCLUSIONS/INTERPRETATION: Low levels of IGF-I may be a
      useful predictor of abnormal glucose metabolism in patients with AMI.

PMID- 16955208
TI  - Low cumulative incidence of proliferative retinopathy in childhood-onset type 1
      diabetes: a 24-year follow-up study.
AB  - AIMS/HYPOTHESIS: We estimated cumulative incidence of proliferative diabetic
      retinopathy (PDR) and risk factors for developing diabetic retinopathy (DR) in
      childhood-onset type 1 diabetes. MATERIALS AND METHODS: A sample of 294 patients
      with childhood-onset type 1 diabetes (<15 years) diagnosed in Norway between 1973
      and 1982 was examined for retinopathy at baseline between 1989 and 1990 and at
      follow-up from 2002 to 2003. At follow-up, mean age was 33 years (range: 21-44),
      mean diabetes duration 24 years (19-30) and total person-time contributed 7,152
      person-years. Retinal photographs were taken at baseline and follow-up.
      Associations between baseline factors and PDR were estimated using Cox regression
      models. RESULTS: Overall, 262 of 294 (89.1%) developed DR from diabetes onset, of
      whom 31 developed PDR. The 25-year cumulative incidence of PDR was 10.9% (95% CI
      7.3-14.5). Among 194 without retinopathy at baseline, 163 (84%) developed DR and
      nine (5%) progressed to PDR. Among 97 patients with non-proliferative DR at
      baseline, 19 (20%) progressed to PDR. Significant predictors for developing PDR
      were retinopathy at baseline (relative risk [RR]=3.71, 95% CI 1.59-8.68), HbA(1c)
      (RR=2.05, 1.44-2.93), and triglycerides (RR=1.55, 1.06-1.95).
      CONCLUSIONS/INTERPRETATION: Nine out of every ten patients diagnosed with type 1
      diabetes developed DR, but only one out of ten developed PDR within their first
      25 years of diabetes duration. The cumulative incidence of PDR is lower than
      previously reported from other countries. Potentially modifiable risk factors
      predict the development of DR and PDR.

PMID- 16955209
TI  - Association between variants in the genes for adiponectin and its receptors with
      insulin resistance syndrome (IRS)-related phenotypes in Mexican Americans.
AB  - AIMS/HYPOTHESIS: The aim of this study was to examine whether genetic variation
      in ADIPOQ, ADIPOR1 and ADIPOR2 may contribute to increased susceptibility to
      components of the insulin resistance syndrome (IRS). MATERIALS AND METHODS: We
      genotyped single-nucleotide polymorphisms (SNPs) in ADIPOQ, ADIPOR1 and ADIPOR2
      in Mexican American subjects (N=439) and performed an association analysis of IRS
      related traits. RESULTS: Of the eight SNPs examined in the ADIPOQ gene, rs4632532
      and rs182052 exhibited significant associations with BMI (p=0.029 and p=0.032),
      fasting specific insulin (p=0.023 and p=0.026), sum of skin folds (SS) (p=0.0089
      and p=0.0084) and homeostasis model assessment of insulin sensitivity (HOMA-%S)
      (p=0.015 and p=0.016). Two other SNPs, rs266729 and rs2241767, were significantly
      associated with SS (p=0.036 and p=0.013). SNP rs7539542 of ADIPOR1 was
      significantly associated with BMI, SS and waist circumference (p=0.025, p=0.047
      and p=0.0062). Fourteen of the ADIPOR2 SNPs were found to be significantly
      (p<0.05) associated with fasting plasma triglyceride concentrations. Four of
      these SNPs (rs10848569, rs929434, rs3809266 and rs12342) were in high pairwise
      linkage disequilibrium (r (2)=0.99) and were strongly associated with fasting
      triglyceride levels (p=0.00029, p=0.00016, p=0.00027 and p=0.00021). Adjusting
      for the effects of BMI and HOMA-%S on triglyceride concentrations increased
      significance to p=0.000060 for SNP rs929434. Bayesian quantitative trait
      nucleotide analysis was used to examine all possible models of gene action.
      Again, SNP rs929434 provided the strongest statistical evidence of an effect on
      triglyceride concentrations. CONCLUSIONS/INTERPRETATION: These results provide
      evidence for association of SNPs in ADIPOQ and its receptors with multiple IRS
      related phenotypes. Specifically, several genetic variants in ADIPOR2 were
      strongly associated with decreased triglyceride levels.

PMID- 16955210
TI  - Protection from inflammatory disease in insulin resistance: the role of mannan
      binding lectin.
AB  - AIMS/HYPOTHESIS: Decreased sensing of the innate immune system may lead to
      chronic activation of the inflammatory cascade. We hypothesised that mannan
      binding lectin (MBL) deficiency may confer risk of obesity and insulin
      resistance. MATERIALS AND METHODS: We performed a cross-sectional study of MBL
      protein concentration (n=434) and MBL2 gene mutations (exon 1) (n=759) in
      association with obesity, markers of inflammation and insulin action (euglycaemic
      clamp, n=113), and a longitudinal study of MBL protein before and after weight
      loss in obese patients (n=10). We also studied the effects of MBL in vitro in
      muscle cells and circulating MBL-A (mouse equivalent of human MBL) in a mouse
      model. RESULTS: Among 434 consecutive non-diabetic men, the age-adjusted serum
      MBL concentration was lower in obese subjects than in lean subjects (median: 959
      microg/ml [interquartile range: 116.8-2,044 microg/ml] vs 1,365 [467-2,513]
      microg/ml; p=0.01) and was accompanied by increased serum inflammatory markers.
      Insulin action correlated significantly with serum MBL (r=0.49, p<0.0001). Serum
      MBL concentration increased by a median of 110.2% after weight loss. The change
      in serum concentration of MBL was positively associated with the increase in
      insulin sensitivity (r=0.713, p=0.021). At least one MBL2 gene mutation was
      present in 48.2% of obese vs 39.3% of non-obese subjects (p=0.037). The plasma
      concentration of MBL-A was lower in insulin-resistant obese ob/ob mice, as was
      the glucose/insulin ratio. Incubation of rat soleus muscle with human MBL
      markedly increased fatty acid oxidation. CONCLUSIONS/INTERPRETATION: These
      findings suggest that MBL, previously thought only to be involved in inflammation
      and immune system function, affects metabolic pathways.

PMID- 16955211
TI  - Circulating ghrelin concentrations are lowered by intracerebroventricular
      insulin.
AB  - AIMS/HYPOTHESIS: Ghrelin is a peptide that is mainly produced by the stomach and
      stimulates food intake, adiposity and weight gain. Previous studies have
      documented that plasma levels of ghrelin are reduced by insulin, but the
      mechanisms that mediate this effect are unclear. METHODS: To determine whether
      phosphatidylinositol 3-kinase (PI(3)K) and/or mitogen-activated protein kinase
      (MAPK) are involved in this insulin action, we tested the intracerebroventricular
      (i.c.v.) effect of specific inhibitors of PI(3)K (LY294002 and wortmannin) and
      MAPK (PD98059 and UO126) on the insulin-mediated reduction of ghrelin levels in
      rats. RESULTS: Intracerebroventricular treatment with insulin reduced ghrelin
      levels. Inhibition of PI(3)K specifically blocked the insulin-induced reduction
      in ghrelin concentration, whereas inhibition of MAPK had no effect on insulin
      mediated actions. Moreover, pretreatment with i.c.v. PI(3)K inhibitors blocked
      the reduction of ghrelin levels after OGTT-induced hyperglycaemia and
      hyperinsulinaemia. CONCLUSIONS/INTERPRETATION: These data demonstrate that
      changes in insulin action in the central nervous system regulate circulating
      ghrelin levels and that PI(3)K is a specific mediator of this action.

PMID- 16955212
TI  - Altered cerebral regulation in type 2 diabetic patients with cardiac autonomic
      neuropathy.
AB  - AIMS/HYPOTHESIS: Assessment of cerebral regulation in diabetic patients is often
      problematic because of the presence of cardiac autonomic neuropathy. We evaluated
      the technique of oscillatory neck suction at 0.1 Hz to quantify cerebral
      regulation in diabetic patients and healthy control subjects. SUBJECTS AND
      METHODS: In nine type 2 diabetic patients with cardiac autonomic neuropathy and
      11 age-matched controls, we measured blood pressure and cerebral blood flow
      velocity responses to application of 0.1 Hz neck suction. We determined spectral
      powers and calculated the transfer function gain and phase shift between 0.1 Hz
      blood pressure and cerebral blood flow velocity oscillations as parameters of
      cerebral regulation. RESULTS: In the patients and control subjects, neck suction
      did not significantly influence mean values of the RR interval, blood pressure
      and cerebral blood flow velocity. The powers of 0.1 Hz blood pressure and
      cerebral blood flow velocity oscillations increased in the control subjects, but
      remained stable in the patients. Transfer function gain remained stable in both
      groups. Phase shift decreased in the patients, but remained stable in control
      subjects. CONCLUSIONS/INTERPRETATION: The absence of an increase in the power of
      0.1 Hz blood pressure and cerebral blood flow velocity oscillations confirmed
      autonomic neuropathy in the diabetic patients. Gain analysis did not show altered
      cerebral regulation. The decrease in phase shift in the patients indicates a more
      passive transmission of neck suction-induced blood pressure fluctuations onto the
      cerebrovascular circulation, i.e. altered cerebral regulation, in the patients,
      and is therefore suited to identifying subtle impairment of cerebral regulation
      in these patients.

PMID- 16955214
TI  - Clusterin/Apolipoprotein J up-regulation after zinc exposure, replicative
      senescence or differentiation of human haematopoietic cells.
AB  - Clusterin/Apolipoprotein J (CLU) is a cellular senescence biomarker implicated in
      several physiological processes. In this work we have investigated CLU expression
      and function in human haematopoietic cells. We found that early passage human T
      cell clones (TCC) express minimal endogenous amounts of CLU, which are
      significantly elevated in late passage cells. Moreover, exposure of TCC to
      increased levels of the essential micronutrient zinc in culture resulted in
      intense induction of CLU. Because haematopoietic cells cease proliferation
      following induction of terminal differentiation, we also studied the expression
      profile of CLU in the leukemic progenitor cell lines K562 and HL-60. We found
      that, like TCC, both cell lines express minimal endogenous levels of CLU in their
      actively proliferating state. However, when induced to differentiate into their
      distinct cell types, CLU was found to be up-regulated specifically in those cells
      expressing the main differentiation markers. Enforced stable over-expression of
      CLU in K562 cells inhibited the expression of the CD14 differentiation marker and
      blocked differentiation to either monocytes/megacaryoblasts or to erythrocytes.
      Overall, our results suggest that CLU is actively involved in both replicative
      senescence and terminal differentiation in different types of human
      haematopoietic cells.

PMID- 16955213
TI  - Advanced glycation end-products and methionine sulphoxide in skin collagen of
      patients with type 1 diabetes.
AB  - AIMS/HYPOTHESIS: We determined whether oxidative damage in collagen is increased
      in (1) patients with diabetes; (2) patients with diabetic complications; and (3)
      subjects from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of
      Diabetes Interventions and Complications (EDIC) study, with comparison of
      subjects from the former standard vs intensive treatment groups 4 years after
      DCCT completion. SUBJECTS, MATERIALS AND METHODS: We quantified the early
      glycation product fructose-lysine, the two AGEs N (epsilon)-(carboxymethyl)lysine
      (CML) and pentosidine, and the oxidised amino acid methionine sulphoxide (MetSO)
      in skin collagen from 96 patients with type 1 diabetes (taken from three groups:
      DCCT/EDIC patients and clinic patients from South Carolina and Scotland) and from
      78 healthy subjects. RESULTS: Fructose-lysine was increased in diabetic patients
      (p<0.0001), both with or without complications (p<0.0001). Controlling for
      HbA(1c), rates of accumulation of AGEs were higher in diabetic patients than
      control subjects, regardless of whether the former had complications (CML and
      pentosidine given as log(e)[pentosidine]) or not (CML only) (all p<0.0001). MetSO
      (log(e)[MetSO]) also accumulated more rapidly in diabetic patients with
      complications than in controls (p<0.0001), but rates were similar in patients
      without complications and controls. For all three products, rates of accumulation
      with age were significantly higher in diabetic patients with complications than
      in those without (all p<0.0001). At 4 years after the end of the DCCT, no
      differences were found between the previous DCCT management groups for fructose
      lysine, AGEs or MetSO. CONCLUSIONS/INTERPRETATION: The findings suggest that in
      type 1 diabetic patients enhanced oxidative damage to collagen is associated with
      the presence of vascular complications.

PMID- 16955215
TI  - Polymorphisms in MT1a gene coding region are associated with longevity in Italian
      Central female population.
AB  - Metallothioneins (MTs) play a pivotal role in zinc-related cell homeostasis
      because of their high affinity for zinc, which is in turn fundamental for immune
      response and antioxidant activity. MTs regulate zinc homeostasis by binding zinc
      and releasing zinc at the occurrence for immune response. The zinc release by MT
      is very limited in chronic inflammation and ageing. Some polymorphisms of MTs
      gene, in particular MT1a sub-isoform, may affect this release that is a problem
      still unresolved in ageing. The screening in the present paper of two
      polymorphisms in MT1a gene has revealed for the first time that the polymorphism
      corresponding to a A/C (Asp/Thr) transition at 647 nt position in the Mt1a coding
      region is the more involved in the longevity, at least in old women, rather than
      the other corresponding to A/G (Lys/Arg) transition at 1,245 nt position.
      Concomitantly, for the +647 MT1a polymorphism, old and very old female with
      Asp/Asp genotype (called C-carriers) display higher zinc release by MT (detected
      by Zinpyr-1 fluorescent probe in presence of NO donor), low MT levels and reduced
      IL-6 plasma concentrations, suggesting its involvement in longevity and in lower
      inflammatory status. This fact is confirmed by the analysis of haplotypes in
      which the allele Asp is more involved in longevity. Therefore the +647 MT1a
      polymorphism more affects MTs induction and zinc release, which are indispensable
      to undertake the inflammatory status under control and subsequently to reach
      healthy longevity.

PMID- 16955216
TI  - Telomerase activity in HeLa cervical carcinoma cell line proliferation.
AB  - Normal human somatic cells in culture have a limited dividing potential. This is
      due to DNA end replication problem, whereby telomeres shorten with each
      subsequent cell division. When a critical telomere length is reached cells enter
      senescence. To overcome this problem, immortal HeLa cell line express telomerase,
      an enzyme that prevents telomere shortening. Although immortal, the existence of
      non-dividing cells that do not incorporate (3)H-thymidine over 24 h of growth has
      been well documented in this cell line. Using DiI labeling and high-speed cell
      sorting, we have separated and analyzed fractions of HeLa cells that divided
      vigorously as well as those that cease divisions over several days in culture. We
      also analyzed telomerase activity in separated fractions and surprisingly, found
      that the fraction of cells that divided 0-1 time over 6 days in culture have
      several times higher endogenous telomerase activity than the fastest dividing
      fraction. Additionally, the non-growing fraction regains an overall high labeling
      index and low SA-beta-Gal activity when subcultured again. This phenomenon should
      be considered if telomerase inhibition is to be used as an approach to cancer
      therapy. In this paper we also discuss possible molecular mechanisms that
      underlie the observed results.

PMID- 16955217
TI  - Association of the F352V variant of the Klotho gene with bone mineral density.
AB  - Klotho gene codes for a protein with glucuronidase activity and is thought to
      influence bone and vascular homeostasis. We studied the relationship of a common
      T/G polymorphism, resulting in a phenylalanine (F) to valine (V) substitution at
      aminoacid position 352, with bone mineral density (BMD) and osteoporotic
      fractures. The study group comprised 914 Spanish women, including 438 control
      subjects, 190 patients with osteoporosis, 198 with hip fractures, and 88 patients
      with severe osteoarthritis. BMD was measured by DEXA in 540 women from the
      control and osteoporosis groups. Allele frequencies were 86% and 14%, for the F
      and V alleles, respectively. In comparison with the most common FF genotype,
      postmenopausal women with FV/VV genotypes had higher hip BMD (femoral neck: 0.673
      +/- 0.011 vs. 0.644 +/- 0.006 g/cm(2); P = 0.02; total hip: 0.807 +/- 0.014 vs.
      0.774 +/- 0.008 g/cm(2); P = 0.03). Klotho alleles explained about 1.5% of BMD
      variance, but were not associated to the risk of osteoporotic spine or hip
      fractures. The Klotho genotype was not associated to BMD in premenopausal women.
      In conclusion, the F352V Klotho polymorphism is associated with BMD in
      postmenopausal women, suggesting that Klotho gene variants influence skeletal
      aging.

PMID- 16955218
TI  - Changes of brain activity in the aged SAMP mouse.
AB  - This study investigates characteristics of aging in the central nervous system of
      the senescence accelerated prone mice (SAMP8). We examined 3 and 10-months old
      senescence-accelerated-prone mice (SAMP8) for functional and molecular changes in
      their brains, specifically in the hippocampus and somatosensory cortex. There was
      no statistically significant increase in the apoptosis indicators as revealed by
      Western Blotting for BAD and TUNEL experiments. However, the functional magnetic
      resonance imaging showed an increase in the area of BOLD images from the 3-month
      old to the 10-months old SAMP mice upon the application of tail stimulus. These
      results demonstrated a lack of neuronal deaths but an increase in the activated
      brain area with age.

PMID- 16955219
TI  - Evaluation of molecular genetic alterations associated with tumor progression in
      a case of gliomatosis cerebri.
AB  - Gliomatosis cerebri (GC) is a rare tumor characterized by widespread infiltration
      of the brain and spinal cord. Although GC usually demonstrates histomorphological
      features of a low-grade tumor, the formation of secondary highly malignant tumor
      regions may occur. In order to reveal molecular genetic changes associated with
      tumor progression in GC, we analyzed factors known to be associated with
      malignant progression in common astocytomas in an unusual GC case of an 18-year
      old patient suffering from this disease for almost 7 years. We detected allelic
      losses in the Rb gene and in exon 4 of the TP53 gene in a tumor region
      corresponding to a glioblastoma multiforme. EGFR or MDM2 gene amplifications were
      absent, and no PTEN mutation or allelic loss on chromosome 10 could be detected.
      Moreover, compared to tumor-free brain tissue of this patient, tumor regions
      showed increased EGFR expression. These findings show that malignant progression
      in GC might be associated with the acquisition of molecular genetic changes also
      found in low-grade astrocytomas with progression to secondary glioblastoma. These
      data support the notion that GC can be regarded as a subtype of a common
      astrocytoma.

PMID- 16955220
TI  - Growth inhibition and induction of apoptosis and differentiation of tanshinone
      IIA in human glioma cells.
AB  - Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Danshen, a
      widely used Chinese herbal medicine. It has antioxidant properties, cytotoxic
      activities against multiple human cancer cells, inducing apoptosis and
      differentiation of some human cancer cells. The purpose of this study is to
      confirm its anticancer activity on human glioma cells, and to elucidate mechanism
      of its activity. Human glioma cells were tested in vitro for cytotoxicity, colony
      formation inhibition, BrdU incorporation after treatment with tanshinone IIA. Its
      effect of apoptosis induction was detected through EB/AO staining, cell cycle
      analysis and the expressions of ADPRTL1 and CYP1A1 genes, the differentiation
      induction effect was investigated through morphology, mRNA and protein
      expressions of GFAP and nestin genes by RT-PCR and immunocytochemistry.
      Tanshinone IIA demonstrated a dose- and time-dependent inhibitory effect on cell
      growth, IC(50) was 100 ng/ml, and it significantly inhibited colony formation and
      BrdU incorporation of human glioma cells. After treatment with 25-100 ng/ml of
      tanshinone IIA, the apoptotic cells increased significantly (P < 0.01), the cells
      in G(0)/G(1) phase increased (P < 0.01), and decreased in S phase, ADPRTL1 and
      CYP1A1 mRNA expression increased 1-2 folds. The cells treated with 100 ng/ml
      tanshinone IIA demonstrated astrocytes or neuron-like morphology, GFAP mRNA and
      protein expressions increased, nestin mRNA and protein expressions decreased
      significantly. The findings in this study suggested that tanshinone IIA exhibited
      strong effects on growth inhibition and induction of apoptosis and
      differentiation in human glioma cells. It might serve as a novel promising
      differentiation-inducing and/or therapeutic agent for human gliomas, and need to
      be investigated further.

PMID- 16955221
TI  - Human glioblastoma biopsy spheroids xenografted into the nude rat brain show
      growth inhibition after stereotactic radiosurgery.
AB  - BACKGROUND: The Gamma Knife is currently used to boost treatment of malignant
      gliomas. However, few experimental studies have focused on its radiobiological
      effects. In this work, the growth and invasiveness of human glioblastoma
      spheroids xenografted into nude rat brains were assessed after radiosurgery.
      Temporary in vitro as well as long-term in vivo radiation effects were studied.
      METHODS: Glioblastoma biopsy spheroids were irradiated with 12 or 24 Gy. Short
      term in vitro spheroid viability and tumour cell migration was determined by
      microscopic techniques. Pre-irradiated glioblastoma spheroids were implanted into
      brains of immunosuppressed rats. Long-term tumour development was assessed by
      magnetic resonance (MR) imaging, and animal survival was recorded. An
      immunohistochemical analysis was performed on the sectioned rat brains. RESULTS:
      Both un-irradiated and irradiated spheroids remained viable during 2 months in
      culture, but a dose-dependent inhibition of tumour growth and migration was seen.
      MR imaging 4 weeks after implantation also showed a dose-dependent inhibition in
      tumour development. Median animal survival times were 25.5 days (control group),
      43 days (12 Gy group) and 96 days (24 Gy group). The study of in vivo long-term
      radiation effects on the remaining viable tumour population showed no difference
      in Ki-67 labelling index and microvascular density before and after radiosurgery.
      CONCLUSIONS: A dose-dependent inhibition of tumour growth and invasion, as well
      as a dose-dependent increase in animal survival was observed. The model system
      described is well suited for assessing the radiobiological effects of Gamma Knife
      radiosurgery. The results indicate that radiosurgery of malignant gliomas might
      be effective in controlling tumour progression in selected glioblastoma patients.

PMID- 16955222
TI  - Metastatic atypical choroid plexus papilloma: a case report.
AB  - Choroid plexus papillomas (CPPs) are rare adult tumours and metastatic disease is
      even less common, more typically associated with choroid plexus carcinoma. We
      present the case of a 32-year-old patient with multiple metastases arising along
      the length of the neuraxis 3 years after resection of an atypical fourth
      ventricular CPP. Metastatic deposits were found from the mid-brain to the lumbar
      cistern and the patient underwent repeat excision of the fourth ventricular
      tumour, partial resection of a cervico-thoracic deposit and craniospinal
      radiotherapy. Possible explanations for the rarity of atypical CPP include
      unclear diagnostic criteria leading to under-representation in reported cases. We
      review the current literature on metastatic CPP and discuss the role of surgery
      and adjuvant therapy in relation to both typical and atypical disease.

PMID- 16955223
TI  - Clear cell meningioma, an uncommon variant of meningioma: a clinicopathologic
      study of nine cases.
AB  - AIMS: Clear cell meningioma (CCM) is an uncommon variant of meningioma, which
      affect younger patients, occur more often in spinal or cerebello pontine
      locations and shows a higher recurrence rate. Only few case reports have been
      described in the literature. The study has been undertaken to document the
      clinicopathological features of nine cases of CCM, operated at All India
      Institute of Medical Sciences during 1998 to December 2005. METHODS: Clinical
      information was retrieved from the records of our Neurosurgery Department. The
      cases were stained with H&E, periodic Acid Schiff (PAS) with and without
      diastase. Immunohistochemistry for pancytokeratin, epithelial membrane antigen,
      vimentin, glial fibrillary acidic protein, and MIB-1 was done in all cases.
      RESULTS: During a period of 8 years, nine cases of CCM were diagnosed. Age ranged
      from 10 to 65 years (median age 26.0 years) with female predominance. Most common
      location was posterior fossa (CP angle). Clinically most of the patients
      presented with history of headache and features of cranial nerve palsies. The
      duration of symptoms varied from 3 to 60 months (mean 16.7 and median of 4
      months). Radiologically lesions showed homogenous enhancement and were isointense
      to brain parenchyma. Histopathologic examination revealed tumor cells to be
      arranged in sheets with clear cytoplasm and monomorphic nuclei. MIB-1 labeling
      index (LI) ranged from 2 to 12% with a mean of 9%. Follow up varied from 3 to 84
      months (median 36 months) and recurrence was noted in two patients after 2 and 3
      years of surgery, respectively, despite their low MIB-1 labeling indices.
      CONCLUSIONS: CCM is a rare variant of meningioma with poor outcome. Less than 50
      cases have been described in the literature. Low rate of recurrence and
      recurrence despite their low MIB-1 LI are some of the features, which needs to be
      documented. Hence, larger number of cases with adequate follow-up data need to be
      studied further to establish the clinical significance of this variant.

PMID- 16955224
TI  - Tbx3, a transcriptional factor, involves in proliferation and osteogenic
      differentiation of human adipose stromal cells.
AB  - Tbx3 is a transcription factor, the mutation of which causes ulnar mammary
      syndrome (UMS) characterized by abnormality and hypoplasia of the mammary gland,
      teeth, limbs, hair and genitalia. Tbx3 has been reported to be related to
      apoptosis and proliferation of rat bladder carcinoma cell and to regulate
      proliferation and differentiation of mouse osteoblast cells. Human adipose tissue
      stromal cells (hADSC) have been defined as multipotential adult stem cells,
      capable of differentiating into a variety of cell types such as osteoblasts,
      chondrocytes, adipocytes, muscle cells, and neural cells. To determine the
      functional roles of Tbx3 expression in hADSC, we used lentivirus siRNA vector.
      Expression of Tbx3 was downregulated during culture expansion. Downregulation of
      Tbx3 in hADSC by transduction of siTbx3 lentivirus decreased proliferation and
      osteogenic differentiation of hADSC. Expression of Tbx3 and the ratio of Tbx3 +
      2a to Tbx3 increased during osteogenic differentiation. This report shows that
      Tbx3 plays an important role on osteogenic differentiation and proliferation of
      human mesenchymal stem cell derived from adipose tissue.

PMID- 16955225
TI  - Impact of lactate in the perfusate on function and metabolic parameters of
      isolated working rat heart.
AB  - The goal of this study was to investigate the effect of 1 mM exogenous lactate on
      cardiac function, and some metabolic parameters, such as glycolysis, glucose
      oxidation, lactate oxidation, and fatty acid oxidation, in isolated working rat
      hearts. Hearts from male Sprague-Dawley rats were isolated and perfused with 5 mM
      glucose, 1.2 mM palmitate, and 100 microU/ml insulin with or without 1 mM
      lactate. The rates of glycolysis, glucose, lactate, and fatty acid oxidation were
      determined by supplementing the buffer with radiolabeled substrates. Cardiac
      function was similar between lactate+ and lactate- hearts. Glycolysis was not
      affected by 1 mM lactate. The addition of lactate did not alter glucose oxidation
      rates. Interestingly, palmitate oxidation rates almost doubled when 1 mM lactate
      was present in the perfusate. This study suggests that subst rate supply to the
      heart is crucially important when evaluating the data from metabolic studies.

PMID- 16955226
TI  - Hydrogen peroxide increases the phagocytic function of human neutrophils by
      calcium mobilisation.
AB  - We have studied the effect of exogenous administration of hydrogen peroxide
      (H(2)O(2)) on phagocytic activity of human neutrophils. The treatment of cells
      with increasing concentrations of H(2)O(2) evoke a significant elevation of
      phagocytic function assayed as phagocytic index, percentage and efficiency; and
      was similar to that induced by the calcium mobilising agonist formyl-methionyl
      leucyl-phenylalanine (fMLP). This stimulatory effect was reduced by pre-treatment
      of neutrophils with catalase and abolished in neutrophils loaded with the
      intracellular calcium quelator dimethyl BAPTA. In the absence of extracellular
      calcium, treatment of cells with H(2)O(2) resulted in a increase in [Ca(2+)]( i
      ), indicating the release of calcium from intracellular stores. H(2)O(2)
      abolished the typical calcium release stimulated by the physiological agonist
      fMLP, while depletion of agonist-sensitive calcium pools by fMLP was able to
      prevent H(2)O(2)-induced calcium release. We conclude that H(2)O(2) induces
      calcium release from agonist-sensitive stores and consequently increase the
      phagocytosis process.

PMID- 16955227
TI  - Central neurocytoma with unusually high MIB-1 index.

PMID- 16955228
TI  - Blood amino acids concentration during insulin induced hypoglycemia in rats: the
      role of alanine and glutamine in glucose recovery.
AB  - Our purpose was to determine the blood amino acid concentration during insulin
      induced hypoglycemia (IIH) and examine if the administration of alanine or
      glutamine could help glycemia recovery in fasted rats. IIH was obtained by an
      intraperitoneal injection of regular insulin (1.0 U/kg). The blood levels of the
      majority of amino acids, including alanine and glutamine were decreased (P <
      0.05) during IIH and this change correlates well with the duration than the
      intensity of hypoglycemia. On the other hand, the oral and intraperitoneal
      administration of alanine (100 mg/kg) or glutamine (100 mg/kg) accelerates
      glucose recovery. This effect was partly at least consequence of the increased
      capacity of the livers from IIH group to produce glucose from alanine and
      glutamine. It was concluded that the blood amino acids availability during IIH,
      particularly alanine and glutamine, play a pivotal role in recovery from
      hypoglycemia.

PMID- 16955229
TI  - Taurine increases mitochondrial buffering of calcium: role in neuroprotection.
AB  - We have determined the role of mitochondria in the sequestration of calcium after
      stimulation of cerebellar granule cells with glutamate. In addition we have
      evaluated the neuroprotective role of taurine in excitotoxic cell death.
      Mitochondrial inhibitors were used to determine the calcium buffering capacity of
      mitochondria, as well as how taurine regulates the ability of mitochondria to
      buffer intracellular calcium during glutamate depolarization and excitotoxicity.
      We report here that pre-treatment of cerebellar granule cells with taurine (1 mM,
      24 h) significantly counteracted glutamate excitotoxicity. The neuroprotective
      role of taurine was mediated through regulation of cytoplasmic free calcium
      ([Ca(2+)]( i )), and intra-mitochondrial calcium homeostasis, as determined by
      fluo-3 and (45)Ca(2+)-uptake. Furthermore, the overall mitochondrial function was
      increased in the presence of taurine, as assessed by rhodamine accumulation into
      mitochondria and total cellular ATP levels. We specifically tested the hypothesis
      that taurine reduces glutamate excitotoxicity through both the enhancement of
      mitochondrial function and the regulation of intracellular (cytoplasmic and intra
      mitochondrial) calcium homeostasis. The role of taurine in modulating
      mitochondrial calcium homeostasis could be of particular importance under
      pathological conditions that are characterized by excessive calcium overloads.
      Taurine may serve as an endogenous neuroprotective molecule against brain
      insults.

PMID- 16955230
TI  - A locus for familial skewed X chromosome inactivation maps to chromosome Xq25 in
      a family with a female manifesting Lowe syndrome.
AB  - In mammals, X-linked gene products can be dosage compensated between males and
      females by inactivation of one of the two X chromosomes in the developing female
      embryos. X inactivation choice is usually random in embryo mammals, but several
      mechanisms can influence the choice determining skewed X inactivation. As a
      consequence, females heterozygous for X-linked recessive disease can manifest the
      full phenotype. Herein, we report a family with extremely skewed X inactivation
      that produced the full phenotype of Lowe syndrome, a recessive X-linked disease,
      in a female. The X chromosome inactivation studies detected an extremely skewed
      inactivation pattern with a ratio of 100:0 in the propositus as well as in five
      out of seven unaffected female relatives in four generations. The OCRL1 "de novo"
      mutation resides in the active paternally inherited X chromosome. X chromosome
      haplotype analysis suggests the presence of a locus for the familial skewed X
      inactivation in chromosome Xq25 most likely controlling X chromosome choice in X
      inactivation or cell proliferation. The description of this case adds Lowe
      syndrome to the list of X-linked disorders which may manifest the full phenotype
      in females because of the skewed X inactivation.

PMID- 16955231
TI  - Perceived conflicts between pastoralism and conservation of the kiang Equus kiang
      in the Ladakh Trans-Himalaya, India.
AB  - An emerging conflict with Trans-Himalayan pastoral communities in Ladakh's
      Changthang Plateau threatens the conservation prospects of the kiang (Equus
      kiang) in India. It is locally believed that Changthang's rangelands are
      overstocked with kiang, resulting in forage competition with livestock. Here, we
      provide a review and preliminary data on the causes of this conflict. Erosion of
      people's tolerance of the kiang can be attributed to factors such as the loss of
      traditional pastures during an Indo-Chinese war fought in 1962, immigration of
      refugees from Tibet, doubling of the livestock population in about 20 years, and
      increasing commercialization of cashmere (pashmina) production. The perception of
      kiang overstocking appears misplaced, because our range-wide density estimate of
      0.24 kiang km(-2) (+/- 0.44, 95% CL) is comparable to kiang densities reported
      from Tibet. A catastrophic decline during the war and subsequent recovery of the
      kiang population apparently led to the overstocking perception in Ladakh. In the
      Hanle Valley, an important area for the kiang, its density was higher (0.56 km(
      2)) although even here, we estimated the total forage consumed by kiang to be
      only 3-4% compared to 96-97% consumed by the large livestock population (78 km(
      2)). Our analysis nevertheless suggests that at a localized scale, some herders
      do face serious forage competition from kiang in key areas such as moist sedge
      meadows, and thus management strategies also need to be devised at this scale. In
      depth socioeconomic surveys are needed to understand the full extent of the
      conflicts, and herder-centered participatory resolution needs to be facilitated
      to ensure that a sustainable solution for livelihoods and kiang conservation is
      achieved.

PMID- 16955233
TI  - Multiscale drivers of water chemistry of boreal lakes and streams.
AB  - The variability in surface water chemistry within and between aquatic ecosystems
      is regulated by many factors operating at several spatial and temporal scales.
      The importance of geographic, regional-, and local-scale factors as drivers of
      the natural variability of three water chemistry variables representing buffering
      capacity and the importance of weathering (acid neutralizing capacity, ANC),
      nutrient concentration (total phosphorus, TP), and importance of allochthonous
      inputs (total organic carbon, TOC) were studied in boreal streams and lakes using
      a method of variance decomposition. Partial redundancy analysis (pRDA) of ANC,
      TP, and TOC and 38 environmental variables in 361 lakes and 390 streams showed
      the importance of the interaction between geographic position and regional-scale
      variables. Geographic position and regional-scale factors combined explained
      15.3% (streams) and 10.6% (lakes) of the variation in ANC, TP, and TOC. The
      unique variance explained by geographic, regional, and local-scale variables
      alone was <10%. The largest amount of variance was explained by the pure effect
      of regional-scale variables (9.9% for streams and 7.8% for lakes), followed by
      local-scale variables (2.9% and 5.8%) and geographic position (1.8% and 3.7%).
      The combined effect of geographic position, regional-, and local-scale variables
      accounted for between 30.3% (lakes) and 39.9% (streams) of the variance in
      surface water chemistry. These findings lend support to the conjecture that lakes
      and streams are intimately linked to their catchments and have important
      implications regarding conservation and restoration (management) endeavors.

PMID- 16955232
TI  - Expert stakeholders' views on the management of human pharmaceuticals in the
      environment.
AB  - Human pharmaceuticals are ubiquitous water contaminants that may have subtle
      detrimental effects on aquatic organisms, and possibly also on human health. The
      risks of pharmaceuticals, or pharmaceutically active compounds, remain poorly
      understood. Awareness of the presence of pharmaceuticals in the environment,
      coupled with evidence of effects such as fish feminization, however, suggest that
      precautionary management action to reduce the release of pharmaceuticals to the
      environment should be considered. The purpose of our study was to evaluate the
      scope of the issue and possible management strategies from the perspectives of
      expert stakeholders, drawn from government, academia, and the pharmaceutical and
      consulting industries, involved in scientific research or policy and management
      activity, from Canada, the United States, and Europe. Twenty-seven interviewees
      were asked about their views on management strategies such as pharmaceutical
      return programs and incentives for the development of "green" pharmaceuticals.
      Interviewees generally believed that pharmaceuticals in the environment
      represented a concern for both human and ecosystem health, although they were
      more concerned about impacts on aquatic ecosystems. They believed that advanced
      wastewater treatment technology, education of medical professionals to reduce
      overprescription, pharmaceutical-return programs coupled with public education,
      and requirements for all municipalities to have a minimum of secondary wastewater
      treatment were the most effective management strategies to reduce the
      environmental impacts of pharmaceuticals. These strategies should be considered
      by governments interested in managing the risks of human pharmaceuticals in the
      environment. Combinations of management strategies will likely be most effective
      in mitigating the risks presented by pharmaceuticals.

PMID- 16955234
TI  - Interaction between the environment and animals in urban settings: integrated and
      participatory planning.
AB  - In urban ecosystems, the ecological system has become completely unbalanced;
      this, in turn, has led to an increase in well-known problems such as air
      pollution, ground pollution, and water pollution. This imbalance has also led to
      the growth and spread of pathogens harmful to man, animals, and plants. Urban
      sustainability indicators, both global and local, also "indicate" the percentage
      of population, but these refer only to the human population, not the animal
      population. Cities need good waste, water, and air management, effective traffic
      planning, and good zoning of businesses, crafts, and services; over and above
      these activities, cities also need for planning to take into account the
      existence of pets (dogs, cats, and etc.) and nonpet animals (insects, birds,
      mice, etc.). Cities tend to be designed around humans and "on a human scale,"
      without taking into account the fact that a huge animal population is living side
      by side with people. That explains why overcrowding tends to go hand in hand with
      urbanization; all these populations, including humans, need to adapt to new
      spaces and often need to drastically change their behavior. This is a fact that
      must be included when drafting sustainable city plans. The supposed strategy is
      that of "integrated-participatory" control of the interactions between the
      environment and animals in the cities. Strategy will focus on the development of
      integrated approaches and tools for environment and animal management in the
      context of urban settings. This will require such specific methods as ecological
      balance sheets and ecoplans for the planning, management, and control of the
      interrelation among environment, animal, and public health. The objective is to
      develop a better understanding of urban biodiversity and of urban ecosystem
      functioning, in order to understand and minimize the negative impacts of human
      activities on them. The research will focus on assessing and forecasting changes
      in urban biodiversity, structure, function, and dynamics of urban ecosystems,
      with relationships among society, economy, biodiversity, and habitats.

PMID- 16955235
TI  - Inference from proteobacterial operons shows piecewise organization: a reply to
      Price et al.

PMID- 16955236
TI  - Horizontal gene transfer in aminoacyl-tRNA synthetases including leucine-specific
      subtypes.
AB  - Aminoacyl-tRNA synthetases catalyze a fundamental reaction for the flow of
      genetic information from RNA to protein. Their presence in all organisms known
      today highlights their important role in the early evolution of life. We
      investigated the evolutionary history of aminoacyl-tRNA synthetases on the basis
      of sequence data from more than 200 Archaea, Bacteria, and Eukaryota.
      Phylogenetic profiles are in agreement with previous observations that many genes
      for aminoacyl-tRNA synthetases were transferred horizontally between species from
      all domains of life. We extended these findings by a detailed analysis of the
      history of leucyl-tRNA synthetases. Thereby, we identified a previously
      undetected case of horizontal gene transfer from Bacteria to Archaea based on
      phylogenetic profiles, trees, and networks. This means that, finally, the last
      subfamily of aminoacyl-tRNA synthetases has lost its exceptional position as the
      sole subfamily that is devoid of horizontal gene transfer. Furthermore, the
      leucyl-tRNA synthetase phylogenetic tree suggests a dichotomy of the
      archaeal/eukaryotic-cytosolic and bacterial/eukaryotic-mitochondrial proteins. We
      argue that the traditional division of life into Prokaryota (non-chimeric) and
      Eukaryota (chimeric) is favorable compared to Woese's trichotomy into
      Archaea/Bacteria/Eukaryota.

PMID- 16955237
TI  - Mammalian male mutation bias: impacts of generation time and regional variation
      in substitution rates.
AB  - In mammals, males undergo a greater number of germline cell divisions compared
      with females. Thus, the male germline accumulates more DNA replication errors,
      which result in male mutation bias-a higher mutation rate for males than for
      females. The phenomenon of male mutation bias has been investigated mostly for
      rodents and primates, however, it has not been studied in detail for other
      mammalian orders. Here we sequenced and analyzed five introns of three genes
      (DBX/DBY, UTX/UTY, and ZFX/ZFY) homologous between X and Y chromosomes in several
      species of perissodactyls (horses and rhinos) and of primates. Male mutation bias
      was evident: substitution rate was higher for a Y chromosome intron than for its
      X chromosome homologue for all five intron pairs studied. Substitution rates
      varied regionally among introns sequenced on the same chromosome and this
      variation influenced male mutation bias inferred from each intron pair.
      Interestingly, we observed a positive correlation in substitution rates between
      homologous X and homologous Y introns as well as between orthologous primate and
      perissodactyl introns. The male-to-female mutation rate ratio estimated from
      concatenated sequences of five perissodactyl introns was 3.88 (95% CI = 2.90
      6.07). Using the data generated here and estimates available in the literature,
      we compared male mutation bias among several mammalian orders. We conclude that
      male mutation bias is significantly higher for organisms with long generation
      times (primates, perissodactyls, and felids) than for organisms with short
      generation times (e.g., rodents) since the former undergo a greater number of
      male germline cell divisions.

PMID- 16955238
TI  - The distribution of L1 and Alu retroelements in relation to GC content on human
      sex chromosomes is consistent with the ectopic recombination model.
AB  - The distribution of Alu and L1 retroelements in the human genome changes with
      their age. Active retroelements target AT-rich regions, but their frequency
      increases in GC- and gene-rich regions of the genome with increasing age of the
      insertions. Currently there is no consensus on the mechanism generating this
      pattern. In this paper we test the hypothesis that selection against deleterious
      deletions caused by ectopic recombination between repeats is the main cause of
      the inhomogeneous distribution of L1s and Alus, by means of a detailed analysis
      of the GC distribution of the repeats on the sex chromosomes. We show that (1)
      unlike on the autosomes and X chromosome, L1s do not accumulate on the Y
      chromosome in GC-rich regions, whereas Alus accumulate there to a minor extent;
      (2) on the Y chromosome Alu and L1 densities are positively correlated, unlike
      the negative correlation on other chromosomes; and (3) in gene-poor regions of
      chromosome 4 and X, the distribution of Alus and L1s does not shift toward GC
      rich regions. In addition, we show that although local GC content of long L1
      insertions is lower than average, their selective loss from recombining
      chromosomes is not the main cause of the enrichment of ancient L1s in GC-rich
      regions. The results support the hypothesis that ectopic recombination causes the
      shift of Alu and L1 distributions toward the gene-rich regions of the genome.

PMID- 16955240
TI  - YKL-40, a new inflammatory marker with relation to insulin resistance and with a
      role in endothelial dysfunction and atherosclerosis.
AB  - Substantial evidence supports a role of chronic subclinical inflammation and
      activation of the innate immune system in the pathogenesis of insulin resistance
      and endothelial dysfunction and the development of type 2 diabetes (T2D) and
      atherosclerosis. Several proinflammatory cytokines, acute phase-reactants and
      cell adhesion molecules play a pivotal role in this chronic subclinical
      inflammation but a comprehensive understanding of the interrelations of these
      molecules is still needed. YKL-40 is a new inflammatory marker with relation to
      acute and chronic inflammation as well as cancer. It is secreted in vitro from a
      variety of human cells, including vascular smooth muscle cells (VSMCs), activated
      macrophages and macrophages during late stages of differentiation and is found in
      vivo in subpopulations of macrophages in tissues with inflammation and
      extracellular tissue remodelling, such as macrophages in atherosclerotic plaques.
      YKL-40 promotes chemotaxis, cell attachment and migration of VSMCs and the
      formation of branching tubules suggesting that YKL-40 plays a role in
      angiogenesis. Latest studies reveal that YKL-40 is elevated in patients with T2D
      and is related to insulin resistance. This article reviews the studies of YKL-40
      with focus on a possible role of YKL-40 in insulin resistance, endothelial
      dysfunction and atherosclerosis.

PMID- 16955239
TI  - Nonneutral GC3 and retroelement codon mimicry in Phytophthora.
AB  - Phytophthora is a genus entirely comprised of destructive plant pathogens. It
      belongs to the Stramenopila, a unique branch of eukaryotes, phylogenetically
      distinct from plants, animals, or fungi. Phytophthora genes show a strong
      preference for usage of codons ending with G or C (high GC3). The presence of
      high GC3 in genes can be utilized to differentiate coding regions from noncoding
      regions in the genome. We found that both selective pressure and mutation bias
      drive codon bias in Phytophthora. Indicative for selection pressure is the higher
      GC3 value of highly expressed genes in different Phytophthora species. Lineage
      specific GC increase of noncoding regions is reminiscent of whole-genome mutation
      bias, whereas the elevated Phytophthora GC3 is primarily a result of translation
      efficiency-driven selection. Heterogeneous retrotransposons exist in Phytophthora
      genomes and many of them vary in their GC content. Interestingly, the most
      widespread groups of retroelements in Phytophthora show high GC3 and a codon bias
      that is similar to host genes. Apparently, selection pressure has been exerted on
      the retroelement's codon usage, and such mimicry of host codon bias might be
      beneficial for the propagation of retrotransposons.

PMID- 16955241
TI  - FK506 (tacrolimus) improves lung injury through inhibition of Fas-mediated
      inflammation.
AB  - OBJECTIVE: To investigate whether FK506 (tacrolimus) can inhibit Fas- or A23187
      induced interleukin (IL)-8 expression and cell death in A549 human alveolar
      epithelial cells, plus Fas-mediated acute lung injury in vivo. METHODS: Assays
      for IL-8, cell death, and caspase-3 activity were performed. A549 cells were
      treated with 25 micromol A23187 or 0.2 microg/ml agonistic anti-Fas antibody plus
      5 ng/ml interferon-gamma (IFN-gamma). Tacrolimus was treated at 0.1-10 ng/ml. For
      in vivo experiment, agonistic anti-Fas antibody (Jo2) at 2.5 microg/g was
      intratracheally instilled into C57BL/6 mice. Neutrophils and protein contents in
      bronchoalveolar lavage (BAL) fluid were measured within 24 h of instillation.
      Mice were orally treated with 32 mg/kg of tacrolimus 24 h and 1 h prior to
      instillation. RESULTS: Both Fas and A23187 caused significant IL-8 expression and
      cell death in A549 cells. Tacrolimus inhibited A23187-induced IL-8 expression
      alone while it protected all Fas-mediated responses. Mice instilled
      intratracheally with Jo2 at 2.5 microg/g had significant increases in
      neutrophils, protein contents in BAL fluid and in expression of chemoattractants
      for neutrophils. These increases were reversed by tacrolimus. CONCLUSIONS:
      Tacrolimus serves as a therapeutic option for improving lung injury through
      inhibition of Fas-mediated inflammation.

PMID- 16955242
TI  - The effect of substance P on nitric oxide release in a rheumatoid arthritis
      model.
AB  - OBJECTIVE: The inflammatory mediator substance P (SP) acts principally through
      the neurokinin (NK1) receptor. We assessed the influence of SP on production of
      NO and its possible role in the pathogenesis of rheumatoid arthritis (RA).
      METHODS: The effect of SP (0.1-100 nM) on concentrations of the NO metabolite,
      nitrite, produced by synovial fibroblasts from RA patients was studied. For
      comparison, the effects of TNF-alpha (0.57 pM-5.7 nM) and IL-1beta (0.57 pM-5.7
      nM) were also studied. In parallel studies, footpad inflammation was induced in
      NK1 receptor knock-out (KO) and wild-type (WT) mice, and swelling and NO
      metabolite levels were measured. RESULTS: In cultured synoviocytes, SP, TNF-alpha
      and IL-1beta induced significantly increased nitrite concentrations. Consistent
      with a role for NO in SP-mediated inflammatory reactions, the plasma NO
      metabolite level in WT mice was significantly increased at 3 days following an
      injection of 10 mg/ml Mycobacterium tuberculosis, but there was no significant
      change in NK1 KO mice. These results were paralleled by the changes in footpad
      swelling in WT mice compared to NK1 KO mice. CONCLUSION: SP, like TNF-alpha and
      IL-1beta, induces NO in both rheumatoid synoviocytes and experimental models of
      inflammation. Treatments directed against SP may have important and hitherto
      unrecognised anti-inflammatory effects.

PMID- 16955243
TI  - A comparison of levocetirizine and desloratadine in the histamine-induced wheal
      and flare response in human skin in vivo.
AB  - BACKGROUND: The histamine-induced wheal and flare response was used to compare
      quantitatively the antihistaminic potency of levocetirizine and desloratadine.
      METHODS: In this double-blind, placebo-controlled crossover study, 24 healthy
      male non-atopic volunteers received weekly single doses of 1.25, 2.5 or 5 mg
      levocetirizine, 2.5, 5 or 10 mg desloratadine, or placebo. Four hours after
      dosing, histamine (100 mg/ml) skin prick tests were performed on the volar
      surface of both forearms. The diameters of the wheals and flares were measured 10
      minutes later. Sedation was evaluated using a visual analogue scale and a
      motricity test. The effects of individual drug doses were compared using
      Student's t-test for paired data and the overall effects of the two drugs by
      ANOVA. RESULTS: All doses of levocetirizine significantly (P < 0.0001) inhibited
      both wheals and flares in a dose-related manner. Only the 10 mg dose of
      desloratadine achieved significant inhibition of response. ANOVA showed
      levocetirizine to be significantly (P < 0.0001) more active than desloratadine.
      Neither drug caused significant sedation or loss of motricity. CONCLUSION:
      Levocetirizine is significantly more effective than desloratadine in inhibiting
      wheal and flare responses to histamine in human skin in vivo, with 1.25 mg
      levocetirizine being more effective than 10 mg desloratadine.

PMID- 16955244
TI  - Role of nitric oxide in the local and systemic pathophysiological effects induced
      by Bothrops asper snake venom in mice.
AB  - OBJECTIVE: To assess the role of nitric oxide in the most relevant local and
      systemic manifestations in mice injected with the venom of the snake Bothrops
      asper. Mice were pretreated with nitric oxide synthase inhibitors, and the
      modifications of the pathological effects induced by the venom were tested.
      RESULTS: Inhibition of NO synthesis did not affect acute local myonecrosis and
      hemorrhage in muscle tissue upon intramuscular injection of venom. Local footpad
      edema was reduced in mice pretreated with the NO synthase inhibitor L-NAME, and a
      reduction in the extent of inflammatory infiltrate in muscle tissue was observed
      after envenomation in mice pretreated with L-NAME and aminoguanidine. The most
      pronounced effect of NOS inhibition by L-NAME was an increment in the lethal
      activity of the venom, when injected by the intraperitoneal route. CONCLUSION:
      Nitric oxide does not seem to play a significant role in the local acute
      pathological alterations (hemorrhage and myonecrosis) induced by B. asper venom
      in mice, although it contributes to edema and inflammatory infiltrate. Nitric
      oxide exerts a protective role in the systemic pathophysiological manifestations
      leading to lethality.

PMID- 16955245
TI  - Mechanism and function of heat shock-dependent IkappaBalpha expression.
AB  - OBJECTIVE: Heat shock is known to inhibit activation of the NF-kappa B pathway.
      One potential mechanism of this effect is de novo expression of the intracellular
      NF-kappaB inhibitor, Ikappa Balpha. Herein we sought to elucidate the mechanisms
      by which heat shock induces Ikappa Balpha gene expression and the functional
      consequences of heat shock-mediated Ikappa Balpha gene expression in A549 cells.
      METHODS: Nuclear run-on assays demonstrated that heat shock had a small effect on
      transcription of the Ikappa Balpha gene relative to the level of steady state
      Ikappa Balpha mRNA that is seen following heat shock. Accordingly, we determined
      the effect of heat shock on Ikappa Balpha mRNA stability by treating cells with
      actinomycin D to induce transcriptional arrest. RESULTS: The half-life of
      IkappaBalpha mRNA was 36 +/- 7.2 min in control cells and 101 +/- 3.7 min in
      cells subjected to heat shock. These data were consistent with heat shock
      mediated increased stability of Ikappa Balpha mRNA. Heat shock induced activation
      of p38 MAP kinase and inhibition of p38 MAP kinase substantially reduced heat
      shock-dependent expression of Ikappa Balpha mRNA. After a 4 h recovery period
      from heat shock, there was inhibition of tumor necrosis factor-alpha-mediated NF
      kappaB activation. The introduction of an Ikappa Balpha anti-sense
      oligonucleotide reversed this inhibitory effect of heat shock. CONCLUSIONS: We
      conclude that heat shock increases IkappaBalpha gene expression primarily by
      increasing Ikappa Balpha mRNA stability and this effect is partially dependent on
      p38 MAP kinase. The functional consequence of heat shock-mediated Ikappa Balpha
      gene expression is inhibition of NF-kappaB activation.

PMID- 16955246
TI  - Improving the batch-to-batch reproducibility in microbial cultures during
      recombinant protein production by guiding the process along a predefined total
      biomass profile.
AB  - In industry Escherichia coli is the preferred host system for the heterologous
      biosynthesis of therapeutic proteins that do not need posttranslational
      modifications. In this report, the development of a robust high-cell-density fed
      batch procedure for the efficient production of a therapeutic hormone is
      described. The strategy is to guide the process along a predefined profile of the
      total biomass that was derived from a given specific growth rate profile. This
      profile might have been built upon experience or derived from numerical process
      optimization. A surprisingly simple adaptive procedure correcting for deviations
      from the desired path was developed. In this way the batch-to-batch
      reproducibility can be drastically improved as compared to the process control
      strategies typically applied in industry. This applies not only to the biomass
      but, as the results clearly show, to the product titer also.

PMID- 16955247
TI  - Switch of cadherin expression from E- to N-type during the activation of rat
      hepatic stellate cells.
AB  - The activation of hepatic stellate cell (HSC) is a common pathway leading to
      hepatic fibrosis. However, the molecular mechanisms underlying HSC activation
      remain obscure. To elucidate the nature of the HSC activation, we investigated
      the expression of E-cadherin and its switch to N-cadherin during rat HSC
      activation, in vivo and in vitro. Immunohistochemical and immunocytochemical
      staining were performed to identify the expressions of E-cadherin, N-cadherin,
      and beta-catenin in rat HSCs, in vivo and in vitro. Serial changes in the
      expressions of these adhesion molecules during the spontaneous activation of
      cultured rat HSCs were also demonstrated by RT-PCR and by immunoblotting. E
      cadherin and beta-catenin were expressed on opposing cell membranes of GFAP
      positive rat HSCs and adjacent hepatocytes in vivo, and between desmin-positive
      rat HSCs in vitro. With the progression of rat HSC activation in tissue and in
      culture, E-cadherin disappeared gradually, whereas N-cadherin appeared at the
      cell periphery. The results of RT-PCR and immunoblotting were concordant with
      immunocytochemistry findings. In conclusion, resting rat HSCs express E-cadherin
      and beta-catenin both in vivo and in vitro, and E-cadherin switches to N-cadherin
      during HSC activation. These results suggest that HSC activation represents
      transdifferentiation from an epithelial to a mesenchymal phenotype.

PMID- 16955248
TI  - Community-acquired pneumonia and bacteremia caused by an unusual methicillin
      resistant Staphylococcus aureus (MRSA) strain with sequence type 36,
      staphylococcal cassette chromosome mec type IV and Panton-Valentine leukocidin
      genes.

PMID- 16955249
TI  - Effectiveness and nephrotoxicity of intravenous colistin for treatment of
      patients with infections due to polymyxin-only-susceptible (POS) gram-negative
      bacteria.
AB  - The prospective case series study presented here was conducted to assess the
      outcome of patients with infections caused by polymyxin-only-susceptible (POS)
      gram-negative bacteria managed with intravenous colistin. Between July 2003 and
      April 2005 a total of 27 patients were infected with a POS gram-negative
      bacterium and received intravenous colistin at a dose of 2 million international
      units (MIU) (160 mg or 66.7 mg colistin base) every 8 h for a mean (+/-SD)
      duration of 13.9 (+/-7.5) days. Nine patients had ventilator-associated pneumonia
      and received, in addition to the intravenous colistin therapy, 1 MIU (80 mg or
      33.3 mg colistin base) aerosolized colistin every 12 h for a mean (+/-SD)
      duration of 13 (+/-6.5) days. The predominant pathogens were Pseudomonas
      aeruginosa (n = 17) and Acinetobacter baumannii (n = 12); in two patients both
      pathogens were isolated from one clinical specimen. In-hospital mortality and
      clinical response were 15% and 85%, respectively. Colistin-associated
      nephrotoxicity was observed in two of the 27 patients. POS gram-negative
      pathogens represent a major threat for hospitalized patients. Colistin appears to
      be an effective and safe treatment, even in patients with severe underlying
      diseases.

PMID- 16955251
TI  - Role of hospital stay and antibiotic use on Pseudomonas aeruginosa
      gastrointestinal colonization in hospitalized patients.
AB  - The prospective cohort study presented here assessed the risk factors associated
      with Pseudomonas aeruginosa gastrointestinal colonization (PAGIC) in 933 patients
      hospitalized in five different wards in a French university hospital. A total of
      195 patients were colonized. By logistic regression, hospitalization in an
      intensive care unit and length of hospital stay were independent risk factors. A
      significant association was observed between fluoroquinolone use and PAGIC caused
      by an ofloxacin-resistant strain (p < 0.0001), imipenem use and PAGIC caused by
      an imipenem-resistant strain (p < 0.0002) and ceftazidime use and PAGIC caused by
      a ceftazidime-resistant strain (p < 0.02). The ecological impact of antibiotic
      use is of great clinical relevance and clinicians should consider antimicrobial
      resistance in order to limit the development and dissemination of resistant
      microorganisms.

PMID- 16955250
TI  - Cardiobacterium hominis endocarditis: Two cases and a review of the literature.
AB  - Cardiobacterium hominis, a member of the HACEK group (Haemophilus parainfluenzae,
      Haemophilus aphrophilus, and Haemophilus paraphrophilus, Actinobacillus
      actinomycetemcomitans, C. hominis, Eikenella corrodens, and Kingella species), is
      a rare cause of endocarditis. There are 61 reported cases of C. hominis infective
      endocarditis in the English-language literature, 15 of which involved prosthetic
      valve endocarditis. There is one reported case of C. hominis after upper
      endoscopy and none reported after colonoscopy. Presented here are two cases of C.
      hominis prosthetic valve endocarditis following colonoscopy and a review of the
      microbiological and clinical features of C. hominis endocarditis. Patients with
      C. hominis infection have a long duration of symptoms preceding diagnosis (138+/
      128 days). The most common symptoms were fever (74%), fatigue/malaise (53%),
      weight loss/anorexia (40%), night sweats (24%), and arthralgia/myalgia (21%). The
      most common risk factors were pre-existing cardiac disease (61%), the presence of
      a prosthetic valve (28%), and history of rheumatic fever (20%). Of the 61 cases
      reviewed here, the aortic valve was infected in 24 (39%) and the mitral valve in
      19 (31%) patients. The average duration of blood culture incubation before growth
      was detected was 6.3 days (range, 2-21 days). Complications were congestive heart
      failure (40%), central nervous system (CNS) emboli (21%), arrhythmia (16%), and
      mycotic aneurysm (9%). C. hominis is almost always susceptible to beta-lactam
      antibiotics. Ceftriaxone is recommended by the recently published American Heart
      Association guidelines. The prognosis of C. hominis native valve and prosthetic
      valve endocarditis is favorable. The cure rate among 60 patients reviewed was 93%
      (56/60). For prosthetic valve endocarditis, the cure rate was 16/17 (94%). Valve
      replacement was required in 27 (45%) cases.

PMID- 16955252
TI  - Comment on: Evans JMM, Ogston SA, Emslie-Smith A, Morris AD (2006) risk of
      mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of
      patients treated with sulfonylureas and metformin. Diabetologia 49:930-936.

PMID- 16955253
TI  - A lack of evidence for an ecological role of the putative allelochemical (+/-)
      catechin in spotted knapweed invasion success.
AB  - Allelopathy is a notoriously difficult mechanism to demonstrate. There has been a
      recent resurgence of interest in allelopathy because of the work done on the
      invasive weed spotted knapweed and its putative allelochemical, (+/-)-catechin.
      In this study we collected and analyzed soil samples taken from three, long-term
      knapweed infested sites in Montana, USA during the summer and fall of 2005. We
      only detected catechin in all the soil cores at one time point (August, 2005) at
      two of the sites. Field levels from these two sites were nearly three orders of
      magnitude lower than what has previously been reported to cause reduced growth in
      a sensitive native species. Fourteen percent of the remaining soil cores
      contained low but detectable levels (<0.11 ppm) of (+/-)-catechin. Additional
      experiments indicated that soil moisture appears to play a significant role in
      whether or not catechin degrades rapidly or remains in the soil. Adding to
      previous work, this paper sheds doubt on the importance of this chemical in
      spotted knapweed invasion success.

PMID- 16955255
TI  - Association study on chromosome 20q11.21-13.13 locus and its contribution to type
      2 diabetes susceptibility in Japanese.
AB  - Several linkage studies have predicted that human chromosome 20q is closely
      related to type 2 diabetes, but there is no clear evidence that certain
      variant(s) or gene(s) have strong effects on the disease within this region. To
      examine disease susceptibility variant in Japanese, verified SNPs from the
      databases, with a minor allele frequency larger than 0.15, were selected at 10-kb
      intervals across a 19.31-Mb region (20q11.21-13.13), which contained 291 genes,
      including hepatocyte nuclear factor 4alpha (HNF4alpha). As a result, a total of
      1,147 SNPs were genotyped with TaqMan assay using 1,818 Japanese samples. By
      searching for HNF4alpha as a representative disease-susceptible gene, no variants
      of HNF4alpha were strongly associated with disease. To identify other genetic
      variant related with disease, we designed an extensive two-stage association
      study (725 first and 1,093 second test samples). Although SNP1146 (rs220076) was
      selected as a landmark within the 19.31 Mb region, the magnitude of the nominal P
      value (P = 0.0023) was rather weak. Subsequently, a haplotype-based association
      study showed that two common haplotypes were weakly associated with disease. All
      of these tests resulted in non-significance after adjusting for Bonferroni's
      correction and the false discovery rate to control for the impact of multiple
      testing. Contrary to the initial expectations, we could not conclude that certain
      SNPs had a major effect on this promising locus within the framework presented
      here. As a way to extend our observations, we emphasize the importance of a
      subsequent association study including replication and/or meta-analysis in
      multiple populations.

PMID- 16955256
TI  - Microbial interactions in Staphylococcus epidermidis biofilms.
AB  - Medical device-associated infections, most frequently caused by coagulase
      negative staphylococci, especially Staphylococcus epidermidis, are of increasing
      importance in modern medicine. The formation of adherent, multilayered bacterial
      biofilms is the most important factor in the pathogenesis of these infections,
      which regularly fail to respond to appropriate antimicrobial therapy. Progress in
      elucidating the factors functional in elaboration of S. epidermidis biofilms and
      the regulation of their expression with a special emphasis on the role of quorum
      sensing are reviewed. Significant progress has been made in recent years, which
      provides the rationale for developing better preventive, therapeutic and
      diagnostic measures.

PMID- 16955257
TI  - Identification of in vitro metabolites of JWH-015, an aminoalkylindole agonist
      for the peripheral cannabinoid receptor (CB2) by HPLC-MS/MS.
AB  - The in vitro microsomal metabolism of JWH-015, a ligand that exhibits a high
      binding affinity at the peripheral cannabinoid receptor CB(2), has been studied.
      A total of 22 metabolites were identified and structurally characterized. The
      metabolites are products of: 1) monohydroxylation on the naphthalene ring (m/z
      344, M20 and M21), indole ring (m/z 344, M17 and M18), or the N-alkyl group (m/z
      344, M14); 2) arene oxidation leading to dihydrodiols (m/z 362, M12 and M15); 3)
      dihydroxylation on the naphthalene ring (m/z 360, M7) or indole ring (m/z 360,
      M13), resulting from a combination of monohydroxylations on both the naphthalene
      and indole rings (m/z 360, M16), or a combination of monohydroxylations on the
      naphthalene ring and on the N-propyl group (m/z 360, M9); 4) trihydroxylation
      (m/z 378, M1, M3, M4, M6, and M10); 5) N-dealkylation (m/z 286, M19); 6) N
      dealkylation and monohydroxylation on the naphthalene ring (m/z 302, M11); 7) N
      dealkylation and dihydrodiol formation from arene oxidation (m/z 320, M2 and M5);
      8) dehydrogenation after monohydroxylation on the N-alkyl group (m/z 326, M22);
      9) dehydrogenation and monohydroxylation on the indole ring (m/z 342, M8).

PMID- 16955258
TI  - Comparison of two solid-phase microextraction methods for the quantitative
      analysis of VOCs in indoor air.
AB  - Competitive adsorption on adsorptive solid-phase microextraction (SPME) fibres
      implies careful determination of operating conditions for reliable quantitative
      analysis of VOCs in indoor air. With this objective, two analytical approaches,
      involving non-equilibrium and equilibrium extraction, were compared. The average
      detection limit obtained for GC-MS analysis of nine VOCs by the equilibrium
      method is 0.2 microg m(-3), compared with 1.9 microg m(-3) with the non
      equilibrium method. The effect of the relative humidity of the air on the
      calibration plots was studied, and shown to affect acetone adsorption only.
      Hence, the concentrations that can be accurately determined are up to 9 micromol
      m(-3). The methods were then applied to indoor air containing different
      concentrations of VOCs. The non-equilibrium method, involving short extraction
      time, can be used for detection of pollution peaks whereas equilibrium extraction
      is preferable for measurement of sub-microg m(-3) ground concentration levels.

PMID- 16955259
TI  - Comparing and combining NMR spectroscopy and mass spectrometry in metabolomics.

PMID- 16955260
TI  - Advances in immunoanalysis of single cells with capillary electrophoresis.

PMID- 16955261
TI  - Single-cell manipulation and analysis using microfluidic devices.

PMID- 16955262
TI  - Multiple sampling in single-cell enzyme assays using capillary electrophoresis
      with laser-induced fluorescence detection.

PMID- 16955263
TI  - Choosing one from the many: selection and sorting strategies for single adherent
      cells.

PMID- 16955264
TI  - Cellular manipulations in microvortices.

PMID- 16955265
TI  - Proteomics of synapse.

PMID- 16955266
TI  - Mass spectrometric charting of neuropeptides in arthropod neurons.

PMID- 16955267
TI  - Trifluoperazine protects brain plasma membrane Ca(2+)-ATPase from oxidative
      damaging.
AB  - In the central nervous system (CNS), a number of different pathological processes
      such as necrosis, Parkinson's and Alzheimer's diseases are related to disturbance
      in calcium homeostasis associated with oxidative stress. Here we compare the
      susceptibility of rat brain plasma membrane Ca(2+)-ATPase (PMCA) and sarco
      endoplasmic reticulum Ca(2+)-ATPase (SERCA) isoforms to in vitro oxidative
      stress, and investigate a putative role of trifluoperazine (TFP), an
      antipsychotic drug that is also a powerful inhibitor of Ca(2+)-transporter
      proteins, in protecting these enzymes. It is shown that, in rat brain, PMCA is
      very sensitive to the damage induced by preincubation with Fe(2+)-ascorbate, or
      Fe(2+)-ascorbate plus H2O2, while SERCA is resistant. Inhibition of PMCA activity
      promoted by Fe(2+)/ascorbate medium is fully prevented by the presence of microM
      concentrations of either butylated hydroxytoluene (BHT) or TFP, but only
      partially protected, or reversed, by dithiothreitol (DTT), pointing to some
      protein cysteine(s) as one of the main targets for a lipid peroxidation-dependent
      damaging mechanism. However, when 0.5-1 mM H2O2 is added together with
      Fe(2+)/ascorbate, both BHT and TFP only partially prevent ATPase activity
      inhibition, and DTT does not confer any protection, suggesting two possible
      additional mechanisms involving both lipid peroxidation and direct damage to PMCA
      at amino acid residues other than cysteines. A possible use of micromolar
      concentrations of TFP as a direct antioxidant protector for PMCA under oxidative
      stress conditions is discussed.

PMID- 16955268
TI  - Shaping the pupil's response to light in the hooded rat.
AB  - The contribution of iris muscle steady state and dynamic response characteristics
      to the shaping of the pupil response to light in the hooded rat were studied
      using electrical stimulation of the parasympathetic fibers in the III nerve. The
      waveforms of pupillary contractions to single or brief trains of electrical
      impulses applied to the III nerve were virtually identical to those elicited with
      short duration light flashes. Individual contractions could be resolved at
      stimulation rates of 2 Hz and below, and the size of the contractions increased
      with the decrease in frequency. The pupil responded to long trains of stimuli
      above 2 Hz with smooth tonic contractions. Steady state contraction amplitude was
      linearly related to log stimulation frequency. The mean time constant of pupil
      constriction to stimulus trains was 1.41 s (SD +/- 0.71 s) and the shortest mean
      latency was 292 ms (SD +/- 30 ms). The fastest mean latency of pupil constriction
      to the brightest light flash used was 295 ms. In contrast, the time constant of
      pupillary dilation was 7 s (SD +/- 1.4 s) and the shortest latency was 485 ms (SD
      +/- 74 ms). Therefore, the sluggish dynamic properties of the iris musculature
      are responsible for the asymmetries in pupil contraction, dilation, and latencies
      as well as low flicker fusion frequency and constriction amplitude
      characteristics of pupil responses to light.

PMID- 16955269
TI  - Development of head movement propensity in 4-15 year old children in response to
      visual step stimuli.
AB  - Head movement frequency of children in response to horizontal step stimulus is
      investigated. The aim is to determine if there is a correlation between the age
      of the child and the frequency of head movements made to visual step stimuli
      presented at a fixed distance. Also of importance is whether there is a period of
      rapid change in the frequency of head movements, and if so, what factors could be
      influencing this change. Seventy-three participants, between the ages of 4 and 15
      years were requested to "look at a spot of light" in response to step stimuli
      which varied in size from 5 to 60 degrees. Eye and head movements were recorded
      with a video based eye tracker (EL-Mar 2020) equipped with a Flock of Birds head
      tracker. Frequency of head movements was calculated for each participant and
      averaged across participants for each age group. Average head movement frequency
      was then plotted as a function of age. The frequency and variability of head
      movements decreases as a function of age. This decrease is linear between the
      ages of 4 and 15 years (y = -1.465x + 22.58; R(2) = 0.4378; F = 26.48; P <
      0.0001). More head movements are made in response to larger step sizes than to
      smaller ones for all ages. The gradual decrease in frequency of head movements in
      response to step stimuli suggests that a specific environmental event, such as
      reading, is not the cause of the decline. Improved efficiency of eye movements
      could be due to pre-programmed factors related to neurological development.
      Alternatively, cognitive factors may be involved. Children may actually learn
      that utilizing their head for gaze shifts is more energy and time consuming, than
      merely using the eyes alone.

PMID- 16955270
TI  - Amino acids regulate salinity-induced potassium efflux in barley root epidermis.
AB  - The amino acid content increases substantially in salt-stressed plants. The
      physiological relevance of this phenomenon remains largely unknown. Using the
      MIFE ion flux measuring technique, we studied the effects of physiologically
      relevant concentrations of 26 amino acids on NaCl-induced K(+) flux from barley
      root epidermis. We show that 21 (of 26) amino acids caused a significant
      mitigation of the NaCl-induced K(+) efflux, while valine and ornithine
      substantially enhanced the detrimental effects of salinity on K(+) homeostasis.
      Our results suggest that physiologically relevant concentrations of free amino
      acids might contribute to plant adaptive responses to salinity by regulating K(+)
      transport across the plasma membrane, thus enabling maintenance of an optimal
      K(+)/Na(+) ratio as opposed to being merely a symptom of plant damage by stress.
      Investigating the specific mechanisms of such amelioration remains a key issue
      for future studies.

PMID- 16955271
TI  - Magnetic intensity affects cryptochrome-dependent responses in Arabidopsis
      thaliana.
AB  - Cryptochromes are blue-light absorbing photoreceptors found in many organisms
      where they have been involved in numerous growth, developmental, and circadian
      responses. In Arabidopsis thaliana, two cryptochromes, CRY1 and CRY2, mediate
      several blue-light-dependent responses including hypocotyl growth inhibition. Our
      study shows that an increase in the intensity of the ambient magnetic field from
      33-44 to 500 muT enhanced growth inhibition in A. thaliana under blue light, when
      cryptochromes are the mediating photoreceptor, but not under red light when the
      mediating receptors are phytochromes, or in total darkness. Hypocotyl growth of
      Arabidopsis mutants lacking cryptochromes was unaffected by the increase in
      magnetic intensity. Additional cryptochrome-dependent responses, such as blue
      light-dependent anthocyanin accumulation and blue-light-dependent degradation of
      CRY2 protein, were also enhanced at the higher magnetic intensity. These findings
      show that higher plants are sensitive to the magnetic field in responses that are
      linked to cryptochrome-dependent signaling pathways. Because cryptochromes form
      radical pairs after photoexcitation, our results can best be explained by the
      radical-pair model. Recent evidence indicates that the magnetic compass of birds
      involves a radical pair mechanism, and cryptochrome is a likely candidate for the
      avian magnetoreception molecule. Our findings thus suggest intriguing parallels
      in magnetoreception of animals and plants that appear to be based on common
      physical properties of photoexcited cryptochromes.

PMID- 16955272
TI  - Inorganic phosphate uptake in intact vacuoles isolated from suspension-cultured
      cells of Catharanthus roseus (L.) G. Don under varying Pi status.
AB  - Inorganic phosphate (Pi) uptake across the vacuolar membrane of intact vacuoles
      isolated from Catharanthus roseus suspension-cultured cells was measured. Under
      low Pi status, Pi uptake into the vacuole was strongly activated compared to high
      Pi status. Since Pi uptake across the vacuolar membrane is correlated with H+
      pumping, we examined the dependency of H+ pumping on plant Pi status. Both H+
      pumping and the activities of the vacuolar H+-pumps, the V-type H+-ATPase and the
      H+-PPase were enhanced under low Pi status. Despite this increase in H+ pumping,
      Western blot analysis showed no distinct increase in the amount of proton pump
      proteins. Possible mechanisms for the activation of Pi uptake into the vacuole
      under low Pi status are discussed.

PMID- 16955273
TI  - A cortical band of gelatinous fibers causes the coiling of redvine tendrils: a
      model based upon cytochemical and immunocytochemical studies.
AB  - A cortical band of fiber cells originate de novo in tendrils of redvine
      [Brunnichia ovata (Walt.) Shiners] when these convert from straight, supple young
      filaments to stiffened coiled structures in response to touch stimulation. We
      have analyzed the cell walls of these fibers by in situ localization techniques
      to determine their composition and possible role(s) in the coiling process. The
      fiber cell wall consists of a primary cell wall and two lignified secondary wall
      layers (S(1) and S(2)) and a less lignified gelatinous (G) layer proximal to the
      plasmalemma. Compositionally, the fibers are sharply distinct from surrounding
      parenchyma as determined by antibody and affinity probes. The fiber cell walls
      are highly enriched in cellulose, callose and xylan but contain no
      homogalacturonan, either esterified or de-esterified. Rhamnogalacturonan-I (RG-I)
      epitopes are not detected in the S layers, although they are in both the
      gelatinous layer and primary wall, indicating a further restriction of RG-I in
      the fiber cells. Lignin is concentrated in the secondary wall layers of the fiber
      and the compound middle lamellae/primary cell wall but is absent from the
      gelatinous layer. Our observations indicate that these fibers play a central role
      in tendril function, not only in stabilizing its final shape after coiling but
      also generating the tensile strength responsible for the coiling. This theory is
      further substantiated by the absence of gelatinous layers in the fibers of the
      rare tendrils that fail to coil. These data indicate that gelatinous-type fibers
      are responsible for the coiling of redvine tendrils and a number of other
      tendrils and vines.

PMID- 16955274
TI  - rAAV-mediated angiogenin gene transfer induces angiogenesis and modifies left
      ventricular remodeling in rats with myocardial infarction.
AB  - In vitro studies have demonstrated that bovine angiogenin (ANG) significantly
      stimulates both the migration of endothelial cells and the formation of tubelike
      structures. The aim of this study was to explore whether ANG gene transfer could
      enhance vascularization, modify left ventricular remodeling, and attenuate
      cardiac dysfunction in rats with myocardial infarction (MI). We constructed a
      recombinant adeno-associated virus vector encoding the ANG gene (rAAV-ANG) and
      evaluated its angiogenic potential after regional transfection by intramyocardial
      injection immediately after left anterior descending artery ligation in rats.
      Four weeks after coronary artery ligation, rAAV-ANG transfection upregulated the
      myocardium ANG protein expression level in both normal and MI rats, and
      immunohistochemistry showed that the overexpressed ANG was distributed in the
      cytoplasm of cardiomyocytes. In rats with MI, rAAV-ANG treatment altered left
      ventricular remodeling, as indicated by a decrease in left ventricular end
      diastolic diameter, left ventricular end systolic diameter, cardiomyocyte
      diameter, ventricular weight to body weight ratio and interstitial fibrosis
      infiltration. We also found an increase in capillary density and partly restored
      cardiac function in the group receiving rAAV-ANG treatment. These results
      confirmed that in rats with MI, ANG gene transfer could induce angiogenesis,
      alter left ventricular remodeling, and attenuate cardiac dysfunction. This study
      provides a new choice of treatment for ischemic heart disease.

PMID- 16955275
TI  - Short-term hyperthermia prevents activation of proinflammatory genes in
      fibroblast-like synoviocytes by blocking the activation of the transcription
      factor NF-kappaB.
AB  - Fibroblast-like synoviocytes (FLS) play a key role in the genesis of rheumatoid
      arthritis (RA). FLS are among the most versatile cells with the potential to
      activate an array of genes that are able to initiate and propagate inflammation
      in RA-affected joints. Controlling activation of FLS might hold the key to
      restraining inflammation in RA-affected joints. In this study, we investigate the
      effect and mechanisms of short-term hyperthermia on a series of proinflammatory
      genes in FLS. In vitro experiments demonstrate that exposure of FLS to elevated
      temperatures for the duration of 30 min prevents activation of a series of genes
      with proinflammatory properties. Exposure to hyperthermia reduces IL-1beta
      induced prostaglandin E2 release, suppresses activation of the adhesion molecules
      VCAM-1, ICAM-1, the cytokines TNFalpha, IL-1alpha, IL-1beta, IL-8 as well as COX
      2 protein synthesis. Real time reverse transcriptase-polymerase chain reaction
      showed that hyperthermia altered gene expression at the transcriptional level.
      The amount and the duration of inhibition is gene-specific and lasts for up to 25
      h. As to the mechanism of inhibition, electrophoretic mobility shift assay
      experiments demonstrated that exposure of FLS to hyperthermia prevents IL-1beta
      induced NF-kappaB translocation and subsequent DNA binding. Many mechanisms have
      been shown to be involved in hyperthermia-mediated effects on NF-kappaB-DNA
      interactions. We demonstrate by Western blot experiments that in FLS,
      hyperthermia prevents the phosphorylation and subsequent degradation of
      IkappaBalpha, therefore retaining the NF-kappaB complex in the cytoplasm.
      Carefully controlled in vivo tests are certainly needed before one can take full
      advantage of those phenomena; however, the ease by which the temperature in
      joints can be modulated might offer an opportunity for manipulating inflammatory
      processes in joints by simple balneological means.

PMID- 16955276
TI  - Patterns of association between PPARgamma genetic variation and indices of
      adiposity and insulin action in African-Americans and whites: the CARDIA Study.
AB  - We performed a combination of single-variant- and haplotype-based analyses to
      investigate the association of peroxisome-proliferator-activated receptor gamma
      (PPARgamma) gene sequence variation with indices of adiposity, including body
      mass index (BMI) and waist girth, as well as insulin action, including fasting
      blood glucose and insulin levels. Nine polymorphisms, selected based on race
      specific pairwise linkage disequilibrium relations and/or potential functional
      relevance, were assayed in 3,875 African-American and white young adults from the
      Coronary Artery Risk Development in Young Adults Study. These polymorphisms were
      C25819G (C-681G), C65746G (Pro12Ala), G67222A, A69208G, G81556T, T95872C,
      T115432G, C127599T, and C148157T (C1431T). They defined seven and six common
      haplotypes in African-Americans and whites, respectively. Patterns of
      associations of PPARgamma genetic variation with the metabolic traits differed
      between the two racial groups, with some exceptions. Haplotype CCGGCTCC was
      associated with a significant reduction in glucose levels in both racial groups
      (P<0.001 in each group), and the G69208 allele was associated with lower glucose
      levels in lean African-Americans and in whites (both P=0.02). Two haplotypes,
      relatively unique to whites, were associated with measures of adiposity and
      glucose levels. Two haplotypes, relatively unique to African-Americans, were
      associated with glucose levels. There were no significant effects of PPARgamma
      haplotypes on measures of body size in this racial group, but a novel
      polymorphism, G67222A, significantly modulated the relation between BMI and
      glucose levels (P interaction, 0.003). This study provides evidence that
      variants, other than Pro12Ala, influence variation in body size and indices of
      insulin action. It underscores the role of genetic and environmental contexts in
      shaping the patterns of associations of PPARgamma sequence variants with
      metabolic traits in human populations.

PMID- 16955277
TI  - Structural determinants for G-protein activation and specificity in the third
      intracellular loop of the thyroid-stimulating hormone receptor.
AB  - The selectivity of G-protein recognition is determined by the intracellular loops
      (ICLs) of seven-transmembrane-spanning receptors. In a previous study, we have
      shown that the N-terminal and central portions of ICL2 from F525 to D530
      participate in dual Galphas-/Galphaq-protein activation by the thyroid
      stimulating hormone receptor (TSHR). ICL3 is another major determinant for G
      protein activation. Therefore, the aim of our study was to identify important
      amino acids within ICL3 of the TSHR to gain insight in more detail about its
      specific function for Galphas- and Galphaq-protein activation and selectivity.
      Single-alanine substitutions of residues in the N-terminal, middle, and C
      terminal region of ICL3 were generated. N-terminal residues Y605 and V608 and C
      terminal positions K618, K621, and I622 were identified as selectively important
      for Galphaq activation, whereas mutations in the center of ICL3 had no effect on
      TSHR signaling. Our findings provide evidence for an amino acid pattern in the N-
      and C-terminal part of ICL3, which is involved in Galphaq-mediated signaling.
      Furthermore, molecular modeling of interaction of TSHR ICL2 and 3 with Galphaq
      suggests three potential contact sites: TSHR C-terminal ICL3 with beta5-6 loop of
      Galphaq, TSHR ICL2 residues I523-R531 with beta2-3 loop and N-terminal helix of
      Galphaq, and TSHR ICL2/transmembrane helix (TMH) 3+ICL3/TMH6 with C-terminal tail
      of Galphaq.

PMID- 16955278
TI  - Regression of left ventricular hypertrophy in children with antihypertensive
      therapy.
AB  - Left ventricular hypertrophy (LVH) is a complication of hypertension that has
      received great attention in the adult population. Large-scale randomized control
      studies in adults have demonstrated that LVH regresses in response to
      pharmacologic intervention. While it is known that LVH occurs as a complication
      of hypertension in the pediatric population, few studies have focused on its
      regression with pharmacological intervention. We report on three cases of
      hypertension-induced LVH in the pediatric population and its regression after
      treatment with antihypertensive medications. This report brings to light the need
      for larger, prospective studies on the incidence, natural history, and treatment
      of LVH associated with hypertension in the pediatric population.

PMID- 16955279
TI  - C1q nephropathy in association with Gitelman syndrome: a case report.
AB  - There have been rare reports of glomerulopathies developing in patients with
      Bartter syndrome (BS) and its milder variant, Gitelman syndrome (GS). We present
      the first case of C1q nephropathy (C1qN) in an African American child with GS.
      This child was diagnosed with GS at 9 years of age and subsequently developed
      nephrotic range proteinuria 3 years later. Renal biopsy revealed mesangial
      hypercellularity and focal segmental glomerulosclerosis (FSGS). The segmental
      lesions were generally located at the vascular pole. Dominant C1q (2+) staining
      along with IgG (1-2+) was demonstrated in the mesangium, which correlated with
      scattered electron dense mesangial deposits demonstrated by electron microscopy.
      Treatment with an angiotensin-converting enzyme inhibitor led to an improvement
      in proteinuria to near-normal values (urine protein/creatinine ratio down to
      0.5), but the creatinine clearance declined to approximately 58 ml/min/1.73 m(2).
      This case highlights the possible association between the milder hypokalemic
      tubulopathy, GS, and glomerular disease, including C1qN. Prompt evaluation of
      proteinuria with renal biopsy in these patients is recommended to detect
      significant glomerular pathology. Further research is needed to define risk
      factors for this complication.

PMID- 16955280
TI  - Renal hypouricemia in school-aged children: screening of serum uric acid level
      before physical training.
AB  - We present two cases of a 12-year-old Japanese boy and a 14-year-old Japanese
      girl who had exercise-induced acute renal failure (ARF). They experienced general
      fatigue, nausea/vomiting, and vague discomfort in the abdomen after physical
      exercise at school. In case of the boy, abdominal pain subsided, but renal
      dysfunction lasted 17 days, with peak levels of creatinine 9.4 mg/dl and uric
      acid 11.3 mg/dl. On the other hand, as the girl had suffered from hypouricemia
      before, she followed a doctor's guidance on prevention of ARF. Consequently, she
      was promptly diagnosed as having exercise-induced ARF associated with
      hypouricemia, and rapidly recovered from ARF within a week. The difference
      between their clinical courses suggested a possibility that previous laboratory
      evaluation of serum uric acid assisted in the management of exercise-induced ARF
      associated with hypouricemia. School-aged children, especially Japanese and
      Asian, may be advised to have their serum uric acid measured before starting
      physical training at school.

PMID- 16955281
TI  - Nephrotoxicity with cyclooxygenase 2 inhibitor use in children.
AB  - The nephrotoxic potential of anti-inflammatory drugs alone and in compound
      preparations has been known for over fifty years. Nephrotoxicity associated with
      selective cyclooxygenase 2 (COX-2) inhibitor use is reported in adult patients
      but not in children. We present here the first report of reversible acute renal
      failure associated with the COX-2 inhibitor rofecoxib (Vioxx) in three children.
      Patient 1, an 18 month old girl with neonatal Bartter syndrome, developed acute
      renal failure with a peak creatinine of 1.9 mg/dl (164 micromol/l) and severe
      hyperkalemic metabolic acidosis. Patient 2, a 14 year old boy with a history of
      rheumatic fever, developed acute renal failure with a peak creatinine of 2.7
      mg/dl (240 micromol/l). While patient 3, a healthy 14 year old girl, developed
      acute renal failure and tubulointerstitial nephritis confirmed on renal biopsy
      with a peak creatinine of 3.3 mg/dl (287 micromol/L). All children had been
      taking non-selective non-steroidal anti-inflammatory drugs (NSAID's) immediately
      prior to rofecoxib use. Renal function returned to normal within one week in all
      three patients and has remained normal at follow-up. This paper highlights the
      nephrotoxic risk of COX-2 inhibitor use in the pediatric population.

PMID- 16955283
TI  - Insulin sensitization induced by oral cicletanine in conscious rabbits.
AB  - The endogenous insulin sensitizing machinery termed the hepatic insulin
      sensitizing substance (HISS) mechanism has been shown to be nitrergic and linked
      to sensory fibers in the anterior hepatic plexus. We studied whether this
      mechanism could pharmacologically be exploited by cicletanine, a cGMP-PDE
      inhibitor antihypertensive drug, in conscious rabbits. Whole body insulin
      sensitivity and peripheral glucose uptake were determined by hyperinsulinaemic
      euglycaemic glucose clamping, and cardiac radiolabelled deoxyglucose (DOG) uptake
      in neurogenic, achieved by perineurial capsaicin treatment of the anterior
      hepatic plexus through defunctionalization of hepatic sensory fibers, and
      metabolic, induced by dietary hypercholesterolemia, insulin resistance models
      after single oral doses of cicletanine (3, 10 and 30 mg kg(-1)) or rosiglitazone
      (3 mg kg(-1)). The effect of cicletanine on cardiac and vascular tissue NO, cGMP,
      cAMP was measured by means of spin trapping technique and radioimmunoassay,
      respectively. Insulin sensitivity and peripheral DOG uptake were significantly
      increased by 10 and 30 mg kg(-1) cicletanine in both healthy and
      hypercholesterolaemic rabbits, but not in those with neurogenic insulin
      resistance. Rosiglitazone had no effect in healthy and neurogenic insulin
      resistant rabbits although it improved insulin sensitivity in
      hypercholesterolemic animals. The 10 mg kg(-1) cicletanine dose induced no change
      in either cardiac or vascular tissue NO, cGMP or cAMP concentrations.
      Nevertheless, at a dose of 30 mg kg(-1) producing an insulin sensitizing effect
      of approximately the same amplitude as seen with 10 mg kg(-1), the drug
      significantly increased tissue NO and cGMP concentrations. Oral cicletanine
      attains its insulin sensitizing effect at doses lower than those necessary to
      activate the NO-cGMP pathway in the cardiovascular system. This metabolic effect
      requires functional integrity of hepatic sensory nerves.

PMID- 16955282
TI  - In vivo imaging of serotonin transporter occupancy by means of SPECT and
      [123I]ADAM in healthy subjects administered different doses of escitalopram or
      citalopram.
AB  - BACKGROUND: Escitalopram is a dual serotonin reuptake inhibitor (SSRI) approved
      for the treatment of depression and anxiety disorders. It is the S-enantiomer of
      citalopram, and is responsible for the serotonin reuptake activity, and thus for
      its pharmacological effects. Previous studies pointed out that clinically
      efficacious doses of other SSRIs produce an occupancy of the serotonin reuptake
      transporter (SERT) of about 80% or more. The novel radioligand [123I]ADAM and
      single photon emission computer tomography (SPECT) were used to measure midbrain
      SERT occupancies for different doses of escitalopram and citalopram. METHODS:
      Twenty-five healthy subjects received a single dose of escitalopram [5 mg (n=5),
      10 mg (n=5), and 20 mg (n=5)] or citalopram [(10 mg (n=5) and 20 mg (n=5)].
      Midbrain SERT binding was measured with [(123)I]ADAM and SPECT on two study days,
      once without study drug and once 6 h after single dose administration of the
      study drug. The ratio of midbrain-cerebellum/cerebellum was the outcome measure
      (V3") for specific binding to SERT in midbrain. Subsequently, SERT occupancy
      levels were calculated using the untreated baseline level for each subject. An
      Emax model was used to describe the relationship between S-citalopram
      concentrations and SERT occupancy values. Additionally, four subjects received
      placebo to determine test-retest variability. RESULTS: Single doses of 5, 10, or
      20 mg escitalopram led to a mean SERT occupancy of 60+/-6, 64+/-6, and 75+/-5%,
      respectively. SERT occupancies for subjects treated with single doses of 10 and
      20 mg citalopram were 65+/-10 and 70+/-6%, respectively. A statistically
      significant difference was found between SERT occupancies after application of 10
      and 20 mg escitalopram, but not for 10 and 20 mg citalopram. There was no
      statistically significant difference between the SERT occupancies of either 10 mg
      citalopram or 10 mg escitalopram, or between 20 mg citalopram and 20 mg
      escitalopram. Emax was slightly higher after administration of citalopram (84%)
      than escitalopram (79%). In the test-retest study, a mean SERT "occupancy" of 4%
      was found after administration of placebo, the intraclass correlation coefficient
      was 0.92, and the repeatability coefficient was 0.25. CONCLUSION: SPECT and
      [123I]ADAM were used to investigate SERT occupancies after single doses of
      escitalopram or citalopram. The test-retest study revealed good reproducibility
      of SERT quantification. Similar SERT occupancies were found after administration
      of equal doses (in respect to mg) of escitalopram and citalopram, giving indirect
      evidence for a fractional blockade of SERT by the inactive R-citalopram.

PMID- 16955285
TI  - Optical coherence tomography and electro-oculogram abnormalities in X-linked
      retinitis pigmentosa.
AB  - PURPOSE: To determine the correlations between morphological optical coherence
      tomography (OCT) and electrophysiological electro-oculogram (EOG) alterations in
      families with X-linked retinitis pigmentosa (XLRP). DESIGN: Observational case
      series. PARTICIPANTS AND METHODS: About 32 eyes of 16 members of four different
      families: Seven obligate carriers, four affected male homozygotes and five
      unaffected females underwent ophthalmologic completed exams including EOG and
      OCT. All the subjects were previously tested with genetic analysis. The results
      were statistically analysed. RESULTS: The abnormalities in OCT were detected in
      all carriers and affected males consisting of macular edema and increased RPE
      reflectivity compared to no alterations in unaffected females. The EOG was flat
      in all affected males; distinctly abnormal in eight eyes of obligate carriers;
      normal in two eyes of obligate carriers and in all unaffected females. In two
      obligate carriers, the EOG was not performed due to a nuclear cataract. The
      correlations between OCT and EOG alterations were statistically significant.
      CONCLUSIONS: The OCT and EOG were demonstrated to be useful methods to identify
      the minimal alterations in carriers of X-linked retinitis pigmentosa.

PMID- 16955284
TI  - Protection against myocardial ischemia/reperfusion injury by short-term diabetes:
      enhancement of VEGF formation, capillary density, and activation of cell survival
      signaling.
AB  - The aims of this study were to determine effects of diabetes duration on
      myocardial ischemia/reperfusion (I/R) injury and test whether time-dependent
      differences in sensitivity of the streptozotocin diabetic rat heart to I/R are
      related to differences in vascular density, levels of vascular endothelial growth
      factor (VEGF) or endothelial nitric oxide synthase (eNOS) expression, NO
      formation, activation of Akt, and/or oxidative stress. After 2 or 6 weeks of
      streptozotocin-induced diabetes, I/R injury was induced by occlusion (30 min) and
      reperfusion of the left descending coronary artery. After 2 weeks of diabetes,
      infarct size and cleavage of caspase-3, a proapoptosis signal, were decreased as
      compared with normoglycemic controls or rats that had been diabetic for 6 weeks,
      whereas capillary density and levels of VEGF and eNOS protein and cardiac NO(x)
      levels were all increased. Phosphorylation of Akt, a prosurvival signal, was also
      significantly increased after 2 weeks of diabetes. Cardiac lipid peroxidation was
      comparable to controls after 2 weeks of diabetes, whereas levels of
      nitrotyrosine, a peroxynitrite biomarker, were reduced. After 6 weeks of
      diabetes, lipid peroxidation was increased and levels of VEGF and plasma NO were
      reduced as compared with controls or rats diabetic for 2 weeks. Our results
      indicate endogenous cardioprotective mechanisms become transiently activated in
      this early stage of diabetes and that this may protect the heart from I/R injury
      through enhancement of VEGF and eNOS expression, NO formation, activation of cell
      survival signals, and decreased oxidative stress.

PMID- 16955286
TI  - Local adaptation in the monocarpic perennial Carlina vulgaris at different
      spatial scales across Europe.
AB  - Spatial variation in environmental conditions can lead to local adaptation of
      plant populations, particularly if gene flow among populations is low. Many
      studies have investigated adaptation to contrasting environmental conditions, but
      little is known about the spatial scale of adaptive evolution. We studied
      population differentiation and local adaptation at two spatial scales in the
      monocarpic grassland perennial Carlina vulgaris. We reciprocally transplanted
      seedlings among five European regions (northwestern Czech Republic, central
      Germany, Luxembourg, southern Sweden and northwestern Switzerland) and among
      populations of different sizes within three of the regions. We recorded survival,
      growth and reproduction over three growing periods. At the regional scale,
      several performance traits and the individual fitness of C. vulgaris were highest
      if the plants were grown in their home region and they decreased with increasing
      transplant distance. The effects are likely due to climatic differences that
      increased with the geographical distance between regions. At the local scale,
      there were significant interactions between the effects of the population of
      origin and the transplant site, but these were not due to an enhanced performance
      of plants at their home site and they were not related to the geographical or
      environmental distance between the site of origin and the transplant site. The
      size of the population of origin did not influence the strength of local
      adaptation. The results of our study suggest that C. vulgaris consists of
      regionally adapted genotypes, and that distance is a good predictor of the extent
      of adaptive differentiation at large scales ( > 200 km) but not at small scales.
      We conclude that patterns of local adaptation should be taken into account for
      the efficient preservation of genetic resources, when assessing the status of a
      plant species and during conservation planning.

PMID- 16955287
TI  - Phenotypic plasticity of reproductive traits in response to food availability and
      photoperiod in white-footed mice (Peromyscus leucopus).
AB  - Although most temperate-zone mammals are seasonal breeders, many populations
      display variation in winter reproductive phenotype. For most mammals, the primary
      environmental cues regulating reproductive status are food availability and
      photoperiod, and these two factors can interact in their effect. Low food
      availability is primarily thought to suppress reproduction by reducing body mass
      and thereby forcing energy allocations to survival alone. However, because most
      small mammals rely on an increase in food intake rather than stored nutrients for
      reproduction, we hypothesized that food availability could act as a signal for
      low resource availability and affect reproduction even when body condition was
      not affected. We tested the prediction that restricted food access, without
      reduced body mass, could alter reproductive responses to short photoperiod. We
      used genetically distinct lines of white-footed mice (Peromyscus leucopus)
      derived from a wild population with genetic variation in the neuroendocrine
      pathway that regulates reproduction in response to environmental cues. The lines
      were created by artificial selection on gonad size in short photoperiods.
      Individuals from one line strongly suppress gonadal development in response to
      short photoperiods, while individuals from the other line suppress gonadal
      development weakly or not at all. Unresponsive individuals from the selected and
      an unselected control line were exposed to an intermittent food access protocol
      that did not affect body mass and only slightly reduced total food intake. We
      found that restricting food access caused reproductive suppression in short
      photoperiods but not long photoperiods, with no decrease in body mass. These
      results provide evidence for an interaction between food and photoperiod that is
      not dependent upon body condition or energy balance. The results also demonstrate
      plasticity in the reproductive response to photoperiod of otherwise
      reproductively nonphotoperiodic white-footed mice.

PMID- 16955289
TI  - Predators induce egg retention in prey.
AB  - To prevent predation on their eggs, prey often avoid patches occupied by
      predators. As a result, they need to delay oviposition until they reach predator
      free patches. Because many species allocate energy to egg production in a
      continuous fashion, it is not clear what kind of mechanism prey use to delay
      oviposition. We used females of the phytoseiid mite Neoseiulus cucumeris to study
      these mechanisms. Females were placed in patches with pollen, a food source they
      use for egg production, and they were exposed to another phytoseiid mite,
      Iphiseius degenerans, which is an intraguild predator of N. cucumeris juveniles.
      We found that the oviposition of N. cucumeris females on patches with the
      predator was lower than on patches without the predator. Cues left by the
      intraguild predator were not sufficient to elicit such behaviour. Females of N.
      cucumeris reduced oviposition when exposed to the predator by retaining the egg
      inside their body, resulting in a lower developmental rate once these eggs were
      laid. Hence, females are capable of retaining eggs, but the development of these
      eggs continues inside the mother's body. In this way, females gain some time to
      search for less risky oviposition sites.

PMID- 16955288
TI  - The sensitivity of ecosystem carbon exchange to seasonal precipitation and woody
      plant encroachment.
AB  - Ongoing, widespread increases in woody plant abundance in historical grasslands
      and savannas (woody encroachment) likely will interact with future precipitation
      variability to influence seasonal patterns of carbon cycling in water-limited
      regions. To characterize the effects of woody encroachment on the sensitivity of
      ecosystem carbon exchange to seasonal rainfall in a semi-arid riparian setting we
      used flux-duration analysis to compare 2003-growing season NEE data from a
      riparian grassland and shrubland. Though less seasonally variable than the
      grassland, shrubland NEE was more responsive to monsoon rains than anticipated.
      During the 2004-growing season we measured leaf gas exchange and collected leaf
      tissue for delta(13)C and nitrogen content analysis periodically among three size
      classes of the dominant woody-plant, Prosopis velutina and the dominant
      understory species, Sporobolus wrightii, a C(4) bunchgrass, present at the
      shrubland. We observed size-class and plant functional type independent patterns
      of seasonal plant performance consistent with greater-than-anticipated
      sensitivity of NEE in the shrubland. This research highlights the complex
      interaction between growing-season precipitation, plant-available alluvial
      groundwater and woody plant abundance governing ecosystem carbon balance in this
      semi-arid watershed.

PMID- 16955290
TI  - Effects of partial throughfall exclusion on the phenology of Coussarea racemosa
      (Rubiaceae) in an east-central Amazon rainforest.
AB  - Severe droughts may alter the reproductive phenology of tropical tree species,
      but our understanding of these effects has been hampered by confounded variation
      in drought, light and other factors during natural drought events. We used a
      large-scale experimental reduction of throughfall in an eastern-central Amazon
      forest to study the phenological response to drought of an abundant subcanopy
      tree, Coussarea racemosa. We hypothesized that drought would alter the production
      and the timing of reproduction, as well as the number of viable fruits. The study
      system comprised two 1-ha plots in the Tapajos National Forest, Para, Brazil: a
      dry plot where 50% of incoming precipitation (80% throughfall) was diverted from
      the soil during the six-month wet season beginning in January 2000, and a wet
      plot that received natural rainfall inputs. Fruit production of C. racemosa was
      quantified every 15 days using 100 litter traps (0.5 m(2)) in each plot. The
      production of new leaves and flowers was recorded monthly for C. racemosa
      individuals. Soil water, pre-dawn leaf water potential and solar radiation were
      measured to help interpret phenological patterns. Over the approximately 3.5-year
      period (April 2000 through December 2003), total fruit production remained
      similar between plots, declining by 12%. In 2003, production was four times
      higher in both plots than in previous years. In the dry plot, fruit fall shifted
      40 and 60 days later into the dry season in 2002 and 2003, respectively. Total
      fruit fall dry mass production was variable across the study period. Foliage and
      flower production coincided with peak irradiance early in the dry season until
      delays in flowering appeared in the dry plot in 2002 and 2003. Plant water
      stress, through its influence on leaf developmental processes and, perhaps,
      inhibition of photosynthesis, appears to have altered both the timing of fruit
      fall and the quality and number of seeds produced.

PMID- 16955291
TI  - Reliability of a 5 x 6-s maximal cycling repeated-sprint test in trained female
      team-sport athletes.
AB  - The present study examined the reliability of work and power measures during a 5
      x 6-s cycle ergometer test of repeated-sprint ability. Nine, well-trained, female
      soccer players performed five, 5 x 6-s repeated-sprint tests on a front-access
      cycle ergometer on separate days. Sprints were separated by 24 s of active
      recovery. Absolute measures of total work done (W (tot)), total peak power
      (PP(tot)), work done during sprint 1 (W (1)) and peak power output during sprint
      1 (PP(1)) were recorded. Decrement scores in work done (W (dec)) and peak power
      output (PP(dec)), and fatigue indices for work done (FI( W )) and peak power (FI(
      P )), were calculated. Significant improvements in all of the work and power
      measures were observed between trial 1 and subsequent trials (P < 0.05), but no
      significant differences were identified between trials 2, 3, 4 and 5. The same
      was true for increases in the decrement scores. The coefficient of variation (CV)
      was established to reflect within-subject reproducibility for each variable. The
      CV was significantly improved by the third trial for work done (W (tot) CV:
      trials 1-2 = 5.5%; trials 3-4 = 2.8%), peak power (PP(tot) CV: trials 1-2 = 5.1%;
      trials 3-4 = 2.7%) and performance decrement scores (P < 0.05). The standard
      error of measurement (SEM) and intraclass correlation coefficient (ICC) were also
      calculated for each variable and expressed within 95% confidence intervals. It
      was concluded that two familiarisation trials are optimal for collecting reliable
      data from a 5 x 6-s repeated-sprint cycling test. Furthermore, due to the large
      variation around performance decrement it was suggested that decrement scores
      ought to be interpreted with caution.

PMID- 16955293
TI  - [Patient-controlled analgesia (PCA) in outpatients with cancer pain. Analysis of
      1,692 treatment days].
AB  - INTRODUCTION: In the home-care setting, cancer pain patients in need of
      parenteral analgesia have to be switched to patient-controlled analgesia using
      portable pumps. But there is a paucity on data on the logistic requirements or
      the success rate of such a cost-intensive therapy performed by specialized home
      care services. METHODS: In a retrospective study we analyzed data on care
      intensity, logistics and outcome of 46 consecutive palliative cancer patients
      with patient-controlled analgesia (PCA) in a home-care setting. RESULTS: On days
      1, 2, and 3 of PCA the switch to parenteral analgesia resulted in a significant
      increase of the median daily opioid dose in comparison to the dose just prior to
      PCA. Concurrently, pain scores were significantly reduced. The median duration of
      PCA was 25 days (range 2-189 days). On average, each patient was seen by the home
      care team every 7.4 days. The median duration of the home visits was 60 min
      (range, 10-190 min). Of the visits 20% were unscheduled, most of these visits
      being due to problems regarding analgesia. Most patients died at home.
      Insufficient analgesia required prefinal hospitalization in only a single case.
      CONCLUSION: If the indications are correct, intravenous PCA for palliative cancer
      pain patients results in higher opioid consumption and better pain control. Home
      care PCA requires a lot of human and financial resources, but pain-related
      hospitalization can be prevented.

PMID- 16955294
TI  - [Acetylsalicylic acid in self-medication of migraine. A pharmacy-based
      observational study].
AB  - BACKGROUND: The aim of the study was to investigate the efficacy and tolerability
      of acetylsalicylic acid in the treatment of acute migraine attacks by self
      medication under daily life conditions when bought in a pharmacy and also the
      ability of patients to self-diagnose correctly. METHODS: A total of 296 patients
      were recruited from 156 pharmacies and recorded up to 3 migraine attacks.
      Following an advisory discussion the pharmacists gave a questionnaire to persons
      who had purchased acetylsalicylic acid (Aspirin Migraine) in the pharmacy to
      treat migraine. A total of 578 questionnaires containing 36 questions about
      demographic details, headache phenotype, medical history, efficacy over 2 h and
      tolerability of the preparation were analyzed. RESULTS: The IHS criteria (1988)
      for migraine were identified correctly by 92.7% of the patients. In 66.3% of the
      attacks, the intensity of the headache was reported as severe. In 60% of the
      documented attacks, a decrease from severe or moderate to mild or no headache was
      recorded after medication, and freedom from headache was achieved in 35.8%. The
      effect was reproducible over 3 migraine attacks. Nausea, photophobia and
      phonophobia were reduced by 71-86% compared to the baseline level. Side-effects
      were reported twice as often by the participants in response to closed questions
      than to open questions (16.6 vs. 8.3%). CONCLUSION: A high percentage of migraine
      patients are capable of diagnosing their condition themselves when they seek
      advice in a pharmacy. The data on efficacy confirm the results from controlled
      clinical studies. The same parameters as those used in controlled clinical
      studies can also be recorded in pharmacy-based observational studies, therefore,
      the safety and tolerability of the medication can be recorded under real
      conditions.

PMID- 16955295
TI  - [Headache patients in routine clinical practice. When are additional instrumental
      examinations indicated?].
AB  - In routine clinical practice, the question whether instrumental examinations of
      patients with headaches should be carried out, is not always easy. If secondary
      headaches are suspected, with atypical presentation and focal neurological signs
      or symptoms, magnetic resonance imaging (MRI) may be indicated. In primary
      headaches, such as migraine, tension headache or trigemino-autonomic headaches,
      no further diagnostic procedures are warranted, as long as the clinical
      presentation is typical (i.e. corresponds to the International Headache Society
      guidelines) and neurological examination is normal. This article reviews the
      evidence from the literature and recommendations of European and American task
      forces regarding the use of instrumental examinations in case of non-acute
      primary headache.

PMID- 16955296
TI  - [Pain therapy in addicted patients].
AB  - Each individual is entitled to an adequate and sufficient pain therapy. However,
      only a few studies have examined the peculiarities of pain management in drug
      dependent or formerly addicted patients. Any addiction is disadvantageous for a
      successful pain therapy, since some of the prescribed drugs may themselves cause
      addiction. Drug-dependent patients are often tolerant to opioids. Additionally,
      there is a risk of iatrogenic pain becoming chronic due to disregard for already
      known risk factors and comorbidities. However, a history of addiction should not
      prevent sufficient pain therapy, especially since there is no risk of addiction
      when the pain therapy employed is adequate for the pathophysiology involved.
      There are adequate pain therapies for addicted patients. The best results are
      achieved by taking into account the physiological and psychological peculiarities
      of drug-dependent patients. Importantly, this should be combined with a variety
      of different, optimized, multimodal therapeutic regimes, as well as with an
      interdisciplinary approach.

PMID- 16955297
TI  - Phase II study of interleukin-2 and 13-cis-retinoic acid as maintenance therapy
      in metastatic colorectal cancer.
AB  - PURPOSE: We have previously shown that low-dose interleukin-2 (IL-2) and 13-cis
      retinoic acid (13-cis-RA) improved lymphocyte and natural killer (NK) cell count
      of patients with advanced tumors showing a clinical benefit from chemotherapy.
      The primary endpoint of this study was to ask whether IL-2 and 13-cis-RA improved
      (> or =30%) lymphocyte and NK cell count in patients with metastatic colorectal
      cancer (MCRC) that had a clinical benefit from induction chemotherapy. Secondary
      endpoint was the evaluation of toxicity, progression-free survival (PFS), and
      overall survival (OS). PATIENTS AND METHODS: Forty patients with MCRC, showing a
      clinical benefit from chemotherapy, were treated with subcutaneous low-dose IL-2
      (1.8 x 10(6) IU) and oral 13-cis-RA (0.5 mg/kg) in order to maintain responses
      and improve survival through the increase of lymphocyte and NK cells. The
      biological parameters and the clinical outcome of these patients were compared
      with those of a control group of patients (80) with a similar disease status,
      including clinical benefit from chemotherapy. RESULTS: The most common adverse
      events were mild cutaneous skin rash and fever. After 4 months and 2 years of
      biotherapy, a statistically significant improvement was observed in lymphocyte
      and number of NK cells with respect to baseline values and to controls. After a
      median follow-up of 36 months, median PFS was 27.8 months, while median OS was
      52.9 months. CONCLUSION: These data show that maintenance immunotherapy with low
      dose IL-2 and oral 13-cis-RA in patients with MCRC showing a clinical benefit
      from chemotherapy is feasible, has a low toxicity profile, improves lymphocyte
      and NK cell count. An improvement in the expected PFS and OS was also observed. A
      randomized trial is warranted.

PMID- 16955298
TI  - Anatomic variations of the shape of the menisci: a neonatal cadaver study.
AB  - Meniscal injuries in children and adolescents are being seen with increased
      frequency. The menisci are two crescentic lamellae whose functions are to deepen
      the articular surfaces of the tibial plateu for reception of the condyles of the
      femur. In our study, our aim is to determine the variations of the shapes and
      attachments of the menisci in newborns. This study was performed on 11 neonatal
      cadavers, 22 knee joints that were obtained from the anatomy laboratory. The
      variations of the shape of the menisci were noted. We found that 77% of the
      lateral menisci were discoid. This percent is higher than the previously reported
      percents of the lateral discoid menisci. The different shapes of the menisci were
      determined as horse shoe, sickle, sided U, sided V and C shaped. We did not
      determine any discoid medial menisci. We believe that our study will provide
      support to the neonatal anatomy of the knee, concerning with the surgical
      procedures and arthroscopy of the knee joint.

PMID- 16955299
TI  - Early active extension after anterior cruciate ligament reconstruction does not
      result in increased laxity of the knee.
AB  - If permission of full active and passive extension immediately after an anterior
      cruciate ligament (ACL) reconstruction will increase the post-operative laxity of
      the knee has been a subject of discussion. We investigated whether a post
      operative rehabilitation protocol including active and passive extension without
      any restrictions in extension immediately after an ACL reconstruction would
      increase the post-operative anterior-posterior knee laxity (A-P laxity). Our
      hypothesis was that full active and passive extension immediately after an ACL
      reconstruction would have no effect on the A-P laxity and clinical results up to
      2 years after the operation. Twenty-two consecutive patients (14 men, 8 women,
      median age 21 years, range 17-41) were included. All the patients had a
      unilateral ACL rupture and no other ligament injuries or any other history of
      previous knee injuries. The surgical procedure was identical in all patients and
      one experienced surgeon operated on all the patients, using the bone-patellar
      tendon-bone autograft. The post-operative rehabilitation programme was identical
      in both groups, except for extension training during the first 4 weeks post
      operatively. The patients were randomly allocated to post-operative
      rehabilitation programmes either allowing (Group A, n=11) or not allowing [Group
      B (30 to -10 degrees ), n=11] full active and passive extension immediately after
      the operation. They were evaluated pre-operatively and at 6 months and 2 years
      after the reconstruction. To evaluate the A-P knee laxity, radiostereometric
      analysis (RSA) and KT-1000 arthrometer (KT-1000) measurements were used, range of
      motion, Lysholm score, Tegner activity level, the International Knee
      Documentation Committee (IKDC) evaluation system and one-leg-hop test quotient
      were used. Pre-operatively, the RSA measurements revealed side-to-side
      differences in Group A of 8.6 mm (2.3-15.4), median (range) and in Group B of 7.2
      mm (2.2-17.4) (n.s.). The corresponding KT-1000 values were for Group A, 2.0 mm
      (0-8.0) and Group B, 4.0 mm (0-10.0) (n.s.). At 2 years, the differences between
      the two groups were minimal, regardless of the method that had been used. The RSA
      measurements in Group A were 2.7 mm (0-10.7) and in Group B 2.8 (-1.8 to 9.5).
      The KT-1000 values were for Group A, 1.0 mm (-1.5 to 3.5), and for Group B, 0.5
      mm (-1.0 to 4.0), without any significant differences between the groups. Nor did
      the Lysholm score, Tegner activity level, IKDC or one-leg-hop test differ. Early
      active and passive extension training, without any restrictions in extension,
      immediately after an ACL reconstruction using bone-patellar tendon-bone graft did
      not increase post-operative knee laxity up to 2 years after the ACL
      reconstruction.

PMID- 16955300
TI  - Liquid chromatography-electrospray ionization mass spectrometry for simultaneous
      detection of mtDNA length and nucleotide polymorphisms.
AB  - We demonstrate the applicability of ion-pair reversed-phase high-performance
      liquid chromatography-electrospray ionization time-of-flight mass spectrometry
      (ICEMS) for the simultaneous characterization of length and nucleotide
      polymorphisms. Two sections within the first (HVS-I) and second (HVS-II)
      hypervariable segments of the mitochondrial (mt)DNA control region were selected
      as targets, both containing poly-cytosine (C) tracts, which display length
      heteroplasmy at a substantial frequency in the population. The two mtDNA sections
      were simultaneously amplified and analyzed by ICEMS in 90 maternally unrelated
      mother-offspring pairs from Austria. The findings were confirmed by direct
      sequencing of the polymerase chain reaction products. For the detailed
      characterization of present-length heteroplasmic variants, the results retrieved
      through ICEMS were more informative compared with those derived from direct
      sequencing. Hence, ICEMS represents an interesting option for successful
      application in forensic science.

PMID- 16955301
TI  - The use of LigaSure in patients with hyperthyroidism.
AB  - BACKGROUND: Thyroidectomies of hyperthyroidic patients are known to be more blood
      spattered than the operations performed for euthyroid nodular diseases and
      require careful hemostasis. Our purpose was to evaluate the efficacy of the use
      of LigaSure in patients with hyperthyroidism. MATERIALS AND METHODS: Between
      January 2004 and October 2005, 100 patients underwent total or near-total
      thyroidectomy. Bipolar vessel ligation system (LigaSure) was the choice of
      modality for hemostasis in half of these patients, and the conventional suture
      ligation technique was used for the rest. The following data were evaluated non
      randomized and prospectively in this study: patients demographics, thyroid
      pathology, operative duration, presence of complications, and the duration of the
      hospital stay. Comparisons of the data were evaluated by the Wilcoxon and chi
      square tests. RESULTS: Among the patients of the LigaSure group, 14 patients were
      detected to have hyperthyroidism (seven patients with Graves' disease and another
      seven patients with multinodular toxic goiter), while 36 patients were found to
      be euthyroidic. The durations of the operation time and of the hospital stay of
      the patients in the LigaSure group were significantly lower than the conventional
      thyroidectomy group (p<0.05). The complication rates of the LigaSure and
      conventional thyroidectomy groups were 4 and 6%, respectively (p>0.05).
      CONCLUSIONS: The use of LigaSure as an operative technique in the treatment of
      Graves' disease and toxic goiter is a safe and effective modality that provides a
      shorter hospital stay and a shorter operation time as well.

PMID- 16955302
TI  - Supervised surgical trainees perform thyroid surgery for Graves' disease safely.
AB  - BACKGROUND: There is little information about the effect of operative experience
      and supervision of trainees on long-term outcomes after thyroid resection for
      Graves' disease (GD). The aim of this study was to compare the morbidity rate
      after thyroid resection performed by trainees vs consultant surgeons. METHODS:
      Based on a cross-sectional design analysis with a median follow-up of 96 months
      (range, 12-216 months), long-term outcomes for 111 patients operated on by
      consultants were compared with those of 42 patients operated on by supervised
      trainees in an academic teaching hospital between 1987 and 2002. RESULTS: Of the
      111 patients operated on by the consultants, there were 25 (21.6%) cases of
      transient and 12 (10.8%) cases of permanent hypocalcemia and 10 (9.0%) cases of
      transient and 1 (0.9%) case of permanent recurrent laryngeal nerve (RLN) palsy.
      Of the 42 patients operated upon by the supervised trainees, there were 8 (21.4%)
      cases of transient and no permanent hypocalcemia, 3 (7.1%) cases of transient,
      and 1 (2.3%) case of permanent RLN palsy. Permanent complication rate of the
      entire group was low, and the grade of the primary surgeon made no difference in
      the occurrence of complications (P>0.05). CONCLUSION: Supervised trainees can
      perform thyroid surgery for GD safely if a standardized surgical teaching program
      is available.

PMID- 16955303
TI  - [Specific immunotherapy].

PMID- 16955304
TI  - [Mechanisms of specific immunotherapy].
AB  - Specific immunotherapy (SIT) is a well-established and clinically effective
      treatment for allergic rhinitis and bronchial asthma. The immunological
      mechanisms of the subcutaneously applied immunotherapy have been partially
      elucidated over the past several years but are not completely understood. This
      report summarizes the immunological and immunoregulatory changes during SIT of
      wasp venom allergic patients. The induction of IL-10-producing regulatory T cells
      is described.

PMID- 16955305
TI  - [Surgical procedure in thoracic trauma].

PMID- 16955306
TI  - [Chest injury. Part II: Management of specific injuries].
AB  - Significant injuries to the thorax comprise pneumothorax, rib fractures, lung
      contusion, cardiac contusion, aortic laceration, ruptured diaphragm, and the very
      rare injuries to the tracheo-bronchial tree and the esophagus. A surgeon dealing
      with chest trauma patients needs to be familiar with the indications for and
      execution of chest tube insertion for thoracic drainage, pericardial puncture,
      and thoracoscopy and thoracotomy. Interventional techniques are gaining
      increasing acceptance in the management of major vascular injuries. The vast
      majority of patients with chest injury do not need an operative intervention, but
      it is necessary to place a thoracic drain in 10-15% of cases or to perform in a
      much lower proportion a pericardial puncture or a thoracotomy.

PMID- 16955307
TI  - Secretagogin, a novel neuroendocrine marker, has a distinct expression pattern
      from chromogranin A.
AB  - Preliminary data suggest that secretagogin (SCGN), a calcium-binding protein
      identified from our previous proteomics study of colorectal cancers, is a
      potentially useful neuroendocrine marker. In this study, we further analyzed SCGN
      expression in normal and tumor tissues from various organ sites compared with
      three other conventional neuroendocrine markers [chromogranin A (CgA), neuron
      specific enolase, and synaptophysin]. We found strong SCGN staining in most
      normal neuroendocrine tissues except in the adrenal cortex. SCGN expression was
      identified in 140 out of 213 neuroendocrine tumors and 12 conventional carcinomas
      with neuroendocrine differentiation. In a subset of neuroendocrine tumors, such
      as gastric neuroendocrine cancers and typical carcinoid tumors of rectum and
      ovary, SCGN showed strong staining while CgA expression was often negative. It is
      intriguing to note that SCGN staining was positive in 26 out of 31 small cell
      lung cancers, more frequently than the other three markers. We conclude that SCGN
      is a novel neuroendocrine marker that may be useful in routine surgical pathology
      practice.

PMID- 16955308
TI  - The hepatitis C virus NS5A protein and response to interferon alpha: mutational
      analyses in patients with chronic HCV genotype 3a infection from India.
AB  - The hepatitis C virus (HCV) non-structural (NS)5A protein is linked to interferon
      alpha resistance in vitro and higher numbers of NS5A amino acid (aa) variations
      in HCV 1a/b isolates are associated with virologic response to interferon alpha
      based therapy in vivo. Here, we aimed to study NS5A aa variations in Indian
      patients undergoing interferon alpha/ribavirin treatment infected with HCV 3a.
      The NS5A region [aa 2194-2401, comprising interferon sensitivity determining
      region, protein kinase resource (PKR) binding domain, V3 region] was sequenced
      from pre-treatment sera of 24 patients with HCV 3a infection. Mean number and
      physicochemical properties of aa variations (conserved vs. non-conserved) were
      assessed. Additionally, published NS5A sequences [NS5A region (n = 61), PKR
      binding domain (n = 111)] of characterized HCV 3a isolates were analyzed. The
      mean number of NS5A aa variations was not correlated with treatment response in
      our cohort. When all available NS5A sequences were included, a higher number of
      non-conserved aa variations within PKR binding domain and an extended V3 region
      of NS5A was associated with virologic response (P = 0.004 and 0.05,
      respectively). Mutational analyses of a large number of NS5A sequences suggest,
      that a higher number of non-conserved aa variations within the PKR binding domain
      and the extended V3 region is correlated with virologic response in HCV 3a
      infected patients.

PMID- 16955310
TI  - Alterations in calcium homeostasis reduce membrane excitability in amphibian
      skeletal muscle.
AB  - The effects of alterations in intracellular calcium homeostasis on surface
      membrane excitability were investigated in resting Rana temporaria sartorius
      muscle. This was prompted by initial results from a fatiguing stimulation
      protocol study that demonstrated a fibre subpopulation in which action potential
      generation in response to a standard 1.5 V electrical stimulus failed despite
      mean membrane potentials [E (m), -69+/-2.3 mV (n=14)] compatible with spike
      firing in a control set of quiescent muscle fibres. Intracellular micro-electrode
      recordings showed a similar reversible loss of excitability, attributable to an
      increased threshold, despite only small (7.1+/-1.8 mV) positive changes in E (m)
      after approximately 60-min exposures to nominally 0 Ca(2+) Ringer solutions in
      which Ca(2+) was replaced by Mg(2+). This effect was not reproduced by addition
      of Mg(2+) to the Ringer solution and persisted under conditions of Cl(-)
      deprivation. The effects of three pharmacological agents, cyclopiazonic acid
      (CPA), caffeine and 4-chloro-m-cresol (4-CmC), each known to deplete store Ca(2+)
      and increase cytosolic Ca(2+) through contrasting mechanisms without influencing
      E (m), were then investigated. All three agents produced a more rapid, but
      nevertheless still reversible, loss of membrane excitability than in 0 Ca(2+)
      Ringer solution alone. This reduction in membrane excitability persisted in
      fibres studied in solutions containing a normal [Ca(2+)] following prior
      depletion of store Ca(2+) using CPA- and 4-CmC-containing solutions. These novel
      findings suggest that sarcoplasmic reticulum Ca(2+) content profoundly influences
      surface membrane excitability, thereby providing a potential mechanism by which
      spike firing fails in well-polarised fibres during fatigue.

PMID- 16955311
TI  - Evidence for common structural determinants of activation and inactivation in T
      type Ca2+ channels.
AB  - One of the most distinctive features of T-type Ca(2+) channels is their fast
      inactivation. Recent structure-function studies indicate that the rate of
      macroscopic inactivation of these channels is influenced by several structural
      components, including intracellular linkers, transmembrane segments, and pore
      loops. The macroscopic inactivation of T-type channels is partially coupled to
      activation. It is therefore possible that changes in the rate of macroscopic
      inactivation after alteration in the structure of these channels might actually
      result from changes in activation kinetics. In this study, we use kinetic
      simulations to illustrate how the alteration of the rate of channel activation
      may lead to changes in the rate of macroscopic inactivation. By examining data
      pooled from several structure-function studies we demonstrate that gating
      modifications induced by alteration in the channel structure unveils a
      correlation between the time constants of macroscopic inactivation and
      activation. This analysis underscores the relevance of considering the
      inactivation-activation coupling when analyzing the structural determinants of T
      type channel inactivation. Furthermore, we demonstrate that slow-inactivating
      mutants, with modifications in the IIIS6 segment and the proximal C terminus,
      display significant alterations in the voltage dependencies of activation and
      deactivation with respect to the wild type channel Ca(V)3.1. Our results indicate
      that common structures, most likely the S6 transmembrane segments, are involved
      in the conformational changes occurring during both channel activation and
      inactivation.

PMID- 16955313
TI  - [Central and peripheral deafferent pain: therapy with repetitive transcranial
      magnetic stimulation].
AB  - BACKGROUND: This study evaluates the effects of repeated sessions of low- and
      high-frequency repetitive transcranial magnetic stimulation (rTMS) over the
      primary motor cortex on central and phantom limb pain. METHODS: Twenty seven
      patients with central (n=13) and phantom limb (n=14) pain participated in a
      blind, randomised placebo-controlled study comparing the effect of 1-Hz and 5-Hz
      rTMS with sham stimulation. Each treatment block consisted of a 5-day baseline
      phase, a 5-day therapy phase, and an 18-day washout phase. In the therapy phase,
      500 stimuli were applied in the particular frequency at about the same time on
      each day. RESULTS: A reduction in pain immediately after stimulation was observed
      in all therapy groups. This effect was similar for all treatment conditions,
      including sham stimulation. No significant long-term effects of rTMS on pain
      intensity or mood were observed. CONCLUSION: At present, rTMS can not be
      recommended as a standard therapy for central and phantom limb pain.

PMID- 16955314
TI  - [Risk assessment of sex offenders in a German-speaking sample. Applicability of
      PCL-SV, HCR-20+3, and SVR-20].
AB  - Regarding the relatively high relapse rates of sex offenders, an increasing need
      for forensic prognosis reports, doubts about their validity, and a continued lack
      of qualified forensic experts makes the supposedly simple application of
      instruments such as the Psychopathy Check List Screening Version (PCL-SV), HCR
      20+3, or the Sexual Violence Risk 20 (SVR-20) very tempting. Those tools supply
      numeric values for quantifying assumed risk and have begun appearing more
      frequently in forensic reports. Their use for specific collectives without prior
      examination of accuracy, admissibility, and accountability may lead to serious
      mistakes and risks. This study by the Forensic Department of the Psychiatric
      University Hospital in Basel, Switzerland, is part of a larger cohort study on
      forensic risk assessment. It investigates among others the differential
      indication for PCL-SV, HCR-20+3, and SVR-20. In the present study, 64 sex
      offenders were retrospectively rated with these three instruments based on their
      respective reports for prior risk assessment, including criminal reports. Those
      ratings were then compared with prior results from the Structured Risk Assessment
      of Basel, as performed by the experts. Results of this study confirm the utility
      of PCL-SV, HCR-20+3 and SVR-20 in a German-speaking sample of sex offenders
      primarily as a scientific instrument. Beyond that, these instruments may also be
      used literally as a checklist. Their use for risk quantification should be
      limited primarily to the subgroup of antisocial and physically aggressive sex
      offenders.

PMID- 16955315
TI  - [Agitation and gamma-hydroxybutyrate].
AB  - Agitation is a symptom in various disorders. Gamma-hydroxybutyrate (GHB) is often
      abused because of its stimulating effects. Side effects comprise loss of
      consciousness, coma, and agitated states. We present a 50-year-old patient with
      repeated GHB intoxications and abstinent alcohol dependency and a video document
      showing an agitated state. Diagnostic workup is discussed considering the
      relevant literature on this topic. Intoxication and dependence on GHB are
      important entities in the contexts of neurology and psychiatry.

PMID- 16955316
TI  - Direct extraction of curvature-based metric shape from stereo by view-modulated
      receptive fields.
AB  - Any computation of metric surface structure from horizontal disparities depends
      on the viewing geometry, and analysing this dependence allows us to narrow down
      the choice of viable schemes. For example, all depth-based or slant-based schemes
      (i.e. nearly all existing models) are found to be unrealistically sensitive to
      natural errors in vergence. Curvature-based schemes avoid these problems and
      require only moderate, more robust view-dependent corrections to yield local
      object shape, without any depth coding. This fits the fact that humans are
      strikingly insensitive to global depth but accurate in discriminating surface
      curvature. The latter also excludes coding only affine structure. In view of new
      adaptation results, our goal becomes to directly extract retinotopic fields of
      metric surface curvatures (i.e. avoiding intermediate disparity curvature). To
      find a robust neural realisation, we combine new exact analysis with basic neural
      and psychophysical constraints. Systematic, step-by-step 'design' leads to neural
      operators which employ a novel family of 'dynamic' receptive fields (RFs), tuned
      to specific (bi-)local disparity structure. The required RF family is dictated by
      the non-Euclidean geometry that we identify as inherent in cyclopean vision. The
      dynamic RF-subfield patterns are controlled via gain modulation by binocular
      vergence and version, and parameterised by a cell-specific tuning to slant. Our
      full characterisation of the neural operators invites a range of new
      neurophysiological tests. Regarding shape perception, the model inverts widely
      accepted interpretations: It predicts the various types of errors that have often
      been mistaken for evidence against metric shape extraction.

PMID- 16955317
TI  - [My recollections of DGU (German Society of Urology)].

PMID- 16955318
TI  - [Introductory address of the president of the Austrian Society of Urology and
      Andrology].

PMID- 16955319
TI  - [13 years Greek-German Society of Urology].

PMID- 16955320
TI  - Centennial celebration of the German Society of Urology (DGU).

PMID- 16955321
TI  - My congratulations to the German Society of Urology!

PMID- 16955322
TI  - To the German Society of Urology - centennial celebration.

PMID- 16955323
TI  - Reflections on a successful relationship.

PMID- 16955324
TI  - A lifelong human and professional camaraderie.

PMID- 16955325
TI  - [The common future of urology and the pharmaceutical industry].

PMID- 16955326
TI  - [Yesterday, today and tomorrow: urology and the pharmaceutical industry:
      successful team work for the benefit of the patient].

PMID- 16955327
TI  - Male and female effects on sperm precedence in the giant sperm species Drosophila
      bifurca.
AB  - Sperm competition is expected to be a driving force in sexual selection. In
      internally fertilized organisms, it occurs when ejaculates from more than one
      male are present simultaneously within the female's reproductive tract. It has
      been suggested that greater sperm size may improve the competitive ability of
      sperm, but studies provide contradictory results depending on the species. More
      recently, the role of females in the evolution of sperm morphology has been
      pointed out. We investigate here the male and female effects that influence sperm
      precedence in the giant sperm species, Drosophila bifurca Patterson & Wheeler.
      Females were mated with two successive males, and the paternity outcomes for both
      males were analyzed after determining sperm transfer and storage. We found very
      high values of last male sperm precedence, suggesting a strong interaction
      between rival sperm. However, the data also indicate high frequencies of removal
      of the sperm of the first male from the female reproductive tract prior to any
      interaction with the second male. This implies that successful paternity depends
      mainly on successful sperm storage. Knowing what happens to the sperm within
      females appears to be a prerequisite for disentangling post-copulatory sexual
      interactions between males and females.

PMID- 16955328
TI  - A statistical model for dissecting genomic imprinting through genetic mapping.
AB  - As a result of nonequivalent genetic contribution of maternal and paternal
      genomes to offsprings, genomic imprinting or called parent-of-origin effect, has
      been broadly identified in plants, animals and humans. Its role in shaping
      organism's development has been unanimously recognized. However, statistical
      methods for identifying imprinted quantitative trait loci (iQTL) and estimating
      the imprinted effect have not been well developed. In this article, we propose an
      efficient statistical procedure for genomewide estimating and testing the effects
      of significant iQTL underlying the quantitative variation of interested traits.
      The developed model can be applied to two different genetic cross designs,
      backcross and F(2) families derived from inbred lines. The proposed procedure is
      built within the maximum likelihood framework and implemented with the EM
      algorithm. Extensive simulation studies show that the proposed model is well
      performed in a variety of situations. To demonstrate the usefulness of the
      proposed approach, we apply the model to a published data in an F(2) family
      derived from LG/S and SM/S mouse stains. Two partially maternal imprinting iQTL
      are identified which regulate the growth of body weight. Our approach provides a
      testable framework for identifying and estimating iQTL involved in the genetic
      control of complex traits.

PMID- 16955329
TI  - Resolving the genetic basis of invasiveness and predicting invasions.
AB  - Considerable effort has been invested in determining traits underlying
      invasiveness. Yet, identifying a set of traits that commonly confers invasiveness
      in a range of species has proven elusive, and almost nothing is known about
      genetic loci affecting invasive success. Incorporating genetic model organisms
      into ecologically relevant studies is one promising avenue to begin dissecting
      the genetic underpinnings of invasiveness. Molecular biologists are rapidly
      characterizing genes mediating developmental responses to diverse environmental
      cues, i.e., genes for plasticity, as well as to environmental factors likely to
      impose strong selection on invading species, e.g., resistance to herbivores and
      competitors, coordination of life-history events with seasonal changes, and
      physiological tolerance of heat, drought, or cold. Here, we give an overview of
      molecular genetic tools increasingly used to characterize the genetic basis of
      adaptation and that may be used to begin identifying genetic mechanisms of
      invasiveness. Given the divergent traits that affect invasiveness, "invasiveness
      genes" common to many clades are unlikely, but the combination of developmental
      genetic advances with further evolutionary studies and modeling may provide a
      framework for identifying genes that account for invasiveness in related species.

PMID- 16955330
TI  - Hybridization and the colonization of novel habitats by annual sunflowers.
AB  - Although invasive plant species often have a hybrid ancestry, unambiguous
      evidence that hybridization has stimulated the evolution of invasive behaviors
      has been difficult to come by. Here, we briefly review how hybridization might
      contribute to the colonization of novel habitats, range expansions, and
      invasiveness and then describe work on hybrid sunflowers that forges a direct
      link between hybridization and ecological divergence. We first discuss the
      invasion of Texas by the common sunflower and show that the introgression of
      chromosomal segments from a locally adapted species may have facilitated range
      expansion. We then present evidence that the colonization of sand dune, desert
      floor, and salt marsh habitats by three hybrid sunflower species was made
      possible by selection on extreme or "transgressive" phenotypes generated by
      hybridization. This body of work corroborates earlier claims regarding the role
      of hybridization in adaptive evolution and provides an experimental and
      conceptual framework for ongoing studies in this area.

PMID- 16955331
TI  - Climatic selection on genes and traits after a 100 year-old invasion: a critical
      look at the temperate-tropical clines in Drosophila melanogaster from eastern
      Australia.
AB  - Drosophila melanogaster invaded Australia around 100 years ago, most likely
      through a northern invasion. The wide range of climatic conditions in eastern
      Australia across which D. melanogaster is now found provides an opportunity for
      researchers to identify traits and genes that are associated with climatic
      adaptation. Allozyme studies indicate clinal patterns for at least four loci
      including a strong linear cline in Adh and a non-linear cline in alpha-Gpdh.
      Inversion clines were initially established from cytological studies but have now
      been validated with larger sample sizes using molecular markers for breakpoints.
      Recent collections indicate that some genetic markers (Adh and In(3R)Payne) have
      changed over the last 20 years reflecting continuing evolution. Heritable clines
      have been established for quantitative traits including wing length/area, thorax
      length and cold and heat resistance. A cline in egg size independent of body size
      and a weak cline in competitive ability have also been established. Postulated
      clinal patterns for resistance to desiccation and starvation have not been
      supported by extensive sampling. Experiments under laboratory and semi-natural
      conditions have suggested selective factors generating clinal patterns,
      particularly for reproductive patterns over winter. Attempts are being made to
      link clinal variation in traits to specific genes using QTL analysis and the
      candidate locus approach, and to identify the genetic architecture of trait
      variation along the cline. This is proving difficult because of inversion
      polymorphisms that generate disequilibrium among genes. Substantial gaps still
      remain in linking clines to field selection and understanding the genetic and
      physiological basis of the adaptive shifts. However D. melanogaster populations
      in eastern Australia remain an excellent resource for understanding past and
      future evolutionary responses to climate change.

PMID- 16955333
TI  - Maternal expression increases the rate of bicoid evolution by relaxing selective
      constraint.
AB  - Population genetic theory predicts that maternal effect genes will evolve
      differently than genes expressed in both sexes because selection is only half as
      effective on autosomal genes expressed in one sex but not the other. Here, we use
      sequences of the tandem gene duplicates, bicoid (bcd) and zerknullt (zen), to
      test the prediction that, with similar coefficients of purifying selection, a
      maternal effect gene evolves more rapidly than a zygotic gene because of this
      reduction in selective constraint. We find that the maternal effect gene, bcd, is
      evolving more rapidly than zygotically expressed, zen, providing the first direct
      confirmation of this prediction of maternal effect theory from molecular
      evidence. Our results extend current explanations for the accelerated rate of bcd
      evolution by providing an evolutionary mechanism, relaxed selective constraint,
      that allows bcd the evolutionary flexibility to escape the typical functional
      constraints of early developmental genes. We discuss general implications of our
      findings for the role of maternal effect genes in early developmental patterning.

PMID- 16955334
TI  - Detecting natural selection on cis-regulatory DNA.
AB  - Changes in transcriptional regulation play an important role in the genetic basis
      for evolutionary change. Here I review a growing body of literature that seeks to
      determine the forces governing the non-coding regulatory sequences underlying
      these changes. I address the challenges present in studying natural selection
      without the familiar structure and regularity of protein-coding sequences, but
      show that most tests of neutrality that have been used for coding regions are
      applicable to non-coding regions, albeit with some caveats. While some
      experimental investment is necessary to identify heritable regulatory variation,
      the most basic inferences about selection require very little functional
      information. A growing body of research on cis-regulatory variation has uncovered
      all the forms of selection common to coding regions, in addition to novel forms
      of selection. An emerging pattern seems to be the ubiquity of local adaptation
      and balancing selection, possibly due to the greater freedom organisms have to
      fine-tune gene expression without changing protein function. It is clear from
      multiple single locus and whole genome studies of non-coding regulatory DNA that
      the effects of natural selection reach far beyond the start and stop codons.

PMID- 16955335
TI  - Structure of the genetic code suggested by the hydropathy correlation between
      anticodons and amino acid residues.
AB  - The correlation between hydropathies of anticodons and amino acids, detected by
      other authors utilizing scales of amino acid molecules in solution, was improved
      with the utilization of scales of amino acid residues in proteins. Three
      partitions were discerned in the correlation plot with the principal
      dinucleotides of anticodons (pDiN, excluding the wobble position). (a) The set of
      outliers of the correlation: Gly-CC, Pro-GG, Ser-GA and Ser-CU. The amino acids
      are consistently small, hydro-apathetic, stabilizers of protein N-ends, preferred
      in aperiodic protein conformations and belong to synthetases class II. The pDiN
      sequences are representative of the homogeneous sector (triplets NRR and NYY),
      distinguished from the mixed sector (triplets NRY and NYR), that depict a 70%
      correspondence to the synthetases class II and I, respectively. The triplet pairs
      proposed to be responsible for the coherence in the set of outliers are of the
      palindromic kind, where the lateral bases are the same, CCC: GGG and AGA: UCU.
      This suggests that UCU previously belonged to Ser, adding to other indications
      that the attribution of Arg to YCU was due to an expansion of the Arg-tRNA
      synthetase specificity. The other attributions produced two correlation sets. (b)
      One corresponds to the remaining pDiN of the homogeneous sector, containing both
      synthetase classes; its regression line overlapped the one formed by the
      remaining attributions to class II. (c) The other contains the pDiN of the mixed
      sector and produced steeper slopes, especially with the class I attributions. It
      is suggested that the correlation was established when the amino acid composition
      of the protein synthetases became progressively enriched and that the set of
      outliers were the earliest to have been fixed.

PMID- 16955332
TI  - Latitudinal clines for nucleotide polymorphisms in the Esterase 6 gene of
      Drosophila melanogaster.
AB  - Previous studies have found non-neutral patterns of nucleotide polymorphism in
      the promoter and coding regions of Est6 in D. melanogaster. Coding region
      polymorphism peaks around two closely linked replacement differences associated
      with the EST6-F/EST6-S allozyme polymorphism. The promoter contains two common,
      highly diverged haplotype groups, P1 and P7, that differentially affect Est6
      expression. Allozyme studies have also revealed latitudinal clines in EST6-F and
      EST6-S frequencies that recur across continents. Here we analyse nucleotide
      polymorphisms across the promoter and the region of peak coding sequence
      polymorphism in 10 Australian populations along a 25 degrees latitudinal gradient
      in order to examine the basis for the allozyme clines. As with the earlier
      studies, we find an excess of intermediate to high frequency variants in both the
      P1/P7 region and around the two EST6-F/EST6-S replacements in some populations.
      The two EST6-F/EST6-S replacement polymorphisms show latitudinal clines whereas
      the P1 and P7 groups of promoter haplotypes do not. However the strongest clines
      are for three co-segregating silent site polymorphisms in a 4 bp stretch at the
      3' end of the sequenced region. Monte Carlo simulations show that the clines for
      those three sites can explain all others in the data but none of the others can
      explain those three. Thus the allozyme clines may not reflect selection on either
      the P1/P7 polymorphism or the two replacements previously associated with the
      EST6-F/EST-S difference.

PMID- 16955336
TI  - Gilquiniid cestodes (Trypanorhyncha) from elasmobranch fishes off New Caledonia
      with descriptions of two new genera and a new species.
AB  - Cestodes were collected from deep-sea sharks caught off New Caledonia, South
      Pacific. Vittirhynchus squali n. g., n. sp. (Trypanorhyncha: Gilquiniidae) is
      described from the spiral valve of Squalus melanurus Fourmanoir & Rivaton. The
      new genus possesses four bothria and a typical heteroacanthous metabasal armature
      but has a file of three macrohooks forming a short chainette on the internal
      surface of the basal armature. Sagittirhynchus aculeatus n. g., n. sp., from the
      spiral valve of Centrophorus sp. (undescribed), also has four bothria and a
      typical heteroacanthous armature but lacks a distinctive basal swelling and has
      the final hooks of each principal row prominently enlarged. Gilquinia minor n.
      sp., from the spiral valve of Centrophorus sp. (undescribed), is distinguished by
      the presence of only five hooks per principal row compared with eight in
      congeners. Gilquinia sp. is reported from Squalus melanurus. G. robertsoni
      Beveridge, 1990 is reported from S. megalops (Macleay).

PMID- 16955337
TI  - The status of Acleotrema Johnston & Tiegs, 1922 and Heteroplectanum
      Rakotofiringa, Oliver & Lambert, 1987 (Monogenoidea: Diplectanidae), with the
      redescription of Acleotrema girellae Johnston & Tiegs, 1922.
AB  - Acleotrema Johnston & Tiegs, 1922 is resurrected and its diagnosis amended. A.
      girellae Johnston & Tiegs, 1922 is redescribed based on the lectotype from the
      Australian Museum (Sydney, Australia). A. kyphosi Yamaguti, 1968 is considered a
      junior synonym of A. girellae. Heteroplectanum Rakotofiringa, Oliver & Lambert,
      1987 is considered a junior synonym of Acleotrema. The nine species of the latter
      genus are transferred to Acleotrema as: A. diplobulbus (Yamaguti, 1968) n. comb.,
      A. nenue (Yamaguti, 1968) n. comb., A. spiculare (Yamaguti, 1968) n. comb., A.
      yamagutii (Oliver, 1983) n. comb., A. nenuoides (Rakotofiringa, Oliver & Lambert,
      1987) n. comb., A. parastromatei (Rakotofiringa, Oliver & Lambert, 1987) n.
      comb., A. serrulopenis (Rakotofiringa, Oliver & Lambert, 1987) n. comb., A.
      tamatavense (Rakotofiringa, Oliver & Lambert, 1987) n. comb. and A. oliveri (Leon
      Regagnon, Perez-Ponce de Leon & Garcia- Prieto, 1997) n. comb. An historical
      account of the species of Acleotrema is presented.

PMID- 16955338
TI  - Orectolobicestus n. g. (Cestoda: Tetraphyllidea), with the description of five
      new species and the transfer of Phyllobothrium chiloscyllii to the new genus.
AB  - ORECTOLOBICESTUS N. G. (CESTODA: Tetraphyllidea) is erected for six cestode
      species parasitising bamboo sharks (Orectolobiformes: Chiloscyllium). Members of
      this genus differ from all other phyllobothriid genera in possessing modified
      maisiform spinitriches on their distal bothridial surfaces. In addition, they are
      easily recognised in that they share the following unique combination of
      characters: their vitelline fields are interrupted by the ovary, their necks are
      scutellate, and their bothridia bear an apical sucker and marginal loculi. Five
      new species of Orectolobicestus are described, including O. tyleri n. sp. from
      Chiloscyllium punctatum off Borneo, O. lorettae n. sp. from C. cf. punctatum off
      Australia, O. mukahensis n. sp. and O. kelleyae n. sp. from C. indicum off
      Borneo, and O. randyi n.sp. from C. hasselti also from off Borneo. In addition,
      Phyllobothrium chiloscyllii Subhapradha, 1955 is transferred to the new genus. O.
      chiloscyllii (Subhapradha, 1955) n. comb. is readily distinguished from all five
      new species in its greater total length. In addition to a number of proglottid
      features, O. kelleyae n. sp. and O. randyi n. sp. clearly differ from the other
      three new species in their possession of trifid, rather than fully serrate,
      spinitriches on their proximal bothridial surfaces. The latter two species
      conspicuously differ from one another in total number of proglottids (11-21 vs 27
      38). O. tyleri n. sp. generally has fewer proglottids than O. lorrettae n. sp. (7
      17 vs 13-23) and, like O. mukahensis n. sp., possesses scutes that are spathate
      rather than elongate. O. tyleri n. sp. is readily distinguished from O.
      mukahensis n. sp. in its possession of fewer proglottids (7-17 vs. 19-29). The
      five new species of Orectolobicestus share derived bothridial microthrix features
      with Phyllobothrium squali Yamaguti, 1952, Thysanocephalum sp., Orygmatobothrium
      sp., Ruhnkecestus Caira & Durkin, 2006 and species of Paraorygmatobothrium
      Ruhnke, 1994. Among these taxa, Orectolobicestus most closely resembles
      Paraorygmatobothrium and Ruhnkecestus in its vitelline fields being interrupted
      by the ovary and the possession of a scutellate neck.

PMID- 16955340
TI  - A new species of Dicyemennea Whitman, 1883 (Phylum Dicyemida) from Sepia
      latimanus (Mollusca: Cephalopoda: Decapodidae) off Okinawa, Japan.
AB  - A new species of dicyemid mesozoan is described from a cuttlefish Sepia latimanus
      Quoy and Gaimard collected off Nago, Naha and Onnason, Okinawa Islands, Ryukyu
      Islands, Japan. Dicyemennea ryukyuense n. sp. is a large species that reaches
      about 5 mm in length. The vermiform stage is characterised by 23 peripheral
      cells, a conical calotte and an axial cell that extends to the base of the
      propolar cells. The infusoriform embryo consists of 37 cells; two nuclei are
      present in each urn cell and the refringent bodies are solid. In the type of
      reproductive strategy, rhombogens of D. ryukyuense form a small number of
      infusorigens and produce a relatively large number of gametes per infusorigen. In
      the family Dicyemidae, Dicyemennea Whitman, 1883 is the largest group after
      Dicyema von Kolliker, 1849. Other dicyemid species, including those belonging to
      Dicyema, were not detected. Dicyemids have never previously been detected in
      cephalopods living on corals and rocks off the Ryukyu Islands, even though they
      are benthonic in habitat. This is the first report of a dicyemid mesozoan from S.
      latimanus and also from off the Ryukyu Islands. S. latimanus inhabits coral
      reefs, often swimming over the coral but usually lying on the sandy bottom.
      Dicyemids cannot possibly infect cephalopods which live exclusively over coral
      and rock.

PMID- 16955339
TI  - Trypanosomes infecting cod Gadus morhua L. in the North Atlantic: a resurrection
      of Trypanosoma pleuronectidium Robertson, 1906 and delimitation of T. murmanense
      Nikitin, 1927 (emend.), with a review of other trypanosomes from North Atlantic
      and Mediterranean teleosts.
AB  - Trypanosomes were isolated from Atlantic cod Gadus morhua L. collected from
      several fjords in western Norway. Morphological studies showed that the 12
      infections studied represented a single species, identified as Trypanosoma
      pleuronectidium Robertson, 1906 which is resurrected and redescribed. This
      species is characterised by its body length (57.9 +/- 5.4 microm), nearly central
      nucleus (NI = 1.05 +/- 0.12) and relatively short post-kinetoplastic (PK) region
      (3.2 +/- 0.8 microm). T. pleuronectidium is transmitted by the leech Calliobdella
      nodulifera (Malm). T. murmanense Nikitin, 1927 (emend.) is delimited to a species
      transmitted by the leech Johanssonia arctica (Johansson). This species is
      separated from T. pleuronectidium by its attained body length, more anterior
      nucleus, presence of cytoplasmic refractive granules, adnuclear vacuoles and by a
      longer PK region. Partial SSU rDNA sequences of T. pleuronectidium and T.
      murmanense from Norway (1980 nt) diverged by 1.9%. The nominal North Atlantic and
      Mediterranean trypanosome species are reviewed, and T. flesi Lebailly, 1904, T.
      bothi Lebailly, 1905 and T. limandae Brumpt & Lebailly, 1904 are considered
      synonyms of T. platessae Lebailly, 1904. T. triglae senegalensis Ranque, 1973 is
      not considered conspecific with T. triglae Neumann, 1909, and consequently raised
      to species status as T. senegalense Ranque, 1973. Some other likely synonymies
      are discussed. In addition to T. pleuronectidium and T. murmanense, the following
      marine teleost trypanosomes are provisionally listed as valid species pending
      further study: T. callionymi Brumpt & Lebailly, 1904; T. cotti Brumpt & Lebailly,
      1904; T. delagei Brumpt & Lebailly, 1904; T. dorhni Yakimov, 1911; T. gobii
      Brumpt & Lebailly, 1904; T. laternae Lebailly, 1904; T. myoxocephali Fantham,
      Porter & Richardson, 1942; T. platessae Lebailly, 1904; T. scorpaenae Neumann,
      1909; T. soleae Laveran & Mesnil, 1901; T. triglae Neumann, 1909; and T. yakimovi
      Yakimov, 1911.

PMID- 16955341
TI  - Stem cell transplantation: potential impact on heart failure.
AB  - Cell transplantation is a promising new modality in treating damaged myocardium
      after myocardial infarction and in preventing postmyocardial infarction LV
      remodelling. Two strategies are plausible: the first uses adult tissue stem cells
      to replace the scar tissues and amend the lost myocardium, whilst the second
      strategy uses embryonic stem cells in an attempt to regenerate myocardium and/or
      blood vessels.

PMID- 16955344
TI  - The concepts of health and illness revisited.
AB  - Contemporary philosophy of health has been quite focused on the problem of
      determining the nature of the concepts of health, illness and disease from a
      scientific point of view. Some theorists claim and argue that these concepts are
      value-free and descriptive in the same sense as the concepts of atom, metal and
      rain are value-free and descriptive. To say that a person has a certain disease
      or that he or she is unhealthy is thus to objectively describe this person. On
      the other hand it certainly does not preclude an additional evaluation of the
      state of affairs as undesirable or bad. The basic scientific description and the
      evaluation are, however, two independent matters, according to this kind of
      theory. Other philosophers claim that the concept of health, together with the
      other medical concepts, is essentially value-laden. To establish that a person is
      healthy does not just entail some objective inspection and measurement. It
      presupposes also an evaluation of the general state of the person. A statement
      that he or she is healthy does not merely imply certain scientific facts
      regarding the person's body or mind but implies also a (positive) evaluation of
      the person's bodily and mental state. My task in this paper will be, first, to
      present the two principal rival types of theories and present what I take to be
      the main kind of reasoning by which we could assess these theories, and second,
      to present a deeper characterization of the principal rival theories of health
      and illness.

PMID- 16955346
TI  - Metal accumulation in A. baccifera growing naturally on abandoned copper tailings
      pond.
AB  - Mining activities in Rakha copper mine (Jharkhand, India) were ceased in the year
      2001, leaving a huge amount of untreated tailings in the nearby tailings pond.
      The copper tailings contained high concentrations of heavy metals (total Cu, Ni
      concentrations 1779, 564 mgkg(-1), respectively), and low contents of major
      nutrient elements and organic matter. Tailings are often very unstable, and a
      potential vegetation cover may reduce the erosion or immobilize the toxicants to
      surrounding environment by phytostabilization. However, high shoot concentrations
      of elements might disperse them and could be harmful to grazing animals. The
      objective of this study was to find out which of the three properties; low
      accumulation, root accumulation or shoot accumulation of elements (Cu, Ni, Mn,
      Zn, Pb, Cd and Co), occur in the semi aquatic species Ammania baccifera growing
      on copper tailings. Roots of this species accumulated high levels of Cu, even
      more than 1000 mg kg(-1), DW. Metals accumulated by A. baccifera were mostly
      distributed in root tissues, suggesting that an exclusion strategy for metal
      tolerance widely exists in them. Thus, establishment of such plant on copper
      tailings can be a safe method to stabilize the metals.

PMID- 16955345
TI  - Using empirical research to formulate normative ethical principles in
      biomedicine.
AB  - Bioethical research has tended to focus on theoretical discussion of the
      principles on which the analysis of ethical issues in biomedicine should be
      based. But this discussion often seems remote from biomedical practice where
      researchers and physicians confront ethical problems. On the other hand,
      published empirical research on the ethical reasoning of health care
      professionals offer only descriptions of how physicians and nurses actually
      reason ethically. The question remains whether these descriptions have any
      normative implications for nurses and physicians? In this article, we illustrate
      an approach that integrates empirical research into the formulation of normative
      ethical principles using the moral-philosophical method of Wide Reflective
      Equilibrium (WRE). The research method discussed in this article was developed in
      connection with the project 'Bioethics in Theory and Practice'. The purpose of
      this project is to investigate ethical reasoning in biomedical practice in
      Denmark empirically. In this article, we take the research method as our point of
      departure, but we exclusively discuss the theoretical framework of the method,
      not its empirical results. We argue that the descriptive phenomenological
      hermeneutical method developed by Lindseth and Norberg (2004) and Pedersen (1999)
      can be combined with the theory of WRE to arrive at a decision procedure and thus
      a foundation for the formulation of normative ethical principles. This could
      provide health care professionals and biomedical researchers with normative
      principles about how to analyse, reason and act in ethically difficult situations
      in their practice. We also show how to use existing bioethical principles as
      inspiration for interpreting the empirical findings of qualitative studies. This
      may help researchers design their own empirical studies in the field of ethics.

PMID- 16955347
TI  - Measurement of nutrients in green house soil with laser induced breakdown
      spectroscopy.
AB  - Laser-induced breakdown spectroscopy (LIBS) has been applied for the
      determination of nutrients in the green house soil samples. We determined
      appropriate spectral signatures of vital nutrients and calibrated the method to
      measure the nutrients in a naturally fertilized plot, cultivated with tomato and
      cucumber plants. From the calibration curves we predicted the concentrations of
      important nutrients such as Ca, K, P, Mg, Fe, S, Ni and Ba in the soil. Our
      measurements proved that the LIBS method rapidly and efficiently measures soil
      nutrients with excellent detection limits of 12, 9, 7, 9, 7, 10, 8 and 12 mg/kg
      for Ca, K, P, Mg, Fe, S, Ni and Ba respectively with a precision of approximately
      2%, The unique features of LIBS for rapid sample analysis demonstrated by this
      study suggests that this method offers promise for precision measurements of soil
      nutrients as compared to conventional methods in short span of time.

PMID- 16955348
TI  - Induction of apoptosis and inhibition of cell adhesive and invasive effects by
      tanshinone IIA in acute promyelocytic leukemia cells in vitro.
AB  - Tanshinone IIA, a diterpene quinone extracted from the traditional herbal
      medicine, Salvia miltiorrhiza Bunge, is used widely and successfully in clinics
      in China for treating inflammatory diseases. Recently tanshinone IIA has been
      reported to have apoptosis inducing effects on a large variety of cancer cells.
      In this study, the anti-proliferation and apoptosis inducing effects of
      tanshinone IIA as well as its influence on cell adhesion to and invasion through
      the extracellular matrix (ECM) on acute promyelocytic leukemia (APL) NB4 cells in
      vitro were studied. Cell proliferation was assessed by MTT assay, cell apoptosis
      was observed by Hoechst 33258 staining and flow cytometry (FCM); The variation of
      caspase-3 and apoptotic related genes were assayed by Western blotting, cell
      mitochondrial membrane potential as well as cell adhesive and invasive effects
      were also investigated by using standard methods. The results showed that
      tanshinone IIA exhibited induction of apoptosis by activation of caspase-3,
      downregulation of anti-apoptotic protein bcl-2 and bcl-xl and upregulation of pro
      apoptotic protein bax, as well as disruption of the mitochondrial membrane
      potential. Furthermore, treatment by tanshinone IIA could reduce cell adhesion to
      and invasion through ECM in leukemia NB4 cells. These data provide a potential
      mechanism for tanshinone IIA-induced apoptosis and cell growth inhibition in
      leukemia NB4 cells, suggesting that tanshinone IIA may serve as an effective
      adjunctive reagent for the treatment of APL.

PMID- 16955349
TI  - Fractionation and identification of 9c, 11t, 13t-conjugated linolenic acid as an
      activator of PPARalpha in bitter gourd (Momordica charantia L.).
AB  - Bitter gourd (Momordica charantia L.) is a common vegetable in Asia that has been
      used in traditional medicine for the treatment of Diabetes. PPARs are ligand
      dependent transcription factors that belong to the steroid hormone nuclear
      receptor family and control lipid and glucose homeostasis in the body. We
      previously reported that the ethyl acetate (EA) extract of bitter gourd activated
      peroxisome proliferator receptors (PPARs) alpha and gamma. To identify the active
      compound that activated PPARalpha, wild bitter gourd EA extract was partitioned
      between n-hexane and 90% methanol/10% H(2)O, and the n-hexane soluble fraction
      was further separated by silica gel column chromatography and finally by
      preparative HPLC. A transactivation assay employing a clone of CHOK1 cells stably
      transfected with a (UAS)(4)-tk-alkaline phosphatase reporter and a chimeric
      receptor of GAL4-rPPARalpha LBD was used to track the active component. Based on
      Mass, NMR, and IR spectroscopy, 9cis, 11trans, 13trans-conjugated linolenic acid
      (9c, 11t, 13t-CLN) was identified as a PPARalpha activator in wild bitter gourd.
      The isolated 9c, 11t, 13t-CLN rich fraction also significantly induced acyl CoA
      oxidase (ACO) activity in a peroxisome proliferator-responsive murine hepatoma
      cell line, H4IIEC3, implying that 9c, 11t, 13t-CLN was able to act on a natural
      PPARalpha signaling pathway as well. The content of 9c, 11t, 13t-CLN was
      estimated to be about 7.1 g/kg of our dried wild bitter gourd sample. The
      concentration of 9c, 11t, 13t-CLN and activation activity in the hydrolyzed EA
      extract of the seeds was higher than that of the flesh. The potential health
      benefits of 9c, 11t, 13t-CLN through the PPARalpha regulated mechanism are worthy
      to be further characterized in in vivo studies.

PMID- 16955350
TI  - Bioreactors for tissue engineering.
AB  - Bioreactors are essential in tissue engineering, not only because they provide an
      in vitro environment mimicking in vivo conditions for the growth of tissue
      substitutes, but also because they enable systematic studies of the responses of
      living tissues to various mechanical and biochemical cues. The basic principles
      of bioreactor design are reviewed, the bioreactors commonly used for the tissue
      engineering of cartilage, bone and cardiovascular systems are assessed in terms
      of their performance and usefulness. Several novel bioreactor types are also
      reviewed.

PMID- 16955351
TI  - Enhancement of gamma-aminobutyric acid production in Chungkukjang by applying a
      Bacillus subtilis strain expressing glutamate decarboxylase from Lactobacillus
      brevis.
AB  - For a foreign glutamate decarboxylase (GAD) to be expressed in Bacillus host
      system, a recombinant DNA (pLip/LbGAD) was constructed by ligating an LbGAD gene
      from Lactobacillus brevis OPK-3 into Escherichia coli-Bacillus shuttle vector,
      pLip. The pLip/LbGAD construct was then transformed into Bacillus subtilis. The
      culture of the transformed Bacillus strain with the pLip/LbGAD construct had
      higher GAD activity and gamma-aminobutyric acid (GABA) concentration than those
      of untransformed Bacillus counterpart. In addition, Chungkukjang, a traditional
      Korean fermented soybean product prepared by the transformed Bacillus subtilis,
      contained a significantly higher level of GABA than conventional ones. Thus, by
      introducing a foreign GAD gene, Bacillus strains have been genetically engineered
      to produce high levels of GAD and GABA.

PMID- 16955352
TI  - Improved pharmacological properties for superoxide dismutase modified with beta
      cyclodextrin-carboxymethylcellulose polymer.
AB  - Superoxide dismutase was glycosidated with cyclodextrin-branched
      carboxymethylcellulose. The modified enzyme contained 1.4 mol polymer per mol
      protein and retained 87% of the initial activity. The anti-inflammatory activity
      of superoxide dismutase was 2.2-times increased after conjugation and its plasma
      half-life time was prolonged from 4.8 min to 7.2 h.

PMID- 16955353
TI  - Continuous synthesis of alkyl ferulate by immobilized Candida antarctica lipase
      at high temperature.
AB  - 1-Pentyl, 1-hexyl and 1-heptyl ferulates were continuously synthesized at 60-90
      degrees C using a reactor system in which a column packed with ferulic acid
      powders and another column packed with immobilized Candida antarctica lipase
      particles were connected in series. Conversions greater than 0.9 were achieved
      for the synthesis of the 1-hexyl and 1-heptyl ferulates at 90 degrees C. The
      system could be stably operated for the 1-heptyl ferulate synthesis at 90 degrees
      C for at least two weeks.

PMID- 16955354
TI  - Supersaturation of dissolved H(2) and CO (2) during fermentative hydrogen
      production with N(2) sparging.
AB  - Dissolved H(2) and CO(2) were measured by an improved manual headspace-gas
      chromatographic method during fermentative H(2) production with N(2) sparging.
      Sparging increased the yield from 1.3 to 1.8 mol H(2)/mol glucose converted,
      although H(2) and CO(2) were still supersaturated regardless of sparging. The
      common assumption that sparging increases the H(2) yield because of lower
      dissolved H(2) concentrations may be incorrect, because H(2) was not lowered into
      the range necessary to affect the relevant enzymes. More likely, N(2) sparging
      decreased the rate of H(2) consumption via lower substrate concentrations.

PMID- 16955355
TI  - Wound and insect herbivory responsive genes in poplar.
AB  - Insect herbivory leads to induced resistance to subsequent infestations in
      plants. This is due in part to feeding-induced expression of genes that can lead
      to reduced palatability and/or digestibility of the plant material. We identified
      57 distinct differentially expressed genes from poplars that were either infested
      by gypsy moth (Lymantria dispar) or mechanically wounded. Eleven highly insect
      inducible genes were also found to be wound-inducible. Time course analysis
      revealed diverse timing of peak transcript accumulation. Sequence analysis of
      promoters suggested that the wound responsive elements, W and DRE, and the
      jasmonic acid responsive H motif, are over-represented in wound-induced poplar
      promoters and should be investigated further.

PMID- 16955356
TI  - Michael addition of pyrimidine with disaccharide acrylates catalyzed in organic
      medium with lipase M from Mucor javanicus.
AB  - The Michael addition of fluorouracil (0.01 mol), uracil (0.01 mol), thymine (0.01
      mol) to disaccharide acrylates (0.03 mol) was carried out in pyridine (20 ml) at
      50 degrees C for 72 h with lipase M from Mucor javanicus (200 mg). Six new
      pyrimidine derivatives containing a branched sugar were obtained in yields from
      56 to 75%.

PMID- 16955357
TI  - Increasing the catalytic performance of a whole cell biocatalyst harboring a
      cytochrome p450cam system by stabilization of an electron transfer component.
AB  - Catalytic activity of a recombinant Escherichia coli whole cell biocatalyst
      harboring a cytochrome P450cam monooxygenase system from Pseudomonas putida
      coupled with enzymatic co-factor regeneration was investigated. About 0.7
      micromol camphor was hydroxylated per mg dry cells at 4 degrees C in 50 mM
      Tris/HCl buffer (pH 7.4) when utilizing a stable putidaredoxin (Pdx) mutant,
      C73S/C85S-Pdx (Cys73Ser, Cys85Ser double mutant), instead of wild-type Pdx, which
      was about two-fold improvement in the substrate conversion. Ten-micromole camphor
      was completely hydroxylated at 20 degrees C in 6 h by 15 mg dry cell weight of
      whole cell biocatalyst including C73S/C85S-Pdx. Thus, modulation of protein
      protein interaction in multicomponent enzymatic catalysis in whole cells is
      important.

PMID- 16955358
TI  - Production kinetics and tensioactive characteristics of biosurfactant from a
      Pseudomonas aeruginosa mutant grown on waste frying oils.
AB  - Various waste frying oils (WFOs) were evaluated as substrates for rhamnolipid
      production by Pseudomonas aeruginosa mutant EBN-8 in the presence or absence of
      rhamnolipid precursor, under single-/batch-fed conditions. Soybean WFO was the
      best substrate, producing 9.3 g rhamnolipid l(-1) with the specific product yield
      of 2.7 g g(-1) h, under batch-fed cultivation with the addition of rhamnolipid
      precursor. The surface tension of the cell-free culture broth (CFCB) was 29.1 mN
      m(-1 )and the interfacial tension against n-hexadecane was <1 mN m(-1). The
      hydrocarbon/ CFCB systems showed the relative emulsion stability to be in the
      range of 89.7-92.3.

PMID- 16955359
TI  - Epicatechin and catechin may prevent coffee berry disease by inhibition of
      appressorial melanization of Colletotrichum kahawae.
AB  - Colletotrichum kahawae is the causal agent of coffee berry disease. Appressorial
      melanization is essential for the fungal penetration of plant cuticle.
      Epicatechin is abundant in green coffee berry pericarp. Inoculation of C. kahawae
      conidial suspension containing 1.2 mg epicatechin or catechin/ml did not affect
      conidial germination or appressorial formation but appressorial melanization was
      completely inhibited and infection by the treated conidia was less than 30% of
      the untreated control. Epicatechin and catechin may, therefore, prevent coffee
      berry disease by inhibition of the appressorial melanization of C. kahawae.

PMID- 16955360
TI  - Development of a quantitative method for determination of the optimal conditions
      for protoplast isolation from cultured plant cells.
AB  - An index [kv: average isolation rate of viable protoplast (number/ml min)] was
      established to evaluate the optimal conditions for protoplast isolation from
      cultured plant cells. The optimal conditions for protoplasts isolation from
      Nicotiana tabacum BY2 cultured cells could be determined on the basis of the kv
      [31.7 x 10(3) (number/ml min)]. The colony-forming efficiency of the protoplasts
      was about 46%. The optimal conditions for protoplasts isolation from Catharanthus
      roseus [kv = 38.1 x 10(3) (number/ml min)] and Wasabia japonica [kv = 14.2 x
      10(3) (number/ml min)] cultured cells could also be determined. Furthermore, a
      method for rapid regenerating cell wall of protoplast in liquid culture using
      alginate gel containing locust bean gum was developed.

PMID- 16955361
TI  - Radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia
      in a patient with orthotopic heart transplantation by bicaval anastomosis.
AB  - Patients with orthotopic heart transplantation may have a variety of arrhythmias.
      There are reports of successful radiofrequency catheter ablation of some of them.
      Two months after orthotopic cardiac transplantation by bicaval anastomosis, a 49
      year-old man developed episodes of tachycardia. The patient developed with
      dyspnoea and hypotension during typical atrioventricular nodal reentrant
      tachycardia (AVNRT) revealed by electrocardiogram. During programmed atrial
      stimulation with progressively increasing prematurity, dual auriculoventricular
      nodal physiology was observed and AVNRT was induced. This tachycardia was
      successfully eliminated without complications by radiofrequency catheter ablation
      of the slow pathway. The patient remained asymptomatic at 4-month follow-up.

PMID- 16955362
TI  - Predictors of early recurrence and delayed cure after segmental pulmonary vein
      isolation for paroxysmal atrial fibrillation without structural heart disease.
AB  - BACKGROUND: Early recurrence of atrial fibrillation (ERAF) and delayed cure are
      commonly observed after atrial fibrillation (AF) ablation. The purpose of this
      study was to determine the predictors of ERAF and delayed cure after a single
      pulmonary vein isolation (PVI) performed in paroxysmal AF patients without
      structural heart disease. METHODS AND RESULTS: In 108 consecutive patients (93
      men, 15 women; mean age 51 +/- 8 years) with paroxysmal AF and no structural
      heart disease, segmental PVI guided by a Lasso catheter was performed. Forty-one
      percent (44/108) AF patients had ERAF after a single PVI. Univariate analysis
      revealed that left atrial diameter (p = 0.004), age (p = 0.024) and P-wave
      dispersion (p = 0.045) were significantly related to ERAF. Logistic regression
      analysis revealed that left atrial enlargement was the only independent predictor
      of ERAF (odds ratio [OR] 1.17; 95% confidence interval [CI] 1.04-1.30, p =
      0.006). Delayed cure occurred in 32% (14/44) patients with ERAF. P-wave
      dispersion (p = 0.001), left atrial diameter (p = 0.008) were significantly
      related to delayed cure. P-wave dispersion was the only independent predictive
      factor of delayed cure (OR 0.91; 95% CI 0.85-0.97, p = 0.004). CONCLUSIONS:
      Elderly patients with left atrial enlargement and a high dispersion of P wave are
      susceptible to ERAF after a single PVI. Left atrial enlargement is the only
      independent predictor of ERAF. Among patients with ERAF, those with less P-wave
      dispersion and less left atrial diameter have a higher probability of delayed
      cure. P-wave dispersion can independently predict delayed cure.

PMID- 16955363
TI  - Degradability of dimethyl terephthalate by Variovorax paradoxus T4 and
      Sphingomonas yanoikuyae DOS01 isolated from deep-ocean sediments.
AB  - Two strains of bacteria were isolated from deep-ocean sediments of the South
      China Sea using enrichment culturing technique and they were identified as
      Sphingomonas yanoikuyae DOS01 (AY878409) and Variovorax paradoxus T4 (AY878410)
      based on 16S rRNA gene sequences. S. yanoikuyae DOS01 was only capable of
      transforming dimethyl terephthalate (DMTP) to monomethyl terephthalate (MMTP)
      without further degradation while V. paradoxus T4 exhibited ability in
      mineralizing DMTP as the sole source of carbon and energy. The biochemical
      pathway of DMTP degradation was through MMTP and terephthalic acid (TA) as major
      detectable degradation intermediates in the culture media by both microorganisms.
      V. paradoxus T4 utilized DMTP and MMTP via hydrolysis of diester and monoester in
      the initial steps in degradation as confirmed by total organic carbon analysis of
      the culture medium and esterase activity assay of the lysed cells and fraction.
      The specific hydrolysis activity of esterase induced by DMTP or MMTP showed that
      greater hydrolysis of p-nitrophenyl acetate by esterase induced by DMTP-grown
      cells than that induced by MMTP. Results of this research suggest that the
      cleavage of the two identical carboxylic ester groups of phthalate diester are
      carried out by highly specific esterases of the same bacteria in the environment.

PMID- 16955364
TI  - Conformational flexibility of cytokine-like C-module of tyrosyl-tRNA synthetase
      monitored by Trp144 intrinsic fluorescence.
AB  - The non-catalytic COOH-terminal module formed after proteolytic cleavage of full
      length mammalian tyrosyl-tRNA synthetase displays dual function: tRNA binding
      ability and cytokine activity. With the aim to explore the intramolecular
      dynamics of C-module in solution we used fluorescence spectroscopy to study
      conformational changes of isolated protein. We used information from fluorescence
      spectra and computational model for characterization of a microenvironment of a
      single tryptophan residue (Trp144). Its fluorescence parameters and protection
      from quenching by Cs+ ions indicate the internal localization--buried into
      protein globule. The fluorescence quenching of Trp144 by acrylamide suggests
      rapid conformation dynamics of the C-module in nanosecond time scale. The
      temperature-induced conformational changes in the C-module were monitored by the
      fluorescence measurements of Trp144 emission and by red-edge excitation shift. An
      emission maximum shift up to approximately 349 nm and significant decrease of the
      red-edge shift effect at 37-52 degrees C indicated a major conformational
      transition of Trp144 from buried native state into highly relaxing polar solvent
      environment.

PMID- 16955365
TI  - A method to calculate tissue impedance through a standard bipolar pacing lead.
AB  - The transthoracic impedance (T) and its variations may be estimated through the
      measurement of the electrical impedance between the can and the right ventricular
      coil of a defibrillation lead. This method may allow the monitoring of fluid
      overload before a heart failure attack. Aim of this study was to validate in
      vitro a method to calculate T in case of a standard bipolar pacing lead, by
      performing 3 measurements: standard unipolar impedance from the tip (Zuni-tip);
      unipolar impedance from the ring (Zuni-ring); standard bipolar impedance (Zbip).
      The formula we used is derived from the standard equivalent circuit of a pacing
      system: [Formula: see text] T represents the tissue impedance between the can and
      the electrodes of the lead. To validate the method we used a saline solution and
      3 different pacing leads manufactured by Vitatron (Vitatron BV, Arnhem, The
      Netherlands): Impulse II (high impedance lead), Crystalline ActFix (screw-in
      lead), Brilliant S+ (VDD single-lead). The measured values of the saline solution
      impedance were compared to the values calculated through the formula. RESULTS:
      The calculated impedance of the solution, evaluated through the proposed formula,
      is reliable independently of the electrode used and highly correlated to the
      corresponding measured values (R>0.9). CONCLUSION: Tissue impedance may be
      calculated from standard unipolar and bipolar impedance measurements with a
      standard bipolar pacing lead.

PMID- 16955366
TI  - Homocysteine thiolactone and human cholinesterases.
AB  - 1. The cholinergic system is important in cognition and behavior as well as in
      the function of the cerebral vasculature. 2. Hyperhomocysteinemia is a risk
      factor for development of both dementia and cerebrovascular disease. 3.
      Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) are serine
      hydrolase enzymes that catalyze the hydrolysis of the neurotransmitter
      acetylcholine, a key process in the regulation of the cholinergic system. 4. It
      has been hypothesized that the deleterious effects of elevated homocysteine may,
      in part, be due to its actions on cholinesterases. 5. To further test this
      hypothesis, homocysteine and a number of its metabolites and analogues were
      examined for effects on the activity of human cholinesterases. 6. Homocysteine
      itself did not have any measurable effect on the activity of these enzymes. 7.
      Homocysteine thiolactone, the cyclic metabolite of homocysteine, slowly and
      irreversibly inhibited the activity of human AChE. 8. Conversely, this metabolite
      and some of its analogues significantly enhanced the activity of human BuChE. 9.
      Structure-activity studies indicated that the unprotonated amino group of
      homocysteine thiolactone and related compounds represents the essential feature
      for activation of BuChE, whereas the thioester linkage appears to be responsible
      for the slow AChE inactivation. 10. It is concluded that hyperhomocysteinemia may
      exert its adverse effects, in part, through the metabolite of homocysteine,
      homocysteine thiolactone, which is capable of altering the activity of human
      cholinesterases, the most pronounced effect being BuChE activation.

PMID- 16955367
TI  - Population research of genetic polymorphism at amino acid position 631 in chicken
      Mx protein with differential antiviral activity.
AB  - A single amino acid substitution between Asn and Ser at position 631 in the
      chicken Mx protein has been reported to determine resistant and sensitive
      antiviral activity. In this study, we investigate whether various kinds of
      chicken breeds and jungle fowls carry the resistant or sensitive Mx allelic gene
      by using the mismatched PCR-restriction fragment length polymorphism (RFLP)
      technique. In total, 271 samples from 36 strains of 17 chicken breeds and from 3
      kinds of jungle fowls were examined. The rates of the resistant Mx gene and
      sensitive gene were 59.2% and 40.8%, respectively. Only a Red jungle fowl
      captured in Laos carried the resistant Mx gene, and the other three Red jungle
      fowls from Indonesia and Gray and Green jungle fowls all had the sensitive Mx
      gene. These results were confirmed by the determination of amino acid sequences
      in the GTPase effector domain of jungle fowls.

PMID- 16955368
TI  - NYD-SP15: a novel gene potentially involved in regulating testicular development
      and spermatogenesis.
AB  - By hybridizing human adult testis cDNA microarrays with human adult and embryo
      testis cDNA probes, we identified a novel human testis gene, NYD-SP15. NYD-SP15
      expression was 3.26-fold higher in adult than in fetal testis; however, there was
      almost no NYD-SP15 expression in the sperm. NYD-SP15 comprises 3364 base pairs,
      including a 1545 bp open reading frame encoding a 514 amino acid protein
      possessing 89% sequence identity with the mouse testis homologous protein. NYD
      SP15 is located on human chromosome 13q14.2. The deduced structure of the protein
      contains two dCMP_cyt_deam domains, indicating a potential functional role for
      zinc ion binding. The gene is expressed variably in a wide range of tissues, with
      high expression levels in the testis. Sequence analysis revealed that NYD-SP15 is
      not a highly conserved protein, with its distribution in high-level species such
      as vertebrates including Homo, Mus, Rattus, and Canis. The results of
      semiquantitative polymerase chain reaction in mouse testis representing different
      developmental stages indicate that NYD-SP15 expression was developmentally
      regulated. These results suggest the putative NYD-SP15 protein may play an
      important role in testicular development and spermatogenesis and may be an
      important factor governing male infertility.

PMID- 16955369
TI  - Effects of medical crisis intervention on anxiety, depression, and posttraumatic
      stress symptoms: a meta-analysis.
AB  - A meta-analysis of 11 studies (N=2124) investigating the impact of individual
      crisis intervention with medical patients yielded a significant, overall moderate
      effect size, d=0.44. The strongest effect of individual crisis intervention was
      on posttraumatic stress symptoms (d=0.57) and anxiety symptoms (d=0.52). Specific
      moderating factors, such as single versus multiple sessions, single versus
      multiple components of intervention, and level of interventionists' training,
      were also analyzed. In sum, the results support highly trained interventionists
      continuing to provide multi-session interventions in order to mitigate
      posttraumatic symptomatology following traumatic events.

PMID- 16955371
TI  - Rapid assessment of the structural relaxation behavior of amorphous
      pharmaceutical solids: effect of residual water on molecular mobility.
AB  - PURPOSE: Use RH-perfusion microcalorimetry and other analytical techniques to
      measure the interactions between water vapor and amorphous pharmaceutical solids;
      use these measurements and a mathematical model to provide a mechanistic
      understanding of observed calorimetric events. MATERIALS: Isothermal
      microcalorimetry was used to characterize interactions of water vapor with a
      model amorphous system, spray-dried raffinose. Differential scanning calorimetry
      was used to measure glass transition temperature, T (g). High-sensitivity
      differential scanning calorimetry was used to measure enthalpy relaxation. X-ray
      powder diffraction (XRPD) was used to confirm that the spray-dried samples were
      amorphous. Scanning electron microscopy (SEM) was used to examine particle
      morphology. Gravimetric vapor sorption was used to measure moisture sorption
      isotherms. Thermogravimetric analysis (TGA) was used to measure loss on drying.
      RESULTS: A moisture-induced thermal activity trace (MITAT) provides a rapid
      measure of the dependence of molecular mobility on moisture content at a given
      storage temperature. At some relative humidity threshold, RH(m), the MITAT
      exhibits a dramatic increase in the calorimetric rate of heat flux. Simulations
      using calorimetric data indicate that this thermal event is a consequence of
      enthalpy relaxation. CONCLUSIONS: RH-perfusion microcalorimetry is a useful tool
      to determine the onset of moisture-induced physical instability of glassy
      pharmaceuticals and could find a broad application to determine appropriate
      storage conditions to ensure long-term physical stability. Remarkably, thermal
      events measured on practical laboratory timescales (hours to days) are relevant
      to the stability of amorphous materials on much longer, pharmaceutically relevant
      timescales (years). The mechanistic understanding of these observations in terms
      of enthalpy relaxation has added further value to the use of RH-perfusion
      calorimetry as a rapid means to characterize the molecular mobility of amorphous
      solids.

PMID- 16955372
TI  - A boolean network modelling of receptor mosaics relevance of topology and
      cooperativity.
AB  - In the last five years data have been obtained showing that a functional cross
      talk among G Protein Coupled receptors (GPCR) exists at the plasma membrane level
      where they can dimerise and are able to generate high order oligomers. These
      findings are in agreement with the receptor mosaic (RM) hypothesis that claims
      the existence of clusters of receptor proteins at the plasma membrane level,
      where they establish mutual interactions and work as 'intelligent interfaces'
      between the extra-cellular and the intra-cellular environments. Individual
      receptor dimers can be considered to have two stable conformational states with
      respect to the macromolecular effectors: one active, one inactive. Owing to
      receptor-receptor interactions, however, a state change of a given receptor will
      change the probability of changing the state for the adjacent receptors in the RM
      and the effect will propagate throughout the cluster, leading to a complex
      cooperative behaviour. In this study we explore the properties of a RM on the
      basis of an equivalence with a Boolean network, a mathematical framework able to
      describe how complex properties may emerge from systems characterized by
      deterministic local interactions of many simple components acting in parallel.
      Computer simulations of receptor clusters arranged according to topologies
      consistent with available experimental ultrastructural data were performed. They
      indicated that RMs after a stimulation can achieve a limited number of specific
      temporary equilibrium configurations (attractors), characterized by the presence
      of receptor units frozen in the active state. They could be interpreted as a form
      of information storage and a role of RM in learning and memory could be
      hypothesized. Moreover, they seem to be at the basis of very common
      'macroscopical' properties of a receptor system, such as a sigmoidal response
      curve to an extracellular ligand, the sensitivity of the mosaic being modulated
      by changes in the topology and/or in the level of cooperativity among receptors.

PMID- 16955374
TI  - Independent origins of tetraploid cryptic species in the fern Ceratopteris
      thalictroides.
AB  - Ceratopteris thalictroides (L.) Brongn is a tetraploid fern species that contains
      at least three cryptic species, the south, the north and the third type. In this
      study we combined data from both chloroplast DNA (cpDNA) and nuclear DNA
      sequences of three diploid species and three cryptic species of C. thalictroides
      to unravel the origin of the cryptic species, particularly of the reticulate
      relationships among the diploid and tetraploid taxa in the genus Ceratopteris. Of
      the three diploid species examined, C. cornuta had cpDNA identical to that of the
      tetraploid third type plants, and this diploid species is a possible maternal
      ancestor of the tetraploid third type. Analysis of the homologue of the
      Arabidopsis thaliana LEAFY gene (CLFY1) identified ten alleles in the genus
      Ceratopteris, with six alleles found in C. thalictroides. The unrooted tree of
      the CLFY1 gene revealed four clusters. Each cryptic species showed fixed
      heterozygosity at the CLFY1 locus and had two alleles from different clusters of
      the CLFY1 tree. Consideration of the cpDNA sequences, CLFY1 genotypes of the
      cryptic species and CLFY1 gene tree in concert suggested that the cryptic species
      of C. thalictroides had originated through independent allopolyploidization
      events involving C. cornuta and two unknown hypothetical diploid species.

PMID- 16955373
TI  - Environmental enrichment reduces the function of D1 dopamine receptors in the
      prefrontal cortex of the rat.
AB  - Environmental enrichment produces changes in spontaneous and psychostimulant
      induced motor activity. Dopamine in the prefrontal cortex (PFC), through the
      activation of D1 receptors, has been suggested to play a role in modulating motor
      activity. The present study investigated the effects of environmental enrichment
      on spontaneous motor activity, prefrontal acetylcholine release following local
      D1 receptor stimulation and D1 receptor expression in the PFC. Male wistar rats
      (3 months of age) were housed in enriched or isolated conditions during 90 days.
      Animals were then implanted with guide cannulae to perform microdialysis
      experiments in the PFC. Spontaneous motor activity and acetylcholine
      extracellular concentrations were monitored simultaneously. Also spontaneous
      motor activity was measured in an open field. On completion of the experiments,
      the density of D1 receptors in the PFC was studied by immunocytochemistry. Rats
      housed in an enriched environment showed significantly lower spontaneous motor
      activity in the open field compared to isolated animals. Perfusion of the D1
      agonist SKF38393 (50 microM; 40 min) in the PFC produced long lasting increases
      of spontaneous motor activity and of local dialysate concentrations of
      acetylcholine in both groups of rats. However, increases of both motor activity
      and acetylcholine concentrations were significantly lower in enriched compared to
      isolated animals. Moreover, the density of D1 receptors in the PFC was
      significantly reduced in animals housed in an enriched environment. These results
      are the first evidence suggesting that environmental enrichment during adult life
      changes the function of D1 dopamine receptors in the PFC.

PMID- 16955375
TI  - Post-pollination reproductive isolation between diurnally and nocturnally
      flowering daylilies, Hemerocallis fulva and Hemerocallis citrina.
AB  - To examine whether floral and post-pollination isolation develops independently
      or not, we conducted a crossing experiment between Hemerocallis fulva and
      Hemerocallis citrina that shows large floral divergence adapted for diurnal and
      nocturnal pollinators that have been believed to be fully cross-fertile. Flowers
      of the two species from sympatric populations were hand-pollinated with
      conspecific pollen from the same population (control), interspecific pollen from
      the same area (sympatric cross), and interspecific pollen from the different area
      (allopatric cross). After capsule dehiscence, the fruit set, seed set per fruit
      and seed set per flower were determined among three cross categories. The seed
      sets per flower were 32 and 77% lower in sympatric and allopatric crosses than in
      the control when H. fulva was the pollen recipient. There was no difference in
      three reproductive measures among the cross categories when H. citrina was the
      pollen recipient. This finding indicates that post-pollination isolation does
      exist between H. fulva and H. citrina, although it is partial, asymmetric, and
      weakened in sympatry. Our result suggests that floral and post-pollination
      isolation may develop independently, and reinforcement may not be a general
      phenomenon in plants.

PMID- 16955377
TI  - Chronic mesenteric ischemia: stenting of mesenteric arteries.
AB  - This article focuses on stent placement in mesenteric arteries in patients with
      the rare diagnosis of chronic mesenteric ischemia. We present a survey from the
      initial stage of recognition of this gastrointestinal disorder and its
      manifestations to treatment by stenting to avoid further ischemic episodes and
      bowel infarction and necrosis. The advantages of stent placement in splanchnic
      arteries are discussed in comparison to open surgical revascularization.

PMID- 16955376
TI  - 99mTc-Sestamibi, a sensitive probe for in vivo imaging of P-glycoprotein
      inhibition by modulators and mdr1 antisense oligodeoxynucleotides.
AB  - PURPOSE: We tested the suitability of (99m)Tc-sestamibi to image the inhibition
      of P-glycoprotein (Pgp)-mediated multidrug resistance in tumor cells and
      xenografts after antisense treatment and/or inhibition with a novel Pgp modulator
      WK-X-34. PROCEDURE: Pgp inhibition was measured by daunorubicin transport assays
      and fluorescence microscopy in resistant A2780/Adr cells treated with WK-X-34 and
      antisense. A2780/Adr xenograft mice were dosed with mdr1 antisense
      oligodeoxynucleotides intratumorally for three days; next, mice were treated with
      WK-X-34, followed by (99m)Tc-sestamibi injection. Mice were imaged, sacrificed,
      and tissues collected. Images and isolated tissues were analyzed for (99)Tc
      distribution. Pgp expression was analyzed by immunofluorescence and reverse
      transcription-polymerase chain reaction. RESULTS: Both WK-X-34 and mdr1 antisense
      treatments significantly inhibited Pgp activity in vitro and in xenografts.
      Biodistribution results correlated with results from the (99m)Tc-sestamibi
      images. Mdr1 mRNA and Pgp were significantly down-regulated by antisense
      treatments. CONCLUSIONS: (99m)Tc-sestamibi is a sensitive probe to monitor Pgp
      inhibition by different mechanisms in vivo in tumor xenografts.

PMID- 16955378
TI  - Acute pancreatitis and a long common channel.
AB  - BACKGROUND: As sphincter action does not functionally affect the union in
      pancreaticobiliary maljunction (PBM), two-way regurgitation occurs. We
      investigated the features of acute pancreatitis associated with patients
      displaying a long common channel. METHODS: We reviewed 3210 endoscopic retrograde
      cholangiopancreatograms. PBM was diagnosed in 107 patients with a long common
      channel in which communication between the pancreatic and bile duct was
      maintained even during sphincter contraction. High confluence of
      pancreaticobiliary ducts (HCPBD) was diagnosed in 60 patients with a common
      channel >or=6 mm long in which communication between the two ducts was occluded
      with sphincter contraction. RESULTS: Of patients with PBM, four had acute
      pancreatitis. Etiology of acute pancreatitis in the two patients was suspected to
      involve impaction in a long common channel. Of patients with HCPBD, 17 displayed
      acute pancreatitis. Three patients had a history of excessive alcohol intake and
      10 patients were associated with choledocholithiasis or cholecystitis. The
      remaining four patients had no history of them. CONCLUSIONS: Acute pancreatitis
      occurs in 13% of patients with a long common channel. Obstruction of a long
      common channel by stones easily induces bile flow into the pancreas. Even if no
      obstruction is present, biliopancreatic reflux induces acute pancreatitis in some
      patients.

PMID- 16955379
TI  - Prostate cancer: value of magnetic resonance spectroscopy 3D chemical shift
      imaging.
AB  - The results of recent studies of magnetic resonance imaging (MRI) combined with
      three-dimensional magnetic resonance spectroscopic imaging (3D-MRSI) demonstrate
      that the MRI/3D-MRSI exam is a unique method by which to noninvasively study the
      cellular metabolism and anatomy of the prostate. 3D-MRSI is emerging as the most
      specificity tool for non-invasive evaluation of the prostate cancer. The results
      of current MRI/3D-MRSI studies also provide evidence that the magnitude of
      metabolic changes in regions of cancer before therapy, as well as the extent of
      the time course of metabolic changes after therapy, may improve our understanding
      of cancer aggressiveness. Assessment of cancer spread outside the prostate can be
      significantly improved by combining MRI findings with estimates of metabolic
      abnormalities provided by 3D-MRSI. Clinically, combined MRI/3D-MRSI has already
      demonstrated a potential for improved diagnosis, staging, and treatment planning
      for patients with prostate cancer. This article reviewed the value of 3D-MRS
      imaging for the diagnosis, localization, staging, aggressiveness, and treatment
      planning of prostate cancer.

PMID- 16955380
TI  - Analysis of the X-ray work flow in two diagnostic imaging departments with and
      without a RIS/PACS system.
AB  - A traditional radiological workflow is compared with one based on radiology
      information system/picture archiving and communication system (RIS/PACS). X-ray
      workflow process was considered in both radiology departments. First, the study
      identified the main phases of the research work as follows: Process Analysis,
      Data Collection and Elaboration, Interpretation. Afterwards, the main steps of
      the whole image acquisition process were defined, and each step was divided into
      a number of elementary operations. Then, the time required to complete each of
      these was measured. Data collected were elaborated and synthesized to obtain time
      frequency distributions for each step and evaluation of the total time for the
      whole working flow. Statistical elaboration of the collected data shows that x
      ray working time decreases, between 35% and 57%, when RIS/PACS is used. Detailed
      analysis of the whole working process allows identification of possible critical
      points to improve the image acquisition process.

PMID- 16955381
TI  - Improving resectability of hepatic colorectal metastases: expert consensus
      statement.

PMID- 16955382
TI  - Pancreatic resections after chemoradiotherapy for locally advanced ductal
      adenocarcinoma: analysis of perioperative outcome and survival.
AB  - BACKGROUND: The most accepted treatment for locally advanced pancreatic cancer is
      chemoradiotherapy. However, indications to and results of pancreatic resections
      after chemoradiation are not yet defined. METHODS: From June 1999 to December
      2003, 28 patients with locally advanced pancreatic cancer (group 1) were enrolled
      for institutional trials of gemcitabine-based chemoradiotherapy. Tumors were
      stratified as unresectable or borderline resectable according to the pattern of
      vascular involvement at pretreatment computed tomographic scan. Patients with
      partial response or stable disease and in-range Ca19-9 were surgically explored.
      Perioperative outcome and survival of group 1 were compared with 44 patients
      primary resected for localized cancer with or without adjuvant treatment in the
      same time period (group 2). RESULTS: Only one unresectable tumor was successfully
      resected compared to 7 out of 18 (39%) that were borderline resectable.
      Operations after chemoradiation were 1 hour longer and postoperative stays 5 days
      longer, but transfusion rate, morbidity, and mortality were not significantly
      different. Median survival was 15.4 months for group 1 (>21 for resected vs. 10
      for not resected, P < 0.01) and 14 months for group 2. In both groups, a disease
      free survival beyond 24 months was recorded only among patients resected with
      negative margins. CONCLUSIONS: The conversion of an unresectable cancer to a
      resectable one is a rare event. On the contrary, the resection of a borderline
      resectable tumor was successfully accomplished in one-third of cases.
      Chemoradiotherapy did not increase the operative risk, but the interventions were
      more technically demanding and required a longer postoperative stay. Patients
      resected after chemoradiation for a locally advanced tumor had at least the same
      survival as those primary resected for a localized one. Only R0 resections in
      both groups gave the chance of disease-free survival longer than 24 months.

PMID- 16955383
TI  - Lessons learned...

PMID- 16955384
TI  - Chemotherapy and regional therapy of hepatic colorectal metastases: expert
      consensus statement.

PMID- 16955385
TI  - Extent of lymph node retrieval and pancreatic cancer survival: information from a
      large US population database.
AB  - BACKGROUND: Operative therapy of pancreatic cancer is associated with poor
      survival because of high recurrence rates after pancreatectomy. The effect of
      lymph node (LN) dissection on survival continues to be debated. METHODS: A
      pancreatic cancer data set was created through structured queries to the
      Surveillance, Epidemiology, and End Results 1973 to 2000 database. Stage
      information was created according to 6th edition American Joint Committee on
      Cancer tumor-node-metastasis criteria, and the effect of LN number on survival
      was analyzed. RESULTS: Out of a cohort of 20,631 patients with carcinomas of the
      exocrine pancreas, surgical details were available for 2,787 patients. Procedures
      included pancreatoduodenectomies (n = 1848; 66%), radical regional
      pancreatectomies (n = 516; 19%), other partial resections (n = 316; 11%), and
      total pancreatectomies (n = 107; 4%). For 1666 of these patients with complete
      clinicopathologic information, the median age was 66 years (range, 22-96 years),
      with an equal sex ratio. The median number of total LNs examined was 7 (range, 1
      52), of positive LNs was 1 (range, 0-34), and of negative LNs was 6 (range, 0
      30). Multivariate survival analysis yielded these prognostic variables: number of
      LNs examined, number of positive LNs, tumor size, extrapancreatic extension,
      radiotherapy (all P < .0001), and age (P = .0009). The greatest survival
      differences were observed for negative LN counts of 10 to 15. CONCLUSIONS: Stage
      based survival prediction of pancreatic cancer is strongly influenced by total LN
      counts and numbers of negative LNs obtained. Although the mechanism remains
      unclear and could reflect confounding factors (margin status and institutional
      volume), an attempt to resect and examine at least 15 LNs to yield preferably
      between 10 and 15 negative LNs seems sensible for curative-intent pancreatectomy.

PMID- 16955386
TI  - An endogenous inhibitor of angiogenesis derived from a transitional cell
      carcinoma: clipped beta2-glycoprotein-I.
AB  - BACKGROUND: Invasive cell carcinoma of the bladder often develops after complete
      transurethral excision of superficial transitional cell carcinoma. It has been
      postulated that primary tumors release angiogenesis-blocking proteins which
      suppress distant metastases. We have identified an endogenous protein which might
      be responsible for tumor dormancy. METHODS: A transitional cell carcinoma cell
      line was developed (UMUC-3i) which inhibits the growth of a tumor implant at a
      distant site in SCID mice. Conditioned media of UMUC-3i cultured cells was first
      pooled and then fractioned, and the capacity of individual components to block
      endothelial cell growth was tested. The protein fraction responsible for blocking
      endothelial cell growth was identified by N-terminal amino acid sequencing as
      well as by mass-spectrometry. The effects of the purified protein in preventing
      endothelial cell proliferation and tube formation in an in vitro angiogenesis
      assay was investigated. RESULTS: The plasma protein beta(2)-glycoprotein-I
      (beta(2)gpI) was isolated and identified from conditioned medium of UMUC-3i
      cultured cells. Based on the in vitro angiogenesis assay, beta(2)gpI strongly
      inhibited endothelial cell growth and tube formation, whereby the inhibitory
      activity corresponded to the clipped version of beta(2)gpI (cbeta(2)gpI).
      Clipping was induced by adding plasmin at a molar ratio 1:15 (plasmin:substrate).
      Further analysis indicated that cbeta(2)gpI effects were mediated by annexin II
      surface receptors expressed on endothelial cells. CONCLUSIONS: cbeta2gpI may be
      involved in blocking angiogenic processes and bladder cancer progression. In this
      case, cbeta2gpI may be a promising tool in bladder cancer therapy.

PMID- 16955387
TI  - Extramammary Paget's disease: isolated localization on the groin--wide local
      excision with immediate reconstruction.
AB  - BACKGROUND: Extramammary Paget's disease is a rare cutaneous malignancy, which
      occurring frequently in the elderly and affecting primarily the genital,
      perianal, and axillary regions. Unfortunately, surgical and ablative treatment
      modalities for extramammary Paget's disease have a high recurrence rate and are
      often associated with significant morbidity. METHODS: We present a case of a 51
      year-old Caucasian man with Paget's disease of the right groin. The isolated
      localization of Paget's disease in the groin is extremely rare. Wide local
      excision of the tumor is currently the standard of care treatment. All
      publications found in the literature reporting this rare entity were reviewed for
      the purpose of further delineating a treatment regimen for this rare pathology.
      RESULTS: Six years after surgery, the patient remains disease free with a very
      acceptable aesthetic result. Currently, only 11 cases of Paget's disease have
      been reported with an isolated localization to the groin. CONCLUSIONS: Paget's
      disease of the groin has an extremely low incidence. Various treatments are
      described in the literature, early wide local excision may be the treatment of
      choice.

PMID- 16955388
TI  - Carbon monoxide: the bad and the good side of the coin, from neuronal death to
      anti-inflammatory activity.
AB  - The double origin of carbon monoxide (CO) as an atmospheric pollutant or as an
      endogenous gaseous modulator of many pathophysiological processes prompted us to
      review some aspects of the bad side and of the good side of coin among the
      pleiotropic effects of CO. On the bad side of the coin, we focus on the interval
      form in acute CO poisoning, discussing experimental evidence suggesting that the
      delayed neuropathology after CO poisoning is a free radical-driven event. In this
      context, we challenge the mandatory place of hyperbaric oxygen therapy (HBO) in
      CO poisoning as a possible summation of oxy-radicals generated by HBO and the
      free radical cascade set in motion during the reoxygenation phase of acute CO
      poisoning. We also discuss an opposing view, which provides evidence suggesting
      that HBO therapy actually decreases the load of free radicals in acute CO
      poisoning and may be beneficial in preventing delayed neuropsychiatric
      sequelae.On the good side of the coin, we briefly outline the endogenous
      generation of CO and the leading role of heme-oxygenases (HO) in relation to the
      place of CO in biology and medicine. The main focus of this section is on the
      growing literature on CO and inflammation. Here we report on in-vitro and in-vivo
      studies on the modulation afforded by exogenously administered/endogenously
      produced CO in a variety of experimental and clinical settings of inflammation.
      Our recent studies on experimental models of allergic inflammation are also
      discussed, and the CO-releasing molecules envisaged as potential anti
      inflammatory drugs suitable for clinical use.

PMID- 16955389
TI  - Cloning of cyclooxygenase-1b (putative COX-3) in mouse.
AB  - OBJECTIVES: To clone and sequence cyclooxygenase-1b (COX-1b, also known as COX-3)
      mRNA and to generate an antibody against the mouse COX-1b protein and to
      demonstrate its existence in vivo in mouse tissues. ANIMALS: 10 C57BL/6 mice, 4
      COX-1 knockout mice and 4 COX-1 wild type mice were used. METHODS: COX-1b mRNA
      sequence was determined by RT-PCR amplification using specific primers followed
      by DNA sequencing. COX-1b protein expression was determined by Western blotting.
      RESULTS: The mouse COX-1b mRNA is a splice variant of the COX-1 mRNA generated by
      the retention of intron-1. COX-1b mRNA encodes a 127 amino acid protein with no
      similarity with known COX sequences. We generated an anti-mouse COX-1b antibody
      and demonstrated the existence of COX-1b protein in vivo with the highest
      expression in kidney, heart, and neuronal tissues. We also detected COX-1b mRNA
      and protein expression in COX-1 knockout mice. CONCLUSIONS: In mouse, COX-1b
      encodes a protein with a completely different amino acid sequence than COX-1 or
      COX-2; therefore it is improbable that COX-1b in this species plays a role in
      prostaglandin-mediated fever and pain. In addition, the COX-1(-/-) mouse is not a
      COX-1b(-/-) mouse, therefore it cannot be used to elucidate the function of the
      COX-1b protein.

PMID- 16955390
TI  - Toll-like receptor expression in chronic hepatitis C: correlation with pro
      inflammatory cytokine levels and liver injury.
AB  - BACKGROUND/AIMS: Toll-like receptors (TLR's) are critical receptors that promote
      innate immune responses to pathogen-associated molecular patterns. Activation of
      TLR's leads to production of pro-inflammatory cytokines such as tumour necrosis
      factor (TNF)-alpha. This study investigates whether peripheral blood monocyte
      expression of TLR's is disturbed in patients with chronic hepatitis C and whether
      levels of expression of these molecules are significantly correlated with
      hepatitis C virus (HCV) genotype, viral load, hepatic necroinflammatory activity,
      histological stage and circulating TNF-alpha concentrations. METHODS: In 18 non
      cirrhotic patients with biopsy-proven, virologically-confirmed chronic hepatitis
      C and 32 controls, we measured expression of TLR2 and TLR4 on peripheral blood
      monocytes. HCV genotype, viral load, serum alanine aminotransferase (ALT) levels,
      histological stage of disease and circulating TNF-alpha and endotoxin levels were
      also determined. RESULTS: Peripheral blood monocyte expression of TLR2 and TLR4
      were significantly increased in patients with chronic hepatitis C compared to
      controls, irrespective of HCV genotype or histological stage of disease.
      Circulating levels of TNF-alpha were also significantly increased in patients
      with chronic hepatitis C. In both the overall study cohort and patients with
      chronic hepatitis C, monocyte expression of TLR2, but not of TLR4, correlated
      significantly with serum TNF-alpha levels. In patients with chronic hepatitis C,
      monocyte expression of TLR2, but not of TLR4, also correlated significantly with
      serum ALT levels. Expression of TLR's was not significantly correlated with viral
      load. CONCLUSIONS: Up-regulation of peripheral blood monocyte expression of TLR2
      and TLR4 occurs in patients with chronic hepatitis C. Increased monocyte
      expression of TLR2, but not of TLR4, correlates significantly with both increased
      circulating TNF-alpha levels and hepatic necroinflammatory activity in this
      disorder.

PMID- 16955391
TI  - Airway hyperresponsiveness induced by repetitive intraperitoneal injection of
      lipopolysacharide and the involvement of inflammation and nitric oxide in guinea
      pigs.
AB  - OBJECTIVE: Airway hyperresponsiveness (AHR) is involved in bronchial asthma and
      chronic obstructive pulmonary disease (COPD) and produces respiratory symptoms.
      Lipopolysaccharide (LPS) has been found to be significantly related to the
      severity of asthma. However, its clinical mechanism still remains controversial.
      This study investigated the in vivo effect of repetitive intraperitoneal
      administration of lipopolysaccharide (LPS) on airway hyperresponsiveness (AHR) in
      guinea pigs and the possible involvement of inflammation, nitric oxide (NO) and
      nitric oxide synthase (NOS). METHODS: There were two exposure groups for
      intraperitoneal LPS injection: (1) LPS was given at a dose of 1 mg x kg(-1),
      followed by sterile saline (NS) 1 ml x kg(-1) 8 h later every 24 h; (2) LPS was
      given at a dose of 0.5 mg x kg(-1) two times with an interval of 8 h every 24 h.
      Each exposure regime was repeated 4 times. Control animals were given NS and 6
      naive guinea pigs were used as baseline control. Determinations were made 24 h
      after each exposure. RESULTS: Persistent AHR occurred 24 h after the third and
      fourth exposures to LPS in the first exposure group (at one dose), but occurred
      earlier after the exposures to LPS in the second exposure group (at divided
      doses). The numbers of total cells and neutrophils were elevated initially but
      subsided subsequently in LPS-treated groups. No evidence of morphological changes
      in the small airways was found 24 h after any of the exposures. The Ca(2+)
      dependent and Ca(2+)-independent NOS activities (mainly produced by iNOS) in the
      BALF, as well as the production of NO, were significantly elevated 24 h after any
      of third and fourth exposures in LPS-treated groups. CONCLUSIONS: Our results
      demonstrate that repetitive intraperitoneal LPS can induce persistent AHR which
      occurs earlier when the frequency of injection increase, and an elevation of NO
      production and iNOS activity may be involved in is systemic-LPS-induced AHR.

PMID- 16955392
TI  - Gene expression profiling of human synovial sarcoma cell line (Hs701.T) in
      response to IL-1beta stimulation.
AB  - OBJECTIVE: Synovial sarcoma (SS) is a malignant mesenchymal tumor that accounts
      for 5-10% of all soft tissue sarcoma. IL-1beta, a pleiotrophic cytokine, has been
      found in the tumor microenvironment which plays crucial roles in the pathogenesis
      of tumors. METHODS: In this study, we used Hs701.T as a cellular model to study
      the short-term (4-h) and long-term (48-h) stimulatory effect of IL-1beta on cell
      proliferation and differential gene expression. RESULTS: The results showed that
      IL-1beta can stimulate cell proliferation through activation of NF-kappaB and AP
      1 transcription factors; sequentially triggers the expression of genes related to
      tumor progression. The microarray data indicated that most of the up-regulated
      genes were related to tumor progression. Five candidate genes which are involved
      in the mediation of proliferation (IL-6), apoptosis (Hsp27 and Daxx), and
      angiogenesis (PlGF and SPARC) were further validated by RT-PCR. CONCLUSION: These
      findings may be useful for understanding the pathogenesis of synovial sarcoma.

PMID- 16955393
TI  - Reduced cholesterol accumulation by leptin deficient (ob/ob) mouse macrophages.
AB  - OBJECTIVE: Although presenting many aspects of the metabolic syndrome, leptin
      deficient (ob/ob) mice do not spontaneously develop atherosclerosis. To examine
      the role of leptin in foam cell formation we analyzed ob/ob leukocyte
      inflammation markers and macrophage cholesterol accumulation. METHODS: Resident
      and thioglycollate (TG) elicited peritoneal cells of ob/ob and wildtype mice were
      studied. Activation markers, scavenger receptors (SR) and cholesterol
      accumulation were analyzed using flow cytometry and Taqman analysis. Cytokines,
      haptoglobin, adiponectin and amyloid A levels were analyzed with ELISA. RESULTS:
      Macrophages of ob/ob mice had reduced expression of MHC class II, CD11b, CD40, SR
      A and CD36 and reduced cholesterol accumulation in vitro. Plasma haptoglobin was
      increased and T-cell IFNgamma was reduced in ob/ob mice. Peritoneal TG
      instillation induced an unexpectedly weak inflammatory response in ob/ob mice.
      CONCLUSIONS: The ob/ob mice had a reduced inflammatory response and reduced
      macrophage cholesterol accumulation in vitro. The data suggest decreased foam
      cell formation and atherosclerosis development in ob/ob mice.

PMID- 16955394
TI  - Radial scar/complex sclerosing lesion of the breast--value of ultrasound.
AB  - PURPOSE: Although benign, radial scar/complex sclerosing adenosis is a lesion
      which histopathologically resembles tubular carcinoma. On physical examination,
      it is difficult to distinguish radial scar from a malignant tumour. Mammography
      cannot differentiate radial scar from malignancy. This clinical study aims to
      delineate the role of preoperative ultrasonography with emphasis on the question
      whether ultrasonography could lower the number of false-positive readings and
      therefore the number of open biopsies required. MATERIALS AND METHODS: In this
      examination, we present the clinical, mammographic, ultrasonographic, and
      histopathological features of 6 cases of radial scars. RESULTS: Although most
      authors describe radial scars as non-palpable, 2 of 6 lesions were indeed
      palpable. On mammograms, radial scars have a spiculated appearance, a feature
      observed in all of our cases. Numerous ultrasonographic characteristics are
      listed in the literature, but ultrasonography is not reported to have clear-cut
      advantages. CONCLUSION: Although this study did not elucidate any unique
      ultrasonographic features to characterise these lesions, the analysis of all
      ultrasonographic results made us recognise a set of "nearly specific
      ultrasonographic features" of radial scars. Current B-mode imaging does not
      appear to lead to the desirable reduction of the rate of unnecessary open
      biopsies.

PMID- 16955395
TI  - Lipids and lipidomics.

PMID- 16955396
TI  - The supramolecular chemistry of organic-inorganic hybrid materials.
AB  - The combination of nanomaterials as solid supports and supramolecular concepts
      has led to the development of hybrid materials with improved functionalities.
      These "hetero-supramolecular" ideas provide a means of bridging the gap between
      molecular chemistry, materials sciences, and nanotechnology. In recent years,
      relevant examples have been reported on functional aspects, such as enhanced
      recognition and sensing by using molecules on preorganized surfaces, the
      reversible building of nanometer-sized networks and 3D architectures, as well as
      biomimetic and gated chemistry in hybrid nanomaterials for the development of
      advanced functional protocols in three-dimensional frameworks. This approach
      allows the fine-tuning of the properties of nanomaterials and offers new
      perspectives for the application of supramolecular concepts.

PMID- 16955398
TI  - Chemokine receptor expression profiles in nasopharyngeal carcinoma and their
      association with metastasis and radiotherapy.
AB  - Nasopharyngeal carcinoma (NPC) is an epithelial cancer that metastasizes
      predictably to cervical lymph nodes or distant organs. To assess whether the
      chemokine receptors of NPC cells play important roles in metastasis and are
      associated with radiotherapy history, the significance of various chemokine
      receptors (CCR1-10, CXCR1-6, XCR1, and CX3CR1) in NPC cell lines (TW01, TW04,
      HONE1, BM1, and AS1) and 52 NPC tumour biopsies from 48 patients with NPC was
      evaluated by mRNA and cytometric analyses, chemotaxis and actin polymerization
      assays, and immunohistochemical staining. Quantitative real-time reverse
      transcription-polymerase chain reaction revealed substantial expression of CCR7,
      CCR9, CXCR4, and CXCR6 mRNA in all the NPC cell lines. Of these, however, only
      CCR7, CXCR4, and CXCR6 were functional in NPC cells. Negative immunoreactivity
      for CCR7, CXCR4, and CXCR6 was demonstrated in almost all nasopharyngeal (NP)
      specimens from patients with primary NPC (n = 12) and in those with regional
      metastatic NPC (n = 15). However, expression of two or three of these chemokine
      receptors was demonstrated in NP specimens from patients with liver metastasis.
      Strong positivity was demonstrated for all three of these chemokine receptors in
      almost all of the regional and distant metastasis specimens. Significant
      differences in the expression of CCR7, CXCR4, and CXCR6 were found between
      primary tumours and metastases (p < 0.001, p < 0.001, and p < 0.002,
      respectively). This observation was further confirmed by laser capture
      microdissection of freshly frozen tumours from primary (n = 5) and metastatic (n
      = 8) NPC sites (p = 0.04, 0.03, and 0.03 for CCR7, CXCR4, and CXCR6,
      respectively). Finally, significant differences in CXCR4 expression were
      demonstrated between de novo and post-radiotherapy groups (1/22 vs. 5/8; p <
      0.003). It appears reasonable to conclude, therefore, that CCR7, CXCR4, and CXCR6
      are expressed and active in human NPC metastases, while CXCR4 expression is
      associated with radiotherapy history.

PMID- 16955399
TI  - Identification of ABR-215050 as lead second generation quinoline-3-carboxamide
      anti-angiogenic agent for the treatment of prostate cancer.
AB  - BACKGROUND: Linomide, Figure 1, produces robust and consistent in vivo growth
      inhibition of prostate cancer models via its anti-angiogenic activity and
      inhibition of autoimmune encephalomyelitis models of multiple sclerosis (MS). MS
      clinical trials were discontinued because of unacceptable toxicity, due to dose
      dependent induction of proinflammation. METHODS: Therefore, linomide analogs were
      initially screened to determine their in vivo potency to inhibit growth of the
      Dunning R-3327 AT-1 rat prostate cancer model in rats and their potency to
      inhibit angiogenesis in a Matrigel assay in mice. RESULTS: Based upon its
      superior potency (i.e., 30- to 60-fold more potent than linomide) in these assays
      and its lack of a proinflammation in the Beagle-dog, ABR-215050 (tasquinimod),
      Figure 1, was characterized for dose-response ability to inhibit the growth of a
      series of four additional human and rodent prostate cancer models in mice.
      Pharmacokinetic analysis following oral dosing documented that blood and tumor
      tissue levels of ABR-215050 as low as 0.5-1 microM are therapeutically effective.
      This efficacy is correlated with inhibition of angiogenesis in a variety of
      assays (endothelial capillary tube formation, aortic ring assay, chorioallantoic
      membrane assay, real-time tumor blood flow and PO(2) measurements, tumor blood
      vessel density, and tumor hypoxic and apoptotic fractions). CONCLUSIONS: Based
      upon its robust and consistent anti-angiogenic activity and thus tumor growth,
      ABR-215050 has entered clinical trials for the treatment of prostate cancer.

PMID- 16955401
TI  - Control of prostate cancer spheroid growth using 213Bi-labeled multiple targeted
      alpha radioimmunoconjugates.
AB  - BACKGROUND: Micrometastasis is a major problem for prostate cancer (CaP)
      patients. Our study investigated the therapeutic potential of multiple targeted
      alpha-therapy (MTAT) in the treatment of CaP micrometastases (spheroids) using
      (213)Bi-labeled multiple targeted alpha-radioimmunoconjugates. METHODS: The
      expression of multiple tumor-associated antigens (TAAs) on frozen sections of
      human fresh CaP tissues and spheroids cultured from DU 145 and LNCaP-LN3 CaP cell
      lines was detected by immunohistochemistry and flow cytometry. Targeting vectors
      were two monoclonal antibodies (MAbs), and plasminogen activator inhibitor type 2
      (PAI2) that binds to cell surface urokinase plasminogen activator (uPA). These
      vectors were labeled with (213)Bi using standard methodology. DU 145 and LNCaP
      LN3 spheroids were incubated with different activities of test and control alpha
      conjugates (ACs), and spheroid growth was measured for volume change and growth
      delay over a 50-day period using light microscopy. RESULTS: TAAs were expressed
      heterogeneously on frozen sections from human CaP tissues and CaP spheroids. MTAT
      combining three ACs (one-third dose of each) with an activity of 6.4 MBq/ml
      completely targeted small DU 145 and LNCaP-LN3 spheroids (diameter <100 microm)
      and slightly regressed the growth of medium spheroids (180-200 microm); MTAT with
      2.2 or 4.8 MBq/ml activities delayed the growth of tumor spheroids. CONCLUSIONS:
      Our results suggest that the cytotoxicity of MTAT to CaP spheroids is highly
      dependent on antigenic expression, concentration of radioactivity and spheroid
      size. MTAT may be a potent therapeutic agent for micrometastases, effectively
      targeting small CaP cell clusters, and overcoming the heterogeneous expression of
      targeted antigens.

PMID- 16955402
TI  - Identification of a heat-shock protein Hsp40, DjB1, as an acrosome- and a tail
      associated component in rodent spermatozoa.
AB  - Iba1 is a 17-kDa EF-hand protein highly expressed in the cytoplasm of elongating
      spermatids in testis. Using Iba1 as a bait, we performed yeast Two-hybrid
      screening and isolated a heat-shock protein Hsp40, DjB1, from cDNA library of
      mouse testis. To characterize DjB1 that is encoded by Dnajb1 gene, we carried out
      immunoblot analyses, in situ hybridization, and immunohistochemistry. Immunoblot
      analyses showed that DjB1was constitutively expressed in mouse testis and that
      its expression level was not changed by heat shock. Dnajb1 mRNA was exclusively
      expressed in spermatocytes and round spermatids in mouse testis, and Dnajb1
      protein DjB1 was predominantly expressed in the cytoplasm of spermatocytes, round
      spermatids, and elongating spermatids. In mature mouse spermatozoa, DjB1 was
      localized in the middle and the end pieces of flagella as well as in association
      with the head (acrosomal region). Association of DjB1 with the acrosomal region
      in sperm head was also observed in rat spermatozoa. These data suggested that
      DjB1, which was constitutively expressed in postmeiotic spermatogenic cells in
      testis, was integrated into spermatozoa as at least two components, that is,
      sperm head and tail of rodent spermatozoa.

PMID- 16955403
TI  - Cadherin in developing and maturing cysts of Torpedo Marmorata Testis.
AB  - We investigated the presence of cadherins, Ca++ dependent cell-cell adhesion
      molecules, during the development and maturation of cysts in the testis of the
      spotted ray Torpedo marmorata. Using different anti-cadherin antibodies, we
      provide evidence by means of immunohistochemistry and immunoblotting that
      cadherins are involved in the interaction between Sertoli and germ cells. During
      the development and maturation of cysts, in fact, cadherins occur between Sertoli
      and germ cells when they begin to interact to build a cyst. Later on, the
      presence of cadherins between Sertoli and germ cells persists; furthermore,
      during the formation of spermatoblast, it is also evident at the level of
      indentations, arising from Sertoli cells and encompassing germ cells. Finally,
      the present findings strongly suggest that cadherins are also involved in the
      spermiogenesis as germ cells, when male gamete differentiation starts, are
      intensively stained, while, when spermiation is completed, the spermatozoa appear
      unlabeled.

PMID- 16955404
TI  - Insulin-like growth factor-I promotes resistance of bovine preimplantation
      embryos to heat shock through actions independent of its anti-apoptotic actions
      requiring PI3K signaling.
AB  - For the bovine preimplantation embryo, insulin-like growth factor-I (IGF-I) is a
      survival factor that blocks the induction of apoptosis and reduces the decrease
      in development caused by heat shock. The first objective was to determine the
      signaling pathways whereby IGF-I acts to increase embryo cell number while
      inhibiting heat-shock induced apoptosis. Exposure of embryos to heat shock
      reduced cell number and increased percent apoptosis, but IGF-I increased cell
      number and blocked induction of apoptosis caused by heat shock. Actions of IGF-I
      to increase cell number were blocked by treatment with the mitogen activated
      protein kinase kinase (MAPKK) inhibitor PD 98059 whereas the phosphatidylinositol
      3-kinase (PI3K) inhibitor LY 294002 had no effect. Conversely, LY 294002 but not
      PD 98059 blocked actions of IGF-I to inhibit induction of apoptosis caused by
      heat shock. The second objective was to determine whether IGF-I blocks effects of
      heat shock on development to the blastocyst stage by preventing apoptosis.
      Culture of embryos with IGF-I was effective in blocking the reduction in
      blastocyst development caused by heat shock-this action occurred even in the
      presence of LY 294002. Addition of another inhibitor of apoptosis, the caspase-3
      inhibitor z-DEVD-fmk, did not mimic the protective effects of IGF-I on blastocyst
      development. Surprisingly, IGF-I was not effective in blocking the reduction in
      blastocyst development caused by heat shock when cultured with z-DEVD-fmk. In
      conclusion, the anti-apoptotic actions of IGF-I require PI3K signaling while
      actions to promote proliferation require MAPKK signaling. Moreover, actions of
      IGF-I to allow heat-shocked embryos to continue development to the blastocyst
      stage are independent of its anti-apoptotic effects.

PMID- 16955405
TI  - Regulation of expression of the retinoic acid metabolizing enzyme CYP26A1 in
      uteri of ovariectomized mice after treatment with ovarian steroid hormones.
AB  - The retinoic acid (RA) synthesizing enzymes, retinaldehyde dehydrogenases
      (RALDH), are expressed in specific spatial and temporal patterns in uterine
      tissues during estrous cycle and early pregnancy in mice. Expression of RALDH1
      and 2 has been shown to be induced by estrogen treatment within the uterus. In
      this study, we determined the influence of progesterone and 17-ss-estradiol on
      the uterine expression of the RA-metabolizing enzyme CYP26A1 after specific time
      intervals (1, 4, 24, and 48 hr after treatment of ovariectomized mice). In a
      following experiment, we investigated the influence of gestagen (promegestone 0.3
      mg/kg body weight), estrogen (estradiol 3 microg/kg), their combination, as well
      as the antagonizing anti-progesterone hormone (RU 486 10 mg/kg) on the uterine
      expression of CYP26A1. Expression of CYP26A1 was localized using in situ
      hybridization and quantified using RT-PCR. CYP26A1 mRNA expression was strongly-
      although transiently--induced in uterine endometrial epithelial and glandular
      cells after administration of gestagen or the combination of gestagen + estrogen,
      but not by estrogen alone. These observations were confirmed by semi-quantitative
      RT-PCR experiments on whole uteri. Thus, we show that the expression of CYP26A1
      in endometrial epithelial cells is regulated by progesterone and not
      significantly influenced by co-administration of estrogen. These data indicate an
      additional level of hormonal control of endogenous RA levels in the mouse uterus,
      where its synthesis would rely on estrogen-dependent expression of RALDH enzymes,
      whereas its active metabolism would be triggered by progesterone-induced CYP26A1
      expression.

PMID- 16955406
TI  - Maturation medium supplements affect transcript level of apoptosis and cell
      survival related genes in bovine blastocysts produced in vitro.
AB  - The aim of the present study was to investigate whether protein or macromolecule
      supplements to in vitro maturation media affect transcript abundance of seven
      genes (Bax, Bcl2, Hsp70, IGF1, IGF1R, IGF2, and IGF2R) in oocytes and
      blastocysts. Cumulus-oocyte complexes aspirated from slaughterhouse ovaries were
      matured in TCM199 medium supplemented either with 10% FBS, 6% fatty acid free BSA
      (fafBSA) or 4% PVP40, then inseminated and cultured in vitro for 9 days.
      Transcript abundance analysis was carried out on immature and in vitro matured
      oocytes, as well as on blastocysts. Total RNA was isolated from pools of oocytes
      and embryos, reverse transcribed into cDNA and subjected to transcript analysis
      by real-time PCR. No transcript of IGF1 gene was detected either in oocytes or in
      blastocysts. Maturation conditions significantly affected transcript levels of
      investigated loci in blastocysts but not in matured oocytes, with one exception.
      Only relative abundance (RA) of IGF2 gene was higher in oocytes matured with
      fafBSA. Moreover, oocyte maturation with fafBSA elevated transcript abundance of
      IGF1R, IGF2, and IGF2R genes in resulting blastocysts, whereas Hsp70
      transcription was stimulated by FBS supplementation. Thus, under described
      conditions, fafBSA may be the optimal supplement to IVM medium due to higher
      transcript level of growth factor coding genes accompanied by a lower transcript
      level of Hsp70.

PMID- 16955407
TI  - Characterization of a vasa-like gene from the pacific white shrimp Litopenaeus
      vannamei and its expression during oogenesis.
AB  - The vasa gene encodes an ATP-dependent RNA helicase belonging to the DEAD-box
      family that, in many organisms, is specifically expressed in germline cells
      throughout the life cycle. In this study we first cloned Pacific white shrimp
      (Litopenaeus vannamei) partial cDNAs of two members of the DEAD-box family, one
      belonging to the vasa subfamily (Lv-Vasa) and the other to the PL10 subfamily (Lv
      PL10). Examination of their spatial expression pattern in adult tissues revealed
      that Lv-Vasa is restricted to the gonads, whereas Lv-PL10 is found in gonads as
      well as in somatic tissues. Next, we cloned the full-length shrimp vasa cDNA and
      found that Lv-Vasa encoded a protein with a DEAD-like helicase domain followed by
      a helicase superfamily C-terminal domain. In addition, Lv-Vasa encoded N-terminal
      three repeats of the C2HC-type zinc finger domain, a motif encoded by vasa genes
      of several crustaceans and several other invertebrate organisms. In situ
      hybridization of ovarian sections showed that the Lv-Vasa transcript is localized
      to the cytoplasm of the oocyte throughout oogenesis. The abundance of Lv-Vasa
      mRNA in mature oocytes suggests a maternal contribution for the developing
      embryo. It is demonstrated that the vasa homolog from L. vannamei is a gonad
      specific germline cell marker that could be exploited to enhance our
      understanding of developmental and reproductive processes in the germline of this
      economically important shrimp.

PMID- 16955408
TI  - Presence of prostate cancer metastasis correlates with lower lymph node
      reactivity.
AB  - BACKGROUND: Several reports suggest that the dissemination of neoplastic cells
      and cancer progression are associated with the generation of an immunosuppressive
      environment. METHODS: In this report, we investigated immunological effects of
      prostate cancer by comparing metastastic and non-metastatic pelvic lymph nodes
      (LNs) from 25 patients with carcinomatous involvement of LNs to the non
      metastatic LNs from 26 control patients with no metastatic involvement by
      immunohistochemistry and histological analyses. RESULTS: Our results showed a
      decreased abundance of CD20+ B lymphocytes (P = 0.031), CD38+ activated
      lymphocytes (P = 0.038), and CD68+ macrophages (P < 0.001), and less evidence of
      follicular hyperplasia (P = 0.014), sinus hyperplasia (P < 0.001), and fibrosis
      (P=0.028) in metastatic LNs comparatively to control LNs. Finally, we observed
      that metastatic LNs were significantly smaller than control LNs (P = 0.005).
      CONCLUSIONS: Our results suggest that the development of prostate cancer LN
      metastasis is accompanied with smaller LN size and decreased LN reactivity
      suggesting the development of an immununosuppressive microenvironment.

PMID- 16955409
TI  - ATRX syndrome in a girl with a heterozygous mutation in the ATRX Zn finger domain
      and a totally skewed X-inactivation pattern.
AB  - Mutations in the X-encoded gene ATRX are known to give rise to syndromic mental
      retardation in male patients whereas female carriers show preferential
      inactivation of the mutated X chromosome and appear healthy. Here, we describe a
      4-year-old girl with typical features of ATRX syndrome, carrying the recurrent
      R246C mutation of ATRX. We show that her pattern of X-inactivation is totally
      skewed and that her active X chromosome which harbors the ATRX mutation, was
      maternally inherited. To our knowledge, this is the first report of ATRX syndrome
      in a female patient. Since she was born after in vitro fertilization (IVF), we
      propose a possible link between assisted reproduction technologies (ART) and the
      unexpected X chromosome methylation pattern that we observed.

PMID- 16955410
TI  - Molecular basis of human dentin diseases.
AB  - In recent years, substantial progress has been made regarding the molecular
      etiology of human structural tooth diseases that alter dentin matrix formation.
      These diseases have been classified into two major groups with subtypes: dentin
      dysplasia (DD) types I and II and dentinogenesis imperfecta (DGI) types I-III.
      Genetic linkage studies have identified the critical loci for DD-II, DGI-II, and
      DGI-II to human chromosome 4q21. Located within the common disease loci for these
      diseases is cluster of dentin/bone genes that includes osteopontin (OPN), bone
      sialoprotein (BSP), matrix extracellular phosphoglycoprotein (MEPE), dentin
      matrix protein 1 (DMP1), and dentin sialophosphoprotein (DSPP). To date, only
      mutations within dentin sialophosphoprotein have been associated with the
      pathogenesis of dentin diseases including DGI types-II and -III and DD-II. In
      this article, we overview the recent literature related to these dentin genetic
      diseases, their clinical features, and molecular pathogenesis.

PMID- 16955411
TI  - Bifid ribs and unusual vertebral anomalies diagnosed in an anatomical specimen.
      Gorlin syndrome?
AB  - A hitherto unknown combination of multiple bifid ribs, as seen in Gorlin syndrome
      (GS), interpedicular fusion and apparent malsegmentation of vertebral laminae at
      various upper thoracic levels was found in the skeleton of a newborn infant. This
      specific combination of anomalies is also seen in the mouse open brain (opb)
      mutant. Since the genes involved in GS (Patched2) and opb (rab23) both play an
      essential role in the hedgehog signaling pathway, it is likely that the cause of
      the anomalies presented here is to be sought in impaired functioning of this
      pathway.

PMID- 16955412
TI  - Additional chromosomal abnormalities in patients with a previously detected
      abnormal karyotype, mental retardation, and dysmorphic features.
AB  - The detection of chromosomal abnormalities in patients with mental retardation
      (MR) and dysmorphic features increases with improvements of molecular cytogenetic
      methods. We report on six patients referred for detailed characterization of
      chromosomal abnormalities (four translocations, one inversion, one deletion)
      detected by conventional cytogenetics, in whom metaphase CGH revealed imbalances
      not involved in the initially detected rearrangements. The detected abnormalities
      were validated by real-time PCR. Parents were investigated by CGH in four cases.
      The genomic screening revealed interstitial deletions of 2q33.2-q34, 3p21, 4q12
      q13.1, 6q25, 13q22.2-q31.1, and 14q12. The estimated minimum sizes of the
      deletions ranged from 2.65 to 9.27 Mb. The CGH assay did not reveal imbalances
      that colocalized with the breakpoints of the inversion or the translocations. The
      deletion of 6q included ESR1, in which polymorphisms are associated with
      variation of adult height. FOXG1B, known to be involved in cortical development,
      was located in the 14q deletion. The results illustrate that whole-genome
      molecular cytogenetic analysis of phenotypically affected patients with abnormal
      conventional karyotypes may detect inapparent molecular cytogenetic abnormalities
      in patients with microscopic chromosomal abnormalities and that these data
      provide additional information of clinical importance.

PMID- 16955413
TI  - Variants in mitochondrial tRNAGlu, tRNAArg, and tRNAThr may influence the
      phenotypic manifestation of deafness-associated 12S rRNA A1555G mutation in three
      Han Chinese families with hearing loss.
AB  - We report here on the clinical, genetic, and molecular characterization of three
      Han Chinese pedigrees with aminoglycoside-induced and nonsyndromic hearing loss.
      Clinical evaluation revealed the variable phenotype of hearing loss including
      severity, age-at-onset, audiometric configuration in these subjects. Penetrances
      of hearing loss in BJ107, BJ108, and BJ109 pedigrees are 35%, 63%, and 67%,
      respectively. Mutational analysis of the complete mitochondrial genomes in these
      pedigrees showed the identical homoplasmic A1555G mutation and distinct sets of
      mitochondrial DNA (mtDNA) variants belonging to haplogroups N, F, and M,
      respectively. Of these variants, the A14693G mutation in the tRNA(Glu), the
      T15908C mutation in the tRNA(Thr), and the T10454C mutation in the tRNA(Arg) are
      of special interest as these mutations occur at positions which are highly
      evolutionarily conserved nucleotides of corresponding tRNAs. These homoplasmic
      mtDNA mutations were absent among 156 unrelated Chinese controls. The A14693G and
      T10454C mutations occur at the highly conserved bases of the TpsiC-loop of
      tRNA(Glu) and tRNA(Arg), respectively. Furthermore, the T15908C mutation in the
      tRNA(Thr) disrupts a highly conserved A-U base-pairing at the D-stem of this
      tRNA. The alteration of structure of these tRNAs by these mtDNA mutations may
      lead to a failure in tRNA metabolism, thereby causing impairment of mitochondrial
      translation. Thus, mitochondrial dysfunctions, caused by the A1555G mutation,
      would be worsened by these mtDNA mutations. Therefore, these mtDNA mutations may
      have a potential modifier role in increasing the penetrance and expressivity of
      the deafness-associated 12S rRNA A1555G mutation in those Chinese pedigrees.

PMID- 16955414
TI  - Novel mitochondrial DNA mutations associated with myopathy, cardiomyopathy, renal
      failure, and deafness.
AB  - Patients with mitochondrial disease usually manifest multisystemic dysfunction
      with a broad clinical spectrum. When the tests for common mitochondrial DNA
      (mtDNA) point mutations are negative and the mtDNA defects are still
      hypothesized, it is necessary to screen the entire mitochondrial genome for
      unknown mutations in order to confirm the diagnosis. We report an 8-year-old girl
      who had a long history of ragged-red fiber myopathy, short stature, and deafness,
      who ultimately developed renal failure and fatal cardiac dysfunction. Respiratory
      chain enzyme analysis on muscle biopsy revealed deficiency in complexes I,
      II/III, and IV. Whole mitochondrial genome sequencing analysis was performed.
      Three novel changes: homoplasmic 15458T > C and 15519T > C in cytochrome b, and a
      near homoplasmic 5783G > A in tRNA(cys), were found in the proband in various
      tissues. Her mother and asymptomatic sibling also carry the two homoplasmic
      mutations and the heteroplasmic 5783G > A mutation in blood, hair follicles, and
      buccal cells, at lower percentage. The 5783G > A mutation occurs at the T arm of
      tRNA(cys), resulting in the disruption of the stem structure, which may reduce
      the stability of the tRNA. 15458T > C changes an amino acid serine to proline at
      a conserved alpha-helix, which may force the helix to bend. These two mutations
      may have pathogenic significance. This case emphasizes the importance of pursuing
      more extensive mutational analysis of mtDNA in the absence of common mtDNA point
      mutations or large deletions, when there is a high suspicion of a mitochondrial
      disorder.

PMID- 16955415
TI  - Long contiguous stretches of homozygosity in the human genome.
AB  - Single nucleotide polymorphisms (SNPs) are the most common sequence variation in
      the human genome; they have been successfully used in mapping disease genes and
      more recently in studying population genetics and cancer genetics. In a
      population-based association study using high-density oligonucleotide arrays for
      whole-genome SNP genotyping, we discovered that in the genomes of unrelated Han
      Chinese, 34 out of 515 (6.6%) individuals contained long contiguous stretches of
      homozygosity (LCSHs), ranging in the size from 2.94 to 26.27 Mbp (10.22+/-5.95
      Mbp). Four out of four (100%) Taiwan aborigines also demonstrated this genetic
      characteristic. The number of LCSH regions increased markedly in the offspring of
      consanguineous marriages. LCSH was also detected in Caucasian samples (11/42;
      26.2%) and African American samples (2/42; 4.76%). A total of 26 LCSH regions
      were recurrently detected among Han Chinese, Taiwan aborigines, and Caucasians.
      DNA copy number determination by hybridization intensity analysis and real-time
      quantitative PCR (qPCR) excluded deletion as the cause of LCSH. Our results
      suggest that LCSHs are common in the human genome of the outbred population and
      this genetic characteristic could have a significant impact on population
      genetics and disease gene studies.

PMID- 16955416
TI  - Posttraumatic stress disorder and general health problems following myocardial
      infarction (Post-MI PTSD) among older patients: the role of personality.
AB  - OBJECTIVES: This study aimed to: (1) investigate the degree to which older MI
      patients experienced post-MI PTSD and general health problems, and to (2)
      identify the association between five personality traits, post-MI PTSD and
      general health problems among these older people. METHODS: The sample comprised
      96 older MI patients and were recruited from two general practices. They were
      interviewed using the Posttraumatic Stress Diagnostic Scale (PDS), the General
      Health Questionnaire-28 (GHQ-28) and the NEO-Five Factor Inventory (NEO-FFI). The
      control group comprised 92 older people who experienced no MI. They were assessed
      using the GHQ-28. RESULTS: The older MI patients experienced hyperarousal the
      most, followed by avoidance and re-experiencing symptoms. PDS revealed that 30%
      had full PTSD. The older patients were conscientious and agreeable individuals.
      They were also somewhat extraverted and open to experience. They also showed
      traits of neuroticism. Controlling for bypass surgery, heart failure, previous
      mental health difficulties, angina and angioplasty, regression analyses showed
      that neuroticism predicted re-experiencing and avoidance symptoms and general
      health total. Neuroticism and less agreeableness predicted hyperarousal symptoms.
      CONCLUSIONS: MI older patients could manifest PTSD symptoms and general health
      problems following their MI. Personality traits, particularly neuroticism and
      antagonism, played a role in the manifestation of these symptoms.

PMID- 16955417
TI  - Defining severe dementia with the Minimum Data Set.
AB  - BACKGROUND: Accurately defining severe dementia is important for care and
      prognosis, but is not explicitly included in the Minimum Data Set (MDS).
      OBJECTIVE: To define severe dementia using the MDS, we used data for nursing home
      residents with moderate to severe dementia. METHODS: Two cross-sectional studies
      enrolled 175 residents; 89 residents from one US Veterans Affairs nursing home,
      and 86 residents from nine Dutch nursing homes. Measurements included the
      Cognitive Performance Scale (CPS; range: 0-6), activities of daily living (ADL)
      dependency, and the Bedford Alzheimer Nursing Severity-Scale (BANS-S; range: 7
      28), a staging instrument specific for severe dementia. RESULTS: Half of the
      residents received CPS scores of 5, and their BANS-S scores varied widely. There
      was fair agreement (kappa=0.36) between severe cognitive impairment as defined by
      the CPS (scores 5 and 6) and the BANS-S (score 17 or higher). Addition of an ADL
      dependency requirement to the CPS definition improved agreement (kappa=0.75). The
      observed patterns were similar but more obvious for US residents than for Dutch
      residents. CONCLUSION: Cognitively impaired residents comprise a heterogeneous
      group with a wide variety of function. Restriction with respect to ADL dependency
      allows for distinction between moderate and severe dementia. We propose the
      following MDS-based definition of severe dementia: a CPS score of 5 or 6 with a
      minimum score of at least 10 points on the MDS ADL-Short Form.

PMID- 16955418
TI  - Doll use in care homes for people with dementia.
AB  - Dolls and teddy bears were introduced into an Elderly Mentally Ill (EMI) home as
      part of a non-pharmacological intervention. Thirteen residents from a population
      of 33 chose to use a doll and one chose a teddy bear. The impact of the toys was
      assessed on five domains over a 12-week period and the findings were generally
      positive, which was consistent with previous observations (Mackenzie et al., in
      press). The investigation also attempted to determine whether staff were able to
      predict which residents would chose a toy. In terms of the dolls, out of the 16
      residents predicted to use a doll, nine did so (56% accuracy). Despite the
      benefits outlined in this largely descriptive study, a number of problems were
      observed and some of these difficulties are outlined below.

PMID- 16955419
TI  - Patient versus informant reported quality of life in the earliest phases of
      Alzheimer's disease.
AB  - OBJECTIVES: The study investigated if patient and informant reported Quality of
      Life (QoL) differed in early Alzheimer's disease (AD). In addition, we examined
      whether anosognosia had an impact on the agreement between patient and informant
      ratings of QoL and whether anosognosia, dementia severity, depression and
      behavioural symptoms were significantly correlated to QoL in early AD. METHODS:
      From a prospective research program including newly referred patients (age >60
      years and MMSE > or = 20), 48 patients with very early AD were included. QoL was
      assessed using the QoL-AD and EQ-5D scales. Anosognosia was rated on a
      categorical scale by an examiner. MMSE, Geriatric Depression Scale, Danish Adult
      Reading Test and Frontal Behavioural Inventory were also administered. RESULTS:
      On most QoL measures patients rated their QoL higher than their informants.
      Anosognosia was not associated with QoL but significantly with an inverse impact
      on the agreement between patient and informant ratings of QoL. Self-reported QoL
      was significantly correlated to depression but not to age, dementia severity,
      behavioural symptoms or memory impairment. Informant ratings of QoL were
      significantly correlated to behavioural symptoms and informant ratings on the EQ
      5D Visual Analogue Scale were significantly correlated to patient reported
      depression. CONCLUSION: Patients with early AD generally reported higher QoL than
      their informants. This disagreement was associated with the presence of
      anosognosia. Self-reported QoL did not correlate with the MMSE score. Behavioural
      changes and depressive symptoms may be associated with low QoL.

PMID- 16955420
TI  - Differences in diagnostic subtypes among patients with late and early onset of a
      single depressive episode.
AB  - OBJECTIVE: It is unclear whether patients with late onset and patients with early
      onset present with different subtypes of depression. The aim of the study was to
      compare the prevalence of subtypes of ICD-10 single depressive episodes for
      patients with late onset (age >65 years) and patient with early onset (age < or =
      65 years) in a nationwide sample of all patients discharged from psychiatric in-
      or outpatient settings. METHOD: All patients who got a diagnosis of a single
      depressive episode in a period from 1994-2002 at the end of the first outpatient
      treatment or at the first discharge from psychiatric hospitalisation ever in
      Denmark were identified in a nationwide register. RESULTS: In total, 18.192
      patients were given a diagnosis of a single depressive episode at the first
      outpatient contact and 8.396 patients were given a diagnosis of a single
      depressive episode at the first psychiatric hospitalisation ever. Patients with
      late onset were more often women, more often presented with a severe depressive
      episode and more often with psychosis than patients with early onset, in both
      inpatient and outpatient treatment settings. No differences were found between
      patients with late and patients with early onset in the prevalence of depression
      with or without melancholic symptoms-in either of the treatment settings.
      CONCLUSIONS: Patients with a late onset first depressive episode are more often
      women and are clinically characterised by more severe depressions and a higher
      prevalence of psychosis than patients with early onset.

PMID- 16955421
TI  - Psychological treatment of late-life depression: a meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: Older meta-analyses of the effects of psychological treatments for
      depression in older adults have found that these treatments have large effects.
      However, these earlier meta-analyses also included non-randomized studies, and
      did not include newer high-quality randomized controlled trials. METHODS: We
      conducted a meta-analysis of randomized studies on psychological treatments for
      depression in older adults. RESULTS: Twenty-five studies were included, of which
      17 compared a psychological intervention to a control condition (mainly waiting
      list and care-as-usual control groups). The quality of the included studies
      varied. Psychological treatments have moderate to large effects on depression in
      older adults (standardized mean effect size d = 0.72). Heterogeneity was very
      low. No differences were found between individual, group or bibliotherapy format,
      or between cognitive behavioral therapy and other types of psychological
      treatment. The effects were comparable in studies where depression was defined
      according to diagnostic criteria, and those in which depression was measured with
      self-rating questionnaires. CONCLUSION: Although the quality of many studies was
      not optimal, the results of this meta-analysis support the results of earlier
      meta-analyses, which also included non-randomized studies. Psychological
      treatments are effective in the treatment of depression in older adults.

PMID- 16955422
TI  - Effects of TGF-beta1 and triiodothyronine on cartilage maturation: in vitro
      analysis using long-term high-density micromass cultures of chick embryonic limb
      mesenchymal cells.
AB  - Endochondral ossification is initiated by differentiation of mesenchymal cells
      into chondrocytes, which produce a cartilaginous matrix, proliferate, mature, and
      undergo hypertrophy, followed by matrix calcification, and substitution of
      cartilage by bone. A number of hormones and growth factors have been implicated
      in this process. Using in vitro, long-term, high-density, micromass cultures of
      chick embryonic mesenchyme, that recapitulate the process of chondrogenesis,
      chondrocyte maturation, and hypertrophy, we have investigated the importance of a
      balance between proliferation and apoptosis in cartilage maturation, focusing
      specifically on the effects of transforming growth factor-beta1 (TGF-beta1) and
      the thyroid hormone, triiodothyronine (T3). Our results showed that TGF-beta1
      stimulates proliferation, by week 2 of culture, and T3 inhibits proliferation by
      week 3. Cell size increases in cultures treated with T3. Collagen type X is
      expressed in all culture, and delay in matrix deposition is seen only in the
      cultures treated with TGF-beta1. T3 stimulates alkaline phosphatase activity, but
      not calcification. T3 enhances apoptosis, as seen by TUNEL staining, and
      internucleosomal DNA fragmentation. The results support the roles of T3 and TGF
      beta in cartilage maturation, i.e., TGF-beta stimulates proliferation and
      suppresses hypertrophy, while T3 stimulates hypertrophy and apoptosis.

PMID- 16955423
TI  - Mirtazapine orally disintegrating tablets in depressed nursing home residents 85
      years of age and older.
AB  - INTRODUCTION: Treatment studies of depression in the very oldest patients are
      infrequent. For these reasons, this study of mirtazapine orally disintegrating
      tablets was carried out in nursing home residents>or=85 years old with physician
      diagnosed depression. The naturalistic conditions of the study allowed us to
      include patients with cognitive impairment, concomitant medications and comorbid
      illness. METHODS: This was a subgroup analysis of nursing home residents>or=85
      years old who took part in a larger 12-week open-label trial. Patients were
      eligible if they had physician-diagnosed depression, and a Mini-Mental State Exam
      score>or=10. The physician or nurse coordinator obtained data from healthcare
      professionals in daily contact with the patient to complete the Clinical Global
      Impression (CGI) scale, a modified 16-item Hamilton Depression Scale (HAM-D), and
      the Cornell Scale for Depression in Dementia (CSDD). Treatment-emergent adverse
      events were recorded. RESULTS: Of the 50 patients enrolled at 23 sites, 72%
      completed the 12-week trial. The mean age of the participants was 89.3 years. The
      mean HAM-D score declined from 16.9 at baseline to 7.3 at endpoint (ITT, LOCF
      analysis) For the CSDD, the mean score declined from 15.1 to 7.1. The percentage
      of responders on the CGI-Improvement (CGI-I) scale increased at each assessment
      reaching 55% at endpoint. Only 10% of the patients discontinued treatment because
      of adverse events. There was a mean increase in weight of 1.32 lbs (0.6 kg) at
      day 84. CONCLUSION: Although lacking a placebo control, this naturalistic study
      suggests that mirtazapine orally disintegrating tablets were effective and well
      tolerated in this sample of depressed nursing home residents>or=85 years of age.

PMID- 16955424
TI  - The assessment of fitness to drive in people with dementia.
AB  - OBJECTIVE: To determine whether cognitive tests predict fitness to drive in
      patients with dementia. DESIGN: Two group comparison of patients with dementia
      and healthy elderly volunteers, and comparison of patients with dementia who were
      found safe to drive and those found unsafe, followed by a validation study.
      PARTICIPANTS: Forty-two people with dementia and 33 healthy elderly volunteers
      with no known memory problems who were driving. Of the 42 people with dementia 37
      were assessed on the road. A second sample of 17 people with dementia was also
      assessed on the road. MAIN MEASURES: Stroke Drivers Screening Assessment, Mini
      Mental State Examination, Salford Objective Recognition Test, Stroop Test, Test
      of Everyday Attention, Visual Object and Space Perception Battery, Behavioural
      Assessment of the Dysexecutive Syndrome, Adult Memory and Information Processing
      Battery. RESULTS: All healthy elderly volunteers were safe to drive but 10 of the
      27 patients with dementia were unsafe. Discriminant function analysis identified
      a combination of tests, which correctly classified 92% of drivers with dementia
      as safe or unsafe. Validation of this prediction on an independent sample had 59%
      accuracy using a cut-off of 0 but 88% accuracy using a cut-off of 5. CONCLUSIONS:
      Safety to drive in people with dementia could be predicted from a combination of
      six cognitive tests. These correctly identified 67% of safe drivers in a
      validation sample. This assessment could be used to identify those who need
      evaluation of their safety on the road.

PMID- 16955425
TI  - Preferences for routines in older people: associations with cognitive and
      psychological vulnerability.
AB  - OBJECTIVES: Although routine activities are important to normal functioning
      across all phases of life, their expression in older people may be associated
      with cognitive and psychological vulnerability. METHODS: The relationship between
      these variables was explored in 235 elderly French participants from the PAQUID
      cohort study. RESULTS: Cross-sectional positive associations were found between
      preferences for routines, anxiety and depression levels, and cognitive
      complaints. General cognitive decline over a three-year time span was also
      associated with a greater desire for routines at the end of this period.
      CONCLUSIONS: The progressive routinization of behaviors and activities in older
      people is discussed as a marker of affective and cognitive vulnerability, and its
      understanding has potential for improving the early detection of adaptation
      difficulties and overall care in this population.

PMID- 16955426
TI  - Response inhibition and everyday memory complaints in older adult women.
AB  - OBJECTIVE: To explore the association of executive functions to the everyday
      memory complaints of healthy older adults. METHODS: Ninety-nine community
      dwelling women aged 60 and above were administered a battery that included
      neuropsychological tests of executive functions and memory, along with self
      report measures of everyday memory complaints, depression, and anxiety. RESULTS:
      Multivariate regression analyses revealed that a measure of response inhibition
      (Stroop Color-Word) accounted for unique variance in predicting memory complaints
      above and beyond measures of episodic memory, depression, and anxiety.
      Depression, however, accounted for the largest variance in memory complaints.
      CONCLUSIONS: Higher frequency of everyday memory complaints among older adults
      was associated with decreased response inhibition independent of episodic memory
      and affective state. Further research is needed to understand the
      interrelationships among these and other predictors of everyday memory
      complaints.

PMID- 16955427
TI  - Comparison of three rating scales as outcome measures for treatment trials of
      depression in Alzheimer disease: findings from DIADS.
AB  - CONTEXT: Major depression affects about 25% of patients with Alzheimer's disease
      (AD) and has serious adverse consequences for patients as well as caregivers.
      Studies of treatments for depression in AD, like most treatment studies, depend
      on the ability of the scales used to measure outcome to detect a difference
      between the effects of treatment and control, particularly in trials conducted
      over waves. OBJECTIVE: To compare the ability of three depression scales, and
      some of their subscales, to detect the difference in the effects of drug
      (treatment) and placebo (control). DESIGN: Comparison of three scales of
      depression in terms of percent variance explained as indicated by the adjusted or
      partial eta-squared for the effect of drug versus placebo, controlling for
      baseline depression, in a randomized, placebo-controlled, parallel, 12-week,
      clinical trial of sertraline for the treatment of depression with AD. SETTING:
      University outpatient clinic. PARTICIPANTS: Forty-four patients with probable
      Alzheimer's disease and Major Depressive Episode. OUTCOME MEASURES: The Cornell
      Scale for Depression in Dementia (CSDD), the Hamilton Depression Rating Scale
      (HDRS), and the Neuropsychiatric-Inventory Mood Domains (NPI-M). RESULTS:
      Examination of the treatment effects as indicated by the partial eta-squared's
      for each scale at each wave, revealed a slight, but not significant, advantage
      for the use of the CSDD over the HDRS, and a significant advantage for the use of
      either of these over the NPI-M. Treatment effects, as reflected in the partial
      eta-squared's computed for the subscales at each wave, were significant for all
      four subscales, and were largest for the CSDD 'mood' subscale although they were
      not significantly greater than for the other subscales. CONCLUSIONS: The CSDD,
      and particularly its mood subscale, appears to be more sensitive than the HDRS,
      it's subscales or the NPI-M, for comparing drug to placebo in treating major
      depression in AD patients. Treatment effects as reflected in the partial eta
      squared's were largest on the CSDD mood subscale and increased over time. The
      pattern for the other subscales was non-monotonic over waves and resembled the
      pattern for the entire scale. Perhaps combining the CSDD two subscales obscures
      the treatment effects for the separate subscales.

PMID- 16955428
TI  - Relationship between periventricular and deep white matter lesions and depressive
      symptoms in older people. The LADIS Study.
AB  - BACKGROUND: Both types of cerebral white matter hyperintensities, periventricular
      (PVL) and deep white matter lesions (DWML) have been previously associated with
      the development of depression in older subjects. However, it remains
      controversial as to whether PVL, DWML, or both are most strongly associated with
      depression and this was the aim of the current study. METHODS: In a pan-European
      multicentre study of 626 older subjects, we examined the relationship between PVL
      and DWML, depressive symptoms (GDS quintile), cognitive status (MMSE),
      hypertension and history of stroke. RESULTS: In univariate analysis we found that
      depressive symptoms as assessed by GDS were associated with both types of white
      matter lesions (Spearman rho = 0.12 p = 0.002 for DWML and rho = 0.09 p = 0.01
      for PVL). Using ordinal logistic regression analysis the total DWML score (p =
      0.041), rather than PVL (p = 0.9) was found to predict GDS scores. CONCLUSIONS:
      DWML, but not PVL, were most strongly associated with depressive symptoms in this
      sample. As DWML (unlike PVL) are associated with vascular ischaemic damage, our
      findings are consistent with the 'vascular depression' hypothesis. Longitudinal
      studies are needed to clarify the time course of these relationships, in
      particular, whether modifying DWML alters the natural history of depression.

PMID- 16955429
TI  - The contribution of neuropsychiatric symptoms to the cost of dementia care.
AB  - OBJECTIVE: To estimate the contribution of behavioral and psychological symptoms
      of dementia (BPSD) to the costs of care. METHOD: A one-year prospective study of
      resource utilization recorded monthly by 500 caregivers of community dwelling
      patients with dementia. The effect of behavior on total, direct and indirect
      costs of care was examined. RESULTS: The total cost of care was $1,298 per month
      and there was a significant independent relationship between costs and BPSD. The
      incremental cost of a one point increase in Neuropsychiatric Inventory score was
      $30 per month (95% CI: $19-$41). CONCLUSION: BPSD contribute significantly to the
      overall costs of dementia care. Interventions targeted at BPSD may help to reduce
      the staggering societal costs of this illness.

PMID- 16955430
TI  - The association of neuroleptic sensitivity in Lewy body disease with a false
      positive clinical diagnosis of Creutzfeldt-Jakob disease.
AB  - BACKGROUND: Dementia with Lewy bodies (DLB) and Creutzfeldt-Jakob disease (CJD)
      share clinical features like cognitive decline, motor disturbances en psychiatric
      symptoms. Overlapping symptoms may cause physicians to mistake DLB for CJD.
      METHODS: Clinical data of 12 patients with autopsy-confirmed DLB who had been
      clinically suspected to suffer from CJD were analysed to investigate possible
      clinical features which led to misdiagnosis. RESULTS: There was an association in
      time between administering neuroleptics and rapid clinical deterioration in 8 out
      of 9 patients. CONCLUSION: It is suggested that the neuroleptic sensitivity in
      LBD fuelled the misdiagnosis of CJD in the presented series. Diagnostic confusion
      between CJD and DLB may have important clinical consequences and may lead to
      treatment restrictions.

PMID- 16955431
TI  - Dementia Care Mapping (DCM): initial validation of DCM 8 in UK field trials.
AB  - OBJECTIVES: This paper describes DCM 8 and reports on the initial validation
      study of DCM 8. METHODS: Between 2001-2003, a series of international expert
      working groups were established to examine various aspects of DCM with the
      intention of revising and refining it. During 2004-2005 the revised tool (DCM 8)
      was piloted in seven service settings in the UK and validated against DCM 7th
      edition. RESULTS: At a group score level, WIB scores and spread of Behavioural
      Category Codes were very similar, suggesting that group scores are comparable
      between DCM 7 and 8. Interviews with mappers and focus groups with staff teams
      suggested that DCM 8 was preferable to DCM 7th edition because of the
      clarification and simplification of codes; the addition of new codes relevant to
      person-centred care; and the replacement of Positive Events with a more
      structured recording of Personal Enhancers. CONCLUSIONS: DCM 8 appears comparable
      with DCM 7th edition in terms of data produced and is well received by mappers
      and dementia care staff.

PMID- 16955432
TI  - Nutrient intake and psychological health in an elderly Chinese population.
AB  - BACKGROUND: Associations between nutrition and cognitive impairment, and
      nutrition and depression, have been observed. Elderly people are at risk of under
      nutrition, and also have higher prevalence of cognitive impairment and
      depression. OBJECTIVE: To examine the relationship between nutrient intake and
      psychological health in the elderly, adjusting for confounding factors. SUBJECTS:
      Three thousand nine hundred and ninety-nine men and women aged 65 years and over
      living in the community, with approximately equal numbers in three age groups: 65
      69, 70-74, 75+ years. METHODS: Dietary intake was assessed using a 7-day food
      frequency questionnaire. Cognitive function was assessed by the cognitive part of
      the Community Screening Instrument for Dementia (CSID). Depression was assessed
      using the Geriatric Depression Scale (GDS). Information was also collected for
      confounding factors: demographics, educational level, socioeconomic status,
      medical history, smoking, alcohol intake, and physical activity. Logistic
      regression analyses were carried out to examine associations between lifestyle
      and dietary variables, and CSID and GDS, controlling for confounders. RESULTS:
      Both CSID and GDS scores were associated with co-morbidity, demographic and
      socioeconomic factors. Few associations between lifestyle factors and CSID score
      were observed. Dietary factors inversely associated with GDS score include total
      fat intake, vitamins A, B2, B3, C, fibre, and vegetables. In terms of nutrient
      density, iron and isoflavone intake were additional factors. CONCLUSION:
      Association exists between intake of various nutrients and psychological health
      independent of other confounding factors in the elderly population. A follow-up
      study of this cohort or interventional studies are needed to elucidate cause
      effect relationship.

PMID- 16955433
TI  - Quality of life measures for depressed and non-depressed Chinese older people.
AB  - AIM: To compare the perception of quality of life (QoL) between depressed and non
      depressed Chinese older people in Hong Kong and examined the factors that
      influence this perception. METHODS: A cross-sectional study was conducted with a
      convenience sample of 80 older people with a diagnosis of depression and 179 non
      depressed controls. RESULTS: The depressed group had a lower rating in perceived
      QoL in all aspects than the non-depressed group. Level of depression and
      functional abilities were predictors of quality of life ratings for the both
      groups and activities of daily living was the predictor of quality of life for
      the depressed group only. The study identified the subjective perception of QoL
      amongst depressed older people is significantly lower than that amongst non
      depressed older people. Depression affects the bio-psychosocial status of Chinese
      older people. This study provides insight for healthcare professionals in
      planning innovative services to meet their health needs.

PMID- 16955434
TI  - Co-morbid and socio-demographic factors associated with cognitive performance in
      an elderly community dwelling Irish population.
AB  - BACKGROUND: Epidemiological studies suggest an association between health factors
      and dementia. The impact of these factors on the cognitive performance of the
      elderly population is unclear. Possible correlates of poor cognitive performance
      in a community dwelling elderly Irish population were examined. METHODS: Subjects
      were from a sample of individuals over 65 years agreeable to interview using the
      Geriatric Mental State (GMS)-Automated Geriatric Examination for Computed
      Assisted Taxonomy (AGECAT) package conducted at the subject's home. Associations
      between patient profiles and Mini Mental State Examination (MMSE) score were
      investigated in a multivariate model. RESULTS: There were 793 subjects, 528
      (66.6%) female with mean (s.d.) age 74.8 (6.7) yrs. Mean MMSE score was 26.5
      (3.3). 169 (21.3%) were current smokers, 198 (25%) ex-smokers. Two hundred and
      twenty-four (28.3%) had a history of hypertension, 85 (10.7%) case level anxiety
      or depression, 51 (6.4%) stroke, ten0 (1.3%) epilepsy, nine (1.1%) Parkinson's
      disease and 29 (3.7%) dementia. Two hundred and fifty-five (32.2%) subjects were
      on psychotropic medications. Factors associated with MMSE score included age (p <
      or = 0.0001), diagnosis of dementia (p < or = 0.0001), socioeconomic group (p <
      or = 0.0001), education (p < or = 0.0001), previous stroke (p = 0.0013) and use
      of psychotropic medication (p = 0.03). Case level anxiety or depression (p =
      0.99), Parkinson's disease (p = 0.52), epilepsy (p = 0.26), smoking status (p =
      0.99) and hypertension (p = 0.34) were not found to be associated with cognitive
      performance. CONCLUSION: Factors associated with cognitive performance included
      age, socioeconomic group, education, previous stroke and use of psychotropic
      medication. These factors should be adjusted for in studies assessing cognition
      in this population. Stroke prevention strategies and avoidance of psychotropic
      medication may benefit cognitive performance.

PMID- 16955435
TI  - Correlates of caregiver burden for Korean elders according to cognitive and
      functional status.
AB  - BACKGROUND: Caregiver strain was investigated in a community sample of Korean
      elders with cohabiting caregivers, and factors associated with this were compared
      between groups classified by cognitive and functional impairment. METHODS: The
      study sample consisted of 484 elders and their cohabiting caregivers resident in
      Kwangju, South Korea. Caregiver burden was measured by the Zarit Burden
      Interview. Data on the elders' socio-demographics (age, gender, education, and
      religion) and clinical characteristics (cognitive function (MMSE), activities of
      daily living (IADL), depressive symptoms, alcoholism, and physical illness), and
      caregivers' socio-demographic characteristics (age, gender, education, relation
      to elders, and current employment) and caregiving environments (living area,
      alternative caregiver, number of rooms, monthly income, and social network) were
      gathered. Participants were classified into those with (n=61) or without
      cognitive impairment. The second group was classified into those with (n=68) or
      without (n=355) functional impairment. RESULTS: Caregiver strain was
      significantly associated with cognitive impairment. In the group without
      cognitive impairment, caregiver strain was significantly associated with
      participant characteristics (IADL impairment, and symptoms of depression and
      alcoholism). In those with cognitive impairment, caregiver strain was associated
      with both participant status (depressive symptoms and IADL impairment) and
      caregiver characteristics (a child caregiver, lower social support, and urban
      environment). CONCLUSIONS: Individual mental and physical health characteristics
      predict caregiver strain regardless of cognitive impairment. Caregiver
      characteristics are most important in the presence of cognitive impairment.

PMID- 16955436
TI  - A normative study of the Trail Making Test in Korean elders.
AB  - OBJECTIVE: The purpose of this study was to explore the effects of age, education
      and gender on the performance of the Trail Making Test (TMT) and provide
      normative information in Korean elders. METHODS: The TMT was administered to 997
      community-dwelling volunteers aged 60-90. People with serious neurological,
      medical and psychiatric disorders, including dementia, were excluded. RESULTS:
      Education and age had significant effects on both parts of the TMT. Gender also
      had an effect on part A of the TMT (Trail A). Based on these results, the norms
      of Trail A stratified by age (four overlapping tables), education (four strata)
      and gender, and the norms of part B of TMT (Trail B) stratified by age (four
      overlapping tables) and education (three strata). CONCLUSIONS: Age and
      educational level had a considerable influence on both Trail A and B. Our
      normative information on the Trail A will be useful in the elders with poor
      educational attainment and can be utilized for cross-cultural comparison of the
      Trail A performance. The fact that a large number of elders fail to complete
      Trail B indicates a limited applicability of Trail B in elderly population,
      particularly with poor educational background.

PMID- 16955437
TI  - Abnormal neurotransmitter metabolite levels in Alzheimer patients with a
      delirium.
AB  - BACKGROUND: Delirium is a complex neuropsychiatric syndrome with an acute onset
      and fluctuating course. Several studies have suggested the presence of disturbed
      cholinergic, dopaminergic and serotonergic pathways in delirium as well as in
      Alzheimer's disease. Abnormal concentrations of amino acids and of
      neurotransmitter metabolites have been found in plasma, platelets and
      cerebrospinal fluid of AD patients, and in plasma and CSF of patients with a
      delirium. The aim of this study was to investigate amino acid and
      neurotransmitter metabolite levels in plasma of AD patients with a concurrent
      delirium. METHODS: In a case-control study of patients suffering from Alzheimer's
      disease (AD) with concurrent delirium, we investigated the contribution of
      delirium to some biochemical parameters in blood. We compared plasma amino acid
      and neurotransmitter metabolite levels of 17 delirious AD patients with those of
      17 age- and gender-matched non-delirious AD patients and 29 age- and gender
      matched controls. RESULTS: Homovanillic acid (HVA) and 5-hydroxyindoleacetic acid
      (5-HIAA) levels were higher in delirious AD patients than in controls, but only
      HVA concentrations were higher in delirious AD patients than in non-delirious AD
      patients. CONCLUSIONS: Our findings suggest that central dopaminergic and
      serotonergic turnover are increased in AD patients with delirium and that the
      high dopaminergic turnover might reflect the consequences of delirium.

PMID- 16955438
TI  - Processing of emotionally toned pictures in dementia.
AB  - BACKGROUND: Apathy is a common symptom in dementia and is often associated with
      reduced emotional reactivity. This study examined whether reduced emotional
      reactivity can be demonstrated in dementia patients using a picture viewing task.
      METHODS: The viewing time of three different types of visual stimuli was measured
      in 24 elderly participants, half of which suffered from dementia. The
      participants had to make a target response to an emotionally neutral target
      stimulus that was intermixed with a frequently occurring non-target or
      'background' stimulus and infrequently presented emotional stimuli. All
      participants could control the presentation time of each stimulus, but one half
      of the participants were explicitly instructed to perform the task quickly.
      RESULTS: The main measure was a ratio score in which the viewing time for
      emotional stimuli was expressed relative to the viewing time for the neutral non
      target stimulus. Using this measure, the instigation of a time-pressure condition
      proved to significantly reduce the viewing time for emotional stimuli in the
      healthy subjects. Irrespective of time-pressure condition, the dementia patients
      showed a similar short viewing time for emotional stimuli as did the healthy
      subjects in the time-pressure condition. However, both dementia patients and
      healthy controls displayed longer viewing times for unpleasant than for pleasant
      stimuli. CONCLUSION: These results suggest the ability of the present task to
      reveal the simultaneous occurrence of an overall reduced interest for novel
      stimuli and an intact differential emotional reactivity to stimuli with a
      negative versus positive valence in the dementia patients.

PMID- 16955439
TI  - Risk factors for neuropsychiatric symptoms in dementia: the Cache County Study.
AB  - OBJECTIVE: To investigate the probability of individual neuropsychiatric symptoms
      in dementia patients as a function of eight risk factors. METHODS: In the Cache
      County Study, we administered the Neuropsychiatric Inventory (NPI) to 328
      dementia patients at baseline. Approximately 18 months later, we re-administered
      the NPI to 184 participants available for follow-up. Generalized estimating
      equation methods were used to model the probability of individual
      neuropsychiatric symptoms as a function of: gender, age, education, dementia type
      and severity, APOE status, time of observation, and general medical health.
      RESULTS: Women showed increased tendency toward anxiety, [odds ratio (OR) 2.22,
      95% confidence interval (CI) 1.31-3.76] and delusions (OR 2.15, CI 1.22-3.78),
      but older persons of both sexes showed less tendency toward anxiety. Dementia
      severity increased the tendency toward hallucinations and agitation (OR 2.42, CI
      1.81-3.23) and decreased risk of depression. Positive APOE epsilon4 status
      increased the tendency toward aberrant motor behavior (OR 1.84, CI 1.05-3.22).
      Among dementia diagnoses, those with Alzheimer's disease showed decreased
      tendency toward agitation (OR 0.58, CI 0.35-0.95), depression (OR 0.56, CI 0.33
      0.96) and disinhibition (OR 0.46, CI 0.24-0.88). Later time of observation
      increased risk of aberrant motor behavior and delusions, and more serious medical
      comorbidity increased risk of, agitation, irritability, disinhibition, and
      aberrant motor behavior. CONCLUSIONS: Gender, age, dementia severity, APOE
      epsilon4, dementia diagnosis, time of observation, and general medical health
      appear to influence the occurrence of individual neuropsychiatric symptoms.

PMID- 16955441
TI  - Predicting the onset of major depressive disorder and dysthymia in older adults
      with subthreshold depression: a community based study.
AB  - BACKGROUND: It is well-established that the incidence of major depressive
      disorder is increased in subjects with subthreshold depression. A new research
      area focuses on the possibilities of preventing the onset of major depressive
      disorders in subjects with subthreshold depression. An important research
      question for this research area is which subjects with subthreshold depression
      will develop a full-blown depressive disorder and which will not. METHODS: We
      selected 154 older subjects with subthreshold depression (CES-D>16) but no DSM
      mood disorder from a longitudinal study among a large population based cohort
      aged between 55 and 85 years in The Netherlands. Of these subjects, 31 (20.1%)
      developed a mood disorder (major depression and/or dysthymia) at three-year or
      six-year follow-up. We examined risk factors and individual symptoms of mood
      disorder as predictors of onset of mood disorder. RESULTS: Two variables were
      found to be significant predictors in both bivariate and multivariate analyses:
      eating problems and sleep problems. The incidence of mood disorders differed
      strongly for different subpopulations, varying from 9% (for those not having any
      of the two risk factors) to 57% (for those having both risk factors).
      CONCLUSIONS: It appears to be possible to predict to a certain degree whether a
      subject with subthreshold depression will develop a mood disorder during the
      following years.

PMID- 16955440
TI  - Recognizing and engaging depressed Chinese Americans in treatment in a primary
      care setting.
AB  - OBJECTIVES: To examine the effectiveness of depression screening and the
      Engagement Interview Protocol (EIP) in identifying and engaging in treatment
      depressed Chinese Americans in a primary care setting. METHODS: Chinese American
      patients who attended a primary care clinic between 15 September, 2004 and 14
      September, 2005 were screened for depression using the Chinese Bilingual version
      of the Patient Health Questionnaire (CB-PHQ-9). Patients who screened positive
      (CB-PHQ-9>or=15) were evaluated using the EIP to establish psychiatric diagnosis
      and to engage patients in treatment. RESULTS: Three thousand eight hundred and
      twelve patients completed the CB-PHQ-9, of which 113 (3.2%) screened positive for
      MDD. Among those screening positive, six (5.3%) had been receiving psychiatric
      treatment for depression, 57 (50%) declined to receive a psychiatric interview or
      were unable to be contacted, and 50 (44%) agreed to be interviewed with the EIP.
      Out of the 50 patients interviewed, 44 (88%) had their MDD diagnosis confirmed;
      among them, 41 (93%) agreed to receive treatment for depression and three (7%)
      declined intervention. CONCLUSIONS: Under-recognition and under-treatment of
      depressed Chinese Americans in primary care settings continue to be prevalent.
      Recognition of depression can be enhanced by using the brief CB-PHQ-9 to screen
      for depression. Half of the Chinese Americans who screened positive for MDD
      declined evaluation by a mental health professional. Most of the depressed
      Chinese Americans who were evaluated agreed to receive treatment. Enhanced
      cultural sensitivity with the use of the EIP in psychiatric assessment may have
      contributed to the success in engaging depressed Chinese Americans in treatment.

PMID- 16955442
TI  - Demonstration of cognitive decline in Parkinson's disease using the Cambridge
      Cognitive Assessment (Revised) (CAMCOG-R).
AB  - BACKGROUND: Cognitive impairment is well recognised in Parkinson's Disease (PD)
      but few studies have examined cognitive decline over time in such subjects.
      Standard clinical assessments of cognitive function, such as the MMSE, do not
      measure all cognitive domains and often have a ceiling effect. CAMCOG-R provides
      a more comprehensive cognitive assessment allowing several different domains of
      cognition to be compared. It also features the ability to test 'executive
      function'. CAMCOG-R has only been reported on one previous occasion in PD
      subjects and this is the first study to report a follow-up CAMCOG-R to assess
      cognitive decline. METHODS: In a previously published study CAMCOG-R was
      administered to a prevalent community-based population of 94 subjects with PD
      with a MMSE of 25 or above. In this subsequent study 85 of the subjects (two
      declined and seven were deceased) underwent a follow-up CAMCOG-R after a mean
      delay of 13.1 months. RESULTS: The initial, and follow-up mean total CAMCOG-R
      scores were 88.65/104 and 84.75/104 respectively, demonstrating a significant
      decline (p < 0.05). Significant cognitive decline (p < 0.05) was also seen across
      every CAMCOG-R cognitive domain and in the executive function scores.
      CONCLUSIONS: A wide range of cognitive ability was again demonstrated using
      CAMCOG-R in this PD population. The decline of 3.9 CAMCOG-R points over the 13
      month period compares to other previous studies showing an annual decline of 1.6
      CAMCOG points in normal elderly individuals and 12 CAMCOG points annually in
      those with established dementia. This study suggests that CAMCOG-R is a useful
      and appropriate tool for use in follow-up cognitive screening in PD subjects.

PMID- 16955443
TI  - Depressive symptoms in newly admitted nursing home residents.
AB  - OBJECTIVES: To study the relationship between the prevalence of depressive
      symptoms in newly admitted nursing home residents and their previous place of
      residence. METHODS: In 65 nursing homes in the Netherlands trained physicians
      assessed 562 residents (mean age 78.5, range 28-101, 64.6% female) within 10 days
      after admission. Depressive symptoms were assessed with the Minimum Data Set
      (MDS) Depression Rating Scale (DRS), and the MDS items: 'diagnosis of major or
      minor depression', 'change in depression' and 'indicators of persistent
      depressed, sad or anxious mood disorder present'. Previous place of residence was
      categorized as 'own home', 'hospital' or 'sheltered living facility'. Adjustments
      were performed for demographic and health related factors measured with the MDS.
      RESULTS: The prevalence of depressive symptoms (DRS > or = 3) for all 562
      residents was 26.9%; it was higher in residents admitted from their own home
      (34.3%) than in residents admitted from the hospital (19.7%) (p = 0.002).
      Residents who were admitted from the hospital have an adjusted Odds Ratio for
      having many depressive symptoms of 0.54 (95% CI 0.31-0.94) compared to residents
      admitted from their own home. There is, after adjustment, no statistical
      significant difference between residents admitted from their own home, or
      residents admitted from a sheltered living facility. CONCLUSIONS: Depressive
      symptoms are very prevalent in nursing homes. Residents who are admitted from
      their own home, or from a residential facility, have more depressive symptoms
      than residents admitted from the hospital. This may reflect different
      conceptualizations or different adjustment patterns for those groups. For a
      better understanding of the factors associated with nursing home depression,
      future studies in detection, prevention and management of depressive symptoms
      should start prior to or directly after admission, especially for those who have
      no prior institutional history.

PMID- 16955444
TI  - Elderly suicide attempters: characteristics and outcome.
AB  - PURPOSE: We made a descriptive survey to assess the outcome of elderly patients
      discharged from a hospital psychiatric service after a suicide attempt (rates of
      overall mortality and repeat attempts), to identify the factors that had a
      significant impact on their survival and to determine patient characteristics.
      METHODS: Fifty-nine suicide attempters over 60 years of age admitted to hospital
      between 1993 and 2000 were included in the study. Their outcome was assessed by
      questioning their attending physicians over the telephone. We traced 51 of the 59
      patients; 8 were lost to follow-up. Statistical analysis (Log Rank tests, Cox
      model) was computed to determine which factors altered the overall survival and
      the survival without further attempt. The patients sociodemographic, medical and
      psychiatric characteristics were recorded from hospital patient files. RESULTS:
      Elderly suicide attempters showed an increased mortality from suicide and natural
      causes and the risk of a repeat attempt increased in female patients with memory
      disorders. The factors altering survival were advanced age, pre-existing physical
      disability, several co-existing physical illnesses, severe physical consequences
      of the suicide attempt, history of psychiatric illness other than depression,
      memory disorders and one previous suicide attempt. The elderly suicide attempter
      was most likely to be a widowed woman suffering from social isolation, loneliness
      and depression. CONCLUSION: Elderly suicide attempters remained both physically
      and mentally vulnerable after their attempt. A repeat act represents a turning
      point in personal life progression which it is essential to detect.

PMID- 16955445
TI  - Factors related to hospitalization in elderly manic patients with early and late
      onset bipolar disorder.
AB  - OBJECTIVE: To identify factors contributing to relapse and hospitalization in
      elderly patients with bipolar disorder. METHOD: Retrospective chart review
      surveyed consecutive patients over age 65 admitted to the Johns Hopkins Hospital
      for a manic episode over a five year period (n=73). Factors precipitating index
      admission were compared in patients with early-onset bipolar disorder (<or=age
      45, n=38) and late-onset bipolar disorder (>age 45, n=35). RESULTS: The
      distribution of ages of onset of bipolar disorder was most consistent with a
      bimodal pattern with a cut-point at age 45. Early-onset patients were more likely
      to have been aggressive and threatening prior to admission (p=0.014) compared to
      late-onset patients and were more likely to have been brought to the emergency
      room on emergency petition for evaluation (p=0.028). Early-onset patients were
      also more likely to have been non-adherent with prescribed psychiatric medication
      (p=0.032). CONCLUSIONS: Relapse and rehospitalization were common among elderly
      manic patients with early-onset and late-onset bipolar disorder. Strategies which
      improve medication adherence are needed to help prevent recurring
      hospitalization.

PMID- 16955446
TI  - Drug prescription in mild cognitive impairment: the physicians' perspective in
      Italy.
AB  - OBJECTIVES: Today there are no data on the type of drugs prescribed to MCI
      patients nor the prevalence of their prescription. The aim of this study was to
      describe which drugs were prescribed in 2004 for cognitive and non cognitive
      disturbances of patients with MCI in a sizable group of Italian expert centers
      for the diagnosis and treatment of Alzheimer's disease. METHODS: Eighty-eight of
      the 314 contacted UVAs (28%) agreed to take part to the present study. The
      physicians were surveyed with a structured questionnaire assessing questions
      related to prescription of drug therapy based on their subjective judgement.
      RESULTS: Cholinesterase inhibitors are prescribed to 90% of patients with AD but,
      interestingly, to about one in four patients with MCI (27%). Gingko and
      nootropics are prescribed infrequently, but in MCI two to three times more often
      than in AD. About one in four (27%) and one in ten (9%) MCI patient are
      prescribed SSRIs and benzodiazepines, a proportion similar to that of AD (28% and
      10%), while atypical and traditional neuroleptics are virtually never used in MCI
      patients. Vitamin E is prescribed to more than half of MCI (57%) and in about
      half as many AD patients (27%). CONCLUSIONS: These data suggest that lacking
      approved or clearly effective drugs for cognitive symptoms, physicians respond
      with 'analogy treatments' and by increasing the prescription of 'accessory
      drugs'. Non cognitive symptoms in MCI are managed virtually exclusively with
      SSRIs and benzodiazepines.

PMID- 16955447
TI  - White matter lesion volumes and caudate volumes in late-life depression.
AB  - BACKGROUND: Decreased caudate volumes and increased white matter lesions (WMLs)
      are associated both with aging and late-life depression, but the relationship
      between the two is unclear. We examined the association between WML and caudate
      volume, hypothesizing there would be a negative association, which would be
      stronger for WMLs located in anterior regions. We additionally hypothesized that
      this association would be stronger in depressed subjects. METHOD: This MRI study
      included 182 elderly depressed and 64 elderly control subjects. Our imaging
      analysis procedures divided the brain into anterior and posterior halves. WML
      volume in each half was calculated, as were left and right caudate volumes. A
      statistical model incorporating WML volumes, age, total brain volume, diagnosis,
      and gender was used to examine caudate volumes. RESULTS: WML volume was
      negatively associated with total and right caudate volume. This association was
      stronger for WMLs in the anterior half of the brain. Anterior WML volume was
      additionally negatively associated with right caudate volume in depressed
      subjects, but not in controls. CONCLUSIONS: Using unadjusted levels of
      significance, WML volume is negatively associated with right caudate volume in
      both older populations, but with left caudate volume only in depressed
      individuals. When statistical corrections for multiple comparisons are used, the
      finding is limited to a negative association between WML volume and right caudate
      volume, primarily in depressed subjects. This study demonstrates one mechanism by
      which WMLs may disrupt frontostriatal circuits.

PMID- 16955448
TI  - Subjective cognitive function and decline among older adults with
      psychometrically defined amnestic MCI.
AB  - OBJECTIVE: To examine the relationship between subjective cognitive function and
      subsequent cognitive decline among individuals with psychometrically defined
      amnestic mild cognitive impairment (MCI), and to determine whether the presence
      of depressive symptoms modifies this relationship. METHOD: Fifty-five individuals
      met psychometric criteria for amnestic mild cognitive impairment (MCI). Cognitive
      decline was measured using the Mini-Mental State Examination (MMSE), which was
      administered at baseline and at follow-up two years later. Subjective cognitive
      function was examined using two different one-item memory complaints, as well as
      a scale focused on current level of cognitive function relative to past function
      and a scale focused on forgetting in specific everyday situations. RESULTS: In
      multiple regression analyses, the one-item complaint of change in memory at
      baseline predicted future cognitive decline. There was a significant interaction
      effect whereby this association was stronger in participants who endorsed fewer
      symptoms of depression. CONCLUSION: Individuals showing memory deficits
      consistent with amnestic MCI have at least some insight regarding cognitive
      decline and the extent to which subjective cognitive function is useful in
      predicting future decline may depend on what particular questions are asked as
      well as presence of depressive symptoms.

PMID- 16955449
TI  - Suicidal ideation among elderly homecare patients.
AB  - OBJECTIVES: To identify the prevalence, correlates, and one-year naturalistic
      course of suicidal ideation in a representative sample of elderly adults newly
      admitted to visiting nurse homecare. METHOD: Five hundred and thirty-nine
      participants (aged > or =65), newly initiating homecare for skilled nursing
      services, were interviewed with the Structured Clinical Interview for DSM-IV
      (SCID-IV) and measures of depression severity, medical comorbidity, functional
      status, and social support. Participants were classified as having no suicidal
      ideation in the past month, passive ideation, active ideation, or active ideation
      with poor impulse control or suicide plan. RESULTS: Fifty-seven participants
      (10.6%) reported passive and six (1.2%) reported active suicidal ideation. Higher
      depression severity, greater medical comorbidity, and lower subjective social
      support were independently associated with the presence of any level of suicidal
      ideation. At one year, suicidal ideation persisted for 36.7% of those with
      ideation at baseline, and the incidence of suicide ideation was 5.4% CONCLUSIONS:
      The high prevalence, persistence, and incidence of suicidal ideation in medically
      ill home healthcare patients underscore the relevance of this population for
      suicide prevention efforts. The clinical and psychosocial factors associated with
      suicidal ideation in this underserved, high-risk population are potentially
      modifiable, and thus useful targets for suicide prevention interventions.

PMID- 16955450
TI  - Early diagnosis of dementia in primary care: a representative eight-year follow
      up study in Lower Saxony, Germany.
AB  - OBJECTIVE: To investigate whether primary care competency in early diagnosis of
      dementia might have changed during 1993 and 2001. METHOD: By means of a
      representative follow-up survey 122 out of 170 (71.8%) family physicians (FPs) in
      Lower Saxony, Germany, were randomly assigned to two written case samples
      presenting a patient with mild cognitive impairment (case 1a vs. 1b: female vs.
      male patient) and moderate dementia (case 2a vs 2b: vascular type (VD) vs
      Alzheimer's disease (DAT)), respectively. By means of a structured face-to-face
      interview, they were asked for their diagnostic considerations. RESULTS: In
      comparison to 1993, dementia was significantly more frequently considered.
      However, there was a striking tendency in overestimating vascular aetiology and
      under-diagnosing probable DAT (case 1a/1b: DAT: 11.0% in 1993 vs 26.2% in 2001;
      VD: 2.1% in 1993 vs 17.2% in 2001). As a possible contributor to a dementia
      syndrome, concomitant medication was considered only exceptionally (case 2a/2b:
      4.4% in 1993 vs 2.5% in 2001). Physicians above 50 years of age showed a
      significantly lower early diagnostic awareness. At follow-up, the presumed
      interest in geriatric (psychiatric) topics dramatically faded from 66.9% to
      35.2%. CONCLUSIONS: Our results demonstrate a persistent need of training efforts
      aiming at the early recognition of dementia, especially of DAT, in primary care.

PMID- 16955451
TI  - Effect of a qigong exercise programme on elderly with depression.
AB  - OBJECTIVES: This report released findings of a randomized controlled trial
      conducted in Hong Kong to further our understanding of the psychosocial effects
      of qigong on elderly persons with depression. DESIGN: Eighty-two participants
      with a diagnosis of depression or obvious features of depression were recruited
      and randomly assigned into the intervention and comparison group. The
      intervention group was given a 16-week period of Qigong practice while the
      comparison group participated in a newspaper reading group with same duration and
      frequency. RESULTS: After eight weeks of qigong practice, the intervention group
      participants outstripped themselves in improvement in mood, self-efficacy and
      personal well being, and physical and social domains of self-concept when
      compared with comparison subjects. After 16 weeks of practice, the improvement
      generalized to the daily task domain of the self-concept. CONCLUSIONS: This
      report shows that regular qigong practice could relieve depression, improve self
      efficacy and personal well being among elderly persons with chronic physical
      illness and depression.

PMID- 16955452
TI  - A cross-sectional study on the health related quality of life of depressed
      Chinese older people in Shanghai.
AB  - BACKGROUND: With an increasing life expectancy, there is a rapidly growing sector
      that is aging. Depression is the most prevalent functional mental disorder of
      older population. It is estimated that about 21% of the older population in
      Shanghai are suffering from depression. AIM: This study investigated the self
      rated health related quality of life of community-dwelling older people diagnosed
      with depression in Shanghai, and to examine the relationships between this and
      mental and physical health, functional status and social support. METHODS: A
      cross-sectional survey was conducted in two community centres with a convenience
      sample of 71 participants. Measures included subjective perception of health
      related quality of life, level of depression, cognitive function, number of
      medical conditions, activities of daily living, functional abilities, and social
      support. The majority of the participants were female (n=52, 73.23%), and married
      (n=51, 71.8%). RESULTS: A higher level of depression was related to a poorer
      health related quality of life. Participants were least satisfied with their
      physical health. The level of depression, activities of daily living and
      satisfaction with social support were predictors of health related quality of
      life ratings. CONCLUSION: The study identified how depression affects the bio
      psychosocial status of Chinese older people. Findings are discussed in light of
      the socio-cultural environment in Shanghai.

PMID- 16955453
TI  - Do caregivers' experiences correspond with the concerns raised in the literature?
      Ethical issues relating to anti-dementia drugs.
AB  - BACKGROUND: The use of Cholinesterase inhibitors (ChE-Is) has raised debate in
      the literature on the ethical issues of drug treatment in dementia patients.
      These issues concern the quality of life of dementia patients and the process of
      decision-making regarding the use of ChE-Is. We interviewed caregivers of
      patients with dementia, focussing on issues of quality of life and the process of
      decision-making regarding the use of anti-dementia drugs. AIM: The aim of this
      article is to explore whether the ethical concerns raised in the literature are
      actually in line with experiences in the daily practice of dementia care.
      METHODS: Qualitative data that have been collected by semi-structured interviews
      with 12 caregivers of patients who (had) used ChE-Is. RESULTS: The results seem
      to indicate that theoretical considerations should be modified in the light of
      the reported experiences of caregivers. For example, problematic consequences of
      an early diagnosis and the creation of unreasonable hope did not appear in the
      study. Also problems concerning the rising awareness of cognitive decline were
      not found. CONCLUSION: In the interest of an ongoing ethical debate on the
      development and use of anti-dementia drugs it is important to further specify
      theoretical issues and to conduct empirical research into the practice of
      decision making and to get more insight in the perspectives of the patients using
      anti-dementia medicines themselves.

PMID- 16955454
TI  - Delirium subtype identification and the validation of the Delirium Rating Scale-
      Revised-98 (Dutch version) in hospitalized elderly patients.
AB  - BACKGROUND: Delirium is the most common acute neuropsychiatric disorder in
      hospitalized elderly. The Dutch version of the Delirium Rating Scale-Revised-98
      (DRS-R-98) appears to be a reliable method to classify delirium. The aim of this
      study was to determine the validity and reliability of the DRS-R-98 and to study
      clinical subtypes of delirium using the DRS-R-98. METHODS: Patients received the
      Dutch version of the DRS-R-98, the Mini-Mental State Examination, the Confusion
      Assessment Method, and a clinical diagnosis of delirium according to DSM-IV
      criteria, and their relatives the Informant Questionnaire Cognitive Decline in
      the Elderly. RESULTS: The DRS-R-98 validation cohort (n=65) consisted of 23
      patients with delirium, 22 patients with dementia, and 20 non-psychiatric
      comparison patients. For the delirium subtype study, a second cohort comprising
      54 delirious patients was investigated. Median DRS-R-98 scores significantly
      distinguished delirium from dementia and no psychiatric disorder. Inter-rater
      reliability (intra-class correlation 0.97) and internal consistency (Crohnbach's
      alpha 0.94) were high. Positive scores of DRS-R-98 item 4 (affect liability) and
      item 7 (motor agitation) predicted the presence of non-hypoactive delirium, with
      a specificity of 89% and a sensitivity of 57%. CONCLUSION: The results show that
      the Dutch version of the DRS-R-98 is a valid and reliable measure of delirium
      severity and distinguishes patients with delirium from patients with dementia and
      comparison patients. Furthermore, the DRS-R-98 is able to exclude hypoactive
      delirium.

PMID- 16955455
TI  - A preliminary study of the diagnostic accuracy of the Gerontological Personality
      disorders Scale (GPS).
AB  - BACKGROUND: There is still a lack of diagnostic instruments that are specifically
      developed to diagnose personality disorders in the elderly. OBJECTIVE: To develop
      a reliable and valid screening instrument to assess personality disorders in
      older adults. METHOD: The draft version of the screening instrument (52 items)
      consists of two sections: one for patients and one for informants. The diagnostic
      accuracy of the instrument has been assessed in the Netherlands in 159 elderly
      patients in an ambulatory department of geriatric psychiatry and 96 informants.
      RESULTS: In the patient section, sixteen items had a reasonable score for both
      sensitivity and specificity (approximately 70%). The internal consistency was
      moderate for habitual behavior (HAB; 7 items) and good for biographical
      information (BIO; 9 items). The test and retest reliability was moderate for HAB
      and excellent for BIO. The informant section, on the other hand, had a low score
      for sensitivity (45%) and a good score for specificity (78%). CONCLUSION: A
      specific instrument has been developed to diagnose personality disorders in older
      adults. However, further research is necessary to improve the diagnostic accuracy
      of the Gerontological Personality disorders Scale (GPS).

PMID- 16955456
TI  - Oxidative stress in asymptomatic subjects with hereditary hemochromatosis.

PMID- 16955457
TI  - Successful splenectomy in cancer-associated TTP.

PMID- 16955458
TI  - Recurrent skin reaction secondary to darbepoetin alfa for two months in a patient
      with chronic lymphocytic leukemia.

PMID- 16955459
TI  - Osteoporosis--an unusual presentation of T-cell lymphoma.

PMID- 16955460
TI  - Retinoblastoma-related geneRb2/p130 are rarely mutated in Burkitt's lymphoma from
      Brazil.
AB  - It has been suggested that alterations of cell cycle genes probably contribute to
      the pathogenesis of endemic Burkitt's lymphoma (BL) in addition to c-MYC
      translocation. Mutations disrupting the normal nuclear localization signal of the
      retinoblastoma-related gene Rb2/p130 have been documented in BL cell lines and
      primary tumors from endemic areas. The aim of this study was to investigate the
      involvement of Rb2/p130 gene in the pathogenesis of sporadic BL in Brazil. DNA
      samples from 26 pediatric BL tumors and two healthy blood donors were screened by
      PCR amplification followed by single strand conformation polymorphism analysis of
      exons 19 and 20 (B domain) and exons 21 and 22 (C-terminus), where most of the
      point mutations in the Rb2/p130 gene were identified. No abnormal band shifts
      were present in the samples analyzed. We concluded that mutations in exons 19-22
      of the Rb2/p130 are unlikely to be involved directly in the pathogenesis of
      sporadic Brazilian BL.

PMID- 16955461
TI  - Hepatitis C viral infection is not associated with Waldenstrom's
      macroglobulinemia.
AB  - While a familial predisposition may exist in up to 20% of patients with
      Waldenstrom's Macroglobulinemia (WM), the precipitating cause of this B-cell
      malignancy remains unknown in most patients. In previous studies, an association
      between hepatitis C virus (HCV) infection and WM has been suggested as
      etiological. This relationship has been the subject of debate, however, with some
      studies demonstrating increased incidence of HCV infection among WM patients and
      other studies showing no such association exists. This discordance might be
      attributable to the analytical method used, HCV antibody detection, which might
      be ineffective in patients with immunosuppression. We therefore analyzed the
      prevalence of HCV in a large population of WM patients utilizing both an HCV
      antibody detection immunoassay as well as qualitative polymerase chain reaction
      assay to directly detect HCV presence in serum samples. None of 100 randomly
      tested WM patients in this study tested positive for HCV by either analytical
      method. Our results therefore demonstrate a lack of association between HCV and
      WM.

PMID- 16955462
TI  - Pediatric ALK+ anaplastic large cell lymphoma with t(3;8)(q26.2;q24)
      translocation and c-myc rearrangement terminating in a leukemic phase.
AB  - Pediatric ALK-positive anaplastic large cell lymphoma (ALK+ ALCL) is usually
      associated with a favorable prognosis. ALK+ ALCL associated with a leukemic phase
      is uncommon, but has been associated with an aggressive clinical course and
      unfavorable prognosis. Overexpression of c-myc has been shown to be a consistent
      finding in ALK+, but not ALK-negative ALCL (ALK- ALCL), and the c-myc gene is
      considered a downstream target of deregulated ALK signaling. We describe a
      pediatric ALK+ ALCL with a leukemic phase at relapse. Similar to other rare cases
      described in the literature, it followed an aggressive clinical course despite
      multiple regimens of chemotherapy and bone marrow transplantation. Lymphoma cells
      showed aberrant ALK expression and c-myc overexpression. In addition to the
      characteristic t(2;5)(p23;q35) translocation, a t(3;8)(q26.2;q24) translocation
      was also present, and c-myc gene rearrangement was confirmed by FISH analysis.
      The findings in this case demonstrate the association of peripheral blood
      leukemic involvement and aggressive clinical course, and suggest that other
      factors, such as c-myc rearrangement, may be responsible for the aggressive
      clinical behavior in ALK+ ALCL.

PMID- 16955463
TI  - Successful self-infusion of activated prothrombin complex concentrate for
      prophylaxis in a child with a factor VIII inhibitor.
AB  - Regular self-infusion of an activated prothrombin complex concentrate (APCC) has
      been successfully introduced to a 14-year-old boy with hemophilia A. The child
      was diagnosed as a neonate, and at age 7 years, developed a high titer (127
      BU/mL) factor VIII inhibitor coincident with a protracted ankle joint bleeding.
      From age 7-10 years, he received on-demand therapy using a prothrombin complex
      concentrate (PCC), PROPLEX-ST. From age 10-14 years, he received prophylaxis with
      PROPLEX-ST, initiated after an intracranial hemorrhage and coincident anamnestic
      inhibitor response. Throughout 7-year period of PCC treatment, he experienced
      recurrent bleeding episodes. Self-prophylaxis with APCC, FEIBA VH [Anti-inhibitor
      Coagulant Complex] (50 U/kg/dose three times per week) using infusion pump was
      initiated at 14 years of age and has continued for 2 years. There were no
      bleeding, thrombotic events or other adverse events after initiation of this
      prophylaxis, and inhibitor levels decreased to 1 BU/mL. His quality of life was
      improved, particularly with respect to school. Our long observation proposes a
      well-disciplined home-based FEIBA prophylaxis in inhibitor-positive hemophiliacs.

PMID- 16955464
TI  - Late relapse of acute promyelocytic leukemia in a patient with no maintenance
      therapy.

PMID- 16955465
TI  - Quinidine-induced lupus anticoagulant, hypoprothrombinemia, and antiprothrombin
      antibodies.

PMID- 16955466
TI  - A de novo MLH1 germ line mutation in a 31-year-old colorectal cancer patient.
AB  - Hereditary nonpolyposis colorectal cancer is an autosomal dominant cancer
      predisposition syndrome caused by inherited germ line mutations in DNA mismatch
      repair genes, predominantly MSH2 and MLH1. Here we report the first proven de
      novo germ line mutation in MLH1 (c.666dupA) identified in a 31-year-old
      colorectal cancer patient with the alteration being present in a heterozygous
      state in all three germ layers and homozygously in his colon cancer. The mutation
      was absent in both biological parents and all sibs available. Despite extensive
      polymorphic marker analysis, the parental origin of c.666dupA could not be
      conclusively determined, representing either a single mutational event in a
      parental germ cell or (maternal) gonadal mosaicism. Although rare, consequential
      application of the Bethesda guidelines for genetic testing should allow the
      clinician to readily identify colorectal cancer patients below age 50 years who
      carry de novo mismatch repair gene mutations.

PMID- 16955467
TI  - Detection in primary chronic myeloid leukaemia cells of p210BCR-ABL1 in complexes
      with adaptor proteins CBL, CRKL, and GRB2.
AB  - Chronic myeloid leukemia (CML) arises as a consequence of the expression of a
      chimeric fusion protein, p210BCR-ABL1, which is localized to the cytoplasm and
      has constitutive protein tyrosine kinase activity. Extensive publications report
      that p210BCR-ABL1 complexed with multiple cytoplasmic proteins can modulate
      several cell signaling pathways. However, while altered signaling states can be
      demonstrated in primary CML material, most of the reported analytical work on
      complexed proteins has been done in cell lines expressing p210BCR-ABL1. This has
      been necessary because primary hemopoietic cell lysates contain a degradative
      activity which rapidly and permanently destroys p210BCR-ABL1, precluding accurate
      p210BCR-ABL1 quantification by Western blotting or investigation of
      coimmunoprecipitating proteins in primary cells. This degradative activity has
      proven intractable to inhibition by conventional protease inhibitors. We show
      here that the degradative activity in primary cells is associated with cell
      lysosomes and is most likely to be an acid-dependent hydrolase. By lysing primary
      hemopoietic cells at high pH, we have demonstrated substantial inhibition of the
      p210BCR-ABL1-degradative activity and now report, to the best of our knowledge,
      the first published demonstration by coimmunoprecipitation of the association
      between p210BCR-ABL1 and cytoplasmic effector proteins in primary CML material.

PMID- 16955468
TI  - Analysis of genetic abnormalities provides insights into genetic evolution of
      hyperdiploid myeloma.
AB  - Aneuploidy is ubiquitous in human cancer and is seen as whole chromosome gains
      and losses, unbalanced translocations and inversions, duplications, deletions and
      loss of heterozygosity. Within this complexity, some subgroups of aneuploid
      tumors emerge as distinct biological and clinical entities. Hyperdiploid myeloma
      (H-MM), characterized by hyperdiploid chromosome numbers because of nonrandom
      trisomies, is one such example. We undertook a comprehensive survey of the
      karyotypes of a large number of H-MM (n = 469) to describe fully genomic
      instability in these tumors, to dissect pathways of genetic evolution, and
      identify distinct subgroups based on their genetic changes. While selective
      pressure apparently favors the emergence of clones with gains of chromosomes 3,
      5, 7, 9, 11, 15, 19, and 21, a background of ongoing genomic instability results
      in gains of other chromosomes, albeit at a much lower prevalence. A deduced
      temporal analysis of these karyotypes indicates that selected gains are early
      events. Other events occurring later in the course of the disease include
      secondary chromosome translocations and monosomies. The development of these
      genetic aberrations is thus highly ordered and undoubtedly of biological
      relevance. Within this framework, we propose a model of genetic evolution in H
      MM.

PMID- 16955469
TI  - Stimulated jitter in the masseter muscle: normative values.
AB  - Nineteen healthy volunteers (median age, 25; range, 18-51 years) were enrolled in
      a study to obtain normative values for stimulated jitter in the masseter muscle.
      Axonal microstimulation was performed via a monopolar needle electrode introduced
      in the masseter 2-2.5 cm above the mandibular angle on the line connecting it
      with the lateral canthus. The recording single-fiber electromyography (SFEMG)
      electrode was inserted anteriorly in the twitching area of the muscle. The mean
      consecutive difference (MCD) values for the 426 endplates studied followed a
      distribution skewed to the left, with a minimum value of 4.3 micros, maximal 44.7
      micros, and a maximum of distribution at 11 micros. Mean pooled MCD measured 16.0
      micros, and the mean of mean MCD per study was 13.6 micros. The value of the 95th
      upper percentile for an individual fiber was 29.3 micros. We suggest an upper
      normal limit for mean MCD per study of 21 micros and upper normal limit of MCD
      for individual fibers of 30 micros. The stimulated jitter study of masseter
      muscle is easy and reliable.

PMID- 16955470
TI  - Fine-needle aspiration biopsy of a case of breast carcinoma with
      choriocarcinomatous features.
AB  - Breast disease is of great concern to patients and health care providers alike.
      Malignancies of the breast and their various presentations can pose tremendous
      challenges with respect to early diagnosis and effective treatment. Carcinoma of
      the breast may appear in several forms and produce one or more ectopic
      substances. Breast carcinomas that display choriocarcinomatous differentiation
      and produce human chorionic gonadotropin are very rare. Less than a dozen such
      cases have been described in the medical literature to date. We report a case of
      breast carcinoma with choriocarcinomatous features, which is the first to show
      immunohistochemical evidence of the expression of both estrogen receptor and
      progesterone receptor. We also discuss the cytopathologic aspects observed and
      conduct a literature review.

PMID- 16955471
TI  - Solid/trabecular variant papillary carcinoma of the thyroid: Report of three
      cases with fine-needle aspiration.

PMID- 16955472
TI  - Endometrial glandular and stromal breakdown, part 2: cytomorphology of papillary
      metaplastic changes.
AB  - Careful cytomorphologic evaluation of abnormal endometrial lesions has made
      accurate and reproducible microscopic assessment possible. Histopathology of
      patients with dysfunctional uterine bleeding due to an anovulatory cycle usually
      contain endometrial glandular and stromal breakdown (EGBD) and papillary
      metaplasia on the endometrial surface epithelium, if an appropriate sample has
      been collected. We often recognized abnormal cell clumps in the cytological
      smears with EGBD cases. They were composed of metaplastic cells, and some
      irregular small projection figures were observed from the margins of the cell
      clumps. We describe the quantitation of metaplastic clumps with irregular
      protrusions (MCIP) in endometrial endocyte samples. The current study presents
      the cytomorphological characteristics of the metaplastic changes recognized in
      EGBD cases. During a 7-yr period, 144 cases for which histopathological diagnoses
      were obtained following endometrial curettage, after collecting a direct
      endometrial sample using the endocyte. The material comprised 49 cases of normal
      proliferative endometrium (NPE) (patients aged 28-51, average 39.9), 32 cases of
      EGBD (patients aged 30-67, average 49.6), and 63 cases of endometrial hyperplasia
      without atypia (EH) (patients aged 35-65, average 47.7). The following points
      were investigated: (1) the occurrence of metaplastic cells; (2) the occurrence
      and the frequency of MCIP; and (3) the occurrence of MCIP that contains condensed
      stromal clusters. Metaplastic cells were seen in 93.8% of the EGBD cases.
      Cytomorphologic pattern identified with MCIP was 90.6%, and its frequency showed
      16.1%. The occurrence of MCIP that contain condensed stromal clusters (93.1%)
      showed a strong association in comparison with other lesions, such as NPE and EH.
      Our data appear to indicate that the appearance of MCIP with condensed stromal
      clusters originated from the papillary metaplasia, which occurred on the
      endometrial surface epithelium. The cytologic observation of those cells may be a
      useful indicator for providing the nature of EGBD endometrium.

PMID- 16955473
TI  - Role of computerized morphometric analysis in diagnosis of effusion specimens.
AB  - The present study was undertaken to compare morphometric analysis of cells in 100
      effusion samples, with unaided cytological diagnosis. All the cases in the form
      of Leishman's stained smears were subjected to computerized-interactive
      morphometry (CIM) by usage of Image analysis software. On routine cytological
      examination, 44 cases were benign, 26 were malignant, and 30 cases were placed in
      "atypical" category. On morphometry, values for mean nuclear area (MNA) and mean
      cytoplasmic area (MCA) in benign cases were found to be 58.39 +/- 12.22 microm(2)
      and 185.70 +/- 43.69 microm(2), while for malignant cases were 120.12 +/- 16.28
      microm(2) and 274.65 +/- 61.01 microm(2), respectively (P < 0.001, P < 0.001,
      highly significant). Significant differences were also noted among benign,
      atypical, and malignant cases for MNA (P < 0.001). The differences between
      atypical and malignant cases for N/C (nuclear/cytoplasmic) ratio were also found
      to be statistically significant (P < 0.001). Finally, 46 cases were found to be
      benign, 39 malignant, and 15 in the category of atypical cases. CIM helps in
      better and quicker sorting for malignant cells. MNA and N/C ratio are the most
      significant parameters in differentiating various cells in effusions. MCA
      constitutes as another useful parameter. Salient features of CIM, including their
      applications in the light of current study, are discussed.

PMID- 16955474
TI  - Cytohormonal and morphological alterations in cervicovaginal smears of
      postmenopausal women on hormone replacement therapy.
AB  - The objective of the study was to study the cytohormonal and morphological
      alterations in cervicovaginal smears associated with the use of hormone
      replacement therapy (HRT) and to assess the utility of vaginal cytology in
      determining the response to HRT. Ninety postmenopausal women (30 on estrogen
      progesterone combination (HRT) for 1 to 24 mo (user 1), 30 on estrogen therapy
      (ERT) for 1 to 44 mo (user 2), and 30 not on any hormones (nonusers)) were
      included in the cross-sectional study. Their lateral vaginal wall smears and
      cervical smears were examined for hormonal and morphological assessments,
      respectively. The smear pattern showed predominance of parabasal cells in 46.6%
      of nonusers, while none of the users had >70% parabasal cells. A high percentage
      (>70%) of intermediate cells was found in 46.6% of users and only in 16.6% of
      nonusers. A high maturation value (MV) was found in more than 75% of users but in
      only 16.6% of nonusers. The women with high MV (>50) were significantly less
      symptomatic than did nonusers. Atrophic changes were present in cervical smears
      of 14/20 (46.6%) nonusers when compared with 1/60 (1.66%) users. Atypical
      squamous cells of undetermined significance (ASC-US) were diagnosed in seven
      users and three nonusers. It persisted on follow-up in four users and one
      nonuser. Histology revealed one mild dysplasia among users. Lactobacilli were
      more frequently observed in users. The cytohormonal pattern on vaginal smears
      correlates well with the response to hormonal therapy and clinical symptoms.
      Awareness of the morphological alterations associated with the use of replacement
      hormones would enable the cytologists to reduce the false-positive diagnoses
      while evaluating postmenopausal smears.

PMID- 16955475
TI  - Role of different etiological factors in progression of cervical intraepithelial
      neoplasia.
AB  - Implication of high risk-human Papillomavirus in the process of cervical
      carcinogenesis is well documented. However, carcinogenesis in the cervix is
      recognized as multifactorial and other unknown etiological factors are also
      presumed to contribute to development of cancer. The present communication was
      aimed to investigate the role of risk factors such as age, parity, cervical
      lesions, and gynecological symptoms in the progression of the intra-epithelial
      cervical neoplasia. The study followed 571 cytologically diagnosed cases of high
      grade squamous intraepithelial lesions (HSIL) during 35 yr of cytological
      screening, which is in progress at Gynae OPD of Queen Mary's Hospital of the
      University since April 1971 and until June 2005, a total of 33,658 cervical
      smears have been cytologically evaluated. Analysis of different risk factors in
      571 HSIL cases revealed high parity coupled with increasing age to play a
      significant role in the progression of SIL. Further aggravated cervical lesions
      such as suspicious and unhealthy cervix and persistent vaginal discharge were
      found to be contributing factor in the progression of SIL. All these factors were
      predominantly seen in 35 cases of severe dysplasia that have shown progression
      from moderate dysplasia. The study indicates that women of high parity,
      especially with high age, are more prone to progression of SIL and hence this
      group needs mandatory cytological evaluation. Further adequate treatment of mild
      cervical lesions and persistent vaginal discharge is necessary to avoid the
      aggravation of the lesion/symptom and subsequent progression of dysplasia.

PMID- 16955476
TI  - Microscopic diagnosis of dysbacteriosis in stained vaginal smears in clinical
      practice.
AB  - Dysbacteriosis is a microscopical diagnosis. In women with dysbacteriosis, an
      overgrowth of coccoid bacteria and almost a complete absence of lactobacilli are
      observed in the (stained) vaginal smear. The aim of this study was to determine
      the accuracy of this microscopic diagnosis in clinical practice. The analysis
      concerned 342 consecutive cases in which the microscopy of the stained smears was
      performed by general practitioners trained in diagnosing dysbacteriosis. These
      smears were sent to the pathologist for confirmation of the microscopical
      diagnosis of the clinician. The cytological diagnoses of the pathologist,
      sometimes performed on restained slides when the quality of the staining was
      substandard, were considered as the "gold standard." In 92 of the 342 cases,
      dysbacteriosis was unequivocally established by the pathologist. Sensitivity and
      specificity of the microscopical diagnoses of the clinicians were 40% and 85%,
      respectively. There were 37 false-positive and 54 false-negative diagnoses of
      dysbacteriosis rendered by the clinicians. The most frequent reason for a false
      negative diagnosis was an excess of lactobacilli in the smear. This study shows
      that even in stained smears it is difficult for clinicians to render a correct
      evaluation of the status of the vaginal flora.

PMID- 16955477
TI  - Diagnosis of isolated tuberculous orchitis by fine-needle aspiration cytology.
AB  - An isolated tuberculous Orchitis without epididymal involvement is rare. This
      case report describes an extra pulmonary tuberculosis with exclusively testicular
      presentation. The confirmatory diagnosis of which was made on FNAC of the testis.
      A 22-year-old adult presented with unilateral testicular enlargement and scrotal
      ulcer on the same side. FNAC was performed and subsequent smear examination
      revealed epitheloid granuloma in a necrotic background. This was suggestive of
      tubercular orchitis, which was further confirmed by demonstration of very
      occasional acid fast bacilli in the smear. Isolated tuberculous orchitis is a
      rare entity; FNAC is a useful first choice of investigation. It provides a
      successful diagnosis thereby preventing unnecessary orchidectomy.

PMID- 16955478
TI  - Medullary breast carcinoma: a case report with cytological features and
      histological confirmation.
AB  - We report the case of a 83-year-old woman who presented with a left-breast lump.
      On physical examination the patient had a well-demarcated mass located in the
      upper outer quadrant of her left breast with a palpable unilateral axillary lymph
      node. Mammography and ultrasonography depicted a heterogeneous well-defined
      lesion measuring 6 cm in diameter without calcifications. Fine-needle aspiration
      cytology of the lesion was performed. Cytological examination revealed highly
      cellular smears containing large atypical cells arranged in syncytial sheets and
      intimately admixed with lymphocytes and neutrophils. The nuclear to cytoplasmic
      ratio was high in tumor cells whose nucleus exhibited coarse chromatin with one
      or more conspicuous nucleoli. The diagnosis of medullary breast carcinoma, which
      was strongly suspected by cytology, was confirmed by histological examination of
      the surgical specimen after a modified radical mastectomy with axillary
      dissection.

PMID- 16955479
TI  - Fine-needle aspiration cytology of alveolar rhabdomyosarcoma utilizing ThinPrep
      liquid-based sample and cytospin preparations: a case confirmed by FKHR break
      apart rearrangement by FISH probe.
AB  - Rhabdomyosarcoma is the most common childhood sarcoma that occurs in the soft
      tissues of the head and neck, genitourinary system, and extremities. While this
      tumor may also be seen in young adults, it is distinctly unusual to see this
      neoplasm beyond the fifth decade. The use of fluorescence in situ hybridization
      (FISH) probes on fine-needle aspiration material for chromosomal analysis to
      detect chromosomal translocations are not well established. Herein we present a
      case of metastatic alveolar rhabdomyosarcoma originating in the nasal sinus and
      recurring in the neck of an adult man 5 yr after his initial presentation. The
      ThinPrep smear demonstrated isolated malignant tumor cells similar to his
      previous histologic material. The cytologic findings of alveolar rhabdomyosarcoma
      were confirmed utilizing a dual color break apart FISH probe which identified the
      FKHR translocation on the cytospin preparation prepared from a ThinPrep vial and
      processed as a cytospin preparation. In addition to routine and immunocytologic
      staining, we demonstrate that aspirated tumor cells can be analyzed using a FISH
      probe to identify specific chromosomal abnormalities.

PMID- 16955480
TI  - Reflex high-risk human papilloma virus DNA test is useful in the triage of women
      with atypical squamous cells cannot exclude high-grade squamous intraepithelial
      lesion.
AB  - This study is aimed to investigate the role of reflex high-risk human papilloma
      virus (HPV) DNA testing as an alternative triage method to colposcopy for women
      with atypical squamous cells cannot exclude high-grade squamous intraepithelial
      lesion (ASC-H) on Papanicolaou (Pap) tests. Reflex HPV DNA testing using Hybrid
      Capture II method was carried out on 88 women with ASC-H diagnosed by Thin Prep
      Pap test. Correlation with follow-up biopsies was available on 42 of these
      patients. The reflex HPV DNA test showed an overall positive rate of 67% and
      negative rate of 33% in 88 patients with ASC-H. Using age 30 as the cut off
      point, the positive rate had increased to 83.3% (35/42) in patients 30 yr or
      younger, while the positive rate for patients older than 30 yr had decreased to
      52.2% (24/46). Follow-up colposcopic biopsy results were available in 35 of 59
      HPV-positive women, which revealed 15 (43%) high-grade squamous intraepithelial
      lesions (HSIL), 12 low-grade squamous intraepithelial lesions (LSIL), and 8
      negative for dysplasia. In 7 HPV-negative patients, the follow-up biopsies showed
      no evidence of HSIL or LSIL. Correlation between clinical risk factors and the
      HPV results demonstrated no significant differences in HPV positivity between the
      high-risk and low-risk patients. The high sensitivity (100%) and negative
      predictive rate (100%) in detecting HSIL in our study provide strong evidence
      that, instead of automatic referral to colposcopy, reflex HPV DNA testing may be
      used as an alternative triage method for women diagnosed with ASC-H on Thin Prep
      Pap test, especially for women older than 30 yr of age.

PMID- 16955481
TI  - Pulmonary Aspergillus-associated calcium oxalate crystals.

PMID- 16955482
TI  - Evidence for the presence of the type 2 corticotropin releasing factor receptor
      in the rodent cerebellum.
AB  - Corticotropin releasing factor (CRF), localized in afferent inputs to the
      cerebellum, binds to two receptors defined as the Type 1 (CRF-R1) and the Type 2
      (CRF-R2alpha). CRF-R1 has been localized to the cerebellum, as has a truncated
      isoform of CRF-R2alpha. Evidence for the presence of the full length isoform of
      CRF-R2alpha in the cerebellum is conflicting. We used RT-PCR,
      immunohistochemical, and physiologic techniques to resolve this conflict. RT-PCR
      data show low levels of CRF-R2alpha in the vermis and hemisphere of the
      cerebellum. These observations were confirmed by the Gene Expression Nervous
      System Atlas (GENSAT) database. A CRF-R2alpha antibody was used to determine the
      cellular distribution of the receptor in the cerebellum. The vast majority of the
      receptors are localized to Bergmann glial cells located throughout the
      cerebellum, as well as astrocytes in the granule cell layer. Neuronal labeling is
      present in sub-populations of Purkinje cells, Golgi cells, basket cells, and
      cerebellar nuclear neurons. Physiologic data show that urocortin II, which binds
      selectively to CRF-R2alpha, increases the firing rate of both Purkinje cells and
      nuclear neurons; this response can be blocked by the CRF-R2alpha-specific
      antagonist, antisauvagine-30. The present results confirm that CRF-R2alpha is
      present in the cerebellum and functions in circuits that modulate the firing rate
      of Purkinje cells and cerebellar nuclear neurons. A comparative analysis showed
      that the patterns of distribution of CRF-R1, CRF-R2alpha and CRF-R2alpha-tr are
      distinct. These data indicate that the CRF family of peptides modulates
      cerebellar output by binding to multiple CRF receptors.

PMID- 16955483
TI  - Liver X receptor activation decreases the severity of experimental autoimmune
      encephalomyelitis.
AB  - Agonists of liver X receptors (LXR), members of the nuclear hormone receptor
      superfamily, alter secretion of proinflammatory cytokines, suggesting potential
      antiinflammatory effects. A synthetic LXR agonist inhibited T-cell proliferation
      and cytokine release in a dose-dependent manner. Treatment of mice during
      induction of experimental autoimmune encephalomyelitis reduced clinical symptoms,
      central nervous system cellular inflammation, and major histocompatibility class
      II expression on microglia, as well as demyelination. In contrast to in vitro
      analysis, no reductions in peripheral neuroantigen specific T-cell responses were
      detected in comparing ligand and vehicle treated mice. These data suggest that
      LXR agonists play an important protective role in the regulation of T-cell
      mediated inflammatory disease of the central nervous system.

PMID- 16955484
TI  - The immunosuppressant rapamycin exacerbates neurotoxicity of Abeta peptide.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease of the central nervous
      system characterized by two major lesions: extracellular senile plaques and
      intraneuronal neurofibrillary tangles. beta-Amyloid (Abeta) is known to play a
      major role in the pathogenesis of AD. Protein synthesis and especially
      translation initiation are modulated by different factors, including the PKR/eIF2
      and the mTOR/p70S6K pathways. mRNA translation is altered in the brain of AD
      patients. Very little is known about the translation control mediated by mTOR in
      AD, although mTOR is a central regulator of translation initiation and also
      ribosome biogenesis and cell growth and proliferation. In this study, by using
      Western blotting, we show that mTOR pathway is down-regulated by Abeta treatment
      in human neuroblastoma cells, and the underlying mechanism explaining a transient
      activation of p70S6K is linked to cross-talk between mTOR and ERK1/2 at this
      kinase level. This phenomenon is associated with caspase-3 activation, and
      inhibition of mTOR by the inhibitor rapamycin enhances Abeta-induced cell death.
      Moreover, in our cell model, insulin-like growth factor-1 is able to increase
      markedly the p70S6K phosphorylation controlled by mTOR and reduces the caspase-3
      activity, but its protective effect on Abeta cell death is mediated via an mTOR
      independent pathway. These results demonstrate that mTOR plays an important role
      as a cellular survival pathway in Abeta toxicity and could represent a possible
      target for modulating Abeta toxicity.

PMID- 16955485
TI  - Functional modulation of parkin through physical interaction with SUMO-1.
AB  - Parkinson disease (PD) is the second most common neurodegenerative disorder and
      is characterized by the extensive and progressive loss of dopaminergic neurons in
      the CNS substantia nigra pars compacta region. Mutations in the parkin gene,
      which encodes for E3 ubiquitin ligase, have been implicated in autosomal
      recessive juvenile parkinsonism, an early-onset and common familial form of PD.
      Although several parkin substrates have already been identified, the molecular
      mechanism underlying the regulation of enzymatic activity of parkin has yet to be
      clarified. In a previous study, we demonstrated that RanBP2 becomes a new target
      for parkin E3 ubiquitin ligase and is processed via parkin-mediated
      ubiquitination and subsequent proteasomal degradation. RanBP2, which is localized
      in the cytoplasmic filament of the nuclear pore complex, belongs to the small
      ubiquitin-related modifier (SUMO) E3 ligase family. Here we show that parkin
      appears to bind selectively to the SUMO-1 in vivo and in vitro. Moreover, the
      physical association of SUMO-1 with parkin results in an increase in the nuclear
      transport of parkin as well as its self-ubiquitination. Our findings suggest that
      the E3 ubiquitin ligase activity of parkin and its intracellular localization may
      be modulated through the SUMO-1 association.

PMID- 16955487
TI  - Semiempirical GGA-type density functional constructed with a long-range
      dispersion correction.
AB  - A new density functional (DF) of the generalized gradient approximation (GGA)
      type for general chemistry applications termed B97-D is proposed. It is based on
      Becke's power-series ansatz from 1997 and is explicitly parameterized by
      including damped atom-pairwise dispersion corrections of the form C(6) x R(-6). A
      general computational scheme for the parameters used in this correction has been
      established and parameters for elements up to xenon and a scaling factor for the
      dispersion part for several common density functionals (BLYP, PBE, TPSS, B3LYP)
      are reported. The new functional is tested in comparison with other GGAs and the
      B3LYP hybrid functional on standard thermochemical benchmark sets, for 40
      noncovalently bound complexes, including large stacked aromatic molecules and
      group II element clusters, and for the computation of molecular geometries.
      Further cross-validation tests were performed for organometallic reactions and
      other difficult problems for standard functionals. In summary, it is found that
      B97-D belongs to one of the most accurate general purpose GGAs, reaching, for
      example for the G97/2 set of heat of formations, a mean absolute deviation of
      only 3.8 kcal mol(-1). The performance for noncovalently bound systems including
      many pure van der Waals complexes is exceptionally good, reaching on the average
      CCSD(T) accuracy. The basic strategy in the development to restrict the density
      functional description to shorter electron correlation lengths scales and to
      describe situations with medium to large interatomic distances by damped C(6) x
      R(-6) terms seems to be very successful, as demonstrated for some notoriously
      difficult reactions. As an example, for the isomerization of larger branched to
      linear alkanes, B97-D is the only DF available that yields the right sign for the
      energy difference. From a practical point of view, the new functional seems to be
      quite robust and it is thus suggested as an efficient and accurate quantum
      chemical method for large systems where dispersion forces are of general
      importance.

PMID- 16955486
TI  - Suprachiasmatic astrocytes as an interface for immune-circadian signalling.
AB  - The hypothalamic suprachiasmatic nuclei (SCN), the site of a mammalian circadian
      clock, exhibit a dense immunoreactivity for glial fibrillary acidic protein
      (GFAP), a specific marker for astrocytes. Although there is evidence of a
      circadian variation in GFAP-IR in the hamster SCN and of the participation of
      glial cells in input and output mechanisms of the clock, the role of these cells
      within the circadian system is not clearly understood. The fact that astroglia
      can express and respond to cytokines suggests that they could work as mediators
      of immune signals to the circadian system. In the present study, we have found a
      daily variation of GFAP-IR in the mouse SCN, peaking during the light phase. In
      addition, we have identified GFAP and nuclear factor-kappaB (NF-kappaB) in glial
      cells within the SCN and in primary cultures of the mouse SCN. Moreover, SCN glia
      cultures were transfected with an NF-kappaB/luc construct whose transcriptional
      activity was increased with lipopolysaccharide 2 mug/ml, tumor necrosis factor
      alpha 20 ng/ml, or interleukin-1alpha 100 ng/ml, after 12 hr of stimulation.
      These results suggest that the glial cells of the SCN can mediate input signals
      to the mouse circadian system coming from the immune system via NF-kappaB
      signaling.

PMID- 16955488
TI  - Similarity measures based on Gaussian-type promolecular electron density models:
      alignment of small rigid molecules.
AB  - Various molecular similarity measures (overlap, Coulomb, kinetic, electrostatic
      energy) and similarity indices (Carbo, Hodgkin-Richards, Kulczynski, Shape
      Tanimoto) are applied to the superposition of 3D promolecular electron density
      (PED) distributions. The original aspect of the paper lies in the consideration
      of smoothed PEDs, which allow to decrease the number of local solutions to a
      superposition problem, together with the use of the less common kinetic and
      electrostatic energy similarity measures. Results are obtained for a family of
      five rigid endothiapepsin ligands that were already considered in previous
      applications, based on graph representations of their PED. In the present work,
      it is observed that the use of smoothed PED and the kinetic similarity measure,
      together with the Kulczynski or Shape Tanimoto index, performed the best to align
      molecules of different sizes.

PMID- 16955490
TI  - Physicochemical descriptors to discriminate protein-protein interactions in
      permanent and transient complexes selected by means of machine learning
      algorithms.
AB  - Analyzing protein-protein interactions at the atomic level is critical for our
      understanding of the principles governing the interactions involved in protein
      protein recognition. For this purpose, descriptors explaining the nature of
      different protein-protein complexes are desirable. In this work, the authors
      introduced Epic Protein Interface Classification as a framework handling the
      preparation, processing, and analysis of protein-protein complexes for
      classification with machine learning algorithms. We applied four different
      machine learning algorithms: Support Vector Machines, C4.5 Decision Trees, K
      Nearest Neighbors, and Naive Bayes algorithm in combination with three feature
      selection methods, Filter (Relief F), Wrapper, and Genetic Algorithms, to extract
      discriminating features from the protein-protein complexes. To compare protein
      protein complexes to each other, the authors represented the physicochemical
      characteristics of their interfaces in four different ways, using two different
      atomic contact vectors, DrugScore pair potential vectors and SFCscore descriptor
      vectors. We classified two different datasets: (A) 172 protein-protein complexes
      comprising 96 monomers, forming contacts enforced by the crystallographic packing
      environment (crystal contacts), and 76 biologically functional homodimer
      complexes; (B) 345 protein-protein complexes containing 147 permanent complexes
      and 198 transient complexes. We were able to classify up to 94.8% of the packing
      enforced/functional and up to 93.6% of the permanent/transient complexes
      correctly. Furthermore, we were able to extract relevant features from the
      different protein-protein complexes and introduce an approach for scoring the
      importance of the extracted features.

PMID- 16955489
TI  - Tissue-engineered intervertebral disc and chondrogenesis using human nucleus
      pulposus regulated through TGF-beta1 in platelet-rich plasma.
AB  - Human intervertebral disc (IVD) degeneration often initiated from the human
      nucleus pulposus (hNP) with aging leading to IVD destruction and extracellular
      matrix (ECM) depletion. Previously, we have successfully employed transforming
      growth factor-beta1 (TGF-beta1) to promote chondrogenesis of mesenchymal
      progenitor cells (MPCs) and immortalized human mesenchymal stem cells. In this
      study, we examine the role of TGF-beta1 in platelet-rich plasma (PRP) on disc
      regeneration, including proliferation, redifferentiation, and the reconstitution
      of tissue-engineered NP. hNP cells were isolated from volunteers with different
      ages and cultured in the presence of PRP. We found that the most effective
      concentration for hNP proliferation was 1 ng/ml TGF-beta1 in PRP, which was
      further applied in the following experiments. hNP cell proliferation in all age
      groups were increased time-dependently by PRP and cell morphologies showed
      aggregation. The mRNA of Sox9, type II collagen, and aggrecan were all
      significantly upregulated by PRP through RT-PCR. Glycosaminoglycan (GAG)
      accumulation reached the highest value at day 7 and continued to day 9 culture.
      PRP promoted NP regeneration via the Smad pathway was also determined and highly
      activated p-Smad2/3 at 30 min and continuously sustained to 120 min.
      Immunostaining of type II collagen indicates that PRP participates in
      chondrogenesis of tissue-engineered NP with collagen scaffolds. We concluded that
      growth factors in PRP can effectively react as a growth factor cocktail to induce
      hNP proliferation and differentiation, and also promote tissue-engineered NP
      formation. These findings are the first to demonstrate that PRP might be a
      therapeutic candidate for prevention of disc degeneration.

PMID- 16955491
TI  - Thermal versus mechanical unfolding of ubiquitin.
AB  - The authors studied the temperature-induced unfolding of ubiquitin by all-atom
      Monte Carlo simulations. The unfolding behavior is compared with that seen in
      previous simulations of the mechanical unfolding of this protein, based on the
      same model. In mechanical unfolding, secondary-structure elements were found to
      break in a quite well-defined order. In thermal unfolding, the authors saw
      somewhat larger event-to-event fluctuations, but the unfolding pathway was still
      far from random. Two long-lived secondary-structure elements could be identified
      in the simulations. These two elements have been found experimentally to be the
      thermally most stable ones. Interestingly, one of these long-lived elements, the
      first beta-hairpin, was found to break early in the mechanical unfolding
      simulations. Their combined simulation results thus enable the authors to predict
      in detail important differences between the thermal and mechanical unfolding
      behaviors of ubiquitin.

PMID- 16955492
TI  - The pattern of Down syndrome among children in Qatar: a population-based study.
AB  - BACKGROUND: The objective of the present study was to determine the prevalence
      pattern of Down Syndrome (DS) in children <5 years of age in the State of Qatar.
      This is a retrospective descriptive study. The study was conducted in the Hamad
      General Hospital, Women's Hospital, and Rumailah Hospital (Hamad Medical
      Corporation). A total of 146 children were reported as having DS during the 6
      year period from 1 January 2000 to December 31, 2005. METHODS: The diagnostic
      classification of definitive DS was made in accordance with criteria based on the
      International Classification of Disease 10th Revision (ICD-10). The data
      collected from the medical records included sociodemographic characteristics of
      the children, genetic and family history, pedigree analysis, and clinical genetic
      examination. RESULTS: A total of 146 children were diagnosed with DS during the
      last 6-year period and the prevalence rate is 19.5 per 10,000 live births. Of
      these, 40.4% were Qataris and 59.6% were non-Qataris. DS was slightly more common
      in boys (52.7%) than girls (47.3%). Infants <1 year old had the highest frequency
      of DS (40.4%), followed by children (1-2) years (26%). The most common
      abnormality was regular trisomy (98%). Also, one-half of the studied children had
      congenital heart problems (51.7%). There is a significant relationship between DS
      and maternal age as reported by other studies in other countries. CONCLUSION: The
      identification of specific types of chromosomal abnormalities in DS children is
      important as it enables clinicians to accurately counsel the parent regarding the
      recurrence risk and available options.

PMID- 16955493
TI  - Exposure to 5-bromo-2'-deoxyuridine induces oxidative stress and activator
      protein-1 DNA binding activity in the embryo.
AB  - BACKGROUND: During organogenesis the embryo is highly sensitive to oxidative
      stress. We hypothesize that oxidative stress and activation of a redox-sensitive
      transcription factor, activator protein-1 (AP-1), are early indicators of
      embryonic stress in response to a teratogenic insult. 5-Bromo-2'-deoxyuridine
      (BrdU) was chosen as a model teratogen to test this hypothesis; BrdU is a
      thymidine analog that is incorporated into replicating DNA. METHODS: Timed
      pregnant CD1 mice were given vehicle or BrdU (400, 600, 800, or 1000 mg of
      BrdU/kg of body weight) on gestation day 9 (GD 9). Oxidative stress, assessed as
      the ratio of glutathione disulfide (GSSG) to reduced glutathione (GSH), and AP-1
      DNA binding activity (c-Fos- and c-Jun-dependent DNA binding) were measured in
      the maternal livers and embryos 0.5, 3, and 6 hr after treatment. External and
      skeletal malformations were assessed on GD 18. N-acetylcysteine, a glutathione
      precursor, was coadministered with BrdU to further explore the relationship
      between teratogenicity and redox homeostasis. RESULTS: BrdU exposure produced a
      dose-dependent increase in skeletal malformations, which included polydactyly,
      and delayed ossification of the sternebrae and vertebrae. Exposure to teratogenic
      doses of BrdU depleted GSH concentrations and increased oxidative stress, as
      assessed by the GSSG:GSH ratio, in both maternal livers and embryos. While c-Jun
      DNA binding activity in embryos was not affected, c-Fos DNA binding activity was
      elevated significantly 3 hr after BrdU exposure. Coadministration of N
      acetylcysteine decreased the skeletal malformations and AP-1 DNA binding activity
      induced by BrdU. CONCLUSIONS: BrdU exposure induced an embryonic stress response
      manifested as an increase in oxidative stress and AP-1 DNA binding activity;
      these data support the hypothesis that disturbances in redox homeostasis mediate
      the response of the conceptus to a teratogenic insult.

PMID- 16955494
TI  - Quality and content of abstracts in papers reporting about drug exposures during
      pregnancy.
AB  - BACKGROUND: Most clinicians read only the abstract of papers in scientific
      journals. Therefore, it is very important that abstracts contain as much
      information as possible, to summarize the data succinctly. Our objectives were to
      evaluate the quality of information in abstracts reporting human fetal outcomes
      following drug exposure during pregnancy. METHODS: We developed quality criteria
      based on previous work, modifying them for use with pregnancy outcomes. Quality
      scores were calculated as present/absent for all of the equally weighted
      criteria, then expressed as percentages (present/[present + absent]). We examined
      a random sample of 100 abstracts obtained through searches of MEDLINE, EMBASE,
      and the Web of Science databases from 1990 to 2005. Average quality scores were
      compared across designs (cohort, case-control, meta-analysis, and mixed design)
      Using Kruskal-Wallis ANOVA and structured/unstructured formats using Student's t
      test. RESULTS: The overall average quality was 59.2% +/- 14% (median, 61.5%;
      range, 15.4-83.3%). Quality was not significantly different across designs (P =
      .16) or between structured and unstructured abstracts (P = .44). Quality scores
      increased over time (Rho = 0.23, P = .02). Most frequently absent were baseline
      risk (94%), drug dose (91%), nonsignificant P values (72%), confounders (69%),
      significant P values (57%), and risk difference (48%). CONCLUSIONS: Abstracts
      provide insufficient information, particularly baseline risk values, for readers
      to make evidence-based decisions regarding drug use during pregnancy. Efforts
      need to be made to improve the quality of abstracts and include critical
      information such as baseline risk.

PMID- 16955495
TI  - Maternal severe migraine and risk of congenital limb deficiencies.
AB  - BACKGROUND: Migraines occurs frequently during pregnancy; however, there are no
      published data on their possible teratogenic potential in a controlled
      epidemiological study. Therefore, we examined the risk of congenital
      abnormalities in infants born to women who had migraines and other headaches
      during pregnancy. METHODS: Between 1980 and 1996, the Hungarian Case-Control
      Surveillance of Congenital Abnormalities evaluated 22,843 cases (newborns or
      fetuses) with congenital abnormalities, 38,151 control newborn infants without
      any abnormalities, and 834 malformed controls with Down syndrome. RESULTS:
      Migraines anytime during pregnancy occurred in 565 (2.5%) mothers of the case
      group compared with 713 (1.9%) mothers in the control group (crude prevalence
      odds ratio [POR], 1.3; 95% confidence interval [CI], 1.2-1.5) and 24 (2.9%)
      pregnant women in the malformed control group (crude POR, 0.9; 95% CI, 0.6-1.3)
      The mothers of 247 cases, 533 controls, and 21 malformed controls had severe
      migraines during the second and/or third months of pregnancy. There was only 1
      congenital abnormality group: limb deficiencies, which had a higher rate of
      maternal migraines during the second and third months of pregnancy both at the
      comparison of cases and matched controls (adjusted POR, 2.5; 95% CI, 1.1-5.8) and
      of cases and malformed controls (adjusted POR, 1.7; 95% CI, 1.3-3.0). There was
      no association between other headaches and different congenital abnormalities at
      the comparison of cases and controls. CONCLUSIONS: Our data showed that maternal
      severe migraines during the second and/or third months of pregnancy were
      associated with an increased risk of congenital limb deficiencies. A similar
      association was not detected between congenital anomalies and other headaches
      during pregnancy. Our study was not based on a prior hypothesis; therefore, these
      data can be considered only as a signal that needs confirmation by independent
      data sets.

PMID- 16955496
TI  - Trends in histology laboratory teaching in United States medical schools.
AB  - Owing to competition for faculty time among the three major missions of today's
      academic medical centers, as well as the rapid development of computer-based
      instructional technologies, laboratory instruction in medical schools in the
      United States has been undergoing dramatic change. In order to determine recent
      trends in histology laboratory instruction at U.S. medical schools, a detailed
      Web survey was administered to histology course directors, with about two-thirds
      of schools responding. The survey was designed to identify trends in the number
      of hours of histology laboratory instruction that each medical student receives,
      the amount of faculty effort devoted to histology laboratory instruction, and the
      use of various computer-based technologies (including virtual microscopy and
      virtual slides) in histology laboratory instruction. Consistent with the long
      term trend of declining total laboratory teaching hours in U.S. medical schools,
      there is an ongoing reduction in the number of hours of faculty-directed
      histology laboratory instruction that each medical student receives, with a
      concomitant reduction in hours of faculty time devoted to histology laboratory
      instruction. In terms of the tools used in the histology laboratory, there has
      been a dramatic increase in the use of various forms of computer-aided
      instruction (including virtual slides). The large increase in the number of
      schools using computer-aided instruction has not been accompanied by an
      equivalent decrease in the number of schools that utilize microscopes and glass
      slides. Rather, the clear trend has been toward a blending of the new computer
      based instructional technologies with the long-standing use of microscopes and
      glass slides.

PMID- 16955497
TI  - Functional morphology of the first cervical vertebra in humans and nonhuman
      primates.
AB  - The cervical vertebral column bears or balances the weight of the head supported
      by the nuchal muscles that partly originate from the cervical vertebrae. The
      position of the head relative to the vertebral column, and consequently
      locomotion and posture behavior, could thus be associated with the form of the
      cervical vertebrae. In spite of this assumption and some empirical indications
      along these lines, primate vertebral morphologies have been reported to be very
      similar and not clearly related to locomotion. We therefore study the
      relationship between the morphology of the first cervical vertebra, the atlas,
      and the locomotion pattern within primates using a geometric morphometric
      approach. Our analysis is based on a total of 116 vertebrae of adult Homo
      sapiens, Gorilla gorilla, Pan troglodytes, Pongo pygmaeus, Hylobates lar, Macaca
      mulatta, Papio hamadryas, Ateles geoffroyi, and Alouatta palliata. On each atlas,
      56 landmarks were digitized and superimposed by Procrustes registration. The
      resulting shape variables were analyzed by principal component analysis,
      multivariate regression, and partial least-squares analysis. We found that the
      nine primate species differ clearly in their atlas morphology and that allometric
      shape change is distinct between the nonhuman primates and Homo sapiens. We could
      further identify morphological features that relate to the species' locomotion
      pattern. Human atlas shape, however, cannot be predicted by an extrapolation of
      the nonhuman primate model. This implies that either the primate atlas is
      generalized enough to allow bipedal locomotion or else the human atlas morphology
      is a unique adaptation different from that in the more orthograde nonhuman
      primates.

PMID- 16955498
TI  - Diffusion of innovations: anatomical informatics and iPods.
AB  - Over the course of many centuries, evolving scientific methods and technologies
      have advanced the study of anatomy. More recently, such dissemination of
      innovations has been formally studied in multidisciplinary psychosocial contexts,
      yielding useful knowledge about underlying principles and processes. We review
      these precepts and show how diffusion of innovations theory and principles apply
      to the development and dissemination of anatomical information methods and
      resources. We consider the factors affecting the late-20th-century dissemination
      of personal computers and World Wide Web hypermedia into widespread use in
      anatomical research and instruction. We report on the results of a small
      experiment in applied diffusion, the development and Internet-based distribution
      of learning resources for a popular, widely distributed personal media player.
      With these wearable microcomputer devices already in use by a variety of
      students, new opportunities exist for widespread dissemination of anatomical
      information. The continuing evolution of wearable computing devices underscores
      the need for maintaining anatomical information transportability via standardized
      data formats.

PMID- 16955499
TI  - Damage to the human cerebellum from prenatal alcohol exposure: the anatomy of a
      simple biometrical explanation.
AB  - Since 1973, it has become clear that exposure of otherwise normal human fetuses
      to high levels of alcohol damages a substantial number of the exposed brains in a
      wide variety of ways nowadays referred to collectively as the fetal alcohol
      spectrum disorders (FASDs). Averages of images and measurements of brains with
      these disorders are quantitatively different from normal, and the cerebellum is
      one of the structures at which differences are typically noted. The present
      article extends these techniques to a simple, practical, and enlightening
      detection rule for fetal alcohol damage in adolescents and adults known to have
      been heavily exposed. The data arise from 180 clinical MR brain images (half of
      adolescents, half of adults; half male, half female; one-third each fetal alcohol
      syndrome, fetal alcohol effects, and unexposed). The 180 cerebellums were
      represented by 328-semilandmark triangulations covering most of the cerebellar
      surface. Statistical analysis exploited the now-conventional methods of
      Procrustes analysis in three dimensions, along with a recent extension to
      incorporate size information explicitly. If we reduce the data complexity even
      further, to just 23 points along the silhouette of the cerebellum as viewed from
      above along the aqueductal axis, the analysis becomes more precise. Now a single
      multivariate summary score, very strongly correlated with size, supports a
      discrimination (diagnosed vs. unexposed) with about 75% accuracy. About one
      quarter of our FASD sample overlaps with the central range of the unexposed in
      the distribution of this size-based score, with the other three-quarters
      distinctly showing cerebellar damage. The finding, which corresponds quite
      closely to the fundamental finding of cerebellar hypoplasia in animal
      experiments, bears implications for fetal alcohol epidemiology, for geometric
      morphometrics, and for the geometric complexity of useful data structures derived
      from clinical brain imaging.

PMID- 16955501
TI  - Further evidence of association between mutations in FGFR2 and syndromic
      craniosynostosis with sacrococcygeal eversion.
AB  - BACKGROUND: Pfeiffer syndrome (PS; OMIM #101600) is an autosomal dominant
      disorder characterized by craniosynostosis, midface hypoplasia, broad thumbs,
      brachydactyly, broad great toes, and variable syndactyly. CASE: We report a case
      of PS (type 3) with tracheal and visceral involvement and sacrococcygeal
      eversion. The patient shows facial dysmorphism with macrocephaly, dolichocephaly,
      and trigonocephaly, and an asymmetric skull, bilateral and severe exophthalmia
      with shallow orbits and ocular hypertelorism, downslanting palpebral fissures,
      constant strabismus, short anterior cranial base, and midface hypoplasia.
      CONCLUSIONS: Molecular analysis of the FGFR2 gene in this patient revealed a
      point mutation (c.890G>C NM_000141). This mutation leads to the substitution of
      the residue tryptophan at position 290 to cysteine in the protein (p.Try290Cys).
      These data reinforce the hypothesis that the p.Trp290Cys mutation is more often
      associated with a severe and poor prognosis of PS. Furthermore they suggest that
      the presence of sacrococcygeal defects is not associated with any specific FGFR2
      mutation.

PMID- 16955502
TI  - Periconceptional health and lifestyle factors of both parents affect the risk of
      live-born children with orofacial clefts.
AB  - BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (CL/P) or cleft
      palate only (CPO) are orofacial clefts and have a multifactorial etiology. The
      identification of amendable parental risk factors may contribute to a reduced
      occurrence of these malformations in the future. METHODS: Standardized
      demographic and periconceptional exposure data from 284 parents of a child with
      CL/P, 66 parents of a child with a CPO and 222 parents of a child without
      congenital malformations were collected at approximately 24 months after the
      periconceptional period of the index child. Univariate and multivariate logistic
      regression analyses were used to estimate relative risks by odds ratios (ORs) and
      95% confidence intervals (95% CIs). RESULTS: Univariate results suggest that low
      parental education, periconceptional maternal medication use and illnesses,
      paternal smoking, and first-trimester maternal common cold increased CL/P risk.
      Pregnancy planning and periconceptional folic acid supplementation, however,
      reduced CL/P risk by approximately 50% (OR, 0.5; 95% CI, 0.3-0.8) and 40% (OR,
      0.6; 95% CI, 0.4-0.9), respectively. Mostly comparable results were obtained for
      CPO. Being a boy (OR, 2.0; 95% CI, 1.4-3.0), folic acid supplementation (OR, 0.6;
      95% CI, 0.4-0.9), and low paternal education (OR, 1.6; 95% CI, 1.0-2.3) mainly
      determined CL/P in the multivariate analyses, compared to low paternal (OR, 4.5;
      95% CI, 2.1-9.4) and maternal medication use (OR, 2.0; 95% CI, 1.0-4.0) for CPO.
      CONCLUSIONS: Preconceptional counseling for orofacial cleft risk assessment
      should pay attention to maternal medication use, periconceptional folic acid
      supplementation, and exposures of the father. These determinants can be amended,
      thereby modifying orofacial cleft risk.

PMID- 16955503
TI  - Engineering eukaryotic signal transduction with RNAi: enhancing Drosophila S2
      cell growth and recombinant protein synthesis via silencing of TSC1.
AB  - RNAi has been useful in the study of biochemical pathways, but has not been
      widely used as a tool in metabolic engineering. The work described here makes use
      of double-stranded RNA (dsRNA) for the post-transcriptional gene silencing of
      TSC1 in Drosophila S2 cells. TSC1 downregulates the insulin-mediated signal
      transduction pathway, and serves as a metabolic control to guard against cellular
      overproliferation and tumorogenesis in both flies and mammals. By silencing TSC1
      with in vitro-synthesized dsRNA, we have created a tunable and specific metabolic
      "throttle" that, like insulin, apparently increases the specific growth rate of
      S2 cells in a dose-dependent manner. This "throttle," augments the benefits of
      insulin addition while apparently avoiding deleterious and pleiotropic effects
      which can lead to lysis. During the period wherein dsRNA was active, cell growth
      rate was increased by 11% by the addition of 15 microg/mL dsTSC1 and by over 20%
      by the addition of 30 microg/mL dsTSC1. Additionally, synthesis of recombinant
      green fluorescent protein (GFP) was increased nearly 50% in a stable S2 cell line
      inducibly expressing GFP. Accordingly, we have "tuned" a normally tumorogenic
      pathway in animals into an advantage for both growth and recombinant product
      synthesis in cell culture. Potential applications for improving eukaryotic cell
      culture are anticipated.

PMID- 16955504
TI  - Selective use of sentinel lymph node surgery during prophylactic mastectomy.
AB  - BACKGROUND: Patients with invasive cancer identified at the time of prophylactic
      mastectomy (PM) will require axillary lymph node dissection for staging;
      therefore, many surgeons advocate sentinel lymph node (SLN) surgery at the time
      of PM. The current study investigates the invasive cancer rate in PM and
      evaluates factors associated with invasive cancer to guide SLN surgery use.
      METHODS: Patients undergoing PM at the M. D. Anderson Cancer Center between
      January 2000 and July 2005 were identified from a prospective database. Clinical,
      radiographic, and pathologic data were collected. RESULTS: A total of 409
      patients (436 PM cases) were identified; 382 underwent contralateral PM (CPM) and
      27 underwent bilateral PM (BPM). Cancer was identified in 22 of 436 PM cases
      (5%). Of these, 14 patients (64%) had ductal carcinoma in situ (DCIS). Only 8
      patients (1.8%) had invasive cancer, with a mean tumor size of 5 mm (range, 2-9
      mm). There was no difference in the occult cancer rate between CPM and BPM. No
      cases of invasive cancer were identified in the 23 patients with BRCA mutations.
      Significantly increased risk of invasive cancer in the PM breast was seen in
      postmenopausal patients (3.7%; P = .007), patients age >60 years (7.5%; P =
      .008), and patients with history of invasive lobular carcinoma (9.7%; P = .0002)
      or lobular carcinoma in situ (LCIS) (7.7%; P = .008). CONCLUSIONS: The frequency
      of cancer in PM is very low and the majority represents DCIS. Therefore, routine
      use of SLN surgery in all patients undergoing PM is not warranted. However,
      patients at higher risk for whom SLN surgery should be considered include older
      women and patients with a history of lobular cancer or LCIS.

PMID- 16955505
TI  - Treatment outcome in young adults and children >10 years of age with acute
      lymphoblastic leukemia in Sweden: a comparison between a pediatric protocol and
      an adult protocol.
AB  - BACKGROUND: Several studies have reported a more favorable outcome for teenagers
      and young adults with acute lymphoblastic leukemia (ALL) when they were treated
      in pediatric oncology departments compared with adult hematology departments.
      However, biased risk grouping and high treatment-related mortality have hampered
      some of those comparisons. METHODS: In Sweden during the 1990s, adolescents with
      ALL were treated in a pediatric oncology unit or in an adult hematologic unit,
      depending on the initial referral. In the current national, comparative,
      retrospective study, patients with ALL aged 10 years to 40 years who were treated
      either according to the Nordic Society of Pediatric Hematology and Oncology
      (NOPHO) ALL protocol (1992-2000) (NOPHO-92 protocol) or according to the Swedish
      Adult ALL Group protocol (1994-2000) (Adult protocol) were included. None of the
      protocols had age as a high-risk criterion. RESULTS: In total, 243 patients with
      B-precursor and T-cell ALL were treated according to the protocols. There was a
      significant difference in the remission rate between the NOPHO-92 protocol (99%;
      n = 144 patients) and the Adult protocol (90%; n = 99 patients; P < .01), and the
      event-free survival (EFS) was also superior for the NOPHO-92 protocol compared
      with the Adult protocol (P < .01). However, EFS was higher for patients aged 15
      years to 25 years compared with patients aged 26 years to 40 years within the
      Adult protocol group (P = .01). The treatment protocol itself was identified as
      an independent risk factor. CONCLUSIONS: The NOPHO-92 protocol resulted in a
      better outcome than the Adult protocol; therefore, adolescents may benefit from
      the pediatric protocol treatment strategy. Prospective trials are warranted to
      determine whether young adults would benefit from similar treatment.

PMID- 16955507
TI  - Gliomatosis cerebri: 20 years of experience at the Children's Hospital of
      Philadelphia.
AB  - BACKGROUND: Gliomatosis cerebri (GC) is a rare and typically fatal glial neoplasm
      of the central nervous system. In this report, the authors describe the largest
      cohort of children to date with GC and explore relations between potential
      prognostic factors, treatment, and survival. METHODS: Imaging, pathologic, and
      outcome data were reviewed from 13 patients who were diagnosed with GC and were
      treated at the Children's Hospital of Philadelphia (CHOP) between 1982 and 2005.
      All patients had GC confirmed by biopsy. Twelve patients received cranial
      irradiation, and 8 of those patients received adjuvant chemotherapy. A single
      patient age 1 year received chemotherapy alone. A review of the literature
      identified 51 pediatric patients with GC. RESULTS: The progression-free survival
      rate in this study was 13% (range, 1.5-43 months), and the overall survival (OS)
      rate was 64% (range, 6.5-67 months) at 2 years. OS was significantly shorter for
      patients who presented in the first decade of life (P = .04). The time to
      progression was prolonged significantly for patients who had no evidence of tumor
      enhancement on imaging studies (P = .03). When survival data from patients
      reported in the literature were combined with the CHOP cohort, treatment
      prolonged OS significantly (P = .003). CONCLUSIONS: The outcome of pediatric
      patients with GC was extremely poor; however, the current results indicated that
      treatment may prolong OS. Age < 10 years and contrast enhancement on magnetic
      resonance imaging studies at diagnosis may be risk factors for shorter survival
      in pediatric patients with GC.

PMID- 16955506
TI  - Squamous cell carcinoma of the lung compared with other histotypes shows higher
      messenger RNA and protein levels for thymidylate synthase.
AB  - BACKGROUND: In patients with cancer, one of the main mechanism of resistance to
      antimetabolite drugs is related to higher levels of thymidylate synthase (TS)
      activity. METHODS: To investigate the association between TS expression and
      histopathologic data, 56 resection specimens from patients with nonsmall cell
      lung carcinoma (NSCLC) were collected consecutively. TS messenger RNA (mRNA) was
      evaluated in tumor specimens by using real-time polymerase chain reaction (PCR)
      analysis; protein expression was evaluated by using immunohistochemistry (IHC) in
      formalin-fixed, paraffin-embedded (FFPE) specimens; and the analysis of TS
      transcriptional regulation activity was performed by using real-time PCR analysis
      in snap-frozen normal and tumor specimens. RESULTS: The amplification of the TS
      gene from FFPE tissues was obtained from all samples, with a median level (unit
      less ratio) of 1.45 (range, 0.34-5.24); whereas positive TS status at IHC (>10%
      positive cells) was detected in 56% of samples. It is noteworthy that TS
      expression was significantly higher in squamous cell carcinoma compared with
      adenocarcinoma when both mRNA levels (2.17 vs. 1.16; P < .0001) and protein
      levels (P = .0269) were considered in FFPE specimens, and a strong association
      was observed between mRNA and protein expression (P = .00017). Moreover, higher
      TS levels were observed in high-grade tumors (P = .0389 and P = .0068 for mRNA
      and protein quantification, respectively). The analysis in snap-frozen samples
      revealed that the TS gene was up-regulated strongly in tumors (P = 3.8 x 10(
      12)), and an 8-fold increase (as a cut-off value) in the TS mRNA ratio between
      tumor and corresponding normal tissue was detected in 32 of 56 patients (57%)
      bearing preferentially squamous cell tumors (P = .0022) and high-grade tumors (P
      < .001). CONCLUSIONS: Data from the current study consistently indicated higher
      TS expression levels in squamous cell and in high-grade carcinomas. This
      information may be useful in selecting which patients with NSCLC should receive
      treatment with TS-inhibiting agents.

PMID- 16955509
TI  - The significance of neuroendocrine differentiation in adenocarcinoma of the
      esophagus and esophagogastric junction after preoperative chemoradiation.
AB  - BACKGROUND: Esophageal and esophagogastric junction (EGJ) adenocarcinomas
      frequently have neuroendocrine (NE) differentiation, but the significance of NE
      differentiation in patients who have undergone preoperative chemoradiation and
      resection remains unclear. METHODS: The authors evaluated the presence of NE
      differentiation in esophageal and EGJ adenocarcinomas by immunohistochemistry for
      chromogranin A and synaptophysin and evaluated the clinical significance of NE
      differentiation in 83 patients (10 patients who had a complete tumor response and
      73 patients who had residual tumor in resection specimens) who received
      preoperative chemoradiation. RESULTS: Of 73 patients who had residual tumor after
      preoperative treatment, 52% showed NE differentiation. The proportion of tumor
      cells with NE differentiation had increased from 6% +/- 18% in pretreatment
      biopsy specimens to 47% +/- 42% (P = .00003) in posttreatment resection specimens
      in 30 patients who had paired pretreatment biopsy and resection specimens
      available. Disease-free survival (P = .002) and overall survival (P = .006) were
      significantly better in patients who had a complete tumor response than in
      patients who had residual tumor. Among patients who had residual tumor after
      preoperative chemoradiation, disease-free survival (P = .03) and overall survival
      (P = .045) were significantly better in patients who had residual tumor without
      NE differentiation than in patients who had residual tumor with NE
      differentiation. In multivariate analysis, the presence of NE differentiation in
      residual tumor was a prognostic factor for worse disease-free survival (P = .02)
      independent of pathologic stage and extent of residual tumor. CONCLUSIONS: The
      results from this study suggested that tumor cells with NE differentiation were
      more resistant to neoadjuvant chemoradiation in patients with esophageal and EGJ
      adenocarcinomas. The presence of NE differentiation in residual tumor was
      associated with poor survival after preoperative neoadjuvant therapy.

PMID- 16955508
TI  - Treatment of metastatic sarcoma to the liver with bland embolization.
AB  - BACKGROUND: The authors evaluated the impact of bland particle embolization on
      survival in patients with metastatic sarcoma to the liver. METHODS: Twenty-four
      patients with liver-dominant metastases from sarcoma were treated with particle
      embolization from 1996 to 2002. Primary tumors included 16 gastrointestinal
      stromal tumors (GISTs), 7 intestinal leiomyosarcomas, and 1 liposarcoma. Thirteen
      patients had known extrahepatic disease. Embolization was performed by using
      polyvinyl alcohol or trisacryl microspheres to effect stasis in the target
      vessel(s). Follow-up images to assess response were obtained 4 weeks after the
      procedure. Decrease in the size of the target lesion by >25% or development of
      >50% necrosis on follow-up imaging was considered a treatment response. RESULTS:
      Nineteen patients had metachronous liver metastases, and the median disease-free
      interval was 22 months (range 10-156 months) from resection of the primary tumor.
      Ten patients underwent prior liver resection for metastatic disease. Of 15
      evaluable patients, 9 patients (60%) had a radiographic response. The median
      follow-up for all patients was 21 months. The median follow-up for surviving
      patients was 59 months. Overall survival from the time of initial embolization
      was 62% at 1 year, 41% at 2 years, and 29% at 3 years. Patients who had
      radiographic evidence of response survived significantly longer than patients who
      did not respond (63 months vs. 19 months; P < .007). Patients with GIST survived
      significantly longer than patients with visceral leiomyosarcoma (median, 36
      months vs. 18 months; P < .03). CONCLUSIONS: Bland embolization was efficacious
      in some patients with metastatic sarcoma to the liver. Radiographic evidence of
      response was correlated with improved survival. This regional therapy may enter
      the treatment algorithm for patients who have unresectable disease or disease
      that has failed conventional therapies.

PMID- 16955511
TI  - Lipid tubes with a temperature-tunable diameter.

PMID- 16955510
TI  - Activity of 9-nitro-camptothecin, an oral topoisomerase I inhibitor, in
      myelodysplastic syndrome and chronic myelomonocytic leukemia.
AB  - BACKGROUND: Topoisomerase I inhibitors, like topotecan, have activity in
      myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). 9
      Nitro-camptothecin (9-NC) is a new oral topoisomerase inhibitor with a good
      safety profile. The aims of the current study were to evaluate the activity and
      safety of 9-NC in MDS and CMML. METHODS: Adults with a diagnosis of MDS (n = 12)
      and CMML (n = 32) received 9-NC 2 mg/m(2) orally daily 5 days a week, every 4 to
      6 weeks. RESULTS: Overall, 5 (11%) patients achieved complete response (CR), 7
      (16%) had a partial response (PR), and 6 (14%) had hematologic improvement (HI),
      for an overall response rate of 41%. The response rate was similar in MDS and
      CMML. Severe (Grade 3-4) side effects included nausea and vomiting (7%), diarrhea
      (18%), other gastrointestinal toxicities (5%), and genitourinary toxicities
      (12%). CONCLUSIONS: 9-NC is active in MDS and CMML. The paucity of available
      therapies in CMML makes 9-NC a good candidate for further studies as a single
      agent, or in combination with decitabine, 5-azacitidine or cytarabine.

PMID- 16955512
TI  - Properties of hydration shells of protein molecules at their pressure- and
      temperature-induced native-denatured transition.
AB  - Properties of water at the surface of biomolecules are important for their
      conformational stability. The behaviour of hydrating water at protein transition
      (t) pressures P(t) and temperatures T(t) , with the points (P(t),T(t) ) lying in
      the Native-Denatured (N-D) transition line, is studied. Hydration shells at the
      hydrophilic regions of protein molecules with surface charge density sigma are
      investigated with the help of the equation of state of water in an open system.
      The local values of sigma rather close to each other (sigma(D) approximately 0.3
      C m(-2)) are found for six different experimental lines of the N-D transition
      found in the literature. The values sigma(D) correspond to the crossings of the
      total pressure (P(t)+Pi) vs sigma isotherms at different T(t) (Pi
      electrostriction pressure). The pressures P(t) and temperatures T(t) appear to be
      related with some selected sites at the surfaces of the protein molecules.

PMID- 16955513
TI  - Identification of alkaline proteins that are differentially expressed in an
      overgrowth-mediated growth arrest and cell death of Escherichia coli by proteomic
      methodologies.
AB  - The available Escherichia coli genome sequences offer an opportunity to further
      expand our understanding of this bacterium. In the current study, we present a
      rapid method for the isolation of bacterial alkaline proteins using acid
      incubation, purification and protein array by 2-DE, followed by protein
      identification using MS. Fifty-seven proteins were randomly chosen, in which 55
      were identified by a database searching of MS data. The searching results showed
      that most of these alkaline proteins were involved in special functions within
      the cell, suggesting that alkaline proteome is an ideal fraction for an
      understanding of their special functions. Furthermore, alkaline proteomes were
      compared between the period of majority live bacteria (18-h culture), the period
      of similar amount of live and dead bacteria (30-h culture) and the period of
      majority dead bacteria (48-h culture). Six proteins were identified as
      differentially expressed targets, in which putative transcriptional regulator and
      superoxide dismutase genes were cloned and expressed for antiserum preparations.
      The antisera were applied for the confirmation of results obtained from 2-DE. The
      presented data clearly reveal that alkaline proteome analysis by 2-DE with MS
      plays an important role in the understanding of protein functions within the
      cell, and six alkaline proteins are determined as key ones in an overgrowth
      mediated growth cycle of E. coli.

PMID- 16955514
TI  - Origin of magnetosome membrane: proteomic analysis of magnetosome membrane and
      comparison with cytoplasmic membrane.
AB  - Prokaryotes are known to have evolved one or more unique organelles. Although
      several hypotheses have been proposed concerning the biogenesis of these
      intracellular components, the majority of these proposals remains unclear.
      Magnetotactic bacteria synthesize intracellular magnetosomes that are enclosed by
      lipid bilayer membranes. From the identification and characterization of several
      surface and transmembrane magnetosome proteins, we have postulated that
      magnetosomes are derived from the cytoplasmic membrane (CM). To confirm this
      hypothesis, a comparative proteomic analysis of the magnetosome membrane (MM) and
      CM of the magnetotactic bacterium, Magnetospirillum magneticum AMB-1, was
      undertaken. Based on the whole genome sequence of M. magneticum AMB-1, 78
      identified MM proteins were also found to be prevalent in the CM, several of
      which are related to magnetosome biosynthesis, such as Mms13, which is tightly
      bound on the magnetite surface. Fatty acid analysis was also conducted, and
      showed a striking similarity between the CM and MM profiles. These results
      suggest that the MM is derived from the CM.

PMID- 16955515
TI  - Cleaning of raw peptide MS/MS spectra: improved protein identification following
      deconvolution of multiply charged peaks, isotope clusters, and removal of
      background noise.
AB  - The dominant ions in MS/MS spectra of peptides, which have been fragmented by low
      energy CID, are often b-, y-ions and their derivatives resulting from the
      cleavage of the peptide bonds. However, MS/MS spectra typically contain many more
      peaks. These can result not only from isotope variants and multiply charged
      replicates of the peptide fragmentation products but also from unknown
      fragmentation pathways, sample-specific or systematic chemical contaminations or
      from noise generated by the electronic detection system. The presence of this
      background complicates spectrum interpretation. Besides dramatically prolonged
      computation time, it can lead to incorrect protein identification, especially in
      the case of de novo sequencing algorithms. Here, we present an algorithm for
      detection and transformation of multiply charged peaks into singly charged
      monoisotopic peaks, removal of heavy isotope replicates, and random noise. A
      quantitative criterion for the recognition of some noninterpretable spectra has
      been derived as a byproduct. The approach is based on numerical spectral analysis
      and signal detection methods. The algorithm has been implemented in a stand-alone
      computer program called MS Cleaner that can be obtained from the authors upon
      request.

PMID- 16955516
TI  - GNBSL: a new integrative system to predict the subcellular location for Gram
      negative bacteria proteins.
AB  - This paper proposes a new integrative system (GNBSL--Gram-negative bacteria
      subcellular localization) for subcellular localization specifized on the Gram
      negative bacteria proteins. First, the system generates a position-specific
      frequency matrix (PSFM) and a position-specific scoring matrix (PSSM) for each
      protein sequence by searching the Swiss-Prot database. Then different features
      are extracted by four modules from the PSFM and the PSSM. The features include
      whole-sequence amino acid composition, N- and C-terminus amino acid composition,
      dipeptide composition, and segment composition. Four probabilistic neural network
      (PNN) classifiers are used to classify these modules. To further improve the
      performance, two modules trained by support vector machine (SVM) are added in
      this system. One module extracts the residue-couple distribution from the amino
      acid sequence and the other module applies a pairwise profile alignment kernel to
      measure the local similarity between every two sequences. Finally, an additional
      SVM is used to fuse the outputs from the six modules. Test on a benchmark dataset
      shows that the overall success rate of GNBSL is higher than those of PSORT-B,
      CELLO, and PSLpred. A web server GNBSL can be visited from
      http://166.111.24.5/webtools/GNBSL/index.htm.

PMID- 16955517
TI  - Proteomic analysis of cold adaptation in a Siberian permafrost bacterium-
      Exiguobacterium sibiricum 255-15 by two-dimensional liquid separation coupled
      with mass spectrometry.
AB  - Bacterial cold adaptation in Exiguobacterium sibiricum 255-15 was studied on a
      proteomic scale using a 2-D liquid phase separation coupled with MS technology.
      Whole-cell lysates of E. sibiricum 255-15 grown at 4 degrees C and 25 degrees C
      were first fractionated according to pI by chromatofocusing (CF), and further
      separated based on hydrophobicity by nonporous silica RP HPLC (NPS-RP-HPLC) which
      was on-line coupled with an ESI-TOF MS for intact protein M(r) measurement and
      quantitative interlysate comparison. Mass maps were created to visualize the
      differences in protein expression between different growth temperatures. The
      differentially expressed proteins were then identified by PMF using a MALDI-TOF
      MS and peptide sequencing by MS/MS with a MALDI quadrupole IT TOF mass
      spectrometer (MALDI-QIT-TOF MS). A total of over 500 proteins were detected in
      this study, of which 256 were identified. Among these proteins 39 were cold
      acclimation proteins (Caps) that were preferentially or uniquely expressed at 4
      degrees C and three were homologous cold shock proteins (Csps). The homologous
      Csps were found to be similarly expressed at 4 degrees C and 25 degrees C, where
      these three homologous Csps represent about 10% of the total soluble proteins at
      both 4 degrees C and 25 degrees C.

PMID- 16955518
TI  - Interplay between O2 and SnO2: oxygen ionosorption and spectroscopic evidence for
      adsorbed oxygen.
AB  - Tin dioxide is the most commonly used material in commercial gas sensors based on
      semiconducting metal oxides. Despite intensive efforts, the mechanism responsible
      for gas-sensing effects on SnO(2) is not fully understood. The key step is the
      understanding of the electronic response of SnO(2) in the presence of background
      oxygen. For a long time, oxygen interaction with SnO(2) has been treated within
      the framework of the "ionosorption theory". The adsorbed oxygen species have been
      regarded as free oxygen ions electrostatically stabilized on the surface (with no
      local chemical bond formation). A contradiction, however, arises when connecting
      this scenario to spectroscopic findings. Despite trying for a long time, there
      has not been any convincing spectroscopic evidence for "ionosorbed" oxygen
      species. Neither superoxide ions O(2)(-), nor charged atomic oxygen O,(-) nor
      peroxide ions O(2)(2-) have been observed on SnO(2) under the real working
      conditions of sensors. Moreover, several findings show that the superoxide ion
      does not undergo transformations into charged atomic oxygen at the surface, and
      represents a dead-end form of low-temperature oxygen adsorption on reduced metal
      oxide.

PMID- 16955519
TI  - On the influence of the local environment on the CO stretching frequencies in
      native myoglobin: assignment of the B-states in MbCO.

PMID- 16955520
TI  - Nitric oxide and peroxynitrite have different antiviral effects against
      hantavirus replication and free mature virions.
AB  - Reactive nitrogen intermediates (RNI), like nitric oxide (NO) and peroxynitrite,
      have antiviral effects against certain viruses. Hantaviruses, like other members
      of the Bunyaviridae family, have previously not been shown to be sensitive to
      RNI. In this study, we compared the effects of NO and peroxynitrite on hantavirus
      replication and free mature virions in vitro, and of inducible nitric oxide
      synthase (iNOS) in hantavirus-infected suckling mice. The NO-generating compound
      S-nitroso-N-acetylpenicillamine (SNAP), as well as cytokine-induced NO, strongly
      inhibited hantavirus replication in Vero E6 cells, while pretreatment of free
      virions with SNAP only had a limited effect on their viability. In contrast, 3
      morpholinosydnonimine hydrochloride (SIN-1), a peroxynitrite donor, inhibited
      virus replication only to a very low extent in vitro, but pretreatment of virus
      with SIN-1 led to a considerably lowered viability of the virions. Infections of
      various human cell types per se did not induce NO production. The viral titers in
      iNOS(-/-) mice were higher compared to the controls, suggesting that NO inhibits
      hantavirus replication in vivo. In conclusion, we show that NO has strong
      antiviral effects on hantavirus replication, and peryoxynitrite on mature free
      virions, suggesting that different RNI can have different effects on various
      parts of the replication cycle for the same virus.

PMID- 16955521
TI  - T and B lymphocytes exert distinct effects on the homeostasis of NK cells.
AB  - There is growing evidence that lymphocytes impact the development and/or function
      of other lymphocyte populations. Based on such observations we have tested
      whether the NK cell compartment was phenotypically and functionally altered in
      the absence of B and/or T cells. Here we show that T cell deficiency
      significantly accelerates BM NK cell production and the subsequent seeding of
      splenic and liver NK cell compartments. In contrast, B cell deficiency reduces
      splenic NK cell survival. In the absence of T and B cells, the size of the NK
      cell compartments is determined by the combination of these positive and negative
      effects. Even though NK cell homeostasis is significantly altered, NK cells from
      T and/or B cell-deficient mice show a normal capacity to kill a susceptible
      target cell line and to produce IFN. Nevertheless, we noted that the usage of MHC
      class I-specific Ly49 family receptors was significantly altered in the absence
      of T and/or B cells. In general, B cell deficiency expanded Ly49 receptor usage,
      while T cell deficiency exerted both positive and negative effects. These
      findings show that B and T cells significantly and differentially influence the
      homeostasis and the phenotype of NK cells.

PMID- 16955522
TI  - Phagocytosis of Leishmania donovani amastigotes is Rac1 dependent and occurs in
      the absence of NADPH oxidase activation.
AB  - Macrophages produce little superoxide during phagocytosis of Leishmania donovani
      amastigotes. In this study, we characterized molecular events associated with L.
      donovani amastigotes uptake by mouse macrophages, to further define the
      mechanisms by which they are internalized without triggering superoxide
      production. Using transient transfections, we first showed that internalization
      of L. donovani amastigotes is mediated by the GTPases Rac1 and Arf6, of which
      Rac1 is recruited and retained on parasite-containing phagosomes. Next, we showed
      that, whereas internalization of amastigotes induced no superoxide release, co
      internalization of serum-opsonized zymozan and amastigotes resulted in superoxide
      production. Furthermore, in co-internalization experiments, we detected
      superoxide production in over 95% of phagosomes containing IgG-opsonized SRBC
      compared to 5% of amastigote-harboring phagosomes. These results suggest that
      amastigotes evade the ability of macrophages to produce superoxide during
      phagocytosis. Consistently, we observed that amastigotes induced barely
      detectable phosphorylation of the NADPH oxidase component p47phox, leading to a
      defective phagosomal recruitment of p67phox and p47phox. Finally, we showed that
      amastigotes disrupt phagosomal lipid raft integrity, potentially interfering with
      NADPH oxidase assembly. Collectively, our results indicate that internalization
      of L. donovani amastigotes is a Rac1- and Arf6-dependent process that occurs in
      the absence of significant NADPH oxidase activation.

PMID- 16955523
TI  - Precursor frequency can compensate for lower TCR expression in T cell competition
      during priming in vivo.
AB  - The factors controlling clonal dominance of cytotoxic T lymphocyte (CTL)
      responses are currently not well understood. To study the functional impact of
      the strength of the interaction of a T cell with an antigen-presenting cell in
      this context, we established a new mouse model comprised of two T cell receptor
      (TCR)-transgenic strains expressing the identical TCR in differing amounts, hence
      providing two CTL clones with different avidities but identical specificity and
      affinity. Utilizing this new model, we show that upon antigen challenge higher
      avidity CTL expand at the expense of moderate-avidity CTL in vivo if present in
      equal numbers. Beyond this, moderate-avidity T cells can also contribute to a CTL
      response when present in excess. These results suggest that in addition to a
      proposed affinity/avidity threshold, the precursor frequency is important in
      defining clonal dominance. A new model in which TCR density and precursor
      frequency define the outcome of a CTL response is discussed.

PMID- 16955524
TI  - Total synthesis of cyclic diterpene tonantzitlolone based on a highly
      stereoselective substrate-controlled aldol reaction and ring-closing metathesis.
AB  - The total synthesis of the cyclic diterpene ent-tonantzitlolone (ent-1) is
      presented. Key steps for assembling the macrocyclic core structure of 1 are a
      highly selective aldol reaction and an E selective ring-closing metathesis
      reaction. A detailed investigation of these two steps and the final
      transformations towards the completion of the synthesis is disclosed.

PMID- 16955525
TI  - Synthesis of novel rod-shaped and star-shaped fluorescent phosphane oxides-
      nonlinear optical properties and photophysical properties.
AB  - The design of a new class of fluorophores is presented. Some push-pull
      chromophores (D-pi-A) containing polyphenylethynyl units and a phosphane oxide
      moiety were efficiently prepared from common intermediates. Straightforward
      syntheses gave novel one-armed, rod-shaped and three-armed, star-shaped
      fluorophores. The optical properties of the resulting star-shaped derivatives
      were evaluated, showed high fluorescence quantum yields, and their excitation
      induces very efficient charge redistribution. Moreover, thanks to their push-pull
      character, the molecules exhibited significant second-order NLO properties with
      good transparency, up to 67x10(-30) esu at 1907 nm, with an absorption lambdamax
      at 369 nm. The effect of the donor group and of the number of phenylethynyl arms
      have been studied in this work.

PMID- 16955527
TI  - Structural identification of conjugated molecules on metal surfaces by means of
      soft vibrations.

PMID- 16955526
TI  - Monodentate phosphines provide highly active catalysts for Pd-catalyzed C-N bond
      forming reactions of heteroaromatic halides/amines and (H)N-heterocycles.

PMID- 16955528
TI  - Asymmetry induction by cooperative intermolecular hydrogen bonds in surface
      anchored layers of achiral molecules.
AB  - The mesoscale induction of two-dimensional supramolecular chirality (formation of
      2D organic domains with a single handedness) was achieved by self-assembly of
      1,2,4-benzenetricarboxylic (trimellitic) acid on a Cu(100) surface at elevated
      temperatures. The combination of spectroscopic [X-ray photoelectron spectroscopy
      (XPS) and near-edge X-ray absorption fine structure (NEXAFS)], real-space-probe
      [scanning tunneling microscopy (STM)], and computational [density functional
      theory (DFT)] methods allows a comprehensive characterization of the obtained
      organic adlayers, where details of molecular adsorption geometry, intermolecular
      coupling, and surface chemical bonding are elucidated. The trimellitic acid
      species, comprising three functional carboxylic groups, form distinct stable
      mirror-symmetric hydrogen-bonded domains. The chiral ordering is associated with
      conformational restriction in the domains: molecules anchor to the substrate with
      an ortho carboxylate group, providing two para carboxylic acid moieties for
      collective lateral interweaving through H bonding, which induces a specific tilt
      of the molecular plane. The ease of molecular symmetry switching in domain
      formation makes homochiral-signature propagation solely limited by the terrace
      width. The molecular layer modifies the morphology of the underlying copper
      substrate and induces mum-sized strictly homochiral terraces.

PMID- 16955529
TI  - A proteomic approach for the characterization of C677T mutation of the human gene
      methylenetetrahydrofolate reductase.
AB  - Methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of
      methylenetetrahydrofolate (CH2H4folate) to methyltetrahydrofolate (CH3H4folate).
      The C677T mutation is a common polymorphism of the human enzyme that leads to the
      replacement of Ala222Val, thermolability of MTHFR, and mild elevation of plasma
      homocysteine levels. A mild hyperhomocysteinemia is known to be risk factor for
      cardiovascular and thrombotic diseases, ischemic stroke, neural tube defects,
      late on-set dementia, and pregnancy complications. Human plasma of subjects
      carrying the C677T mutation in the MTHFR gene has been investigated for their
      protein pattern in order to identify novel molecular hallmarks. 2-D analysis of
      the plasma protein allowed the identification of a specific pattern associated
      with the TT mutant genotype. Noteworthy, we found one spot shifted to a more
      basic pI in mutant individuals, and MS identification corresponded to vitamin D
      binding protein (DBP or group component (Gc) globulin). MS/MS peptide sequencing
      allowed to discriminate different allelic variants in the investigated clinical
      groups. These data confirmed by molecular genetic analysis highlight the novel
      association between the C677T MTHFR genotype with the Gc2 polymorphism of the
      DBP. Moreover, we found a quantitative reduction of Apolipoprotein A-I in mutant
      individuals, which was associated, in previous studies by others to an increased
      cardiovascular risk.

PMID- 16955530
TI  - Peak quantification in surface-enhanced laser desorption/ionization by using
      mixture models.
AB  - Surface-enhanced laser desorption/ionization (SELDI) time of flight (TOF) is a
      mass spectrometry technology for measuring the composition of a sampled protein
      mixture. A mass spectrum contains peaks corresponding to proteins in the sample.
      The peak areas are proportional to the measured concentrations of the
      corresponding proteins. Quantifying peak areas is difficult for existing methods
      because peak shapes are not constant across a spectrum and because peaks often
      overlap. We present a new method for quantifying peak areas. Our method
      decomposes a spectrum into peaks and a baseline using so-called statistical
      finite mixture models. We illustrate our method in detail on 8 samples from
      culture media of adipose tissue and globally on 64 samples from serum to compare
      our method to the standard Ciphergen method. Both methods give similar estimates
      for singleton peaks, but not for overlapping peaks. The Ciphergen method
      overestimates the heights of such peaks while our method still gives appropriate
      estimates. Peak quantification is an important step in pre-processing SELDI-TOF
      data and improvements therein will pay off in the later biomarker discovery
      phase.

PMID- 16955531
TI  - Towards the development of mixed MT(1)-agonist/MT(2)-antagonist melatonin
      receptor ligands.
AB  - Herein we report attempts to optimize the pharmacological properties of 5-(2
      hydroxyethoxy)-N-acetyltryptamine (5-HEAT), a melatonin receptor ligand
      previously described by us. Several 5-substituted and 2,5-disubstituted N
      acyltryptamines were synthesized and evaluated in vitro for the human cloned
      MT(1) and MT(2) receptors. From this series of N-acyltryptamines the 2-bromo
      derivative (5 c) retains the interesting efficacy profile of 5-HEAT and shows
      increased melatonin receptor affinities; it represents one of the first examples
      of a high-affinity MT(1) agonist/MT(2) antagonist. Some other full agonists for
      both melatonin receptors which exhibit similar or increased affinity relative to
      that of melatonin were obtained.

PMID- 16955532
TI  - Everolimus drug interactions: application of a classification system for clinical
      decision making.
AB  - INTRODUCTION: More than half of all drugs used in medical practice are
      metabolized by cytochrome CYP3A. Coadministration of drugs that share this
      elimination pathway may lead to pharmacokinetic drug interactions. Efforts are
      underway by clinical, drug development and regulatory scientists to classify
      CYP3A-related drug interactions with the ultimate goal of improving guidance for
      clinical intervention. The CYP3A inhibitory classification system ranks
      inhibitors according to the fold-increase in area-under-the-curve (AUC) of a
      probe substrate as: strong (> or =5-fold), moderate (>2.0- to 4.9-fold), or weak
      (< or =2.0-fold). This classification system was applied to characterize
      everolimus as a CYP3A substrate.Methods. Five open-label crossover drug
      interaction studies were performed in 12-16 healthy subjects each. Subjects
      received a single 2 mg dose of everolimus alone and again during single- or
      multiple-dose treatment with the probe inhibitors ketoconazole, erythromycin,
      verapamil, cyclosporine and atorvastatin.Results. The fold-increase in everolimus
      AUC was: 15.0 with the strong inhibitor ketoconazole; 4.4, 3.5 and 2.7 with the
      moderate inhibitors erythromycin, verapamil and cyclosporine; and no change with
      the weak inhibitor atorvastatin. Subjects with low baseline AUCs when everolimus
      was given alone tended to have AUC increases of a higher magnitude (more potent
      interaction) in the presence of an inhibitor.Conclusions. Strong CYP3A inhibitors
      should be avoided when possible during everolimus treatment as compensatory
      everolimus dose reductions could be difficult to manage. Everolimus therapeutic
      drug monitoring should be used to guide individualized dose adjustments when
      moderate CYP3A inhibitors are added to or withdrawn from the regimen. Routine
      everolimus therapeutic drug monitoring should be sufficient to determine whether
      dose adjustments are needed when weak CYP3A inhibitors are coadministered. This
      rational and systematic approach to drug interactions on everolimus yielded
      clinically useful, structured guidelines for dose adjustment.

PMID- 16955533
TI  - Stability analysis for drugs with multiple active ingredients.
AB  - For every drug product on the market, the United States Food and Drug
      Administration (FDA) requires that an expiration dating period (shelf-life) must
      be indicated on the immediate container label. For determination of the
      expiration dating period of a drug product, regulatory requirements and
      statistical methodology are provided in the FDA and ICH Guidelines. However, this
      guideline is developed for drug products with a single active ingredient. There
      are many drug products consisting of multiple active ingredients, especially for
      most traditional Chinese medicine. In this article, we propose a statistical
      method for determining the shelf-life of a drug product with multiple active
      ingredients following similar idea as suggested by the FDA and assuming that
      these active ingredients are linear combinations of some factors. Stability data
      observed from a traditional Chinese medicine were analysed to illustrate the
      proposed method.

PMID- 16955534
TI  - Enhanced therapeutic efficacy of oncolytic herpes vector G207 against human non
      small cell lung cancer--expression of an RNA-binding protein, Musashi1, as a
      marker for the tailored gene therapy.
AB  - BACKGROUND: Oncolytic herpes vectors like G207 have shown considerable promise in
      the treatment of solid tumors, but their potency must be enhanced for the full
      achievement of therapeutic efficacy. Deletion of the innate gamma34.5 gene made
      these vectors extremely safe, but their efficacy was also severely attenuated.
      Use of tumor-specific promoters is one method to direct toxicity and enhance
      efficacy against tumors. Recently, Musashi1 has been shown expressed in some
      tumor tissues. METHODS: Eleven human cancer cell lines including five non-small
      cell lung cancers (NSCLCs) were investigated. Musashi1 mRNA expression was
      examined by RT-PCR analysis. Western blotting was also performed. Transcriptional
      activity of P/musashi1 in NSCLCs was assayed by GFP reporter plasmids. Then we
      constructed a defective amplicon vector containing musashi1 promoter/ICP34.5 with
      G207 as helper virus (dvM345). In vitro cytotoxicity against NSCLCs and growth
      characteristics of helper virus were examined. A Lu-99 subcutaneous tumor model
      was used in an animal study. The tumor volume treated with G207 alone or dvM345
      was measured. RESULTS: Musashi1 mRNA was detected in four cell lines. Two in five
      NSCLCs were positive, and P/musashi1 was proved functional within them. Against
      these cell lines, dvM345 showed enhanced cytotoxicity, and helper viral growth
      was augmented. A subcutaneous tumor study confirmed the enhanced therapeutic
      efficacy of G207 by dvM345 without compromising safety. CONCLUSIONS: These
      results suggest that Musashi1 might be involved in the development of several
      carcinomas including NSCLC. In the context of oncolytic herpes vector strategy,
      the P/musashi1-ICP34.5 method could be used for the treatment of cancers
      expressing Musashi1.

PMID- 16955535
TI  - Cross-over trials in Statistics in Medicine: the first '25' years.
AB  - Papers on cross-over trials that have appeared in the first 25 years of
      Statistics in Medicine are reviewed. Papers on bioequivalence are also
      considered. After a brief statistical summary, individual papers are discussed
      under seven headings: 1. The two-stage analysis of AB/BA trials, 2. Baselines, 3.
      Binary and categorical data, 4. Survival data, 5. Modelling carry-over, 6.
      Bioequivalence and 7. Components of variation. Finally, a brief assessment of the
      importance in this field of Statistics in Medicine is given.

PMID- 16955536
TI  - Nitrogen isotopic composition in hair protein is different in liver cirrhotic
      patients.
AB  - The stable-isotopic composition of nitrogen (delta15N) or carbon (delta13C) of
      body tissues depends on the isotopic composition of food sources and on shifts
      due to isotopic fractionation during metabolism. As little is known about the
      effects of pathophysiological conditions we measured delta15N and delta13C values
      in hair and hair amino acids of patients with cirrhosis (n = 21) and compared the
      results with those of healthy subjects (n = 100) randomly selected from the 1987
      1988 VERA German nutrition survey population. Cirrhosis was reflected in lower
      hair 15N abundances (6.7 vs. 9.9 per thousand delta15N; P < 0.001) whereas hair
      13C abundances did not differ from healthy subjects (-19.4 vs. -19.6 per thousand
      13C). Distinct patterns of delta15N and delta13C values were measured in hair
      amino acids. The delta15N values of phenylalanine were significantly higher in
      cirrhotics (P < 0.001). With the exception of isoleucine, threonine, and proline
      all other measured amino acids showed lower delta15N values than healthy subjects
      (P < 0.001). Lower hair delta15N values were associated with cirrhotic liver
      disease which suggests that under this condition the altered liver amino acid
      metabolism affects the nitrogen isotopic composition of the amino acids used for
      hair protein synthesis. It remains to be determined in controlled studies whether
      the altered nitrogen isotopic composition directly reflects the
      pathophysiological condition or is related to differences in dietary protein
      intake from plant or animal food sources.

PMID- 16955537
TI  - Statistical distribution of the difference of two proportions.
AB  - Differences of two proportions or rates occur most frequently in biomedical
      research. However, as far as published work in the Statistics in Medicine are
      concerned, only approximations have been used to study the distribution of such
      differences. In this Letter, we derive the exact probability distribution of the
      difference of two proportions. The expression involves a well-known special
      function. It is expected that this result could be widely useful for medical
      practitioners.

PMID- 16955538
TI  - Choice of time scale and its effect on significance of predictors in longitudinal
      studies.
AB  - Time-to-event regression is a frequent tool in biomedical research. In clinical
      trials this time is usually measured from the beginning of the study. The same
      approach is often adopted in the analysis of longitudinal observational studies.
      However, in recent years there has appeared literature making a case for the use
      of the date of birth as a starting point, and thus utilize age as the time-to
      event. In this paper, we explore different types of age-scale models and compare
      them with time-on-study models in terms of the estimated regression coefficients
      they produce. We consider six proportional hazards regression models that differ
      in the choice of time scale and in the method of adjusting for the years before
      the study. By considering the estimating equations of these models as well as
      numerical simulations we conclude that correct adjustment for the age at entry is
      crucial in reducing bias of the estimated coefficients. The unadjusted age-scale
      model is inferior to any of the five other models considered, regardless of their
      choice of time scale. Additionally, if adjustment for age at entry is made, our
      analyses show very little to suggest that there exists any practically meaningful
      difference in the estimated regression coefficients depending on the choice of
      time scale. These findings are supported by four practical examples from the
      Framingham Heart Study.

PMID- 16955539
TI  - A comparison of heterogeneity variance estimators in combining results of
      studies.
AB  - For random effects meta-analysis, seven different estimators of the heterogeneity
      variance are compared and assessed using a simulation study. The seven estimators
      are the variance component type estimator (VC), the method of moments estimator
      (MM), the maximum likelihood estimator (ML), the restricted maximum likelihood
      estimator (REML), the empirical Bayes estimator (EB), the model error variance
      type estimator (MV), and a variation of the MV estimator (MVvc). The performance
      of the estimators is compared in terms of both bias and mean squared error, using
      Monte Carlo simulation. The results show that the REML and especially the ML and
      MM estimators are not accurate, having large biases unless the true heterogeneity
      variance is small. The VC estimator tends to overestimate the heterogeneity
      variance in general, but is quite accurate when the number of studies is large.
      The MV estimator is not a good estimator when the heterogeneity variance is small
      to moderate, but it is reasonably accurate when the heterogeneity variance is
      large. The MVvc estimator is an improved estimator compared to the MV estimator,
      especially for small to moderate values of the heterogeneity variance. The two
      estimators MVvc and EB are found to be the most accurate in general, particularly
      when the heterogeneity variance is moderate to large.

PMID- 16955540
TI  - Bayesian synthesis of epidemiological evidence with different combinations of
      exposure groups: application to a gene-gene-environment interaction.
AB  - Meta-analysis to investigate the joint effect of multiple factors in the
      aetiology of a disease is of increasing importance in epidemiology. This task is
      often challenging in practice, because studies typically concentrate on studying
      the effect of only one exposure, sometimes may report the interaction between two
      exposures, but rarely address more complex interactions that involve more than
      two exposures. In this paper, we develop a meta-analysis framework that combines
      estimates from studies of multiple exposures. A key development is an approach to
      combining results from studies that report information on any subset or
      combination of the full set of exposures. The model requires assumptions to be
      made about the prevalence of the specific exposures. We discuss several possible
      model specifications and prior distributions, including information internal and
      external to the meta-analysis data set, and using fixed-effect and random-effects
      meta-analysis assumptions. The methodology is implemented in an original meta
      analysis of studies relating the risk of bladder cancer to two N
      acetyltransferase genes, NAT1 and NAT2, and smoking status.

PMID- 16955542
TI  - Isolation of targeted AAV2 vectors from novel virus display libraries.
AB  - Random peptide ligands displayed on viral capsids are emerging tools for
      selection of targeted gene transfer vectors even without prior knowledge of the
      potential target cell receptor. We have previously introduced adeno-associated
      viral (AAV)-displayed peptide libraries that ensure encoding of displayed
      peptides by the packaged AAV genome. A major limitation of these libraries is
      their contamination with wild-type (wt) AAV. Here we describe a novel and
      improved library production system that reliably avoids generation of wt AAV by
      use of a synthetic cap gene. Selection of targeted AAV vectors from wt-containing
      and the novel wt-free libraries on cell types with different permissivity for wt
      AAV2 replication suggested the superiority of the wt-free library. However, from
      both libraries highly specific peptide sequence motifs were selected which
      improved transduction of cells with moderate or low permissivity for AAV2
      replication. Strong reduction of HeLa cell transduction compared to wt AAV2 and
      only low level transduction of non-target cells by some selected clones showed
      that not only the efficiency but also the specificity of gene transfer was
      improved. In conclusion, our study validates and improves the unique potential of
      virus display libraries for the development of targeted gene transfer vectors.

PMID- 16955543
TI  - A comparative investigation of methods for logistic regression with separated or
      nearly separated data.
AB  - In logistic regression analysis of small or sparse data sets, results obtained by
      classical maximum likelihood methods cannot be generally trusted. In such
      analyses it may even happen that the likelihood meets the convergence criteria
      while at least one parameter estimate diverges to +/-infinity. This situation has
      been termed 'separation', and it typically occurs whenever no events are observed
      in one of the two groups defined by a dichotomous covariate. More generally,
      separation is caused by a linear combination of continuous or dichotomous
      covariates that perfectly separates events from non-events. Separation implies
      infinite or zero maximum likelihood estimates of odds ratios, which are usually
      considered unrealistic. I provide some examples of separation and near-separation
      in clinical data sets and discuss some options to analyse such data, including
      exact logistic regression analysis and a penalized likelihood approach. Both
      methods supply finite point estimates in case of separation. Profile penalized
      likelihood confidence intervals for parameters show excellent behaviour in terms
      of coverage probability and provide higher power than exact confidence intervals.
      General advantages of the penalized likelihood approach are discussed.

PMID- 16955545
TI  - American Society for Mass Spectrometry directory 2006.

PMID- 16955544
TI  - Abstracts of the 29th European Peptide Symposium, September 3-8, 2006, Gdansk,
      Poland.

PMID- 16955546
TI  - DNA repair: from molecular mechanism to human disease.

PMID- 16955547
TI  - Disclosure of medical errors involving gametes and embryos.

PMID- 16955548
TI  - Readers' response to "so what is a sham peer review?".

PMID- 16955549
TI  - Readers' response to "so what is a sham peer review?".

PMID- 16955550
TI  - Preventive cardiology in Germany: HeartScore.

PMID- 16955551
TI  - History of medicine: Sir Dominic Corrigan, MD.

PMID- 16955552
TI  - Acanthocytes.

PMID- 16955553
TI  - Osteoblast-like cell attachment to and calcification of novel phosphonate
      containing polymeric substrates.
AB  - In an attempt to interact natural bone and bone cells with biomaterials and to
      begin to develop modular tissue engineering scaffolds, substrates containing
      phosphonate groups were identified to mimic mineral-protein and natural polymer
      protein interactions. In this study, we investigated poly(vinyl phosphonic acid)
      copolymer integration with existing materials as a graft-copolymer surface
      modification. Phosphonate-containing copolymer-modified surfaces were created and
      shown to have varying phosphate content within different polymeric surfaces. As
      the phosphonate content in the monomer feed approached 30% vinyl phosphonic acid,
      increased osteoblast-like cell adhesion (3- to 8-fold increase in adhesion) and
      proliferation (2- to 10-fold increase in proliferation rate) was observed. Since
      surfaces modified with 30% vinyl phosphonic acid in the feed exhibited a maximal
      cell adhesion and proliferation (9.4 x 10(4) cells/cm(2)/day), it was
      hypothesized that this copolymer composition was optimal for protein-polymer
      interactions. Osteoblast-like cells formed confluent layers and were able to
      differentiate on all surfaces that contained vinyl phosphonic acid. Most
      importantly, cells interacting with these surfaces were able to significantly
      mineralize the surface. These results suggest that phosphonate-containing
      polymers can be used to integrate biomaterials with natural bone and could be
      used for tissue engineering applications.

PMID- 16955555
TI  - Retraction notice to "A medium for the presumptive detection of Enterobacter
      sakazakii in infant formula" [Food Microbiology 21 (5) (2004) 527-533].

PMID- 16955554
TI  - Bilateral cerebellopontine angle and multiple supratentorial masses.

PMID- 16955556
TI  - Microcirculation and wound healing: a historical examination of the meeting of
      disciplines in the 1960s and 1970s.

PMID- 16955557
TI  - [Bone marrow angiogenesis in patients with multiple myeloma as a marker of
      biological behaviour].
AB  - Angiogenesis, the creation of new blood vessels from preexisting vascular nets,
      plays a major role in the development, progression and dissemination of solid
      malignant tumors. Research over the last few years has shown a correlation of
      angiogenesis and the biological behaviour of haematologic malignancies. This
      study focused on the relation of vasoformation, stage of differentiation of
      tumour plasmocytes and type of bone marrow infiltration in patients with multiple
      myeloma (MM) prior to treatment. We evaluated trephine biopsy samples from 55
      patients for microvessel density in 1 mm2 field by monoclonal antibody anti CD34.
      Angiogenesis correlated with the type of infiltration and with stage of
      morphological differentiation. It was highest in the nodular type of infiltration
      with a low level of differentiation, and lowest in grade 1 differentiation with
      an interstitial type of infiltration.

PMID- 16955558
TI  - [The use of immunohistochemistry in the differential diagnosis of thyroid gland
      tumors with follicular growth pattern].
AB  - The aim of the study was to evaluate the expression of galectin-3 (gal3),
      cytokeratin 19 (CK19), neural cell adhesion molecule (NCAM), and E-cadherin
      (Ecad) in thyroid gland tumors with follicular growth pattern with particular
      focus on their use in differential diagnosis. A series of 139 cases - 87
      follicular adenomas (FAs), 26 follicular carcinomas (FCs), and 26 cases of the
      follicular variant of papillary carcinoma (FVPC) was studied. Expression of gal3
      was found in 29/87 (33%) of FAs, in 13/26 (50%) of FCs, and in 24/26 (92%) of
      FVPCs. Expression of CK19 was found in 11/87 (13%) of FAs, in 4/26 (15%) of FCs,
      and in 17/26 (65%) of FVPCs. Expression of NCAM was found in 60/87 (69%) of FAs,
      in 20/26 (77%) of FCs, and in 7/26 (27%) FVPCs. Expression of Ecad was found in
      81/87 (93%) of FAs, in 22/26 (85%) of FCs, and in 17/26 (65%) of FVPCs. The
      sensitivity and specificity of gal3 for malignancy were 0.70 and 0.85, of CK19
      0.48 and 0.98, of NCAM 0.28 and 0.47, and of Ecad 0.48 and 0.20, respectively. A
      significant difference (p < 0.05) in expression of all studied markers between
      FVPC versus FA and FC was found, in contrast to FA and FC. Therefore, the use of
      gal3 and CK19 in differential diagnosis of FVPC versus FA and FC can be
      recommended.

PMID- 16955559
TI  - [Proliferative and apoptotic markers in prostate carcinoma in relation to
      androgen receptor].
AB  - Prostate carcinoma, one of the most frequent male malignancies, is in certain
      stages of its development significantly influenced by androgens. Therefore, we
      carried out a retrospective study on a set of 130 patients with nongeneralized,
      localized prostate carcinoma (stage T1-T2, PSA up to 25 ng/ml). We determined
      immunohistochemically the expression of proliferation markers PCNA and Ki67, Bax,
      p53, Bcl-2, p21waf1, p27kiP1 and compared them with the expression of the
      androgen receptor (AR). Multivariation statistical analysis of the results using
      the chi-square test with Pearson's correction and variability analysis using the
      SPSS 8.0 software program showed a strong correlation of the PCNA and Ki67
      proliferation markers with the expression of hormonal dependence and apoptosis
      markers. The expression of PCNA correlated strongly with p27 kip1 and Bax, while
      the expression of Ki67 correlated most strongly with p27 kip1 and Bcl-2. The
      expression of p27 kip1 correlated with the expression of androgen receptor, PCNA,
      Ki67 as well as Bcl-2. None of the observed markers correlated significantly with
      Gleason's score. We did not find substantial significant relation between the
      observed markers and the expression of p53 and p21 waf1. The results indicate a
      significant role of the expression of p27 kip1 protein in regulating
      proliferative activity and hormonal responsiveness in the initial stage of
      prostate carcinoma.

PMID- 16955560
TI  - [The molecular genetic assessment of prognostic factors in carcioma of the
      prostate: a pilot study].
AB  - The loss of the 8p22 chromosome part and amplification of the 8q24 region (c-myc
      oncogene region) are the most frequent chromosomal aberrations observed in
      prostate carcinoma. We aimed to demonstrate the frequency of these chromosomal
      abnormalities and to assess how they correlate with the prognosis in patients
      with prostate carcinoma. From a set of 130 patients, we selected a group of 17
      who died within five years after the diagnosis had been determined. Due to the
      lack of tumor cells in puncture biopsies, we managed to carry out in situ
      hybridization and assess the result objectively for 9 patients only. In seven
      cases, amplification of the region for c-myc oncogene was found; however, in five
      of them, polyploidy of chromosome 8 was manifested simultaneously. Deletion of
      the 8p22 chromosome part (region for the LPL gene) was found in five cases. A
      normal finding was detected in two cases. However, the analysis was carried out
      on a small number of cells gained from paraffin slices, so it was impossible to
      meet the requirement to examine 300 interphase cell nuclei. Therefore, we
      recommend to always determine whether the material taken is representative enough
      for this methodology and whether the tissue fixation is not inadequate or
      insufficient.

PMID- 16955561
TI  - Sessile serrated adenomas of the large bowel. Clinicopathologic and
      immunohistochemical study including comparison with common hyperplastic polyps
      and adenomas.
AB  - Sessile serrated adenoma (SSA) is a newly characterized type of the large bowel
      adenoma. It arises in hyperplastic polyp (HP) and represents a precursor lesion
      of colorectal carcinoma with microsatellite instability. SSAs differ from common
      HPs by abnormal proliferation of the crypt epithelium and by nuclear atypia. We
      examined 15 SSAs from 15 patients. The age range was 25-80 years (average 60
      years). Six patients were females and 9 were males. For comparison, we examined
      10 conventional tubular adenomas and 10 common HPs with vesicular cells. The
      sites of SSAs were as follows: 8 in rectum, 4 in rectosigmoid colon, 1 in
      transverse colon, 1 next to mucinous carcinoma of ascending colon, 1 in
      anastomosis after resection of the transverse colon adenocarcinoma. The diameter
      of the lesions ranged from 5 to 12 mm. Histologically, SSAs showed asymmetrical
      proliferation of the epithelium, irregular shape of the crypts with their
      branching and some crypt dilatations especially in the basal parts of the crypts.
      Cellular atypia (dysplasia) was usually low. In 5 cases the nuclei were focally
      stratified and localized in the lower part of the cells. High-grade dysplasia was
      found only in SSA adjacent to mucinous adenocarcinoma. Immunohistochemically,
      SSAs showed secretion of gastrointestinal mucin expressing MUC2 and MUC5A. Both
      MUC2 and MUC5A were also positive in mucinous carcinoma. In previous studies
      these expressions were considered specific for serrated type of carcinogenesis.
      However, our study found positivity of MUC2 and MUC5A also in conventional
      adenomas. Expression of p53 in SSAs was minimal. SSAs have malignant potential
      comparable with conventional adenomas and for this reason they must be
      distinguished from HPs.

PMID- 16955563
TI  - Uterine tumor resembling ovarian sex cord tumor (UTROSCT). Report of case
      suggesting neoplastic origin of intratumoral myoid cells.
AB  - We report a case of double uterine tumor resembling ovarian sex cord tumor
      (UTROSCT). The tumor was composed of sex cord-like cords, nests and tubules, and
      bundles of myoid cells. The lesion was interesting especially in regard to
      histogenesis of intratumoral myoid cells. It is not known whether these cells are
      neoplastic or whether they represent preexisting myometrial smooth muscle cells
      entrapped into the tumor. In the present case, the sex cord-like epithelioid
      cells showed immunohistochemically myoid features in addition to features of
      epithelial, sex cord and endometrial stromal differentiation. The spindle cells
      expressed myoid, epithelial and endometrial stromal markers, but some of them
      were positive for sex cord marker calretinin. This immunophenotypic overlap
      between sex cord-like and myoid spindle elements indicates that the spindle cells
      of UTROSCT represent divergent line of differentiation of neoplastic cell rather
      than entrapped myometrial cells. It further expands the spectrum of possible
      differentiations in this polyphenotypic neoplasm.

PMID- 16955562
TI  - Leiomyoma of the gastrointestinal tract with intracytoplasmic inclusion bodies.
      Report of three cases.
AB  - We report three cases of leiomyoma of the gastrointestinal tract with
      intracytoplasmic inclusion bodies similar to those characteristic of inclusion
      body fibromatosis (IBF). The first two cases represent leiomyoma of the stomach:
      one in a 70-year-old female and the other in a 72-year-old female. In both
      instances inclusion bodies were present in a large amount. In the third case the
      leiomyoma was located in the esophagus of a 63-year-old male and inclusion bodies
      in this case were rare. In all three cases an immunohistochemical analysis showed
      positivity of the tumor cells for muscle specific actin HHF35 (MSA), alpha-smooth
      muscle actin (SMA), h-caldesmon and desmin. The first case showed some inclusion
      bodies with positivity for cytokeratin CAM 5.2 and focal weak positivity for
      cytokeratin 18. In the second case the inclusion bodies were positive at the
      periphery with antibodies directed against MSA and SMA. In the third case the
      inclusion bodies were immunohistochemically entirely negative. Ultrastructurally,
      the inclusion bodies in the first case were composed of aggregated filaments,
      some with entrapped cytoplasmic organels and others with finely granular dense
      cores.

PMID- 16955564
TI  - Low grade myofibroblastic sarcoma of tongue: a case report.
AB  - A case of a 24-year-old woman with a 6 weeks lasting nodule of the right margin
      of the tongue is described. The nodule was 20 mm in diameter and showed surface
      ulceration. The diagnosis of low grade myofibroblastic sarcoma was supported by
      histological, immunohistochemical and electronmicroscopic examination. Although
      the tumor resection was not complete, the patient is free of disease 1 year after
      operation. The differential diagnostics of low grade myofibroblastic sarcoma is
      discussed.

PMID- 16955566
TI  - Demonstration project claims 1 billion dollars in potential savings.
AB  - Savings would be realized if 76% of patients received most of quality measures.
      Numbers may be conservative, since participants had higher than average quality
      care. Premier offering P4P readiness program on the Internet free of charge.

PMID- 16955567
TI  - Project participants reaping the benefits.

PMID- 16955568
TI  - Leapfrog Group, N.J. Blues start recognition program.
AB  - Horizon looks to moderate some of the traditional tensions between hospitals,
      carriers. Program will not only offer financial incentives, but public
      recognition of top performers. Sponsors says program is one of the first P4P
      efforts to measure efficiency.

PMID- 16955569
TI  - Patients at this hospital have a 'ticket to ride'.
AB  - Strategy helps hospital comply with JCAHO's National Patient Safety Goals. Rapid
      cycle approach used to test, modify the structure of the form, checklists. Use of
      tickets helps transporters feel they are an integral part of the care team.

PMID- 16955570
TI  - Facility uses Six Sigma to improve quality.
AB  - Initiative demonstrates a 23% improvement in first bed assignment to a private
      isolation room. Keys to improvement found in enhanced communication and staff
      training. Staff develop reporting mechanism to sustain and institutionalize
      project results.

PMID- 16955571
TI  - Alliance seeks to improve cardiac care in hospitals.
AB  - Coalition says only 85% of patients receive care that meets basic quality
      measures. Awareness being raised of hands-on programs to help hospitals improve
      cardiac care. Hospitals performing below par will be approached with offers of
      assistance.

PMID- 16955572
TI  - [About fraud and creativeness...].

PMID- 16955573
TI  - [The importance of being different. Physician's role and nurse's role are tied
      together by the patient].

PMID- 16955574
TI  - [Anti-aging preparations--a lucrative industry. Immortality is a meaningless
      luxury, according to Darwin's theses].

PMID- 16955575
TI  - [Surgical treatment of atrial fibrillation. New methods may become routine
      procedures when performing heart surgery for other reasons].

PMID- 16955576
TI  - [Pre-eclampsia. A multi-organ disease which occurs in many pregnancies].

PMID- 16955577
TI  - [IVF in Sweden--continuous follow-up of children and mothers].

PMID- 16955578
TI  - [My personal experiences with the HELLP syndrome--two times].

PMID- 16955579
TI  - [The emergency admission misery--seen from the inside...].

PMID- 16955580
TI  - [Why this waiting time?].

PMID- 16955581
TI  - [There are no "overactive bladders"].

PMID- 16955582
TI  - [The finger and the moon--about apathetic children...].

PMID- 16955583
TI  - [The food industry salts too much].

PMID- 16955584
TI  - [Maybe Thomas Butler was judged by the circumstances].

PMID- 16955585
TI  - [Betapred is not so urgent].

PMID- 16955586
TI  - [Decubitus ulcer prevention as general indicator in external quality control:
      "Hospitals participate in a benchmarking comparison" (interview by Katrin
      Balzer)].

PMID- 16955587
TI  - [Hygiene Series: 14: MRSA infections: hand hygiene is the Achilles heel].

PMID- 16955588
TI  - [Biographical orientation in nursing of dementia: facilitating the approach to
      the patient].

PMID- 16955589
TI  - [Primary steps in introducing a quality management system: pediatric bridge
      project of the Dresden Uniclinic].

PMID- 16955590
TI  - [Health promotion in nursing between claims and reality--2: Exercise--a sign of
      life and vitality]].

PMID- 16955591
TI  - [Decubitus ulcer treatment: comparison between theory and general practice.
      Nursing care often not evidence based].

PMID- 16955592
TI  - [Decubitus ulcer prevalence and incidence in an intensive care unit of the UK S-H
      (Schleswig-Holstein University Clinic): confronting decubitus ulcer in a hospital
      wide manner].

PMID- 16955593
TI  - [Preventing decubitus ulcer in heart surgery interventions: visco-elastic foam
      layer on the operating room table--a study].

PMID- 16955594
TI  - [Decubitus ulcer prevalence and prevention in Germany and the Netherlands:
      differences and similarities].

PMID- 16955595
TI  - [Method mix in practical nursing education: using a multiplicity of learning
      approaches].

PMID- 16955596
TI  - [General practice instruction in the hospital--results of a nursing education
      study: structures are often still heterogeneous].

PMID- 16955597
TI  - [Status of implementing case management: delayed implementation].

PMID- 16955598
TI  - [From case to case: what really counts].

PMID- 16955599
TI  - [Prevention of ventilator-associated pneumonia: review of national and
      international guidelines].
AB  - Both in the USA and in Europe the most frequent hospital-acquired infection in
      intensive care units is the ventilator-associated pneumonia. Particularly,
      patients with artificial respiration are at risk. Their risk to acquire a
      nosocomial pneumonia is six to twenty-one times higher than for patients
      breathing without artificial help. Established risk factors are, amongst others,
      old age, tracheotomy or reintubation, defective immune functions, already
      existing pulmonary infections and lifestyle-dependent factors like smoking.
      Recent scientific results indicate that endogenous infections are the most
      important reason for the development of a ventilator-associated pneumonia.
      Infections are initiated by microaspiration of bacteria from the oropharynx.
      Bacterial colonisation of the mouth is often favoured by an increased gastric pH
      value, a secondary effect of the accompanying medicinal therapy. On a national as
      well as an international level there are evidence-based guidelines for the
      prevention of ventilator-associated pneumonia available. A comparison of
      guidelines of the US-American "Centers for Disease Control and Prevention" (CDC)
      with those of the German "Robert Koch-Institut" reveals deviating
      recommendations. Differences concern especially the changing of respiratory
      tubes, the use of filters and of closed humidifying systems. Additionally there
      are not yet recommendations for every aspect of infection prevention. However,
      recent studies show that regular surveillance of infections, further training of
      staff members and critically considering the invasive use of medical devices are
      able to reduce the rate of nosocomial infections and especially ventilator
      associated pneumonia.

PMID- 16955600
TI  - Who and what did Horton hear?

PMID- 16955601
TI  - Retention forces and seating discrepancies of implant-retained castings after
      cementation.
AB  - PURPOSE: The purpose of this in vitro study was to evaluate the influence of
      cement type and application technique on seating discrepancies and retention
      forces of noble alloy castings cemented on titanium abutments. MATERIALS AND
      METHODS: Eugenol-free zinc oxide (Freegenol), zinc phosphate (Harvard), glass
      ionomer (KetacCem), polycarboxylate (Durelon), and self-adhesive resin (RelyX
      Unicem) cements were used. The inner surfaces of the castings were either
      completely coated or half-coated with cement. Abutments were used as delivered
      with a machined surface for the first part of the study. Groups of 8 castings
      were cemented in both ways. For the second part of the study, the abutments were
      air-abraded (aluminum oxide, 50 microm particle size), and groups of 8 completely
      coated castings were cemented with all cements. Marginal discrepancies were
      measured before and immediately after cementation. Tensile tests were conducted
      to measure the retention forces. Statistical analysis was performed with pair
      wise comparison using the Wilcoxon rank sum test modified by Bonferroni-Holm.
      RESULTS: Change in seating discrepancies did not differ significantly among the
      different application techniques. The median retention forces for completely
      coated castings were 177 N for eugenol-free zinc oxide, 346 N for zinc phosphate,
      469 N for glass ionomer, 813 N for polycarboxylate, and 653 N for self-adhesive
      resin. With respect to retention force, 3 significantly different groups (P <
      .05) were identified: (1) zinc oxide, (2) zinc phosphate/glass ionomer, and (3)
      polycarboxylate/self-adhesive resin. No differences in retention between the 2
      coating techniques were found for any cement. However, air abrading the abutments
      resulted in increased retention of the castings for some of the cements.
      CONCLUSIONS: Half-coating of the restorations with cements did not result in
      reduced retention values compared to the complete coating technique, but air
      abrasion resulted in increased retention with some cements.

PMID- 16955602
TI  - Tissue engineering of a periodontal ligament-alveolar bone graft construct.
AB  - PURPOSE: This paper reports on a 2-phase study of a novel membrane-scaffold graft
      construct, its ability to support periodontal ligament fibroblast (PDLF) and
      alveolar osteoblast (AO) growth in vitro, and its use for tissue engineering a
      PDL-AO interface in vivo. MATERIALS AND METHODS: Human PDLFs were seeded onto
      perforated poly(epsilon-caprolactone) membranes (n=30) at 78,000 cells/cm2; human
      AOs were seeded on poly(epsilon-caprolactone) scaffolds (n=30) with fibrin glue
      at 625,000 cells/cm3. Cell attachment, morphology, viability, and metabolic
      activity were monitored for 3 weeks in vitro. Subsequently, cell-seeded membrane
      scaffold constructs (experimental group, n=9) and nonseeded constructs (control
      group, n=4) assembled with fibrin glue were implanted subcutaneously into 7
      athymic mice for 4 weeks. RESULTS: PDLFs formed confluent layers on membranes,
      whereas AOs produced mineralized matrices within scaffolds upon osteoinduction in
      vitro. Well-vascularized tissue formation was observed after implantation.
      Integration at the membrane-scaffold interface was enhanced in the experimental
      group. Type I collagen, type III collagen, fibronectin, and vitronectin were
      found adjacent to membranes and within constructs. Bone sialoprotein expression
      and bone formation were undetectable. DISCUSSION: Membrane perforation and
      scaffold porosity facilitated tissue integration and vascularization at the
      construct-recipient site. However, the interaction between PDLF and AO could have
      interfered with osteogenesis at the interface of soft and mineralizing tissues.
      CONCLUSIONS: Both matrices supported PDLF and AO attachment and proliferation in
      vitro. The membrane-scaffold construct facilitated tissue growth and
      vascularization while providing strength and form in vivo.

PMID- 16955603
TI  - Immunohistochemical analysis of cortical and cancellous bone after radiation and
      the effect of platelet-rich plasma on autogenous bone grafting.
AB  - PURPOSE: The collection of autologous platelet-rich plasma (PRP) has demonstrated
      favorable affects on wound healing in compromised patients. The purpose of this
      study was to evaluate the expression of PDGF, bFGF, and TGF-beta in irradiated
      and nonirradiated bone in a rabbit tibia model and the ability of PRP to increase
      growth factor expression when added to autogenous bone graft in a rabbit cranial
      defect model. MATERIALS AND METHODS: Ten New Zealand White rabbit tibiae and
      calvariae were utilized for this study. Tibiae were irradiated at 60 to 70 cGy
      and evaluated for expression of PDGF, bFGF, and TGF-beta. Rabbit calvariae were
      also analyzed after grafting with autogenous bone and PRP for determination of
      growth factor expression. RESULTS: Decreased expression of PDGF, bFGF, and TGF
      beta was seen in cortical and cancellous bone samples when irradiated bone was
      compared to nonirradiated rabbit tibiae. An increase in PDGF, bFGF, and TGF-beta
      expression was detected in cortical autogenous bone grafts with PRP at 1 and 2
      months compared to autogenous bone alone. DISCUSSION: In this study, growth
      factors, which were decreased in irradiated cortical and cancellous bone, showed
      increased expression at 1 and 2 months when PRP was added to autogenous bone
      grafts. Thus, PRP may have potential therapeutic applications when bone grafting
      is required in patients with reduced bone vascularity, including patients with
      previous head and neck irradiation, diabetes, and smoking habits. CONCLUSIONS:
      Decreased expression of PDGF, bFGF, and TGF-beta was seen in radiated rabbit
      tibia as compared to nonirradiated controls, and increased expression of these
      growth factors was seen in PRP-containing autogenous bone grafts.

PMID- 16955604
TI  - Correlations between clinical parameters and interleukin-6 and interleukin-10
      levels in saliva from totally edentulous patients with peri-implant disease.
AB  - PURPOSE: The purpose of the present study was (1) to assess the relationship
      between clinical parameters and concentrations of the proinflammatory cytokine IL
      6 and the anti-inflammatory cytokine IL-10 in the saliva of totally edentulous
      patients with implant-supported overdentures; (2) to assess whether estimation of
      IL-6 and IL-10 levels in saliva could be a useful laboratory tool to detect
      changes preceding serious clinical complications. MATERIALS AND METHODS: Thirty
      healthy adult volunteers (14 men and 16 women) with implant-supported
      overdentures were recruited from Tallinn Dental Clinic. The biochemical and
      clinical parameters evaluated were the levels of IL-6 and IL-10 in saliva, pocket
      probing depth (mm), Gingival Index (0,1, 2, or 3), and bleeding on probing (0 or
      1). RESULTS: The level of IL-6 in saliva in the peri-implant disease group was
      significantly elevated compared to the healthy group. IL-10 could be detected
      only in the saliva of patients with peri-implant disease, and it did not appear
      at detectable amounts in saliva of healthy controls. In addition, the levels of
      IL-6 and IL-10 in peri-implant disease group were positively correlated with
      clinical parameters. CONCLUSIONS: These data suggest that a significant
      relationship exists between the amount of a proinflammatory cytokine (IL-6) and
      the inflammatory response in peri-implant tissue. The results also suggest that
      IL-6 and IL-10 could be used as markers of peri-implant disease together and that
      the level of the latter cytokine gives additional information about the potency
      of an organism's integrated immune response for maintenance of inflammatory
      balance.

PMID- 16955605
TI  - Healing in smokers versus nonsmokers: survival rates for sinus floor augmentation
      with simultaneous implant placement.
AB  - PURPOSE: Evidence suggests that smoking is detrimental to the survival of dental
      implants placed in grafted maxillary sinuses. Studies have shown that improving
      bone quantity and quality, using rough-surfaced implants, and practicing good
      oral hygiene may improve outcomes. In this prospective study, the long-term
      survival rates of implants placed simultaneously with sinus grafting in smokers
      and nonsmokers were compared. MATERIALS AND METHODS: Implants with roughened
      surfaces were immediately placed into maxillary sinus grafts in patients with 1
      to 7 mm of residual bone. A total of 2132 simultaneous implants were placed into
      the grafted sinuses of 226 smokers (627 implants) and 505 nonsmokers (1505
      implants). A majority of the patients received a composite graft consisting of
      50% autogenous bone. In both smokers and nonsmokers, approximately two thirds of
      the implants had microtextured surfaces; the remainder had hydroxyapatite-coated
      surfaces. The implants were restored and monitored during clinical follow-up for
      up to 9 years. RESULTS: Cumulative survival of implants at 9 years was 97.9%.
      There were no statistically significant differences in implant failure rates
      between smokers and nonsmokers. DISCUSSION: Implant survival was believed to
      depend on the following aspects of the technique used: creation of a large buccal
      window to allow access to a large recipient site; use of composite grafts
      consisting of at least 50% autogenous bone; meticulous bone condensation;
      placement of long implants (i.e., 15 mm); use of implants with hydroxyapatite
      coated or microtextured surfaces; use of a membrane to cover the graft and
      implants; antibiotic use and strict oral hygiene; use of interim implants and
      restricted use of dentures; and adherence to a smoking cessation protocol.

PMID- 16955606
TI  - Primary stability of a conical implant and a hybrid, cylindric screw-type implant
      in vitro.
AB  - PURPOSE: The differences with respect to primary stability between 2 Camlog
      implants, a conical implant, and a hybrid cylindric screw-type implant, were
      investigated in vitro. The effect of underdimensioned implant bed preparation was
      also studied for both implant designs. MATERIALS AND METHODS: In an in vitro
      model the stability of different implants in fresh porcine iliac bone blocks was
      measured using torque moment values, the Periotest, resonance frequency analysis,
      and push-out testing. RESULTS: The conical implant showed significantly higher
      primary stability than the cylindric hybrid implant using the insertion torque,
      Periotest, and push-out tests. For both types of implants, the torque moment
      values following under-dimensioned preparation were significantly better than
      those obtained following the standard drilling protocol (Conical: 25.00 vs 11.00
      Ncm; Cylindrical: 11.75 vs. 5.75 Ncm). For the cylindric implant, significantly
      better results following under-dimensioned implant bed preparation were observed
      only with the insertion torque and the pushout testing values. The mean ISQ
      values for all groups were between 55 and 57; no statistical differences with
      respect to ISQ could be found. CONCLUSION: In this in vitro model conical
      implants showed higher primary stability than cylindric implants. The procedure
      of under-dimensioned drilling seemed to increase primary stability for both types
      of implants; however, the effect was only observable using insertion torque. RFA
      and Periotest, the noninvasive, clinical methods tested, did not clearly
      demonstrate this difference.

PMID- 16955607
TI  - Fixed partial prostheses supported by 2 or 3 implants: a retrospective study up
      to 18 years.
AB  - PURPOSE: The purpose of this study was to evaluate and compare the long-term
      performance of fixed partial prostheses supported by 2 or 3 implants. MATERIALS
      AND METHODS: All patients treated with fixed partial prostheses supported by
      either 2 or 3 implants during the period 1985 to 1998 were included in this
      retrospective report. Annual clinical follow-up examinations were performed, with
      special attention to stability of the prostheses and peri-implant and occlusal
      conditions. Radiographic examination was performed when the prostheses were
      delivered (year 0) and subsequently at 1-year, 5-year, and 10-year examinations.
      RESULTS: A total of 178 patients had received fixed partial prostheses (FPPs)
      during this period of whom 123 (77 women and 46 men) were available for follow-up
      (mean age = 65 years, range 32-91). These 123 patients received a total of 146
      implant-supported FPPs (63 two-implant- and 83 three-implant-supported) supported
      by 375 implants. The mean observation periods for the 2- and 3-implant-supported
      restorations were 9.6 years and 9.4 years (range, 5 to 18 years), respectively.
      Survival rates for the 2- and 3-implant-supported prostheses were 96.8% and
      97.6%, respectively. The implant survival rate after loading was 98.4% for both
      groups. The mean bone loss at the 5-year follow-up was 0.3 mm for the 2 groups.
      No significant differences in bone loss (P > .05), implant failure rate (P >
      .05), or incidence of mechanical complications (P > .05) were found between the 2
      prosthesis designs. The complications differed, significantly, with more loose
      gold and abutment screws in the 2-implant-supported group (P < .05) and more
      porcelain fractures in the 3-implant-supported group (P < .05). CONCLUSION: The 2
      implant-supported partial prostheses exhibited long-term clinical performance
      comparable to prostheses supported by 3 implants.

PMID- 16955608
TI  - An in vitro evaluation of titanium, zirconia, and alumina procera abutments with
      hexagonal connection.
AB  - PURPOSE: The purpose of this study was to assess the precision at the implant
      interface of titanium, zirconia, and alumina Procera abutments with a hexagonal
      connection for single-tooth restorations. MATERIALS AND METHODS: Twenty Procera
      abutments were produced with commercially pure titanium, 20 with zirconia, and 20
      with alumina using computer-assisted design and manufacture (CAD/CAM). The
      rotational freedom of the abutments was assessed to detect the precision of fit
      of each abutment on the top of the implant hexagon. RESULTS: Significant
      differences relative to rotational freedom were found between groups: the
      titanium group and the zirconia group did not differ significantly, but both
      demonstrated significantly smaller mean rotational freedoms than the alumina
      group (P < .05). Rotational freedom was less than 3 degrees for all abutments.
      CONCLUSIONS: The hexagonal misfit of the Procera abutment on the implant hexagon
      may be implicated in screw joint loosening. In the present study, all types of
      CAD/CAM Procera abutments consistently showed less than 3 degrees of rotational
      freedom in a situation where the abutment was connected to an implant by a
      hexagonal external connection.

PMID- 16955609
TI  - Macroanatomic and radiologic characteristics of the superior genial spinal
      foramen and its bony canal.
AB  - PURPOSE: To determine the incidence, size, location, course, and content of the
      superior genial spinal foramen and its bony canal. MATERIALS AND METHODS: Three
      hundred eighty dry human cadaver mandibles were morphometrically analyzed by
      measuring the distance from the foramen to the mandibular base and the size of
      the foramen and bony canal. Radiologically, the course of the bony canal and its
      relation to the mandibular incisive canal were investigated after injecting
      contrast medium (Omnipaque) in the superior genial spinal foramen and the
      incisive canal at the level of the mental foramen or by inserting a thin metal
      wire into the bony canal. Dissection was performed on another 10 intact cadaver
      mandibles. RESULTS: A distinct foramen was present in 98% of all dry specimens
      studied. Its general form was round or flattened funnel-shaped. Upon
      microanatomic dissection, a distinct branch of the lingual artery and the lingual
      nerve entering the superior genial spinal foramen were found. CONCLUSIONS: The
      superior genial spinal foramen is present in most human mandibles and appears to
      be the entrance of a true lingual neurovascular bundle passing into the bone via
      a well-defined bony canal toward the buccal side. This implies that surgery and
      more specifically implant placement at the mandibular midline may carry some risk
      of neurovascular damage.

PMID- 16955610
TI  - Comparison of 7 luting protocols and their effect on the retention and marginal
      leakage of a cement-retained dental implant restoration.
AB  - PURPOSE: To determine the cement bond strength and marginal leakage of castings
      cemented to implant abutments. MATERIALS AND METHODS: Fifty-six titanium
      abutments and castings were divided into 7 groups (n=8), 1 for each cement.
      Castings were cemented to abutments using 1 of 3 resin-based cements (RES, RES-B,
      and RES-B-P), a resin-modified glass ionomer (GI), a polycarboxylate cement
      (PCB), an acrylic urethane cement (UDM), or a zinc phosphate cement (ZP).
      Specimens were placed in 100% humidity at 37 degrees C for 24 hours. Specimens
      were subjected to compressive load cycling followed by thermal cycling; they were
      then immersed for 24 hours in 0.5% basic fuchsin. Castings were removed with an
      Instron universal testing machine with a crosshead speed of 0.125 cm/min. Leakage
      was visually graded from 0 (no leakage) to 2 (leakage extended beyond the lower
      half of the internal surface of the casting). Failure load (FL) was analyzed with
      analysis of variance and Scheffe's test (alpha = .05). Chi-square was used to
      analyze leakage (alpha = .05). RESULTS: Cements were categorized by FL into 4
      statistically unique groups: (1) RES-B-P (351 N) and GI (337 N); (2) ZP (245 N)
      and RES-B (241 N); (3) PCB (107 N); and (4) RES (63 N) and UDM (55 N). Leakage
      was greater for the PCB group than for the other groups (7 of 8 specimens
      demonstrated leakage; P < .01). Three ZP specimens demonstrated leakage. UDM and
      RES each had 1 specimen with leakage. RES-B-P, RES-B, and GI showed no leakage.
      CONCLUSIONS: Luting agents designated by the manufacturer as provisional cements
      demonstrated lower resistance to removal, regardless of material type. Luting
      agents described by manufacturers as "permanent" differed in resistance, with
      resin cements being most resistant, followed by zinc phosphate and
      polycarboxylate cements. Provisional cements demonstrated leakage comparable to
      higher-strength materials.

PMID- 16955611
TI  - Marginal integrity of direct and indirect castings for implant abutments.
AB  - PURPOSE: Current implant systems with screw-retained abutments permit direct
      laboratory fabrication of castings. Computer aided drafting systems further
      enhance the fabrication of computer-milled abutments (CMAs) and castings. The
      purpose of this study was to compare marginal accuracy, as measured by gap size,
      of castings made directly on CMAs with those made indirectly on epoxy and stone
      dies. MATERIALS AND METHODS: Castings were made directly for 10 CMAs. Marginal
      gap measurements were made with the castings seated on the abutments (group A).
      Castings were also made indirectly on stone and epoxy dies obtained from
      impressions of the abutments. Marginal gap measurements were made with these
      indirectly made castings seated on their CMAs (groups B and E). In addition, the
      directly made castings were transferred between CMAs and marginal gap
      measurements made (group D). Marginal gap measurements of the groups were
      compared with analysis of variance (ANOVA) and pair-wise comparisons (Scheffe
      test). RESULTS: Groups A and D had marginal gaps of less than 100 microm. These
      marginal gaps were significantly smaller (P < .05) than the gaps of groups B and
      E, made on dies, which were approximately 200 to 500 microm. DISCUSSION AND
      CONCLUSIONS: With CMAs, it is possible to make an exact duplicate of the
      abutment. This permits the laboratory to make castings on duplicate abutments
      with greater precision than can be obtained using the indirect technique. Direct
      fabrication of castings resulted in smaller marginal gaps, which in turn allows a
      better marginal seal and improved retention of castings.

PMID- 16955612
TI  - Vertical bone augmentation with dental implant placement: efficacy and
      complications associated with 2 different techniques. A retrospective cohort
      study.
AB  - PURPOSE: To compare retrospectively the efficacy of and complications associated
      with 2 different techniques for vertical bone augmentation at implant placement:
      autogenous particulated bone grafts covered either by nonresorbable titanium
      reinforced e-PTFE barriers or by resorbable collagen barriers supported by
      osteosynthesis plates. MATERIALS AND METHODS: Nineteen partially edentulous
      patients were consecutively treated: 11 patients had 18 implants treated for
      vertical bone augmentation with nonresorbable barriers, whereas 8 patients had 11
      implants treated with resorbable barriers supported by osteosynthesis plates. Two
      independent assessors evaluated the amount of tissue regenerated and
      complications based on photographs and/or radiographs. RESULTS: No implants
      failed. In the group treated with nonresorbable barriers, complete bone
      regeneration was obtained for 12 of 18 implants. More than 50% of the planned
      regeneration was obtained for the remaining 6 implants. One patient had a
      dehiscence with suppuration that required an additional surgical intervention to
      remove the barrier. For resorbable barriers, complete regeneration was obtained
      for 10 of 11 implants. Dehiscences occurred in 2 patients. In 1 case no treatment
      was necessary. The other patient was treated with applications of chlorhexidine
      gel; more than 50% of the desired bone regeneration was obtained. DISCUSSION AND
      CONCLUSIONS: No statistically significant differences for the amount of
      regenerated tissue and complications were observed between the 2 techniques;
      however, the power of the study was too low to detect a difference, if any.
      Randomized clinical trials with a sufficient number of patients are needed to
      determine which could be the most effective technique for vertical ridge
      augmentation.

PMID- 16955613
TI  - Private practice results of screw-type tapered implants: survival and evaluation
      of risk factors.
AB  - PURPOSE: The aims of this study were to examine the long-term survival and the
      prosthetic treatment outcome of screw-type, tapered implants placed in a private
      practice setting and to explore potential risk factors of implant failures.
      MATERIALS AND METHODS: In this retrospective analysis of patients treated with
      endosseous screw-type tapered implants, data relative to implant placement and
      failure, implant length, location, prosthetic treatment, medical history, smoking
      habits, and oral health behavior were gathered by chart review and questionnaire.
      An oral examination was also conducted. Cumulative survival rates were estimated
      through Kaplan-Meier methods. Comparisons between subgroups of patients were made
      using the log-rank statistical test. The association between several factors and
      implant failures was analyzed using Cox regression analyses (random and dependent
      models). Differences were considered significant when P < .05. RESULTS: The
      survival rate of 663 implants placed in 159 patients (65 men, 94 women; 80.7% of
      197 eligible patients) was 91.8% after 120 months. Mandibular implants had a
      higher survival rate than maxillary implants (96% versus 89%, P = .011). The
      failure rates for implants were 15.0% among current smokers, 9.6% among former
      smokers, and 3.6% among nonsmokers. The differences between nonsmokers, former
      smokers, and current smokers were significant (nonsmokers versus former smokers:
      P = .036, nonsmokers versus current smokers: P < .001, former smokers versus
      current smokers: P = .003). Only number of years of smoking was significantly
      associated with an increased risk of implant failures (P = .036 using dependent
      estimation; P = .004 using independent estimation). The HR increased to 6.6 for
      patients who had smoked for 45 years. Loosening of prosthetic components were
      rare (n=12). No fractures of screws or implants were found. DISCUSSION: Higher
      failure rates for former smokers and a dose-response effect between duration of
      smoking and implant failure rates suggested that permanent tissue damage from
      smoking may occur in addition to immediate local and systemic effects. The
      frequency of prosthetic complications was comparable to other studies.
      CONCLUSIONS: Screw-type tapered implants placed in a private dental office
      demonstrated a cumulative survival rate of 91.8%. The relative risk of implant
      failure increased with the duration of smoking.

PMID- 16955614
TI  - A new device in immediately loaded implant treatment in the edentulous mandible.
AB  - PURPOSE: This article reports preliminary clinical results of the Speed Master
      system, a method for immediate loading of implants for the treatment of
      mandibular edentulism. MATERIALS AND METHODS: Fifteen patients with edentulous
      mandibles were consecutively included in the study. Each received 4 implants
      between the mental foramina placed using the system's surgical guides. Permanent
      fixed prostheses fabricated over premanufactured titanium bars were attached to
      the implants on the day of implant placement. The patients were followed for 15
      to 27 months (mean, 19 months). Peri-implant tissues were periodically evaluated.
      Marginal bone loss was monitored with periapical radiographs using a computerized
      technique. Satisfaction was assessed by means of a questionnaire. RESULTS: The
      overall implant and prosthetic survival rates were 100%. At the time of the final
      follow-up visit, mean marginal bone loss was 1.11 mm, and bleeding on probing was
      not observed. Only 6.7% of the patients reported any discomfort during treatment,
      and all patients would recommend the procedure to others. DISCUSSION: The
      immediate loading of implants placed in the edentulous mandible with the Speed
      Master surgical and prosthetic protocol reduces treatment time and number of
      surgical procedures in comparison to classic delayed loading protocols.
      CONCLUSION: The rehabilitation of the mandible with an immediately delivered
      occlusally loaded hybrid prosthesis supported by 4 implants does not appear to
      jeopardize the success of the osseointegration and represents a viable treatment

PMID- 16955615
TI  - Early healing events following placement of a palatal subperiosteal orthodontic
      anchor: a pilot study.
AB  - PURPOSE: The aim of this report was to describe the initial 8-month healing
      events of 8 consecutive cases of placement of an onplant device for orthodontic
      anchorage and to report the results of a questionnaire evaluating subjective
      patient experience. METHODS: At 2 weeks and at 4 and 8 months after placement of
      the device, presence or absence of exposure of the device, mobility using gentle
      finger palpation, and signs of possible inflammation were evaluated. At 8 months,
      the inflammatory status of the tissue-abutment interface was determined from
      presence or absence of bleeding and/or suppuration on probing. Patients'
      experience of pain, discomfort, and acceptance of the treatment were evaluated by
      the use of visual analog scales. RESULTS: In 7 of the 8 patients, the device
      became stable and could be used for orthodontic anchorage. In 1 case, infection
      occurred, and the device was removed. At the 8-month time point, none of the 7
      successful devices showed any plaque or any bleeding or suppuration on
      stimulation with a periodontal probe. Most patients reported little
      pain/discomfort from the various treatment procedures and indicated that they
      felt that opting for the onplant treatment had been the right choice. CONCLUSION:
      The results of this pilot study suggest that placement of the onplant can lead to
      uneventful healing and stability of the device. Further studies with larger
      numbers of subjects are necessary to substantiate these findings and to determine
      the usefulness of this device for orthodontic anchorage.

PMID- 16955616
TI  - Radiographic and surgical template for placement of orthodontic microimplants in
      interradicular areas: a technical note.
AB  - PURPOSE: In recent years, microimplants have gained popularity in orthodontics.
      Microimplants are primarily placed in complex sites where critical anatomic
      structures, such as roots of teeth, may be damaged, so precise surgical planning
      is required prior to placement. The goal of this report was to introduce a newly
      developed technique for the placement of microimplants in interradicular areas
      and evaluate its accuracy. MATERIALS AND METHODS: The planned placement site is
      radiographed using a radiographic template and film holder fabricated by the
      investigators. The resultant radiograph is clipped and attached to the
      radiographic template to make a surgical template to guide the placement of the
      microimplant. Forty-one patients, 15 men and 26 women ranging in age from 21 to
      29 years, were enrolled in this study. On 1 side of the arch, this novel
      technique was used for implant placement, and on the other side, an established
      method reported by Maino and associates (i.e., the control technique) was used.
      RESULTS: A total of 116 microimplants 2 mm wide and 9 mm long were placed
      interradicularly in 41 patients. Twelve of 58 microimplants were placed
      unsuccessfully in the control group, versus 2 of 58 in the test group.
      Statistical analysis showed that there was a significant difference between the 2
      techniques in terms of success rate (P < .05). DISCUSSION: Presurgical diagnosis
      of bone quantity and transfer of the information to the surgical sites are vital
      in microimplant placement. Radiographic templates modified for surgical purposes
      have the advantage of transferring radiographic information directly to the
      surgical site. CONCLUSION: This study, although limited in some respects,
      demonstrated that microimplant placement can be improved using the newly
      developed technique described.

PMID- 16955617
TI  - Simplified onlay grafting with a 3-dimensional block technique: a technical note.
AB  - Block allografts can serve as effective alternatives to block autografts but are
      more brittle and can easily break if not properly contoured to fit the defect
      site. The need to make such preparations during surgery can prolong the invasive
      procedure and may result in a less-than-optimum graft preparation that can
      compromise success. The sterile 3D block technique allows block allografts to be
      prepared and attached to a stereolithography model of the patient's jaw prior to
      surgery and then stored in a sterile environment until surgical delivery.

PMID- 16955618
TI  - [The future is chronic].

PMID- 16955619
TI  - [New perspectives in the primary care of the chronically ill--against the
      "tyranny of the urgent". Part 1: chronic diseases as a challenge for primary
      care].
AB  - Chronic diseases and multimorbidity are becoming a fundamental challenge for
      primary care which already requires a very high input of resources. Due to their
      broad range and continuity, general practices play a major role, but are poorly
      prepared to succeed in the structured healthcare of chronically ill patients. The
      reality of care in everyday practice is primarily characterized by the 'tyranny
      of the urgent', and such a reaction to acute problems leads to noticeable
      deficits in permanent care. Part one of a two-part article series asks to what
      extent demographic changes and medical progress are responsible for this
      development. Meanwhile, a large quantity of empirical evidence indicates that
      results improve when case management is implemented for chronically ill patients.
      Though disease management programs are being increasingly established in Germany,
      many general practices are only poorly prepared for their tangible implementation
      in everyday routine. The comparison of two case studies shows how the primary
      care of chronically ill patients might look like in the future. On the basis of
      both scientific evidence and the globally acknowledged 'Chronic Care Model', part
      two of the article looks at sustainable strategies and special tools which allow
      for an adequate care of chronically ill patients in general practice.

PMID- 16955620
TI  - [New perspectives in the primary care of the chronically ill--against the
      "tyranny of the urgent". Part 2: The chronic care model und case management as
      the basis of a forward-looking approach to primary care].
AB  - Family medicine remains strongly influenced by reactive medicine ('tyranny of the
      urgent') and the fragmentation of healthcare associated with it. In the first
      part of the present article the increasing practical and economic relevance of
      chronic diseases and multimorbidity were analyzed as a fundamental challenge for
      primary care and family medicine in particular. Part two describes a forward
      looking approach to guidelines and special tools which are able to guide and
      support future healthcare tasks of general practice. Wagner's Chronic Care Model,
      which was developed on the basis of numerous controlled studies, integrates
      empirical results, theoretical ideas and real experience within a comprehensive
      concept for the treatment of chronic diseases. The model focuses on
      the'productive interaction' between an active patient and a proactive practice
      team. The various elements of the model help to better understand healthcare in
      general practices, for example by establishing reminder and recall systems by
      means of a structured reorganization, through patient registers, the
      implementation of consultation hours for chronically ill patients as well as
      patient training. 'Case management' is essential to the success of structured
      care. Taking care of patients with major depression as an example, it is
      demonstrated how case management through practice assistants in general practices
      enables the individual needs of chronically ill patients to be better taken into
      account. The professionalism of the practice team with new roles and task sharing
      as well as the implementation of modern strategies for the care of chronically
      ill patients provide a new chance and a sharpened profile for general practices
      of the future.

PMID- 16955621
TI  - [Effectiveness of German disease management programs--problems of clinical
      evaluation research in the light of a study protocol].
AB  - Since 2002 some of the world's largest disease management programs have been
      launched in Germany--initially for type II diabetes and coronary heart disease-
      with approximately 5 million eligible insured persons and (in 2005) 2.04 million
      registered participants. The programs were not piloted prior to their start, and
      the prescribed statutory evaluation cannot be expected to result in an
      effectiveness validation. The article describes the development of a study
      protocol for a randomized controlled trial. It also discusses methodological
      problems, in particular the definition of primary target criteria, the guarantee
      of a 'naturalistic' intensity of intervention, and the creation of a control
      group during nation-wide implementation. Due to lacking support from the
      stakeholders the proposed randomized trial could not be implemented. Its design,
      however, allows the required standards for the program evaluation to be
      specified.

PMID- 16955622
TI  - [The future is chronic: German primary care and the Chronic Care Model--The
      comprehensive principles in the proactive treatment of the chronically ill].
AB  - BACKGROUND: In Germany, primary healthcare for patients with chronic diseases
      needs to be improved. Taking the example of depression, congestive heart failure,
      diabetes and diseases of the musculoskeletal system we analyzed to which extent
      the 'Chronic Care Model' allows for improvements. METHODS: Diagnosis-specific
      health assessment; adaptation of the 'Chronic Care Model' to the German
      healthcare system; peer reviewed discussions of the potentials for improving
      primary care of the chronically ill. RESULTS/DISCUSSION OF THE HEALTHCARE
      SITUATION: 1) Diagnosis and therapy of chronic diseases comply insufficiently
      with the evidence. 2) Patients are too passive and/or receive only little
      effective support. 3) Treatments are often uncoordinated and fragmented. 4) The
      follow-up of treatment results is often neglected. 5) Approaches to indicated
      diseases are promising. CONCLUSIONS: The'Chronic Care Model' could improve
      chronic care in Germany. Disease Management Programs (DMP) should amend
      multimorbidity and individual healthcare and/or facilitate implementation in
      general practice.

PMID- 16955623
TI  - [The "Depression Monitoring list" (DeMoL) with integrated PHQ-D-Rationale and
      design of a tool for the case management for depression in primary care].
AB  - BACKGROUND: Structured and regular monitoring and/or case management support
      treatment continuity of patients with depression in primary care. Central tools
      are questionnaires with stratified operating instructions. Questions should be
      geared towards treatment relevance in primary care and identify clinical
      parameters in a reliable and valid manner and in due time. Stratified information
      transfer to the general practitioner should be objective to ensure patient
      related communication in the practice team. METHOD: Development of a draft tool
      based on evidence-based guidelines, peer-reviewed pre-test, practice test among
      users. RESULT: The Depression Monitoring List (DeMoL) with integrated PHQ-D for
      interviews with depressive patients to be conducted by practice assistants
      assesses 1.)'clinical diagnosis' and 2.) 'patient adherence' and 3.) governs the
      information flow in the practice via a 'robot scheme'. Users (doctors and
      practice assistants) evaluated the tool as practicable and relevant for patient
      care in family practices. Experiences gained can also be used for the treatment
      of other chronic diseases.

PMID- 16955624
TI  - [The implementation of evidence-based medicine in general practice-acceptance and
      use of external information services].
AB  - BACKGROUND: The demand for, and the potential of, evidence-based medicine (EBM)
      in everyday general practice have not been studied systematically yet. METHODS:
      For six months we offered all general practitioners (n = 190) practising in one
      of Berlin's city districts to conduct a systematic search for, and critical
      assessment of, the medical literature on any patient-related questions that
      participating physicians might have had. The primary aim of the study was to
      motivate general practitioners to ask patient-related questions and, in the long
      run, to integrate EBM into their medical practice. At the end of the project,
      attitudes towards EBM were assessed using standardized questionnaires. RESULTS:
      Only four questions, all referring to the field of therapy/prevention, were asked
      by the general practitioners in the district in which we offered our services.
      The average time required to supply an answer was 6.25 hours. For the subsequent
      evaluation of the service, the response rate was 34%. Reasons for not taking
      advantage of the service included lack of time, doubts about how the questioner
      would benefit from the service, and "being unaware" of the offering. CONCLUSIONS:
      Only rarely did general practitioners make use of the research service offered.
      The reasons included lack of time and the general practitioners' doubts that the
      service would be of benefit to their patients. In addition, we cannot exclude the
      possibility that the project may not have been adequately integrated into
      physicians' everyday practice. Nevertheless, the participants indicated that they
      were interested in EBM and that they considered scientific or evidence-based
      information to be relevant to the care of patients. This is why it is important
      to develop some type of continuing medical education model that can be
      effectively integrated into everyday medical practice.

PMID- 16955625
TI  - [Oversized patient arms: a problem with blood pressure measurements].
AB  - The increase in the worldwide prevalence of obesity systematically leads to a
      higher number of individuals who may be wrongly diagnosed as hypertensive because
      their arms are too large for standard blood pressure cuffs, which are ordinarily
      appropriate in patients with normal sized arms. The aim was to gain real data of
      upper arm and wrist circumferences in 327 elected subjects with larger arms
      (upper arm circumference >32.5 cm) from two Bavarian general practices. We found
      that 93.9% of all patients had an upper arm circumference of a maximum of 41.0 cm
      and a wrist circumference of at most 20.5 cm. These data were then compared with
      the approved size ranges of six wrist blood pressure measurement devices, one
      special three-in-one cuff for different sizes and the two large adult cuffs
      recommended by the German Hypertension Society. Availability of one large cuff
      and one wrist blood measurement device (either used at the upper arm or at the
      wrist depending on patient dimensions) seems to be sufficient. This should allow
      for true blood pressure readings to be obtained in at least 96% of all patients
      with arms of more than normal circumference.

PMID- 16955626
TI  - [Prognosis for diabetes].

PMID- 16955627
TI  - [Opinion on "New perspective in general medical care of chronic disease--again
      the dominance of urgency"].

PMID- 16955628
TI  - [A pioneer turns homeward: Society of Development and Continuing Education
      developer Thilo Kober goes back down under].

PMID- 16955629
TI  - [Xerostomia].

PMID- 16955630
TI  - Evaluation of a microparticle enzyme immunoassay for the measurement of sirolimus
      in whole blood (Abbott IMx sirolimus).
AB  - An immunoassay of sirolimus based on the microparticle enzyme immunoassay (MEIA)
      principle was evaluated on 105 whole blood samples (EDTA) drawn from a population
      of renal (n = 38) and hepatic or heart (n = 3) transplant patients. Each blood
      sample was analyzed simultaneously by MEIA and by a liquid chromatography mass
      spectrometry (LC-MS) method. The statistical analysis according to Passing-Bablok
      (x= LCMS, y= mean of two measurements of the same samples on IMx) produced the
      following results: Spearman r value = 0.9651, y(MEIA) = 0.99x (LCMS) - 0.26
      microg/l. The analytical performance of the MEIA method showed a CV < or = 10%
      and a lower limit of quantification of 1.5 microg/l, which are acceptable for
      routine clinical monitoring. In conclusion, the MEIA method has shown robust,
      stable and reproducible features with an excellent correlation with the LC-MS
      method.

PMID- 16955632
TI  - Problems with the external quality assessment of accuracy of point of care
      devices (POCD) for blood glucose are independent of sample composition.
AB  - This short article describes the results obtained in both internal and external
      quality assessment of point of care devices (POCD) for the monitoring of blood
      glucose. The results show that the use of synthetic, serum and whole blood
      matrices for the samples do not markedly change the inaccuracy of measurement. It
      is only possible to check precision of POC devices for glucose in external
      quality assessment (EQA) surveys for POC devices for blood glucose. The majority
      of devices used in point of care testing for blood glucose had acceptable
      (im)precision. The applications and limitations of the use of POC devices for
      blood glucose must be clearly defined before allowing their use in patient care
      programmes. Finally, the results confirm that the decision of the German Federal
      Medical Council (Bundesarztekammer) to exclude POC devices from accuracy checks
      against a reference method procedure in national EQA surveys was correct, at
      least at the present time.

PMID- 16955631
TI  - Measurement of vitamin D status: background, clinical use, and methodologies.
AB  - Vitamin D and its metabolites are crucial to the overall health and well-being of
      humans and animals, having important functions in calcium homeostasis and bone
      metabolism. Exposure of the skin to sunlight may provide adequate levels of
      vitamin D; however, there are numerous reports of vitamin D insufficiency or
      deficiency. 25-hydroxyvitamin D (calcidiol, 25(OH)D) is regarded as the best
      measurement of overall vitamin D status. 1,25-dihydroxyvitamin D (calcitriol,
      1,25(OH)2D) is the most biologically active vitamin D metabolite. 25(OH)D has
      higher affinity for vitamin D binding protein (VDBP) than 1,25-dihydroxyvitamin
      D; whereas, 1,25-dihydroxyvitamin D has higher affinity for the vitamin D
      receptor (VDR) than 25-hydroxyvitamin D. HPLC and immunoassays allow the
      determination of vitamin D status, as measured by 25(OH)D, and 1,25(OH)2D.
      Recently it has been shown that the vitamin D requirements have been
      underestimated and that vitamin D2 is much less potent than vitamin D3. Future
      studies will determine the amount of vitamin D3 necessary for optimal health and
      well-being.

PMID- 16955633
TI  - Recent advances in the investigation of lipoprotein metabolism using tracer
      methodology.
AB  - Dyslipidemia, the most consistent lipid disorder in subjects with obesity and
      type 2 diabetes mellitus, is associated with increased risk of coronary artery
      disease. Lipoprotein metabolism is complex and abnormal plasma concentrations can
      result from alterations in the rates of production and/or catabolism of the
      various lipoprotein particles. Our in vivo understanding of kinetic defects in
      lipoprotein metabolism in these subjects has relied on ongoing developments in
      the use of stable isotope tracers and mathematical modelling. This review deals
      with the methodological and clinical aspects of stable isotope kinetic studies.
      The design of in vivo turnover studies requires considerations related to stable
      isotope tracer administration, duration of sampling protocol, laboratory
      isolation and measurement of tracer, and interpretation of tracer data, all of
      which are critically dependent on the kinetic properties of the lipoproteins
      under investigation. Such stable isotope tracer techniques have provided a
      mechanistic insight into the understanding of lipoprotein disorders and effects
      of treatments in the metabolic syndrome. Further development in tracer
      methodologies, with practicable in-vivo protocols, are required for investigating
      cholesterol transport in plasma, tissue lipid metabolism, such as cholesterol and
      lipid transport in macrophages, liver and skeletal muscle, and the turnover of
      subpopulations of HDL particles involved in reverse cholelsterol transport.

PMID- 16955634
TI  - Novel intragenotype recombination in sapovirus.
AB  - Based on the genetic analysis, a novel, naturally occurring recombination between
      two distinct sapovirus subtypes (subtype a and subtype b) within genogroup I
      genotype 1 was identified. Breakpoint analysis of recombinant sapovirus showed
      that the recombination site was at the polymerase-capsid junction. This is the
      first report of the existence of acute gastroenteritis caused by intragenotype
      recombinant sapovirus. The results also provided evidence that the natural
      recombination occurs not only in sapovirus genogroup II but also in sapovirus
      genogroup I.

PMID- 16955635
TI  - Significance of hyperhomocysteinemia.
AB  - Moderate hyperhomocysteinemia (HHCY) is a risk factor for cardiovascular (CVD)
      and neurodegenerative diseases, osteoporotic fractures and complications during
      pregnancy. Elderly persons have a high prevalence of HHCY. Vitamin deficiency is
      by far the most common cause of HHCY. Retrospective and prospective studies
      emphasize a causal relationship between HHCY and the CVD risk. Some vitamin
      intervention trials, however, did not lower the risk of CVD. From power
      calculation one can conclude that these trials may not involve sufficient numbers
      of patients to assure statistically valid conclusions. Re-analysis of the VISP
      study (excluding renal failure and vitamin B12 status tampering factors),
      however, detected a 21% decrease in the risk of stroke. This number has been
      confirmed by results from the HOPE 2 vitamin intervention trial. Folic acid
      enrichment of grain products in the US and Canada has led to a significant
      decline of stroke mortality, since 1998 annually 12900 fewer stroke deaths in the
      US and 2800 fewer stroke deaths in Canada. Despite negative results from
      secondary prevention trials regarding the CVD risk reduction there is convincing
      evidence about the effectiveness of B-vitamin supplementation in lowering the
      stroke risk. The overall decline in stroke risk calculated in meta-analysis from
      prospective studies and found in intervention trials is around 20%. Additionally,
      HHCY was recently linked to the occurrence and severity of chronic heart failure.
      HHCY is also a risk factor for osteoporotic fractures and vitamin treatment
      lowered the fracture risk significantly. Furthermore, there is a correlation
      between HHCY and cognitive disorders or Alzheimer's disease. HHCY is a predictive
      parameter for the decline in cognitive function. Hypomethylation is among the
      central mechanisms through which HHCY acts cytotoxically. HHCY and low folate are
      causal factors for pregnancy complications. In addition to the recommended folate
      supplementation, vitamin B12 supplementation could further decrease pregnancy
      complications. Determination of homocysteine plasma concentration should be part
      of the individual risk profile, especially for elderly subjects who are at risk
      for CVD, neurodegenerative diseases or osteoporotic fractures.

PMID- 16955636
TI  - Multiparametric sensor-chip based technology for monitoring metabolic activity: A
      proof-of-principle study with live tissue.
AB  - The recent development of an electronic test system based on silicon sensor-chips
      allows the continuous parallel recording of relative changes in extracellular
      acidification, oxygen consumption and electric impedance in living cells. The
      objective of this proof-of-principle study therefore, was to clarify whether this
      system can also be applied to live tissue slices thus providing a device for an
      ultimately envisioned chemosensitivity testing apparatus for individualized
      treatment schemes in cancer therapy. A prototype of the testing apparatus
      equipped with six individual measuring devices has been used to simultaneously
      analyze changes in extracellular acidification, oxygen consumption and electronic
      impedance in live liver tissue and compared to data obtained from a tumor cell
      line. In contrast to tumor cells, tissue slices showed low rates of extracellular
      acidification but high rates of oxygen consumption. Monitoring of electrical
      impedance values, reflecting cellular morphology, revealed that the compact cell
      structure of the tissue slices was able to function as electric insulator and
      actively change the impedance values of the system. Exposure of tumor cells to 1
      microM cytochalasin B, a fungal metabolite known to interact with the
      cytoskeleton and influence glucose metabolism, resulted in the rapid decline of
      extracellular acidification, increased oxygen consumption rates and increased
      values in capacitance. In tissue slices upon addition of 1 microM cytochalasin B,
      a decline of both extracellular acidification and electrical impedance was
      observed within 1 h. Determination of ATP content in the tissue slices revealed
      that decreasing ATP content paralleled diminishing oxygen consumption. This new
      technique offers the possibility of generating metabolic profiles for cells and
      tissues by studying oxygen consumption, extracellular acidification and
      electrical impedance.

PMID- 16955637
TI  - Surveyor nuclease-based genotyping of SNPs.
AB  - Surveyor nuclease, a single-strand-specific endonuclease that cleaves DNA at the
      3' side of a base-mismatch site in both DNA strands, can be used for genotyping
      of SNPs by preparing two different types of a heteroduplex: one from mutant DNA
      fragments and the other from a mixture of wild-type and mutant fragments. We show
      an example of this technique and propose that it can be used with some advantages
      instead of RFLP analysis.

PMID- 16955638
TI  - Prognostic value of phospholipase A2 group II, C-reactive protein and Simplified
      Acute Physiological Score II in intensive care patients.
AB  - We investigated the prognostic value of group II phospholipase A2 (PLA2-II) and C
      reactive protein (CRP) in patients of the intensive care unit (ICU) who developed
      severe inflammatory reaction. In addition, the biochemical markers were
      correlated with the Simplified Acute Physiological Score II (SAPS II). Our study
      comprised 40 patients with multiple injuries and 35 patients with sepsis admitted
      to the ICU, and assessed during a follow-up of as long as 28 days. There were 18
      survivors and 17 non-survivors in the sepsis group, and 22 survivors and 18
      nonsurvivors in the group of patients with multiple injuries. In the group of
      patients with multiple injuries, the intensity of host inflammatory response
      showed clearly distinct PLA2-II and CRP profiles: the overall levels of PLA2-II
      and CRP were significantly higher in non-survivors than in survivors. PLA2-II and
      CRP do not discriminate nonsurvivors from survivors with sepsis. ROC (receiver
      operating characteristic curve) analysis and the area under the curve (AUC)
      showed the best classification of polytrauma patients with SAPS II and PLA2-II.
      In the group of patients with sepsis, only SAPS II appeared to be the most
      helpful predictive measure regarding patient outcome.

PMID- 16955639
TI  - Heparin plasma sampling as an alternative to EDTA for BNP determination on the
      Access-Beckman Coulter--effect of storage at -20 degrees C.
AB  - To determine BNP, EDTA plasma is the only suitable specimen recommended by the
      manufacturer. Since many laboratories, especially in Europe, use heparin plasma
      rather than EDTA plasma for many or most of their clinical assays and in
      particular for determination of cardiac markers (cTnI, myoglobin), it appeared
      critical to evaluate the use of heparin plasma samples, in comparison to EDTA
      plasma, for BNP determination on a automated immunochemiluminescent analyzer. The
      aim of this study was first, to evaluate the use of heparin plasma samples for
      Biosite BNP testing on the Beckman Coulter Access Immunoassay System (n=88) and
      second, to evaluate the effect of storage at -20 degrees C, without protease
      inhibitors, on the Biosite BNP assay. We obtained acceptable imprecision results
      with CVs ranging from 1.7 to 11.7% regardless of the anticoagulant used. The
      linearity of EDTA samples was good and comparable to the results observed with
      heparin plasma. The concentration of BNP was categorized according to the
      classification of the New York Heart Association (NYHA). With EDTA fresh samples
      as reference anticoagulant, 90% vs. 89% of subjects were classified as
      "concordant" with heparin fresh vs heparin frozen plasma samples, respectively.
      After storage at -20 degrees C, only 86% of the values of EDTA frozen were
      concordant with values of EDTA fresh. No subject varied by two NYHA classes.
      Heparin plasma is an attractive alternative to the established EDTA samples which
      can be used for BNP determination. This flexibility allows the simultaneous
      determination of CK, CK-MB, cTnI and BNP on a single heparin specimen, which
      facilitates blood collection for clinicians and nursing staff in an emergency
      unit. In addition, our results suggest that BNP could be stored at -20 degrees C
      for at least one month in order to perform retrospective studies.

PMID- 16955640
TI  - [Impacts and impact mechanisms of "dioxins" in humans and animals].
AB  - "Dioxins" are used to specify polychlorinated dibenzo-p-dioxins (PCDD), dibenzo
      furanes (F) and dioxin-like polychlorinated biphenyls (PCB's). Many of the
      congeners proved to be highly toxic; 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD)
      is the most toxic congener, and probably the most toxic compound ever synthesized
      by man (the natural occurance of this substance is very low). The total
      concentration/-toxicity of a mixture of congeners (WHO-PCDD/F-TEQ, or including
      the PCB's WHO-PCDD/F-PCB-PCB-TEQ) is calculated by addition of the individual
      concentrations multiplied by respective toxicity equivalence factors TEF; the
      most toxic congener TCDD is defined as 1. The tolerable weekly intake TWI set by
      the European Commission is 14pg WHO-PCDD/F-TEQ/kg bw. The "body burden" of adults
      in industrial countries is about 2-6 ng WHO-PCDD/F-TEQ/kg bw., or about double
      this value if PCB's are also considered. There is a very broad range of toxic
      effects of "dioxins". Many of the congeners can induce toxic responses at very
      low "body burdens". The most sensitive effects are immunosuppression,
      developmental and reproductive toxicity, as well as neurological behavioral
      effects. These effects occur at "body burdens" whih are close to background
      exposure of the human. Cancerogenic effects are induced at higher exposure
      (Seveso, industrial exposure). TCDD was considered a "complete carcinogen" by the
      IARC (Group 1). There is a broad range of carcinogenic effects, and there is no
      "hallmark" effect. Most toxic effects induced by TCDD are mediated by binding to
      the Ah-receptor (Ah-R) which binds together with a second protein, ARNT, to the
      respone elements of a number of target genes, and thus modulates gene expression.
      "Dioxins" are strong promotors, but weak initiators. The multitude of
      interactions of the Ah-R and ARNT ("receptor cross-talk") results in numerous
      molecular and cellular effects. The TCDD-Ah-R complex can also bind to the
      response element of the estrogen receptor, and thus can block the effects of es
      trogens. This explains the fact that TCDD can be an estrogen antagonist reducing
      or preventing mamma carcinoma. Other Ah-R ligands occur in vegetables (e.g.
      indoles, flavones) and will possibly be developed in the future as functional
      substances. PCB's have similar properties to TCDD if they can exist in a planar
      configuration (dioxin-like PCB's). The non-dioxin-like PCB's always occur
      together with "dioxins"; their toxixty cannot be adequately determined although
      they occur in high concenrations. The consumption of food contaminated with
      "dioxins" need not directly lead to a toxic effect. Due to the continous
      cumulation of "dioxins" repeated ingestion of contaminated food could result in
      an increase of the "body burden" and thus chronic toxicity. This shows that the
      exposure of the human to dioxins should be minimized wherever possible.

PMID- 16955641
TI  - [Dioxins: risk management by agriculture and feed industry--options and limits].
AB  - Dioxins represent a group of undesired substances that may contaminate
      feedstuffs. Due to their persistency in the environment it can be expected that
      feed contamination by dioxins will occur in the future, too. Therefore efforts in
      agriculture and in the feed industry have to be focussed on measures that
      minimize the dioxin contamination of feedstuffs, especially under the aspects of
      food safety. Several dioxin scandals in the past have contributed to a higher
      awareness in feed production as well as on the side of food consumers and
      administration resulting in changes of feed legislation (implementation of
      maximum levels of dioxins in feed and food). Some of the dioxin scandals enlarged
      the knowledge concerning the potential ways dioxins entering the food chain (for
      example dioxin contamination during the drying process of grass meal, recycling
      of contaminated oils, use of contaminated kaolinit a.s.o.). In difference to
      those accidents in feed producing agriculture there is a main influence of
      potential soil contamination on the dioxin contents in feedstuffs (like
      roughage). Producing roughage (green fodder, silage, hay) on areas with grass
      land by grazing animals can result in corresponding consumption of soil that
      contaminates the green fodder. Intending a lowest feed contamination by dioxins
      implies that the soil contamination is known. Depending on the rate of soil
      contamination farmers should decide on the kind of feed production and on the
      techniques of harvesting the fodder. For example it is possible to produce maize
      (whole plant in high cut technique) without higher dioxin contents in maize
      silage, on the other hand it can not be recommended to use contaminated fields
      for growing beets or by grazing ruminants, pigs or poultry (outdoor systems). In
      general during the harvesting process technical measures have to be chosen that
      reduce/minimize the soil contamination because the dioxin concentration in the
      soil of exposed areas is much more higher than the dioxin concentration within
      the feedstuffs. The high costs of dioxin analyses limit an implementation of a
      monitoring program including samples of soil and feedstuffs of each feed
      producing unit or individual farms. Therefore it is necessary to focus the
      monitoring efforts on areas and samples that let expect a higher risk of dioxin
      contamination. New screening tests should be developed and implemented that allow
      a higher frequency and density of control measures concerning dioxin. In the case
      of suspicious findings only those samples could be analysed by the classic
      chemical procedure (time consuming, high costs). Especially in cases of food
      contamination (for example detected in monitoring programs of the food industry)
      it is necessary to find out the way and cause, not neglecting the potential role
      of the contaminated soil. Last but not least it is recommended to inform the
      public continuously about levels of dioxins that are actually found in food as
      well as in feed (and soils), especially on behalf of the consumers confidence in
      food and feed control and its related administration. Continuous information will
      increase the consumers understanding that there is (and will be for further
      years) a background contamination of feed and food in general (that decreased
      markedly in the last decades), and that cases of detected higher dioxin levels
      are exceptional findings that result immediately in efforts of the food and feed
      industry to obstruct the way that enabled an entering to the food chain.

PMID- 16955642
TI  - [Origin, structure and distribution of dioxins].
AB  - Polychlorinated dibenzo-para-dioxins (PCDD) and polychlorinated dibenzofurans
      (PCDF) are generated as unintentional by-products in a number of thermal and
      chemical-industrial processes. Biogenic formation through dimerization of
      chlorinated precursors, such as chlorophenols, is know but does not play a major
      role in national dioxin release inventories and in most cases is not quantified.
      PCDD/PCDF are semi-volatile substances and undergo long-range transport; they are
      persistent and accumulate in the environment and organismus; and they are toxic.
      They have become a global environmetnal problem. At the international level this
      issue is addressed by the Stockholm Convention on Persistent Organic Pollutants,
      a legally binding instrument to eliminate PCDD/PCDF through step-wise
      implementation of reduction measures. Within the Stockholm Convention, Parties
      have to develop national or regional dioxin inventories. First results show that
      in most industrialized countries, incineration of municipal solid waste does no
      longer represent the largest dioxin source; instead, certain processes in the
      metallurgical industry have become largest emitters. In developing countries, the
      situation is very different: open burning processes such as forest and grassland
      fires, burning of agricultural residues either before or after harvest as well as
      fires in waste dumps or the private fires to dispose of municipal waste represent
      the largest dioxin sources. First steps for a global environmental monitoring
      program under the Stockholm Convention have been initiated.

PMID- 16955643
TI  - [Chemical and effect-related analysis of dioxins and dioxinlike PCB's].
AB  - Dioxins and dioxinlike PCBs are high toxic and persistent compounds. They
      accumulate in the feed and food chain. Because of their occurrence in a very low
      concentration range, the established requirements for analytical methods are
      restrictive. Commission Directive 2002/69/EC of 26 July 2002 lays down sampling
      methods and methods of analysis for the official control of dioxins and
      dioxinlike PCBs in foodstuff. Confirmatory methods are high resolution gas
      chromatography/high resolution mass spectrometry (HRGC/HRMS). Screening methods
      could be used to select samples with significant levels of dioxins. Bioassay--for
      example the EROD-Bioassay--can be used as a screening method.

PMID- 16955644
TI  - [Examples of accidental and continuous exposures. ].

PMID- 16955645
TI  - [Administrative risk management--possibilities and limits].

PMID- 16955646
TI  - Virtual occlusion--undreamed-of possibilities.

PMID- 16955647
TI  - Evaluation for the fully automatic inlay reconstruction by means of the
      biogeneric tooth model.
AB  - Length measurements and descriptive characterizations were previously the sole
      reference points for describing the morphology of the occlusal surface. For
      computerized methods in dentistry, this is not sufficient for producing a data
      record. So far, the literature has reported no solutions. With the aid of a tooth
      library containing three-dimensionally measured occlusal surfaces free of caries
      and abrasion, a mathematical model was produced to describe a certain type of
      tooth by reference to a few parameters, taking account of functional and
      biologically relevant structures. This biogeneric tooth model was tested on 27
      different inlay situations. The results show that fully automatic reconstruction
      was possible in all cases. The deviations of the reconstructions from the
      original tooth surface were on average around 150 microm. Furthermore, the
      influence of different parameters on the mathematical model was examined. Here,
      combinations that guarantee the best possible reconstruction for many situations
      could be found. The visual evaluation and the metric comparison of the
      reconstructions among one another illustrate the great flexibility of the
      biogeneric tooth model. With the aid of the biogeneric tooth model, there is the
      possibility of reconstructing the occlusal surfaces of dental restorations by
      CAD/CAM processes fully automatically, taking account of morphological and
      functional criteria. Further studies are needed to show to what extent the
      inclusion of degree of abrasion, antagonist and adjacent teeth delivers the
      desired results in the whole spectrum of clinical cases.

PMID- 16955648
TI  - Concept and development of a computerized positioning of prosthetic teeth for
      complete dentures.
AB  - To date, CAD/CAM technology has made no noteworthy inroads into removable
      dentures. We want to present a new area of application for this in our study.
      Models of the maxilla and edentulous mandible were 3D scanned. The software
      detects and automatically reconstructs the reference structures that are
      anatomically important for the set-up of artificial teeth, such as the alveolar
      ridge centerlines and the interalveolar relations between the alveolar ridges. In
      a further step, the occlusal plane is semiautomatically defined and the front
      dental arch is designed. After these design features have been determined,
      artificial teeth are selected from a database and set up automatically. The
      dental technician can assess the esthetics and function of the suggested dental
      set-up on the computer screen and make slight corrections if necessary.
      Summarizing: The interplay of hardware and software components within on
      integrated solution including conversion of the "virtual" into a real positioning
      of prosthetic teeth is presented.

PMID- 16955649
TI  - Optimization of the static occlusion by "occlusal surface settling" in the Cerec
      3D software.
AB  - The adjustment of the static occlusion can be automated in computer-based
      systems. The Cerec 3D software makes it possible to take preformed occlusal
      surfaces from a database and adapt them to the antagonist. In this adaptation
      (settling), the CAD occlusal surface "settles" as whole or each cusp individually
      into the occlusal surface of the antagonist until stable occlusion is reached.
      Two occlusal surface shapes were compared: Vita Physiodens and Lee Culp. An index
      was formed from the number, quality, and position of the occlusal contacts for 35
      model cases (25 molars, 10 premolars). With regard to the settling of the total
      occlusal surfaces, there were no differences between the two occlusal surface
      shapes. In "cusp settling" of the molars, Vita Physiodens performed significantly
      better. In the comparison of the 1st with the 3rd settling process, significant
      improvements occurred the 3rd time in many cases when settling individual cusps,
      but in clearly fewer cases in the settling process of the total occlusal surface.
      The Lee Culp tooth occlusion improved especially after the 3rd settling process
      of individual cusps. It is therefore expedient to combine both settling versions
      with one another.

PMID- 16955651
TI  - Clinical reproducibility of GEDAS--"Greifswald Digital Analyzing System" for
      displaying occlusal contact patterns.
AB  - The clinical display of the occlusal contact points is an essential part of the
      quality control of restorative work. Normally, articulating paper of different
      colors, occlusion foil or special waxes are used for this. A possible digital
      method has to date been to display the contact points and their distribution
      using a pressure sensor foil (T-Scan system). Occlusion bites in a silicone
      material are also possible alternatives. The Greifswald Digital Analyzing System
      (GEDAS) displays the strength, extent and localization of static contacts in
      intercuspation (IP) based on digitized silicone registrations. In 10 completely
      dentulous test persons (age 23 to 29 years), with 3 different examiners as well
      as 2 examination times spaced 14 days apart, the intraindividual reproducibility
      of the contact relations resulted in kappa values of 0.92, 0.96 and 0.99, and the
      interindividual reproducibility was between 0.90 and 1.00. Different versions of
      the GEDAS software are presented, including explanation and discussion of the
      possibilities of use.

PMID- 16955650
TI  - Comparison of the contact surface pattern between virtual and milled Cerec 3D
      full-ceramic crowns.
AB  - PURPOSE: The objective of this study was to compare resulting contact point
      patterns in the context of crown production with the Cerec 3D system. The contact
      surface patterns of full-ceramic crowns milled with the Cerec 3D system were
      examined for agreement with the corresponding virtually produced crowns.
      MATERIALS AND METHODS: The agreement was determined with regard to the parameters
      number, size, position, and shape. Twenty-eight models were mounted centrally in
      a mechanical articulator. In these model cases, at least one second premolar and
      one first molar in the maxilla and mandible had to be prepared for crown
      production (preparation). A total of 50 teeth was prepared. Crowns were then
      designed with the aid of the Cerec 3D system. The crown designs were milled and
      integrated in the model. Silicone bite registrations, the contact point patterns
      of which were compared with the virtually designed crowns, were produced in
      static occlusion in the region of the crowns. Different evaluation methods were
      used for the comparison. RESULTS: There was an agreement of 78% with regard to
      number, 76% in terms of localization, 65% regarding size, and 65% in terms of
      shape. CONCLUSION: It was thus confirmed that very good, highly reproducible
      results can be achieved with the Cerec 3D system.

PMID- 16955652
TI  - Analysis of the variability of occlusal function patterns in masticatory movement
      -use of the GEMAS software.
AB  - Individual masticatory patterns are similar to chaotic tangles of tortuous paths
      and are characterized by variability. The analysis of such masticatory patterns
      is therefore difficult. The new GEMAS software--Greifswald Movement Analyzing
      System--with which the variability of the masticatory function can be examined,
      is presented. Intersecting planes are placed through the orbit of the chewing
      cycles with which it is possible to wonder from the intercuspal position up to
      the maximum mouth-opening position of the masticatory pattern. The opening and
      closing points are displayed in different colors. Zones where masticatory paths
      converge or diverge can be determined, including the fan or funnel-shaped
      entering and exiting movements close to the centric position and the extent of
      their spread. A special diagram visualizes the rhythmic sequence of entering and
      subsequent exiting movement. The relation between restricted variability or
      monotony and forms of disease of the masticatory system is indicated by reference
      to case examples. The more monotonous or stereotyped the chewing cycles are, the
      higher is the risk of permanent wear of anatomical structures. Attention should
      therefore also be paid to variability in the individual occlusal surface design
      of dental restorations.

PMID- 16955653
TI  - Assessment of ceramic restorations according to the Cerec method.

PMID- 16955654
TI  - Prevention and women's reproductive health: a matter of concern.

PMID- 16955655
TI  - The clubhouse as an empowering setting.
AB  - Attention to psychosocial rehabilitation (PSR) practice has expanded in recent
      years. However, social work research studies on PSR are not numerous. This study
      focuses on operational characteristics of clubhouses, a major PSR program model,
      and the organizational attributes (including resource levels) that predict the
      extent to which the clubhouse constitutes an empowering setting. The authors
      present data from a statewide sample of 30 clubhouses, annually serving nearly
      4,000 consumers (adults with serious mental illnesses), based on interviews of
      clubhouse directors, on-site observations, and government information sources.
      Results indicate that users were predominantly male, white, and middle age; about
      one-third had a major functional disability. There were wide variations in member
      characteristics as well as in resource levels. In terms of empowerment, this
      sample of clubs averaged rather low levels of member involvement in governance
      and operations but seemed to provide members with opportunities and assistance in
      making their own decisions. The empowerment variables had different predictors,
      including client characteristics, urban-related characteristics, staffing, and
      resource levels. Implications for social work practice in PSR settings are
      discussed.

PMID- 16955656
TI  - Significance of gender and age in African American children's response to
      parental victimization.
AB  - This study examined gender and age differences in children's psychological
      response to parental victimization in a convenience sample of African American
      children. Thirty youths, ages six to 12, whose parents had been a victim of
      community violence (that is, gunshot or stabbing), and a control group of 30
      children matched on variables of race, age, gender, and neighborhood served as
      the sample for this study. Parents completed a demographics sheet and the Child
      Behavior Checklist. Data were collected within six weeks of parental
      victimization. No significant difference was found in male and female youths'
      internalizing and externalizing behavior at ages six to eight. However, beginning
      at age nine there was a significant difference in behavior. Youths exposed to
      parental victimization internalized and externalized to a greater degree than
      those children who were not exposed. Males externalized more than females, and
      females internalized more than males. Thus, the perceived trauma response may
      vary as a function of the child's gender and developmental level or age. These
      findings suggest that gender-specific response related to trauma exposure may
      begin as early as age nine.

PMID- 16955657
TI  - End-of-Life decision making for nursing home residents with dementia: a survey of
      nursing home social services staff.
AB  - The purpose of this survey was to describe nursing home social services staff
      roles and perceptions related to end-of-life medical decision making for nursing
      home residents in endstage dementia. Using a self-designed questionnaire, 138
      nursing home social services staff from across New York State answered questions
      about advance directives, medical interventions, and comfort levels with
      withholding and withdrawing of treatment. Results showed a high degree of
      involvement in advance directive discussions, problems in the implementation of
      advance directives, and wide variation in comfort levels with treatment issues.
      Results of this study indicate areas of need for further research and training of
      nursing home social services staff.

PMID- 16955658
TI  - A survey of the health, sleep, and development of children adopted from China.
AB  - The health, development, and sleeping patterns of 240 children adopted from China
      were examined using a survey research approach. Eighty percent of the children
      were 18 months of age or younger when adopted, and 98 percent of the children
      were girls. Sixty-two percent of the children were reported to have been
      developmentally delayed at the time of adoption; of this number, 91 percent were
      reported to have had delays in motor development. Of the families, 52 percent
      reported that children experienced sleep problems, but only 9 percent of the
      total sample experienced significant sleep difficulties. Implications for social
      workers are also discussed.

PMID- 16955659
TI  - Fostering resilience in siblings of youths with a chronic health condition: a
      review of the literature.
AB  - An accumulating body of literature points to the potential for successful
      outcomes among families who have a child with a chronic health condition.
      Resilience research has catalyzed a reconceptualization of the experience of such
      families from a deficit, pathological perspective to a growth-enhancing
      opportunity. However, scant data available about the specific risk and protective
      mechanisms influencing the psychosocial outcomes of well siblings in these
      families are lacking. This article draws on the literature addressing resilience
      in youths experiencing adversity to inform social workers about how to better
      promote positive outcomes among well siblings. Implications for future research
      and suggestions for social work practice to target the unique needs of well
      siblings are discussed.

PMID- 16955660
TI  - Do not forget about your volunteers: a qualitative analysis of factors
      influencing volunteer turnover.

PMID- 16955661
TI  - Addressing sexual issues in individuals with chronic health conditions.

PMID- 16955662
TI  - Social work ethics audits in health care settings: a case study.

PMID- 16955663
TI  - Medicaid coverage of newer psychotropic medication.

PMID- 16955664
TI  - Social work in the Department of Veterans Affairs: lessons learned.

PMID- 16955665
TI  - Capsaicin, transient receptor potential (TRP) protein subfamilies and the
      particular relationship between capsaicin receptors and small primary sensory
      neurons.
AB  - A number of subfamilies of the capsaicin receptor, collectively called TRP, have
      been reported since the discovery of vanilloid receptor 1 (VR1). The term 'TRP'
      is derived from 'transient receptor potential', which means the transient and
      rapid defect of reaction following long stimulation with light in the
      photoreceptor cells of mutant Drosophila. The common features of TRP family
      members are the centrally situated six transmembrane domain, in which an ion
      channel is located, three to four ankirin repeats at the N-terminus and a TRP
      domain comprising 25 amino acids at the C-terminus. The TRP family members are
      present in animals, including invertebrates and vertebrates, and in the cells in
      various tissues in individual animals. During evolution, the original TRP seems
      to have acquired a wide variety of functions related to sensing the inner or
      outer environment (e.g. to sensing light (Drosophila), osmolarity, protons,
      temperature, ligands and mechanical force). In mammals, the TRPV subfamily is
      exclusively expressed in small- to medium-sized primary sensory neurons that also
      co-express some chemical markers (i.e. isolectin B4 (IB4), fluoride-resistant
      acid phosphatase (FRAP), the P2X3 purinoceptor (a receptor provoked by ATP
      induced nociception) and Ret, a glial cell line-derived neurotrophic factor
      receptor). There is a paradox in that regardless of the marked or complete loss
      of noxious, small sensory neurons (polymodal nociceptors) in mice treated with
      capsaicin during the neonatal period, as well as in VR1 (TRPV1)-deficient knock
      out mice, the responses to noxious heat are normal. Regarding the paradox in mice
      treated with capsaicin as neonates, our explanation is that although capsaicin
      probably reduces the number of a subgroup of small neurons (IB4-, VR1+), the
      remaining IB4+ (VR1-) neurons can sense noxious heat normally. One working
      hypothesis is that mice lacking TRPV1/2 can sense noxious heat under normal
      conditions, presumably via another still unknown pathway, and TRPV1 has been
      suggested to be involved in noxious heat transduction under pathological
      conditions, such as inflammation and tissue injury. Further studies will be
      required to clarify these complexities. Mice treated with capsaicin as neonates
      would provide a model to investigate the above paradoxes, as would TRPV1-knock
      out mice, although different mechanisms may be operating in the two models.

PMID- 16955666
TI  - Expression dynamics and functional implications of DNA topoisomerase II beta in
      the brain.
AB  - Mammalian DNA topoisomerase II beta is a type II DNA topoisomerase that catalyses
      topological transformations of genomic DNA by the transport of one DNA double
      helix through another. The II beta enzyme is highly expressed in cells that have
      undergone the final cell division and committed to differentiate into neuronal
      cells. The II beta enzyme in the differentiating neuronal cells is located in the
      nucleoplasm and is actively engaged in its catalytic reaction in vivo. When
      enzyme action is interfered with a specific inhibitor in vitro, transcriptional
      induction of a subset of genes fails to occur during neuronal differentiation.
      Detailed analyses of developing rat cerebellum and the cerebrum of mice with
      disrupted II beta genes have revealed that DNA topoisomerase II beta is necessary
      for the developmentally regulated expression of certain genes in cells committed
      to a neuronal fate after the final division. Herein, we review a dynamic aspect
      of DNA topoisomerase II beta in the brain with special emphasis on developing
      cerebellar neurons.

PMID- 16955667
TI  - Cyclo-oxygenase-2-immunoreactive neurons in the lumbar dorsal horn in a chicken
      acute inflammation model.
AB  - Acute and chronic peripheral inflammation is known to induce the expression of
      cyclo-oxygenase (COX)-2 in spinal cord neurons and increase the synthesis and
      release of prostaglandins (PG). Although these PG are presumed to cause
      inflammatory pain or hyperalgesia, the relationship between PG-producing cells in
      the dorsal horn and substance P (SP)-containing, pain-transmittimg nerve fibers
      remains unknown. In the present study we investigated immunohistochemically
      changes in the number of COX-2-containing neurons using the avidin-biotinylated
      peroxidase complex method in dorsal horn superficial laminae in chicken
      lumbosacral enlargement (L4, L5) under inflammatory conditions induced by
      unilateral intraplantar injection of complete Freund's adjuvant. After 12-24 h, a
      significant increase in the number of small COX-2-containing neurons was observed
      in lamina II on the injected side compared with the contralateral side.
      Furthermore, using fluorescent double-labeling for COX-2 and SP, an increase in
      the number of small COX-2-containing neurons in contact with SP-containing
      elements was observed ipsilaterally (1.4-1.6-fold compared with the contralateral
      side) in lamina II. Fluorescence triple-labeling of COX-2, SP and calcitonin gene
      related peptide (CGRP) confirmed that the majority of these SP-containing
      elements coexisted with CGRP, indicating that these elements originated from
      primary afferent neurons. Using electron microscopy, two types of SP-containing
      axon terminals were found to form synapses with COX-2-containing neurons in
      lamina II. These results indicate that the number of COX-2-containing neurons
      increases concomitantly with an increase in the number of contacts of these
      neurons with SP-containing primary afferent fibers and suggest that this
      phenomenon is associated with PG production and the persistence of inflammatory
      pain.

PMID- 16955668
TI  - Total occipitalization of the atlas.
AB  - Occipitalization of the atlas is an important congenital malformation of the
      craniovertebral region because of the proximity to the spinomedullary region. In
      a sample of 109 human adult skulls of Asian origin examined for evidence of
      atlanto-occipital fusion, only one specimen exhibited this type of anomaly, in
      which the atlas was totally synostosed with the occipital bone with multiple bony
      defects. The embryological basis of this congenital abnormality is discussed.

PMID- 16955669
TI  - Systemic labeling and visualization of dental sensory nerves by the novel
      fluorescent marker AM1-43.
AB  - Systemic labeling of sensory nerves was performed by injecting a small amount of
      the styryl dye AM1-43 subcutaneously to the back skin of 4-week-old mice in order
      to determine its ability to stain sensory nerves. One or 3 days later, dental
      tissues were fixed and cryosectioned. Molars showed bright nerve fibers in the
      periodontal ligament and pulp. Nerve fibers in dentinal tubules approximately 100
      microm from the pulp were also labeled. In the incisor, there were only few
      labelings in the pulp, although free nerve endings and Ruffini-type
      mechanosensors in the periodontal ligament on the lingual side were brightly
      labeled. The AM1-43-positive fibers were also labeled by anti-PGP9.5. AM1-43 is
      an excellent marker for sensory nerves and it may be useful for further
      investigations of dental innervation and in exploring new analgesics for tooth
      pain.

PMID- 16955670
TI  - Intramuscular nerve distribution pattern of the oblique and transverse heads of
      the adductor hallucis muscles in the human foot.
AB  - To understand which layer of the intrinsic muscles of the foot the adductor
      hallucis muscle belongs to, it is essential to investigate the innervation
      patterns of this muscle. In the present study, we examined the innervation
      patterns of the adductor hallucis muscles in 17 feet of 15 Japanese cadavers. We
      investigated the intramuscular nerve supplies of the adductor hallucis muscles in
      six feet and performed nerve fiber analysis in three feet. The results indicate
      that: (i) the oblique head of the adductor hallucis muscle is divided into three
      compartments (i.e. lateral, dorsal and medial parts) or two compartments (i.e.
      dorsal and medial parts) based on its intramuscular nerve supplies, but we could
      not classify the transverse head into any parts; (ii) the communicating twig
      between the lateral and medial plantar nerves penetrated the oblique head of the
      adductor hallucis muscle in 13 of 17 feet (76.5%); (iii) the penetrating twig
      entered between the lateral and dorsal parts of the oblique head, passed between
      the lateral and medial parts of this muscle and then connected with the medial
      plantar nerve; and (iv) the majority of the nerve fibers of the penetrating twig
      derived from the lateral plantar nerve. The present study demonstrated that only
      the lateral part of the oblique head of the adductor hallucis muscle had a unique
      innervating pattern different from other parts of this muscle, suggesting that
      the lateral part of the oblique head has a different origin from other parts of
      this muscle.

PMID- 16955671
TI  - An anomalous muscle linking superior and inferior rectus muscles in the orbit.
AB  - Dissections of the bilateral orbits in a 45-year-old female cadaver, who had no
      ocular movement disorders in her lifetime, revealed anomalous muscles linking the
      superior and inferior rectus muscles. The muscles, situated between the optic
      nerve and the lateral rectus muscle, originated from the annulus of Zinn and
      branched off two heads; one inserted into the medial inferior side of the
      superior rectus muscle and the other inserted into the central superior side of
      the inferior rectus muscle. Each insertion was located on a distal site of the
      myoneural junction of each rectus muscle. Histological investigations showed that
      the muscles had a striated muscle structure. No definite nerve insertion was
      observed in the muscles. Although this type of anomalous muscle has been reported
      in a few Caucasian cases, the present study is the first report in an Asian
      person. Anomalous orbital structures, which are a rare cause of strabismus, are
      important in the differential diagnosis of intra-orbital space-occupying lesions,
      rather than the differential diagnosis of strabismus.

PMID- 16955672
TI  - The Glasgow heritage.

PMID- 16955673
TI  - British influence on Maltese dentistry.

PMID- 16955674
TI  - Thomas Bell.

PMID- 16955675
TI  - Dentistry for pauper and other poor children in the late 19th and early 20th
      centuries.

PMID- 16955676
TI  - Frank Harrison (1859-1912).

PMID- 16955677
TI  - Professor Dr.Med. Dr.Med.Dent Curt Gerhard Lorber.

PMID- 16955678
TI  - Dental burs at the design exchange in Toronto, Canada.

PMID- 16955679
TI  - Targeting infectious diseases in the genomics era.

PMID- 16955680
TI  - Vaccines against human papilloma viruses.

PMID- 16955681
TI  - Masked oral prodrugs of toll-like receptor 7 agonists: a new approach for the
      treatment of infectious disease.
AB  - Toll-like receptor (TLR)7 is a pattern-recognition receptor that activates the
      innate immune response. Stimulation of TLR7 induces type I interferons, pro
      inflammatory cytokines, the upregulation of co-stimulatory molecules and leads to
      the development of an adaptive immune response. Small-molecule TLR7 agonists with
      broad-spectrum antiviral activities in animal models have been identified. Such
      compounds have been examined clinically for a number of different infectious
      disease indications, leading to marketing approval of one of these agents,
      imiquimod, for the topical treatment of external genital and perianal
      papillomavirus infections. In contrast with topical and intravenous routes of
      administration, compounds delivered orally have exhibited poor tolerability at
      desired doses, with substantial adverse events associated with gastrointestinal
      toxicity. However, dosing with masked oral prodrugs of TLR7 agonists, such as ANA
      975, limits the adverse events associated with the activation of responsive
      gastrointestinal immune tissue. As a consequence, the treatment of systemic
      diseases, such as chronic hepatitis C, can now be explored with orally
      administered TLR7 agonists.

PMID- 16955682
TI  - Transmitted multidrug resistant HIV-1: new and investigational therapeutic
      approaches.
AB  - The increasing prevalence of transmitted drug-resistant HIV-1 has highlighted the
      challenging issue of the optimal management of antiretroviral-naive, newly
      infected patients with multidrug-resistant HIV-1. This review discusses current
      trends in the evolution and transmission of HIV-1 with reduced susceptibility to
      multiple antiretroviral agents. In most cases, clinical strategies for the
      management of such patients with stable virological and immunological parameters
      involve deferment of therapy until clinically indicated. When a decision is made
      to initiate therapy, the process of selecting a regimen should consider baseline
      viral genotype and phenotype results, as well as the inclusion of novel agents
      with diverse mechanisms of action, in order to achieve a more complete
      suppression of viral replication. A summary of established and investigational
      antiretroviral agents is presented in this review, together with novel
      therapeutic approaches to decrease the burden of viral replication and maintain
      immunological status in cases of transmitted multidrug-resistant HIV-1 infection.

PMID- 16955683
TI  - Small-molecule HIV-1 gp120 inhibitors to prevent HIV-1 entry: an emerging
      opportunity for drug development.
AB  - The HIV-1 gp120 envelope protein is an essential component in the multi-tiered
      viral entry process. Despite the overall genetic heterogeneity of the gp120
      glycoprotein, the conserved CD4 binding site provides an attractive antiviral
      target. Recently, increased efforts aimed at the development of inhibitors of
      gp120 have been reported. This review focuses primarily on small-molecule gp120
      inhibitors and discusses key characteristics of compounds that appear to fall
      within this class. The preclinical profiles of compounds that prevent gp120 from
      assuming a conformation favorable for CD4 binding are described in this review.
      In addition, inhibitors possessing some common structural features, including at
      least one compound that exhibits sub-nanomolar potency in a cell fusion assay are
      discussed. A series of compounds that were designed to enhance immune responses
      to virus via alteration of the gp120 conformation after targeting the CD4 binding
      pocket are also described. The efficacy of gp120 inhibitors as a microbicide to
      prevent sexual HIV transmission in the rhesus macaque model is discussed. Results
      suggest that this class of compounds may have value if included in a microbicide
      cocktail with inhibitors of alternate mechanisms. Importantly, preliminary
      results from clinical studies of orally administered BMS-488043 demonstrate that
      antiviral efficacy can be achieved in humans with a CD4-attachment inhibitor that
      targets gp120.

PMID- 16955684
TI  - Hepatitis C virus entry: an intriguing challenge for drug discovery.
AB  - The entry of hepatitis C virus (HCV) into host cells is an obligatory step in
      virus replication that presents a multi-faceted opportunity for drug discovery.
      However, the current understanding of HCV entry is rudimentary at best, with
      insights to date obtained by examining the fusion of pseudoparticles that express
      the HCV surface glycoproteins E1 and E2. The absence of an infectious virus
      replication system capable of replicating through a full virus life-cycle has
      hampered progress in determining the events involved in viral entry, resulting in
      considerable ambiguity surrounding the process. The recent development of an
      infectious HCV virus replication system provides a method with which to examine
      HCV entry in detail in a setting that promises greater authenticity and with the
      potential to increase understanding of this process. Weak inhibitors of the
      interactions between the HCV glycoproteins and potential host cell receptors have
      been identified, but their mechanism of action, in the context of virus
      infectivity, is not understood, and these inhibitors remain to be validated with
      infectious virus in cell culture. The advent of an infectious virus replication
      system holds considerable promise for developing a detailed understanding of HCV
      entry, but while mechanistic insights developed with other viruses may provide
      useful paradigms for experimental design, it is likely that HCV entry will be
      characterized by several unique biochemical events. Developing a deeper
      understanding of HCV entry will clearly take some time given the complexity of
      the process and the current state of affairs. Nevertheless, interfering with HCV
      entry holds promise for drug design and discovery as the mechanistic insights
      emerge and coalesce into a coherent biochemical description of the process.

PMID- 16955685
TI  - Serogroup B meningococcal vaccines.
AB  - Neisseria meningitidis causes severe, often fatal septicemia and meningitis.
      Polysaccharide vaccines that offer protection against infection with
      meningococcal serogroups A, C, Y and W-135 are effective in older children and
      adults, and have been widely used. New polysaccharide-conjugate vaccines against
      one or more of these serogroups are now in use or under accelerated development;
      however, a broadly protective vaccine against infection by serogroup B N
      meningitidis is not yet available. Serogroup B contributes significantly to the
      burden of meningococcal disease in many industrialized countries where both
      epidemic and endemic serogroup B infections occur. Vaccines effective against
      specific strains responsible for serogroup B epidemic disease have been
      developed, but the development of a safe serogroup B vaccine that is cross
      protective against multiple strains and is effective in infants and young
      children is a challenge. In spite of these difficulties, promising approaches
      stemming from a better understanding of meningococcal pathogenesis and of the
      genetics of serogroup B N meningitidis continue to evolve. Progress toward an
      effective serogroup B vaccine, an important addition for meningococcal disease
      prevention, is the focus of this review. The epidemiology and pathogenesis of
      meningococcal disease are detailed, along with discussion of the challenges faced
      in the development of efficacious serogroup B vaccines.

PMID- 16955686
TI  - Glycopeptides and glycodepsipeptides in clinical development: a comparative
      review of their antibacterial spectrum, pharmacokinetics and clinical efficacy.
AB  - Hemi-synthetic derivatives of glycopeptides have demonstrated bactericidal
      activity towards Gram-positive bacteria, including vancomycin-resistant strains
      (oritavancin and telavancin), and a prolonged half-life, allowing for once-daily
      (oritavancin and telavancin) or once-weekly (dalbavancin) administration. These
      compounds have proved effective for the treatment of infections caused by
      multidrug-resistant Gram-positive bacteria, including complicated skin and skin
      structure infections (oritavancin, telavancin and dalbavancin), bacteremia
      (oritavancin and dalbavancin) and nosocomial pneumonia. This review compares the
      antibacterial activity and clinical activity of three glycopeptides, oritavancin,
      telavancin and dalbavancin, and the natural lipoglycopeptide, ramoplanin, which,
      being unstable in the bloodstream, is administered orally to treat Clostridium
      difficile colitis and for digestive tract decontamination. All of these
      compounds, with the exception of oritavancin, have received Fast Track
      designation from the FDA because of their clinical efficacy.

PMID- 16955687
TI  - Drug evaluation: Albuferon-alpha--an antiviral interferon-alpha/albumin fusion
      protein.
AB  - Human Genome Sciences Inc (HGS), in collaboration with Novartis AG, is developing
      Albuferon-alpha, a long-acting injectable human interferon alpha2b fusion
      protein, for the potential treatment of hepatitis C virus (HCV) infection. By May
      2004, phase II clinical trials of Albuferon in HCV infection were underway. In
      June 2006, HGS planned to initiate phase III clinical trials in this indication
      by the end of 2006. Albuferon also has the potential to treat a broad range of
      cancers.

PMID- 16955688
TI  - Drug evaluation: bevirimat--HIV Gag protein and viral maturation inhibitor.
AB  - Panacos Pharmaceuticals Inc is developing the HIV Gag protein and viral
      maturation inhibitor bevirimat for the potential oral treatment of HIV infection.
      Phase II clinical trials are underway and phase III trials expected to commence
      in 2007.

PMID- 16955689
TI  - Drug evaluation: BAL-8557--a novel broad-spectrum triazole antifungal.
AB  - Basilea Pharmaceutica is developing BAL-8557, a water-soluble prodrug of the
      triazole BAL-4815, for the potential treatment of fungal infections. By August
      2005, a phase II study in oral candidiasis was underway. In September 2005, phase
      III trials were planned for invasive Candida and mold infections, including
      aspergillus and zygomycetes.

PMID- 16955690
TI  - ApoE gene therapy to treat hyperlipidemia and atherosclerosis.
AB  - Atherosclerosis is the leading cause of death in industrialized countries and is
      becoming an increasingly worldwide risk to health. Apolipoprotein E (ApoE) is a
      blood circulating protein with pleiotropic atheroprotective properties that has
      emerged as a strong candidate for treating hypercholesterolemia and
      cardiovascular disease. In this review, we discuss the major developments in both
      viral and non-viral vectors aimed at achieving efficient delivery and sustained
      expression of an ApoE transgene. The technological advances in engineering
      viruses include cross-packaging to generate different serotypes of recombinant
      adeno-associated virus, and the use of multiple-deleted and helper-dependent
      recombinant adenovirus vectors to minimize immune responses and to package
      genomic loci. Non-viral ApoE delivery systems, including plasmids and cell-based
      therapy are also described in this review. Finally, a radical alternative to gene
      addition that has the potential for permanent cure in many genetic diseases-
      'targeted gene editing'--is reviewed. This technology uses synthetic
      oligonucleotides to correct underlying point mutations in situ and has been
      evaluated for repairing dysfunctional APOE genes.

PMID- 16955691
TI  - Gene therapy and coronary artery bypass grafting: current perspectives.
AB  - The early success of coronary artery bypass grafting (CABG) is limited by
      disappointing long-term patency rates of autologous saphenous vein grafts.
      Because current pharmacological interventions have only limited impact on vein
      graft patency rates, there remains a clear clinical need for effective agents to
      prevent failure of vein grafts in the long term. Gene therapy in vein grafts has
      great potential as gene delivery can be achieved ex vivo at the time of cardiac
      surgery, allowing transgene expression to occur rapidly post-grafting within the
      acute phase of vein graft remodelling. A variety of therapeutic strategies have
      been tested in a range of preclinical models, although to date, these have not
      advanced to Inhuman trials, except in the setting of adjunctive angiogenesis for
      improved revascularization (phase 1). Clinical translation is warranted to
      investigate the potential of gene therapy to improve CABG patency rates in the
      long term.

PMID- 16955692
TI  - An update on angiogenic gene therapy: vascular endothelial growth factor and
      other directions.
AB  - Therapeutic angiogenesis is a promising new concept for the treatment of tissue
      ischemia and other related medical conditions or processes, such as wound
      healing. Members of the vascular endothelial growth factor (VEGF) family are
      among the most powerful modulators of vascular growth; they regulate vascular
      growth and maintenance during embryogenesis and in adults. Despite progress in
      basic research and preclinical animal studies of therapeutic angiogenesis,
      significant problems still exist in translating experimental findings into
      beneficial clinical approaches. This review summarizes these problems and
      highlights recent findings in the field of therapeutic angiogenesis using VEGF
      and other factors, with special reference to potential clinical applications.
      Also, in order to better optimize vectors, doses and treatment approaches, it is
      proposed that the analysis of new parameters is introduced. These parameters
      consist of: i) spreading throughout and reaching appropriate cells in the target
      tissue, ii) transfection efficiency, iii) expression strength, and iv) duration
      of expression. It is envisaged that this 'STED' analysis will aid the clinical
      development of gene therapy.

PMID- 16955693
TI  - Striking out at disseminated metastases: the systemic delivery of oncolytic
      viruses.
AB  - Oncolytic viruses are capable of selective replication in malignant cells and
      therefore offer levels of potency and specificity that are potentially far higher
      than conventional treatments for cancer. New developments in vector design and
      administration regimes are gradually moving toward systemic applications, with
      the ultimate aim of treating common cancer indications that present with multiple
      disseminated metastases. Nevertheless, the delivery of therapeutic quantities of
      viruses via the blood stream to target cells in humans or stringent animal models
      remains a challenging task: the relatively large size of virus particles
      restricts their penetration into tissues, and defines their biodistribution and
      clearance kinetics. In addition, multiple interactions with blood cells and serum
      proteins can impact on vector bioavailability. Finally, the immunological
      response to virus administration can vary considerably from patient to patient
      and even more so between species, making it difficult to draw accurate clinical
      predictions from model systems. Unfortunately, the extensive experience gained
      from the application of low-molecular-weight therapeutic drugs provides little
      insight into the behavior of viral therapeutics administered into the blood
      stream. In this review, the fate of virus particles following intravenous
      delivery is described, followed by an assessment of the latest approaches to
      control and improve vector delivery.

PMID- 16955694
TI  - Naturally oncolytic viruses.
AB  - Naturally oncolytic viruses are replication-competent viruses that have an innate
      ability to selectively infect and kill tumor cells. Despite being used in the
      original attempts to treat cancer with live viruses five decades ago, interest in
      naturally oncolytic viruses has lagged behind the support for engineered
      adenoviruses and herpesviruses as cancer therapeutics. Recently, however, there
      has been renewed interest in the high potency and selectivity of these naturally
      occurring agents. In this review, the mechanism of selectivity as well as the
      preclinical and clinical activity of naturally oncolytic viruses will be
      discussed.

PMID- 16955695
TI  - A demand for next-generation oncolytic adenoviruses.
AB  - Oncolytic viruses are a class of novel therapeutic agents used for the treatment
      of cancer that have the unique property of tumor-dependent self-perpetuation.
      Initial clinical trials have demonstrated that these agents are very safe and
      well tolerated. However, to date they have failed to demonstrate therapeutic
      benefit as monotherapies and as a consequence, next-generation oncolytic
      adenoviruses are now needed. This review discusses the approaches to deriving
      next-generation oncolytic adenoviruses together with potential preclinical test
      systems that might better predict their clinical outcome. Many of these
      approaches and test systems may be applicable to other viral systems being
      developed as oncolytic agents.

PMID- 16955696
TI  - Exploiting the properties of adult stem cells for the treatment of disease.
AB  - Much of the current hope in regenerative medicine is intimately entwined with
      promises that stern cells will provide the backbone for cell-replacement
      therapies to treat various degenerative, genetic and malignant conditions. The
      realization that a wide range of adult tissues contain stem cells has heightened
      this optimism, and ultimately the expectation that these somatic cells can be
      harnessed to provide cell-based therapies that will soon be realized in the
      clinic. This review discusses the recent advances in adult stem-cell technology
      that have captured significant attention and discusses progress in the
      development of two distinct methodologies currently being exploited in
      regenerative medicine strategies.

PMID- 16955697
TI  - The therapeutic potential of embryonic stem cells: A focus on stem cell
      stability.
AB  - Most therapeutic uses of stem cells demand that large numbers of cells are
      maintained in a Good Manufacturing Practice (GMP) facility, and envisage the
      development of a master depository from which a working bank of cells can be
      retrieved and differentiated into an appropriate phenotype for use. Likewise for
      gene- and drug-discovery processes, it is assumed that stable and genetically
      identical cells will eventually become available in large numbers. Critical for
      both of these assumptions is that the stem cells are stable during periods of
      amplification and differentiation. This review discusses the physiological
      features that must be assessed to measure stem cell stability, and proposes that
      genomic, epigenomic and mitochondrial markers, as well as functional measures of
      utility, should be considered. Recent findings suggesting that the level of cell
      stability is not homogeneous throughout all stem cells are also discussed.

PMID- 16955698
TI  - Adult neurogenesis in mammals.
AB  - With the recent confirmation that neurogenesis occurs in the adult brain, and
      that neural stem cells reside in the adult central nervous system (CNS), the
      function of newly generated neuronal cells in the adult brain is the source of
      intense research and debate. Neurogenesis is modulated by a wide variety of
      physiopathological conditions and environmental stimuli, offering the possibility
      that newly generated neuronal cells might be functionally associated with the
      response to these processes. Newly generated neuronal cells in the hippocampus
      have also been implicated in mechanisms of learning, memory and depression.
      However, a number of studies have challenged some of these findings, and the
      roles of newly generated neuronal cells in the functioning of the CNS remain to
      be fully understood. Neurogenesis has been shown to increase bilaterally in the
      adult brain and new neuronal cells are generated at sites of degeneration in the
      brain during disease and after injuries. Taken together, these findings suggest
      that new neuronal cells may be involved in processes such as homeostasis of brain
      tissue, regeneration, plasticity, and neuroadaptation.

PMID- 16955699
TI  - Drug evaluation: LB-80380--a novel phosphonate nucleoside for the potential
      treatment of HBV infection.
AB  - LG Life Sciences Ltd (formerly LG Chem Ltd), in collaboration with Anadys
      Pharmaceuticals Inc, is developing LB-80380 (PMCDG dipivoxil), an orally
      available lead compound in a series of phosphonate nucleotides, for the potential
      treatment of hepatitis B virus infection. In April 2003, phase II trials were
      initiated, the results of which were reported in February 2006. LB-80380 is the
      prodrug of LB-80317 (PMCDG), another compound from this series.

PMID- 16955700
TI  - Drug evaluation: IGN-101--an anti-EpCAM murine antibody vaccine for cancer.
AB  - Igeneon GmbH, a wholly owned subsidiary of Aphton Corp, is developing IGN-101, an
      anticancer vaccine containing the EpCAM-targeting aluminum-adsorbed munrine
      monoclonal antibody 17-1A (edrecolomab), for the potential subcutaneous treatment
      of epithelial cancers such as colorectal and rectal tumors. By February 2004,
      Igeneon was seeking to outlicense the drug.

PMID- 16955701
TI  - Cell death in the nervous system.

PMID- 16955702
TI  - The glial response to injury and its role in the inhibition of CNS repair.

PMID- 16955703
TI  - DSD-1-Proteoglycan/Phosphacan and receptor protein tyrosine phosphatase-beta
      isoforms during development and regeneration of neural tissues.
AB  - Interactions between neurons and glial cells play important roles in regulating
      key events of development and regeneration of the CNS. Thus, migrating neurons
      are partly guided by radial glia to their target, and glial scaffolds direct the
      growth and directional choice of advancing axons, e.g., at the midline. In the
      adult, reactive astrocytes and myelin components play a pivotal role in the
      inhibition of regeneration. The past years have shown that astrocytic functions
      are mediated on the molecular level by extracellular matrix components, which
      include various glycoproteins and proteoglycans. One important, developmentally
      regulated chondroitin sulfate proteoglycan is DSD-1-PG/phosphacan, a glial
      derived proteoglycan which represents a splice variant of the receptor protein
      tyrosine phosphatase (RPTP)-beta (also known as PTP-zeta). Current evidence
      suggests that this proteoglycan influences axon growth in development and
      regeneration, displaying inhibitory or stimulatory effects dependent on the mode
      of presentation, and the neuronal lineage. These effects seem to be mediated by
      neuronal receptors of the Ig-CAM superfamily.

PMID- 16955704
TI  - Regeneration failure in the CNs: cellular and molecular mechanisms.

PMID- 16955705
TI  - The role of ionotropic purinergic receptors (P2X) in mediating plasticity
      responses in the central nervous system.

PMID- 16955706
TI  - Lesion-induced axonal sprouting in the central nervous system.
AB  - Injury or neuronal death often come about as a result of brain disorders.
      Inasmuch as the damaged nerve cells are interconnected via projections to other
      regions of the brain, such lesions lead to axonal loss in distal target areas.
      The central nervous system responds to deafferentation by means of plastic
      remodeling processes, in particular by inducing outgrowth of new axon collaterals
      from surviving neurons (collateral sprouting). These sprouting processes result
      in a partial reinnervation, new circuitry, and functional changes within the
      deafferented brain regions. Lesioning of the entorhinal cortex is an established
      model system for studying the phenomenon of axonal sprouting. Using this model
      system, it could be shown that the sprouting process respects the pre-existing
      lamination pattern of the deafferented fascia dentata, i. e., it is layer
      specific. A variety of different molecules are involved in regulating this
      reorganization process (extracellular matrix molecules, cell adhesion molecules,
      transcription factors, neurotrophic factors, growth-associated proteins). It is
      proposed here that molecules of the extracellular matrix define the boundaries of
      the laminae following entorhinal lesioning and in so doing limit the sprouting
      process to the deafferented zone. To illustrate the role of axonal sprouting in
      disease processes, special attention is given to its significance for
      neurodegenerative disorders, particularly Alzheimer's disease (AD), and temporal
      lobe epilepsy. Finally, we discuss both the beneficial as well as disadvantageous
      functional implications of axonal sprouting for the injured organism in question.

PMID- 16955707
TI  - A kinase with a vision: Role of ERK in the synaptic plasticity of the visual
      cortex.

PMID- 16955708
TI  - Attempts to restore visual function after optic nerve damage in adult mammals.
AB  - Retinal ganglion cells (RGCs) and their axons, i.e., optic nerve (ON) fibers,
      provide a good experimental model for research on damaged CNS neurons and their
      functional ecovery. After the ON transection most RGCs undergo retrograde and
      anterograde degeneration but they can be rescued and regenerated by
      transplantation of a piece of peripheral nerve (PN). When the nerve graft was
      bridged to the visual center, regenerating RGC axons can restore the central
      visual projection. Behavioral recovery of relatively simple visual function has
      been proved in such PN-grafted rodents. Intravitreal injections of various
      neurotrophic factors and cytokines to activate intracellular signaling mechanism
      of RGCs and electrical stimulation to the cut end of ON have promoting effects on
      their survival and axonal regeneration. Axotomized RGCs in adult cats are also
      shown to survive and regenerate their axons through the PN graft. Among the cat
      RGC types, Y cells, which function as visual motion detector, tend to survive and
      regenerate axons better than others. X cells, which are essential for acute
      vision, suffer from rapid death after ON transection but they can be rescued by
      intravitreal application of neurotrophins accompanied with elevation of cAMP. To
      restore visual function in adult mammals with damaged optic pathway, the
      comprehensive and integrative strategies of multiple approaches will be needed,
      taking care of functional diversity of RGC types.

PMID- 16955709
TI  - Brain repair: Experimental treatment strategies, neuroprotective and repair
      strategies in the lesioned adult CNS.

PMID- 16955710
TI  - Neuroprotection by cAMP: Another brick in the wall.
AB  - Programmed cell death occurs in the nervous system both in normal development as
      well as in pathologic conditions, and is a key issue related to both brain repair
      and neurodegenerative diseases. Modulation of cell death in the nervous system
      may involve neurotrophic factors and other peptides, neurotransmitters and
      neuromodulators, that activate various signal transduction pathways, which in
      turn interact with the cell death execution machinery. Here we discuss the role
      of the second messenger cyclic adenosine 3'5'-monophosphate (cAMP) in cell death,
      and summarize current evidence that cAMP is a nodal point of neuroprotective
      signaling pathways.

PMID- 16955711
TI  - The collagenous wound healing scar in the injured central nervous system inhibits
      axonal regeneration.
AB  - Following traumatic injuries of the central nervous system (CNS) a wound healing
      scar, resembling the molecular structure of a basement membrane and mainly
      composed of Collagen type IV and associated glycoproteins and proteoglycans, is
      formed. It is well known that CNS fibers poorly regenerate after traumatic
      injuries. In this article we summarize data showing that prevention of collagen
      scar formation enables severed axons in brain and spinal cord to regrow across
      the lesion site and to elongate in uninjured CNS tissue. We observed that
      regenerating fibers grow back to their former target where they develop chemical
      synapses, become remyelinated by resident oligodendrocytes and conduct action
      potentials.

PMID- 16955712
TI  - Role of endogenous neural stem cells in neurological disease and brain repair.
AB  - These examples show that stem-cell-based therapy of neuro-psychiatric disorders
      will not follow a single scheme, but rather include widely different approaches.
      This is in accordance with the notion that the impact of stem cell biology on
      neurology will be fundamental, providing a shift in perspective, rather than
      introducing just one novel therapeutic tool. Stem cell biology, much like
      genomics and proteomics, offers a "view from within" with an emphasis on a
      theoretical or real potential and thereby the inherent openness, which is central
      to the concept of stem cells. Thus, stem cell biology influences many other, more
      traditional therapeutic approaches, rather than introducing one distinct novel
      form of therapy. Substantial advances have been made i n neural stemcell research
      during the years. With the identification of stem and progenitor cells in the
      adult brain and the complex interaction of different stem cell compartments in
      the CNS--both, under physiological and pathological conditions--new questions
      arise: What is the lineage relationship between t he different progenitor cells
      in the CNS and how much lineage plasticity exists? What are the signals
      controlling proliferation and differentiation of neural stem cells and can these
      be utilized to allow repair of the CNS? Insights in these questions will help to
      better understand the role of stem cells during development and aging and the
      possible relation of impaired or disrupted stem cell function and their impact on
      both the development and treatment of neurological disease. A number o f studies
      have indicated a limited neuronal and glial regeneration certain pathological
      conditions. These fundamental observations have already changed our view on
      understanding neurological disease and the brain's capacity for endogenous
      repair. The following years will have to show how we can influence andmodulate
      endogenous repair nisms by increasing the cellular plasticity in the young and
      aged CNS.

PMID- 16955713
TI  - Transplantation in Parkinson's disease: The future looks bright.

PMID- 16955714
TI  - Treatment planning the edentulous mandible.

PMID- 16955715
TI  - Principles and technique of using bonded post and cores.
AB  - This article discusses today's principles of adhesive dentistry and proposes new,
      conservative guidelines and techniques for post space preparation and post length
      for bonded post and cores. Also discussed is a technique using dual-cure
      composite resin and glass fiber posts to effectively perform a bonded post and
      core build-up procedure.

PMID- 16955716
TI  - Building the edentulous impression--a layering technique using multiple
      viscosities of impression material.
AB  - The purpose of this article is to introduce a novel impression technique. The
      procedure demonstrates a building, or layering, method of impression making that
      maintains the integrity between layers of the impression materials of varying
      viscosities and controls the path of insertion, minimizing the incidence of
      overextension. To build a detailed impression of the tissue-bearing surfaces, the
      clinician selects the proper viscosity of impression material based on the
      diagnosed tissue condition.

PMID- 16955717
TI  - Practical oral sedation in dentistry, part I: pre-sedation consideration and
      preparation.
AB  - This article presents a practical approach for safe oral sedation in dentistry.
      When properly done, oral sedation can provide comfort and a calming treatment
      environment for patients whose fears inhibit them from securing needed dental
      care. The authors provide information on medico-legal aspects of sedation,
      patient treatment recommendations, counseling, evaluation, monitoring,
      documentation, and proper discharge procedures. The reliable sedatives that have
      undergone years of clinical trials with a good safety record and predictable
      results are presented. For each sedative drug, the description, formulation and
      dosage, onset, duration of sedation, Oral and side effects are discussed in a 2
      part presentation.

PMID- 16955718
TI  - Correlation between occlusion and cervical posture in patients with bruxism.
AB  - The goal of this study was to evaluate head and neck posture in the rest position
      of patients with bruxism and patients without temporomandibular disorder signs or
      symptoms to further relate them with Angle's class of malocclusion. Fifty-six
      volunteers participated in this study, ages 18 to 27 years with an average age of
      22.5 years. They were divided into 2 groups: Group B--28 subjects with
      parafunctions (teeth grinding or clenching); and Group C--28 subjects without
      parafunctional habits (control group). All participants were photographed, and
      their pictures were analyzed and compared with the software Alcimagem
      (Instrumental Concept and Movement Analysis Laboratory, Uberlandia, Minas Gerais,
      Brazil). The results demonstrated that variation of angular values did not
      present statistical difference for the studied groups. Regarding Angle's class of
      malocclusion, class I was predominant in Group C, and classes II and III were
      predominant in Group B. The mental-sternal angle calculated did not present
      statistical significance between the groups; however, there was a greater
      variation between the smaller angle and the higher angle in Group B, contrary to
      Group C.

PMID- 16955719
TI  - Evaluating technology for your practice.

PMID- 16955720
TI  - Influence of graded magnesium deficiencies on white blood cell counts and
      lymphocyte subpopulations in rats.
AB  - Increased white blood cell counts or leukocytosis have been observed primarily in
      young rats fed diets extremely low in Mg (< 60 ppm) and high in phosphorus (0.5 %
      P). We investigated the influence that acute and moderate Mg deficiencies have on
      blood leukocytes at high and low dietary phosphorus levels. For four weeks, male
      Sprague-Dawley rats (initially 7 weeks old) were fed diets containing 30, 60,
      120, 208, or 850 ppm Mg and either 0.3 % or 0.5 % dietary phosphorus. Total
      leukocytes were increased in rats fed 30 ppm Mg (p < 0.0001), and the leukocyte
      subpopulation counts of lymphocytes, neutrophils, monocytes and eosinophils
      increased significantly only in the rats fed 30 ppm Mg (p < 0.0001). B-cells
      decreased significantly as a percentage of lymphocytes (p < 0.0093) as dietary Mg
      decreased. As total counts in blood, B-cells, CD4 and CD8 cells were
      significantly increased in the rats consuming the 30 ppm Mg diet. Dietary
      phosphorus only had an effect in combination with the lowest dietary Mg. These
      results demonstrate a threshold effect for increased leukocytes during a Mg
      deficiency of four weeks. A Mg deficiency of a longer duration may show different
      results.

PMID- 16955721
TI  - Anxiety and stress among science students. Study of calcium and magnesium
      alterations.
AB  - Stress and anxiety of university science students (Chemistry) was evaluated in
      basal conditions and during exams using validated stress and anxiety
      questionnaires. The relations between the data obtained and various biochemical
      markers were established. Results showed that the evaluated students did not
      experience stress increase as a consequence of exams but suffered a significant
      increase in anxiety. The psychological findings agree with the urinary biomarkers
      studied. It is known that anxiety is related to partial magnesium reduction
      associated with a urinary magnesium excretion increase, as observed in the
      present data. Nevertheless, stress also correlates with a urinary calcium
      increase which was not detected in the present study.

PMID- 16955722
TI  - Changes of blood magnesium concentration in patients undergoing surgical
      myocardial revascularisation.
AB  - BACKGROUND: Magnesium (Mg) is the second most relevant intracellular element,
      which plays an important role in many physiological processes. Magnesium
      disorders are particularly important in haemodynamically unstable patients, such
      as patients after extracorporeal circulation. The aim of this study was to
      analyze the changes in blood Mg levels in patients undergoing coronary artery
      bypass procedures with extracorporeal circulation. PATIENTS AND METHODS: Twenty
      male patients, aged 50-69, undergoing CABG with ECC under general anaesthesia,
      were included in the study. All of them were operated on due to Io and IIo degree
      coronary disease (according to CCS). The blood concentrations of Mg were examined
      in five stages: 1) before the induction of anaesthesia; 2) during extracorporeal
      circulation; 3) after surgery; 4) in the morning of the first postoperative day;
      5) in the morning of the second postoperative day. The blood Mg concentrations
      were determined by spectrophotometric methods. RESULTS: The blood concentration
      of Mg decreased during extracorporeal circulation and immediately after surgery
      and increased in the morning of the first and second postoperative days.
      CONCLUSION: The CABG with extracorporeal circulation resulted in a significant
      decrease in blood Mg concentration.

PMID- 16955724
TI  - Is magnesium neuroprotective following global and focal cerebral ischaemia? A
      review of published studies.
AB  - Neuroprotective activity with magnesium associated with animal models of cerebral
      ischaemia, seizure, perinatal hypoxia/ischaemia, subarachnoid haemorrhage and
      traumatic brain injury has provided the justification for clinical stroke trials.
      However, the recent IMAGES stroke clinical trial found magnesium to be largely
      ineffective. Hence, due to the negative stroke trial outcome, current FAST-MAG
      trial and our own experience with magnesium in cerebral ischaemia animal models,
      we thought it prudent to review these preclinical and clinical studies. We
      reviewed nine studies describing the use of magnesium following global cerebral
      ischaemia and fourteen following focal cerebral ischaemia. Four global ischaemia
      and six focal ischaemia studies did not show a significant neuroprotective effect
      with magnesium. In the majority of positive magnesium studies animal body
      temperature was not monitored post-ischaemia. Thus the effects of post-ischaemic
      hypothermia cannot be ruled out as a confounding factor in positive magnesium
      cerebral ischaemia studies. Moreover, data from our own laboratory indicates that
      magnesium is only neuroprotective when combined with post-ischaemic hypothermia.
      These data provide a possible explanation of why the IMAGES trial was largely
      unsuccessful, as current stroke patient management does not involve hypothermia
      induction. Future preclinical and clinical cerebral ischaemia trials with
      magnesium should consider combining treatment with mild hypothermia.

PMID- 16955723
TI  - The effect of preoperative magnesium supplementation on blood catecholamine
      concentrations in patients undergoing CABG.
AB  - BACKGROUND: It is well known that magnesium (Mg) plays an important role in many
      physiological processes such as regulation of blood catecholamine concentrations,
      particularly epinephrine (E) and norepinephrine (NE). The complex character of
      extracorporeal circulation (ECC) with intraoperative normovolemic haemodilution
      (NH) may alter blood Mg levels, which is likely to result in disorders of E and
      NE. The aim of this study was to analyze the influence of preoperative Mg
      supplementation on E and NE in patients undergoing CABG. PATIENTS AND METHODS:
      Forty male patients undergoing CABG under general anaesthesia were included.
      Patients were randomly divided into two groups: A--the patients receiving pre
      operative magnesium supplementation and B--patients without pre-operative
      magnesium supplementation. The Mg, E and NE blood concentrations were measured in
      five stages: 1) before anesthesia after the radial artery cannulation, 2) during
      NH and ECC, 3) immediately after surgery, 4) in the morning of the 1st
      postoperative day, 5) in the morning of the 2nd postoperative day. The Mg levels
      were determined by spectrophotometric methods, E and NE were measured by
      radioimmunoassay methods. RESULTS: The CABG caused a decrease of Mg and an
      increase of E and NE in both groups, but the changes were significantly higher in
      group B. CONCLUSIONS: 1) CABG causes a decrease of Mg and an increase of E and
      NE; 2) Preoperative, oral supplementation of Mg substantially reduces intra- and
      postoperative disorders.

PMID- 16955725
TI  - Directional verbal probabilities: inconsistencies between preferential judgments
      and numerical meanings.
AB  - Verbal probability expressions (e.g., it is possible or doubtful) convey not only
      vague numerical meanings (i.e., probability) but also semantic functions, called
      directionality. We performed two experiments to examine whether preferential
      judgments are consistent with numerical meanings of verbal probabilities
      regardless of directionality. The results showed that because of the effects of
      directionality, perceived degrees of certainty for verbal probabilities differed
      between a binary choice and a numerical translation (Experiment 1), and decisions
      based on a verbal probability do not correspond to those based on a numerical
      translation for verbal probabilities (Experiment 2). These findings suggest that
      directionality of verbal probabilities is an independent feature from numerical
      meanings; hence numerical meanings of verbal probability alone remain
      insufficient to explain the effects of directionality on preferential judgments.

PMID- 16955726
TI  - Wayfinding behavior and spatial knowledge of adults and children in a virtual
      environment: The role of landmarks.
AB  - This study investigated the effect of different organizations of landmark
      location pairings as fine-space information on wayfinding behavior and spatial
      knowledge on a total of 90 participants: 30 second graders, 30 sixth graders, and
      30 adults. All participants had to find their way to a goal in a virtual
      environment with either randomized or categorical landmarks, or without any
      landmarks. Thereafter, they had to find the shortest way from the start position
      to the goal in two consecutive trials (wayfinding performance), and they had to
      solve a number of spatial knowledge tasks. The results showed that independent of
      their categorical function, the existence of landmarks influenced the way-finding
      performance of adults and children in the same way. Whereas the presence of
      landmarks had no effect on spatial survey knowledge, landmark knowledge itself
      was influenced by the categorical function of the landmarks presented. Moreover,
      second graders showed limited achievement compared to adults independent of the
      existence of landmarks. The main results implicate firstly that children at
      school age indeed are able to use landmark-location pairings as fine-space
      information like adults during learning an unknown environmental space, and
      secondly that a dissociation between wayfinding behavior and spatial knowledge
      might exist.

PMID- 16955727
TI  - Delayed masking and the auditory attentional blink: A test for retrieval
      competition and bottleneck models.
AB  - The attentional blink (AB) corresponds to a transient deficit in reporting the
      second (T2) of two targets embedded in a rapid sequence of distractors. The
      retrieval competition (Shapiro, Raymond & Arnell, 1994) and bottleneck models
      (Chun & Potter, 1995; Jolicoeur, 1998) predict the attenuation of the deficit
      with the extension of the delay between T2 and its mask. This prediction was
      tested using auditory sequences of nonverbal stimuli in which the T2-mask
      interval was systematically varied. The magnitude of the auditory AB diminished
      with the lengthening of the interval from 50 to 150 ms while no time-locked
      deficit was observed with the longest (350 ms) and the shortest (10 ms)
      intervals. These results suggest that presenting a mask after T2 is not
      sufficient to produce an auditory AB: The mask must be perceivable as an auditory
      event distinct from the target and occur before T2 consolidation. The present
      study also provides evidence that as in vision, AB deficits take place in the
      auditory domain when T2 is masked by interruption but not by integration. Our
      findings are best accounted for in terms of bottlenecked processing limitations.

PMID- 16955728
TI  - Working memory involvement in emotion-based processes underlying choosing
      advantageously.
AB  - The Iowa Gambling Task (IGT) is widely used to assess decision making under
      conditions of uncertainty in clinical as well as in nonclinical populations.
      However, there is still debate as to whether normal performance at this task
      relies on implicit, emotion-based processes that are independent of working
      memory. To clarify the role of working memory on normal performance on the IGT,
      participants performed the task under low or high working memory load. We used a
      modified version of the original task, in which the position of the four decks
      was randomized between trials. Results showed that only participants performing
      under low memory load significantly chose more advantageously halfway through the
      task. In addition, when comparing the number of cards chosen from the two decks
      with frequent losses, one advantageous and one disadvantageous, only participants
      performing under low memory load chose more cards from the advantageous deck. The
      present findings indicate that the processes underlying optimal advantageous
      performance on the IGT rely on working memory functions.

PMID- 16955729
TI  - Does solution of mental arithmetic problems such as 2 + 6 and 3 x 8 rely on the
      process of "Memory updating"?
AB  - Two experiments are reported that used the selective interference paradigm to
      study whether, besides response selection, the process of memory updating is
      involved in simple mental arithmetic. Participants were asked to solve simple
      sums (e.g., 2 + 6, Experiment 1) or simple products (e.g., 3 X 8, Experiment 2)
      in a single-task control condition and in three dual-task conditions with a
      selective interference task, simple reactions, choice reactions, or delayed
      choice reactions. The role of memory updating was estimated on the basis of the
      difference in impairment due to the choice reaction time and the delayed choice
      reaction time task, whereas the difference in impairment between the simple
      reaction time and the choice reaction time task indicates the role of response
      selection. While replicating previous results concerning response selection
      (Deschuyteneer & Vandierendonck, 2005, in press), the study showed that memory
      updating is strongly involved in solving simple mental arithmetic sums and
      products.

PMID- 16955730
TI  - Individual performance based on cognitive experimental measurements? The case of
      inhibition of return.
AB  - Inhibition of Return (IOR) is a mechanism whereby the attentional system favors
      novel locations by inhibiting already scanned ones. In spatial attention tasks,
      it commonly occurs when the interval between cue onset and target onset is longer
      than 300 ms. The positive difference between reactions in the valid condition and
      those in the invalid one shows that responses to target stimuli are slower
      following a valid cue than responses to target stimuli following an invalid cue.
      IOR is a very robust phenomenon at the group mean level; however, this study
      demonstrates that its standard error of measurement is extremely high, which
      seriously challenges any attempt to interpret an individual score as representing
      the characteristics of a subject's attention system. Furthermore, this
      reliability problem might diminish the likelihood of finding differences between
      groups and conditions. The study shows that these problems may be partially
      corrected by employing the back-to-center paradigm.

PMID- 16955731
TI  - Software for generating psychological experiments.
AB  - This review compares four software packages for generating and running
      psychological computer experiments. It aims to inform researchers' decisions
      about which software to choose for their lab. Four widely used general purpose
      commercial packages available for the Windows platform are considered: DirectRT,
      E-Prime, Inquisit, and SuperLab. An overview of each package is given, and the
      implementation of two test experiments is described. Packages are evaluated with
      regard to the amount of complexity reduction they provide for the task of
      programming an experiment and the variety of experimental designs they can
      accommodate.

PMID- 16955732
TI  - The mere exposure effect is sensitive to color information: evidence for color
      effects in a perceptual implicit memory test.
AB  - Priming effects in perceptual tests of implicit memory are assumed to be
      perceptually specific. Surprisingly, changing object colors from study to test
      did not diminish priming in most previous studies. However, these studies used
      implicit tests that are based on object identification, which mainly depends on
      the analysis of the object shape and therefore operates color-independently. The
      present study shows that color effects can be found in perceptual implicit tests
      when the test task requires the processing of color information. In Experiment 1,
      reliable color priming was found in a mere exposure design (preference test). In
      Experiment 2, the preference test was contrasted with a conceptually driven color
      choice test. Altering the shape of object from study to test resulted in
      significant priming in the color-choice test but eliminated priming in the
      preference test. Preference judgments thus largely depend on perceptual
      processes. In Experiment 3, the preference and the color-choice test were studied
      under explicit test instructions. Differences in reaction times between the
      implicit and the explicit test suggest that the implicit test results were not an
      artifact of explicit retrieval attempts. In contrast with previous assumptions,
      it is therefore concluded that color is part of the representation that mediates
      perceptual priming.

PMID- 16955733
TI  - Overexpression and characterization of a novel chitinase gene from a marine
      bacterium Pseudomonas sp. BK1.
AB  - The chitinase A (ChiA)-coding gene of Pseudomonas sp. BK1, which was isolated
      from a marine red alga Porphyra dentata, was cloned and expressed in Escherichia
      coli. The structural gene consists of 1602 bp encoding a protein of 534 amino
      acids, with a predicted molecular weight of 55,370 Da. The deduced amino acid
      sequence of ChiA showed low identity (less than 32%) with other bacterial
      chitinases. The ChiA was composed of multiple domains, unlike the arrangement of
      domains in other bacterial chitinases. Recombinant ChiA overproduced as inclusion
      bodies was solubilized in the presence of 8 M urea, purified in a urea-denatured
      form and re-folded by removing urea. The purified enzyme showed maximum activity
      at pH 5.0 and 40 degrees C. It exhibited high activity towards glycol chitosan
      and glycol chitin, and lower activity towards colloidal chitin. The enzyme
      hydrolyzed the oligosaccharides from (GlcNAc)4 to (GlcNAc)6, but not GlcNAc to
      (GlcNAc)3. The results suggest that the ChiA is a novel enzyme, with different
      domain structure and action mode from bacterial family 18 chitinases.

PMID- 16955734
TI  - Dietary restriction and triiodothyronine (T3) regulation of malate-aspartate
      shuttle enzymes in the liver and kidney of mice.
AB  - The activities of malate-aspartate shuttle enzymes viz., cytosolic and
      mitochondrial aspartate aminotransferase (c- and m-AsAT) and malate dehydrogenase
      (c- and m-MDH) were measured in liver and kidney of ad libitum (AL) and dietary
      restricted (DR) mice and also on triiodothyronine (T3) treatment. The results
      show that the activity (U/mg protein) of c-AsAT is increased significantly in
      liver and the activities of c-MDH and m-AsAT are increased significantly in
      kidney during DR. On T3 treatment, the activities of both the isoenzymes (c- and
      m-) of MDH and AsAT are increased significantly in the liver of AL- and DR-fed
      mice. In the kidney, m-MDH showed no effect by T3 treatment, however, c-MDH
      increased significantly in both AL- and DR-fed mice. In contrast, m-AsAT is
      increased significantly in the kidney in AL-fed mice, but was not affected in DR
      fed animals. In vitro reconstitution of malate-aspartate shuttle showed a higher
      activity in the liver and kidney of DR-fed mice, as compared to AL-fed ones and
      also in the T3-treated mice, compared to untreated ones. These findings suggest
      that malate-aspartate shuttle enzymes are differentially regulated during DR in
      mice, in order to adapt to the metabolic need of liver and kidney. T3 potentially
      regulates the shuttle enzymes, albeit to a varying degree in the liver and kidney
      of AL- and DR-fed mice.

PMID- 16955735
TI  - Production of human single-chain variable fragment (scFv) antibody specific for
      digoxin by ribosome display.
AB  - Ribosome display was applied in vitro to select single-chain variable fragment
      (scFv) antibody specific for digoxin from a human non-immune naive scFv library.
      A cell-free system was used to produce stable antibody-ribosome-mRNA (ARM)
      complexes to provide the linkage of genotype and phenotype, allowing simultaneous
      selection of a desired antibody together with its encoding mRNA. The mRNA was
      then recovered and amplified as DNA by reverse transcriptase-polymerase chain
      reaction (RT-PCR). Repeating the display cycle enriched the selected molecules,
      enabling rare species to be isolated. In this study, digoxin-binding segments
      were selected over four cycles of ARM display and the selected DNA was cloned and
      expressed as a single-chain variable fragment antibody (the best scFv, A3) in
      Escherichia coli. The affinity (equilibrium dissociation constant Kd) of digoxin
      was 8.3 x 10(-8) M for A3, which validated construction of the naive library and
      the power of ribosome display lending to the evolution of functional
      characteristics, such as potency of leading candidate antibodies to provide
      therapeutic antibodies. A3 was purified using affinity chromatography and
      determined by Western blot. The results indicate that ribosome display technnique
      can be efficiently used to isolate specific antibody fragments from a naive
      library.

PMID- 16955737
TI  - Expression of delta1-pyrroline-5-carboxylate synthetase gene during drought in
      rice (Oryza sativa L.).
AB  - The 45-days-old seedlings of drought resistant (N-22, CR143-2-2) and susceptible
      rice (Oryza sativa L.) genotypes (Panidhan, Pusa-169) were subjected to osmotic
      stress in PEG-6000 solution of -10 and -16 bar and the relative water content
      (RWC), proline content, and pyrroline-5-carboxylate synthetase (P5CS) activity
      and its P5CS expression were studied. A gradual decrease in RWC was observed in
      tolerant genotypes, whereas the decrease was drastic in susceptible ones. Proline
      content and P5CS activity increased both in susceptible and tolerant genotypes;
      the increase was higher in tolerant genotypes. Higher proline levels in tolerant
      genotypes were due to increased P5CS activity. The EcoRI, BamHI and XbaI
      restricted DNA of N-22 and Panidhan genotypes were hybridized with Arabidopsis
      P5CS sequence and a single band (approx 2.4 kb) was observed, however, P5CS
      expression was more in N-22 as compared to Panidhan.

PMID- 16955736
TI  - Correlation of HER1/EGFR expression and degree of radiosensitizing effect of the
      HER1/EGFR-tyrosine kinase inhibitor erlotinib.
AB  - Epidermal growth factor receptor (HER1/EGFR)-mediated signal transduction
      pathways are important in cellular response to ionizing radiation. High HER1/EGFR
      expression on cancer cells may contribute to radioresistance. In this pre
      clinical study, we evaluated the radiosensitizing effect of erlotinib, a small
      molecule HER1/EGFR inhibitor in three human cancer cell lines with different
      HER1/EGFR expression--A431 (very high expression), H157 (moderate expression) and
      H460 (low expression). Our results demonstrated that A431 was the most
      radioresistant, while H460 was the most radiosensitive. However, A431 cells were
      the most sensitive to erlotinib (IC50 = 300 nM) and H460 cells the most resistant
      (IC50 = 8 microM). H157 had intermediate sensitivity to radiation and erlotinib
      (IC50 = 3 microM). With 300 nM erlotinib, the radiation dose enhancement ratios
      (DER) were 1.40, 1.17 and 1.04 in A431, H157 and H460, respectively. Treatment
      with erlotinib for 24 hr at 300 nM increased G1 arrest by 18.6, 2.0 and 4.8% in
      A431, H157 and H460, respectively. Erlotinib-induced apoptosis was augmented by
      radiation in A431 cells only. In conclusion, high HER1/EGFR expression may result
      in a high degree of radiosensitization with erlotinib combined with radiation.
      The extent of erlotinib-induced radiosensitization was proportional to HER1/EGFR
      expression, as well as autophosphorylation of the human epidermal growth factor
      receptor (HER1/EGFR).

PMID- 16955738
TI  - Induction of resistance in host against the infection of leaf blight pathogen
      (Alternaria palandui) in onion (Allium cepa var aggregatum).
AB  - The Pseudomonas fluorescens isolate Pfl was found to inhibit the growth of
      pathogen Alternaria palandui, in vitro. In the present study, foliar application
      of a talc-based formulation of Pfl significantly reduced the incidence of leaf
      blight of onion, caused by A. palandui. Induction of defense-related proteins
      viz., chitinase, beta-1,3 glucanase, peroxidase (PO) and polyphenol oxidase (PPO)
      by application of Pfl, was studied against A. palandui infection in resistant
      (IHR 56) and susceptible (MDUI) onion cultivars. Chitinase in both cultivars,
      with or without challenge-inoculation of A. palandui revealed changes in the
      isoform pattern. The Native-PAGE of PO showed induction of PO2 isoform in both
      the cultivars, in response to inoculation of pathogen. Isoform analysis of PPO
      also exhibited induction in the Pfl-treated plants challenged with pathogen.
      Similarly, the activity of beta-1,3-glucanase was greatly induced in Pfl-treated
      plants, challenged with pathogen as compared to controls. Thus, the P.
      fluorescens-treated plants showed significant increase in the levels of the
      defense enzymes, in comparison to the plants challenged with the pathogen.

PMID- 16955739
TI  - Energy barriers and rates of tautomeric transitions in DNA bases: ab initio
      quantum chemical study.
AB  - Tautomeric transitions of DNA bases are proton transfer reactions, which are
      important in biology. These reactions are involved in spontaneous point mutations
      of the genetic material. In the present study, intrinsic reaction coordinates
      (IRC) analyses through ab initio quantum chemical calculations have been carried
      out for the individual DNA bases A, T, G, C and also A:T and G:C base pairs to
      estimate the kinetic and thermodynamic barriers using MP2/6-31G** method for
      tautomeric transitions. Relatively higher values of kinetic barriers (about 50-60
      kcal/mol) have been observed for the single bases, indicating that tautomeric
      alterations of isolated single bases are quite unlikely. On the other hand,
      relatively lower values of the kinetic barriers (about 20-25 kcal/mol) for the
      DNA base pairs A:T and G:C clearly suggest that the tautomeric shifts are much
      more favorable in DNA base pairs than in isolated single bases. The unusual base
      pairing A':C, T':G, C':A or G':T in the daughter DNA molecule, resulting from a
      parent DNA molecule with tautomeric shifts, is found to be stable enough to
      result in a mutation. The transition rate constants for the single DNA bases in
      addition to the base pairs are also calculated by computing the free energy
      differences between the transition states and the reactants.

PMID- 16955740
TI  - Reaction of substituted pyrimidines with photochemically generated t-BuO*
      radicals.
AB  - Humans are exposed to various organic peroxides through chemical, pharmaceutical
      and cosmetic products. On photolysis, these peroxides produce alkoxyl radicals
      and hydroxyl radicals. The reaction of *OH radicals with DNA and its constituents
      have been extensively studied, but very little is known about the reactions of
      alkoxyl radicals with DNA and its constituents. In view of this, the oxidation of
      pyrimidine bases viz., thymine, uracil, cytosine, 5-bromouracil, 6-methyluracil
      and 1,3-dimethyluracil by t-BuO* radicals in aqueous solution at pH 7.5 has been
      carried out. The reaction between pyrimidine and t-BuO* is followed by measuring
      the absorbance of pyrimidine at the respective lambdamax. The rates of oxidation
      of pyrimidines are calculated from the plot of absorbance vs time. The rates of
      oxidation of pyrimidines have been found to increase with increase in [t-BuOOH],
      [pyrimidine] and light intensity. The quantum yields are calculated from the
      initial rates of oxidation of pyrimidine and the measured light intensity at 254
      nm the wavelength at which t-BuOOH is activated to give radicals. The quantum
      yields are found to depend on [pyrimidine] as well as on [t-BuOOH] while they are
      independent of light intensity. The product analysis was carried out on HPLC with
      UV-visible detector. The corresponding 5,6-dihydroxypyrimidine and isobarbituric
      acid have been identified by comparing the retention times of the authentic
      samples. On the basis of experimental results and product analysis, it is
      suggested that t-BuOOH on photolysis gives t-BuO* radical, which initiates the
      reaction by adding to C (5) or C (6) position of pyrimidine base, leading to the
      formation of pyrimidine base radical via hydrolysis. The pyrimidine radical
      further reacts with t-BuO* radical to give the final product. This study predicts
      the probable transient pyrimidine radicals.

PMID- 16955741
TI  - Determination of serum glucose using co-immobilized glucose oxidase and
      peroxidase onto arylamine glass beads affixed on a plastic strip.
AB  - Glucose oxidase (GOD) from Aspergillus niger and horseradish peroxidase (POD)
      were co-immobilized onto arylamine glass beads affixed on a plastic strip with a
      conjugation yield of 28.2 mg/g and 43% retention of their initial specific
      activity. The coimmobilized enzymes showed maximum activity at pH 7.5 when
      incubated at 37 degrees C for 15 min. A simple, specific and sensitive method for
      discrete analysis of the serum glucose was developed employing this strip. The
      minimum detection limit of the method was 5 mg/dl. Within and between assay
      coefficient of variations for the serum were <5.6% and <10.6% (n = 6) respondely.
      A good correlation (r = 0.943) was found between the glucose values obtained by
      the enzyme colorimetric method employing free GOD and POD and the present method.
      The strip lost 50% of its initial activity after its 150 regular uses for a
      period of one month, when stored in reaction buffer at 4 degrees C. The method is
      cost-effective than the enzymic colorimetric method, as the enzyme strip is
      reusable.

PMID- 16955742
TI  - Antibacterial activity of crude methanolic extract and its fractions of aerial
      parts of Anthemis tinctoria.
AB  - The antibacterial activity of the methanolic extract and its fractions of aerial
      parts of Aniheinis tinctoria (Asteraceae) was investigated against representative
      gram-positive Staphylococcus aureus (ATCC 25923) and Enterococcus faecalis (ATCC
      29212) and gram-negative strains Escherichia coli (ATCC 25922) and Pseudomonas
      aeruginosa (ATCC 27853). The activity was concentrated mainly in the
      dichloromethane (DCM) and hexane fractions of crude methanolic extract. The 5 mg
      of DCM extract per disk produced 15-16 mm of inhibition zone against S. aureus
      and P. aeruginosa, however, no activity was found against E. faecalis and E.
      coli. The hexane fraction showed activity against S. aureus, P. aeruginosa and E.
      faecalis. As DCM fraction showed the highest antibacterial activity in the disk
      diffusion assay, the minimum inhibitory concentration (MIC) and minimum
      bactericidal concentration (MBC) values of only this fraction was determined
      against S. aureus and P. aeruginosa. These values were found to be in the range
      of 1.25 to 10 mg/ml.

PMID- 16955743
TI  - Antibacterial activity of some unsymmetrical diorganyltellurium(IV) dichlorides.
AB  - Six unsymmetrical diorganyltellurium(IV) dichlorides RR'TeCl2 (where R= phenacyl
      , 1-naphthacyl-, and styrylacyl- and R' = p-methoxyphenyl, p-hydroxyphenyl-, and
      3-methyl-4-hydoxyphenyl-) were tested for their antibacterial activity against
      gram-positive (Bacillus subtilis ATCC 6633 and Staphylococcus aureus ATCC 25923)
      and gram-negative (Escherichia coli ATCC 25922. Pseudomonas aeruginosa ATCC 27853
      and Salmonella sp.) bacteria. Antibacterial activity was measured by disk
      diffusion method. Inhibition zones demonstrated that all the compounds showed
      good activity against gram-negative strains. Phenacyl (3-methyl-4-hydroxyphenyl)
      tellurium(IV) dichloride and naphthacyl (3-methyl-4-hydroxyphenyl) tellurium(IV)
      dichloride showed significant activity against both gram-positive and gram
      negative strains. Among the tested compounds, the former exhibited maximum
      activity against gram-positive bacteria, while the latter against all the
      bacteria under study and styrylacyl (p-methoxyphenyl) tellurium(IV) dichloride
      against all the three gram-negative bacteria.

PMID- 16955744
TI  - Lead levels in some biological samples of auto-mechanics in Abeokuta, Nigeria.
AB  - Lead levels were determined in the blood, scalp hair and fingernails of 38, all
      male auto-mechanics (aged 18-45 years) from Abeokuta, South-western Nigeria. The
      subjects were classified into four sub-groups based on the period of exposure
      namely: 1-5, 6-10, 11-15, and >16 years. Thirty-two occupationally unexposed
      subjects (mainly office workers) served as the control. The weight, height and
      body mass indexes of all subjects were noted, in addition to other information
      obtained through structured questionnaire. The mean values of blood lead (BPb),
      hair lead (HPb) and fingernail lead (NPb) of the occupationally exposed subjects
      (n=38) were 48.50 +/- 9.08 microg/dL, 17.75 +/- 5.16 microg/g, and 5.92 +/- 3.30
      microg/g respectively, while the corresponding mean values for these parameters
      in the control subjects (n = 32) were 33.(,5 +/- 10.09 microg/dL, 14.30 +/- 5.90
      microg/g and 5.31 +/- 2.77 microg/g respectively. The differences in BPb and HPb
      levels of the two groups were statistically significant (P <0.05 and P <0.01
      respectively), while that of NPb was not significant. The levels of lead in the
      biological samples appeared to have no relationship with the number of years on
      the job. From these results, it was obvious that the higher levels of lead in the
      biological samples of test subjects, compared with those of the controls were
      from environmental sources.

PMID- 16955745
TI  - Antibodies against 9-O-acetylated sialic acids in childhood acute lymphoblastic
      leukemia: a two-year study with 186 samples following protocol MCP 943.
AB  - Initial studies have revealed an enhanced surface expression of 9-O-acetylated
      sialoglycoconjugates (9-OAcSGs) on lymphoblasts concomitant with high titers of
      antibodies (anti-9-OAcSGs) in childhood acute lymphoblastic leukemia (ALL). This
      study was undertaken in 186 coded samples from 69 ALL patients to evaluate if
      antibodies against these sialoglycans could monitor response to the treatment. An
      ELISA was developed using bovine submaxillary mucin (BSM) containing high % of 9
      O-acetylated sialic acids (9-OAcSA) as the capture antigen, to investigate serum
      levels of anti 9-OAcSGs in a single-center series of pediatric, clinically
      diagnosed and immunophenotypically confirmed ALL patients, as compared to 130
      healthy controls. At presentation, a 3.8-fold increase in anti-9-OAcSGs levels
      was detected in 63/69 ALL patients (mean +/- SEM was 102.8 +/- 6.3 microg/ml) as
      compared to normal controls (27.17 +/- 0.76 microg/ml), assay sensitivity being
      91.3%. On an individual basis (n = 25) in patients who were longitudinally
      monitored for two years, a significant decline in their mean +/- SEM of OD405 was
      observed from 0.85 +/- 0.06 to 0.28 +/- 0.03. Additionally, a dot-blot was
      developed to evaluate the proportion of immune-complexed 9-OAcSGs in these
      patients employing achatinin-H, a 9-OAcSA-binding lectin. Our data indicate that
      these economically viable ELISA-based approaches allow for reliable, sensitive
      and rapid diagnosis of ALL. We contend that these disease-specific antibodies
      could be considered as potential markers both for the initial diagnosis of ALL
      and possibly for longitudinal monitoring of the disease.

PMID- 16955746
TI  - Identification and characterization of a new putative c-type lysozyme from
      malaria vector Anopheles stephensi.
AB  - Lysozyme (E.C. 3.2.1.17) activity is reported from the malaria vector Anopheles
      stephensi. The activity was detected in the salivary gland and midgut using
      bacteriolytic radial diffusion assay. Spectrophotometric analysis indicated that
      higher level of lysozyme activity was maintained in both midgut and salivary
      gland tissues. The activity reached the highest level in 4-8 days old mosquitoes.
      Genomic PCR amplification revealed the presence of at least two putative lysozyme
      genes in the mosquito genome. Preliminary analysis of one of the 413 bp genomic
      fragments showed 56% identity to the lysozyme of mosquito A. gambiae. However,
      the nature and origin of the putative cloned lysozyme gene remains elusive.

PMID- 16955747
TI  - Effect of vitamin E on monosodium glutamate induced hepatotoxicity and oxidative
      stress in rats.
AB  - Monosodium glutamate (MSG), administered to rats (by gavage) at a dose of 0.6
      mg/g body weight for 10 days, significantly (P<0.05) induced lipid peroxidation
      (LPO), decreased reduced glutathione (GSH) level and increased the activities of
      glutathione-s-transferase (GST), catalase and superoxide dismutase (SOD) in the
      liver of the animals; these were observed 24 hr after 10 days of administration.
      The activities of alanine aminotransferase (ALT), aspartate aminotransferase
      (AST) and gamma glutamyl transferase (GGT) were also significantly increased in
      the serum, on MSG administration. Vitamin E (0.2 mg/g body wt) co-administered
      with MSG, significantly reduced the LPO, increased the GSH level and decreased
      the hepatic activities of GST, catalase and SOD. The activities of ALT, AST and
      GGT in the serum were also significantly reduced. The results showed that MSG at
      a dose of 0.6 mg/g body wt induced the oxidative stress and hepatotoxicity in
      rats and vitamin E ameliorated MSG-induced oxidative stress and hepatotoxicity.

PMID- 16955748
TI  - Antioxidant potential of C-phycocyanin isolated from cyanobacterial species
      Lyngbya, Phormidium and Spirulina spp.
AB  - The antioxidant activity of C-Phycocyanin (C-PC) isolated from three
      cyanobacterial species Lyngbya (marine), Phormidium (marine) and Spirulina (fresh
      water) was studied in vitro. The results demonstrate that C-PCs from Lyngbya,
      Phormidium and Spirulina spp. are able to scavenge peroxyl radicals (determined
      by crocin bleaching assay) with relative rate constant ratio of 3.13, 1.89 and
      1.8, respectively. C-PCs also scavenge hydroxyl radicals (determined by
      deoxyribose degradation assay) with second order rate constant values of 7.87 x
      10(10), 9.58 x 10(10) and 6.42 x 10(10), respectively. Interestingly, Lyngbya C
      PC is found to be an effective inhibitor of peroxyl radicals (IC50 6.63 microM),
      as compared to Spirulina (IC50 12.15 microM) and Phormidium C-PC (IC50 12.74
      microM) and is close to uric acid (IC50 2.15 microM). Further, the studies
      suggest that the covalently-linked tetrapyrrole chromophore phycocyanobilin is
      involved in the radical scavenging activity of C-PC. The electron spin resonance
      (ESR) spectra of C-PCs indicate the presence of free radical active sites, which
      may play an important role in its radical scavenging property. This is the first
      report on the ESR activity of native C-PCs without perturbations that can cause
      radical formation.

PMID- 16955749
TI  - Development of pharmacophoric model of condensed pyridine and pyrimidine analogs
      as hydroxymethyl glutaryl coenzyme A reductase inhibitors.
AB  - Quantitative structure-activity relationship (QSAR) has been established on a
      series of thirty-eight compounds of four different sets of condensed pyridine and
      pyrimidine analogs, for their hydroxymethyl glutaryl coenzyme (HMG-CoA) reductase
      inhibitor activity, in order to understand the essential structural requirement
      for binding with receptor, in terms of common biophoric and secondary sites
      employing APEX-3D software. Among several 3D pharmacophoric models with different
      sizes and arrangements, one model was selected based on r2 = 0.8, chance<0.001,
      match equivalent to 0.38 and all the 38 compounds were considered. The results
      suggest that hydrophobicity, hydrogen acceptor and optimum steric refractivity
      play a dominant role in the inhibition of HMG-CoA reductase. The information
      obtained from the present study can be used to design and predict more potent
      molecules as HMG-CoA reductase inhibitors, prior to their synthesis.

PMID- 16955750
TI  - Kinetics and mechanism of reduction of ferricytochrome c by glutathione and L
      cysteine: a comparative study.
AB  - The kinetics and mechanism of the reduction of ferricytochrome c [Cyt c(III)] by
      substrates namely glutathione (GSH) and L-cysteine (L-cys) have been investigated
      spectrophotometrically employing [substrate]T >> [Cyt c(III)]T. The reaction
      exhibits first order dependence in [substrate]T and [Cyt c(III)]T. The pseudo
      first order rate constant increases with an increase in pH, indicating that the
      conjugate base form of the HCyt c(III) is a better oxidant than the parent HCyt
      c(III). The electron transfer rate constants between the oxidants and GSH for
      both the k1 and k2 paths are found to be greater than that with L-cysteine.
      Hence, GSH is a better reductant of Cyt c(III) as compared to L-cysteine. A
      suitable mechanism has been proposed on the basis of experimental findings. The
      deprotonation constant for HCyt c(III) and the second order rate constants of k1
      and k2 paths for the present reaction at 25 degrees C have been determined.

PMID- 16955751
TI  - Oxyradical accumulation and rapid deterioration of soybean seeds due to field
      weathering.
AB  - The effect of field weathering on oxyradical accumulation and subsequent changes
      were studied in the seeds of soybean [Glycine max (L.) Merr.] cv. JS 71-05.
      Electron spin resonance (ESR) quantification of oxyradical revealed that field
      weathering plays an important role in acceleration of their accumulation. One
      week of weathering increased the accumulation of oxyradicals to almost 2-fold and
      triggered the deteriorative cascade, by enhancing the lipid peroxidation and
      membrane perturbation, leading to cell death in seed tissues and poor
      germinability and vigour of soybean seeds. Thus, the weather conditions at the
      time of physiological maturity to harvesting of crop are very crucial and the
      field weathering plays a critical role for the maintenance of seed quality.

PMID- 16955752
TI  - Enzymatic characteristics of ligninperoxidases from Penicillium citrinum,
      Fusarium oxysporum and Aspergillus terreus using n-propanol as substrate.
AB  - The activities of ligninperoxidases from Penicillium citrinum MTCC 3565, Fusarium
      oxysporum MTCC 3379 and Aspergillus terreus MTCC 3374 have been assayed and the
      enzymatic characteristics like Km, pH and temperature optima using n-propanol as
      the substrate have been reported. The results suggest that n-propanol can
      substitute veratryl alcohol as substrate for assaying ligninperoxidase activities
      from different fungal strains, without affecting the enzymatic characteristics.
      The above strains were selected, as they were known to secrete ligninperoxidase
      in the liquid culture medium.

PMID- 16955753
TI  - Kinetics and mechanisms of cholesterol esterase inhibition by cardiovascular
      drugs in vitro.
AB  - Cardiovascular drugs such as lovastatin, simvastatin, amlodipine besylate,
      nifedipine, and hydralazine hydrochloride inhibit cholesterol esterase (CEase) in
      vitro. In the present paper, an attempt was made to determine kinetically the
      reaction mechanism for CEase inhibition by these drugs. The inhibition constant,
      Ki, for the mixed-type inhibition of CEase by these drugs in the presence of
      triton-X-100 or taurochloate were measured. Moreover, the pKi values were
      correlated with the molecular weights of these drugs. In conclusion, the fact
      that these drugs lower cholesterol levels in the plasma low-density lipoprotein
      may be partially due to the CEase inhibition by these drugs.

PMID- 16955754
TI  - Contribution of genomics and proteomics in understanding the role of modifying
      factors in Parkinson's disease.
AB  - Parkinson's disease (PD) is a complex neurological disorder, characterized by
      selective degeneration of nigrostriatal dopaminergic neurons. It is a multi
      factorial disease, contributed by a combination of age, genetic and environmental
      factors. Etiology of sporadic PD and mechanism underlying selective loss of
      dopaminergic neurons has not yet been clearly understood. Recent developments in
      genomics and proteomics have revolutionized the research on PD at genetic level.
      Differential gene expression patterns (DNA biochip technology), age-dependent
      complex genetic patterns (SNP genotyping), and protein expression profiles
      (proteomics) of PD patients have started providing the specific and rigorous
      molecular explanation and role of modifying factors in PD. Genomics and
      proteomics are further expected to help in developing biomarkers for diagnosis of
      early onset PD and also to develop valuable and potential therapeutic strategies
      for its treatment. In this review, we have discussed the progress made by
      genomics and proteomics, in understanding the role of modifying factors in PD.

PMID- 16955755
TI  - Isoproterenol ameliorates workstress-induced rat skeletal muscle degeneration.
AB  - Beta-Agonists though have been widely studied for their protein anabolic effects
      in skeletal muscles, but the lipid status under work stress and agonist treatment
      have not been understood well in the skeletal muscles and heart of rat. In the
      present study, adult male Wistar rats were subjected to work overload stress and
      beta agonist isoproterenol treatment (2 mg kg(-1) day(-1) intraperitoneally) to
      examine, whether it attenuates work stress-induced changes or not.
      Simultaneously, beta2 antagonist butoxamine (2 mg kg(-1) day(-1)
      intraperitoneally) was administered to another isoproterenol-treated group. Work
      stress led to myofibrillar degeneration as well as rapid utilization of lipid to
      meet increased energy demands and for muscle repair, which was reflected through
      histochemical localization of lipids and biochemical estimation of cholesterol
      and triglycerides. Significantly decreased cholesterol levels in skeletal muscles
      and heart muscles were noticed. As expected, isoproterenol reversed the
      conditions by raising cholesterol and triglyceride levels significantly in the
      skeletal muscles and also by ameliorating the degenerative changes in muscle
      fibres as induced by work overload. However, severe accumulation of lipids in
      heart infers towards deleterious effects of isoproterenol on heart and thus
      remains a limiting factor for its immediate clinical application. Further
      research is needed to separate desirable effects of beta agonists on skeletal
      muscles from any undesirable effects on the heart, so as to optimize their
      therapeutic potential.

PMID- 16955756
TI  - Induction, purification and characterization of an antibacterial peptide
      scolopendrin I from the venom of centipede Scolopendra subspinipes mutilans.
AB  - The crude venom of the centipede Scolopendra subspinipes mutilans, injected with
      Escherichia coli K12D31 for 3-4 days showed broad-spectrum antimicrobial activity
      against Gram-positive. Gram-negative bacteria and fungi. It showed good
      antibacterial activity against E. coli K12D31 at different temperatures, pH, and
      ionic strengths. The crude venom was heated at 100 degrees C for 30 min,
      centrifuged at 10,000 rpm for 30 min at 4 degrees C and the supernatants were
      obtained, from which an antibacterial fraction having a molecular mass of 3000
      5000 Da, was further separated by ultrafiltration. A homogeneous antibacterial
      peptide named scolopendrin I, having a molecular mass of 4,498 Da, was isolated
      using cation-exchange chromatography and two steps of reverse-phase high
      performance liquid chromatography (RP-HPLC). Scolopendrin I did not show any
      hemolytic and agglutination activities at the concentration below 30 microM.

PMID- 16955757
TI  - Ficus cunia agglutinin for recognition of bacteria.
AB  - Interaction of bacteria with lectin using anti-lectin antibody by ELISA is an
      established method. In the present study, we have devised a simple ELISA using a
      biotinylated lectin and antibiotin-HRP. Ficus cunia agglutinin (FCA), which has
      shown the specificity towards alpha/beta anomers of GlcNAc and other-NAc
      containing sugars like LacNAc and GlcNAcbeta(1-4/6)GlcNAc, was used as a model
      lectin for the study of interaction with immobilized microorganisms on ELISA
      plate. The bacterial cells of E. coli, Pseudomonas aeruginosa, Klebsiella
      pneumoniae, Bacillus subtilis and Staphylococcus aureus showed binding with FCA
      and the degree of binding was dependent on the bacterial surface antigen. This
      method is considered a simple technique to study the lectin-bacteria interaction.

PMID- 16955758
TI  - Discrete analysis of bile acid in serum and bile with 3 alpha-hydroxysteroid
      dehydrogenase and diaphorase immobilized onto alkylamine glass beads.
AB  - 3alpha-Hydroxysteroid dehydrogenase (3alpha-HSD) from Pseudomonas testosteronei
      and diaphorase (lipoyl dehydrogenase) from Clostridium spp were immobilized
      individually onto alkylamine glass beads through glutaraldehyde coupling. A cost
      effective enzymic colorimetric method for determination of bile acid in the serum
      and bile was developed employing mixture of the immobilized enzymes. The method
      was based upon measurement of NADH generated from NAD+ during oxidation of bile
      acid by immobilized 3alpha-HSD with a color reagent consisting of
      nitrobluetetrazolium (NBT) chloride salt and immobilized diaphorase in 0.065 M
      sodium phosphate buffer (pH 7.0). The minimum detection limit of the method was
      4.8 pmol/L in the serum and 19.5 micromol/L in bile. The per cent recovery of
      added bile acid in the serum and bile was 89.1 and 95.0, respectively. Within and
      between batch coefficients of variation (CV) for bile acid determination were
      <1.0% and <0.2% in the serum and <0.2% and <0.6% in bile, respectively. A good
      correlation for bile acid in the serum (r1= 0.95) and in bile (r2 = 0.93) was
      obtained by a standard chemical method (a commonly used method in India) and the
      present method. The mixture of immobilized 3alpha-HSD and diaphorase lost 30% of
      its initial activity after 4 months of regular use. The cost of bile acid
      determination for 100 the serum and bile samples by the present method was found
      to be lower than by a commercially available method (Sigma kit 450-A).

PMID- 16955759
TI  - Exploring selectivity requirements for peripheral versus central benzodiazepine
      receptor binding affinity: QSAR modeling of 2-phenylimidazo[1,2-a]pyridine
      acetamides using topological and physicochemical descriptors.
AB  - Considering the potential of peripheral benzodiazepine receptor (PBR) ligands in
      therapeutic applications and clinical benefit in the management of a large
      spectrum of different indications, quantitative structure-activity relationship
      (QSAR) study has been attempted to explore the structural and physicochemical
      requirements for selectivity of 2-phenylimidazo[1,2-a]pyridineacetamides for
      binding with peripheral over central benzodiazepine receptors (CBRs). For PBR
      binding affinity, molar refractivity (MR) shows a parabolic relation with binding
      affinity suggesting that binding affinity increases with increase in volume of
      the compounds, until it reaches the critical value, after which the affinity
      decreases. The negative coefficients of S_aaN and S_ssNH indicate that binding
      affinity increases with decrease in E-state value of (N/) (aromatic nitrogen) and
      HN< (secondary amino group) fragments. The coefficient of 3XVC and JX term
      indicates the importance of shape and branching for binding affinity. For CBR
      binding affinity, lipophilicity of molecules is detrimental to the binding
      affinity, while presence of hydrogen at Y position is conducive to the activity.
      Selectivity pattern of these ligands for peripheral (cortex) over central
      receptors requires the presence and absence of methyl group at R2 and R3
      positions respectively, and shows the importance of MR and shape parameter.
      Similarly, selectivity of these ligands for peripheral (ovary) over central
      receptors requires the presence and absence of methyl group at R2 and R3
      positions respectively, presence of phenyl group at R1 and R2 positions and
      selectivity relation shows importance of MR, shape and branching.

PMID- 16955760
TI  - Rapid regulatory effect of tri-iodothyronine (T3) on antioxidant enzyme
      activities in a fish Anabas testudineus (Bloch): short-term in vivo and in vitro
      study.
AB  - The short-term action of thyroid hormone tri-iodothyronine (T3) was studied in
      vivo and in vitro on antioxidant enzyme activities in a teleost Anabas
      testudineus (Bloch). T3 injection in vivo (200 ng) in normal fish decreased the
      lipid peroxidation products and increased superoxide dismutase (SOD), catalase
      and glutathione peroxidase (GPx) activities after 30 min. T3 in vitro (10(-6) M)
      increased the antioxidant activities of catalase, glutathione reductase (GR), GPx
      and glutathione level after 15/30 min, except SOD, substantiating in vivo effects
      in normal fish. The results suggest a rapid regulatory effect of thyroid hormone
      in vivo and in vitro, in the removal of reactive oxygen species in A testudineus.

PMID- 16955761
TI  - Effect of endosulfan on growth, alpha amylase activity and plasmids amplification
      in Bacillus subtilis.
AB  - Endosulfan, a chlorinated hydrocarbon insecticide of cyclodiene subgroup acts as
      a contact poison in a wide variety of organisms. In the present study, the effect
      of endosulfan on the growth, alpha amylase activity and plasmid amplification was
      investigated in Bacillus subtilis system. The bacteria were grown in medium,
      incubated with different concentrations (32, 48, 64 and 80 microg/mL) of
      endosulfan. The bacterial growth was gradually seen after 1st day at up to 48
      microg/L endosulfan. The 48 microg/L endosulfan inhibited approximately 50% of
      the bacterial growth. No growth was observed at and after 64 microg/L endosulfan,
      for all days (1-5). Also, no alpha amylase activity was found in the supernatant
      of the culture medium containing 64 and 80 microg/L endosulfan, whereas slight
      activity was observed with 32 and 48 microg/L endosulfan concentration. The
      amount of plasmid increased up to 50% in the presence of 32 microg/L endosulfan.
      Endosulfan had no effect on the alpha amylase activity in vitro.

PMID- 16955762
TI  - Periorbita: computed tomography and magnetic resonance imaging findings.
AB  - PURPOSE: The periorbita has been regarded as the critical structure in decision
      of exenteration in the patients with paranasal (PNS) malignancies. The purpose of
      this study is to present the CT and MRI findings of the periorbita with PNS
      malignancies. MATERIALS AND METHODS: Ten patients with PNS cancers were chosen
      for this study. PNS CT and MRI scans were performed on all patients. The imaging
      findings were reviewed retrospectively by consensus of two neuroradiologists.
      Assessment of the defect of the orbital bone and invasion of the orbital fat was
      made by CT and MRI. The signal intensity (SI), thickness, enhancement, and
      correlation with the orbital bone of the periorbita were analyzed on MRI. The
      intraoperative and pathologic reports were used as the gold standard for orbital
      invasion. RESULTS: In patients with bone defects, it was impossible to
      differentiate the periorbita from the mass on CT. The periorbita showed
      hypointensity on T2-weighted images compared with the SI of mass. On Gd-enhanced
      T1-weighted images, the periorbita showed less enhancement than the mass in nine
      patients. Six patients showed two hypointense layers (the outer bony wall and the
      inner periorbita) between the mass and orbital fat on T2-weighted images. The
      thickness of the periorbita was 0.79-1.4 millimeter. Orbital invasion was more
      conspicuous on T2-weighted coronal images than on the CT images. CONCLUSIONS: MRI
      was more conspicuous for detecting orbital invasion than CT. The mass beyond the
      thickened periorbita on T2-weighted images was considered to be a positive
      finding of orbital invasion.

PMID- 16955763
TI  - Correlation between fiberoptic nasal endoscopy and acoustic rhinometry in adults
      without nasal complaints.
AB  - BACKGROUND: Acoustic rhinometry indirectly calculates cross-sectional areas of
      the nose at various locations from the nostrils and the total volume of the nasal
      cavity. These parameters are calculated from an area-distance curve displayed by
      the device. METHODS: Seventy-seven adults between the ages of 20 and 40 years who
      had no nasal complaints were examined by acoustic rhinometry and fiberoptic nasal
      endoscopy in an attempt to compare and correlate areas of nasal narrowing
      detected by these two methods. RESULTS: The comparison between the distances to
      the various narrowed areas revealed a statistically significant correlation
      between the first three constrictions detected by acoustic rhinometry and the
      first three areas of anatomic narrowing measured by fiberoptic nasal endoscopy in
      both nares but no correlation between the fourth constriction and the fourth
      measurement on either side. CONCLUSION: The results confirm an anatomic
      correlation between the two examination methods, identifying the first
      constriction as the nasal valve, the second constriction as the head of the
      inferior nasal turbinate, and the third constriction as the head of the middle
      turbinate. The fourth constriction did not correspond to the choanal region.

PMID- 16955764
TI  - Nasal airflow during respiratory cycle.
AB  - BACKGROUND: Knowledge on the airflow patterns in the nasal cavity is essential to
      understanding the function of the nasal cavity. This study has attempted to
      observe the breath cycle of nasal airflow during respiration at rest. METHODS: We
      constructed a nasal cavity model by rapid prototyping using 1.25-mm-thick CT data
      and devised a piston pump driven by a cam, to simulate respiration at rest. The
      airflow was evaluated with particle image velocimetry and visualized in coronal
      reconstructed images. RESULTS: During the inspiration, a maximal velocity was
      observed at the valve area and the main stream occurred in the middle and
      superior airways. During the expiration, main stream was noted in the middle
      airway and was slow compared with the flow during inspiration. Vortexes were
      observed between inspiration and expiration. CONCLUSION: This result widens our
      knowledge of nasal airflow and this technique will allow a more physiological
      understanding of nasal operations.

PMID- 16955765
TI  - Nasal airway measurements in children treated by rapid maxillary expansion.
AB  - BACKGROUND: Rapid maxillary expansion is an orthodontic procedure that is
      commonly used to widen the maxilla. It is generally admitted that this technique
      is effective to correct palate narrowing, whereas there has not been agreement on
      the effect of this procedure in nasal parameters. The availability of a reliable
      and objective technique to assess the geometry of nasal cavities, such as
      acoustic rhinometry, stimulated the present investigation. METHODS: Twenty-seven
      children, undergoing rapid maxillary expansion, were evaluated by rhinomanometry
      and acoustic rhinometry. Postero-anterior radiographs were taken in 15 patients
      for cephalometric measurements. Examinations were performed before expansion
      treatment and after 12 month follow-up and compared to the measurements obtained
      from an untreated control group. RESULTS: With regard to rhinomanometry, we
      recorded a significant reduction in nasal airway resistance (NAR) after the
      orthodontic procedure only in decongestion. Using acoustic rhinometry, we found a
      significant increase in total minimum cross-sectional areas (TMCA) and total
      nasal volume (TNV) after the expansion both in basal and decongested conditions.
      Also, nasal cavity width and interzygomatic distance had a significant mean
      increase after the treatment. Comparison of measures between the control group
      and the treated group showed that the increase in TMCA and TNV, as well as the
      decrease in NAR, were significantly greater in the treated group in both basal
      and decongested conditions. CONCLUSION: We demonstrated that rapid maxillary
      expansion is an effective procedure in widening nasal cavities with respect to an
      untreated control group and that the reported improvement in nasal breathing
      after palatal expansion, is a consequence of an increase in nasal size.

PMID- 16955766
TI  - Studies on the effects of ice collars on nasal blood volume using optical
      rhinometry.
AB  - BACKGROUND: The possible benefit of ice collars for treatment of nosebleed is
      controversial. The aim of this study was to investigate changes of nasal blood
      volume before and after application of ice collars to the neck. Nasal blood
      volume was investigated using optical rhinometry. METHODS: A total of 15 young,
      healthy volunteers participated. After ice collars were placed on the neck area
      of the subjects, changes in the blood volume of the nose were measured by means
      of optical rhinometry for the whole nose, but also regionally at the nasal septum
      (Kiesselbach's area). After baseline measurements over 1 minute, the ice collar
      was applied. Optical rhinometric measurements were performed continuously.
      RESULTS: Although the ice collar showed no effect on the blood volume of the
      whole nose, there was a significant decrease in blood volume (p < 0.01) at the
      septum. CONCLUSION: Application of ice collars to the neck area of the subjects
      is followed by a decrease in blood volume of Kiesselbach's area, which may
      provide the basis for the clinical observation that ice collars are helpful in
      the treatment of nosebleeds.

PMID- 16955767
TI  - A prospective randomized blinded cross-over trial using nasal drops in patients
      with nasal polyposis: an evaluation of effectiveness and comfort level of two
      head positions.
AB  - BACKGROUND: The aim of this study was to compare the efficacy and the degree of
      discomfort caused by the Mygind's (supine and head extended) position and the
      lying on the side head down (LSHD) position used for instilling nasal drops. We
      performed a prospective randomized blinded cross-over trial. METHODS: Twenty
      three patients with nasal polyps were recruited and were given Betnesol nasal
      drops for 6 weeks after assessing their peak nasal inspiratory flow rate and
      grading the polyps. The assessor was blinded to the position used by the patient
      that was selected randomly. The patients were reviewed after 6 weeks when both
      their flow rates and their polyp grades were reassessed. They were given a visual
      analog chart to record the ease by which drops could be instilled and any
      discomfort caused by the position. After a 2-week washout period the patients
      were treated for another 6 weeks with the same drops using the other head
      position. RESULTS: Twenty-one patients completed the study. The LSHD and Mygind's
      positions were equally effective in controlling the nasal polypi. Mygind's
      position was easier to instill drops in the nose although LSHD position caused
      less discomfort for the patient. The nasal peak inspiratory flow increased
      linearly as the polyp size decreased. In 86 and 90% of the patients the nasal
      obstruction and nasal discharge, respectively, were well controlled. CONCLUSION:
      The drops were efficacious in both head positions. The LSHD position caused the
      least discomfort, although patients found Mygind's position easier to instill
      drops. Steroid nasal drops are an effective way to manage patients with nasal
      polyposis.

PMID- 16955768
TI  - Endoscopic transphenoidal pituitary surgery with real-time intraoperative
      magnetic resonance imaging.
AB  - BACKGROUND: The aim of this study was to report and show the technique, results,
      and complications of combined endoscopic and intraoperative magnetic resonance
      imaging (IMRI) surgical treatment of pituitary disease from both a technical and
      a surgical perspective. METHODS: We performed a retrospective chart review of 10
      endoscopic, endonasal resections of 10 pituitary macroadenomas using the Polestar
      N-10 IMRI system in a tertiary health care facility. The patient demographics,
      tumor measurements, and postoperative symptoms and complications were assessed.
      The effect of the magnetic field on the video screen, the image quality of the
      IMRI images, and IMRI detection of residual tumor were evaluated also. RESULTS:
      IMRI images were obtained in all cases and were of sufficiently high quality to
      indicate adequate decompression of the optic chiasm and the removal of all
      suprasellar tumor. However, there was significant distortion of the video monitor
      regardless of the viewing angle. This was overcome with a wall-mounted plasma
      screen. Residual tumor was found with IMRI and resected endoscopically in three
      cases. In two other cases, suspected residual tumor on IMRI was examined
      endoscopically and found to be a normal postoperative change. In two cases no
      tumor was seen on the IMRI. Five patients who had preoperative progressive visual
      loss preoperatively improved postresection and two patients who had increased
      insulin growth factor 1 preoperatively normalized postoperatively. No delayed
      cerebrospinal fluid leaks or any other complications occurred. CONCLUSION:
      Combining intraoperative endoscopy and IMRI is an effective surgical modality for
      pituitary surgery. Each technology provides complimentary information, which can
      assist the surgeon in safely maximizing the extent of resection.

PMID- 16955769
TI  - Image guidance: A survey of attitudes and use.
AB  - BACKGROUND: The aim of this study was to determine access to, usage of, and
      attitudes toward image guidance in endoscopic sinus and anterior skull base
      surgery. METHODS: We performed a survey of American Rhinologic Society members.
      RESULTS: Of 1050 surveys mailed, 340 (32.4%) were returned and scored. Image
      guidance was available to 86% of respondents. Eighteen percent of respondents did
      not use image guidance in any cases, and 25% used it in up to 10% of cases. Eight
      percent of respondents used image guidance in >90% of cases. Respondents felt the
      primary indication for this technology is in revision or advanced cases. Seventy
      percent of respondents felt image guidance was not typically indicated for a
      primary total ethmoidectomy and >90% of respondents felt it was either a relative
      or absolute indication for revision frontal sinus exploration, modified Lothrop
      procedure, or closure of cerebrospinal fluid leak. Attitudes of the respondents
      did not vary by year of residency completion or by the use of image guidance
      during residency. Current access to image guidance was associated with a higher
      likelihood of feeling it was indicated. CONCLUSION: The majority of respondents
      had access to image guidance. Many feel it is a relative or absolute indication
      for revision and advanced endoscopic sinus and skull base procedures. A very
      small minority used this technology in all cases. The results of this survey
      reflect the opinion of the respondents. They do not necessarily reflect the views
      of the American Rhinologic Society or of practicing otolaryngologists in general.

PMID- 16955770
TI  - Surgical management of lesions of the sphenoid lateral recess.
AB  - BACKGROUND: Pneumatization of the sphenoid sinus occasionally includes an
      extensive lateral recess creating an area beneath the temporal lobe that is
      relatively inaccessible to surgical intervention. Pathology in this anatomic
      location presents special surgical and therapeutic challenges. Recently, several
      authors have described the endoscopic transpterygopalatine fossa approach to this
      anatomic region. This approach is associated with minimal morbidity while
      providing direct endoscopic surgical access for managing a variety of disease
      processes in this region. METHODS: This study presents eight cases requiring this
      approach or a modification of this approach. Six patients presented with temporal
      lobe meningoencephaloceles with cerebrospinal fluid rhinorrhea. Each case was
      managed successfully through this surgical approach. RESULTS: One patient
      experienced transient postoperative palatal anesthesia due to injury to the
      greater palatine nerve and another complained of ipsilateral dry eye
      postoperatively. Two other patients had neoplasms (inverting papilloma and
      chondrosarcoma), which were successfully addressed through this technique. There
      were no postoperative complications in these patients. CONCLUSION: We have
      previously described the relationships of neural and vascular structures in this
      anatomic region. This article will review these relationships as they pertain to
      this surgical approach and will discuss the indications, techniques, and surgical
      outcomes in this series of patients. This approach is a valuable addition to the
      endoscopic armamentarium of the experienced endoscopic surgeon.

PMID- 16955771
TI  - Gauze-assisted technique in endoscopic removal of fungus balls of the maxillary
      sinus.
AB  - BACKGROUND: The aim of this study was to establish and evaluate a newly developed
      gauze-assisted technique in complete removal of fungus balls of the maxillary
      sinus with usual instruments of endoscopic sinus surgery. METHODS: Fifteen adults
      with fungus balls of the maxillary sinus were collected. A newly developed
      surgical technique that involves the replacement of the fungus balls with the
      gauze strip was applied. The number of course and duration of this procedure were
      recorded. RESULTS: The fungal material was removed with less than two courses of
      this procedure in these patients. The duration of this procedure ranged from 2 to
      5 minutes with an average of 4 minutes. Postoperatively, these patients had been
      followed for 16-50 months with an average of 29 months. Neither recurrence nor
      complication was noted. CONCLUSION: With the excellent results, we strongly
      suggest this easy and timesaving technique in the management of such patients.

PMID- 16955772
TI  - Treatment of epistaxis in hereditary hemorrhagic telangiectasia patients by argon
      plasma coagulation with local anesthesia.
AB  - BACKGROUND: Recurrent epistaxis is the most common manifestation of hereditary
      hemorrhagic telangiectasia (HHT). The aim of this study was to determine the role
      and efficacy of argon plasma coagulation (APC) in the management of epistaxis
      caused by HHT. METHODS: From 1997 to 2004, 43 patients with diagnosed HHT were
      treated for recurrent epistaxis with APC in our department. RESULTS: Thirty-six
      patients reported substantial reduction of bleeding after treatment. Of the 18
      patients who previously needed blood transfusions, 13 reported substantial
      reduction of bleeding after treatment and no blood transfusions were necessary.
      CONCLUSION: APC allows a control of epistaxis in HHT patients and guarantees a
      long time free from blood transfusions. This treatment modality can be performed
      with local anesthesia, is not invasive, is well tolerated, is inexpensive, and
      can be used as a first step even in patients who need to undergo several blood
      transfusions for their epistaxis.

PMID- 16955773
TI  - Endoscopic sinus surgery for the treatment of vascular tumors.
AB  - BACKGROUND: This study points out the effectiveness of the endoscopic approach
      for the treatment of vascular lesions such as angiofibroma, hemangioma, and
      hemangiopericytoma involving the nose and paranasal sinuses. METHODS: We
      performed a retrospective study at an academic tertiary referral center. Thirteen
      patients, diagnosed with vascular tumors of the nose and paranasal sinuses were
      treated endoscopically between February 1996 and July 2003. All patients
      underwent endonasal endoscopic surgery. Preoperative angiography with
      embolization was performed in all but two cases. RESULTS: The follow-up of this
      series varied from 6 to 75 months (mean, 23 months); only one recurrence (8%) was
      observed in the juvenile angiofibroma group encountered 20 months
      postoperatively. This recurrence was again treated endoscopically. The average
      intraoperative blood loss for the removal of the juvenile angiofibroma group was
      300 mL and it was 100 mL for the other vascular tumors. CONCLUSION: Endoscopic
      treatment alone is an effective approach for the removal of selected cases of
      vascular tumors. Even in the presence of a lesion with limited intracranial
      extension, the tumor still may be amenable to an endoscopic approach alone. On
      the contrary, this is not true if the intracranial extension receives feeding
      vessels from the internal carotid arterial system.

PMID- 16955774
TI  - Changes in nasal resonance after functional endoscopic sinus surgery.
AB  - BACKGROUND: Hyponasality may be present in patients with chronic rhinosinusitis
      because of decreased resonance of nasal cavities. Nasalance is a parameter of
      nasality measured by a nasometer. This study investigated the influence of
      functional endoscopic sinus surgery (FESS) on nasalance and determined the
      correlation of the nasalance change with nasal volume change. METHODS: When
      patients with chronic rhinosinusitis underwent FESS, nasalance was measured by
      nasometry and nasal volume was measured by acoustic rhinometry before and at
      least 6 months after surgery. RESULTS: There were 81 eligible patients enrolled
      in the study. Nasalance scores and nasal volumes were significantly increased
      after FESS. The increased nasalance value was moderately correlated with the
      increased midnasal and postnasal volumes. The correlation between postoperative
      changes in nasalance scores and nasal volumes was more remarkable in patients
      without nasal polyps than in those with nasal polyps and it was also higher in
      patients with allergic rhinitis than in those without allergic rhinitis.
      CONCLUSION: This study showed that the FESS effectively increased nasalance
      scores and nasal volumes in patients with chronic rhinosinusitis, but the
      increase in nasalance scores did not appear to be achieved largely through the
      increased nasal volumes.

PMID- 16955775
TI  - Outcome of endoscopic sinus surgery in children with allergic rhinitis.
AB  - BACKGROUND: Allergic rhinitis (AR) is a morbid condition in children with chronic
      rhinosinusitis. The study goal was to determine whether children with AR who are
      undergoing endoscopic sinus surgery (ESS) will have a poor outcome. METHODS: The
      study population consisted of 141 patients who underwent ESS between January 1994
      and December 2002. The outcome of ESS was measured at least 1 year after the
      operation. RESULTS: The overall success rate was 80%. Children with an allergy
      had 77% success rate compared with children with no allergy who had an 84%
      success rate (p = 0.25). Children with AR who were on treatment before surgery
      had an 84% success rate compared with 62% for those children with AR but were not
      treated (p = 0.022). CONCLUSION: ESS in children with AR does not have a poorer
      outcome. Treatment of the allergy before surgery may improve the success of ESS.

PMID- 16955776
TI  - Epidermoids of the paranasal sinuses and beyond: endoscopic management.
AB  - BACKGROUND: Epidermoid tumors of the craniofacial skeleton are uncommon, with the
      exception of acquired cholesteatoma of the temporal bone. These lesions may be
      primary embryologic in origin or, less frequently, may be iatrogenic or
      posttraumatic. METHODS: We report three cases of unusually encountered
      epidermoids, all of which were managed by endoscopic marsupialization via
      paranasal sinus approaches. We also review the pathophysiology and clinical
      presentation of these rare entities. RESULTS: The first patient is a 60-year-old
      man with a congenital epidermoid of the petrous apex removed via an endoscopic
      transsphenoid approach assisted by image-guided surgical navigation with CT/MRA
      merge. The second case is a 48-year-old woman with a history of trauma found to
      have a mass in the pterygopalatine space. An endoscopic transmaxillary approach
      was used to ligate the internal maxillary artery and marsupialize the cyst into
      the maxillary sinus. The third patient is a 22-year-old woman with a supraorbital
      ethmoid epidermoid tumor discovered intraoperatively during surgery for a
      presumed mucocele. This patient also had a known history of trauma. The cyst was
      marsupialized into the adjacent frontal sinus. Image-guided surgical navigation
      using CT was performed in the latter two cases. All patients are free of
      recurrence with follow-up ranging from 14 to 26 months. CONCLUSION: With
      advancements in endoscopic techniques, including the use of image guidance, many
      of these relatively uncommon lesions can be managed by minimally invasive
      approaches via the paranasal sinuses.

PMID- 16955777
TI  - Pattern of inflammation and impact of Staphylococcus aureus enterotoxins in nasal
      polyps from southern China.
AB  - BACKGROUND: This study analyzes the impact of Staphylococcus aureus enterotoxins
      (SAEs) and the inflammatory pattern in polyps from China. METHODS: Nasal tissue
      was obtained from 27 consecutive bilateral nasal polyps and 15 control patients
      and assayed for eotaxin, interleukin-5, soluble interleukin-2 receptor,
      transforming growth factor (TGF) beta, myeloperoxidase, eosinophil cationic
      protein, total IgE, and specific IgE to SAEs. Activated eosinophils were stained
      using EG2 antibodies in polyps from Chinese and comparative white patients.
      RESULTS: The number of EG2+ eosinophils was significantly lower in polyps from
      Chinese patients versus white patients. Chinese polyps showed significantly
      increased IgE and soluble interleukin-2 receptor versus control samples, whereas
      TGF-beta1 was significantly decreased. Ten of 27 samples in the polyp group
      versus 0 of 15 controls contained SAE-IgE (p < 0.01). TGF-beta1 was significantly
      down-regulated in SAE+ samples versus SAE- samples (p = 0.04). CONCLUSION: Nasal
      polyps from China are characterized by B- and T-cell activation, a minor
      eosinophilic inflammation compared with polyps from white subjects, and a
      decrease in TGF-beta1 in comparison with control inferior turbinate tissue. One
      third of patients with polyps showed an IgE response to SAEs.

PMID- 16955778
TI  - Superantigens and chronic rhinosinusitis II: analysis of T-cell receptor V beta
      domains in nasal polyps.
AB  - BACKGROUND: The superantigen (SAg) hypothesis of chronic rhinosinusitis (CRS)
      suggests that toxins within the nose stimulate massive oligoclonal expansion of T
      cell populations with subsequent eosinophil recruitment and tissue inflammation.
      SAgs are capable of activating 1 x 10(4) more lymphocytes than conventional
      antigens by binding specific Vbeta-domains of the T-cell receptor (TCR). The net
      effect is skewing from the normal Vbeta-profile by oligoclonal expansion of
      specific domains. This study will assess polyp tissue for evidence of an SAg
      response in CRS with nasal polyps (CRSwNP). METHODS: This study consists of a
      prospective analysis of 18 CRSwNP subjects undergoing sinus surgery. Flow
      cytometry was used to analyze the distribution of 24 specific TCR V beta-domains
      in lymphocytes from polyp tissue and blood. Evidence of oligoclonal expansion was
      tabulated for each specimen and defined as mean normative percentage + 2 SD.
      RESULTS: Eighteen of 18 CRSwNP subjects showed expansion of polyp lymphocytes
      expressing TCRs with specific V beta-domains. The average number of V beta-clones
      per CRSwNP subject was seven in polyp lymphocytes but only two in blood
      lymphocytes. CONCLUSION: The current results indicate that polyp lymphocytes
      exhibit significant oligoclonal expansion of specific V beta-domains. These data
      are considered diagnostic of a SAg effect. The corresponding blood profile is
      much less, suggesting that the nose is the primary source of stimulus. Although
      the trigger(s) for this expansion are unknown, these data are consistent with the
      hypothesis that staphylococcal toxins are central to the development of CRSwNP.

PMID- 16955779
TI  - Eicosanoid metabolism and eosinophilic inflammation in nasal polyp patients with
      immune response to Staphylococcus aureus enterotoxins.
AB  - BACKGROUND: Staphylococcus aureus-derived enterotoxins (SEs) have been implicated
      in the pathogenesis of airway inflammatory diseases, especially nasal polyposis.
      However, the exact role of these molecules in the regulation of eicosanoid
      synthesis in this pathology remains unexplored. We studied the possible impact of
      SE-induced immune responses on the eicosanoid production in nasal polyp (NP)
      patients. METHODS: Tissue sample homogenates from NP patients, with (NP-SEs[+])
      and without detectable IgE-antibodies to SEs (NP-SEs[-]; ImmunoCap system), were
      assayed for IL-5, myeloperoxidase, leukotriene CJD4/E4 (LTC4/D4/E4), LTB4,
      lipoxin A4, total IgE, and eosinophil cationic protein. RESULTS: Inflammatory
      makers, eicosanoids, and total IgE were significantly increased in NP-SEs(+)
      compared with NP-SEs(-) tissues, with the exception of myeloperoxidase, which was
      similar in both groups. Eicosanoid concentrations correlated to IL-5 and
      eosinophil cationic protein; however, only cys-leukotriene levels correlated with
      IgE-antibodies to SEs, independently of allergy and asthma. CONCLUSION:
      Eicosanoid synthesis is up-regulated in polyp tissue of patients with immune
      response to SEs and seems to be related to the inflammatory reaction induced by
      these enterotoxins.

PMID- 16955780
TI  - Immunolocalization of surfactant protein A and D in sinonasal mucosa.
AB  - BACKGROUND: Surfactant-associated proteins (SP) A and D are in the family of
      collectin proteins that play an integral part in the innate defense system. SP-A
      and SP-D expression and function are altered in a variety of inflammatory and
      infectious diseases of the lungs, such as asthma, allergies, and cystic fibrosis.
      Our prior studies are the first to identify the presence of these proteins in the
      human sinonasal cavity. The objective of this study was to immunolocalize SP-A
      and SP-D in human sinonasal tissue. METHODS: Sinonasal mucosal biopsies were
      performed in patients with various forms of chronic hyperplastic rhinosinusitis
      with nasal polyposis and nondiseased mucosa from patients undergoing
      transsphenoidal hypophysectomy. (n = 10) Immunolocalization of surfactant
      proteins was performed with antibodies to SP-A and SP-D using immunoperoxidase
      staining technique. Isotype-negative controls were performed on all specimens.
      RESULTS: Analyses of mucosal biopsy specimens from human sinonasal tissue reveals
      staining within respiratory and intermediate (metaplastic)-type surface
      epithelium. In addition, staining was intense in the submucosal ductal epithelium
      of the seromucinous glands. These properties appear to be consistent regardless
      of disease state and location within the sinuses. CONCLUSION: This is the first
      study to immunolocalize SP-A and SP-D in sinonasal human mucosa. These are
      secreted proteins that are intricately involved in innate immunity in the lungs.
      Their secretion in the upper airway indicates that future studies may allow
      manipulation of these proteins and development of novel treatments for sinonasal
      pathology.

PMID- 16955781
TI  - Molecular profile of the antrochoanal polyp: up-regulation of basic fibroblast
      growth factor and transforming growth factor beta in maxillary sinus mucosa.
AB  - BACKGROUND: Various pathogenetic mechanisms have been proposed to explain the
      development of antrochoanal polyps (ACPs); however, the cause is still largely
      unknown. The aim of this study was to characterize the expression and the
      potential role of a battery of molecular markers in the development of ACPs. A
      prospective controlled study of a case series was performed. METHODS: Tissue
      samples of maxillary sinus mucosa were obtained from 14 patients with ACPs, 17
      patients with chronic nonpolypoid maxillary sinusitis, and 4 patients with normal
      maxillary sinus mucosa; RNAs were extracted from the sinus mucosa, and
      semiquantitative reverse transcription-polymerase chain reaction was performed
      for basic fibroblast growth factor, transforming growth factor P, and mucin genes
      (MUC), MUC5AC, MUC5B, and MUC8, to investigate their expression. RESULTS: The
      expression of basic fibroblast growth factor and transforming growth factor beta
      was significantly higher in ACPs than in chronic rhinosinusitis and healthy
      mucosa. Meanwhile, the levels of expression of MUC genes were higher in ACPs and
      chronic rhinosinusitis compared with healthy mucosa. CONCLUSION: These findings
      suggest that ACPs may represent an inflammatory reaction caused by overproduction
      of tissue-derived growth factors in an inductive environment.

PMID- 16955782
TI  - Inflammatory pathway gene expression in chronic rhinosinusitis.
AB  - BACKGROUND: The main objective in this preliminary experiment was to compare gene
      expression in the sinus mucosa of patients with chronic hyperplastic
      rhinosinusitis (CRS) against normal subjects, using gene microarray technology.
      The specific aim was to examine alterations in inflammatory mediator expression
      in patients with CRS. We performed a prospective experimental study. METHODS:
      Total RNA samples were obtained from the sinus mucosa biopsies of 14 patients
      with chronic hyperplastic sinusitis and 4 normal controls, using the Affymetrix
      recommended protocol. The data for 22,000 genes on the GeneChip U133A were
      generated from 18 hybridizations. Affymetrix GeneChip 5.0 was used as the image
      acquisition software for the U133A chips. Data normalization, log transformation,
      statistical analysis, and pattern study were performed with GeneSpring software.
      Comparison between patients with CRS and normal controls were performed using the
      Welch t-test, with log transformed data. RESULTS: There were a total of 1283
      genes scored as differentially expressed between groups. The value of p, the
      probability of a false positive, was set to <0.05. Hierarchical clustering was
      applied to study coexpression patterns of the 1283 significant genes. The
      inflammatory pathway was overlaid with the differential expressed gene list. Four
      genes involved in the inflammatory pathway, interleukin (IL)-6, IL-12A, IL-13,
      and tumor necrosis factor (TNF) alpha (2) were consistently overexpressed in
      patients with hyperplastic CRS. CONCLUSION: There is overexpression of four major
      genes of the inflammatory pathway (IL-6, IL-12A, IL-13, and TNF-alpha (2)) in
      patients with CRS compared with the normal population. Defining gene expression
      profiles may help elucidate new key factors in the pathogenesis of CRS and
      perhaps aid in the development of new therapeutic modalities.

PMID- 16955783
TI  - Impaired norepinephrine-mediated contraction of isolated nasal mucosa in guinea
      pigs with allergic rhinitis.
AB  - BACKGROUND: One of the causes of nasal obstruction associated with allergic
      rhinitis probably is caused by the dilatation of plexus cavernosum in nasal
      mucosa. In this study, the change in vascular responsiveness of nasal mucosa was
      investigated in the septal mucosae isolated from guinea pigs with allergic
      rhinitis. METHODS: An allergic rhinitis model was prepared in guinea pigs by
      repeated challenge with aerosolized dinitrophenylated-ovalbumin antigen. Twenty
      four hours after the last antigen challenge, the changes in the isometrical
      tension of isolated nasal septal mucosa were measured. RESULTS: In isolated nasal
      mucosal tissues, both norepinephrine (NE) and leukotriene D4 caused concentration
      dependent contractile and relaxant responses, respectively. The NE-induced
      contractile response was significantly attenuated in nasal mucosae of the
      repeatedly antigen challenged guinea pigs. The mucosal relaxation induced by
      leukotriene D4 was slightly attenuated in this animal model of allergic rhinitis.
      CONCLUSION: This study shows an attenuation of NE-induced contraction of isolated
      nasal mucosa in the antigen-exposed guinea pigs. The impaired contractile
      response mediated by sympathetic alpha-adrenoceptors of nasal blood vessels might
      be involved in the development of nasal obstruction in allergic rhinitis.

PMID- 16955784
TI  - Lobular capillary hemangioma of the nasal cavity: A retrospective study on 40
      patients.
AB  - BACKGROUND: Nasal lobular capillary hemangioma (LCH) is a benign lesion of
      unknown etiology that must be included in the differential diagnosis of vascular
      lesions. Based on a large cohort of LCH patients, we retrospectively analyzed the
      clinical presentation, histological and radiological findings, and the treatment
      strategy. METHODS: Clinical records of 40 patients affected by LCH, treated in a
      20-year period at two university hospitals, were reviewed. Data concerning
      symptoms, possible etiologic factors, endoscopic findings, imaging studies, and
      treatment were collected. RESULTS: Previous nasal trauma and pregnancy were
      identified as possible causes in six (15%) and two (5%) patients, respectively.
      The main symptoms were unilateral epistaxis (95%) and nasal obstruction (35%).
      Lesions ranged in size from 1 to 8 cm and mainly involved the nasal septum (45%)
      and the nasal vestibule (17.5%). In the four (10%) patients with a large lesion,
      radiological evaluation was helpful not only in assessing the extent, but also in
      suggesting the possible nature of the lesion. All patients underwent endoscopic
      resection under local (72.5%) or general (27.5%) anesthesia. At mean follow-up
      time of 53 months, no recurrence has been observed. CONCLUSION: To the best of
      our knowledge, this is the largest series of patients with nasal LCH. When the
      mass is considerable in size, differentiation from other hypervascularized
      lesions may be intriguing. Under these circumstances, information obtained with
      imaging may sometimes suggest a correct diagnosis without resorting to biopsy.
      Endoscopic surgery is the treatment of choice even for large lesions, that do not
      require preoperative embolization.

PMID- 16955785
TI  - Severe chemotherapy-induced parosmia.
AB  - BACKGROUND: Smell and taste disorders are among the side effects of chemo- and
      radiotherapy. Although direct radionecrosis of the salivary glands and the taste
      buds might explain the chemosensory problems after radiotherapy, the olfactory
      and gustatory complaints seen after chemotherapy remain unexplained. The patients
      reporting olfactory symptoms rarely complain about qualitative olfactory
      disorders such as parosmia or phantosmia. Quantitative olfactory loss such as
      anosmia and hyposmia seem to be more frequent. METHODS: We present the case of a
      63-year-old woman with chemotherapy-induced parosmia leading to severe nutrition
      and appetite problems resulting in a life-threatening weight loss. RESULTS: With
      the aid of a simple nose clip the parosmia could be abolished and oral food
      intake became possible again. Parosmia resolved gradually over an observation
      period of 9 months, in parallel to an increase of olfactory sensitivity. The
      patient progressively gained appetite and weight. CONCLUSION: Parosmia can occur
      as a severe and potentially life-threatening complication of chemotherapy. This
      rare presentation of parosmia illustrates the importance of olfactory testing
      with an adequate recognition of the underlying problem and a consecutive
      treatment.

PMID- 16955786
TI  - [The expression of estrogen receptor alpha and beta in the intervention of
      different estrogens in rat bone metabolism].
AB  - In this present study, female rats were ovariectomized (OVX) as the models of
      osteoporosis. The aim is to determine the different mechanisms of estrogen
      receptor(ER) alpha and beta pathway in mediating estrogen to participate in
      trabecular bone metabolism, and to further explore the distinction of modulation
      on ER alpha or ER beta between estrogens with different components. Mature female
      Sprague-Dawley rats (n=40) were randomly divided into four groups: group Control
      (sham operated), group OVX (only ovariectomized), group CEE (OVX rats treated
      with conjugated equine estrogens) and group EV (OVX rats treated with estradiol
      valerate). Sham operation and OVX were performed 48 days (12 estrums) before
      different liquid diet. The rats in group Control and group OVX were orally
      administrated with physiological saline solution and the rats in group CEE or
      group EV were orally administrated with CEE or EV for 12 days (3 estrums) before
      sacrifice. Relative quantitative reverse transcription- polymerase chain reaction
      (RT-PCR) and western blot techniques were utilized to compare the levels of ER
      alpha and ER beta mRNA and proteins in trabecular bone among groups. The results
      showed that in rat trabecular bone of group Control, the expression of ER alpha
      protein (1.433 +/- 0.250) was significantly higher than that of ER beta(0.687 +/-
      0.120), whereas the ER alpha mRNA (0.285 +/- 0.033) was much lower than ERbeta
      mRNA(0.590 +/- 0.044). Following OVX, the levels of ER alpha protein (0.685 +/-
      0.103) declined significantly, whereas mRNA levels (0.405 +/- 0.036) markedly
      increased. Both the protein (1.091 +/- 0.078) and mRNA (0.729 +/- 0.030) levels
      of ER beta significantly increased after OVX. After treatment with CEE, the
      expression of ER beta protein (0.583 +/- 0.129) and mRNA (0.618 +/- 0.043) were
      markedly down-regulated compared with group OVX. After treatment with EV, the ER
      alpha protein expression (1.272 +/- 0.247) was markedly up-regulated, while ERa
      mRNA (0.277 +/- 0.040) and ER beta protein (0.620 +/- 0.174) were markedly down
      regulated compared with group OVX. On the other hand, the loss of bone mass in
      rat trabecular bone by OVX (0.192 +/- 0.010) was markedly gained after CEE (0.228
      +/- 0.012) and EV (0.259 +/- 0.007) treatment. These results demonstrate that
      ERalpha may be the predominant subtype expressed in female rat trebecular bone
      and play a key role in the bone metabolism. This study also shows that estrogens
      with different components protect bone through variant ERs pathway.

PMID- 16955787
TI  - [Enhancing the induced immune responses of Lagurus lagurus zona pellucida 3 DNA
      vaccine by molecular adjuvant C3d].
AB  - To investigate the enhancement of Lagurus lagurus zona pellucida 3 gene (lzp3)
      immunization induced by molecular adjuvant C3d in comparison with plasmid pcDNA3
      LZP3 (pcD-L) in non-C3d fused form, the eukaryotic expression vector pcDNA3-LZP3
      C3d3 (pcD-LC) including lzp3 and three copies of C3d in fusion form was
      constructed. In vitro,RT-PCR and Western blot showed that lzp3 mRNA and protein
      were expressed in HeLa cells transfected with pcD-L and pcD-LC, respectively. In
      vivo,the result of ELISA showed that NIH female mice vaccined with pcD-LC
      elicited higher titer, longer lasting anti-LZP3 antibody than non-C3d fused form
      pcD-L (P<0.05) by intramuscular gene immunization. MTT analysis indicated that
      the lymphocytes proliferation response of the pcD-LC primed mice was
      significantly stronger than that of the blank plasmid injected mice.
      Antifertility experiment showed that pcD-LC had enhanced effect on blocking
      fertility of mice (P<0.05) with no disruption of follicular development. These
      results proved that C3d enhanced immune responses induced by lzp3 vaccine and
      antifertility effect,and provided the basis for the future study of the Lagurus
      lagurus reproductive controlling.

PMID- 16955788
TI  - [Caspase-3 antisense oligodeoxynucleotides inhibit caspase-3 expression and
      apoptosis of gamma-irradiated HL-60 cells].
AB  - It has been shown that gamma -irradiation induces apoptosis of the human
      promyeloid leukemia cell line HL-60, but the mechanism remains unclear. To
      explore the effect of caspase-3 in this apoptotic model, antisense
      oligodeoxynucleotides (ASODNs) targeting 5'-noncoding region (ASODN-1) and
      initial translation region (ASODN-2) of caspase-3 mRNA were designed, synthesized
      and introduced into HL-60 cells by means of liposome-mediated transfection
      followed by gamma-irradiation in the present study. The TUNEL assay was used for
      morphological analysis of HL-60 cell apoptosis. Immunocytochemical staining,
      Western blotting and RT-PCR were, respectively, performed for detecting
      expression of caspase-3 and its mRNA. HL-60 cells transfected with mismatched
      oligodeoxynucleotide (MODN) or untransfected were taken as the control groups.
      The TUNEL assay showed that the percentages of HL-60 cell apoptosis induced by
      gamma-Irradiation in both ASODN-1 and ASODN-2 groups were significantly reduced
      compared with those in the control group (P<0.01) when the final transfection
      concentration was > or = 3 micromol/L. Immunocytochemistry demonstrated that in
      the ASODN-1 and ASODN-2 groups, caspase-3 positive cell percentages were reduced
      and average gray values of the positive cells increased significantly compared
      with those in the control group (P<0.01). Western blotting found that procaspase
      3 expression in HL-60 cells of the ASODNs groups was decreased,and it was lower
      in the ASODN-1 group than in the ASODN-2 group. RT-PCR revealed marked expression
      of caspase-3 mRNA in HL-60 cells of the control group. Expression of caspase-3
      mRNA was decreased after ASODNs transfection. Furthermore, ASODN-1 was more
      effective in inhibiting HL-60 cell apoptosis (P<0.05) and caspase-3 expression
      (P<0.01) than ASODN-2. These results indicate that caspase-3 mRNA ASODNs prevent
      HL-60 cells from apoptosis induced by gamma-radiation,and reduce expression of
      caspase-3 and its mRNA. These effects are dose dependent in a certain range.

PMID- 16955789
TI  - [ATPase distribution in fertile and sterile anther of a genic male sterile
      Chinese cabbage].
AB  - Lead precipitation technique was used to locate Adenosine Triphosphatase (ATPase)
      in the fertile and sterile anthers of a genic male sterile Chinese cabbage
      (Brassica campestris L. ssp. Chinensis Makino var. communis Tsen et Lee),which
      would help us to understand the relationship between ATPase and sterility of
      anthers of the cabbage. At megaspore mother cell (MMC) of fertile anther many
      ATPase reactive precipitates were located in nucleus but few of the precipitates
      in cytoplasm of the cell. Meantime, some ATPase reactive precipitates also
      specially appeared in mitochondria of the MMC. After meiosis of MMC, the
      precipitates in cytoplasm of early microspores increased evidently and then
      decreased step by step with development. The ATPase reactive precipitates in
      tapetal cell also increased ultimately in early microspore stage and then
      decreased with development of anther. When microspore formed a large vacuole,
      which is late stage of microspore, the ATPase reactive precipitates were located
      in its mitochondria. After microspores mitosis a few of the ATPase reactive
      precipitates appeared in pollen grains and tapetal cells. More ATPase reactive
      precipitates appear in MMC of sterile anther than in fertile anther but fewer of
      them in mitochondria. Although more ATPase granules appear in abnormal tetrad
      microspores which degenerate by cytoplasm shrinkage and plasmolysis. The relation
      between ATPase and male sterility of the cabbage was discussed.

PMID- 16955790
TI  - [Relation between the decline of photosynthetic function and H2O2 accumulation in
      leaf life span of tobacco].
AB  - Correlations among H2O2 accumulation, chloroplast photosynthetic function decline
      and H2O2-scavenging enzymes of AsA-GSH cycle in leaf life span of tobacco
      (Nicotiana tabacum L. cv NC89) were studied. Photosynthetic rate displayed
      elevated phase,active photosynthesis duration and sharp fall phase while the
      chlorophyll content displayed elevated phase,relative steady phase and sharp fall
      phase during leaf life span. The decline of photosynthetic parameters was slow
      first and then sharp,and the decline of ribulose 1,5-bisphosphate carboxylase
      (RuBPCase) activity was obviously faster than that of photosynthetic electron
      transport activity during the decline of photosynthetic function. The decline of
      photosynthetic function was divided into reversible decline and irreversible
      decline. Ascorbate peroxidase (APX) and Glutathione reductase (GR) remained
      higher level in reversible decline stage,while declined fast in irreversible
      decline stage. H2O2 content was significantly negative correlated with
      chlorophyll content, photosynthetic rate, RuBPCase activity,APX and GR activity
      during the decline of photosynthetic function in tobacco leaves. Localized
      staining of H2O2 stated that the decline of photosynthetic function was closely
      correlative with H2O2 accumulation. The decline of photosynthetic function in
      tobacco leaves was faster than the decline of AsA-GSH cycle function.

PMID- 16955791
TI  - [Preliminary study on expression of oviductin in mouse cervix].
AB  - In the present study,in order to investigate the pattern of the expression and
      location of oviductin using RT-PCR and Western blot,a 410bp cDNA fragment was
      amplified from mouse cervix tissue. Sequencing analysis and homology comparison
      with BLAST alignment showed that this fragment amplified from mouse cervix was
      homologous to the region from +310 to +714 of the mouse OGP gene in Genebank by
      the degree up to 100%. Western blot showed 60 KD and 30 KD components from mouse
      cervix same as those from mouse oviduct mucosa epithelium. Semi-quantitative RT
      PCR analysis showed that expression of OGP was significantly higher at the
      estrous stage than that of non-estrous stage and almost no expression in the
      immature mouse. Those results suggest that the mRNA level of mouse cervix
      oviductin was related to estrous cycle,implied with estrogen-dependence. To
      further confirm the results,in situ hybridization histochemistry analysis showed
      that OGP mRNA was expressed at columnar epithelium of mouse cervix. To clarify
      the possible significance of oviductin expressed at the cervix, the function of
      oviductin on the mobility of human sperm was studied using "loss-of-function".
      The VAP, VCL, ALH, VSL showed no significant differences of the mobility of the
      human sperm in the conditioned medium blocked by the anti-CTP rOGP (rabbit
      Oviductin) antiserum compared with that in the conditioned medium of the normal
      rabbit serum. These results suggest that rOGP may not affect the mobility of
      human sperm in vitro.

PMID- 16955792
TI  - [Morphological and anatomical characterization of a stripe mutant with abnormal
      floral organs in rice].
AB  - A rice double mutant was derived from the transgenic process,but it does not
      carry the alien gene. The mutant showed white stripe on stem, leaf and spikelet.
      In some growing stage,the leaf started to produce fork or curliness. The floret
      number increased, showing multi-lemma/palea, palea-like or lemma-like lodicules
      or enlarged lodicules, additional pistil and stamen and the spited floret. With
      observation of cell ultra structure using electron microscope,the white tissue
      showed concaved cell wall and abnormal plastid which could not develop normal
      lamellae and thylakoid. The contents of chlorophyll and net photosynthesis rate
      in the mutant were obviously lower than those in the wild type. The cells in
      green sectors grow normally with the exception of the bigger cell volume. The
      morphogenesis of floral organ was observed by using the scanning electron
      microscopy (SEM). Results showed that the stamen development was not synchronal
      and the sizes of stamen primordium were different in mutant, and the carpel was
      smaller than that of wild type.

PMID- 16955793
TI  - [Cadmium-induced cytotoxicity and intracellular Ca2+ alteration in hepatocytes
      and protection by selenium].
AB  - Cadmium (Cd)-induced cytotoxicity and intracellular Ca2+ alteration ([Ca2+]i) in
      hepatocytes and intervention with selenium (Se) were studied to discuss mechanism
      of Cd-induced hepatocyte injury and protective effect by Se. Freshly primary
      culture hepatocytes isolated from neonatal mice were randomly divided into a
      normal control group, four treatment groups with cadmium chloride
      (CdCl2,5,25,100,250 micromol/L, respectively), two treatment groups with sodium
      selenite (Na2SeO3,10,20 micromol/L, respectively), and eight treatment groups
      with CdCl2 (5,25,100, 250 micromol/L,respectively) of administered Na2SeO3 (10,20
      micromol/L, respectively). Hepatocyte viability and its malondialdehyde (MDA)
      content as well as lactate dehydrogenase (LDH) activity in cultured medium were
      assayed, and the intracellular free Ca2+ level ([Ca2+]i) in hepatocytes was
      detected with laser scanning confocal microscope (LSCM) at 12 h after treatment.
      The results showed that hepatocyte viability significantly decreased in Cd
      exposed groups with dosages, and had no significant differences in Se-treated
      groups compared with that of control group. Administration of Se increased or
      obviously raised the viability in Cd-exposed hepatocytes. We observed a dose
      dependent increase of LDH activity and significantly higher values in cultured
      medium of 100 and 250 micromol/L CdC12 groups compared with that in control
      group,while Se-treated groups had no significant change. LDH activity of
      administered Se in 25,100,250 micromol/L CdCl2 groups decreased or significant
      decreased, respectively. Different dosages of Cd induced significant elevation of
      MDA concentration in hepatocytes, but administration of Se to hepatocytes is
      incapable of eliciting the same consequences as Cd. 10 and 20 micromol/L Na2SeO3
      inhibited or significantly reduced MDA production in hepatocytes induced by
      25,100 and 250 micromol/L CdCl2, respectively. [Ca2+]i fluorescence intensity was
      significantly higher in Cd-exposed hepatocytes than in control cells and showed a
      dose-dependent manner,however, [Ca2+]i level of administered Se in hepatocytes
      was not enhanced and near to that of control cells. [Ca2+]i level of administered
      Se in Cd-exposed hepatocytes greatly decreased compared with Cd-exposed cells and
      significantly lower values of administered Se in 25 micromol/L CdCl2-exposed
      hepatocytes were observed and near to that of control cells. These results
      suggest that Cd induce cytotoxicity and damage as well as [Ca2+]i elevation in
      hepatocytes. Se can relieve the process of cytotoxicity and damage by intervening
      lipid peroxidation,improving and protecting [Ca2+]i homeostasis in Cd-induced
      hepatocytes.

PMID- 16955794
TI  - [The migration and differentiation of subventricular zone neural stem cells
      transplanted into the adult striatum].
AB  - Adeno-associated virus vectors (type2) containing the marker gene--green
      fluorescent protein (AAV2-GFP) were used to transduce subventricular zone neural
      stem cells (NSCs). NSCs labelled by gene product--GFP were transplanted into
      adult Sprague-Dawley rat striatum. The animals were allowed to survive for 45
      days, 90 days and 120 days before they were perfused. All the fixed brains were
      serially sectioned in the saggital plane,at the sickness of 30 microm with a
      cryostat microtome. These results showed that, at all stages, GFP labelled NSCs
      were seen in the injection sites,and a lot of them dispersed in the host brains.
      GFP labelled NSCs showed directional migration 45 days following transplantation.
      120 days after transplantation, a group of GFP labelled NSCs migrated dorsally
      and posteriorly, reached corpus callosum; another group of transplanted NSCs
      migrated ventrally and posteriorly,reached substantia nigra, moreover,a number of
      these cells migrated through or over the substantia nigra and reached the more
      ventral boundary of the substantia nigra. The migrating NSCs were in chains, GFP
      labelled cells in substantia nigra were beta-tubulin III immunoreactive.

PMID- 16955795
TI  - [DHEA inhibits apoptosis of murine OB through MAPK signaling pathways independent
      of either ARs or ERs].
AB  - Dehydroepiandrosterone (DHEA) is a promising agent for the treatment of post
      menopausal osteoporosis (PMO), but the molecular mechanisms and signaling
      pathways by which this steroid modulates apoptosis of osteoblasts (OB) are still
      poorly understood. In this study,the OBs were cultured in vitro by the enzyme
      digested method,treated with DHEA (10(-7) mol/L) for 0h, 24h, 48h, 72h,
      respectively. The expressions of ER alpha, ER beta and AR mRNA in OB were
      analyzed by RT-PCR. After the primary OBs were deprived of serum for a further
      24h, and then pretreated with 1 micromol/L ICI 182,780 (an estrogen receptor
      antagonist), 10 micromol/L Flutamide (an androgen receptor antagonist) or 100
      micromol/L U0126 (a specific inhibitor of MAPK pathway) for 1h, they were treated
      with a series of concentrations of DHEA (10(-10) - 10(-5) mol/L) in serum-free
      medium for 72h,the apoptotic cells were analyzed by FCM with the Annexin-V
      FITC/PI dual labeling technique. The OBs were incubated in 1 micromol/L ICI
      182,780 or 10 micromol/L Flutamide for 25 minutes,and then treated with different
      concentrations of DHEA for the further 10 minutes. The phosphorylation status of
      ERK1/2 was analyzed by Western blot. After the OBs were incubated with DHEA (10(
      7)mol/L) for 24h, 48h or 72h, respectively, its ERbeta and AR mRNA level were
      increased (P<0.05, P<0.01, respectively), but the ER alpha mRNA level had no
      change. The 10(-9) - 10(-6) mol/L of DHEA inhibited OBs early apoptosis induced
      by the serum deprivation (P<0.05, P<0.01, respectively). The inhibiting effect,
      moreover, could be blocked by the specific inhibitor of MAPK pathway, U0126. The
      effects of DHEA were neither blocked by the steroid hormone antagonist ICI
      182,780 nor by Flutamide. Western blot showed that neither receptor antagonist
      ICI 182,780 nor Flutamide could block the DHEA-induced ERKs phosphorylation in
      OBs,which was similar to the apoptosis. DHEA inhibits apoptosis in OBs presumably
      via a DHEA-specific receptor that involves mitogen activated protein kinase
      (MAPK) signal pathway, phospho-pERK1/2, independent of either ARs or ERs.

PMID- 16955796
TI  - Study on increasing expression of adrenomedullin in diabetic rats' retinal
      pigment epithelium cells.
AB  - To explore the possible involvement of adrenomedullin (AM)in the pathophysiology
      of diabetic retinopathy, we employed streptozotocin (STZ)-induced diabetic rats
      to study the alteration of the AM expression in the retinal pigment epithelium
      (RPE) cells of diabetic and normal rats by immunohistochemistry. The weight,
      blood sugar and urine sugar were also measured before and after model induction
      in both groups. The data of weight, blood sugar and urine sugar indicated no
      significant difference between the two groups before animal model induction. Four
      weeks after the induction of diabetes,the differences between the control and the
      diabetic group in weight,blood sugar and urine sugar were distinct (P<0.01). When
      compared with the normal retina, a significant increase of AM expression was
      observed in the diabetic rat' RPE cells,as shown by increased optical density and
      immunohistochemistry positive cell number(P<0.01). Our study provides
      experimental evidence that up-regulation of AM expression in retina of
      streptozotocin-induced diabetic rats under hyperglycemia condition.
      Adrenomedullin may play a role in the pathophysiology of diabetic retinopathy.

PMID- 16955797
TI  - [In vivo transduction of EGFP into female mouse reproductive system by
      electroporation and microbubble-enhanced sonoporation].
AB  - In the present study, the efficiency of in vivo transduction of EGFP plasmid DNA
      into adult female mouse reproductive system by means of electroporation and
      microbubble-enhanced sonoporation are discussed. In the first experiment,EGFP
      plasmid DNA was injected into the ovary and following electroporation (square
      electric pulses were applied five times at 60V with a constant time of 20ms).
      Green fluorescence was detected 10h after transduction. In the second experiment,
      plasmid DNA was mixed with the microbubble at different ratio and injected into
      the uterus and the ovary separately. The tissues were exposed to different
      combined ultrasound parameters immediately after injection. We found that the
      suitable parameter was 2 w/cm2 intensity, 20% duty cycle and 5min. Under this
      condition, green fluorescence was expressed in the uterus endometrium and ovarian
      cortex 12 h post-sonoporation and the expression lasted up to 5 days.

PMID- 16955798
TI  - [Morphological studies on direct regeneration of floral buds from in vitro
      cultures of sepal segments in Sinningia speciosa hiern].
AB  - The morphological changes in the cultures of sepal segments in Sinningia speciosa
      Hiern were observed with Zeiss Stemi 2000-C Stereomicroscope from 0 to 65 days
      after culture in vitro. The light yellow globular protuberances were observed on
      the cut edge and the surface of sepal segments after culture for 24 days. Then
      the globular protuberances grew bigger gradually. A lot of floral buds on the
      surface of sepal segments formed after culture for 60 days. The morphological
      changes in the cultures of sepal segments were studied with light microscopy
      after culture for 0 to 30 days as well. The cells of tissues of sepal segments
      arranged regularly and no dividing cell was observed on the first day culture.
      There appeared some small meristematic centers of dividing cells on cut edge and
      the lower epidermis on the 7th day after culture. To the 20th day culture in
      vitro, the floral organ primordia were differentiated on the cut edge. On the
      30th day culture, floral buds with petal, stamen primordia were observed. In
      addition, the morphological changes in the cultures of sepal segment were studied
      during the 14 to 30 days culture with scanning microscopy as well.

PMID- 16955799
TI  - Determining authorship. Deciding on authorship: giving credit where it is due
      (and only where it is due).

PMID- 16955800
TI  - Review of Pododermatitis circumscripta (ulceration of the sole) in dairy cows.
AB  - Sole ulcers are among the most frequent causes of lameness in dairy cattle. They
      are found most commonly in the hind lateral claw, are frequently bilateral, and
      have a high rate of reoccurrence. The pathogenesis of sole ulceration is
      primarily based on mechanical injury by the 3rd phalanx to the corium, basement
      membrane, and basal layers of the sole epidermis as a result of failure of the
      suspensory apparatus in the claw. The main pathways in the failure of the
      suspensory system include inflammatory (dermal vascular changes followed by
      disruption of keratinocyte proliferation and differentiation caused by local and
      systemic mediators) and noninflammatory (hormonal and biochemical changes in the
      peripartum period resulting in alterations of connective tissue in the suspensory
      system) pathways. Sole ulcers tend to occur in specific locations; the most
      reported site is the junction of the axial heel and sole. Other locations include
      the apex of the toe and the heel. Varying degrees of lameness may result, and the
      most severe are seen with complicated cases in which ascending infection affects
      the deeper structures of the claw. Pathologic changes at the ulcer site include
      dyskeratosis and dilated horn tubules with microcracks. Vascular changes include
      dilatation and thrombosis of capillaries with "neocapillary formation." Areas of
      dyskeratosis may remain for as long as 50 days at the ulcer site. Treatment
      includes corrective trimming and relief of weight bearing. Complicated cases may
      require surgical intervention.

PMID- 16955801
TI  - Effect of storage of reconstituted recombinant human thyroid-stimulating hormone
      (rhTSH) on thyroid-stimulating hormone (TSH) response testing in euthyroid dogs.
AB  - Bovine thyrotropin (bTSH) stimulation testing has long been considered the gold
      standard for diagnosis of canine hypothyroidism. Unfortunately, bTSH is no longer
      commercially available. Recently, the use of recombinant human thyrotropin
      (rhTSH) to perform thyroid-stimulating hormone (TSH) stimulation testing in dogs
      was described. The cost of an rhTSH vial (1.1 mg) limits the practical use of
      this product. The study reported here was performed to determine the effects of
      storing rhTSH on the post-TSH increase of serum total (TT4) and free (FT4)
      thyroxine concentrations during TSH stimulation testing in 12 euthyroid Beagles
      in a crossover trial. Three TSH tests with recombinant human thyrotropin (rhTSH;
      91.5 microg IV) were performed on each dog during 3 different periods: 1 with
      freshly reconstituted rhTSH (fresh); 1 with rhTSH, reconstituted and stored at 4
      degrees C for 4 weeks (refrigerated); and 1 with rhTSH, reconstituted and frozen
      at -20 degrees C for 8 weeks (frozen). Blood samples for determination of TT4 and
      FT4 concentrations were collected before and 4 and 6 hours after rhTSH
      administration. There was no significant difference in TT4 or FT4 concentration
      after stimulation with fresh, refrigerated, and frozen rhTSH. Furthermore, there
      was no significant difference between TT4 or FT4 serum concentration observed 4
      and 6 hours after rhTSH administration. In conclusion, reconstituted rhTSH can be
      stored at 4 degrees C for 4 weeks and at -20 degrees C for 8 weeks without loss
      of biological activity, allowing clinicians to perform more TSH response tests
      per vial.

PMID- 16955802
TI  - Lack of association between repeated vaccination and thyroiditis in laboratory
      Beagles.
AB  - BACKGROUND: Intensive vaccination protocols have been suggested as partially
      responsible for an increased prevalence of autoimmune diseases in dogs in recent
      years. The aim of this study was to determine whether repeated routine
      vaccination in dogs is associated with an increased prevalence of thyroiditis.
      METHODOLOGY/PRINCIPAL FINDINGS: We conducted a prospective experimental study
      with 20 healthy purpose-bred Beagles. Five dogs were vaccinated with a
      multivalent vaccine and a rabies vaccine. Five dogs received only the multivalent
      vaccine, and 5 dogs received only the rabies vaccine. Five dogs were unvaccinated
      controls. The multivalent vaccine was administered at 8, 10, 12, 16, 20, 26, and
      52 weeks of age and every 6 months thereafter. The rabies vaccine was
      administered at 16 and 52 weeks of age and then once a year. Blood samples were
      collected 1 week before euthanasia for evaluation of thyroid profiles and
      measurement of antibodies directed against canine thyroglobulin. Dogs were
      euthanized at 5.5 years of age, and the thyroid glands were evaluated
      histopathologically. Thyroiditis was present in 8 of 20 (40%) dogs at postmortem
      examination. No association was found between a dog being vaccinated and the
      prevalence of thyroiditis at postmortem examination. However, the power of the
      study to detect such an association was low because of the unexpected high
      prevalence of thyroiditis in the unvaccinated control dogs. Thyroid function
      tests were abnormal in 2 of 8 dogs with thyroiditis but were normal in all dogs
      without thyroiditis. CONCLUSIONS/SIGNIFICANCE: There was no evidence to support
      an association between routine vaccination and thyroiditis at postmortem
      examination in beagle dogs after repeated vaccination.

PMID- 16955803
TI  - Association of Helicobacter with cholangiohepatitis in cats.
AB  - Infection with Helicobacter spp. is increasingly linked with hepatobiliary
      inflammation and neoplasia in people and in a variety of animals. We sought to
      determine if Helicobacter species infection is associated with cholangiohepatitis
      in cats. Deoxyribonucleic acid was extracted from tissue blocks from cats with
      cholangiohepatitis (32), noninflammatory liver disease (13), and cats with normal
      liver histology (4). Deoxyribonucleic acid was polymerase chain reaction
      amplified with 2 sets of Helicobacter genus-specific primers, gel purified, and
      sequenced. Polymerase chain reaction-positive hepatic tissue was further examined
      with Steiner's stain, immunocytochemistry for Helicobacter species, and
      eubacterial fluorescent in situ hybridization. Gastric tissues of cats with known
      Helicobacter infection status served as controls for deoxyribonucleic acid
      extraction and sequence comparison. Helicobacter species were detected in 2/32
      cats with cholangiohepatitis, and 1/17 controls. Sequences had 100% identity with
      Helicobacter species liver, Helicobacter pylori, and Helicobacter
      fenelliae/cinaedii in a cat with suppurative cholangitis, Helicobacter species
      liver, Helicobacter pylori, and Helicobacter nemistrineae in a cat with mild
      lymphocytic portal hepatitis, and Helicobacter bilis in a cat with portosystemic
      vascular anomaly. In contrast, sequences from gastric biopsies showed highest
      homology (99-100%) to "Helicobacter heilmannii," Helicobacter bizzozeronii,
      Helicobacter felis, and Helicobacter salomonis. Fluorescent in situ hybridization
      revealed a semicurved bacterium, with Helicobacter-like morphology, in an
      intrahepatic bile duct of the cat with suppurative cholangitis. This study has
      identified Helicobacter deoxyribonucleic acid in 2/32 cats with
      cholangiohepatitis and 1/13 cats with noninflammatory liver disease.
      Deoxyribonucleic acid sequences of hepatic Helicobacter species were distinct
      from those found in the stomach and are broadly consistent with those identified
      in cat intestine and bile, and hepatobiliary disease in people and rodents.

PMID- 16955804
TI  - Dried solidified blood calculi in the urinary tract of cats.
AB  - We have noted an increased number of calculi submitted to the Gerald V. Ling
      Urinary Stone Analysis Laboratory, University of California, Davis, that do not
      contain crystalline material but appear to be composed of dried solidified blood
      (DSB). Canine and feline laboratory records from 1986-2003 were reviewed for
      samples composed of >99% DSB. No calculi from dogs were found, but specimens from
      49 cats were composed of >99% DSB, of which almost half (n = 22) had been
      submitted after 2001. The DSB calculi had been removed surgically or by
      postmortem examination from all areas of the upper and lower urinary tract. All
      samples were well formed and could be divided in half with Rongeur forceps.
      Detailed case information was available for 12 cats. Urinalyses were available
      for 9 of the 12 cats, and the mean specific gravity was 1.017 (range, 1.009
      1.032). Red blood cells were reported in the sediment of all cats, with most
      containing >100 RBC/hpf. Ureteral obstructions but no radio-opaque calculi were
      visible by radiography, including radiographic contrast studies. Reports of
      ultrasound examinations were available for 10 cats, and discrete calculi were not
      recorded. In addition to polarized light microscopy, infrared spectroscopy and
      electron probe microanalysis were performed on a subset (n = 6, DSB calculi; n =
      3, control calculi) of samples. Significantly more carbon, nitrogen, and sulfur
      (P = .012, P = .02, and P = .012, respectively) were present in the elemental
      analysis of the DSB calculi than in the control calculi, suggesting that the DSB
      calculi are primarily formed from organic material. At this time, we are
      uncertain why these DSB calculi become solidified, and we recommend that samples
      be submitted both in formalin and preservative free to further investigate their
      etiology.

PMID- 16955805
TI  - Temporal relationship between gastrointestinal protein loss, gastric ulceration
      or erosion, and strenuous exercise in racing Alaskan sled dogs.
AB  - BACKGROUND: Alterations in the appearance and function of gastrointestinal mucosa
      are common after strenuous exercise. However, the duration of exercise required
      to alter the gastrointestinal mucosa has not been reported. HYPOTHESIS: We used
      42 sled dogs to test the hypothesis that the magnitude of exercise-induced
      gastrointestinal mucosal dysfunction is related to exercise duration. ANIMALS:
      Six dogs served as conditioned controls, and the remaining dogs were randomly
      chosen for examination after 1-5 consecutive days of running at 100 miles/d.
      METHODS: Gastroduodenoscopy and measurement of gastric permeability were
      performed 24 hours after cessation of exercise. Intestinal protein loss
      (represented by fecal alpha-1 protease inhibitor concentration) was measured
      within 6 hours of cessation of exercise. Twelve of the 42 dogs were examined
      again after 5 months of detraining to determine the effect of training on
      gastrointestinal mucosal function. RESULTS: Exercise increased gastric
      permeability (P = .04) and endoscopic severity of gastric lesions (P < .0001),
      but neither variable was significantly affected by distance traveled. Acute
      exercise had no effect on intestinal protein loss. Untrained dogs had
      significantly lower fecal alpha-1 protease inhibitor concentrations compared with
      trained, unexercised dogs. Training had no effect on gastric permeability to
      sucrose or the endoscopic appearance of the stomach. CONCLUSIONS AND CLINICAL
      IMPORTANCE: These data suggest that relatively modest exercise is required to
      increase intestinal protein loss, but more substantial exercise is required to
      cause alterations in the proximal gastrointestinal tract. However, none of these
      alterations appear to progress with increasing exercise duration.

PMID- 16955806
TI  - Failure of imidocarb dipropionate to clear experimentally induced Ehrlichia canis
      infection in dogs.
AB  - The recommended treatment for canine ehrlichiosis is tetracycline or its analog
      doxycycline, although recent reports have documented ineffective clearing of
      Erchlichia canis after doxycycline administration. Imidocarb dipropionate is used
      as an alternative treatment to tetracycline or is used in conjunction with
      doxycycline. The effectiveness of imidocarb dipropionate in clearing Ehrlichia
      species from the blood and tissues of dogs with E. canis infection has not been
      thoroughly evaluated. Fifteen dogs were experimentally infected with E. canis.
      Ten dogs were treated with imidocarb dipropionate (6.6 mg/kg, IM, 2 injections
      given 2 weeks apart). Five infected control dogs were not treated. Blood samples
      from all 15 dogs were E. canis DNA positive by PCR assay by 3 weeks after
      inoculation (PI), and E. canis antibodies were detected by IFA assay by 1 week
      PI. Blood platelet counts in all dogs were below the reference interval by 4
      weeks PI. E. canis DNA was detected in bone marrow and splenic aspirates by PCR
      assay 4 weeks PI but not before infection. Bone marrow aspirates were E. canis
      DNA positive by PCR assay in 14/15 dogs, and splenic aspirates were E. canis DNA
      positive by PCR assay in 13/15 dogs. Blood samples from all treated and control
      dogs remained positive for E. canis DNA by PCR assay, and platelet counts
      remained below preinoculation values 13 weeks PI (6 weeks after 2nd treatment).
      As administered in this study, imidocarb dipropionate did not clear experimental
      E. canis infection in dogs.

PMID- 16955807
TI  - Liver disease in dogs with tracheal collapse.
AB  - BACKGROUND: Hepatopathy in dogs with chronic respiratory diseases is poorly
      recognized. The aim of this study was to evaluate liver parameters alanine
      transferase, alkaline phosphatase, and glutamate dehydrogenase, as well as basal
      and stimulated bile acid concentration, in dogs with tracheal collapse.
      HYPOTHESIS: Dogs with tracheal collapse have hepatopathy. ANIMALS: 26 dogs with
      tracheal collapse. MATERIALS AND METHODS: Gall bladder contraction was stimulated
      by intramuscular injection of a synthetic cholecystokinin analogue (ceruletide).
      Twelve healthy Beagle dogs and 30 dogs of various breeds investigated previously
      without evidence of hepatic, gastrointestinal, or respiratory diseases served as
      control. Amelioration of liver variables was assessed after stent implantation.
      RESULTS: Twelve of 26 (46%) dogs had increased serum activity of 2 or more liver
      enzymes. Serum basal bile acid concentrations were high in 24 of 26 dogs. Twenty-
      and 40-minute stimulated bile acids were significantly higher in dogs with
      tracheal collapse (64.2 +130.0/-43.0 micromol/L and 82.6 +164.0/-57.1 micromol/L)
      compared to the control dogs (7.0 +/- 3.6 micromol/L and 6.4 +/- 3.5 micromol/L).
      All twelve dogs reevaluated after a median of 58 days (48-219 days) had a normal
      breathing pattern and significantly decreased 20 and 40 minutes stimulated bile
      acids (50.0 +92.7/-32.8 micromol/L, 52.8 +97.6/-34.3 micromol/L; P = .0043),
      whereas plasma liver enzyme activities were not significantly influenced.
      CONCLUSION AND CLINICAL IMPORTANCE: There was a significant hepatic dysfunction
      in the majority of dogs with a tracheal collapse. Liver function should be
      routinely assessed in dogs with severe respiratory disease.

PMID- 16955808
TI  - Frequency and risk factors for urinary tract infection in cats with diabetes
      mellitus.
AB  - BACKGROUND: Identification and control of infections are important in the
      management of diabetic cats. Urinary tract infections have not been well
      characterized in diabetic cats. This retrospective study was performed to review
      and characterize urinary tract infections in diabetic cats. HYPOTHESIS: Urinary
      tract infections are common in diabetic cats. ANIMALS: A review was made of the
      medical records of 141 diabetic cats that had had urine obtained for culture by
      antepubic cystocentesis and that had not been treated with antibiotics, undergone
      urinary tract catheterization or urinary tract surgery within 2 weeks of urine
      collection or had urethral obstruction at the time of urine collection. METHODS:
      A review of medical records. RESULTS: Urinary tract infection was identified in
      18 of 141 diabetic cats. Escherichia coli was the most common isolate (67%).
      Female cats were at increased risk (prevalence odds ratios [POR], 3.7; 95%
      confidence interval [CI], 1.3 to 10.2; P = .013). Clinical signs of lower urinary
      tract disease and findings on urine sediment examination were good predictors of
      positive urine cultures. CONCLUSIONS AND CLINICAL IMPORTANCE: Urinary tract
      infections are common in diabetic cats regardless of status of diabetic control,
      suggesting routine monitoring with urine sediment exams or urine culture is
      warranted.

PMID- 16955809
TI  - Copper-associated chronic hepatitis in Labrador Retrievers.
AB  - This study summarizes the clinical and pathologic findings in 15 Labrador
      Retrievers with copper-associated chronic hepatitis (CACH). Our hypothesis was
      that this form of hepatitis is caused by a defect in hepatic copper metabolism,
      which most likely originates from a genetic defect. Affected Labradors consisted
      of 11 female and 4 male Labrador Retrievers. Eight family members of 2 of these
      patients were examined prospectively, as were 6 unrelated healthy Labrador
      Retrievers. All dogs were registered at the breed club. The average age at
      clinical presentation was 7 years (range, 2.5-10.5 years). All dogs were
      presented for anorexia, which was associated with vomiting in 8 patients. The
      diagnosis of CACH was based on histologic examination of liver biopsy specimens
      in all dogs, including semiquantitation of copper. A disproportionate increase in
      alanine aminotransferase (ALT) activity relative to alkaline phosphatase (ALP)
      activity, as well as the centrolobular localization of copper and the association
      of copper accumulation with hepatic lesions, suggested a primary copper storage
      disease rather than primary cholestatic liver disease causing copper
      accumulation. Mean hepatic copper concentration measured in related Labradors was
      1,317 microg/g dry weight liver (range, 402-2,576 microg/g). Mean hepatic copper
      concentration of unrelated normal Labradors was 233 microg/g dry weight liver
      (range, 120-304 microg/g). Our findings support the hypothesis that a hereditary
      form of hepatitis occurs in Labrador retrievers and is caused by a defect in
      hepatic copper metabolism.

PMID- 16955810
TI  - Prospective evaluation of the balloon-to-annulus ratio for valvuloplasty in the
      treatment of pulmonic stenosis in the dog.
AB  - BACKGROUND: In dogs, treatment of pulmonic valve stenosis (PS) with pulmonary
      balloon valvuloplasty (PBV) is a viable method to decrease the pressure gradient
      across the valve. However, to the authors' knowledge, the variables that
      influence the selection of the correct balloon size for the procedure have not
      been explored. Moreover, the lesions caused by the procedure have not been
      detailed. HYPOTHESIS: Variables that influence the measurement of the annulus
      could affect selection of the balloon size. We sought to determine the effects of
      treatment when the balloon-to-annulus ratio (BAR) was or > 1.3, but within the
      recommended range of 1.2-1.5, regardless of whether dilation was performed with
      single or double balloon technique. ANIMALS: Twenty-five Beagles with PS were
      studied. METHODS: Inter- and intra-observer variability, echocardiography versus
      angiocardiography, and systolic versus diastolic timing were evaluated for the
      BAR. Assessment of right ventricular (RV) pressure, Doppler gradient, stenotic
      valve area, and RV wall thickness were compared before and 1, 90, and 180 days
      after treatment. Postmortem examination of the heart was done. RESULTS:
      Significant correlations existed in measurement of the annulus; however,
      variation existed that would change balloon size. Improvement in the degree of PS
      was significant regardless of the BAR or single or double ballooning. In the most
      severely affected dogs, continued improvement was noted on day 90. Postmortem
      examination revealed tears in the commissures and the valve leaflets.
      CONCLUSIONS: Multiple factors influenced determination of the BAR and a range of
      1.2-1.5 was effective without detrimental consequences. Dogs with severe PS had
      continued decrease in RV pressure 3 months after treatment.

PMID- 16955811
TI  - Validation of 2 techniques for electrocardiographic recording in dogs and cats.
AB  - BACKGROUND: Standard electrocardiographic (ECG) recording in the dog and cat is
      commonly performed in right lateral recumbency, by connecting the ECG leads to
      the skin of the patient via metallic alligator clips. The jaws of the alligator
      clips are usually filed or flattened to reduce their uncomfortable pressure on
      the patient's skin. However, filed and flattened alligator clips can occasionally
      lose their grip to the skin, causing lead detachment during standard ECG
      recording. HYPOTHESIS: The aim of the study was to validate two novel ECG
      recording techniques ("gel" and "pads"). ANIMALS: Six-lead standard ECG recording
      was obtained from 42 dogs and 40 cats using the standard technique, as well as
      the two novel methods. METHODS: Measurements were taken of the amplitude and
      duration of P waves and QRS complexes, duration of PQ and QT intervals, and mean
      electrical axis (MEA). In each recording, five representative complexes were
      measured, and the results were averaged for each parameter. RESULTS: A good
      quality ECG recording was obtained with all the three different techniques,
      although a degree of wandering trace was observed in one third of cats with the
      "pads" technique. Bland-Altman analysis showed good agreement between the ECG
      values recorded with the two novel techniques and those recorded with the
      standard traditional technique. Furthermore, the observed differences were not
      clinically relevant, except for the R wave amplitude recorded with the "pads"
      method in cats (-0.35 to 0.37 mV). CONCLUSIONS AND CLINICAL IMPORTANCE: In
      conclusion, this study supports the reliability and clinical validity of the
      "gel" and "pads" techniques for ECG recording both in the dog and the cat, with
      some limitations for the "pads" technique in cats.

PMID- 16955812
TI  - Applications, complications, and outcomes of transvenous pacemaker implantation
      in 105 dogs (1997-2002).
AB  - We reviewed the indications for age and breeds of dogs who received transvenous
      endocardial artificial pacemaker (AP) implantation (n = 105) and complications
      and survival thereafter at a single institution over a 6-year period. A third
      degree atrioventricular (AV) block (59%) and sick sinus syndrome (SSS; 27%) were
      the most common indications, along with a high-grade second-degree AV block (9%)
      and atrial standstill (5%). The most common breeds identified were Labrador
      Retriever (n = 16; 11 with a third-degree AV block), American Cocker Spaniel (n =
      14; 10 with SSS), and Miniature Schnauzer (n = 13; all with SSS). Common
      presenting complaints were syncope (n = 66) and exercise intolerance or lethargy
      (n = 25). Half of the dogs (n = 52) had a history of acute onset of clinical
      signs (<2 weeks). Mean survival time for the 60 dogs who died during the study
      period was 2.2 years (range, 0.1-5.8 years). Major complications occurred in 13%
      of dogs and included lead displacement (n = 7), sensing problems that led to
      syncope (n = 3), infection at the pacemaker site (n = 1), bleeding (n = 1), and
      ventricular fibrillation during implantation (n = 1; successfully defibrillated).
      Minor complications occurred in 11 dogs (11%). The success rate of transvenous AP
      implantation was comparatively high (all dogs survived the first 48 hours), and
      the complication rate was comparatively low when compared with a previous
      multicenter study, most likely because of how commonly the procedure was
      performed and supervisory experience.

PMID- 16955813
TI  - Ultrasonographic assessment of regional radial and longitudinal systolic function
      in healthy awake dogs.
AB  - BACKGROUND: Strain (St) and strain rate (SR) imaging are new ultrasound
      modalities based on tissue Doppler imaging (TDI) that allow quantitative
      assessment of segmental myocardial contraction or stretching and rate of
      deformation, respectively. HYPOTHESIS: Regional peak systolic St and SR could
      allow repeatable and reproducible assessment of systolic function of the right
      (RVW) and left (LVFW) myocardial walls in dogs. ANIMALS: Six healthy Beagle dogs
      were used to determine the repeatability and reproducibility of regional peak
      systolic St and SR in the RVW and LVFW (Study 1). These variables were also
      assessed in 30 healthy dogs of several breeds (Study 2). METHODS: Longitudinal
      peak systolic St and SR were recorded in 2 segments (basal and apical) of the RVW
      and LVFW. Radial peak systolic St and SR of the LVFW were also assessed. RESULTS:
      All within- and most (7/10) between-day coefficients of variation were <15%.
      Absolute values of the longitudinal deformation indices were significantly higher
      (P < .001) in the RVW (St = -39.5 +/- 5.5% and SR = -5.2 +/- 0.8 s(-1) at the
      base; St = -36.3 +/- 4.3% and SR = -4.7 +/- 1.1 s(-1) at the apex) than in the
      LVFW. Absolute values were also higher for the radial (St = 62.9 +/- 10.4% and SR
      = 5.8 +/- 1.1 s(-1), P < .001) than for the longitudinal LFVW motions.
      CONCLUSIONS AND CLINICAL IMPORTANCE: St and SR imaging is a repeatable and
      reproducible method for assessing systolic myocardial function. The combination
      of these indices with conventional echocardiographic variables may be useful for
      screening canine myocardial diseases.

PMID- 16955814
TI  - Heart disease as a cause of death in insured Swedish dogs younger than 10 years
      of age.
AB  - BACKGROUND: Population-based information on disease occurrence is paramount in
      clinical decision making and in designing preventative measures, but such
      information is scarce. HYPOTHESIS: The risk of cardiac death is higher in certain
      breeds and mortality varies by age and sex. DOGS: Dogs that were life insured by
      an animal insurance company between 1995 and 2002. METHODS: The mortality pattern
      for heart disease in insured dogs up to 10 years of age was studied. The
      influences of sex, age, breed, month, and geographic location were investigated
      by means of incidence rates, proportions, and survival proportions. Cox
      proportional hazards regression was used to model time to heart disease. RESULTS:
      405,376 dogs contributed to a denominator of 1,431,933 dog-years at risk (DYAR)
      and 3,049 dogs had been assigned a cardiac-related diagnosis as cause of death.
      The cardiac-related mortality for dogs <10 years of age, was 21.3 deaths per
      10,000 DYAR. This mortality in males and females was 27.3 deaths and 15.4 deaths
      per 10,000 DYAR, respectively. Twelve of 54 breeds had a point estimate above the
      overall rate. The 3 breeds with the highest point estimates were: Irish
      Wolfhounds, Cavalier King Charles Spaniels, and Great Danes (rates of 356, 247,
      and 179 deaths per 10,000 DYAR, respectively). CONCLUSIONS AND CLINICAL
      IMPORTANCE: Breed, age, and sex affect cardiac mortality in certain breeds of
      dogs, but no effects of month and geographic location were identified. These
      findings can assist clinicians in establishing diagnoses, and can assist breeders
      in defining priorities for preventative measures.

PMID- 16955815
TI  - Echocardiographic assessment of the left ventricular outflow tract in the Boxer.
AB  - BACKGROUND: Soft, variable ejection murmurs are common in Boxers and are
      associated with increased left ventricular outflow tract (LVOT) ejection
      velocities. Whether these murmurs are physiologic or indicate mild aortic
      stenosis is controversial. Ejection velocity is impacted by LVOT area and
      ventricular stroke volume (SV), suggesting that these variables are pertinent to
      murmur development. HYPOTHESIS: Boxers with ejection murmurs have a smaller LVOT
      and equivalent SV indices, compared with values in dogs without murmurs. ANIMALS:
      Three age- and weight-matched groups of dogs--15 Boxers with soft ejection
      murmurs (group I); 15 Boxers without murmurs (group II); and 15 nonBoxer dogs
      without murmurs (group III)--were studied. METHODS: All dogs underwent 2
      dimensional and Doppler echocardiographic examinations. The LVOT size at multiple
      levels; LVOT ejection velocity, stroke distance, and SV index; and right
      ventricular SV index were determined and compared by analysis of variance.
      RESULTS: Indexed LVOT areas in Boxer groups were not different, but were
      significantly smaller than those of non-Boxer dogs. Ejection velocities and
      stroke distances were significantly different across all groups, with group I
      having the highest and group III having the lowest values. Doppler SV indices
      (ml/m2) for group-I versus group-II Boxers were 70 +/- 16(SD) versus 62 +/- 12
      for the LVOT (P = .27) and 58 +/- 12 versus 48 +/- 9 for the right ventricle (P =
      .14). CONCLUSIONS AND CLINICAL IMPORTANCE: These data suggest that a relatively
      smaller LVOT in Boxers predisposes them to increased ejection velocity and
      development of murmurs. The contribution of SV to the genesis of these often
      labile murmurs requires additional study.

PMID- 16955816
TI  - Doppler echocardiographic prediction of pulmonary hypertension in West Highland
      white terriers with chronic pulmonary disease.
AB  - BACKGROUND: Pulmonary hypertension (PH) is commonly diagnosed by Doppler
      echocardiography (DE) of tricuspid regurgitation (TR). However, TR may be absent
      or difficult to measure. HYPOTHESIS: Doppler-derived systolic time intervals of
      pulmonary artery (PA) flow may be used to predict PH in dogs. ANIMALS: Seventy
      three healthy dogs and 45 West Highland white terriers (WHWT) with interstitial
      pulmonary disease (IPD). METHODS: Echocardiographic studies, including
      determination of right ventricular acceleration time (AT), ejection time (ET),
      and AT : ET ratio; right ventricular shortening fraction (RV-SF); and TR
      velocity, were performed. Pulmonary hypertension was defined by TR >3.1 m/s.
      RESULTS: In healthy WHWT, AT (median, range) was 73 ms (53 to 104) and AT : ET
      was 0.40 (0.28 to 0.55). AT : ET was minimally affected by age (R2 = 0.04, 95%
      confidence interval [CI] 0.01-0.07, P < .001) but not by heart rate, body weight,
      or RV-SF. In all WHWT with TR, AT and AT : ET were inversely related to
      calculated systolic PA pressure (R2 = 0.52, 95% CI 0.42-0.62, P < .001 and R2 =
      0.36, 95% CI 0.29-0.42, P = .001). Clinical cutoffs to predict systolic PH were
      defined for AT (58 ms; sensitivity [Se] 88% and specificity [Sp] 80%) and AT : ET
      (0.31; Se 73% and Sp 87%). CONCLUSION AND CLINICAL IMPORTANCE: PH is common in
      WHWT with IPD. Analysis of right ventricular AT and AT : ET may be predictive of
      PH and should be particularly useful if TR is absent.

PMID- 16955817
TI  - Oral amiodarone therapy in dogs with atrial fibrillation.
AB  - The medical records of client-owned dogs in which amiodarone was used to manage
      atrial fibrillation (AF) were reviewed. Data analyzed included signalment,
      history of heart failure, presenting complaint, clinical diagnosis, prescription
      drug history, number of re-examinations, outcome, and laboratory analysis
      including serum biochemical analysis, CBC, and thyroid function testing. Specific
      data for amiodarone included loading and maintenance dose, duration of loading
      dose, adverse effects, and reason for decreasing dose or discontinuation of
      amiodarone therapy. Follow-up data for 17 dogs were included in the analysis.
      Various cardiac diseases including cardiomyopathy, valvular endocardiosis, and
      congenital heart disease were diagnosed in the dogs. Median loading and
      maintenance dosages of amiodarone were 16.5 and 9.0 mg/kg of body weight/d,
      respectively. A >20% decrease in heart rate was achieved in 13 dogs (76%).
      Conversion to sinus rhythm was achieved and maintained in 6 dogs (35%).
      Amiodarone was discontinued in 5 dogs, and the dose was decreased because of
      symptomatic bradycardia (n = 1), asymptomatic (n = 1) and symptomatic (n = 3)
      increases in hepatic enzyme activities, and for unknown reason (n = 1). On the
      basis of >20% decrease in heart rate in 76% of the dogs and conversion to sinus
      rhythm in 35%, it was concluded that amiodarone may be useful in managing AF in
      dogs. The use of amiodarone in the medical management of AF in dogs warrants
      further investigation.

PMID- 16955818
TI  - Daily controlled physiotherapy increases survival time in dogs with suspected
      degenerative myelopathy.
AB  - The purposes of the study reported here were to evaluate the signalment and
      clinical presentation in 50 dogs with degenerative myelopathy, to evaluate
      whether mean survival time was significantly affected by various means of
      physiotherapy performed in 22 dogs, and to determine whether neurologic status,
      anatomic localization, or age at onset had an influence on survival time in dogs
      that received physiotherapy. We found a significant (P < .05) breed
      predisposition for the German Shepherd Dog, Kuvasz, Hovawart, and Bernese
      Mountain Dog. Mean age at diagnosis was 9.1 years, and both sexes were affected
      equally. The anatomic localization of the lesion was spinal cord segment T3-L3 in
      56% (n = 28) and L3-S3 in 44% (n = 22) of the dogs. Animals that received
      intensive (n = 9) physiotherapy had longer (P < .05) survival time (mean 255
      days), compared with that for animals with moderate (n = 6; mean 130 days) or no
      (n = 7; mean 55 days) physiotherapy. In addition, our results indicate that
      affected dogs which received physiotherapy remained ambulatory longer than did
      animals that did not receive physical treatment.

PMID- 16955819
TI  - Recurrence rate, clinical outcome, and cellular proliferation indices as
      prognostic indicators after incomplete surgical excision of cutaneous grade II
      mast cell tumors: 28 dogs (1994-2002).
AB  - The objectives of this study were to determine local recurrence rate, clinical
      outcome, and prognostic value of the number of argyrophylic nucleolar organizer
      regions (AgNORs), presence of proliferating cell nuclear antigen (PCNA), and
      number of Ki-67-positive nuclei after incomplete surgical excision of canine
      cutaneous grade II mast cell tumors (MCTs). This retrospective study included 30
      MCTs in 28 dogs. Medical records were examined and follow-up information was
      obtained from owners and referring veterinarians. Only cases in which excision
      was incomplete and no anvcillary therapy (other than prednisone) for MCT was
      given were included. Paraffin-embedded tumor tissues were retrieved for AgNORs,
      PCNA, and Ki-67 staining. Median follow-up time was 811.5 days. Seven (23.3%)
      tumors recurred locally. Median time to local recurrence was not reached with a
      mean of 1,713 days. The estimated proportions of tumors that recurred locally at
      1, 2, and 5 years were 17.3, 22.1, and 33.3%, respectively. Eleven (39.3%) dogs
      developed MCTs at other cutaneous locations. Median progression-free survival was
      1,044 days. Median overall survival was 1,426 days. The combination of Ki-67 and
      PCNA scores was prognostic for local recurrence (P = .03) and development of
      local recurrence was prognostic for decreased overall survival (P = .04). Results
      suggest that a minority of incompletely excised MCTs recur. Therefore, ancillary
      local therapies may not always be necessary. However, local recurrence can
      negatively affect survival of the affected dogs. Cellular proliferation indices
      may indicate the likelihood of MCT recurrence after incomplete excision.

PMID- 16955820
TI  - Systemic hypertension in dogs with leishmaniasis: prevalence and clinical
      consequences.
AB  - A prospective study was performed (November 1998 to December 2003) to determine
      the prevalence of systemic hypertension (SH) in dogs with glomerular disease
      secondary to leishmaniasis. One hundred and five dogs with leishmaniasis were
      screened and staged for the presence of renal disease (RD) and SH. For the
      purpose of the study, RD was defined as serum creatinine concentration > or = 1.4
      mg/dL, a urine protein/creatinine ratio > or = 0.5, or both. SH was defined as a
      systolic blood pressure (SBP) > or =180 mm Hg or an SBP between 150 and 179 mm Hg
      in the presence of clinical manifestations of SH. Fifty-two (49.5%) of the dogs
      had some degree of RD, and 32 (61.5%) of these dogs were diagnosed with SH.
      Moreover, SH also was diagnosed in 3 dogs without RD. Left ventricular
      hypertrophy (LVH), estimated by echocardiography, was the most frequently
      observed systemic consequence of hypertension, being present in 32 (91.4%) of the
      hypertensive dogs. Echocardiographic abnormalities were not detected in any of
      the 33 dogs with leishmaniasis without RD, which were used as controls. Ocular
      consequences of SH were observed in only 2 (5.7%) of the dogs with hypertension.
      We conclude that SH is prevalent in dogs with RD secondary to leishmaniasis, not
      only in the more severe stages but also in the early course of the illness before
      azotemia becomes apparent. Canine leishmaniasis may be a useful natural model to
      study SH secondary to glomerular disease.

PMID- 16955821
TI  - Treatment of dogs with lymphoma using a 12-week, maintenance-free combination
      chemotherapy protocol.
AB  - BACKGROUND: Treatment of lymphoma in dogs by long-term chemotherapy has favorable
      results. However, the efficacy of short-term, maintenance-free treatment
      protocols on remission and survival times in dogs has not been determined.
      HYPOTHESIS: That treatment using a 12-week chemotherapy protocol would be
      associated with satisfactory treatment outcome in dogs with lymphoma. ANIMALS: 77
      dogs with histologically or cytologically confirmed diagnosis of lymphoma.
      METHODS: Prospective clinical trial in which dogs were treated with a 12-week
      chemotherapy protocol consisting of L-asparaginase, vincristine,
      cyclophosphamide, doxorubicin, and prednisolone. RESULTS: Complete remission rate
      was 76.3%. Multivariate logistic regression analysis revealed that clinical
      substage (P = .006) and immunophenotype (P = .003) had a significant influence on
      the likelihood of a dog achieving complete remission. Median duration of first
      complete remission was 243 days (range 19-1,191 days). The 6-month, 1-year, and 2
      year remission rates were 68%, 28%, and 16%, respectively. In the multivariate
      analysis of patient variables, immunophenotype (P = .022) revealed a significant
      influence on first remission duration. Toxicosis was mild with the exception of 1
      treatment-associated death. CONCLUSIONS AND CLINICAL IMPORTANCE: In this group of
      dogs the 12-week maintenance-free chemotherapy protocol was well tolerated and
      had satisfactory results.

PMID- 16955822
TI  - A retrospective study of the incidence and the classification of bone marrow
      disorders in the dog at a veterinary teaching hospital (1996-2004).
AB  - BACKGROUND: An 8-year retrospective study was conducted to evaluate the
      prevalence and the classification of canine bone marrow disorders in a clinical
      pathology service at a university referral hospital. ANIMALS: Dogs evaluated for
      bone marrow disorders at a veterinary teaching hospital. HYPOTHESIS: A better
      understanding of the spectrum and the prevalence of canine bone marrow disorders
      can be achieved with a multiyear retrospective study. METHODS: Bone marrow
      aspirate smears, core biopsy specimens, and case records from 717 dogs were
      reviewed. RESULTS: Bone marrow specimens were first categorized based on the
      presence or the absence of a primary bone marrow disorder. Nondysplastic and
      nonmalignant pathologic changes were placed into 14 subcategories. Frequently
      observed pathologic disorders included nonregenerative immune-mediated anemia,
      pure red cell aplasia, bone marrow necrosis, myelofibrosis, and hemophagocytic
      syndrome. Dysmyelopoiesis (n = 61) was subcategorized into myelodysplastic
      syndromes (n = 27), and congenital (n = 1) and secondary (n = 33)
      dysmyelopoiesis. One hundred twenty-six cases of neoplasia were divided into
      acute leukemia (n = 46), chronic leukemia (n = 7), stage 5 malignant lymphoma (n
      = 28), multiple myeloma (n = 25), malignant histiocytosis (n = 11), metastatic
      mast-cell tumor (n = 3), sarcoma (n = 5), and carcinoma (n = 1). CONCLUSIONS AND
      CLINICAL IMPORTANCE: This study provides a general indication of the spectrum and
      the prevalence of canine bone marrow disorders at a referral center in North
      America.

PMID- 16955823
TI  - Comparative aspects and clinical outcomes of canine renal hemangiosarcoma.
AB  - BACKGROUND: Hemangiosarcoma (HSA) is a common solid tumor of the spleen, heart,
      and skin of dogs. Renal HSA represents an uncommon anatomic variant, with little
      reported about its biologic behavior and clinical outcome. HYPOTHESIS: That renal
      HSA is associated with longer survival than other visceral forms of HSA. ANIMALS:
      14 dogs with renal HSA. METHODS: Medical records from 1999 to 2004 were searched
      for dogs with histopathologically confirmed renal HSA, and data relevant to
      clinical signs, treatments, and outcomes were abstracted. RESULTS: Clinical signs
      were nonspecific, and the median duration of clinical signs before diagnosis was
      60 days. Two dogs presented in cardiovascular collapse secondary to
      hemoperitoneum. Common hematologic and biochemical abnormalities were anemia
      (9/14), hematuria (7/14), and proteinuria (7/14). One dog had pulmonary
      metastasis at diagnosis. All dogs had evidence of a renal mass visualized by
      abdominal radiography (14/14), ultrasound (9/14), or both. All dogs underwent
      nephrectomy, and 4/14 dogs also received adjunctive chemotherapy. Median survival
      time of all dogs was 278 days (range 0-1,005 days), and dogs with hemoperitoneum
      had significantly shorter survival times than dogs without hemoperitoneum (62
      days versus 286 days, P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: These
      results indicate that hemoperitoneum and distant metastasis at diagnosis appear
      to occur less frequently in dogs with renal HSA compared with other visceral
      forms of HSA. Furthermore, dogs with renal HSA have protracted disease
      progression, with improved 1-year survival rates and longer median survival time
      compared to dogs with splenic, cardiac, and retroperitoneal HSA.

PMID- 16955824
TI  - Percutaneous lung biopsy in the horse: comparison of two instruments and repeated
      biopsy in horses with induced acute interstitial pneumopathy.
AB  - The aim of the study reported here was to compare complications of lung biopsy in
      horses and the quality of the lung specimens after biopsy using the manual Tru
      Cut biopsy needle (TC) and an automated biopsy needle (ABN). For experiment 1,
      lung biopsy was performed in 50 horses with one instrument on one side of the
      thorax, and then with the other instrument on the other side. Postmortem
      examination was performed in 20 of the 50 horses. Coughing was detected in 10 of
      50 horses and epistaxis was observed in 6 of the 50 horses. Endoscopy revealed
      bleeding into the airways in 16 of 49 horses and in 5 of 49 horses after biopsy
      with the TC or the ABN, respectively. Use of the ABN induced a significantly
      smaller amount of bleeding. Pneumothorax was detected by radiography in 1 of 50
      horses. Hematoma diameter determined in 7 of 20 horses at postmortem examination,
      was significantly larger after biopsy with the TC than with the ABN. The quality
      of the lung specimen was good. In experiment 2, complications after repeated and
      multiple lung biopsies in 6 horses were evaluated. Moderate epistaxis was
      observed on 13 of 104 occasions. Bleeding into the airways was detected at
      endoscopy on 41 of 104 occasions, and pneumothorax was detected during 4 of 104
      occasions. Complications such as hematoma at the biopsy site and bleeding into
      the airways were greater after biopsy with the TC than after use of the ABN. Lung
      biopsy specimens obtained with the ABN were fairly safe for the animal.

PMID- 16955825
TI  - Variations in equid SLC11A1 (NRAMP1) genes and associations with Rhodococcus equi
      pneumonia in horses.
AB  - Rhodococcus equi is an important intracellular pathogen of horses, most commonly
      causing chronic, suppurative bronchopneumonia in foals. Although most foals
      likely are exposed to environmental R. equi within the 1st few days of life, only
      some develop R. equi pneumonia, and the basis of differences in susceptibility
      among foals currently is unknown. In this study, we investigated solute carrier
      family 11 member 1 (SLC11A1) gene sequences in the 5' untranslated region, exon
      1, and a portion of intron 1 for variations in 3 equid species (horse, donkey,
      zebra) and compared variants within 3 independent horse breeding farms for
      associations with R. equi pneumonia by use of an age-matched case-control design.
      Seven novel variants in the 5'untranslated region were identified as specific for
      one or both of the non-horse equid species sampled. In addition, a single novel
      horse variant in the 5'untranslated region, -57C/T, was identified in 4 breeds.
      The -57C/T variant was found on 2 of the 3 farms with endemic R. equi pneumonia,
      representing 2 different horse breeds. Significant allelic and genotypic
      associations with susceptibility to R. equi pneumonia were observed for the 
      57C/T variant in foals from these farms. Although the functional impact of this
      novel variant remains to be determined, this study represents an important step
      in our understanding of natural resistance to R. equi foal pneumonia and other
      intracellular bacterial diseases affecting equids.

PMID- 16955826
TI  - Preoperative administration of hydroxyethyl starch or hypertonic saline to horses
      with colic.
AB  - BACKGROUND: Hypertonic saline and hydroxyethyl starches have been proposed as
      alternatives to isotonic crystalloids for reversal of hypovolemia in horses with
      colic. However, no direct comparison of these fluids has been performed in a
      clinical setting. HYPOTHESIS: Preoperative administration of hypertonic saline or
      pentastarch would produce similar effects on intra operative hemodynamics in
      horses with colic. ANIMALS: Thirty horses requiring colic surgery were enrolled
      in this prospective, randomized, open-label clinical trial. Inclusion criteria
      were owner consent, and at least 2 of 3 clinicopathologic abnormalities: packed
      cell volume >45%, plasma total solid concentration >8.0 g/dL, and blood lactate
      concentration >2.5 mM. METHODS: Study horses were randomly assigned to receive 4
      mL/kg hypertonic saline or pentastarch before induction of anesthesia.
      Hemodynamic measurements were recorded every 30 minutes during anesthesia.
      Cardiac output (CO) was measured by the lithium dilution method. CO and stroke
      volume (SV) were indexed by body weight. Data were analysed using repeated
      measures analysis of variance (ANOVA). Post hoc comparisons were performed using
      the Bonferroni test. RESULTS: Cardiac index (CI) was higher in the pentastarch
      group compared with the hypertonic saline group from 30 to 150 minutes after
      induction (P = .04). SV index was higher in the pentastarch group at 30 (P =
      .025) and 60 minutes (P = .04). Mean arterial pressure of horses in both groups
      was lower at 90 minutes compared with 30 and 60 minutes. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Preoperative administration of pentastarch results in better CI than
      hypertonic saline, for 150 minutes after anesthetic induction. The effect of this
      improved global blood flow on regional perfusion or clinical outcome remains to
      be elucidated.

PMID- 16955827
TI  - Evaluation of the combined dexamethasone suppression/ thyrotropin-releasing
      hormone stimulation test for detection of pars intermedia pituitary adenomas in
      horses.
AB  - BACKGROUND: A combined dexamethasone (DEX) suppression/thyrotropin-releasing
      hormone (TRH) test (DEX/TRH test) has been developed to evaluate horses for
      presence of a pars intermedia pituitary adenoma (PIPA), but to the authors'
      knowledge, the accuracy of this test has not been previously determined.
      HYPOTHESIS: The sensitivity and specificity of the DEX/TRH test can be determined
      by comparing test results with histopathologic examination findings. ANIMALS: Age
      of 42 horses of various breeds ranged from 2 to 33 years. METHODS: Plasma
      cortisol concentration was measured before and 24 hours after IV administration
      of 40 microg of DEX/kg of body weight, and before and 30 minutes after IV
      administration of 1 mg of TRH that had been given 3 hours after the injection of
      DEX. Results of the DEX/TRH test were considered positive if either the plasma
      cortisol concentration exceeded 10 ng/mL 24 hours after DEX administration, or if
      the change in plasma cortisol concentration 30 minutes after injection of TRH was
      > or = 66% above the 3-hour baseline. Diagnosis of PIPA was determined by
      histologic examination of the pituitary gland. RESULTS: PIPA was detected in 17
      of 42 (40%) horses. The DEX/TRH test had sensitivity, specificity, positive
      predictive value, and negative (NPV) predictive value of 88, 76, 71, and 90%,
      respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: The combined DEX/TRH test was
      more sensitive than either of its component tests and had a high NPV, but was not
      as specific as the TRH component alone (92%). The DEX/TRH test should be used to
      screen older horses for PIPA.

PMID- 16955828
TI  - Persistence of serum antibodies to Sarcocystis neurona in horses moved from North
      America to India.
AB  - BACKGROUND: The study reported here was undertaken to assess the presence of
      antibodies to Sarcocystis neurona in the serum of horses of North American origin
      that had been relocated for 1 year or more to India (ie, outside of the known
      endemic areas for S. neurona). HYPOTHESIS: The presence or absence of such
      antibodies should provide information concerning the persistence of such
      antibodies, or support the presence of chronic infection, or both. ANIMALS: A
      total of 228 Thoroughbred horses were sampled in India, of which 86 were of North
      American origin that had been in India between 1 and 13 years, 124 were Indian
      born horses that had never been out of India, 8 were of Irish origin, 8 were of
      English origin, and 2 were originally from France. METHODS: Sera were tested
      using established western blot analysis. RESULTS: Of the Indian-born horses, 0.8%
      were test positive, and of the North American horses, 42% were test positive. All
      of the English and Irish horses were test negative, and the 2 French horses were
      test positive. CONCLUSIONS AND CLINICAL IMPORTANCE: These data indicate that
      antibodies against S. neurona can be detected for many years after horses have
      been removed from an endemic area and that this may be attributable to long half
      life of the antibodies or to chronic infection and ongoing antibody production,
      or both.

PMID- 16955829
TI  - Rattlesnake envenomation in 12 New World camelids.
AB  - BACKGROUND: Rattlesnake envenomation of New World camelids is a seasonal problem
      with often dramatic clinical signs. HYPOTHESIS: The purpose of this study was to
      identify the clinical signs, laboratory results, treatment methods, and outcome
      for rattlesnake envenomation in New World camelids. ANIMALS: Medical records from
      1988 to 2004 were searched for New World camelids presented for rattlesnake bite
      or clinical signs suspected to be related to recent envenomation. Twelve records
      were identified. METHODS: From these records a retrospective study was performed.
      RESULTS: Nine camelids presented for acute disease (2/9 arrived dead), whereas 3
      presented for subacute onset of disease. Swelling of the lips, head and neck,
      tachypnea, dyspnea, tachycardia, and lethargy were the most common presenting
      signs. Snake bites were most commonly located to the muzzle (10/12). Common
      complete blood count (CBC) and serum biochemical abnormalities were neutrophilia,
      lymphopenia, increased muscle enzyme activity, hypoalbuminemia, hyperglycemia,
      hypokalemia, and thrombocytopenia. Treatment included combinations of intravenous
      fluid therapy, antimicrobials, anti-inflammatory drugs, tetanus prophylaxis,
      tracheostomy, supplemental oxygen, antivenom, total parenteral nutrition, and
      nursing care. Five of the 10 animals with acute onset of clinical signs survived,
      and all animals with subacute presentation died. The mortality rate for New World
      camelids with severe local tissue reaction and systemic signs of envenomation was
      58%. CLINICAL IMPORTANCE: New World camelids that sustain rattlesnake
      envenomation and severe facial swelling precluding prehension and mastication
      have a guarded prognosis for survival. Aggressive treatment is recommended to
      optimize the chances of survival. Animals with less severe local tissue reaction
      and absence of systemic signs have a better prognosis.

PMID- 16955830
TI  - Floppy kid syndrome caused by D-lactic acidosis in goat kids.
AB  - BACKGROUND: Goat kids with floppy kid syndrome have metabolic acidosis, muscle
      weakness, and depression but no dehydration. HYPOTHESIS: D-Lactate is the major
      component of acidemia in goat kids with floppy kid syndrome. ANIMALS: Fifty-five
      goat kids with floppy kid syndrome (group F) and 35 clinically healthy goat kids
      (group C). METHODS: Clinical, biochemical, microbiologic, virologic,
      parasitologic, and pathologic examinations. RESULTS: The animals in group F had a
      blood pH of 7.13 +/- 0.11 and a base excess of -17.8 +/- 3.8 mM, which were both
      lower than the values in the control animals (pH, 7.32 +/- 0.31; base excess, 
      0.1 +/- 2.7 mM; P < .001). Floppy kids had a significantly larger anion gap than
      healthy kids (31.2 +/- 3.7 versus 21.5 +/- 8.5 mM; P < .001). The concentration
      of L-lactate was lower in floppy kids than in healthy kids (0.67 +/- 0.49 versus
      1.60 +/- 1.02 mM), but the concentration of D-lactate was higher in floppy kids
      (7.43 +/- 2.71 versus 0.26 +/- 0.24 mM; P < .001). Intravenous and oral
      administration of sodium bicarbonate in floppy kids resulted in a significant
      increase in blood pH and base excess and a decrease in the anion gap (P < .001).
      In addition, the concentration of L-lactate increased (P = .039). CONCLUSIONS AND
      CLINICAL IMPORTANCE: Metabolic acidosis in goat kids with floppy kid syndrome is
      caused by an increase in the plasma concentration of D-lactate.

PMID- 16955831
TI  - Angiotrophic T-cell lymphoma as a cause of regenerative anemia in a horse.

PMID- 16955832
TI  - Suspected complex regional pain syndrome in 2 horses.

PMID- 16955833
TI  - Hypoglycemia and tumor lysis syndrome associated with peritoneal mesothelioma in
      a horse.

PMID- 16955834
TI  - Alpha1-proteinase inhibitor deficiency and Bartonella infection in association
      with panniculitis, polyarthritis, and meningitis in a dog.

PMID- 16955835
TI  - Hypernatremia and hyperlipidemia in a dog with central nervous system
      lymphosarcoma.

PMID- 16955836
TI  - Meningoencephalomyelitis caused by Pasteurella multocida in a cat.

PMID- 16955837
TI  - Pulmonary thromboembolism in a heartworm-positive cat.

PMID- 16955838
TI  - Portosystemic shunt associated with severe episodic weakness.

PMID- 16955839
TI  - Passive transfer of naturally acquired specific immunity against West Nile Virus
      to foals in a semi-feral pony herd.
AB  - Horses naturally exposed to West Nile Virus (WNV) or vaccinated against WNV
      develop humoral immunity thought to be protective against development of clinical
      disease in exposed or infected animals. No reports evaluate the efficacy of
      passive transfer of naturally acquired specific WNV humoral immunity from dam to
      foal. The purpose of this study was to investigate passive transfer of naturally
      acquired immunity to WNV to foals born in a herd of semi-feral ponies, not
      vaccinated against WNV, in an endemic area, with many dams having seroconverted
      because of natural exposure. Microwell serum neutralization titers against WNV
      were determined in all mares and foals. Serum IgG concentration was determined in
      foals by serial radial immunodiffusion. Differences in IgG concentration between
      seropositive and seronegative foals were examined by means of the Mann-Whitney U
      test. Linear regression was used to evaluate the association between mare and
      foal titers. Seventeen mare-foal pairs were studied; 1 foal had inadequate IgG
      concentration. IgG concentration was not different between seronegative and
      seropositive foals (P = .24). Mare and foal titers were significantly correlated
      in foals with adequate passive transfer of immunity (Spearman's rho = .84; P <
      .001); >90% of the foal's titer was explained by the mare's titer (R2 = 0.91; P <
      .001). Passive transfer of specific immunity to WNV is present in pony foals with
      adequate passive transfer of immunity born to seroconverted mares.

PMID- 16955840
TI  - [Quality estimation and influence factors of the larger chemically acellular
      nerve allografts in vitro].
AB  - OBJECTIVE: To investigate the preparing procedures for the larger chemically
      acellular nerve allografts (CANA) and to establish an evaluation criteria and the
      preparation method. METHODS: The sciatic nerves of the dogs were exposed by a
      muscle-splitting incision and were isolated free of the underlying fascia. The 50
      mm-long segments of the nerve were made. The proximal and distal ends of the
      nerve segments were labelled and stabilized by pinning the ends to a thin plastic
      support, and then they were treated according to the following decellularization
      processes: The nerve segments were rinsed with the distilled water for 9 h,
      transferred in a 3% Triton-100 solution for 12 h, soaked in 7% sodium
      deoxycholate for 12 h, and washed in the distilled water for 6 h. All the
      decellularization steps were performed at room temperature. The nerve segments
      were divided into 5 subgroups. In Group I, Group II and Group III, the nerve
      segments were decellularized for 2, 3 and 4 times, respectively. In Group IV and
      Group V, the two ends of the nerve segments were ligated with a silk line and
      were decellularized for 2 and 3 times, respectively. Each nerve segment was
      subdivided into 5 portions from the proximal end to the distal end. The degrees
      of decellularization, activity of Laminin, degrees of demyelination, and
      integrity of the nerve fiber tube were observed under microscope and were
      assessed by a scoring system. RESULTS: In all the groups the activity of Laminin
      was present and the degrees of decellularization were complete. As for the
      demyelination of the nerve segments, the myelin sheath in Groups I, II and III
      was partially preserved, but it completely disappeared in Groups IV and V. The
      structure of the nerve fiber tube in Groups I and IV was almost normal. The total
      score for the degrees of decellularization, demyelination, and structural
      integrity was the lowest in Group IV but the quality was the best. CONCLUSION:
      The degrees of demyelination are not parallel to the times of decellularization
      processes. In the quality control of CANA, we should consider the following 4
      factors: activity of Laminin, degrees of decellularization, demyelination, and
      structural integrity. For the larger CANA, ligation of the two ends of the nerve
      segments during the decellularization procedure may be a better method of
      ensuring the quality of the decellularization.

PMID- 16955841
TI  - [The in vitro study of the human adipose tissue-derived stromal cells
      differentiating into the neuron-like cells].
AB  - OBJECTIVE: To investigate the possibility of the adipose tissue derived stromal
      cells (ADSCs) to differentiate into the neuron-like cells and to explore a new
      cell source for the transplantation related to the central nervous system.
      METHODS: Adipose was digested by collagenase, cultured in the fetal bovine serum
      containing a medium. Trypse was used to digest the cells and the cell passage was
      performed. The 3rd to the 9th passage ADSCs were used to make an induction.
      Isobutyl-methylxanthine, indomethacin, insulin, and dexamethasone were used to
      induce the ADSCs to differentiate into the neuronlike cells and adipocytes. Sudan
      black B and immunocytochemistry were used to identify the cells. RESULTS: A
      population of the ADSCs could be isolated from the adult human adipose tissue,
      they were processed to obtain a fibroblast-like population of the cells and could
      be maintained in vitro for an extended period with the stable population
      doubling, and they were expanded as the undifferentiated cells in culture for
      more than 20 passages, which indicated their proliferative capacity. They
      expressed vimentin and nestin, and characteristics of the neuron precursor stem
      cells at an early stage of differentiation. And the majority of the ADSCs also
      expressed the neuron-specific enolase and beta III-tubulin, characteristics of
      the neurons. Isobutyl-methylxanthine, indomethacin, insulin, and dexamethasone
      induced 40%-50% of ADSCs to differentiate into adipocytes and 0. 1%-0.2% of ADSCs
      into neuron-like cells. The neuron-like cells had a complicated morphology of the
      neurons, and they exhibited a neuron phenotype, expressed nestin, vimentin,
      neuron-specific enolase and beta III-tubulin, but some neuron-like cells also
      expressed the smooth muscle actin (SMA), and the characteristics of the smooth
      muscle cells; however, the neurons from the central nervous system were never
      reported to express this kind of protein. Therefore, the neuron-like cells from
      the ADSCs could be regarded as functional neurons. CONCLUSION: Our results
      support the hypothesis that the adult adipose tissue contains the stem cells
      capable of differentiating into the neuron-like cells, and they can overcome
      their mesenchymal commitment, which represents an alternative autologous stem
      cell source for transplantation related to the central nervous system.

PMID- 16955842
TI  - [Morphologic research on PDLLA/NGF-controlled release conduit promoting
      peripheral nerve regeneration].
AB  - OBJECTIVE: To establish an animal model for repairing the sciatic nerve defect
      with a biodegradable poly D,L-lactic acid/nerve growth factor (PDLLA/NGF) that
      can control the release conduit in rats and to observe an effect of the conduit
      on the sciatic nerve regeneration. METHODS: The PDLLA conduit and the PDLLA/NGF
      controlled release conduit (NGF 450 U per conduit) were made with the solvent
      volatilization method. Forty male SD rats were randomly and equally divided into
      4 groups. The middle segments (10 mm) of the sciatic nerves of the rats were
      excised and were then repaired with the sciatic nerve autograft (Group A), with
      the PDLLA conduit (Group B), with the PDLLA conduit and an injection of NGF (30
      U) into the conduit (Group C), and with the PDLLA/NGF controlled-release conduit
      (Group D), respectively, with the 10-mm nerve defect left behind. Three months
      after operation, the morphologic parameters of the nerve regeneration were
      observed and evaluated under light microscope and electron microscope, and the
      image analysis was also made. RESULTS: Three months after operation, porous
      adherence between the conduit and the surrounding tissues could be observed. The
      conduit presented a partial biodegradation but still remained intact in the
      outline and the proximal nerve regenerated through the conduit cavity. Based on
      the histological observation, the quantity, uniformity, and maturity of the nerve
      fiber regeneration in Groups A and D were better than those in Groups B and C.
      The image analysis indicated that there were no significant differences in the
      nerve fiber diameter, axon diameter or myelin thickness between Group A and Group
      D (P > 0.05). However, all the parameters in Groups A and D were better than
      those in Groups B and C (P < 0.05). CONCLUSION: The PDLLA/NGF-controlled release
      conduit can effectively promote the sciatic nerve regeneration of rats. Its
      morphological index is similar to that of the nerve autograft.

PMID- 16955843
TI  - [An effect of the peripheral nerve allograft with subcutaneous preservation at
      different times on the nerve regeneration].
AB  - OBJECTIVE: To study an effect of the peripheral nerve allograft with subcutaneous
      preservation at different times on the sciatic nerve regeneration in rats.
      METHODS: Fifty-five Wistar rats were used in this experiment, which were randomly
      divided into the following 5 groups: the experimental groups (Groups A, B, C, 10
      rats), the control group (Group D, 10 rats), and the donor group (Group E, 15
      rats). In the experimental groups, a 15-mm segment of the sciatic nerve harvested
      from the donors was separately inserted into the subcutaneous compartment on the
      left thigh after the 1-week (Group A), 2-week (Group B), and 3-week (Group C)
      preservation; the segment of the sciatic nerve in the subcutaneous compartment
      was removed and transplanted into a 10-mm defect of the right sciatic nerve,
      which was made immediately. In Group D, a 10-mm sciatic nerve defect was made and
      immediately repaired in situ on the right thigh. The function of the sciatic
      nerve was evaluated by the sciatic functional index (SFI) at 2, 4, 6, 8, 10 and
      12 weeks after operation. The histological and electrophysiological examinations
      were performed at 12 weeks after operation. RESULTS: After operation, SFI
      decreased gradually at 12 weeks after operation, SFI in Groups A and D was at the
      minimal level and had a significant difference compared with that in Groups B and
      C (P < 0.05). There was no significant difference between Group A and Group D. A
      large number of the myelinated nerve fibers and a small number of the
      unmyelinated nerve fibers were regenerated in Groups A and D. The number and the
      structure of the regenerated nerve were similar to the normal ones. The number
      and the size of the regenerated axon had a significant difference compared with
      those in Groups B and C (P < 0.05). There was no significant difference between
      Group A and Group D. The conduction velocity and the latent period of the motor
      nerve had significant differences between Groups A and D and Groups B and C (P <
      0.05), and there was no significant difference between Group A and Group D.
      CONCLUSION: The nerve allograft with a 1-week subcutaneous preservation can
      promote nerve regeneration better.

PMID- 16955844
TI  - [An effect of the omental wrapping on revascularization and nerve regeneration of
      the artificial nerve graft].
AB  - OBJECTIVE: To explore an effect of the artificial nerve graft wrapped in the
      pedicled greater omentum on the early revascularization and an effect of the
      increased blood supply to the artificial nerve graft on the nerve regeneration.
      METHODS: Seventy-five rabbits were randomized into 3 groups, in which there were
      2 experimental groups where the rabbits were made to abridge respectively with
      the artificial nerve grafts wrapped in the pedicled greater omentum (Group A) and
      with the artificial nerve grafts only (Group B), and the control group where the
      rabbits were abridged with the autologous nerve (Group C). On the 3rd, 7th and
      14th days after operation, the evans blue bound to albumin (EBA) was injected
      into the vessels in all the grafts to show their revascularization. Twelve weeks
      after operation the nerve regeneration was evaluated with the
      electrophysiological and histological observations on the serial sections, and
      was evaluated also with the transmission electron microscope. RESULTS: The
      artificial nerve grafts wrapped in the pedicled greater omentum in Group A and
      the autologous nerve grafts in Group C showed a beginning of revascularization on
      the 3rd day after operation, and the revascularization was increased on the 7th
      and 14th days. Compared with Groups A and C, the artificial nerve grafts in Group
      B showed a delayed revascularization on the 7th day after operation. At 12 weeks
      after operation, there were no significant differences in the motor never
      conduction velocity, density of the regenerated myelinated nerve fibers, myelin
      sheath thickness, and diameter between Group A and Group C (P > 0.05). However,
      both Group A and Group C were superior to Group B in the above variables, with
      significant differences (P < 0.05). CONCLUSION: Utilization of the pedicled
      greater omentum to wrap the artificial nerve grafts can promote an early
      revascularization of the artificial nerve graft and an early nerve regeneration
      of the artificial nerve graft because of an enhanced blood supply to the nerve
      graft.

PMID- 16955845
TI  - [An effect of the two-step freezing method on the Schwann cell biological
      activity in the peripheral nerve of the rat].
AB  - OBJECTIVE: To investigate an effect of different temperature cryopreservation of
      the two-step freezing method on the Schwann cell biological activity in the
      peripheral nerve of the rat. METHODS: Eighty female SD rats were randomly divided
      into 8 groups of 10 rats each. One was the control group and 7 were the
      experimental groups. Two 2-cm-long sciatic nerve segments were respectively taken
      from both legs of each rat. In the control group, the sciatic nerve segments did
      not undergo the treatment of cryopreservation; however, in the 7 experimental
      groups, the sciatic nerve segments respectively underwent the different
      temperature cryopreservation of the two-step freezing method at -20 degrees C, 
      30 degrees C, -40 degrees C, -50 degrees C, -60 degrees C, -70 degrees C and -80
      degrees C. The sciatic nerve segments were cryopreserved for 2 hours,and then
      placed into the liquid nigrtrogen at -196 degrees C. After 48 hours of storage,
      the nerve segments were thawed quickly in the 37 degrees C water bath box for 1
      minute. Then, the sciatic nerve segments each group were harvested. The cells of
      the sciatic nerve were incubated with Calcein-AM for 15 minutes. The average
      fluorescence intensity of the cells was measured by the flow cytometry. The nerve
      fibers were also incubated with Calcein-AM for 15 minutes. The fluorescence
      intensity of the cells was analyzed by the confocal fluorescence microscope. The
      Schwann cell biological activity intensity was measured. RESULTS: The
      fluorescence intensity in the -40 degrees C group was the strongest and the
      Schwann cell biological activity in this group was the best among all the groups
      (P < 0.01). The fluorescence intensity in the 8 groups measured by the flow
      cytometry was as follows: 242.5220 +/- 9.5684 in the control group, 168.6770 +/-
      10.2070 in the -20 degrees C group, 214.9920 +/- 8.3291 in the -30 degrees C
      group, 235.5260 +/- 9.2805 in the -40 degrees C group, 222.4340 +/- 8.5155 in the
      -50 degrees C group, 217.4090 +/- 9.5157 in the -60 degrees C group, 132.3760 +/-
      13.4597 in the -70 degrees C group, and 108.1320 +/- 16.0331 in the -80 degrees C
      group. The fluorescence intensity detected by the confocal fluorescence
      microscope was as follows: 143.7000 +/- 5.5678 in the control group, 119.7000 +/-
      5.161 5 in the -20 degrees C group, 121.3000 +/- 4.3474 in the -30 degrees C
      group, 139.7000 +/- 5.0122 in the -40 degrees C group, 121.0000 +/- 4.5461 in the
      -50 degrees C group, 118.4000 +/- 4.9261 in the -60 degrees C group, 81.2000 +/-
      5.1164 in the -70 degrees C group, and 79.0000 +/- 5.7164 in the -80 degrees C
      group. CONCLUSION: The Schwann cell biological activity treated by the two-step
      freezing method can be preserved and the activity is cryopreserved best at -40
      degrees C.

PMID- 16955846
TI  - [Inhibitor of nitric oxide synthase on the denervated muscle atrophy].
AB  - OBJECTIVE: To study the effect of the competitive inhibitor of nitric oxide
      synthase N(G)-nitro-L-arginine methyl ester (L-NAME) on the denervated muscle
      atrophy. METHODS: A model of the denervated gastrocnemius at the right lower limb
      was established in 36 SD adult rats. The rats were randomly divided into two
      groups: the L-NAME group (Group A) and the control group (Group B). L-NAME 10
      mg/kg daily was injected into the denervated gastrocnemius in Group A, and normal
      saline was injected into the denervated gastrocnemius in Group B. At 2, 4 and 8
      weeks after operation, the rate of the muscle wet weight preservation, the cross
      section area of the myocyte, the protein amount, and the percentage of the
      apoptotic muscle cells were measured respectively and the ultramicrostructure of
      the myocyte was observed. RESULTS: At 2 and 4 weeks after operation, the rate of
      the muscle wet weight preservation, the cross section area of the myocyte, and
      the protein amount were significantly greater in Group A than in Group B;
      however, the percentage of the apoptotic muscle cells was significantly smaller
      in Group A than in Group B. The observation of the ultramicrostructure of the
      myocyte showed that an injection of L-NAME could protect the ultramicrostructure
      of the myocyte. At 8 weeks after operation, there was no significant difference
      between the two groups in the above-mentioned parameters. CONCLUSION: The nitric
      oxide synthase inhibition can delay the denervated muscle atrophy.

PMID- 16955847
TI  - [Therapeutic effect evaluation of ulnar neurolysis and nerve anterior
      transposition with an immediate range of motion in the aged].
AB  - OBJECTIVE: To investigate the clinical therapeutic effect of the ulnar neurolysis
      and nerve anterior transposition with an immediate range of motion for the
      cubital tunnel syndrome in the aged. METHODS: Forty-three patients (24 males and
      19 females, aged 60-81 years, averaged 67) admitted for the cubital tunnel
      syndrome from January 1999 to December 2004 were randomly divided into 2 groups:
      Group A (n=20) and Group B (n=23), with an illness course of 2-10 months. All the
      patients underwent the ulnar neurolysis and the nerve anterior transposition.
      After operation the patients' elbows in group A were immobilized with the plaster
      slab for an external fixation for 3 weeks; the patients' elbows in group B did
      not use the external fixation, but began an immediate range of motion on the 2nd
      day after operation. The Bishop scoring system was used to evaluate the patients'
      functional recovery in the 2 groups. RESULTS: The follow-up for 1-5 years showed
      that the ulnar nerve function of all the patients were improved but no
      significant differences were found between the 2 groups (P > 0.05). The patients
      in Group A returned to daily activities or work at 45.2 +/- 5.1 days, but the
      patients in Group B required 15.5 +/- 3.8 days, with a significant difference
      between the 2 groups (P < 0.05). According to Bishop scoring system, the results
      were excellent in 14 cases, good in 4 cases, fair in 1 case and poor in 1 case in
      Group A, and 16, 4, 2 and 1 respectively in Group B. There was no significant
      difference between the two groups (P > 0.05). CONCLUSION: The ulnar neurolysis
      and nerve anterior transposition with an immediate range of motion for the
      cubital tunnel syndrome can promote the ulnar function recovery of the old-aged
      patients. They can return to their daily activities or work at a more rapid speed
      when their elbows are mobilized immediately after operation.

PMID- 16955848
TI  - [Experimental study on the artificial bladder reflex arc established in therapy
      of flaccid bladder after spinal cored injury].
AB  - OBJECTIVE: To establish the artificial bladder reflex arc by the normal body
      reflex pathway above the horizon of spinal cord injury to reinnervate the flaccid
      bladder and restore bladder micturition function. METHODS: An intradural
      microanastomosis was performed on the L6 ventral root to the S2 ventral root.
      After axonal regeneration,the "patellar ligament-spinal cord center-bladder"
      reflex pathway was reestablished. A long-term function of the reflex arc was
      observed in the nerve electrophysiological experiment, detrusor electromyography
      experiment, and urodynamic testing 8 months after anastomosis. RESULTS: Trains of
      the stimuli (200 microV, 5 ms) in the left L6 dorsal root and the nerve at the
      anastomosized site resulted in motor evoked potential from the distal to the
      anastomosized site before and after the spinal cord was destroyed horizontally
      between S1 and S4 segment levels in 2 Beagle dogs. The figure and amplitude of
      the evoked potential were similar to those of the control and general stability
      which showed a noninterventional wave. The urodynamic test revealed a rapid
      increase of the bladder pressure and a minor increase in the abdominal pressure.
      This showed that the bladder detrusor mainly resulted in the pressure increase.
      The bladder pressure increased to 60% of the normal on average compared with the
      controls when resulted in the left L6 dorsal root and the nerve anastomosized
      site were stimulated. CONCLUSION: The long-term observation by the nerve
      electrophysiological experiment, detrusor electromyography experiment, and
      urodynamic test indicate that the new artificial reflex arc can be established
      successfully. The somatic motor axons can regenerate into the parasympathetic
      endoneurial tubes of the autonomic nerve.

PMID- 16955849
TI  - [Experimental research of allogeneic bone sheet in preventing epidural adhesion].
AB  - OBJECTIVE: To study the effect of the allogeneic bone sheet that has been treated
      by the freeze-drying and radiation sterilization in preventing the epidural
      adhesion after laminectomy in sheep. METHODS: Laminectomy was performed on L(3,4)
      and L(1,5) of 12 adult male sheep. After operation, one site of L(3,4) or was
      covered by the allogeneic bone sheet in "H" shape after the freeze-drying and
      radiation sterilization treatment; and the other site was used as a control. The
      sheep were killed and the specimens were retrieved at 4, 8, 12, 16, 20 and 24
      weeks after operation to observe the scar formation process. X-ray and CT scan
      were performed in the segments of L(3,4) and L(4,5) at 4 and 24 weeks. RESULTS:
      Four weeks after operation, the position and the shape of the allogeneic bone
      sheet were good in condition, and no lumbar spinal stenosis or compression of the
      dura was found in the experimental sections. Twenty-four weeks after operation
      the examination on the experimental sections revealed that the vertebral canal
      reconstruction was completed, the allograft was absorbed almost completely, and
      inoculation with the lamina of the vertebra and the shape of the lumbar spine
      were good, with no fibroid tissues found in the epidural area. Compared with the
      control segment, the dura adhesion degree in the laminoplasty segment was
      significantly decreased (P < 0.01), and the dura sac remained in a good shape.
      There was no obvious compression on the dura. CONCLUSION: The allogeneic bone
      sheet after the treatment of freeze-drying and radiation sterilization can
      effectively reduce the scar formation after laminectomy and prevent postoperative
      recurrence of the spinal stenosis.

PMID- 16955850
TI  - [Adenovirus-mediated human bone morphogenetic protein 2 gene transferred to
      rabbit intervertebral disc cells in vitro].
AB  - OBJECTIVE: To study the adenovirus-mediated human bone morphogenetic protein-2
      gene (Ad-hBMP-2)transferred to the intervertebral disc cells of the New Zealand
      rabbit in vitro. METHODS: The cells of New Zealand white rabbits were isolated
      from their lumbar discs. The cells were grown in the monolayer and treated with
      an adenovirus encoding the LacZ gene (Ad-LacZ) and Ad-hBMP-2 (50, 100, 150 MOI,
      multiplicity of infection) in the Dulbecco's Modified Eagle Medium and the Ham's
      F-12 Medium in vitro. Three days after the Ad-hBMP-2 treatment, the expression of
      hBMP-2 in the cells that had been infected by different doses of MCI was
      determined by immunofluorescence and the Western blot analysis, and the
      expression was determined in the cells with the Ad-LacZ treatment in a dose of
      150 MDI. Six days after the Ad-hBMP-2 treatment, mRNA was extracted fur the
      reverse transcription polymerase chain reaction (RT-PCR) and the difference was
      detected between the control group and the culture group that was treated with Ad
      hBMP-2 in doses of 50, 100 and 150 MCI so that the expressions of aggrecan and
      collagen II mRNA could be observed. RESULTS: The expression of hBMP-2 in the
      cells was gradually increased after the transfection in an increasing dose, which
      was observed by immunofluorescence and the Western blot analysis. At 6 days the
      aggrecan and collagen type II mRNA expressions were up-regulated by Ad-hBMP-2
      after the transfection at an increasing viral concentration in the dose-dependent
      manner. CONCLUSION: The results show that Ad-hBMP-2 can transfect the rabbit
      intervertebral disc cells in vitro with a high efficiency rate and the expression
      of hBMP-2 after the infection is dose-dependent in the manner. Ad-hBMP-2 after
      transfection can up-regulate the expression of aggrecan and collagen IL mRNA at
      an increasing viral concentration.

PMID- 16955851
TI  - [Fusion of reconstructed titanic plate, vertebral pedical screws and autogenous
      granulated cancellous bone graft in posterior occipitocervical region].
AB  - OBJECTIVE: To explore the technique of fusing the reconstructed titanic plate,
      the C2 pedical screws, and the autogenous granulated cancellous bone graft in the
      occipitocervical region. METHODS: From April 2002 to January 2005, 19 patients
      aged 31-67 years with occipitocervical instability underwent the occipitocervical
      fusion using the reconstructed plate, C2 pedical screws, and autogenous
      granulated cancellous bone graft. Of the patients, 8 had complex occipitocervical
      deformity, 8 had old atlantoaxial fracture and dislocation, 2 had rheumatoid
      arthritis and anterior dislocation of the atlantoaxial joint, and 1 had cancer of
      the deltoid process of the axis. RESULTS: No complication occurred during and
      after operation. The follow-up for an average of 16 months in 19 patients showed
      that all the patients achieved solid bony fusion in the occipitocervical region.
      There was no broken plate, broken screw, looseness of the internal fixation or
      neurovascular injury. CONCLUSION: The fixation of the C2 pedical screws with the
      reconstructed titanic plate is reliable, the insertion is easy, and the
      autogenous granulated cancellous bone graft has a high fusion rate, thus
      resulting in a satisfactory effect in the occipitocervical fusion.

PMID- 16955852
TI  - [Comparison study between two types of vaginoplasty].
AB  - OBJECTIVE: To investigate the clinical therapeutic effects of two types of
      vaginoplasty. METHODS: From January 1996 to March 2005, 63 patients with the
      congenital absence of the vagina were treated by two types of vaginoplasty. Of
      the 63 patients, 37 underwent vaginoplasty using the amnion and 26 underwent an
      improved laparoscopic Vecchietti operation. The durations of the operation and
      hospitalization, as well as the blood loss were compared between the two types of
      vaginoplasty. The vaginal moulds were improved during the operations. RESULTS:
      According to the follow-up for 2 months to 4 years in the 35 patients. Compared
      with vaginoplasty using the amnion, vaginoplasty by an improved laparoscopic
      Vecchietti operation had advantages of significantly shorter surgical duration,
      shorter hospitalization, and less blood loss (P < 0.05). After the operations,
      the artificial vagina of all the 63 patients could hold a speculum and the mucosa
      appeared so soft and smooth with normal lubrication. The married patients were
      satisfied with the intercourse. However, after vaginoplasty using the amnion, an
      infection of the amnion occurred in 3 patients, scar contracture in 2 patients,
      one of whom underwent scar incision 13 months after operation with a success; but
      the other refuse to accept another operation. But the improved laparoscopic
      Vecchietti operation achieved a success in the patients without any infection or
      scar contracture, according to the 2 month-2.5 years follow-up. CONCLUSION: The
      improved laparoscopic Vecchietti operation is a preferred procedure of
      constructing a vagina for the patients suffering from the congenital absence of
      the vagina.

PMID- 16955853
TI  - [Repair of defects in chest wall with thoracico-abdominal skin flap and muscle
      flap of musculus rectus abdominis].
AB  - OBJECTIVE: To evaluate the application value of repairing the defects of the
      chest wall with the thoracico-abdominal skin flap and the muscle flap of the
      musculus rectus abdominis. METHODS: From January 2002 to June 2005, five patients
      with defects in the chest wall underwent the prosthesis with the thoracico
      abdominal skin flap and the muscle flap of the musculus rectus abdominis under
      general anesthesia. Focal cleaning was performed first; then, the skin flap was
      designed and taken (15 cm x 10 cm); and finally, the defects of the chest wall
      were repaired with the muscle flap of the musculus rectus abdominis. RESULTS: Of
      the 5 patients, 4 had the flap healing by the first intention, and 1 had the
      delayed healing, with no complication. The skin flap had a good appearance,
      without edema or pigmentation. The X-ray examination showed that the shadow of
      the sternal sequestrum disappeared. There was no recurrence or complication
      during the follow-up for 1-3 years (average, 18 mon). CONCLUSION: The repairing
      of the defects in the chest wall with the thoracico-abdominal skin flap and the
      muscle flap of the musculus rectus abdominis is a simple and effective surgical
      treatment for defects of the chest wall around the sternum, and this kind of
      treatment is worth applying extensively in clinical practice.

PMID- 16955854
TI  - [Diagnosis and treatment of gluteal muscle contracture associated with unequal
      leg length caused by pelvis obliquity].
AB  - OBJECTIVE: To investigate the pathogenesis, diagnosis, and treatment of the
      gluteal muscle contracture associated with an unequal leg length caused by the
      pelvis obliquity (GMC-PO). METHODS: The retrospective analysis was made on the
      clinical features and the follow-up results in 132 patients who had been admitted
      from January 1990 to December 2004 for GMC-PO. Among them, 73 were male and 59
      were female with a range in age from 5 to 26 years (average, 11 yr). All the
      patients were characterized by unsymmetrical contracture of the gluteal muscles,
      including unilateral and bilateral contracture. Of the patients, 89 had a clear
      limping and 78 had a clearly-unequal leg length. The X-ray examination revealed
      pelvis obliquity in 97 cases and an increased angle of the femur neck in 11
      cases. The arc longitudinal incision was made into the posterolateral area nearby
      the greater trochanter and then lysis of the gluteal muscles was performed,
      combined with the skin traction of both legs and exercise training. RESULTS: Of
      the 132 patients with unequal gluteal muscle contracture before operation, 13 had
      a relative length difference of 0.5-1.5 cm between the 2 legs, 1 had a difference
      of 3.0 cm, and the remaining 118 patients had an equal leg length. Excellent and
      good results were achieved in 118 and 13 patients, respectively after the
      surgical release of the gluteal muscle contracture by the arc longitudinal
      incision into the posterolateral area nearby the greater trochanter, combined
      with postoperative skin traction and functional exercises. Only 1 patient had a
      poor result. The follow-up for 3 months to 14 years showed that the cure rate was
      as high as 99.2%. CONCLUSION: The gluteal muscle contracture associated with an
      unequal leg length caused by the pelvis obliquity is a result of the unequal
      gluteal muscle contracture between the 2 hips and it can be cured with a
      comprehensive therapeutic method including the surgical release of the gluteal
      muscle contracture by the are longitudinal incision into the posterolateral area
      nearby the greater trochanter, and postoperative skin traction as well as the
      functional exercise.

PMID- 16955855
TI  - [Treatment of complex acetabular fractures by a modified extended iliofemoral
      approach].
AB  - OBJECTIVE: To evaluate the effect of the modified extended iliofemoral approach
      on treating complex acetabular fractures. METHODS: Thirty-six cases of complex
      acetabular fractures were treated by the open reposition and internal fixation by
      a modified extended iliofemoral approach. RESULTS: Thirty-six cases were followed
      up for 7-46 months, with an average of 23.8 months. According to the Matta
      standard, anatomical reposition was performed in 24 cases, perfect reposition in
      8 cases, and unsatisfactory reposition in 4 cases. By the modified d'Aubigne
      postel score, among the 36 cases, 22 had an excellent result, 9 had a good
      result, and 5 had a poor result. CONCLUSION: The modified extended iliofemoral
      approach facilitates the operative exposure of the anterior and posterior walls
      and both columns of the acetabulum in the surgically-treated acetabular fractures
      by the open reposition and internal fixation. Because of the reconstruction, the
      functions of the abductor muscle mass managed by the lag-screw-fixed osteotomies
      of the iliac crest, and greater trochanter, the patients can achieve a rapid
      rehabilitation of the joint.

PMID- 16955856
TI  - [Redifferentiation of the dedifferentiated human articular chondrocytes by the
      bioreactor culturing].
AB  - OBJECTIVE: To examine the biological characteristic changes in the
      dedifferentiated human articular chondrocytes by the bioreactor culturing in
      vitro. METHODS: The cartilage tissue was obtained from the joints of the adult
      human. The chondrocytes were isolated from the cartilage tissue with the type II
      collagenase digestion (0.2%, 37 degrees C, 3 h)and were cultured in DMEM-F12
      supplemented with 20% fetal bovine serum (FBS) with 1 ng/ml of TGF-beta1, and 5
      ng/ml of FGF-2. After about 20 passages by the monolayer culture, the cells were
      then transferred to the bioreactor culturing of the rotational cell culture
      system (RCCS) for a 3-week sequence culture. The cell counting was performed with
      the platelet counter, and the doubling time for each passage of the cells was
      determined. The frozen section was stained with HE. The differentiated phenotype
      was evaluated by histochemistry or immunohistochemistry. RESULTS: When the
      monolayer culture was performed without any growth factors, the chondrocytes were
      rapidly proliferated within 3 passages (average doubling time, 59 h), but at the
      same time, differentiation was also progressing rapidly. After the 4th passage,
      most of the cells were differentiated and the proliferation was decreased. With
      the growth factors (TGF-beta1/FGF-2), the speed of the expansion was accelerated
      (average doubling time, 47 h), but the speed of the dedifferentiation was slowed
      down. After 20 passages were performed with the monolayer culture, the
      dedifferentiated chondrocytes could be redifferentiated when they were cultured
      for 3 weeks with RCCS. Then, the Safranine-O staining was strongly positive for
      the cells, positive for aggrecan and collagen II, but negative for collagen I,
      with a well-regained phenotype. CONCLUSION: The bioreactor culturing of the
      dedifferentiated human articular chondrocytes can regain the differentiated
      phenotype and it is a useful method of obtaining the human articular chondrocytes
      in large amounts and in a differentiated phenotype in vitro.

PMID- 16955857
TI  - [A morphological study of chondrogenesis by adipose-derived adult stem cells
      induced by recombinant human bone morphogenetic protein 2].
AB  - OBJECTIVE: To investigate the possibility of differentiation of the isolated and
      cultured adipose derived adult stem cells into chondrocytes, which is induced by
      the recombinant human bone morphogenetic protein 2 (rhBMP 2). METHODS: The rabbit
      adipose tissue was minced and digested by collagenase Type I. The adipose derived
      adult stem cells were obtained and then they were cultured in the micropellet
      condition respectively in the rhBMP-2 group, the rhTGF-beta1 group, the
      combination group, and the control group for 14 days. The differentiation of the
      adipose-derived stem cells into chondrocytes was identified by the histological
      methods including HE, Alcian blue, Von kossa, and immunohistochemical stainings.
      RESULTS: After the continuous induction by rhBMP-2 and continuous culture for 14
      days, the HE staining revealed a formation of the cartilage lacuna; Alcian blue
      indicated that proteoglycan existed in the extracellular matrix; the
      immunohistochemical staining indicated that collagen II was in the cellular
      matrix; and Von kossa indicated that the adipose-derived stem cells could not
      differentiate into the osteoblasts by an induction of rhBMP-2. CONCLUSION: In the
      micropellet condition, the adipose-derived adult stem cells can differentiate
      into the chondrocytes, which is initially induced by rhBMP-2. This
      differentiation can provide a foundation for the repair of the cartilage injury.

PMID- 16955858
TI  - [Development in transplantation of the skeletal muscle myoblast].
AB  - OBJECTIVE: To review the research progress in transplantation of the skeletal
      muscle myoblast. METHODS: The recently-published articles concerned with the
      myoblast transplantation were reviewed, including myoblast culture, modified
      transplant methods, preparation of the recipient, scaffold choice, and an
      influence of the recipient's immunity on the transplantation. How to improve the
      efficiency of the myoblast transplantation was also discussed. RESULTS: The
      techniques of the myoblast transplantation were improved and transplantation
      efficiency was increased. CONCLUSION: The transplantation of the skeletal muscle
      myoblast has a great potential value in clinical practice and a promising future
      in its clinical application.

PMID- 16955859
TI  - [Relationship between the central nervous system injury and the heterotopic
      ossification].
AB  - OBJECTIVE: To review the progress of the research on the relationship between the
      central nervous system injury and the heterotopic ossification. METHODS: The
      recent articles on the central nervous system injury and the heterotopic
      ossification were extensively reviewed, and the related clinical signs, symptoms,
      pathogenesis diagnosis, risk factors, prophylaxis, and treatment of the
      neurogenic heterotopic ossification were investigated. RESULTS: The possible
      mechanism for the neurogenic heterotopic ossification might involve the roles of
      the bone morphogenetic protein and the basic fibroblast growth factor, which were
      suggested as mediators in differentiation of the progenitor cells. Sonographic,
      serum creatine phosphokinase, and C-reactive protein were recommended as the
      useful screening tools for heterotopic ossification. Colchicine and rofecoxib
      could be used for the prophylaxis or treatment of heterotopic ossification.
      CONCLUSION: The research on the neurogenic heterotopic ossification has achieved
      a great development but further studies in this field are still required.

PMID- 16955860
TI  - Implementing patient safety practices in small ambulatory care settings.
AB  - BACKGROUND: Improving patient safety in the outpatient setting poses unique
      challenges for patient safety leaders in clinics and hospitals. Even though
      ambulatory care may be less technologically complex than inpatient care, it is
      often more complex logistically. METHODS AND MATERIALS: From October 2002 to May
      2003, Gundersen Lutheran Medical Center developed a tool kit of best practices
      and conducted a collaborative to institute these best practices within a regional
      health care network. All clinics evaluated patient safety standards and enhanced
      medication-related practices. RESULTS: Improvements were demonstrated in
      medication list accuracy. A number of policies were instituted, and medical and
      nursing staffs were educated in patient safety issues. Improvements were
      sustained after one year. DISCUSSION: The collaborative model of improvement
      efforts was an effective model for improving patient safety in small group
      practices. Structural and process changes often do not require major changes in
      workflow or large technology installations. Many of the projects allowed for, or
      required, local assessment and management. However, within a large system of
      clinics, some of the improvements in this study--verbal order policy, methodology
      and/or technology for assessment of medication and allergy list accuracy,
      warfarin care--required systemwide efforts. The degree of difficulty of achieving
      improvements was surprisingly low and barriers were minimal.

PMID- 16955861
TI  - Combining evidence and diffusion of innovation theory to enhance influenza
      immunization.
AB  - BACKGROUND: Children and adolescents with chronic conditions such as asthma,
      diabetes, and HIV are at high risk of influenza-related morbidity, and there are
      recommendations to immunize these populations annually. At Cincinnati Children's
      Hospital Medical Center, the influenza immunization rate increased to 90.4% (5%
      declined) among 200 patients with cystic fibrosis (CF). Diffusion of innovation
      theory was used to guide the design and implementation of spread to other
      clinics. METHOD: The main intervention strategies were: (1) engagement of
      interested, nurse-led teams, (2) A collaborative learning session, (3) A tool kit
      including literature, sample goals, reminder postcards, communication strategies,
      and team member roles and processes, (4) open-access scheduling and standing
      orders (5) A simple Web-based registry, (6) facilitated vaccine ordering, (7)
      recall phone calls, and (8) weekly results posting. RESULTS: Clinic-specific
      immunization rates ranged from 32.7% to 92.8%, with the highest rate reported in
      the CF clinic. All teams used multiple strategies; with six of the seven using
      four or more. Overall, 60.0% (762/1,269) of the population was immunized.
      Barriers included vaccine shortages, lack of time for reminder calls, and lack of
      physician support in one clinic. DISCUSSION: A combination of interventions,
      guided by evidence and diffusion of innovation theory, led to immunization rates
      higher than those reported in the literature.

PMID- 16955862
TI  - A leadership framework for culture change in health care.
AB  - BACKGROUND: In 2005, Ascension Health's strategic direction sharpened the focus
      of its 2002 Call to Action to provide "Healthcare That Works, Healthcare That Is
      Safe, and Healthcare That Leaves No One Behind, for Life," Ascension Health has
      used a framework, the Five Cs of Culture Change, to address the call to action-
      comprehension (understanding the problem), compassion (spirituality and
      commitment), collaboration (teaming between subcultures and providers),
      coordination (system processes, infrastructure, and ideation), and convergence
      (leadership of local culture with spread and dissemination of new norms in a
      rapid way). THE FIVE CS OF CULTURE CHANGE AND CULTURE SURVEYS: Climate (or
      culture) of safety results are provided from a baseline systemwide survey of
      front-line caregivers' assessments of teamwork and patient safety. The findings
      are aggregated at the hospital level, clinical area level, and caregiver role
      level, and fed back to executives, managers, and front-line caregivers. The final
      major element of culture change, and arguably the most important, involves the
      leadership and fortitude necessary to stimulate convergence of the culture on a
      new way of doing things. CONCLUSION: Ascension Health will continue to use a
      systemwide culture survey for front-line assessments' of safety and teamwork
      across all clinical areas and to discover best practices and track progress in
      improving performance.

PMID- 16955863
TI  - Paying physicians for quality: evidence and themes from the field.
AB  - BACKGROUND: Health plans, self-insured employers, health plans, and provider
      organizations are currently introducing financial incentives that reward
      physicians for delivering high-quality medical care. Yet a review of existing
      research reveals virtually no empirical studies of the effect of direct, internal
      quality incentives on physician performance. Key-informant interviews with
      leaders of provider organizations should shed new light on evolving quality
      incentives within organizations. METHODS: Structured key-informant interviews
      with administrators and medical directors in 22 medical groups and 9 hospitals
      affiliated with 10 large, integrated health systems were conducted from July 2003
      through January 2004. FINDINGS: Views on the role of financial incentives varied
      widely and were related to a number of other factors, including institutional
      culture, community context, organizational strategy and structure, organizational
      stability, quality measurement, nature and size of incentives, and the
      sustainability of interventions. DISCUSSION: These findings have implications for
      the acceptability and structure of financial incentives for quality directed to
      health care provider organizations. A set of considerations for the design and
      implementation of quality incentives relate to the incentives' scope,
      controllability, transparency, size, and orientation (individual or team), as
      well as the relationship between the extrinsic financial incentives and
      professionals' intrinsic motivation.

PMID- 16955864
TI  - Family members as proxies for satisfaction with nursing home care.
AB  - BACKGROUND: Many benefits to collecting and reporting satisfaction information
      from nursing home residents, including promoting quality initiatives, consumer
      choice, and improved care, have been described. Yet barriers to collecting
      resident satisfaction information exist, the most significant of which is the
      often low cognitive status of residents. An alternative source of information can
      come from family members serving as proxies for the residents. A study was
      conducted to explore the agreement and association of nursing home residents'
      responses with family member proxy responses. METHODS: Satisfaction data from 286
      paired residents and family members in 42 facilities were collected in 1999. The
      satisfaction questionnaire consisted of 16 items evaluating the art of care,
      technical quality, efficacy, amenities of the care environment, and global
      satisfaction. Bias indexes, intraclass correlation coefficients, and Pearson's
      product-moment correlation coefficients were used to compare resident and proxy
      responses. RESULTS: In general, proxy satisfaction ratings were higher than the
      same ratings given by residents. Proxy ratings varied less from residents'
      ratings for the amenities items, which were considered the most concrete items.
      Proxy ratings were much higher for the art of care and efficacy domain items--the
      least concrete questions. DISCUSSION: Proxy ratings do not necessarily substitute
      for resident ratings and are dependent on the nature of the question asked.
      Examining resident-proxy responses at different points in time may be useful.

PMID- 16955865
TI  - Using an MET service to manage hemorrhage post-percutaneous liver biopsy.
AB  - The hospital's medical emergency team expedited involvement of all required
      services when it was called in twice for episodes of bleeding.

PMID- 16955866
TI  - Helping hippocrates: a cross-functional approach to patient identification.
AB  - BACKGROUND: The Joint Commission on Accreditation of Healthcare Organizations
      National Patient Safety Goal 1, which requires the use of at least two patient
      identifiers, is the foundation for other patient safety goals. St. Francis
      Hospital involved staff and patients in the "Helping Hippocrates" Project, which
      used a "game" with staff and patients to ensure the accuracy of information on
      patients' identification (ID) bands. THE PROJECT: Members of all hospital
      departments assigned to a specific day were to compare the ID band with the
      patient census report and identify patients who had no ID band on their wrist and
      patients who had a band with inaccuracies. They were to also ask patients if the
      staff had checked the ID band before treatments or procedures. Also, the nurse
      manager was to select a patient to add to his or her own ID band a special band
      bearing the name Hippocrates. The department conducting the survey had to find
      Hippocrates. FINDINGS: Internal data showed that patient identification errors
      declined from 8.2% to a sustained zero. Patient satisfaction data showed that
      since the inception of Helping Hippocrates, patients' perceptions of staffs
      compliance with ID verification showed steady improvement. CONCLUSION: Helping
      Hippocrates demonstrates the value of using an innovative problem-solving
      strategy that engages the entire organization.

PMID- 16955867
TI  - Medication errors involving neuromuscular blocking agents.
AB  - Many of the errors involving these agents lie in dispensing or administration,
      which argues for the need to enhance practitioners' knowledge of and adherence to
      proper handling procedures and proper dosing.

PMID- 16955868
TI  - Tracking POPs across the planet.

PMID- 16955869
TI  - Efforts to stop groundwater pollution disappoint.

PMID- 16955870
TI  - Coal utilities gamble on carbon regulation.

PMID- 16955871
TI  - Canada eyes limits on nonstick chemicals.

PMID- 16955872
TI  - Keeping up with the Johnsons.

PMID- 16955873
TI  - Climate change and air quality--measures with co-benefits in China.

PMID- 16955874
TI  - Evaluating the quality of structured environmental management decisions.
AB  - Structured decision making (SDM) approaches have been advocated as a means of
      improving the quality of environmental and related risk management decisions
      based largely on the self-reported behavior of decision makers. The goal of the
      research presented here was to test this basis for decision quality by comparing
      the self-reported assessments of individual decision makers with their actual
      choice behavior across a set of three related environmental contexts. It was
      hypothesized that a modified structured decision approach would lead participants
      to make better informed decisions which accurately reflected their objectives,
      not based solely on self-reports, but also on internally consistent decision
      making behavior. Results from this study only partially support this hypothesis.
      While individuals' self-reports suggest that the structured approach outperformed
      results from an unstructured control condition, there was a lack of agreement
      between these self-reported evaluations and actual choice behavior. Beyond the
      obvious policy implications of decisions that are inconsistent with stated
      objectives, these findings point to the need for improved metrics when evaluating
      the quality of environmental decision processes.

PMID- 16955875
TI  - Considering user attitude in early Development of environmentally friendly
      technology: a case study of NoMix toilets.
AB  - Urine source separation (NoMix technology) has been proposed as a sustainable
      alternative to centralized wastewater treatment systems. Radical changes
      necessitate an early inclusion of sociological expertise, thus offering a real
      chance fortransdisciplinary collaboration. The practical aim of our survey is to
      find out how users accept and use existing NoMixtoilets and how this could be
      encouraged. We collected 1249 questionnaires from 2002 to 2004 in one Swiss
      school and one Swiss research institute. The technological immaturity of NoMix
      toilets was noted by many. Nevertheless, acceptance was high: 72% liked the idea
      and 86% would move into apartments with NoMix toilets. Moreover, most users found
      that NoMix toilets equal conventional toilets with respect to design (78%),
      hygiene (84%), and smell (78%). Like many other innovations, the NoMix technology
      only functions properly if it is used adequately, which we demonstrate for water
      saving and sitting to urinate. Many users adopted this behavior, e.g., 72% sat.
      Because perception and use of NoMix toilets is subjective, it can be influenced
      with certain measures such as good information and cleaning, or discussions with
      peers. We discuss the importance of social psychology for understanding the
      factors that influence the acceptance of environmentally friendly innovations.

PMID- 16955876
TI  - Reactivity-based VOC control for solvent products: more efficient ozone reduction
      strategies.
AB  - It has been almost 40 years since scientists and regulators began to publicly
      recognize that volatile organic compounds (VOCs) differ in their potential to
      form ozone. Since 1977, our understanding of the mechanisms by which VOCs
      contribute to ozone formation has grown substantially. An assessment of the
      science indicates that we now have sufficient understanding to develop and
      implement a more efficient approach to VOC control policy that will promote
      smarter, more cost-effective VOC controls. Furthermore, the U.S. Environmental
      Protection Agency's recently published Interim Guidance on Control of Volatile
      Organic Compounds in Ozone State Implementation Plans "encourages States to
      consider recent scientific information on the photochemical reactivity of
      volatile organic compounds (VOC) in the development of State implementation plans
      (SIPs)." As has been demonstrated by the California Air Resources Board's Aerosol
      Coatings Rule and the recent experience in Houston addressing high-reactivity
      VOCs, reactivity-based regulations may be more effective and efficient than mass
      based rules in many applications. It is time for regulators, industry, and other
      stakeholders to work togetherto accelerate efforts to bring about a new paradigm
      in VOC control, in which the focus is on the ozone-forming potential of VOC
      emissions, rather than the mass of VOCs emitted.

PMID- 16955877
TI  - Regional public health cost estimates of contaminated coastal waters: a case
      study of gastroenteritis at southern California beaches.
AB  - We present estimates of annual public health impacts, both illnesses and cost of
      illness, attributable to excess gastrointestinal illnesses caused by swimming in
      contaminated coastal waters at beaches in southern California. Beach-specific
      enterococci densities are used as inputs to two epidemiological dose-response
      models to predict the risk of gastrointestinal illness at 28 beaches spanning 160
      km of coastline in Los Angeles and Orange Counties. We use attendance data along
      with the health cost of gastrointestinal illness to estimate the number of
      illnesses among swimmers and their likely economic impact. We estimate that
      between 627,800 and 1,479,200 excess gastrointestinal illnesses occur at beaches
      in Los Angeles and Orange Counties each year. Using a conservative health cost of
      gastroenteritis, this corresponds to an annual economic loss of dollars 21 or
      dollars 51 million depending upon the underlying epidemiological model used (in
      year 2000 dollars). Results demonstrate that improving coastal water quality
      could result in a reduction of gastrointestinal illnesses locally and a
      concurrent savings in expenditures on related health care costs.

PMID- 16955878
TI  - Exceeding of Henry's law by hydrogen peroxide associated with urban aerosols.
AB  - Simultaneous measurements of gas- and aerosol-phase hydrogen peroxide (H2O2) have
      been made at two sites in Los Angeles, one near the Pacific coast at the
      University of California at Los Angeles (UCLA), and the other in downtown Los
      Angeles with close proximity to a heavily traveled freeway (freeway site). At
      both the freeway and UCLA sites, gas-phase H2O2 levels were similar, averaging
      1.17 +/- 1.0 and 1.05 +/- 0.6 ppb, respectively. The particle-associated H2O2 in
      both fine (PM2.5) and coarse (>PM2.5) modes was higher at the freeway site, as
      compared to UCLA, by a factor of 2. However, when aerosol-phase H2O2 is
      normalized to particle mass loadings, the fine-mode H2O2 levels are very similar
      at the two sites: 0.42 +/- 0.3 and 0.58 +/- 0.3 ng H2O2/microg particle mass at
      the freeway and UCLA sites, respectively. The normalized coarse-mode H2O2 levels
      were significantly higher at the freeway site than at UCLA, 1.05 +/- 0.3 and 0.51
      +/- 0.3 ng/microg, respectively. Estimating aerosol liquid water content on the
      basis of relative humidity and aerosol mass, a calculated equivalent H2O2 in
      aerosol liquid water averages 70 mM, more than 2 orders of magnitude higher than
      concentrations predicted by gas-particle partitioning (Henry's law), which
      averages 0.1 mM. This indicates that the sampled particles are capable of
      generating H2O2 in aqueous solution. These corresponding aqueous-phase H2O2
      concentrations in aerosol liquid water exceed levels that have been observed to
      produce cellular damage to lung epithelial cells in laboratory experiments by at
      least 3 orders of magnitude. Although most measurements of H2O2 in particles were
      made using an extraction solution adjusted to pH 3.5, a set of measurements
      indicates that H2O2 from fine-mode particles extracted in the physiologically
      relevant pH range 5-7.5 also generate H2O2 with only slightly lowered efficiency;
      coarse-mode H2O2 production dropped by 75% at the upper end of this range.
      Finally, a small set of measurements was performed to investigate the degree to
      which the recently developed Versatile Aerosol Concentrator Enrichment System
      (VACES) affects H2O2 levels in concentrated ambient aerosols. The VACES appeared
      to a have minimal impact on particulate H2O2.

PMID- 16955879
TI  - Toward a global network for persistent organic pollutants in air: results from
      the GAPS study.
AB  - The Global Atmospheric Passive Sampling (GAPS) study aims to demonstrate the
      feasibility of using passive samplers to assess the spatial distribution of
      persistent organic pollutants on a worldwide basis. The GAPS network includes
      more than 40 sites on 7 continents, mainly in background locations, with some
      representation of urban and agricultural areas. Here we present concentrations of
      organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and
      polybrominated diphenyl ethers (PBDEs) in polyurethane foam disk samplers,
      deployed from December 2004 to March 2005. Legacy OCPs such as alpha-HCH
      (hexachlorocyclohexane), Chlordanes (trans- and cis-Chlordane and trans
      Nonachlor), Dieldrin, and dichlorodiphenyltrichloroethane isomers were detected
      at most sites with some high values that may be related to possible continued use
      and/or re-emissions related to historic use. Geometric mean (GM) air
      concentrations (pg/m3) were: 8.5 for sigmaHCH (sum of alpha- and gamma-isomers),
      2.6 for sigmaChlordanes, 0.8 for Dieldrin, and 0.8 for p,p'-DDE. Current-use
      pesticides such as gamma-HCH (lindane) and especially Endosulfan I exhibited more
      variable and higher concentrations with GMs of 5 and 58, respectively. PCBs and
      PBDEs were elevated at urban/suburban sites consistent with their historical use
      pattern. GM concentrations (pg/m3) were 17 for PCBs and 4 for PBDEs. Sampling
      under GAPS will continue and will eventually allow seasonality effects and longer
      term temporal and spatial trends to be evaluated.

PMID- 16955880
TI  - Mineralogy and characterization of arsenic, iron, and lead in a mine waste
      derived fertilizer.
AB  - The solid-state speciation of arsenic (As), iron (Fe), and lead (Pb) was studied
      in the mine waste-derived fertilizer Ironite using X-ray absorption spectroscopy,
      Mossbauer spectroscopy, and aging studies. Arsenic was primarily associated with
      ferrihydrite (60-70%), with the remainder found in arsenopyrite (30-40%). Lead
      was observed almost exclusively as anglesite (PbSO4), with <1% observed as galena
      (PbS). The identification of As in oxidized Fe oxides and Pb as PbSO4 is in
      disagreement with the dominant reduced phases previously reported and suggests As
      and Pb contained within the mine waste-derived product are more bioavailable than
      previously considered. Aging studies in solution result in Ironite granules
      separating into two distinct fractions, an orange oxide precipitate and a
      crystalline fraction with a metallic luster. The orange oxide fraction contained
      As adsorbed/precipitated with ferrihydrite that is released into solution when
      allowed to equilibrate with water. The fraction with a metallic luster contained
      pyrite and arsenopyrite. A complete breakdown of arsenopyrite was observed in
      Ironite aged for 1 month in buffered deionized water. The observations from this
      study indicate As and Pb exist as oxidized phases that likely develop from the
      beneficiation and processing of mine tailings for commercial sale. The potential
      release of As and Pb has important implications for water quality standards and
      human health. Of particular concern is the quantity of As released from mine
      waste-derived products due to the new As regulation applied in 2006, limiting As
      levels to 10 microg L(-1) in drinking water.

PMID- 16955881
TI  - Aerosol-borne quinones and reactive oxygen species generation by particulate
      matter extracts.
AB  - The mass loadings of quinones and their ability to generate reactive oxygen
      species (ROS) were investigated in total suspended particulate samples collected
      in Fresno, CA, over a 12-month period. Particles were collected on Teflon filters
      and were analyzed for the presence of 12 quinones containing one to four aromatic
      rings by gas chromatography with mass spectrometry. Measured levels are generally
      greater than mass loadings reported at other locations. The mass loadings were
      highest during winter months and were strongly anticorrelated with temperature.
      ROS generation was investigated by measuring the rate of hydrogen peroxide
      production from the reaction of laboratory standards and ambient samples with
      dithiothreitol (DTT). ROS generation from ambient samples shows a strong positive
      correlation with the mass loadings of the three most reactive quinones and may
      account for all of the ROS formed in the DTT test.

PMID- 16955882
TI  - Dissolved free and combined amino acids in surface runoff and drainage waters
      from drained and undrained grassland under different fertilizer management.
AB  - Organic matter is a valuable resource on which the sustainability and
      productivity of soils relies heavily. Thus, it is important to understand the
      mechanisms for the loss of organic compounds from soil. It is also essential to
      determine how these losses can be minimized, especially those resulting from
      anthropogenic activity. Grazed grassland lysimeters (1 hectare) were used to
      examine the contribution and distribution patterns of dissolved free and combined
      amino acids to dissolved organic nitrogen and carbon in surface runoff and
      drainage waters from a grassland soil over three winter drainage periods. The
      waters were collected from soils beneath drained and undrained permanent ryegrass
      swards, receiving 0 and 280 kg ha(-1) year(-1) mineral nitrogen (N) input. Total
      dissolved free amino acid (DFAA) and dissolved combined amino acid (DCAA)
      concentrations ranged between 1.9 nM and 6.1 microM and between 1.3 and 87
      microM, respectively. Although addition of mineral N fertilizer increased both
      DFAA and DCAA concentrations in waters, there was no detectable effect of soil
      hydrology or fertilizer addition on distribution patterns.

PMID- 16955883
TI  - Steroid estrogens, nonylphenol ethoxylate metabolites, and other wastewater
      contaminants in groundwater affected by a residential septic system on Cape Cod,
      MA.
AB  - Septic systems serve approximately 25% of U.S. households and may be an important
      source of estrogenic and other organic wastewater contaminants (OWC) to
      groundwater. We monitored several estrogenic OWC, including nonylphenol (NP),
      nonylphenol mono- and diethoxycarboxylates (NP1EC and NP2EC), the steroid
      hormones 17beta-estradiol (E2), estrone (E1) and their glucuronide and sulfate
      conjugates, and other OWC such as methylene blue active substances (MBAS),
      caffeine and its degradation product paraxanthine, and two fluorescent whitening
      agents in a residential septic system and in downgradient groundwater. E1 and E2
      were present predominantly as free estrogens in groundwater, and near-source
      groundwater concentrations of all OWC were highest in the suboxic to anoxic
      portion of the wastewater plume, where concentrations of most OWC were similar to
      those observed in the septic tank on the same day. NP and NP2EC were up to 6- to
      30-fold higher, and caffeine and paraxanthine were each 60-fold lower than septic
      tank concentrations, suggesting net production and removal, respectively, of
      these constituents. At the most shallow, oxic depth, concentrations of all OWC
      except for NP2EC were substantially lower than in the tank and in deeper wells.
      Yet boron, specific conductance, and the sum of nitrate-and ammonia-nitrogen were
      highest at this shallow depth, suggesting preferential losses of OWC along the
      more oxic flow lines. As far as 6.0 m downgradient, concentrations of many OWC
      were within a factor of 2 of near-source concentrations. The results suggest that
      there is the potential for migration of these OWC, which are unregulated and not
      routinely monitored, in groundwater.

PMID- 16955884
TI  - Increase in rice grain arsenic for regions of Bangladesh irrigating paddies with
      elevated arsenic in groundwaters.
AB  - Concern has been raised by Bangladeshi and international scientists about
      elevated levels of arsenic in Bengali food, particularly in rice grain. This is
      the first inclusive food market-basket survey from Bangladesh, which addresses
      the speciation and concentration of arsenic in rice, vegetables, pulses, and
      spices. Three hundred thirty aman and boro rice, 94 vegetables, and 50 pulse and
      spice samples were analyzed for total arsenic, using inductivity coupled plasma
      mass spectrometry (ICP-MS). The districts with the highest mean arsenic rice
      grain levels were all from southwestern Bangladesh: Faridpur (boro) 0.51 >
      Satkhira (boro) 0.38 > Satkhira (aman) 0.36 > Chuadanga (boro) 0.32 > Meherpur
      (boro) 0.29 microg As g(-1). The vast majority of food ingested arsenic in
      Bangladesh diets was found to be inorganic; with the predominant species detected
      in Bangladesh rice being arsenite (AsIII) or arsenate (AsV) with dimethyl arsinic
      acid (DMAV) being a minor component. Vegetables, pulses, and spices are less
      important to total arsenic intake than water and rice. Predicted inorganic
      arsenic intake from rice is modeled with the equivalent intake from drinking
      water for a typical Bangladesh diet. Daily consumption of rice with a total
      arsenic level of 0.08 microg As g(-1) would be equivalent to a drinking water
      arsenic level of 10 microg L(-1).

PMID- 16955885
TI  - Organochlorine pesticide and polychlorinated biphenyl concentrations in snow,
      snowmelt, and runoff at Bow Lake, Alberta.
AB  - We present analyses of the concentrations of organochlorine (OC) contaminants
      (including organochlorine pesticides and PCBs) in snow, snowmelt, and runoff in
      glacier and snowmelt fed streams at Bow Lake, Alberta in two contrasting
      hydrological years (1997 and 1998). The study investigates the variability in OC
      burdens in snow across the catchment, the elution of OCs from the snowpack, and
      the relationship between OC concentrations in streams and the annual snowpack.
      Snowpacks in forested sites were thinner and had lower OC concentrations than
      snowpacks in open or sparsely vegetated sites. The first snowmelt samples
      exhibited very high contaminant concentrations relative to the snowpack, and even
      the more hydrophobic compounds (Dieldrin, DDTs, and PCBs) were highly
      concentrated in meltwater. Interannual changes in the mean OC concentrations in
      streams did not reflect year-to-year changes in the snowpack contaminant
      concentrations. The results indicate that the extent of glacial ice melt may be
      more important than mean snowpack burdens as a control on OC concentrations in
      runoff in glacial catchments.

PMID- 16955886
TI  - Perfluorinated contaminants in sediments and aquatic organisms collected from
      shallow water and tidal flat areas of the Ariake Sea, Japan: environmental fate
      of perfluorooctane sulfonate in aquatic ecosystems.
AB  - Perfluorinated compounds (PFCs), such as perfluorooctane sulfonate (PFOS),
      perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorohexane sulfonate
      (PFHS), and perfluorooctane sulfonamide (PFOSA) are widely distributed in aquatic
      ecosystems. Despite studies reporting the occurrence of PFCs in aquatic
      organisms, the fate of PFCs in tidal flat and marine coastal ecosystems is not
      known. In this study, we determined concentrations of PFOS, PFOA, PFNA, PFHS, and
      PFOSA in sediments; benthic organisms, including lugworm, mussel, crab, clam,
      oyster, and mudskipper fish from tidal flat; and shallow water species, such as
      filefish, bream, flounder, shark, finless porpoise, gull, and mallard collected
      from the Ariake Sea, Japan. PFOS and PFOA were detected in most of the samples
      analyzed, followed by PFNA, PFOSA, and PFHS. In shallow water species, PFOS was
      the dominant contaminant, and elevated concentrations were found in higher
      trophic level species, such as marine mammals and omnivorous birds. These results
      suggest biomagnification of PFOS through the coastal food chain. In contrast,
      PFOA was the most abundant compound in tidal flat organisms and sediments. PFOA
      concentrations in sediments, lugworms, and omnivorous mudskippers in tidal flat
      were approximately 1 order of magnitude greater than the levels of PFOS. This
      indicates differences in exposure pattern and bioavailability of PFOS and PFOA
      between shallow water and tidal flat organisms. The accumulation profiles of PFCs
      were compared with those of organochlorines (polychlorinated biphenyls, PCB),
      organotin (tributyltin,TBT), and polycyclic aromatic hydrocarbons (PAHs) in tidal
      flat and shallow water samples collected from the Ariake Sea. Concentrations of
      PFCs in sediments and in tidal flat organisms were significantly lower than that
      found for PCBs, TBT, and PAHs. Nevertheless, PFOS concentrations in shallow water
      species were comparable to and/or significantly greater than those of other
      classes of contaminants. This implies that the aqueous phase is a major sink for
      PFCs, which is different from what was observed for nonpolar organic pollutants.

PMID- 16955887
TI  - Atmospheric deposition and marine sedimentation fluxes of polycyclic aromatic
      hydrocarbons in the Eastern Mediterranean Basin.
AB  - Atmospheric input was studied and found to be the major source of PAHs in the
      eastern Mediterranean open marine ecosystem. Dry and wet atmospheric deposition,
      air-sea exchange, and sediment trap fluxes of polycyclic aromatic hydrocarbons
      (PAHs) in the eastern Mediterranean basin were estimated from November 2000 to
      July 2002. Seven dry and four wet deposition samples were analyzed in total and
      PAH concentrations were determined. Airsea exchange fluxes based on air-water
      concentration gradientwere drawn from five air and water samples collected
      concurrently from a coastal area in the eastern Mediterranean. Total annual
      average deposition fluxes of dry, wet, and air-sea exchange sigma35PAHs were
      58.0, 165.7, and -706.4 microg m(-2) y(-1), respectively. Only 1.1 and 0.7% of
      the total atmospheric deposition flux of PAHs was measured in the sediment traps
      at 280 and 1440 m depth, respectively.

PMID- 16955888
TI  - Codeposition of organic carbon and arsenic in Bengal Delta aquifers.
AB  - We present data showing that arsenic (As) was codeposited with organic carbon
      (OC) in Bengal Delta sediments as As and OC concentrations are highly (p < 0.001)
      positively correlated in core profiles collected from widely dispersed
      geographical sites with different sedimentary depositional histories. Analysis of
      modern day depositional environments revealed that the As-OC correlations
      observed in cores are due to As retention and high OC inputs in vegetated zones
      of the deltaic environment. We hypothesize that elevated concentrations of As
      occur in vegetated wetland sediments due to concentration and retention of
      arsenate in aerated root zones and animal burrows where copious iron(III) oxides
      are deposited. On burial of the sediment, degradation of organic carbon from
      plant and animal biomass detritus provides the reducing conditions to dissolve
      iron(III) oxides and release arsenite into the porewater. As tubewell abstracted
      aquifer water is an invaluable resource on which much of Southeast Asia is now
      dependent, this increased understanding of the processes responsible for As
      buildup and release will identify, through knowledge of the palaeosedimentary
      environment, which sediments are at most risk of having high arsenic
      concentrations in porewater. Our data allow the development of a new unifying
      hypothesis of how As is mobilized into groundwaters in river flood plains and
      deltas of Southeast Asia, namely that in these highly biologically productive
      environments, As and OC are codeposited, and the codeposited OC drives As release
      from the sediments.

PMID- 16955889
TI  - Effect of in ovo exposure to PCBs and Hg on Clapper Rail bone mineral chemistry
      from a contaminated salt marsh in coastal Georgia.
AB  - The effect of Hg and PCBs (Aroclor 1268) on bone characteristics was investigated
      in a population of Clapper Rails (Rallus longirostris) inhabiting contaminated
      and unimpacted estuarine marsh systems in coastal Georgia. Exposure to
      contaminants did not affect the length or weight of leg bones, but it
      significantly altered the chemical composition of the bone. Specifically, bone in
      the contaminated site had a higher Ca to P, and lower carbonate and acid
      phosphate content. These characteristics are typical of more mature bone mineral
      and indicate that toxicants have accelerated bone maturation. FTIR spectroscopy
      data revealed a dose dependent change in the crystallinity of bone mineral, and
      the relative proportion of specific PO4 groups in different molecular
      environments in the bone, with toxicants loads. These changes are most probably
      related to a hormonal alteration of the rate of bone remodelation induced by
      exposure to toxicant loads.

PMID- 16955890
TI  - Association between perfluorinated compounds and pathological conditions in
      southern sea otters.
AB  - Concentrations of four perfluorinated contaminants, including
      perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA), were measured
      in liver tissue from 80 adult female sea otters collected from the California
      coast during 1992-2002. Concentrations of PFOS and PFOA were in the ranges of <1
      884 and <5-147 ng/g, wet wt, respectively. Concentrations of PFOA in the livers
      of these sea otters were among the highest values reported for marine mammals to
      date. Liver tissue from 6 male sea otters also was analyzed and contained
      significantly higher concentrations of PFOS than did tissues from female otters.
      To examine the association between exposures and potential effects,
      concentrations of PFOS and PFOA were compared among the adult female otters that
      died from infectious diseases, noninfectious causes, and from apparent
      emaciation. Concentrations of both PFOA and PFOS were significantly higher in sea
      otters in the infectious disease category than in the noninfectious category.
      Concentrations of PFOS and PFOA were not significantly different between
      noninfectious and emaciated otters, suggesting that the poor nutritive (body)
      status of emaciated otters did not affectthe concentrations of perfluorochemicals
      in livers. Concentrations of PFOA increased significantly from 1992 to 2002,
      whereas PFOS concentrations increased from 1992to 1998 and then decreased after
      2000. Significant association between infectious diseases and elevated
      concentrations of PFOS/PFOA in the livers of sea otters is a cause for concern
      and suggests the need for further studies.

PMID- 16955891
TI  - Characteristics of SME biodiesel-fueled diesel particle emissions and the
      kinetics of oxidation.
AB  - Biodiesel is one of the most promising alternative diesel fuels. As diesel
      emission regulations have become more stringent, the diesel particulate filter
      (DPF) has become an essential part of the aftertreatment system. Knowledge of
      kinetics of exhaust particle oxidation for alternative diesel fuels is useful in
      estimating the change in regeneration behavior of a DPF with such fuels. This
      study examines the characteristics of diesel particulate emissions as well as
      kinetics of particle oxidation using a 1996 John Deere T04045TF250 off-highway
      engine and 100% soy methyl ester (SME) biodiesel (B100) as fuel. Compared to
      standard D2 fuel, this B100 reduced particle size, number, and volume in the
      accumulation mode where most of the particle mass is found. At 75% load, number
      decreased by 38%, DGN decreased from 80 to 62 nm, and volume decreased by 82%.
      Part of this decrease is likely associated with the fact that the particles were
      more easily oxidized. Arrhenius parameters for the biodiesel fuel showed a 2
      3times greater frequency factor and approximately 6 times higher oxidation rate
      compared to regular diesel fuel in the range of 700-825 degrees C. The faster
      oxidation kinetics should facilitate regeneration when used with a DPF.

PMID- 16955892
TI  - Evidence for oligomer formation in clouds: reactions of isoprene oxidation
      products.
AB  - Electrospray ionization mass spectrometry (ESI-MS) was used to investigate
      product formation in laboratory experiments designed to study secondary organic
      aerosol (SOA) formation in clouds. It has been proposed that water soluble
      aldehydes derived from aromatics and alkenes, including isoprene, oxidize further
      in cloud droplets forming organic acids and, upon droplet evaporation, SOA.
      Pyruvic acid is an important aqueous-phase intermediate. Time series samples from
      photochemical batch aqueous phase reactions of pyruvic acid and hydrogen peroxide
      were analyzed for product formation. In addition to the monomers predicted by the
      reaction scheme, products consistent with an oligomer system were found when
      pyruvic acid and OH radical were both present. No evidence of oligomer formation
      was found in a standard mix composed of pyruvic, glyoxylic, and oxalic acids
      prepared in the same matrix as the samples analyzed using the same instrument
      conditions. The distribution of high molecular weight products is consistent with
      oligomers composed of the mono-, oxo-, and di-carboxylic acids expected from the
      proposed reaction scheme.

PMID- 16955893
TI  - Coprecipitation of arsenate with metal oxides: nature, mineralogy, and reactivity
      of aluminum precipitates.
AB  - Arsenic mobilization in soils is mainly controlled by sorption/desorption
      processes, but arsenic also may be coprecipitated with aluminum and/or iron in
      natural environments. Although coprecipitation of arsenic with aluminum and iron
      oxides is an effective treatment process for arsenic removal from drinking water,
      the nature and reactivity of aluminum- or iron-arsenic coprecipitates has
      received little attention. We studied the mineralogy, chemical composition, and
      surface properties of aluminum-arsenate coprecipitates, as well as the sorption
      of phosphate on and the loss of arsenate from these precipitates. Aluminum
      arsenate coprecipitates were synthesized at pH 4.0, 7.0, or 10.0 and As/Al molar
      ratio (R) of 0, 0.01, or 0.1 and were aged 30 or 210 d at 50 degrees C. In the
      absence of arsenate, gibbsite (pH 4.0 or 7.0) and bayerite (pH 10.0) formed,
      whereas in the presence of arsenate, very poorly crystalline precipitates formed.
      Short-range ordered materials (mainly poorly crystalline boehmite) formed at pH
      4.0 (R = 0.01 and 0.1), 7.0, and 10.0 (R= 0.1) and did not transform into Al(OH)3
      polymorphs even after prolonged aging. The surface properties and chemical
      composition of the aluminum precipitates were affected by the initial pH, R, and
      aging. Chemical dissolution of the samples by 6 mol L(-1) HCl and 0.2 mol L(-1)
      oxalic acid/ oxalate solution indicated that arsenate was present mainly in the
      short-range ordered precipitates. The sorption of phosphate onto the precipitates
      was influenced by the nature of the samples and the amounts of arsenate present
      in the precipitates. Large amounts of phosphate partially replaced arsenate only
      from the samples formed at R = 0.1. The quantities of arsenate desorbed from
      these coprecipitates by phosphate increased with increasing phosphate
      concentration, reaction time, and precipitate age butwere always lessthan 30% of
      the amounts of arsenate present in the materials and were particularly low (<4%)
      from the sample prepared at pH 4.0. Arsenate appeared to be occluded within the
      network of short-range ordered materials and/or sorbed onto the external surfaces
      of the precipitates, but sorption on the external surfaces seemed to increase by
      increasing pH of sample preparation and aging. Furthermore, at pH 4.0 more than
      in neutral or alkaline systems the formation of aluminum arsenate precipitates
      seemed to be favored. Finally, we have observed that greater amounts of phosphate
      were sorbed on an aluminum-arsenate coprecipitate than on a preformed aluminum
      oxide equilibrated with arsenate under the same conditions (R = 0.1, pH 7.0). In
      contrast, the opposite occurred for arsenate desorption, which was attributed to
      the larger amounts of arsenate occluded in the coprecipitate.

PMID- 16955894
TI  - Emission of PCDD/F, PCB, and HCB from combustion of firewood and pellets in
      residential stoves and boilers.
AB  - To assess potential emissions of polychlorinated dibenzo-p-dioxins (PCDDs),
      polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), and
      hexachlorobenzene (HCB) from residential combustion of biofuels, experiments were
      performed in which various types of pellets and firewood were combusted in four
      types of stoves and boilers, with both full and reduced rates of air supply.
      Intermittent combustion of wood pellets resulted in emissions of 11 ng-(WHO
      TEQ)/kg combusted fuel (dry weight). A modern, environmentally certified boiler
      yielded somewhat lower emissions of PCCD/F and PCB than a wood stove. Both gave
      <0.1 ng(WHO-TEQ)/m3n (1.3-6.5 ng(WHO-TEQ)/kg) and considerably lower emissions
      than an old boiler (7.0-13 ng(WHO-TEQ)/kg). No positive effect on emissions could
      be observed in full air combustion (simulating the use of a heat storage tank)
      compared to combustion with reduced air. Two of the wood combustion experiments
      included paper and plastic waste fuels. Chlorine-containing plastic waste gave
      rise to high emissions: ca. 310 ng(WHO-TEQ)/ kg over the whole combustion cycle.
      The homologue profiles of PCDD/Fs show characteristic differences between ashes
      and flue gas from combustions with different levels of air supply. These
      differences do not, however, seem to have any correlation to the relative amount
      of toxic congeners.

PMID- 16955895
TI  - QSAR study of the reduction of nitroaromatics by Fe(II) species.
AB  - The development of predictive models for the reductive transformation of
      nitroaromatics requires further clarification of the effect of environmentally
      relevant variables on reaction kinetics and the identification of readily
      available molecular descriptors for calculating reactivity. Toward these goals,
      studies were performed on the reduction of a series of monosubstituted
      nitrobenzenes in Fe(II)-treated goethite suspensions. The energy of the lowest
      unoccupied molecular orbital, ELUMO (B3LYP/6-31G*,water), of the nitrobenzenes
      was capable of explaining 99% of the variability in the rates. Results of
      experiments in which the surface area loading of ferric oxides was systematically
      varied indicate that (i) the reactivity of mineral-surface-associated Fe(II),
      Fe(II)surf, toward the reduction of p-cyanonitrobenzene (CNNB) decreased in the
      order hematite > goethite > lepidocrocite > ferrihydrite and (ii) the surface
      density of Fe(II)surf did not play a crucial role in determining the observed
      reactivity trend. CNNB was reduced in Fe(II)-only control experiments in a pH
      range of 7.28-7.97 with a pH dependency consistent with the transformation of
      Fe(II) to Fe(OH)3 or related oxides. The pH dependency of the reduction of CNNB
      in Fe(II)-treated ferric oxide suspensions (pH 6.1-7.97) could be accounted for
      by the oxidation of Fe(II)surf, forming an Fe(III) oxide.

PMID- 16955896
TI  - Water-soluble oligomer formation from acid-catalyzed reactions of levoglucosan in
      proxies of atmospheric aqueous aerosols.
AB  - Herein is reported the first laboratory observation of the oligomerization of
      levoglucosan studied under atmospherically relevant conditions. Oligomers up to
      1458 Da (9-mer) were measured by matrix-assisted laser desorption ionization time
      of-flight mass spectrometry. A rational mechanism is proposed based on both the
      acid-catalyzed cationic ring-opening of levoglucosan and nucleophilic attack of
      ROH from levoglucosan on the hemi-acetal carbon to produce pyranose oligomers
      through the formation of glycosidic bonds. Oligomer formation is further
      supported by attenuated total reflectance Fourier transform infrared
      spectroscopy. Levoglucosan is a viable tracer for biomass burning aerosols, and
      the observed products may serve as secondary tracers for these types of aerosols,
      possibly providing additional information to facilitate source apportionment and
      better understand atmospheric processing of the aerosol parcel. Also, the
      processes supported here may contribute to the saccharide character of humic-like
      substances, which are proposed to be formed through the atmospheric processing of
      biomass burning aerosols.

PMID- 16955897
TI  - Variability of indicator bacteria at different time scales in the Upper Hoosic
      River watershed.
AB  - Accurately evaluating whether a water body is meeting water quality criteria for
      indicator bacteria requires an understanding of the spatial and temporal
      variability in concentrations of these indicators. We have collected data on
      concentrations of Escherichia coli at 12 sites within the upper Hoosic River
      Basin, spanning a range of land uses and levels of development. Sampling was
      conducted with the goal of assessing the variation in E. coli levels over
      different time scales: seasonal, storm-related, and diurnal. General linear
      models were constructed to describe the factors contributing to E. coli
      concentrations at a given location and time. We found that bacterial levels were
      higher in more developed watersheds; in summer rather than winter; in storms
      rather than baseflow; and in the early morning rather than afternoon. Seasonal
      and storm sampling captured different portions of the range of E. coli
      concentrations, but the levels of variability at these two scales were similar.
      Diurnal sampling produced concentrations intermediate between seasonal and storm
      sampling. Compared to a pristine stream, a more urbanized stream exhibited
      greater diurnal variability, but less variation from baseflow to stormflow. We
      recommend collecting both seasonal and storm data, but not necessarily diurnal
      data, in assessment of stream bacterial quality.

PMID- 16955898
TI  - Persistence of Klebsiella pneumoniae on simulated biofilm in a model drinking
      water system.
AB  - Persistence of Klebsiella pneumoniae on corroded iron surfaces in drinking water
      was studied using biofilm annular reactors operated under oligotrophic
      conditions. Reactors were inoculated with K. pneumoniae, and persistence was
      monitored in the bulk and biofilm phases. Initial cell concentration of 10(6)
      MPN/mL in the bulkwater phase resulted in significantly longer adhesion than
      initial concentrations 1 and 2 orders of magnitude lower. K. pneumoniae cultured
      in low nutrient growth medium persisted longer in dechlorinated tap water than
      those cultured in full strength medium. Cell surface charge was more negative
      under low nutrient conditions, and this influenced electrostatic attraction
      between the cells and the oxidized iron surface. Cells grown in full strength
      media persisted longer in water with both low (<0.2 mg/L) and high (>0.5 mg/L)
      free chlorine residuals. Growth media injected with the cells dechlorinated the
      water allowing adhesion without inactivation. Microelectrode measurements showed
      a 40-70% drop in free chlorine from the bulk to the coupon surface, which
      decreased disinfectant potency against adhered cells. Growth and injection
      conditions clearly influenced cell adhesion and persistence, but permanent
      colonization of the corroded iron surface by K. pneumoniae was not observed.

PMID- 16955899
TI  - Reduction of uranyl in the interlayer region of low iron micas under anoxic and
      aerobic conditions.
AB  - The role of the interlayer region of three different FeII-poor micas (2.8,
      approximately 0.02, and 0.01 FeII atom %) in the reduction of UVI was
      investigated at pH approximately 4.3, low ionic strength, and 23 degrees C under
      both anoxic and aerated conditions in batch reactors for 1 to 10 days. U
      diffusion profiles were mapped with X-ray microscopy, and the oxidation state of
      U was tracked with XANES as a function of distance from the crystal edge. Peak U
      concentrations only reached about 0.006-0.0002 atom percent, where the full-width
      at-half-maximums of the diffusion fronts were roughly 25-50 microm. Results for
      anoxic conditions indicated appreciable reduction of uranyl in all three micas
      with no measurable dependency on distance from the edge. Under aerobic (open to
      the atmosphere) conditions, U was still partially reduced, although to a lesser
      degree than for anoxic conditions, and UVI/Utot increased with time.
      Interestingly, reoxidation reached a plateau after about 3-10 days, leaving an
      appreciable proportion of U reduced. It is likely that measurable reduction
      occurred, despite low FeII, because U concentrations were even lower, where
      FeII/U ratios ranged from about 10(4)-10(2). A coupled diffusion-reduction model
      was developed that successfully simulated the proximal portion of the diffusion
      front. The results show that reduction of UVI in the interlayer of low FeII micas
      is, in principle, viable and that under aerobic conditions reduction is initially
      faster than reoxidation. This extends the range of possible environments where
      heterogeneous reduction of UVI by micas might occur.

PMID- 16955900
TI  - Localizing the biochemical transformations of arsenate in a hyperaccumulating
      fern.
AB  - The fern Pteris vittata accumulates unusually high levels of arsenic. Using X-ray
      absorption spectroscopy (XAS) and XAS imaging, we reveal the distribution of
      arsenic species in vivo. Arsenate is transported through the vascular tissue from
      the roots to the fronds (leaves), where it is reduced to arsenite and stored at
      high concentrations. Arsenic-thiolate species surrounding veins may be
      intermediates in this reduction. In gametophytes, arsenite is compartmentalized
      within the cell vacuole. Arsenic is excluded from cell walls, rhizoids, and
      reproductive areas. This study provides important insights into arsenic
      hyperaccumulation, which may prove useful for phytoremediating arsenic
      contaminated sites, and demonstrates the strengths of XAS imaging for
      distinguishing highly localized species.

PMID- 16955901
TI  - Observed and simulated fluid drag effects on colloid deposition in the presence
      of an energy barrier in an impinging jet system.
AB  - The deposition and re-entrainment behaviors of carboxylate-modified latex
      microspheres (0.2-, 0.5-, 1.0-, and 2.0-microm diameter) were examined in an
      impinging jet system on both glass and quartz substrata under a variety of
      environmentally relevant fluid velocities (2.12 x 10(-4) to 1.06 x 10(-3) m sec(
      1)) in both the absence and the presence of an energy barrier to deposition. In
      the absence of an energy barrierto deposition, deposition fluxes onto glass and
      quartz substrata increased with increasing fluid velocity for all four
      microsphere sizes, in accordance with expectations from theory. In contrast, in
      the presence of an energy barrier to deposition, deposition efficiencies onto
      glass and quartz substrata decreased with increasing fluid velocity for all four
      microsphere sizes. Lack of re-entrainment and observed strong attachment were
      consistent with the expectation that deposition occurs via the primary energy
      minima where nanoscale surface heterogeneity locally reduces or eliminates the
      energy barrier to deposition. Colloid deposition onto an overall opposite-charged
      surface was simulated using a particle transport model with randomly distributed
      hetero domains that were like-charged relative to the colloid. Varying the size
      and number of the hetero domains showed that simulated colloid deposition
      efficiencies decreased with increasing fluid velocity when the hetero domains
      were small relative to the colloid. The simulations thereby demonstrate that
      observed decreases in colloid deposition efficiencies with increasing fluid
      velocity are consistent with the hypothesis that colloid deposition onto overall
      like-charged surfaces occurs at nanoscale hetero domains where repulsion is
      locally reduced or eliminated.

PMID- 16955902
TI  - Modeling the transport and inactivation of E. coli and enterococci in the near
      shore region of Lake Michigan.
AB  - To investigate the transport and fate of fecal pollution at Great Lakes beaches
      and the health risks associated with swimming, the near-shore waters of Lake
      Michigan and two tributaries discharging into it were examined for bacterial
      indicators of human fecal pollution. The enterococcus human fecal pollution
      marker, which targets a putative virulence factor--the enterococcal surface
      protein (esp) in Enterococcus faecium, was detected in 2/28 samples (7%) in the
      tributaries draining into Lake Michigan and in 6/30 samples (20%) in Lake
      Michigan beaches. This was indicative of human fecal pollution being transported
      in the tributaries and occurrence at Lake Michigan beaches. To understand the
      relative importance of different processes influencing pollution transport and
      inactivation, a finite-element model of surf-zone hydrodynamics (coupled with
      models for temperature, E. coli and enterococci) was used. Enterococci appear to
      survive longer than E. coli, which was described using an overall first-order
      inactivation coefficient in the range 0.5-2.0 per day. Our analysis suggests that
      the majority of fecal indicator bacteria variation can be explained based on
      loadings from the tributaries. Sunlight is a major contributor to inactivation in
      the surf-zone and the formulation based on sunlight, temperature and
      sedimentation is preferred over the first-order inactivation formulation.

PMID- 16955903
TI  - Single-particle detection efficiencies of aerosol time-of-flight mass
      spectrometry during the North Atlantic marine boundary layer experiment.
AB  - During the North Atlantic marine boundary layer experiment (NAMBLEX) sampling
      campaign at Mace Head, Ireland, both continental and maritime air masses were
      sampled. Aerosol was characterized both with a TSI 3800 time-of-flight mass
      spectrometer (ATOFMS) and a MOUDI microorifice impactor, and particle number
      counts were measured independently with an aerodynamic particle sizer. The data
      have been analyzed in order to elucidate factors determining the particle
      detection efficiencies of the ATOFMS. These are broken down according to the
      efficiency of the inlet system, the hit efficiency on particles which enter the
      sensing zone of the instrument and the sensitivity of the measured ion signal to
      the chemical species. A substantial matrix effect depending on the chemical
      composition of the aerosol sampled at the time was found, which is reflected in
      variations in the hit efficiency of particles entering the sensing zone of the
      instrument with the main desorption-ionization laser. This is in addition to the
      strong inverse power-law dependence of inlet transmission efficiency on particle
      diameter. The variation in hit efficiency with particle type is likely
      attributable to differences in the energetics of laser energy absorption,
      ablation, and ion formation. However, once variations in both inlet transmission
      and hit efficiencies are taken into account, no additional matrix dependence of
      ATOFMS response is required to obtain a linear relationship between the ion
      signal and the concentration of a particular chemical species. The observations
      show that a constant mass of material is ionized from each particle, irrespective
      of size. Consequently the integrated ion signal for a given chemical component
      and particle size class needs to be increased by a factor related to the cube of
      particle diameter in order to correlate with the airborne mass of that component.

PMID- 16955904
TI  - Spectrophotometric measurements of pH in-situ: laboratory and field evaluations
      of instrumental performance.
AB  - Automated in-situ instrumentation has been developed for precise and accurate
      measurements of a variety of analytes in natural waters. In this work we describe
      the use of 'SEAS' (spectrophotometric elemental analysis system) instrumentation
      for measurements of solution pH. SEAS-pH incorporates a CCD-based
      spectrophotometer, an incandescent light source, and dual pumps for mixing
      natural water samples with a sulfonephthalein indicator. The SEAS-pH optical cell
      consists of either a liquid core waveguide (LCW, Teflon AF-2400) or a custom-made
      PEEK cell. Long optical path lengths allow use of indicators at low
      concentrations, thereby precluding large indicator-induced pH perturbations.
      Laboratory experiments show that pH measurements obtained using LCW and PEEK
      optical cells are indistinguishable from measurements obtained using conventional
      spectrophotometric cells and high-performance spectrophotometers. Deployments in
      the Equatorial Pacific and the Gulf of Mexico demonstrate that SEAS-pH
      instruments are capable of obtaining vertical pH profiles with high spatial
      resolution. SEAS-pH deployments at a fixed river-site (Hillsborough River, FL)
      demonstrate the capability of SEAS for observations of diel pH cycles with high
      temporal resolution. The in-situ precision of SEAS-pH is assessed as 0.0014 pH
      units, and the system's measurement frequency is approximately 0.5 Hz. This work
      indicates that in-situ instrumentation can be used to provide accurate, precise,
      and highly resolved observations of carbon-system transformations in the natural
      environment.

PMID- 16955905
TI  - A non-perturbing scheme for the mineralogical characterization and quantification
      of inorganic colloids in natural waters.
AB  - Although the role played by inorganic colloids in natural waters depends on their
      composition as well as on their size, the characterization of submicron particles
      has rarely gone beyond describing the morphology and identifying some of the most
      abundant particles. The process of quantification has been hampered by a lack of
      suitable analytical methods. This study demonstrates that it is possible to
      identify and quantify inorganic particles in the colloidal size range by applying
      a straightforward methodology based on a well-proved, quantitative, and
      nonperturbing method of sample preparation (direct centrifugation of the samples
      on transmission electron microscopy grids) in conjunction with particle analysis
      using widely available techniques: transmission electron microscopy, energy
      dispersive X-ray spectroscopy (EDS), and selected area electron diffraction
      (SAED). The method has successfully been applied to six water samples from basins
      of contrasting geological characteristics. The method has the advantage of
      minimizing sample modifications by allowing on site sample preparation, using
      standard equipment, and it is not particularly time-consuming. Notably, the
      combination of EDS and SAED information makes it possible to characterize and
      quantify the most abundant components of the colloidal pool in the majority of
      the aquatic systems: the different types of aluminosilicates.

PMID- 16955906
TI  - Speciation of sulfate in size-fractionated aerosol particles using sulfur K-edge
      X-ray absorption near-edge structure.
AB  - X-ray absorption near-edge structure (XANES) at sulfur K-edge was used to
      determine the sulfate species present in size-fractionated aerosol particles
      based on the postedge structure after the main absorption peak in the XANES
      region. A comparison of the XANES spectra of reference sulfate materials and
      aerosol samples collected in Tsukuba in Japan clearly showed that (NH4)2SO4 was
      the main sulfur species in particles with a smaller diameter and CaSO4 x 2H2O
      (gypsum) was the main sulfur species in particles with a larger diameter. A
      simulation of the XANES spectra by reference materials allows us to obtain the
      quantitative mixing ratios of the different sulfate species present in the
      aerosol samples. The presence of minor sulfur species other than (NH4)2SO4 and
      gypsum at the surface of mineral aerosols is suggested in our simulations and by
      a surface-sensitive conversion electron/He-ion yield XANES. In the absence of a
      contribution from a large dust event, the mole concentration of gypsum in the
      mineral aerosol fraction (particle diameter > 1 microm) determined by XANES is
      similar to that of Ca which is determined independently using ion chromatography.
      This shows that the Ca and sulfate in the mineral aerosols are present only as
      gypsum. Considering that calcite is the main Ca mineral in the original material
      arising from an arid and semiarid area in China, it is strongly suggested that
      gypsum is formed in aerosol during its long-range transportation by a reaction
      between calcite and sulfate ions.

PMID- 16955907
TI  - A counter-current parallel-plate membrane denuder for the non-specific removal of
      trace gases.
AB  - In this paper we present a counter-current parallel-plate membrane diffusion
      denuder for the non-specific removal of trace gases from an air flow. In this
      design, gaseous pollutants are removed by diffusing from a sample channel to two
      purge channels by crossing microporous membranes. In the laboratory, at a sample
      flow rate of 5 L/min and purge flow rates of 5 L/min each, gas removal
      efficiencies ranged from 84% for CO to 72% for SF6. Removal efficiencies
      increased with lower sample flow rate, a higher sample to purge flow rate ratio,
      a longer channel length, and using molecules with higher diffusion coefficient.
      Removal efficiencies were, however, not affected by the sample channel height. In
      addition, gas penetration was exponentially associated with the product of
      channel length, diffusion coefficient, and the inverse of sample flow rate.
      Particle losses were significant (10-25% losses) only for particles smaller than
      50 nm. In a field evaluation, the denuder's performance was tested with an
      aerosol produced in a photochemical chamber. The denuder's performance was
      similar to that observed in the laboratory and was stable over time. Finally, the
      denuder was tested with a semivolatile organic aerosol. Particle mass losses due
      to volatilization were about 30%.

PMID- 16955908
TI  - Evaluation of a newly developed enzyme-linked immunosorbent assay for
      determination of linear alkyl benzenesulfonates in wastewater treatment plants.
AB  - A recently developed enzyme-linked immunosorbent assay (ELISA) for the
      determination of linear alkyl benzenesulfonates (LAS) and long chain sulfophenyl
      carboxylates (SPCs) has been evaluated for its application in wastewater control
      analysis. This ELISA based on the use of polyclonal antibodies in an indirect
      format shows an IC50 of 28.1 +/- 3.2 microg L(-1) and a limit of detection (LOD)
      of 1.8 +/- 0.6 microg L(-1) in buffer. The assay uses antibodies raised through a
      pseudoheterologous immunization strategy using an equimolar mixture of two
      immunogens, N-(4-alkylphenyl)sulfonyl-3-aminopropanoic acid covalently coupled to
      keyhole limped hemocyanin (SFA-KLH) and sulfophenyl carboxylate 13C13 coupled to
      KLH (13C13-SPC-KLH). The immunizing haptens have been designed to address
      recognition versus two different epitopes of the LAS molecule. To assess the
      performance of this immunoassay in complex real samples, a cross reactivity study
      was carried out, and the possible interference of other surfactants commonly
      detected in wastewater, including nonylphenol ethoxylates (NPEOs), nonylphenol
      (NP), octylphenol (OP), and coconut fatty acid diethanol amides (CDEA), have been
      evaluated. Additionally, a study of the matrix effects of different types of
      wastewater was achieved. This ELISA has been evaluated and validated by measuring
      the LAS content of 22 samples collected from the influents and the effluents of
      six wastewater treatment plants (WWTP) located in Catalonia, Spain. A solid-phase
      extraction followed by liquid chromatography coupled to mass spectrometry
      detection (SPE-LC-MS) has been used as a validation method of the new ELISA test.

PMID- 16955909
TI  - Formation of cyclopentadienyl radical from the gas-phase pyrolysis of
      hydroquinone, catechol, and phenol.
AB  - The formation of radicals from the gas-phase pyrolysis of hydroquinone, catechol,
      and phenol over a temperature range of 400-750 degrees C was studied using the
      technique of low-temperature matrix isolation electron paramagnetic resonance
      (LTMI EPR). Cooling the reactor effluent from pyrolysis in a nitrogen carrier gas
      to 77 K produces a cryogenic matrix that exhibits poorly resolved EPR spectra.
      However, using carbon dioxide as a carrier gas formed a matrix that, upon
      annealing by slowly raising the matrix temperature followed by rapid recooling to
      77 K, yielded more resolved, identifiable spectra. Annealed spectra of all three
      samples resulted in the generation of EPR spectra above 700 degrees C with 6
      lines, hyperfine splitting constant approximately 6.0 G, and peak to peak width
      approximately 3 G that was readily assignable, based on comparison to the
      literature and theoretical calculations, as that of cyclopentadienyl radical.
      Pyrolysis at temperatures below 700 degrees C generated a carbon dioxide matrix
      isolation spectrum with a high g-value (>2.0040) that is attributed to oxygen
      containing radicals such as semiquinone or phenoxyl. Conclusive identification of
      anticipated semiquinone, phenoxyl, and hydroxycyclopentadienyl radicals was
      complicated by the ability of these radicals to exist in carbon-centered and
      oxygen-centered resonance structures that can give different EPR spectra.

PMID- 16955910
TI  - Spinel formation for stabilizing simulated nickel-laden sludge with aluminum-rich
      ceramic precursors.
AB  - The feasibility of stabilizing nickel-laden sludge from commonly available Al
      rich ceramic precursors was investigated and accomplished with high nickel
      incorporation efficiency. To simulate the process, nickel oxide was mixed
      alternatively with gamma-alumina, corundum, kaolinite, and mullite and was
      sintered from 800 to 1480 degrees C. The nickel aluminate spinel (NiAl2O4) was
      confirmed as the stabilization phase for nickel and crystallized with
      efficiencies greater than 90% for all precursors above 1250 degrees C and 3-h
      sintering. The nickel-incorporation reaction pathways with these precursors were
      identified, and the microstructure and spinel yield were investigated as a
      function of sintering temperature with fixed sintering time. This study has
      demonstrated a promising process for forming nickel spinel to stabilize nickel
      laden sludge from a wide range of inexpensive ceramic precursors, which may
      provide an avenue for economically blending waste metal sludges via the building
      industry processes to reduce the environmental hazards of toxic metals. The
      correlation of product textures and nickel incorporation efficiencies through
      selection of different precursors also provides the option of tailoring property
      specific products.

PMID- 16955911
TI  - Effects of reformulated gasoline and motor vehicle fleet turnover on emissions
      and ambient concentrations of benzene.
AB  - Gasoline-powered motor vehicles are a major source of toxic air contaminants such
      as benzene. Emissions from light-duty vehicles were measured in a San Francisco
      area highway tunnel during summers 1991, 1994-1997, 1999, 2001, and 2004. Benzene
      emission rates decreased over this time period, with a large (54 +/- 5%) decrease
      observed between 1995 and 1996 when California phase 2 reformulated gasoline
      (RFG) was introduced. We attribute this one-year change in benzene mainly to RFG
      effects: 36% from lower aromatics in gasoline that led to a lower benzene mass
      fraction in vehicle emissions, 14% due to RFG effects on total nonmethane organic
      compound mass emissions, and the remaining 4% due to fleet turnover. Fleet
      turnover effects accumulate over longer time periods: between 1995 and 2004,
      fleet turnover led to a 32% reduction in the benzene emission rate. A
      approximately 4 microg m(-3) decrease in benzene concentrations was observed at a
      network of ambient air sampling sites in the San Francisco Bay area between the
      late 1980s and 2004. The largest decrease in annual average ambient benzene
      concentrations (1.5 +/- 0.7 microg m(-3) or 42 +/- 19%) was observed between 1995
      and 1996. The reduction in ambient benzene between spring/summer months of 1995
      and 1996 due to phase 2 RFG was larger (60 +/- 20%). Effects of fuel changes on
      benzene during fall/winter months are difficult to quantify because some
      wintertime fuel changes had already occurred prior to 1995.

PMID- 16955912
TI  - Investigation of mechanisms of oxidation of EDTA and NTA by permanganate at high
      pH.
AB  - Permanganate has been used for oxidation of nuclear wastes containing chelating
      agents such as ethylenediaminetetraacetic and nitrilotriacetic acids (EDTA and
      NTA) to improve separation of radionuclides and heavy metals from the wastes,
      butthe mechanisms of degradation of these and related organic ligands at high pHs
      have not been studied. EDTA, NTA, and the model compound ethylenediamine (EN)
      were found to be readily oxidized by permanganate at pH 12-14. The reduction of
      permangante was accompanied by formation of unstable manganate and dispersed MnO2
      particles, which constituted the final product of permanganate reduction. The
      yields and speciation of EDTA, NTA, and EN breakdown products were affected by
      the pH and permanganate dose. Iminodiacetic acid (IDA), oxalate, formate, and
      ammonia were the predominant EDTA and NTA oxidation products. Mineralization of
      EDTA, NTA, and EN to CO2 was more significant at pH 12. At pH 14 formation of
      oxalate and deamination to NH3 were the most important reactions. IDA was
      released upon the oxidation of both EDTA and NTA, but EDTA oxidation yielded no
      ethylenediaminediacetic acid (EDDA). The speciation of the reaction products
      indicated that the ethylene group in EDTA was the preferred attack site in
      oxidations by alkaline permanganate.

PMID- 16955913
TI  - Monitoring the removal efficiency of pharmaceuticals and hormones in different
      treatment processes of source-separated urine with bioassays.
AB  - Urine can be collected separately from the general wastewater with the aim of
      recycling the nutrients. Urine source-separation not only prevents wasting
      nutrients but also prevents potentially hazardous micropollutants from entering
      the wastewater stream and tainting a final fertilizer product. We assessed
      various urine treatment technologies for their performance to remove
      micropollutants such as pharmaceuticals, natural and synthetic steroid hormones,
      and their human biotransformation products. Removal efficiencies were determined
      with a combination of bioassays and chemical target analysis. The yeast estrogen
      screen yielded information on estrogenicity. Specific phytotoxicity and
      nonspecific baseline toxicity was determined with an algae chlorophyll
      fluorescence test. Filtration methods, such as nanofiltration and
      electrodialysis, were highly efficient with respect to toxicity reduction.
      Micropollutant degradation during biological treatment in a sequencing batch
      reactor was very compound specific. Ozonation removed the target analytes and the
      estrogenicity completely, but the baseline toxicity was only reduced by 50-60%
      depending on the ozone doses. Struvite precipitation produced a very "clean"
      fertilizer product that is ready to use. The examples show that bioassays and
      chemical analysis yield complementary information, but are very useful to monitor
      treatment efficiencies and to assess the ecotoxicological potential of byproducts
      of urine treatment processes. The results of this study present a method to
      assess the micropollutant removal efficiency, and therefore, support the choice
      of an appropriate urine processing technique for real-world applications.

PMID- 16955914
TI  - Arsenic leaching from mulch made from recycled construction and demolition wood
      and impacts of iron-oxide colorants.
AB  - Mulch made from recycled construction and demolition (C&D) wood has been reported
      to contain elevated levels of arsenic from inadvertent inclusion of chromated
      copper arsenate (CCA)-treated wood. Such mulch is also commonly colored with iron
      oxide, a compound known to bind arsenic. The objectives of this study were to
      quantify the releases of arsenic from mulch made from C&D wood, to evaluate the
      impacts of an iron-oxide colorant in potentially decreasing arsenic leaching
      rates, and to evaluate the relative significance of additional variables on
      leachate concentrations. Atotal of 3 sets of mulch samples (0%, 5%, or 100% CCA
      treated wood) were prepared containing a sample either with or without colorant
      addition. Each sample was subjected to two tests: a field leaching test and the
      Synthetic Precipitation Leaching Procedure (SPLP). Results showed that arsenic
      concentrations in the field leachate from the 0% treated wood mulches were
      consistently low (<0.003-0.013 mg/L) whereas leachates from 5 and 100% treated
      wood mulches were characterized by higher arsenic concentrations (0.059-2.23 mg/L
      for 5%; 0.711-22.7 mg/L for 100%). The mass of arsenic leached from the field
      samples during the 1-year monitoring period was between 10 and 15% of the initial
      mass of arsenic. The colorant reduced the leaching of arsenic by more than 20%
      for the field leachate and 50% for the SPLP leachate, on average. However, the
      study showed that the effect may not last for long periods. Besides colorant
      addition other factors were observed to affect the amount of arsenic leached from
      contaminated mulch. These include the proportion of CCA-treated wood in the
      mulch, time, and pH of rainfall.

PMID- 16955915
TI  - Development of the method and U.S. normalization database for Life Cycle Impact
      Assessment and sustainability metrics.
AB  - Normalization is an optional step within Life Cycle Impact Assessment (LCIA) that
      may be used to assist in the interpretation of life cycle inventory data as well
      as life cycle impact assessment results. Normalization transforms the magnitude
      of LCI and LCIA results into relative contribution by substance and life cycle
      impact category. Normalization thus can significantly influence LCA-based
      decisions when tradeoffs exist. The U. S. Environmental Protection Agency (EPA)
      has developed a normalization database based on the spatial scale of the 48
      continental U.S. states, Hawaii, Alaska, the District of Columbia, and Puerto
      Rico with a one-year reference time frame. Data within the normalization database
      were compiled based on the impact methodologies and lists of stressors used in
      TRACI-the EPA's Tool for the Reduction and Assessment of Chemical and other
      environmental Impacts. The new normalization database published within this
      article may be used for LCIA case studies within the United States, and can be
      used to assist in the further development of a global normalization database. The
      underlying data analyzed for the development of this database are included to
      allow the development of normalization data consistent with other impact
      assessment methodologies as well.

PMID- 16955916
TI  - Herbicidal effects of statin pharmaceuticals in Lemna gibba.
AB  - Statin pharmaceuticals, heavily prescribed in the treatment of
      hypercholesterolemia, are competitive inhibitors of 3-hydroxy-3-methylglutaryl
      coenzyme-A reductase (HMGR). In plants, these compounds also inhibit HMGR, which
      regulates cytosolic isoprenoid biosynthesis in the mevalonic acid (MVA) pathway.
      Phytotoxicity was evaluated in the higher aquatic plant Lemna gibba exposed to
      atorvastatin and lovastatin for 7-days by measuring the concentrations of sterols
      and ubiquinone; products downstream in the MVA pathway. The efficiency of the
      parallel and unaffected methylerythritol phosphate pathway (MEP) was also
      evaluated by measuring the end product, plastoquinone. Statin treatment caused an
      accumulation of plastoquinone, and unexpectedly, ubiquinone, an artifact likely
      due to metabolite sharing from the plastidial MEP pathway. Statins were, however,
      highly phytotoxic to L. gibba and HPLC-UV analysis of plant extracts showed
      significantly decreased concentrations of both stigmasterol and beta-sitosterol,
      which are critical components of plant membranes and regulate morphogenesis and
      development. EC10 values for atorvastatin and lovastatin were as small as 26.1
      and 32.8 microg/L, respectively. However, hazard quotients indicated that statins
      present little risk to the model higher aquatic plant Lemna gibba at
      environmentally relevant concentrations, even though pathway-specific endpoints
      were 2-3 times more sensitive than traditional gross morphological endpoints
      typically used in risk assessment.

PMID- 16955917
TI  - Toxicogenomic response of Staphylococcus aureus to peracetic acid.
AB  - Staphylococcus aureus is responsible for many incidents of hospital-acquired
      infection, which causes 90,000 deaths and dollars 4.5 billion loss a year in the
      United States. Despite a wide use of disinfectants such as peracetic acid in
      health care environments, we certainly need better understanding of the effects
      of antimicrobial application on target pathogens to avert infection outbreaks.
      Consequently, herein, we explored for the first time the toxicogenomic response
      of S. aureus to a sublethal concentration of peracetic acid (1 mM) by using
      microarray-based transcriptome analysis. In particular, we investigated the
      dynamics of global gene expression profiles during its cellular response, which
      involved initial growth inhibition (10 min) and subsequent partial recovery (20
      min). Further, we compared transcriptome responses to peracetic acid between S.
      aureus and Pseudomonas aeruginosa. Our findings show that (i) the regulation of
      membrane transport genes was significantly altered, (ii) DNA repair and
      replication genes were selectively induced, and (iii) primary metabolism-related
      genes were differently repressed between the two growth states. Most
      intriguingly, we revealed that many virulence factor genes were induced upon the
      exposure, which proposes a possibilitythatthe pathogenesis of S. aureus may be
      stimulated in response to peracetic acid.

PMID- 16955918
TI  - Implications of pulsed chemical exposures for aquatic life criteria and
      wastewater permit limits.
AB  - Subacute effects of pulsed copper, zinc, or ammonia exposures were examined,
      including a range of pulse concentrations, durations, frequencies, and recovery
      times between pulses, using short-term chronic Pimephales promelas and 21-d
      Daphnia magna tests. Sublethal effects were rarely observed independent of
      mortality. Effects were observed only at concentrations near the species
      continuous exposure 48 h LC50 for each chemical. Daphnia often rebounded from
      temporary reproduction effects, meeting or exceeding control responses by the end
      of the test. Effects of 24 h ammonia or copper pulses were diminished soon after
      the pulse was removed, while 24 h zinc pulses caused continued effects for
      several days following removal of the pulse, indicating a slower uptake and/or
      depuration rate for zinc. D. magna exhibited less mortality as copper pulses were
      spaced further apart, while fish were equally or more affected with longer
      recovery times between copper pulses, indicative of different adaptation
      mechanisms between the two species. Responses were not predictable based on
      either average concentration or a combination of duration and concentration.
      Chronic water quality criteria and effluent permit limits, expressed as a 4- or
      30-d average concentration, respectively, may not be appropriate for protecting
      against effects of pulsed exposures, depending on the frequency, magnitude, and
      duration of pulses, as well as the recovery period between events.

PMID- 16955919
TI  - The occurrence of organochlorines in marine avian top predators along a
      latitudinal gradient.
AB  - The aim of this study was to determine the role of cold condensation and
      fractionation on the occurrence of organochlorine contaminants (OCs) in avian
      marine top predators along a latitudinal gradient. We measured 24 polychlorinated
      biphenyl (PCB) congeners and six pesticide OCs in blood of great black-backed
      gulls (Larus marinus) from the Norwegian Coast (58 degrees N-70 degrees N) and
      glaucous gulls (Larus hyperboreus) from Bjornoya in the Norwegian Arctic (74
      degrees N). Glaucous gulls had up to 3 times higher sigmaOC concentrations
      compared to the great black-backed gulls, and a OC pattern dominated largely by
      persistent and low volatile compounds such as highly chlorinated PCBs and
      metabolites such as oxychlordane. This was not consistent with cold condensation
      and fractionation theory, but probably related to diet and elevated
      biomagnification. Among great black-backed gulls, however, there were indications
      of both cold condensation and fractionation. Higher and lower chlorinated PCBs
      had highest absolute concentrations in the south and in the north, respectively,
      except for one location at an intermediate latitude, where concentrations of most
      OCs exceeded all other locations. In terms of proportional contribution to
      sigmaOC (pattern), relatively volatile OCs such as HCB, oxychlordane and tri- to
      penta- PCB congeners were more important at northern latitudes, while hexa- to
      nona-PCBs made up a larger proportion of sigmaOC in the south. The results thus
      showed that differences in global distribution of compounds with different
      physicochemical properties could be detected in avian top predators such as large
      gulls, even if biomagnification and biotransformation influence both the absolute
      concentrations and the patterns of OCs.

PMID- 16955920
TI  - Nonylphenol isomers differ in estrogenic activity.
AB  - Nonylphenol belongs to the most investigated xenohormones acting at the estrogen
      receptor. Technical nonylphenol contains approximately 20 para-substituted
      isomers. Because of limitations in testing and quantifying all 20 isomers in the
      mixture, the linear form, 4n-NP, is often used as a reference substance, even
      though it is not present in the technical mixture. Here, we report on the
      synthesis and estrogenic potency of six nonylphenol isomers that occur at
      different proportions in technical nonylphenol mixtures. The relative potency of
      each isomer was determined by use of the MVLN transcriptional activation cell
      assay. As well, a subset of isomers was tested in the E-screen assay. One isomer,
      p353-NP, exhibited the same relative potency as the nonylphenol mixture, whereas
      the other isomers were found to be less potent. Two isomers, p22-NP and p262 NP,
      and the linear 4n-NP were found to be weak ER agonists with responses near the
      detection limit in the MVLN assay. Two isomers, p262-NP and 4n-NP, exhibited
      measurable activity in the E-screen. Our results demonstrate that defined p-NP
      isomers are most suitable for reflecting the estrogenic potency of technical NP
      mixtures. Among other applications, they should be used in the future to explain
      differences in estrogenic potency due to NPs as detected by various in vitro
      assays.

PMID- 16955921
TI  - The interference of pharmaceuticals with endogenous and xenobiotic metabolizing
      enzymes in carp liver: an in-vitro study.
AB  - The interactions of fibrate (clofibrate, fenofibrate, bezafibrate, gemfibrozil),
      antiinflammatory (ibuprofen, diclofenac, naproxen, ketoprofen), and anti
      depressive (fluoxetine,fluvoxamine, paroxetine) drugs with CYP catalyzed pathways
      (CYP1A, CYP3A-, CYP2K-, and CYP2M-like) and Phase II activities (UDP
      glucuronosyltransferases and sulfotransferases), involved in both xenobiotic and
      endogenous metabolism in fish, were investigated in-vitro by incubating carp
      liver subcellular fractions in the presence of the substrate and the selected
      drug. Anti-depressive drugs were strong inhibitors of CYP1A (92-94% inhibition),
      CYP3A-like (69-80% inhibition), and CYP2K-like (36-69% inhibition) catalyzed
      activities, while antiinflammatory drugs were potent CYP2M-like inhibitors (32
      74% inhibition). Among the lipid regulators, gemfibrozil strongly inhibited CYP2M
      catalyzed activity (91% inhibition) and other CYP isoforms (CYP1A and CYP3A
      like). Additionally, glucuronidation of naphthol and testosterone were targeted
      by antiinflammatory drugs, and to a lesser extent, by fibrate drugs (48-78%
      inhibition). No significant alteration on sulfotransferase activities was
      observed, apart from a minor inhibitory effect of clofibrate, gemfibrozil, and
      fluoxetine on the sulfation of estradiol. Overall, gemfibrozil, diclofenac, and
      the three anti-depressive drugs appear to be the pharmaceuticals with the highest
      potential to interfere with fish metabolic systems.

PMID- 16955922
TI  - Withholding sexual history presents legal risks.

PMID- 16955923
TI  - [Bronchial asthma--changes in its concept and guideline].

PMID- 16955924
TI  - [Epidemiology of asthma (including fatal cases)].

PMID- 16955925
TI  - [Airway inflammation and remodeling in bronchial asthma].

PMID- 16955926
TI  - [Airway hypersensitivity].

PMID- 16955927
TI  - [Diagnostic approach in bronchial asthma].

PMID- 16955928
TI  - [Update in asthma therapy. Management of acute exacerbation (asthmatic attacks)].

PMID- 16955929
TI  - [Step-wise chemotherapy for asthma using drugs for a long-term therapy].

PMID- 16955930
TI  - [Update in asthma therapy. Inhalation steroids].

PMID- 16955931
TI  - [Update in asthma therapy. Long-acting beta-2 agonists].

PMID- 16955932
TI  - [Update in asthma therapy. Leukotriene receptor antagonists].

PMID- 16955933
TI  - [Update in asthma therapy. Slow-release theophylline].

PMID- 16955934
TI  - [Asthma-related diseases. Aspirin hypersensitivity].

PMID- 16955935
TI  - [Asthma-related diseases. Cough-variant asthma and similar diseases].

PMID- 16955936
TI  - [Asthma-related diseases. Churg-Strauss syndrome].

PMID- 16955937
TI  - [Analysis of asthma-related genes].

PMID- 16955938
TI  - [Bronchial asthma and QOL].

PMID- 16955939
TI  - [Bronchial asthma and gender-specific medicine].

PMID- 16955940
TI  - [Bronchial asthma: management of clinical patients. Discussion].

PMID- 16955941
TI  - [Primary Sjogren's syndrome with recurrent aseptic meningitis].

PMID- 16955942
TI  - [Fever: an atypical manifestation of gastric inflammatory fibroid polyp].

PMID- 16955943
TI  - [Simultaneous occurrence of extramedullary liver plasmacytoma and Hodgkin's
      disease].

PMID- 16955944
TI  - [Cell differentiation and regeneration of the adrenal glands].

PMID- 16955945
TI  - [Eosinophilic inflammation in bronchial asthma: its re-evaluation].

PMID- 16955946
TI  - Boning up on osteoporosis--current thinking on management. Interview by Emma
      Buchanan.

PMID- 16955947
TI  - MRSA: We can overcome, but who will lead the battle?

PMID- 16955948
TI  - Outcome of a workshop on archiving structural models of biological
      macromolecules.

PMID- 16955949
TI  - Surgical images: musculoskeletal. Elbow mass in a 58-year-old woman.

PMID- 16955950
TI  - Radiology for the surgeon. Musculoskeletal case 37.

PMID- 16955951
TI  - Surgical images: soft tissue. Recurrent deep vein thrombosis caused by hypoplasia
      of the inferior vena cava.

PMID- 16955952
TI  - Multi-million BEE deal in pharmaceutical industry.

PMID- 16955953
TI  - Cystic lymphangioma of the lesser sac.

PMID- 16955954
TI  - Race, ethnicity and medical research.

PMID- 16955955
TI  - Monitoring health research finances.

PMID- 16955956
TI  - Postprandial glucose and its role in type 2 diabetes.

PMID- 16955958
TI  - [Benign prostatic hyperplasia -- transurethral holmium-laser enucleation even in
      large prostate].

PMID- 16955957
TI  - [Superficial bladder carcinoma -- trend of less aggressive therapies].

PMID- 16955959
TI  - [Evaluation of guideline for stomach cancer mass screening].

PMID- 16955960
TI  - [Clinical registers and epidemiological surveillance in the field of dementias].

PMID- 16955961
TI  - Activated human Hageman factor (XII).
AB  - An improved method for the isolation of highly purified active human Hageman
      factor has been described. An overall recovery of 25% with a purification of
      10(6) has been achieved. Certain of the physical and chemical characteristics of
      XII have been elucidated. Selective chemical modification of functional groups
      and a variety of enzymatic assays have been employed in an effort to shed light
      on the mechanism of action of this procoagulant.

PMID- 16955962
TI  - A study of antihaemophilic globulin (factor VIII) consumption.
AB  - A study has been made of the rate of disappearance of factor VIII during the
      clotting of normal plasma samples and of samples deficient in factors V, VII, IX,
      X, XI and XII. The rate of disappearance (or consumption) of factor VIII was the
      same in the normal and factor VII deficient samples. Delayed disappearance of
      factor VIII was observed in samples deficient in factors V, IX, X, XI and XII.
      The significance of the findings to the theory of blood coagulation is discussed.

PMID- 16955963
TI  - Studies on tissue thromboplastin. II. Species specificity.
AB  - Purified brain tissue thromboplastins of human, bovine and chicken origin have
      been tested on homologous and heterologous plasmas. Purified brain tissue
      thromboplastin is species specific. Lipid extracts from purified brain tissue
      thromboplastin prepared with pyridin show a negligable residual species
      specificity, probably caused by a slight contamination with brain tissue
      thromboplastin. The activity curves of our lipid extracts differ from typical
      curves expected for lipid activators by a less distinct inhibition in high
      concentrations probably caused by a different composition of petrol-ether and
      pyridin extracts. The protein part of tissue thromboplastin does not activate
      prothrombin in any system. The protein part of tissue thromboplastin of one
      species could be combined with the lipid part of another species to form an
      active tissue thromboplastin. The species specificity of these combinations was
      determined by the source of protein used.

PMID- 16955964
TI  - A study of the cation- and pH-dependent stability of factors V and VIII in
      plasma.
AB  - The in vitro lability of factors V and VIII in plasma has been studied. In
      agreement with previous reports, an increase in anticoagulant concentration
      renders both factors more labile (cation-deficient decay), as does an increase in
      the pH above 7.3 (alkaline-decay). Calcium appears to be the plasma cation which
      protects factors V and VIII against in vitro loss of activity. The protection
      obtained by the addition of other divalent cations depended on the type of plasma
      used. When resin-EDTA plasma was made cation free by dialysis at 4 degrees C and
      then incubated at 37 degrees C, the rapid loss of factors V and VIII activity
      could be prevented by prior addition of strontium, manganese and magnesium. In
      oxalate plasma, nickel, manganese, cadmium and strontium were effective. The
      alkaline decay of both factors V and VIII is irreversible. Partial reversibility
      of the cation-deficient decay was demonstrated for factor V, but not for factor
      VIII. The temperature coefficient for both the cation-deficient and alkaline
      decay is 2-3, suggesting an enzymatic rather than a physical reaction. There was
      no evidence to implicate thrombin, plasmin or trypsin since inhibitors of these
      enzymes failed to modify either type of decay.

PMID- 16955965
TI  - The fibrinotic index and evidence for a balanced regulation of coagulation
      activities.
AB  - The fibrinogen, plasma antithrombin, and thrombin activity curves of twenty-four
      normal individuals were determined under carefully controlled conditions of
      analysis. From these determinations plasma prothrombin and thromboplastic
      activities were calculated. These activities were defined in kinetic terminology
      and a theoretical rate of fibrination in plasma was calculated and used as a
      basis for comparing plasmas. Compensatory relationships were found among the
      various activities. Thus, low values of thromboplastic activity were associated
      with increased concentrations of prothrombin and fibrinogen; the effect of the
      latter activities in increasing the potential of plasma for fibrination was
      moderated by an increase in antithrombin activity. The fibrin-forming potential
      of each plasma was calculated relative to the mean value for all plasmas, to
      furnish a fibrinotic index. The latter was relatively constant in spite of wide
      variations in discrete activities, indicating that a physiological balance is
      maintained among those coagulation factors responsible for fibrination.

PMID- 16955966
TI  - Haemophilia A in a girl with female sex-chromatin pattern.
AB  - A sporadic case of haemophilia is diagnosed in an eleven year old girl. The AHG
      level was 1-1.25%. Chromosome studies have shown female sex-chromatin pattern.

PMID- 16955967
TI  - The treatment of patients with factor-V deficiency.
AB  - Two patients with congenital factor-V deficiency and a third with a combined
      deficiency of factor V and factor VIII are described. Under cover of fresh frozen
      plasma, tooth extractions were performed on two of these patients and spontaneous
      bleeding arrested. It is concluded that the achievement of a blood level of
      factor V of 20 per cent once daily is sufficient to assure adequate haemostasis.
      A low recovery of factor V activity in the plasma following infusion was found.
      However, in spite of this, adequate blood levels were easily attained due to the
      excellent preservation of factor V activity in the stored fresh frozen plasma.

PMID- 16955968
TI  - [Effect of the activity of an indirect anticoagulant by a monoamine oxidase
      inhibitor].
AB  - The combinations of some anticoagulants (phenindione, chlorphenadione,
      diphenadione, phenprocoumon, 3-[1-(p-chlorophenyl)propyl]-4-hydroxycoumarin,
      cumachlor and acenocoumarol) with MAO-inhibitors (phenylcyclopropylamino
      hydrochloride, isocarboxazid, iproniazid, nialamide and p-chloro-N'-[2
      (isopropylcarbamoyl)-1-methylethyl]benzohydrazide) were investigated with regard
      to modification of the anticoagulant activity in the rat. The activity of some
      anticoagulants like phenindione may be enhanced by the addition of MAO
      inhibitors, whereas others (chlorphenadione, phenprocoumon) are only slightly or
      not at all influenced. The MAO-inhibitors phenylcyclopropylamino hydrochloride
      and nialamide show enhancement of activity in most combinations whereas
      iproniazid never does. The other MAO-inhibitors lie between these two extremes.

PMID- 16955969
TI  - Purification and kinetic studies on a circulating anticoagulant in a suspected
      case of lupus erythematosus.
AB  - A circulating anticoagulant in a suspected case of lupus erythematosus has been
      highly purified by a combination of Sephadex gel filtration and DEAE cellulose
      chromatography. The inhibitor is a gamma globulin with a sedimentation
      coefficient of 6.6 Svedberg units. For its anticoagulant action, the lupus
      inhibitor requires a co-factor which is present both in the lupus and normal
      blood. The cofactor is located in the gamma globulins fraction which is
      relatively heat stable, but less than the inhibitor, at 56 degrees C. The active
      lupus inhibitor (inhibitor + cofactor) is not species specific against human
      prothrombin. Working with highly purified systems, the active inhibitor is found
      to inhibit prothrombin conversion by formed prothrombin activator. It does not
      appear to inhibit the formation of prothrombin activator nor does it affect
      purified prothrombin.

PMID- 16955970
TI  - Mechanism of action and some properties of a tissue activator of plasminogen.
AB  - Improvements in preparations of tissue activator and plasminogen and termination
      of activation by epsilon aminocaproic acid have permitted the use of a
      quantitative caseinolytic assay for the measurement of the plasmin formed. The
      following data indicate that the activation of plasminogen by tissue activator is
      catalytic: a) Biphasic curve obtained when velocity was plotted against
      plasminogen concentration. b) First order kinetics. c) Dependence of the turnover
      number on tissue activator concentration. The temperature and pH stability of
      tissue activator were similar to those reported for urokinase. Since both of
      these enzymes have now been shown to activate plasminogen by a catalytic
      mechanism, these data support the suggestion that urokinase may be an excretory
      form of tissue activator which has been released into the circulation.

PMID- 16955971
TI  - Plasminogen assay by means of the lysis time method.
AB  - The lysis time method for the determination of plasminogen has been investigated
      using plasminogen-free thrombin and fibrinogen preparations. The experiments have
      shown that the lysis of a fibrin clot is the result of two consecutive reactions:
      the formation of fibrin which proceeds as a first order reaction and the
      degradation of fibrin which proceeds as a zero order reaction. Plasminogen is
      activated in a separate reaction. If the rate of the fibrin formation is much
      greater than the rate of degradation, the lysis of the fibrin clot is
      approximately of zero order in fibrin. The lysis time will then be inversely
      proportional to the plasmin concentration and proportional to the fibrinogen
      concentration. In a double logaritmic system the correlation between lysis time
      and plasmin activity is a straight line with a slope of 135 degrees. Plasminogen
      is rapidly activated with streptokinase. Maximal activation is obtained only with
      a certain streptokinase concentration. Higher concentrations inactivate plasmin
      and with lower concentrations, the maximal activity is never reached. A
      spontaneous inactivation is seen after about 30 minutes. With urokinase, a higher
      maximal plasminogen activity is obtained than with streptokinase. Urokinase in
      higher concentrations does not inactivate plasmin. A standard assay for
      determination of plasminogen by the lysis time method has been worked out and is
      based on these results.

PMID- 16955972
TI  - A comparative study of the inhibitors of fibrinolysis in human, dog and rabbit
      blood.
AB  - Comparison of sera from dog, rabbit and man shows that dog serum contains most
      fibrinolytic inhibitor and human serum least. The inhibitors are potentiated by a
      variety of inorganic salts, of which sodium chloride is most effective.
      Euglobulin fractions precipitated from rabbit and human plasma at pH 5.3 contain
      small amounts of inhibitory material, whereas little remains in the corresponding
      dog euglobulin or in euglobulins from all three species when precipitated at pH
      6.0. The potentiation of fibrinolytic inhibitors by sodium chloride differs
      between the three species, suggesting that their composition is not identical.
      Chloroform extraction removes a proportion of the inhibitory material from each
      serum.

PMID- 16955973
TI  - A comparison of the esterase (TAMe) and clotting activities of human and bovine
      thrombin preparations.
AB  - A comparison has been made between the clotting activity (C) and TAMe esterase
      activity (E) during prothrombin activation and subsequent purification of human
      thrombin. A limited number of studies were made using bovine thrombin for
      comparison purposes. Under certain circumstances, the ratio of C to E for human
      thrombin is not constant, particularly upon gel-filtration at low ionic strength
      and during prolonged contact with 25% sodium citrate. Under other circumstances,
      however, these enzymic parameters are stable and human thrombin appears to have a
      ratio of C to E of approximately 6 while bovine thrombin has a ratio of 3. This
      finding may confirm the observations of others concerning the higher specific
      activity of human thrombin than the bovine enzyme against bovine fibrinogen. Only
      a single component having C and E activity has been isolated from human
      prothrombin preparations activated to thrombin by sodium citrate or biologically
      and purified by either gel filtration or ion exchange chromatography. Kinetic
      studies on human thrombin preparations indicate that in all other respects they
      are similar in enzymic properties to those reported for the purified bovine
      enzyme.

PMID- 16955974
TI  - Studies on autoprothrombin C thrombin relationship.
AB  - In every prothrombin activation two different enzymatic reactions can be
      distinguished. The first reaction is the prothrombin disappearance and the second
      one is the thrombin formation. Autoprothrombin C catalyzes both reactions and
      thrombin only the first one. The inhibition of thrombin with heparin allows a
      more complete activation of the thrombin. The two reactions can be independently
      catalyzed by different substances. Heparin by itself can provide the environment
      for activation.

PMID- 16955976
TI  - Platelet aggregation in Waldenstrom's macroglobulinaemia.
AB  - The morphology of coagula obtained in the cone in cone viscometer is studied in
      two cases of Waldenstrom's macroglobulinaemia. Whereas the structures obtained in
      normal individuals have the features of in vivo thrombosis, the platelet masses
      usually obtained are not present in the two patients studied. t is postulated
      that disturbance of platelet aggregation as demonstrated may account for the
      bleeding diathesis in some cases of Waldenstrom's macroglobulinaemia.

PMID- 16955975
TI  - An experimental obliterating thromboangiitis limited to the posterior part of the
      body.
AB  - After a brief outline of the principles involved in the production of
      thrombohemorrhagic phenomena (THP) with special organotropic localizations, an
      experimental technique is described which permits the production of acrocyanosis
      and thrombohemorrhagic lesions largely limited to the posterior part of the body.
      This phenomenon can be consistently produced by certain combinations of THP
      elicitors, anaphylactoid agents and noradrenaline (NA). The most effective
      combination among those tested is thorium dextrin (Th-Din) plus tannic acid plus
      NA. Several drugs can decisively influence the course of this reaction. Most
      otable among these are Neo-Antergan (an antihistaminic) which sensitizes for the
      production of the aboral THP, while heparin (presumably through its anticoagulant
      effect) and Dibenamine (presumably through its antiadrenergic action) offer
      virtually complete protection. When only Th-Din plus tannic acid is given, there
      develops an intense but reversible cyanosis in the hind paws and tail; additional
      treatment with NA induces obliterating thromboangiitis with hemorrhages and
      gangrene. None of hese changes are produced by Th-Din, tannic acid or NA alone.
      Evidently, here, e are dealing with pluricausal experimental diseases whose
      possible relationship to Raynaud's disease, thromboangiitis obliterans and
      anaphylactoid purpura is briefly discussed.

PMID- 16955977
TI  - [Elevated platelet count-compensated thrombasthenia in a patient with Pelger's
      disease].
AB  - Thrombocytosis and thrombasthenia have been observed in a patient with Pelger's
      nuclear anomaly of the leukocytes. It was demonstrated with the platelet
      equivalent value and the retraction expressed in percent of the norm that the
      increased platelet count compensates the thrombasthenia. The retraction in the
      total system is therefore in the normal range.

PMID- 16955978
TI  - Basic enzymology of blood coagulation.

PMID- 16955979
TI  - Hemostasis as a total physiological function.
AB  - The hemostasis is due to the combined action of several systems, blood
      composition, blood flow and vessels. The author reviews the factors which
      determine the vessel integrity and promote the repair after trauma.

PMID- 16955980
TI  - [Owner, authors and readers of the Journal of Psychiatry].

PMID- 16955981
TI  - [The relationship between traumatic experiences and dissociative phenomena].
AB  - BACKGROUND: Intuitively we are convinced that there must be a causal relationship
      between traumatic experiences and dissociation. However, although the theory is
      both elegant and attractive, the existence of a direct causal link between trauma
      and dissociation is open to question. Available studies on this theme have
      methodological shortcomings. AIM: To obtain more insight into the frequency with
      which psychiatric patients have undergone traumatic experiences and to find out
      more about the relationship between theses experiences and dissociative
      phenomena. METHOD: Over a period of two years new outpatients attending
      psychiatric clinics completed questionnaires about their past life and mental
      health; in these questionnaires they gave information about traumatic
      experiences, dissociative phenomena, psychological symptoms and psychological
      functioning. RESULTS: Only 38 of the 351 patients who completed the questionnaire
      stated that they had never had any traumatic experiences. A relatively large
      number of patients mentioned that they had experienced emotional deprivation in
      their family of origin. The correlation coefficient between traumatic experiences
      and the scores for dissociative phenomena was 0.30. CONCLUSION: In view of the
      weak positive correlation between traumatic experiences and dissociative
      phenomena the hypothesis of a linear causal relationship seems unlikely. It is
      possible that the relationship is based partly on the poorer general
      psychological functioning that follows exposure to traumatic experiences.

PMID- 16955982
TI  - [Pharmacotherapy for Alzheimer's disease].
AB  - BACKGROUND: So far no causal therapies are available for the treatment of
      Alzheimer's disease. However, four drugs, namely donepezil, rivastigmine,
      galantamine and memantine, have been licensed for treating the symptoms of the
      disease. AIM: To systematically review the efficacy and side-effects of these
      drugs. METHOD: With the help of Pubmed, Medline and the Cochrane Library the
      literature was searched systematically. RESULTS: Cholinesterase-inhibitors and
      memantine do have a beneficial effect on cognition and daily functioning. The
      effect, however, is limited and the cholinesterase-inhibitors in particular
      frequently have side-effects. CONCLUSION: Treatment with the new anti-Alzheimer
      drugs demands a careful and realistic approach. The drugs should not be
      prescribed in isolation but the treatment needs to be embedded in the entire set
      of currently available psychosocial intervention techniques.

PMID- 16955983
TI  - [Dismantling of the mental healthcare sector. Developments, trends and
      controversies in the Netherlands].
AB  - BACKGROUND: The advisory document 'Zorg voor Velen '(Care of Many) (2002) calls
      for the dismantling of the large integrated mental healthcare institutions in the
      Netherlands. The minister of Health has taken the advice contained in that
      document, thus bringing to an end a period of thirty years when policy was
      directed towards more cohesion in the mental healthcare services. The reactions
      to this change in policy vary tremendously. AIM: To describe developments within
      the mental healthcare system and to interpret the advice that was offered and the
      reactions to it. METHOD: A historical analysis of the Dutch mental healthcare
      service since 1970 and an interpretation of the indicators and policy choices.
      RESULTS: The Dutch mental healthcare service has developed into one large
      healthcare sector and as a result many institutions have been forced to merge. At
      the same time the number of patients in this sector has increased dramatically,
      whereas the number of psychiatric patients in primary care has decreased.
      Meanwhile, care has moved in the directions of medically specialised care, partly
      because tasks and responsibilities have been transferred from one discipline to
      another. CONCLUSIONS: The movement towards one large single integrated care
      sector has led to the categorisation of care for the mentally ill and has
      increased the number of patients in the mental healthcare sector. Treatment has
      become more medicalised and specialised. As a result the mental healthcare system
      has found itself in an intolerable situation. The situation can only be resolved
      if a much sharper distinction is made between general primary care and
      specialised secondary care and ifsteps are taken to forge links with general
      health care.

PMID- 16955984
TI  - [Their care is our care. Comment on Hurschmaekers and Tiemens].

PMID- 16955985
TI  - [Which antipsychotic as first choice in schizophrenia? The Dutch
      Multidisciplinary Guideline for Schizophrenia 2005 versus the Pharmacotherapy
      Compass 2005, the Dutch National Health Insurance System Formulary].
AB  - The pharmacotherapy advice contained in the 'Multidisciplinaire Richtlijn
      Schizofrenie 2005' (abbreviated to MDRS 2005 and translated as the Dutch
      Multidisciplinary Schizophrenia Guideline) is compared with the advice given in
      the 'Farmacotherapeutisch Kompas 2005' (abbreviated to FTK 2005 and translated as
      the Pharmacotherapy Compass 2005) and with international guidelines. FTK 2005,
      which is the Dutch National Health Insurance Formularium, recommends that
      treatment should start with a conventional (first-generation) antipsychotic,
      namely haloperidol. International guidelines, however, advise starting with an
      atypical (second-generation) antipsychotic. MDRS 2005 suggests that the pros and
      cons of the medication should be discussed with the patient and that the choice
      of drug should be based on the outcome of this discussion. Ifthat discussion
      becomes problematical then, according to MD RS 2005, it is advisable

PMID- 16955986
TI  - ['Evidence-based medicine' in the Dutch and Flemish psychiatric, psychological
      and psychotherapeutic specialist literature: widely used?].
AB  - The expression 'evidence-based medicine' was first used in medical journals in
      the 1990's. Recent research has shown that the expression appears very frequently
      in international medical publications. Until recently, however, there were no
      research data concerning the frequency with which the expression is used in the
      titles and summaries in Dutch and Flemish specialist journals in the field of
      psychiatry, psychology and psychotherapy. In our systematic review of the Dutch
      and Flemish specialist medical literature published between 1990 and 2003 we
      found that the use of the expression increased markedly as from 1997.

PMID- 16955987
TI  - [Analytic inpatient treatment of malignant narcissism. A case study].
AB  - It is extremely doubtful whether a patient diagnosed with malignant narcissism
      will respond positively to analytic therapy, particularly group therapy. The
      prospects for recovery are not favourable because a patient with malignant
      narcissism has a tendency to destroy everything that is good, including the
      therapeutic relationship, and this destructiveness can seriously undermine the
      treatment of other patients. Nevertheless, in this article a case is presented
      that illustrates that long-term analytic in-patient treatment can be successful.
      The theoretical background to the diagnosis is outlined so that readers will be
      able to understand the nature of the treatment.

PMID- 16955988
TI  - [A 'psychogenic psychosis' turns out to be a subarachnoid haemorrhage. A case
      study].
AB  - A 50-year-old woman is admitted to the emergency ward by reason of her psychotic
      state. Because she has a history of psychiatric problems and has been previously
      diagnosed as having borderline personality disorder it is assumed that she has
      had a brief psychogenic psychosis. When the psychosis recurs and the symptoms
      increase in intensity the patient is given a computerized tomography brain scan.
      The scan reveals a subarachnoid haemorrhage. In discussing this case history we
      try to interpret the symptoms of this neurological disorder against the
      background of the premorbid psychiatric diagnosis. We supplement our
      interpretation with data from case histories reported in the literature.

PMID- 16955989
TI  - Monophasic action potentials in the heart--experimental and clinical aspects.

PMID- 16955990
TI  - [Philosophy and evidence-based medicine].

PMID- 16955991
TI  - [Comparison of the effectiveness of two treatment strategies in inpatients with a
      depressive disorder. A double-blind study of imipramine followed by lithium
      addition versus fluvoxamine followed by lithium addition].
AB  - BACKGROUND: There is still uncertainty regarding the best treatment optionfor
      depressed inpatients and the best strategy to follow if patient response is
      insufficient. AIM: To compare the efficacy of imipramine and fluvoxamine in
      depressed inpatients who subsequently received lithium supplement in case of poor
      response. METHOD: After a drug-free period and four days of placebo use, patients
      were randomised either to imipramine or to fluvoxamine (phase 1); the
      antidepressant dosage was fixed according to a predetermined plasma level. The
      efficacy of the antidepressant was evaluated four weeks after the predetermined
      plasma level had been attained. If patient response was inadequate, the
      antidepressant was augmented with lithium (phase 2). Patient response to the
      lithium addition was evaluated three weeks after an adequate lithium level had
      been attained. RESULTS: The study involved 138 inpatients. At the end of phase 1,
      imipramine was found to be superior tofluvoxamine according to the Clinical
      Global Impression of Improvement. Remission was achieved by 6 (23%) patients on
      imipramine and by 10 (15%) patients on fluvoxamine; this difference was not
      statistically significant. At the end of phase 2, 41 (9%) patients on imipramine
      and 27 (40%) patients on fluvoxamine achieved remission, this significant
      difference demonstrating the superiority of the imipramine strategy. CONCLUSION:
      Imipramine with subsequent lithium addition is superior to a similar strategy
      with fluvoxamine.

PMID- 16955992
TI  - [The effectiveness of mental health care in developing countries. Intervention
      and policy options at several levels].
AB  - BACKGROUND: In developing countries psychiatric disorders are a major cause of
      disability and reduced economic productivity. AIM: To present an overview of
      intervention and policy options in mental health care in developing countries.
      METHOD: We searched the literature using PubMed, supplementing our finding with
      what we have learned from experience in the field. RESULTS: Research data, though
      very limited, indicate that psychiatric disorders can be treated effectively in
      developing countries. Mental health care can be provided at three different
      levels: at the level of the existing health care system, at primary care level
      and at community level. We discuss interventions at each of these levels on the
      basis of three cases. CONCLUSION: More research is needed into the efficacy and
      cost-effectiveness of mental health care interventions in developing countries;
      research must be accompanied by the actual implementation of mental health
      programmes in these countries.

PMID- 16955993
TI  - [Clozapine-induced agranulocytosis: genetic risk factors and an immunologic
      explanatory model].
AB  - BACKGROUND: Clozapine, an atypical antipsychotic used in the treatment of
      refractory schizophrenia, causes agranulocytosis in 0.8% of patients. The risk
      factors for clozapine-induced agranulocytosis (CIA) and the underlying mechanisms
      are unclear. AIM: To ascertain the genetic and immunological risk factors for
      CIA, and on the basis of these findings to construct an explanatory model for
      CIA. METHOD: We reviewed the literature via Medline (from 1966 to May 2004) and
      EMBASE (from 1980 to May 2004) using the search terms 'clozapine' and
      'agranulocytosis'. RESULTS: We found 8 case-control studies that fulfilled our
      selection criteria. In schizophrenia patients, CIA appeared to be significantly
      associated with certain haplotypes of HLA (human leukocyte antigens) genes, with
      the 4b,3d microsatellite alleles of TNF (tumor necrosis factor), with variant
      genes of HSP 70 (heat-shock protein), and with NQO2 (dihydronicotinamide riboside
      quinone oxidoreductase) gene polymorphism. Most of these genetic findings are
      interrelated. Gene abnormalities of this kind probably play an important
      aetiological role in CIA and may provide a basis for the construction of an
      immuno-toxic explanatory model for CIA. CONCLUSION: It seems likely that CIA can
      be explained on the basis of genetic and immunotoxic factors. The model should
      help us to understand how agranulocytosis can be caused by various antipsychotics
      and how it can be treated. However, it is not yet possible to identify patients
      who are particularly at risk for CIA.

PMID- 16955994
TI  - [ADHD, a 'fashion' that won't go out of fashion. An illustration of the many
      sidedness of earlier psychiatry].
AB  - BACKGROUND: This article reviews the older Dutch literature on what is now known
      as ADHD (attention deficit hyperactivity disorder). METHOD: Because this older
      literature is not included in electronic databases, it was traced, in a
      systematic and a selective manner, by means of bibliographic references. RESULTS:
      It is often assumed that ADHD is a purely Anglo-Saxon phenomenon that was
      introduced into The Netherlands along with the concept of MBD (minimal brain
      damage). This assumption is incorrect. In fact, ADHD has had quite a long,
      respectable history of its own in The Netherlands (and in surrounding countries).
      The antecedents of ADHD were regarded as very common phenomena. Over the years
      these concepts have often been the subject of considerable controversy.
      Biological factors were thought to be important in the etiology. CONCLUSION: It
      would be wrong to regard ADHD only as a fashionable ailment originating in the
      age of computers and working mothers. Equally untenable is the current view that
      pre-DSM III child psychiatrists attributed psychiatric disorders solely to
      parental influences ('parent-blaming'). The same conclusion was drawn in other
      publications by the author. The history of ADHD thus demonstrates that, contrary
      to general belief, early psychiatry in The Netherlands was more balanced and many
      sided.

PMID- 16955995
TI  - [Is there a big role for the little brain in psychiatry?].
AB  - The cerebellum is a structure situated in the posterior cranial fossa. It has
      long been assumed that the cerebellum is concerned primarily with motor-related
      functions. However recent research has demonstrated that the cerebellum also
      plays a role in psychiatric disorders, including schizophrenia, autism and
      depression. Recent developments, described in this article, suggest that
      malfunctioning of the cerebellum can lead to severe emotion dysregulation and to
      psychopathological conditions.

PMID- 16955997
TI  - [Acute psychiatric symptomatology in Wegener's granulomatosis].
AB  - A 69-year-old man presented with a manic episode but in fact was found to be
      suffering from Wegener's granulomatosis, a systemic disease that can attack the
      central nervous system. This case study demonstrates that in rare cases acute
      psychiatric symptoms can develop in a patient suffering from Wegener's
      granulomatosis, that need to be treated in the proper way. The purpose of the
      discussion is twofold: to draw attention to the rarity of the case and to stress
      the need for a multidisciplinary approach to systematic diseases.

PMID- 16955996
TI  - [Balint's syndrome: seeing blind].
AB  - Balint's syndrome consists of simultanagnosia, ocular apraxia and optical ataxia.
      Although various disorders may underlie this syndrome, the most frequent is
      Alzheimer's disease in its early stages. Because so few people are familiar with
      this syndrome the first reaction is often to attribute it to underlying problems
      that are primarily of a psychological nature. As a result treatment and support
      may be inadequate or given too late. The case study reported here concerns a
      female patient with Balint's syndrome. The case is supported by comparable
      symptoms found in three other patients.

PMID- 16955998
TI  - [Glucose abnormalities in a 14-year old patient treated with a second generation
      antipsychotic].
AB  - The increased risk of diabetes mellitus in adult patients treated with second
      generation antipsychotics is a topic that has been vigorously debated in recent
      years. However, a literature search indicates that only very limited information
      is available about the use and the potential metabolic risks of antipsychotics in
      children and adolescents. We present and discuss a case study in which severe
      glucose abnormalities were detected in a 14-year-old, non-psychotic patient who
      was being treated with risperidone. The glucose abnormalities were found to be
      reversible when risperidone was discontinued. The case-study highlights the
      importance of screening for and detection of metabolic abnormalities in children
      and adolescents who are being treated with second generation antipsychotics. It
      is particularly important that children with additional risk factors are closely
      monitored.

PMID- 16955999
TI  - [Reaction to "Schizophrenia and migration"].

PMID- 16956000
TI  - [Reaction to "Evidence-based medicine in the Dutch language psychiatry,
      psychology and psychotherapeutic literature: remarkably present?" Remarkably
      absent].

PMID- 16956001
TI  - [Reaction to "About the comparison of public-private cooperation"].

PMID- 16956002
TI  - [A comparative study of two methods of personality assessment, the TCI and the
      NVM (Dutch shortened version of the MMPI)].
AB  - BACKGROUND: Various types of reliable instruments are available for measuring
      personality dimensions. One of these instruments is the NVM, which is a Dutch
      shortened version of the Minnesota Multiphasic Personality Inventory, but its use
      is no longer permitted. AIM: To find out whether the Temperament and Character
      Inventory (TCI) can serve as an alternative to the NVM. METHOD: A study has
      compared the NVM questionnaire to the TCI, which is a personality questionnaire
      designed from a more psychiatric perspective. The two types of questionnaire were
      completed by 91 psychiatric (out)patients. Correlation analyses were performed.
      RESULTS: Statistically significant correlations were found between the various
      scales of the NVM and the TCI. Unique combinations of the TCI scales were found
      to predict the various NVM scales. CONCLUSION: It is worth considering the TCI as
      an alternative to the NVM.

PMID- 16956003
TI  - [Survey among readers of the Tijdschrift voor Psychiatrie].
AB  - BACKGROUND: The editorial board has defined the objectives of this journal as
      follows: to provide its readers with refreshing information, to report the
      results of scientific research and to build bridges between research and everyday
      practice. AIM: To find out what readers want and whether they support the board's
      objectives, and to use this information in planning the contents of future issues
      of the journal. METHOD: All readers were invited to complete a questionnaire
      either on paper or via the website. RESULTS: Questionnaires were completed by 255
      readers (response rate 5.7%). The average rating on a 5-point Likert scale was
      3.8. Thematic issues and issues devoted to book reviews were given a high rating.
      There seems to be a demandfor evidence-based medicine, the inclusion of
      scientific results reported in other journals and practice-based articles. No
      significant differences were found between the views expressed by readers who had
      previously submitted an article for publication and those who had not, nor
      between Flemish readers and Dutch readers. The website was not visited very
      often. CONCLUSION: The Tijdschrift voor Psychiatrie is greatly appreciated by its
      readers. They are largely in agreement with the objectives formulated by the
      editorial board. Thematic issues are highly rated and many subjects are mentioned
      by the readers for future issues. The low response to the survey can affect its
      representativity. The editorial board will take readers' wishes into
      consideration when selecting material for future issues of the journal.

PMID- 16956004
TI  - [What is a delusion? A phenomenological view].
AB  - BACKGROUND: The debate about dimensional or categorised classification ofsymptoms
      has widened to include the concept of delusions, one of the key notions in
      psychiatry. Although interrater agreement concerning the delusion concept is
      considerable, it is extremely doubtful whether approval also extends to the
      construct validity. Can the delusion concepts till be described according to the
      DSM-criteria? AIM: To describe the history of the delusion concept and to present
      current views on the subject. METHOD: The literature was reviewed with the help
      ofPubMed. RESULTS: A delusion can best be described as an individual and personal
      view which cannot befalsifted and to which patientsfeel emotionally attached.
      Most people consider a delusion to be implausible because it is expressed with
      such unshakeable certainty. With regard to a a dimension such as conviction there
      seems to be a continuum that extends from normal ideas to impaired reality
      testing. CONCLUSION: If delusions are to be considered as dimensional constructs
      this will give rise to questions concerning discriminant validity. It will become
      increasingly difficult to discriminate between delusions and other types of
      belief that are associated with impaired reality-testing.

PMID- 16956005
TI  - [...with psychotic features? An investigation into the delusional nature of
      convictions in patients with non-psychotic disorders].
AB  - BACKGROUND: In certain disorders the boundaries between thoughts, obsessions,
      overvalued ideas and delusions are not always clearly delineated. AIM: To find
      out whether delusions can be distinguished from the convictions that often
      accompany anorexia nervosa, obsessive compulsive disorder (OCD), body dysmorphic
      disorder (BDD) and hypochondriasis, all of which apparently may involve impaired
      reality testing. METHOD: The literature was reviewed with the help of PubMed,
      using as key words 'delusions' in combination with 'hypochodriasis', 'anorexia
      nervosa', 'body image', 'obsessive compulsive disorder' or 'body dysmorphic
      disorder'. We also searched the Tijdschrift voor Psychiatrie and references of
      the literature we used. RESULTS: A number of disorders can probably be classified
      on a spectrum ranging from non-psychotic to psychotic. For instance, OCD,
      hypochondriasis, BDD and to a lesser degree anorexia nervosa can all be
      particularized as 'with good insight', 'with poor insight' or 'with psychotic
      features'. CONCLUSION: Current practice in DSM-IV is to classify OCD, BDD or
      hypochondriasis and a delusional disorder as separate entities; this way of
      classifying seems to be an artefact. Our findings indicate that a dimensional
      system of classifying psychotic systems is preferable to a categorised system.

PMID- 16956006
TI  - [Is there any point in detecting high risk factors prior to a first psychosis?].
AB  - BACKGROUND: If schizophrenia and related disorders are diagnosed and treated
      early, symptoms will be less severe and the prognosis will be more favourable.
      There is little point in screening for schizophrenia in the general population
      because the illness has such a low incidence. However, we do need to find out
      whether it is meaningful to screen genetically impaired individuals (high risk
      group) and specific groups of psychiatric patients (ultra high risk group). AIM:
      To survey the research into the (high and ultra high) risk factors for developing
      a first psychosis and to find out whether it makes good sense to screen certain
      groups of persons. METHOD: We conducted extensive desk-research and a wide
      ranging search of the literature from 1990 to 2004. The key words we used in our
      search were 'prodrome', 'high risk', 'ultra high risk', in conjunction with
      'psychosis' and 'schizophrenia'. RESULTS: In the genetically impaired group risk
      factors for developing schizophrenia seem to be transient psychiatric problems in
      childhood, schizotypical traits, anxiety, behavioural problems in adolescence,
      being brought up in an unstable environment and producing deviant results in
      neurocognitive tests. Among the patients referred to a psychiatrist it is
      possible to identify a special group of patients with an ultra high risk of
      developing a psychosis. Within ayear 40% of patients who had mild or short-term
      psychotic symptoms or who were genetically impaired adolescents with decreased
      functioning had developed a psychosis. CONCLUSION: Screening all genetically
      vulnerable persons in the general population has no consequencesfor treatment.
      Early diagnosis by psychiatrists is certainly advisable. However, larger groups
      and longer studies are needed in order to demonstrate conclusively the preventive
      effect of interventions prior to a first psychosis.

PMID- 16956007
TI  - [Aggressive incidents while on crisis duty].
AB  - Being on duty in a crisis team of the Mental Health Service can be a highly
      emotional and stressful experience. Pressed for time and providing a 24-hour
      service, team-members often have to make major decisions without consulting and
      agreement of all the parties concerned. The East Brabant Mental Health Service
      (GGZ OostBrabant) felt they needed to find out more about the threatening
      behaviour encountered by the crisis team and to identify the risk factors. For
      this purpose a weekly record was kept of all the incidents that occurred and
      these were discussed and analysed with the help of the Staff Observation
      Aggression Scale-Revised. In 2002 14% of the crisis contacts involved aggression.
      A striking feature of these incidents was that they occurred relatively often at
      certain times: at the end of the morning or very late at night/in the early hours
      of morning. The weekly meeting at which the incidents can be fully discussed is
      an opportunity to pass on to all staff members the knowledge and skills needed to
      deal with aggression.

PMID- 16956008
TI  - [Breast cancer in the family: a possible contra-indication to the use of dopamine
      antagonists. A case study].
AB  - A 23-year-old woman with a family history of breast cancer suffers from a
      psychotic disorder and has symptoms of anxiety and depression. There are some
      indications in the literature that the use of dopamine antagonists can lightly
      increase the risk of developing breast cancer. So far there is insufficient
      scientific evidence to justify alterations in the standard treatment strategy
      simply on the grounds that a woman has a family history of breast cancer. We do
      however recommend that women in this risk category be tested periodically for
      possible breast cancer.

PMID- 16956009
TI  - [Topiramate for the treatment of post traumatic stress disorder. A case study].
AB  - Two patients with posttraumatic stress disorder (PTSD) were treated successfully
      with the anti-epileptic drug topiramate. Nightmares and the re-experiencing of
      traumatic events were particularly responsive to the treatment. Topiramate acted
      rapidly at a relatively low dosage and seems to be an important addition to the
      limited range of drugs availablefor treating severe symptoms of PTSD.

PMID- 16956012
TI  - [Reaction to "Dismantling of the mental healthcare sector. Developments, trends
      and controversies in the Netherlands"].

PMID- 16956013
TI  - [Reaction to 'Bitter and gilded pills: psychiatry in the light (or shadow) of the
      pharmaceutical industry' and to 'The importance of public-private cooperation.
      Comment on Vandereycken'].

PMID- 16956014
TI  - [Reaction to 'Development of psychopathology'].

PMID- 16956015
TI  - Practice update.

PMID- 16956018
TI  - [Amyloidosis].

PMID- 16956019
TI  - [Exercise-induced asthma (EIA) Synonym; Exercise-induced bronchoconstriction
      (EIB)].

PMID- 16956020
TI  - [Non-alcoholic liver disease (NASH)].
AB  - NASH, an increasingly recognized condition resembles alcohol-induced liver
      disease, but occurs in patients who do not abuse alcohol. Obesity, insulin
      resistance and oxidative stress have critical roles in the pathogenesis of NASH.
      Liver biopsy remains the only modality that can reliably distinguish steatosis
      from steatohepatitis. Simple steatosis may have the best prognosis. In patients
      with NASH liver enzymes are insensitive and can not be used reliably to confirm
      the diagnosis or stage the extent of fibrosis. Currently no effective medical
      therapy is available. Weight reduction may improve the disease. Liver
      transplantation in end-stage liver disease is a potential therapeutic option also
      in patients with NASH.

PMID- 16956021
TI  - [Chronic liver disease--diagnostic work-up].
AB  - The diagnostic work-up of patients with liver diseases includes taking a past
      history, a physical examination, incl. an abdominal ultrasound examination or a
      duplex ultrasonography, general laboratory analyses, etiology-defining analyses,
      imaging studies and in special situations a percutaneous or transjugular liver
      biopsy or a laparoscopy. Following this algorithm it is possible to identify in
      most cases the etiology of the liver disease. The exact diagnosis is key for the
      understanding of the natural course and prognosis of the liver disease and for
      the indication for therapy, the choice of the optimal therapeutic strategy and
      the assessment of its response. Of particular importance is at the time of the
      first diagnosis of a liver disease to exclude or identify coexisting etiologies,
      e. g., alcohol use and HCV infection.

PMID- 16956022
TI  - [Risk-classification in liver cirrhosis].
AB  - Prognostic models are useful in estimating disease severity and survivial and are
      used to make decisions regarding specific medical interventions. These models are
      developed using analytical methods that involve determining the effects of
      variables of interest (eg, laboratory values) on specific outcomes such as death.
      There are two models that are used commonly in the care of patients witch chronic
      liver disease: the Child-Pugh score and the recently described Model for End
      Stage Liver Disease (MELD). MELD score is a prospectively developed and validated
      chronic liver disease severity scoring system that uses a patient's laboratory
      values for serum bilirubin, serum creatinine, and the international normalized
      ratio for prothrombin time (INR) to predict survival. The score was proposed as a
      the most promising alternative to Child-Pugh score. Weather Child-Pugh score
      should definitely be abandoned for MELD score remains uncertain. The aims of this
      paper are to summarize and to compare the characteristics, applications and
      limitations of Child-Pugh and MELD scores.

PMID- 16956023
TI  - [Diagnosis because of weight loss, anorexia, nausea and epigastric pain].

PMID- 16956025
TI  - [Development of psychopathology].

PMID- 16956024
TI  - [Talc granulomatosis in poly-toxicomania with i.v. drug abuse].

PMID- 16956026
TI  - [Resident psychiatrists in Amsterdam recognize the value of personal therapy].
AB  - BACKGROUND: Resident psychiatrists in the Netherlands, unlike their counterparts
      in other countries, are obliged to undergo 50 hours of personal psychotherapy. In
      1994 Trijsburg et al. published the results of a questionnaire that had been
      completed by psychiatrists, psychologists and other persons training to become
      psychotherapists. AIM: To fnd out how resident psychiatrists in Amsterdam in 2003
      characterised and rated the therapy module in their course. METHOD: Resident
      psychiatrists in Amsterdam were asked to complete a shortened version of the 1994
      questionnaire. The Utrecht Burn-out Scale was added. RESULTS: Personal therapy
      was greatly appreciated, but the psychotherapists were more convinced of the
      positive effects than were the residents. Hardly anyone referred to any negative
      aspects. The residents did not consider personal therapy to be an essential
      element in their course. Two-thirds of the residents in Amsterdam were female, a
      large increase compared to the male-female ratio in 1994. The workload of the
      residents was in accordance with that of other workers in the health care sector.
      CONCLUSION: Since resident psychiatrists in Amsterdam have a positive attitude to
      compulsory personal therapy, there seems to be no compelling reasonfor abolishing
      this module--even though the beneficial effects of this therapy have never been
      demonstrated.

PMID- 16956027
TI  - [Hopelessness in patients with schizophrenia. Suffering from and with
      schizophrenia].
AB  - BACKGROUND: Clinical experience shows that feelings of hopelessness quite often
      arise in patients with schizophrenia. AIM: To describe these feelings of
      hopelessness, obtain insight into interrelated factors, distinguish hopelessness
      from depression, study the influence of hopelessness on suicidal behaviour
      andfind out how feelings of hopelessness can influence the treatment that is
      provided. METHOD: We searched the literature via MEDLINE and PsyCINFO using the
      key words 'schizophrenia', 'hopelessness', 'demoralization', and
      'disappointment'. RESULTS: Demoralization is a broader term than hopelessness and
      is used quite often. Positive correlations arefound between hopelessness and: (1)
      awareness of illness; (2) engulfment; and (3) depressive symptoms. Negative
      correlations are found between hopelessness and: (1) cognitive disorders; and (2)
      an avoidant coping style. Hopelessness and demoralisation cannot be equalled with
      depression. Hopelessness clearly heightens suicidal tendencies. Feelings of
      hopelessness in a patient suffering from schizophrenia signal that closer
      attention should be given to that patient. CONCLUSION: Feelings of hopelessness
      in patients with schizophrenia are not necessarily a sign of pathology but may
      point to existential suffering. This needs to be recognised by those dealing with
      persons sufferingfrom schizophrenia,

PMID- 16956028
TI  - [Psychiatrist, patient and religion: more than simply coping].
AB  - Qualitative information derived from interviews with psychiatrists working in a
      Dutch psychiatric institution shows that religion plays a role in the
      relationship between psychiatrist and patient. Religion functions not only as a
      coping mechanism, it also lies at the basis of the psychiatrist's attitude.
      Although less than 20% of the psychiatrists interviewed claimed to be religious,
      more than 75% said that the therapeutic relationship was partly founded on
      religious ideas and principles.

PMID- 16956029
TI  - [Psychiatrist and religion: unknowing or doubtful?].

PMID- 16956030
TI  - [The psychiatrist working in a multidisciplinary team and the "Revised Profile of
      the Psychiatrist." Legal and organizational statements outside reality?].
AB  - The document entitled 'Herziene Profielsschets Psychiater (Revised Profile of a
      Psychiatrist)' contains the following statement: 'Belonging to and working in a
      multidisciplinary team does not invalidate one of thefundamental rules of
      psychiatric practice according to which the psychiatrist can only refer a
      patientfor investigation and treatment if he himself has actually seen the
      patient'. This statement overlooks thefact that many psychiatrists are employees
      i.e. they work in hospitals or group practices, and are not in private practice.
      As employees they fall under a larger body of legal and organisational rules and
      regulations than do psychiatrists in private practice. The revised profile fails
      to take this aspect into account.

PMID- 16956031
TI  - [Management and guardianship as measures to prevent social breakdown in
      psychiatric patients. A case study].
AB  - Three psychiatric patients are dangerously close to social breakdown as a result
      of financial problems. They are incapable of improving their living conditions
      because they lack insight and have only very limited problem-solving ability.
      Measures such as legal guardianship or legal restraint empower someone to make
      decisions on behalf of the patient and keep the patient from social breakdown.
      The measures are additional to other forms of coercion that can be used in the
      treatment of patients with severe psychiatric disorders and social problems.

PMID- 16956032
TI  - [A cocaine-induced variant of the neuroleptic malignant syndrome. A case study].
AB  - In this article we discuss the case of a patient with schizophrenia who presented
      with the clinical symptoms ofcoma, fever and rigidity. Initially it was suspected
      that the patient had a neuroleptic malignant syndrome. Closer inspection revealed
      that the patient had recently used cocaine. It is known that cocaine can cause a
      variant of the neuroleptic malignant syndrome. The patient was treated with
      dantrolene sodium and bromocriptine in the Intensive Care Unit and made a
      complete recovery within four days.

PMID- 16956033
TI  - [Unipolar depression suddenly switches to hypomania in a patient who has just
      started taking venlafaxine].
AB  - A woman with a recurrent episode of a depression that hitherto had been unipolar
      developed a hypomania the day after her treatment with paroxetine 20 mg/day was
      switched to venlafaxine 75 mg/day. The hypomanic symptoms subsided gradually as
      the dosage was reduced and the patient thereafter remained in a euthymic state
      while on venlafaxine at a dose of 18.75 mg/day. Three possible explanations are
      discussed for the patient's response: there was a pharmacokinetic interaction
      between paroxetine and venlafaxine, the patient had an idiosyncratic reaction to
      venlafaxine or venlafaxine inhibited the re-uptake of norepinephrin.

PMID- 16956034
TI  - [Reaction to 'Psychiatric past history and health care after compulsory
      admission'].

PMID- 16956035
TI  - [Intrapartal fetal monitoring, sensitivity and specificity of methods].
AB  - OBJECTIVE: To evaluated sensitivity and specificity of presently used methods for
      intrapartal monitoring (CTG, FpO2 a STAN S-21) and their mutual comparison. TYPE
      OF STUDY: A prospective study. SETTING: Gynecological-Obstetrical Clinic, 1st
      Medical Faculty, Charles University and general Teaching Hospital, Prague.
      METHOD: In 114 pregnant women with high-risk or pathological course of pregnancy
      the authors evaluated the capability of individual methods to predict intrapartal
      hypoxia, determined on the basis of postnatal evaluation of parameters observed
      (Apgar score in 1st minute, pH from umbilical artery, lactate levels in fetal
      blood, base excess (BE) and postpartum condition of fetus evaluated by a
      neonatologist). Each method was categorized according to its importance. The
      quality of individual methods was evaluated by means of their sensitivity and
      specificity as well as by the area under ROC (Receiver Operating Characteristic),
      i.e. AUC (Area under Curve). A similar or different prediction of the condition
      of the newborn by these individual methods was evaluated by the McNamara test of
      symmetry. In 50 deliveries performed by Cesarean section and 24 forceps
      deliveries the authors evaluated postnatal pH from umbilical artery and
      evaluation by Chi-square test. The women in childbed were infused with a
      tocolytic drug (hexoprenalin) before Cesarean section. All tests were performed
      at 5% level of significance. RESULTS: Low level of Apgar score in the 1st minute
      and less) always indicated CTG, but also a large proportion of normal newborns.
      STAN, in contrast, well indicates all newborns with a normal point evaluation.
      The best balanced evaluation of the newborns is provided by FpO2 and there was a
      significant difference between CTG and FpO2. In evaluating pH from the umbilical
      artery (pH < 7.20), TCG proved to be most sensitive again but displayed low
      specificity. STAN was the best predictor of newborns with normal pH. In
      evaluating high levels of lactate (> 3.7mmol/L) and BE (> -10) and related
      demonstration of metabolic acidosis STAN proved to be the best predictor. The
      condition of the newborn evaluated by a neonatologist immediately after birth
      (medium or heavy depression) was best predicted by FpO2. In deliveries performed
      by Cesarean section and after the administration of tocolysis the postnatal pH
      was higher then in forceps deliveries without acute tocolysis. The occurrence of
      emergencies in the course of a pathological delivery in individual methods is as
      follows: CTG, FpO2 and STAN. CONCLUSION: Even though CTG displays a very low
      specificity, this method should not be rejected, since it draws attention of the
      obstetrician very early to the possibility of developing hypoxia. FpO2 or STAN
      gives more precision to the situation and demarcates a correct moment for ending
      the delivery for the indication of fetus hypoxia intra partum. STAN is the best
      predictor for conditions of developing metabolic acidosis, evaluated postnatally
      by the level of lactate and BE in fetal blood.

PMID- 16956036
TI  - [Role of ST-analysis of fetal ECG in intrapartal fetus monitoring with presumed
      growth retardation].
AB  - OBJECTIVE: Evaluation of the role of ST analysis of fetus ECG for early detection
      of developing acute hypoxia in the course of delivery of fetuses with presumed
      growth retardation. A comparison with present way of intrapartal fetus
      monitoring. Impact on the number of surgical births for indications of
      threatening fetus hypoxia. Influence of the method on perinatal results and
      postnatal adaptation of the newborns. TYPE OF STUDY: A prospective study.
      SETTING: Gynecology-Obstetrics Clinic, Masaryk University and Teaching Hospital
      Brno. METHOD: Forty seven women with a growth retardation of the fetus diagnosed
      before delivery who gave birth in the Teaching Hospital in Brno during 2003-2005
      and intrapartal ST analysis of fetus ECG was subsequently used, were enrolled
      into this prospective study (group A). The control group consisted of 87
      deliveries taking place in the same period of time and concerning women with
      fetuses suffering from growth retardation and monitored by standard methods
      (group B). The standard methods included cardiotocography (CTG), supplemented
      with pulse oximetry (IFPO) if needed. The diagnosis of intrauterine fetus growth
      retardation was established on the basis of the results of repeated prepartal
      ultrasound fetus biometry with estimation of the mass, which corresponded to a
      group below 10 percentile for the given gestational age. The numbers of vaginal
      deliveries and surgically treated delivery due to threatening fetus hypoxia
      (Cesarean section, forceps delivery) were recorded. The authors evaluated
      postpartal pH from umbilical artery, independently for the group of values of pH
      < 7.00, the group of pH 7.00-0.10 and pH 7.10 or more. The values of Apgar score
      were evaluated for the first, fifth and tenth minute, respectively. The
      neonatologist followed the duration of stay of the newborn at the Newborn
      Intensive Care Unit, the Intermediate Care Unit, total duration of
      hospitalization, the occurrence of sepsis in the early newbotn period, the
      occurrence of hyperbilirubinemia, and the conclusion of neurological examination.
      All the results were evaluated statistically by the chi2 test, Kruskal-Wallis
      test or the Anova method. RESULTS: There was no statistically significantly
      difference in the number of delivery ended by surgery for threatening fetus
      hypoxia (p = 0.856) or the detection rate of intrapartal hypoxia according to pH
      values of umbilical blood divided into the three groups (p = 0.657, p = 0.958, p
      = 0.730, respectively). The values of Apgar score differed in favor of the group
      A significantly only in the first minute at the level of 5% opf significance (p =
      0.018). The values of Apgar score in the fifth and tenth minute did not show any
      significant difference (P = 0301 and p = 0313, respectively). There was no
      statistically significant difference in neonatological results between the group
      A and B. CONCLUSION: The use of ST analysis of fetal ECG in the course of
      delivery of fetuses with presumed intrauterine growth retardation did not show
      any significant difference from the presently used methods (CTG supplemented with
      IFPO if needed). In using the method there was not any effect on the number of
      surgically treated deliveries for indications of threatening acute fetus hypoxia
      or perinatal results and postnatal adaptation of the newborns.

PMID- 16956037
TI  - [Actual management of pregnancies at risk for fetal anemia].
AB  - OBJECTIVE: To evaluate the utilisation measurements of peak systolic velocities
      in the middle cerebral artery (MCA-PSV) to predict the degree of fetal anemia and
      to find out whether implementation of MCA-PSV into management of pregnancies at
      risk for fetal anemia enable to reduce the number of invasive procedures. DESIGN:
      A prospective study. SETTING: Department of Obstetrics and Gynecology, Department
      of Medical Genetics and Fetal Medicine, Neonatology Department, University
      Hospital, Olomouc. METHODS: In 81 pregnancies at risk for fetal anemia MCA-PSV
      had been assessed and fetal blood sampling for measurement of hemoglobin
      concentration was obtained subsequently, either by cordocentesis or at delivery.
      The values of MCA-PSV and hemoglobin concentration were expressed as multiples of
      median (MoM). Anemia was defined as mild (hemoglobin <0.84 MoM) for a given
      gestational age, moderate (hemoglobin <0.65 MoM), and severe (hemoglobin <0.55
      MoM). The number of cordocenteses performed in previous conventional management
      of pregnacies at risk for fetal anemia was compared with management by Doppler
      measurement of MCA-PSV. RESULTS: 313 examinations were performed at 17-38 week's
      gestation. An MCA-PSV >1.5 MoM detected 100% of severly anemic fetuses with a
      hemoglobin concentration <0,65 MoM that required invasive intervention. In 27
      cases a cordocentesis was performed and intrauterine blood transfusion was given
      alternatively. Remaining fetuses did not require invasive intrauterine
      intervention and no or mild hemolytic anemia and hyperbilirubinemia were
      diagnosed after delivery. Overall sensitivity to detect moderate to severe anemia
      (hemoglobin <0.65 MoM for a given gestational age) was 100%. Specificity was 92%,
      positive predictive value was 60% and negative predictive value was 100%. One
      false positive case was identified after 35 weeks. In 2002 at least one
      cordocentesis was performed in all pregnancies at risk for fetal anemia 100%, in
      2003 78%, in 2004 20% and in 2005 20%. At least one cordocentesis with
      intrauterine blood transfusion was required by only 24% of all fetuses at risk
      for fetal anemia. The other fetuses 76% (34/45) didn't require intrauterine
      transfusion. CONCLUSION: Middle cerebral artery peak systolic velocity is a
      highly sensitive non-invasive means for determining the degree of fetal anemia
      and implementation of MCA-PSV into management of pregnancies at risk for fetal
      anemia enable to reduce the number of invasive procedures. This parameter should
      not yet be considered the global standard of care for diagnosis of fetal anemia
      because incorrect use by an unexperienced operator may cause more harm than good.
      However, if there is a reasonably close medical center with sonographers tranined
      to assess the MCA-PSV, patients at risk for fetal anemia should be reffered to
      this center.

PMID- 16956038
TI  - [Rapid detection of most frequent chromosomal aneuploidies by the multiplex QF
      PCR method in the first trimester of pregnancy].
AB  - OBJECTIVE: Rapid detection of most frequent aneuploidies by the multiplex QF PCR
      method in non-cultured samples of chorial tissue. Summarized results of QF PCR
      method applied in the management of care of pregnant women in the first trimester
      of pregnancy. TYPE OF STUDY: An original contribution. SETTING: Institute of
      Medical Genetics and Fetal Medicine, Faculty Hospital and Medical Faculty,
      Palacky University Olomouc. METHODS: The samples of chorial tissue were obtained
      from 101 pregnant women. Non-cultured samples were processed by the multiplex QF
      PCR method. STR loci of chromosomes 13, 18, 21 and X and Y were analyzed. These
      markers were amplified in two separate multiplex PCR reactions under the same
      conditions and subjected to fragmentation analysis in capillary electrophoresis.
      RESULTS: All 101 analyzed samples of chorial tissue were successfully amplified.
      In this group, 16 pathologies of the fetuses were detected by the multiplex QF
      PCR method. Triploidy was detected in two cases, trisomy of chromosome 21--Down
      syndrome was found in seven cases, and trisomy of chromosome 18--Edwards syndrome
      was found in six cases and monosomy of gonosome X--the Turner' s syndrome was
      revealed once. CONCLUSIONS: The multiplex QF PCR method is an indispensable part
      of the screening of the first trimester and provides a rapidly available and
      reliable result in the examined patients.

PMID- 16956039
TI  - [Birth defects' occurrence in offspring of mothers taking 1st trimester
      medication in the Czech Republic in 1996-2004].
AB  - OBJECTIVE: An analysis of birth defects incidence in offspring of mothers taking
      1st trimester medication in the Czech Republic in 1996-2004. TYPE OF STUDY: A
      retrospective demographical-epidemiological analysis of data from a National
      Register of Congenital Anomalies of the Czech Republic. METHODOLOGY: Data on
      birth defects in the Czech Republic from the Institute of Health Information and
      Statistics--National Register of Congenital Anomalies from the 1996-2004 period
      and a control group data on healthy children born to mothers taking medications
      from the same time period. Data on medication were analyzed in relation to
      particular defects and were also used in international databases. RESULTS: There
      were 1,125 children born with a birth defect to mothers taking 1st trimester
      medication making a total of 1,456 particular birth defects. A control group
      covered 1,321 exposed women giving birth to a child without any birth defect.
      Some types of congenital heart defects, cleft lip with cleft palate and limb
      reduction defects. A significantly higher risk was found also in following 5
      types of drugs: anticoagulants, antihypertensives, peripheral vasodilatants,
      urologics and antiepileptics. CONCLUSIONS: A significantly higher risk was found
      for the following defects: anencephaly, spina bifida, congenital hydrocephalus,
      anophthalmia/microphthalmia and auricular and limb reduction defects. Although
      the results are not always unambiguous and are probably influenced by both
      information and recall bias, they complement data on adverse effects of drugs in
      pregnancy in the Czech Republic. They also stress the need for a high preliminary
      caution in drug prescription and for a complex and individual risk assessement by
      a clinical geneticist.

PMID- 16956040
TI  - [Birth defects occurrence and their role in perinatal mortality in the Czech
      Republic in 2004].
AB  - OBJECTIVE: An analysis of birth defects occurrence in the Czech Republic in 2004
      and a comparison to data from 1996-2003. TYPE OF STUDY: A retrospective analysis
      of data from a National Register of Congenital Anomalies of the Czech Republic.
      METHODOLOGY: Data on birth defects in the Czech Republic from the Institute of
      Health Information and Statistics--National Register of Congenital Anomalies from
      the 1996-2004 period were used. An analysis of incidence of selected type of
      birth defects was performed along with their contribution to perinatal mortality
      according to particular types of defects. RESULTS: There were 29 186 children
      born with a birth defect, out of it were 17,063 boys and 12,116 girls, an
      undetermined sex was reported in 7 cases. A mean incidence of birth defects 2004
      in was 367.9/10,000 live births. Corresponding data from years 2003, 2002 and
      2001 were 405.2, 4043 and 407.9/10,000 live births. CONCLUSIONS: Current data on
      birth defects in 2004 in the Czech Republic are presented with a comparison to a
      8-year period. An analysis of temporal and demographic changes in birth defects
      incidence is given along with data on birth defects contribution to perinatal
      mortality in selected types of defects.

PMID- 16956041
TI  - [Sentinel lymph nodes identification in vulvar cancer--methods and technique].
AB  - OBJECTIVE: To evaluate detection of sentinel lymph nodes (SLN) in squamous vulvar
      cancer with blue dye and 99mTc. The study describes technique of application,
      timing, management, detection rate (DR), specific side detection rate (SSDR) and
      false negative rate. DESIGN: Prospective clinical study. SETTING: Department of
      Obstetrics and Gynecology, Charles University Prague, 2nd Medical Faculty,
      Teaching Hospital Motol. PATIENTS AND METHODS: 46 women with squamous cell
      carcinoma tumors stage I or II, <4 cm with no clinical suspect lymph nodes were
      included. Blue dye alone was used in 16 women and the combination of 99mTc and
      blue dye was used in 30 women. Radiocoloid 99mTc was applied 3-5 hours and blue
      dye 3-5 minutes prior to ingvinal incision. RESULTS: We detected 88 SLN in 61
      inguinal spaces. The detection rate in the blue dye group was 68.8 % (11 cases).
      One false negative SLN (6.3 %) appeared in this group. In blue dye+ 99mTc group
      detection rate was 100 % with no false negative SLN. CONCLUSION: Detection of SLN
      in squamous vulvar cancer with the combination of 99mTc and blue dye was
      statistically significantly more effective than using the blue dye alone.

PMID- 16956042
TI  - [Fertility sparing surgery in early cervical cancer today and tomorrow].
AB  - OBJECTIVE: Describtion and evaluation of proposed protocol for conservative,
      fertility sparing surgeries in the treatment of early stages of cervical cancer
      and its comparison to most frequently used protocols regarding its reproductive
      and oncological outcomes. DESIGN: Prospective clinical study. SETTING: Department
      of Obstetrics and Gynecology, Charles University Prague, 2nd Medical Faculty,
      University Hospital Motol. PATIENTS AND METHODS: 24 patients that fitted into the
      inclusion criteria were recruited in the study (6 in stage T1A2 and 18 T1B1).
      Inclusion criteria were: tumor less than 20 mm in largest diameter, less than 1/2
      of the stromal invasion, SCC serum levels within normal range, signed informed
      consent. Minimum follow up was 24 months. Described therapeutic protocol,
      evaluation of oncological and reproductive outcomes and comparison with different
      fertility sparing regimens were performed. RESULTS: In four cases (16.7%)
      peroperative histopatghological evaluation (frozen section: FS) detected
      metastatic involvement of lymphatic nodes. In one case (4.1%) following 14 months
      since initial surgery, reccurent disease in uterine isthmus was detected. The
      patient underwent chmotherapy and she is 36 months in complete remission. In the
      series of 15 women planning pregnancy 11 subjects become pregnant so far. Eight
      deliveries occurred (one in 24th week of gestation--650g, one in 34w--2240g, one
      in 36w--2700g and five between 37-39w). Only one newborn was delivered in the
      cathegory of extreme prematurity. CONCLUSION: Sentinel node detection involving
      peroperative histopathological evaluation followed by subsequent serial
      processing and together with 2-step therapeutic management increases efectivity
      of fertility sparing surgeries. Less radical surgery on uterine cervix:
      reconisaton (in stage IA2) or simple trachelectomy (in early stage T1B1) with
      negative finding after laparoscopic lymph node dissection has comparative results
      with radical trachelectomy and abdominal radical trachelectomy. Pregnancy rates
      and pregnancy outcomes particularly regarding in term delivery is the best after
      treatment of early stages of cervical cancer using proposed protocol, while very
      promising results are published in studies with radical vaginal trachelectomy as
      well. Results published for the patients treated with abdominal radical
      trachelectomy are unsatisfactory.

PMID- 16956043
TI  - [Chemotherapy intensity importance in concurrent chemoradiotherapy of locally
      advanced cervical cancer].
AB  - OBJECTIVE: Concurrent chemoradiotherapy with weekly cisplatin became a standard
      procedure in patients with locally advanced cervical carcinoma. The objective of
      this retrospective study was to evaluate the therapy toleration and the survival
      of patients with locally advanced cervical cancer treated with concurrent
      chemoradiotherapy with weekly cisplatin of 40mg/m2. SUBJECT AND METHOD: From
      January 2000 to December 2004, 40 patients with locally advanced cervical cancer
      were treated with concurrent chemoradiotherapy with weekly cisplatin of 40mg/m2.
      Radical radiotherapy consisted of external beam radiotherapy 25 x 2 Gy to the
      pelvis, high-dose rate brachytherapy 6 x 4 Gy to the tumor, boost 7 x 2 Gy to the
      pelvic walls. 21 patients also recieved 22 x 2 Gy to the para-aortic lymphatic
      nodes. RESULTS: Only 16 patients recieved full five doses of cisplatin. Causes of
      discontinuance of the chemotherapy: acute hematological toxicity with leukopenia
      (10), thrombocytopenia (1), anaemia (1), increased levels of creatinine (2),
      profuse vomiting (1), haematemesis (1). Stage dependent two-year overall survival
      (OS) was 72% (IIB) against 64% (III, IVA). Two-year disease-free survival (DFS)
      dependent on the number of cisplatin doses was 77% (> or = 3 doses) against 56%
      (<3 doses) in patients with IIB stage. CONCLUSION: Acute hematological toxicity
      with leukopenia was the most frequent cause of discontinuance of the
      chemotherapy. The results of two-year OS and DFS show difference in dependence on
      the number of applied doses of chemotherapy. However, the difference was not
      significant due to a low number of patients subject to the study.

PMID- 16956044
TI  - [Lysophosphatidic acid in ovarian cancer patients].
AB  - OBJECTIVE: To compare plasma lysophosphatidic acid (LPA) level in ovarian cancer
      patients and women without ovarian pathology. DESIGN: Prospective study. SETTING:
      Department of Gynecology and Obstetrics, University Hospital, Hradec Kralove.
      METHODS: The method for LPA level analyze with its specification by capillary
      electrophoresis using indirect ultraviolet detection has been implementated.
      Since the beginning of this project venous blood samples from 103 patients (60
      patients with ovarian cancer, 43 patients without ovarian pathology) have been
      obtained. RESULTS: Plasma LPA levels were elevated in ovarian cancer patients
      (sigma LPA Med 19.9 micromol/l, Range 4.5-42.7 micromol/l). Patients without
      ovarian pathology (n=35) (sigma LPA Med 2.6 micromol/l, Range 0.9-22.9
      micromol/l, P<0,001) had statistically significant lower plasma LPA level
      compared with ovarian cancer patients. CONCLUSION: Lysophosphatidic acid appears
      useful as diagnostic marker of ovarian cancer.

PMID- 16956045
TI  - [Birth injury of the puborectalis muscle--3D ultrasound evaluation].
AB  - OBJECTIVE: Evaluation of the influence of vaginal childbirth on the integrity of
      the puborectalis muscle with the help of real-time 3D ultrasound. DESIGN:
      Prospective pilot study. SETTING: Institute for Care for Mother and Child,
      Prague, Czech Republic. MATERIAL AND METHODS: We examined 20 primigravid women in
      the third trimester and on the third day after vaginal delivery. The
      transperineal 3D ultrasound examination was performed and the data were evaluated
      afterwards in the 4D view software. The VCI (Volume Contrast Imaging) mode with
      slice thickness 3 millimeters was used for analysis. We evaluated the integrity
      of the puborectalis muscle on both sides, the quality of the images and the
      presence of hematomas. RESULTS: The examination before delivery did not show any
      abnormal anatomy of the examined region. We found four (20%) unilateral defects
      and one (5%) bilateral puborectalis avulsion after the delivery. The bilateral
      defect was after the forceps delivery, the other defects occurred after normal
      uncomplicated vaginal deliveries, where only left mediolateral episiotomy was
      performed and the birth weight did not exceed 3700 g. In our series, 25% of women
      suffered an injury of a major muscle of pelvic floor. No defect was diagnosed
      during the delivery and did not show any connection with the episiotomy.
      CONCLUSIONS: 3D ultrasound can detect major birth trauma to the puborectalis
      muscle. The puborectalis muscle avulsion is usually not recognized during the
      delivery and does not cause immediate problem to the patient.

PMID- 16956046
TI  - [Results of conservative surgery of uterine fibroids--5 years of follow-up].
AB  - OBJECTIVE: To evaluate the outcome of the myomectomy. DESIGN: Prospective study.
      SETTING: Gynecology-Obstetrics Ward, Regional Hospital Pardubice. METHODS: The
      group consists of 147 patients with uterine fibroid (or fibroids) in which was
      performed myomectomy from September 1997 till December 2001. Myomectomy was
      performed by hysteroscopy, laparoscopy, laparotomy or by posterior colpotomy. The
      mean age was 40.1 years. We evaluated short term (during the first year) and long
      term (after 5 years) outcomes including the pregnancy outcome. SHORT TERM
      OUTCOMES: During the 1st year 135 (91.84%) patients were without complications
      and satisfied with their status after the procedure. LONG TERM OUTCOMES: After 5
      years 121 (82.31%) patients were without problems or reoperation. From the group
      of the women with the desire of the pregnancy the pregnancy rate was 71.05%.
      Deliveries of the viabile foetus were 77.78%. 38.10% delivieries were performed
      by Caesarian Section. CONCLUSION: At present it is often necessary to treat
      uterine fibroids without hysterectomy. We have several surgical approaches
      including the minimally invasive techniques that may be succesfull and the
      results may be satisfactory for most of the patients.

PMID- 16956047
TI  - ["See and treat" hysteroscopy: limits of intrauterine pathology bulk].
AB  - OBJECTIVE: To evaluate bulk limits of intrauterine pathology for "see and treat"
      hysteroscopy. TYPE OF STUDY: A retrospective observational study. SETTING:
      Department of Gynaecology and Obstetrics, First Faculty of Medicine, Charles
      University Prague and General Teaching Hospital Prague. METHODS: 200 mg of
      Indomethacin was administered to the patients by rectum 2 hours before procedure.
      "See and treat" procedures were performed with "Versascope" in awake patients
      without any peroperatively admistered analgesia or anaesthesia. As a "see and
      treat" were managed 796 endometrial polyps, 125 submucous myomas, as well as 62
      cases of intrauterine synechias. CONCLUSIONS: endometrial polyps up to 1,5 cm,
      pedunculated submucous myomas up to 1,0 cm as well as fibroid adhesiones
      obliterated no more than 1/3 of uterine cavity can be managed as "see and treat"
      procedures with a high compliance of the patients.

PMID- 16956048
TI  - [Etiopathogenesis of the prolapsed vaginal vault after hysterectomy].
AB  - OBJECTIVE: To determine the main etiopathogenic factors which may participate in
      the development of vaginal prolapse after hysterectomy. DESIGN: A retrospective
      study. SETTING: Department of Obstetrics and Gynecology, Medical Faculty of the
      Palacky University and University Hospital, Olomouc. METHODS: The analysis of
      relevant factors which can participate in the origin and development of vaginal
      prolapse was carried out on the group of 51 patients treated for vaginal prolapse
      after hysterectomy performed in the years 2002 to 2005. The data were retrieved
      retrospectively from medical documentation and appended by the information
      obtained from questionnaires send to the patients. RESULTS: Factors participating
      in the development of vaginal prolapse can be divided into 3 groups: 1. Mistakes
      in surgical technique and complications in the post-operative period, 2.
      inherited qualities of patients, and 3. impact of adverse external factors.
      CONCLUSIONS: Several factors are involved in the etiopathogenesis of vaginal
      prolapse, the most important of which are the inherited qualities of patients,
      incorrect surgical technique and adverse outcome in the post-operative period.

PMID- 16956049
TI  - [Gynecological aspects of thyroid disorders. A review].
AB  - OBJECTIVE: The most frequent thyroid syndromes--hypothyroidism and thyrotoxicosis
      -are often accompanied with menstrual disturbances. The aim of this study was to
      summarize knowledge of physiology, pathology and clinical aspects of both
      thyroidal and gonadal axis interactions. SUBJECT: A review. SETTING: Department
      of Pathological Physiology, 1st Faculty of Medicine, Charles University, Prague.
      CONCLUSION: About 25% female infertility and 15% menstrual cycle disorders result
      from thyroid dysfunction. Particularly, the subclinical hypothyroidism has a high
      prevalence in the population; therefore, thyroid function must be examined in
      female with unclear infertility or menstrual disturbances. The next overlap of
      thyroid disorders and gynaecology represents iodine-131 use for differentiated
      thyroid carcinoma in fertile age with aspects to ovarian failure and gestational
      risk.

PMID- 16956050
TI  - [Assisted reproduction in patients with food intake disorders--clinical and
      ethical aspects].
AB  - Fertilization treatment is established therapy of infertility in the cases, where
      other approaches have failed or were impossible. In eating disorders, majority of
      fertility problems has been secondary and so fully reversible if appropriately
      treated. Fertilization treatment should not be used in patients refusing the
      psychological treatment of the illness. In patients in active phase of the
      illness fertility treatment at fertility are contra-indicated. Two cases of
      negative impact of fertility treatment in patients with anorexia nervosa are
      presented.

PMID- 16956051
TI  - [Present occurrence of benign teratoma of ovary and fallopian tube in a patient
      with adnexal torsion].
AB  - OBJECTIVE: The authors demonstrate the case of left adnexal torsion caused by 2
      benign teratomas in its ovarian and tubal location. DESIGN: Case report. SETTING:
      Department of Obstetrics and Gynecology, 1st Faculty of Medicine and General
      Teaching Hospital, Charles University, Prague. CASE: 24-years old woman underwent
      laparoscopy for several days lasting pain in lower abdomen and ultrasound finding
      of semicystic mass in the left adnexal region with suspicion of teratoma. The
      benign teratoma of the left ovary together with a torsion of the left Fallopian
      tube distended by teratoma was revealed during surgery. Left side salpingectomy
      and enucleation of the ovarian teratoma has been performed. This surprising
      finding was confirmed by histopathological examination. CONCLUSION: The acute
      gynaecological torsion event may be caused not only by torsion of uterine fibroid
      or enlarged tumorous ovary but rarely also by a teratoma of the Fallopian tube.

PMID- 16956052
TI  - [Massive breast angiomatosis with dramatic course leading to acute total
      mastectomy--a case report].
AB  - OBJECTIVE: On the background of clinical, radiological and morphologic settings
      presented is unusual case of the rare angiomatosis of the female breast.
      Discussed are both clinicopathological aspects and differential diagnosis from
      the morphological point of view. DESIGN: Case report. SETTING: Biopsy Lab s.r.o.
      and Sikl's Department of Pathology, Charles University and Faculty Hospital,
      Pilsen. METHODS: As a case report described is a rare case of the angiomatosis of
      the female breast. Implemented illustrations consist of local findings, CT scan,
      specimen gross appearance and histological pictures including
      immunohistochemistry. Applied antibodies and detection system LSAB+ were provided
      by Dako, visualization was performed by chromogen DAB (diaminobenzidin
      tetrahydrochlorid). RESULTS: 30-year-old woman suffering of painful, enormous
      breast asymmetry underwent core needle biopsy of the right breast. The mastogram
      showed diffuse process of ambiguous significance. During the next few days her
      condition dramatically changed and under the circumstances of florid apoplexy and
      suspicion of tumor of her right breast, total mastectomy was carried out.
      Histological picture revealed widespread, unlimited vascular lesion dissecting
      throughout the stroma of the entire gland. Bland morphology and the nature of
      tissue involvement eventually led to diagnosis of benign angiomatosis. The woman
      underwent several local plastic operations but is out of final reconstruction of
      her breast so far. Thirteen months after mastectomy there are no signs of
      recurrence.

PMID- 16956053
TI  - [Vulval oedema as the first sign of Crohn's disease--case reports].
AB  - OBJECTIVE: To show a rare reason of vulval oedema. DESIGN: Case report. SETTING:
      Department of Obstetrics and Gynecology, General Faculty Hospital, 1st Faculty of
      Medicine, Charles University Prague. SUBJECT AND METHOD: Oedema of vulva is
      presented in three case reports as form of cutaneous Crohn's disease. It causes
      mistakes of diagnosis and therapy. CONCLUSION: Oedema of vulva as a sign of
      vulval Crohn's disesase can appear even several years before intestinal problems.

PMID- 16956054
TI  - [Harmatoma of the breast--case report].
AB  - OBJECTIVE: To describe rare hamartoma of the breast in a 31-year-old female.
      DESIGN: Case report. SETTINGS: Department of Special Diagnostics SPAU, Charles
      University Hospital Pilsen. SUBJECT AND METHOD: A 31-year-old female was examined
      for breast asymmetry. A huge tumor was revealed in right mammary gland using
      ultrasonography. Encapsulated tumor 10x10x10 cm was removed. Subsequent
      histological examination revealed breast hamartoma. The patient is alive and well
      without signs of disease one year after excision. CONCLUSION: Hamartoma of the
      breast is a rare benign tumor. Diagnostics is very complicated and it is almost
      impossible to establish correct diagnosis preoperatively. A simple excision is a
      sufficient treatment with good curative effect.

PMID- 16956055
TI  - [Molecular prognostic factors and pathogenesis of endometrial cancer].
AB  - OBJECTIVE: To evaluate the importance of molecular markers for prognosis and
      pathogenesis of endometrial carcinoma. DESIGN: A review article. SETTING:
      Department of Medical Genetics and Fetal Medicine, University Hospital, Olomouc,
      Department of Obstetrics and Gynecology, University Hospital, Olomouc. METHODS:
      This article reviews the current knowledge of the molecular changes in the
      development of endometrial cancer, and their possible importance for the
      patient's prognosis. CONCLUSION: The new molecular biomarkers are apparently
      going to play a significant role in the management of endometrial carcinoma
      treatment in the near future.

PMID- 16956056
TI  - White-spot syndrome virus (WSSV) introduction into the Gulf of Mexico and Texas
      freshwater systems through imported, frozen bait-shrimp.
AB  - We analysed 20 boxes of, frozen imported bait-shrimp (China: Parapenaeopsis sp.
      and Metapenaeopsis sp.) and 8 boxes of native, frozen bait-shrimp (Gulf of
      Mexico: Litopenaeus setiferus and Farfantepenaeus duorarum) by RT-PCR or PCR for
      Taura syndrome virus (TSV), yellowhead virus/gill-associated virus (YHV/GAV),
      white-spot syndrome virus (WSSV) and infectious hypodermal and hematopoietic
      necrosis virus (IHHNV). All 28 boxes of shrimp were negative for TSV, YHV/GAV and
      IHHNV; 2 boxes of imported bait-shrimp were WSSV-positive by 3 different PCR
      assays. Intramuscular injection of replicate groups of SPF (specific pathogen
      free) L. vannamei juveniles with 2 different tissue homogenates prepared from the
      2 WSSV-positive bait boxes resulted in 100% mortality of the test shrimp within
      48 to 72 h post-injection. No mortality occurred among injected negative control
      groups. Histological and in situ hybridization analyses of 20 moribund treatment
      shrimp demonstrated severe WSSV infections in each sample. Oral exposure of SPF
      L. vannamei postlarvae, PL (PL 25 to 30 stage; approximately 0.02 g) to minced
      tissue prepared from the 2 WSSV-positive bait-lots did not induce infection,
      possibly because of an insufficient infectious dose and/or viral inactivation
      resulting from multiple freeze-thaw cycles of the bait-shrimp during PCR testing.
      Use of an electric drill and collection of drill-tailings (tissue from
      approximately 20 to 30 shrimp) from frozen blocks of shrimp was successfully
      employed as an alternate tissue-sampling method without thawing. Our findings
      indicate that imported WSSV-infected bait shrimp, originating from China, are
      being sold in Texas for the purpose of sport fishing and represent a potential
      threat to freshwater and marine crustacean fisheries, as well as to coastal US
      shrimp farms.

PMID- 16956057
TI  - Occurrence of Anguillicola crassus (Nematoda: Dracunculoidea) in Japanese eels
      Anguilla japonica from a river and an aquaculture unit in SW Taiwan.
AB  - The infection by swimbladder nematodes of the genus Anguillicola (Dracunculoidea:
      Anguillicolidae) was examined in 2 populations of the Japanese eel Anguilla
      japonica in SW Taiwan. Wild eels from the Kao-Ping river were compared with
      cultured eels from an adjacent aquaculture unit. Only the cosmopolitan species
      Anguillicola crassus was present. Among wild eels, prevalence of infection varied
      between 21 and 62%, and mean intensity between 1.7 and 2.7 for adult worms.
      Similar intensity values (1.3 to 2.8) were recorded for the larvae. In cultured
      eels, prevalence as well as mean intensities were higher. In the cultured hosts,
      mean larval intensities exceeded those of adult worms 2-fold, and maximum larval
      intensities were 4- to 5-fold higher than in eels from the river. In cultured
      eels, dead larvae were also more abundant than in wild eels. We conclude that
      infrapopulations of A. crassus in Japanese eels are regulated by the defense
      system of this host, intraspecific density-dependent regulation being less likely
      as the major regulatory mechanism. No influence of the parasite on eel condition
      was found in either wild or cultured eels, indicating a low or moderate
      pathogenic effect of A. crassus on this host. This study shows that A. crassus is
      moderately common in cultured and wild Japanese eels in Taiwan, where the
      parasite is endemic.

PMID- 16956058
TI  - Application of a real-time PCR assay to detect and quantify the myxozoan parasite
      Ceratomyxa shasta in river water samples.
AB  - Ceratomyxa shasta is a virulent pathogen of salmonid fishes that is enzootic in
      the Pacific Northwest of North America. Current parasite detection methods
      involve sentinel fish exposures that are laborious and time-consuming. As a
      substitute, a filtering protocol and a quantitative real-time TaqMan polymerase
      chain reaction (QPCR) assay were developed to detect and enumerate parasite
      spores in river water. Fluorescence was detected from both the myxospore and
      actinospore stages of the parasite but not from the fish or polychaete hosts or
      from 9 other myxozoans tested. Less than 1/1000th of a spore was detected,
      indicating each had >1000 copies of the target 18S rRNA gene. The assay detected
      1 spore in 1 l river water. Inhibition of the assay by some river samples was
      overcome by reducing the template volume and including bovine serum albumin in
      the reaction; occasionally a second purification step was required. The QPCR
      methodology was utilised to investigate the temporal and spatial distribution of
      C. shasta in the Klamath River, Oregon/ California. The parasite was detected
      throughout the river, and 2 of 5 tributaries tested contributed parasites to the
      mainstem. Correlation of QPCR cycle threshold values with a standard curve for
      known starting numbers of whole spores revealed several sites where parasite
      abundance was in excess of 20 spores l(-1). Although QPCR data corroborated
      results of sentinel fish exposures, spore numbers did not correlate consistently
      with mortality in the exposure groups. The water sampling and filtering protocol
      combined with the QPCR assay is a simple and relatively rapid method for
      detection and quantification of parasite levels in environmental water samples.

PMID- 16956059
TI  - Identification of genetic markers associated with Gyrodactylus salaris resistance
      in Atlantic salmon Salmo salar.
AB  - Gyrodactylus salaris Malmberg, 1957 is a freshwater monogenean ectoparasite of
      salmonids, first recorded in Norway in 1975 and responsible for extensive
      epizootics in wild Atlantic salmon Salmo salar L. The susceptibility of different
      populations of Atlantic salmon to G. salaris infection differs markedly, with
      fish from the Baltic being characterised as relatively resistant whereas those
      from Norway or Scotland are known to be (extremely) susceptible. Resistance to
      Gyrodactylus infection in salmonids has been found to be heritable and a
      polygenic mechanism of control has been hypothesised. The current study utilises
      a 'Quantitative trait loci' (QTL) screening approach in order to identify
      molecular markers linked to QTL influencing G. salaris resistance in B1
      backcrosses of Baltic and Scottish salmon. Infection patterns in these fish
      exhibited 3 distinct types; susceptible (exponential parasite growth), responding
      (parasite load builds before dropping) and resistant (parasite load never
      increases). B1 backcross fish were screened at 39 microsatellite markers and
      single marker-trait associations were examined using general linear modelling. We
      identified 10 genomic regions associated with heterogeneity in both innate and
      acquired resistance, explaining up to 27.3% of the total variation in parasite
      loads. We found that both innate and acquired parasite resistance in Atlantic
      salmon are under polygenic control, and that salmon would be well suited to a
      selection programme designed to quickly increase resistance to G. salaris in wild
      or farmed stocks.

PMID- 16956060
TI  - Viability, infectivity and fatty acid synthetic activity of Perkinsus marinus
      meront cells incubated in estuarine and artificial seawater.
AB  - We investigated the viability and fatty acid synthetic activity of in vitro
      cultured Perkinsus marinus (Dermo) in lipid-free medium and estuarine water, and
      the infectivity of P. marinus maintained in artificial seawater (ASW). Viability
      and fatty acid synthetic activity in 7 d old P. marinus meronts maintained in
      lipid-free medium and estuarine water were tested. The infectivity of meronts
      incubated in ASW was examined by first incubating P. marinus meronts in ASW for
      2, 3 or 7 d, and then inoculating viable ASW-incubated meronts into the shell
      cavity of individual oysters Crassostrea virginica. P. marinus infection
      prevalence and intensity in oysters were determined 9 wk post-inoculation. Heavy
      mortality occurred in meronts maintained in estuarine water, a drop from an
      initial value of 100% viable to 7.8 and 6.1% after 3 and 14 d incubation,
      respectively. Viability was 85 and 67% in meronts maintained in lipid-free medium
      for 3 and 24 d, respectively. Meronts kept in lipid-free medium for 14 d retained
      their ability to synthesize fatty acids. Viable meronts incubated in ASW remained
      infective for up to 7 d. The infection prevalences were 85, 48 and 100%, in the
      treatments inoculated with viable meronts that were incubated in ASW for 2, 3 and
      7 d, respectively. Infection prevalence in the group inoculated with viable
      meronts immediately after they were transferred to ASW ranged from 61 to 85%. Our
      results suggest that in nature meronts can survive for at least 14 d outside the
      host. Viable meronts are not only infective, but are also able to replicate and
      retain their fatty acid synthetic ability for 7 d.

PMID- 16956061
TI  - Techniques for detecting chytridiomycosis in wild frogs: comparing histology with
      real-time Taqman PCR.
AB  - Chytridiomycosis is a lethal disease of amphibians associated with mass
      mortalities and population declines worldwide. An accurate, non-invasive
      technique for detecting chytridiomycosis is urgently needed to determine the
      current geographical distribution of the disease, and its prevalence in wild
      amphibian populations. Herein we evaluate a recently devised, rapid, non
      invasive, swab-PCR assay. We sampled 101 wild juvenile Mixophyes iteratus by both
      a skin swab for use in PCR analysis, and a toe-clip for examination by
      histological methods. The swab-PCR assay detected chytridiomycosis infection in a
      minimum of 14.9% of frogs, whereas histology detected infection in no more than
      6.9% of frogs. We conclude that the swab-PCR technique is the more reliable means
      of detecting chytridiomycosis in wild amphibians, and that it precludes the need
      for toe-clipping as a means of sampling for the presence of the disease in future
      surveys. Further, we document a significant negative relationship between a
      juvenile frog's snout-vent length and its likelihood of being infected with the
      disease.

PMID- 16956062
TI  - Cost efficiency in the detection of chytridiomycosis using PCR assay.
AB  - Chytridiomycosis is an emerging infectious disease of amphibians associated with
      mass mortalities and population declines worldwide. Recent technological advances
      have resulted in a highly sensitive, non-invasive technique for diagnosing the
      disease based on a quantitative (real-time) polymerase chain reaction (qPCR)
      assay. The qPCR assay yields the most accurate and informative data of any
      available detection technique. However, due to the relatively high costs
      involved, it has yet to attain widespread use by chytridiomycosis researchers.
      Using the results of a disease survey of 467 wild frogs from eastern Queensland,
      Australia, we examine the necessity of triplicate assays in qPCR detection of
      chytridiomycosis. We describe a singlicate qPCR assay that can be used to
      substantially decrease costs, with no significant decrease in sensitivity. We
      also demonstrate that detection of chytridiomycosis by use of the conventional
      PCR assay may lead to appreciable underestimations in disease prevalence. We
      recommend that amphibian disease researchers adopt the singlicate qPCR assay as
      the primary means of chytridiomycosis detection.

PMID- 16956063
TI  - Polychlorinated biphenyls and organochlorine pesticide levels in tissues of
      Caretta caretta from the Adriatic Sea.
AB  - We detected concentrations of polychlorinated biphenyls (PCBs) and organochlorine
      pesticides (OCs) in the liver, muscle, and fat of 11 loggerhead sea turtles
      Caretta caretta from the central and southern Adriatic Sea. All samples contained
      PCBs at various concentrations, with Congener 138 (28%), 153 (27%), and 180 (32%)
      dominating the congener composition of the tissues. The dioxin-like congener
      (118, 13%) was detected in all tissues analyzed. The lower-chlorinated PCBs were
      not detected. The average of the total PCB concentrations, expressed in nanograms
      per gram wet weight, was 459.6 ng g(-1) in fat, 82.9 ng g(-1) in liver, and 5.8
      ng g(-1) in muscle. Among 13 organochlorine pesticides for which analyses were
      conducted, 4 were detected: p,p'-DDE (57%); p,p'-DDD (16%); and p,p'-DDT and o,p'
      DDT (27%). Spatial differences were found among OC concentrations in loggerheads
      from the central and southern Adriatic Sea. The only samples containing
      detectable concentrations of p,p'-DDT and o,p'-DDT were from the southern area.

PMID- 16956064
TI  - Aplysina red band syndrome: a new threat to Caribbean sponges.
AB  - A substantial and increasing number of reports have documented dramatic changes
      and continuing declines in Caribbean coral reef communities over the past 2
      decades. To date, the majority of disease reports have focused on scleractinian
      corals, whereas sponge diseases have been less frequently documented. In this
      study, we describe Aplysina red band syndrome (ARBS) affecting Caribbean rope
      sponges of the genus Aplysina observed on shallow reefs in the Bahamas. Visible
      signs of disease presence included 1 or more rust-colored leading edges, with or
      without a trailing area of necrotic tissue, such that the lesion forms a
      contiguous band around part or all of the sponge branch. Microscopic examination
      of the leading edge of the disease margin indicated that a cyanobacterium was
      consistently responsible for the coloration. Although the presence of this
      distinctive coloration was used to characterize the diseased state, it is not yet
      known whether this cyanobacterium is directly responsible for disease causation.
      The prevalence of ARBS declined significantly from July to October 2004 before
      increasing above July levels in January 2005. Transmission studies in the
      laboratory demonstrated that contact with the leading edge of an active lesion
      was sufficient to spread ARBS to a previously healthy sponge, suggesting that the
      etiologic agent, currently undescribed, is contagious. Studies to elucidate the
      etiologic agent of ARBS are ongoing. Sponges are an essential component of coral
      reef communities and emerging sponge diseases clearly have the potential to
      impact benthic community structure on coral reefs.

PMID- 16956065
TI  - Virus-like particles associated with mass mortalities of the pen shell Atrina
      pectinata in Japan.
AB  - Mass mortalities of the pen shell Atrina pectinata occurred in the fishing
      grounds of Ariake Bay, in southwestern Japan, during late spring and summer in
      2003 and 2004. Histological examination revealed extensive necrosis in the
      epithelial cells of the kidney and gill, and impairment of the endothelial cells
      of the mantle arteria. Although cestode larvae belonging to the genus
      Tylocephalum were found in the mantle, adductor muscle, kidney, and digestive
      gland, their prevalence and the intensity of infection were low. Examinations of
      moribund pen shells for Haplosporidium spp. infection using PCR analysis and for
      Perkinsus spp. infection using Ray's fluid thioglycollate medium were negative.
      Unenveloped virus-like particles were detected by transmission electron
      microscopy in the cytoplasm of affected kidney and gill cells of moribund pen
      shells. They were icosahedral spherical and 50 to 55 nm in diameter. These virus
      like particles found in moribund pen shells are different from those described in
      other marine mollusks, and may be the causative agent of the mass mortalities of
      pen shells.

PMID- 16956066
TI  - Effect of hyperthermia on the replication of white spot syndrome virus (WSSV) in
      Procambarus clarkii.
AB  - The effect of hyperthermia on the development of white spot syndrome virus (WSSV)
      in the crayfish Procambarus clarkii was studied by competitive PCR. Crayfish were
      exposed to different temperatures (24 +/- 1 and 32 +/- 1 degrees C) after WSSV
      injection. No mortality was observed when crayfish were held at 32 +/- 1 degrees
      C, but mortality reached 100% when crayfish were transferred to 24 +/- 1 degrees
      C. Competitive PCR showed that viral levels at 32 +/- 1 degrees C remained at
      10(5) copies mg(-1) tissue, while at 24 +/- 1 degrees C levels were significantly
      higher, rising from 10(4) to 10(10) copies mg(-1) tissue. These results suggest
      that hyperthermia reduces viral replication, but does not eliminate viral
      particles from WSSV-infected crayfish.

PMID- 16956067
TI  - Antiviral Chemistry & Chemotherapy's current antiviral agents FactFile 2006 (1st
      edition).

PMID- 16956068
TI  - Antiviral Chemistry & Chemotherapy's current antiviral agents FactFile 2006 (1st
      edition).
AB  - The number of useful antiviral compounds is rapidly expanding. The current
      antiviral agents FactFile is a convenient key to the vital statistics of
      antiviral compounds to be used as an aide memoire when reading or writing
      antiviral literature. A mini-portrait is provided for each of the antiviral
      compounds. The minimum criteria for inclusion of new compounds in the FactFile is
      the granting of an investigational new drug application with the realistic
      potential for medical or veterinary application. Several compounds that were
      subsequently withdrawn from further development are also included because of
      their historical importance or particular interest. The compounds are listed
      alphabetically according to their generic names together with systematic chemical
      names, common names and chemical structures. The compounds are grouped by virus
      targets; thus, the list is sub-divided into inhibitors of DNA viruses, RNA
      viruses, and retroviruses. The authors welcome comments and suggestions to be
      incorporated in future editions of the FactFile.

PMID- 16956070
TI  - Nurse prescribers are not rewarded for this new responsibility.

PMID- 16956069
TI  - Patient protection puts nurses at risk.

PMID- 16956071
TI  - Building the case for CAM.

PMID- 16956072
TI  - Drink problem.

PMID- 16956073
TI  - Being prepared for redeployment.

PMID- 16956074
TI  - An overview of the new NICE guidelines on bipolar disorder.
AB  - Bipolar disorder can be a debilitating long-term condition characterised by
      extreme mood swings, ranging from elation to severe depression and sometimes
      coexisting mixtures of the two. This article looks at new guidance from NICE
      (2006) that provides recommendations for nurses on the assessment, treatment and
      long-term management of bipolar disorder.

PMID- 16956075
TI  - Anatomy and function of the skin. Part 4--Appendages.

PMID- 16956076
TI  - Best practice in management of patients with acute stroke.
AB  - The management of the patient with acute stroke is very complex and covers all
      aspects from acute intervention to ensuring a dignified and pain-free death.
      Stroke has an increasing profile and with the proposed NICE paper on best
      practice due out in the next 18 months, the focus will be on the effective
      running of stroke units and the skills of nurses who work in them. It is
      essential that nurses keep up to date with developments and know how to provide
      the best, evidence-based care.

PMID- 16956077
TI  - Developing antenatal classes for women with HIV infection.
AB  - As numbers of new HIV infections rise, innovative means of healthcare delivery
      for this patient group are being sought. This article describes the running of
      antenatal classes for pregnant women with HIV infection in a south-east London
      hospital, which aim to reduce mother-to-child HIV transmission. Led by a
      community-based clinical nurse specialist, the initiative adopts a
      multidisciplinary team approach.

PMID- 16956078
TI  - A reflective account of a trip to escort a sick patient overseas.
AB  - Reflection can be used to look back over events and to turn them into learning
      experiences. This article is a personal, reflective account of using Gibbs' model
      to debrief and learn following a trip to Australia, escorting a sick patient.

PMID- 16956079
TI  - Teenagers' use of condoms.

PMID- 16956080
TI  - [Old and new: trends in geriatric psychiatry].

PMID- 16956081
TI  - [Somatic investigation of psychiatric patients newly admitted to Flemish general
      psychiatric hospitals].
AB  - BACKGROUND: In Flanders there is as yet very little consensus concerning the
      extent and content of somatic investigations available to and conducted on
      patients newly admitted to psychiatric hospitals. AIM: To obtain an overview of
      the numbers and specialisms of medical-somatic staff at Flemish general
      psychiatric hospitals, the equipment available and the somatic routine
      examinations regularly requested. METHOD: We compiled a questionnaire about
      current hospital policy concerning the diagnosis of physical illnesses in newly
      admitted patients and the availability of diagnostic facilities. We submitted the
      questionnaires to 20 Flemish psychiatrist hospitals. RESULTS: The commonest type
      of medical equipment available at these psychiatric hospitals consisted of ECG, X
      ray and ultrasonic devices. The routine examinations that were requested most
      frequently were blood and urine tests, ECG'S, clinical examinations, and X-rays
      of the thorax. The numbers and specialisms of somatic doctors at these hospitals
      vary from one hospital to the next. Sometimes a hospital does not have any
      somatic doctors at all. CONCLUSION: The general psychiatric hospitals in Flanders
      do not have a uniform policy concerning somatic examinations on newly admitted
      patients. The equipment and the numbers and specialisms of the medical-somatic
      staff vary from one hospital to another. It seems reasonable that extra
      investigations such as blood tests, ECG's and thorax X-rays should be conducted
      when case histories and clinical examinations indicate that such testing may be
      useful.

PMID- 16956082
TI  - [Residual neuropsychological, structural and functional brain abnormalities after
      long-term cannabis use].
AB  - BACKGROUND: An important question that arises in policy discussions concerning
      the use of cannabis is whether the possible harmful effects of cannabis are
      reversible. AIM: To review studies on residual neuropsychological, structural and
      functional brain abnormalities that may have resulted from the long-term use of
      cannabis. METHOD: When we searched Medline (January 1966 - December 2003) and
      EMBASE (January 1988 - December 2003) using the key words 'cannabis',
      'marijuana', 'neuropsychological test', 'cognition', 'CT-scan', 'MRI', 'PET',
      'SPECT' and 'brain', we found 29 studies in our area of interest. We selected
      only those neuropsychological and functional brain imaging studies in which the
      patients had a controlled abstinence period longer than 98 hours. RESULTS: On the
      basis of six studies we concluded that there was insufficient evidence to prove
      conclusively that long-term cannabis use causes or does not cause residual
      abnormalities. The results of our review were also inconclusive whether cannabis
      use during adolescence may have a lasting effect on cognitive functioning and
      brain structure. However, we could not rule out the possibility that (1) certain
      cognitive and cerebral abnormalities existed in patients before cannabis use
      began and (2) that patients were suffering from subacute effects of cannabis.
      CONCLUSION: So far, research into the residual effects of cannabis use has been
      inadequate. Future studies should concentrate on the effect of cannabis use
      during early adolescence. More insight should come from longitudinal studies
      involving neuropsychological measurements and brain imaging before cannabis use
      begins. The abstinence period should be at least seven weeks.

PMID- 16956083
TI  - [Epidemiology of panic].
AB  - BACKGROUND: There is uncertainty about the clinical relevance of panic disorder
      and subsyndromal panic disorder. AIM: To assess the clinical relevance ofpanic
      disorder and subsyndromal panic disorder. METHOD: We searched Medline and
      PsycINFO for population studies performed as from 1980. We used as search terms:
      'general population', 'psychiatr', 'prevalence' and 'panic'. On the basis of the
      studies found we compiled a review of the epidemiology of panic which enabled us
      to assess the clinical relevance. RESULTS: The life time prevalence of panic
      disorder is 2.1%; subsyndromal panic disorder is more prevalent (limited symptom
      attacks 7.5%, infrequent panic attacks 5.1%). Lifetime psychiatric comorbidity is
      high. The risk and symptom profile for panic disorder and subsyndromal panic
      disorder is the same. The course of both disorders is unfavourable. There is an
      increased risk that someone with panic disorder will develop a depression;
      subsyndromal panic disorder is a non-specific precursor of psychopathology. Both
      panic disorder and subsyndromal panic disorder are associated with attempted
      suicide, deficiencies and the use of the health care services, even after
      comorbidity has been corrected for. CONCLUSION: It is incorrect only to label
      panic symptoms 'pathological' if they satisfy the DSM criteriafor panic disorder;
      both panic disorder and subsyndromal panic disorder are clinically relevant.

PMID- 16956084
TI  - [Dissociative symptoms and sleep].
AB  - There is a widespread view among psychiatrists that dissociative experiences such
      as depersonalisation, derealisation, absorption, and psychogenic amnesia have a
      traumatic etiology. This view is subjected to a critical evaluation. We also
      discuss an alternative interpretation namely that dissociative experiences are
      caused by a labile sleep-wake rhythm. We evaluated this alternative view in two
      exploratory studies. In study 1 we looked at the relationship between the
      Dissociative Experience Scale (DES) and the Iowa Sleep Experiences Survey (ISES)
      and in study 2, we checked this relationship when the response bias was
      controlled for. Dissociative experiences (measured with the DES) correlated with
      the ISES. The correlation between DES and ISES remained completely intact even
      when we controlledfor response bias. Our findings show that dissociative symptoms
      are associated with typical sleep experiences such as nightmares and strange
      dreams. The association is not the by-product of the positive response bias which
      generally characterises persons with dissociative symptoms.

PMID- 16956085
TI  - [Stabilisation therapy as an answer to complex post-traumatic stress disorder.
      Diagnosis, treatment and research in women abused in childhood with a complex
      post-traumatic stress disorder].
AB  - Complex post-traumatic stress disorder resulting from traumatic experiences in
      childhood includes not only the customary post-traumatic stress disorder symptoms
      such as intrusions, avoidance and hyperarousal, but it also includes affect
      dysregulation, dissociation, problems with self-image, relationships,
      interpretation and somatisation. The specialist literature expresses some support
      for stabilisation treatment. Preliminary results of a pilot study that evaluated
      a stabilisation course with a psycho-educational and cognitive behavioural
      content indicate that a course of that kind, if linked to research, is both
      feasible and effective. We therefore believe that further research by means of a
      randomized controlled trial is warranted.

PMID- 16956086
TI  - [Recent findings regarding the treatment of late-onset depression with vascular
      brain lesions. A literature review].
AB  - BACKGROUND: Late-onset depression with vascular brain lesions is showing
      increased resistance to antidepressive pharmacotherapy. AIM: To give an overview
      of alternative treatment options. METHOD: We conducted a literature search via
      PubMed using the key words: 'late-onset depression', 'white matter lesions',
      'cerebrovascular pathology' and 'treatment' and thereby a searchfor all available
      clinical studies about the treatment described in combination with the key words
      'vascular depression', or 'late-onset depression' and 'white matter lesions'.
      RESULTS: Electroconvulsive therapy, repetitive transcranial magnetic stimulation
      and nimodipine au,gmentation have beneficial effects on vascular depression.
      CONCLUSION: The treatment options mentioned are promising, but there is a need
      for further clinical studies.

PMID- 16956087
TI  - [Galactorrhoea and the use of selective serotonin reuptake inhibitors].
AB  - The subject of this case study is a female patient who was treated with a
      selective serotonin reuptake inhibitor (SSRI), citalopram, because of a
      depressive episode. She developed symptoms of galactorrhea; there was a time
      relationship between suspension of the treatment with citalopram and a reduction
      of the galactorrhea symptoms. The consulting internist assumed that the symptoms
      were due to hyperprolactinemia arising from under-supplementation of thyroid
      hormone and resultant hypothyroidism. Psychiatrists usually see galactorrhea in
      patients who are taking antipsychotics. However, few psychiatrists know that
      galactorrhea can also be caused by SSRIs. When a patient has symptoms of
      bilateral galactorrhea and has used an SSRI and when hyperprolactinemia has been
      found in laboratory tests it is probably advisable to stop the SSRI medication.
      The article mentions what additional research is needed.

PMID- 16956088
TI  - [Benzodiazepines in the treatment of catatonia].
AB  - A patient who developed acute catatonia during benzodiazepine withdrawal is
      discussed. The case prompted us to review the literature on the role of
      benzodiazepines in the treatment of acute catatonia. Only retrospective and open
      studies were found which indicate that benzodiazepines do have a beneficial
      effect. Lorazepam is the most widely studied benzodiazepine and at present is the
      best treatment option. In the specific case of acute catatonia brought on by
      benzodiazepine withdrawal the recommended dosage is the same as for acute
      catatonia caused by something other than benzodiazepine withdrawal.

PMID- 16956089
TI  - [Reaction to "What we can learn from Jip and Janneke. About comparison in the
      psychiatry" and "Back to Griesinger"?].

PMID- 16956091
TI  - [A mistake in the Dutch shortened DSM-IV guideline was apparently also not
      noticed in the revision of DSM-IV-TR].

PMID- 16956090
TI  - [Reaction to "A critical analysis about the diagnostic choice for schizophrenia
      as starting point of practice guidelines for treatment"].

PMID- 16956092
TI  - Cognitive technologies for gist processing.
AB  - Cognitive technologies extend our cognitive abilities, yet they are currently
      deficient in many respects. According to fuzzy-trace theory, people are gist
      processors with a fuzzy-processing preference, and information is mentally
      represented along a fuzzy-to-verbatim continuum. An understanding of gist
      processing could form the basis of a new generation of more effective cognitive
      technologies. This suggests, first, the need for new tools to help Web page
      creators optimize gist representations of text. Such a system could provide
      feedback about the visitor's gist and make recommendations about rewriting. It
      also suggests the need for new tools to help authors create more effective means
      of presenting quantitative data in visual form. The advocated approach
      capitalizes on the collective knowledge of communities of practice on the Web.
      Finally, it suggests the need for new tools for collecting input from users. The
      facial composite system EvoFIT is cited as an example.

PMID- 16956093
TI  - Word frequency effects in high-dimensional co-occurrence models: A new approach.
AB  - The HAL (hyperspace analog to language) model of lexical semantics uses'global
      word co-occurrence from a large corpus of text to calculate the distance between
      words in co-occurrence space. We have implemented a system called HiDEx (High
      Dimensional Explorer) that extends HAL in two ways: It removes unwanted influence
      of orthographic frequency from the measures of distance, and it finds the number
      of words within a certain distance of the word of interest (NCount, the number of
      neighbors). These two changes to the HAL model produce measures of word
      neighborhood density that are reliably predictive of human lexical decision
      reaction times.

PMID- 16956094
TI  - Anagram software for cognitive research that enables specification of
      psycholinguistic variables.
AB  - Anagram tasks are frequently used in cognitive research, and the generation of
      new scrambled letter combinations is a task well suited to a software solution.
      Most available programs, however, do not allow experimenters to generate new
      anagrams flexibly or to characterize existing anagrams using psycholinguistic
      criteria. They also do not provide detailed information on their source
      dictionaries. We present anagram software that interfaces with CELEX2, an
      internationallyrecognized psycholinguistic database. This software allows users
      to capitalize on lexical variables and thus enables direct control of
      psycholinguistic features that may influence the cognitive processes involved in
      anagram solution.

PMID- 16956095
TI  - Language history questionnaire: A web-based interface for bilingual research.
AB  - A Web-based interface has been developed to facilitate researchers in collecting
      language history information online. Most researchers use their own versions of
      language history questionnaires for specific studies in second language
      acquisition. Although these versions of questionnaires all differ from one
      another in some respects, there is a significant amount of overlap between them.
      Here we identify the crucial dimensions that most investigators consider
      important to include in such a questionnaire. We have examined the most commonly
      asked questions in 41 published questionnaires, and on the basis of our analyses
      we propose a general L2 language history questionnaire. Subjects can enter some
      or all of the information on the Web, and the results are automatically generated
      as an RTF output file on the user's desktop.

PMID- 16956096
TI  - Typing versus thinking aloud when reading: implications for computer-based
      assessment and training tools.
AB  - The goal of this study was to assess the impact of modality of production of
      think-aloud protocols on reading strategies. Readers in two studies spoke or
      typed protocols for narrative or science texts and completed comprehension tests
      for each text. Human judges identified the presence of paraphrasing, bridging
      inferences, and elaborating within the protocols. Reading comprehension skill was
      assessed with the Nelson-Denny test. With respect to narrative texts,
      paraphrasing and bridging were less frequent when readers were typing than when
      they were thinking aloud. With respect to science texts, less-skilled readers
      made bridging inferences more frequently when typing than when speaking.
      Conversely, skilled readers generated more paraphrases than bridges when typing
      thoughts but not when speaking. These results have implications for computer
      based tools for reading assessment and intervention.

PMID- 16956097
TI  - NUANCE 3.0: using genetic programming to model variable relationships.
AB  - Previously, we introduced a new computational tool for nonlinear curve fitting
      and data set exploration: the Naturalistic University of Alberta Nonlinear
      Correlation Explorer (NUANCE) (Hollis & Westbury, 2006). We demonstrated that
      NUANCE was capable of providing useful descriptions of data for two toy problems.
      Since then, we have extended the functionality of NUANCE in a new release (NUANCE
      3.0) and fruitfully applied the tool to real psychological problems. Here, we
      discuss the results of two studies carried out with the aid of NUANCE 3.0. We
      demonstrate that NUANCE can be a useful tool to aid research in psychology in at
      least two ways: It can be harnessed to simplify complex models of human behavior,
      and it is capable of highlighting useful knowledge that might be overlooked by
      more traditional analytical and factorial approaches. NUANCE 3.0 can be
      downloaded from the Psychonomic Society Archive of Norms, Stimuli, and Data at
      www.psychonomic.org/archive.

PMID- 16956098
TI  - Creating partially deleted objects for perception research.
AB  - Line drawings are commonly used in perception research. A basic strategy used in
      such research is to remove portions of the line drawings in order to determine
      what features of an object are important for recognition. However, it is
      important to monitor the amount of contour and type of information that are
      deleted when one is making partially deleted or fragmented objects. With the
      Image Fragmenting Program, researchers can use random or manual contour deletion
      strategies to create fragmented objects while controlling for the amount of
      contour removed from the images.

PMID- 16956099
TI  - An evaluation of response allocations to concurrently available slot machine
      simulations.
AB  - Gambling behavior often involves making choices between concurrently available
      game options. With regard to slot machine gambling, multiple games allow for
      choices to be made with respect to which game to play. The authors of the present
      study used a slot machine simulation created in Visual Basic.NET to examine
      gambling preference. The specific question addressed was whether gamblers prefer
      a smaller payout more often (averaging around every 10 spins) over a larger
      payout less often (averaging around every 50 spins). Two types of reinforcement
      were examined during the study: frequency of payouts and the amount of credits
      won. The results indicate that participants had a preference for a slot machine
      with the more frequent payout as opposed to one with more intermittent payout.
      These results support existing literature on theories of choice and provide a
      step toward understanding human gambling behavior.

PMID- 16956100
TI  - Transformation of flow in rehabilitation: the role of advanced communication
      technologies.
AB  - Authentic rehabilitation requires the active participation of patients and their
      involvement with opportunities for action and development. Within this framework,
      in this article we outline the possibility of using two emerging computing and
      communication technologies-ambient intelligence (AmI) and virtual reality (VR)-
      for a new breed of rehabilitative and clinical applications based on a strategy
      defined as transformation of flow. Transformation of flow is a person's ability
      to exploit an optimal (flow) experience to identify and use new and unexpected
      psychological resources as sources of involvement. We identify the feeling of
      presence--the feeling of being in a world that exists outside oneself--as the
      theoretical link between the technology and rehabilitation. AmI and VR are used
      to trigger broad empowerment processes induced by a strong sense of presence,
      leading to greater agency and control over one's actions and environment.

PMID- 16956101
TI  - SCiP at 35: an idiosyncratic history of the society for computers in psychology.
AB  - SCiP history may be divided into three eras: the Paleozoic (1971-1982), the
      Mesozoic (1982-1994), and the Cenozoic (1994-present). Following a list of
      Secretary-Treasurers, a list of all SCiP Presidents is provided in Table 1. Next
      I present personal highlights, including the first symposium on psychology and
      the World-Wide Web; David Rumelhart's mathematical explanation of connectionism;
      and Stevan Hamad's discussion of "freeing" the journal literature. I observe that
      a small conference is becoming more intimate and that much of our mission
      involves figuring out how to conduct high-quality scientific research with
      consumer-grade electronics. I argue that we are an increasingly international
      organization, that graduate students are welcome, and that we should become more
      inclusive in the areas of gender and ethnicity and should make membership more
      meaningful I conclude by looking ahead and attempting to predict the future.

PMID- 16956102
TI  - A quantitative measure for the uniformity of fixation density: The Voronoi
      method.
AB  - In order to characterize the uniformity of fixation density, we propose
      aquantitative measure based on Voronoi diagrams, in which cells are defined
      around fixation locations. We examined how normalized cell size distributions are
      related to homogeneous and inhomogeneous fixation densities. Two possible
      measures for use with the Voronoi method are discussed. Both show good
      correlation with subjective visual evaluations of the uniformity of fixation
      densities. Not only are these measures objective and quantitative, they also have
      a simple intuitive meaning: They may be thought of as reflecting the clustering
      of fixations.

PMID- 16956103
TI  - Evaluation of unsupervised semantic mapping of natural language with Leximancer
      concept mapping.
AB  - The Leximancer system is a relatively new method for transforming lexical co
      occurrence information from natural language into semantic patterns in a
      nunsupervised manner. It employs two stages of co-occurrence information
      extraction-semantic and relational-using a different algorithm for each stage.
      The algorithms used are statistical, but they employ nonlinear dynamics and
      machine learning. This article is an attempt to validate the output of
      Leximancer, using a set of evaluation criteria taken from content analysis that
      are appropriate for knowledge discovery tasks.

PMID- 16956104
TI  - Tscope: A C library for programming cognitive experiments on the MS windows
      platform.
AB  - Tscope is a C/C+ + programming library designed for programming experiments that
      run on Windows 2000/XP. It is intended for a public of experimental psychologists
      with moderate programming skills, who are accustomed to writing their own
      experimental programs for DOS but have not made the step to Windows-based
      programming yet. It provides molecular functions for graphics, sound, timing,
      randomization, and response registration. Together with ANSI-C standard library
      functions and the powerful C syntax, this set of functions gives the experimenter
      the opportunity to program virtually any experiment one can come up with. Tscope
      is completely based on free software, is distributed under the GNU General Public
      License, and is available at expsy.ugent.be/tscope. An integrated development
      environment for compiling and running Tscope programs is also freely available.

PMID- 16956105
TI  - Eye and pen: A new device for studying reading during writing.
AB  - We present a new method for studying reading during writing and the relationships
      between these two activities. The Eye and Pen device makes a synchronous
      recording of handwriting and eye movements during written composition. It
      complements existing online methods by providing a fine-grained description of
      the visual information fixated during pauses as well as during the actual writing
      act. This device can contribute to the exploration of several research issues,
      since it can be used to investigate the role of the text produced so far and the
      documentary sources displayed in the task environment. The study of the
      engagement of reading during writing should provide important information about
      the dynamics of writing processes based on visual information.

PMID- 16956106
TI  - Picture-naming norms for Canadian French: name agreement, familiarity, visual
      complexity, and age of acquisition.
AB  - The present study provides Canadian French normative data for 388 line drawings
      from the European Picture Pool for Oral Naming (Protocole europeen de
      denomination orale d'images; PEDOI; Kremin et al., 2003). One hundred eighty
      subjects were equally distributed for age group (18-39,40-59, 60-85), educational
      level (low, high), and sex. They rated pictures of objects on age of acquisition,
      name agreement, familiarity, and visual complexity. Syllable length and word
      frequency were also taken into account. The present study suggests that age of
      acquisition and name agreement show significant age-related differences. These
      results show that unequivocal interpretation of age-related differences can be
      made when age-appropriate norms are used.

PMID- 16956107
TI  - A low-cost, MR-compatible olfactometer.
AB  - We present a design for an olfactometer, suitable for fMRI experiments, that can
      be constructed at extremely low cost. The olfactometer presents odors directly to
      the nose via a nasal cannula at unobtrusively low flow velocities, with no large
      assemblies required on or near the subject's face. The olfactometer can be
      controlled manually, or by computer via a serial interface. A validation study
      verified that the olfactometer reliably presents odors to test subjects. Errors
      and response latency times decreased with increased flow rate in an orderly
      manner, as expected.

PMID- 16956108
TI  - Using self-reported data to assess the validity of driving simulation data.
AB  - In this article, we use self-reported driving behaviors from a written
      questionnaire to assess the measurement validity of data derived from a driving
      simulation. The issue of validity concerns the extent to which measures from the
      experimental context map onto constructs of interest. Following a description of
      the experimental methods and setting, an argument for the face validity of the
      data is advanced. Convergent validity was assessed by regressing behaviors
      observed in thedriving simulatoron self-reported measures of driving behaviors.
      Significant relationships were found across six measures: accidents, speeding,
      velocity, passing, weaving between traffic, and behavior at stop signs.
      Concurrent validity was evaluated with an analysis of simulator accident
      involvement and attention deficit hyperactivity disorder status. Discriminant
      validity was assessed using a multitrait-multimethod matrix of simulator and
      questionnaire data. We concluded that although the relationship between self
      reported behaviors and observed responses in the simulator falls short of perfect
      correspondence, the data collected from the driving simulator are valid measures
      of the behaviors of interest.

PMID- 16956109
TI  - Pocket-sized psychology studies: exploring daily diary software for palm pilots.
AB  - Daily dairies, also known as experience sampling methods (ESM) or everyday
      experience methods, are a common methodology utilized to provide insight into
      momentary psychological processes. Traditionally, such studies often have
      utilized paper-and-pencil surveys administered several times each day over a span
      of several days or weeks. However, advances in technology now allow these studies
      to be conducted using palmtop computers (i.e., personal digital assistants;
      PDAs). Three software packages for running these studies on the Palm operating
      system were explored and compared on a number of features Specifically, ESP
      (Experience Sampling Program, by Feldman Barrett & Barrett, 2001), iESP Version
      3.2 (Intel Experience Sampling Program, by Intel Research Seattle & the
      University of Washington Computer Science and Engineering Department), and PMAT
      Version 2.0 (Purdue Momentary Assessment Tool, by the Military Family Research
      Institute at Purdue University) were examined, with their key features compared.
      These advances in software for running diary studies include a number of features
      that provide researchers with methods and information previously unavailable in
      diary studies and may expand the range of possibilities in diary study designs.

PMID- 16956110
TI  - Investigating systematic individual differences in sleep-deprived performance on
      a high-fidelity flight simulator.
AB  - Laboratory research has revealed considerable systematic variability in the
      degree to which individuals' alertness and performance are affected by sleep
      deprivation. However, little is known about whether or not different populations
      exhibit similar levels of individual variability. In the present study, we
      examined individual variability in performance impairment due to sleep loss in a
      highly select population of militaryjet pilots. Ten active-duty F-117 pilots were
      deprived of sleep for 38 h and studied repeatedly in a high-fidelity flight
      simulator. Data were analyzed with a mixed-model ANOVA to quantify individual
      variability. Statistically significant, systematic individual differences in the
      effects of sleep deprivation were observed, even when baseline differences were
      accounted for. The findings suggest that highly select populations may exhibit
      individual differences in vulnerability to performance impairment from sleep loss
      just as the general population does. Thus, the scientific and operational
      communities' reliance on group data as opposed to individual data may entail
      substantial misestimation of the impact of job-related stressors on safety and
      performance.

PMID- 16956111
TI  - An SPSS implementation of the nonrecursive outlier deletion procedure with
      shifting z score criterion (Van Selst & Jolicoeur, 1994).
AB  - Sophisticated univariate outlier screening procedures are not yet available in
      widely used statistical packages such as SPSS. However, SPSS can accept user
      supplied programs for executing these procedures. Failing this, researchers tend
      to rely on simplistic alternatives that can distort data because they do not
      adjust to cell-specific characteristics. Despite their popularity, these simple
      procedures may be especially ill suited for some applications (e.g., data from
      reaction time experiments). A user friendly SPSS Production Facility
      implementation of the shifting z score criterion procedure (Van Selst &
      Jolicoeur, 1994) is presented in an attempt to make it easier to use. In addition
      to outlier screening, optional syntax modules can be added that will perform
      tedious database management tasks (e.g., restructuring or computing means).

PMID- 16956112
TI  - Power analysis for multivariate and repeated measurements designs via SPSS:
      correction and extension of D'Amico, Neilands, and Zambarano (2001).
AB  - D'Amico, Neilands, and Zambarano (2001) published SPSS syntax to perform power
      analyses for three complex procedures: ANCOVA, MANOVA, and repeated measures
      ANOVA. Unfortunately, the published SPSS syntax for performing the repeated
      measures analysis needed some minor revision in order to perform the analysis
      correctly. This article presents the corrected syntax that will successfully
      perform the repeated measures analysis and provides some guidance on modifying
      the syntax to customize the analysis.

PMID- 16956113
TI  - Stem cell therapy for demyelinating disorders.
AB  - Multiple sclerosis (MS) is a progressive disease of the central nervous system
      (CNS) that attacks mainly young people. It leads to the progressive deterioration
      of the neurological status. Histopatologically, this disease is characterized by
      appearance of multiple foci of the demyelination in white matter of the CNS, with
      various grade of an axonal loss. The current treatment is targeted on moderating
      the inflammatory process and symptomatic therapy. In spite of all this therapy,
      the course of the disease often progresses. The tissue of the CNS in mammalians,
      including humans, is able to provide some degree of spontaneous remyelination.
      Unfortunatelly the extent of this process is not sufficient for the complete
      restoration. The support of remyelination by using the cell manipulations is the
      aim of many experimental studies. Theoretically, it is possible to achieve
      remyelination either by exogenous induction of remyelination from endogenous
      sources (precursor cells) or by the real transplantation of myelin-forming cells
      intrafocally, intracerebroventricularly or into the blood stream. In this work,
      we present the brief view on the recent state of this topic. We present the list
      of the cell types, useable for cell transplantations and the summary of the
      growth factors influencing the behaviour of the oligodendroglial precursors. We
      are considering the hampers in usage of the cell therapy of demyelinating
      disorders in clinics.

PMID- 16956114
TI  - Evaluation of the success of beta-tricalciumphosphate and deproteinized bovine
      bone in maxillary sinus augmentation using histomorphometry: a review.
AB  - Sinus lift operations have become a prerequisite for implantologists in the
      rehabilitation of atrophic posterior maxilla. Alloplasts and xenografts are the
      recent innovation in the world of grafting materials and have evolved in such a
      way as to compensate the need for autografts to be used in conjunction. In order
      to perfect the grafting materials, histomorphometry is the most often tool used
      to study the success of the augmentation. This article has tried to commemorate
      the importance of histomorphometry in maxillary antroplasty and also the success
      rate of beta-tricalciumphosphate and deproteinized bovine bone as an augmentation
      material in maxillary augmentation.

PMID- 16956115
TI  - Root resorption in relation to orthodontic tooth movement.
AB  - Root resorption is an undesirable sequela of orthodontic tooth movement. The
      odontoclasts are responsible for root resorption and the process of hyalinization
      is known to preceed the orthodontic root resorption. It is found that there are
      several predisposing factors, therefore an evaluation of these factors should be
      done by careful examination of personal medical history, severity of malocclusion
      and dental treatment (if any due to previous history of trauma), anterior
      crossbite etc. The evaluation becomes an essential factor as it helps the
      orthodontists in detecting the occurance and severity of the root resorption and
      thereby plan out the treatment more effectively. Orthodontic tooth movements
      especially intrusion and other movements like tipping, torque are all known to
      influence the root resorption, therefore the detection using radiographs and
      repair of root resorption is of utmost significance as root resorption is a more
      serious problem from a medicolegal stand point of view. However some studies have
      shown that the repair process is known to occur after the cessation of
      orthodontic treatment by the deposition of cementum of cellular type. In the
      light of orthodontist's liability of what is basically an unpredictable
      phenomenon, it is necessary that the speciality define this uncertainity and
      protect its members against unnecessary and unjustified litigation.

PMID- 16956116
TI  - The effects of pesticide exposure on serum total sialic acid levels.
AB  - Pesticides used to increase agricultural production have hazard effects for human
      being health. The present study reports the serum levels of total sialic acid
      (TSA) in the pesticide applicators in the agriculture areas of the Kahramanmaras,
      Turkiye. This study included a total of 79 volunteer individuals. Pesticide group
      included 47 men who were working as pesticide applicators. Control group
      comprised healthy males (n=32), nonsmokers and nondrinkers and also nonexposured
      to pesticide and other chemicals chronically. Serum TSA level was measured with
      the Warren method modified by Ponnio et al. The TSA concentrations were
      significantly higher in the pesticide groups (p < 0.001) than those of control
      subjects. We can conclude from the results obtained that serum TSA was affected
      by pesticide exposure. This finding may be an indication of harmful effects of
      pesticides. Increased serum TSA levels in pesticide exposure might be related to
      various diseases e.g. various cancers, which are also often associated with
      elevated serum TSA levels. However further studies are necessary to evaluate the
      concentrations of serum TSA in pesticide exposure.

PMID- 16956117
TI  - Serum adenosine deaminase activity in monitoring disease activity and response to
      therapy in severe psoriasis.
AB  - OBJECTIVES: Activity of Serum Adenosine Deaminase (ADA), a main enzyme in purine
      degradation and considered as a marker for non-specific T cell activation, in
      psoriasis has been investigated in a few studies with conflicting results. DESIGN
      AND METHODS: To evaluate the significance of serum ADA activity in psoriasis, and
      analyze whether ADA activity may be related to disease activity, we performed a
      prospective study with 38 cases of psoriasis and 24 healthy volunteers. Patients
      were divided into two groups as cases with local and stable lesions (Group i, n:
      20) and severe cases with extensive involvement (Group ii, n: 18). Serum ADA
      activity was determined by modified Guisti procedure. RESULTS: When taken into
      consideration of all patients--regardless of the severity of the disease--the
      mean serum ADA activity of psoriatics did not differ significantly from that of
      controls (p > 0.05). However, it was higher in Group ii than in Group i and
      healthy controls (respectively p < 0.001 and p < 0.05). A significant decrease
      was observed also after therapy only in Group ii (p < 0.001). CONCLUSION: Serum
      ADA activity may be correlated to the disease activity of severe psoriasis. We
      suggest that it might be a serologic marker for follow-up of in such cases. It
      could be used in predicting relapses before clinical findings as well as in
      deciding to stop or decrease systemic therapies at the right time, which have
      potential to cause severe systemic side effects when given for a long period.
      Further studies with larger case populations are required to support our
      findings.

PMID- 16956118
TI  - A 5-year experience of a minimally invasive technique for correction of pectus
      excavatum in Croatia.
AB  - The aim of this study was to assess the results of 5-year experience with
      minimally invasive operation without medial incision and resection cartilages for
      correction of pectum excavatum. From 2000 we made in our Hospital minimally
      invasive technique for the correction of pectus excavatum. 75 patients were
      treated by minimally invasive technique. A convex steel bar is inserted under the
      sternumtrough small bilateral Incisions. The steel bar is inserted with the
      convexity facing posteriorly, and when it is in position, the bar is turned over.
      After 2 years the bar is removed when permanent remolding has occurred. Initial
      excelent results were maintained in 54 patients (normal chest), good results in
      16 (mild residual pectus) and poor in 5 (severe recurrence requiring further
      treatment). The mean follow-up since surgery were 3 months to 3 years. Average
      blood loss was 25 ml. Average length of hospital stay was 8 days. Patients
      returned to full activity after 2 month. Complications were pneumothorax in 12
      patients, pneumonia in 6 patients and displacement of the steel barr requiring
      revision in 2 patients. Poor results occurred because steel bar was too soft in 3
      patients, and soft sternum in 2 patients with Marfan's syndrome. The minimally
      invesive technique is effective without cartilage incision and resection or
      sternal osteotomy.

PMID- 16956119
TI  - Renal tubular impairment in children with idiopathic hypercalciuria.
AB  - Idiopathic hypercalciuria (IH) is defined as hypercalciuria that persists after
      correction of dietary inbalances and has no detectable cause. The excretion of
      urinary N-acetyl-beta-D-glucosaminidase (U-NAG), a marker of proximal tubular
      damage, has been previously reported as either increased or normal in children
      with IH. We evaluated U-NAG in 20 children (13 boys and 7 girls, mean age 10.3
      years +/- 5.7 SD) with IH (urinary calcium excretion above 0.1 mmol/kg/24 hours,
      with no detectable cause) and with otherwise normal renal function tests.
      Ultrasound examination revealed urolithiasis (n=4) and nephrocalcinosis (n=1).
      The U-NAG values were evaluated in the spot urine collected from the second
      morning void and calculated as the urinary NAG/creatinine ratio (U-NAG/Cr) and
      expressed in nkat/mmol. The 24-hour urinary calcium excretion (U-Ca/24h) was
      assessed in a urinary sample from 24-hour collected urine and calculated in
      mmol/kg. The obtained results of U-Ca/24h and U-NAG/Cr were expressed as Z
      scores. When compared to the reference data, the U-Ca/24h and U-NAG/Cr were
      significantly higher (p = 0.0004 and p = 0.006, respectively). There was no
      correlation between the U-NAG/Cr and U-Ca/24h (r = 0.18, p = 0.20). The U-NAG/Cr
      values were significantly higher in the 5 patients with
      urolithiasis/nephrocalcinosis, whether compared to the rest of the group (p =
      0.02), or to the reference data (p = 0.01). The U-NAG/Cr activity was higher in
      15 children without urolithiasis/nephrocalcinosis when compared to reference data
      (p < 0.01). There was no difference in U-Ca/24h between the children with and
      without urolithiasis/nephrocalcinosis (p = 0.58). These findings suggest that
      tubular impairment, as reflected by U-NAG/Cr, might occur in children with IH,
      especially in patients with urolithiasis/nephrocalcinosis. There doesn't seem to
      be a direct relationship between the U-NAG/Cr activity and the degree of calcium
      leakage.

PMID- 16956120
TI  - Comparison of effects of different antidotes on tabun-induced cognitive
      impairment in rats using water maze.
AB  - In the past, scientists focused on the development of antidotes (mainly
      anticholinergics in combination with reactivators of inhibited
      acetylcholinesterase-oximes) to increase the number of surviving nerve agent
      intoxicated individuals. Recently, they are interested in antidotes able not only
      to protect nerve agent-poisoned men from lethal toxic effects but also to improve
      their life quality by improvement of their central cognitive functions. In our
      study, the water maze was used to measure spatial working learning and memory in
      the case of tabun-induced cognitive impairment in albino Wistar rats. Antidotal
      treatment consisted of atropine alone or a combination of atropine with an oxime
      (obidoxime, trimedoxime or oxime HI-6). Our results suggest that atropine alone
      is not sufficient as a treatment for saving cognitive functions impaired by
      tabun. On the other hand, the addition of oxime to atropine contributes to
      improvement of cognitive performance in tabun-poisoned rats regardless of type of
      oxime.

PMID- 16956121
TI  - Monoclonal gammopathies in a series of 1743 plasma donors.
AB  - We carried out a retrospective analysis on a series of 1743 plasma donors during
      the period from January 1999 to February 2004 to determine the frequency of
      monoclonal gammopathies occurrence. In the whole group, we observed 0.68%
      occurence and in the subgroup of donors over 40 years of age even 1.18%
      occurrence of the serum paraprotein. We have presented our recommendations for
      the screening of monoclonal gammopathies in blood donors.

PMID- 16956122
TI  - Cytoskeletal changes in non-apoptotic cell death.
AB  - Dynamic morphology and cytoskeletal changes in Hep-2 cells exhibiting features of
      non-apoptotic cell death after treatment with zinc were studied using
      immunofluorescence microscopy and spectrofluorimetry. Among early morphological
      changes in treated cells was development of vacuolization, surface blebbing,
      relatively rapid cell detachment from substratum, cell shrinkage and, in some
      cases, appearance of membrane protrusions. Staining of microfilaments revealed
      rapid rearrangement and subsequent loss of F-actin accompanied by changes in the
      amount and localization of G-actin. The use of specific kinase and caspase
      inhibitors did not prevent surface blebbing as well as other morphological
      features in dying cells. Dying cells were only weakly positive for phosphatidyl
      serine and showed only a transient activation of caspase-9 with no signs of
      activation of caspase-3. These results suggest the existence of nonapoptotic cell
      death showing morphological features of both apoptosis and necrosis but,
      biochemically, resembling some other type of cell death.

PMID- 16956123
TI  - Posttraumatic pneumopericardium: a sign of severe injury or radiodiagnostic
      rarity?
AB  - We present three cases of pneumopericardium following blunt chest trauma injury.
      All three patients were victims of road traffic accidents. All had multiple
      associated injuries and pneumopericardium was found as the additional finding.
      Pneumopericardium was treated conservatively with thoracic drains placement and
      patients observation. Transesophageal echocardiography was used as a method of
      choice for exclusion of cardiac air tamponade. All three patients survived.

PMID- 16956124
TI  - Symmetry types, systems and their multiplicity in the structure of adenovirus
      capsid. II. Rotational facet groups of five-, three- and two-fold symmetry axes.
AB  - The icosahedral adenovirus capsid has three rotational symmetry axes of different
      types. The six five-fold, ten three-fold and the fifteen two-fold axes have two
      superficial points each, altogether 62. The axes determine the number and
      location of the identical rotational facet groups and that during the different
      rotational phases which other regular facets and with what multiplicity shall be
      covered by them. The number of rotational facets of the five-, three- and two
      fold rotational symmetry axes is 4, 6.66 and 10, respectively. In all the three
      cases, there are two kinds of possible arrangements of the facets. During the
      rotation--when the facets of the facet group placed on one by one to the
      neighbouring identical facet groups--at the five-fold axes, the facets of the
      rotational facet group get into cover position 12 times with all the 20 regular
      capsid facets, 20 times at the three-fold axes, and 30 times at the two-fold axes
      in a way that a different facet combination (facet hit) falls to every facet, and
      the original symmetry is not disturbed. After all, this means 240, 400 and 600
      facet combinations, i.e. multiplicity in case of five-, three- and two-fold
      symmetry axes respectively, and these numbers correspond with that of the
      theoretically possible variations. The same results can be calculated by
      multiplying the number of real rotations of the capsid bringing the body into
      itself, i.e. the number 60 with the number of facets contributing to the five-,
      three- and two-fold rotational phases. The other way of the determination of
      multiplicity takes into account that all the facet groups of the capsid rotate
      simultaneously during all the rotational phases, and this multiplies the number
      of multiplicity with the number of the rotational types five-, three- and two
      fold which result in one and the same multiplicity number in the case of five-,
      three- and two-fold symmetry, alike 1200. Perpendicular to the five-fold symmetry
      axes with the line of intersection drawn horizontally in the middle along the 6
      geodetic ribbon like motifs a regular decagonal intersection forms and the capsid
      can be cut into two equal parts, in which the polypeptides show a 72 degree
      rotation from each other, but with a proper rotation the polypeptides get into a
      congruent position, which means 300 or 600 specific facet combinations. The
      capsid similar to the icosahedron has also 15 virtual mirror planes which divide
      the capsid into two, identically arranged halves, forming six right angle
      triangles on each facet, altogether 120 smaller rectangular so-called Mobius
      triangles on the surface. In the three-fold symmetry axis of the facets, these
      triangles in two separate groups of three can be rotated symmetrically with 120
      degrees according to the orientation of the polypeptide subunits in a way that
      the hexon and other polypeptides too nearly cover each other. Consequently, the
      adenovirus capsid is a symmetrically arranged body in which several various
      symmetry types and symmetry systems can be found and their structural symmetry
      elements exist simultaneously and covering each other. The icosahedral symmetry
      types and systems are valid and functional simultaneously and in parallel with
      great multiplicity, but the existence of more than 1500 structural elements in
      several depth levels, their order of location and distribution make the symmetry
      of the capsid richer and more complex.

PMID- 16956125
TI  - Use of the BIOMIC Video System to evaluate the susceptibility of clinical yeast
      isolates to fluconazole and voriconazole by a disk diffusion method.
AB  - The ARTEMIS Global Antifungal Susceptibility Program provides the collection of
      epidemiological data and the results of the fluconazole and voriconazole
      susceptibility testing of yeast isolates. Participating in this study, a total of
      7318 clinical yeast isolates were tested from different geographical areas in
      Hungary in the period 2001 to 2003. The species isolated most frequently was C.
      albicans (68.8%), followed by C. glabrata (11.8%), C. tropicalis (5.7%) and C.
      krusei (4.6%). Isolates of C. albicans, C. kefyr, C. lusitaniae, C. tropicalis
      and C. parapsilosis were highly susceptible to fluconazole (78.9-100%). The rates
      of isolation of fluconazole-resistant C. glabrata and C. krusei were higher in
      our study than the global mean in 2001 (28.2% and 87.5% vs. 18.3% and 70.2%,
      respectively). Differences were detected in the distribution of fluconazole
      susceptibility data of C. glabrata isolates in the different counties of Hungary:
      most of the resistant isolates were observed in the eastern part of the country.

PMID- 16956126
TI  - Adenovirus subversion of immune surveillance, apoptotic and growth regulatory
      pathways: a model for tumorigenesis.
AB  - The adenovirus system provides a novel model for evaluating the roles of multiple
      factors involved in tumour progression. In common with other DNA tumour viruses,
      adenovirus employs a variety of strategies to evade immune surveillance and
      perturbs cellular apoptotic and growth regulatory pathways to ensure efficient
      replication of progeny virions. Such subversion of cellular networks is also
      found in tumour cells. The mechanism behind the avoidance of immune surveillance
      and the extent of cellular network interference achieved by adenovirus is still
      being uncovered and is predicted to have ramifications for the design of cancer
      therapeutics.

PMID- 16956127
TI  - Heterogeneity of non-serotypable Campylobacter jejuni isolates.
AB  - Several phenotypic and genotypic methods are currently used to identify subtypes
      of Campylobacter jejuni isolates. Of the phenotypic methods one, i.e. serotyping
      based on the heat stable antigen, is often hindered by the relatively large
      number of un-typable (NT) strains. Little is known, however, about the
      heterogeneity of the group formed by these NT strains. Therefore we serotyped 92
      Hungarian, non-outbreak C. jejuni isolates and subjected the 28 NT strains to
      molecular analysis using PCR-RFLP of the flaA gene and to pulsed-field gel
      electrophoresis. With both methods the NT strains were classified into several
      molecular types (17 and 25, respectively), while the number of subgroups based on
      the results of the two techniques combined was twenty-six. These results indicate
      that the NT group of strains is extremely heterogeneous in Hungary, and the
      epidemiological connection between two NT isolates cannot be established or
      excluded without the use of molecular typing techniques.

PMID- 16956128
TI  - The place of molecular genetic methods in the diagnostics of human pathogenic
      anaerobic bacteria. A minireview.
AB  - Anaerobic infections are common and can cause diseases associated with severe
      morbidity, but are easily overlooked in clinical settings. Both the relatively
      small number of infections due to exogenous anaerobes and the much larger number
      of infections involving anaerobic species that are originally members of the
      normal flora, may lead to a life-threatening situation unless appropriate
      treatment is instituted. Special laboratory procedures are needed for the
      isolation, identification and susceptibility testing of this diverse group of
      bacteria. Since many anaerobes grow more slowly than the facultative or aerobic
      bacteria, and particularly since clinical specimens yielding anaerobic bacteria
      commonly contain several organisms and often very complex mixtures of aerobic and
      anaerobic bacteria, considerable time may elapse before the laboratory is able to
      provide a final report. Species definition based on phenotypic features is often
      time-consuming and is not always easy to carry out. Molecular genetic methods may
      help in the everyday clinical microbiological practice in laboratories dealing
      with the diagnostics of anaerobic infections. Methods have been introduced for
      species diagnostics, such as 16S rRNA PCR-RFLP profile determination, which can
      help to distinguish species of Bacteroides, Prevotella, Actinomyces, etc. that
      are otherwise difficult to differentiate. The use of DNA-DNA hybridization and
      the sequencing of special regions of the 16S rRNA have revealed fundamental
      taxonomic changes among anaerobic bacteria. Some anaerobic bacteria are extremely
      slow growing or not cultivatable at all. To detect them in special infections
      involving flora changes due to oral malignancy or periodontitis, for instance, a
      PCR-based hybridization technique is used. Molecular methods have demonstrated
      the spread of specific resistance genes among the most important anaerobic
      bacteria, the members of the Bacteroides genus. Their detection and investigation
      of the IS elements involved in their expression may facilitate following of the
      spread of antibiotic resistance among anaerobic bacteria involved in infections
      and in the normal flora members. Molecular methods (a search for toxin genes and
      ribotyping) may promote a better understanding of the pathogenic features of some
      anaerobic infections, such as the nosocomial diarrhoea caused by C. difficile and
      its spread in the hospital environment and the community. The investigation of
      toxin production at a molecular level helps in the detection of new toxin types.
      This mini-review surveys some of the results obtained by our group and others
      using molecular genetic methods in anaerobic diagnostics.

PMID- 16956129
TI  - Enhancement of ethyl propionate synthesis by poly (AAc-co-HPMA-cl-MBAm)
      immobilized Pseudomonas aeruginosa MTCC-4713, exposed to Hg2+ and NH4+ ions.
AB  - A purified alkaline thermo-tolerant bacterial lipase from Pseudomonas aeruginosa
      MTCC-4713 was immobilized on a poly (AAc-co-HPMA-cl-MBAm) hydrogel. The hydrogel
      bound lipase achieved 93.6% esterification of ethanol and propionic acid (300 mM:
      100 mM) into ethyl propionate at temperature 65 degrees C in 3 h in the presence
      of a molecular sieve (3 angstroms). In contrast, hydrogel-immobilized lipase pre
      exposed to 5 mM of HgCl2 orNH4Cl resulted in approximately 97% conversion of
      reactants in 3 h into ethyl propionate under identical conditions. The salt
      exposed hydrogel was relatively more efficient in repetitive esterification than
      the hydrogel-bound lipase not exposed to any of the cations. Moreover, bound
      lipase exposed Hg2+ or NH4+ ions showed altered specificity towards p-nitrophenyl
      esters and was more hydrolytic towards higher C-chain p-nitrophenyl esters (p
      nitrophenyl laurate and p-nitrophenyl palmitate with C 12 and C 16 chain) than
      the immobilized lipase not exposed to any of the salts. The later showed greater
      specificity towards p-nitrophenyl caprylate (C 8).

PMID- 16956130
TI  - Disturbance of human immunohomeostasis by environmental pollution and alcohol
      consumption.
AB  - Environmental pollution and consumption of alcohol evoke various
      immunomodulations promoting the progress of different pathologies. The purpose of
      this study was to evaluate the influence of alcohol consumption intensity on the
      immune system functions of humans living in ecologically different regions, i.e.
      in a district polluted with industrial siftings (Trakai, n = 270) and in a
      relatively clean district (Sirvintos, n = 250). In the Trakai cohort 96% and in
      Sirvintos group 89% of persons consumed alcohol. With regard to alcohol
      consumption habits the immunohaematological indices were investigated in the
      following four groups: abstinents, light alcohol users, moderate alcohol users
      and alcohol abusers. We determined the compensatory mechanisms of immune system
      functions of moderate alcohol users and alcohol abusers in comparison with
      abstinents in the relatively clean Sirvintos district. In the Trakai district
      polluted with industrial siftings such compensatory reactions where not found.
      Thus, damage to the immune system functions is not only an endogenous risk factor
      for many diseases, but also an indicator of organism injury. This investigation
      stated, that immunity disturbance in humans depends on alcohol consumption
      intensity and place of residence.

PMID- 16956131
TI  - Enhanced thermostability of silica-immobilized lipase from Bacillus coagulans BTS
      3 and synthesis of ethyl propionate.
AB  - A lipase from the thermophilic isolate Bacillus coagulans BTS-3 was produced and
      purified. The enzyme was purified 40-fold to homogeneity by ammonium sulfate
      precipitation and DEAE-Sepharose column chromatography. Its molecular weight was
      31 kDa on SDS-PAGE. The purified lipase was immobilized on silica and its binding
      efficiency was found to be 60%. The enzyme took 60 min to bind maximally onto the
      support. The pH and temperature optima of immobilized lipase were same as those
      of the free enzyme, i.e. 8.5 and 55 degrees C, respectively. The immobilized
      enzyme had shown marked thermostability on the elevated temperatures of 55, 60,
      65 and 70 degrees C. The immobilized enzyme was reused for eigth cycles as it
      retained almost 80% of its activity. The catalytic activity of immobilized enzyme
      was enhanced in n-hexane and ethanol. The immobilized enzyme when used for
      esterification of ethanol and propionic acid showed 96% conversion in n-hexane in
      12 h at 55 degrees C.

PMID- 16956132
TI  - Rationing of medical care by age.

PMID- 16956133
TI  - A new direction for community-based health services.

PMID- 16956135
TI  - New faculty of forensic and legal medicine.

PMID- 16956134
TI  - Skin cancer: prevalence, prevention and treatment.

PMID- 16956136
TI  - Designer drugs: the biologic therapies.

PMID- 16956137
TI  - Therapeutic apheresis--plasmapheresis.

PMID- 16956138
TI  - Allergen immunotherapy (desensitisation) for allergic diseases.

PMID- 16956139
TI  - Oral immunosuppressive drugs.

PMID- 16956140
TI  - Current clinical uses of intravenous immunoglobulin.

PMID- 16956141
TI  - Professional standards in the USA: overview and new developments.
AB  - The USA and the UK are both experiencing dramatic changes in the management and
      regulation of physician practice. While the USA and the UK share a commitment to
      evidence-based medicine and maintain traditions in how medicine is practised, the
      healthcare delivery systems and the process and approaches to professional
      management in the two countries are quite different. This article describes the
      process of the initial certification of graduating medical trainees and the
      approach to maintenance of certification among practising physicians in the USA,
      with a focus on new developments in board certification and their link to
      healthcare quality and public accountability.

PMID- 16956142
TI  - Expanding community-based health services.
AB  - The recently published White Paper on developing community-based health services
      contains proposals which will have a direct impact on a number of hospital
      specialties and on the provision of primary and preventive care in the community.
      Many of these developments are to be welcomed, but a clearer understanding is
      required of the most appropriate balance between hospital and community services
      in the future, of the educational implications of changing patterns of care in
      the NHS and of the resource implications of these reforms.

PMID- 16956143
TI  - Assisted dying: a palliative care physician's view.
AB  - Lord Joffe's revised Assisted Dying for the Terminally III Bill was defeated in
      the House of Lords in May 2006, but it may return to Parliament in Autumn 2006.
      Assisted dying is being promoted as a logical extension to patient autonomy for
      those who are terminally ill and suffering intolerably, and proponents claim to
      have overwhelming public support. Those who have most experience of caring for
      the terminally ill, however, come out most strongly against any change in the
      current law. This paper suggests that estimates of public opinion are unreliable;
      that assisted dying is unnecessary if we are prepared to prioritise good end-of
      life care; and that a change in the law would do little to protect patients but
      would put other vulnerable members of society at risk.

PMID- 16956144
TI  - The portfolio: how was it for you? Views of F2 doctors from the Mersey Deanery
      Foundation Pilot.
AB  - A study was conducted between August 2004 and August 2005 to explore the
      experiences of Foundation year 2 (F2) trainees who used the learning portfolio on
      the Mersey Deanery pilot scheme. Seventy-three trainees (77%) reported receiving
      their portfolio during their induction. In their first four-month placement, 90
      trainees (96%) completed the two case-based discussions, 80 (87%) the three mini
      clinical examinations and 92 (97%) the two direct observation of practical
      procedures. The number of trainees who felt there was an opportunity to make a
      record of and analyse clinical critical incidents and critical incidents related
      to professional behaviour was only 32 (35%) and 13 (15%) respectively. Free text
      responses suggested that trainees appreciate the portfolio but that an
      understanding of its content and purpose, particularly by educational
      supervisors, is paramount to its success.

PMID- 16956145
TI  - Systematic review of systematic reviews of acupuncture published 1996-2005.
AB  - Systematic reviews of acupuncture have tended to support its use, but few applied
      rigorous inclusion criteria. We tested the credibility of conclusions of
      systematic reviews of acupuncture published since 1996 by applying rigorous
      inclusion criteria. Reinterpretation used randomised and double blind trials with
      valid outcomes or design, and with information available from at least four
      trials or from 200 patients. Qualified support for acupuncture was originally
      reported in 12 out of 35 systematic reviews, and strong support was found in
      another six. Applying stricter inclusion criteria, however, showed that none of
      the 35 reviews supported acupuncture, predominantly because there were too few
      patients in the randomised, double blind studies. Six reviews with more than 200
      patients in randomised, double blind studies had good evidence of no benefit.
      Systematic reviews of acupuncture have overstated effectiveness by including
      studies likely to be biased. They provide no robust evidence that acupuncture
      works for any indication.

PMID- 16956146
TI  - Spheres of medical influence: President, Royal College of Physicians.

PMID- 16956147
TI  - William Withering's legacy--for the good of the patient.
AB  - The lessons that the physician William Withering learned from his studies of
      digitalis are still relevant today. This paper highlights four of these lessons
      and updates them using the tools of clinical pharmacology and
      pharmacoepidemiology. First, Withering learned that failure to prepare digitalis
      from the foxglove in a standard manner resulted in a product with unpredictable
      clinical effects. Preparation of medicines from plants since then has not
      followed similar good practice and medicines have often not been granted
      marketing authorisation because of variability in their quality. Second,
      differences in the response to digitalis were noted by Withering, but he had
      little idea of their basis. Clinical pharmacology has shown that for drugs such
      as digitalis differences are caused by variability both in receptor sensitivity
      and in drug disposition. Third, the dose-response characteristics of digitalis
      were well known to Withering. Modern techniques of measuring response, such as
      the use of biomarkers, have made such studies easier, although clinical
      observations remain the gold standard. Fourth, Withering documented many of the
      adverse effects of digitalis. The use of various modern databases has facilitated
      the analysis of clinical toxicology and thus of risk-benefit profiles.

PMID- 16956148
TI  - Crossing the 'bright line'--difficult decisions at the end of life.
AB  - Patients tell us stories about their lives, their symptoms and their
      interpretation of them. As physicians we try to make sense of the stories,
      piecing together the fragments that come our way to discern a diagnosis which we
      then confirm or refute by examination and investigation. Thus was Samuel Gee's
      life as a physician: with little in the way of diagnostic tools his 'clinical
      skills' had to be honed finely and his diagnostic nose well attuned. Perhaps we
      have today lost some of that clinical intuition. We seek the evidence base for
      all we do, failing to observe subtleties in our quest for hard science. Following
      Gee's esteemed lead--for he was celebrated for his clinical descriptions--I will
      unashamedly use doctor-patient experiences to illustrate my points, particularly
      around end-of-life decisions.

PMID- 16956149
TI  - Mother and child care in art.

PMID- 16956150
TI  - Adults with LCH--orphans with an orphan disease.

PMID- 16956151
TI  - Non-consultant career grade doctors: past, present and future.

PMID- 16956153
TI  - Impact of specialist care on clinical outcomes for medical emergencies.

PMID- 16956152
TI  - A personal view of assisted dying.

PMID- 16956155
TI  - Clinical freedom, patient autonomy and NICE.

PMID- 16956154
TI  - Standardised early warning scoring system.

PMID- 16956156
TI  - Patterns and costs of treatment for heroin dependence over 12 months: findings
      from the Australian Treatment Outcome Study.
AB  - OBJECTIVE: To determine patterns and costs of treatment for heroin dependence
      over a 12-month period among a cohort of heroin users seeking treatment. METHODS:
      The design was a longitudinal cohort study of heroin users seeking treatment who
      participated in the Australian Treatment Outcome Study (ATOS), which was
      conducted in Sydney, Melbourne and Adelaide, Australia. Treatment for heroin
      dependence, for those who were followed up at 12 months, was recorded and costed.
      Unit costs, obtained from secondary sources, were used to estimate the cost of
      treatment. This study does not include wide societal costs and only includes
      personal costs as they pertain to treatment. RESULTS: A follow-up rate of 81% at
      12 months was achieved, resulting in data for 596 participants. Participants
      spent an average of 188 days in treatment over 2.7 episodes. Sixty-nine per cent
      of the sample reported at least one episode of treatment following their index
      treatment. There was a noticeable trend for subjects who received maintenance or
      residential rehabilitation as their index treatment to return to the same form of
      treatment for subsequent episodes. In contrast, those who received detoxification
      as index treatment accessed a wider variety of treatment types over the follow-up
      period. The cost of treatment over the 12-month follow-up totalled dollar
      3,901,416, with a mean of dollar 6,517 per person. CONCLUSIONS AND IMPLICATIONS:
      This study demonstrates that individuals seeking treatment have multiple
      treatment episodes throughout a 12-month period, with a tendency to return to the
      same form of treatment. This study also demonstrates that it is feasible and
      affordable to provide ongoing treatment for a group of heroin users seeking
      treatment.

PMID- 16956157
TI  - Asbestos-related disease from recycled hessian superphosphate bags in rural
      Western Australia.
AB  - OBJECTIVES: To describe the dissemination of asbestos fibres within the Western
      Australian community. METHODS: A case report. RESULTS: A 60-year-old female was
      referred for investigation of calcified pleural plaques. On questioning, she
      recalled exposure to asbestos as a child on the family farm. She had shaken
      hessian bags prior to recycling to the fertiliser supplier. Her father survived
      to 90 years. Her mother died from malignant pleural mesothelioma. Four of five
      siblings had shaken the bags, two had radiographic evidence of pleural plaques
      while two others had not had recent chest x-rays. CONCLUSIONS: It appears that
      the use of recycled hessian bags for the fertiliser industry was endemic in the
      State during the period 1943-66. It is possible that many farmers and their
      families have had similar exposure to asbestos. IMPLICATIONS: The risk of
      developing an asbestos-related disease is not restricted to any specific social
      or employment groups within the Australian community.

PMID- 16956158
TI  - Legislative and regulatory measures for preventing alcohol-related drownings and
      near-drownings.
AB  - OBJECTIVE: Alcohol contributes to about 30% of drowning fatalities associated
      with recreational aquatic activity and to 35% of drownings associated with
      boating. We consider regulatory and legislative strategies for preventing such
      deaths. METHODS: We contacted water police in each Australian State and Territory
      to identify legislation creating alcohol-related offences for operators of
      recreational boats in their jurisdiction and to determine whether they conducted
      random breath testing (RBT). We also sought information from all 152 (81 urban
      and 71 rural) local government councils in NSW regarding restrictions on
      consumption of alcohol in public places within their shires. RESULTS: Four
      Australian States (New South Wales, Queensland, Victoria and South Australia)
      have legislation prescribing maximum blood alcohol concentrations (BACs) for
      operators of recreational boats; all support this with RBT. Western Australia,
      Tasmania and the Australian Capital Territory define more general offences for
      operating vessels while under the influence of alcohol. Prohibitions or
      restrictions on consumption of alcohol in public places exist in 78 of the 86
      shires in NSW that responded: 69 councils had alcohol-free zones, 53 restricted
      consumption of alcohol in public parks and reserves, and 33 had prohibitions or
      restrictions in some aquatic environments. CONCLUSIONS/IMPLICATIONS: Legislation
      restricting BACs for recreational boat operators should be adopted in all
      Australian States and Territories. Optimal legislation would require that all
      occupants of recreational boats are required to comply with prescribed BAC
      levels, including when vessels are at anchor. Extension of by-laws prohibiting or
      restricting the consumption of alcohol specifically in aquatic environments
      warrants consideration.

PMID- 16956159
TI  - Tobacco and alcohol-related mortality in men: estimates from the Australian
      cohort of petroleum industry workers.
AB  - OBJECTIVE: To measure the association between major causes of mortality and
      tobacco use; and the association between major causes of mortality and alcohol
      use, after adjusting for tobacco use. METHOD: Employees of Australian Institute
      of Petroleum member companies were enrolled in the cohort in four industry-wide
      surveys between 1981 and 1999. Mortality of 16,547 men was determined up to 31
      December 2001 and cancer incidence to 31 December 2000. Relative mortality and
      cancer incidence rates were computed for smoking categories compared with never
      smokers, and for alcohol consumption compared with total abstainers. RESULTS: The
      highest category of smoking, more than 30 cigarettes per day, was associated with
      more than a threefold increase in all-cause mortality, a 60% increase in cancer
      incidence, a 43-fold increase in lung cancer incidence, and a more than fourfold
      increase in mortality from ischaemic heart disease. There were only four cancers
      in lifelong non-smokers. Moderate alcohol consumption provided a protective
      effect from death from all causes combined, relative to nil or low consumption,
      and relative to heavy alcohol consumption. The main contributor to the protective
      effect was protection against death from ischaemic heart disease. CONCLUSIONS:
      Lifelong avoidance of tobacco and moderate alcohol consumption confer significant
      improvements on life expectancy.

PMID- 16956160
TI  - Phased-in smoke-free workplace laws: reported impact on bar patronage and
      smoking, particularly among young adults in South Australia.
AB  - OBJECTIVES: To measure the reported impact of phased-in smoke-free bar laws on
      bar patronage and smoking behaviour, particularly among young adults. METHODS:
      Cross-sectional survey of a representative sample of 2,004 South Australian
      adults, conducted four months into Phase I of the new laws. A comparable survey
      was conducted in 2003. RESULTS: Awareness of and support for the smoke-free laws
      were high. Phase I of the new laws did not reduce patronage. Young adults (18-24
      years) reported higher patronage of bars and greater impact of the new laws on
      patronage, current smoking and future likelihood of quitting. CONCLUSIONS AND
      IMPLICATIONS: Smoke-free laws are an effective public health measure to protect
      against second-hand smoke. Evidence is now emerging that they may also reduce
      smoking among young people, as bars are social settings with potential to alter
      social norms about smoking and promote reduced consumption and quitting.

PMID- 16956161
TI  - Travel undertaken by women accessing private Victorian pregnancy termination
      services.
AB  - OBJECTIVE: To investigate the extent and cost of travel undertaken by women
      accessing Victorian termination of pregnancy services. DESIGN, SETTING AND
      PARTICIPANTS: This was a multi-centre, cross-sectional observational study of
      women receiving privately funded pregnancy termination services, conducted
      between November 2002 and June 2003 at eight major pregnancy termination service
      providers in Victoria. MAIN OUTCOME MEASURES: Distance travelled, money and time
      expended undertaking travel, and reasons women chose particular clinics. RESULTS:
      Of the 1,244 Australian resident respondents who resided in Victoria, 9.3%
      travelled more than 100 km to access services. Teenagers were 2.5 times more
      likely than other respondents to travel further than 100 kilometres (km) (18.2%
      compared with 7.8%, OR = 2.5, 95% CI 1.5-4.2, p < 0.001). Women originated from
      all Australian States and Territories except South Australia and 13.7% were from
      Statistical Divisions other than Melbourne. More than one-third of respondents
      (41.3%) chose their clinic because they were referred by a doctor or general
      practitioner. CONCLUSION: Many pregnancy termination patients face substantial
      and immediate costs beyond the service fee, as well as the difficulties
      associated with poor continuity of care and significant time away from home.
      Patients and service providers should be consulted further to determine
      appropriate clinical services, support services and subsidy schemes for the
      sizeable proportion of patients who undertake long-distance travel to access
      pregnancy termination services.

PMID- 16956162
TI  - A survey of New Zealand's Territorial Local Authorities' policies, plans and
      programs promoting physical activity.
AB  - OBJECTIVE: To investigate New Zealand's Territorial Local Authorities' (TLAs')
      policies and plans promoting physical activity. METHOD: Postal survey of senior
      planners in New Zealand's TLAs, undertaken 2004/05. RESULTS: Only 59% of
      respondents reported that their TLA had an overall plan or policy for physical
      activity promotion. Most reported policies and plans for open spaces (82%), parks
      (95%) and recreational facilities (89%). Those for pedestrian pathways were
      common (70%), but cycle lanes (56%) and shared use pathways (57%) were less so.
      Rural TLAs and those with more deprivation were less likely to have an overall
      policy (OR = 0.84, 95% CI 0.72-0.98) or direct involvement in promotion (OR =
      0.94, 95% CI 0.89-0.99). CONCLUSIONS: Considerable scope exists for New Zealand's
      TLAs, especially those that are largely rural, low growth and with greater
      deprivation, to promote physical activity. IMPLICATIONS: Physical activity policy
      development and planning should be given greater emphasis; those with more
      deprivation and isolation need additional resources to avoid increasing
      inequalities. Closer engagement between TLAs and population health agencies,
      transport and education sectors would accelerate progress. Policy monitoring,
      such as we have described, is one way of tracking such progress.

PMID- 16956163
TI  - Geographic representativeness for sentinel influenza surveillance: implications
      for routine surveillance and pandemic preparedness.
AB  - OBJECTIVE: To review the guidelines for geographic representativeness applied to
      sentinel influenza surveillance as proposed in the Framework for an Australian
      Influenza Pandemic Plan (1999). METHODS: The number of sentinel practices,
      participating general practitioners and their consultation rates per 100,000
      population, by region, were described for the Victorian sentinel surveillance
      system for 2003 and 2004. Influenza-like illness rates per 1,000 consultations
      were calculated for all participating practices and for a subset of regular
      participators. Indicators of seasonal influenza activity, set according to
      predefined thresholds, were compared in the two groups. RESULTS: During these two
      influenza seasons, a subset of approximately one-quarter (27%) of participating
      practices provided almost half (45%) of the patient swabs and detected the same
      level of influenza activity over two influenza seasons as all participating
      practices. However, this subset of GPs recorded only 0.3% of all GP consultations
      in Victoria in 2004. CONCLUSIONS: There should be an updated, evidence-based
      strategy for interpandemic influenza based on the number of general practice
      consultations. Requirements for surveillance during various pandemic phases also
      need to be reviewed.

PMID- 16956164
TI  - Do all ethnic groups in New Zealand exhibit socio-economic mortality gradients?
AB  - OBJECTIVES: First, to establish whether a deprivation gradient in all-cause
      mortality exists for all ethnic groups within New Zealand; second, if such
      gradients do exist, whether their absolute slopes are the same; and third, if
      such gradients exist, what impact the unequal deprivation distributions of the
      different ethnic groups have on the observed ethnic inequalities in life
      expectancy at birth. METHOD: Abridged lifetables for the period 1999-2003 were
      constructed using standard demographic methods for each of four ethnic groups
      (Asian, Pacific, Maori and European) by NZDep2001 quintile and sex. Gradients
      were estimated by fitting generalised linear models to the quintile-specific life
      expectancy estimates for each ethnic group (by sex). The contribution of
      variation in deprivation distributions to inter-ethnic inequalities in life
      expectancy was estimated by re-weighting the quintile-specific mortality rates
      for each ethnic group using weights derived from the European deprivation
      distribution and recalculating the lifetable. RESULTS: All four ethnic groups
      exhibit deprivation gradients in all-cause mortality (life expectancy). Maori
      show the steepest gradients, with slopes approximately 25% steeper than those of
      Europeans for both males and females. By contrast, gradients among Asian and
      Pacific peoples are shallower than those of their European counterparts.
      CONCLUSION: While socio-economic gradients in health exist among all ethnic
      groups, they are relatively shallow among Pacific and (especially) Asian peoples.
      For these ethnic groups, caution should be exercised in applying deprivation or
      other socio-economic measures as proxy indicators of need for health services.

PMID- 16956165
TI  - A privacy challenge to longitudinal study methods: patient-derived codes.
AB  - Recent changes to privacy legislation in Australia have resulted in more
      stringent requirements with respect to maintaining the confidentiality of patient
      health information. We describe a method employed to de-identify health
      information collected in a longitudinal study using codes. Using a patient
      derived code that did not change during the life of the study follow-up resulted
      in errors in a quarter of the follow-up surveys. This may introduce bias that
      could compromise the validity of the study. Alternative methods of coding may
      alleviate some of these issues. However, removal of some of the constraints
      imposed by interpretations of privacy legislation may be the best way forward.

PMID- 16956166
TI  - Attrition in longitudinal studies: who do you lose?
AB  - OBJECTIVE: To describe the risk factors for various types of attrition in three
      age cohorts of women in a longitudinal study and to discuss strategies to
      minimise attrition. METHODS: Analysis of survey data from the Australian
      Longitudinal Study on Women's Health, collected by mailed questionnaire. In 1996,
      the study recruited and surveyed a national random sample of 'younger' (18-23
      years, n = 14,247), 'mid-age' (45-50 years, n = 13,716), and 'older' women (70-75
      years, n = 12,432), and began a staggered cycle of mailed follow-up
      questionnaires: 1998 (mid-age), 1999 (older), 2000 (younger) and so on.
      Demographic, health and social risk factors for attrition were examined using
      multivariate analysis. RESULTS: Attrition at survey 2 was highest among younger
      women (32%), mainly because of participants not being contactable (21%), and
      lower among the older (16%) and mid-age women (10%). At survey 1, the survey 2
      non-respondents were more likely to report having less education, being born in a
      non-English-speaking country and being a current smoker, in all cohorts, and had
      poorer health (mid-age and older cohort) and more difficulty managing on their
      income (younger and mid-age). CONCLUSION: Although the magnitude of different
      types of attrition was found to differ by age, there were several risk factors
      for attrition that remained consistent. These findings are important to inform
      future studies on ways to lessen or prevent systematic loss of participants.
      IMPLICATIONS: Recruitment and follow-up methods in longitudinal studies should be
      tailored to maximise retention of participants at higher risk of dropout.

PMID- 16956167
TI  - Evaluation of the implementation of the folate-neural tube defect health claim
      and its impact on the availability of folate-fortified food in Australia.
AB  - OBJECTIVE: To evaluate the implementation of the folate-neural tube defect (NTD)
      health claim and its impact on the availability of folate-fortified food in
      Australia. METHODS: During late 2005, a survey was conducted in 16 supermarkets
      across all Australian capital cities to identify the use of the folate-NTD health
      claim on the labels of the 128 food products listed in food standard 1.1A.2:
      'Transitional standard--Health claims' and the number of products fortified with
      folic acid. RESULTS: Seventy-nine per cent of existing listed food products were
      found and two of these were implementing the folate-NTD health claim. Forty-four
      per cent of these listed products, previously fortified with folic acid, were no
      longer fortified. One hundred and seventeen generally available food products
      were fortified with folic acid, predominantly breakfast cereals (73%). Twenty
      seven per cent of these folate-fortified products were listed in the transitional
      standard. CONCLUSIONS: The health claim was not used widely to inform women of
      child-bearing age of the importance of periconceptional folate intake. The
      increased availability of folate-fortified products generally has occurred
      independently of the health claim. Deficiencies in the verification system of the
      tested regulatory framework are identified. The voluntary regulatory provisions
      for both folate fortification and the use of the health claim diminished the
      States' influence over their implementation of public health tools.

PMID- 16956168
TI  - Assessment of the potential effect of incremental increases in folic acid intake
      on neural tube defects in Australia and New Zealand.
AB  - OBJECTIVE: To estimate the number of neural tube defects that could be prevented
      in Australia and New Zealand by increasing levels of folic acid intake. METHODS:
      Available data on prevalence of neural tube defects in Australia and New Zealand,
      folic acid supplement use and serum folate were used in a published model to
      estimate the number of neural tube defects that could be prevented in Australia
      and New Zealand for increments of folic acid intake from 0.1 mg daily to 1 mg
      daily. RESULTS: An increase of 0.2 mg folic acid per day was estimated to result
      in the prevention of 49 (95% CI 27-84) neural tube defects per year in Australia
      and 11 (95% CI 6-18) in New Zealand. A separate estimation for Indigenous
      Australians found that 0.2 mg of folic acid daily could prevent 7 (95% CI 4-11)
      neural tube defects in Indigenous infants per year. CONCLUSIONS: These data
      should be useful in considering primary preventive strategies for neural tube
      defects, including the possible introduction of mandatory fortification of food
      with folic acid. The estimates are imprecise because of limitations in the data
      used in the model. IMPLICATIONS: More representative and precise data on neural
      tube defects, serum folate levels and use of folic acid supplements from all
      Australian States and New Zealand are needed to refine the output from the model
      and to provide a baseline assessment of folate status against which to measure
      the effects of any future interventions to prevent neural tube defects.

PMID- 16956169
TI  - The Queensland Cancer Risk Study: behavioural risk factor results.
AB  - OBJECTIVE: To describe the population prevalence of key cancer risk behaviours in
      Queensland. METHODS: The Queensland Cancer Risk Study was a population-based
      survey of 9,419 Queensland residents aged 20-75 years. Information was collected
      through an anonymous, computer-assisted telephone interview between February and
      November 2004. Outcome measures included tobacco smoking, alcohol consumption,
      sun-tanning and sunburn, obesity, physical inactivity and poor diet, weighted by
      age, gender and geographic region. RESULTS: Prevalence of current smoking was
      25.2% for males and 20.8% for females and was highest in the 20-39 year age group
      and in rural/remote areas. Two-thirds of participants regularly drank alcohol; of
      these, 63% consumed excessive amounts of alcohol. Excessive sun exposure is still
      a problem; 70% of Queenslanders reported an episode of sunburn and 12% reported
      attempting to get a suntan in the past year. More than half of the respondents
      (53.9%) were above the healthy weight range, and 17.1% of males and 18.4% of
      females were obese. Just over 40% of Queensland adults reported having
      insufficient levels of physical activity. Fewer than half of the participants met
      recommended levels of fruit or vegetable consumption. CONCLUSIONS AND
      IMPLICATIONS: The majority of Queensland adults exhibit known, modifiable cancer
      risk behaviours. These results suggest that continuing efforts to reduce the
      prevalence of these risk factors are warranted. Specifically, significant gains
      could be made by targeting behaviour change programs at younger Queenslanders
      (aged 20-39 years), men, and those living in remote/ very remote areas of
      Queensland.

PMID- 16956170
TI  - Impact on callers to a men's domestic violence helpline.

PMID- 16956171
TI  - Indigenous health research--changes in 60 years.

PMID- 16956172
TI  - Breast is no longer best: the World Health Organization, the Multi-centre Growth
      Reference Study and normal infant feeding.

PMID- 16956173
TI  - Racism and healthcare: experiences of Arabic-speaking patients.

PMID- 16956174
TI  - [Forensic psychiatry in Flanders at a crossroad?].

PMID- 16956175
TI  - [Psychiatry and literature].
AB  - Among the books published in 2003 by the publishing house Van Oorschot in
      Amsterdam were 'Twee Ambachten', a collection of essays by Rutger Kopland and
      'Strikt', a novel by Minke Douwesz. The authors of both books are psychiatrists.
      Kopland has already made a name for himself as a writer, but Douwesz is a
      completely new name in Dutch literature. In this essay, which was inspired by the
      two books in question, I attempt to explore the relationship between psychiatry
      and literature. There are interfaces between psychiatry and literature, that
      because of very different reasons can be worth to be researched.

PMID- 16956176
TI  - [Towards a familiar-sounding paradigm and an example of a model for psychiatry. A
      conceptual addition to the profile outline of psychiatry].
AB  - The profile of the psychiatrist is being affected by all kinds of developments
      that are occurring in psychiatry and in many other fields and disciplines. The
      latest profile depicts the psychiatrist primarily as a medical specialist. The
      biopsychosocial model has been discarded following a round of brief and confusing
      criticism and the focus is now on intentional brain functions. However, the
      latter is not completely in focus and the interpretation is ambiguous. On closer
      consideration we find it impossible to continue supporting the biopsychosocial
      model. Nevertheless, it can still serve us well as a broad-basedfamiliar-sounding
      paradigm. We describe a model that fits into this paradigm.

PMID- 16956177
TI  - [Suicidal tendencies, a disorder that crosses boundaries between disciplines].
AB  - BACKGROUND: Suicidality is considered to be a facultative symptom of certain
      psychiatric disorders. AIM: To provide evidence in support of the view that
      suicidality is not only a symptom of other disorders or comorbid with them but is
      often a disorder in its own right. METHOD: We conducted a review of the
      literature. RESULTS: Suicidality manifests itself as a disorder in its own right
      without any one-to-one relationships with other psychiatric or somatic disorders
      or illnesses. CONCLUSION: Suicidality has specific features of its own such as
      susceptibility to interindividual contagion. By preventing suicide we may be able
      to forestall the development of other types of ill-health and thus improve the
      quality of the life that has been saved.

PMID- 16956178
TI  - [Reaction to 'About the comparison of public-private cooperation. Comment on
      Vandereycken'].

PMID- 16956179
TI  - [Reaction to 'Recent findings regarding the treatment of late-onset depression
      with vascular brain lesions'].

PMID- 16956180
TI  - Bronsted acid catalyzed addition of phenols, carboxylic acids, and tosylamides to
      simple olefins.
AB  - Intermolecular addition of phenols, carboxylic acids, and protected amines to
      inert olefins can be catalyzed by low concentrations (1-5%) of triflic acid.
      Functional groups, such as the methoxyl substitution on aromatics, could be
      tolerated if the concentration of triflic acid and the reaction temperature are
      controlled appropriately. This reaction provides one of the simplest olefin
      addition methods and is an alternative to metal-catalyzed reactions.

PMID- 16956181
TI  - Hydroamination and hydroalkoxylation catalyzed by triflic acid. Parallels to
      reactions initiated with metal triflates.
AB  - Intermolecular additions of the O-H bonds of phenols and alcohols and the N-H
      bonds of sulfonamides and benzamide to olefins catalyzed by 1 mol % of triflic
      acid and studies to define the relationship between these reactions and those
      catalyzed by metal triflates are reported. Cyclization of an alcohol containing
      pendant monosubstituted and trisubstituted olefins catalyzed by either triflic
      acid or metal triflates form products from addition to the more substituted
      olefin, and additions of tosylamide catalyzed by triflic acid or metal triflates
      form indistinguishable ratios of the two N-alkyl sulfonamides.

PMID- 16956182
TI  - Application of palladium-catalyzed allylic arylation to the synthesis of a (+/-)
      7-deoxypancratistatin analogue.
AB  - Palladium-catalyzed coupling of an aryl siloxane and an allylic carbonate
      proceeded in good yield to give an adduct that was converted to an analogue of
      (+/-)-7-deoxypancratistatin.

PMID- 16956183
TI  - Lithiation directed by amino alkoxides. Application to the synthesis of new
      disubstituted dihydrodipyridopyrazines.
AB  - The synthesis of new 4,6-disubstituted dihydrodipyridopyrazines starting from
      corresponding carboxaldehydes via lithiation directed by alpha-amino alkoxides is
      described. The N,N,N'-trimethylethylenediamine was used as amine component for in
      situ formation of the alpha-amino alkoxides. After optimization, this reaction
      allowed easy access to new interesting starting materials for further
      applications by palladium-catalyzed reactions.

PMID- 16956184
TI  - Perylene-3,4:9,10-tetracarboxylic acid bisimide dye as an artificial DNA base
      surrogate.
AB  - A phosphoramidite of the perylene bisimide dye was synthesized as a DNA building
      block that allows incorporation of this chromophore as an artificial nucleoside
      surrogate either at the 5'-terminus or at internal positions of duplex DNA. The
      internally incorporated perylene bisimide chromophore shows strong interactions
      with the DNA base stack; the 5'-terminally attached perylene bisimide is able to
      induce dimerization of two whole DNA duplexes.

PMID- 16956185
TI  - Asymmetric Morita-Baylis-Hillman reaction catalyzed by isophoronediamine-derived
      bis(thio)urea organocatalysts.
AB  - New and improved bis(thio)urea catalysts were synthesized from isophoronediamine
      (IPDA) and tested in the Morita-Baylis-Hillman reaction. The best results were
      achieved in the reaction of 2-cyclohexen-1-one with cyclohexanecarbaldehyde,
      using the catalyst depicted above, in combination with a novel base (N,N,N',N'
      tetramethylisophoronediamine, TMIPDA) in toluene. The desired Morita-Baylis
      Hillman product was obtained in 75% yield and 96% ee.

PMID- 16956186
TI  - Stable helical beta 3-peptides in water via covalent bridging of side chains.
AB  - An on-bead cyclization protocol of beta 3-peptides was developed, providing easy
      access to cyclic beta 3-peptides. With this methodology, a small library of
      helical cyclic beta 3-peptides was synthesized and investigated with CD
      spectroscopy. Covalent bridging of two side chains in beta 3-peptides
      significantly stabilized their helical conformation in aqueous solutions and
      turned out to be superior to the previously described electrostatic interactions.

PMID- 16956187
TI  - Synthesis of 2-vinylic indoles and derivatives via a Pd-catalyzed tandem coupling
      reaction.
AB  - A novel one-step synthesis of valuable 2-vinylic indoles and their tricycle
      derivatives is described. This reaction, which utilizes a gem-dibromovinyl unit
      as a readily available starting material, occurs via an efficient Pd-catalyzed
      tandem Buchwald-Hartwig/Heck reaction.

PMID- 16956188
TI  - Solid-state photolysis of alpha-azidoacetophenones.
AB  - Solid-state photolysis of 1 yields 2 in a crystal-to-crystal reaction. The
      reaction takes place by alpha-cleavage to form a benzoyl and an azido alkyl
      radical pair. The azido alkyl radicals rearrange into iminyl radicals and N2. The
      iminyl and benzoyl radicals are held in close proximity within the crystal
      lattice, which allows them to combine and form 2. X-ray structure analysis,
      molecular modeling and trapping studies support this mechanism.

PMID- 16956189
TI  - A dibenzofuran-based host material for blue electrophosphorescence.
AB  - Dibenzofuran (DBF) is converted to a vacuum-sublimable, electron-transporting
      host material via 2,8-substitution with diphenylphosphine oxide moieties. Close
      pi-pi stacking and the inductive influence of P=O moieties impart favorable
      electron-transport properties without lowering the triplet energy. A maximum
      external quantum efficiency of 10.1% and luminance power efficiency of 25.9 lm/W
      are realized using this material as the host for the blue-green
      electrophosphorescent molecule, iridium(III) bis(4,6-(di-fluorophenyl)pyridinato
      N,C(2')picolinate (FIrpic).

PMID- 16956190
TI  - Synthesis of Anti-beta-substituted gamma,delta-unsaturated amino acids via
      Eschenmoser-Claisen rearrangement.
AB  - Anti-beta-substituted gamma,delta-unsaturated amino acids have been synthesized
      via a novel design of the Eschenmoser-Claisen rearrangement. The rearrangement
      gives good isolated yields and excellent diastereoselectivity due to (Z)-N,O
      ketene acetal formation and the pseudochairlike conformations of the reaction
      intermediates. Upon reductive hydrolysis, important novel amino acids and amino
      alcohols were synthesized for the first time via this methodology.

PMID- 16956191
TI  - Achieving high selectivity and facile displacement with a new thiol auxiliary for
      boron-mediated aldol reactions.
AB  - Synthesis of a new thiol auxiliary (1) is readily achieved (in five or six steps,
      >74% overall yield from norephedrine) and is shown to give high
      diastereoselectivity in boron-mediated anti-aldol reactions with a range of
      aldehydes. This new thiol auxiliary may be directly displaced by a range of
      nucleophiles under very mild conditions, to give the corresponding phosphonate
      esters, alcohols, acids, SNAC thiolesters, and methyl esters.

PMID- 16956192
TI  - Synthesis of the C29-C37 bicyclic ether core of (+)-sorangicin A.
AB  - Construction of the unique bicyclic bis-ether core of the macrolide (+)
      sorangicin A has been achieved. This fragment was prepared by utilizing a one-pot
      cascade of three bond forming events. An epoxide opening of the epoxy tosylate 2
      led to the formation of the tetrahydropyran and subsequently to a second epoxide.
      Finally, a second epoxide opening closed the tetrahydrofuran ring. The bicyclic
      fragment was synthesized in just nine steps from (E)-cinnamaldehyde.

PMID- 16956193
TI  - Sequential kinetic resolution catalyzed by halohydrin dehalogenase.
AB  - A sequential kinetic resolution catalyzed by halohydrin dehalogenase was employed
      for the synthesis of two valuable enantiopure building blocks. Resolution of
      methyl 4-chloro-3-hydroxybutanoate methylester ((R,S)-2) with use of a Trp249Phe
      mutant of halohydrin dehalogenase yielded methyl 4-cyano-3-hydroxybutanoate
      methylester ((S)-4) with 96.8% ee (40% yield) and (S)-2 with 95.2% ee (41%
      yield). This reaction is carried out in aqueous solution under mild conditions
      and provides access to a useful statin side-chain building block.

PMID- 16956194
TI  - Development of an approach to the synthesis of the ABC ring system of
      Hemibrevetoxin B.
AB  - An efficient approach for the synthesis of a model of the ABC ring system of
      Hemibrevetoxin B is described. Key features include a ring expansion to yield the
      ring C oxepane, the reduction of a 2-furyl ketone with high levels of 1,3
      stereocontrol, and an Achmatowicz oxidative ring expansion to yield the ring A
      tetrahydropyran. All seven stereogenic centers present in the model compound were
      controlled with high levels (>98:<2) of diastereoselectivity.

PMID- 16956195
TI  - Agesamides A and B, bromopyrrole alkaloids from sponge Agelas species:
      application of DOSY for chemical screening of new metabolites.
AB  - Diffusion-ordered NMR spectroscopy (DOSY) is a versatile and powerful NMR
      technique and a noninvasive analytical method for mixture analysis that does not
      require prior physical separation of the analytes. In our search for new
      metabolites from natural resources, DOSY was applied for constituent analysis of
      crude bromopyrrole fractions separated from an Okinawan marine sponge Agelas sp.
      so that two new bromopyrrole alkaloids, agesamides A (1) and B (2), have been
      isolated. The structures and relative stereochemistry of 1 and 2 were elucidated
      from spectroscopic data.

PMID- 16956196
TI  - Synthesis, structure, and optical and electrochemical properties of star-shaped
      porphyrin-triarylamine conjugates.
AB  - A series of novel star-shaped porphyrin-triarylamine conjugates were synthesized
      by palladium-catalyzed cross-coupling reactions. The spectroscopic and
      electrochemical studies show that pi-conjugation of the porphyrin core is
      extended to the triarylamine moieties.

PMID- 16956197
TI  - An unsymmetrical approach to the synthesis of bismethylene triphosphate
      analogues.
AB  - A protected, unsymmetrical bismethylene triphosphate analogue was prepared by
      sequential Michaelis-Arbuzov reactions on ethyl bis(halomethyl)phosphinates. This
      species was monodeprotected at one of the terminal phosphonate groups in high
      yield. The resulting monodeprotected compound was used to achieve the first
      syntheses of the bismethylene triphosphate analogues of UTP and CTP.

PMID- 16956198
TI  - Synthesis of spiro[4.5]decane CF-ring analogues of 1 alpha,25-dihydroxyvitamin
      D3.
AB  - A novel series of analogues of calcitriol (1) is developed featuring a
      spirocyclic central core resulting from C18/C21-connection and C15/C16-deletion
      (2a, 2b). The synthesis of the key intermediate involves an Eschenmoser
      rearrangement of an enantiomerically pure bromo-substituted cyclohexenol.

PMID- 16956199
TI  - Preparation of a psammaplysene-based library.
AB  - A 28-member focused library, based on the pseudosymmetric template of the marine
      alkaloids psammaplysenes, was prepared from combinations of components that were,
      in turn, derived from 4-iodophenol.

PMID- 16956200
TI  - Carotenoid radical anions and their protonated derivatives.
AB  - In this study, we report the protonation reactions for astaxanthin and
      canthaxanthin radical anions in methanol, alkaline methanol, and aqueous 2%
      Triton X-100 at different pH values. The pKa values for the corresponding alpha
      hydroxy radical derivatives of astaxanthin, canthaxanthin, and beta-apo-8'
      carotenal were estimated in 2% Triton X-100. Also, the effects of the
      microenvironment and the structure of the carotenoids on the protonation rate
      constant are discussed.

PMID- 16956201
TI  - Novel 3D coordination palladium-network complex: a recyclable catalyst for Suzuki
      Miyaura reaction.
AB  - A novel solid-phase 3D metal-organic coordination network catalyst was prepared
      via self-assembly from PdCl2(CH3CN)2 and a trisphosphine hub with three flexible
      alkyl-chain linkers. This insoluble network complex efficiently catalyzed the
      Suzuki-Miyaura reaction under atmospheric conditions in water. This catalyst was
      reused without loss of catalytic activity.

PMID- 16956202
TI  - Synthesis and fluorescent properties of a new class of heterocycles of isoindole
      fused imidazoles with phenolic subunits.
AB  - A new class of heterocycles of isoindole fused imidazoles with phenolic subunits
      has been readily synthesized by a two-step one-pot reaction. In aprotic solvent
      they show high fluorescent properties (Phi(F) up to 0.93), but in protic polar
      solvent fluorescent intensity decreases. They show green fluorescence in weak
      acidic medium such as acetic acid but lack emission in basic medium. The
      compounds can also stain human squamous epithelium cells.

PMID- 16956203
TI  - Stereoselective functionalization of the 1'-position of 4'-thionucleosides.
AB  - Stereoselective synthesis of novel 1'-alpha-substituted-4'-thionucleosides was
      achieved starting from D-gulonic acid gamma-lactone via stereoselective
      nucleophilic substitution.

PMID- 16956204
TI  - Synthesis and light-emitting properties of bipolar oligofluorenes containing
      triarylamine and 1,2,4-triazole moieties.
AB  - A facile approach for synthesis of bipolar oligofluorenes, TAZ-OF(n)-NPh, n = 2
      or 3 end-capped with hole-transporting diphenylamino and electron-transporting
      triazole moieties by Suzuki cross-coupling as the key reaction has been
      developed. This novel bipolar oligofluorenes exhibited blue-emission, high
      thermal and morphological stabilities. The single-layer OLED based on TAZ-OF(2)
      NPh exhibited superior device performance with a maximum luminance of 1128 cd m(
      2) and luminance efficiency of up to 0.83 cd A(-1).

PMID- 16956205
TI  - Encapsulation of small molecules by a cavitand porphyrin self-assembled via
      quadruple hydrogen bonds.
AB  - A new and stable quadruple hydrogen-bonded capsule, tetracarboxylcavitand.meso
      tetra(2-pyridyl)porphyrin (1 x 2) has been synthesized and spectroscopically
      characterized. 1 x 2 can encapsulate small molecules of various size from methane
      to cyclopentane. The guest and host exchange rates were evaluated by EXSY.

PMID- 16956206
TI  - One-pot synthesis of N-substituted diaza[12]annulenes.
AB  - N-Substituted diaza[12]annulenes are obtained by one -pot reaction of N-(2,4
      dinitrophenyl)pyridinium chloride with amines in moderate to high yields. The 1H
      NMR spectrum reveals that diamagnetic ring current is generated in the
      diaza[12]annulene ring. The N-substituted diaza[12]annulenes are
      electrochemically active in solution.

PMID- 16956207
TI  - Phosphine-catalyzed alpha-P-addition on activated alkynes: A new route to P-C-P
      backbones.
AB  - n-Tributylphosphine was found to efficiently catalyze the alpha-P addition of H
      phosphonates, H-phosphinates, and H-phosphine oxide pronucleophiles on alkynes
      bearing phosphane oxide activating moieties. The reaction leads to 2-aryl-1-vinyl
      1,1-diphosphane dioxide derivatives in good yields affording a new route to P-C-P
      backbones. The products of this reaction are easily converted to biologically
      important 1,1-bis-phosphonates analogues.

PMID- 16956208
TI  - Large rigid blue-emitting pi-conjugated stilbenoid-based dendrimers: Synthesis
      and properties.
AB  - Two large pi-conjugated dendrimers (G0 and G1) employing the stilbenoid moiety as
      the bridge unit have been developed through the Suzuki and the Horner-Wadsworth
      Emmons reactions. The molecular weight of G1 is 10 973 Da. Both G0 and G1 have
      good fluorescence quantum yields and exhibit similar absorption and emission
      behaviors in solutions and in thin films. They emit strong blue fluorescence in
      films under the irradiation of UV light.

PMID- 16956209
TI  - Tetrabromo hydrogenated cardanol: Efficient and renewable brominating agent.
AB  - 2,4,4,6-Tetrabromo-3-n-pentadecyl-2,5-cyclohexadienone (TBPCO) has been
      synthesized and used as a new efficient, convenient, and environmentally friendly
      brominating agent.

PMID- 16956210
TI  - Anomalous anthracene arrangement and rare excimer emission in the solid state:
      transcription and translation of molecular information.
AB  - A novel molecular arrangement of anthracene moieties and the corresponding rare
      solid-state excimer emission is obtained by utilization of a ternary system. The
      system consists of ammonium anthracene disulfonate and adducts, and shows the
      modulation of the solid-state emission mode depending on the adducts. The adducts
      act as molecular information sources that are transcribed to the arrangement, and
      the arrangement is translated into the emission mode. This series of processes
      might be mimicry of central dogma.

PMID- 16956211
TI  - Understanding the origins of remote asymmetric induction in the boron aldol
      reactions of beta-alkoxy methyl ketones.
AB  - We report theoretical studies into the remote 1,5-stereoinduction shown by
      certain types of beta-alkoxy methyl ketones in boron-mediated aldol reactions
      with achiral aldehydes. For a range of common alkoxy groups, our calculations are
      in excellent agreement with experimentally observed diastereoselectivities. In
      the aldol transition structures, a stabilizing hydrogen bond between the alkoxy
      oxygen and formyl proton leads to preferential formation of the 1,5-adduct, by
      minimizing steric interactions between the beta-alkyl group and one of the
      ligands on boron.

PMID- 16956212
TI  - Efficient synthesis of N-prenylpyrroloindoline and N-prenylindole alkaloids based
      on a new four-reaction anionic domino process.
AB  - Treatment of 2,5-diketopiperazines or carbamates derived from tryptophan or
      tryptamine with iodomethyltrimethylsilane followed by lithium
      hexamethyldisilazane and a prenyl halide produced stereoselectively derivatives
      of the hexahydropyrrolo[2,3-b]indole system bearing prenyl substituents both at C
      3a and at the indoline nitrogen in a one-pot procedure involving a novel four
      reaction anionic domino process. The reaction was applied to the preparation of N
      prenyltryprostatin B and to achieving a very efficient formal total synthesis of
      the biologically active marine natural product (+/-)-debromoflustramine B.

PMID- 16956213
TI  - Selective substituent transfer from mixed zinc reagents in Ni-catalyzed anhydride
      alkylation.
AB  - The use of mixed zinc reagents in Ni-catalyzed anhydride alkylation results in
      preferential transfer of substituents (Ph > Me > Et >> iPr approximately TMSCH2)
      for the ligands bipy, dppe, and iPrPHOX. Utilization of such mixed species allows
      the use of 0.55 equiv of the diorganozinc reagent, effectively transferring both
      desired substituents when used in conjunction with a suitable second zinc
      reagent.

PMID- 16956214
TI  - Enantioselective conjugate radical addition to alpha'-hydroxy enones.
AB  - Enantioselective conjugate radical addition to alpha'-hydroxy alpha,beta
      unsaturated ketones, compounds containing bidentate donors, has been
      investigated. It has been found that radical additions to alpha'-hydroxy
      alpha,beta-unsaturated ketones in the presence of Mg(NTf2)2 and bisoxazoline
      ligand 5a proceeded cleanly, yielding the addition products in high chemical
      yields and good enantiomeric excesses.

PMID- 16956215
TI  - Herrmann-Beller phosphapalladacycle-catalyzed addition of alkynes to
      norbornadienes.
AB  - Herrmann-Beller (H-B) phosphapalladacycle selectively catalyzed the addition of
      terminal alkynes across one double bond of norbornadiene to afford exo-5-alkynyl
      bicyclo[2.2.1]hept-2-enes. The reaction shows general applicability to various
      functionalized alkynes and bicyclo[2.2.1]hepta-2,5-dienes. Insights into the
      mechanism of this reaction are discussed.

PMID- 16956216
TI  - Diastereoselective synthesis of beta-Aryl-C-nucleosides from 1,2-anhydrosugars.
AB  - The cis opening of glycal epoxides with arylaluminum reagents provides strict
      stereocontrol in C-glycosylation. beta-Aryl-C-2-deoxynucleosides are obtained
      from known glycals by an epoxidation-glycosylation-deoxygenation sequence.

PMID- 16956217
TI  - New three-step domino reaction, "thiophilic addition-beta-elimination of fluoride
      [3,3] sigmatropic rearrangement": Synthesis of alpha-allylic and alpha,alpha
      bis(allylic) alpha-trifluoromethyl dithioesters.
AB  - The three-step domino reaction, "thiophilic addition of an organomagnesium
      reagent onto dithioester-beta-elimination of fluoride-[3,3] sigmatropic
      rearrangement", provides the product of formal regiospecific substitution of a
      fluorine atom by an allyl group. This mild and versatile methodology was applied
      to the synthesis of various alpha-allylic and alpha,alpha-bis(allylic) alpha
      trifluoromethyl dithioesters.

PMID- 16956218
TI  - Synthesis of a beta-(1-->3)-D-rhamnotetraose by a one-pot, multiple radical
      fragmentation.
AB  - A naturally occurring beta-(1-->3)-D-rhamnotetraose has been constructed under
      conditions of sequential beta-selective mannosylation controlled by the 4,6-O-[1
      cyano-2-(2-iodophenyl)-ethylidene] protecting group. The route is concise,
      proceeding through a late-stage radical deoxygenation that successfully uncovers
      all four deoxy subunits at once.

PMID- 16956220
TI  - Cleavage of activated cyclic amines: Unprecedented approach toward 2-substituted
      cyclobutanones.
AB  - We report, for the first time, ring opening of activated four- to six-membered
      cyclic amines followed by an intramolecular expansion of cyclopropanol to
      cyclobutanone via carbocation intermediate. In the case of a N-tosylaziridine
      ester, a cyclobutanol was formed in a stereospecific manner during the
      Kulinkovich reaction step.

PMID- 16956219
TI  - Palladium-catalyzed, copper(I)-mediated coupling of boronic acids and
      benzylthiocyanate. A cyanide-free cyanation of boronic acids.
AB  - A new method for the synthesis of nitriles is described. As a complement to the
      classic cyanation of aryl halides using cyanide sources and a transition metal
      catalyst, the palladium-catalyzed cross-coupling of thiocyanates with boronic
      acids in the presence of copper(I) thiophene-2-carboxylate (CuTC) affords
      nitriles in good to excellent yields.

PMID- 16956221
TI  - A stereoselective synthesis of digitoxin and digitoxigen mono- and
      bisdigitoxoside from digitoxigenin via a palladium-catalyzed glycosylation.
AB  - A convergent and stereocontrolled route to trisaccharide natural product
      digitoxin has been developed. The route is amenable to the preparation of both
      the digitoxigen mono- and bisdigitoxoside. This route featured the iterative
      application of the palladium-catalyzed glycosylation reaction, reductive 1,3
      transposition, diastereoselective dihydroxylation, and regioselective protection.
      The natural product digitoxin was fashioned in 15 steps starting from
      digitoxigenin 2 and pyranone 8a or 18 steps from achiral acylfuran.

PMID- 16956222
TI  - Triazatriangulenium cations: Highly stable carbocations for phase-transfer
      catalysis.
AB  - Highly stable triazatriangulenium carbocations, of pK(R+) higher than 20, can be
      used as novel phase-transfer catalysts for several classical organic reactions,
      their intrinsic stability in strongly basic and nucleophilic conditions rendering
      this novel use feasible.

PMID- 16956223
TI  - Lewis acid mediated regioselective ring opening of benzylglycidol with dibenzyl
      phosphate: Short and attractive synthesis of dihydroxyacetone phosphate.
AB  - A novel, mild, and efficient method was described to introduce a dibenzyl
      phosphate by ring opening of benzylglycidol mediated by Lewis acids. This
      methodology was used as a key step for synthesizing the dihydroxyacetone
      phosphate (DHAP) in only three steps with an overall yield of 74% from the
      commercially available racemic benzylglycidol.

PMID- 16956224
TI  - Rapid access to oxindoles by the combined use of an Ugi four-component reaction
      and a microwave-assisted intramolecular Buchwald-Hartwig amidation reaction.
AB  - A two-step sequence involving an Ugi four-component reaction (Ugi-4CR) and a
      palladium-catalyzed intramolecular amidation of aryl iodide has been developed
      for rapid access to functionalized oxindole (1). Microwave heating was used to
      accelerate and to improve the efficiency of the intramolecular Buchwald-Hartwig
      reaction.

PMID- 16956225
TI  - Halide ions as a highly efficient promoter in the Ru-catalyzed
      hydroesterification of alkenes and alkynes.
AB  - The presence of catalytic amounts of halide salts was found to enhance
      dramatically the reaction efficiency in the Ru-catalyzed hydroesterification of
      alkenes and alkynes using a chelating 2-pyridylmethyl formate by lowering the
      reaction temperature. On the basis of IR and NMR studies, the halide effect on
      the reaction is mainly attributed to the facile dissociation of the
      trirutheniumcarbonyl precursor into the presumed active metal species. With this
      milder condition, the substrate scope has been significantly broadened.

PMID- 16956226
TI  - [1,2]- or [2,3]-rearrangement of onium ylides of allyl and benzyl ethers and
      sulfides via in situ-generated iodonium ylides.
AB  - Iodonium ylides, generated in situ with bisacetoxyiodobenzene, are converted to
      allyl- or benzyl-substituted oxonium or sulfonium ylides via rhodium- or copper
      catalyzed carbene transfer. Except for the S-benzyl example, the resulting ylides
      undergo rearrangement to the corresponding 2-substituted heterocycles. This
      demonstrates the first use of iodonium ylides as diazoketone surrogates for the
      generation and rearrangement of onium ylide intermediates. This abbreviated one
      step method proceeds in comparable yields relative to the corresponding two-step
      route employing diazoketone intermediates.

PMID- 16956227
TI  - Bicyclic- and tricyclic-beta-lactones via organonucleophile-promoted bis
      cyclizations of keto acids: Enantioselective synthesis of (+)-dihydroplakevulin.
AB  - A highly diastereoselective, nucleophile-promoted bis-cyclization process,
      employing readily available and tractable keto acid substrates, is described.
      This methodology provides concise access to bicyclic- and tricyclic-beta-lactones
      bearing tertiary carbinol centers and quaternary carbons, greatly extending the
      scope of previous routes to bicyclic-beta-lactones from aldehyde acid substrates.
      The utility of the method was demonstrated by application to an enantioselective
      synthesis of (+)-dihydroplakevulin A. This and related processes may be revealing
      a subtle interplay between [2+2] cycloaddition and nucleophile-catalyzed aldol
      lactonization (NCAL) reaction manifolds.

PMID- 16956228
TI  - Readily available phosphine-phosphoramidite ligands for highly efficient Rh
      catalyzed enantioselective hydrogenations.
AB  - A new family of air- and moisture-stable phosphine-phosphoramidite ligands
      (PEAPhos) has been prepared from commercially available and inexpensive (S)-alpha
      phenylethylamine through a two- or three-step transformation and successfully
      applied in the rhodium-catalyzed enantioselective hydrogenations of a variety of
      substrates, in which up to 99.9% ee was obtained for all of these kinds of
      substrates.

PMID- 16956229
TI  - Oxidative Mannich reaction of N-carbobenzyloxy amines with 1,3-dicarbonyl
      compounds.
AB  - Efficient carbon-carbon bond formation at the alpha-position of nitrogen was
      established by one-pot oxidative Mannich reaction of N-carbobenzyloxy (Cbz)
      amines with 1,3-dicarbonyl compounds using N-tert-butylbenzenesulfinimidoyl
      chloride as an oxidant.

PMID- 16956230
TI  - Synthesis of a bistetrahydrofuran C17-C32 fragment of the polyether antibiotic
      ionomycin.
AB  - A Zn-initiated triepoxide cascade cyclization reaction was employed for the
      synthesis of the bistetrahydrofuran core segment of the polyether ionophore
      antibiotic ionomycin.

PMID- 16956231
TI  - Advances in Lewis acid controlled carbon-carbon bond-forming reactions enable a
      concise and convergent total synthesis of bullatacin.
AB  - Lewis acids control regioselectivity in the alkylation of epi-chlorohydrin and
      the stereochemistry of an alkyne addition to set the C24/C23 anti relationship.
      These advances facilitate an efficient total synthesis of bullatacin in 13.3%
      overall yield from commercial starting materials.

PMID- 16956233
TI  - Density functional theory prediction of enhanced photomagnetic properties of
      nitronyl nitroxide and imino nitroxide diradicals with substituded dihydropyrene
      couplers.
AB  - We predict the photoswitching magnetic properties of four substituted
      dihydropyrenes from density functional broken-symmetry calculations. The magnetic
      exchange coupling constants differ up to 9.44 cm(-1). The intramolecular exchange
      interactions are ferromagnetic in nature. The calculated coupling constants are
      much larger than those reported earlier for photomagnetic organic molecules.

PMID- 16956234
TI  - Master equation methods in gas phase chemical kinetics.
AB  - In this article, we discuss the application of master equation methods to
      problems in gas phase chemical kinetics. The focus is on reactions that take
      place over multiple, interconnected potential wells and on the dissociation of
      weakly bound free radicals. These problems are of paramount importance in
      combustion chemistry. To illustrate specific points, we draw on our experience
      with reactions we have studied previously.

PMID- 16956235
TI  - Study of the complexation of fisetin with cyclodextrins.
AB  - In this work, the interaction between fisetin (3,3',4',7-tetrahydroxyflavone)
      (Fis) and cyclodextrins (CDs) (alpha and beta) was studied through UV-vis
      absorption, steady-state fluorescence, induced circular dichroism, and (1)H NMR
      experiments with dependence on temperature and pH. Some experimental data were
      compared with quantum-mechanics studies based on the SAM1 (AMPAC) semiempirical
      model, as well as with the B3LYP and MPW1PW91 functional models from density
      functional theory using the 6-311G and 3-21G basis sets. The spectroscopic
      measurements show that Fis does not form stable complexes with alpha-CD. On the
      other hand, at pH 4.0 and 6.5, the complex Fis-beta-CD is formed in a Fis:beta-CD
      1:1 stoichiometry and an equilibrium constant (K) of 900 +/- 100 M(-1). In basic
      medium (pH 11.5), K decreases to 240 +/- 90 M(-1) because Fis deprotonation leads
      to its better solubilization in water. Molecular modeling points out that Fis is
      not totally inserted into the inner cavity of beta-CD. The formation of the
      inclusion complex renders an environment that enhances intramolecular excited
      state proton transfer. The inclusion complex is formed preferentially via entry
      of the Fis phenyl group into beta-CD.

PMID- 16956236
TI  - Effect of temperature and concentration on the structure of sec-butyl alcohol and
      isobutyl alcohol/water mixtures: near-infrared spectroscopic study.
AB  - The effect of temperature and concentration on the structure of sec-butyl alcohol
      and isobutyl alcohol/water binary mixtures in the alcohol-rich region (mole
      fraction of water X(H2O) < 0.3) has been studied using Fourier transform (FT)
      near-infrared (NIR) spectroscopy. The experimental data were analyzed by a two
      dimensional (2D) correlation approach and chemometric methods. It was found that
      molecules of both alcohols in the mixture with water are in the same environment
      as those in the pure alcohols. Even at very low water content (X(H2O) = 0.001) we
      did not observe water free from any specific interactions. The molecules of water
      are attached to the end free OH groups in the open chain associates of alcohol.
      In this way the structure of neat alcohol remains intact by addition of water.
      The water-alcohol interactions in sec-butyl alcohol and isobutyl alcohol/water
      mixtures are stronger than those in bulk water. The results obtained at higher
      water content or elevated temperatures indicate the possibility of water-water
      interaction. In the alcohol-rich region the hydrophobic effects are of minor
      importance and the structure and properties of these systems are determined by
      hydrogen bonding through the hydroxyl groups. Both alcohols behave similarly on
      the temperature or water content variation; the minor difference results from a
      different degree of self-association for sec-butyl alcohol and isobutyl alcohol.

PMID- 16956237
TI  - Control goal selection through anticorrelation analysis in the detection space.
AB  - A statistical method is reported to determine the pairs of fragment ions in a
      mass spectrum that are most susceptible to control by adaptive optimization of
      the laser pulse shapes in the strong-field regime. The proposed method is based
      on covariance analysis of the mass spectral fragmentation patterns generated by a
      set of randomly shaped pulses. The pairs of fragment ions that have higher
      negative covariances possess a correspondingly higher degree of controllability
      in an adaptive control experiment, whereas the pairs that have higher positive
      covariances possess correspondingly lower controllability.

PMID- 16956238
TI  - Calculation of vibrational spectra of linear tetrapyrroles. 4. Methine bridge C-H
      out-of-plane modes.
AB  - Quantum chemical force fields obtained by density functional theory (DFT)
      calculations systematically overestimate the frequencies of normal modes
      including ethylenic C-H out-of-plane (HOOP) coordinates. Compensation of this
      deviation requires a specific scaling factor for this type of coordinate that is
      distinctly lower than those applicable to out-of-plane coordinates in general.
      Such a specific scaling factor (0.900) has been optimized for the DFT(B3LYP)
      level of theory on the basis of vibrational analyses of training molecules
      including the HOOP coordinate. Thus, the root-mean-square deviation for the
      calculated frequencies of these modes is reduced from 16 to 8 cm(-1). Although
      Raman intensities are yet not reproduced in a satisfactory manner, implementation
      of the HOOP scaling factor into the set of global scaling factors determined
      previously (Magdo et al. J. Phys. Chem. A 1999, 103, 289-303) allows for a
      substantially improved reproduction of the experimental (resonance) Raman spectra
      of test molecules including linear methine-bridged tetrapyrroles. A very good
      agreement between calculated and experimental spectra is noted for the
      phycocyanobilin dimethylester dimer as well as for the protein-bound
      phycocyanobilin in the antenna pigment alpha-CPC. However, for the
      phycocyanobilin chromophore in the P(r) state of the plant photoreceptor
      phytochrome phyA, considerable deviations remain in the spectral range between
      800 and 500 cm(-1), which are attributed to the effect of specific protein
      chromophore interactions. The influence of the protein environment is not
      considered in the present calculations that refer to the molecule in vacuo.

PMID- 16956239
TI  - Reactions of early lanthanide metal atoms (Nd, Sm, Eu) with water molecules. A
      matrix isolation infrared spectroscopic and theoretical study.
AB  - The reactions of early lanthanide metal atoms Nd, Sm, and Eu with water molecules
      have been investigated using matrix isolation infrared spectroscopy and density
      functional calculations. The reaction intermediates and products were identified
      on the basis of isotopic labeled experiments and density functional frequency
      calculations. The ground state metal atoms react with water to form the M(H2O)
      and M(H2O)(2) complexes spontaneously on annealing (M = Nd, Sm, Eu). The M(H2O)
      complexes isomerize to the inserted HMOH molecules under red light irradiation,
      which further decompose to give the metal monoxides upon UV light irradiation.
      The Nd(H2O)(2) complex decomposes to form the trivalent HNd(OH)(2) molecule,
      while the Sm(H2O)(2) and Eu(H2O)(2) complexes rearrange to the divalent Sm(OH)(2)
      and Eu(OH)(2) molecules under red light irradiation.

PMID- 16956240
TI  - Origin of the attraction in aliphatic C-H/pi interactions: infrared spectroscopic
      and theoretical characterization of gas-phase clusters of aromatics with methane.
AB  - An attractive intermolecular interaction between an aliphatic C-H bond and a pi
      electron system (C-H/pi interaction) was characterized on the basis of infrared
      spectroscopy and high level ab initio calculations. Infrared spectroscopy was
      applied to several isolated methane clusters with benzene, toluene, p-xylene,
      mesitylene, and naphthalene in the gas phase, and the spectral changes of the C-H
      stretch bands in the methane moiety upon the cluster formation were observed. In
      the theoretical approach, interaction energies of the clusters were evaluated by
      high-level ab initio calculations. The forbidden symmetric C-H stretch transition
      weakly appeared in the IR spectra of the clusters, and it confirmed the small
      deformation of the methane moiety from the T(d)() symmetry, which was predicted
      by the ab initio calculations. On the other hand, the degenerated asymmetric C-H
      stretch band showed complicated splitting, which is qualitatively interpreted by
      a hindered rotor model. Low-frequency shifts upon the cluster formation were seen
      in the symmetric C-H stretch frequency, though the magnitude of the shifts was
      extremely small and no clear correlation with the interaction energy was found.
      On the other hand, the size of the calculated interaction energy well correlates
      with the polarizability of aromatics. The S(1)-S(0) electronic transition of the
      aromatic moiety was also observed, and it showed low-frequency shifts upon
      cluster formation. These results support the dominance of the dispersion
      interaction over the electrostatic and charge-transfer terms in the aliphatic C
      H/pi interaction.

PMID- 16956241
TI  - Insights into the mechanism of BN generation via boron triazide precursor:
      theoretical study.
AB  - Potential-energy surfaces for unimolecular decomposition of B(N3)(3) have been
      studied to understand the possible mechanism for BN generation. The decomposition
      of B(N3)(3) takes place on either the singlet and triplet surface, and both
      processes are high exothermic and obey sequential mechanisms. For the singlet
      reaction, the rate-determining step corresponds to cleavage of the first azide
      bond and linear (1)NBNN instead of (1)BN was suggested as the dominant product at
      room temperature. For the triplet surface, a fragment process from (3)BN(7) to
      (3)BN(5) is predicted to be the rate-determining step; once this barrier is
      counteracted, the subsequent decomposition processes could easily occur to form
      final product (3)BN. In addition, the possible mechanism for generating BN film
      via B(N3)(3) was discussed based on MC-SCF calculation results. These findings
      might be helpful in understanding the controllable decomposition of B(N3)(3) as
      well as its application in generating BN films.

PMID- 16956242
TI  - Solvent and pressure effects on quenching by oxygen of 9,10-dimethylanthracene
      fluorescence in liquid n-alkanes: a study on solvent cage effects.
AB  - The fluorescence quenching by oxygen of 9,10-dimethylanthracene (DMEA) in liquid
      ethane and propane at pressures up to 60 MPa and 25 degrees C was investigated.
      The apparent activation volumes for the quenching rate constant, k(q),DeltaV++(q)
      , were 5.0 +/- 3.4 and 7.4 +/- 1.0 cm(3)/mol, whereas those for the solvent
      viscosity, eta,DeltaV++(eta) , were 190 +/- 22 and 42 +/- 1 cm(3)/mol in ethane
      and propane at 6.0 MPa, respectively. These results were discussed together with
      those in n-alkanes (C(4)-C(7)) and methylcyclohexane (MCH) that were previously
      reported, and it was found that DeltaV++(q) increases monotonically but
      DeltaV++(eta) decreases rapidly with increasing the number of carbon atoms in n
      alkanes. The plot of ln k(q) against ln eta showed a leveling-off with decreasing
      eta. These observations were analyzed satisfactorily by the pressure dependence
      of the solvent viscosity on k(q) coupled with that of the radial distribution
      function, g(sigma), at contact with a hard sphere assumption. The apparent
      bimolecular rate constant, k(bim,0), for the quenching in the solvent cage was
      evaluated by extrapolating to g(sigma)eta = 0 in the plot of g(sigma)/k(q)
      against g(sigma)eta, and it was found that k(bim,0) decreased with increasing the
      radius of the solvent molecule. From the solvent size dependence of k(bim,0), the
      solvent cage effect was discussed phenomenologically.

PMID- 16956243
TI  - Reactions of methyl fluoride with atomic transition-metal and main-group cations:
      gas-phase room-temperature kinetics and periodicities in reactivity.
AB  - Reactions of CH(3)F have been surveyed systematically at room temperature with 46
      different atomic cations using an inductively coupled plasma/selected-ion flow
      tube tandem mass spectrometer. Rate coefficients and product distributions were
      measured for the reactions of fourth-period atomic ions from K(+) to Se(+), of
      fifth-period atomic ions from Rb(+) to Te(+) (excluding Tc(+)), and of sixth
      period atomic ions from Cs(+) to Bi(+). Primary reaction channels were observed
      corresponding to F atom transfer, CH(3)F addition, HF elimination, and H(2)
      elimination. The early-transition-metal cations exhibit a much more active
      chemistry than the late-transition-metal cations, and there are periodic features
      in the chemical activity and reaction efficiency that maximize with Ti(+), As(+),
      Y(+), Hf(+), and Pt(+). F atom transfer appears to be thermodynamically
      controlled, although a periodic variation in efficiency is observed within the
      early-transition-metal cations which maximizes with Ti(+), Y(+), and Hf(+).
      Addition of CH(3)F was observed exclusively (>99%) with the late-fourth-period
      cations from Mn(+) to Ga(+), the fifth-period cations from Ru(+) to Te(+), and
      the sixth-period cations from Hg(+) to Bi(+) as well as Re(+). Periodic trends
      are observed in the effective bimolecular rate coefficient for CH(3)F addition,
      and these are consistent with expected trends in the electrostatic binding
      energies of the adduct ions and measured trends in the standard free energy of
      addition. HF elimination is the major reaction channel with As(+), while
      dehydrogenation dominates the reactions of W(+), Os(+), Ir(+), and Pt(+).
      Sequential F atom transfer is observed with the early-transition-metal cations,
      with the number of F atoms transferred increasing across the periodic table from
      two to four, maximizing at four for the group 5 cations Nb(+)(d(4)) and
      Ta(+)(d(3)s(1)), and stopping at two with V(+)(d(4)). Sequential CH(3)F addition
      was observed with many atomic cations and all of the metal mono- and
      multifluoride cations that were formed.

PMID- 16956244
TI  - A new approach to determining gas-particle reaction probabilities and application
      to the heterogeneous reaction of deliquesced sodium chloride particles with gas
      phase hydroxyl radicals.
AB  - The reaction kinetics for gaseous hydroxyl radicals (OH) with deliquesced sodium
      chloride particles (NaCl(aq)) were investigated using a novel experimental
      approach. The technique utilizes the exposure of substrate-deposited aerosol
      particles to reactive gases followed by chemical analysis of the particles using
      computer-controlled scanning electron microscopy with energy-dispersive analysis
      of X-rays (CCSEM/EDX) capability. Experiments were performed at room temperature
      and atmospheric pressure with deliquesced NaCl particles in the micron size range
      at 70-80% RH and with OH concentrations in the range of 1 to 7 x 10(9) cm(-3).
      The apparent, pseudo first-order rate constant for the reaction was determined
      from measurements of changes in the chloride concentration of individual
      particles upon reaction with OH as a function of the particle loading on the
      substrate. Quantitative treatment of the data using a model that incorporates
      both diffusion and reaction kinetics yields a lower limit to the net reaction
      probability of gamma(net) > or = 0.1, with an overall uncertainty of a factor of
      2.

PMID- 16956245
TI  - Rise in the pH of an unfrozen solution in ice due to the presence of NaCl and
      promotion of decomposition of gallic acids owing to a change in the pH.
AB  - Oxidative decomposition of gallic acid occurs in alkaline solutions but hardly
      arises in acidic solutions. We have found that the addition of sodium chloride
      promotes the decomposition of gallic acid caused by freezing even under neutral
      and acidic conditions. Even at pH 4.5, gallic acid was decomposed by freezing in
      the presence of NaCl; however, in the absence of NaCl, it was hardly decomposed
      by freezing at pH lower than 7. Chloride ions are more easily incorporated in ice
      than sodium ions when the NaCl solution is frozen. The unfrozen solution in ice
      becomes positively charged, and as a result, protons transfer from the unfrozen
      solution to the ice. We measured the pH in the unfrozen solution which coexists
      with single-crystal ice formed from a 5 mmol dm(-3) NaCl solution and determined
      the pH to be 8.6 at equilibrium with CO(2) of 380 ppm or 11.3 in the absence of
      CO(2) compared to pH 5.6 in the original solution. From the model calculation
      performed for gallic acid solution in the presence of 5 mmol dm(-3) NaCl, it can
      be estimated that the amount of OH(-) transferred from the ice to the solution
      corresponds to 1.26 x 10(-5) mol dm(-3). The amount of OH(-) transferred is
      concentrated into the unfrozen solution and affects the pH of the unfrozen
      solution. Therefore, the pH in an unfrozen gallic acid solution in ice becomes
      alkaline, and the decomposition of gallic acid proceeds. It is expected that
      other base-catalyzed reactions in weakly acidic solutions also proceed by
      freezing in the presence of NaCl without the need for any alkaline reagents.

PMID- 16956246
TI  - Structure of the boronic acid dimer and the relative stabilities of its
      conformers.
AB  - Despite the widespread use of boronic acids in materials science and as
      pharmaceutical agents, many aspects of their structure and reactivity are not
      well understood. In this research the boronic acid dimer, [HB(OH)(2)](2), was
      studied by second-order Moller-Plesset (MP2) perturbation theory and coupled
      cluster methodology with single and double excitations (CCSD). Pople split
      valence 6-31+G*, 6-311G**, and 6-311++G** and Dunning-Woon correlation-consistent
      cc-pVDZ, aug-cc-pVDZ, cc-pVTZ, and aug-cc-pVTZ basis sets were employed for the
      calculations. A doubly hydrogen-bonded conformer (1) of the dimer was
      consistently found to be lowest in energy; the structure of 1 was planar (C(2h))
      at most computational levels employed but was significantly nonplanar (C(2)) at
      the MP2/6-311++G** and CCSD/6-311++G** levels, the result of an intrinsic problem
      with Pople-type sp-diffuse basis functions on heavy atoms. The dimerization
      energy, enthalpy, and free energy for the formation of (1) from the exo-endo
      conformer of the monomer were -10.8, -9.2, and +1.2 kcal/mol, respectively, at
      the MP2/aug-cc-pVTZ level. Several other hydrogen-bonded conformers of the dimer
      were local minima on the potential energy surface (PES) and ranged from 2 to 5
      kcal/mol higher in energy than 1. Nine doubly OH-bridged conformers, in which the
      boron atoms were tetracoordinated, were also local minima on the PES, but they
      were all greater than 13 kcal/mol higher in energy than 1; doubly H-bridged
      structures proved to be transition states. MP2 and CCSD results were compared to
      those from the BLYP, B3LYP, OLYP, O3LYP, PBE1PBE, and TPSS functionals with the 6
      311++G** and aug-cc-pVTZ basis sets; the PBE1PBE functional performed best
      relative to the MP2 and CCSD results. Self-consistent reaction field (SCRF)
      calculations predict that boronic acid dimerization is less favorable in solution
      than in vacuo.

PMID- 16956247
TI  - Theoretical studies on the low-lying electronic states of the HSO neutral radical
      and its cation.
AB  - Using the complete active space self-consistent field (CASSCF) method with large
      atomic natural orbital (ANO-L) basis set, four electronic states of the HSO
      neutral radical are optimized. The vertical transitions of the HSO neutral
      radical are investigated by using the same method under the basis set of ANO-L
      functions augmented with a series of adapted 1s1p1d Rydberg functions, through
      which eight valence states and eight Rydberg states are probed. Ionic states of
      the HSO neutral radical are extensively studied in both cases of the adiabatic
      and vertical ionization, from which the relatively complete understanding of
      ionization energies is given. To include further correlation effects, the second
      order perturbation method (CASPT2) is implemented, and the comparison between
      CASSCF and CASPT2 methods is performed.

PMID- 16956248
TI  - Comment on the paper "On the limits of highest-occupied molecular orbital driven
      reactions: the frontier effective-for-reaction molecular orbital concept".

PMID- 16956250
TI  - Novel nanotubes from a cationic surfactant and an anionic stiff aromatic counter
      ion.
AB  - A novel class of nanotubes (NT) is reported which consists of two components, a
      cationic surfactant cetyltrimethylammoniumbromide (CTAB) and an anionic UV
      absorber, 2-phenylbenzimidazole-5-sulfonic acid (PBSA). When aqueous solutions of
      the components are mixed, a turbid low-viscosity solution is formed immediately.
      This solution is stable for several days. Then, within 1 day, the turbid samples
      are transformed into transparent, isotropic soft gels that contain thin single
      walled tubuli (SWNT). The SWNT have been characterized by cryo-TEM micrographs.
      The NT have an extremely narrow size distribution of the outer (o.d.) and inner
      (i.d.) diameters. The tubes have an o.d. of 13 +/- 0.5 nm and an i.d. of about 6
      nm. Despite their small diameter, the NT are extremely stiff with a persistence
      length l(p) greater than several micrometers. It is assumed that the tubuli
      consist of bilayers of the cationic and anionic compounds with a one-to-one
      ratio. In solution, the tubuli seem to be stabilized by the adsorption of one of
      the excess amphiphilic compounds.

PMID- 16956251
TI  - Grazing angle mirror-backed reflection (GMBR) for infrared analysis of monolayers
      on silicon.
AB  - An easy handling infrared measurement, grazing angle mirror-backed reflection
      (GMBR), has been established to analyze the silicon-based organic monolayer.
      Theoretical prediction gave the optimal configuration with p-polarized
      irradiation near a grazing angle 78.1 degrees of incidence. Experimental
      measurement of hydrogen-terminated, undecylenic acid (UA) and N
      hydroxysuccinimide (NHS) functionalized silicon (111) surfaces showed good signal
      peaks and reproducibility.

PMID- 16956252
TI  - Stabilization of platinum clusters by substitutional boron dopants in carbon
      supports.
AB  - To stabilize platinum clusters on carbon supports, carbon substituted boron
      dopants were introduced in graphite and fullerene models, and the binding
      energies of Pt(1) to Pt(6) clusters on the carbon supports were investigated
      using first-principles density functional theory (DFT) calculations. The
      adsorption energies of the Pt clusters increased significantly in the presence of
      boron. The adsorption energies of Ru(1) and Au(1) were also found to dramatically
      increase in the presence of boron.

PMID- 16956253
TI  - Carbon-coated core shell structured copper and nickel nanoparticles synthesized
      in an ionic liquid.
AB  - A simple synthetic route to prepare carbon-coated copper or nickel nanoparticles
      is developed in an ionic liquid under microwave heating. The obtained products
      are characterized by XRD, UV-spectroscopy, and Raman spectroscopy. The
      morphologies are studied with the help of TEM, HRSEM, and HRTEM. A bulk transport
      property for carbon coated nickel is reported in this letter.

PMID- 16956254
TI  - Recombination and transport processes in dye-sensitized solar cells investigated
      under working conditions.
AB  - The transport and recombination of electrons in dye-sensitized TiO(2) solar cells
      were studied by analysis of the current and voltage response to a small square
      wave light-intensity modulation. Solar cells were studied under working
      conditions by using potentiostatic and galvanostatic conditions. An increase in
      applied voltage, that is, from 0 V toward open-circuit voltage, was found to lead
      to faster electron transport at low light intensities, while it slowed transport
      at higher light intensities. This observation seems to be conflicting with the
      multiple trapping model with diffusive transport. An effective diffusion length
      at the maximum power point was calculated, and it was shown that it decreases
      with increasing light intensity.

PMID- 16956255
TI  - Predicting catalysis: understanding ammonia synthesis from first-principles
      calculations.
AB  - Here, we give a full account of a large collaborative effort toward an atomic
      scale understanding of modern industrial ammonia production over ruthenium
      catalysts. We show that overall rates of ammonia production can be determined by
      applying various levels of theory (including transition state theory with or
      without tunneling corrections, and quantum dynamics) to a range of relevant
      elementary reaction steps, such as N(2) dissociation, H(2) dissociation, and
      hydrogenation of the intermediate reactants. A complete kinetic model based on
      the most relevant elementary steps can be established for any given point along
      an industrial reactor, and the kinetic results can be integrated over the
      catalyst bed to determine the industrial reactor yield. We find that, given the
      present uncertainties, the rate of ammonia production is well-determined directly
      from our atomic-scale calculations. Furthermore, our studies provide new insight
      into several related fields, for instance, gas-phase and electrochemical ammonia
      synthesis. The success of predicting the outcome of a catalytic reaction from
      first-principles calculations supports our point of view that, in the future,
      theory will be a fully integrated tool in the search for the next generation of
      catalysts.

PMID- 16956256
TI  - Spectroscopy and transport of the triplet exciton in a terthiophene end-capped
      poly(phenylene ethynylene).
AB  - Triplet states of poly(phenylene ethynylene), (3)PPE(*), not easily formed by
      direct photoexcitation, were produced by pulse radiolysis in toluene, along with
      triplet states of T(3)PPE having terthiophene end-caps. Intense triplet-triplet
      absorption maxima, epsilon(680)((3)PPE(*)) = 9.5 x 10(4) M(-1) cm(-1) and
      epsilon(780)((3)T(3)PPE(*)) = 2.8 x 10(4) M(-1) cm(-1) enable identification of
      these two species, which have triplet energies of 2.12 and 1.77 eV determined in
      bimolecular energy transfer equilibria. Bleaching of ground-state absorption
      measures (3)PPE(*) to be the delocalized over a 1.8-nm length. Triplet states
      formed in the PPE chains were transported to and trapped by the end caps in a
      time <<5 ns.

PMID- 16956257
TI  - Changes in electronic structure upon Li insertion reaction of monoclinic
      Li3Fe2(PO4)3.
AB  - The electrochemical lithium insertion reaction of monoclinic Li(3)Fe(2)(PO(4))(3)
      as cathode materials of lithium-ion batteries was investigated from the viewpoint
      of the electronic structure around Fe and the polyanion unit (PO(4)). Fe K-edge
      and L(III,II)-edge XAS measurements revealed that Fe(3+) was reduced to Fe(2+)
      upon Li insertion. In addition, O K-edge and P K-edge XAS also showed spectral
      changes upon Li insertion, which corresponded to changes in the electronic
      structure of the PO(4) polyanion unit. The ab initio density functional
      calculation was performed within the GGA and LDA+U methods. The LDA+U method
      reproduced well the cell potential upon lithium intercalation into
      Li(3)Fe(2)(PO(4))(3), whereas the GGA method underestimated the intercalation.
      The calculated electronic structure of Li(3)Fe(2)(PO(4))(3) described strong P 3p
      O 2p covalent bonding, while weak hybridization was indicated in Fe 3d-O 2p.
      Moreover, the difference in electronic density between Li(3)Fe(2)(PO(4))(3) and
      the lithiated model indicated that the polarization effect between inserted Li
      and oxygen induced the changes in the electronic structure around the polyanion
      unit.

PMID- 16956258
TI  - Pi* orbital system of alternating phenyl and ethynyl groups: measurements and
      calculations.
AB  - The temporary anion states of a series of alternating phenyl-ethynyl compounds
      are studied by means of electron transmission spectroscopy. Calculations of the
      virtual orbital energies of these compounds are computed with ab initio HF
      methods as well as DFT, and excellent correlations with the experimental vertical
      attachment energies are obtained. Scaled orbital energies for long-chain
      molecules are used to predict the vertical attachment energies of these
      compounds. In the absence of scaling, HOMO-LUMO gaps computed by DFT are found to
      be in substantial disagreement with gas-phase data. Such discrepancies may cause
      significant errors in theoretical studies of molecular conductance.

PMID- 16956259
TI  - A family of stable silica fullerenes with fully coordinated structures.
AB  - Theoretical electronic structure techniques have become an indispensable and
      powerful tool for predicting molecular properties and designing new materials.
      The discovery of C(60) opened a challenging field in nanoscale materials science,
      and since then people have been looking for its inorganic analogues. On the basis
      of the B3LYP/6-31G(d) calculations, here we provide theoretical evidence for a
      family of stable silica fullerenes with fully coordinated structures, which
      exhibit highly structural and energetic stabilities, very large energy gaps, and
      extremely good resistibilities to breakdown of the insulating capability in an
      applied electric field. Our calculations indicate that the discrete silica
      fullerenes are a possible polymorph of silica and can be synthesized under some
      conditions. They are expected to find novel applications in silica-based
      molecular devices. The present results may provide an aid in the experimental
      design for controllably producing desired silica clusters.

PMID- 16956260
TI  - Precipitation of nanostructured copper oxalate: substructure and growth
      mechanism.
AB  - The possibility of controlling materials properties by tailoring their
      substructure at the nanometer scale is a current topic of great interest. To do
      so, a fundamental understanding of the growth mechanism is of key importance and
      an analytical challenge as nanostructured materials are often produced by
      precipitation methods at high supersaturations where formation kinetics are fast.
      The current study focuses on the precipitation of copper oxalate, which has been
      previously shown to produce self-assembled ordered nanostructured particles with
      the promise of being able to tailor this nanometer substructure. In the current
      study we investigate in detail the growth mechanism and kinetics of precipitation
      by using in-situ particle size measurement or by stopping the reaction at various
      stages and using ex-situ methods. Combining the ex-situ methods of high
      resolution scanning electron microscopy, transmission electron microscopy, and X
      ray powder diffraction along with the in-situ methods, we were able to follow the
      growth process from 2 min to 2 weeks. The results in the 2-30 min period lead to
      the proposal of a core-shell growth model with a poorly ordered core and a well
      structured shell of nanosized crystallites (50-70 nm), adding support to the
      brick-by-brick model previously proposed for this phase of particle growth.
      Particle evolution over long periods up to 2 weeks show a ripening which produces
      lens-shaped particles that eliminate the "high" surface energy faces observed in
      the earlier stages of growth. A more complete growth mechanism for copper oxalate
      precipitation at moderate supersaturations is proposed similar to recent findings
      for other self-assembled nanostructured particles.

PMID- 16956261
TI  - Pseudoisocyanine J-aggregate to optical waveguiding crystallite transition:
      microscopic and microspectroscopic exploration.
AB  - Using fluorescent microscopy and microspectroscopy, optical properties and
      morphology transformations in individual pseudoisocyanine (PIC) J-aggregates in
      aqueous electrolyte solutions have been explored. A stringlike structure of J
      aggregates with a string diameter much less than 1 microm has been observed.
      Photodestruction of the strings under short-wavelength excitation has been
      revealed. Rodlike PIC crystallites, about 1 microm in diameter, have been
      observed with time. The fluorescence spectrum of rodlike crystallites has been
      found to differ from that of stringlike J-aggregate and from PIC crystal powder
      spectra. The crystallites are very stable, and their photodestruction has not
      been observed under any excitation conditions. It has been found that rodlike
      crystallites in contrast to stringlike J-aggregates possess optical waveguide
      properties. The luminescence of crystallites can be observed only at the
      excitation spot and at butt ends located up to hundreds of micrometers from the
      excitation spot.

PMID- 16956262
TI  - Molecular simulation of carbon dioxide/methane/hydrogen mixture adsorption in
      metal-organic frameworks.
AB  - This work performs a systematic computational study toward a molecular
      understanding of the separation characteristics of metal-organic frameworks
      (MOFs), for which the purification of synthetic gas by two representative MOFs,
      MOF-5 and Cu-BTC, is adopted as an example. The simulations show that both
      geometry and pore size affect largely the separation efficiency, complex
      selectivity behaviors with different steps can occur in MOFs, and the
      electrostatic interactions that exist can enhance greatly the separation
      efficiency of gas mixtures composed of components with different chemistries.
      Furthermore, the macroscopic separation behaviors of the MOF materials are
      elucidated at a molecular level to give insight into the underlying mechanisms.
      The findings as well as the molecular-level elucidations provide useful
      microscopic information toward a complete understanding of the separation
      characteristics of MOFs that may lead to general design strategies for
      synthesizing new MOFs with tailored properties, as well as guiding their
      practical applications.

PMID- 16956263
TI  - Electrochemically deposited organic luminescent films: the effects of deposition
      parameters on morphologies and luminescent efficiency of films.
AB  - The electropolymerization behaviors of an electroactive and luminescent compound
      TCPC as precursor are studied. The resultant electrochemical deposition (ED)
      films are characterized by cyclic voltammetry (CV), UV-vis, fluorescence spectra,
      scanning electron microscopy (SEM), and atomic force microscopy (AFM). Under the
      CV mode with potential range of -0.5 to 0.85 V vs Ag/Ag(+), the coupling
      reactions between the carbazole units of TCPC are very efficient, while the
      fluorescent trifluorene segment in TCPC is chemically inert in this potential
      range, which results in a highly fluorescent film formation on indium tin oxide
      (ITO) electrode. The deposition parameters for preparing the TCPC-based ED films
      are optimized, and the best ED film gives the fluorescence efficiency of 45.5%
      with surface roughness of 2.8 nm and morphologic stability as heating to 180
      degrees C. The light-emitting devices (LEDs) using this ED film as light emitting
      layer with structure ITO/ED film (approximately 100 nm)/Ba/Al achieve maximum
      luminescence and external quantum efficiency of 4224 cd/m(2) at 17 V and 0.72% at
      11.5 V, respectively, which are better than the device using TCPC spin-coating
      films as emitting layer. The technique provides a facile route toward a
      patternable luminescent film and device because such luminescent ED films can be
      manipulatively deposited on the electrified electrode.

PMID- 16956264
TI  - Photophysical properties and photocatalytic activities of bismuth molybdates
      under visible light irradiation.
AB  - Aurivillius structure Bi(2)MoO(6) (BG: 2.70 eV) that is a low-temperature phase
      showed an intense absorption band in the visible light region and photocatalytic
      activity for O(2) evolution from an aqueous silver nitrate solution under visible
      light irradiation, among various bismuth molybdates (Bi(2)MoO(6), Bi(2)Mo(2)O(9),
      and Bi(2)Mo(3)O(12)) synthesized by solid-state and reflux reactions.
      Bi(2)Mo(3)O(12) (BG: 2.88 eV) also showed photocatalytic activity for O(2)
      evolution under full-arc irradiation of a Xe lamp (lambda > 300 nm). The
      photocatalytic activity of the Aurivillius structure Bi(2)MoO(6) prepared by the
      reflux method was dependent on the annealing temperature after the preparation.
      The crystallinity was the important factor for the activity. Calculation by the
      density functional method indicated that the conduction band of Aurivillius
      structure Bi(2)MoO(6) was made up of Mo 4d orbitals. It turned out that the
      visible-light absorption of this photocatalyst was due to the transition from the
      valence band consisting of O 2p orbitals to the conduction band. The corner
      sharing structure of the MoO(6) octahedra contributed to the visible light
      response and the photocatalytic performance because excitation energy and/or
      photogenerated electron and hole pairs began to migrate easily in the Aurivillius
      structure.

PMID- 16956265
TI  - Structural and spectroscopic properties of pure and doped Ba6Ti2Nb8O30 tungsten
      bronze.
AB  - Pure and doped Ba(6)Ti(2)Nb(8)O(30) (BTN), obtained by substituting M = Cr, Mn,
      or Fe on the Ti site (Ba(6)Ti(2-x) M(x)Nb(8)O(30), x = 0.06 and 0.18) and Y and
      Fe on the Ba and Ti sites, respectively (Ba(6-x)Y(x)Ti(2-x)Fe(x)Nb(8)O(30), x=
      0.18), are synthesized. The influence of cation doping on the local structure,
      the cation oxidation state, and the possible defect formation able to maintain
      the charge neutrality are investigated by spectroscopic (electron paramagnetic
      resonance (EPR) and micro-Raman), structural (X-ray powder diffraction) and
      transport (impedance spectroscopy, thermoelectric power) measurements, in the
      temperature range of 300-1200 K in air and N(2) flow. Starting from the valence
      state of the doping ions (Fe(3+), Cr(3+), and Mn(2+)), determined by EPR, and
      from thermoelectric power measurements, evidencing a negative charge transport,
      different charge-compensating defect equilibria, based on the creation of
      positive electron holes or oxygen vacancies and electrons, are discussed to
      interpret the conductivity results.

PMID- 16956266
TI  - Synthesis of hematite (alpha-Fe2O3) nanorods: diameter-size and shape effects on
      their applications in magnetism, lithium ion battery, and gas sensors.
AB  - We demonstrated in this paper the shape-controlled synthesis of hematite (alpha
      Fe(2)O(3)) nanostructures with a gradient in the diameters (from less than 20 nm
      to larger than 300 nm) and surface areas (from 5.9 to 52.3 m(2)/g) through an
      improved synthetic strategy by adopting a high concentration of inorganic salts
      and high temperature in the synthesis systems to influence the final products of
      hematite nanostructures. The benefits of the present work also stem from the
      first report on the <20-nm-diameter and porous hematite nanorods, as well as a
      new facile strategy to the less-than-20-nm nanorods, because the less-than-20-nm
      diameter size meets the vital size domain for magnetization properties in
      hematite. Note that the porous and nonporous hematite one-dimensional
      nanostructures with diameter gradients give us the first opportunity to
      investigate the Morin temperature evolution of nanorod diameter and porosity.
      Evidently, the magnetic properties for nanorods exhibit differences compared with
      those for the spherical particle counterparts. Hematite nanorods are strongly
      dependent on their diameter size and porosity, where the magnetization is not
      sensitive to the size evolution from submicron particles to the 60-90 nm
      nanorods, while the magnetic properties change significantly in the case of <20
      nm. In other words, for the magnetic properties of nanorods, in a comparable size
      range, the porous existence could also influence the magnetic behavior. Moreover,
      applications in formaldehyde (HCHO) gas sensors and lithium batteries for the
      hematite nanostructures with the diameter/surface area gradient reveal that the
      performance of electrochemical and gas-sensor properties strongly depends on the
      diameter size and Brunauer-Emmett-Teller (BET) surface areas, which is consistent
      with the crystalline point of view. Thus, this work not only provides the first
      example of the fabrication of hematite nanostructure sensors for detecting HCHO
      gas, but also reveals that the surface area or diameter size of hematite nanorods
      can also influence the lithium intercalation performances. These results give us
      a guideline for the study of the size-dependent properties for functional
      materials as well as further applications for magnetic materials, lithium-ion
      batteries, and gas sensors.

PMID- 16956267
TI  - Bacillus subtilis assisted assembly of gold nanoparticles into long conductive
      nodous ribbons.
AB  - Gold nanopraticles with diameters of about 20 nm were assembled onto the surfaces
      of Bacillus subtilis by keeping the mixture of the nanoparicles and the bacteria
      in the dark without disturbance for over a month. During the aging process, the
      bacteria connected to each other end-to-end to form long wires and gold
      nanoparticles were coated compactly onto the surfaces of the wires
      simultaneously. The resulting composite wires were collapsed into ribbons with a
      width of about 1 microm after drying in air. The ribbons present a novel
      structure with nodes on their backbones and have lengths of several millimeters.
      They are conductive and showed Ohmic behavior, which provides potential
      applications in the fabrication of electronic nanodevices.

PMID- 16956268
TI  - Mechanisms of amine-catalyzed organosilicate hydrolysis at circum-neutral pH.
AB  - Mono- and polyamines can catalyze the hydrolysis and condensation of
      organosilicate starting materials in biomimetic silica synthesis pathways at
      circum-neutral pHs and room temperature. Our study is focused on understanding
      the mechanistic role of amines in catalyzing the hydrolysis process that precedes
      condensation. We have conducted (29)Si NMR experimental studies over a range of
      temperature and pHs for the hydrolysis rates of trimethylethoxysilane (TMES), a
      model compound with only one hydrolyzable bond, combined with quantum mechanical
      hybrid density functional theory calculations of putative intermediate and
      transition-state structures for TMES and tetramethyl orthosilicate (TMOS).
      Comparison of calculated energies with experimentally determined activation
      energies indicates that amine catalysis of TMES is primarily a consequence of the
      amine's acidity at neutral pH. The proton released by the amine is transferred to
      the organosilicate, producing a protonated ethoxy leaving group that can be
      displaced by water in an S(N)2 reaction. For TMOS, the activation energy of
      proton-transfer coupled with S(N)2 substitution is comparable to that for
      Corriu's nucleophile-activated nucleophilic displacement, such that the mechanism
      of amine-catalyzed hydrolysis is dependent mostly on the ambient pH conditions as
      well as the type of amine. The relevance of our results to biological silica
      precipitation is discussed.

PMID- 16956269
TI  - Research on the vesicle-micelle transition by 1H NMR relaxation measurement.
AB  - We have investigated how the dynamics of surfactant molecules changes with the
      vesicle-micelle transition by (1)H NMR relaxation studies on the sodium decyl
      sulfate (SDeS)-decyltrimethylammonium bromide (DeTAB)-deuterium oxide system. The
      study has been planned with reference to the phase diagram of the SDeS-DeTAB
      water system deduced from thermodynamic analysis of the surface tension data. The
      spin-lattice relaxation time (T(1)) and the spin-spin relaxation time (T(2)) are
      measured at 90 and 400 MHz at various total molalities, m, and compositions,
      X(2), of the surfactants. The data were analyzed according to the "two-step"
      model developed by Wennerstrom et al. and molecular dynamics of the surfactant is
      discussed from the viewpoint of correlation time tau(f) associated with the local
      fast motion of the surfactant molecule, correlation time tau(s) associated with
      the slow overall motions of the aggregate and surfactant molecules within it, and
      local order parameter S. We find tau(s) of vesicles is an order of magnitude
      larger than that of micelles signifying that the tumbling of vesicle particles
      and surfactant diffusion over the vesicle are much slower than those for micelle.
      Tau(f) and S for vesicles are also larger than those for micelles. Molecular
      environments of the surfactant are also discussed from the dependence of the
      chemical shifts on m at constant X(2) or from that on X(2) at constant m. When
      the chemical shifts in vesicle and micelle are compared at constant m, the
      chemical shifts in vesicle are displaced to a lower magnetic field than those in
      micelle, which implies that the surfactant molecules are arranged more closely to
      each other in the vesicle than in the micelle.

PMID- 16956270
TI  - Stabilization of gold nanoparticles by 6-mercaptopurine monolayers. Effects of
      the solvent properties.
AB  - 6-Mercaptopurine-coated gold nanoparticles (6MP-AuNPs) have been prepared by
      modification of the nanoparticle surface with 6MP upon displacement of the
      protective layer of citrate anions. The modification has been studied by UV-vis
      and FTIR spectroscopies. A study of the stability of these 6MP-AuNPs in aqueous
      solutions as a function of ionic strength and pH has shown the importance of the
      charges on the stabilization. The protonation of N9 of the 6MP molecules brings
      about a sudden flocculation phenomenon. However, the flocculation is reversible
      upon changing the pH to values where the molecules become newly charged. Evidence
      of the competence between the interaction of capping solvent molecules and the
      attractive forces between particles is also shown in this paper.

PMID- 16956271
TI  - Simple solvothermal route to synthesize ZnO nanosheets, nanonails, and well
      aligned nanorod arrays.
AB  - ZnO nanosheets, nanonails, and well-aligned nanorods were fabricated on Zn foils
      by a solvothermal approach using ethanol as the solvent. A lower synthesis
      temperature and a shorter time period favor the formation of nanosheets. By
      optimizing the synthesis temperature and time period, ZnO nanonails with a
      hexagonal cap and a long stem could be produced. A higher temperature was not
      favorable to produce uniform and smooth nanorods. Well-aligned ZnO nanorod arrays
      were produced with diameters within 100-250 nm and lengths up to approximately 6
      microm when NaOH was added to the solvent. By optimizing the reaction parameters,
      the morphology, size, and orientation of the nanoforms could be tailored. The ZnO
      nanorods exhibit an excitonic strong UV emission and a defect-related broad green
      emission at room temperature. The defect-related green emission band decreased
      with the improvement of the degree of alignment of the nanorods.

PMID- 16956272
TI  - One-dimensional hierarchical layered KxMnO2 (x < 0.3) nanoarchitectures:
      synthesis, characterization, and their magnetic properties.
AB  - One-dimensional (1D) hierarchical nanostructures of ultralong layered K(x)MnO(2)
      (x < 0.3) bundles with diameters 50-100 nm and lengths up to 50-100 microm have
      been successfully prepared by a PEG-assisted hydrothermal method based on the
      reaction of KMnO(4) with 2-ethylhexanol. The obtained samples ascribe to the
      monoclinic phase and exhibit ferromagnetic behaviors below 32 K and paramagnetic
      behaviors above 32 K, which may make this system a promising base material for
      magnetic devices. A series of contrastive experiments have illustrated that 2
      ethylhexanol, PEG 400, KOH, and reaction time play an important role in the
      synthesis of the nanobundles. A possible growth mechanism has been proposed.

PMID- 16956273
TI  - Effects of surface oxygen vacancies on photophysical and photochemical processes
      of Zn-doped TiO2 nanoparticles and their relationships.
AB  - In this paper, TiO(2) nanoparticles doped with different amounts of Zn were
      prepared by a sol-gel method and were mainly characterized by means of X-ray
      photoelectron spectroscopy (XPS), photoluminescence (PL), and surface
      photovoltage spectrum (SPS). The effects of surface oxygen vacancies (SOVs) of Zn
      doped TiO(2) nanoparticles on photophysical and photocatalytic processes were
      investigated along with their inherent relationships. The results show that the
      SOVs easily bind photoinduced electrons to further give rise to PL signals. The
      SOVs can result in an interesting sub-band SPS response near the band edge in the
      TiO(2) sample consisting of much anatase and little rutile, except for an obvious
      band-to-band SPS response. Moreover, the intensities of PL and SPS signals of
      TiO(2), as well as the photocatalytic activity for degrading phenol solution, can
      be enhanced by doping an appropriate amount of Zn. These improvements are mainly
      attributed to the increase in the SOV amount. It can be suggested that the SOVs
      should play an important role during the processes of PL, surface photovoltage,
      and photocatalytic reactions, and, for the as-prepared TiO(2) samples doped with
      different amounts of Zn by thermal treatment at 550 degrees C, the larger the SOV
      amount, the stronger the PL and SPS signal, and the higher the photocatalytic
      activity.

PMID- 16956274
TI  - DFT description on electronic structure and optical absorption properties of
      anionic S-doped anatase TiO2.
AB  - Plane-wave-based pseudopotential density functional theory (DFT) calculations are
      used to characterize the doping effect of S substituting for O in anatase TiO(2).
      Through band structure calculation, a direct band gap is predicted in TiO(2)(
      )(x)S(x). Electronic structure analysis shows that the doping S could
      substantially lower the band gap of TiO(2) by the presence of an impurity state
      of S 3p on the upper edge of the valence band. Excitations from the impurity
      state of S 3p to the conduction band may be responsible for the red shift of the
      absorption edge observed in the S-doped TiO(2). The band gap lowering and red
      shift of the absorption edge are found to increase as the sulfur concentration
      increases.

PMID- 16956275
TI  - First-principles study on proton dissociation properties of fluorocarbon- and
      hydrocarbon-based membranes in low humidity conditions.
AB  - We present a theoretical study on the proton dissociation properties of the
      membranes for polymer electrolyte fuel cells. A density functional theory method
      is used to study the influence of fluorocarbon and hydrocarbon backbones on
      proton dissociation, the interaction of water molecules with the sulfonic acid
      group, and the energy barriers for proton dissociation. Better proton
      dissociation properties of CH(3)SO(3)H compared to CF(3)SO(3)H are observed from
      statistical analyses of the optimized structures for both systems. However, the
      calculated energy barriers for proton dissociation are lower for CF(3)SO(3)H than
      for the CH(3)SO(3)H system. At the same time, the interaction of water molecules
      is stronger for CH(3)SO(3)H than for CF(3)SO(3)H. Also, the analysis of the
      hydrogen-bonding network in both systems shows that the number of hydrogen bonds
      formed around the sulfonic acid group in CH(3)SO(3)H is larger than that in
      CF(3)SO(3)H. Therefore, the decrease of the energy barrier with increasing number
      of coordinating water molecules, pronounced in the case of CH(3)SO(3)H, may lower
      the barrier, which enhances good proton conductivity of a hydrocarbon-based
      polymer in low humidity conditions. Thus the hydration ability of a sulfonic acid
      group is an important factor for realizing better proton dissociation in low
      humidity conditions.

PMID- 16956276
TI  - Exposure of monomolecular lithographic patterns to ambient: an X-ray
      photoemission spectromicroscopy study.
AB  - Patterned self-assembled monolayers (SAMs) of alkanethiolates (AT) on Au and Ag
      substrates were imaged and characterized by scanning photoelectron microscopy
      (SPEM). The patterns were prepared in situ by direct writing with the zone-plate
      focused X-ray beam provided by the SPEM station. Whereas both AT/Au and AT/Ag
      behaved alike upon the irradiation, which resulted in similar contrasts in the
      fabricated patterns and similar microspot spectra from the irradiated areas, the
      intensity relationship between the patterned and nonpatterned areas changed by
      different pathways for the Au and Ag substrates after the exposure of the
      patterns to ambient. The SPEM data imply that weakly bound molecular fragments
      are desorbed from the irradiated areas upon air exposure in the case of Ag,
      whereas adsorption of airborne molecules from ambient occurs for the Au
      substrate. The origin of the observed differences is presumably related to the
      specific branching patterns of irradiation-induced modification of AT/Au and
      AT/Ag.

PMID- 16956277
TI  - Glass-liquid transition of carbon dioxide and its effect on water segregation.
AB  - The interactions between CO(2) and D(2)O molecules have been investigated by
      using time-of-flight secondary ion mass spectrometry in the temperature rage 13
      120 K. The monolayer of CO(2) tends to wet or intermix with the D(2)O film below
      40 K and dewets the surface above 60 K. The water nanoclusters deposited on the
      CO(2) multilayers also start to segregate at 50-60 K and are finally incorporated
      in the bulk at 85-90 K, where the morphology of the film changes abruptly
      together with the desorption rate of the CO(2) molecules. The break at 85 K
      should be caused by the occurrence of the fluidized film whereas the glass
      transition temperature of CO(2), as determined from the onset of translational
      molecular diffusion, is assigned to 50 K. This behavior may be related to the
      ultraviscous nature of the supercooled liquid, arising from the decoupling
      between the translational molecular diffusion and viscosity. The He(+)
      irradiation of the mixed CO(2)-D(2)O ice and the D(2)(+) irradiation of the CO(2)
      ice at 13 K do not yield any surface residues assignable to H(2)CO(3) and its
      precursors above 100 K. This result may be related to the segregation between the
      CO(2) and D(2)O molecules.

PMID- 16956278
TI  - Role of the adsorption phenomenon on the ionic equilibrium distribution and on
      the transient effects in electrolytic cells.
AB  - We analyze the influence of the adsorption of ions at the interfaces on the
      transient phenomena occurring in an electrolytic cell submitted to a steplike
      external voltage. In the limit of small amplitude of the applied voltage, where
      the equation of the problem can be linearized, we obtain an analytical solution
      for the bulk and surface densities of ions and for the electrical potential. We
      also obtain, in this limit, the relaxation time for the transient phenomena.

PMID- 16956279
TI  - Ti-containing mesoporous organosilica as a photocatalyst for selective olefin
      epoxidation.
AB  - We previously found that Ti-containing mesoporous silica (T-S) with isolated and
      tetrahedrally coordinated Ti-oxide species, when photoactivated in acetonitrile
      with molecular oxygen (O(2)), catalyzes highly selective epoxidation of olefins
      (Chem. Commun. 2005, 5977). The system showed the highest epoxide selectivity
      among the photocatalytic systems proposed so far, but showed insufficient olefin
      conversion. In the present work, we have employed Ti-containing mesoporous
      organosilicas (T-OS), synthesized by a surfactant-templating method with an
      organosilane precursor, as the photocatalyst and have studied the effects on the
      olefin conversion and the epoxide selectivity. The T-OS catalysts demonstrate the
      same high epoxide selectivity as does T-S, but scarcely improve the olefin
      conversion. Photoluminescence measurement reveals that the T-OS catalysts with
      high surface hydrophobicity enhance the access of hydrophobic olefins to the
      photoexcited Ti-oxide species as expected, but destabilize the excited species
      themselves. ESR analysis demonstrates that the T-OS catalysts also destabilize
      the active oxygen radical (O(3)(*-)), a crucial oxidant for olefin epoxidation,
      formed on the excited Ti-oxide species. These destabilizations counteract the
      enhanced olefin access to the excited species, resulting in almost no improvement
      in olefin conversion. Through detailed analyses, we have summarized the changes
      in photocatalytic properties of the Ti-oxide species, associated with the organic
      modification of the catalyst.

PMID- 16956280
TI  - Two-photon fluorescence spectroscopy of individually trapped pseudoisocyanine J
      aggregates in aqueous solution.
AB  - We have investigated a pseudoisocyanine dye aqueous solution including nanometer
      sized J-aggregates by combining optical trapping and two-photon fluorescence
      spectroscopy. By focusing an intense near-infrared laser into an 8 x 10(-3) M
      solution, the intense fluorescence from J-aggregates for a few to tens of seconds
      is observed intermittently, indicating that individual J-aggregates are trapped
      in and diffuse out from a focal spot. The peak position and full width at half
      maximum of the J-band are different from each other. By measuring 171 J
      aggregates, it was found that J-aggregates can be classified largely into two
      groups. The existence of two kinds of groups of J-aggregates could be attributed
      to the difference in the nucleation process, which is affected by the substrate.
      J-aggregates possessing a J-band of a narrower bandwidth in a shorter wavelength
      region are trapped for a longer period of time, indicating that highly ordered J
      aggregates are trapped for a longer period of time because of their high
      polarizability.

PMID- 16956281
TI  - Theoretical study on silver- and gold-loaded zeolite catalysts: thermodynamics
      and IR spectroscopy.
AB  - Density functional calculations have been carried out to determine geometries,
      adsorption energies and vibrational frequencies of NO, N(2)O, CO, O(2), and
      H(2)O, on a model for Ag(I) and Au(I) ion-exchanged ZSM-5 catalysts. Using
      statistical mechanics, the DeltaH and DeltaG values were calculated in order to
      evaluate the stability of the adsorbates on Ag(I) and Au(I) sites. The calculated
      vibrational frequencies are in reasonable agreement with the reported
      experimental values. The analysis of the results shows that at 475 degrees C the
      adsorption of two NO molecules and the direct N(2)O decomposition on AgZSM-5 are
      thermodynamically unfavorable. The adsorption of one NO molecule presents a small
      positive DeltaG value. On the contrary, in the case of AuZSM-5, the adsorption of
      one NO molecule and the direct N(2)O decomposition to produce N(2) are
      thermodynamically favorable. For both models, the N(2)O decomposition by AgO and
      AuO species is thermodynamically very favorable. The analysis of the interaction
      with H(2)O shows that water displaces the adsorbed NO on AgZSM-5 but not on AuZSM
      5 which indicates that the AuZSM-5 catalyst is less sensitive to deactivation by
      H(2)O than the AgZSM-5 catalyst.

PMID- 16956282
TI  - Local mechanical properties of plasma treated polystyrene surfaces.
AB  - We study how a local air plasma treatment affects the mechanical properties of
      polystyrene by performing indentation measurements on the polymer in the elastic
      and plastic regime. The local exposure to plasma was obtained by placing a shadow
      mask with quadratic holes of 45 x 45 microm(2) on top of the polymer substrate,
      providing uncovered (exposed to the plasma) and covered (protected from the
      plasma) areas. We have analyzed quantitatively the topography and the elastic
      plastic properties of such a sample with atomic force microscopy (AFM)
      measurements, both before and after plasma treatment. To enhance the differences
      between covered and uncovered areas, the sample has been exposed to solvent
      vapor. This generates regions which are differently swollen. The quantitative
      investigation of the mechanical properties of the swollen sample for different
      solvent exposure times gives further insight into the changes of polystyrene
      mechanical properties caused by the plasma.

PMID- 16956283
TI  - Structure effects of benzene hydrogenation studied with sum frequency generation
      vibrational spectroscopy and kinetics on Pt(111) and Pt(100) single-crystal
      surfaces.
AB  - Sum frequency generation (SFG) surface vibrational spectroscopy and kinetic
      measurements using gas chromatography have identified at least two reaction
      pathways for benzene hydrogenation on the Pt(100) and Pt(111) single-crystal
      surfaces at Torr pressures. Kinetic studies at low temperatures (310-370 K) show
      that benzene hydrogenation does not proceed through cyclohexene. A Langmuir
      Hinshelwood-type rate law for the low-temperature reaction pathway is identified.
      The rate-determining step for this pathway is the addition of the first hydrogen
      atom to adsorbed benzene for both single-crystal surfaces, which is verified by
      the spectroscopic observation of adsorbed benzene at low temperatures on both the
      Pt(100) and Pt(111) crystal faces. Low-temperature SFG studies reveal chemisorbed
      and physisorbed benzene on both surfaces. At higher temperatures (370-440 K),
      hydrogenation of benzene to pi-allyl c-C(6)H(9) is observed only on the Pt(100)
      surface. Previous single-crystal studies have identified pi-allyl c-C(6)H(9) as
      the rate-determining step for cyclohexene hydrogenation to cyclohexane.

PMID- 16956284
TI  - Surface-assisted transient displacement charge technique. I. Photoinduced charge
      transfer in self-assembled monolayers.
AB  - Surface-assisted photoinduced transient displacement charge (SPTDC) technique was
      developed in order to study light-induced charge transfer in surface-bound
      molecules and applied to investigation of self-assembled monolayers of 7
      diethylaminocoumarin and 2,4-dinitrophenylamine. The dipole moment change
      measured by SPTDC correlates reasonably well with that measured in solution by
      standard PTDC technique and with semiempirical calculations. Shortening of the
      excited-state lifetime of surface-immobilized coumarin due to stimulated emission
      was observed in both fluorescence and dipole measurements. The dipole signal
      decline in low-polarity solvents indicates the importance of dipole-dipole
      interaction that causes reorientation of molecules upon photoexcitation.

PMID- 16956285
TI  - Surface-assisted transient displacement charge technique. II. Effect of gases on
      photoinduced charge transfer in self-assembled monolayers.
AB  - Surface-assisted photoinduced transient displacement charge (SPTDC) technique was
      used to study charge transfer in self-assembled monolayers of 7
      diethylaminocoumarin covalently linked to an oxide surface in the atmosphere of
      different gases. The dipole signal was found to be opposite to that in solution
      and dependent on the nature of the gas and its pressure. The results were
      explained by collision-induced relaxation that impedes uninhibited tilting of
      molecules onto the surface. Collisions with paramagnetic oxygen induce
      intersystem crossing to long-lived triplet dipolar states of coumarin with the
      rate close to half of that for the collision rate.

PMID- 16956286
TI  - Rings and strain in pure silica zeolites.
AB  - The stability of rings in pure silica zeolite frameworks is investigated through
      a new method. The energetic terms influencing the stability of rings are
      evaluated through the short-range plus electrostatics corresponding to SiO bonds
      and OSiO and SiOSi angles. Several atomistic force fields have been evaluated,
      and a reparametrization of the Vessal-Leslie-Catlow force field has been chosen
      because of its physical meaning and good structural accuracy. The ring energetics
      are analyzed and discussed in terms of local strain in the framework and in terms
      of geometric variables. This methodology allows to differentiate between the
      strain of rings of a given size in different zeolite structures. In particular,
      it is found that double four rings (D4Rs) are not necessarily, as previously
      stated, a strained secondary building unit. The analyses of D4Rs in the
      topologies AST, BEC, and LTA allow the calculation of its stability in the
      different structures showing high energy in BEC and LTA and low energy in AST.
      Implications of these results on nucleation of zeolites are drawn regarding the
      facility with which D4Rs are inserted in different frameworks.

PMID- 16956287
TI  - Adsorption and assembly of copper phthalocyanine on cross-linked TiO2(110)-(1 x
      2) and TiO2(210).
AB  - Copper phthalocyanine (CuPc) on reconstructed rutile TiO(2) was studied with
      ultrahigh vacuum variable temperature scanning tunneling microscopy. On cross
      linked TiO(2)(110)-(1 x 2), the CuPc molecules at low coverages sparsely lay flat
      at the link sites and tilted in troughs between [001] rows. Increase of the CuPc
      coverage led to the trapping of the CuPc molecules by the rectangular surface
      cells fenced by the oxygen columns along the [001] direction and the cross-link
      rows. Each cell could trap one CuPc molecule at intermediate coverages and two
      CuPc molecules at higher coverages. On TiO(2)(210), the CuPc molecules tilted in
      defect-free areas and lay at defect sites with their molecular planes parallel to
      the substrate surface. Further increase of the CuPc coverage induced the
      formation of one- and two-dimensional assemblies on TiO(2)(210).

PMID- 16956288
TI  - Water dynamics in hardened ordinary Portland cement paste or concrete: from
      quasielastic neutron scattering.
AB  - Portland cement reacts with water to form an amorphous paste through a chemical
      reaction called hydration. In concrete the formation of pastes causes the mix to
      harden and gain strength to form a rock-like mass. Within this process lies the
      key to a remarkable peculiarity of concrete: it is plastic and soft when newly
      mixed, strong and durable when hardened. These qualities explain why one
      material, concrete, can build skyscrapers, bridges, sidewalks and superhighways,
      houses, and dams. The character of the concrete is determined by the quality of
      the paste. Creep and shrinkage of concrete specimens occur during the loss and
      gain of water from cement paste. To better understand the role of water in mature
      concrete, a series of quasielastic neutron scattering (QENS) experiments were
      carried out on cement pastes with water/cement ratio varying between 0.32 and
      0.6. The samples were cured for about 28 days in sealed containers so that the
      initial water content would not change. These experiments were carried out with
      an actual sample of Portland cement rather than with the components of cement
      studied by other workers. The QENS spectra differentiated between three different
      water interactions: water that was chemically bound into the cement paste, the
      physically bound or "glassy water" that interacted with the surface of the gel
      pores in the paste, and unbound water molecules that are confined within the
      larger capillary pores of cement paste. The dynamics of the "glassy" and "unboud"
      water in an extended time scale, from a hundred picoseconds to a few nanoseconds,
      could be clearly differentiated from the data. While the observed motions on the
      picosecond time scale are mainly stochastic reorientations of the water
      molecules, the dynamics observed on the nanosecond range can be attributed to
      long-range diffusion. Diffusive motion was characterized by diffusion constants
      in the range of (0.6-2) 10(-9) m(2)/s, with significant reduction compared to the
      rate of diffusion for bulk water. This reduction of the water diffusion is
      discussed in terms of the interaction of the water with the calcium silicate gel
      and the ions present in the pore water.

PMID- 16956289
TI  - Reactivity of gas barrier membranes filled with reactive particulates.
AB  - Gas barrier plastic films and structures capable of removing a permeating solute
      via irreversible chemical reactions in the polymer matrix are investigated in
      applications of active packaging for controlling contained environments. To
      significantly reduce permeation rates through such active barriers, high barrier
      reactivity is required. When the reactive species take the form of fine
      particulates sparingly dispersed in the matrix, the reactivity of a composite
      membrane is affected by a lower frequency of collisions of dissolved gas
      molecules with the distributed reactive particles. The mean size of the particles
      and their volume fraction in the matrix are identified as the critical factors
      affecting the overall reactivity of uniformly filled composite barriers. A two
      scale coarse-grained model of reaction-diffusion in a matrix is developed by
      introducing a unit cell approach to estimate the reaction rate upon collision
      with the particles and by choosing the unit length of diffusive molecular
      displacement equal to the mean diameter of the reactive particles to describe
      diffusion across the barrier and statistics of molecule-particle collisions. The
      corresponding method for evaluating the barrier reactivity is described. The
      effects of the system parameters on the effective gas transport rates across the
      reactive composite barriers including polymer nanocomposite barriers with
      reactive additives are quantified.

PMID- 16956290
TI  - Transport in amorphous solid water films: implications for self-diffusivity.
AB  - Thermal desorption spectroscopy is employed to examine transport mechanisms in
      structured, nanoscale films consisting of labeled amorphous solid water (ASW,
      H(2)(18)O, H(2)(16)O) and organic spacer layers (CCl(4), CHCl(3)) prior to ASW
      crystallization (T approximately 150-160 K). Self-transport is studied as a
      function of both the ASW layer and the organic spacer layer film thickness, and
      the effectiveness of these spacer layers as a bulk diffusion "barrier" is also
      investigated. Isothermal desorption measurements of structured films are combined
      with gas uptake measurements (CClF(2)H) to investigate water self-transport and
      changes in ASW film morphology during crystallization and annealing. CCl(4)
      desorption is employed as a means to investigate the effects of ASW film
      thickness and heating schedule on vapor-phase transport. Combined, these results
      demonstrate that the interlayer mixing observed near T approximately 150-160 K is
      inconsistent with a mechanism involving diffusion through a dense phase; rather,
      we propose that intermixing occurs via vapor-phase transport through an
      interconnected network of cracks/fractures created within the ASW film during
      crystallization. Consequently, the self-diffusivity of ASW prior to
      crystallization (T approximately 150-160 K) is significantly smaller than that
      expected for a "fragile" liquid, indicating that water undergoes either a glass
      transition or a fragile-to-strong transition at a temperature above 160 K.

PMID- 16956291
TI  - Platinum nanofilm formation by EC-ALE via redox replacement of UPD copper:
      studies using in-situ scanning tunneling microscopy.
AB  - The growth of Pt nanofilms on well-defined Au(111) electrode surfaces, using
      electrochemical atomic layer epitaxy (EC-ALE), is described here. EC-ALE is a
      deposition method based on surface-limited reactions. This report describes the
      first use of surface-limited redox replacement reactions (SLR(3)) in an EC-ALE
      cycle to form atomically ordered metal nanofilms. The SLR(3) consisted of the
      underpotential deposition (UPD) of a copper atomic layer, subsequently replaced
      by Pt at open circuit, in a Pt cation solution. This SLR(3) was then used a
      cycle, repeated to grow thicker Pt films. Deposits were studied using a
      combination of electrochemistry (EC), in-situ scanning tunneling microscopy (STM)
      using an electrochemical flow cell, and ultrahigh vacuum (UHV) surface studies
      combined with electrochemistry (UHV-EC). A single redox replacement of upd Cu
      from a PtCl(4)(2-) solution yielded an incomplete monolayer, though no
      preferential deposition was observed at step edges. Use of an iodine adlayer, as
      a surfactant, facilitated the growth of uniformed films. In-situ STM images
      revealed ordered Au(111)-(square root 3 x square root 3)R30 degrees-iodine
      structure, with areas partially distorted by Pt nanoislands. After the second
      application, an ordered Moire pattern was observed with a spacing consistent with
      the lattice mismatch between a Pt monolayer and the Au(111) substrate. After
      application of three or more cycles, a new adlattice, a (3 x 3)-iodine structure,
      was observed, previously observed for I atoms adsorbed on Pt(111). In addition,
      five atom adsorbed Pt-I complexes randomly decorated the surface and showed some
      mobility. These pinwheels, planar PtI(4) complexes, and the ordered (3 x 3)
      iodine layer all appeared stable during rinsing with blank solution, free of I(-)
      and the Pt complex (PtCl(4)(2-)).

PMID- 16956292
TI  - Density functional theory study of ligand binding on CdSe (0001), (0001), and
      (1120) single crystal relaxed and reconstructed surfaces: implications for
      nanocrystalline growth.
AB  - To gain a better understanding of the influence of ligand-surface interactions on
      nanocrystalline growth, periodic density functional theory calculations were
      employed in the study of the binding of organic ligands on the relaxed nonpolar
      (1120) and polar Se terminated (0001) surfaces and the relaxed and vacancy and
      adatom reconstructed Cd terminated (0001) surface. We examined chemisorption
      properties of phosphine, amine, phosphine oxide, carboxylic acid, and phosphinic
      acid model ligands, including preferred binding sites and geometries, vibrational
      frequencies, and binding energetics, and compared findings to intrinsic growth
      via addition of CdSe molecules or Cd and Se atoms. Our results indicate that
      binding of the ligands is preferred in the electron-poor 1-fold sites on all
      surfaces, with secondary coordination of the acidic ligands through the hydroxyl
      hydrogen to the electron-rich surface sites. In general ligand adsorption
      directly obstructs binding sites for growth species on the (1120) surface and
      only indirectly on the two polar surfaces. The order of binding affinities on the
      (1120) and (0001) surfaces is PH(3) < OPH(3) approximately HCOOH < NH(3) <
      OPH(2)OH and that on the (0001) surface is OPH(3) approximately HCOOH < OPH(2)OH
      < NH(3) < PH(3). Our findings corroborate the experimental observation that
      incorporation of the nonbulky phosphinic acid-type ligands with high affinity and
      high selectivity for both the (1120) and (0001) surfaces strongly enhances
      unidirectional growth on the (0001) surface, while incorporation of either bulky
      ligands or ligands with moderate affinity does not. Higher affinity of all
      traditionally used ligands for the (1120) surface compared to the (0001) surface
      also suggests that new ligands should be engineered to achieve the synthesis of
      novel shapes that require preferential growth on the (1120) surface.

PMID- 16956293
TI  - Comparison of hydrogen bonding in 1-octanol and 2-octanol as probed by
      spectroscopic techniques.
AB  - Liquid 1-octanol and 2-octanol have been investigated by infrared (IR), Raman,
      and Brillouin experiments in the 10-90 degrees C temperature range. Self
      association properties of the neat liquids are described in terms of a three
      state model in which OH oscillators differently implicated in the formation of H
      bonds are considered. The results are in quantitative agreement with recent
      computational studies for 1-octanol. The H-bond probability is obtained by Raman
      data, and a stochastic model of H-bonded chains gives a consistent picture of the
      self-association characteristics. Average values of hydrogen bond enthalpy and
      entropy are evaluated. The H-bond formation enthalpy is ca. -22 kJ/mol and is
      slightly dependent on the structural isomerism. The different degree of self
      association for the two octanols is attributed to entropic factors. The more
      shielded 2-isomer forms larger fractions of smaller, less cooperative, and more
      ordered clusters, likely corresponding to cyclic structures. Signatures of a
      different cluster organization are also evidenced by comparing the H-bond energy
      dispersion (HBED) of OH stretching IR bands. A limiting cooperative H-bond
      enthalpy value of 27 kJ/mol is found. It is also proposed that the different H
      bonding capabilities may modulate the extent of interaggregate hydrocarbon
      interactions, which is important in explaining the differences in molar volume,
      compressibility, and vaporization enthalpy for the two isomers.

PMID- 16956294
TI  - Molecular simulation study of some thermophysical and transport properties of
      triazolium-based ionic liquids.
AB  - Results of a molecular dynamics study of several triazolium-based ionic liquids
      are reported. Triazolium cations include 1,2,4-triazolium, 1,2,3-triazolium, 4
      amino-1,2,4-triazolium, and 1-methyl-4-amino-1,2,4-triazolium. Each cation was
      paired with a nitrate or perchlorate anion. These materials are part of a class
      of ionic compounds that have been synthesized recently but for which little
      physical property data are available. Properties of the more common ionic liquid,
      1-n-butyl-3-methylimidazolium nitrate, are also computed and compared with the
      properties of the triazolium-based compounds. A molecular mechanics force field
      was developed for these materials using a mix of ab initio calculations and
      parameter fitting using the molecular compound 1H-1,2,4-triazole as a basis for
      the triazolium cations. Liquid-phase properties that were computed include heat
      capacities, cohesive energy densities, gravimetric densities/molar volumes as a
      function of temperature and pressure, self-diffusivities, rotational time
      constants, and various pair correlation functions. In the solid phase, heat
      capacities and lattice parameters were computed. Of all of these properties, only
      lattice parameters have been measured experimentally (and only for four of the
      triazolium compounds). The agreement with the experimental crystal structures was
      good. When compared with that of the imidazolium-based ionic liquid, the
      triazolium-based materials have much smaller molar volumes, higher cohesive
      energy densities, and larger specific heat capacities. They also tend to be less
      compressible, have a higher gravimetric density, and have faster rotational
      dynamics but similar translational dynamics.

PMID- 16956295
TI  - Alzheimer amyloid beta(1-40) peptide: interactions with cationic gemini and
      single-chain surfactants.
AB  - The aggregation of amyloid beta-peptide [Abeta(1-40)] into fibril is a key
      pathological process associated with Alzheimer's disease. The effect of cationic
      gemini surfactant hexamethylene-1,6-bis-(dodecyldimethylammonium bromide)
      [C(12)H(25)(CH(3))(2)N(CH(2))(6)N(CH(3))(2)C(12)H(25)]Br(2) (designated as
      C(12)C(6)C(12)Br(2)) and single-chain cationic surfactant
      dodecyltrimethylammonium bromide (DTAB) on the Alzheimer amyloid beta-peptide
      Abeta(1-40) aggregation behavior was studied by microcalorimetry, circular
      dichroism (CD), and atomic force microscopy (AFM) measurements at pH 7.4. Without
      addition of surfactant, 0.5 g/L Abeta(1-40) mainly exists in dimeric state. It is
      found that the addition of the monomers of C(12)C(6)C(12)Br(2) and DTAB may cause
      the rapid aggregation of Abeta(1-40) and the fibrillar structures are observed by
      CD spectra and the AFM images. Due to the repulsive interaction among the head
      groups of surfactants and the formation of a small hydrophobic cluster of
      surfactant molecules, the fibrillar structure is disrupted again as the
      surfactant monomer concentration is increased, whereas globular species are
      observed in the presence of micellar solution. Different from single-chain
      surfactant, C(12)C(6)C(12)Br(2) has a much stronger interaction with Abeta(1-40)
      to generate larger endothermic energy at much lower surfactant concentration and
      has much stronger ability to induce the aggregation of Abeta(1-40).

PMID- 16956296
TI  - Generalized two-dimensional correlation analysis of NMR and Raman spectra for
      structural evolution characterizations of silk fibroin.
AB  - Generalized two-dimensional (2D) correlation spectroscopy was used to
      characterize the structural evolution of silk fibroin as the pH changed from 6.8
      to 4.8, demonstrating that the conformational transitions of silk fibroin are
      induced step by step as the pH decreases. 2D homo- and hetero-spectral
      correlation spectroscopy was used to establish the relationship between
      information extracted from NMR and Raman spectroscopy. This novel method reveals
      the structural evolution using two probes with different frequency scales (10(5
      9) Hz for nuclear spin motion and 10(12-14) Hz for molecular vibration motion),
      reflecting the different spatial scale sensitivity to the molecular
      conformational change. The transition order is identified as silk I state (helix
      dominant) --> silk I intermediate state --> silk II intermediate state --> silk
      II state (beta-sheet dominant), as the pH decreases. The results may rationalize
      the silkworm spinning process, which undergoes the conformational transition
      steadily from the soluble helix state to the insoluble beta-sheet state as the pH
      decreases from the posterior to anterior glands.

PMID- 16956297
TI  - Investigation of the catalytic mechanism of farnesyl pyrophosphate synthase by
      computer simulation.
AB  - Farnesyl pyrophosphate synthase (FPPS) catalyses the formation of a key cellular
      intermediate in isoprenoid metabolic pathways, farnesyl pyrophosphate, by the
      sequential head-to-tail condensation of two molecules of isopentenyl diphosphate
      (IPP) with dimethylallyl diphosphate (DMAPP). Recently, FPPS has been shown to
      represent an important target for the treatment of parasitic diseases such as
      Chagas disease and African trypanosomiasis. Bisphosphonates, pyrophosphate
      analogues in which the oxygen bridge between the two phosphorus atoms has been
      replaced by a carbon substituted with different side chains, are able to inhibit
      the FPPS enzyme. Moreover, nitrogen-containing bisphosphonates have been proposed
      as carbocation transition state analogues of FPPS. On the basis of structural and
      kinetic data, different catalytic mechanisms have been proposed for FPPS. By
      analyzing different reaction coordinates we propose that the reaction occurs in
      one step through a carbocationic transition state and the subsequent transfer of
      a hydrogen atom from IPP to the pyrophosphate moiety of DMAPP. Moreover, we have
      analyzed the role of the active site amino acids on the activation barrier and
      the reaction mechanism. The structure of the active site is well conserved in the
      isoprenyl diphosphate synthase family; thus, our results are relevant for the
      understanding of this important class of enzymes and for the design of more
      potent and specific inhibitors for the treatment of parasitic diseases.

PMID- 16956298
TI  - Low-frequency cooperative dynamics in L-, D-, and DL-alanine crystals: a 13C and
      15N cross-polarization magic-angle-spinning NMR study.
AB  - Knowledge of the dynamical changes in molecular configurations in various amino
      acid structures over a wide range of time scales is important since such changes
      may influence the structural transformations and the diverse biological
      functionalities of proteins. Using the temperature dependence of the rotating
      frame NMR spin-lattice relaxation times T(1rho) of protons as a probe, we have
      investigated the low-frequency (approximately 60-100 kHz) dynamics in the crystal
      structures of L-, D-, and DL- alanine (C(12)H(28)O(8)N(4)) polymorphs. The proton
      relaxation times T(1rho) were obtained from (13)C <-- (1)H and (15)N <-- (1)H
      cross-polarization magic-angle-spinning NMR experiments over a temperature range
      of 192-342 K. The data reveal that the time scales of these low-frequency
      dynamical processes are distinctly different from the localized, high-frequency
      rotational motion of methyl and amine groups. The strongly asymmetric T(1rho)
      versus temperature curves and the subtle dynamical differences between the DL
      alanine and the L- and d-enantiomorphs indicate that these low-frequency
      processes are cooperative in nature and are sensitive to molecular packing.

PMID- 16956299
TI  - Solvent effects on the low-lying excited states of a model of retinal.
AB  - The low-lying excited states of a solution in alcohol of a five-double-bond model
      of the rhodopsin protein chromophore, the protonated 11-cis-retinal Schiff base
      (PSB11), are studied theoretically. We combine a multireference perturbational
      treatment in the description of the solute molecule with molecular dynamics
      calculations in the description of the solvent. The geometry, charge
      distribution, and electronic spectra are strongly influenced by the solvent. The
      solvent shift values show a marked dependence on the use of relaxed geometries in
      solution and on the nature of the states involved in the excitation process. The
      dynamic correlation has a strong effect on the order of the excited states. In
      solution, the first two excited states almost become degenerate.

PMID- 16956302
TI  - Immunosuppressive preconditioning or induction regimens : evidence to date.
AB  - The success of solid organ transplantation has been directly related to the
      development of immunosuppressive drug therapies. Preconditioning or induction
      therapy was developed to reduce early immunological and nonimmunological renal
      injury, with the goal of increasing long-term graft survival. However, the
      routine induction of immunological tolerance to solid organ allograft is
      currently not achievable because of the morbidity and mortality related to the
      immunosuppressive regimens themselves. The different therapeutic preconditioning
      or induction agents and their associated effects on cellular rejection, graft
      survival outcomes and the need for multiagent post-transplant maintenance therapy
      are reviewed.

PMID- 16956303
TI  - Pathophysiology, clinical presentation and treatment of gout.
AB  - Gout is a common form of inflammatory arthritis that has been managed primarily
      in general medical practices for centuries. It appears that there has been an
      increasing prevalence of gout over the past decades, implying a growing public
      health burden. Accurate diagnosis and recognition of the various stages and
      manifestations of gout enable realistic goal setting for management. Recent
      evidence suggests new risk factors and potentially refutes others. Management of
      gout requires characterising and modifying risk factors and associated disorders,
      and commonly initiating drug therapy. Pharmacotherapy of gout includes the
      management of acute flares with anti-inflammatory agents such as NSAIDs and
      glucocorticoids and long-term treatment with urate-lowering drugs. Although
      pharmacotherapy is generally safe and effective, there are caveats and
      limitations to all gout therapies. Patient non-adherence and errors with the use
      of drugs for gout treatment are important factors leading to medical failures.
      With early intervention, careful monitoring and patient education, gout is a
      condition that can be managed very effectively. The advent of new drugs (such as
      febuxostat and urate oxidase [uricase]) and enhanced understanding of the
      pathogenesis of gout continue to improve our therapeutic options, particularly in
      a subset of patients with refractory disease and those who are intolerant to
      currently available medications.

PMID- 16956304
TI  - Recent developments in the treatment of otitis media with effusion.
AB  - The management of otitis media with effusion (OME) has received much attention
      recently as a result of, among other factors, the development of resistant
      bacteria and the finding of less long-term impact of middle-ear effusion (MEE) on
      development than previously believed. Guidelines have recently been published for
      the management of OME promoting more accurate diagnosis, particularly
      distinguishing acute otitis media from OME, and recommending the 'judicious' use
      of antibacterials. Today, more emphasis is being placed on prevention of disease
      by reducing risk factors and the development of vaccines. The identification of
      susceptibility genes may lead to better understanding of the pathogenesis of
      otitis media, which in turn may lead to the development of more innovative and
      satisfactory methods for prevention and treatment.

PMID- 16956306
TI  - Intravenous ibandronate: in the treatment of osteoporosis.
AB  - Ibandronate (ibandronic acid) is a potent nitrogen-containing bisphosphonate that
      inhibits osteoclast-mediated bone resorption in women with postmenopausal
      osteoporosis. Recently, an intravenous (IV) formulation of ibandronate for
      intermittent injection, which circumvents the fasting and posture requirements
      associated with administration of oral bisphosphonates, was approved for use in
      this patient population. In initial placebo-controlled studies of 1 year's
      duration, IV ibandronate (< or =2mg once every 3 months) increased lumbar spine
      bone mineral density (BMD) and reduced levels of biochemical markers of bone
      turnover in a dose-dependent manner. Dosages < or =1mg every 3 months were found
      to be suboptimal in terms of fracture prevention in a 3-year trial. Subsequently,
      the large randomised, double-blind, noninferiority DIVA trial showed that, in
      terms of increasing lumbar spine BMD (primary endpoint), IV ibandronate 3mg once
      every 3 months and 2mg once every 2 months for 1 year were noninferior and also
      superior to oral ibandronate 2.5mg once daily, a regimen with proven antifracture
      efficacy. Median reductions from baseline in biochemical markers of bone turnover
      were similar for the IV and oral regimens. IV ibandronate was generally well
      tolerated in clinical trials. Treatment-related adverse events included
      musculoskeletal events and transient influenza-like symptoms, the latter mainly
      associated with the first dose.

PMID- 16956305
TI  - Monoclonal antibody-based targeted therapy in breast cancer: current status and
      future directions.
AB  - The recent development of monoclonal antibodies targeting growth factor receptors
      in cancer treatment represents a milestone for both researchers and physicians.
      Advances in the understanding of key molecular pathways for tumour growth and
      survival have facilitated the development of these targeted therapies, in
      particular in breast cancer. This review focuses on the three most important
      recombinant humanised monoclonal antibodies that have shown activity in women
      with breast cancer: trastuzumab, pertuzumab and bevacizumab. Trastuzumab, an anti
      erbB2 (human epidermal growth factor receptor) monoclonal antibody, is currently
      routinely used in both the metastatic and adjuvant settings for patients with
      erbB2-positive tumours. Pertuzumab, a monoclonal antibody binding to a different
      epitope on erbB2 than trastuzumab, is under early clinical evaluation. This drug
      has been developed for breast cancer patients, whether overexpressing erbB2 or
      not. Bevacizumab, a monoclonal antibody directed against vascular endothelial
      growth factor-A, is being evaluated in the metastatic setting for its
      antiangiogenic properties, and is showing promising results.

PMID- 16956310
TI  - Entecavir: a review of its use in chronic hepatitis B.
AB  - Entecavir (Baraclude) is a novel nucleoside analogue of 2'-deoxyguanosine whose
      intracellular triphosphate form inhibits replication of the hepatitis B virus
      (HBV). In large, randomised, double-blind, phase III clinical trials in patients
      with chronic HBV infection, oral entecavir 0.5 or 1.0mg once daily for up to 96
      weeks was superior to lamivudine 100 mg/day in improving hepatic histology,
      normalising aminotransferase levels and suppressing viraemia to levels
      undetectable by polymerase chain reaction (PCR) assay in nucleoside-naive
      hepatitis B e antigen (HBeAg)-negative (precore or core promoter mutants) and/or
      HBeAg-positive patients, and in lamivudine-refractory (persistent viraemia during
      lamivudine therapy) HBeAg-positive patients. In addition, the tolerability
      profile of entecavir was generally similar to that of lamivudine. Thus, entecavir
      is a primary option in the treatment of chronic HBV infection in both nucleoside
      naive and lamivudine-refractory patients.

PMID- 16956315
TI  - Environmental enrichment alters the behavioral profile of ratsnakes (Elaphe).
AB  - This study investigated the effects of environmentally enriched and standard
      laboratory housing conditions on behavioral performance in 16 subadult ratsnakes
      (Elaphe obsoleta) using a split-clutch design. In a problem-solving task, snakes
      housed in enriched environments (EC) exhibited shorter latencies to the goal hole
      as compared to snakes housed in standard conditions (SC). In an open field task,
      EC snakes tended to habituate more quickly than SC snakes with repeated testing.
      A feeding task did not reveal any significant differences between EC and SC
      snakes. A discriminant function analysis correctly assigned all snakes to their
      appropriate housing treatment groups, based on the responses in each of the
      behavioral tasks. This suggests that each group had a distinct behavioral
      profile; that is, EC snakes were more behaviorally adaptive than SC snakes. This
      study demonstrated that housing conditions can affect the behavior of captive
      snakes and produce improvements in behavior similar to those seen in mammalian
      enrichment studies.

PMID- 16956314
TI  - Using participatory rural appraisal (PRA) in the identification of children with
      disabilities in rural Kilifi, Kenya.
AB  - INTRODUCTION: Cross-sectional surveys have been used widely for identifying
      children with disabilities, but they have several disadvantages. The surveys
      concentrate on identifying impairments and do not encourage the participation and
      ownership of the community. Participatory rural appraisal (PRA) provides a cost
      effective and efficient method that reflects the local perceptions of disability
      and involves local people. These factors are important for sustainability in
      resource-poor countries. PURPOSE: To evaluate the application of PRA to
      identifying children with disabilities in a rural setting. METHODS: PRA was used
      to identify children with disabilities in two rural sub-locations in Kilifi,
      Kenya. Data were collected through 12 focus group discussions and 12 social
      mapping activities. A purposive convenience sample of teachers, village leaders
      and women groups participated in the PRA. The perceptions of disability were
      established before identification of the children. The categories of
      identification were based on these local perceptions. The qualitative data were
      analyzed thematically and validation was performed through triangulation.
      RESULTS: Disability was perceived locally as the existence of impairments,
      activity limitations and participation restrictions. Disabilities were associated
      with traditional beliefs including witchcraft, evil spirits and punishments from
      God. In some cases these categories were mutually exclusive and in others they
      were concurrent. Children who had lost their parents and were not being cared for
      by relatives (disadvantaged orphans) were also perceived as disabled children by
      teachers and local women, but not by community leaders. CONCLUSION: The results
      suggest that PRA is an efficient and cost-effective method of identifying
      children with disabilities according to local perceptions, and it may be useful
      in community-based rehabilitation as an alternative to surveys.

PMID- 16956313
TI  - Orlistat: a review of its use in the management of obesity.
AB  - Orlistat (Xenical) is a reversible inhibitor of gastric and pancreatic lipases.
      In conjunction with a hypocaloric diet and moderate exercise, orlistat is an
      effective drug for use in the management of obesity in adults with or without
      comorbidities. Recent data have shown that orlistat is also effective as a
      component of weight management strategies in obese adolescents. In addition to
      its well established efficacy in achieving modest weight loss, orlistat has been
      shown to improve glycaemic parameters in obese adults with type 2 diabetes
      mellitus as well as some features of the metabolic syndrome. Orlistat is
      generally well tolerated. Thus, orlistat is an option for the treatment of obese
      patients with or without type 2 diabetes and also has a role in the management of
      obese patients with the metabolic syndrome, associated comorbidities or
      concomitant disorders.

PMID- 16956316
TI  - Effects of three food enrichment items on the behavior of black lemurs (Eulemur
      macaco macaco) and Ringtail Lemurs (Lemur catta) at the Henson Robinson Zoo,
      Springfield, Illinois.
AB  - This study tested 3 food enrichment items mentioned in a laboratory primate
      newsletter with 6 adult Eulemur macaco and 3 adult Lemur catta to examine whether
      the items would affect the behavior of the lemurs. The results suggest that Food
      Enrichment Item 3 (a wire box filled with whole grapes, apples, or both hidden in
      straw hung from a branch within the enclosure) caused a significant decrease in
      the incidence of resting and a significant increase in the incidences of playing
      and grooming, with no significant effect on the incidence of feeding or foraging.
      The lemurs' behavior appeared to be most affected by the food enrichment item
      that required the most manipulation, closely followed by an enrichment that
      required a moderate amount of manipulation. The order of the exposure to the food
      enrichment items and the day of the week appear to have an attenuation effect on
      these behaviors and did affect the incidence of 3 stereotypic behaviors exhibited
      by a male L. catta such that 3 behaviors declined in occurrence as the study
      progressed.

PMID- 16956317
TI  - Description and evaluation of a canine volunteer blood donor program.
AB  - Human volunteer blood donor programs are commonplace, but the concept of nonhuman
      animal blood banking is relatively new. Few studies exist regarding efficacy,
      donor screening, and safety for volunteer companion animals. This retrospective
      study evaluated a nonprofit, community-based canine volunteer donor program using
      community blood drives. Of 98 potential donors, 14 were ineligible to donate,
      including 4 who tested seropositive for blood-borne pathogens. Of 84 donors, 45
      were Dog Erythrocyte Antigen (DEA) 1.1 positive and 39 were DEA1.1 negative.
      Donations totaling 143 included 29 repeat donors (35%). No serious adverse events
      occurred. Minor adverse events included acute donor reaction (2.8%), hematoma
      (4.2%), rebleeding (2.1%), and skin irritation (0.7%). Adverse event rates were
      comparable to data for human blood donations. A substantial fraction of donors
      donated multiple times, suggesting that volunteer donors and their guardians
      perceived the donation process to be safe and effective. This article discusses
      the issue of donor consent and use of the term volunteer. This study indicates
      that nonprofit, community-based canine volunteer donor programs for animal blood
      banks can be successful while maintaining high safety standards and ethical
      treatment of volunteers.

PMID- 16956318
TI  - Outcome of cats adopted from a biomedical research program.
AB  - Adoption of companion animals retired from biomedical research projects can
      provide an alternative, humane method for their disposition. For more than a
      decade, the University of Florida College of Veterinary Medicine has allowed
      investigators to arrange for the adoption of nonhuman animals used in their
      research. This report directed a survey to caregivers (owners) of 458 cats
      adopted over a 6-year period. The survey determined (a) retention rate of adopted
      cats in their original homes, (b) characteristics of adopters and cats, (c)
      adopters' initial expectations and subsequent experiences with the cats, (d)
      quality of the humananimal bond, and (e) adopters' perceptions of the adoption
      process. Completed surveys totaled 275 (60.0% response rate) with a median follow
      up interval of 38 months. Of cats surveyed, 91.3% were still in their original
      homes, 91.0% had seen a veterinarian following adoption, and 80.4% were highly
      valued family members. The procedures followed to place cats in appropriate homes
      satisfied the vast majority of adopters surveyed. These results suggest that
      adoption into private homes is a viable alternative for cats who have completed
      research studies.

PMID- 16956319
TI  - Physiological arousal for companion dogs working with their owners in animal
      assisted activities and animal-assisted therapy.
AB  - This study investigated the physiological reactions of companion dogs (Canis
      familiaris) used in animal-assisted activities and animal-assisted therapy by
      measuring salivary cortisol concentrations. The dog caregivers (owners) collected
      saliva samples (a) at 3 control days without therapeutic work, (b) directly
      before and after each therapeutic session during 3 consecutive months, and (c)
      again at 3 control days without therapeutic work. The study used an enzyme
      immunoassay to analyze the samples. Cortisol concentrations were significantly
      higher during therapy days than on control days. Dogs working during the first
      half of the day produced higher cortisol concentrations after therapeutic
      sessions than before, whereas dogs working in the afternoon produced lower
      cortisol concentrations. Cortisol concentrations were higher in short sessions
      than in long ones and increased relative to the number of therapeutic sessions
      done during the sampling period. The results indicate that therapeutic work was
      physiologically arousing for the dogs in this study. Whether these physiological
      responses are indicative of potentially negative stress or of positive excitement
      remains an open question.

PMID- 16956323
TI  - Biodiversity informatics.
AB  - Biodiversity informatics is an emerging field that applies information management
      tools to the management and analysis of species-occurrence, taxonomic character,
      and image data. A wide and growing range of tools is available for both curators
      and researchers. The development and implementation of formal data exchange
      standards and query protocols have made it possible to integrate data holdings
      from collections around the world. The current technological environment is
      summarized; protocols, standards, and tools for data management, sharing, and
      integration are reviewed; and methods and tools for analyzing species-occurrence
      and character data are examined. Direct access to primary data and imagery has
      the power to transform the means by which taxonomy is practiced and its results
      disseminated to the general community.

PMID- 16956324
TI  - IOP1, a novel hydrogenase-like protein that modulates hypoxia-inducible factor
      1alpha activity.
AB  - A central means by which mammalian cells respond to low oxygen tension is through
      the activation of the transcription factor HIF-1 (hypoxia-inducible factor-1).
      Under normoxic conditions, HIF-1alpha (the alpha subunit of HIF-1) is targeted
      for rapid degradation by the ubiquitin-proteasome pathway. Under hypoxic
      conditions, this degradation is inhibited, thereby leading to the stabilization
      and activation of HIF-1alpha. Here, we report the identification of IOP1 (iron
      only hydrogenase-like protein 1), a protein homologous with enzymes present in
      anaerobic organisms that contain a distinctive iron-sulfur cluster. IOP1 is
      present in a broad range of cell types. Knockdown of IOP1 using siRNA (small
      interfering RNA) in mammalian cells increases protein levels of HIF-1alpha under
      both normoxic and hypoxic conditions, and augments hypoxia-induced HRE (hypoxia
      response element) reporter gene and endogenous HIF-1alpha target gene
      expressions. We find that IOP1 knockdown up-regulates HIF-1alpha mRNA levels,
      thereby providing a mechanism by which knockdown induces the observed effects.
      The results collectively provide evidence that IOP1 is a component of the protein
      network that regulates HIF-1alpha in mammalian cells.

PMID- 16956325
TI  - Stabilizing daily clock proteins.
AB  - Biological timekeeping is determined by internal temporal programmes and the
      resetting of these programmes or clocks by external stimuli. Many of the core
      genes of the mammalian daily or circadian clock are known, but the factors
      regulating so-called 'clock' gene proteins are unclear. In this issue of the
      Biochemical Journal, Gallego and colleagues show for the first time that protein
      phosphatase 1 plays a major role in the stability of mammalian PER2, a key
      protein in the core clock works. This contrasts somewhat with circadian rhythm
      control in the fruitfly Drosophila and the fungus Neurospora where current
      evidence supports a role for protein phosphatase 2A in core timekeeping. The
      mechanisms underpinning these actions of phosphatase 1 are unclear, and future
      investigations will need to identify the regulatory subunit that targets
      phosphatase 1 to mammalian PER2 (Period 2).

PMID- 16956328
TI  - Open or laparoscopic colposuspension for stress incontinence: new evidence too
      late?

PMID- 16956329
TI  - Acute postpartum uterine inversion with haemorrhagic shock.

PMID- 16956326
TI  - Cell-penetrating peptides and antimicrobial peptides: how different are they?
AB  - Some cationic peptides, referred to as CPPs (cell-penetrating peptides), have the
      ability to translocate across biological membranes in a non-disruptive way and to
      overcome the impermeable nature of the cell membrane. They have been successfully
      used for drug delivery into mammalian cells; however, there is no consensus about
      the mechanism of cellular uptake. Both endocytic and non-endocytic pathways are
      supported by experimental evidence. The observation that some AMPs (antimicrobial
      peptides) can enter host cells without damaging their cytoplasmic membrane, as
      well as kill pathogenic agents, has also attracted attention. The capacity to
      translocate across the cell membrane has been reported for some of these AMPs.
      Like CPPs, AMPs are short and cationic sequences with a high affinity for
      membranes. Similarities between CPPs and AMPs prompted us to question if these
      two classes of peptides really belong to unrelated families. In this Review, a
      critical comparison of the mechanisms that underlie cellular uptake is
      undertaken. A reflection and a new perspective about CPPs and AMPs are presented.

PMID- 16956330
TI  - Time to re-visit the role of haemodynamic monitoring in obstetrics?

PMID- 16956331
TI  - Laparoscopic versus open Burch colposuspension: a randomised controlled trial.
AB  - OBJECTIVE: To compare perioperative characteristics, short-term, and long-term
      outcomes for laparoscopic Burch colposuspension (LBC) and open Burch
      colposuspension (OBC) for the treatment of urinary stress incontinence. DESIGN:
      Randomised surgical trial with single blinding. SETTING: Three tertiary level
      teaching hospitals involving seven surgeons of varying skill levels. POPULATION:
      Two hundred women with urodynamic stress incontinence (USI). METHODS: The two
      groups were treated in identical fashion, except for the laparoscopic or open
      approach to surgery. Attempts were made to blind the subjects and the observers
      obtaining outcome data to treatment group. Analyses were adjusted for surgeon
      experience. MAIN OUTCOME MEASURES: Absence of USI 6 months following surgery,
      postoperative pain, time spent in hospital, and time to return to activities of
      normal daily living. RESULTS: There were no significant differences in objective
      and subjective measures of cure and in patient satisfaction at 6 months, 24
      months, or 3-5 years of follow up between laparoscopic and open colposuspension
      groups. Laparoscopic colposuspension took longer time to perform (87 versus 42
      minutes, P< 0.0001) but was associated with less blood loss (P = 0.03), less pain
      (P = 0.02), and quicker return to normal activities (P = 0.01). CONCLUSION: LBC
      has significant advantages over traditional OBC, without any apparent compromise
      in short-term and long-term outcomes. To compare perioperative characteristics,
      short-term, and long-term outcomes for laparoscopic Burch colposuspension (LBC)
      and open Burch colposuspension (OBC) for the treatment of urinary stress
      incontinence. Randomised surgical trial with single blinding. Three tertiary
      level teaching hospitals involving seven surgeons of varying skill levels. Two
      hundred women with urodynamic stress incontinence (USI). The two groups were
      treated in identical fashion, except for the laparoscopic or open approach to
      surgery. Attempts were made to blind the subjects and the observers obtaining
      outcome data to treatment group. Analyses were adjusted for surgeon experience.
      Absence of USI 6 months following surgery, postoperative pain, time spent in
      hospital, and time to return to activities of normal daily living. There were no
      significant differences in objective and subjective measures of cure and in
      patient satisfaction at 6 months, 24 months, or 3-5 years of follow up between
      laparoscopic and open colposuspension groups. Laparoscopic colposuspension took
      longer time to perform (87 versus 42 minutes, P < 0.0001) but was associated with
      less blood loss (P= 0.03), less pain (P= 0.02), and quicker return to normal
      activities (P= 0.01). LBC has significant advantages over traditional OBC,
      without any apparent compromise in short-term and long-term outcomes.

PMID- 16956332
TI  - Laparoscopic versus open colposuspension--results of a prospective randomised
      controlled trial.
AB  - OBJECTIVE: To compare the effectiveness and cost effectiveness of open and
      laparoscopic colposuspension in the treatment of stress urinary incontinence.
      DESIGN: A randomised controlled trial. Women were randomised between March 1999
      and February 2002 and were seen for assessment at 6, 12 and 24 months,
      postoperatively. SETTING: Women were recruited from six gynaecology units in the
      UK. POPULATION: Women with proven stress urinary incontinence requiring surgery.
      METHODS: Open abdominal retropubic colposuspension or laparoscopic
      colposuspension. MAIN OUTCOME MEASURES: Primary outcomes were subjective
      (satisfaction with outcome) and objective (negative 1-hour pad test). Secondary
      outcomes were operative and postoperative morbidity and quality of life. The
      study was powered to demonstrate noninferiority, i.e. that the absolute cure rate
      of laparoscopic colposuspension was no more than 15% below that of open
      colposuspension. RESULTS: A total of 291 women were randomised, with 24-month
      data on subjective and objective outcomes in 88 and 82.5%, respectively. The
      intention-to-treat analysis indicated no significant difference in cure rates
      between open and laparoscopic surgery. The objective cure rates for open and
      laparoscopic were 70.1 and 79.7%, respectively. Subjective cure rates by
      satisfaction were lower than objective cure; 54.6 and 54.9%, respectively, and
      there was considerable nonconcordance both ways. CONCLUSIONS: Laparoscopic
      colposuspension is not inferior to open colposuspension in terms of curing stress
      urinary incontinence.

PMID- 16956333
TI  - Cost-effectiveness analysis of open colposuspension versus laparoscopic
      colposuspension in the treatment of urodynamic stress incontinence.
AB  - OBJECTIVES: To compare the cost effectiveness of laparoscopic versus open
      colposuspension for the treatment of female urinary stress incontinence. DESIGN:
      Cost utility analysis alongside a randomised controlled trial. SETTING: Six
      gynaecological surgical centres within the UK. POPULATION/SAMPLE: Women with
      proven stress urinary incontinence requiring surgery. METHODS: Open abdominal
      retropubic colposuspension or laparoscopic colposuspension carried out by
      experienced surgeons. MAIN OUTCOME MEASURES: Cost, measured in pounds sterling
      and generic health-related quality of life, measured using the EQ-5D. The latter
      was used to estimate patient-specific quality-adjusted life years (QALYs).
      RESULTS: Healthcare resource use over 6-month follow up translated into costs of
      pound 1805 for the laparoscopic arm and pound 1433 for the open arm (differential
      mean cost pound 372; 95% credibility interval [CrI]: 274-471). At 6 months, QALYs
      were slightly higher in the laparoscopic arm relative to the open arm (0.005; 95%
      CrI: -0.012 to 0.023). Therefore, the cost of each extra QALY in the laparoscopic
      group (the incremental cost-effectiveness ratio [ICER]) was pound 74,400 at 6
      months. At 24 months, the laparoscopic arm again had a higher mean QALY score
      compared to the open surgery group. Thus, assuming that beyond 6 months the
      laparoscopic colposuspension would not lead to any significant additional costs
      compared with open colposuspension, the ICER was reduced to pound 9300 at 24
      months. Extensive sensitivity analyses were carried out to test assumptions made
      in the base case scenario. CONCLUSIONS: Laparoscopic colposuspension is not cost
      effective when compared with open colposuspension during the first 6 months
      following surgery, but it may be cost effective over 24 months.

PMID- 16956334
TI  - Psychological wellbeing after laparoscopic and abdominal hysterectomy--a
      randomised controlled multicentre study.
AB  - OBJECTIVE: To compare laparoscopic hysterectomy and abdominal total hysterectomy
      regarding influence on postoperative psychological wellbeing and surgical
      measures. DESIGN: A prospective, open, randomised multicentre trial. SETTING:
      Five hospitals in the South East of Sweden. POPULATION: Hundred and twenty-five
      women scheduled for hysterectomy for benign conditions were enrolled in the
      study, and 119 women completed the study. Fifty-six women were randomised to
      abdominal hysterectomy and 63 to laparoscopic hysterectomy. METHODS: Psychometric
      tests measuring general wellbeing, depression and anxiety preoperatively and 5
      weeks and 6 months postoperatively. MAIN OUTCOME MEASURES: Effects of operating
      method on the psychological wellbeing postoperatively. Analysis of data regarding
      operating time, peroperative and postoperative complications, blood loss,
      hospital stay and recovery time. RESULTS: No significant differences in the
      scores were observed between the two groups in any of the four psychometric
      tests. Both the surgical methods were associated with a significantly higher
      degree of psychological wellbeing 5 weeks postoperatively compared with
      preoperatively. The operating time was significantly longer for the laparoscopic
      hysterectomy group, but the duration of the stay in hospital and sick-leave were
      significantly shorter for laparoscopic hysterectomy group compared with the
      abdominal hysterectomy group. CONCLUSIONS: General psychological wellbeing is
      equal after laparoscopic and abdominal hysterectomy within 6 months after the
      operation. The advantages of the laparoscopic hysterectomy are the shorter stay
      in hospital and shorter sick-leave, but these issues must be balanced by a longer
      duration of the operation.

PMID- 16956335
TI  - Contraceptive effect of sperm-agglutinating factor isolated from Staphylococcus
      aureus in mouse.
AB  - OBJECTIVE: To investigate the contraceptive effect of sperm-agglutinating factor
      (SAF) isolated from Staphylococcus aureus in mouse. DESIGN: Experimental study
      performed with LACA mice obtained from the Central Animal House, Panjab
      University, Chandigarh, India. SETTING: In vivo studies conducted in the
      Department of Microbiology, Panjab University, Chandigarh, India. POPULATION:
      Sixty female and 18 male mice were used for the studies. METHODS: Mice sperm-S.
      aureus agglutination, scanning electron microscopy (SEM), in vivo studies in
      mice. MAIN OUTCOME MEASURE: Contraceptive efficacy of SAF. RESULTS: S. aureus
      readily adhered to and agglutinated mouse spermatozoa. By SEM, S. aureus
      adherence was observed on sperm head as well as sperm tail. SAF was found to be
      causing 100% fertility inhibition in mouse with no effect on vaginal epithelium.
      CONCLUSIONS: Sperm-agglutinating factor has been found to have a potential as a
      contraceptive agent.

PMID- 16956336
TI  - Oxidative stress in midpregnancy as a predictor of gestational hypertension and
      pre-eclampsia.
AB  - OBJECTIVES: To explore the relationship between the levels of maternal oxidative
      stress and glycaemia during pregnancy and to compare the predictive values of 8
      epimer of prostaglandin F(2alpha) (8-isoPGF(2alpha)) and mean arterial pressure
      (MAP) in midpregnancy for the development of hypertensive complications in later
      pregnancy. DESIGN: Prospective observational study as an ancillary study to the
      Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study. SETTING: Obstetric
      clinics and wards of a university teaching hospital in Hong Kong. POPULATION:
      Selected women with singleton pregnancies attending the antenatal clinic.
      METHODS: Pregnant women who met HAPO inclusion criteria were recruited for the
      study. Glucose tolerance was assessed by a 75-g 2-hour oral glucose tolerance
      test (OGTT) at 24-32 weeks of gestation. Fasting plasma samples for 8
      isoPGF(2alpha) estimation and urine samples for 8-isoPGF(2alpha) and 2,3-dinor 8
      isoPGF(2alpha) assays were collected and blood pressures measured during the OGTT
      visit. Random plasma and urine samples were also obtained at 34-37 weeks. Glucose
      results were unblinded to the attending obstetrician if limits preset under the
      HAPO protocol were met. MAIN OUTCOME MEASURES: Maternal plasma 8-isoPGF(2alpha)
      and urinary 8-isoPGF(2alpha) and 2,3-dinor 8-isoPGF(2alpha) both at the time of
      OGTT (24-32 weeks) and at 34-37 weeks of gestation. Incidence of pre-eclampsia
      and gestational hypertension. RESULTS: Of the 408 women who attended for OGTT at
      24-32 weeks, two met the glucose criteria for unblinding and 25 had missing 8
      isoPGF(2alpha) values and thus were excluded from analysis. Of the 381 women, 338
      (88.7%) attended for random plasma samples at 34-37 weeks. Significant
      correlations were observed between maternal fasting plasma isoprostane and both
      fasting (r= 0.20; P < 0.001) and 2-hour (r= 0.39; P < 0.001) plasma glucose
      levels at the time of OGTT. Gestational hypertension/pre-eclampsia occurred in 17
      (4.2%) women, and at the time of OGTT, they had significantly higher fasting
      plasma 8-isoPGF(2alpha) (P < 0.001), urine 8-isoPGF(2alpha) (P < 0.005) and urine
      2,3-dinor 8-isoPGF(2alpha) to creatinine ratios (P < 0.001), as well as higher
      MAP (P < 0.001) than women who remained normotensive. At 34-37 weeks, only random
      plasma 8-isoPGF(2alpha) was significantly higher (P < 0.001) among the women with
      gestational hypertension/pre-eclampsia. CONCLUSIONS: Plasma markers of oxidative
      stress were positively correlated with plasma glucose at the time of OGTT (24-32
      weeks). Women who subsequently developed gestational hypertension/pre-eclampsia
      had significantly higher plasma and urine markers of oxidative stress at the time
      of OGTT but only higher plasma markers at 34-37 weeks. Plasma 8-isoPGF(2alpha)
      appears to be a very good predictor of subsequent gestational hypertension/pre
      eclampsia when measured at the time of OGTT, but its ability to discriminate
      deteriorates as pregnancy advances.

PMID- 16956337
TI  - Factors associated with the awareness and practice of evidence-based obstetric
      care in an African setting.
AB  - OBJECTIVE: To identify the factors associated with important (> or =50%)
      variation in awareness and practice of evidence-based obstetric interventions in
      an African setting where we have previously reported poor awareness and use of
      evidence-based reproductive interventions. DESIGN: Cross-sectional analysis of
      data from our Reproductive Health Interventions Study. SETTING: North-west
      province, Cameroon, Africa. POPULATION: Health workers including obstetricians,
      other physicians, midwives, nurses and other staff providing reproductive care.
      MAIN OUTCOME MEASURES: Prevalence ratios (PR) of uniform awareness and practice
      of four key evidence-based obstetric interventions from the World Health
      Organization Reproductive Health Library (WHO RHL): antiretrovirals to prevent
      mother-to-child transmission of HIV/AIDS, antenatal corticosteroids for
      prematurity, uterotonics to prevent postpartum haemorrhage and magnesium sulphate
      for seizure prophylaxis. METHODS: Comparisons of descriptive covariates, applying
      logistic regression to estimate independent relationships with awareness and use
      of evidence-based interventions. RESULTS: A total of 15.5% (50/322) of health
      workers were aware of all the four interventions while only 3.8% (12/312)
      reported optimal practice. Evidence-based awareness was strongly associated with
      practice (PR = 15.4; 96% CI: 4.3-55.0). Factors significantly associated with
      awareness were: attending continuing education, access to the WHO RHL, employment
      as an obstetrician/gynaecologist and working in autonomous military or National
      Insurance Fund facilities. Controlling for potential confounding, working as an
      obstetrician was associated with increased awareness (adjusted prevalence odds
      ratio [aPOR] = 8.3; 95% CI: 1.3-53.8) as was median work experience of 5-15 years
      (aPOR = 2.0; 95% CI: 1.0-3.8). Internet access was associated with increased
      practice (aPOR = 3.4; 95% CI: 1.0-11.8). Other potentially important variations
      were observed, although they did not attain statistical significance.
      CONCLUSIONS: Several factors including obstetric training and continuous
      education positively influence evidence-based awareness and practice of key
      obstetric interventions. Confirmation and application of this information may
      enhance the effectiveness of programmes to improve maternal and perinatal
      outcomes.

PMID- 16956338
TI  - Fasting capillary glucose as a screening test for gestational diabetes mellitus.
AB  - OBJECTIVE: To evaluate fasting capillary glucose as a screening test for
      gestational diabetes mellitus (GDM) compared with traditional risk factors and
      repeated random capillary glucose measurements. DESIGN: Cross-sectional,
      population-based study. SETTING: Maternal Health Care Clinics in Orebro County,
      Sweden. POPULATION: An unselected population of women without diabetes. METHODS:
      Fasting capillary glucose levels were measured at gestational weeks 28-32. Random
      capillary glucose levels were measured four to six times during pregnancy.
      Traditional risk factors for GDM were registered. GDM was diagnosed using a 75-g
      oral glucose tolerance test. MAIN OUTCOME MEASURES: Sensitivity, specificity,
      likelihood ratios. RESULTS: In 55 of 3616 women participating in the study, GDM
      was diagnosed before 34 weeks of gestation. For fasting capillary glucose cutoff
      values between 4.0 and 5.0 mmol/l, sensitivity was in the range between 87 and
      47% and specificity between 51 and 96%. Using a combined screening model of
      traditional risk factors with fasting capillary glucose at various cutoff values
      increased the sensitivity only slightly compared with using fasting capillary
      glucose alone. CONCLUSION: In this Swedish, unselected, low-risk population,
      fasting capillary glucose measurements were found to be an acceptable and useful
      screening test for GDM.

PMID- 16956339
TI  - Prenatal isolated mild ventriculomegaly: outcome in 167 cases.
AB  - OBJECTIVE: To define the contribution of prenatal investigation and evaluate the
      prognosis of isolated mild ventriculomegaly (IMV). DESIGN: Retrospective study.
      SETTING: University hospital between January 1992 and December 2002. POPULATION:
      One hundred and sixty-seven cases of prenatal unilateral or bilateral IMV without
      any associated anomaly at the time of initial diagnosis. METHODS: Complementary
      investigations were performed: amniocentesis with karyotyping, screening for
      viruses and acetylcholinesterase electrophoresis, magnetic resonance imaging
      (MRI), and ultrasonography every 3-4 weeks. MAIN OUTCOME MEASURES: Results of
      prenatal investigations, pregnancy outcome, and postnatal psychomotor
      development. RESULTS: IMV was diagnosed around 26.5 weeks. Amniocentesis revealed
      four chromosomal anomalies and two cytomegalovirus infections. MRI diagnosed
      brain-associated anomalies in 15 cases and ultrasonographic monitoring
      highlighted malformations not initially diagnosed in 28 cases. Termination of
      pregnancy (TOP) was considered in 21 pregnancies (12.6%). Indications were
      aneuploidy, fetal infectious disease or associated malformations. In women for
      whom a TOP was considered, consanguinity, fetus of female sex and frontal horn
      enlargement were statistically more frequent, ventriculomegaly was more often
      bilateral and asymmetrical, atrial width, and the rate of progressive ventricular
      enlargement were significantly higher. One hundred and one children with prenatal
      IMV were assessed between 19 and 127 months (mean age 54.68 +/- 2.87 months).
      Twelve children had neurological disease or psychomotor delay and 89 children had
      a normal psychomotor development. Poor neurological outcome was more often
      associated with atrial width greater than or equal to 12 mm, asymmetrical
      bilateral enlargement, and progression of the ventriculomegaly. CONCLUSION: The
      detection of IMV raises the question of the child's psychomotor development and
      justifies meticulous prenatal investigation. In addition to associated anomalies,
      three criteria are often associated with an unfavourable outcome: atrial width
      greater than 12 mm, progression of the enlargement, and asymmetrical and
      bilateral ventriculomegaly.

PMID- 16956340
TI  - A cost-effectiveness analysis of the intrapartum fetal pulse oximetry multicentre
      randomised controlled trial (the FOREMOST trial).
AB  - OBJECTIVE: To report an economic analysis of the Australian intrapartum fetal
      pulse oximetry (FPO) multicentre randomised controlled trial (the FOREMOST
      trial), which examined whether adding FPO to conventional cardiotocographic (CTG)
      monitoring (intervention group) was cost-effective in reducing operative delivery
      rates for non-reassuring fetal status compared with the use of CTG alone (control
      group). DESIGN: Cost-effectiveness analysis of the FOREMOST trial. SETTING: Four
      Australian maternity hospitals, each with more than 4000 births/year. POPULATION:
      Women in labour at > or =36 weeks of gestation, with a non-reassuring CTG.
      METHODS: Costs were for treatment-related expenses, incorporating diagnosis
      related grouping costs and direct costs (including fetal monitoring). Incremental
      cost-effectiveness ratio (ICER) and cost-effectiveness plane were calculated, and
      sensitivity analysis was conducted. The primary outcome was that of the clinical
      trial: operative delivery for non-reassuring fetal status avoided in the
      intervention group relative to that in the control group. MAIN OUTCOME MEASURES:
      The ICER. RESULTS: The ICER demonstrated a saving of $A813 for each operative
      birth for non-reassuring fetal status averted by the addition of FPO to CTG
      monitoring compared with the use of CTG monitoring alone. CONCLUSION: The
      addition of FPO to CTG monitoring represented a less costly and more effective
      use of resources to reduce operative delivery rates for non-reassuring fetal
      status than the use of conventional CTG monitoring alone.

PMID- 16956341
TI  - Oral inosiplex in the treatment of cervical condylomata acuminata: a randomised
      placebo-controlled trial.
AB  - Conventional therapies for human papillomavirus infection aim to remove
      clinically apparent lesions, while latent infection may remain, representing a
      threat for transmission and carcinogenesis. The use of a systemic agent may more
      effectively control the virus. We conducted a randomised placebo-controlled study
      to investigate the efficacy and safety of oral inociplex in the treatment of
      cervical condylomata acuminata (CA) that had been resistant to conventional
      therapies. Thirty-eight white European women, aged 20-43 years, with genital
      warts of the cervix, refractory to at least one conventional therapy, were
      randomly assigned to receive either inosiplex, 50 mg/kg daily peros for 12 weeks
      (group 1), or placebo (group 2). Of the 17 evaluable group 1 women, 4 responded
      to the treatment completely, 7 responded partially and 6 did not respond. Of the
      19 group 2 women, none responded to the treatment completely, 3 responded
      partially and 16 did not respond. The therapeutic difference between women
      receiving active and placebo therapy was statistically significant (chi(2)= 6.69,
      P < 0.01) and remained significant when an intention-to-treat analysis was
      performed (chi(2)= 7.69, P < 0.01). None of the complete responders experienced
      recurrence during the 12-month follow up. Adverse effects were mild and resolved
      upon completion of therapy. Compared with placebo, inosiplex showed considerable
      efficacy with insignificant and reversible adverse effects and without
      recurrences. Inosiplex may represent an efficacious and safe alternative systemic
      form of therapy for cervical genital warts.

PMID- 16956342
TI  - Adjusting bladder neck sling length to maximise same-day voiding.
AB  - The bladder neck fascial sling may become a more popular procedure if surgical
      modifications could ensure more rapid postoperative voiding, yet not compromising
      the 85% long-term cure rate. In a study of 80 women, we found that increasing the
      distance from the Prolene knot to the rectus fascia, while simultaneously
      observing the closure of the bladder neck with a cystoscope, resulted in 92% of
      women voiding the same day and 93% experiencing no stress incontinence at 1 year.

PMID- 16956343
TI  - Acute postpartum uterine inversion with haemorrhagic shock: laparoscopic
      reduction: a new method of management?

PMID- 16956344
TI  - A comparison of intrapartum automated fetal electrocardiography and conventional
      cardiotocography--a randomised controlled study.

PMID- 16956345
TI  - Go6976 is a potent inhibitor of the JAK 2 and FLT3 tyrosine kinases with
      significant activity in primary acute myeloid leukaemia cells.
AB  - Aberrant activation of Janus kinase/signal transducers and activators of
      transcription (JAK/STAT) signalling is implicated in a number of haematological
      malignancies and effective JAK inhibitors may be therapeutically useful. We found
      that Go6976, an indolocarbazole inhibitor of the calcium-dependent isozymes of
      protein kinase C (PKC), inhibited interleukin 3/granulocyte-macrophage colony
      stimulating factor-induced signalling, proliferation and survival whereas Go6983,
      a broad spectrum PKC inhibitor, had no such effects. Go6976 was found to be a
      direct and potent inhibitor of JAK2 in vitro. Go6976 also inhibited signalling,
      survival and proliferation in cells expressing the leukaemia-associated TEL-JAK2
      fusion protein and the myeloproliferative disorder (MPD)-associated JAK2 V617F
      mutant. In primary acute myeloid leukaemia (AML) cells, incubation with Go6976
      reduced constitutive STAT activity in all cases studied. In addition, Akt and
      mitogen-activated protein kinase phosphorylation were reduced in 4/5 FLT3
      internal tandem duplication (ITD) positive AML cases and 7/13 FLT3-wild-type (WT)
      cases. Expression of FLT3-WT, ITD and D835Y in 32D cells showed that Go6976 is
      also a potent inhibitor of WT and mutant FLT3. In AML cells, Go6976 reduced the
      survival to 55 +/- 5% of control in FLT3-ITD cases and to 69 +/- 5% in FLT3-WT
      samples. These data may help identify clinically useful compounds based on the
      structure of Go6976, which can be employed for the treatment of MPDs as well as
      AML.

PMID- 16956346
TI  - The management of heparin-induced thrombocytopenia.

PMID- 16956347
TI  - Modern diagnosis and management of the porphyrias.
AB  - Recent advances in the molecular understanding of the porphyrias now offer
      specific diagnosis and precise definition of the types of genetic mutations
      involved in the disease. Molecular diagnostic testing is powerful and very useful
      in kindred evaluation and genetic counselling when a disease-responsible mutation
      has been identified in the family. It is also the only way to properly screen
      asymptomatic gene carriers, facilitating correct treatment and appropriate
      genetic counselling of family members at risk. However, it should be noted that
      DNA-based testing is for the diagnosis of the gene carrier status, but not for
      the diagnosis of clinical syndrome or severity of the disease, e.g. an acute
      attack. For the diagnosis of clinically expressed porphyrias, a logical stepwise
      approach including the analysis of porphyrins and their precursors should not be
      underestimated, as it is still very useful, and is often the best from the cost
      effective point of view.

PMID- 16956348
TI  - JAK2 V617F mutation in leukaemic transformation of philadelphia-negative chronic
      myeloproliferative disorders.

PMID- 16956349
TI  - Occurrence of the same chromosome abnormalities in Ph+ and Ph- cells in chronic
      myeloid leukaemia. Evidence of a secondary origin of the Ph chromosome?

PMID- 16956350
TI  - Medium-term experience of sacral neuromodulation by tined lead implantation.
AB  - OBJECTIVE: To describe patient selection for sacral neuromodulation, also known
      as Interstim therapy, and the results of tined-lead implantation in the medium
      term. PATIENTS AND METHODS: In all, 49 patients, 39 with refractory overactive
      bladder symptoms and 10 with urinary retention, were implanted with the tined
      lead under local anaesthesia. The mean (sd) test period was 12.4 (5.8) days.
      Patients were implanted when they had a > or = 50% improvement in voiding diary
      variables during the test period. The mean follow-up for implanted patients was
      15.5 (7.9) months. Changes in voiding variables were compared using a t-test.
      RESULTS: Ten patients had a one-stage and 39 a two-stage implant; of the latter
      group, 31 (80%) had a positive response and eight (21%) did not. In all, 31
      patients were included in the follow-up. At the last follow-up, 28 (90%) patients
      had a >50% improvement in diary variables and three (10%) did not. In 21 patients
      with urgency symptoms the mean (sd) number of voids decreased from 11.7 (8.9)/day
      at baseline to 7.3 (3.4)/day (P = 0.1); the voided volume increased from 160.2
      (70.7) mL to 231.1 (119.5) mL (P = 0.001); and the number of leakages decreased
      from 9.5 (8.7) to 3.3 (2.2)/day (P = 0.17). In the 10 patients with retention,
      the number of catheterizations decreased from 5.44 (1.6)/day with a volume of
      297.6 (76.8) mL, to 1.2 (1.7)/day and 111.6 (158.1) mL; the mean number of voids
      increased from 3.7 (3.8)/day with a volume of 123.3 (141.7) mL, to 4.2 (2.4)/day
      and 248.3 (146.0)mL. There were no significant differences in the variables in
      the patients with retention. Seven patients had an adverse event. There was one
      incomplete electrode migration that was treated conservatively. CONCLUSION: This
      new minimally invasive approach gives positive results in the medium term. Two
      stage testing with the tined lead seems more reliable than the classic
      percutaneous nerve evaluation. The lead anchoring method seems sufficient for
      fixing the electrode in the medium term.

PMID- 16956351
TI  - Erythropoietin administration protects against functional impairment and cell
      death after ischaemic renal injury in pigs.
AB  - OBJECTIVE: To determine whether the administration of erythropoietin at the time
      of ischaemic renal injury (IRI) inhibits apoptosis, enhances tubular epithelial
      regeneration and promotes renal functional recovery, as it does in rodent models,
      in a higher mammalian model. MATERIALS AND METHODS: The model of IRI involved
      unilateral nephrectomy in pigs, followed a week later by renal artery occlusion
      for 1 h, followed by reperfusion for 5 days. Pigs were randomized to receive
      erythropoietin 5000 units/kg intravenously at the time of ischaemia, followed by
      1000 units/kg subcutaneously daily, or no treatment (six pigs each). Renal
      function and structure were analysed; blood and urine were collected daily to
      determine serum creatinine level, blood urea nitrogen, and creatinine clearance.
      Animals were killed after 5 days to obtain the injured kidneys. The kidneys were
      examined histologically for evidence of cellular mitosis, apoptosis and necrosis.
      RESULTS: Erythropoietin significantly abrogated renal dysfunction after IRI
      compared with controls at 12 h after injury; the mean (sem) creatinine clearance
      (as a percentage of baseline) for IRI was 68.2 (6)% vs erythropoietin-IRI 94.9
      (8.9)% (P = 0.027), although by 36 h this was no longer significant, with values
      of 73.8 (12.7)% vs 95.9 (12)%, respectively (P = 0.23). Erythropoietin also
      significantly reduced the amount of cell death on histological analysis after 5
      days of reperfusion, with a median (range) for IRI of 5.5 (1-45) vs
      erythropoietin-IRI of 1.5 (0-4) (P = 0.043). CONCLUSION: This study confirms the
      potential clinical applications of erythropoietin as a novel therapeutic agent in
      patients at risk of IRI.

PMID- 16956352
TI  - Unilateral renal agenesis and the congenital solitary functioning kidney:
      developmental, genetic and clinical perspectives.

PMID- 16956353
TI  - Outcomes in patients with urothelial carcinoma of the bladder with limited pelvic
      lymph node dissection.
AB  - OBJECTIVES: To evaluate the rates of local and systemic progression (LP and SP),
      recurrence-free survival and overall survival for patients with urothelial
      carcinoma of the bladder with limited pelvic lymph node dissection (PLND) in 1987
      2000. PATIENTS AND METHODS: A consecutive series was analysed of 385 patients
      (median age 61.9 years, range 30.7-83.8) treated by limited bilateral PLND and
      radical cystectomy (RC) between 1987 and 2000, with negative surgical margins on
      final pathology. All patients were staged N0M0 before RC, and none received
      neoadjuvant radiotherapy or chemotherapy. The boundaries of the limited PLND were
      the pelvic side-wall between the genitofemoral and obturator nerves, and
      bifurcation of iliac vessels to the circumflex iliac vein. LP was defined as a
      radiographic soft-tissue density of > or = 2 cm below the bifurcation of the
      aorta. Pathological characteristics, based on the 1997 Tumour-Nodes-Metastasis
      system, recurrence patterns, and recurrence-free and overall survival, were
      determined. RESULTS The median (range) overall follow-up was 45.1 (1.1-165.6)
      months; the number of lymph nodes (LNs) reported per patient was 12 (2-32). Of
      the 385 patients, 130 (33.8%) had evidence of LP and 60 (15.6%) of SP. The 5-year
      recurrence-free and overall survival rates were both 71% for patients with organ
      confined, N0 tumours, and 23% and 26% for unconfined, N0 tumours. Positive LNs
      were found in 45 (12%) patients, who had a recurrence-free and overall survival
      rate of 9% at 5 years. CONCLUSION: Compared with published reports of similar
      cohorts of patients managed with RC and extended PLND, the present study suggests
      that limited PLND is associated with suboptimal staging, greater rates of LP, and
      lower rates of recurrence-free survival, particularly for patients with
      unconfined or LN-positive disease.

PMID- 16956354
TI  - Pre-clinical evidence for the use of phosphodiesterase-5 inhibitors for treating
      benign prostatic hyperplasia and lower urinary tract symptoms.
AB  - OBJECTIVE: To evaluate the potential of sildenafil, vardenafil and tadalafil, all
      phosphodiesterase-5 (PDE-5) inhibitors used for treating erectile dysfunction,
      for treating benign prostatic hyperplasia (BPH) and lower urinary tract symptoms
      (LUTS). MATERIALS AND METHODS: The mRNA expression of the PDE-5 was determined in
      rat LUT tissues. The PDE-5 inhibitors were also tested in organ-bath experiments
      and in a partial bladder outlet obstruction (BOO) rat model in vivo. RESULTS: The
      highest PDE-5 mRNA expression was in the bladder, followed by the urethra and
      prostate. PDE-5 inhibitors dose-dependently reduced the contraction of the
      isolated bladder, urethral and prostate strips. The rank order of potency was
      vardenafil > sildenafil > tadalafil. In human prostate stromal cells vardenafil
      inhibited cell proliferation and was more effective than tadalafil and
      sildenafil. In the BOO model, there was a reduction in the non-voiding
      contractions after bolus intravenous administration of 3 mg/kg sildenafil and
      vardenafil. CONCLUSION: These results show that PDE-5 is expressed in LUT
      tissues. PDE-5 inhibitors induced significant relaxation of these tissues,
      inhibited the proliferation of human prostate stromal cells and reduced the
      irritative symptoms of BPH/LUTS in vivo. Therefore, PDE-5 inhibitors could be
      used as an effective treatment for BPH/LUTS.

PMID- 16956355
TI  - A systematic review of the reliability of frequency-volume charts in urological
      research and its implications for the optimum chart duration.
AB  - OBJECTIVE: To determine how the reliability of frequency-volume charts (FVCs)
      vary with their duration when used to assess patients with lower urinary tract
      symptoms (LUTS) and whether the duration influences patient compliance. METHODS:
      Peer-reviewed studies involving patients with LUTS were searched systematically,
      with the selected studies assessed for their internal and external validity and
      statistical quality. Details of the patients and type of FVC used were
      summarized, and reliability coefficients and levels of compliance were extracted
      for commonly assessed FVC variables. RESULTS: In all, 13 studies were considered
      to meet the review criteria; they assessed the reliability of FVCs lasting 1, 2,
      3 and 7 days. The reliability coefficients for 3- and 7-day FVCs were generally
      >0.8; those for shorter charts tended to be lower, but strong conclusions could
      not be drawn due to study limitations. There was no obvious relationship between
      the duration of the FVC and the level of compliance. CONCLUSIONS: Strong
      recommendations cannot be made about what duration of an FVC should be used to
      assess or monitor patients with LUTS. The current consensus on using FVCs of > or
      = 3 days seems to be the most defensible policy, but more research of high
      quality is required, especially into the relationship of FVC duration with
      compliance.

PMID- 16956356
TI  - Pudendal nerve stimulation of a preparation of isolated guinea-pig urethra.
AB  - OBJECTIVE: To assess the functional response of the urethral striated muscle to
      activation of its nerves, using a novel isolated organ-bath preparation.
      MATERIALS AND METHODS: The urethra of the female guinea-pig was chosen as a
      suitable model for investigation, as it is functionally and structurally similar
      to the human urethra. Female Dunkin-Hartley guinea-pigs (400-500 g) were used;
      for the histochemical and immunohistochemical experiments, unfixed urethras were
      cryo-sectioned (14 microm thick) and were stained using established methods. For
      in vitro experiments, whole urethras were suspended vertically, with pudendal
      nerves intact, for isometric tension and intraluminal pressure recording in a 40
      mL organ bath. Drugs were applied directly to the bathing solution. RESULTS: In
      the striated muscle layer of the urethra there was positive beta-NADPH-diaphorase
      activity. In organ-bath studies the pudendal nerve-evoked contractions (0.2 ms
      pulses, 5 s trains, 70 V and 1-100 Hz) were abolished in the presence of
      tubocurarine (10(-6)m), and unaffected by guanethidine and atropine (both 10(
      6)m). Pre-incubation with sodium nitroprusside and SIN-1 chloride significantly
      reduced the initial peak pressure responses (P < 0.05, anova for paired data)
      evoked by electrical field stimulation of the pudendal nerves at stimulus
      parameters of 0.2 ms pulses, 5 s trains, 70 V and 25 Hz. CONCLUSION: Electrically
      induced contractions were abolished by tubocurarine, confirming that the pudendal
      nerve innervates the striated muscle of the guinea-pig external urethral
      sphincter via nicotinic receptors. beta-NADPH-diaphorase histochemistry gave
      positive staining around guinea-pig striated muscle cells and possibly identified
      neuromuscular junction sites staining positively for the nitric oxide synthase
      marker. Together with the results of the organ-bath experiments, the results
      suggest that the striated muscle cells of the guinea-pig urethra have the
      machinery to respond to nitric oxide.

PMID- 16956357
TI  - Increased preoperative serum C-reactive protein level predicts a poor prognosis
      in patients with localized renal cell carcinoma.
AB  - OBJECTIVE: To evaluate the value of the preoperative serum C-reactive protein
      (CRP) level in the prognosis of patients with localized renal cell carcinoma
      (RCC). PATIENTS AND METHODS: The study comprised 101 patients who had a radical
      nephrectomy for localized RCC (pT1-3N0M0). An elevated CRP was defined as >0.5
      mg/dL before surgery. Survival rates for each variant were calculated using the
      Kaplan-Meier method, with the difference between survival curves evaluated using
      the log-rank test. Multivariate analysis was by Cox proportional hazard model;
      for all analyses the difference was considered significant when P < 0.05.
      RESULTS: The median (range) follow-up was 55 (2-187) months; 26 patients (26%)
      had high CRP levels, and 12 (46%) of these and three (4.0%) of the remaining 75
      died from disease. The 5- and 10-year disease-specific survival rates (75% and
      30%, respectively) in patients with high CRP levels were significantly worse than
      those in patients with normal CRP levels (both 93%, P < 0.001). In other
      variants, preoperative haemoglobin concentration, pathological stage, grade,
      histological type and microvascular tumour invasion were also related to disease
      specific survival. By the Cox proportional hazards model, pathological stage and
      an elevated CRP were the most important prognostic factors for disease-specific
      survival in patients with localized RCC (P = 0.008 and 0.012, respectively).
      CONCLUSION: The preoperative CRP level was associated with poor survival in
      patients with localized RCC.

PMID- 16956358
TI  - The use of a suprascrotal or 'wink' incision for placing a testicular prosthesis.
AB  - OBJECTIVE: To describe a suprascrotal technique of testicular prosthesis
      insertion that obviates the difficulties and complications associated with either
      the inguinal or scrotal approach, as although the insertion of a testicular
      prosthesis is common there are few reports of the various techniques of
      insertion, associated complication rates, and patient satisfaction. PATIENTS AND
      METHODS: Eight males (aged 14-26 years) who had had a previous orchidectomy, had
      a testicular prosthesis inserted using a suprascrotal incision. A 2-cm semilunar
      incision is made just above the scrotum, 2-3 cm lateral to the penis ('wink'
      incision). The prosthesis is inserted after developing the intrascrotal space
      with blunt dissection. All patients tolerated the procedure well and all were
      outpatient procedures. RESULTS: After a median follow-up of 12 months, all
      patients were satisfied with the aesthetics of the prosthesis. Incisions were
      hidden by pubic hair. There were no wound infections at the incision site, and no
      reports of any pain or discomfort associated with the prosthesis. CONCLUSION: The
      'wink' incision is an attractive alternative for inserting a testicular
      prosthesis; the advantages of the suprascrotal approach include: (i) the incision
      is hidden by pubic hair; (ii) no difficult dissection through fibrotic tissue in
      patients who have had previous inguinal surgery; and (iii) avoidance of direct
      contact between the prosthesis and suture line, minimizing the risk of infection,
      erosion and postoperative pain, while maintaining a pouch of adequate size.

PMID- 16956359
TI  - Management of incidental impalpable intratesticular masses of < or = 5 mm in
      diameter.
AB  - OBJECTIVE: To gain more insight into the histology of small incidental
      intratesticular lesions and evaluate the need for surgical management, as
      exploratory surgery is the only way to exclude malignancy in testicular tumours.
      PATIENTS AND METHODS: Between September 2000 and April 2005, incidental
      intratesticular masses of < or = 5 mm in diameter were found in 20 men undergoing
      scrotal ultrasonography for reasons other than suspected testicular tumour. After
      staging, an organ-sparing approach including frozen-section analysis was used to
      obtain histological data. RESULTS: The mean diameter of the detected tumour
      masses was 3.5 mm, and the mean (range) age of the patients was 36.4 (26-58)
      years. Four men (20%) had orchidectomy because the tumours were found to be
      malignant; the resected specimens yielded multifocal testicular intraepithelial
      neoplasia (TIN) in all patients and additional seminomatous tumour cells
      elsewhere in the testis in one. Frozen-section results were false-negative in one
      patient and he had orchidectomy after having established the definitive
      histological diagnosis. The 16 patients with benign lesions were correctly
      diagnosed and their testicles were not removed. CONCLUSIONS: Advanced and
      innovative ultrasonography technology allows the detection of increasingly small
      testicular masses. In the present series, most incidental intratesticular lesions
      were benign. In patients with malignant lesions, multifocal TIN and/or distant
      seminomatous foci were present despite the tumour being small. Therefore, it is
      essential to perform exploratory surgery as it is the only way to obtain accurate
      histological findings, thus providing oncological efficacy and precluding removal
      of a testicle bearing a benign lesion.

PMID- 16956360
TI  - Over-expression of hypoxia-inducible factor-1alpha increases the invasive potency
      of LNCaP cells in vitro.
AB  - OBJECTIVE: To evaluate the effect of hypoxia-inducible factor-1alpha (HIF-1alpha)
      over-expression on the invasion-associated proteins in human prostate cancer
      cells, as HIF-1alpha is a transcriptional factor that could activate genes
      involved in the response to hypoxia, but might also enhance the invasive potency
      of prostate cancer cells. MATERIALS AND METHODS: Prostate cancer (LNCaP) cells
      were transfected with recombinant plasmid pcDNA3.1(-)/HIF-1alpha and pcDNA3.1(-)
      control vector using a commercial system, designated as LNCaP/HIF-1alpha and
      LNCaP/pcDNA3.1, respectively. The positive clones were selected with G418 and
      confirmed by Western blot and indirect immunofluorescence labelling. A
      polycarbonate filter, coated with a matrix gel, was used to analyse the invasive
      potency. The expression of E-cadherin, vimentin, cathepsin D, matrix
      metalloproteinase (MMP2) and urokinase plasminogen activator receptor (uPAR) was
      detected by Western blot. RESULTS: The expression level of HIF-1alpha in
      LNCaP/HIF-1alpha was distinctly higher than that in LNCaP/pcDNA3.1 and LNCaP.
      Many more cells of LNCaP/HIF-1alpha penetrated through the polycarbonate filter
      than those of LNCaP/pcDNA3.1 and LNCaP. Compared with the LNCaP/pcDNA3.1 and
      LNCaP cells, the expression of vimentin, cathepsin D, MMP-2 and uPAR were up
      regulated in LNCaP/HIF-1alpha, whereas the expression of E-cadherin was down
      regulated. CONCLUSION: These results show that over-expression of HIF-1alpha
      directly stimulates the invasive potency of human prostate carcinoma LNCaP cells
      through the matrix gel. The expression of E-cadherin, vimentin, cathepsin D, MMP
      2 and uPAR, which are proteins with established roles in the pathophysiology of
      invasion, could be regulated by HIF-1alpha in human prostate cancer cells.

PMID- 16956361
TI  - Sustained beneficial effects of intraprostatic botulinum toxin type A on lower
      urinary tract symptoms and quality of life in men with benign prostatic
      hyperplasia.
AB  - OBJECTIVE: To present a comprehensive experience with intraprostatic botulinum
      toxin-type A (BoNT-A) injection in men with symptomatic benign prostatic
      hyperplasia (BPH) and to assess the efficacy on lower urinary tract symptoms
      (LUTS) and quality of life (QoL). PATIENTS AND METHODS: In all, 41 men (mean age
      69.1 years, sd 7.1 ) with an International Prostate Symptom Score of > or = 8,
      peak flow rate of < 12 mL/s, and who were refractory to medical treatment were
      injected with BoNT-A (Botox, Allergan, Inc., CA, USA) at 100 U (21 men, for
      prostate volume < 30 mL) or 200 U (20, for prostate volume > 30 mL) into the
      prostate transperineally under transrectal ultrasonography guidance. Study
      exclusion criteria were confirmed or suspected malignancy, previous pelvic
      surgery or trauma and previous invasive treatment for BPH. The clinical effects
      were evaluated at baseline and at 1, 3 and 6 months after treatment. RESULTS:
      There were no significant local or systemic side-effects in any men. LUTS and QoL
      indices improved by > 30% in 31 of the 41 men (76%), and four of five men with
      urinary retention for > 1 month could void spontaneously at 1 week to 1 month
      after the BoNT-A injection. In 12 of 41 men (29%) there was no change in prostate
      volume, yet seven of these men still had a > 30% improvement in maximum flow
      rate, LUTS and QoL. The efficacy was sustained at 12 months. CONCLUSION: BoNT-A
      injected into the prostate is safe and effective for men with symptomatic BPH.
      The mechanisms of relief of symptoms might not depend totally on the volume
      shrinkage; the inhibitory effect on the smooth muscle tone and aberrant sensory
      function might also be important.

PMID- 16956362
TI  - The medical management of prostate cancer: a multidisciplinary team approach.

PMID- 16956363
TI  - Protective effect of dietary curcumin and capsaicin on induced oxidation of low
      density lipoprotein, iron-induced hepatotoxicity and carrageenan-induced
      inflammation in experimental rats.
AB  - The beneficial influence of dietary curcumin, capsaicin and their combination on
      the susceptibility of low-density lipoprotein (LDL) to oxidation was examined in
      an animal study. Individually, both dietary curcumin and capsaicin significantly
      inhibited the in vivo iron-induced LDL oxidation, as well as copper-induced
      oxidation of LDL in vitro. The protective effect of the combination of curcumin
      and capsaicin on LDL oxidation was greater than that of individual compounds.
      This protective influence of spice principles was also indicated by the relative
      anodic electrophoretic mobility of oxidized LDL on agarose gel. In another study,
      rats injected with iron showed hepatic toxicity as measured by an increase in
      lipid peroxides and elevated serum enzymes, alanine aminotransferase, aspartate
      aminotransferase and lactate dehydrogenase. Dietary curcumin, capsaicin and their
      combination reduced the activities of these enzymes, and lowered the liver lipid
      peroxide level, indicating amelioration of the severity of iron-induced
      hepatotoxicity. In yet another study, a comparison of the extent of carrageenan
      induced paw inflammation showed that both dietary curcumin and capsaicin
      moderately lowered inflammation, while the spice principles in combination were
      more effective. Dietary curcumin and capsaicin significantly decreased the
      activity of 5'-lipoxygenase activity in the polymorphonuclear lymphocytes in
      carrageenan-injected rats, the decrease being even higher in the case of
      combination of these two spice principles. Results suggest that dietary curcumin
      and capsaicin individually are protective to LDL oxidation both in vivo and in
      vitro, to iron-induced hepatotoxicity and to carrageenan-induced inflammation.
      This beneficial effect was higher when the two compounds were fed in combination.

PMID- 16956364
TI  - Binding of human centrin 2 to the centrosomal protein hSfi1.
AB  - hSfi1, a human centrosomal protein with homologs in other eukaryotic organisms,
      includes 23 repeats, each of 23 amino acids, separated by 10 residue linkers. The
      main molecular partner in the centrosome is a small, calcium-binding EF-hand
      protein, the human centrin 2. Using isothermal titration calorimetry experiments,
      we characterized the centrin-binding capacity of three isolated hSfi1 repeats,
      two exhibiting the general consensus motif and the third being the unique Pro
      containing human repeat. The two standard peptides bind human centrin 2 and its
      isolated C-terminal domain with high affinity (approximately 10(7) M(-1)) by an
      enthalpy-driven mechanism, with a moderate Ca2+ dependence. The Pro-containing
      repeat shows a binding affinity that is two orders of magnitude lower. The target
      binding site is localized within the C-terminal domain of human centrin 2.
      Fluorescence titration and NMR spectroscopy show that the well-conserved Trp
      residue situated in the C-terminus of each repeat is deeply embedded in a protein
      hydrophobic cavity, indicating that the peptide direction is reversed relative to
      previously studied centrin targets. The present results suggest that almost all
      of the repeats of the Sfi1 protein may independently bind centrin molecules. On
      the basis of this hypothesis and previous studies on centrin self-assembly, we
      propose a working model for the role of centrin-Sfi1 interactions in the dynamic
      structure of centrosome-associated contractile fibers.

PMID- 16956365
TI  - Alpha-conotoxin analogs with additional positive charge show increased
      selectivity towards Torpedo californica and some neuronal subtypes of nicotinic
      acetylcholine receptors.
AB  - Alpha-conotoxins from Conus snails are indispensable tools for distinguishing
      various subtypes of nicotinic acetylcholine receptors (nAChRs), and synthesis of
      alpha-conotoxin analogs may yield novel antagonists of higher potency and
      selectivity. We incorporated additional positive charges into alpha-conotoxins
      and analyzed their binding to nAChRs. Introduction of Arg or Lys residues instead
      of Ser12 in alpha-conotoxins GI and SI, or D12K substitution in alpha-conotoxin
      SIA increased the affinity for both the high- and low-affinity sites in membrane
      bound Torpedo californica nAChR. The effect was most pronounced for [D12K]SIA
      with 30- and 200-fold enhancement for the respective sites, resulting in the most
      potent alpha-conotoxin blocker of the Torpedo nAChR among those tested.
      Similarly, D14K substitution in alpha-conotoxin [A10L]PnIA, a blocker of neuronal
      alpha7 nAChR, was previously shown to increase the affinity for this receptor and
      endowed [A10L,D14K]PnIA with the capacity to distinguish between acetylcholine
      binding proteins from the mollusks Lymnaea stagnalis and Aplysia californica. We
      found that [A10L,D14K]PnIA also distinguishes two alpha7-like anion-selective
      nAChR subtypes present on identified neurons of L. stagnalis: [D14K] mutation
      affected only slightly the potency of [A10L]PnIA to block nAChRs on neurons with
      low sensitivity to alpha-conotoxin ImI, but gave a 50-fold enhancement of
      blocking activity in cells with high sensitivity to ImI. Therefore, the
      introduction of an additional positive charge in the C-terminus of alpha
      conotoxins targeting some muscle or neuronal nAChRs made them more discriminative
      towards the respective nAChR subtypes. In the case of muscle-type alpha-conotoxin
      [D12K]SIA, the contribution of the Lys12 positive charge to enhanced affinity
      towards Torpedo nAChR was rationalized with the aid of computer modeling.

PMID- 16956366
TI  - The potent inhibitory activity of histone H1.2 C-terminal fragments on furin.
AB  - Many physiologically important proproteins, pathogenic bacterial exotoxins and
      viral envelope glycoproteins are activated by the proprotein convertase furin,
      which makes furin inhibitor a hot target for basic research and drug design.
      Although synthetic and bioengineered inhibitors of furin have been well
      characterized, its endogenous inhibitor has not been directly purified from
      mammalian tissues to date. In this study, three inhibitors were purified from the
      porcine liver by using a combination of chromatographic techniques, and
      identified to be the C-terminal truncated fragments with different sizes of
      histone H1.2. The gene of porcine histone H1.2 was cloned and sequenced, further
      confirming the determined sequences. These three C-terminal fragments inhibited
      furin with Ki values around 2 x 10(-7) m while the full-length histone H1.2
      inhibited it with a lesser activity, suggesting that the inhibitory activity
      relies on the C-terminal lysine-rich domain. Though the inhibition was temporary,
      these inhibitors were specific, and the reactive site of one C-terminal fragment
      was identified. A 36 amino acid peptide around the reactive site was synthesized,
      which could still inhibit furin with a Ki of 5.2 x 10(-7) m.

PMID- 16956367
TI  - Mycobacterium tuberculosis possesses a functional enzyme for the synthesis of
      vitamin C, L-gulono-1,4-lactone dehydrogenase.
AB  - The last step of the biosynthesis of L-ascorbic acid (vitamin C) in plants and
      animals is catalyzed by L-gulono-1,4-lactone oxidoreductases, which use both L
      gulono-1,4-lactone and L-galactono-1,4-lactone as substrates. L-gulono-1,4
      lactone oxidase is missing in scurvy-prone, vitamin C-deficient animals, such as
      humans and guinea pigs, which are also highly susceptible to tuberculosis. A
      blast search using the rat L-gulono-1,4-lactone oxidase sequence revealed the
      presence of closely related orthologs in a limited number of bacterial species,
      including several pathogens of human lungs, such as Mycobacterium tuberculosis,
      Pseudomonas aeruginosa, Burkholderia cepacia and Bacillus anthracis. The genome
      of M. tuberculosis, the etiologic agent of tuberculosis, encodes a protein
      (Rv1771) that shows 32% identity with the rat L-gulono-1,4-lactone oxidase
      protein. The Rv1771 gene was cloned and expressed in Escherichia coli, and the
      corresponding protein was affinity-purified and characterized. The FAD-binding
      motif-containing Rv1771 protein is a metalloenzyme that oxidizes L-gulono-1,4
      lactone (Km 5.5 mm) but not L-galactono-1,4-lactone. The enzyme has a
      dehydrogenase activity and can use both cytochrome c (Km 4.7 microm) and
      phenazine methosulfate as exogenous electron acceptors. Molecular oxygen does not
      serve as a substrate for the Rv1771 protein. Dehydrogenase activity was measured
      in cellular extracts of a Mycobacterium bovis BCG strain. In conclusion, M.
      tuberculosis produces a novel, highly specific L-gulono-1,4-lactone dehydrogenase
      (Rv1771) and has the capacity to synthesize vitamin C.

PMID- 16956368
TI  - A family of killer toxins. Exploring the mechanism of ADP-ribosylating toxins.
AB  - The ADP-ribosylating toxins (ADPRTs) are a family of toxins that catalyse the
      hydrolysis of NAD and the transfer of the ADP-ribose moiety onto a target. This
      family includes many notorious killers, responsible for thousands of deaths
      annually including: cholera, enterotoxic Escherichia coli, whooping cough,
      diphtheria and a plethora of Clostridial binary toxins. Despite their notoriety
      as pathogens, the ADPRTs have been extensively used as cellular tools to study
      and elucidate the functions of the small GTPases that they target. There are four
      classes of ADPRTs and at least one structure representative of each of these
      classes has been determined. They all share a common fold and several motifs
      around the active site that collectively facilitate the binding and transfer of
      the ADP-ribose moiety of NAD to their protein targets. In this review, we present
      an overview of the physiology and cellular qualities of the bacterial ADPRTs and
      take an in-depth look at the structural motifs that differentiate the different
      classes of bacterial ADPRTs in relation to their function.

PMID- 16956369
TI  - Therapeutic targeting of molecules involved in leukocyte-endothelial cell
      interactions.
AB  - Inflammation is traditionally viewed as a physiological reaction to tissue
      injury. Leukocytes contribute to the inflammatory response by the secretion of
      cytotoxic and pro-inflammatory compounds, by phagocytotic activity and by
      targeted attack of foreign antigens. Leukocyte accumulation in tissues is
      important for the initial response to injury. However, the overzealous
      accumulation of leukocytes in tissues also contributes to a wide variety of
      diseases, such as atherosclerosis, chronic inflammatory bowel disease, rheumatoid
      arthritis, multiple sclerosis, vasculitis, systemic inflammatory response
      syndrome, juvenile diabetes and psoriasis. Many therapeutic interventions target
      immune cells after they have already migrated to the site of inflammation. This
      review addresses different therapeutic strategies, used to reduce or prevent
      leukocyte-endothelial cell interactions and communication, in order to limit the
      progression of inflammatory diseases.

PMID- 16956370
TI  - Endothelial signalling events during leukocyte transmigration.
AB  - The notion that it takes two to tango is certainly true for leukocyte
      transendothelial migration. A growing pallet of leukocyte adhesion-induced
      signaling events in endothelial cells have been identified, mediating both short
      term (i.e. permeability) as well as long-term (i.e. regulation of transcription)
      effects. Efficient paracellular migration (i.e. through endothelial cell-cell
      junctions) requires both intracellular calcium and the actin cytoskeleton, but
      also involves small GTPases, reactive oxygen species and protein kinases. The
      alternative route of transcellular migration appears to depend on components such
      as caveolae and intermediate filaments. This minireview discusses our current
      knowledge on the regulation of leukocyte transmigration through endothelial
      signalling.

PMID- 16956371
TI  - Leukocyte adhesion deficiency II. Advances and open questions.
AB  - Leukocyte adhesion deficiency II (LAD II) belongs to a group of human congenital
      diseases in which the interactions of leukocytes with the vascular endothelium
      are strongly impaired. LAD II is based on a defect in the synthesis of
      fucosylated glycostructures. This leads to an immunodeficiency owing to the
      absence of functional selectin ligands and to strong psychomotor defects, as a
      result of as-yet unknown reasons. In this review we focused on the current
      controversies, and open questions that have arisen from recent studies on the
      genetic defect, therapy and the basis of psychomotor defects in LAD II.

PMID- 16956372
TI  - Selectins and glycosyltransferases in leukocyte rolling in vivo.
AB  - Leukocyte rolling is an important step for the successful recruitment of
      leukocytes into tissue and occurs predominantly in inflamed microvessels and in
      high endothelial venules of secondary lymphoid organs. Leukocyte rolling is
      mediated by a group of C-type lectins, termed selectins. Three different
      selectins have been identified - P-, E- and L-selectin - which recognize and bind
      to crucial carbohydrate determinants on selectin ligands. Among selectin ligands,
      P-selectin glycoprotein ligand-1 is the main inflammatory selectin ligand,
      showing binding to all three selectins under in vivo conditions. Functional
      relevant selectin ligands expressed on high endothelial venules of lymphoid
      tissue are less clearly defined at the protein level. However, high endothelial
      venule-expressed selectin ligands were instrumental in uncovering the crucial
      role of post-translational modifications for selectin ligand activity. Several
      glycosyltransferases, such as core 2 beta1,6-N-acetylglucosaminyltransferase-I,
      beta1,4-galactosyltransferases, alpha1,3-fucosyltransferases and alpha2,3
      sialyltransferases have been described to participate in the synthesis of core 2
      decorated O-glycan structures carrying the tetrasaccharide sialyl Lewis X, a
      carbohydrate determinant on selectin ligands with binding activity to all three
      selectins. In addition, modifications, such as carbohydrate or tyrosine
      sulfation, were also found to contribute to the synthesis of functional selectin
      ligands.

PMID- 16956374
TI  - Ca2+-binding allergens from olive pollen exhibit biochemical and immunological
      activity when expressed in stable transgenic Arabidopsis.
AB  - Employing transgenic plants as alternative systems to the conventional
      Escherichia coli, Pichia pastoris or baculovirus hosts to produce recombinant
      allergens may offer the possibility of having available edible vaccines in the
      near future. In this study, two EF-hand-type Ca2+-binding allergens from olive
      pollen, Ole e 3 and Ole e 8, were produced in transgenic Arabidopsis thaliana
      plants. The corresponding cDNAs, under the control of the constitutive CaMV 35S
      promoter, were stably incorporated into the Arabidopsis genome and encoded
      recombinant proteins, AtOle e 3 and AtOle e 8, which exhibited the molecular
      properties (i.e. MS analyses and CD spectra) of their olive and/or E. coli
      counterparts. Calcium-binding assays, which were carried out to assess the
      biochemical activity of AtOle e 3 and AtOle e 8, gave positive results. In
      addition, their mobilities on SDS/PAGE were according to the conformational
      changes derived from their Ca2+-binding capability. The immunological behaviour
      of Arabidopsis-expressed proteins was equivalent to that of the natural- and/or
      E. coli-derived allergens, as shown by their ability to bind allergen-specific
      rabbit IgG antiserum and IgE from sensitized patients. These results indicate
      that transgenic plants constitute a valid alternative to obtain allergens with
      structural and immunological integrity not only for scaling up production, but
      also to develop new kind of vaccines for human utilization.

PMID- 16956375
TI  - Effect of sublethal 6-hydroxydopamine on the response to subsequent oxidative
      stress in dopaminergic cells: evidence for preconditioning.
AB  - Exposure to sublethal stress can trigger endogenous protection against
      subsequent, higher levels of stress. We tested for this preconditioning
      phenomenon in a model of Parkinson's disease by applying 6-hydroxydopamine to the
      dopaminergic MN9D cell line. Exposure to sublethal concentrations of 6
      hydroxydopamine (5-10 microM) protected against the toxic effects of a subsequent
      exposure to a higher concentration (50 microM), as measured by the Hoechst assay
      for nuclear viability. This was accompanied by little or no protection against 6
      hydroxydopamine-induced lactate dehydrogenase release, decline in ATP, or
      reduction in (3)H-dopamine uptake. The antioxidant, N-acetyl cysteine (20 mM),
      when applied during preconditioning, abolished protection, as did the protein
      synthesis inhibitor, cycloheximide (0.2 microM). Preconditioning did not affect
      superoxide dismutase or glutathione peroxidase enzymes, or levels of heat shock
      protein-72. However, Bcl-2 protein levels rose with preconditioning.
      Preconditioning rapidly increased phosphorylation of kinases ERK1/2, Akt and JNK,
      and was abolished by pharmacological inhibitors of their activity. Finally,
      sublethal 6-hydroxydopamine preconditioned against the toxicity of proteasome
      inhibitor, MG-132 (1 microM). Thus, exposure of a dopaminergic cell line to
      sublethal oxidative stress can protect against additional oxidative stress due to
      translational and post-translational modifications, as well as confer 'cross
      tolerance' against a different insult, proteasome inhibition.

PMID- 16956376
TI  - Species-specific chemosignals evoke delayed excitation of the vomeronasal
      amygdala in freely-moving female rats.
AB  - Male rat chemosignals attract females and influence their reproductive status.
      Through the accessory olfactory bulb and its projection target, the posteromedial
      cortical nucleus of the amygdala (PMCo), species-specific chemosignals detected
      by the vomeronasal organ (VNO) may reach the hypothalamus. To test this
      hypothesis in vivo, behavioural activation and neurotransmitter release in the
      PMCo were simultaneously monitored in freely moving female oestrus rats exposed
      to either rat or mouse urinary stimuli, or to odorants. Plasma levels of the
      luteinizing hormone were subsequently monitored. All stimuli induced an immediate
      behavioural activation, but only species-specific chemosignals led to a delayed
      behavioural activation. This biphasic behavioural activation was accompanied by a
      VNO-mediated release of the excitatory amino acids, aspartate and glutamate, in
      the PMCo. The late behavioural and neurochemical activation was followed by an
      increase in the levels of circulating luteinizing hormone. In conclusion, these
      data show that only species-specific chemosignals induce a delayed behavioural
      activation and excitatory activation of the PMCo, which is dependent on an intact
      VNO.

PMID- 16956377
TI  - The nuclear GTPase Gsp1p can affect proper telomeric function through the Sir4
      protein in Saccharomyces cerevisiae.
AB  - The small Ras-like GTPase Ran/Gsp1p is a highly conserved nuclear protein
      required for the nucleocytoplasmic trafficking of macromolecules. Recent findings
      suggest that the Ran/Gsp1p pathway may have additional roles in several aspects
      of nuclear structure and function, including spindle assembly, nuclear envelope
      formation, nuclear pore complex assembly and RNA processing. Here, we provide
      evidence that Gsp1p can regulate telomeric function in Saccharomyces cerevisiae.
      We show that overexpression of PRP20, encoding the Gsp1p GDP/GTP nuclear exchange
      factor, specifically weakens telomeric silencing without detectably affecting
      nucleocytoplasmic transport. In addition to this silencing defect, we show that
      Rap1p and Sir3p delocalize from their normal telomeric foci. Interestingly, Gsp1p
      was found to interact genetically and physically with the telomeric component
      Sir4p. Taken together, these results suggest that the GSP1 pathway could regulate
      proper telomeric function in yeast through Sir4p.

PMID- 16956378
TI  - Deletion of the gliP gene of Aspergillus fumigatus results in loss of gliotoxin
      production but has no effect on virulence of the fungus in a low-dose mouse
      infection model.
AB  - Gliotoxin is a secondary metabolite produced by several fungi including the
      opportunistic human pathogen Aspergillus fumigatus. As gliotoxin exerts
      immunosuppressive effects in vitro and in vivo, a role as a virulence determinant
      in invasive aspergillosis has been discussed for a long time but evidence has not
      been provided until now. Here, by the use of different selection marker genes A.
      fumigatus knock-out strains were generated that are deficient for the non
      ribosomal peptide synthetase GliP, the putative key enzyme of the gliotoxin
      biosynthesis. Deletion of the gliP gene resulted in loss of gliotoxin production,
      as analysed by high performance liquid chromatography and tandem mass
      spectrometry. No differences in morphology or growth kinetics between wild-type
      and gliP-deletion strains were observed. In vitro, the culture supernatant of the
      gliP-deficient strains showed a reduced cytotoxic effect on both macrophage-like
      cells and T cell lines. In a low-dose murine infection model of invasive
      aspergillosis, gliotoxin was detected in the lung and absent when mice were
      infected with the gliP deletion strain. However, gliP deletion strains showed no
      difference in virulence compared with the corresponding wild-type strains. Taken
      together, the non-ribosomal peptide synthetase GliP is essential for gliotoxin
      production in A. fumigatus. Gliotoxin is not required for pathogenicity of the
      fungus in immunocompromised mice, despite the fact that a reduced cytotoxicity of
      the culture supernatant of gliP deletion strains was demonstrated.

PMID- 16956379
TI  - The Campylobacter jejuni PhosS/PhosR operon represents a non-classical phosphate
      sensitive two-component system.
AB  - The bacterial pathogen Campylobacter jejuni carries several putative two
      component signal transduction systems of unknown function. Here we report that
      the PhosS (Cj0889) and PhosR (Cj0890) proteins constitute a two-component system
      that is activated by phosphate limitation. Microarray analysis, real-time RT-PCR,
      and primer extension experiments indicated that this system regulates 12 genes
      (including the pstSCAB genes) present in three transcriptional units. Gel shift
      assays confirmed that recombinant PhosR protein bound DNA fragments containing
      the promoter regions upstream of these three transcriptional units. Although
      functionally similar, the PhosS/PhosR does not exhibit sequence homology with the
      classical PhoBR systems, has a different pho box (5'-GTTTCNAAAANGTTTC-3')
      recognized by the C. jejuni response regulator, and is not autoregulated. Because
      of these atypical properties, we designated the Cj0889-Cj0890 operon as the C.
      jejuni PhosS/PhosR system (phosphate sensor/phosphate response regulator) and the
      phosphate-regulated genes as the pho regulon of C. jejuni.

PMID- 16956380
TI  - Role of protein phosphatases 2C on tolerance to lithium toxicity in the yeast
      Saccharomyces cerevisiae.
AB  - Protein phosphatases 2C are a family of conserved enzymes involved in many
      aspects of the cell biology. We reported that, in the yeast Saccharomyces
      cerevisiae, overexpression of the Ptc3p isoform resulted in increased lithium
      tolerance in the hypersensitive hal3 background. We have found that the tolerance
      induced by PTC3 overexpression is also observed in wild-type cells and that this
      is most probably the result of increased expression of the ENA1 Na(+)-ATPase
      mediated by the Hog1 MAP kinase pathway. This effect does not require a
      catalytically active protein. Surprisingly, deletion of PTC3 (similarly to that
      of PTC2, PTC4 or PTC5) does not confer a lithium-sensitive phenotype, but
      mutation of PTC1 does. Lack of PTC1 in an ena1-4 background did not result in
      additive lithium sensitivity and the ptc1 mutant showed a decreased expression of
      the ENA1 gene in cells stressed with LiCl. In agreement, under these conditions,
      the ptc1 mutant was less effective in extruding Li(+) and accumulated higher
      concentrations of this cation. Deletion of PTC1 in a hal3 background did not
      exacerbate the halosensitive phenotype of the hal3 strain. In addition, induction
      from the ENA1 promoter under LiCl stress decreased similarly (50%) in hal3, ptc1
      and ptc1 hal3 mutants. Finally, mutation of PTC1 virtually abolishes the
      increased tolerance to toxic cations provided by overexpression of Hal3p. These
      results indicate that Ptc1p modulates the function of Ena1p by regulating the
      Hal3/Ppz1,2 pathway. In conclusion, overexpression of PTC3 and lack of PTC1
      affect lithium tolerance in yeast, although through different mechanisms.

PMID- 16956381
TI  - Nickel homeostasis in Escherichia coli - the rcnR-rcnA efflux pathway and its
      linkage to NikR function.
AB  - The nickel physiology of Escherichia coli is dominated by its Ni-Fe hydrogenase
      isozymes, which are expressed under anaerobic growth conditions. Hydrogenase
      activity in E. coli requires the NikABCDE nickel transporter, which is
      transcriptionally repressed by NikR in the presence of excess nickel. Recently, a
      nickel and cobalt-efflux protein, RcnA, was identified in E. coli. This study
      examines the effect of RcnA on nickel homeostasis in E. coli. Under nickel
      limiting conditions, deletion of rcnA increased NikR activity in vivo. Nickel and
      cobalt-dependent regulation of rcnA expression required the newly identified
      transcriptional repressor RcnR (formerly YohL). Deletion of rcnR results in
      constitutive rcnA expression and a corresponding decrease in NikR activity.
      Purified RcnR binds directly to the rcnA promoter DNA fragment and this
      interaction is inhibited by nickel and cobalt. Nickel accumulation is affected
      differently among deletion strains with impaired nickel homeostasis.
      Surprisingly, in low nickel growth conditions rcnA expression is required for
      nickel import via NikABCDE. The data support a model with two distinct pools of
      nickel ions in E. coli. NikR bridges these two pools by controlling the levels of
      the hydrogenase-associated pool based on the nickel levels in the second pool.

PMID- 16956383
TI  - PBP3 inhibition elicits adaptive responses in Pseudomonas aeruginosa.
AB  - Adaptive evolution depends on both the genetic variability in a population of
      organisms and the selection of the better adapted genotypes. However, for the
      fittest variants to be selected they must survive over a sufficient period under
      the new conditions. Bacteria are often exposed to different types of stress in
      nature, including antibiotics. We analysed the global expression profiles of the
      opportunistic pathogen Pseudomonas aeruginosa in response to ceftazidime, a PBP3
      inhibitor, at different concentrations and times. PBP3 inhibition exerts a global
      impact on the transcription of a large number of genes. From an adaptive
      perspective, it is noteworthy the induction of several SOS genes, as well as
      adaptation, protection and antibiotic resistance genes. Intriguingly,
      transcription of pyocin genes, previously described as SOS-regulated, was
      repressed upon PBP3 inhibition. Ciprofloxacin, an SOS inducer, produced
      transcriptional induction of pyocins. Our results indicate that: (i) the SOS
      responses resulting from treatments with these two antibiotics cause only
      partially overlapping transcription profiles; (ii) PBP3 and DNA-gyrase inhibition
      produce opposite effects on transcription of pyocin genes. Consequently,
      ceftazidime decreases ciprofloxacin toxicity; (iii) error-prone DNA-polymerase
      DinB is induced by PBP3 inhibition but not by DNA-gyrase inhibition; (iv) PBP3
      inhibition causes induced mutagenesis; (v) ceftazidime upregulates several
      antibiotic-resistance and adaptation genes; and (vi) ceftazidime concentrations
      thought previously to be lethal are not, as most cells treated with ceftazidime
      remain alive and recover their capacity to form colonies. Thus, transcriptional
      changes demonstrated in this work are likely to be adaptively relevant to cells
      that survive.

PMID- 16956382
TI  - PfCRT and the trans-vacuolar proton electrochemical gradient: regulating the
      access of chloroquine to ferriprotoporphyrin IX.
AB  - It is accepted that resistance of Plasmodium falciparum to chloroquine (CQ) is
      caused primarily by mutations in the pfcrt gene. However, a consensus has not yet
      been reached on the mechanism by which resistance is achieved. CQ-resistant (CQR)
      parasite lines accumulate less CQ than do CQ-sensitive (CQS) parasites. The CQR
      phenotype is complex with a component of reduced energy-dependent CQ uptake and
      an additional component that resembles energy-dependent CQ efflux. Here we show
      that the required energy input is in the form of the proton electrochemical
      gradient across the digestive vacuole (DV) membrane. Collapsing the DV proton
      gradient (or starving the parasites of glucose) results in similar levels of CQ
      accumulation in CQS and CQR lines. Under these conditions the accumulation of CQ
      is stimulated in CQR parasite lines but is reduced in CQS lines. Energy
      deprivation has no effect on the rate of CQ efflux from CQR lines implying that
      mutant PfCRT does not function as an efflux pump or active carrier. Using pfcrt
      modified parasite lines we show that the entire CQ susceptibility phenotype is
      switched by the single K76T amino acid change in PfCRT. The efflux of CQ in CQR
      lines is not directly coupled to the energy supply, consistent with a model in
      which mutant PfCRT functions as a gated channel or pore, allowing charged CQ
      species to leak out of the DV.

PMID- 16956384
TI  - Roles for the Drs2p-Cdc50p complex in protein transport and phosphatidylserine
      asymmetry of the yeast plasma membrane.
AB  - Drs2p, a P-type adenosine triphosphatase required for a phosphatidylserine (PS)
      flippase activity in the yeast trans Golgi network (TGN), was first implicated in
      protein trafficking by a screen for mutations synthetically lethal with arf1
      (swa). Here, we show that SWA4 is allelic to CDC50, encoding a membrane protein
      previously shown to chaperone Drs2p from the endoplasmic reticulum to the Golgi
      complex. We find that cdc50Delta exhibits the same clathrin-deficient phenotypes
      as drs2Delta, including delayed transport of carboxypeptidase Y to the vacuole,
      mislocalization of resident TGN enzymes and the accumulation of aberrant membrane
      structures. These trafficking defects precede appearance of cell polarity defects
      in cdc50Delta, suggesting that the latter are a secondary consequence of
      disrupting Golgi function. Involvement of Drs2p-Cdc50p in PS translocation
      suggests a role in restricting PS to the cytosolic leaflet of the Golgi and
      plasma membrane. Annexin V binding and papuamide B hypersensitivity indicate that
      drs2Delta or cdc50Delta causes a loss of plasma membrane PS asymmetry. However,
      clathrin and other endocytosis null mutants also exhibit a comparable loss of PS
      asymmetry, and studies with drs2-ts and clathrin (chc1-ts) conditional mutants
      suggest that loss of plasma membrane asymmetry is a secondary consequence of
      disrupting protein trafficking.

PMID- 16956386
TI  - Guarding the immune system: suppression of autoimmunity by CD4+CD25+
      immunoregulatory T cells.
AB  - CD4+CD25+Foxp3+ T cells (CD25+ T regulatory [Treg] cells) are a naturally
      occurring suppressor T-cell population that regulates a wide variety of immune
      responses. A major function of CD25+ Treg cells is to inhibit the activity of
      self-reactive T cells that can potentially cause autoimmune disease. This review
      examines the recent advances in CD25+ Treg cell biology, with particular focus on
      the thymic and peripheral development of CD25+ Treg cells, the signals that
      promote their expansion and maintenance in the periphery and the mechanism by
      which they mediate their suppressor activity in peripheral lymphoid tissues. An
      understanding of these issues is likely to facilitate the development of CD25+
      Treg-cell-based therapies for the treatment of autoimmune disease.

PMID- 16956387
TI  - CTL response compensation for the loss of an immunodominant class I-restricted
      HSV-1 determinant.
AB  - The T-cell response to even complex pathogens is often focused on only a handful
      of immunodominant determinants. Such narrow responses provoke a selective
      pressure that can drive the emergence of CTL escape variants, raising the
      question of whether a broader response, targeting multiple non-dominant peptides
      may be more beneficial. To examine the ability of the T-cell repertoire to
      respond to non-dominant determinants, we have investigated how mutating the
      dominant peptide in HSV affects the magnitude of the CD8+ T-cell response. We
      found that the CTL response to HSV lacking the dominant peptide was only modestly
      reduced compared with the wild-type virus and, surprisingly, this compensation
      occurred without any enhancement in the response to an established minor epitope.
      These findings are supportive of a malleable T-cell repertoire that can elicit
      strong responses to alternate, unknown determinants in the absence of the
      dominant response.

PMID- 16956385
TI  - Regulatory dissociation of Tctex-1 light chain from dynein complex is essential
      for the apical delivery of rhodopsin.
AB  - Post-Golgi to apical surface delivery in polarized epithelial cells requires the
      cytoplasmic dynein motor complex. However, the nature of dynein-cargo
      interactions and their underlying regulation are largely unknown. Previous
      studies have shown that the apical surface targeting of rhodopsin requires the
      dynein light chain, Tctex-1, which binds directly to both dynein intermediate
      chain (IC) and rhodopsin. In this report, we show that the S82E mutant of Tctex
      1, which mimics Tctex-1 phosphorylated at serine 82, has a reduced affinity for
      dynein IC but not for rhodopsin. Velocity sedimentation experiments further
      suggest that S82E is not incorporated into the dynein complex. The dominant
      negative effect of S82E causes rhodopsin mislocalization in polarized Madin-Darby
      canine kidney (MDCK) cells. The S82A mutant, which mimics dephosphorylated Tctex
      1, can be incorporated into dynein complex but is impaired in its release.
      Expression of S82A also causes disruption of the apical localization of rhodopsin
      in MDCK cells. Taken together, these results suggest that the dynein complex
      disassembles to release cargo due to the specific phosphorylation of Tctex-1 at
      the S82 residue and that this process is critical for the apical delivery of
      membrane cargoes.

PMID- 16956388
TI  - Reserpine-induced model of stress suppresses mucosal immunity.
AB  - Stress contributes significantly to the development of many diseases. In clinical
      studies, a strong correlation between depression and immune dysfunction has been
      shown. Our previous studies indicated that sympathetic innervation can regulate
      intestinal mucosal immunity through sympathetic synapses, but the mechanism in
      stress/depression-induced intestinal immune deficiency was unclear. Using a mouse
      model in which behavioural stress/depression is chemically induced by reserpine,
      it is found that there is a substantial deficiency of intestinal local humoral
      and particularly specific antibody response to the antigen stimulation in
      reserpine-treated group. No significant difference of CD4+, CD8+ or Mac1+ cells
      between reserpine-treated and control groups was detected in the intestine. This
      deficiency is closely correlated with stress/depression. A possible correlation
      between stress, cytokine secretion and humoral immunity in vivo is postulated.

PMID- 16956389
TI  - Cell surface markers of regulatory T cells are not associated with increased
      forkhead box p3 expression in blood CD4+ T cells from HIV-infected patients
      responding to antiretroviral therapy.
AB  - Regulatory T (Treg) cells may attenuate host immune responses to pathogens,
      including HIV and opportunistic pathogens in HIV-infected patients. Treated and
      untreated progressive HIV disease represent a range of immunological scenarios
      with potentially different roles for Treg cells. A cell surface marker to
      determine Treg cell numbers would assist in identifying situations where Treg
      cells are important. Here we show that levels of Foxp3 mRNA are increased in CD4+
      T cells from HIV-infected patients responding to antiretroviral therapy. However,
      the proportion of peripheral blood CD4+ and CD8+ T cells expressing CD25,
      neuropilin-1, glucocorticoid-induced TNF receptor and lymphocyte activation gene
      3 did not differ as a result of treated or untreated HIV infection when compared
      with HIV-seronegative controls. Hence, none of the putative Treg cell surface
      markers identified T-cell populations in peripheral blood that mirrored the
      effects of HIV infection and antiretroviral therapy on Foxp3 expression.

PMID- 16956390
TI  - Microglial cells from psychologically stressed mice as an accelerator of cerebral
      cryptococcosis.
AB  - Severe stress decreases the resistance of hosts exposed to microbial infections.
      As compared with two groups of control mice (normal mice, food-and-water-deprived
      mice [FWD mice]), restraint-stressed mice (RST mice) were shown to be greatly
      susceptible to intracerebral growth of Cryptococcus neoformans. The
      susceptibility of FWD mice to cerebral cryptococcosis increased to the level
      shown in RST mice, when these groups of mice were inoculated with microglial
      cells from the brains of RST mice. However, the susceptibility of FWD mice to
      cerebral cryptococcosis was not influenced by the adoptive transfer of microglial
      cells from normal mice or FWD mice. Microglial cells from RST mice produced CC
      chemokine ligand-2 (CCL-2/monocyte chemoattractant protein 1), but not microglial
      cells from FWD mice. The resistance of RST mice to cerebral cryptococcosis was
      improved to the extent shown in FWD mice, when they were treated with anti-CCL-2
      antibody. However, the susceptibility of normal mice and FWD mice to cerebral
      cryptococcosis increased to that shown in RST mice, when they were treated with
      rCCL-2. Microglial cells from RST mice were discriminated from the same cell
      preparations derived from FWD mice by their abilities to produce CCL-2, to
      phagocytize C. neoformans cells and to express Toll-like receptor 2. These
      results indicate that the resistance of RST mice to cerebral cryptococcosis is
      diminished by CCL-2 produced by microglial cells that are influenced by restraint
      stress.

PMID- 16956391
TI  - Membrane type 1-matrix metalloproteinase is involved in the migration of human
      monocyte-derived dendritic cells.
AB  - Dendritic cells (DC) are highly mobile APC. The trafficking of both immature and
      mature DC is crucial for their functions, which depends mainly on chemotactic
      attraction and matrix metalloproteinases (MMP) activity. MMP that are in a
      transmembrane form belong to membrane type (MT)-MMP, among which MT1-MMP has been
      shown to possess strong proteolytic activity that is capable of degrading
      extracellular matrix molecules. Although it is well established that MMP are zinc
      dependent endopeptidases that collectively degrade most components of the
      extracellular matrix, relatively little is known about MT-MMP-mediated matrix
      degradation during DC migration. In this study, we showed that MT1-MMP was
      expressed in human monocyte-derived immature and mature DC by semi-quantitative
      reverse transcription PCR and western blotting analyses. Moreover,
      immunofluorescence microscopic studies showed that MT1-MMP was expressed on the
      membrane surface of DC. Blocking of MT1-MMP activity greatly reduced the invasion
      capacity of immature DC in Matrigel, whereas mature DC mobility was not affected.
      Taken together, our results show a novel functional link between MT1-MMP and DC
      motility and suggest that MT1-MMP may play an important role in modulating the
      migration of immature DC.

PMID- 16956392
TI  - HIV-2 Protease resistance defined in yeast cells.
AB  - BACKGROUND: Inhibitors of the HIV-1 Protease currently used in therapeutic
      protocols, have been found to inhibit, although at higher concentrations, the HIV
      2 encoded enzyme homologue. Similar to observations in HIV-1 infected
      individuals, therapeutic failure has also been observed for some patients
      infected with HIV-2 as a consequence of the emergence of viral strains resistant
      to the anti-retroviral molecules. In order to be able to define the specific
      mutations in the Protease that confer loss of susceptibility to Protease
      Inhibitors, we set up an experimental model system based in the expression of the
      viral protein in yeast. RESULTS: Our results show that the HIV-2 Protease
      activity kills the yeast cell, and this process can be abolished by inhibiting
      the viral enzyme activity. Since this inhibition is dose dependent, IC50 values
      can be assessed for each anti-retroviral molecule tested. We then defined the
      susceptibility of HIV-2 Proteases to Protease Inhibitors by comparing the IC50
      values of Proteases from 7 infected individuals to those of a sensitive wild type
      laboratory adapted strain. CONCLUSION: This functional assay allowed us to show
      for the first time that the L90M substitution, present in a primary HIV-2
      isolate, modifies the HIV-2 Protease susceptibility to Saquinavir but not
      Lopinavir. Developing a strategy based on the proposed yeast expressing system
      will contribute to define amino acid substitutions conferring HIV-2 Protease
      resistance.

PMID- 16956393
TI  - A review of the evidence for the effectiveness of primary prevention
      interventions for hepatitis C among injecting drug users.
AB  - BACKGROUND: Hepatitis C (HCV) prevalence is most common amongst injecting drug
      users where up to 98% of the population can be infected despite a low prevalence
      of HIV. This review considers the evidence for the effectiveness of primary
      prevention interventions to reduce incidence or prevalence of hepatitis C.
      METHODS: Systematic review of the major electronic medical databases: Medline,
      EMBASE, PsycINFO, CINAHL and the Cochrane Library (Evidence Based Health). Either
      intervention or observational studies were included if they described an
      intervention targeting injecting drug using populations with the outcome to
      reduce either the prevalence or incidence of hepatitis C infection. RESULTS: 18
      papers were included in the final review from 1007 abstracts. Needle exchange
      programmes reduce the prevalence of HCV though prevalence remains high. Similarly
      the effectiveness of methadone maintenance treatment is only marginally effective
      at reducing HCV incidence. There is limited evidence evaluating either the
      effectiveness of behavioural interventions, bleach disinfectants, or drug
      consumption rooms. CONCLUSION: Primary prevention interventions have led to a
      reduction in HIV incidence, have been less effective at reducing HCV incidence.
      Global prevalence of HCV remains disturbingly high in injecting drug users. A
      robust response to the global health problem of HCV will require provision of new
      interventions. Behavioural interventions; distribution of bleach disinfectant;
      other injecting paraphernalia alongside sterile needle distribution; and
      evaluation of drug consumption rooms merit further expansion internationally and
      research activity to contribute to the emerging evidence base. Whilst the
      prevalence of HCV remains high, nevertheless many current interventions aimed at
      primary HCV prevention have been shown to be cost-effective due to their
      significant positive impact upon prevalence of HIV.

PMID- 16956394
TI  - RDMAS: a web server for RNA deleterious mutation analysis.
AB  - BACKGROUND: The diverse functions of ncRNAs critically depend on their
      structures. Mutations in ncRNAs disrupting the structures of functional sites are
      expected to be deleterious. RNA deleterious mutations have attracted wide
      attentions because some of them in cells result in serious disease, and some
      others in microbes influence their fitness. RESULTS: The RDMAS web server we
      describe here is an online tool for evaluating structural deleteriousness of
      single nucleotide mutation in RNA genes. Several structure comparison methods
      have been integrated; sub-optimal structures predicted can be optionally involved
      to mitigate the uncertainty of secondary structure prediction. With a user
      friendly interface, the web application is easy to use. Intuitive illustrations
      are provided along with the original computational results to facilitate quick
      analysis. CONCLUSION: RDMAS can be used to explore the structure alterations
      which cause mutations pathogenic, and to predict deleterious mutations which may
      help to determine the functionally critical regions. RDMAS is freely accessed via
      http://biosrv1.bmi.ac.cn/rdmas.

PMID- 16956395
TI  - Optimized detection of circulating anti-nuclear envelope autoantibodies by
      immunofluorescence.
AB  - BACKGROUND: Antinuclear antibodies are useful diagnostic tools in several
      autoimmune diseases. However, the routine detection of nuclear envelope
      autoantibodies using immunofluorescence (IF) is not always easy to perform in
      patients' sera because of the presence of autoantibodies to other nuclear and
      cytoplasmic components which could mask the characteristic rim-like pattern of
      nuclear envelope autoantibodies. This is particularly common in sera from
      patients with primary biliary cirrhosis (PBC), which generaly have high titres of
      anti-mitochondrial antibodies. Therefore, we have assayed a number of commercial
      slides and alternative fixation conditions to optimize the detection of anti
      nuclear envelope antibodies (ANEA) in PBC sera. METHODS: We have explored the
      presence of ANEA in 33 sera from patients with established PBC using three
      different Hep2 commercial slides and home-made slides with HeLa and Hep2 cells
      fixed with methanol, ethanol, 1% or 4% formaldehyde. RESULTS: We observed that
      the IF pattern was related to the cell type used (Hep2 or HeLa), the manufacturer
      and the cell fixation scheme. When both cell lines were fixed with 1%
      formaldehyde, the intensity of the cytoplasmic staining was considerably
      decreased regardless to the serum sample, whereas the prevalence of cytoplasmic
      autoantibodies was significantly lowered, as compared to any of the Hep2
      commercial slide and fixation used. In addition, the prevalence of ANEA was
      importantly increased in formaldehyde-fixed cells. CONCLUSION: Immunofluorescence
      using appropriately fixed cells represent an easy, no time-consuming and low cost
      technique for the routine screening of sera for ANEA. Detection of ANEA is shown
      to be more efficient using formaldehyde-fixed cells instead of commercially
      available Hep2 cells.

PMID- 16956396
TI  - Physical activity and medicine use: evidence from a population-based study.
AB  - BACKGROUND: Few studies have investigated the association between physical
      activity practice and medicine use; data from these studies are inconsistent. The
      aim of this study was to evaluate the association between level of physical
      activity and medicine use in adults aged 20 years or more. METHODS: A population
      based cross-sectional study was carried out in the first semester of 2002 in the
      urban area of Pelotas; a medium-sized Southern Brazilian city. Physical activity
      was assessed with the short version of the International Physical Activity
      Questionnaire. A physical activity score was created as the weekly time spent in
      moderate-intensity activities plus twice the weekly time spent in vigorous
      intensity activities. Medicine use in the 15 days prior to the interview was also
      assessed. Adjusted analyses taking into account the sampling design was carried
      out using Poisson regression. Wald tests for heterogeneity and linear trend were
      used to calculate significance. RESULTS: Out of the 3,182 individuals
      interviewed, 41% were not sufficiently active according to current physical
      activity guidelines. Only 34% of the subjects did not use medicines in the
      previous 15 days, and 18% used three or more drugs in the same period. Level of
      physical activity was inversely associated with the number of medicines used both
      in the crude and in the adjusted analyses. CONCLUSION: There are well-documented
      benefits of physical activity for several chronic diseases in the literature.
      Data from the present study suggest that medicine use is also positively affected
      by physical activity behavior.

PMID- 16956397
TI  - Renal lithiasis and nutrition.
AB  - Renal lithiasis is a multifactorial disease. An important number of etiologic
      factors can be adequately modified through diet, since it must be considered that
      the urine composition is directly related to diet. In fact, the change of
      inappropriate habitual diet patterns should be the main measure to prevent kidney
      stones. In this paper, the relation between different dietary factors (liquid
      intake, pH, calcium, phosphate, oxalate, citrate, phytate, urate and vitamins)
      and each type of renal stone (calcium oxalate monohydrate papillary, calcium
      oxalate monohydrate unattached, calcium oxalate dihydrate, calcium oxalate
      dihydrate/hydroxyapatite, hydroxyapatite, struvite infectious, brushite, uric
      acid, calcium oxalate/uric acid and cystine) is discussed.

PMID- 16956398
TI  - Antiepileptic drugs and bone metabolism.
AB  - Anti-epileptic medications encompass a wide range of drugs including
      anticonvulsants, benzodiazepines, enzyme inducers or inhibitors, with a variety
      effects, including induction of cytochrome P450 and other enzyme, which may lead
      to catabolism of vitamin D and hypocalcemia and other effects that may
      significantly effect the risk for low bone mass and fractures. With the current
      estimates of 50 million people worldwide with epilepsy together with the rapid
      increase in utilization of these medications for other indications, bone disease
      associated with the use of anti-epileptic medications is emerging as a serious
      health threat for millions of people. Nevertheless, it usually goes unrecognized
      and untreated. In this review we discuss the pathophysiologic mechanisms of bone
      disease associated with anti-epileptic use, including effect of anti-epileptic
      agents on bone turnover and fracture risk, highlighting various strategies for
      prevention of bone loss and associated fractures a rapidly increasing vulnerable
      population.

PMID- 16956399
TI  - Refuting phylogenetic relationships.
AB  - BACKGROUND: Phylogenetic methods are philosophically grounded, and so can be
      philosophically biased in ways that limit explanatory power. This constitutes an
      important methodologic dimension not often taken into account. Here we address
      this dimension in the context of concatenation approaches to phylogeny. RESULTS:
      We discuss some of the limits of a methodology restricted to verificationism, the
      philosophy on which gene concatenation practices generally rely. As an
      alternative, we describe a software which identifies and focuses on impossible or
      refuted relationships, through a simple analysis of bootstrap bipartitions,
      followed by multivariate statistical analyses. We show how refuting phylogenetic
      relationships could in principle facilitate systematics. We also apply our method
      to the study of two complex phylogenies: the phylogeny of the archaea and the
      phylogeny of the core of genes shared by all life forms. While many groups are
      rejected, our results left open a possible proximity of N. equitans and the
      Methanopyrales, of the Archaea and the Cyanobacteria, and as well the possible
      grouping of the Methanobacteriales/Methanoccocales and Thermosplasmatales, of the
      Spirochaetes and the Actinobacteria and of the Proteobacteria and firmicutes.
      CONCLUSION: It is sometimes easier (and preferable) to decide which species do
      not group together than which ones do. When possible topologies are limited,
      identifying local relationships that are rejected may be a useful alternative to
      classical concatenation approaches aiming to find a globally resolved tree on the
      basis of weak phylogenetic markers. REVIEWERS: This article was reviewed by Mark
      Ragan, Eugene V Koonin and J Peter Gogarten.

PMID- 16956400
TI  - Substance abuse prevention infrastructure: a survey-based study of the
      organizational structure and function of the D.A.R.E. program.
AB  - BACKGROUND: The only national drug abuse prevention delivery system that supports
      the rapid diffusion of new prevention strategies and includes uniform training
      and credentialing of instructors who are monitored for quality implementation of
      prevention programming is the Drug Abuse Resistance Education network (D.A.R.E.)
      linking community law enforcement to schools. Analysis of the organizational
      structure and function of D.A.R.E. provides an understanding of the essential
      parameters of this successful delivery system that can be used in the development
      of other types of national infrastructures for community-based prevention
      services. Information regarding organizational structure and function around
      funding issues, training, quality control and community relationships was
      gathered through telephone surveys with 50 state D.A.R.E. coordinators (including
      two major cities), focus groups with local D.A.R.E. officers and mentors, and
      interviews with national D.A.R.E. office staff. RESULTS: The surveys helped
      identify several strengths inherent in the D.A.R.E. program necessary for
      building a prevention infrastructure, including a well-defined organizational
      focus (D.A.R.E. America), uniform training and means for rapid dissemination
      (through its organized training structure), continuing education mechanisms
      (through the state and national conference and website), mechanisms for program
      monitoring and fidelity of implementation (formal and informal), branding and,
      for several states, predictable and consistent financing. Weaknesses of the
      program as currently structured include unstable funding and the failure to
      incorporate components for the continual upgrading of curricula reflecting
      research evidence and "principles of prevention". CONCLUSION: The D.A.R.E.
      organization and service delivery network provides a framework for the rapid
      dissemination of evidence-based prevention strategies. The major strength of
      D.A.R.E. is its natural affiliation to local law enforcement agencies through
      state coordinators. Through these affiliations, it has been possible for D.A.R.E.
      to become established nationally within a few years and internationally within a
      decade. Understanding how this structure developed and currently functions
      provides insights into how other such delivery systems could be developed.

PMID- 16956401
TI  - Ethnobotany of the Samburu of Mt. Nyiru, South Turkana, Kenya.
AB  - Traditional plant use is of extremely high importance in many societies, and
      prevalent in African communities. This knowledge is however dwindling rapidly due
      to changes towards a more Western lifestyle. The influence of modern tourism
      cannot be neglected in this context. This paper examines the plant use of the
      Samburu of the Mt. Nyiru area in Northern Kenya. The Samburu pastoralists of
      Kenya are still amongst the most traditional communities of the country and have
      retained most of their knowledge about the use of a large part of the plants in
      their environment for a wide variety of purposes. The results indicate that the
      local population has a very high knowledge of the plants in their surroundings,
      and attributes a purpose to a large percentage of the plants found. 448 plant
      species were collected, identified and their Samburu names and traditional uses
      recorded. 199 species were reported as of "no use". The high proportion of 249
      plant species however had some traditional use: The highest number (180 species)
      was used as fodder, followed by 80 species that had medicinal use. Firewood (59
      species), construction (42 species), tools (31 species), food (29 species) and
      ceremonial use (19 species) ranked far behind. Traditionally the Samburu
      attribute most illnesses to the effect of pollutants that block or inhibit
      digestion. This can include "polluted" food, contagion through sick people as
      well as witchcraft. In most cases the treatment of illness involves herbal
      purgatives to cleanse the patient. There are however frequent indications of
      plant use for common problems like wounds, parasites, body aches and burns. The
      change from a nomadic to a more sedentary lifestyle, often observed in other
      areas of the country, has affected the Samburu of remote Mt. Nyiru to a much
      lesser extent and did so far not lead to a major loss of traditional plant
      knowledge. However, overgrazing and over-exploitation of plant resources have
      already led to a decline of the plant material available.

PMID- 16956402
TI  - Open Access and beyond.
AB  - Uncensored exchange of scientific results hastens progress. Open Access does not
      stop at the removal of price and permission barriers; still, censorship and
      reading disabilities, to name a few, hamper access to information. Here, we
      invite the scientific community and the public to discuss new methods to
      distribute, store and manage literature in order to achieve unfettered access to
      literature.

PMID- 16956403
TI  - Distinct effects of rectum delineation methods in 3D-conformal vs. IMRT treatment
      planning of prostate cancer.
AB  - BACKGROUND: The dose distribution to the rectum, delineated as solid organ,
      rectal wall and rectal surface, in 3D conformal (3D-CRT) and intensity-modulated
      radiotherapy treatment (IMRT) planning for localized prostate cancer was
      evaluated. MATERIALS AND METHODS: In a retrospective planning study 3-field, 4
      field and IMRT treatment plans were analyzed for ten patients with localized
      prostate cancer. The dose to the rectum was evaluated based on dose-volume
      histograms of 1) the entire rectal volume (DVH) 2) manually delineated rectal
      wall (DWH) 3) rectal wall with 3 mm wall thickness (DWH(3)) 4) and the rectal
      surface (DSH). The influence of the rectal filling and of the seminal vesicles'
      anatomy on these dose parameters was investigated. A literature review of the
      dose-volume relationship for late rectal toxicity was conducted. RESULTS: In 3D
      CRT (3-field and 4-field) the dose parameters differed most in the mid-dose
      region: the DWH showed significantly lower doses to the rectum (8.7% +/- 4.2%)
      compared to the DWH(3) and the DSH. In IMRT the differences between dose
      parameters were larger in comparison with 3D-CRT. Differences were statistically
      significant between DVH and all other dose parameters and between DWH and DSH.
      Mean doses were increased by 23.6% +/- 8.7% in the DSH compared to the DVH in the
      mid-dose region. Furthermore, both the rectal filling and the anatomy of the
      seminal vesicles influenced the relationship between the dose parameters: a
      significant correlation of the difference between DVH and DWH and the rectal
      volume was seen in IMRT treatment. DISCUSSION: The method of delineating the
      rectum significantly influenced the dose representation in the dose-volume
      histogram. This effect was pronounced in IMRT treatment planning compared to 3D
      CRT. For integration of dose-volume parameters from the literature into clinical
      practice these results have to be considered.

PMID- 16956404
TI  - Modulation of humoral immune response to oral BCG vaccination by Mycobacterium
      bovis BCG Moreau Rio de Janeiro (RDJ) in healthy adults.
AB  - BACKGROUND: Oral administration of BCG was the route initially used by Calmette
      and Guerin, but was replaced by intradermal administration in virtually all
      countries after the Lubeck accident. However, Brazil continued to administer oral
      BCG Moreau RDJ, which was maintained until the mid-1970s when it was substituted
      by the intradermal route. Although BCG vaccination has been used in humans since
      1921, little is known of the induced immune response. The aim of this study was
      to analyse immunological responses after oral vaccination with M. bovis BCG
      Moreau RDJ. METHODS: This study in healthy volunteers has measured cellular and
      humoral aspects of the immunological response to oral M. bovis BCG Moreau RDJ in
      Rio de Janeiro, Brazil. T-cell trafficking and Th1 and Th2 cytokine responses are
      described, as well as isotype-specific antibody production using novel
      techniques. RESULTS: Oral immunisation has no adverse effects. We have shown that
      there are cellular and humoral immunological responses after oral immunisation.
      Oral revaccination does not induce a positive skin test in responsive individuals
      and multiple booster orally was able to induce modulation in humoral
      immunological responses (switch from IgG to IgA) in previously immunised subjects
      and incapable of inducing tolerance. In contrast, the cellular immune response
      does not differ between vaccinated individuals with positive and negative skin
      test reactions. CONCLUSION: All subjects, including those who did not respond to
      the skin test at study commencement, were capable of mounting humoral and
      cellular immune response to the antigens tested.

PMID- 16956405
TI  - Decreases in procalcitonin and C-reactive protein are strong predictors of
      survival in ventilator-associated pneumonia.
AB  - INTRODUCTION: This study sought to assess the prognostic value of the kinetics of
      procalcitonin (PCT), C-reactive protein (CRP) and clinical scores (clinical
      pulmonary infection score (CPIS), Sequential Organ Failure Assessment (SOFA)) in
      the outcome of ventilator-associated pneumonia (VAP) at an early time point, when
      adequacy of antimicrobial treatment is evaluated. METHODS: This prospective
      observational cohort study was conducted in a teaching hospital. The subjects
      were 75 patients consecutively admitted to the intensive care unit from October
      2003 to August 2005 who developed VAP. Patients were followed for 28 days after
      the diagnosis, when they were considered survivors. Patients who died before the
      28th day were non-survivors. There were no interventions. RESULTS: PCT, CRP and
      SOFA score were determined on day 0 and day 4. Variables included in the
      univariable logistic regression model for survival were age, Acute Physiology and
      Chronic Health Evaluation (APACHE) II score, decreasing DeltaSOFA, decreasing
      DeltaPCT and decreasing DeltaCRP. Survival was directly related to decreasing
      DeltaPCT with odds ratio (OR) = 5.67 (95% confidence interval 1.78 to 18.03),
      decreasing DeltaCRP with OR = 3.78 (1.24 to 11.50), decreasing DeltaSOFA with OR
      = 3.08 (1.02 to 9.26) and APACHE II score with OR = 0.92 (0.86 to 0.99). In a
      multivariable logistic regression model for survival, only decreasing DeltaPCT
      with OR = 4.43 (1.08 to 18.18) and decreasing DeltaCRP with OR = 7.40 (1.58 to
      34.73) remained significant. Decreasing DeltaCPIS was not related to survival (p
      = 0.59). There was a trend to correlate adequacy to survival. Fifty percent of
      the 20 patients treated with inadequate antibiotics and 65.5% of the 55 patients
      on adequate antibiotics survived (p = 0.29). CONCLUSION: Measurement of PCT and
      CRP at onset and on the fourth day of treatment can predict survival of VAP
      patients. A decrease in either one of these marker values predicts survival.

PMID- 16956406
TI  - An experimental model of rhinovirus induced chronic obstructive pulmonary disease
      exacerbations: a pilot study.
AB  - BACKGROUND: Acute exacerbations of COPD are a major cause of morbidity, mortality
      and hospitalisation. Respiratory viruses are associated with the majority of
      exacerbations but a causal relationship has not been demonstrated and the
      mechanisms of virus-induced exacerbations are poorly understood. Development of a
      human experimental model would provide evidence of causation and would greatly
      facilitate understanding mechanisms, but no such model exists. METHODS: We aimed
      to evaluate the feasibility of developing an experimental model of rhinovirus
      induced COPD exacerbations and to assess safety of rhinovirus infection in COPD
      patients. We carried out a pilot virus dose escalating study to assess the
      minimum dose of rhinovirus 16 required to induce experimental rhinovirus
      infection in subjects with COPD (GOLD stage II). Outcomes were assessed by
      monitoring of upper and lower respiratory tract symptoms, lung function, and
      virus replication and inflammatory responses in nasal lavage. RESULTS: All 4
      subjects developed symptomatic colds with the lowest dose of virus tested,
      associated with evidence of viral replication and increased pro-inflammatory
      cytokines in nasal lavage. These were accompanied by significant increases in
      lower respiratory tract symptoms and reductions in PEF and FEV1. There were no
      severe exacerbations or other adverse events. CONCLUSION: Low dose experimental
      rhinovirus infection in patients with COPD induces symptoms and lung function
      changes typical of an acute exacerbation of COPD, appears safe, and provides
      preliminary evidence of causation.

PMID- 16956408
TI  - Caveolin-1 interacts with the Gag precursor of murine leukaemia virus and
      modulates virus production.
AB  - BACKGROUND: Retroviral Gag determines virus assembly at the plasma membrane and
      the formation of virus-like particles in intracellular multivesicular bodies.
      Thereby, retroviruses exploit by interaction with cellular partners the cellular
      machineries for vesicular transport in various ways. RESULTS: The retroviral Gag
      precursor protein drives assembly of murine leukaemia viruses (MLV) at the plasma
      membrane (PM) and the formation of virus like particles in multivesicular bodies
      (MVBs). In our study we show that caveolin-1 (Cav-1), a multifunctional membrane
      associated protein, co-localizes with Gag in a punctate pattern at the PM of
      infected NIH 3T3 cells. We provide evidence that Cav-1 interacts with the matrix
      protein (MA) of the Gag precursor. This interaction is mediated by a Cav-1
      binding domain (CBD) within the N-terminus of MA. Interestingly, the CBD motif
      identified within MA is highly conserved among most other gamma-retroviruses.
      Furthermore, Cav-1 is incorporated into MLV released from NIH 3T3 cells.
      Overexpression of a GFP fusion protein containing the putative CBD of the
      retroviral MA resulted in a considerable decrease in production of infectious
      retrovirus. Moreover, expression of a dominant-negative Cav-1 mutant affected
      retroviral titres significantly. CONCLUSION: This study demonstrates that Cav-1
      interacts with MLV Gag, co-localizes with Gag at the PM and affects the
      production of infectious virus. The results strongly suggest a role for Cav-1 in
      the process of virus assembly.

PMID- 16956409
TI  - The use of free resources in a subscription-based digital library: a case study
      of the North Carolina AHEC Digital Library.
AB  - BACKGROUND: The North Carolina (NC) Area Health Education Center's (AHEC) Digital
      Library (ADL) is a web portal designed to meet the information needs of health
      professionals across the state by pulling together a set of resources from
      numerous different sources and linking a pool of users to only the resources for
      which they have eligibility. Although the ADL was designed with the primary
      purpose of linking health care professionals to a set of licensed resources, the
      ADL also contains a significant number of links to free resources. These
      resources are available to any ADL member logging into their ADL account and to
      guest visitors to the ADL. While there are regular assessments of the
      subscription resources in the ADL as to utility and frequency of use, up until
      this point there has been no systematic analysis of the use of the overall set of
      free resources. It was decided to undertake an examination of the usage of ADL
      free resources over a 6-month period to analyze the utility of these resources to
      both ADL members and guests. METHODS: Each time a resource is accessed through
      the ADL, it is logged in a table. This study used a SQL query to pull every free
      resource accessed between November 1, 2005 and April 30, 2006. An additional
      query also pulled the user information for each free resource accessed. Once the
      queries of the database were complete, the results were imported into an Excel
      spreadsheet and analyzed using basic descriptive statistics. RESULTS: The vast
      majority of resource use through the ADL is to licensed resources. There are 2056
      free resource URLs in the ADL, to which 1351 were linked out, meaning there was
      at least one link out to 65% of the free resources. The single most popular free
      resource was PubMed with 4803 link outs or nearly 20% of the total link outs to
      free resources. The breakdown of free resource use by different use groups
      indicates that the highest percentage of use of free resources was by guests
      followed by institutional affiliates and AHEC Faculty/Staff. The next 3 highest
      user groups accessing free resources are: paid members, preceptors, and
      residents. CONCLUSION: The only free resource capturing a significant number of
      link outs is the free link to PubMed. This reflects the importance placed on
      traditional medical literature searching by the ADL clinical user base.
      Institutional affiliates access free resources through the ADL with the second
      highest frequency of all the user groups. Finally, in analyzing use of free
      resources, it is important to note the overall limitations of this survey. While
      link outs are excellent indicators of frequency of use they do not provide any
      information about the ultimate usefulness of the resource being accessed. Further
      studies would need to examine not only the quantitative use of resources, but
      also their qualitative importance to the user.

PMID- 16956407
TI  - An exceptional horizontal gene transfer in plastids: gene replacement by a
      distant bacterial paralog and evidence that haptophyte and cryptophyte plastids
      are sisters.
AB  - BACKGROUND: Horizontal gene transfer (HGT) to the plant mitochondrial genome has
      recently been shown to occur at a surprisingly high rate; however, little
      evidence has been found for HGT to the plastid genome, despite extensive
      sequencing. In this study, we analyzed all genes from sequenced plastid genomes
      to unearth any neglected cases of HGT and to obtain a measure of the overall
      extent of HGT to the plastid. RESULTS: Although several genes gave strongly
      supported conflicting trees under certain conditions, we are confident of HGT in
      only a single case beyond the rubisco HGT already reported. Most of the conflicts
      involved near neighbors connected by long branches (e.g. red algae and their
      secondary hosts), where phylogenetic methods are prone to mislead. However, three
      genes--clpP, ycf2, and rpl36--provided strong support for taxa moving far from
      their organismal position. Further taxon sampling of clpP and ycf2 resulted in
      rejection of HGT due to long-branch attraction and a serious error in the
      published plastid genome sequence of Oenothera elata, respectively. A single new
      case, a bacterial rpl36 gene transferred into the ancestor of the cryptophyte and
      haptophyte plastids, appears to be a true HGT event. Interestingly, this rpl36
      gene is a distantly related paralog of the rpl36 type found in other plastids and
      most eubacteria. Moreover, the transferred gene has physically replaced the
      native rpl36 gene, yet flanking genes and intergenic regions show no sign of HGT.
      This suggests that gene replacement somehow occurred by recombination at the very
      ends of rpl36, without the level and length of similarity normally expected to
      support recombination. CONCLUSION: The rpl36 HGT discovered in this study is of
      considerable interest in terms of both molecular mechanism and phylogeny. The
      plastid acquisition of a bacterial rpl36 gene via HGT provides the first strong
      evidence for a sister-group relationship between haptophyte and cryptophyte
      plastids to the exclusion of heterokont and alveolate plastids. Moreover, the
      bacterial gene has replaced the native plastid rpl36 gene by an uncertain
      mechanism that appears inconsistent with existing models for the recombinational
      basis of gene conversion.

PMID- 16956410
TI  - Biological markers of lung injury before and after the institution of positive
      pressure ventilation in patients with acute lung injury.
AB  - BACKGROUND: Several biological markers of lung injury are predictors of morbidity
      and mortality in patients with acute lung injury (ALI). The low tidal volume lung
      protective ventilation strategy is associated with a significant decrease in
      plasma biomarker levels compared to the high tidal volume ventilation strategy.
      The primary objective of this study was to test whether the institution of lung
      protective positive pressure ventilation in spontaneously ventilating patients
      with ALI exacerbates pre-existing lung injury by using measurements of biomarkers
      of lung injury before and after intubation. MATERIALS AND METHODS: A prospective
      observational cohort study was conducted in the intensive care unit of a tertiary
      care university hospital. Twenty-five intubated, mechanically ventilated patients
      with ALI were enrolled. Physiologic data and serum samples were collected within
      6 hours before intubation and at two different time points within the first 24
      hours after intubation to measure the concentration of interleukin (IL)-6, IL-8,
      intercellular adhesion molecule 1 (ICAM-1), and von Willebrand factor (vWF). The
      differences in biomarker levels before and after intubation were analysed using
      repeated measures analysis of variance and a paired t test with correction for
      multiple comparisons. RESULTS: Before endotracheal intubation, all of the
      biological markers (IL-8, IL-6, ICAM-1, and vWF) were elevated in the
      spontaneously breathing patients with ALI. After intubation and the institution
      of positive pressure ventilation (tidal volume 7 to 8 ml/kg per ideal body
      weight), none of the biological markers was significantly increased at either an
      early (3 +/- 2 hours) or later (21 +/- 5 hours) time point. However, the levels
      of IL-8 were significantly decreased at the later time point (21 +/- 5 hours)
      after intubation. During the 24-hour period after intubation, the PaO2/FiO2
      (partial pressure of arterial oxygen/fraction of the inspired oxygen) ratio
      significantly increased and the plateau airway pressure significantly decreased.
      CONCLUSION: Levels of IL-8, IL-6, vWF, and ICAM-1 are elevated in spontaneously
      ventilating patients with ALI prior to endotracheal intubation. The institution
      of a lung-protective ventilation strategy with positive pressure ventilation does
      not further increase the levels of biological markers of lung injury. The results
      suggest that the institution of a lung-protective positive pressure ventilation
      strategy does not worsen the pre-existing lung injury in most patients with ALI.

PMID- 16956411
TI  - Peripheral blood complete remission after splenic irradiation in mantle-cell
      lymphoma with 11q22-23 deletion and ATM inactivation.
AB  - Mantle Cell Lymphoma (MCL) is a well-known histological and clinical subtype of B
      cell non-Hodgkin's Lymphomas. It is usually characterized by an aggressive
      disease course, presenting with advanced stage disease at diagnosis and with low
      response rates to therapy. However few cases of indolent course MCL have been
      described. We herein report a case of MCL with splenomegaly and peripheral blood
      involvement as main clinical features. The patient underwent moderate dose
      splenic radiation therapy and achieved spleen downsizing and peripheral blood
      complete remission. Splenic irradiation has been extensively used in the past as
      palliative treatment in several lymphoproliferative disorders and a systemic
      effect and sometimes peripheral blood complete remissions have been observed.
      Mainly advocated mechanisms responsible for this phenomenon are considered direct
      radiation-induced apoptotic cell death, immune modulation via proportional
      changes of lymphocyte subsets due to known differences in intrinsic
      radiosensitivity and a radiation-induced cytokine release. The peculiar intrinsic
      radiosensitivity pattern of lymphoid cells could probably be explained by well
      defined individual genetic and molecular features. In this context, among NHLs,
      MCL subtype has the highest rate of ATM (Ataxia Teleangiectasia Mutated)
      inactivation. While the ATM gene is thought to play a key-role in detecting
      radiation-induced DNA damage (especially Double Strand Breaks), recent in vitro
      data support the hypothesis that ATM loss may actually contribute to the
      radiosensitivity of MCL cells. ATM status was retrospectively investigated in our
      patient, with the tool of Fluorescence In Situ Hybridization, showing a complete
      inactivation of a single ATM allele secondary to the deletion of chromosomal
      region 11q22-23. The presence of this kind of cytogenetic aberration may be
      regarded in the future as a potential predictive marker of radiation response.

PMID- 16956412
TI  - Predicting the effect of missense mutations on protein function: analysis with
      Bayesian networks.
AB  - BACKGROUND: A number of methods that use both protein structural and evolutionary
      information are available to predict the functional consequences of missense
      mutations. However, many of these methods break down if either one of the two
      types of data are missing. Furthermore, there is a lack of rigorous assessment of
      how important the different factors are to prediction. RESULTS: Here we use
      Bayesian networks to predict whether or not a missense mutation will affect the
      function of the protein. Bayesian networks provide a concise representation for
      inferring models from data, and are known to generalise well to new data. More
      importantly, they can handle the noisy, incomplete and uncertain nature of
      biological data. Our Bayesian network achieved comparable performance with
      previous machine learning methods. The predictive performance of learned model
      structures was no better than a naive Bayes classifier. However, analysis of the
      posterior distribution of model structures allows biologically meaningful
      interpretation of relationships between the input variables. CONCLUSION: The
      ability of the Bayesian network to make predictions when only structural or
      evolutionary data was observed allowed us to conclude that structural information
      is a significantly better predictor of the functional consequences of a missense
      mutation than evolutionary information, for the dataset used. Analysis of the
      posterior distribution of model structures revealed that the top three strongest
      connections with the class node all involved structural nodes. With this in mind,
      we derived a simplified Bayesian network that used just these three structural
      descriptors, with comparable performance to that of an all node network.

PMID- 16956413
TI  - Genomic features of Bordetella parapertussis clades with distinct host species
      specificity.
AB  - BACKGROUND: The respiratory pathogen Bordetella parapertussis is a valuable model
      in which to study the complex phenotype of host specificity because of its unique
      two-species host range. One subset of strains, including the sequenced
      representative, causes whooping cough in humans, while other strains infect only
      sheep. The disease process in sheep is not well understood, nor are the genetic
      and transcriptional differences that might provide the basis for host specificity
      among ovine and human strains. RESULTS: We found 40 previously unknown genomic
      regions in an ovine strain of B. parapertussis using subtractive hybridization,
      including unique lipopolysaccharide genes. A microarray survey of the gene
      contents of 71 human and ovine strains revealed further differences, with 47
      regions of difference distinguishing the host-restricted subgroups. In addition,
      sheep and human strains displayed distinct whole-genome transcript abundance
      profiles. We developed an animal model in which sheep were inoculated with a
      sheep strain, human strain, or mixture of the two. We found that the ovine strain
      persisted in the nasal cavity for 12 to 14 days, while the human strain colonized
      at lower levels and was no longer detected by 7 days post-inoculation. The ovine
      strain induced less granulocyte infiltration of the nasal mucosa. CONCLUSION:
      Several factors may play a role in determining host range of B. parapertussis.
      Human- and ovine-associated strains have differences in content and sequence of
      genes encoding proteins that mediate host-pathogen contact, such as
      lipopolysaccharide and fimbriae, as well as variation in regulation of toxins,
      type III secretion genes, and other virulence-associated genes.

PMID- 16956414
TI  - Las noticias de Madrid (News from Madrid).
AB  - Over 5,000 participants attended the 10th International Conference on Alzheimer's
      Disease (ICAD) and Related Disorders in Madrid, Spain from July 15-20, 2006.
      Highlights of the conference included reports on brain imaging, the discovery of
      mutations in the progranulin gene that cause frontotemporal dementia, the finding
      that neuregulin-1 is a substrate for BACE1 and new interest in the connection
      between Alzheimer's disease and metabolic syndromes.

PMID- 16956415
TI  - Altered gene expression in asymptomatic SHIV-infected rhesus macaques (Macacca
      mulatta).
AB  - Simian-Human immunodeficiency virus is a chimeric virus which, in rhesus macaques
      (Macacca mulatta) closely imitates immunodeficiency virus infection in human
      (HIV). A relatively new way to study pathogenesis of viral infection is to study
      alterations in host gene expression induced by the virus. SHIV infection with
      certain strains does not result in clinical signs. We hypothesized that
      alterations in gene expression relating to the immune system would be present in
      SHIV-infected animals despite the lack of clinical signs. Splenic tissue from
      four adult male Indian-origin Rhesus monkeys serologically positive for non
      pathogenic SHIV 89.6 was processed by cDNA microarray analysis. Results were
      compared with the corresponding outcome using splenic tissues from four unexposed
      adult male Rhesus monkeys. Subsequent gene analysis confirmed statistically
      significant variations between control and infected samples. Interestingly, SHIV
      infected monkeys exhibited altered expression in genes related to apoptosis,
      signal transduction, T and B lymphocyte activation and importantly, to immune
      regulation. Although infected animals appeared asymptomatic, our study
      demonstrated that SHIV-infected monkeys cannot reliably be used in studies of
      other infectious agents as their baseline gene expression differs from that of
      normal Rhesus monkeys. The gene expression differences in SHIV-infected animals
      relative to uninfected animals offer additional clues to the pathogenesis of
      altered immune function in response to secondary infection.

PMID- 16956416
TI  - Correction: genetic algorithm learning as a robust approach to RNA editing site
      site prediction.
AB  - After the publication of [1], we were alerted to an error in our data. The error
      was an one-off miscalculation in the extraction of position information for our
      set of true negatives. Our data set should have used randomly selected non-edited
      cytosines (C) as true negatives, but the data generation phase resulted in a set
      of nucleotides that were each one nucleotide downstream of known, unedited
      cytosines. The consequences of this error are reflected in changes to our
      results, although the general conclusions presented in our original publication
      remain largely unchanged.

PMID- 16956417
TI  - Role of the employment status and education of mothers in the prevalence of
      intestinal parasitic infections in Mexican rural schoolchildren.
AB  - BACKGROUND: Intestinal parasitic infections are a public health problem in
      developing countries such as Mexico. As a result, two governmental programmes
      have been implemented: a) "National Deworming Campaign" and b) "Opportunities"
      aimed at maternal care. However, both programmes are developed separately and
      their impact is still unknown. We independently investigated whether a variety of
      socio-economic factors, including maternal education and employment levels, were
      associated with intestinal parasite infection in rural school children. METHODS:
      This cross-sectional study was conducted in 12 rural communities in two Mexican
      states. The study sites and populations were selected on the basis of the
      following traits: a) presence of activities by the national administration of
      albendazole, b) high rates of intestinal parasitism, c) little access to medical
      examination, and d) a population having less than 2,500 inhabitants. A total of
      507 schoolchildren (mean age 8.2 years) were recruited and 1,521 stool samples
      collected (3 per child). Socio-economic information was obtained by an oral
      questionnaire. Regression modelling was used to determine the association of
      socio-economic indicators and intestinal parasitism. RESULTS: More than half of
      the schoolchildren showed poliparasitism (52%) and protozoan infections (65%).
      The prevalence of helminth infections was higher in children from Oaxaca (53%)
      than in those from Sinaloa (33%) (p < 0.0001). Giardia duodenalis and Hymenolepis
      nana showed a high prevalence in both states. Ascaris lumbricoides, Trichuris
      trichiura and Entamoeba hystolitica/dispar showed low prevalence. Children from
      lower-income families and with unemployed and less educated mothers showed higher
      risk of intestinal parasitism (odds ratio (OR) 6.0, 95% confidence interval (CI)
      1.6-22.6; OR 4.5, 95% CI 2.5-8.2; OR 3.3, 95% CI 1.5-7.4 respectively).
      Defecation in open areas was also a high risk factor for infection (OR 2.4, 95%
      CI 2.0-3.0). CONCLUSION: Intestinal parasitism remains an important public health
      problem in Sinaloa (north-western Mexico) and Oaxaca (south-eastern Mexico).
      Lower income, defecation in open areas, employment status and a lower education
      level of mothers were the significant factors related to these infections. We
      conclude that mothers should be involved in health initiatives to control
      intestinal parasitism in Mexico.

PMID- 16956418
TI  - Long-term cyclical in vivo loading increases cartilage proteoglycan content in a
      spatially specific manner: an infrared microspectroscopic imaging and polarized
      light microscopy study.
AB  - Understanding the changes in collagen and proteoglycan content of cartilage due
      to physical forces is necessary for progress in treating joint disorders,
      including those due to overuse. Physical forces in the chondrocyte environment
      can affect the cellular processes involved in the biosynthesis of extracellular
      matrix. In turn, the biomechanical properties of cartilage depend on its collagen
      and proteoglycan content. To understand changes due to physical forces, this
      study examined the effect of 80 cumulative hours of in vivo cyclical joint
      loading on the cartilage content of proteoglycan and collagen in the rabbit
      metacarpophalangeal joint. The forepaw digits of six anesthetized New Zealand
      White adult female rabbits were repetitively flexed at 1 Hz with an estimated
      joint contact pressure of 1 to 2 MPa. Joints were collected from loaded and
      contralateral control specimens, fixed, decalcified, embedded, and thin
      sectioned. Sections were examined under polarized light microscopy to identify
      and measure superficial and mid zone thicknesses of cartilage. Fourier Transform
      Infrared microspectroscopy was used to measure proteoglycan and collagen contents
      in the superficial, mid, and deep zones. Loading led to an increase in
      proteoglycan in the cartilage of all six rabbits. Specifically, there was a 46%
      increase in the cartilage deep zone (p = 0.003). The collagen content did not
      change with loading. Joint loading did not change the superficial and mid zone
      mean thicknesses. We conclude that long-term (80 cumulative hours) cyclical in
      vivo joint loading stimulates proteoglycan synthesis. Furthermore, stimulation is
      localized to cartilage regions of high hydrostatic pressure. These data may be
      useful in developing interventions to prevent overuse injuries or in developing
      therapies to improve joint function.

PMID- 16956420
TI  - Knowledge of vitamin D and perceptions and attitudes toward sunlight among
      Chinese middle-aged and elderly women: a population survey in Hong Kong.
AB  - BACKGROUND: Physical and biological risk factors for vitamin D inadequacy are
      known; however, cultural- and population-specific behaviours and attitudes that
      influence these risk factors, particularly among Asian people, are less well
      documented. To understand more about prevailing attitudes and behaviour toward
      sunlight and knowledge of vitamin D among a population at greater risk of
      impaired vitamin D status, poor bone health and osteoporosis, we conducted a
      telephone interview survey of 547 middle-aged and elderly Chinese women living in
      Hong Kong. METHODS: All telephone interviews were conducted using the Computer
      Assisted Telephone Technique and target respondents were selected by random
      sampling. Interviews were conducted in Cantonese and eighteen main questions were
      asked pertaining to personal characteristics, perceptions, attitudes and
      behaviour toward sunlight, and knowledge about vitamin D. RESULTS: The survey
      results showed that 62.3% (n = 341) did not like going in the sun and 66.7% of
      respondents spent an average of 6-10 hours indoors, between 6:30 am and 7:00 pm,
      during weekdays. However, 58% of people thought that they had enough exposure to
      sunlight. The majority had heard of vitamin D, but knowledge about the role and
      sources of vitamin D was low. Among those who knew that sunlight was a source of
      vitamin D, the majority spent less than 1 h in the sun in the past week (76.4% vs
      23.6%, < 1 h in the sun in the past week vs > 1 h in the sun in the past week,
      chi-square p < 0.05). There were significantly more users of sunscreen products
      (75.5% vs 53.0%, p < 0.0001, sunscreen users vs non-users) and parasols (68.4% vs
      43.7%, p < 0.0001, parasol users vs non-users) among respondents who knew that
      vitamin D was good for bone health and that sunlight was a source of vitamin D.
      Age, occupation, subjects who liked going in the sun were factors associated with
      awareness of vitamin D but age was the only predictive factor for giving correct
      answers to the actions and sources of vitamin D. CONCLUSION: The survey revealed
      considerable ignorance and confusion about the role of sunlight in vitamin D
      production, and the function and sources of vitamin D. Attitudes and behaviour
      toward sunlight were largely negative and many took measures to avoid sunlight,
      particularly among younger (middle-aged) women who had good awareness of vitamin
      D.

PMID- 16956421
TI  - Baroreflex increases correlation and coherence of muscle sympathetic nerve
      activity (SNA) with renal and cardiac SNAs.
AB  - Despite accumulating data of muscle sympathetic nerve activity (SNA) measured by
      human microneurography, whether neural discharges of muscle SNA correlates and
      coheres with those of other SNAs controlling visceral organs remains unclear.
      Further, how the baroreflex control of SNA affects the relations between these
      SNAs remains unknown. In urethane and alpha-chloralose anesthetized, vagotomized,
      and aortic-denervated rabbits, we recorded muscle SNA from the tibial nerve using
      microneurography and simultaneously recorded renal and cardiac SNAs. After
      isolating the carotid sinuses, we produced a baroreflex closed-loop condition by
      matching the isolated intracarotid sinus pressure (CSP) with systemic arterial
      pressure (CLOSE). We also fixed CSP at operating pressure (FIX) or altered CSP
      widely (WIDE: operating pressure +/- 40 mmHg). Under these conditions, we
      calculated time-domain and frequency-domain measures of the correlation between
      muscle SNA and renal or cardiac SNAs. At CLOSE, muscle SNA resampled at 1 Hz
      correlated with both renal (r(2) = 0.71 +/- 0.04, delay = 0.10 +/- 0.004 s) and
      cardiac SNAs (r(2) = 0.58 +/- 0.03, delay = 0.13 +/- 0.004 s) at optimal delays.
      Moreover,muscle SNA at CLOSE strongly cohered with renal and cardiac
      SNAs(coherence >0.8) at the autospectral peak frequencies, and weakly (0.4-0.5)
      at the remaining frequencies. Increasing the magnitude of CSP change from FIX to
      CLOSE and further to WIDE resulted in corresponding increases in correlation and
      coherence functions at nonpeak frequencies, and the coherence functions at peak
      frequencies remained high (>0.8). In conclusion, muscle SNA correlates and
      coheres approximately with renal and cardiac SNAs under closed-loop baroreflex
      conditions. The arterial baroreflex is capable of potently homogenizing neural
      discharges of these SNAs by modulating SNA at the nonpeak frequencies of SNA
      autospectra.

PMID- 16956419
TI  - Over-expression of AhR (aryl hydrocarbon receptor) induces neural differentiation
      of Neuro2a cells: neurotoxicology study.
AB  - BACKGROUND: Dioxins and related compounds are suspected of causing neurological
      disruption in human and experimental animal offspring following perinatal
      exposure during development and growth. The molecular mechanism(s) of the actions
      in the brain, however, have not been fully investigated. A major participant in
      the process of the dioxin-toxicity is the dioxin receptor, namely the aryl
      hydrocarbon receptor (AhR). AhR regulates the transcription of diverse genes
      through binding to the xenobiotic-responsive element (XRE). Since the AhR has
      also been detected in various regions of the brain, the AhR may play a key role
      in the developmental neurotoxicity of dioxins. This study focused on the effect
      of AhR activation in the developing neuron. METHODS: The influence of the AhR on
      the developing neuron was assessed using the Neuro2a-AhR transfectant. The
      undifferentiated murine neuroblastoma Neuro2a cell line (ATCC) was stably
      transfected with AhR cDNA and the established cell line was named N2a-Ralpha. The
      activation of exogenous AhR in N2a-Ralpha cells was confirmed using RNAi, with si
      AhR suppressing the expression of exogenous AhR. The neurological properties of
      N2a-Ralpha based on AhR activation were evaluated by immunohistochemical analysis
      of cytoskeletal molecules and by RT-PCR analysis of mRNA expression of
      neurotransmitter-production related molecules, such as tyrosine hydroxylase (TH).
      RESULTS: N2a-Ralpha cells exhibited constant activation of the exogenous AhR.
      CYP1A1, a typical XRE-regulated gene, mRNA was induced without the application of
      ligand to the culture medium. N2a-Ralpha cells exhibited two significant
      functional features. Morphologically, N2a-Ralpha cells bore spontaneous neurites
      exhibiting axon-like properties with the localization of NF-H. In addition, cdc42
      expression was increased in comparison to the control cell line. The other is the
      catecholaminergic neuron-like property. N2a-Ralpha cells expressed tyrosine
      hydroxylase (TH) mRNA as a functional marker of catecholaminergic
      neurotransmitter production. Thus, exogenous AhR induced catecholaminergic
      differentiation in N2a-Ralpha cells. CONCLUSION: The excessive activation of AhR
      resulted in neural differentiation of Neuro2a cells. This result revealed that
      dioxins may affect the nervous system through the AhR-signaling pathway.
      Activated AhR may disrupt the strictly regulated brain formation with irregular
      differentiation occurring rather than cell death.

PMID- 16956422
TI  - The antiquity of psoriatic arthritis.

PMID- 16956423
TI  - Ultrasound imaging for the rheumatologist IV. Ultrasonography of the knee.
AB  - Ultrasound examination of the knee is particularly useful in the detection of
      synovitis, early degenerative changes within the articular cartilage of the
      femoral condyles, calcifications within the articular cartilage layer and
      menisci, bursitis, and popliteal cysts. Also, important anatomical information
      about the structural integrity of the supporting tissues around the knee can be
      obtained by ultrasound in patients presenting with 'knee pain'. We review the
      available evidence about the use of ultrasound in knee examination, provide
      information on the technical equipment and scanning methods and discuss the still
      controversial issues.

PMID- 16956424
TI  - Does rofecoxib increase TNF-alpha levels?
AB  - OBJECTIVE: Rofecoxib (Vioxx), the first COX-2 selective non-steroidal anti
      inflammatory drug (NSAID), was recently withdrawn from the market due to the
      increased risk of acute myocardial infarction. The precise mechanism responsible
      for this phenomenon still remains unknown. Tumor necrosis factor alpha (TNF
      alpha) is a cytokine, possibly most responsible for mortality in patients with
      acute myocardial infarction. However, this study was designed to study possible
      effects of rofecoxib on the level of TNF-alpha by using MSU crystal induced
      inflammation in the rat subcutaneous air pouch model. METHODS: Rat subcutaneous
      air pouches were produced and examinations commenced 6 days later. Control groups
      received only MSU crystals, or no crystals or drugs. To begin with, rofecoxib (30
      mg/kg), indomethacin (20 mg/kg) or diclofenac (3 mg/kg) were administered to
      groups of 5 rats each. Thirty minutes later, MSU crystals were injected into air
      pouches, except for the negative control group. Twenty-four hours later, the rats
      were sacrificed for aspiration of fluid and for the dissection of pouch walls to
      determine leukocyte counts, pouch wall histology, and to assay IL-10 and TNF
      alpha. RESULTS: Intra-pouch injection of MSU crystals, compared to non-injected
      pouches, caused an increase in white blood cell count (WBC) (30 +/- 44.7 versus
      4508 +/- 792.3 cells/mm3), in the numbers of pouch wall vessels (vascular index)
      (4.8 +/- 0.3 versus 11.4 +/- 1.5 vessels/high-power field) and in TNF-alpha (50.0
      +/- 13.4 versus 70.34 +/- 20.9 ng/mL), but not in interleukin-10 (IL-10) (60.6 +/
      63.0versus 61.48 +/- 7.1). WBC and vascular index were significantly reduced in
      all study groups compared to the control group (p < 0.05). Levels of TNF- in
      fluids were unexpectedly and significantly (p < 0.05) increased in all cases. The
      highest level of TNF-alpha was found in the rofecoxib group. In contrast to TNF
      alpha, IL-10 levels were significantly (p < 0.05) decreased in all three drug
      groups. Indomethacin tended to suppress inflammation more effectively. However,
      there was no significant difference between the groups for IL-10 (p > 0.05).
      CONCLUSION: All three NSAIDs exhibited anti-inflammatory activity against MSU
      crystal induced inflammation. The difference in anti-inflammatory effects of
      these three non-steroidal drugs is seen not only in the anti-inflammatory effect
      on MSU induced inflammation but also in the nature of the effects. Refocoxib
      tended to increase the TNF-alpha level. Whether increased TNF-alpha levels can
      help explain the side effect of COX-2 specific inhibitors still requires further
      studies.

PMID- 16956425
TI  - Effects of dexamethasone and celecoxib on calcium homeostasis and expression of
      cyclooxygenase-2 mRNA in MG-63 human osteosarcoma cells.
AB  - OBJECTIVE: Glucocorticoids and selective COX-2 inhibitors are potent anti
      inflammatory agents. They are also suggested to influence bone physiology and
      remodeling. Here we searched for effects of dexamethasone and celecoxib on
      crucial parameters of bone physiology that could be therapeutically relevant.
      METHODS: The human osteosarcoma cell line MG-63 was used to measure effects of
      these drugs on (i) intracellular calcium concentration ([Ca2+]i) using a
      microfluorometric technique, (ii) alkaline phosphatase and osteocalcin levels
      (EIA) and (iii) the expression of cox-2 mRNA (quantitative real time PCR).
      Measurements were performed in Vitamine D-incubated quiescent cells and in cells
      stimulated with TNF-alpha and IL-1beta. RESULTS: We found the cytokine
      stimulation to increase [Ca2+]i which was prevented by dexamethasone already
      after 30 min and still after 48 h. Dexamethasone was without any effect on
      [Ca2+]i in quiescent cells. Celecoxib had no measurable short-term or long-term
      effects neither in quiescent nor in stimulated cells. Vitamin D stimulated the
      expression of cox-2 mRNA which was further enhanced by TNF-alpha/IL-1beta.
      Dexamethasone did not have any measurable effects on COX-2 expression after 30
      min, but a pronounced inhibition was seen after 48 h. In contrast, celecoxib had
      no effect on COX-2 expression. Neither of the drugs had any effect on the
      secretion of alkaline phosphatase and osteocalcin. CONCLUSION: We found
      dexamethasone to inhibit the [Ca2+]i increase in MG-63 cells following
      stimulation and to reduce considerably COX-2 expression via the genomic pathway.
      In contrast, celecoxib did not show any measurable short-term or long-term
      effects on the parameters of bone physiology measured.

PMID- 16956426
TI  - Influence of anti-TNF-alpha infliximab therapy on adhesion molecules associated
      with atherogenesis in patients with rheumatoid arthritis.
AB  - OBJECTIVE: Chronic systemic inflammation plays a pivotal role in the development
      of atherosclerosis in rheumatoid arthritis (RA). Soluble (s) adhesion molecules
      were found significantly increased in RA patients with active disease. Since
      increased levels of some adhesion molecules were closely linked to the
      development of endothelial dysfunction and atherosclerosis and administration of
      anti-TNF-alpha-infliximab resulted in a rapid and dramatic improvement of
      endothelial function in long-term infliximab treated RA patients, we assessed
      whether infusion of the chimeric anti-TNF-alpha infliximab might also yield a
      rapid and favorable effect on serum levels of soluble adhesion molecules in RA
      patients periodically treated with this drug because of severe disease. METHODS:
      We recruited patients with RA refractory to conventional therapy seen over a
      period of 2 months at Hospital Xeral-Calde, Lugo, Spain, who were on periodical
      treatment with infliximab for at least 14 weeks. Blood samples for determination
      of sICAM-1, sICAM-3, sVCAM-1, sE-selectin, and sP-selectin levels by ELISA were
      taken immediately before and after infliximab infusion. RESULTS: Thirty-four RA
      patients (25 women; mean age: 55.4 years; mean DAS28: 4.27) fulfilled the
      inclusion criteria. Following infliximab infusion a reduction of the overall mean
      values of the five adhesion molecules was observed. However, when a Wilcoxon
      signed-rank test was used, only significant differences for sICAM-3 and sP
      selectin were observed. In this regard, sICAM-3 and sP-selectin levels fell in 26
      (77%) and 28 (82%) of the 34 patients. CONCLUSION: Our study confirms a rapid and
      beneficial effect of infliximab infusion on expression of some adhesion molecules
      in RA patients treated periodically with this anti-TNF-alpha monoclonal antibody
      because of severe disease.

PMID- 16956427
TI  - Outcome of patients with scleroderma admitted to intensive care unit. A report of
      nine cases.
AB  - OBJECTIVE: Patients with systemic rheumatic disease constitute a small percentage
      of admissions to the medical intensive care units (ICUs). Systemic sclerosis
      (SSc) is one of the rheumatic diseases that together with secondary complications
      may lead to a critical illness requiring hospitalization in the ICU. We present
      the features, clinical course and outcome of critically ill patients with
      scleroderma that were admitted to the ICU. METHODS: The medical records of nine
      patients with diagnosis of scleroderma (8 female, 1 male), admitted to the
      intensive care unit of Sheba Medical Center during the 11-year interval between
      1991 and 2002, were reviewed. RESULTS: The mean age of the patients at the time
      of admission to the ICU was 48 +/- 13 [SD] years. The mean duration of SSc from
      diagnosis to the ICU admission was 8 +/- 8 years. Six patients had diffuse SSc,
      two patients had limited SSc and one patient had juvenile diffuse morphea. The
      main reasons for admission to the ICU were: infection/ septic syndrome (n = 4),
      scleroderma renal crisis (SRC) with pulmonary congestion (n = 2), acute renal
      failure associated with diffuse alveolar hemorrhage namely scleroderma- pulmonary
      - renal syndrome (SPRS) (n = 1), iatrogenic pericardial tamponade (n = 1),
      mesenteric ischemia (n = 1). The patients had high severity illness score (mean
      APACHE II 25 +/- 3). Eight out of nine patients (89%) that were admitted to the
      ICU died during the hospitalization, six (66.6%) of them died in the ICU. Septic
      complications as the main cause of death were determined in five patients
      (62.5%), while four of them had pneumonia and acute respiratory failure along
      with underlying severe pulmonary fibrosis. Lungs and kidneys were the most common
      severely affected organs by SSc in our patients. CONCLUSION: The outcome of
      scleroderma patients admitted to the ICU was extremely poor. Infectious
      complication was the most common cause of death in our patients. Although
      infections are treatable, the high mortality rate for this group of patients was
      dependent on the severity of the underlying visceral organ involvement,
      particularly severe pulmonary fibrosis. The severity of this involvement is a
      poor outcome predictor. An early diagnosis and an appropriate treatment of such
      complications may help to reduce the mortality in scleroderma patients.

PMID- 16956428
TI  - Homocysteine enhances cytokine production in cultured synoviocytes from
      rheumatoid arthritis patients.
AB  - OBJECTIVE: Hyperhomocysteinemia is commonly observed in Rheumatoid Arthritis (RA)
      patients, thus putatively accounting in part for the high rate of cardiovascular
      events in these subjects. Homocysteine (Hcy) is known to exert a pro-inflammatory
      effect putatively contributing to the progression of atherosclerotic lesions by
      cytokine production from several vascular cell-types. In order to evaluate the
      possibility that Hcy may play a direct pro-inflammatory activity also in the
      joints of RA patients, we investigated: (i) the joint concentration of Hcy, and
      (ii) the effect of Hcy on cytokine production by unstimulated and IL-1beta
      stimulated human RA cultured synoviocytes. METHODS: In 5 RA and 5 controls
      subjects, Hcy was measured in the blood and knee synovial fluid, and specimens of
      synovial tissue were taken to obtain cell cultures. Cultures were incubated with
      Hcy (10-100 micromol/l) +/- IL-1beta, and IL-6 and IL-8 concentrations were
      evaluated in the supernatants (ELISA) together with the activation of nuclear
      factor-kB (NF-kB) (immunocytochemistry). RESULTS: Hcy was present in synovial
      fluids, with a mean concentration significantly higher in RA patients than in
      controls (9.0 +/- 1.1 vs 5.9 +/- 1.2 micromol/l). Hcy enhanced IL-6 and IL-8
      production in RA synoviocytes only (up to 35%). Moreover, Hcy produced a clear
      cut activation of NF-kB in rheumatoid cells only. CONCLUSION: Hcy enhances IL-1
      dependent cytokine production by rheumatoid synoviocytes at a concentration
      measurable in RA joints in vivo. Thus, in RA patients, Hcy may not only represent
      an important risk factor for the progression of cardiovascular diseases, but it
      may also contribute to the joint damage.

PMID- 16956429
TI  - Clinical significance of serum matrix metalloproteinase-13 levels in patients
      with localized scleroderma.
AB  - OBJECTIVES: To investigate the clinical significance of serum matrix
      metalloproteinase-13 (MMP-13) levels in patients with localized scleroderma
      (LSc). METHODS: Serum MMP-13 levels were determined by using a peptide substrate
      cleavage assay in 10 patients with generalized morphea, 10 with linear
      scleroderma, 10 with morphea, and 10 normal controls. RESULTS: The serum MMP-13
      levels in patients with LSc were lower than those in normal controls, but there
      was no significant difference (64.9 +/- 19.9 versus 73.2 +/- 11.5, p = 0.058).
      Serum MMP-13 levels in patients with generalized morphea were significantly lower
      than those in normal controls (54.0 +/- 18.7 versus 73.2 +/- 11.5 ng/ml; p <
      0.01). Serum levels of MMP-13 were comparable among normal controls, the patients
      with linear scleroderma, and those with morphea. The prevalence of muscle
      involvement was significantly greater in the LSc patients with decreased MMP-13
      levels compared with those with normal MMP-13 levels (50% versus 8%, p < 0.05).
      Serum MMP-13 levels were significantly inversely correlated with the number of
      linear lesions (r = 0.366, p < 0.05) and the number of involved body areas (r =
      0.552, p < 0.005) in patients with LSc, while there was no significant
      correlation between serum MMP-13 levels and the number of plaque lesions.
      Furthermore, there was significant inverse correlation between serum MMP-13
      levels and the number of involved body areas in patients with generalized morphea
      (r = 0.631, p < 0.05). CONCLUSION: The serum MMP-13 levels may reflect the
      disease severity in patients with LSc, especially generalized morphea, the
      severest form of this disorder.

PMID- 16956430
TI  - IB-MECA, an A3 adenosine receptor agonist prevents bone resorption in rats with
      adjuvant induced arthritis.
AB  - OBJECTIVES: The anti-inflammatory effect of adenosine is partially mediated via
      the A3 adenosine receptor (A3AR), a Gi protein associated cell surface receptor.
      The highly selective A3AR agonist, IB-MECA was earlier shown to prevent the
      clinical and pathological manifestations of arthritis in experimental animal
      models of collagen and adjuvant induced arthritis (AIA). In this study we tested
      the effect of IB-MECA on the prevention of bone resorption in AIA rats and looked
      at the molecular mechanism of action. METHODS: Rats with AIA were treated orally
      twice daily with IB-MECA starting upon onset of disease and the clinical score
      was evaluated every other day. At study termination the foot, knee and hip region
      of both vehicle and IB-MECA treated animals were subjected to histomorphometric
      analysis. Western blot analysis was carried out on paw protein extracts. RESULTS:
      IB-MECA ameliorated the clinical manifestations of the disease and reduced pannus
      and fibrosis formation, attenuated cartilage and bone destruction and decreased
      the number of osteoclasts. In cell protein extracts derived from paw of AIA rats,
      A3AR was highly expressed in comparison to naive animals. In paw extracts derived
      from IB-MECA treated AIA rats, down-regulation of the A3AR protein expression
      level was noted. PI3K, PKB/Akt, IKK, NF-kappaB, TNF-alpha and RANKL were down
      regulated whereas caspase 3 was up-regulated. CONCLUSION: IB-MECA, a small highly
      bioavailable molecule, induces modulation of proteins which control survival and
      apoptosis resulting in the amelioration of the inflammatory process and the
      preservation of bone mass in AIA rats.

PMID- 16956431
TI  - The level of anti-topoisomerase I antibodies highly correlates with
      metacarpophalangeal and proximal interphalangeal joints flexion contractures in
      patients with systemic sclerosis.
AB  - BACKGROUND: It is found that an antibody directed against DNA topoisomerase I
      (anti-topo I abs) is detected almost exclusively in systemic sclerosis (SSc).
      These antibodies are predictors of pulmonary fibrosis and peripheral vascular
      disease. OBJECTIVE: Metacarpophalangeal (MCP) and proximal interphalangeal (PIP)
      joints flexion contractures are assessed as markers of active SSc. The aim of
      this study was to find out is there any relationship between anti-topo I abs and
      MCP and PIP joints flexion contractures. METHODS: Twenty-eight patients with
      active disease who fulfilled the American College of Rheumatology criteria for
      SSc were included in this study. Twenty eight healthy control subjects were also
      investigated. Clinical and radiological assessments of the hands were carried
      out. The flexion ranges in the 8 finger joints by goniometric measurement were
      obtained. Anti-topo I abs with an enzyme linked immunosorbent assay (ELISA) were
      measured. RESULTS: MCP and PIP joints flexion contractures and the levels of anti
      topo I abs were significantly higher in patients with systemic sclerosis than in
      healthy control. The anti-topo I abs were found in 16 of 28 patients with
      systemic sclerosis. Sixteen of 28 patients with active disease had MPC and
      proximal PIP joints flexion contractures. In 16 SSc patients with anti-topo I
      abs, 13 had metacarpophalangeal and proximal interphalangeal joints flexion
      contractures. In only 3 patients of 16 with the flexion contractures the levels
      of anti-topo I abs were negative. The patients with MPC and PIP joints flexion
      contractures had higher mean value of anti-topo I abs titers (53.718 +/-50.977 vs
      8.127 +/- 8.915, P < 0.0001) than did those with no contractures. Furthermore,
      the titers of anti-topoisomerase I antibody positively correlated with the
      flexion contractures (r = 0.4252, P = 0.0241). Radiologically, joint space
      narrowing and flexion contractures of the fingers were seen significantly more
      frequently in the SSc patients with anti-topo I abs (P < 0.05). CONCLUSION: Serum
      level of anti-topoisomerase I antibodies is in direct relationship with MPC and
      PIP joints flexion contractures.

PMID- 16956432
TI  - Recommendations for the use of biologic (TNF-alpha blocking) agents in the
      treatment of rheumatoid arthritis in Italy.
AB  - The present report is devoted to drawing up and disseminating specific
      recommendations for the use of anti-TNF-alpha therapies in patients with
      rheumatoid arthritis (RA) in Italy. The document reports and discusses the
      published literature concerning the criteria for inclusion, assessment of
      response and for withdrawal of treatment with TNF blocking agents in RA. Several
      specific points concerning more sensitive warnings are discussed: tuberculosis,
      hepatitis, lymphoma, and cardiovascular risk and induction of autoimmunity. The
      recommendations are summarized in an 8-point table approved by the executive
      committee of the Italian Society for Rheumatology.

PMID- 16956433
TI  - Unexplained musculoskeletal pain in people of South Asian ethnic group referred
      to a rheumatology clinic - relationship to biochemical osteomalacia, persistence
      over time and response to treatment with calcium and vitamin D.
AB  - BACKGROUND: Hypovitaminosis D continues to be a problem for South Asian people
      living in the UK. This study investigates the association between widespread
      unexplained pain and biochemical osteomalacia in this group of people. METHODS:
      All South Asian patients attending with unexplained widespread pain (CWP) over a
      two-year period had biochemical tests for osteomalacia: calcium, phosphate,
      alkaline phosphatase, vitamin D (25OHD), and parathyroid hormone (PtH). For
      comparison, a control group consisted of patients in whom a specific rheumatic
      diagnosis (SRD) had been made. A follow up questionnaire was sent enquiring about
      pain, disability and dietary habits. A small proportion of the responders
      attended for a further set of biochemical tests for osteomalacia. RESULTS: The
      majority of patients in both groups had a raised PtH (124/220, 57%) and a low
      25OHD (117/160, 73%). Where data on both PtH and 25OHD were available, 47%
      (64/137) had a combination of reduced 25OHD and raised PtH. Few of these patients
      had abnormal calcium, phosphate or alkaline phosphates. From the postal
      questionnaire the prevalence of disability and continuing pain was high in both
      groups, with the majority of respondents complaining of difficulty with
      activities and nearly half needing help. Pain was widespread, the same or worse
      and graded above 7/10 for 69% and 78% of respondents in the CWP and SRD groups
      respectively. Overall, sixty one percent of respondents thought their gait
      pattern had changed in the last year. No significant differences were seen
      between respondents based on diagnosis (CWP or SRD), initial or subsequent PtH
      levels, or current calcium and vitamin D consumption. At the time of the second
      blood test, 52% of those with an elevated PtH on the first test now had a normal
      PtH value but 31% of those with a normal PtH first time had an elevated PtH.
      CONCLUSION: This observational study conducted in a rheumatology clinic in the
      north of England has shown high levels of biochemical osteomalacia in people of
      South Asian origin and high levels of persistent pain and disability, unrelated
      to diagnosis, biochemical status or treatment with calcium and vitamin D.

PMID- 16956434
TI  - Bone turnover and hormonal perturbations in patients with fibromyalgia.
AB  - OBJECTIVE: Studies of bone turnover in fibromyalgia (FM) have, to date, shown
      conflicting results. Although most patients with FM are women, only a few
      investigations have paid attention to the changes of sex hormones in FM.
      Moreover, FM is often viewed as a stress related disorder, and abnormalities of
      the hypothalamic-pituitary-adrenal (HPA) axis have been found in FM. The aim of
      the study was to assess bone turnover using serum osteocalcin and CTx in patients
      with FM and study correlation between bone turnover parameters and parathormon
      and hormones of the HPA axis. METHODS: A total of 81 subjects participated in
      this study: 41 healthy volunteers and 40 patients with FM. Serum osteocalcin,
      crosslaps (C-telopeptide: CTx), parathyroid hormone (PTH), testosterone,
      estrogen, prolactin, FSH, and LH were measured. The mean age of the study
      population was 49.5 (7.6) years (32-69) and the mean disease duration was 8.1
      (12.0) years (4.5-30.7). RESULTS: No difference between patients and controls
      were observed in serum calcium, phosphorus, creatinine, albumin, osteocalcin,
      testosterone, and urinary calcium. Patients had lower serum levels of CTx,
      estrogen, PTH and prolactin than controls and higher serum levels of LH and FSH
      with a significant statistical difference. No significant statistical correlation
      was observed between intensity of pain and fatigue and bone turnover parameters
      and PTH or hormones of the HPA axis. CONCLUSION: Our study showed that patients
      with FM had low bone resorption and normal bone formation compared to a control
      group. This was not related to several hormonal perturbations observed in these
      patients and may reflect functional impairment as suggested in previous studies.

PMID- 16956435
TI  - Etrurians vs Greeks: May ACE I/D polymorphism still be considered as a marker of
      susceptibility to SSc?
AB  - OBJECTIVE: SSc is characterized by immune dysfunction and microvascular
      involvement. A different genetic background may determine a different polymorphic
      allele frequency between different populations, and data from literature reported
      conflicting results about the role of genetic components in predisposing to the
      disease. We carried out this study in order to compare the ACE I/D polymorphism
      genotype distribution and alleles frequency in two different populations from the
      Mediterranean area. METHODS: Forty-eight Italian and 41 Greek SSc patients
      compared with 112 Italian and 93 Greek controls, have been studied. The ACE I/D
      polymorphism has been analysed. RESULTS: The genotype distribution and allele
      frequency were in Hardy-Weinberg equilibrium for Italian and Greek SSc patients
      and controls. Among the Italian patients a significantly higher ACE D allele
      frequency than in the controls was found, whereas among the Greeks a higher
      prevalence was observed in the healthy subjects. A significant difference in ACE
      D allele frequency between Italian and Greek controls was observed (p = 0.04).
      ACE D allele was associated to the predisposition to SSc in Italians, but not in
      Greeks. CONCLUSION: We confirm that Italian SSc patients have a higher ACE D
      allele frequency that is not present in the Greek patients. Thus, the two
      populations living in different Mediterranean areas and resulting from the
      Mediterranean civilization, do not show the same ACE-gene related allele
      frequencies. Other populations of the Mediterranean area must be investigated by
      using unlinked genetic markers to verify the homogeneity of the genetic
      background, and to test for a "true" difference in their ethnic origin.

PMID- 16956436
TI  - Etanercept in the treatment of arthritis in a patient with familial Mediterranean
      fever.
AB  - Familial Mediterranean fever (FMF) patients may present with different joint
      complaints, one being the 'protracted attack' that lasts for weeks. We present a
      15 year-old boy with polyarthritis (right wrist, knee, shoulder, and both ankles)
      while on colchicine treatment for FMF. His polyarthritis was resistant to
      treatment with prednisolone and methotrexate, and etanercept was instituted (0.8
      mg/kg/week). He responded dramatically to etanercept and remained in full
      remission, although the drug was stopped at 4 months due to social and financial
      causes. We suggest that anti-TNF drugs may be an alternative for resistant
      attacks. However the timing and dosage, as well as efficacy, need to be further
      studied.

PMID- 16956437
TI  - Hematologic manifestations of primary Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) is a chronic autoimmune disorder, primarily characterized
      by the mononuclear cell infiltration of exocrine glands exiting in parenchymal
      damage and secretory impairment. The spectrum of the disease extends from an
      autoimmune exocrinopathy to a systemic process with extraglandular
      manifestations. SS is defined as primary (pSS) when isolated, or secondary when
      associated with another autoimmune disease. Patients with pSS may present
      hematologic abnormalities, such as anemia, hemocytopenias, monoclonal
      gammopathies and lymphoprolipherative disorders, predominantly non-Hodgkin's
      lymphoma of B-cell origin. The increased prevalence of B-cell malignancies
      suggests that SS may be a boundary disease between autoimmunity and
      lymphoproliferation. In this paper, the hematologic manifestations of pSS are
      reviewed.

PMID- 16956438
TI  - The diagnostic value of anti-cyclic citrullinated peptide (CCP) antibodies in
      children with Juvenile Idiopathic Arthritis.
AB  - BACKGROUND: Antibodies against cyclic citrullinated peptide (anti-CCP) are
      considered to be specific for rheumatoid arthritis (RA). OBJECTIVE: To assess the
      clinical significance of anti-CCP antibodies in a cohort of patients with
      juvenile idiopathic arthritis (JIA) and if they can be used to identify patients
      with an unfavourable course of disease. METHODS: 68 serum samples were
      investigated. 45 patients were diagnosed with JIA (15 male and 30 female) aged
      1.9-17.3 years (median 12.9 mean 11,0). 5 patients had polyarticular (RF
      negative), 2 polyarticular (RF positive), 25 oligoarticular JIA, 6 enthesitis
      related arthritis, 2 psoriatric arthritis, 3 patients had systemic disease and 2
      unclassified arthritis. 23 samples were taken from patients with non-inflammatory
      cardiac diseases undergoing interventional cardiac therapy. Enzyme-linked
      immunosorbent assay (ELISA; Euroimmun, Lubeck, Germany) was used for the
      detection and quantification of anti-CCP antibodies in patients with JIA.
      RESULTS: Overall, anti-CCP antibodies were found in 2.9% (2/68) of all samples
      and in 4.4 % (2/45) patients with JIA. CONCLUSION: Anti-CCP antibodies are
      associated with RF positive polyarticular course of JIA. Anti-CCP antibodies are
      not relevant for other subgroups of JIA. Therefore anti-CCP Abs in patients with
      JIA should not be investigated routinely.

PMID- 16956439
TI  - Citrullinated filaggrin is decreased in oral keratinocytes in rheumatoid
      arthritis.

PMID- 16956440
TI  - Efficacy of infliximab in long-lasting refractory Kawasaki disease.

PMID- 16956442
TI  - Fever with rash following zolendronic acid administration.

PMID- 16956441
TI  - Analyses of ADAMTS13 activity and its inhibitor in patients with thrombotic
      thrombocytopenic purpura secondary to connective tissue diseases: Observations in
      a single hospital.

PMID- 16956443
TI  - What is the government doing to cardiology?

PMID- 16956444
TI  - Complications associated with implantable cardioverter defibrillator replacements
      associated with recalls.

PMID- 16956445
TI  - Sudden cardiac death in athletes.
AB  - The impact of sudden cardiac death (SCD) in athletes has been highlighted by
      increasing media coverage, as well as medical and lay awareness of the entities
      associated with SCD. Common etiologies include cardiac abnormalities such as
      hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular
      dysplasia/cardiomyopathy (ARVD), and coronary artery anomalies, each with varying
      geographic incidence. New recommendations regarding noninvasive preparticipation
      screening have emerged in Europe, where the Italian experience of mandatory
      annual screening of athletes has been the forerunner in efforts to identify
      individuals at risk. Ongoing clinical efforts are underway to help define the
      role of implantable cardioverter defibrillators as a preventive measure in
      appropriate candidates with HCM or ARVD, as well as methods to limit the
      potential for SCD as a result of chest blows sustained in sports and other
      recreational activities by means of chest protectors and special sporting
      equipment for young athletes.

PMID- 16956446
TI  - Medical management of atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained tachyarrhythmia encountered
      in clinical practice. The management of AF remains associated with many
      challenges that make its treatment a vexing problem. However, in recent years
      extraordinary progress has been made in the understanding and management of AF.
      In general, antiarrhythmic drugs for rhythm control have been disappointing. We
      have a better understanding of pharmacologic cardioversion and this has led to
      newer strategies, such as intermittent therapy. Several studies have been
      completed comparing pharmacologic rhythm control with pharmacologic heart rate
      control. There is also an emerging body of evidence concerning the value of
      adjunctive drug use for rhythm control using drugs that would not usually be
      considered to be antiarrhythmic. Finally, antithrombotic therapy is an
      increasingly important part of the medical management of AF. This article
      summarizes the results of many of the recent publications and their clinical
      implications concerning management of this common rhythm disorder.

PMID- 16956447
TI  - New indications for implantable defibrillator therapy.
AB  - Implantable cardioverter defibrillator (ICD) therapy has been extensively
      evaluated in patients at high risk of sudden cardiac death. Most recently, the
      Sudden Cardiac Death in Heart Failure Trial found that patients with moderate
      symptoms of congestive heart failure, whether due to an ischemic or a nonischemic
      cause, have reduced mortality compared with patients treated only with
      conventional medical therapy for heart failure. The results of this trial confirm
      those of earlier trials finding a benefit of ICD therapy in patients with
      coronary artery disease and reduced left ventricular systolic function, and
      extend the indications for ICD therapy to those without coronary artery disease.

PMID- 16956448
TI  - Cardiac resynchronization therapy: role of patient selection.
AB  - Cardiac resynchronization therapy (CRT) is a well-accepted and effective therapy
      for treating patients with a wide QRS complex, significant left ventricular
      systolic dysfunction, and symptoms of advanced heart failure. However,
      approximately 25% to 30% of patients fail to respond to this therapy. Most large
      studies have used electrical dyssynchrony (wide QRS) as a main entrance
      criterion. Emerging data suggest that mechanical dyssynchrony may be a more
      important factor in selecting appropriate candidates for CRT. New
      echocardiographic (ECHO) imaging modalities such as tissue Doppler imaging, three
      dimensional ECHO, and speckle tracking ECHO are able to quantify left ventricular
      mechanical dyssynchrony. These techniques are currently being used to assist in
      the selection of patients for CRT. Recently published and ongoing studies are
      addressing the use of CRT in patients who do not meet the standard criteria, such
      as patients with atrial fibrillation, mild to moderate heart failure, narrow QRS
      complex, and acute myocardial infarction.

PMID- 16956449
TI  - Ablation of atrial fibrillation.
AB  - Fueled by dissatisfaction with pharmacologic strategies to treat atrial
      fibrillation (AF), the results of basic and clinical investigation into the
      understanding of AF initiation and maintenance mechanisms, and the explosive
      development in catheter-based technologies, AF ablation has matured from a purely
      investigational technique to a preferred, safe, and effective approach for curing
      AF, particularly with the circumferential approach. Future insights and
      developments will help us refine our treatment strategies in patients with
      permanent AF, making chronic AF ablation safer, faster, and more effective. As
      the prevalence of AF in the general population continues to increase, the purpose
      of optimizing our strategy becomes evermore important and more pressing.

PMID- 16956450
TI  - Amiodarone: a multifaceted antiarrhythmic drug.
AB  - Synthesized as an antianginal compound 40 years ago, amiodarone has emerged as a
      uniquely effective antiarrhythmic compound in recent years. It has numerous
      properties, the most prominent being the ability to lengthen repolarization in
      the atria and ventricles associated with bradycardia without the significant
      potential for torsades de pointes. Amiodarone effectively controls a wide
      spectrum of atrial and ventricular antiarrhythmic disorders, but its limiting
      side effects, such as thyroid dysfunction, pulmonary fibrosis, and dermatologic
      changes, may limit its long-term use in some patients. What aspects of the
      multiplicity of the properties of amiodarone are relevant to its unusual efficacy
      is not known. Deiodination and other structural changes in the amiodarone
      molecule have has led to a the loss of thyroid and pulmonary effects in the
      resulting derivative, dronedarone, which is in advanced clinical development.

PMID- 16956451
TI  - Use of beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin
      receptor blockers to prevent atrial fibrillation.
AB  - Atrial fibrillation, the most common cardiac arrhythmia in clinical practice,
      causes significant burden to patients and health care systems worldwide.
      Attention is being paid to prevention of atrial fibrillation using drugs that
      retard or prevent atrial fibrosis and arrhythmogenic remodeling, which lead to
      this arrhythmia. Agents that work through the renin-angiotensin-receptor system,
      the angiotensin-converting enzyme inhibitors and angiotensin receptor blockers,
      are showing promise in animal and human studies.

PMID- 16956452
TI  - Is there a role for antiarrhythmic drugs in patients with implantable
      defibrillators?
AB  - With remarkable advancement in technology and clinical research, implantable
      cardioverter defibrillators (ICDs) have replaced antiarrhythmic drugs as the
      preferred modality for both primary and secondary prevention of arrhythmic
      deaths. However, concomitant use of antiarrhythmics in patients with ICDs remains
      common, often for prevention or reduction of appropriate and inappropriate shocks
      caused by ventricular and supraventricular arrhythmias, respectively. The role of
      empiric antiarrhythmic therapy in this patient population remains less clearly
      defined, with conflicting information from various small randomized trials. Use
      of antiarrhythmic drugs in the ICD patient population not only can cause
      potentially serious side effects but can also interact or interfere with the ICD
      device function. In addition, the effect on survival in patients with ICDs is not
      well characterized. Given the many potential side effects, drug-device
      interactions, unclear survival effect, and lack of convincing clinical data
      supporting its use, empiric antiarrhythmic therapy in the ICD patient population
      cannot be recommended at this time.

PMID- 16956453
TI  - Atrial fibrillation: choosing an antiarrhythmic drug.
AB  - Atrial fibrillation is the most common arrhythmia encountered in clinical
      practice. The associated hemodynamic changes can lead to symptoms of
      palpitations, fatigue, light-headedness, or dyspnea. Extensive research in the
      use of antiarrhythmic drugs has been performed both to facilitate the conversion
      of atrial fibrillation to sinus rhythm and to maintain normal sinus rhythm. The
      relative merits of a rhythm control versus rate control strategy are briefly
      discussed. Efficacy of the available agents for pharmacologic cardioversion is
      reviewed in detail. Important drugs for maintenance of sinus rhythm include
      amiodarone, flecainide, propafenone, sotalol, and dofetilide. Selection of the
      appropriate antiarrhythmic drug must be individualized to the clinical situation,
      with Class IC drugs being first-line agents in the absence of structural heart
      disease. Regardless of agent selected, appropriate monitoring for development of
      adverse effects is of utmost importance.

PMID- 16956454
TI  - p-Phenylenediamine.

PMID- 16956455
TI  - Allergic contact dermatitis from mercapto compounds.
AB  - Despite being well-known allergens, mercaptobenzothiazole and its derivatives
      continue to be widely used in natural and synthetic rubber, in the mining
      industry, and in a variety of nonrubber products. The purpose of this article is
      to review the epidemiology and the clinical characteristics of allergic contact
      dermatitis from mercapto compounds.

PMID- 16956456
TI  - Allergenicity and cross-reactivity of coconut oil derivatives: A double-blind
      randomized controlled pilot study.
AB  - BACKGROUND: Counseling of patients with cocamidopropyl betaine (CAPB) allergy is
      difficult because the cross-reactivity of CAPB with other coconut-derived
      surfactants, coconut oil, and coconut fatty acids is largely unknown. OBJECTIVE:
      To provide pilot data regarding the cross-reactivity and allergenicity of
      surfactants derived from coconut oil. METHODS: A randomized double-blind
      controlled pilot study of 10 control patients and 12 patients previously found to
      be allergic to CAPB. Eleven coconut-derived surfactants, as well as coconut oil
      and lauric acid, were applied in random order according to standardized patch
      test procedures with readings at 48 and 92 hours. The primary outcome measure was
      the frequency of positive patch-test reactions to each allergen. RESULTS: Only 3
      of the 12 patients with previous reactions to CAPB reacted on retesting, and all
      of these reactions were doubtful. Fifty-nine percent of the study patients had
      reactions to triethanolamine polyethylene glycol-3 (TEA-PEG-3) cocamide sulfate
      as compared to none of the controls (p = .005). CONCLUSIONS: Reactions to CAPB
      were only 25% reproducible. These results substantiate previous experience that
      doubtful and mild reactions to CAPB may represent irritant reactions as opposed
      to true allergic reactions. TEA-PEG-3 cocamide sulfate was the only agent that
      had a statistically significant higher rate of reactions in the study group as
      compared to the control group.

PMID- 16956457
TI  - The utility of the TRUE test in a private practice setting.
AB  - BACKGROUND: Studies suggest that the Thin-Layer Rapid-Use Epicutaneous Test (TRUE
      Test) may be inadequate to completely diagnose a significant number of patients
      with allergic contact dermatitis (ACD). OBJECTIVE: To study the usefulness of the
      TRUE Test as a triage tool in a private practice setting. METHODS: A
      retrospective chart review of patients who were patch-tested with the TRUE Test
      between July 1, 2000, and June 30, 2004, in four private dermatology practices
      was conducted. RESULTS: Of the 183 patients evaluated, 50.8% had at least one
      positive reaction, 31.7% had a diagnosis of ACD, and 24.0% were suspected to have
      ACD from other allergens. Of the patients with positive reactions, 62.4% were
      determined to have reactions that were of present relevance. CONCLUSIONS: The
      TRUE Test allows patients with dermatitis to be triaged systematically in a
      private practice setting. It is important to supplement patch testing with the
      patients' personal products, especially in cases of facial or periorbital
      dermatitis, and to be aware of potential false negatives, particularly with
      fragrance and rubber additives.

PMID- 16956458
TI  - Allergic contact dermatitis from EMLA cream in a hemodialyzed patient.
AB  - The eutectic mixture EMLA cream has many medical uses, including pain relief for
      hemodialyzed patients prior to cannulation. Cutaneous side effects associated
      with its application have rarely been reported. A patient on hemodialysis
      developed an itchy eruption over his brachial arteriovenous fistula, where he was
      applying EMLA cream three times per week, prior to puncture for hemodialysis.
      Patch testing elicited a positive reaction to several allergens, including EMLA
      cream "as is" and prilocaine. The lesions resolved after topical treatment with
      corticosteroids.

PMID- 16956459
TI  - Allergic contact stomatitis.

PMID- 16956460
TI  - Lidocaine sensitivity in a patient with multiple skin cancers.

PMID- 16956461
TI  - The relationship of vehicle and concentration for imidazolidinylurea, with
      attention to formaldehyde allergy status.

PMID- 16956462
TI  - Cutaneous reactions to transdermal therapeutic systems.
AB  - Transdermal therapeutic systems have been increasingly used in the past two
      decades. However, cutaneous side effects are fairly common and may result in poor
      patient compliance. This review article summarizes the spectrum of reactions due
      to transdermal therapeutic systems and provides a current list of known
      allergens.

PMID- 16956463
TI  - Prevalence and morphology of hand eczema in patients with atopic dermatitis.
AB  - BACKGROUND: Patients with hand eczema frequently have a history of atopic
      dermatitis or atopy. No specific morphologic pattern of hand eczema helps
      distinguish atopic hand eczema from other etiologies. There are few studies of
      hand eczema prevalence and morphology in a well-defined population of patients
      with atopic dermatitis. METHODS: We evaluated 777 consecutive patients with
      atopic dermatitis (diagnosed by standard criteria) for hand involvement. An
      additional 100 patients had further evaluations, including evaluation of the
      historical and morphologic characteristics of their hand eczema. RESULTS: The
      prevalence of hand involvement in patients with active atopic dermatitis was
      58.9% (458 of 777 patients). Nail dystrophy was present in 16% (124 of 777) of
      patients. There was a significant trend toward an increasing prevalence of hand
      involvement with increasing age. Hand eczema tended to involve primarily the
      dorsal hand surfaces and the volar wrist. CONCLUSIONS: The hands are frequently
      involved in patients with active atopic dermatitis and present unique physical,
      social, and therapeutic challenges for patients. During the evaluation of
      patients presenting with hand eczema, the involvement of dorsal hand surfaces and
      the volar wrist may suggest atopic dermatitis as a contributing etiologic factor.

PMID- 16956464
TI  - Radiation therapy for chronic vesicular hand dermatitis.
AB  - BACKGROUND: Chronic vesicular hand dermatitis is a chronic disease that can be
      debilitating for patients, and many treatment options do not provide lasting
      remission. OBJECTIVE: We attempted to determine the efficacy of megavoltage
      irradiation in the treatment of this disease. METHODS: Between July 2001 and
      March 2005, 9 patients with severe chronic vesicular hand dermatitis had
      megavoltage radiation therapy to their sites of disease. Eight pairs of hands and
      seven pairs of feet were irradiated (15 total sites). RESULTS: All patients had
      an improvement in their disease during the course of radiation therapy. Patients
      were followed after radiation therapy for a median follow-up time of 20.2 months
      (range, 1 to 45 months). The disease completely resolved in 7 of the 15 (47%)
      sites irradiated. There was a decrease in the severity or frequency of flare-ups
      at the other 8 sites (53%). CONCLUSION: Megavoltage radiation therapy may be
      effective in the treatment of chronic vesicular hand dermatitis and may provide
      durable remissions in some patients.

PMID- 16956465
TI  - Optimizing reproducibility for clinical studies involving patch testing and
      application of topical preparations.
AB  - BACKGROUND: The reproducibility and consistency of patch-test techniques can be
      problematic, making controlled clinical trials of patch testing difficult.
      OBJECTIVE: To measure the accuracy and reproducibility of applying controlled
      quantities of petrolatum onto Finn Chambers. METHODS: Four dermatology nurses
      applied a total of 240 samples of white petrolatum, using three syringe sizes and
      types. Three different amounts of white petrolatum (0.02 mL, 0.05 mL, and the
      "usual" amount) were expressed onto previously weighed Finn Chambers, using three
      different syringe sizes (5 mL, 1 mL, and 0.5 mL), five times each on two separate
      days. RESULTS: The average weights of 0.05 mL of petrolatum expressed with each
      type of syringe (5 mL: 0.04252 g; 1 mL: 0.04084 g; and 0.5 mL: 0.04139 g) were
      not significantly different from each other in pairwise comparisons (p > .36) or
      from the "gold standard" expected value (0.04138 g, p > .72). The average weights
      of 0.02 mL of petrolatum expressed with two types of syringes (5 mL: 0.02138 g;
      0.5 mL: 0.01778 g) were significantly different from each other (p = .0012), but
      neither differed significantly from the expected value (0.01655 g, p > .08). The
      variance due to the effect modifications of nurse, day, and interaction of nurse
      and day was statistically significant for measurements made with the 5 mL syringe
      but not for measurements made with the 1 mL or 0.5 mL syringe. CONCLUSION: The
      average amounts of petrolatum extruded from smaller syringes (0.5 mL and 1 mL)
      were less variable and more reproducible than those extruded from a 5 mL syringe.

PMID- 16956466
TI  - Allergic contact dermatitis from corticosteroids: reproducibility of patch
      testing and correlation with intradermal testing.
AB  - BACKGROUND: Corticosteroid contact allergy is not uncommon. The diagnosis can be
      made with either patch testing or intradermal (ID) testing. In view of a few
      problems that have been encountered with patch testing, patch testing is
      considered inferior to ID testing. The reported reproducibility of positive patch
      test results in the literature ranges from 47 to 98%. OBJECTIVES: This study was
      conducted to (1) determine the reproducibility of patch testing with topical
      steroid preparations and their clinical relevance, (2) correlate positive results
      with ID testing, (3) address the issue of cross-reactivity between different
      steroid groups, and (4) identify the percentage of positive reactions to
      preservatives and vehicles used in commercial topical steroids. METHODS: A total
      of 19 patients with positive patch-test reactions to steroids from 1995 to 2004
      were identified. Atopic patients and patients with type I hypersensitivity were
      excluded. The patients were patch-tested with a steroid series, select commercial
      steroid products, and vehicles and preservatives used in these preparations. The
      same patients were subjected to ID testing with select steroids. Readings were
      done on days 2, 5, and 7. ID testing was also performed on 9 control patients.
      RESULTS: Tixocortol-21-pivalate is the most common steroid allergen (68%). The
      reproducibility of patch testing with topical steroid preparations ranged from 66
      to 100%. Reactions to both ID testing and patch testing occurred in 16 patients
      (89%); 1 patient reacted to patch testing and 1 other reacted to ID testing.
      Formaldehyde and formaldehyde releasers accounted for the majority of reactions
      in the vehicles and preservatives group. CONCLUSION: Patch testing is sufficient
      in diagnosing allergic contact dermatitis from topical steroids. Testing with
      commercial products is not a good screen for steroid allergy. The most common
      cross-reactions were between group A (hydrocortisone-type) corticosteroids and
      group D2 corticosteroids (composed of labile esters, with a long-chain ester at
      C17 and possibly C21).

PMID- 16956467
TI  - Cutaneous reactions to injectable corticosteroids.
AB  - Corticosteroids are used to treat a variety of medical conditions. While topical
      preparations are known to commonly cause allergic contact dermatits, systemic use
      of these drugs rarely causes cutaneous reactions. (This paper presents) Two cases
      of (systemic) injectable corticosteroid use resulting in delayed hypersensitivity
      reactions are presented.

PMID- 16956468
TI  - Cross-reactions to desoximetasone and mometasone furoate in a patient with
      multiple topical corticosteroid allergies.
AB  - A 60-year-old man developed a bullous contact dermatitis after topical
      corticosteroid treatment of dermatitis on his lower leg. Subsequent patch testing
      showed cross-reactions to numerous group B and group D corticosteroids as well as
      cross-reactions to group C desoximetasone and group D1 mometasone furoate. His
      patch-test result was negative for the group A corticosteroids hydrocortisone and
      tixocortol pivalate. We discuss the uncommon finding of cross-reactions to
      desoximetasone and mometasone furoate.

PMID- 16956469
TI  - Allergic contact dermatitis from octisalate and cis-3-hexenyl salicylate.
AB  - A 62-year-old woman developed allergic contact dermatitis from sunscreens
      containing octisalate (octyl salicylate, 2-ethylhexyl salicylate) and from a
      fragrance containing cis-3-hexenyl salicylate. Results of patch testing and
      provocative use testing confirmed that she was allergic to octisalate.
      Provocative use testing indicated that she was also allergic to cis-3-hexenyl
      salicylate.

PMID- 16956470
TI  - Allergic contact dermatitis to chloroxylenol.
AB  - Chloroxylenol, also known as p-chloro-m-xylenol (PCMX), is a compound that has
      been used as a preservative in cosmetics and as an active agent in antimicrobial
      soaps. We present two patients with allergic contact dermatitis from PCMX,
      confirmed by positive (+++) patch-test reactions at 48 and 72 hours,
      identification of PCMX in a soap and in a hand cream used by the patients, and
      improvement following withdrawal of the incriminating products. The mechanism of
      action, structure, antimicrobial activity, and dangers of PCMX are reviewed.

PMID- 16956471
TI  - Bullous fixed drug eruption induced by paracetamol: report of a case.

PMID- 16956472
TI  - Excited skin syndrome associated with patch-test application technique.

PMID- 16956473
TI  - Endovascular therapy as the primary approach for limb salvage in patients with
      critical limb ischemia: experience with 443 infrapopliteal procedures.
AB  - Endovascular strategies for the treatment of critical infrageniculate peripheral
      arterial occlusive disease exist and are becoming the primary methodology for
      such lesions at many centers. Although technically feasible for experienced
      operators, the evidence to support this strategy for below the knee (BTK)
      interventions is still evolving. We studied the 6-month and 1-year outcomes of
      percutaneous transluminal angioplasty (PTA) alone, PTA with stenting, and excimer
      laser recanalization for BTK lesions in patients with critical limb ischemia.
      Between September 2002 and June 2005, 443 patients (355 Rutherford category 4, 82
      category 5, 6 category 6) underwent intervention for 681 BTK lesions. Follow-up
      was performed at 6-month intervals after index intervention: limb salvage data
      were recorded and duplex ultrasonography was performed to measure the patency of
      treated areas. The primary patency and limb salvage rates of the entire
      population were 85.2% and 97.0% and 74.2% and 96.6% at 6 months and 1 year,
      respectively. Stratified for the treatment strategy (PTA alone in 79, PTA with
      stenting in 300 patients, and excimer laser in 64), 1-year primary patency rates
      were 68.6%, 75.5%, and 75.4%, whereas the limb salvage rates were 96.7%, 98.6%,
      and 87.9% for each modality, respectively. Endovascular intervention will become
      the primary treatment for BTK lesions in patients with critical limb ischemia,
      with 1-year primary patency and limb salvage rates that compare favorably with
      published surgical data. Prospective, randomized, multicenter trials will be
      needed to further establish the role of endovascular intervention in this
      challenging patient group.

PMID- 16956474
TI  - Prospective evaluation of factors associated with early failure of arteriovenous
      fistulae in hemodialysis patients.
AB  - Recent guidelines have recommended performing native arteriovenous fistulae (AVF)
      in hemodialysis patients rather than synthetic grafts whenever possible. However,
      early failure of AVF may reach up to 50%. The purpose of this study was to assess
      the factors associated with early failure of such procedures in hemodialysis
      patients. A prospective study was performed on all patients with end-stage renal
      disease who had an AVF between June 2003 and March 2005. Data including patient
      characteristics and the type of AVF were recorded. The internal diameter of the
      vein and artery and intraoperative blood flow were measured. Patients were
      followed up for 3 months. One hundred twenty-six AVF were included in this study.
      Early failure was in 14 (9%) patients. The internal diameter of the vein and
      artery and intraoperative blood flow were significantly lower in the failure
      group than in the patent group. The failure rate was not significantly related to
      other parameters. Our data showed that intraoperative blood flow is a reliable
      parameter that determines the early failure of an AVF. Careful selection of the
      vein and the artery may reduce the rate of failure.

PMID- 16956476
TI  - Comparison of the results of percutaneous transluminal angioplasty and stenting
      with medical treatment for claudicants who have superficial femoral artery
      occlusive disease.
AB  - The outcomes of medical management of peripheral vascular disease localized to
      the superficial femoral artery (SFA) were compared with those obtained by
      percutaneous transluminal angioplasty (PTA) with or without stenting in a review
      of selected studies. The natural history of localized SFA disease is favorable,
      with major amputation rates less than 10% and revascularization in only 18% of
      patients over a 10-year interval. Conservative treatment of claudicants shows
      increases (150%) in walking distance if the ankle brachial index (ABI) is over
      0.6 and patients stop smoking. Analysis of 10 trials (882 patients) of PTA with
      or without stenting found that the overall primary patency rates at 12 months
      were 71.1% for PTA plus stenting and 58.3% for PTA alone. Technical success with
      PTA with or without stenting is over 90%, and early results at 6 months are
      superior to those with exercise. In three randomized controlled trials, however,
      the difference between PTA and medical treatment at 2 years, whether measured by
      walking distance or ABI, was not significant, nor was the quality of life. For
      long-term improvement in walking distance (> 1 year) in the claudicant,
      intervention is not superior to medical treatment and a monitored exercise
      program. Consideration should be given to including a nonintervention control
      group and 2-year outcomes in the evaluation of new SFA stents.

PMID- 16956475
TI  - Pain associated with carotid artery surgery performed under carotid plexus block:
      preemptive analgesic effect of ketorolac.
AB  - Carotid artery surgery (CAS) performed under cervical plexus block is frequently
      associated with significant intra- and postoperative pain. To evaluate whether
      preoperative administration of ketorolac may improve analgesia in this type of
      surgery, 80 patients scheduled for CAS under cervical plexus block were randomly
      allocated to receive intravenously either 30 mg of ketorolac or placebo 30
      minutes before surgery. Verbal rating scale pain scores during surgery and 3 and
      6 hours after surgery, the number of patients requiring additional analgesia, and
      the total analgesic consumption both during and within 6 hours after surgery were
      significantly lower, whereas the time to first postoperative analgesia was
      significantly shorter in the ketorolac group than in the control group. The
      results of this prospective, randomized, double-blind study show that a single 30
      mg dose of ketorolac administered intravenously 30 minutes before surgery reduces
      intraoperative pain and preempts postoperative pain in patients undergoing CAS
      under carotid plexus block.

PMID- 16956477
TI  - Do carotid surface irregularities correlate with the development of
      cerebrovascular symptoms? An analysis of the supporting studies, the opposing
      studies, and the possible pathomechanism.
AB  - Carotid plaque surface morphology appears to play a controversial role in the
      occurrence of cerebrovascular symptoms, that is, amaurosis fugax, transient
      ischemic attacks, and episodes of stroke. A number of researchers favor a strong
      association between the morphologic abnormalities of the carotid plaque surface
      and the development of cerebrovascular symptoms. The supporters of this theory
      have demonstrated that surface contour irregularities not only are important
      potential sources of flow abnormalities but also contribute significantly to the
      development of ischemic neurologic symptoms through plaque fragmentation,
      microthrombi formation, and atheroembolism. However, opposers of this theory also
      exist. The main arguments for and against this theory, as well as the possible
      underlying pathomechanism linking the morphology of the carotid plaque surface
      with the development of cerebrovascular symptoms, are outlined. Detection of
      carotid surface abnormalities with the aid of angiography or color-flow duplex
      ultrasonography should play a major role in the early identification of patients
      at increased risk, this way aiding prompt correction of these usually clinically
      silent but potentially hazardous lesions.

PMID- 16956478
TI  - Adjunctive pharmacologic use in carotid endarterectomy: a review.
AB  - Although carotid endarterectomy (CEA) is now widely accepted as the surgical
      therapy for carotid stenosis, the role of and indications and evidence for many
      pharmacologic agents that are used adjunctively in the perioperative setting have
      not been conclusively established. Aspirin (acetylsalicylic acid) is the
      pharmaceutical agent that has been studied most extensively in conjunction with
      CEA; other than aspirin and dextran, the use of many agents before, during, and
      after CEA has not been standardized. Prospective randomized trials are still
      needed to demonstrate efficacy, predict outcome, and determine the optimal use of
      these medications in their adjunctive use during CEA to improve patient care and
      obtain optimal surgical outcomes.

PMID- 16956479
TI  - Update on the diagnosis and management of popliteal aneurysm and literature
      review.
AB  - Popliteal artery aneurysms (PAAs) are the most frequent peripheral aneurysm with
      a significant morbidity if left untreated. Open surgical technique is still
      considered the gold standard; however the revolution in endovascular repair has
      proven to be a valid alternative option in selected patients. The role of
      endovascular treatment in PAA is still considered in its infancy. In addition,
      the indications for use of endovascular stents as compared to standard open
      surgery have not yet been fully defined and more studies are warranted to
      characterize the durability of this technique. This article describes the general
      principles of the natural history, clinical presentation, and long-term limb
      salvage and survival outcomes for patients with such aneurysms. It also details
      the features and results for the devices in current use and highlights the
      current consensus in the management of PAA.

PMID- 16956480
TI  - Superior mesenteric artery branch aneurysm with absence of the celiac trunk.
AB  - Superior mesenteric artery and pancreaticoduodenal artery aneurysms are rare.
      Agenesis of the celiac axis has only been reported four times. The reported
      etiologies of superior mesenteric artery and branch artery aneurysms include
      infection, atherosclerosis, inflammatory processes such as pancreatitis,
      dissection, collagen vascular disorders, polyarteritis nodosa, and trauma. We
      report an aneurysm of the superior mesenteric artery (SMA) branch, the inferior
      pancreaticoduodenal artery, arising in a patient with congenital absence of the
      celiac trunk. The patient presented with intermittent left upper quadrant pain
      without weight loss or change in bowel habits. The aneurysm was identified on
      abdominal computed tomography scan with angiographic confirmation of the aberrant
      anatomy. The patient was treated by aneurysmectomy and pancreaticoduodenal artery
      reconstruction with an interposition vein graft from the SMA. The patient
      recovered without complications and is asymptomatic with a patent vein graft 2
      years after operation.

PMID- 16956481
TI  - Reinforced long saphenous vein bypass graft for infrainguinal reconstruction
      procedures: case series and literature review.
AB  - Poor rehabilitation rates and the high-cost of managing postamputation patients
      justify an aggressive revascularization policy in critical lower limb ischemia.
      Endovascular therapy is our first choice for limb salvage in these patients.
      However there are patients for whom endovascular therapy is not feasible. When
      bypass is necessary, autologous vein is a superior conduit to synthetic material.
      However, varicosities usually contraindicate autologous vein bypass because of
      the risk of aneurysm formation, rupture and increased intimal hyperplasia
      compared with nonvaricose venous grafts. We report the use of varicosed long
      saphenous vein (LSV) with external Dacron support in infrainguinal bypass
      procedures for limb salvage, where endovascular therapy was not feasible. The
      external Dacron tube was not brought close to the distal anastomotic area itself.
      With a mean follow-up of 18 months, duplex ultrasonography and computed
      tomography angiography showed no evidence of stenosis of the reinforced vein
      segments or aneurysmal degeneration of the residual vein. External reinforcement
      with Dacron prosthesis allows the use of autogenous greater saphenous veins with
      varicose dilatation without compromising graft patency and limb salvage.

PMID- 16956482
TI  - Management of synchronous abdominal aortic aneurysm and complicating colorectal
      cancer.
AB  - Concomitant management of synchronous abdominal aortic aneurysm (AAA) and
      colorectal cancer (CRC) is mandatory in cases in which both entities are life
      threatening for the patient. The endovascular aneurysm repair (EVAR) method can
      contribute toward concomitant management by offering the avoidance of an
      otherwise threatening vascular graft infection. We present a case of a
      complicating CRC and a synchronous AAA, which were successfully treated at the
      same hospitalization. The AAA was treated first by EVAR, and the colon resection
      followed 3 days later. The patient's postoperative course was uneventful. EVAR,
      if the standard criteria are met, could comprise an alternative and reliable
      solution for treating concomitant AAA and CRC even in the acute setting.

PMID- 16956484
TI  - Amsterdam Acute Aneurysm trial: background, design, and methods.
AB  - The objective of the Amsterdam Acute Aneurysm Trial is to study the combined
      outcome of conventional emergency surgery versus endovascular treatment for
      ruptured abdominal aortic aneurysms. The design used was a multicenter randomized
      clinical trial conducted in two university hospitals and one teaching hospital in
      the Amsterdam region. The study included all patients with a ruptured abdominal
      aneurysm who were eligible for endovascular and conventional surgery. The primary
      end points were combined mortality and severe morbidity. The secondary end points
      were quality of life and cost-effectiveness. The background, design, and methods
      of this trial are presented, and the ethical and legal issues of this type of
      research are discussed.

PMID- 16956483
TI  - Stent-graft treatment of pseudoaneurysms and arteriovenous fistulae in the
      carotid artery.
AB  - The purpose of this study was to assess the safety and efficacy of stent-graft
      placement in the management of arteriovenous fistulae (AVF) and pseudoaneurysms
      (PAs) involving the carotid artery (CA). Twenty-two patients (16 men, 6 women)
      with a CA AVF (n = 5) or PA (n = 17) owing to a gunshot or stab wound, carotid
      endarterectomy, blunt trauma, a tumor, spontaneous dissection, or a central
      venous catheter were treated with percutaneous placement of stent grafts. The
      patients presented with tumor, bruit, headache, mouth and tracheostomy bleeding,
      transitory hemiparesis, seizure, or stroke. Diagnoses were made by using computed
      tomographic angiography (CTA) and digital subtraction angiography. Fourteen
      lesions were in the common CA; eight were in the internal CA. Homemade devices
      and stent grafts from a variety of manufacturers were employed. Follow-up
      evaluations included clinical, CTA, and Doppler ultrasound assessments. All
      patients had resolution of the PA or AVF. In one patient with a large petrous PA,
      acute occlusion of the CA developed after placement of three balloon-expandable
      stent grafts, but there were no neurologic complications because the circle of
      Willis was functional. During follow-up ranging from 2 months to 13 years,
      asymptomatic 90% stenosis owing to stent compression was observed on Doppler
      ultrasound and angiographic examinations in a patient with an autologous vein
      covered stent graft in the internal CA. Three other patients died of causes
      unrelated to stent-graft placement. In all other patients, the stent graft
      remained patent. Our results indicate that stent grafting is an acceptable
      alternative to surgery in the treatment of AVF and PAs in the CA.

PMID- 16956485
TI  - Long-term results of endovascular aneurysm repair with aortouni-iliac custom-made
      stent grafts.
AB  - The purpose of this study was to review the outcome of endovascular abdominal
      aortic aneurysm repair (EVAR) using custom-made aortouni-iliac (AUI) devices with
      femorofemoral bypass. Between June 1999 and March 2001, 23 consecutive patients
      (1 female, 22 male) at high risk of open aortic aneurysm repair underwent EVAR
      with custom devices in an AUI configuration. The mean follow-up was 37 months
      (range 2-72 months), and the mean age was 76.8 years (range 67.5-88.7 years).
      Increased surgical risk was evidenced by 92% and 69% of patients with significant
      pulmonary or cardiac disease, respectively. The preoperative mean aneurysm
      diameter (n = 23) 62 +/- 8.2 mm was significantly greater than the postoperative
      diameter, (n = 23) 54 +/- 16.4 mm. Ten endoleaks occurred. Migration of the stent
      graft occurred in 9% (n = 2). Secondary interventions were necessary in 23%,
      whereas tertiary interventions were required in 9%. Patients at high risk of open
      aneurysm repair received sufficient protection from aneurysm rupture with custom
      made AUI devices.

PMID- 16956486
TI  - Treprostinil sodium (Remodulin), a prostacyclin analog, in the treatment of
      critical limb ischemia: open-label study.
AB  - The purpose of this study was to assess the safety of continuous subcutaneous
      therapy with treprostinil sodium (Remodulin), a prostacyclin analog, and its
      effect on ischemic rest pain and ischemic wound healing in subjects with critical
      limb ischemia (CLI) and no planned revascularization procedure. This was a 12
      week, open-label, single-center pilot study enrolling 10 subjects (mean age 82.4
      years) with Fontaine stage III to IV (Rutherford class 4-6) peripheral arterial
      disease and ankle brachial indices less than 0.55. The primary end point was
      safety, and the secondary end points were the effects of treatment on ischemic
      rest pain, limb salvage, and wound healing. There was a 62% reduction in mean
      worst rest pain and a 57% reduction in mean average rest pain at week 12, with
      most subjects using less pain medication. Three subjects experienced complete
      healing of their wounds. No subject developed a new wound during the trial.
      Treprostinil was generally well tolerated. Subcutaneous infusion-site pain was
      the most frequently reported side effect, with one subject withdrawing from the
      study as a result. Jaw pain was reported by two subjects. One subject experienced
      two serious adverse events considered unrelated to treprostinil (cholecystitis
      and congestive heart failure). This study demonstrates that chronic, continuous
      subcutaneous treprostinil is safe and can be useful in the treatment of ischemic
      pain and wounds in subjects with CLI. Future controlled studies are needed to
      evaluate these effects and determine appropriate patient selection.

PMID- 16956487
TI  - Color-flow duplex hemodynamic assessment of runoff in ischemic lower limb
      revascularization.
AB  - The objective of this study was to evaluate the existence of hemodynamic arterial
      flow correlation between preoperative duplex scanning (DS) and intraoperative
      direct outflow resistance (IDOR) measurements in ischemic lower limb
      revascularization. Sixty-eight ischemic lower limbs were submitted to
      preoperative DS. Anatomic and hemodynamic arterial characteristics of the outflow
      system were recorded, and the results were considered in the distal anastomosis
      placement site decision making. IDOR measurements were obtained at the same
      arterial segment, and Pearson's correlation coefficient test was performed to
      study the preoperative DS power in predicting the intraoperative outflow
      resistance. DS was technically satisfactory and helped define the distal
      anastomosis site in 93.2% of the cases (supragenicular popliteal artery, 19
      [27.9%]; infragenicular popliteal artery, 10 [14.7%]; crural artery, 31 [57.4%]).
      A positive correlation could be found between preoperative DS and IDOR (0.450; p
      < .001). This correlation was particularly powerful in the crural artery (0.715;
      p < .001) when compared with the popliteal arterial segment (0.237; p = .192).
      Preoperative DS may help define the best distal arterial and outflow segment to
      be revascularized based on anatomic and hemodynamic parameters. There is a
      positive flow correlation between preoperative DS and IDOR that seems to be
      stronger in crural revascularization surgery.

PMID- 16956488
TI  - Occluded infrainguinal bypass graft: potential source of limb-threatening emboli.
AB  - Surgical bypass represents one of the chief treatment modalities for peripheral
      arterial occlusive disease. Despite improving techniques, graft occlusion
      accounts for the majority of these bypass failures. Once occluded, however, these
      grafts are thought to rarely pose a threat for future ischemic events. This
      report describes two patients with previously thrombosed grafts who subsequently
      presented with limb-threatening ischemia owing to peripheral embolization from
      the graft. Two patients with occluded grafts presented with ipsilateral limb
      threatening acute ischemia. Both of these patients developed severe acute limb
      threatening ischemia weeks to months after known graft thrombosis. Arteriography
      revealed peripheral embolization in each case. Both patients were operated on for
      disconnection of the thrombosed graft from the native circulation and have been
      free of recurrent symptoms. The occluded graft, although generally innocuous, can
      be a source of peripheral emboli, resulting in peripheral embolization and acute
      limb ischemia. Both patients in this report developed limb-threatening ischemia
      owing to embolization from the cul-de-sac of occluded prosthetic grafts. Due to
      the rarity of the condition and its associated morbidity and mortality, awareness
      and recognition of this phenomenon are critical. Operative disconnection is
      recommended if the embolism occurs downstream of the graft and no other embolic
      source can be identified.

PMID- 16956489
TI  - Endovascular treatment of a symptomatic suture aneurysm caused by an aortic
      isthmus restenosis.
AB  - After operative treatment of aortic isthmus stenoses, late complications, such as
      aneurysm formation or aortic restenosis, might occur, with relevant morbidity and
      mortality rates during open surgical reintervention. We report on the
      endovascular repair of a symptomatic suture aneurysm caused by an aortic isthmus
      restenosis by thoracic aortic stent graft implantation and additional
      intraoperative balloon dilatation. Based on our experience, endovascular repair
      of thoracic aortic aneuryms caused by native aortic isthmus stenosis or
      postcoarctation restenosis is a valuable treatment option, especially in
      symptomatic patients with an imminent risk of rupture or a difficult immediate
      transthoracic surgical approach. Long-term follow-up is required to assess the
      durability of the stent graft treatment.

PMID- 16956490
TI  - Nocardia asteroides-infected aneurysm of the aorta: case report and review of the
      literature.
AB  - Infected aneurysms of the aorta were first described as a result of septic emboli
      or contiguous spread from bacterial endocarditis and are usually caused by
      Staphylococcus or Salmonella species. We report a case of Nocardia-associated
      infected aneurysm of the native suprarenal aorta in an immunocompromised host.
      Surgical management consisted of placement of an interposition cryopreserved
      aortic homograft. Nocardia asteroides was identified on a microbiology specimen
      of the aorta and both microbiology and pathology specimens of the splenic tissue.
      To the best of our knowledge, this represents the first carefully documented,
      unique case of a Nocardia-infected aneurysm treated with homograft interposition.
      In addition, pathologic and microbiologic data are included from the postmortem
      examination 10 months later.

PMID- 16956491
TI  - Cystic adventitial disease of the iliofemoral artery: case reports and a short
      review.
AB  - Cystic adventitial disease is a rare disease affecting mainly young males. We
      describe two patients with this disease affecting the iliofemoral artery. These
      reports reemphasize the importance of keeping cystic adventitial disease as a
      differential diagnosis in young patients who present with leg ischemia.

PMID- 16956492
TI  - Atherosclerotic aneurysm formation in a lower extremity saphenous vein graft.
AB  - Saphenous vein is the most widely used conduit for arterial bypass procedures and
      aneurysms of the vein graft are rare. We report a true aneurysm of a reversed
      femoropopliteal saphenous vein graft implanted nine years earlier. Duplex
      ultrasonography identified an aneurysm of the saphenous vein graft and
      arteriography confirmed this finding. A consideration for endovascular coiling of
      the aneurysm was entertained, but no proximal "neck" on the aneurysm was present.
      The patient, therefore, underwent an uneventful resection of the aneurysm with
      end-to-end anastomosis. Histopathologic examination of the aneurysm demonstrated
      atherosclerotic degeneration with endothelial disruption, medial necrosis, and
      fibrous proliferation. The cause of a saphenous vein graft aneurysm is rare and
      unknown. The management of vein graft aneurysms, however, should be subject to
      the same criteria that apply to other aneurysms because once vein graft dilation
      occurs, it is followed by a rapid increase in size, which may lead to possible
      rupture.

PMID- 16956493
TI  - Postendarterectomy common carotid artery pseudoaneurysm.
AB  - Pseudoaneurysm (PSA) formation is an uncommon complication in carotid surgery.
      PSA of the carotid artery requires surgical or endovascular treatment to prevent
      PSA thrombosis, embolization from the thrombotic material within the PSA,
      hemorrhage after rupture, or compression on the adjacent structures. We present a
      case of a symptomatic common carotid PSA that occurred 14 months after routinely
      performed eversion carotid endarterectomy.

PMID- 16956496
TI  - [On prognostic indicators in acute lymphoblastic leukemia in children].

PMID- 16956497
TI  - [Twenty years of treating childhood acute lymphoblastic leukemia].
AB  - BACKGROUND: Conventional prognostic factors for relapse in patients with acute
      lymphoblastic leukemia (ALL) are the main basis of risk-stratified treatments.
      OBJECTIVES: To analyze conventional risk factors for relapse and design a
      predictive model for relapse in our series, after 20 years of experience in
      treating ALL. PATIENTS AND METHOD: We performed a multivariate analysis of
      conventional prognostic factors in the treatment of ALL in our unit and compared
      them with the risk groups in the Berlin-Frankfurt-Munster (BFM-ALL) treatment
      protocols. RESULTS: Between 1984 and 2004, 232 children were diagnosed with ALL
      and treated according to the different versions of the BFM protocols (BFM83,
      BFM86, BFM90 and BFM95) at the Hospital Nino Jesus, Madrid, Spain. The event-free
      survival for all patients was 79.4 % (95 % CI: 72.7-85.4). Overall survival among
      patients who relapsed was 10.72 % (95 % CI: 6-27.3). The only significant
      prognostic factor for relapse identified by multivariate analysis was leukocyte
      [white blood cell (WBC)] count higher than 80,000/ml at diagnosis (hazard ratio
      [HR]: 4.63; 95 % CI: 1.61-13.3; p 5 0,004). The sensitivity and specificity of
      WBC in predicting relapses were 31.4 % and 87.5 %, respectively. The sensitivity
      and specificity of BFM risk group stratification in predicting relapses were 25
      and 85.9 respectively. CONCLUSIONS: A leukocyte count at diagnosis higher than
      80,000/ml and BFM risk-stratified treatment have insufficient sensitivity and
      specificity to identify relapses.

PMID- 16956498
TI  - [Role of rhinovirus in respiratory tract infections in hospitalized children].
AB  - BACKGROUND: Rhinovirus is a recognized cause of common cold and has been shown to
      cause asthma exacerbations in adults and children. The burden of rhinovirus
      infections in hospitalized children has not been described in Spain. OBJECTIVE:
      To describe confirmed rhinovirus infections in children hospitalized for
      respiratory tract infection in a secondary public hospital. PATIENTS AND METHODS:
      We performed a prospective descriptive study in children admitted to hospital
      with fever or respiratory tract infection and with a positive isolation of
      rhinovirus in nasopharyngeal washings between September 2004 and July 2005.
      Virological diagnosis was made with direct immunofluorescent assay and/or reverse
      transcription-polymerase chain reaction in specimens obtained from nasopharyngeal
      washings. The clinical characteristics of the patients were analyzed. RESULTS:
      There were 76 children with rhinovirus infection, representing 25 % of admissions
      in 304 children with fever or respiratory tract infection. Rhinovirus was the
      second most frequent viral agent identified after respiratory syncytial virus
      (RSV) (29.9 % of admissions). Fifty-four children (71.1 %) were under 2 years of
      age. The most frequent clinical diagnoses were recurrent wheezing in 60.5 %,
      bronchiolitis in 23.7 %, pneumonia in 7.9 %, and upper respiratory tract
      infection in 5.3 %. Fever > 38 degrees C was present in 57.9 % of the patients
      and radiologic infiltrate was found in 23.7 %. Oxygen saturation less than 95 %
      was found in 43.4 % of the patients. Of 22 children aged more than 2 years, a
      diagnosis of asthmatic crisis was made in 21. CONCLUSIONS: Rhinoviruses were
      frequently identified in hospitalized children with respiratory tract disease and
      were the second most common viruses after RSV. In our series, it was the most
      frequent cause of recurrent wheezing in hospitalized children and the second most
      common cause in infants.

PMID- 16956499
TI  - [Clinical and epidemiological characteristics of influenza A virus infection in
      children aged less than 7 years old in primary care].
AB  - INTRODUCTION: The aim of this study was to describe the clinical and
      epidemiological features of confirmed influenza A virus infection in patients
      aged less than 7 years old. PATIENTS AND METHODS: We performed a retrospective,
      descriptive study of the clinical and epidemiological features of influenza A
      virus infection in patients aged less than 7 years old attending three primary
      care centers during the 2003-2004 influenza season. Patients with influenza A
      infection confirmed by immunofluorescence, cell culture, or polymerase chain
      reaction were interviewed to obtain clinical and epidemiological data on their
      disease. RESULTS: Influenza A virus was detected in 47 patients aged between 5
      months and 7 years (mean: 37.3 +/- 5.7 months). Of these, 35 children (74.4 %)
      were aged between 0 and 4 years. The most frequent symptoms were fever (100 %),
      cough (95.7 %), and rhinorrhea (76.6 %). Gastrointestinal symptoms were present
      in 40.4 % of the patients. The mean duration of fever was 5.2 +/- 1.8 days (range
      2-8). Complications occurred in nine patients (19.2 %). The frequency of
      influenza-like disease in parents was 9.1 % (8/88) at diagnosis of the index case
      and was 23.9 % (21/88) immediately after the episode in the child (p 5 0.01). The
      mean number of days of absence from school was 7.5 +/- 3.6 days. CONCLUSIONS: The
      mean age of our patients confirms that influenza is a frequent disease in infancy
      and childhood. The results demonstrate that the infection is transmitted from
      children to parents in the household setting, since the frequency of influenza
      like symptoms in adults increases after influenza episodes in children.

PMID- 16956500
TI  - [Epidemic outbreak of tuberculosis in a daycare centre in Zaragoza (Spain)].
AB  - OBJECTIVE: To describe the clinical and radiological features, diagnosis, and
      treatment of an epidemic outbreak of tuberculosis in a daycare centre in
      Zaragoza. MATERIAL AND METHODS: The index case was a teaching assistant with a
      late diagnosis of bacilliferous tuberculosis. Mantoux testing was carried out in
      all children. In those with a positive Mantoux test, a chest X-ray was performed.
      Children with an abnormal chest X-ray underwent microbiological investigations.
      RESULTS: Among all the children in the daycare center, the Mantoux test was
      positive in 11 children. Chest X-ray was abnormal in 10 children. Of these, seven
      (70 %) were symptomatic. Chest X-ray showed dense opacification in nine children
      (90 %) and mediastinal lymph adenopathy in five (50 %). Three children (30 %) had
      lobar atelectasis requiring bronchoscopy and subsequent steroid therapy.
      Bacilloscopy was positive in only one child. Gastric juice culture was positive
      in seven children and the amplified Mycobacterium tuberculosis direct test was
      positive in a further seven. All microbiological investigations were negative in
      only one child. CONCLUSIONS: Establishing a definitive diagnosis of tuberculosis
      in children remains difficult and frequently relies on a constellation of
      clinical findings, radiology and epidemiology in children with a positive Mantoux
      test. The amplified Mycobacterium tuberculosis direct test has high sensitivity
      and provides fast results. Epidemic outbreaks continue to be frequent in Spain.
      Study of contacts shows high efficiency in controlling outbreaks.

PMID- 16956501
TI  - [The tuberculin skin test in a healthy child program: should we change our
      practice].
AB  - BACKGROUND: The Healthy Child Program and the Preventive Activities and Health
      Promotion Program involve systematic tuberculin skin testing at distinct ages
      according to different programs, with variable evaluation of its effectiveness.
      OBJECTIVE: To evaluate the tuberculin skin test performed in healthy children
      within the ongoing basic health program in order to determine whether our
      activity is effective in detecting latent tuberculin infection. MATERIAL AND
      METHODS: A prospective observational study was performed. POPULATION: Mantoux
      test performed in children aged 15 months to 14 years during regular health
      examinations in 22 primary care pediatric clinics over a 12-month period in
      southern Pontevedra in Spain (catchment population 300,613 inhabitants according
      to the official census data in January 2003, with 472,444 health cards).
      Descriptive study and univariate analysis were carried out. RESULTS: We studied
      2,530 children with a mean age of 51.25 months (95 % CI: 49.38-53.13). Eight
      positive Mantoux tests were registered (0.36 %). There were three positive
      results in children aged less than 3 years, two positive results in children aged
      between 4 and 9 years old (all were immigrants) and the remaining positive
      results were registered in children between 10 and 14 years of age. CONCLUSIONS:
      Given that the tuberculin skin test is a good screening test despite its
      limitations in the control of latent tuberculin infection in children, its
      indications should be adjusted to ever-changing epidemiological characteristics.
      According to the results obtained in this study and considering the prevalence of
      tuberculosis in our environment, we propose that the systematic application of
      the Mantoux test be discontinued except in children from countries with a high
      incidence of this disease or risk factors. However, we also recommend that
      systematic Mantoux testing in adolescence (12-14 years of age) be maintained,
      when vaccination and various medical examinations are carried out.
      Epidemiological studies in this age group should simultaneously be performed.

PMID- 16956502
TI  - [Relationship between lipid profile and body mass index. Five-year follow-up in
      children aged 6-11 years old. The Rivas-Vaciamadrid study].
AB  - BACKGROUND: To study the relationship between lipid profile and body mass index
      (BMI) in children after a 5-year follow-up. METHOD: A total of 281 children were
      evaluated at the ages of 6 and 11 years. Total cholesterol (TC), triglycerides
      (TG), high-density lipoprotein cholesterol (HDL-C), and apoproteins A1 (Apo A)
      and B100 (Apo B) were measured. Low-density lipoprotein cholesterol (LDL-C) was
      determined and the Apo B/Apo A, TC/HDL-C, LDL-C/HDL-C indexes, and the
      atherogenic index were calculated. BMI was also calculated (BMI 5 kg/m2).
      Evolution parameters were calculated (EVO 5 value 11 years - value 6 years).
      Associations between BMI and lipid profile were studied. RESULTS: The prevalence
      of obesity (according to the criteria of the International Obesity Task Force)
      was 4.98 % (6 years) and 16,72 % (11 years). In children who were in the fourth
      BMI quartile at the age of 11 years, LDL-C/HDL-C and TC/HDL-C levels were
      significantly higher and than those in children in the first quartile but HDL-C
      and Apo A levels were lower. A significant positive correlation was found between
      the evolution of BMI and the four indexes studied and TG, but this correlation
      was negative for HDL-C and Apo A. The evolution of the indexes was positive in 11
      year-old obese children and negative in nonobese children. CONCLUSIONS: Lipid
      profile was worse in 11-year-old children in the fourth BMI quartile than in the
      remaining children. Obese children had higher values of the indexes studied,
      supporting the importance of obesity as a cardiovascular risk factor.

PMID- 16956503
TI  - [Endemic goiter and iodine deficiency: are they still a reality in Spain].
AB  - OBJECTIVE: To estimate the prevalence of goiter and iodine deficiency in a health
      district in the Autonomous Community of Valencia, given the absence of data in
      this region of Spain. MATERIAL AND METHODS: We conducted a descriptive,
      epidemiologic, cross-sectional study, stratified by age and sex, in four interior
      regions of the province of Valencia. We selected students aged from 6 to 14 years
      old in 20 centers. Thyroid examination was performed by means of palpation and
      inspection (goiter > or = 0B). Urinary iodine excretion was analyzed in a routine
      urine sample. Sociodemographic and anthropometric data, as well as nutritional
      iodine status, were recorded in a standardized survey. In children with goiter,
      thyroid-stimulating hormone (TSH), free T4, and antithyroid antibodies were
      determined. RESULTS: We studied 928 children (478 boys and 450 girls). The
      prevalence of goiter was 33.7 % (95 % CI: 30.7-36.9 %). There were no significant
      differences in the prevalence of goiter by age or sex, but an inverse correlation
      was detected between the prevalence of goiter and parental socioeconomic
      position. Mean urinary iodine excretion was 155 .g/l, with no significant
      correlation with the prevalence of goiter. In children with goiter, 13 had
      positive antithyroid antibodies, 18 had high TSH (subclinical hypothyroidism),
      and one had suppressed TSH (subclinical hyperthyroidism). CONCLUSIONS: There is
      endemic goiter in the region studied. Urinary iodine levels were in the normal
      range and could be interpreted as indicating a transition phase to an improvement
      in iodine deficiency. Autoimmune diseases would only explain 4 % of cases of
      goiter.

PMID- 16956504
TI  - [Recommendations of the Vaccine Advisory Committee of the Spanish Association of
      Pediatrics: influenza vaccination campaign 2006-2007].
AB  - The recommendations of the Spanish Association of Pediatrics on influenza
      vaccination in the pediatric age group for the 2006-2007 season are presented.
      Influenza has special characteristics in children due to the high morbidity it
      carries. Moreover, children constitute the most frequent source of transmission.
      The risk factors supporting influenza vaccination in children and the need for
      immunization in persons living with high-risk children are discussed. The
      advisability of extending vaccination in health workers, and specifically to
      pediatricians and medical personnel in contact with sick children is stressed.
      The composition of the vaccine for the 2006-2007 seasons, the schedules and
      dosages in children depending on age, and the contraindications to vaccination
      are specified. Finally, the premises required to recommend universal vaccination
      in young children in Spain as a strategy to reduce morbidity due to this epidemic
      in children and adults are discussed.

PMID- 16956505
TI  - [Transitory neonatal diabetes mellitus and pericentric chromosome 9 inversion].
AB  - Neonatal diabetes mellitus is an infrequent carbohydrate metabolism disorder with
      an estimated incidence of approximately one case every 400,000 to 600,000 live
      newborns. We present the case of a 1-month-old girl with irritability, polyuria,
      and a 24-h history of eagerness to feed, without fever or other associated
      symptoms. The patient's karyotype, obtained by amniocentesis, was 46XX with a
      pericentric chromosome 9 inversion. Her birth weight and length were 2,230 g (
      2.65 SD) and 46 cm (-1.8 SD), respectively. Glycemic determinations during the
      first 72 h of extrauterine life oscillated between 90 and 157 mg/dl. Physical
      examination revealed general involvement, skin and mucosal pallor, evident signs
      of dehydration, and impaired awareness. Laboratory tests revealed glycemia: 1552
      mg/dL, pH 7.16, pCO2: 23.7 mmHg; bicarbonate: 8.1 mEq/L, base excess: -19.1, and
      positive ketonemia. After initial stabilization, the patient was treated with
      intravenous fluids and continuous intravenous regular insulin infusion (initial
      dose 0.03-0.05 IU/kg/h). After intensive treatment, breast feeding was restored
      and a short-acting insulin analog was administered subcutaneously after every
      feed (0.1 to 0.3 IU according to capillary glycemic determinations). Insulin
      requirements decreased and were discontinued when the infant was 5 months old.
      Currently, the patient is 2 years and 7 months old and her glycemia and
      glycosylated hemoglobin levels are normal. Anti-islet (ICA and GAD) and anti
      tyrosin phosphatase (IA2) antibodies were absent, as were mutations in the
      glucokinase gene (GCK).

PMID- 16956506
TI  - [Acral eruptive nevi after chemotherapy in children with acute lymphoblastic
      leukemia].
AB  - Eruptive melanocytic nevi have mainly been associated with blistering cutaneous
      diseases and with immunosuppression, particularly after renal allograft
      transplantation, hematological neoplasms, or HIV infection. Thus,
      immunosuppression has been suggested to increase the possibility of melanocyte
      proliferation. We report two cases of children with acute lymphoblastic leukemia
      who, after receiving chemotherapy, developed severe motor polyneuropathy, and
      sudden onset of multiple melanocytic nevi on the soles.

PMID- 16956507
TI  - [Dilated cardiomyopathy secondary to atrial ectopic tachycardia].
AB  - Ectopic atrial tachycardia is an uncommon cause of supraventricular tachycardia
      in children. It can resolve spontaneously or induce dilated cardiomyopathy. It is
      important to recognize this entity as a reversible cause of dilated
      cardiomyopathy, characterized by the presence of an abnormal focus located in the
      atrial myocardium and distinct to sinus node. Treatment strategies include the
      use of antiarrhythmic drugs, radiofrequency ablation, and, in patients refractory
      to medical treatment, surgical resection of the ectopic focus. We describe a
      patient with dilated cardiomyopathy due to an atrial ectopic focus and its
      resolution after medical treatment.

PMID- 16956508
TI  - [Influenza prevention in the pediatric age group].

PMID- 16956509
TI  - [Bilateral ovarian teratoma].

PMID- 16956510
TI  - [Toxic thyroid adenoma and hyperthyroidism].

PMID- 16956511
TI  - [Rhabdomyosarcoma of the bile ducts as a cause of obstructive jaundice].

PMID- 16956512
TI  - [Psoriasis and anxiety: marked improvement after anxiolytic therapy].

PMID- 16956513
TI  - [Recurrent pericarditis, colchicine and pericarditic pain without evident
      disease].

PMID- 16956514
TI  - [Loss of language].

PMID- 16956515
TI  - [Hand dermatitis].
AB  - Hand dermatitis is a common skin disease that often has a chronic and relapsing
      course. Several subtypes of hand dermatitis have been described. In this review,
      we describe the clinical characteristics of each form of hand eczema, laboratory
      tests helpful in the diagnosis, and treatment options for this condition.

PMID- 16956516
TI  - [Sensitization to Lyral].
AB  - INTRODUCTION: Lyral is a fragrance that is present in many cosmetic products. It
      has turned into an emergent allergen during the last years. In studies carried
      out in other European countries, the prevalence of sensitization to Lyral has
      been found to be 1.9-2.7 %, but it is unknown the prevalence in Spain, as well as
      the need to include it or not in the standard series of the Spanish Group of
      Contact Dermatitis (GEIDC). METHODS: We have patch-tested to Lyral all patients
      with suspicion of contact dermatitis of any origin who attended our Service
      between April and May-2005. RESULTS: From a total of 170 patients included in our
      study, 2 of them had a sensitization to Lyral (1.2 %). One of these two patients
      had an axillae contact dermatitis caused by a deodorant containing Lyral. The
      other patient was a masseur-woman with a contact dermatitis on both hands, with
      periods of dissemination to upper extremities and trunk, and who used several
      cosmetics products for private reasons and during her job. CONCLUSION: Although
      the sample of this study is quite small, we think that the results allow to
      suspect that Lyral is one of the main allergens, or even the most important, in
      causing allergic contact dermatitis to fragrances in our environment. Therefore,
      we believe that we must raise the inclusion of Lyral in the standard series of
      GEIDC, either as independent allergen, or including it in a new mixture of
      fragrances.

PMID- 16956517
TI  - [Lipomembranous panniculitis: clinicopathologic correlation of 8 cases].
AB  - INTRODUCTION: The term lipomembranous panniculitis refers to a chronic
      inflammation of the subcutaneous cell tissue, probably representing a non
      specific type of ischemic necrosis of the fatty tissue, common to several
      complaints. It is characterized by painful sclerotic subcutaneous deposits,
      located in the lower legs of obese, middle-aged woman, with a history of vascular
      insufficiency and stasis dermatitis. The condition may also appear in association
      with other inflammatory disorders. METHODS: This paper is a review of all cases
      of lipomembranous panniculitis diagnosed at the Skin Histopathology Laboratory at
      Santa Maria Hospital, Lisbon, from 1985-2005. In the histopathological study, the
      associated clinical processes were retrospectively analyzed and the risk
      factors/associated pathologies re-evaluated. RESULTS: Eight patients were
      identified, all women, and with an average age of 49. Over half the patients were
      overweight. In most cases the lesions had been evolving for over 6 months and
      were associated with chronic venous insufficiency of the legs, both from a
      clinical point of view (7 patients) and a histopathological point of view (6
      patients). In two of the cases, the lesions occurred in patients with connective
      tissue disorders. CONCLUSION: Great variability was observed with regard to the
      clinical morphology of the lesions, the proposed diagnoses and prescribed
      treatments, all of which possibly highlight the non-specific nature of the
      process.

PMID- 16956519
TI  - [Ofuji's disease: description of a case].
AB  - Eosinophilic pustular folliculitis (EPF) is a rare, chronic disease of unknown
      cause, characterized by itchy papules or pustules and an infiltration of
      eosinophiles in the biopsy. EPF occurs rarely outside Japan and very few cases
      have been described in non-Japanese race people. The causes of the disease and
      its definitive treatment have not yet been established. In our patient, the
      presence of subcorneal pustules in the biopsies initially favored a diagnosis of
      pustulosis and several biopsies were necessary before a diagnosis of EPF was
      reached. A new case of EPF recently presented at our clinic and we have carried
      out an extensive revision of the disease.

PMID- 16956518
TI  - [Two HHV8-related illnesses in a HIV-negative patient: Kaposi's sarcoma and
      multicentric Castleman's disease. Response to treatment with Rituximab and CHOP].
AB  - Human herpes virus 8 (HHV8) was discovered in 1994 in the biopsy of a Kaposi's
      sarcoma in a patient with AIDS. Since then it has been identified in all variants
      of Kaposi's sarcoma and in another two rare disorders: multicentric Castleman's
      disease and primary body-cavity based lymphomas. The case discusses a 68 year
      old, HIV-negative male patient, presenting Kaposi's sarcoma for one year and
      being monitored by dermatology, who presented for weakness, anorexia and fever.
      On examination, he was found to have adenitis of the lymph nodes in his neck,
      underarm and groin. A biopsy on one of the swellings led to findings
      characteristic of multicentric plasma cell variant Castleman's disease. Blood
      tests for HHV8 and HIV were carried out, resulting positive and negative
      respectively (IgG anti-HHV8 positive, title 1/640, indirect immunofluorescence).
      PCR amplification showed HHV8 in peripheral blood. Patient received 8 cycles of
      CHOP and rituximab, leading to complete disappearance of the adenitis and general
      symptoms, with no worsening of his Kaposi's sarcoma. Patient remained in complete
      remission for 10 months after treatment. This paper discusses the case of a HIV-,
      HHV8+ patient, diagnosed with classic Kaposi's sarcoma, who developed
      multicentric plasma cell variant Castleman's disease. The coincidence of two or
      more HHV8-related illnesses in a HIV-negative patient has rarely been described
      in medical literature. Treatment with rituximab combined with CHOP chemotherapy
      was effective in this case, and no worsening of the patient's KS was observed.

PMID- 16956520
TI  - [Three cases of early neurosyphilis in HIV patients].
AB  - In spite of the relative control of the disease in the late 20th century,
      syphilis, like other sexually transmitted diseases, has undergone a strong
      resurgence in recent years in the large urban centers of Europe and the US. Many
      patients with syphilis are also HIV+. The association between the two diseases
      may modify the clinical evolution of syphilis and increase the incidence of
      neurological disorders. We discuss the cases of three patients diagnosed with
      both diseases last year, with neurological presentation of syphilis occurring
      early and ophthalmic or cochlear vestibular involvement. This recent outbreak of
      syphilis seems to lead to an increase in the number of atypical cases presenting
      in our daily practice, where we must be prepared for early diagnosis and
      treatment.

PMID- 16956521
TI  - [Malignant syphilis in patients with human immunodeficiency virus (HIV)].
AB  - Malignant or noduloulcerative syphilis is an infrequent variant of secondary
      syphilis which appears in HIV+ patients. It is associated with fever, general
      malaise and skin lesions in the form of pustules or ulcerative scabs. Histology
      studies on the lesions show a perivascular infiltration of plasma cells and a
      formation of granuloma of giant and epitheloid cells. Most patients test positive
      for syphilis. We discuss the case of a 37-yar-old man who attended our service
      complaining of fever and scabby nodular lesions all over his skin. Blood testing
      confirmed that he had syphilis and HIV. The patient responded rapidly to
      penicillin treatment, with remittance of his fever. The skin lesions disappeared
      after 8 weeks. The rareness of malignant syphilis and its unusual clinical
      manifestation is a challenge to medical personnel. This diagnosis ought to be
      considered in HIV+ patients with fever and ulcerative skin lesions. Penicillin is
      the treatment of choice.

PMID- 16956522
TI  - [Persistence of the omphalomesenteric duct. Childhood differential diagnosis of
      umbilical granuloma].
AB  - The omphalomesenteric duct is an embryonic structure which communicates the
      vitelline duct with the midgut. It normally disappears between the fifth and
      ninth weeks of intrauterine life. Anomalies related with the total or partial
      absence of this involution are show in 2 % of the population. We report a case of
      persistence of the omphalomesenteric duct and review the bibliography to
      establish the differences between this anomaly and umbilical granuloma, which is
      the main differential diagnosis.

PMID- 16956523
TI  - [Solitary giant cell collagenoma].
AB  - Collagenoma or collagen nevus of the connective tissue is a hamartomatous
      malformation of the dermis, characterized by a proliferation of normal collagen
      tissue. This may be congenital or acquired, solitary or multiple, hereditary or
      sporadic. The solitary type are sporadic, not associated with any disease, and
      may appear on any part of the body. Histology studies show an increase of
      collagen fibers in the dermis and a variable decrease in elastic fibers. We
      discuss the case of a child with a solitary giant cerebriform collagenoma on the
      lumbar region of her back.

PMID- 16956524
TI  - [Papules, vesicles and blisters in a patient with chronic lymphatic leukemia].

PMID- 16956525
TI  - [Repetitive ulcerative lesions].

PMID- 16956526
TI  - [Basocellular cancer of the vulva: a rare location for one of the most frequent
      types of skin cancer].

PMID- 16956527
TI  - [Vaccination of health-care personnel].

PMID- 16956528
TI  - [Influenza vaccination in healthcare workers. Why are some vaccinated whereas
      others are not].
AB  - BACKGROUND AND OBJECTIVE: Influenza vaccination is indicated in health
      professionals. Nevertheless, vaccination coverage in healthcare workers tends to
      be low. This paper determines the reasons why some workers are vaccinated whereas
      others are not and investigates what type of intervention can modify the latter
      attitude. METHOD: This was a cross-sectional descriptive study using a
      questionnaire survey. SETTING: workers at Hospital General Universitario de
      Alicante (Alicante, Spain). Absolute frequencies and relative frequencies
      expressed in percentages were calculated for each of the variables studied.
      Results were analyzed considering the professional categories of the persons
      involved and the departments where they worked. RESULTS: The reasons for
      influenza vaccination stated by hospital workers were to protect their health
      (65.6%), the belief that vaccination is beneficial (45.7%), and to avoid
      transmitting influenza to their patients (42.5%), and to their own families
      (39.8%). The main reasons for not undergoing vaccination were to avoid medication
      (17.9%), confidence in their own defenses (17%), or fear of the secondary effects
      of the vaccine (16.8%). CONCLUSION: The main reason given by hospital personnel
      for undergoing vaccination was to protect their own health and that of their
      family and patients. The reasons most frequently given for not undergoing
      vaccination were based on possible side effects of the vaccine, the conviction of
      not being part of a high-risk group, and doubts about the effectiveness of the
      vaccine as a protective agent. Many of the reasons given for not undergoing
      vaccination were based on erroneous beliefs and should be taken into account when
      designing strategies to increase influenza vaccination coverage among health
      personnel.

PMID- 16956529
TI  - [Antimicrobial susceptibility of uropathogens and outcome following antibiotic
      treatment for urinary tract infections in primary health care].
AB  - BACKGROUND AND OBJECTIVE: An increase in the resistance to antimicrobial agents
      among bacteria causing urinary tract infections (UTI) has been reported. The aim
      of this study was to relate uropathogen susceptibility to prescribed antibiotics
      for UTI to the clinical outcome after therapy in primary health care patients.
      METHODS: A prospective longitudinal study, including 118 women diagnosed with UTI
      was carried out in primary health care centers. The results of urine culture,
      antimicrobial susceptibility testing and the prescribed antibiotic treatment were
      recorded. The patients' clinical outcome and the results of follow-up urine
      cultures after therapy were also recorded. RESULTS: The uropathogens isolated
      were susceptible to the prescribed antibiotic in 86% of patients. Clinical
      improvement at two weeks was observed in 91% of patients with bacteria sensitive
      to the prescribed antibiotics and 7% of patients with resistant bacteria (P =
      0.06). At 4-6 weeks, there were no clinical symptoms in 88% of patients with
      sensitive bacteria and 71% of patients with resistant bacteria (p = 0.23). In
      follow-up urine cultures, bacteria had been eradicated in 74% of patients with
      sensitive bacteria and 50% with resistant bacteria (p = 0.34). CONCLUSIONS: The
      majority of women diagnosed with UTI in primary health care had uropathogens
      sensitive to the prescribed antibiotic and treatment was effective at short term
      in this study. The results of antimicrobial susceptibility testing were not
      always related to the clinical outcome; bacterial resistance may overestimate the
      risk of therapeutic failure in UTI.

PMID- 16956530
TI  - [Immunological effectiveness of the nucleoside/nucleotide analog combinations,
      tenofovir + lamivudine, didanosine + lamivudine and tenofovir + didanosine, in
      patients with HIV infection and sustained viral suppression].
AB  - BACKGROUND: Several recent studies have shown that the combination of ddI plus
      TDF can produce an unexpected drop in CD4 cell counts, even after correcting the
      ddI dose. OBJECTIVE: Comparative study of the immunological effectiveness of
      various once-daily NRTI backbones (ddI plus TDF, ddI plus 3TC or TDF plus 3TC) in
      antiretroviral-experienced HIV-infected patients achieving viral suppression
      (PCR, HIV-RNA < 50 copies/microl). METHODS: Prospective cohort study of 48 weeks'
      duration following viral load suppression with any of the NRTI combinations
      studied. The main outcome variable was the increase in CD4+ lymphocyte count from
      the time that viral load was undetectable or treatment was changed for
      simplification or toxicity (baseline) up to 48 weeks of follow-up. Differences
      between the assigned therapies were compared. The variables included in analysis
      were age, sex, risk group, HCV infection, clinical categories of HIV (CDC
      criteria), lowest CD4 cell count, reason for change of NRTI backbone, type of
      antiretroviral treatment (PI, NNRTI, or 3 NRTI) and duration of suppressed viral
      load. RESULTS. Regimens including ddI plus TDF showed significant decreases in
      CD4 cell counts with adjustments by type of HAART, reason for change, and
      duration of suppressed viral load. In patients treated with TDF + 3TC, CD4 count
      increased by 160 cel/microl (95% CI, 53-266) more than in patients treated with
      TDF + ddI; and in patients receiving ddI + 3TC, CD4+ count increased by 138
      cel/microl (95% CI, 25-266) more than in patients receiving TDF + ddI.
      CONCLUSIONS: The ddI plus TDF backbone seems unadvisable because of the lower
      associated CD4 cell counts, and because it is poorer than the other options from
      the immunological standpoint.

PMID- 16956531
TI  - [Descriptive study of hepatitis outbreaks occurring in Catalonia (1999-2003)].
AB  - BACKGROUND AND OBJECTIVE: The currently low endemic level of hepatitis A in Spain
      favors manifestation of the disease as outbreaks among specific risk groups. The
      aim of this study is to analyze the hepatitis A outbreaks investigated in
      Catalonia (Spain) during the period of 1999 to 2003. METHODS: The criteria for
      including an outbreak were defined and outbreaks were classified according to the
      type of transmission. The variables analyzed were space, time, socio-demographic
      parameters, setting, risk factors, and preventive measures adopted. The incidence
      rate and rate ratio were calculated according to age and sex. RESULTS: Among 74
      outbreaks, 73 fulfilled the inclusion criteria. Most outbreaks involved person-to
      person transmission (83.8%) and the rest had a common source of infection
      (14.9%). In total, 334 cases were included (cumulative incidence 1999-2003: 5.27
      per 100,000 inhabitants), with an average age of 24.5 years. The settings
      yielding the most cases were family (143), community (97) and schools/preschools
      (87). The number of cases per outbreak ranged from 2 to 11, except one outbreak
      that occurred in 83 young homosexual men with high-risk sexual practices. The
      main factors related to the case index or to coprimary cases included belonging
      to age groups with low immunity (children and young adults) and travelling to or
      from endemic areas. CONCLUSION: Hepatitis A outbreaks in Catalonia are still
      frequent. They mainly occur in the family environment, by person-to-person
      transmission and in the most vulnerable groups (preschool or school employees,
      travelers, and men who perform high-risk sexual practices with other men).

PMID- 16956532
TI  - [Description of an outbreak of Campylobacter jejuni gastroenteritis and molecular
      characterization of the implicated strain].
AB  - INTRODUCTION: The aim of this study is to describe an outbreak of diarrhea caused
      by Campylobacter jejuni in a primary school. METHODS: Stool samples from five
      patients were cultured. Molecular typing of the isolated strains was performed
      using PCR-RFLP-flaA, PFGE and MLST. RESULTS: Campylobacter jejuni was isolated
      from all five patients. Two of the five strains were available for typing. The
      DNA patterns of the two isolates were indistinguishable. CONCLUSION: The results
      suggest that the causal strain had a common identity.

PMID- 16956533
TI  - [Trichinellosis: epidemiological, clinical and laboratory aspects. A
      retrospective study (1994-2003)].
AB  - BACKGROUND: Trichinellosis is a parasitic zoonosis caused by ingestion of
      infected meat containing cysts of Trichinella spp. OBJECTIVES: To analyze the
      epidemiological, clinical and laboratory findings of trichinellosis patients in
      our center and compare the results with those from published series. To analyze
      the relationship between the clinical symptoms and laboratory findings. MATERIALS
      AND METHODS: The clinical records of 127 patients were retrospectively analyzed.
      RESULTS: Epidemiological: 61% were male and mean age was 32 years; 95% were
      associated with other cases. The food implicated was always pork. Clinical: 45%
      presented gastrointestinal symptoms and 98% systemic symptoms. Three patients
      required intensive care unit hospitalization and one died. In 53%, treatment
      consisted of associated antiparasitic and anti-inflammatory drugs. Laboratory:
      59% presented leukocytosis and 72% absolute eosinophilia. Creatine phosphokinase
      was elevated in 62%, lactic dehydrogenase in 56% and glutamic-oxaloacetic
      transaminase (GOT) in 30%. Among 52 patients, 65% had positive serology;
      trichinoscopy of food samples was positive in three outbreaks. The population
      studied had a mean of 5 signs and/or symptoms. The patient group with more than 5
      signs and/or symptoms presented higher white blood cell counts and GOT levels (p
      < 0.05) CONCLUSIONS: Our results were comparable to those of other series;
      however, there was a low rate of complications. An association was found between
      a larger number of signs and symptoms and higher leukocyte counts and GOT levels.
      The relevance of these findings should be assessed in future studies. There is no
      agreement as to the best therapeutic option, a fact reflected in the various
      treatment modalities seen in our study.

PMID- 16956534
TI  - [Reflections on betalactam antibiotics administered by continuous infusion].
AB  - Numerous studies on continuous intravenous infusion of betalactam antibiotics
      have indicated that this could be a useful strategy for treating nosocomial
      infections as well as exacerbations of pulmonary infections in patients with
      cystic fibrosis and episodes of febrile neutropenia. From the pharmacodynamic
      viewpoint, betalactam antibiotics have a time-dependent behavior. Thus, the
      pharmacokinetic/pharmacodynamic index that best correlates with therapeutic
      efficacy appears to be the time during which free antibiotic concentrations
      remain above the minimum inhibitory concentration (MIC) of the infecting
      microorganism. Continuous infusion of betalactams successfully optimizes this
      pharmacokinetic/ pharmacodynamic index. Furthermore, some studies have shown that
      this therapeutic strategy may be favorable economically.

PMID- 16956535
TI  - [Treatment of viral hepatitis (I). Treatment of chronic hepatitis B].
AB  - In the past 25 years remarkable progress has been made in our understanding of
      the natural history of chronic HBV. The infection is now perceived as having
      three consecutive phases: immune tolerance, immune clearance, and inactive
      carrier status, with possible reactivation episodes. Accumulating evidence
      indicates that antiviral therapy can prevent progression of HBV-related liver
      disease, particularly among patients with sustained response. Five agents are now
      approved for therapy of chronic hepatitis B: interferon-alpha (standard and
      pegylated), lamivudine, adefovir and entecavir. All five drugs are effective in
      suppressing HBV DNA levels and improving serum alanineaminotransferase levels and
      hepatic histology, but it is still unclear who should be treated, with which
      agent (or combination of agents), for how long, and what endpoints measure the
      success or failure of treatment. Until a drug therapy results in lasting
      virological remission in most patients after a reasonably short period of
      treatment, individualized treatment decisions will remain key to maximizing
      efficacy, and chronic HBV infection will continue to be treated as a liver
      disease rather than as an infectious disease.

PMID- 16956536
TI  - [Relapsing fever and Staphylococcus aureus bacteriemia].

PMID- 16956537
TI  - [Constitutional syndrome and bicytopenia having an infectious origin].

PMID- 16956538
TI  - [Soft tissue infection in a diabetic patient from a subtropical region].

PMID- 16956539
TI  - [Mumps virus infection in adulthood].

PMID- 16956540
TI  - [Endocarditis due to Mycoplasma hominis].

PMID- 16956541
TI  - [Sudden death by bacterial meningitis and septic shock: contribution of the post
      mortem diagnosis].

PMID- 16956542
TI  - [PER-1 multiresistant Pseudomonas aeruginosa strain in Spain].

PMID- 16956543
TI  - [Pandoraea pulmonicola isolation in patients with cystic fibrosis].

PMID- 16956544
TI  - Hyperacute fulminant fungal peritonitis and ascites in a HIV-infected patient
      with HCV-related, compensated liver cirrhosis. A supportive role for prolonged
      nimesulide self-administration.

PMID- 16956546
TI  - [Toward a new model of residency supervisor].

PMID- 16956545
TI  - [Stenotrophomonas maltophilia bacteremia after endoscopic retrograde
      cholangiopancreatography].

PMID- 16956547
TI  - [Transanal endoscopic microsurgery (TEM). Current situation and future
      expectations].
AB  - Transanal endoscopic microsurgery (TEM) uses specific equipment that allows
      resection of large rectal adenomas and incipient malignancies in the rectal
      ampulla. TEM aims to provide an alternative to conventional abdominal surgery
      (low anterior resection or abdominoperineal amputations), which carries not
      inconsiderable morbidity and mortality. Application of the technique of endoanal
      excision is limited by the height and extension of the lesions. In this review,
      the authors present their own experience with this technique and that described
      in the literature. The protocol for selecting candidates for TEM, their
      preoperative preparation, equipment, characteristics of the surgical technique,
      postoperative complications, and follow-up are described. The collaboration of a
      multidisciplinary team is essential when developing this technique. TEM
      associated morbidity is low and mortality is practically nil. TEM is the
      technique of choice in large rectal adenomas and malignant rectal tumors in
      stages pT1 localized in the rectal ampulla. The frequency of recurrence is
      similar to that in abdominal surgery. The technique does not cause complications
      of urinary or sexual dysfunction and fecal incontinence is minimal. In more
      advances stages of rectal cancer, the results of better patient selection and
      future studies on the possible application of neoadjuvant therapy associated with
      TEM are required.

PMID- 16956548
TI  - [Update on the residency training program in the Specialty of General and
      Digestive Surgery].

PMID- 16956549
TI  - [How are resident physicians evaluated? The residents' computerized activity
      record].
AB  - INTRODUCTION: Because of the developments that have occurred in surgery in the
      last few years, updates are required not only in the content of resident
      physicians' training but also in evaluation of the knowledge acquired. The
      present article aims to present our experience of an integral evaluation model.
      This model is based on evaluation of theoretical knowledge and surgical skills.
      MATERIAL AND METHOD: The training program for resident physicians (medico interno
      residente [MIR]) has four main branches: clinical work, continuing training,
      research (doctorate) and evaluation of the activity performed (computerized
      activity record). This record allows the theoretical knowledge and skills
      acquired to be evaluated at the end of each rotation. Through 6-monthly
      evaluations, each resident's activity can be quantified over time and compared
      with that of other residents. RESULTS: The system was introduced in July 2004.
      Each resident was given his or her own database. All the activities performed
      were then introduced into the database. The results of overall activity and that
      of each resident are presented. CONCLUSIONS: The method used allows residents'
      integral progress to be followed-up and a completely objective evaluation to be
      made at the end of each year and at the end of the residency period. Widespread
      use of this system, or a similar system, would enable comparisons with other
      centers to be made under similar premises. This system could also help to unify
      criteria and identify deviations in training.

PMID- 16956550
TI  - [Minimally invasive esophagectomy].
AB  - INTRODUCTION: Currently, the bases for the treatment of esophageal cancer are
      surgical resection and chemotherapy. Among the various surgical techniques used,
      minimally invasive esophagectomy (MIE) aims to reduce surgical aggression and
      cardiopulmonary complications while maintaining basic oncological principles. We
      present the results of our initial experience with this technique in the
      treatment of esophageal cancer. MATERIAL AND METHOD: Fourteen patients with a
      diagnosis of esophageal cancer were selected to undergo MIE in three stages:
      right thoracoscopy, laparoscopy, and left cervicotomy with cervical
      esophagogastric anastomosis. Histological diagnosis was epidermoid carcinoma (n =
      11) and high grade dysplasia (n = 3), one of which was highly suspicious of
      malignant transformation. After extension studies, preoperative clinical stages
      were as follows: stage 0 (n = 3), stage IIA (n = 10), and stage III (n = 1).
      Seven patients were treated with chemotherapy and neoadjuvant radiotherapy and
      the remainder underwent surgery without prior treatment. RESULTS: The mean
      operating time was 299 minutes (range: 195-425). The conversion rate was 14% (n =
      2). Mortality was 0% and morbidity was 50%, consisting of three major
      complications and four minor complications. No anastomotic dehiscence or wound
      infections were observed. Complete (R0) resections were achieved in 92.8% (n =
      13). Transfusion needs were 1.1 U/patient. The mean number of nodes removed was
      10.2/patient (range: 5-17). The mean length of hospital stay was 21 days (range:
      9-64). Postoperative follow-up ranged from 1 to 17 months. All patients were
      alive and disease-free except for one patient with liver metastases. CONCLUSIONS:
      Although MIE is a demanding technique, we believe that it is technically feasible
      in the treatment of esophageal cancer with acceptable postoperative morbidity and
      mortality. Consequently, it should be considered as an alternative to open
      surgery in selected patients.

PMID- 16956551
TI  - [Detection of neoplastic lesions in cirrhotic patients waiting for liver
      transplantation].
AB  - INTRODUCTION: Hepatocellular carcinoma is a frequent complication of cirrhosis.
      Liver transplantation is a valid therapeutic option for this disease providing
      that certain morphologic selection criteria (Milan criteria) are fulfilled.
      OBJECTIVE: To evaluate the accuracy of pretransplantation imaging examinations in
      the detection and characterization of neoplastic lesions in cirrhotic candidates
      for liver transplantation. PATIENTS AND METHOD: We performed a retrospective
      study of 250 cirrhotic patients who underwent liver transplantation. The
      preoperative radiological diagnosis was compared with the definitive pathological
      diagnosis, allowing the diagnostic sensitivity of the different techniques, as
      well as the degree of agreement between pre- and postoperative tumoral staging,
      to be identified. RESULTS: Analysis of 250 specimens from total hepatectomy
      identified 58 patients with hepatic tumors, with a total of 136 nodules. Fifty
      three patients had hepatocarcinoma, nine of which were found incidentally. There
      were six radiological false positive diagnoses. Sixty-two percent of patients
      with hepatocarcinoma had multiple lesions. The most sensitive technique for the
      diagnosis of tumors smaller than 1 cm was magnetic resonance imaging. Agreement
      between pre- and postoperative staging was found in only 63.6% of cases;
      consequently, 43% of the patients who exceeded the Milan criteria (20% stage T3
      and 23% stage T4a) underwent transplantation. CONCLUSIONS: Currently used imaging
      techniques lead to a substantial proportion of incorrect stagings in terms of the
      size and number of lesions in cirrhotic patients.

PMID- 16956552
TI  - [Chronic inflammatory portal hypertensive enteropathy in the rat].
AB  - INTRODUCTION: Experimental portal hypertensive enteropathy could have an
      inflammatory etiopathogenesis and, if so, it would produce intestinal remodeling.
      The aim of this study was to test this hypothesis. MATERIAL AND METHOD: Male
      Wistar rats with portal hypertension (PHT) produced by partial portal vein
      ligation were divided into four groups: group I (control; n = 9), group II (PHT;
      n = 8) at 3 months after surgery, group III (control; n = 8), and group IV (PHT;
      n = 10) at 1 year after surgery. The density of duodenal goblet cells and ileal
      levels of tumor necrosis factor (TNF)alpha, interleukin (IL)-1beta, and IL-10
      were studied using an ELISA method. RESULTS: At 3 months after surgery, rats with
      PHT showed an increase in the number of goblet cells in the small bowel (103.63
      +/- 14.37 vs 99.42 +/- 19.19/1,000 microm2). This change was associated with an
      increase (p < 0.05) in ileal levels of TNFalpha (0.20 +/- 0.09 vs 0.08 +/- 0.02
      pmol/mg protein), and IL-1beta (0.40 +/- 0.21 vs 0.19 +/- 0.09 pmol/mg protein),
      as well as with a decrease (p < 0.05) in ileal IL-10 levels (0.06 +/- 0.02 vs
      0.12 +/- 0.03 pmol/mg protein). At 1 year after surgery, rats with PHT showed
      hyperplasia of goblet cells in the small bowel (172.79 +/- 40.46 vs 121.76 +/-
      20.74 /1,000 microm2) (p < 0.01), associated with an increase in ileal levels of
      TNFalpha (0.37 +/- 0.18 vs 0.17 +/- 0.08 pmol/mg protein) (p < 0.05), IL-1beta
      (0.28 +/- 0.14 vs 0.205 +/- 0.05 pmol/mg protein), and IL-10 (0.25 +/- 0.14 vs
      0.20 +/- 0.11 pmol/mg protein). CONCLUSIONS: The increase in TNFalpha and IL
      1beta levels and the decrease in IL-10 level in the small bowel in rats with
      chronic prehepatic PHT suggest the existence of an inflammatory process related
      to goblet cell hyperplasia. This inflammation could be responsible for the
      intestinal epithelial remodeling that occurs in the long term in this
      experimental model.

PMID- 16956553
TI  - [Laparoscopic treatment of ventral hernia under spinal anesthesia].
AB  - INTRODUCTION: Laparoscopic surgery is usually performed with the patient under
      general anesthesia. In open surgery, regional anesthesia has been found to have
      fewer adverse effects than general anesthesia. We studied whether spinal
      anesthesia is feasible in laparoscopic ventral hernia repair. PATIENTS AND
      METHOD: Bupivacaine and fentanyl were administered to obtain T2 block; midazolam
      was used for sedation. Patients underwent laparoscopic intraperitoneal hernia
      repair using an ePTFE prosthesis fixed with a double crown technique. An intra
      abdominal pressure of 12 mmHg and low-flow insufflation (1.5 L/minute) were used
      for pneumoperitoneum. RESULTS: Nineteen out of 23 patients underwent laparoscopic
      ventral hernia repair under spinal anesthesia; conversion to open surgery or
      general anesthesia was required in four patients. Additional sedation
      successfully relieved pain in patients with abdominal and shoulder discomfort
      (10.5%). Hypotension occurred in 68% of patients but was easily resolved by fluid
      administration. CONCLUSIONS: Spinal anesthesia is feasible and well tolerated in
      laparoscopic hernia repair. Studies comparing spinal and general anesthesia in
      this field are warranted.

PMID- 16956554
TI  - [Intestinal linitis plastica: late metastasis from gastric signet ring cell
      adenocarcinoma].
AB  - Linitis plastica is a malignant disease that usually occurs in the stomach,
      although it can affect any segment of the alimentary tract. Typically, this
      entity shows slow progression and insidious clinical course. We present the case
      of a patient with a previous diagnosis of signet ring cell cancer of the stomach
      that had been treated with curative intent 12 years before the clinical onset of
      small and large bowel linitis plastica. The diagnosis was obtained as an
      incidental pathological finding after urgent surgery for intestinal obstruction.
      No gastric mass was found. Linitis plastica should be considered in the
      differential diagnosis of patients with symptoms of obstruction after resection
      of a gastric carcinoma, especially if there are macroscopic surgical findings of
      circumferential narrowing. A long interval after diagnosis and treatment of the
      primary disease does not allow malignancy to be ruled out.

PMID- 16956555
TI  - [Perforated duodenal diverticulum].
AB  - Diverticular disease of the duodenum is uncommon. Perforation is the least
      frequent complication. Diagnosis and treatment are not well defined as the
      presentation and symptomatology are nonspecific. Diagnostic delay carries high
      rates of postoperative mortality (30%). Early diagnosis is essential to reduce
      morbidity and mortality. We present the case of a male patient with perforated
      duodenal diverticulum. This case suggests that computed tomography can be highly
      useful in the preoperative diagnosis of this entity. Treatment consisted of
      duodenal exclusion and retroperitoneal drainage.

PMID- 16956556
TI  - [Gastric adenocarcinoma in Zinsser-Cole-Engman syndrome].
AB  - Zinsser-Cole-Engman syndrome is a congenital dyskeratosis that produces cutaneus
      and hematologic alterations and, in 5% of patients, gastrointestinal neoplasms.
      We report the case of a 37-year-old man with this syndrome who was diagnosed with
      gastric adenocarcinoma. This case provides an example of the management that
      should be followed with these patients in order to identify neoplasms at stages
      in which treatment is curative.

PMID- 16956557
TI  - [Image of the month: malignant cystic teratoma].

PMID- 16956558
TI  - [Intraoperative parathyroid hormone determination in the surgery of
      hyperparathyroidism].

PMID- 16956559
TI  - [Carcinoid tumor of the intrahepatic biliary tract].

PMID- 16956560
TI  - [Unicentric Castleman's disease. Utility of laparoscopy in its diagnosis and
      treatment].

PMID- 16956561
TI  - [Epidermal growth factor receptor inhibitors side effects].
AB  - Epidermal growth factor receptor (EGFR) inhibitors are a new group of drugs used
      in the treatment of several malignancies. Three molecules are approved at the
      moment: gefitinib and erlotinib for the treatment of non-small-cell lung cancer,
      and cetuximab for colorectal cancer. These drugs originate cutaneous side effects
      with a high frequency: acneiform rashes, paronychia and generalized xerodermia.
      In this paper we review these common side effects and how to manage them.

PMID- 16956562
TI  - [Treatment of mycosis fungoides with PUVA and bexarotene].
AB  - INTRODUCTION: The combined use of bexarotene and PUVA is a treatment that is
      currently being investigated. In this paper, six patients treated with this
      combination are presented. OBJECTIVES: To assess the efficacy and safety of
      treatment with PUVA + bexarotene in patients with mycosis fungoides (MF).
      Patients, material and methods. Six patients diagnosed with MF in different
      stages, who received three sessions of PUVA treatment a week (initially 2.35 J/cm
      2, with progressive increases to a maximum of 23.5 J/cm 2) + bexarotene (initial
      dose 300 mg/m 2/day, decreasing to 200, 150 or 75 mg/m 2 if signs of toxicity
      appeared). All received atorvastatin. RESULTS: Stage at the start of treatment:
      two patients IIb, one patient Ib with B2 blood involvement, two patients Ib, one
      patient Ia. Five of the six patients responded to the treatment (three full
      remissions [FR], two partial remissions [PR]). One patient did not respond. In
      those in whom FR was achieved, the time required for the response was 10, 20 and
      24 weeks. All presented with hypertriglyceridemia (maximum 1194 mg/ dL). It was
      necessary to administer thyroid hormone supplements to four of the patients. Two
      of them had alterations in the hepatic biochemistry values, and two others
      presented with alterations in the muscle profile analysis. CONCLUSION: The
      combination of PUVA and bexarotene is a safe and effective treatment for MF. It
      will be necessary to await the results of the clinical trials currently underway
      to see if their combined use is better than treatment with PUVA alone. The
      response rate (RR) was 86 % (three FR and two PR out of six patients).

PMID- 16956563
TI  - [Research on sexually transmitted infections in asymptomatic heterosexual males
      whose partners have cervical intraepithelial neoplasia].
AB  - INTRODUCTION: Human papillomaviruses (HPV) are the etiological agents of genital
      warts and of cervical intraepithelial neoplasia (CIN), and they are sexually
      transmitted. The aim of this study is to determine the prevalence of sexually
      transmitted infections (STI) in asymptomatic heterosexual males who consult their
      physicians seeking advice after their partners have been diagnosed with CIN.
      METHODS: 181 asymptomatic males whose partners were women diagnosed with CIN were
      studied at the STI unit in Gijon over a five-year period (1999-2003). The same
      diagnostic protocol was used in all cases: clinical exam, genitoscopy and the
      taking of samples for bacterial, fungus and Trichomonas cultures, as well as
      samples for the genomic detection of Chlamydia, and syphilis, HIV and viral
      hepatitis serology. RESULTS: 101 infections were diagnosed in 85 patients (47 %).
      By order of greatest prevalence, these were: urethritis from Ureaplasma
      urealyticum (35/181; 19.3 %), genital warts (31/181; 17.1 %), Haemophilus spp.
      (12 de 181; 6.6 %) and mycotic balanoposthitis (10/181; 5.5 %). CONCLUSIONS: The
      prevalence of STI in the partners of women with CIN is high, and in these cases
      it is necessary to establish STI detection and control programs in both members
      of the couple.

PMID- 16956564
TI  - [Revival of syphilis in Malaga].
AB  - INTRODUCTION: In our milieu, syphilis has been truly rare in recent years,
      although it has never ceased to be present. However, we would like to draw
      attention to its recent revival, presenting with certain peculiarities. PATIENTS
      ADN METHODS: The characteristics of 12 cases of syphilis diagnosed in our
      dermatology department between June and December 2004 were studied. RESULTS: Only
      one of the 12 patients, whose ages ranged from 20 to 48, was female, and six were
      homosexual. Five of the latter and one heterosexual were also infected with the
      human immunodeficiency virus. Three patients were diagnosed in the primary stage,
      while the other nine showed alterations characteristic of the second stage,
      although five of them were not aware of having had chancres or adenopathies.
      Serology tests were key to the diagnosis, because of the great variety of
      clinical manifestations. All of the patients responded well to penicillin
      treatment. CONCLUSION: Luetic serology should be performed in patients with
      symptoms that suggest secondary syphilis, especially in homosexuals and those who
      are HIV positive.

PMID- 16956565
TI  - [Multiple post-chemotherapy plantar nevi].
AB  - The induction of multiple melanocytic nevi in children after chemotherapy has
      been documented in the literature. This situation apparently has more to do with
      the state of immunosuppression that is produced than with any specific agent
      used. We present the case of a 12-year-old girl who presented with multiple
      plantar melanocytic nevi after multidrug chemotherapy for acute lymphocytic
      leukemia. None of the lesions showed any alarming clinical signs. Although the
      degeneration of post-chemotherapy melanocytic nevi to melanoma has not been
      documented in any of the cases described, the presence of a high number of
      melanocytic nevi is an accepted risk factor for melanoma; thus, close clinical
      follow-up of these patients seems advisable.

PMID- 16956566
TI  - [Generalized pustular psoriasis and cytolytic hepatitis associated with
      neutrophilic cholangitis].
AB  - Generalized pustular psoriasis (GPP) of the von Zumbusch type may be associated
      with liver disorders, usually resulting in cholestatic hepatitis with
      neutrophilic cholangitis. We describe the case of a woman who experienced a first
      episode of GPP, during which she presented with an increase in hepatic cytolysis
      parameters. An abdominal ultrasound and serological studies did not show any
      significant anomalies. A liver biopsy showed the presence of a neutrophilic
      infiltrate around the bile ducts of the portal space. In short, this fact
      suggests that neutrophilic cholangitis in the context of this disease may
      initially show patterns of analytical alterations other than the classically
      described cholestatic pattern.

PMID- 16956567
TI  - [Digital acrometastasis].
AB  - Cutaneous metastases are infrequent and in some cases represent the first
      manifestation of an unknown neoplasm. Acrally located metastases are particularly
      rare, and the prognosis is very poor, with a survival time of only a few months.
      Although the clinical presentation varies, they are generally confused with an
      infectious or inflammatory process, which delays diagnosis. When they are located
      on the fingers, the most frequent cause is lung carcinoma, while those located on
      the toes are usually due to tumors in the genitourinary tract. The histology of
      the metastasis is similar to that of the primary tumor, although less
      differentiated. In most acrometastases, first the bone and then the skin are
      affected. Treatment is palliative. We present the case of a patient with a
      metastasis on the big toe as an initial sign of a previously unknown lung tumor.

PMID- 16956568
TI  - [Analysis of the COL1A1-PDGFB fusion gene in a case of dermatofibrosarcoma
      protuberans with a fibrosarcoma component].
AB  - Dermatofibrosarcoma protuberans (DFSP) is an infrequent tumor of intermediate
      malignancy, with little tendency to develop metastases but with a high rate of
      local recurrence. Cytogenetically, DFSP is characterized by a reciprocal
      translocation, t(17;22)(q22;q13), which is a conditioning factor in the fusion of
      the collagen type I alpha I gene (COL1A1) in chromosome 17q with the platelet
      derived growth factor beta chain gene (PDGFB) in chromosome 22q. The fusion of
      these genes is variable, involving one of the 51 exons of the COL1A1 gene and
      exon 2 of the PDGFB gene. We present the case of a 37-year-old woman with a tumor
      on the arm whose histology showed a neoplastic infiltration of the subcutaneous
      cellular tissue made up of fusiform cells with an elongated nucleus in a
      storiform pattern and other more pleomorphic cells in a herringbone pattern,
      compatible with DFSP with a fibrosarcoma component. The molecular biology study
      with RT-PCR analysis of paraffin-embedded material and later sequencing showed a
      new fusion of exon 19 of the COL1A1 gene and exon 2 of PDGFB, supporting a
      diagnosis of DFSP. A study of the COL1A1-PDGFB fusion products is useful in cases
      where histology and immunohistochemistry are insufficient for the differential
      diagnosis of DFSP versus other sarcomas. It also justifies the use of new avenues
      of treatment with tyrosine kinase inhibitors.

PMID- 16956569
TI  - [Keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK
      syndrome)].
AB  - We describe the case of a 32-year-old male patient who had presented from birth
      with generalized ichthyosiform dermatosis, palmoplantar keratoderma with
      constrictive bands around the fingers and keratotic plaques in a linear
      arrangement, located in the large skin folds. The dermatopathological examination
      showed orthokeratotic hyperkeratosis and epidermal hyperplasia with
      hypergranulosis. No other members of the patient's family were affected. With
      these clinical and histological findings, the diagnosis was keratosis linearis
      with ichthyosis congenita and sclerosing keratoderma (KLICK syndrome). The
      patient rejected treatment with oral retinoids and was treated with emollients
      and 30 % urea creams, with little clinical response.

PMID- 16956570
TI  - [Post-radiotherapy telangiectasias. Treatment with pulsed-dye laser. Sequential
      histological studies].
AB  - Chronic radiodermatitis after radiotherapy is a frequent sequela that may be
      worrying for the patient. Few cases have been published in the literature in
      which pulsed-dye laser has been used in the treatment of telangiectasias that
      appeared after radiotherapy for breast cancer. We present a female patient with
      radiodermatitis on the neck after radiotherapy for nasopharyngeal carcinoma. The
      patient received five sessions of pulsed-dye laser treatment (3 ms pulse
      duration, 7 mm spot size, fluence between 7 and 12 J/cm 2). Sequential
      histological studies were performed. The response to treatment was very good,
      with the lesions almost completely disappearing. The patient was very satisfied
      with the result. Pulsed-dye laser is a safe and effective treatment for chronic
      radiodermatitis of the neck after radiotherapy.

PMID- 16956571
TI  - [Netherton syndrome].
AB  - Netherton syndrome is a rare disease inherited as an autosomal recessive trait
      due to mutations in the SPINK5 gene. It is characterized by the triad of
      ichthyosiform dermatosis, alterations of the hair shaft and immunological
      disorders. We present the case of a 12-year-old girl with the triad of ichthyosis
      linearis circumflexa, trichorrhexis invaginata and atopic dermatitis,
      characteristic of Netherton syndrome.

PMID- 16956572
TI  - [Onychomycosis and balanitis in a 5-year-old boy].

PMID- 16956573
TI  - [Single blister in pretibial region].

PMID- 16956574
TI  - [Surgical pearl: transparent template in Mohs surgery].

PMID- 16956575
TI  - [Type 1 segmental manifestation of multiple glomangiomas].

PMID- 16956576
TI  - Modulation of proton-induced current fluctuations in the human nicotinic
      acetylcholine receptor channel.
AB  - The nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel that
      switches upon activation from a closed state to a full conducting state. We found
      that the mutation delta S268K, located at 12' position of the second
      transmembrane domain of the delta subunit of the human nAChR generates a long
      lived intermediate conducting state, from which openings to a wild-type like
      conductance level occur on a submillisecond time scale. Aiming to understand the
      interplay between structural changes near the 12' position and channel gating, we
      investigated the influence of various parameters: different ligands
      (acetylcholine, choline and epibatidine), ligand concentrations, transmembrane
      voltages and both fetal and adult nAChRs. Since sojourns in the high conductance
      state are not fully resolved in time, spectral noise analysis was used as a
      complement to dwell time analysis to determine the gating rate constants. Open
      channel current fluctuations are described by a two-state Markov model. The
      characteristic time of the process is markedly influenced by the ligand and the
      receptor type, whereas the frequency of openings to the high conductance state
      increases with membrane hyperpolarization. Conductance changes are discussed with
      regard to reversible transfer reaction of single protons at the lysine 12' side
      chain.

PMID- 16956578
TI  - The effects of anxiety upon attention allocation to affective stimuli.
AB  - Pictures of emotionally aversive, neutral, and pleasant scenes were presented for
      500 ms, followed by a probe presented in the same location (valid trials) or an
      alternate location (invalid trials) as the picture. Response-times to the probes
      were recorded in low (N=20) and high (N=27) trait anxious participants. Results
      revealed an overall negative cue validity effect of shorter reaction times (RTs)
      on invalid than valid trials, suggestive of an inhibition of return effect.
      Moreover, high trait anxious females showed a reduced negative cue validity
      effect for aversive pictures in comparison with neutral and pleasant pictures,
      suggestive of selective interference by the unpleasant material. By contrast, low
      trait anxious females showed an enhanced negative cue validity effect for
      aversive pictures relative to neutral and pleasant pictures, suggestive of
      attentional avoidance of the aversive content. The emotional content of picture
      cues did not significantly affect RTs in males, regardless of anxiety status. The
      results suggest that biased attention processes for aversive stimuli may
      contribute to the greater female propensity for anxiety disorders.

PMID- 16956577
TI  - Solvent-dependent structure of two tryptophan-rich antimicrobial peptides and
      their analogs studied by FTIR and CD spectroscopy.
AB  - Structural changes for a series of antimicrobial peptides in various solvents
      were investigated by a combined approach of FTIR and CD spectroscopy. The well
      characterized and potent antimicrobial peptides indolicidin and tritrpticin were
      studied along with several analogs of tritrpticin, including Tritrp1 (amidated
      analog of tritrpticin), Tritrp2 (analog of Tritrp1 with Arg-->Lys substitutions),
      Tritrp3 (analog of Tritrp1 with Pro-->Ala substitutions) and Tritrp4 (analog of
      Tritrp1 with Trp-->Tyr substitutions). All peptides were studied in aqueous
      buffer, ethanol and in the presence of dodecylphosphocholine (DPC) micelles. It
      was shown that tritrpticin and its analogs preferentially adopt turn structures
      in all solvents studied. The turn structures formed by the tritrpticin analogs
      bound to DPC micelles are more compact and more conformationally restricted
      compared to indolicidin. While several peptides showed a slight propensity for an
      alpha-helical conformation in ethanol, this trend was only strong for Tritrp3,
      which also adopted a largely alpha-helical structure with DPC micelles. Tritrp3
      also demonstrated along with Tritrp1 the highest ability to interact with DPC
      micelles, while Tritrp2 and Tritrp4 showed the weakest interaction.

PMID- 16956579
TI  - The human myeloperoxidase gene is regulated by LXR and PPARalpha ligands.
AB  - Myeloperoxidase (MPO) is an oxidant-generating enzyme expressed in macrophages
      and implicated in atherosclerosis and cholesterol homeostasis. LXRalpha and
      PPARalpha regulate genes involved in cholesterol metabolism and the inflammatory
      response in macrophages. Here, we examine the effect of LXR and PPARalpha ligands
      on MPO expression. LXR and PPARalpha, as heterodimers with RXR, are shown to bind
      overlapping sites in an Alu receptor response element (AluRRE) in the MPO
      promoter. The LXR ligand T0901317 suppresses MPO mRNA expression in primary human
      macrophages, and in bone marrow cells and macrophages from huMPO transgenic mice.
      The PPARalpha ligand GW9578 downregulates MPO expression in GMCSF-macrophages,
      while upregulating in MCSF-macrophages. In contrast, the mouse MPO gene, which
      lacks the primate-specific AluRRE, is not regulated by LXR or PPARalpha ligands.
      These findings identify human MPO as a novel LXR and PPARalpha target gene,
      consistent with the role of these receptors in regulation of proinflammatory
      genes in macrophages.

PMID- 16956580
TI  - Akt phosphorylation is essential for nuclear translocation and retention in NGF
      stimulated PC12 cells.
AB  - Nerve growth factor (NGF) elicits Akt translocation into the nucleus, where it
      phosphorylates nuclear targets. Here, we describe that Akt phosphorylation can
      promote the nuclear translocation of Akt and is necessary for its nuclear
      retention. Overexpression of Akt-K179A, T308A, S473A-mutant failed to show either
      nuclear translocation or nuclear Akt phosphorylation, whereas expression of wild
      type counterpart elicited profound Akt phosphorylation and induced nuclear
      translocation under NGF stimulation. Employing the PI3K inhibitor and a variety
      of mutants PI3K, we showed that nuclear translocation of Akt was mediated by
      activation of PI3K, and Akt phosphorylation status in the nucleus required PI3K
      activity. Thus the activity of PI3K might contribute to the nuclear translocation
      of Akt, and that Akt phosphorylation is essential for its nuclear retention under
      NGF stimulation conditions.

PMID- 16956581
TI  - Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats.
AB  - Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation
      of smooth muscle cells (SMCs), leading to occlusion of pulmonary arterioles,
      right ventricular (RV) hypertrophy, and death. We investigated whether
      mycophenolate mofetil (MMF), a potent immunosuppresssant, prevents the
      development of monocrotaline (MCT)-induced PAH in rats. MMF effectively decreased
      RV systolic pressure and RV hypertrophy, and reduced the medial thickness of
      pulmonary arteries. MMF significantly inhibited the number of proliferating cell
      nuclear antigen (PCNA)-positive cells, infiltration of macrophages, and
      expression of P-selectin and interleukin-6 on the endothelium of pulmonary
      arteries. The infiltration of T cells and mast cells was not affected by MMF. In
      vitro experiments revealed that mycophenolic acid (MPA), an active metabolite of
      MMF, dose-dependently inhibited proliferation of human pulmonary arterial SMCs.
      MMF attenuated the development of PAH through its anti-inflammatory and anti
      proliferative properties. These findings provide new insight into the potential
      role of immunosuppressants in the treatment of PAH.

PMID- 16956582
TI  - Extracellular NAD+ metabolism modulates osteoclastogenesis.
AB  - Changes in NAD+ and its metabolites contribute to longevity and age-associated
      diseases. The role of NAD+ metabolism in bone diseases has however not been
      investigated, despite the fact that osteoporosis is a leading cause of morbidity
      in old age. TRAP(+) osteoclast formation from C57 Bl/6J mice was assessed after
      the addition of varying concentrations of NAD+ metabolites or exogenous
      ADPribosyl cyclase and NADase enzymes. The NAD+ metabolite cyclic ADPribose
      (cADPr) or exogenous addition of the enzyme ADPribosyl cyclase stimulated
      osteoclast formation. Blocking cADPr action with the antagonist 8-Br-cADPr
      potently inhibited osteoclast formation. In contrast to cADPr, its noncyclized
      derivative ADPribose (ADPr) or the exogenous addition of NADase both inhibited
      osteoclastogenesis. As CD38 is the major NAD+ -degrading enzyme present in the
      bone marrow, these results suggest that CD38-mediated inhibition of
      osteoclastogenesis is related to its NADase activity, not its ADPribosyl cyclase
      activity.

PMID- 16956583
TI  - Detection of redox-based modification in two-dimensional electrophoresis
      proteomic separations.
AB  - Oxidative stress arises when cellular defenses against molecular oxygen and its
      by-products (reactive oxygen species; ROS) are overcome leading to covalent
      modification of lipids, DNA, and protein. Redox-based modification of proteins
      can be conveniently studied by proteomic analysis using two-dimensional
      electrophoresis (2D SDS-PAGE). Despite some technical shortcomings, this
      technique allows rapid and quantitative analysis of paired samples, the
      visualization of discrete protein spots, and provides a robust platform for
      subsequent analysis and identification of specific proteins. Exposure to
      oxidative stress introduces a wide range of reversible or irreversible
      alterations to amino acid side chains. These include carbonylation,
      glutathionylation, formation of mixed disulphides, effects on disulphide bridge
      patterns, ubiquitinylation, and racemization. Identification of proteins targeted
      for specific modification adds a deeper dimension to the dissection of effects of
      oxidative stress on the proteome with potentially far-reaching implications. This
      article describes key methodologies now available for identification of redox
      based modifications in proteins separated by 2D SDS-PAGE.

PMID- 16956584
TI  - PTP1B-dependent insulin receptor phosphorylation/residency in the endocytic
      recycling compartment of CHO-IR cells.
AB  - Insulin binds to the alpha subunit of the insulin receptor (IR) on the cell
      surface. The insulin-IR complex is subsequently internalized and trafficked
      within the cell. Endocytosed receptors, devoid of insulin, recycle back to the
      plasma membrane through the endocytic recycling compartment (ERC). Using a high
      content screening system, we investigate the intracellular trafficking of the IR
      and its phosphorylation state, within the ERC, in response to protein tyrosine
      phosphatase-1B (PTP1B) inhibition. Insulin stimulates, in a time- and dose
      dependent manner, the accumulation of phosphorylated IR (pY(1158,1162,1163 IR) in
      the ERC of CHO-IR cells. Treatment of CHO-IR cells with PTP1B-specific inhibitors
      or siRNA leads to dose-dependent increases in IR residency and phosphorylation
      within the ERC. The results also demonstrate that PTP1B redistributes within CHO
      IR cells upon insulin challenge. The established system will allow for efficient
      screening of candidate inhibitors for the modulation of PTP1B activity.

PMID- 16956585
TI  - NF-kappaB in solid tumors.
AB  - Cancer is a multistep process during which cells acquire genetic alterations that
      drive the progressive transformation of normal cells into highly malignant cells.
      Self-sufficiency in growth, insensitivity to anti-growth signals, evasion of
      apoptosis, limitless replicative potential, sustained angiogenesis, tissue
      invasion and metastasis, are signatures of transformed cells. NF-kappaB is a key
      actor in tumorigenesis given its ability to control the expression and the
      function of a number of genes involved in these processes. Indeed, constitutive
      activation of NF-kappaB is a common feature of many human tumors, while its
      sustained activation during inflammation predisposes normal cells to neoplastic
      transformation. Since suppression of NF-kappaB has been shown to inhibit
      oncogenic potential of transformed cells, targeting it should be effective in the
      prevention and treatment of cancer.

PMID- 16956586
TI  - The effects of attentional load on auditory ERPs recorded from human cortex.
AB  - Responses to acoustic input were recorded from human temporal cortex using
      subdural electrodes in order to investigate in greater anatomical detail how
      attentional load modulates exogenous auditory responses. Four patient-volunteers
      performed a dichotic listening task in which they listened for rare frequency
      deviants in a series of tones presented to both ears at interstimulus intervals
      (ISIs) of 400, 800, and 2000 ms. Across all ISIs, stimuli presented contralateral
      to electrode location produced the strongest deflections in the averaged ERP at
      approximately 90 and 170 ms post-stimulus on average (labeled N90stg and
      P170stg). Maximal recording sites for these peaks most often occurred over the
      Sylvian fissure or the upper bank of the posterior superior temporal gyrus.
      Neither ISI nor selective attention exhibited substantial effects on peak
      latencies. However, as presentation rates increased (decreasing ISI), overall
      averaged event-related potential (ERP) amplitudes declined significantly, while
      attending to the contralateral stimulus significantly increased both the N90stg
      and P170stg peaks for most patients. This effect of attention increased with
      decreasing ISI for both components most clearly in the difference between the
      grand-average ERPs for attending to vs. ignoring the contralateral stimulus, and
      even more dramatically in the percentage ratio of that difference over the mean
      peak amplitude. This amplifying effect of attention with increasing load, along
      with its anatomical location, suggests that attention can enhance exogenous
      sources in auditory cortex.

PMID- 16956587
TI  - Absence of the basilar pons in mice lacking a functional Large
      glycosyltransferase gene suggests a defect in pontine neuron migration.
AB  - Several forms of congenital muscular dystrophy result from mutations in
      glycosyltransferases that modify alpha-dystroglycan. As pontine hypoplasia has
      been reported in some clinical cases of congenital muscular dystrophy, we have
      begun to examine whether these glycosyltransferases are required for the normal
      development of the basilar pons, one of several precerebellar nuclei of the
      hindbrain. In veils (Large(vls)) mice, which carry a loss-of-function mutation in
      the Large glycosyltransferase gene, the basilar pons is absent. Instead, ectopic
      clusters of pontine neurons are found lateral to their normal site, suggesting
      that these neurons are unable to migrate to their appropriate site. Two other
      precerebellar nuclei, the lateral reticular nucleus and the inferior olive, are
      present in Large(vls) mice. In addition, the basilar pons forms normally in
      dystrophin-deficient mice. These results demonstrate that the Large
      glycosyltransferase but not dystrophin is required for normal basilar pontine
      development.

PMID- 16956588
TI  - Leptin and thyrotropin-releasing hormone: cooperative action in the hindbrain to
      activate brown adipose thermogenesis.
AB  - Explanations of leptin induction of thermogenesis typically involve primary
      detection elements in the hypothalamus. In turn, these circuits control medullary
      raphe neurons that regulate spinal efferent sympathetic projections to heat
      producing brown adipose tissue (BAT). The hindbrain may be capable of
      considerable thermoregulatory capacity independent of the hypothalamus, though
      little is known about the site(s), mechanism(s) of action, or the physiological
      consequences of leptin action in the hindbrain. Several reports describe the
      presence of leptin receptor in the solitary nucleus, and there is functional
      evidence that leptin can act in the dorsal medulla to suppress feeding. We
      examined the effects of leptin, applied to the dorsal medulla, on BAT
      thermogenesis. Leptin alone (< or =25 microg) had no independent effect on BAT
      thermogenesis. We hypothesized that, while leptin may not be capable of
      activating thermocontrol mechanisms in the hindbrain directly, it may modulate
      the efficacy of other neural signals involved in the control of thermogenesis
      such as thyrotropin-releasing hormone (TRH). We tested the hypothesis that leptin
      and TRH, acting in the hindbrain, co-regulate thermogenesis. As expected, TRH
      (0.1 microg), alone, produces a small increase (+0.75 degrees C) in BAT
      temperature. Co-application of leptin (5 mug) and TRH (0.1 microg) to the dorsal
      medulla produces an increase in BAT and core temperature more than 300% greater
      than TRH alone (+3.5 degrees C). This effect is undiminished in the acute
      decerebrate rat, suggesting that the effect is mediated entirely by the
      hindbrain.

PMID- 16956590
TI  - Mapping sentence form onto meaning: the syntax-semantic interface.
AB  - The understanding of sentences involves not only the retrieval of the meaning of
      single words, but the identification of the relation between a verb and its
      arguments. The way the brain manages to process word meaning and syntactic
      relations during language comprehension on-line still is a matter of debate. Here
      we review the different views discussed in the literature and report data from
      crucial experiments investigating the temporal and neurotopological parameters of
      different information types encoded in verbs, i.e. word category information, the
      verb's argument structure information, the verb's selectional restriction and the
      morphosyntactic information encoded in the verb's inflection. The
      neurophysiological indices of the processes dealing with these different
      information types suggest an initial independence of the processing of word
      category information from other information types as the basis of local phrase
      structure building, and a later processing stage during which different
      information types interact. The relative ordering of the subprocesses appears to
      be universal, whereas the absolute timing of when during later phrases
      interaction takes places varies as a function of when the relevant information
      becomes available. Moreover, the neurophysiological indices for non-local
      dependency relations vary as a function of the morphological richness of the
      language.

PMID- 16956589
TI  - The role of TNF-alpha and its receptors in the production of NGF and GDNF by
      astrocytes.
AB  - The neurotrophic factors, nerve growth factor (NGF) and glial cell line-derived
      neurotrophic factor (GDNF), are produced by astrocytes, and are induced by
      inflammatory stimuli including bacterial lipopolysaccharide and pro-inflammatory
      cytokines. In this study, we examined the regulatory mechanisms of tumor necrosis
      factor-alpha (TNF-alpha)-induced production of neurotrophic factors. We show here
      that cultured astrocytes express both TNF-alpha receptor 1 (TNFR1) and TNFR2, and
      that activation of these receptors by TNF-alpha promotes expression of both NGF
      and GDNF. In addition, we observe that not only exogenous TNF-alpha but also TNF
      alpha produced by astrocytes induce NGF and GDNF production in astrocytes. These
      results suggest that an autocrine loop involving TNF-alpha contributes to the
      production of neurotrophic factors in response to inflammation.

PMID- 16956591
TI  - Ebselen effects on MPTP-induced neurotoxicity.
AB  - We evaluated the effect of ebselen on human SH-SY5Y dopaminergic neuronal cells
      and determined whether ebselen, a glutathione peroxidase-mimetic, protected
      against MPTP-induced dopamine depletion in mice. Ebselen (10-100 microM)
      inhibited the proliferation of SH-SY5Y cells dose-dependently. Ebselen did not
      induce any behavioral changes and did not block MPTP-induced tremor and akinesia.
      Ebselen had no effect on the monoamine oxidase activity and did not protect
      against MPTP-induced dopamine depletion in striatum.

PMID- 16956592
TI  - Differential effects of antidepressants on dexamethasone-induced nuclear
      translocation and expression of glucocorticoid receptor.
AB  - The glucocorticoid receptor (GR) is a key regulator of the hypothalamic-pituitary
      adrenal (HPA) axis. Mood disorder patients often exhibit abnormalities in this
      axis. Although the clinical benefit of antidepressants is associated with the
      normalization of the disturbed HPA activity by enhanced negative feedback of the
      HPA axis, the precise mechanism remains unknown. In order to examine the effect
      of antidepressants on the translocation of GR into the nucleus, we performed time
      lapse observation on SY5Y cells that had been transiently transfected with
      plasmids expressing the green fluorescence protein (GFP)-tagged GRalpha.
      Clomipramine and desipramine facilitated dexamethasone (Dex)-induced GFP-GRalpha
      nuclear translocation. Coincubation of verapamil, an inhibitor of membrane
      steroid transporters, showed little or no additive effect on GFP-GRalpha nuclear
      translocation induced by both Dex and clomipramine. In the absence of Dex,
      antidepressants did not induce the translocation of GFP-GRalpha into the nucleus.
      Using real-time PCR, we examined the effect of antidepressants on splicing
      isoform of GR, GRalpha, and GRbeta in SY5Y and Jurkat cells. Incubation with
      paroxetine and desipramine for 48 h and 7 days increased GRalpha expression,
      whereas the expression of GRbeta remained stable. Antidepressants did not alter
      the expression of SRp30c that is associated with alternative splicing of GR
      transcript. Thus, antidepressants exert differential effects on the translocation
      and expression of GR to enhance GR signaling.

PMID- 16956593
TI  - Association between the functional polymorphism in the matrix metalloproteinase-7
      promoter and susceptibility to adult astrocytoma.
AB  - To study the association between the A to G transition at the -181-bp position in
      the promoter of matrix metalloproteinase-7 gene (MMP-7-181A/G) and susceptibility
      to adult astrocytoma, the MMP-7-181A/G polymorphism was genotyped by PCR-RFLP
      analysis among 221 adult astrocytoma patients and 366 healthy controls in a
      population of northern China. The result showed that the overall distribution of
      the MMP-7 genotypes among astrocytoma patients and healthy controls was
      significantly different (P<0.001). Compared with the A/A genotype, the G/G
      genotype significantly increased the risk to the development of astrocytoma (age
      and gender adjusted OR=2.77, 95% CI=1.27-6.02), while the MMP-7 A/G genotype only
      marginally increased the risk of developing this cancer (age and gender adjusted
      OR=1.66, 95% CI=0.99-2.84). Stratification analysis showed that the G/G genotype
      significantly increased the risk of astrocytoma only among male subjects (age
      adjusted OR=3.24, 95% CI=1.12-9.41) and individuals younger than 45 years (age
      and gender adjusted OR=3.16, 95% CI=1.09-9.16). When stratified by histological
      grades, a significant higher risk for developing grade II astrocytoma was
      observed among individuals harboring the A/G genotype (age and gender adjusted
      OR=2.06, 95% CI=1.05-4.05), while an about 3-fold elevation of risk to develop
      grades II, III, and IV astrocytomas was observed among individuals with the G/G
      genotype. The present result, for the first time, suggested that the MMP-7-181A/G
      polymorphism might be associated with the susceptibility to adult astrocytoma.

PMID- 16956594
TI  - Individual differences and contextual bias in pronoun resolution: evidence from
      ERPs.
AB  - Although we usually have no trouble finding the right antecedent for a pronoun,
      the co-reference relations between pronouns and antecedents in everyday language
      are often 'formally' ambiguous. But a pronoun is only really ambiguous if a
      reader or listener indeed perceives it to be ambiguous. Whether this is the case
      may depend on at least two factors: the language processing skills of an
      individual reader, and the contextual bias towards one particular referential
      interpretation. In the current study, we used event related brain potentials
      (ERPs) to explore how both these factors affect the resolution of referentially
      ambiguous pronouns. We compared ERPs elicited by formally ambiguous and non
      ambiguous pronouns that were embedded in simple sentences (e.g., "Jennifer Lopez
      told Madonna that she had too much money."). Individual differences in language
      processing skills were assessed with the Reading Span task, while the contextual
      bias of each sentence (up to the critical pronoun) had been assessed in a
      referential cloze pretest. In line with earlier research, ambiguous pronouns
      elicited a sustained, frontal negative shift relative to non-ambiguous pronouns
      at the group-level. The size of this effect was correlated with Reading Span
      score, as well as with contextual bias. These results suggest that whether a
      reader perceives a formally ambiguous pronoun to be ambiguous is subtly co
      determined by both individual language processing skills and contextual bias.

PMID- 16956596
TI  - Effect of delta-aminolevulinic acid and vitamin E treatments on the N-methyl-D
      aspartate receptor at different ages in the striatum of rat brain.
AB  - We report the effects of the chronic treatments with the oxidant agent delta
      aminolevulinic acid (ALA) and with the antioxidant vitamin E on the N-methyl-D
      aspartate (NMDA) receptors in the striatum of 4-, 12- and 24-month-old male
      Wistar rats. ALA and vitamin E were administered daily for 15 days (40 mg/kg i.p.
      and 20 mg/kg i.p. respectively). NMDA receptors were labeled by membrane
      homogenate binding, using tritiated dizocilpine ([3H]MK-801). [3H]MK-801 binding
      in the striatum was significantly decreased at all ages in ALA-treated rats with
      respect to their controls, and in contrast, was significantly increased at all
      ages when rats received the treatment with vitamin E. Western blot assays were
      performed using antibodies against the NR2A subunit, a NMDA receptor subunit
      widely distributed in the brain. We did not find significant differences in the
      amounts of NR2A in rats treated with either ALA or vitamin E with respect to
      those rats not treated. We conclude that the NMDA receptor densities in the rat
      striatum are modified by the chronic treatment with oxidants and antioxidants in
      an age-independent way, at least until 24 months. Also, our results support the
      notion that NR2A is not involved in these modifications.

PMID- 16956595
TI  - The role of peripheral and central sodium channels in mediating brain temperature
      fluctuations induced by intravenous cocaine.
AB  - While cocaine's interaction with the dopamine (DA) transporter and subsequent
      increase in DA transmission are usually considered key factors responsible for
      its locomotor stimulatory and reinforcing properties, many centrally mediated
      physiological and psychoemotional effects of cocaine are resistant to DA receptor
      blockade, suggesting the importance of other non-DA mechanisms. To explore the
      role of cocaine's interaction with Na+ channels, rats were used to compare
      locomotor stimulatory and temperature (NAcc, temporal muscle and skin) effects of
      repeated iv injections of cocaine (1 mg/kg) with those induced by procaine (PRO 5
      mg/kg), a short-acting local anesthetic with negligible effect on the DA
      transporter, and cocaine methiodide (COC-MET 1.31 mg/kg), a quaternary cocaine
      derivative that is unable to cross the blood-brain barrier. While PRO, unlike
      cocaine, did not induce locomotor activation, it mimicked cocaine in its ability
      to increase brain temperature following the initial injection and to induce
      biphasic, down-up fluctuations following repeated injections. This similarity
      suggests that both these effects of cocaine may be driven by its action on Na+
      channels, a common action of both drugs. While COC-MET also did not affect
      locomotor activity, it shared with cocaine and PRO their ability to increase
      brain temperature but failed to induce temperature decreases after repeated
      injections. These findings point toward activation of peripheral Na+ channels as
      the primary mechanism of rapid excitatory effects of cocaine and inhibition of
      centrally located Na+ channels as the primary mechanism for transient inhibitory
      effects of cocaine. DA receptor blockade (SCH23390+eticlopride) fully eliminated
      locomotor stimulatory and temperature-increasing effects of cocaine, but its
      temperature-decreasing effects remained intact. Surprisingly, DA receptor
      blockade also altered the temperature fluctuations caused by PRO and COC-MET,
      suggesting that some of the central effects triggered via Na+ channels are in
      fact DA-dependent. Finally, repeated administration of PRO to animals that had
      previous cocaine experience led to conditioned locomotion and potentiated
      temperature-increasing effects of this drug. It appears, therefore, that, in
      addition to the central effects of cocaine mediated via interaction with the DA
      transporter and potentiation of DA uptake, interaction with peripheral and
      central Na+ channels is important for the initial physiological and, perhaps,
      affective effects of cocaine, likely contributing to the unique abuse potential
      of this drug.

PMID- 16956597
TI  - Zinc release in the lateral nucleus of the amygdala by stimulation of the
      entorhinal cortex.
AB  - Zinc release in the lateral nucleus of the amygdala was examined using rat brain
      slices. The lateral and basolateral nuclei in the amygdala were evidently stained
      by Timm's sulfide-silver staining method. When the amygdala including both the
      nuclei was stimulated with 100 mM KCl by means of in vivo microdialysis,
      extracellular zinc concentration was increased significantly. Zinc release in the
      lateral nucleus of the amygdala innervated by the entorhinal cortex was next
      examined in brain slices double-stained with zinc and calcium indicators.
      Extracellular zinc signal (ZnAF-2) in the lateral nucleus was increased with
      intracellular calcium signal (calcium orange) during delivery of tetanic stimuli
      to the entorhinal cortex. Both the increases were completely inhibited by
      addition of 1 micro M tetrodotoxin, a sodium channel blocker. Furthermore,
      calcium signal in the lateral nucleus during delivery of tetanic stimuli to the
      entorhinal cortex was increased in the presence of 10 micro M CNQX, an AMPA/KA
      receptor antagonist, and this increase was facilitated by addition of 1 mM
      CaEDTA, a membrane-impermeable zinc chelator. The present study suggested that
      zinc is released in the lateral nucleus of the amygdala by depolarization of the
      entorhinal neurons. In the lateral nucleus, zinc released may suppress the
      increase in presynaptic calcium signal.

PMID- 16956598
TI  - In vivo monitoring of extracellular glutamate in the brain with a microsensor.
AB  - Recent discoveries have revealed that glutamatergic neurotransmission in the
      central nervous system is mediated by a dynamic interplay between neurons and
      astrocytes. To enhance our understanding of this process, the study of
      extracellular glutamate is crucial. At present, microdialysis is the most
      frequently used analytical technique to monitor extracellular glutamate levels
      directly in the brain. However, the neuronal and physiological origin of the
      detected glutamate levels is questioned as they do not fulfil the classical
      release criteria for exocytotic release, such as calcium dependency or response
      to the sodium channel blocker tetrodotoxine (TTX). It is hypothesized that an
      analytical technique with a higher spatial and temporal resolution is required.
      Glutamate microsensors provide a promising analytical solution to meet this
      requirement. In the present study, we applied a 10 micro m diameter hydrogel
      coated glutamate microsensor to monitor extracellular glutamate levels in the
      striatum of anesthetized rats. To explore the potential of the microsensor,
      different pharmacological agents were injected in the vicinity of the sensor at
      an approximate distance of 100 micro m. It was observed that KCl, exogenous
      glutamate, kainate and the reuptake inhibitor DL-threo-beta-benzyloxyaspartate
      (DL-TBOA) increased the extracellular glutamate levels significantly. TTX
      decreased the basal extracellular glutamate levels approximately 90%, which
      indicates that the microsensor is capable of detecting neuronally derived
      glutamate. This is one of the first studies in which a microsensor is applied in
      vivo on a routine base, and it is concluded that microsensor research can
      contribute significantly to improve our understanding of the physiology of
      glutamatergic neurotransmission in the brain.

PMID- 16956599
TI  - Progressive increase in conduction velocity across human mesenchymal stem cells
      is mediated by enhanced electrical coupling.
AB  - OBJECTIVE: The purpose of the study was to investigate the development of
      electrical transmission across human adult bone marrow-derived mesenchymal stem
      cells (hMSCs) during long-term co-incubation with cardiomyocytes (CMCs). METHODS:
      Neonatal rat CMCs were cultured in multi-electrode array dishes. A conduction
      block was induced by creating a central acellular channel, yielding two
      asynchronously beating CMC fields. Enhanced green fluorescent protein (eGFP)
      labeled hMSCs from ischemic heart disease patients (n=8), eGFP-labeled hMSCs
      having RNA interference-mediated connexin43 (Cx43) knockdown (n=6), 1,1'
      dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (Dil)-labeled CMCs (n=6), or no
      cells (n=9) were seeded in the channel. Assessment of conduction velocity (CV),
      Cx expression and localization, gap junctional coupling, and intracellular
      electrical recordings were performed for up to 14 days. RESULTS:
      Resynchronization of the two CMC fields occurred within 24 h after seeding of
      hMSCs. CV across hMSCs increased from 1.4+/-0.4 cm/s at day 7 to 3.5+/-0.1 cm/s
      (p<0.05) at day 14. CV across seeded CMCs was 16.8+/-0.2 cm/s throughout this
      period. No resynchronization occurred in the absence of seeded cells. Knockdown
      of Cx43 in hMSCs abolished conduction across the channel completely. Time
      dependent increase of CV across hMSCs was associated with increased Cx43 mRNA and
      protein expression resulting in increased gap junctional coupling. Intracellular
      recordings in coupled hMSCs showed increased conducted action potential (AP)
      amplitude, lower resting membrane potential, and decreased duration of conducted
      AP (p<0.05, day 14 versus day 1). CONCLUSIONS: CV across hMSCs increases
      progressively after 7 days of co-incubation with CMCs, most likely via improved
      electrotonic interaction. This is associated with increased Cx43 expression,
      increased functional gap junctional coupling, and enhanced intercellular
      electrical coupling between hMSCs and CMCs.

PMID- 16956600
TI  - Atherogenic and inflammatory profile of human arterial endothelial cells (HUAEC)
      in response to LDL subfractions.
AB  - BACKGROUND: Electronegative LDL (LDL(-)) is a minor modified LDL fraction present
      in plasma that has been demonstrated to be inflammatory in endothelial cells
      isolated from human umbilical vein (HUVEC). METHODS: A protein array able to
      measure 42 cytokines, chemokines and related compounds involved in atherogenesis
      was used to determine their release into the culture medium of human arterial
      endothelial cells (HUAEC) activated or not by two low-density lipoprotein (LDL)
      fractions isolated from human plasma by anion-exchange chromatography. RESULTS:
      The results of the protein array (confirmed using specific ELISAs for each
      induced factor) revealed that HUAEC in the absence of stimuli released small
      amounts of interleukin 8 (IL-8), monocyte chemotactic protein 1 (MCP-1) and
      growth-related oncogene (GRO). The major native LDL fraction (named LDL(+))
      increased the release of these molecules and also those of interleukin 6 (IL-6)
      and GROalpha. Compared to LDL(+), the minor modified fraction, named
      electronegative LDL (LDL(-)), increased all these factors to a greater degree and
      also induced the release of granulocyte-monocyte colony-stimulating factor (GM
      CSF) and platelet-derived growth factor B (PDGF-B). These results were confirmed
      by ELISA. CONCLUSIONS: All these results indicate that, compared to LDL(+), LDL(
      ) fraction promotes not only the release of proinflammatory factors but also
      those of atherogenic factors in endothelial cells of arterial origin, thereby
      suggesting a new role for LDL(-) in atherogenesis.

PMID- 16956601
TI  - Molecular mechanisms of insulin resistance and associated diseases.
AB  - Insulin resistance is a state in which higher than normal concentrations of
      insulin are required for normal response. The most common underlying cause is
      central obesity, although primary insulin resistance in normal-weight individuals
      is also possible. Excess abdominal adipose tissue has been shown to release
      increased amounts of free fatty acids which directly affect insulin signalling,
      diminish glucose uptake in muscle, drive exaggerated triglyceride synthesis and
      induce gluconeogenesis in the liver. Other factors presumed to play the role in
      insulin resistance are tumour necrosis factor alpha, adiponectin, leptin, IL-6
      and some other adipokines. Hyperinsulinaemia which accompanies insulin resistance
      may be implicated in the development of many pathological states, such as
      hypertension and hyperandrogenaemia. Insulin resistance underlies metabolic
      syndrome and is further associated with polycystic ovary syndrome and
      lipodystrophies. When beta-cells fail to secrete the excess insulin needed,
      diabetes mellitus type 2 emerges, which is, besides coronary heart disease, the
      main complication of insulin resistance and associated diseases.

PMID- 16956602
TI  - Relationship between glomerular filtration rate and the adipokines adiponectin,
      resistin and leptin in coronary patients with predominantly normal or mildly
      impaired renal function.
AB  - BACKGROUND: Due to their molecular weight, it is possible that the adipokines
      adiponectin, resistin and leptin accumulate when glomerular filtration rate (GFR)
      is decreased. In reduced renal clearance, altered serum concentrations of these
      proteins might affect cardiovascular risk. The objective of the study was to
      investigate the relationship between adipokine concentrations and GFR. METHODS:
      The association between GFR, as determined by the abbreviated MDRD equation, and
      the concentrations of the adipokines adiponectin, resistin and leptin was
      assessed in a cohort of coronary patients (n=538; 363 male, 165 female). After
      calculation of correlations between GFR and adipokine concentrations, the
      association was further assessed by analysis of covariance following adjustment
      for age, gender, BMI, presence of type 2 diabetes, presence of hypertension,
      history of smoking as well as for serum lipid concentrations. RESULTS: Mean GFR
      in our study population was 68.74+/-15.27 ml/min/1.73 m(2). 74.3% of the patients
      had a GFR >60 ml/min/1.73 m(2), 24% of the patients had a GFR between 30 and 60
      ml/min/1.73 m(2), and 1.7% of the patients had a GFR <30 ml/min/1.73 m(2). There
      were significant inverse correlations between adiponectin (r=-0.372; p<0.001),
      resistin (r=-0.227; p<0.001) and leptin (r=-0.151; p=0.009) concentrations and
      GFR. After multivariate adjustment, the associations remained significant for
      adiponectin and resistin. Subgroup analysis in patients with GFR >60 ml/min/1.73
      m(2) showed a significant correlation between GFR and adiponectin as well as
      leptin concentrations. However, after adjustment, these associations no longer
      were significant. CONCLUSIONS: There is an independent association between GFR
      and the serum concentrations of adiponectin and resistin. However, this
      association is not present at GFR >60 ml/min/1.73 m(2). This finding suggests
      that adipokine concentrations in mildly impaired and normal renal function are
      influenced by factors other than GFR.

PMID- 16956603
TI  - Fibroblast growth factor 10 is required for survival and proliferation but not
      differentiation of intestinal epithelial progenitor cells during murine colon
      development.
AB  - Epithelial-mesenchymal interactions that govern the development of the colon from
      the primitive gastrointestinal tract are still unclear. In this study, we
      determine the temporal-spatial expression pattern of Fibroblast growth factor 10
      (Fgf10), a key developmental gene, in the colon at different developmental
      stages. We found that Fgf10 is expressed in the mesenchyme of the distal colon,
      while its main receptor Fgfr2-IIIb is expressed throughout the entire intestinal
      epithelium. We demonstrate that Fgf10 inactivation leads to decreased
      proliferation and increased cell apoptosis in the colonic epithelium at E10.5,
      therefore resulting in distal colonic atresia. Using newly described Fgf10
      hypomorphic mice, we show that high levels of FGF10 are dispensable for the
      differentiation of the colonic epithelium. Our work unravels for the first time
      the pivotal role of FGF10 in the survival and proliferation of the colonic
      epithelium, biological activities which are essential for colonic crypt
      formation.

PMID- 16956604
TI  - Activation of adenosine A1 receptor modulates dopamine D1 receptor activity in
      stably cotransfected human embryonic kidney 293 cells.
AB  - The antagonistic interactions between adenosine A1 receptors and dopamine D1
      receptors were studied in a human embryonic kidney 293 cell line stably
      cotransfected with human adenosine A1 receptor and dopamine D1 receptor cDNAs. In
      the cotransfected cells, but not in control cells only transfected with dopamine
      D1 receptors, adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA, 10
      microM) increased the Kd of dopamine D1 receptor antagonist [N-methyl-3H]R(+)-7
      Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine
      ([3H]SCH23390) without affecting the Bmax. Moreover, CPA induced a concentration
      dependent decrease in the affinity of dopamine D1 receptors for the agonist (+/-)
      1-Phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride (SKF38393)
      and inhibited dopamine D1 receptor-mediated cyclic AMP response element
      recruitment. Furthermore, pertussis toxin treatment completely counteracted the
      effects of low concentrations of CPA but only partially counteracted the effects
      of high concentrations of CPA. These results suggest that adenosine A1 receptors
      antagonistically modulate dopamine D1 receptors at the level of receptor binding
      and the second messenger generation. Furthermore, the antagonistic interactions
      between these two receptors induced by low concentrations of CPA might have a
      different manner with those induced by high concentrations of CPA.

PMID- 16956605
TI  - Effects of ciclamilast, a new PDE 4 PDE4 inhibitor, on airway
      hyperresponsiveness, PDE4D expression and airway inflammation in a murine model
      of asthma.
AB  - PDE4 (phosphodiesterase-4) plays a critical role in pathogenesis of allergic
      asthma and chronic obstructive pulmonary disease (COPD). PDE4 inhibitors are
      presently under clinical development for the treatment of asthma and/or COPD.
      Ciclamilast, a new PDE4 inhibitor, is a piclamilast (RP 73401) structural
      analogue, but has a more potent inhibitory effect on PDE4 and inflammation in the
      airway tissues and less side effects than that of piclamilast. In this study, we
      elucidate primarily on the roles of compound on PDE4 enzyme in physiological and
      pathological processes in a mouse model of asthma. The sensitized/challenged mice
      were reexposed to ovalbumin and airway response to inhaled methacholine was
      monitored. Orally administration of ciclamilast, in a dose-dependent manner,
      significantly inhibited changes in lung resistance and lung dynamic compliance,
      as well as upregulation of cAMP-PDE activity, increase of PDE4D mRNA expression,
      but not PDE4B from lung tissue in the murine model. In addition, the compound
      dose-dependently reduced mRNA expression of eotaxin, tumor necrosis factor (TNF)
      alpha and interleukin (IL)-4, but slightly increased mRNA expression of
      interferon (IFN)-gamma from lung tissue. Further, levels of eotaxin, TNF-alpha
      and IL-4, and eosinophil and neutrophil accumulation in bronchoalveolar lavage
      fluid were also significantly reduced. Pathological examination, goblet cell
      hyperplasia and inflammatory cells infiltration in lung tissue were suppressed by
      treatment with ciclamilast. A significant correlation was observed between the
      increases in PDE4D mRNA expression and airway hyperresponsiveness. These studies
      confirm that inhibitory effect of ciclamilast on airway hyperresponsiveness
      includes its inhibiting PDE4D mRNA expression, down-modulating PDE4 activity,
      anti-inflammation and anti-mucus hypersecretion, and ciclamilast may have
      therapeutic potential for the treatment of asthma.

PMID- 16956606
TI  - Zyxin is upregulated in the nucleus by thymosin beta4 in SiHa cells.
AB  - Thymosin beta4 is a 43-amino acid actin-binding protein that promotes cell
      migration and is important in angiogenesis, wound healing, and tumor metastasis.
      We searched for genes upregulated by thymosin beta4 and identified zyxin as
      increased in SiHa cells in the presence of exogenously added thymosin beta4 and
      when thymosin beta4 is overexpressed using adenoviral vectors. Both zyxin and
      thymosin beta4 show increased localization in the nucleus. We conclude that
      thymosin beta4 may exert some of its migration promoting activity via increased
      zyxin expression.

PMID- 16956607
TI  - Inhibition of calpain-mediated cell death by a novel peptide inhibitor.
AB  - Calpains are calcium- and thiol-dependent proteases whose overactivation and
      degradation of various substrates have been implicated in a number of diseases
      and conditions such as cardiovascular dysfunction and ischemic stroke. With
      increasing evidence for calpain's role in cellular damage, the development of
      calpain inhibitors continues to be an important objective. Previously, we
      identified a highly specific calcium-dependent, calpain interacting peptide L-S-E
      A-L, that showed homology to domains A and C of the only known endogenous
      inhibitor of calpains, calpastatin. This suggested that LSEAL had a calpain
      inhibitory function and synthetic LSEAL inhibited calpain I and II proteolysis of
      two calpain substrates, tau and alpha-synuclein. In the present study, we
      demonstrate that synthetic LSEAL is membrane permeable and is a potent inhibitor
      in two established models of calpain-mediated cell death using primary rat
      cortical neurons and SH-SY5Y neuroblastoma cells. In addition, we show that LSEAL
      inhibits calpain activity towards protein substrates as detected by an antibody
      to a calpain-specific breakdown product of spectrin. Taken together, these
      results suggest that LSEAL may represent a novel calpastatin mimetic with the
      potential for benefit in conditions of increased calpain activity such as stroke,
      traumatic brain injury or heart attack.

PMID- 16956608
TI  - Brain metabolism and extracellular space diffusion parameters during and after
      transient global hypoxia in the rat cortex.
AB  - Hypoxia results in both reversible and irreversible changes in the brain
      extracellular space (ECS). This study utilized microdialysis to monitor changes
      in the energy-related metabolites lactate, pyruvate, glucose and glutamate in the
      rat cortex before, during and after 30-min transient global hypoxia, induced in
      anesthetized rats by reducing inspired oxygen to 6% O(2) in nitrogen. Changes in
      metabolite levels were compared with ECS diffusion parameters calculated from
      diffusion curves of tetramethylammonium applied by iontophoresis. Significant
      increases in lactate concentration and the lactate/pyruvate ratio, as well as
      decreased glucose levels, were found in the cortex immediately after the
      induction of hypoxia. Following recovery to ventilation with air, extracellular
      lactate and glucose levels and the lactate/pyruvate ratio returned to control
      levels within 40, 20 and 30 min, respectively. Glutamate levels started to
      increase 20-30 min after the onset of hypoxia and returned to prehypoxic values
      within 30-40 min of reoxygenation. The ECS volume fraction alpha decreased by
      about 5% from 0.18+/-0.01 during the first 20-25 min of hypoxia; after 25 min
      alpha dropped a further 22% to 0.14+/-0.01. Within 10 min of reoxygenation, alpha
      returned to control values, then increased to 0.20+/-0.01 and remained at this
      level until the end of the experiment. The observed 22% decrease in alpha
      markedly influences dialysate levels measured during hypoxia. In our study, the
      complete posthypoxic recovery of cortical metabolite levels and ECS diffusion
      properties suggests that metabolic enzymes and related cellular components (e.g.,
      mitochondria) may tolerate prolonged hypoxic periods and recover to prehypoxic
      values.

PMID- 16956609
TI  - Activation of diacylglycerol O-acyltransferase 1 gene results in increased tumor
      necrosis factor-alpha gene expression in 3T3-L1 adipocytes.
AB  - The tumor necrosis factor-alpha (TNF-alpha) expression has been reported to be
      largely dependent on the size of adipocytes. We herein investigated the gene
      regulation of diacylglycerol O-acyltransferase (DGAT) in order to clarify the
      mechanism of TNF-alpha expression induced in large adipocytes. 3T3-L1 cells were
      cultured in the presence of 5 mM or 25 mM glucose to generate adipocytes from
      which the triglyceride content differs. The expression of TNF-alpha, DGAT1, and
      DGAT2 were upregulated in adipocytes cultured with 25 mM glucose. Furthermore,
      knockdown of DGAT1 gene significantly inhibited the TNF-alpha expression.
      Finally, the DGAT1 expression levels were closely related to the TNF-alpha level
      in 3T3-L1 adipocytes.

PMID- 16956610
TI  - Haemozoin (beta-haematin) biomineralization occurs by self-assembly near the
      lipid/water interface.
AB  - Several blood-feeding organisms, including the malaria parasite detoxify haem
      released from host haemoglobin by conversion to the insoluble crystalline
      ferriprotoporphyrin IX dimer known as haemozoin. To date the mechanism of
      haemozoin formation has remained unknown, although lipids or proteins have been
      suggested to catalyse its formation. We have found that beta-haematin (synthetic
      haemozoin) forms rapidly under physiologically realistic conditions near
      octanol/water, pentanol/water and lipid/water interfaces. Molecular dynamics
      simulations show that a precursor of the haemozoin dimer forms spontaneously in
      the absence of the competing hydrogen bonds of water, demonstrating that this
      substance probably self-assembles near a lipid/water interface in vivo.

PMID- 16956611
TI  - CRM1 mediates nuclear export of HDAC7 independently of HDAC7 phosphorylation and
      association with 14-3-3s.
AB  - CRM1, 14-3-3 proteins, and CaMK play important roles in trafficking of HDAC7, but
      the interplay between these proteins in this process is not clearly understood.
      Here, we show that CRM1 is capable of promoting cytoplasmic localization of wild
      type and mutant HDAC7 (S178A/S344A/S479A), which is normally found in the
      nucleus. Using phospho-specific antibodies to HDAC7, we demonstrate that CaMK I
      promotes phosphorylation of S178, S344, and S479 of HDAC7. We also show that
      endogenous S178-phosphorylated HDAC7 is localized in both the nucleus and the
      cytoplasm, whereas S344- and S479-phosphorylated HDAC7 are exclusively localized
      in the nucleus. An HDAC7 mutant, S178E/S344E/S479E, which lost the ability to
      bind 14-3-3s, is localized in both the nucleus and the cytoplasm. Furthermore,
      the nuclear export of S178E/S344E/S479E is inhibited by LMB, but is enhanced by
      the CRM1. Taken together, these results strongly suggest that CRM1 mediated
      nuclear export of HDAC7 is independent of HDAC7 phosphorylation and its
      association with 14-3-3s.

PMID- 16956612
TI  - Large scale nonlinear optimization for asymmetric operation and design of
      Simulated Moving Beds.
AB  - Simulated Moving Bed (SMB) was developed as a realization of continuous
      countercurrent operation of chromatographic separation. An SMB unit consists of
      several columns of the same length connected in series, where feed and desorbent
      are supplied and extract and raffinate are withdrawn continuously. This operation
      is repeated by shifting the supply/withdrawal points at a regular interval,
      making the operation symmetric. In this study, we explore asymmetric operation
      and design through a full-cycle optimization model, where the operation of the
      entire cycle is described within a nonlinear programming (NLP) problem and the
      Partial Differential Algebraic Equations (PDAEs) are fully discretized both in
      temporal and spatial domains. The NLP problem is implemented within the AMPL
      modeling environment and is solved using IPOPT, an interior-point NLP solver. We
      found that this problem is solved efficiently, and introducing a full-cycle
      formulation has the potential to improve the performance of SMB, as shown through
      single and multi-objective optimization studies.

PMID- 16956613
TI  - Isotope dilution high-resolution gas chromatography/high-resolution mass
      spectrometry method for analysis of selected acidic herbicides in surface water.
AB  - In this work, an isotope dilution method for determination of selected acidic
      herbicides by high-resolution gas chromatography/high-resolution mass
      spectrometry (HRGC/HRMS) was developed for surface water samples. Average percent
      recoveries of native analytes were observed to be between 70.8 and 93.5% and
      average recoveries of labeled quantification standards [(13)C(6)]2,4-D and
      [(13)C(6)]2,4,5-T were 85.5 and 101%, respectively. Using this method, detection
      limits of 0.05 ng/L for dicamba, MCPA, MCPP, and triclopyr, and 0.5 ng/L for 2,4
      D were routinely achieved. The method was applied to measuring the concentration
      of these analytes in surface water samples collected from five sampling locations
      in the Lower Fraser Valley region of British Columbia, Canada. All of the
      herbicides monitored were detected at varying levels in the surface water samples
      collected. The highest concentrations detected for each analyte were 345 ng/L for
      2,4-D, 317 ng/L for MCPA, 271 ng/L for MCPP, 15.7 ng/L for dicamba, and 2.18 ng/L
      for triclopyr. Average detection frequencies of the herbicides were 95% for MCPA,
      80% for MCPP, 70% for dicamba, 65% for 2,4-D, and 46% for triclopyr. Seasonal
      variations of herbicide levels are also discussed.

PMID- 16956614
TI  - Evaluation of multidimensional capillary electrophoretic methodologies for
      determination of amino bisphosphonate pharmaceuticals.
AB  - Alendronate and pamidronate are amino bisphosphonate analogues of pyrophosphate
      used for the treatment of a variety of bone diseases. Analysis of these compounds
      is problematic due to their polar ionic nature, lack of a suitable chromophore
      and chelation properties and current analytical approaches involve extensive
      sample preparation and derivatization procedures. The potential of
      multidimensional capillary electrophoretic methodological approaches, which
      eliminate sample preparation have been evaluated for the analysis of these
      compounds both in aqueous and urinary matrices. Capillary isotachophoresis (cITP)
      was employed as a pre-separation and on-line sample concentration step prior to
      analytical determination using either cITP or capillary zone electrophoresis
      (CZE) with conductivity detection. Single cITP, cITP-cITP and cITP-CZE approaches
      were partially validated with respect to repeatability, recovery and linearity of
      response for both compounds. The increases in sensitivity achievable through
      increasing injection volume from 30 to 300 microL may render such strategies
      appropriate for determination of these agents at biologically relevant
      concentrations with minimal sample work-up.

PMID- 16956615
TI  - Reversed-phase liquid chromatograhy/electrospray ionization tandem mass
      spectrometry for analysis of perchlorate in water.
AB  - A new reversed-phase liquid chromatograhy/electrospray ionization tandem mass
      spectrometry method was developed for the analysis of perchlorate in water. The
      improved separation of perchlorate from common anions along with sample dilution
      effectively reduced matrix effects, primarily ion suppression caused by common
      anions. The (18)O-enriched perchlorate used as an internal standard provided
      further compensation for potential changes associated with instrument
      sensitivity, retention time shifting, peak broadening, ion suppression, and other
      matrix effects. The mean recoveries and relative standard deviations were 92-107%
      and 2.5-9.5% for simulated water matrix spikes at 0.05-1.0 microg/L, and 80-106%
      and 3.8-13% for real water sample matrix spikes at 2.0 microg/L, respectively.
      The method detection limits were 0.007 microg/L for reagent water and 0.014
      microg/L for the simulated water matrix that contained 100 mg/L of SO(4)(2-),
      CO(3)(2-), and Cl(-) anions; 2 mg/L of PO(4)(3-) as P and NO(3)(-) as N; and 0.1
      mg/L of Br(-), BrO(3)(-), ClO(2)(-), ClO(3)(-), and F(-) anions in reagent water,
      respectively. When using cartridge pretreatment to remove problematic SO(4)(2-),
      CO(3)(2-), and Cl(-) anions, the minimum reporting level could be set to 0.05
      microg/L or lower. With 10-fold dilution, the minimum reporting level was
      conservatively set to 0.5 microg/L.

PMID- 16956616
TI  - Uronic acid determination by high performance liquid chromatography with
      postcolumn fluorescence derivatization.
AB  - To develop a fluorimetric high performance liquid chromatography (HPLC) technique
      for uronic acid microanalysis, a saline mobile phase and the postcolumn
      fluorimetric determination were combined. The detection limits of D-glucuronic, D
      galacturonic and D-mannuronic acids were 7.19, 23.88 and 7.08 pmol, respectively.
      The proposed method was successfully applied to uronic acid microanalysis in a
      polysaccharide hydrolysate and a drink.

PMID- 16956617
TI  - Application of gas chromatography-hybrid chemical ionization mass spectrometry to
      the analysis of diclofenac in wastewater samples.
AB  - Hybrid chemical ionization (HCI), a new and useful alternative to conventional
      chemical ionization mass spectrometry, has been applied to the analysis of the
      pharmaceutical diclofenac in wastewater samples. This technique takes advantage
      of the high versatility of ion trap (IT) spectrometers combined with external
      ionization sources. In hybrid configuration, reagent ions are generated in the
      external source through electron ionisation (EI) of a reagent gas. These reagent
      ions are then drawn into the ion trap and only those selected are allowed to
      react with analytes eluting from the GC column. These ion-molecule reactions
      create analyte ions which are held in the ion trap. In this study ion-molecule
      reactions between C(3)F(5)(+) cations, generated from perfluorotributylamine
      (FC43), and diclofenac molecules have been investigated. The observed reaction
      products were [M+C(3)F(5)-H(2)O](+) adduct ions, which result from the initial
      electrophilic addition of C(3)F(5)(+) cations to the diclofenac molecule followed
      by the rapid loss of H(2)O. Further fragmentation of these ions by MS/MS yielded
      enough daughter ions for a reliable identification of diclofenac in complex
      matrices. The GC-HCI-MS/MS method applied to wastewater samples provided highly
      enhanced selectivity and sensibility, with a detection limit in real samples of
      3.0 ng/L, for a solid-phase extraction (SPE) pre-concentration factor of 400.
      Other performance characteristics of the method, such as linearity and precision
      were also satisfactory. Finally, the method was successfully applied to the
      analysis of wastewater samples taken from the effluent of an urban sewage
      treatment plant (STP).

PMID- 16956618
TI  - Distribution of viral antigens and development of lesions in chicken embryos
      inoculated with nipah virus.
AB  - An isolate of Nipah virus was injected into fertile eggs via the allantoic cavity
      or yolk sac. Allantoic inoculation resulted in considerable pathological
      variation and only partial mortality. Dead embryos showed severe necrosis in the
      brain and congestion in the kidney and the subcutis of limbs. In contrast, yolk
      sac inoculation led to uniform infection and mortality, the dead embryos
      exhibiting the same lesions as those described above but without the subcutaneous
      congestion. Histological lesions in dead embryos inoculated by either route were
      similar and particularly severe in the central nervous system. Viral antigens
      were detected mainly in the vasculature and neurons. The results indicated that
      Nipah virus is highly pathogenic to chicken embryos, and that the route of
      inoculation is an important determinant of the course of disease. The findings
      also suggested that yolk sac inoculation can be used for viral titration, and
      that the chicken embryo represents a useful model for studying the vascular and
      neuronal tropisms of Nipah virus.

PMID- 16956619
TI  - Evidence of a maternal effect that protects against water stress in larvae of the
      American dog tick, Dermacentor variabilis (Acari: Ixodidae).
AB  - We report that the ability to absorb water vapor from the air in larvae of the
      American dog tick, Dermacentor variabilis, changes depending upon moisture
      conditions where the eggs develop. When development occurs at lower relative
      humidities, resultant larvae can replenish water stores, maintain water balance,
      and survive at relative humidities as low as 75-85% RH, a range that agrees with
      previously published values for the critical equilibrium humidity or CEH. In
      contrast, exposure to high relative humidity conditions during development
      elevates the CEH to 93-97% RH. These larvae can survive only at relative
      humidities that are close to saturation, as 93% RH is a dehydrating atmosphere.
      For these larvae, absorption at 97% RH can be prevented by blocking the
      mouthparts with wax, indicating that an upward shift has occurred in the moisture
      threshold where the active mechanism for water vapor absorption operates. Based
      on transfer experiments between low and high relative humidities, the CEH of
      larvae is determined by the relative humidity experienced by the mother rather
      than the moisture conditions encountered by eggs after they are laid. The fact
      that no changes in body water content, dehydration tolerance limit and water loss
      rate were observed implies that adjustments to the CEH conferred by the mother
      have the adaptive significance of enabling larvae to maintain water balance by
      limiting the range of hydrating atmospheres.

PMID- 16956620
TI  - The folding energy landscape of the dimerization domain of Escherichia coli Trp
      repressor: a joint experimental and theoretical investigation.
AB  - Enhanced structural insights into the folding energy landscape of the N-terminal
      dimerization domain of Escherichia coli tryptophan repressor, [2-66]2 TR, were
      obtained from a combined experimental and theoretical analysis of its equilibrium
      folding reaction. Previous studies have shown that the three intertwined helices
      in [2-66]2 TR are sufficient to drive the formation of a stable dimer for the
      full-length protein, [2-107]2 TR. The monomeric and dimeric folding intermediates
      that appear during the folding reactions of [2-66]2 TR have counterparts in the
      folding mechanism of the full-length protein. The equilibrium unfolding energy
      surface on which the folding and dimerization reactions occur for [2-66]2 TR was
      examined with a combination of native-state hydrogen exchange analysis, pepsin
      digestion and matrix-assisted laser/desorption mass spectrometry performed at
      several concentrations of protein and denaturant. Peptides corresponding to all
      three helices in [2-66]2 TR show multi-layered protection patterns consistent
      with the relative stabilities of the dimeric and monomeric folding intermediates.
      The observation of protection exceeding that offered by the dimeric intermediate
      in segments from all three helices implies that a segment-swapping mechanism may
      be operative in the monomeric intermediate. Protection greater than that expected
      from the global stability for a single amide hydrogen in a peptide from the C
      helix possibly and another from the A-helix may reflect non-random structure,
      possibly a precursor for segment swapping, in the urea-denatured state. Native
      topology-based model simulations that correspond to a funnel energy landscape
      capture both the monomeric and dimeric intermediates suggested by the HX MS data
      and provide a rationale for the progressive acquisition of secondary structure in
      their conformational ensembles.

PMID- 16956622
TI  - Anxiety sensitivity: prospective prediction of panic attacks and Axis I
      pathology.
AB  - Emerging evidence suggests that anxiety sensitivity (AS) predicts subsequent
      development of anxiety symptoms and panic attacks. However, evidence regarding
      whether AS serves as a premorbid risk factor for the development of clinical
      syndromes is lacking. The primary aim of the present study was to determine
      whether AS acts as a vulnerability factor in the pathogenesis of psychiatric
      diagnoses. A large nonclinical sample of young adults (N=404) was prospectively
      followed over two years. The Anxiety Sensitivity Index (ASI: Reiss S, Peterson
      RA, Gursky DM, McNally RJ. Anxiety sensitivity, anxiety frequency, and the
      prediction of fearfulness. Behaviour Research and Therapy 1986; 24: 1-8.) and
      trait anxiety served as predictors. Consistent with prior reports, AS predicted
      the development of spontaneous panic attacks in those with no history of panic.
      Importantly, AS was found to predict the incidence of anxiety disorder diagnoses
      and overall Axis I diagnoses in those with no history of Axis I diagnoses at
      study entry. These are the first data to provide strong prospective evidence for
      AS as a risk factor in the development of anxiety disorders.

PMID- 16956621
TI  - Serum S100B and antioxidant enzymes in bipolar patients.
AB  - Bipolar disorder (BD) is a chronic, severe, and highly disabling psychiatric
      disorder; peripheral markers have been used to assess biochemical alterations
      associated with BD and/or possibly involved in its pathophysiology. Beyond
      neuronal commitment, many groups have proposed the involvement of glial activity
      in psychiatric disorders. Other biochemical markers, particularly associated with
      oxidative stress, have been studied in BD. In the present study, we evaluated
      glial involvement and oxidative stress in patients with BD. Glial activity was
      assessed by measuring serum S100B content; oxidative stress was assessed using
      serum thiobarbituric acid reactive substances (TBARS) and activities of
      antioxidant enzymes in BD patients during different episodes of disease. We found
      a significant increment of serum S100B during episodes of mania and depression,
      but not in euthymic patients. Superoxide dismutase (SOD) activity, as well the
      SOD/glutathione peroxidase plus catalase ratio, was also increased in manic and
      depressed patients. On the other hand, TBARS levels were increased in BD patients
      regardless of the phase of the disorder. These findings suggest a potential
      oxidative damage in BD patients. This peripheral oxidative imbalance indicates
      that systemic changes are taking place during the active phases of the illness.
      Such changes appear to relate to astrocyte function, as indicated by serum S100B
      elevation.

PMID- 16956623
TI  - The DEX/CRH neuroendocrine test and the prediction of depressive relapse in
      remitted depressed outpatients.
AB  - Hypothalamo-pituitary-adrenal (HPA) system dysfunction is the most characteristic
      biological alteration found in a majority of depressed patients. Accumulating
      evidence suggests that the combined dexamethasone (DEX)/corticotropin-releasing
      hormone (CRH) test is highly sensitive to detect HPA system abnormalities. The
      aim of this study was to evaluate whether the DEX/CRH test has a predictive value
      for the risk of depressive relapse in outpatients who are in clinical remission
      from a major depressive episode. Thirty-eight depressed outpatients (23 women, 15
      men) in remission (MADRS score < or =8) underwent the DEX/CRH test and were
      followed up for 12 months regarding the occurrence of a new depressive episode.
      In parallel we recruited 24 controls (13 men and 11 women). The main result is a
      statistically significant difference concerning the delta and AUC numbers for
      cortisol plasmatic values between the group of patients who relapsed during the 1
      year follow-up and control subjects, but not between the group of patients with
      prolonged remission and controls. These results suggest that in outpatients who
      are in clinical remission from a major depressive episode, high delta and AUC
      values in the DEX/CRH test compared to controls subjects can be associated with a
      higher risk of relapse.

PMID- 16956624
TI  - A critique of thermal modeling of snake infrared reception by Jones, Lynn and
      Stone (2001).

PMID- 16956625
TI  - Aortic-banding induces myocardial oxidative stress and changes in concentration
      and activity of antioxidants in male Wistar rats.
AB  - Myocardial activity and gene expression of antioxidant defenses and oxidative
      damage were examined in an experimental model of pressure overload hypertrophy.
      Male Wistar rats were divided into abdominal aortic-banded or sham-operated
      groups. After 30 days, arterial pressure and heart rate were measured. Heart,
      lung, and liver were extracted and weighted to evaluate cardiac hypertrophy and
      pulmonary and hepatic congestion. Heart homogenates were prepared to quantify
      lipid peroxidation (LPO); the activities of superoxide dismutase (SOD), catalase
      (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx) and
      glutathione reductase (GR); and Cu-Zn SOD and GST concentrations. Total
      glutathione (GSH) myocardial content was also measured. Arterial pressure (142 +/
      17 mmHg) and cardiac hypertrophy index (3.4 +/- 0.45 mg/g) were significantly
      increased (by 38% and 22%, respectively, p<0.0001) in the aortic-banded group.
      LPO was enhanced by 55% in the aortic-banded group (11891 +/- 766 cps/mg protein,
      p<0.001) compared with that in the controls. SOD activity and concentration were
      higher (40% and 38%, 15.15 +/- 1.03 U/mg protein, 49.187 pixels, respectively,
      p<0.05) in the aortic-banded group than in the controls. Aortic-banding induced a
      decrease by 28% in GST (48 +/- 10 pmol/min/mg protein, p<0.005), by 36% in GPx
      (38.2 +/- 9.5 nmol/min/mg protein, p<0.005), by 31% in GR activities (1.55 +/-
      0.23 nmol/mg protein, p<0.0005), and by 43% in GSH content (0.13 +/- 0.02 nmol/mg
      protein, p<0.005). In conclusion, in this model it was observed that myocardial
      oxidative stress induces alterations in antioxidant enzyme activities and protein
      expression. The follow up of these parameters could afford an early therapeutical
      window to avoid heart failure progression.

PMID- 16956626
TI  - Vascular endocan is preferentially expressed in tumor endothelium.
AB  - Endothelial cell phenotypes are differentially regulated between different sites
      of the vascular tree. We tested the hypothesis that endocan, a novel soluble
      dermatan sulfate proteoglycan, is differentially expressed in the intact
      endothelium and that site-specific expression is mediated by signals in the local
      microenvironment. Using a combination of Northern blot analyses, Taqman RT-PCR,
      and in situ hybridizations, endocan was shown to be preferentially expressed in
      the endothelial lining of tumor xenografts, including human non-small cell lung
      cancer, rat glioma, and human renal cell carcinoma. In contrast, endocan mRNA was
      expressed at low levels in embryos between E4.5 and E18.5. Under in vitro
      conditions, endocan expression in human umbilical vein endothelial cells (HUVEC)
      was upregulated by tumor cell-conditioned medium, an effect that was inhibited by
      the addition of neutralizing antibody to vascular endothelial growth factor
      (VEGF). Moreover, treatment of HUVEC with VEGF resulted in a dose- and time
      dependent increase in endocan mRNA. The results suggest that endocan is
      preferentially expressed in tumor endothelium in vivo and that its expression is
      regulated by tumor-derived factors.

PMID- 16956627
TI  - Gender and obesity influence sodium intake and fluid regulation in Zucker rats
      following repeated sodium depletions.
AB  - The Zucker obese rat is an important model for the metabolic syndrome, which
      includes renal disease and salt-sensitive hypertension, suggesting abnormalities
      of body fluid regulation. Here, in Zucker rats, lean and obese, and of both
      sexes, we compared 48 h of sodium intake and fluid regulation responses with
      repeated depletions with furosemide to repeated control saline injections.
      Increased urine volume excretion was observed after each furosemide
      administration for the 4 groups and obese rats excreted more than the leans on
      the control days. Male obese rats did not excrete sodium nor increase intake of
      2% NaCl following the first furosemide administration, whereas the other 3 groups
      did. Subsequent depletions increased 2% NaCl consumption and urinary sodium
      excretion in all groups. Males excreted more sodium in their urine than the
      females on the control days. Females showed an increase in 2% NaCl intake on
      control days. Water intake increased in the female leans after each depletion,
      increased in the males after the 2nd and 3rd depletion and increased in the obese
      females only after the 2nd depletion. These findings show clearly that there are
      gender- and weight-related differences in the response of Zucker rats to
      furosemide-induced depletion. However, the main differences occurred with the
      first depletion. With repeated depletions the rats adjusted sodium and fluid
      intake and excretion so that differences due to gender and body weight tended to
      disappear. Our findings caution against drawing conclusions about differences due
      to gender and body weight based on single treatments.

PMID- 16956628
TI  - Weight gain and maternal behavior in CCK1 deficient rats.
AB  - The OLETF rat model of obesity has been extensively studied as an adult model of
      hyperphagia-induced obesity. In order to better understand the early
      circumstances that make OLETF pups obese, we investigated body weight from
      postnatal day (PND) 1 and examined diurnal maternal behavior over the first three
      postpartum weeks by undisturbed observations. Male and female OLETF rats weighed
      significantly more than LETO controls from PND 1 until adulthood. Differences in
      nursing behavior were observed only in the third postnatal week: OLETF dams
      exhibited more frequent nursing. OLETF dams displayed less self-directed
      behaviors and activity, over the entire postpartum period examined. Taken
      together, these data demonstrate that OLETF males and females are heavier from
      birth and suggest that maternal factors may contribute to weight differences
      between the strains.

PMID- 16956629
TI  - Bioactive flavonoids and saponins from Climacoptera obtusifolia.
AB  - Two bidesmosidic saponins were isolated from Climacoptera obtusifolia
      (Chenopodiaceae) and their structures were determined as gypsogenin 3-O-[beta-D
      xylopyranosyl-(1-->3)-beta-D-glucopyranoside]-28-O-{beta-D-glucopyranosyl} ester
      (1) and hederagenin 3-O-[beta-D-xylopyranosyl-(1-->3)-beta-D-glucopyranoside]-28
      O-[beta-D-glucopyranosyl} ester (2), by spectroscopic methods. Two known
      compounds, isorhamnetin 3-O-beta-D-glucopyranoside (3), and isorhamnetin 3-O
      [alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (4) were also isolated
      for the first time from this plant. Compounds 1-4 were tested in various
      immunomodulatory assays. Compound 2 suppressed (92%) the reactive oxygen species
      (ROS) production on mononuclear cells in luminol-based chemiluminescence (CL)
      assay at a higher concentration (50 microg/mL). Compounds 3 and 4 demonstrated a
      strong inhibition on ROS production in the oxidative burst activity of whole
      blood, neutrophils, and mononuclear cells. Additionally compounds 3 and 4 also
      suppressed PHA T-cell proliferation with no cytotoxic effects.

PMID- 16956630
TI  - Antimicrobial metabolites produced by an intertidal Acremonium furcatum.
AB  - In a screening for antimicrobial metabolites, amides of D-allo- and L-isoleucine
      derivatives were isolated from the culture of a marine strain of Acremonium
      furcatum. Structural elucidation of these compounds was performed by analysis of
      spectroscopic data and confirmed by synthesis. All of the compounds, natural and
      synthetic intermediates, were bioassayed against bacteria and phytopathogenic
      fungi, with many showing remarkable antifungal activities.

PMID- 16956631
TI  - Comparative phytochemical characterization of three Rhodiola species.
AB  - In comparison to the well-recognized adaptogenic herb Rhodiola rosea,
      phytochemical constituents of two other Rhodiola species (R. heterodonta and R.
      semenovii) were elucidated and characterized. Two major phytochemical groups;
      phenolic and/or cyanogenic glycosides and proanthocyanidins, were isolated and
      identified in the three species. Chemical similarities among the three species
      were observed; however, each species displayed differences in phytochemical
      constituents. R. heterodonta contained a newly detected phenylethanoid glycoside,
      heterodontoside, in addition to the known compounds tyrosol, viridoside,
      salidroside, and rhodiocyanoside A. Both R. heterodonta and R. rosea contained
      phenylethanoid/propanoid compounds that were not detected in R. semenovii. For R.
      semenovii, the cyanogenic glucosides rhodiocyanoside A and lotaustralin were
      detected. Although the three species have proanthocyanidins composed of (-)
      epigallocatechin and its 3-O-gallate esters in common, the degree of
      polymerization greatly differed between them. In contrast to R. heterodonta and
      R. semenovii, R. rosea has higher molecular weight polymeric proanthocyanidins.
      This study resulted in the identification and isolation of phytochemical
      constituents for direct cross-comparison between three Rhodiola species of
      medicinal and pharmacological value.

PMID- 16956632
TI  - Biotransformations of ent-18-acetoxy-6-ketomanoyl oxides epimers at C-13 with
      filamentous fungi.
AB  - Two ent-18-acetoxy-6-oxomanoyl oxides, epimers at C-13, have been prepared from
      ent-6alpha,8alpha,18-trihydroxylabda-13(16),14-diene (andalusol), isolated from
      Sideritis foetens, by means of several chemical pathways and a regioselective
      acylation with Candida cylindracea lipase (CCL). Biotransformation of these 13
      epimeric ent-manoyl oxides by Fusarium moniliforme and Neurospora crassa produced
      mainly ent-1beta- or ent-11alpha-hydroxylations, as well as their deacetylated
      derivatives, in both epimers. In addition, with the 13-epi substrate N. crassa
      originated other minor hydroxylations by the ent-alpha face at C-1 or at C-12,
      whereas an ent-11beta-hydroxyl group, probably originated by reduction of an 11
      oxo derivative also isolated, was achieved with the 13-normal substrate.

PMID- 16956633
TI  - Uncovering the complex metabolic network underlying diterpenoid phytoalexin
      biosynthesis in rice and other cereal crop plants.
AB  - Rice (Oryza sativa) is a staple food crop and serves as a model cereal crop plant
      for scientific study. Phytochemical investigations of the agronomically
      devastating rice blast disease have identified a number of rice phytoalexins
      exhibiting significant direct anti-fungal activity against the causative agent,
      Magneporthe grisea. Current evidence strongly indicates that these phytoalexins,
      largely a family of labdane-related diterpenoids, are important as general
      antibiotics, and that similar phytoalexins are produced more broadly throughout
      the cereal crop family. From the extensive sequence information available for
      rice it has been possible to functionally identify the genes for the enzymes
      catalyzing the two consecutive cyclization reactions that initiate biosynthesis
      of these labdane-related diterpenoid phytoalexins. This has led to several
      insights into the underlying evolution of diterpene biosynthesis throughout the
      cereal crop family. The hydrocarbon olefins resulting from cyclization must be
      further elaborated to form bioactive natural products and, because not much is
      currently known, necessarily speculative biosynthetic pathways for these
      processes are presented. Given the significant antibiotic activity of the labdane
      related diterpenoid phytoalexins from rice, and the presence of similar secondary
      metabolism throughout the cereal crop plant family, study of this type of
      biosynthesis will continue to be an area of active investigation.

PMID- 16956634
TI  - Terpenoids from Juniperus polycarpus var. seravschanica.
AB  - Two eudesmanes, two abietanes, two podocarpanes and other nine known compounds
      were isolated from the dried fruits of Juniperus polycarpus var. seravschanica.
      Their structures were established on the basis of analysis of spectroscopic
      evidence. Some of the isolated terpenoids showed antimalarial activity.

PMID- 16956635
TI  - Phytochemical and genetic analysis in selected chemotypes of Withania somnifera.
AB  - The main active components and genetic profile of 15 selected accessions of
      Withania somnifera Dunal. were analysed. Ethanolic extract of the dried
      roots/leaves of the plant was concentrated under pressure at 50+/-5 degrees C and
      was analysed for main compounds (withanolides and withaferin A) by HPLC. All the
      main components were found to be present in accessions (AGB 002, AGB 009, RSS
      009, RSS 033). Correlation of these main components with their genetic factors,
      was undertaken using AFLP (amplified fragment length polymorphism) markers. Among
      64 primers 7 yielded optimum polymorphism. A total of 913 polymorphic peaks were
      generated using these primers. Jaccard's similarity coefficient indicated that
      accessions having almost the same active compounds clustered together. The
      present study demonstrates that AFLP can be successfully used to resolve the
      correlation of AFLP data with the presence of secondary metabolites.

PMID- 16956636
TI  - Lectin histochemical characterisation of the porcine small intestine around
      weaning.
AB  - The present study was undertaken to characterise the carbohydrate profile of the
      porcine small intestine using lectin histochemistry during the period from 3 days
      prior to weaning to 9 days post-weaning. A total of 56 piglets weaned at 4 weeks
      of age were included in the experiment. The most prominent changes in the
      glycosylation pattern were observed in the goblet cells. The highest lectin
      reactivity of the goblet cells in the crypts was observed 7 days post-weaning
      which suggests that the protective effect of the mucus layer against pathogenic
      bacteria is increasing during the postweaning period. The staining pattern of the
      apical membrane remained unchanged during the experimental period. This indicates
      that the glycosylation process in the goblet cells is rapidly inducible whereas
      changes in the glycosylation pattern of the apical membrane requires more time.
      The glycosylation pattern of both goblet cells and apical membrane differed
      between the positions of the small intestine. As glycoconjugates can act as
      attachment sites for microorganisms, these differences in the distribution of
      sugar residues may be one explanation for the site-specificity of certain
      pathogens.

PMID- 16956637
TI  - Differential effects of pyrethroid insecticides on extracellular dopamine in the
      striatum of freely moving rats.
AB  - In order to obtain a more complete understanding of pyrethroid neurotoxicity,
      effects of the pyrethroid insecticides, allethrin (type I), cyhalothrin (type II)
      and deltamethrin (type II) on extracellular levels of dopamine (DA) and its
      metabolites in the striatum of conscious rats were studied by in vivo
      microdialysis. Rats were treated i.p. with pyrethroids or vehicle. Allethrin had
      a dual effect on DA release. The increase in the extracellular level of striatal
      DA by 10 mg/kg allethrin reached a maximum of 178% of baseline but 20 and 60
      mg/kg inhibited DA release to 63% and 52% of baseline with a peak effect at 60-80
      min after injection. Cyhalothrin 10, 20 and 60 mg/kg inhibited DA release to 65%,
      56% and 45% of basal release, respectively, with a peak time of inhibition 40-80
      min past injection. Deltamethrin (10 and 20 mg/kg) increased DA release to
      maximum of 187% and 252% of basal release whereas 60 mg/kg first reduced the
      efflux for 40 min to 50% of basal release and then increased the efflux to a
      maximum of 344% of basal release with a peak time of 120 min. Local infusion of 1
      microM tetrodotoxin, a Na(+) blocker through the dialysis probe completely
      prevented the effect of allethrin (10 and 60 mg/kg), cyhalothrin (60 mg/kg) and
      deltamethrin (20 mg/kg) on DA release but only partially blocked the effects of
      60 mg/kg deltamethrin. The effect of deltamethrin (60 mg/kg) on DA release was
      completely prevented by local infusion of 10 microM nimodipine, an L-type Ca(++)
      channel blocker. All three pyrethroids did not alter the extracellular levels of
      DOPAC, 3-MT and HVA except that 20 and 60 mg/kg of allethrin and cyhalothrin
      increased 3-MT levels. Effect of the pyrethroids on synaptosomal DA uptake was
      also examined. The DA uptake was decreased in rats exposed to 60 mg/kg of
      allethrin and cyhalothrin but was increased in rats exposed to 60 mg/kg of
      deltamethrin. Our results demonstrate that striatal DA release and DA uptake are
      differentially affected by type I and the two type II pyrethroids indicating that
      dopaminergic circuitry, striatal DA in particular, may be a pyrethroid target and
      that pyrethroids may be acting on striatal DA by multiple mechanisms.

PMID- 16956638
TI  - Simultaneous tracing of 76Se-selenite and 77Se-selenomethionine by absolute
      labeling and speciation.
AB  - Nutritional selenocompounds are transformed into the assumed common intermediate
      selenide, which is utilized for the synthesis of selenoenzymes or transformed
      into methylated metabolites for excretion. Hence, selenocompound metabolites can
      be traced only with labeled selenium. Here we applied a new tracer method for the
      metallomics of biometals using simultaneous speciation of each metallome labeled
      with different homo-elemental isotopes to metabolism and availability of
      selenium. Rats were depleted of endogenous natural abundance selenium by feeding
      a single selenium stable isotope ((82)Se-selenite) and then administered (76)Se
      selenite and (77)Se-selenomethionine ((77)Se-SeMet)simultaneously. Biological
      samples were subjected to quantification and speciation analysis by HPLC-ICPMS.
      Metabolites of the labeled (76)Se and (77)Se and interaction with endogenous
      selenium were traced and examined without interference from the corresponding
      endogenous natural abundance isotopes. Differences in the distribution and
      metabolism among organs and between the two nutritional selenocompounds were
      compared under exactly identical biological and analytical conditions: (1)
      selenite was distributed more efficiently than SeMet in organs and body fluids
      except the pancreas. (2) SeMet was taken up by organs in its intact form. (3)
      Selenium of SeMet origin was distributed selectively in the pancreas and mostly
      bound to a protein together with intact SeMet. (4) Selenosugars A and B but not
      trimethylselenonium (TMSe) were detected in the liver. (5) Selenosugar B and TMSe
      were detected in the kidneys.

PMID- 16956639
TI  - Investigation of destruxin A and B from 80 Metarhizium strains in China, and the
      optimization of cultural conditions for the strain MaQ10.
AB  - The production levels of destruxin A and B (DA and DB) of 80 Metarhizium strains
      from China were investigated. The average yields of DA and DB were 14.87+/-2.30
      and 3.65+/-0.58 microg/mL, respectively. The strains isolated from soil had
      significantly (p<0.05) lower production of DA and DB than the strains isolated
      from insect cadavers. Also, there was a positive correlation in the yields of DA
      and DB, and the regressive equations were established. Of the 80 strains, MaQ10
      had the highest yields of DA and DB, amounted to 106.78+/-9.41 and 29.52+/-2.63
      microg/mL, respectively, at 10 days fermentation period. Followed by the strains
      MaQ05, MaQ07 and MaQ12, their yields of DA were 79.72+/-5.36, 77.69+/-8.54 and
      70.04+/-10.1 microg/mL, respectively, and DB were 16.81+/-1.51, 13.38+/-0.41 and
      16.88+/-1.15 microg/mL, respectively. Furthermore, the cultural conditions of
      MaQ10 were optimized to produce DA and DB. The optimal inoculum, initial pH,
      temperature and rotary speed were 8%, pH 9.0, 27 degrees C and 240 r/min for DA,
      and 8%, pH 9.0, 25 degrees C and 220 r/min for DB. Under these optimal culture
      conditions, the predicted production of DA and DB was 193.87 and 39.85 microg/mL,
      and the actual production was 189.13 and 43.35 microg/mL, respectively.

PMID- 16956640
TI  - Immunogenicity of a plant-derived edible rotavirus subunit vaccine transformed
      over fifty generations.
AB  - Major efforts have been put forth for the development of effective rotavirus
      vaccines including transgenic plant vaccines. Previous studies have reported that
      rotavirus VP7 maintains its neutralizing immunity when it is transformed into the
      potato genome. The present study was aimed at investigating the hereditary
      stability of VP7-transformed potatoes over fifty generations. The VP7 gene was
      stably transcribed and expressed in potato cells as detected by RT-PCR and
      Western blotting. Humeral and mucosal responses were successfully induced in
      BALB/c mice fed with the fiftieth generation transformed potato tubers. There
      were no significant differences in serum IgG and fecal IgA between the mice fed
      with the first and fiftieth generation potatoes (P>0.05). Profiles of cytokines
      such as IFN-gamma, IL-2, IL-4, IL-5 and TGF-beta in immunized mice showed a naive
      T-cells bias to Th1 and Th3 polarization. Moreover, specific CTL responses were
      also detected in C57BL/6 mice fed with transformed potatoes. This research
      represents a significant step towards the development of rotavirus vaccines
      derived from a transgenic plant that can be obtained by long-term and large-scale
      vegetative reproduction. To our knowledge, this is the first finding regarding
      vaccines derived from plants that can be propagated for many generations.

PMID- 16956641
TI  - Immunoglobulin A antibodies against internal HIV-1 proteins neutralize HIV-1
      replication inside epithelial cells.
AB  - We show that intraepithelial cell neutralization of HIV by IgA antibodies to
      internal viral proteins can occur during antibody transcytosis from the
      basolateral to the apical surface. Polarized epithelial cells expressing the
      polymeric immunoglobulin receptor (pIgR) were transfected with HIV proviral DNA,
      and IgA was added to the basolateral side. Transcytosing IgA antibodies against
      Gag and RT significantly inhibited HIV replication as assessed by infection of
      HeLa-CD4-LTR/beta-Gal cells and direct p24 assay. Consistent with intracellular
      neutralization, colocalization of the internal virus proteins and their IgA
      antibodies was demonstrated by confocal microscopy. Thus, at least in the context
      of infections of polarized epithelia, antibody-mediated neutralization may not be
      restricted to viral surface antigens.

PMID- 16956642
TI  - Using satellite imagery for stormwater pollution management with Bayesian
      networks.
AB  - Urban stormwater runoff is the primary source of many pollutants to Santa Monica
      Bay, but its monitoring and modeling is inherently difficult and often requires
      land use information as an intermediate process. Many approaches have been
      developed to estimate stormwater pollutant loading from land use. This research
      investigates an alternative approach, which estimates stormwater pollutant
      loadings directly from satellite imagery. We proposed a Bayesian network approach
      to classify a Landsat ETM(+) image of the Marina del Rey area in the Santa Monica
      Bay watershed. Eight water quality parameters were examined, including: total
      suspended solids, chemical oxygen demand, nutrients, heavy metals, and oil and
      grease. The pollutant loads for each parameter were classified into six levels:
      very low, low, medium low, medium high, high, and very high. The results provided
      spatial estimates of each pollutant load as thematic maps from which the greatest
      pollutant loading areas were identified. These results may be useful in
      developing best management strategies for stormwater pollution at regional and
      global scales and in establishing total maximum daily loads in the watershed. The
      approach can also be used for areas without ground-survey land use data.

PMID- 16956643
TI  - Speciation of five arsenic species (arsenite, arsenate, MMAAV, DMAAV and AsBet)
      in different kind of water by HPLC-ICP-MS.
AB  - A method using Ion Chromatography hyphenated to an Inductively Coupled Plasma
      Mass Spectrometer has been developed to accurately determine arsenite (As(III)),
      arsenate (As(V)), mono-methylarsonic acid (MMAA(V)), dimethylarsinic acid
      (DMAA(V)) and arsenobetaine (AsBet) in different water matrices. The developed
      method showed a high sensitivity with detection limits for each arsenic species
      close to 0.4pg injected. Arsenite and arsenate were the major species found in
      surface and well waters, but AsBet and DMAA(V) were found in some surface waters,
      which has never been reported before, while in some natural mineral waters
      located in volcanic region, the arsenic content exceeded the maximal admissible
      arsenic content by European legislation standards and the predominant form was
      As(V).

PMID- 16956644
TI  - Solubilization of zinc compounds by the diazotrophic, plant growth promoting
      bacterium Gluconacetobacter diazotrophicus.
AB  - Gluconacetobacter diazotrophicus an endophytic diazotroph also encountered as
      rhizosphere bacterium is reported to possess different plant growth promoting
      characteristics. In this study, we assessed the zinc solubilizing potential of G.
      diazotrophicus under in vitro conditions with different Zn compounds using
      glucose or sucrose as carbon sources. G. diazotrophicus showed variations in
      their solubilization potential with the strains used and the Zn compounds tested.
      G. diazotrophicus PAl5 efficiently solubilized the Zn compounds tested and ZnO
      was effectively solubilized than ZnCO(3) or Zn(3)(PO(4))(2). The soluble Zn
      concentration was determined in the culture supernatant through Atomic Absorption
      Spectrophotometer. Gas chromatography coupled Mass Spectrometry analysis revealed
      5-ketogluconic acid, a derivative of gluconic acid as the major organic acid
      produced by G. diazotrophicus PAl5 cultured with glucose as carbon source. This
      organic anion may be an important agent that helped in the solubilization of
      insoluble Zn compounds.

PMID- 16956645
TI  - Municipal waste compost as an alternative to cattle manure for supplying
      potassium to lowland rice.
AB  - The importance of the use of potassium in agriculture is increasing in South Asia
      for making most productive use of the nutrient in terms of economic returns.
      Nutrient supply traditionally by cattle manure is constrained by its insufficient
      availability. Municipal waste compost may be an alternative source of nutrient
      supplements. Field experiments were conducted at the Experimental Farm of
      Calcutta University, West Bengal, India during the wet seasons of 1997, 1998 and
      1999 on flooded lowland rice. Potassium fractions in municipal waste compost and
      cattle manure were determined by sequential extraction and also the potassium
      uptake by rice to compare the effectiveness of municipal waste compost with
      traditional manure. Potassium was significantly bound to the organic matter in
      municipal waste compost. Potassium uptake by rice grain and straw increased
      significantly with the combined application of organics and fertilizers and it
      was higher in grain than in straw. Water-soluble and non-exchangeable potassium
      contents of municipal waste compost and cattle manure were highly correlated with
      the uptake of potassium by straw and grain. Exchangeable and residual potassium
      were also significantly correlated with the uptake of potassium by straw and
      grain of rice. Much higher uptake of K in rice straw and rain resulted from
      applying the manures in conjunction with fertilizers than when applied singly.

PMID- 16956646
TI  - Direct repeats in mitochondrial DNA and mammalian lifespan.
AB  - Mitochondria have long been suspected to be among the leading determinants of
      aging due to their functional importance and accelerated deterioration caused by
      accumulation of mutations in the mitochondrial DNA. Direct repeats are known to
      contribute to deletion formation in mtDNA and are a powerful source of reactive
      oxygen species (ROS)-independent mutagenesis. To evaluate the potential
      importance of homology-based deletion formation, we have analyzed the association
      between direct repeats in the mtDNA sequence and the lifespans of 65 mammalian
      species. Here, we report a significant negative correlation between the mutagenic
      potential of direct repeats and the mammalian lifespan, which is especially
      evident in closely related species.

PMID- 16956647
TI  - Methodological aspects of the induction of biofilms for remediation of the visual
      impact generated by quartz mining.
AB  - The opening up of mine faces causes severe alteration to the environment that
      must be remedied. In the case of quartz mines, the bright white colour of the
      mineral gives rise to a significant impact that is visible for long distances.
      New techniques to correct this visual impact, based on the induction of biofilms
      on the faces, have recently been developed in an attempt to imitate natural
      effects that mask the impact. Although techniques have been applied successfully
      in the laboratory, they must be optimized to ensure their success in the field.
      In the present study, the results of a randomized factorial experiment indicated
      that although the biofilms adhere to the faces naturally, without the use of
      adhesives, continued development of the film depends to a large extent on the
      input of nutrients. Water must also be provided with nutritional supplement to
      maintain the required level of moisture.

PMID- 16956648
TI  - Rapporteur report: Roundup, discussion and recommendations.
AB  - There is a relative paucity of recent information regarding the long-term health
      effects associated with exposure to ultrasound, and to infrasound and low
      frequency noise (LFN). For ultrasound, further epidemiological studies are
      recommended, and priority should be given to studies investigating the effects of
      handedness and to studies assessing possible subtle effects on brain function.
      These studies should reflect contemporary practises in diagnostic ultrasound and
      have sufficiently long follow-up periods to examine the possibility of effects
      into late adolescence or beyond. In the absence of a non-exposed control group,
      it would be advisable to make comparisons between a highly exposed group with a
      less exposed group, and to compare groups exposed at differing gestational
      stages. The effects associated with ultrasound contrast agents should also be
      studied, and the appropriateness of the thermal index (TI) and mechanical index
      (MI) should be reviewed. It is recommended that animal models should be used to
      investigate the effects of exposure at differing gestational ages on development,
      and modern cellular and molecular techniques used to investigate potential
      mechanisms of interaction. Although explicit morphological changes have been
      reported following occupational and experimental exposures to infrasound and low
      LFN, it was recommended that a thorough review of the relevant biological and
      health effects literature was necessary before specific proposals could be made.
      Uncertainties about the characterisation of these low frequencies also indicated
      the need to develop appropriate measurement techniques and protocols.

PMID- 16956650
TI  - Characterization of CSOC 882, a novel immortalized ovarian cancer cell line
      expressing EGFR, HER2, and activated AKT.
AB  - OBJECTIVE: Only a small number of comprehensively characterized immortalized
      ovarian cancer cell lines are available for laboratory studies on ovarian cancer.
      We describe a new ovarian cancer cell line that arose from primary culture of a
      stage IC, grade III ovarian carcinoma, designated CSOC 882. METHODS: We
      characterized CSOC 882 by karyotyping, growth modeling, immunohistochemical
      staining, immunoblotting, drug sensitivity testing, and xenografting in nude
      mice. RESULTS: CSOC 882 possessed an abnormal tetraploid karyotype including loss
      of one copy of chromosomes 2, 17, 19, and 21, and deletion of 8p21. Growth of
      CSOC 882 was best modeled using the logistic growth equation revealing an average
      doubling time of 31 h. CSOC 882 cells expressed vimentin, cytokeratin, p53,
      BRCA1, EGF receptor, HER2, androgen receptor, estrogen receptor alpha, and
      progesterone receptor, while no evidence of estrogen receptor beta or factor VIII
      was observed. Some but not all CSOC 882 cells were positive for CA125 reflecting
      the primary tumor, which had patchy CA125 staining. Drug sensitivity assays
      demonstrated that CSOC 882 was more sensitive to cisplatin and carboplatin than
      SKOV3 and HCC1937 while CSOC 882 and SKOV3 were both sensitive to paclitaxel
      unlike HCC1937. CSOC 882 xenografts retained the original characteristics of
      vimentin, cytokeratin, and factor VIII labeling. CONCLUSIONS: CSOC 882 is an
      immortalized cell line that has survived more than 130 passages in culture and
      retained molecular features of the primary tumor from which it was derived.
      Compared to the most common ovarian carcinoma cell lines, CSOC 882 is a unique
      resource for genetic and cellular research on ovarian cancer.

PMID- 16956651
TI  - More on intraperitoneal therapy.

PMID- 16956652
TI  - S1P regulation of ovarian carcinoma invasiveness.
AB  - OBJECTIVES: Within the tumor microenvironment the invasiveness of epithelial
      ovarian carcinoma (EOC) cells is stimulated by biologically active lipids such as
      lysophosphatidic acid (LPA). We tested the in vitro effect of another bioactive
      lysophospholipid, sphingosine-1-phosphate (S1P), on the invasiveness of EOC
      cells. METHODS: Dov13 EOC cells were tested for invasion through matrigel-coated
      chambers and for gelatinase activity using a fluorogenic assay. cDNA was analyzed
      through real-time PCR. Cell surface proteins, isolated through biotinylation and
      affinity purification, were analyzed by Western blots. RESULTS: Invasion of Dov13
      cells was enhanced by low (0.5 microM) and inhibited by high (20 microM)
      concentrations of S1P, which correlated with increased and reduced gelatinase
      activity in conditioned media. Low and high S1P dose also differently affected
      the presentation of surface S1P receptors; low S1P dose increased S1P1 and
      decreased S1P2, while high S1P increased S1P3. LPA and S1P differently altered
      transcript levels of their respective and reciprocal receptors; receptors that
      were upregulated by one lysophospholipid (S1P2,3 and LPA1 by LPA, LPA3,4 and
      S1P1,4,5 by S1P) were downregulated or unchanged by the other. CONCLUSIONS: The
      dual effect of high and low S1P concentration on invasion was probably caused by
      the diverse changes to the presentation of surface S1P receptors. The opposite
      effect of S1P and LPA on expression of each receptor suggests a homeostatic
      transcriptional mechanism that abrogates the effects of LPA and S1P on EOC cells.
      Altogether this study demonstrates a complex role of S1P in EOC cell invasion, a
      process highly balanced and regulated by LPA and S1P within the tumor
      microenvironment.

PMID- 16956653
TI  - Hypercalcemia induced by ovarian clear cell carcinoma producing all
      transcriptional variants of parathyroid hormone-related peptide gene during
      pregnancy.
AB  - BACKGROUND: Parathyroid hormone-related peptide (PTHrP) appears as the major
      causative agent responsible for the humoral hypercalcemia of malignancy (HHM).
      However, the use of promoters and splicing patterns of PTHrP gene in HHM have not
      been reported yet. CASE: A 35-year-old woman was diagnosed as an ovarian clear
      cell carcinoma with HHM caused by elevated serum PTHrP after delivery. An
      immunohistochemical study showed PTHrP expression in the tumor tissue. The
      Southern blot analysis following RT-PCR confirmed the presence of all types of
      PTHrP mRNA transcripts produced by a combination of three promoters, one 5'
      alternative splicing and three alternative 3' splicing events. CONCLUSION: An
      ovarian clear cell carcinoma induced PTHrP-related HHM, which resulted from the
      high expression of all isoforms for PTHrP gene.

PMID- 16956654
TI  - Lower risk of death from gastric cancer among participants of gastric cancer
      screening in Japan: a population-based cohort study.
AB  - OBJECTIVE: This study aimed to investigate the association between gastric cancer
      screening and mortality from gastric cancer. METHODS: In 1990, 47,605 Japanese
      subjects were recruited and completed a questionnaire about participation in
      gastric cancer screening and life-style. We followed up their vital status
      through December 2001. In this cohort, 41,394 subjects without a history of
      cancer were allocated to the screened group or the unscreened group according to
      their response to the question about gastric cancer screening. We estimated the
      relative risk (RR) of death from gastric cancer, death from any cause except
      gastric cancer, and incidence of gastric cancer with adjustment for potential
      confounding variables. RESULTS: The risk of death from gastric cancer among the
      screened group was significantly lower than that among the unscreened group. The
      multivariate RR of death from gastric cancer for screened individuals compared
      with those not screened was 0.54 (95% confidence interval [CI]: 0.38, 0.77). The
      RR of death from any cause except gastric cancer was 0.83 (95% CI: 0.77, 0.90),
      and the RR of incidence of gastric cancer was 0.94 (95% CI: 0.79, 1.13).
      CONCLUSION: Our data suggest that gastric cancer screening or factors associated
      with it may be associated with lower mortality from gastric cancer.

PMID- 16956655
TI  - Sperm DNA fragmentation in boars is delayed or abolished by using sperm
      extenders.
AB  - The semen quality of seven young adult boars was assessed for percentages of
      sperm motility, normal acrosomes, abnormal sperm, cells positive to sHOST (short
      Hipoosmotic Swelling Test), HPNA cells (sHOST Positive with Normal Acrosome
      cells) and the percentage of sperm heads, which exhibited DNA fragmentation using
      the Sperm Chromatin Dispersion test (SCD). These parameters were analysed in
      sperm samples both undiluted and diluted using a commercial extender and stored
      at 15 degrees C for 21 days. Results showed that semen quality decreases faster
      in the undiluted semen samples from day 0 to day 7 compared to diluted semen
      samples that remained with a high quality up to day 11. The undiluted semen
      exhibited a low DNA fragmentation index (DFI) during the first days and then a
      significant increase from day 7 up to day 21. This increase in the DFI coincided
      with the lowest levels of the other semen quality parameters. On the contrary,
      the samples diluted in the commercial extender showed very low levels of DNA
      fragmentation in all boars during the preservation period. When the evolution of
      DNA fragmentation was analysed in the undiluted samples, differences were found
      among boars. These differences were not shown in the samples diluted in the
      extender where the basal DFI remained stable during the 21 days. The main
      conclusion of this study was that some sperm extenders delay or partially prevent
      sperm DNA fragmentation.

PMID- 16956656
TI  - Sex ratio determination in bovine semen: a new approach by quantitative real time
      PCR.
AB  - Sex preselection of livestock offspring in cattle represents, nowadays, a big
      potential for genetic improvement and market demand satisfaction. Sperm sorting
      by flow cytometer provides a powerful tool for artificial insemination and
      production of predefined sexed embryos but, an accurate verification of the yield
      of sperm separation remains essential for a field application of this technique
      or for improvement and validation of other related semen sexing technologies. In
      this work a new method for the determination of the proportion of X- and Y
      bearing spermatozoa in bovine semen sample was developed by real time PCR. Two
      sets of primers and internal TaqMan probes were designed on specific X- and Y
      chromosome genes. To allow a direct quantification, a standard reference was
      established using two plasmid cDNA clones (ratio 1:1) for the specific gene
      targets. The method was validated by a series of accuracy, repeatability and
      reproducibility assays and by testing two sets of sorted and unsorted semen
      samples. A high degree of accuracy (98.9%), repeatability (CV=2.58%) and
      reproducibility (CV=2.57%) was shown. The results of X- and Y-sorted semen
      samples analysed by real time PCR and by flow cytometric reanalysis showed no
      significant difference (P>0.05). The evaluation of X-chromosome bearing sperms
      content in unsorted samples showed an average of 51.11+/-0.56% for ejaculates and
      50.17+/-0.58% for the commercial semen. This new method for quantification of the
      sexual chromosome content in spermatozoa demonstrated to be rapid and reliable,
      providing a valid support to the sperm sexing technologies.

PMID- 16956657
TI  - Is metaphor special?

PMID- 16956658
TI  - Agent Orange, prostate cancer irradiation and acute promyelocyic leukemia (APL):
      is there a link?

PMID- 16956659
TI  - Chronic myelomonocytic leukemia with overlap dysplastic/proliferative
      presentation.

PMID- 16956660
TI  - Expressions of the VLA-4, LFA-1 and Mac-1 integrins in eosinophil migration in a
      case of chronic eosinophilic leukaemia.
AB  - Migration of eosinophil (Eo) into tissues is a hallmark of chronic eosinophilic
      leukaemia (CEL), but the exact mechanism involved in cell migration is unknown.
      We report on a patient with CEL who presented high expressions of VLA-4, LFA-1
      and Mac-1 integrins on the Eo surface, increased chemotaxis of Eo to eotaxin,
      decreased chemotaxis of Eo after inhibition of the cyclic guanosine monophosphate
      (cGMP), and a high level of intracellular cGMP. These findings suggest that an
      upregulation of expression of these integrins on Eo surface and a high
      intracellular level of cGMP may be involved in the increased Eo migration
      observed in our CEL patient. However, the definitive roles of these molecules in
      the proliferation and migration of Eo in CEL disease require wider confirmation
      by analysis of additional patients with the disease.

PMID- 16956661
TI  - Early adversity and alcohol availability persistently modify serotonin and
      hypothalamic-pituitary-adrenal-axis metabolism and related behavior: what
      experimental research on rodents and primates can tell us.
AB  - Early experiences have profound influences on individual developmental
      trajectories. For example alcohol exposure during central nervous system
      development relates to a number of pathological consequences in adulthood. An
      increased risk of developing psychiatric disorders, like major depression and
      impulse-control-related pathologies is associated with alcohol exposure during
      fetal life and/or during adolescence. Additionally, adverse life experiences
      occurring early in development may exacerbate these consequences, while impinging
      on the same neural systems affected by precocious alcohol exposure. Conversely, a
      protective and/or stimulating environment may mitigate these alcohol-related
      negative outcomes. Experimental research in animal models constitutes a primary
      source of information in understanding both functional and dysfunctional human
      adaptations to these events. In this review, a selection of rodent and primate
      studies shows that developmental ethanol exposure on the one hand, and
      environmental treatments aimed at modifying the mother-offspring interaction on
      the other hand, independently modulate similar neuro-endocrine systems. In
      particular, we discuss the effects that the above-mentioned independent variables
      exert on the hypothalamic-pituitary-adrenal (HPA)-axis and on brain serotonergic
      pathways. Experimental evidence indicates that pathological adaptations of these
      systems are valuable predictors of human neuro-behavioral abnormalities like
      depression, impaired impulse control and alcohol abuse. Finally, a working
      hypothesis is proposed, which combines primate and rodent studies aimed: (i) at
      studying functional and pathological individual development following early
      ethanol consumption, and (ii) at heading towards a better definition of potential
      intervention strategies.

PMID- 16956662
TI  - The evaluation of early embryonic neurogenesis after exposure to the genotoxic
      agent 5-bromo-2'-deoxyuridine in mice.
AB  - Developmental neurotoxicity (DNT) is an important issue in children's health.
      Neurogenesis occurs throughout the early fetal to the postnatal period. The
      proliferation of embryonic stem cells can be a target for toxicants, especially
      genotoxic compounds. 5-Bromo-2'-deoxyuridine (BrdU), a thymidine analogue, has
      been used as a marker for proliferating cells. However, we reported that prenatal
      BrdU exposure induced behavioral abnormalities such as hyperactivity in rat and
      mouse offspring. In this study, to further clarify the toxic effect of BrdU on
      the early neurogenesis and to examine the usefulness of the evaluation of this
      process in DNT, C57BL/6 mice were exposed to 100 mg/kg of BrdU once on
      gestational day (GD) 9 or 11, and serial sections from a wide variety of areas of
      the embryonic brains 24 h after the exposure were examined. BrdU exposure on GD11
      induced cell death in some specific areas, such as the neocortex and striatum,
      but not in the substantia nigra, raphe and pons, even though BrdU was
      incorporated into those cells. BrdU decreased the number of cells positive for
      phosphorylated histone 3 (phospho-histone 3), a marker for proliferating cells at
      metaphase of mitosis, in the cortex, mammillary body and cerebellum, suggesting
      that BrdU affected the proliferation of neural stem cells. Exposure on GD9 did
      not induce cell death in the fetal brain. These results indicate that BrdU
      actually impaired the early neurogenesis, supporting the postnatal results, and
      demonstrated that embryonic neurogenesis has heterogeneous sensitivity to the
      genotoxic agents BrdU that differs according to the area and developmental stage.
      The evaluation of events in early neurogenesis such as the proliferation of
      neural stem cells shortly after chemical exposure will be one of the valuable
      endpoints for studying postnatal neurodevelopmental disorders.

PMID- 16956663
TI  - Protective activities of Vaccinium antioxidants with potential relevance to
      mitochondrial dysfunction and neurotoxicity.
AB  - Both the neurotransmitter dopamine (DA) and a neurotoxic metabolite, 6-hydroxy
      DA, can be oxidized to generate hydrogen peroxide and other reactive species
      (ROS). ROS promote oxidative stress and have been implicated in dopaminergic
      neurodegeneration, e.g., Parkinson's disease (PD). There is also evidence for a
      relation between catecholamine-mediated oxidative damage in dopaminergic neurons
      and the effects of these neurotransmitters on the redox state of cytochrome c
      (Cytc). In neurons and other cells, oxidative stress may be enhanced by abnormal
      release of Cytc and other mitochondrial proteins into the cytoplasm. Cytc release
      can result in apoptosis; but sub-apoptogenic-threshold release can also occur,
      and may be highly damaging in the presence of DA metabolites. Loss of
      mitochondrial membrane integrity, a pathological situation of relevance to
      several aging-related neurodegenerative disorders including PD, contributes to
      release of Cytc; and the level of such release is known to be indicative of the
      extent of mitochondrial dysfunction. In this context, we have used a Cytc
      enhanced 6-hydroxy DA oxidation reaction to gauge dietary antioxidant activities.
      Anthocyanin-rich preparations of Vaccinium species (Vaccinium myrtillus,
      Vaccinium corymbosum, and Vaccinium oxycoccus) as well as a purified glycosylated
      anthocyanidin were compared. The most potent inhibition of oxidation was observed
      with V. myrtillus preparation: 50% inhibition with 7 microM of total
      anthocyanins. This activity was 1.5-4 times higher than that for the other
      preparations or for the purified anthocyanin. Ascorbate (Vitamin C), at up to 4
      fold higher concentrations, did not result in significant inhibition in this
      assay. Antioxidant activity in the assay correlated strongly (r2>0.91, P<0.01)
      with reported Vaccinium content of anthocyanins and total cyanidins, but not
      quercetin or myricetin. The results provide evidence for the high potency of
      anthocyanins towards a potentially neurotoxic reaction, and provide a basis for
      in vivo testing of these flavonoids and their physiological metabolites in the
      context of neuro- and mitochondrio-protective effects.

PMID- 16956664
TI  - Inhibition of the oxidative metabolism of 3,4-dihydroxyphenylacetaldehyde, a
      reactive intermediate of dopamine metabolism, by 4-hydroxy-2-nonenal.
AB  - Recent evidence indicates a role for oxidative stress and resulting products,
      e.g. 4-hydroxy-2-nonenal (4HNE) in the pathogenesis of Parkinson's disease (PD).
      4HNE is a known inhibitor of mitochondrial aldehyde dehydrogenase (ALDH2), an
      enzyme very important to the dopamine (DA) metabolic pathway. DA undergoes
      monoamine oxidase-catalyzed oxidative deamination to 3,4
      dihydroxyphenylacetaldehyde (DOPAL), which is metabolized primarily to 3,4
      dihydroxyphenylacetic acid (DOPAC) via ALDH2. The biotransformation of DOPAL is
      critical as previous studies have demonstrated this DA-derived aldehyde to be a
      reactive electrophile and toxic to dopaminergic cells. Therefore, 4HNE produced
      via oxidative stress may inhibit ALDH2-mediated oxidation of the endogenous
      neurotoxin DOPAL. To test this hypothesis, ALDH2 in various model systems was
      treated with 4HNE and activity toward DOPAL measured. Incubation of human
      recombinant ALDH2 with 4HNE (1.5-30 microM) yielded inhibition of activity toward
      DOPAL. Furthermore, ALDH2 in rat brain mitochondrial lysate as well as isolated
      rat brain mitochondria was also sensitive to the lipid peroxidation product at
      low micromolar, as evident by a decrease in the rate of DOPAL to DOPAC conversion
      measured using HPLC. Taken together, these data indicate that 4HNE at low
      micromolar inhibits mitochondrial biotransformation of DOPAL to DOPAC, and
      generation of the lipid peroxidation product may represent a mechanism yielding
      aberrant levels of DOPAL, thus linking oxidative stress to the uncontrolled
      production of an endogenous neurotoxin relevant to PD.

PMID- 16956665
TI  - Indications for antidepressant drug prescribing in general practice in the
      Netherlands.
AB  - BACKGROUND: The intensity of the use of antidepressants in large populations can
      nowadays relatively easily be estimated using databases encompassing prescription
      data. There are shortcomings when using prescription databases as they contain no
      clinical data on patient illness. Antidepressants are prescribed for different
      illnesses, thus information on the indications could help when interpreting
      results from database studies on antidepressant drug use. The aim of this study
      is to investigate for which indications antidepressants are being prescribed in
      general practice in the Netherlands. METHODS: Data were obtained from the Second
      Dutch National Survey of General Practice, carried out by NIVEL (N=385,461).
      Patients, 18 years and older, who received an antidepressant prescription from a
      general practitioner in 2001 were selected (N=13,835). Indications for
      antidepressant drug prescribing were identified using time windows of different
      lengths. RESULTS: Antidepressants are most often being prescribed for depression
      (45.5%) and anxiety/panic disorders (17.2%). For these indications lengthening
      the time window around prescription date from 0 to 180 days resulted in an
      increase of 20-40% in antidepressant drug users identified with these
      indications. LIMITATION: None of our selected indications could be identified in
      the physician-patient contact file for about a third of the antidepressant drug
      users. The study was performed in a general practice setting and did not include
      antidepressant users who consult psychiatrists. CONCLUSION: GPs prescribe
      antidepressants predominantly for treating depression. However, using
      antidepressant drug as a proxy for identifying depressed patients in a
      prescription database should be done with caution and when possible in
      combination with clinical data.

PMID- 16956666
TI  - Distribution of simian immunodeficiency virus target cells in vaginal tissues of
      normal rhesus macaques: implications for virus transmission.
AB  - Most new cases of HIV-1 infection occur as the result of vaginal transmission.
      Identifying the phenotype and distribution of potential viral target cells in the
      vagina is important for understanding events in viral transmission and for
      developing effective prevention strategies. For example, compounds that prevent
      CD4 or CCR5 binding have been demonstrated recently to prevent vaginal
      transmission in rhesus macaques, but the expression and distribution of CCR5 has
      not been examined in the macaque vagina. The objective of this study was to
      examine the distribution and phenotype of cells and molecules in the vagina of
      rhesus macaques that may be involved in HIV transmission, including CCR5, CD3,
      CD4, CD8, CD1a, CD28, CD95, CD123 and HLA-DR. Normal juvenile and adult female
      rhesus macaques were examined by multicolor immunohistochemistry and flow
      cytometry. Although both CD4 and CCR5 were observed in the lamina propria,
      essentially no CD4 or CCR5 expression was detected within the squamous or
      keratinized layers of the vaginal epithelium. CCR5 expression was higher in the
      vaginal lamina propria of mature macaques compared to 1-3-year-old juveniles. The
      vast majority of CD4(+)CCR5(+) lymphocytes in the vagina had a central memory
      (CD95(+)CD28(+)) phenotype. Numerous CCR5-expressing dendritic cells (CD123(+))
      or macrophages (CD68(+)) were observed in the lamina propria, but no CCR5, CD4 or
      DC-SIGN expression was detectable in the epithelium. Thus, the multiple layers of
      squamous epithelium normally covering the vaginal mucosa may provide an effective
      barrier against vaginal HIV-1 transmission. Microbicides that block CD4 or CCR5
      expression may act within the deeper layers of the vaginal epithelium rather than
      on the epithelial surface.

PMID- 16956667
TI  - Cytokine and antibody subclass responses in the intestinal lymph of sheep during
      repeated experimental infections with the nematode parasite Trichostrongylus
      colubriformis.
AB  - The expression of interleukin (IL)-4, IL-5, IL-10, IL-13, TNF-alpha and IFN-gamma
      genes, and parasite-specific IgM, IgG1, IgG2, IgA and total IgE levels, were
      monitored daily in intestinal lymph of sheep infected repeatedly with the
      nematode parasite Trichostrongylus colubriformis. Host genotype had a significant
      influence on IL-13 gene activity, with resistant-line (R) sheep consistently
      expressing higher levels of mRNA than susceptible-line (S) sheep. Mean gene
      expression of IL-13, IL-4 and IFN-gamma did not differ significantly between the
      first and second nematode challenge. Field-primed R and S as well as field-primed
      R and naive S sheep had lower mean gene expression of IL-5 and IL-10,
      respectively, during the second when compared to primary challenge. Genes for IL
      13 and IL-5 were transiently and strongly up-regulated after nematode infection,
      particularly in animals with previous exposure to nematodes. Genes for TNF-alpha
      and IFN-gamma were also transiently up-regulated, but to a lesser extent and more
      typically after primary challenge. Naive sheep of both genotypes produced
      relatively little antibody response after primary challenge. A second nematode
      challenge resulted in large increases in the lymphatic levels of all antibody sub
      classes which were significant for adult antigen-specific IgA and larval antigen
      specific IgG1. In naive S line sheep, the larval-specific IgA and IgG2 response
      appeared delayed when compared to the R line animals. Field-primed R and S line
      sheep had relatively high lymphatic IgG1 levels prior to experimental infection
      and these did not change significantly afterwards. These results demonstrate that
      during nematode infections, the intestinal micro-environment of sheep is
      transiently skewed towards Th2 cytokine dominance, although IFN-gamma gene
      expression continues. This response is accompanied by increases of nematode
      specific IgG1, IgA, IgG2 and IgM, as well as of total IgE in lymph plasma.

PMID- 16956668
TI  - Molecular cloning of multiple forms of the ovine B7-2 (CD86) costimulatory
      molecule.
AB  - To facilitate analysis of the role of costimulatory molecules in the ovine immune
      system, we cloned and sequenced eight putative alternatively spliced transcripts
      of the sheep CD86 (B7-2) costimulatory molecule. Using RT-PCR and rapid
      amplification of cDNA ends (RACE), we cloned the sheep CD86 (B7-2) molecule that
      encodes eight forms, which differ in the length of the signal peptide, the
      presence or absence of a transmembrane region and in their cytoplasmic tails.
      Comparison of the deduced amino acid sequence of the largest ovine CD86 TM form
      (CD86-2) with the sequence of cattle, pig, human and mouse CD86 indicated that
      the deduced protein had a higher degree of similarity to cattle (85% of amino
      acid identity) than to pig (77%), human (59%), and mouse sequence (45% of
      identity). Our results indicate that mRNA transcripts encoding different CD86
      protein forms are expressed in sheep, like in other mammals, and suggest that the
      expression of this gene may be regulated at the transcriptional or RNA splicing
      level, which could give rise to tissue-specific expression of CD86. It is
      possible that, in the sheep, these CD86 mRNA variants could play different
      regulatory roles in T cell activation.

PMID- 16956669
TI  - Quantitation of immune response gene expression and cellular localisation of
      interleukin-1beta mRNA in Atlantic salmon, Salmo salar L., affected by amoebic
      gill disease (AGD).
AB  - The characterisation of selected immune response genes during amoebic gill
      disease (AGD) in Atlantic salmon, Salmo salar L., was performed using semi
      quantitative RT-PCR, quantitative real-time RT-PCR (qRT-PCR), and in situ
      hybridisation (ISH). The immune response genes of interest were interleukin-1beta
      (IL-1beta), inducible nitric oxide synthase (iNOS), serum amyloid A (SAA), and
      serum amyloid P-like pentraxin (SAP). Atlantic salmon were inoculated with the
      ectoparasite Neoparamoeba sp., the causative agent of AGD, and gill, liver and
      anterior kidney tissue sampled at 0, 7 and 14 d post-inoculation (p.i.). Semi
      quantitative RT-PCR was performed on the tissue samples to identify up/down
      regulated mRNA expression relative to uninfected control fish and normalised to
      the housekeeping gene, beta-actin. Interleukin-1beta (IL-1beta) was the only
      immune response gene of those investigated whose mRNA was differentially
      regulated in any of the tissues and was found to be up-regulated in the gills by
      semi-quantitative RT-PCR. Increased gill IL-1beta mRNA expression was then
      accurately quantitated and confirmed using probe-based qRT-PCR. The cellular
      localisation of the IL-1beta mRNA expression in the gills of uninfected and
      infected fish was then determined by ISH using an IL-1beta-specific biotinylated
      cRNA probe. Expression of IL-1beta mRNA was localised to filament and lamellar
      epithelium pavement cells in gills of uninfected and infected Atlantic salmon.
      These data implicate the involvement of IL-1beta at the site of infection, the
      gills, of Atlantic salmon during AGD. This work supports previous studies that
      suggest IL-1beta is important in the regulation of the fish immune response to
      parasitic infection but additionally shows the cellular localisation of fish IL
      1beta mRNA expression during infection.

PMID- 16956670
TI  - Reduced cytokine-mediated up-regulation of HLA-DR in TAP-deficient fibroblasts.
AB  - Human deficiency in transporter associated with antigen processing (TAP) is
      characterized by a very low surface expression of human leukocyte antigen (HLA)
      class I molecules in hematopoietic and non hematopoietic cells. Among the latter,
      TAP-deficient skin fibroblasts have previously been shown by us to be very
      sensitive to lysis by activated autologous NK cells, even in the presence of
      cytokines that up-regulate HLA class I expression, a mechanism sufficient to
      protect normal fibroblasts from NK cell-mediated killing. Our complementary
      investigations on two TAP-deficient skin fibroblast cell lines surprisingly
      revealed that in response to proinflammatory cytokines, up-regulation of HLA-DR
      molecules at the cell surface is much less marked than in the case of normal skin
      fibroblasts. In contrast, the surface molecules CD40 and CD54 increase as much as
      observed on normal cells, suggesting that TAP-deficient fibroblasts are able to
      efficiently transduce cytokine-mediated stimulating signals. Transfection of an
      intact TAP gene into one of the TAP-deficient fibroblast cell lines restored a
      normal HLA class I expression that strongly increased upon IFN-gamma-mediated
      stimulation, whereas HLA-DR still remained lower than in control cells. These
      results suggest that, in addition to the defect in the HLA class I antigen
      presentation pathway, HLA-DR up-regulation is affected in TAP-deficient skin
      fibroblasts through an unknown mechanism probably independent from TAP.

PMID- 16956671
TI  - Fanconi anemia (FA) and squamous cell carcinoma in childhood.

PMID- 16956672
TI  - Detection of beta-herpesviruses in allogenic stem cell recipients by quantitative
      real-time PCR.
AB  - The aim of this study was to investigate the clinical impact of reactivation of
      human herpes virus-6 (HHV-6) and HHV-7 infections in stem cell transplantation
      recipients, and to examine a possible increase in virulence of the two
      roseoloviruses when a reactivation of CMV (HHV-5) simultaneously occurs. For this
      purpose, quantitative real-time PCR systems were developed to assess the viral
      load of CMV, HHV-6, or HHV-7 in the plasma of haematopoetic stem cell recipients.
      One hundred and ninety-eight plasma samples from 37 patients who underwent
      allogeneic stem cell transplantation were tested for CMV, HHV-6, and HHV-7 by a
      5'-exonuclease (TaqMan) quantitative real-time PCR. The CMV load obtained by the
      real-time PCR assay was compared retrospectively with results generated
      previously with a commercially available test (COBAS AMPLICOR CMV MONITOR Test,
      Roche). The results suggest that CMV and HHV-6 may be associated with post
      transplantation end-organ disease, while HHV-7 reactivation had no impact on the
      patients included in this study. No evidence for a potential interaction of the
      roseoloviruses and CMV infections was found.

PMID- 16956673
TI  - PCR-based detection is unable to consistently distinguish HIV 1LTR circles.
AB  - Quantitative PCR methods are routinely used to measure multiple HIV cDNA forms,
      including linear cDNA, early and late reverse transcripts, 2LTR circles, and
      integrated provirus. PCR-based methods for the detection of 1LTR circles have
      been proposed, but are complicated by the inherent homology of the LTR sequence
      present in all cDNA forms. Amplicons with variable lengths of homology showed
      that it is difficult to discriminate 1LTR circles faithfully from other cDNA
      forms. Addition of formamide, DMSO, or glycerol did not eliminate amplification
      of spurious products. Thus, detection of 1LTR circles by PCR is not reliable.

PMID- 16956674
TI  - Exciting inhibition in psychostimulant addiction.
AB  - Neuroplasticity induced in the nucleus accumbens by repeated psychostimulant
      administration is thought to underlie the vulnerability to relapse in addicts.
      Electrophysiological research presents a contradictory portrait of
      psychostimulant-induced neuroplasticity, reflecting both increases and decreases
      in excitatory transmission. Drug-induced adaptations of ionic conductances
      decrease the intrinsic excitability of individual nucleus accumbens spiny neurons
      but, in the context of the circuitry in which these neurons are embedded, such
      reduced intrinsic excitability increases the salience of excitatory drive that is
      elicited by drug-associated stimuli. Thus, we propose that reduced basal
      excitability, combined with enhanced excitatory drive by drug-associated stimuli,
      contributes to the two cardinal features of addiction: reduced responding to
      natural reward and enduring vulnerability to relapse.

PMID- 16956675
TI  - Assessing sensory function in locomotor systems using neuro-mechanical
      simulations.
AB  - Computer simulations are being used increasingly to gain an understanding of the
      complex interactions between the neuronal, sensory, muscular and mechanical
      components of locomotor systems. Recent neuro-mechanical simulations of walking
      in humans, cats and insects, and of swimming in lampreys, have provided new
      information on the functional role of specific groups of sensory receptors in
      regulating locomotion. As we discuss in this review, these studies also make it
      clear that a full understanding of the neural and mechanical mechanisms that
      underlie locomotion can be achieved only by using simulations in parallel with
      physiological investigations. The widespread implementation of this approach
      would be enhanced by the development of freely available and easy-to-use software
      tools.

PMID- 16956676
TI  - Prenatal dexamethasone exposure, postnatal development, and adulthood prepulse
      inhibition and latent inhibition in Wistar rats.
AB  - Prenatal stress is an important risk factor in schizophrenia, and the
      aetiological factors mediating this relationship are central to the
      neurodevelopmental hypothesis of schizophrenia. The glucocorticoid receptor (GR)
      agonist dexamethasone (DEX) is commonly prescribed for prenatal conditions, and
      results in GR activation, which is part of the stress response. To investigate
      animal evidence for whether prenatal DEX leads to development of schizophrenia
      like phenotypes, Wistar rats were prenatally exposed to DEX (0.1mg/kg/day)
      between the gestational days 15 and 21, and tested in two paradigms known to be
      disrupted in schizophrenia patients: prepulse inhibition (PPI) and latent
      inhibition (LI). A cross-fostering design was used to allow dissociation of any
      direct prenatal effects on offspring from effects dependent on DEX exposure of
      the rearing dam. Pup birth weight was reduced by prenatal DEX treatment. DEX
      treated dams demonstrated increased pup-directed behaviour. There were additive
      effects of prenatal DEX treatment and DEX treatment of rearing dam in terms of
      reduced body weight in adulthood. In one of two replications, PPI was increased
      by prenatal DEX in males only and specific to the highest prepulse intensity.
      There was no evidence that LI was disrupted by prenatal DEX treatment. This study
      does not provide support for the hypothesis that prenatal DEX exposure leads to
      schizophrenia-like deficits in PPI or LI, suggesting that GR prenatal programming
      is not a mechanism of direct relevance to the neurodevelopmental hypothesis of
      schizophrenia.

PMID- 16956677
TI  - Precise rhythmicity in activity of neocortical, thalamic and brain stem neurons
      in behaving cats and rabbits.
AB  - Rhythmic discharges of neurons are believed to be involved in information
      processing in both sensory and motor systems. However their fine structure and
      functional role need further elucidation. We employed a pattern-based approach to
      search for episodes of precisely rhythmic activity of single neurons recorded in
      different brain structures in behaving cats and rabbits. We defined discharge
      patterns using an algorithmic description, which is different from the previously
      suggested template methods. We detected episodes of precisely rhythmic
      discharges, specifically, triads of constant (precision +/-2.5%) inter-spike
      intervals in the 10-70 ms range. In 54% (67/125) of neurons tested, these
      patterns could not be explained by random occurrences or by steady or slowly
      changing input. Rhythmic patterns occurred at a wide range of inter-spike
      intervals, and were imbedded in non-rhythmic activity. In many neurons, timing of
      these precisely rhythmic patterns was related to different locomotion tasks or to
      respiration.

PMID- 16956678
TI  - Skilled reaching impairments follow intrastriatal hemorrhagic stroke in rats.
AB  - The infusion of autologous blood into the brain of rats is a widely used model of
      intracerebral hemorrhage (ICH). Careful assessment of functional recovery is an
      essential part of preclinical testing (e.g., putative cytoprotectants). However,
      few tests detect long-term deficits in this model. In this study, we used the
      staircase and single pellet tests to characterize skilled reaching ability after
      striatal ICH. Rats were trained to reach for food pellets in these tasks before
      ICH, which was created by infusing 100muL of autologous blood into the striatum.
      We assessed reaching success in both tasks for 5 days starting 7 and 28 days
      after ICH. We counted the number of reaching attempts made with each forelimb in
      the staircase task and performed kinematic analysis of reaching in the single
      pellet task. The contralateral (to lesion) forelimb reaching success was
      significantly impaired in the staircase task 1 week after ICH, but this recovered
      to pre-surgical levels thereafter. Reaching deficits in the single pellet task
      were more severe and persistent. Detailed analysis of reaches on day 11 revealed
      several abnormalities in the following movement components: pronation, grasping,
      supinating the paw and releasing the pellet. At 1 month, only digit opening and
      supination were impaired. Accordingly, the single pellet task is better at
      detecting long-term skilled reaching impairments in the whole blood model of ICH.
      Thus, the single pellet task seems suited to cytoprotection and rehabilitation
      studies.

PMID- 16956679
TI  - Swimming performance and energy metabolism of rainbow trout, common carp and
      gibel carp respond differently to sublethal copper exposure.
AB  - We compared the effects of sublethal waterborne copper exposure on swimming
      performance and respiration rates in rainbow trout, Oncorhynchus mykiss, with
      those in less sensitive cyprinid species such as common carp, Cyprinus carpio,
      and gibel carp, Carassius auratus gibelio. These cyprinids are considerably more
      resistant to Cu intoxication, and differ from trout in swimming performance and
      respiratory behaviour. Critical swimming speed (U(crit)), oxygen consumption,
      plasma ammonia and muscle ammonia, lactate and pH were measured during a 28-day
      sublethal exposure to 1 microM Cu. U(crit) decreased with 48, 31 and 13% within
      the first 12-24 h for rainbow trout, common and gibel respectively. Gibel carp
      recovered quickly and experienced no further reduction in swimming performance.
      Recovery of swimming capacity in rainbow trout and common carp was only partial.
      All three species displayed similar plasma ammonia peaks in the first hours to
      days, and a more gradual muscle ammonia accumulation over time. Whereas no signs
      of respiratory stress occurred in rainbow trout, common carp experienced a
      transient reduction in oxygen consumption combined with anaerobic metabolism
      after 24 h of exposure. At the same time, oxygen consumption was also reduced in
      gibel carp, but no signs of anaerobic metabolism were detected. Cu accumulated
      quickly to similar levels (36-39 microg g(-1) dry weight at day 3) in the gills
      of all three species, after which accumulation leveled off. Liver tissue of
      rainbow trout had a high Cu level from the start, and Cu concentration did not
      show any additional accumulation. In contrast, common carp liver showed a
      significant Cu accumulation from day 3 onwards, while accumulation in gibel
      livers was much slower and was significant from day 7 onwards. Interestingly, Cu
      accumulation patterns in plasma and kidney revealed a possibly important role for
      the kidney in Cu homeostasis of gibel carp.

PMID- 16956680
TI  - Health inequality and non-monotonicity of the health related social welfare
      function.
AB  - In a recent paper in this journal Abasolo and Tsuchiya [Abasolo, I., Tsuchiya,
      A., 2004. Exploring social welfare functions and violation of monotonicity: an
      example from inequalities in health. Journal of Health Economics 23, 313-329]
      have strongly argued for the use of a non-monotonic health related social welfare
      function. This note discusses both the limitations of the measure proposed by
      Abasolo and Tsuchiya [Abasolo, I., Tsuchiya, A., 2004. Exploring social welfare
      functions and violation of monotonicity: an example from inequalities in health.
      Journal of Health Economics 23, 313-329] and the problems associated with their
      empirics. We are able to show how non-monotonicity may lead to paradoxical
      results and policies. Further we examine the empirics of Abasolo and Tsuchiya
      [Abasolo, I., Tsuchiya, A., 2004. Exploring social welfare functions and
      violation of monotonicity: an example from inequalities in health. Journal of
      Health Economics 23, 313-329] and provide an alternative explanation to the
      observed patterns in the data that do not violate monotonicity. Finally we
      briefly mention why the Atkinson-Sen framework may be more appropriate as a way
      forward.

PMID- 16956681
TI  - Advances in cereal genomics and applications in crop breeding.
AB  - Recent advances in cereal genomics have made it possible to analyse the
      architecture of cereal genomes and their expressed components, leading to an
      increase in our knowledge of the genes that are linked to key agronomically
      important traits. These studies have used molecular genetic mapping of
      quantitative trait loci (QTL) of several complex traits that are important in
      breeding. The identification and molecular cloning of genes underlying QTLs
      offers the possibility to examine the naturally occurring allelic variation for
      respective complex traits. Novel alleles, identified by functional genomics or
      haplotype analysis, can enrich the genetic basis of cultivated crops to improve
      productivity. Advances made in cereal genomics research in recent years thus
      offer the opportunities to enhance the prediction of phenotypes from genotypes
      for cereal breeding.

PMID- 16956682
TI  - A separated primary and scatter model for independent dose calculation of
      intensity modulated radiotherapy.
AB  - BACKGROUND AND PURPOSE: Independent checking of beam monitor units is an
      essential step in the preparation of any radiotherapy plan. The present work
      describes a simple model for calculating a point dose from an arbitrary number of
      irregular, asymmetric fields, typical of beam segments used for IMRT. MATERIALS
      AND METHODS: Primary and scatter dose contributions were separated using a two
      parameter exponential fit to measured beam data, from which differential scatter
      is determined. A total of 60 IMRT patient plans for a five-field prostate class
      solution were investigated to validate the model. RESULTS: The average difference
      between the model's prediction and direct measurement of reference dose was found
      to be -0.6% (ranging from -2.9% to +1.6%), with a standard deviation of 1.0%.
      This compares well with the observed average difference between treatment
      planning system prediction and direct measurement of +0.8% (SD 0.6%).
      CONCLUSIONS: The model is shown to provide a reliable and accurate independent
      check of planning system monitor units for the prostate IMRT plans studied.
      Implementation of the model could significantly reduce the time needed for point
      dose verification of IMRT plans currently performed by direct measurement.

PMID- 16956683
TI  - Pimonidazole labelling and response to fractionated irradiation of five human
      squamous cell carcinoma (hSCC) lines in nude mice: the need for a multivariate
      approach in biomarker studies.
AB  - OBJECTIVE: To investigate the influence on local control after fractionated
      radiotherapy of hypoxia measured in unirradiated tumours using the hypoxic marker
      Pimonidazole, using multivariate approaches. MATERIAL AND METHODS: Five human
      squamous cell carcinoma lines (FaDu, UT-SCC-15, UT-SCC-14, XF354, and UT-SCC-5)
      were transplanted subcutaneously into the right hind-leg of NMRI nude mice.
      Histological material was collected from 60 unirradiated tumours after injection
      of Pimonidazole. The relative hypoxic area within the viable tumour area
      (Pimonidazole hypoxic fraction, pHF) was determined in seven serial 10 microm
      cross-sections per tumour by fluorescence microscopy and computerized image
      analysis. Local tumour control was evaluated in a total of 399 irradiated tumours
      at 120 days after 30 fractions given within 6 weeks with total doses between 30
      and 115 Gy. RESULTS: Tumour lines showed pronounced heterogeneity in both pHF and
      TCD50. Mean pHF values varied between 5% and 37%, TCD50 values between 47 and 130
      Gy. A Cox Proportional Hazards model of time to recurrence with two covariates,
      dose and pHF, yielded significant contributions of both parameters on local
      control (p < 0.005) but violated the proportional hazards assumption, suggesting
      that other factors also influence tumour control. Introduction of histological
      grade as an example of a confounding factor into the model improved the fit
      significantly. Local control rates decreased with increasing pHF and this effect
      was more pronounced at higher doses. CONCLUSIONS: This study confirms that tumour
      hypoxia measured using Pimonidazole in untreated tumours is a significant
      determinant of local control after fractionated irradiation. The data support the
      use of multivariate approaches for the evaluation of a single prognostic
      biomarker such as Pimonidazole, and more generally, suggest that they are
      required to establish accurate prognostic factors for tumour response.

PMID- 16956684
TI  - Whole brain irradiation following surgery or radiosurgery for solitary brain
      metastases: mature results of a prematurely closed randomized Trans-Tasman
      Radiation Oncology Group trial (TROG 98.05).
AB  - We evaluated the effect of adjuvant whole brain irradiation (WBI) after surgery
      or radiosurgery for solitary brain metastases in a Phase III multicentre trial
      with randomization to 30-36 Gy WBI or observation. The study was closed early due
      to slow accrual after 19 patients (WBI 10, observation 9). There was no
      difference in CNS failure-free survival or overall survival between the arms.
      There was a trend to reduced CNS relapse with WBI (30% versus 78%, P=0.12).
      Limited analysis of quality of life and neurocognitive function data revealed no
      evidence of difference between the arms. Our results are not inconsistent with
      two larger randomized trials and support the use of upfront WBI to decrease brain
      recurrence in this setting.

PMID- 16956685
TI  - Gamma amplitudes are coupled to theta phase in human EEG during visual
      perception.
AB  - Human subjects typically keep about seven items (plus or minus two) in short-term
      memory (STM). A theoretical neuronal model has been proposed to explain this
      phenomenon with physiological parameters of brain oscillations in the gamma and
      theta frequency range, i.e., roughly 30-80 and 4-8 Hz, respectively. In that
      model, STM capacity equals the number of gamma cycles (e.g., 25 ms for 40 Hz),
      which fit into one theta cycle (e.g., 166 ms for 6 Hz). The model is based on two
      assumptions: (1) theta activity should modulate gamma activity; and (2) the
      theta/gamma ratio should correlate with human STM capacity. The first assumption
      is supported by electrophysiological data showing that the amplitude of gamma
      oscillations is modulated by the phase of theta activity. However, so far, this
      has only been demonstrated for intracranial recordings. We analyzed human event
      related EEG oscillations recorded in a memory experiment in which 13 subjects
      perceived known and unknown visual stimuli. The paradigm revealed event-related
      oscillations in the gamma range, which depended significantly on the phase of
      simultaneous theta activity. Our data are the first scalp-recorded human EEG
      recordings revealing a relationship between the gamma amplitude and the phase of
      theta oscillations, supporting the first assumption of the above-mentioned
      theory. Interestingly, the involved frequencies revealed a 7:1 ratio. However,
      this ratio does not necessarily determine human STM capacity. Since such a
      correlation was not explicitly tested in our paradigm, our data are not
      conclusive about the second assumption. Instead of theta phase modulating gamma
      amplitude, it is also conceivable that focal gamma activity needs to be
      downsampled to theta activity, before it can interact with more distant brain
      regions.

PMID- 16956687
TI  - Pre-fractionation of archival frozen tumours for proteomics applications.
AB  - We report a protocol for pre-fractionation of proteins from frozen tumours. Using
      this protocol two separate protein fractions are extracted: Fraction 1 is
      enriched for cytosolic and Fraction 2 for nuclear/nuclear membrane proteins. The
      accuracy and reproducibility of the protocol were demonstrated by Western blot
      analyses and SELDI-TOF-MS profilings. The resulting protein profiles were similar
      within the respective groups of Fractions 1 and 2 samples, without differences
      between freshly prepared tumours or those obtained as frozen tissue from
      biobanks.

PMID- 16956686
TI  - Polyhydroxyalkanoate (PHA) biosynthesis from structurally unrelated carbon
      sources by a newly characterized Bacillus spp.
AB  - A newly acquired polyhydroxyalkanoate (PHA) producing Bacillus spp. was
      identified to be a strain of Bacillus cereus using a range of microbiological and
      molecular techniques. This strain, named B. cereus SPV, was found to be capable
      of using a wide range of carbon sources including glucose, fructose, sucrose,
      various fatty acids and gluconate for the production of PHAs, an advantage for
      the commercial production of the polymers. The media used for the polymer
      production was novel in the context of the genus Bacillus. The PHA, once
      produced, was found to remain at a constant maximal concentration, without any
      degradation, a great advantage for the commercial production of the PHAs. This
      particular strain of Bacillus spp. was able to synthesize various PHAs with 3
      hydroxybutyrate (3HB), 3-hydroxyvalerate (3HV) and 4-hydroxybutyrate (4HB)-like
      monomer units from structurally unrelated carbon sources such as fructose,
      sucrose and gluconate. This is the first report of the incorporation of a 4HB
      related monomer containing PHA by the genus Bacillus and from structurally
      unrelated carbon sources. The PHAs isolated had molecular weights ranging between
      (0.4 and 0.8) x 10(6) and low polydispersity index values (M(W)/M(N)) ranging
      from 2.6 to 3.4.

PMID- 16956688
TI  - The difficult-to-cultivate coxsackieviruses A can productively multiply in
      primary culture of mouse skeletal muscle.
AB  - Coxsackieviruses A (CVA) are associated with several clinical manifestations such
      as aseptic meningitis and paralytic syndromes in humans. Most CVA are difficult
      to-cultivate, which impedes their propagation and isolation from clinical
      material. Here, we tested the ability of cultivable (CVA-13, CVA-14), and
      difficult-to-cultivate (CVA-6, CVA-22) strains to infect primary cultures of
      skeletal muscle cells established from newborn mice. We found that such cultures
      sustained the multiplication of these CVA, as evidenced by the development of a
      cytopathic effect, already in the initial preparation or after passaging once.
      Cultures established for no more than 24h were sensitive to infection whereas
      older preparations were resistant. Using confocal microscopy after double
      immunolabeling of the VP1 capsid protein and the muscle cell marker myosin, we
      demonstrated that only the myoblasts were infected, resulting in VP1 expression
      throughout their cytoplasm. Inoculation of infected cultures to suckling mice
      resulted in paralysis indicating that infection was productive. The nature of
      candidate receptors for virus entry in such cultures and the influence of cell
      culture conditions on the expression of these putative receptors are discussed.
      This work suggests that primary cultures of skeletal muscle cells could be used
      to propagate and isolate any CVA strain.

PMID- 16956689
TI  - In addition to obesity and insulin resistance, microalbuminuria and diminished
      insulin secretion are linked with the metabolic syndrome in community-dwelling
      nondiabetic Taiwanese subjects.
AB  - Although insulin resistance and obesity are currently considered primary factors
      underlying development of the metabolic syndrome, microalbuminuria and inadequate
      insulin secretion may also be involved. The present study is the first to examine
      intercorrelations among these factors in a community-based Taiwanese population.
      An epidemiological survey of chronic diseases conducted in 1996 was utilized to
      evaluate 1340 community-dwelling, nondiabetic adults. Principal component factor
      analyses involving varimax orthogonal rotation of transformed continuously
      distributed variables were performed. Sex-specific factor analyses yielded four
      separate factors in women (obesity/insulin resistance, lipid, blood pressure and
      insulin resistance/secretion factors) and three in men (obesity/insulin
      resistance/secretion, lipid and blood pressure factors). For men the corrected
      insulin response clustered with obesity, and insulin resistance loaded on the
      same factor, explaining 31% of variance; however, microalbuminuria was closely
      linked with blood pressure variables, and the corrected insulin response loaded
      on the same factor, explaining 13.2% of variance. Obesity and insulin resistance
      were confirmed as central anomalies of all features of the metabolic syndrome.
      The observed linkage of impaired beta-cell function and microalbuminuria with the
      metabolic syndrome should facilitate prediction of the onset of cardio-vasculo
      metabolic disorders. Inadequate beta-cell function and microalbuminuria are
      plausible components of the metabolic syndrome in Taiwanese subjects.

PMID- 16956690
TI  - Isoprostanes, a marker of lipid peroxidation, may not be involved in the
      development of glucose intolerance.
AB  - We investigated whether isoprostanes, as a marker of lipid peroxidation, may be
      involved in the development of impaired glucose tolerance (IGT) or diabetes.
      Using a nested case-control study, we tracked the changes in isoprostane levels,
      insulin sensitivity (IS) and beta-cell function (BCF) in Afro-Jamaicans who
      progressed to IGT and diabetes over 3.9 years. Anthropometry, glucose tolerance,
      insulin levels, blood pressure and urinary isoprostane concentration were
      measured at baseline and follow-up. IS and BCF were estimated by the method of
      homeostasis assessment. Fifty-two individuals who progressed to IGT or diabetes
      and 44 age, sex and body mass index (BMI) matched controls were studied.
      Progression to glucose intolerance was significantly related with baseline BCF
      (p< or =0.01), but not isoprostane levels or IS. Glucose concentrations (fasting
      and 2 h) on follow-up were significantly correlated to baseline IS, baseline BCF,
      follow-up IS and follow-up BCF (p-values<0.05). In multiple regression analysis,
      only follow-up IS and BCF (p-values< or =0.001) independently predicted fasting
      glucose and 2h glucose levels at follow-up. Isoprostanes were not significantly
      associated with IS or BCF (p-values>0.1). We concluded that isoprostanes may not
      be causally involved in the development of glucose intolerance, insulin
      resistance or deteriorating BCF.

PMID- 16956691
TI  - Plasma visfatin levels in patients with newly diagnosed and untreated type 2
      diabetes mellitus and impaired glucose tolerance.
AB  - Visfatin, a new adipokine, facilitates adipogenesis and has insulin-mimetic
      properties. We aimed to investigate the plasma visfatin levels in patients with
      newly diagnosed and untreated type 2 diabetes mellitus (T2DM) and impaired
      glucose tolerance (IGT), who had no obesity or hypertension. Twenty-two patients
      with T2DM, 18 subjects with IGT and 40 healthy controls were enrolled. Visfatin
      levels were measured along with the BMI, blood pressure, lipids, glucose,
      insulin, adiponectin and hsCRP levels, and HOMA-IR indexes. Age, sex and BMI were
      similar in all groups. Visfatin levels were higher in the diabetic group than the
      controls (p=0.01). There was no significant difference in the visfatin levels
      between the T2DM and IGT groups as well as IGT group and healthy controls. Plasma
      visfatin concentrations did not differ between men and women. Visfatin levels did
      not correlate with BMI, blood pressure, plasma adiponectin, insulin, hsCRP,
      glucose and lipid levels or HOMA-IR indexes in the three groups. These results
      indicate that hyperglycemia causes an increase in plasma visfatin levels and, as
      in people with T2DM but not with IGT, this increase gets more prominent as the
      glucose intolerance worsens.

PMID- 16956692
TI  - Preheparin serum lipoprotein lipase mass might be a biomarker of metabolic
      syndrome.
AB  - Lipoprotein lipase mass in preheparin serum (preheparin LPL mass) is assumed to
      reflect some of the LPL production in the whole body and insulin sensitivity.
      While metabolic syndrome is a common underlying condition for cardiovascular
      diseases, biological marker of this syndrome has not been fully established. To
      clarify the characteristics of preheparin LPL mass in metabolic syndrome, 362
      Japanese subjects were studied to examine the relationship between symptoms of
      metabolic syndrome and preheparin LPL mass and compare with plasma adiponectin.
      Furthermore the relation with urinary 8-hydroxydeoxyguanosine (8-OHdG) that
      reflects oxidative stress to DNA was also studied. Both preheparin LPL mass and
      plasma adiponectin correlated positively with HDL-cholesterol and negatively with
      body weight and triglyceride. Only preheparin LPL mass showed a negative
      correlation with fasting blood glucose and HbA1c. Both mean preheparin LPL mass
      and plasma adiponectin decreased with an increase in severity of the metabolic
      syndrome with/without obesity and with/without diabetes. The correlation
      coefficient between preheparin LPL mass and plasma adiponectin was r=0.562. A
      negative correlation between preheparin LPL mass and urinary 8-OHdG was observed.
      These results suggest that low preheparin LPL mass may reflect systemic oxidative
      stress and also a biomarker of the severity of metabolic syndrome.

PMID- 16956693
TI  - An audit of standards of care at a Sri Lankan diabetic clinic.

PMID- 16956694
TI  - Clinical predictors versus epidermal growth factor receptor mutation in gefitinib
      treated non-small-cell lung cancer patients.
AB  - BACKGROUND: Clinical predictors including Asian, female, adenocarcinoma and never
      smoker and epidermal growth factor mutation are associated with gefitinib
      responsiveness in non-small-cell lung cancer. Direct comparison between clinical
      predictors and EGFR mutation for their predictive power has not been reported.
      PATIENTS AND METHODS: For 120 Korean NSCLC patients treated with gefitinib, we
      have analyzed EGFR mutational status in exons 18, 19 and 21. Patients were
      grouped according to the number of clinical predictors (female, adenocarcinoma
      and never-smoker). Response rate (RR), time-to-progression (TTP) and overall
      survival (OS) were analyzed. Multivariate analysis was performed to investigate
      which approach yielded better prediction. RESULTS: RRs according to number of
      clinical predictors were 0: 3.4%, 1: 17.1%, 2: 29.4% and 3: 33.3% (p=0.002).
      Patients with gefitinib-sensitive EGFR mutation showed 61.9% RR compared with
      12.1% in the remaining patients (p<0.001). RRs were higher in patients with the
      EGFR mutations regardless of the number of clinical predictors. In multivariate
      analysis, gefitinib-sensitive EGFR mutation showed higher odds ratio of response
      (9.6, 95% confidence interval [CI] 3.2-28.7) compared with number of clinical
      predictors (1.7, 95% CI 1.1-2.7). Hazard ratio (HR) of TTP was also better in
      gefitinib-sensitive EGFR mutation (0.24, 95% CI 0.12-0.47) than number of
      clinical predictors (0.83, 95% CI 0.69-0.99). Only gefitinib-sensitive EGFR
      mutation was associated with improved OS (HR 0.25, 95% CI 0.12-0.52). CONCLUSION:
      EGFR mutation should be analyzed whenever possible for effective prediction of
      objective benefit from gefitinib in NSCLC patients with one or more clinical
      predictors.

PMID- 16956695
TI  - Neurokinin A and neurokinin B in the human retina.
AB  - Very recently, the authors found levels of neurokinin (NK) A-like
      immunoreactivities in the human retina which were more than five times higher
      than those of substance P (SP). The present study aimed to find out how many of
      these immunoreactivities can be attributed to NKA and NKB and then the exact
      distribution pattern of both NKA and NKB was evaluated in the human retina and
      compared with that of SP. For this purpose, NKA-like immunoreactivities were
      characterized in the human retina by reversed phase HPLC followed by
      radioimmunoassay using the K12 antibody which recognizes both NKA and NKB.
      Furthermore, the retinae from both a 22- and 70-year-old donor were processed for
      double-immunofluorescence NKA/SP and NKB/SP. The results showed that NKA
      contributes to approximately two thirds and NKB to approximately one third of the
      immunoreactivities measured with the K12 antibody. NKA was found to be localized
      in sparse amacrine cells in the proximal inner nuclear layer, in displaced
      amacrine cells in the ganglion cell layer with processes ramifying in stratum 3
      of the inner plexiform layer and also in sparse ganglion cells. By contrast,
      staining for NKB was only observed in ganglion cells and in the nerve fiber
      layer. Double-immunofluorescence revealed cellular colocalization of NKA with SP
      and also of NKB with SP. Thus, the levels of NKA and NKB are more than three and
      two times higher than those of SP, respectively. Whereas the distribution pattern
      of NKA is typical for neuropeptides, the localization of NKB exclusively in
      ganglion cells is atypical and unique.

PMID- 16956696
TI  - Hyperammonemia induces transport of taurine and creatine and suppresses claudin
      12 gene expression in brain capillary endothelial cells in vitro.
AB  - Ammonia is a key neurotoxin involved in the neurological complications of acute
      liver failure. The present study was undertaken to study the effects of exposure
      to pathophysiologically relevant concentrations of ammonium chloride on cultured
      brain capillary endothelial cells in order to identify mechanisms by which
      ammonia may alter blood-brain barrier function. Conditionally immortalized mouse
      brain capillary endothelial cells (TM-BBB) were used as an in vitro model of the
      blood-brain barrier. Gene expression of a series of blood-brain barrier
      transporters and tight junction proteins was assessed by quantitative real time
      PCR analysis. Exposure to ammonia (5mM for 72h) resulted in significant increases
      in mRNA levels of taurine transporter (TAUT; 2.0-fold increase) as well as
      creatine transporter (CRT; 1.9-fold increase) whereas claudin-12 mRNA expression
      was significantly reduced to 67.7% of control levels. Furthermore, [(3)H]taurine
      and [(14)C]creatine uptake were concomitantly increased following exposure to
      ammonia, suggesting that up-regulation of both TAUT and CRT under hyperammonemic
      conditions results in an increased function of these two transporters in TM-BBB
      cells. TAUT and CRT are respectively involved in osmoregulation and energy
      buffering in the brain, two systems that are thought to be affected in acute
      liver failure. Furthermore, claudin-12 down-regulation suggests that
      hyperammonemia may also affect tight junction integrity. Our results provide
      evidence that ammonia can alter brain capillary endothelial cell gene expression
      and transporter function. These findings may be relevant to pathological
      situations involving hyperammonemia, such as liver disease.

PMID- 16956697
TI  - Transporter mediated GABA release in the retina: role of excitatory amino acids
      and dopamine.
AB  - In general, the release of neurotransmitters in the central nervous system is
      accomplished by a calcium-dependent process which constitutes a common feature of
      exocytosis, a conserved mechanism for transmitter release in all species.
      However, neurotransmitters can also be released by the reversal of their
      transporters. In the retina, a large portion of GABA is released by this
      mechanism, which is under the control of neuroactive agents, such as excitatory
      amino acids and dopamine. In this review, we will focus on the transporter
      mediated GABA release and the role played by excitatory amino acids and dopamine
      in this process. First, we will discuss the works that used radiolabeled GABA to
      study the outflow of the neurotransmitter and then the works that took into
      consideration the endogenous pool of GABA and the topography of GABAergic
      circuits influenced by excitatory amino acids and dopamine.

PMID- 16956698
TI  - Cocaine-induced oxidative stress precedes cell death in human neuronal progenitor
      cells.
AB  - By 2003, an estimated 34 million Americans had used cocaine according to the
      National Survey on Drug Use & Health. About 5.9 million of those had used in the
      past 12 months. Chronic cocaine users often develop addiction, dependency and
      tolerance to the drug. The psychological and physical effects of cocaine are due
      to the disruption of the limbic system in the central nervous system (CNS).
      Increased oxidative stress reported in the frontal cortex and the striatum of
      rats exposed to cocaine suggests that oxidative damage plays a significant role
      in cocaine-induced disruption of the CNS. Although it is evident that cocaine
      induces oxidative stress in the CNS, little has been learned about whether such
      increased oxidative stress is also relevant to apoptosis in cocaine-exposed
      models. To gain insight into the role of cocaine-induced oxidative stress in
      apoptosis, we hypothesized that oxidative stress precedes cell death when cocaine
      is administrated. To test this hypothesis, we have monitored the oxidative stress
      and apoptotic effects of acute cocaine exposure in human neuronal progenitor
      cells (HNPC). We found that oxidative stress was significantly increased at 48h
      after a 30min cocaine exposure compared to control cells, and that this was
      followed by cell death at 72h. Using the same experimental paradigm we have
      previously shown that pro-inflammatory genes are up-regulated in cocaine-exposed
      HNPC at 24h. Therefore, we suggest that the increased oxidative stress (possibly
      mediated by inflammatory responses) precedes cell death in cocaine-exposed HNPC.
      This may have implications for the consequences of cocaine abuse in situations
      where antioxidant capacity is compromised, as in the aging brain.

PMID- 16956699
TI  - Induction of antigen-specific cytotoxic T lymphocytes by immunization with
      negatively charged soluble antigen through scavenger receptor-mediated delivery.
AB  - Antigen-specific cytotoxic T lymphocytes (CTL) are essential for the
      immunotherapy against cancer or infection diseases although, conventionally,
      immunization with antigens in soluble form cannot induce CTL. In the present
      study, we have demonstrated for the first time that ovalbumin (OVA)-specific CTL
      can be induced without any adjuvants by immunization with soluble OVA with
      negative charges through scavenger-mediated delivery of antigens to antigen
      presenting cells (APC). Succinylated, maleylated and aconitylated derivatives
      were synthesized to allow the introduction of negative charges. All these
      derivatives can induce OVA-specific CTL and, especially, the CTL activity of mice
      immunized with maleylated derivatives was comparable with that with OVA
      emulsified with CFA, known to be the strongest adjuvant. Efficient antigen
      specific T cell proliferation and IFN-gamma production were also observed for the
      OVA derivatives. The OVA derivatives also showed significant protective effects
      on the growth of OVA-expressing E.G7 tumor cells. In conclusion, the present
      study demonstrates that the introduction of negative charges to soluble antigens
      will be a useful strategy for the development of vaccines.

PMID- 16956700
TI  - The epidemiology and burden of rotavirus in China: a review of the literature
      from 1983 to 2005.
AB  - We reviewed studies of rotavirus in MEDLINE and the Chinese literature to get a
      preliminary estimate of the burden of rotavirus gastroenteritis in China and the
      epidemiology of the disease. Studies were selected if they were conducted for a
      period 1 year or more, had more than 100 patients enrolled, and used an accepted
      diagnostic test. Overall, in 27 reports of children hospitalized for diarrhea in
      urban areas and 3 in rural areas, 44 and 33%, respectively, had rotavirus
      identified as the etiologic agent. Rotavirus was less commonly detected in
      children with milder illness seen in clinics (26% in urban and 28% in rural
      areas) and those cared for in the community (9%). The four main strains of
      rotavirus in circulation worldwide were also found in China and while G1 was the
      predominant strain overall, G3 emerged to be the most common strain in 9 of the
      12 most recent studies. The disease has a distinct winter seasonal pattern and
      affects most children in their first 2 years of life. Although further studies
      are required to fully assess the burden of rotavirus diarrhea before decisions
      can be made about vaccine use, this review suggests that development and
      implementation of rotavirus vaccines should be a national priority.

PMID- 16956701
TI  - Rupture of the flexor digitorum superficialis tendon of the little finger.

PMID- 16956702
TI  - Outer annulus tears have less effect than endplate fracture on stress
      distributions inside intervertebral discs: relevance to disc degeneration.
AB  - BACKGROUND: Annulus tears and endplate fracture are common lesions in human
      intervertebral discs. Both cause degenerative changes in animal models, but the
      time course appears to be different. The purpose of the present experiment is to
      compare the effects of outer annulus tears and endplate fracture on intradiscal
      stresses. We hypothesise that endplate fracture provides a greater stimulus for
      disc degeneration. METHODS: Seven cadaveric lumbar "motion segments" aged 49-70
      years were compressed at 2 kN while the distribution of compressive stress was
      measured in each disc by pulling a 1.3 mm-diameter pressure transducer along its
      mid-sagittal diameter. Measurements were repeated after rim tears were simulated
      by 10 mm-deep scalpel cuts into the outer anterior annulus. The first cut was
      horizontal, 15 mm to the right of the disc midline, near the junction with the
      upper endplate. The second cut was vertical, 15 mm to the left of the disc
      midline, at mid-disc height. The third cut was horizontal, in the disc midline
      and at mid-disc height, so that the cut passed through the needle hole of the
      pressure transducer. Stress profiles were recorded in three postures and at two
      load levels, after each cut. Stress measurements were repeated a final time
      following compressive overload sufficient to fracture the endplate. FINDINGS:
      Outer annulus tears had negligible effect on compressive stress distributions in
      the annulus fibrosus more than 15 mm from the scalpel cut, and they caused
      nucleus pressure to fall by only 1% (SD 1.3%, NS). In contrast, endplate fracture
      reduced nucleus pressure by 37% (P=0.004) and increased maximum stress within the
      posterior annulus by 93% (P=0.033). INTERPRETATION: Outer annulus tears have less
      (immediate) effects on intradiscal compressive stresses than endplate fracture,
      supporting our hypothesis.

PMID- 16956703
TI  - Role of knee kinematics and kinetics on performance and disability in people with
      medial compartment knee osteoarthritis.
AB  - BACKGROUND: Although gait characteristics have been well documented in people
      with knee osteoarthritis, little is known about the relationships between gait
      characteristics and performance or disability. Our purpose was to examine the
      role of knee kinematics and kinetics on walking performance and disability in
      people with knee osteoarthritis. We also examined whether pain mediated the
      relationship between the knee adduction moment and performance or disability.
      METHODS: Three-dimensional gait analysis was conducted on 54 people with medial
      compartment knee osteoarthritis. Performance was quantified with the Six Minute
      Walk test and disability was self-reported on the Short Form-36. The pain
      subscale of the Western Ontario McMaster Universities Osteoarthritis Index and
      the functional self-efficacy subscale of the Arthritis Self-Efficacy scale were
      completed. FINDINGS: A step-wise linear regression demonstrated that the variance
      in Six Minute Walk test scores was explained by functional self-efficacy (50%)
      and the range of knee motion (8%). The variance in Short Form-36 was explained by
      pain (36%), the peak extension angle (19%) and the range of knee motion (4%).
      Pain was unrelated to the knee adduction moment so analyses of pain as a mediator
      of the adduction moment on either performance or disability were halted.
      INTERPRETATION: Kinematic output from the motor control system is useful in
      understanding some variance in current performance and disability in people with
      knee osteoarthritis. The knee adduction moment was unrelated to these variables
      and pain did not mediate between the knee adduction moment and performance or
      disability. Therefore this moment does not explain current clinical status in
      people with knee osteoarthritis based on the measures of performance and
      disability used in this study.

PMID- 16956704
TI  - Asthma disparities in the prevalence, morbidity, and treatment of Latino
      children.
AB  - The paper reviews the existing research related to asthma disparities and frames
      the results of this research within a conceptual model modified from the
      Institute of Medicine model in order to explain asthma health disparities in
      Latino children in the USA. The model of pediatric asthma disparity presented is
      based on the conceptualization of health disparities as the result of a complex
      interaction of factors related to four main domains: the individual and family,
      the environment or context in which the child lives, the health-care system, and
      provider characteristics. Asthma disparities are discussed as they are reflected
      in the process of care (access and quality of treatment) and outcome (prevalence,
      morbidity, severity) experienced by Latino children. The potential mechanisms
      that may account for the asthma disparities documented as reflected by the
      conceptual model proposed are discussed. Finally, several suggestions for future
      research examining determinants that account for asthma disparities are examined.

PMID- 16956705
TI  - Genetic screening as a technique of government: the case of neonatal screening
      for cystic fibrosis in France.
AB  - The biomedicalization process and the rise of genetics that have occurred in the
      last few decades raise political issues concerning the ability of subjects in
      biomedicine to act and make choices. My work examines these issues through a
      study of the process by which neonatal screening for the genetic disease of
      cystic fibrosis (CF) was set up in France. It draws on qualitative interviews
      with 25 national officials making use of the Foucauldian notion of government,
      which implies power relations among entities recognized as subjects of action. I
      examine how different agents (or groups) came to form either governing or
      governable entities within this health policy, and by what means governance in
      this area is exercised. The study positions relations between governors and the
      governed in the dynamics specific to them, showing that screening for CF is, to a
      large degree, a political technique for governing self and others based on a
      biomedical technique. Two types of subject (a professionals' association and a
      patients' association) are seen to be constituted in different ways and endowed
      with more or less extensive power. More generally, the study raises the question
      of the form of the political, through the example of genetic screening.

PMID- 16956706
TI  - Single high dose dexamethasone treatment decreases the pathological score and
      increases the survival rate of paraquat-intoxicated rats.
AB  - Dexamethasone (DEX), a synthetic corticosteroid, has been successfully used in
      clinical practice during paraquat (PQ) poisonings due to its anti-inflammatory
      activity, although, as recently observed, its effects related to de novo
      synthesis of P-glycoprotein (P-gp), may also strongly contribute for its healing
      effects. The main purpose of this study was to evaluate the effects of a single
      high dose DEX administration, which induces de novo synthesis of P-gp, in the
      histological and biochemical parameters in lung, liver, kidney and spleen of
      acute PQ-intoxicated rats. Four groups of rats were constituted: (i) control
      group, (ii) DEX group (100 mg/kg i.p.), (iii) PQ group (25mg/kg i.p.) and (iv)
      PQ+DEX group (DEX injected 2h after PQ). The obtained results showed that DEX
      ameliorated the biochemical and histological lung and liver alterations induced
      by PQ in Wistar rats at the end of 24 hours. This was evidenced by a significant
      reduction in lipid peroxidation (LPO) and carbonyl groups content, as well as by
      normalization of the myeloperoxidase (MPO) activities. Moreover, DEX prevented
      the increase of relative lung weight. On the other hand, these improvements were
      not observed in kidney and spleen of DEX treated rats. Conversely, an increase of
      LPO and carbonyl groups content and aggravation of histological damages were
      observed in the latter tissues. In addition, MPO activity increased in the spleen
      of PQ+DEX group and urinary N-acetyl-beta-D-glucosaminidase activity, a biomarker
      of renal tubular proximal damage, also augmented in this group. Nevertheless, it
      is legitimate to hypothesize that the apparent protection of high dosage DEX
      treatment awards to the lungs of the PQ-intoxicated animals outweighs the
      increased damage to their spleens and kidneys, because a higher survival rate was
      observed, indicating that DEX treatment may constitute an important and valuable
      therapeutic drug to be used against PQ-induced toxicity.

PMID- 16956707
TI  - Modulation of paraoxon toxicity by the cannabinoid receptor agonist WIN 55,212-2.
AB  - Cannabinoids can reduce the pre-synaptic release of acetylcholine and other
      neurotransmitters in the mammalian brain through a retrograde signaling pathway.
      Organophosphorus insecticides elicit toxicity by inhibiting acetylcholinesterase
      and thereby increasing synaptic acetylcholine levels. Several studies suggest
      that some organophosphorus toxicants can potentially modify cannabinergic
      signaling by direct binding to cannabinoid receptors and inhibition of enzymes
      responsible for cannabinoid degradation (i.e., fatty acid amide hydrolase and
      monoacylglycerol lipase). We hypothesized that exposure to the cannabinoid
      receptor agonist WIN 55,212-2 (WIN) could alter the acute toxicity of the
      prototype anticholinesterase, paraoxon. In vitro, paraoxon inhibited hippocampal
      cholinesterase and fatty acid amide hydrolase activities, and displaced specific
      binding to the cannabinoid receptor ligand ([(3)H]CP 55,940) in a concentration
      dependent manner. WIN (0.5, 1.5 or 5mg/kg/day) had a complex dose-related effect
      on locomotor activity when evaluated for 2h after either the first or last of
      seven daily exposures, and significantly decreased hippocampal CB1 binding
      following repeated dosing. Four hours after dosing, paraoxon (0.4 mg/kg, sc)
      elicited classical signs of cholinergic toxicity and significantly reduced
      hippocampal cholinesterase and fatty acid amide hydrolase activities as well as
      [(3)H]CP 55,940 binding. A single exposure to WIN (1.5 mg/kg) significantly
      reduced involuntary movements and SLUD signs following acute paraoxon exposure
      (0.4 and 0.6 mg/kg, sc). In contrast, when rats were challenged with paraoxon
      (0.4 mg/kg) after the seventh daily exposure to WIN (1.5mg/kg/day), involuntary
      movements were significantly increased at later timepoints, while SLUD signs were
      unaffected. These results suggest that acute and repeated exposure to cannabinoid
      agonists may differentially modify acute cholinergic toxicity, possibly through
      modulation of acetylcholine release and adaptation in cannabinergic signaling
      associated with repeated cannabinoid exposures.

PMID- 16956708
TI  - Comparison of styrene and its metabolites styrene oxide and 4-vinylphenol on
      cytotoxicity and glutathione depletion in Clara cells of mice and rats.
AB  - Styrene is a widely used compound in the manufacturing industry. In mice and
      rats, it is both hepatotoxic and pneumotoxic. It causes lung tumors in mice, but
      not in rats. The Clara cell is the main target for the toxicity of styrene and
      its metabolites, and it also has the greatest activity for styrene metabolism.
      Therefore, Clara cells isolated from CD-1 mice and Sprague-Dawley rats were used
      to compare the cytotoxicities induced by styrene and its metabolites. The
      cytotoxicity of styrene was greater in vitro than that of its metabolites styrene
      oxide (racemic, R- and S-) and 4-vinylphenol in contrast with what has been
      observed in vivo in previous studies on hepatotoxicity and pneumotoxicity.
      Susceptibility of rats to styrene and its metabolites are 4-fold less than that
      observed with mice. Glutathione levels were also measured in mice following
      addition of the chemicals in vitro and treatment of the CD-1 mice in vivo.
      Decreases in glutathione concentrations were seen even at doses which did not
      cause the death of mouse Clara cells. Significant decreases in glutathione were
      observed 3h after treatment with racemic SO and R-SO. At 12h, rebound effects
      were seen for all compounds, with all but R-SO rebounding above controls. These
      studies suggest that in vitro cytotoxicity of styrene and its metabolites does
      not strictly follow in vivo effects and that decreases in mouse glutathione
      levels may be related to oxidative stress.

PMID- 16956709
TI  - Nine-year evaluation of a polyacid-modified resin composite/resin composite open
      sandwich technique in Class II cavities.
AB  - OBJECTIVES: The aim of this study was to evaluate in an intraindividual
      comparison the durability of a polyacid-modified resin composite/resin composite
      open sandwich restoration in a 9 years follow-up. A polyacid-modified resin
      composite (PMRC; compomer, Dyract) was placed as an intermediate layer and
      covered with resin composite (RC, Prisma TPH). A direct RC restoration was used
      as control. METHODS: Each of 57 patients, received at least one pair of Class II
      restorations, one open sandwich and one resin composite control. In total 75
      pairs of Class II restorations, 68 premolars and 82 molars, all in occlusion,
      were placed by two dentists. Most of the cavities were surrounded by enamel. The
      restorations were evaluated at baseline, 6, 12, 24, 36 months and 9 years by
      slightly modified USPHS criteria. Survival of restorations grouped on the two
      different techniques was determined using Kaplan-Meier survival curves. RESULTS:
      After 9 years, 14 of 135 evaluated restorations were estimated as unacceptable, 6
      in the sandwich group and 8 in the control group. Over all annual failure rate
      during the 9-year period was 1.1%. The survival rate was not significant
      different between the two techniques (p=0.604). Reasons of failure were:
      secondary caries (8), fracture of tooth (1), fracture of restoration (2),
      endodontic treatment (3). CONCLUSIONS: Both restorative techniques showed good
      durability during the 9-year period. No clinical advantage was observed for the
      sandwich technique.

PMID- 16956710
TI  - Influence of parity on fetal mortality in prolonged pregnancy.
AB  - OBJECTIVE: In England an estimated 50,000 inductions of labour at or beyond 41
      weeks' gestation are conducted each year. However, the published evidence on the
      effect of parity on stillbirth in prolonged pregnancy is limited, and has
      produced conflicting data. The aim of this study is to evaluate the influence of
      parity on fetal mortality in prolonged pregnancies. STUDY DESIGN: Retrospective
      analysis of 145,695 singleton births with known parity and no malformation noted
      at birth to residents in the former North-East Thames Region, UK. The parity and
      gestation specific stillbirth risks and relative risks per 1000 ongoing
      pregnancies were calculated in relation to parity between 37 and 45 weeks.
      RESULTS: Before 41 weeks the stillbirth risk rose gradually but did not differ by
      parity. By 41 weeks there was a substantial increase in the stillbirth risk in
      nulliparous women but not in parous women. The pattern of rise is such that the
      stillbirth risk is 2.9 times higher (95% CI 1.06-8.19) in nulliparous women at
      >42 weeks' gestation. CONCLUSION: Being parous appears to have a protective
      effect on fetal mortality in prolonged pregnancy. These findings question the
      need for routine induction of labour at 41 weeks in parous women.

PMID- 16956711
TI  - Simultaneous radioassays of bacterial production and mercury methylation in the
      periphyton of a tropical and a temperate wetland.
AB  - Laboratory radioassays were made to study mercury (Hg) methylation together with
      bacterial production in the periphyton of two aquatic macrophytes, the submerged
      Myriophyllum spicatum, from a constructed wetland in Sweden and the floating
      Eichhornia crassipes, from a eutrophied tropical lake in Brazil. Time course
      incubations were made by addition of (203)HgCl(2) and the methylmercury formed
      was extracted at pre-defined time intervals. Bacterial production ((14)C-leucine
      incorporation) was measured at the same time intervals, with plants removed from
      parallel incubations made with and without addition of cold HgCl(2). For E.
      crassipes, higher methylmercury production was observed at elevated bacterial
      production, whereas for M. spicatum, the bacterial production was significantly
      lower, and Hg methylation was below the detection limit. The combined results
      confirm the importance of microbial processes for Hg methylation, although other
      factors are known to influence this process in complex ways. The addition of Hg
      did not significantly influence bacterial production, while the incubation
      temperatures used (25 and 35 degrees C) resulted in different methylation rates.
      Radiotracer techniques for measurements of bacterial production such as (14)C
      leucine uptake can provide useful insights into the Hg cycle in aquatic
      environments, and our data suggest that they may be used as a proxy of mercury
      methylation potentials.

PMID- 16956712
TI  - Prognostic value of CpG island hypermethylation at PTGS2, RAR-beta, EDNRB, and
      other gene loci in patients undergoing radical prostatectomy.
AB  - OBJECTIVES: To evaluate CpG island hypermethylation in a set of candidate genes
      in prostate cancer (pCA) and its relationship to clinicopathologic parameters and
      a nomogram predicting prostate-specific antigen (PSA) recurrence after radical
      prostatectomy. MATERIALS AND METHODS: Tissues of 78 prostate carcinomas, 32
      benign prostate hyperplasias (BPHs), and prostate cell lines (LNCaP, DU145, PC3,
      BPH-1) were examined with MethyLight polymerase chain reaction at 13 gene loci
      (APC, CDC6, CTNNB1, E-Cadherin, EDNRB, FGFR2, GSTP1, NAB2, PKCmu, PTGS2, RAR
      beta, RASL11A, WWOX). RESULTS: APC, RAR-beta, PTGS2, GSTP1, EDNRB, and CTNNB1
      (83%, 71%, 65%, 33%, 14%, 9%, respectively) were methylated in pCA but rarely or
      not methylated in BPH. NAB2 and CDC6 were hypermethylated frequently in pCA (92%,
      67%, respectively) and in BPH (91%, 59%, respectively). FGFR2, WWOX, E-Cadherin,
      PKCmu, and RASLL1A did not display noteworthy methylation in pCA (0-1%) or in
      BPH. CpG island hypermethylation at APC, retinoic acid receptor beta (RAR-beta),
      and PTGS2 discriminated with a sensitivity of 65-83% and a specificity of 97-100%
      between BPH and pCA. The combination of various genes increased the diagnostic
      expressiveness. PTGS2 hypermethylation correlated with seminal vesicle
      infiltration (p=0.047), capsular penetration (p=0.004), and pT stage (p=0.014).
      RAR-beta methylation was accompanied by a higher cumulative Gleason score
      (p=0.042). The probability of PSA-free-survival calculated with a Kattan nomogram
      correlated inversely with CpG island hypermethylation at EDNRB, RAR-beta, and
      PTGS2. All prostate cancer cell lines displayed a varying degree of demethylation
      after 5-aza-2'deoxycytidine treatment. CONCLUSIONS: CpG island hypermethylation
      at various gene loci is frequent in prostate cancer and can distinguish between
      neoplastic and noncancerous tissue. Furthermore, hypermethylation at PTGS2, RAR
      beta, and EDNRB inversely correlated with PSA-free-survival according to a Kattan
      nomogram and has potential prognostic value.

PMID- 16956713
TI  - Acute urodynamic effects of posterior tibial nerve stimulation on neurogenic
      detrusor overactivity in patients with MS.
AB  - OBJECTIVES: The aim of this study was to investigate whether acute electrical
      stimulation of the posterior tibial nerve could suppress detrusor contractions in
      multiple sclerosis (MS) patients with neurogenic detrusor overactivity. METHODS:
      Two successive slow-fill cystometries (16 ml/min) were carried out in eight MS
      patients with neurogenic detrusor overactivity. The first filling served as
      control without stimulation. In the second filling, electrical stimulation using
      needle electrodes was applied automatically to the posterior tibial nerve when
      the detrusor pressure exceeded 10 cm H(2)O. An additional filling in which the
      needle electrodes were replaced by surface electrodes was carried out in three
      patients. RESULTS: The control filling showed detrusor overactivity in eight
      patients, but electrical stimulation of the posterior tibial nerve failed to
      suppress detrusor contractions in all tested patients. CONCLUSIONS: Although
      neuromodulative effects may be obtained with therapeutic electrical stimulation
      of the posterior tibial nerve, no acute effects were demonstrated. For this
      reason, electrical stimulation of pudendal afferents remains the only option if
      acute suppression of a detrusor contraction is required.

PMID- 16956714
TI  - Morbidity from pelvic lymphadenectomy in men undergoing radical prostatectomy.

PMID- 16956715
TI  - Minimising postoperative incontinence following radical prostatectomy:
      considerations and evidence.
AB  - OBJECTIVES: To review evidence regarding perioperative predictors of incontinence
      after radical prostatectomy (RP), related anatomic and patient factors, and
      surgical techniques used to minimise incontinence. METHODS: A search of the
      Pubmed, Cancerlit, Cochrane, and ISI Web of Science databases was performed for
      the key words prostatectomy, incontinence, and continence. Relevant articles were
      reviewed, summarised, and analysed. RESULTS: Enhanced understanding of pelvic
      anatomy applied to surgical approaches has improved continence rates following
      RP; however, incontinence remains a potential adverse outcome. Evidence suggests
      that increasing patient body weight and prostate volume are not associated with
      continence outcomes, but increasing patient age may be predictive. Behavioural
      therapy may aid in early return to continence although the timing of therapy and
      benefit of biofeedback assistance are unclear. Various surgical techniques are
      used to improve continence, but no evidence overwhelmingly supports any specific
      technique. At best, evidence supports early return to continence with some
      techniques. No technique significantly increased margin positivity solely at the
      experimental anatomic site. CONCLUSIONS: Despite enhanced knowledge of anatomy
      and improved surgical approach, incontinence persists as a potential adverse
      outcome of RP. Urologists may not find an evidence-based rationalisation for any
      particular surgical technique due to the nature of surgical series, variability
      in the definition of incontinence, and individual surgical skills, preferences,
      and techniques. Giving careful consideration to the trial design can potentially
      improve the resulting level of evidence.

PMID- 16956716
TI  - Removal of iron from groundwater by ash: a systematic study of a traditional
      method.
AB  - A traditional method for removal of iron from ground water by using ash has been
      systematically investigated. Ashes from five different sources, viz., banana
      rind, banana pseudostem, banana leaf, rice husk and bamboo has been studied. The
      principle applied is enhanced precipitation of iron at high pH caused by ash. The
      study included laboratory analysis of some relevant chemical parameters of the
      ashes and the efficiency of the ashes in removing iron from prefabricated water
      with respect to quantity of ash and corresponding increase in pH of water. The
      ash of banana pseudostem has been found to be most suitable for removal of iron.
      A low-cost and easily made iron removal system for household use has been
      designed and tested in the laboratory. The ash of banana pseudostem has been
      found to remove iron to below 0.3ppm without increasing the pH above the
      acceptable limit. The optimum values of the different parameters for removal of
      iron are 200-300mgl(-1) ash, 1.0lh(-1) flow rate and 1h of contact time with ash
      for groundwater having [Fe] of about 2.20ppm. The amount of ash can be increased
      for groundwater having higher [Fe] and can be decreased gradually during
      continuous use of the system. Acceptability of the method has been examined based
      on chemical analysis of the treated water. Increase in the essential minerals
      such as Ca, K has been observed in the water after treatment. The designed iron
      removing system is expected to be suitable for household use.

PMID- 16956717
TI  - Detoxification of olive mill wastewater by electrocoagulation and sedimentation
      processes.
AB  - Olive mill wastewater (OMW) is characterised by its high suspended solids content
      (SS), high turbidity (NTU), chemical oxygen demand (COD) concentration up to 100
      gl(-1) and toxic phenolic compounds concentration up to 10 gl(-1). This study
      examined the effect of a physico-electrochemical method to detoxify olive mill
      wastewater prior an anaerobic biotreatment process. The proposed pre-treatment
      process consisted in a preliminary electrocoagulation step in which most phenolic
      compounds were polymerised, followed by a sedimentation step. The BOD(5)/COD
      ratio of the electrocoagulated OMW increased from 0.33, initial value, to 0.58.
      Furthermore, the sedimentation step yielded the removal of 76.2%, 75% and 71% of
      phenolic compounds, turbidity and suspended solid, respectively, after 3 days of
      plain settling. The combination of electrocoagulation and sedimentation allowed a
      COD reduction and decoloration of about 43% and 90%, respectively. This pre
      treatment decreases the inhibition of Vibrio fisheri luminescence by 66.4%.
      Continuous anaerobic biomethanization experiments conducted in parallel with raw
      OMW and electrocoagulated OMW before and after sedimentation at a loading rate of
      6g COD l(-1)day(-1), proved that the final pre-treated OMW was bioconverted into
      methane at high yield while raw OMW was very toxic to anaerobic microorganisms.

PMID- 16956718
TI  - Adsorption characteristics of As(III) from aqueous solution on iron oxide coated
      cement (IOCC).
AB  - Contamination of potable groundwater with arsenic is a serious health hazard,
      which calls for proper treatment before its use as drinking water. The objective
      of the present study is to assess the effectiveness of iron oxide coated cement
      (IOCC) for As(III) adsorption from aqueous solution. Batch studies were conducted
      to study As(III) adsorption onto IOCC at ambient temperature as a function of
      adsorbent dose, pH, contact time, initial arsenic concentration and temperature.
      Kinetics reveal that the uptake of As(III) ion is very rapid and most of fixation
      occurs within the first 20 min of contact. The pseudo-second order rate equation
      successfully described the adsorption kinetics. Langmuir, Freundlich, Redlich
      Peterson (R-P), and Dubinin-Radushkevich (D-R) models were used to describe the
      adsorption isotherms at different initial As(III) concentrations and at 30 g l(
      1) fixed adsorbent dose. The maximum adsorption capacity of IOCC for As(III)
      determined from the Langmuir isotherm was 0.69 mg g(-1). The mean free energy of
      adsorption (E) calculated from the D-R isotherm was found to be 2.86 kJ mol(-1)
      which suggests physisorption. Thermodynamic parameters indicate an exothermic
      nature of adsorption and a spontaneous and favourable process. The results
      suggest that IOCC can be suitably used for As(III) removal from aqueous
      solutions.

PMID- 16956719
TI  - Determining heats of detonation of non-aromatic energetic compounds without
      considering their heats of formation.
AB  - A new procedure is introduced for calculating heats of detonation of non-aromatic
      energetic compounds through ratios of oxygen to carbon and hydrogen to oxygen as
      well as the contribution of some structural parameters. There is no need to use
      heats of formation of non-aromatic energetic compounds that are usually needed by
      the other methods. Moreover, this much simple method does not use any
      experimental and computed data of energetic materials. Predicted heats of
      detonation for 28 non-aromatic energetic compounds have a root mean square (rms)
      of deviation of 0.54 kJ/g from experiment, which show good agreement with respect
      to measured values. The new method is the simplest procedure for predicting heats
      of detonation and provides reliable results which are comparable with the other
      methods.

PMID- 16956720
TI  - Adsorption of methylene blue onto bamboo-based activated carbon: kinetics and
      equilibrium studies.
AB  - Bamboo, an abundant and inexpensive natural resource in Malaysia was used to
      prepare activated carbon by physiochemical activation with potassium hydroxide
      (KOH) and carbon dioxide (CO(2)) as the activating agents at 850 degrees C for
      2h. The adsorption equilibrium and kinetics of methylene blue dye on such carbon
      were then examined at 30 degrees C. Adsorption isotherm of the methylene blue
      (MB) on the activated carbon was determined and correlated with common isotherm
      equations. The equilibrium data for methylene blue adsorption well fitted to the
      Langmuir equation, with maximum monolayer adsorption capacity of 454.2mg/g. Two
      simplified kinetic models including pseudo-first-order and pseudo-second-order
      equation were selected to follow the adsorption processes. The adsorption of
      methylene blue could be best described by the pseudo-second-order equation. The
      kinetic parameters of this best-fit model were calculated and discussed.

PMID- 16956721
TI  - Flashing liquid jets and two-phase droplet dispersion I. Experiments for
      derivation of droplet atomisation correlations.
AB  - The large-scale release of a liquid contained at upstream conditions above its
      local atmospheric boiling point is a scenario often given consideration in
      process industry risk analysis. Current-hazard quantification software often
      employs simplistic equilibrium two-phase approaches. Scaled water experiments
      have been carried out measuring droplet velocity and droplet size distributions
      for a range of exit orifice aspect ratios (L/d) and conditions representing low
      to high superheat. 2D Phase-Doppler Anemometry has been utilised to characterise
      droplet kinematics and spray quality. Droplet size correlations have been
      developed for non-flashing, the transition between non-flashing and flashing, and
      fully flashing jets. Using high-speed shadowography, transition between regimes
      is defined in terms of criteria identified in the external flow structure. An
      overview companion paper provides a wider overview of the problem and reports
      implementation of these correlations into consequence models and subsequent
      validation. The fluid utilised throughout is water, hence droplet correlations
      are developed in non-dimensional form to allow extrapolation to other fluids
      through similarity scaling, although verification of model performance for other
      fluids is required in future studies. Data is reduced via non-dimensionalisation
      in terms of the Weber number and Jakob number, essentially representing the fluid
      mechanics and thermodynamics of the system, respectively. A droplet-size
      distribution correlation has also been developed, conveniently presented as a
      volume undersize distribution based on the Rosin-Rammler distribution. Separate
      correlations are provided for sub-cooled mechanical break-up and fully flashing
      jets. This form of correlation facilitates rapid estimates of likely mass rainout
      quantities, as well as full distribution information for more rigorous two-phase
      thermodynamic modelling in the future.

PMID- 16956722
TI  - Biosorption of Cr(VI) by native isolate of Lyngbya putealis (HH-15) in the
      presence of salts.
AB  - Industrial wastewaters containing heavy metals along with high concentration of
      soluble salts pose a major environmental problem that needs to be remedied. The
      present study reports on biosorption of Cr(VI) by native isolate of Lyngbya
      putealis HH-15 in batch system under varying range of pH (2.0-10.0), initial
      metal ion concentration (10-100mg/l) and salt concentration (0-0.2%). Maximum
      metal removal (94.8%) took place at pH 3.0 with initial Cr concentration of
      50mg/l, which got reduced (90.1%) in the presence of 0.2% salts. Adsorption
      equilibrium and kinetic behavior of Cr(VI) in solution was also examined. Both
      Langmuir and Freundlich models fitted well to explain the adsorption data
      (R(2)=0.90 and 0.87, respectively) at 0.2% salt concentration. Pseudo-second
      order kinetic model also fitted well to both the systems, viz. Cr(VI) and
      Cr(VI)+salt.

PMID- 16956723
TI  - Automatic on-line pre-concentration system using a knotted reactor for the FAAS
      determination of lead in drinking water.
AB  - An automatic on-line pre-concentration system is proposed for lead determination
      in drinking water using flame atomic absorption spectrometry (FAAS). Lead(II)
      ions are retained as the 1-(2-pyridylazo)-2-naphthol (PAN) complex in the walls
      of a knotted reactor, followed by an elution step using 0.50molL(-1) hydrochloric
      acid solution. Optimisation involving the sampling flow rate, pH and buffer
      concentration factors was performed using a Box-Behnken design. Other factors
      were established considering results of previous experiments. The procedure
      allows the determination of lead with a 0.43microgL(-1) detection limit
      (3sigma/S) and precisions (expressed as relative standard deviation) of 4.84%
      (N=7) and 2.9% (N=7) for lead concentrations of 5 and 25microgL(-1),
      respectively. The accuracy was confirmed by the determination of lead in the NIST
      SRM 1643d trace elements in natural water standard reference material. The pre
      concentration factor obtained is 26.5 and the sampling frequency is 48h(-1). The
      recovery achieved for lead determination in the presence of several ions
      demonstrated that this procedure could be applied to the analysis of drinking
      water samples. The method was applied for lead determination in drinking water
      samples collected in Jequie City, Brazil. The lead concentration found in 25
      samples were always lower than the permissible maximum levels stipulated by World
      Health Organization.

PMID- 16956724
TI  - Effects of sodium hypochlorite and high pH buffer solution in electrokinetic soil
      treatment on soil chromium removal and the functional diversity of soil microbial
      community.
AB  - Effects of sodium hypochlorite (NaClO), applied as an oxidant in catholyte, and
      high pH buffer solution on soil Cr removal and the functional diversity of soil
      microbial community during enhanced electrokinetic treatments of a chromium (Cr)
      contaminated red soil are evaluated. Using pH control system to maintain high
      alkalinity of soil together with the use of NaClO increased the electrical
      conductivities of soil pore liquid and electroosmotic flux compared with the
      control (Exp-01). The pH control and NaClO improved the removal of Cr(VI) and
      total Cr from the soil. The highest removal percentages of soil Cr(VI) and total
      Cr were 96 and 72%, respectively, in Exp-04 when the pH value of the anolyte was
      controlled at 10 and NaClO was added in the catholyte. The alkaline soil
      environment and introduction of NaClO in the soil enhanced the desorption of
      Cr(VI) from the soil and promoted Cr(III) oxidation to mobile Cr(VI),
      respectively. However, the elevated pH and introduction of NaClO in the soil,
      which are necessary for improving the removal efficiency of soil Cr, resulted in
      a significantly adverse impact on the functional diversity of soil microbial
      community. It suggests that to assess the negative impact of extreme conditions
      for enhancing the extraction efficiencies of Cr on the soil properties and
      function is necessary.

PMID- 16956725
TI  - Novel correlation for predicting impact sensitivity of nitroheterocyclic
      energetic molecules.
AB  - A novel correlation is introduced for predicting impact sensitivity of a variety
      nitroheterocyclic molecular types, such as nitropyridines, nitroimidazoles,
      nitropyrazoles, nitrofurazanes, nitrotriazoles and nitropyrimidines. This
      approach is based on elemental composition and two structural parameters of
      C(a)H(b)N(c)O(d) nitroheterocyclic energetic compounds. The results for mentioned
      compounds are compared with complex neural networks computations which use
      compositional and topological descriptors. Root mean square (rms) of deviation of
      different nitroheterocyclic molecules including nitropyridines, nitroimidazoles,
      nitropyrazoles, nitrofurazanes, nitrotriazoles and nitropyrimidines are 58 and
      71cm for new correlation and neural networks computations methods, respectively.

PMID- 16956726
TI  - Response to editorial on Sharav and Tal (2006).

PMID- 16956727
TI  - Risk factors associated with porcine cysticercosis in selected districts of
      Eastern and Southern provinces of Zambia.
AB  - To determine the risk factors associated with Taenia solium transmission in
      humans and pigs in the rural areas of Eastern and Southern provinces of Zambia, a
      questionnaire was administered in 788 households from 155 villages. Pigs were
      examined from 800 households. Tongue examination and enzyme-linked immunosorbent
      assay (Ag-ELISA) for the detection of circulating antigens of T. solium
      cysticerci were used to measure infection in pigs. A snowballing technique was
      utilised to select households with pigs. Prevalence of households with pigs
      infected with T. solium on tongue examination by district ranged from 12.7% to
      32.1% with Ag-ELISA having a range of 30.0-51.7%. Of the total number of
      households visited, 18.8% and 37.6% had at least one pig positive for porcine
      cysticercosis on tongue examination and Ag-ELISA, respectively. Risk factors
      associated with T. solium infection were lack of pork inspection at slaughter
      (96.7%), consumption of pork with cysts (20.1%), selling of pork infected with T.
      solium cysticerci (18.3%), free-range husbandry system (83.2%) and absence of
      latrines (58.0). Free-range husbandry system (OR=1.68; 95% CI=1.36-2.07) was a
      significant risk factor for porcine cysticercosis in the surveyed areas. The
      result that pigs were mostly kept on free-range and semi-intensive husbandry
      systems may have permitted them to have access to eating human faeces that could
      be contaminated with tapeworm eggs. This study has shown that T. solium infection
      poses a high public health risk in the study areas and urban areas as well. We
      recommend that a human survey be conducted to verify the human exposure to
      taeniasis and/or cysticercosis in Zambia.

PMID- 16956728
TI  - Serological survey of Neospora caninum in dogs in the Czech Republic and a long
      term study of dynamics of antibodies.
AB  - The main aim of the present study was to establish the prevalence of antibodies
      against Neospora caninum dogs from the Czech Republic and to examine the dynamics
      of antibody titers during a long-term period. For this purpose, sera of 858 dogs
      were examined for the presence of anti-N. caninum antibodies using an indirect
      immunofluorescent antibody test (IFAT). Four groups of dogs of various origins
      were included in the survey: the first group (A, n=470) comprised dogs purchased
      by the Czech Army from the civilian sector throughout the Czech Republic, with 22
      (4.7%) N. caninum-positive dogs, second group (B, n=115) represented police dogs
      with no seropositive animal, third group (C, n=195) were pet dog sera collected
      for veterinary clinic with 5 (2.6%) anti-N. caninum sera and the fourth group (D,
      n=78) of canine shelter dogs with the seroprevalence of 19.2%. The differences in
      seroprevalence were significant (P< or =0.01) between groups B and A, and between
      D and A. None of the serologically positive animals had clinical signs of
      neurological disorders. Coprological examination did not reveal any dog shedding
      N. caninum oocysts. The seropositivity rates for N. caninum were analyzed in
      relation to other data, such as age, breed and gender. Increased prevalence rates
      of anti-N. caninum antibodies were found in the older age strata of the dog
      population sample tested in the present study. We found significantly higher
      (P=0.02) prevalence in 3-3.5-year-old dogs (11.1% of 36), as compared to 1-1.5
      years-old dogs (2% of 98). A longitudinal study of antibody dynamics was carried
      out in 19 initially seropositive dogs over a period of 4 years. The second and
      third examinations revealed that antibody titers decreased in majority of
      positive dogs (10, 52.6%), of which in seven cases (36.8%) the titers fell to
      levels that are currently considered as being seronegative (titer <1:50), or even
      became undetectable (titer <1:25).

PMID- 16956729
TI  - High-resolution predictive mapping for Boophilus annulatus and B. microplus
      (Acari: Ixodidae) in Mexico and Southern Texas.
AB  - In this study we use high-resolution satellite imagery to map habitat suitability
      for both Boophilus annulatus and B. microplus over an area covering parts of
      Texas and northeastern Mexico. The habitat for these tick species covers widely
      different regions. B. microplus finds satisfactory abiotic conditions in wet
      coastal habitats, whereas B. annulatus finds suitable habitat in the drier inner
      parts of southwestern Texas and northern Mexico; the two species have very
      different habitat requirements. We use habitat topology and data concerning
      abiotic habitat suitability to understand the effects of habitat configuration on
      tick abundance. This is achieved using traversability (habitat permeability) and
      recruitment (tick abundance at the patch level) to produce a model that computes
      the abundance of ticks at the patch level. Results from the computation are then
      compared with actual data on tick outbreaks at the Texas-Mexico border, as a test
      of the agreement between actual tick captures and abundance model predictions.

PMID- 16956730
TI  - Treatment of solid tumors and metastases by fibrinogen-targeted anticancer drug
      therapy.
AB  - The accumulation of fibrin/fibrinogen and other coagulation factors in and around
      solid tumors and metastatic foci has been recognized for a century as an aspect
      of cancer pathology. On this basis, anticoagulants and fibrinolytic agents have
      been deployed as adjuvant anticancer therapies, but they have proved clinically
      useful for only a small proportion of tumors and they only control the functions
      of the coagulant components. Overuse or long-term application of anticoagulants
      and fibrinolytic agents often lead to undesirable side-effects. Here, we propose
      that anticancer drugs that act by different mechanisms can inhibit tumor
      associated coagulation, and it may be possible to develop drugs that specifically
      targeting tumor-related coagulation, have specific cytotoxic effects on tumor and
      metastatic cells. We provide laboratory and clinical evidence supporting the
      hypothesis and offer proposals for future applications.

PMID- 16956731
TI  - Silymarin and its components scavenge phenylglyoxylic ketyl radicals.
AB  - The antioxidant properties of silymarin and its flavanolignan components
      (silybin, silychristin and silydianin) were tested. Silymarin, silychristin and
      silydianin exhibit relatively good antioxidant effectiveness against
      phenylglyoxylic ketyl radicals and DPPH. The most effective scavengers of
      phenylglyoxylic ketyl radicals were silymarin and silychristin whereas silydianin
      was ca. 5-times less active than the first two compounds whereas silybin was
      ineffective. The scavenging properties of the studied compounds against DPPH
      radicals were in the same sequence: silymarin>silychristin>silydianin>silybin.

PMID- 16956732
TI  - In what sense are addicts irrational?
AB  - Rationality is here considered from a functional viewpoint: How may the concept
      of rationality be best used in talking about addictive behavior? The article
      considers rationality in terms of overt behavioral patterns rather than as a
      smoothly operating logic mechanism in the head. The economic notion of
      rationality as consistency in choice - the property of exponential time discount
      functions - is examined and rejected. Addicts are not irrational because of the
      type of time discount function that governs their choices-or even because of the
      steepness of that function. Instead, rationality is here conceived as a pattern
      of predicting your own future behavior and acting upon those predictions to
      maximize reinforcement in the long run. Addicts are irrational to the extent that
      they fail to make such predictions and to take such actions.

PMID- 16956733
TI  - The role of conduct disorder in explaining the comorbidity between alcohol and
      illicit drug dependence in adolescence.
AB  - BACKGROUND: Conduct disorder (CD), alcohol dependence (AD), and illicit drug
      dependence (IDD) frequently co-occur. This paper describes the result of an
      investigation of the extent to which comorbid alcohol and illicit drug dependence
      in adolescents are explained by etiological factors in common with conduct
      disorder. METHODS: Participants were 645 MZ twin pairs, 702 DZ twin pairs, 429
      biological sibling pairs, and 96 adoptive sibling pairs, aged 12-18 years, from a
      community based sample. Conduct disorder was measured using the Diagnostic
      Interview Schedule for Children-IV. Alcohol and illicit drug dependence were
      assessed using the Composite International Diagnostic Interview-Substance Abuse
      Module (CIDI-SAM). For each outcome, subjects were categorized into those with no
      symptoms, those with one or more symptoms but no diagnosis, and those with a
      diagnosis. RESULTS: The heritability estimates for CD, AD, and IDD were 58, 66,
      and 36%, respectively. The genetic correlation between AD and IDD was partially
      explained by the genetic risk they both share with conduct disorder. CONCLUSIONS:
      We conclude that conduct disorder in adolescents explains, in part, the co
      occurrence of alcohol and illicit drug dependence. Specifically, the genetic
      contribution to their covariation is explained partially by the genetic
      contribution in common with conduct disorder.

PMID- 16956734
TI  - Intra-specific variability and unusual organization of the repetitive units in a
      satellite DNA from Rana dalmatina: molecular evidence of a new mechanism of DNA
      repair acting on satellite DNA.
AB  - We have characterized the S1 satellite from eight European populations of Rana
      dalmatina by Southern blot, cloning and a new method that determines the sequence
      variability of repetitive units in the genome. This report completes our previous
      studies on this satellite DNA family, thus providing the first characterization
      of the overall variability of the structure and genomic organization of a
      satellite DNA within a species and among related species. The S1 satellite from
      R. dalmatina has a pericentromeric location on ten chromosome pairs and presents
      two homologous repeats S1a (494 bp) and S1b (332 bp), mostly organized as
      composite S1a-S1b repetitive units. In other brown frog species, both repeats
      have different sequences and locations, and are usually organized as separate
      arrays, although composite S1a-S1b repeats represent a minor, widely variable
      component in Rana italica. The average genomic sequences indicate that the
      species contains an enormous number of variants of each repeat derived from a
      unique, species-specific common sequence. The repeat variability is restricted to
      specific base changes in specific sequence positions in all population samples.
      Our data show that the structure and evolution of S1 satellite family is not due
      to crossing-over and gene conversion, but to a mechanism that maintains the
      ability of the satellite DNA to assemble in constitutive heterochromatin by
      replacing altered satellite segments with new arrays generated by rolling circle
      amplification. The mode of action of this repair process not only directly
      explains the intra- and inter-specific variability of the structure and
      organization of the S1 satellite repeats from European brown frogs, but also
      accounts for all general features of satellite DNA in eukaryotes, including its
      discontinuous evolution. This repair mechanism can maintain the satellite
      structure in a species indefinitely, but also promote a rapid generation of new
      variants or types of satellite DNA when environmental conditions favor the
      formation of new species.

PMID- 16956735
TI  - Analysis of national serological surveys for the documentation of freedom from
      porcine reproductive and respiratory syndrome in Switzerland.
AB  - Results of national serological surveys for porcine reproductive and respiratory
      syndrome (PRRS) conducted in Switzerland in 2001 and 2004 were analyzed. In 2001,
      41,124 breeding sows from 2,540 herds out of 6,406 were sampled, and in 2004,
      7,498 animals were sampled from 1,074 herds out of 5,320. All serum samples were
      tested for PRRS using an ELISA developed at the Institute of Virology and
      Immunoprophylaxis (IVI), Switzerland with a sensitivity (Se) and specificity (Sp)
      of 94 and 97%, respectively. Positive samples were re-tested with a commercial
      ELISA (IDEXX) with Se of 100% and Sp of 99%. Samples positive in the second test
      were confirmed with the fluorescent antibody test (FAT). A stochastic model using
      data from the main survey conducted in 2001 was done to verify whether the
      sampling scheme used could detect at least one infected herd with 99% confidence
      level if the herd designed prevalence was at 0.1 or 0.2%. Additionally, a
      Bayesian approach was conducted to calculate the post-survey probability of
      freedom from PRRS using data from the 2001 and 2004 surveys. A Monte Carlo
      simulation with 5000 iteration was run for each model. Eleven samples in 2001 and
      six in 2004, all from different farms, could not be conclusively confirmed as
      negative by the FAT. All other samples were negative. Truly infected animals and
      herds were not predicted by a stochastic model at the 99% confidence level and
      0.1% herd prevalence using data from the 2001 survey. However, it was
      demonstrated that the prior probability of freedom from PRRS increased from 89.3
      to 99.2% after the 2001 survey. Upon completion of the 2004 survey, the
      probability of freedom from PRRS reached a value of 99.7%. Based on our results,
      we could conclude that the pig industry in Switzerland is free of PRRS virus with
      this level of confidence. Restricted import activities over the last decades are
      a possible explanation for the continuing absence of PRRS-infection in the Swiss
      swine population. Import requirements defined by the pig industry minimize the
      risk of introduction of PRRS-infected animals in the future.

PMID- 16956736
TI  - PDGF-C participates in branchial arch morphogenesis and is down-regulated by
      retinoic acid.
AB  - Retinoic acid (RA) is a teratogen that induces a variety of craniofacial
      abnormalities, including branchial arch deformities and cleft palate. Platelet
      derived growth factor C (PDGF-C) is a recently identified member of the PDGF
      family. PDGF-C contributes to normal development of the heart, central nervous
      system, kidney and palatogenesis. But the roles of PDGF-C in branchial arches
      development and the relationship between PDGF-C and RA-induced branchial arches
      abnormalities are poorly understood. We examined the effects of RA on PDGF-C and
      its receptor PDGFR-alpha expressions. We demonstrated that administration of RA
      to mouse embryos resulted in dramatic losses of PDGF-C and its receptor PDGFR
      alpha. Furthermore, we confirmed that blocking PDGF-C signaling by anti-PDGF-C
      neutralization antibody led to branchial arch malformations similar to that of RA
      induced, both hypoplastic branchial arches and FBA. These findings suggest the
      down-regulation of PDGF-C may be one of mechanisms of branchial arch
      abnormalities induced by RA and PDGF-C signaling is required for branchial arch
      morphogenesis.

PMID- 16956737
TI  - Beta-catenin localization and timing of early development of bovine embryos
      obtained from oocytes matured in the presence of follicle stimulating hormone.
AB  - In mammalian species, embryos which grow more rapidly are believed to be more
      competent and viable than they are slower developing counterparts. Although the
      most important decrease in development occurs between the zygote and blastocyst
      stages, there is a growing amount of evidence to suggest that maturation
      conditions and oocyte quality have a profound influence on the developmental
      potential of early mammalian embryos. Gene transcripts and polypeptides stored in
      the oocytes, such as junctional proteins, sustain the initial development of
      embryos. In the present study we demonstrated a relationship between the timing
      of the development of in vitro-produced bovine embryos and the distribution and
      localization of the junctional protein beta-catenin. We further demonstrated that
      the presence of FSH during IVM supports cleavage and the blastocyst rate, and
      also has a positive effect on the speed of development, since embryos obtained
      from oocytes matured with the gonadotropin and observed on days 4, 5 and 6 post
      insemination (p.i.) grew faster than those matured in a medium supplemented with
      BSA. Moreover, the majority of embryos which developed past the 16-cell stage
      showed a proper distribution of beta-catenin just beneath the membrane surfaces
      of all blastomeres and an appropriate morphology, as confirmed by transmission
      electron microscopy (TEM) and scanning electron microscopy (SEM) analysis. In
      conclusion, our data suggest that supplementing FSH during in vitro maturation
      aids the development of bovine embryos and promotes the correct expression of
      beta-catenin, increasing the likelihood that embryos will develop to the
      blastocyst stage.

PMID- 16956738
TI  - Bacterial complications of postpartum uterine involution in cattle.
AB  - The bacterial contamination of the postpartum uterus is a frequent finding which
      by itself does not disturb the anatomical and histological restoration of tubular
      genital tract. The improper balance between uterine infection and the
      intrauterine antimicrobial self-defence mechanisms, however, often results in
      complications, such as puerperal metritis, clinical endometritis, pyometra and
      subclinical endometritis. After reviewing the bacteriology of uterine involution,
      and the predisposing factors for its bacterial complications, this paper defines
      the different clinical forms, and summarizes their pathology, furthermore, the
      recent progress in diagnostic considerations and principles of current treatments
      for these diseases of bovine genitals.

PMID- 16956739
TI  - Haplotype analysis of 17 Y-STR loci in a Japanese population.
AB  - We analyzed 17 Y-STR loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392,
      DYS393, DYS385a/b, DYS438, DYS439, DYS456, DYS458 and DYS464a/b/c/d) in 252
      Japanese males using three multiplex PCR typing systems. Two variants were found
      at DYS385a/b. A total of 244 different haplotypes were observed, of which 239
      were found in single individuals. The haplotype diversity for the 17 loci was
      0.996.

PMID- 16956740
TI  - Evaluation of methods for the determination of water in substances with unknown
      chemical and thermal behaviour.
AB  - The water content of six different substances was determined by means of five
      different methods. The methods used were loss on drying, thermogravimetry
      (coupled with DSC), a new phosphorous-pentoxide method, direct Karl-Fischer
      titration and the Karl-Fischer oven. A combination of direct Karl-Fischer
      titration and the KF-oven method was found to be the optimal technique for water
      determination of substances of unidentified chemical and thermal behaviour based
      on detailed considerations about selectivity, type of water binding, sample
      properties and efficiency.

PMID- 16956741
TI  - A direct HPLC method to estimate streptomycin and its putative ototoxic
      derivative, streptidine, in blood serum: application to streptomycin-treated
      humans.
AB  - Streptomycin is an aminoglycoside antibiotic with a well-known antituberculosis
      activity; it is commonly used in clinical practice because it is effective and
      cheap. However, streptomycin has severe ototoxic effects. The delayed and gradual
      onset may suggest that a metabolic derivative of the antibiotic could be a
      potential contributor to ototoxicity. As in a rat experimental model this
      compound was found to be streptidine, we investigated whether this ototoxic
      metabolite was also present in the blood of streptomycin-treated patients. To
      this end, we implemented and optimized a direct reverse-phase HPLC technique to
      identify and estimate streptomycin and streptidine in serum of streptomycin
      treated patients. All criteria for validation of the method were implemented in
      standard curves in serum of healthy non-treated volunteers by addition of
      increasing concentration of both compounds and their determination in a
      trichloroacetic acid deproteinized extract. We found that recovery of
      streptomycin or streptidine was > or =91.5%. Linearity was r(2)> or =0.99. The
      intraday and interday precisions were < or =9.7 and < or =10.6%, respectively.
      The relative intraday and interday error ranged from -9.0 to 8.3% for both
      compounds in human serum. Studies in patients included five male individuals
      treated from 35 to 90 days with 1g/day of streptomycin, presenting inner ear
      malfunction from mild to severe, in whose serum streptidine was always present,
      and could be successfully separated from streptomycin. Therefore, the validated
      method used can be a valuable tool to measure and follow these compounds in serum
      of streptomycin-treated patients.

PMID- 16956742
TI  - Clinical decision-making: Patients' preferences and experiences.
AB  - OBJECTIVE: To determine the congruence between patients' preferred style of
      clinical decision-making and the style they usually experienced and whether this
      congruence was associated with socio-economic status and/or the perceived quality
      of care provided by the respondent's regular doctor. METHODS: Cross-sectional
      survey of the American public using computer-assisted telephone interviewing.
      RESULTS: Three thousand two hundred and nine interviews were completed
      (completion rate 72%). Sixty-two percent of respondents preferred shared decision
      making, 28% preferred consumerism and 9% preferred paternalism. Seventy percent
      experienced their preferred style of clinical decision-making. Experiencing the
      preferred style was associated with high income (OR, 1.59; 95% CI, 1.16-2.16) and
      having a regular doctor who was perceived as providing excellent or very good
      care (OR, 2.39; 95% CI, 1.83-3.11). CONCLUSION: Both socio-economic status and
      having a regular doctor whom the respondent rated highly are independently
      associated with patients experiencing their preferred style of clinical decision
      making. PRACTICE IMPLICATIONS: Systems which promote continuity of care and the
      development of an on-going doctor-patient relationship may promote equity in
      health care, by helping patients experience their preferred style of clinical
      decision-making.

PMID- 16956743
TI  - Effect of a structured course involving goal management training in older adults:
      A randomised controlled trial.
AB  - OBJECTIVE: The objective of this study was to investigate the effects of a
      structured 6-week neuropsychological course on the executive functioning of older
      adults with cognitive complaints. METHODS: A randomised controlled design was
      used involving 69 community dwelling individuals aged 55 years and older. Both
      objective and subjective measures were included to assess executive functioning.
      General linear model with repeated measures analysis of variance was used to
      examine the intervention effects. RESULTS: After the intervention, the
      participants in the intervention group were significantly less annoyed by their
      cognitive failures, were better able to manage their executive failures and
      reported less anxiety symptoms than those in the waiting list control group.
      CONCLUSION: These findings indicate that a combination of psycho-education and
      training has the potential to change the attitude of older individuals towards
      their cognitive functioning. PRACTICE IMPLICATIONS: Because this training
      focussed on cognitive functions that are among the first to decline in older
      adults and the subjective evaluation of the people after training was quite
      favourable, the proposed intervention may be considered a valuable contribution
      to cognitive interventions for older adults.

PMID- 16956744
TI  - Role of progestin-induced mammary-derived growth hormone in the pathogenesis of
      cystic endometrial hyperplasia in the bitch.
AB  - Endogenous progesterone and synthetic progestins may induce hypersecretion of
      growth hormone (GH) of mammary origin, hyperplastic ductular changes in the
      mammary gland, and the development of cystic endometrial hyperplasia (CEH) in
      dogs. It was investigated whether progestin-induced mammary GH plays a role in
      the pathogenesis of CEH in the bitch. During 1 year, bitches with surgically
      excised mammary glands and healthy control bitches received medroxyprogesterone
      acetate (MPA). Before and after MPA treatment, uterine and mammary tissues were
      collected for histological, immunohistochemical, and RT-PCR examination. After
      MPA administration, the mammary tissue in the control dogs had differentiated
      into lobulo-alveolar structures and CEH was present in all uteri of both dog
      groups. In the MPA-exposed mammary tissue of the control dogs, GH could only be
      demonstrated immunohistochemically in proliferating epithelium. After treatment
      with MPA the dogs of both groups had immunohistochemically demonstrable GH in the
      cytoplasm of hyperplastic glandular uterine epithelial cells. RT-PCR analysis of
      the mammary gland tissue after MPA administration demonstrated a significant
      higher GH gene, and lower GHR gene expression than before treatment. In the
      uterus, the expression of the gene encoding for GH was significantly increased in
      the mastectomized dogs, whereas in the control dogs the expression of the gene
      encoding for insulin-like growth factor-I had significantly increased with MPA
      administration. MPA treatment significantly down regulated PR gene expression in
      the uterus in both dog groups. These results indicate that progestin-induced GH
      of mammary origin is not an essential component in the development of CEH in the
      bitch.

PMID- 16956746
TI  - Diethylhexyl phthalate impairs insulin binding and glucose oxidation in Chang
      liver cells.
AB  - The present study examined the dose-dependent effects of diethylhexyl phthalate
      (DEHP) on insulin receptor concentration and glucose oxidation in Chang liver
      cells. Chang liver cells (5 x 10(5) cells) were exposed to different
      concentrations (0, 50, 100, 200 and 400 microM) of DEHP for 24h. At the end of
      exposure, cells were utilized for assessing insulin receptor concentration and
      glucose oxidation. Both insulin receptor concentration and glucose oxidation in
      Chang liver cells were significantly reduced by high doses (200 and 400 microM)
      of phthalate exposure. The present study is first of its kind to report the
      direct adverse effects of DEHP on insulin receptor and glucose oxidation in Chang
      liver cells and suggests that DEHP exposure may have a negative influence on
      glucose homeostasis.

PMID- 16956745
TI  - Neonatal porcine endometrial development and epithelial proliferation affected by
      age and exposure to estrogen and relaxin.
AB  - In the pig, temporospatially regulated proliferation of uterine luminal (LE) and
      glandular (GE) epithelium between birth (postnatal day=PND 0) and PND 15 is
      essential for success of endometrial development. Exposure of gilts to estrogen
      (E) or relaxin (RLX) during this period disrupts uterine development, and
      neonatal E exposure can compromise adult uterine function. Neonatal uterotrophic
      effects of E and RLX, administered for 2 days beginning on PND 12, can be
      inhibited with the antiestrogen ICI 182,780 (ICI) indicating crosstalk between
      RLX and E signaling systems. Here, objectives were to determine effects of:
      (study 1) neonatal age and (study 2) exposure to E, RLX, and ICI on porcine
      neonatal uterine histoarchitecture and patterns of epithelial cell proliferation
      as reflected by proliferating cell nuclear antigen labeling index. In study 1,
      uteri were obtained on PND 0, 3, 6, 9, 12 and 15. Glandular epithelium, absent at
      birth, was observed by PND 3. Overall, epithelial labeling index increased from
      birth to PND 3, declined from PND 6-9 in LE and GE, and increased to PND 15 in
      GE. In study 2, uteri were collected on PND 14 after administration of vehicle,
      E, or RLX for 2 days, or following pretreatment with ICI. Alone, E was
      uterotrophic and adenogenic and increased labeling index in both LE and GE. Both
      RLX and ICI increased proliferation in GE. Effects of E and RLX were attenuated
      by ICI, providing further support for crosstalk between these signaling systems
      in the developing neonatal porcine endometrium.

PMID- 16956747
TI  - The selective effect of antipsychotics on the different dimensions of the
      experience of psychosis in schizophrenia spectrum disorders.
AB  - While most standard symptom scales regard the 'psychotic' or 'positive' dimension
      of schizophrenia as a single factor, several lines of evidence suggest that
      psychosis itself is a multidimensional phenomenon. The foregoing literature
      suggested at least five distinct dimensions to psychosis; to test this, we
      developed, validated and applied an instrument to measure these dimensions and
      then applied it to examine the effect of antipsychotics on the different
      dimensions of the psychotic experience. The Dimensions of Psychosis Instrument
      (DIPI) was administered to 91 psychotic patients with schizophrenia spectrum
      disorders and a confirmatory factor analyses (CFA) was carried out to examine the
      five dimensions: cognitive preoccupation (CP) with the psychotic experience;
      emotional involvement (EM); behavioural impact (BI) of the experience; conviction
      (CO) in it; emotional; and external perspective (EP) about the experience. In a
      separate cohort of 17 prospectively treated patients, the impact of
      antipsychotics on these dimensions was assessed. BI showed the greatest
      improvement (32%) at 2 weeks, while CP and emotional improved somewhat less (22%
      and 14%, respectively). Improvement in CO was limited (6%) while EP showed no
      change. These results suggest that over the first few weeks of treatment,
      antipsychotics rapidly reduce the behavioural impact of the principal psychotic
      symptom and decrease cognitive and emotional preoccupation with it, without
      greatly altering the patients' conviction in or perspective about their psychotic
      experience.

PMID- 16956748
TI  - Identification of novel cell-wall active antifungal compounds.
AB  - Fungal infections of humans and other animals are serious and often life
      threatening, especially in immunocompromised patients. One difficulty in treating
      fungal disease is the limited arsenal of antifungal compounds. The recent
      regulatory approval of three cell-wall active antifungal compounds encourages the
      search for additional clinical candidates that inhibit fungal cell wall
      formation. We have screened a small portion of a unique chemical library and have
      found eight compounds that appear to be inhibitors of fungal cell wall assembly.

PMID- 16956749
TI  - Evolution of resistance patterns and identification of risk factors for
      Streptococcus pneumoniae colonisation in daycare centre attendees in Athens,
      Greece.
AB  - Two cross-sectional surveillance studies were conducted during the winters of
      2000 and 2003 in Athens, Greece, to obtain nasopharyngeal swabs from healthy pre
      school children attending kindergartens. A total of 460 strains were examined in
      2000 and 485 strains in 2003, with carriage rates of 31.7% and 34.6%,
      respectively. Susceptibility patterns were evaluated for penicillin G,
      erythromycin, ceftriaxone, moxifloxacin, linezolid and telithromycin. Penicillin
      non-susceptibility increased from 20% to 34.9%, whereas erythromycin non
      susceptibility increased from 23% to 30.5%. Resistance to both agents climbed
      from 7.5% to 22.3% (P<0.001). No isolates were found to be resistant to any of
      the other antimicrobial agents. Risk factors for carriage and/or antimicrobial
      resistance were also assessed.

PMID- 16956750
TI  - Survey of extended-spectrum beta-lactamases in Escherichia coli isolates from a
      Portuguese hospital and characterisation of a novel class 1 integron (In60A)
      carrying the blaCTX-M-9 gene.
AB  - Between November 2001 and November 2004, 231 Escherichia coli isolates resistant
      to beta-lactam antibiotics were identified. In 14 isolates, bla(TEM-24) (2
      isolates), bla(TEM-52) (5 isolates) and bla(TEM-26) (7 isolates) were identified.
      In 145 E. coli isolates with the same M13 fingerprinting profile and the same
      resistance phenotype, the bla(CTX-M-15) gene was found in association with an
      insertion sequence ISEcp1. The bla(CTX-M-2) gene was identified in one E. coli
      isolate (290HSM), and in other E. coli isolate (246HSM) the bla(CTX-M-9) gene was
      contained in a new complex sul1-type class 1 integron (named In60A). This is the
      first report of three cefotaximases (CTX-M-15, CTX-M-2 and CTX-M-9) in E. coli
      isolates from a Portuguese hospital.

PMID- 16956751
TI  - Increased resistance to beta-lactams in a Klebsiella pneumoniae strain: role of a
      deletion downstream of the Pribnow box in the blaSHV-1 promoter.
AB  - Two hundred and five isolates of Klebsiella pneumoniae were collected from Nantes
      University Hospital in 2002. A new 30bp deletion was detected downstream of the 
      10 box of the SHV-1 promoter in a clinical K. pneumoniae isolate with a high
      amoxicillin/clavulanic acid minimum inhibitory concentration. Reverse
      transcription polymerase chain reaction revealed increased transcription of
      bla(SHV-1) mRNA. All conjugation mating assays failed. This new promoter was
      cloned upstream of the cat gene of the reporter plasmid pKK232-8 and compared
      with previously described bla(SHV-1) promoters. The deletion induced a 15-fold
      increase in promoter strength compared with the usual weak promoter. This study
      reports a new genetic event that increases bla(SHV-1) chromosomal gene
      expression, which may be of clinical relevance when associated with porin
      deficiency.

PMID- 16956752
TI  - ANKHD1, ankyrin repeat and KH domain containing 1, is overexpressed in acute
      leukemias and is associated with SHP2 in K562 cells.
AB  - In the present study, increased levels of ANKHD1 mRNA and protein expression in
      leukemia cell lines are reported, as compared with normal hematopoietic cells.
      Furthermore, a higher expression of ANKHD1 mRNA was detected in primary acute
      leukemia samples than in normal hematopoietic cells (P=0.002). ANKHD1 was
      detected in the cytosolic and membrane fraction of cells and was co
      immunoprecipitated with SHP2 in protein extracts of K562 and LNCaP cell lines.
      These findings suggest a role for ANKHD1 as a scaffolding protein that may be
      associated with the abnormal phenotype of leukemia cells.

PMID- 16956753
TI  - White matter integrity in kleptomania: a pilot study.
AB  - This study's goal was to examine microstructural organization of frontal white
      matter in kleptomania. Ten females with DSM-IV kleptomania and 10 female controls
      underwent diffusion tensor imaging. Inferior frontal white matter was the a
      priori region of interest. Trace and fractional anisotropy (FA) were also
      calculated for frontal and posterior cortical regions in both subject groups.
      Kleptomania subjects had significantly higher mean frontal Trace, and
      significantly lower mean frontal FA than control subjects. Group differences
      remained significant when right and left frontal Trace and FA were analyzed.
      Groups did not differ significantly in posterior Trace or FA. Kleptomania may be
      associated with decreased white matter microstructural integrity in inferior
      frontal brain regions.

PMID- 16956754
TI  - [Food allergy in children].
AB  - Food allergy is an adverse reaction to food protein by an immunological mechanism
      (IgE or non IgE-mediated). Signs can involve all organs, but atopic dermatitis
      remains the main manifestation. In children, only few allergens are involved. In
      France, it is cow milk, hen eggs, kiwi, peanut, fish, nuts, shrimp. Diagnosis is
      based on clinical history, skin tests, specific IgE and, sometimes, food
      challenge. Treatment is based on specific eviction. Regime can be total or
      sometimes limited to large among of the specific food, or only raw food. Food
      allergy disappears sometimes. Tolerance or food desensitization is in progress.

PMID- 16956755
TI  - From vagueness in medical thought to the foundations of fuzzy reasoning in
      medical diagnosis.
AB  - OBJECTIVE: This article delineates a relatively unknown path in the history of
      medical philosophy and medical diagnosis. It is concerned with the phenomenon of
      vagueness in the physician's "style of thinking" and with the use of fuzzy sets,
      systems, and relations with a view to create a model of such reasoning when
      physicians make a diagnosis. It represents specific features of medical ways of
      thinking that were mentioned by the Polish physician and philosopher Ludwik Fleck
      in 1926. The paper links Lotfi Zadeh's work on system theory before the age of
      fuzzy sets with system-theory concepts in medical philosophy that were introduced
      by the philosopher Mario Bunge, and with the fuzzy-theoretical analysis of the
      notions of health, illness, and disease by the Iranian-German physician and
      philosopher Kazem Sadegh-Zadeh. MATERIAL: Some proposals to apply fuzzy sets in
      medicine were based on a suggestion made by Zadeh: symptoms and diseases are
      fuzzy in nature and fuzzy sets are feasible to represent these entity classes of
      medical knowledge. Yet other attempts to use fuzzy sets in medicine were self
      contained. The use of this approach contributed to medical decision-making and
      the development of computer-assisted diagnosis in medicine. CONCLUSION: With
      regard to medical philosophy, decision-making, and diagnosis; the framework of
      fuzzy sets, systems, and relations is very useful to deal with the absence of
      sharp boundaries of the sets of symptoms, diagnoses, and phenomena of diseases.
      The foundations of reasoning and computer assistance in medicine were the result
      of a rapid accumulation of data from medical research. This explosion of
      knowledge in medicine gave rise to the speculation that computers could be used
      for the medical diagnosis. Medicine became, to a certain extent, a quantitative
      science. In the second half of the 20th century medical knowledge started to be
      stored in computer systems. To assist physicians in medical decision-making and
      patient care, medical expert systems using the theory of fuzzy sets and relations
      (such as the Viennese "fuzzy version" of the Computer-Assisted Diagnostic System,
      CADIAG, which was developed at the end of the 1970s) were constructed. The
      development of fuzzy relations in medicine and their application in computer
      assisted diagnosis show that this fuzzy approach is a framework to deal with the
      "fuzzy mode of thinking" in medicine.

PMID- 16956756
TI  - Manipulating proteins for neuroscience.
AB  - The design and manipulation of proteins has created many tools that have become
      popular in neurobiological studies, and new developments in protein science will
      be the fuel for future research. Genetically encoded protein-based biosensors
      have been developed with a wider range of sensing moieties, enabling detection of
      changes in localized protein synthesis, voltage, glutamate and/or glucose levels.
      Existing sensors, such as cameleon, have been modified and improved. Heterologous
      expression of Channelrhodopsin-2 and other light-gated methods for controlling
      cellular polarization enable action potentials to be non-invasively evoked,
      facilitating the study and modulation of behavior in intact animals. Finally, new
      methods in protein manipulation, including the site-specific incorporation of
      unnatural amino acids in vivo and the directed evolution of proteins, show
      promise in elucidating neural function with greater precision and flexibility.

PMID- 16956757
TI  - Basal lamina: Schwann cells wrap to the rhythm of space-time.
AB  - Schwann cells form myelin in the peripheral nervous system. All Schwann cells are
      surrounded by a basal lamina. Extracellular matrix molecules in the basal lamina,
      such as laminin, regulate key aspects of Schwann cell development including the
      formation, architecture and function of myelin. Recent genetic and cell
      biological experiments suggest that Schwann cells regulate the basal lamina and
      its receptors in both time and space, resulting in differential functions. These
      findings have important implications for diseases resulting from laminin
      dysfunction, such as congenital muscular dystrophy 1A.

PMID- 16956758
TI  - Rapid assessment breast clinics--evolution through audit.
AB  - This observational, cohort study aimed to examine the potential utility of Rapid
      Assessment Breast Clinics (RABC) beyond cancer detection at presentation. One
      thousand four hundred and twenty nine women were studied over an 18 month period.
      154 (10.7%) had breast cancer - 87.7% of whom were seen expediently with 92.9%
      being diagnosed at one attendance. One hundred and forty three (10%) of those
      with a benign diagnosis were found by routine questioning to have significant
      familial risk separate to their reason for referral. Despite careful triage,
      considerable contamination of appointment allotment occurred with many who were
      correctly triaged as non-urgent being seen 'urgently'. One hundred and seventy
      six attendees (12.3%) had neither the symptom that triggered referral, nor breast
      lump, nipple discharge nor family history of breast cancer, while 283 (19.8%) had
      no objective clinical or radiological abnormality. Although RABC reliably
      categorise malignant versus non-malignant diagnoses despite cluttering by low
      risk women, a significant proportion of non-cancer patients still require address
      of future risk rather than reassurance of their present status alone.

PMID- 16956759
TI  - Treatment of high risk medulloblastomas in children above the age of 3 years: a
      SFOP study.
AB  - AIM: Improvement of EFS of children older than 3 years with high risk
      medulloblastoma. METHODS: Between 1993 and 1999, 115 patients (3-18 years, mean 8
      years) with high risk medulloblastoma were included. After surgery treatment
      consisted of chemotherapy ('8in1' and etoposide/carboplatin) before and after
      craniospinal radiotherapy. RESULTS: Patients were staged using Chang-criteria (PF
      residue only, M1 and M2/M3) by local investigator as well as by central review
      panel (82.4% concordance). Chemotherapy was well tolerated without major delays
      in radiotherapy. With a mean follow up of 81 months (9-119), 5-year EFS was 49.8%
      and OS 60.1%. In detail according to subgroups EFS was 68.8% for PF residue only,
      58.8% for M1 disease and 43.1% for M2/M3. CONCLUSION: M1 patients are legitimate
      high risk patients. Survival rates are still very low for high risk
      medulloblastoma patients and future trials should therefore focus on more
      intensive (chemotherapy/radiotherapy) treatment.

PMID- 16956761
TI  - Molecular detection of EGFRvIII-positive cells in the peripheral blood of breast
      cancer patients.
AB  - The aim of this study is to evaluate epidermal growth factor receptor variant
      III, EGFRvIII, a cancer specific mutant, as a possible marker for the diagnosis
      of breast cancer occult systemic disease. EGFRvIII mRNA was identified by an RT
      nested PCR with a high sensitivity. In 102 women studied, the mutant was detected
      in the peripheral blood of 30% of 33 low risk, early stage patients, in 56% of 18
      patients selected for neoadjuvant chemotherapy, in 63.6% of 11 patients with
      disseminated disease and 0% of 40 control women. In low risk, early stage
      patients, the presence of one or more tumour characteristics predicting
      recurrence such as the absence of oestrogen receptors and the presence of ERBB2
      or histologic grades G2/G3 was significantly associated with EFGRvIII detection
      (p<0.05). EGFRvIII mRNA has characteristics to be a useful marker for the
      diagnosis of occult systemic disease in breast cancer. Follow-up studies will
      evaluate its clinical value as a decision criterion for systemic therapy.

PMID- 16956760
TI  - Evaluations of vascular disrupting agents CA4P and OXi4503 in renal cell
      carcinoma (Caki-1) using a silicon based microvascular casting technique.
AB  - The present study evaluated the treatment efficacy of the vascular disrupting
      agents CA4P and OXi4503 in an orthotopically transplanted human renal cell
      carcinoma xenograft model (Caki-1). Experiments used vascular casting, vessel
      density assessments as well as tumour necrosis measurements to evaluate the
      efficacy of these agents. After treatment with either agent, assessment of the
      vascular casts showed an almost total eradication of tumour blood vessels.
      Histological evidence further supported this observation, showing extensive
      central tumour necrosis with only a small viable rim of tumour cells remaining at
      the periphery. These results suggest that vascular disrupting agents CA4P and
      OXi4503 may have utility in the treatment of renal cell carcinoma, an encouraging
      result given that current conventional therapies have been currently largely
      unsuccessful in managing this disease.

PMID- 16956762
TI  - Insights into COPI coat assembly and function in living cells.
AB  - Eukaryotic cells use an elaborate machinery involving the COPI coat complex to
      control protein trafficking in the secretory pathway. Although individual
      components of this complex are well known and their roles in deforming lipid
      membranes into coated carriers are well described, the precise sequence of
      molecular events by which these components assemble into and release from the
      COPI coat lattice remains unclear. Here, we present images and movies
      characterizing the dynamics of protein components of the COPI coat in living
      cells. We discuss the self-assembly of these coat components into a molecular
      machine for sorting and trafficking membranes.

PMID- 16956763
TI  - Step-cut tibial tubercle osteotomy for access in revision total knee replacement.
AB  - In this retrospective cohort, the results of step-cut tibial tubercle osteotomy
      (TTO) in 39 revision total knee arthroplasty, using the Continuum Knee System
      (CKS), are determined. In 39 revision, total knee arthroplasties, adequate
      exposure was obtained after step-cut TTO. All knees were recently reviewed for
      clinical and radiological results. Symptomatic TTO-related complications occurred
      in three out of 39 patients. Two patients had proximal migration of the tibial
      tubercle due to an insufficient step-cut. Another patient had posttraumatic
      avulsion of the tibial tubercle. No TTO-related extensor lag or tibial fracture
      occurred We conclude that, when adequate exposure cannot be obtained, step-cut
      TTO is a safe and reproducible procedure if strict attention is paid to technique
      and fixation. It does not compromise the functional results of TKA.

PMID- 16956764
TI  - Dislocation of posterior-stabilized mobile-bearing knee prosthesis. A case
      report.
AB  - Spin-out of mobile-bearing knees is a significant early complication of mobile
      bearing total knee arthroplasty. Dislocation of the cam-post mechanism of fixed
      bearing posterior-stabilized knees occurs more rarely. We have observed an
      unusual case of dislocation of posterior-stabilized rotating-platform total knee
      arthroplasty, which has both a cam-post mechanism and rotating platform. A 65
      year-old man with knee osteoarthritis and cervical spondylotic myelopathy
      underwent total knee arthroplasty using a mobile-bearing prosthesis. The
      dislocation, which occurred 4 days postoperatively, could not be reduced by
      closed manipulation. However, spontaneous reduction occurred 6 days after the
      dislocation, which did not recur. A gap mismatch or trapezoidal-shaped gaps may
      lead to dislocation or spin-out of the bearing insert. This case illustrates that
      dislocation of a posterior-stabilized mobile-bearing total knee arthroplasty can
      occur, and both quadriceps deficiency and ligament laxity may contribute to the
      risk of dislocation.

PMID- 16956765
TI  - Coherent super-resolution microscopy via laterally structured illumination.
AB  - Theory describing a super-resolution microscopy experiment using temporally and
      spatially coherent structured illumination was developed, and used to derive a
      method for processing experimental data. Numerical simulations were performed to
      verify that the method can, in principle, produce super-resolved images that are
      exactly equivalent to an image processed by a system with a much larger aperture
      (that is, the correct weighting between different regions of the image spectrum
      is maintained). The process was then demonstrated experimentally, showing a
      factor of two improvement in resolution over a diffraction-limited, coherently
      illuminated, microscope.

PMID- 16956766
TI  - Pneumococcal meningitis causes accumulation of neurotoxic kynurenine metabolites
      in brain regions prone to injury.
AB  - Pneumococcal meningitis (PM) is characterized by an intense inflammatory host
      reaction that contributes to the development of cortical necrosis and hippocampal
      apoptosis. Inflammatory conditions in the brain are known to induce tryptophan
      degradation along the kynurenine pathway, resulting in accumulation of neurotoxic
      metabolites. In the present study, we investigated the contribution of the
      kynurenine pathway to brain injury in experimental PM by measuring the
      concentration of its metabolites and the enzymatic activities and mRNA levels of
      its major enzymes in the vulnerable brain regions. In the late phase of acute PM,
      we found a significant transcriptional upregulation of kynurenine-3-hydroxylase
      and an accumulation of the neurotoxic metabolites 3-hydroxykynurenine (3-HKYN)
      and 3-hydroxyanthranilic acid in cortex and hippocampus. The positive correlation
      between the concentration of 3-HKYN and the extent of hippocampal apoptosis adds
      support to the concept that 3-HKYN contributes to brain injury in PM.

PMID- 16956767
TI  - Loss of M5 muscarinic acetylcholine receptors leads to cerebrovascular and
      neuronal abnormalities and cognitive deficits in mice.
AB  - The M5 muscarinic acetylcholine receptor (M5R) has been shown to play a crucial
      role in mediating acetylcholine-dependent dilation of cerebral blood vessels. We
      show that male M5R-/- mice displayed constitutive constriction of cerebral
      arteries using magnetic resonance angiography in vivo. Male M5R-/- mice exhibited
      a significantly reduced cerebral blood flow (CBF) in the cerebral cortex,
      hippocampus, basal ganglia, and thalamus. Cortical and hippocampal pyramidal
      neurons from M5R-/- mice showed neuronal atrophy. Hippocampus-dependent spatial
      and nonspatial memory was also impaired in M5R-/- mice. In M5R-/- mice, CA3
      pyramidal cells displayed a significantly attenuated frequency of the spontaneous
      postsynaptic current and long-term potentiation was significantly impaired at the
      mossy fiber-CA3 synapse. Our findings suggest that impaired M5R signaling may
      play a role in the pathophysiology of cerebrovascular deficits. The M5 receptor
      may represent an attractive novel therapeutic target to ameliorate memory
      deficits caused by impaired cerebrovascular function.

PMID- 16956768
TI  - Which is more appropriate for right axillary artery cannulation in acute type A
      aortic dissection--directly or with graft?

PMID- 16956770
TI  - A web-based study concept designed to progress clinical research for 'orphan'
      disease areas in haematological oncology in the elderly: the SHIELD programme.
AB  - Clinical randomised trials (RCT) in elderly populations with haematological
      malignant disease are rare and difficult to perform. This paper describes the
      methodology and process of organising an internet-based international programme
      for Hodgkin's lymphoma in the >60 years age group in a format which is compliant
      with the European Clinical Trials Directive (EUCTD). International agreement was
      obtained on the need for a web-based data collection system for basic
      registration and evaluation which incorporated an electronic case report system
      (eCRF) for a Phase II Study. Objective assessments of co-morbidity, activities of
      daily living (ADL) and instruments of daily living (IADL) were built-in to define
      objective frailty, linked to physician treatment choice or inclusion on the Study
      protocol. The programme is now operating effectively in the UK and Germany and
      provides an organisational model of how research in 'orphan' disease areas of
      haematological and solid tumour oncology, previously considered very difficult,
      might be overcome.

PMID- 16956771
TI  - Obesity and cancer risk: the role of the insulin-IGF axis.
AB  - Accumulating epidemiological evidence shows that being either overweight or
      obese, in other words having excess body weight (EBW), is associated with an
      increased risk of several, common, adult cancers. The molecular mechanisms that
      underlie these associations are not understood fully, but insulin resistance is
      likely to be important. The insulin-cancer hypothesis postulates that chronic
      hyperinsulinemia is associated with decreased concentrations of insulin-like
      growth factor binding protein1 (IGFBP-1) and IGFBP-2, leading to increased
      availability of IGF-I and concomitant changes in the cellular environment that
      favor tumor formation. However, the situation is likely to be more complex
      because hyperinsulinemia is also associated with alterations in related molecular
      systems (e.g. sex steroids and adipocytokines). As the prevalence of EBW
      increases to epidemic proportions, untangling the links between EBW and the
      insulin-IGF axis and its wider molecular interactions will become increasingly
      important in the development of preventive strategies.

PMID- 16956772
TI  - Shared and distinct neural correlates of singing and speaking.
AB  - Using a modified sparse temporal sampling fMRI technique, we examined both shared
      and distinct neural correlates of singing and speaking. In the experimental
      conditions, 10 right-handed subjects were asked to repeat intoned ("sung") and
      non-intoned ("spoken") bisyllabic words/phrases that were contrasted with
      conditions controlling for pitch ("humming") and the basic motor processes
      associated with vocalization ("vowel production"). Areas of activation common to
      all tasks included the inferior pre- and post-central gyrus, superior temporal
      gyrus (STG), and superior temporal sulcus (STS) bilaterally, indicating a large
      shared network for motor preparation and execution as well as sensory
      feedback/control for vocal production. The speaking more than vowel-production
      contrast revealed activation in the inferior frontal gyrus most likely related to
      motor planning and preparation, in the primary sensorimotor cortex related to
      motor execution, and the middle and posterior STG/STS related to sensory
      feedback. The singing more than speaking contrast revealed additional activation
      in the mid-portions of the STG (more strongly on the right than left) and the
      most inferior and middle portions of the primary sensorimotor cortex. Our results
      suggest a bihemispheric network for vocal production regardless of whether the
      words/phrases were intoned or spoken. Furthermore, singing more than humming
      ("intoned speaking") showed additional right-lateralized activation of the
      superior temporal gyrus, inferior central operculum, and inferior frontal gyrus
      which may offer an explanation for the clinical observation that patients with
      non-fluent aphasia due to left hemisphere lesions are able to sing the text of a
      song while they are unable to speak the same words.

PMID- 16956773
TI  - Tuning of the human left fusiform gyrus to sublexical orthographic structure.
AB  - Neuropsychological and neurophysiological evidence point to a role for the left
      fusiform gyrus in visual word recognition, but the specific nature of this role
      remains a topic of debate. The aim of this study was to measure the sensitivity
      of this region to sublexical orthographic structure. We measured blood
      oxygenation (BOLD) changes in the brain with functional magnetic resonance
      imaging while fluent readers of English viewed meaningless letter strings. The
      stimuli varied systematically in their approximation to English orthography, as
      measured by the probability of occurrence of letters and sequential letter pairs
      (bigrams) comprising the string. A whole-brain analysis showed a single region in
      the lateral left fusiform gyrus where BOLD signal increased with letter sequence
      probability; no other brain region showed this response pattern. The results
      suggest tuning of this cortical area to letter probabilities as a result of
      perceptual experience and provide a possible neural correlate for the 'word
      superiority effect' observed in letter perception research.

PMID- 16956774
TI  - Improved segmentation reproducibility in group tractography using a quantitative
      tract similarity measure.
AB  - The field of tractography is rapidly developing, and many automatic or
      semiautomatic algorithms have now been devised to segment and visualize neural
      white matter fasciculi in vivo. However, these algorithms typically need to be
      given a starting location as input, and their output can be strongly dependent on
      the exact location of this "seed point". No robust method has yet been devised
      for placing these seed points so as to segment a comparable tract in a group of
      subjects. Here, we develop a measure of tract similarity, based on the shapes and
      lengths of the two tracts being compared, and apply it to the problem of
      consistent seed point placement and tract segmentation in group data. We
      demonstrate that using a single seed point transferred from standard space to
      each native space produces considerable variability in tractography output
      between scans. However, by seeding in a group of nearby candidate points and
      choosing the output with the greatest similarity to a reference tract chosen in
      advance--a method we refer to as neighborhood tractography--this variability can
      be significantly reduced.

PMID- 16956775
TI  - The effect of visuospatial attentional load on the processing of irrelevant
      acoustic distractors.
AB  - This work investigated the role of cognitive control functions in selective
      attention when task-relevant and -irrelevant stimuli come from different sensory
      modalities. We parametrically manipulated the load of an attentive tracking task
      and investigated its effect on irrelevant acoustic change-related processing.
      While subjects were performing the visual attentive tracking task, event-related
      potentials (ERPs) were recorded for frequent standard tones and rare deviant
      tones presented as auditory distractors. The deviant tones elicited two change
      related ERP components: the mismatch negativity (MMN) and the P3a. The amplitude
      of the MMN, which indexes the early detection of irregular changes, increased
      with increasing attentional load, whereas the subsequent P3a component, which
      indicates the involuntary orienting of attention to deviants, was significant
      only in the lowest load condition. These findings suggest that active exclusion
      of the early detection process of irrelevant acoustic changes depends on
      available resources of cognitive control, whereas the late involuntary orienting
      of attention to deviants can be passively suppressed by high demand on central
      attentional resources. The present study thus reveals opposing visual attentional
      load effects at different temporal and functional stages in the rejection of
      deviant auditory distractors and provides a new perspective on the resolution of
      the long-standing early versus late attention selection debate.

PMID- 16956776
TI  - Onset of epilepsy and menarche--is there any relationship?
AB  - PURPOSE: Women with epilepsy have increased frequency of reproductive health
      problems compared to women without epilepsy. In puberty, reproductive hormonal
      changes during sexual maturation may affect epilepsy and induce the debut of
      seizures as indicated in some studies. On the other hand, epileptic activity
      affects sex hormone function, which may induce alterations in pubertal endocrine
      maturation and thereby menarche age. We wanted to investigate the relation
      between epilepsy and menarche age in a larger population of female epilepsy
      patients. METHODS: A retrospective, questionnaire study of a cohort of 265 female
      outpatients from three Norwegian hospitals and 142 controls, aged 18-45 years was
      conducted. Parameters regarding epilepsy and reproductive health issues were
      registered. Perimenarche was defined as 2 years before and 2 years after the year
      of menarche. RESULTS: There was a significantly higher frequency of patients with
      epilepsy debut between 10 and 18 year compared to 0-9 years (p<0.01). There was,
      however, no significant difference in occurrence of epilepsy debut in the
      perimenarche period compared to the 5 year periods before and after perimenarche,
      and no significant difference in epilepsy debut in the year of menarche compared
      to the 5 years before or after. Menarche age was not significantly different in
      those with epilepsy debut before or after menarche. Epilepsy type (idiopathic
      generalised or partial) did not influence the menarche age. CONCLUSIONS: The
      study did not confirm the former observations of clustering of epilepsy debut at
      menarche or in the perimenarche period or alterations in menarche age in girls
      with epilepsy. However, onset of epilepsy is more frequent in the adolescent
      years (10-18), than in childhood (0-9).

PMID- 16956778
TI  - Does a pleiotropic gene explain deafness and blue irises in white cats?
AB  - The prevalence of deafness is high in cat populations in which the dominant white
      gene is segregating. The objective of this study was to investigate whether there
      is a gene that is responsible for deafness as well as for blue eyes and to
      establish a plausible mode of inheritance. For this purpose, data from an
      experimental colony with deaf cats were analyzed. The hearing status was
      determined by acoustically evoked brain stem responses (BAER). Complex
      segregation analyses were conducted to find out the most probable mode of
      inheritance using maximum likelihood procedures. The prevalence of deafness and
      partial hearing in the experimental colony was 67% and 29%, respectively. The
      results of the bivariate segregation analysis support the hypothesis of a
      pleiotropic major gene segregating for deafness and blue iris colour. The high
      heritability coefficients for both traits, 0.55 and 0.75 respectively, indicate
      that beside the major gene there is an important influence of polygenic effects.

PMID- 16956777
TI  - Serotypes, virulence genes, intimin types and PFGE profiles of Escherichia coli
      isolated from piglets with diarrhoea in Slovakia.
AB  - Two hundred and fifty Escherichia coli isolates from diarrhoeic and healthy
      piglets were serotyped and tested for the presence of virulence genes for
      fimbriae, intimin, heat-labile (LT) and heat-stable (STa and STb) enterotoxins,
      Stx toxins, and enteroaggregative heat-stable 1 (EAST1) enterotoxin by polymerase
      chain reaction (PCR). Although 220 isolates from diarrhoeic piglets belonged to
      43 O serogroups and 77 O:H serotypes, 60% were of one of the 10 serogroups O2,
      O8, O15, O54, O84, O101, O141, O147, O149 and O157, and 60% belonged to only 10
      serotypes (O8:H-, O54:H-, O84:H7, O101:H-, O141:H-, O141:H4, O147:H-, O149:H10,
      O163:H-, and ONT:H-). PCR showed that 79% of 220 isolates carried genes for at
      least one of the virulence factors tested. The gene encoding for EAST1 was the
      most prevalent (65%) followed by those encoding for STb (49%), LT (42%), STa
      (13%), and Stx2e (4%). Eighty-three (38%) of the 220 E. coli isolates carried the
      gene for F4 (K88), whereas genes for F18, F5 (K99), F41, F6 (P987), F17, and
      intimin (eae) were detected in 9%, 3%, 3%, 3%, 1%, and 3%, respectively.
      Seropathotype O149:H10:F4:LT/STb/EAST1 (70 isolates) was the most common,
      representing 32% of isolates. Pulsed-field gel electrophoresis (PFGE) analysis
      with XbaI of 15 O149:H10 representative isolates from diarrhoeic piglets
      distinguished 14 types. The 15 isolates exhibited a wide variability of distinct
      restriction patterns though all belonged to the same serotype (O149:H10), and all
      but one showed identical virulence determinants (F4, LT, STb, and EAST1). Among
      30 isolates from healthy piglets only two virulence genes were detected: EAST1
      (26%) and eae (17%). In total, 12 isolates were positives for the eae gene: five
      isolates had intimin beta1, four possessed intimin theta and three showed intimin
      type xiB. This is believed to be the first study describing the presence of
      intimin type xiB in E. coli of porcine origin.

PMID- 16956779
TI  - The use of vaccines to control disease is not a simple matter.

PMID- 16956780
TI  - Detection and distribution of apoptotic cell death in normal and diseased canine
      cranial cruciate ligaments.
AB  - One of the possible initiating factors in canine cranial cruciate ligament (CCL)
      rupture could be an abnormal pattern of ligament cell death. This study compared
      apoptotic cell death in sections of ruptured CCLs and normal controls, and
      examined nitric oxide (NO) production in joint tissues and correlated this to
      apoptosis. CCLs and cartilage from the lateral femoral condyle were harvested
      from 10 healthy dogs and 15 dogs with CCL rupture and ligaments were further
      processed to detect cleaved caspase-3 and to determine supernatant NO production
      in explant cultures. Apoptotic activity was greater in ruptured ligaments
      compared to controls. NO in ligaments showed a moderate but significant positive
      correlation with caspase-positive cells. The results suggest that increased
      apoptosis has a role in CCL rupture and that apoptosis may be influenced by local
      NO production.

PMID- 16956781
TI  - [Use of prosthetic materials in reconstructive pelvic floor surgery. An evidence
      based analysis. Gynecol Obstet Fertil 2006;34:292-97].

PMID- 16956782
TI  - [Decreased fetal movements in the third trimester: what to do? Gynecol Obstet
      Fertil 2005;33:861-869].

PMID- 16956783
TI  - Evaluation of repeatability of pressure algometry on the neck muscles for
      clinical use.
AB  - Neck and shoulder pain is a common disorder which is often associated with a low
      pressure pain threshold (PPT) of muscle tissues as manifested by hyperalgesia on
      palpation or the use of a pressure algometer. The objective of the present study
      was to evaluate the intratester repeatability of pressure algometer (Force-Five)
      on the neck and shoulder area in women with neck pain. The study was cross
      sectional with single-group repeated measurements. PPT measurements in 20 women
      with chronic non-specific neck pain were measured on consecutive days at the
      levator scapulae, at two points on the trapezius muscles on each side and at the
      sternum as the only non-muscular site. The intratester repeatability of the PPT
      measurements was satisfactory or good (Intraclass correlation coefficient (ICC
      0.78-0.93). The coefficient of repeatability ranged from 16.8 to 24.4N/cm2 and
      the coefficient of variation ranged from 10% to 22%, depending on the site
      tested. Considerable individual variation was observed when consecutive measures
      were analysed against their mean. On the group level the repeatability of the
      measurements allows the pressure algometer to be used for research purposes.
      However, on the individual level, due to the considerable variation found in the
      PPT results, caution is advised when interpreting the results in clinical
      practice.

PMID- 16956784
TI  - Autoluminescence imaging: a non-invasive tool for mapping oxidative stress.
AB  - Living organisms spontaneously emit faint light, and this autoluminescence is
      stimulated in response to many stresses. This phenomenon is attributable to the
      endogenous production of excited states during oxidative reactions, particularly
      during peroxidation of lipids, which generates light-emitting molecules such as
      triplet carbonyls and singlet oxygen. Using highly sensitive cameras, it is now
      possible to remotely image spontaneous luminescence with a good spatial
      resolution, providing a new non-invasive tool for mapping oxidative stress and
      lipid peroxidation in plants.

PMID- 16956785
TI  - Electronic and fluorescence spectral studies of a novel porphyrin-polypyridyl
      ruthenium(II) hybrid linked by a butyl chain.
AB  - The electronic and fluorescence spectroscopic properties of a novel porphyrin
      polypyridyl ruthenium(II) hybrid, [C(4)-TPP-(ip)Ru(phen)(2)](ClO(4))(2)
      (TPP=5,10,15,20-tetraphenylporphyrin, ip=imidazo[4,5-f][1,10]phenanthroline and
      phen=1,10-Phenanthroline), in which a polypyridyl ruthenium(II) moiety is linked
      to a porphyrin moiety by a butyl chain have been investigated and compared to its
      corresponding reference compounds. The studies of electronic absorption spectra
      have shown that there is an electronic interaction between the porphyrin moiety
      and the polypyridyl ruthenium(II) moiety in the hybrid. It can be found that
      intramolecular photoinduced electron and energy transfer processes may occur in
      the hybrid from the fluorescence spectra. When exciting in Soret band and Q band
      of porphyrin, the fluorescence quenching of the porphyrin moiety of the hybrid
      takes place due to electron transfer from the lowest singlet excited state (S(1))
      to the appended polypyridyl rutherium(II) moiety, while the decay of S(2) (the
      second-excited singlet state) of the porphyrin moiety is mainly contributed to
      internal conversion to S(1). When exciting in MLCT band of the polypyridyl
      ruthenium(II) moiety, fluorescence corresponding to the polypyridyl ruthenium(II)
      moiety is quenched by intramolecular energy transfer from (3)MLCT of the
      ruthenium moiety to the lowest-energy triplet state localized on the porphyrin
      moiety.

PMID- 16956786
TI  - Infrared and DNA-binding on ultraviolet and fluorescence spectra of new copper
      and zinc complexes with a naringenin Schiff-base ligand.
AB  - A naringenin Schiff-base ligand (H(3)L) and its copper(II) and zinc(II) complexes
      have been synthesized and characterized by elemental analyses, molar
      conductivities, (1)H NMR, IR spectra, UV spectra and thermal analyses. The DNA
      binding properties of the Cu(II) and Zn(II) complexes have been investigated by
      fluorescence spectroscopy, ultraviolet spectroscopy and by viscosity
      measurements. The results indicate that complexes and ligand may bind to DNA by
      intercalation modes, but the binding affinity of the complexes is much higher
      than that of the ligand.

PMID- 16956787
TI  - Spectroscopic study of association of a hemicyanine dye in mixed aqueous binary
      solvents.
AB  - Electronic absorption and steady state emission properties of a hemicyanine dye
      [4-[4-(dimethylamino)styryl]-1-docosylpyridinium bromide], have been studied in
      several pure solvents and two mixed binary solvents (water+ethanol and
      water+acetonitrile). In pure solvents the band-width of the absorption spectrum
      correlates well with the Stoke's shift. In mixed aqueous solvents two different
      molecular forms of the solute, viz. the monomer and the dimer of the solute
      exists in equilibrium. Thermodynamic parameters (e.g. the Delta G degrees and
      Delta H degrees ) characterizing the equilibrium have been determined. While the
      value of Delta G degrees changes very slightly with the composition of the binary
      mixture, the value of Delta H degrees has been observed to depend significantly
      with solvent composition.

PMID- 16956788
TI  - Coordination properties of tridentate (N,O,O) heterocyclic alcohol (PDC) with
      Cu(II). Mixed ligand complex formation reactions of Cu(II) with PDC and some bio
      relevant ligands.
AB  - The formation equilibria of copper(II) complexes and the ternary complexes
      Cu(PDC)L (PDC=2,6-bis-(hydroxymethyl)-pyridine, HL=amino acid, amides or DNA
      constituents) have been investigated. Ternary complexes are formed by a
      simultaneous mechanism. The results showed the formation of Cu(PDC)L, Cu(PDC, H(
      1))(L) and Cu(PDC, H(-2))(L) complexes. The concentration distribution of the
      complexes in solution is evaluated as a function of pH. The effect of dioxane as
      a solvent on the protonation constant of PDC and the formation constants of
      Cu(II) complexes are discussed. The thermodynamic parameters DeltaH degrees and
      DeltaS degrees calculated from the temperature dependence of the equilibrium
      constants are investigated.

PMID- 16956789
TI  - Spatial and chronological differences in hepatitis B virus genotypes from
      patients with acute hepatitis B in Japan.
AB  - Genotypes of hepatitis B virus (HBV) were determined in 485 patients with acute
      hepatitis B from all over Japan. They were A in 92 (19%), Ba in 26 (5%), Bj in 32
      (7%), C in 330 (68%) and D in 5 (1%). Sexual contacts were the main route of
      transmission in them. Overall, HBV persisted in only 5 of the 464 (1%) followed
      patients. Genotypes C accounted for more than 68% in northern as well as southern
      areas, contrasting with genotype A accounting for 34% in and around the
      Metropolitan areas. During 24 years from 1982 to 2005, genotype A increased from
      5% to 33%, while genotype B gradually decreased from 26% to 8%. Fulminant
      hepatitis was significantly more frequent in infection with genotype Bj (41%)
      than those with the other genotypes (p<0.01). The core-promoter double mutation
      (T1762/A1764) and precore stop-codon mutation (A1896) were more frequent in
      patients with fulminant than acute self-limited hepatitis (57% versus 15% and 58%
      versus 10%, respectively, p<0.01 for both). In conclusion, genotype A distributes
      unevenly over Japan, prevails in younger patients through sexual transmission and
      has increased with years. Furthermore, fulminant outcome was more frequent in
      patients with genotype Bj than those with the other genotypes.

PMID- 16956791
TI  - Spontaneous development of otitis media in plasminogen-deficient mice.
AB  - Inflammatory conditions of the ear, otitis media, are one of the most common
      disease entities in children. In this study, the role of the plasminogen
      (plg)/plasmin system for the spontaneous development of chronic otitis media was
      investigated by the analysis of plg-deficient mice. Whereas essentially all of
      the wild-type control mice kept a healthy status of the middle ear, all the plg
      deficient mice gradually developed chronic otitis media with various degrees of
      inflammatory changes during an 18-week observation period. Five bacterial strains
      were identified in materials obtained from the middle ear cavities of six plg
      deficient mice. Morphological studies revealed the formation of an amorphous mass
      tissue and inflammatory changes in the middle ears of plg-deficient mice.
      Immunohistochemical studies further indicate a mass infiltration of neutrophils
      and macrophages as well as the presence of T and B cells in the middle ear mucosa
      of these mice. Extensive fibrin deposition and an abnormal keratin formation were
      also observed in the tympanic membrane, the middle ear cavity and external ear
      canal in these mice. These results suggest that plg plays an essential role in
      protecting against the spontaneous development of chronic otitis media. Our
      findings also suggest the possibility of using plg for clinical therapy of
      certain types of otitis media.

PMID- 16956790
TI  - Homologous desensitization of signalling by the beta (beta) isoform of the human
      thromboxane A2 receptor.
AB  - Thromboxane (TX) A(2) is a potent stimulator of platelet activation/aggregation
      and smooth muscle contraction and contributes to a variety of pathologies within
      the vasculature. In this study, we investigated the mechanism whereby the
      cellular responses to TXA(2) mediated through the TPbeta isoform of the human
      TXA(2) receptor (TP) are dynamically regulated by examining the mechanism of
      agonist-induced desensitization of intracellular signalling and second messenger
      generation by TPbeta. It was established that TPbeta is subject to profound
      agonist-induced homologous desensitization of signalling (intracellular calcium
      mobilization and inositol 1,3,5 trisphosphate generation) in response to
      stimulation with the TXA(2) mimetic U46619 and this occurs through two key
      mechanisms: TPbeta undergoes partial agonist-induced desensitization that occurs
      through a GF 109203X-sensitive, protein kinase (PK)C mechanism whereby Ser(145)
      within intracellular domain (IC)(2) has been identified as the key phospho
      target. In addition, TPbeta also undergoes more profound and sustained agonist
      induced desensitization involving G protein-coupled receptor kinase (GRK)2/3
      phosphorylation of both Ser(239) and Ser(357) within its IC(3) and carboxyl
      terminal C-tail domains, respectively. Inhibition of phosphorylation of either
      Ser(239) or Ser(357), through site directed mutagenesis, impaired desensitization
      while mutation of both Ser(239) and Ser(357) almost completely abolished
      desensitization of signalling, GRK phosphorylation and beta-arrestin association,
      thereby blocking TPbeta internalization. These data suggest a model whereby
      agonist-induced PKC phosphorylation of Ser(145) partially impairs. TPbeta
      signalling while GRK2/3 phosphorylation at both Ser(239) and Ser(357) within its
      IC(3) and C-tail domains, respectively, sterically inhibits G-protein coupling,
      profoundly desensitizing signalling, and promotes beta-arrestin association and,
      in turn, facilitates TPbeta internalization. Thromboxane (TX) A(2) is a potent
      stimulator of platelet aggregation and smooth muscle contraction and contributes
      to a variety of vascular pathologies. Herein the mechanism whereby the cellular
      responses to TXA(2) mediated through the TPbeta isoform of the human TXA(2)
      receptor (TP) are dynamically regulated was investigated by examining the
      mechanism of its agonist-induced desensitization of intracellular signalling and
      second messenger generation. TPbeta is subject to profound agonist-induced
      homologous desensitization of signalling (intracellular calcium mobilization and
      inositol 1,3,5 trisphosphate generation) in response to stimulation with the
      TXA(2) mimetic U46619 and this occurs through two key mechanisms: TPbeta
      undergoes partial agonist-induced desensitization that occurs through a GF
      109203X-sensitive, protein kinase (PK)C mechanism whereby Ser(145) within
      intracellular domain (IC)(2) was identified as the key phospho-target. In
      addition, TPbeta also undergoes more profound and sustained agonist-induced
      desensitization involving G protein-coupled receptor kinase (GRK)2/3
      phosphorylation of both Ser(239) and Ser(357) within its IC(3) and carboxyl
      terminal C-tail domains, respectively. Inhibition of phosphorylation of either
      Ser(239) or Ser(357), through site directed mutagenesis, impaired desensitization
      while mutation of both Ser(239) and Ser(357) almost completely abolished
      desensitization of signalling, GRK phosphorylation and beta-arrestin association,
      thereby blocking TPbeta internalization. These data suggest a model whereby
      agonist-induced PKC phosphorylation of Ser(145) partially impairs TPbeta
      signalling while GRK2/3 phosphorylation at both Ser(239) and Ser(357) within its
      IC(3) and C-tail domains, respectively, sterically inhibits G-protein coupling,
      profoundly desensitizing signalling, and promotes beta-arrestin association and,
      in turn, facilitates TPbeta internalization.

PMID- 16956792
TI  - Outbreak detection and secondary prevention of Legionnaires' disease: a national
      approach.
AB  - BACKGROUND: To stop a possible outbreak of Legionnaires' disease (LD) at an early
      stage an outbreak detection programme was installed in The Netherlands. METHODS:
      The programme consisted of sampling and controlling of potential sources to which
      LD patients had been exposed during their incubation period. Potential sources
      were considered to be true sources of infection if two or more LD patients
      (cluster) had visited them, or if available patients' isolates and environmental
      Legionella spp. were indistinguishable by amplified fragment length polymorphism
      genotyping. RESULTS: Rapid sampling and genotyping as well as cluster recognition
      helped to target control measures. Despite these measures, two small outbreaks
      were only stopped after renewal of the water system. The combination of
      genotyping and cluster recognition lead to 29 of 190 (15%) patient-source
      associations. CONCLUSION: Systematic sampling and cluster recognition can
      contribute to outbreak detection and lead to cost-effective secondary prevention
      of Legionnaires' disease.

PMID- 16956793
TI  - Targeting mast cells in the treatment of functional gastrointestinal disorders.
AB  - Enhanced knowledge of the pathophysiological basis of functional gastrointestinal
      disorders indicates that low-grade mucosal inflammation and mast cell hyperplasia
      are common findings. Mast cells are multipotent and mucosa-dwelling residents are
      uniquely located to communicate with host immune and nervous supersystems and
      with the gut microflora to provide tight microenvironmental conditions.
      Maintenance of homeostasis within this integrated defense system is crucial for
      symbiotic health, whereas breakdown of that balance might lead to uncontrolled
      mucosal and systemic inflammation. Numerous advances have recently emerged in the
      understanding of regulatory mechanisms of mast cell activation, development and
      homing to mucosal surfaces, as well as of the role of mast cells in key steps of
      mucosal inflammation. Such observations have stimulated the development of
      candidate drugs, such as tryptase or Syk inhibitors, that might be useful for the
      treatment of gastrointestinal functional disorders.

PMID- 16956794
TI  - Tissue distribution of blood group membrane proteins beyond red cells: evidence
      from cDNA libraries.
AB  - The proteins of blood group systems are expressed on red blood cells (RBC) by
      definition. We searched nucleotide databases of human expressed sequence tags
      (EST) to collate the distribution of 22 distinct membrane proteins in cells and
      tissues other than RBC. The documented blood group genes are: MNS, Rh, Lutheran,
      Kell, Duffy, Kidd, Diego, Yt, Xg, Scianna, Dombrock, Colton, Landsteiner-Wiener,
      Kx, Gerbich, Cromer, Knops, Indian, Ok, Raph, John-Milton-Hagen and Gill. The
      genes were grouped according to their overall and their relative expression in
      embryo and adults. We describe the distribution of EST in cells, tissues and cell
      lines with a focus on non-RBC tissues.

PMID- 16956795
TI  - Cell-gene delivery of brain-derived neurotrophic factor to the mouse inner ear.
AB  - Sensorineural hearing loss is a common disability, but treatment options are
      currently limited to cochlear implants and hearing aids. Studies are therefore
      being conducted to provide alternative means of biological therapy, including
      gene therapy. Safe and effective methods of gene delivery to the cochlea need to
      be developed to facilitate the clinical application of these therapeutic
      treatments for hearing loss. In this study, we examined the potential of cell
      gene therapy with nonviral vectors for delivery of therapeutic molecules into the
      cochlea. NIH3T3 cells were transfected with the brain-derived neurotrophic factor
      (Bdnf) gene using lipofection and then transplanted into the mouse inner ear.
      Immunohistochemistry and Western blotting demonstrated the survival of grafted
      cells in the cochlea for up to 4 weeks after transplantation. No significant
      hearing loss was induced by the transplantation procedure. A Bdnf-specific enzyme
      linked immunosorbent assay revealed a significant increase in Bdnf production in
      the inner ear following transplantation of engineered cells. These findings
      indicate that cell-gene delivery with nonviral vectors may be applicable for the
      local, sustained delivery of therapeutic molecules into the cochlea.

PMID- 16956796
TI  - Gaps and forks in DNA replication: Rediscovering old models.
AB  - Most current models for replication past damaged lesions envisage that
      translesion synthesis occurs at the replication fork. However older models
      suggested that gaps were left opposite lesions to allow the replication fork to
      proceed, and these gaps were subsequently sealed behind the replication fork. Two
      recent articles lend support to the idea that bypass of the damage occurs behind
      the fork. In the first paper, electron micrographs of DNA replicated in UV
      irradiated yeast cells show regions of single-stranded DNA both at the
      replication forks and behind the fork, the latter being consistent with the
      presence of gaps in the daughter-strands opposite lesions. The second paper
      describes an in vitro DNA replication system reconstituted from purified
      bacterial proteins. Repriming of synthesis downstream from a blocked fork
      occurred not only on the lagging strand as expected, but also on the leading
      strand, demonstrating that contrary to widely accepted beliefs, leading strand
      synthesis does not need to be continuous.

PMID- 16956797
TI  - Carotid body chemosensory activity and ventilatory chemoreflexes in cats persist
      after combined cholinergic-purinergic block.
AB  - Acetylcholine (ACh) and ATP have been proposed as excitatory co-transmitters
      operating at synapses between glomus cells and sensory nerve endings of the
      carotid body (CB). To test such hypothesis, we performed experiments on cats
      under pentobarbitone anesthesia and breathing spontaneously. Cholinergic and
      purinergic agonists and antagonists were given into one common carotid artery.
      Chemoreflex ventilatory changes initiated from the ipsilateral CB or chemosensory
      activity from the ipsilateral carotid nerve were recorded. Agonists ACh,
      nicotine, epibatidine, ATP, betagamma-methylene-ATP and gammaS-ATP induced
      transient chemoreflex enhancements of ventilation or increased chemosensory
      activity. When given in combination, mecamylamine and suramin suppressed both
      nicotine- and ATP-induced ventilatory chemoreflexes or chemosensory responses.
      However, neither chemoreflex hyperventilation induced by brief hypoxic exposures
      or steady-state hypoxic levels, nor chemosensory excitation elicited by these
      maneuvers were eliminated. Asphyxia-induced chemosensory excitation was not
      reduced by combined blockade of ACh and ATP receptors. Furthermore, ventilatory
      or chemosensory depression evoked by 100% O2 tests was unmodified, thus
      evidencing that basal chemosensory drive in normoxia was not suppressed by
      combined cholinergic-purinergic blockade. Therefore, although ACh and ATP may
      participate in chemoexcitation of the CB, their involvement fails to explain the
      origin of chemosensory discharges from synaptic transmission between glomus cells
      and chemosensory nerve endings of the CB.

PMID- 16956798
TI  - Association and dissociation of the cell puncturing complex of bacteriophage T4
      is controlled by both pH and temperature.
AB  - The tail lysozyme, gp5, of bacteriophage T4 is a trimeric protein and all the
      subunits are nicked between Ser351 and Ala352 during assembly through processing.
      When subsequently heated, the resulting (gp5*)(3) (gp5C)(3) (the asterisk "*"
      denotes that the intact pre-gp5 trimer has been nicked) dissociates into three
      gp5* (three independent N-terminal monomeric peptides, that carry lysozyme
      moieties at the C-termini of gp5*), and a C-terminal trimeric beta-helical
      structure (gp5C)(3). The interaction between gp27 and gp5* during infection is
      sundered by reducing pH. This dissociation would be physiologically relevant
      because the lysozyme moieties should be free in the periplasm (where the pH is
      low) and would digest the peptidoglycan layer, thereby enabling the tail tube to
      contact the inner membrane, and probably help to form a pore for DNA injection.

PMID- 16956799
TI  - Novel composite fiber structures to provide drug/protein delivery for medical
      implants and tissue regeneration.
AB  - A novel class of bioresorbable composite (core/shell) fiber structures loaded
      with bioactive agents was developed and studied. These unique polymeric
      structures are designed to combine good mechanical properties with a desired
      controlled release profile, in order to serve as scaffolds for tissue
      regeneration applications and as basic elements of medical implants. These
      core/shell fiber structures were formed by "coating" core polymer fibers with
      drug/protein-containing poly(dl-lactic-co-glycolic acid) porous structures. The
      shell preparation ("coating") was performed by the freeze-drying of water-in-oil
      emulsions. Both water soluble and water insoluble agents can be incorporated in
      these structures and their activity is preserved, since the fiber fabrication
      requires neither high temperatures nor harsh solvents in the vicinity of the
      bioactive agents. Examples for release profiles of protein (horseradish
      peroxidase) and drug (paclitaxel) are presented. We have demonstrated that
      appropriate selection of the emulsion's parameters can yield a variety of new
      core/shell fiber structures with desirable drug/protein release behavior. This
      will lead to the engineering of new implants and scaffolds, and will advance the
      field of tissue regeneration and medical implants.

PMID- 16956800
TI  - Covalently crosslinked chitosan hydrogel: properties of in vitro degradation and
      chondrocyte encapsulation.
AB  - In vitro degradation and chondrocyte-encapsulation of chitosan hydrogel made of
      crosslinkable and water-soluble chitosan derivative (CML) at neutral pH and body
      temperature were studied with respect to weight loss, cytoviability, DNA content
      and cell morphology. In vitro degradation of the chitosan hydrogels was sensitive
      to their crosslinking degree and existence of lysozyme in the solution. Chitosan
      hydrogel (Gel-I5) fabricated from 1% CML and 5mM ammonium persulfate
      (APS)/N,N,N',N'-tetramethylethylenediamine (TMEDA) displayed no degradation in
      phosphate buffered saline (PBS) after 18d, but degraded completely at 8d in
      1mg/ml lysozyme/PBS. The chitosan hydrogel fabricated from 10mM APS/TMEDA was non
      degradable even in lysozyme/PBS solution after 18d. The hydrogel loaded with
      chondrocytes in cell culture medium, however, was susceptible to degradation
      during the in vitro culture. In vitro culture of the encapsulated chondrocytes in
      the chitosan hydrogel demonstrated that the cells retained round shaped
      morphology and could survive through a 12d-culture period, although the DNA assay
      detected an overall reduction of the cell number. These features provide a great
      opportunity to use the chitosan hydrogel as an injectable scaffold in tissue
      engineering and orthopaedics.

PMID- 16956802
TI  - Weight-bearing exercise and bone mineral accrual in children and adolescents: a
      review of controlled trials.
AB  - INTRODUCTION: Osteoporosis is a serious skeletal disease and as there is
      currently no cure, there is a large emphasis on its prevention, including the
      optimisation of peak bone mass. There is increasing evidence that regular weight
      bearing exercise is an effective strategy for enhancing bone status during
      growth. This systematic review evaluates randomised and non-randomised controlled
      trials to date, on the effects of exercise on bone mineral accrual in children
      and adolescents. METHODS: An online search of Medline and the Cochrane database
      enabled the identification of studies. Those that met the inclusion criteria were
      included in the review and graded according to risk for bias. RESULTS: Twenty-two
      trials were reviewed. Nine were conducted in prepubertal children (Tanner I), 8
      in early pubertal (Tanner II-III) and 5 in pubertal (Tanner IV-V). Sample sizes
      ranged from n=10 to 65 per group. Exercise interventions included games, dance,
      resistance training and jumping exercises, ranging in duration from 3 to 48
      months. Approximately half of the trials (n=10) included ground reaction force
      (GRF) data (2 to 9 times body weight). All trials in early pubertal children, 6
      in pre pubertal and 2 in pubertal children, reported positive effects of exercise
      on bone (P<0.05). Mean increases in bone parameters over 6 months were 0.9-4.9%
      in prepubertal, 1.1-5.5% in early pubertal and 0.3-1.9% in pubertal exercisers
      compared to controls (P<0.05). CONCLUSIONS: Although weight-bearing exercise
      appears to enhance bone mineral accrual in children, particularly during early
      puberty; it remains unclear as to what constitutes the optimal exercise
      programme. Many studies to date have a high risk for bias and only a few have a
      low risk. Major limitations concerned selection procedures, compliance rates and
      control of variables. More well designed and controlled investigations are
      needed. Furthermore, the specific exercise intervention that will provide the
      optimal stimulus for peak bone mineral accretion is unclear. Future quantitative,
      dose-response studies using larger sample sizes and interventions that vary in
      GRF and frequency may characterise the most and least effective exercise
      programmes for bone mineral accrual in this population. In addition, the
      measurement of bone quality parameters and volumetric BMD would provide a greater
      insight into the mechanisms implicated in the adaptation of bone to exercise.

PMID- 16956801
TI  - Influence of an LRP5 cytoplasmic SNP on Wnt signaling and osteoblastic
      differentiation.
AB  - The low density lipoprotein receptor-related protein 5 (LRP5) is a key
      determinant of bone mass, via the Wnt signaling pathway control of osteoblast
      function. This study examined human LRP5 signaling and the effects of an
      intracellular domain single nucleotide polymorphism (SNP: p.V1525A) on osteoblast
      differentiation and mineralization. Constitutively active LRP5 was constructed by
      deletion of the extracellular domain of LRP5 (LRP5DeltaN). Expression of
      LRP5DeltaN-V, which carries the allele p.1525V, induced higher beta-catenin/TCF
      LEF activity compared to LRP5DeltaN-A, which carries the allele p.1525A. In a
      yeast two-hybrid assay, LRP5DeltaN-V also demonstrated a stronger interaction
      with AXIN than LRP5DeltaN-A. Expression of either of the alleles did not change
      cell proliferation. However, cells expressing LRP5DeltaN-V showed increased
      alkaline phosphatase activity and bone nodule formation compared to cells
      transfected with empty vector or LRP5DeltaN-A after osteogenic supplement (OS:
      beta-glycerophosphate and l-ascorbic acid) treatment. Cells expressing LRP5DeltaN
      V revealed significantly increased bone sialoprotein (BSP) expression after 7
      days of OS treatment and maintained elevated expression until day 21. Osteocalcin
      (OCN) mRNA levels were increased after 14-21 days of OS treatment in LRP5DeltaN-V
      expressing cells. LRP5DeltaN-V expressing cells demonstrated positive interaction
      with BMP-2 signaling of transcription at the SBE-luc promoter. LRP5 signaling is
      affected by the cytoplasmic SNP, p.V1525A. mRNA levels of Runx2 and Osterix were
      not affected by this SNP.

PMID- 16956803
TI  - Zoledronic acid modulates function and differentiation of myeloid cells.

PMID- 16956804
TI  - Mesenchymal lineage potentials of AGM stromal clones.

PMID- 16956805
TI  - Inorganic polyphosphate induces apoptosis specifically in human plasma cells.

PMID- 16956806
TI  - Survival improvement in thalassemia: who should take the credit?

PMID- 16956807
TI  - Zoledronic acid for the treatment of thalassemia-induced osteonecrosis.

PMID- 16956808
TI  - The angiopoietin signaling pathway as a promising target for the treatment of
      acute myeloid leukemia.

PMID- 16956809
TI  - Searching for prognostic markers in childhood T-cell acute lymphoblastic
      leukemia.

PMID- 16956810
TI  - Redox revisited.

PMID- 16956811
TI  - Autologous transplantation in multiple myeloma.

PMID- 16956812
TI  - Thalassemia. A few new tiles in a large mosaic.

PMID- 16956813
TI  - Jean Bernard. Medicine, science, humanity.

PMID- 16956814
TI  - The effect of zoledronic acid on the function and differentiation of myeloid
      cells.
AB  - BACKGROUND AND OBJECTIVES: Bisphosphonates are widely used for treatment of
      osteoporosis and metastases of the skeletal system. Recent data suggest that
      bisphosphonates may not only reduce bone loss but also exert direct anti-tumor,
      anti-angiogenic and E inverted exclamation markE not T-cell activating effects,
      properties which depend at least partially on their affinity to phagocytosing and
      antigen-presenting cells (i.e. osteoclasts and monocytes). The latter represent
      the major source of dendritic cells (DC). Thus, we determined the
      immunomodulatory properties of zoledronic acid (ZA), a member of the latest
      generation of bisphosphonates. DESIGN AND METHODS: Primary human monocytes,
      macrophages, immature and mature dendritic cells were incubated with increasing
      doses of ZA for subsequent analysis of cell surface marker expression and
      cytokine production. In addition, phagocytic and allo-stimulatory properties,
      differentiation capacity, and NF-kB activation were determined. RESULTS:
      Therapeutic doses of ZA inhibited the in vitro generation of DC from monocytes,
      as shown by an impaired up-regulation of maturation markers. In parallel, ZA also
      impaired lipopolysaccharide-induced activation of NF-kB, which represents a
      critical factor for DC differentiation. Accordingly, the activation of allogeneic
      T cells by ZA-treated DC in a mixed-lymphocyte reaction was significantly
      reduced. Finally, ZA inhibited the production of tumor necrosis factor-a in
      monocyte-derived cells and impaired the phagocytic capacity of macrophages and
      immature DC. INTERPRETATION AND CONCLUSIONS: Therapeutic doses of ZA modulate
      monocyte, macrophage and DC function and might thereby modulate immune function.

PMID- 16956815
TI  - Mesenchymal lineage potentials of aorta-gonad-mesonephros stromal clones.
AB  - BACKGROUND AND OBJECTIVES: The characterization of stem cell microenvironments
      throughout ontogeny is of fundamental interest in the field of stem cell biology.
      Within the adult blood system, hematopoietic stem cells (HSC) are supported in
      the osteoblastic and endothelial bone marrow microenvironments. During mouse mid
      gestation, the first HSC emerge autonomously in the aorta-gonad-mesonephros (AGM)
      region. However, little is known about this microenvironment. To study the
      cellular complexity of the AGM hematopoietic microenvironment and its
      relationship to HSC, we examined the potential of AGM stromal clones to
      differentiate into several mesenchymal lineages. DESIGN AND METHODS: Stromal cell
      clones from the mid-gestation mouse were cultured in appropriate conditions known
      to support osteogenic, adipogenic, chondrogenic and endothelial differentiation.
      Potentials of the stromal cells were scored by morphological examination of the
      cultures, specific staining and gene expression profile. RESULTS: We show that
      most clones possess uni/bilineage osteogenic, adipogenic and/or endothelial
      potential. The differentiation potential of the stromal clones appears to relate
      to their site of origin but not to their ability to support hematopoiesis.
      Moreover, we show that AGM HSC activity is unaffected by the osteogenic
      differentiation of UG26.1B6 stromal cells. INTERPRETATION AND CONCLUSIONS: These
      results confirm the existence of mesenchymal stem/progenitor cells in the AGM
      region and suggest that the AGM hematopoietic microenvironment is highly complex,
      containing stromal cells with various mesenchymal lineage potentials.

PMID- 16956816
TI  - Inorganic polyphosphate and specific induction of apoptosis in human plasma
      cells.
AB  - BACKGROUND AND OBJECTIVES: Inorganic polyphosphate (polyP), a ubiquitous
      phosphate polymer with ATP-like bonds, has recently been related to a variety of
      functions including blood coagulation and cell proliferation. We investigated the
      effects of polyP in the biology of human plasma cells (PC), responsible for the
      production and maintenance of antibodies in response to antigens. DESIGN AND
      METHODS: The U266 myeloma cell line was used to study whether polyP affects
      immunoglobulin (Ig) secretion and survival. Different human cell lines were used
      to test the specificity of polyP on viability. We analyzed Ig secretion of PC
      from bone marrow and peripheral blood after polyP addition. A conventional
      tetanus toxoid booster immunization was used to increase the proportion of PC in
      order to examine the ex vivo effects of polyP. We also tested the effects of
      polyP on primary myeloma cells. Ig secretion and apoptosis were determined by
      ELISA and FACS respectively. RESULTS: Addition of polyP to human PC produced an
      unexpected inhibition of Ig secretion and stimulation of apoptosis. PolyP
      generated apoptosis specifically in PC, myeloma (malignant PC) cell lines,
      primary myeloma cells, and B lymphoid cell lines. Normal B cells, T cells, total
      blood mononuclear cells, and non-lymphoid cell lines were not affected by polyP.
      In the U266 myeloma cell line, polyP induced externalization of
      phosphatidylserine, activation of caspase-3, and arrest of the cell cycle. The
      protective effects of interleukin-6 did not overcome the polyP-induced apoptosis
      Interpretation and CONCLUSIONS: Taken together, our results suggest for the first
      time the relevance of the use of polyP to the humoral immune response and open
      prospects for polyP as a novel therapy for myeloma.

PMID- 16956817
TI  - Survival of medically treated thalassemia patients in Cyprus. Trends and risk
      factors over the period 1980-2004.
AB  - BACKGROUND AND OBJECTIVES: A large number of patients with thalassemia major have
      been born and treated exclusively in Cyprus. They have been managed according to
      standard international practice, but few have been transplanted. In 1999, a
      combination chelation regime with desferrioxamine and deferiprone was introduced.
      We analyzed survival trends in Cypriots and tried to identify factors associated
      with prolonged survival. DESIGN AND METHODS: We had incomplete information on
      births pre-1974 and complete information from 1974 onwards. Clinical data were
      incomplete pre-1980 and complete thereafter. We analyzed data on 539 patients
      born after 1960 and followed over the period 1980 to the end of 2004. RESULTS:
      There were 58 deaths, 31 (53.4%) of which where due to cardiac causes. In the
      complete birth cohort of 284 patients born after 1974, survival (95% CI) at 10,
      20 and 30 years was 100% (0); 98.5% (96.1-99.4) and 92.7% (86.7-96.1)
      respectively. There was a significant trend of increasing cardiac deaths between
      1980 and 2000 (p<0.001) and a decline after 2000 (p=0.06). In multivariate
      survival analysis, protective effects were found for female sex (hazard ratio,
      0.37, 95% CI 0.21-0.66; p<0.001), and post-2000 follow-up (hazard ratio, 0.44,
      95% CI 0.20-0.99; p<0.05), but not for genotype, treatment center or birth
      cohort. INTERPRETATION AND CONCLUSIONS: Most patients born after 1974 survive to
      at least the age of 30. There has been a marked improvement in survival for
      patients of all ages since 2000, which may be due to the introduction of
      combination chelation therapy.

PMID- 16956818
TI  - Zoledronic acid for the treatment of osteoporosis in patients with beta
      thalassemia: results from a single-center, randomized, placebo-controlled trial.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the effect of
      zoledronic acid (ZA) on thalassemia-induced osteoporosis. DESIGN AND METHODS: We
      studied 66 thalassemia patients with osteoporosis, who were randomized to receive
      4 mg ZA iv, every 6 months (23 patients; group A) or every 3 months (21 patients;
      group B), or to receive placebo every 3 months (22 patients; group C), for a
      period of 1 year. Bone mineral density (BMD) of the lumbar spine, femoral neck
      and wrist was determined before and 12 months after treatment. Pain scores and
      markers of bone resorption [C-telopeptide of collagen type-I (CTX), 5b-isoform of
      TRAP], bone formation [bone-alkaline phosphatase (bALP), osteocalcin (OC), C
      telopeptide of procollagen type-I (CICP)], and osteoclast stimulators [sRANKL,
      osteoprotegerin (OPG), osteopontin] were also measured at baseline and before
      each treatment administration. RESULTS: The values of CTX, bALP, CICP, sRANKL,
      and OPG were higher in the all patients than in the controls. Patients in group A
      showed no differences in BMD of all sites at 12 months, while they had reductions
      in bone pain, bALP, OC and OPG. Conversely patients in group B had a significant
      increase in their lumbar spine BMD, which was accompanied by dramatic reductions
      in bone pain, CTX, bALP, CICP, and OC. Patients in group C showed no alteration
      in BMD of any studied site or in bone pain, while they had an aggravation in bone
      resorption. INTERPRETATION AND CONCLUSIONS: ZA, at a dose of 4 mg, iv, every 3
      months is an effective treatment for increasing BMD and reducing bone resorption
      in thalassemia-induced osteoporosis.

PMID- 16956819
TI  - Expression of angiopoietins and their receptor Tie2 in the bone marrow of
      patients with acute myeloid leukemia.
AB  - BACKGROUND AND OBJECTIVES: Angiopoietin-1 (Ang-1) and its natural antagonist
      angiopoietin-2 (Ang-2), both ligands for the receptor tyrosine kinase Tie2, are
      known to play an essential role in normal and pathological angiogenesis. DESIGN
      AND METHODS: We investigated the expression of Ang-1, Ang-2 and Tie2 by
      immunohistochemical analyses in bone marrow biopsies of 64 adult patients with
      newly diagnosed acute myeloid leukemia (AML) and correlated angiogenic factor
      expression with clinicopathological variables and long-term survival. RESULTS:
      Expression of Ang-2 was significantly higher in the bone marrow of AML patients
      than in 16 control patients. In contrast, the levels of Ang-1 expression in AML
      patients did not differ from those found in controls. Thus, we observed a
      reversal of the Ang-1 and Ang-2 expression balance in the neoplastic bone marrow.
      Furthermore, Tie2 was significantly overexpressed in leukemic blasts. Patients
      expressing high levels of Ang-2 had significantly longer overall survival than
      those with low Ang-2 levels (52.7 vs. 14.7 months). Multivariate analysis
      revealed that karyotype and Ang-2 expression were independent prognostic factors
      for overall survival (hazard ratio [CI]: 3.06 [1.39-6.70] and 0.31 [0.14-0.69],
      respectively). INTERPRETATION AND CONCLUSIONS: These data provide evidence that
      the alteration of angiopoietin balance in favor of Ang-2 may play a critical role
      in the pathophysiology of AML. Furthermore, high pre-therapeutic levels of Ang-2
      in the bone marrow indicate a favorable prognosis in AML patients treated with
      polychemotherapy, although the mechanism is not yet known.

PMID- 16956820
TI  - The outcome of molecular-cytogenetic subgroups in pediatric T-cell acute
      lymphoblastic leukemia: a retrospective study of patients treated according to
      DCOG or COALL protocols.
AB  - BACKGROUND AND OBJECTIVES: Subgroups of T-cell acute lymphoblastic leukemia (T
      ALL), defined according to recurrent cytogenetic aberrations, may have different
      prognoses. The aim of this study was to determine the prognostic relevance of
      molecular-cytogenetic abnormalities in pediatric patients using quantitative real
      time polymerase chain reaction and fluorescence in situ hybridization. DESIGN AND
      METHODS: The patients were assigned to TAL1, HOX11/TLX1, HOX11L2/TLX3, or CALM
      AF10 subgroups. The cytogenetic subgroups were characterized in relation to
      immunophenotype and the expression of aberrantly expressed transcription factors.
      RESULTS: In our cohort study, CALM-AF10 was associated with an immature
      immunophenotype and poor outcome (p=0.005). HOX11L2 was associated with both
      immunophenotypically immature cases as well as cases committed to the gammadelta
      lineage. HOX11L2 was significantly associated with poor outcome (p=0.01),
      independently of the expression of CD1 or the presence of NOTCH1 mutations. TAL1
      abnormalities were associated with alphabeta-lineage commitment, and tended to be
      associated with a good outcome. Cells in HOX11 cases resembled early CD1-positive
      cortical thymocytes without expression of Cytbeta and TCR molecules. In relation
      to the expression of early T-cell transcription factors, high TAL1 levels were
      found in immunophenotypically-advanced cases, whereas high LYL1 levels were found
      in immature subgroups. INTERPRETATION AND CONCLUSIONS: The reported outcomes for
      HOX11L2-rearranged T-ALL cases are conflicting; the prognostic impact may depend
      on the therapy given. In our cohort, this cytogenetic aberration was associated
      with a poor outcome. Our data on CALM-AF10 rearranged T-ALL, albeit based on only
      three patients, suggest that this type of leukemia is associated with a poor
      outcome.

PMID- 16956821
TI  - Polymorphisms in the oxidative stress genes, superoxide dismutase, glutathione
      peroxidase and catalase and risk of non-Hodgkin's lymphoma.
AB  - BACKGROUND AND OBJECTIVES: The risk of non-Hodgkin's lymphoma (NHL) has been
      associated with inflammation. One possible mechanism may involve oxidative stress
      as reactive oxygen species (ROS) can generate pro-inflammatory signals. Anti
      oxidant enzymes including superoxide dismutase, glutathione peroxidase and
      catalase protect against the harmful effects of ROS. Genetic variation in the
      genes coding for these enzymes (SOD2, GPX1, and CAT, respectively) alters ROS
      production and therefore may provide a mechanism for the relationship between
      inflammation and NHL. DESIGN AND METHODS: Data from two population-based, case
      control studies of lymphoma in the UK (700 cases and 915 controls) and USA (1593
      cases and 2517 controls) were pooled to analyze polymorphisms in genes involved
      in the oxidative stress response (SOD2 Val16Ala, CAT C-262T and GPX1 Pro197Leu).
      RESULTS: No associations were observed between SOD2 Val16Ala and CAT C-262T and
      total NHL, diffuse large-B cell lymphoma or follicular lymphoma. However, when we
      looked at marginal zone lymphoma, a specific subtype of lymphoma characterised by
      inflammation, we found that homozygosity for the SOD2 16Ala allele was associated
      with a decreased risk among UK study participants. The GPX1 197Leu allele was
      weakly associated with NHL and follicular lymphoma. INTERPRETATION AND
      CONCLUSION: Analysis of genetic variation in oxidative stress genes in two
      lymphoma case-control studies suggests a possible role for oxidative stress in
      the risk of NHL. The risk modification is seen predominantly for marginal zone
      lymphomas which frequently arise in the context of chronic inflammation. However,
      in order to clarify the role of oxidative stress in the etiology of NHL analyses
      of additional polymorphisms and haplotypes in these and other genes involved in
      the oxidative stress response are needed.

PMID- 16956822
TI  - Intensive therapy for multiple myeloma in patients younger than 60 years. Long
      term results focusing on the effect of the degree of response on survival and
      relapse pattern after transplantation.
AB  - BACKGROUND AND OBJECTIVES: From 1994 to 1997 we conducted a population-based,
      prospective study on intensive therapy in newly diagnosed symptomatic myeloma
      patients younger than 60 years, comparing their survival to that of a
      conventionally treated historic population. Long-term results are presented,
      including the impact of the degree of response on survival and relapse pattern
      after transplantation. DESIGN AND METHODS: The prospective population was formed
      of 397 patients and the historic population of 313 patients. Both populations
      were calculated to comprise more than 75% of the expected number of new cases.
      RESULTS: After a median follow-up of 7 years survival was longer in the
      prospective population than in the historic one (median 60 versus 39 months;
      p=0.0002). When comparing only patients eligible for intensive therapy the median
      survival was 63 versus 44 months (p<0.0001). Attaining a complete response was
      associated with prolonged event-free survival but not overall survival. The
      pattern of relapse after transplantation was heterogeneous but could be divided
      into four major groups; insidious, classical, plasmacytoma form and transformed
      disease. The median survival after relapse was 29 months. The relapse pattern and
      time to relapse predicted outcome. Patients relapsing with an insidious or
      classical form of disease with skeletal events only, or after a long lasting
      first response were likely to respond well to conventional salvage therapy. In
      contrast, relapse with multiple symptoms, transformed disease or a short duration
      of first response implied bad prognosis. INTERPRETATION AND CONCLUSIONS: The
      relapse pattern after autologous transplantation is heterogeneous and response to
      salvage therapy is variable. The degree of response and event-free survival after
      transplantation are not reliable surrogate markers for survival.

PMID- 16956823
TI  - The phenotype of normal, reactive and malignant plasma cells. Identification of
      "many and multiple myelomas" and of new targets for myeloma therapy.
AB  - The aim of this review is to integrate non-exhaustive relevant data on the
      phenotype of human plasma cells (PC), including normal, reactive and malignant
      (multiple myeloma, MM) PC. This review focuses on (i) a universal marker of both
      normal and malignant plasma cells, CD138; (ii) markers related to malignancy
      i.e., CD19, CD27, CD28, and CD56; (iii) markers associated with signaling and
      severity of MM (CD45, CD221). Finally, this review presents data from normal PC
      up to human myeloma cell lines in order to: (i) define different entities of MM
      based on expression of CD19, CD20, CD27 and CD117; and (ii) identify new
      therapeutic targets.

PMID- 16956825
TI  - Two new mutations of the P5'N-1 gene found in Italian patients with hereditary
      hemolytic anemia: the molecular basis of the red cell enzyme disorder.
AB  - Inherited pyrimidine 5'-nucleotidase type-1 (P5'N-1) deficiency is the most
      frequent abnormality of red cell nucleotide metabolism causing non-spherocytic
      hemolytic anemia. We describe two novel mutations in two Italian patients
      affected by P5'N-1 deficiency. One mutation is a two base deletion that occurs at
      the splice site junction between intron 7 and exon 8 (c.396-397del AG); the
      second is an in-frame deletion of three adjacent bases (c.427-429del CAA),
      leading to deletion of glutamine 143. The kinetic properties of Q143del variant
      were not grossly altered, but the variant was very heat unstable even at
      physiological temperatures.

PMID- 16956824
TI  - A prospective randomized controlled trial on the safety and efficacy of
      alternating deferoxamine and deferiprone in the treatment of iron overload in
      patients with thalassemia.
AB  - We compared the safety and efficacy of alternating deferoxamine and deferiprone
      with that of deferoxamine monotherapy. Sixty transfusion-dependent thalassemia
      patients regularly treated with deferoxamine were randomized to continue
      deferoxamine alone or to receive an alternating therapy for one year. Both arms
      resulted in equivalent decreases of serum ferritin and liver iron concentration.
      There was no significant difference in the proportion of patients with adverse
      events in the two therapy groups although the nature of the adverse events
      differed according to the chelation regimen.

PMID- 16956826
TI  - Dual-color split signal fluorescence in situ hybridization assays for the
      detection of CALM/AF10 in t(10;11)(p13;q14-q21)-positive acute leukemia.
AB  - We developed dual-color split fluorescence in situ hybridization (FISH) assays to
      detect AF10 and/or CALM rearrangements. Among nine cases of acute leukemia with
      translocation breakpoints at 10p13 and 11q14-21, a CALM/AF10 rearrangement was
      found in seven and was confirmed by reverse transcriptase polymerase chain
      reaction (RT-PCR) in all. In 2/7 cases, FISH detected CALM/AF10 in extramedullary
      leukemic infiltrations in the mediastinum and breast. As expected, FISH was less
      sensitive than RT-PCR for disease monitoring of CALM-AF10 positive cases. This
      new FISH assay reliably discriminates between MLL/AF10 and CALM/AF10 genomic
      rearrangements, identifies variant and complex CALM/AF10 translocations and
      detects the CALM/AF10 rearrangement in extramedullary leukemic infiltrations.

PMID- 16956827
TI  - DAP-kinase hypermethylation in the bone marrow of patients with follicular
      lymphoma.
AB  - We studied whether DAP-kinase hypermethylation plays a role as a prognostic
      marker in patients with follicular lymphoma (FL). We found that DAP-kinase was
      frequently hypermethylated in bone marrow (BM) samples of 52 FL patients at
      diagnosis (71%) and identified patients with worse progression-free survival
      (p=0.06). In particular, patients with histologically proven BM infiltration and
      DAP-kinase hypermethylation had a poorer outcome (p=0.037). In a total of 170 BM
      samples obtained at diagnosis or during follow-up, DAP-kinase hypermethylation
      and the bcl2/IgH rearrangement gave concordant results in 67% of samples (48%
      both positive, 19% both negative). Both mrakers were independent predictors of
      the disease status (p<0.001).

PMID- 16956828
TI  - Familial hemophagocytic lymphohistiocytosis in an adult patient homozygous for
      A91V in the perforin gene, with tuberculosis infection.
AB  - Perforin gene (PRF1) mutations have been reported in 20-30% of patients with
      familial hemophagocytic lymphohistiocytosis (FHL), an autosomal recessive
      disorder of infancy and early childhood that impairs or abolishes lymphocyte
      cytotoxicity. We report the first case of FHL in an adult patient homozygous for
      A91V in PRF1 with tuberculosis. The monozygotic twin of the patient is healthy.
      A91V confers genetic susceptibility for the development of FHL, but is not enough
      to trigger the disease on its own. We discuss the role of the A91V change
      together with M. tuberculosis infection as synergistic factors in the late onset
      of FHL.

PMID- 16956829
TI  - Contribution of low density lipoprotein receptor-related protein genotypes to
      coagulation factor VIII levels in thrombotic women.
AB  - The contribution of low density lipoprotein (LDL) receptor-related protein (LRP)
      to variance of factor VIII (FVIII) levels in plasma was investigated in
      thrombotic women through analysis of frequent LRP genotypes. The G allele of the
      LRP -25C/G polymorphism, predicting increased LRP expression, was associated with
      15% and 18% mean reductions of FVIII activity and protein levels, respectively.
      The combination of -25C/G LRP polymorphism with FVIII D1241E and ABO
      polymorphisms produced a gradient of FVIII levels, thus supporting the notion
      that several factors, acting in FVIII biosynthesis, post-translational
      modification and removal from circulation, have additive effects on the variance
      of FVIII levels in plasma.

PMID- 16956830
TI  - Detection of heterozygous large deletions in the antithrombin gene using
      multiplex polymerase chain reaction and denatured high performance liquid
      chromatography.
AB  - The present study reports a method for the easy, rapid and cost effective
      detection of heterozygous large deletions. As a model gene all exons of the
      antithrombin gene were amplified in a one tube multiplex polymerase chain
      reaction (PCR) and the products separated according to their size by reverse
      phase ion-pair high performance liquid chromatography. A significant reduction in
      the height of a peak in the probandOs sample compared to in the control indicates
      the presence of a large deletion of the corresponding allele. Using this approach
      we identified heterozygous deletions in four patients: the deletions affected
      exons 1 and 2, exon 7 and the whole antithrombin gene.

PMID- 16956831
TI  - Effect on survival of the development of late-onset non-infectious pulmonary
      complications after stem cell transplantation.
AB  - We evaluated the incidence, risk factors, and clinical outcome of late-onset non
      infectious pulmonary complications (LONIPC) in 599 patients who underwent
      hematopoietic allogeneic stem cell transplantation (HSCT). The 2-year cumulative
      incidence of LONIPC was 10% among the 438 patients surviving more than 3 months
      after HSCT. Transplants from an unrelated donor and occurrence of extensive
      chronic graft-versus-host disease were the variables significantly associated
      with the development of LONIPC. The 5-year overall survival was significantly
      worse among patients with LONIPC than among those without (34% vs 65%, p=0.009).
      Causes of death were respiratory failure and infections. The relapse rate was
      similar in the two groups.

PMID- 16956832
TI  - The influence of lysophosphatidic acid on the immunophenotypic differentiation of
      human monocytes into dendritic cells.
AB  - Lysophosphatidic acid (LPA), a naturally occurring phospholipid, has been
      suggested to have an immunoregulatory role. We investigated the effect of LPA on
      differentiation of human monocytes into dendritic cells (DC). We found that LPA
      affects DC differentiation from monocytes by blocking the expression of CD1a
      molecules on their surface in a dose-dependent manner.

PMID- 16956833
TI  - Influence of Ggamma-158C --> and beta- (AT)x(T)y globin gene polymorphisms on HbF
      levels in Italian beta-thalassemia carriers and wild-type subjects.
AB  - Clinical manifestations of beta-thalassemia (beta-thal) intermedia phenotypes are
      influenced by the persistence of fetal hemoglobin (HbF) and by several
      polymorphisms located in the promoters of A- and beta-globin genes. The aim of
      this study was to evaluate the distribution of the -158Ggamma (C-->T)
      polymorphism and of the (AT)x(T)y configuration, as well as their eventual
      association with elevated levels of HbF in 188 beta-thal carriers and 229 wild
      type individuals of Italian descent. The -158GgammaT and the (AT)9(T)5alleles
      were found to be associated with increased levels of HbF in beta-thal carriers,
      but not in wild-type subjects.

PMID- 16956834
TI  - ET-1 and ecNOS gene polymorphisms andsusceptibility to acute chest syndrome and
      painful vaso-occlusive crises in children with sickle cell anemia.
AB  - The association of endothelin 1 (ET-1) and endothelial constitutive nitric oxide
      synthase (ecNOS) gene polymorphisms (G5665T and T8002C, VNTR and T-786C
      respectively) with the occurrence of acute chest syndrome and painful vaso
      occlusive crises was evaluated in homozygous SS children. This retrospective
      study reveals that ET-1 T8002 and ecNOS C-786 alleles are associated with,
      respectively, an increased and a decreased risk of acute chest syndrome.

PMID- 16956835
TI  - Molecular characterization of thalassemia intermedia in Indians.
AB  - Thalassemia intermedia shows considerable heterogeneity. The purpose of this
      study was to evaluate the prevalence and effect of common molecular determinants
      in thalassemia intermedia. In 73 cases of thalassemia intermedia, the possible
      molecular basis was co-existent a-deletions (n=16/50), homozygous XmnI
      polymorphism (n=17/50), both factors (n=3/50), and milder beta-alleles (n=9/50)
      in homozygous beta-thalassemia (total 50 cases). In heterozygous beta
      thalassemia, alphaalphaalphaanti-3.7 triplication was the predominant factor
      (14/23 cases).

PMID- 16956836
TI  - Limited effects on JAK2 mutational status after pegylated interferon alpha-2b
      therapy in polycythemia vera and essential thrombocythemia.
AB  - Twenty-five patients with myeloproliferative diseases were treated with pegylated
      interferon alpha-2b. Prior to therapy, 15/25 patients had a JAK2(V617F) mutation.
      Eight JAK2-positive patients were on therapy in hematological complete remission
      at 24 months. Five of eight patients demonstrated a 1.2-3.6 fold reduction in the
      percentage of JAK2(V617F) cells.

PMID- 16956837
TI  - A new D816 c-KIT gene mutation in refractory AML1-ETO leukemia.
AB  - One of the most common genetic events in acute myeloid leukemia (AML) is the
      t(8;21) (q22;q22) translocation, which contributes to leukemic transformation.
      However, different lines of evidence suggest that the AML1-ETO rearrangement is
      not sufficient to cause the full leukemic phenotype. Secondary genetic
      alterations such as mutations in receptor tyrosine kinases are thus required to
      induce overt AML. The incidence of c-KIT mutations in exon 17 was evaluated in 37
      Spanish patients with AML1-ETO+ leukemias. c-KIT mutations were present in only
      two cases (6.6%) and were shown to be associated with an adverse outcome. The
      frequency of c-KIT mutations described here is much lower than in other reports.

PMID- 16956838
TI  - Telehematology: a pilot experience of cytological diagnosis of acute myeloid
      leukemia via the Internet. A GOELAMS study.
AB  - Although modern communication technology is well developed, telehematology does
      not readily lend itself to practical laboratory use. Multicenter therapeutic
      protocols may offer preferential opportunities. The cytologists of the AML-2001
      protocol established an innovative organization to demonstrate the reliability of
      the diagnostic assessment of acute myeloid leukemia through a rapid and
      decentralized exchange of information via the internet and to define the
      conditions optimizing expert diagnosis. Telediagnosis appears to be a powerful
      tool for cytological review and other issues.

PMID- 16956839
TI  - MLL/GAS7 fusion in a pediatric case of t(11;17)(q23;p13)-positive precursor B
      cell acute lymphoblastic leukemia.
AB  - MLL/GAS7, resulting from t(11;17)(q23;p13), has been reported in one case of
      treatment-related acute myeloid leukemia (AML). We present a de novo case of
      t(11;17)-positive pediatric acute lymphoblastic leukemia. Fluorescent in situ
      hybridization and reverse transcriptase polymerase chain reaction analyses
      revealed an MLL/GAS7 chimera identical to the one previously described in AML.
      The molecular genetic features of MLL/GAS7 and the clinical impact of t(11;17)
      are discussed.

PMID- 16956840
TI  - Translocation t(9;14)(p13;q32) in cases of splenic marginal zone lymphoma.
AB  - Translocation t(9;14)(p13;q32) involving PAX5 and IGH genes was first described
      in lymphoplasmacytic lymphoma. New data suggest that this translocation is not
      restricted to a specific morphologic subtype but occurs in other B-cell
      lymphomas. We present three cases with a diagnosis of splenic marginal zone
      lymphoma and t(9;14) confirmed by fluorescent in situ hybridization.

PMID- 16956842
TI  - Morbidity associated with bone marrow aspiration and trephine biopsy - a review
      of UK data for 2004.
AB  - Adverse events following bone marrow biopsy are rare but poorly documented.
      Annual UK surveys are building up a data-base on the frequency and nature of such
      complications, which will provide the evidence on which recommendations can be
      based. The latest annual survey documented 15 adverse events, mainly hemorrhagic,
      among 20323 procedures.

PMID- 16956841
TI  - The effect of IgVH mutational status on the induction of apoptosis by rituximab
      in patients with heavily pretreated B-cell chronic lymphocytic leukemia: evidence
      from a clinical phase I/II trial.
AB  - We investigated tumor cell apoptosis in vivo in 14 heavily pretreated patients
      with B-cell chronic lymphocytic leukemia undergoing rituximab monotherapy.
      Apoptosis induction was more pronounced in patients with mutated IgVH genes than
      in those with unmutated IgVH genes, independently of the levels of expression of
      CD20, CD38, and ZAP-70 and of the presence of 17p deletion. Our results suggest
      an association between IgVH gene mutational status and rituximab-induced
      apoptosis.

PMID- 16956851
TI  - The Strength-Focused and Meaning-Oriented Approach to Resilience and
      Transformation (SMART): A body-mind-spirit approach to trauma management.
AB  - This article introduces the Strength-focused and Meaning- oriented Approach to
      Resilience and Transformation (SMART) as a model of crisis intervention, which
      aims at discovering inner strengths through meaning reconstruction. Limitations
      of conventional crisis management and current findings in post-traumatic growth
      research are discussed. Instead of adopting a pathological framework, the SMART
      approach holds a holistic view of health, employs facilitative strategies, and
      promotes dynamic coping. Intervention components include Eastern spiritual
      teachings, physical techniques such as yoga and meditation, and psycho-education
      that promotes meaning reconstruction. Efficacy of the SMART model is assessed
      with reference to two pilot studies conducted in Hong Kong at the time when the
      SARS pandemic caused widespread fear and anxiety in the community. Response to
      potential criticisms of the SMART model is attempted.

PMID- 16956852
TI  - Extended outpatient civil commitment and treatment utilization.
AB  - OBJECTIVE: This study considers four hypotheses regarding the impact of extended
      involuntary outpatient commitment orders on services utilization. METHOD: All
      Victorian Psychiatric Case Register (VPCR) patients who had extended (180+ day)
      outpatient commitment orders in the nine year study period and a matched
      treatment compliant comparison group with extended periods of outpatient care (N
      = 1182), both with at least two years of post-episode experience, were evaluated.
      Pre/post episode utilization was compared via paired t tests with individuals as
      their own controls. Logistic and OLS regression as well as repeated measures
      ANOVA via the GLM SPSS program and post hoc t tests were used to evaluate between
      group and across time differences. RESULTS: Extended episodes of care for both
      groups were associated with reduced use of hospitalization and increases in
      outpatient services. Extended orders did not promote voluntary participation in
      the post-period. Outpatient services during the extended episode for those on
      orders were raised to the level experienced by the treatment compliant comparison
      group and maintained at that level via subsequent renewal of orders throughout
      the patients' careers. OLS regression results indicate that approximately six
      community care service days were required for those on orders to achieve a one
      day reduction in hospital utilization following the extended episode. CONCLUSION:
      Outpatient commitment for those on extended orders in the Victorian context
      enables a level of community-based services provision, unexpected in the absence
      of this delivery system, which provides an alternative to hospitalization.

PMID- 16956853
TI  - From a social issue to policy: Social work's advocacy for the rights of donor
      conceived people to genetic origins information in the United Kingdom.
AB  - This paper outlines a 22 year campaign to introduce openness into the arena of
      donor conception in the UK. It identifies key aspects of the development of an
      advocacy based approach to such work and argues that social work values and
      principles can prove key to identifying structural inequalities which are not
      necessarily based in socio-economic disadvantage. Donor conceived people may find
      themselves in families which enjoy material privilege but whose exposure to a
      legislative framework and dominant professional cultures within the treatment
      centres encourages secrecy around genetic origins. Social workers' experience of
      adoption and family work leads them to recognise the danger of such secrets
      within families. Turning such social issues into policy changes requires vision,
      strategic long term advocacy and partnership with those directly affected.

PMID- 16956854
TI  - Caregiving stressors and psychological distress among veteran resident and
      immigrant family caregivers in Israel.
AB  - The study compared caregiving stressors and psychological distress between
      Israeli veteran resident and immigrant family caregivers. It examined whether
      psychosocial variables (appraisal of caregiving, mastery, social support and
      coping) mediate the differences in psychological distress between these two
      groups. A total of 213 veteran resident and 206 immigrant (from the former Soviet
      Union) caregivers of chronically ill elderly were recruited from health services.
      The comparisons between the two groups were examined separately for spouse and
      adult child caregivers. The immigrant spouse and adult child caregivers reported
      significantly higher levels of caregiving stressors than veteran resident
      caregivers, but psychological distress was significantly higher only among the
      immigrant adult child caregivers. In multivariate analyses, the difference in
      psychological distress disappeared when caregiving stressors and mediating
      psychosocial variables were included in the regression models. Different
      caregiving stressors and psychosocial variables were associated with
      psychological distress among the spouses and among the adult child caregivers.
      The findings suggest that the caregiving stressors and psychosocial variables
      explain differences in psychological health outcomes between veteran resident and
      immigrant caregivers. Social work interventions should address these factors
      among caregivers, take into account the relationship to the care recipient, be
      culturally adapted to the immigrant caregivers, and target immigrant adult child
      caregivers in particular.

PMID- 16956855
TI  - When disaster becomes commonplace reaction of children and adolescents to
      prolonged terrorist attacks in Israel.
AB  - The aim of this study was to examine, in conditions of prolonged terror, the
      possible influences of yet another terrorist attack as an additional traumatic
      event on children's reactions in the emotional, behavioral, and cognitive
      spheres, and to identify any mediating factors. The sample included 747 students
      in junior high schools in three Israeli cities. None of the participants was
      directly exposed to terrorist attacks, but they all lived with the possibility of
      daily terror. The research focused on fear as the most common and widespread
      reaction to terror and war. Short-term and long-term symptoms of fear were
      studied. It was found that an additional terrorist attack had no significant
      influence on children's emotional, cognitive, or behavioral spheres. Terror that
      has become habitual becomes negligible. Children learn to adjust to loss without
      experiencing grief.

PMID- 16956856
TI  - Social workers confront terrorist victims: The interventions and the
      difficulties.
AB  - The article deals with unremitting stress experienced by social workers dealing
      with terror victims. The article will describe the activity of social workers
      responsible for setting up a hospital information center. It will describe how
      they assist families searching for their loved ones and the process of
      identifying victims. The process in which the uncertainty is treated, the anxiety
      is contained, bad news are conveyed and concrete solutions are provided, will be
      elaborated on. Special emphasis will be placed on the multifaceted complimentary
      relationship between team members and between the provision of support, role
      exchange and the opportunity to share difficult experiences. The team is expert
      in identifying both personal and collective signs of distress. This is of
      particular significance and importance in connection with compassion fatigue,
      survival guilt, anxiety, depression and on- going burnout, regarding themselves
      and their colleagues. The article will propose organizational and clinical
      solutions, which could also be of service to other frameworks within the health
      system.

PMID- 16956857
TI  - Learning from each other: The social work role as an integrated part of the
      hospital disaster response.
AB  - Australian social workers in health care have become important members of
      hospital disaster response teams. The development of the role and its integration
      into the mainstream disaster response has progressed over the last two decades.
      Recent international events have given affirmation to the importance of this
      role. The development of national and state based Disaster Management Plans in
      Australia began in the mid 1970's. Recognition of the need for experienced,
      skilled workers to provide emotional support, practical assistance and grief and
      bereavement counselling has resulted in the inclusion of social workers in
      several key parts of the disaster management response including the specialised
      area of Disaster Victim Identification. Following the Bali Bombing in October
      2002, social workers worked with the Police Missing Persons Unit to provide
      support to families and facilitate the collection of ante mortem information. The
      process by which new services come about can be intricate and complex. In the
      field of health social work, the contribution of international programs such as
      the Mt Sinai Leadership Enhancement Program cannot be underestimated. As the
      Social Work Director of Westmead Hospital, one of the largest hospital social
      work departments in the country, participating in this program provided
      opportunities to share professional experience with international colleagues,
      many of whom are experts in their field. The social work role in disaster
      response has become internationally recognised and is an example of how
      collaboration and shared information and learning, can result in a profession
      working together to support key principles and values of practice for the benefit
      of those in need.

PMID- 16956858
TI  - Academic--practice partnerships in practice research: A cultural shift for health
      social workers.
AB  - Academic practice partnerships in practice research support health social workers
      in engaging in research that is embedded within their practice. This shift in
      culture enables social workers to join in a health service discourse that is
      increasingly data -driven and focused on effective practice and demonstrated
      quality of care for patients. The mentoring model is described as enabling
      practitioners to superimpose research skills onto existing practice skills. An
      academic practice research collaboration can reduce the distance between research
      and practice, contribute to a body of knowledge for health social work and
      promote health social workers as 'research focused practitioners'.

PMID- 16956859
TI  - Outcomes from the Mount Sinai Social Work Leadership Enhancement Program:
      Evaluation and extrapolation.
AB  - This article presents an overview of outcomes from the Mount Sinai Leadership
      Enhancement Program as identified by previous program participants from
      Melbourne, Australia. These are categorised into: (1) Personal/professional, (2)
      Intra-organisational, (3) Interorganisational, and (4) International outcomes.
      Two illustrative examples are provided of international outcomes demonstrating
      how the ongoing commitment of Professor Epstein has extended and embedded the
      principles of practice-based research in Melbourne, and how the over-riding
      principles of the program have been applied by participants in establishing
      collaborative relationships with colleagues in our neighbouring South-East Asian
      region.

PMID- 16956860
TI  - Skills, bravery, courage, and foolhardiness: Seventy-five years of social work in
      health care in Melbourne, Australia.
AB  - The lessons from the history of health social work in Melbourne, Victoria can be
      extrapolated to social work in other parts of Australia and internationally.
      Based on consultation with social workers, archival material and personal
      reflections this article traces 75 years of health social work in Melbourne and
      Victoria within the context of the prevailing social influences. The profession,
      which was started by local opinion leaders and public demand, is now well
      established. Initially Australians looked to Britain to guide the new profession,
      but by the latter part of the twentieth century they increasingly looked to the
      USA. Many challenges still face health social work. Sharing of knowledge and
      experience will strengthen social work locally and internationally.

PMID- 16956861
TI  - The international exchange program: In the first person.
AB  - This commentary presents personal reflections on the Social Work Leadership
      Enhancement Program in the Department of Social Work Services at the Mount Sinai
      Medical Center in New York. The value of the program, not only for the
      participants from other countries, but also the value of the exposure of social
      workers from other countries to the department staff is recognized. The
      international influence is unequalled. How if affects and nurtures global social
      work thinking, its impact on those taking part in the program, as well as the
      ever-expanding influence of the program on a growing network of social workers is
      noted.

PMID- 16956862
TI  - Psychiatry, testimony, and Shoah: Reconstructing the narratives of the muted.
AB  - A 1999 examination of approximately 5000 long-term psychiatric patients in Israel
      identified 725 as Holocaust (Shoah) survivors. Review of these cases has shown
      that these patients had not been treated as a unique group, and that their trauma
      related illnesses had been neglected in their decades long treatment. We
      discovered that many of these patients had never openly shared their severe
      persecution history. We postulated that many of them could have avoided lengthy
      if not life-long psychiatric hospitalization had they been able to openly share
      that history. Instead, those gruesome and traumatic experiences remained
      encapsulated, split-off, causing the survivor to lead a double-life. These
      patients may physically inhabit the world as psychogeriatric patients, though
      emotionally they may remain in adolescence or childhood due to early traumatic
      experiences. Some twenty-six patients at two institutions gave consent to be
      interviewed by a professional team and have their testimonies recorded on
      videotape. The aim of this study was to investigate the role of video testimony
      as a potential useful psychotherapeutic clinical intervention. By videotaping
      testimonies of these patients' experiences before, during, and after World War
      II, we had created highly condensed texts that could be interpreted on a
      multiplicity of levels going far beyond the mere narrative content of clinical
      medical history. Joint observation, reiteration, and discussion of these
      testimonies with staff members and the patients themselves has been not only an
      interesting experience, but also one of therapeutic value yet to be fully
      appreciated.

PMID- 16956863
TI  - Stay tuned and find out.

PMID- 16956864
TI  - Methadone induction doses: are our current practices safe?
AB  - PURPOSE: To review the literature on methadone deaths and propose evidence-based
      dosing guidelines. METHODS: A literature search was conducted on overdose deaths
      during the induction phase. Data on methadone deaths from the Ontario coroner's
      office, as well as prescribing guidelines from different countries and
      jurisdictions, were reviewed. The information was collectively considered and,
      using the best available evidence, translated into safe dosing guidelines for
      methadone induction. RESULTS: A literature review found high death rates during
      the methadone induction period. Data from the Ontario coroner's office revealed
      that of deaths that were felt to be attributable to methadone overdose, the
      majority occurred in those who had consumed diverted methadone: of those deaths
      within a registered program, the majority occurred during the initial dosing
      phase. Despite high death rates during induction onto methadone treatment, many
      jurisdictions do not have prescribing guidelines that take this evidence into
      account. CONCLUSIONS: Safer prescribing guidelines are needed to reduce deaths
      during induction onto methadone treatment. Recommendations are made for safe
      methadone induction doses.

PMID- 16956865
TI  - Adolescent and young adult heroin patients: drug use and success in methadone
      maintenance treatment.
AB  - This study examined the impact of methadone maintenance treatment on an inclusive
      group of adolescent and young adult opiate-dependent patients, ages 15-23,
      admitted over a 6-year period, during their first year in the program. Retention
      in treatment was the primary outcome variable, and at 12 months, 48% were still
      in treatment. The findings were: (a) a stepwise discriminant function analysis
      revealed that patients who consistently used heroin were at a greater risk of
      leaving treatment within the first 12 months; (b) the use of cocaine was an
      indicator of higher levels of heroin use in those who reached the one-year mark;
      (c) among patients who stayed in treatment for one year, there was a significant
      reduction in heroin use, a trend toward a reduction in cocaine use, and no
      significant impact on benzodiazepine use; and (d) the group that stayed in
      treatment was slightly younger than the group that left before the first year
      ended. There were no gender or ethnic differences between the two groups.
      Suggestions for interventions that might improve treatment outcome are presented.

PMID- 16956866
TI  - A chart review comparing paregoric to methadone in the treatment of neonatal
      opioid withdrawal.
AB  - Neonatal opioid withdrawal often requires treatment but there have been few
      recent studies of current pharmacological interventions to guide treatment. This
      retrospective chart review provides an exploratory examination of newborns
      treated with either methadone or paregoric for opioid withdrawal and outlines
      dosage ranges and intervals, side effects, and clinical outcomes of the two
      regimens. The outcome variables examined were time to resolution of withdrawal
      symptoms, rate of decrease in symptom severity, and length of hospital stay.
      There were no observed differences in outcome variables between the two treatment
      groups and side effect profiles were similar. Dosages, dosage intervals, and
      tapering regimens were consistent with American Academy of Pediatrics
      recommendations. Although the sample size is small and standardized regimens were
      not used, this study provides preliminary data about dosing levels and dosing
      intervals of these two pharmacologic treatment agents. Both groups of infants had
      favorable outcomes, although given the variation in treatment regimens it is
      difficult to draw an equation of equivalency. These results are applicable to the
      design of future studies of pharmacological interventions.

PMID- 16956867
TI  - Within treatment drinking and surreptitious drinking during brief substance abuse
      treatment.
AB  - This project examined the frequency of within treatment drinking and
      surreptitious drinking among patients who attended a brief substance abuse
      treatment program that mandated within treatment abstinence. We defined
      surreptitious drinking as within treatment drinking that is kept hidden from
      treatment staff. Data for this project came from the anonymous exit surveys of
      275 patients. Forty-eight patients (17.45%) indicated that they engaged in within
      treatment drinking at least once. Forty-one of those patients (87%) kept the
      drinking hidden from treatment staff. The most common reason for patients keeping
      their drinking hidden was a fear of discharge from treatment. Within treatment
      drinkers were compared to within treatment abstainers in the extent to which
      their treatment was coerced, the extent to which treatment was perceived as
      helpful, and their posttreatment intentions for substance use and follow-up care.
      Differences between these two groups, and their implications, are discussed.

PMID- 16956868
TI  - Complicated hypertension related to the abuse of ephedrine and caffeine
      alkaloids.
AB  - Ephedra containing products (ECPs), which most often contain additional sources
      of caffeine alkaloids, may be an under-recognized cause of hypertension. ECPs,
      especially when used in combination or at higher than recommended doses, can
      cause life-threatening cardiovascular and neurological complications. We present
      a case of hypertensive encephalopathy with new onset generalized tonic-clonic
      seizure secondary to concomitant use of two OTC supplements containing a mixture
      of ephedrine and caffeine alkaloids.

PMID- 16956869
TI  - Dual psychiatric diagnosis and substance abuse in pathological gamblers: a
      preliminary gender comparison study.
AB  - BACKGROUND: Pathological Gambling (PG) is a highly prevalent and disabling
      impulse control disorder. Recent studies have consistently shown that PG patients
      have responded well to treatment with SSRI's, mood stabilizers, and opioid
      antagonists. These findings have supported the observation that PG is strongly
      associated with both mood and anxiety disorders as well as substance abuse. The
      aim of the study is to evaluate the comorbid psychiatric diagnoses in our sample.
      METHODS: Thirty-six female, and forty-two male PG's were enrolled in our study. A
      comprehensive psychiatric diagnostic evaluation was performed on all patients,
      and patients were screened for symptoms of depression and anxiety using the
      Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, the Yale
      Brown Obsessive Compulsive Scale, and the Frost Multidimensional Perfectionism
      Scale. In addition, the patients completed self-report questionnaires about their
      demographic status and substance abuse. RESULTS: The majority of patients were
      married with full or part-time employment. The study results demonstrated that PG
      in males is correlated with substance and alcohol abuse. Diagnoses, which were
      prevalent among our cohort of female PG's included major depression, affective
      disorders, anxiety disorders, and eating disorders. CONCLUSION: In our sample of
      PGs, the men and women had different patterns of psychiatric comorbidity. The
      different patterns of psychiatric comorbidity seen in our male versus female PG's
      raises the question of whether the underlying etiopathology in PG may differ
      according to gender.

PMID- 16956870
TI  - Forgiveness and alcohol problems among people entering substance abuse treatment.
AB  - Forgiveness is argued to be highly relevant to problematic substance use, yet
      supportive empirical evidence is lacking. Findings are presented from a
      longitudinal study exploring the relationship between religiousness and
      spirituality (RS) variables and alcohol use disorders. We examined forgiveness of
      self (ForSelf), of others (ForOthers), and by God (ByGod), hypothesizing positive
      relationships with RS and negative relationships with alcohol use and
      consequences, at both baseline (N = 157) and six-month follow-up (N = 126).
      ForSelf scores were significantly lower than ForOthers and ByGod scores, and
      ForOthers scores increased modestly over time. ByGod was most consistently
      associated with other RS variables. ForSelf and ForOthers were associated with
      alcohol-related variables at both time points, and baseline ForSelf and ForOthers
      were associated with fewer drinking consequences at follow-up, but not after
      controlling for other pertinent variables. ForSelf may be most difficult to
      achieve and thus most important to recovery, thereby preventing full recovery and
      fostering relapses.

PMID- 16956871
TI  - Evaluation of a model for the treatment of combined mental illness and substance
      abuse: the Bellevue model for peer-led treatment in systems change.
AB  - The present study evaluated a model program at Bellevue Hospital Center
      incorporating a peer-led self-help (PLSH) approach which can be applied to bring
      about systems-level change in a variety of settings where persons with dual
      diagnosis are encountered. A total of 461 consecutive MICA inpatient admissions
      were evaluated to compare the PLSH unit with two standard psychiatric units. The
      PLSH program was associated with a higher rate of acceptance of aftercare
      referral (93% vs. 74%) and aftercare attendance (52% vs. 30%) among patients with
      no prior psychiatric hospitalizations (N = 111). In addition, the PLSH program
      appeared to benefit chronically impaired MICA patients (N = 350) or those with a
      history of prior psychiatric hospitalizations, as they were more likely to accept
      referral to aftercare treatment than were chronic patients discharged from the
      standard psychiatric units (96% vs. 81%). Such a program, when more widely
      applied, could yield decreased recidivism and considerably lower medical,
      psychiatric, and economic cost.

PMID- 16956872
TI  - Heroin and cocaine dependence and the risk of accidental non-fatal drug overdose.
AB  - The relation between illicit drug dependence and the likelihood of drug overdose
      is unclear. We recruited 1,066 habitual drug users for this analysis through
      street-based outreach in New York City. In this sample, 99.3% of respondents used
      heroin in the past year and 87.1% of respondents used cocaine; 819 (77.5%) heroin
      users and 735 (79.2%) cocaine users were severely dependent on either drug
      respectively. In multivariable models, among heroin users, persons who were
      severely heroin dependent were less likely (OR = 0.6; 95% CI = 0.4-0.9) to have
      overdosed on any drug in the past year; among cocaine users, those who were
      severely cocaine dependent were more likely (OR = 1.6; 95% CI = 1.0-2.6) to have
      overdosed in the past year. The relation between illicit drug dependence and risk
      of overdose may vary for different patterns of drug dependence. These
      observations suggest that overdose prevention interventions, perhaps even those
      specifically targeting opiate overdose, may be more efficiently directed at
      individuals exhibiting cocaine dependence.

PMID- 16956873
TI  - Prescribing naloxone to actively injecting heroin users: a program to reduce
      heroin overdose deaths.
AB  - Heroin overdose deaths have increased alarmingly in Chicago over the past decade.
      Naloxone, an opioid antagonist with no abuse potential, has been used to reverse
      opiate overdose in emergency medical settings for decades. We describe here a
      program to educate opiate users in the prevention of opiate overdose and its
      reversal with intramuscular naloxone. Participant education and naloxone
      prescription are accomplished within a large comprehensive harm reduction program
      network. Since institution of the program in January 2001, more than 3,500 10 ml
      (0.4 mg/ml) vials of naloxone have been prescribed and 319 reports of peer
      reversals received. The Medical Examiner of Cook County reported a steady
      increase in heroin overdose deaths since 1991, with a four-fold increase between
      1996 and 2000. This trend reversed in 2001, with a 20% decrease in 2001 and 10%
      decreases in 2002 and 2003.

PMID- 16956874
TI  - Less pain, more gain: buprenorphine-naloxone and patient retention in treatment.
AB  - Research indicates that persons addicted to opiates are likely to relapse
      following treatment or are at risk of terminating treatment early. The withdrawal
      experience may be one factor underlying early treatment discharge and several
      medications, including buprenorphine-naloxone, have been used to reduce
      withdrawal symptoms during detoxification. This retrospective study sought to
      determine whether patients who received buprenorphine-naloxone were retained in
      treatment longer than those who did not receive the medication. Data were
      collected on 170 patients admitted to the detoxification unit who either received
      (n = 85) or did not receive (n = 85) the medication. Differences in lengths of
      stay were found between the groups, thus warranting future research on the
      usefulness of buprenorphine-naloxone during detoxification and subsequent
      treatment. The importance of detoxification as an initial phase of treatment in
      relation to patient retention is discussed.

PMID- 16956875
TI  - Anabolic-androgenic steroid abuse by physicians.
AB  - Physicians are not immune to the rising popularity of anabolic-androgenic steroid
      (AAS) abuse. We present three cases of physician-patients who recently required
      inpatient substance abuse treatment stemming from the abuse of AAS or related
      compounds. These individuals shared a number of clinical and psychological
      features that led to or resulted from their abuse of ergogenic substances. Each
      incurred severe professional, legal, domestic and/or health consequences as a
      result of their abuse. The common features identified in these patients suggest
      the presence of an overriding "risk behavior syndrome" that may predispose
      susceptible individuals to AAS abuse. The reinforcing properties of AAS and the
      potential for dependence remains an active area of research. Effective treatment
      of these individuals requires recognition of the causative factors as well as the
      high likelihood of other substance abuse that must also be addressed. With proper
      support and monitoring, these individuals can resume productive professional
      careers.

PMID- 16956876
TI  - Chondroitin sulfate perlecan enhances collagen fibril formation. Implications for
      perlecan chondrodysplasias.
AB  - Inactivation of the perlecan gene leads to perinatal lethal chondrodysplasia. The
      similarity to the phenotypes of the Col2A1 knock-out and the disproportionate
      micromelia mutation suggests perlecan involvement in cartilage collagen matrix
      assembly. We now present a mechanism for the defect in collagen type II fibril
      assembly by perlecan-null chondrocytes. Cartilage perlecan is a heparin sulfate
      or a mixed heparan sulfate/chondroitin sulfate proteoglycan. The latter form
      binds collagen and accelerates fibril formation in vitro, with more defined
      fibril morphology and increased fibril diameters produced in the presence of
      perlecan. Interestingly, the enhancement of collagen fibril formation is
      independent on the core protein and is mimicked by chondroitin sulfate E but
      neither by chondroitin sulfate D nor dextran sulfate. Furthermore, perlecan
      chondroitin sulfate contains the 4,6-disulfated disaccharides typical for
      chondroitin sulfate E. Indeed, purified glycosaminoglycans from perlecan-enriched
      fractions of cartilage extracts contain elevated levels of 4,6-disulfated
      chondroitin sulfate disaccharides and enhance collagen fibril formation. The
      effect on collagen assembly is proportional to the content of the 4,6-disulfated
      disaccharide in the different cartilage extracts, with growth plate cartilage
      glycosaminoglycan being the most efficient enhancer. These findings demonstrate a
      role for perlecan chondroitin sulfate side chains in cartilage extracellular
      matrix assembly and provide an explanation for the perlecan-null
      chondrodysplasia.

PMID- 16956877
TI  - Insights into deglutathionylation reactions. Different intermediates in the
      glutaredoxin and protein disulfide isomerase catalyzed reactions are defined by
      the gamma-linkage present in glutathione.
AB  - Glutaredoxins are small proteins with a conserved active site (-CXX(C/S)-) and
      thioredoxin fold. These thiol disulfide oxidoreductases catalyze disulfide
      reductions, preferring GSH-mixed disulfides as substrates. We have developed a
      new real-time fluorescence-based method for measuring the deglutathionylation
      activity of glutaredoxins using a glutathionylated peptide as a substrate. Mass
      spectrometric analysis showed that the only intermediate in the reaction is the
      glutaredoxin-GSH mixed disulfide. This specificity was solely dependent on the
      unusual gamma-linkage present in glutathione. The deglutathionylation activity of
      both wild-type Escherichia coli glutaredoxin and the C14S mutant was
      competitively inhibited by oxidized glutathione, with K(i) values similar to the
      K(m) values for the glutathionylated peptide substrate, implying that
      glutaredoxin primarily recognizes the substrate via the glutathione moiety. In
      addition, wild-type glutaredoxin showed a sigmoidal dependence on GSH
      concentrations, the activity being significantly decreased at low GSH
      concentrations. Thus, under oxidative stress conditions, where the ratio of
      GSH/GSSG is decreased, the activity of glutaredoxin is dramatically reduced, and
      it will only have significant deglutathionylation activity once the oxidative
      stress has been removed. Different members of the protein disulfide isomerases
      (PDI) family showed lower activity levels when compared with glutaredoxins;
      however, their deglutathionylation activities were comparable with their oxidase
      activities. Furthermore, in contrast to the glutaredoxin-GSH mixed disulfide
      intermediate, the only intermediate in the PDI-catalyzed reaction was PDI peptide
      mixed disulfide.

PMID- 16956878
TI  - Characterization of gene rearrangements leading to activation of MDR-1.
AB  - Expression of the MDR-1/P-glycoprotein gene confers drug resistance both in vitro
      and in vivo. We previously reported that gene rearrangements resulting in a
      hybrid MDR-1 transcript represent a common mechanism for acquired activation of
      MDR-1/P-glycoprotein. We have identified hybrid MDR-1 transcripts in nine MDR-1
      overexpressing cell lines and two patients with relapsed ALL. We characterize
      these rearrangements as follows. 1) Non-MDR-1 sequences in the hybrid MDR-1
      transcripts are expressed in unselected cell lines, showing that these sequences
      are constitutively expressed. 2) The rearrangements occur randomly and involve
      partner genes (sequences) on chromosome 7 and on chromosomes other than 7.
      Breakpoints have been characterized in six cell lines. In one, the rearrangement
      occurred within intron 2 of MDR-1; in the other five, the rearrangement occurred
      24 to >96 kb 5' of the normal start of transcription of MDR-1. In one cell line,
      homologous recombination involving an Alu repeat was observed. However, in the
      remaining five cell lines, nonhomologous recombination was observed. 3) The
      rearrangements arise during drug selection. The acquired rearrangements are not
      detected in parental cells. 4) Five of the six active promoters that captured MDR
      1 controlled MDR-1 from a distance of 29 to more than 110 kb 5' to MDR-1.
      Transcription was initiated in an antegrade or retrograde direction. We conclude
      that drug selection with natural products targeting DNA or microtubules leads to
      DNA damage, nonhomologous recombination, and acquired drug resistance, wherein
      MDR-1 expression is driven by a random but constitutively active promoter.

PMID- 16956880
TI  - Proteolytic cleavage and nuclear translocation of fibrocystin is regulated by
      intracellular Ca2+ and activation of protein kinase C.
AB  - Fibrocystin, a type I membrane protein of unknown function, is the protein
      affected in the autosomal recessive form of polycystic kidney disease. Here we
      show that fibrocystin undergoes regulated proteolysis. Several proteolytic
      cleavages occur within the predicted ectodomain, whereas at least one cleavage
      occurs within the cytoplasmic portion. The latter generates a C-terminal
      intracellular fragment that harbors the nuclear localization signal
      KRKVSRLAVTGERTATPAPKIPRIT and translocates to the nucleus. Proteolytic cleavage
      of fibrocystin occurs constitutively in long term cultures of polarized inner
      medullary collecting duct cells (mIMCD-3). Activation of protein kinase C and
      release of intracellular Ca2+ are required for proteolysis under these
      conditions. In short term cultures of human embryonic kidney 293 cells (HEK-293),
      proteolytic cleavage of fibrocystin can be elicited by stimulation of
      intracellular Ca2+ release or activation of protein kinase C. These results
      identify a novel Ca2+-dependent pathway that signals from fibrocystin located in
      the cell membrane to the nucleus.

PMID- 16956879
TI  - A viable amino acid editing activity in the leucyl-tRNA synthetase CP1-splicing
      domain is not required in the yeast mitochondria.
AB  - Aminoacyl-tRNA synthetases are a family of enzymes that are responsible for
      translating the genetic code in the first step of protein synthesis. Some
      aminoacyl-tRNA synthetases have editing activities to clear their mistakes and
      enhance fidelity. Leucyl-tRNA synthetases have a hydrolytic active site that
      resides in a discrete amino acid editing domain called CP1. Mutational analysis
      within yeast mitochondrial leucyl-tRNA synthetase showed that the enzyme has
      maintained an editing active site that is competent for post-transfer editing of
      mischarged tRNA similar to other leucyl-tRNA synthetases. These mutations that
      altered or abolished leucyl-tRNA synthetase editing were introduced into
      complementation assays. Cell viability and mitochondrial function were largely
      unaffected in the presence of high levels of non-leucine amino acids. In
      contrast, these editing-defective mutations limited cell viability in Escherichia
      coli. It is possible that the yeast mitochondria have evolved to tolerate lower
      levels of fidelity in protein synthesis or have developed alternate mechanisms to
      enhance discrimination of leucine from non-cognate amino acids that can be
      misactivated by leucyl-tRNA synthetase.

PMID- 16956881
TI  - Selective blockade of glycoprotein VI clustering on collagen helices.
AB  - Platelet activation by collagen relies on the interaction of the receptor
      glycoprotein VI (GPVI) with collagen helices. We have previously generated two
      recombinant single chain human antibodies (scFvs) to human GPVI. The first,
      10B12, binds to the collagen-binding site on the apical surface between the two
      immunoglobulin-like domains (D1D2) of the receptor and so directly inhibits GPVI
      function. The second, 1C3, binds D1D2 independently of 10B12 and has been shown
      to have a more subtle effect on platelet responses to collagen. Here we have
      shown that 1C3 potentiates the effect of 10B12 on platelet aggregation induced by
      collagen and cross-linked collagen-related peptide (CRP-XL). We investigated this
      by measuring the effect of both scFvs on the binding of D1D2 to immobilized
      collagen and CRP. As expected, 10B12 completely inhibited binding of GPVI to each
      ligand in a dose-dependent manner. However, 1C3 inhibited only a proportion of
      GPVI binding to its ligands, implying that it interferes with another aspect of
      ligand recognition by GPVI. To further understand the mode of inhibition, we used
      a unique set of CRPs in which the content of critical glycine-proline
      hydroxyproline (GPO) triplets was varied in relation to an "inert" scaffold
      sequence of GPP motifs. We observed that a stepwise increase in D1D2 binding with
      (GPO)(2) content was blocked by 1C3. Together these results indicate that 1C3
      inhibits clustering of the immunoglobulin-like domains of GPVI on collagen/CRPs,
      a conclusion that is supported by mapping the 1C3 epitope to the region including
      isoleucine 148 in D2.

PMID- 16956882
TI  - Protein kinase A-mediated phosphorylation of connexin36 in mouse retina results
      in decreased gap junctional communication between AII amacrine cells.
AB  - Gap junctions in AII amacrine cells of mammalian retina participate in the
      coordination of the rod and cone signaling pathway involved in visual adaptation.
      Upon stimulation by light, released dopamine binds to D(1) receptors on AII
      amacrine cells leading to increased intracellular cAMP (cyclic adenosine
      monophosphate) levels. AII amacrine cells express the gap junctional protein
      connexin36 (Cx36). Phosphorylation of Cx36 has been hypothesized to regulate gap
      junctional activity of AII amacrine cells. However, until now in vivo
      phosphorylation of Cx36 has not been reported. Indeed, it had been concluded that
      Cx36 in bovine retina is not phosphorylated, but in vitro phosphorylation for
      Cx35, the bass ortholog of Cx36, had been shown. To clarify this experimental
      discrepancy, we examined protein kinase A (PKA)-induced phosphorylation of Cx36
      in mouse retina as a possible mechanism to modulate the extent of gap junctional
      coupling. The cytoplasmic domains of Cx36 and the total Cx36 protein were
      phosphorylated in vitro by PKA. Mass spectroscopy revealed that all four possible
      PKA consensus motifs were phosphorylated; however, domains point mutated at the
      sites in question showed a prevalent usage of Ser-110 and Ser-293. Additionally,
      we demonstrated that Cx36 was phosphorylated in cultured mouse retina.
      Furthermore, activation of PKA increased the level of phosphorylation of Cx36.
      cAMP-stimulated, PKA-mediated phosphorylation of Cx36 protein was accompanied by
      a decrease of tracer coupling between AII amacrine cells. Our results link
      increased phosphorylation of Cx36 to down-regulation of permeability through gap
      junction channels mediating light adaptation in the retina.

PMID- 16956883
TI  - The single transmembrane segment drives self-assembly of OutC and the formation
      of a functional type II secretion system in Erwinia chrysanthemi.
AB  - Many pathogenic Gram-negative bacteria secrete toxins and lytic enzymes via a
      multiprotein complex called the type II secretion system. This system, named Out
      in Erwinia chrysanthemi, consists of 14 proteins integrated or associated with
      the two bacterial membranes. OutC, a key player in this process, is probably
      implicated in the recognition of secreted proteins and signal transduction. OutC
      possesses a short cytoplasmic sequence, a single transmembrane segment (TMS), and
      a large periplasmic region carrying a putative PDZ domain. A hydrodynamic study
      revealed that OutC forms stable dimers of an elongated shape, whereas the PDZ
      domain adopts a globular shape. Bacterial two-hybrid, cross-linking, and pulldown
      assays revealed that the self-association of OutC is driven by the TMS, whereas
      the periplasmic region is dispensable for self-association. Site-directed
      mutagenesis of the TMS revealed that cooperative interactions between three polar
      residues located at the same helical face provide adequate stability for OutC
      self-assembly. An interhelical H-bonding mediated by Gln(29) appears to be the
      main driving force, and two Arg residues located at the TMS boundaries are
      essential for the stabilization of OutC oligomers. Stepwise mutagenesis of these
      residues gradually diminished OutC functionality and self-association ability.
      The triple OutC mutant R15V/Q29L/R36A became monomeric and nonfunctional. Self
      association and functionality of the triple mutant were partially restored by the
      introduction of a polar residue at an alternative position in the interhelical
      interface. Thus, the OutC TMS is more than just a membrane anchor; it drives the
      protein self-association that is essential for formation of a functional
      secretion system.

PMID- 16956884
TI  - Molecular mechanism of adaphostin-mediated G1 arrest in prostate cancer (PC-3)
      cells: signaling events mediated by hepatocyte growth factor receptor, c-Met, and
      p38 MAPK pathways.
AB  - Adaphostin (NSC680410), a small molecule congener of tyrphostin AG957, has been
      demonstrated previously to have significant anti-proliferative effects in several
      leukemia models. However, this effect of adaphostin in adherent cells/solid tumor
      models has not been examined. In this study, we investigated the anti
      proliferative effects of adaphostin in the human prostate cancer cell line PC-3.
      Specifically, we explored the potential molecular mechanism(s) by which
      adaphostin elicits its anti-proliferative effect(s). We demonstrate that
      adaphostin inhibits the proliferation of PC-3 cells by inducing a G(1) phase cell
      cycle arrest. This adaphostin-induced G(1) arrest was associated with an increase
      in the expression of p21 and p27 and a decrease in the expression of G(1)
      specific cyclins (cyclin A, D1, and D3) and cyclin-dependent kinases 4 and 6.
      Consequently, a dramatic decrease in the phosphorylation of retinoblastoma
      protein was also observed. Additionally, we found that adaphostin treatment
      induced a decrease in the phosphorylation of nucleophosmin, a major nuclear
      phosphoprotein, and that this decreased phosphorylation was a result of the p21-
      and p27-mediated inactivation of cyclin E-cyclin-dependent kinase 2 complex
      kinase activity. Furthermore, we have determined that the adaphostin-mediated
      cell cycle arrest of PC-3 cells is dependent upon activation of the p38 MAPK. We
      also demonstrate that the hepatocyte growth factor receptor-c-Met is involved in
      the adaphostin-mediated signaling events that regulate p38 MAPK. Taken together,
      these results identify for the first time a signaling cascade of adaphostin
      mediated G(1) phase-specific cell cycle arrest in PC-3 cells. These findings
      suggest that the tyrphostin member has a broader spectrum of activity than
      originally predicted.

PMID- 16956885
TI  - Plant seed peroxygenase is an original heme-oxygenase with an EF-hand calcium
      binding motif.
AB  - A growing body of evidence indicates that phytooxylipins play important roles in
      plant defense responses. However, many enzymes involved in the biosynthesis of
      these metabolites are still elusive. We have purified one of these enzymes, the
      peroxygenase (PXG), from oat microsomes and lipid droplets. It is an integral
      membrane protein requiring detergent for its solubilization. Proteinase K
      digestion showed that PXG is probably deeply buried in lipid droplets or
      microsomes with only about 2 kDa at the C-terminal region accessible to
      proteolytic digestion. Sequencing of the N terminus of the purified protein
      showed that PXG had no sequence similarity with either a peroxidase or a
      cytochrome P450 but, rather, with caleosins, i.e. calcium-binding proteins. In
      agreement with this finding, we demonstrated that recombinant thale cress and
      rice caleosins, expressed in yeast, catalyze hydroperoxide-dependent mono
      oxygenation reactions that are characteristic of PXG. Calcium was also found to
      be crucial for peroxygenase activity, whereas phosphorylation of the protein had
      no impact on catalysis. Site-directed mutagenesis studies revealed that PXG
      catalytic activity is dependent on two highly conserved histidines, the 9 GHz EPR
      spectrum being consistent with a high spin pentacoordinated ferric heme.

PMID- 16956886
TI  - Sulfonylureas correct trafficking defects of disease-causing ATP-sensitive
      potassium channels by binding to the channel complex.
AB  - ATP-sensitive potassium (K(ATP)) channels mediate glucose-induced insulin
      secretion by coupling metabolic signals to beta-cell membrane potential and the
      secretory machinery. Reduced K(ATP) channel expression caused by mutations in the
      channel proteins: sulfonylurea receptor 1 (SUR1) and Kir6.2, results in loss of
      channel function as seen in congenital hyperinsulinism. Previously, we reported
      that sulfonylureas, oral hypoglycemic drugs widely used to treat type II
      diabetes, correct the endoplasmic reticulum to the plasma membrane trafficking
      defect caused by two SUR1 mutations, A116P and V187D. In this study, we
      investigated the mechanism by which sulfonylureas rescue these mutants. We found
      that glinides, another class of SUR-binding hypoglycemic drugs, also markedly
      increased surface expression of the trafficking mutants. Attenuating or
      abolishing the ability of mutant SUR1 to bind sulfonylureas or glinides by the
      following mutations: Y230A, S1238Y, or both, accordingly diminished the rescuing
      effects of the drugs. Interestingly, rescue of the trafficking defects requires
      mutant SUR1 to be co-expressed with Kir6.2, suggesting that the channel complex,
      rather than SUR1 alone, is the drug target. Observations that sulfonylureas also
      reverse trafficking defects caused by neonatal diabetes-associated Kir6.2
      mutations in a way that is dependent on intact sulfonylurea binding sites in SUR1
      further support this notion. Our results provide insight into the mechanistic and
      structural basis on which sulfonylureas rescue K(ATP) channel surface expression
      defects caused by channel mutations.

PMID- 16956887
TI  - Procyclic Trypanosoma brucei expresses separate sialidase and trans-sialidase
      enzymes on its surface membrane.
AB  - The procyclic stage of Trypanosoma brucei in the insect vector expresses a
      surface-bound trans-sialidase (TbTS) that transfers sialic acid from
      glycoconjugates in the environment to glycosylphosphatidylinositol-anchored
      proteins on its surface membrane. RNA interference against TbTS abolished trans
      sialidase activity in procyclic cells but did not diminish sialidase activity,
      suggesting the presence of a separate sialidase enzyme for hydrolyzing sialic
      acid. A search of the T. brucei genome sequence revealed seven other putative
      genes encoding proteins with varying similarity to TbTS. RNA interference
      directed against one of these proteins, TbSA C, greatly decreased the sialidase
      activity but had no effect on trans-sialidase activity. The deduced amino acid
      sequence of TbSA C shares only 40% identity with TbTS but conserves most of the
      relevant residues required for catalysis. However, the sialidase has a tryptophan
      substitution for a tyrosine at position 170 that is crucial in binding the
      terminal galactose that accepts the transferred sialic acid. When this same
      tryptophan substitution in the sialidase was placed into the recombinant trans
      sialidase, the mutant enzyme lost almost all of its trans-sialidase activity and
      increased its sialidase activity, further confirming that the gene and protein
      identified correspond to the parasite sialidase. Thus, in contrast to all other
      trypanosomes analyzed to date that express either a trans-sialidase or a
      sialidase but not both, T. brucei expresses these two enzymatic activities in two
      separate proteins. These results suggest that African trypanosomes could regulate
      the amount of critical sialic acid residues on their surface by modulating
      differential expression of each of these enzymes.

PMID- 16956888
TI  - RNA editing by ADAR2 is metabolically regulated in pancreatic islets and beta
      cells.
AB  - RNA editing via the conversion of adenosine (A) to inosine (I) is catalyzed by
      two major families of adenosine deaminases acting on RNA (ADARs), ADAR1 and
      ADAR2. This genetic recoding process is known to play essential roles in the
      brain, due in part to changes in functional activities of edited neurotransmitter
      receptors and ion channels. Little is known, however, about the physiological
      regulation and function of A to I RNA editing in peripheral tissues and other
      biological processes. Here, we report that both ADAR1 and ADAR2 are expressed in
      the murine pancreatic islets, and ADAR2 is primarily localized in the islet
      endocrine cells. In contrast to ADAR1, ADAR2 transcripts in the pancreatic islets
      exhibit a nearly 2-fold increase in insulin-resistant mice chronically fed a high
      fat diet. Concurrent with this diet-induced metabolic stress, RNA editing in the
      islets is dramatically enhanced for the RNA transcripts encoding the ionotropic
      glutamate receptor subunit B. Moreover, ADAR2 protein expression is repressed in
      the islets under fuel deficiency condition during fasting, and this repression
      can be completely reversed by refeeding. We also show that, specifically in
      pancreatic beta-cell lines, not only the expression of ADAR2 but also the
      glutamate receptor subunit B editing and ADAR2 self-editing are markedly
      augmented in response to glucose at the physiological concentration for insulin
      secretion stimulation. Thus, RNA editing by ADAR2 in pancreatic islets and beta
      cells is metabolically regulated by nutritional and energy status, suggesting
      that A to I RNA editing is most likely involved in the modulation of pancreatic
      islet and beta-cell function.

PMID- 16956889
TI  - Aldose reductase mediates the lipopolysaccharide-induced release of inflammatory
      mediators in RAW264.7 murine macrophages.
AB  - Abnormal production of inflammatory cytokines and chemokines is a key feature of
      bacterial endotoxin, lipopolysaccharide (LPS)-induced inflammation, and
      cytotoxicity; however, the mechanisms regulating production of inflammatory
      markers remain unclear. Herein, we show that inhibition of the aldehyde
      metabolizing enzyme aldose reductase (AR; AKR1B3) modulates NF-kappaB-dependent
      activation of inflammatory cytokines and chemokines in mouse serum, liver, heart,
      and spleen. Pharmacological inhibition or small interfering RNA ablation of AR
      prevented the biosynthesis of tumor necrosis factor-alpha, interleukin 1beta,
      interleukin-6, macrophage-chemoattractant protein-1, and cyclooxygenase-2 and
      prostaglandin E(2) in LPS-activated RAW264.7 murine macrophages. The AR
      inhibition or ablation significantly attenuated LPS-induced activation of protein
      kinase C (PKC) and phospholipase C (PLC), nuclear translocation of NF-kappaB, and
      phosphorylation and proteolytic degradation of IkappaBalpha in macrophages.
      Furthermore, treatment of macrophages with 4-hydroxy-trans-2-nonenal (HNE), and
      cell-permeable esters of glutathionyl-4-hydroxynonanal (GS-HNE) and glutathionyl
      1,4-dihydroxynonane (GS-DHN) activated NF-kappaB and PLC/PKC. Pharmacological
      inhibition or antisense ablation of AR that catalyzes the reduction of GS-HNE to
      GS-DHN prevented PLC, PKC, IKKalpha/beta, and NF-kappaB activation caused by HNE
      and GS-HNE, but not by GS-DHN, suggesting that reduced GS-lipid aldehydes
      catalyzed by AR propagate LPS-induced production of inflammatory markers.
      Collectively, these data provide evidence that inhibition of AR may be a
      significant therapeutic approach in preventing bacterial endotoxin-induced sepsis
      and tissue damage.

PMID- 16956890
TI  - Functional cross-modulation between SOCS proteins can stimulate cytokine
      signaling.
AB  - SOCS (suppressors of cytokine signaling) proteins are negative regulators of
      cytokine signaling that function primarily at the receptor level. Remarkably, in
      vitro and in vivo observations revealed both inhibitory and stimulatory effects
      of SOCS2 on growth hormone signaling, suggesting an additional regulatory level.
      In this study, we examined the possibility of direct cross-modulation between
      SOCS proteins and found that SOCS2 could interfere with the inhibitory actions of
      other SOCS proteins in growth hormone, interferon, and leptin signaling. This
      SOCS2 effect was SOCS box-dependent, required recruitment of the elongin BC
      complex, and coincided with degradation of target SOCS proteins. Detailed
      mammalian protein-protein interaction trap (MAPPIT) analysis indicated that SOCS2
      can interact with all members of the SOCS family. SOCS2 may thus function as a
      molecular bridge between a ubiquitin-protein isopeptide ligase complex and SOCS
      proteins, targeting them for proteasomal turnover. We furthermore extended these
      observations to SOCS6 and SOCS7. Our findings point to a unique regulatory role
      for SOCS2, SOCS6, and SOCS7 within the SOCS family and provide an explanation for
      the unexpected phenotypes observed in SOCS2 and SOCS6 transgenic mice.

PMID- 16956891
TI  - Epstein-Barr virus induces cellular transcription factors to allow active
      expression of EBER genes by RNA polymerase III.
AB  - The EBER genes of Epstein-Barr virus (EBV) are transcribed by RNA polymerase
      (pol) III to produce untranslated RNAs that are implicated in oncogenesis. These
      EBER transcripts are the most highly expressed viral gene products in EBV
      transformed cells. We have identified changes to the cellular transcription
      machinery that may contribute to the high levels of EBER RNA. These include
      phosphorylation of ATF2, which interacts with EBER promoters. A second is
      induction of TFIIIC, a pol III-specific factor that activates EBER genes; all
      five subunits of TFIIIC are overexpressed in EBV-positive cells. In addition, EBV
      induces BDP1, a subunit of the pol III-specific factor TFIIIB. Although BDP1 is
      the only TFIIIB subunit induced by EBV, its induction is sufficient to stimulate
      EBER expression in vivo, implying a limiting function. The elevated levels of
      BDP1 and TFIIIC in EBV-positive cells stimulate production of tRNA, 7SL, and 5S
      rRNA. Abnormally high expression of these cellular pol III products may
      contribute to the ability of EBV to enhance growth potential.

PMID- 16956892
TI  - ApoO, a novel apolipoprotein, is an original glycoprotein up-regulated by
      diabetes in human heart.
AB  - Obesity is an independent risk factor for cardiac failure. Obesity promotes
      excessive deposition of fat in adipose and nonadipose tissues. Intramyocardial
      lipid overload is a relatively common finding in nonischemic heart failure,
      especially in obese and diabetic patients, and promotes lipoapoptosis that
      contributes to the alteration of cardiac function. Lipoprotein production has
      been proposed as a heart-protective mechanism through the unloading of surplus
      cellular lipids. We previously analyzed the heart transcriptome in a dog
      nutritional model of obesity, and we identified a new apolipoprotein, regulated
      by obesity in heart, which is the subject of this study. We detected this new
      protein in the following lipoproteins: high density lipoprotein, low density
      lipoprotein, and very low density lipoprotein. We designated it apolipoprotein O.
      Apolipoprotein O is a 198-amino acid protein that contains a 23-amino acidlong
      signal peptide. The apolipoprotein O gene is expressed in a set of human tissues.
      Confocal immunofluorescence microscopy colocalized apolipoprotein O and
      perilipins, a cellular marker of the lipid droplet. Chondroitinase ABC
      deglycosylation analysis or cell incubation with p-nitrophenyl-beta-d-xyloside
      indicated that apolipoprotein O belongs to the proteoglycan family. Naringenin or
      CP-346086 treatments indicated that apolipoprotein O secretion requires
      microsomal triglyceride transfer protein activity. Apolipoprotein O gene
      expression is up-regulated in the human diabetic heart. Apolipoprotein O promoted
      cholesterol efflux from macrophage cells. To our knowledge, apolipoprotein O is
      the first chondroitin sulfate chain containing apolipoprotein. Apolipoprotein O
      may be involved in myocardium-protective mechanisms against lipid accumulation,
      or it may have specific properties mediated by its unique glycosylation pattern.

PMID- 16956893
TI  - Elevated activity of STAT3C due to higher DNA binding affinity of phosphotyrosine
      dimer rather than covalent dimer formation.
AB  - Signal transducer and activator of transcription (STAT) proteins are involved in
      cell proliferation and survival, aspects of tissue differentiation and immune
      function. STAT3 appears to be fundamentally important for vertebrate organisms,
      being required for the self-renewal of embryonal stem cells in response to
      leukemia inhibitory factor signaling and for proliferation of some somatic cell
      types. Moreover, STAT3 is up-regulated in a range of tumors, and a modified
      version of STAT3 (STAT3C) has been shown to function as an oncogene, whereas
      inhibition of STAT3 can suppress tumor cell growth. The constitutive activity of
      oncogenic STAT3C was reported to depend on spontaneous dimerization directed by
      disulfide bonds in the absence of tyrosine phosphorylation. In fact, tyrosine
      phosphorylation consequent upon cytokine or mitogen-induced signaling events
      remains obligatory for STAT3C activation. Instead, the DNA-binding affinity of
      phospho-STAT3C is elevated resulting in a faster on-rate and slower off-rate. The
      faster on-rate sensitizes STAT3C to cytokine stimulation, and the slower off-rate
      protects it from inactivation by nuclear phosphatases. These changes account for
      the ability of STAT3C to up-regulate persistently the expression of STAT3 target
      genes and promote cell cycle progression.

PMID- 16956894
TI  - Experiences of belittlement and harassment and their correlates among medical
      students in the United States: longitudinal survey.
AB  - OBJECTIVE: To determine medical students' perceptions of having been harassed or
      belittled and their correlates, for the purposes of reducing such abuses. DESIGN:
      Longitudinal survey. SETTING: 16 nationally representative US medical schools.
      PARTICIPANTS: 2884 students from class of 2003. MAIN OUTCOME MEASURES:
      Experiences of harassment and belittlement at freshman orientation, at entry to
      wards, and in senior year by other students, by residents or fellows, by
      preclinical professors, by clinical professors or attendings, or by patients.
      RESULTS: 2316 students provided data (response rate 80.3%). Among seniors, 42%
      (581/1387) reported having experienced harassment and 84% (1166/1393)
      belittlement during medical school. These types of abuse were caused by other
      students (11% (158/1389) and 32% (443/1390) of students experienced such
      harassment or belittlement, respectively). Harassment and belittlement was also
      caused by residents (27% (374/1387) and 71% (993/1393)), preclinical professors
      (9% (131/1386) and 29% (398/1385)), clinical professors (21% (285/1386) and 63%
      (878/1390)), and patients (25% (352/1387) and 43% (592/1388)). Only 13%
      (181/1385) of students classified any of these experiences as severe. Medical
      students who reported having been harassed or belittled did not differ
      significantly from those not reporting such experiences by sex, ethnicity,
      political orientation, or religion. They did differ significantly by chosen
      specialty and were significantly more likely to be stressed, depressed, and
      suicidal, to drink alcohol or to binge drink, and to state that their faculty did
      not care about medical students. They were also significantly less likely to be
      glad they trained to become a doctor. CONCLUSION: Most medical students in the
      United States report having been harassed or belittled during their training.
      Although few students characterised the harassment or belittlement as severe,
      poor mental health and low career satisfaction were significantly correlated with
      these experiences.

PMID- 16956895
TI  - Beta2 adrenergic antagonist inhibits cerebral cortical oxygen delivery after
      severe haemodilution in rats.
AB  - BACKGROUND: Haemodilution has been associated with neurological morbidity in
      surgical patients. This study tests the hypothesis that inhibition of cerebral
      vasodilatation by systemic beta2 adrenergic blockade would impair cerebral oxygen
      delivery leading to tissue hypoxia in severely haemodiluted rats. METHODS: Under
      general anaesthesia, cerebral tissue probes were placed to measure temperature,
      regional cerebral blood flow (rCBF) and tissue oxygen tension (P(Br)O2) in the
      parietal cerebral cortex or hippocampus. Baseline measurements were established
      before and after systemic administration of either a beta2 antagonist (10 mg kg(
      1) i.v., ICI 118, 551) or saline vehicle. Acute haemodilution was then performed
      by simultaneously exchanging 50% of the estimated blood volume (30 ml kg(-1))
      with pentastarch. Arterial blood gases (ABGs), haemoglobin concentration (co
      oximetry), mean arterial blood pressure (MAP) and heart rate (HR) were also
      measured. Data were analysed using a two-way anova and post hoc Tukey's test
      [mean (sd)]. RESULTS: Haemodilution reduced the haemoglobin concentration
      comparably in all groups [71 (9) g litre(-1)]. There were no differences in ABGs,
      co-oximetry, HR and MAP measurements between control and beta2 blocked rats,
      either before or 60 min after drug or vehicle administration. In rats treated
      with the beta2 antagonist there was a significant reduction in parietal cerebral
      cortical temperature, regional blood flow and tissue oxygen tension, relative to
      control rats, 60 min after haemodilution (P<0.05 for each). These differences
      were not observed when probes were placed in the hippocampus. CONCLUSION:
      Systemic beta2 adrenergic blockade inhibited the compensatory increase in
      parietal cerebral cortical oxygen delivery after haemodilution thereby reducing
      cerebral cortical tissue oxygen tension.

PMID- 16956897
TI  - Perioperative management of antiplatelet agents in patients with coronary stents:
      recommendations of a French Task Force.

PMID- 16956898
TI  - Adverse events in anaesthetic practice.

PMID- 16956899
TI  - Unfractionated heparin and coronary artery stenting.

PMID- 16956900
TI  - Mid-calf position--an improved technique to place neuraxial anaesthesia.

PMID- 16956901
TI  - Safe placement of central venous catheters.

PMID- 16956902
TI  - The LOPSAQ study: 48 week analysis of a boosted double protease inhibitor regimen
      containing lopinavir/ritonavir plus saquinavir without additional antiretroviral
      therapy.
AB  - OBJECTIVES: To evaluate the virological, immunological and clinical responses to
      the boosted double protease inhibitor (PI) regimen combination of
      lopinavir/ritonavir and saquinavir ('LOPSAQ') without reverse transcriptase
      inhibitors (RTI) in HIV-positive patients who have few viable RTI treatment
      options. METHODS: Cohort study of 128 heavily pre-treated patients who were
      experiencing therapy failure on their current regimen due to RTI resistance
      and/or systemic toxicities. Patients with PI-resistance mutations or RTI toxicity
      underwent a structured treatment interruption (STI) (n=76) until virus reverted
      to wild-type or until resolution of toxicity symptoms. Baseline was defined as
      the time point when lopinavir/ritonavir plus saquinavir therapy was initiated.
      Virological response was defined as viral load<400 copies/mL at week 48. RESULTS:
      A total of 78 (61%) patients experienced a virological response to therapy (ITT).
      Median viral load at baseline was 5.06 log10 copies/mL; at week 48 median was
      2.16 log10 copies. Median CD4 at week 48 was 280 cells/mm3 compared with 172
      cells at baseline. At week 48, 78/128 patients were still on therapy. In
      univariable analyses, significant predictors of virological response included
      higher CD4 count (P<0.001), lower viral load (P=0.002), less PI-experience
      (P=0.006) at baseline and fewer PI-resistance mutations (P=0.043) at end of prior
      failing regimen; in the multivariable analysis only higher CD4 count at baseline
      (P=0.009) and fewer number of drugs previously taken (P=0.003) could be specified
      as independent predictors for response. CONCLUSIONS: The combination of
      lopinavir/ritonavir and saquinavir without RTIs is a potential option as salvage
      therapy for patients experiencing therapy failure due to RTI resistance or
      toxicity. This regimen may not be suitable for patients with very low baseline
      CD4 cell counts, very broad antiretroviral therapy experience or extensive PI
      resistance mutations.

PMID- 16956903
TI  - Penetration of moxifloxacin into the human pancreas following a single
      intravenous or oral dose.
AB  - OBJECTIVES: Failure to prevent secondary infectious complications in acute
      necrotizing pancreatitis (ANP) is attributable in part to the limited penetration
      of antimicrobial drugs. As newer quinolones are particularly attractive owing to
      their antimicrobial activity, for the first time we studied the penetration of
      moxifloxacin into pancreatic tissue in patients. PATIENTS AND METHODS: In this
      prospective, non-comparative clinical trial, 60 patients undergoing elective
      pancreas resection received a single oral or intravenous (iv) dose of 400 mg
      moxifloxacin for perioperative antimicrobial prophylaxis. The concentration of
      moxifloxacin was measured in samples taken from blood and from pancreatic tissue
      at the beginning and at the end of resection. RESULTS: Mean moxifloxacin
      concentrations in pancreatic tissue following iv or oral administration were
      3.1+/-0.9 and 2.7+/-1.4 mg/kg at 3-3.7 h post-dose (first sampling) and 3.6+/-1.5
      and 3.1+/-1.8 mg/kg at 4.3-5.3 h post-dose (second sampling), respectively.
      Corresponding mean plasma concentrations of moxifloxacin were 1.8+/-0.5 and 1.2+/
      0.6 mg/L (first sampling) and 1.5+/-0.4 and 1.0+/-0.5 mg/L (second sampling),
      respectively. From first to second sampling, the mean tissue-to-plasma ratios
      varied from 1.8+/-0.6 to 2.6+/-1.2 (iv) and from 2.4+/-0.8 to 3.1+/-1.2 (oral).
      Pancreatic tissue concentrations of moxifloxacin exceeded the MIC90 for the
      relevant pathogens covered by moxifloxacin for at least 5 h after dosing.
      CONCLUSIONS: Moxifloxacin has been demonstrated to penetrate efficiently into
      human pancreatic tissue following iv or oral administration. From a
      pharmacological perspective, moxifloxacin appears to be promising for prophylaxis
      and treatment of local pancreas infections. Whether it is beneficial in the
      prevention and therapy of infectious complications in patients with ANP should be
      investigated in a controlled clinical trial.

PMID- 16956904
TI  - Use of neuraminidase inhibitors to combat pandemic influenza.
AB  - Since the last influenza pandemic in 1968, neuraminidase (NA) inhibitors have
      been licensed for the treatment and prophylaxis of seasonal influenza. Continuing
      outbreaks of highly pathogenic avian influenza H5N1 since 2004 have focused
      attention on the timing of the next pandemic and preparedness plans. Although
      immunization is the principal means of influenza prophylaxis, a well-matched
      efficacious vaccine is unlikely to be widely available for several months
      following the emergence of the pandemic strain. NA inhibitors could be used to
      contain and eliminate an emerging pandemic virus at source. If unsuccessful, they
      could still play a crucial role in reducing the medical impact of pandemic
      influenza as it spreads through countries. Accordingly, many authorities are
      creating stockpiles of NA inhibitors. However, the use of stockpiled drugs for
      treatment or prophylaxis, the rapid delivery to newly diagnosed cases and unknown
      characteristics of an emergent pandemic strain pose significant challenges to
      determining optimal use of stockpiles.

PMID- 16956905
TI  - Efavirenz trough levels are not associated with virological failure throughout
      therapy with 800 mg daily and a rifampicin-containing antituberculosis regimen.
AB  - OBJECTIVES: To assess the safety and efficacy of efavirenz 800 mg daily in HIV
      infected patients with tuberculosis receiving a rifampicin-containing regimen and
      to analyse whether a relationship exists between efavirenz Cmin and its
      virological efficacy. METHODS: Prospective, open-labelled study including HIV
      infected patients on rifampicin and efavirenz 800 mg daily. Treatment adherence,
      adverse events (AEs), HIV-RNA levels, CD4 cell counts and efavirenz Cmin during
      and after finishing rifampicin treatment were evaluated. RESULTS: Eighty patients
      met the inclusion criteria. A permanent drug withdrawal due to AEs occurred in 10
      patients, 5 attributable to efavirenz, and 10 patients were lost to follow-up
      before the third month. Efavirenz Cmin levels with 800 mg plus rifampicin were
      similar to those with 600 mg after withdrawing rifampicin. Sixty patients were
      included in the efficacy analysis, eight experiencing virological failure. No
      relation was observed between the rate of virological failure and efavirenz Cmin,
      previous antiretroviral treatment or not, baseline CD4 counts or RNA-HIV. The
      only variable related to virological failure was irregular adherence [odds ratio,
      81 (95% CI: 5-1280); P=0.002]. CONCLUSIONS: Given the lack of a demonstrated
      relationship between efavirenz Cmin and its efficacy in our study, a firm
      recommendation cannot be made to always increase the dose to 800 mg/day when
      concomitantly given with rifampicin, but it seems a cautious approach to maintain
      the same efavirenz plasma levels as with 600 mg daily without rifampicin.
      Patients weighing<55 kg and also black, Asian and Hispanic subjects in whom
      genetic-based increased efavirenz plasma levels and rates of AEs have been
      observed may benefit from a dose of 600 mg.

PMID- 16956906
TI  - The usefulness of evaluative outcome measures in patients with multiple
      sclerosis.
AB  - To select the most useful evaluative outcome measures for early multiple
      sclerosis, we included 156 recently diagnosed patients in a 3-year follow-up
      study, and assessed them on 23 outcome measures in the domains of disease
      specific outcomes, physical functioning, mental health, social functioning and
      general health. A global rating scale (GRS) and the Expanded Disability Status
      Scale (EDSS) were used as external criteria to determine the minimally important
      change (MIC) for each outcome measure. Subsequently, we determined whether the
      outcome measures could detect their MIC reliably. From these, per domain the
      outcome measure that was found to be most sensitive to changes (responsive) was
      identified. At group level, 11 outcomes of the domains of physical functioning,
      mental health, social functioning and general health could reliably detect the
      MIC. Of these 11, the most responsive measures per domain were the Medical
      Outcome Study 36 Short Form sub-scale physical functioning (SF36pf), the
      Disability and Impact Profile (DIP) sub-scale psychological, the Rehabilitation
      Activities Profile sub-scale occupation (RAPocc) and the SF36 sub-scale health,
      respectively. Overall, the most responsive measures were the SF36pf and the
      RAPocc. In individual patients, none of the measures could reliably detect the
      MIC. In sum, in the early stages of multiple sclerosis the most useful evaluative
      outcome measures for research are the SF36pf (physical functioning) and the
      RAPocc (social functioning).

PMID- 16956907
TI  - EGFR and Src are involved in indole-3-carbinol-induced death and cell cycle
      arrest of human breast cancer cells.
AB  - Indole-3-carbinol (I3C), a dietary chemopreventive compound, induced marked
      reduction in epidermal growth factor receptor (EGFR) prior to cell death in cells
      representing three breast cancer subtypes. Signalling pathways, linking these
      events were investigated in detail. I3C modulated tyrosine phosphorylation from
      30 min in four cell lines. In MDA-MB-468 and HBL100 cells, it induced Src
      activation after 5 h. In MDA-MB-468 cells, I3C induced signalling between 4.5 and
      7 h, which involved sequential activation of Src, EGFR, STAT-1 and STAT-3,
      followed by EGFR degradation. It also induced physical association between
      activated Src and EGFR. In MCF7 and MDA-MB-231 cells, I3C modulated expression of
      cell cycle-related proteins, p21Cip1, p27Kip1, cyclin E, cyclin D1 and CDK6, with
      upregulation of p21Cip1 and cyclin E being dependent on Src. Inhibition of EGFR
      by specific inhibitors PD153035 or ZD1839 increased susceptibility to I3C-induced
      apoptosis of MCF7, MDA-MB-468 and MDA-MB-231 cells. Inhibition of Src sensitized
      MDA-MB-468 and MDA-MB-231 cells to I3C, whereas overexpression of c-Src increased
      resistance to I3C in MDA-MB-468 and HBL100 cells. Modulation of Src in MDA-MB-468
      cells influenced the basal level of EGFR expression and cell viability; the
      latter being positively correlated with EGFR activation levels. Therefore, EGFR
      and Src activities are essential for I3C-induced cell cycle arrest and death;
      however, I3C-induced pathways depend on specific features of breast cancer cells.
      The cancer types, which rely on 'EGFR addiction' or Src deregulation, are likely
      to be susceptible to I3C.

PMID- 16956908
TI  - The functional genetic variant Ile646Val located in the kinase binding domain of
      the A-kinase anchoring protein 10 is associated with familial breast cancer.
AB  - Overexpression of cAMP-dependent protein kinase A (PKA) is a hallmark of the
      great majority of human cancers including breast cancer. A-kinase anchoring
      proteins (AKAPs) coordinate the specificity of PKA signalling by localizing the
      kinase to its subcellular sites. We tested the hypothesis whether the functional
      amino acid exchange Ile646Val, located in the kinase-binding domain of AKAP10, is
      a low-penetrance familial breast cancer risk factor. Ile646Val alters the binding
      of AKAP10 to PKA and is associated with morbidity. The analysis of 787 BRCA1/2
      mutation-negative familial breast cancer patients and 993 controls revealed an
      association of the AKAP10 Ile646Val polymorphism with increased familial breast
      cancer risk [odds ratio (OR)=1.25, 95% confidence interval (CI) 1.03-1.51,
      P=0.024]. Our previous study has shown that AKAP13 Lys526Gln is associated with
      familial breast cancer (OR=1.58). Here, we discovered that carriers of both
      variants, AKAP10 Ile646Val and AKAP13 Lys526Gln, are at a further enhanced breast
      cancer risk (OR=2.41, 95% CI 1.30-4.46, P=0.005). PKA is a major target of
      therapeutic anticancer strategies. Phosphorylation of the estrogen receptor (ER)
      alpha by PKA induces resistance against the anti-estrogen tamoxifen. Our results
      indicate for the first time the importance of AKAP10 Ile646Val for familial
      breast cancer susceptibility. Due to the impact of Ile646Val on the subcellular
      localization of PKA, it will be interesting to investigate whether this
      polymorphism influences the effectiveness of PKA and tamoxifen based therapeutic
      anticancer concepts.

PMID- 16956909
TI  - Multi-factor dimensionality reduction applied to a large prospective
      investigation on gene-gene and gene-environment interactions.
AB  - It is becoming increasingly evident that single-locus effects cannot explain
      complex multifactorial human diseases like cancer. We applied the multi-factor
      dimensionality reduction (MDR) method to a large cohort study on gene-environment
      and gene-gene interactions. The study (case-control nested in the EPIC cohort)
      was established to investigate molecular changes and genetic susceptibility in
      relation to air pollution and environmental tobacco smoke (ETS) in non-smokers.
      We have analyzed 757 controls and 409 cases with bladder cancer (n=124), lung
      cancer (n=116) and myeloid leukemia (n=169). Thirty-six gene variants (DNA repair
      and metabolic genes) and three environmental exposure variables (measures of air
      pollution and ETS at home and at work) were analyzed. Interactions were assessed
      by prediction error percentage and cross-validation consistency (CVC) frequency.
      For lung cancer, the best model was given by a significant gene-environment
      association between the base excision repair (BER) XRCC1-Arg399Gln polymorphism,
      the double-strand break repair (DSBR) BRCA2-Asn372His polymorphism and the
      exposure variable 'distance from heavy traffic road', an indirect and robust
      indicator of air pollution (mean prediction error of 26%, P<0.001, mean CVC of
      6.60, P=0.02). For bladder cancer, we found a significant 4-loci association
      between the BER APE1-Asp148Glu polymorphism, the DSBR RAD52-3'-untranslated
      region (3'-UTR) polymorphism and the metabolic gene polymorphisms COMT-Val158Met
      and MTHFR-677C>T (mean prediction error of 22%, P<0.001, mean CVC consistency of
      7.40, P<0.037). For leukemia, a 3-loci model including RAD52-2259C>T, MnSOD
      Ala9Val and CYP1A1-Ile462Val had a minimum prediction error of 31% (P<0.001) and
      a maximum CVC of 4.40 (P=0.086). The MDR method seems promising, because it
      provides a limited number of statistically stable interactions; however, the
      biological interpretation remains to be understood.

PMID- 16956910
TI  - Expression of haematopoietic stem cell markers, CD133 and CD34 on human corneal
      keratocytes.
AB  - AIM: To study the expression of CD133 and CD34 antigens on cultured human
      keratocytes over time. METHODS: Primary cultures of human corneal stromal cells
      were established from explants derived from cadaver eye donors. The cultures were
      sorted for CD133+ and CD34+ cells using magnetic beads. Both the primary cultures
      and secondary passages of sorted cells were further analysed by flow cytometry
      and western blot analysis for expression of the same antigens over time. RESULTS:
      Four different cell populations-namely, CD133+, CD133-, CD34+ and CD34-, were
      identified in the culture samples. Two further specific subgroups were identified
      by flow cytometry: CD133+/CD34- cells and CD133+/CD34+ cells. Expression of CD133
      declines more than CD34 with time in cell cultures. Although most cells lost
      expression of these markers, small populations retained staining up to 5 weeks in
      culture. CONCLUSION: Human keratocytes express the haematopoietic stem cell
      markers CD133 and CD34. This expression decreases with time in culture, with most
      but not all cells losing expression. On the basis of these markers, the corneal
      stroma shows a heterogeneous population of cells. Expression or down regulation
      of expression of these molecules could represent different stages of activation
      of these cells.

PMID- 16956911
TI  - Tacrolimus immunosuppression in high-risk corneal grafts.
AB  - BACKGROUND: Unlike the immune privilege enjoyed by low-risk corneal grafts, high
      risk corneal grafts experience rejection rates comparable to liver and kidney
      transplants. Systemic immunosuppression reduces the risk of rejection in high
      risk corneal grafts. METHODS: Systemic tacrolimus, a specific T cell inhibitor,
      was used at a mean daily dose of 2.5 mg to immunosuppress 43 patients undergoing
      high-risk corneal transplantation. Immunosuppression was continued for a period
      of 18-24 months after the high-risk corneal graft. RESULTS: During a mean follow
      up period of 33.7 months, clarity of the graft was maintained in 65% of patients.
      Eight patients experienced rejection episodes while on tacrolimus, and this led
      to graft failure in five patients. CONCLUSION: Tacrolimus is relatively safe and
      effective in reducing rejection and prolonging graft survival in patients with
      high-risk keratoplasty compared with other series where similar immunosuppression
      was not used.

PMID- 16956912
TI  - Meta-analysis of randomised controlled trials comparing latanoprost with
      brimonidine in the treatment of open-angle glaucoma, ocular hypertension or
      normal-tension glaucoma.
AB  - AIM: To compare the efficacy and tolerability of latanoprost versus brimonidine
      in the treatment of open-angle glaucoma, ocular hypertension or normal-tension
      glaucoma. METHOD: Systematic review of randomised controlled trials comparing
      latanoprost and brimondine, identified by searches including Medline, Embase and
      Cochrane Controlled Trials Register. Two reviewers independently assessed trials
      for eligibility and quality and extracted data. Data were synthesised (random
      effects model) and expressed as the absolute mean intraocular pressure (IOP)
      reduction difference from baseline to end point for efficacy and relative risk
      for adverse events. Subgroup analysis and regression were used to explore
      heterogeneity according to patient characteristics, trial design and quality.
      RESULTS: 15 publications reporting on 14 trials (1784 participants) were included
      for meta-analysis. IOP reduction favoured latanoprost (weighted mean difference
      (WMD) = 1.10 mm Hg (95% confidence interval (CI) 0.57 to 1.63)). Significant
      heterogeneity was present (chi(2)(13) = 38.29, p = 0.001, I(2) = 66.0%). Subgroup
      analysis showed greater WMD for studies where data were analysed from end points
      >6 months duration, cross-over design, open-angle glaucoma or ocular hypertension
      and monotherapy. Multiple regression showed no significant association of WMD
      with trial duration (t(9) = 1.92, p = 0.09), trial design (t(9) = 1.79, p =
      0.11), trial quality (t(9) = -0.46, p = 0.66), or monotherapy or adjunctive
      therapy (t(9) = -2.14, p = 0.06). Fatigue was less commonly associated with
      latanoprost (RR = 0.27, 95% CI 0.08 to 0.88). Publication bias was not evident on
      visual inspection of a funnel plot. CONCLUSION: Latanoprost is more effective
      than brimonidine as monotherapy in lowering IOP. Brimonidine is associated with a
      higher rate of fatigue.

PMID- 16956914
TI  - Obstructive sleep apnoea inhibits the recovery of left ventricular function in
      patients with acute myocardial infarction.
AB  - AIMS: It has been suggested that obstructive sleep apnoea syndrome (OSA) may be a
      direct cause of left ventricular (LV) systolic dysfunction. This study was
      designed to examine our hypothesis that OSA inhibits the recovery of LV function
      in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: Our 86
      consecutive first-AMI patients underwent primary percutaneous coronary
      intervention (PCI). All patients underwent polysomnography and OSA was defined as
      an apnoea-hypoapnoea index (AHI) > or =15 events/h, of which more than 50% were
      obstructive. Left ventriculograms immediately after PCI and at 21 days were used
      to evaluate LV ejection fraction (LVEF), LV end-diastolic volume index, and
      regional wall motion (RWM) within the infarct area. OSA was observed in 37
      patients (43%). All three indices of LV function after primary PCI were
      comparable between the two groups. Increases in LVEF and RWM during admission
      were significantly lower in OSA patients than those without OSA (delta LVEF: 
      0.3+/-9.6 vs. 7.4+/-7.2%, P < 0.001; delta RWM: 0.26+/-1.04 SD/chord vs. 1.16+/
      1.20 SD/chord, P = 0.002). Multiple regression analysis showed that AHI
      correlated negatively with delta LVEF and delta RWM. CONCLUSION: The novel
      finding is that OSA may inhibit the recovery of LV function in patients with AMI.

PMID- 16956913
TI  - Fundus autofluorescence in exudative age-related macular degeneration.
AB  - AIM: To evaluate the distribution of fundus autofluorescence in patients with age
      related macular degeneration and choroidal neovascularisation (CNV). METHODS:
      Colour fundus photographs, fundus fluorescein angiograms (FFA) and fundus
      autofluorescence images were obtained from a group of 40 patients (43 eyes) with
      age-related macular degeneration and purely classic or occult CNV. Only patients
      with newly diagnosed CNV and in whom autofluorescence images were obtained within
      2 weeks from FFA were included. The distribution of autofluorescence was
      qualitatively evaluated, and the findings compared with those from colour fundus
      photographs and FFA. RESULTS: 29 (67%) eyes had classic CNV and 14 (33%) had
      occult CNV. In 26 (90%) eyes with classic CNV, a low autofluorescence signal was
      detected at the site of the CNV; in 7 (50%) eyes with occult CNV, multiple foci
      of low autofluorescence signal were detected. Outside the area affected by the
      lesion, homogeneous autofluorescence was observed in most of the cases (n = 33,
      77%). Similarly, homogeneous autofluorescence was commonly observed in fellow
      eyes (62%). A pattern of focal increased autofluorescence was rarely seen in eyes
      with CNV (n = 4, 9%) or in fellow eyes (n = 4, 15%). In 11 of 43 (25%) eyes,
      areas of increased autofluorescence, other than a pattern of focal increased
      autofluorescence, were detected. In four patients, autofluorescence images had
      been obtained before the development of CNV; in none was any increased
      autofluorescence detected before the formation of CNV. CONCLUSIONS: Distinct
      patterns of autofluorescence were observed in eyes with pure classic and occult
      CNV. Increased autofluorescence was rarely seen in eyes with CNV and in fellow
      eyes, suggesting that increased autofluorescence, and thus, retinal pigment
      epithelium lipofuscin, may not play an essential part in the formation of CNV.

PMID- 16956915
TI  - Huge right coronary artery aneurysm in a young adult.

PMID- 16956916
TI  - Atrial fibrillatory rate and sinus rhythm maintenance in patients undergoing
      cardioversion of persistent atrial fibrillation.
AB  - AIMS: The study set out to explore whether an index of atrial electrical
      electrophysiology can be used to predict atrial fibrillation (AF) relapse, and if
      the predictive properties differ as a result of arrhythmia duration. METHODS AND
      RESULTS: The study comprised 175 consecutive patients with persistent AF (median
      duration 94 days, range 2 to 1044) referred for cardioversion. Twenty-nine
      patients had arrhythmia duration under 30 days (median 5 days, range 2-26).
      Atrial fibrillatory rate (AFR) was estimated using a frequency power spectrum
      analysis of QRST-cancelled ECG. At 1-month follow-up, 56% of the patients had
      relapsed to AF. The pre-cardioversion mean AFR of those patients was 399+/-52
      fibrillations per minute (fpm) compared with 363+/-63 fpm among patients
      maintaining SR (P<0.0001). In patients with short AF duration, the difference was
      even more pronounced (424+/-52 vs. 345+/-65 fpm, P<0.01). In this group, a
      finding of an AFR above the mean value of the study population predicted AF
      relapse with high accuracy. CONCLUSION: In patients undergoing cardioversion of
      persistent AF, AF relapse is predicted by a higher AFR. A stronger association is
      seen in patients with short arrhythmia duration, reflecting either rapid
      remodelling or pre-existing changes in those who relapse to AF.

PMID- 16956917
TI  - A randomised study of peginterferon and ribavirin for 16 versus 24 weeks in
      patients with genotype 2 chronic hepatitis C.
AB  - BACKGROUND: The recommended treatment for patients infected with hepatitis C
      virus genotype 2 (HCV2) is pegylated interferon (peginterferon) and ribavirin for
      24 weeks. AIM: To assess whether a shorter 16-week treatment is as effective as a
      standard 24-week treatment. METHODS: Patients with HCV2 infection were randomised
      in a 1:2 ratio to either 16 weeks (n = 50) or 24 weeks (n = 100) of treatment
      with peginterferon alpha-2a (180 mug/week) and weight-based ribavirin 1000-1200
      mg/day, with a 24-week follow-up period. A rapid virological response (RVR) was
      defined as seronegative for HCV RNA at 4 weeks of treatment, and the primary end
      point, sustained virological response (SVR), as seronegative for HCV RNA at the
      24-week follow-up. RESULTS: The rate of RVR and SVR was 86% (43/50, 95%
      confidence interval (CI) 76% to 96%) and 94% (47/50, CI 87% to 100%),
      respectively, in the 16-week group, which was comparable to 87% (87/100, CI 80%
      to 94%) and 95% (95/100, CI 91% to 99%) in the 24-week group. Patients with RVR
      had a significantly higher SVR rate than patients without RVR in both 16-week
      (100% vs 57%, p = 0.015) and 24-week groups (98% vs 77%, p = 0.002). Multivariate
      analysis showed that RVR and age were independent factors associated with SVR.
      Both treatment arms were equally well tolerated. The incidence of alopecia was
      significantly higher in the 24-week group (49%) than in the 16-week group (20%, p
      = 0.001). CONCLUSION: 16 weeks and 24 weeks of peginterferon treatment with
      weight-based ribavirin at a dose of 1000-1200 mg/day provided equal efficacy in
      patients with HCV2 who achieved RVR at 4 weeks.

PMID- 16956918
TI  - Metabolic and cardiovascular risk profiles and hepatitis C virus infection in
      rural Egypt.
AB  - BACKGROUND AND AIMS: To investigate the relationship between lipid profiles and
      diabetes with past and chronic hepatitis C virus (HCV) infection among village
      residents of Egypt. PATIENTS AND METHODS: Fasting lipids and glucose profiles
      were compared among adults never infected with HCV (negative HCV antibodies),
      infected in the past (positive HCV antibodies and negative HCV RNA) and
      chronically infected (positive HCV antibodies and HCV RNA). RESULTS: Of the 765
      participants, 456 (59.6%) were female, and median age was 40 (range 25-88) years.
      Chronic HCV infection was present in 113 (14.8%) and past infection in 67 (8.8%).
      After adjustment for age and sex, participants with chronic HCV infection had
      lower plasma low density lipoproteins (LDL) cholesterol and triglyceride levels
      compared with those never infected (age and sex adjusted differences (95% CI)
      were -19.0 (-26.3 to -11.7) mg/dl and -26.2 (-39.0 to -13.3) mg/dl,
      respectively). In contrast, participants with cleared HCV infection had higher
      triglyceride levels compared with those never infected (age and sex adjusted
      difference (95% CI) was +16.0 (0.03 to 31.9) mg/dl). In multivariate analysis,
      participants with chronic HCV infection were more likely to have diabetes (OR
      3.05, 95% CI 1.19 to 7.81) compared with those never infected, independent of LDL
      cholesterol levels. CONCLUSION: In conclusion, this community based study has
      shown that in a single population, chronic HCV infection is associated with
      glucose intolerance and, despite that, a favourable lipid pattern. An intriguing
      finding was the high triglyceride levels observed among participants with past
      infection, suggesting that elevated triglycerides at the time of acute infection
      may facilitate viral clearance.

PMID- 16956919
TI  - Apoptosis of T cells and the control of inflammatory bowel disease: therapeutic
      implications.

PMID- 16956920
TI  - Targeted and regulable expression of transgenes in hepatic stellate cells and
      myofibroblasts in culture and in vivo using an adenoviral Cre/loxP system to
      antagonise hepatic fibrosis.
AB  - BACKGROUND: Activated hepatic stellate cells (HSCs) are an attractive target for
      antifibrotic therapy based on their key role in extracellular matrix accumulation
      during liver injury. AIM: : To develop a system for regulable and cell-specific
      gene expression in HSCs to enable targeted delivery of therapeutic genes. METHOD:
      Two types of recombinant adenoviral vectors were constructed, one expressing the
      Cre gene under the surveillance of specific promoters and the other containing a
      potent expression unit that was activated by Cre recombinase-mediated
      recombination to remove an upstream lox-flanked "stuffer" sequence, thereby
      amplifying the expression of downstream transgene of interest while maintaining
      specificity. RESULTS: When the promoter of the collagen 1A2 gene drove Cre
      recombinase expression in primary quiescent rat HSC, modest green fluorescence
      protein (GFP) expression was observed. However, in activated HSC, the collagen
      promoter effectively drove Cre recombinase activity, as assessed by the increased
      expression of GFP. In contrast, GFP expression was barely observed when the
      collagen promoter was expressed in hepatocytes. HSC-specific expression of Smad7
      considerably reduced the expression of type I collagen in culture and decreased
      fibrosis in two liver fibrosis models. Finally, to achieve targeted clearance of
      activated HSC in culture and in vivo, thymidine kinase was selectively expressed
      under the control of the collagen promoter, which conferred cell-specific killing
      by ganciclovir leading to reduced fibrosis. CONCLUSION: Our results show the
      potential utility of transcriptionally controlled gene therapy using a Cre/loxP
      system to ameliorate hepatic fibrosis in vivo.

PMID- 16956922
TI  - Renal amyloidosis in intravenous drug users.
AB  - BACKGROUND: Intravenous drug abuse is associated with a wide variety of acute and
      chronic medical complications. The increased longevity of drug users has seen the
      emergence of new diseases as a result of chronic bacterial and viral infection.
      We recently observed an increase in the number of cases of renal amyloidosis
      among intravenous drug users in central London. AIM: To describe here the
      demographic and clinical characteristics of such patients. METHODS: Patients were
      identified retrospectively from computerized patient renal biopsy records at
      University College London and Royal Free Hospitals from 1990-2005. Clinical
      information was collected from patient hospital records. RESULTS: We identified
      20 cases of AA amyloidosis; 65% occurred between January 2000 and September 2005.
      All were proteinuric (mean 7.3 g/l, range 0.5-14.8 g/l) and 13 required dialysis
      within 1 month of diagnosis. Of the remaining seven, four developed end-stage
      renal failure after mean follow-up of 16 months (range 6-30). Nine died, with
      median survival of 19 months (range 1-62); all deaths were due to sepsis.
      DISCUSSION: Secondary AA amyloidosis is a serious complication of chronic soft
      tissue infection in intravenous drug users in central London. Affected
      individuals invariably presented with nephrotic range proteinuria and advanced
      renal failure. Treatment options are limited and the outcome for such patients on
      renal replacement was poor. Cross-disciplinary strategies are needed to prevent
      this serious complication of long-term intravenous drug abuse.

PMID- 16956921
TI  - Mesenteric fat in Crohn's disease: a pathogenetic hallmark or an innocent
      bystander?

PMID- 16956923
TI  - Idiopathic pulmonary fibrosis: an update.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic lung condition of uncertain
      aetiology that should be considered in the differential diagnosis of patients who
      experience breathlessness, cough and reduced exercise tolerance. IPF is
      characterized histologically by the presence of usual interstitial pneumonia, and
      often has typical radiological appearances. Long-term successful management
      options are limited and frequently unsuccessful; as the disease progresses,
      palliation of symptoms becomes the mainstay of treatment. In a minority of
      patients, lung transplantation provides the only hope of long-term survival. The
      median survival of patients with IPF is approximately 3 years, which in turn
      emphasizes the need for further investigation into its pathogenesis and potential
      disease-modifying pharmacological therapies.

PMID- 16956924
TI  - Evaluating broad-spectrum antimicrobials.

PMID- 16956925
TI  - Heart failure: be aware of reversible causes.

PMID- 16956926
TI  - Prognostic serological markers of Henoch-Schonlein nephritis.

PMID- 16956927
TI  - Experiences and views of specialist registrars in geriatric medicine on 'do not
      attempt resuscitation' decisions: a sea of uncertainty?
AB  - BACKGROUND: Recent cultural changes place doctors under increasing pressure to
      work with their patients to reach decisions about end-of-life care. AIM: To
      survey the experience, practice and opinions of specialist registrars (SPRs) in
      geriatric medicine regarding 'do not attempt resuscitation' (DNAR) decisions.
      DESIGN: Postal questionnaire survey. METHODS: A questionnaire was mailed to all
      members registered as trainees (n = 408) with the British Geriatrics Society in
      November 2003; a reminder was sent nine weeks later. Responses were analysed
      using both quantitative and qualitative (thematic) approaches. RESULTS: Response
      rate was 62% (251/408), of whom 235 were still SpRs. Respondents played a major
      role in DNAR decision-making in their day-to-day clinical practice. Over a third
      of respondents did not feel that locally available guidelines were helpful. More
      than half sometimes disagreed with their consultants' decision, and a fifth were
      concerned about the possibility of complaints regarding the decisions they made.
      The majority felt uncomfortable discussing the issue with the patient, and were
      more likely to discuss the issue with relatives than with patients. DISCUSSION:
      Further support and training may improve confidence and positive experiences in
      relation to DNAR decision-making among training-grade doctors in the UK.

PMID- 16956928
TI  - Computer technology and the childhood immunization programme: an investigation of
      low uptake rates in Coventry Primary Care Trust.
AB  - BACKGROUND: The childhood vaccination programme in Coventry Primary Care Trust
      (PCT) has resulted in consistently low uptake rates for a number of years. After
      an evaluation of operational processes, an examination of the data systems was
      performed. METHODS: The under-reporting of vaccinations performed and methodology
      issues were investigated using data collected by the Child Health Information
      Department (CHID) and the Finance Department. RESULTS: Data held by the Finance
      Department result in an uptake rate of between 0.79 and 1.92% higher than those
      held by the CHID. Locally, the Southwest Child Health (SWIFT) system, the
      programme used to calculate uptake rates by many of the PCTs across the country,
      excludes those children residing outside the boundary but registered within it.
      Coventry PCT's Cover of Vaccination Evaluated Rapidly (COVER) statistics are
      based on a subgroup of the responsible population. CONCLUSIONS: The computer
      technology currently utilized by the NHS provides inaccurate statistics for the
      COVER programme. Systematic under-reporting to the CHID results in moderately
      lowered uptake rates. A programming anomaly in the SWIFT system has resulted in
      the collection of data based on a subgroup of the responsible population. This
      undermines the validity of the statistics collected and renders comparability of
      data between different PCTs, particularly those using different systems,
      difficult.

PMID- 16956929
TI  - Ferredoxin limits cyclic electron flow around PSI (CEF-PSI) in higher plants-
      stimulation of CEF-PSI enhances non-photochemical quenching of Chl fluorescence
      in transplastomic tobacco.
AB  - We tested the hypothesis that ferredoxin (Fd) limits the activity of cyclic
      electron flow around PSI (CEF-PSI) in vivo and that the relief of this limitation
      promotes the non-photochemical quenching (NPQ) of Chl fluorescence. In
      transplastomic tobacco (Nicotiana tabacum cv Xanthi) expressing Fd from
      Arabidopsis (Arabidopsis thaliana) in its chloroplasts, the minimum yield (F(o))
      of Chl fluorescence was higher than in the wild type. F(o) was suppressed to the
      wild-type level upon illumination with far-red light, implying that the transfer
      of electrons by Fd-quinone oxidoreductase (FQR) from the chloroplast stroma to
      plastoquinone was enhanced in transplastomic plants. The activity of CEF-PSI
      became higher in transplastomic than in wild-type plants under conditions
      limiting photosynthetic linear electron flow. Similarly, the NPQ of Chl
      fluorescence was enhanced in transplastomic plants. On the other hand, pool sizes
      of the pigments of the xanthophyll cycle and the amounts of PsbS protein were the
      same in all plants. All these results supported the hypothesis strongly. We
      conclude that breeding plants with an NPQ of Chl fluorescence increased by an
      enhancement of CEF-PSI activity might lead to improved tolerance for abiotic
      stresses, particularly under conditions of low light use efficiency.

PMID- 16956930
TI  - Task uncertainty and rationality in medical problem solving.
AB  - QUALITY ISSUE: Medical problem-solving situations are characterized by various
      degrees of 'task uncertainty'--i.e. uncertainty related to the definition of a
      problem, the effect of a technology, the value of a solution, and so on. The need
      for professional discretion varies and depends on the degree of perceived task
      uncertainty. SUGGESTED SOLUTION: In this report it is argued that, in order to
      obtain rationality in problem-solving processes, differences in the degree of
      task uncertainty need to be met by variation in the structure of the health care
      organization. IMPLICATIONS: The main implications of this view are that (under
      norms of rationality) problem-solving processes with low task uncertainty must be
      organized in one way and processes with high task uncertainty in another.
      Furthermore, processes with high and low task uncertainty also need to be
      evaluated according to different standards. Some hypotheses regarding the
      different organizational requirements are presented.

PMID- 16956931
TI  - Culture, language, and patient safety: Making the link.
AB  - It has been well recognized internationally that hospitals are not as safe as
      they should be. In order to redress this situation, health care services around
      the world have turned their attention to strategically implementing robust
      patient safety and quality care programmes to identify circumstances that put
      patients at risk of harm and then acting to prevent or control those risks.
      Despite the progress that has been made in improving hospital safety in recent
      years, there is emerging evidence that patients of minority cultural and language
      backgrounds are disproportionately at risk of experiencing preventable adverse
      events while in hospital compared with mainstream patient groups. One reason for
      this is that patient safety programmes have tended to underestimate and
      understate the critical relationship that exists between culture, language, and
      the safety and quality of care of patients from minority racial, ethno-cultural,
      and language backgrounds. This article suggests that the failure to recognize the
      critical link between culture and language (of both the providers and recipients
      of health care) and patient safety stands as a 'resident pathogen' within the
      health care system that, if not addressed, unacceptably exposes patients from
      minority ethno-cultural and language backgrounds to preventable adverse events in
      hospital contexts. It is further suggested that in order to ensure that minority
      as well as majority patient interests in receiving safe and quality care are
      properly protected, the culture-language-patient-safety link needs to be formally
      recognized and the vulnerabilities of patients from minority cultural and
      language backgrounds explicitly identified and actively addressed in patient
      safety systems and processes.

PMID- 16956932
TI  - Persistent hepatitis C virus infection in vitro: coevolution of virus and host.
AB  - The virological and cellular consequences of persistent hepatitis C virus (HCV)
      infection have been elusive due to the absence of the requisite experimental
      systems. Here, we report the establishment and the characteristics of persistent
      in vitro infection of human hepatoma-derived cells by a recently described HCV
      genotype 2a infectious molecular clone. Persistent in vitro infection was
      characterized by the selection of viral variants that displayed accelerated
      expansion kinetics, higher peak titers, and increased buoyant densities.
      Sequencing analysis revealed the selection of a single adaptive mutation in the
      HCV E2 envelope protein that was largely responsible for the variant phenotype.
      In parallel, as the virus became more aggressive, cells that were resistant to
      infection emerged, displaying escape mechanisms operative at the level of viral
      entry, HCV RNA replication, or both. Collectively, these results reveal the
      existence of coevolutionary events during persistent HCV infection that favor
      survival of both virus and host.

PMID- 16956933
TI  - Antibody binding is a dominant determinant of the efficiency of human
      immunodeficiency virus type 1 neutralization.
AB  - Primary and laboratory-adapted variants of human immunodeficiency virus type 1
      (HIV-1) exhibit a wide range of sensitivities to neutralization by antibodies
      directed against the viral envelope glycoproteins. An antibody directed against
      an artificial FLAG epitope inserted into the envelope glycoproteins of three HIV
      1 isolates with vastly different neutralization sensitivities inhibited all three
      viruses equivalently. Thus, naturally occurring HIV-1 isolates that are
      neutralization resistant are not necessarily more impervious to the inhibitory
      consequences of bound antibody. Moreover, the binding affinity of the anti-FLAG
      antibody correlated with neutralizing potency, underscoring the dominant impact
      on neutralization of antibody binding to the envelope glycoproteins.

PMID- 16956934
TI  - Fusion-induced apoptosis contributes to thymocyte depletion by a pathogenic human
      immunodeficiency virus type 1 envelope in the human thymus.
AB  - The mechanisms of CD4(+) T-cell depletion during human immunodeficiency virus
      type 1 (HIV-1) infection remain incompletely characterized. Of particular
      importance is how CD4(+) T cells are depleted within the lymphoid organs,
      including the lymph nodes and thymus. Herein we characterize the pathogenic
      mechanisms of an envelope from a rapid progressor (R3A Env) in the NL4-3 backbone
      (NL4-R3A) which is able to efficiently replicate and deplete CD4(+) thymocytes in
      the human fetal-thymus organ culture (HF-TOC). We demonstrate that uninterrupted
      replication is required for continual thymocyte depletion. During depletion, NL4
      R3A induces an increase in thymocytes which uptake 7AAD, a marker of cell death,
      and which express active caspase-3, a marker of apoptosis. While 7AAD uptake is
      observed predominantly in uninfected thymocytes (p24(-)), active caspase-3 is
      expressed in both infected (p24(+)) and uninfected thymocytes (p24(-)). When
      added to HF-TOC with ongoing infection, the protease inhibitor saquinavir
      efficiently suppresses NL4-R3A replication. In contrast, the fusion inhibitors
      T20 and C34 allow for sustained HIV-1 production. Interestingly, T20 and C34
      effectively prevent thymocyte depletion in spite of this sustained replication.
      Apoptosis of both p24(-) and p24(+) thymocytes appears to be envelope fusion
      dependent, as T20, but not saquinavir, is capable of reducing thymocyte
      apoptosis. Together, our data support a model whereby pathogenic envelope
      dependent fusion contributes to thymocyte depletion in HIV-1-infected thymus,
      correlated with induction of apoptosis in both p24(+) and p24(-) thymocytes.

PMID- 16956935
TI  - Recombination and selection in the evolution of picornaviruses and other
      Mammalian positive-stranded RNA viruses.
AB  - Picornaviridae are a large virus family causing widespread, often pathogenic
      infections in humans and other mammals. Picornaviruses are genetically and
      antigenically highly diverse, with evidence for complex evolutionary histories in
      which recombination plays a major part. To investigate the nature of
      recombination and selection processes underlying the evolution of serotypes
      within different picornavirus genera, large-scale analysis of recombination
      frequencies and sites, segregation by serotype within each genus, and sequence
      selection and composition was performed, and results were compared with those for
      other nonenveloped positive-stranded viruses (astroviruses and human noroviruses)
      and with flavivirus and alphavirus control groups. Enteroviruses, aphthoviruses,
      and teschoviruses showed phylogenetic segregation by serotype only in the
      structural region; lack of segregation elsewhere was attributable to extensive
      interserotype recombination. Nonsegregating viruses also showed several
      characteristic sequence divergence and composition differences between genome
      regions that were absent from segregating virus control groups, such as much
      greater amino acid sequence divergence in the structural region, markedly
      elevated ratios of nonsynonymous-to-synonymous substitutions, and differences in
      codon usage. These properties were shared with other picornavirus genera, such as
      the parechoviruses and erboviruses. The nonenveloped astroviruses and noroviruses
      similarly showed high frequencies of recombination, evidence for positive
      selection, and differential codon use in the capsid region, implying similar
      underlying evolutionary mechanisms and pressures driving serotype
      differentiation. This process was distinct from more-recent sequence evolution
      generating diversity within picornavirus serotypes, in which neutral or purifying
      selection was prominent. Overall, this study identifies common themes in the
      diversification process generating picornavirus serotypes that contribute to
      understanding of their evolution and pathogenicity.

PMID- 16956936
TI  - Human cytomegalovirus tropism for endothelial cells: not all endothelial cells
      are created equal.

PMID- 16956937
TI  - Identification of a novel nonstructural protein, VP9, from white spot syndrome
      virus: its structure reveals a ferredoxin fold with specific metal binding sites.
AB  - White spot syndrome virus (WSSV) is a major pathogen in shrimp aquaculture. VP9,
      a full-length protein of WSSV, encoded by open reading frame wsv230, was
      identified for the first time in the infected Penaeus monodon shrimp tissues,
      gill, and stomach as a novel, nonstructural protein by Western blotting, mass
      spectrometry, and immunoelectron microscopy. Real-time reverse transcription-PCR
      demonstrated that the transcription of VP9 started from the early to the late
      stage of WSSV infection as a major mRNA species. The structure of full-length VP9
      was determined by both X-ray and nuclear magnetic resonance (NMR) techniques. It
      is the first structure to be reported for WSSV proteins. The crystal structure of
      VP9 revealed a ferredoxin fold with divalent metal ion binding sites. Cadmium
      sulfate was found to be essential for crystallization. The Cd2+ ions were bound
      between the monomer interfaces of the homodimer. Various divalent metal ions have
      been titrated against VP9, and their interactions were analyzed using NMR
      spectroscopy. The titration data indicated that VP9 binds with both Zn2+ and
      Cd2+. VP9 adopts a similar fold as the DNA binding domain of the papillomavirus
      E2 protein. Based on our present investigations, we hypothesize that VP9 might be
      involved in the transcriptional regulation of WSSV, a function similar to that of
      the E2 protein during papillomavirus infection of the host cells.

PMID- 16956938
TI  - Cooperative involvement of the S1 and S2 subunits of the murine coronavirus spike
      protein in receptor binding and extended host range.
AB  - To study the process of spike (S)-receptor interaction during coronavirus entry,
      we evaluated the contributions of mutations in different regions of the murine
      hepatitis virus (MHV) S protein to natural receptor murine carcinoembryonic
      antigen-related cell adhesion molecule 1a (CEACAM1a) dependence and to the
      acquisition of extended host range. Extended-host-range variants of MHV strain
      A59 were previously obtained from persistently infected cells (J. H. Schickli, B.
      D. Zelus, D. E. Wentworth, S. G. Sawicki, and K. V. Holmes, J. Virol. 71:9499
      9504, 1997). These variant viruses contain several mutations in the S protein
      that confer to the viruses the ability to enter cells in a heparan sulfate
      dependent manner (C. A. de Haan, Z. Li, E. te Lintelo, B. J. Bosch, B. J.
      Haijema, and P. J. M. Rottier, J. Virol. 79:14451-14456, 2005). While the
      parental MHV-A59 is fully dependent on murine CEACAM1a for its entry, viruses
      carrying the variant mutations in the amino-terminal part of their S protein had
      become dependent on both CEACAM1a and heparan sulfate. Substitutions in a
      restricted, downstream part of the S protein encompassing heptad repeat region 1
      (HR1) and putative fusion peptide (FP) did not alter the CEACAM1a dependence.
      However, when the mutations in both parts of the S protein were combined, the
      resulting viruses became independent of CEACAM1a and acquired the extended host
      range. In addition, these viruses showed a decreased binding to and inhibition by
      soluble CEACAM1a. The observations suggest that the amino-terminal region of the
      S protein, including the receptor-binding domain, and a region in the central
      part of the S protein containing HR1 and FP, i.e., regions far apart in the
      linear sequence, communicate and may even interact physically in the higher-order
      structure of the spike.

PMID- 16956939
TI  - Phospholipase A2 activity-dependent stimulation of Ca2+ entry by human parvovirus
      B19 capsid protein VP1.
AB  - Recent reports demonstrated an association of human parvovirus B19 with
      inflammatory cardiomyopathy (iCMP), which is accompanied by endothelial
      dysfunction. As intracellular Ca(2+) activity is a key regulator of cell function
      and participates in mechanisms leading to endothelial dysfunction, the present
      experiments explored the effects of the B19 capsid proteins VP1 and VP2. A
      secreted phospholipase A2 (PLA2)-like activity has been located in the VP1 unique
      region of the B19 minor capsid protein. As PLA2 has recently been shown to
      activate the store-operated or capacitative Ca(2+) channel I(CRAC), we analyzed
      the impact of the viral PLA2 motif on Ca(2+) entry. We cloned the VP1 and VP2
      genes isolated from a patient suffering from fatal B19 iCMP into eukaryotic
      expression vectors. We also generated a B19 replication-competent plasmid to
      demonstrate PLA2 activity under the control of the complete B19 genome. After the
      transfection of human endothelial cells (HMEC-1), cytosolic Ca(2+) activity was
      determined by utilizing Fura-2 fluorescence. VP1 and VP2 expression did not
      significantly modify basal cytosolic Ca(2+) activity or the decline of cytosolic
      Ca(2+) activity following the removal of extracellular Ca(2+). However,
      expression of VP1 and of the full-length B19 clone, but not of VP2, significantly
      accelerated the increase of cytosolic Ca(2+) activity following the readdition of
      extracellular Ca(2+) in the presence of thapsigargin, indicating an activation of
      I(CRAC.) The effect of VP1 was mimicked by the PLA2 product
      lysophosphatidylcholine and abolished by an inactivating mutation of the PLA2
      encoding region of the VP1 gene. Our observations point to the activation of
      Ca(2+) entry by VP1 PLA2 activity, an effect likely participating in the
      pathophysiology of B19 infection.

PMID- 16956940
TI  - PD-1 expression in acute hepatitis C virus (HCV) infection is associated with HCV
      specific CD8 exhaustion.
AB  - Hepatitis C virus (HCV)-specific CD8 cell exhaustion may represent a mechanism of
      HCV persistence. The inhibitory receptor PD-1 has been reported to be up
      regulated in exhausted CD8 cells. Therefore, we studied PD-1 expression
      longitudinally during acute HCV infection. Most HCV-specific CD8 cells expressed
      PD-1 at the time of acute illness, irrespective of the final outcome. PD-1
      expression declined with the acquisition of a memory phenotype and recovery of an
      efficient CD8 cell function in resolving HCV infections, whereas high levels were
      maintained when HCV persisted and HCV-specific CD8 cells remained dysfunctional.
      Blocking PD-1/PDL-1 interaction with an anti-PDL-1 antibody improved the capacity
      of expansion of virus-specific CD8 cells.

PMID- 16956941
TI  - Interaction of adenovirus type 5 fiber with the coxsackievirus and adenovirus
      receptor activates inflammatory response in human respiratory cells.
AB  - The innate immune response to adenovirus (Ad)-derived gene transfer vectors has
      been shown to initiate immediately after interaction of Ad with respiratory
      epithelial cells, through the induction of extracellular signal-regulated kinase
      1 and 2 (ERK1/2) and JNK mitogen-activated protein kinase (MAPK), nuclear factor
      kappaB (NF-kappaB), and different proinflammatory genes. Ad serotypes 2 or 5
      (Ad2/5) enter respiratory epithelia after initial binding of fiber with the
      coxsackievirus-adenovirus receptor (CAR) or, alternatively, with cell surface
      heparan sulfate glycosaminoglycans. Ad2/5 internalization is triggered by binding
      of penton base to cellular RGD-binding integrins. Here we investigated the role
      of the Ad5 surface domain proteins constituting the vector capsid, namely, the
      fiber, the penton base, and the hexon, on the transmembrane signals leading to
      the transcription of the different proinflammatory genes in the human respiratory
      A549 cell line. Interaction of Ad fiber with CAR activates both ERK1/2 and JNK
      MAPK and the nuclear translocation of NF-kappaB, whereas no activation was
      observed after exposing A549 cells to penton base and hexon proteins. Moreover,
      interaction of Ad fiber with CAR, but not heparan sulfate proteoglycans, promotes
      transcription of the chemokines interleukin-8, GRO-alpha, GRO-gamma, RANTES, and
      interferon-inducible protein 10. These results identify the binding of Ad5 fiber
      with the cellular CAR as a key proinflammatory activation event in epithelial
      respiratory cells that is independent of the transcription of Ad5 genes.

PMID- 16956942
TI  - Kaposi's sarcoma-associated herpesvirus virions inhibit interferon responses
      induced by envelope glycoprotein gpK8.1.
AB  - The Kaposi's sarcoma-associated herpesvirus (KSHV) envelope glycoprotein gpK8.1
      contributes to cellular attachment through binding cell surface heparan sulfate
      proteoglycans. By using a soluble recombinant form of gpK8.1, we discovered that
      a consequence of gpK8.1 interaction with human fibroblasts is the induction of an
      antiviral response, as characterized by the activation of interferon regulatory
      factor 3 (IRF-3), production of interferon beta (IFN-beta), and expression of
      interferon-stimulated antiviral genes. In contrast, neither IFN-beta expression
      nor a functional antiviral response is observed in cells treated with KSHV
      virions. The interferon response induced by soluble gpK8.1 can be inhibited by
      simultaneous treatment with UV-inactivated virions, while the induction of an
      indicator inflammatory cytokine, interleukin-6, was readily evident in the
      response to both gpK8.1 and KSHV. In addition, KSHV virions abrogate gpK8.1
      mediated activation of IRF-3, an early transcriptional regulator for cellular
      antiviral responses. Although innate immune responses are initiated during
      contact between gpK8.1 and cellular receptor(s), these results suggest that the
      virion contains one or more structural elements that selectively repress an
      effective antiviral response while allowing cellular responses favorable to the
      KSHV life cycle.

PMID- 16956943
TI  - Adeno-associated virus type 2 capsids with externalized VP1/VP2 trafficking
      domains are generated prior to passage through the cytoplasm and are maintained
      until uncoating occurs in the nucleus.
AB  - Common features of parvovirus capsids are open pores at the fivefold symmetry
      axes that traverse the virion shell. Upon limited heat treatment in vitro, the
      pores can function as portals to externalize VP1/VP2 protein N-terminal sequences
      which harbor infection-relevant functional domains, such as a phospholipase A(2)
      catalytic domain. Here we show that adeno-associated virus type 2 (AAV2) also
      exposes its VP1/VP2 N termini in vivo during infection, presumably in the
      endosomal compartment. This conformational change is influenced by treatment with
      lysosomotropic reagents. While incubation of cells with bafilomycin A1 reduced
      exposure of VP1/VP2 N termini, incubation with chloroquine stimulated
      externalization transiently. N-terminally located basic amino acid clusters with
      nuclear localization activity also become exposed in this process and are
      accessible on the virus capsid when it enters the cytoplasm. This is an
      obligatory step in AAV2 infection. However, a direct role of these sequences in
      nuclear translocation of viral capsids could not be determined by microinjection
      of wild-type or mutant viruses. This suggests that further modifications of the
      capsid have to take place in a precytoplasmic entry step that prepares the virus
      for nuclear entry. Microinjection of several capsid-specific antibodies into the
      cell nucleus blocked AAV2 infection completely, supporting the conclusion that
      AAV2 capsids bring the infectious genome into the nucleus.

PMID- 16956944
TI  - African swine fever virus causes microtubule-dependent dispersal of the trans
      golgi network and slows delivery of membrane protein to the plasma membrane.
AB  - Viral interference with secretory cargo is a common mechanism for pathogen immune
      evasion. Selective down regulation of critical immune system molecules such as
      major histocompatibility complex (MHC) proteins enables pathogens to mask
      themselves from their host. African swine fever virus (ASFV) disrupts the trans
      Golgi network (TGN) by altering the localization of TGN46, an organelle marker
      for the distal secretory pathway. Reorganization of membrane transport components
      may provide a mechanism whereby ASFV can disrupt the correct secretion and/or
      cell surface expression of host proteins. In the study reported here, we used the
      tsO45 temperature-sensitive mutant of the G protein of vesicular stomatitis virus
      to show that ASFV significantly reduces the rate at which the protein is
      delivered to the plasma membrane. This is linked to a general reorganization of
      the secretory pathway during infection and a specific, microtubule-dependent
      disruption of structural components of the TGN. Golgin p230 and TGN46 are
      separated into distinct vesicles, whereupon TGN46 is depleted. These data suggest
      that disruption of the TGN by ASFV can slow membrane traffic during viral
      infection. This may be functionally important because infection of macrophages
      with virulent isolates of ASFV increased the expression of MHC class I genes, but
      there was no parallel increase in MHC class I molecule delivery to the plasma
      membrane.

PMID- 16956945
TI  - Epstein-Barr virus EBNA-3C is targeted to and regulates expression from the
      bidirectional LMP-1/2B promoter.
AB  - Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA-3C) is essential for EBV
      mediated immortalization of human B lymphocytes and regulates both the cell cycle
      and transcription. Transient reporter gene assays have implicated a pivotal role
      for EBNA-3C in the regulation of transcription of the majority of latency
      associated genes expressed during the EBV growth program, including the viral
      oncoprotein LMP-1. To examine the regulation of latency gene expression by EBNA
      3C, we generated an EBV-positive cell line that inducibly expresses EBNA-3C. This
      cell line allowed us to examine expression from the endogenous latency gene
      promoters in the context of an actual latent infection and the presence of other
      EBNA proteins, in particular EBNA-2, which is presumed to coregulate
      transcription with EBNA-3C. EBNA-3C induced the expression of both LMP-1 and LMP
      2B mRNAs from the bidirectional LMP-1/LMP-2B promoter. In contrast, no effect was
      seen on expression from the common EBNA promoter Cp, which is responsive to EBNA
      3C in reporter assays. Activation of LMP expression was not the consequence of
      increases in EBNA-2, PU.1 or Spi-B transcription factors, all of which are
      believed to be critical for activation of LMP-1. Chromatin immunoprecipitation
      assays furthermore indicated that EBNA-3C is present at the bidirectional LMP
      1/LMP-2B promoter. These results indicate that EBNA-3C directly activates the
      expression of LMP-1 and LMP-2B but is unlikely to significantly regulate EBNA
      expression via Cp under normal growth conditions.

PMID- 16956946
TI  - Differential biophysical properties of infectious intracellular and secreted
      hepatitis C virus particles.
AB  - The recent development of a cell culture infection model for hepatitis C virus
      (HCV) permits the production of infectious particles in vitro. In this report, we
      demonstrate that infectious particles are present both within the infected cells
      and in the supernatant. Kinetic analysis indicates that intracellular particles
      constitute precursors of the secreted infectious virus. Ultracentrifugation
      analyses indicate that intracellular infectious viral particles are similar in
      size (approximately 65 to 70 nm) but different in buoyant density (approximately
      1.15 to 1.20 g/ml) from extracellular particles (approximately 1.03 to 1.16
      g/ml). These results indicate that infectious HCV particles are assembled
      intracellularly and that their biochemical composition is altered during viral
      egress.

PMID- 16956947
TI  - Cyclophilin A, TRIM5, and resistance to human immunodeficiency virus type 1
      infection.

PMID- 16956948
TI  - Sequential turnover of human immunodeficiency virus type 1 env throughout the
      course of infection.
AB  - We examined the rates of variant population turnover of the V1-V2 and V4-V5
      hypervariable domains of the human immunodeficiency virus type 1 (HIV-1) gp120
      molecule in longitudinal plasma samples from 14 men with chronic HIV-1 infection
      using heteroduplex tracking assays (HTA). Six men had high rates of CD4+ T-cell
      loss, and eight men had low rates of CD4+ T-cell loss over 2.5 to 8 years of
      infection. We found that V1-V2 and V4-V5 env populations changed dramatically
      over time in all 14 subjects; the changes in these regions were significantly
      correlated with each another over time. The subjects with rapid CD4 loss had
      significantly less change in their env populations than the subjects with slow
      CD4 loss. The two subjects with rapid CD4 loss and sustained low CD4 counts
      (<150/microl for at least 2 years) showed stabilization of their V1-V2 and V4-V5
      populations as reflected by low levels of total change in HTA pattern and low HTA
      indices (a novel measure of the emergence of new bands and band distribution);
      this stabilization was not observed in other subjects. The stabilization of env
      variant populations at low CD4 counts following periods of rapid viral evolution
      suggests that selective pressure on env, likely from new immune responses, is
      minimal when CD4 counts drop dramatically and remain low for extended periods of
      time.

PMID- 16956950
TI  - In vitro resistance to the human immunodeficiency virus type 1 maturation
      inhibitor PA-457 (Bevirimat).
AB  - 3-O-(3',3'-dimethylsuccinyl)betulinic acid (PA-457 or bevirimat) potently
      inhibits human immunodeficiency virus type 1 (HIV-1) maturation by blocking a
      late step in the Gag processing pathway, specifically the cleavage of SP1 from
      the C terminus of capsid (CA). To gain insights into the mechanism(s) by which
      HIV-1 could evolve resistance to PA-457 and to evaluate the likelihood of such
      resistance arising in PA-457-treated patients, we sought to identify and
      characterize a broad spectrum of HIV-1 variants capable of conferring resistance
      to this compound. Numerous independent rounds of selection repeatedly identified
      six single-amino-acid substitutions that independently confer PA-457 resistance:
      three at or near the C terminus of CA (CA-H226Y, -L231F, and -L231M) and three at
      the first and third residues of SP1 (SP1-A1V, -A3T, and -A3V). We determined that
      mutations CA-H226Y, CA-L231F, CA-L231M, and SP1-A1V do not impose a significant
      replication defect on HIV-1 in culture. In contrast, mutations SP1-A3V and -A3T
      severely impaired virus replication and inhibited virion core condensation. The
      replication defect imposed by SP1-A3V was reversed by a second-site compensatory
      mutation in CA (CA-G225S). Intriguingly, high concentrations of PA-457 enhanced
      the maturation of SP1 residue 3 mutants. The different phenotypes associated with
      mutations that confer PA-457 resistance suggest the existence of multiple
      mechanisms by which HIV-1 can evolve resistance to this maturation inhibitor.
      These findings have implications for the ongoing development of PA-457 to treat
      HIV-1 infection in vivo.

PMID- 16956949
TI  - Human immunodeficiency virus type 1 Vpr induces DNA replication stress in vitro
      and in vivo.
AB  - The human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) causes cell
      cycle arrest in G2. Vpr-expressing cells display the hallmarks of certain forms
      of DNA damage, specifically activation of the ataxia telangiectasia mutated and
      Rad3-related kinase, ATR. However, evidence that Vpr function is relevant in vivo
      or in the context of viral infection is still lacking. In the present study, we
      demonstrate that HIV-1 infection of primary, human CD4+ lymphocytes causes G2
      arrest in a Vpr-dependent manner and that this response requires ATR, as shown by
      RNA interference. The event leading to ATR activation in CD4+ lymphocytes is the
      accumulation of replication protein A in nuclear foci, an indication that Vpr
      likely induces stalling of replication forks. Primary macrophages are refractory
      to ATR activation by Vpr, a finding that is consistent with the lack of
      detectable ATR, Rad17, and Chk1 protein expression in these nondividing cells.
      These observations begin to explain the remarkable resilience of macrophages to
      HIV-1-induced cytopathicity. To study the in vivo consequences of Vpr function,
      we isolated CD4+ lymphocytes from HIV-1-infected individuals and interrogated the
      cell cycle status of anti-p24Gag-immunoreactive cells. We report that infected
      cells in vivo display an aberrant cell cycle profile whereby a majority of cells
      have a 4N DNA content, consistent with the onset of G2 arrest.

PMID- 16956951
TI  - Posttranslational modification and cell type-specific degradation of varicella
      zoster virus ORF29p.
AB  - The ORF29 gene of varicella-zoster virus encodes a single-stranded DNA binding
      protein that is predominantly nuclear during lytic infection but appears to be
      restricted to the cytoplasm of latently infected neurons. Following reactivation,
      ORF29p accumulates in the nuclei of neurons, suggesting that its confinement to
      the cytosol may be critical for maintaining quiescence. When autonomously
      expressed, ORF29p accumulates in the nuclei of fibroblasts and the cytoplasm of
      cells (guinea pig enteric neurons) and cell lines (U373MG) of neuronal origin.
      Inhibition of the 26S proteasome redirects the accumulation of ORF29p to the
      nucleus in cells of neuronal origin. Here, we show that ORF29p is ubiquitinated
      and sumoylated in 293T cells and subsequently degraded from the N terminus.
      Ubiquitinated ORF29p accumulates in both the nuclei and the cytoplasm of
      fibroblasts, but degradation products are seen primarily in the cytoplasm.
      Modification and degradation of ORF29p occurs in 293T, U373MG, and MeWo cells.
      Therefore, these processes are ubiquitous; however, the robustness of the
      degradation process is cell type specific. The proteasome-mediated mechanism of
      nuclear exclusion in U373MG cells is an active process that is not specific for
      the endogenous ORF29p nuclear localization signal but can be saturated by protein
      stabilization or overexpression, which leads to nuclear accumulation of ORF29p.
      The evidence for ORF29p ubiquitination and previous data regarding the effect of
      proteasome inhibitors on the abundance and distribution of ORF29p implicate the
      26S proteasome in influencing the protein's cell type-specific localization.

PMID- 16956952
TI  - Latent Kaposi's sarcoma-associated herpesvirus infection of endothelial cells
      activates hypoxia-induced factors.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV or HHV-8) is the etiological agent
      of Kaposi's sarcoma, a highly vascularized, endothelial-derived tumor. A direct
      role for KSHV-mediated induction of angiogenesis has been proposed based upon the
      nature of the neoplasia and various KSHV gene overexpression and infection model
      systems. We have found that KSHV infection of endothelial cells induces mRNA of
      hypoxia-induced factor 1alpha (HIF1alpha) and HIF2alpha, two homologous alpha
      subunits of the heterodimeric transcription factor HIF. HIF is a master regulator
      of both developmental and pathological angiogenesis, composed of an oxygen
      sensitive alpha subunit and a constitutively expressed beta subunit. HIF is
      classically activated posttranscriptionally with hypoxia, leading to increased
      protein stability of HIF1alpha and/or HIF2alpha. However, we demonstrate that
      both alpha subunits are up-regulated at the transcript level by KSHV infection.
      The transcriptional activation of HIF leads to a functional increase in HIF
      activity under normoxic conditions, as demonstrated by both luciferase reporter
      assay and the increased expression of vascular endothelial growth factor receptor
      1 (VEGFR1), an HIF-responsive gene. KSHV infection synergizes with hypoxia mimics
      and induces higher expression levels of HIF1alpha and HIF2alpha protein, and
      HIF1alpha is increased in a significant proportion of the latently infected
      endothelial cells. Src family kinases are required for the activation of HIF and
      the downstream gene VEGFR1 by KSHV. We also show that KS lesions, in vivo,
      express elevated levels of HIF1alpha and HIF2alpha proteins. Thus, KSHV
      stimulates the HIF pathway via transcriptional up-regulation of both HIF alphas,
      and this activation may play a role in KS formation, localization, and
      progression.

PMID- 16956953
TI  - Signal transduction by human herpesvirus 8 viral interleukin-6 (vIL-6) is
      modulated by the nonsignaling gp80 subunit of the IL-6 receptor complex and is
      distinct from signaling induced by human IL-6.
AB  - Human herpesvirus 8 (HHV-8) viral interleukin-6 (vIL-6) mediates signaling
      through the gp130 signal transducer but unlike human IL-6 (hIL-6) does not
      require the nonsignaling gp80 alpha subunit of the IL-6 receptor complex. By
      utilizing a gp80-refractory vIL-6 variant, vIL-6(R189L), we found that signal
      transduction, as measured by STAT1 and STAT3 activation and gp130 tyrosine
      phosphorylation in gp80+/gp130+ HEK293T cells, was modulated by gp80.
      Furthermore, the signaling and BAF-130 cell growth-promoting activities of vIL-6
      and hIL-6 could be distinguished, and exogenous addition of soluble gp80 enhanced
      cell growth supported by vIL-6. Our findings demonstrate that gp80 can modulate
      vIL-6 activity and that vIL-6 and hIL-6 signaling are not directly equivalent.

PMID- 16956955
TI  - Identification of binding sites of non-I-helix water molecules in mammalian
      cytochromes p450.
AB  - The cytochromes P450 (P450s) enzymes are integral in determining the disposition
      of many therapeutic compounds. At the molecular level, the details of P450
      catalysis are still under investigation, but the importance of water-mediated
      proton shuttles seems evident in the catalytic cycle as it progresses through
      various heme iron-oxygen enzyme intermediates. The study of P450-bound waters has
      been largely restricted to bacterial enzymes that may or may not reflect the
      location or function of waters in human drug-metabolizing P450s. However, in
      recent years, 16 structures of mammalian P450s containing crystallographic waters
      have been deposited in the Protein Data Bank. Described herein is the
      identification of seven well defined water clusters in mammalian P450s identified
      by calculating the density of globally aligned waters as reported by Tanner and
      coworkers [Bottoms CA, White TA, and Tanner JJ (2006) Proteins 64:404-421 (DOI:
      10.1002/prot.21014)]. All water binding sites were in or within the immediate
      vicinity of the active sites of the P450s, but most were not near the conserved I
      helix threonine often implicated in P450 catalysis. Therefore, it is possible
      that some of the water binding sites identified here ultimately determine P450
      catalytic efficiency either by working as an extension of the I-helix water
      network, or by acting in novel proton shuttles that modulate the nonproductive
      shunting of reactive oxygen species.

PMID- 16956956
TI  - Characterization of human urinary metabolites of the antimalarial piperaquine.
AB  - Five metabolites of the antimalarial piperaquine (PQ) (1,3-bis-[4-(7
      chloroquinolyl-4)-piperazinyl-1]-propane) have been identified and their
      molecular structures characterized. After a p.o. dose of dihydroartemisinin
      piperaquine, urine collected over 16 h from two healthy subjects was analyzed
      using liquid chromatography (LC)/UV, LC/tandem mass spectrometry (MS/MS), Fourier
      transform ion cyclotron resonance (FTICR)/MS, and H NMR. Five different peaks
      were recognized as possible metabolites [M1, 320 m/z; M2, M3, and M4, 551 m/z (PQ
      + 16 m/z); and M5, 567 m/z (PQ + 32 m/z)] using LC/MS/MS with gradient elution.
      The proposed carboxylic M1 has a theoretical monoisotopic molecular mass of
      320.1166 m/z, which is in accordance with the FTICR/MS (320.1168 m/z) findings.
      The LC/MS/MS results also showed a 551 m/z metabolite (M2) with a distinct
      difference both in polarity and fragmentation pattern compared with PQ, 7
      hydroxypiperaquine, and the other 551 m/z metabolites. We suggest that this is
      caused by N-oxidation of PQ. The results showed two metabolites (M3 and M4) with
      a molecular ion at 551 m/z and similar fragmentation pattern as both PQ and 7
      hydroxypiperaquine; therefore, they are likely to be hydroxylated PQ metabolites.
      The molecular structures of M1 and M2 were also confirmed using H NMR. Urinary
      excretion rate in one subject suggested a terminal elimination half-life of about
      53 days for M1. Assuming formation rate-limiting kinetics, this would support
      recent findings that the terminal elimination half-life of PQ has been
      underestimated previously.

PMID- 16956954
TI  - Rotavirus anti-VP6 secretory immunoglobulin A contributes to protection via
      intracellular neutralization but not via immune exclusion.
AB  - Immunoglobulin A (IgA) monoclonal antibodies (MAbs) directed at the conserved
      inner core protein VP6 of rotavirus, such as the IgA7D9 MAb, provide protective
      immunity in adult and suckling mice when delivered systemically. While these
      antibodies do not have traditional in vitro neutralizing activity, they could
      mediate their antiviral activity either by interfering with the viral replication
      cycle along the IgA secretory pathway or by acting at mucosal surfaces as
      secretory IgA and excluding virus from target enterocytes. We sought to determine
      the critical step at which antirotaviral activity was initiated by the IgA7D9
      MAb. The IgA7D9 MAb appeared to directly interact with purified triple-layer
      viral particles, as shown by immunoprecipitation and immunoblotting. However,
      protection was not conferred by passively feeding mice with the secretory IgA7D9
      MAb. This indicates that the secretory IgA7D9 MAb does not confer protection by
      supplying immune exclusion activity in vivo. We next evaluated the capacity of
      polymeric IgA7D9 MAb to neutralize rotavirus intracellularly during transcytosis.
      We found that when polymeric IgA7D9 MAb was applied to the basolateral pole of
      polarized Caco-2 intestinal cells, it significantly reduced viral replication and
      prevented the loss of barrier function induced by apical exposure of the cell
      monolayer to rotavirus, supporting the conclusion that the antibody carries out
      its antiviral activity intracellularly. These findings identify a mechanism
      whereby the well-conserved immunodominant VP6 protein can function as a target
      for heterotypic antibodies and protective immunity.

PMID- 16956957
TI  - Pharmacokinetics of berberine and its main metabolites in conventional and pseudo
      germ-free rats determined by liquid chromatography/ion trap mass spectrometry.
AB  - Berberine (Ber) and its main metabolites were identified and quantified using
      liquid chromatography/electrospray ionization/ion trap mass spectrometry. Rat
      plasma contained the main metabolites, berberrubine, thalifendine,
      demethyleneberberine, and jatrorrhizine, as free and glucuronide conjugates after
      p.o. Ber administration. Moreover, the original drug, the four main metabolites,
      and their glucuronide conjugates were all detected in liver tissues after 0.5 h
      and in bile samples 1 h after p.o. Ber administration. Therefore, the metabolic
      site seemed to be the liver, and the metabolites and conjugates were evidently
      excreted into the duodenum as bile. The pharmacokinetics of Ber and the four
      metabolites were determined in conventional and pseudo germ-free rats (treated
      with antibiotics) after p.o. administration with 40 mg/kg Ber. The AUC0-limt and
      mean transit time values of the metabolites significantly differed between
      conventional and pseudo germ-free rats. The amounts of metabolites were
      remarkably reduced in the pseudo germ-free rats, whereas levels of Ber did not
      obviously differ between the two groups. The intestinal flora did not exert
      significant metabolic activity against Ber and its metabolites, but it played a
      significant role in the enterohepatic circulation of metabolites. In this sense,
      the liver and intestinal bacteria participate in the metabolism and disposition
      of Ber in vivo.

PMID- 16956958
TI  - Old and ill and still feeling well? Determinants of subjective well-being in
      >or=60 year olds: the role of the sense of coherence.
AB  - OBJECTIVE: The authors investigated the determinants of subjective well-being in
      a sample of elderly by applying a salutogenetic model of subjective well-being in
      which sense of coherence (SOC) plays a central role. The hypothesis was that
      subjective evaluation and SOC as a personality resource explain more variance of
      subjective well-being than the objective changes resulting from the aging
      process. METHODS: A sample of >or=60-year-old patients of an internal hospital,
      previously examined between 1994 and 1997, were once more contacted between 2000
      and 2002. Fifty-six patients were investigated by means of psychometric scales
      and biographic interviews. Compared with the sample of the first investigation, a
      positive selection effect could be found for the sample of the present
      investigation with regard to age- and health-related variables, however, not with
      regard to subjective well-being. A path model formulated in advance was tested.
      RESULTS: Despite an increase in physical disability, subjective well-being
      remained constant for both points in time. The path model supported the
      hypothesis that subjective well-being at the second measurement point was hardly
      influenced by "objective" conditions of aging and functional impairment but was
      significantly influenced by the individual's subjective evaluation of the present
      situation as well as the sense of coherence. CONCLUSIONS: Our results support a
      salutogenetic model of subjective well-being in our sample; these findings
      should, however, be replicated in other samples.

PMID- 16956959
TI  - APOE genotype and cholesterol levels in lewy body dementia and Alzheimer disease:
      investigating genotype-phenotype effect on disease risk.
AB  - BACKGROUND: APOE is the most recognized genetic risk factor for sporadic late
      onset Alzheimer disease (AD). The role of APOE genotype in Lewy body dementia
      (LBD) is still unknown as well as the relationship between APOE genotype and
      cholesterol levels. OBJECTIVE: The objective of this study was to explore the
      association between APOE genotype and cholesterol levels in patients with LBD and
      those with AD. METHODS: Eighty-two patients with LBD were consecutively enrolled
      as well as a comparable number of patients with AD and comparison group. Each
      subject underwent a clinical and neuropsychologic evaluation and APOE genotyping.
      RESULTS: The distribution of APOE genotypes significantly differed between AD and
      LBD cases compared with the comparison group, with the APOE epsilon4+
      (epsilon4+/epsilon4 + or epsilon4+/epsilon4-) genotype more frequent in patient
      subgroups. Different models have been fitted, and total APOE epsilon4
      hypercholesterolemia complete interaction effect was claimed in predicting their
      relationship on disease outcome. Subjects with hypercholesterolemia and
      heterozygous for APOE epsilon4 allele had more than threefold risk to develop AD
      compared both with the comparison group and with those with LBD. The risk to
      develop AD in hypercholesterolemic and APOE epsilon4 homozygous subjects was 13
      fold compared with the comparison group and those with LBD. Conversely, there was
      not evidence for APOE epsilon4-hypercholesterolemia complete interaction effect
      in LBD and in the comparison group. CONCLUSIONS: This study highlighted that APOE
      is a risk factor not only for AD, but also for LBD, and that the APOE-cholesterol
      pathway differently affects AD and LBD. This approach may aid the search for the
      identification of an interactive effect of APOE genotype and modifiable risk
      factors, i.e., hypercholesterolemia, eventually resulting in individualized and
      effective cholesterol-lowering therapy in at-risk subjects.

PMID- 16956960
TI  - Altitude above sea level as a variable for definition of anemia.

PMID- 16956961
TI  - Taurine transporter in fetal T lymphocytes and platelets: differential expression
      and functional activity.
AB  - Transplacental transfer of taurine, a beta-amino acid essential for fetal and
      neonatal development, constitutes the primary source of taurine for the fetus.
      Placental transport of taurine is compromised in pregnancies complicated by
      intrauterine growth restriction, resulting in a reduced concentration of taurine
      in cord plasma. This could impact on fetal cellular metabolism as taurine
      represents the most abundant intracellular amino acid in many fetal cell types.
      In the present study, we have used pure isolates of fetal platelets and T
      lymphocytes from cord blood of placentas, from normal, term pregnancies, as fetal
      cell types to examine the cellular uptake mechanisms for taurine by the system
      beta transporter and have compared gene and protein expression for the taurine
      transporter protein (TAUT) in these two cell types. System beta activity in fetal
      platelets was 15-fold higher compared with fetal T lymphocytes (P < 0.005),
      mirroring greater TAUT mRNA expression in platelets than T lymphocytes (P <
      0.005). Cell-specific differences in TAUT protein moieties were detected with a
      doublet of 75 and 80 kDa in fetal platelets compared with 114 and 120 kDa in
      fetal T lymphocytes, with relatively higher expression in platelets. We conclude
      that greater system beta activity in fetal platelets compared with T lymphocytes
      is the result of relatively greater TAUT mRNA and protein expression. This study
      represents the first characterization of amino acid transporters in fetal T
      lymphocytes.

PMID- 16956962
TI  - Multiple repressor pathways contribute to phenotypic switching of vascular smooth
      muscle cells.
AB  - Smooth muscle cell (SMC) differentiation is an essential component of vascular
      development and these cells perform biosynthetic, proliferative, and contractile
      roles in the vessel wall. SMCs are not terminally differentiated and possess the
      ability to modulate their phenotype in response to changing local environmental
      cues. The focus of this review is to provide an overview of the current state of
      knowledge of molecular mechanisms involved in controlling phenotypic switching of
      SMC with particular focus on examination of processes that contribute to the
      repression of SMC marker genes. We discuss the environmental cues which actively
      regulate SMC phenotypic switching, such as platelet-derived growth factor-BB, as
      well as several important regulatory mechanisms required for suppressing
      expression of SMC-specific/selective marker genes in vivo, including those
      dependent on conserved G/C-repressive elements, and/or highly conserved
      degenerate CArG elements found in the promoters of many of these marker genes.
      Finally, we present evidence indicating that SMC phenotypic switching involves
      multiple active repressor pathways, including Kruppel-like zinc finger type 4,
      HERP, and ERK-dependent phosphorylation of Elk-1 that act in a complementary
      fashion.

PMID- 16956963
TI  - Distinct roles of PMCA isoforms in Ca2+ homeostasis of bladder smooth muscle:
      evidence from PMCA gene-ablated mice.
AB  - We previously showed that plasma membrane Ca(2+)-ATPase (PMCA) activity accounted
      for 25-30% of relaxation in bladder smooth muscle (8). Among the four PMCA
      isoforms only PMCA1 and PMCA4 are expressed in smooth muscle. To address the role
      of these isoforms, we measured cytosolic Ca(2+) ([Ca(2+)](i)) using fura-PE3 and
      simultaneously measured contractility in bladder smooth muscle from wild-type
      (WT), Pmca1(+/-), Pmca4(+/-), Pmca4(-/-), and Pmca1(+/-)Pmca4(-/-) mice. There
      were no differences in basal [Ca(2+)](i) values between bladder preparations. KCl
      (80 mM) elicited both larger forces (150-190%) and increases in [Ca(2+)](i) (130
      180%) in smooth muscle from Pmca1(+/-) and Pmca1(+/-)Pmca4(-/-) bladders than
      those in WT or Pmca4(-/-). The responses to carbachol (CCh: 10 muM) were also
      greater in Pmca1(+/-) (120-150%) than in WT bladders. In contrast, the responses
      in Pmca4(-/-) and Pmca1(+/-)Pmca4(-/-) bladders to CCh were significantly smaller
      (40-50%) than WT. The rise in half-times of force and [Ca(2+)](i) increases in
      response to KCl and CCh, and the concomitant half-times of their decrease upon
      washout of agonist were prolonged in Pmca4(-/-) (130-190%) and Pmca1(+/-)Pmca4(-/
      ) (120-250%) bladders, but not in Pmca1(+/-) bladders with respect to WT. Our
      evidence indicates distinct isoform functions with the PMCA1 isoform involved in
      overall Ca(2+) clearance, while PMCA4 is essential for the [Ca(2+)](i) increase
      and contractile response to the CCh receptor-mediated signal transduction
      pathway.

PMID- 16956964
TI  - SCAM analysis reveals a discrete region of the pore turret that modulates slow
      inactivation in Kv1.5.
AB  - In Kv1.5, protonation of histidine 463 in the S5-P linker (turret) increases the
      rate of depolarization-induced inactivation and decreases the peak current
      amplitude. In this study, we examined how amino acid substitutions that altered
      the physico-chemical properties of the side chain at position 463 affected slow
      inactivation and then used the substituted cysteine accessibility method (SCAM)
      to probe the turret region (E456-P468) to determine whether residue 463 was
      unique in its ability to modulate the macroscopic current. Substitutions at
      position 463 of small, neutral (H463G and H463A) or large, charged (H463R, H463K,
      and H463E) side groups accelerated inactivation and induced a dependency of the
      current amplitude on the external potassium concentration. When cysteine
      substitutions were made in the distal turret (T462C-P468C), modification with
      either the positively charged [2-(trimethylammonium)ethyl] methanethiosulfonate
      bromide (MTSET) or negatively charged sodium (2-sulfonatoethyl)
      methanethiosulfonate reagent irreversibly inhibited current. This inhibition
      could be antagonized either by the R487V mutation (homologous to T449V in Shaker)
      or by raising the external potassium concentration, suggesting that current
      inhibition by MTS reagents resulted from an enhancement of inactivation. These
      results imply that protonation of residue 463 does not modulate inactivation
      solely by an electrostatic interaction with residues near the pore mouth, as
      proposed by others, and that residue 463 is part of a group of residues within
      the Kv1.5 turret that can modulate P/C-type inactivation.

PMID- 16956965
TI  - Episodic ataxia type 1 mutation F184C alters Zn2+-induced modulation of the human
      K+ channel Kv1.4-Kv1.1/Kvbeta1.1.
AB  - Episodic ataxia type 1 (EA1) is a Shaker-like channelopathy characterized by
      continuous myokymia and attacks of imbalance with jerking movements of the head,
      arms, and legs. Although altered expression and gating properties of Kv1.1
      channels underlie EA1, several disease-causing mechanisms remain poorly
      understood. It is likely that Kv1.1, Kv1.4, and Kvbeta1.1 subunits form
      heteromeric channels at hippocampal mossy fiber boutons from which Zn(2+) ions
      are released into the synaptic cleft in a Ca(2+)-dependent fashion. The
      sensitivity of this macromolecular channel complex to Zn(2+) is unknown. Here, we
      show that this heteromeric channel possesses a high-affinity (<10 muM) and a low
      affinity (<0.5 mM) site for Zn(2+), which are likely to regulate channel
      availability at distinct presynaptic membranes. Furthermore, the EA1 mutation
      F184C, located within the S1 segment of the Kv1.1 subunit, markedly decreased the
      equilibrium dissociation constants for Zn(2+) binding to the high- and low
      affinity sites. The functional characterization of the Zn(2+) effects on
      heteromeric channels harboring the F184C mutation also showed that this ion
      significantly 1) slowed the activation rate of the channel, 2) increased the time
      to reach peak current amplitude, 3) decreased the rate and amount of current
      undergoing N-type inactivation, and 4) slowed the repriming of the channel
      compared with wild-type channels. These results demonstrate that the EA1 mutation
      F184C will not only sensitize the homomeric Kv1.1 channel to extracellular
      Zn(2+), but it will also endow heteromeric channels with a higher sensitivity to
      this metal ion. During the vesicular release of Zn(2+), its effects will be in
      addition to the intrinsic gating defects caused by the mutation, which is likely
      to exacerbate the symptoms by impairing the integration and transmission of
      signals within specific brain areas.

PMID- 16956966
TI  - Imaging of respiratory-related population activity with single-cell resolution.
AB  - The pre-Botzinger complex (PBC) in the rostral ventrolateral medulla contains a
      kernel involved in respiratory rhythm generation. So far, its respiratory
      activity has been analyzed predominantly by electrophysiological approaches.
      Recent advances in fluorescence imaging now allow for the visualization of
      neuronal population activity in rhythmogenic networks. In the respiratory
      network, voltage-sensitive dyes have been used mainly, so far, but their low
      sensitivity prevents an analysis of activity patterns of single neurons during
      rhythmogenesis. We now have succeeded in using more sensitive Ca(2+) imaging to
      study respiratory neurons in rhythmically active brain stem slices of neonatal
      rats. For the visualization of neuronal activity, fluo-3 was suited best in terms
      of neuronal specificity, minimized background fluorescence, and response
      magnitude. The tissue penetration of fluo-3 was improved by hyperosmolar
      treatment (100 mM mannitol) during dye loading. Rhythmic population activity was
      imaged with single-cell resolution using a sensitive charge-coupled device camera
      and a x20 objective, and it was correlated with extracellularly recorded mass
      activity of the contralateral PBC. Correlated optical neuronal activity was
      obvious online in 29% of slices. Rhythmic neurons located deeper became
      detectable during offline image processing. Based on their activity patterns, 74%
      of rhythmic neurons were classified as inspiratory and 26% as expiratory neurons.
      Our approach is well suited to visualize and correlate the activity of several
      single cells with respiratory network activity. We demonstrate that neuronal
      synchronization and possibly even network configurations can be analyzed in a
      noninvasive approach with single-cell resolution and at frame rates currently not
      reached by most scanning-based imaging techniques.

PMID- 16956967
TI  - Calcium controls smooth muscle TRPC gene transcription via the CaMK/calcineurin
      dependent pathways.
AB  - Transient receptor potential protein family C (TRPC) has been proposed as a
      candidate for channels involved in capacitative Ca(2+) entry (CCE) mechanisms,
      but the modulation of their gene expression remains unexplored. In this study we
      show that guinea pig gallbladder smooth muscle contains mRNA encoding TRPC1,
      TRPC2, TRPC3, and TRPC4 proteins whose abundance depends on cytosolic Ca(2+)
      level ([Ca(2+)](i)). Thus lowering the levels of cellular calcium with the
      chelators EGTA and BAPTA AM results in a downregulation of TRPC1-TRPC4 gene and
      protein expression. In contrast, activation of Ca(2+) influx through L-type
      Ca(2+) channels and Ca(2+) release from intracellular stores induced an increase
      in TRPC1-TRPC4 mRNA and protein abundance. Activation of Ca(2+)/calmodulin
      dependent kinases (CaMK) and phosphorylation of cAMP-response element binding
      protein accounts for the increase in TRPC mRNA transcription in response to L
      type channel-mediated Ca(2+) influx . In addition to this mechanism, activation
      of TRPC gene expression by intracellular Ca(2+) release also involves calcineurin
      pathway. According to the proposed role for these channels, activation of CCE
      induced an increase in TRPC1 and TRPC3 mRNA abundance, which depends on the
      integrity of the calcineurin and CaMK pathways. These findings show for the first
      time an essential autoregulatory role of Ca(2+) in Ca(2+) homeostasis at the
      level of TRPC gene and protein expression.

PMID- 16956968
TI  - Exogenous sphingosine 1-phosphate and sphingosine kinase activated by endothelin
      1 induced myometrial contraction through differential mechanisms.
AB  - Sphingosine 1-phosphate (S1P), a bioactive sphingolipid involved in diverse
      biological processes, is generated by sphingosine kinase (SphK) and acts via
      intracellular and/or extracellular mechanisms. We used biochemical,
      pharmacological, and physiological approaches to investigate in rat myometrium
      the contractile effect of exogenous S1P and the possible contribution of SphK in
      endothelin-1 (ET-1)-mediated contraction. S1P stimulated uterine contractility
      (EC(50) = 1 microM and maximal response = 5 microM) by a pertussis toxin
      insensitive and a phospholipse C (PLC)-independent pathway. Phosphorylated
      FTY720, which interacts with all S1P receptors, except S1P(2) receptors, failed
      to mimic S1P contractile response, indicating that the effects of S1P involved
      S1P(2) receptors that are expressed in myometrium. Contraction mediated by S1P
      and ET-1 required extracellular calcium and Rho kinase activation. Inhibition of
      SphK reduced ET-1-mediated contraction. ET-1, via ET(A) receptors coupled to
      pertussis toxin-insensitive G proteins, stimulated SphK1 activity and induced its
      translocation to the membranes. Myometrial contraction triggered by ET-1 is
      consecutive to the sequential activation of PLC, protein kinase C, SphK1 and Rho
      kinase. Prolonged exposure of the myometrium to S1P downregulated S1P(2)
      receptors and abolished the contraction induced by exogenous S1P. However, in
      these conditions, the tension triggered by ET-1 was not reduced, indicating that
      SphK activated by ET-1 contributed to its contractile effect via a S1P(2)
      receptor-independent process. Our findings demonstrated that exogenous S1P and
      SphK activity regulated myometrial contraction and may be of physiological
      relevance in the regulation of uterine motility during gestation and parturition.

PMID- 16956969
TI  - Profound bilateral sensorineural hearing loss in nigerian children: any shift in
      etiology?
AB  - Deafness, profound hearing loss, is a global problem. However, the causes of,
      attitudes toward, and management options for deafness differ considerably from
      region to region. This study seeks to identify the present causes of profound
      sensorineural hearing loss in Nigeria, which in our environment is almost
      synonymous to a life sentence of silence and isolation. This is a retrospective
      survey of children 15 years and below (M = 6.7 years, SD = 3.2). Of the 115
      children included in this study, 64 (55.7%) were males, giving a male:female
      ratio of 5:4. Age group 1-3 years had the highest proportion of hearing loss, 33
      (28.7%), and there was a progressive decline in frequency with advancing age. In
      about a third (34.8%) of patients, causes were unknown, probably congenital. The
      main acquired causes were febrile illness (18.3%), measles (13.9%), meningitis
      (8.7%), mumps (6.9%), or severe birth asphyxia (4.3%). Compared to the findings
      of two decades ago, we conclude that there is no significant shift yet in the
      etiology of profound sensorineural hearing loss in our environment.

PMID- 16956970
TI  - Depression of gustatory receptor potential in frog taste cell by parasympathetic
      nerve-induced slow hyperpolarizing potential.
AB  - Parasympathetic nerve (PSN) innervates taste cells of the frog taste disk, and
      electrical stimulation of PSN elicited a slow hyperpolarizing potential (HP) in
      taste cells. Here we report that gustatory receptor potentials in frog taste
      cells are depressed by PSN-induced slow HPs. When PSN was stimulated at 30 Hz
      during generation of taste cell responses, the large amplitude of depolarizing
      receptor potential for 1 M NaCl and 1 mM acetic acid was depressed by
      approximately 40% by slow HPs, but the small amplitude of the depolarizing
      receptor potential for 10 mM quinine-HCl (Q-HCl) and 1 M sucrose was completely
      depressed by slow HPs and furthermore changed to the hyperpolarizing direction.
      The duration of the depolarizing receptor potentials depressed by slow HPs
      prolonged with increasing period of PSN stimulation. As tastant-induced
      depolarizing receptor potentials were increased, the amplitude of PSN-induced
      slow HPs inhibiting the receptor potentials gradually decreased. The mean
      reversal potentials of the slow HPs were approximately -1 mV under NaCl and
      acetic acid stimulations, but approximately -14 mV under Q-HCl and sucrose
      stimulations. This implies that when a slow HP was evoked on the same amplitude
      of depolarizing receptor potentials, the depression of the NaCl and acetic acid
      responses in taste cells was larger than that of Q-HCl and sucrose responses. It
      is concluded that slow HP-induced depression of gustatory depolarizing receptor
      potentials derives from the interaction between gustatory receptor current and
      slow hyperpolarizing current in frog taste cells and that the interaction is
      stronger for NaCl and acetic acid stimulations than for Q-HCl and sucrose
      stimulations.

PMID- 16956971
TI  - Recognition of T-rich single-stranded DNA by the cold shock protein Bs-CspB in
      solution.
AB  - Cold shock proteins (CSP) belong to the family of single-stranded nucleic acid
      binding proteins with OB-fold. CSP are believed to function as 'RNA chaperones'
      and during anti-termination. We determined the solution structure of Bs-CspB
      bound to the single-stranded DNA (ssDNA) fragment heptathymidine (dT7) by NMR
      spectroscopy. Bs-CspB reveals an almost invariant conformation when bound to dT7
      with only minor reorientations in loop beta1-beta2 and beta3-beta4 and of few
      aromatic side chains involved in base stacking. Binding studies of protein
      variants and mutated ssDNA demonstrated that Bs-CspB associates with ssDNA at
      almost diffusion controlled rates and low sequence specificity consistent with
      its biological function. A variation of the ssDNA affinity is accomplished solely
      by changes of the dissociation rate. 15N NMR relaxation and H/D exchange
      experiments revealed that binding of dT7 increases the stability of Bs-CspB and
      reduces the sub-nanosecond dynamics of the entire protein and especially of loop
      beta3-beta4.

PMID- 16956972
TI  - Evolution of the terminal regions of the Streptomyces linear chromosome.
AB  - Comparative analysis of the Streptomyces chromosome sequences, between
      Streptomyces coelicolor, Streptomyces avermitilis, and Streptomyces ambofaciens
      ATCC23877 (whose partial sequence is released in this study), revealed a highly
      compartmentalized genetic organization of their genome. Indeed, despite the
      presence of specific genomic islands, the central part of the chromosome appears
      highly syntenic. In contrast, the chromosome of each species exhibits large
      species-specific terminal regions (from 753 to 1,393 kb), even when considering
      closely related species (S. ambofaciens and S. coelicolor). Interestingly, the
      size of the central conserved region between species decreases as the
      phylogenetic distance between them increases, whereas the specific terminal
      fraction reciprocally increases in size. Between highly syntenic central regions
      and species-specific chromosomal parts, there is a notable degeneration of
      synteny due to frequent insertions/deletions. This reveals a massive and constant
      genomic flux (from lateral gene transfer and DNA rearrangements) affecting the
      terminal contingency regions. We speculate that a gradient of recombination rate
      (i.e., insertion/deletion events) toward the extremities is the force driving the
      exclusion of essential genes from the terminal regions (i.e., chromosome
      compartmentalization) and generating a fast gene turnover for strong adaptation
      capabilities.

PMID- 16956973
TI  - Robustness of coalescent estimators to between-lineage mutation rate variation.
AB  - Data from HIV and from human neoplastic cells can show substantial between
      lineage mutation rate variation even within a single population. Such variation
      may affect estimators of population quantities such as Theta = 4N(e)mu. Using
      simulated DNA data, I measured the effect of rate variation on recovery of Theta
      by the summary-statistic estimator of Watterson (Watterson GA. 1975. On the
      number of segregating sites in genetical systems without recombination. Theor
      Popul Biol. 7:256-276) and the coalescent maximum likelihood algorithm LAMARC
      (Kuhner MK. 2006. LAMARC 2.0: maximum likelihood and Bayesian estimation of
      population parameters. Bioinformatics. Advance Access doi:
      10.1093/bioinformatics/btk051). Watterson's estimator showed a downward bias, as
      expected, with high values of Theta. LAMARC's mean estimate was accurate for all
      tested values of Theta and rate variation except for a downward bias when rate
      variation was maximal (i.e., the slow rate was zero). LAMARC had consistently
      narrower confidence intervals (CIs) than Watterson's estimator. Both methods
      tended to reject the truth too often when rate variation was 8x or greater and
      independent among branches, as well as when variation was 4x or greater and
      correlated among branches. In the case of Watterson's estimate, this excess
      rejection was fully attributable to variation among genealogies in the amount of
      total branch length associated with the fast and slow rates. However, in the case
      of LAMARC, some excess rejection was still observed even when between-genealogy
      variation was taken into account. Both estimators are robust to modest rate
      variation; however, their use should be coupled with a statistical test to rule
      out extreme rate variation as the resulting CIs may not be reliable.

PMID- 16956974
TI  - Difference between evolutionarily effective and germ line mutation rate due to
      stochastically varying haplogroup size.
AB  - Within a Y-chromosome haplogroup defined by unique event mutations, variation in
      microsatellites can accumulate due to their rapid mutation. Estimates based on
      pedigrees for the Y-chromosome microsatellite mutation rate are 3 or more times
      greater than the same estimates from evolutionary considerations. We show by
      simulation that the haplogroups that survive the stochastic processes of drift
      and extinction accumulate microsatellite variation at a lower rate than predicted
      from corresponding pedigree estimates; in particular, under constant total
      population size, the accumulated variance is on average 3-4 times smaller.

PMID- 16956975
TI  - Feature-selective attention enhances color signals in early visual areas of the
      human brain.
AB  - We used an electrophysiological measure of selective stimulus processing (the
      steady-state visual evoked potential, SSVEP) to investigate feature-specific
      attention to color cues. Subjects viewed a display consisting of spatially
      intermingled red and blue dots that continually shifted their positions at
      random. The red and blue dots flickered at different frequencies and thereby
      elicited distinguishable SSVEP signals in the visual cortex. Paying attention
      selectively to either the red or blue dot population produced an enhanced
      amplitude of its frequency-tagged SSVEP, which was localized by source modeling
      to early levels of the visual cortex. A control experiment showed that this
      selection was based on color rather than flicker frequency cues. This signal
      amplification of attended color items provides an empirical basis for the rapid
      identification of feature conjunctions during visual search, as proposed by
      "guided search" models.

PMID- 16956977
TI  - Direct screening of solution phase combinatorial libraries encoded with
      externally sensitized photolabile tags.
AB  - Solution phase combinatorial chemistry holds an enormous promise for modern drug
      discovery. Much needed are direct methods to assay such libraries for binding of
      biological targets. An approach to encoding and screening of solution phase
      libraries has been developed based on the conditional photorelease of externally
      sensitized photolabile tags. The encoding tags are released into solution only
      when a sought-for binding event occurs between the ligand and the receptor,
      outfitted with an electron-transfer sensitizer. The released tags are analyzed in
      solution revealing the identity of the lead ligand or narrowing the range of
      potential leads.

PMID- 16956976
TI  - Crystal structure of human histone lysine-specific demethylase 1 (LSD1).
AB  - Lysine-specific demethylase 1 (LSD1) was recently identified as the first histone
      demethylase that specifically demethylates monomethylated and dimethylated
      histone H3 at K4. It is a component of the CoREST and other corepressor complexes
      and plays an important role in silencing neuronal-specific genes in nonneuronal
      cells, but the molecular mechanisms of its action remain unclear. The 2.8-A
      resolution crystal structure of the human LSD1 reveals that LSD1 defines a new
      subfamily of FAD-dependent oxidases. The active center of LSD1 is characterized
      by a remarkable 1,245-A3 substrate-binding cavity with a highly negative
      electrostatic potential. Although the protein core of LSD1 resembles other
      flavoenzymes, its enzymatic activity and functions require two additional
      structural modules: an N-terminal SWIRM domain important for protein stability
      and a large insertion in the catalytic domain indispensable both for the
      demethylase activity and the interaction with CoREST. These results provide a
      framework for further probing the catalytic mechanism and the functional roles of
      LSD1.

PMID- 16956978
TI  - Differential sensitivity to words and shapes in ventral occipito-temporal cortex.
AB  - Efficient extraction of shape information is essential for proficient reading but
      the role of cortical mechanisms of shape analysis in word reading is not well
      understood. We studied cortical responses to written words while parametrically
      varying the amount of visual noise applied to the word stimuli. In only a few
      regions along the ventral surface, cortical responses increased with word
      visibility. We found consistently increasing responses in bilateral posterior
      occipito-temporal sulcus (pOTS), at an anatomical location that closely matches
      the "visual word form area". In other cortical regions, such as V1, responses
      remained constant regardless of the noise level. We performed 3 additional tests
      to assess the functional specialization of pOTS responses for written word
      processing. We asked whether pOTS responses are 1) left lateralized, 2) more
      sensitive to words than to line drawings or false fonts, and 3) invariant for
      visual hemifield of words but not other stimuli. We found that left and right
      pOTS response functions both had highest sensitivity for words, intermediate for
      line drawings, and lowest for false fonts. Visual hemifield invariance was
      similar for words and line drawings. These results suggest that left and right
      pOTS are both involved in shape processing, with enhanced efficiency for
      processing visual word forms.

PMID- 16956979
TI  - Error-likelihood prediction in the medial frontal cortex: a critical evaluation.
AB  - A recent study has proposed that posterior regions of the medial frontal cortex
      (pMFC) learn to predict the likelihood of errors occurring in a given task
      context. A key prediction of the error-likelihood (EL) hypothesis is that the
      pMFC should exhibit enhanced activity to cues that are predictive of high
      compared with low error rates. We conducted 3 experiments, 2 using functional
      neuroimaging and 1 using event-related potentials, to test this prediction in
      human volunteers. The 3 experiments replicated previous research in showing clear
      evidence of increased pMFC activity associated with errors, conflict, negative
      feedback, and other aspects of task performance. However, none of the experiments
      yielded evidence for an effect of cue-signaled EL on pMFC activity or any
      indication that such an effect developed with learning. We conclude that although
      the EL hypothesis presents an elegant integrative account of pMFC function, it
      requires additional empirical support to remain tenable.

PMID- 16956980
TI  - Neural processing of fearful faces: effects of anxiety are gated by perceptual
      capacity limitations.
AB  - Debate continues as to the automaticity of the amygdala's response to threat.
      Accounts taking a strong automaticity line suggest that the amygdala's response
      to threat is both involuntary and independent of attentional resources. Building
      on these accounts, prominent models have suggested that anxiety modulates the
      output of an amygdala-based preattentive threat evaluation system. Here, we argue
      for a modification of these models. Functional magnetic resonance imaging data
      were collected while volunteers performed a letter search task of high or low
      perceptual load superimposed on fearful or neutral face distractors. Neither high
      nor low-anxious volunteers showed an increased amygdala response to threat
      distractors under high perceptual load, contrary to a strong automaticity account
      of amygdala function. Under low perceptual load, elevated state anxiety was
      associated with a heightened response to threat distractors in the amygdala and
      superior temporal sulcus, whereas individuals high in trait anxiety showed a
      reduced prefrontal response to these stimuli, consistent with weakened
      recruitment of control mechanisms used to prevent the further processing of
      salient distractors. These findings suggest that anxiety modulates processing
      subsequent to competition for perceptual processing resources, with state and
      trait anxiety having distinguishable influences upon the neural mechanisms
      underlying threat evaluation and "top-down" control.

PMID- 16956981
TI  - Effects of analgesic or antidepressant drugs on pain- or stress-evoked
      hippocampal and spinal neurokinin-1 receptor and brain-derived neurotrophic
      factor gene expression in the rat.
AB  - Clinical studies show that people suffering from chronic pain are often also
      burdened by depression. Antidepressants are used to treat some types of chronic
      pain; however, little is known about their mechanisms of action. This study
      addressed the effects of a nonsteroidal anti-inflammatory drug and a tricyclic
      antidepressant drug on pain- and stress-evoked gene expression in the rat spinal
      cord dorsal horn and hippocampus. Rats were pretreated with either indomethacin
      or imipramine and then challenged with either intraplantar complete Freund's
      adjuvant or a bout of immobilization stress. Results showed that indomethacin
      significantly reduced nociception-related peripheral edema, hyperalgesia, and
      reversed the pain-evoked up-regulation of neurokinin (NK)-1 receptor and brain
      derived neurotrophic factor (BDNF) gene expression in the spinal cord to levels
      not statistically different from controls. However, indomethacin did not protect
      against significant pain-induced down-regulation of these genes in the
      hippocampus by approximately 50%, suggesting that although analgesic drug
      treatment reduces nociceptive sensory activation in the spinal cord, it is
      insufficient to prevent the impact of pain on the hippocampus. Conversely,
      although imipramine did not provide significant behavioral analgesia, it
      significantly blocked both pain- and stress-evoked alterations in hippocampal and
      spinal NK-1 and BDNF gene expression. Thus, these results show that application
      of either analgesic or antidepressant drugs alone does not fully protect against
      both the behavioral and molecular effects of persistent pain on both "sensory"
      and "affective" processing within the central nervous system.

PMID- 16956982
TI  - Differential responses of corticotropin-releasing hormone receptor type 1
      variants to protein kinase C phosphorylation.
AB  - Corticotropin-releasing hormone (CRH) regulates diverse biological functions in
      mammals, through activation of two types of specific G protein-coupled receptors
      that are expressed as multiple mRNA spliced variants. In most cells, the type
      1alpha CRH receptor (CRH-R1alpha) preferentially activates the G(s)-adenylyl
      cyclase signaling cascade. CRH-R1alpha-mediated signaling activity is impaired by
      insertion of 29 amino acids in the first intracellular loop, a sequence
      modification that is characteristic of the human-specific CRH-R1beta variant. In
      various tissues, CRH signaling events are regulated by protein kinase C (PKC).
      The CRH receptors contain multiple putative PKC phosphorylation sites that
      represent potential targets. To investigate this, we expressed recombinant CRH
      R1alpha or CRH-R1beta in human embryonic kidney 293 cells and analyzed signaling
      events after PKC activation. Agonist (oxytocin) or phorbol 12-myristate 13
      acetate-induced activation of PKC led to phosphorylation of both CRH-R1 variants.
      However, CRH-R1alpha and CRH-R1beta exhibited different functional responses to
      PKC-induced phosphorylation, with only the CRH-R1beta susceptible to cAMP
      signaling desensitization. This was associated with a significant decrease of
      accessible CRH-R1beta receptors expressed on the cell surface. Both CRH-R1
      variants were susceptible to homologous desensitization and internalization
      following treatment with CRH; however, PKC activation increased internalization
      of CRH-R1beta but not CRH-R1alpha in a beta-arrestin-independent manner. Our
      findings indicate that CRH-R1alpha and -R1beta exhibit differential responses to
      PKC-induced phosphorylation, and this might represent an important mechanism for
      functional regulation of CRH signaling in target cells.

PMID- 16956984
TI  - A virtual reality apartment as a measure of medication management skills in
      patients with schizophrenia: a pilot study.
AB  - Performance on a novel, virtual reality (VR) assessment of medication management
      skills, the Virtual Reality Apartment Medication Management Assessment (VRAMMA),
      was investigated in 25 patients with schizophrenia and 18 matched healthy
      controls. The VRAMMA is a virtual 4-room apartment consisting of a living room
      with an interactive clock and TV, a bedroom, a kitchen, and a bathroom with an
      interactive medicine cabinet. After an exploratory phase, participants were given
      a mock prescription regimen to be taken 15 minutes later from pill bottles
      located in the medicine cabinet in the bathroom of the virtual environment. The
      VRAMMA was administered with a validated measure of medication management skills,
      several neurocognitive tests, and a symptom scale. Results revealed that (1)
      schizophrenic patients made significantly more quantitative errors in the number
      of pills taken, were less accurate at taking the prescribed medications at the
      designated time, and checked the interactive clock less frequently than healthy
      controls; (2) in patients with schizophrenia, there was significant agreement in
      classification of adherence vs nonadherence between a validated measure of
      medication management skills and the VRAMMA; and (3) in patients with
      schizophrenia, years of education and a measure of verbal learning and memory
      were linked to quantitative errors on the VRAMMA, while positive symptoms,
      specifically delusional symptoms, were inversely linked to distance traveled
      within the VRAMMA. This is the first study, to our knowledge, to provide evidence
      for the utility of VR technology in the assessment of instrumental role
      functioning in patients with schizophrenia.

PMID- 16956985
TI  - Effortful cognitive resource allocation and negative symptom severity in chronic
      schizophrenia.
AB  - BACKGROUND: The relationship between negative symptoms, early visual information
      processing deficits, and effortful processing resource allocation was
      investigated. METHODS: Older patients with chronic schizophrenia (n = 58) and
      healthy controls (n = 71) participated. Pupillary responses were recorded during
      performance of the span of apprehension task (blocks of 3- and 10-letter arrays)
      as an index of resource allocation or mental effort during the task. RESULTS:
      Patients and controls showed larger pupillary responses in higher relative to
      lower processing loads both during array processing and just prior to array onset
      (preparation). Both groups, therefore, invested more cognitive effort preparing
      for and then processing larger arrays. A subgroup of patients with abnormally
      small pupillary responses and impaired performance showed greater negative
      symptom severity relative to a subgroup of patients with normal pupillary
      responses. Smaller pupillary responses in the patients were also significantly
      correlated with greater negative symptom severity, independent of positive
      symptom severity. Patients with reduced effortful resource allocation, therefore,
      exhibited greater negative symptomatology. A subgroup of patients with normal
      pupillary responses still showed impaired detection accuracy relative to
      controls, suggesting that reduced cognitive effort or resource allocation
      problems cannot account for impairments in early visual information processing in
      this subgroup. CONCLUSIONS: The study illustrates important relationships between
      cognitive effort and performance that can impact conclusions about the nature of
      cognitive impairments and associations between negative symptoms and
      neurocognition in schizophrenia.

PMID- 16956986
TI  - Response properties and synchronization of rhythmically firing dendritic neurons.
AB  - The responsiveness of rhythmically firing neurons to synaptic inputs is
      characterized by their phase-response curve (PRC), which relates how weak somatic
      perturbations affect the timing of the next action potential. The shape of the
      somatic PRC is an important determinant of collective network dynamics. Here we
      study theoretically and experimentally the impact of distally located synapses
      and dendritic nonlinearities on the synchronization properties of rhythmically
      firing neurons. By combining the theories of quasi-active cables and phase
      coupled oscillators we derive an approximation for the dendritic responsiveness,
      captured by the neuron's dendritic PRC (dPRC). This closed-form expression
      indicates that the dPRCs are linearly filtered versions of the somatic PRC and
      that the filter characteristics are determined by the passive and active
      properties of the dendrite. The passive properties induce leftward shifts in the
      dPRCs and attenuate them. Our analysis yields a single dimensionless parameter
      that classifies active dendritic conductances as either regenerative conductances
      that counter the passive properties by boosting the dPRCs or restorative
      conductances that high-pass filter the dPRCs. Thus dendritic properties can
      generate a qualitative difference between the somatic and dendritic PRCs. As a
      result collective dynamics can be qualitatively different depending on the
      location of the synapse, the neuronal firing rates, and the dendritic
      nonlinearities. Finally, we use dual whole cell recordings from the soma and
      apical dendrite of cortical pyramidal neurons to test these predictions and find
      that empirical dPRCs are shifted leftward, as predicted, but may also display
      high-pass characteristics resulting from the restorative dendritic HCN (h)
      current.

PMID- 16956987
TI  - Late switch for post-tetanic potentiation: once again it's Ca2+. Focus on "An
      increase in calcium influx contributes to post-tetanic potentiation at the rat
      calyx of Held synapse".

PMID- 16956988
TI  - Activity-dependent modulation of axonal excitability in unmyelinated peripheral
      rat nerve fibers by the 5-HT(3) serotonin receptor.
AB  - Activity-dependent fluctuations in axonal excitability and changes in interspike
      intervals modify the conduction of trains of action potentials in unmyelinated
      peripheral nerve fibers. During inflammation of a nerve trunk, long stretches of
      axons are exposed to inflammatory mediators such as 5-hydroxytryptamine [5-HT].
      In the present study, we have tested the effects of m-chlorophenylbiguanide
      (mCPBG), an agonist at the 5-HT(3) serotonin receptor, on activity- and potential
      dependent variations in membrane threshold and conduction velocity of
      unmyelinated C-fiber axons of isolated rat sural nerve segments. The increase in
      axonal excitability during application of mCPBG was much stronger at higher
      frequencies of action potentials and/or during axonal membrane hyperpolarization.
      The effects on the postspike recovery cycle also depended on the rate of
      stimulation. At an action potential frequency of 1 Hz or in hyperpolarized axons,
      mCPBG produced a loss of superexcitability. In contrast, at 0.33 Hz, a small
      increase in the postspike subexcitability was observed. Similar effects on
      excitability changes were found when latency instead of threshold was recorded,
      but only at higher action potential frequencies: at 1.8 Hz, mCPBG increased
      conduction velocity and reduced postspike supernormality. The latter effect would
      increase the interspike interval if pairs of action potentials were conducted
      along several cm in an inflamed nerve trunk. These data indicate that activation
      of axonal 5-HT(3) receptors not only enhances membrane excitability but also
      modulates action potential trains in unmyelinated, including nociceptive, nerve
      fibers at high impulse rates.

PMID- 16956989
TI  - Load signals assist the generation of movement-dependent reflex reversal in the
      femur-tibia joint of stick insects.
AB  - Reinforcement of movement is an important mechanism by which sensory feedback
      contributes to motor control for walking. We investigate how sensory signals from
      movement and load sensors interact in controlling the motor output of the stick
      insect femur-tibia (FT) joint. In stick insects, flexion signals from the femoral
      chordotonal organ (fCO) at the FT joint and load signals from the femoral
      campaniform sensilla (fCS) are known to individually reinforce stance-phase motor
      output of the FT joint by promoting flexor and inhibiting extensor motoneuron
      activity. We quantitatively compared the time course of inactivation in extensor
      tibiae motoneurons in response to selective stimulation of fCS and fCO.
      Stimulation of either sensor generates extensor activity in a qualitatively
      similar manner but with a significantly different time course and frequency of
      occurrence. Inactivation of extensor motoneurons arising from fCS stimulation was
      more reliable but more than threefold slower compared with the extensor
      inactivation in response to flexion signals from the fCO. In contrast,
      simultaneous stimulation of both sense organs produced inactivation in
      motoneurons with a time course typical for fCO stimulation alone, but with a
      frequency of occurrence characteristic for fCS stimulation. This increase in
      probability of occurrence was also accompanied by a delayed reactivation of the
      extensor motoneurons. Our results indicate for the first time that load signals
      from the leg affect the processing of movement-related feedback in controlling
      motor output.

PMID- 16956990
TI  - Intracortical circuits in rat anterior cingulate cortex are activated by
      nociceptive inputs mediated by medial thalamus.
AB  - We investigated the afferents and intracortical synaptic organization of the
      anterior cingulate cortex (ACC) during noxious electrical stimulation.
      Extracellular field potentials were recorded simultaneously from 16 electrodes
      spanning all layers of the ACC in male Sprague-Dawley rats anesthetized by
      halothane inhalation. Laminar-specific transmembrane currents were calculated
      with the current source density analysis method. Two major groups of evoked sink
      currents were identified: an early group (latency = 54.04 +/- 2.12 ms; 0.63 +/-
      0.07 mV/mm(2)) in layers V-VI and a more intense late group (latency = 80.07 +/-
      4.85 ms; 2.16 +/- 0.22 mV/mm(2)) in layer II/III and layer V. Multiunit
      activities were evoked mainly in layer V and deep layer II/III with latencies
      similar to that of the early and late sink groups. The evoked EPSP latencies of
      pyramidal neurons in layers II/III and V related closely with the sink currents.
      The sink currents were inhibited by intracortical injection of CNQX (1 mM, 1
      microl), a glutaminergic receptor antagonist, and enhanced by intraperitoneal (5
      mg/kg) and intracortical (10 microg/microl, 1 microl) injection of morphine, a mu
      opioid receptor agonist. Paired-pulse depression was observed with interpulse
      intervals of 50 to 1,000 ms. High-frequency stimulation (100 Hz, 11 pulses)
      enhanced evoked responses in the ACC and evoked medial thalamic (MT) unit
      activities. MT lesions blocked evoked responses in the ACC. Our results
      demonstrated that two distinct synaptic circuits in the ACC were activated by
      noxious stimuli and that the MT is the major thalamic relay that transmits
      nociceptive information to the ACC.

PMID- 16956991
TI  - Monoaminergic control of cauda-equina-evoked locomotion in the neonatal mouse
      spinal cord.
AB  - Monoaminergic projections are among the first supraspinal inputs to innervate
      spinal networks. Little is known regarding the role of monoamines in modulating
      ongoing locomotor patterns evoked by endogenous release of neurotransmitter. Here
      we activate a locomotor-like rhythm by electrical stimulation of afferents and
      then test the modulatory effects of monoamines on the frequency, pattern, and
      quality of the rhythm. Stimulation of the cauda equina induced a rhythm
      consisting of left-right and ipsilateral alternation indicative of locomotor-like
      activity. First, we examined the effects of noradrenaline (NA), serotonin (5-HT),
      or dopamine (DA) at dose levels that did not elicit locomotor activity. Bath
      application of NA and DA resulted in a depression of the cauda-equina-evoked
      rhythm. Conversely, bath-applied 5-HT increased both the amplitude and cycle
      period of the evoked rhythm, an effect that was mimicked by the addition of 5
      HT(2) agonists to the bath. Application of 5-HT(7) agonists disrupted the evoked
      rhythmic behavior. Next, we examined the effects of NA alpha(1) and alpha(2)
      agonists and found that the suppressive effects of NA on the rhythm could be
      reproduced by adding the alpha(2) agonist, clonidine, to the bath. In contrast,
      bath applying the alpha(1) agonist, phenylephrine, increased the amplitude and
      duration of the cycle period. Finally, the suppressive effects of DA were not
      replicated by the administration of D(1), D(2), or D(3) agonists although
      application of NA alpha(2) antagonists reversed the effects of DA. Application of
      D(1) agonists, increased the amplitude of the bursts but did not affect the cycle
      period. Our results indicate that monoamines can control the expression, pattern,
      and timing of cauda-equina-evoked locomotor patterns in developing mice.

PMID- 16956992
TI  - Excitatory and inhibitory actions of isoflurane in bovine chromaffin cells.
AB  - Isoflurane, a halogenated volatile anesthetic, is thought to produce anesthesia
      by depressing CNS function. Many anesthetics, including isoflurane, are thought
      to modulate and/or directly activate GABA(A) receptors. Chromaffin cells are
      known to express functional GABA(A) receptors. We previously showed that
      activation of the GABA(A) receptors, with specific agonists, leads to cellular
      excitation resulting from the depolarized anion equilibrium potential. In this
      study, our goal was to determine whether isoflurane mimicked this response and to
      explore the functional consequences of this activation. Furthermore, we sought to
      study the actions of isoflurane on nicotinic acetylcholine receptors (nAChRs) as
      they mediate the "sympathetic drive" in these cells. For these studies the Ca(2+)
      indicator dye fura-2 was used to assay [Ca(2+)](i). Amperometric measurements
      were used to assay catecholamine release. We show that bovine adrenal chromaffin
      cells were excited by isoflurane at clinically relevant concentrations.
      Isoflurane directly activated GABA(A) receptors found in chromaffin cells, which
      depolarized the cells and elevated [Ca(2+)](i). Application of isoflurane
      directly to the chromaffin cells elicited catecholamine secretion from these
      cells. At the same time, isoflurane suppressed activation of nAChRs, which
      presumably blocks "sympathetic drive" to the chromaffin cells. These latter
      results may help explain why isoflurane produces the hypotension observed
      clinically.

PMID- 16956993
TI  - Noisy inputs and the induction of on-off switching behavior in a neuronal
      pacemaker.
AB  - Neuronal oscillators can function as bistable toggle switches, flipping between
      quiescence and rhythmic firing in response to an input stimulus. In theory, such
      switching should be sensitive to small noisy inputs if the bistable states are in
      close proximity, which we test here using a perfused squid axon preparation. We
      find that small noisy stimulus currents induce a multitude of paths between two
      nearby stable states: repetitive firing and quiescence. The pattern of on-off
      switching of the pacemaker depends on the intensity, spectral properties, and
      phase angle of stimulus current fluctuations. Analysis by spike-triggered
      averaging of the stimulus currents near the transitions reveals that sinusoidal
      stimuli timed antiphase or in phase with repetitive firing correlates with
      switching of the pacemaker off or on, respectively. Our results reveal a distinct
      form of bistability in which noise can either silence pacemaker activity, trigger
      repetitive firing, or induce sporadic burst patterns similar to those recorded in
      a variety of normal and pathological neurons.

PMID- 16956994
TI  - Preparatory gain modulation of visuomotor transmission for smooth pursuit eye
      movements in monkeys.
AB  - It has been reported that the visuomotor processing underlying the initiation of
      smooth pursuit eye movement is modulated in relation to the recent experience of
      eye movements: the initial pursuit eye velocity is larger after experiencing
      repeated pursuits than saccades. To assess which parameters of the previously
      executed pursuits play an essential role in modulating the gain of visuomotor
      transmission, we recorded the ocular responses of monkeys to a brief perturbing
      motion of the tracking target injected before the start of the eye movements.
      First, we compared the perturbation responses among the blocks in which the
      duration of executing pursuit was varied. We found that the response amplitude
      increased with the increase of the pursuit duration and it reached a plateau
      level at 100-200 ms of the duration. Second, a comparison of the perturbation
      responses in the blocks in which target velocity was different showed a gradual
      increase of the response as a function of the required pursuit velocity. Third,
      when the animals repeatedly performed pursuits, the response amplitude gradually
      increased with increasing interval between the appearance of the target and the
      onset of perturbation. On the other hand, such an increase was not observed when
      the animals repeatedly performed saccades. These results suggest that before
      initiating eye movements, the pursuit system modulates the gain of visuomotor
      transmission so as to be closely related to the properties of the repeatedly
      experienced eye movements and this gain modulation is triggered by the target's
      appearance.

PMID- 16956996
TI  - Stimulus-dependent alterations in quantal neurotransmitter release.
AB  - Neurotransmitter release is a steep function of the intracellular calcium ion
      concentration ([Ca(2+)](i)) at the release sites. Both the Ca(2+) amplitude and
      the time course appear to be important for specifying neurotransmitter release.
      Ca(2+) influx regulates the number of vesicles exocytosed as well as the amount
      of neurotransmitter each individual vesicle releases. In our study we stimulated
      mouse chromaffin cells in two different ways to alter Ca(2+) presentation at the
      release sites. One method, digitonin permeabilization followed by exposure to
      Ca(2+), allows for a large uniform global elevation of [Ca(2+)](i), whereas the
      second method, application of nicotine, depolarizes chromaffin cells and
      activates voltage-dependent Ca(2+) channels, thereby producing more phasic and
      localized changes in [Ca(2+)](i). Using amperometry to monitor catecholamine
      release, we show that both kinds of stimuli elicit the exocytosis of similar
      quantities of neurotransmitter per large dense core vesicles (LDCVs) released.
      Even so, the release process was quite different for each stimulus; nicotine
      elicited events were small and slow, whereas digitonin events were, in
      comparison, large and fast. In addition, the transient opening of the fusion
      pore, called the "foot," was essentially absent in digitonin-stimulated cells,
      but was quite common in nicotine-stimulated cells. Thus even though both strong
      stimuli used in this study elicited the release of many vesicles it appears that
      the differences in the Ca(2+) levels at the release sites were key determinants
      for the fusion and release of individual vesicles.

PMID- 16956995
TI  - Ethanol inhibition of m-current and ethanol-induced direct excitation of ventral
      tegmental area dopamine neurons.
AB  - Ethanol-induced excitation of ventral tegmental area dopamine (DA VTA) neurons is
      thought to be critical for the reinforcing effects of ethanol. Although ligand
      gated ion channels are known to be the targets of ethanol, ethanol modulation of
      voltage-dependent ion channels of central neurons has not been well studied. We
      have demonstrated that ethanol excites DA VTA neurons by the reduction of
      sustained K(+) currents and recently reported that M-current (I(M)) regulates
      action potential generation through fast and slow afterhyperpolarization phases.
      In the present study we thus examined whether ethanol inhibition of I(M)
      contributes to the excitation of DA VTA neurons using nystatin-perforated patch
      current- and voltage-clamp recordings. Ethanol (20-120 mM) reduced I(M) in a
      concentration-dependent manner and increased the spontaneous firing frequency of
      DA VTA neurons. Ethanol-induced increase in spontaneous firing frequency
      correlated positively with ethanol inhibition of I(M) with a slope value of 1.3.
      Specific I(M) inhibition by XE991 (0.3-10 microM) increased spontaneous firing
      frequency which correlated positively with I(M) inhibition with a slope value of
      0.5. In the presence of 10 muM XE991, a concentration that produced maximal
      inhibition of I(M), ethanol still increased the spontaneous firing frequency of
      DA VTA neurons in a concentration-dependent manner. Thus we conclude that,
      although ethanol causes inhibition of I(M) and this results in some increase in
      the firing frequency of DA VTA neurons, another effect of ethanol is primarily
      responsible for the ethanol-induced increase in firing rate in these neurons.

PMID- 16956997
TI  - Quality assessment and analysis of Biogen Idec compound library.
AB  - A subset of the compound repository for lead identification at Biogen Idec was
      characterized for its chemical stability over a 3-year period. Compounds were
      stored at 4 degrees C as 10 mM DMSO stocks, and a small subset of compounds was
      stored as lyophilized dry films. Compound integrity of 470 discrete compounds
      (Compound Set I) and 1917 combinatorial chemistry-derived compounds (Compound Set
      II) was evaluated by liquid chromatography/mass spectrometry from the time of
      acquisition into the library collection and after 3 years of storage. Loss of
      compound integrity over the 3 years of storage was observed across the 2 subsets
      tested. Of Compound Set I, 63% of samples retained > 80% purity, whereas 57% of
      samples from Compound Set II had purity greater than 60%. The stability of the
      lyophilized samples was superior to the samples stored as DMSO solution. Although
      storage at 4 degrees C as DMSO solution was adequate for the majority of
      compounds, the authors observed and quantified the level of degradation within
      the compound collection. Their study provides general insight into compound
      storage and selection of library subsets for future lead identification
      activities.

PMID- 16956998
TI  - Kinase drug discovery by affinity selection/mass spectrometry (ASMS): application
      to DNA damage checkpoint kinase Chk1.
AB  - Kinase enzymes are involved in a vast array of biological processes associated
      with human disease; therefore, selective kinase inhibition by small molecules and
      therapeutic antibodies is an area of intense study. The authors show that drug
      candidates with immediate value for biological preclinical evaluation can be
      identified directly through ultra-efficient affinity screening of kinase enzymes
      and random compound mixtures. The screening process comprises sampling and
      trapping equilibrium binding between candidate ligands and protein in solution,
      followed by removal of unbound ligands via 3 rounds of ultrafiltration and direct
      identification of bound ligands by mass spectrometry. Evaluation of significant
      peaks is facilitated by automated integration and collation of the mass spectral
      data and import into custom software for analysis. One Chk1-selective ligand
      found by using this process is presented in detail. The compound is potent in
      both enzymatic and Chk1-dependent cellular assays, and specific contacts in the
      Chk1 active site are shown by X-ray crystallography.

PMID- 16956999
TI  - "Kiss-and-run" exocytosis in astrocytes.
AB  - Neurons and glia are the principal cellular components of the nervous system.
      Although the glia are 10 times more numerous than neurons, until recently they
      were thought to be passive cells that monitor and support the active neurons by
      taking up used neurotransmitters from the synapses. In the past few years, this
      concept has been challenged by the findings that Ca(2+) waves spread from one
      astrocyte to another via Ca(2+)-and SNARE (soluble N-ethylmaleimide-sensitive
      factor attachment protein receptor)-dependent gliotransmitter release in pure
      cultures of astrocytes, raising the possibility that glia are not so passive as
      previously thought. This hypothesis was further advanced by two recent reports,
      which demonstrated that astrocytes release glutamate via vesicular exocytosis in
      response to stimuli. The kinetics of single vesicle exocytosis is distinct from
      its neural equivalent, because in response to physiological stimulation,
      gliotransmitter release is exclusively in the mode of "kiss and run." These
      advances were made possible by newly available techniques for single vesicle
      recordings, which will also be briefly reviewed here.

PMID- 16957000
TI  - Spinal and brain control of human walking: implications for retraining of
      walking.
AB  - In this update, the authors will discuss evidence for both spinal and brain
      regulation of walking in humans. They will consider the sensory control of
      walking in young babies and spinal cord-injured adults, two models with weak
      descending input from the brain, to suggest that subcortical structures are
      important in shaping walking behavior. Based on evidence from development, the
      authors suggest that the primitive pattern of walking seen in babies forms the
      base upon which additional features are added by supraspinal input as independent
      walking develops. Increasing evidence suggests the motor cortex is important in
      the control of level-ground walking in adults, in contrast to quadrupeds. This
      brain input seems particularly important for distal flexors in the leg. Finally,
      the authors will consider evidence that the recovery of walking after incomplete
      spinal cord injuries is dependent on the presence of descending input from the
      motor cortex and our ability to strengthen that input. These findings imply that
      training methods for improving walking after injury to the nervous system must
      promote the involvement of both spinal and brain circuits.

PMID- 16957001
TI  - The paradigm of complexity in clinical neurocognitive science.
AB  - Neurocognitive science represents the modern approach to integrating the
      subdisciplines aimed at a scientific study of the brain-mind system. This
      relatively new discipline recognizes, implicitly or explicitly, that this is a
      complex system whose states and processes are determined by multiple bio-psycho
      social variables and order parameters. In a generic perspective, all
      neurocognitive science is complex, as it is multidisciplinary, but in some
      studies, complexity has become a more defined scientific paradigm using its own
      specific empirical and theoretical tools. Some neuroscientists consider
      complexity science as a specific and formalized paradigm. Between their
      contributions, the author will try to highlight some current promising paths and
      new frontiers for neuroscience. In this perspective, he will mostly focus on
      those contributions directly related to clinical perspectives. This is the reason
      why some seminal contributions more focused on physiological functioning might
      not be mentioned.

PMID- 16957002
TI  - Axon pruning and synaptic development: how are they per-plexin?
AB  - During the development of the nervous system, neurons must first migrate to their
      appropriate locations and then send out axons to make connections. Various
      environmental cues guide these migrating neurons and growing axons. After axons
      reach their target regions, neuronal contacts are created through the formation
      of synapses. Because excess axonal branches and synaptic contacts are often
      formed during early development, they are pruned or eliminated at later stages to
      create specific neuronal connections. Several groups of ligand-receptor pairs
      have been identified to regulate each of these cellular events. Evidence also
      indicates that these same molecules may be used in multiple developmental
      processes. Here, we discuss semaphorins and plexins, the largest family of axon
      guidance ligand-receptor pairs. Because the roles of semaphorins in neuronal
      migration and axonal repulsion have been extensively reviewed, we will focus on
      plexin receptors. We will discuss how semaphorin signals are specifically passed
      through these receptors into cells and how plexins mediate their newly identified
      roles in axon pruning and synaptic development.

PMID- 16957003
TI  - Sleep to remember.
AB  - Recently, compelling evidence has accumulated that links sleep to learning and
      memory. Sleep has been identified as a state that optimizes the consolidation of
      newly acquired information in memory. Consolidation is an active process that is
      presumed to rely on the covert reactivation and reorganization of newly encoded
      representations. Hippocampus-dependent memories benefit primarily from slow-wave
      sleep (SWS), whereas memories not depending on the hippocampus show greater gains
      over periods containing high amounts of rapid eye movement sleep. One way sleep
      does this is by establishing different patterns of neurotransmitters and
      neurohormone secretion between sleep stages. Another central role for
      consolidating memories is played by the slow oscillation, that is, the
      oscillating field potential change dominating SWS. The emergence of slow
      oscillations in neocortical networks depends on the prior use of these networks
      for encoding of information. Via efferent pathways, they synchronize the
      occurrence of sharp wave ripples accompanying memory reactivations in the
      hippocampus with thalamocortical spindle activity. Thus, hippocampal memories are
      fed back into neocortical networks at a time when these networks are depolarized
      and, because of concurrent spindle activity, can most sensitively react to these
      inputs with plastic changes underlying the formation of long-term memory
      representations.

PMID- 16957004
TI  - Lipid signaling and synaptic plasticity.
AB  - Lipids are essential components of plasma- and organelle-membranes, not only
      providing a frame for embedded proteins (e.g., receptors and ion channels) but
      also functioning as reservoirs for lipid mediators. Increasing evidence indicates
      that bioactive lipids such as eicosanoids, endocannabinoids, and
      lysophospholipids serve as intercellular and intracellular signaling molecules
      participating in physiological and pathological functions in the brain. The
      discovery of some of these lipid receptors and novel lipid signaling mediators
      has sparked an intense interest in lipidomic neurobiology research. Classic
      prostaglandins (PGD(2), PGE(2), PGF(2alpha), PGI(2), and TXA(2)), catalyzed by
      cyclooxygenases (COX), are synthesized from arachidonic acid (AA). Experimental
      studies demonstrate that prostaglandin E(2) (PGE(2)), mainly derived from the COX
      2 reaction, is an important mediator, acting as a retrograde messenger via a
      presynaptic PGE(2) subtype 2 receptor (EP(2)) in modulation of synaptic events.
      Novel prostaglandins (prostaglandin glycerol esters and prostaglandin
      ethanolamides) are COX-2 oxidative metabolites of endogenous cannabinoids (2
      arachidonyl glycerol and arachidonyl ethanolamide). Recent evidence suggests that
      these new types of prostaglandins are likely novel signaling mediators involved
      in synaptic transmission and plasticity. This means that COX- 2 plays a central
      role in metabolisms of AA and endocannabinoids (eCBs) and productions of AA- and
      eCB- derived prostaglandins. Thus, in the present review article, the authors
      will mainly discuss COX-2 regulation of prostaglandin signaling in modulation of
      hippocampal synaptic transmission and plasticity.

PMID- 16957005
TI  - Neuropathological and genetic findings in autism: the significance of a putative
      minicolumnopathy.
AB  - Autism is a condition manifested as abnormalities of relatedness, communication,
      range of interests, and repetitive behaviors. Despite alarming prevalence
      estimates and exhortations to research, little is known regarding its
      pathophysiology. Recent reports of a putative minicolumnopathy explain changes in
      brain size, gray/white matter ratios, and interareal connectivity. This article
      summarizes possible links between minicolumns and other topics-cortical
      modularity, age of onset, gliosis, and genetics-relevant to the pathophysiology
      of autism.

PMID- 16957006
TI  - The rhythmic consequences of ion channel stochasticity.
AB  - Ion channels are membrane-spanning proteins with central pores through which ions
      cross neuronal membranes. The pores through each ion channel flicker between open
      and closed states, starting and stopping the flow of ions and the electrical
      current they carry. Hence the current flickers on and off, varying widely on very
      short time scales. Recent evidence suggests that this noisy current is a source
      of rhythmic behaviors in neurons. In this review, we begin by providing an
      illustrative model that links the stochastic flicker of ion channels to neuronal
      rhythms. The author explores recent experimental work that shows channel flicker
      is necessary for at least one rhythm that characterizes a class of cortical
      neurons in vitro. Finally, the author highlights a number of novel studies that
      link ion channel stochasticity to neuronal rhythmic behaviors in other
      interesting ways.

PMID- 16957007
TI  - Isolated posterior labrum tear in a golfer: a case report.

PMID- 16957009
TI  - The morbidity associated with osteochondral harvest from asymptomatic knees for
      the treatment of osteochondral lesions of the talus.
AB  - BACKGROUND: Mosaic autogenous osteochondral transplantation has been used to
      treat large osteochondral defects. HYPOTHESIS: There is potential, previously
      unrecognized donor-site morbidity associated with osteochondral harvest from
      asymptomatic knees for the treatment of talar osteochondral defect lesions. STUDY
      DESIGN: Case series; Level of evidence, 4. METHODS: Fifteen patients underwent
      mosaic osteochondral transplantation to treat a talar osteochondral defect
      lesion, with 11 patients available for follow-up. A Lysholm knee score was used
      to assess donor-site morbidity at a mean follow-up of 47 months (range, 7-77
      months). Mean age was 29 years (range, 21-44 years). A single surgical team
      performed the mosaicplasties. Significance was determined using the Student t
      test. RESULTS: All patients had asymptomatic knees preoperatively. Mean
      postoperative Lysholm score was 81 (range, 49-100). By Lysholm criteria, 5 rated
      as excellent, 2 as good, and 4 as poor. No significant difference was detected in
      terms of the harvest method or the number of grafts obtained from those having an
      excellent rating versus those having a good/poor rating. Patients rated as
      good/poor cited knee instability in daily activities as the most common problem.
      One had knee pain and patellar instability after osteochondral harvest by lateral
      arthrotomy that required a subsequent lateral retinacular release and tibial
      tubercle osteotomy. CONCLUSION: This study demonstrates that donor-site morbidity
      after osteochondral harvest can be significant. In this population, those who
      experienced a decline in knee function had problems performing activities of
      daily living. When performing these procedures, the authors recommend that
      surgeons consider these risks and discuss them with their patients.

PMID- 16957008
TI  - Hydrogel meniscal replacement in the sheep knee: preliminary evaluation of
      chondroprotective effects.
AB  - BACKGROUND: Meniscal allograft transplantation has become a viable surgical
      alternative for a select group of patients with deficient or irreparable menisci.
      Subjective results are encouraging; long-term success, durability, and safety of
      allograft meniscal transplantation are uncertain. PURPOSES: To evaluate a novel
      hydrogel meniscal replacement implant in an ovine model and assess
      chondroprotective effects of this hydrogel meniscal replacement using several
      validated outcome measures. STUDY DESIGN: Controlled laboratory study. METHODS:
      Fourteen skeletally mature sheep underwent hydrogel meniscal replacement; 45
      additional animals had previously undergone 1 of 3 operations: lateral
      meniscectomy (24), meniscal allograft transplant (17), and sham (4). Animals were
      sacrificed at 2, 4, or 12 months. Cartilage was assessed by magnetic resonance
      imaging, gross inspection, biomechanical testing, and semiquantitative
      histological analysis. RESULTS: There were no differences between the sham
      operation and nonoperated control limbs. Compared with meniscectomy, hydrogel
      meniscal replacement resulted in significantly decreased cartilage degeneration
      with all outcome parameters (P < .05). Compared with nonoperated control limbs,
      hydrogel meniscal replacements demonstrated no significant differences at 2
      months in any category. By 4 months, hydrogel limbs demonstrated significantly
      greater cartilage degeneration than did nonoperated control limbs in all
      categories. Compared with meniscal allograft transplantation animals, hydrogel
      meniscal replacements demonstrated no differences at 2 months but had
      significantly increased cartilage degeneration in the peripheral zone of the
      tibial plateau at 4 months (P < .05). At 1 year, all hydrogel implants had
      developed complete radial splits in the posterior third of the implant.
      CONCLUSION: Although promising preliminary results for hydrogel meniscal
      replacement were seen at early time points, significant cartilage degeneration
      and implant failure were seen at 1 year, and overall performance was worse than
      was allograft transplantation. Improvements in hydrogel material properties and
      surface characteristics and more accurate size matching may improve outcomes.
      CLINICAL RELEVANCE: Improvements in the hydrogel material properties and surface
      characteristics and more accurate size matching may lead to the use of hydrogel
      implants in humans.

PMID- 16957010
TI  - Longitudinal validation of a modified Edmonton symptom assessment system (ESAS)
      in haemodialysis patients.
AB  - BACKGROUND: Health-related quality of life (HRQL) is an important outcome in the
      treatment of end-stage renal disease (ESRD) and appears to be highly associated
      with patient self-report of symptom burden. This study examines the longitudinal
      validity of the modified Edmonton symptom assessment system (ESAS) to determine
      the impact of change in symptom burden on the change in HRQL of haemodialysis
      (HD) patients. METHODS: 261 haemodialysis patients completed the Kidney Disease
      Quality of Life-Short Form (KDQOL-SF) and the ESAS at baseline and at 6 months.
      RESULTS: The change in overall symptom distress score was strongly correlated
      with the change in KDQOL-SF subscales symptom/problem list (R=-0.73, P<0.01),
      effects of kidney disease (R=-0.53, P<0.01), and burden of kidney disease (R=
      0.46, P<0.01) as well as overall physical health composite (R=-0.58, P<0.01) and
      overall mental health composite (R=-0.68, P<0.01). The change in symptom burden,
      as described by the ESAS, accounted for 46% of the change in the mental HRQL and
      34% of the change in the physical HRQL. There was no correlation between baseline
      demographics, comorbidity or changes in biochemical markers with changes in
      either the ESAS or HRQL scores. CONCLUSION: The modified ESAS is a simple, valid
      tool for the longitudinal assessment of physical and psychological symptom burden
      in ESRD and is responsive to change in HD patients. The use of this symptom
      assessment scale and improved management of patient symptoms would be expected to
      positively impact HD patients' HRQL.

PMID- 16957011
TI  - Apoptotic stress pathway activation mediated by iron on endothelial cells in
      vitro.
AB  - BACKGROUND: Iron sucrose (Fe-S) and low-molecular-weight iron dextran (Fe-D) have
      been used successfully in the treatment of anaemia in chronic kidney disease
      patients. However, some side effects, such as endothelial cell dysfunction have
      been reported. Mechanisms by which iron can induce endothelial cell damage have
      not been completely understood. This study was designed to examine the effect of
      Fe-S and Fe-D on bovine aortic endothelial cells in vitro. METHODS: Cell
      proliferation was determined by [3H] thymidine incorporation, cytotoxicity by
      lactate dehydrogenase, pro-Caspase-3 by immunoblotting; and Caspase-3 activity
      using a colorimetric assay. Expression of the apoptosis stress pathway proteins
      Bcl-2 and Bax and cycle arrest proteins p53 and p21WAF/CIP1 were examined by
      immunoblot. Cell apoptosis was tested by terminal deoxynucleotidyltransferase
      mediated nick-end labelling (TUNEL) and DNA fragmentation. RESULTS: Both iron
      preparations inhibited cell proliferation. This effect was more important and
      occurred at lower concentrations in Fe-S than Fe-D cultured cells. Expression of
      p53 and p21WAF/CIP1 increased in cells incubated with Fe-S, but not with Fe-D.
      Bcl-2 expression was significantly down-regulated in cells incubated with Fe-S in
      comparison with Fe-D, while Bax expression was not modified by the iron
      compounds. Pro-Caspase-3 expression and Caspase-3 activity increased only in
      cells treated with Fe-S. Apoptosis was present in cells treated with Fe-S.
      CONCLUSIONS: Our results demonstrate that Fe-S exerts a greater inhibitory effect
      on endothelial cell proliferation than Fe-D. The mechanisms involved in this
      process may be related, at least in part, to over expression of proteins related
      to the cell cycle arrest and apoptosis stress pathway.

PMID- 16957013
TI  - Peritoneal dialysis solutions and patient survival: does wishing make it so?

PMID- 16957012
TI  - Changing prescribing practice in CAPD patients in Korea: increased utilization of
      low GDP solutions improves patient outcome.
AB  - BACKGROUND: Novel, biocompatible peritoneal dialysis (PD) solutions have become
      available in recent years. In 2001, low glucose degradation products (GDP),
      neutral pH solutions became commercially available in Korea. To date, there are
      no reports regarding the large scale adoption of these solutions in clinical
      practice and regarding what, if any, impact these solutions have on patient
      outcomes. METHODS: Using a database of almost 4000 patients treated by PD in
      Korea, we conducted a prospective, longitudinal observational study documenting
      the patterns of use of one novel low GDP solution (balance, Fresenius Medical
      Care, St Wendel, Germany) in 1909 PD incident patients between 1 January 2002 and
      midyear 2005. Outcomes including patient and technique survival and peritonitis
      rates were analysed using univariate and multivariate analysis. RESULTS:
      Prescription of low GDP solutions reached between 70 and 80% by the year 2003 and
      persisted at this level. Patients prescribed low GDP PD solution tended to be
      younger and were more likely to be treated in centres with larger enrollment in
      the database. Survival of diabetic patients treated with the new PD solution was
      identical to that of the non-diabetic patients treated with standard PD fluids
      (PDF) and treatment with low GDP PDF independently reduced the relative risk (RR)
      of death (RR = 0.613; CI 0.50-0.74; P < 0.00001) in a proportional hazards model
      which included age, diabetes and centre experience. In a univariate analysis, low
      GDP PD solution was associated with a longer technique survival (P = 0.049) but
      this effect was not significant in multivariate analysis. No significant
      differences in peritonitis-free interval or peritonitis rate could be attributed
      to the prescribed PDF. CONCLUSION: Prescription of low GDP, pH-neutral PD
      solutions has rapidly increased in Korea. This change has resulted in a
      significant improvement in patient and technique survival without any measurable
      change in peritonitis incidence or rate. Reasons for the improved patient
      survival cannot be determined from this analysis and require further study.

PMID- 16957014
TI  - Evaluation of histological techniques for quantifying haemodialysis arteriovenous
      (AV) graft hyperplasia.
AB  - BACKGROUND: Assessing treatment efficacies for preventing haemodialysis
      arteriovenous (AV) graft stenosis requires a reproducible method for quantifying
      intimal hyperplasia. We identified sources of variability in three histological
      methods for assessing hyperplasia in a porcine AV graft model. METHODS: Carotid
      jugular synthetic grafts were placed in pigs. After explantation at 3-6 weeks,
      the tissue was stained with haematoxylin and eosin (H&E), Masson's trichrome or
      elastic tissue Van Gieson (EVG) stains and examined histologically. Hyperplasia
      at the anastomosis of 14 grafts was quantified using three different methods,
      each by four blinded observers. These methods were visual scoring, ratio of
      intima-to-media surface area (I/M ratio), and ratio of intra-graft hyperplasia to
      graft surface area (H/G ratio) at the graft-vessel interface. RESULTS: The EVG
      stain proved superior in delineation of the elastic lamina yet quantification of
      the intimal and medial layers was still often difficult. This is illustrated by
      the greater inter-observer median coefficient of variances (CV) found using the
      I/M ratio method (intimal area CV=13.7%; medial area CV=32.7%; I/M ratio
      CV=44.0%) than with the H/G method (intra-graft hyperplasia area CV=7.3%, graft
      area CV=5.3%; H/G ratio CV=6.9%) or by visual scoring (CV=26.8%). The H/G ratios
      correlated positively with visual scores (r=0.941; P=0.0007; n=14) and the I/M
      ratio (r=0.719; P=0.0095; n=14). While hyperplasia was seen in both native vessel
      and graft lumen, in only one of the 14 anastomoses was the degree of hyperplasia
      greater in the native vessel than in the graft lumen, suggesting that the degree
      of hyperplasia occurring within the graft lumen predicted the total hyperplasia
      around the anastomosis. CONCLUSIONS: The H/G method for assessing hyperplasia is
      preferred in a porcine model of AV graft because it is quantitative, less
      variable and does not require the delineation of the elastic lamina, although it
      infrequently underestimates the total hyperplasia that occurs.

PMID- 16957015
TI  - Body image and perceived health in adolescence.
AB  - Perceived health is an important health predictor, and self-assessed health
      during adolescence is of great interest. This study examined the relationship
      between perceived negative health and body image in early and mid-adolescence,
      focusing on age and gender differences. Analyses were based on Norwegian data
      from a World Health Organization cross-national survey (Health Behaviour in
      School-Aged Children) among 5026 pupils aged 11, 13 and 15 years. The response
      rate was 76%. Stratified analyses with presentations of frequency and relative
      risk were performed, as well as logistic regression analyses. Girls are more
      likely to report negative health than boys are, and the probability of such
      reports increases with age. Girls and older age groups report dieting and
      dissatisfaction with weight and appearance more often than boys and younger age
      groups. Body dissatisfaction is associated with an increased risk of perceived
      negative health, also when controlling for the possible confounding effects of
      age and gender. The present 'ideals' of weight and appearance might contribute to
      an unfavourable perception of health in this age group.

PMID- 16957016
TI  - Respiratory potential and Se compounds in pea (Pisum sativum L.) plants grown
      from Se-enriched seeds.
AB  - Selenium (Se) has been proved to be an essential element for humans and animals.
      However, less is known about its effects on plants. Pea plants were treated
      foliarly once (OT) and twice (TT) with Se solution during their flowering period.
      Seeds obtained from these plants contained 383 and 743 ng Se g(-1), respectively,
      and, together with control seeds from untreated plants (UT) containing 21 ng Se
      g(-1), were sown in soil in a greenhouse. Se content and its chemical form in
      young plants were studied, and its impact on plant respiratory potential,
      measured as terminal electron transport system (ETS) activity, determined. ETS
      activity was highest in young pea leaves with the highest Se content. Higher ETS
      activity possibly reflected increased glutathione peroxidase (GSH-Px) activity in
      mitochondria. The Se content of leaves and stems of plants grown from control
      seeds was similar to that in the seed, being around 40 ng Se g(-1). Se
      concentration in leaves of young plants grown from OT and TT seeds was 605%, and
      1340% higher, respectively, than the control, and in their stems 355%, and 680%
      higher, respectively. The ratio of Se concentrations in OT and TT seeds was the
      same as in the leaves and stems in the young plants grown from them. SeMet was
      the major Se compound in Se-rich pea seeds and leaves, comprising 49% and 67% of
      the total Se content in OT and TT seeds, respectively, and 85% and 79% in the
      corresponding leaves.

PMID- 16957017
TI  - The gene encoding the cytosolic small subunit of ADP-glucose pyrophosphorylase in
      barley endosperm also encodes the major plastidial small subunit in the leaves.
AB  - The barley (Hordeum vulgare) gene Hv.AGP.S.1 produces two different transcripts
      encoding small subunits (SSUs) of ADP-glucose pyrophosphorylase (AGPase). It was
      shown previously that one of these transcripts, Hv.1a, encodes the cytosolic SSU
      in the endosperm. It is shown here that the other transcript produced from
      Hv.AGP.S.1, Hv.1b, encodes a plastidial SSU that is required for >90% of the
      AGPase activity in the leaves. Thus, both of the alternative transcripts encoded
      by Hv.AGP.S.1 are physiologically relevant: One is important for starch synthesis
      in the endosperm and the other for starch synthesis in the leaves. Although the
      Hv.1b transcript is abundant in embryos and present in endosperm, there is no
      evidence that a protein is produced from this transcript in these organs. This
      suggests that some, as yet unidentified, post-transcriptional control mechanism
      prevents the accumulation of the protein encoded by Hv.1b in embryos and
      endosperm but not in leaves. There is one other known gene in barley, Hv.AGP.S.2,
      encoding a SSU of AGPase. This gene has been shown to be responsible for the
      plastidial SSU in the endosperm. It is shown here that Hv.AGP.S.2 probably also
      makes some contribution to the SSU of AGPase in the leaves and may be responsible
      for most or all of the plastidial SSU in a range of non-photosynthetic plant
      organs including the embryo.

PMID- 16957019
TI  - DNA degradation and nuclear degeneration during programmed cell death in petals
      of Antirrhinum, Argyranthemum, and Petunia.
AB  - Programmed cell death (PCD) was studied in the petals of Antirrhinum majus,
      Argyranthemum frutescens, and Petunia hybrida, using DNA degradation and changes
      in nuclear morphology as parameters. The petals exhibit loss of turgor (wilting)
      as a visible symptom of PCD. DNA degradation, as shown on agarose gels, occurred
      in all species studied, prior to visible wilting. The number of DNA masses in all
      the petals of a flower, determined by flow cytometry, markedly increased in
      Argyranthemum and Petunia, but decreased in Antirrhinum. Many small DNA masses
      were observed in Argyranthemum and Petunia. The surface of each small DNA mass
      stained with the lipophilic fluorochrome 3,3'-dihexyloxacarbocyanine iodide
      (DiOC6), indicating that these masses were surrounded by a membrane. In
      Antirrhinum, in contrast, the chromatin fragmented into several small spherical
      clumps that remained inside a large membranous structure. Nuclear fragmentation,
      therefore, did not occur in Antirrhinum, whereas nuclear fragmentation possibly
      was a cause of the small DNA masses in Argyranthemum and Petunia. It is concluded
      that at least two contrasting nuclear morphologies exist during PCD. In the
      first, the chromatin fragments inside the nucleus, not accompanied--or followed-
      by nuclear fragmentation. In the second, a large number of DNA masses were
      observed each enveloped by a membrane. The second type was probably due, at least
      partially, to nuclear fragmentation.

PMID- 16957018
TI  - Expression of BjMT2, a metallothionein 2 from Brassica juncea, increases copper
      and cadmium tolerance in Escherichia coli and Arabidopsis thaliana, but inhibits
      root elongation in Arabidopsis thaliana seedlings.
AB  - The protective function of a plant type-2 metallothionein was analysed after
      expression in Escherichia coli and in Arabidopsis thaliana seedlings. BjMT2 from
      Brassica juncea was expressed in E. coli as a TrxABjMT2 fusion protein. After
      affinity chromatography and cleavage from the TrxA domain, pure BjMT2 protein was
      obtained which strongly reacted with the thiol reagent monobromobimane.
      Escherichia coli cells expressing the TrxABjMT2 fusion were more tolerant to Cu2+
      and Cd2+ exposure than control strains. Likewise, when BjMT2 cDNA was expressed
      in A. thaliana under the regulation of the 35S promoter, seedlings exhibited an
      increased tolerance against Cu2+ and Cd2+ based on shoot growth and chlorophyll
      content. Analysis of transiently transformed cells of A. thaliana and tobacco
      leaves by confocal laser scanning microscopy (CLSM) revealed exclusive cytosolic
      localization of a BjMT2::EGFP (enhanced green fluorescent protein) fusion protein
      in control and heavy metal-exposed plant cells. Remarkably, ectopic expression of
      BjMT2 reduced root growth in the absence of heavy metal exposure, whereas in the
      presence of 50 or 100 microM Cu2+ root growth in control and transgenic lines was
      identical. The results indicate that in A. thaliana, root and shoot development
      are differentially affected by ectopic expression of BjMT2.

PMID- 16957020
TI  - Ketocarotenoid formation in transgenic potato.
AB  - Potato has been genetically engineered for the production of commercially
      important ketocarotenoids including astaxanthin (3,3'-dihydroxy 4,4'-diketo-beta
      carotene). To support the formation of 3-hydroxylated and 4-ketolated beta
      carotene, a transgenic potato line accumulating zeaxanthin due to inactivated
      zeaxanthin epoxidase was co-transformed with the crtO beta-carotene ketolase gene
      from the cyanobacterium Synechocystis under a constitutive promoter. Plants were
      generated which exhibited expression of this gene, resulting in an accumulation
      of echinenone, 3'-hydroxyechinenone, and 4-ketozeaxanthin in leaves, as well as
      3'-hydroxyechinenone, 4-ketozeaxanthin together with astaxanthin in the tuber.
      The amount of ketocarotenoids formed represent approximately 10-12% of total
      carotenoids in leaves and tubers. Negative effects on photosynthesis due to the
      presence of the ketocarotenoids in leaves could be excluded by the determination
      of variable fluorescence.

PMID- 16957021
TI  - ENOD40 affects elongation growth in tobacco Bright Yellow-2 cells by alteration
      of ethylene biosynthesis kinetics.
AB  - Plant developmental processes are controlled by co-ordinated action of
      phytohormones and plant genes encoding components of developmental response
      pathways. ENOD40 was identified as a candidate for such a plant factor with a
      regulatory role during nodulation. Although its mode of action is poorly
      understood, several lines of evidence suggest interaction with phytohormone
      response pathways. This hypothesis was investigated by analysing cytokinin-,
      auxin-, and ethylene-induced responses on cell growth and cell division in
      transgenic 35S:NtENOD40 Bright Yellow-2 (BY-2) tobacco cell suspensions. It was
      found that cell division frequency is controlled by the balance between cytokinin
      and auxin in wild-type cells and that this regulation is not affected in
      35S:NtENOD40 lines. Elongation growth, on the other hand, is reduced upon
      overexpression of NtENOD40. Analysis of ethylene homeostasis shows that ethylene
      accumulation is accelerated in 35S:NtENOD40 lines. ENOD40 action can be
      counteracted by an ethylene perception blocker, indicating that ethylene is a
      negative regulator of elongation growth in 35S:NtENOD40 cells, and that the
      NtENOD40-induced response is mediated by alteration of ethylene biosynthesis
      kinetics.

PMID- 16957022
TI  - Identification of a stage-specific permissive in vitro culture environment for
      follicle growth and oocyte development.
AB  - The availability of viable oocytes is the limiting factor in the development of
      new reproductive techniques. Many attempts have been made to grow immature
      oocytes in vitro during recent decades. Recently, a modified alginate-based three
      dimensional culture system was designed to support the growth and maturation of
      multilayered secondary follicles. This system was able to produce oocytes that
      successfully completed meiosis, fertilization, and development to the blastocyst
      stage. Subsequent attempts to culture two-layered secondary follicles were
      unsuccessful under the original conditions. Herein, we investigated the effect of
      alginate consistency on two-layered follicle growth and oocyte developmental
      competence by encapsulating follicles into alginate scaffolds of various
      concentrations. Although there were no significant differences in survival rates,
      0.25% and 0.5% alginate supported more rapid growth of follicles and antrum
      formation compared with 1.5% and 1.0% alginate after 8 days of culture. Alginate
      scaffold concentration also affected the proliferation and differentiation of
      somatic cells (theca and granulosa cells), measured in terms of morphological
      changes, steroid profiles (androstenedione, estradiol, and progesterone), and
      specific molecular markers (Fshr, Lhcgr, and Gja1). Theca cell proliferation and
      steroid production were hindered in follicles cultured in 1.5% alginate. In vitro
      fertilization and embryo culture revealed that oocytes obtained from 0.25%
      alginate retained the highest developmental competence. Overall, the present
      study showed that the alginate scaffold consistency affects folliculogenesis and
      oocyte development in vitro and that the alginate culture system can and should
      be tailored to maximally support follicle growth depending on the size and stage
      of the follicles selected for culture.

PMID- 16957023
TI  - Kinetics of the progesterone-induced acrosome reaction and its relation to
      intracellular calcium responses in individual human spermatozoa.
AB  - Progesterone at 3 microM triggers a biphasic (transient and sustained) increase
      in intracellular calcium ([Ca(2+)](i)) in human sperm, which is believed to be a
      prerequisite for progesterone-induced acrosome reaction (AR). As very little is
      known about how AR occurrence, latency, and completion relate to the
      characteristics of the progesterone-induced [Ca(2+)](i) signal, we examined these
      events using fluorescence microscopy of individual living human sperm. Direct
      assessment of acrosomal status after calcium imaging showed no differences in
      kinetics or amplitude of the preceding progesterone-induced calcium responses in
      acrosome-reacted and acrosome-intact cells, which indicates that the amplitude of
      the [Ca(2+)](i) signal is not the critical determinant of AR. Chelation of
      extracellular calcium to arrest AR at varying times after progesterone
      stimulation revealed that maximal AR occurred immediately following progesterone
      stimulation, during the initial transient calcium influx rather than during the
      sustained calcium response. Attempts to follow acrosomal dispersal in real-time
      by staining with the acidic organelle probes LysoTracker DND-99 and dapoxyl (2
      aminoethyl) sulphonamide (DAES) proved inconclusive due to heterogeneous labeling
      of the cell population. Surprisingly, the dye was often not confined to the
      acrosome but stained the whole sperm head, which suggests that only a
      subpopulation of human sperm cells contains a sufficiently acidic acrosome.

PMID- 16957024
TI  - Effects of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 on cytokine
      production by human decidual cells.
AB  - The active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25[OH](2)D(3)) is a
      potent immunomodulatory seco-steroid. We have demonstrated that several
      components of vitamin D metabolism and signaling are strongly expressed in human
      uterine decidua from first trimester pregnancies, suggesting that locally
      produced 1,25(OH)(2)D(3) may exert immunosuppressive effects during early stages
      of gestation. To investigate this further, we used primary cultures of human
      decidual cells from first and third trimester pregnancies to demonstrate
      expression and activity of the enzyme that catalyzes synthesis of
      1,25(OH)(2)D(3), 1alpha-hydroxylase (CYP27B1). Synthesis of 1,25(OH)(2)D(3) was
      higher in first trimester decidual cells (41 +/- 11.8 fmoles/h/mg protein) than
      in third trimester cells (8 +/- 4.4 fmoles/h/mg protein; P < 0.05). Purification
      of decidual cells followed by quantitative RT-PCR analysis showed that CYP27B1
      was expressed by both CD10(+VE) stromal-enriched and CD10(-VE) stromal-depleted
      cells, with higher levels of mRNA in first trimester pregnancies. Expression of
      CYP27B1 correlated with TLR4 and IDO. Functional responses to 1,25(OH)(2)D(3)
      were studied using CD56(+VE) natural killer (NK) cells isolated from first
      trimester decidua. Decidual NK cells treated with 1,25(OH)(2)D(3) or precursor 25
      hydroxyvitamin D(3) (25OHD(3)) for 28 h showed decreased synthesis of cytokines,
      such as granulocyte-macrophage colony stimulating factor 2 (CSF2), tumor necrosis
      factor, and interleukin 6, but increased expression of mRNA for the antimicrobial
      peptide cathelicidin antimicrobial peptide. These data indicate that human
      decidual cells are able to synthesize active 1,25(OH)(2)D(3), particularly in
      early gestation, and this may act in an autocrine/paracrine fashion to regulate
      both acquired and innate immune responses at the fetal-maternal interface.

PMID- 16957025
TI  - Severe feto-placental abnormalities precede the onset of hypertension and
      proteinuria in a mouse model of preeclampsia.
AB  - Preeclampsia is a prevalent and potentially devastating disorder of pregnancy.
      Characterized by a sudden spike in blood pressure and urinary protein levels, it
      is associated with significant obstetric complications. BPH/5 is an inbred mouse
      model of preeclampsia with borderline hypertension before pregnancy. BPH/5 mice
      develop hypertension, proteinuria, and endothelial dysfunction during late
      gestation (after E14.5). We hypothesized that BPH/5 mice might exhibit early feto
      placental abnormalities before the onset of maternal disease. All placental cell
      lineages were present in BPH/5 mice. However, the fetal and placental weights
      were reduced, with abnormalities in all the placental zones observed starting
      early in gestation (E9.5-E12.5). The fractional area occupied by the junctional
      zone was significantly reduced at all gestational timepoints. Markedly fewer
      CDKN1C-stained trophoblasts were seen invading the proximal decidual zone, and
      this was accompanied by reductions in Cdkn1c gene expression. Trophoblast giant
      cell morphology and cytokeratin staining were not altered, although the mRNA
      levels of several giant cell-specific markers were significantly downregulated.
      The labyrinth layer displayed decreased branching morphogenesis of endothelial
      cells, with electron microscopy evidence of attenuated trophoblast layers. The
      maternal decidual arteries showed increased wall-to-lumen ratios with persistence
      of actin-positive smooth muscle cells. These changes translated into dramatically
      increased vascular resistance in the uterine arteries, as measured by pulse-wave
      Doppler. Collectively, these results support the hypothesis that defects at the
      maternal-fetal interface are primary causal events in preeclampsia, and further
      suggest the BPH/5 model is important for investigations of the underlying
      pathogenic mechanisms in preeclampsia.

PMID- 16957026
TI  - First cell cycles of sea urchin Paracentrotus lividus are dramatically impaired
      by exposure to extremely low-frequency electromagnetic field.
AB  - Exposure of fertilized eggs of the sea urchin Paracentrotus lividus to an
      electromagnetic field of 75-Hz frequency and low amplitudes (from 0.75 to 2.20 mT
      of magnetic component) leads to a dramatic loss of synchronization of the first
      cell cycle, with formation of anomalous embryos linked to irregular separation of
      chromatids during the mitotic events. Because acetylcholinesterase (ACHE) is
      thought to regulate the embryonic first developmental events of the sea urchin,
      its enzymatic activity was assayed in embryo homogenates and decreased by 48%
      when the homogenates were exposed to the same pulsed field. This enzymatic
      inactivation had a threshold of about 0.75 +/- 0.01 mT. The same field threshold
      was found for the effect on the formation of anomalous embryos of P. lividus.
      Moreover, ACHE inhibitors seem to induce the same teratological effects as those
      caused by the field, while blockers of acetylcholine (ACh) receptors are able to
      antagonize those effects. We conclude that one of the main causes of these
      dramatic effects on the early development of the sea urchin by field exposure
      could be the accumulation of ACh due to ACHE inactivation. The crucial role of
      the membrane in determining the conditions for enzyme inactivation is discussed.

PMID- 16957027
TI  - Exposure to drinking water disinfection by-products and pregnancy loss.
AB  - Previous research has suggested that exposure to elevated levels of drinking
      water disinfection by-products (DBPs) may cause pregnancy loss. In 2000-2004, the
      authors conducted a study in three US locations of varying DBP levels and
      evaluated 2,409 women in early pregnancy to assess their tap water DBP
      concentrations, water use, other risk factors, and pregnancy outcome. Tap water
      concentrations were measured in the distribution system weekly or biweekly. The
      authors considered DBP concentration and ingested amount and, for trihalomethanes
      only, bathing/showering and integrated exposure that included ingestion. On the
      basis of 258 pregnancy losses, they did not find an increased risk of pregnancy
      loss in relation to trihalomethane, haloacetic acid, or total organic halide
      concentrations; ingested amounts; or total exposure. In contrast to a previous
      study, pregnancy loss was not associated with high personal trihalomethane
      exposure (> or =75 micro g/liter and > or =5 glasses of water/day) (odds ratio =
      1.1, 95% confidence interval: 0.7, 1.7). Sporadic elevations in risk were found
      across DBPs, most notably for ingested total organic halide (odds ratio = 1.5,
      95% confidence interval: 1.0, 2.2 for the highest exposure quintile). These
      results provide some assurance that drinking water DBPs in the range commonly
      encountered in the United States do not affect fetal survival.

PMID- 16957028
TI  - Invited commentary: disinfection by-products and pregnancy loss--lessons.

PMID- 16957029
TI  - FDJS03 isolates causing an outbreak of aseptic meningitis in China that evolved
      from a distinct Echovirus 30 lineage imported from countries of the Commonwealth
      of Independent States.
AB  - We compared echovirus 30 strains (FDJS03) which caused an outbreak of aseptic
      meningitis in China in 2003 with other human enterovirus B strains. Sequencing of
      the complete genome of FDJS03_84, a representative strain from this outbreak,
      revealed a mosaic structure with a putative recombination spot within the 2B
      gene. It was most similar to a strain of the same serotype, E30-14125-00, in the
      5' half of the genome but was almost equidistant to all strains analyzed in most
      of the 3' half of the genome. Phylogenetic relationships in the 5'-untranslated
      region and the VP1 gene indicated that the FDJS03 isolates were closely related
      to a distinct lineage of E30 which circulated in countries of the Commonwealth of
      Independent States during 1999 and 2000. It is most likely that the ancestor of
      FDJS03 isolates experienced multiple recombination events in the nonstructural
      protein coding region, which were partly observed in the phylogenetic analysis of
      the 3D region.

PMID- 16957030
TI  - Measurement of serum D-arabinitol/creatinine ratios for initial diagnosis and for
      predicting outcome in an unselected, population-based sample of patients with
      Candida fungemia.
AB  - D-Arabinitol (DA) is a useful diagnostic marker for candidiasis in patients with
      neutropenia and other high-risk groups, but its use in unselected patients with a
      broad range of underlying diseases and conditions has not been studied. We used
      an automated enzymatic fluorometric assay to measure serum DA/creatinine ratios
      (DA/cr's) in 30 healthy adults, 100 hospitalized controls without Candida
      fungemia, and 83 patients from a study of all Candida fungemias in Connecticut
      between October 1998 and September 1999. Sixty-three of 83 (76%) fungemic
      patients and 11 of 100 (11%) nonfungemic controls had serum DA/cr's >or=3.9
      microM/mg/dl (mean + 3 standard deviations for 30 healthy adults). High serum
      DA/cr's were less frequent in patients with cancer or fungemia caused by the DA
      nonproducer Candida glabrata than in patients with cancer or fungemia caused by a
      DA producer, C. albicans, C. tropicalis, or C. parapsilosis. The serum DA/cr was
      first >or=3.9 microM/mg/dl before, on the same day as, or after the first
      positive blood culture was drawn for 30 (36%), 22 (27%), and 11 (13%) fungemia
      patients, respectively. Mortality did not differ significantly among the patients
      with high or normal initial or peak serum DA/cr's, but mortality was higher if
      any serum DA/cr value was >or=3.9 microM/mg/dl 3 or more days after the onset of
      fungemia (18/27 versus 4/24 patients, respectively; P < 0.001). We conclude that
      serum DA/cr's are useful both for the initial diagnosis of Candida fungemia and
      for prognostic purposes for unselected patients with a broad range of underlying
      diseases and conditions.

PMID- 16957032
TI  - Use of a multiple restriction fragment length polymorphism method for detecting
      vaccine-derived polioviruses in clinical samples.
AB  - Since the announcement of the WHO program for the global eradication of
      poliomyelitis and the establishment of epidemiological and virological
      surveillance, the emergence and circulation of pathogenic vaccine-derived
      polioviruses (VDPV) presenting >1% nucleotide divergence from the sequence of the
      original vaccine strain have been demonstrated in certain regions. We developed
      and used a multiple restriction fragment length polymorphism (RFLP) method to
      investigate the frequency of these VDPV in a population with a high level of oral
      poliovirus vaccine coverage in northwestern Russia. Modified RFLP profiles were
      found to be strongly correlated with the presence of mutations and recombination
      events in vaccine strains. We found that a substantial proportion of vaccine
      strains had high percentages of nucleotide substitutions (>0.5%), including a
      type 3 VDPV with 1.4% nucleotide divergence. These findings indicate that VDPV or
      pre-VDPV strains are not rare in certain populations with high levels of vaccine
      coverage. The multiple RFLP method appears to be a simple and rapid tool for
      monitoring such strains, which could jeopardize the benefits of the eradication
      program.

PMID- 16957031
TI  - Outbreak of infection by carbapenem-resistant Acinetobacter baumannii producing
      the carbapenemase OXA-58 in Belgium.
AB  - Carbapenem-resistant Acinetobacter baumannii isolates were obtained from 17
      patients between September 2004 and August 2005 at the Academisch Ziekenhuis
      Vrije Universiteit Brussel, Brussels, Belgium. These multidrug-resistant
      isolates, which belonged to a single clone, remained susceptible to colistin and
      tigecycline only and produced the carbapenem-hydrolyzing oxacillinase OXA-58.
      This study highlights the importance of the intercountry spread of this beta
      lactamase-mediated resistance mechanism and its epidemic evolution.

PMID- 16957033
TI  - Group A streptococci from invasive-disease episodes in Poland are remarkably
      divergent at the molecular level.
AB  - Forty-one clinical isolates of group A streptococcus (GAS) were recovered in
      Poland from patients with severe invasive infections and were analyzed by
      phenotypic and genotypic techniques. All isolates were characterized by
      determining their susceptibilities to antimicrobial agents and by determining
      their types by pulsed-field gel electrophoresis, multilocus sequence typing, emm
      typing, and the detection of five streptococcal pyrogenic exotoxin genes (speA,
      speB, speC, speF, ssa). The isolates studied were fully susceptible to penicillin
      G, levofloxacin, quinupristin-dalfopristin, and linezolid. Resistance to
      tetracycline, chloramphenicol, and erythromycin was detected in 46.3, 12.1, and
      9.8% of the isolates, respectively. A total of 23 different emm sequence types
      were identified, of which emm1 and emm12 (19.5% each) were the most common,
      followed by emm81, emm44/61, and emm85. All the emm1 isolates had the speA2
      allele. Twenty-three unrelated sequence types (STs) were identified, with the
      most frequent STs, ST28 and ST36, corresponding to emm1 and emm12, respectively.
      Six newly found STs (STs 375, 376, 377, 378, 379, and 385) corresponded to emm
      types 74, 102, 77, 76, 84 and 63, respectively. The emm1 type and the presence of
      speA2 gene were associated with the severity of GAS infections. This work
      presents the first molecular study on Polish invasive GAS isolates.

PMID- 16957034
TI  - Presence of pathogenicity island genes in Enterococcus faecalis isolates from
      pigs in Denmark.
AB  - Enterococcus faecalis isolates of porcine origin were screened for the presence
      of a previously identified pathogenicity island (PAI). By using the esp gene as a
      genetic marker for the presence of this PAI, 9 esp-positive and 10 esp-negative
      isolates of porcine origin were investigated by use of a designed oligonucleotide
      array. The results indicated the clustering of esp-positive strains by multilocus
      sequence typing (MLST), but surprisingly, all strains investigated contained
      parts of the PAI. None of the strains of animal origin investigated belonged to
      previously identified MLST complex 2, where most isolates from patients cluster.
      Five of the nine esp-positive E. faecalis isolates of animal origin belonged to
      the same PAI complex as human isolate MMH594 but differed in their sequence
      types, which strongly indicates the horizontal transfer of the PAI between
      enterococci of porcine and human origin.

PMID- 16957035
TI  - Characterization of atypical enteropathogenic Escherichia coli strains that
      express typical localized adherence in HeLa cells in the absence of the bundle
      forming pilus.
AB  - The characterization of nine atypical enteropathogenic Escherichia coli strains
      expressing localized adherence in HeLa cells in the absence of the bundle-forming
      pilus revealed a diversity of serotypes, plasmids, and virulence genes. Although
      the strains lacked known E. coli adhesin genes, the identification of new
      adhesins could contribute to the characterization of similar enteropathogenic E.
      coli isolates.

PMID- 16957036
TI  - Usefulness of adult bovine serum for Helicobacter pylori culture media.
AB  - Fetal bovine serum (FBS) and adult bovine serum (BS) exhibited bactericidal
      activity against Helicobacter pylori at various levels, which were higher in BS
      than in FBS. The bactericidal activity was inactivated by heat treatment at 56
      degrees C for 30 min. Our results demonstrated that heat-treated BS is a useful
      serum source of H. pylori culture medium.

PMID- 16957037
TI  - Population-based study of deletions in five different genomic regions of
      Mycobacterium tuberculosis and possible clinical relevance of the deletions.
AB  - Regions of difference (RDs) have been described in clinical isolates of
      Mycobacterium tuberculosis, but the potential epidemiological and clinical
      relevance of the genotypes of these RDs remains to be investigated. We screened a
      population-based sample of 648 isolates for the deletion of five RDs, designated
      RD105, RD181, RD142, RD150, and RD239, using microarray-based hybridization, PCR,
      and DNA sequencing and assessed the associations between the RD deletions and the
      clinical characteristics of the patients using chi-square analysis and
      multivariate logistic regression model. Of the 648 isolates, 18 (2.8%) had the
      RD239 deletion and 39 (6.0%) had the RD105 deletion. The deletions of RD142,
      RD150, and RD181 subdivided the isolates with the RD105 deletion into four groups
      comprising a group with concurrent deletions of RD105, RD181, and RD142 (n = 13);
      a group with concurrent deletions of RD105, RD181, and RD150 (n = 5); a group
      with concurrent deletions of RD105 and RD181 (n = 13); and a group with a
      deletion of RD105 only (n = 8). Extrathoracic tuberculosis is statistically
      significantly associated with infection with the isolates with concurrent
      deletions of RD105, RD181, and RD142 (adjusted odds ratio [OR] = 3.05; 95%
      confidence interval [CI] = 1.58, 5.90) and the isolates with concurrent deletions
      of RD105, RD181, and RD150 (adjusted OR = 11.09; 95% CI = 4.27, 28.80), after
      controlling for the previously identified risk factors for extrathoracic
      tuberculosis (human immunodeficiency virus serostatus, race, gender, and the
      genotype of the plcD gene). These two combinations of RD deletions have the
      potential for predicting the clinical presentation of M. tuberculosis infection
      in the human host.

PMID- 16957038
TI  - Detection of Brugia parasite DNA in human blood by real-time PCR.
AB  - Brugian filariasis (caused by the nematodes Brugia malayi and B. timori) is an
      important cause of disability in Southeast Asia. Improved diagnostic tests are
      needed for filariasis elimination programs (to identify areas of endemicity and
      to monitor progress) and for diagnosis of the disease in infected individuals. We
      have developed and evaluated two real-time PCR assays for detecting Brugia DNA in
      human blood and compared the results of these assays to those of "gold standard"
      assays. One assay uses a TaqMan probe (TaqM) to amplifiy a 320-bp "HhaI repeat"
      DNA sequence. The other assay uses a minor groove binding probe (MGB) and
      modified nucleotides in primers (Eclipse MGB) to amplify a 120-bp fragment of the
      HhaI repeat. This assay detects 22 copies of the target sequence, and it is more
      sensitive than the TaqM assay. Both assays were evaluated with human blood
      samples from two different areas of endemicity. The MGB assay was as sensitive as
      membrane filtration and microscopy for the detection of B. malayi infection in 57
      blood samples recovered at night from patients in Sulawesi, Indonesia. The MGB
      assay also detected parasite DNA in 17 of 31 (55%) of microfilaria-negative day
      blood samples from these subjects. This test was more sensitive than the
      conventional and the TaqM PCRs (and was almost as sensitive as night blood
      membrane filtration) for the detection of infection in 52 blood samples recovered
      at night from individuals in an area of B. timori endemicity on Alor Island,
      Indonesia, where microfilaria-positive individuals had low densities after mass
      treatment. Thus, the Eclipse MGB real-time PCR assay is a sensitive means of
      detecting Brugia parasite DNA in human blood.

PMID- 16957039
TI  - Genotyping hepatitis C viruses from Southeast Asia by a novel line probe assay
      that simultaneously detects core and 5' untranslated regions.
AB  - Hepatitis C viruses (HCVs) display a high level of sequence diversity and are
      currently divided into six genotypes. A line probe assay (LiPA), which targets
      the 5' untranslated region (5'UTR) of the HCV genome, is widely used for
      genotyping. However, this assay cannot distinguish many genotype 6 subtypes from
      genotype 1 due to high sequence similarity in the 5'UTR. We investigated the
      accuracy of a new generation LiPA (VERSANT HCV genotype 2.0 assay), in which
      genotyping is based on 5'UTR and core sequences, by testing 75 selected HCV RNA
      positive sera from Southeast Asia (Vietnam and Thailand). For comparison, sera
      were tested on the 5'UTR based VERSANT HCV genotype assay and processed for
      sequence analysis of the 5'UTR-to-core and NS5b regions as well. Phylogenetic
      analysis of both regions revealed the presence of genotype 1, 2, 3, and 6
      viruses. Using the new LiPA assay, genotypes 6c to 6l and 1a/b samples were more
      accurately genotyped than with the previous test only targeting the 5'UTR (96%
      versus 71%, respectively). These results indicate that the VERSANT HCV genotype
      2.0 assay is able to discriminate genotypes 6c to 6l from genotype 1 and allows a
      more accurate identification of genotype 1a from 1b by using the genotype
      specific core information.

PMID- 16957040
TI  - Cholera due to altered El Tor strains of Vibrio cholerae O1 in Bangladesh.
AB  - We determined the types of cholera toxin (CT) produced by a collection of 185
      Vibrio cholerae O1 strains isolated in Bangladesh over the past 45 years. All of
      the El Tor strains of V. cholerae O1 isolated since 2001 produced CT of the
      classical biotype, while those isolated before 2001 produced CT of the El Tor
      biotype.

PMID- 16957041
TI  - Optimal surveillance culture sites for detection of methicillin-resistant
      Staphylococcus aureus in newborns.
AB  - We describe two outbreaks among newborns, one caused by community-associated
      methicillin-resistant Staphylococcus aureus (MRSA) and the other by hospital
      associated MRSA. The umbilicus, rectum, and nares were tested for colonization.
      We found that no single body site had optimal sensitivity when tested alone. The
      combination of umbilical and nasal swabs achieved a sensitivity of >90%.

PMID- 16957042
TI  - Mixed pulmonary infection with Strongyloides stercoralis and Blastomyces
      dermatitidis.
AB  - We report the first case of mixed pulmonary infection with Strongyloides
      stercoralis and Blastomyces dermatitidis. Histopathology from the lung biopsy
      showed structures consistent with B. dermatitidis and S. stercoralis. A
      parasitology exam from a bronchi alveolar lavage yielded an immature rhabditiform
      larva and female worm. Fungal cultures grew B. dermatitidis.

PMID- 16957043
TI  - Increased vancomycin MICs for Staphylococcus aureus clinical isolates from a
      university hospital during a 5-year period.
AB  - Staphylococcus aureus is one of the most commonly isolated organisms in
      nosocomial infections. While the prevalence of methicillin-resistant S. aureus
      (MRSA) continues to increase worldwide, there is concern about an increase in
      vancomycin MICs among S. aureus strains. The prevalence of MRSA and vancomycin
      MIC trends in S. aureus from patients in a university hospital were analyzed.
      Clinical Laboratory Standards Institute (CLSI, formerly NCCLS) reference broth
      microdilution MIC testing was performed on all clinically relevant S. aureus
      isolates from January 2000 through December 2004. A total of 6,003 S. aureus
      isolates were analyzed. No vancomycin-resistant S. aureus isolates were detected.
      One MRSA isolate had a vancomycin MIC of 8 mug/ml and was confirmed as vancomycin
      intermediate S. aureus. Among the 6,002 remaining isolates, a shift in vancomycin
      MICs from </=0.5 to 1.0 mug/ml was observed during the 5-year period. The
      percentage of S. aureus isolates with a vancomycin MIC of 1 mug/ml in 2004 was
      significantly higher than the percentage of isolates in 2000 (70.4% versus 19.9%;
      P < 0.01). This vancomycin MIC shift was more notable in methicillin-susceptible
      S. aureus. Our 5 years of routine testing of clinical isolates using the CLSI
      reference broth microdilution MIC method demonstrated a tendency toward
      decreasing susceptibility to vancomycin in S. aureus.

PMID- 16957044
TI  - Reverse transcription-PCR-enzyme-linked immunosorbent assay for rapid detection
      and differentiation of alphavirus infections.
AB  - Due to the lack of a rapid, simple, and inexpensive assay for detecting
      alphavirus infections, we combined a reverse transcription-PCR with an enzyme
      linked immunosorbent assay (RT-PCR-ELISA) to identify human pathogenic
      alphaviruses that are endemic in the New World. By combining the sensitivity of
      PCR, the detection simplicity of ELISA, and the specificities of DNA probes, this
      method rapidly detected and differentiated closely related species and subtypes
      of several medically important alphaviruses. After an amplification using RT-PCR
      with primers targeting conserved sequences in the nonstructural protein 1 gene,
      sequence-specific, biotin-labeled probes targeted against Venezuelan, eastern,
      and western equine encephalitis or Mayaro virus genes were used for the detection
      of amplicons using ELISA. The assay is simple, fast, and easy to perform in an
      ordinary diagnostic laboratory or clinical setting. Nucleic acid derived from
      cell cultures infected with several alphaviruses, clinical specimens, and
      mosquito pools as well as frozen and paraffin-embedded animal tissues were
      detected and identified within 6 to 7 h in a sensitive and specific manner.

PMID- 16957045
TI  - Pyrosequencing, a high-throughput method for detecting single nucleotide
      polymorphisms in the dihydrofolate reductase and dihydropteroate synthetase genes
      of Plasmodium falciparum.
AB  - A pyrosequencing protocol was developed as a rapid and reliable method to
      identify the mutations of the dhfr and dhps genes of Plasmodium falciparum that
      are associated with antifolate resistance. The accuracy and specificity of this
      method were tested using six laboratory-cultured P. falciparum isolates harboring
      known single nucleotide polymorphisms (SNPs) in the genes dhfr (codons 50, 51,
      59, 108, and 164) and dhps (codons 436, 437, 540, 581, and 613). The lowest
      threshold for detection of all the SNPs tested by pyrosequencing was the
      equivalent of two to four parasite genomes. Also, this method was highly specific
      for P. falciparum, as it did not amplify any DNA products from the other species
      of human malaria parasites. We also mixed wild-type and mutant-type parasite DNAs
      in various proportions to determine how pyrosequencing, restriction fragment
      length polymorphism (RFLP), and direct conventional sequencing (for dhfr)
      compared with each other in detecting different SNPs in the mixture. In general,
      pyrosequencing and RFLP showed comparable sensitivities in detecting most of the
      SNPs in dhfr except for the 164L mutation, which required at least twice the
      amount of DNA for pyroseqencing as for RFLP. For detecting SNPs in dhps,
      pyrosequencing was slightly more sensitive than RFLP and direct sequencing.
      Overall, pyrosequencing was faster and less expensive than either RFLP or direct
      sequencing. Thus, pyrosequencing is a practical alternative method that can be
      used in a high-throughput format for molecular surveillance of antimalarial-drug
      resistance.

PMID- 16957046
TI  - Emergence and outbreaks of CTX-M beta-lactamase-producing Escherichia coli and
      Klebsiella pneumoniae strains in a Tunisian hospital.
AB  - Sixty-two isolates of Enterobacteriaceae (35 Escherichia coli and 27 Klebsiella
      pneumoniae isolates) producing CTX-M-type beta-lactamases were collected between
      March 2000 and June 2003 in different wards of Charles Nicolle Hospital in Tunis
      (Tunisia). Sequencing identified the bla(CTX-M-15) determinant in 55 isolates and
      bla(CTX-M-16) in 7 isolates. The CTX-M-15-producing strains were isolated in
      several wards and consisted mainly of two successive clonal groups of E. coli and
      a major clonal group of K. pneumoniae. The second clonal group of E. coli
      belonged to phylogenetic group B2 and harbored more virulence factors than the
      first clonal group. Among the 22 transconjugants or electroporants obtained with
      selected E. coli and K. pneumoniae CTX-M-15-producing strains, a predominant
      plasmid restriction pattern was obtained with 17 isolates. The four CTX-M-16
      producing strains of E. coli yielded the same pulsed-field gel electrophoresis
      (PFGE) pattern, while the three CTX-M-16-producing strains of K. pneumoniae
      yielded two different PFGE patterns. All of the CTX-M-16-producing isolates were
      recovered in the pediatric ward and had the same plasmid restriction pattern.

PMID- 16957047
TI  - Gene diversity and mode of reproduction in the brooded larvae of the coral
      Heteroxenia fuscescens.
AB  - The soft coral Heteroxenia fuscescens is a common shallow-reef brooding species
      in the Red Sea. By means of amplified fragment length polymorphism markers, we
      studied modes of reproduction of planulae (sexual vs. vegetative) and levels of
      gene diversity of a population residing in the northern Gulf of Eilat, Red Sea.
      Eighty-nine larvae were collected from 9 mother colonies at 3 locations over a
      distance of 5 km. Amplifications revealed 221 putative loci, of which 81.4% were
      polymorphic; gene diversity was 0.29, allowing good identification of individual
      genotypes. No 2 identical DNA samples were present, so no asexual reproduction of
      planulae was indicated. The sampled planulae did not exhibit any genetic
      structure characteristic to a specific location, indicating one large gene pool
      and extensive gene flow among H. fuscescens specimens inhabiting the northern
      Gulf of Eilat.

PMID- 16957048
TI  - Inbreeding linked to amphibian survival in the wild but not in the laboratory.
AB  - We examined the effects of inbreeding on the performance of wood frog (Rana
      sylvatica) larvae in the field and in the laboratory. We used microsatellite
      analysis to establish the parentage and degree of inbreeding of the larvae. Two
      different estimators of inbreeding were used. The first was based on average
      multilocus heterozygosity, and the second was based on a molecular relatedness
      estimator. The estimators were highly correlated, and both showed a significant
      negative relationship between inbreeding and survival in the wild. However, there
      was no evidence that inbreeding influenced growth or development in the wild.
      Neither was there any evidence that inbreeding affected survival, growth, or
      development in the laboratory. These results suggest that, for wood frogs,
      inbreeding has a bigger effect on fitness in the wild than in captivity and that
      measurements of survival are more sensitive than measures of growth or
      development.

PMID- 16957049
TI  - Developmental competence of human in vitro aged oocytes as host cells for nuclear
      transfer.
AB  - BACKGROUND: Improving human nuclear transfer (NT) efficiencies is paramount for
      the development of patient-specific stem cell lines, although the opportunities
      remain limited owing to difficulties in obtaining fresh mature oocytes. METHODS:
      Therefore, the developmental competence of aged, failed-to-fertilize human
      oocytes as an alternate cytoplasmic source for NT was assessed and compared with
      use of fresh, ovulation-induced oocytes. To further characterize the
      developmental potential of aged oocytes, parthenogenetic activation,
      immunocytochemical analysis of essential microtubule proteins involved in meiotic
      and mitotic division, and RT-PCR in single oocytes (n = 6) was performed to
      determine expression of oocyte-specific genes [oocyte-specific histone 1 (H1FOO),
      growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15),
      zygote arrest 1 (ZAR1)] and microtubule markers [nuclear mitotic arrest (NuMA),
      minus-end directed motor protein HSET and the microtubule kinesin motor protein
      EG5]. RESULTS: For NT, enucleation and fusion rates of aged oocytes were
      significantly lower compared with fresh oocytes (P < 0.05). Cleavage rates and
      subsequent development were poor. In addition, parthenote cleavage was low.
      Immunocytochemical analysis revealed that many oocytes displayed aberrant
      expression of NuMA and EG5, had disrupted meiotic spindles and tetrapolar
      spindles. One of the six oocytes misexpressed GDF9, BMP15 and ZAR1. Two oocytes
      expressed EG5 messenger RNA (mRNA), and HSET and NuMA were not detectable. RT-PCR
      of mRNA for oocyte specific genes and microtubule markers in single aged oocytes.
      CONCLUSIONS: Thus, aneuploidy and spindle defects may contribute to poor
      parthenogenetic development and developmental outcomes following NT.

PMID- 16957050
TI  - e-Talking to patients: connecting with the health care consumer.

PMID- 16957051
TI  - Erv26p directs pro-alkaline phosphatase into endoplasmic reticulum-derived coat
      protein complex II transport vesicles.
AB  - Secretory proteins are exported from the endoplasmic reticulum (ER) in transport
      vesicles formed by the coat protein complex II (COPII). We detected Erv26p as an
      integral membrane protein that was efficiently packaged into COPII vesicles and
      cycled between the ER and Golgi compartments. The erv26Delta mutant displayed a
      selective secretory defect in which the pro-form of vacuolar alkaline phosphatase
      (pro-ALP) accumulated in the ER, whereas other secretory proteins were
      transported at wild-type rates. In vitro budding experiments demonstrated that
      Erv26p was directly required for packaging of pro-ALP into COPII vesicles.
      Moreover, Erv26p was detected in a specific complex with pro-ALP when
      immunoprecipitated from detergent-solublized ER membranes. Based on these
      observations, we propose that Erv26p serves as a transmembrane adaptor to link
      specific secretory cargo to the COPII coat. Because ALP is a type II integral
      membrane protein in yeast, these findings imply that an additional class of
      secretory cargo relies on adaptor proteins for efficient export from the ER.

PMID- 16957052
TI  - The Ca2+-binding protein ALG-2 is recruited to endoplasmic reticulum exit sites
      by Sec31A and stabilizes the localization of Sec31A.
AB  - The formation of transport vesicles that bud from endoplasmic reticulum (ER) exit
      sites is dependent on the COPII coat made up of three components: the small
      GTPase Sar1, the Sec23/24 complex, and the Sec13/31 complex. Here, we provide
      evidence that apoptosis-linked gene 2 (ALG-2), a Ca(2+)-binding protein of
      unknown function, regulates the COPII function at ER exit sites in mammalian
      cells. ALG-2 bound to the Pro-rich region of Sec31A, a ubiquitously expressed
      mammalian orthologue of yeast Sec31, in a Ca(2+)-dependent manner and colocalized
      with Sec31A at ER exit sites. A Ca(2+) binding-deficient ALG-2 mutant, which did
      not bind Sec31A, lost the ability to localize to ER exit sites. Overexpression of
      the Pro-rich region of Sec31A or RNA interference-mediated Sec31A depletion also
      abolished the ALG-2 localization at these sites. In contrast, depletion of ALG-2
      substantially reduced the level of Sec31A associated with the membrane at ER exit
      sites. Finally, treatment with a cell-permeable Ca(2+) chelator caused the
      mislocalization of ALG-2, which was accompanied by a reduced level of Sec31A at
      ER exit sites. We conclude that ALG-2 is recruited to ER exit sites via Ca(2+)
      dependent interaction with Sec31A and in turn stabilizes the localization of
      Sec31A at these sites.

PMID- 16957053
TI  - Targeted comparative RNA interference analysis reveals differential requirement
      of genes essential for cell proliferation.
AB  - Differences in the genetic and epigenetic make up of cell lines have been very
      useful for dissecting the roles of specific genes in the biology of a cell.
      Targeted comparative RNAi (TARCOR) analysis uses high throughput RNA interference
      (RNAi) against a targeted gene set and rigorous quantitation of the phenotype to
      identify genes with a differential requirement for proliferation between cell
      lines of different genetic backgrounds. To demonstrate the utility of such an
      analysis, we examined 257 growth-regulated genes in parallel in a breast
      epithelial cell line, MCF10A, and a prostate cancer cell line, PC3. Depletion of
      an unexpectedly high number of genes (25%) differentially affected proliferation
      of the two cell lines. Knockdown of many genes that spare PC3 (p53-) but inhibit
      MCF10A (p53+) proliferation induces p53 in MCF10A cells. EBNA1BP2, involved in
      ribosome biogenesis, is an example of such a gene, with its depletion arresting
      MCF10A at G1/S in a p53-dependent manner. TARCOR is thus useful for identifying
      cell type-specific genes and pathways involved in proliferation and also for
      exploring the heterogeneity of cell lines. In particular, our data emphasize the
      importance of considering the genetic status, when performing siRNA screens in
      mammalian cells.

PMID- 16957054
TI  - Caenorhabditis elegans DYF-2, an orthologue of human WDR19, is a component of the
      intraflagellar transport machinery in sensory cilia.
AB  - The intraflagellar transport (IFT) machinery required to build functional cilia
      consists of a multisubunit complex whose molecular composition, organization, and
      function are poorly understood. Here, we describe a novel tryptophan-aspartic
      acid (WD) repeat (WDR) containing IFT protein from Caenorhabditis elegans, DYF-2,
      that plays a critical role in maintaining the structural and functional integrity
      of the IFT machinery. We determined the identity of the dyf-2 gene by transgenic
      rescue of mutant phenotypes and by sequencing of mutant alleles. Loss of DYF-2
      function selectively affects the assembly and motility of different IFT
      components and leads to defects in cilia structure and chemosensation in the
      nematode. Based on these observations, and the analysis of DYF-2 movement in a
      Bardet-Biedl syndrome mutant with partially disrupted IFT particles, we conclude
      that DYF-2 can associate with IFT particle complex B. At the same time, mutations
      in dyf-2 can interfere with the function of complex A components, suggesting an
      important role of this protein in the assembly of the IFT particle as a whole.
      Importantly, the mouse orthologue of DYF-2, WDR19, also localizes to cilia,
      pointing to an important evolutionarily conserved role for this WDR protein in
      cilia development and function.

PMID- 16957056
TI  - Nonhomogeneous birth and death models for epidemic outbreak data.
AB  - In this paper, generalized nonlinear models are proposed in order to incorporate
      the following considerations in modeling an epidemic disease outbreak
      statistically. (1) The dependence of the data is handled with a nonhomogeneous
      death or a nonhomogeneous birth process. (2) The first stage of the outbreak is
      described with an epidemic susceptibles-infectives-removed (SIR) model. Soon the
      control measures taken will dominate the process. These measures are in addition
      to the natural epidemic removal process. The prevalence is related to the
      censored infection times in such a way that the distribution function and thus
      the survival function satisfy approximately the first equation of the SIR model.
      This leads in a natural way to the Burr family of distributions. (3) The
      nonhomogeneous birth process handles the fact that in practice, with some delay,
      infecteds are registered, but not susceptibles. (4) Finally, the ending of the
      epidemic caused by the measures taken is incorporated through a modification of
      the survival function with a final-size parameter, in the same way as is done in
      long-term survival models. These models are applied to three outbreaks: The Dutch
      classical swine fever outbreak from 1997 to 1998, the foot- and-mouth disease
      outbreak in Great Britain from 2001, and the Dutch avian influenza (H7N7)
      outbreak from 2003.

PMID- 16957055
TI  - Sphingosine 1-phosphate induces myoblast differentiation through Cx43 protein
      expression: a role for a gap junction-dependent and -independent function.
AB  - Although sphingosine 1-phosphate (S1P) has been considered a potent regulator of
      skeletal muscle biology, acting as a physiological anti-mitogenic and
      prodifferentiating agent, its downstream effectors are poorly known. In the
      present study, we provide experimental evidence for a novel mechanism by which
      S1P regulates skeletal muscle differentiation through the regulation of gap
      junctional protein connexin (Cx) 43. Indeed, the treatment with S1P greatly
      enhanced Cx43 expression and gap junctional intercellular communication during
      the early phases of myoblast differentiation, whereas the down-regulation of Cx43
      by transfection with short interfering RNA blocked myogenesis elicited by S1P.
      Moreover, calcium and p38 MAPK-dependent pathways were required for S1P-induced
      increase in Cx43 expression. Interestingly, enforced expression of mutated
      Cx43(Delta130-136) reduced gap junction communication and totally inhibited S1P
      induced expression of the myogenic markers, myogenin, myosin heavy chain,
      caveolin-3, and myotube formation. Notably, in S1P-stimulated myoblasts,
      endogenous or wild-type Cx43 protein, but not the mutated form,
      coimmunoprecipitated and colocalized with F-actin and cortactin in a p38 MAPK
      dependent manner. These data, together with the known role of actin remodeling in
      cell differentiation, strongly support the important contribution of gap
      junctional communication, Cx43 expression and Cx43/cytoskeleton interaction in
      skeletal myogenesis elicited by S1P.

PMID- 16957057
TI  - The use of three-dimensional imaging in orthodontics.
AB  - The article illustrates the value of three-dimensional imaging of the face and
      jaws in the diagnosis and treatment of patients. The applications of programs
      that have been written for the analysis of facial form are also described,
      including registration and prediction. The use of the Procrustes analysis is
      demonstrated in groups of children and adults to differentiate between male and
      female facial morphology. The use of scanning in forensic science is also
      described. The application of surface shape analysis to groups of monozygotic and
      dizygotic twins and to family studies to detect those areas that are genetically
      determined from those areas, which are not, is illustrated.

PMID- 16957058
TI  - Evaluation of cervical posture following palatal expansion: a 12-month follow-up
      controlled study.
AB  - This study evaluated the effects of rapid palatal expansion (RPE) on
      nasopharyngeal airway size, head posture, and cervical curvature angle in
      children with nasal obstruction. The patients were 45 female subjects (8-15 years
      of age) who had a reduced nasopharyngeal airway size and were subjectively
      assessed as being mouth breathers and requiring palatal expansion. They were
      randomly allocated to one of two groups: 23 subjects in the first group were
      treated with RPE, while the 22 subjects in the other group were monitored for
      approximately 14 months prior to commencing therapy, and became untreated
      controls. Lateral skull radiographs, taken in the natural head position, were
      obtained at the first visit (T0) and 6 (T1) and 12 (T2) months later for all
      subjects. The differences between the cephalometric variables at baseline and
      after 6 and 12 months were evaluated with a one-way repeated measures analysis of
      variance. Where significant interactions were found, a Bonferroni corrected
      paired Student's t-test was performed for pairwise comparisons. Changes in
      cephalometric variables within the experimental groups were tested by paired
      Student's t-tests as a post hoc procedure. Finally, a correlation matrix, using
      the Pearson correlation coefficient, was computed in order to evaluate the
      relationship between the change in airway adequacy and (1) the amount of
      maxillary expansion, (2) chronological age, (3) the amount of time that the
      appliance was activated, and (4) morphological and postural measurements of the
      face. At T1, children under active treatment showed a statistically significant
      increase in nasopharyngeal airway size, cervical curvature angle, and flexion of
      the head, together with a significant decrease in craniocervical angulation (all
      P < 0.05). These changes were all found to be stable at T2. No significant
      changes were seen in the control group. The correlation coefficients indicated a
      significant correlation between nasopharyngeal airway size and craniocervical
      angulation (SN/OPT angle; r = -0.61, P < 0.05). The findings indicate that RPE is
      capable of increasing nasopharyngeal airway size in young females, which results
      in a decrease in craniocervical angulation. Clinically, the findings seem to
      suggest that improvement of respiratory function could result in a change in head
      posture.

PMID- 16957059
TI  - Maxillary third molar position in Class II malocclusions: the effect of treatment
      with and without maxillary premolar extractions.
AB  - The present study compared the number of erupted and functioning maxillary third
      molars and their mesio-distal angulation in patients with Class II malocclusions
      orthodontically treated with and without extraction of two maxillary premolars
      and fixed appliances. For that purpose, the records of 55 patients were selected,
      which were divided into two groups. Group 1 was treated without extractions and
      comprised 28 patient records (19 males and 9 females), with a mean age of 19.03
      years [standard deviation (SD) = 2.33], treatment time of 2.59 years (SD = 1.08),
      and follow-up time of 6.48 years (SD = 2.42). Group 2 was treated with
      extractions and comprised 27 patient records (14 males and 13 females), with a
      mean age of 19.94 years (SD = 2.87), treatment time of 2.95 years (SD = 1.17),
      and follow-up time of 5.88 years (SD = 2.96). Analysis of the erupted and
      functioning maxillary third molars was conducted on the maxillary and mandibular
      dental casts. The mesio-distal angulations of the maxillary third molars were
      assessed on panoramic radiographs with the presence of both maxillary third
      molars. The results demonstrated that the number of erupted and functioning
      maxillary third molars was statistically greater (P = 0.01) in Class II subjects
      treated with extraction of maxillary premolars, when compared with those treated
      without extractions. The patients treated with two maxillary premolar extractions
      presented significantly smaller third molar mesio-distal angulations, that are
      more favourable to eruption, than those treated non-extraction.

PMID- 16957060
TI  - Visualizing three-dimensional facial soft tissue changes following orthognathic
      surgery.
AB  - Laser scanning can be used to visualize the face in three dimensions. These scans
      can then be processed to enable assessment of facial changes. The aim of this
      single-centre, prospective, longitudinal, cohort study was to investigate whether
      four different visualization methods correctly represented facial changes
      occurring as a result of orthognathic surgery. Twenty-six consecutive
      orthognathic patients (13 female mandibular advancement and 13 male bimaxillary
      Class III) were included as well as a control group of 12 non-growing adults (6
      males and 6 females). Pre- and post-operative facial laser scans were
      superimposed and four different visualization methods applied: correspondences
      with sensitivity to movement, normals, radial, and closest point. A group of 10
      'blinded' observers determined the surgical procedure (if any) that had been
      performed by applying a specific colour scale to each facial image. The
      sensitivities and specificities for each visualization method applied to each
      subject group were determined. The intraobserver repeatability was investigated
      using Cohen's kappa (k). The radial method was found to be superior for
      identifying mandibular advancement patients (sensitivity/specificity 58.5/92.4
      per cent), the normals method for visualization of bimaxillary Class III cases
      (26.2/99.6 per cent), while the control group was best represented using the
      closest point (60.0/80.8 per cent). Overall, intraobserver repeatability was good
      (k = 0.61). A good level of repeatability was demonstrated in the separate
      subject groups (mandibular advancement 0.70, bimaxillary Class III 0.70, and
      controls 0.62). There was no significant difference in the abilities of the four
      visualization methods to represent facial changes. Each method allowed correct
      identification of different proportions of the subject groups.

PMID- 16957061
TI  - National serosurvey of cytomegalovirus in Australia.
AB  - In anticipation of the development of a vaccine against cytomegalovirus (CMV), we
      conducted a large, nationally representative serosurvey to examine the
      seroprevalence of CMV in Australia. Sera were collected opportunistically from
      laboratories around Australia. Age- and gender-representative samples were tested
      for CMV antibody. The population-weighted rate of CMV seropositivity in subjects
      between 1 and 59 years of age was 57% (95% confidence interval, 55.2 to 58.6%).
      An association between CMV seroprevalence and increasing age was recognized;
      however, little overall difference in seroprevalence between the sexes was found.
      The finding that high levels of CMV exposure occur in the first few years of life
      suggests that for a universal vaccination program to have maximal impact, the
      vaccine would need to be delivered to infants and have a long duration of
      protective efficacy. This is the first national serosurvey looking at
      cytomegalovirus in the Australian community. This study provides valuable
      information that can be used to examine the incidence of infection in the
      community and help focus the administration of a future CMV vaccine to
      appropriate target populations.

PMID- 16957062
TI  - Validation of a competitive enzyme-linked immunosorbent assay for detection of
      antibodies against Babesia bovis.
AB  - A previously developed competitive enzyme-linked immunosorbent assay (cELISA)
      based on a species-specific, broadly conserved, and tandemly repeated B-cell
      epitope within the C terminus of rhoptry-associated protein 1 of Babesia bovis
      was refined and validated for use internationally. Receiver operating
      characteristic analysis revealed an assay with a specificity and positive
      predictive value of 100% and a sensitivity of 91.1%, with various negative
      predictive values depending on the level of disease prevalence. The cELISA was
      distributed to four different laboratories, along with a reference set of 100
      defined bovine sera, including known-positive, known-negative, and field samples.
      Pairwise concordances among the four laboratories ranged from 94% to 88%.
      Analysis of variance of the resulting optical densities and a test of homogeneity
      indicated no significant difference among the laboratories. Overall, the cELISA
      appears to have the attributes necessary for international application.

PMID- 16957063
TI  - An open question.

PMID- 16957064
TI  - Why open access to research and scholarship?

PMID- 16957065
TI  - Nonlinear interaction between shunting and adaptation controls a switch between
      integration and coincidence detection in pyramidal neurons.
AB  - The membrane conductance of a pyramidal neuron in vivo is substantially increased
      by background synaptic input. Increased membrane conductance, or shunting, does
      not simply reduce neuronal excitability. Recordings from hippocampal pyramidal
      neurons using dynamic clamp revealed that adaptation caused complete cessation of
      spiking in the high conductance state, whereas repetitive spiking could persist
      despite adaptation in the low conductance state. This behavior was reproduced in
      a phase plane model and was explained by a shunting-induced increase in voltage
      threshold. The increase in threshold allows greater activation of the M current
      (I(M)) at subthreshold potentials and reduces the minimum adaptation required to
      stabilize the system; in contrast, activation of the afterhyperpolarization
      current is unaffected by the increase in threshold and therefore remains unable
      to stop repetitive spiking. The nonlinear interaction between shunting and I(M)
      has other important consequences. First, timing of spikes elicited by brief
      stimuli is more precise when background spikes elicited by sustained input are
      prohibited, as occurs exclusively with I(M)-mediated adaptation in the high
      conductance state. Second, activation of I(M) at subthreshold potentials, which
      is increased in the high conductance state, hyperpolarizes average membrane
      potential away from voltage threshold, allowing only large, rapid fluctuations to
      reach threshold and elicit spikes. These results suggest that the shift from a
      low to high conductance state in a pyramidal neuron is accompanied by a switch
      from encoding time-averaged input with firing rate to encoding transient inputs
      with precisely timed spikes, in effect, switching the operational mode from
      integration to coincidence detection.

PMID- 16957066
TI  - Orientation-specific computation in stereoscopic vision.
AB  - The left and right eyes receive subtly different images from a visual scene.
      Binocular disparities of retinal image locations are correlated with variation in
      the depth of objects in the scene and make stereoscopic depth perception
      possible. Disparity stereoscopically specifies a stimulus; changing the stimulus
      in a way that conserves its disparity leaves the stimulus stereoscopically
      unchanged. Therefore, a person's ability to use stereo to see the depth
      separating any two objects should depend only on the disparities of the objects,
      which in turn depend on where the objects are, not what they are. However, I find
      that the disparity difference between two stimuli by itself predicts neither
      stereoacuity nor perceived depth. Human stereo vision is shown here to be most
      sensitive at detecting the relative depth of two gratings when they are parallel.
      Rotating one grating by as little as 10 degrees lowers sensitivity. The rotation
      can make a perceptible depth separation invisible, although it changes neither
      the relative nor absolute disparities of the gratings, only their relative
      orientations. The effect of relative orientation is not confined to stimuli that,
      like gratings, vary along one dimension or to stimuli perceived to have a
      dominant orientation. Rather, it is the relative orientation of the one
      dimensional components of stimuli, even broadband stimuli, that matters. This
      limit on stereoscopic depth perception appears to be intrinsic to the visual
      system's computation of disparity; by taking place within orientation bands, the
      computation renders the coding of disparity inseparable from the coding of
      orientation.

PMID- 16957067
TI  - Cerebellar contributions to locomotor adaptations during splitbelt treadmill
      walking.
AB  - Locomotor adaptability ranges from the simple and fast-acting to the complex and
      long-lasting and is a requirement for successful mobility in an unpredictable
      environment. Several neural structures, including the spinal cord, brainstem,
      cerebellum, and motor cortex, have been implicated in the control of various
      types of locomotor adaptation. However, it is not known which structures control
      which types of adaptation and the specific mechanisms by which the appropriate
      adjustments are made. Here, we used a splitbelt treadmill to test cerebellar
      contributions to two different forms of locomotor adaptation in humans. We found
      that cerebellar damage does not impair the ability to make reactive feedback
      driven motor adaptations, but significantly disrupts predictive feedforward motor
      adaptations during splitbelt treadmill locomotion. Our results speak to two
      important aspects of locomotor control. First, we have demonstrated that
      different levels of locomotor adaptability are clearly dissociable. Second, the
      cerebellum seems to play an essential role in predictive but not reactive
      locomotor adjustments. We postulate that reactive adjustments may instead be
      predominantly controlled by lower neural centers, such as the spinal cord or
      brainstem.

PMID- 16957068
TI  - The role of feedback in shaping the extra-classical receptive field of cortical
      neurons: a recurrent network model.
AB  - The responses of neurons in sensory cortices are affected by the spatial context
      within which stimuli are embedded. In the primary visual cortex (V1), orientation
      selective responses to stimuli in the receptive field (RF) center are suppressed
      by similarly oriented stimuli in the RF surround. Surround suppression, a likely
      neural correlate of perceptual figure-ground segregation, is traditionally
      thought to be generated within V1 by long-range horizontal connections. Recently
      however, it has been shown that these connections are too short and too slow to
      mediate fast suppression from distant regions of the RF surround. We use an
      anatomically and physiologically constrained recurrent network model of macaque
      V1 to show how interareal feedback connections, which are faster and longer-range
      than horizontal connections, can generate "far" surround suppression. We provide
      a novel solution to the puzzle of how surround suppression can arise from
      excitatory feedback axons contacting predominantly excitatory neurons in V1. The
      basic mechanism involves divergent feedback connections from the far surround
      targeting pyramidal neurons sending monosynaptic horizontal connections to
      excitatory and inhibitory neurons in the RF center. One of several predictions of
      our model is that the "suppressive far surround" is not always suppressive, but
      can facilitate the response of the RF center, depending on the amount of
      excitatory drive to the local inhibitors. Our model provides a general mechanism
      of how top-down feedback signals directly contribute to generating cortical
      neuron responses to simple sensory stimuli.

PMID- 16957069
TI  - Contrasting roles of corticosteroid receptors in hippocampal plasticity.
AB  - Elevated levels of corticosteroid hormones, presumably occupying both
      mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs), have been
      reported to impair synaptic plasticity in the hippocampus as well as the
      acquisition of hippocampus-dependent memories. In contrast, recent evidence
      suggests that activation of MRs enhance cognitive functions. To clarify the roles
      of different steroid receptors in hippocampal plasticity, young adult rats were
      injected with the GR antagonist RU38486 (mifepristone) or the MR antagonist
      Spironolactone before the exposure to an acute swim stress. Hippocampal responses
      to perforant path stimulation were then recorded in anesthetized rats. Stress
      combined with RU38486 produced a striking facilitation of LTP. Spironolactone
      enabled only short-term potentiation that reversed to long-term depression (LTD)
      in the stressed animals. Finally, the blockade of both MRs and GRs led to
      impairment of long-term potentiation. These findings indicate that MRs and GRs
      assume opposite roles in regulation of synaptic plasticity after acute exposure
      to stressors.

PMID- 16957070
TI  - High levels of new neuron addition persist when the sensitive period for song
      learning is experimentally prolonged.
AB  - Socially reared zebra finch males imitate a song they hear during posthatching
      days 30-65; during this time, many new neurons are added to the high vocal center
      (HVC), a forebrain nucleus necessary for the production of learned song. New
      neuron addition drops sharply after day 65, and no new songs are imitated. In
      contrast, male zebra finches reared in isolation from other males have more
      variable songs at day 65 and thereafter can still imitate new sounds (Eales,
      1985). We show that, in isolate birds, a greater number of new neurons continues
      to be added to HVC during the next 85 d, and this number correlates with syllable
      variability. We suggest that new neuron addition and turnover facilitate song
      change and that this effect lingers when an expected learning event is delayed.

PMID- 16957071
TI  - The effect of lateral septum corticotropin-releasing factor receptor 2 activation
      on anxiety is modulated by stress.
AB  - Corticotropin-releasing factor (CRF), a 41 amino acid peptide, mediates
      endocrine, autonomic, and behavioral responses to stress. Whereas the CRF1
      receptor appears to contribute to anxiety associated with stress, the role of the
      CRF2 receptor remains unclear and may depend on drug dose, brain location, or
      testing environment. Results involving treatments with selective CRF2 receptor
      agonists or antagonists and the behavior of CRF2 receptor knock-out mice suggest
      both anxiogenic and anxiolytic effects of CRF2 receptor activation. The present
      study tested the hypothesis that the effect of CRF2 receptor activation on
      anxiety depends on the stress level of the animal. The selective CRF2 receptor
      agonist urocortin 2 was infused into the lateral septum of mice under low- or
      high-stress (30 min of immobilization) testing conditions, and then behavior in
      the light-dark box, open-field, and novel-object tests was assessed. In the low
      stress environment, 240 pmol of septal urocortin 2 increased anxiety, but lower
      doses (0.48, 4.8, and 48 pmol) did not have consistent effects. However, in the
      high-stress condition, 48 pmol of septal urocortin 2 significantly increased
      anxiety compared with control in wild-type but not CRF2 receptor knock-out mice
      in the light-dark box. Septal administration of the relatively selective CRF2
      antagonist astressin-2B, but not the CRF1-selective antagonist antalarmin,
      blocked the anxiogenic effects of urocortin 2. Urocortin 2 infusion into the
      medial septum or lateral ventricle did not affect anxiety measures. These results
      indicate that the effect of septal CRF2 receptor activation on anxiety is
      dependent on stress level.

PMID- 16957072
TI  - Photic regulation of arylalkylamine N-acetyltransferase binding to 14-3-3
      proteins in retinal photoreceptor cells.
AB  - 14-3-3 proteins are a ubiquitous, highly conserved family of chaperone proteins
      involved in signal transduction, regulation of cell cycle, intracellular
      trafficking/targeting, cytoskeletal structure, and transcription. Although 14-3-3
      proteins are among the most abundant proteins in the CNS, very little is known
      about their functional roles in the vertebrate retina. In the present study, we
      demonstrated that photoreceptors express 14-3-3 protein(s) and identified a 14-3
      3 binding partner in photoreceptor cells, the melatonin-synthesizing enzyme
      arylalkylamine N-acetyltransferase (AANAT). Importantly, our data demonstrate
      that the binding of 14-3-3 to AANAT is regulated by light, with dramatic
      functional consequences. During the night in darkness, retinal AANAT is
      phosphorylated and forms a complex with 14-3-3 proteins with an apparent
      molecular weight of approximately 90 kDa. Phosphorylation of AANAT facilitates
      the binding of enzyme to 14-3-3 proteins. Within the complex, AANAT is
      catalytically activated and protected from dephosphorylation and degradation.
      Light disrupts the AANAT/14-3-3 complex, leading to catalytic inactivation,
      dephosphorylation, and proteolytic degradation of the enzyme. In the presence of
      the proteasome inhibitor, lactacystin, light results in the formation of a high
      molecular weight complex (>150 kDa), which may represent an intermediate in the
      AANAT degradation process. These findings provide new insight into the roles of
      14-3-3 proteins in photoreceptor cells and to the mechanisms controlling
      melatonin synthesis in the vertebrate retina.

PMID- 16957073
TI  - Differential encoding mechanisms for subsequent associative recognition and free
      recall.
AB  - Recent neuroimaging studies have successfully identified encoding mechanisms that
      support different forms of subsequent episodic recognition memory. In our
      everyday lives, however, much of our episodic memory retrieval is accomplished by
      means of free recall, i.e., retrieval without an external recognition cue. In
      this study, we used functional magnetic resonance imaging to investigate the
      encoding mechanisms that support later free recall and their relationship to
      those that support different forms of later recognition memory. First, in
      agreement with previous work, we found that activation in the left inferior
      frontal gyrus and hippocampus correlated with later associative/relational
      recognition. In these regions, activation was further enhanced for items later
      freely recalled, pointing to shared underlying relational encoding mechanisms
      whose magnitude of activation differentiates later successful free recall from
      successful associative recognition. Critically, we also found evidence for free
      recall-specific encoding mechanisms that did not, in our paradigm, support later
      associative recognition compared with item recognition. These free recall
      specific effects were observed in left mid/dorsolateral prefrontal (DLPFC) and
      bilateral posterior parietal cortices (PPC). We speculate that the higher-level
      working memory operations associated with DLPFC and attention to internal
      mnemonic representations perhaps mediated via PPC may serve to embed an item into
      a rich associative network during encoding that facilitates later access to the
      item. Finally, activation in the perirhinal cortex correlated with successful
      associative binding regardless of the form of later memory, i.e., recognition or
      free recall, providing novel evidence for the role of the perirhinal cortex in
      episodic intra-item encoding.

PMID- 16957074
TI  - Ambiguous encoding of stimuli by primary sensory afferents causes a lack of
      independence in the perception of multiple stimulus attributes.
AB  - Accurate sensory perception often depends on the independent encoding and
      subsequent integration of multiple stimulus attributes. In the weakly electric
      fish Eigenmannia, P- and T-type primary afferent fibers are specialized for
      encoding the amplitude and phase, respectively, of electrosensory stimuli. We
      used a stimulus estimation technique to quantify the ability of P- and T-units to
      encode random modulations in amplitude and phase. As expected, P-units exhibited
      a clear preference for encoding amplitude modulations, whereas T-units exhibited
      a clear preference for encoding phase modulations. Surprisingly, both types of
      afferents also encoded their nonpreferred stimulus attribute when it was
      presented in isolation or when the preferred stimulus attribute was sufficiently
      weak. Because afferent activity can be affected by modulations in either
      amplitude or phase, it is not possible to unambiguously distinguish between these
      two stimulus attributes by observing the activity of a single afferent fiber.
      Simple model neurons with a preference for encoding either amplitude or phase
      also encoded their nonpreferred stimulus attribute when it was presented in
      isolation, suggesting that such ambiguity is unavoidable. Using the well known
      jamming avoidance response as a probe of electrosensory perception, we show that
      the ambiguity at the single-neuron level gives rise to a systematic
      misrepresentation of stimuli at the population level and a resulting
      misperception of the amplitude and phase of electrosensory stimuli.

PMID- 16957075
TI  - Unipolar brush cells of the cerebellum are produced in the rhombic lip and
      migrate through developing white matter.
AB  - Unipolar brush cells (UBCs) are glutamatergic interneurons in the cerebellar
      cortex and dorsal cochlear nucleus. We studied the development of UBCs, using
      transcription factor Tbr2/Eomes as a marker for UBCs and their progenitors in
      embryonic and postnatal mouse cerebellum. Tbr2+ UBCs appeared to migrate out of
      the upper rhombic lip via two cellular streams: a dorsal pathway into developing
      cerebellar white matter, where the migrating cells dispersed widely before
      entering the internal granular layer, and a rostral pathway along the cerebellar
      ventricular zone toward the brainstem. Ablation of the rhombic lip in organotypic
      slice cultures substantially reduced the production of Tbr2+ UBCs. In coculture
      experiments, Tbr2+ UBCs migrated from rhombic lip explants directly into the
      developing white matter of adjacent cerebellar slices. The origin of Tbr2+ UBCs
      was confirmed by colocalization with beta-galactosidase expressed from the Math1
      locus, a molecular marker of rhombic lip lineages. Moreover, the production of
      Tbr2+ UBCs was Math1 dependent, as Tbr2+ UBCs were severely reduced in Math1-null
      cerebellum. In reeler mutant mice, Tbr2+ UBCs accumulated near the rhombic lip,
      consistent with impaired migration through developing white matter. Our results
      suggest that UBCs arise from the rhombic lip and migrate via novel pathways to
      their final destinations in the cerebellum and dorsal cochlear nucleus. Our
      findings support a model of cerebellar neurogenesis, in which glutamatergic and
      GABAergic neurons are produced from separate progenitor pools located mainly in
      the rhombic lip and the cerebellar ventricular zone, respectively.

PMID- 16957076
TI  - DeltaFosB in the nucleus accumbens regulates food-reinforced instrumental
      behavior and motivation.
AB  - Alterations in motivation have been implicated in the pathophysiology of several
      psychiatric disorders, including substance abuse and depression. Repeated
      exposure to drugs of abuse or stress is known to persistently induce the
      transcription factor deltaFosB in the nucleus accumbens (NAc) and dorsal
      striatum, effects hypothesized to contribute to neuroadaptations in dopamine
      regulated signaling. Little is known, however, about the specific involvement of
      deltaFosB in dysregulation of appetitively motivated behaviors. We show here that
      inducible overexpression of deltaFosB in NAc and dorsal striatum of bitransgenic
      mice, or specifically in the NAc core of rats by use of viral-mediated gene
      transfer, enhanced food-reinforced instrumental performance and progressive ratio
      responding. Very similar behavioral effects were found after previous repeated
      exposure to cocaine, amphetamine, MDMA [(+)-3,4-methylenedioxymethamphetamine],
      or nicotine in rats. These results reveal the powerful regulation of motivational
      processes by deltaFosB, and provide evidence that drug-induced alterations in
      gene expression via induction of deltaFosB within the NAc core may play a
      critical role in the impact of motivational influences on instrumental behavior.

PMID- 16957077
TI  - Angiotensin-II is a putative neurotransmitter in lactate-induced panic-like
      responses in rats with disruption of GABAergic inhibition in the dorsomedial
      hypothalamus.
AB  - Intravenous sodium lactate infusions or the noradrenergic agent yohimbine
      reliably induce panic attacks in humans with panic disorder but not in healthy
      controls. However, the exact mechanism of lactate eliciting a panic attack is
      still unknown. In rats with chronic disruption of GABA-mediated inhibition in the
      dorsomedial hypothalamus (DMH), achieved by chronic microinfusion of the glutamic
      acid decarboxylase inhibitor L-allylglycine, sodium lactate infusions or
      yohimbine elicits panic-like responses (i.e., anxiety, tachycardia, hypertension,
      and tachypnea). In the present study, previous injections of the angiotensin-II
      (A-II) type 1 receptor antagonist losartan and the nonspecific A-II receptor
      antagonist saralasin into the DMH of "panic-prone" rats blocked the anxiety-like
      and physiological components of lactate-induced panic-like responses. In
      addition, direct injections of A-II into the DMH of these panic-prone rats also
      elicited panic-like responses that were blocked by pretreatment with saralasin.
      Microinjections of saralasin into the DMH did not block the panic-like responses
      elicited by intravenous infusions of the noradrenergic agent yohimbine or by
      direct injections of NMDA into the DMH. The presence of the A-II type 1 receptors
      in the region of the DMH was demonstrated using immunohistochemistry. Thus, these
      results implicate A-II pathways and the A-II receptors in the hypothalamus as
      putative substrates for sodium lactate-induced panic-like responses in vulnerable
      subjects.

PMID- 16957078
TI  - Deciphering the spike train of a sensory neuron: counts and temporal patterns in
      the rat whisker pathway.
AB  - Rats achieve remarkable texture discriminations by sweeping their facial whiskers
      along surfaces. This work explores how neurons at two levels of the sensory
      pathway, trigeminal ganglion and barrel cortex, carry information about such
      stimuli. We identified two biologically plausible coding mechanisms, spike counts
      and patterns, and used "mutual information" to quantify how reliably neurons in
      anesthetized rats reported texture when "decoded" according to these candidate
      mechanisms. For discriminations between surfaces of different coarseness, spike
      counts could be decoded reliably and rapidly (within 30 ms after stimulus onset
      in cortex). Information increased as responses were considered as spike patterns
      with progressively finer temporal precision. At highest temporal resolution
      (spike sequences across six bins of 4 ms), the quantity of "information" in
      patterns rose 150% for ganglion neurons and 110% for cortical neurons above that
      in spike counts. In some cases, patterns permitted discriminations not supported
      by spike counts alone.

PMID- 16957079
TI  - The role of G-protein-coupled receptor kinase 5 in pathogenesis of sporadic
      Parkinson's disease.
AB  - Sporadic Parkinson's disease (sPD) is a common neurodegenerative disorder,
      characterized by selective degeneration of dopaminergic neurons in the substantia
      nigra. Although the pathogenesis of the disease remains undetermined,
      phosphorylation of alpha-synuclein and its oligomer formation seem to play a key
      role. However, the protein kinase(s) involved in the phosphorylation in the
      pathogenesis of sPD has not been identified. Here, we found that G-protein
      coupled receptor kinase 5 (GRK5) accumulated in Lewy bodies and colocalized with
      alpha-synuclein in the pathological structures of the brains of sPD patients. In
      cotransfected cells, GRK5 phosphorylated Ser-129 of alpha-synuclein at the plasma
      membrane and induced translocation of phosphorylated alpha-synuclein to the
      perikaryal area. GRK5-catalyzed phosphorylation also promoted the formation of
      soluble oligomers and aggregates of alpha-synuclein. Genetic association study
      revealed haplotypic association of the GRK5 gene with susceptibility to sPD. The
      haplotype contained two functional single-nucleotide polymorphisms, m22.1 and
      m24, in introns of the GRK5 gene, which bound to YY1 (Yin Yang-1) and CREB-1
      (cAMP response element-binding protein 1), respectively, and increased
      transcriptional activity of the reporter gene. The results suggest that
      phosphorylation of alpha-synuclein by GRK5 plays a crucial role in the
      pathogenesis of sPD.

PMID- 16957080
TI  - Integration of exogenous input into a dynamic salience map revealed by perturbing
      attention.
AB  - Although it is widely accepted that exogenous and voluntary factors jointly
      determine the locus of attention, the rules governing the integration of these
      factors are poorly understood. We investigated neural responses in the lateral
      intraparietal area (LIP) to transient, distracting visual perturbations presented
      during task performance. Monkeys performed a covert search task in which they
      discriminated the orientation of a target embedded among distractors, and brief
      visual perturbations were presented at various moments and locations during task
      performance. LIP neurons responded to perturbations consisting of the appearance
      of new objects, as well as to abrupt changes in the color, luminance, or position
      of existing objects. The LIP response correlated with the bottom-up behavioral
      effects of different perturbation types. In addition, neurons showed two types of
      top-down modulations. One modulation was a context-specific multiplicative gain
      that affected perturbation, target, and distractor activity in a spatially
      nonspecific manner. Gain was higher in blocks of trials in which perturbations
      directly marked target location than in blocks in which they invariably appeared
      opposite the target, thus encoding a behavioral context defined by the
      statistical contingency between target and perturbation location. A second
      modulation reflected local competitive interactions with search-related activity,
      resulting in the converse effect: weaker perturbation-evoked responses if
      perturbations appeared at the location of the target than if they appeared
      opposite the target. Thus, LIP encodes an abstract dimension of salience, which
      is shaped by local and global top-down mechanisms. These interacting mechanisms
      regulate responsiveness to external input as a function of behavioral context and
      momentary task demands.

PMID- 16957081
TI  - Protecting motor neurons from toxic insult by antagonism of adenosine A2a and Trk
      receptors.
AB  - The death of motor neurons in amyotrophic lateral sclerosis (ALS) is thought to
      result from the interaction of a variety of factors including excitotoxicity,
      accumulation of toxic proteins, and abnormal axonal transport. Previously, we
      found that the susceptibility of motor neurons to excitotoxic insults can be
      limited by inhibiting signals evoked by brain-derived neurotrophic factor (BDNF)
      activation of the receptor tyrosine kinase B (TrkB). Here we show that this can
      be achieved by direct kinase inhibition or by blockade of a transactivation
      pathway that uses adenosine A2a receptors and src-family kinases (SFKs).
      Downstream signaling cascades (such as mitogen-activated protein kinase and
      phosphatidylinositol-3 kinase) are inhibited by these blockers. In addition to
      protecting motor neurons from excitotoxic insult, these agents also prevent
      toxicity that follows from the expression of mutant proteins (G85R superoxide
      dismutase 1; G59S p150(glued)) that cause familial motor neuron disease. TrkB,
      adenosine A2a receptors, and SFKs associate into complexes in lipid raft and
      nonlipid raft membranes and the signaling from lipids rafts may be particularly
      important because their disruption by cholesterol depletion blocks the ability of
      BDNF to render motor neurons vulnerable to insult. The neuroprotective
      versatility of Trk antagonism suggests that it may have broad utility in the
      treatment of ALS patients.

PMID- 16957082
TI  - Mode of functional connectivity in amygdala pathways dissociates level of
      awareness for signals of fear.
AB  - Many of the same regions of the human brain are activated during conscious
      attention to signals of fear and in the absence of awareness for these signals.
      The neural mechanisms that dissociate level of awareness from activation in these
      regions remain unknown. Using functional magnetic resonance imaging with
      connectivity analysis in healthy human subjects, we demonstrate that level of
      awareness for signals of fear depends on mode of functional connectivity in
      amygdala pathways rather than discrete patterns of activation in these pathways.
      Awareness for fear relied on negative connectivity within both cortical and
      subcortical pathways to the amygdala, suggesting that reentrant feedback may be
      necessary to afford such awareness. In contrast, responses to fear in the absence
      of awareness were supported by positive connections in a direct subcortical
      pathway to the amygdala, consistent with the view that excitatory feedforward
      connections along this pathway may be sufficient for automatic responses to
      "unseen" fear.

PMID- 16957083
TI  - Transcranial magnetic stimulation over sensorimotor cortex disrupts anticipatory
      reflex gain modulation for skilled action.
AB  - Skilled interactions with new environments require flexible changes to the
      transformation from somatosensory signals to motor outputs. Transcortical reflex
      gains are known to be modulated according to task and environmental dynamics, but
      the mechanism of this modulation remains unclear. We examined reflex organization
      in the sensorimotor cortex. Subjects performed point-to-point arm movements into
      predictable force fields. When a small perturbation was applied just before the
      arm encountered the force field, reflex responses in the shoulder muscles changed
      according to the upcoming force field direction, indicating anticipatory reflex
      gain modulation. However, when a transcranial magnetic stimulation (TMS) was
      applied before the reflex response to such perturbations so that the silent
      period caused by TMS overlapped the reflex processing period, this modulation was
      abolished, while the reflex itself remained. Loss of reflex gain modulation could
      not be explained by reduced reflex amplitudes nor by peripheral effects of TMS on
      the muscles themselves. Instead, we suggest that TMS disrupted interneuronal
      networks in the sensorimotor cortex, which contribute to reflex gain modulation
      rather than reflex generation. We suggest that these networks normally provide
      the adaptability of rapid sensorimotor reflex responses by regulating reflex
      gains according to the current dynamical environment.

PMID- 16957084
TI  - Abnormal positioning of diencephalic cell types in neocortical tissue in the
      dorsal telencephalon of mice lacking functional Gli3.
AB  - The transcription factor Gli3 (glioma-associated oncogene homolog) is essential
      for normal development of the mammalian forebrain. One extreme requirement for
      Gli3 is at the dorsomedial telencephalon, which does not form in Gli3(Xt/Xt)
      mutant mice lacking functional Gli3. In this study, we analyzed expression of
      Gli3 in the wild-type telencephalon and observed a (high)dorsal-to-(low)ventral
      gradient of Gli3 expression and predominance of the cleaved form of the Gli3
      protein dorsally. This graded expression correlates with the (severe)dorsal-to
      (mild)ventral telencephalic phenotype observed in Gli3(Xt/Xt) mice. We
      characterized the abnormal joining of the telencephalon to the diencephalon and
      defined the medial limit of the dorsal telencephalon in Gli3(Xt/Xt) mice early in
      corticogenesis. Based on this analysis, we concluded that some of the abnormal
      expression of ventral telencephalic markers previously described as being in the
      dorsal telencephalon is, in fact, expression in adjacent diencephalic tissue,
      which expresses many of the same genes that mark the ventral telencephalon. We
      observed occasional cells with diencephalic character in the Foxg1 (forkhead box)
      expressing Gli3(Xt/Xt) telencephalon at embryonic day 10.5, a day after the
      anatomical subdivision of the forebrain vesicle. Large clusters of such cells
      appear in the Gli3(Xt/Xt) neocortical region at later ages, when the neocortex
      becomes highly disorganized, forming rosettes comprising mainly neural
      progenitors. We propose that Gli3 is indispensable for formation of an intact
      telencephalic-diencephalic boundary and for preventing the abnormal positioning
      of diencephalic cells in the dorsal telencephalon.

PMID- 16957085
TI  - The B' protein phosphatase 2A regulatory subunit well-rounded regulates synaptic
      growth and cytoskeletal stability at the Drosophila neuromuscular junction.
AB  - Synaptic growth is essential for the development and plasticity of neural
      circuits. To identify molecular mechanisms regulating synaptic growth, we
      performed a gain-of-function screen for synapse morphology mutants at the
      Drosophila neuromuscular junction (NMJ). We isolated a B' regulatory subunit of
      protein phosphatase 2A (PP2A) that we have named well-rounded (wrd). Neuronal
      overexpression of wrd leads to overgrowth of the synaptic terminal. Endogenous
      Wrd protein is present in the larval nervous system and muscle and is enriched at
      central and neuromuscular synapses. wrd is required for normal synaptic
      development; in its absence, there are fewer synaptic boutons and there is a
      decrease in synaptic strength. wrd functions presynaptically to promote normal
      synaptic growth and postsynaptically to maintain normal levels of evoked
      transmitter release. In the absence of wrd, the presynaptic cytoskeleton is
      abnormal, with an increased proportion of unbundled microtubules. Reducing PP2A
      enzymatic activity also leads to an increase in unbundled microtubules, an effect
      enhanced by reducing wrd levels. Hence, wrd promotes the function of PP2A and is
      required for normal cytoskeletal organization, synaptic growth, and synaptic
      function at the Drosophila NMJ.

PMID- 16957086
TI  - Alpha-synuclein overexpression increases cytosolic catecholamine concentration.
AB  - Dysregulation of dopamine homeostasis and elevation of the cytosolic level of the
      transmitter have been suggested to underlie the vulnerability of
      catecholaminergic neurons in Parkinson's disease. Because several known mutations
      in alpha-synuclein or overexpression of the wild-type (WT) protein causes
      familial forms of Parkinson's disease, we investigated possible links between
      alpha-synuclein pathogenesis and dopamine homeostasis. Chromaffin cells isolated
      from transgenic mice that overexpress A30P alpha-synuclein displayed
      significantly increased cytosolic catecholamine levels as measured by
      intracellular patch electrochemistry, whereas cells overexpressing the WT protein
      and those from knock-out animals were not different from controls. Likewise,
      catechol concentrations were higher in L-DOPA-treated PC12 cells overexpressing
      A30P or A53T compared with those expressing WT alpha-synuclein, although the
      ability of cells to maintain a low cytosolic dopamine level after L-DOPA
      challenge was markedly inhibited by either protein. We also found that incubation
      with low-micromolar concentrations of WT, A30P, or A53T alpha-synuclein inhibited
      ATP-dependent maintenance of pH gradients in isolated chromaffin vesicles and
      that the WT protein was significantly less potent in inducing the proton leakage.
      In summary, we demonstrate that overexpression of different types of alpha
      synuclein disrupts vesicular pH and leads to a marked increase in the levels of
      cytosolic catechol species, an effect that may in turn trigger cellular
      oxyradical damage. Although multiple molecular mechanisms may be responsible for
      the perturbation of cytosolic catecholamine homeostasis, this study provides
      critical evidence about how alpha-synuclein might exert its cytotoxicity and
      selectively damage catecholaminergic cells.

PMID- 16957087
TI  - Astrocytic glutamate is not necessary for the generation of epileptiform neuronal
      activity in hippocampal slices.
AB  - The release of glutamate from astrocytes activates synchronous slow inward
      currents (SICs) in hippocampal pyramidal neurons, which are mediated by the NMDA
      receptor and represent a nonsynaptic mechanism to promote the synchronization of
      neuronal activity. Two recent studies demonstrate that SICs generate neuronal
      paroxysmal depolarizations resembling those typical of interictal epileptiform
      activity and proposed that there could be an astrocytic basis of epilepsy (Kang
      et al., 2005; Tian et al., 2005). We tested this hypothesis using two in vitro
      models of epileptiform activity in hippocampal slices. Removal of extracellular
      Mg2+ and application of picrotoxin or perfusion with 0.5 mM Mg2+ and 8.5 mM K+
      containing saline result mainly in neuronal ictal- and interictal-like
      epileptiform activity, respectively. Although both models trigger epileptiform
      activity, astrocytic Ca2+ oscillations were increased only after slice perfusion
      with 0 mM Mg2+ and picrotoxin. The activation of astrocytic Ca2+ signaling
      correlates with an increased frequency of SICs, and, when paired neurons were
      within 100 microm of one another with synchronous neuronal Ca2+ elevations, the
      generation of synchronous neuronal depolarizations and action potential
      discharges. TTX blocked both ictal- and interictal-like epileptiform activity
      without affecting SICs or SIC-mediated neuronal synchronization. In contrast,
      NMDA receptor antagonists, which block SICs, did not prevent the generation of
      either ictal- or interictal-like events. Based on this clear-cut pharmacology,
      our data demonstrate that nonsynaptic glutamate release from astrocytes is not
      necessary for the generation of epileptiform activity in vitro, although we
      cannot exclude the possibility that it may modulate the strength of the ictal
      (seizure)-like event.

PMID- 16957088
TI  - Deletion of the GABA(A) receptor alpha1 subunit increases tonic GABA(A) receptor
      current: a role for GABA uptake transporters.
AB  - The loss of more than half the number of GABA(A) receptors yet lack of pronounced
      phenotype in mice lacking the gene for the GABA(A) alpha1 subunit is somewhat
      paradoxical. We explored the role of tonic GABA(A) receptor-mediated current as a
      target of compensatory regulation in the alpha1 knock-out (-/-) mice. A 62%
      increase of tonic current was observed in the cerebellar granule cells (CGCs) of
      alpha1-/- compared with wild-type (+/+) mice along with a 67% increase of
      baseline current variance. Examination of whole-cell currents evoked by low
      concentrations of GABA and 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol
      suggested no upregulation of alpha6 and delta subunit-containing GABA(A)
      receptors in the alpha1-/-, confirming previous biochemical studies. Single
      channel current openings were on average 32% shorter in the alpha1-/- neurons.
      Single-channel conductance and frequency of opening were not different between
      genotypes. Tonic current induced by application of the GABA transporter GAT-1
      blocker NO711 (1-[2([(diphenylmethylene)imino]oxy)ethyl]-1,2,5,6-tetrahydro-3
      pyridinecarboxylic acid hydrochloride) was significantly larger in the alpha1-/-,
      suggesting an increase of ambient GABA concentration. Experiments done with a
      known concentration of extracellular GABA complemented by a series of biochemical
      experiments revealed a reduction of GAT activity in alpha1-/- without an
      identifiable reduction of GAT-1 or GAT-3 protein. We report increased tonic
      GABA(A) receptor-mediated current in the alpha1-/- CGCs as a novel compensatory
      mechanism. Our data establish a role for GABA transporters as regulators of
      neuronal excitability in this and relevant models and examine other tonic
      conductance-regulating mechanisms responsible for the adaptive response of the
      cerebellar network to a deletion of a major synaptic GABA(A) receptor subunit.

PMID- 16957089
TI  - The activation of excitatory glutamate receptors evokes a long-lasting increase
      in the release of GABA from cerebellar stellate cells.
AB  - The excitability of a neuron is regulated by the balance of excitatory and
      inhibitory inputs that impinge on it. Such modulation can occur either
      presynaptically or postsynaptically. Here, we show that an excitatory transmitter
      can increase the release of an inhibitory transmitter and thus paradoxically
      produces a long-lasting enhancement of inhibitory synaptic transmission. This
      occurs at a near-physiological temperature. These findings from cerebellar
      stellate neurons reveal a novel form of long-term potentiation that is induced by
      the activation of NMDA-type glutamate receptors and that requires both glutamate
      and glycine. Our results indicate that Ca2+ entry into the presynaptic terminals
      during the activation of presynaptic NMDARs is necessary to induce the
      potentiation. This presynaptic modulation provides a mechanism by which an
      excitatory transmitter can induce a long-term increase in the release of an
      inhibitory transmitter and thus modify the activity of a simple neuronal circuit.

PMID- 16957091
TI  - Rice chitinases: sugar recognition specificities of the individual subsites.
AB  - Sugar recognition specificities of class III (OsChib1a) and class I
      (OsChia1cDeltaChBD) chitinases from rice, Oryza sativa L., were investigated by
      analyzing (1)H- and (13)C-nuclear magnetic resonance spectra of the enzymatic
      products from partially N-acetylated chitosans. The reducing end residue of the
      enzymatic products obtained by the class III enzyme was found to be exclusively
      acetylated, whereas both acetylated and deacetylated units were found at the
      nearest neighbor to the reducing end residue. Both acetylated and deacetylated
      units were also found at the nonreducing end residue and its nearest neighbor of
      the class III enzyme products. Thus, only subsite (-1) among the contiguous
      subsites (-2) to (+2) of the class III enzyme was found to be specific to an
      acetylated residue. For the class I enzyme, the reducing end residue was
      preferentially acetylated, although the specificity was not absolute. The nearest
      neighbor to the acetylated reducing end residue was specifically acetylated.
      Moreover, the nonreducing end residue produced by the class I enzyme was
      exclusively acetylated, although there was a low but significant preference for
      deacetylated units at the nearest neighbor to the nonreducing end. These results
      suggest that the three contiguous subsites (-2), (-1), and (+1) of the class I
      enzyme are specific to three consecutive GlcNAc residues of the substrate. In
      rice plants, the target of the class I enzyme might be a consecutive GlcNAc
      sequence probably in the cell wall of fungal pathogen, whereas the class III
      enzyme might act toward an endogenous complex carbohydrate containing GlcNAc
      residue.

PMID- 16957090
TI  - Activation of P2Y1 nucleotide receptors induces inhibition of the M-type K+
      current in rat hippocampal pyramidal neurons.
AB  - We have shown previously that stimulation of heterologously expressed P2Y1
      nucleotide receptors inhibits M-type K+ currents in sympathetic neurons. We now
      report that activation of endogenous P2Y1 receptors induces inhibition of the M
      current in rat CA1/CA3 hippocampal pyramidal cells in primary neuron cultures.
      The P2Y1 agonist adenosine 5'-[beta-thio]diphosphate trilithium salt (ADPbetaS)
      inhibited M-current by up to 52% with an IC50 of 84 nM. The hydrolyzable agonist
      ADP (10 microM) produced 32% inhibition, whereas the metabotropic glutamate
      receptor 1/5 agonist DHPG [(S)-3,5-dihydroxyphenylglycine] (10 microM) inhibited
      M-current by 44%. The M-channel blocker XE991 [10,10-bis(4-pyridinylmethyl)
      9(10H)-anthracenone dihydrochloride] produced 73% inhibition at 3 microM; neither
      ADPbetaS nor ADP produced additional inhibition in the presence of XE991. The
      effect of ADPbetaS was prevented by a specific P2Y1 antagonist, MRS 2179 (2'
      deoxy-N'-methyladenosine-3',5'-bisphosphate tetra-ammonium salt) (30 microM).
      Inhibition of the M-current by ADPbetaS was accompanied by increased neuronal
      firing in response to injected current pulses. The neurons responding to ADPbetaS
      were judged to be pyramidal cells on the basis of (1) morphology, (2) firing
      characteristics, and (3) their distinctive staining for the pyramidal cell marker
      neurogranin. Strong immunostaining for P2Y1 receptors was shown in most cells in
      these cultures: 74% of the cells were positive for both P2Y1 and neurogranin,
      whereas 16% were only P2Y1 positive. These results show the presence of
      functional M-current-inhibitory P2Y1 receptors on hippocampal pyramidal neurons,
      as predicted from their effects when expressed in sympathetic neurons. However,
      the mechanism of inhibition in the two cell types seems to differ because, unlike
      nucleotide-mediated M-current inhibition in sympathetic neurons, that in
      hippocampal neurons did not appear to result from raised intracellular calcium.

PMID- 16957092
TI  - Overproduction and increased molecular weight account for the symbiotic activity
      of the rkpZ-modified K polysaccharide from Sinorhizobium meliloti Rm1021.
AB  - K polysaccharides (KPSs) of Sinorhizobium meliloti strains are strain-specific
      surface polysaccharides analogous to the group II K antigens of Escherichia coli.
      The K(R)5 antigen of strain AK631 is a highly polymerized disaccharide of
      pseudaminic and glucuronic acids. During invasion of host plants, this K antigen
      is able to replace the structurally different exopolysaccharide succinoglycan
      (EPS I) and promotes the formation of a nitrogen-fixing (Fix(+)) symbiosis. The
      KPS of strain Rm1021 is a homopolymer of 3-deoxy-D-manno-2 octulosonic acid
      (Kdo). The Kdo polysaccharide is covalently linked to the lipid anchor, has a low
      molecular weight (LMW), and is symbiotically inactive. On introduction of the
      Rm41-specific rkpZ gene into strain Rm1021, a modified KPS is expressed that is
      able to substitute EPS I during symbiosis with the host plant. To better
      understand the nature of modification conferred by rkpZ, we performed a
      structural analysis of the KPS using nuclear magnetic resonance (NMR),
      electrospray ionization-mass spectrometry (ESI-MS), and gas chromatography (GC
      MS). The modified KPS retained primary polyKdo structure, but its degree of
      polymerization (DP) and level of production were increased significantly. In
      contrast to the wild-type polyKdo, only a part of polyKdo was lipidated. Shorter
      polysaccharide chains were lipid-free, whereas longer polysaccharide chains were
      lipidated. Sinorhizobium meliloti Rm1021 was found to carry two paralogs of rkpZ.
      Both genes are involved in polyKdo production, but they only show partial
      functional activity as compared with the rkpZ of Rm41.

PMID- 16957093
TI  - List of new names and new combinations previously effectively, but not validly,
      published.
AB  - The purpose of this announcement is to effect the valid publication of the
      following new names and new combinations under the procedure described in the
      Bacteriological Code (1990 Revision). Authors and other individuals wishing to
      have new names and/or combinations included in future lists should send three
      copies of the pertinent reprint or photocopies thereof to the IJSEM Editorial
      Office for confirmation that all of the other requirements for valid publication
      have been met. It is also a requirement of IJSEM and the ICSP that authors of new
      species, new subspecies and new combinations provide evidence that types are
      deposited in two recognized culture collections in two different countries (i.e.
      documents certifying deposition and availability of type strains). It should be
      noted that the date of valid publication of these new names and combinations is
      the date of publication of this list, not the date of the original publication of
      the names and combinations. The authors of the new names and combinations are as
      given below, and these authors' names will be included in the author index of the
      present issue and in the volume author index. Inclusion of a name on these lists
      validates the publication of the name and thereby makes it available in
      bacteriological nomenclature. The inclusion of a name on this list is not to be
      construed as taxonomic acceptance of the taxon to which the name is applied.
      Indeed, some of these names may, in time, be shown to be synonyms, or the
      organisms may be transferred to another genus, thus necessitating the creation of
      a new combination.

PMID- 16957094
TI  - Notification that new names and new combinations have appeared in volume 56, part
      6, of the IJSEM.
AB  - This listing of names published in a previous issue of the IJSEM is provided as a
      service to bacteriology to assist in the recognition of new names and new
      combinations. This procedure was proposed by the Judicial Commission [Minute
      11(ii), Int J Syst Bacteriol 41 (1991), p. 185]. The names given herein are
      listed according to the Rules of priority (i.e. page number and order of valid
      publication of names in the original articles). Taxonomic opinions included in
      this List (i.e. the creation of synonyms or the emendation of circumscriptions)
      cannot be considered as validly published nor, in any other way, approved by the
      International Committee on Systematics of Prokaryotes and its Judicial
      Commission.

PMID- 16957095
TI  - Sphingobacterium daejeonense sp. nov., isolated from a compost sample.
AB  - A Gram-negative, strictly aerobic, rod-shaped, non-motile, non-spore-forming
      bacterial strain, designated TR6-04(T), was isolated from compost and
      characterized taxonomically by using a polyphasic approach. The organism grew
      optimally at 30 degrees Celsius and at pH 6.5-7.0. The isolate was positive for
      catalase and oxidase tests but negative for gelatinase, indole and H(2)S
      production. Comparative 16S rRNA gene sequence analysis showed that strain TR6
      04(T) fell within the radiation of the cluster comprising Sphingobacterium
      species and clustered with Sphingobacterium mizutaii ATCC 33299(T) (96.7 %
      sequence similarity); the similarity to sequences of other species within the
      family Sphingobacteriaceae was less than 92.0 %. The G+C content of the genomic
      DNA was 38.7 mol%. The predominant respiratory quinone was MK-7. The major fatty
      acids were iso-C(15 : 0), iso-C(17 : 0) 3-OH and summed feature 4 (iso-C(15 : 0)
      2-OH and/or C(16 : 1)omega7c). These chemotaxonomic data supported the
      affiliation of strain TR6-04(T) to the genus Sphingobacterium. However, on the
      basis of its phenotypic properties and phylogenetic distinctiveness, strain TR6
      04(T) (=KCTC 12579(T)=LMG 23402(T)=CCUG 52468(T)) should be classified as the
      type strain of a novel species, for which the name Sphingobacterium daejeonense
      sp. nov. is proposed.

PMID- 16957096
TI  - Aquimarina intermedia sp. nov., reclassification of Stanierella latercula (Lewin
      1969) as Aquimarina latercula comb. nov. and Gaetbulimicrobium brevivitae Yoon et
      al. 2006 as Aquimarina brevivitae comb. nov. and emended description of the genus
      Aquimarina.
AB  - A heterotrophic, aerobic, Gram-negative, pigmented and gliding bacterium, strain
      KMM 6258(T), was isolated from the sea urchin Strongylocentrotus intermedius and
      investigated using a polyphasic taxonomic approach. 16S rRNA gene sequence
      analysis revealed that the closest relatives of the novel strain are Aquimarina
      muelleri, Stanierella latercula and Gaetbulimicrobium brevivitae, members of the
      family Flavobacteriaceae, with sequence similarities of 96.3, 96.4 and 96.2 %,
      respectively. Phylogenetic evidence, supported by chemotaxonomic and phenotypic
      data, assigned strain KMM 6258(T) to the genus Aquimarina as Aquimarina
      intermedia sp. nov. (type strain KMM 6258(T)=DSM 17527(T)=JCM 13506(T)=LMG
      23204(T)). The reclassification of Stanierella latercula as Aquimarina latercula
      comb. nov. and Gaetbulimicrobium brevivitae as Aquimarina brevivitae comb. nov.
      is proposed.

PMID- 16957097
TI  - Actinomyces ruminicola sp. nov., isolated from cattle rumen.
AB  - Two obligate anaerobic bacterial strains, B71(T) and D471, were isolated from
      cattle rumen. The novel strains were Gram-positive and rod-shaped. The strains
      hydrolysed xylan and starch, fermented some mono-, di- and oligosaccharides and
      produced formic, acetic and lactic acids as end products from glucose. Growth of
      the isolates was observed at 20-55 degrees Celsius and pH 6.5-9.0. The DNA G+C
      contents of strains B71(T) and D471 were 68.06 and 68.26 mol%, respectively.
      Although the two novel strains met the genus description for Actinomyces, some
      phenotypic characteristics, such as optimum growth temperature, requirement for
      O(2) and the end products of fermentation, distinguished them from previously
      described members of the genus. Phylogenetic analysis based on 16S rRNA gene
      sequences demonstrated that the novel strains belonged to the genus Actinomyces
      (88.3-93.6 % sequence similarity) and formed a distinct line within the clade
      containing Actinomyces bovis. On the basis of these results, a novel species,
      Actinomyces ruminicola sp. nov., is proposed. The type strain is B71(T) (=JCM
      13352(T)=CGMCC 1.5030(T)).

PMID- 16957098
TI  - Mycobacterium colombiense sp. nov., a novel member of the Mycobacterium avium
      complex and description of MAC-X as a new ITS genetic variant.
AB  - Forty-five mycobacterial strains isolated from 23 Colombian HIV-positive patients
      were identified as members of the Mycobacterium avium complex (MAC) and were
      characterized using different molecular approaches. Seven of the isolates showed
      characteristic features that allowed them to be differentiated from other members
      of the complex. The isolates had a novel 16S-23S rRNA internal transcribed spacer
      (ITS 1) gene sequence which is described as a new sequevar, MAC-X. All of the
      seven novel isolates gave a positive result with the MAC-specific AccuProbe (Gen
      Probe), but tested negative for Mycobacterium avium and Mycobacterium
      intracellulare species-specific probes (64 and 100 % of the isolates,
      respectively). The novel isolates could be differentiated phenotypically from
      other members of the MAC on the basis of the production of urease and by a
      consistent mycolic acid pattern. The novel isolates shared some characteristics
      with M. avium, such as the avium variant I (av-I) pattern of the hsp65 gene as
      determined by PCR restriction analysis and a positive PCR result for the mig
      (macrophage-induced) gene. However, the novel isolates showed a unique 16S rRNA
      gene sequence. DNA-DNA relatedness values, from 24 to 44 %, confirmed the
      distinction of the novel isolates from other members of the MAC at the genetic
      level and their status as members of a separate species. The novel isolates are
      proposed as representatives of a novel species, Mycobacterium colombiense sp.
      nov., that is closely related to M. avium within the MAC. The type strain is
      10B(T) (=CIP 108962(T)=CECT 3035(T)).

PMID- 16957099
TI  - Trichococcus patagoniensis sp. nov., a facultative anaerobe that grows at -5
      degrees C, isolated from penguin guano in Chilean Patagonia.
AB  - A novel, extremely psychrotolerant, facultative anaerobe, strain PmagG1(T), was
      isolated from guano of Magellanic penguins (Spheniscus magellanicus) collected in
      Chilean Patagonia. Gram-variable, motile cocci with a diameter of 1.3-2.0 mum
      were observed singularly or in pairs, short chains and irregular conglomerates.
      Growth occurred within the pH range 6.0-10.0, with optimum growth at pH 8.5. The
      temperature range for growth of the novel isolate was from -5 to 35 degrees C,
      with optimum growth at 28-30 degrees C. Strain PmagG1(T) did not require NaCl, as
      growth was observed in the presence of 0-6.5 % NaCl with optimum growth at 0.5 %
      (w/v). Strain PmagG1(T) was a catalase-negative chemo-organoheterotroph that used
      sugars and some organic acids as substrates. The metabolic end products were
      lactate, formate, acetate, ethanol and CO(2). Strain PmagG1(T) was sensitive to
      ampicillin, tetracycline, chloramphenicol, rifampicin, kanamycin and gentamicin.
      The G+C content of its genomic DNA was 45.8 mol%. 16S rRNA gene sequence analysis
      showed 100 % similarity of strain PmagG1(T) with Trichococcus collinsii ATCC BAA
      296(T), but DNA-DNA hybridization between them demonstrated relatedness values of
      <45+/-1 %. Another phylogenetically closely related species, Trichococcus
      pasteurii, showed 99.85 % similarity by 16S rRNA sequencing and DNA-DNA
      hybridization showed relatedness values of 47+/-1.5 %. Based on genotypic and
      phenotypic characteristics, the novel species Trichococcus patagoniensis sp. nov.
      is proposed, with strain PmagG1(T) (=ATCC BAA-756(T)=JCM 12176(T)=CIP 108035(T))
      as the type strain.

PMID- 16957100
TI  - Desulfohalobium utahense sp. nov., a moderately halophilic, sulfate-reducing
      bacterium isolated from Great Salt Lake.
AB  - A novel moderately halophilic, sulfate-reducing bacterium, strain EtOH3(T), was
      isolated from anoxic hypersaline (270 g NaCl l(-1)) sediment of the northern arm
      of the Great Salt Lake, Utah, USA. Cells of strain EtOH3(T) were oval to rod
      shaped, non-motile, non-sporulating and stained Gram-negative. The strain
      required sodium and magnesium ions for growth and grew at salinities of up to 240
      g NaCl l(-1) and 121 g MgCl(2).6H(2)O l(-1). The optimum NaCl concentration was
      80-100 g l(-1). Strain EtOH3(T) grew at temperatures ranging from 15 to 44
      degrees Celsius (optimum 37 degrees Celsius). The pH range for growth was 6.5-8.3
      (optimum around pH 6.8). Only sulfate and thiosulfate served as electron
      acceptors for a broad range of electron donors including various short-chain
      fatty acids and primary (C(1-5)) alcohols, amino acids, H(2)/acetate and
      H(2)/yeast extract. The G+C content of the genomic DNA was 51.4 mol%.
      Phylogenetic analysis of dsrAB [genes encoding the major subunits of
      dissimilatory (bi)sulfite reductase] and 16S rRNA gene sequence data placed
      strain EtOH3(T) within the deltaproteobacterial family Desulfohalobiaceae. Strain
      EtOH3(T) shared 76 and 91 % dsrAB and 16S rRNA gene sequence similarity,
      respectively, with the type strain of the phylogenetically most closely related
      species with a validly published name, Desulfohalobium retbaense DSM 5692(T).
      High 16S rRNA gene sequence similarity ( approximately 97 %) was shared with the
      recently described strain 'Desulfovermiculus halophilus' VKM B-2364. Strain
      EtOH3(T), however, clearly differed from this strain in both genomic G+C content
      and in several of its phenotypic properties. On the basis of phenotypic and
      genotypic characteristics, the novel species Desulfohalobium utahense sp. nov. is
      proposed, with strain EtOH3(T) (=VKM B-2384(T)=DSM 17720(T)) as the type strain.

PMID- 16957101
TI  - Proposal of Hymenobacter norwichensis sp. nov., classification of 'Taxeobacter
      ocellatus', 'Taxeobacter gelupurpurascens' and 'Taxeobacter chitinovorans' as
      Hymenobacter ocellatus sp. nov., Hymenobacter gelipurpurascens sp. nov. and
      Hymenobacter chitinivorans sp. nov., respectively, and emended description of the
      genus Hymenobacter Hirsch et al. 1999.
AB  - Two airborne bacterial isolates, NS/2 and NS/50(T), were examined in order to
      determine their taxonomic position. Their almost complete 16S rRNA gene sequences
      shared 95.9 % similarity. Sequence comparisons demonstrated that their next
      relatives are species of the genus Hymenobacter (93.6-95.7 % similarity) and the
      strains 'Taxeobacter chitinovorans' Txc1(T), 'Taxeobacter gelupurpurascens'
      Txg1(T) and 'Taxeobacter ocellatus' Myx 2105(T) (90.5-96.4 %). Phylogenetic
      calculations indicated that these five strains together with the three recognized
      Hymenobacter species form a separate line of descent within the family
      'Flexibacteraceae'. Isolates NS/2 and NS/50(T), as well as 'Taxeobacter
      chitinovorans' Txc1(T), 'Taxeobacter gelupurpurascens' Txg1(T) and 'Taxeobacter
      ocellatus' Myx 2105(T), possessed the characteristics of the genus Hymenobacter,
      the quinone system menaquinone MK-7 and a polyamine pattern with the major
      polyamine being sym-homospermidine. Each of the five strains had complex, unique
      polar lipid profiles, with phosphatidylethanolamine and several unknown
      aminophospho-, amino-, phospho-, glyco- and polar lipids of which several
      compounds were also found in established Hymenobacter species. All the strains
      studied possessed fatty acids characteristic of Hymenobacter species, including
      major acids iso-C(15 : 0), anteiso-C(15 : 0), C(16 : 1)omega5c, summed feature 3
      (C(16 : 1)omega7c/iso-C(15 : 0) 2-OH) and summed feature 4 (iso-C(17 : 1)
      I/anteiso-C(17 : 1) B). The five strains could be distinguished from each other
      and from the three established species of the genus Hymenobacter based on
      relatively low 16S rRNA gene sequence similarities (<97 %), unique polar lipids
      and differing fatty acid profiles and physiological characteristics. In
      conclusion, the description of four novel species of the genus Hymenobacter
      appears to be justified, for which the names Hymenobacter norwichensis sp. nov.
      (type strain NS/50(T)=LMG 21876(T)=DSM 15439(T)), Hymenobacter chitinivorans sp.
      nov. (type strain Txc1(T)=LMG 21951(T)=DSM 11115(T)), Hymenobacter
      gelipurpurascens sp. nov. (type strain Txg1(T)=LMG 21874(T)=DSM
      [corrected][11116(T)) and Hymenobacter ocellatus sp. nov. (type strain Myx
      2105(T)=Txo1(T)=LMG 21873(T)=DSM 11117(T)) are proposed. For strain NS/2, a
      description only is provided without proposal of a name because its status as a
      novel species was not demonstrated unambiguously.

PMID- 16957102
TI  - Dyella yeojuensis sp. nov., isolated from greenhouse soil in Korea.
AB  - A novel strain, R2A16-10(T), was isolated from greenhouse soil in Yeoju, Korea.
      The taxonomy of strain R2A16-10(T) was studied by using polyphasic methods. On
      the basis of 16S rRNA gene sequence analyses, strain R2A16-10(T) was found to be
      phylogenetically related to type strains of Dyella species (96.7-96.9 %),
      Frateuria aurantia DSM 6220(T) (96.5 %), Fulvimonas soli LMG 19981(T) (96.3 %)
      and Rhodanobacter species (94.9-95.7 %). Strain R2A16-10(T), which produced
      yellow-coloured colonies, was Gram-negative, rod-shaped (0.3-0.4x1.5-3.5 mum) and
      motile. The predominant fatty acids were 17 : 1 iso omega9c (25.5 %), 15 : 0 iso
      (18.7 %) and 17 : 0 iso (14.6 %), and the major hydroxy fatty acids were 11 : 0
      iso 3-OH (5.0 %), 13 : 0 iso 3-OH (3.4 %) and 17 : 0 iso 3-OH (1.0 %). The major
      isoprenoid quinone was Q-8. The G+C content of the DNA of the type strain was
      63.0 mol%. On the basis of the data from this study, strain R2A16-10(T)
      represents a novel species of the genus Dyella, for which the name Dyella
      yeojuensis sp. nov. is proposed. The type strain is R2A16-10(T) (=KACC
      11405(T)=DSM 17673(T)).

PMID- 16957103
TI  - Asticcacaulis benevestitus sp. nov., a psychrotolerant, dimorphic, prosthecate
      bacterium from tundra wetland soil.
AB  - A Gram-negative, aerobic, heterotrophic, non-pigmented, dimorphic prosthecate
      bacterium was isolated from tundra wetland soil and designated strain Z-0023(T).
      Cells of this strain had a dimorphic life cycle and developed a non-adhesive
      stalk at a site not coincident with the centre of the cell pole, a characteristic
      typical of representatives of the genus Asticcacaulis. A highly distinctive
      feature of cells of strain Z-0023(T) was the presence of a conical, bell-shaped
      sheath when grown at low temperature. This prosthecate bacterium was a
      psychrotolerant, moderately acidophilic organism capable of growth between 4 and
      28 degrees Celsius (optimum 15-20 degrees Celsius) and between pH 4.5 and 8.0
      (optimum 5.6-6.0). The major phospholipid fatty acid was 18 : 1omega7c and the
      major phospholipids were phosphatidylglycerols. The G+C content of the DNA was
      60.4 mol%. On the basis of 16S rRNA gene sequence similarity, strain Z-0023(T)
      was most closely related to Asticcacaulis biprosthecium (98 % similarity),
      Asticcacaulis taihuensis (98 %) and Asticcacaulis excentricus (95 %). However,
      low levels of DNA-DNA relatedness to these organisms and a number of distinctive
      features of the tundra wetland isolate indicated that it represented a novel
      species of the genus Asticcacaulis, for which the name Asticcacaulis benevestitus
      sp. nov. is proposed. The type strain is Z-0023(T) (=DSM 16100(T)=ATCC BAA
      896(T)).

PMID- 16957104
TI  - Gracilibacter thermotolerans gen. nov., sp. nov., an anaerobic, thermotolerant
      bacterium from a constructed wetland receiving acid sulfate water.
AB  - An obligatorily anaerobic, thermotolerant, asporogenic bacterium, strain JW/YJL
      S1(T), was isolated from a sediment sample of a constructed wetland system
      receiving acid sulfate water (pH 1.6-3.0). Cells of strain JW/YJL-S1(T) were
      straight to curved rods 0.2-0.4 mum in diameter and 2.0-7.0 mum in length, and
      stained Gram-negative. Growth of strain JW/YJL-S1(T) was observed at 25-54
      degrees C (no growth at or below 20 or at or above 58 degrees C), with an optimum
      temperature range for growth of 42.5-46.5 degrees C. The pH(25 degrees C) range
      for growth was 6.0-8.25 (no growth at or below pH 5.7 or at or above pH 8.5),
      with optimum growth at pH 6.8-7.75. The salinity range for growth was 0-1.5 %
      (w/v) NaCl, with an optimum at 0-0.5 %. During growth on glucose the isolate
      produced acetate, lactate and ethanol as main fermentation end products. The
      fatty acid composition was dominated by branched-chain compounds: i15 : 0, a15 :
      0, i16 : 0 and i17 : 0. The G+C content of the genomic DNA was 42.8 mol% (HPLC).
      Strain JW/YJL-S1(T) showed polymorphism of the 16S rRNA gene. Its closest
      relative was the thermophilic Clostridium thermosuccinogenes DSM 5807(T) (a
      member of Clostridium cluster III) (a blastn search revealed Clostridium pascui
      DSM 10365(T) to have 92.7 % gene sequence similarity, the highest value). The
      inferred phylogenetic trees placed strain JW/YJL-S1(T) between Clostridium
      clusters I/II and III. Based on the morphological and phylogenetic data
      presented, JW/YJL-S1(T) (=DSM 17427(T)=ATCC BAA-1219(T)) is proposed as the type
      strain of a novel species in a new genus, Gracilibacter thermotolerans gen. nov.,
      sp. nov.

PMID- 16957105
TI  - Emendation of the genus Flammeovirga and Flammeovirga aprica with the proposal of
      Flammeovirga arenaria nom. rev., comb. nov. and Flammeovirga yaeyamensis sp. nov.
AB  - The taxonomic positions of five bacterial strains isolated from the Yaeyama
      Islands of Japan and 'Microscilla arenaria' NBRC 15982 were determined using a
      polyphasic taxonomic approach. 16S rRNA gene sequence analyses placed all of the
      strains close to the genus Flammeovirga. DNA-DNA hybridization studies,
      biochemical and physiological characterizations and chemotaxonomic analyses
      suggested that 'M. arenaria' NBRC 15982 and the five novel isolates represented
      two separate species of the genus Flammeovirga. Emendation of the genus
      Flammeovirga Nakagawa et al. 1997 and the species Flammeovirga aprica
      (Reichenbach 1989) Nakagawa et al. 1997 is proposed. In addition, 'Microscilla
      arenaria' Lewin 1969 is proposed as Flammeovirga arenaria nom. rev., comb. nov.
      (with the type strain NBRC 15982(T)=CIP 109101(T)) and the novel isolates are
      proposed as Flammeovirga yaeyamensis sp. nov. (type strain IR25-3(T)=NBRC
      100898(T)=CIP 109099(T)).

PMID- 16957106
TI  - Reclassification of Gluconacetobacter hansenii strains and proposals of
      Gluconacetobacter saccharivorans sp. nov. and Gluconacetobacter nataicola sp.
      nov.
AB  - Ten strains previously assigned to Acetobacter hansenii (=Gluconacetobacter
      hansenii), Acetobacter pasteurianus LMG 1584 and eight reference strains of the
      genus Gluconacetobacter were reclassified by 16S rRNA gene sequencing, DNA-DNA
      similarity, DNA base composition and phenotypic characteristics. The A. hansenii
      strains and A. pasteurianus LMG 1584 were included in the cluster of acetic acid
      bacteria (family Acetobacteraceae) by 16S rRNA gene sequences. Further, they were
      separated into seven distinct groups by DNA-DNA similarity. DNA-DNA similarity
      group I was identified as G. hansenii. DNA-DNA similarity group II was retained
      as Gluconacetobacter sp., because DNA-DNA similarity between the strain and
      Gluconacetobacter entanii LTH 4560(T) could not be determined. This was due to a
      lack of availability of the type strain from any source. DNA-DNA similarity group
      III was regarded as a novel species, for which the name Gluconacetobacter
      saccharivorans sp. nov. (type strain, LMG 1582(T)=NRIC 0614(T)) is proposed. DNA
      DNA similarity group IV included the type strains of Gluconacetobacter oboediens
      and Gluconacetobacter intermedius, and three A. hansenii strains. This group was
      identified as G. oboediens because high values of DNA-DNA similarity were
      obtained between the type strains and G. oboediens has priority over G.
      intermedius. DNA-DNA similarity group V was identified as Gluconacetobacter
      europaeus. DNA-DNA similarity group VI was regarded as a novel species, for which
      the name Gluconacetobacter nataicola sp. nov. (type strain, LMG 1536(T)=NRIC
      0616(T)) is proposed. DNA-DNA similarity group VII was reclassified as
      Gluconacetobacter xylinus. The description of G. hansenii is emended.

PMID- 16957107
TI  - Microbacterium deminutum sp. nov., Microbacterium pumilum sp. nov. and
      Microbacterium aoyamense sp. nov.
AB  - Three novel bacterial strains were isolated from a soil sample collected in Japan
      by culture on a GPM agar plate supplemented with superoxide dismutase and
      catalase. The strains were Gram-positive, catalase-positive, non-motile bacteria
      with L-ornithine as a diagnostic diamino acid of the peptidoglycan. The acyl type
      of the peptidoglycan was N-glycolyl. The major menaquinones were MK-12, 13 and
      14. Mycolic acids were not detected. G+C contents of the DNA were in the range 69
      71 mol%. Comparative 16S rRNA gene sequence analysis revealed that the isolates
      belonged to the genus Microbacterium and were closely related to Microbacterium
      terregens, Microbacterium aurum, Microbacterium koreense, Microbacterium
      schleiferi and Microbacterium lacticum. However, M. aurum, M. koreense and M.
      lacticum clearly differed from the isolated strains based on the presence of L
      lysine as the cell-wall diamino acid and various other chemotaxonomic
      characteristics. Levels of DNA-DNA relatedness showed that the isolated strains
      represented three separate genomic species. Based on both phenotypic and
      genotypic data, the following novel species of the genus Microbacterium are
      proposed: Microbacterium deminutum sp. nov. (type strain KV-483(T)=NRRL B
      24453(T)=NBRC 101278(T)), Microbacterium pumilum sp. nov. (type strain KV
      488(T)=NRRL B-24452(T)=NBRC 101279(T)) and Microbacterium aoyamense sp. nov.
      (type strain KV-492(T)=NRRL B-24451(T)=NBRC 101280(T)).

PMID- 16957108
TI  - Rubritalea marina gen. nov., sp. nov., a marine representative of the phylum
      'Verrucomicrobia', isolated from a sponge (Porifera).
AB  - A marine bacterium, strain Pol012(T), was isolated from the Mediterranean sponge
      Axinella polypoides and subsequently characterized as belonging to subphylum 1 of
      the phylum 'Verrucomicrobia'. Strain Pol012(T) was non-motile, Gram-negative,
      coccoid or rod-shaped and red in colour. The menaquinones MK-8 and MK-9 were
      detected. The G+C content of the genomic DNA was 50.9 mol%. Growth was possible
      at temperatures between 8 and 30 degrees C and at pH values between 6.8 and 8.2.
      The closest cultured relative of strain Pol012(T) was Akkermansia muciniphila (83
      % sequence similarity), while the closest environmental 16S rRNA gene sequence
      was the marine clone Arctic96BD-2 (95 % sequence similarity). Strain Pol012(T) is
      the first marine pure-culture representative of 'Verrucomicrobia' subphylum 1 and
      represents a novel genus and species, for which the name Rubritalea marina gen.
      nov., sp. nov. is proposed. The type strain is Pol012(T) (=DSM 177716(T)=CIP
      108984(T)).

PMID- 16957109
TI  - Actinoplanes liguriensis sp. nov. and Actinoplanes teichomyceticus sp. nov.
AB  - The taxonomic status of 'Actinoplanes liguriae' A/6353 and 'Actinoplanes
      teichomyceticus' AB8327 was established by using a polyphasic approach. Strains
      A/6353 and AB8327 form distinct phylogenetic lineages in the 16S rRNA gene tree
      of members of the genus Actinoplanes and are related moderately and closely to
      Actinoplanes rectilineatus and Actinoplanes cyaneus, respectively. Morphological,
      cultural and physiological properties indicated that strains A/6353 and AB8327
      represent separate, novel species of the genus Actinoplanes, Actinoplanes
      liguriensis sp. nov. (type strain A/6353(T)=FH 2244(T)=DSM 43865(T)=ATCC
      31048(T)=BCRC 12121(T)=CBS 355.75(T)=IMSNU 22127(T)=JCM 3250(T)=KCTC 9536(T)=KCC
      A-0250(T)=NBRC 13997(T)=NCIMB 12636(T)=NRRL B-16723(T)=SANK 62178(T)) and
      Actinoplanes teichomyceticus sp. nov. (type strain AB8327(T)=FH 2149(T)=DSM
      43866(T)=ATCC 31121(T)=BCRC 12106(T)=FERM P-3462(T)=IMSNU 20043(T)=IMET
      9254(T)=JCM 3252(T)=KCC A-0252(T)=KCTC 9543(T)=NBRC 13999(T)=NCIMB 12640(T)=NRRL
      B-16726(T)=SANK 60479(T)).

PMID- 16957110
TI  - Paenibacillus gansuensis sp. nov., isolated from desert soil of Gansu Province in
      China.
AB  - A Gram-positive, endospore-forming, rod-shaped bacterium, designated strain
      B518(T), was isolated from a desert-soil sample from Gansu Province in China. The
      isolate was strictly aerobic and was motile by means of several flagella. The
      strain grew optimally at 35-40 degrees C and at pH 7.0-7.5. The predominant fatty
      acids of strain B518(T) were anteiso-C(15 : 0), C(16 : 0), anteiso-C(17 : 0), iso
      C(16 : 0) and iso-C(15 : 0). The G+C content of the genomic DNA was 50 mol% and
      the predominant quinone was MK-7. Comparative 16S rRNA gene sequence analyses
      showed that strain B518(T) formed a distinct phyletic line within the genus
      Paenibacillus and was most closely related to Paenibacillus chitinolyticus IFO
      15660(T), with a 16S rRNA gene sequence similarity of 95.8 %. The levels of 16S
      rRNA gene sequence similarity with respect to other type strains of Paenibacillus
      species were below 95.1 %. On the basis of the chemotaxonomic data and molecular
      properties, strain B518(T) represents a novel species within the genus
      Paenibacillus, for which the name Paenibacillus gansuensis sp. nov. is proposed.
      The type strain is B518(T) (=KCTC 3950(T)=DSM 16968(T)).

PMID- 16957111
TI  - Reclassification of Actinobacillus actinomycetemcomitans, Haemophilus
      aphrophilus, Haemophilus paraphrophilus and Haemophilus segnis as Aggregatibacter
      actinomycetemcomitans gen. nov., comb. nov., Aggregatibacter aphrophilus comb.
      nov. and Aggregatibacter segnis comb. nov., and emended description of
      Aggregatibacter aphrophilus to include V factor-dependent and V factor
      independent isolates.
AB  - The aim of this study was to reinvestigate the relationships and the generic
      affiliations of the species Actinobacillus actinomycetemcomitans, Haemophilus
      aphrophilus, Haemophilus paraphrophilus and Haemophilus segnis. The nicotinamide
      phosphoribosyltransferase gene (nadV) conferring V factor-independent growth was
      identified in Haemophilus aphrophilus. The gene encodes a polypeptide of 462
      amino acids that shows 74.5 % amino acid sequence identity to the corresponding
      enzyme from Actinobacillus actinomycetemcomitans. Ten isolates of Haemophilus
      paraphrophilus all carried a nadV pseudogene. DNA from Haemophilus aphrophilus
      was able to transform Haemophilus paraphrophilus into the NAD-independent
      phenotype. The transformants carried a full-length nadV inserted in the former
      locus of the pseudogene. The DNA-DNA relatedness between the type strains of
      Haemophilus aphrophilus and Haemophilus paraphrophilus was 77 %. We conclude that
      the division into two species Haemophilus aphrophilus and Haemophilus
      paraphrophilus is not justified and that Haemophilus paraphrophilus should be
      considered a later heterotypic synonym of Haemophilus aphrophilus. Forty strains
      of Actinobacillus actinomycetemcomitans, Haemophilus aphrophilus and Haemophilus
      segnis were investigated by multilocus sequence analysis. The 40 strains form a
      monophyletic group clearly separate from other evolutionary lineages of the
      family Pasteurellaceae. We propose the transfer of Actinobacillus
      actinomycetemcomitans, Haemophilus aphrophilus and Haemophilus segnis to a new
      genus Aggregatibacter gen. nov. as Aggregatibacter actinomycetemcomitans comb.
      nov. (the type species; type strain ATCC 33384(T)=CCUG 13227(T)=CIP 52.106(T)=DSM
      8324(T)=NCTC 9710(T)), Aggregatibacter aphrophilus comb. nov. (type strain ATCC
      33389(T)=CCUG 3715(T)=CIP 70.73(T)=NCTC 5906(T)) and Aggregatibacter segnis comb.
      nov. (type strain HK316(T)=ATCC 33393(T)=CCUG 10787(T)=CCUG 12838(T)=CIP
      103292(T)=NCTC 10977(T)). The species of the genus Aggregatibacter are
      independent of X factor and variably dependent on V factor for growth in vitro.

PMID- 16957112
TI  - Description of Sphingobium fuliginis sp. nov., a phenanthrene-degrading bacterium
      from a fly ash dumping site, and reclassification of Sphingomonas cloacae as
      Sphingobium cloacae comb. nov.
AB  - A phenanthrene-degrading bacterium, strain TKP(T), was isolated from a fly ash
      dumping site of the thermal power plant in Panki, Kanpur, India, by an enrichment
      culture method using phenanthrene as the sole source of carbon and energy.
      Phylogenetic analysis based on 16S rRNA gene sequences indicated that the strain
      belonged to the genus Sphingobium, as it showed highest sequence similarity to
      Sphingobium herbicidovorans DSM 11019(T) (97.3 %) and Sphingomonas cloacae JCM
      10874(T) (96.5 %), compared with only 91-93 % similarity to members of other
      genera such as Sphingomonas sensu stricto, Novosphingobium, Sphingopyxis and
      Sphingosinicella. In DNA-DNA hybridization experiments with strains that were
      closely related phylogenetically and in terms of 16S rRNA gene sequences, i.e.
      Sphingobium herbicidovorans DSM 11019(T) and Sphingomonas cloacae JCM 10874(T),
      strain TKP(T) showed less than 70 % relatedness. Strain TKP(T) contained
      sphingoglycolipids SGL-1 and SGL-2 and 18 : 1omega7c as the predominant fatty
      acid, with 16 : 0 as a minor component and 14 : 0 2-OH as the major 2-hydroxy
      fatty acid. Thus, phylogenetic analysis, DNA-DNA hybridization, fatty acid and
      polar lipid profiles and differences in physiological and morphological features
      from the most closely related members of the Sphingobium group showed that strain
      TKP(T) represents a distinct species of Sphingobium. The name Sphingobium
      fuliginis sp. nov. is proposed, with the type strain TKP(T) (=MTCC 7295(T)=CCM
      7327(T)). Sphingomonas cloacae JCM 10874(T) formed a coherent cluster with
      members of Sphingobium, did not reduce nitrate to nitrite and had a fatty acid
      profile similar to those of Sphingobium species; hence Sphingomonas cloacae
      should be transferred to the genus Sphingobium as Sphingobium cloacae comb. nov.,
      with the type strain JCM 10874(T) (=DSM 14926(T)).

PMID- 16957113
TI  - Pseudomonas pohangensis sp. nov., isolated from seashore sand in Korea.
AB  - A novel bacterium, designated strain H3-R18(T), was isolated from seashore sand
      collected from Homi cape, Pohang city, Korea. Cells were Gram-negative, aerobic,
      non-motile, cream-coloured, mesophilic and slightly halotolerant. 16S rRNA gene
      sequence analysis indicated that the organism was a member of the genus
      Pseudomonas, but the sequence showed < or =96.3 % sequence similarity to that of
      the type strains of all recognized Pseudomonas species. Highest sequence
      similarities were to Pseudomonas brenneri CFML 97-391(T) (96.3 %) and Pseudomonas
      migulae CIP 105470(T) (96.3 %). The major fatty acids were summed feature 3 and
      C(16 : 0), with lesser amounts of C(12 : 0), C(12 : 0) 3-OH, C(18 : 1)omega7c and
      C(14 : 0). The major isoprenoid quinone was Q-9. The DNA G+C content was 64.0
      mol%. The phylogenetic, phenotypic and genetic properties of strain H3-R18(T)
      suggest that it represents a novel species, for which the name Pseudomonas
      pohangensis sp. nov. is proposed. The type strain is H3-R18(T) (=KACC
      11517(T)=DSM 17875(T)).

PMID- 16957114
TI  - Rubrivivax benzoatilyticus sp. nov., an aromatic, hydrocarbon-degrading purple
      betaproteobacterium.
AB  - A brown-coloured bacterium was isolated from photoheterotrophic (benzoate)
      enrichments of flooded paddy soil from Andhra Pradesh, India. On the basis of 16S
      rRNA gene sequence analysis, strain JA2(T) was shown to belong to the class
      Betaproteobacteria, related to Rubrivivax gelatinosus (99 % sequence similarity).
      Cells of strain JA2(T) are Gram-negative, motile rods with monopolar single
      flagella. The strain contained bacteriochlorophyll a and most probably the
      carotenoids spirilloxanthin and sphaeroidene, but did not have internal membrane
      structures. Intact cells had absorption maxima at 378, 488, 520, 590, 802 and 884
      nm. No growth factors were required. Strain JA2(T) grew on benzoate, 2
      aminobenzoate (anthranilate), 4-aminobenzoate, 4-hydroxybenzoate, phthalate,
      phenylalanine, trans-cinnamate, benzamide, salicylate, cyclohexanone,
      cyclohexanol and cyclohexane-2-carboxylate as carbon sources and/or electron
      donors. The DNA G+C content was 74.9 mol%. Based on DNA-DNA hybridization
      studies, 16S rRNA gene sequence analysis and morphological and physiological
      characteristics, strain JA2(T) is different from representatives of other
      photosynthetic species of the Betaproteobacteria and was recognised as
      representing a novel species, for which the name Rubrivivax benzoatilyticus sp.
      nov. is proposed. The type strain is JA2(T) (=ATCC BAA-35(T)=JCM 13220(T)=MTCC
      7087(T)).

PMID- 16957115
TI  - Sphingomonas dokdonensis sp. nov., isolated from soil.
AB  - A Gram-negative, rod-shaped, Sphingomonas-like bacterial strain, DS-4(T), was
      isolated from soil of Dokdo, Korea, and its taxonomic position was investigated
      using a polyphasic approach. Strain DS-4(T) grew optimally on trypticase soy agar
      medium without NaCl at pH 6.0-6.5 and 25 degrees C. It contained Q-10 as the
      predominant ubiquinone and C(18 : 1)omega7c, C(16 : 0), C(14 : 0) 2-OH and C(16 :
      1)omega7c and/or iso-C(15 : 0) 2-OH as the major fatty acids. Sphingoglycolipid,
      phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol,
      phosphatidylethanolamine and unidentified phospholipid were the major polar
      lipids. The DNA G+C content was 66.9 mol%. Phylogenetic analysis based on 16S
      rRNA gene sequences showed that strain DS-4(T) fell within the evolutionary
      radiation comprising Sphingomonas species. Levels of 16S rRNA gene sequence
      similarity between strain DS-4(T) and the type strains of Sphingomonas species
      ranged from 93.0 to 97.6 %. DNA-DNA relatedness data and differential phenotypic
      properties, together with the phylogenetic distinctiveness, demonstrated that
      strain DS-4(T) differs from the recognized Sphingomonas species. On the basis of
      phenotypic, phylogenetic and genetic data, this strain represents a novel species
      of the genus Sphingomonas, for which the name Sphingomonas dokdonensis sp. nov.
      is proposed, with DS-4(T) (=KCTC 12541(T)=CIP 108841(T)) as the type strain.

PMID- 16957116
TI  - Burkholderia oklahomensis sp. nov., a Burkholderia pseudomallei-like species
      formerly known as the Oklahoma strain of Pseudomonas pseudomallei.
AB  - C6786, the clinical isolate of the 'Oklahoma' strain of Pseudomonas (now
      Burkholderia) pseudomallei, was originally isolated in 1973 from a wound
      infection resulting from a farming accident in Oklahoma, USA. Environmental
      isolates C7532 and C7533 from the Oklahoma accident site were found to match
      C6786. These three isolates and a clinical isolate originally identified as B.
      pseudomallei that was recovered from a person in Georgia, USA, involved in an
      automobile accident were characterized by biochemical, 16S rRNA gene sequencing,
      multilocus sequence typing and DNA-DNA hybridization analyses. Results indicated
      that these strains comprise a novel species. The name Burkholderia oklahomensis
      sp. nov. is proposed, with strain C6786(T) (=LMG 23618(T)=NCTC 13387(T)=CCUG
      51349(T)) as the type strain.

PMID- 16957117
TI  - Rheinheimera perlucida sp. nov., a marine bacterium of the Gammaproteobacteria
      isolated from surface water of the central Baltic Sea.
AB  - A bacterial isolate from the Baltic Sea, BA131(T), was characterized for its
      physiological and biochemical features, fatty acid profile, G+C content and
      phylogenetic position based on comparative 16S rRNA gene sequence analysis. The
      strain was isolated from surface water of the central Baltic Sea during the decay
      of a plankton bloom. Phylogenetic analyses of the 16S rRNA gene sequence revealed
      a clear affiliation with the Gammaproteobacteria, and showed closest phylogenetic
      relationships with the genera Alishewanella and Rheinheimera. The G+C content of
      the DNA of strain BA131(T) was 48.9 mol%. Cells were non-pigmented, Gram
      negative, rod-shaped, motile by means of a single polar flagellum and catalase-
      and oxidase-positive. Growth was observed at salinities from 0 to 8 %, with an
      optimum at 1-3 %. Temperature for growth ranged from 4 to 37 degrees C, with an
      optimum around 25 degrees C. The fatty acids were dominated by 16 : 0 (17-18 %)
      and by unsaturated compounds (>61 % of the total): 16 : 1omega7c (24-33 %), 17 :
      1omega8c (14-18 %) and 18 : 1omega7c (9-12 %). Based on the data presented,
      BA131(T) is proposed as the type strain of a novel species of the genus
      Rheinheimera, Rheinheimera perlucida sp. nov. The type strain is BA131(T) (=LMG
      23581(T)=CIP 109200(T)).

PMID- 16957118
TI  - Glaciecola nitratireducens sp. nov., isolated from seawater.
AB  - A marine bacterial strain, FR1064(T), was isolated from a surface seawater sample
      collected off Jeju Island, South Korea. Phylogenetic analysis based on 16S rRNA
      gene sequences indicated that the isolate belonged to the Gammaproteobacteria and
      was related to the genus Glaciecola with 97.6 % sequence similarity to Glaciecola
      pallidula, its nearest phylogenetic neighbour. DNA-DNA relatedness between strain
      FR1064(T) and G. pallidula ACAM 615(T) was 55 %. Cells of the novel isolate were
      Gram-negative, aerobic, rod-shaped, motile and halophilic, with an optimum sea
      salts concentration of 4-7 %. The major fatty acids were straight-chain saturated
      (C(16 : 0)), summed feature 3 and monounsaturated fatty acid C(18 : 1). The DNA
      G+C content was 44 mol%. Several phenotypic characteristics differentiated the
      novel isolate from all previously described members of the genus Glaciecola. The
      polyphasic data obtained in this study clearly demonstrate that strain FR1064(T)
      represents a novel species of the genus Glaciecola. The name Glaciecola
      nitratireducens sp. nov. is therefore proposed, with strain FR1064(T) (=KCTC
      12276(T)=JCM 12485(T)) as the type strain.

PMID- 16957119
TI  - Hymenobacter rigui sp. nov., isolated from wetland freshwater.
AB  - A non-motile, rod-shaped and pinkish-red-pigmented bacterium, designated strain
      WPCB131(T), was isolated from freshwater of Woopo wetland, Republic of Korea.
      Phylogenetic analysis based on 16S rRNA gene sequencing indicated that this
      isolate represents a novel member of the genus Hymenobacter with sequence
      similarities of 93.2-95.5 % to known Hymenobacter species. No other taxa in the
      phylum Bacteroidetes showed more than 90 % sequence similarity to the isolate.
      Cells were Gram-negative, oxidase-negative and catalase-positive. Optimum growth
      was observed at pH 6 and 30 degrees C. The major fatty acids were iso-C(15 : 0)
      (34.8 %), C(16 : 1)omega5c (15.0 %), anteiso-C(17 : 1) B/iso-C(17 : 1) I (14.4 %)
      and C(16 : 1)omega7c/iso-C(15 : 0) 2-OH (13.8 %). The DNA G+C content of strain
      WPCB131(T) was 65 mol%. The isolate could be readily distinguished from other
      Hymenobacter species using a combination of phenotypic characters. On the basis
      of the polyphasic evidence presented in this study, it is proposed that strain
      WPCB131(T) (=IMSNU 14116(T)=KCTC 12533(T)=NBRC 101118(T)) represents a novel
      species, Hymenobacter rigui sp. nov.

PMID- 16957120
TI  - Pseudonocardia oroxyli sp. nov., a novel actinomycete isolated from surface
      sterilized Oroxylum indicum root.
AB  - A high-G+C-content, Gram-positive bacterium, strain D10(T), was isolated from the
      root of Oroxylum indicum, a Chinese medicinal plant. Based on 16S rRNA gene
      sequence analysis, strain D10(T) was a member of the genus Pseudonocardia and was
      most closely related, albeit loosely, to Pseudonocardia halophobica.
      Morphological and chemotaxonomic characteristics support the affiliation of
      strain D10(T) to the genus Pseudonocardia. Results of DNA-DNA hybridization and
      physiological and biochemical tests allowed genotypic and phenotypic
      differentiation of strain D10(T) from related Pseudonocardia species. Strain
      D10(T) (=CGMCC 4.3143(T)=DSM 44984(T)) therefore represents a novel species, for
      which the name Pseudonocardia oroxyli sp. nov. is proposed.

PMID- 16957121
TI  - Loktanella koreensis sp. nov., isolated from sea sand in Korea.
AB  - A bacterial strain, GA2-M3(T), isolated from a sea-sand sample in Korea, was
      subjected to polyphasic taxonomic characterization. Cells of strain GA2-M3(T)
      were Gram-negative, non-motile, non-spore-forming and short rod- to ovoid-shaped.
      Comparative 16S rRNA gene sequencing studies confirmed that the bacterium fell
      within the radiation of the genus Loktanella. Similarity levels between the 16S
      rRNA gene sequence of strain GA2-M3(T) and those of type strains of Loktanella
      species with validly published names were 93.5-96.1 %; highest sequence
      similarity was with Loktanella rosea. The G+C content of the genomic DNA of
      strain GA2-M3(T) was 60.0 mol% and the predominant ubiquinone was Q-10. Major
      fatty acids were 18 : 1omega7c, 18 : 0 and 18 : 1omega7c 11-methyl. On the basis
      of the evidence presented, it is proposed that strain GA2-M3(T) represents a
      novel species, for which the name Loktanella koreensis sp. nov. is proposed. The
      type strain is GA2-M3(T) (=KACC 11519(T)=DSM 17925(T)).

PMID- 16957122
TI  - Nocardia harenae sp. nov., an actinomycete isolated from beach sand.
AB  - A novel actinomycete, strain WS-26(T), was isolated from beach sand on the coast
      of Jeju Island, Republic of Korea, and subjected to a polyphasic taxonomic
      characterization. The organism produced reddish orange-coloured substrate
      mycelium and white aerial mycelium, both of which fragmented into rod-shaped
      elements. A neighbour-joining tree, based on 16S rRNA gene sequence studies,
      revealed that the isolate formed a distinct branch at the base of a cluster that
      included Nocardia carnea, N. flavorosea, N. pigrifrangens, N. sienata and N.
      testacea. This branching pattern was also found in a tree constructed using the
      maximum-likelihood method, but was not supported by the maximum-parsimony method.
      Levels of 16S rRNA gene sequence similarity between the isolate and its
      phylogenetic neighbours ranged from 96.5 to 97.8 %. Chemotaxonomic properties,
      such as the principal amino acid of peptidoglycan, predominant menaquinone and
      polar lipids, supported its assignment to the genus Nocardia. On the basis of
      phenotypic and phylogenetic data, the organism was different from Nocardia
      species with validly published names. The name Nocardia harenae sp. nov. is
      proposed, with WS-26(T) (=KCCM 42317(T)=NRRL B-24459(T)) as the type strain.

PMID- 16957123
TI  - Lactobacillus siliginis sp. nov., isolated from wheat sourdough in South Korea.
AB  - The taxonomic position of two lactic-acid-producing bacterial strains, isolated
      from wheat sourdough in South Korea, was studied using a polyphasic approach.
      Phylogenetic analysis on the basis of 16S rRNA gene sequences and biochemical and
      physiological characteristics indicated these two strains to be members of the
      genus Lactobacillus. They had high 16S rRNA gene sequence similarity (98.5 %)
      with Lactobacillus rossiae DSM 15814(T) and very low (<94.0 %) similarity with
      any other recognized species of the genus Lactobacillus. These two strains
      (designated M1-212(T) and M2-236) were heterofermentative, facultatively
      anaerobic, Gram-positive, non-spore-forming, non-motile, short rod-shaped
      bacteria. The optimum growth temperature for these strains was 30 degrees C (no
      growth at 15 or 45 degrees C) and they were able to tolerate 5 % (w/v) NaCl. The
      G+C content of the genomic DNA of the two strains was 45.5 mol%, within the range
      of values reported for the genus Lactobacillus (32-53 mol%). The peptidoglycan
      was of the A3alpha (l-lys-d-glu-l-Ala) type. Physiological, biochemical and
      genotypic data, as well as results of DNA-DNA hybridization of the genomic DNA
      with one of the closest phylogenetic relatives, L. rossiae DSM 15814(T),
      indicated that the strains represent a novel species of the genus Lactobacillus,
      for which the name Lactobacillus siliginis sp. nov. is proposed. The type strain
      is M1-212(T) (=KCTC 3985(T)=NBRC 101315(T)).

PMID- 16957124
TI  - Xylanibacter oryzae gen. nov., sp. nov., a novel strictly anaerobic, Gram
      negative, xylanolytic bacterium isolated from rice-plant residue in flooded rice
      field soil in Japan.
AB  - A strictly anaerobic, xylanolytic bacterium, strain KB3(T), isolated from rice
      plant residue in flooded anoxic rice-field soil in Japan, was characterized
      phenotypically and phylogenetically. Cells were Gram-negative, non-motile, non
      spore-forming, short to filamentous rods. Growth of the strain was remarkably
      stimulated by the addition of haemin to the medium. The novel strain utilized
      various sugars including xylan, xylose, pectin and carboxymethylcellulose and
      produced acetate, propionate and succinate with a small amount of malate.
      Propionate production was stimulated by the addition of a B-vitamin mixture or
      cobalamin to the medium. The novel strain was slightly acidophilic with an
      optimum pH 5.7-6.2 and the optimum growth temperature was 30 degrees C. Oxidase,
      catalase and nitrate-reducing activities were negative. Aesculin was hydrolysed.
      The major cellular fatty acids were anteiso-C(15 : 0) and iso-3-OH C(17 : 0). The
      major respiratory quinones were menaquinones MK-12(H(2)) and MK-13(H(2)). The
      genomic DNA G+C content was 43.6 mol%. Phylogenetic analysis based on 16S rRNA
      gene sequence placed the strain in the phylum Bacteroidetes. The closest related
      species was Prevotella bivia with a 16S rRNA gene sequence similarity of 89.5 %.
      Prevotella albensis and Prevotella oulorum were the next closest recognized
      species with sequence similarities of 89.1 %. Based on a comprehensive
      examination of the differences in phylogenetic, ecological, physiological and
      chemotaxonomic characteristics of strain KB3(T) and those of related species, a
      novel genus and species, Xylanibacter oryzae gen. nov., sp. nov., is proposed to
      accommodate strain KB3(T). The type strain of the novel species is KB3(T) (=JCM
      13648(T)=DSM 17970(T)).

PMID- 16957125
TI  - Transfer of [Flexibacter] sancti, [Flexibacter] filiformis, [Flexibacter]
      japonensis and [Cytophaga] arvensicola to the genus Chitinophaga and description
      of Chitinophaga skermanii sp. nov.
AB  - Analysis of the 16S rRNA gene sequences of species currently assigned to the
      genus Flexibacter has shown extensive intrageneric phylogenetic heterogeneity. It
      has been shown in previous studies that the species [Flexibacter] sancti,
      [Flexibacter] filiformis and [Flexibacter] japonensis were most closely related
      to Chitinophaga pinensis. In addition, [Cytophaga] arvensicola and species of the
      genus Terrimonas also clustered into this phylogenetic group. Although the
      similarities of 16S rRNA gene sequences were low (88.5-96.4 %), there is no
      evidence for clear phenotypic differences between these organisms that justify
      assignment to different genera. A proposal is made to transfer these species to
      the genus Chitinophaga as Chitinophaga sancti comb. nov., Chitinophaga filiformis
      comb. nov., Chitinophaga japonenis comb. nov. and Chitinophaga arvensicola comb.
      nov. on the basis of phylogenetic and phenotypic data. Furthermore, a novel
      species is described within this genus, Chitinophaga skermanii sp. nov., with
      strain CC-SG1B(T) (=CCUG 52510(T)=CIP 109140(T)) as the type strain.

PMID- 16957126
TI  - Idiomarina homiensis sp. nov., isolated from seashore sand in Korea.
AB  - A halophilic, aerobic bacterium, designated PO-M2(T), was isolated from seashore
      sand, from Pohang, Korea and characterized on the basis of physiological and
      biochemical features. Phylogenetic analysis of 16S rRNA gene sequences revealed a
      clear affiliation of the novel strain with members of the genus Idiomarina.
      Sequence similarities between strain PO-M2(T) and the type strains of species
      belonging to the genus Idiomarina ranged from 94.3 to 95.5 %. Cells of strain PO
      M2(T) were straight or slightly curved rods and formed light-yellow colonies on
      marine agar medium. The major isoprenoid quinone was ubiquinone (Q-8) and the
      predominant cellular fatty acids were C(15 : 0) iso (19.3 %), C(17 : 1)omega9c
      iso (11.9 %), C(17 : 0) iso (10.9 %), C(18 : 1)omega7c (10.4 %), C(16 : 0) (9.0
      %) and C(16 : 1)omega7c and/or C(15 : 0) iso 2-OH (7.2 %). The G+C content of the
      DNA was 45.1 mol%. Based on physiological, biochemical and chemotaxonomic traits
      and comparative 16S rRNA gene sequence analysis, it is demonstrated that the
      isolate represents a novel species of the genus Idiomarina, for which the name
      Idiomarina homiensis sp. nov. is proposed. The type strain is PO-M2(T) (=KACC
      11514(T)=DSM 17923(T)).

PMID- 16957127
TI  - New insights into the phylogeny of Entamoeba species provided by analysis of four
      new small-subunit rRNA genes.
AB  - Sequences of small-subunit rRNA genes have been obtained for four new isolates of
      Entamoeba. Phylogenetic analyses give new insights into the evolution of these
      organisms. A novel Entamoeba from pigs in Vietnam that produces uninucleate cysts
      proved to be unrelated to other uninucleated cyst-producing species. Revival of
      the name Entamoeba suis for this organism is proposed. Instead of being related
      to Entamoeba polecki, it shares a recent common ancestor with the non-encysting
      Entamoeba gingivalis in a lineage that is basal to the tetranucleate cyst
      producing clade. This suggests that species producing cysts with four nuclei are
      descended from an ancestor that produced cysts with a single nucleus. An
      Entamoeba from a horse was isolated in culture. No cysts were observed in the
      original stool sample but the sequence is placed unequivocally within the clade
      of tetranucleate cyst-producing species with no other sequences being
      specifically related. Revival of the name Entamoeba equi for this organism is
      proposed. The Entamoeba ecuadoriensis sequence was found to be the most closely
      related to Entamoeba histolytica and Entamoeba dispar, as predicted, despite the
      organism having been an environmental isolate originally assigned to Entamoeba
      moshkovskii. Finally, a partial E. polecki gene sequence from a pig proved to be
      virtually identical to that of Entamoeba struthionis from an ostrich, suggesting
      that the latter name is a synonym.

PMID- 16957128
TI  - Cryptococcus mujuensis sp. nov. and Cryptococcus cuniculi sp. nov.,
      basidiomycetous yeasts isolated from wild rabbit faeces.
AB  - Two previously undescribed anamorphic yeasts, strains T-11(T) and T-26(T),
      recovered from wild rabbit faecal pellets collected in Muju, Korea, were
      identified using phenotypic and molecular taxonomic methods. The isolates were
      characterized by the proliferation of budding cells, positive diazonium blue B
      and urease reactions, the presence of Q-10 as the major ubiquinone, the presence
      of xylose in whole-cell hydrolysates and the inability to ferment sugars.
      Phylogenetic analyses based on 26S rRNA gene partial sequences revealed that
      strain T-11(T) was located in the Bulleromyces clade and was related to
      Sirobasidium intermedium, Tremella exigua, Cryptococcus cellulolyticus and
      Bullera pseudoalba. Strain T-26(T) was located in the Mesenterica clade and was
      closely related to Cryptococcus sp. F6 and Cryptococcus heveanensis CBS 8976.
      Sequence divergence values of more than 4 % from other described Cryptococcus
      species, together with the phenotypic differences, showed that the isolated
      yeasts represent previously unrecognized members of this genus. Therefore, two
      novel yeast species are proposed: Cryptococcus mujuensis sp. nov., with strain T
      11(T) (=KCTC 17231(T)=CBS 10308(T)) as the type strain, and Cryptococcus cuniculi
      sp. nov., with strain T-26(T) (=KCTC 17232(T)=CBS 10309(T)) as the type strain.

PMID- 16957129
TI  - Metschnikowia sinensis sp. nov., Metschnikowia zizyphicola sp. nov. and
      Metschnikowia shanxiensis sp. nov., novel yeast species from jujube fruit.
AB  - Eight yeast strains were isolated from jujube fruit surfaces collected in Shanxi
      and Shandong Provinces, China. All eight strains produced needle-shaped
      ascospores under suitable conditions. Three separate groups, representing three
      novel species in the genus Metschnikowia, were recognized by sequence comparisons
      of the 26S rDNA D1/D2 domain and internal transcribed spacer (ITS) region. The
      names Metschnikowia sinensis sp. nov. (type strain XY103(T)=AS 2.3110(T)=CBS
      10357(T)), Metschnikowia zizyphicola sp. nov. (type strain XY201(T)=AS
      2.3111(T)=CBS 10358(T)) and Metschnikowia shanxiensis sp. nov. (type strain
      XY801(T)=AS 2.3112(T)=CBS 10359(T)) are proposed for the three novel species.
      Phylogenetic analysis of the 26S rDNA D1/D2 domain sequence showed that these
      three novel species are clustered in a clade together with the previously
      described species Metschnikowia fructicola, Metschnikowia andauensis,
      Metschnikowia pulcherrima and Metschnikowia chrysoperlae.

PMID- 16957130
TI  - Prevalence of repetitive and reward-seeking behaviors in Parkinson disease.
AB  - We surveyed 297 patients with Parkinson disease (PD) with systematic screens and
      rigorous definitional criteria. Pathologic hypersexuality lifetime prevalence was
      2.4%. Compulsive shopping was 0.7%. Combined with our pathologic gambling data,
      the lifetime prevalence of these behaviors was 6.1% and increases to 13.7% in
      patients on dopamine agonists.

PMID- 16957131
TI  - Marty Gibbs's 30 years at the helm of Plant Physiology.

PMID- 16957132
TI  - RT-Plant Physiology: Full Open Access Publishing at No Charge to ASPB Members.

PMID- 16957133
TI  - Natural experiments indicate that geomagnetic variations cause spatial and
      temporal variations in coconut palm asymmetry.

PMID- 16957134
TI  - The-more-the-better and the-less-the-better.

PMID- 16957135
TI  - Ejaculate volume is seriously underestimated when semen is pipetted or decanted
      into cylinders from the collection vessel.

PMID- 16957136
TI  - Effect of testosterone on intracavernous pressure elicited with electrical
      stimulation of the medial preoptic area and cavernous nerve in male rats.
AB  - We studied the effects of castration and testosterone (T) replacement on
      intracavernous pressure (ICP) elicited with electrical stimulation of the medial
      preoptic area (MPOA) and cavernous nerve (CN) in male rats. We measured the ICP
      during electrical stimulation of the MPOA and CN in castrated male rats with and
      without testosterone replacement. The experimental group consisted of 20-week-old
      male rats at 2 weeks (n=8), 4 weeks (n=8) and 8 weeks (n=8) after castration, and
      at 8 weeks after castration with T replacement (n=4). Intact 20-week-old rats
      (n=8) served as controls. The erectile response was expressed as the ICP/blood
      pressure (BP) ratio. The ICP/BP ratios during CN stimulation of the animals at 2,
      4, and 8 weeks after castration were significantly lower than those of the intact
      animals. However, the erectile responses were not eliminated. In contrast to
      these peripherally evoked responses, erectile responses elicited by electrical
      stimulation of the MPOA were eliminated following castration. After testosterone
      replacement, both erectile responses were restored. Testosterone plays important
      roles in both the central and peripheral neural pathways for the maintenance and
      restoration of erectile capacity. The central control of erection shows more
      extensive changes following testosterone replacement than the peripheral control.

PMID- 16957137
TI  - Effect of posture and clothing on scrotal temperature in fertile men.
AB  - Investigation of the effects of body position and clothing on the temperature of
      the scrotum has given discordant results. The aim of the present study was to
      evaluate these effects in 13 fertile male volunteers in successive positions each
      held for 15 minutes, either Supine, Standing, Seated with legs apart, and Seated
      with legs crossed (n = 8) or Standing, Seated with legs crossed, and Standing (n
      = 5), at first naked and then clothed. The Standing naked position was that in
      which scrotal temperature reached the lowest point. Clothing increased the
      scrotal temperature compared with the naked state, whatever the position. The
      Seated with legs crossed position had specific characteristics: in the naked
      state, it was thermogenic and increased scrotal temperature as much as clothing
      in the Supine or Standing positions; in the clothed state, the increase in
      temperature was less than expected, which could indicate that local mechanisms
      are involved. Moreover, the Seated with legs crossed position had a persisting
      effect on scrotal temperature in the next position. These results have both
      pathophysiological and epidemiological implications.

PMID- 16957138
TI  - Association of long polyglycine tracts (GGN repeats) in exon 1 of the androgen
      receptor gene with cryptorchidism and penile hypospadias in Iranian patients.
AB  - Hypospadias (a urethral orifice located along the ventral side of the penis) and
      cryptorchidism (failure of the testes to descend into the scrotal sacs) are the 2
      most common congenital malformations in males, affecting 0.3%-0.7% and 2%-4%,
      respectively, at birth. To study the association of CAG/GGN trinucleotide repeats
      in the androgen receptor gene with cryptorchidism and hypospadias in an Iranian
      population, we performed a case-control study of 76 cryptorchid and 92
      hypospadiac (divided into subgroups of glanular, penile, and penoscrotal
      hypospadias) Iranian males. The length of the CAG/GGN repeat segment was
      evaluated by using polymerase chain reaction (PCR) sequencing in exon 1 and PCR
      single-strand conformation polymorphism (PCR-SSCP) in exons 2-8. There were no
      significant differences in CAG lengths between the cases and controls, but GGN
      numbers were found to be significantly higher (median, 24 vs 22) among both
      subjects with penile hypospadias (P = .018) and those with a history of
      cryptorchidism (P = .001) compared with controls. In addition, the GGN numbers
      among subjects with penile hypospadias were significantly different compared with
      the 2 other subgroups of hypospadias (P = .001). We were able to identify 12
      different CAG alleles and 8 different GGN alleles in the cryptorchid group.
      Although further studies are needed to elucidate the possible role of specific
      CAG/GGC combinations as a susceptible factor, our data suggested the possible
      association between polyglycin tract polymorphism in androgen receptor gene and
      cryptorchidism.

PMID- 16957139
TI  - Apoptosis and molecular pathways in the seminiferous epithelium of aged and
      photoinhibited Syrian hamsters (Mesocricetus auratus).
AB  - Aging and short photoperiod exposure induce germ cell apoptosis in the Syrian
      hamster; however, the specific germ cells affected and the molecular pathways
      triggered have not been elucidated. We analyzed germ cell apoptosis and the
      expression of the Fas/Fas-L system, Bcl-2 family, and p53 in aged and
      photoinhibited hamsters and compared with those young maintained in natural
      photoperiod. Aging increased apoptosis in spermatogonia and spermatocytes, but in
      photoinhibited hamster testes only an increase in apoptotic spermatocytes was
      observed. Apoptosis was higher in aged hamsters in stages I-IV, V-VI and VII
      VIII. Aging increased apoptosis of spermatogonia in stages I-IV and V-VI.
      Apoptotic pachytene spermatocytes were significantly higher in stages I-IV, V-VI,
      and VII-VIII in aging. Apoptotic preleptotene and pachytene spermatocytes were
      higher in aging, but no differences were observed in leptotene-zygotene. Fas-L
      was expressed by Sertoli cells, of young, aged, and photoinhibited hamsters. Bcl
      x(L) was strongly expressed in germ cells on young hamsters and slightly in aging
      and after short photoperiod exposure. Spermatocytes of photoinhibited hamsters
      were intensively stained with Fas, Bax, Bcl-xs/L, and p53. In conclusion, aging
      increases apoptosis in spermatogonia and spermatocytes, depending on the stage of
      the seminiferous epithelium cycle, whereas after a short photoperiod exposure
      only an increase in apoptotic spermatocytes is observed. The results suggest that
      Fas, Bcl-x(L), Bax, and p53 participate in germ cell apoptosis induction after
      short photoperiod exposure, whereas only Bcl-x(L) is involved in aging.

PMID- 16957140
TI  - Correlation between semen parameters and the Hamster Egg Penetration Test (HEPT)
      among fertile and subfertile men in Singapore.
AB  - The objective of this retrospective study was to distinguish between fertile and
      subfertile men based on their semen parameters and hamster egg penetration test
      (HEPT) outcome. This study involved 110 subfertile men recruited from an
      infertility clinic and 48 fertile men attending an antenatal clinic in Singapore.
      The men were required to donate a semen specimen for semen analysis and HEPT
      assay. The results indicated that the subfertile group had significantly lower
      normal sperm morphology according to the Tygerberg strict criteria, and lower
      progressive motility (P < .05). Semen volume, density, HEPT decondensation rate,
      and sperm penetration index were not significantly different between the 2
      groups. Receiver operating characteristic curve analysis indicated that sperm
      morphology had the highest predictive power of 65.7% with a threshold value of
      7%, and progressive motility had a predictive power of 61.8% with a threshold
      value of 50%. Using the tenth percentile of the fertile population as the cutoff,
      lower adjusted thresholds of 3% for sperm morphology and 28% for progressive
      motility were obtained, giving higher positive predictive values of 81.8% and
      84.4%, respectively. This study shows that these new cutoff values can be used to
      screen the general population to identify subfertile men. In contrast, the HEPT
      proved to be an insensitive and unreliable assay in identifying subfertile males.
      To our knowledge the comparison of HEPT and semen parameters between subfertile
      and fertile men has not been previously reported in an Asian population.

PMID- 16957141
TI  - Urinary prostate-specific antigen is a noninvasive indicator of sexual
      development in male children.
AB  - Testicular androgen induces the synthesis of prostate specific antigen (PSA) in
      acinar epithelial cells of the prostate. We examined PSA activity in urine from
      136 male children from birth up to 17 years of age. We detected PSA at various
      intervals in early infant urine over a period of 1-4 months. During this period,
      urinary secretion of testosterone (T) gradually declined, accompanied by 1 or
      more surges of T prior to a transient increase in PSA in urine from full- and
      preterm infants (67%, n = 6). Although mean urinary T concentrations during
      elevations of PSA in preterm infants were 3.1 and 5.6 times greater than in full
      term infants and adults, the overall mean urinary PSA concentration of full and
      preterm infants was just 45% and 18% that of adults, respectively. PSA was not
      detected in children aged 0.3 to 9 years, after which a gradual increase in
      urinary PSA activity was observed after 10 years of age. Urinary PSA activity was
      markedly persistent after Tanner stage III pubertal development. To our
      knowledge, this is the first study to demonstrate an induction of PSA during
      early infancy by bioactive T in normally developing human males. We conclude that
      urinary PSA is a non-invasive, useful indicator for developmental studies from
      neonatal and adolescent males, which can be measured with a confirmatory
      semiquantitative PSA assay.

PMID- 16957142
TI  - Images in clinical medicine. Catamenial pneumothorax.

PMID- 16957143
TI  - Going beyond disease to address disability.

PMID- 16957144
TI  - The script.

PMID- 16957145
TI  - DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant
      chemotherapy.
AB  - BACKGROUND: Adjuvant cisplatin-based chemotherapy improves survival among
      patients with completely resected non-small-cell lung cancer, but there is no
      validated clinical or biologic predictor of the benefit of chemotherapy. METHODS:
      We used immunohistochemical analysis to determine the expression of the excision
      repair cross-complementation group 1 (ERCC1) protein in operative specimens of
      non-small-cell lung cancer. The patients had been enrolled in the International
      Adjuvant Lung Cancer Trial, thereby allowing a comparison of the effect of
      adjuvant cisplatin-based chemotherapy on survival, according to ERCC1 expression.
      Overall survival was analyzed with a Cox model adjusted for clinical and
      pathological factors. RESULTS: Among 761 tumors, ERCC1 expression was positive in
      335 (44%) and negative in 426 (56%). A benefit from cisplatin-based adjuvant
      chemotherapy was associated with the absence of ERCC1 (test for interaction,
      P=0.009). Adjuvant chemotherapy, as compared with observation, significantly
      prolonged survival among patients with ERCC1-negative tumors (adjusted hazard
      ratio for death, 0.65; 95% confidence interval [CI], 0.50 to 0.86; P=0.002) but
      not among patients with ERCC1-positive tumors (adjusted hazard ratio for death,
      1.14; 95% CI, 0.84 to 1.55; P=0.40). Among patients who did not receive adjuvant
      chemotherapy, those with ERCC1-positive tumors survived longer than those with
      ERCC1-negative tumors (adjusted hazard ratio for death, 0.66; 95% CI, 0.49 to
      0.90; P=0.009). CONCLUSIONS: Patients with completely resected non-small-cell
      lung cancer and ERCC1-negative tumors appear to benefit from adjuvant cisplatin
      based chemotherapy, whereas patients with ERCC1-positive tumors do not.

PMID- 16957146
TI  - Soluble endoglin and other circulating antiangiogenic factors in preeclampsia.
AB  - BACKGROUND: Alterations in circulating soluble fms-like tyrosine kinase 1
      (sFlt1), an antiangiogenic protein, and placental growth factor (PlGF), a
      proangiogenic protein, appear to be involved in the pathogenesis of preeclampsia.
      Since soluble endoglin, another antiangiogenic protein, acts together with sFlt1
      to induce a severe preeclampsia-like syndrome in pregnant rats, we examined
      whether it is associated with preeclampsia in women. METHODS: We performed a
      nested case-control study of healthy nulliparous women within the Calcium for
      Preeclampsia Prevention trial. The study included all 72 women who had preterm
      preeclampsia (<37 weeks), as well as 480 randomly selected women--120 women with
      preeclampsia at term (at > or =37 weeks), 120 women with gestational
      hypertension, 120 normotensive women who delivered infants who were small for
      gestational age, and 120 normotensive controls who delivered infants who were not
      small for gestational age. RESULTS: Circulating soluble endoglin levels increased
      markedly beginning 2 to 3 months before the onset of preeclampsia. After the
      onset of clinical disease, the mean serum level in women with preterm
      preeclampsia was 46.4 ng per milliliter, as compared with 9.8 ng per milliliter
      in controls (P<0.001). The mean serum level in women with preeclampsia at term
      was 31.0 ng per milliliter, as compared with 13.3 ng per milliliter in controls
      (P<0.001). Beginning at 17 weeks through 20 weeks of gestation, soluble endoglin
      levels were significantly higher in women in whom preterm preeclampsia later
      developed than in controls (10.2 ng per milliliter vs. 5.8 ng per milliliter,
      P<0.001), and at 25 through 28 weeks of gestation, the levels were significantly
      higher in women in whom term preeclampsia developed than in controls (8.5 ng per
      milliliter vs. 5.9 ng per milliliter, P<0.001). An increased level of soluble
      endoglin was usually accompanied by an increased ratio of sFlt1:PlGF. The risk of
      preeclampsia was greatest among women in the highest quartile of the control
      distributions for both biomarkers but not for either biomarker alone.
      CONCLUSIONS: Rising circulating levels of soluble endoglin and ratios of
      sFlt1:PlGF herald the onset of preeclampsia.

PMID- 16957148
TI  - Clinical practice. Social anxiety disorder.

PMID- 16957147
TI  - Enoxaparin versus unfractionated heparin in elective percutaneous coronary
      intervention.
AB  - BACKGROUND: Despite its limitations, unfractionated heparin has been the standard
      anticoagulant used during percutaneous coronary intervention (PCI). Several small
      studies have suggested that intravenous enoxaparin may be a safe and effective
      alternative. Our primary aim was to assess the safety of enoxaparin as compared
      with that of unfractionated heparin in elective PCI. METHODS: In this
      prospective, open-label, multicenter, randomized trial, we randomly assigned 3528
      patients with PCI to receive enoxaparin (0.5 or 0.75 mg per kilogram of body
      weight) or unfractionated heparin adjusted for activated clotting time,
      stratified according to the use or nonuse of glycoprotein IIb/IIIa inhibitors.
      The primary end point was the incidence of major or minor bleeding that was not
      related to coronary-artery bypass grafting. The main secondary end point was the
      percentage of patients in whom the target anticoagulation levels were reached.
      RESULTS: Enoxaparin at a dose of 0.5 mg per kilogram was associated with a
      significant reduction in the rate of non-CABG-related bleeding in the first 48
      hours, as compared with unfractionated heparin (5.9% vs. 8.5%; absolute
      difference, -2.6; 95% confidence interval [CI], -4.7 to -0.6; P=0.01), but the
      higher enoxaparin dose was not (6.5% vs. 8.5%; absolute difference, -2.0; 95% CI,
      -4.0 to 0.0; P=0.051). The incidence of major bleeding was significantly reduced
      in both enoxaparin groups, as compared with the unfractionated heparin group.
      Target anticoagulation levels were reached in significantly more patients who
      received enoxaparin (0.5-mg-per-kilogram dose, 79%; 0.75-mg-per-kilogram dose,
      92%) than who received unfractionated heparin (20%, P<0.001). CONCLUSIONS: In
      elective PCI, a single intravenous bolus of 0.5 mg of enoxaparin per kilogram is
      associated with reduced rates of bleeding, and a dose of 0.75 mg per kilogram
      yields rates similar to those for unfractionated heparin, with more predictable
      anticoagulation levels. The trial was not large enough to provide a definitive
      comparison of efficacy in the prevention of ischemic events. (ClinicalTrials.gov
      number, NCT00077844 [ClinicalTrials.gov].).

PMID- 16957149
TI  - Oncogene-induced cell senescence--halting on the road to cancer.

PMID- 16957150
TI  - Images in clinical medicine. Congenital erythropoietic porphyria.

PMID- 16957151
TI  - Clinical problem-solving. More than meets the eye.

PMID- 16957152
TI  - ERCC1 measurements in clinical oncology.

PMID- 16957153
TI  - Explaining and predicting preeclampsia.

PMID- 16957154
TI  - Risk of bleeding after elective percutaneous coronary intervention.

PMID- 16957155
TI  - Dasatinib in chronic myelogenous leukemia.

PMID- 16957156
TI  - Genomic diagnosis of Burkitt's lymphoma.

PMID- 16957157
TI  - Vitamins C and E and the prevention of preeclampsia.

PMID- 16957158
TI  - Measured and estimated glomerular filtration rate.

PMID- 16957159
TI  - Panic disorder.

PMID- 16957160
TI  - Hematopoietic stem-cell transplantation.

PMID- 16957161
TI  - Molecular profiling of a tumor of unknown origin.

PMID- 16957162
TI  - Fluorescence visualization of branchial collagen columns embraced by pillar
      cells.
AB  - A collagen column is a structure of the extracellular matrix that helps to
      maintain the flatness and width of gill lamella. Collagen columns are unique in
      that they are enfolded by plasma membrane of pillar cells that form two
      dimensional vascular networks between parallel sheets of respiratory epithelia.
      Despite their unique structure and fundamental importance in the physiology of
      aquatic animals, little is known about their properties and molecular components,
      owing to the lack of detection methods. In this study we demonstrated that
      collagen columns can be visualized by staining with fluorescence-labeled
      concanavalin A (ConA), a lectin that specifically recognizes the trimannoside
      core of N-glycosylated proteins and histidine-tagged green fluorescent protein
      (His(6)-Xpress-GFP), a fluorescent substrate for transglutaminase. We constructed
      a three-dimensional image of a pillar cell and visualized the spatial
      relationship between collagen columns and contractile apparatuses within the
      pillar cell body. This manuscript contains online supplemental material at
      (www.jhc.org). Please visit this article online to view these materials.

PMID- 16957163
TI  - In vivo functional analysis of polyglutamic acid domains in recombinant bone
      sialoprotein.
AB  - Bone sialoprotein (BSP) is an anionic phosphoprotein expressed in mineralizing
      connective tissues that binds to hydroxyapatite and nucleates its formation in
      vitro. Two polyglutamic acid regions (poly [E]) are believed to participate in
      these activities. The aim of this study was to evaluate the contribution of these
      acidic regions to the binding of prokaryote recombinant BSP (prBSP(E)) within an
      actual in vivo environment. Full-length prBSP(E) and prBSP(E) in which the poly
      [E] domains were replaced by polyalanine (prBSP(A)) were tagged with
      dinitrophenol (DNP). Tagged preparations comprised intact molecules and some
      fragmented forms. They were infused through a surgically created hole in the bone
      of rat hemimandibles and detected using immunogold labeling with anti-DNP
      antibodies. prBSP(E)-DNP was consistently immunodetected along exposed
      mineralized bone surfaces and osteocyte canaliculi at the surgical site. Few gold
      particles were observed on these surfaces when prBSP(A)-DNP was infused.
      Quantitative analyses showed significant differences in labeling between prBSP(E)
      DNP (5.04 +/- 0.73 particles/micro m2) and prBSP(A)-DNP (1.37 +/- 0.35
      particles/micro m2). These results indicate that poly [E] domains influence
      binding of prBSP(E) to surfaces presenting a mixture of mineral and proteins
      bathed by tissue fluids and suggest that they may similarly mediate the
      interaction of native BSP in the bone environment.

PMID- 16957165
TI  - Direct detection of herceptin/trastuzumab binding on breast tissue sections.
AB  - The protooncogene product HER-2/neu is the target of the humanized monoclonal
      antibody trastuzumab (Herceptin). Several tests are used clinically to identify
      patients with HER-2/neu overexpression based on evaluation by pathologists of
      gene amplification by fluorescence in situ hybridization or protein expression
      using immunohistochemistry (IHC). A simple technique has been developed for
      staining formalin-fixed, paraffin-embedded breast cancer tissue using unmodified
      Herceptin/trastuzumab as the primary antibody. Results were compared with
      staining with the commercial kit, HercepTest, as well as with polyclonal anti-HER
      2/neu antibodies and with biotinylated trastuzumab. These procedures were tested
      using four breast cancer microarrays. There were 854 cores that were stained with
      all four antibodies, representing 325 cases. A standard 4-point scoring system (0
      3) was used. A total of 156 cases (48%) were scored as 0 by all the methods used
      and 31 (9.5%) were positive (3+) by all methods. Of interest, three cases scored
      negative using polyclonal anti-HER-2/neu antibodies but were positive using
      unmodified trastuzumab. To clarify this discrepancy, whole sections of tumors
      were examined with both antibodies using double labeling. There were some tumors
      that demonstrated a mosaic pattern of staining with neighboring cells or groups
      of cells stained exclusively with one antibody or the other. These results
      demonstrate that unmodified humanized or human therapeutic antibodies could be
      used for preclinical testing or in a clinical laboratory setting for IHC-based
      selection of patients for treatment, and results of such selection could be
      different from those obtained using polyclonal antibody-based IHC procedure.

PMID- 16957164
TI  - Cellular localization of PRL-1 and PRL-2 gene expression in normal adult human
      tissues.
AB  - Recent evidence suggests that the PRL-1 and -2 phosphatases may be
      multifunctional enzymes with diverse roles in a variety of tissue and cell types.
      Northern blotting has previously shown widespread expression of both transcripts;
      however, little is known about the cell type-specific expression of either gene,
      especially in human tissues. Therefore, we investigated expression patterns for
      PRL-1 and -2 genes in multiple normal, adult human tissues using in situ
      hybridization. Although both transcripts were ubiquitously expressed, they
      exhibited strikingly different patterns of expression. PRL-2 was expressed
      heavily in almost every tissue and cell type examined, whereas PRL-1 expression
      levels varied considerably both between tissue types and between individuals.
      Widespread expression of PRL-1 and -2 in multiple organ systems suggests an
      important functional role for these enzymes in normal tissue homeostasis. In
      addition, the variable patterns of expression for these genes may provide
      distinct activities in each tissue or cell type.

PMID- 16957166
TI  - Analysis of protein expression in cell microarrays: a tool for antibody-based
      proteomics.
AB  - Tissue microarray (TMA) technology provides a possibility to explore protein
      expression patterns in a multitude of normal and disease tissues in a high
      throughput setting. Although TMAs have been used for analysis of tissue samples,
      robust methods for studying in vitro cultured cell lines and cell aspirates in a
      TMA format have been lacking. We have adopted a technique to homogeneously
      distribute cells in an agarose gel matrix, creating an artificial tissue. This
      enables simultaneous profiling of protein expression in suspension- and adherent
      grown cell samples assembled in a microarray. In addition, the present study
      provides an optimized strategy for the basic laboratory steps to efficiently
      produce TMAs. Presented modifications resulted in an improved quality of
      specimens and a higher section yield compared with standard TMA production
      protocols. Sections from the generated cell TMAs were tested for
      immunohistochemical staining properties using 20 well-characterized antibodies.
      Comparison of immunoreactivity in cultured dispersed cells and corresponding
      cells in tissue samples showed congruent results for all tested antibodies. We
      conclude that a modified TMA technique, including cell samples, provides a
      valuable tool for high-throughput analysis of protein expression, and that this
      technique can be used for global approaches to explore the human proteome.

PMID- 16957167
TI  - Lysosomal destabilization contributes to apoptosis of germinal center B
      lymphocytes.
AB  - During germinal center (GC) reactions, B-lymphocytes with high-affinity B-cell
      receptors are selected. Regulation of apoptosis is a key process in selecting
      such wanted B-cells and in eliminating B-cells with unwanted specificities. In
      this paper, we show that apoptosis in human GC B-cells involves lysosomal
      destabilization, which is strictly controlled by caspase-8 activity, but not by
      caspase-9 activity. Ligation of CD40 provides resistance to lysosomal
      destabilization. Experimental lysosomal rupture by the lysosomotropic drug O
      methyl-l-serine dodecylamide hydrochloride (MSDH) induces apoptosis in GC B
      cells, including phosphatidyl serine exposure, mitochondrial inactivation, and
      DNA fragmentation. These apoptotic features occur in the absence of caspase-3
      activity. Follicular dendritic cells (FDCs) protect binding B-lymphocytes from
      lysosomal destabilization, in both the absence and the presence of MSDH. Our
      study demonstrates that lysosomal leakage induces apoptosis of GC B-cells in a
      caspase-3-independent manner and that high-affinity binding to FDCsprevents
      lysosomal leakage and apoptosis in GC B-cells.

PMID- 16957168
TI  - Subcellular localization of CIAPIN1.
AB  - Cytokine-induced apoptosis inhibitor 1 (CIAPIN1) is a newly identified anti
      apoptotic molecule. Our previous studies have demonstrated that CIAPIN1 is
      ubiquitously expressed in normal fetal and adult human tissues and confers
      multidrug resistance in gastric cancer cells, possibly by upregulating the
      expression of multidrug resistance gene 1 and multidrug resistance-related
      protein 1. However, fundamental biological functions of CIAPIN1 have not been
      elucidated. In this study, we first predicted the subcellular localization of
      CIAPIN1 with bioinformatic approaches and then characterized the intracellular
      localization of CIAPIN1 in both human and mouse cells by a combination of
      techniques including (a)immunohistochemistry and immunofluorescence, (b) His
      tagged CIAPIN1 expression, and (c)subcellular fractionation and analysis of
      CIAPIN1 in the fractions by Western blotting. All methods produced consistent
      results; CIAPIN1 was localized in both the cytoplasm and the nucleus and was
      accumulated in the nucleolus. Bioinformatic prediction disclosed a putative
      nuclear localization signal and a putative nuclear export signal within both
      human and mouse CIAPIN1. These findings suggest that CIAPIN1 may undergo a
      cytoplasm-nucleus-nucleolus translocation.

PMID- 16957172
TI  - "Aren't I a victim?": Notes on identity challenges relating to police action in a
      mandatory arrest jurisdiction.
AB  - The mandated arrest of domestic violence perpetrators is a policy response to the
      problem of partner violence. Mandatory arrest can result, however, in unintended
      and sometimes undesirable arrest outcomes, including dual arrests (when both
      parties are arrested), retaliatory arrests (when the perpetrator has his or her
      partner wrongfully arrested), and failures to make an arrest (when one is
      warranted by law). Using an interactionist perspective, this research focuses on
      one negative effect of mandatory arrest: the identity challenge faced by female
      victims of domestic violence who experience undesirable arrest outcomes. The
      authors discuss policy implications, focusing on the potential empowerment
      effects of mandatory arrest.

PMID- 16957169
TI  - Spatial and temporal control of laminin-332 (5) and -511 (10) expression during
      induction of anagen hair growth.
AB  - Basement membrane plays important roles in hair growth. We characterized changes
      in laminin isoform expression during hair cycling. At the mRNA level, laminin-511
      (10) expression underwent a steady increase during anagen stages. In contrast,
      laminin-332 (5) expression was initially upregulated in outer root sheath (ORS)
      keratinocytes at anagen II and then transiently downregulated. Laminin-332
      significantly increased coincident with the signal in inner root sheath and hair
      matrix cells after anagen IV. Levels of laminin-332 proteins were also
      upregulated at late anagen I-III but dropped after anagen IV. This decrease
      coincided with increased levels of mRNA encoding the two proteases, membrane type
      1 metalloproteinase and bone morphogenetic protein 1, involved in laminin-332
      processing. Immunohistochemistry demonstrated that laminin-332 and alpha6 beta4
      integrin were well colocalized, but their signals were remarkably decreased in
      the lower half of follicles after anagen VI. Consistent with these data,
      ultrastructurally mature hemidesmosomes were seen in ORS keratinocytes at anagen
      II, whereas at anagen VI, only fragmental hemidesmosomes were present. In hair
      follicle culture, laminin-511 (10)/521 (11)-rich human placental laminin enhanced
      hair growth, whereas recombinant laminin-332 antagonized hair growth induced by
      laminin-511. Our results indicate a positive role for laminin-511 and a negative
      role for laminin-332 on hair growth.

PMID- 16957173
TI  - Intimate partner violence: predictors of recidivism in a sample of arrestees.
AB  - This article seeks to identify the variables that predict intimate partner
      violence recidivism. Neither prosecutorial actions, such as case rejection or
      subsequent dismissal, nor judicial imposition of jail terms or placement in a
      batterer treatment program demonstrated predictive value. Extralegal variables
      associated with the defendant, such as cohabitation status, marital status,
      gender, employment, and substance use at the time of the incident, all failed to
      attain significance. Victim support for arrest and prosecution were also
      unrelated to revictimization. Conversely, use of a weapon, the offender's prior
      arrest for any offense, and the presence of a protective order at the time of the
      precipitating incident all predicted rearrest for intimate violence within an 18
      month follow-up period. Policy implications are discussed.

PMID- 16957174
TI  - Victims of intimate partner violence more likely to report abuse from in-laws.
AB  - The current study of South Asians in the United States was designed to assess
      quantitatively the association between intimate partner violence (IPV) and
      emotional abuse by in-laws (n=169) and to qualitatively identify via in-depth
      interviews with battered women (n=23) forms of abuse perpetrated by in-laws.
      Quantitative findings demonstrate a significant relationship between IPV and
      abuse from in-laws (odds ratio=5.7, 95% confidence interval=1.5-21.5).
      Qualitative data demonstrate that abuse by in-laws includes emotional abuse
      (e.g., isolation, social and economic control, and domestic servitude), awareness
      or support of IPV, and direct physical abuse. Domestic violence interventions
      with South Asian women must consider abuse from in-laws and IPV experiences.

PMID- 16957175
TI  - Abusive partners and ex-partners: understanding the effects of relationship to
      the abuser on women's well-being.
AB  - This study examined how being abused by a current partner versus an ex-partner
      might affect psychological well-being and social support in a community sample of
      398 women, half of whom had experienced abuse in the past 6 months. The impact of
      emotional and physical abuse was influenced by partner status, with emotional
      abuse being more detrimental to women abused by current partners and physical
      abuse being more detrimental to women abused by ex-partners. Emotional support
      was negatively related to depression in women abused by current partners, whereas
      practical support was negatively related to depression in women abused by ex
      partners. The implications for interventions with abused women are discussed.

PMID- 16957176
TI  - Everyday sexism and posttraumatic stress disorder in women: a correlational
      study.
AB  - This study examined the correlations between everyday (nonviolent) sexism and the
      development of trauma symptoms in women. A total of 382 women completed a
      subjective measurement of the experience of sexism, a checklist of gender-based
      stressors (including acts of violence), a measurement of posttraumatic stress
      disorder (PTSD), and a demographic questionnaire. Results indicated a moderately
      strong relationship between the experience of everyday sexism and PTSD. A
      stepwise multiple regression revealed that when all variables (test scores,
      subscale scores, and demographic characteristics) were entered, the most
      predictive variable for trauma was recent sexist degradation, accounting for 20%
      of the variance in PTSD scores.

PMID- 16957178
TI  - Plant sterol or stanol esters retard lesion formation in LDL receptor-deficient
      mice independent of changes in serum plant sterols.
AB  - Statins do not always decrease coronary heart disease mortality, which was
      speculated based on increased serum plant sterols observed during statin
      treatment. To evaluate plant sterol atherogenicity, we fed low density
      lipoprotein-receptor deficient (LDLr(+/-)) mice for 35 weeks with Western diets
      (control) alone or enriched with atorvastatin or atorvastatin plus plant sterols
      or stanols. Atorvastatin decreased serum cholesterol by 22% and lesion area by
      57%. Adding plant sterols or stanols to atorvastatin decreased serum cholesterol
      by 39% and 41%. Cholesterol-standardized serum plant sterol concentrations
      increased by 4- to 11-fold during sterol plus atorvastatin treatment versus
      stanol plus atorvastatin treatment. However, lesion size decreased similarly in
      the sterol plus atorvastatin (-99% vs. control) and the stanol plus atorvastatin
      (-98%) groups, with comparable serum cholesterol levels, suggesting that
      increased plant sterol concentrations are not atherogenic. Our second study
      confirms this conclusion. Compared with lesions after a 33 week atherogenic
      period, lesion size further increased in controls (+97%) during 12 more weeks on
      the diet, whereas 12 weeks with the addition of plant sterols or stanols
      decreased lesion size (66% and 64%). These findings indicate that in LDLr(+/-)
      mice 1) increased cholesterol-standardized serum plant sterol concentrations are
      not atherogenic, 2) adding plant sterols/stanols to atorvastatin further inhibits
      lesion formation, and 3) plant sterols/stanols inhibit the progression or even
      induce the regression of existing lesions.

PMID- 16957179
TI  - Coordinated control of bile acids and lipogenesis through FXR-dependent
      regulation of fatty acid synthase.
AB  - We discovered a nuclear receptor element in the FAS promoter consisting of an
      inverted repeat spaced by one nucleotide (IR-1) and located 21 bases downstream
      of a direct repeat sequenced by 4 nucleotides (DR-4) oxysterol liver X receptor
      response element. An IR-1 is present in promoters of several genes of bile acid
      and lipid homeostasis and binds farnesoid X receptor/retinoid X receptor
      (FXR/RXR) heterodimers to mediate bile acid-dependent transcription. We show that
      FXR/RXRalpha specifically binds to the FAS IR-1 and that the FAS promoter is
      activated approximately 10-fold by the addition of a synthetic FXR agonist in
      transient transfection assays. We also demonstrate that endogenous FXR binds
      directly to the murine FAS promoter in the hepatic genome using a tissue-based
      chromatin immunoprecipitation procedure. Furthermore, we show that feeding wild
      type mice a chow diet supplemented with the natural FXR agonist chenodeoxycholic
      acid results in a significant induction of FAS mRNA expression. Thus, we have
      identified a novel IR-1 in the FAS promoter and demonstrate that it mediates
      FXR/bile acid regulation of the FAS gene. These findings provide the first
      evidence for direct regulation of lipogenesis by bile acids and also provide a
      mechanistic rationale for previously unexplained observations regarding bile acid
      control of FAS expression.

PMID- 16957180
TI  - Biochemical and structural comparative study between bird and mammal pancreatic
      colipases.
AB  - Three colipases were purified from pancreas of two birds (ostrich and turkey) and
      one mammal (dromedary). After acidic and/or heat treatment and precipitation by
      sulfate ammonium and then ethanol, cofactors were purified by Sephadex G-50 gel
      filtration followed by ion-exchange chromatography first on Mono S and then on
      Mono Q. One molecular form was obtained from each species with a molecular mass
      of approximately 10 kDa. Cofactors were not glycosylated. The N-terminal
      sequences of the three purified cofactors showed high sequence homology. A 90
      amino acid sequence of the ostrich cofactor was established based on peptide
      sequences from four different digests of the denaturated protein using trypsin,
      chymotrypsin, thermolysin, or staphylococcal protease. This sequence exhibited a
      high degree of homology with chicken and mammal cofactors. Bile salt-inhibited
      pancreatic lipases from five species were activated to variable extents by
      colipases from bird and mammal origins. The bird pancreatic lipase-colipase
      system appears to be functionally similar to homologous lipolytic systems from
      higher mammals. Our comparative study showed that mammal colipase presents a
      lower activation level toward bird lipases than the bird counterpart. Three
      dimensional modeling of ostrich colipase suggested a structural explanation of
      this fact.

PMID- 16957181
TI  - Upregulation of liver VLDL receptor and FAT/CD36 expression in LDLR-/-
      apoB100/100 mice fed trans-10,cis-12 conjugated linoleic acid.
AB  - This study explores the mechanisms responsible for the fatty liver setup in mice
      fed trans-10,cis-12 conjugated linoleic acid (t10c12 CLA), hypothesizing that an
      induction of low density lipoprotein receptor (LDLR) expression is associated
      with lipid accumulation. To this end, the effects of t10c12 CLA treatment on
      lipid parameters, serum lipoproteins, and expression of liver lipid receptors
      were measured in LDLR(-/-) apoB(100/100) mice as a model of human familial
      hypercholesterolemia itself depleted of LDLR. Mice were fed t10c12 CLA over 2 or
      4 weeks. We first observed that the treatment induced liver steatosis, even in
      the absence of LDLR. Mice treated for 2 weeks exhibited hypertriglyceridemia with
      high levels of VLDL and HDL, whereas a 4 week treatment inversely induced a
      reduction of serum triglycerides (TGs), essentially through a decrease in VLDL
      levels. In the absence of LDLR, the mRNA levels of other proteins, such as VLDL
      receptor, lipoprotein lipase, and fatty acid translocase, usually not expressed
      in the liver, were upregulated, suggesting their involvement in the steatosis
      setup and lipoprotein clearance. The data also suggest that the TG-lowering
      effect induced by t10c12 CLA treatment was attributable to both the reduction of
      circulating free fatty acids in response to the severe lipoatrophy and the high
      capacity of liver to clear off plasma lipids.

PMID- 16957182
TI  - Stability and change in estuarine biofilm bacterial community diversity.
AB  - Biofouling communities contribute significantly to aquatic ecosystem productivity
      and biogeochemical cycling. Our knowledge of the distribution, composition, and
      activities of these microbially dominated communities is limited compared to
      other components of estuarine ecosystems. This study investigated the temporal
      stability and change of the dominant phylogenetic groups of the domain Bacteria
      in estuarine biofilm communities. Glass slides were deployed monthly over 1 year
      for 7-day incubations during peak tidal periods in East Sabine Bay, Fla.
      Community profiling was achieved by using 16S rRNA genes and terminal restriction
      fragment length polymorphism (T-RFLP) of 16S rRNA genes in combination with
      ribotyping, cloning, and sequencing to evaluate diversity and to identify
      dominant microorganisms. Bacterial community profiles from biofilms grown near
      the benthos showed distinct periods of constancy within winter and summer
      sampling periods. Similar periods of stability were also seen in T-RFLP patterns
      from floating biofilms. Alternating dominance of phylogenetic groups between
      seasons appeared to be associated with seasonal changes in temperature, nutrient
      availability, and light. The community structure appeared to be stable during
      these periods despite changes in salinity and in dissolved oxygen.

PMID- 16957183
TI  - Microbial community diversity associated with carbon and nitrogen cycling in
      permeable shelf sediments.
AB  - Though a large fraction of primary production and organic matter cycling in the
      oceans occurs on continental shelves dominated by sandy deposits, the microbial
      communities associated with permeable shelf sediments remain poorly
      characterized. Therefore, in this study, we provide the first detailed
      characterization of microbial diversity in marine sands of the South Atlantic
      Bight through parallel analyses of small-subunit (SSU) rRNA gene (Bacteria), nosZ
      (denitrifying bacteria), and amoA (ammonia-oxidizing bacteria) sequences.
      Communities were analyzed by parallel DNA extractions and clone library
      construction from both sediment core material and manipulated sediment within
      column experiments designed for geochemical rate determinations. Rapid organic
      matter degradation and coupled nitrification-denitrification were observed in
      column experiments at flow rates resembling in situ conditions over a range of
      oxygen concentrations. Numerous SSU rRNA phylotypes were affiliated with the
      phyla Proteobacteria (classes Alpha-, Delta-, and Gammaproteobacteria),
      Planctomycetes, Cyanobacteria, Chloroflexi, and Bacteroidetes. Detectable
      sequence diversity of nosZ and SSU rRNA genes increased in stratified redox
      stabilized columns compared to in situ sediments, with the Alphaproteobacteria
      comprising the most frequently detected group. Alternatively, nitrifier
      communities showed a relatively low and stable diversity that did not covary with
      the other gene targets. Our results elucidate predominant phylotypes that are
      likely to catalyze carbon and nitrogen cycling in marine sands. Although overall
      diversity increased in response to redox stabilization and stratification in
      column experiments, the major phylotypes remained the same in all of our
      libraries, indicating that the columns sufficiently mimic in situ conditions.

PMID- 16957184
TI  - Biological filtration limits carbon availability and affects downstream biofilm
      formation and community structure.
AB  - Carbon removal strategies have gained popularity in the mitigation of biofouling
      in water reuse processes, but current biofilm-monitoring practices based on
      organic-carbon concentrations may not provide an accurate representation of the
      in situ biofilm problem. This study evaluated a submerged microtiter plate assay
      for direct and rapid monitoring of biofilm formation by subjecting the plates to
      a continuous flow of either secondary effluent (SE) or biofilter-treated
      secondary effluent (BF). This method was very robust, based on a high correlation
      (R(2) = 0.92) between the biomass (given by the A(600) in the microtiter plate
      assay) and the biovolume (determined from independent biofilms developed on glass
      slides under identical conditions) measurements, and revealed that the biomasses
      in BF biofilms were consistently lower than those in SE biofilms. The influence
      of the organic-carbon content on the biofilm community composition and succession
      was further evaluated using molecular tools. Terminal restriction fragment length
      polymorphism analysis of 16S rRNA genes revealed a group of pioneer colonizers,
      possibly represented by Sphingomonadaceae and Caulobacter organisms, to be common
      in both SE and BF biofilms. However, differences in organic-carbon availabilities
      in the two water samples eventually led to the selection of distinct biofilm
      communities. Alphaproteobacterial populations were confirmed by fluorescence in
      situ hybridization to be enriched in SE biofilms, while Betaproteobacteria were
      dominant in BF biofilms. Cloning analyses further demonstrated that
      microorganisms adapted for survival under low-substrate conditions (e.g.,
      Aquabacterium, Caulobacter, and Legionella) were preferentially selected in the
      BF biofilm, suggesting that carbon limitation strategies may not achieve adequate
      biofouling control in the long run.

PMID- 16957185
TI  - Identification of a diagnostic marker to detect freshwater cyanophages of
      filamentous cyanobacteria.
AB  - Cyanophages are viruses that infect the cyanobacteria, globally important
      photosynthetic microorganisms. Cyanophages are considered significant components
      of microbial communities, playing major roles in influencing host community
      diversity and primary productivity, terminating cyanobacterial water blooms, and
      influencing biogeochemical cycles. Cyanophages are ubiquitous in both marine and
      freshwater systems; however, the majority of molecular research has been biased
      toward the study of marine cyanophages. In this study, a diagnostic probe was
      developed to detect freshwater cyanophages in natural waters. Oligonucleotide PCR
      based primers were designed to specifically amplify the major capsid protein gene
      from previously characterized freshwater cyanomyoviruses that are infectious to
      the filamentous, nitrogen-fixing cyanobacterial genera Anabaena and Nostoc. The
      primers were also successful in yielding PCR products from mixed virus
      communities concentrated from water samples collected from freshwater lakes in
      the United Kingdom. The probes are thought to provide a useful tool for the
      investigation of cyanophage diversity in freshwater environments.

PMID- 16957186
TI  - Haloalkane dehalogenase LinB is responsible for beta- and delta
      hexachlorocyclohexane transformation in Sphingobium indicum B90A.
AB  - Incubation of resting cells of Sphingobium indicum B90A, Sphingobium japonicum
      UT26, and Sphingobium francense Sp+ showed that they were able to transform beta-
      and delta-hexachlorocyclohexane (beta- and delta-HCH, respectively), the most
      recalcitrant hexachlorocyclohexane isomers, to pentachlorocyclohexanols, but only
      resting cells of strain B90A could further transform the pentachlorocyclohexanol
      intermediates to the corresponding tetrachlorocyclohexanediols. Moreover,
      experiments with resting cells of Escherichia coli expressing the LinB proteins
      of strains B90A, UT26, and Sp+ indicated that LinB was responsible for these
      transformations. Purified LinB proteins from all three strains also effected the
      formation of the respective pentachlorocyclohexanols. Although the three LinB
      enzymes differ only marginally with respect to amino acid sequence, they showed
      interesting differences with respect to substrate specificity. When LinB from
      strain B90A was incubated with beta- and delta-HCH, the pentachlorocyclohexanol
      products were further transformed and eventually disappeared from the incubation
      mixtures. In contrast, the LinB proteins from strains UT26 and Sp+ could not
      catalyze transformation of the pentachlorocyclohexanols, and these products
      accumulated in the incubation mixture. A mutant of strain Sp+ lacking linA and
      linB did not degrade any of the HCH isomers, including beta-HCH, and
      complementation of this mutant by linB from strain B90A restored the ability to
      degrade beta- and delta-HCH.

PMID- 16957187
TI  - Diversity of telomere palindromic sequences and replication genes among
      Streptomyces linear plasmids.
AB  - Streptomyces sp. linear plasmids and linear chromosomes usually contain conserved
      terminal palindromic sequences bound by the conserved telomeric proteins Tap and
      Tp, encoded by the tap and tpg genes, respectively, as well as plasmid loci
      required for DNA replication in circular mode when the telomeres are deleted.
      These consist of iterons and an adjacent rep gene. By using PCR, we found that 8
      of 17 newly detected linear plasmids in Streptomyces strains lack typical
      telomeric tap and tpg sequences. Instead, two novel telomeres in plasmids pRL1
      and pRL2 from the eight strains and one conserved telomere in pFRL1 from the
      other strains were identified, while multiple short palindromes were also found
      in the plasmids. The complete nucleotide sequence of pRL2 revealed a gene
      encoding a protein containing two domains, resembling Tap of Streptomyces and a
      helicase of Thiobacillus, and an adjacent gene encoding a protein similar to Tpg
      of Streptomyces and a portion of the telomere terminal protein pTP of
      adenoviruses. No typical iterons-rep loci were found in the three plasmids. These
      results indicate an unexpected diversity of telomere palindromic sequences and
      replication genes among Streptomyces linear plasmids.

PMID- 16957188
TI  - New screening software shows that most recent large 16S rRNA gene clone libraries
      contain chimeras.
AB  - A new computer program, called Mallard, is presented for screening entire 16S
      rRNA gene libraries of up to 1,000 sequences for chimeras and other artifacts.
      Written in the Java computer language and capable of running on all major
      operating systems, the program provides a novel graphical approach for
      visualizing phylogenetic relationships among 16S rRNA gene sequences. To
      illustrate its use, we analyzed most of the large libraries of cloned bacterial
      16S rRNA gene sequences submitted to the public repository during 2005. Defining
      a large library as one containing 100 or more sequences of 1,200 bases or
      greater, we screened 25 of the 28 libraries and found that all but three
      contained substantial anomalies. Overall, 543 anomalous sequences were found. The
      average anomaly content per clone library was 9.0%, 4% higher than that
      previously estimated for the public repository overall. In addition, 90.8% of
      anomalies had characteristic chimeric patterns, a rise of 25.4% over that found
      previously. One library alone was found to contain 54 chimeras, representing
      45.8% of its content. These figures far exceed previous estimates of artifacts
      within public repositories and further highlight the urgent need for all
      researchers to adequately screen their libraries prior to submission. Mallard is
      freely available from our website at
      http://www.cardiff.ac.uk/biosi/research/biosoft/.

PMID- 16957189
TI  - Fiber-optic microarray for simultaneous detection of multiple harmful algal bloom
      species.
AB  - Harmful algal blooms (HABs) are a serious threat to coastal resources, causing a
      variety of impacts on public health, regional economies, and ecosystems. Plankton
      analysis is a valuable component of many HAB monitoring and research programs,
      but the diversity of plankton poses a problem in discriminating toxic from
      nontoxic species using conventional detection methods. Here we describe a
      sensitive and specific sandwich hybridization assay that combines fiber-optic
      microarrays with oligonucleotide probes to detect and enumerate the HAB species
      Alexandrium fundyense, Alexandrium ostenfeldii, and Pseudo-nitzschia australis.
      Microarrays were prepared by loading oligonucleotide probe-coupled microspheres
      (diameter, 3 mum) onto the distal ends of chemically etched imaging fiber
      bundles. Hybridization of target rRNA from HAB cells to immobilized probes on the
      microspheres was visualized using Cy3-labeled secondary probes in a sandwich-type
      assay format. We applied these microarrays to the detection and enumeration of
      HAB cells in both cultured and field samples. Our study demonstrated a detection
      limit of approximately 5 cells for all three target organisms within 45 min,
      without a separate amplification step, in both sample types. We also developed a
      multiplexed microarray to detect the three HAB species simultaneously, which
      successfully detected the target organisms, alone and in combination, without
      cross-reactivity. Our study suggests that fiber-optic microarrays can be used for
      rapid and sensitive detection and potential enumeration of HAB species in the
      environment.

PMID- 16957190
TI  - Quantitative detection of the free-living amoeba Hartmannella vermiformis in
      surface water by using real-time PCR.
AB  - A real-time PCR-based method targeting the 18S rRNA gene was developed for the
      quantitative detection of Hartmannella vermiformis, a free-living amoeba which is
      a potential host for Legionella pneumophila in warm water systems and cooling
      towers. The detection specificity was validated using genomic DNA of the closely
      related amoeba Hartmannella abertawensis as a negative control and sequence
      analysis of amplified products from environmental samples. Real-time PCR
      detection of serially diluted DNA extracted from H. vermiformis was linear for
      microscopic cell counts between 1.14 x 10(-1) and 1.14 x 10(4) cells per PCR. The
      genome of H. vermiformis harbors multiple copies of the 18S rRNA gene, and an
      average number (with standard error) of 1,330 +/- 127 copies per cell was derived
      from real-time PCR calibration curves for cell suspensions and plasmid DNA. No
      significant differences were observed between the 18S rRNA gene copy numbers for
      trophozoites and cysts of strain ATCC 50237 or between the copy numbers for this
      strain and strain KWR-1. The developed method was applied to water samples (200
      ml) collected from a variety of lakes and rivers serving as sources for drinking
      water production in The Netherlands. Detectable populations were found in 21 of
      the 28 samples, with concentrations ranging from 5 to 75 cells/liter. A high
      degree of similarity (> or =98%) was observed between sequences of clones
      originating from the different surface waters and between these clones and the
      reference strains. Hence, H. vermiformis, which is highly similar to strains
      serving as hosts for L. pneumophila, is a common component of the microbial
      community in fresh surface water.

PMID- 16957191
TI  - Transcriptional organization and regulation of magnetosome operons in
      Magnetospirillum gryphiswaldense.
AB  - Genes involved in magnetite biomineralization are clustered within the genomic
      magnetosome island of Magnetospirillum gryphiswaldense. Their transcriptional
      organization and regulation were studied by several approaches. Cotranscription
      of genes within the mamAB, mamDC, and mms clusters was demonstrated by reverse
      transcription-PCR (RT-PCR) of intergenic regions, indicating the presence of long
      polycistronic transcripts extending over more than 16 kb. The transcription start
      points of the mamAB, mamDC, and mms operons were mapped at 22 bp, 52 bp, and 58
      bp upstream of the first genes of the operons, respectively. Identified -10 and 
      35 boxes of the P(mamAB), P(mamDC), and P(mms) promoters showed high similarity
      to the canonical sigma(70) recognition sequence. The transcription of magnetosome
      genes was further studied in response to iron and oxygen. Transcripts of
      magnetosome genes were detected by RT-PCR both in magnetic cells grown
      microaerobically under iron-sufficient conditions and in nonmagnetic cells grown
      either aerobically or with iron limitation. The presence of transcripts was found
      to be independent of the growth phase. Further results from partial RNA
      microarrays targeting the putative magnetosome transcriptome of M.
      gryphiswaldense and real-time RT-PCR experiments indicated differences in
      expression levels depending on growth conditions. The expression of the mam and
      mms genes was down-regulated in nonmagnetic cells under iron limitation and, to a
      lesser extent, during aerobic growth compared to that in magnetite-forming cells
      grown microaerobically under iron-sufficient conditions.

PMID- 16957192
TI  - Tick-borne rickettsial pathogens in ticks and small mammals in Korea.
AB  - In order to investigate the prevalence of tick-borne infectious agents among
      ticks, ticks comprising five species from two genera (Hemaphysalis spp. and
      Ixodes spp.) were screened using molecular techniques. Ticks (3,135) were
      collected from small wild-caught mammals or by dragging/flagging in the Republic
      of Korea (ROK) and were pooled into a total of 1,638 samples (1 to 27 ticks per
      pool). From the 1,638 tick samples, species-specific fragments of Anaplasma
      phagocytophilum (1 sample), Anaplasma platys (52 samples), Ehrlichia chaffeensis
      (29 samples), Ehrlichia ewingii (2 samples), Ehrlichia canis (18 samples), and
      Rickettsia rickettsii (28 samples) were amplified by PCR assay. Twenty-one pooled
      and individual tick samples had mixed infections of two (15 samples) or three (6
      samples) pathogens. In addition, 424 spleen samples from small captured mammals
      (389 rodents, 33 insectivores, and 2 weasels) were screened for selected zoonotic
      pathogens. Species-specific DNA fragments of A. phagocytophilum (110 samples), A.
      platys (68 samples), E. chaffeensis (8 samples), E. ewingii (26 samples), E.
      canis (51 samples), and Rickettsia sp. (22 samples) were amplified by PCR assay.
      One hundred thirty small mammals had single infections, while 4, 14, and 21
      striped field mice (Apodemus agrarius) had mixed infections of four, three, and
      two pathogens, respectively. Phylogenetic analysis based on nucleotide sequence
      comparison also revealed that Korean strains of E. chaffeensis clustered closely
      with those from China and the United States, while the Rickettsia (rOmpA)
      sequences clustered within a clade together with a Chinese strain. These results
      suggest that these agents should be considered in differential diagnosis while
      examining cases of acute febrile illnesses in humans as well as animals in the
      ROK.

PMID- 16957193
TI  - Survival of Salmonella enterica serovar Newport in manure and manure-amended
      soils.
AB  - Salmonella enterica serovar Newport has undergone a rapid epidemic spread in
      dairy cattle. This provides an efficient mechanism for pathogen amplification and
      dissemination into the environment through manure spreading on agricultural land.
      The objective of this study was to determine the survival characteristics of
      Salmonella serovar Newport in manure and manure-amended soils where the pathogen
      may be amplified. A multidrug-resistant (MDR) Salmonella serovar Newport strain
      and a drug-susceptible (DS) strain, both bovine isolates, were inoculated into
      dairy manure that was incubated under constant temperature and moisture
      conditions alone or after being mixed with sterilized or nonsterilized soil.
      Salmonella serovar Newport concentrations increased by up to 400% in the first 1
      to 3 days following inoculation, and a trend of steady decline followed. With
      manure treatment, a sharp decline in cell concentration occurred after day 35,
      possibly due to microbial antagonism. For all treatments, decreases in Salmonella
      serovar Newport concentrations over time fit a first-order kinetic model. Log
      reduction time was 14 to 32 days for 1 log(10), 28 to 64 days for 2 log(10), and
      42 to 96 days for 3 log(10) declines in the organisms' populations from initially
      inoculated concentrations. Most-probable-number monitoring data indicated that
      the organisms persisted for 184, 332, and 405 days in manure, manure-amended
      nonsterilized soil, and manure-amended sterilized soil, respectively. The MDR
      strain and the DS strain had similar survival patterns.

PMID- 16957194
TI  - Copper resistance in Enterococcus faecium, mediated by the tcrB gene, is selected
      by supplementation of pig feed with copper sulfate.
AB  - The tcr gene cluster mediates in vitro copper resistance in Enterococcus faecium.
      Here we describe the selection of tcr-mediated copper resistance in E. faecium in
      an animal feeding experiment with young pigs fed 175 mg copper/kg feed (ppm),
      which is the concentration commonly used for piglets in European pig production.
      tcr-mediated copper resistance was not selected for in a control group fed low
      levels of copper (6 ppm). We also show coselection of macrolide- and glycopeptide
      resistant E. faecium in the animal group fed the high level of copper. Finally,
      we identify the tcr genes in the enterococcal species E. mundtii, E.
      casseliflavus, and E. gallinarum for the first time.

PMID- 16957195
TI  - Transformation of the antibacterial agent norfloxacin by environmental
      mycobacteria.
AB  - Because fluoroquinolone antimicrobial agents may be released into the
      environment, the potential for environmental bacteria to biotransform these drugs
      was investigated. Eight Mycobacterium sp. cultures in a sorbitol-yeast extract
      medium were dosed with 100 microg ml(-1) of norfloxacin and incubated for 7 days.
      The MICs of norfloxacin for these strains, tested by an agar dilution method,
      were 1.6 to 25 microg ml(-1). Cultures were extracted with ethyl acetate, and
      potential metabolites in the extracts were purified by high-performance liquid
      chromatography. The metabolites were identified using mass spectrometry and
      nuclear magnetic resonance spectroscopy. N-Acetylnorfloxacin (5 to 50% of the
      total absorbance at 280 nm) was produced by the eight Mycobacterium strains. N
      Nitrosonorfloxacin (5 to 30% of the total absorbance) was also produced by
      Mycobacterium sp. strain PYR100 and Mycobacterium gilvum PYR-GCK. The MICs of N
      nitrosonorfloxacin and N-acetylnorfloxacin were 2- to 38- and 4- to 1,000-fold
      higher, respectively, than those of norfloxacin for several different bacteria,
      including the two strains that produced both metabolites. Although N
      nitrosonorfloxacin had less antibacterial activity, nitrosamines are potentially
      carcinogenic. The biotransformation of fluoroquinolones by mycobacteria may serve
      as a resistance mechanism.

PMID- 16957196
TI  - Lack of evidence for vertical transmission of Campylobacter spp. in chickens.
AB  - Campylobacter jejuni is a major cause of bacterial food-borne infection in the
      industrial world. There is evidence that C. jejuni is present in eggs and
      hatchery fluff, opening the possibility for vertical transmission from hens to
      progeny. Poultry operations in Iceland provide an excellent opportunity to study
      this possibility, since breeding flocks are established solely from eggs imported
      from grandparent flocks in Sweden. This leaves limited opportunity for
      grandparents and their progeny to share isolates through horizontal transmission.
      While Campylobacter was not detected in all grandparent flocks, 13 of the 16 egg
      import lots consisted of eggs gathered from one or more Campylobacter-positive
      grandparent flocks. No evidence of Campylobacter was found by PCR in any of the
      10 relevant quarantine hatchery fluff samples examined, and no Campylobacter was
      isolated from the parent birds through 8 weeks, while they were still in
      quarantine rearing facilities. After the birds were moved to less biosecure
      rearing facilities, Campylobacter was isolated, and 29 alleles were observed
      among the 224 isolates studied. While three alleles were found in both Sweden and
      Iceland, in no case was the same allele found both in a particular grandparent
      flock and in its progeny. We could find no evidence for vertical transmission of
      Campylobacter to the approximately 60,000 progeny parent breeders that were
      hatched from eggs coming from Campylobacter-positive grandparent flocks. If
      vertical transmission is occurring, it is not a significant source for the
      contamination of chicken flocks with Campylobacter spp.

PMID- 16957197
TI  - Selecting lactic acid bacteria for their safety and functionality by use of a
      mouse colitis model.
AB  - Studies showed that specific probiotics might provide therapeutic benefits in
      inflammatory bowel disease. However, a rigorous screening of new probiotics is
      needed to study possible adverse interactions with the host, particularly when
      intended for administration to individuals with certain health risks. In this
      context, the objective of this study was to investigate the role of three
      lactobacilli (LAB) on intestinal inflammation and bacterial translocation using
      variations of the mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)
      induced acute colitis. We first compared the in vitro ability of LAB to survive
      gastrointestinal tract (GIT) conditions and their ability to persist in the GIT
      of mice following daily oral administration. As a control, we included a
      nonprobiotic Lactobacillus paracasei strain, previously isolated from an
      endocarditis patient. Feeding high doses of LAB strains to healthy and to TNBS
      treated mice did not induce any detrimental effect or abnormal translocation of
      the bacteria. Oral administration of Lactobacillus salivarius Ls-33 had a
      significant preventive effect on colitis in mice, while Lactobacillus plantarum
      Lp-115 and Lactobacillus acidophilus NCFM did not. None of the three selected LAB
      strains translocated to extraintestinal organs of TNBS-treated mice. In contrast,
      L. paracasei exacerbated colitis under severe inflammatory conditions and
      translocated to extraintestinal organs. This study showed that evaluations of the
      safety and functionality of new probiotics are recommended. We conclude that not
      all lactobacilli have similar effects on intestinal inflammation and that
      selected probiotics such as L. salivarius Ls-33 may be considered in the
      prevention or treatment of intestinal inflammation.

PMID- 16957198
TI  - Effect of natural sunlight on bacterial activity and differential sensitivity of
      natural bacterioplankton groups in northwestern Mediterranean coastal waters.
AB  - We studied the effects of natural sunlight on heterotrophic marine
      bacterioplankton in short-term experiments. We used a single-cell level approach
      involving flow cytometry combined with physiological probes and
      microautoradiography to determine sunlight effects on the activity and integrity
      of the cells. After 4 h of sunlight exposure, most bacterial cells maintained
      membrane integrity and viability as assessed by the simultaneous staining with
      propidium iodide and SYBR green I. In contrast, a significant inhibition of
      heterotrophic bacterial activity was detected, measured by 5-cyano-2,3 ditolyl
      tetrazolium chloride reduction and leucine incorporation. We applied
      microautoradiography combined with catalyzed reporter deposition-fluorescence in
      situ hybridization to test the sensitivity of the different bacterial groups
      naturally occurring in the Northwestern Mediterranean to sunlight. Members of the
      Gammaproteobacteria and Bacteroidetes groups appeared to be highly resistant to
      solar radiation, with small changes in activity after exposure. On the contrary,
      Alphaproteobacteria bacteria were more sensitive to radiation as measured by the
      cell-specific incorporation of labeled amino acids, leucine, and ATP. Within
      Alphaproteobacteria, bacteria belonging to the Roseobacter group showed higher
      resistance than members of the SAR11 cluster. The activity of Roseobacter was
      stimulated by exposure to photosynthetic available radiation compared to the dark
      treatment. Our results suggest that UV radiation can significantly affect the in
      situ single-cell activity of bacterioplankton and that naturally dominating
      phylogenetic bacterial groups have different sensitivity to natural levels of
      incident solar radiation.

PMID- 16957199
TI  - Purification, characterization, and gene sequence of michiganin A, an actagardine
      like lantibiotic produced by the tomato pathogen Clavibacter michiganensis subsp.
      michiganensis.
AB  - Members of the actinomycete genus Clavibacter are known to produce antimicrobial
      compounds, but so far none of these compounds has been purified and
      characterized. We have isolated an antimicrobial peptide, michiganin A, from the
      tomato pathogen Clavibacter michiganensis subsp. michiganensis, using ammonium
      sulfate precipitation followed by cation-exchange and reversed-phase
      chromatography steps. Upon chemical derivatization of putative dehydrated amino
      acids and lanthionine bridges by alkaline ethanethiol, Edman degradation yielded
      sequence information that proved to be sufficient for cloning of the gene by a
      genome-walking strategy. The mature unmodified peptide consists of 21 amino
      acids, SSSGWLCTLTIECGTIICACR. All of the threonine residues undergo dehydration,
      and three of them interact with cysteines via thioether bonds to form
      methyllanthionine bridges. Michiganin A resembles actagardine, a type B
      lantibiotic with a known three-dimensional structure, produced by Actinoplanes
      liguriae, which is a filamentous actinomycete. The DNA sequence of the gene
      showed that the michiganin A precursor contains an unusual putative signal
      peptide with no similarity to well-known secretion signals and only very limited
      similarity to the (only two) available leader peptides of other type B
      lantibiotics. Michiganin A inhibits the growth of Clavibacter michiganensis
      subsp. sepedonicus, the causal agent of ring rot of potatoes, with MICs in the
      low nanomolar range. Thus, michiganin A may have some potential in biological
      control of potato ring rot.

PMID- 16957200
TI  - Engineering a Saccharomyces cerevisiae wine yeast that exhibits reduced ethanol
      production during fermentation under controlled microoxygenation conditions.
AB  - We recently showed that expressing an H(2)O-NADH oxidase in Saccharomyces
      cerevisiae drastically reduces the intracellular NADH concentration and
      substantially alters the distribution of metabolic fluxes in the cell. Although
      the engineered strain produces a reduced amount of ethanol, a high level of
      acetaldehyde accumulates early in the process (1 g/liter), impairing growth and
      fermentation performance. To overcome these undesirable effects, we carried out a
      comprehensive analysis of the impact of oxygen on the metabolic network of the
      same NADH oxidase-expressing strain. While reducing the oxygen transfer rate led
      to a gradual recovery of the growth and fermentation performance, its impact on
      the ethanol yield was negligible. In contrast, supplying oxygen only during the
      stationary phase resulted in a 7% reduction in the ethanol yield, but without
      affecting growth and fermentation. This approach thus represents an effective
      strategy for producing wine with reduced levels of alcohol. Importantly, our data
      also point to a significant role for NAD(+) reoxidation in controlling the
      glycolytic flux, indicating that engineered yeast strains expressing an NADH
      oxidase can be used as a powerful tool for gaining insight into redox metabolism
      in yeast.

PMID- 16957201
TI  - Mutational and functional analysis of the beta-carotene ketolase involved in the
      production of canthaxanthin and astaxanthin.
AB  - Biosynthesis of the commercial carotenoids canthaxanthin and astaxanthin requires
      beta-carotene ketolase. The functional importance of the conserved amino acid
      residues of this enzyme from Paracoccus sp. strain N81106 (formerly classified as
      Agrobacterium aurantiacum) was analyzed by alanine-scanning mutagenesis.
      Mutations in the three highly conserved histidine motifs involved in iron
      coordination abolished its ability to catalyze the formation of ketocarotenoids.
      This supports the hypothesis that the CrtW ketolase belongs to the family of iron
      dependent integral membrane proteins. Most of the mutations generated at other
      highly conserved residues resulted in partial activity. All partially active
      mutants showed a higher amount of adonixanthin accumulation than did the wild
      type when expressed in Escherichia coli cells harboring the zeaxanthin
      biosynthetic gene cluster. Some of the partially active mutants also produced a
      significant amount of echinenone when expressed in cells producing beta-carotene.
      In fact, expression of a mutant carrying D117A resulted in the accumulation of
      echinenone as the predominant carotenoid. These observations indicate that
      partial inactivation of the CrtW ketolase can often lead to the production of
      monoketolated intermediates. In order to improve the conversion rate of
      astaxanthin catalyzed by the CrtW ketolase, a color screening system was
      developed. Three randomly generated mutants, carrying L175M, M99V, and M99I, were
      identified to have improved activity. These mutants are potentially useful in
      pathway engineering for the production of astaxanthin.

PMID- 16957202
TI  - Distinct bacterial communities exist beneath a high Arctic polythermal glacier.
AB  - Bacterial communities reside in basal ice, sediment, and meltwater in the supra-,
      sub-, and proglacial environments of John Evans Glacier, Nunavut, Canada. We
      examined whether the subglacial bacterial community shares common members with
      the pro- and supraglacial communities, and by inference, whether it could be
      derived from communities in either of these environments (e.g., by ice overriding
      proglacial sediments or by in-wash of surface meltwaters). Terminal restriction
      fragment length polymorphism analysis of bacterial 16S rRNA genes amplified from
      these environments revealed that the subglacial water, basal ice, and sediment
      communities were distinct from those detected in supraglacial meltwater and
      proglacial sediments, with 60 of 142 unique terminal restriction fragments (T
      RFs) detected exclusively in subglacial samples and only 8 T-RFs detected in all
      three environments. Supraglacial waters shared some T-RFs with subglacial water
      and ice, likely reflecting the seasonal flow of surface meltwater into the
      subglacial drainage system, whereas supraglacial and proglacial communities
      shared the fewest T-RFs. Thus, the subglacial community at John Evans Glacier
      appears to be predominantly autochthonous rather than allochthonous, and it may
      be adapted to subglacial conditions. Chemical analysis of water and melted ice
      also revealed differences between the supraglacial and proglacial environments,
      particularly regarding electrical conductivity and nitrate, sulfate, and
      dissolved organic carbon concentrations. Whereas the potential exists for common
      bacterial types to be broadly distributed throughout the glacial system, we have
      observed distinct bacterial communities in physically and chemically different
      glacial environments.

PMID- 16957203
TI  - Attachment of and biofilm formation by Enterobacter sakazakii on stainless steel
      and enteral feeding tubes.
AB  - Enterobacter sakazakii has been reported to form biofilms, but environmental
      conditions affecting attachment to and biofilm formation on abiotic surfaces have
      not been described. We did a study to determine the effects of temperature and
      nutrient availability on attachment and biofilm formation by E. sakazakii on
      stainless steel and enteral feeding tubes. Five strains grown to stationary phase
      in tryptic soy broth (TSB), infant formula broth (IFB), or lettuce juice broth
      (LJB) at 12 and 25 degrees C were examined for the extent to which they attach to
      these materials. Higher populations attached at 25 degrees C than at 12 degrees
      C. Stainless steel coupons and enteral feeding tubes were immersed for 24 h at 4
      degrees C in phosphate-buffered saline suspensions (7 log CFU/ml) to facilitate
      the attachment of 5.33 to 5.51 and 5.03 to 5.12 log CFU/cm(2), respectively,
      before they were immersed in TSB, IFB, or LJB, followed by incubation at 12 or 25
      degrees C for up to 10 days. Biofilms were not produced at 12 degrees C. The
      number of cells of test strains increased by 1.42 to 1.67 log CFU/cm(2) and 1.16
      to 1.31 log CFU/cm(2) in biofilms formed on stainless steel and feeding tubes,
      respectively, immersed in IFB at 25 degrees C; biofilms were not formed on TSB
      and LJB at 25 degrees C, indicating that nutrient availability plays a major role
      in processes leading to biofilm formation on the surfaces of these inert
      materials. These observations emphasize the importance of temperature control in
      reconstituted infant formula preparation and storage areas in preventing
      attachment and biofilm formation by E. sakazakii.

PMID- 16957204
TI  - Rapid, sensitive, and discriminating identification of Naegleria spp. by real
      time PCR and melting-curve analysis.
AB  - The free-living amoeboflagellate genus Naegleria includes one pathogenic and two
      potentially pathogenic species (Naegleria fowleri, Naegleria italica, and
      Naegleria australiensis) plus numerous benign organisms. Monitoring of bathing
      water, water supplies, and cooling systems for these pathogens requires a timely
      and reliable method for identification, but current DNA sequence-based methods
      identify only N. fowleri or require full sequencing to identify other species in
      the genus. A novel closed-tube method for distinguishing thermophilic Naegleria
      species is presented, using a single primer set and the DNA intercalating dye
      SYTO9 for real-time PCR and melting-curve analysis of the 5.8S ribosomal DNA gene
      and flanking noncoding spacers (ITS1, ITS2). Collection of DNA melting data at
      close temperature intervals produces highly informative melting curves with one
      or more recognizable melting peaks, readily distinguished for seven Naegleria
      species and the related Willaertia magna. Advantages over other methods used to
      identify these organisms include its comprehensiveness (encompassing all species
      tested to date), simplicity (no electrophoresis required to verify the product),
      and sensitivity (unambiguous identification from DNA equivalent to one cell).
      This approach should be applicable to a wide range of microorganisms of medical
      importance.

PMID- 16957205
TI  - Persistence of nontuberculous mycobacteria in a drinking water system after
      addition of filtration treatment.
AB  - There is evidence that drinking water may be a source of infections with
      pathogenic nontuberculous mycobacteria (NTM) in humans. One method by which NTM
      are believed to enter drinking water distribution systems is by their
      intracellular colonization of protozoa. Our goal was to determine whether we
      could detect a reduction in the prevalence of NTM recovered from an unfiltered
      surface drinking water system after the addition of ozonation and filtration
      treatment and to characterize NTM isolates by using molecular methods. We sampled
      water from two initially unfiltered surface drinking water treatment plants over
      a 29-month period. One plant received the addition of filtration and ozonation
      after 6 months of sampling. Sample sites included those at treatment plant
      effluents, distributed water, and cold water taps (point-of-use [POU] sites) in
      public or commercial buildings located within each distribution system. NTM were
      recovered from 27% of the sites. POU sites yielded the majority of NTM, with >50%
      recovery despite the addition of ozonation and filtration. Closely related
      electrophoretic groups of Mycobacterium avium were found to persist at POU sites
      for up to 26 months. Water collected from POU cold water outlets was persistently
      colonized with NTM despite the addition of ozonation and filtration to a drinking
      water system. This suggests that cold water POU outlets need to be considered as
      a potential source of chronic human exposure to NTM.

PMID- 16957206
TI  - Lettuce for human consumption collected in Costa Rica contains complex
      communities of culturable oxytetracycline- and gentamicin-resistant bacteria.
AB  - The present widespread use of antimicrobials in crop farming is based upon their
      successful application in human medicine. However, recent evidence suggests that
      the massive anthropogenic release of antimicrobials into the biosphere has
      selected for resistant bacteria and facilitated the transfer of resistance genes
      among them. This work deals with the examination of iceberg lettuce collected at
      10 farms from two regions in Costa Rica. Farmers from nine sampling sites
      regularly apply commercial formulations containing gentamicin, oxytetracycline,
      streptomycin, or a combination of them without being able to indicate how often
      and how much of these products have been sprayed onto the crops. One organic farm
      was also investigated for comparative purposes. Oxytetracycline- and gentamicin
      resistant bacteria were abundantly detected using selective enrichment cultures.
      Furthermore, colony mixtures from selective plates were characterized by
      chemotaxonomical and molecular fingerprinting methods. Both types of resistant
      communities accounted for a significant fraction of all culturable bacteria and
      included several resistance genes as well as factors for their potential
      horizontal transfer. Given the fact that lettuce is eaten raw, it may contribute
      to the dissemination of antimicrobial-resistant bacteria and/or their resistance
      genes from the environment to the microbial biota of the human intestine.

PMID- 16957207
TI  - Discrimination of multiple Dehalococcoides strains in a trichloroethene
      enrichment by quantification of their reductive dehalogenase genes.
AB  - While many anaerobic microbial communities are capable of reductively
      dechlorinating tetrachloroethene (PCE) and trichloroethene (TCE) to
      dichloroethene (DCE), vinyl chloride (VC), and finally ethene, the accumulation
      of the highly toxic intermediates, cis-DCE (cDCE) and VC, presents a challenge
      for bioremediation processes. Members of the genus Dehalococcoides are apparently
      solely responsible for dechlorination beyond DCE, but isolates of Dehalococcoides
      each metabolize only a subset of PCE dechlorination intermediates and the
      interactions among distinct Dehalococcoides strains that result in complete
      dechlorination are not well understood. Here we apply quantitative PCR to 16S
      rRNA and reductase gene sequences to discriminate and track Dehalococcoides
      strains in a TCE enrichment derived from soil taken from the Alameda Naval Air
      Station (ANAS) using a four-gene plasmid standard. This standard increased
      experimental accuracy such that 16S rRNA and summed reductase gene copy numbers
      matched to within 10%. The ANAS culture was found to contain only a single
      Dehalococcoides 16S rRNA gene sequence, matching that of D. ethenogenes 195, but
      both the vcrA and tceA reductive dehalogenase genes. Quantities of these two
      genes in the enrichment summed to the quantity of the Dehalococcoides 16S rRNA
      gene. Further, between ANAS subcultures enriched on TCE, cDCE, or VC, the
      relative copy number of the two dehalogenases shifted 14-fold, indicating that
      the genes are present in two different Dehalococcoides strains. Comparison of
      cell yields in VC-, cDCE-, and TCE-enriched subcultures suggests that the tceA
      containing strain is responsible for nearly all of the TCE and cDCE metabolism in
      ANAS, whereas the vcrA-containing strain is responsible for all of the VC
      metabolism.

PMID- 16957208
TI  - Quantification of the effects of salt stress and physiological state on
      thermotolerance of Bacillus cereus ATCC 10987 and ATCC 14579.
AB  - The food-borne pathogen Bacillus cereus can acquire enhanced thermal resistance
      through multiple mechanisms. Two Bacillus cereus strains, ATCC 10987 and ATCC
      14579, were used to quantify the effects of salt stress and physiological state
      on thermotolerance. Cultures were exposed to increasing concentrations of sodium
      chloride for 30 min, after which their thermotolerance was assessed at 50 degrees
      C. Linear and nonlinear microbial survival models, which cover a wide range of
      known inactivation curvatures for vegetative cells, were fitted to the
      inactivation data and evaluated. Based on statistical indices and model
      characteristics, biphasic models with a shoulder were selected and used for
      quantification. Each model parameter reflected a survival characteristic, and
      both models were flexible, allowing a reduction of parameters when certain
      phenomena were not present. Both strains showed enhanced thermotolerance after
      preexposure to (non)lethal salt stress conditions in the exponential phase. The
      maximum adaptive stress response due to salt preexposure demonstrated for
      exponential-phase cells was comparable to the effect of physiological state on
      thermotolerance in both strains. However, the adaptive salt stress response was
      less pronounced for transition- and stationary-phase cells. The distinct tailing
      of strain ATCC 10987 was attributed to the presence of a subpopulation of spores.
      The existence of a stable heat-resistant subpopulation of vegetative cells could
      not be demonstrated for either of the strains. Quantification of the adaptive
      stress response might be instrumental in understanding adaptation mechanisms and
      will allow the food industry to develop more accurate and reliable stress
      integrated predictive modeling to optimize minimal processing conditions.

PMID- 16957209
TI  - Identification, typing, and insecticidal activity of Xenorhabdus isolates from
      entomopathogenic nematodes in United Kingdom soil and characterization of the xpt
      toxin loci.
AB  - Xenorhabdus strains from entomopathogenic nematodes isolated from United Kingdom
      soils by using the insect bait entrapment method were characterized by partial
      sequencing of the 16S rRNA gene, four housekeeping genes (asd, ompR, recA, and
      serC) and the flagellin gene (fliC). Most strains (191/197) were found to have
      genes with greatest similarity to those of Xenorhabdus bovienii, and the
      remaining six strains had genes most similar to those of Xenorhabdus nematophila.
      Generally, 16S rRNA sequences and the sequence types based on housekeeping genes
      were in agreement, with a few notable exceptions. Statistical analysis implied
      that recombination had occurred at the serC locus and that moderate amounts of
      interallele recombination had also taken place. Surprisingly, the fliC locus
      contained a highly variable central region, even though insects lack an adaptive
      immune response, which is thought to drive flagellar variation in pathogens of
      higher organisms. All the X. nematophila strains exhibited a consistent pattern
      of insecticidal activity, and all contained the insecticidal toxin genes
      xptA1A2B1C1, which were present on a pathogenicity island (PAI). The PAIs were
      similar among the X. nematophila strains, except for partial deletions of a
      peptide synthetase gene and the presence of insertion sequences. Comparison of
      the PAI locus with that of X. bovienii suggested that the PAI integrated into the
      genome first and then acquired the xpt genes. The independent mobility of xpt
      genes was further supported by the presence of xpt genes in X. bovienii strain
      I73 on a type 2 transposon structure and by the variable patterns of insecticidal
      activity in X. bovienii isolates, even among closely related strains.

PMID- 16957210
TI  - Contraselectable streptomycin susceptibility determinant for genetic manipulation
      and analysis of Helicobacter pylori.
AB  - Many Helicobacter pylori genetic studies would benefit from an ability to move
      DNA sequences easily between strains by transformation and homologous
      recombination, without needing to leave a conventional drug resistance
      determinant at the targeted locus. Presented here is a two-gene cassette that can
      be selected both (i) against, due to a Campylobacter jejuni rpsL gene (dominant
      streptomycin susceptibility in cells also carrying an rpsL-str(r) allele), and
      (ii) for, due to an erm gene (erythromycin resistance). This rpsL,erm cassette's
      utility was assessed by using it to replace four gene loci (mdaB, frxA, fur, and
      nikR) in four streptomycin-resistant [Str(r)] strain backgrounds (derivatives of
      26695, SS1, X47, and G27MA). The resultant 16 strains (phenotypically
      erythromycin resistant [Erm(r)] and Str(s)) were each transformed with wild-type
      genomic DNAs, and Str(r) derivatives were selected. The desired Erm(s) Str(r)
      isolates were obtained at frequencies that ranged from 17 to 96% among Str(r)
      transformants, with the Erm(s) yield apparently depending on the strain
      background and genome location of the targeted locus. The ease of isolating
      unmarked transformants described here should be valuable for many H. pylori
      molecular genetic and evolutionary analyses.

PMID- 16957211
TI  - Integrated analysis of established and novel microbial and chemical methods for
      microbial source tracking.
AB  - Several microbes and chemicals have been considered as potential tracers to
      identify fecal sources in the environment. However, to date, no one approach has
      been shown to accurately identify the origins of fecal pollution in aquatic
      environments. In this multilaboratory study, different microbial and chemical
      indicators were analyzed in order to distinguish human fecal sources from
      nonhuman fecal sources using wastewaters and slurries from diverse geographical
      areas within Europe. Twenty-six parameters, which were later combined to form
      derived variables for statistical analyses, were obtained by performing methods
      that were achievable in all the participant laboratories: enumeration of fecal
      coliform bacteria, enterococci, clostridia, somatic coliphages, F-specific RNA
      phages, bacteriophages infecting Bacteroides fragilis RYC2056 and Bacteroides
      thetaiotaomicron GA17, and total and sorbitol-fermenting bifidobacteria;
      genotyping of F-specific RNA phages; biochemical phenotyping of fecal coliform
      bacteria and enterococci using miniaturized tests; specific detection of
      Bifidobacterium adolescentis and Bifidobacterium dentium; and measurement of four
      fecal sterols. A number of potentially useful source indicators were detected
      (bacteriophages infecting B. thetaiotaomicron, certain genotypes of F-specific
      bacteriophages, sorbitol-fermenting bifidobacteria, 24-ethylcoprostanol, and
      epycoprostanol), although no one source identifier alone provided 100% correct
      classification of the fecal source. Subsequently, 38 variables (both single and
      derived) were defined from the measured microbial and chemical parameters in
      order to find the best subset of variables to develop predictive models using the
      lowest possible number of measured parameters. To this end, several statistical
      or machine learning methods were evaluated and provided two successful predictive
      models based on just two variables, giving 100% correct classification: the ratio
      of the densities of somatic coliphages and phages infecting Bacteroides
      thetaiotaomicron to the density of somatic coliphages and the ratio of the
      densities of fecal coliform bacteria and phages infecting Bacteroides
      thetaiotaomicron to the density of fecal coliform bacteria. Other models with
      high rates of correct classification were developed, but in these cases, higher
      numbers of variables were required.

PMID- 16957212
TI  - Comparison of four different culture media for isolation and growth of type II
      and type I/III Mycobacterium avium subsp. paratuberculosis strains isolated from
      cattle and goats.
AB  - Culture is considered the definitive technique for Johne's disease diagnosis, and
      it is essential for later applications of certain molecular typing techniques. In
      this study, we have tested four solid media (Herrold's egg yolk medium [HEYM]
      with sodium pyruvate and mycobactin [HEYMm-SP], HEYM with mycobactin and without
      sodium pyruvate [HEYMm], Middlebrook 7H11 with mycobactin [Mm], and Lowenstein
      Jensen with mycobactin [LJm]) for isolation of Mycobacterium avium subsp.
      paratuberculosis strains in 319 tissue samples from cattle herds and goat flocks.
      We have shown that each of the two main groups of M. avium subsp.
      paratuberculosis (type II and type I/III) has different requirements for growth
      in the culture media studied. The recommended solid media for isolation of type
      I/III strains are LJm and Mm, since the combination of both media allowed the
      recovery of all these strains. The most widespread culture medium, HEYM, is not
      suitable for the isolation of this group of M. avium subsp. paratuberculosis
      strains. Regarding the type II strains, HEYMm-SP was the medium where more
      strains were isolated, but the other three media are also needed in order to
      recover all type II strains. The incubation period is also related to the strain
      type. In conclusion, because the type of strain cannot be known in advance of
      culture, coupled with the fact that cattle and goats can be infected with both
      groups of strains, we recommend the use of the four solid media and the
      prolongation of the incubation period to more than 6 months to detect
      paratuberculous herds/flocks and to determine the true prevalence of the
      infection.

PMID- 16957213
TI  - Microbially mediated biodegradation of hexahydro-1,3,5-trinitro-1,3,5- triazine
      by extracellular electron shuttling compounds.
AB  - The potential for humic substances to stimulate the reduction of hexahydro-1,3,5
      trinitro-1,3,5-triazine (RDX) was investigated. This study describes a novel
      approach for the remediation of RDX-contaminated environments using microbially
      mediated electron shuttling. Incubations without cells demonstrated that reduced
      AQDS transfers electrons directly to RDX, which was reduced without significant
      accumulation of the nitroso intermediates. Three times as much reduced AQDS
      (molar basis) was needed to completely reduce RDX. The rate and extent of RDX
      reduction differed greatly among electron shuttle/acceptor amendments for resting
      cell suspensions of Geobacter metallireducens and G. sulfurreducens with acetate
      as the sole electron donor. AQDS and purified humic substances stimulated the
      fastest rate of RDX reduction. The nitroso metabolites did not significantly
      accumulate in the presence of AQDS or humic substances. RDX reduction in the
      presence of poorly crystalline Fe(III) was relatively slow and metabolites
      transiently accumulated. However, adding humic substances or AQDS to Fe(III)
      containing incubations increased the reduction rates. Cells of G. metallireducens
      alone reduced RDX; however, the rate of RDX reduction was slow relative to AQDS
      amended incubations. These data suggest that extracellular electron shuttle
      mediated RDX transformation is not organism specific but rather is catalyzed by
      multiple Fe(III)- and humic-reducing species. Electron shuttle-mediated RDX
      reduction may eventually become a rapid and effective cleanup strategy in both
      Fe(III)-rich and Fe(III)-poor environments.

PMID- 16957214
TI  - Detection of Cryptosporidium oocysts in water: effect of the number of samples
      and analytic replicates on test results.
AB  - Due to the small number of Cryptosporidium oocysts in water, the number of
      samples taken and the analyses performed can affect the results of detection. In
      this study, 42 water samples were collected from one watershed during 20 storm
      events over 1 year, including duplicate or quadruplicate samples from 16 storm
      events. Ten samples from four events had three to eight subsamples. They were
      processed by EPA method 1623, and Cryptosporidium oocysts present were detected
      by immunofluorescent microscopy or PCR. Altogether, 24 of 39 samples (47 of 67
      samples and subsamples) analyzed by microscopy were positive for Cryptosporidium.
      In contrast, 36 of 42 samples (62 of 76 samples and subsamples) were positive by
      PCR, including 10 microscopy-negative samples (13 microscopy-negative samples and
      subsamples). Six of the 24 microscopy-positive samples were negative by PCR, and
      all samples had one or less oocyst in a 0.5-ml packed pellet volume calculated.
      Discordant results were obtained by microscopy and PCR from six and three of the
      storm events, respectively, with multiple samples. Discordant microscopy or PCR
      results were also obtained among subsamples. Most of the 14 Cryptosporidium
      genotypes were found over a brief period. Cryptosporidium-positive samples had a
      mean of 1.9 genotypes per sample, with 39 of the 62 positive samples/subsamples
      having more than one genotype. Samples/subsamples with more than one genotype had
      an overall PCR-positive rate of 73%, compared to 34% for those with one genotype.
      The PCR amplification rate of samples was affected by the volume of DNA used in
      PCR.

PMID- 16957215
TI  - Application of the [3H]leucine incorporation technique for quantification of
      bacterial secondary production associated with decaying wetland plant litter.
AB  - The radiolabeled leucine incorporation technique for quantifying rates of
      bacterial production has increased in popularity since its original description
      for bacterioplankton communities. Prior studies addressing incorporation
      conditions (e.g., substrate saturation) for bacterial communities in other
      habitats, such as decaying plant litter, have reported a wide range of final
      leucine concentrations (400 nM to 50 microM) required to achieve saturation-level
      uptake. We assessed the application of the [(3)H]leucine incorporation procedure
      for measuring bacterial production on decaying wetland plant litter. Substrate
      saturation experiments (nine concentrations, 10 nM to 50 microM final leucine
      concentration) were conducted on three dates for microbial communities colonizing
      the submerged litter of three emergent plant species (Typha angustifolia,
      Schoenoplectus validus, and Phragmites australis). A modified [(3)H]leucine
      protocol was developed by coupling previously described incubation and alkaline
      extraction protocols with microdialysis (500 molecular weight cutoff membrane) of
      the final radiolabeled protein extract. The incorporation of [(3)H]leucine into
      protein exhibited a biphasic saturation curve, with lower apparent K(m) values
      ranging from 400 nM to 4.2 microM depending on the plant species studied. Upper
      apparent K(m) values ranged from 1.3 to 59 microM. These results suggest
      differential uptake by litter-associated microbial assemblages, with the lower
      apparent K(m) values possibly representing bacterial uptake and higher apparent
      K(m) values representing a combination of both bacterial and nonbacterial (e.g.,
      eukaryotic) uptake.

PMID- 16957216
TI  - Abundance of narG, nirS, nirK, and nosZ genes of denitrifying bacteria during
      primary successions of a glacier foreland.
AB  - Quantitative PCR of denitrification genes encoding the nitrate, nitrite, and
      nitrous oxide reductases was used to study denitrifiers across a glacier
      foreland. Environmental samples collected at different distances from a receding
      glacier contained amounts of 16S rRNA target molecules ranging from 4.9 x 10(5)
      to 8.9 x 10(5) copies per nanogram of DNA but smaller amounts of narG, nirK, and
      nosZ target molecules. Thus, numbers of narG, nirK, nirS, and nosZ copies per
      nanogram of DNA ranged from 2.1 x 10(3) to 2.6 x 10(4), 7.4 x 10(2) to 1.4 x
      10(3), 2.5 x 10(2) to 6.4 x 10(3), and 1.2 x 10(3) to 5.5 x 10(3), respectively.
      The densities of 16S rRNA genes per gram of soil increased with progressing soil
      development. The densities as well as relative abundances of different
      denitrification genes provide evidence that different denitrifier communities
      develop under primary succession: higher percentages of narG and nirS versus 16S
      rRNA genes were observed in the early stage of primary succession, while the
      percentages of nirK and nosZ genes showed no significant increase or decrease
      with soil age. Statistical analyses revealed that the amount of organic
      substances was the most important factor in the abundance of eubacteria as well
      as of nirK and nosZ communities, and copy numbers of these two genes were the
      most important drivers changing the denitrifying community along the
      chronosequence. This study yields an initial insight into the ecology of bacteria
      carrying genes for the denitrification pathway in a newly developing alpine
      environment.

PMID- 16957217
TI  - Microbial communities in the surface mucopolysaccharide layer and the black band
      microbial mat of black band-diseased Siderastrea siderea.
AB  - Microbial community profiles and species composition associated with two black
      band-diseased colonies of the coral Siderastrea siderea were studied by 16S rRNA
      targeted gene cloning, sequencing, and amplicon-length heterogeneity PCR (LH
      PCR). Bacterial communities associated with the surface mucopolysaccharide layer
      (SML) of apparently healthy tissues of the infected colonies, together with
      samples of the black band disease (BBD) infections, were analyzed using the same
      techniques for comparison. Gene sequences, ranging from 424 to 1,537 bp, were
      retrieved from all positive clones (n = 43 to 48) in each of the four clone
      libraries generated and used for comparative sequence analysis. In addition to LH
      PCR community profiling, all of the clone sequences were aligned with LH-PCR
      primer sequences, and the theoretical lengths of the amplicons were determined.
      Results revealed that the community profiles were significantly different between
      BBD and SML samples. The SML samples were dominated by gamma-proteobacteria (53
      to 64%), followed by beta-proteobacteria (18 to 21%) and alpha-proteobacteria (5
      to 11%). In contrast, both BBD clone libraries were dominated by alpha
      proteobacteria (58 to 87%), followed by verrucomicrobia (2 to 10%) and 0 to 6%
      each of delta-proteobacteria, bacteroidetes, firmicutes, and cyanobacteria.
      Alphaproteobacterial sequence types related to the bacteria associated with toxin
      producing dinoflagellates were observed in BBD clone libraries but were not found
      in the SML libraries. Similarly, sequences affiliated with the family
      Desulfobacteraceae and toxin-producing cyanobacteria, both believed to be
      involved in BBD pathogenesis, were found only in BBD libraries. These data
      provide evidence for an association of numerous toxin-producing heterotrophic
      microorganisms with BBD of corals.

PMID- 16957218
TI  - Survival of environmental mycobacteria in Acanthamoeba polyphaga.
AB  - Free-living amoebae in water are hosts to many bacterial species living in such
      an environment. Such an association enables bacteria to select virulence factors
      and survive in adverse conditions. Waterborne mycobacteria (WBM) are important
      sources of community- and hospital-acquired outbreaks of nontuberculosis
      mycobacterial infections. However, the interactions between WBM and free-living
      amoebae in water have been demonstrated for only few Mycobacterium spp. We
      investigated the ability of a number (n = 26) of Mycobacterium spp. to survive in
      the trophozoites and cysts of Acanthamoeba polyphaga. All the species tested
      entered the trophozoites of A. polyphaga and survived at this location over a
      period of 5 days. Moreover, all Mycobacterium spp. survived inside cysts for a
      period of 15 days. Intracellular Mycobacterium spp. within amoeba cysts survived
      when exposed to free chlorine (15 mg/liter) for 24 h. These data document the
      interactions between free-living amoebae and the majority of waterborne
      Mycobacterium spp. Further studies are required to examine the effects of various
      germicidal agents on the survival of WBM in an aquatic environment.

PMID- 16957219
TI  - Comparison of two fingerprinting techniques, terminal restriction fragment length
      polymorphism and automated ribosomal intergenic spacer analysis, for
      determination of bacterial diversity in aquatic environments.
AB  - We investigated bacterial diversity in different aquatic environments (including
      marine and lagoon sediments, coastal seawater, and groundwater), and we compared
      two fingerprinting techniques (terminal restriction fragment length polymorphism
      [T-RFLP] and automated ribosomal intergenic spacer analysis [ARISA]) which are
      currently utilized for estimating richness and community composition. Bacterial
      diversity ranged from 27 to 99 phylotypes (on average, 56) using the T-RFLP
      approach and from 62 to 101 genotypes (on average, 81) when the same samples were
      analyzed using ARISA. The total diversity encountered in all matrices analyzed
      was 144 phylotypes for T-RFLP and 200 genotypes for ARISA. Although the two
      techniques provided similar results in the analysis of community structure,
      bacterial richness and diversity estimates were significantly higher using ARISA.
      These findings suggest that ARISA is more effective than T-RFLP in detecting the
      presence of bacterial taxa accounting for <5% of total amplified product. ARISA
      enabled also distinction among aquatic bacterial isolates of Pseudomonas spp.
      which were indistinguishable using T-RFLP analysis. Overall, the results of this
      study show that ARISA is more accurate than T-RFLP analysis on the 16S rRNA gene
      for estimating the biodiversity of aquatic bacterial assemblages.

PMID- 16957220
TI  - Molecular monitoring of the fecal microbiota of healthy human subjects during
      administration of lactulose and Saccharomyces boulardii.
AB  - Diet is a major factor in maintaining a healthy human gastrointestinal tract, and
      this has triggered the development of functional foods containing a probiotic
      and/or prebiotic component intended to improve the host's health via modulation
      of the intestinal microbiota. In this study, a long-term placebo-controlled
      crossover feeding study in which each subject received several treatments was
      performed to monitor the effect of a prebiotic substrate (i.e., lactulose), a
      probiotic organism (i.e., Saccharomyces boulardii), and their synbiotic
      combination on the fecal microbiota of three groups of 10 healthy human subjects
      differing in prebiotic dose and/or intake of placebo versus synbiotic. For this
      purpose, denaturing gradient gel electrophoresis (DGGE) analysis of 16S rRNA gene
      amplicons was used to detect possible changes in the overall bacterial
      composition using the universal V(3) primer and to detect possible changes at the
      subpopulation level using group-specific primers targeting the Bacteroides
      fragilis subgroup, the genus Bifidobacterium, the Clostridium lituseburense group
      (cluster XI), and the Clostridium coccoides-Eubacterium rectale group (cluster
      XIVa). Although these populations remained fairly stable based on DGGE profiling,
      one pronounced change was observed in the universal fingerprint profiles after
      lactulose ingestion. Band position analysis and band sequencing revealed that a
      band appearing or intensifying following lactulose administration could be
      assigned to the species Bifidobacterium adolescentis. Subsequent analysis with
      real-time PCR (RT-PCR) indicated a statistically significant increase (P < 0.05)
      in total bifidobacteria in one of the three subject groups after lactulose
      administration, whereas a similar but nonsignificant trend was observed in the
      other two groups. Combined RT-PCR results from two subject groups indicated a
      borderline significant increase (P = 0.074) of B. adolescentis following
      lactulose intake. The probiotic yeast S. boulardii did not display any detectable
      universal changes in the DGGE profiles, nor did it influence the bifidobacterial
      levels. This study highlighted the capacity of an integrated approach consisting
      of DGGE analysis and RT-PCR to monitor and quantify pronounced changes in the
      fecal microbiota of healthy subjects upon functional food administration.

PMID- 16957221
TI  - Effects of chloromethanes on growth of and deletion of the pce gene cluster in
      dehalorespiring Desulfitobacterium hafniense strain Y51.
AB  - The dehalorespiring Desulfitobacterium hafniense strain Y51 efficiently
      dechlorinates tetrachloroethene (PCE) to cis-1,2-dichloroethene (cis-DCE) via
      trichloroethene by PceA reductive dehalogenase encoded by the pceA gene. In a
      previous study, we found that the significant growth inhibition of strain Y51
      occurred in the presence of commercial cis-DCE. In this study, it turned out that
      the growth inhibition was caused by chloroform (CF) contamination of cis-DCE.
      Interestingly, CF did not affect the growth of PCE-nondechlorinating SD (small
      deletion) and LD (large deletion) variants, where the former fails to transcribe
      the pceABC genes caused by a deletion of the promoter and the latter lost the
      entire pceABCT gene cluster. Therefore, PCE-nondechlorinating variants, mostly LD
      variant, became predominant, and dechlorination activity was significantly
      reduced in the presence of CF. Moreover, such a growth inhibitory effect was also
      observed in the presence of carbon tetrachloride at 1 microM, but not carbon
      dichloride even at 1 mM.

PMID- 16957222
TI  - Environmental influences on Vibrio populations in northern temperate and boreal
      coastal waters (Baltic and Skagerrak Seas).
AB  - Even if many Vibrio spp. are endemic to coastal waters, their distribution in
      northern temperate and boreal waters is poorly studied. To identify environmental
      factors regulating Vibrio populations in a salinity gradient along the Swedish
      coastline, we combined Vibrio-specific quantitative competitive PCR with
      denaturant gradient gel electrophoresis-based genotyping. The total Vibrio
      abundance ranged from 4 x 10(3) to 9.6 x 10(4) cells liter(-1), with the highest
      abundances in the more saline waters of the Skagerrak Sea. Several Vibrio
      populations were present throughout the salinity gradient, with abundances of
      single populations ranging from 5 x 10(2) to 7 x 10(4) cells liter(-1). Clear
      differences were observed along the salinity gradient, where three populations
      dominated the more saline waters of the Skagerrak Sea and two populations
      containing mainly representatives of V. anguillarum and V. aestuarianus genotypes
      were abundant in the brackish waters of the Baltic Sea. Our results suggest that
      this apparent niche separation within the genus Vibrio may also be influenced by
      alternate factors such as nutrient levels and high abundances of dinoflagellates.
      A V. cholerae/V. mimicus population was detected in more than 50% of the samples,
      with abundances exceeding 10(3) cells liter(-1), even in the cold (annual average
      water temperature of around 5 degrees C) and low-salinity (2 to 4 per thousand)
      samples from the Bothnian Bay (latitude, 65 degrees N). The unsuspected and
      widespread occurrence of this population in temperate and boreal coastal waters
      suggests that potential Vibrio pathogens may also be endemic to cold and brackish
      waters and hence may represent a previously overlooked health hazard.

PMID- 16957223
TI  - Lysine-oriented charges trigger the membrane binding and activity of nukacin ISK
      1.
AB  - The antibacterial activities and membrane binding of nukacin ISK-1 and its
      fragments and mutants were evaluated to delineate the determinants governing
      structure-function relationships. The tail region (nukacin(1-7)) and ring region
      (nukacin(7-27)) were shown to have no antibacterial activity and also had no
      synergistic effect on each other or even on nukacin ISK-1. Both a fragment with
      three lysines in the N terminus deleted (nukacin(4-27)) and a mutant with three
      lysines in the N terminus replaced with alanine (K1-3A nukacin ISK-1) imparted
      very low activity (32-fold lower than nukacin ISK-1) and also exhibited a similar
      antagonistic effect on nukacin ISK-1. Addition of two lysine residues at the N
      terminus (+2K nukacin ISK-1) provided no further increased antibacterial
      activity. Surface plasmon resonance sensorgrams and kinetic rate constants
      determined by a BIAcore biosensor revealed that nukacin ISK-1 has remarkably
      higher binding affinity to anionic model membrane than to zwitterionic model
      membrane. Similar trends of strong binding responses and kinetics were indicated
      by the high affinities of nukacin ISK-1 and +2K nukacin ISK-1, but there was no
      binding of tail region, ring region, nukacin(4-27), and K1-3A nukacin ISK-1 to
      the anionic model membrane. Our findings therefore suggest that the complete
      structure of nukacin ISK-1 is necessary for its full activity, in which the N
      terminus three lysine residues play a crucial role in electrostatic binding to
      the target membrane and therefore nukacin ISK-1's ability to exert its potent
      antibacterial activity.

PMID- 16957224
TI  - Halotolerant cyanobacterium Aphanothece halophytica contains a betaine
      transporter active at alkaline pH and high salinity.
AB  - Aphanothece halophytica is a halotolerant alkaliphilic cyanobacterium which can
      grow in media of up to 3.0 M NaCl and pH 11. This cyanobacterium can synthesize
      betaine from glycine by three-step methylation using S-adenosylmethionine as a
      methyl donor. To unveil the mechanism of betaine uptake and efflux in this
      alkaliphile, we isolated and characterized a betaine transporter. A gene encoding
      a protein (BetT(A. halophytica)) that belongs to the betaine-choline-carnitine
      transporter (BCCT) family was isolated. Although the predicted isoelectric pH of
      a typical BCCT family transporter, OpuD of Bacillus subtilis, is basic, 9.54,
      that of BetT(A. halophytica) is acidic, 4.58. BetT(A. halophytica) specifically
      catalyzed the transport of betaine. Choline, gamma-aminobutyric acid, betaine
      aldehyde, sarcosine, dimethylglycine, and amino acids such as proline did not
      compete for the uptake of betaine by BetT(A. halophytica). Sodium markedly
      enhanced betaine uptake rates, whereas potassium and other cations showed no
      effect, suggesting that BetT(A. halophytica) is a Na(+)-betaine symporter.
      Betaine uptake activities of BetT(A. halophytica) were high at alkaline pH
      values, with the optimum pH around 9.0. Freshwater Synechococcus cells
      overexpressing BetT(A. halophytica) showed NaCl-activated betaine uptake
      activities with enhanced salt tolerance, allowing growth in seawater supplemented
      with betaine. Kinetic properties of betaine uptake in Synechococcus cells
      overexpressing BetT(A. halophytica) were similar to those in A. halophytica
      cells. These findings indicate that A. halophytica contains a Na(+)-betaine
      symporter that contributes to the salt stress tolerance at alkaline pH. BetT(A.
      halophytica) is the first identified transporter for compatible solutes in
      cyanobacteria.

PMID- 16957225
TI  - Relevance of the endosymbiosis of Blochmannia floridanus and carpenter ants at
      different stages of the life cycle of the host.
AB  - Expression of several genes possibly involved in the symbiotic relationship
      between the obligate intracellular endosymbiont Blochmannia floridanus and its
      ant host Camponotus floridanus was investigated at different developmental stages
      of the host by real-time quantitative PCR. These included a set of genes related
      to nitrogen metabolism (ureC, ureF, glnA, and speB) as well as genes involved in
      the synthesis of the aromatic amino acid tyrosine (tyrA, aspC, and hisC). The
      overall transcriptional activity of Blochmannia was found to be quite low during
      early developmental stages and to increase steadily with host age. However, a
      concerted peak of gene expression related to nitrogen recycling could be detected
      around the entire process of pupation, while expression of biosynthesis pathways
      for aromatic amino acids was elevated only during a short phase in pupation.
      These data suggest an important role of certain metabolic functions for the
      symbiotic interactions of the bacteria and an individual host organism in early
      phases of development. General relevance of Blochmannia for its ant host was
      tested in fostering experiments with worker groups of Camponotus floridanus, and
      their success in raising pupae from first-instar larvae was used as a fitness
      measure. Groups treated with antibiotics had a significantly reduced success in
      raising the brood in comparison to untreated control groups, indicating that the
      symbiosis is relevant for the development of the entire colony.

PMID- 16957226
TI  - Novel intermediates of acenaphthylene degradation by Rhizobium sp. strain CU-A1:
      evidence for naphthalene-1,8-dicarboxylic acid metabolism.
AB  - The acenaphthylene-degrading bacterium Rhizobium sp. strain CU-A1 was isolated
      from petroleum-contaminated soil in Thailand. This strain was able to degrade 600
      mg/liter acenaphthylene completely within three days. To elucidate the pathway
      for degradation of acenaphthylene, strain CU-A1 was mutagenized by transposon Tn5
      in order to obtain mutant strains deficient in acenaphthylene degradation.
      Metabolites produced from Tn5-induced mutant strains B1, B5, and A53 were
      purified by thin-layer chromatography and silica gel column chromatography and
      characterized by mass spectrometry. The results suggested that this strain
      cleaved the fused five-membered ring of acenaphthylene to form naphthalene-1,8
      dicarboxylic acid via acenaphthenequinone. One carboxyl group of naphthalene-1,8
      dicarboxylic acid was removed to form 1-naphthoic acid which was transformed into
      salicylic acid before metabolization to gentisic acid. This work is the first
      report of complete acenaphthylene degradation by a bacterial strain.

PMID- 16957227
TI  - Rapid quantitative detection of Lactobacillus sakei in meat and fermented
      sausages by real-time PCR.
AB  - A quick and simple method for quantitative detection of Lactobacillus sakei in
      fermented sausages was successfully developed. It is based on Chelex-100-based
      DNA purification and real-time PCR enumeration using a TaqMan fluorescence probe.
      Primers and probes were designed in the L. sakei 16S-23S rRNA intergenic
      transcribed spacer region, and the assay was evaluated using L. sakei genomic DNA
      and an artificially inoculated sausage model. The detection limit of this
      technique was approximately 3 cells per reaction mixture using both purified DNA
      and the inoculated sausage model. The quantification limit was established at 30
      cells per reaction mixture in both models. The assay was then applied to
      enumerate L. sakei in real samples, and the results were compared to the MRS agar
      count method followed by confirmation of the percentage of L. sakei colonies. The
      results obtained by real-time PCR were not statistically significantly different
      than those obtained by plate count on MRS agar (P > 0.05), showing a satisfactory
      agreement between both methods. Therefore, the real-time PCR assay developed can
      be considered a promising rapid alternative method for the quantification of L.
      sakei and evaluation of the implantation of starter strains of L. sakei in
      fermented sausages.

PMID- 16957228
TI  - Optimization of analytical parameters for inferring relationships among
      Escherichia coli isolates from repetitive-element PCR by maximizing
      correspondence with multilocus sequence typing data.
AB  - Repetitive-element PCR (rep-PCR) is a method for genotyping bacteria based on the
      selective amplification of repetitive genetic elements dispersed throughout
      bacterial chromosomes. The method has great potential for large-scale
      epidemiological studies because of its speed and simplicity; however, objective
      guidelines for inferring relationships among bacterial isolates from rep-PCR data
      are lacking. We used multilocus sequence typing (MLST) as a "gold standard" to
      optimize the analytical parameters for inferring relationships among Escherichia
      coli isolates from rep-PCR data. We chose 12 isolates from a large database to
      represent a wide range of pairwise genetic distances, based on the initial
      evaluation of their rep-PCR fingerprints. We conducted MLST with these same
      isolates and systematically varied the analytical parameters to maximize the
      correspondence between the relationships inferred from rep-PCR and those inferred
      from MLST. Methods that compared the shapes of densitometric profiles ("curve
      based" methods) yielded consistently higher correspondence values between data
      types than did methods that calculated indices of similarity based on shared and
      different bands (maximum correspondences of 84.5% and 80.3%, respectively). Curve
      based methods were also markedly more robust in accommodating variations in user
      specified analytical parameter values than were "band-sharing coefficient"
      methods, and they enhanced the reproducibility of rep-PCR. Phylogenetic analyses
      of rep-PCR data yielded trees with high topological correspondence to trees based
      on MLST and high statistical support for major clades. These results indicate
      that rep-PCR yields accurate information for inferring relationships among E.
      coli isolates and that accuracy can be enhanced with the use of analytical
      methods that consider the shapes of densitometric profiles.

PMID- 16957229
TI  - Two 2[5H]-furanones as possible signaling molecules in Lactobacillus helveticus.
AB  - Two 2[5H]-furanones, in association with medium-chain fatty acids, were released
      in whey by Lactobacillus helveticus exposed to oxidative and heat stresses. This
      species plays an important role in cheese technology, particularly for Swiss-type
      cheeses and Grana cheese. Moreover, it significantly contributes to cheese
      ripening by means of an early autolysis and the release of enzymes during
      processing. Experimental evidence of the involvement of the two 2[5H]-furanones,
      detected by a gas chromatography-mass spectrometry/solid-phase microextraction
      technique, in the autolysis phenomenon has been obtained. Zymograms performed by
      using renaturing sodium dodecyl sulfate-polyacrylamide gels were used to detect
      the bioactivity of the supernatants containing the two furanones on fresh cells
      of the same strain. In addition to bands corresponding to known autolysins, new
      autolysins were detected concomitant with the exposure of Lactobacillus
      helveticus to the supernatants, which can be regarded as conditioned media (CM),
      and to a commercial furanone, 5-ethyl-3-hydroxy-4-methyl-2[5H]-furanone (HEMFi),
      having spectral data similar to those of the newly described 2[5H]-furanones.
      Morphological changes were observed when fresh cells were exposed to CM
      containing the two 2[5H]-furanones and HEMFi. The two furanones produced by
      Lactobacillus helveticus, which met a number of criteria to be included in cell
      cell signaling molecules, have a presumptive molecular mass lower than those of
      already known 3[2H]-furanones having an autolytic activity and being produced by
      gram-negative bacteria. Moreover, they present a different chemical structure
      with respect to the furanones already identified as products of Lactococcus
      lactis subsp. cremoris or to those identified in some cheeses with Lactobacillus
      helveticus as a starter culture.

PMID- 16957230
TI  - Characterization of (R)-2-hydroxyisocaproate dehydrogenase and a family III
      coenzyme A transferase involved in reduction of L-leucine to isocaproate by
      Clostridium difficile.
AB  - The strictly anaerobic pathogenic bacterium Clostridium difficile occurs in the
      human gut and is able to thrive from fermentation of leucine. Thereby the amino
      acid is both oxidized to isovalerate plus CO(2) and reduced to isocaproate. In
      the reductive branch of this pathway, the dehydration of (R)-2-hydroxyisocaproyl
      coenzyme A (CoA) to (E)-2-isocaprenoyl-CoA is probably catalyzed via radical
      intermediates. The dehydratase requires activation by an ATP-dependent one
      electron transfer (J. Kim, D. Darley, and W. Buckel, FEBS J. 272:550-561, 2005).
      Prior to the dehydration, a dehydrogenase and a CoA transferase are supposed to
      be involved in the formation of (R)-2-hydroxyisocaproyl-CoA. Deduced amino acid
      sequences of ldhA and hadA from the genome of C. difficile showed high identities
      to d-lactate dehydrogenase and family III CoA transferase, respectively. Both
      putative genes encoding the dehydrogenase and CoA transferase were cloned and
      overexpressed in Escherichia coli; the recombinant Strep tag II fusion proteins
      were purified to homogeneity and characterized. The substrate specificity of the
      monomeric LdhA (36.5 kDa) indicated that 2-oxoisocaproate (K(m) = 68 muM, k(cat)
      = 31 s(-1)) and NADH were the native substrates. For the reverse reaction, the
      enzyme accepted (R)- but not (S)-2-hydroxyisocaproate and therefore was named (R)
      2-hydroxyisocaproate dehydrogenase. HadA showed CoA transferase activity with (R)
      2-hydroxyisocaproyl-CoA as a donor and isocaproate or (E)-2-isocaprenoate as an
      acceptor. By site-directed mutagenesis, the conserved D171 was identified as an
      essential catalytic residue probably involved in the formation of a mixed
      anhydride with the acyl group of the thioester substrate. However, neither
      hydroxylamine nor sodium borohydride, both of which are inactivators of the CoA
      transferase, modified this residue. The dehydrogenase and the CoA transferase fit
      well into the proposed pathway of leucine reduction to isocaproate.

PMID- 16957231
TI  - An oxidoreductase is involved in cercosporin degradation by the bacterium
      Xanthomonas campestris pv. zinniae.
AB  - The polyketide toxin cercosporin plays a key role in pathogenesis by fungal
      species of the genus Cercospora. The bacterium Xanthomonas campestris pv. zinniae
      is able to rapidly degrade this toxin. Growth of X. campestris pv. zinniae
      strains in cercosporin-containing medium leads to the breakdown of cercosporin
      and to the formation of xanosporic acid, a nontoxic breakdown product. Five non
      cercosporin-degrading mutants of a strain that rapidly degrades cercosporin (XCZ
      3) were generated by ethyl methanesulfonate mutagenesis and were then transformed
      with a genomic library from the wild-type strain. All five mutants were
      complemented with the same genomic clone, which encoded a putative
      transcriptional regulator and an oxidoreductase. Simultaneous expression of these
      two genes was necessary to complement the mutant phenotype. Sequence analysis of
      the mutants showed that all five mutants had point mutations in the
      oxidoreductase gene and no mutations in the regulator. Quantitative reverse
      transcription-PCR (RT-PCR) showed that the expression of both of these genes in
      the wild-type strain is upregulated after exposure to cercosporin. Both the
      oxidoreductase and transcriptional regulator genes were transformed into three
      non-cercosporin-degrading bacteria to determine if they are sufficient for
      cercosporin degradation. Quantitative RT-PCR analysis confirmed that the
      oxidoreductase was expressed in all transconjugants. However, none of the
      transconjugants were able to degrade cercosporin, suggesting that additional
      factors are required for cercosporin degradation. Further study of cercosporin
      degradation in X. campestris pv. zinniae may allow for the engineering of
      Cercospora-resistant plants by using a suite of genes.

PMID- 16957232
TI  - Inhibition of fungal colonization by Pseudoalteromonas tunicata provides a
      competitive advantage during surface colonization.
AB  - The marine epiphytic bacterium Pseudoalteromonas tunicata produces a range of
      extracellular secondary metabolites that inhibit an array of common fouling
      organisms, including fungi. In this study, we test the hypothesis that the
      ability to inhibit fungi provides P. tunicata with an advantage during
      colonization of a surface. Studies on a transposon-generated antifungal-deficient
      mutant of P. tunicata, FM3, indicated that a long-chain fatty acid-coenzyme A
      ligase is involved in the production of a broad-range antifungal compound by P.
      tunicata. Flow cell experiments demonstrated that production of an antifungal
      compound provided P. tunicata with a competitive advantage against a marine yeast
      isolate during surface colonization. This compound enabled P. tunicata to disrupt
      an already established fungal biofilm by decreasing the number of yeast cells
      attached to the surface by 66% +/- 9%. For in vivo experiments, the wild-type and
      FM3 strains of P. tunicata were used to inoculate the surface of the green alga
      Ulva australis. Double-gradient denaturing gradient gel electrophoresis analysis
      revealed that after 48 h, the wild-type P. tunicata had outcompeted the surface
      associated fungal community, whereas the antifungal-deficient mutant had no
      effect on the fungal community. Our data suggest that P. tunicata is an effective
      competitor against fungal surface communities in the marine environment.

PMID- 16957233
TI  - Multicopy integration of heterologous genes, using the lactococcal group II
      intron targeted to bacterial insertion sequences.
AB  - Group II introns are mobile genetic elements that can be redirected to invade
      specific genes. Here we describe the use of the lactococcal group II intron,
      Ll.ltrB, to achieve multicopy delivery of heterologous genes into the genome of
      Lactococcus lactis IL1403-UCD without the need for selectable markers. Ll.ltrB
      was retargeted to invade three transposase genes, the tra gene found in IS904
      (tra904), tra981, and tra983, of which 9, 10, and 14 copies, respectively, were
      present in IL1403-UCD. Intron invasion of tra904, tra981, and tra983 allele
      groups occurred at high frequencies, and individual segregants possessed anywhere
      from one to nine copies of intron in the respective tra alleles. To achieve
      multicopy delivery of a heterologous gene, a green fluorescent protein (GFP)
      marker was cloned into the tra904-targeted Ll.ltrB, and the resultant intron
      (Ll.ltrB::GFP) was induced to invade the L. lactis tra904 alleles. Segregants
      possessing Ll.ltrB::GFP in three, four, five, six, seven, and eight copies in
      different tra904 alleles were obtained. In general, increasing the chromosomal
      copy number of Ll.ltrB::GFP resulted in strains expressing successively higher
      levels of GFP. However, strains possessing the same number of Ll.ltrB::GFP copies
      within different sets of tra904 alleles exhibited differential GFP expression,
      and segregants possessing seven or eight copies of Ll.ltrB::GFP grew poorly upon
      induction, suggesting that GFP expression from certain combinations of alleles
      was detrimental. The highest level of GFP expression was observed from a specific
      six-copy variant that produced GFP at a level analogous to that obtained with a
      multicopy plasmid. In addition, the high level of GFP expression was stable for
      over 120 generations. This work demonstrates that stable multicopy integration of
      heterologous genes can be readily achieved in bacterial genomes with group II
      intron delivery by targeting repeated elements.

PMID- 16957234
TI  - Assay of poly(3-hydroxybutyrate) depolymerase activity and product determination.
AB  - Two methods for accurate poly(3-hydroxybutyrate) (PHB) depolymerase activity
      determination and quantitative and qualitative hydrolysis product determination
      are described. The first method is based on online determination of NaOH
      consumption rates necessary to neutralize 3-hydroxybutyric acid (3HB) and/or 3HB
      oligomers produced during the hydrolysis reaction and requires a pH-stat
      apparatus equipped with a software-controlled microliter pump for rapid and
      accurate titration. The method is universally suitable for hydrolysis of any type
      of polyhydroxyalkanoate or other molecules with hydrolyzable ester bonds, allows
      the determination of hydrolysis rates of as low as 1 nmol/min, and has a dynamic
      capacity of at least 6 orders of magnitude. By applying this method, specific
      hydrolysis rates of native PHB granules isolated from Ralstonia eutropha H16 were
      determined for the first time. The second method was developed for hydrolysis
      product identification and is based on the derivatization of 3HB oligomers into
      bromophenacyl derivates and separation by high-performance liquid chromatography.
      The method allows the separation and quantification of 3HB and 3HB oligomers up
      to the octamer. The two methods were applied to investigate the hydrolysis of
      different types of PHB by selected PHB depolymerases.

PMID- 16957235
TI  - Detection of microcystin-producing cyanobacteria in Finnish lakes with genus
      specific microcystin synthetase gene E (mcyE) PCR and associations with
      environmental factors.
AB  - We studied the frequency and composition of potential microcystin (MC) producers
      in 70 Finnish lakes with general and genus-specific microcystin synthetase gene E
      (mcyE) PCR. Potential MC-producing Microcystis, Planktothrixand Anabaena spp.
      existed in 70%, 63%, and 37% of the lake samples, respectively. Approximately two
      thirds of the lake samples contained one or two potential MC producers, while all
      three genera existed in 24% of the samples. In oligotrophic lakes, the occurrence
      of only one MC producer was most common. The combination of Microcystis and
      Planktothrix was slightly more prevalent than others in mesotrophic lakes, and
      the cooccurrence of all three MC producers was most widespread in both eutrophic
      and hypertrophic lakes. The proportion of the three-producer lakes increased with
      the trophic status of the lakes. In correlation analysis, the presence of
      multiple MC-producing genera was associated with higher cyanobacterial and
      phytoplankton biomass, pH, chlorophyll a, total nitrogen, and MC concentrations.
      Total nitrogen, pH, and the surface area of the lake predicted the occurrence
      probability of mcyE genes, whereas total phosphorus alone accounted for MC
      concentrations in the samples by logistic and linear regression analyses. In
      conclusion, the results suggested that eutrophication increased the cooccurrence
      of potentially MC-producing cyanobacterial genera, raising the risk of toxic
      bloom formation.

PMID- 16957236
TI  - Visible-light-induced bactericidal activity of a nitrogen-doped titanium
      photocatalyst against human pathogens.
AB  - The antibacterial activity of photocatalytic titanium dioxide (TiO(2)) substrates
      is induced primarily by UV light irradiation. Recently, nitrogen- and carbon
      doped TiO(2) substrates were shown to exhibit photocatalytic activities under
      visible-light illumination. Their antibacterial activity, however, remains to be
      quantified. In this study, we demonstrated that nitrogen-doped TiO(2) substrates
      have superior visible-light-induced bactericidal activity against Escherichia
      coli compared to pure TiO(2) and carbon-doped TiO(2) substrates. We also found
      that protein- and light-absorbing contaminants partially reduce the bactericidal
      activity of nitrogen-doped TiO(2) substrates due to their light-shielding
      effects. In the pathogen-killing experiment, a significantly higher proportion of
      all tested pathogens, including Shigella flexneri, Listeria monocytogenes, Vibrio
      parahaemolyticus, Staphylococcus aureus, Streptococcus pyogenes, and
      Acinetobacter baumannii, were killed by visible-light-illuminated nitrogen-doped
      TiO(2) substrates than by pure TiO(2) substrates. These findings suggest that
      nitrogen-doped TiO(2) has potential application in the development of alternative
      disinfectants for environmental and medical usages.

PMID- 16957237
TI  - Biotyping of enterotoxigenic Staphylococcus aureus by enterotoxin gene cluster
      (egc) polymorphism and spa typing analyses.
AB  - Thirty-five Staphylococcus aureus strains, including 10 reference strains and 25
      strains recovered from clinical specimens and food samples, were analyzed by PCR
      REA (restriction endonucleases analysis) of the egc operon and spa typing.
      Nineteen spa types and seven different egc operons, including four putative new
      egc variants, were revealed. In 13 strains, allelic variants of sei and/or seg
      were found. By an analysis of their nucleotide sequence identities, a new
      homogeneous cluster of a sei variant, called the sei variant, was detected in six
      strains. In addition, the prototype sei was shown to be more polymorphic than
      assumed so far. Seven strains possessed the recently described seg variant, also
      exhibiting several nucleotide exchanges. spa typing was more effective than REA
      egc grouping as a typing technique. Since, in some cases, the REA typing method
      was able to discriminate strains showing the same spa type, it must be considered
      for PCR approaches involved in diagnostic procedures and may be useful for
      epidemiological studies. Hence, the polyphasic approach used in this study can be
      reliably and advantageously applied for typing egc-positive S. aureus strains.

PMID- 16957238
TI  - Evaluation of freeze-dried kefir coculture as starter in feta-type cheese
      production.
AB  - The use of freeze-dried kefir coculture as a starter in the production of feta
      type cheese was investigated. Maturation of the produced cheese at 4 degrees C
      was monitored for up to 70 days, and the effects of the starter culture, the
      salting method, and the ripening process on quality characteristics were studied.
      The use of kefir coculture as a starter led to increased lactic acid
      concentrations and decreased pH values in the final product associated with
      significantly higher conversion rates compared to salted rennet cheese.
      Determination of bacterial diversity at the end of the ripening process in salted
      kefir and rennet cheeses by denaturing gradient gel electrophoresis technology,
      based on both DNA and RNA analyses, suggested a potential species-specific
      inhibition of members of the genera Staphylococcus and Psychrobacter by kefir
      coculture. The main active microbial associations in salted kefir cheese appeared
      to be members of the genera Pseudomonas and Lactococcus, while in salted rennet
      cheese, Oxalobacteraceae, Janthinobacterium, Psychrobacter, and Pseudomonas
      species were noted. The effect of the starter culture on the production of aroma
      related compounds responsible for cheese flavor was also studied by the solid
      phase microextraction-gas chromatography-mass spectrometry technique. Kefir
      coculture also appeared to extend the shelf life of unsalted cheese. Spoilage of
      kefir cheese was observed on the 9th and 20th days of preservation at 10 and 5
      degrees C, respectively, while spoilage in the corresponding rennet cheese was
      detected on the 7th and 16th days. Microbial counts during preservation of both
      types of unsalted cheese increased steadily and reached similar levels, with the
      exception of staphylococci, which were significantly lower in unsalted kefir
      cheese. All types of cheese produced with kefir as a starter were approved and
      accepted by the panel during the preliminary sensory evaluation compared to
      commercial feta-type cheese.

PMID- 16957240
TI  - Comparison of Salmonella enterica serovar Typhimurium LT2 and non-LT2 salmonella
      genomic sequences, and genotyping of salmonellae by using PCR.
AB  - Genes of Salmonella enterica serovar Typhimurium LT2 expected to be specifically
      present in Salmonella were selected using the Basic Local Alignment Search Tool
      (BLAST) program. The 152 selected genes were compared with 11 genomic sequences
      of Salmonella serovars, including Salmonella enterica subsp. I and IIIb and
      Salmonella bongori (V), and were clustered into 17 groups by their comparison
      patterns. A total of 38 primer pairs were constructed to represent each of the 17
      groups, and PCR was performed with various Salmonella subspecies including
      Salmonella enterica subsp. I, II, IIIa, IIIb, IV, VI, and V to evaluate a
      comprehensive DNA-based scheme for identification of Salmonella subspecies and
      the major disease-causing Salmonella serovars. Analysis of PCR results showed
      that Salmonella enterica subsp. I was critically divided from other subspecies,
      and Salmonella strains belonging to S. enterica subsp. I were clustered based on
      their serovars. In addition, genotypic relationships within S. enterica subsp. I
      by PCR results were investigated. Also, Salmonella signature genes, Salmonella
      enterica serovar Typhimurium signature genes, and Salmonella enterica subsp. I
      signature genes were demonstrated based on their PCR results. The described PCR
      method suggests a rapid and convenient method for identification of Salmonella
      serovars that can be used by nonspecialized laboratories. Genome sequence
      comparison can be a useful tool in epidemiologic and taxonomic studies of
      Salmonella.

PMID- 16957239
TI  - Genetic distinctions among clinical and environmental strains of Vibrio
      vulnificus.
AB  - Vibrio vulnificus causes rare but frequently fatal septicemia associated with raw
      oyster consumption by persons with underlying hepatic or immune system
      dysfunction. The virulence potential of environmental reservoirs appears widely
      distributed, because most strains are virulent in animal models; however, several
      investigations recently demonstrated genetic divergence among strains from
      clinical versus environmental origin at independent genetic loci. The present
      study used PCR to screen DNA polymorphisms in strains from environmental (n = 35)
      or clinical (n = 33) sources, and genomic relationships were determined by
      repetitive extragenic palindromic DNA PCR (rep-PCR) typing. Significant (P <
      0.01) association was observed for typical "clinical" or "environmental"
      polymorphism profiles based on strain origin. Most oyster isolates (88%),
      including all of those with the "environmental" profile, also formed a single rep
      PCR genogroup. Clinical isolates within this group did not have the typical
      "clinical" profile. On the other hand, clinical isolates with the typical
      polymorphism profile were distributed among multiple rep-PCR genogroups,
      demonstrating greater genetic diversity than was evident by profiling genetic
      polymorphisms. Wound isolates were genetically distinct from typical blood
      isolates by all assays. Strains from an outbreak of wound infections in Israel
      (biotype 3) were closely related to several U.S. strains by rep-PCR, indicating
      potential reservoirs of emerging disease. Strains genetically related to blood
      isolates appeared to be relatively rare in oysters, as only one had the
      "clinical" polymorphism profile or clustered by rep-PCR. However, this study was
      not an extensive survey, and more sampling using rep-PCR for sensitive genetic
      discrimination is needed to determine the virulence potential of environmental
      reservoirs.

PMID- 16957241
TI  - Associations between the ecology of virulent Rhodococcus equi and the
      epidemiology of R. equi pneumonia on Australian thoroughbred farms.
AB  - The ecology of virulent strains of Rhodococcus equi on horse farms is likely to
      influence the prevalence and severity of R. equi pneumonia in foals. This study
      examined the association between the ecology of virulent R. equi and the
      epidemiology of R. equi pneumonia by collecting air and soil samples over two
      breeding seasons (28 farm-year combinations) on Thoroughbred breeding farms with
      different reported prevalences of R. equi pneumonia. Colony blotting and DNA
      hybridization were used to detect and measure concentrations of virulent R. equi.
      The prevalence of R. equi pneumonia was associated with the airborne burden of
      virulent R. equi (both the concentration and the proportion of R. equi bacteria
      that were virulent) but was not associated with the burden of virulent R. equi in
      the soil. Univariable screening and multivariable model building were used to
      evaluate the effect of environmental and management factors on virulent R. equi
      burdens. Lower soil moisture concentrations and lower pasture heights were
      significantly associated with elevated airborne concentrations of virulent R.
      equi, as were the holding pens and lanes, which typically were sandy, dry, and
      devoid of pasture cover. Few variables appeared to influence concentrations of
      virulent R. equi in soil. Acidic soil conditions may have contributed to an
      elevated proportion of virulent strains within the R. equi population.
      Environmental management strategies that aim to reduce the level of exposure of
      susceptible foals to airborne virulent R. equi are most likely to reduce the
      impact of R. equi pneumonia on endemically affected farms.

PMID- 16957242
TI  - Reductive dehalogenase gene expression as a biomarker for physiological activity
      of Dehalococcoides spp.
AB  - This study characterizes the transcriptional expression of the reductive
      dehalogenase (RDase)-encoding tceA and vcrA genes and evaluates their
      applicability as potential biological markers of Dehalococcoides activity. When
      Dehalococcoides ethenogenes 195 was provided with trichloroethene (TCE) as the
      electron acceptor, the expression of the tceA gene increased by 90-fold relative
      to that in cells starved of chlorinated ethenes, demonstrating that tceA gene
      expression is indicative of the active physiological state of this strain. In a
      Dehalococcoides-containing enrichment culture that contains both the tceA and
      vcrA genes, the tceA gene was up-regulated in response to TCE and cis-1,2
      dichloroethene (cDCE) exposure, while the vcrA gene was up-regulated in response
      to TCE, cDCE, and vinyl chloride (VC). When chlorinated ethenes were depleted,
      the RDase-encoding gene transcripts decayed exponentially, with a half-life
      between 4.8 and 6.1 h, until they reached a stable background level after 2 days.
      We found that while gene expression correlated generally to the presence of
      chlorinated ethenes, there was no apparent direct relationship between RDase
      encoding transcript numbers and respective rates of TCE, cDCE, and VC
      dechlorination activities. However, elevated tceA and vcrA expression did
      correlate with chlorinated-ethene reduction beyond cDCE, suggesting that elevated
      RDase-encoding transcript numbers could serve as a biomarker for the
      physiological ability of Dehalococcoides spp. to dechlorinate beyond cDCE.

PMID- 16957243
TI  - Occurrence of 1-glyceryl-1-myo-inosityl phosphate in hyperthermophiles.
AB  - The accumulation of compatible solutes was studied in the hyperthermophilic
      bacterium Aquifex pyrophilus as a function of the temperature and the NaCl
      concentration of the growth medium. Nuclear magnetic resonance analysis of cell
      extracts revealed the presence of alpha- and beta-glutamate, di-mannosyl-di-myo
      inositol phosphate, di-myo-inositol phosphate, and an additional compound here
      identified as 1-glyceryl-1-myo-inosityl phosphate. All solutes accumulated by A.
      pyrophilus are negatively charged at physiological pH. The intracellular levels
      of di-myo-inositol phosphate increased in response to supraoptimal growth
      temperature, while alpha- and beta-glutamate accumulated in response to osmotic
      stress, especially at growth temperatures below the optimum. The newly discovered
      compound, 1-glyceryl-1-myo-inosityl phosphate, appears to play a double role in
      osmo- and thermoprotection, since its intracellular pool increased primarily in
      response to a combination of osmotic and heat stresses. This work also uncovered
      the nature of the unknown compound, previously detected in Archaeoglobus fulgidus
      (L. O. Martins et al., Appl. Environ. Microbiol. 63:896-902, 1997). The curious
      structural relationship between diglycerol phosphate (found only in Archaeoglobus
      species), di-myo-inositol phosphate (a canonical solute of hyperthermophiles),
      and the newly identified solute is highlighted. This is the first report on the
      occurrence of 1-glyceryl-1-myo-inosityl phosphate in living systems.

PMID- 16957244
TI  - Use of DNA quantification to measure growth and autolysis of Lactococcus and
      Propionibacterium spp. in mixed populations.
AB  - Autolysis is self-degradation of the bacterial cell wall that results in the
      release of enzymes and DNA. Autolysis of starter bacteria, such as lactococci and
      propionibacteria, is essential for cheese ripening, but our understanding of this
      important process is limited. This is mainly because the current tools for
      measuring autolysis cannot readily be used for analysis of bacteria in mixed
      populations. We have now addressed this problem by species-specific detection and
      quantification of free DNA released during autolysis. This was done by use of 16S
      rRNA gene single-nucleotide extension probes in combination with competitive PCR.
      We analyzed pure and mixed populations of Lactococcus lactis subsp. lactis and
      three different species of Propionibacterium. Results showed that L. lactis
      subsp. lactis INF L2 autolyzed first, followed by Propionibacterium
      acidipropionici ATCC 4965, Propionibacterium freudenreichii ISU P59, and then
      Propionibacterium jensenii INF P303. We also investigated the autolytic effect of
      rennet (commonly used in cheese production). We found that the effect was highly
      strain specific, with all the strains responding differently. Finally, autolysis
      of L. lactis subsp. lactis INF L2 and P. freudenreichii ISU P59 was analyzed in a
      liquid cheese model. Autolysis was detected later in this cheese model system
      than in broth media. A challenge with DNA, however, is DNA degradation. We
      addressed this challenge by using a DNA degradation marker. We obtained a good
      correlation between the degradation of the marker and the target in a model
      experiment. We conclude that our DNA approach will be a valuable tool for use in
      future analyses and for understanding autolysis in mixed bacterial populations.

PMID- 16957245
TI  - Transcriptomic assessment of isozymes in the biphenyl pathway of Rhodococcus sp.
      strain RHA1.
AB  - Rhodococcus sp. RHA1 grows on a broad range of aromatic compounds and vigorously
      degrades polychlorinated biphenyls (PCBs). Previous work identified RHA1 genes
      encoding multiple isozymes for most of the seven steps of the biphenyl (BPH)
      pathway, provided evidence for coexpression of some of these isozymes, and
      indicated the involvement of some of these enzymes in the degradation of BPH,
      ethylbenzene (ETB), and PCBs. To investigate the expression of these isozymes and
      better understand how they contribute to the robust degradative capacity of RHA1,
      we comprehensively analyzed the 9.7-Mb genome of RHA1 for BPH pathway genes and
      characterized the transcriptome of RHA1 growing on benzoate (BEN), BPH, and ETB.
      Sequence analyses revealed 54 potential BPH pathway genes, including 28 not
      previously reported. Transcriptomic analysis with a DNA microarray containing 70
      mer probes for 8,213 RHA1 genes revealed a suite of 320 genes of diverse
      functions that were upregulated during growth both on BPH and on ETB, relative to
      growth on the control substrate, pyruvate. By contrast, only 65 genes were
      upregulated during growth on BEN. Quantitative PCR assays confirmed microarray
      results for selected genes and indicated that some of the catabolic genes were
      upregulated over 10,000-fold. Our analysis suggests that up to 22 enzymes,
      including 8 newly identified ones, may function in the BPH pathway of RHA1. The
      relative expression levels of catabolic genes did not differ for BPH and ETB,
      suggesting a common regulatory mechanism. This study delineated a suite of
      catabolic enzymes for biphenyl and alkyl-benzenes in RHA1, which is larger than
      previously recognized and which may serve as a model for catabolism in other
      environmentally important bacteria having large genomes.

PMID- 16957246
TI  - Global transcriptional and physiological responses of Saccharomyces cerevisiae to
      ammonium, L-alanine, or L-glutamine limitation.
AB  - The yeast Saccharomyces cerevisiae encounters a range of nitrogen sources at
      various concentrations in its environment. The impact of these two parameters on
      transcription and metabolism was studied by growing S. cerevisiae in chemostat
      cultures with l-glutamine, l-alanine, or l-ammonium in limitation and by growing
      cells in an excess of ammonium. Cells grown in l-alanine-limited cultures had
      higher biomass yield per nitrogen mole (19%) than those from ammonium-limited
      cultures. Whole-genome transcript profiles were analyzed with a genome-scale
      metabolic model that suggested increased anabolic activity in l-alanine-limited
      cells. The changes in these cells were found to be focused around pyruvate,
      acetyl coenzyme A, glyoxylate, and alpha-ketoglutarate via increased levels of
      ALT1, DAL7, PYC1, GDH2, and ADH5 and decreased levels of GDH3, CIT2, and ACS1
      transcripts. The transcript profiles were then clustered. Approximately 1,400
      transcripts showed altered levels when amino acid-grown cells were compared to
      those from ammonium. Another 400 genes had low transcript levels when ammonium
      was in excess. Overrepresentation of the GATAAG element in their promoters
      suggests that nitrogen catabolite repression (NCR) may be responsible for this
      regulation. Ninety-one genes had transcript levels on both l-glutamine and
      ammonium that were decreased compared to those on l-alanine, independent of the
      concentration. The GATAAG element in these genes suggests two groups of NCR
      responsive genes, those that respond to high levels of nitrogen and those that
      respond to levels below 30 muM. In conclusion, our results reveal that the
      nitrogen source has substantial influence on the transcriptome of yeasts and that
      transcriptional changes may be correlated to physiology via a metabolic model.

PMID- 16957247
TI  - Composition and metabolic activities of bacterial biofilms colonizing food
      residues in the human gut.
AB  - Bacteria growing in the human large intestine live in intimate association with
      the host and play an important role in host digestive processes, gut physiology,
      and metabolism. Fecal bacteria have been investigated extensively, but few
      studies have been done on biofilms that form on digestive wastes in the large
      bowel. The aims of this investigation were to investigate the composition and
      metabolic activities of bacterial communities that colonize the surfaces of food
      residues in fecal material, with respect to their role in the fermentation of
      complex carbohydrates. Fresh stools were obtained from 15 healthy donors, and
      food residues were separated by filtration. Adherent bacteria were removed by
      surfactant treatment for microbiological analysis and fermentation studies.
      Scanning electron microscopy and fluorescent in situ hybridization in conjunction
      with confocal laser scanning microscopy (CLSM) were used to visualize intact
      biofilms. Results showed that bacterial populations strongly adhering to
      particulate matter were phenotypically similar in composition to unattached
      communities, with bacteroides and bifidobacteria predominating. Biofilms
      comprised a mixture of living and dead bacteria, and CLSM showed that
      bifidobacteria in the biofilms occurred as isolated dispersed cells and in
      microcolonies near the interface with the substratum. Fermentation experiments
      with a variety of complex carbohydrates demonstrated that biofilm populations
      were more efficient in digesting polysaccharides, while nonadhering communities
      fermented oligosaccharides most rapidly. Acetate was the principal fermentation
      product formed by biofilm bacteria, whereas higher levels of butyrate were
      produced by nonadherent populations, showing that the two communities were
      metabolically distinct.

PMID- 16957249
TI  - Characterization of phototrophic purple nonsulfur bacteria forming colored
      microbial mats in a swine wastewater ditch.
AB  - The community structure of pink-colored microbial mats naturally occurring in a
      swine wastewater ditch was studied by culture-independent biomarker and molecular
      methods as well as by conventional cultivation methods. The wastewater in the
      ditch contained acetate and propionate as the major carbon nutrients. Thin
      section electron microscopy revealed that the microbial mats were dominated by
      rod-shaped cells containing intracytoplasmic membranes of the lamellar type.
      Smaller numbers of oval cells with vesicular internal membranes were also found.
      Spectroscopic analyses of the cell extract from the biomats showed the presence
      of bacteriochlorophyll a and carotenoids of the spirilloxanthin series.
      Ubiquinone-10 was detected as the major quinone. A clone library of the
      photosynthetic gene, pufM, constructed from the bulk DNA of the biomats showed
      that all of the clones were derived from members of the genera Rhodobacter and
      Rhodopseudomonas. The dominant phototrophic bacteria from the microbial mats were
      isolated by cultivation methods and identified as being of the genera Rhodobacter
      and Rhodopseudomonas by studying 16S rRNA and pufM gene sequence information.
      Experiments of oxygen uptake with lower fatty acids revealed that the freshly
      collected microbial mats and the Rhodopseudomonas isolates had a wider spectrum
      of carbon utilization and a higher affinity for acetate than did the Rhodobacter
      isolates. These results demonstrate that the microbial mats were dominated by the
      purple nonsulfur bacteria of the genera Rhodobacter and Rhodopseudomonas, and the
      bioavailability of lower fatty acids in wastewater is a key factor allowing the
      formation of visible microbial mats with these phototrophs.

PMID- 16957248
TI  - Elucidation of the hrp clusters of Xanthomonas oryzae pv. oryzicola that control
      the hypersensitive response in nonhost tobacco and pathogenicity in susceptible
      host rice.
AB  - Xanthomonas oryzae pv. oryzicola, the cause of bacterial leaf streak in rice,
      possesses clusters of hrp genes that determine its ability to elicit a
      hypersensitive response (HR) in nonhost tobacco and pathogenicity in host rice. A
      27-kb region of the genome of X. oryzae pv. oryzicola (RS105) was identified and
      sequenced, revealing 10 hrp, 9 hrc (hrp conserved), and 8 hpa (hrp-associated)
      genes and 7 regulatory plant-inducible promoter boxes. While the region from hpa2
      to hpaB and the hrpF operon resembled the corresponding genes of other
      xanthomonads, the hpaB-hrpF region incorporated an hrpE3 gene that was not
      present in X. oryzae pv. oryzae. We found that an hrpF mutant had lost the
      ability to elicit the HR in tobacco and pathogenicity in adult rice plants but
      still caused water-soaking symptoms in rice seedlings and that Hpa1 is an HR
      elicitor in nonhost tobacco whose expression is controlled by an hrp regulator,
      HrpX. Using an Hrp phenotype complementation test, we identified a small hrp
      cluster containing the hrpG and hrpX regulatory genes, which is separated from
      the core hrp cluster. In addition, we identified a gene, prhA (plant-regulated
      hrp), that played a key role in the Hrp phenotype of X. oryzae pv. oryzicola but
      was neither in the core hrp cluster nor in the hrp regulatory cluster. A prhA
      mutant failed to reduce the HR in tobacco and pathogenicity in rice but caused
      water-soaking symptoms in rice. This is the first report that X. oryzae pv.
      oryzicola possesses three separate DNA regions for HR induction in nonhost
      tobacco and pathogenicity in host rice, which will provide a fundamental base to
      understand pathogenicity determinants of X. oryzae pv. oryzicola compared with
      those of X. oryzae pv. oryzae.

PMID- 16957250
TI  - Temporal changes in microscale colonization of the phylloplane by Aureobasidium
      pullulans.
AB  - Colonization of apple leaves by the yeastlike fungus Aureobasidium pullulans was
      followed quantitatively and spatially at a microscale level throughout two
      growing seasons. Ten field leaves were sampled on 11 dates in 2003 and 15 dates
      in 2004. Using an A. pullulans-specific fluorescence in situ hybridization probe
      and epifluorescence microscopy, we enumerated total cells, swollen-cells and
      chlamydospores (SCC), and blastospores/mm(2) on leaf features, including the
      midvein, other (smaller) veins, and the interveinal regions. By 7 July 2003 and 7
      June 2004, the total numbers of A. pullulans cells/mm(2) were significantly
      higher (P < 0.05) on the midvein and other veins than in the interveinal regions.
      This pattern remained consistent thereafter. The primary colonizing morphotype in
      all regions at all dates was the SCC form, although blastospores always occurred
      in low numbers. Occupancy was quantified based on the percentage of microscope
      fields of a particular leaf feature containing > or =1 A. pullulans cell. In
      general, as seasons progressed, the percent occupancy of features increased and,
      for most midvein and veinal features, approximated 100% at the end of both
      growing seasons. Except for early collections, when A. pullulans cell numbers
      were low, the percent occupancy of interveinal regions was lower than that of the
      midvein or other veinal regions. A. pullulans was distributed primarily as single
      cells throughout the seasons in interveinal regions. On the midvein and other
      veins, colonies of > or =4 cells developed over time, and more cells occurred in
      colonies than as singletons by August. Our results demonstrate that A. pullulans
      primarily colonizes veins, where populations appear to increase by growth in
      situ. This pattern is established early in the growing season and persists.

PMID- 16957251
TI  - Capture and retention of Cryptosporidium parvum oocysts by Pseudomonas aeruginosa
      biofilms.
AB  - The association of Cryptosporidium oocysts with biofilm communities can influence
      the propagation of this pathogen through both environmental systems and water
      treatment systems. We observed the capture and retention of C. parvum oocysts in
      Pseudomonas aeruginosa biofilms using laboratory flow cells. Biofilms were
      developed in two different growth media using two different strains of P.
      aeruginosa, a wild-type strain (PAO1) and a strain that overproduces the
      exopolysaccharide alginate (PDO300). Confocal laser-scanning microscopy was used
      in conjunction with image analysis to assess the structure of the biofilms prior
      to introducing oocysts into the flow cells. More oocysts were captured by the
      biofilm-coated surfaces than the abiotic glass surface in both media. There was
      no significant difference in capture across the two strains of P. aeruginosa
      biofilm, but the fraction of oocysts captured was positively related to biofilm
      roughness and surface-area-to-volume ratio. Once captured, oocysts were retained
      in the biofilm for more than 24 h and were not released after a 40-fold increase
      in the system flow rate. We believe the capture and retention of oocysts by
      biofilm communities can impact the environmental transmission of C. parvum, and
      this interaction should be taken into consideration when predicting the migration
      of pathogens in the environment.

PMID- 16957252
TI  - Quantitative determination of free-DNA uptake in river bacteria at the single
      cell level by in situ rolling-circle amplification.
AB  - Detection of plasmid DNA uptake in river bacteria at the single-cell level was
      carried out by rolling-circle amplification (RCA). Uptake of a plasmid containing
      the green fluorescent protein gene (gfp) by indigenous bacteria from two rivers
      in Osaka, Japan, was monitored for 506 h using this in situ gene amplification
      technique with optimized cell permeabilization conditions. Plasmid uptake
      determined by in situ RCA was compared to direct counts of cells expressing gfp
      under fluorescence microscopy to examine differences in detection sensitivities
      between the two methods. Detection of DNA uptake as monitored by in situ RCA was
      20 times higher at maximum than that by direct counting of gfp-expressing cells.
      In situ RCA could detect bacteria taking up the plasmid in several samples in
      which no gfp-expressing cells were apparent, indicating that in situ gene
      amplification techniques can be used to determine accurate rates of extracellular
      DNA uptake by indigenous bacteria in aquatic environments.

PMID- 16957253
TI  - Methane- and sulfur-metabolizing microbial communities dominate the Lost City
      hydrothermal field ecosystem.
AB  - Hydrothermal venting and the formation of carbonate chimneys in the Lost City
      hydrothermal field (LCHF) are driven predominantly by serpentinization reactions
      and cooling of mantle rocks, resulting in a highly reducing, high-pH environment
      with abundant dissolved hydrogen and methane. Phylogenetic and terminal
      restriction fragment length polymorphism analyses of 16S rRNA genes in fluids and
      carbonate material from this site indicate the presence of organisms similar to
      sulfur-oxidizing, sulfate-reducing, and methane-oxidizing Bacteria as well as
      methanogenic and anaerobic methane-oxidizing Archaea. The presence of these
      metabolic groups indicates that microbial cycling of sulfur and methane may be
      the dominant biogeochemical processes active within this ultramafic rock-hosted
      environment. 16S rRNA gene sequences grouping within the Methylobacter and
      Thiomicrospira clades were recovered from a chemically diverse suite of carbonate
      chimney and fluid samples. In contrast, 16S rRNA genes corresponding to the Lost
      City Methanosarcinales phylotype were found exclusively in high-temperature
      chimneys, while a phylotype of anaerobic methanotrophic Archaea (ANME-1) was
      restricted to lower-temperature, less vigorously venting sites. A
      hyperthermophilic habitat beneath the LCHF may be reflected by 16S rRNA gene
      sequences belonging to Thermococcales and uncultured Crenarchaeota identified in
      vent fluids. The finding of a diverse microbial ecosystem supported by the
      interaction of high-temperature, high-pH fluids resulting from serpentinization
      reactions in the subsurface provides insight into the biogeochemistry of what may
      be a pervasive process in ultramafic subseafloor environments.

PMID- 16957254
TI  - Increase in terminal restriction fragments of Bacteroidetes-derived 16S rRNA
      genes after administration of short-chain fructooligosaccharides.
AB  - It is well known that short chain fructooligosaccharides (scFOS) modify
      intestinal microbiota in animals as well as in humans. Since most murine
      intestinal bacteria are still uncultured, it is difficult for a culturing method
      to detect changes in intestinal microbiota after scFOS administration in a mouse
      model. In this study, we sought markers of positive change in murine intestinal
      microbiota after scFOS administration using terminal restriction fragment length
      polymorphism (T-RFLP) analysis, which is a culture-independent method. The T-RFLP
      profiles showed that six terminal restriction fragments (T-RFs) were
      significantly increased after scFOS administration. Phylogenetic analysis of the
      16S rRNA partial gene sequences of murine fecal bacteria suggested that four of
      six T-RFs that increased after scFOS administration were derived from the 16S
      rRNA genes of the class Bacteroidetes. Preliminary quantification of
      Bacteroidetes by real-time PCR suggests that the 16S rRNA genes derived from
      Bacteroidetes were increased by scFOS administration. Therefore, the T-RFs
      derived from Bacteroidetes are good markers of change of murine intestinal
      microbiota after scFOS administration.

PMID- 16957255
TI  - Assessment of genes associated with Streptococcus mutans biofilm morphology.
AB  - Streptococcus mutans, the major pathogen responsible for dental caries in humans,
      is a biofilm-forming bacterium. In the present study, 17 different pulsed-field
      gel electrophoresis patterns of genomic DNA were identified in S. mutans
      organisms isolated clinically from whole saliva. The S. mutans isolates showed
      different abilities to form biofilms on polystyrene surfaces in semidefined
      minimal medium cultures. Following cultivation in a flow cell system in tryptic
      soy broth with 0.25% sucrose and staining using a BacLight LIVE/DEAD system, two
      strains, designated FSC-3 and FSC-4, showed the greatest and least, respectively,
      levels of biofilm formation when examined with confocal laser scanning
      microscopy. Further, image analyses of spatial distribution and architecture were
      performed to quantify the merged green (live cells) and red (dead cells) light.
      The light intensity of the FSC-3 biofilm was greater than that of the FSC-4
      biofilm in the bottom area but not in the top area. S. mutans whole-genome array
      results showed that approximately 3.8% of the genes were differentially expressed
      in the two strains, of which approximately 2.2%, including bacitracin transport
      ATP-binding protein gene glrA and a BLpL-like putative immunity protein gene,
      were activated in FSC-3. In addition, about 1.6% of the genes, including those
      associated with phosphotransferase system genes, were repressed. Analyses of the
      glrA-deficient strains and reverse transcription-PCR confirmed the role of the
      gene in biofilm formation. Differential assessment of biofilm-associated genes in
      clinical strains may provide useful information for understanding the
      morphological development of streptococcal biofilm, as well as for colonization
      of S. mutans.

PMID- 16957257
TI  - Complete genome sequence of the marine, chemolithoautotrophic, ammonia-oxidizing
      bacterium Nitrosococcus oceani ATCC 19707.
AB  - The gammaproteobacterium Nitrosococcus oceani (ATCC 19707) is a gram-negative
      obligate chemolithoautotroph capable of extracting energy and reducing power from
      the oxidation of ammonia to nitrite. Sequencing and annotation of the genome
      revealed a single circular chromosome (3,481,691 bp; G+C content of 50.4%) and a
      plasmid (40,420 bp) that contain 3,052 and 41 candidate protein-encoding genes,
      respectively. The genes encoding proteins necessary for the function of known
      modes of lithotrophy and autotrophy were identified. Contrary to
      betaproteobacterial nitrifier genomes, the N. oceani genome contained two
      complete rrn operons. In contrast, only one copy of the genes needed to
      synthesize functional ammonia monooxygenase and hydroxylamine oxidoreductase, as
      well as the proteins that relay the extracted electrons to a terminal electron
      acceptor, were identified. The N. oceani genome contained genes for 13 complete
      two-component systems. The genome also contained all the genes needed to
      reconstruct complete central pathways, the tricarboxylic acid cycle, and the
      Embden-Meyerhof-Parnass and pentose phosphate pathways. The N. oceani genome
      contains the genes required to store and utilize energy from glycogen inclusion
      bodies and sucrose. Polyphosphate and pyrophosphate appear to be integrated in
      this bacterium's energy metabolism, stress tolerance, and ability to assimilate
      carbon via gluconeogenesis. One set of genes for type I ribulose-1,5-bisphosphate
      carboxylase/oxygenase was identified, while genes necessary for methanotrophy and
      for carboxysome formation were not identified. The N. oceani genome contains two
      copies each of the genes or operons necessary to assemble functional complexes I
      and IV as well as ATP synthase (one H(+)-dependent F(0)F(1) type, one Na(+)
      dependent V type).

PMID- 16957256
TI  - Application of a high-density oligonucleotide microarray approach to study
      bacterial population dynamics during uranium reduction and reoxidation.
AB  - Reduction of soluble uranium U(VI) to less-soluble uranium U(IV) is a promising
      approach to minimize migration from contaminated aquifers. It is generally
      assumed that, under constant reducing conditions, U(IV) is stable and immobile;
      however, in a previous study, we documented reoxidation of U(IV) under continuous
      reducing conditions (Wan et al., Environ. Sci. Technol. 2005, 39:6162-6169). To
      determine if changes in microbial community composition were a factor in U(IV)
      reoxidation, we employed a high-density phylogenetic DNA microarray (16S
      microarray) containing 500,000 probes to monitor changes in bacterial populations
      during this remediation process. Comparison of the 16S microarray with clone
      libraries demonstrated successful detection and classification of most clone
      groups. Analysis of the most dynamic groups of 16S rRNA gene amplicons detected
      by the 16S microarray identified five clusters of bacterial subfamilies
      responding in a similar manner. This approach demonstrated that amplicons of
      known metal-reducing bacteria such as Geothrix fermentans (confirmed by
      quantitative PCR) and those within the Geobacteraceae were abundant during U(VI)
      reduction and did not decline during the U(IV) reoxidation phase. Significantly,
      it appears that the observed reoxidation of uranium under reducing conditions
      occurred despite elevated microbial activity and the consistent presence of metal
      reducing bacteria. High-density phylogenetic microarrays constitute a powerful
      tool, enabling the detection and monitoring of a substantial portion of the
      microbial population in a routine, accurate, and reproducible manner.

PMID- 16957259
TI  - Detection of Enterobacter sakazakii in dried infant milk formula by cationic
      magnetic-bead capture.
AB  - Enterobacter sakazakii has been associated with life-threatening infections in
      premature low-birth-weight infants. Contaminated infant milk formula (IMF) has
      been implicated in cases of E. sakazakii meningitis. Quick and sensitive methods
      to detect low-level contamination sporadically present in IMF preparations would
      positively contribute towards risk reduction across the infant formula food
      chain. Here we report on the development of a simple method, combining charged
      separation and growth on selective agar, to detect E. sakazakii in IMF. This
      protocol can reliably detect 1 to 5 CFU of E. sakazakii in 500 g of IMF in less
      than 24 h.

PMID- 16957258
TI  - Microbial population dynamics associated with crude-oil biodegradation in diverse
      soils.
AB  - Soil bacterial population dynamics were examined in several crude-oil
      contaminated soils to identify those organisms associated with alkane degradation
      and to assess patterns in microbial response across disparate soils. Seven soil
      types obtained from six geographically distinct areas of the United States
      (Arizona, Oregon, Indiana, Virginia, Oklahoma, and Montana) were used in
      controlled contamination experiments containing 2% (wt/wt) crude oil spiked with
      [1-(14)C]hexadecane. Microbial populations present during hydrocarbon degradation
      were analyzed using both 16S rRNA gene sequence analysis and by traditional
      methods for cultivating hydrocarbon-oxidizing bacteria. After a 50-day
      incubation, all seven soils showed comparable hydrocarbon depletion, where >80%
      of added crude oil was depleted and approximately 40 to 70% of added
      [(14)C]hexadecane was converted to (14)CO(2). However, the initial rates of
      hydrocarbon depletion differed up to 10-fold, and preferential utilization of
      shorter-chain-length n-alkanes relative to longer-chain-length n-alkanes was
      observed in some soils. Distinct microbial populations developed, concomitant
      with crude-oil depletion. Phylogenetically diverse bacterial populations were
      selected across different soils, many of which were identical to hydrocarbon
      degrading isolates obtained from the same systems (e.g., Nocardioides albus,
      Collimonas sp., and Rhodococcus coprophilus). In several cases, soil type was
      shown to be an important determinant, defining specific microorganisms responding
      to hydrocarbon contamination. However, similar Rhodococcus erythropolis-like
      populations were observed in four of the seven soils and were the most common
      hydrocarbon-degrading organisms identified via cultivation.

PMID- 16957261
TI  - Multiple contributions of peroxisomal metabolic function to fungal pathogenicity
      in Colletotrichum lagenarium.
AB  - In Colletotrichum lagenarium, which is the causal agent of cucumber anthracnose,
      PEX6 is required for peroxisome biogenesis and appressorium-mediated infection.
      To verify the roles of peroxisome-associated metabolism in fungal pathogenicity,
      we isolated and functionally characterized ICL1 of C. lagenarium, which encodes
      isocitrate lyase involved in the glyoxylate cycle in peroxisomes. The icl1
      mutants failed to utilize fatty acids and acetate for growth. Although Icl1 has
      no typical peroxisomal targeting signals, expression analysis of the GFP-Icl1
      fusion protein indicated that Icl1 localizes in peroxisomes. These results
      indicate that the glyoxylate cycle that occurs inside the peroxisome is required
      for fatty acid and acetate metabolism for growth. Importantly, in contrast with
      the pex6 mutants that form nonmelanized appressoria, the icl1 mutants formed
      appressoria that were highly pigmented with melanin, suggesting that the
      glyoxylate cycle is not essential for melanin biosynthesis in appressoria.
      However, the icl1 mutants exhibited a severe reduction in virulence. Appressoria
      of the icl1 mutants failed to develop penetration hyphae in the host plant,
      suggesting that ICL1 is involved in host invasion. The addition of glucose
      partially restored virulence of the icl1 mutant. Heat shock treatment of the host
      plant also enabled the icl1 mutants to develop lesions, implying that the
      infection defect of the icl1 mutant is associated with plant defense. Together
      with the requirement of PEX6 for appressorial melanization, our findings suggest
      that peroxisomal metabolic pathways play functional roles in appressorial
      melanization and subsequent host invasion steps, and the latter step requires the
      glyoxylate cycle.

PMID- 16957260
TI  - Global molecular and morphological effects of 24-hour chromium(VI) exposure on
      Shewanella oneidensis MR-1.
AB  - The biological impact of 24-h ("chronic") chromium(VI) [Cr(VI) or chromate]
      exposure on Shewanella oneidensis MR-1 was assessed by analyzing cellular
      morphology as well as genome-wide differential gene and protein expression
      profiles. Cells challenged aerobically with an initial chromate concentration of
      0.3 mM in complex growth medium were compared to untreated control cells grown in
      the absence of chromate. At the 24-h time point at which cells were harvested for
      transcriptome and proteome analyses, no residual Cr(VI) was detected in the
      culture supernatant, thus suggesting the complete uptake and/or reduction of this
      metal by cells. In contrast to the untreated control cells, Cr(VI)-exposed cells
      formed apparently aseptate, nonmotile filaments that tended to aggregate.
      Transcriptome profiling and mass spectrometry-based proteomic characterization
      revealed that the principal molecular response to 24-h Cr(VI) exposure was the
      induction of prophage-related genes and their encoded products as well as a
      number of functionally undefined hypothetical genes that were located within the
      integrated phage regions of the MR-1 genome. In addition, genes with annotated
      functions in DNA metabolism, cell division, biosynthesis and degradation of the
      murein (peptidoglycan) sacculus, membrane response, and general environmental
      stress protection were upregulated, while genes encoding chemotaxis, motility,
      and transport/binding proteins were largely repressed under conditions of 24-h
      chromate treatment.

PMID- 16957263
TI  - Removal and inactivation of Staphylococcus epidermidis biofilms by electrolysis.
AB  - Bacterial biofilms were exposed to electrolysis by making the steel substratum an
      electrode in a circuit including a 6-V battery. These treatments resulted in
      killing (2.1-log reduction) and removal (4.0-log reduction) of viable cells at
      the anode and cathode, respectively, within a few minutes.

PMID- 16957262
TI  - Proteomic profiling and identification of immunodominant spore antigens of
      Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis.
AB  - Differentially expressed and immunogenic spore proteins of the Bacillus cereus
      group of bacteria, which includes Bacillus anthracis, Bacillus cereus, and
      Bacillus thuringiensis, were identified. Comparative proteomic profiling of their
      spore proteins distinguished the three species from each other as well as the
      virulent from the avirulent strains. A total of 458 proteins encoded by 232 open
      reading frames were identified by matrix-assisted laser desorption ionization
      time-of-flight mass spectrometry analysis for all the species. A number of highly
      expressed proteins, including elongation factor Tu (EF-Tu), elongation factor G,
      60-kDa chaperonin, enolase, pyruvate dehydrogenase complex, and others exist as
      charge variants on two-dimensional gels. These charge variants have similar
      masses but different isoelectric points. The majority of identified proteins have
      cellular roles associated with energy production, carbohydrate transport and
      metabolism, amino acid transport and metabolism, posttranslational modifications,
      and translation. Novel vaccine candidate proteins were identified using B.
      anthracis polyclonal antisera from humans postinfected with cutaneous anthrax.
      Fifteen immunoreactive proteins were identified in B. anthracis spores, whereas
      7, 14, and 7 immunoreactive proteins were identified for B. cereus and in the
      virulent and avirulent strains of B. thuringiensis spores, respectively. Some of
      the immunodominant antigens include charge variants of EF-Tu, glyceraldehyde-3
      phosphate dehydrogenase, dihydrolipoamide acetyltransferase, Delta-1-pyrroline-5
      carboxylate dehydrogenase, and a dihydrolipoamide dehydrogenase. Alanine racemase
      and neutral protease were uniquely immunogenic to B. anthracis. Comparative
      analysis of the spore immunome will be of significance for further nucleic acid-
      and immuno-based detection systems as well as next-generation vaccine
      development.

PMID- 16957264
TI  - Granadaene: proposed structure of the group B Streptococcus polyenic pigment.
AB  - The goal of this work was to determine the chemical nature of the red pigment
      produced by Streptococcus agalactiae, which has been thought to be a carotene. We
      extracted the pigment with 0.1 M KOH and purified it by column chromatography on
      Sephadex LH. Data from elemental analysis and mass and nuclear magnetic resonance
      spectra lead us to propose the structure to be that of a new ornithine rhamno
      polyene with 12 conjugated double bonds, to which we have assigned the trivial
      name granadaene.

PMID- 16957265
TI  - Molecular diversity, cultivation, and improved detection by fluorescent in situ
      hybridization of a dominant group of human gut bacteria related to Roseburia spp.
      or Eubacterium rectale.
AB  - Phylogenetic analysis was used to compare 16S rRNA sequences from 19 cultured
      human gut strains of Roseburia and Eubacterium rectale with 356 related sequences
      derived from clone libraries. The cultured strains were found to represent five
      of the six phylotypes identified. A new oligonucleotide probe, Rrec584, and the
      previous group probe Rint623, when used in conjunction with a new helper
      oligonucleotide, each recognized an average of 7% of bacteria detected by the
      eubacterial probe Eub338 in feces from 10 healthy volunteers. Most of the
      diversity within this important group of butyrate-producing gut bacteria can
      apparently be retrieved through cultivation.

PMID- 16957266
TI  - Cloning of a heavy-metal-binding protein derived from activated-sludge
      microorganisms.
AB  - A gene of the heavy-metal-binding protein (HMBP) was newly isolated from a
      genetic DNA library of activated-sludge microorganisms. HMBP was produced by
      transformed Escherichia coli, and the copper-binding ability of HMBP was
      confirmed. HMBP derived from activated sludge could be available as heavy metal
      adsorbents in water and wastewater treatments.

PMID- 16957267
TI  - Molecular epidemiology of echoviruses 11 and 13, based on an environmental
      surveillance conducted in Toyama Prefecture, 2002-2003.
AB  - Nineteen echovirus 11 (E11) and 12 E13 isolates were isolated from three rivers
      in Toyama Prefecture, Japan, during an environmental surveillance conducted from
      April 2002 to March 2003. The nucleotide sequences of E13 isolates were closely
      related to those from patients with aseptic meningitis, with less than 1.3%
      divergence in the VP1 region of the viral capsid gene, and belonged to the same
      clade responsible for a worldwide outbreak that started in 2000. In contrast, E11
      isolates were clustered into three genomic groups and were not closely related to
      echovirus strains isolated from patients. These results suggest that the
      combination of both virus isolation from environmental sources and phylogenetic
      analysis could be complementary assessment approaches to trace prevalent and
      minor circulating enteroviruses in the human population.

PMID- 16957268
TI  - Complementation of a Clostridium perfringens spo0A mutant with wild-type spo0A
      from other Clostridium species.
AB  - To evaluate whether C. perfringens can be used as a model organism for studying
      the sporulation process in other clostridia, C. perfringens spo0A mutant IH101
      was complemented with wild-type spo0A from four different Clostridium species.
      Wild-type spo0A from C. acetobutylicum or C. tetani, but not from C. botulinum or
      C. difficile, restored sporulation and enterotoxin production in IH101. The
      ability of spo0A from C. botulinum or C. difficile to complement the lack of
      spore formation in IH101 might be due, at least in part, to the low levels of
      spo0A transcription and Spo0A production.

PMID- 16957269
TI  - Identification and differentiation of Legionella pneumophila and Legionella spp.
      with real-time PCR targeting the 16S rRNA gene and species identification by mip
      sequencing.
AB  - Fluorescent resonance energy transfer probes targeting the 16S rRNA gene were
      constructed for a sensitive and specific real-time PCR for identification and
      differentiation of Legionella pneumophila from other Legionella spp. For
      identification of non-L. pneumophila spp. by direct amplicon sequencing, two
      conventional PCR assays targeting the mip gene were established.

PMID- 16957270
TI  - Cloning of the novel gene encoding beta-agarase C from a marine bacterium, Vibrio
      sp. strain PO-303, and characterization of the gene product.
AB  - The beta-agarase C gene (agaC) of a marine bacterium, Vibrio sp. strain PO-303,
      consisted of 1,437 bp encoding 478 amino acid residues. beta-Agarase C was
      identified as the first beta-agarase that cannot hydrolyze neoagarooctaose and
      smaller neoagarooligosaccharides and was assigned to a novel glycoside hydrolase
      family.

PMID- 16957271
TI  - Enzymatic activation of lysine 2,3-aminomutase from Porphyromonas gingivalis.
AB  - The development of lysine 2,3-aminomutase as a robust biocatalyst hinges on the
      development of an in vivo activation system to trigger catalysis. This is the
      first report to show that, in the absence of chemical reductants, lysine 2,3
      aminomutase activity is dependent upon the presence of flavodoxin, ferredoxin, or
      flavodoxin-NADP(+) reductase.

PMID- 16957272
TI  - Isolation and characterization of a new T-even bacteriophage, CEV1, and
      determination of its potential to reduce Escherichia coli O157:H7 levels in
      sheep.
AB  - Bacteriophage CEV1 was isolated from sheep resistant to Escherichia coli O157:H7
      colonization. In vitro, CEV1 efficiently infected E. coli O157:H7 grown both
      aerobically and anaerobically. In vivo, sheep receiving a single oral dose of
      CEV1 showed a 2-log-unit reduction in intestinal E. coli O157:H7 levels within 2
      days compared to levels in the controls.

PMID- 16957273
TI  - Organotin decomposition by pyochelin, secreted by Pseudomonas aeruginosa even in
      an iron-sufficient environment.
AB  - A triphenyltin (TPT)-decomposing strain, Pseudomonas aeruginosa CGMCC 1.860, was
      screened out. It secreted an unknown TPT-decomposing factor into the medium,
      later shown to be pyochelin, even in the presence of 100 muM iron. To our
      knowledge, this is the first report of organotin decomposition by pyochelin.

PMID- 16957274
TI  - Seleno-L-methionine is the predominant organic form of selenium in Cupriavidus
      metallidurans CH34 exposed to selenite or selenate.
AB  - The accumulated organic form of selenium previously detected by X-ray absorption
      near-edge structure (XANES) analyses in Cupriavidus metallidurans CH34 exposed to
      selenite or selenate was identified as seleno-l-methionine by coupling high
      performance liquid chromatography to inductively coupled plasma-mass
      spectrometry.

PMID- 16957275
TI  - Virulence of Serratia strains against Costelytra zealandica.
AB  - Strains of Serratia spp. showed a high level of virulence when injected into the
      hemocoel of larvae Costelytra zealandica, with Serratia entomophila, S.
      plymuthica, and S. marcescens showing significantly higher virulence than S.
      proteamaculans. Toxicity was independent of the amber disease-causing plasmid
      pADAP, suggesting a generalized Serratia toxin.

PMID- 16957276
TI  - Quorum sensing-disrupting brominated furanones protect the gnotobiotic brine
      shrimp Artemia franciscana from pathogenic Vibrio harveyi, Vibrio campbellii, and
      Vibrio parahaemolyticus isolates.
AB  - Autoinducer 2 (AI-2) quorum sensing was shown before to regulate the virulence of
      Vibrio harveyi towards the brine shrimp Artemia franciscana. In this study,
      several different pathogenic V. harveyi, Vibrio campbellii, and Vibrio
      parahaemolyticus isolates were shown to produce AI-2. Furthermore, disruption of
      AI-2 quorum sensing by a natural and a synthetic brominated furanone protected
      gnotobiotic Artemia from the pathogenic isolates in in vivo challenge tests.

PMID- 16957277
TI  - Molecular-beacon multiplex real-time PCR assay for detection of Vibrio cholerae.
AB  - A multiplex real-time PCR assay was developed using molecular beacons for the
      detection of Vibrio cholerae by targeting four important virulence and regulatory
      genes. The specificity and sensitivity of this assay, when tested with pure
      culture and spiked environmental water samples, were high, surpassing those of
      currently published PCR assays for the detection of this organism.

PMID- 16957279
TI  - An accurate fluorescent assay for quantifying the extent of RNA editing.
AB  - Recent data suggest that small differences in editing efficiency can have
      significant functional consequences. Here we present a fluorescent poisoned
      primer extension assay that is capable of distinguishing editing efficiency
      differences as low as 5%. For a poison-primer extension assay to be accurate, the
      extension product must stop at the intended base. Sometimes, however, it runs
      beyond. We tested the effect of specific enzyme-terminator combinations on the
      amount of run through. In the worst cases it accounted for 70% of the total
      signal, and in the best cases <5%. In addition, the specific base can affect run
      through, with G producing the least. The accuracy of the assay was demonstrated
      on templates derived from mixed plasmids and then verified on two biological
      substrates. Using either a K(+) channel mRNA that contains a site for adenosine
      deamination or an ndhB mRNA that contains a site for cytidine deamination, the
      editing efficiency predicted by the assay closely matched that predicted by bulk
      sequencing of individual cDNA clones. This assay should prove useful for
      analyzing small changes in editing efficiency or for quantifying single
      nucleotide polymorphisms.

PMID- 16957281
TI  - The secret lives of Dictyostelium.
AB  - Research on Dictyostelium has a long history, the trend of which has been to add
      cell biology, natural products, and evolutionary biology research to the
      traditional studies of development. The methods presented here and the recent
      publication of the genome present vast new opportunities.

PMID- 16957280
TI  - The abundance of the spliceosomal snRNPs is not limiting the splicing of U12-type
      introns.
AB  - The rate of excision of U12-type introns has been reported to be slower than that
      of U2-type introns, suggesting a rate-limiting bottleneck that could down
      regulate genes containing U12-type introns. The mechanistic reasons for this
      slower rate of intron excision are not known, but lower abundance of the U12-type
      snRNPs and slower rate of assembly or catalytic activity have been suggested. To
      investigate snRNP abundance we concentrated on the U4atac snRNA, which is the
      least abundant of the U12-type snRNAs and is limiting the formation of
      U4atac/U6atac complex. We identified mouse NIH-3T3 cell line isolates in which
      the level of both U4atac snRNA and U4atac/U6atac complexes is reduced to 10%-20%
      of the normal level. We used these cell lines to investigate splicing efficiency
      by transient transfection of a reporter gene containing a U12-type intron and by
      quantitative PCR analysis of endogenous genes. The splicing of the reporter U12
      type intron was very inefficient, but the activity could be restored by
      overexpression of U4atac snRNA. Using these U4atac-deficient NIH-3T3 cells, we
      confirmed the results of previous studies showing that U12-type introns of
      endogenous genes are, indeed, excised more slowly than U2-type introns, but we
      found that the rate did not differ from that measured in cells displaying normal
      levels of U4atac snRNA. Thus our results suggest that the cellular abundance of
      the snRNPs does not limit U12-type intron splicing under normal conditions.

PMID- 16957282
TI  - The Genome of Dictyostelium discoideum.
AB  - The Dictyostelium discoideum genome has been sequenced, assembled and annotated
      to a high degree of reliability. The parts-list of proteins and RNA encoded by
      the six chromosomes can now be accessed and analyzed. One of the initial
      surprises was the remarkably large number of genes that are shared with plants,
      animals, and fungi that must have been present in their common progenitor over a
      billion years ago. The genome encodes a total of about 10,300 proteins including
      protein families involved in cytoskeletal control, posttranslational protein
      modification, detoxification, secondary metabolism, cell adhesion, and signal
      transduction. The genome has a higher proportion of homopolymeric tracts and
      simple sequence repeats, such as [CAA]n, than most other genomes. Triplet repeats
      in translated regions produce the highest known proportion of polyglutamine
      tracts in any known proteome. Phylogenetic analyses based on complete proteomes
      confirm that the amoebozoa are a sister group to the animals and fungi, distinct
      from plants and early diverging species such as Leishmania, Plasmodium, or
      Giardia. The completed Dictyostelium sequence opens the door to large-scale
      functional exploration of its genome.

PMID- 16957283
TI  - The cDNA sequencing project.
AB  - The Dictyostelium discoideum cDNA sequencing project started in 1995, preceding
      the genome sequencing project. Altogether, 14 cDNA libraries, including full
      length ones, were constructed from five different stages of growth and asexual
      and sexual development, from which nearly 100,000 randomly chosen clones were
      sequenced to yield over 150,000 expressed sequence tags (ESTs). The data have
      been publicized online to facilitate clone distribution and collaboration using
      the whole clone set for microarray analyses. The EST reads were assembled to 6700
      independent genes, which constitute about 55% of the total estimated
      Dictyostelium genes. Utilization of wet and dry resources have contributed to the
      understanding of the genetic system controlling the multicellular development in
      Dictyostelium.

PMID- 16957278
TI  - Searching for IRES.
AB  - The cell has many ways to regulate the production of proteins. One mechanism is
      through the changes to the machinery of translation initiation. These alterations
      favor the translation of one subset of mRNAs over another. It was first shown
      that internal ribosome entry sites (IRESes) within viral RNA genomes allowed the
      production of viral proteins more efficiently than most of the host proteins. The
      RNA secondary structure of viral IRESes has sometimes been conserved between
      viral species even though the primary sequences differ. These structures are
      important for IRES function, but no similar structure conservation has yet to be
      shown in cellular IRES. With the advances in mathematical modeling and
      computational approaches to complex biological problems, is there a way to
      predict an IRES in a data set of unknown sequences? This review examines what is
      known about cellular IRES structures, as well as the data sets and tools
      available to examine this question. We find that the lengths, number of upstream
      AUGs, and %GC content of 5'-UTRs of the human transcriptome have a similar
      distribution to those of published IRES-containing UTRs. Although the UTRs
      containing IRESes are on the average longer, almost half of all 5'-UTRs are long
      enough to contain an IRES. Examination of the available RNA structure prediction
      software and RNA motif searching programs indicates that while these programs are
      useful tools to fine tune the empirically determined RNA secondary structure, the
      accuracy of de novo secondary structure prediction of large RNA molecules and
      subsequent identification of new IRES elements by computational approaches, is
      still not possible.

PMID- 16957284
TI  - dictyBase and the Dicty Stock Center.
AB  - dictyBase is the model organism database that houses all the sequence and
      associated data for Dictyostelium discoideum, including literature, researchers,
      and strains from the Dicty Stock Center. The database makes it possible to
      connect genes, proteins, and publications and is designed to address the needs of
      biologists and bioinformaticists alike. We provide tools for retrieving and
      analyzing data and strive to compile the highest quality, most up-to-date
      information. Here we will describe how to navigate the website and mine the
      extensive database to help users make optimal use of this invaluable resource.

PMID- 16957285
TI  - Analysis of gene expression using cDNA microarrays.
AB  - A DNA microarray consists of an orderly arrangement of DNA, cDNA, or
      oligonucleotide probes that represent individual genes of an organism. Today,
      microarrays are the most important tools used to analyze gene transcription on a
      large scale. Investigations reach from finding key genes in whole genomes to
      looking at overall patterns of gene expression. This provides a better
      understanding of the architecture of genetic regulatory networks and helps to
      identify those genes in the genome that are differentially expressed, e.g.,
      during cellular programs, in tumors or as the result of a treatment. The use of
      different fluorescent dyes allows mRNAs from two different sources (tissues,
      strains, or differently treated cells) to be labeled in different colors, mixed,
      and hybridized to the same array, which results in competitive binding of the
      target to the arrayed sequences. After hybridization and washing, the slide is
      scanned using two different wavelengths corresponding to the dyes used, and the
      intensity of the same spot in both channels is compared. This results in a
      measurement of the ratio of transcript levels for each gene represented on the
      array. In order to find significantly regulated genes, the resulting data are
      analyzed by different bioinformatic tools such as R and significance analysis of
      microarrays (SAM).

PMID- 16957286
TI  - Proteomic analysis of Dictyostelium discoideum.
AB  - The social amoeba Dictyostelium discoideum is already known as a model organism
      for a variety of cellular and molecular studies. Now that the genome sequencing
      project has been completed and different tools with which to overexpress or knock
      out genes are available, this species has also moved into the spotlight of
      functional genomics studies. Consequently, this genomic sequence information can
      now be exploited to realize D. discoideum proteomics projects. Here, we present
      validated protocols adapted for analysis of the D. discoideum proteome. The
      workflow described in this chapter comprises two-dimensional polyacrylamide gel
      electrophoresis for protein separation and peptide mass fingerprint (matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry) for
      protein identification.

PMID- 16957287
TI  - Cultivation, spore production, and mating.
AB  - Dictyostelium discoideum proliferates as solitary amoebae, constitutes
      multicellular structures called fruiting bodies, and mates to form macrocysts
      depending on environmental conditions. All of these processes can be easily
      induced in the laboratory. The amoebae are normally cultured with food bacteria,
      but the strains with mutations in axe loci can proliferate in nutrient media
      without bacteria. The strains can be stored either as spores or amoebae.
      Synchronous development of fruiting bodies is initiated by depleting the culture
      media or food bacteria. Synchronous development of macrocysts is achieved by
      mixing the cells of heterothallic strains separately cultured in darkness to
      induce the sexual maturation.

PMID- 16957288
TI  - Parasexual genetics using axenic cells.
AB  - Normally, vegetative Dictyostelium grow as haploid cells. Occasionally, two
      haploid cells fuse together during normal growth, forming a diploid cell
      containing both parental sets of chromosomes within a single nucleus. The diploid
      state is reasonably stable, and the growth, development, and general behavior of
      diploids are similar to their haploid parents. However, during normal growth of
      diploids, cells may spontaneously lose one copy of each chromosome at random and
      revert back to a haploid state containing a selection of chromosomes from both
      parents. This diploid cycle therefore allows nonsexual recombination between two
      different mutant strains. Diploid cells have multiple practical uses. They allow
      the generation of double and multiple knockouts, and are particularly useful for
      strains that are sick or difficult to generate using molecular genetics. They
      provide a means of manipulating genes that are lethal when disrupted in haploids.
      In diploids, it is possible to isolate heterozygous knockouts with no phenotype
      and then introduce a further mutant allele. These cells can then be segregated to
      yield haploid progeny with an effective gene replacement. Similarly, diploids
      made from different parent strains offer a means of examining the effects of
      different genetic backgrounds and overriding strain-specific phenotypes. A number
      of other uses are possible, making parasexual genetics potentially even more
      versatile.

PMID- 16957289
TI  - Slug phototaxis, thermotaxis, and spontaneous turning behavior.
AB  - Dictyostelium slug phototaxis and thermotaxis are readily assayed phenotypes that
      reflect with great sensitivity and specificity the interactions of environmental
      stimuli with morphogenetic signaling systems controlling the collective movement
      of slug cells. Methods are described for conducting and recording phototaxis,
      thermotaxis, and spontaneous turning experiments, although it is pointed out that
      spontaneous turning rates are not easily measured in most strains of molecular
      biological interest. Both phototaxis and thermotaxis can be assayed qualitatively
      for rapid screening of prospective mutants and quantitatively for detailed
      phenotypic analysis. Both types of assay are simple to conduct, but require care
      to avoid the potentially misleading effects of other factors such as cell density
      and extraneous thermal and chemical gradients that might influence slug behavior.
      The quantitative analysis and statistical testing of conclusions are carried out
      using directional statistics, because traditional statistical methods for linear
      data are inappropriate and potentially misleading when applied to directional
      data. The appropriate statistical methods are given for measuring maximum
      likelihood estimates and confidence intervals for the average direction (mu) and
      the accuracy of orientation (kappa) for unidirectional orientation, as well as
      the two preferred directions (+/-alpha) and accuracy of orientation in
      bidirectional phototaxis. In addition, tests for uniformity (kappa = 0), for
      equality of kappa in the two-sample and multisample cases, and for bidirectional
      phototaxis vs unidirectional phototaxis are described. These methods are readily
      implemented in the R environment for statistical computing and the functions
      required to do so are described and provided.

PMID- 16957290
TI  - Purification techniques of subcellular compartments for analytical and
      preparative purposes.
AB  - In the following protocols, broken cells are the starting material of all
      downstream purifications of functional organelles or intact subcellular
      membranes. The choice of the breakage method has direct and deep repercussions on
      the quality of subsequent steps. Breaking vegetative amoebae by shear stress with
      a steel ball cell cracker preserves the integrity of subcellular organelles and
      in particular that of lysosomes, the rupture of which is very deleterious to
      further purifications. In this chapter, we propose purification schemes for
      plasma membrane, nuclei, mitochondria, and endocytic compartments. Plasma
      membranes are purified without any cell coating by partition between aqueous
      polymer phases. Nuclei and mitochondria are purified by differential
      centrifugations in adequate buffer conditions. Endosomes are magnetically
      isolated after feeding the cells with colloidal iron dextran and phagosomes by
      flotation on a sucrose gradient after feeding amoebae with latex beads. As
      analytical approaches, we propose procedures to label the plasma membrane and the
      endo-lysosomal compartments by biotinylation and to separate early and late
      compartments on a Percoll gradient.

PMID- 16957291
TI  - Generation of multiple knockout mutants using the Cre-loxP system.
AB  - Dictyostelium discoideum is an exceptionally powerful system by which to study
      various aspects of modern cell and developmental biology. The completion of the
      genome sequencing project together with a high-efficiency of targeted gene
      disruption have enabled researchers to characterize many specific gene functions.
      However, as a result of many gene products with overlapping functions, there is
      great need to produce mutants carrying mutations in multiple genes. We have,
      therefore, developed a robust system and describe a protocol for the generation
      of multiple gene mutations in Dictyostelium by recycling the Blasticidin S
      selectable marker after transient expression of Cre recombinase.

PMID- 16957292
TI  - Restriction enzyme-mediated integration (REMI) mutagenesis.
AB  - A method for the integration of linear DNA into the Dictyostelium genome is
      described. Restriction enzyme-mediated integration, or REMI, involves the
      transformation of cells with a mixture of plasmid DNA, linearized with a
      restriction enzyme, along with a restriction enzyme that is capable of generating
      compatible cohesive ends in the genome. The enzyme stimulates integration of the
      DNA into cognate restriction sites in the chromosomes, usually as a single-copy
      insertion event and with little collateral damage to the genome. REMI has proven
      useful for genetic screens and for placing genetic and molecular markers at
      particular points in the genome. Over the past 15 yr, REMI has been used to
      identify hundreds of interesting genes based on their mutant phenotypes.

PMID- 16957293
TI  - RNA interference and antisense-mediated gene silencing in Dictyostelium.
AB  - Knockouts by homologous recombination are frequently used to investigate the
      function of genes in Dictyostelium and other organisms. Antisense-mediated gene
      silencing and RNA interference (RNAi) are convenient alternatives to reduce gene
      expression to different levels and to silence multigene families. We describe
      here the methods for efficient RNA interference in Dictyostelium and some useful
      mutant strains that enhance the success rate or may serve as convenient controls.
      We believe that it is helpful to also discuss failed attempts to optimize and
      expand the system because these are rarely discussed in the literature. In
      addition, a list of in silico and experimentally identified components in the
      RNAi and antisense pathway is presented.

PMID- 16957294
TI  - Application of fluorescent protein tags as reporters in live-cell imaging
      studies.
AB  - The advent of the "GFP technology" together with advances in digital imaging and
      microscopic techniques has revolutionized our view of the living cell.
      Genetically encoded fluorescent proteins have become widely used as markers in
      living cells. The application of these fluorescent proteins as noninvasive tags
      revealed new aspects of protein dynamics and the biological processes they
      regulate. The modification of naturally occurring fluorescent proteins as well as
      the identification of new fluorescent proteins now provide researchers with a
      variety of useful fluorescent markers suitable for all kind of investigations in
      live-cell imaging studies. This chapter provides an overview of the most widely
      used fluorescent proteins for the labeling of either individual proteins or
      compartments of Dictyostelium discoideum cells. Furthermore, aspects such as how
      to design a fusion protein as well as advantages and disadvantages of specific
      fluorescent proteins are discussed. Finally, a protocol from transformation to
      identification of positive clones is provided.

PMID- 16957295
TI  - Investigating gene expression: in situ hybridization and reporter genes.
AB  - Coordinated cell type differentiation is essential for morphogenesis during
      Dictyostelium development. The specification of different cell types and the
      regulation of temporal and spatial patterns of expression of cell type-specific
      genes are important problems currently being addressed in many laboratories.
      Besides, determination of gene expression patterns provides significant
      information in the characterization of developmental mutants. Cell type-specific
      probes and well characterized promoters are available that allow the
      identification of most cell types during Dictyostelium development. Expression
      patterns can be studied by whole-mount in situ messenger RNA (mRNA) detection and
      by the use of reporter genes under the control of specific promoters. The most
      common in situ hybridization technique, based on nonradioactive ribo-probes that
      are hybridized to fixed whole-mounts prepared at different developmental stages,
      is described. Several reporter genes have been used to characterize gene
      expression patterns and to determine functional promoter elements. The lacZ gene,
      coding for the beta-galactosidase enzyme, is the reporter most frequently used in
      Dictyostelium because both temporal- and spatial-patterns of expression can be
      easily determined. Generally used beta-galactosidase detection methods are
      described.

PMID- 16957296
TI  - Application of 2D and 3D DIAS to motion analysis of live cells in transmission
      and confocal microscopy imaging.
AB  - The chemotactic signal in Dictyostelium is a cAMP wave that is relayed over
      relatively large distances through a cell population during aggregation. Cells
      exhibit unique behaviors in response to the different spatial, temporal, and
      concentration components of the cAMP wave, suggesting that distinct signal
      transduction pathways are evoked in each of the various phases of the wave. For
      this reason, we designed a set of experimental protocols to test responses of
      normal and mutant Dictyostelium amoebae to the different components of a wave of
      chemoattractant. We then used computer-assisted two- (2D) and three-dimensional
      (3D) technologies (2D and 3D Dynamic Image Analysis System [DIAS]) for analysis
      of cells in the absence of a chemotactic signal (basic motile behavior) and in
      response to the temporal, spatial, and concentration components of the wave. As a
      result, we have elucidated parallel and independent pathways activated by
      specific phases of the cAMP wave. Likewise, human polymorphonuclear neutrophils
      (PMNs) respond to experimentally applied waves of the chemotactic peptide fMLP,
      and also exhibit discrete behavioral responses to the different phases. Using
      Dictyostelium as a paradigm, we applied our protocols to normal and diseased
      human PMNs and precisely defined a chemotactic defect. In this chapter, we
      describe methods for quantifying behaviors in Dictyostelium amoebae, PMNs, and
      other amoeboid cells using 2D and 3D DIAS. These methods are useful in the
      reconstruction and motion analysis of most migrating cells with transmitted
      and/or confocal microscopy.

PMID- 16957297
TI  - Using quantitative fluorescence microscopy and FRET imaging to measure
      spatiotemporal signaling events in single living cells.
AB  - The mechanisms that mediate how migratory eukaryotic cells amplify a shallow,
      extracellular chemoattractant gradient into a steep intracellular gradient of
      signaling components to guide chemotaxis remains unknown. To unravel these
      mechanisms, it is essential to quantitatively measure the spatiotemporal patterns
      of chemoattractant gradients, the dynamic movement of intracellular signaling
      pathway molecules, and the localized activation of these molecules in single
      living cells. Recent developments in live-cell fluorescence microscopy have
      permitted direct visualization and quantitative measurement of signal
      transduction events with high temporal and spatial resolution. Here, we outline
      fluorescence imaging methods to simultaneously visualize and quantitatively
      measure spatiotemporal changes in chemoattractant concentration by using the
      fluorescent tracer dye Alexa 594. Next, we provide a method to correlate the
      dynamic changes in ligand to the spatiotemporal changes in the second messenger
      phosphatidylinositol 3,4,5-triphosphate (PIP3) along the inner surface of the
      plasma membrane in live cells. Finally, we describe a fluorescence resonance
      energy transfer (FRET) method to determine the extent of heterotrimeric G protein
      activation in single living cells in response to various chemoattractant fields.

PMID- 16957298
TI  - Visualizing signaling and cell movement during the multicellular stages of
      dictyostelium development.
AB  - Time-lapse microscopy provides a powerful tool with which to study cell behavior
      during Dictyostelium development. On a macroscopic level, the overall cell
      movement patterns that give rise to the complex multicellular structures such as
      slugs and fruiting bodies can be studied together with the signal waves that
      coordinate cell movement. Using green fluorescent protein fusion proteins, it is
      also possible to visualize the cytoskeleton or signal transduction processes at
      high resolution in single cells in their multicellular environment.

PMID- 16957299
TI  - Under-agarose chemotaxis of Dictyostelium discoideum.
AB  - In the vegetative state, Dictyostelium amoebae are chemotactic toward pterins
      released by bacteria, whereas during multicellular development, they become
      chemotactic to endogenously produced cAMP. A variety of assays have been used to
      visualize and quantify chemotactic movement. Under-agarose chemotaxis provides a
      simple and flexible assay that permits high-resolution imaging and quantification
      of the motility behavior of individual cells and populations by both transmitted
      light and fluorescence microscopy. The assay requires cells to deform a solid but
      flexible matrix; therefore, it also provides a way to measure defects in the
      ability of mutant cells to move in these restrictive conditions.

PMID- 16957300
TI  - Optimized fixation and immunofluorescence staining methods for Dictyostelium
      cells.
AB  - Recent years have seen a powerful revival of fluorescence microscopy techniques,
      both to observe live cells and fixed objects. The limits of sensitivity,
      simultaneous detection of multiple chromophores, and spatial resolution have all
      been pushed to the extreme. Therefore, it is essential to improve in parallel the
      quality of the structural and antigenic preservation during fixation and
      immunostaining. Chemical fixations are broadly used but often lead to
      antigenicity loss and severe membrane damages, such as organelle vesiculation.
      They also must be followed by membrane permeabilization by detergents or
      solvents, which can lead to extensive extraction and cytosol leakage. Fixation
      with solvents bypasses the need for permeabilization, but when carried out at
      "high" temperatures, leads to severe extraction of soluble proteins and lipids
      and cytosol wash-out, and has therefore been used routinely to visualize the
      cytoskeleton. Here, we describe a few modifications to the common aldehyde
      fixation protocol that help decrease the usual artifacts induced by chemical
      fixation. Alternatively, new techniques have now been established that are based
      on rapid freezing using a variety of coolants followed by fixation in solvents at
      low temperature. We present detailed protocols and notes that allow the
      achievement of optimal preservation and permeabilization for both light and
      electron microscopy.

PMID- 16957301
TI  - Cryofixation methods for ultrastructural studies of Dictyostelium discoideum.
AB  - Cryopreservation methods, including rapid freezing, freeze-substitution, and low
      temperature embedment, lead to superior ultrastructural preservation compared
      with traditional fixation procedures. This is particularly true for the
      multicellular stages of Dictyostelium discoideum, in which the hydrophobic sheath
      that surrounds the structures causes delayed penetration by the already slow
      acting aqueous chemical fixatives, resulting in cell shape changes, loss of cell
      cell contacts, and changes in cell-matrix interactions. The surface tension
      effects of traditional fixation methods can also result in disruption of the
      delicate structures. Depth of freezing is often greater than expected because of
      the relatively dehydrated state of the multicellular structures. Variations in
      freeze-substitution solvents and embedment media can be employed to allow for
      antigenic preservation. Commercial instruments exist for most of the procedures,
      but excellent results can be obtained using inexpensive hand-crafted apparatus.

PMID- 16957302
TI  - Analysis of signal transduction: formation of cAMP, cGMP, and Ins(1,4,5)P3 in
      vivo and in vitro.
AB  - This chapter describes biochemical assays with which to analyze signal
      transduction from surface cAMP receptors via G proteins to the effector enzymes
      adenylyl cyclase, guanylyl cyclase, and phospholipase C. The cAMP-mediated
      formation of the second messengers cAMP, cGMP, and Ins(1,4,5)P3 in cells will
      provide information on the entire pathway; here, details on isotope-dilution
      assays, through which the concentrations of these second messengers can be
      determined, are offered. Subsequently, several assays that analyze specific parts
      of the sensory transduction pathway are described. The assays include equilibrium
      and nonequilibrium binding to surface cAMP receptors on cells and on isolated
      membranes. The interaction between the cAMP receptor and G proteins can be
      measured as GTPgammaS-mediated inhibition of cAMP-binding to the receptor, or as
      cAMP-mediated stimulation of GTPase activity or GTPgammaS-binding to G proteins.
      Finally, assays for the in vitro G protein-mediated activation of the effector
      enzymes adenylyl cyclase, guanylyl cyclase, and phospholipase C are described.

PMID- 16957303
TI  - Assaying chemotaxis of Dictyostelium cells.
AB  - Both prokaryote and eukaryote cells can sense and move up chemical concentration
      gradients (chemotax). As a means of finding food sources during vegetative
      growth, Dictyostelium discoideum naturally chemotaxes toward chemicals released
      by bacteria. As part of its developmental life cycle, D. discoideum chemotaxes
      towards cAMP. This chapter describes protocols for using Dictyostelium to
      understand the cell biology behind and the signaling events necessary for
      eukaryotic amoeboid chemotaxis. The chapter includes analyses of random cell
      motility, directed motility up chemical gradients, cellular responses to uniform
      chemoattractant exposure, and the utility of fluorescent probes for chemotaxis
      signaling events. Random cell motility in the absence of chemoattractant is
      analyzed to decipher the properties of self-organizing pseudopodia extension and
      retraction. Monitoring chemotaxis toward cAMP and folate allows the determination
      of signaling events required for sensing a chemical gradient and moving in a
      directed, persistent manner up the gradient. Uniform chemoattractant exposure is
      employed to elucidate the immediate intracellular responses to chemoattractant
      stimulation. Finally, analyzing cells expressing fluorescent fusion proteins is
      vital to elucidating the location of signaling events during chemotaxis.

PMID- 16957304
TI  - Characterization of cross-linked actin filament gels and bundles using
      birefringence and polarized light scattering.
AB  - Fundamental processes in the life of Dictyostelium, such as locomotion,
      endocytosis, cytokinesis, and morphogenesis, are mediated by the actin
      cytoskeleton, which is composed of actin, myosins, and numerous actin-binding
      proteins. An understanding of these processes at the molecular level will require
      characterization of the structure, function, and dynamics of the actin and actin
      binding proteins both in vivo and in vitro. Dictyostelium has more than a dozen
      actin cross-linking proteins that can mediate the formation of isotropic actin
      gels and/or anisotropic actin bundles. We describe the use of transmitted
      polarized light and polarized light scattering in studies of actin and actin
      binding proteins during formation of nematic, gelled, or bundled structures.
      These methods have allowed quantitative studies of the effects of actin filament
      length, the concentration of actin, and the concentration of the cross-linking
      protein on the formation of cross-linked actin structures. Such methods hold
      great promise for characterization of novel cross-linking proteins, and for
      interpretation of phenotypes from strains lacking or expressing altered forms of
      these proteins. These methods are also applicable to studies of other systems
      such as the interactions of microtubules and microtubule associated proteins.

PMID- 16957305
TI  - Quantitative and microscopic methods for studying the endocytic pathway.
AB  - Endocytosis is a process that is essential to the life of all eukaryotic cells.
      Laboratory strains of Dictyostelium are extremely efficient in the uptake of both
      particles and fluid. Many different cellular processes feed into the endocytic
      pathway, and many organelle-associated and cytoplasmic proteins, including the
      ones from the cytoskeleton, contribute to the efficiency of transit. Therefore
      mutants, especially in genes of unknown function, must be characterized regarding
      their endocytic performance. We describe the most common tools and protocols to
      visualize and quantify all of the individual steps in endocytic transit.

PMID- 16957306
TI  - Preparation of intact, highly purified phagosomes from Dictyostelium.
AB  - Phagocytosis plays a fundamental role in the immune system for the defense
      against invading microorganisms and the clearing of apoptotic and cancerous
      cells. The common amoeba Dictyostelium discoideum is a recognized model for
      professional immune phagocytes and is now commonly used to study host-pathogen
      interactions. Dictyostelium is genetically and biochemically tractable and is a
      most versatile experimental system. The classical protocol for purifying
      phagosomes formed by ingestion of latex beads particles has been adapted to
      Dictyostelium. It was improved in yield, purity, and synchronicity, allowing
      isolation of milligram amounts of phagosomal proteins and lipids. This method has
      been used successfully to highlight membrane trafficking and phagosome
      maturation. Here, we present a step-by-step protocol including detailed notes
      necessary for ensuring access to a large number of highly synchronized phagosomes
      of high purity and integrity.

PMID- 16957307
TI  - Assaying cell-cell adhesion.
AB  - A major feature in Dictyostelium development is the transition from the
      unicellular to the multicellular stage, a process brought about by chemotaxis and
      cell-cell adhesion. Growth-phase cells are weakly cohesive, whereas aggregation
      competent cells adhere strongly to each other. In addition, aggregating cells
      display an ethylenediamine tetraacetic acid (EDTA)-resistant form of adhesion,
      which is developmentally regulated. Measuring cell-cell adhesion can thus be a
      simple and convenient method by which to assess the developmental progression of
      cells, to characterize mutants, and to discriminate between development and
      functional defects in cell adhesion molecules or membrane-cytoskeletal
      interactions. A quantitative cell adhesion assay is obviously crucial for
      identifying novel cell adhesion factors.

PMID- 16957308
TI  - Periodic activation of ERK2 and partial involvement of G protein in ERK2
      activation by cAMP in Dictyostelium cells.
AB  - Intercellular signaling mediated by cAMP plays a pivotal role in coordinating
      cell movement into aggregates at the early stage of Dictyostelium development
      when the extracellular level of cAMP periodically changes at 6- to 7-min
      intervals. We have shown that MAP kinase ERK2 is activated via the cAMP receptor
      CAR1 in phase with this periodic change. This was revealed by assessing the level
      of ERK2 activation with immunoblots using two kinds of antibodies, commercially
      available anti-phospho-p44/p42 MAP-kinase antibody and anti-Dictyostelium ERK2
      antibody. In this chapter, we describe the methods we have used to assess the
      level of activated ERK2 and partial involvement of G protein in cAMP-induced ERK2
      activation.

PMID- 16957309
TI  - An improved method for Dictyostelium centrosome isolation.
AB  - The Dictyostelium dicoideum centrosome consists of a box-shaped, layered core
      structure surrounded by dense nodules embedded in amorphous material, which make
      up the so-called corona. Thus, it differs markedly from centriole-containing
      centrosomes in animal cells or the plaque structure of yeast spindle pole bodies.
      For a long time, purification of Dictyostelium centrosomes was hampered by its
      extraordinarily tight linkage to the nucleus, which resisted all attempts to
      dissociate centrosomes and nuclei without destruction of the centrosome itself.
      Fortunately, we were able to solve this problem, and have already published a
      centrosome isolation protocol that is based on treatment of nucleus/centrosome
      complexes with sodium pyrophosphate and shear forces, followed by centrosome
      isolation through sedimentation and filtration techniques. However, isolated
      centrosomes prepared according to this protocol still contained too many
      impurities to allow mass spectrometrical analyses. Here, we present an improved
      protocol for the isolation of Dictyostelium centrosomes that contain considerably
      less contaminations with cytosolic and nuclear proteins.

PMID- 16957310
TI  - Epigenetics in Dictyostelium.
AB  - Dictyostelium has a good potential to serve as a model for the study of chromatin
      function and epigenetic gene regulation. The organism bridges the complexity of
      higher eukaryotic systems and the simplicity of yeast in that it harbors pathways
      that are similar to the former and is accessible to genetic manipulation like the
      latter. The findings that, in contrast to previous assumptions, Dictyostelium DNA
      contains methylated cytosine and that the RNA interference machinery may be
      involved in chromatin remodeling, open up new avenues to investigate epigenetic
      aspects in one of the most simple developing organisms. The protocols in this
      chapter describe the more recent techniques established for other organisms, with
      an emphasis on special precautions for application in Dictyostelium.

PMID- 16957311
TI  - Dictyostelium discoideum as a model to study host-pathogen interactions.
AB  - Dictyostelium discoideum is a molecularly amenable host model system for several
      human pathogens, including Legionella pneumophila, Mycobacterium avium,
      Mycobacterium marinum, Pseudomonas aeruginosa, and Cryptococcus neoformans.
      Dictyostelium wild-type cells have proven useful in screening and identifying
      numerous bacterial und fungal virulence factors. Moreover, Dictyostelium mutant
      cells can be used to identify genetic host determinants of susceptibility and
      resistance to infections. Marker genes such as the green fluorescence protein
      (GFP) gene allow the in vivo monitoring of infection-relevant host factors. Here,
      we present methods that have already contributed to the deciphering of important
      aspects of the Dictyostelium-Legionella interaction. Moreover, the described
      phagocytosis assay, infection assay, and the confocal in vivo monitoring of GFP
      tagged host factors can easily be adapted to other host-pathogen interactions.

PMID- 16957312
TI  - Pharmacogenetics: defining the genetic basis of drug action and inositol
      trisphosphate analysis.
AB  - Medicinal drugs do not always have clearly understood mechanisms of action,
      especially as regards psychiatric treatment. Identification of genes involved in
      drug resistance is an important step toward elucidating the genetic basis of
      disease and the molecular mechanism of drug action. However, this approach is
      impractical in higher animals, as ablation and screening of every gene in an
      animal is not currently possible. Dictyostelium has proven a good model system
      for molecular pharmacological research as a result of its genetic tractability,
      ease of gene knockout, and creation of isogenic lines. In this system, we have
      identified genes that confer resistance to bipolar disorder drugs. This work has
      implicated inositol (1,4,5) trisphosphate (InsP3) signaling as a common mechanism
      of action for these drugs in patients.

PMID- 16957313
TI  - How to assess and study cell death in Dictyostelium discoideum.
AB  - In this chapter, we describe how to conveniently demonstrate, assess, and study
      cell death in Dictyostelium through simple cell culture, clonogenic tests, and
      photonic (with the help of staining techniques) and electronic microscopy. Cell
      death can be convniently generated using minor modifications of the monolayer
      technique of Rob Kay et al., and either wild-type HMX44A Dictyostelium cells or
      the corresponding atg1- autophagy gene mutant cells. Methods to follow cell death
      qualitatively and quantitatively facilitate detailed studies of vacuolar death in
      wild-type cells and of nonvacuolar, "condensed" death in atg1- mutant cells.

PMID- 16957314
TI  - Infrared temperature-jump study of the folding dynamics of alpha-helices and beta
      hairpins.
AB  - The laser-induced temperature-jump (T-jump) technique in conjunction with
      infrared spectroscopy provides a versatile means to study the early events in
      protein folding. Compared with the commonly used stopped-flow kinetic methods,
      the T-jump initiation technique offers a faster time resolution. It allows the
      study of protein folding processes occurring on the nanosecond-to-microsecond
      time-scales. In addition, infrared spectroscopy is a powerful tool for
      characterizing backbone conformation and dynamics. In this chapter, we mainly
      discuss the application of this technique to the study of the helix-coil
      transition dynamics and the mechanism of beta-hairpin formation.

PMID- 16957315
TI  - The use of high-pressure nuclear magnetic resonance to study protein folding.
AB  - Recent development of high-pressure cells for a variety of spectroscopic methods
      has enabled the use of pressure as one of the commonly used perturbations along
      with temperature and chemical perturbations to study folding/unfolding reactions
      of proteins. Although various high-pressure spectroscopy techniques have their
      own significance, high-pressure nuclear magnetic resonance (NMR) is unique in
      that it allows one to gain residue-specific and atom-detailed information from
      proteins under pressure. Furthermore, because of a peculiar volume property of a
      protein, high-pressure NMR allows one to obtain structural information of a
      protein in a wide conformational space from the bottom to the upper region of the
      folding funnel, giving structural reality for the "open" state of a protein
      proposed from hydrogen exchange. The method allows a link between equilibrium
      folding intermediates and the kinetic intermediates, and manifests a new view of
      proteins as dynamic entities amply fluctuating among the folded, intermediate,
      and unfolded sub ensembles. This chapter briefly summarizes the technique, the
      principle, and the ways to use high-pressure NMR for studying protein folding.

PMID- 16957316
TI  - Characterization of denatured proteins using residual dipolar couplings.
AB  - The conventional view of denatured proteins as random coils is being challenged
      by nuclear magnetic resonance (NMR) experiments that can measure the relative
      orientation of backbone segments with respect to each other in a distance
      independent manner. Known as the residual dipolar coupling (RDC), this NMR
      parameter is measurable on proteins that have been weakly aligned inside a NMR
      tube. The simple observation of dipolar couplings unequivocally establishes that
      a denatured protein is not a random coil. Structures of denatured states under
      differing experimental conditions can be compared by a simple scatter plot of the
      RDCs measured under each condition; direct structural interpretation, however, is
      much more problematic. Here some of the technical issues for achieving weak
      alignment of denatured proteins are addressed using three types of media:
      strained polyacrylamide gels, both neutral or highly charged, and neutral lipid
      liquid crystalline bicelles. All three alignment media are experimentally robust
      and compatible with 8 M urea and low pH, conditions frequently used to denature
      proteins.

PMID- 16957317
TI  - Characterizing residual structure in disordered protein States using nuclear
      magnetic resonance.
AB  - The importance of disordered protein states in biology is gaining recognition,
      and can be attributed in part to the participation of unfolded and partially
      folded states of globular proteins in normal and abnormal biological functions,
      such as protein translation, protein translocation, protein degradation, protein
      assembly, and protein aggregation (1-5). There is also a growing awareness that a
      significant fraction of gene products from various genomes, including the human
      genome, fall into a category that includes low complexity, low globularity, or
      intrinsically unstructured proteins (6-9). Unlike native states of globular
      proteins, disordered protein states, by definition, do not adopt a fixed
      structure that can be determined using classical high-resolution methods.
      Nevertheless, there has long been evidence that many disordered states contain
      detectable and significant residual or nascent structure (10-16). This structure
      has been found to be important for nucleating local structure, as well as
      mediating long range contacts upon either intramolecular folding to the native
      state (17-21) or intermolecular folding with specific binding partners (22-24),
      and is also predicted to influence intermolecular folding into structured
      aggregates (25,26). The primary tool for the characterization of such structure
      is high-resolution solution state nuclear magnetic resonance (NMR) spectroscopy.
      Advances in NMR instrumentation and methods have greatly facilitated this task
      and in principle can now be accomplished by those without extensive prior
      experience in NMR spectroscopy. This chapter describes how this can be
      accomplished.

PMID- 16957318
TI  - Population and structure determination of hidden folding intermediates by native
      state hydrogen exchange-directed protein engineering and nuclear magnetic
      resonance.
AB  - Structural characterization of folding intermediates has been one of the
      important steps toward understanding the mechanism of protein folding. However,
      it has been very difficult to obtain high-resolution structures of folding
      intermediates. Such results have become available only very recently. Here, we
      review a procedure that uses the native-state amide hydrogen exchange-directed
      protein engineering method to populate partially unfolded intermediates and
      multidimensional NMR to solve the high-resolution structures of the
      intermediates.

PMID- 16957319
TI  - Characterizing protein folding transition States using Psi-analysis.
AB  - We discuss the implementation of Psi-analysis for the structural characterization
      of protein folding transition states. In Psi-analysis, engineered bi-histidine
      metal ion binding sites are introduced at surface positions to stabilize
      secondary and tertiary structures. The addition of metal ions stabilizes the
      interaction between the two known histidines in a continuous fashion. Measuring
      the ratio of transition state stabilization to that of the native state provides
      information about the presence of the metal binding site in the transition state.
      Psi-Analysis uses noninvasive surface mutations and does not require specialized
      equipment, so it can be readily applied to characterize the folding of many
      proteins. As a result, this method can provide a wealth of high-resolution
      quantitative data for comparison with theoretical folding simulations.
      Additionally, investigations of other biological processes also may utilize metal
      binding sites and Psi-analysis to detect conformational events during catalysis,
      assembly, and function.

PMID- 16957320
TI  - Advances in the analysis of conformational transitions in peptides using
      differential scanning calorimetry.
AB  - Differential scanning calorimetry can measure the heat capacity of a
      protein/peptide solution over a range of temperatures at constant pressure, which
      is used to determine the enthalpy function of the system. There are several
      experimental factors that can have a significant impact on the determined
      enthalpy and subsequent derived thermodynamic parameters. These factors are
      discussed in terms of sample and instrument preparation, as well as data
      collection and analysis.

PMID- 16957321
TI  - Application of single molecule Forster resonance energy transfer to protein
      folding.
AB  - Protein folding is a process characterized by a large degree of conformational
      heterogeneity. In such cases, classical experimental methods yield only mean
      values, averaged over large ensembles of molecules. The microscopic distributions
      of conformations, trajectories, or sequences of events often remain unknown, and
      with them the underlying molecular mechanisms. Signal averaging can be avoided by
      observing individual molecules. A particularly versatile method is highly
      sensitive fluorescence detection. In combination with Forster resonance energy
      transfer, distances and conformational dynamics can be investigated in single
      molecules. This chapter introduces the practical aspects of applying this method
      to protein folding.

PMID- 16957322
TI  - Single molecule studies of protein folding using atomic force microscopy.
AB  - Atomic force microscopy (AFM) offers new insights into the ability of proteins to
      resist mechanical force. The technique has been opened up by the availability of
      easy-to-use instruments that are commercially available, so that the technique no
      longer relies on the need to build instruments in the lab. Indeed it may become
      common for AFM instruments to sit beside stopped-flow apparatus in protein
      folding laboratories. In this chapter, we describe the instrument set-up, the
      preparation of suitable protein substrate, and the collection of data. Data
      selection and analysis are more complex than for conventional stopped-flow
      ensemble studies, but offer new insights into the function of proteins in vivo.

PMID- 16957323
TI  - Using triplet-triplet energy transfer to measure conformational dynamics in
      polypeptide chains.
AB  - Intrachain diffusion processes play an important role in protein folding and
      function. In this chapter we discuss the application of triplet-triplet energy
      transfer to directly measure rate constants for intrachain contact formation in
      polypeptide chains. The photochemistry of triplet-triplet energy transfer is
      described, experimental prerequisites of the method are discussed, and a detailed
      description of the experimental protocols and data analysis is given.

PMID- 16957324
TI  - A hierarchical protein folding scheme based on the building block folding model.
AB  - The building block protein folding model states that the native protein structure
      is the product of a combinatorial assembly of relatively structurally independent
      contiguous parts of the protein that possess a hydrophobic core, i.e., building
      blocks (BBs). According to this model, our group proposed a three-stage scheme
      for a feasible time-wise semi ab-intio protein structure prediction. Given a
      protein sequence, at the first stage of the prediction scheme, we propose cutting
      the sequence into structurally assigned BBs. Next, we perform a combinatorial
      assembly and attempt to predict the relative three-dimensional arrangement of the
      BBs. In the third stage, we refine and rank the assemblies. The scheme has proven
      to be very promising in reducing the complexity of the protein folding problem
      and gaining insight into the protein folding process. In this chapter, we
      describe the different stages of the scheme and discuss a possible application of
      the model to protein design.

PMID- 16957325
TI  - Replica exchange molecular dynamics method for protein folding simulation.
AB  - Understanding protein folding is one of the most challenging problems remaining
      in molecular biology. In this chapter, a highly parallel replica exchange
      molecular dynamics (REMD) method and its application to protein folding are
      described. The REMD method couples molecular dynamics trajectories with a
      temperature exchange Monte Carlo process for efficient sampling of the
      conformational space. A series of replicas are run in parallel at temperatures
      ranging from the desired temperature to a high temperature at which the replica
      can easily surmount the energy barriers. From time to time the configurations of
      neighboring replicas are exchanged and this exchange is accepted or rejected
      based on a Metropolis acceptance criterion that guarantees the detailed balance.
      Two example protein systems, one alpha-helix and one beta-hairpin, are used as
      case studies to demonstrate the power of the algorithm. Up to 64 replicas of
      solvated protein systems are simulated in parallel over a wide range of
      temperatures. The simulation results show that the combined trajectories in
      temperature and configurational space allow a replica to overcome free energy
      barriers present at low temperatures. These large-scale simulations also reveal
      detailed results on folding mechanisms, intermediate state structures,
      thermodynamic properties, and the temperature dependences for both protein
      systems.

PMID- 16957326
TI  - Estimation of folding probabilities and phi values from molecular dynamics
      simulations of reversible Peptide folding.
AB  - Molecular dynamics simulations with an implicit model of the solvent have allowed
      to investigate the reversible folding of structured peptides. For a 20-residue
      antiparallel beta-sheet peptide, the simulation results have revealed multiple
      folding pathways. Moreover, the conformational heterogeneity of the denatured
      state has been shown to originate from high enthalpy, high entropy basins with
      fluctuating non-native secondary structure, as well as low enthalpy, low entropy
      traps. An efficient and simple approach to estimate folding probabilities from
      molecular dynamics simulations has allowed to isolate conformations in the
      transition state ensemble and to evaluate Phi values, i.e., the effects of
      mutations on the folding kinetics and thermodynamic stability. These molecular
      dynamics studies have provided evidence that, if interpreted by neglecting the
      non-native interactions, Phi values overestimate the amount of native-like
      structure in the transition state.

PMID- 16957328
TI  - Intermediates and transition states in protein folding.
AB  - The complex role played by intermediates is dissected using experimental data on
      apomyoglobin (apoMb), simple theoretical concepts, and simulations of kinetics of
      simple minimal off-lattice models. The folding of moderate-to-large-sized
      proteins often occurs through passage of an ensemble of intermediates. In the
      case of apoMb there is dominant kinetic intermediate I that also occurs at
      equilibrium. The cooperativity of transition of U<-->I (U represents the ensemble
      of unfolded states) in apoMb at pH 4.0 is determined not only by the sequence but
      also by the anion concentration. Point mutations can substantially alter the
      cooperativity of formation of I. Another class of intermediates arise owing to
      bottlenecks in the rugged energy landscape that arises from topological
      frustration. As a result of the rough energy landscape, folding is predicted to
      follow the kinetic partitioning mechanism (KPM). According to KPM a fraction of
      molecules reaches the native state rapidly, while the remaining fraction is
      kinetically trapped in intermediates. The folding of lysozyme at pH 5.5 follows
      KPM. Our perspective also shows that the fraction of fast folding trajectories
      can be altered by changing pH, for example. These observations are clearly
      illustrated in simple off-lattice models of proteins. The simulations show that
      equilibrium intermediates occur "on-pathway" and have substantial probability to
      be revisited after the native state is reached, while kinetic intermediates are
      almost never sampled after native state is reached. In addition, kinetic
      intermediates are higher in free energy than equilibrium intermediates. We also
      discuss the consequences of multiple routes and intermediates on the transition
      state ensemble (TSE) in folding. Whenever multiple routes to the native state
      dominate, Phi-values can be larger than unity or less than zero. There appears to
      be a relationship between the diversity of structures in the denatured state
      ensemble and the extent to which the TSE is plastic. Simulations of beta-hairpins
      are used to illustrate these ideas.

PMID- 16957327
TI  - Packing regularities in biological structures relate to their dynamics.
AB  - The high packing density inside proteins leads to certain geometric regularities
      and also is one of the most important contributors to the high extent of
      cooperativity manifested by proteins in their cohesive domain motions. The
      orientations between neighboring nonbonded residues in proteins substantially
      follow the similar geometric regularities, regardless of whether the residues are
      on the surface or buried, a direct result of hydrophobicity forces. These
      orientations are relatively fixed and correspond closely to small deformations
      from those of the face-centered cubic lattice, which is the way in which
      identical spheres pack at the highest density. Packing density also is related to
      the extent of conservation of residues, and we show this relationship for residue
      packing densities by averaging over a large sample or residue packings. There are
      three regimes: (1) over a broad range of packing densities the relationship
      between sequence entropy and inverse packing density is nearly linear, (2) over a
      limited range of low packing densities the sequence entropy is nearly constant,
      and (3) at extremely low packing densities the sequence entropy is highly
      variable. These packing results provide important justification for the simple
      elastic network models that have been shown for a large number of proteins to
      represent protein dynamics so successfully, even when the models are extremely
      coarse grained. Elastic network models for polymeric chains are simple and could
      be combined with these protein elastic networks to represent partially denatured
      parts of proteins. Finally, we show results of applications of the elastic
      network model to study the functional motions of the ribosome, based on its known
      structure. These results indicate expected correlations among its components for
      the step-wise processing steps in protein synthesis, and suggest ways to use
      these elastic network models to develop more detailed mechanisms, an important
      possibility because most experiments yield only static structures.

PMID- 16957329
TI  - Thinking the impossible: how to solve the protein folding problem with and
      without homologous structures and more.
AB  - Structure prediction of proteins is a difficult task as well as prediction of
      protein-protein interaction. When no homologous sequence with known structure is
      available for the target protein, search of distantly related proteins to the
      target may be done automatically (fold recognition/threading). However, there are
      difficult proteins for which still modeling on the basis of a putative scaffold
      is nearly impossible. In the following, we describe that for some specific
      examples, human expertise was able to derive alignments to proteins of similar
      function with the aid of machine learning-based methods specifically suited for
      predicting structural features. The manually curate search of putative templates
      was successful in generating low-resolution three-dimensional (3D) models in at
      least two cases: the human tissue transglutaminase and the alcohol dehydrogenase
      from Sulfolobus solfataricus. This is based on the structural comparison of the
      model with the 3D protein structure that became available after prediction. For
      protein-protein interaction, a knowledge-based method can give predictions of
      putative interaction patches on the protein surface; this feature may help in
      adding additional weight to specific nodes in nets of interacting proteins.

PMID- 16957330
TI  - Structure and stability of the alpha-helix: lessons for design.
AB  - The alpha-helix is the most abundant secondary structure in proteins. We now have
      an excellent understanding of the rules for helix formation because of
      experimental studies of helices in isolated peptides and within proteins,
      examination of helices in crystal structures, computer modeling and simulations,
      and theoretical work. Here we discuss structural features that are important for
      designing peptide helices, including amino acid preferences for interior and
      terminal positions, side chain interactions, disulfide bonding, metal binding,
      and phosphorylation. The solubility and stability of a potential design can be
      predicted with helical wheels and helix/coil theory, respectively. The helical
      content of a peptide is most often quantified by circular dichroism, so its use
      is discussed in detail.

PMID- 16957331
TI  - De novo design of monomeric beta-hairpin and beta-sheet peptides.
AB  - Since the first report in 1993 (JACS 115, 5887-5888) of a peptide able to form a
      monomeric beta-hairpin structure in aqueous solution, the design of peptides
      forming either beta-hairpins (two-stranded antiparallel beta-sheets) or three
      stranded antiparallel beta-sheets has become a field of intense interest. These
      studies have yielded great insights into the principles governing the stability
      and folding of beta-hairpins and antiparallel beta-sheets. This chapter reviews
      briefly those principles and describes a protocol for the de novo design of beta
      sheet-forming peptides based on them. Criteria to select appropriate turn and
      strand residues and to avoid aggregation are provided. Because nuclear magnetic
      resonance is the most appropriate technique to check the success of new designs,
      the nuclear magnetic resonance parameters characteristic of beta-hairpins and
      three-stranded antiparallel beta-sheets are given.

PMID- 16957332
TI  - De novo proteins from binary-patterned combinatorial libraries.
AB  - Combinatorial libraries of well-folded de novo proteins can provide a rich source
      of reagents for the isolation of novel molecules for biotechnology and medicine.
      To produce libraries containing an abundance of well-folded sequences, we have
      developed a method that incorporates both rational design and combinatorial
      diversity. Our method specifies the "binary patterning" of polar and nonpolar
      amino acids, but allows combinatorial diversity of amino acid side chains at each
      polar and nonpolar site in the sequence. Protein design by binary patterning is
      based on the premise that the appropriate arrangement of polar and nonpolar
      residues can direct a polypeptide chain to fold into amphipathic elements of
      secondary structures, which anneal together to form a desired tertiary structure.
      A designed binary pattern exploits the periodicities inherent in protein
      secondary structure, while allowing the identity of the side chain at each polar
      and non-polar position to be varied combinatorially. This chapter provides an
      overview of the considerations necessary to design binary patterned libraries of
      novel proteins.

PMID- 16957333
TI  - Non-protein amino acids in the design of secondary structure scaffolds.
AB  - The use of stereochemically constrained amino acids permits the design of short
      peptides as models for protein secondary structures. Amino acid residues that are
      restrained to a limited range of backbone torsion angles (phi-psi) may be used as
      folding nuclei in the design of helices and beta-hairpins. alpha-Amino-isobutyric
      acid (Aib) and related Calphaalpha dialkylated residues are strong promoters of
      helix formation, as exemplified by a large body of experimentally determined
      structures of helical peptides. DPro-Xxx sequences strongly favor type II' turn
      conformations, which serve to nucleate registered beta-hairpin formation.
      Appropriately positioned DPro-Xxx segments may be used to nucleate the formation
      of multistranded antiparallel beta-sheet structures. Mixed (alpha/beta) secondary
      structures can be generated by linking rigid modules of helices and beta
      hairpins. The approach of using stereochemically constrained residues promotes
      folding by limiting the local structural space at specific residues. Several
      aspects of secondary structure design are outlined in this chapter, along with
      commonly used methods of spectroscopic characterization.

PMID- 16957334
TI  - Design and synthesis of beta-peptides with biological activity.
AB  - beta-Peptides have been used as a platform for developing bioactive compounds
      with various types of bioactivity such as antimicrobial activity, cholesterol
      absorption inhibition, somatostatin receptor agonist, and hDM2 inhibition. These
      bioactive beta-peptides have been designed based on bioactive alpha-peptides.
      Three main strategies have been used to design bioactive beta-peptides: direct
      conversion of alpha-peptide sequences into beta-peptide sequences, placement of
      side chains to provide desirable distribution of physicochemical properties, and
      the grafting of proteinaceous side chains critical for bioactivity onto beta
      peptide structures. This chapter briefly discusses the various strategies
      employed to design bioactive beta-peptides, followed by protocols for the
      synthesis of N-alpha-fluorenylmethyloxycarbonyl (Fmoc)-protected beta3-amino
      acids from Fmoc-protected alpha-amino acids, and synthesis of beta-peptides by
      solid phase methods using Fmoc-based chemistry.

PMID- 16957335
TI  - Design of miniproteins by the transfer of active sites onto small-size scaffolds.
AB  - Natural miniproteins (e.g., animal toxins, protease inhibitors, defensins) can
      express specific and powerful biological activities by using a stable and minimal
      (<80 amino acids) structural motif. Artificial activities have been designed on
      these miniscaffolds by transferring previously identified protein active sites
      into regions structurally compatible with the site and permissive for sequence
      mutations. These newly designed miniproteins, presenting a specific and high
      activity within a small size and well-defined three-dimensional structure,
      represent novel tools in biology, biotechnology, and medical sciences, and are
      also useful intermediates to develop new therapeutic agents. The different steps
      used to design and characterize new bioactive miniproteins are here described in
      detail. Two successful examples are here reported. The first one is a metal
      binding miniprotein (MBP, 37 residues), which possesses a metal specificity
      resembling that of natural carbonic anhydrase; the second is a CD4 mimic (CD4M33,
      27 residues), which is a powerful inhibitor of HIV-1 entry but also a fully
      functional substitute of the human receptor CD4 and, hence, a potential component
      of an AIDS vaccine.

PMID- 16957336
TI  - Consensus design as a tool for engineering repeat proteins.
AB  - Repeat proteins were first identified because of their unusual primary structure,
      in which short amino acid sequences, typically between 20 and 40 residues, are
      repeated in tandem, often many times. After identification at the sequence level,
      the three-dimensional structures of representatives from several classes (e.g.,
      ankyrin, tetratricopeptide, leucine rich repeat) have been solved. The structures
      indeed reveal unusual, nonglobular structures, a linear "string" of the tandem
      motifs. Perhaps because of the large surface area that is presented as a
      consequence of such elongated structures, repeat domains are often involved in
      mediating protein-protein interactions. Here we udescribe methods of consensus
      based design and engineering of repeat proteins. We pay particular attention to
      the attributes of repeat proteins that make them well-suited to such approaches.
      In addition, we discuss practical issues related to producing and characterizing
      such designed proteins. We use the tetratricopeptide repeat, which is well
      studied in our group, to illustrate many ideas, but also draw comparisons to
      other work on repeat proteins, where relevant.

PMID- 16957337
TI  - Multiple sequence alignment as a guideline for protein engineering strategies.
AB  - Many proteins lack the thermodynamic stability and/or solubility that is required
      for their use in a desired application. For this reason, it can be advantageous
      to improve these qualities through rational protein engineering. An effective
      means for achieving this goal is to use sequence alignment analysis to select
      amino acid substitutions that are likely to increase the thermodynamic stability
      or solubility of a protein. Advantages of using this approach are that generally
      only a small number of substitutions need to be tested, these substitutions are
      rarely debilitating to protein function, and knowledge of the three-dimensional
      structure of the protein of interest is not required. This chapter will describe
      approaches that have been used to exploit the information contained in sequence
      alignments for the engineering of improved protein properties.

PMID- 16957338
TI  - Sequence search methods and scoring functions for the design of protein
      structures.
AB  - This chapter focuses on the methods developed for the automatic or semiautomatic
      design of protein structures. We present several algorithms for the exploration
      of the sequence space and scoring of the designed models. There are now several
      successful designs that have been achieved using these approaches such as the
      stabilization of a protein fold, the stabilization of a protein-protein complex
      interface, and the optimization of a protein function. A rapid presentation of
      the methodologies is followed by a detailed analysis of two test case studies.
      The first one deals with the redesign of a protein hydrophobic core and the
      second one with the stabilization of a protein structure through mutations at the
      surface. The different approaches are compared and the consistency of the
      predictions with the experimental data are discussed. All the programs tested in
      these protocols are freely available through the internet and may be applied to a
      wide range of design issues.

PMID- 16957339
TI  - Prediction of protein-protein interaction based on structure.
AB  - A great challenge in the proteomics and structural genomics era is to predict
      protein structure and function from sequence, including the identification of
      biological partners. The development of a procedure to construct position
      specific scoring matrices for the prediction and identification of sequences with
      putative significant affinity faces this challenge. The local and web
      applications used for sequence and structure search, sequence alignment, protein
      modeling, molecule edition and modification, and scoring matrices construction
      are described in detail. The methodology is based on the information contained in
      structural databases and takes into account the subtle conformational and
      sequence details that characterize different structures within a family. Using
      the matrices, the protein sequence databases can be easily scanned to locate
      putative partners of biological significance. The success of this methodology
      opens the way for the prediction of protein-protein interaction at genome scale.

PMID- 16957340
TI  - Electrostatic design of protein-protein association rates.
AB  - De novo design and redesign of proteins and protein complexes have made promising
      progress in recent years. Here, we give an overview of how to use available
      computer-based tools to design proteins to bind faster and tighter to their
      protein-complex partner by electrostatic optimization between the two proteins.
      Electrostatic optimization is possible because of the simple relation between the
      Debye-Huckel energy of interaction between a pair of proteins and their rate of
      association. This can be used for rapid, structure-based calculations of the
      electrostatic attraction between the two proteins in the complex. Using these
      principles, we developed two computer programs that predict the change in k(on),
      and as such the affinity, on introducing charged mutations. The two programs have
      a web interface that is available at <webref
      type="url">www.weizmann.ac.il/home/bcges/PARE.html</webref> and <webref
      type="url">http://bip.weizmann.ac.il/hypare</webref>. When mutations leading to
      charge optimization are introduced outside the physical binding site, the rate of
      dissociation is unchanged and therefore the change in k(on) parallels that of the
      affinity. This design method was evaluated on a number of different protein
      complexes resulting in binding rates and affinities of hundreds of fold faster
      and tighter compared to wild type. In this chapter, we demonstrate the procedure
      and go step by step over the methodology of using these programs for protein
      association design. Finally, the way to easily implement the principle of
      electrostatic design for any protein complex of choice is shown.

PMID- 16957341
TI  - Peptide model systems for amyloid fiber formation: design strategies and
      validation methods.
AB  - The rational understanding of the factors involved in the formation of amyloid
      deposits in tissue is fundamental to the identification of novel therapeutic
      strategies to prevent or cure pathological conditions such as Alzheimer's and
      Parkinson's disease or spongiform encephalopathies. Given the complexity of the
      molecular events driving protein self-association, a frequent strategy in the
      field has consisted of designing simplified model systems that facilitate the
      analysis of the elements that predispose polypeptides toward amyloid formation.
      In fact, these systems have provided very valuable knowledge on the determinants
      underlying structural transitions to the polymeric beta-sheet state present in
      amyloid fibers and more disordered aggregates. In this chapter, we will describe
      different approaches to obtain and design model systems for amyloidogenesis, as
      well as the methodologies that are typically used to validate them. We will also
      show how some of the general principles obtained from these studies can be
      applied for de novo design purposes and for the sequence-based identification of
      amyloidogenic stretches in proteins.

PMID- 16957342
TI  - Protein misfolding disorders and rational design of antimisfolding agents.
AB  - Compelling evidence strongly suggests that the conversion of a normal soluble
      protein into a beta-sheet-rich oligomeric structure and further fibril formation
      is the critical step in the pathogenesis of several human diseases, termed
      protein misfolding disorders. Therefore, a promising therapeutic strategy
      consists of the design of molecules that prevent the misfolding and aggregation
      of these proteins. In this chapter, we survey the mechanism of protein misfolding
      and some strategies to rationally produce inhibitors of this process.

PMID- 16957343
TI  - A review of current and future molecular diagnostic tests for use in the
      microbiology laboratory.
AB  - Nucleic acid-based diagnostics gradually are replacing or complementing culture
      based, biochemical, and immunological assays in routine microbiology
      laboratories. Similar to conventional tests, the first-generation
      deoxyribonucleic acid assays determined only a single analyte. Recent
      improvements in detection technologies have paved the way for the development of
      multiparameter assays using macroarrays or micro-arrays, while the introduction
      of closed-tube real-time polymerase chain reaction systems has resulted in the
      development of rapid microbial diagnostics with a reduced contamination risk. The
      use of these new molecular technologies is not restricted to detection and
      identification of microbial pathogens but also can be used for genotyping,
      allowing one to determine antibiotic resistance or to perform microbial
      fingerprinting.

PMID- 16957344
TI  - Overview of DNA purification for nucleic acid-based diagnostics from
      environmental and clinical samples.
AB  - Direct deoxyribonucleic acid (DNA)-based detection methods are crucial for future
      environmental monitoring and clinical diagnosis. In this chapter, we provide an
      overview of the various sample preparation approaches for bacteria for direct
      analyses (i.e., without culturing) in environmental and clinical samples. The
      issues of sampling, sample preservation, separation of the microorganisms from
      the environmental or clinical matrix, and DNA purification are covered. This
      chapter will focus on the advantages and the disadvantages of the methods
      available.

PMID- 16957345
TI  - Microarray-based detection of bacteria by on-chip PCR.
AB  - In this chapter, a protocol called on-chip polymerase chain reaction (PCR) is
      presented for the deoxyribonucleic acid (DNA) microarray-based detection of
      bacterial target sequences. On-chip PCR combines, in a single step, the
      conventional amplification of a target with a simultaneous, nested PCR round
      intended for target detection. While freely diffusible primers are deployed for
      amplification, the nested PCR is initiated by oligonucleotide primers bound to a
      solid phase. Thus, on-chip PCR allows the single-step amplification and
      characterization of a DNA sample as a result of separation in liquid and solid
      phase reactions. In contrast to conventional PCR, the reaction is performed
      directly on the flat surface of a glass slide that holds an array of covalently
      attached nested primers. The bacterial target DNA is amplified and probed using
      primers identifying either species-specific sequence regions of ribosomal DNA or
      unique bacterial target genes, such as virulence or resistance factors. The
      microarray is produced using standard spotting equipment with an array layout
      containing a high number of replicates. Fluorescence scanning of on-chip PCR
      slides allows the rapid detection of the target of interest. The protocol
      described herein will show how on-chip PCR can be used to detect and precisely
      identify DNA of bacterial origin.

PMID- 16957346
TI  - An array biosensor for detection of bacterial and toxic contaminants of foods.
AB  - The Naval Research Laboratory has developed an array-based biosensor system
      capable of detecting multiple pathogenic and toxic species in complex matrices.
      Sandwich fluoroimmunoassays are performed on the surface of a patterned
      microscope slide that acts as an optical waveguide. Fluorescence from
      immunocomplexes formed on the slide surface is excited using the evanescent
      field, an electromagnetic component of light, and the pattern of fluorescence is
      imaged using a charge-coupled device camera. Using the evanescent wave for
      excitation allows real-time imaging. Alternatively, a confocal scanner can also
      be used to detect and quantify fluorescent spots. A method for immobilizing
      capture antibodies, performing assays, and detecting bound targets is presented.

PMID- 16957347
TI  - Detection of Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus
      influenzae in blood and cerebrospinal fluid using fluorescence-based PCR.
AB  - The polymerase chain reaction (PCR) is a fundamental part of modern molecular
      biology. Fluorescence-based PCR methods also are now available, which enable
      rapid, specific, and sensitive assays for the amplification and analysis of
      deoxyribonucleic acid (DNA). These methods are performed in closed-tube format,
      thereby reducing the risk of contamination between stages. In addition, post-PCR
      processing, such as clean-up steps and gel electrophoresis, are eliminated as the
      results are read via an integrated fluorimeter. An example of this methodology is
      fluorescence-based PCR using dual-labeled probes, termed dual-labeled end-point
      fluorescence PCR. This method uses oligonucleotide probes that are dual-labeled
      with a reporter dye and quencher dye. The method has the advantage that DNA
      extraction, liquid handling, PCR, and analysis also can be fully automated. In
      this chapter, the simultaneous detection of Neisseria meningitidis, Streptococcus
      pneumoniae, and Haemophilus influenzae from clinical samples is described.

PMID- 16957348
TI  - Use of hybridization probes in a real-time PCR assay on the LightCycler for the
      detection of methicillin-resistant Staphylococcus aureus.
AB  - The rapid and accurate identification of methicillin-resistant Staphylococcus
      aureus (MRSA) is of great importance for the affected patient, the involved ward,
      and the microbiological laboratory. Resistance to methicillin is encoded by the
      mecA gene in S. aureus. Because routine laboratory diagnostics may be time
      consuming and because species differentiation encounters a variety of
      difficulties, molecular techniques detecting both the mecA and a S. aureus
      specific gene are used for rapid and accurate detection and identification of
      MRSA. Various protocols, including the manual extraction of DNA have been
      established. In this chapter, the identification of MRSA based on simultaneous
      detection of the mecA gene and the S. aureus-specific Sa442 DNA fragment using
      automated DNA extraction and real-time polymerase chain reaction is described.
      This method is an attractive alternative to labor-intensive manual protocols and
      can easily be incorporated into the diagnostic microbiology laboratory workflow,
      with the ability to obtain results within 4 h.

PMID- 16957349
TI  - Detection of verotoxin genes VT 1 and VT 2 in Escherichia coli O157:H7 in minced
      beef using immunocapture and real-time PCR.
AB  - Escherichia coli O157:H7 is a highly virulent pathogen that causes severe food
      poisoning in humans. Many outbreaks involving this pathogen have been linked to
      minced beef. A protocol is presented here to detect E. coli O157:H7 in minced
      beef. The method consists of an enrichment step in modified tryptone soya broth,
      followed by immunomagnetic separation and extraction of deoxyribonucleic acid.
      Real-time polymerase chain reaction, using hybridization probes, is used to
      detect the verotoxin genes 1 and 2 found in E. coli O157:H7. The assay has a
      detection limit of log10 3.5/mL E. coli O157:H7 cells in minced beef.

PMID- 16957350
TI  - Application of two-step quantitative reverse-transcription PCR to bacterial
      diagnostics.
AB  - Use of high copy number bacterial RNA offers several advantages in a diagnostics
      context compared with current deoxyribonucleic acid-based assays. The opportunity
      to only detect viable cells by targeting labile RNA transcripts may create an
      opportunity for "real-time" monitoring of pathogen load in response to a
      treatment regimen, while the natural amplification provided by the relative
      abundance of the RNA target compared with its corresponding gene opens a door to
      potential nonamplified direct detection technologies. In this chapter, a method
      is described to accurately quantify specific RNA transcripts and thus determine
      their potential utility as "high-copy" targets. The quantification method
      described also has application in gene-expression analysis.

PMID- 16957351
TI  - Quencher extension for single nucleotide polymorphism quantification in bacterial
      typing and microbial community analyses.
AB  - Quencher extension is a novel single-step closed tube real-time method to
      quantify single nucleotide polymorphisms (SNPs) in combination with primer
      extension. A probe with a 5'-reporter is single-base extended with a dideoxy
      nucleotide containing a quencher if the target SNP allele is present. The
      reaction is measured from the quenching (reduced fluorescence) of the reporter.
      The relative amount of a specific SNP allele is determined from the nucleotide
      incorporation rate in a thermocycling reaction. The quencher extension protocol
      presented was developed for SNP allele quantification in Listeria monocytogenes
      and for microbial community analyses.

PMID- 16957352
TI  - Amplified fragment-length polymorphism and protein profiling for identification
      of Campylobacter lari subgroups.
AB  - Amplified fragment-length polymorphism analysis (AFLP) has been shown to be a
      suitable method for subtyping of bacteria belonging to the genus Campylobacter.
      Campylobacter lari is a phenotypically and genotypically diverse species that
      comprises the classical nalidixic acid-resistant thermophilic campylobacters and
      the biochemical C. lari variants, urease-positive, nalidixic acid-susceptible,
      and urease producing nalidixic acid-susceptible strains. AFLP profiling and whole
      cell protein profile analysis are suitable methods for studying the taxonomic and
      epidemiological relationships among strains of the C. lari variants. Numerical
      analysis of AFLP profiles and of partial protein profiles allows the
      discrimination of distinct C. lari genogroups. No correlation of these genogroups
      with different sources of the strains has been identified until now.

PMID- 16957353
TI  - Use of peptide nucleic acid probes for rapid detection and enumeration of viable
      bacteria in recreational waters and beach sand.
AB  - Environmental monitoring and public health risk assessments require methods that
      are rapid and quantitative with defined sensitivity and specificity thresholds.
      Although several molecular techniques have been developed to rapidly detect
      bacteria in complex matrices, the challenge to simultaneously detect and
      enumerate only viable cells remains a limiting factor to their routine
      application. This chapter describes the use of peroxidase-labeled peptide nucleic
      acid (PNA) probes to simultaneously detect and count live Staphylococcus aureus,
      a human pathogen in sea water and beach sand. Mixed bacteria from the
      environmental sample were immobilized on polyvinylidene difluoride membrane
      filters and allowed to form microcolonies during a 5-h incubation on Tryptic soy
      agar plates. PNA probes targeting species-specific regions of the 16S rRNA
      sequences of S. aureus were then used to hybridize the target bacteria in situ.
      Probes were detected by capturing chemiluminiscence on instant (e.g., Polaroid)
      films. Each viable cell (i.e., rRNA producing) is detected as a light spot from
      its microcolony on the film after scanning the image into a computer. This rapid
      in situ hybridization technique is simple and highly sensitive and could be
      developed into portable kits for monitoring pathogens and indicators in the
      environment.

PMID- 16957354
TI  - HOOF prints: Brucella strain typing by PCR amplification of multilocus tandem
      repeat polymorphisms.
AB  - A critical component of limiting bacterial disease outbreaks is the tracing of
      the infection to the index source, which can be facilitated by using a highly
      discriminating bacterial identification system that will reliably identify
      genetically related bacterial populations. For pathogenic bacteria with highly
      conserved genomes, such as the zoonotic pathogen Brucella, finding distinguishing
      markers or traits for strain identification is challenging. This chapter
      describes a relatively new procedure for identifying Brucella strains. The
      procedure, which is called "HOOF prints" (hypervariable octameic oligonucleotide
      fingerprints), is based on high levels of polymorphism observed at several
      genomic loci in the Brucella genomes that contain small tandemly repeated
      deoxyribonucleic sequences. The technique described is designed for medium- to
      high-throughput analyses. However, the method described can be modified to
      characterize fewer samples.

PMID- 16957355
TI  - Detection of legionella in various sample types using whole-cell fluorescent in
      situ hybridization.
AB  - The human pathogenic Legionella bacteria are found ubiquitously in natural and
      human-made aquatic environments as residents in biofilms, where close
      interactions with other microorganisms like protozoa are possible. Nosocomial
      legionellosis already has been linked frequently to Legionella-contaminated
      artificial water supplies. For this reason, a rapid and accurate detection and
      quantification of these bacteria in environmental and clinical samples, combined
      with more information about their behavior in complex microbial communities and
      diverse ecosystems, is of importance. More insight into the ecology of the
      Legionella bacteria can lead to new methods to suppress their high numbers in
      human-made aquatic systems. Fluorescent in situ hybridization (FISH), based on
      ribosomal ribonucleic acid-targeted oligonucleotide probes, combines the
      precision and specificity of a molecular technique with the power to visualize
      individual cells without prior cultivation. In this chapter, the use of FISH for
      the detection and quantification of Legionella in water samples and in the
      visualization of these bacteria inside protozoa and biofilms is described in
      detail.

PMID- 16957356
TI  - Identification of diagnostic proteins in Mycobacterium avium subspecies
      paratuberculosis by a whole genome analysis approach.
AB  - Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is an
      economically significant veterinary pathogen that causes Johne's disease in
      cattle and sheep. There is a critical need for improved diagnostic tests to
      detect M. paratuberculosis infection in these animals. As with many other animal
      diseases, efforts need to be concentrated on the development of simple, rapid,
      noninvasive tests that can be performed by veterinarians or animal producers
      without expensive laboratory equipment. With the genome sequence of M.
      paratuberculosis now complete, we have taken a different strategy to identify
      novel proteins that are present uniquely in M. paratuberculosis and are antigenic
      in the context of infected cattle. Through a whole genome comparison of M.
      paratuberculosis with other sequenced mycobacterial genomes, we identified a
      collection of more than 90 genes that are present uniquely in M.
      paratuberculosis. This list has been further trimmed to 39 after amplification
      using polymerase chain reaction of unique genes using the genomic
      deoxyribonucleic acid template from several mycobacterial species and isolates. A
      selection of the remaining genes has been cloned and expressed in Escherichia
      coli and purified by affinity chromatography. Successfully purified proteins were
      analyzed using sera from rabbits immunized with M. paratuberculosis. Furthermore,
      to identify antigens in the context of disease, sera from cattle with Johne's
      disease as well as healthy control cattle are used in immunoassays. Using this
      methodology, we identified the first protein antigens specific to M.
      paratuberculosis.

PMID- 16957357
TI  - Diagnosis of Q fever using indirect microimmunofluorescence.
AB  - A microimmunofluorescence technique for the diagnosis of Q fever is described.
      Although this method is useful for serological diagnosis of Q fever, some
      technical difficulties are associated with it. First, the test antigens must be
      produced by a cell culture method in a level-3 biohazard facility and, second,
      the antigen Coxiella burnetii, which is the causative agent of Q, is
      characterized by the presence of two phases. To obtain phase I antigen, mice must
      be inoculated with C. burnetii. The materials obtained from the spleens of the
      infected mice are then used for cell inoculation. After purification, the
      antigens of both phases are deposited and fixed on multiple-well microscope
      slides. The serially diluted sera to be tested are incubated on these slides,
      then rinsed and overlaid with anti-IgG, -IgM and/or IgA secondary antibodies.
      Finally, the slides are examined under a fluorescence microscope for presence of
      C. burnetii.

PMID- 16957358
TI  - Macrophage cell cultures for rapid isolation of intracellular bacteria: the
      Mycobacterium bovis model.
AB  - Isolation of Mycobacterium bovis from suspected cases of bovine tuberculosis
      demands laborious and time-consuming procedures. Also, direct PCR procedures on
      tissue samples show poor sensitivity, whereas radiometric and fluorescence-based
      identification procedures demand high running costs and do not reduce the time
      needed for isolation to less than 10 to 15 d. Owing to the aforementioned
      obstacles, the human macrophage cell line THP-1 and other macrophage cell lines
      were investigated in experiments of M. bovis propagation and isolation from organ
      samples. Macrophage cells can support a high-titered propagation within 48 h of
      minute amounts of both BCG and fully pathogenic M. bovis strains from organ
      samples. A proper antibiotic mixture prevents contamination of cell cultures. A
      seminested PCR for tuberculosis complex-specific insertion sequence IS6110
      revealed M. bovis infection in infected cells. The same result can be obtained by
      a flow cytometry assay for expression of M. bovis chaperonin 10. The reduced time
      for isolation and identification of M. bovis (48-72 h) and the consistency of the
      test results make the use of macrophage cell lines attractive and cost-effective
      for veterinary laboratories involved in surveillance of bovine tuberculosis.

PMID- 16957363
TI  - The microRNA: overview of the RNA gene that modulates gene functions.
AB  - MicroRNAs (miRNAs), widely distributed, small regulatory RNA genes, target both
      messenger RNA (mRNA) degradation and suppression of protein translation based on
      sequence complementarity between the miRNA and its targeted mRNA. Different names
      have been used to describe various types of miRNA. During evolution, RNA
      retroviruses or transgenes invaded the eukaryotic genome and inserted itself in
      the noncoding regions of DNA, conceivably acting as transposon-like jumping
      genes, providing defense from viral invasion and fine-tuning of gene expression
      as a secondary level of gene modulation in eukaryotes. When a transposon is
      inserted in the intron, it becomes an intronic miRNA, taking advantage of the
      protein synthesis machinery, i.e., mRNA transcription and splicing, as a means
      for processing and maturation. Recently, miRNAs have been found to play an
      important, but not life-threatening, role in embryonic development. They might
      play a pivotal role in diverse biological systems in various organisms,
      facilitating a quick response and accurate plotting of body physiology and
      structures. Based on these unique properties, manufactured intronic miRNAs have
      been developed for in vitro evaluation of gene function, in vivo gene therapy,
      and generation of transgenic animal models. The biogenesis and identification of
      miRNAs, potential applications, and future directions for research are presented
      in this chapter, hopefully providing a guideline for further miRNA and gene
      function studies.

PMID- 16957364
TI  - Structure analysis of microRNA precursors.
AB  - MicroRNA biogenesis occurs in several steps from their precursors having
      irregular hairpin structures. The highly variable architecture of these stem-and
      loop structures, which have terminal loops of various sizes and diverse structure
      destabilizing motifs present in their stem sections, may strongly influence the
      process of microRNA liberation. In order to better understand this process, more
      details regarding its structural basis are required. A substantial part of this
      information may be derived from the structure analysis of microRNA precursor
      using biochemical methods. Here we show how the analysis with the use of various
      nucleases and metal ions is performed. The presented protocols include the design
      of DNA template-phage promoter fusions to generate natural precursor ends, and
      the tests performed to check the sequence and structure homogeneity of the in
      vitro transcripts prior to probing their structures.

PMID- 16957365
TI  - MicroRNA biogenesis: isolation and characterization of the microprocessor
      complex.
AB  - The recently discovered microRNAs (miRNAs) are a large family of small regulatory
      RNAs that have been implicated in controlling diverse pathways in a variety of
      organisms (1, 2). For posttranscriptional gene silencing, one strand of the miRNA
      is used to guide components of the RNA interference machinery, including
      Argonaute 2, to messenger RNAs (mRNAs) with complementary sequences (3, 4). Thus,
      targeted mRNAs are either cleaved by the endonuclease Argonaute 2 (5, 6), or
      protein synthesis is blocked by an as yet uncharacterized mechanism (7, 8). Genes
      encoding miRNAs are transcribed as long primary miRNAs (pri-miRNAs) that are
      sequentially processed by components of the nucleus and cytoplasm to yield a
      mature, approx 22-nucleotide (nt)-long miRNA (9). Two members of the ribonuclease
      (RNase) III endonuclease protein family, Drosha and Dicer, have been implicated
      in this two-step processing (10-13). To further our understanding of miRNA
      biogenesis and function it will be essential to identify the protein complexes
      involved. We were interested in defining the proteins required for the initial
      nuclear processing of pri-miRNAs to the approx 60- to 70-nt stem-loop
      intermediates known as precursor miRNAs (pre-miRNAs) (9, 10). This led to our
      identification of a protein complex we termed Microprocessor, which is necessary
      and sufficient for processing pri-miRNA to premiRNAs (14). The Microprocessor
      complex comprises Drosha and the double-stranded RNAbinding protein DiGeorge
      syndrome critical region 8 gene (DGCR8), which is deleted in DiGeorge syndrome
      (15, 16). In this chapter, we detail the methods used for the biochemical
      isolation and identification of the Microprocessor complex from human cells. We
      include a protocol for the in vitro analysis of pri-miRNA processing activity of
      the purified Microprocessor complex.

PMID- 16957366
TI  - Recognition and cleavage of primary microRNA transcripts.
AB  - MicroRNAs (miRNAs) are approx 22-nucleotide (nt)-long, single-stranded,
      endogenous, noncoding RNAs that are widely expressed in multicellular organisms.
      This chapter describes methods that allow the overexpression of human miRNAs and
      also discusses how primary miRNAs (pri-miRNAs), the much longer precursors of
      mature miRNAs, are processed in human cells, as well as in vitro.

PMID- 16957367
TI  - Mouse embryonic stem cells as a model genetic system to dissect and exploit the
      RNA interference machinery.
AB  - Conditional gene targeting is often a useful approach to elucidate the in vivo
      function of a gene. We use this approach to investigate the biological role of
      the RNA interference (RNAi) pathway in mammals. In addition, the RNAi machinery
      in mammalian cells can be exploited for gene knock-down experiments. In this
      chapter, we discuss the variety of experiments that can be performed using
      genetically engineered embryonic stem (ES) cells. ES cells provide a mammalian
      genetic system that is physiological, and tractable for mutagenesis and
      experimentation. This approach is economical and rapid, because it does not
      require production and breeding of genetically engineered mice.

PMID- 16957368
TI  - MicroRNAs and messenger RNA turnover.
AB  - Although initially believed to act exclusively as translational repressors,
      microRNAs (miRNAs) are now known to target complementary messenger RNA (mRNA)
      transcripts for either translational repression or cleavage via the RNA-induced
      silencing complex (RISC) ([1], reviewed in ref. 2). The current model postulates
      that mature miRNAs are incorporated into the RISC, bind target mRNAs based on
      complementarity, and guide cleavage of mRNA targets with perfect or nearly
      perfect complementarity and translational repression of targets with lower
      complementarity (2). The translational repression mechanism of miRNA-mediated
      gene regulation, which is common in animals but also exists in plants, is not
      well understood mechanistically. Conversely, miRNA-directed mRNA cleavage by RISC
      is common in plants, but also occurs in animals (3). This chapter focuses on the
      mRNA cleavage by miRNA-programmed RISC, and, specifically, on characterizing the
      products of such cleavage.

PMID- 16957369
TI  - Prediction of microRNA targets.
AB  - I describe the use of RNAhybrid, a program that predicts multiple potential
      binding sites of microRNAs (miRNAs) in large target RNAs. The core algorithm
      finds the energetically most favorable hybridization sites of a miRNA in a large
      potential target RNA. Intramolecular hybridizations, i.e., base pairings between
      target nucleotides or between miRNA nucleotides are, not allowed. For large
      targets, the time complexity of the algorithm is linear in the target length,
      allowing many long targets to be searched in a short time. Starting from the
      observation that the binding energies are results from an optimization procedure,
      we can model them as following an extreme value distribution. From this, we can
      calculate the statistical significance of individual binding sites, of multiple
      binding sites in a single target sequence, and of binding sites in comparative
      analyses of orthologous sequences across species. The latter involves the
      calculation of the effective number of orthologous sequences, which can be
      considerably smaller than the actual number, reflecting the statistical
      dependence of evolutionarily related sequences.

PMID- 16957370
TI  - Prediction of human microRNA targets.
AB  - MicroRNAs (miRNAs) are small, nonprotein-coding RNAs that regulate gene
      expression. Although hundreds of human miRNA genes have been discovered, the
      functions of most of these are unknown. Computational predictions indicate that
      miRNAs, which account for at least 1% of human protein-coding genes, regulate
      protein production for thousands of or possibly all of human genes. We discuss
      the functions of mammalian miRNAs and the experimental and computational methods
      used to detect and predict human miRNA target genes. Anticipating their impact on
      genome-wide discovery of miRNA targets, we describe the various computational
      tools and web-based resources available to predict miRNA targets.

PMID- 16957371
TI  - Complications in mammalian microRNA target prediction.
AB  - In this chapter, we review evidence that at least three different types of
      microRNA (miRNA)-messenger RNA (mRNA) target interactions exist in mammals: short
      seeds, long seeds, and "perfect" hits (allowing G:U matches). Because new types
      of miRNAs are still being discovered, this list may not yet be complete.

PMID- 16957372
TI  - miRBase: the microRNA sequence database.
AB  - The miRBase Sequence database is the primary repository for published microRNA
      (miRNA) sequence and annotation data. miRBase provides a user-friendly web
      interface for miRNA data, allowing the user to search using key words or
      sequences, trace links to the primary literature referencing the miRNA
      discoveries, analyze genomic coordinates and context, and mine relationships
      between miRNA sequences. miRBase also provides a confidential gene-naming
      service, assigning official miRNA names to novel genes before their publication.
      The methods outlined in this chapter describe these functions. miRBase is freely
      available to all at http://microrna.sanger.ac.uk/.

PMID- 16957373
TI  - Methodologies for high-throughput expression profiling of microRNAs.
AB  - MicroRNAs (miRNAs) have recently emerged as important regulators of gene
      expression controlling central biological processes. These small, approx 22
      nucleotide (nt)-long RNA molecules induce translational suppression when they are
      imperfectly matched to their target messenger RNA (mRNA) or direct mRNA cleavage
      when perfectly, or nearly perfectly, matched to their target. Direct roles in
      developmental processes have been described in a variety of species, and
      involvement in human diseases, such as cancer and diabetes, has been implied.
      These studies highlight the need to obtain detailed expression profiles of miRNAs
      in tissues, during development, and in disease. Their small size and the
      existence of miRNA families of related sequences pose critical problems in
      approaching expression analysis of miRNAs, especially using high-throughput
      approaches. All methodologies presented here address the special requirements for
      the analysis of miRNA expression using a variety of platforms, including cloning,
      microarrays, and microbeads. The different variables, as well as the different
      approaches, used by various laboratories are detailed and general recommendations
      are provided.

PMID- 16957374
TI  - In situ hybridization as a tool to study the role of microRNAs in plant
      development.
AB  - MicroRNAs (miRNAs) have a vital role in the generation of plant forms through
      post-transcriptional regulation of the accumulation of developmental regulators.
      Analysis of their roles requires detailed knowledge of their expression patterns.
      We describe an in situ hybridization technique we have used to study the patterns
      of miRNA accumulation in Arabidopsis and in maize.

PMID- 16957375
TI  - Usefulness of the luciferase reporter system to test the efficacy of siRNA.
AB  - Small interefence RNA (siRNA) has revamped the technology of gene silencing in
      cultured mammalian cells after its first demonstration by Tushl et al. 4 yr ago.
      To circumvent the cost and the inconvenience in identifying a unique siRNA duplex
      that can quench target gene expression, we devised a reporter-based system to
      test knockdown efficiency of selected siRNAs. We demonstrated that this
      luciferase-based siRNA testing system can be used to evaluate the knockdown
      efficiency of a directly transfected siRNA duplex or an siRNA expressed from a
      lentiviral vector.

PMID- 16957376
TI  - Cloning microRNAs from mammalian tissues.
AB  - MicroRNAs (miRNAs) are ubiquitous regulators of gene expression in plants and
      animals. Their distinctive structure, as very short RNAs with a 5'-phosphate and
      3'-hydroxyl group, has enabled the development of protocols to clone miRNAs.
      After enrichment of these small molecules by size, serial ligation of adapter
      oligonucleotides to each terminus allows amplification using reverse
      transcription (RT)-polymerase chain reaction (PCR). Plasmid cloning of multiple
      miRNA sequences and subsequent DNA sequence analysis enable both bioinformatic
      characterization of the various miRNAs and experimental validation of their
      accumulation in cells.

PMID- 16957377
TI  - Methods for analyzing microRNA expression and function during hematopoietic
      lineage differentiation.
AB  - MicroRNAs (miRNAs), an abundant class of approx 22-nucleotide (nt) small RNAs
      that control gene expression at the posttranscriptional level, may play important
      roles during normal hematopoiesis and leukemogenesis. This chapter focuses on the
      methods and strategies for dissecting miRNA function during hematopoietic lineage
      differentiation. We describe a modified miRNA cloning method and expression
      analysis approach for determining miRNA expression during hematopoietic lineage
      differentiation. We illustrate a retroviral vector and a general strategy for the
      ectopic expression of miRNAs in hemato-poietic stem/progenitor cells. We discuss
      in vitro and in vivo functional assays that can be used to examine the roles of
      miRNAs during hematopoietic lineage differentiation. The methods and principles
      described here should also be applicable to study the roles of miRNAs in the
      differentiation and function of nonhematopoietic cell types.

PMID- 16957378
TI  - Identifying microRNA regulators of cell death in Drosophila.
AB  - Animal genomes contain on the order of at least hundreds of microRNAs (miRNAs).
      Although most remain uncharacterized, it is already clear that miRNAs regulate
      many biological processes. A number of Drosophila miRNAs have been identified as
      likely cell death regulators, but functions for most have simply not been
      explored. Here we describe a protocol for identifying miRNAs that can act as cell
      death regulators. We also describe a simple protocol for testing roles for mRNAs
      identified as candidate miRNA targets using computational or other approaches.

PMID- 16957379
TI  - MicroRNAs in human immunodeficiency virus-1 infection.
AB  - Initially reported for Caenorhabditis elegans, microRNA (miRNA) has been shown to
      regulate gene expression in plants, flies, and mammals . Here, we report on our
      approaches to investigate the role of miRNAs in human immunodeficiency virus
      (HIV)-1 infection. Using computer-directed foldings, we first identify potential
      sequences in HIV-1 that putatively encode miRNAs. Subsequently, we use Northern
      blotting of RNAs isolated from HIV-infected cells to confirm expression of
      predicted miRNA sequences. Finally, we use a scanning algorithm to search 3'
      untranslated regions (UTRs) of human messenger RNAs (mRNAs) in the attempt to
      predict potential sites targeted by HIV-1 miRNAs.

PMID- 16957380
TI  - Cloning and detection of HIV-1-encoded microRNA.
AB  - MicroRNAs (miRNAs) are 21-to 25-nucleotides (nt) long and interact with messenger
      RNAs to trigger either translational repression or RNA cleavage through RNA
      interference (RNAi). We have shown that HIV-1 nef double-stranded RNA from AIDS
      patients who are long-term nonprogressors, inhibits HIV-1 transcription; and that
      nef-derived miRNA, miR-N367, is produced in human T-cells persistently infected
      with HIV-1. The miR-N367 can block HIV-1 Nef expression and long terminal repeat
      (LTR) transcription, suggesting that miR-N367 might suppress both Nef function
      and HIV-1 transcription through the RNAi pathway. Protocols are presented here
      for cloning HIV-1-encoded miRNA and confirming miRNA expression by Northern blot
      hybridization.

PMID- 16957381
TI  - Identification of messenger RNAs and microRNAs associated with fragile X mental
      retardation protein.
AB  - Fragile X syndrome, a common form of inherited mental retardation, is caused by
      the loss of the Fragile X mental retardation protein (FMRP). FMRP, which may
      regulate translation in neurons, not only associates with specific messenger RNAs
      (mRNAs) and with microRNAs (miRNAs), but also associates with the components of
      the miRNA pathway, including the Dicer and Argonaute proteins. It has been
      proposed that FMRP regulates the translation of its mRNA targets through miRNAs.
      In this chapter, we describe the protocol to identify the mRNAs and miRNAs
      associated with FMRP in vivo. The same method could also be applied to other RNA
      binding proteins interacting with specific mRNAs or miRNAs.

PMID- 16957382
TI  - In vitro precursor microRNA processing assays using Drosophila Schneider-2 cell
      lysates.
AB  - Recent studies have shown that the microRNA (miRNA) pathway is an evolutionarily
      conserved endogenous pathway that is important for normal development. Mature
      miRNAs are excised from precursors in a stepwise process and subsequently
      incorporated into an RNA-induced silencing complex (RISC), which mediates either
      cleavage of the target messenger RNA (mRNA) or translational repression,
      depending on the complementarity between the miRNA and its target mRNA. In this
      chapter, we describe in vitro precursor (pre)-miRNA processing assays using
      Drosophila Schneider-2 (S2) cell lysates and immunopurified materials.

PMID- 16957383
TI  - Downregulation of human Cdc6 protein using a lentivirus RNA interference
      expression vector.
AB  - Eukaryotic CDC6 gene function is required for the initiation of DNA replication
      and is a key regulatory protein during cell cycle progression. The human CDC6
      gene is not expressed in most normal tissues, in contrast with its marked
      expression in proliferating cancer cells. An effective way to explore the gene
      functions of CDC6 is to knock-down the CDC6 messenger RNA (mRNA) and examine the
      phenotypic consequences. In this chapter, we describe the construction of a
      lentivirus vector to express a CDC6 DNA segment. The transcript is able to fold
      by itself because the sense and antisense regions are complementary. There is a 9
      nucleotide (nt) loop region allowing for the short hairpin RNA (shRNA) to form.
      Cellular ribonucleases process the shRNA into a functional short interfering RNA
      (siRNA). Down-regulation of Cdc6 protein is confirmed by Western blots.

PMID- 16957384
TI  - Gene silencing in vitro and in vivo using intronic microRNAs.
AB  - MicroRNAs (miRNAs), small single-stranded regulatory RNAs capable of interfering
      with intracellular messenger RNAs (mRNAs) that contain either complete or partial
      complementarity, are useful for the design of new therapies against cancer
      polymorphism and viral mutation. Numerous miRNAs have been reported to induce RNA
      interference (RNAi), a posttranscriptional gene-silencing mechanism. Recent
      evidence also indicates that they are involved in the transcriptional regulation
      of genome activities. They were first discovered in Caenorhabditis elegans as
      native RNA fragments that modulate a wide range of genetic regulatory pathways
      during embryonic development, and are now recognized as small gene silencers
      transcribed from the noncoding regions of a genome. In humans, nearly 97% of the
      genome is noncoding DNA, which varies from one individual to another, and changes
      in these sequences are frequently noted to manifest clinical and circumstantial
      malfunction. Type 2 myotonic dystrophy and fragile X syndrome were found to be
      associated with miRNAs derived from introns. Intronic miRNA is a new class of
      miRNAs derived from the processing of nonproteincoding regions of gene
      transcripts. The intronic miRNAs differ uniquely from previously described
      intergenic miRNAs in the requirement of RNA polymerase (Pol)-II and spliceosomal
      components for its biogenesis. Several kinds of intronic miRNAs have been
      identified in C. elegans, mouse, and human cells; however, neither function nor
      application has been reported. Here, we show for the first time that intron
      derived miRNA is not only able to induce RNAi in mammalian cells but also in
      fish, chicken embryos, and adult mice, demonstrating the evolutionary
      preservation of this gene regulation system in vivo. These miRNA-mediated animal
      models provide artificial means to reproduce the mechanisms of miRNA-induced
      disease in vivo and will shed further light on miRNA-related therapies.

PMID- 16957385
TI  - Isolation and identification of gene-specific microRNAs.
AB  - Prediction of microRNA (miRNA) candidates using computer programming has
      identified hundreds and hundreds of genomic hairpin sequences, of which, the
      functions remain to be determined. Because direct transfection of hairpin-like
      miRNA precursors (pre)-miRNAs in mammalian cells is not always sufficient to
      trigger effective RNA-induced gene-silencing complex (RISC) assembly, a key step
      for RNA interference (RNAi)-related gene silencing, we developed an intronic
      miRNA-expressing system to overcome this problem, and successfully increased the
      efficiency and effectiveness of miRNA-associated RNAi induction in vitro and in
      vivo. By insertion of a hairpin-like pre-miRNA structure into the intron region
      of a gene, this intronic miRNA biogenesis system has been found to depend on a
      coupled interaction of nascent precursor messenger RNA transcription and intron
      excision within a specific nuclear region proximal to genomic perichromatin
      fibrils. The intronic miRNA was transcribed by RNA type II polymerases,
      coexpressed with a primary gene transcript, and excised out of its encoding gene
      transcript by intracellular RNA splicing and processing mechanisms. Currently,
      some ribonuclease III endonucleases have been found to be involved in the
      processing of spliced introns and probably facilitating the intronic miRNA
      maturation. Using this miRNA-expressing system, we have shown for the first time
      that the intron-derived miRNAs were able to induce strong RNAi effects in not
      only human and mouse cells but also zebrafish, chicken embryos, and adult mice.
      Based on the strand complementarity between the designed miRNA and its target
      gene sequence, we have also developed a miRNA isolation protocol to purify and
      identify the mature miRNAs generated by the intronic miRNA-expressing system.
      Several intronic miRNA identities and structures are currently confirmed to be
      active in vitro and in vivo. According to this proof- of-principle method, we now
      have the knowledge to design pre-miRNA inserts that are more efficient and
      effective for the intronic miRNA-expressing system.

PMID- 16957386
TI  - Transgene-like animal models using intronic microRNAs.
AB  - Transgenic animal models are valuable tools for testing gene functions and drug
      mechanisms in vivo. They are also the best similitude of a human body for
      etiological and pathological research of diseases. All pharmaceutically developed
      drugs must be proven safe and effective in animals before approval by the Food
      and Drug Administration to be used in clinical trials. To this end, the
      transgenic animal models of human diseases serve as a front line for drug
      evaluation. However, there is currently no transgenic animal model for microRNA
      (miRNA) research. miRNAs, small single-stranded regulatory RNAs capable of
      silencing intracellular gene transcripts that contain either complete or partial
      complementarity to the miRNAs, are useful for the design and development of new
      therapies against cancer polymorphism and viral mutation. Recently, varieties of
      natural miRNAs have been found to be derived from hairpin-like RNA precursors in
      almost all eukaryotes, including yeast (Schizosaccharomyces pombe), plant
      (Arabidopsis), nematode (Caenorhabditis elegans), fly (Drosophila melanogaster),
      fish, mouse, and human, involving intracellular defense against viral infections
      and regulation of certain gene expressions during development. To facilitate the
      miRNA research in vivo, we have developed a state-of-the-art transgenic strategy
      for silencing specific genes in zebrafish, chicken, and mouse, using intronic
      miRNAs. By insertion of a hairpin-like pre-miRNA structure into the intron region
      of a gene, we have found that mature miRNAs were successfully transcribed by RNA
      polymerase (Pol)-II, coexpressed with the encoding gene transcript, and excised
      out of the encoding gene transcript by natural RNA splicing and processing
      mechanisms. In conjunction with retroviral transfection systems, the hairpin-like
      pre-miRNA construct was further inserted into the intron of a cellular gene for
      tissue-specific expression regulated by the gene promoter. Because the retroviral
      vectors were randomly integrated into the genome of its host cell, the most
      effective transgenic animal can be selected and propagated to be a stable
      transgenic line for future research. Here, we have shown for the first time that
      transgene-like animal models were generated using the intronic miRNA-expressing
      system described previously, which has been proven to be useful for both miRNA
      research and in vivo evaluation of miRNA-associated target genes.

PMID- 16957387
TI  - Evolution of microRNAs.
AB  - MicroRNAs (miRNAs) form a large class of small regulatory RNAs in eukaryotes.
      Although they share a common processing pathway and certain structural features,
      in general, there is no detectable sequence similarity among miRNAs from a given
      organism. On the other hand, many miRNAs are members of a family of a few, often
      very similar, paralogs. It is, thus, of interest to trace the evolutionary
      history of individual miRNAs, to identify the timing of gene duplications, and to
      study relationships between the histories of different miRNA families. Some
      miRNAs are transcribed from polycistronic primary transcripts. In these cases, we
      will study the evolution of entire clusters.

PMID- 16957388
TI  - MicroRNA protocols. Perspectives.
AB  - The discoveries of microRNAs (miRNAs), a class of noncoding RNAs that can
      regulate gene expression by translational repression, have opened a new avenue on
      gene modulation in mammalian cells. Conceivably, this highly effective method of
      modulation of gene expression would be exploited for numerous prospectives,
      including human, therapeutics. This chapter offers some perspective, with
      emphasis on areas that can be further developed.

PMID- 16957389
TI  - [Ecophysiological mechanism underlying the impacts of nitrogen saturation in
      terrestrial ecosystems on plants].
AB  - Human activities such as combustion of fossil fuels, production and application
      of nitrogen fertilizer, and intensive agriculture and stockbreeding, have
      significantly elevated the reactive nitrogen concentration in the atmosphere,
      leading to nitrogen accumulation, and even nitrogen saturation in some
      terrestrial ecosystems. The status of global nitrogen deposition and the concept
      of nitrogen saturation are reviewed, and the research progress concerning
      ecophysiological response of the plants to nitrogen saturation, including
      photosynthesis, nutrient absorption and stress resistance, are described and
      discussed in details.

PMID- 16957390
TI  - Differential expression of proteins in rice leaves cultivated with different
      forms of nitrogen nutrients.
AB  - Nitrate as one of the two main nitrogen source compounds, acts also as a potent
      signal substance in plant growth and development. It is increasingly interesting
      to determine whether nitrate itself or the derived metabolites acts as a signal
      during the regulation. Rice seedlings were treated with different nitrogen forms
      (NO(-)(3) vs. NH(+)(4)) and total proteins extracted either from nitrate-fed or
      ammonium-fed leaves were separated by two-dimensional gel electrophoresis (2-DE),
      and then the differentially-expressed proteins were identified by MALDI-TOF-MS or
      ESI-Q-TOF-MS. Twenty-six proteins were up-regulated with NO(-)(3) as the nitrogen
      source while 6 were up-regulated with NH(+)(4) as the nitrogen source. MS
      analysis, in combination with database searching, allowed for only a total of 11
      proteins identified with significant probability. Among them 7 nitrate-up
      regulated proteins were identified, i.e., a PSII oxygen-evolving complex protein
      1 (N1), a putative CC-NBS-LRR resistance protein MLA13 (N2), a 23-kD polypeptide
      of PSII (N3), a translation initiation factor eIF-5A (N5), a putative PSII oxygen
      evolving complex protein 2 precursor (N8), an unknown protein (N17), and the
      ubiquitin carrier protein UBC7 (N18). Four ammonium-up-regulated proteins were
      identified as the ATP synthase beta subunit (A1), the putative aminotransferase
      (A3), a hypothetical protein (A5), and OSJNBb0032K15.22 (A6). These results give
      some new insights into both the biochemical adaptation of plant to different
      nitrogen forms (NO(-)(3)/NH(+)(4)) and the differences in responses signaled by
      NO(-)(3)/NH(+)(4) in rice.

PMID- 16957391
TI  - Cloning and expression analysis of beta-galactosidase gene related to softening
      of banana (Musa sp.) fruit.
AB  - Beta-galactosidase is thought to be involved in fruit softening through cleaving
      beta(1-->4) galactan bonds in cell wall hemicellulose. To study the relationship
      between fruit softening and beta-Gal during banana (Musa sp.) fruit ripening, a
      beta-Gal cDNA fragment, named MA-Gal, has been cloned from banana fruit pulp
      using RT-PCR in this study. The results of sequence analysis showed that MA-Gal
      contained 927 bp, encoding a polypeptide of 309 amino acids, the deduced protein
      was highly homologous to plant beta-galactosidase expressed in fruit ripening.
      The MA-Gal putative amino acids have five homologous domains (typical eukaryotic
      beta-Gals have seven domains), contain the GGPIILSQIENEY(F) motif, which is a
      presumptive catalytic active site conserved in all beta-Gals. Phylogenetic
      analysis showed that MA-Gal was in plant beta-Gal group I, which was expressed in
      fruit tissue. The changes in beta-Gal activity and firmness in pulp during three
      different stages were also assayed. The Northern analysis showed that the MA-Gal
      transcripts in pulp were detected at low level at preclimacteric stage, while an
      increasing progression was observed during fruit ripening, and the highest
      transcript amount was found at the postclimacteric stage. These results suggest
      that MA-Gal may play a role during banana fruit ripening and softening.

PMID- 16957392
TI  - [The morphological structure of salt gland and salt secretion in Aeluropus
      littoralis var. sinensis Debeaux].
AB  - The leaves of Aeluropus littoralis var. sinensis Debeaux were scanned with a
      scanning electron microscope, it showed that the upper-epidermis had almost the
      same number of salt glands as the lower-epidermis (Plate I-1, 2), and the salt
      gland is the typical bicelluar gland, which consists of a large basal cell inlaid
      into the epidermis and a small cap cell (Plate I-6). These salt glands were
      distributed mainly on the leaf veins, which favors the rapid collection of salts
      from the roots. Ion X-ray microanalysis indicated that the salt glands could
      effectively absorb Na(+) from the epidermal cells and mesophyllous cells (Table
      1), then secreted Na(+) from the cap cells (Plate I-4), which would decrease the
      salinity of plant. After the plants were treated with various salts for 17 d, the
      ion contents of the leaves and the secretion were measured, and the results
      implied that salt glands had different selection in absorbing and secreting Na(+)
      , K(+) and Ca(2+), that is, the plants first selected K(+) when absorbing ions,
      while first selected Na(+) when sending ions out, but Ca(2+) was fewer in both
      absorbed and secreted, and the order of secretion of the three ions was found to
      be Na(+)>K(+)>Ca(2+) (Figs. 1-6). The secretion of Na(+) or three ions were
      respectively higher than that of leaves within 24 h (Figs. 1, 2, 7, 8), while
      K(+) situation was completely opposite with them (Figs. 3, 4). At the same time,
      the total ion content and composition inside the leaves remained more or less
      constant (Fig. 8).

PMID- 16957393
TI  - [Overexpression of small heat-shock protein of endoplasmic reticulum enhances
      resistance of tomato to tunicamycin].
AB  - The accumulation of unfolded proteins in the endoplasmic reticulum (ER) lumen
      causes ER stress response in eukaryote cells, activates the unfolded protein
      response (UPR) and consequently induces the expression of ER-located molecular
      chaperones (such as BiP, calnexin, etc.). In this study, the full-length small
      heat-shock protein of endoplasmic reticulum cDNA (ER-sHSP) under the control of
      CaMV 35S promoter was introduced into tomato by Agrobacterium tumefactions
      mediated method (Fig. 1, Table 1). Overexpression of ER-sHSP enhanced the
      resistance of the transgenic plant to tunicamycin (Fig. 2, Table 2), an inducer
      of ER stress. Tunicamycin treatment induced an increase in mRNA level of BiP and
      calnexin in plant cell, but mRNAs of these two genes in transgenic plants were
      accumulated to a much smaller extent than those in non-transgenic plants (Fig.
      3). These results indicated that ER-sHSP could alleviate the ER stress and may be
      involved in the UPR signal transmission pathway.

PMID- 16957394
TI  - [Genetic mapping of rice gene OsALB23 regulating chloroplast development].
AB  - The biogenesis of chloroplast from proplastid is the prerequisite of
      photosynthesis. Using electron microscope, we found that rice albino mutant
      Osalb23 had no thylakoid inside the chloroplast, only some empty vesicles could
      be observed (Fig. 2). Genetics analysis showed that albino phenotype was
      controlled by a single recessive locus. Using map-based cloning technique,
      OsALB23 has been mapped to a region of 280 kb between molecular markers R2M501
      and R2M502 on chromosome 2 (Fig. 4). Homologous analysis indicated that this
      region contained six chloroplast protein genes.

PMID- 16957395
TI  - [Carbohydrate metabolism during fruit development of bayberry (Myrica rubra Sieb.
      et Zucc.)].
AB  - The dynamics of dry and fresh weight, the glucose, fructose, sucrose, titratable
      acid contents, and activities of sucrose-metabolizing and hexose-metabolizing
      enzymes were examined in developing fruits of bayberry (Myrica rubra Sieb. et
      Zucc. cvs. 'Wuzi' and 'Biqi'). The results showed the dry and fresh weight of
      bayberry fruit increased with fruit development and maturation (Fig. 1), with the
      highest increase rate of dry matters and water occurring during later stage of
      fruit development (about 10 d before maturation). The change in titratable acid
      followed a course of "low-high-low" in developing bayberry fruits (Fig. 3). The
      titratable acid content reached its peak at about 18 d before fruit maturation,
      and then decreased rapidly. The sugar compositions in fruits of bayberry cv.
      'Wuzi' were different from those in fruits of bayberry cv. 'Biqi'. The main sugar
      accumulated in fruits of bayberry cv. 'Wuzi' was sucrose, accounting for 2/3 of
      total sugars but the sucrose content in fruits of bayberry cv. 'Biqi' was below
      50% of total sugars. The fructose content in fruits of bayberry cv. 'Wuzi' was 4%
      higher, but that in fruits of bayberry cv. 'Biqi' was 12% lower than glucose
      content (Fig. 2). The activities of sucrose cleavage enzymes (invertase and
      cleavage activity of SS) in the fruit of bayberry cv. 'Biqi' increased with fruit
      development and maturation, but those activities in fruit bayberry cv. 'Wuzi'
      were almost stable during fruit development with lower levels of enzyme
      activities in fruit of cv. 'Wuzi' than in cv. 'Biqi' throughout fruit development
      (Fig. 4 and Fig. 5A). The SPS activity increased during fruit development (Fig.
      6), however, the activity peak of synthetic activity of SS occurred at the middle
      stage of fruit development (Fig. 5B). The FRK activity in fruit of bayberry cv.
      'Wuzi' was higher than that of HXK, but the reverse was in fruit of bayberry cv.
      'Biqi' (Fig. 7). These results suggested that the 2-3 weeks before fruit
      maturation was a key phase for the bayberry development and the formation of
      fruit quality. There was a correlation between water transport and dry matter
      accumulation. The different sucrose constitutions between two varieties may be
      attributed to the differences in the activity levels of the sucrose cleavage
      enzymes while the difference in the ratio of glucose content to fructose content
      may be caused by the different activity levels of the hexose-metabolizing
      enzymes.

PMID- 16957396
TI  - [Purification and characterization of two chitin-binding proteins with lysozyme
      activity from roots of Raphanus sativus].
AB  - A group of chitin-binding proteins were isolated from tuberous roots of Raphanus
      sativus by affinity chromatography with deaminated regenerated chitin (Fig. 1).
      SDS-PAGE showed that there are at least five proteins in the sample (Fig. 2-b).
      Through carboxyl methyl-cellulose chromatography, two chitin-binding proteins
      with lysozyme activity, named as CBP1 and CBP2 (Fig. 3), were purified to
      homogeneity with the molecular weights of 26.9 kD and 24.8 kD respectively (Fig.
      2-d, e). CBP1 and CBP2 were found to be bifunctional enzymes with activities of
      lysozyme and chitinase (Figs. 4, 5), but without chitosanase activity (Table 1).
      The CBP1 and CBP2 could be specifically absorbed by various forms of chitin, such
      as powdered, regenerated and colloidal forms chitin (Fig. 6). No disulfide bridge
      was observed in CBP1 and CBP2 by reduced/nonreduced one-dimensional SDS-PAGE
      (Fig. 7).

PMID- 16957397
TI  - [Drought tolerance of transgenic sweet potato expressing both Cu/Zn superoxide
      dismutase and ascorbate peroxidase].
AB  - Two strains, Cu/Zn SOD and APX gene transferred sweet potato (TS) and non
      transgenic sweet potato (Ipomoea batatas L.) (NT), were used as experimental
      materials to study the drought tolerance under three different degrees of water
      stress: 0, -0.44 MPa, -0.78 MPa. The results showed that activities of Cu/Zn SOD
      and APX increased under -0.44 MPa and decreased under -0.78 MPa (Fig. 2), P(n),
      G(s) and leaf water content decreased, C(i) increased, then decreased under water
      stress (Fig. 6), but under the same PEG concentration all these indexes in the TS
      were higher than those in NT. The accumulation of H(2)O(2) and O(-*)(2) (Fig. 1)
      increased the degree of lipid peroxidation of the plasma membrane (Fig. 4),
      prompted the accumulation of MDA (Fig. 3), and the accumulation of TS always
      lower than the NT at the same PEG concentration. All the results showed that the
      transgenic sweet potato has a stronger ability to clean up active oxygen than the
      non-transgenic one, and it can keep a higher leaf water content and P(n) under
      water stress, so it has a stronger tolerance to drought.

PMID- 16957398
TI  - [Transpositional behaviour analysis of Ds element from different insertion sites
      on chromosome 4 in rice].
AB  - Transgenic plants with Ds element distributed over different loci on chromosome 4
      (Fig. 1) and the homozygous transformants with Ac transposase gene were
      established through Agrobacterium-mediated approach. In this study, the plants
      carrying Ds element from different loci were crossed with the plant carrying Ac
      transposase individually. The plants of F(1) generation carrying both Ds element
      and Ac transposase were used to produce the F(2) populations (Table 1). Analysis
      of the F(2) generation by the PCR method revealed that the excision frequencies
      of Ds element were higher in the telomeric region of chromosome 4 than in the
      centromeric region (Fig. 4). These results showed that the insertion site of Ds
      element has strong effect on its excision frequency. We suggest that the special
      construct of chromosome near the insertion site of Ds element is related to the
      excision frequency of the Ds element.

PMID- 16957399
TI  - [Glycinebetaine applied through roots protects the photosynthetic apparatus of
      tobacco seedlings under water stress].
AB  - Two tobacco (Nicotiana tabacum L.) cultivars (DHJ5210 and ZY100) with different
      drought tolerance were used to study the photosynthetic response to different
      water stress and the effects of glycinebetaine applied through roots on
      photosynthetic capacity. The physiological mechanisms of the improvement of
      tobacco photosynthesis by glycinebetaine applied through roots were analyzed. The
      results indicated that photosynthetic apparatus of tobacco leaves were more
      brittle and damaged by water stress, accompanied by negative changes of RWC (Fig.
      2), chlorophyll content (Fig. 3), PSII photochemistry efficiency (Fig. 4),
      activity of Hill reaction (Fig. 5) and ATPase (Fig. 6), and the damage was more
      serious to ZY100 (drought sensitive cultivar) than DHJ5210 (drought resistant
      cultivar) under the same stress condition. Glycinebetaine applied through roots
      could be absorbed by tobacco roots and then accumulated in leaves (Fig. 1), which
      alleviated the decrease in photosynthetic variables of two cultivars and the
      improvement was more significant on ZY100 than DHJ5210. The positive function of
      glycinebetaine might be involved in its protective effect on antioxidant enzymes
      (Fig. 8), chloroplast protein and thylakoid membrane (Fig. 7).

PMID- 16957400
TI  - [Photosynthetic acclimation to elevated CO2 in strawberry leaves grown at
      different levels of nitrogen nutrition].
AB  - Photosynthetic characteristics of strawberry (Fragaria ananassa Duch cv.
      'Toyonoka') leaves grown in either elevated CO(2) (700 microL/L) or ambient CO(2)
      (390 microL/L), and at three levels of nitrogen nutrition (12 mmol/L, 4 mmol/L,
      0.4 mmol/L) were studied. The results showed that for strawberry grown in 12
      mmol/L nitrogen, P(n), maximal carboxylation rate (V(c, max)), maximal linear
      electron flow through photosystem II (J(max)), electron flow to the
      photosynthetic carbon reduction cycle (J(c)) and q(P) were all significantly
      higher in plants grown and measured at elevated CO(2) than for plants grown and
      measured at ambient CO(2) (Table 1 and 2, Fig. 2), which were due to a
      significant increase in J(c) exceeding any suppression of electron flow to the
      photorespiratory carbon oxidation cycle (J(o)). This increase in
      photochemistrical quenching with decreased non-photochemistrical quenching (q(N)
      or NPQ) at elevated CO(2) alleviated photoinhibition by high light (Table 2, Fig.
      3). For plants grown at 4 mmol/L and 0.4 mmol/L nitrogen, P(n), V(c, max), J(c)
      and q(P) were all significantly lower in plants grown and measured at elevated
      CO(2) than for plants grown and measured at ambient CO(2) (Table 1 and 2, Fig.
      2). Consistent with decreased photochemistrical quenching and increased non
      photochemistrical quenching (q(N) or NPQ), for leaves grown at 4 mmol/L and 0.4
      mmol/L nitrogen, the photoinhibition was aggravated by elevated CO(2) (Table 2,
      Fig. 3). Elevated CO(2) suppressed J(o) in leaves of plants grown at 12 mmol/L, 4
      mmol/L and 0.4 mmol/L nitrogen (Fig. 2). The results above suggested that
      deficient nitrogen (4 mmol/L and 0.4 mmol/L nitrogen) and elevated CO(2) result
      in an acclimatory decrease of photosynthesis in leaves of plant grown in elevated
      CO(2).

PMID- 16957401
TI  - [Observation of binding sites of exogenous calmodulin and its extracellular
      effect in suspension-cultured Arabidopsis cell].
AB  - Peptide signals play very important roles in the process of plant development,
      growth and defense to various stresses. Apoplast calmodulin, putative
      extracellular peptide signal, not only existed in extracellular space, but also
      had biological functions. So it is important to provide evidences for
      extracellular calmodulin binding sites and mechanism of signaling. In this paper,
      exogenous FITC-ACaM2 was observed only in the outside of cell using Laser
      scanning confocal microscope (Fig. 2), and (35)S-ACaM2 binding to suspension
      cultured Arabidopsis cells at 25 degrees C was equal to that at 4 degrees C (Fig.
      3), provided direct evidences that exogenous calmodulin was not endocytosed into
      cytoplasm. SDS-PAGE and radiography showed (35)S-ACaM2 intactly existed in
      extracellular space of suspension-cultured Arabidopsis cells (Fig. 4). Exogenous
      ACaM2 could specifically promote activity of GTPase(Fig. 5) and [Ca(2+)](cyt)
      (Fig. 6). These results indicated exogenous calmodulin could bind to the surface
      sites of the suspension-cultured Arabidopsis cells, and then the extracellular
      signal was transferred into cytoplasm signal by transmembrane signaling to
      regulate the biological functions.

PMID- 16957402
TI  - [Effects of Broad bean wilt virus 2 isolate infection on photosynthetic
      activities and chloroplast ultrastructure in broad bean leaves].
AB  - The effects of Broad bean wilt virus 2 (BBWV 2) isolate B935 and PV131 infection
      on photosynthetic activities and chloroplast ultrastructure in broad bean (Vicia
      faba) were investigated. As the disease progressed, net photosynthetic rate
      (P(n)), stomatal conductance (G(s)) of leaves, the chlorophyll content and
      chlorophyll a/b ratio decreased while the intercellular CO(2) concentration
      (C(i)) of leaves rose in comparison with that of the healthy plants (Figs. 1, 2).
      After BBWV 2 infection, F(v)/F(m), F(v)'/F(m)', Phi(PSII) and q(P) values all
      became lower, but the NPQ values were higher, than the healthy control plants
      (Fig. 3). Electron microscopy showed that BBWV 2 infection disrupted the
      chloroplast structure. Most of the B935-infected chloroplasts showed inhibition
      of lamellar development or membrane vesiculation (Fig. 4B, C) and PV131-infected
      chloroplasts showed swollen or disintegrated membrane (Fig. 4D-F). Chloroplasts
      of PV131-infected leaves were different from those of normal ones to a higher
      degree than those of the B935-infected ones, which suggests that the disruption
      of chloroplast structure by virus invasion is responsible for the suppression of
      photosynthesis, which is more serious with PV131 than with B935.

PMID- 16957403
TI  - Proteomic technique used in studying ovule development of Chinese pine (Pinus
      tabulaeformis Carr.).
AB  - Chinese pine (Pinus tabulaeformis Carr.) is one of the most important
      afforestation and ornamental species in China. Ovule abortion is a serious
      problem influencing the output of seeds and reproduction of Chinese pine. So it
      is of much significance to study the mechanisms of ovule development and abortion
      of Chinese pine. By combining two-dimensional gel electrophoresis (2-DE) and mass
      spectrometry analysis, the patterns of gene expression in a specific tissue at a
      specific stage can be displayed and characterized. This study acquired an
      appropriate protein extraction method from ovules of Chinese pine and optimized
      the conditions for protein identification by mass spectrometry.

PMID- 16957404
TI  - Growth reference charts: which are more appropriate?

PMID- 16957405
TI  - Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr).
AB  - The aim of this study is to extend to pre-school ages the Italian Society for
      Pediatric Endocrinology and Diabetes (SIEDP)-2002 growth charts for height,
      weight and body mass index (BMI), to obtain charts (SIEDP-2006) that apply to the
      Italian population from 2 to 20 yr of age, taken as a whole, or separately in two
      geographical areas (Central-North Italy and South Italy). The charts are based on
      a sample of about 70,000 subjects attending infant, primary and secondary
      schools, between 1994 and 2004. The distribution of the sample by gender, age and
      geographic area was roughly similar to that of Italian school population in the
      last decade of the 20th century. Height and weight were measured using portable
      Harpenden stadiometers and properly calibrated scales, respectively. SIEDP-2006
      references are presented both as centiles and as LMS curves for the calculation
      of SD scores, and include the extra-centiles for overweight and obesity. Large
      differences in BMI growth pattern emerged between the SIEDP-2006, 2000 CDC and
      UK90 references: in Italy, BMI is higher and its distribution is more skewed
      during childhood and adolescence. At the end of growth, median values of the
      three references are similar, but the 97th centile of 2000 CDC charts is much
      higher and increases more steeply than that of SIEDP-2006 charts, which on the
      contrary reach a plateau. SIEDP-2006 references intend to supply pediatricians
      with a tool that avoids the use of charts that are outdated or that refer to
      other populations, and thus should be suitable for adequately monitoring the
      growth of their patients.

PMID- 16957406
TI  - Effectiveness of radioiodine (131-I) as definitive therapy in patients with
      autoimmune and non-autoimmune hyperthyroidism.
AB  - We evaluated the outcome of radioiodine (RAI) therapy in 100 consecutive patients
      treated in the period 2000-2001 for hyperthyroidism due to Graves' disease (GD),
      toxic adenoma (TA) and toxic multinodular goiter (TMG). Thyroid function was
      measured before and after therapy every 3-6 months up to 3 yr. Three years after
      therapy, 75% of TA patients were euthyroid, 18.7% were hypothyroid and 6.3%
      hyperthyroid. Of the TMG patients, 62.2% were euthyroid, 18.9% were hypothyroid
      and 18.9% hyperthyroid. In GD patients euthyroidism was achieved in 12.9% of the
      patients, hypothyroidism in 74.2% and hyperthyroidism persisted in 12.9%.
      Definitive hypothyroidism was significantly higher in GD (p<0.0001) than in TA
      and TMG patients. Overall, positive effect of RAI (definitive hypothyroidism or
      euthyroidism) was very high: 93.7% in TA, 81.1% in TMG and 87.1% in GD patients.
      Thyroid volume reduction was observed in all patients, but was higher in GD
      patients (mean reduction of 76%) and in TA patients (mean nodule reduction of
      69%). In TMG, mean reduction was of 32%. The median activity of RAI received by
      the 86 cured patients was 555 MBq (15 mCi) compared to 407 Mbq (11 mCi) received
      by the 14 patients who remained hyperthyroid. No influence was found between
      outcome and clinical parameters at the moment of 131-I therapy. In conclusion,
      our results indicate that RAI therapy is highly effective and safe for the
      control of hyperthyroidism.

PMID- 16957407
TI  - Potential role of hypothalamic ghrelin in the pathogenesis of human obesity.
AB  - Ghrelin is a potent appetite stimulator, mainly synthesized in the stomach but
      also made in the brain. Paradoxically, obese subjects have lower plasma ghrelin
      than lean subjects and increase their weight in spite of low ghrelin levels. We
      hypothesize that central, and not peripheral ghrelin, is primarily responsible
      for overeating in humans. The aim of this study was to determine hypothalamic
      ghrelin levels in lean vs obese subjects. We collected anterior hypothalamus from
      lean and obese patients at the time of autopsy, and Western blots and
      semiquantitative RT-PCR for ghrelin and neuropeptide Y (NPY) were carried out.
      Our results showed that ghrelin expression was significantly higher in the
      hypothalamus of obese subjects compared to lean ones. This finding correlates
      with similar increases in NPY in the obese group. Ghrelin and NPY mRNA levels
      followed the same trend and were significantly higher in the hypothalamus in
      obese compared to lean subjects, suggesting a central origin for the increased
      protein content in the obese subjects. In conclusion, obesity in humans is
      associated with elevated central ghrelin. This data questions the significance of
      the role of peripheral ghrelin in the regulation of appetite in humans and
      suggests an important role for central ghrelin in the pathogenesis of obesity in
      humans.

PMID- 16957408
TI  - Resistin levels are normal in hypothyroidism and remain unchanged after
      attainment of euthyroidism: relationship with insulin levels and anthropometric
      parameters.
AB  - The aim of this controlled prospective study was to investigate resistin levels
      in hypothyroidism before and after restoration of euthyroidism and correlate the
      results with body weight (BW), body fat (BF), waist circumference (WC), body mass
      index (BMI) and serum insulin levels. Fifty-three hypothyroid patients with
      Hashimoto's disease (6 males, 47 females) and 30 controls matched for age, BMI
      and BF were investigated. Anthropometric parameters, resistin and insulin levels
      were measured. All patients were started on levothyroxine treatment and 4 to 5
      months after initiation of treatment the investigations were repeated.
      Hypothyroid patients exhibited normal resistin values, which were no different
      from controls (mean+/-SD 7.4+/-4.0 vs 5.1+/-3.5 ng/ml, p=0.063). Normalization of
      circulating thyroid hormone levels produced no significant change in resistin
      levels (7.4+/-4.0 vs 6.8+/-4.2 ng/ml, p=ns) and post-treatment resistin levels
      did not differ from euthyroid controls. Furthermore, no gender difference was
      demonstrated in resistin levels either before (6.4+/-3.7 for males vs 7.6+/-4.1
      ng/ml for females, p=ns) or after therapy (7.9+/-4.3 vs 6.7+/-4.3 ng/ml, for
      males and females respectively, p=ns), nor was there a difference in resistin
      levels in either sex induced by treatment of hypothyroidism (6.4+/-3.7 vs 7.9+/
      4.3 ng/ml for males, p=ns, and 7.6+/-4.1 vs 6.7+/-4.3 ng/ml for females, p=ns).
      However, a small but significant difference in resistin levels was found between
      female patients and female controls (7.6+/-4.1 vs 5.0+/-4.0 ng/ml, p=0.047).
      Insulin levels and homeostasis model assessment insulin resistance (HOMA-IR)
      index did not differ before and after treatment in hypothyroid patients (13.0+/
      10.2 vs 12.6+/-11.8 microU/ml, 22.7+/-1.4 vs 21.8+/-1.3, respectively, p=ns for
      both) or between patients and controls. In conclusion, our results demonstrate
      that resistin levels are normal in hypothyroidism and remain within normal range
      after attainment of euthyroidism. Resistin is not associated with serum insulin
      and HOMA-IR index, as well as BMI, BF, WC and BW.

PMID- 16957409
TI  - Relationship between polymorphisms G395A in promoter and C1818T in exon 4 of the
      KLOTHO gene with glucose metabolism and cardiovascular risk factors in Korean
      women.
AB  - BACKGROUND: Recently, klotho has been proposed as a link between cardiovascular
      diseases and premature aging, but the relationship between KLOTHO genes and
      cardiovascular risk factors, especially glucose metabolism, in humans is unclear.
      OBJECTIVES: We investigate the relationship between polymorphisms G395A in
      promoter and C1818T in exon 4 of the KLOTHO gene with glucose metabolism and
      cardiovascular risk factors in Korean women. MATERIAL AND METHODS: In 251 women
      (mean age 51.3+/-6.9 yr), body mass index (BMI), waist circumference, blood
      pressure, fasting plasma glucose, insulin and lipid profiles were measured. The
      genotyping of polymorphisms G395A in promoter and C1818T in exon 4 of the KLOTHO
      gene was performed by allelic discrimination using a 5' nuclease polymerase chain
      reaction assay. RESULTS: Allele frequencies of G395A polymorphism was 0.829 for
      the G allele and 0.171 for the A allele and allele frequencies of C1818T
      polymorphism were 0.804 for the C allele and 0.196 for the T allele, both of
      which were in compliance with Hardy-Weinberg equilibrium and the two
      polymorphisms were in linkage disequilibrium (D'=0.43, p<0.01). Mean systolic
      blood pressure was significantly higher in A allele carriers of G395A
      polymorphism compared with non-carriers, and the significance was persistent even
      after adjustment for age and BMI. Mean fasting plasma glucose was significantly
      higher in T allele carriers of C1818T polymorphism compared with non-carriers,
      and the significance was persistent even after adjustment for age and BMI.
      Subjects without any minor allele from either single nucleotide polymorphisms
      (SNP) had significantly lower mean values for systolic, diastolic blood pressure
      and fasting plasma glucose levels compared with subjects with both minor allele
      from either SNP. CONCLUSIONS: We observed that KLOTHO G395A polymorphism was
      associated with blood pressure and KLOTHO C1818T polymorphism was associated with
      glucose metabolism in Korean women. Further studies are needed to clarify this
      relationship.

PMID- 16957410
TI  - Fasting and post-prandial glycemia and their correlation with glycated hemoglobin
      in Type 2 diabetes.
AB  - OBJECTIVE: The relative contribution of fasting and post-prandial glucose to
      glycated hemoglobin (HbA1c) is controversial. In the present study, we assessed
      the relationship with HbA1c of fasting and post-prandial glucose measured in a
      more naturalistic setting, through home glucose self-monitoring or with a
      continuous glucose monitoring system (CGM). MATERIALS AND METHODS: A consecutive
      series of 300 patients with Type 2 diabetes were enrolled in the study, provided
      that they performed blood glucose self-monitoring. HbA1c and fasting plasma
      glucose (FPG) were measured at enrolment. RESULTS: Both fasting plasma and
      capillary glucose showed a significant correlation with HbA1c (r=0.66 and 0.61,
      respectively; p<0.001). When home glucose monitoring was considered, both mean
      fasting and post-prandial glucose showed a significant correlation with HbA1c
      (r=0.71 and 0.73, respectively). In patients in the lower tertile of body mass
      index (BMI), HbA1c showed a significant correlation at multivariate analysis with
      post-prandial glucose, but not with fasting glucose. In patients with HbA1c >7%,
      both fasting and post-prandial glucose showed a significant correlation, after
      adjustment for age and BMI, with HbA1c (both p<0.01); conversely, in those with
      HbA1c < or =7%, such a correlation could be observed for fasting (p<0.01), but
      not for post-prandial glucose. CONCLUSION: In conclusion, both fasting and post
      prandial glucose contribute to the determination of HbA1c . Home glucose self
      monitoring appears to provide a more accurate assessment of metabolic control
      than a single plasma glucose measurement in experimental conditions. Fasting
      glucose could provide a greater contribution to HbA1c in patients with lower
      HbA1c, while post-prandial glucose seems to play a major role in leaner Type 2
      diabetic subjects.

PMID- 16957411
TI  - Thyroid function and morphology after a successful kidney transplantation.
AB  - Although thyroid disorders related to the end-stage renal disease (ESRD) are well
      known, there are discordant data on the function and morphology of the thyroid
      gland after renal transplantation (RT). The objective of this cross-sectional,
      case-control study was to investigate the prevalence and risk factors for
      disorders in the thyroid function and morphology after a successful RT. Fifty
      consecutive patients (25 females, 25 males) with fully functioning allograft were
      enrolled. Their age at transplant ranged from 23 to 44 yr (median, 38) and their
      post-RT follow-up lasted 15-86 months (median, 23). One hundred healthy subjects
      matched for sex, age and body mass index (BMI) were included as controls. Serum
      free thyroid hormones, TSH, thyroglobulin, thyroid hormone-binding globulin (TBG)
      and iodine urinary excretion were determined; ultrasonographic exam of the
      thyroid gland was performed in all subjects. Age, gender, time elapsed from RT,
      dialysis duration, kidney function, type of immunosuppression and corticosteroid
      dose were considered as possible influencing factors for the thyroid function.
      Hypothyroidism was found in 6% of patients, "low T3 syndrome" in 52%, while
      another 26% had free T3 (FT3), free T4 (FT4) and TSH in the lowest third of the
      normal range, suggesting inhibition of the whole hypothalamic-pituitary-thyroid
      (HPT) axis. Iodine excretion and prevalence of anti-thyroid antibodies were
      similar in both patients and controls. There was no significant difference in the
      thyroid function according to different immunosuppressive regimens. In patients,
      an ultrasonographic exam revealed a very variable thyroid volume ranging from 7.2
      to 24.8 ml. Solid nodules were detected in 12 (24%) cases and cystic lesions in
      another four (8%); they were proven negative at cytological examination. Dialysis
      duration was longer in patients with thyroid nodules than in those without
      (p<0.05). Inhomogeneous hypoechoic pattern typical for chronic thyroiditis was
      more frequent than its biochemical expression. In conclusion, a high prevalence
      of abnormal thyroid morphology was found in patients after a successful RT, being
      partly related to a previous uremia. Abnormalities in the thyroid function are
      likely an expression of the post-transplant general and immunological conditions.
      Endocrinological follow-up is advisable in patients after RT, in order to
      discriminate thyroid dysfunctions which need specific treatments from those that
      can only be followed-up, avoiding inappropriate treatments of biochemical
      abnormalities.

PMID- 16957412
TI  - Comparison of two low-calorie diets: a prospective study of effectiveness and
      safety.
AB  - OBJECTIVE: To evaluate the cost-effectiveness and safety of two distinct low
      calorie diets (LCD). DESIGN: Prospective controlled study. METHODS: 67 obese
      patients [body mass index (BMI) 40 kg/m2] were included in two study groups.
      Group A: 26 patients followed a 458 kcal diet given in three meals for 1 month.
      Group B: 41 patients followed a 800 kcal diet for 3 months and with outpatient
      control. MEASUREMENTS: Anthropometric, cardiovascular risk and nutritional
      profile changes were evaluated, as well as total direct and indirect costs, and
      the incidence of complications. RESULTS: No significant initial differences were
      observed between the two study groups. Eighty-six point two per cent of the
      patients completed the therapy correctly. After treatment a significant decrease
      was observed in the following variables for both groups, but no differences were
      detected between Groups A and B: mean weight loss (A= 9.28 kg, B= 8.7 kg),
      ponderal loss percentage (A/B= 7.2/6.8%), glycemia (A/B= 18.6/12.1 mg/dl),
      systolic blood pressure (SBP) (A/B= 11.8/6.5 mmHg), diastolic blood pressure
      (DBP) (A/B 5.9/6.8 mmHg), and final insulin-resistance (IR) index (A= 4.4, B=
      4.3). Group A had the highest drop in total cholesterol (37.7 vs 8.1 mg/dl) and
      triglycerides (54.4 vs 2.5 mg/dl). No changes were observed in ureic acid, renal
      function and serum albumin. Thirty-six patients (55.3%) suffered trivial
      complications associated to the VLCD (16.9% gastrointestinal, 20% anxiety), with
      no differences between groups. Group A patients were on sick leave due to
      asthenia, and two patients in this group had serious complications (transient
      ischemic attack and atrial fibrillation). The total cost of Group A treatment was
      3018.9 against 582.6 euros for Group B. CONCLUSIONS: The 3-month 800 kcal/day
      VLCD was more cost-effective and safer than the 1-month 458 kcal/day diet.

PMID- 16957413
TI  - Metastatic calcifications and severe hypercalcemia in a patient with parathyroid
      carcinoma.
AB  - Primary hyperparathyroidism is rarely produced by parathyroid carcinoma. We
      present the case of a 63-yr-old man who was admitted due to recent onset of
      constipation, weakness and progressive lethargy. At physical examination, a left
      cervical mass was palpated. Marked hypercalcemia (serum calcium 25 mg/dl) (6.22
      mmol/l) complicated by renal insuficiency (serum creatinine 4.4 mg/dl) (388
      micromol/l) was found, but both were unresponsive to conventional therapy and
      hemofiltration. Autopsy examination showed a carcinoma of the upper left
      parathyroid gland, multiple foci of metastatic calficications in the vessel walls
      and parenchyma of both lungs and kidneys, and the myocardium, which contributed
      to multi-organ failure and death. In addition to describing the clinical
      presentation, we review the mechanism of metastatic calcifications as well as the
      role of renal function and hyperphosphatemia, and the basis for therapy of
      hypercalcemic crisis.

PMID- 16957414
TI  - Rifampin-induced hypothyroidism.
AB  - Three euthyroid patients with Hashimoto's thyroiditis developed hypothyroidism
      after the administration of rifampin. We studied 67 patients with tuberculosis.
      All of them were treated with rifampin. Of the 67 patients, 42 had negative tests
      for anti-thyroid antibodies (ATA) and 25 had positive tests for ATA. The
      diagnosis of Hashimoto's thyroiditis was made on the basis of positive tests for
      ATA. After the administration of rifampin, TSH levels were not significantly
      altered in all of the former 42 ATA-negative patients and in 22 of the latter 25
      ATA-positives, but TSH levels increased in the other three (Patients 1, 2 and 3)
      of the latter 25 ATA-positives. Three euthyroid Hashimoto's patients (Patients 1,
      2 and 3) developed hypothyroidism after the administration of rifampin. This
      rifampin-induced hypothyroidism resolved in each, once rifampin was discontinued.
      A) Patient 1: a 62-yr-old man with lymphoma had pulmonary tuberculosis. After the
      administration of rifampin, serum TSH increased to 170 mU/l; B) Patient 2: a
      peritoneal-biopsy specimen containing Langhans' giant cells led to a diagnosis of
      tuberculous peritonitis in a 66-yr-old woman with ascites. After the
      administration of rifampin, TSH increased to 12.4 mU/l; C) Patient 3: a 56-yr-old
      woman with a liver abscess and lymphadenopathy underwent lymph-node biopsy that
      showed Mycobacterium tuberculosis with caseating granulomas. After the
      administration of rifampin, TSH increased to 21.3 mU/l. After its administration,
      Patients 1, 2 and 3 developed hypothyroidism, and received T4. When rifampin was
      discontinued, the hypothyroidism resolved. After the course of rifampin-therapy
      had been completed, T4 was discontinued. At-risk patients who receive rifampin
      may become hypothyroid.

PMID- 16957415
TI  - Veralipride-induced acute coronary syndrome unmasking a non-secreting
      pheochromocytoma.
AB  - The administration of veralipride, a centrally acting dopaminergic type 2 (DA2)
      receptor antagonist, can decrease hot flushes and improve bone density in post
      menopausal women (1). Therefore, it entails an alternative to hormone replacement
      therapy (HRT) in women who have contraindications to estrogen (1). We herein
      describe the case of a 52-yr-old lady who presented with an acute coronary
      syndrome shortly after taking veralipride. Based on knowledge that DA2 receptor
      antagonists trigger catecholamine release (2), a pheochromocytoma was suspected
      and thereafter diagnosed and excised. Therefore, this is the first case reporting
      on veralipride unmasking a silent pheochromocytoma.

PMID- 16957416
TI  - Unusual presentation of juvenile granulosa cell tumor of the ovary.
AB  - BACKGROUND: We present a case report of juvenile granulosa cell tumor of the
      ovary (JGCT) with an unusual clinical presentation and hormonal secretion. CASE:
      A 16-yr-old girl had developed spontaneous menarche at the age of 12 yr, but
      after this initial menstrual bleeding she had no further periods for 4 yr. She
      had no clinical signs of virilization. Endocrinological studies detected high
      levels of DHEA, 17 hydroxyprogesterone (17OH-P), insulin and PRL, an exaggerated
      DHEA response after ACTH stimulation, and low FSH and high LH values after GnRH.
      An ultrasound examination revealed an irregular structure and increased diameters
      of her right ovary, due to the presence of a cyst. Because exploratory
      laparoscopy revealed the presence of a right ovarian mass, her right ovary was
      removed. JGCT was diagnosed. Ten days after surgery, menstrual bleeding
      initiated. Endocrinological evaluation after the operation showed that 17OH-P,
      insulin and basal FSH and LH serum values had returned to normal, while DHEA
      levels had decreased to within the upper limit of the normal range. Only PRL
      levels remained unchanged. CONCLUSION: Our patient presented some unusual
      characteristics. She did not have precocious puberty, but secondary amenorrhea.
      Hormonal secretion consisted mainly of androgens, even though clinical signs of
      virilization were not present.

PMID- 16957417
TI  - Paracrine and endocrine roles of insulin-like factor 3.
AB  - Insulin-like factor 3 (INSL3) is expressed in Leydig cells of the testis and
      theca cells of the ovary. This peptide affects testicular descent by acting on
      gubernaculum via its specific receptor leucine-rich repeat-containing G protein
      coupled receptor 8 (LGR8). From initial animal data showing the cryptorchid
      phenotype of Insl3/Lgr8 mutants, an extensive search for mutations in INSL3 and
      LGR8 genes was undertaken in human patients with cryptorchidism, and a frequency
      of mutation of 4-5% has been detected. However, definitive proofs of a causative
      role for some of these mutations are still lacking. More recent data suggest
      additional paracrine (in the testis and ovary) and endocrine actions of INSL3 in
      adults. INSL3 circulates at high concentrations in serum of adult males and its
      production is dependent on the differentiation effect of LH. Therefore, INSL3 is
      increasingly used as a specific marker of Leydig cell differentiation and
      function.

PMID- 16957419
TI  - Aldosterone and thrombosis formation: implications for ischemic and
      atherosclerotic heart disease.

PMID- 16957418
TI  - Pre-clinical evidence and clinical translation of benign prostatic hyperplasia
      treatment by the vitamin D receptor agonist BXL-628 (Elocalcitol).
AB  - The active form of vitamin D, 1,25-dihydroxyvitamin D3, is a secosteroid hormone
      that binds to the vitamin D receptor (VDR), a member of the superfamily of
      nuclear receptors, and exerts a number of diverse biological functions. The
      natural hormone and synthetic VDR agonists are well known for their capacity to
      control calcium and bone metabolism, but they also regulate proliferation and
      differentiation of many cell types, and possess exquisite immunoregulatory
      properties, mostly by targeting dendritic cells (DC) and T cells. These
      properties have been clinically exploited in the treatment of different diseases,
      from secondary hyperparathyroidism to osteoporosis to psoriasis. The VDR is
      expressed by most cell types, including cells of the urogenital system such as
      prostate and bladder cells. In particular, the prostate has been recognized as a
      target organ of VDR agonists and represents an extra-renal synthesis site of 1,25
      dihydroxyvitamin D3, but its capacity to respond to VDR agonists has, so far,
      been probed only for the treatment of prostate cancer. We have taken a different
      approach, and have analysed the capacity of VDR agonists to treat benign
      prostatic hyperplasia (BPH), a complex syndrome characterized by a static
      component related to prostate overgrowth, a dynamic component responsible for
      urinary irritative symptoms, and a possible inflammatory component. Pre-clinical
      data reviewed here demonstrate that VDR agonists, and notably BXL-628
      (Elocalcitol), reduce the static component of BPH by inhibiting the activity of
      intra-prostatic growth factors downstream of the androgen receptor, and the
      dynamic component by targeting bladder cells. These data have led to a proof-of
      concept clinical study that has successfully shown arrest of prostate growth in
      BPH patients treated with BXL-628. Ongoing clinical studies will assess the
      capacity of this VDR agonist to reduce symptoms and ameliorate flow parameters in
      BPH-affected individuals. The pronounced effects of BXL-628 on bladder smooth
      muscle cells and its anti-inflammatory properties indeed anticipate beneficial
      effects also on BPH-related lower urinary tract symptoms.

PMID- 16957420
TI  - MEK1/2 inhibition promotes Taxotere lethality in mammary tumors in vivo.
AB  - Taxol (paclitaxel) and Taxotere (docetaxel) are considered as two of the most
      important anti-cancer chemotherapy drugs. The cytotoxic action of these drugs has
      been linked to their ability to inhibit microtubule depolymerization, causing
      growth arrest and subsequent cell death. Studies by a number of laboratories have
      also linked suppression of MEK1/2 signaling to enhanced Taxol toxicity in vitro
      and in vivo. The present study examined the interactions of the semi-synthetic
      taxane Taxotere with MEK1/2 inhibitors in epithelial tumor cells. In vitro colony
      formation studies demonstrated that Taxotere and the MEK1/2 inhibitor PD184352
      interacted in a sequence dependent fashion to synergistically kill human mammary
      carcinoma cells (MDA-MB-231, MCF7) as well as in other tumor cell types; e.g.
      prostate and renal cell carcinoma. Athymic mice were implanted in the rear flank
      with either MDA-MB-231 or MCF7 cells and tumors permitted to form to a volume of
      approximately 100 mm3 prior to a two day exposure of either Vehicle, PD184352 (25
      mg/kg), Taxotere (15 mg/kg) or the drug combination. Tumor volume was measured
      every other day and tumor growth determined over the following approximately 30
      days. Transient exposure of MDA-MB-231 tumors or MCF7 tumors to PD184352 did not
      significantly alter tumor growth rate or the mean tumor volume in vivo
      approximately 15-30 days after drug administration. Transient Taxotere exposure
      of MDA-MB-231 or to a lesser extent MCF7, tumors modestly reduced the mean tumor
      volume in vivo approximately 15-30 days after drug administration. In contrast,
      combined treatment with PD184352 and Taxotere significantly reduced MDA-MB-231
      and MCF7 tumor growth. The tumor control values for MDA-MB-231 cells and MCF7
      cells were 0.43 and 0.71, respectively. Fractionated irradiation of MDA-MB-231
      tumors during drug exposure or single dose irradiation prior to drug
      administration did not significantly further suppress tumor growth beyond that of
      cells exposed to Taxotere and MEK1/2 inhibitor. Single dose irradiation of tumors
      after drug exposure, however, caused a significant further suppression of tumor
      growth below that caused by drug exposure. These findings were also reflected in
      ex vivo colony formation analyses of isolated tumor cells. Collectively, these
      findings argue that Taxotere and MEK1/2 inhibitors have the potential to suppress
      mammary tumor growth in vivo which is enhanced by sequence-dependent exposure to
      ionizing radiation. Based on the cell lines used in these studies, our findings
      argue that the interaction of Taxotere and PD184352 is independent of p53 status,
      estrogen dependency, caspase 3 levels or oncogenic K-RAS expression.

PMID- 16957421
TI  - Concerns about authorship and bias in scientific publications.

PMID- 16957422
TI  - Expanding the scope of hypertension: are we creating new diseases?

PMID- 16957423
TI  - Influence of sympathetic activity on blood pressure and vascular damage evaluated
      by means of urinary albumin excretion.
AB  - To analyze the influence of sympathetic activity on blood pressure (BP) and its
      effects on urinary albumin excretion (UAE), the authors carried out a cross
      sectional study in their local health coverage area. The following variables were
      monitored in a representative sample of the general population made up of 495
      individuals: anthropometric parameters; blood glucose, creatinine, and lipid
      levels; 24-hour urinary albumin, norepinephrine, and epinephrine excretion; and
      BP of patients with known hypertension and newly discovered BP > or =140/90 mm
      Hg, evaluated by ambulatory monitoring. In the multivariate analysis, only
      gender, systolic BP, and UAE were associated with norepinephrine levels; only
      gender, systolic BP, and body mass index were associated with epinephrine. After
      excluding those patients with chronic kidney disease, the multivariate analysis
      showed a strong association between UAE > or =30 mg/d and elevated norepinephrine
      and epinephrine levels. The authors concluded that in the subject population
      there is an association between elevated adrenergic activity and higher UAE,
      independent of factors such as age and BP.

PMID- 16957424
TI  - Effects of the angiotensin II receptor blockers telmisartan vs valsartan in
      combination with hydrochlorothiazide 25 mg once daily for the treatment of
      hypertension.
AB  - To attain recent goals of blood pressure (BP) control, multiple drug therapy
      combinations are required, including higher doses of thiazide diuretics in
      combination with other classes of antihypertensive drug therapy. Thus, the
      authors evaluated the antihypertensive effects of telmisartan vs valsartan when
      combined with hydrochlorothiazide (HCTZ) 25 mg in a large (N=1066), placebo
      controlled trial in patients with stage 1 or 2 hypertension. The primary end
      points were the changes from baseline in seated diastolic and systolic BP at the
      end of the 8-week treatment period. Safety end points included adverse events,
      changes in laboratory parameters, and pulse rate. Changes from baseline in BP
      following telmisartan-HCTZ (-24.0/-17.6 mm Hg) were significantly greater than
      both placebo (-4.4/-6.8 mm Hg) and valsartan-HCTZ (-21.2/-16.1 mm Hg) (vs
      placebo, P<.001 for systolic and diastolic BP; vs valsartan-HCTZ, P=.004 for
      systolic BP and P=.019 for diastolic BP). The total number of patients with at
      least 1 adverse event reported were similar among the 3 treatment groups
      (placebo, 49%; telmisartan-HCTZ, 43%; and valsartan-HCTZ, 38%). In conclusion,
      telmisartan-HCTZ at doses of 80/25 mg lowered both systolic and diastolic BP to a
      greater extent than valsartan-HCTZ at doses of 160/25 mg. These data support
      using a higher dose of a thiazide diuretic (25 mg) with a long-acting angiotensin
      receptor blocker as a useful strategy for improving hypertension control.

PMID- 16957425
TI  - Effects of monotherapy and combination therapy on blood pressure control and
      target organ damage: a randomized prospective intervention study in a large
      population of hypertensive patients.
AB  - This prospective, randomized trial evaluated the effect of monotherapy and
      different combination therapies on cardiovascular target organ damage and
      metabolic profile in 520 hypertensive patients. Patients were allocated to a
      single agent: carvedilol 25 mg, amlodipine 10 mg, enalapril 20 mg, or losartan 50
      mg (groups C, A, E, and L, respectively). After 2 months (level 2), nonresponders
      received a low-dose thiazide diuretic, and after 4 months (level 3), amlodipine
      (groups E, C, and L) and carvedilol (group A). Twenty-four-hour blood pressure
      was significantly lowered in all treatment groups. Blood pressure control was
      more pronounced in patients receiving two or three drugs. At the end of the
      study, the carotid intima-media thickness decreased in group L (P<.01), left
      ventricular mass index in groups E and L (P<.05 and P<.001, respectively), with a
      concomitant reduction in cholesterol in group L (P<.03). Diastolic function
      improved significantly in group L (P<.05). This study describes the need to
      control blood pressure with two or more drugs in most hypertensive patients and
      illustrates good clinical outcomes, independent of blood pressure lowering, using
      combination therapy with losartan, low-dose thiazide, and amlodipine.

PMID- 16957426
TI  - Ambulatory blood pressure monitoring in secondary arterial hypertension due to
      adrenal diseases.
AB  - The aim of this study was to evaluate ambulatory blood pressure monitoring in
      patients with essential hypertension and hypertension caused by adrenal
      pathology. Sixty-six patients with primary aldosteronism, 37 with
      pheochromocytomas, and 45 with adrenal incidentalomas were included. These
      patients were compared with 152 essential hypertensive patients and 64
      normotensive subjects. Ambulatory blood pressure monitoring evaluated daytime and
      nighttime systolic and diastolic blood pressure and heart rate. The authors found
      that the "nondipper" phenomenon was present in 51.5% of patients with primary
      aldosteronism, 43.2% with pheochromocytomas, 42.2% with incidentalomas, 34.2%
      with hypertension, and 15% of subjects who were normotensive. In 58% of primary
      aldosteronism patients with idiopathic adrenal hyperplasia, there was an absence
      of the physiologic blood pressure nocturnal fall (nondipper), which was
      statistically significant (P<.001) compared with nondipper primary aldosteronism
      patients with adrenocortical adenoma (38%). In conclusion, the prevalence of the
      nondipping pattern was higher in patients with adrenal hypertension compared with
      patients with essential hypertension, suggesting an independent cardiovascular
      risk factor.

PMID- 16957427
TI  - Incidence and predictors of angioedema in elderly hypertensive patients at high
      risk for cardiovascular disease: a report from the Antihypertensive and Lipid
      Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
AB  - Angioedema is a rare, potentially life-threatening condition that has been
      associated with angiotensin-converting enzyme inhibitors since their introduction
      in the 1980s. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart
      Attack Trial (ALLHAT), the largest antihypertensive study conducted to date,
      randomized 42,418 participants to a diuretic (chlorthalidone), a calcium channel
      blocker (amlodipine), an angiotensin-converting enzyme inhibitor (lisinopril), or
      an alpha-blocker (doxazosin). Patients who developed angioedema were compared for
      baseline characteristics and changes in antihypertensive drug administration.
      Fifty-three participants developed angioedema during active follow-up: 55% were
      black, 60% men, and 70% were assigned to lisinopril (including 62% of black
      participants with angioedema), 15% to chlorthalidone, 9% to doxazosin, and 6% to
      amlodipine. Six percent occurred within a day of randomization and 23% within the
      first week. Over half did not have an increase in their assigned (blinded)
      antihypertensive drug before angioedema onset; 3 (6%) had a dose increase within
      a week before onset. One patient died following an angioedema episode. The
      occurrence of angioedema in the angiotensin-converting enzyme inhibitor arm
      corresponds with previously reported angioedema-angiotensin-converting enzyme
      inhibitor associations.

PMID- 16957428
TI  - Blood pressure components in clinical hypertension.
AB  - This review offers a critical evaluation of the remarkable progress in
      antihypertensive therapy since its inception. Despite the introduction of newer,
      more sophisticated drugs, treatment results have remained stable. Problems
      impeding further improvement include limited patient compliance, clinical
      inertia, incomplete adherence to guidelines, and dependence on brachial artery
      cuff pressures for diagnosis, risk assessment, and treatment response. Brachial
      artery systolic and pulse pressures do not reliably represent aortic or carotid
      artery pressures, which are better risk predictors for the heart and brain. Mean
      pressure, which is the same throughout the arterial tree, is directly measurable
      by cuff oscillometry, and might become the best single risk predictor. Available
      drugs have limited ability to decrease the aortic stiffness that is responsible
      for the elevated systolic blood pressure of aging. Therefore, to improve risk
      assessment and therapeutic benefit, we might include mean blood pressure and
      pulse pressure into blood pressure measurements, pursue efforts to measure
      central blood pressure, and search for new drugs to reduce arterial stiffness.

PMID- 16957429
TI  - Therapeutic inertia and the Medicare crisis.

PMID- 16957430
TI  - Can the scabies mite be tamed?

PMID- 16957431
TI  - A medical pearl: the "bag of antibiotics" sign in the diagnosis of cutaneous
      leishmaniasis.

PMID- 16957432
TI  - Cumulative irritancy comparison of topical retinoid and antimicrobial combination
      therapies.
AB  - BACKGROUND: The use of multiple topical drugs for the treatment of acne may cause
      elevated irritation. Therefore, the selection of a combination regimen should
      include a careful consideration of the irritation potential of the individual
      acne medications. OBJECTIVE AND METHODS: To compare the cumulative irritation
      potential of adapalene gel 0.1%, tazarotene cream 0.05%, and tretinoin
      microsphere 0.04% when applied in combination with two benzoyl
      peroxide/clindamycin topical gels in 35 healthy subjects in a 3-week, randomized,
      controlled study. RESULTS: The mean cumulative irritancy index of adapalene
      combinations was significantly lower relative to tretinoin and tazarotene
      regimens (all P<.01). Test areas exposed to tretinoin or tazarotene were also
      more likely to be discontinued for severe irritation than those exposed to
      adapalene. There were no serious adverse events. No significant difference in the
      irritancy potentials of tazarotene and tretinoin combination regimens was
      observed. CONCLUSIONS: Adapalene gel 0.1% has tolerability superior to both
      tazarotene cream 0.05% and tretinoin microsphere 0.04% when used in topical
      combination therapy. In view of the lower irritation potential observed in this
      study, along with its demonstrated efficacy, adapalene gel 0.1% in combination
      with antimicrobial agents may be used as part of an aggressive treatment regimen
      for the management of acne.

PMID- 16957433
TI  - Retapamulin ointment twice daily for 5 days vs oral cephalexin twice daily for 10
      days for empiric treatment of secondarily infected traumatic lesions of the skin.
AB  - INTRODUCTION: Retapamulin is a novel, topical antibacterial of the pleuromutilin
      class in development for the treatment of secondarily infected traumatic lesions
      of the skin. METHODS: The efficacy, safety, and tolerability of topical
      retapamulin ointment, 1% for 5 days twice daily was evaluated in 2 identical,
      randomized, double-blind, double-dummy, multicenter studies vs oral cephalexin,
      500 mg twice daily for 10 days, in 1904 patients with secondarily infected
      traumatic lesions. RESULTS: Clinical success rates were 89.5% in protocol
      adherent patients receiving retapamulin compared with 91.9% for cephalexin
      (treatment difference, -2.5% [95% confidence interval, -5.4% to 0.5%]). In
      patients with Staphylococcus aureus or Streptococcus pyogenes at baseline,
      clinical success was 89.2% (365/409) for retapamulin and 92.6% (63/68) for
      cephalexin. Safety and tolerability were similar between treatments.
      Noncompliance (defined as using or taking <80% of doses) was recorded in 8.0%
      (51/636) of patients taking cephalexin compared with 0.39% (5/1268) of patients
      receiving retapamulin. CONCLUSIONS: Retapamulin offers a novel, effective, and
      convenient topical treatment for secondarily infected traumatic lesions.

PMID- 16957434
TI  - A possible additional diagnostic tool for cutaneous melanoma.
AB  - The rise in incidence of malignant melanoma and the dismal prognosis of late
      detection emphasize the need for early detection and recognition of the disease.
      The well-known ABCD method for detection of melanoma has recently been revised by
      adding an "E" for changes in size, shape, color, crusting, itching, bleeding, and
      erythema. In an observational study, 8 of 14 (57%) melanoma patients exhibited a
      particular reddish hue to the skin adjacent to the melanoma, with no
      distinguishable borders. In another study, vascular endothelial growth factor was
      positive in biopsy specimens from 3 of 6 (50%) patients with erythema and in 4 of
      7 (57%) patients without erythema. Platelet-derived growth factor was positive in
      all 6 (100%) of the patients with erythema and in 4 of the 7 (57%) without
      erythema. This erythema can help alert the clinician to the presence of malignant
      melanoma and serve as a prognostic factor or an indicator of the efficacy of
      treatment.

PMID- 16957435
TI  - Oracea (doxycycline monohydrate).

PMID- 16957436
TI  - Xolegel (ketoconazole, 2%).

PMID- 16957437
TI  - Diagnosis and management of a changing congenital melanocytic nevus.
AB  - A 70-year-old man presented with a birthmark on the right upper arm that had been
      present for as long as he could remember (Figure). His physician had referred him
      for a dermatology consultation because the lesion had become larger and darker
      over the past year. What are the next steps in the evaluation and management of
      this patient? The authors discuss the diagnosis and management of a changing
      congenital melanocytic nevus. The epidemiology and risk of transformation into
      melanoma are reviewed. Techniques of biopsy and indications for follow-up are
      discussed. A brief review of giant congenital melanocytic nevi in the newborn is
      also included.

PMID- 16957438
TI  - Chewing gum is made of latex: are individuals with so-called latex allergy
      allergic to it?

PMID- 16957440
TI  - Primary palmoplantar Kaposi's sarcoma: an unusual presentation.
AB  - A 65-year-old diabetic Saudi Arabian man taking glibenclamide for 9 years
      presented with painful reddish patches and plaques involving the palms and soles
      of 6 months' duration. These lesions started as small faint purple-red macules
      and gradually increased in number and size. The patient did not seek any medical
      advice other than for these painful lesions. His medical history was
      insignificant. On examination, the patient had multiple, discrete, dull red-to
      violaceous and tender patches and plaques of variable sizes on both palms and
      soles (Figure 1 and Figure 2). His mucous membranes, scalp, and nails were
      normal. A systemic clinical examination was unremarkable other than an amputation
      of the distal phalanx of the left index. Result of routine laboratory
      investigations including complete blood cell count, liver and renal function
      tests, and chest x-ray were normal. An HIV test was negative. A punch skin biopsy
      taken from the left palm showed acanthosis and spongiosis in the epidermis. The
      dermis showed a large number of dilated, medium-sized capillaries with scanty
      extravasated red blood cells, marked infiltration of lymphocytes and histiocytes,
      and a few plasma cells (Figure 3 and Figure 4). Immunohistochemistry results were
      positive for CD34 and CD68. Polymerase chain reaction for human herpesvirus 8 was
      also positive. The treatment options, including cryotherapy and intralesional
      chemotherapy, were discussed with the patient but, unfortunately, he did not
      return for follow-up.

PMID- 16957441
TI  - Hailey-Hailey.
AB  - An 18-year-old white man with a "rash" on his forehead, neck, and upper part of
      the back for more than 5 years presented to the dermatology clinic complaining of
      chronic irritation and burning in these locations. He first became aware of the
      problem while playing football when he noticed that areas where his shoulder pads
      and helmet contacted his skin were red and irritated. He was treated by his
      primary care physician for contact dermatitis, and the areas partially responded
      to mild topical corticosteroids and emollients. Symptomatic worsening of the
      lesions, including increasing burning pain and a clear discharge, subsequently
      led to a primary care diagnosis of impetigo, which was treated with oral
      antibiotics. Again, there was partial improvement while taking the antibiotics
      but no resolution, and the areas of involvement continued to expand.
      Exacerbations over the next few years were diagnosed as tinea, psoriasis, and
      seborrheic dermatitis, with the patient reporting temporary and incomplete relief
      following treatment for all of the above diagnoses.

PMID- 16957442
TI  - Improvement of cystic fibrosis during treatment with isotretinoin.
AB  - A 15-year-old boy with a history significant for multiple respiratory infections
      since birth presented for evaluation of acne vulgaris. He was initially
      prescribed doxycycline, topical tretinoin, and topical clindamycin solution, with
      the later addition of a benzoyl peroxide preparation to his regimen. The patient
      returned 6 months later after having been diagnosed with CF (cystic fibrosis) by
      sweat testing and genetic testing. His skin condition had not responded
      adequately to prior therapy, so all acne medications were discontinued. The 84-kg
      patient was started on 80 mg (0.95 mg/kg/d) of isotretinoin (13-cis-retinoic
      acid) daily. The patient's dose was decreased to 40 mg/d 2 weeks later following
      an episode of blood in his stool and epistaxis. At the 1- and 2-month follow-up
      visits, the patient reported improvement in his acne and mentioned that his lung
      secretions seemed reduced. His acne cleared after 4 months of therapy, so the
      isotretinoin was discontinued. The patient and his mother noted that no
      respiratory infections had occurred during the course of therapy. The patient's
      acne relapsed nearly 2 years later, so isotretinoin was restarted at 60 mg/d.
      During the next 7 months while on the drug, he experienced no further episodes of
      epistaxis or bloody stools and his acne had resolved by the end of therapy. The
      patient and his mother again reported fewer bronchopulmonary secretions and no
      infections requiring antibiotics during treatment with isotretinoin. This was
      unusual because he had experienced numerous respiratory infections requiring
      antibiotics during the prior 2 years. Since discontinuing the drug, the patient
      has had intermittent pulmonary infections and exacerbations in the symptomatology
      of his CF.

PMID- 16957443
TI  - Sister Mary Joseph's nodule as a presenting sign of internal malignancy.
AB  - CASE 1: A 64-year-old, otherwise healthy woman was referred to the surgery clinic
      for a presumed umbilical hernia. On physical examination, a cutaneous nodule was
      noted on the umbilical region and the patient was referred to the dermatology
      clinic. The patient was reexamined and an erythematous nodule was observed in the
      umbilicus measuring 2.5 cm in diameter. The patient denied pain, change in bowel
      habits, or weight loss. There were no other abdominal masses, no sign of ascites,
      and no regional lymphadenopathy. A skin biopsy from the nodule showed mucinous
      adenocarcinoma. Immunohistochemical staining was positive for carcinoembryonic
      antigen, and negative for cytokeratin (CK)7 and CK20. These results were
      consistent with a Sister Mary Joseph's nodule and led to the diagnosis of an
      occult colon carcinoma. The patient had no risk factors for colorectal carcinoma.
      The patient underwent surgery in another hospital, and died 3 months after the
      initial diagnosis of Sister Mary Joseph's nodule. CASE 2: A 73-year-old woman was
      referred to the dermatology clinic for evaluation of a painful, ulcerated, 3-cm
      lesion in the umbilicus (Figure 1). She was otherwise asymptomatic. A skin biopsy
      showed neoplastic glandular cells infiltrating among collagen bundles (Figure 2).
      Stainings for mucin and for CK7 were positive, while staining for CK20 was
      negative. An abdominopelvic CT scan demonstrated a 3.5-cm space-occupying lesion
      in the liver. Results of gastroscopy, colonoscopy, chest computed tomographic
      (CT) scan, and mammography were normal. Serum levels of the tumor-associated
      protein CA125 were elevated to 164 units, while those of CA 19-9 and
      carcinoembryonic antigen were within normal range. A gynecologic examination and
      a transvaginal ultrasound were normal. The patient had no personal or family
      history of any malignancy or any risk factors for developing a carcinoma. The
      patient was scheduled for a palliative resection of the umbilical nodule,
      combined with a laparoscopic inspection in search of the undetected primary
      tumor. She refused surgery and was lost to follow-up. She died 4 months after the
      initial diagnosis of umbilical metastasis. CASE 3: A 51-year-old man was aware of
      a silent mass in his umbilicus for 2 years without seeking medical advice.
      Following 2 weeks of increasing pain in this area, he was referred to the
      emergency room for a suspected incarcerated umbilical hernia. Surgery revealed a
      mass attached to the fascia and peritoneal fat. The mass was removed and
      diagnosed as a poorly differentiated adenocarcinoma, staining positively for
      carcinoembryonic antigen, and negatively for CK20, CK7, prostate-specific
      antigen, and prostatic acid phosphatase. Both gastroscopy and colonoscopy failed
      to detect the primary tumor. An abdominopelvic CT scan was normal, but a CT scan
      of the chest disclosed a nodule measuring 2.5 x 1.5 cm in the lower lobe of the
      right lung. On bronchoscopy, it was found to be an invasive adenocarcinoma,
      consistent with a primary tumor of the lung. The patient was a heavy smoker (45
      pack-years). The patient received 4 cycles of combined chemotherapy with
      carboplatine and gemcitabine, with no improvement. A month later, the patient
      complained of abdominal pain. Following demonstration of intra-abdominal spread
      of disease by CT scan, a second line chemotherapy was instituted with paclitaxel.
      A month later the patient's condition deteriorated and he complained of cough,
      sweating, and pain along the right leg. A bone scan revealed bone metastases in
      the right femur and left tibia. Two weeks later he was admitted to the hospital
      with intestinal obstruction and underwent laparotomy. He had massive intra
      abdominal spread of cancer and ascites. Only a palliative colostomy was
      performed. The patient died 3 weeks later, 9 months after the diagnosis of
      adenocarcinoma of the lung. The clinical data on the three patients are
      summarized in Table I.

PMID- 16957444
TI  - Valvular heart disease at elderly age: new vistas.

PMID- 16957446
TI  - Age-related changes in hemodynamics affecting valve performance.
AB  - Degenerative processes result in changes in both the aortic and mitral valves.
      For example, degenerative changes may lead to significant aortic stenosis or
      myxomatous mitral valves. Flows through each valve are determined not only by the
      properties of the valve itself, but also by the properties of proximal and distal
      chambers, which also undergo changes with age and diseases associated with the
      elderly, such as hypertension and coronary artery disease. Assessment of valvular
      performance should consider the effects of atrial-ventricular coupling (for the
      mitral valve) or ventricular-arterial coupling (for the aortic valve). Design of
      therapy or intervention should accordingly consider effects on the system as a
      whole.

PMID- 16957447
TI  - Effects of aging on the diagnostic assessment of valvular heart disease.
AB  - The diagnostic assessment of the severity of valvular heart disease in the older
      population is impacted by the anatomic and physiologic changes that accompany
      normal aging and by the interposition of diseases prevalent in the elderly. In
      this paper, the impact of those changes on the assessment of valvular heart
      disease will be reviewed. Special attention will be paid to the effects of age
      and disease on the measurement of the pressure drop and orifice area.

PMID- 16957448
TI  - Percutaneous treatment of valvular heart disease: catheter-based aortic valve
      replacement and mitral valve repair therapies.
AB  - Until recently, percutaneous catheter therapy for valvular heart disease was
      limited to catheter balloon valvuloplasty for aortic, mitral, or pulmonic
      stenosis. A number of new approaches to percutaneous valve therapy are now
      developing rapidly, including methods for catheter-based valve replacement and
      repair. Stent-mounted valve prostheses have been successfully implanted in the
      pulmonic and aortic positions. These devices have been constructed using
      pericardial valve leaflets mounted inside balloon-expandable or self-expanding
      stents and have been used in patients who are high risk for valve replacement
      surgery. Percutaneous valve repair is also being developed for mitral
      regurgitation. Direct leaflet repair and percutaneous annuloplasty are being
      employed in clinical trials. All the percutaneous approaches are based on
      existing surgical techniques and offer less invasive alternatives. The era of
      percutaneous valve therapy has clearly arrived, and ongoing trials will define
      the clinical role for these new therapies.

PMID- 16957449
TI  - Mitral valve repair in the elderly: the role of the echocardiography/surgery team
      in patient outcome.

PMID- 16957450
TI  - Minimally invasive mitral valve repair with and without robotic technology in the
      elderly.
AB  - An increasing number of elderly persons require mitral valve surgery, primarily
      for mitral regurgitation. Minimally invasive mitral valve repair, including
      robotic surgery, has been shown to be feasible and safe in the general
      population. Minimally invasive cardiac surgery is especially beneficial in the
      elderly because it decreases trauma and speeds recovery. The authors conducted a
      retrospective review of 123 cases of minimally invasive mitral valve repair in
      elderly patients aged 70 years and older and five robotic mitral valve repairs
      using the da Vinci surgical system (Intuitive Surgical, Inc., Sunnyvale, CA) in
      one octogenarian. The authors review their 9 years of experience with minimally
      invasive mitral valve repair in the elderly and compare and contrast other forms
      of surgery in the elderly, including robotic mitral valve repair.

PMID- 16957451
TI  - Age-related structural changes in cardiac valves: implications for tissue
      engineered repairs.
AB  - Elderly patients would receive substantial benefits from tissue-engineered heart
      valves (TEHVs), but most TEHV research has not focused on applications for this
      growing patient population. There will be numerous technical challenges involved
      in developing TEHVs for the elderly, such as designing tissues to accommodate
      higher blood pressure and larger aortic roots that may be friable or calcified.
      Concomitant medications may also affect the biology of the TEHV. Due to the
      predominantly senescent behavior of cells from older persons, a nonautologous
      cell source may be required to develop the TEHV. Decellularized heart valve
      allografts from elderly donors may not be durable enough to use as a scaffold,
      but several polymer and natural biodegradable scaffolds may provide promising
      alternatives. The selection of cell sources, scaffolds, and mechanical/biologic
      conditioning will need to be precisely targeted to meet the diverse
      physiological, medical, and surgical requirements of elderly patients.

PMID- 16957452
TI  - Ethical issue: an oath for our time.

PMID- 16957453
TI  - Abdominal aortic aneurysm in nonagenarians.

PMID- 16957454
TI  - Echocardiographic and electrocardiographic manifestations of heart metastasis
      from primary lung cancer.

PMID- 16957455
TI  - Clopidogrel plus aspirin vs oral anticoagulation for atrial fibrillation: the
      ACTIVE W trial.

PMID- 16957456
TI  - Bradycardia due to blocked atrial bigeminy.

PMID- 16957458
TI  - The relationship between spirituality and compliance in patients with heart
      failure.
AB  - A high incidence of noncompliance to prescribed treatment plans results in
      increased morbidity, hospitalizations, and mortality rates in patients with heart
      failure. Exploration of new avenues to encourage adherence is needed in nursing
      research. The purpose of this study was to explore whether a relationship existed
      between spirituality and compliance in patients with heart failure. The Spiritual
      Assessment Scale and the Heart Failure Compliance Questionnaire Revised were
      mailed to a convenience sample with a return response from 95 participants.
      Although mean scores for the Spiritual Assessment Scale and the Heart Failure
      Compliance Questionnaire Revised were high, data suggested no correlation existed
      between levels of spirituality and degree of compliance among the heart failure
      participants, r=16393; p=0.115. Although insignificant results were found between
      levels of spirituality and degree of compliance, the data did not rule out the
      importance of spirituality as a coping tool.

PMID- 16957459
TI  - Satisfaction with heart transplantation.
AB  - This research investigated patient satisfaction with heart transplantation (HT) 6
      months after surgery. The authors explored whether HT patients would make the
      decision to have HT again and examined medical, psychosocial, and demographic
      factors associated with satisfaction or dissatisfaction in 257 HT recipients.
      Nonparametric statistics were used. Satisfaction with HT could be rated from 1
      (not satisfied) to 10 (very satisfied). Eighty-seven percent of the patients were
      highly satisfied with HT 6 months after surgery (ratings of 8-10); 1% rated their
      satisfaction as low (1-3), and 12% rated it as moderate (4-7). Factors associated
      with less satisfaction with HT were: more symptom distress, greater disability,
      more stress, poor coping ability, feeling that the interventions of the HT team
      were not very helpful, less life satisfaction, and lower quality of life. Ninety
      three percent indicated that they either definitely or probably would decide to
      have HT again; 7% responded "probably not" or "not sure." Factors associated with
      a negative perception of having another HT were: poor coping ability, less life
      satisfaction, lower quality of life, being male, and being married.

PMID- 16957460
TI  - How safe is aggressive statin therapy?
AB  - The most recent guidelines of the National Cholesterol Education Program
      recommend more aggressive low-density lipoprotein cholesterol goals: <100 mg/dL
      for patients at moderate or high risk of cardiovascular disease, and <70 mg/dL
      for patients at very high risk. These lower goals are more likely to be achieved
      using the more powerful statins--atorvastatin, rosuvastatin, and simvastatin.
      Although statins are widely used, extensively studied, and known to have an
      excellent safety profile, the perception of many health care providers and
      patients is that safety concerns about the more efficacious statins, especially
      at high doses, limit their use. However, clinical data consistently support the
      view that adverse events are uncommon even when intensive therapy is used to
      reach aggressive low-density lipoprotein cholesterol goals. Overall, the more
      potent statins have similar safety profiles. The benefits of aggressive statin
      treatment in reducing the risk of cardiovascular events appear to far outweigh
      any potential risks of adverse events.

PMID- 16957461
TI  - Exercise and the heart failure patient: aerobic vs strength training--is there a
      need for both?
AB  - Heart failure (HF) is characterized by general muscular weakness, muscle atrophy,
      and exercise intolerance that lead to reductions in functional capacity, ability
      to perform activities of daily living, and health-related quality of life. Until
      recently, exercise programs for patients with HF were centered on aerobic
      exercise training alone. Although many activities of daily living require
      significant muscle strength, the role of strength training for HF patients,
      either alone or in combination with aerobic exercise, has not been well studied.
      There is suggestive evidence that combined strength-aerobic exercise training may
      offer additional benefits in terms of health-related quality of life and
      functional capacity. Strength training can be targeted to reduce muscle atrophy
      to a greater extent than aerobic training. Further research is required to
      isolate the specific role of strength training regarding improvements in
      prognosis, HF-related morbidity and hospitalization, and health-related quality
      of life for patients with HF.

PMID- 16957462
TI  - End-of-life issues in elderly patients with acute coronary syndrome: the role of
      the cardiovascular nurse.
AB  - End-of-life care and cardiovascular disease are concepts that do not have the
      same synergy as end-of-life care and cancer. Cardiovascular care is predominantly
      perceived by patients and practitioners as a curative discipline. However, with
      the aging of the population and the prevalence of cardiovascular heart disease,
      it will continue to be the leading cause of death for adults in the United
      States. Clinical treatment options and issues surrounding end-of-life care need
      to be addressed with elderly patients and their families. The purpose of this
      article is to discuss the role of the cardiovascular nurse in the care of the
      elderly patient with acute coronary syndrome.

PMID- 16957463
TI  - Premise: digoxin is a drug looking for its place in the museum of medical
      history.

PMID- 16957464
TI  - Use of digoxin in the treatment of chronic heart failure.

PMID- 16957465
TI  - Cardiovascular nursing in Sweden 2006--new challenges for clinical practice,
      education, and research.

PMID- 16957466
TI  - Palliative care for the patient with end-stage heart failure.

PMID- 16957467
TI  - Cardiac monitoring during stress testing.

PMID- 16957469
TI  - Tube feeding decisions in patients with end-stage dementia.

PMID- 16957470
TI  - Duodenal and biliary atresia associated with facial, thyroid and auditory
      apparatus abnormalities: a new mandibulofacial dysostosis syndrome?
AB  - We report a female child born at 36 weeks of gestation with multiple
      abnormalities including dysmorphic and coarse facial features with features of
      mandibulofacial dysostosis that include bilateral microtia with the absence of
      external auditory meati and Mondini dysplasia as well as, duodenal atresia,
      intestinal malrotation, anterior displacement of the anus, left hemiaplasia of
      the thyroid and biliary atresia in sibs. The associations of duodenal atresia
      with intrahepatic and extrahepatic biliary atresia in sibs have been reported,
      suggesting an autosomal recessive syndrome. However, the associated external,
      middle and internal ear anomalies and the thyroid malformation, however, have not
      been reported in this condition. To the best of our knowledge, this is a hitherto
      new syndrome with an unknown inheritance.

PMID- 16957471
TI  - A form of autosomal dominant spondyloepiphyseal dysplasia is caused by a glycine
      to alanine substitution in the COL2A1 gene.
AB  - We report a family with an unusual form of autosomal dominant spondyloepiphyseal
      dysplasia characterized by infantile-onset disproportionate short stature with
      relative shortening of the spine, thoracic kyphosis, lumbar lordosis, scoliosis
      and premature osteoarthritis of the joints especially of the hips. Radiological
      findings include mild platyspondyly, vertebral end plate irregularity, irregular
      femoral necks, and dysplasia of the capital femoral epiphyses with flattening and
      irregularity present from childhood and mild variable epiphyseal dysplasia
      elsewhere in the skeleton. Intrafamilial variability is observed in the degree of
      short stature, severity of spinal and hip involvement and the age of onset of
      symptoms and complications. We demonstrate that this dysplasia is due to a
      glycine to alanine substitution in the COL2A1 gene (p.Gly862Ala), thereby
      expanding the phenotypic spectrum of dysplasias associated with defects in type
      II collagen.

PMID- 16957472
TI  - Concordant familial segregation of atrial septal defect and Axenfeld-Rieger
      anomaly in father and son.
AB  - The association of congenital heart defect and ocular malformations is involved
      in several genetic syndromes, metabolic diseases and environmental entities. We
      report here on father and son, both presenting with the combination of atrial
      septal defect and congenital ocular anomalies in Axenfeld-Rieger anomaly. The son
      had anterior iridotrabecular dysgenesis and posterior embryotoxon bilaterally,
      corneal leucoma and marked iridial vascularization at right. The father had
      bilateral anterior iridotrabecular dysgenesis, posterior embryotoxon and
      nystagmus, and corneal leucoma at left. No additional malformations were noted in
      these patients. The Axenfeld-Rieger syndrome seems to be a spectrum of
      developmental disorders. The present report confirms the existence of a specific
      Axenfeld-Rieger phenotype associated with congenital heart defect. Atrial septal
      defect is the anatomic type of congenital heart defect linked to this condition.

PMID- 16957473
TI  - FGFR1 Pfeiffer syndrome without craniosynostosis: an additional case report.
AB  - Pfeiffer syndrome is an autosomal dominant condition classically encompassing
      both craniosynostosis and digital abnormalities of the hands and feet.
      Individuals with Pfeiffer syndrome may have mutations within either fibroblast
      growth factor receptor 1 gene (FGFR1) or FGFR2. FGFR1 mutations often result in
      less severe craniofacial involvement and hand abnormalities. We report a four
      generation family with an FGFR1 P252R mutation, who have typical hand and feet
      skeletal features of Pfeiffer syndrome without craniofacial involvement. This is
      the third family in the literature in which no family members have craniofacial
      features of Pfeiffer syndrome. The absence of craniosynostosis should not
      preclude the consideration of FGFR mutation analysis in cases in which digital
      features are characteristic of the craniosynostosis syndromes.

PMID- 16957474
TI  - Patient with an EYA1 mutation with features of branchio-oto-renal and oto-facio
      cervical syndrome.

PMID- 16957475
TI  - Oesophageal atresia with a terminal deletion of chromosome 2q37.1.
AB  - We herein report the case of a newborn girl with oesophageal atresia associated
      with cardiac and gastrointestinal anomalies, including patent ductus arteriosus,
      tracheomalacia, and gastro-oesophageal reflux with hiatus hernia. In addition,
      she had a terminal deletion of the long arm of chromosome 2, with a breakpoint of
      2q37.1. The patient died following a cardiac arrest at 90 days of age. No cause
      of death was identified at autopsy.

PMID- 16957476
TI  - Patient with novel interstitial deletion of chromosome 3q13.1q13.3 and agenesis
      of the corpus callosum.
AB  - Interstitial deletions of the proximal long arm of chromosome 3 are rare. Only
      eight previously reported patients have deletions involving the proximal segment
      of 3q. Of these patients, three had agenesis of the corpus callosum and one had
      holoprosencephaly. We report here a patient with a small unique interstitial
      deletion of the long arm of chromosome 3 spanning 3q13.1q13.3. This patient has
      agenesis of the corpus callosum, global developmental delay, and distinctive
      facial features of a small nose, anteverted nares, and broad nasal root. Our
      patient provides further evidence that a gene involved in corpus callosum
      development or neuronal migration may reside in this region.

PMID- 16957477
TI  - Interstitial deletion of the short arm of chromosome 2 in a mother and child,
      with facial dysmorphism and mild learning difficulties.
AB  - We report a mother and son with an interstitial deletion of chromosome 2:
      del(2)(p21p22.2). Both have mildly dysmorphic facial features and learning
      difficulties. This phenotype contrasts with two previously described cases with a
      similar deletion that presented with cyclopia and alobar holoprosencephaly.

PMID- 16957478
TI  - Basilar artery dolichoectasia in a boy with a combination of partial monosomy 18p
      and partial trisomy 20q.
AB  - We describe an 11-year-old boy with facial dysmorphism consisting of a round and
      flat face, hypertelorism, short nose, and down turned corners of the mouth. In
      addition, he had severe mental retardation, short stature, imperforate anus, and
      basilar artery dolichoectasia. Cytogenetic evaluation revealed an unbalanced
      paternally inherited translocation t(18;20)(p11.2q13.3), resulting in partial
      monosomy 18p and partial trisomy 20q. The combination of deletion 18pduplication
      20q has not been previously described and we suggest that the unusual finding of
      basilar artery dolichoectasia may be a feature of one of the imbalances.

PMID- 16957479
TI  - A female with hemihypertrophy and chylous ascites - Klippel-Trenaunay syndrome or
      Proteus syndrome: a diagnostic dilemma.
AB  - Asymmetric overgrowth has many differential diagnoses with considerable overlap,
      posing a diagnostic dilemma. The presence of chylous ascites, though unreported,
      might be expected as a manifestation of overgrowth syndromes with lymphatic
      involvement. We present a patient with hemihypertrophy who presented with chylous
      ascites at birth.

PMID- 16957480
TI  - Handless, footless fetus.
AB  - We report a fetus with symmetrical terminal transverse limb deficiency. Two
      earlier reports described patients with similar defects. These patients resemble
      the animal models that result from the removal of apical ectodermal ridge.

PMID- 16957481
TI  - Symmetrical absence of hands and feet with bilateral radius agenesia: case report
      of a new entity?

PMID- 16957482
TI  - Acro-dermato-ungual-lacrimal-tooth-like syndrome: report of a family with
      variable expression.
AB  - We report the case of a young boy with fine hair, mild nail dysplasia, blocked
      nasolacrimal ducts, absence of central incisors, bilateral oligodactyly of feet
      and anal stenosis. His father showed the same spectrum of anomalies with mild
      expression. He had mild nail dysplasia, blocked nasolacrimal ducts, inferior
      dental cysts with consequent premature tooth loss, frequent dental decays
      consequent to enamel abnormality and cutaneous syndactyly of the second and third
      right toe. The acro-dermato-ungual-lacrimal-tooth syndrome was suspected and
      molecular analysis of the P63 gene was performed, but no mutation was found.
      Although P63 gene analysis was negative, we think that both cases show clinical
      overlap with the acro-dermato-ungual-lacrimal-tooth syndrome and confirm the wide
      expression of this condition, even in the same family.

PMID- 16957483
TI  - Malpuech syndrome: facial features in the absence of clefting.
AB  - We present a girl with Malpuech syndrome. In addition to the typical features of
      intrauterine growth retardation, facial dysmorphism, caudal appendage and patent
      ductus arteriosis, she has an unusual eyebrow pattern with a lateral flare.

PMID- 16957484
TI  - Unusual association of simplified gyral pattern and sparse hair in an Egyptian
      patient with microcephaly-lymphoedema.

PMID- 16957485
TI  - Neuhauser syndrome and Peters' anomaly.
AB  - We report a 9-month-old boy with major features of Neuhauser syndrome, including
      megalocornea, mental motor retardation, hypotonia, dysmorphic findings (high
      arched palate, broad nasal bridge, epicanthus), who also had additional findings
      such as Peters' anomaly, microcephaly, undescended testicle, patent ductus
      arteriosus and atrial septal defects. Ophthalmologic examination demonstrated
      central opacity of the left cornea and lens and iris adhesions extending from the
      pupillary margin to the borders of the opacity. Keratoplasty operation was done
      for the right eye owing to central corneal opacity. Neuhauser syndrome should be
      considered in the differential diagnosis of the patients with megalocornea,
      hypotonia and mental and motor retardation who have dysmorphic findings. To the
      best of our knowledge, Peters' anomaly has not been reported in Neuhauser
      syndrome previously.

PMID- 16957486
TI  - Diencephalic cachexia of infancy: Russell's syndrome.

PMID- 16957487
TI  - Omphalocele in an infant with Cornelia de Lange syndrome.
AB  - Cornelia de Lange syndrome is a genetic condition characterized by a very
      distinctive facial appearance, hirsutism, limb anomalies, growth retardation and
      developmental delay. Most cases occur sporadically as the result of a new
      autosomal dominant mutation, but there are also reports of parent to child
      transmission. Associated clinical features that are less frequent are quite well
      known in this very well described genetic syndrome. Omphalocele does not appear
      to ever have been reported to be an associated feature. We report, for the first
      time, an omphalocele in a molecularly confirmed case of Cornelia de Lange
      syndrome.

PMID- 16957488
TI  - The influence of vagus nerve stimulation on memory.
AB  - BACKGROUND: Vagus nerve stimulation (VNS) has been shown to improve memory.
      OBJECTIVE: The purpose of this study was to learn at which stage of memory
      formation this influence occurs. METHODS: Ten subjects who had been implanted
      with vagus nerve stimulators for the treatment of intractable seizures performed
      tasks that assessed learning and retention (Hopkins Verbal Learning Test) during
      actual and sham VNS. RESULTS: We found that VNS had no effect on learning but
      enhanced consolidation, which led to improved retention. CONCLUSIONS: The means
      by which VNS improves retention is probably related to the increased activity in
      the nucleus of the tractus solitarius and the locus coeruleus-central adrenergic
      system that activates the amygdala and increases long-term potentiation in the
      hippocampus.

PMID- 16957490
TI  - Habituation and dishabituation of P300.
AB  - OBJECTIVE: We aimed to see the consequences of habituation and posthabituation by
      means of repeatedly measuring the effects over a longer period. METHOD: The study
      was performed on 27 healthy volunteers. The event-related potentials were
      recorded from the Fz, the Cz, and the Pz electrode sites. The rare tone-frequent
      tone probability ratio was 20%. All subjects were asked to press a button when
      they heard a rare tone. The test was continued until 20 artifact-free rare tones
      were averaged, which was accepted as 1 trial block. After 10 trial blocks were
      obtained in a sequential manner, the test was completed. RESULT: This study has
      indicated that P300 amplitudes decrease with repeated stimulations, that is,
      there is a habituation period. As the test continues, the speed of amplitude
      decrease slows down and after a while it even starts to increase: that is, a
      dishabituation occurs. CONCLUSIONS: It is very likely that this habituation
      relates to a period of learning and dishabituation relates to a period of mental
      fatigue. In these processes, changes of amplitude and latency values reflect
      changes in amount of neuronal activation.

PMID- 16957489
TI  - Verbal fluency predicts mortality in Alzheimer disease.
AB  - OBJECTIVES: To assess the predictive value of neuropsychologic profiles, at
      diagnosis, for mortality in incident Alzheimer disease (AD). BACKGROUND: Rate of
      AD progression varies significantly across individuals for reasons that are not
      well understood. Several studies have linked rapid decline with
      disproportionately impaired executive functioning, presumably reflecting greater
      impairment of frontal networks. To the extent that differential neuropsychologic
      profiles reflect various neuropathologic presentations of AD, such profiles may
      inform survival estimates early in the disease. METHODS: Five neuropsychologic
      indices were used to characterize performance in 161 individuals at diagnosis of
      AD during a 15-year, longitudinal, primarily community-based study. RESULTS:
      Fifty-two percent of participants reached the mortality end point with a median
      survival of 5.52 years (95% confidence interval, 4.41-6.63). Cox proportional
      hazards analyses indicated that older age at diagnosis was associated with higher
      risk of mortality (risk ratios, 1.08; 95% confidence interval, 1.04-1.12) whereas
      Hispanic ethnicity predicted lower mortality [0.22 (0.09-0.55)]. Controlling for
      these 2 demographic variables, higher verbal fluency scores at diagnosis
      predicted lower mortality [0.69 (0.49-0.96)]. CONCLUSIONS: Disproportionate
      impairment of both category and letter fluency at the earliest stages of AD
      predicts mortality. The prognostic value of these tests may derive from their
      general psychometric properties, or may reflect the measures' sensitivity to an
      early or critical level of compromise to frontal networks.

PMID- 16957491
TI  - Volition and imagery in neurorehabilitation.
AB  - New interventional approaches have been proposed in the last few years to treat
      the motor deficits resulting from brain lesions. Training protocols represent the
      gold-standard of these approaches. However, the degree of motor recovery
      experienced by most patients remains incomplete. It would be important to improve
      our understanding of the mechanisms underlying functional recovery. This chapter
      examines the role of two possible mechanisms that could operate to improve motor
      function in this setting: volition and motor imagery. It is argued that both
      represent possible strategies to enhance training effects.

PMID- 16957492
TI  - Do phonologic and rapid automatized naming deficits differentially affect
      dyslexic children with and without a history of language delay? A study of
      Italian dyslexic children.
AB  - OBJECTIVE: The study aims to verify whether phonologic and rapid automatized
      naming (RAN) deficits are present and associated in Italian dyslexic children and
      whether they differentially affect dyslexics with and without a history of
      previous language delay (LD). BACKGROUND: According to the phonologic core
      deficit hypothesis, dyslexia may stem from impairment of the representation and
      manipulation of phonemes and may be closely associated with oral language
      deficits. However, deficits in tasks not requiring fine-grained phonologic
      representations, such as RAN, have also been described in dyslexic children.
      METHODS: Thirty-seven children were selected on the basis of a reading deficit
      and were assigned to 2 groups according to whether or not they had a history of
      early LD as determined retrospectively by parental report. A battery of reading
      and writing, verbal working memory, metaphonologic, RAN, and visual search tests
      were administered. RESULTS: RAN deficits were shared by most dyslexics (with and
      without a history of LD), whereas phonologic deficits were mainly associated with
      a previous LD. This last condition did not result in a more profound impairment
      of reading and writing decoding skills. CONCLUSION: In a shallow orthography such
      as Italian, RAN, not phonologic deficits, may represent the main cognitive marker
      of developmental dyslexia.

PMID- 16957493
TI  - Attention and memory deficits in schizophrenia: the role of symptoms of
      depression.
AB  - BACKGROUND: Schizophrenic patients suffer from neuropsychologic impairments in
      several cognitive domains, that is, attention and memory. Similar impairments
      have been observed in patients with depression. Therefore, the question arises
      whether and how the symptoms of depression seen in many patients with
      schizophrenia are linked to their neuropsychologic functioning. METHODS:
      Seventeen schizophrenic in-patients (after attenuation of acute psychosis) and 17
      healthy control subjects matched for sex, age, and education were investigated by
      use of an neuropsychologic test battery targeting at attention and memory.
      Symptoms of depression were evaluated by use of 3 self-rating scales and the
      Hamilton Depression Rating Scale. RESULTS: Patients performed significantly worse
      in all neuropsychologic tests applied, except in digit span. Additionally,
      patients exhibited significantly higher levels of depression according to all 3
      self-rating scales and moderate depression severity according to the Hamilton
      Depression Rating Scale (mean: 13.1). By taking the proportion of variance
      explained by the self-ratings of depression statistically into account,
      significant group differences disappeared in half of the attention measures and
      in all memory measures. CONCLUSIONS: These results suggest that part of the
      neuropsychologic impairments seen in schizophrenia is linked with symptoms of
      depression. This seems to be especially true for attention and memory
      disturbances.

PMID- 16957494
TI  - Apparent transient effects of recent "ecstasy" use on cognitive performance and
      extrapyramidal signs in human subjects.
AB  - OBJECTIVES: Our purpose is to investigate cognitive performance and
      extrapyramidal function early after ecstasy use. BACKGROUND: Ecstasy, containing
      3,4 methylenedioxymethamphetamine, has shown evidence of causing cognitive
      deficits and parkinsonian signs. Previous research has examined cognitive
      performance after a period of prolonged abstinence, but research assessing the
      early effects of ecstasy after recent use is limited despite temporal
      neurochemical differences demonstrated in nonhuman models. METHODS: This study
      compared task performance between 13 ecstasy users (10 to 15 h postdrug use) and
      a control group on a battery of neuropsychologic assessments while matching for
      education level, sleep deprivation, and premorbid IQ. The groups were also
      compared on measures relating to parkinsonian signs. RESULTS: The ecstasy
      subjects showed impairments on measures of executive function as evaluated by
      Raven's Standard Progressive Matrices (SPM) and the Wisconsin Card Sorting Task
      (WCST). Short-delay free recall memory was also impaired in ecstasy subjects on
      the California Verbal Learning Test (CVLT-II). No extrapyramidal motor
      impairments were detected. CONCLUSIONS: These deficits resemble deficits
      previously reported in chronic ecstasy use but also seem to reveal transient
      impairments in executive function. Future research is needed to better understand
      the neurologic and neuropsychologic implications of ecstasy use across time and
      extent of use.

PMID- 16957496
TI  - Cortical electric response audiometry hearing threshold estimation: accuracy,
      speed, and the effects of stimulus presentation features.
AB  - OBJECTIVES: A number of stimulus presentation features of the tone burst-evoked
      N1-P2 cortical response were investigated to identify any advantage over simple
      stimulation when the test is used for hearing threshold estimation. The speed of
      establishing objective thresholds at 1, 3, and 8 kHz in both ears was also
      measured in what was designed to be an efficient test protocol, together with the
      precision of the threshold estimates with reference to subjects' conventional
      audiograms. DESIGN: Twenty-four volunteer subjects were recruited and tested by
      both behavioral and electrophysiological methods. A low-intensity, 3-kHz stimulus
      was used when the stimulus features were studied. The parameter was the N1-P2
      amplitude. RESULTS: Changing the side of presentation (randomly or by alternating
      ears), varying the interstimulus interval and inserting a 10-second recovery
      period midway though an averaging run had no demonstrable effect on response
      amplitude, both individually or in combination, contrary to earlier reports.
      Establishing the 6 threshold estimates took an average 20.6 minutes. The mean
      error in the N1-P2 threshold estimate was 6.5 dB, with no significant effect of
      frequency. After correcting for this bias, 94% of individual threshold estimates
      were within 15 dB of the behavioral threshold and 80% were within 10 dB.
      CONCLUSIONS: This study suggests that cortical electric response audiometry has a
      performance that is as good as or better than the auditory brain stem response
      for threshold estimation in adults and that sophisticated stimulation techniques
      do not appear to be required. An efficient test protocol that automates many
      laborious tasks reduces the test time to less than half that previously reported
      in the literature for this response.

PMID- 16957495
TI  - Cognitive impairment in a 65-year-old male with the fragile X-associated tremor
      ataxia syndrome (FXTAS).
AB  - OBJECTIVE: This is the first case report of a comprehensive neuropsychologic
      examination of an older man with the fragile X-associated tremor-ataxia syndrome
      (FXTAS). BACKGROUND: FXTAS, a newly identified phenotype affecting older male
      carriers of the fragile X premutation allele, is a progressive disorder marked by
      gait ataxia, action tremor, peripheral neuropathy, executive cognitive deficits,
      generalized brain atrophy, and neuronal and astrocytic intranuclear inclusion
      bodies throughout the brain. The patient previously had undergone neurologic
      evaluation, molecular analysis, and magnetic resonance imaging. METHOD: The
      patient was administered a neuropsychologic examination, assessing motor and
      somatosensory functioning, visual and spatial functioning, speech and language,
      attention, executive abilities, learning and memory, and reasoning. RESULTS: The
      patient showed a pattern of cognitive impairment characterized by essentially
      normal speech and language, moderately impaired control of attention, and
      moderate to severe deficits in working memory, executive functioning, and both
      declarative and procedural learning. Visual and spatial abilities were relatively
      unimpaired, and verbal reasoning was only mildly deficient. CONCLUSIONS: The
      findings suggest that a cognitive disorder, with especially marked executive
      cognitive function and memory deficits, accompanies FXTAS. The findings in FXTAS
      are compared with those in several other neurodegenerative disorders.

PMID- 16957497
TI  - Perilymph/modiolar communication routes in the human cochlea.
AB  - OBJECTIVES: To analyze communication routes between perilymph spaces and the
      modiolus in the human cochlea. Such pathways are of potential importance with
      regard to local inner ear drug delivery and pharmacokinetics. DESIGN: We analyzed
      the surface structure of the human cochlea, using high-resolution scanning
      electron microscopy (SEM) in macerated and freshly obtained specimens together
      with light microscopy of celloidin-embedded temporal bones. RESULTS: Combined SEM
      and light microscopy showed that perilymph and fluid spaces in the modiolar
      periphery form a common system. The modiolar wall of the scala vestibuli and
      tympani in the first and second turn is porous, forming a perilymphatic
      communication route to the perivascular and perineural spaces in the modiolus. A
      "perimodiolar lymph" or fluid space can be identified in the modiolar periphery.
      It communicates through a trabecular meshwork of porous membrane and web of
      connective tissue with the perilymph. The thin mesothelial cell sheets showed
      pores and displayed signs of vesicular activity. CONCLUSIONS: This canalicular
      system may play a role in the circulation of perilymph in the human cochlea. We
      suggest that this system may represent an important fluid communication route
      between modiolus and perilymph and may represent a pathway for future drug and
      cell-based therapy to the inner ear.

PMID- 16957498
TI  - Repeatability of high-frequency distortion-product otoacoustic emissions in
      normal-hearing adults.
AB  - OBJECTIVES: Distortion-product otoacoustic emissions (DPOAEs) are repeatable over
      time at lower frequencies (<or=8 kHz). The purpose of this study was to examine
      the repeatability of DPOAEs measured with high-frequency stimuli in normal
      hearing adult subjects. It was hypothesized that high-frequency DPOAEs would be
      repeatable over a minimum of 4 wk. DESIGN: DPOAEs were measured in 25 subjects
      (14 female and 11 male) with normal behavioral thresholds, normal middle ear
      function, and present acoustic reflexes at 1 kHz evoked by contralateral
      stimulation. Behavioral thresholds were measured through 16 kHz, using Bekesy
      tracking. Each subject attended four trials, in which a complete set of data was
      collected. The four trials were separated by at least one, but no more than 2 wk.
      At each trial, two different DPOAE paradigms were completed. Frequency and ratio
      sweeps were used to measure DPOAE levels and calculate DPOAE group delay,
      respectively. Frequency sweeps were measured with varied stimulus level
      conditions (L1/L2 = 60/45, 60/50, 70/55, 70/60 dB SPL) and an f2/f1 of 1.2 at
      discrete f2 frequencies between 2 and 16 kHz. Ratio sweeps were obtained at f2
      frequencies of 2, 4, 6, 8, 10, 12, 14, and 16 kHz, with L1 = 60 and L2 = 45 dB
      SPL, and the ratio (f2/f1) was varied from 1.05 to 1.3. Repeated-measures
      analysis of variance was performed. RESULTS: Greater variability was found at the
      higher frequencies (>8 kHz) for DPOAE level measurements. The average DPOAE level
      differences-between-trials for the higher and lower frequencies for the four
      different stimulus level conditions was 5.15 (SD = 4.40 dB) and 2.80 (SD = 2.70
      dB) dB, respectively. Individual subject analysis revealed that high-frequency
      DPOAE levels varied no more than 10 dB for 87.5 and 83.1% of young adult subjects
      for the 70/55 and 60/50 dB SPL stimulus level conditions, respectively. For low
      frequencies, repeated DPOAE level variations were within +/-10 dB for 98.4 and
      96% of young adult subjects for the 70/55 and 60/50 dB SPL stimulus level
      conditions, respectively. For DPOAE group delay, greater variability was noted at
      lower frequencies (<or=8 kHz) and at 10 kHz. The average group-delay differences
      between-trials for the higher (10 to 16 kHz) and lower (<or=8 kHz) frequencies
      was 0.22 (SD = 0.20 msec) and 0.28 (SD = 0.24 msec) msec, respectively.
      Individual subject analysis revealed that DPOAE group-delay values varied no more
      than 0.70 msec for the majority of young adult subjects (96.5 and 93.5% at high
      and low frequencies, respectively). CONCLUSIONS: Even though the DPOAE level data
      obtained at frequencies greater than 8 kHz were more variable than at low
      frequencies, the higher frequencies were found to be repeatable for both
      paradigms tested. These results encourage the exploration of high-frequency DPOAE
      measures to be used as an objective test for monitoring ototoxicity in humans.
      Testing subjects receiving ototoxic therapies is a necessary step in determining
      if monitoring high-frequency DPOAEs will successfully predict ototoxic effects.

PMID- 16957499
TI  - Determination of the potential benefit of time-frequency gain manipulation.
AB  - OBJECTIVE: The purpose of this study was to determine the maximum benefit
      provided by a time-frequency gain-manipulation algorithm for noise-reduction (NR)
      based on an ideal detector of speech energy. The amount of detected energy
      necessary to show benefit using this type of NR algorithm was examined, as well
      as the necessary speed and frequency resolution of the gain manipulation. DESIGN:
      NR was performed using time-frequency gain manipulation, wherein the gains of
      individual frequency bands depended on the absence or presence of speech energy
      within each band. Three different experiments were performed: (1) NR using ideal
      detectors, (2) NR with nonideal detectors, and (3) NR with ideal detectors and
      different processing speeds and frequency resolutions. All experiments were
      performed using the Hearing-in-Noise test (HINT). A total of 6 listeners with
      normal hearing and 14 listeners with hearing loss were tested. RESULTS: HINT
      thresholds improved for all listeners with NR based on the ideal detectors used
      in Experiment I. The nonideal detectors of Experiment II required detection of at
      least 90% of the speech energy before an improvement was seen in HINT thresholds.
      The results of Experiment III demonstrated that relatively high temporal
      resolution (<100 msec) was required by the NR algorithm to improve HINT
      thresholds. CONCLUSIONS: The results indicated that a single-microphone NR system
      based on time-frequency gain manipulation improved the HINT thresholds of
      listeners. However, to obtain benefit in speech intelligibility, the detectors
      used in such a strategy were required to detect an unrealistically high
      percentage of the speech energy and to perform the gain manipulations on a fast
      temporal basis.

PMID- 16957500
TI  - Effects of stimulus level on the speech perception abilities of children using
      cochlear implants or digital hearing aids.
AB  - OBJECTIVE: The present investigation was designed to provide information to
      facilitate the decision of whether a child should continue using digital signal
      processing (DSP) hearing aids with wide dynamic range compression (WDRC) or be
      recommended for a cochlear implant, based on the unaided pure-tone average (PTA
      at 500, 1000, and 2000 Hz). DESIGN: Fifty-two children (ages 5 to 15 yr) with
      unaided PTAs in the moderately severe to profound range, wearing (DSP) hearing
      aids with (WDRC) or a Nucleus 24, Clarion 1.2, or CII cochlear implant system,
      participated: 26 with unaided PTAs from 60 to 98 dB HL using DSP hearing aids and
      26 with pre-implant unaided PTAs from 93 to 120 dB HL, using cochlear implants.
      An open-set speech perception test, the Lexical Neighborhood Test (LNT; ), was
      administered at intensity levels representative of raised (70 dB SPL) and soft
      (50 dB SPL) speech at two different times approximately 1 mo apart. Minimum
      audibility of soft sounds was determined for the children with implants and with
      DSP hearing aids using warble-tone thresholds at octave intervals between 250 and
      4000 Hz. RESULT: Regression analyses and significance testing were used to
      determine the unaided PTA values at which the performance of the DSP Hearing Aid
      group (DSP HA group) and Cochlear Implant group on the LNT test were
      statistically different at the 0.05 significance level. For the 70 dB SPL
      presentation level, the statistically different PTAs were 113 and 97 dB HL at
      Time 1 and Time 2, respectively, and 96 and 88 dB HL at 50 dB SPL for Time 1 and
      Time 2, respectively. CONCLUSIONS: The Unaided PTA at which children in the
      cochlear implant group would be expected to score significantly better than the
      children in the DSP HA group was lowest (96 and 88 dB HL) for the lower signal
      level (50 dB SPL). Assuming that LNT scores at 50 dB SPL are representative of
      long-term hearing of soft incidental speech that is essential for language
      learning and fluent communication, the children with PTA values greater than the
      range from 88 to 96 dB HL would be expected to have significantly better LNT
      scores with a cochlear implant. These results should be further examined with
      research efforts focusing on early intervention with optimally fitted DSP hearing
      aids and cochlear implants.

PMID- 16957501
TI  - Determining the cause of hearing loss: differential diagnosis using a comparison
      of audiometric and otoacoustic emission responses.
AB  - OBJECTIVE: The purpose of this study was to further investigate the possibility
      of developing noninvasive methods of differential diagnosis of hearing disorders
      through the study of experimental animals with induced lesions. In particular, it
      was desired to compare distortion product otoacoustic emission (DPOAE) responses
      and auditory brain stem response (ABR) thresholds in Mongolian gerbils having
      either acoustic or strial damage, using as a reference the same responses
      measured in a control group of normal young adult gerbils. The goal was to
      evaluate the potential clinical application of this approach to determining the
      dominant contribution to sensorineural hearing loss in individual human subjects.
      DESIGN: DPOAE input-output functions and ABR thresholds were measured over a wide
      range of stimulus frequencies for three groups: (1) a reference group of normal
      young adult gerbils; (2) a group in which acoustic damage had been induced 2 wk
      earlier; (3) a group in which damage to the stria vascularis was induced by a
      series of furosemide injections. The responses in the experimental groups
      relative to the normal means were compared to determine which combinations of
      responses were effective in discriminating between animals with different
      lesions. Three measures were evaluated in detail: the ABR threshold, the emission
      threshold at a criterion emission amplitude, and the emission amplitude at a high
      stimulus level. RESULTS: Considering cases with significant hearing loss (ABR
      thresholds elevated by 20 dB or more), the best method for distinguishing between
      the two lesions involved a two-dimensional plot comparing emission and ABR
      thresholds at the same stimulus frequencies. Acoustic damage cases were found in
      a broad region where the emission and ABR thresholds were roughly equal, whereas
      strial damage cases were found in a narrower region where the emission threshold
      was about 0.4 times the ABR threshold (both in dB). These two cases were compared
      with a third case introduced by definition, that is, damage to inner hair cell or
      neural systems resulting in an increase in audiometric threshold but no change in
      emission responses (e.g., auditory neuropathy). The responses for these three
      cases were found to lie in different regions of the two-dimensional plot
      comparing emission and ABR thresholds, provided only that ABR thresholds were
      elevated 20 dB or more. This diagram also revealed cases of preclinical acoustic
      damage, in which the ABR threshold was shifted less than 20 dB but where the
      emission threshold was significantly elevated. CONCLUSIONS: The results clearly
      demonstrate the possibility of developing a clinical method of noninvasive
      differential diagnosis of hearing loss. The method demonstrated was to add to a
      standard audiometric evaluation the measurement of DPOAE growth functions over
      the range of frequencies where these emissions were relatively easy to measure
      and consistent. The DPOAE stimulus frequencies were chosen to match the
      audiometric frequencies, and the corresponding emission and audiometric
      thresholds were compared on a threshold-threshold plot for each individual at a
      number of stimulus frequencies. Responses in different regions in this plot were
      found to correspond to different types of sensorineural hearing loss.

PMID- 16957502
TI  - Methodological issues when comparing hearing thresholds of a group with
      population standards: the case of the ferry engineers.
AB  - OBJECTIVES: To discuss appropriate and inappropriate methods for comparing
      distributions of hearing thresholds of a study group with distributions in
      population standards and to determine whether the thresholds of Washington State
      Ferries engineers are different from those of men in the general population,
      using both frequency-by-frequency comparisons and analysis of audiometric shape.
      DESIGN: The most recent hearing conservation program audiograms of 321 noise
      exposed engineers, ages 35 to 64, were compared with the predictions of Annexes
      A, B, and C from ANSI S3.44. There was no screening by history or otoscopy; all
      audiograms were included. 95% confidence intervals (95% CIs) were calculated for
      the engineers' median thresholds for each ear, for the better ear (defined two
      ways), and for the binaural average. For Annex B, where 95% CIs are also
      available, it was possible to calculate z scores for the differences between
      Annex B and the engineers' better ears. Bulge depth, an audiometric shape
      statistic, measured curvature between 1 and 6 kHz. RESULTS: Engineers' better-ear
      median thresholds were worse than those in Annex A but (except at 1 kHz) were as
      good as or better than those in Annexes B and C, which are more appropriate for
      comparison to an unscreened noise-exposed group like the engineers. Average bulge
      depth for the engineers was similar to that of the Annex B standard (no added
      occupational noise) and was much less than that of audiograms created by using
      the standard with added occupational noise between 90 and 100 dBA. CONCLUSIONS:
      Audiograms from groups that have been selected for a particular exposure, but,
      without regard to severity, can appropriately be compared with population
      standards, if certain pitfalls are avoided. For unscreened study groups with
      large age-sex subgroups, a simple method to assess statistical significance,
      taking into consideration uncertainties in both the study group and the
      comparison standard, is the calculation of z scores for the proportion of better
      ear thresholds above the Annex B median. A less powerful method combines small
      age-sex subgroups after age correction. Small threshold differences, even if
      statistically significant, may not be due to genuine differences in hearing
      sensitivity between study group and standard. Audiometric shape analysis offers
      an independent dimension of comparison between the study group and audiograms
      predicted from the ANSI S3.44 standard, with and without occupational noise
      exposure. Important pitfalls in comparison to population standards include
      nonrandom selection of study groups, inappropriate choice of population standard,
      use of the right and left ear thresholds instead of the better-ear threshold for
      comparison to Annex B, and comparing means with medians. The thresholds of the
      engineers in this study were similar to published standards for an unscreened
      population.

PMID- 16957503
TI  - Speech reception thresholds in noise and self-reported hearing disability in a
      general adult population.
AB  - OBJECTIVE: The principal objective of this study was to describe speech reception
      thresholds in noise (SRTTn, i.e., the signal-to-noise ratio corresponding to 50%
      intelligibility) and self-reported hearing disability in a general adult
      population. A secondary objective was to investigate to what extent the
      functional measurements could be predicted on the basis of the self-reported
      data. DESIGN: The sample consisted of 1086 subjects over 60 yr of age who
      participated in the Longitudinal Aging Study Amsterdam and 128 younger adults,
      mainly between 20 and 30 yr of age. Subjects were given a diotic speech-in-noise
      test by telephone to estimate the SRTTn and filled in a questionnaire to allow
      determination of the self-reported hearing disability. The SNR loss (signal-to
      noise ratio loss), defined as the amount by which the measured SRTTn exceeds that
      for subjects with normal hearing, was determined and classified in three hearing
      status categories: good, insufficient, and poor. RESULTS: The median SNR loss for
      the 60- to 64-year age group was 2.2 dB for men and 1.2 dB for women. The
      corresponding figures for the 80- to 84-year age group were 5.0 dB and 3.6 dB,
      respectively. Only 42% of the subjects with poor hearing possessed hearing aids.
      A single question from the self-reported hearing disability questionnaire could
      be used to predict the hearing-status category corresponding to the results of
      the speech-in-noise test correctly in 62% of the cases. Use of all five of the
      questions from the questionnaire allowed 69% of the subjects to be classified
      correctly. There is a strong effect of age on the relation between reported
      hearing disability and SNR loss. CONCLUSIONS: SNR loss is a common disability in
      people aged 60 yr or more. Relatively few people with significant SNR loss have
      hearing aids. Screening for SNR loss with a speech-in-noise test performed by
      telephone is preferable to use of a short questionnaire, even when an age
      specific scoring method is applied.

PMID- 16957504
TI  - Experimental evaluation of different methods of limiting the maximum output of
      hearing aids.
AB  - OBJECTIVE: A series of experiments designed to test the preferences of people
      with moderate to profound hearing losses for limiting the output of hearing aids
      by using peak clipping (PC), fast compression limiting (FCL), PC and FCL, and
      these three methods in combination with slow compression limiting (SCL) was
      conducted. DESIGN: Nineteen participants with moderate to profound sensorineural
      or mixed losses were recruited. In the first experiment, preferences for either
      PC or FCL were tested in a field trial in the participants' usual environments.A
      second experiment examined the acceptance of PC, FCL, and FCL + PC, using paired
      comparisons in a laboratory setting. The third experiment involved further paired
      comparisons in the laboratory to evaluate whether participants preferred PC, FCL,
      PC and FCL combined, or the three methods when combined with SCL. RESULTS: The
      participants showed no statistically significant preferences for either peak
      clipping or fast compression limiting in the field trial. In the laboratory
      trial, both FCL + PC and FCL were significantly preferred over PC alone, and the
      addition of FCL to PC was most advantageous to participants who required the
      lowest maximum limiting output. The most dramatic laboratory result was the
      convincing preference in paired comparison testing of combining SCL with PC
      and/or FCL. CONCLUSIONS: Slow compression limiting appears to be a desirable
      feature in hearing aids for clients with a moderate to profound hearing loss.
      Preferences were not as pronounced when peak clipping, fast compression limiting,
      and peak clipping plus fast compression limiting were compared, but participants
      favored the condition that had the least amount of peak clipping.

PMID- 16957505
TI  - Hearing-impaired children in the United Kingdom, III: cochlear implantation and
      the economic costs incurred by families.
AB  - OBJECTIVES: This article addresses two questions. First, are there differences in
      the economic costs incurred by families of hearing-impaired children depending on
      whether or not children have cochlear implants? Second, are these differences
      important when assessed from the perspective of society? METHODS: In a cross
      sectional survey, parents of a representative sample of hearing-impaired children
      provided data about annual resources used by the family because of their child's
      hearing impairment. The data yielded estimates of two variables: out-of-pocket
      expenditure and time away from normal activities by parents. The economic cost of
      the two variables was estimated in euros at 2001/2 price levels, and summed to
      estimate the overall economic cost incurred by the family. Linear regression was
      used to estimate the association between costs and implantation, while
      controlling for average (unaided, preoperative) hearing level, age at onset of
      hearing impairment, age, gender, the number of additional disabilities, parental
      occupational skill level, ethnicity, and parental hearing status. The cumulative
      economic cost incurred by the families of implanted children, between
      implantation and age 16 yr, was calculated from estimates of the overall economic
      cost associated with implantation and compared with estimates of the incremental
      health-sector cost of implantation. RESULTS: Data were provided by the families
      of 2858 children, 468 of whom had received a cochlear implant. Compared with the
      families of nonimplanted children, out-of-pocket expenditure was estimated to be
      significantly higher for families when children were implanted before the age of
      5 yr and had used their implant for less than 2 yr, as was lost productivity when
      children had used their implants for less than 2 yr. Overall economic cost was
      estimated to be significantly higher for the families of implanted children who
      had used their implants for less than 2 yr. The cumulative economic cost was
      estimated to be 3355 euros for a family whose child was implanted at age 3 yr and
      949 euros for a child implanted at age 6 yr. These costs correspond, at most, to
      3% of the incremental health-sector costs of implantation. CONCLUSIONS: Compared
      with families of nonimplanted children, families of implanted children incur
      additional costs in the 2 yr after implantation. These costs are small in
      relation to the health-sector costs of providing implantation.

PMID- 16957506
TI  - Hearing-impaired children in the United Kingdom, IV: cost-effectiveness of
      pediatric cochlear implantation.
AB  - OBJECTIVE: To estimate the cost-effectiveness of pediatric cochlear implantation
      by conducting a cost-utility analysis from a societal perspective. DESIGN: In a
      cross-sectional survey, the parents of a representative sample of hearing
      impaired children assessed the health utility of their child using a revised
      version of the Health Utilities Index Mark III questionnaire. Linear regression
      was used to estimate the gain in health utility associated with implantation
      while controlling for eight potentially confounding variables: average (4
      frequency, unaided, preoperative) hearing level (AHL), age at onset of hearing
      impairment, age, gender, number of additional disabilities, parental occupational
      skill level, ethnicity, and parental hearing status. The gain in health utility
      was accumulated to estimate the number of quality-adjusted life years (QALYs)
      that would be gained from implantation over 15 yr and over a child's lifetime.
      The incremental societal cost of implantation, calculated in euros at 2001/2
      levels, was estimated by summing the incremental costs of implantation that are
      incurred in the health sector, in the education sector, and by the child's
      family. The cost-effectiveness of cochlear implantation was estimated by
      calculating the incremental societal cost per QALY gained and was compared with
      an upper limit of acceptability of 50,000 euros per QALY. RESULTS: The parents of
      403 implanted children, and 1863 nonimplanted children, completed the health
      utility questionnaire. Higher health utility was associated with a more favorable
      AHL, an older age at onset of hearing impairment, female gender, having fewer
      additional disabilities, having parents with a greater occupational skill level,
      white ethnicity, and implantation. The gain in health utility associated with
      implantation was estimated to be higher for children with a worse preoperative
      AHL and who were implanted when younger. Over 15 yr, for a child implanted at age
      6 with a preoperative loss of 115 dB, 2.23 QALYs were estimated to be gained,
      compared with a mean incremental societal cost of 57,359 euros, yielding a mean
      cost per QALY of 25,629 euros. Cost-effectiveness was more favorable: (1) when
      estimated over a child's lifetime rather than 15 yr, (2) for children with a
      worse preoperative AHL, and (3) for children who were implanted when younger.
      CONCLUSIONS: The mean cost of gaining a QALY for the children in the present
      sample falls within acceptable limits. The strategy of giving highest priority
      for implantation to children with the greatest loss of hearing, and who are
      younger, maximizes benefit for a given cost.

PMID- 16957507
TI  - Treatment for hepatitis C virus and cannabis use in illicit drug user patients:
      implications and questions.
AB  - Illicit drug users are the primary risk group for HCV transmission, and will form
      the largest HCV treatment population for years to come. Sylvestre et al.'s study
      suggests that cannabis use may benefit treatment retention and outcomes in
      illicit drug users undergoing HCV treatment. In fact, there is substantial
      evidence that cannabis use may help address key challenges faced by drug users in
      HCV treatment (e.g., nausea, depression), especially when such treatment occurs
      in the context of methadone maintenance treatment which may amplify these
      consequences. While further research is required on the biological and clinical
      aspects of the benefits of cannabis use for HCV treatment, and the effectiveness
      of cannabis use for HCV treatment needs to be explored in larger study
      populations, we advocate that in the interim existing barriers to cannabis use
      are removed for drug users undergoing HCV treatment until the conclusive
      empirical basis for evidence-based guidance is available.

PMID- 16957508
TI  - Lichen planus in the oesophagus: are we missing something?
AB  - Lichen planus of the oesophagus is rare with a predilection for middle-aged to
      elderly women. There is a potential risk of malignant transformation to squamous
      cell carcinoma. Squamous cell carcinoma of the oesophagus still accounts for 30
      40% of oesophageal cancer cases in the west and is almost exclusively the disease
      still encountered in the rest of the world. An increased awareness of oesophageal
      lichen planus is suggested in patients with cutaneous, oral or vulval disease.
      Endoscopic investigation of patients with lichen planus, possibly initially
      limited to those with oesophageal symptoms, and consideration of surveillance in
      patients with proven oesophageal lichen planus, will aid understanding of natural
      history of lesions and may help detect early stage tumours. Squamous cell
      carcinoma still accounts for 30-40% of oesophageal cancer cases in the west and
      is almost exclusively the disease still encountered elsewhere. Lichen planus of
      the oesophagus is potentially a premalignant condition for squamous cell
      carcinoma that could be surveilled in order to detect early-stage tumours with a
      consequent greater chance of cure. Oesophageal lichen planus is, however, rare,
      frequently asymptomatic and although the majority of cases occur in conjunction
      with lichen planus in other sites, the oesophageal features may be subtle and
      easily missed by endoscopic assessment. Furthermore, the histological changes are
      difficult to interpret and there may be significant underreporting. As a
      consequence, the true prevalence of these lesions is hard to determine. The
      difficulties in detection may mean that we are underestimating the frequency of
      oesophageal lichen planus. Endoscopic detection may be aided by the use of
      magnification indigo carmine chromoendoscopy and this warrants further
      evaluation. The risk of malignant transformation is currently unknown but may
      parallel that of oral lesions at approximately 1-3%. An increased awareness of
      the condition can only help to identify more cases and increase our understanding
      of this interesting condition.

PMID- 16957509
TI  - Pathogenesis of diarrhea in the adult: diagnostic challenges and life-threatening
      conditions.
AB  - The mechanisms that regulate ionic balance, fluid absorption and secretion in the
      gastrointestinal tract are complex. Disturbance of this homeostatic state by bile
      acids, bacterial enterotoxins and neoplasm-derived secretagogues, for example,
      can lead to diarrhea. Determining the causes of chronic diarrhea in individual
      patients may, therefore, represent a diagnostic challenge. The gastrointestinal
      tract has finely tuned mechanisms to maintain ionic balance, fluid absorption and
      secretion. To achieve this homeostasis, various ionic transport
      proteins/complexes are targeted to the apical, basal or basolateral membranes of
      epithelial cells. Na, K and Cl ion transport proteins are regulated by endogenous
      activators (e.g. cAMP, PGE2, Ca), dietary-related factors (e.g. bile acids) and
      through post-translational modifications (e.g. phosphorylation). In certain
      pathophysiologic states, this homeostatic ionic/fluid exchange becomes
      dysfunctional as a result of failure of compensatory pro-absorptive/anti
      secretory mechanisms. The excessive secretion of Na and Cl ions followed by the
      release of a large amount of H2O into the colonic lumen results in diarrhea,
      which may be acute or chronic, and can be life-threatening if not ameliorated.
      Diverse infectious organisms (e.g. bacteria, protozoa, viruses) utilize different
      mechanisms to cause intestinal disease and diarrhea. These pathophysiologic
      mechanisms include alterations in ion transport, disruption of tight junctions
      and elicitation of inflammatory responses. Studies of patients infected with
      certain pathogens, those with ulcerative colitis and those harboring extra
      colonic or colonic neoplasms have elucidated some of these pathophysiologic
      mechanisms of diarrhea. Determining the etiology of chronic diarrhea in specific
      cases may be a diagnostic challenge for both gastroenterologists and primary care
      physicians.

PMID- 16957510
TI  - 'Biliary stenting alone versus biliary stenting plus sphincterotomy for the
      treatment of post-laparoscopic cholecystectomy bile leaks'.
AB  - Strong evidence is presented in this randomized, prospective study that biliary
      stenting alone is as effective as biliary stenting with sphincterotomy in the
      treatment of uncomplicated post-laparoscopic cholecystectomy bile leaks.

PMID- 16957511
TI  - Cannabis use improves retention and virological outcomes in patients treated for
      hepatitis C.
AB  - OBJECTIVES: Despite the widespread use of polypharmacy, the management of
      hepatitis C virus (HCV) treatment-related side-effects is often incomplete, and
      many patients turn to cannabis for symptom relief. Unfortunately, there are few
      data about cannabis use on treatment outcomes, leaving clinicians without the
      data needed to inform recommendations. METHODS: To define the impact of cannabis
      use during HCV treatment, we conducted a prospective observational study of
      standard interferon and ribavirin treatment in 71 recovering substance users, of
      whom 22 (31%) used cannabis and 49 (69%) did not. RESULTS: Seventeen of the 71
      study patients (24%) discontinued therapy early, one cannabis user (5%) and 16
      non-users (33%) (P=0.01). Overall, 37 patients (52%) were end-of-treatment
      responders, 14 (64%) cannabis users and 23 (47%) non-users (P=0.21). A total of
      21 out of 71 (30%) had a sustained virological response: 12 of the 22 cannabis
      users (54%) and nine of the 49 non-users (18%) (P=0.009), corresponding to a post
      treatment virological relapse rate of 14% in the cannabis users and 61% in the
      non-users (P=0.009). Overall, 48 (68%) were adherent, 29 (59%) non-users and 19
      (86%) cannabis users (P=0.03). Although cannabis users were no more likely than
      non-users to take at least 80% of the prescribed interferon or ribavirin, they
      were significantly more likely to remain on HCV treatment for at least 80% of the
      projected treatment duration, 95 versus 67% (P=0.01). CONCLUSIONS: Our results
      suggest that modest cannabis use may offer symptomatic and virological benefit to
      some patients undergoing HCV treatment by helping them maintain adherence to the
      challenging medication regimen.

PMID- 16957512
TI  - Occurrence of post-transplant lymphoproliferative disorders among over thousand
      adult recipients: any role for hepatitis C infection?
AB  - BACKGROUND: Post-transplant lymphoproliferative disorders represent an
      increasingly important complication of organ transplantation. Although the
      majority of the post-transplant lymphoproliferative disorder are etiologically
      related to Epstein-Barr virus infection other factors may play a role. Hepatitis
      C virus may induce clonal expansion of B-lymphocytes and has been associated with
      extrahepatic lymphoproliferative disorders. OBJECTIVES: In this study, we have
      evaluated: (i) the prevalence of post-transplant lymphoproliferative disorder;
      (ii) presence of Epstein-Barr virus in post-transplant lymphoproliferative
      disorder tissue; and (iii) the potential association between post-transplant
      lymphoproliferative disorder development and hepatitis C virus infection in a
      large cohort of adult solid organ transplant recipients. METHODS: The study
      involved 1011 liver, heart and kidney-transplanted patients. Different
      immunosuppression therapy was recorded from all patients, all were screened for
      hepatitis C virus infection. When post-transplant lymphoproliferative disorder
      developed, Epstein-Barr virus encoded RNA by in-situ hybridization and EBNA-1 and
      gp220 by polymerase chain reaction was assessed in tissue samples. RESULTS: The
      overall prevalence of post-transplant lymphoproliferative disorder was 1.4% (2.5%
      in heart, 0.9% in liver and 0.8% in kidney-transplanted patients) and
      significantly higher in hepatitis C virus positive than in hepatitis C virus
      negative patients (3.6 % vs 1.2 %; P=0.04). Epstein-Barr virus was present in 10
      (77%) out of 13 tumors tested. Two out of three Epstein-Barr virus-negative post
      transplant lymphoproliferative disorder developed in hepatitis C virus-positive
      patients. Thirteen out of 15 (86%) post-transplant lymphoproliferative disorder
      patients had undergone antithymocyte globulin/OKT3 induction therapy.
      CONCLUSIONS: Epstein-Barr virus, induction immunosuppression, rejection therapy
      and also hepatitis C virus infection may play a role in the multifactorial
      pathogenesis of post-transplant lymphoproliferative disorder.

PMID- 16957513
TI  - Influence of antitumor drugs on the expression of Fas system in SW480 colon
      cancer cells.
AB  - AIMS: To observe the influence of popular antitumor drugs [5-fluorouracil (5-FU),
      mitomycin (MMC), cisplatin (CP) and all-trans retinoic acid (ATRA)] on the
      expression of Fas system in SW480 colon cancer cells. METHODS: The expressions of
      Fas/FasL protein and mRNA in colon cancer line SW480 cells before and after the
      treatment of the antitumor drugs (5-FU, MMC, CP and ATRA) were detected by
      immunocytochemistry, flow cytometry and reverse-transcriptase polymerase chain
      reaction. Coculture assays of colon cancer cells and Jurkat cells (Fas-sensitive
      cells) were performed to observe the counterattack of colon cancer cells to
      lymphocytes. Apoptosis of Jurkat cells were detected by flow cytometry and
      fluorescence microscopy. RESULTS: SW480 expressed high FasL and low Fas without
      drug treatments. When treated with 5-FU, Fas expression rates in SW480 increased,
      but FasL remained unchanged. Both Fas and FasL increased significantly when
      treated with MMC and CP. Most importantly, ATRA could induce SW480 cells to
      differentiate, increase the expression of Fas and decrease the expression of
      FasL. The coculture of SW480 cells and Jurkat cells confirmed the function of
      FasL in the SW480 cells. CONCLUSION: Certain antitumor drugs can change the
      expression of the Fas system in SW480 cells in different ways. In vitro, MMC and
      CP can increase the sensitivity of colon cancer cells to apoptosis signals, but
      they possibly facilitate immune escape of tumor cells. 5-FU results in immune
      escape of colon cancer cells. ATRA can down-regulate the possibility of
      counterattack of colon cancer cells.

PMID- 16957514
TI  - Many participants in fecal occult blood test population screening have a higher
      than-average risk for colorectal cancer.
AB  - OBJECTIVES: Population-based colorectal cancer screening by fecal occult blood
      testing reduces cancer-specific mortality. Current guidelines recommend this
      strategy for average risk individuals. This study investigated the prevalence of
      higher-than-average risk characteristics, and rate of prior colonoscopy, in
      participants in fecal occult blood test screening programs. METHODS: Randomly
      selected individuals aged 50-74 years in urban Adelaide were offered free fecal
      occult blood test screening by mail, without prior knowledge of their medical
      status. Each invitation included a questionnaire to record the prevalence of
      higher-than-average risk characteristics related to symptoms, family history or
      comorbidity, as well as prior colonoscopy. The definition of average risk was
      taken from updated guidelines published by the US Multisociety Task Force on
      Colorectal Cancer. RESULTS: Of 2538 responses analyzed, 425 individuals had had a
      colonoscopy within the last 5 years, 106 fulfilled family history criteria for an
      initial screening colonoscopy, 209 had past polyps and 26 had had colorectal
      cancer. Eighty-three reported recent rectal bleeding. By current guidelines, 23%
      of the screened population did not warrant fecal occult blood test, because
      either prior colonoscopy rendered it unnecessary or particular patient
      characteristics made colonoscopy a more appropriate initial investigation.
      CONCLUSIONS: Fecal occult blood test screening programs capture a sizeable number
      of higher-than-average risk individuals that may warrant colonoscopic rather than
      fecal occult blood test screening. Other participants have had a recent
      colonoscopy and probably warrant a delay in screening. Mass population fecal
      occult blood test-based screening programs need to more effectively target those
      at average risk and should divert those of higher or lower risk to more
      individualized assessment.

PMID- 16957515
TI  - The gastric mucosa in gastric cancer patients in a low-incidence area.
AB  - BACKGROUND AND AIMS: Atrophic gastritis, intestinal metaplasia, and pyloric
      metaplasia are frequent precursors of noncardial intestinal-type gastric
      adenocarcinoma in populations in which both gastric cancer and Helicobacter
      pylori infection are common. We hypothesized that such lesions would be less
      prevalent in European gastric cancer patients. METHODS: Slides from patients who
      underwent gastrectomy for adenocarcinoma between 1997 and 2004 were reviewed.
      Tumors were categorized as intestinal or diffuse; non-neoplastic mucosa was
      evaluated for gastritis, atrophy, intestinal metaplasia and pyloric metaplasia.
      RESULTS: We studied 81 patients: 48 Swiss (mean age 68.5 years); 17 Italians
      (mean age 67.8 years); and 16 Iberians (mean age 54.8 years; P<0.001). Twelve
      tumors were proximal (all intestinal type), 12 in the corpus (six intestinal
      type), and 57 antral (30 intestinal type). Patients with diffuse cancers were
      younger than those with intestinal type (P<0.05). Nineteen patients (23.4%) had a
      normal stomach; 30% of T1 tumors and 90% of T4s arose in a normal stomach
      (P<0.02). H. pylori gastritis was found in 47 patients (58%); they did not differ
      in age, sex, national origin, cancer location or type from those without
      gastritis. Intestinal metaplasia correlated with H. pylori gastritis (P=0.002).
      Pyloric metaplasia was infrequent and limited to rare microfoci. CONCLUSIONS: A
      quarter of the patients had a normal stomach, and pyloric metaplasia was
      distinctly uncommon. Approaches to prevention and early detection of gastric
      cancer based on bioptic or serological demonstration of atrophy and metaplasia
      could overlook at least 25% of the people at risk in certain populations and may
      need to be adapted to local conditions.

PMID- 16957516
TI  - Budesonide treatment and expression of inducible nitric oxide synthase mRNA in
      colonic mucosa in collagenous colitis.
AB  - OBJECTIVE: In collagenous colitis, the production of nitric oxide in the colon is
      found to be 50 to 100-fold higher than in healthy controls. The role of nitric
      oxide in collagenous colitis is debated and it has been suggested that nitric
      oxide has a causative role in diarrhoea. The aim of this study was to examine the
      possible effect of budesonide treatment on the level of inducible nitric oxide
      synthase mRNA. METHODS: In 20 patients with collagenous colitis, clinical
      activity was assessed by registration of the daily stool frequency and stool
      weight. Sigmoidoscopy was performed and biopsies for histological examination and
      one biopsy for determination of inducible nitric oxide synthase mRNA was obtained
      in 16 patients. RESULTS: Budesonide treatment was followed by a significant
      reduction of inducible nitric oxide synthase mRNA (P<0.01) whereas no change was
      observed after placebo treatment. Significant correlations between inducible
      nitric oxide synthase mRNA and the grade of inflammation (rho=0.47; P<0.01), the
      daily stool weight (rho=0.51; P<0.005) and the daily stool frequency (rho=0.49;
      P<0.005) were observed. No significant association was observed between inducible
      nitric oxide synthase mRNA and the thickness of the collagen layer. CONCLUSIONS:
      In patients with collagenous colitis, treatment with budesonide results in a
      reduction of inducible nitric oxide synthase mRNA. The level of inducible nitric
      oxide synthase mRNA in colonic mucosa correlates with the inflammatory and
      clinical activity. The results support that nitric oxide is a central factor in
      the pathogenesis of collagenous colitis.

PMID- 16957517
TI  - Somatization an independent psychosocial risk factor for irritable bowel syndrome
      but not dyspepsia: a population-based study.
AB  - BACKGROUND: A psychosocial conceptualization for irritable bowel syndrome and
      unexplained dyspepsia has been proposed, but remains untested. We conducted a
      comprehensive population-based study to determine what psychiatric and
      psychosocial factors, if any, are important in irritable bowel syndrome and
      dyspepsia. METHODS: Two hundred and seven participants identified from two
      previous Australian population surveys who also met Rome I criteria for irritable
      bowel syndrome (n=156) or unexplained dyspepsia (n=51) were included in the
      study. Consulters (n=103) were those who had had visited their general
      practitioner for gastrointestinal symptoms at least once in the prior 12 months.
      Nonconsulters had not sought medical care for gastrointestinal symptoms in the
      past year. Controls (n=100) did not report having any abdominal pain in a
      previous population survey. Psychosocial variables were assessed using structured
      interviews and validated self-report measures. RESULTS: Psychiatric diagnoses,
      neuroticism, more highly threatening life event stress, an external locus of
      control and ineffectual coping styles were significantly associated with having a
      diagnosis of irritable bowel syndrome and/or dyspepsia. Only somatization (odds
      ratio=5.28, 95% confidence interval 1.57-17.68), however, was independently
      associated with irritable bowel syndrome. Psychosocial factors did not
      discriminate between consulters and nonconsulters. CONCLUSIONS: Somatization is
      likely play a key role in explaining irritable bowel syndrome but not dyspepsia.

PMID- 16957518
TI  - Two siblings with lichen planus and squamous cell carcinoma of the oesophagus.
AB  - Lichen planus is a mucocutaneous disease which can also affect the oesophagus.
      Unlike in oral lichen planus an increased risk for the development of squamous
      cell carcinoma in the oesophagus has not been established. We describe two
      sisters with a history of long-standing cutaneous lichen planus who developed
      oesophageal squamous cell carcinoma, diagnosed at the ages of 68 and 70 years,
      respectively. In one of the cases, dysplastic areas were identified by high
      magnification chromoendoscopy. In both cases, oesophageal resection was carried
      out with a curative intent. For the first time these sibling case reports suggest
      an increased precancerous potential of oesophageal lichen planus.

PMID- 16957519
TI  - Efficiency and safety of bosentan in child C cirrhosis with portopulmonary
      hypertension and renal insufficiency.
AB  - Bosentan has lately been described as a successful therapeutic agent for
      portopulmonary hypertension consecutive to child A cirrhosis. This is the first
      report of the effect of this substance with advanced liver cirrhosis (child C)
      and renal insufficiency. Low doses of bosentan (initially twice 31.25 mg/day and
      then 62.5 mg/day) increased cardiac output and allowed correction of renal
      insufficiency; it allowed one to stop the requirement of oxygen and not only
      improved the 6-min walking test by more than 400 m, but also decreased the
      severity of the liver cirrhosis to child B stadium. This suggests that patients,
      who would be excluded from a liver transplantation program because of their
      portopulmonary hypertension, could profit from a careful therapy with bosentan.

PMID- 16957520
TI  - Treating intravenous drug users with hepatitis C infection: an opportunity in
      some settings.

PMID- 16957523
TI  - Professional sexual misconduct and the distinction between current and former
      patients.

PMID- 16957524
TI  - Ethical drift: when good people do bad things.
AB  - There are many factors in today's healthcare environment which challenge nurses
      and nursing administration in adhering to ethical values. This article discusses
      the phenomenon of ethical drift, a gradual erosion of ethical behavior that
      occurs in individuals below their level of awareness. It is imperative for nurse
      managers and executives to be aware of the danger that workplace pressures pose
      in encouraging ethical drift at all levels of nursing, and to take steps to
      prevent this phenomena from occurring in their facilities.

PMID- 16957527
TI  - Evidence-based nursing education for regulation.

PMID- 16957525
TI  - EMTALA: the basics.
AB  - The Emergency Medical Treatment and Active Labor Act (EMTALA) is the federal
      legislation governing the transfer of patients. This law is often confusing for
      healthcare providers. For this reason, it is often difficult for providers to
      understand what elements of this law apply to their practice. This article
      outlines the EMTALA requirements to clearly relay the critical elements of this
      important piece of legislation and to illustrate how EMTALA applies to hospital
      nursing practice. All nurses in administrative and management roles need to be
      aware of the requirements of this law in order to educate and guide their nursing
      staff so that the facility remains in compliance.

PMID- 16957528
TI  - Caring theory as an ethical guide to administrative and clinical practices.
AB  - This article explores the conventional relationship between caring, economics,
      and administrative practices that no longer serve patients, practitioners, or
      systems. A shift toward human caring values and an ethic of authentic healing
      relationships is required as systems now have to value human resources and life
      purposes, inner meanings, and processes for workers and patients alike, not just
      economics alone. This shift requires a professional ethos with renewed attention
      to practice that is ethics/values-based and theory-guided, alongside evidence and
      economics. Emergent professional, caring-theory-guided practice options are
      presented, which are grounded on this deeper ethical moral and theoretical
      foundation for transforming the practitioners and the system.

PMID- 16957529
TI  - Electroconvulsive therapy and placebo effects: does full disclosure affect
      expectancy and satisfaction?

PMID- 16957530
TI  - Therapeutic and prophylactic utility of the memory-enhancing drug donepezil
      hydrochloride on cognition of patients undergoing electroconvulsive therapy: a
      randomized controlled trial.
AB  - OBJECTIVES: Substantial progress has been made in identifying how the treatment
      parameters used in electroconvulsive therapy (ECT) impact its cognitive side
      effects. However, there is limited information regarding the role of memory
      enhancers in post-ECT cognitive disturbances. We evaluated the therapeutic and
      prophylactic efficacy of the memory-enhancing drug donepezil hydrochloride on
      cognition of patients undergoing ECT. METHODS: A triple blind (the study
      subjects, clinician assessing the cognition, and the data analyst were unaware of
      subject allocation for trial assessment) randomized controlled trial was carried
      out in a General Hospital Psychiatry Unit. Subjects were randomized into 2
      groups. One group received ECT with placebo, whereas the other group received ECT
      and donepezil (a memory-enhancing drug). Study participants were assessed in post
      ECT period to analyze cognitive deficits and to compare the differences in 2
      groups, as regards recovery of various aspects of cognition. RESULTS: The post
      ECT recovery of various components of cognition was more rapid in patients using
      donepezil as compared to those not given donepezil (P < 0.05). CONCLUSIONS: This
      significant improvement in recovery time among patients receiving donepezil bears
      therapeutic implication in immediate post-ECT cognitive deficits.

PMID- 16957531
TI  - Estimating resting motor thresholds in transcranial magnetic stimulation research
      and practice: a computer simulation evaluation of best methods.
AB  - OBJECTIVES: Resting motor threshold is the basic unit of dosing in transcranial
      magnetic stimulation (TMS) research and practice. There is little consensus on
      how best to estimate resting motor threshold with TMS, and only a few tools and
      resources are readily available to TMS researchers. The current study
      investigates the accuracy and efficiency of 5 different approaches to motor
      threshold assessment for TMS research and practice applications. METHODS:
      Computer simulation models are used to test the efficiency and accuracy of 5
      different adaptive parameter estimation by sequential testing (PEST) procedures.
      For each approach, data are presented with respect to the mean number of TMS
      trials necessary to reach the motor threshold estimate as well as the mean
      accuracy of the estimates. RESULTS: A simple nonparametric PEST procedure appears
      to provide the most accurate motor threshold estimates, but takes slightly longer
      (on average, 3.48 trials) to complete than a popular parametric alternative
      (maximum likelihood PEST). Recommendations are made for the best starting values
      for each of the approaches to maximize both efficiency and accuracy. CONCLUSIONS:
      In light of the computer simulation data provided in this article, the authors
      review and suggest which techniques might best fit different TMS research and
      clinical situations. Lastly, a free user-friendly software package is described
      and made available on the world wide web that allows users to run all of the
      motor threshold estimation procedures discussed in this article for clinical and
      research applications.

PMID- 16957532
TI  - A standardized motor threshold estimation procedure for transcranial magnetic
      stimulation research.
AB  - OBJECTIVES: To introduce and to test a simple standardized motor threshold (MT)
      estimation procedure for transcranial magnetic stimulation (TMS) research.
      METHODS: A 5-step MT estimation procedure was introduced, and interestimator
      reliability was tested by comparing MTs as determined by an experienced and a
      trainee TMS researcher in a double-blind design. RESULTS: The parametric Pearson
      correlation between the MTs of the experienced and the MTs of the trainee TMS
      researcher was 0.95 (P < 0.001). CONCLUSIONS: The currently proposed estimation
      procedure may be helpful in obtaining reliable MT values in experimental and
      clinical settings.

PMID- 16957533
TI  - Anesthesia and electroconvulsive therapy: a retrospective study comparing
      etomidate and propofol.
AB  - BACKGROUND: The choice of anesthetic can influence the efficacy of
      electroconvulsive therapy (ECT). In the UK, propofol is a popular induction agent
      for ECT, but is associated with higher stimulus charge, shorter seizures, and
      known to affect seizure threshold. Etomidate is an alternative induction agent
      but there are concerns over its adverse events and safety. OBJECTIVES: We
      examined the differences between propofol and etomidate in the real life
      situation of an ECT clinic by assessing their effect on (i) length of course of
      ECT (ie, number of treatments required to remission), (ii) adverse effects of
      each induction agent, (iii) the number of 'missed seizures,' and (iv) stimulus
      dose (charge in mC), which relates to seizure threshold. METHOD: Using a
      retrospective naturalistic study design, 94 patients were identified over a 36
      month period in our ECT clinic, of which, 65 met the inclusion criteria. Of
      these, 36 had received etomidate and 29 had received propofol as induction agents
      throughout their course of ECT. RESULTS: Patients who received propofol had a
      significantly longer course of ECT, higher seizure thresholds, and increased
      amounts of electrical charge (mC) over their course. There were no significant
      differences in adverse events with either of the induction agents. CONCLUSIONS:
      When used for acute courses of ECT, propofol and etomidate are equally well
      tolerated as induction agents. Patients who received propofol had longer acute
      courses of ECT and, consequently, longer and costlier inpatient stays. Etomidate
      could be a better alternative induction agent in ECT.

PMID- 16957534
TI  - The effects of etomidate on seizure duration and electrical stimulus dose in
      seizure-resistant patients during electroconvulsive therapy.
AB  - OBJECTIVE: Methohexital used to be the preferred anesthetic used in
      electroconvulsive therapy (ECT). Since 1999, there have been supply problems for
      this drug, and there has been no clear guidance regarding which anesthetic should
      be used preferably in ECT. Most clinics use thiopental or propofol, although
      these drugs may increase the seizure threshold. We investigated if etomidate
      improves seizure duration compared with thiopental in cases where eliciting
      seizures becomes problematic. METHODS: During our routine delivery of ECT at a
      general psychiatric hospital in Cardiff, UK, we observed 5 patients who had ECT
      courses with thiopental and did not achieve adequate seizure duration despite
      very high electric stimulation. They later relapsed and received second courses
      of ECT under etomidate. We compared the seizure duration and the electric charge
      needed to produce the seizures for a total of 46 pairs of ECT sessions given
      under the 2 anesthetics on the same patients. RESULTS: The average electric
      stimulation dose required to induce seizures was reduced from 638 to 497
      millicoulombs (95% confidence interval, 60-221; P = 0.001). Despite the lower
      dose, the length of observed seizure duration increased by 10.3 seconds (65%) and
      that of the electroencephalograph-recorded duration increased by 8.7 seconds
      (41%) (P < 0.001). CONCLUSIONS: Etomidate has a distinct advantage over
      thiopental in producing seizures of adequate duration during ECT and should be
      used as the first-line measure in augmenting seizures in patients who have very
      high seizure thresholds.

PMID- 16957535
TI  - Memory performance in severely depressed patients treated by electroconvulsive
      therapy.
AB  - OBJECTIVES: Depression is accompanied by disturbed implicit (unconscious) and
      explicit (conscious) memory functions. The aim was the assessment of immediate
      and delayed verbal and visual memory functions, concentration/attention during
      the course of electroconvulsive therapy (ECT) treatment. METHODS: Twenty severely
      depressed, drug-treatment resistant, elderly patients were assessed with the
      Wechsler Memory Scale-Revised (WMS-R) before and at the end of the ECT series.
      RESULTS: Patients revealed deficits in acquisition (immediate verbal and visual
      memory), attention/concentration, and retrieval of information (delayed memory)
      before ECT. After ECT, significant improvements were observed in immediate memory
      but not in delayed memory. Although higher total stimulation levels
      (millicoulombs) (P = 0.015) were associated with improvements in immediate visual
      memory, we found that longer duration of convulsions (P = 0.016) as well as lower
      levels of stimulation at last ECT (P = 0.036) were associated with improvements
      in immediate verbal memory. Moreover, we found that stimulation energy
      (millicoulombs) in total and at last ECT was the best predictor among several
      clinical and ECT parameters of improved visual memory and concentration and
      decreased verbal and general memory. CONCLUSIONS: Prefrontal cortex-related
      memory processes, especially immediate memory encoding, improved after ECT,
      whereas long-term memory remained impaired, indicating that severely depressed
      patients remain cognitively inferior to normal subjects despite clinically
      successful treatment. This study may yield a better understanding of the time
      course of memory alterations in severely depressed patients receiving ECT.
      Improvement of immediate memory may be essential for establishing normal daily
      activities of life in the recovery phase of depression.

PMID- 16957536
TI  - Can cognitive behavioral therapy reduce relapse rates of depression after ECT? a
      preliminary study.
AB  - OBJECTIVE: The goal of this study was to explore the potential of providing
      cognitive behavioral therapy (CBT) after an index course of electroconvulsive
      therapy (ECT) for depression to improve long-term outcome. METHOD: The Beck
      Depression Inventory (BDI) and Clinical Global Impression (CGI) scale were used
      to assess depression and treatment outcome for 6 patients who received 12 weeks
      of CBT after an index course and concurrent with a continuation course of ECT.
      RESULTS: Patients either maintained their response or showed decreased depressive
      symptoms at the 6-month post-index ECT evaluation. At the 9-month follow-up, 5 of
      6 patients had BDI scores below their post-index ECT scores. The CGIs were rated
      "much improved" or "very much improved" by 5 patients at the termination of CBT.
      All 6 patients maintained or improved their CGIs at the 6-month follow-up.
      CONCLUSIONS: These results provide preliminary evidence that CBT after ECT is
      feasible and may extend the antidepressant effects ofECT.

PMID- 16957537
TI  - A retrospective controlled study into memory complaints reported by depressed
      patients after treatment with electroconvulsive therapy and pharmacotherapy or
      pharmacotherapy only.
AB  - Few studies have been conducted comparing complaints of memory problems using
      objective and subjective memory scales in depressed patients who received
      electroconvulsive therapy (ECT) + pharmacotherapy or treatment with
      pharmacotherapy only. Patients who suffer from depression according to the
      Diagnostic and Statistical Manual of Mental Disorder (Fourth Edition) criteria
      and who were admitted within the past 5 years before this study in a general
      psychiatric hospital were screened for inclusion. Objective retrograde amnesia
      was assessed using the Autobiographical Memory Interview and the Amsterdam Media
      Questionnaire (AMQ). Subjective retrograde amnesia was assessed using the Squire
      Subjective Memory Questionnaire and the ECT Retrograde Amnesia and Perception
      Scale (ERAPS), a newly developed scale. Twenty of the 84 patients who received
      ECT + pharmacotherapy and 30 of the 196 patients who received pharmacotherapy
      only participated in the study. Patients' ERAPS memory scores were compared with
      proxies' ERAPS memory scores of the patients to assess the reliability of memory
      complaints. The ECT + pharmacotherapy group was found to suffer more from memory
      problems using the AMQ 1990 test. There was also a difference for the proxy's
      ERAPS memory score, reflecting the conviction of proxies from the ECT +
      pharmacotherapy patients that these patients suffer more memory problems due to
      the illness, treatment with pharmacotherapy, or ECT. The differences could not be
      explained by the influence of determinants for retrograde amnesia. ECT +
      pharmacotherapy patients did not attribute their memory problems mainly to ECT
      but put equal "blame" on the depressive illness, treatment with pharmacotherapy,
      and ECT. The analyses suggest that the AMQ 1990s test is (more) sensitive in
      registering retrograde amnesia than the other scales used in the study.

PMID- 16957538
TI  - S100 and impact of ECT on depression and cognition.
AB  - OBJECTIVES: The main side effects of electroconvulsive therapy (ECT) are in the
      realm of cognition. The S100-beta is a calcium-binding protein that is expressed
      by astrocytes in the central nervous system during depression and has been
      suggested to modulate the impact of ECT on cognition. METHODS: Serum samples of
      S100-beta were taken before and 1 and 3 hours after each ECT session in 12
      depressed patients (mean age, 54 years), treated with bilateral ECT twice weekly
      (mean, 6 sessions). Measures of depression (Symptom Checklist-90 depression
      dimension) and a neurocognitive test battery yielding 3 domains of general
      cognition, memory, and subjective cognitive impairment were administered 1 day
      before and 5 and 30 days post-ECT. RESULTS: Electroconvulsive therapy was
      associated with a reduction in depression and subjective cognitive impairment at
      5 and 30 days post-ECT. Electroconvulsive therapy was associated with a small but
      significant rise in S100-beta 1 hour post-ECT (adjusted B = 0.013, P = 0.035),
      with a directionally similar but reduced effect size at 3 hours post-ECT
      (adjusted B = 0.010, P = 0.10). Higher level of S100-beta at baseline was
      associated with poorer memory function at 5 and 30 days of follow-up (adjusted B
      per tertile group increase, 0.38, P = 0.013) but also with less subjective
      cognitive impairment (B = -28.2, P < 0.001) and less depression at follow-up (B =
      -15, P = 0.009). CONCLUSION: The S100-beta at baseline may be a marker predicting
      and possibly mediating the differential impact of ECT on cognition and
      depression.

PMID- 16957539
TI  - Ictal electroencephalographic characteristics during electroconvulsive therapy: a
      review of determination and clinical relevance.
AB  - OBJECTIVE: The usefulness of electroencephalogram (EEG) during electroconvulsive
      therapy (ECT) is not limited to the duration of seizure. The use of studying its
      characteristics has gained attention among specialized ECT researchers. This
      review attempts to put the literature in this area of ictal EEG in ECT into a
      practical perspective. METHODS: A systematic database search using MEDLINE and
      EMBASE was performed using the keywords ECT and ictal EEG. RESULTS: Manual,
      linear, and nonlinear methods have been used to analyze EEG obtained during ECT.
      Most studies have used spectral or linear methods of analysis. Studies using
      nonlinear have been sparse. There are 4 overlapping practical applications of
      analysis of EEG during ECT. First, EEG can discriminate between electrode
      positions and more controversially different stimulus doses. Second, EEG can
      predict treatment response. Postictal suppression is the measure most studied
      from all vantage points. Nonlinear approaches to determine EEG predictors hold
      promise. Third, changes in the EEG across ECT sessions may indicate threshold
      changes and aids more optimum dosimetry. Fourth, EEG characteristics have been
      incorporated into ECT clinical algorithms, but this still remains controversial,
      and there is a paucity of studies in this area. CONCLUSIONS: The use of ictal EEG
      extends beyond determining the seizure length. The study of ictal EEG has certain
      practical uses, which could help individualize ECT treatment if applied in
      routine ECT practice.

PMID- 16957540
TI  - Concomitant use of vagus nerve stimulation and electroconvulsive therapy for
      treatment-resistant depression.
AB  - OBJECTIVE: This study explored the use of electroconvulsive therapy (ECT) in the
      pivotal study of vagus nerve stimulation (VNS) for treatment-resistant
      depression. METHODS: The clinical characteristics and outcomes of study
      participants who received ECT during the first 12 months of VNS were compared
      with those who did not receive ECT. Physicians were instructed to turn off VNS
      during administration of ECT. RESULTS: Of 205 (evaluable sample) patients who
      received VNS, 14 also received ECT. Participants who received ECT had a
      statistically significant greater number of hospital admissions (P = 0.037,
      Wilcoxon) and number of suicide attempts during their lifetimes (P= 0.022, Fisher
      exact test). Of 55 responders (> or =50% reduction in Hamilton Rating Scale for
      Depression-24 questions [HRSD-24] scores) after 12 months of VNS, 3 had received
      ECT. Of 32 remitters (HRSD-24 score, < or =9), 2 had received ECT. Administration
      of ECT did not affect the implanted VNS device, and the presence of the implanted
      VNS device did not affect the administration of ECT. CONCLUSIONS:
      Electroconvulsive therapy and VNS are not mutually exclusive. They can be used
      safely and effectively either sequentially or concurrently. Each can be
      prescribed as the depressive condition warrants-ECT for emergently worsening
      depressive symptoms and maintenance therapy and VNS for chronic, long-term
      therapy.

PMID- 16957541
TI  - Electroconvulsive therapy as an alternative treatment for obese patients with
      mood disorders.
AB  - With the increased use of atypical antipsychotic medication in the treatment of
      mood disorders, patients are increasingly experiencing side effects, such as
      obesity, insulin resistance, and the metabolic syndrome, which, in turn,
      increases the risk of developing cardiovascular disease, type 2 diabetes, and
      hypertension. Maintenance electroconvulsive therapy (MECT) can be used as a
      prophylaxis for the recurrence of mood episodes for treatment-resistant patients.
      There are no reports of metabolic syndromes associated with ECT. We reviewed the
      charts of 10 patients who have received MECT at our institution over the last 10
      year period. Five of 10 patients were obese pre-ECT, all of whom had a
      significant weight loss after ECT. Patients whose weights were normal pre-ECT,
      did not experience weight loss. Our finding suggests that ECT is a viable
      alternative for overweight patients with mood disorders who do not respond to
      mood stabilizers or cannot tolerate side effects.

PMID- 16957542
TI  - Self-administered electroconvulsive treatment with a homemade device.
AB  - Two patients with personality disorder and depression attempted to self
      administer electroconvulsive therapy with a homemade device. The patients showed
      no proper psychopathological improvement after these attempts. Both of the
      patients' temples were seriously burned, and one of them required skin grafting.
      Both patients rejected to have reasonable psychosocial support, and followed a
      cult mental health manual in attempting to self-administer electroconvulsive
      therapy. To our knowledge, this is only the second report of its kind. The
      intractable psychopathology, poor interpersonal skills, and misleading
      information seemed to lead to the self-harm behaviors of our 2 patients.

PMID- 16957543
TI  - Electroconvulsive therapy and venous angiomas: two case reports and review of the
      literature.
AB  - According to the American Psychiatric Association, the risk for complications
      related to the electroconvulsive therapy (ECT) treatment of patients with
      cerebrovascular malformations is small. The literature contains a number of case
      studies presenting the uneventful treatment of patients with cerebral aneurysms
      with ECT. However, there is a paucity of cases presenting ECT in the context of a
      cerebral venous angioma. In this article, we present 2 cases of patients treated
      with ECT who were found to have documented venous angiomas. This is followed with
      a brief review of the literature.

PMID- 16957544
TI  - Electroconvulsive therapy in India.

PMID- 16957545
TI  - The effects of blood pressure reduction on cognitive function: a review of
      effects based on pooled data from clinical trials.
AB  - OBJECTIVE: To review systematically and synthesize quantitatively the evidence
      from completed randomized, controlled trials of blood pressure reduction on
      cognitive performance. METHODS: MEDLINE, EMBASE and Cochrane databases were
      searched to identify randomized, controlled trials that measured the effect of
      blood pressure reduction on cognitive performance. Additional studies were
      identified by searching bibliographies of retrieved articles and contacting
      experts in the field. Data were extracted on study quality, blood pressure,
      performance on cognitive function tests, antihypertensive treatment regimens and
      the duration of treatment. Studies were reviewed and abstracted independently by
      two trained researchers. RESULTS: Sixteen studies with 19 501 subjects were
      identified. Modest reductions in blood pressure (< 5/3 mmHg) in 13 860 subjects
      were associated with improvements in Mini Mental State Examination score
      [weighted mean difference (WMD) = 0.19; 95% confidence interval (CI) = 0.19-0.19]
      and performance on immediate (WMD = 0.62; 95% CI = 0.21-1.02) and delayed (WMD =
      0.67; 95% CI = 0.23-1.11) logical memory tasks. However, studies in 2380 subjects
      that included tests of perceptual processing and learning capacity (trail making
      test-A, paired associated learning test) showed impaired performance (WMD = -1.12
      s; 95% CI = -1.22 to -1.02 and WMD = -0.04; 95% CI = -0.04 to -0.04) on these
      tests. CONCLUSION: Blood pressure lowering may have a heterogeneous effect on
      different aspects of cognitive function. Future studies with specific cognitive
      end-points are needed for greater clarity to guide practice.

PMID- 16957546
TI  - Accuracy of blood pressure measurement: sphygmomanometer calibration and beyond.

PMID- 16957547
TI  - Validation of in-vitro data by in-vivo evidence: the example of angiotensin (1
      7).

PMID- 16957548
TI  - Mechanics or mediators: arterial damage from high blood pressure.

PMID- 16957549
TI  - Electrocardiographic 'strain' pattern in left ventricular hypertrophy: electrical
      waves or mechanical function?

PMID- 16957550
TI  - What effect on blood pressure can we expect from continuous positive airway
      pressure treatment in obstructive sleep apnoea?

PMID- 16957551
TI  - Lack of sphygmomanometer calibration causes over- and under-detection of
      hypertension: a computer simulation study.
AB  - OBJECTIVE: To estimate the contribution of inadequate sphygmomanometer
      calibration to over- and under-detection of hypertension. DESIGN: Monte Carlo
      simulation of the measurement of blood pressure (BP) of a population with
      calibrated and uncalibrated sphygmomanometers. Simulated BP measurements included
      systematic sphygmomanometer error and random variability. MAIN OUTCOME MEASURES:
      The percentage of hypertensive adults (BP > 140/90 mmHg) not detected and the
      percentage of adults incorrectly classified hypertensive due to sphygmomanometer
      error. The percentage of the false positives and false negatives attributable to
      sphygmomanometer error. The number of additional visits patients need to make to
      obtain the same improvement in hypertension detection as is obtained by
      sphygmomanometer calibration. RESULTS: After three visits, uncalibrated
      sphygmomanometer error causes 20 and 28% of all undetected adult systolic and
      diastolic hypertension, respectively, and 15 and 31% of all falsely detected
      adult systolic and diastolic hypertension. In some groups, under-detection is
      worse; for example, sphygmomanometer error causes 27% of all missed systolic
      hypertension in 35-44-year-old females. In some age groups, over-detection is
      worse; for example, after three visits, sphygmomanometer error causes 63 and 50%
      of falsely detected systolic and diastolic hypertension in 18-24-year-old
      females, respectively. In-service sphygmomanometer calibration achieves the same
      or greater improvement in hypertension detection as an additional two visits.
      CONCLUSIONS: Uncalibrated sphygmomanometers are a preventable cause of clinically
      significant over- and under-detection of hypertension. Sphygmomanometers should
      be calibrated regularly by accredited organizations or technicians. Standards and
      guidelines governing sphygmomanometers in service should be revised.
      Sphygmomanometer calibration is a cost-effective way of improving hypertension
      detection.

PMID- 16957552
TI  - Combined effect of blood pressure and physical activity on cardiovascular
      mortality.
AB  - BACKGROUND: High blood pressure increases cardiovascular mortality, but whether
      the effect is counteracted by physical activity is not clear. METHODS: The
      combined association of blood pressure and physical activity on cardiovascular
      mortality was assessed in a cohort of 30 597 women and 30 508 men, using
      standardized blood pressure measurements and information on usual frequency,
      duration, and intensity of physical exercise. RESULTS: During 16 years of follow
      up, 1942 women and 2824 men with no history of cardiovascular disease or
      diabetes, who had never used blood pressure medication, died from cardiovascular
      causes. Cardiovascular mortality increased continuously with increasing blood
      pressure, and, at each blood pressure level, risk was higher in men and women
      with no physical activity compared with those who reported high physical
      activity. High activity combined with increasing pressure, however, yielded
      higher risk than high activity combined with normotensive pressure. Compared with
      the reference (systolic pressure 120-129 mmHg and high activity), the relative
      risk of cardiovascular death for systolic pressure of 140-159 mmHg combined with
      high activity was 1.21 (95% confidence interval, 0.97-1.52), compared with a
      relative risk of 1.73 (95% confidence interval, 1.37-2.19) in men with no
      activity. For women, the corresponding relative risks were 1.47 (95% confidence
      interval, 1.04-2.09) in the high activity group and 1.93 (95% confidence
      interval, 1.39-2.69) for no activity. The combined results for diastolic pressure
      and physical activity displayed similar patterns. CONCLUSIONS: The results
      support the hypothesis that cardiovascular health of individuals with moderate
      hypertension will benefit from regular physical exercise.

PMID- 16957553
TI  - The association between subclinical hyperthyroidism and blood pressure in a
      population-based study.
AB  - OBJECTIVE: Although evidence for an increased risk of hypertension in both overt
      hyperthyroidism and overt hypothyroidism is consistent, the relation between
      subclinical hyperthyroidism and blood pressure has not yet received sufficient
      attention. METHODS: The Study of Health in Pomerania is a population-based survey
      in Germany that was conducted in a previously iodine-deficient region. A study
      population of 4087 subjects (2050 women) without overt hyperthyroidism or
      increased serum thyrotropin levels was available for the present study. Serum
      thyrotropin levels < 0.25 mIU/l and < 0.1 mIU/l were considered decreased and
      suppressed, respectively. RESULTS: Multivariable analyses revealed lower adjusted
      mean values for systolic blood pressure in subjects with decreased [132.9 mmHg,
      95% confidence interval (CI) = 131.1 mmHg; 134.8 mmHg] versus normal serum
      thyrotropin levels (135.0 mmHg, 95% CI = 134.4 mmHg; 135.6 mmHg, P = 0.04). The
      adjusted mean values for diastolic blood pressure and pulse pressure did not
      differ significantly between both groups. Analyses that were performed after all
      subjects receiving antihypertensive medications had been excluded did not reveal
      any statistically significant associations between decreased serum thyrotropin
      levels and the endpoints investigated. There was also no association of
      suppressed serum thyrotropin levels with blood pressure or hypertension.
      CONCLUSION: It is concluded that subclinical hyperthyroidism, as demonstrated by
      decreased as well as suppressed serum thyrotropin levels and serum free thyroid
      hormone levels within the reference range, is not associated with hypertension.

PMID- 16957554
TI  - Tissue kallikrein gene polymorphisms induce no change in endothelium-dependent or
      independent vasodilation in hypertensive and normotensive subjects.
AB  - BACKGROUND: Tissue kallikrein (TK) generates Lys-bradykinin, which is then
      converted to bradykinin and releases nitric oxide (NO) from endothelial cells via
      B2 receptors. TK gene inactivation in mice causes severe endothelial dysfunction,
      which is also a hallmark of human primary hypertension (PH). Healthy carriers of
      a loss-of-function Arg to His substitution at position 53 (R53H) of the TK gene
      exhibit paradoxical arterial eutrophic remodeling. We therefore investigated the
      impact of this and other TK gene single nucleotide polymorphisms (SNPs) on
      endothelium-dependent vasodilatation (EDV) and endothelium-independent
      vasodilatation (EIV) in PH patients and normotensive (NT) subjects. METHODS: The
      TK gene SNPs were genotyped blind to the phenotype by sequencing. We compared EDV
      and EIV vasodilatation across TK genotypes in 131 uncomplicated PH patients and
      51 healthy NT subjects. EDV and EIV were assessed as the forearm blood flow
      response to a graded infusion of acetylcholine and sodium nitroprusside,
      respectively. We also evaluated the impact of the SNPs on NO-mediated EDV and on
      reactive oxygen species (ROS)-induced NO breakdown with the nitric oxide synthase
      (NOS) inhibitor N(G)-monomethyl-L-arginine or vitamin C, respectively. RESULTS:
      Genotypes and allele frequencies were in Hardy-Weinberg equilibrium and similar
      in PH and NT. EDV was lower in PH patients than in NT subjects. No TK genotype
      affected either EDV or EIV per se, or via interaction with gender and age. NO
      inhibition and scavenging of ROS showed no TK genotype effect on EDV. Similar
      conclusions were obtained with haplotype analysis. CONCLUSIONS: These results do
      not support the contention that TK gene SNPs have a major impact in determining
      NO-mediated responses to acetylcholine.

PMID- 16957555
TI  - Association of a functional polymorphism in the CYP4A11 gene with systolic blood
      pressure in survivors of myocardial infarction.
AB  - OBJECTIVE: Survivors of myocardial infarction (MI) are known to have a high
      prevalence of arterial hypertension which, at the same time, imposes a major risk
      to such patients. Genetic variants of the arachidonic acid monooxygenase CYP4A11
      may result in decreased synthesis of 20-hydroxyeicostatetraenoic acid (20-HETE),
      experimental hypertension and elevated blood pressure levels in humans. The
      present study aimed to investigate the impact of the functionally relevant T8590C
      polymorphism of this gene on blood pressure and the prevalence of hypertension in
      MI patients. METHODS: Survivors of MI from the MONICA Augsburg MI registry (n =
      560) were studied after a mean of 5.6 years after the acute event. Participants
      were examined by standardized anthropometric and echocardiographic measurements,
      as well as genotyping for CYP4A11 T8590C allele status. RESULTS: Genotype
      frequencies in MI patients (TT = 71.8%, CT = 26.2%, CC = 2.0%) did not differ
      from those in population-based controls (n = 1363; TT = 75.4%, CT = 22.5% and CC
      = 2.1%, P = 0.22). MI survivors with the CC genotype displayed higher systolic
      blood pressure levels (CC: 143.4 +/- 4.9 mmHg versus CT: 134.5 +/- 1.3 mmHg and
      TT: 131.1 +/- 0.8 mmHg; P = 0.02) and a non-significant trend towards higher
      diastolic blood pressure levels (CC: 88.4 +/- 3.0 mmHg versus CT: 84.9 +/- 0.8
      mmHg and TT: 83.9 +/- 0.5 mmHg; P = 0.17) in multivariate models. Accordingly,
      the C allele was related to elevated odds ratios for hypertension in a recessive
      [4.14; 95% confidence interval (CI) = 1.07-15.96, P = 0.04] and in a dominant
      model (1.50; 95% CI = 1.03-2.20, P = 0.04), respectively. No blood pressure
      independent association of the T8590C polymorphism with echocardiographic
      parameters of left ventricular function and/or geometry was found. CONCLUSION:
      The data obtained in the present study strengthen the evidence of an association
      of the CYP4A11 T8590C polymorphism with blood pressure levels and hypertension
      prevalence. Particularly, the risk of arterial hypertension is substantially
      higher in MI patients homozygous for the CC allele. By contrast, no evidence was
      obtained for an association between this genotype and MI.

PMID- 16957556
TI  - The role of angiotensin(1-7) in renal vasculature of the rat.
AB  - OBJECTIVE: Angiotensin(1-7) is an active component of the renin-angiotensin
      aldosterone system. Its exact role in renal vascular function is unclear. We
      therefore studied the effects of angiotensin(1-7) on the renal vasculature in
      vitro and in vivo. METHODS: Isolated small renal arteries were studied in an
      arteriograph system by constructing concentration-response curves to angiotensin
      II, without and with angiotensin(1-7). In isolated perfused kidneys, the response
      of angiotensin II on renal vascular resistance was measured without and with
      angiotensin(1-7). The influence of angiotensin(1-7) on angiotensin II-induced
      glomerular afferent and efferent constriction was assessed with intravital
      microscopy in vivo under anaesthesia. In freely moving rats, we studied the
      effect of angiotensin(1-7) on angiotensin II-induced reduction of renal blood
      flow with an electromagnetic flow probe. RESULTS: Angiotensin(1-7) alone had no
      effect on the renal vasculature in any of the experiments. In vitro,
      angiotensin(1-7) antagonized angiotensin-II-induced constriction of isolated
      renal arteries (9.71 +/- 1.21 and 3.20 +/- 0.57%, for control and angiotensin(1
      7) pre-treated arteries, respectively; P < 0.0005). In isolated perfused kidneys,
      angiotensin(1-7) reduced the angiotensin II response (100 +/- 16.6 versus 72.6 +/
      15.6%, P < 0.05) and shifted the angiotensin II dose-response curve rightward
      (pEC50, 6.69 +/- 0.19 and 6.26 +/- 0.12 for control and angiotensin(1-7) pre
      treated kidneys, respectively; P < 0.05). Angiotensin(1-7), however, was devoid
      of effects on angiotensin-II-induced constriction of glomerular afferent and
      efferent arterioles and on angiotensin-II-induced renal blood flow reduction in
      freely moving rats in vivo. CONCLUSION: Angiotensin(1-7) antagonizes angiotensin
      II in renal vessels in vitro, but does not appear to have a major function in
      normal physiological regulation of renal vascular function in vivo.

PMID- 16957557
TI  - Can the blood pressure effects of COX-2 selective inhibitors be explained by
      changes in plasma aldosterone levels?
AB  - OBJECTIVE: The increased cardiovascular risk associated with rofecoxib may relate
      to differential effects on blood pressure (BP) in comparison with other
      cyclooxygenase-2 (COX-2) selective inhibitors. Rofecoxib is uniquely metabolized
      by cytosol reductase and may compete with aldosterone for metabolism. We
      hypothesized that the effect of rofecoxib on BP may be due to an increase in
      aldosterone levels. DESIGN: Prospective, randomized, cross-over study. SETTING:
      Tertiary institution. PATIENTS: Eleven patients (all female, age 65 +/- 11 years)
      with osteoarthritis and hypertension. INTERVENTIONS: Patients received rofecoxib
      50 mg once/day or celecoxib 400 mg once/day for 8 weeks, followed by cross-over
      after a 2-week wash-out period. OUTCOME MEASURES: Office BP, heart rate (HR),
      plasma aldosterone and aldosterone related-markers, markers of sympathetic and
      parasympathetic activity, catecholamines and heart rate variability (HRV) were
      measured. RESULTS: Rofecoxib caused an increase in BP compared to celecoxib; a
      change in recumbent systolic BP +/- SD (6.1 +/- 11.0 versus -7.0 +/- 12.5 mmHg, P
      < 0.05) and recumbent diastolic BP +/- SD (3.6 +/- 7.6 versus -1.7 +/- 5.7 mmHg).
      There was no difference in median change in plasma aldosterone levels between
      rofecoxib and celecoxib (-31 +/- 171.5 versus 43 +/- 147 pg/ml, P = 0.173). The
      other parameters measured were not different between the two agents. CONCLUSIONS:
      Rofecoxib therapy results in a significant increase in systolic BP compared to
      celecoxib. As plasma aldosterone levels were not different between the two drugs,
      the differential effect of rofecoxib on BP compared to celecoxib appears to be
      unlikely due to competition by rofecoxib for aldosterone metabolism.

PMID- 16957558
TI  - Elevation of plasma homocysteine by methionine loading increases the diastolic
      blood pressure response to exercise.
AB  - OBJECTIVE: Exercise blood pressure is elevated in conditions associated with
      endothelial dysfunction. To determine whether this is a causal association, we
      examined the effects of endothelial dysfunction induced by methionine loading, on
      exercise blood pressure. DESIGN: Healthy subjects (18-63 years) participated in
      randomized, double-blind, cross-over studies receiving methionine and placebo on
      separate occasions before exercise. METHODS: In study 1 (n = 32), subjects
      received placebo and methionine 100 mg/kg 4 h before exercise and, in study 2 (n
      = 11), placebo and methionine 200 mg/kg (given as 100 mg 20 and 12 h before
      exercise). A further study confirmed that methionine 100 mg/kg impaired brachial
      artery flow-mediated dilation. Blood pressure was measured by mercury
      sphygmomanometry at rest and during low workload bicycle ergometry. RESULTS:
      Plasma homocysteine increased after methionine compared to placebo (22.5 +/- 1.2
      versus 7.7 +/- 0.7 mumol/l in study 1, and 50.2 +/- 7.6 versus 12.8 +/- 0.7
      mumol/l in study 2, means +/- SE, each P < 0.0001). In both studies resting
      systolic and diastolic blood pressures and the increases in systolic blood
      pressure during exercise were similar after methionine and placebo. By contrast,
      exercise diastolic blood pressure responses (measured as the change from resting
      values) increased more after methionine than after placebo. In study 1, diastolic
      blood pressure responses increased relative to placebo by 3.5 +/- 1.0, 3.7 +/-
      1.0 and 2.4 +/- 1.0 mmHg at 50, 75 and 100 W, respectively (P < 0.01). In study
      2, diastolic blood pressure responses increased by 4.9 +/- 1.0, 5.4 +/- 2.1 and
      6.1 +/- 1.1 mmHg at 50, 75 and 100 W, respectively (P < 0.001). CONCLUSION:
      Endothelial dysfunction produced by methionine loading is associated with an
      increased exercise diastolic blood pressure response.

PMID- 16957559
TI  - Diguanosine pentaphosphate: an endogenous activator of Rho-kinase possibly
      involved in blood pressure regulation.
AB  - OBJECTIVE: Rho-kinase activity is increased in cardiovascular disease and in the
      pathophysiology of hypertension. Few endogenous factors are known that activate
      the Rho-kinase pathway. Stimulation of P2Y receptors activates the Rho-kinase
      pathway. Recently identified diguanosine pentaphosphate (Gp5G) possibly activates
      P2Y receptors. In this study, Gp5G was identified and quantified in human plasma.
      The influence of Gp5G on vascular tone was studied. METHODS: Gp5G in human plasma
      was purified to homogeneity by several steps. Gp5G was quantified and identified
      by matrix-assisted laser desorption/ionization mass spectrometry and enzymatic
      analysis. The vasoactive effects of Gp5G were studied in the isolated perfused
      rat kidney and after intra-aortic application. Activation of Rho-kinase was
      measured using western blot analysis. RESULTS: The plasma level of Gp5G in
      healthy donors is 9.47 +/- 4.97 nmol/l. Gp5G increases contractile responses
      induced by angiotensin II in a dose-dependent way [ED50 (-log mol) angiotensin
      II: 10.9 +/- 0.1; angiotensin II plus Gp5G (100 nmol/l): 11.5 +/- 0.1]. P2
      receptor antagonists inhibited the Gp5G-induced increase in angiotensin II
      vasoconstriction. MRS2179, a selective P2Y1 receptor antagonist, had no effect on
      Gp5G-mediated angiotensin II potentiation. Rho-kinase inhibition by Y27632
      abolished the Gp5G-induced increase of contractile responses to angiotensin II.
      Concentrations of 10 nmol/l Gp5G activated the translocation of RhoA from the
      cytosolic to the membranous fraction indicating the activation of Rho-kinase. The
      intra-aortic application of 100 pmol Gp5G significantly increased mean arterial
      blood pressure by 13.5 +/- 4.2 mmHg. CONCLUSION: Gp5G is an endogenous activator
      of Rho-kinase, which might affect vascular tone control by Rho-kinase at
      physiological levels. Gp5G activates P2Y4&6 receptors, and might play a role in
      physiological and pathophysiological vascular tone control.

PMID- 16957560
TI  - Blood pressure is the major driving force for plaque formation in aortic
      constricted ApoE-/- mice.
AB  - OBJECTIVE: Using an aortic constriction model in mice, we studied whether the
      increase in pressure or the activation of the renin-angiotensin system (RAS) and
      its main receptors is the main driving force for plaque progression. METHODS:
      Male ApoE mice underwent sham surgery or placement of a suprarenal silver clip
      around the aorta (AoC). Half the group was treated with the selective AT1
      receptor antagonist losartan (30 mg/kg per day) for 4 weeks. RESULTS:
      Anesthetized mean arterial pressure (MAP) was increased in AoC mice compared to
      sham (106 +/- 3 versus 90 +/- 1 mmHg, P < 0.001). Losartan reduced MAP in sham
      mice (78 +/- 2 mmHg, P < 0.01) but not in AoC (AoC losartan 104 +/- 2 mmHg).
      Plasma renin concentration (PRC) was increased in AoC mice compared to sham [1.6
      +/- 0.3 versus 0.8 +/- 0.2 milliGoldblatt units (mGU)/ml, P < 0.001]. Losartan
      treatment augmented this difference (18.7 +/- 3.7 versus 4.6 +/- 1.7 mGU/ml, P <
      0.01). AT2 receptor mRNA expression was increased 5.8-fold by aortic constriction
      in thoracic aorta (P < 0.05) and the major site for expression of the AT2
      receptor protein was within the plaques. The plaque area was increased in AoC
      mice compared to sham (0.61 +/- 0.09 versus 0.07 +/- 0.01%, P < 0.001); however,
      losartan did not alter plaque area. CONCLUSIONS: Our data do not support a role
      for the AT1 receptor in the progression of atherosclerosis in this model, since
      blockade with losartan did not alter plaque distribution. Furthermore, we found
      no support for the counteraction of atherogenesis by increased activity of the
      RAS acting on the AT2 receptor. Our data suggest that increased pressure is the
      main driving force for atherosclerosis in this model.

PMID- 16957561
TI  - Blood pressure categories, hypertensive subtypes, and the metabolic syndrome.
AB  - BACKGROUND: Elevated blood pressure (BP) is one element of metabolic syndrome
      (MetS); however, the relation of various BP categories and hypertension subtypes
      to the likelihood of having MetS is not well defined. METHODS: We determined the
      odds of MetS, defined by the National Cholesterol Education Program, in various
      BP categories from a cross-sectional study of 5968 individuals aged at least 18
      years and untreated for hypertension (weighted to 124.7 million) in the National
      Health and Nutrition Examination Survey, 1999-2002. Nonhypertensive BP categories
      were optimal, normal, and high-normal BP, according to JNC-VI classification.
      Hypertension consisted of three subtypes: isolated diastolic hypertension (IDH),
      systolic-diastolic hypertension (SDH), and isolated systolic hypertension (ISH).
      RESULTS: Among those with hypertension and MetS, 25.3% had IDH, 20.2% had SDH,
      and 54.5% had ISH. The MetS prevalence in nontreated persons was 5.8% for optimal
      BP, 9.1% for normal BP, 38.2% for high-normal BP, 45.9% for IDH, 44.3% for SDH,
      and 43.9% for ISH. Risk factor odds ratios (95% confidence intervals; reference
      group, optimal BP), adjusted for age, sex, total cholesterol, and smoking, were
      1.6 (1.2-2.2) for normal BP, 9.4 (6.9-12.7) for high-normal BP, 14.7 (8.9-24.0)
      for IDH, 12.2 (7.2-20.8) for SDH, and 10.2 (7.0-14.9) for ISH (all P < 0.01);
      odds ratios were higher for women in all categories. CONCLUSIONS: Despite having
      the lowest mean age, IDH subtype is associated with greatest likelihood of MetS.
      The high frequency of ISH in the hypertensive population, however, makes ISH the
      most common hypertensive subtype in persons with MetS.

PMID- 16957562
TI  - Type 2 diabetes mellitus is a risk factor for the development of hypertension in
      postmenopausal women.
AB  - OBJECTIVE: Hypertension and type 2 diabetes mellitus are common diseases that are
      frequently found concomitantly in postmenopausal women. These findings suggest a
      close and/or synergistic nature in the relationship between the two disease
      processes; however, no prospective data exist on the incidence rate of
      hypertension in postmenopausal women with type 2 diabetes mellitus. METHODS: The
      present study assessed the risk of developing hypertension in 840 postmenopausal
      women: 102 women (12.1% of the cohort) with type 2 diabetes mellitus and 738
      (87.9%) free of diabetes. The mean +/- SD follow-up was 3.2 +/- 0.9 years (range
      0.5-6.0 years). RESULTS: The incidence rate (cases of hypertension per 100 person
      years) was 1.1 for the group of women without diabetes versus 5.6 in women with
      diabetes (P < 0.0001). Compared with the non-diabetic group, women with type 2
      diabetes mellitus had a statistically significant higher risk of developing
      hypertension. The relative risks for women with diabetes was 5.09 [crude: 95%
      confidence interval (CI) = 3.52-7.36; P < 0.0001]; 3.43 (adjusted for body mass
      index and waist circumference: 95% CI = 2.25-5.14; P < 0.001); and 2.95 (adjusted
      for all potential confounders: 95% CI = 1.86-4.32; P < 0.01). CONCLUSION: In our
      prospective study, on the incidence of hypertension, the presence of type 2
      diabetes was found to be a potent independent risk determinant. This suggests
      that postmenopausal women affected by type 2 diabetes mellitus comprise a
      population at high risk for the subsequent development of hypertension.

PMID- 16957563
TI  - The calcium-channel blocker, azelnidipine, enhances the inhibitory action of AT1
      receptor blockade on ischemic brain damage.
AB  - OBJECTIVE: The combined effects of a calcium-channel blocker (CCB) with an
      angiotensin (Ang) II type 1 (AT1) receptor blocker were investigated in focal
      brain ischemia induced by middle cerebral artery (MCA) occlusion. METHODS AND
      RESULTS: In male C57BL/6J mice, permanent occlusion of the MCA-induced focal
      cerebral ischemia and neurological deficit after 24 h, accompanied by a reduction
      of cerebral blood flow and an increase in superoxide production in the ischemic
      area. Administration of azelnidipine, a CCB, at 1.0 mg/kg per day for 10 days
      significantly suppressed these changes after MCA without affecting systolic blood
      pressure. Such inhibitory effects of azelnidipine on brain ischemia could be
      observed in AT1a receptor-deficient mice. In addition, olmesartan, an AT1
      receptor blocker, at 3.0 mg/kg per day also diminished the ischemic brain area
      and neurological score, as well as superoxide production and the reduction of
      cerebral surface blood flow in C57BL/6 mice. The combination of lower doses of
      azelnidipine (0.1 mg/kg per day) and olmesartan (0.5 mg/kg per day) significantly
      attenuated the ischemic brain area, neurological score, superoxide production and
      the reduction of cerebral surface blood flow after MCA occlusion in C57BL/6 mice,
      whereas either of these agents alone at these doses did not affect brain
      ischemia. CONCLUSION: These results indicate that azelnidipine inhibited ischemic
      brain damage induced by MCA occlusion, at least in part, through suppression of
      blood flow change and oxidative stress via a signaling mechanism independent of
      AT1 receptor stimulation. Moreover, azelnidipine synergistically enhanced the
      inhibitory action of olmesartan on brain ischemia, suggesting beneficial combined
      effects of a CCB with an AT1 receptor blocker on ischemic brain damage.

PMID- 16957564
TI  - Ambulatory arterial stiffness index and renal abnormalities in primary
      hypertension.
AB  - OBJECTIVE: Arterial stiffness is a predictor of cardiovascular mortality in the
      general population as well as in hypertension and end-stage renal disease. We
      investigated the relationship between a recently proposed ambulatory blood
      pressure monitoring-derived index of arterial stiffness and early signs of renal
      damage in patients with primary hypertension. DESIGN AND SETTING: A total of 168
      untreated patients with sustained primary hypertension were studied. Ambulatory
      arterial stiffness index (AASI) was calculated based on 24-h ambulatory blood
      pressure readings. Albuminuria was measured as the albumin to creatinine ratio.
      Creatinine clearance was estimated using the Cockcroft-Gault formula, and the
      interlobar resistive index was evaluated by renal ultrasound and Doppler
      examination. RESULTS: AASI was positively related to urinary albumin excretion
      and resistive index, and was negatively related to estimated creatinine clearance
      and renal volume to the resistive index ratio. Patients with AASI above the
      median (i.e. > 0.51) showed a higher prevalence of microalbuminuria and a mild
      reduction in creatinine clearance. Moreover, patients with microalbuminuria or a
      mild reduction in creatinine clearance had significantly higher AASI values
      compared with those without, and the greater the renal involvement, the greater
      the AASI. After adjusting for several potentially confounding variables, we found
      that each standard deviation increase in AASI (i.e. 0.16) entails an almost
      twofold greater risk of renal involvement. CONCLUSION: Increased AASI is
      independently associated with early signs of renal damage in patients with
      sustained primary hypertension. These results strengthen the usefulness of AASI
      and ambulatory blood pressure monitoring in cardiovascular risk assessment.

PMID- 16957565
TI  - Low triiodothyronine and cardiomyopathy in patients with end-stage renal disease.
AB  - OBJECTIVES AND METHODS: Low free plasma triiodothyronine (fT3) is associated with
      inflammation and cardiovascular damage in patients with end-stage renal disease
      (ESRD). We investigated the relationship between fT3, left ventricular systolic
      function and left ventricular mass in a group of 234 dialysis patients, and
      modelled the association between fT3 and cardiomyopathy in statistical analyses
      including both direct (interleukin-6 and C-reactive protein) and inverse (serum
      albumin) acute phase inflammation markers. RESULTS: Plasma fT3 concentration in
      dialysis patients was significantly (P < 0.001) reduced in comparison with
      healthy participants and clinically euthyroid patients with normal renal
      function. Left ventricular systolic function was depressed (P <or= 0.003) and
      left ventricular mass increased (P < 0.001) in patients in the first fT3 quartile
      as compared with patients in other quartiles. In multiple regression analyses
      these associations remained significant also after adjustment for Framingham risk
      factors and antihypertensive therapy (P </= 0.01), and for risk factors peculiar
      to ESRD (P = 0.03). Adjustments for interleukin-6 or for albumin, however,
      abrogated these relationships. CONCLUSIONS: Low triiodothyronine is associated
      with left ventricular dysfunction and left ventricular hypertrophy in ESRD
      patients. These associations appear largely mediated by inflammation. Low fT3 may
      be an intermediate mechanism implicated in the adverse cardiac effects of
      inflammation in patients with ESRD.

PMID- 16957566
TI  - Rosiglitazone reduces microalbuminuria and blood pressure independently of
      glycemia in type 2 diabetes patients with microalbuminuria.
AB  - OBJECTIVE: To test the hypothesis that rosiglitazone combined with metformin
      provides a greater reduction in microalbuminuria and blood pressure than
      metformin and glyburide at comparable levels of glycemic control. METHODS: In a
      double-blind, parallel-group design 389 participants with type 2 diabetes were
      followed for 32 weeks. RESULTS: Urinary albumin: creatinine ratio was
      significantly reduced at 32 weeks compared with baseline in the rosiglitazone
      plus metformin group (-22.7%; P < 0.01) but not in the glyburide plus metformin
      comparator group (-7.1%; P = 0.32). Patients who completed the study (81.5%)
      demonstrated a treatment difference of -19.5% (P = 0.03), favoring the
      rosiglitazone group. Rosiglitazone plus metformin reduced both mean 24-h systolic
      (-3.4 mmHg; P = 0.01) and diastolic (-2.5 mmHg; P < 0.01) ambulatory blood
      pressure compared with glyburide plus metformin. Addition of rosiglitazone to
      metformin also reduced levels of plasminogen activator inhibitor-1 antigen and
      activity, C-reactive protein, von Willebrand factor and fibrinogen compared with
      addition of glyburide. CONCLUSIONS: Rosiglitazone added to background therapy
      with metformin provides greater reductions in microalbuminuria and blood pressure
      as compared with glyburide. These additional improvements in microalbuminuria,
      blood pressure and cardiovascular biomarkers were observed despite comparable
      improvements in glycemic control in both groups and may be related to the anti
      inflammatory properties of rosiglitazone.

PMID- 16957567
TI  - Enhancement of cardiac oxidative stress by tachycardia and its critical role in
      cardiac hypertrophy and fibrosis.
AB  - OBJECTIVE: To examine the mechanism and significance of tachycardia-induced
      cardiac damage, using azelnidipine, a relatively new dihydropyridine calcium
      channel blocker which does not increase heart rate. METHODS: Comparing
      azelnidipine and amlodipine, we examined the cardiac effects and the direct
      effects on a sinus node/atrial preparation in stroke-prone spontaneously
      hypertensive rats (spSHRs). By pacing the right atrium, we examined the effect of
      tachycardia per se on cardiac oxidative stress. Using apocynin, a reduced
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, we
      investigated the role of oxidative stress in cardiac remodelling. RESULTS:
      Azelnidipine suppressed cardiac hypertrophy, fibrosis, NADPH oxidase and
      superoxide in spSHRs more potently than amlodipine, and was associated with lower
      heart rates than amlodipine. Azelnidipine caused a greater reduction than
      amlodipine in the beat rate of the sinus node/atrial preparation of spSHRs. A 10
      or 20% increase in heart rate, independent of blood pressure or sympathetic nerve
      activity, significantly enhanced cardiac NADPH oxidase activity, superoxide and
      activated mitogen-activated protein kinases. Reduction of cardiac oxidative
      stress by apocynin led to the suppression of cardiac hypertrophy, inflammation
      and fibrosis in spSHRs, beyond its hypotensive effect. CONCLUSIONS: Our work
      provided evidence that the increase in heart rate per se, independent of
      sympathetic nerve activity, enhances cardiac oxidative stress and activates
      mitogen-activated protein kinases, which seem to be responsible for cardiac
      remodelling. Azelnidipine, without causing an increase in heart rate, has the
      potential to be useful for the treatment of cardiac remodelling.

PMID- 16957568
TI  - Impact of the time rate of blood pressure variation on left ventricular mass.
AB  - OBJECTIVES: Blood pressure (BP) changes are steeper in hypertensive than in
      normotensive individuals, whereas an increased rate of BP fluctuations is
      associated with medial hypertrophy of the carotid arteries. We evaluated the
      association between the rate of BP variation derived from ambulatory blood
      pressure monitoring (ABPM) data analysis and left ventricular mass (LVM).
      METHODS: ABPM and echocardiographic measurements of LVM were performed in 365
      normotensive, 185 white-coat hypertensive (WCH) and 448 uncomplicated
      hypertensive individuals. RESULTS: The daytime and night-time rate of systolic
      blood pressure (SBP) and diastolic BP variation were significantly higher in
      hypertensive than in normotensive (P < 0.001) and WCH (P < 0.05) individuals. In
      the entire study population multiple linear regression models revealed
      independent determinants of LVM in the following rank order: body mass index
      (beta + 0.266, P < 0.001), daytime SBP (beta + 0.264, P < 0.001), male sex (beta
      +0.220, P < 0.001), age (beta + 0.203, P < 0.001), daytime heart rate (HR; beta -
      0.191, P < 0.001), daytime rate of SBP variation (beta + 0.167, P < 0.001), and
      SBP dipping (beta - 0.132, P < 0.001). A 0.1 mmHg/min increase in the daytime
      rate of SBP variation correlated with an increment of 7.087 g (95% confidence
      interval 4.775-9.399) in the LVM. The addition of the daytime rate of SBP
      variation in the multiple regression model for the prediction of LVM
      significantly increased the adjusted model R [R change 0.024 (2.4%); P for change
      < 0.001]. CONCLUSION: Steeper BP variations may produce a greater stress on the
      left ventricular wall and may have an additive role to body habitus, BP and HR
      levels in the detection of cardiac hypertrophy. Target-organ damage in
      hypertensive patients, in addition to BP levels, dipping status and BP
      variability, may also be related to a steeper rate of BP oscillations.

PMID- 16957569
TI  - Electrocardiographic strain pattern and left ventricular diastolic function in
      hypertensive patients with left ventricular hypertrophy: the LIFE study.
AB  - BACKGROUND: Whether the typical electrocardiographic (ECG) strain pattern
      (Strain, in leads V5 and/or V6), which is associated with left ventricular
      hypertrophy (LVH) and LV systolic dysfunction, is independently associated with
      LV diastolic dysfunction is unknown. METHODS: The Losartan Intervention For
      Endpoint reduction in hypertension (LIFE) study enrolled hypertensive patients
      with ECG-LVH, of whom 10% underwent Doppler echocardiography. LV diastolic
      function measures included peak mitral E and A wave velocities and their ratio
      (E/A); E wave deceleration time (EDT); atrial filling fraction (AFF); and
      isovolumic relaxation time (IVRT). Normal filling pattern was defined by E/A < 1
      with EDT >or= 150 and <or= 250 ms and IVRT <or= 100 and >or=60 ms; abnormal
      relaxation by E/A < 1 with EDT > 250 ms or IVRT > 100 ms; pseudonormal filling
      pattern by E/A >or= 1 associated with IVRT > 100 ms or EDT > 250 ms; restrictive
      pattern by E/A >or= 1 with IVRT < 100 ms and EDT < 250 ms. A combined index of LV
      systolic-diastolic function was also computed (isovolumic time/ejection time,
      modified myocardial performance index). Of LIFE echo substudy participants with
      all needed ECG and Doppler data (n = 791), 110 (14%) had Strain. RESULTS: Strain
      was associated with male gender, African-American race, diabetes, history of
      coronary heart disease (CHD), higher systolic blood pressure (BP), LV mass and
      relative wall thickness, and higher prevalences of echo-LV hypertrophy and wall
      motion abnormalities, and with slower heart rate (all P < 0.05). Age, diastolic
      BP and LV ejection fraction were similar in patients with or without Strain.
      Diastolic parameters, and prevalences of different LV filling patterns, did not
      differ significantly between patients with versus those without Strain (all P >
      0.1), but modified myocardial performance index was higher with Strain (P <
      0.05). Findings were consistent in multivariate analyses. The association of
      Strain with higher modified myocardial performance index was no longer
      statistically significant after accounting for LV systolic function and wall
      motion abnormalities. CONCLUSIONS: In hypertensive patients with ECG-LVH, the ECG
      Strain pattern did not identify independently those with more severe LV diastolic
      abnormalities.

PMID- 16957570
TI  - Pulse wave velocity is increased in patients with transient myocardial ischemia.
AB  - OBJECTIVE: We have recently shown that mean pulse pressure is higher in patients
      with transient myocardial ischemia. Pulse pressure elevation might be an
      important consequence of increased arterial stiffness. The aim of this study was
      to prove if arterial stiffness is changed in patients with transient myocardial
      ischemia who bear a high cardiovascular risk. Additionally we investigated
      whether arterial stiffness or wave reflection is the best indicator for transient
      myocardial ischemia. Aortic pulse wave velocity (PWV) is a measure of arterial
      stiffness, and augmentation index (AIx) an indication of arterial wave
      reflection. Both are indicators for cardiovascular risk. METHODS: PWV (carotid
      femoral) and AIx (SphygmoCor) were assessed in 74 hypertensive patients.
      Transient myocardial ischemia was detected using an ST-triggered 24-h ambulatory
      blood pressure monitoring device. RESULTS: ST-segment depressions were recorded
      in 30 of 74 patients. There were no significant differences with regard to age,
      mean arterial pressure, systolic blood pressure, diastolic blood pressure or
      heart rate. PWV was seen to be higher in patients with transient myocardial
      ischemia (10.6 versus 9.5 m/s, P = 0.036). There was no significant difference in
      AIx between the two groups. PWV (r = 0.36, P = 0.002) but not AIx correlated with
      pulse pressure. CONCLUSIONS: PWV is higher in hypertensive individuals (age > 60
      years) with transient myocardial ischemia, suggesting that PWV is an indicator of
      increased cardiovascular risk. Although AIx is known to be associated with
      several cardiovascular diseases, it was not seen to be associated with silent
      myocardial ischemia. Our results suggest that the clinical significance of
      parameters of arterial stiffness and arterial wave reflection change with age,
      with a higher clinical importance of PWV indicated in patients over the age of
      60.

PMID- 16957571
TI  - Falls in blood pressure in patients with obstructive sleep apnoea after long-term
      nasal continuous positive airway pressure treatment.
AB  - OBJECTIVES: Effective treatment of obstructive sleep apnoea (OSA) with nasal
      continuous positive airway pressure (nCPAP) lowers blood pressure (BP). The long
      term effects of nCPAP treatment on BP in OSA patients are not well known. The
      time period of such treatment sufficient to lower BP in OSA patients is also not
      known. We investigated compliance with long-term nCPAP therapy and its effects on
      BP. METHODS: This observational study involved 66 OSA patients [59 men, seven
      women; mean age, 51 (48-54) years; body mass index (BMI), 28.7 (27.7-29.7) kg/m;
      apnoea and hypopnoea, 50.3 (45.6-55.0)/h; 95% confidence intervals]. BP and BMI
      were measured before the study and at two checkpoints after usage of nCPAP [620
      (552-688) and 1071 (1000-1143) days]. RESULTS: The different times between the
      first and second checkpoints for detecting objective compliance were 17 (4-30)
      min (P = 0.003). Diastolic BP decreased by 5.9 (3.1-8.7) mmHg after 600 days
      nCPAP treatment and by 4.6 (2.0-7.2) mmHg after 1000 days (P = 0.0006). Systolic
      BP and BMI did not change significantly. Usage of nCPAP treatment for a daily
      average of 3 h was needed to achieve a significant decrease in diastolic BP [7.4
      (4.3-10.6) mmHg, P < 0.0001]. Diastolic BP of normotensive OSA patients did not
      change significantly by nCPAP treatment, but that of hypertensive OSA patients
      decreased significantly within 1 month-3 years of nCPAP treatment whether or not
      medication was used. CONCLUSIONS: In patients with severe OSA, the use of nCPAP
      for a daily average of 3 h would be sufficient to decrease the diastolic BP of
      hypertensive OSA patients.

PMID- 16957572
TI  - Relationship between antihypertensive drug therapy and cognitive function in
      elderly hypertensive patients with memory complaints.
AB  - OBJECTIVE: To evaluate the relationship between antihypertensive treatments and
      cognitive function in elderly hypertensive patients with memory complaints.
      METHODS: The association between cognitive function and antihypertensive drug
      therapy was studied in 1241 hypertensive elderly patients with memory complaints
      attending a geriatric outpatient clinic. Cognitive function was assessed using
      the Mini Mental State Examination (MMSE) and validated neuropsychological tests
      (Cognitive Efficiency Profile; CEP). Patients were classified into four
      categories according to their cognitive status: normal cognitive function, mild
      cognitive impairment (MCI), Alzheimer's disease (AD) or vascular dementia (VaD).
      RESULTS: In this population aged 78 +/- 8 years, with a mean blood pressure of
      152 +/- 19/86 +/- 12 mmHg, antihypertensive treatment was prescribed for 57% of
      patients. After adjustment for age, sex and education, treated hypertensive
      patients had better cognitive function than untreated patients (MMSE score 23.9
      +/- 5.6/30 versus 22.7 +/- 6.4/30, P < 0.001, CEP score 49.1 +/- 24.9/100 versus
      45.4 +/- 23.7/100, P < 0.001). This association was observed independently of the
      cognitive status, both in normal, MCI, AD and VaD hypertensive patients. The odds
      ratio (OR) for AD was 0.58 [95% confidence interval (CI) 0.42-0.81] in treated
      compared with untreated hypertensive patients. In patients on antihypertensive
      therapy, higher cognitive function was observed in patients using calcium
      antagonists compared with those without calcium antagonists (CEP 52.9 +/-
      24.6/100 versus 46.4 +/- 23.4/100, P < 0.001; OR for AD 0.67; 95% CI 0.45-0.99),
      independently of blood pressure level. CONCLUSIONS: Antihypertensive therapy was
      associated with a lower risk of cognitive impairment and AD. In particular, the
      use of calcium antagonists was associated with a decreased risk of cognitive
      impairment and AD independently of the blood pressure level, suggesting a
      specific neuroprotective effect of these antihypertensive agents.

PMID- 16957573
TI  - Effect of candesartan on coronary flow reserve in patients with systemic
      hypertension.
AB  - BACKGROUND: Patients with hypertension have structural and functional changes in
      conductance and resistance vessels. In the absence of coronary stenosis the
      coronary microvascular function can be analysed by studying the coronary reserve.
      The aim of this study was to evaluate, non-invasively, the effect of candesartan
      on coronary microvascular function in hypertensive patients. METHODS: Twenty-two
      hypertensive patients (> 40 years) without clinical coronary disease (age 63.86
      +/- 10.3 years; women, 59.1%) were studied. In addition to blood pressure (BP),
      measurement of carotid intima-medial thickness (IMT), left ventricle mass index
      (LVMI) and the coronary flow reserve (CFR) were evaluated with echography at the
      beginning, and after 3 months of treatment with 16 mg/day of candesartan. Twelve
      hypertensive controls (64.50 +/- 10.8 years; women, 58.4%) completed the same
      study without any change in treatment. RESULTS: A 15% improvement in CFR (3.10 +/
      1.02 to 3.56 +/- 1.06; P = 0.001) was observed simultaneously with the BP
      reduction. There was no change in CFR in the control group (2.9 +/- 1.1 to 3.01
      +/- 0.9; P = 0.23). The IMT was not modified significantly at the end of the
      follow-up (0.86 +/- 0.1 to 0.83 +/- 0.1 mm; P = 0.103). CONCLUSION: Candesartan
      improves the CFR in hypertensive patients. The improvement was not related to BP
      control or LVMI regression. Patients with a lower CFR show a better response to
      candesartan. This fact can be demonstrated non-invasively with echography after 3
      months of therapy.

PMID- 16957574
TI  - Lifestyle interventions to reduce raised blood pressure.

PMID- 16957575
TI  - C-reactive protein and cardiovascular disease: are we looking in the right
      direction?

PMID- 16957577
TI  - Proteomics in diagnostic neuropathology.
AB  - In the "postgenome" era, attention has turned to the proteome as a source of
      complementary diagnostic and prognostic information. Recent advances in imaging
      mass spectrometry (IMS) uses matrix-assisted laser desorption ionization-mass
      spectrometry (MALDI-MS) to acquire up to 1,000 individual protein signals within
      the molecular weight range of 2,000 to over 100,000 in specific areas of tissue
      sections. The systematic investigation of these sections permits creation of
      specific molecular weight images (ion density maps) for each signal detected.
      Analysis of these images can reveal a collection of unique protein changes, or a
      "protein signature", of diagnostic and prognostic value. These signatures may
      also afford assessment of disease progression and tissue response to treatments.
      Combined with histology and molecular genetic analyses, new proteomic techniques
      should refine subclassifications and provide defining information about the
      pathogenesis of many central and peripheral nervous system diseases.

PMID- 16957578
TI  - Correlation among pathology, genotype, and patient outcomes in glioblastoma.
AB  - Glioblastomas are histologically and genetically heterogeneous. We have
      investigated to what extent histologic features reflect the genetic profile and
      whether they are predictive of clinical outcome. Key histologic characteristics,
      including major cell types (small cell, nonsmall cell), other components such as
      oligodendroglial components, gemistocytes, multinucleated giant cells, as well as
      necrosis and microvascular proliferation, of 420 cases of glioblastoma within a
      population-based study (1) were reassessed and correlated with patients' clinical
      outcome and key genetic alterations. EGFR amplification and p16 homozygous
      deletion were significantly more frequent in small cell glioblastomas than in
      nonsmall cell glioblastomas (EGFR, 46% vs 26%, p = 0.0002; p16 39% vs 25%, p =
      0.0167). Multivariate analyses with adjustment for age and gender showed that
      small cell glioblastomas had frequent EGFR amplification and p16 deletion but
      infrequent PTEN mutations. An oligodendroglial component was detected in 20% of
      glioblastomas; these patients were significantly younger (54.4 +/- 13.6 vs 59.2
      +/- 13.8 years; p = 0.0049) and survived longer (10.3 +/- 8.3 vs 8.2 +/- 8.4
      months; p = 0.0647). However, multivariate analyses with adjustment for age and
      gender did not show the presence of an oligodendroglial component to be
      predictive of longer survival. After adjustment for age and gender, LOH 1p was
      associated with longer survival (hazard ratio, 0.7; 95% confidence interval [CI],
      0.5-1.0), whereas LOH 10q was associated with shorter survival (hazard ratio,
      1.4; 95% CI, 1.0-1.8) of patients with glioblastoma. Glioblastomas containing
      >or=5% multinucleated giant cells showed more frequent TP53 mutation and
      infrequent EGFR amplification than those containing <5% multinucleated giant
      cells (TP53, 45% vs 24%, p = 0.0001; EGFR, 24% vs 42%, p = 0.0005). Vascular
      proliferation was observed in all glioblastomas, whereas large ischemic and/or
      pseudopalisading necrosis was observed in 366 of 420 (87%) cases. Glioblastomas
      with necrosis were associated with older age (59.2 +/- 13.3 vs 51.6 +/- 15.3
      years; p = 0.0001) and shorter survival (7.9 +/- 6.8 vs 12.9 +/- 14.2 months; p =
      0.0017). Multivariate analyses with adjustment for age and gender confirmed this
      observation (hazard ratio, 1.5; 95% CI, 1.1-2.0). Multivariate analysis with
      adjustment for age and gender showed that necrosis was significantly associated
      with wild-type TP53 and absence of an oligodendroglial component. These results
      suggest that some histologic features in glioblastomas are associated with
      specific genetic alterations and with clinical outcome.

PMID- 16957579
TI  - Dysferlin is a new marker for leaky brain blood vessels in multiple sclerosis.
AB  - Dysferlin is a muscle protein involved in cell membrane repair and its deficiency
      is associated with muscular dystrophy. We describe that dysferlin is also
      expressed in leaky endothelial cells. In the normal central nervous system (CNS),
      dysferlin is only present in endothelial cells of circumventricular organs. In
      the inflamed CNS of patients with multiple sclerosis (MS) or in animals with
      experimental autoimmune encephalomyelitis, dysferlin reactivity is induced in
      endothelial cells and the expression is associated with vascular leakage of serum
      proteins. In MS, dysferlin expression in endothelial cells is not restricted to
      vessels with inflammatory cuffs but is also present in noninflamed vessels. In
      addition, many blood vessels with perivascular inflammatory infiltrates lack
      dysferlin expression in inactive lesions or in the normal-appearing white matter.
      In vitro, dysferlin can be induced in endothelial cells by stimulation with tumor
      necrosis factor-alpha. Hence, dysferlin is not only a marker for leaky brain
      vessels, but also reveals dissociation of perivascular inflammatory infiltrates
      and blood-brain barrier disturbance in multiple sclerosis.

PMID- 16957581
TI  - Evidence of apoptosis in the subventricular zone and rostral migratory stream in
      the MPTP mouse model of Parkinson disease.
AB  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is commonly used to create
      animal models of Parkinson disease. There is conflicting evidence on the
      occurrence of apoptosis induced by MPTP in the mouse substantia nigra pars
      compacta. We demonstrated that a single acute injection of MPTP induced apoptosis
      in the subventricular zone (SVZ) and rostral migratory stream (RMS) in the adult
      C57BL/6 mouse brain. The number of TUNEL-positive cells peaked at 24 hours after
      injection and decreased thereafter, paralleling the change in the number of
      cleaved caspase-3-positive cells after MPTP injection. Results of
      immunohistochemistry and ultrastructural analyses indicated that the majority of
      apoptotic cells in the SVZ and RMS were migrating neuroblasts (type A cells),
      whereas a few were astrocytes (type B cells). No apoptosis occurred in transit
      amplifying progenitors (type C cells). The decrease in A cell numbers was most
      marked on day 2 and lasted to day 8 after the administration. A rapid and
      transient phagocytosis of apoptotic cells by microglial cells was demonstrated to
      parallel the MPTP-induced apoptosis. The present findings provide new insight
      into the extensive neurotoxicity of MPTP and may be valuable in reevaluating the
      MPTP mouse model of Parkinson disease.

PMID- 16957580
TI  - LR11/SorLA expression is reduced in sporadic Alzheimer disease but not in
      familial Alzheimer disease.
AB  - LR11 is an ApoE receptor that is enriched in the brain. We have shown that LR11
      is markedly downregulated in patients with sporadic Alzheimer disease (AD). This
      finding led us to explore whether reduced LR11 expression reflects a primary
      mechanism of disease or merely a secondary consequence of other AD-associated
      changes. Therefore, LR11 expression was assessed in a transgenic mouse model of
      AD and familial AD (FAD) brains. Immunohistochemistry and immunoblotting of LR11
      in PS1/APP transgenic and wild-type mice indicated that LR11 levels are not
      affected by genotype or accumulation of amyloid pathology. LR11 expression was
      also evaluated based on immunoblotting and LR11 immunostaining intensity in human
      frontal cortex in controls, sporadic AD, and FAD, including cases with presenilin
      1 (PS1) and presenilin-2 (PS2) mutations. Although LR11 was reduced in sporadic
      AD, there was no difference in protein level or staining intensity between
      control and FAD cases. The finding that LR11 expression is unaffected in both a
      mouse model of AD and autosomal-dominant forms of AD suggests that LR11 is not
      regulated by amyloid accumulation or other AD neuropathologic changes. We
      hypothesize that LR11 loss may be specific to sporadic AD and influence amyloid
      pathology through mechanisms independent of substrate-enzyme interactions
      regulated by FAD mutations.

PMID- 16957582
TI  - NMDA receptor composition differs among anatomically diverse malformations of
      cortical development.
AB  - Altered excitatory synaptic activity is likely a key factor in the neuronal
      hyperexcitability of developmental cerebral malformations. Using a combined
      morphologic and molecular approach, we investigated the NMDA receptor and related
      protein composition in human epileptic patients affected by periventricular
      nodular heterotopia, subcortical band heterotopia, or focal cortical dysplasia.
      Our results indicate that expression levels of specific NMDA receptor subunits
      are altered in both cerebral heterotopia and cortical dysplasia. A selective
      increase in the NR2B subunit was present in all cortical dysplasia, whereas the
      expression level of NR2A and NR2B subunits was significantly downregulated in all
      patients with heterotopia. NR2B upregulation in cortical dysplasia was greater in
      the total homogenate than the postsynaptic membrane fraction, suggesting that
      mechanisms other than increased ionic influx through the postsynaptic membrane
      may sustain hyperexcitability in dysplastic neurons. In cerebral heterotopia, the
      NR2A and NR2B downregulation was accompanied by less evident reduction of the
      SAP97 and PSD-95 proteins of the MAGUK family, thus suggesting that NMDA
      impairment was associated with altered molecular structure of the postsynaptic
      membrane. Our results demonstrate that diverse human developmental malformations
      are associated with different alterations of the NMDA receptor, which may
      contribute to the genesis of epileptic phenomena.

PMID- 16957583
TI  - Lipid peroxidation during human cerebral myelination.
AB  - The critical period of human cerebral myelination is characterized by rapid
      production of cellular membranes. We hypothesize that this period is subject to
      the "physiological" generation of free radicals resulting in lipid peroxidation
      (LPO). In this study, oxidative markers were examined in developing human
      parietal white matter using 4-hydroxy-2-nonenal (HNE) protein adducts as an
      indicator of LPO. Immunocytochemistry showed an increase in HNE-positive glia
      from 40 gestational weeks to 1.5 postnatal years encompassing the peak period of
      myelin sheath synthesis at this site. Western blots showed a distinct pattern of
      HNE-modified proteins at fetal/term ages 26 to 42 gestational weeks and a second,
      different pattern at 45 gestational weeks to 2.5 postnatal years. Proteins
      modified by HNE in the latter period, corresponding to active myelination, were
      identified using mass spectrometry. The most prominent category of HNE
      modification included cytoskeletal proteins such as tubulins and neurofilaments.
      Other categories included cell type-specific proteins for mature oligodendrocytes
      and astrocytes and proteins involved in cell cycle and energy metabolism. We
      conclude that human brain development involves basal levels of oxidative stress
      and resulting LPO and that these processes target different proteins in an age
      specific manner, thereby likely playing distinct roles during different periods
      of brain maturation.

PMID- 16957584
TI  - Apoptosis and proliferation markers in diffusely infiltrating astrocytomas:
      profiling of 17 molecules.
AB  - Caspases and inhibitor of apoptosis proteins (IAPs) are antagonizing key
      apoptosis regulators. Limited studies of a few IAPs indicated their roles in
      astrocytomas. However, the overall expression status and significance of
      apoptosis regulators in astrocytomas is not clear. We examined the expression
      profile of the caspases (CASP3, 6, 7, 8, 9, 10, and 14), APAF1, SMAC, BCL2, the
      IAPs (BIRC5/survivin, CIAP1, CIAP2, XIAP, and LIVIN), and the proliferation
      markers Ki67 and PHH3 in 78 diffusely infiltrating astrocytomas and 24 normal
      brain samples by immunohistochemistry. Western blotting for major caspases and
      IAPs and reverse transcription-polymerase chain reaction analyses for IAPs were
      performed on a subset of 27 fresh samples. Our data showed BIRC5 nuclear labeling
      index (BIRC5-N) was the apoptosis marker most significantly different in World
      Health Organization grade II to IV astrocytomas and most strongly associated with
      proliferative activity. Expression level of other apoptosis-related proteins was
      modest or low in astrocytomas and did not correlate significantly with tumor
      grade or proliferation. Apoptosis regulators and proliferation markers were not
      detected in astrocytes of normal brain by immunostaining. This expression profile
      suggested involvement of apoptosis regulators in astrocytoma tumorigenesis, but
      tumor progression was more closely associated with proliferative advantages of
      which BIRC5 nuclear expression appeared to be a manifestation.

PMID- 16957587
TI  - Re: Powers JM. p53-Mediated apoptosis, neuroglobin overexpression, and globin
      deposits in a patient with hereditary ferritinopathy. J Neuropathol Exp Neurol
      2006;65:716-21.

PMID- 16957585
TI  - Leukemia inhibitory factor arrests oligodendrocyte death and demyelination in
      spinal cord injury.
AB  - As a consequence of secondary pathophysiological mechanisms elicited after spinal
      cord injury (SCI), oligodendrocytes die by waves of apoptosis. This ultimately
      results in demyelination of intact axons leading to a loss of their conducting
      properties. Preservation of as few as 5% to 10% of myelinated axons in individual
      tracts can confer locomotor recovery. Thus, strategies aimed at rescuing mature
      oligodendrocytes ensheathing viable axons are likely to be of therapeutic
      significance. We report that leukemia inhibitory factor (LIF) can prevent
      oligodendrocyte apoptosis, notably contralateral to the spinal cord lesion,
      through the induction of the JAK/STAT and Akt signaling pathways as well as by
      potentiating the expression of the antiapoptotic molecule, cIAP2. Reduced
      oligodendrocyte apoptosis after SCI with LIF administration resulted in a
      substantial decrease in demyelination shown by the preservation of lamellated
      myelin surrounding viable axons and deposition of the degraded myelin basic
      protein. The data suggest that LIF signals survival in oligodendrocytes after
      SCI, prevents the secondary wave of demyelination, and thereby reduces inhibitory
      myelin deposits.

PMID- 16957589
TI  - Electroencephalographic responses to intraoperative subthalamic stimulation.
AB  - This study reports the effects of intraoperative stimulation of the subthalamic
      nucleus on brain electrical activity in advanced Parkinson's patients. To our
      knowledge, this is the first study about electroencephalographic responses in the
      very early phase of deep brain stimulation, during the implantation of the
      electrodes. We found an increase of gamma band bilaterally over the sensorimotor
      cortex in the range 45-55 Hz, which was associated with clinical improvement as
      assessed by means of muscle rigidity decrease. These results indicate that the
      electroencephalographic gamma responses to deep brain stimulation are present at
      the very beginning of the treatment process, and may help better understand the
      short and long-tem effects of deep brain stimulation.

PMID- 16957590
TI  - A suprachiasmatic nucleus projecting retinal ganglion cell exhibits an unusually
      large dendritic field in the hamster.
AB  - The majority of retinal ganglion cells innervating the suprachiasmatic nucleus
      are intrinsically light sensitive, while the rest are conventional ganglion cells
      that collect inputs through conventional photoreceptors. Here we report a rarely
      encountered ganglion cell that had a dendritic field covering approximately 14.4%
      of retinal surface and its processes ramified in both the inner and the outer
      plexiform layers. This cell could have a potential role in detecting luminance
      changes over a large area of retinal surface.

PMID- 16957591
TI  - Nitric oxide in cerebrospinal fluid and local inducible nitric oxide synthase
      after cauda equina compression in rats.
AB  - We investigated the time course of changes in nitric oxide metabolite (NO2- plus
      NO3-: NOx) levels in the cerebrospinal fluid and the expression of local
      inducible nitric oxide synthase following cauda equina compression in rats.
      Cerebrospinal fluid NOx levels were significantly increased from 12 h to 3 days
      after compression, and decreased thereafter. Histologically, inducible nitric
      oxide synthase immunoreactivity was observed in macrophages that infiltrated the
      dura mater on days 1 and 3 after compression, but not in foamy macrophages in the
      parenchyma of the cauda equina observed afterwards. The pattern of NOx levels
      coincided with the appearance of inducible nitric oxide synthase labeled
      macrophages, indicating a critical role of these cells as the main synthesizers
      of NOx in the acute stage of cauda equina compression.

PMID- 16957592
TI  - Decreased activation of anterior cingulate cortex in the working memory of the
      elderly.
AB  - We examined aging effects on activation in the anterior cingulate cortex during a
      verbal working memory using functional magnetic resonance imaging. Ten young
      (mean age 25 years) and 10 elderly (mean age 69 years) healthy adults performed
      the reading span test in which performance reflects individual differences in
      verbal working memory. We found an age-related difference in executive function
      in the prefrontal cortex; younger participants showed significant anterior
      cingulate cortex activation whereas the elderly did not. We found that the
      anterior cingulate cortex plays a critical role in executive function related to
      working memory. We found that behavioral deficits in verbal working memory
      because of aging result from the deterioration of cognitive control owing to
      decreased activation of the anterior cingulate cortex.

PMID- 16957593
TI  - Brain responses of explicit and implicit memory: An event-related potential
      study.
AB  - Implicit memory is acquired by an unintentional or unconscious learning.
      Recognition memory involves either automatic knowing or consciously controlled
      remembering. We provided an event-related potential paradigm capable of
      differentiating memory for the explicitly learned, implicitly learned and
      unstudied materials. In the explicit memory, we obtained both frontal (controlled
      retrieval) and parietal (recollection) old/new effects. In the implicit memory,
      we found persistent occipitotemporal activation (visual priming) and late
      attenuation in the temporoparietooccipital (repetition suppression). Event
      related potential provides an insight into the dissociable mechanism of memory
      function that supports the dual process model with an enhanced temporal
      resolution on the dynamic process of both explicit perceptual learning and
      implicit perceptual priming.

PMID- 16957594
TI  - Scopolamine attenuates tinnitus-related plasticity in the auditory cortex.
AB  - High doses of salicylate induce a temporary hearing deficit and a temporary
      subjective tinnitus in humans and animals. In animals, salicylate suppresses
      activity in the ascending auditory system but generates activity and plasticity
      in the auditory cortex and central amygdala. In addition to changes in the
      auditory system evoked by hearing impairment, enhanced stress may be crucial for
      the salicylate-induced alterations in the auditory cortex. The central amygdala
      responds to stress, and may influence cortical excitability and plasticity
      through cholinergic mechanisms. We investigated whether salicylate-induced
      plasticity in the auditory cortex is prevented by blocking cortical cholinergic
      receptors with the muscarinic antagonist scopolamine. Scopolamine suppresses
      salicylate-induced plasticity in the auditory cortex and, therefore, may be
      effective in suppressing the tinnitus sensation.

PMID- 16957595
TI  - Reduction of inhibition in the inferior colliculus after inner hair cell loss.
AB  - Effects of carboplatin-induced partial loss of inner hair cells on rate-level
      functions of neurons in the central nucleus of the inferior colliculus of the
      same chinchillas before and 1-3 months after carboplatin treatment were examined.
      Partial inner hair cell loss caused only a small elevation of response thresholds
      but induced a significant increase in the proportion of monotonic and a
      significant decrease in the proportion of non-monotonic rate-level functions at
      the characteristic frequency of 210 multiunits. This indicates that inhibition in
      the inferior colliculus is reduced after sensory deafferentation. We conclude
      that some of the functional changes reported in the auditory cortex after
      peripheral deafferentation are already realized at the level of the inferior
      colliculus.

PMID- 16957596
TI  - Odour encoding in olfactory neuronal networks beyond synchronization.
AB  - It has been suggested that odour encoding in olfactory systems occurs by
      synchronized firing in neuronal populations. Neurons correlated in terms of the
      Lempel-Ziv distance of spike trains and the sequential superparamagnetic
      clustering algorithm belong to the same cluster if they show similar, but not
      necessarily synchronous, firing patterns. Using multielectrode array recordings
      from the rat olfactory bulb, we have determined cluster incidence and stability
      in the neuronal network using both the Lempel-Ziv distance and a measure of
      synchronization. In the Lempel-Ziv paradigm, we found pronounced stabilization
      and destabilization effects in the neuronal network in response to odour
      presentation when compared with the synchronization paradigm. This suggests that
      synchronization alone may be insufficient for understanding olfactory coding.

PMID- 16957597
TI  - Self-initiated gait increases susceptibility to the moving platform after-effect.
AB  - Walking onto a stationary platform previously experienced as moving results in a
      large forward sway, despite awareness of the changing context. This after-effect
      demonstrates aberrant motor prediction. Here, we compared after-effect magnitude
      when gait initiation was either externally triggered or self-initiated. Both
      participant groups adapted their walking speed similarly when walking onto the
      moving platform. When it was kept stationary however, after-effect magnitude was
      more than doubled in the self-initiated group. We attribute this to a stronger
      association made between the action (gait initiation) and its consequence
      (platform movement) when the action is initiated by oneself. This increased sense
      of agency reduces the ability to switch off the acquired motor response when it
      is no longer appropriate.

PMID- 16957598
TI  - ATP potentiates neurotransmission in the rat trigeminal subnucleus caudalis.
AB  - Ionotropic purine receptors (P2X) have been implicated in nociceptive
      neurotransmission. In this study, we examine the actions of the P2X receptor
      agonist alpha,beta methylene adenosine 5'-triphosphate on excitatory
      neurotransmission in neurons in the deep and superficial laminae of the
      trigeminal spinal subnucleus caudalis (Vc), which receives nociceptive inputs
      from the craniofacial region. Alpha, beta methylene adenosine 5'-triphosphate
      caused an increase in spontaneous excitatory neurotransmission (miniature
      excitatory postsynaptic currents) in neurons in deep but not superficial laminae
      of Vc; this effect could be inhibited by the P2X receptor antagonist 2,3-O-2,4,6
      trinitrophenyl-ATP. Conversely, the TRPV1 agonist capsaicin caused an increase in
      miniature excitatory postsynaptic currents in neurons in the superficial but not
      deep laminae. These data suggest that alpha,beta methylene adenosine 5'
      triphosphate acts on presynaptic terminals to increase glutamatergic
      neurotransmission in deep Vc neurons.

PMID- 16957599
TI  - Lexical-semantic processes in children with specific language impairment.
AB  - The current study used event-related brain potentials to investigate lexical
      semantic processing of words in sentences spoken by children with specific
      language impairment and children with normal language development. Children heard
      correct sentences and sentences with a violation of the selectional restriction
      of the verb. Control children showed an N400 effect followed by a late positivity
      for the incorrect sentences. In contrast, children with specific language
      impairment showed no N400 effect but did show a late, broadly distributed
      positivity. This absence of the N400 effect is due to a relatively large
      negativity for correct sentences, suggesting weaker lexical-semantic
      representations of the verbs and their selectional restrictions in children with
      specific language impairment.

PMID- 16957600
TI  - Prenatal stress suppresses cell proliferation in the early developing brain.
AB  - Although prenatal stress has been repeatedly shown to inhibit adult neurogenesis
      in the dentate gyrus of offspring, its effects on embryonic and early postnatal
      brain development are not well described. Here, using the cell proliferation
      marker 5-bromo-2'-deoxyuridine, we examine for the first time the effect of
      prenatal stress at the embryonic stage on cell proliferation in the hippocampus,
      nucleus accumbens and amygdala. We show that prenatal stress induces a
      significant decrease in density of 5-bromo-2'-deoxyuridine-positive cells in the
      nucleus accumbens (40%) and hippocampus (60%), and a nonsignificant decrease in
      the amygdala (30%). Taken together, these results demonstrate the adverse effects
      of prenatal maternal stress on early development in limbic brain regions and the
      potential mechanisms are discussed.

PMID- 16957601
TI  - Astrocytogenesis of embryonic stem-cell-derived neural stem cells: Default
      differentiation.
AB  - Neural stem cells differentiate from embryonic stem cells via formation of neural
      stem spheres under free-floating conditions in astrocyte-conditioned medium.
      Subsequent culture of neural stem spheres on an adhesive substrate with
      fibroblast growth factor-2 promotes the migration of neural stem cells onto the
      substrate, resulting in an increase in the number of cells. These embryonic stem
      cell-derived neural stem cells can be differentiated almost exclusively into
      astrocytes by withdrawing fibroblast growth factor-2 from the medium without any
      additional instructions.

PMID- 16957602
TI  - Xylazine promotes axonal regeneration in the crushed optic nerve of adult rats.
AB  - Xylazine, an alpha-2 adrenergic agonist, activates the endogenous trophic factors
      and neuronal survival signaling. Here, we tested the regenerative effect of
      xylazine on damaged optic nerve axons in adult rats. After optic nerve crush,
      xylazine was intraperitoneally injected into three groups of rats: a single
      administration immediately after the crush, intermittent administration, and
      daily administration. On day 14, the regenerated axons were quantitatively
      evaluated by anterograde labeling. Everyday administration but neither single nor
      intermittent administration markedly increased the number of labeled axons beyond
      the crush site, with upregulation of growth-associated protein-43 in the ganglion
      cell layer and the regenerated axons. It was concluded that xylazine promotes
      axonal regeneration in damaged optic nerves of adult rats.

PMID- 16957603
TI  - The bed nucleus of the stria terminalis modulates baroreflex in rats.
AB  - In the present study, we report the effect of bed nucleus of stria terminalis
      (bed nucleus) ablation caused by bilateral microinjections of the nonselective
      synapse blocker CoCl2 on the baroreflex response in rats. Reversible ablation of
      the bed nucleus by bilateral microinjection of CoCl2 did not affect baseline
      blood pressure or heart rate, suggesting no tonic influence of bed nucleus on the
      cardiovascular system. Pretreatment with CoCl2 did not affect the tachycardic
      response to blood pressure decreases caused by intravenous infusion of sodium
      nitroprusside, but enhanced bradycardic responses evoked by blood pressure
      increases caused by intravenous infusion of phenylephrine. Present data suggest
      that synapses within the bed nucleus have a tonic inhibitory influence on the
      baroreflex parasympathetic component.

PMID- 16957604
TI  - Neurosteroids regulate mouse aggression induced by anabolic androgenic steroids.
AB  - Anabolic androgenic steroid abuse triggers impulsive aggression, anxiety, and
      depression, which suggests a dysfunction of GABAergic neurotransmission. Socially
      isolated female mice that have received testosterone propionate (1.45
      micromol/kg) treatment for 3 weeks during social isolation express aggression,
      neurosteroid downregulation, and changes in the cortical mRNA expression of
      several gamma-aminobutyric acid type A receptor subunits (alpha1, alpha2, gamma2
      are decreased by 30-40%, and alpha4 and alpha5 are increased by 50%).
      Administration of allopregnanolone or the potent selective brain steroidogenic
      stimulant S-norfluoxetine, in doses (1.8-3.6 micromol/kg) that fail to inhibit 5
      hydroxytryptamine reuptake, normalizes olfactory bulb neurosteroid level
      downregulation and abolishes aggression. This work underscores the role of
      neurosteroids in the regulation of aggression elicited by testosterone propionate
      in socially isolated female mice.

PMID- 16957605
TI  - A functional magnetic resonance imaging investigation of short-term source and
      item memory for negative pictures.
AB  - We investigated the hypothesis that arousal recruits attention to item
      information, thereby disrupting working memory processes that help bind items to
      context. Using functional magnetic resonance imaging, we compared brain activity
      when participants remembered negative or neutral picture-location conjunctions
      (source memory) versus pictures only. Behaviorally, negative trials showed
      disruption of short-term source, but not picture, memory; long-term picture
      recognition memory was better for negative than for neutral pictures. Activity in
      areas involved in working memory and feature integration (precentral gyrus and
      its intersect with superior temporal gyrus) was attenuated on negative compared
      with neutral source trials relative to picture-only trials. Visual processing
      areas (middle occipital and lingual gyri) showed greater activity for negative
      than for neutral trials, especially on picture-only trials.

PMID- 16957606
TI  - Quantification of distension in rat cerebral perforating arteries.
AB  - We developed a novel cerebral angiography procedure for rodents using
      monochromatic synchrotron radiation X-rays and obtained images of rat cerebral
      perforating arteries for the first time. In normotensive rat, hypercapnia rapidly
      distended the perforators between 3 and 15 min after induction and major trunk
      vessels distended more rapidly in 3-6 min. Systemic hypotension made by stepwise
      hemorrhage distended the perforators up to 158% of control values but constricted
      most of the large cerebral trunk vessels. In spontaneous hypertensive rats,
      systemic hypotension-induced distension disappeared in perforators, indicating
      that perforators with chronic hypertension lose their autoregulatory
      distensibility.

PMID- 16957607
TI  - Differential influences of negative emotion on spatial and verbal working memory:
      Evidence from event-related potential and source current density analysis.
AB  - We used the event-related potential technique to assess the influences of
      negative emotion on spatial and verbal working memory with a modified n-back
      task. In both spatial and verbal tasks, the anterior late positive component and
      the posterior P300 were affected by negative emotion. These effects were,
      however, greater in spatial tasks than in verbal ones. Especially, the parietal
      P300 was reduced by negative emotion in spatial tasks, but not in verbal tasks.
      Current density analysis revealed high current density in the frontal-parietal
      cortex, but only in the spatial tasks. The results suggest differential effects
      of negative emotion on spatial and verbal working memory and that the frontal
      parietal cortex may be the area where negative emotion and spatial working memory
      interact.

PMID- 16957608
TI  - Memory-based detection of rare sound feature combinations in anesthetized rats.
AB  - It is unclear whether the ability of the brain to discriminate rare from
      frequently repeated combinations of sound features is limited to the normal
      sleep/wake cycle. We recorded epidural auditory event-related potentials in
      urethane-anesthetized rats presented with rare tones ('deviants') interspersed
      with frequently repeated ones ('standards'). Deviants differed from standards
      either in frequency alone or in frequency combined with intensity. In both cases,
      deviants elicited event-related potentials exceeding in amplitude event-related
      potentials to standards between 76 and 108 ms from the stimulus onset, suggesting
      the independence of the underlying integrative and memory-based change detection
      mechanisms of the brain from the normal sleep/wake cycle. The relations of these
      event-related potentials to mismatch negativity and N1 in humans are addressed.

PMID- 16957610
TI  - Solving the problem pelvic ultrasound with magnetic resonance imaging.
AB  - Ultrasound is the screening method of choice for evaluation of pelvic anatomy and
      abnormalities of the female pelvis. It allows for detailed assessment of the
      uterus, endometrium, and ovaries. However, there are times when the sonographic
      diagnosis is nonspecific. This review article details the use of magnetic
      resonance imaging for assessment of uterine duplication anomalies, adnexal and
      uterine masses, and for aiding in the assessment of pregnant patients with
      nonspecific sonographic findings in the pelvis.

PMID- 16957611
TI  - Controversies in transrectal ultrasonography and prostate biopsy.
AB  - Transrectal ultrasound-guided biopsy of the prostate is the gold standard for the
      detection of prostate cancer. In its current form, transrectal gray-scale
      ultrasound is unable to differentiate malignant prostate tissue from benign
      tissue. The general indications for performing a sonographic guided biopsy of the
      prostate are an abnormal digital rectal examination or an abnormal prostate
      specific antigen (PSA). Several controversial areas remain: the ideal number of
      biopsy cores, the use of PSA velocity, free PSA, PSA density, age- and race
      adjusted PSA, the use of local anesthetics, and the overall best patient
      preparation methods, including such topics as routine antibiotic prophylaxis or
      bowel enemas, remain unsettled. There are also unanswered questions regarding
      repeat biopsy and protocols for managing patients with a diagnosis of high-grade
      intraepithelial neoplasia. This article will explore some of the current
      controversies and review the pertinent literature.

PMID- 16957612
TI  - A practical approach to fetal chest masses.

PMID- 16957613
TI  - Focal tumor ablation: a new era in cancer therapy.
AB  - This article describes an approach to image-guided tumor ablation, a major tool
      for cancer treatment in interventional oncology. An overview of the discipline of
      tumor ablation is followed by a review of the diseases affecting the liver; then,
      more in-depth discussion of percutaneous ethanol injection, radiofrequency
      ablation, cryoablation, and microwave ablation is offered. Inasmuch as ultrasound
      is usually the best imaging modality for applicator placement in the liver and
      kidney, particular attention will be given to the merits and techniques of this
      guidance method.

PMID- 16957635
TI  - Influence of neurally adjusted ventilatory assist and positive end-expiratory
      pressure on breathing pattern in rabbits with acute lung injury.
AB  - OBJECTIVE: To evaluate the influence of neurally adjusted ventilatory assist
      (NAVA) and positive end-expiratory pressure (PEEP) on the control of breathing in
      rabbits with acute lung injury. DESIGN: Prospective animal study. SETTING:
      Experimental laboratory in a university hospital. SUBJECTS: Male White New
      Zealand rabbits (n = 18). INTERVENTION: Spontaneously breathing rabbits with
      hydrochloric acid-induced lung injury were ventilated with NAVA and underwent
      changes in NAVA gain and PEEP (six nonvagotomized and five vagotomized). Seven
      other nonvagotomized rabbits underwent 4 hrs of ventilation with hourly titration
      of PEEP, Fio2, and NAVA gain. MEASUREMENTS AND MAIN RESULTS: We studied diaphragm
      electrical activity, respiratory pressures, and breathing pattern. After lung
      injury, 0 cm H2O of PEEP resulted in high tonic and no discernible phasic
      diaphragm electrical activity in the nonvagotomized rabbits; stepwise increases
      in PEEP (up to 11.7 +/- 2.6 cm H2O) reduced tonic but increased phasic diaphragm
      electrical activity. Increasing the NAVA gain reduced phasic diaphragm electrical
      activity to almost half and abolished esophageal pressure swings. Tidal volume
      remained at 4-5 mL/kg, and respiratory rate did not change. In the vagotomized
      group, lung injury did not induce tonic activity, and phasic activity and tidal
      volume were several times higher than in the nonvagotomized rabbits. Four hours
      of breathing with NAVA restored breathing pattern and neural and mechanical
      breathing efforts to pre-lung injury levels. CONCLUSIONS: Acute lung injury can
      cause a vagally mediated atypical diaphragm activation pattern in spontaneously
      breathing rabbits. Modulation of PEEP facilitates development of phasic diaphragm
      electrical activity, whereupon implementation of NAVA can efficiently maintain
      unloading of the respiratory muscles without delivering excessive tidal volume in
      rabbits with intact vagal function.

PMID- 16957636
TI  - When is critical care medicine cost-effective? A systematic review of the cost
      effectiveness literature.
AB  - BACKGROUND: Receiving care in an intensive care unit can greatly influence
      patients' survival and quality of life. Such treatments can, however, be
      extremely resource intensive. Therefore, it is increasingly important to
      understand the costs and consequences associated with interventions aimed at
      reducing mortality and morbidity of critically ill patients. Cost-effectiveness
      analyses (CEAs) have become increasingly common to aid decisions about the
      allocation of scarce healthcare resources. OBJECTIVES: To identify published
      original CEAs presenting cost/quality-adjusted life year or cost/life-year ratios
      for treatments used in intensive care units, to summarize the results in an
      accessible format, and to identify areas in critical care medicine that merit
      further economic evaluation. METHODS: We conducted a systematic search of the
      English-language literature for original CEAs of critical care interventions
      published from 1993 through 2003. We collected data on the target population,
      therapy or program, study results, analytic methods employed, and the cost
      effectiveness ratios presented. RESULTS: We identified 19 CEAs published through
      2003 with 48 cost-effectiveness ratios pertaining to treatment of severe sepsis,
      acute respiratory failure, and general critical care interventions. These ratios
      ranged from cost saving to 958,423 US dollars/quality-adjusted life year and from
      1,150 to 575,054 US dollars/life year gained. Many studies reported favorable
      cost-effectiveness profiles (i.e., below 50,000 US dollars/life year or quality
      adjusted life year). CONCLUSIONS: Specific interventions such as activated
      protein C for patients with severe sepsis have been shown to provide good value
      for money. However, overall there is a paucity of CEA literature on the
      management of the critically ill, and further high-quality CEA is needed. In
      particular, research should focus on costly interventions such as 24-hr
      intensivist availability, early goal-directed therapy, and renal replacement
      therapy. Recent guidelines for the conduct of CEAs in critical care may increase
      the number and improve the quality of future CEAs.

PMID- 16957637
TI  - Methylene blue added to a hypertonic-hyperoncotic solution increases short-term
      survival in experimental cardiac arrest.
AB  - OBJECTIVE: Methylene blue (MB), a free-radical scavenger inhibiting the
      production and actions of nitric oxide, may counteract excessive vasodilatation
      induced by nitric oxide during cardiac arrest. Effects of MB in cardiac arrest
      and cardiopulmonary resuscitation were investigated. DESIGN: Randomized,
      prospective, laboratory animal study. SETTING: University animal research
      laboratory. SUBJECTS: A total of 63 piglets of both sexes. INTERVENTIONS: A pig
      model of extended cardiac arrest (12 mins of untreated cardiac arrest and 8 mins
      of cardiopulmonary resuscitation) was employed to assess the addition or no
      addition of MB to a hypertonic saline-dextran solution. These two groups (MB and
      hypertonic saline-dextran group [MB group] and hypertonic saline-dextran-only
      group) of 21 animals were each compared with a group receiving isotonic saline (n
      = 21). MEASUREMENTS AND MAIN RESULTS: Although the groups were similar in
      baseline values, 4-hr survival in the MB group was increased (p = .02) in
      comparison with the isotonic saline group. Hemodynamic variables were somewhat
      improved at 15 mins after restoration of spontaneous circulation in the MB group
      compared with the other two groups. The jugular bulb levels of 8-isoprostane
      prostaglandin F2alpha and 15-keto-dihydro-prostaglandin F2alpha (indicators of
      peroxidation and inflammation) were significantly decreased in the MB group
      compared with the isotonic saline group. Significant differences were recorded
      between the three groups in levels of protein S-100beta (indicator of neurologic
      injury), with lower levels in the MB group compared with the isotonic saline and
      hypertonic saline-dextran-only groups. Troponin I and myocardial muscle creatine
      kinase isoenzyme arterial concentrations (indicators of myocardial damage) were
      also significantly lower in the MB group. CONCLUSIONS: MB co-administered with a
      hypertonic-hyperoncotic solution increased 4-hr survival vs. saline in an
      experimental porcine model of cardiac arrest and reduced oxidative, inflammatory,
      myocardial, and neurologic injury.

PMID- 16957638
TI  - Pulsed steroid therapy is an effective treatment for intractable hyperemesis
      gravidarum.
AB  - OBJECTIVE: Intractable hyperemesis gravidarum remains a serious cause of
      morbidity among pregnant women. If not controlled, hyperemesis gravidarum can
      lead to severe disability, electrolyte and acid base imbalance, and even various
      organ system dysfunctions. From the successful use of steroids for chemotherapy
      induced emesis, corticosteroids might prove useful in hyperemesis gravidarum. The
      purpose of this study was to compare the efficacy of pulsed hydrocortisone
      therapy with that of metoclopramide for the management of intractable hyperemesis
      gravidarum. DESIGN: Prospective, double-blind study. SETTING: Intensive care unit
      of Ain Shams University Maternity Hospital. PATIENTS: Forty patients aged 19-34
      yrs having a normal appearing intrauterine pregnancy, of < or =16 wks gestation,
      admitted to the intensive care unit with intractable hyperemesis meeting the
      study criteria. INTERVENTIONS: Patients were randomly assigned to receive either
      intravenous hydrocortisone 300 mg as a daily dose or intravenous metoclopramide
      10 mg 3 times daily. After 3 days the hydrocortisone was tapered completely
      during the course of 1 wk, whereas the metoclopramide was continued without
      change for 1 wk. Patients were followed up daily during the therapy course and
      for 2 wks following intensive care unit discharge. MEASUREMENTS AND MAIN RESULTS:
      There was a significant reduction in vomiting episodes in the hydrocortisone
      group compared with the metoclopramide group (p < .0001). Within-patient analyses
      showed a significant reduction in mean vomiting episodes in the hydrocortisone
      group within the first 3 days (p < .0001). No patients from the hydrocortisone
      group but six of the patients receiving metoclopramide were readmitted for
      intractable vomiting within 1 wk from discharge. Five of them showed improvement
      on intravenous hydrocortisone therapy. CONCLUSIONS: A short course of
      hydrocortisone is an effective treatment for intractable hyperemesis gravidarum.

PMID- 16957639
TI  - Reduced burden of bacterial airway colonization with a novel silver-coated
      endotracheal tube in a randomized multiple-center feasibility study.
AB  - OBJECTIVE: To assess the feasibility and safety of the respiratory infection
      control (RIC) device, a silver-coated endotracheal tube, and its effect on
      bacterial burden in the airways. DESIGN: Prospective, randomized, single-blind,
      multiple-center study. SETTING: Three hospitals in Spain and one in the United
      States. PATIENTS: Patients were eligible adults who required mechanical
      ventilation for > or =24 hrs and did not have respiratory infections. One hundred
      forty-nine patients were intubated and analyzed for safety; 121 were intubated >
      or =24 hrs and analyzed for tube colonization; 67 had negative baseline
      quantitative endotracheal aspirates and were analyzed for quantitative
      endotracheal aspirates colonization. INTERVENTIONS: Intubation with the RIC
      device or a control endotracheal tube. MEASUREMENTS AND MAIN RESULTS: The RIC
      device was associated with delayed colonization on the tube compared with the
      control device at the threshold of ++, +++, or > or =10(4) colony-forming
      units/mL (p = .02, log-rank test; p = .10, Wilcoxon's test) and in quantitative
      endotracheal aspirates at > or =10(6) colony-forming units/mL (p = .08, log-rank
      test; p = .05, Wilcoxon's test). The RIC device was associated with reduced
      colonization rate by days on the tube (p = .04, Wilcoxon's test) and in
      quantitative endotracheal aspirates (p = .05, Wilcoxon's test) at the same
      thresholds. The RIC device was associated with lower maximal bacterial burden in
      tracheal aspirates for 7 days (mean log-transformed burden, 4.2 +/- 2.3 vs. 5.5
      +/- 1.7 log colony-forming units/mL; p = .02, Wilcoxon's test). Other between
      group differences favored the RIC device but were not significant. Five adverse
      events were considered device related, including three events in the RIC group
      and two events in the control group. CONCLUSIONS: In this prospectively planned,
      preliminary analysis, the RIC device was feasible and well tolerated. Larger
      studies are needed to determine whether delayed colonization, reduced
      colonization rate, and decreased bacterial burden will decrease the incidence of
      ventilator-associated pneumonia.

PMID- 16957640
TI  - Rapid recovery protocols and minimally invasive surgery help achieve high knee
      flexion.
AB  - Although the primary goal of total knee arthroplasty is to relieve pain, the
      attainment of high flexion has emerged as an important secondary goal. Clinical
      pathways are evolving and focus on rapid recovery. The entire perioperative
      process for the patient and family, including office and hospital procedures, has
      been streamlined and patients are advised from the initial evaluation they will
      be able to quickly return to activities of daily living. Currently, patients are
      out of bed within hours of surgery, engaging in activities that require a
      substantial range of motion in the treated knee. They are frequently discharged
      directly to home within 24 to 48 hours. We retrospectively reviewed two groups of
      patients undergoing primary total knee arthroplasty whose perioperative
      management differed only by surgical approach, namely, standard versus less
      invasive. Refined perioperative protocols in combination with a less invasive,
      mini-arthrotomy approach using special instrumentation resulted in earlier
      discharge to home, higher range of motion and improved clinical and pain scores.

PMID- 16957641
TI  - Computer-assisted navigation in TKA: where we are and where we are going.
AB  - When compared to standard intramedullary and extramedullary referencing systems,
      computer-assisted navigation systems have been shown in multiple randomized
      studies to increase the accuracy of bone resections in total knee arthroplasty.
      Accuracy to within 1 degrees in the coronal plane resections can routinely be
      obtained. Recent modifications of the software programs address the problem of
      proper soft tissue balance. Newer techniques of bone morphing have obviated the
      use of preoperative imaging in most cases. Despite these advances, the systems
      remain somewhat cumbersome to use and costly to acquire. As these limitations are
      addressed, computer-assisted navigation may become a valuable part of the knee
      surgeon's armamentarium, especially for the patient with a deformed femur or
      tibia in whom conventional navigation instruments are difficult to use
      accurately.

PMID- 16957642
TI  - The benefit of aspirin chemoprophylaxis for thromboembolism after total knee
      arthroplasty.
AB  - The threat of thromboembolic events after total knee arthroplasty has been
      substantially reduced during the past decade. Currently, the risk of fatal
      pulmonary embolism is approximately 0.1%. This is due to a confluence of changes
      in our medical practices, including early mobilization, less traumatic surgery,
      increased use of regional anesthesia, pneumatic compression devices, and
      chemoprophylactic agents. Because many chemoprophylactic agents are associated
      with an increased risk of bleeding, we have chosen aspirin as our preferred
      method of chemoprophylaxis. This study seeks to determine if aspirin is as
      effective as newer chemoprophylactic agents as judged by the prevalence of fatal
      or nonfatal pulmonary embolus, readmission for deep venous thrombosis, and risk
      of bleeding. Aspirin was the principle chemoprophylactic agent for 3473
      consecutive patients having total knee arthroplasty. All patients were followed
      for a minimum of 6 weeks. There were nine deaths: two from pulmonary embolism,
      five cardiac events, one stroke, and one fat embolism. Three cardiac-related
      deaths occurred in patients for whom pulmonary embolism could not definitively be
      ruled out. Therefore, the best case and worst case scenarios for fatal pulmonary
      embolism were 0.06% and 0.14%, respectively. Thirteen patients underwent
      reoperation for hematoma (0.4%). Therefore, we have demonstrated aspirin combined
      with early mobilization, regional anesthesia, foot pumps, and improved surgical
      techniques is safer than and equally efficacious as other chemoprophylaxis
      agents.

PMID- 16957643
TI  - Nonspecific lower-back pain: surgical versus nonsurgical treatment.

PMID- 16957645
TI  - Safety of computer-assisted surgery for cannulated hip screws.
AB  - Computer-assisted orthopaedic surgery has developed considerably during the past
      few years. Several manufacturers produce hardware and software for use in trauma
      surgery. Validation of these systems before clinical application is mandatory to
      be sure they work accurately and safely. The accuracy of surgical performance is
      highly correlated with the cut-out percentages of hip screws. In a standardized
      operative setting, three cannulated hip screws were inserted in each of 20
      sawbones. The screws were positioned either by fluoroscopic navigation technique
      or by conventional operative technique depending on randomization. Our primary
      aim was to assess whether computer-navigated screw fixation is equally safe
      compared with conventional screw fixation using fluoroscopy. To determine safety,
      we investigated number of drilling attempts, screw position, and radiation time.
      Secondary to these safety parameters, we also compared the operating time between
      the two procedures to assess the efficiency of computer navigation. Statistical
      analysis showed no differences regarding accuracy of screw position. Computer
      assisted surgery resulted in fewer drilling attempts and less radiation time,
      with a similar operation time. We believe the currently used navigation system is
      safe and accurate.

PMID- 16957646
TI  - Deformity correction with external fixator in pseudoachondroplasia.
AB  - Patients with pseudoachondroplasia have complex, difficult to correct deformities
      including angular deformity, rotational deformity, and ligament laxity. We
      retrospectively reviewed seven patients (two children, five adults) with 26
      segmental deformities (12 femora, 14 tibiae). We performed bilateral femoral and
      tibial osteotomies in six patients and bilateral tibial osteotomies in one
      patient. Distraction osteogenesis was used in 20 segments and acute deformity
      correction was done in six segments. External fixation was applied to all
      segments. Of 26 segments, there were five good, 12 fair, and nine poor
      radiographic results with nine major and 12 minor complications. Recurrent
      deformity in children and refracture in adults were related to poor results. Of
      14 limbs, there were four good, five fair, and five poor clinical results with
      five major and 14 minor complications. Knee stiffness was the most common
      complication related to poor results in our series, and occurred particularly in
      patients with simultaneous correction of the ipsilateral tibial and femoral
      deformities. Therefore, two-stage surgery including bilateral tibial osteotomies
      first and then bilateral femoral osteotomies is recommended instead of
      simultaneous correction of the ipsilateral tibial and femoral deformities to
      avoid knee stiffness.

PMID- 16957647
TI  - Popliteal sarcomas: presentation, prognosis, and limb salvage.
AB  - Soft tissue sarcomas of the popliteal fossa are rare diseases. Resection is
      challenging because of their extracompartmental location and proximity to
      neurovascular structures. Their prognosis is inferior to intracompartmental
      extremity soft tissue sarcomas. We ascertained the mode of initial presentation,
      the rates of local recurrence and distant metastasis, and the morbidity and
      complications of limb salvage procedures. We retrospectively analyzed the data of
      29 consecutive patients operated on between 1989 and 2003. The median followup
      was 79 months. Sixteen, five, and eight patients were diagnosed with high-,
      intermediate-, and low-grade tumors, respectively. High-grade tumors were smaller
      than low- and intermediate-grade tumors. Thirty-one percent of patients presented
      with localized pain. Of the 26 patients who had primary limb salvage resections,
      14 had negative surgical margins, six had close margins, and six had positive
      margins. Seventeen patients were treated with radiotherapy and 10 patients
      received chemotherapy. The local recurrence rate was 10.3%, four patients with
      high-grade tumors had distant metastasis, and the limb-salvage rate was 86.2%.
      Postoperatively, six patients experienced wound dehiscence and four had mild
      flexion contractures. Soft tissue sarcomas of the popliteal fossa have an
      atypical presentation. Limb salvage can be accomplished in most patients with low
      morbidity and good systemic and local control.

PMID- 16957648
TI  - Case report: a thigh mass resulting from polyethylene wear of a revision total
      hip arthroplasty.
AB  - The case of a 60-year-old man who had an enlarging thigh mass seen during a
      routine 12-year examination of a cementless revision total hip arthroplasty is
      presented. Aspiration of the mass yielded more than 200 cc of thick yellow fluid.
      Cytopathologic examination disclosed material consistent with polyethylene wear
      debris. The porous titanium acetabular and femoral components were not loose.
      Reoperation was recommended despite minimal symptoms, because the fluid-filled
      mass recurred after aspiration. At the time of reoperation, the components
      appeared well fixed and a linerhead exchange was performed. One year after
      surgery, the mass had not recurred and the patient had minimal symptoms.

PMID- 16957649
TI  - Thoracic and lumbar pedicle morphometry in achondroplasia.
AB  - For safe pedicle screw insertion, knowing pedicle anatomy is essential. Pedicle
      morphometry in achondroplasia has not been quantitatively described. Therefore,
      we analyzed 302 thoracic and lumbar pedicles in 11 patients using computed
      tomography. Transverse endosteal diameter, screw path length, transverse angle,
      sagittal diameter, and sagittal angle were calculated. We analyzed for safe screw
      length, size, and trajectory. The data were compared with that on healthy people
      of different races. In patients with achondroplasia, the maximum endosteal
      diameter was at L5 and the minimum was at T5. Screw path length was longest at L2
      and shortest at T2. Most dimensions were smaller compared with those of healthy
      people. Abnormal anteromedial transverse angulations were observed between T11 to
      L2. The maximum transverse angulations were at T2. Sagittal diameter was largest
      at T12 and smallest at T5. The maximum sagittal angle was seen at T2, and at L5
      it was caudal. At all levels except L5, the transverse diameter is the limiting
      factor for screw size. Six-millimeter screws can be used at L5. Screws that are
      35 mm or less are safe to use between T7 to L5. There are surgically important
      differences in the different angles and diameters of thoracic and lumbar pedicles
      of patients with achondroplasia and those of healthy people.

PMID- 16957650
TI  - Total knee arthroplasty in patients with greater than 20 degrees flexion
      contracture.
AB  - Fixed flexion contracture can present a technical challenge in total knee
      arthroplasty. Various techniques of addressing these deformities have been
      described including additional bony resection, ligamentous releases, and the use
      of increasing constraint. We retrospectively reviewed the clinical outcomes of 40
      patients (52 knees) with fixed flexion contracture greater than or equal to 20
      degrees treated with revision TKA and a stepwise algorithmic approach to treating
      the contracture. A cruciate-retaining device was used in 31 knees, a posterior
      stabilized design was used in 14, a posterior stabilized constrained device was
      used in five knees, and a rotating hinged design in was used in two knees. Full
      correction was achieved intraoperatively. Ninety-four percent of knees had less
      than 10 degrees residual contracture at an average followup of 37 months. We
      revised one case of postoperative instability in the posterior stabilized group
      and we had one infection in the cruciate-retaining group. No other revisions were
      performed. The stepwise algorithmic approach to treating fixed flexion deformity
      presented in this study in primary total knee arthroplasty is safe and effective.

PMID- 16957651
TI  - Quadriceps-sparing versus mini-subvastus approach in total knee arthroplasty.
AB  - In a prospective randomized double-blind study we compared the postoperative
      recovery and early results of two groups of 30 patients having total knee
      arthroplasty with minimally invasive techniques using either a mini-subvastus or
      a modified "quadriceps-sparing" approach. All knees were implanted with the same
      posterior-stabilized prosthesis (LPS-Flex, Zimmer, Warsaw, IN) by the same
      surgeon with the same dedicated set of downsized instruments. Epidural anesthesia
      with the same postoperative analgesia and rehabilitation protocol was used in all
      patients. Evaluation was performed preoperatively, postoperatively in the first
      week, and at 1 and 3 months. In five cases in the "quadriceps- sparing" group,
      the incision was extended a few cm to facilitate exposure. Tourniquet time,
      estimated blood loss, and postoperative pain were similar in the two groups.
      Active straight leg raising was achieved half a day earlier, on average, in the
      mini-subvastus group (1.9 vs 1.4 days). Average maximum active flexion was
      similar in the two groups at each interval, and reached 117 degrees and 119
      degrees at 3 months for the mini-subvastus and "quadriceps-sparing" group,
      respectively. We believe there was no difference between the mini-subvastus and
      "quadriceps-sparing" approach in relation to short term recovery or early
      results.

PMID- 16957652
TI  - Argon beam coagulation as an adjuvant for local control of giant cell tumor.
AB  - The argon beam coagulator is gaining popularity as an adjuvant therapy for
      treatment of giant cell tumors of bone. However, the effectiveness and functional
      implications of this treatment have not been assessed. To determine whether the
      argon beam coagulator could be a viable adjuvant treatment option, we examined
      the recurrence rate and functional outcome of patients with giant cell tumors who
      were treated with the argon beam coagulator, as an adjuvant to curettage and
      cementation. Thirty-seven patients who received argon beam coagulation as an
      adjuvant treatment for giant cell tumors diagnosed between 1993 and 2000 were
      identified. The median age of the patients was 32 years (range, 16-64 years). The
      mean followup was 73.7 months (range, 0.5-108 months). Three patients had osseous
      recurrences (8.3%) and one had a soft tissue recurrence. The 5-year Kaplan-Meier
      disease-free survival estimate was 87.2% (95% confidence interval, range, 76.3
      99.8). No patient had radiographic evidence of arthritis. The average
      Musculoskeletal Tumor Society score was 28. Short form-36 evaluation showed no
      change in functional or mental perception in these patients compared with US
      norms. These data suggest argon beam coagulation as an adjuvant therapy is
      associated with in a low rate of local recurrence and is a reasonable adjuvant
      treatment option.

PMID- 16957653
TI  - Endoscopic approach to acute pancreatitis.
AB  - This review focuses on the use of endoscopic techniques in the diagnosis and
      management of pancreatic disorders. Endoscopic retrograde
      cholangiopancreatography (ERCP) has been used primarily to evaluate and treat
      disorders of the biliary tree. Recently, endoscopic techniques have been adapted
      for pancreatic sphincterotomy, stenting, stricture dilation, treatment of duct
      leaks, drainage of fluid collections, and stone extraction via the major and
      minor papillae. In patients with acute and recurrent pancreatitis, ERCP carries a
      higher than average risk of post-ERCP pancreatitis. This risk can be reduced with
      the placement of a prophylactic pancreatic stent. Magnetic resonance
      cholangiopancreatography (MRCP) can establish the anatomy of the biliary and
      pancreatic ducts, identify pancreas divisum or pancreatic ductal strictures,
      depict bile duct stones, and demonstrate pancreatic or biliary duct dilation.
      Endoscopic ultrasound (EUS) provides a safer, less invasive, and often more
      sensitive measure for evaluating the pancreas and biliary tree, and allows some
      options for therapy. In acute and recurrent pancreatitis, EUS and MRCP can be
      used to establish a diagnosis; ERCP can be reserved for therapy.

PMID- 16957654
TI  - Gastroesophageal reflux disease symptoms on antisecretory therapy: acid, non
      acid, or no GERD.
AB  - A clinically important subset of patients with erosive esophagitis will not
      attain adequate symptom relief and healing on once-a-day proton pump inhibitor
      therapy. This is especially true in patients with frequent and nocturnal
      heartburn and in those with Los Angeles Grades C and D erosive esophagitis. The
      approach to evaluation and management of cases of refractory or difficult
      gastroesophageal reflux disease is the subject of this state-of-the-art review.

PMID- 16957655
TI  - Rifaximin: a non-absorbable antibiotic for prevention of travelers' diarrhea.

PMID- 16957656
TI  - Overuse of postpolypectomy surveillance colonoscopy.

PMID- 16957657
TI  - MMX mesalamine.
AB  - Most current drug delivery systems in the treatment of ulcerative colitis and
      Crohn's disease release the active drug at the least effective location for
      treatment. The pharmaceutical industry has been developing different delivery
      systems for Multi-Matrix System (MMX) mesalamine for the treatment of Crohn's
      disease and ulcerative colitis. The new oral mesalamine formulation is a once
      daily MMX tablet that delivers the mesalamine to the colon, making it most useful
      in the treatment of ulcerative colitis. The MMX coating matrix and coating system
      begin dissolution in the final portion of the ileum. This type of oral
      formulation may make MMX a preferred agent over other oral mesalamine and
      mesalamine-prodrug formulations that release the drug proximally in the
      gastrointestinal tract. Unlike previous formulations, it can be administered once
      daily for the treatment of ulcerative colitis.

PMID- 16957658
TI  - Best of DDW 2006.
AB  - Highlights from the 2006 Digestive Disease Week May 20-25, 2006, Los Angeles, CA.
      In this meeting review, many of our editorial board members report on Digestive
      Disease Week 2006. They highlight the most noteworthy presentations in their
      respective areas of expertise, including the latest treatments, technologies, and
      diagnostic advances in ulcerative colitis, Crohn's disease, Helicobacter pylori
      infection, gastroesophageal reflux disease, irritable bowel syndrome, colorectal
      cancer, pancreatic and biliary disease, and liver disease.

PMID- 16957659
TI  - Endoscopic therapy for pancreas divisum.

PMID- 16957661
TI  - Sedationless upper endoscopy.
AB  - The use of sedation with peroral passage of conventionally sized endoscopes for
      upper endoscopy is the standard practice for most endoscopists in the United
      States. The administration of sedatives requires time-consuming and resource
      intensive patient monitoring, has substantial cost, and can produce side effects
      and rare complications. Ultra-thin videoendoscopes (outer diameter less than 6
      mm) have been developed, can easily be passed transorally or transnasally without
      sedation, and have been shown to be well tolerated and accurate. Unsedated upper
      endoscopy can provide an efficient, cost-effective alternative to standard
      endoscopy, should be useful for endoscopic screening, and can be offered as an
      option to conventional sedated examination.

PMID- 16957662
TI  - Advances in esophageal imaging: practical applications for clinicians.
AB  - In the 1960s, the revolution in the diagnosis and management of gastrointestinal
      diseases began with the introduction of the first flexible fiber endoscope. Since
      then, the technologies have evolved greatly. Particularly in recent years, much
      emphasis has been placed on developing new gastrointestinal endoscopy
      technologies or techniques in order to provide a precise and even a "real time"
      endoscopic diagnosis. Magnification and high-resolution endoscopy,
      chromoendoscopy, and narrow band imaging stand at the forefront of the novel
      endoscopic techniques for the diagnosis of conditions such as squamous cell
      carcinoma, Barrett's esophagus, and gastroesophageal reflux disease. This review
      summarizes the recent advances in esophageal imaging and its practical
      applications for clinicians.

PMID- 16957663
TI  - Recent advances in endoscopic capsule imaging: see what we have been missing.
AB  - Depiction of the small intestine has always been a challenge because of its
      length and tortuosity. The development of capsule endoscopy has been a
      significant advance that has allowed for more complete small intestine
      evaluations. The capsule is disposable, captures 2 images per second, and has a
      battery life of approximately 8 hours. Images are transmitted to a data recorder
      via digital radio frequency communication, and downloaded to the workstation
      computer, where it can be read by a gastroenterologist. One of the complications
      of use is capsule retention; however, a patency capsule has been developed that
      indicates whether obstruction is present before capsule endoscopy is performed.
      Capsule endoscopy has renewed interest in the diagnosis and evaluation of small
      intestinal diseases, been partly responsible for increased research in this area,
      and led to the development of newer radiologic and endoscopic techniques to
      evaluate the small intestine.

PMID- 16957664
TI  - Advances in colonoscopic imaging.
AB  - Recent studies have indicated that the levels of protection against colorectal
      cancer provided by colonoscopy and polypectomy may be considerably lower than
      what was once commonly believed. Improvements in colonoscopic detection of
      neoplasia could be enormously beneficial in reducing the incidence of colorectal
      cancer related to missed lesions. Factors that interfere with detection of
      neoplasia during colonoscopy, as well as technologic advances that can improve
      both neoplasia detection and real-time determination of polyp histology, are
      reviewed.

PMID- 16957665
TI  - [Measurement of radiation exposure to a PET institution driver from patients
      injected with FDG].
AB  - With the recent increase in FDG-PET examinations, concern has mounted regarding
      radiation exposure to hospital staff and the general public from patients
      injected with FDG. Because our PET institution is located 15 km from the hospital
      that provides these examinations, a driver has been designated to transport
      patients injected with FDG. This study was designed to measure the radiation dose
      to the driver from these patients (n=28) and to compare it with the estimated
      dose. A pocket dosimeter was used to measure radiation exposure to the driver.
      When the distances between the driver and patient were 1.1 m and 1.9 m, mean
      measured doses were 7.31 microSv and 2.26 microSv, respectively, while mean
      estimated doses were 8.61 microSv and 2.82 microSv, respectively, per trip. It
      was presumed that maximum radiation exposure per year was between 3.02 mSv (1.1
      m) and 0.92 mSv (1.9 m). According to our data, the measured dose was 20% lower
      than the estimated dose. This discrepancy may be due to the difference between
      the volume source (measured dose) and point source (estimated dose).

PMID- 16957666
TI  - [Comparison of noise equivalent count rate and image quality for two-dimensional
      and three-dimensional PET scans].
AB  - The aim of this study was to investigate the correlation between noise equivalent
      count (NEC) rates and the signal-to-noise ratio (S/N) in reconstructed images.
      The NEC rates were determined using uniform 20 cm and 70 cm tall, 20 cm diameter
      cylinders filled with 11C. The phantoms were scanned in both two-dimensional and
      three-dimensional modes. The reconstructed image noise was evaluated using FBP
      and OSEM algorithms (4 iterations and 8 subsets). The images were filtered to a
      final image resolution of 6.5 mm. From the reconstructed image sets, averages and
      standard deviations of images were generated, from which the average image S/N
      (=average/standard deviation) was calculated within an 18 cm central ROI. The S/N
      of a central slice and an end slice was compared with the NEC. The NEC was found
      to have a linear relationship to the image S/N of all slices, depending on
      differences in noise properties specific to the reconstruction algorithm. In two
      dimensional mode, although the image S/N of the central slice and the edge slice
      showed a linear relationship with the NEC, in three-dimensional mode, the S/N of
      the central slice did not show a relationship with the NEC. The linear
      relationship was also found in both two- and three-dimensional acquisition modes,
      as well as for the different activity distributions. These results indicate that
      the NEC is not only a measure for comparing the count rate performance of imaging
      systems. However, an absolute evaluation is impossible to depend on
      reconstruction algorithm, slice number, and phantom type.

PMID- 16957668
TI  - [Artifact of indicators equipped to stereotactic body frame scanned by 16-row
      MDCT can be resolved].
AB  - We found an artifact of the Stereotactic Body Frame's (SBF) indicators when we
      used diagnostic 16-row multi-detector computed tomography (MDCT) as a simulator.
      Stereotactic radiotherapy (SRT) requires the accuracy of each millimeter.
      However, a gap of 3 mm at the maximum along the Z axis was caused by this
      artifact. We assessed the characteristics and cause of this artifact and searched
      for an imaging parameter to reduce the artifact in SRT. It was considered that
      the artifact was formed mainly by a stair-step artifact and cone-beam artifact.
      We can acquired accuracy, 1 mm minimizing the beam width and pitch (10
      mm/0.5625). However, exposure time was extended because minimum pitch was
      selected. The influence on dose calculation was negligible. We decided to use a
      default parameter for treatment planning, and this parameter for determining the
      isocenter. We found the MDCT parameters to get acceptable positional accuracy for
      SRT with SBF.

PMID- 16957667
TI  - [Estimation of the effective dose of patient in interventional radiology: study
      of coronary angiography].
AB  - The applications of interventional radiology (IVR) increasingly are being used in
      clinical examinations, where they tend to extend examination time. In addition,
      the risk of occupational exposure necessarily is increasing with this technology.
      In this study, the dose distributions in a sliced acrylic-acid phantom involving
      the bore for each irradiation condition were measured using a thermoluminescence
      dosimeter (TLD). Four patterns of set-up for the fluoroscopy unit were chosen as
      references for the conditions generally used clinically. Exposure also was
      measured with dose area product (DAP), and we then calculated the entrance skin
      dose and effective dose for the patient. The results showed that the effective
      dose was 7.0 mSv to 8.0 mSv at LAO45 degrees and RAO30 degrees; 100 kV, 2.3 mSv
      to 3.3 mSv at LAO45 degrees and RAO30 degrees; 80 kV. The effective dose is
      greatly influenced by the setup of fluoroscopy in IVR. The change in DAP is
      especially influenced. We found that the relation between DAP and effective dose
      was corrected with the exponential function. The effective doses were not
      necessarily less than those of other radiation examinations, and increase. When
      PCI and TAE are repeated many times in IVR, we propose that the effective dose
      should be taken into consideration together with the skin dose for dose control
      management.

PMID- 16957669
TI  - [Differential dose albedo for high-energy X-rays on concrete slab].
AB  - We computed the differential dose albedo (alpha(D)) for high-energy X-rays on a
      concrete slab when the incident angle, reflection angle, and azimuth angle were
      changed, by means of Monte Carlo simulation. We found that alpha(D) changed with
      incident, reflection, and azimuth angles to the concrete slab. On the whole, the
      larger the incident angle, the larger alpha(D) tended to become. If the incident
      angle and reflection angle were the same, the larger the azimuth angle, the
      smaller alpha(D) tended to become. When the incident, reflection, and azimuth
      angles were the same, the smaller the X-ray energy was, the larger alpha(D)
      became, in the order of 10 MV, 6 MV, and 4 MV X-rays.

PMID- 16957670
TI  - Clinical advances in urogynecology.
AB  - Women with pelvic floor disorders can look forward to improved care with less
      morbidity over the next several years. Significant research efforts are underway
      to improve our understanding of an appropriate evaluation for women with all
      pelvic floor disorders, especially urinary incontinence and/or pelvic organ
      prolapse. More than ever before, research has contributed meaningful developments
      in treatment outcomes, including patient-reported outcomes. These advances have
      come largely due to the efforts of an increasing number of clinician-scientists,
      who design and conduct high-quality clinical trials. In addition, significant
      governmental resources have been committed to developing and supporting pelvic
      floor research networks. Population based research efforts have provided a broad
      understanding of the pelvic floor changes that women may experience over their
      lifetime, including an understanding of pelvic support over the decades. This
      work is augmented by the increasing number of studies that clarify the pelvic
      floor changes associated with pregnancy and delivery. In addition to learning
      more about basic pathophysiology, significant technical advances have occurred
      and have offered excellent treatment efficacy with reduced morbidity. New
      modalities of treatment are being evaluation, including botulinum toxin, for
      women with refractory urge incontinence due to detrusor overactivity. This work
      has been facilitated by the efforts of multidisciplinary teams composed of a
      widening group of pelvic floor specialists, including radiologists,
      physiotherapists and gastrointestinal specialists. A small, but extremely
      important, group of basic science investigators are contributing knowledge about
      pathophysiology using animal models, material testing and analyses of native
      tissue structures. The clinical advances in urogynecology are on a steep uprise
      and can be expected to significantly improve the well-being of women who suffer
      from pelvic floor disorders.

PMID- 16957671
TI  - Female stress urinary incontinence: review of the current literature.
AB  - Urinary incontinence is a prevalent problem that affects women of all ages. We
      reviewed the pathophysiology, evaluation, and treatment of stress urinary
      incontinence. We performed a comprehensive review of the literature using MEDLINE
      and resources cited in those peer-reviewed manuscripts. The results are
      presented. Stress urinary incontinence is defined as leakage of urine that occurs
      with a sudden increase in intra-abdominal pressure, such as that seen with
      physical activity, without concomitant rise in detrusor (bladder-generated)
      pressure. It is a prevalent and costly problem that affects women worldwide.
      Proper and thorough evaluation is imperative in order to provide patients with
      appropriate treatment options and accurate counseling regarding the risks,
      benefits, and alternatives to the available therapies. Numerous new techniques
      have been developed in the treatment of stress incontinence, and the approaches
      continue to evolve. With the increasing number of patients seeking treatment for
      stress incontinence, it is essential to stay current with the latest concepts in
      the mechanism of stress incontinence and the techniques available for its
      treatment. An overview of the latest literature and principles is presented.

PMID- 16957672
TI  - The current use of neuromodulation for bladder dysfunction.
AB  - Neuromodulation utilizes electrical stimulation to alter the function of an
      organ. Recent advances in technology and improved knowledge of micturition
      physiology have coincided with the growth of neuromodulation for the treatment of
      urinary urgency/frequency, urge incontinence and non-obstructive urinary
      retention. Currently, the most common modality for bladder neuromodulation
      involves stimulation through the S3 foramen, or sacral neuromodulation. This
      review will highlight the current indications, patients selection, implantation
      options/techniques, outcomes and complications of sacral neuromodulation. In
      addition, other methods of neuromodulation will be discussed.

PMID- 16957673
TI  - Recent advances in contraception.
AB  - The world population is expected to increase by 2.6 billion to 9.1 billion in
      2050. This will occur, if fertility decreases from today's 2.6 children to about
      2 children per woman. If fertility were to remain at the present level, 34
      million persons would be added annually by mid-century and thus the world
      population would reach 10.6 billion by 2050. The most notable increase in the
      world population will occur in third world countries. Therefore immense
      investments are being made to develop safe, reliable and easily used
      contraceptive methods. It has not proven easy. Further, acceptance of the methods
      has been called into question. And even their distribution would be very
      difficult although Population Council and organizations like it have put a lot of
      effort into that matter also. In addition, the methods should preferably be such
      that they could to some extent prevent the rapid spread of sexually transmitted
      infections. So, the task is not easy, but every effort must be made on this
      question also at governmental and international political levels. It is
      noteworthy that this kind of approach has been given more currency since the
      beginning of this millennium.

PMID- 16957674
TI  - [Risk factors for fetal and neonatal brain injury].
AB  - Epidemiological studies have suggested a strong association of fetal and neonatal
      brain damage with fetal infections and free radical release. Intrauterine
      infection and hypoxia ischemia appear to share some characteristics, including
      high levels of cytokines and adhesion molecules. The relevance of the actions of
      cytokines to a variety of neurological disorders has opened a potentially
      fruitful area of research and therapeutic development.

PMID- 16957675
TI  - [Haemocoagulative modifications correlated with pregnancy].
AB  - AIM: The aim of this paper was to establish the physiologic changes in the
      coagulation and fibrinolytic systems during normal pregnancy. METHODS: One
      hundred and twenty normal pregnant women were investigated in a longitudinal
      study involving 3 measurements: blood samples were collected at 12, 24 and 36
      weeks of gestation and were assayed for prothrombin time, antithrombin III
      (ATIII) activity, protein C activity, protein S (PS) activity, prothrombin
      fragments 1+2, type 1 plasminogen activator inhibitor activity, tissue
      plasminogen activator antigen, plasminogen, activated protein C resistance,
      factors VII and VIII levels and D dimer. Student t-test, one way analysis of
      variance (ANOVA) and Fisher test were used for statistical analysis. RESULTS:
      Factor VII and factor VIII were always increased with respect to controls.
      Variance analysis showed a statistically significant reduction for anticoagulants
      (PS) and a rise for F1+2 and D dimer. With regard to fibrinolysis, there was an
      increase both for t-PA and PA1-1 during pregnancy. Moreover, the increased
      activity of factors of haemostasis was accompanied by an increase of activity and
      concentration of ATIII and acquired activated protein C resistance. CONCLUSIONS:
      These findings suggest that normal pregnancy is associated with an
      hypercoagulable state, resulting into a moderate risk for thrombosis during the
      different trimesters of pregnancy. Also broad spectrum assays which measure a
      range of trombin/fibrin formation in serum have become an established mean to
      identify activation of blood coagulation and/or fibrinolysis. There is a
      considerable interest in the application of these assays to the diagnosis of
      other acquired hypercoagulable states; such as thrombophilia during pregnancy.
      From the viewpoint of coagulation/fibrinolysis changes, the follow-up of
      thrombophilia markers could be recommended when levels of coagulation parameters
      exceed the normal values during pregnancy.

PMID- 16957676
TI  - Soy isoflavones, lactobacilli, Magnolia bark extract, vitamin D3 and calcium.
      Controlled clinical study in menopause.
AB  - AIM: Affective and behavioural disorders possibly concomitant to the vasomotor
      menopausal symptoms worsen quality of life. A rational formulation containing soy
      isoflavones (60 mg), lactobacilli (500 millions spores), calcium (141 mg) and
      vitamin D3 (5 microg) was added of Magnolia bark extract (60 mg) and magnesium
      (50 mg) (Estromineral serena, ES). The Magnolia extract active principles
      interact with GABA system and exhibit a sedative central action. Magnesium
      intervenes in enzymatic reactions of the energetic metabolism and protects the
      bone integrity. Aim of this controlled study was to compare the clinical activity
      and safety of ES versus calcium+vitamin D3 (Ca+D) in menopause. METHODS: A
      controlled, randomised, multicentre study was carried out in symptomatic
      menopausal women with sleep or mood alterations. Women received 1 tablet/day of
      ES or Ca+D for 24 weeks. Symptoms during the treatment and final judgements on
      efficacy and acceptability were evaluated. RESULTS: Eighty-nine women (44 ES and
      45 Ca+D, mean age 53.8 years, in menopause since 56.6 months) participated to the
      study. Flushing, nocturnal sweating, palpitations, insomnia, asthenia, anxiety,
      mood depression, irritability, vaginal dryness, dyspareunia, and libido loss,
      significantly decreased in severity and frequency during ES versus Ca+D treatment
      even since the fourth week. Woman wellbeing (good/very good 66.7% vs 20%)
      judgement on efficacy (72.7% vs 17.1%) and acceptability (93.9% vs 31.4%) were
      significantly better for ES. CONCLUSIONS: The controlled study showed the
      efficacy of Magnolia extract and magnesium on psycho-affective and sleep
      disturbances in menopause, in addition to the effects of isoflavones on vasomotor
      symptoms. A global natural approach to menopause with ES evidenced its
      therapeutic usefulness and safety.

PMID- 16957677
TI  - Tibolone in the treatment of menopause: compliance, efficacy and safety in a ten
      year experience.
AB  - AIM: To assess tibolone compliance, efficacy and safety in everyday clinical
      practice a non-randomized, prospective, cohort clinical study was carried out.
      METHODS: One hundred and fifty post-menopausal women aged 48 to 73 years were
      prescribed tibolone: 72 of them were treated for 36.4 months, 55 terminated
      treatment after less than 1 year, while 23 never took the tablets after seeking
      for menopause counseling and having agreed upon the treatment. We examined:
      endometrial thickness and histology, total cholesterol, triglycerides,
      fibrinogen, AST, ALT, gamma-gt, and the body weight. RESULTS: Side effects were
      the main causes of withdrawal (32%), and insufficient therapeutic effect and
      adverse events for a small number of cases (5.5% and 4.7% respectively), while
      various causes (fear of cancer, missing tablets, family doctor or other
      specialist's advice, remission of symptoms) were responsible for terminating
      treatment after extended periods. Laboratory findings showed a favorable trend;
      only the (GT showed slightly higher mean values, although within a normal range.
      On average, weight during treatment increased of 1.5 kg, and endometrial
      thickness grew of 1.3 mm in a mean time of 34.5 months of observation. An average
      of 2.3%/year increase of bone mineral density was reported, though bone mass
      didn't improve in some patients. CONCLUSIONS: Different causes of terminating
      treatment are related to the length of treatment, side effects being the main
      reason for early withdrawals, efficacy on symptoms or medical advice or fear of
      treatment for extended periods of time. Effectiveness on bone mass, safety as
      resulting from endometrial thickness and laboratory measures are confirmed. It is
      suggested to enhance follow-up accuracy and reinforce counseling as measures to
      improve compliance.

PMID- 16957679
TI  - Consensus meeting: monosodium glutamate - an update.
AB  - OBJECTIVE: Update of the Hohenheim consensus on monosodium glutamate from 1997:
      Summary and evaluation of recent knowledge with respect to physiology and safety
      of monosodium glutamate. DESIGN: Experts from a range of relevant disciplines
      received and considered a series of questions related to aspects of the topic.
      SETTING: University of Hohenheim, Stuttgart, Germany. METHOD: The experts met and
      discussed the questions and arrived at a consensus. CONCLUSION: Total intake of
      glutamate from food in European countries is generally stable and ranged from 5
      to 12 g/day (free: ca. 1 g, protein-bound: ca. 10 g, added as flavor: ca. 0.4 g).
      L-Glutamate (GLU) from all sources is mainly used as energy fuel in enterocytes.
      A maximum intake of 6.000 [corrected] mg/kg body weight is regarded as safe. The
      general use of glutamate salts (monosodium-L-glutamate and others) as food
      additive can, thus, be regarded as harmless for the whole population. Even in
      unphysiologically high doses GLU will not trespass into fetal circulation.
      Further research work should, however, be done concerning the effects of high
      doses of a bolus supply at presence of an impaired blood brain barrier function.
      In situations with decreased appetite (e.g., elderly persons) palatability can be
      improved by low dose use of monosodium-L-glutamate.

PMID- 16957680
TI  - Changing rates of genetic subtypes of Prader-Willi syndrome in the UK.
AB  - The genetically determined neurodevelopmental disorder, Prader-Willi syndrome
      (PWS), has two main genetic subtypes: a 15q11-q13 deletion affecting the
      paternally inherited chromosome 15 and chromosome 15 maternal uniparental disomy
      (mUPD) in which two maternal copies of chromosome 15 are inherited but no
      paternal copy. It has been accepted that these subtypes occur in approximately 70
      and 25% of cases, respectively. This is the first report of a greater proportion
      (50%) of those with PWS due to mUPD in children presently under 5 years living in
      the UK. Increasing maternal age at conception is likely to explain the changing
      proportions in this generation of mothers.

PMID- 16957681
TI  - The scale and nature of Viking settlement in Ireland from Y-chromosome admixture
      analysis.
AB  - The Vikings (or Norse) played a prominent role in Irish history but, despite
      this, their genetic legacy in Ireland, which may provide insights into the nature
      and scale of their immigration, is largely unexplored. Irish surnames, some of
      which are thought to have Norse roots, are paternally inherited in a similar
      manner to Y-chromosomes. The correspondence of Scandinavian patrilineal ancestry
      in a cohort of Irish men bearing surnames of putative Norse origin was examined
      using both slow mutating unique event polymorphisms and relatively rapidly
      changing short tandem repeat Y-chromosome markers. Irish and Scandinavian
      admixture proportions were explored for both systems using six different
      admixture estimators, allowing a parallel investigation of the impact of method
      and marker type in Y-chromosome admixture analysis. Admixture proportion
      estimates in the putative Norse surname group were highly consistent and detected
      little trace of Scandinavian ancestry. In addition, there is scant evidence of
      Scandinavian Y-chromosome introgression in a general Irish population sample.
      Although conclusions are largely dependent on the accurate identification of
      Norse surnames, the findings are consistent with a relatively small number of
      Norse settlers (and descendents) migrating to Ireland during the Viking period
      (ca. AD 800-1200) suggesting that Norse colonial settlements might have been
      largely composed of indigenous Irish. This observation adds to previous genetic
      studies that point to a flexible Viking settlement approach across North Atlantic
      Europe.

PMID- 16957682
TI  - A novel R486Q mutation in BMPR1B resulting in either a brachydactyly type
      C/symphalangism-like phenotype or brachydactyly type A2.
AB  - Heterozygous missense mutations in the serine-threonine kinase receptor BMPR1B
      result typically in brachydactyly type A2 (BDA2), whereas mutations in the
      corresponding ligand GDF5 cause brachydactyly type C (BDC). Mutations in the GDF
      inhibitor Noggin (NOG) or activating mutations in GDF5 cause proximal
      symphalangism (SYM1). Here, we describe a novel mutation in BMPR1B (R486Q) that
      is associated with either BDA2 or a BDC/SYM1-like phenotype. Functional
      investigations of the R486Q mutation were performed and compared with the
      previously reported BDA2-causing mutation R486W and WT BMPR1B. Overexpression of
      the mutant receptors in chicken micromass cultures resulted in a strong
      inhibition of chondrogenesis with the R486Q mutant, showing a stronger effect
      than the R486W mutant. To investigate the consequences of the BMPR1B mutations on
      the intracellular signal transduction, we used stably transfected C2C12 cells and
      measured the activity of SMAD-dependent and SMAD-independent pathways. SMAD
      activation after stimulation with GDF5 was suppressed in both mutants. Alkaline
      phosphatase induction showed an almost complete loss of activation by both
      mutants. Our data extend the previously known mutational and phenotypic spectrum
      associated with mutations in BMPR1B. Disturbances of NOG-GDF5-BMPR1B signaling
      cascade can result in similar clinical manifestations depending on the
      quantitative effect and mode of action of the specific mutations within the same
      functional pathway.

PMID- 16957683
TI  - Neurofibromatosis 1.
AB  - Neurofibromatosis 1 predisposes affected individuals to the development of benign
      and malignant tumours that are frequently disfiguring and difficult to manage.
      However, advances in molecular biology and the development of mouse models have
      facilitated our understanding of disease pathogenesis. Positron emission
      tomography has demonstrated that sophisticated imaging techniques have a role in
      diagnosing complex problems like malignant peripheral nerve sheath tumours, while
      the prospect of targeted therapies for Nf1 complications is tantalisingly close.

PMID- 16957684
TI  - Planetary science: bedrock formation at Meridiani Planum.
AB  - The Mars Exploration Rover Opportunity discovered sulphate-rich sedimentary rocks
      at Meridiani Planum on Mars, which are interpreted by McCollom and Hynek as
      altered volcanic rocks. However, their conclusions are derived from an incorrect
      representation of our depositional model, which is upheld by more recent Rover
      data. We contend that all the available data still support an aeolian and aqueous
      sedimentary origin for Meridiani bedrock.

PMID- 16957690
TI  - Energy shame.

PMID- 16957689
TI  - Beauties of synthesis.

PMID- 16957691
TI  - Five years on.

PMID- 16957694
TI  - Muslim council phases in lunar calendar.

PMID- 16957693
TI  - Safe passage.

PMID- 16957696
TI  - French confusion leaves Iranians locked out of meeting.

PMID- 16957697
TI  - When science and theology meet.

PMID- 16957695
TI  - Mix and match: the hunt for what makes us human.

PMID- 16957699
TI  - 'Ethical' stem-cell paper under attack.

PMID- 16957702
TI  - The farmyard drug store.

PMID- 16957705
TI  - Solar energy: a new day dawning? Silicon Valley sunrise.

PMID- 16957706
TI  - Solar energy: radiation nation.

PMID- 16957707
TI  - And finally...

PMID- 16957708
TI  - Author lists: specify who did what to aid assessment.

PMID- 16957709
TI  - Dogma, not faith, is the barrier to scientific enquiry.

PMID- 16957710
TI  - Refund fertility-treatment costs for donated embryos.

PMID- 16957711
TI  - Selling out on nature.

PMID- 16957716
TI  - Reflections on Wallace.

PMID- 16957717
TI  - Cancer biology: infectious tumour cells.

PMID- 16957719
TI  - Mathematics: controlling our errors.

PMID- 16957718
TI  - Fluid dynamics: turbulence lost in transience.

PMID- 16957720
TI  - Analytical chemistry: playing molecular tag.

PMID- 16957721
TI  - Organic chemistry: catalysts break symmetry.

PMID- 16957723
TI  - Nitrogen balance and Arctic throughflow.

PMID- 16957724
TI  - Developing space weathering on the asteroid 25143 Itokawa.
AB  - Puzzlingly, the parent bodies of ordinary chondrites (the most abundant type of
      meteorites) do not seem to be abundant among asteroids. One possible explanation
      is that surfaces of the parent bodies become optically altered, to become the S
      type asteroids which are abundant in the main asteroid belt. The process is
      called 'space weathering'-it makes the visible and near-infrared reflectance
      spectrum of a body darker and redder. A recent survey of small, near-Earth
      asteroids suggests that the surfaces of small S asteroids may have developing
      stages of space weathering. Here we report that a dark region on a small (550
      metre) asteroid-25143 Itokawa-is significantly more space-weathered than a nearby
      bright region. Spectra of both regions are consistent with those of LL5-6
      chondrites after continuum removal. A simple calculation suggests that the dark
      area has a shorter mean optical path length and about 0.04 per cent by volume
      more nanophase metallic iron particles than the bright area. This clearly shows
      that space-weathered materials accumulate on small asteroids, which are likely to
      be the parent bodies of LL chondrites. We conclude that, because LL meteorites
      are the least abundant of ordinary (H, L, and LL) chondrites, there must be many
      asteroids with ordinary-chondrite compositions in near-Earth orbits.

PMID- 16957725
TI  - Finite lifetime of turbulence in shear flows.
AB  - Generally, the motion of fluids is smooth and laminar at low speeds but becomes
      highly disordered and turbulent as the velocity increases. The transition from
      laminar to turbulent flow can involve a sequence of instabilities in which the
      system realizes progressively more complicated states, or it can occur suddenly.
      Once the transition has taken place, it is generally assumed that, under steady
      conditions, the turbulent state will persist indefinitely. The flow of a fluid
      down a straight pipe provides a ubiquitous example of a shear flow undergoing a
      sudden transition from laminar to turbulent motion. Extensive calculations and
      experimental studies have shown that, at relatively low flow rates, turbulence in
      pipes is transient, and is characterized by an exponential distribution of
      lifetimes. They also suggest that for Reynolds numbers exceeding a critical value
      the lifetime diverges (that is, becomes infinitely large), marking a change from
      transient to persistent turbulence. Here we present experimental data and
      numerical calculations covering more than two decades of lifetimes, showing that
      the lifetime does not in fact diverge but rather increases exponentially with the
      Reynolds number. This implies that turbulence in pipes is only a transient event
      (contrary to the commonly accepted view), and that the turbulent and laminar
      states remain dynamically connected, suggesting avenues for turbulence control.

PMID- 16957726
TI  - A class of non-precious metal composite catalysts for fuel cells.
AB  - Fuel cells, as devices for direct conversion of the chemical energy of a fuel
      into electricity by electrochemical reactions, are among the key enabling
      technologies for the transition to a hydrogen-based economy. Of several different
      types of fuel cells under development today, polymer electrolyte fuel cells
      (PEFCs) have been recognized as a potential future power source for zero-emission
      vehicles. However, to become commercially viable, PEFCs have to overcome the
      barrier of high catalyst cost caused by the exclusive use of platinum and
      platinum-based catalysts in the fuel-cell electrodes. Here we demonstrate a new
      class of low-cost (non-precious metal)/(heteroatomic polymer) nanocomposite
      catalysts for the PEFC cathode, capable of combining high oxygen-reduction
      activity with good performance durability. Without any optimization, the cobalt
      polypyrrole composite catalyst enables power densities of about 0.15 W cm(-2) in
      H2-O2 fuel cells and displays no signs of performance degradation for more than
      100 hours. The results of this study show that heteroatomic polymers can be used
      not only to stabilize the non-precious metal in the acidic environment of the
      PEFC cathode but also to generate active sites for oxygen reduction reaction.

PMID- 16957727
TI  - Enantioselective silyl protection of alcohols catalysed by an amino-acid-based
      small molecule.
AB  - Reliable, selective and environmentally friendly chemical transformations are
      crucial to the development of new therapeutics and the design of novel materials.
      Chiral catalysts that can be easily prepared and used to obtain organic molecules
      of high enantiomeric purity are critical to modern chemical synthesis. The
      development of protecting groups that shield reactive functionalities has also
      proved indispensable in the preparation of complex biologically active molecules.
      Here we present a chiral catalyst that promotes the enantioselective protection
      of a secondary alcohol as one of the most commonly used protected forms of an
      alcohol: a silyl ether. The catalyst is a small, simple molecule that can be
      prepared in three steps from commercial materials without the need for rigorously
      controlled conditions. Enantioselective silylations are performed with commercial
      silyl chlorides and produce yields of up to 96 per cent at an enantiomeric ratio
      of up to 98:2. Chiral catalysts for selective formation of commonly used
      protecting groups such as silyl ethers should significantly enhance the ability
      of chemical synthesis to deliver, in a more practical and efficient manner,
      important organic molecules.

PMID- 16957728
TI  - Methane bubbling from Siberian thaw lakes as a positive feedback to climate
      warming.
AB  - Large uncertainties in the budget of atmospheric methane, an important greenhouse
      gas, limit the accuracy of climate change projections. Thaw lakes in North
      Siberia are known to emit methane, but the magnitude of these emissions remains
      uncertain because most methane is released through ebullition (bubbling), which
      is spatially and temporally variable. Here we report a new method of measuring
      ebullition and use it to quantify methane emissions from two thaw lakes in North
      Siberia. We show that ebullition accounts for 95 per cent of methane emissions
      from these lakes, and that methane flux from thaw lakes in our study region may
      be five times higher than previously estimated. Extrapolation of these fluxes
      indicates that thaw lakes in North Siberia emit 3.8 teragrams of methane per
      year, which increases present estimates of methane emissions from northern
      wetlands (< 6-40 teragrams per year; refs 1, 2, 4-6) by between 10 and 63 per
      cent. We find that thawing permafrost along lake margins accounts for most of the
      methane released from the lakes, and estimate that an expansion of thaw lakes
      between 1974 and 2000, which was concurrent with regional warming, increased
      methane emissions in our study region by 58 per cent. Furthermore, the
      Pleistocene age (35,260-42,900 years) of methane emitted from hotspots along
      thawing lake margins indicates that this positive feedback to climate warming has
      led to the release of old carbon stocks previously stored in permafrost.

PMID- 16957729
TI  - Magma heating by decompression-driven crystallization beneath andesite volcanoes.
AB  - Explosive volcanic eruptions are driven by exsolution of H2O-rich vapour from
      silicic magma. Eruption dynamics involve a complex interplay between nucleation
      and growth of vapour bubbles and crystallization, generating highly nonlinear
      variation in the physical properties of magma as it ascends beneath a volcano.
      This makes explosive volcanism difficult to model and, ultimately, to predict. A
      key unknown is the temperature variation in magma rising through the sub-volcanic
      system, as it loses gas and crystallizes en route. Thermodynamic modelling of
      magma that degasses, but does not crystallize, indicates that both cooling and
      heating are possible. Hitherto it has not been possible to evaluate such
      alternatives because of the difficulty of tracking temperature variations in
      moving magma several kilometres below the surface. Here we extend recent work on
      glassy melt inclusions trapped in plagioclase crystals to develop a method for
      tracking pressure-temperature-crystallinity paths in magma beneath two active
      andesite volcanoes. We use dissolved H2O in melt inclusions to constrain the
      pressure of H2O at the time an inclusion became sealed, incompatible trace
      element concentrations to calculate the corresponding magma crystallinity and
      plagioclase-melt geothermometry to determine the temperature. These data are
      allied to ilmenite-magnetite geothermometry to show that the temperature of
      ascending magma increases by up to 100 degrees C, owing to the release of latent
      heat of crystallization. This heating can account for several common textural
      features of andesitic magmas, which might otherwise be erroneously attributed to
      pre-eruptive magma mixing.

PMID- 16957730
TI  - Interference among deleterious mutations favours sex and recombination in finite
      populations.
AB  - Sex and recombination are widespread, but explaining these phenomena has been one
      of the most difficult problems in evolutionary biology. Recombination is
      advantageous when different individuals in a population carry different
      advantageous alleles. By bringing together advantageous alleles onto the same
      chromosome, recombination speeds up the process of adaptation and opposes the
      fixation of harmful mutations by means of Muller's ratchet. Nevertheless,
      adaptive substitutions favour sex and recombination only if the rate of adaptive
      mutation is high, and Muller's ratchet operates only in small or asexual
      populations. Here, by tracking the fate of modifier alleles that alter the
      frequency of sex and recombination, we show that background selection against
      deleterious mutant alleles provides a stochastic advantage to sex and
      recombination that increases with population size. The advantage arises because,
      with low levels of recombination, selection at other loci severely reduces the
      effective population size and genetic variance in fitness at a focal locus (the
      Hill-Robertson effect), making a population less able to respond to selection and
      to rid itself of deleterious mutations. Sex and recombination reveal the hidden
      genetic variance in fitness by combining chromosomes of intermediate fitness to
      create chromosomes that are relatively free of (or are loaded with) deleterious
      mutations. This increase in genetic variance within finite populations improves
      the response to selection and generates a substantial advantage to sex and
      recombination that is fairly insensitive to the form of epistatic interactions
      between deleterious alleles. The mechanism supported by our results offers a
      robust and broadly applicable explanation for the evolutionary advantage of
      recombination and can explain the spread of costly sex.

PMID- 16957731
TI  - Evidence for complete denitrification in a benthic foraminifer.
AB  - Benthic foraminifera are unicellular eukaryotes found abundantly in many types of
      marine sediments. Many species survive and possibly reproduce in anoxic habitats,
      but sustainable anaerobic metabolism has not been previously described. Here we
      demonstrate that the foraminifer Globobulimina pseudospinescens accumulates
      intracellular nitrate stores and that these can be respired to dinitrogen gas.
      The amounts of nitrate detected are estimated to be sufficient to support
      respiration for over a month. In a Swedish fjord sediment where G.
      pseudospinescens is the dominant foraminifer, the intracellular nitrate pool in
      this species accounted for 20% of the large, cell-bound, nitrate pool present in
      an oxygen-free zone. Similarly high nitrate concentrations were also detected in
      foraminifera Nonionella cf. stella and a Stainforthia species, the two dominant
      benthic taxa occurring within the oxygen minimum zone of the continental shelf
      off Chile. Given the high abundance of foraminifera in anoxic marine
      environments, these new findings suggest that foraminifera may play an important
      role in global nitrogen cycling and indicate that our understanding of the
      complexity of the marine nitrogen cycle is far from complete.

PMID- 16957732
TI  - Unravelling the dynamics of RNA degradation by ribonuclease II and its RNA-bound
      complex.
AB  - RNA degradation is a determining factor in the control of gene expression. The
      maturation, turnover and quality control of RNA is performed by many different
      classes of ribonucleases. Ribonuclease II (RNase II) is a major exoribonuclease
      that intervenes in all of these fundamental processes; it can act independently
      or as a component of the exosome, an essential RNA-degrading multiprotein
      complex. RNase II-like enzymes are found in all three kingdoms of life, but there
      are no structural data for any of the proteins of this family. Here we report the
      X-ray crystallographic structures of both the ligand-free (at 2.44 A resolution)
      and RNA-bound (at 2.74 A resolution) forms of Escherichia coli RNase II. In
      contrast to sequence predictions, the structures show that RNase II is organized
      into four domains: two cold-shock domains, one RNB catalytic domain, which has an
      unprecedented alphabeta-fold, and one S1 domain. The enzyme establishes contacts
      with RNA in two distinct regions, the 'anchor' and the 'catalytic' regions, which
      act synergistically to provide catalysis. The active site is buried within the
      RNB catalytic domain, in a pocket formed by four conserved sequence motifs. The
      structure shows that the catalytic pocket is only accessible to single-stranded
      RNA, and explains the specificity for RNA versus DNA cleavage. It also explains
      the dynamic mechanism of RNA degradation by providing the structural basis for
      RNA translocation and enzyme processivity. We propose a reaction mechanism for
      exonucleolytic RNA degradation involving key conserved residues. Our three
      dimensional model corroborates all existing biochemical data for RNase II, and
      elucidates the general basis for RNA degradation. Moreover, it reveals important
      structural features that can be extrapolated to other members of this family.

PMID- 16957734
TI  - Ageing: balancing regeneration and cancer.

PMID- 16957735
TI  - Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a.
AB  - Stem-cell ageing is thought to contribute to altered tissue maintenance and
      repair. Older humans experience increased bone marrow failure and poorer
      haematologic tolerance of cytotoxic injury. Haematopoietic stem cells (HSCs) in
      older mice have decreased per-cell repopulating activity, self-renewal and homing
      abilities, myeloid skewing of differentiation, and increased apoptosis with
      stress. Here we report that the cyclin-dependent kinase inhibitor p16INK4a, the
      level of which was previously noted to increase in other cell types with age,
      accumulates and modulates specific age-associated HSC functions. Notably, in the
      absence of p16INK4a, HSC repopulating defects and apoptosis were mitigated,
      improving the stress tolerance of cells and the survival of animals in successive
      transplants, a stem-cell-autonomous tissue regeneration model. Inhibition of
      p16INK4a may ameliorate the physiological impact of ageing on stem cells and
      thereby improve injury repair in aged tissue.

PMID- 16957736
TI  - Structure of the insulin receptor ectodomain reveals a folded-over conformation.
AB  - The insulin receptor is a phylogenetically ancient tyrosine kinase receptor found
      in organisms as primitive as cnidarians and insects. In higher organisms it is
      essential for glucose homeostasis, whereas the closely related insulin-like
      growth factor receptor (IGF-1R) is involved in normal growth and development. The
      insulin receptor is expressed in two isoforms, IR-A and IR-B; the former also
      functions as a high-affinity receptor for IGF-II and is implicated, along with
      IGF-1R, in malignant transformation. Here we present the crystal structure at 3.8
      A resolution of the IR-A ectodomain dimer, complexed with four Fabs from the
      monoclonal antibodies 83-7 and 83-14 (ref. 4), grown in the presence of a
      fragment of an insulin mimetic peptide. The structure reveals the domain
      arrangement in the disulphide-linked ectodomain dimer, showing that the insulin
      receptor adopts a folded-over conformation that places the ligand-binding regions
      in juxtaposition. This arrangement is very different from previous models. It
      shows that the two L1 domains are on opposite sides of the dimer, too far apart
      to allow insulin to bind both L1 domains simultaneously as previously proposed.
      Instead, the structure implicates the carboxy-terminal surface of the first
      fibronectin type III domain as the second binding site involved in high-affinity
      binding.

PMID- 16957737
TI  - p16INK4a induces an age-dependent decline in islet regenerative potential.
AB  - The p16INK4a tumour suppressor accumulates in many tissues as a function of
      advancing age. p16INK4a is an effector of senescence and a potent inhibitor of
      the proliferative kinase Cdk4 (ref. 6), which is essential for pancreatic beta
      cell proliferation in adult mammals. Here we show that p16INK4a constrains islet
      proliferation and regeneration in an age-dependent manner. Expression of the
      p16INK4a transcript is enriched in purified islets compared with the exocrine
      pancreas, and islet-specific expression of p16INK4a, but not other cyclin
      dependent kinase inhibitors, increases markedly with ageing. To determine the
      physiological significance of p16INK4a accumulation on islet function, we
      assessed the impact of p16INK4a deficiency and overexpression with increasing age
      and in the regenerative response after exposure to a specific beta-cell toxin.
      Transgenic mice that overexpress p16INK4a to a degree seen with ageing
      demonstrated decreased islet proliferation. Similarly, islet proliferation was
      unaffected by p16INK4a deficiency in young mice, but was relatively increased in
      p16(INK4a)-deficient old mice. Survival after toxin-mediated ablation of beta
      cells, which requires islet proliferation, declined with advancing age; however,
      mice lacking p16INK4a demonstrated enhanced islet proliferation and survival
      after beta-cell ablation. These genetic data support the view that an age-induced
      increase of p16INK4a expression limits the regenerative capacity of beta-cells
      with ageing.

PMID- 16957739
TI  - The pathological response to DNA damage does not contribute to p53-mediated
      tumour suppression.
AB  - The p53 protein has a highly evolutionarily conserved role in metazoans as
      'guardian of the genome', mediating cell-cycle arrest and apoptosis in response
      to genotoxic injury. In large, long-lived animals with substantial somatic
      regenerative capacity, such as vertebrates, p53 is an important tumour suppressor
      -an attribute thought to stem directly from its induction of death or arrest in
      mutant cells with damaged or unstable genomes. Chemotherapy and radiation
      exposure both induce widespread p53-dependent DNA damage. This triggers
      potentially lethal pathologies that are generally deemed an unfortunate but
      unavoidable consequence of the role p53 has in tumour suppression. Here we show,
      using a mouse model in which p53 status can be reversibly switched in vivo
      between functional and inactive states, that the p53-mediated pathological
      response to whole-body irradiation, a prototypical genotoxic carcinogen, is
      irrelevant for suppression of radiation-induced lymphoma. In contrast, delaying
      the restoration of p53 function until the acute radiation response has subsided
      abrogates all of the radiation-induced pathology yet preserves much of the
      protection from lymphoma. Such protection is absolutely dependent on p19(ARF)--a
      tumour suppressor induced not by DNA damage, but by oncogenic disruption of the
      cell cycle.

PMID- 16957738
TI  - Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis
      during ageing.
AB  - Mammalian ageing is associated with reduced regenerative capacity in tissues that
      contain stem cells. It has been proposed that this is at least partially caused
      by the senescence of progenitors with age; however, it has not yet been tested
      whether genes associated with senescence functionally contribute to physiological
      declines in progenitor activity. Here we show that progenitor proliferation in
      the subventricular zone and neurogenesis in the olfactory bulb, as well as
      multipotent progenitor frequency and self-renewal potential, all decline with age
      in the mouse forebrain. These declines in progenitor frequency and function
      correlate with increased expression of p16INK4a, which encodes a cyclin-dependent
      kinase inhibitor linked to senescence. Ageing p16INK4a-deficient mice showed a
      significantly smaller decline in subventricular zone proliferation, olfactory
      bulb neurogenesis, and the frequency and self-renewal potential of multipotent
      progenitors. p16INK4a deficiency did not detectably affect progenitor function in
      the dentate gyrus or enteric nervous system, indicating regional differences in
      the response of neural progenitors to increased p16INK4a expression during
      ageing. Declining subventricular zone progenitor function and olfactory bulb
      neurogenesis during ageing are thus caused partly by increasing p16INK4a
      expression.

PMID- 16957742
TI  - An unusual cause of gross hematuria, improved by recumbency.

PMID- 16957743
TI  - Medullary sponge kidney.

PMID- 16957744
TI  - The glomerular filter: Biologic and genetic complexity.
AB  - The list of known genes that, when altered, cause proteinuric renal disease
      continues to increase. Recent mouse and human genetic studies, including that by
      Hasselbacher et al., are refocusing our attention on glomerular basement membrane
      components as critical to the barrier to protein filtration.

PMID- 16957745
TI  - Dialysis rationing in South Africa: a global message.
AB  - Dialysis rationing resulting from limited facilities and health-care personnel in
      low- and middle-income countries such as South Africa must be addressed on
      several fronts. Prevention of kidney disease is an essential long-term approach,
      but in the short term, it is necessary to increase access to dialysis and
      transplantation, and to seek ways to limit the 'brain drain' to the developed
      world.

PMID- 16957746
TI  - Is there a genotype-phenotype correlation in primary hyperoxaluria type 1?
AB  - There is ongoing debate about a genotype-phenotype correlation in patients with
      primary hyperoxaluria type 1 and specific AGXT mutations. However, other
      determinants like environmental factors or modifer genes may play a pivotal role
      in the heterogeneity of the disease. The report of Lorenzo and co-workers
      highlights this situation, presenting data of a whole population with just one
      specific AGXT mutation.

PMID- 16957748
TI  - Therapy with lamivudine and steroids in a patient with acute hepatitis B and
      rapidly progressive glomerulonephritis.

PMID- 16957754
TI  - Good news from MEDLINE--and how you can help us stay one step ahead.

PMID- 16957750
TI  - Is i.v. iron really superior in CKD patients not on dialysis?

PMID- 16957755
TI  - Gene expression profiling of thyroid tumors--clinical applicability.

PMID- 16957756
TI  - Levothyroxine dosage and the limitations of current bioequivalence standards.

PMID- 16957757
TI  - How effective is octreotide-LAR as a primary treatment for growth-hormone
      secreting tumors?

PMID- 16957758
TI  - Does warfarin increase the risk of osteoporotic fracture?

PMID- 16957759
TI  - How effective is biphasic insulin aspart in the treatment of adolescents with
      type 1 diabetes?

PMID- 16957760
TI  - Does the metabolic activity of metastatic thyroid carcinoma correlate with
      prognosis?

PMID- 16957761
TI  - How useful is autoantibody screening in adult-onset diabetes?

PMID- 16957762
TI  - Different definitions of the metabolic syndrome and risk for recurrent
      cardiovascular disease.

PMID- 16957763
TI  - The diagnosis and management of asymptomatic primary hyperparathyroidism.
AB  - Classical primary hyperparathyroidism--a disease of 'bones, stones, and psychic
      groans'--is a rarity in the US, although it is still seen in some parts of the
      world. Today, most patients with primary hyperparathyroidism are asymptomatic.
      This change in clinical profile is not merely because of improved detection
      techniques, and patients with primary hyperparathyroidism who lack symptoms, if
      left untreated, rarely develop the 'classical' features that were common
      previously. Indeed, currently available data suggest that there is, today, a
      disorder with different, yet characteristic, effects on the end-organs of the
      hyperparathyroid process. In this review, the features of the skeletal, renal,
      neuropsychologic, cardiovascular, and gastrointestinal manifestations of
      'asymptomatic' primary hyperparathyroidism will be discussed. The considerable
      body of data that has emerged since the recognition of the new clinical profile
      of primary hyperparathyroidism has allowed a reconsideration of standards of care
      for this disease. These data were reviewed and incorporated into new clinical
      guidelines at the 2002 NIH workshop on asymptomatic primary hyperparathyroidism.
      These recommendations highlight both what is known about the disease, and
      important areas that need investigation. Continued interest in the skeletal,
      cardiovascular, and neuropsychiatric manifestations of the disease, and
      therapeutic trials of medical approaches for its management, will further refine
      our current understanding, and could lead to additional modifications in the
      approach to patients with this common endocrine disorder.

PMID- 16957764
TI  - Mechanisms of disease: proatherogenic HDL--an evolving field.
AB  - It is well known that, in large populations, HDL-cholesterol levels are inversely
      related to the risk of atherosclerotic clinical events; however, in an
      individual, the predictive value of an HDL-cholesterol level is far from perfect.
      As a result, other HDL-associated factors have been investigated, including the
      quality and function of HDL in contradistinction to the level of HDL-cholesterol.
      Regarding their quality, HDL particles are highly heterogeneous and contain
      varying levels of antioxidants or pro-oxidants, which results in variation in HDL
      function. It has been postulated that HDL functions to promote reverse
      cholesterol transport. Recent studies support this role for HDL but also indicate
      that HDL is a modulator of systemic inflammation. In the absence of inflammation,
      HDL has a complement of antioxidant enzymes that work to maintain an anti
      inflammatory state. In the presence of systemic inflammation, these antioxidant
      enzymes can be inactivated and HDL can accumulate oxidized lipids and proteins
      that make it proinflammatory. Under these conditions the main protein of HDL,
      apolipoprotein A-I, can be modified by reactive oxygen species. This modification
      impairs the ability of HDL to promote cholesterol efflux by the ATP-binding
      cassette transporter A-1 pathway. Animal studies and small-scale human studies
      suggest that measures of the quality and novel functions of HDL might provide an
      improved means of identifying subjects at increased risk for atherosclerotic
      events, compared with the current practice of only measuring HDL-cholesterol
      levels. The quality and function of HDL are also attractive targets for emerging
      therapies.

PMID- 16957765
TI  - Mechanisms of disease: psychomotor retardation and high T3 levels caused by
      mutations in monocarboxylate transporter 8.
AB  - The actions and the metabolism of thyroid hormone are intracellular events that
      require the transport of iodothyronines across the plasma membrane. It is
      increasingly clear that this process does not occur by simple diffusion, but is
      facilitated by transport proteins. Only recently have iodothyronine transporters
      been identified at the molecular level, of which organic anion transporting
      polypeptide 1C1 and monocarboxylate transporter 8 (MCT8) deserve special mention,
      because of their high activity and specificity for iodothyronines. Organic anion
      transporting polypeptide 1C1 is almost exclusively expressed in brain
      capillaries, and may be crucial for the transport of the prohormone T4 across the
      blood-brain barrier. MCT8 is also expressed in the brain--in particular, in
      neurons--but also in other tissues. MCT8 seems to be especially important for the
      uptake of active hormone T3 into neurons, which is essential for optimal brain
      development. T3 is produced from T4 by type 2 deiodinase in neighboring
      astrocytes. Neurons express type 3 deiodinase, the enzyme that terminates T3
      activity. The SLC16A2 (formerly MCT8) gene is located on chromosome Xq13.2 and
      has recently been associated with a syndrome combining severe, X-linked,
      psychomotor retardation and high serum T3 levels. In over 20 families, where
      affected males have developed this syndrome, several mutations in MCT8 have been
      identified. The disease mechanism is thought to involve a defect in the neuronal
      entry of T3 and, therefore, in the action and metabolism of T3 in these cells.
      This defect results in impaired neurological development and a decrease in T3
      clearance.

PMID- 16957766
TI  - TSH-induced hyperthyroidism caused by a pituitary tumor.
AB  - BACKGROUND: A 45-year-old man presented with frontal headache and visual
      disturbances to our clinic. For the previous 5 years, he had been receiving
      treatment for long-lasting mild hyperthyroidism with antithyroid therapy, but
      therapy had not been carefully followed. During the last 2 years he had also
      complained of erectile dysfunction and loss of libido. On physical examination,
      he had a small goiter, normal skin, no Graves' ophthalmopathy, normal BMI, and
      reduced testis volume and pubic hair. INVESTIGATIONS: Serum levels of free T3 and
      T4, serum prolactin, testosterone, serum gonadotropins, insulin-like growth
      factor 1, adrenocorticotropic hormone, and cortisol were measured. MRI scan, TSH
      releasing hormone test, and T3 suppression test were carried out. Levels of
      pituitary glycoprotein hormone alpha-subunit and sex-hormone-binding protein were
      also measured. DIAGNOSIS: Hyperthyroidism caused by a mixed pituitary adenoma
      that secretes prolactin and TSH. MANAGEMENT: Trans-sphenoidal resection of the
      pituitary tumor. After surgery, T3 suppression test failed to completely suppress
      TSH secretion, which suggested a persistence of residual adenomatous cells.
      Hyperthyroidism and hypogonadism recurred after 5 years, therefore, treatment
      with lanreotide was initiated, and resulted in complete resolution of signs and
      symptoms of the disease.

PMID- 16957767
TI  - Gene therapy progress and prospects: the skin--easily accessible, but still far
      away.
AB  - Significant progress has been made in corrective gene therapy of inherited skin
      diseases. This includes advances in vector technology, targeted gene expression,
      gene replacement, and the availability of appropriate animal models for a variety
      of candidate diseases. In addition, an increased understanding of the uptake and
      trafficking mechanisms inside keratinocytes has evolved. Topical application
      facilitates DNA vaccination through the skin, albeit clinical benefits have not
      yet materialized. However, the translation into clinical trials has only been
      partially mastered. The latter and the control of immune responses represent
      challenges for the research community.

PMID- 16957768
TI  - Adenoviral expression of XIAP antisense RNA induces apoptosis in glioma cells and
      suppresses the growth of xenografts in nude mice.
AB  - The expression of inhibitor of apoptosis (IAP) family members contributes to the
      resistance of human cancers to apoptosis induced by radiotherapy and
      chemotherapy. We report that the infection of malignant glioma cells and several
      other tumor cell lines with adenoviruses encoding antisense RNA to X-linked IAP
      (XIAP) depletes endogenous XIAP levels and promotes global caspase activation and
      apoptosis. In contrast, non-neoplastic SV-FHAS human astrocytes and other non
      neoplastic cells express XIAP at very low levels and resist these effects of
      adenovirus-expressing XIAP antisense RNA (Ad-XIAP-as). Caspase inhibitors such as
      z-Val-Ala-DL-Asp(OMe)-fluoromethylketone (zVAD-fmk) delay caspase processing and
      XIAP depletion, suggesting that XIAP depletion results both from antisense
      mediated interference with protein synthesis and proteolytic cleavage by
      activated caspases. However, zVAD-fmk neither prevents nor delays cell death,
      indicating a caspase-independent pathway to cell death triggered by IAP
      depletion. Similarly, B-cell lymphoma-X(L) (BCL-X(L)) inhibits caspase activity,
      but fails to rescue from apoptosis. Loss of p65/nuclear factor-kappaB (NF-kappaB)
      protein and NF-kappaB activity is an early event triggered by Ad-XIAP-as and
      probably involved in Ad-XIAP-as-induced apoptosis. Finally, Ad-XIAP-as gene
      therapy induces cell death in intracranial glioma xenografts, prolongs survival
      in nude mice and may reduce tumorigenicity in synergy with Apo2L/TNF-related
      apoptosis-inducing ligand (TRAIL) in vivo. Altogether, these data define a
      powerful survival function for XIAP and reinforce its possible role as a
      therapeutic target in human glioma cells.

PMID- 16957769
TI  - Sustained phenotypic correction in a mouse model of hypoalphalipoproteinemia with
      a helper-dependent adenovirus vector.
AB  - We examined the efficacy and host response to the adenovirus (Ad)-mediated
      delivery of human apolipoprotein A-I (APOA1) gene to the liver of APOA1(-/-)
      mice. Administration of a first-generation vector (FGAd-AI) resulted in a
      transient appearance of APOA1 in plasma and induced an anti-APOA1 antibody titer,
      whereas treatment with a helper-dependent vector (HDAd-AI) resulted in sustained
      APOA1 expression without inducing an antibody titer. With these results, we
      studied the effects of FGAd vectors on APOAI expression by HDAd-AI vector. Co
      treatment with an FGAd vector inhibited HDAd-AI- mediated APOA1 expression
      independent of transgene cassettes, but only FGAd-AI induced a humoral response.
      Furthermore, APOA1 mRNA levels in mice co-treated with FGAd vectors were much
      lower than those expected from the vector copy number, suggesting that DNA of
      FGAd vectors interferes with the HDAd-AI vector's APOA1 promoter. A single
      treatment with an HDAd-AI vector produced a supraphysiological plasma APOA1 level
      that gradually declined to about half the normal human level over the course of 2
      years, associated with a plasma cholesterol level that is persistently higher
      than that in controls. This investigation provides the proof of principle that
      liver-directed HDAd gene delivery is effective for the long-term phenotypic
      correction of monogenic hypoalphalipoproteinemia.

PMID- 16957770
TI  - Distinct roles of doublecortin modulating the microtubule cytoskeleton.
AB  - Doublecortin is a neuronal microtubule-stabilising protein, mutations of which
      cause mental retardation and epilepsy in humans. How doublecortin influences
      microtubule dynamics, and thereby brain development, is unclear. We show here by
      video microscopy that purified doublecortin has no effect on the growth rate of
      microtubules. However, it is a potent anti-catastrophe factor that stabilises
      microtubules by linking adjacent protofilaments and counteracting their outward
      bending in depolymerising microtubules. We show that doublecortin-stabilised
      microtubules are substrates for kinesin translocase motors and for depolymerase
      kinesins. In addition, doublecortin does not itself oligomerise and does not bind
      to tubulin heterodimers but does nucleate microtubules. In cells, doublecortin is
      enriched at the distal ends of neuronal processes and our data raise the
      possibility that the function of doublecortin in neurons is to drive assembly and
      stabilisation of non-centrosomal microtubules in these doublecortin-enriched
      distal zones. These distinct properties combine to give doublecortin a unique
      function in microtubule regulation, a role that cannot be compensated for by
      other microtubule-stabilising proteins and nucleating factors.

PMID- 16957771
TI  - A novel function of DNA polymerase zeta regulated by PCNA.
AB  - DNA polymerase zeta (Polzeta) participates in translesion DNA synthesis and is
      involved in the generation of the majority of mutations induced by DNA damage.
      The mechanisms that license access of Polzeta to the primer terminus and regulate
      the extent of its participation in genome replication are poorly understood. The
      Polzeta-dependent damage-induced mutagenesis requires monoubiquitination of
      proliferating cell nuclear antigen (PCNA) that is triggered by exposure to
      mutagens. We show that Polzeta contributes to DNA replication and causes
      mutagenesis not only in response to DNA damage but also in response to
      malfunction of normal replicative machinery due to mutations in replication
      genes. These replication defects lead to ubiquitination of PCNA even in the
      absence of DNA damage. Unlike damage-induced mutagenesis, the Polzeta-dependent
      spontaneous mutagenesis in replication mutants is reduced in strains defective in
      both ubiquitination and sumoylation of Lys164 of PCNA. Additionally, studies of a
      PCNA mutant defective for functional interactions with Polzeta, but not for
      monoubiquitination by the Rad6/Rad18 complex demonstrate a role for PCNA in
      regulating the mutagenic activity of Polzeta separate from its modification at
      Lys164.

PMID- 16957772
TI  - Early presynaptic changes during plasticity in cultured hippocampal neurons.
AB  - Long-lasting increase in synaptic strength is thought to underlie learning. An
      explosion of data has characterized changes in postsynaptic (pstS) AMPA receptor
      cycling during potentiation. However, changes occurring within the presynaptic
      (prS) terminal remain largely unknown. We show that appearance of new release
      sites during potentiation between cultured hippocampal neurons is due to (a)
      conversion of nonrecycling sites to recycling sites, (b) formation of new
      releasing sites from areas containing diffuse staining for the prS marker Vesicle
      Associated Membrane Protein-2 and (c) budding of new recycling sites from
      previously existing recycling sites. In addition, potentiation is accompanied by
      a release probability increase in pre-existing boutons depending upon their
      individual probability. These prS changes precede and regulate fluorescence
      increase for pstS GFP-tagged-AMPA-receptor subunit GluR1. These results suggest
      that potentiation involves early changes in the prS terminal including remodeling
      and release probability increase of pre-existing synapses.

PMID- 16957773
TI  - Secretion of L-glutamate from osteoclasts through transcytosis.
AB  - Osteoclasts are involved in the catabolism of the bone matrix and eliminate the
      resulting degradation products through transcytosis, but the molecular mechanism
      and regulation of transcytosis remain poorly understood. Upon differentiation,
      osteoclasts express vesicular glutamate transporter 1 (VGLUT1), which is
      essential for vesicular storage and subsequent exocytosis of glutamate in
      neurons. VGLUT1 is localized in transcytotic vesicles and accumulates L
      glutamate. Osteoclasts secrete L-glutamate and the bone degradation products upon
      stimulation with KCl or ATP in a Ca2+-dependent manner. KCl- and ATP-dependent
      secretion of L-glutamate was absent in osteoclasts prepared from VGLUT1-/-
      knockout mice. Osteoclasts express mGluR8, a class III metabotropic glutamate
      receptor. Its stimulation by a specific agonist inhibits secretion of L-glutamate
      and bone degradation products, whereas its suppression by a specific antagonist
      stimulates bone resorption. Finally, it was found that VGLUT1-/- mice develop
      osteoporosis. Thus, in bone-resorbing osteoclasts, L-glutamate and bone
      degradation products are secreted through transcytosis and the released L
      glutamate is involved in autoregulation of transcytosis. Glutamate signaling may
      play an important role in the bone homeostasis.

PMID- 16957774
TI  - A homologue of the breast cancer-associated gene BARD1 is involved in DNA repair
      in plants.
AB  - hBRCA1 and hBARD1 are tumor suppressor proteins that are involved as heterodimer
      via ubiquitinylation in many cellular processes, such as DNA repair. Loss of
      BRCA1 or BARD1 results in early embryonic lethality and chromosomal instability.
      The Arabidopsis genome carries a BRCA1 homologue, and we were able to identify a
      BARD1 homologue. AtBRCA1 and the putative AtBARD1 protein are able to interact
      with each other as indicated by in vitro and in planta experiments. We have
      identified T-DNA insertion mutants for both genes, which show no visible
      phenotype under standard growth conditions and are fully fertile. Thus, in
      contrast to animals, both genes have no indispensable role during development and
      meiosis in plants. The two single as well as the double mutant are to a similar
      extent sensitive to mitomycin C, indicating an epistatic interaction in DNA
      crosslink repair. We could further demonstrate that in Arabidopsis BARD1 plays a
      prominent role in the regulation of homologous DNA repair in somatic cells.

PMID- 16957775
TI  - bZIP10-LSD1 antagonism modulates basal defense and cell death in Arabidopsis
      following infection.
AB  - Plants use sophisticated strategies to balance responses to oxidative stress.
      Programmed cell death, including the hypersensitive response (HR) associated with
      successful pathogen recognition, is one cellular response regulated by reactive
      oxygen in various cellular contexts. The Arabidopsis basic leucine zipper (bZIP)
      transcription factor AtbZIP10 shuttles between the nucleus and the cytoplasm and
      binds consensus G- and C-box DNA sequences. Surprisingly, AtbZIP10 can be
      retained outside the nucleus by LSD1, a protein that protects Arabidopsis cells
      from death in the face of oxidative stress signals. We demonstrate that AtbZIP10
      is a positive mediator of the uncontrolled cell death observed in lsd1 mutants.
      AtbZIP10 and LSD1 act antagonistically in both pathogen-induced HR and basal
      defense responses. LSD1 likely functions as a cellular hub, where its interaction
      with AtbZIP10 and additional, as yet unidentified, proteins contributes
      significantly to plant oxidative stress responses.

PMID- 16957776
TI  - Silencing by plant Polycomb-group genes requires dispersed trimethylation of
      histone H3 at lysine 27.
AB  - The plant Polycomb-group (Pc-G) protein CURLY LEAF (CLF) is required to repress
      targets such as AGAMOUS (AG) and SHOOTMERISTEMLESS (STM). Using chromatin
      immunoprecipitation, we identify AG and STM as direct targets for CLF and show
      that they carry a characteristic epigenetic signature of dispersed histone H3
      lysine 27 trimethylation (H3K27me3) and localised H3K27me2 methylation. H3K27
      methylation is present throughout leaf development and consistent with this, CLF
      is required persistently to silence AG. However, CLF is not itself an epigenetic
      mark as it is lost during mitosis. We suggest a model in which Pc-G proteins are
      recruited to localised regions of targets and then mediate dispersed H3K27me3.
      Analysis of transgenes carrying AG regulatory sequences confirms that H3K27me3
      can spread to novel sequences in a CLF-dependent manner and further shows that
      H3K27me3 methylation is not sufficient for silencing of targets. We suggest that
      the spread of H3K27me3 contributes to the mitotic heritability of Pc-G silencing,
      and that the loss of silencing caused by transposon insertions at plant Pc-G
      targets reflects impaired spreading.

PMID- 16957777
TI  - Dissection of the unusual structural and functional properties of the variant
      H2A.Bbd nucleosome.
AB  - The histone variant H2A.Bbd appeared to be associated with active chromatin, but
      how it functions is unknown. We have dissected the properties of nucleosome
      containing H2A.Bbd. Atomic force microscopy (AFM) and electron cryo-microscopy
      (cryo-EM) showed that the H2A.Bbd histone octamer organizes only approximately
      130 bp of DNA, suggesting that 10 bp of each end of nucleosomal DNA are released
      from the octamer. In agreement with this, the entry/exit angle of the nucleosomal
      DNA ends formed an angle close to 180 degrees and the physico-chemical analysis
      pointed to a lower stability of the variant particle. Reconstitution of
      nucleosomes with swapped-tail mutants demonstrated that the N-terminus of H2A.Bbd
      has no impact on the nucleosome properties. AFM, cryo-EM and chromatin remodeling
      experiments showed that the overall structure and stability of the particle, but
      not its property to interfere with the SWI/SNF induced remodeling, were
      determined to a considerable extent by the H2A.Bbd docking domain. These data
      show that the whole H2A.Bbd histone fold domain is responsible for the unusual
      properties of the H2A.Bbd nucleosome.

PMID- 16957778
TI  - The catalytic subunit of the proteasome is engaged in the entire process of
      estrogen receptor-regulated transcription.
AB  - The ubiquitin-proteasome system plays an important role in a variety of cellular
      functions by means of its proteolytic activity. Interestingly, recent studies
      have indicated that the proteasome components are also integral parts of
      transcription complexes. In genome-wide screening for steroid receptor
      coactivator (SRC)-interacting proteins using yeast two-hybrid system, we found
      that the 20S proteasome beta subunit LMP2 (Low Molecular mass Polypeptide 2)
      interacts directly with the SRC coactivators. We showed that LMP2 is required for
      estrogen receptor (ER)-mediated gene transcription and for estrogen-stimulated
      cell cycle progression. We found that LMP2-associated proteasome is recruited to
      the entire sequence of ER target genes, implicating a role for the proteasome in
      both transcription initiation and elongation. We demonstrated that the
      recruitment of LMP2 by SRC coactivators is necessary for cyclic association of ER
      regulated transcription complexes on ER targets. These results revealed a
      mechanism by which the proteasome machinery is recruited in ER-mediated gene
      transcription. Our experiments also provided evidence implicating SRC
      coactivators in gene transcription elongation.

PMID- 16957779
TI  - Hippocampal neurons recycle BDNF for activity-dependent secretion and LTP
      maintenance.
AB  - Regulation of brain-derived neurotrophic factor (BDNF) secretion plays a critical
      role in long-term potentiation (LTP). It is generally thought that the supply for
      this secretion is newly synthesized BDNF targeted to the synapse. Here we provide
      evidence that hippocampal neurons additionally recycle BDNF for activity
      dependent secretion. Exogenously applied BDNF is internalized by cultured neurons
      and rapidly becomes available for activity-dependent secretion, which is
      controlled by the same mechanisms that regulate the secretion of newly
      synthesized BDNF. Moreover, BDNF recycling replaced the new synthesis pathway in
      mediating the maintenance of LTP in hippocampal slices: the late phase LTP, which
      is abolished by protein synthesis inhibition, was rescued in slices preincubated
      with BDNF. Thus, endocytosed BDNF is fed back to the activity-dependent
      releasable pool required for LTP maintenance.

PMID- 16957782
TI  - Bis (pyridine) (2,3,12,13-tetrabromo-5, 10, 15, 20-tetraphenylporphyrin) iron
      (II) pyridine solvate.
AB  - The title compound, (C(44)H(24)Br(4)N(4))(C(5)H(5)N)(2)Fe.C(5)H(5)N, is located
      on a two-fold axis that passes through Fe and the pyridine ligands. Only slight
      asymmetry, 0.010 A elongation due to the Br substituents, is seen in the Fe-N(p)
      distances. The pyridine ligands are twisted 19.2 degrees  from each other.

PMID- 16957780
TI  - Antiviral action of the tumor suppressor ARF.
AB  - Oncogenic viruses frequently target the pathways controlled by tumor suppressor
      genes, suggesting an extra function for these proteins as antiviral factors. The
      control exerted by the tumor suppressor Arf on cellular proliferation is crucial
      to restrict tumor development; however, a potential contribution of Arf to
      prevent viral infectivity has remained unexplored. In the present study, we
      investigated the consequences of loss or increased expression of Arf on viral
      infection. Our results reveal that ARF expression is induced by interferon and
      after viral infection. Furthermore, we show that ARF protects against viral
      infection in a gene dosage-dependent manner, and that this antiviral action is
      mediated in part by PKR through a mechanism that involves ARF-induced release of
      PKR from nucleophosmin complexes. Finally, Arf-null mice were hypersensitive to
      viral infection compared to wild-type mice. Together, our results reveal a novel
      and unexpected role for the tumor suppressor ARF in viral infection surveillance.

PMID- 16957783
TI  - Psychometric utility of the childhood trauma questionnaire with female street
      based sex workers.
AB  - The present study examines the psychometric properties of a verbal, face-to-face
      administration of the Childhood Trauma Questionnaire (CTQ) with female street
      based sex workers (N = 171). Confirmatory Factor Analysis (CFA) indicated a poor
      fit between our data and the instrument's established 5-factor structure.
      Exploratory Factor Analysis (EFA) yielded four stable and usable factors
      corresponding to the Emotional Abuse, Emotional Neglect, Physical Abuse, and
      Sexual Abuse subscales of the CTQ; the Physical Neglect subscale did not emerge
      as a stable factor. Cross loading of many CTQ items onto more than one factor
      most likely produced the poor CFA fit, and indicated that abuse/neglect
      constructs were not conceptually distinct for our sample. Mean trauma scores did
      not differ significantly from published scores for female substance abusers.
      According to the CTQ Minimization/Denial scale, 42% of participants minimized
      their childhood maltreatment experiences. A combination of qualitative and
      quantitative methods may be optimal for the acquisition of sensitive trauma
      information with wary and vulnerable street populations.

PMID- 16957785
TI  - Fiber-reinforced composite substructure: load-bearing capacity of an onlay
      restoration and flexural properties of the material.
AB  - AIM: The aim of this study was to determine the static load-bearing capacity of
      composite resin onlay restorations made of particulate filler composite (PFC)
      with two different types of fiber-reinforced composite (FRC) substructures. In
      addition, flexural properties of the material combination and the effect of
      polymerization devices were tested. METHODS AND MATERIALS: Specimens were
      prepared to simulate an onlay restoration, which consisted of 2 to 3 mm of FRC
      layer as a substructure (short random and continuous bidirectional fiber
      orientation) and a 1 mm surface layer of PFC. Control specimens were prepared
      from plain PFC. In Group A the specimens were incrementally polymerized only with
      a hand-light curing unit for 40 s, while in Group B the specimens were post-cured
      in a light-curing oven for 15 min before they were statically loaded with a steel
      ball. Bar-shaped test specimens were prepared to measure the flexural properties
      of material combination using a three-point bending test (ISO 10477). RESULTS:
      Analysis of variance (ANOVA) revealed all specimens with a FRC substructure have
      higher values of static load-bearing capacity and flexural properties than those
      obtained with plain PFC (p<0.001). CONCLUSION: The load-bearing capacity of all
      the specimens decreased after post-curing and water storage. Restorations made
      from a material combination of FRC and PFC showed better mechanical properties
      than those obtained with plain PFC.

PMID- 16957786
TI  - Effect of different bonding conditions on the shear bond strength of two
      compomers to bovine dentin.
AB  - AIM: Despite the improvements to compomer materials, the bond strength of these
      materials remains inferior to "composite/resin bonding" systems and limits their
      clinical use. The purpose of this study was to evaluate the effect of acidic
      conditioning with phosphoric acid and Prompt L-Pop (PLP) on the shear bond
      strength of two compomers Dyract AP (DAP) and Composan Glass (CG) to dentin.
      METHODS AND MATERIALS: Sixty extracted bovine teeth were used to test the shear
      bond strength of two compomers to flat dentin labial surfaces. The dentin
      specimens were randomly assigned to six groups of ten specimens each: Group 1:
      DAP and Prime & Bond NT (PBNT); Group 2: DAP/PBNT with a 15 second dentin etch
      prior to bonding; Group 3: DAP placed with PLP adhesive; Group 4: CG and
      Compobond NE (CBNE); Group 5: CG/CBNE with a 15 second dentin etch; and Group 6:
      CG placed with PLP adhesive. The specimens were stored at 37 masculineC with 100%
      humidity for 24 hours then mounted and sheared using an Instron Universal Testing
      Machine at a cross head speed of 0.5 mm/min. The results were recorded in Mega
      Pascals (MPa). The sheared specimens were examined under a light microscope, and
      the type of failure (adhesive, cohesive, or mixed) was recorded. RESULTS: The
      mean dentin shear bond strength value (MPa) for the groups was: Group 1 (11.6+/
      3.9); Group 2 (13.2+/-3.3); Group 3 (12.4+/-2.0); Group 4 (13.0+/-4.3); Group 5
      (19.3+/-3.7); and Group 6 (13.1+/-3.0). One way analysis of variance (ANOVA) and
      Tukey HSD post-hoc tests detected a significantly higher bond strength (P =
      0.003) for group 5. For groups 1, 3, 4, and 6, the mode of failure was mostly
      adhesive. When acid etching of dentin was performed (groups 2 and 5), cohesive
      fracture within dentin was the predominant mode of failure. Acid etching and the
      use of PLP significantly reduced the number of adhesive fractures and reduced
      variability in the shear bond strength results. CONCLUSIONS: Acid etching
      significantly increased the shear bond strength of CG to dentin but did not
      affect DAP. The application of PLP resulted in a shear bond strength not
      statistically different from PBNT or CPNE. CG bond to dentin is improved with
      acid etching using phosphoric acid. However, PLP provided no significant
      improvement in the shear bond strength of DAP and CG.

PMID- 16957781
TI  - New functions of XPC in the protection of human skin cells from oxidative damage.
AB  - Xeroderma pigmentosum (XP) C is involved in the recognition of a variety of bulky
      DNA-distorting lesions in nucleotide excision repair. Here, we show that XPC
      plays an unexpected and multifaceted role in cell protection from oxidative DNA
      damage. XP-C primary keratinocytes and fibroblasts are hypersensitive to the
      killing effects of DNA-oxidizing agents and this effect is reverted by expression
      of wild-type XPC. Upon oxidant exposure, XP-C primary keratinocytes and
      fibroblasts accumulate 8,5'-cyclopurine 2'-deoxynucleosides in their DNA,
      indicating that XPC is involved in their removal. In the absence of XPC, a
      decrease in the repair rate of 8-hydroxyguanine (8-OH-Gua) is also observed. We
      demonstrate that XPC-HR23B complex acts as cofactor in base excision repair of 8
      OH-Gua, by stimulating the activity of its specific DNA glycosylase OGG1. In
      vitro experiments suggest that the mechanism involved is a combination of
      increased loading and turnover of OGG1 by XPC-HR23B complex. The accumulation of
      endogenous oxidative DNA damage might contribute to increased skin cancer risk
      and account for internal cancers reported for XP-C patients.

PMID- 16957787
TI  - The effect of adding a stone base on the accuracy of working casts using
      different types of dental stone.
AB  - AIM: Gypsum products are used for the preparation of stone casts of oral and
      maxillofacial structures and as important adjuncts to dental laboratory
      operations involved in the production of dental prostheses. The aim of this study
      was to determine the effect on the dimensional accuracy of a working cast of
      adding a stone base using different stone products. METHODS AND MATERIALS: A
      total of forty impressions of a mandibular dentoform were made. The impressions
      were dried with compressed air and stored at room temperature for 24 hours before
      pouring stone casts. The forty impressions were randomly divided into four groups
      of ten each. All forty impressions were poured once using one pre-weighed 140 Gm
      package of Silky Rock (SR) Type IV improved stone (Whip Mix Corporation,
      Louisville, KY, USA ) per impression. All working casts and the die setups were
      prepared according to the manufacturer's recommendations for pin placement (M.R.
      Dual pin and sleeve). Four different types of dental stone (II, III, and IV) and
      Flow Stone (FS) were used as bases for the working models. They were mixed
      according to the manufacturer's recommendations. The lower posterior teeth were
      flattened on the dentoform prior to taking the impressions. All were indexed
      using a mounted abrasive disc. Four teeth were selected as follows: 21, 28, 30,
      and 18. These represented A, B, C, and D landmarks, respectively. All
      measurements (five times for each specimen) were made with a Universal measuring
      microscope (Unitron Instruments, Inc., Bohemia, NY, USA). After the pre-sectioned
      measurements were recorded, the stone base was poured. A manual hand saw was used
      to section and fabricate removable dies for the mandibular landmarks A, B, C, and
      D. The dies were later seated and removed ten times to simulate the average
      amount of handling during laboratory procedures. Each die was carefully seated
      and measurements were made using the same technique as for the master model and
      unsectioned casts. Multivariate repeated measures analysis of variance (MANOVA)
      was used to test the difference in three different landmark distances (AB, AC,
      and AD) among the master model before and after sectioning of the working dies
      and among the four different base materials. Univariate analysis of variance
      (ANOVA) was conducted for each measurement, AB, AC, and AD to test the difference
      in landmark distances on the master model at pre sectioning and then at post
      sectioning using four different base materials. When there was a significant main
      effect (p < .05), the Student-Newman-Keul's (SNK) were used to test for pair wise
      comparison of means (P<0.05). RESULTS: The results of the MANOVA indicated there
      was a significant difference in three landmark measurements on the master model
      before and after sectioning of the working dies for the four different base
      materials (F = 6.60, p = 0.0001). In addition there was a significant difference
      in three landmark measurements on the master model at: (1) pre sectioning (p =
      0.0001), (2) between the master model and SR material (p = 0.0002), (3) between
      the master model and Laboratory Plaster (LP) material (p = 0.0001), (4) between
      the master model and Quick Stone (QS) material (p = 0.0001), and (5) between the
      master model and FS material (p = 0.0001).

PMID- 16957788
TI  - Radiographic assessment of post-retained crowns in an adult Jordanian population.
AB  - AIM: The objective of this study was to radiographically assess and compare the
      quality of post-retained crowns fabricated at the Dental Health Centre of the
      Jordan University of Science & Technology (JUST). METHODS AND MATERIALS: Study
      data were collected in 2002 from existing dental records for all patients
      receiving treatment with post-retained crowns between October, 1997 and June,
      1999. The posts were assessed radiographically to evaluate various aspects of the
      quality of post-retained crowns. All 129 posts were fabricated in the dental
      school. RESULTS: The most-frequently restored teeth were the maxillary incisors
      (38.8%). Sixty-two percent of the posts were tapered, while 38% were parallel
      sided. The mean length of the posts was 0.95 mm (SD 0.41) with a range between
      0.22-2.85 mm. Caries was diagnosed radiographically in 10.8% of cases with
      lesions located on root surfaces in 64.3% of them, while 35.7% of lesions were
      within the root canal. Three posts (2.3%) were deviated from the line of the root
      canal in the mesio-distal plane. No evidence of root filling was found in 2.3% of
      the cases. In the remainder of teeth 15.5% had gutta percha extended to the
      radiographic apex of the tooth, while 59.7% fell 0.5-1 mm short of the
      radiographic apex. Gutta-percha was extruded beyond the apex in 22.5% of the
      teeth. Space between the end of the post and the root filling was found in 22.2%.
      The percentage of canals with apparently completely healthy periapical tissue was
      51.2%. In the rest of the cases 34.8% had areas of radiolucency at or near the
      root apices and 14% demonstrated widening of the periodontal space around the
      root apex. Root resection had been completed in 2.3% cases. Signs of external
      resorption were apparent in one case (0.78%). CONCLUSION: The standards of the
      treatment of the endodontically treated teeth made at the dental hospital were
      satisfactory but could be improved by a controlled academic supervisory
      environment and a strict scientific approach to fixed prosthodontics within the
      dental school.

PMID- 16957789
TI  - Viability of human periodontal ligament fibroblasts in tissue culture after
      exposure to different contact lens solutions.
AB  - AIM: The viability of the periodontal ligament (PDL) cells is critical for
      successful healing of replanted avulsed teeth. Viability is primarily dependent
      on the duration of the extra-alveolar time and storage medium used to preserve
      teeth. Several storage media have been suggested but milk ranks highest. It would
      be desirable to evaluate other media as a suitable alternative for milk. The
      purpose of this study was to determine the viability of human PDL fibroblasts and
      their morphology after storage in different types of contact lens solutions.
      METHODS AND MATERIALS: PDL fibroblasts were cultured from a healthy extracted
      impacted human tooth and exposed to Bausch and Lomb (Renu), Ciba Vision (Titmus),
      and Alcon (Opti-free) contact lens solutions. Eagle's minimal essential medium
      served as control. The experiment was performed in plastic tissue culture
      clusters containing 24 wells. The PDL fibroblasts were grown in each well for
      three days. On the day of the experiment the culture medium was decanted, the
      cells were washed with phosphate buffered saline solution (PBS), and 1 ml of the
      tested solution was placed in each culture well. All tissue culture clusters were
      incubated at 37 degrees C in 5% CO2 and 95% air for one, four, and 24 hrs. At the
      end of the incubation period, the cells were fixed and prepared for scanning
      electron microscope (SEM) examination. RESULTS: The results indicated Renu and
      Opti-free solutions were superior to Titmus solution in terms of their capacity
      to maintain the viability and normal morphology of PDL fibroblasts. CONCLUSION:
      Contact lens solution is a good storage medium to maintain the viability of PDL
      fibroblasts for a short-term period.

PMID- 16957790
TI  - Apical leakage of Resilon obturation material.
AB  - AIM: The aim of this study was to assess the apical sealing ability of Resilon
      obturation material. METHODS AND MATERIALS: Forty-two single rooted extracted
      human teeth were selected and randomly divided into three groups. They were
      obturated using lateral condensation with gutta-percha and AH 26/AH plus and
      Resilon; also, 12 root canals were used as control groups. The apical leakage was
      measured using the dye penetration methodology. RESULTS: The teeth filled with
      gutta-percha and AH 26 displayed the most apical leakage. The least apical
      leakage was shown with Resilon. DISCUSSION: The differences in leakage among the
      groups, gutta-percha with AH 26 (2.4 mm, SD:1.87), gutta-percha with AH plus (2.1
      mm, SD: 1.69), and Resilon (1.7 mm, SD:1.32), were statistically significant (p<
      0.001). CONCLUSION: Based on the data of this study, all groups produced a
      satisfactory seal. However, Resilon and Epiphany sealer showed the least apical
      leakage.

PMID- 16957791
TI  - Antimicrobial efficiency of some antiseptic products on endodontic microflora
      isolated from gangrenous pulp tissue.
AB  - AIM: The aims of the study are to investigate the bactericidal effect of three
      antiseptics (chlorhexidine solution, povidone-iodine solution, and Walkhoff
      solution) and to determine the minimum inhibitory concentration and their effect
      on different microbial species. METHODS AND MATERIALS: The study was performed on
      microflora derived from root canals with simple and complicated pulp gangrene and
      on pure strains of Enterococcus and Candida albicans. RESULTS: Chlorhexidine and
      povidone-iodine proved to have antibacterial and antifungal effects if used in
      the treatment of pulp gangrene and in cases not responding to conventional
      therapy. CONCLUSION: According to the obtained results, the spectrum of
      antibacterial agents used in infected canal irrigation can be enlarged to include
      the agents tested.

PMID- 16957792
TI  - Dental development in subjects with thalassemia major.
AB  - AIM: The aim of this study was to evaluate the dental development of patients
      with ss-thalassemia major and to compare it with unaffected children. METHODS AND
      MATERIALS: Panoramic radiographs of 44 thalassemic patients taken before the age
      of 16 years were examined. The subjects consisted of 29 males and 15 females
      ranging in age from 4.9 to 15.7 (mean = 10.8+/-2.9) years and 44 controls matched
      for age and sex. The seven left mandibular permanent teeth, second molar to
      central incisor, were rated on an eight stage scale using the methods described
      by Demirjian et al.10 The stage of each tooth was converted to the corresponding
      numeric value and then all values were added to obtain a dental maturity score
      which corresponded to a dental age. Dental and chronologic ages were compared
      using a paired t-test. The relationship between the chronologic age and the
      amount of delay was also determined. RESULTS: Thirty-nine patients had a delay in
      the development of their dentition. The mean developmental dental delay was found
      to be 1.01 years (p<0.05). The range in delay was from 0.1 to 2.9 years. There
      was no significant difference between the mean chronologic and dental age of the
      control group (p> 0.05). The amount of delay in dental development increases as
      the patient's age increased (p<0.05). Males were found to have a greater delay
      (mean 1.16 years) than females (mean delay 0.73 years), but this difference was
      not statistically significant. CONCLUSIONS: The delay in dental development in ss
      thalassemia major varied according to the patient's age. This positive
      correlation parallels the general growth of thalassemic children.

PMID- 16957793
TI  - Prevalence, intensity, and correlation of different TMJ symptoms in Lebanese and
      Italian subpopulations.
AB  - AIM: The aim of this study was to compare self reported joint related
      temporomandibular disorder (TMD) symptoms in Lebanese and Italian dental and non
      dental students and to detect any correlation between different symptoms. METHODS
      AND MATERIALS: A questionnaire was distributed in Sardinia (Italy) to dental and
      psychology students and in Lebanon to dental, physical therapy, and biology
      students to investigate the prevalence, intensity, and correlation of four
      temporomandibular joint (TMJ) symptoms. RESULTS: Prevalence of earache varied
      among the groups from 10.1% to 29.2%, ear stuffiness from 22.5% to 30.8%, TMJ
      pain from 13.2% to 21.2%, and TMJ sounds from 18.4% to 46.2%. DISCUSSION:
      Different prevalence and intensity of earache and TMJ sounds were found in the
      examined sub-populations diverse in cultural background and education. However,
      prevalence and intensity of ear stuffiness and TMJ pain were similar. Association
      between TMJ sounds and TMJ pain was detected in selected sub-populations, and
      correlation between one symptom on one side of the head with the same symptom on
      the contralateral side were noted suggesting most of these symptoms are
      bilateral. CONCLUSION: The results of the study might be useful to anticipate the
      possible occurrence of associated symptoms or the same symptom on both sides of
      the head. Correlations with cultural background and education are difficult to
      establish.

PMID- 16957794
TI  - A review of polymerization shrinkage stress: current techniques for posterior
      direct resin restorations.
AB  - In general excellent results cannot be guaranteed when using resin-based
      composites for posterior restorations. This is due to polymerization shrinkage
      which can still be regarded as the primary negative characteristic of composite
      resins. A review of available literature regarding the polymerization process,
      its flaws, and suggested strategies to avoid shrinkage stress was conducted.
      Several factors responsible for the polymerization process may negatively affect
      the integrity of the tooth-restoration complex. There is no straightforward way
      of handling adhesive restorative materials that can guarantee the reliability of
      a restoration. At present, the practitioner has to coexist with the problem of
      polymerization shrinkage and destructive shrinkage stress. However, evolving
      improvements associated with resin-based composite materials, dental adhesives,
      filling, and light curing techniques have improved the predictability of such
      restorations. This critical review paper is meant to be a useful contribution to
      the recognition and understanding of problems related to polymerization shrinkage
      and to provide clinicians with the opportunity to improve the quality of
      composite resin restorations.

PMID- 16957795
TI  - Traumatic pseudolipoma of the oral cavity: report of a case.
AB  - An uncommon traumatic pseudolipoma of the oral cavity is presented. In this
      particular case there was evidence of previous trauma to the buccal fat pad
      during a difficult extraction of a maxillary premolar. Evidence is presented that
      iatrogenic trauma resulting in foreign body introduction might produce traumatic
      pseudolipoma in the oral cavity. The morphology of the buccal fat pad, the
      possible pathogenisis of the condition, as well as the diagnostic and the
      management of the case are presented.

PMID- 16957796
TI  - Bilaterally impacted maxillary central incisors: surgical exposure and
      orthodontic treatment: a case report.
AB  - Maxillary central incisor impactions occur infrequently. Their origins include
      various local causes, such as odontoma, supernumerary teeth, and space loss.
      Supernumerary and ectopically impacted teeth are asymptomatic and found during
      routine clinical or radiological examinations. The surgical exposure and
      orthodontic traction of bilaterally impacted central incisors after removal of
      impacted supernumerary teeth is presented in this report.

PMID- 16957797
TI  - AAOMP case challenge: a solitary gingival nodule.
AB  - A 38-year-old Hispanic female presented for evaluation of a gingival nodule of
      eight months duration. The nodule, which was slightly painful to palpation, had
      increased in size over time. The patient denied any history of trauma to the
      area.

PMID- 16957798
TI  - Treating the right patient at the right time: access to specialist consultation
      and non-invasive testing.
AB  - The Council of the Canadian Cardiovascular Society commissioned working groups to
      examine issues of access to, and wait times for, various aspects of
      cardiovascular care. The present article summarizes the deliberations on targets
      for medically acceptable wait times for access to cardiovascular specialist
      evaluation and on the performance of noninvasive testing needed to complete this
      evaluation. Three categories of referral indications were identified: those
      requiring hospitalization due to substantial ongoing risk of mortality and
      morbidity; those requiring an expedited early review in an ambulatory setting;
      and, finally, a larger category in which delays of two to six weeks can be
      justified. The proposed wait time targets will provide guidance on the timeliness
      of care to busy clinicians charged with the care of patients with cardiovascular
      disease, help policy makers appreciate the clinical challenges in providing
      access to high quality care, and highlight the critical need for a thoughtful
      review of cardiology human resource requirements. Wait time implementation
      suggestions are also included, such as the innovative use of disease management
      and special need clinics. The times proposed assume that available clinical
      practice guidelines are followed for clinical coronary syndrome management and
      for treatment of associated conditions such as hypertension, diabetes, renal
      disease, smoking cessation and lipid disorders. Although media attention tends to
      focus on wait times for higher profile surgical procedures and high technology
      imaging, it is likely that patients face the greatest wait-related risk at the
      earlier phases of care, before the disease has been adequately characterized.

PMID- 16957799
TI  - Treating the right patient at the right time: access to cardiovascular nuclear
      imaging.
AB  - Cardiovascular nuclear medicine uses agents labelled with radioisotopes that can
      be imaged with cameras (single-photon emission tomography [SPECT] or positron
      emission tomography [PET]) capable of detecting gamma photons to show
      physiological parameters such as myocardial perfusion, myocardial viability or
      ventricular function. There is a growing body of literature providing guidelines
      for the appropriate use of these techniques, but there are little data regarding
      the appropriate timeframe during which the procedures should be accessed. An
      expert working group composed of cardiologists and nuclear medicine specialists
      conducted an Internet search to identify current wait times and recommendations
      for wait times for a number of cardiac diagnostic tools and procedures, including
      cardiac catheterization and angioplasty, bypass grafting and vascular surgery.
      These data were used to estimate appropriate wait times for cardiovascular
      nuclear medicine procedures. The estimated times were compared with current wait
      times in each province. Wait time benchmarks were developed for the following:
      myocardial perfusion with either exercise or pharmacological stress and SPECT or
      PET imaging; myocardial viability assessment with either fluorodeoxyglucose SPECT
      or PET imaging, or thallium-201 SPECT imaging; and radionuclide angiography.
      Emergent, urgent and nonurgent indications were defined for each clinical
      examination. In each case, appropriate wait time benchmarks were defined as
      within 24 h for emergent indications, within three days for urgent indications
      and within 14 days for nonurgent indications. Substantial variability was noted
      from province to province with respect to access for these procedures. For
      myocardial perfusion imaging, mean emergent/urgent wait times varied from four to
      24 days, and mean nonurgent wait times varied from 15 to 158 days. Only Ontario
      provided limited access to viability assessment, with fluorodeoxyglucose
      available in one centre. Mean emergent/urgent wait times for access to viability
      assessment with thallium-201 SPECT imaging varied from three to eight days, with
      the exception of Newfoundland, where an emergent/urgent assessment was not
      available; mean nonurgent wait times varied from seven to 85 days. Finally, for
      radionuclide angiography, mean emergent/urgent wait times varied from two to 20
      days, and nonurgent wait times varied from eight to 36 days. Again, Newfoundland
      centres were unable to provide emergent/urgent access. The publication of these
      data and proposed wait times as national targets is a step toward the validation
      of these recommendations through consultation with clinicians caring for cardiac
      patients across Canada.

PMID- 16957800
TI  - Lower is better: implications of the Treating to New Targets (TNT) study for
      Canadian patients.
AB  - Recent clinical trials have indicated that lowering low-density lipoprotein
      cholesterol (LDL-C) levels below currently recommended targets results in
      favourable surrogate and clinical end points. The Treating to New Targets (TNT)
      study now confirms that aggressive cholesterol lowering to a mean LDL-C of 2.0
      mmol/L with atorvastatin 80 mg daily, compared with the previous target of 2.5
      mmol/L with atorvastatin 10 mg daily, results in improved clinical outcomes in
      high-risk patients with coronary artery disease. A lower LDL-C target of less
      than 2.0 mmol/L will present therapeutic challenges, because approximately only
      one-half of high-risk patients will achieve this target using monotherapy with
      the newer and more powerful statins. Furthermore, registry data show that one
      half of these patients are not even achieving the current LDL-C target of 2.5
      mmol/L. Causes of the care gap are discussed and possible remedies to achieve the
      new lower targets are suggested.

PMID- 16957801
TI  - Use of cardiovascular medical therapy among patients undergoing coronary artery
      bypass graft surgery: results from the ROSETTA-CABG registry.
AB  - INTRODUCTION: Secondary prevention is needed following coronary artery bypass
      graft (CABG) surgery to reduce the subsequent risk of unstable angina, myocardial
      infarction and death. However, little research exists on the use of
      cardiovascular medical therapy in CABG surgery patients. The objective of the
      present study is to describe the use of cardiovascular medical therapy among
      patients discharged after CABG surgery. METHODS: The use of acetylsalicylic acid,
      clopidogrel, warfarin, antilipid agents, beta-blockers, calcium channel blockers,
      nitrates and angiotensin-converting enzyme (ACE) inhibitors was examined among
      320 patients enrolled in the Routine versus Selective Exercise Treadmill Testing
      After Coronary Artery Bypass Graft Surgery (ROSETTA-CABG) Registry. Logistic
      regression identified the determinants of medication use at 12 months following
      CABG surgery. RESULTS: Most patients were male, hyperlipidemic and underwent CABG
      surgery for relief of angina symptoms. At admission, discharge and at 12 months,
      acetylsalicylic acid was used in 71%, 92% and 87% of cases, respectively, and
      some form of antiplatelet agent was used in 74%, 94% and 89% of cases,
      respectively. The use of antilipid agents remained constant, from 55% at
      admission to 57% at discharge. However, 24% of patients were not receiving
      antilipid agents at 12 months. The use of beta-blockers was 57% at admission, 71%
      at discharge and 64% at 12 months. The use of calcium channel blockers and
      nitrates decreased modestly from admission to discharge and remained stable at
      approximately 20% and 22%, respectively, at 12 months. ACE inhibitor use remained
      stable, from 33% at admission to 38% at 12-months. Hyperlipidemia, hypertension,
      obesity and pre-CABG surgery left ventricular ejection fraction less than 40%
      were all found to be important determinants of 12-month medication use.
      Importantly, the use at discharge was an important determinant of 12-month use of
      for each medication examined in the present study. CONCLUSIONS: The use of
      antilipid agents, beta-blockers and ACE inhibitors was found to be too low among
      post-CABG surgery patients, who are known to benefit from their use, and the use
      of nitrates was too high. Discharge from hospital provides a unique opportunity
      for physicians to modify the use of cardiovascular medical therapy among patients
      undergoing CABG surgery.

PMID- 16957802
TI  - Early outcomes of coronary artery bypass with and without cardiopulmonary bypass
      in octogenarians.
AB  - BACKGROUND: Off-pump coronary artery bypass (OPCAB) surgery has been successfully
      used in diverse patient populations and has been postulated to be safer than
      conventional coronary artery bypass (CCAB) surgery in some high-risk patients,
      including the elderly. OBJECTIVE: To compare the safety of OPCAB surgery versus
      CCAB surgery in the octogenarian population of two large southwestern Ontario
      cardiac surgical units. RESULTS: Two hundred thirty-six consecutive octogenarians
      underwent primary isolated coronary artery bypass surgery from November 2000 to
      March 2005. Patients undergoing OPCAB surgery tended to have higher Parsonnet
      scores, while patients undergoing CCAB surgery had a greater number of emergent
      operations. The Canadian Cardiovascular Network predicted that mortality risk was
      similar in both groups. In-hospital mortality was similar between groups, as was
      postoperative myocardial infarction and new onset of renal dysfunction. However,
      in the OPCAB group, there was a decreased incidence of postoperative neurological
      dysfunction (2.3% in the OPCAB group versus 10.5% in the CCAB group, P=0.01), in
      particular cerebrovascular accidents (1.5% in the OPCAB group versus 7.6% in the
      CCAB group, P=0.05), and a decreased incidence of prolonged intubation (5.3% in
      the OPCAB group versus 13.3% in the CCAB group, P=0.04). Multivariable analysis
      found that cardiopulmonary bypass had no significant impact on mortality or
      length of stay. CONCLUSIONS: In octogenarian patients, OPCAB surgery is as safe
      as CCAB surgery in terms of mortality and major morbidity. Furthermore, a
      significant reduction in neurological dysfunction and prolonged intubation was
      seen in the OPCAB group compared with the CCAB group.

PMID- 16957803
TI  - Treatment and blood pressure control in 47,964 people with diabetes and
      hypertension: a systematic review of observational studies.
AB  - BACKGROUND: Many patients with diabetes also have hypertension, greatly
      increasing their risk for cardiovascular disease. It has been suggested that
      hypertension is poorly treated in those with diabetes. OBJECTIVE: To examine
      treatment and control of hypertension in people with diabetes. DATA SOURCES: Data
      sources included MEDLINE, EMBASE, HealthSTAR, CINAHL, Web of Science, clinical
      evidence and government health and statistical Web sites. METHOD: Databases were
      systematically reviewed and hand searches of the bibliographies of relevant
      studies (1990 to 2004) were conducted. Two investigators selected studies and
      extracted the data independently. RESULTS: A total of 44 studies (77,649 subjects
      with diabetes, 47,964 [62%] of whom also had hypertension) were included. While
      83% (range 32% to 100%) of patients with hypertension received drug therapy, only
      12% (range 6% to 30%) had their blood pressure (BP) controlled to 130/85 mmHg or
      less. While BP control rates differed by definition of control (those studies
      with the least stringent definitions for BP control--160/90 mmHg or less-
      reported mean control rates of 37%), treatment and control rates did not differ
      appreciably between countries or health care settings. CONCLUSIONS: Fewer than
      one in eight people with diabetes and hypertension have adequately controlled BP,
      with remarkable uniformity across studies conducted in a variety of settings.
      There is an urgent need for multidisciplinary, community-based approaches to
      manage these high-risk patients.

PMID- 16957804
TI  - Combination of statin and ezetimibe for the treatment of dyslipidemias and the
      prevention of coronary artery disease.
AB  - The prevention of coronary artery disease (CAD) involves therapeutic lifestyle
      changes such as smoking cessation, diet, weight reduction and exercise. In
      patients with established CAD or atherosclerosis in other vascular beds, or in
      patients at high risk of developing CAD, lowering serum total and low-density
      lipoprotein cholesterol (LDL-C) has been associated with a reduction in
      cardiovascular morbidity and mortality, and total mortality. Recently, large
      scale studies have shown that lowering the LDL-C to less than 2.0 mmol/L is
      associated with a reduction of major cardiac events in patients with established
      CAD. Therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
      (statins) has had a major impact on preventive cardiology. Not all patients reach
      recommended LDL-C targets on currently available statins. Ezetimibe is a
      selective inhibitor of intestinal cholesterol absorption that results in an
      additional 15% to 25% reduction of LDL-C. The recommended dosage is 10 mg once
      daily; it is safe and well tolerated. Elevations in transaminase and creatine
      kinase occur in approximately 1% of subjects. Ezetimibe is suggested for patients
      who do not reach recommended LDL-C targets on an optimal dosage of statins alone.
      While the effects of ezetimibe on atherosclerosis have not been ascertained,
      clinical trials have consistently shown that the reduction in serum cholesterol
      correlates with a decrease in major cardiovascular events, irrespective of the
      method used to reduce cholesterol.

PMID- 16957805
TI  - Myocardial dysfunction in polymyositis.
AB  - Myocardial involvement in polymyositis is occasionally suspected, but symptomatic
      cardiac dysfunction is rarely reported. Described in the present report is a 48
      year-old woman with a two-year history of polymyositis who suddenly developed
      near fatal ventricular arrhythmia, and a 56-year-old man with a relapsing
      polymyositis who developed severe systolic dysfunction. These two cases emphasize
      the importance of systematic cardiac evaluation when the diagnosis of
      polymyositis is initially made and the necessity of re-evaluating cardiac
      function, even in the presence of clinical remission and normalization of
      creatine phosphokinase with treatment.

PMID- 16957807
TI  - Photodegradation of retinol and anti-aging effectiveness of two commercial
      emulsions.
AB  - Two commercial anti-aging products, RETI C and RETI C concentrate emulsions,
      containing retinol and vitamin C, were studied. The concentration of vitamin A
      was determined over time, subjecting the creams to an accelerated stability test.
      Both emulsions, when stored at 25 degrees C, showed a moderate decrease over time
      in retinol concentration, while after storage at 40 degrees C the percentage of
      retinol degraded increased over time. Under UVA irradiation, the retinol degraded
      to a greater extent than under UVB irradiation, both in RETI C and RETI C
      concentrate emulsions. In order to verify the anti-aging effectiveness of the
      emulsions, an in vivo test on some female volunteers was carried out, evaluating
      the visible results of the application of the creams on the skin surface. The
      creams were rather unstable after storage at 40 degrees C, but they were
      effective in treating the signs of aging and in reducing facial wrinkles.

PMID- 16957809
TI  - Comparative efficacy and safety of deoxyarbutin, a new tyrosinase-inhibiting
      agent.
AB  - Several tyrosinase inhibitors have been developed and utilized to ameliorate
      various cutaneous hyperpigmentary disorders and complexion discolorations.
      Deoxyarbutin (dA) (i.e., 4-[(tetrahydro-2H-pyran-2-yl)oxy]phenol), designed using
      quantitative structure-activity relationships (QSAR), demonstrates effective
      inhibition of mushroom tyrosinase and skin-lightening capability (1). However,
      its comparative safety, effectiveness, and reversibility to other known
      tyrosinase inhibitors in human melanocytes had not been determined. The effect of
      dA was assessed in cultured human skin cells, on xenographs, and with a clinical
      trial. Using cultured human melanocytes, the maximum concentration of dA that
      allowed 95% viability was fourfold greater than for hydroquinone (HQ), indicating
      that dA is less cytotoxic/cytostatic than HQ. The viability of cultured human
      keratinocytes and fibroblasts was also less compromised by increasing
      concentrations of dA as opposed to HQ. At the maximum concentration allowing
      normal cellular viability, dA effectively inhibited tyrosinase activity and
      melanin content in human melanocytes, whereas HQ was marginally inhibitory. Upon
      removal of dA, tyrosinase activity and melanin content was normalized within five
      days. Topical application of dA on human xenografts resulted in a gradual and
      visually apparent skin lightening effect during an eight-week period. In a
      clinical trial, dA facilitated fading of pre-tanned skin to a statistically
      significant greater extent than either HQ or no treatment. These results
      demonstrate that dA is a potentially safe, effective, and reversible tyrosinase
      inhibitor.

PMID- 16957808
TI  - Inhibitory effects of antioxidant constituents from Melothria heterophylla on
      matrix metalloproteinase-1 expression in UVA-irradiated human dermal fibroblasts.
AB  - Matrix metalloproteinases (MMPs) are known to play an important role in
      photoaging by mediating the degradation of extracellular matrix proteins. To
      develop a new anti-aging agent for cosmetics from natural products, Melothria
      heterophylla (Lour.) Cogn. was selected for its antioxidant activity and
      inhibitory effect on expression of MMP-1 in UVA-irradiated human skin
      fibroblasts. Two compounds (compounds 1 and 2 ) were isolated from an ethyl
      acetate soluble fraction of the ethanolic extracts; they were identified as
      1,2,4,6-tetra-O-galloyl-beta-(D)-glucopyranose (1) and 3,4,5-trihydroxybenzoic
      acid (2). These compounds were found to scavenge radicals and reactive oxygen
      species (ROS) and were measured to have SC50 values of 3.9 microM and 13.3 microM
      against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and values of 4.3 microM
      and 4.0 microM against superoxide radicals in the xanthine/xanthine oxidase
      system, respectively. Compounds 1 and 2 showed a dose-dependent inhibitory effect
      on the expression and activity of MMP-1 in UVA-induced human skin fibroblasts,
      but no inhibition of MMP-1 mRNA expression. Therefore, we concluded that
      compounds 1 and 2 significantly inhibited MMP-1 expression at the protein level.
      Also, these compounds were determined to have a potent antioxidant activity. From
      these results, we suggest that these compounds might be useful as a new anti
      aging agent for photodamaged skin, but the in vitro findings must be verified in
      in vivo studies.

PMID- 16957811
TI  - Morphology and properties of Asian and Caucasian hair.
AB  - Various aspects of Asian and Caucasian hairs were investigated and compared. We
      started by studying their cuticle structures--the number of cuticle layers, width
      of the cuticle cells, degree of their inclination, and the interval between
      surface cuticle edges. As a result of this study, on about two hundred subjects
      for each race, it was shown that there were statistically meaningful differences
      between all these attributes for the two hair types. Asian hair has more cuticle
      layers and wider cuticle cells than Caucasian hair, and the cuticular inclination
      of Asian hair is steeper and its cuticular interval is narrower than in Caucasian
      hair. In addition, it was also found that there are differences in how cuticle
      cells begin to fail. Under extension stress, Asian hair cuticles fail as large
      pieces while keeping their original shape. On the other hand, Caucasian hair
      cuticles tend to collapse to form small fragments. AFM measurements revealed that
      Caucasian cuticles are indeed more fragile than Asian cuticles. These results
      suggest that the strength of cuticular subcomponents is different between Asian
      and Caucasian hair and that the weakest point, where stress is first absorbed,
      differs between races. It was proven that the cuticles of Asian hair are more
      easily peeled off than Caucasian hair cuticles during daily grooming. This can be
      attributed to the difference in how stress is absorbed.

PMID- 16957810
TI  - Microemulsions of triglyceride-based oils: The effect of co-oil and salinity on
      phase diagrams.
AB  - Microemulsification of triglyceride-based oil is challenging due to the formation
      of undesirable phases such as macroemulsions, liquid crystals, or sponge phases.
      This research evaluates the formation of artificial sebum microemulsions using
      linker molecules, with the addition of co-oil to help enhance sebum
      solubilization. The microemulsion consists of a lipophilic linker (sorbitan
      monooleate), a hydrophilic linker (hexylglucocide), a main surfactant (sodium
      dioctyl sulfosuccinate), a co-oil, and artificial sebum. The effect of adding co
      oil to the phase behavior and the microstructure of the resulting microemulsion
      is described. The effect of several types of co-oil is also studied; the co-oils
      evaluated here are squalene, squalane, isopropyl myristate, and ethyl laurate.
      The effect of salinity on the microemulsion phase behavior is also presented.
      Fish diagrams are obtained by plotting total surfactant/linker concentration as a
      function of sebum fraction in the oil mixture (co-oil + sebum). Different
      microemulsion types (Winsor Types I, II, III, and IV) are formed, depending on
      the total surfactant/linker concentration and the fraction of co-oil in the oil
      mixture. Winsor Type IV (single-phase) microemulsions are observed at high
      surfactant/linker concentrations. These single-phase, isotropic, and low-viscous
      fluids are particularly useful for cleansing and delivery of functional
      ingredients in skin care products. Salt addition shifts the fish diagram towards
      more hydrophobic oil systems and higher surfactant/linker concentrations.

PMID- 16957813
TI  - Similarity of the allele frequency and linkage disequilibrium pattern of single
      nucleotide polymorphisms in drug-related gene loci between Thai and northern East
      Asian populations: implications for tagging SNP selection in Thais.
AB  - The similarity of the marker allele frequency and linkage disequilibrium
      structure between two populations are major factors for the determination of the
      transferability and efficiency of haplotype tagging SNP derived from one
      population to use for an indirect association study in another population. To
      prove the similarity between northern East Asian populations in Hapmap and Thais,
      861 SNP in 166 drug-related genes shared between Thais, Han Chinese and Japanese
      were analyzed for their correlation statistics. Allele frequency, Fst statistics
      and linkage disequilibrium statistics (r (2)) showed a high correlation between
      these populations. TagSNP sets derived by an aggressive tagging algorithm from
      these 861 SNP in Japanese and Chinese were used to test the coverage of East Asia
      derived tagSNP in Thais. TagSNP derived from Japanese and Chinese are comparable
      in the percentage of coverage of the alleles captured with tagSNP at r (2)>or=0.8
      (93% vs. 93%) in these drug-related gene loci. Additional tagSNP sets derived
      from the combination of Japanese- and Chinese-derived tagging SNP sets were used
      to test the coverage in Thais. The later set improved the percentage of coverage
      of alleles captured with tagSNP at r (2)>or=0.8-98% for these sites. High
      similarity between Thais and northern East Asian allele frequency and linkage
      disequilibrium statistics supported that tagSNPs derived from the northern East
      Asian population should be useful for an indirect association study in Thais. The
      combination of non-overlapping Japanese derived tagSNP and Chinese-derived tagSNP
      improved the percentage of genomic coverage in Thais, at least in these drug
      related gene loci.

PMID- 16957814
TI  - A prospective study of dietary patterns, meat intake and the risk of gestational
      diabetes mellitus.
AB  - AIMS/HYPOTHESIS: The aim of this study was to prospectively examine whether
      dietary patterns are related to risk of gestational diabetes mellitus (GDM).
      METHODS: This prospective cohort study included 13,110 women who were free of
      cardiovascular disease, cancer, type 2 diabetes and history of GDM. Subjects
      completed a validated semi-quantitative food frequency questionnaire in 1991, and
      reported at least one singleton pregnancy between 1992 and 1998 in the Nurses'
      Health Study II. Two major dietary patterns (i.e. 'prudent' and 'Western') were
      identified through factor analysis. The prudent pattern was characterised by a
      high intake of fruit, green leafy vegetables, poultry and fish, whereas the
      Western pattern was characterised by high intake of red meat, processed meat,
      refined grain products, sweets, French fries and pizza. RESULTS: We documented
      758 incident cases of GDM. After adjustment for age, parity, pre-pregnancy BMI
      and other covariates, the relative risk (RR) of GDM, comparing the highest with
      the lowest quintile of the Western pattern scores, was 1.63 (95% CI 1.20-2.21; p
      (trend)=0.001), whereas the RR comparing the lowest with the highest quintile of
      the prudent pattern scores was 1.39 (95% CI 1.08-1.80; p (trend)=0.018). The RR
      for each increment of one serving/day was 1.61 (95% CI 1.25-2.07) for red meat
      and 1.64 (95% CI 1.13-2.38) for processed meat. CONCLUSIONS/INTERPRETATION: These
      findings suggest that pre-pregnancy dietary patterns may affect women's risk of
      developing GDM. A diet high in red and processed meat was associated with a
      significantly elevated risk.

PMID- 16957815
TI  - Immunolocalization of tight junction proteins in blood vessels in human germinal
      matrix and cortex.
AB  - Brain development occurs in a specialized environment maintained by a blood-brain
      barrier (BBB). An important structural element of the BBB is the endothelial
      tight junction (TJ). TJs are present during the embryonic period, but BBB
      impermeability accrues over an extended gestational interval. In studies of human
      premature infants, we used immunomicroscopy to determine if amounts of the TJ
      proteins ZO-1, claudin and occludin increase with gestational age in vessels of
      germinal matrix (GM) and cortex. By 24 weeks postconception (PC), TJ proteins
      were present in both GM and cortical vessels, but immunoreactivity in the GM of
      the youngest subjects was less than in older subjects. At 24 weeks PC, TJ protein
      immunoreactivity in GM vessels was less than in cortical vessels suggesting that
      TJ maturation progresses along a superficial to deep brain axis. This concept
      correlates with conclusions from previous analyses of the expression of brain
      endothelial cell alkaline phosphatase (AP) activity. AP appears in cortical
      vessels before appearing in deep white matter and GM vessels. Together, these
      data indicate that differentiation of some functional specializations is still in
      progress in GM vessels during the third trimester. This maturation could relate
      to the pathogenesis of germinal matrix hemorrhage-intraventricular hemorrhage.

PMID- 16957816
TI  - Nuclear myosin is ubiquitously expressed and evolutionary conserved in
      vertebrates.
AB  - Nuclear myosin I (NMI) is a single-headed member of myosin superfamily localized
      in the cell nucleus which participates along with nuclear actin in transcription
      and chromatin remodeling. We demonstrate that NMI is present in cell nuclei of
      all mouse tissues examined except for cells in terminal stages of spermiogenesis.
      Quantitative PCR and western blots demonstrate that the expression of NMI in
      tissues varies with the highest levels in the lungs. The expression of NMI is
      lower in serum-starved cells and it increases after serum stimulation. The
      lifespan of NMI is longer than 16 h as determined by cycloheximide translation
      block. A homologous protein is expressed in human, chicken, Xenopus, and
      zebrafish as shown by RACE analysis. The analysis of genomic sequences indicates
      that almost identical homologous NMI genes are expressed in mammals, and similar
      NMI genes in vertebrates.

PMID- 16957817
TI  - Is the quality of life better in patients with colostomy than patients with fecal
      incontience?
AB  - BACKGROUND: A colostomy offers definitive treatment for individuals with fecal
      incontinence (FI). Patients and physicians remain apprehensive regarding this
      option because the quality of life (QOL) with a colostomy is presumably worse
      than living with FI. The aim of this study, therefore, was to compare the QOL of
      colostomy patients to patients with FI. METHODS: A cross-sectional postal survey
      of patients with FI or an end colostomy was undertaken. QOL measures used
      included the Short Form 36 General Quality of Life Assessment (SF-36) and the
      Fecal Incontinence Quality of Life score (FIQOL). RESULTS: The colostomy group
      included 39 patients and the FI group included 71 patients. The average FI score
      for FI group was 12 +/- 4.9 (0 = complete continence, 20 = severe incontinence).
      In the colostomy group the average colostomy function score was 12.9 +/- 3.8 (7 =
      good function, 35 = poor function). Analysis of the SF-36 revealed higher social
      function score in the colostomy group compared to the FI group. Analysis of the
      FIQOL revealed higher scores in the coping, embarrassment, lifestyle scales, and
      depression scales in the colostomy group compared to the FI group. CONCLUSION: A
      colostomy is a viable option for patients who suffer from FI and offers a
      definitive cure with improved QOL.

PMID- 16957818
TI  - Mortality in terrorist attacks: a unique modal of temporal death distribution.
AB  - BACKGROUND: Terror-related multiple casualty incidents (MCI) in Israel since
      September 2000 have resulted in a new pattern of injury as a result of the
      mechanisms of trauma. The objective of this study was to asses the temporal death
      distribution among the civilian casualties in the Jerusalem vicinity during a 3
      year period. METHODS: All terrorist attacks in the Jerusalem district from
      September 2000 to September 2003 were included in this study. The data of all
      deaths were processed including the time of the attack, the evacuation time to
      the hospitals, and the time of death. RESULTS: During the study period 28 terror
      related MCI occurred. A total of 2328 victims were injured and 273 died, for an
      overall fatality rate of 11.7%. A unique temporal death distribution was
      identified; 82.8% of the deaths occurred immediately, at the scene of the attack
      (scene death); of the remaining 17.2% of patients who died in the hospital, half
      died within 4 hours of arrival (immediate death), one quarter within 5-24 hours
      (early death), and one quarter later than that (late death). The temporal death
      distribution was significantly different when classifying the mechanism of trauma
      to suicide bombings versus shooting. The scene mortality was higher in the
      suicide bombings than in shooting attacks (86.7% versus 77%, P = 0.039 ). In
      contrast, the mortality within 1-24 hours was higher in the shooting attacks (17%
      versus 6.3%, P = 0.05). CONCLUSIONS: Terror-related MCI occurring in civilian
      settings have a unique temporal death distribution. A very high scene mortality
      is seen compared to the classical description of Donald Trunkey1 in 1983. The
      late deaths, which composed 30% of the mortality in civilian settings, comprise
      only 4.4% of the total mortality in MCIs. A rough estimate of the in-hospital
      mortality could be achieved after the first 4 hours, allowing the assessment and
      distribution of hospital resources. Futile care should be identified early and
      availability of ICU beds can be calculated according to the immediate mortality.

PMID- 16957820
TI  - Postoperative anal stenoses with Ligasure hemorrhoidectomy.

PMID- 16957821
TI  - Postoperative complications in obese and nonobese patients.
AB  - BACKGROUND: Postoperative complications are undesirable and potentially common in
      the increasing obese population of surgical patients. There is a scarcity of
      recent and reliable studies comparing postoperative morbidity and mortality in
      obese and nonobese patients. The aim of this study was to evaluate the
      prevalence, pattern, and severity of postoperative complications in obese and
      nonobese surgical patients. METHODS: A retrospective review and analysis of adult
      postoperative complications recorded on an electronic database was conducted. The
      database covered a period of 4 years and consisted of 7,271 cases of
      postoperative complications that occurred within 30 days of noncardiac moderate
      or major surgery. Appropriate data and variables were compared between obese and
      nonobese patients using the SPSS program. RESULTS: The rate of postoperative
      complications was 7.7%. Obese patients had a higher prevalence of myocardial
      infarction (P = 0.001), peripheral nerve injury (P = 0.039), wound infection (P =
      0.001), and urinary tract infection (P = 0.004). ). Morbidly obese patients had a
      higher mortality rate of 2.2% compared with 1.2%; for all other patients (P =
      0.034) and a higher prevalence of tracheal reintubation (P = 0.009) and cardiac
      arrest (P = 0.015). Obese patients had higher American Society of
      Anesthesiologists (ASA) physical status scores than other patients (P = 0.001).
      CONCLUSIONS: Obese patients have a significantly higher risk of postoperative
      myocardial infarction, wound infection, nerve injury, and urinary infection.
      Obesity is an independent risk factor for perioperative morbidity, and morbid
      obesity is a risk factor for mortality.

PMID- 16957822
TI  - A brief overview of acute respiratory distress syndrome.
AB  - BACKGROUND: The low pO: (2) in traumatic and septic shock was first documented at
      Walter Reed Army Medical Center starting in 1960. It was postulated that this
      respiratory failure was due to the occlusion of the pulmonary microcirculation by
      the microclots of disseminated intravascular coagulation (DIC). MATERIALS AND
      METHODS: Animal studies showed that pulmonary failure and death could be caused
      by intravenous injection of a killed culture of either Escherichia coli or
      pneumococcal organisms or by severe muscle contusion. Severe clinical septic and
      traumatic shock cases were studied. RESULTS: Injection of either killed E. coli
      or killed pneumococci resulted in acute respiratory distress syndrome (ARDS) and
      death in pigs. Muscle contusion also resulted in ARDS and death in pigs. Both
      ARDS and death were prevented by administration of a plasminogen activator, and
      ARDS in human septic or traumatic shock were safely and effectively treated by
      administration of a plasminogen activator. CONCLUSIONS: Acute respiratory
      distress syndrome can be caused by DIC, which blocks the microcirculation of any
      and all organs. These microclots can be safely lysed by a plasminogen activator,
      thus treating ARDS and saving lives.

PMID- 16957823
TI  - Necrotizing soft tissue infection of the thigh: consider an abdominal cause.
AB  - BACKGROUND: Necrotizing soft tissue infection (NSTI) is a disastrous infection of
      the subcutaneous tissue and underlying fascial layers. Even if urgent treatment
      is started, mortality rates are high. Due to the paucity of specific cutaneous
      signs, early recognition is extremely difficult. This in turn causes a delay in
      diagnosis and worsens prognosis. Although NSTI can develop after a wide variety
      of causes, specific clues such as initial gram staining and a high index of
      suspicion should alert the clinician to an abdominal causative agent, which
      alters surgical treatment strategy. If detected early, prognosis for the patient
      is improved. METHODS: Four patients with NSTI of the thigh due to an abdominal
      origin are detailed regarding their clinical presentation, gram stain or culture,
      abdominal focus, and treatment. Based on our clinical experience and a review of
      the relevant literature, we address clinical challenges and controversies of
      importance. RESULTS: Current literature on NSTI recommends prompt surgical
      debridement and broad-spectrum antibiotic therapy. Our cases revealed that an
      abdominal focus is not uncommon; however, it can be easily missed, which delays
      treatment. All cases demonstrated polymicrobial gram stains and cultures, which
      can raise suspicion of and lead to determination of an abdominal focus.
      CONCLUSIONS: High clinical suspicion or a polymicrobial gram stain or culture
      should quickly lead to determination of an abdominal source. Early surgical
      exploration and focus treatment, together with prompt surgical debridement and
      broad-spectrum antibiotic therapy, could reduce mortality significantly.

PMID- 16957825
TI  - Prognostic factors in periampullary and pancreatic tumor resection in elderly
      patients.
AB  - BACKGROUND: More than half of all patients with pancreatic adenocarcinoma are
      over 70 years of age. Life expectancy for the elderly population is increasing
      and currently major pancreatic resection provides the only meaningful chance of
      cure for periampullary and pancreatic tumors. Controversy over what constitutes
      the correct treatment of these tumors in elderly patients continues to this day.
      The aim of our study was to determine whether age alone or age plus some
      prognostic factors constitute contraindications to major pancreatic resections.
      METHODS: Between 2000 and 2005, data from 88 consecutive patients who had major
      pancreatic resection for periampullary or pancreatic tumors were entered into a
      prospective database. Fifty-three patients under 70 years of age (young
      patients), and 35 patients 70 years of age or older (elderly patients) were
      compared with respect to several characteristics and the postoperative course.
      RESULTS: Postoperative mortality and morbidity, length of hospital stay, and long
      term survival were similar in the two groups. In the elderly group, the mortality
      rate was significantly higher in patients with chronic obstructive pulmonary
      disease (COPD), and the morbidity rate was significantly higher in patients with
      ASA 3 than in patients with ASA 1-2, in whom a pancreaticoduodenectomy or total
      pancreatectomy had been performed. CONCLUSIONS: Age alone is not a
      contraindication for major pancreatic resection. In elderly patients a careful
      evaluation of the co-morbidities and of the type of surgical procedure is
      mandatory in order to allow the proper selection of those patients best suited
      for surgery in specialized centers.

PMID- 16957827
TI  - Detection and sequence-based typing of human adenoviruses using sensitive
      universal primer sets for the hexon gene.
AB  - The universal primer sets for identification of human adenovirus (HAdV) targeting
      hexon gene were designed and applied to 121 clinical samples suspected of HAdV
      infection. The primer sets amplified at least 20 HAdV reference strains of six
      species. Of these clinical samples, 81 (66.9%) samples were positive for HAdV.
      They were classified into 11 serotypes belonging to 5 HAdV species (B-F). The
      primer sets described here are sensitive and reactive to the broad spectrum of
      HAdV and are useful for rapid diagnosis of various HAdV infections.

PMID- 16957826
TI  - Surgical outcomes for gastric cancer in the upper third of the stomach.
AB  - INTRODUCTION: The proportion of gastric cancers affecting the upper third of the
      stomach has been increasing. At our surgical service we perform total and
      proximal gastrectomy for this condition. The purpose of this study was to
      investigate the surgical outcome of the two operative procedures and determine an
      optimal surgical approach. METHODS: Data from 147 patients who underwent
      resection for gastric cancer affecting the proximal one-third of the stomach were
      retrospectively analyzed. The patients were classified into a total gastrectomy
      (TG) group or a proximal gastrectomy (PG) group, and the clinicopathologic
      characteristics and surgical results were compared. We analyzed survival rates
      using Kaplan-Meier methods and made comparisons using a log-rank test across the
      same stage of the gastric cancer. RESULTS: From 1992 to 2000, a total of 104
      total gastrectomies and 43 proximal gastrectomies for gastric cancer affecting
      the upper one-third of the stomach were performed. Our investigation revealed
      significantly different clinicopathologic characteristics in Borrmann type,
      length of the resection margin, degree of lymph node dissection, and lymph node
      stage. During the procedure, a combined resection of other organs was performed
      in 30 TG and 27 PG patients. Postoperative complications developed in 15 TG and
      22 PG patients. The cancer recurrence rate was 4.8% for the TG group and 39.5%
      for the PG group; it was highest when the length of the proximal resection margin
      was < 1 cm. When we compared 5-year survival rates between the two groups, each
      at the same cancer stage, a significant difference was noted for stage III and IV
      gastric cancers. CONCLUSIONS: Proximal gastrectomy may be performed during the
      early stage of proximal gastric cancer; but because of the high frequency of
      complications and cancer recurrence, an additional procedure should be expected
      afterward. When the cancer stage is advanced, total gastrectomy should be
      performed with sufficient length of the proximal resection margin.

PMID- 16957828
TI  - The variable codons of H3 influenza A virus haemagglutinin genes.
AB  - We have analyzed several sets of well-studied haemagglutinin (HA) gene sequences
      of H3 subtype influenza A viruses to identify codons that are unusually variable,
      using a simple pairwise sliding window method, DnDscanning. For two of the sets
      there were results of detailed phylogenetic modeling studies of selection already
      published. A third set had been the subject of an antigen mapping study, the
      results of which provide a completely independent benchmark of selected changes
      in H3 HA genes. Our analyses show that the codons with greatest DnDscan scores
      (i.e. the most variable) were mostly those reported in the published studies as
      being positively selected; indeed the DnDscan results matched the antigenic
      mapping results more closely than did those of the phylogenetic modeling methods.
      These results suggest that codons under selection can be found even when, as with
      some sets of virus sequences, a phylogeny is uncertain or cannot be obtained
      because, for example, the sequences are recombinants, or when selection is not
      necessarily linked with phylogeny, as in host-switching events. The program
      DnDscan is available at (biojanus.anu.edu.au).

PMID- 16957829
TI  - Molecular-weight dependence of the glass transition temperature of freely
      standing poly(methyl methacrylate) films.
AB  - We have used transmission ellipsometry to measure the glass transition
      temperature, T(g), of freely-standing films of atactic and syndiotactic
      poly(methyl methacrylate) (PMMA). We have prepared films with different molecular
      weights, MW, (159 x 10(3) < M (w) < 1.3 x 10(6)) and film thicknesses, h, ( 30 nm
      < h < 200 nm). For the high-MW ( M (w) > 509 x 10(3)) atactic PMMA films, we find
      that T(g) decreases linearly with decreasing h, which is qualitatively similar to
      previous results obtained for high-MW freely-standing polystyrene (PS) films.
      However, the overall magnitude of the T(g) reduction is much less (by roughly a
      factor of three) for the high-MW freely-standing PMMA films than for freely
      standing PS films of comparable MW and h. The observed differences between the
      freely-standing PMMA and PS film data suggest that differences in chemical
      structure determine the magnitude of the T(g) reduction and we discuss the
      possible origins of these differences. Our analysis of the MW-dependence of the
      T(g) reductions suggests that the mechanism responsible for the MW-dependent T(g)
      reductions observed in the high-MW freely-standing films is different than that
      responsible for the MW-independent T(g) reductions observed in the low-MW freely
      standing and supported films.

PMID- 16957830
TI  - Budding and fission of a multiphase vesicle.
AB  - We present a model of bi-phasic vesicles in the limit of large surface tension.
      In this regime, the vesicle is completely stretched and well described by two
      spherical caps with a fold, which concentrates the membrane stress. The
      conservation laws and geometric constraints restrict the space of possible shapes
      to a pair of solutions labeled by a parameter sigma given by line
      tension/pressure. For a given value of sigma, the two solutions differ by the
      length of the interface between domains. For a critical value, sigmac, the two
      vesicle shapes become identical and no connected solution exists above this
      critical value. This model sheds new light on two proposed mechanisms (osmotic
      shocks and molecule absorption) to explain the budding and the fission in recent
      experiments.

PMID- 16957831
TI  - Size and stability of liposomes: a possible role of hydration and osmotic forces.
AB  - Dynamic light scattering and electrophoretic mobility measurements have been used
      to characterize the size, size distribution and zeta potentials (zeta-potentials)
      of egg yolk phosphatidylcholine (EYPC) liposomes in the presence of monovalent
      ions ( Na(+) and K(+)). To study the stability of liposomes the Derjaguin-Landau
      Verwey-Overbeek (DLVO) theory has been extended by introducing the hydrated
      radius of the adsorbed ions onto the liposome surfaces. The decrease of liposome
      size is explained on the basis of the membrane impermeability to some ions which
      generate osmotic forces, which leads to evacuate water from liposome inside.

PMID- 16957832
TI  - Bubbles and denaturation in DNA.
AB  - The local opening of DNA is an intriguing phenomenon from a statistical-physics
      point of view, but is also essential for its biological function. For instance,
      the transcription and replication of our genetic code cannot take place without
      the unwinding of the DNA double helix. Although these biological processes are
      driven by proteins, there might well be a relation between these biological
      openings and the spontaneous bubble formation due to thermal fluctuations.
      Mesoscopic models, like the Peyrard-Bishop-Dauxois (PBD) model, have fairly
      accurately reproduced some experimental denaturation curves and the sharp phase
      transition in the thermodynamic limit. It is, hence, tempting to see whether
      these models could be used to predict the biological activity of DNA. In a
      previous study, we introduced a method that allows to obtain very accurate
      results on this subject, which showed that some previous claims in this
      direction, based on molecular-dynamics studies, were premature. This could either
      imply that the present PBD model should be improved or that biological activity
      can only be predicted in a more complex framework that involves interactions with
      proteins and super helical stresses. In this article, we give a detailed
      description of the statistical method introduced before. Moreover, for several
      DNA sequences, we give a thorough analysis of the bubble-statistics as a function
      of position and bubble size and the so-called l-denaturation curves that can be
      measured experimentally. These show that some important experimental observations
      are missing in the present model. We discuss how the present model could be
      improved.

PMID- 16957833
TI  - Osteocytes--martyrs for integrity of bone strength.

PMID- 16957834
TI  - Phase II trial of nolatrexed dihydrochloride [Thymitaq, AG 337] in patients with
      advanced hepatocellular carcinoma.
AB  - BACKGROUND: To evaluate the tolerability and efficacy of nolatrexed in patients
      with advanced hepatocellular carcinoma. PATIENTS AND METHODS: Forty-eight
      patients were entered onto this study. Nolatrexed was administered every 3 weeks
      as a 24-h continuous intravenous infusion of 725 mg/m(2)/day for 5 days. Doses
      were adjusted to maintain a dose level that produced > or = grade 2 toxicity.
      Response was assessed after every two cycles. Plasma pharmacokinetic samples were
      assayed using a validated high performance liquid chromatography ultraviolet
      method. RESULTS: Thirty-nine (81%) patients were evaluable for response. The mean
      number of cycles received was 2.8 (range 1-12). The mean dose intensity was 700
      mg/m(2)/day (SD of 71). One patient had a partial response (2.6%) for 7 months.
      Eighteen (46%) patients had SD, 20 (51%) patients had progressive disease. The
      median duration of SD was 93 days. The median overall survival was 32 weeks [95%
      CI (22-37)]. The most frequent Grade 3 or 4 adverse events were stomatitis (25%),
      dehydration (23%) and asthenia (21%). There was no evidence of cumulative
      toxicity. The overall median plasma concentration (C (max)) was 14.20 microg/mL
      (range 1.41 to 119 microg /mL) with no accumulation observed between cycles 1-6.
      CONCLUSION: This phase II study of nolatrexed in advanced HCC patients,
      demonstrated minimal activity and significant stomatitis. Hence, it does not
      warrant further study as a single agent for this disease.

PMID- 16957836
TI  - George Zografi: researcher and educator.

PMID- 16957835
TI  - A phase II, open label, monotherapy study of liposomal doxorubicin in patients
      with metastatic malignant melanoma.
AB  - PURPOSE: This phase II study explored the efficacy and tolerability of pegylated
      liposomal doxorubicin (PLD) given on a 2 week schedule in patients with advanced
      malignant melanoma previously untreated by chemotherapy. PATIENTS AND METHODS:
      Patients with inoperable, advanced melanoma were treated with Pegylated liposomal
      doxorubicin (Caelyx) at a dose of 20 mg/m(2) every 2 weeks. Treatment cycles were
      repeated every 4 weeks for a maximum of 6 cycles. Patients with responding or
      stable disease at the end of study treatment, as assessed by using NCI CTG
      criteria, could continue PLD off-study. RESULTS: PLD administered as a 2 weekly
      IV infusion was well tolerated with mild infusion reactions usually associated
      with the first infusion. Myelosuppression was mild, as was nausea and vomiting.
      Palmar plantar erythrodysesthesia was also uncommon using this schedule. There
      were no objective responses seen in the 14 evaluable patients. Enrollment was
      stopped as per protocol, due to lack of activity. CONCLUSION: PLD was well
      tolerated using a 2 week schedule but failed to show any activity in chemotherapy
      naive patients with advanced malignant melanoma.

PMID- 16957837
TI  - Facile and sensitive spectrophotometric determination of carbosulfan in
      formulations and environmental samples.
AB  - Facile, selective and sensitive spectrophotometric method has been developed for
      the determination of carbosulfan in insecticidal formulations, fortified water,
      food grains, agriculture wastewater and soil samples with newly synthesized
      reagents. The method was based on acid and alkaline hydrolysis of the carbosulfan
      pesticide, and the resultant hydrolysis product of carbosulfan was coupled with
      2,6-dibromo-4-methylaniline to give a yellow color product with lambda(max) of
      464 nm or interaction with 2,6-dibromo-4-nitroaniline to produce yellow colored
      product with lambda(max) of 408 nm or coupling with 2,4,6-tribromoaniline to form
      red colored product has a lambda(max) of 471 nm. Under optimal conditions, Beer's
      law range for 2,6-dibromo-4-methylaniline (DBMA) was found to be 0.2-12.0 microg
      ml(-1), 0.6-16.0 microg ml(-1) for 2,6-dibromo-4-nitroaniline (DBNA) and 0.4-15.0
      microg ml(-1) for 2,4,6-tribromoaniline (TBA). The molar absorptivity of the
      color systems were found to be 3.112 x 10(4) l mol(-1) cm(-1) for DBMA, 3.214 x
      10(4) l mol(-1) cm(-1) for DBNA and 3.881 x 10(4) l mol(-1) cm(-1) for TBA.
      Sandell's of the color reactions are 0.013 microg cm(-2) (DBMA), 0.012 microg cm(
      2) (DBNA) and 0.011 microg cm(-2) (TBA) respectively. The effect of the non
      target species on the determination of carbosulfan was studied to enhance the
      selectivity of the proposed methods. The formation of colored derivatives with
      the coupling agents is instantaneous and stable for 28, 30, and 26 h. Performance
      of the proposed methods were compared statistically in terms Student's F and t
      tests with the reported methods.

PMID- 16957838
TI  - Impact assessment and recommendation of alternative conjunctive water use
      strategies for salt affected agricultural lands through a field scale decision
      support system - a case study.
AB  - Conjunctive use of saline/non-saline irrigation waters is generally aimed at
      minimizing yield losses and enhancing flexibility of cropping, without much
      alteration in farming operations. Recommendation of location-specific suitable
      conjunctive water use plans requires assessment of their long-term impacts on
      soil salinization/sodification and crop yield reductions. This is conventionally
      achieved through long-term field experiments. However such impact evaluations are
      site specific, expensive and time consuming. Appropriate decision support systems
      (DSS) can be time-efficient and cost-effective means for such long-term impact
      evaluations. This study demonstrates the application of one such (indigenously
      developed) DSS for recommending best conjunctive water use plans for a, rice
      wheat growing, salt affected farmer's field in Gurgaon district of Haryana
      (India). Before application, the DSS was extensively validated on several farmers
      and controlled experimental fields in Gurgaon and Karnal districts of Haryana
      (India). Validation of DSS showed its potential to give realistic estimates of
      root zone soil salinity (with R = 0.76-0.94; AMRE = 0.03-0.06; RMSPD = 0.51
      0.90); sodicity (with R = 0.99; AMRE = 0.02; RMSPD = 0.84) and relative crop
      yield reductions (AMRE = 0.24), under existing (local) resource management
      practices. Long term (10 years) root zone salt build ups and associated
      rice/wheat crop yield reductions, in a salt affected farmer's field, under varied
      conjunctive water use scenarios were evaluated with the validated DSS. It was
      observed that long-term applications of canal (CW) and tube well (TW) waters in a
      cycle and in 1:1 mixed mode, during Kharif season, predicted higher average root
      zone salt reductions (2-9%) and lower rice crop yield reductions (4-5%) than the
      existing practice of 3-CW, 3-TW, 3-CW. Besides this, long-term application of 75%
      CW mixed with 25% TW, during Rabi season, predicted about 17% lower average root
      zone salt reductions than the cyclic applications of (1-CW, 1-TW, 2-CW) and (2
      CW, 1-TW, 1-CW, i.e., existing irrigation strategy). However, average wheat crop
      yield reductions (16-17%) simulated under all these strategies were almost at
      par. In general, cyclic-conjunctive water use strategies emerged as better
      options than the blending modes. These results were in complete confirmation with
      actual long-term conjunctive water use experiments on similar soils. It was thus
      observed that such pre-validated tools could be efficient means for designing,
      local resource and target crop yield-specific, appropriate conjunctive water use
      plans for irrigated agricultural lands.

PMID- 16957839
TI  - Biomonitoring of lead, zinc, and cadmium in streams draining lead-mining and non
      mining areas, southeast Missouri, USA.
AB  - We evaluated exposure of aquatic biota to lead (Pb), zinc (Zn), and cadmium (Cd)
      in streams draining a Pb-mining district in southeast Missouri. Samples of plant
      biomass (detritus, periphyton, and filamentous algae), invertebrates (snails,
      crayfish, and riffle benthos), and two taxa of fish were collected from seven
      sites closest to mining areas (mining sites), four sites further downstream from
      mining (downstream sites), and eight reference sites in fall 2001. Samples of
      plant biomass from mining sites had highest metal concentrations, with means 10-
      to 60-times greater than those for reference sites. Mean metal concentrations in
      over 90% of samples of plant biomass from mining sites were significantly greater
      than those from reference sites. Mean concentrations of Pb, Zn, and Cd in most
      invertebrate samples from mining sites, and mean Pb concentrations in most fish
      samples from mining sites, were also significantly greater than those from
      reference sites. Concentrations of all three metals were lower in samples from
      downstream sites, but several samples of plant biomass from downstream sites had
      metal concentrations significantly greater than those from reference sites.
      Analysis of supplemental samples collected in the fall of 2002, a year of above
      average stream discharge, had lower Pb concentrations and higher Cd
      concentrations than samples collected in 2001, near the end of a multi-year
      drought. Concentrations of Pb measured in fish and invertebrates collected from
      mining sites during 2001 and 2002 were similar to those measured at nearby sites
      in the 1970s, during the early years of mining in the Viburnum Trend. Results of
      this study demonstrate that long-term Pb mining activity in southeast Missouri
      has resulted in significantly elevated concentrations of Pb, Cd, and Zn in biota
      of receiving streams, compared to biota of similar streams without direct
      influence of mining. Our results also demonstrate that metal exposure in the
      study area differed significantly among sample types, habitats, and years, and
      that these factors should be carefully considered in the design of biomonitoring
      studies.

PMID- 16957841
TI  - The influence of dioxide chloride on water quality of Balneario Camboriu beach,
      Brazil.
AB  - Since February 1999, the Municipal Wastewater Treatment Plant (MWTP) of Balneario
      Camboriu, Brazil, started a complementary treatment with ClO(2) application on
      its effluent. It was realized to minimize its impacts caused by increase of the
      population during summer. This study was realized in order to verify the
      influence of this compound in the water quality and the environmental
      evaluations. Samples of surface water were collected in this environment between
      January 1997 and June 2001 for chemical and microbiological surveys. The results
      had shown that after application of ClO(2), fecal coliforms were decreased about
      six times in the beach (2.3 x 10(3) to 3.5 x 10(2) MPN/100 ml) and three times in
      the river (3.3 x 10(4) to 1.0 x 10(4) MPN/100 ml), during summer time. NH(4) (+)
      showed an increase of about four times and 1.5 times, respectively, to beach and
      river. These results are showing the influence of ClO(2) on chemical and
      microbiological parameters.

PMID- 16957840
TI  - Assessment of atmospheric deposition of heavy metals and other elements in
      Belgrade using the moss biomonitoring technique and neutron activation analysis.
AB  - This study aimed at assessing atmospheric deposition of heavy metals and other
      elements using the moss genera Brachythecium sp. (B. rutabulum and B. salebrosum)
      and Eurhynchium sp. (E. hians and E. striatum) collected in autumn 2004 in the
      urban area of Belgrade. The concentrations of 36 elements (Na, Mg, Al, Cl, K, Ca,
      Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Zn, As, Se, Br, Rb, Sr, Mo, Sb, I, Cs, Ba, La, Ce,
      Sm, Tb, Dy, Hf, Ta, W, Hg, Th, U) were determined in moss and local topsoil
      samples by instrumental neutron activation analysis. The concentration of
      elements in moss positively correlated to those obtained for topsoil. High
      enrichment factors for As, Zn, Mo, Br, Sb, Se, Hg and Cl, calculated to
      continental crust composition, gave an evidence for anthropogenic impact on urban
      area, mainly due to intensive vehicular traffic and fossil fuel combustion. The
      concentration of elements in moss, characteristic for fossil fuel combustion,
      obtained in this study were substantially lower than in the previous
      investigation (2000) conducted in the area of Belgrade. The level of
      concentrations for V, Cr, Ni, and As in moss from this study correlated to those
      measured for neighboring countries, and were several times higher than the base
      level data from low polluted areas. The level of accumulated elements in both
      investigated moss genera were similar and all studied species could be combined
      for biomonitoring purposes in urban areas.

PMID- 16957842
TI  - Temporal trends of young-of-year fishes in Lake Erie and comparison of diel
      sampling periods.
AB  - We explored temporal trends of young-of-year (YOY) fishes caught in bottom trawl
      hauls at an established offshore monitoring site in Lake Erie in fall during 1961
      2001. Sampling was conducted during morning, afternoon, and night in each year.
      Catches per hour (CPH) of alewife (Alosa pseudoharengus) YOY were relatively low
      and exhibited no temporal trend. This result was consistent with the species'
      intolerance to Lake Erie's adverse winter water temperatures. Gizzard shad
      (Dorosoma cepedianum) YOY decreased sharply after 1991, which was consistent with
      recent oligotrophication of the lake. Following the establishment in 1979 and
      rapid increase of white perch (Morone americana) YOY, white bass (Morone
      chrysops) and freshwater drum (Aplodinotus grunniens) YOY decreased. Trout-perch
      (Percopsis omiscomaycus) YOY decreased during 1986-1991, but recovered to
      previous levels during 1991-2001. The recovery coincided with the resurgence of
      mayflies (Ephemoptera) in the lake. CPH of spottail shiner (Notropis hudsonius)
      and emerald shiner (N. atherinoides) YOY exhibited no temporal trend between 1961
      and the late 1970s to early 1980s. CPH of yellow perch (Perca flavescens) YOY
      decreased during 1961-1988, and walleye (Sander vitreum) YOY increased overall
      during the time series. These observations were consistent with published studies
      of adults in the region. CPH of 4 of the 10 species of YOY considered were
      greatest during night. CPH for walleye YOY was higher in the morning than in the
      afternoon, but there was no significant difference between night and morning
      abundances. The results suggest that (1) CPH of YOY fishes may be a useful
      monitoring tool for Lake Erie, and (2) offshore monitoring programs that do not
      include night sampling periods may underestimate recruitment for several common
      species.

PMID- 16957843
TI  - Critical sampling points methodology: case studies of geographically diverse
      watersheds.
AB  - Only with a properly designed water quality monitoring network can data be
      collected that can lead to accurate information extraction. One of the main
      components of water quality monitoring network design is the allocation of
      sampling locations. For this purpose, a design methodology, called critical
      sampling points (CSP), has been developed for the determination of the critical
      sampling locations in small, rural watersheds with regard to total phosphorus
      (TP) load pollution. It considers hydrologic, topographic, soil, vegetative, and
      land use factors. The objective of the monitoring network design in this
      methodology is to identify the stream locations which receive the greatest TP
      loads from the upstream portions of a watershed. The CSP methodology has been
      translated into a model, called water quality monitoring station analysis
      (WQMSA), which integrates a geographic information system (GIS) for the handling
      of the spatial aspect of the data, a hydrologic/water quality simulation model
      for TP load estimation, and fuzzy logic for improved input data representation.
      In addition, the methodology was purposely designed to be useful in diverse rural
      watersheds, independent of geographic location. Three watershed case studies in
      Pennsylvania, Amazonian Ecuador, and central Chile were examined. Each case study
      offered a different degree of data availability. It was demonstrated that the
      developed methodology could be successfully used in all three case studies. The
      case studies suggest that the CSP methodology, in form of the WQMSA model, has
      potential in applications world-wide.

PMID- 16957844
TI  - The ecological condition of Gulf of Mexico resources from Perdido Key to Port St.
      Joe, Florida, USA: part I. coastal beach resources.
AB  - Using the approach established by EPA's Environmental Monitoring and Assessment
      Program (EMAP), a shoreline monitoring survey was conducted in August and
      September 1999, encompassing the Florida Panhandle from Perdido Key, Florida to
      Port St. Joe, Florida. The objective of this survey was to demonstrate the use of
      a probabilistic survey for monitoring and estimating the condition of swimmable
      beach areas. Thirty stations were sampled using a probabilistic sampling design.
      Hydrographic data were collected in addition to samples for water chemistry.
      Bacterial indicators, enterococci and fecal coliforms, were enumerated from the
      water according to the EPA Beaches Environmental Assessment Closure and Health
      (BEACH) Program and Florida state guidelines. Additional criteria for site
      condition included the presence or absence of primary and secondary dunes,
      anthropogenic debris and vegetation. Based on EMAP evaluation guidelines and
      Florida state criteria, a baseline assessment of the condition of the Gulf of
      Mexico beach resources surveyed is presented.

PMID- 16957846
TI  - Implementation of soil survey and analyses for promoting watershed modelling
      applications.
AB  - Soil is an important component of a watershed. Understanding soils and their
      interactions with the other components are, thus, considered to be critical and
      essential for conservation of resources and management of the watershed.
      Development of soil sampling and analysis programs are crucial for these
      purposes. Site-specific soil data are needed to identify current soil
      characteristics, as well as to validate datasets gathered for watershed-scale
      modelling of non-point sources (NPS) of pollutants arising from various land-use
      activities, hydrodynamics and water quality. The Koycegiz Lake-Dalyan Lagoon
      watershed, located in the southwest of Turkey along the Mediterranean Sea Coast,
      was selected as the study area for watershed modelling purposes. Development of
      soil sampling plans, their practical optimization, soil analyses and
      interpretation are presented in this article. The soil analyses conducted include
      physical, chemical and specific soil characteristics. Within the framework of
      this study, soil fertility parameters are presented and evaluated. Such an
      approach used is recommended for especially developing countries where up-to-date
      data sets are not fully available and/or centrally publicized.

PMID- 16957845
TI  - Physical and sanitary quality of hand-dug well water from oil-producing area of
      Nigeria.
AB  - The physical (pH, Dissolved Solids, Dissolved Oxygen, conductivity, water depth
      temperature) and bacteriological (Total coliforms, Faecal coliforms)
      characteristics of 22 hand-dug wells in oil-rich Niger Delta of Nigeria were
      investigated. All coliforms counts (Log(10) MPN/100 ml) varied from well to well
      ranging from 0 to 6.0 although faecal coliform counts were markedly lower (0-3.5
      vs 1.0-6.0). When both seasons were compared, faecal coliform counts were
      significantly higher (t test; P < 0.05) during the wet season whereas no
      significant difference was observed in respect of total coliforms. Unlike the
      total coliforms, faecal coliform counts increased in wells close to septic tanks
      during the wet season. Although a declining trend was observed during the wet
      season, the values of the physical parameters were within WHO limits. The pH was
      slightly acidic (Mean +/- SD: dry season, 6.04 +/- 0.66; wet, 6.43 +/- 0.62) and
      may be attributed to emissions from gas flaring and petroleum refining
      activities, which is common in the area. While the total coliform counts
      reflected the unsanitary habits of the well users, the detection of faecal
      coliforms exceeding recommended numbers in 63% of the wells render them unfit for
      domestic use. The public health implication is obvious considering the increasing
      number of people using the wells due to the rapid urbanization of the oil-rich
      region.

PMID- 16957847
TI  - The contribution of Acadia PRIMENet research to science and resource management
      in the National Park Service.
AB  - Acadia National Park was one of the 14 sites included in the Park Research and
      Intensive Monitoring of Ecosystems network (PRIMENet). For eight years the EPA
      monitored ultraviolet (UV) radiation at this site, with the National Park Service
      (NPS) sponsoring a total climate and air monitoring station. Under the auspices
      of PRIMENet, research projects were initiated that investigated the effects of UV
      on amphibians, determined watershed mass balances, and developed a model of
      deposition along an elevational gradient. The monitoring data and research
      results have been used by park management to protect vegetation and water
      resources from ozone and deposition. These data are now being used to develop a
      "vital signs" monitoring program under the NPS' Inventory and Monitoring Program.
      These data sets have been used in regional, national and international programs
      to protect human health and resources from air pollution. Public outreach has
      been accomplished through web site resources and via the Schoodic Education and
      Research Center.

PMID- 16957848
TI  - Mercury in tree swallow food, eggs, bodies, and feathers at Acadia National Park,
      Maine, and an EPA superfund site, Ayer, Massachusetts.
AB  - We monitored nest boxes during 1997-1999 at Acadia National Park, Mt. Desert
      Island, ME and at an old-field site in Orono, ME to determine mercury (Hg) uptake
      in tree swallow (Tachycineta bicolor) eggs, tissues, and food boluses. Also, in
      1998-1999 we monitored nest boxes at Grove Pond and Plow Shop Pond at a U.S.
      Environmental Protection Agency Superfund site in Ayer, MA. We recorded breeding
      success at all locations. On average among locations, total mercury (THg)
      biomagnified 2 to 4-fold from food to eggs and 9 to 18-fold from food to
      feathers. These are minimum values because the proportion of transferable methyl
      mercury (MeHg) of the THg in insects varies (i.e., 35%-95% of THg) in food
      boluses. THg was highest in food boluses at Aunt Betty Pond at Acadia, whereas
      THg in eggs was highest at the Superfund site. A few eggs from nests at each of
      these locations exceeded the threshold (i.e., 800-1,000 ng/g, wet wt.) of
      embryotoxicity established for Hg. Hatching success was 88.9% to 100% among
      locations, but five eggs failed to hatch from 4 of the 11 clutches in which an
      egg exceeded this threshold. MeHg in feathers was highest in tree swallows at
      Aunt Betty Pond and the concentration of THg in bodies was related to the
      concentration in feathers. Transfer of an average of 80%-92% of the Hg in bodies
      to feathers may have enhanced nestling survival. Residues of Hg in tissues of
      tree swallows in the Northeast seem higher than those of the Midwest.

PMID- 16957849
TI  - Behaviour and quantification studies of terbacil and lenacil in environmental
      samples using cyclic and adsorptive stripping voltammetry at hanging mercury drop
      electrode.
AB  - The cyclic voltammograms of terbacil and lenacil at the hanging mercury drop
      electrode showed a single well defined four electron irreversible peak in
      universal buffer of pH 4.0 for both compounds. The peak potentials were shifted
      to more negative values on the increase of pH of the medium, implying the
      involvement of protons in the electrode reaction and that the proton transfer
      reaction precedes the proper electrode process. The four electron single peak may
      be attributed to the simultaneous reduction of carbonyl groups present in 2 and 4
      in pyrimidine ring of terbacil and lenacil to the corresponding hydroxy
      derivative. Based on the interfacial adsorptive character of the terbacil and
      lenacil onto the mercury electrode surface, a simple sensitive and low cost
      differential pulse adsorptive stripping voltammetric procedure was optimized for
      the analysis of terbacil and lenacil. The optimal operational conditions of the
      proposed procedure were accumulation potential E (acc) = -0.4 V, accumulation
      time t (acc) = 80 s, scan rate = 40 mV s(-1), pulse amplitude = 25 mV using a
      universal buffer pH 4.0 as a supporting electrolyte. The linear concentration
      range was found to be 1.5 x 10(-5) to 1.2 x 10(-9) mol/l and 1.5 x 10(-5) to 2.5
      x 10(-8) mol/l with the lower detection limit of 1.22 x 10(-9) and 2.0 x 10(-8)
      mol/l. The correlation coefficient and relative standard deviation values are
      found to be 0.942, 0.996, 1.64% and 1.23%, respectively, for 10 replicants. The
      procedure was successfully applied for determination of terbacil and lenacil in
      formulations, mixed formulations, environmental samples such as fruit samples and
      spiked water samples.

PMID- 16957850
TI  - Preconcentration technique for the determination of trace elements in natural
      water samples by ICP-AES.
AB  - A procedure was developed for the determination of Cd, Cu, Zn, Co, Ni, Mn, Pb and
      Mo in water samples by inductively coupled plasma atomic emission spectrometry
      (ICP-AES) after preconcentration on a morpholine dithiocarbamate (mor-DTC)
      supported by bagasse (Saccharam aphisinaram). The sorbed elements were
      subsequently eluted with 4,M HNO3 and the acid eluates were analysed by ICP-AES.
      The influence of various parameters such as pH, flow rate of sample, eluent
      concentration, volume of the sample and volume of eluent were investigated to
      enhance the sensitivity of the present method. A 20,mL disposable syringe served
      as preconcentration column. Under the optimal conditions Cd, Cu, Zn, Co, Ni, Mn,
      Pb and Mo in aqueous sample was concentrated about 100-fold. The sorption
      recoveries of elements were higher than 99.6%. The method is also applied for the
      analysis of natural and spiked water samples.

PMID- 16957851
TI  - Monitoring the formation of trihalomethanes in the effluents from a shrimp
      hatchery.
AB  - Formation of trihalomethanes (THM) was monitored at the Laboratorio de Camaroes
      Marinhos (LCM) from the Universidade Federal de Santa Catarina. THM could be
      present because chlorinated effluents from disinfection are discharged from the
      different hatchery rooms. THM quantification was done through an analytical
      methodology using Purge&Trap coupled with a gas chromatograph equipped with an
      electron capture detector. Relative standard deviation (RSD), limit of detection
      (LOD) and limit of quantification (LOQ) for the methodology corresponded to the
      ranges of 8-17%; 0.01-0.03 microg L(-1) and 0.03-0.08 microg L(-1), respectively.
      Linear working range was of 0.1-8.0 microg L(-1) for all compounds. Enrichment
      and recovery method was applied to evaluate possible matrix effects and the
      results varied from 71.2% to 107.9%. LCM was monitored between August and
      December, 2004. This study showed that THM did not increase with the increase in
      postlarvae production and also that the aquatic life and the surrounding
      environment were not affected.

PMID- 16957852
TI  - The orientation of water quality variation from the metropolis river-Huangpu
      River, Shanghai.
AB  - The Huangpu River supplies eighty percent of daily water used for life and
      industry for about 20 million people in Shanghai, China. Industry and human
      sewerage from the metropolis is mainly released into the Huangpu River, which
      flows past the Shanghai city area. The pollution caused by city life and
      production in the Huangpu River has occurred for years. In this paper, the
      contents of heavy metals (Cu, Pb, Cr, Cd, and Hg), total organic carbon (TOC),
      and polynuclear aromatic hydrocarbons (PAHs) in the Huangpu River are discussed.
      Data from environmental monitoring from 1991 to 2002 are compared to understand
      the variation and trends of the pollution. Results indicate that metals have been
      reduced efficiently, but organic pollutants develop in aggravating trend as human
      sewage increase. The variation of the organic pollutant concentration, which are
      lower than other similar river's of China, US, and Canada, in the Huangpu River
      suggests that the organic pollution maybe a problem of water quality evolvement
      in metropolis river protection, which should be accentuated in the world today.

PMID- 16957853
TI  - Drought-induced sulphate release from a wetland in south-central Ontario.
AB  - Increased sulphate (SO(4)) export from wetlands following summer droughts in
      central Ontario, Canada has been associated with the delayed chemical recovery of
      downstream surface waters following decreased sulphur (S) emissions. Prolonged
      summer droughts result in a decrease or cessation of stream flow, declines in
      wetland water table level and oxidation of reduced S compounds to SO(4), which is
      subsequently flushed into drainage streams when stream flow resumes. Sulphate
      input-output budget calculations (1983-1995 and 1999-2001) at a conifer Sphagnum
      swamp in the Plastic Lake catchment, indicate that SO(4) is retained in most
      years but is exported on a net basis following particularly severe summer
      droughts that result in the cessation of stream flow for more than 54 days (95%
      CI: 41-72 days). Hindcast calculations using long-term (1916-2000) stream
      discharge records from a nearby station indicate that while droughts occurred
      frequently in south-central Ontario over the past 85 years, sufficiently dry
      conditions to cause net SO(4) export occurred in only 18 of the past 85 years,
      and indicate a cumulative positive SO(4) balance for the swamp (i.e. net SO(4)
      retention). Furthermore, the S pool at the Plastic Lake swamp has been estimated
      to be approximately 1500 kg S/ha in the upper 40 cm peat layer, which is large
      compared to the amount of net SO(4) export that occurs even in years with
      particularly dry summers (e.g. -43 kg S/ha in 1987/88). Together, these data
      suggest that the wetland S pool at Plastic Lake has not been depleted by previous
      droughts and will continue to sustain episodic drought-related SO(4) export for
      the foreseeable future.

PMID- 16957854
TI  - Eutrophication status of marine environment of Mumbai and Jawaharlal Nehru ports.
AB  - The marine environment of Mumbai and Jawaharlal Nehru ports was monitored for
      some environmental and biological parameters during three different periods
      between 2001 and 2002. The results are compared with the records available since
      1960s. With the passage of time the environmental status underwent changes,
      probably due to the increase in anthropogenic activities in the metropolis. The
      nutrient level especially the nitrate concentration has increased gradually over
      the years with a simultaneous decrease in dissolved oxygen, indicating increase
      in the biological activity. Characterization of this environment based on
      Assessment of Estuarine Trophic Status (ASSETS) model indicates that the current
      status is poor and may get worsen in future if no appropriate management policies
      are put into place.

PMID- 16957855
TI  - Monitoring pollution in river Mures, Romania, Part III: biochemical effect
      markers in fish and integrative reflection.
AB  - Along a downstream stretch of River Mures, Romania, adult males of two feral fish
      species, European chub (Leuciscus cephalus) and sneep (Chondrostoma nasus) were
      sampled at four sites with different levels of contamination. Fish were analysed
      for the biochemical markers hsp70 (in liver and gills) and hepatic EROD activity,
      as well as several biometrical parameters (age, length, wet weight, condition
      factor). None of the biochemical markers correlated with any biometrical
      parameter, thus biomarker reactions were related to site-specific criteria. While
      the hepatic hsp70 level did not differ among the sites, significant elevation of
      the hsp70 level in the gills revealed proteotoxic damage in chub at the most
      upstream site, where we recorded the highest heavy metal contamination of the
      investigated stretch, and in both chub and sneep at the site right downstream of
      the city of Arad. In both species, significantly elevated hepatic EROD activity
      downstream of Arad indicated that fish from these sites are also exposed to
      organic chemicals. The results were indicative of impaired fish health at least
      at three of the four investigated sites. The approach to relate biomarker
      responses to analytical data on pollution was shown to fit well the recent EU
      demands on further enhanced efforts in the monitoring of Romanian water quality.

PMID- 16957856
TI  - Persistent organochlorine pesticide residues in soil and surface water of
      northern Indo-Gangetic alluvial plains.
AB  - This study reports the concentration levels and distribution pattern of the
      organochlorine pesticide (OCPs) residues in the soil and surface water samples
      collected from the northern Indo-Gangetic alluvial plains. A total of 31 soil and
      23 surface water samples were collected from the study region in Unnao district
      covering an area of 2150 km(2) and analyzed for aldrin, dieldrin, endrin, HCB,
      HCH isomers, DDT isomers/metabolites, endosulfan isomers (alpha and beta),
      endosulfan sulfate, heptachlor and its metabolites, alpha-chlordane, gamma
      chlordane and methoxychlor. In both the soil and surface water samples beta- and
      delta-isomers of HCH were detected most frequently, whereas, methoxychlor was the
      least detected pesticide. The results showed contamination of soil and surface
      water of the region with several persistent organic pesticides. The total OCPs
      level ranged from 0.36-104.50 ng g(-1) and 2.63-3.72 microg L(-1) in soil and
      surface water samples, respectively.

PMID- 16957857
TI  - Does seston size structure reflect fish-mediated effects on water quality in a
      degraded semiarid wetland?
AB  - This study evaluates whether the size structure of seston (the sum of living and
      nonliving particles in the water column) reflects the effects of fish on wetland
      water quality. Using enclosures, we measured water quality and zooplankton
      community structure in the presence and absence of two fish species with distinct
      foraging strategies [benthivorous carp (Cyprinus carpio) and planktivorous
      mosquitofish (Gambusia holbrooki)]. Seston collected from the enclosures was
      counted and sized automatically with a Coulter counter, and the size structure in
      the range of 1-60 microm was modelled using the underlying Pareto distribution of
      particles. Only Cyprinus contributed to a loss of water quality (increased
      nutrient levels, algal and non-algal turbidity, hypoxia), while both fish species
      changed zooplankton community composition compared to fishless controls. However,
      these changes were not reflected in parameters [goodness of fit (r (2)) and
      parameter c (slopes)] of Pareto models. Multivariate statistics suggest that
      seston size structure responded more to environmental gradients related to water
      depth but the relationships were also weak. Our overall result contrasts with the
      regulation of size spectra constructed from living organisms. Although seston
      integrates many structural and functional features of the water column, the lack
      of strong relationships between Pareto model parameters and water quality
      suggests that a size-based approach to characterise seston structure has a
      limited potential for assessing biota-mediated effects in wetlands in a
      straightforward manner.

PMID- 16957858
TI  - Petroleum contaminated soil in Oman: evaluation of bioremediation treatment and
      potential for reuse in hot asphalt mix concrete.
AB  - This paper presents a study that aims at evaluating the leaching characteristics
      of petroleum contaminated soils as well as their application in hot mix asphalt
      concrete. Soil samples are environmentally characterized in terms of their total
      heavy metals and hydrocarbon compounds and leachability. The total petroleum
      hydrocarbon (TPH) present in the PCS before and after treatment was determined to
      be 6.8% and 5.3% by dry weight, indicating a reduction of 1% in the TPH of PCS
      due to the current treatment employed. Results of the total heavy metal analysis
      on soils indicate that the concentrations of heavy metals are lower when
      extraction of the soil samples is carried out using hexane in comparison to TCE.
      The results show that the clean soils present in the vicinity of contaminated
      sites contain heavy metals in the following decreasing order: nickel (Ni),
      followed by chromium (Cr), zinc (Zn), copper (Cu), lead (Pb), and vanadium (V).
      The current treatment practice employed for remediation of the contaminated soil
      reduces the concentrations of nickel and chromium, but increases the
      concentrations of all remaining heavy metals.

PMID- 16957859
TI  - Computer inference of network of ecological interactions from sampling data.
AB  - Both direct and indirect ecological interactions may occur in an ecosystem with
      large numbers of taxa. Traditional food web technique is a popular tool to
      measure the quality and health of the environment. Much of works must be done
      before constructing a food web for an ecosystem especially with many taxa. This
      food web is generally specific for some ecological interactions and fixed for a
      set of given species. It is therefore not an effective method for dynamic and
      prompt assessment of environment. Ecological interactions and their interactive
      intensity may be detected by sampling biological taxa in the field and by
      detecting various between-taxa distances or similarities. Network may clearly
      exhibit the complex interactions among biological taxa. Statistic tests on
      various distance or similarity measures and computer designs are required to
      infer the {network. We develop an algorithm and software to infer the network of
      direct or indirect ecological interactions in ecosystem. It is a prompt and
      effective tool in monitoring and assessment of the environment. A redundant
      network may be inferred and drawn by computer based on the statistic tests on
      sampling data or the pathway information given in HTML file. Dominant taxa may be
      found in the network. In total of 16 distance and similarity measures, including
      Euclidean distance, Manhattan distance, Pearson correlation, partial correlation,
      point correlation, linkage coefficients, Jaccard coefficient etc., are provided
      to detect taxa pairs with significant parametric or nonparametric similarities,
      based on randomization tests and ordinary statistic tests. Criteria to use
      distance and similarity measures are discussed.

PMID- 16957860
TI  - Assessment of spatial variability in some soil properties as related to soil
      salinity and alkalinity in Bafra plain in northern Turkey.
AB  - The objectives of this study were to assess the variability in soil properties
      affecting salinity and alkalinity, and to analyze spatial distribution patterns
      of salinity (EC) and alkalinity (ESP) in the plain, which was used irrigation
      agriculture with low quality waters. Soil samples were collected from 0-30 cm, 30
      60 cm, 60-90 cm and 90-120 cm soil depths at 60 sampling sites. Soil pH had the
      minimum variability, and hydraulic conductivity (Ks) had the maximum variability
      at all depths. The mean values of pH, EC, ESP and Ks increased while the mean
      values of CEC decreased with soil depth. Values pH, EC and ESP were generally
      high in the east and northeastern sides. Soil properties indicated moderate to
      strong spatial dependence. ESP and pH were moderately spatially dependent for
      three of the four depths, EC exhibited moderate spatial dependence for one of the
      four depths, CEC had a moderate spatial dependence at all depths, and Ks
      exhibited a strong spatial dependence. EC, CEC, and ESP were considerably
      variable in small distances. The spatial variability in small distances of EC,
      CEC, pH and ESP generally increased with depth. All geostatistical range values
      were greater than 1230 m. It was inferred that the strong spatial dependency of
      soil properties would be resulted in extrinsic factors such as ground water
      level, drainage, irrigation systems and microtopography.

PMID- 16957861
TI  - Contaminant exposure in outmigrant juvenile salmon from Pacific Northwest
      estuaries of the United States.
AB  - To better understand the dynamics of contaminant uptake in outmigrant juvenile
      salmon in the Pacific Northwest, concentrations of polychlorinated biphenyls
      (PCBs), DDTs, polycylic aromatic hydrocarbons (PAHs) and organochlorine
      pesticides were measured in tissues and prey of juvenile chinook and coho salmon
      from several estuaries and hatcheries in the US Pacific Northwest. PCBs, DDTs,
      and PAHs were found in tissues (whole bodies or bile) and stomach contents of
      chinook and coho salmon sampled from all estuaries, as well as in chinook salmon
      from hatcheries. Organochlorine pesticides were detected less frequently. Of the
      two species sampled, chinook salmon had the highest whole body contaminant
      concentrations, typically 2--5 times higher than coho salmon from the same sites.
      In comparison to estuarine chinook salmon, body burdens of PCBs and DDTs in
      hatchery chinook were relatively high, in part because of the high lipid content
      of the hatchery fish. Concentrations of PCBs were highest in chinook salmon from
      the Duwamish Estuary, the Columbia River and Yaquina Bay, exceeding the NOAA
      Fisheries' estimated threshold for adverse health effects of 2400 ng/g lipid.
      Concentrations of DDTs were especially high in juvenile chinook salmon from the
      Columbia River and Nisqually Estuary; concentrations of PAH metabolites in bile
      were highest in chinook salmon from the Duwamish Estuary and Grays Harbor.
      Juvenile chinook salmon are likely absorbing some contaminants during estuarine
      residence through their prey, as PCBs, PAHs, and DDTs were consistently present
      in stomach contents, at concentrations significantly correlated with contaminant
      body burdens in fish from the same sites.

PMID- 16957862
TI  - Arsenic and other metal contamination of groundwaters in the industrial area of
      Thessaloniki, Northern Greece.
AB  - In groundwater, used for drinking water supply in the greater industrial area of
      Thessaloniki, in Northern Greece, concentrations of total arsenic exceeded the
      WHO provisional guideline value and the EU maximum contaminant level (MCL) of 10
      microg/L. The concentration of total arsenic was in the range between 4-130
      microg/L, whereas the median value was 36 microg/L and the average concentration
      46 microg/L. Nine out of the eleven wells contained total arsenic at
      concentration higher than 10 microg/L and it should be stressed that 6 of them
      contain arsenic at concentrations between 10 (new MCL) and 50 microg/L (previous
      MCL). The examined groundwaters were found to contain elevated concentrations of
      manganese and phosphate. Arsenic had a positive correlation with the pH,
      indicating the possible effect of pH on arsenic mobilisation. These findings
      emerge the problem of contamination from arsenic, since, according to the EU
      directive 98/83, all drinking water sources within the European Union should have
      achieved compliance with the new limits by 12/2003, implying that the situation
      requires urgent remedial action.

PMID- 16957863
TI  - A knowledge-based approach to environmental biomonitoring.
AB  - This paper presents the design, development and implementation of an integrated
      GIS-controlled knowledge-based system for environmental monitoring applications,
      utilizing indigenous flora for assessing quality. The system gathers and combines
      geographical, ecological, and physicochemical data of organisms' response to
      pollution within an intelligent computer program that (a) recognises groups of
      indigenous species suitable for long-term monitoring of a specific pollutant or a
      combination of pollutants, (b) estimates the ambient concentration of
      pollutant(s) from the population of the species comprising the bioindicator group
      and (c) provides biomonitoring capacity indices at national and
      international/transboundary levels. Significantly, a novel system in the form of
      a rational framework at the conceptual design level has been developed, that
      actually contributes towards achieving a cost-effective long-term biomonitoring
      program, with the flexibility to counter on-course any (anticipated or not)
      variations/modifications of the surveillance environment: the scheme assumes a
      robust dynamic cooperation between instrumental and biomonitoring systems, with a
      view to minimise uncertainty and monitoring costs and increase reliability of
      pollution control and abatement, aiming eventually at the shifting, partially or
      totally, from instrumental to natural monitoring. The proposed approach is
      presently implemented at pilot-scale for establishing a biomonitoring network at
      a large industrial area in Greece. The results obtained indicate that a cost
      effective program can be only attained and maintained under a suitable
      financial/organizational scheme at the macro level, whereas the micro level
      viability strongly depends upon careful management of human resources and fixed
      assets.

PMID- 16957865
TI  - Alberta biodiversity monitoring program - monitoring effectiveness of sustainable
      forest management planning.
AB  - A conceptual model of sustainable forest management is described based on three
      connected and necessary components: Policy/Strategic Planning, Operational
      Planning, and Effectiveness Monitoring/Science. Alberta's proposed Forest
      Management Planning Standard is described as an example of operational planning.
      The standard utilizes coarse and fine filter approaches to conserving
      biodiversity and sets requirements for implementation monitoring. The Alberta
      Biodiversity Monitoring Program (ABMP) is described as an example of
      effectiveness monitoring supporting Operational Planning. The ABMP is a rigorous
      science-based initiative that is being developed to monitor and report on
      biodiversity status and trends throughout the province of Alberta, Canada. The
      basic survey design consists of 1656 sites, 20 km apart, evenly spaced on a grid
      pattern across Alberta. Sites will be sampled over a five-year period at a rate
      of 350 sites/year. Standardized sampling protocols will be used to cover a broad
      range of species and habitat elements within terrestrial and aquatic
      environments, as well as broader landscape-level features. Trends and
      associations detected by ABMP products will be validated through cause-effect
      research. ABMP focuses research on critical issues and informs both operational
      planning and the development of policy and strategic-level plans. The Alberta
      Forest Management Planning Standard and the ABMP are described as key components
      to implementing resource planning based on ecosystem management principles.

PMID- 16957864
TI  - Study of geochemical association of some trace metals in the sediments of Chilika
      lake: a multivariate statistical approach.
AB  - In order to establish the natural processes and geochemical factors responsible
      for enrichment of trace metal ions (Cu, Co, Ni, Zn and Cr) with respect to
      textural parameters (sand, silt and clay weight percentages) along with depth,
      multivariate statistical approach has been carried out for sediments in different
      water zones of Chilika lake, the largest brackish water lagoon in Asia. The
      rotated varimax factor results reveal that Cobalt enrichment is controlled by
      both textural parameters as well as adsorption mechanism. In fresh and saline
      water region, textural parameters and in mixed water, adsorption phenomenon
      predominates. Zn in fresh water is related to clay, whereas it is in adsorbed
      state in mixed water. Cu in fresh water sediments is in absorbed state and in
      mixed water it is related to depth and Co concentration. Cr does not show any
      specific association in fresh water, but in both mixed and saline water it is
      associated with clay minerals. Although both textural parameters and adsorption
      mechanism play an important role for the enrichment of trace metal ions in these
      lagoonal sediments, their relative importance varies with specific metal ions as
      well as the water quality. Sequential extraction technique was used to
      characterize the various forms of metals in the < 63 micro size sediments of
      Chilika lake. The concentrations determined indicated selective accumulation of
      the various metals in the different phases with spatial variability in different
      water zones. Slightly higher availability of Co and Zn near Balugaon township in
      exchangeable phase may be related to anthropogenic activities. Among the non
      lithogenous (NL) phases, reducible phase associated with higher concentration of
      Ni, Cu and Cr. Organic bound Zn and Co contributed highest percentages among NL
      fractions. Residual fraction contributed more than 50% in most of the cases,
      reflected the predominance of physical weathering, high erosion rate along the
      drainage basin.

PMID- 16957866
TI  - Ecotoxicological classification of the Berlin river system using bioassays in
      respect to the European Water Framework Directive.
AB  - Bioassays as well as biochemical responses (biomarkers) in ecosystems due to
      environmental stress provide us with signals (environmentally signalling) of
      potential damage in the environment. If these responses are perceived in this
      early stage in ecosystems, the eventual damage can be prevented. Once ecosystem
      damage has occurred, the remedial action processes for recovery could be
      expensive and pose certain logistical problems. Ideally, "early warning signals"
      in ecosystems using sensing systems of biochemical responses (biomarkers) would
      not only tell us the initial levels of damage, but these signals will also
      provide us with answers by the development of control strategies and
      precautionary measures in respect to the European Water Framework Directive
      (WFD). Clear technical guidelines or technical specifications on monitoring are
      necessary to establish and characterise reference conditions for use in an
      ecological status classification system for surface water bodies. For the
      Ecotoxicological Risk Assessment (ERA) of endocrine effects we used an approach
      of the exposure - dose - response concept. Based on the "Ecototoxicological
      Classification System of Sediments" that uses pT-values to classify effects in
      different river systems, we transferred the bio-monitoring data to the five-level
      ecological system of the WFD. To understand the complexity of the structure of
      populations and processes behind the health of populations, communities and
      ecosystems an ERA should establish links between natural factors, chemicals, and
      biological responses so as to assess causality. So, our ecological monitoring
      assessment has incorporated exposure & effects data.

PMID- 16957867
TI  - The comparison of phosphorus pools from the sediment in two bays of Lake Dianchi
      for cyanobacterial bloom assessment.
AB  - The different pools in the sediment from two bays with different scales of
      cyanobacterial bloom were studied to assess the trophic status. With large scale
      of cyanobacterial bloom in Haigeng bay the concentrations of different phosphorus
      fractions were higher than the corresponding concentrations in Macun bay, and
      especially WSP and AAP are the most evident, which indicates that there are more
      available and potential available phosphorus in Haigeng bay. The adsorption
      experiment also shows that the sediment in Haigeng bay is more saturated than
      that in Macun bay. Haigeng bay can be faced with the more serious ecological
      danger. Furthermore the death and deposit of a mass of algae can contribute to
      phosphorus released from sediment and help to the breakout of newborn
      cyanobacterial blooms.

PMID- 16957868
TI  - Immunological biomarkers of ageing in man: changes in both innate and adaptive
      immunity are associated with health and longevity.
AB  - Scientific and clinical advances in the last century have led to increased
      numbers of individuals living to older ages. Thus a major concern is how to live
      these years with a high quality of life. The ageing immune system is less well
      able to cope with infectious diseases than the youthful immune system probably as
      a consequence of altered immune response to pathogens. Thus, both innate and
      adaptive immune responses show age-related changes that could be decisive for
      healthy ageing and survival. Longitudinal studies in healthy elderly have allowed
      the definition of the ''immune risk phenotype" (IRP) a predictor of mortality in
      elderly individuals that is based on several parameters of the adaptive immune
      response. Here, we hypothesize that failures in innate immunity observed in frail
      elderly are related to those alterations described in adaptive immunity defined
      as the IRP. It will be important to include assays of NK cell markers and
      functions in future longitudinal studies in order to investigate this point in
      detail as well as to consider the trace element zinc as an essential co-factor
      for optimal NK cell activity.

PMID- 16957869
TI  - Daily consumption of green tea catechin delays memory regression in aged mice.
AB  - Almost all elderly people show brain atrophy and cognitive dysfunction, even if
      they are saved from illness, such as cardiac disease, malignancy and diabetes.
      Prevention or delay of brain senescence would therefore enhance the quality of
      life for older persons. Because oxidative stress has been implicated in brain
      senescence, we investigated the effects of green tea catechin (GT-catechin), a
      potential antioxidant, in senescence-accelerated (SAMP10) mice. The mouse is a
      model of brain senescence with short life span, cerebral atrophy and cognitive
      dysfunction. Mice were fed water containing 0.02% GT-catechin from 1- to 15-month
      old. The mean dose was about 35 mg/kg/day. We found that daily consumption of GT
      catechin prevented memory regression and DNA oxidative damage in these mice. GT
      catechin did not prolong the lifetime of SAMP10 mice, but it did delay brain
      senescence. These findings suggest that continued intake of GT-catechin might
      promote healthy ageing of the brain in older persons.

PMID- 16957871
TI  - The preservation of tissues for transplantation.
AB  - This paper is a written version of a lecture given during the celebration of
      Professor Rudolf Klen's 90th birthday. Dr. Klen played by far the major part in
      the introduction and the development of Tissue Banking in Europe. His concept of
      a tissue bank envisaged the storage of all types of cell, tissue and organ that
      physicians and surgeons might need for the treatment of their patients. There has
      been much progress towards this goal, but still the final objective remains
      elusive. This review of the current position starts with the recognition that
      some tissues are required to comprise or include cells that exhibit all the
      formal characteristics of life if they are to function as grafts, whereas other
      tissues do not. For some tissues, the preservation of mechanical properties is
      crucial: for others it is not. These considerations are crucial for the design of
      preservation methods for specific tissues: bone tendon and skin can provide
      useful grafts in the absence of living cells and this may even be true of cardiac
      valves: the crucial requirement here is that the mechanical properties remain
      intact. Simply freezing at around -80 degrees C may be sufficient. In contrast,
      many cell systems, and all metabolizing organs do require healthy cells to
      function. Cryopreservation is often an effective remedy for isolated cells, for
      example haemopoietic stem cells, but the damaging effects of the formation of ice
      are sufficient to rule out this approach for whole vascularised organs and for
      some tissues too. The damaging mechanisms are discussed, and it is concluded that
      the site of ice crystallization is crucial. Cartilage has hitherto been
      recalcitrant, but we have recently developed a method that permits this tissue to
      be stored at liquid nitrogen temperatures without any ice and with the recovery
      of living cells and intact mechanical properties after storage. Thus, many
      methods are available to help develop tissue banking originally envisioned by Dr.
      Klen.

PMID- 16957870
TI  - Distribution of soluble epoxide hydrolase, cytochrome P450 2C8, 2C9 and 2J2 in
      human malignant neoplasms.
AB  - Soluble epoxide hydrolase (sEH) is a bifunctional enzyme with a C-terminal
      epoxide hydrolase activity and an N-terminal phosphatase activity. Arachidonic
      acid epoxides, previously suggested to be involved in apoptosis, oncogenesis and
      cell proliferation, are generated by cytochrome P450 epoxygenases and are good
      substrates of the sEH C-terminal domain. In addition, the N-terminal phosphatase
      domain hydrolyzes isoprenoid mono- and pyrophosphates, which are involved in cell
      signaling and apoptosis. Here we provide a comprehensive analysis of the
      distribution of sEH, CYP2C8, 2C9 and 2J2 in human neoplastic tissues using tissue
      micro-arrays. The human neoplastic tissue micro-arrays provide a well-controlled
      side by side analysis of a wide array of neoplastic tissues and their surrounding
      normal tissue controls. Many of the neoplastic tissues showed altered expression
      of these enzymes as compared to normal tissues. Altered expression was not
      limited to the neoplastic tissues but also found in the surrounding non
      neoplastic tissues. For example, sEH expression in renal and hepatic malignant
      neoplasms and surrounding non-neoplastic tissues was found to be significantly
      decreased, whereas expression was found to be increased in seminoma as compared
      to normal tissues. Our study warrants further investigation of the role of
      altered expression of these enzymes in neoplastic tissues.

PMID- 16957872
TI  - Estimating the minimum number of judges required for test-centred standard
      setting on written assessments. do discussion and iteration have an influence?
AB  - Absolute standard setting procedures are recommended for assessment in medical
      education. Absolute, test-centred standard setting procedures were introduced for
      written assessments in the Liverpool MBChB in 2001. The modified Angoff and Ebel
      methods have been used for short answer question-based and extended matching
      question-based papers, respectively. Data collected has been analysed to
      investigate whether reliable standards can be achieved for small-scale, medical
      school-based assessments, to establish the minimum number of judges required and
      the effect of a discussion phase on reliability. The root mean squared error
      (RMSE) has been used as a measure of reliability and used to compute 95%
      confidence intervals for comparison to the examination statistics. The RMSE has
      been used to calculate the minimum number of judges required to obtain a
      predetermined minimum level of reliability, and the effect of the number of
      judges and number of items have been examined. Values of the RMSE obtained vary
      from 0.9 to 2.2%. Using average variances across each paper type, the minimum
      number of judges to obtain a RMSE of less than 2% is 10 or more judges before
      discussion or 6 or more judges after discussion. The results indicate that
      including a discussion phase improves the reliability and reduces the minimum
      number of judges required. Decision studies indicate that increasing the number
      of questions included in the assessments would not significantly improve the
      reliability of the standard setting.

PMID- 16957873
TI  - Clinical characteristics and objective living conditions in relation to quality
      of life among community-based individuals of schizophrenia in Hong Kong.
AB  - Quality of life (QOL) has gained importance as an outcome measure for people with
      schizophrenia living in the community following deinstitutionalization. This
      study aims at exploring the effects of clinical characteristics and objective
      living conditions on QOL. In this study, 201 community-based individuals with
      schizophrenia were recruited from five different types of objective living
      conditions comprising long stay care home, halfway house, supported
      hostel/housing, living with family, and living alone. Clinical characteristics
      including cognitive abilities, symptom levels, and community/social functioning
      were assessed by the Allen Cognitive Level Screen, the Scales for the Assessment
      of Negative Symptoms and Positive Symptoms, and the Chinese version of the
      Multnomah Community Ability Scale respectively. The outcome measure of QOL was
      measured by the Chinese version of the WHO Quality of Life Measure. Analysis of
      covariance showed significant differences in community/social functioning,
      cognitive abilities, and negative symptoms; but not in QOL under different
      objective living conditions. Further simultaneous multiple regressions found out
      that community/social functioning was the robust significant predictor of QOL.
      Yet caution should be noted in making the conclusion with the objective living
      condition of long stay care home, as it provides a protective element for the
      perseverance of QOL.

PMID- 16957874
TI  - Optic pit associated serous macular detachment.

PMID- 16957875
TI  - Anatomic outcome of scleral buckling surgery in primary rhegmatogenous retinal
      detachment.
AB  - PURPOSE: To evaluate the factors affecting the anatomic success of treatment of
      retinal detachments (RD) by scleral buckling surgery. METHODS: One-hundred and
      two eyes of 102 patients with rhegmatogenous RD operated on by scleral buckling
      surgery were included in the study. Results were analyzed according to the
      anatomic status of the retina at the most recent follow-up examination. The chi
      squared test was used to determine the relationship between preoperative and
      intraoperative variables and anatomic results, and the relative risk of failure
      was determined for each variable. RESULTS: Retinal reattachment was achieved in
      85 of 102 eyes (82.5%) after initial surgery. The success rate for anatomic
      reattachment was 95% after two operations. After three operations reattachment
      was achieved for 98 eyes (96%). Predictive factors for anatomic failure (P<0.05)
      were the presence of grade C(1) PVR and multiple breaks. CONCLUSION: Grade C(1)
      PVR and multiple breaks were found to be significant risk factors for anatomic
      failure in rhegmatogenous RD treated by conventional buckling surgery.

PMID- 16957876
TI  - Unusual macular lesions in a patient with neurofibromatosis type-1.
AB  - BACKGROUND: Retinal involvement in neurofibromatosis type-1 (NF-1) is rare.
      METHODS: We present a case report of a 49-year-old man with neurofibromatosis who
      developed bilateral macular lesions associated with gradual reduction of visual
      acuity. RESULTS: Electrophysiology revealed an absent pattern electroretinogram.
      Fluorescein angiography demonstrated mottled hyperfluorescence of the maculae in
      the early-phase fluorescein angiogram followed by late staining of the lesions.
      CONCLUSIONS: Our patient had unusual bilateral macular lesions which had some
      features suggestive of adult-onset foveomacular vitelliform dystrophy. To the
      best of our knowledge, there have been no previous reports of such macular
      lesions occurring in association with NF-1.

PMID- 16957877
TI  - The spectrum of Vogt-Koyanagi-Harada disease in Turkey: VKH in Turkey.
AB  - AIM: The aim of this report was to provide a detailed description of the clinical
      features of Vogt-Koyanagi-Harada (VKH) disease in Turkish patients. METHODS: We
      retrospectively analyzed 45 patients diagnosed with VKH disease at seven referral
      centers in Turkey. A standard data acquisition form was used for the analysis of
      demographic and clinical features. RESULTS: The study cohort consisted of 45
      patients (32 female, 13 male) who had a mean age at presentation of 31 years.
      Seven patients (15%) were aged 16 years or younger. Nineteen (42%) patients
      presented in the acute or subacute stage and 26 (58%) in the chronic stage.
      According to the revised diagnostic criteria, nine (20%) patients had the
      complete form of the disease, 23 (51%) had the incomplete form, and 13 (29%) had
      probable VKH disease. All patients had bilateral ocular involvement. Sunset-glow
      fundus was observed in 89% of the patients, pigment clumping in 73%, nummular
      depigmented scars in 71%, cataract in 53%, optic atrophy in 31%, glaucoma in 29%,
      subretinal fibrosis in 22%, choroidal neovascular membranes in 7%, and phthisis
      in 4%. All patients who presented at the acute uveitic stage received systemic
      corticosteroid therapy. Immunosuppressive treatment was employed in 30 (66%)
      patients, which was initiated at the acute uveitic stage in ten (22%) patients.
      Final visual acuity was better than 0.5 in 59% of the patients' eyes, between 0.1
      and 0.5 in 21%, and less than 0.1 in 20%. CONCLUSIONS: VKH disease is rare in
      Turkey. We conclude that the majority of patients with VKH in Turkey do not have
      the complete form of the disease. Based on our results, most patients with VKH
      seem to be late referrals. Ocular complications were common among these patients.

PMID- 16957878
TI  - Microbial keratitis after amniotic membrane transplantation.
AB  - PURPOSE: To determine the incidence of early-onset (<30 days) and late-onset (>30
      days) microbial keratitis after treatment of persistent corneal epithelial
      defects with amniotic membrane transplantation (AMT) utilizing tissue acquired
      from a commercial laboratory or prepared by the institutional eye bank. METHODS:
      A retrospective, non-randomized, sequential, comparative study was performed for
      every patient with a persistent corneal epithelial defect who underwent primary
      AMT at KKESH between January 1, 2003 and June 30, 2004. RESULTS: A total of 142
      AMT procedures were performed for persistent corneal epithelial defects during
      the study period. There were 72 cases using commercially prepared tissue and 70
      cases using locally prepared tissue. The mean patient age was 50.3+/-25.6 years
      (range, 1-104 years). The mean follow up was 6.3+/-5.0 months (range, 1-21
      months). There were no cases of early-onset microbial keratitis in cases in which
      either commercially acquired tissue or locally prepared tissue was used.
      CONCLUSION: Amniotic tissue prepared in a commercial laboratory or by properly
      qualified eye bank personnel may be used for AMT in eyes with persistent corneal
      epithelial defects with minimal risk of microbial keratitis in the first
      postoperative month.

PMID- 16957879
TI  - Physiological effects of constitutive expression of Oilseed Rape Mosaic
      Tobamovirus (ORMV) movement protein in Arabidopsis thaliana.
AB  - Movement proteins (MPs) are non-cell autonomous viral-encoded proteins that
      assist viruses in their cell-to-cell movement. The MP encoded by Tobamoviruses is
      the best characterized example among MPs of non-tubule-inducing plant RNA
      viruses. The MP of Oilseed Rape Mosaic Tobamovirus (ORMV) was transgenically
      expressed in Arabidopsis thaliana, ecotype RLD, under the expression of the 35S
      promoter from Cauliflower Mosaic Virus. Transgenic lines were obtained in sense
      and antisense orientations. One of the sense transgenic lines was further
      characterized turning out to carry one copy of the transgene inserted in the
      terminal region of the right arm of chromosome 1. The constitutive expression of
      ORMV-MP induced mild physiological effects in Arabidopsis. Plants of the
      transgenic line allowed a faster systemic movement of the phloem tracer
      carboxyfluorescein. The tracer was unloaded differentially in different flower
      parts, revealing differential effects of ORMV-MP on phloem unloading in sink
      organs. On the other hand, transgenic Arabidopsis did not show any effect on
      biomass partitioning or sugar availability, effects reported for equivalent
      transgenic solanaceous plants expressing the MP of Tobacco Mosaic Virus, another
      Tobamovirus. Finally, the transgenic Arabidopsis plants were susceptible to ORMV
      infection, although showing milder overall symptoms than non-transgenic controls.
      The results highlight the relevance of the specific host-virus system, in the
      physiological outcome of the molecular interactions established by MPs.

PMID- 16957880
TI  - Generation of trangenic Xenopus laevis using the Sleeping Beauty transposon
      system.
AB  - Using the Sleeping Beauty (SB) transposon system, we have developed a simple
      method for the generation of Xenopus laevis transgenic lines. The transgenesis
      protocol is based on the co-injection of the SB transposase mRNA and a GFP
      reporter transposon into one-cell stage embryos. Transposase-dependent reporter
      gene expression was observed in cell clones and in hemi-transgenic animals. We
      determined an optimal ratio of transposase mRNA versus transposon-carrying
      plasmid DNA that enhanced the proportion of hemi-transgenic tadpoles. The
      transgene is integrated into the genome and may be transmitted to the F1
      offspring depending on the germline mosaicism. Although the transposase is
      necessary for efficient generation of transgenic Xenopus, the integration of the
      transgene occurred by an non-canonical transposition process. This was observed
      for two transgenic lines analysed. The transposon-based technique leads to a high
      transgenesis rate and is simple to handle. For these reasons, it could present an
      attractive alternative to the classical Restriction Enzyme Mediated Integration
      (REMI) procedure.

PMID- 16957881
TI  - The effect of coating single- and double-stranded DNA with the recombinase A
      protein of Escherichia coli on transgene integration in mice.
AB  - Embryo survival and transgene integration rates are two major factors that
      influence the efficiency of transgenic animal production by pronuclear
      microinjection. Recombinase A protein-coated transgenes were compared for
      transgene integration and embryo survival with their non-coated counterparts in
      both single- and double-stranded forms. Murine zygotes were microinjected with a
      large 30 kb alpha(S1)-casein/human lysozyme DNA construct and a small 5.5 kb beta
      lactoglobulin/desaturase DNA construct using four different construct
      preparations for each gene. The preparations included recombinase A protein
      coated, single- and double-stranded DNA constructs and non-coated, single- and
      double-stranded DNA constructs. Using conventional non-coated, double-stranded
      DNA constructs, we obtained a transgene integration efficiency of 1.5% (1352
      embryos transferred produced 20 transgenic pups). The same double-stranded DNA
      constructs coated with recombinase A protein yielded a similar percentage of
      transgene integration (1.1%, 18/1697). Using single-stranded DNA, non-coated
      constructs produced a transgene integration rate of 0.5%, while none of the 1040
      zygotes injected with recombinase A-coated constructs produced transgenic pups.
      While recombinase A protein coating produced no effect on embryo survival, litter
      size or pregnancy rate with double-stranded constructs, a detrimental effect was
      observed on embryo survival (P < 0.001) and pregnancy rate (P < 0.005) with
      recombinase A protein coating of single-stranded human lysozyme DNA constructs. A
      trend toward increased embryo survival (P = 0.054) with no difference in
      pregnancy rate (P > 0.05) was observed with the recombinase A protein coating of
      single-stranded desaturase constructs. These results suggest that recombinase A
      protein coating of single- and double-stranded DNA constructs produced no
      significant differences (P > 0.05) in the efficiency of generating transgenic
      mice with respect to the percentage of transgenic animals born.

PMID- 16957882
TI  - Prokaryotes that grow optimally in acid have purine-poor codons in long open
      reading frames.
AB  - In nucleic acids the N-glycosyl bonds between purines and their ribose sugar
      moities are broken under acid conditions. If one strand of a duplex DNA segment
      were more vulnerable to mutation than the other, then the archaeon Picrophilus
      torridus, with an optimum growth pH near zero, could have adapted by decreasing
      the purine content of that strand. Yet, P. torridus has an optimum growth
      temperature near 60 degrees C, and thermophiles prefer purine-rich codons. We
      found that, as in other thermophiles, high growth temperature correlates with the
      use of purine-rich codons. The extra purines are often in third, non-amino acid
      determining, codon positions. However, as in other acidophiles, as open reading
      frame lengths increase, there is increased use of purine-poor codons,
      particularly those without purines in second, amino acid-determining, codon
      positions. Thus, P. torridus can be seen as adapting (a) to temperature by
      increasing its purines in all open reading frames without greatly impacting
      protein amino acid compositions, and (b) to pH by decreasing purines in longer
      open reading frames, thereby potentially impacting protein amino acid
      compositions. It is proposed that longer open reading frames, being larger
      mutational targets, have become less vulnerable to depurination by virtue of
      pyrimidine for purine substitutions.

PMID- 16957883
TI  - Lateral ball interception: hand movements during linear ball trajectories.
AB  - Part of understanding how acts are coordinated is identifying the information
      that guides movements. In the case of catching a ball within arm's reach, that
      identification has been complicated by empirical disparities concerning hand
      movement reversals during catching. Jacobs and Michaels found unilateral
      reversals in a paradigm in which balls swung down in an arc; this implicated a
      particular optical variable, the ratio of lateral velocity to expansion velocity.
      Montagne et al. reported bilateral reversals when balls approached along a linear
      trajectory, which implicated a different variable, lateral ball position. The
      research reported here attempted to replicate Montagne et al.'s findings. In
      Experiment 1, participants caught balls rolling toward them across a table, under
      full lighting using monocular or binocular viewing; in Experiment 2, participants
      caught luminous balls with a luminous glove in an otherwise dark room. Using
      Montagne et al.'s criterion, we observed no movement reversals in any condition,
      though some aspects of hand movements suggested the relevance of lateral ball
      position. The results of Experiment 3, which asked perceivers to indicate only
      where rods pointed, suggested that lateral position effects were a bias that is
      unrelated to interception. The ratio of lateral velocity to expansion appears to
      be a better variable for explaining hand trajectories in lateral interception.

PMID- 16957884
TI  - Sensorimotor adaptation in response to proprioceptive bias.
AB  - Studies investigating visuo-motor adaptation typically introduce sensory
      conflicts by manipulating visual information (prisms, cursor gains). The purpose
      of the present study was to determine whether similar adaptation would be
      observed when a conflict is created through distortion of the proprioceptive
      sense, rather than through visual distortion. We used a coordinated movement task
      that required participants to release thumb and index finger at a specific elbow
      angle during passive elbow extension. Participants could not see their arm, but
      were shown a cursor representing the forearm on a video screen. In the
      proprioceptive group, a sensory conflict was introduced by vibrating the biceps
      brachii muscle, introducing a discrepancy of approximately 7.5 degrees between
      the proprioceptively perceived and visually perceived elbow angle. In the visual
      group, a conflict of similar magnitude was obtained by introducing a gain of 7.5
      degrees to the cursor with respect to forearm position. Adaptation was assessed
      by the presence of plastic changes in release elbow angles following a period of
      exposure to the sensory conflict (i.e., aftereffects). Both groups showed high
      accuracy during exposure despite the sensory conflicts. More importantly, the
      visual group presented large and persistent aftereffects, while the
      proprioceptive group presented none. We suggest that the proprioceptive group's
      lack of adaptation was due to the artificial muscle spindle activity resulting
      from vibration, which prevented visual and proprioceptive signals to be merged
      into a common frame of reference.

PMID- 16957885
TI  - Dynamics of the horizontal vestibuloocular reflex after unilateral
      labyrinthectomy: response to high frequency, high acceleration, and high velocity
      rotations.
AB  - Loss of vestibular information from one labyrinth results in a marked asymmetry
      in the horizontal vestibuloocular reflex (VOR). The results of prior studies
      suggest that long-term deficits in VOR are more severe in response to rapid
      impulses than to sinusoidal head movements. The goal of the present study was to
      investigate the VOR following unilateral labyrinthectomy in response to different
      stimuli covering the full range of physiologically relevant head movements in
      macaque monkeys. The VOR was studied 1-39 days post-lesion using transient head
      perturbations (up to 12,000 degrees/s(2)), rapid rotations (up to 500 degrees/s),
      and sinusoidal rotations (up to 15 Hz). In response to rotations with high
      acceleration or velocity, both contra- and ipsilesional gains remained subnormal.
      VOR gains decreased as a function of increasing stimulus acceleration or
      velocity, reaching minimal values of 0.7-0.8 and 0.3-0.4 for contra and
      ipsilesional rotations, respectively. For sinusoidal rotations with low
      frequencies and velocities, responses to contralesional stimulation recovered
      within approximately 4 days. With increasing velocities and frequencies of
      rotation, however, the gains of contra- and ipsilesional responses remained
      subnormal. For each of the most challenging stimuli tested (i.e., 12,000
      degrees/s(2 )transient head perturbations, 500 degrees/s fast whole-body
      rotations and 15 Hz stimulation) no significant compensation was observed in
      contra- or ipsilesional responses over time. Moreover, we found that gain of the
      cervico-ocular reflex (COR) remained negligible following unilateral loss
      indicating that neck reflexes did not contribute to the observed compensation.
      VOR responses elicited by both sinusoidal and transient rotations following
      unilateral labyrinthectomy could be described by the same mathematical model. We
      conclude that the compensated VOR has comparable response dynamics for impulses
      and sinusoidal head movements.

PMID- 16957886
TI  - Lack of influence of body mass index on efficacy and tolerance of acemetacin in
      short-term treatment of musculoskeletal diseases.
AB  - Dose adjustments of NSAIDs according to body weight may be reasonable for an
      optimal efficacy/tolerance profile in the therapy of musculoskeletal disorders,
      but are unusual in adults. In this post hoc analysis of a prospective, one-arm
      clinical study of a short-term treatment with acemetacin, a total of 406 patients
      with pain because of various musculoskeletal diseases with or without joint
      inflammation was evaluated for the influence of body mass index (BMI) on the
      reduction of pain at rest, pain at movement and for mobility restriction between
      visits one and three (primary outcome parameters). No association was found
      between BMI and the efficacy of acemetacin regarding the primary outcome
      parameters and no influence of BMI on the occurrence of adverse events was
      observed. Dose adjustment of acemetacin according to BMI thus appears not
      necessary in a short-term treatment of musculoskeletal disorders, but prospective
      controlled trials are needed to confirm these results.

PMID- 16957887
TI  - Characterization and outcome of uveitis in 350 patients with
      spondyloarthropathies.
AB  - This retrospective study analyzed 350 patients with the diagnosis of
      spondyloarthropathies (SPA) (207 with ankylosing spondylitis (AS), 80 with
      undifferentiated spondyloarthropathies (USPA) and 63 with psoriatic arthritis
      (PsA)) attended at a tertiary referral hospital for a minimum period of 5 years.
      All the patients presented complete clinical (axial and peripheral involvement,
      heel enthesopathies, extra-articular manifestations) and radiologic (sacroiliac,
      lumbar, dorsal and cervical spine) evaluation. HLA-B27 and respective alleles
      were searched. These data were compared with the occurrence of uveitis during the
      follow-up of the SPA patients. Thirty AS patients (14.5%) presented 55 episodes
      of acute anterior uveitis; there was statistical association between uveitis and
      juvenile-onset AS (P = 0.0094) and achillean (P = 0.0003) and plantar (P =
      0.0067) enthesopathies; one AS patient presented a single episode of posterior
      uveitis, associated to tuberculosis. Seven USPA patients (8.8%) presented 13
      episodes of acute anterior uveitis; it was not observed statistical association
      with any variable; one patient presented a single episode of posterior uveitis,
      associated to toxoplasmosis. Five HLA-B27 positive PsA patients (8%) presented 13
      episodes of acute anterior uveitis. All the 26 positive HLA-B27 SPA patients with
      anterior uveitis tested for the HLA-B27 alleles were HLA-B*2705. No patient
      presented ophthalmologic severe sequelae of the anterior uveitis. Concluding,
      anterior uveitis was associated to the juvenile onset of the disease and to the
      enthesophatic involvement of the lower limbs in AS patients. The HLA-B*2705
      allele was predominant in the anterior uveitis patients, whilst posterior uveitis
      was rare and associated to infectious disease.

PMID- 16957888
TI  - Successful treatment of acquired amegakaryocytic thrombocytopenia with
      cyclosporine in adult onset Still's disease.
AB  - Acquired amegakaryocytic thrombocytopenia (AAT) is a rare disorder, characterized
      by severe thrombocytopenia and selective, marked decrease or absence of
      megakaryocytes in the bone marrow. We describe a 29-year-old female with adult
      onset Still's disease preceding a diagnosis of AAT and autoimmune hemolytic
      anemia, which was successfully treated with cyclosporine. This is the first case
      of AAT in a patient with adult onset Still's disease.

PMID- 16957889
TI  - Course of damage to the hallux over 5 years after forefoot resection arthroplasty
      in rheumatoid arthritis patients.
AB  - A retrospective study of 34 feet from 20 consecutive patients with rheumatoid
      arthritis was performed to investigate the development of damage to the hallux
      over 5 years after forefoot resection arthroplasty. Radiographically we analysed
      changes in two valgus angles and the interphalangeal joint (IP) damage of the
      hallux. These parameters were measured preoperatively, 12 months postoperatively,
      and at the latest follow-up. Although the average HVA (between the first
      metatarsal and the proximal phalanx) significantly decreased from 38.7 degrees
      preoperatively to 8.66 degrees postoperatively, the angle increased to 23.0
      degrees during the first 12 months following surgery. Further deterioration of
      the angle at the last follow-up was not detected (25.3 degrees ; P=0.252). The
      average IPV (between the proximal phalanx and the distal phalanx) angle
      significantly increased from 6.65 degrees preoperatively to 12.1 degrees 12
      months postoperatively and thereafter slightly increased to 13.3 degrees at the
      latest follow-up. The average of the Sharp/van der Heijde score of the IP joint
      significantly increased from 5.71 preoperatively to 8.58 12 months
      postoperatively and thereafter slightly increased to 9.65 at the latest follow
      up. The deterioration and destruction process of the hallux after resection
      arthroplasty occurred soon after surgery, and the progression of the deformity
      was temporary.

PMID- 16957891
TI  - Neuroendocrine cell hyperplasia of infancy (NEHI).

PMID- 16957890
TI  - EPO: renoprotection beyond anemia correction.
AB  - Until recently the major physiological function of erythropoietin (EPO) was
      thought to be the induction of erythropoiesis. However, a growing body of
      evidence indicates that EPO has tissue-protective properties and prevents
      ischemia induced tissue damage in several organs including the kidney. A pivotal
      intracellular pathway mediating the beneficial effects of EPO is the activation
      of Akt, i.e. serine/threonine protein kinase B. As a result, Akt phosphorylates
      the proapoptotic factor Bad, which in turn causes inhibition of programmed cell
      death (apoptosis). In the present article we review data on the non-hematological
      effects of recombinant human EPO (rHuEPO) in different experimental settings of
      acute and chronic kidney injury, and discuss clinical renoprotective strategies
      with rHuEPO or analogues substances that are not related to anemia correction.

PMID- 16957892
TI  - Heat-inducible production of beta-glucuronidase in tobacco hairy root cultures.
AB  - The production of beta-glucuronidase (GUS) driven by the Arabidopsis small heat
      shock protein 18.2 promoter in liquid cultures of transgenic tobacco (Nicotiana
      tabacum) hairy roots is reported. Clone GD-3, showing high GUS heat induction and
      a moderate growth rate, was selected from 436 clones for study. Treatment of GD-3
      with heat shock at 36-42 degrees C for 2 h then recovery at 27 degrees C resulted
      in an increase in GUS specific activity, while higher heat-shock temperatures led
      to a decline. These results were in accordance with the change in esterase
      activity, a measure of tissue viability. Using 2 h of 42 degrees C heat shock and
      a recovery phase at 27 degrees C, GUS specific activity increased rapidly and
      reached a maximum of 267.6 nmol 4-methylumbelliferyl beta-D-glucuronic acid (MU)
      min-1 mg-1 protein at 24 h of recovery. When tissues were continuously heated at
      42 degrees C and tested without a recovery period, GUS mRNA was detectable at 2 h
      and peaked at 5 h, but GUS activity was not seen until 10 h and did not peak
      until 28 h; in addition, the maximum activity was lower than that seen after heat
      shock for only 30 min or 2 h, followed by recovery. This shows that recovery at
      normal temperature is crucial for the heat-inducible heterogeneous expression
      system of transgenic hairy roots. Multiple heat-shock treatments showed that this
      system was heat reinducible, although a gradual decline in GUS specific activity
      was seen in the second and third cycles.

PMID- 16957893
TI  - Extremolytes: Natural compounds from extremophiles for versatile applications.
AB  - Extremophilic microorganisms have adopted a variety of ingenious strategies for
      survival under high or low temperature, extreme pressure, and drastic salt
      concentrations. A novel application area for extremophiles is the use of
      "extremolytes," organic osmolytes from extremophilic microorganisms, to protect
      biological macromolecules and cells from damage by external stresses. In
      extremophiles, these low molecular weight compounds are accumulated in response
      to increased extracellular salt concentrations, but also as a response to other
      environmental changes, e.g., increased temperature. Extremolytes minimize the
      denaturation of biopolymers that usually occurs under conditions of water stress
      and are compatible with the intracellular machinery at high (>1 M)
      concentrations. The ectoines, as the first extremolytes that are produced in a
      large scale, have already found application as cell protectants in skin care and
      as protein-free stabilizers of proteins and cells in life sciences. In addition
      to ectoines, a range of extremolytes with heterogenous chemical structures like
      the polyol phosphates di-myoinositol-1,1'-phosphate, cyclic 2,3
      diphosphoglycerate, and alpha-diglycerol phosphate and the mannose derivatives
      mannosylglycerate (firoin) and mannosylglyceramide (firoin-A) were characterized
      and were shown to have protective properties toward proteins and cells. A range
      of new applications, all based on the adaptation to stress conditions conferred
      by extremolytes, is in development.

PMID- 16957894
TI  - Production of a chimeric enzyme tool associating the Trichoderma reesei swollenin
      with the Aspergillus niger feruloyl esterase A for release of ferulic acid.
AB  - The main goals of this work were to produce the fusion protein of the Trichoderma
      reesei swollenin I (SWOI) and Aspergillus niger feruloyl esterase A (FAEA) and to
      study the effect of the physical association of the fusion partners on the
      efficiency of the enzyme. The fusion protein was produced up to 25 mg l(-1) in
      the T. reesei strains Rut-C30 and CL847. In parallel, FAEA alone was produced for
      use as a control protein in application tests. Recombinant FAEA and SWOI-FAEA
      were purified to homogeneity and characterized. The biochemical and kinetic
      characteristics of the two recombinant proteins were found to be similar to those
      of native FAEA, except for the temperature stability and specific activity of the
      SWOI-FAEA. Finally, the SWOI-FAEA protein was tested for release of ferulic acid
      from wheat bran. A period of 24 h of enzymatic hydrolysis with the SWOI-FAEA
      improved the efficiency of ferulic acid release by 50% compared with the results
      obtained using the free FAEA and SWOI. Ferulic acid is used as an antioxidant and
      flavor precursor in the food and pharmaceutical industries. This is the first
      report of a potential application of the SWOI protein fused with an enzyme of
      industrial interest.

PMID- 16957895
TI  - Structure of microbial communities performing the simultaneous reduction of
      Fe(II)EDTA.NO2- and Fe(III)EDTA -.
AB  - BioDeNOx is a combined physicochemical and biological process for the removal of
      nitrogen oxides (NOx) from flue gas. In the present study, two anaerobic
      bioreactors performing BioDeNOx were run consecutively (RUN-1 and RUN-2) at a
      dilution rate of 0.01 h(-1) with Fe(II)EDTA.NO(2-) and Fe(III)EDTA(-) as electron
      acceptors and ethanol as electron donor. The measured protein concentration of
      the reactor biomass of both runs was 120 mg/l. Different molecular methods were
      used to determine the identity and abundance of the bacterial populations in both
      bioreactors. Bacillus azotoformans strain KT-1 was recognized as a key player in
      Fe(II)EDTA.NO(2-) reduction. PCR-denaturing gradient gel electrophoresis analysis
      of the reactor biomass showed a greater diversity in RUN-2 than in RUN-1.
      Enrichments of Fe(II)EDTA.NO(2-) and Fe(III)EDTA(-) reducers and activity assays
      were conducted using the biomass from RUN-2 as an inoculum. The results on
      substrate turnover, overall microbial diversity, and enrichments and finally
      activity assays confirmed that ethanol was used as electron donor for
      Fe(II)EDTA.NO(2-) reduction. In addition, the Fe(III)EDTA(-) reduction rate of
      the microbial community proved to be feasible enough to run the bioreactors,
      ruling out the chemical reduction of Fe(III)EDTA(-) with sulfide as was proposed
      by other researchers.

PMID- 16957896
TI  - Rapid intrinsic biodegradation of benzene, toluene, and xylenes at the boundary
      of a gasoline-contaminated plume under natural attenuation.
AB  - A groundwater plume contaminated with gasoline constituents [mainly benzene,
      toluene, and xylenes (BTX)] had been treated by pumping and aeration for
      approximately 10 years, and the treatment strategy was recently changed to
      monitored natural attenuation (MNA). To gain information on the feasibility of
      using MNA to control the spread of BTX, chemical and microbiological parameters
      in groundwater samples obtained inside and outside the contaminated plume were
      measured over the course of 73 weeks. The depletion of electron acceptors (i.e.,
      dissolved oxygen, nitrate, and sulfate) and increase of soluble iron were
      observed in the contaminated zone. Laboratory incubation tests revealed that
      groundwater obtained immediately outside the contaminated zone (the boundary
      zone) exhibited much higher potential for BTX degradation than those in the
      contaminated zone and in uncontaminated background zones. The boundary zone was a
      former contaminated area where BTX were no longer detected. Denaturing gradient
      gel electrophoresis (DGGE) analysis of polymerase chain reaction (PCR)-amplified
      bacterial 16S rRNA gene fragments revealed that DGGE profiles for groundwater
      samples obtained from the contaminated zone were clustered together and distinct
      from those from uncontaminated zones. In addition, unique bacterial rRNA types
      were observed in the boundary zone. These results indicate that the boundary zone
      in the contaminant plumes served as a natural barrier for preventing the BTX
      contamination from spreading out.

PMID- 16957897
TI  - Biosynthesis of poly(epsilon-L-lysine)s in two newly isolated strains of
      Streptomyces sp.
AB  - The biosynthesis of poly(epsilon-L-lysine) (epsilon-PL) in the two newly isolated
      strains of Streptomyces lydicus USE-11 (USE-11) and Streptomyces sp. USE-51 (USE
      51) was studied by a newly developed two-stage culture method of cell growth at
      pH 6.8 and epsilon-PL production at pH 4.5. USE-11 synthesized epsilon-PL
      consisting of about 28 residues at a high production level, whereas USE-51 did
      the polymer with 15 ones at a low level. The secreted epsilon-PLs in culture
      media were digested in a neutral pH range with a peptide hydrolase(s) produced by
      the epsilon-PL producers. The optimum production levels were presumed to be
      dependent upon the inherent epsilon-PL synthesis machinery of each producer. The
      production in USE-51 was sharply dependent upon cell density as was often
      observed in the production of antibiotics, whereas that in USE-11 was scarcely
      affected by the density. The SO(4)(2-) was found to be essential for the epsilon
      PL production in both strains. This might suggest the involvement of a thiol
      group in the polymerization reactions including the activation of L-lysine. This
      study indicates that USE-11 is a most suitable strain for the exploration of the
      epsilon-PL biosynthesis at the molecular level as well as for the technical
      applications.

PMID- 16957898
TI  - Surgical management to conjoined twins in Shanghai area.
AB  - Conjoined twins are very rare congenital malformation. The aim of this study was
      to summarize our experiences of surgical separation on seven sets of conjoined
      twins, and improve the treatment of conjoined twins in the future. A
      retrospective review of surgical separation included data of prenatal diagnosis,
      associated malformation, timing of separation, intra- and postoperative
      management, and follow-up of six sets of conjoined twins at Shanghai Xin-Hua
      Hospital from 1980 to 2005 and one set at Shanghai Children's Hospital in 2002.
      Surgical separation was performed on seven sets of conjoined twins; six sets of
      thoracopagus-omphalapagus (including four sets of xipho-omphalopagus) and one set
      of ischiopagus. All sets presented varying degrees of severity of congenital
      cardiac malformations. Four sets were diagnosed prenatally by ultrasonography.
      Two sets of conjoined twins (case 2 and case 3) required emergent separation
      within 7 days after birth; both members of case 2 died within 2 days post
      operation, one member of case 3 died during operation while the other member
      survived. Five sets had scheduled separation undertaken more than 30 days after
      birth. One member of a set (case 6B) died 13 days after operation due to severe
      congenital cardiovascular anomalies. All other members of conjoined twins
      survived. Case 6A had a severe defect of the anterior thoracic cage and
      prosthesis of titanium alloy scaffold filled with silicone rubber was used to
      repair the defects successfully. Following up from 1980 to 2005, one member of a
      set (case 1A) died 4 years after operation due to pneumonia. Contact was lost to
      the surviving member of case 3 (ischiopagus). Other survivors of the separations
      had normal development. (1) Timing of operation and separation plan should be
      given according to the circumstances and the nature of the organ shared in each
      individual set of twins. (2) Prosthesis of titanium alloy scaffolds filled with
      silicone rubber may become one of viable methods for repairing severe defects of
      the thoracic cage.

PMID- 16957899
TI  - Severe systemic vasculitis in a neonate.

PMID- 16957900
TI  - Multiple oxidative phosphorylation deficiencies in severe childhood multi-system
      disorders due to polymerase gamma (POLG1) mutations.
AB  - Failure to thrive, feeding difficulties, variable forms of infantile epilepsy or
      psychomotor developmental delay and hypotonia were the most frequent clinical
      disease presentations in eight children with combined oxidative phosphorylation
      enzyme complex deficiencies carrying mutations in the polymerase gamma (POLG1)
      gene. Five out of eight patients developed severe liver dysfunction during the
      course of the disease. Three of these patients fulfilled the disease criteria for
      Alpers syndrome. Most children showed deficiencies of respiratory chain enzyme
      complexes I and III, in combination with complex II, complex IV and/or PDHc in
      muscle, whereas in fibroblasts normal enzyme activities were measured. All
      children carried homozygous or compound heterozygous mutations in the POLG1 gene,
      including two novel mutations in association with mtDNA depletion. Conclusion We
      suggest performing POLG1 mutation analysis in children with combined oxidative
      phosphorylation deficiencies in muscle, even if the clinical picture is not
      Alpers syndrome.

PMID- 16957901
TI  - Impact of piperacillin resistance on the outcome of Pseudomonas ventilator
      associated pneumonia.
AB  - BACKGROUND: The impact of antibiotic resistance on the outcome of infections due
      to Gram-negative bacilli, especially Pseudomonas, remains highly controversial.
      STUDY OBJECTIVE, DESIGN, AND PATIENTS: We evaluated the impact of piperacillin
      resistance on the outcomes of Pseudomonas aeruginosa ventilator-associated
      pneumonia (VAP) for patients who had received appropriate empiric antibiotics
      before enrollment in the PNEUMA trial, a multicenter randomized study comparing 8
      vs 15 days of antibiotics. RESULTS: Despite similar characteristics at intensive
      care unit (ICU) admission, patients infected with piperacillin-resistant
      Pseudomonas strains were more acutely ill at VAP onset and had a higher 28-day
      mortality rate (37 vs 19%; P = 0.04) than those with piperacillin-susceptible
      Pseudomonas VAP. Factors associated with 28-day mortality retained by
      multivariable analysis were: age (OR: 1.07; 95% CI: 1.03-1.12); female gender
      (OR: 4.00; 95% CI: 1.41-11.11); severe underlying comorbidities (OR: 2.73; 95%
      CI: 1.02-7.33); and SOFA score (OR: 1.17; 95% CI: 1.03-1.32), but piperacillin
      resistance did not reach statistical significance (OR: 2.00; 95% CI: 0.72-5.61).
      The VAP recurrence rates, either superinfection or relapse, and durations of
      mechanical ventilation and ICU stay did not differ as a function of Pseudomonas
      resistance status. CONCLUSIONS: For patients with Pseudomonas VAP benefiting from
      appropriate empiric antibiotics, piperacillin resistance was associated with
      increased disease severity at VAP onset and higher 28-day crude mortality;
      however, after controlling for confounders, piperacillin-resistance was no longer
      significantly associated with 28-day mortality. The VAP recurrence rates and
      durations of ICU stay and mechanical ventilation did not differ for susceptible
      and resistant strains.

PMID- 16957902
TI  - Expanding our horizons beyond the intensive care unit: does mechanism of lung
      injury influence the quality of life in ARDS survivors?

PMID- 16957903
TI  - When (quality of) life is at stake and intensive care is needed: how much can we
      trust our proxies?

PMID- 16957904
TI  - Difference in reported pre-morbid health-related quality of life between ARDS
      survivors and their substitute decision makers.
AB  - CONTEXT: Substitute decision makers may consider the pre-morbid health status of
      their critically ill loved one when making treatment decisions on her/his behalf.
      OBJECTIVE: To compare estimates of pre-morbid health-related quality of life
      (HRQOL) obtained from survivors of the acute respiratory distress syndrome (ARDS)
      with those of their substitute decision makers using the Short Form 36 (SF-36).
      DESIGN: Prospective cohort study. SETTING: University-affiliated intensive care
      unit in Toronto, Canada. PATIENTS: A sample of 46 ARDS survivors and their
      substitute decision makers drawn from a previously described cohort.
      INTERVENTIONS: We measured agreement and differences between responses on the SF
      36 obtained from survivors (at 3 months after ICU discharge) and their substitute
      decision makers (at study entry). MEASUREMENTS AND RESULTS: Agreement was poor
      for all SF-36 components and differences reached significance in three domains.
      In multivariable analysis considering age; sex; Acute Physiology, Age, and
      Chronic Health Evaluation II score; and Lung Injury Score, only patient age was
      associated with the mean difference between estimates for the 'Mental Health'
      domain. On average, estimates of pre-morbid HRQOL obtained from substitute
      decision makers were lower than those obtained from survivors. CONCLUSION:
      Agreement between estimates of pre-morbid HRQOL provided by ARDS survivors and
      their substitute decision makers was poor. Compared with survivors, proxies
      tended to provide lower estimates of pre-morbid HRQOL. Substitute decision making
      for incapacitated patients is an imperfect process during which family members
      may underestimate their loved ones' own perception of pre-morbid health status.
      Alternatively, survivors of critical illness may overestimate pre-morbid HRQOL.

PMID- 16957905
TI  - Evaluation of the Binax NOW Streptococcus pneumoniae urinary antigen assay in
      intensive care patients hospitalized for pneumonia.
AB  - OBJECTIVE: To evaluate the diagnostic performance of Binax Now S. pneumoniae
      urinary antigen rapid immunochromatographic membrane test (ICT) for patients with
      suspicion of community-acquired pneumonia hospitalized in intensive care and to
      assess the impact of prior antibiotics on its diagnostic performance. DESIGN AND
      SETTING: Retrospective study in a medicosurgical ICU in a 700-bed general
      hospital. PATIENTS: Charts of patients with ICT performed (result blinded) were
      reviewed between May 2002 and July 2004. ICT has been performed in 140 of the
      1,006 patients hospitalized in the unit; two-thirds had received antibiotics
      prior to admission. MEASUREMENTS AND RESULTS: Diagnosis of pneumonia was made
      according to usual criteria. All patients had at least one microbiological test.
      Pneumonia diagnosis confirmed in 108 patients including 32 pneumococcal. ICT was
      positive in 23 of 32 patients with pneumococcal pneumonia, in 11 of 108 without,
      and in none of the 32 patients without pneumonia, resulting in sensitivity,
      specificity, and positive and negative predictive values of, respectively: 72%,
      90%, 68% and 92%. Positive likelihood ratios were comparable among patients with
      or without prior antibiotics (respectively 6 and 12 for 7 in the overall
      population). CONCLUSIONS: This first clinical evaluation of ICT in intensive care
      patients hospitalized for suspicion of community-acquired pneumonia, demonstrated
      performance in accordance with published data even in the case of prior
      antibiotics. Its clinical interest and impact on antibiotics policy remain to be
      refined.

PMID- 16957906
TI  - Genetic variation and the assessment of risk in septic patients.

PMID- 16957907
TI  - A systematic review of the quality of genetic association studies in human
      sepsis.
AB  - OBJECTIVE: Epidemiological studies demonstrate that inherited factors play a
      major role in the development and prognosis of sepsis. However, genetic
      association studies in sepsis have produced contradictory evidence of an effect
      from individual polymorphisms. Major methodological flaws have been reported in a
      number of genetic association studies in non-septic populations, relating to
      problems with experimental design, statistical analysis, study size, power and
      replication. We hypothesised that genetic association studies investigating
      sepsis suffer from similar problems, and that this explains the lack of
      consistent evidence for an effect from polymorphisms. DESIGN: A systematic review
      was conducted of published genetic association studies in sepsis from 1996-2005
      using a newly devised scoring system for study quality and rigour. A Bayesian
      statistical analysis was also carried out to assess the false-positive report
      probability of identified studies. MEASUREMENTS AND RESULTS: Study quality was
      assessed using a 10-point scoring system designed from published reporting
      guidelines. The majority of studies were of low to intermediate quality, with
      deficiencies in control group selection, genetic assay technique, study blinding,
      statistical interpretation, study replication, study size and power. Bayesian
      analysis indicated that many of the studies reporting a positive association
      between a genetic polymorphism and sepsis were likely to represent false-positive
      associations. CONCLUSIONS: The quality and size of genetic association studies in
      septic patients needs to improve if advances in identifying genetic effects in
      sepsis are to occur. Investigators should, as a minimum, follow recommended
      guidelines when designing studies.

PMID- 16957908
TI  - Malignant transformation in mature cystic teratoma of the ovary: report of five
      cases and review of the literature.
AB  - The incidence of malignant transformation in mature cystic teratoma (MCT) of the
      ovary is less than 2% as reported in gynaecological and pathological literature.
      Here we present a series of five patients, who developed malignant transformation
      in MCT of the ovary, over a 6-year period (1999-2004). The morphological and
      clinico-pathological features of malignant transformation in MCT of the ovary are
      discussed.

PMID- 16957909
TI  - Pregnancy followed by caesarean delivery in a patient with tracheostomy and
      gastrostomy after corrosive acid ingestion.
AB  - Corrosive acid ingestion in pregnancy is rare. We present a rare case of
      corrosive acid ingestion during pregnancy. The patient subsequently had tracheal
      stenosis and had to undergo a tracheostomy. Feeding gastrostomy was created for
      nutritional support of both mother and fetus. The patient delivered at term by an
      elective caesarean section.

PMID- 16957910
TI  - Successful pregnancy achieved by assisted reproductive techniques in a woman with
      severe congenital bicuspid aortic valve stenosis.
AB  - OBJECTIVES: To report a twin pregnancy achieved by assisted reproductive
      techniques in a woman with severe congenital bicuspid aortic valve stenosis.
      METHODS: Intracytoplasmic sperm injection and embryo transfer was performed in a
      38-year-old woman with a complaint of infertility for 8 years due to male factor
      and who previously had the diagnosis of severe congenital bicuspid aortic
      stenosis. Clinical and echocardiography follow-up during pregnancy was done.
      RESULTS: The woman had severe congenital aortic stenosis with a valve area of 0.4
      cm(2) and a peak gradient of 57 mmHg. In the first trial, twin pregnancy was
      achieved. She had an uneventful course of pregnancy in terms of cardiac
      functions. She underwent caesarean section at 36 weeks of gestation and had a
      healthy female and a male newborns. CONCLUSIONS: A woman with a severe congenital
      bicuspid aortic valve may get pregnant and deliver healthy newborns with
      intensive prenatal care and follow-up. The severe congenital bicuspid aortic
      valve stenosis may not be considered an absolute contraindication for assisted
      reproductive techniques and pregnancy.

PMID- 16957911
TI  - Single-day therapy: an expert opinion on a recent development for the episodic
      treatment of recurrent genital herpes.
AB  - One common method for treating recurrent genital herpes outbreaks is 3-5 day
      episodic therapy with nucleoside analogues. However, since maximum viral
      replication occurs within 24 h after the onset of symptoms, short-term patient
      initiated episodic therapy started at prodromal onset or at the first appearance
      of lesions in patients without a prodrome may represent an important option. In a
      recent randomized trial, single-day famciclovir treatment decreased lesion
      healing time and the duration of pain and other symptoms by approximately 2 days
      compared to placebo, and prevented progression to a full outbreak in almost one
      in four patients. Because single-day treatment is more convenient than
      traditional therapies, it may lead to improved patient compliance and better
      overall management of recurrent genital herpes outbreaks.

PMID- 16957912
TI  - An early diagnosis and successful local medical treatment of a rudimentary
      uterine horn pregnancy: a case report.

PMID- 16957913
TI  - Silent rupture of unscarred uterus: an unusual presentation at second trimester
      abortion.
AB  - Rupture of unscarred uterus during the second trimester is rare. A case of
      ruptured uterus in a multiparous woman is presented. To our knowledge, this might
      be the first reported case in the English literature of uterine rupture during
      second trimester termination of pregnancy using ethacridine lactate. This case is
      also rare as uterine rupture is presented with an insidious course rather than
      acute, thus delaying the diagnosis.

PMID- 16957914
TI  - Determination of ruscogenin in crude Chinese medicines and biological samples by
      immunoassay.
AB  - Ruscogenin is a major bioactive steroidal aglycone found in the Chinese medicine,
      Ophiopogon japonicus. We have developed a quantitative determination of
      ruscogenin with an indirect enzyme-linked immunosorbent (ELISA) assay using
      polyclonal antibodies against ruscogenin conjugated with bovine serum albumin.
      This assay was highly sensitive, and it had considerably less cross-reactivity to
      diosgenin and sarsasapogenin, but high cross-reactivity to ruscogenin glycosides.
      The assay was successfully used for the measurement of ruscogenin concentrations
      in crude Chinese medicines and in biological samples from a pharmacokinetics
      study of ruscogenin.

PMID- 16957915
TI  - Determination of haloperidol and reduced haloperidol in human serum by liquid
      chromatography after fluorescence labeling based on the Suzuki coupling reaction.
AB  - A simultaneous method for the determination of haloperidol (HP) and its
      metabolite, reduced haloperidol (RHP), in human serum was developed by means of
      high-performance liquid chromatography (HPLC) with fluorescence detection. Suzuki
      coupling reaction with a fluorescent arylboronic acid, 4-(4,5-diphenyl-1H
      imidazol-2-yl)phenylboronic acid (DPA), was employed to convert HP and RHP into
      highly fluorescent compounds. HP and RHP were extracted from human serum by
      liquid-liquid extraction with a mixture of n-hexane and isoamyl alcohol (99:1,
      v/v) and subsequently labeled by reaction with DPA. Separation of DPA derivatives
      of HP and RHP was performed on a silica column with a mixture of acetonitrile and
      H(2)O (90:10, v/v) containing triethylamine and acetic acid as a mobile phase.
      The proposed method allowed sensitive detection of HP and RHP in human serum with
      a detection limit (at a signal to noise ratio of 3) of 0.22 and 0.20 ng/mL,
      respectively. The applicability of the method for therapeutic drug monitoring
      (TDM) was demonstrated by analyzing human serum samples from schizophrenic
      patients receiving HP.

PMID- 16957916
TI  - Environmental analysis of single cells.

PMID- 16957917
TI  - Theoretical study of the reduction of nitric oxide in an A-type flavoprotein.
AB  - The mechanism for the reduction of nitric oxide to nitrous oxide and water in an
      A-type flavoprotein (FprA) in Moorella thermoacetica, which has been proposed to
      be a scavenging type of nitric oxide reductase, has been investigated using
      density functional theory (B3LYP). A dinitrosyl complex, [{FeNO}(7)](2), has
      previously been proposed to be a key intermediate in the NO reduction catalyzed
      by FprA. The electrons and protons involved in the reduction were suggested to
      "super-reduce" the dinitrosyl intermediate to [{FeNO}(8)](2) or the corresponding
      diprotonated form, [{FeNO(H)}(8)](2). In this type of mechanism the electron
      and/or proton transfers will be a part of the rate-determining step. In the
      present study, on the other hand, a reaction mechanism is suggested in which
      N(2)O can be formed before the protons and electrons enter the catalytic cycle.
      One of the irons in the diiron center is used to stabilize the formation of a
      hyponitrite dianion, instead of binding a second NO. Cleaving the N-O bond in the
      hyponitrite dianion intermediate is the rate-determining step in the proposed
      reaction mechanism. The barrier of 16.5 kcal mol(-1) is in good agreement with
      the barrier height of the experimental rate-determining step of 14.8 kcal mol(
      1). The energetics of some intermediates in the "super-reduction" mechanism and
      the mechanism proceeding via a hyponitrite dianion are compared, favoring the
      latter. It is also discussed how to experimentally discriminate between the two
      mechanisms.

PMID- 16957919
TI  - DFT study of new bipyrazole derivatives and their potential activity as corrosion
      inhibitors.
AB  - In the present work, a theoretical study of five bipyrazolic-type organic
      compounds, 4-{bis[(3,5-dimethyl-1H-pyrazolyl-1-yl)methyl]-amino}phenol (1), N1,N1
      bis[(3,5-dimethyl-1H-pyrazol-1-yl)methyl}]-N4,N4-dimethyl-1,4-benzenediamine (2),
      N,N-bis[(3,5-dimethyl-1H-pyrazol-1-yl)methyl]aniline (3), 4-[bis(3,5-dimethyl
      pyrazol-1-yl-methyl)-amino]butan-1-ol (4) and ethyl4-[bis(3,5-dimethyl-1H-pyrazol
      1-yl-methyl) aminobenzoate] (5), has been performed using density functional
      theory (DFT) at the B3LYP/6-31G(d) level in order to elucidate the different
      inhibition efficiencies and reactive sites of these compounds as corrosion
      inhibitors. The efficiencies of corrosion inhibitors and the global chemical
      reactivity relate to some parameters, such as EHOMO, ELUMO, gap energy (DeltaE)
      and other parameters, including electronegativity (chi), global hardness (eta)
      and the fraction of electrons transferred from the inhibitor molecule to the
      metallic atom (DeltaN). The calculated results are in agreement with the
      experimental data on the whole. In addition, the local reactivity has been
      analyzed through the Fukui function and condensed softness indices.

PMID- 16957918
TI  - EF-hand protein dynamics and evolution of calcium signal transduction: an NMR
      view.
AB  - Calcium signaling, one of the most widespread signaling mechanisms in cells, is
      generally carried out by EF-hand proteins, characterized by a helix-loop-helix
      motif paired in functional domains. EF-hand proteins may be viewed as molecular
      switches activated by calcium concentration transients. The EF-hand structural
      database has grown to a point where meaningful inferences on the functional
      conformational rearrangements upon calcium binding can be made by comparing a
      fair number of pairs of end points, i.e., the structures of the apo and calcium
      bound forms. More compact descriptors of the movement associated with calcium
      binding, in terms of principal component analysis of the six interhelical angles,
      have also become available. Dynamic information obtained by NMR, also with the
      aid of calcium substitution with paramagnetic lanthanides, is shedding light on
      the intrinsic amplitude of the conformational degrees of freedom sampled by the
      various members of the EF-hand superfamily, as well as on the time scales of the
      motions. Particularly, NMR of lanthanide derivatives helps in capturing long time
      scale motions. Both static and dynamic pictures reveal a large variety of
      behaviors. It is increasingly recognized that the EF-hand machinery has
      differentiated its behavior during evolution in several ways, e.g., by modifying
      one of the loops, by undergoing a further duplication after the initial motif
      duplication that originated the functional domain, or by acquiring the ability to
      dimerize.

PMID- 16957920
TI  - Topochemical models for the prediction of voltage-gated sodium channel binding
      activity of hydantoins and related non-hydantoins.
AB  - The relationship of Wiener's topochemical index-a distance based topochemical
      index, molecular connectivity topochemical index-an adjacency based topochemical
      index and eccentric connectivity topochemical index-an adjacency-cum-distance
      based topochemical index with sodium channel binding activity has been
      investigated. A dataset comprising 50 hydantoins and related non-hydantoins was
      selected. The dataset was divided equally into training and test sets. The values
      of the three topochemical indices for all the compounds present in both the
      training and test sets were computed using an in-house computer program. The
      resulting data was analyzed and suitable models were developed after
      identification of the active ranges in the training set. Subsequently, a
      biological activity was assigned to each compound involved in the training set
      using these models, which was then compared with the reported sodium channel
      binding activity. An accuracy of prediction of the order of >99% was observed
      using the proposed models. Cross-validation of these models using the test set
      revealed an exceptionally high accuracy of approximately 95%.

PMID- 16957921
TI  - A male gift to its partner? Cyanogenic glycosides in the spermatophore of
      longwing butterflies (Heliconius).
AB  - Males of several insect species transfer nuptial gifts to females during mating,
      typically in the form of a protein-rich spermatophore. In chemically defended
      species, males could potentially enhance such a gift with chemicals that help
      protect the female, her eggs, or both. This was shown for lepidopteran species
      that accumulate pyrrolizidine alkaloids. Most Heliconius butterflies are
      presumably protected from predators by virtue of de novo synthesized and/or
      sequestered cyanogenic glycosides. Males of Heliconius species are known to
      transfer nutritional gifts to the females but whether defensive chemicals could
      also be transferred is not known. To ascertain whether transfer of cyanogens
      occurs, we dissected freshly mated females from nine different Heliconius species
      and analyzed spermatophores for cyanogenic glycosides. We found cyanogens in the
      spermatophores of all nine species. This is the first time cyanogenic glycosides
      are reported in the spermatophores of arthropods. We discuss the implications of
      these findings for Heliconius biology and for other cyanogenic insects as well.
      We suggest that chemically defended species commonly lace their nuptial gifts
      with defensive chemicals to improve gift quality.

PMID- 16957922
TI  - Ubiquity of parasporin-1 producers in Bacillus thuringiensis natural populations
      of Japan.
AB  - Parasporin, a Bacillus thuringiensis parasporal protein, is unique in having a
      strong cytocidal activity preferential for human cancer cells. In this study, we
      characterized parasporin activities associated with three novel geographical
      isolates of B. thuringiensis. Parasporal inclusion proteins of the three isolates
      were highly toxic to human uterus cervix cancer cells (HeLa), but not to non
      cancer uterine smooth muscle cells (UtSMC). Inclusions of the isolates lacked
      insect toxicity and hemolytic activity against sheep erythrocytes. Ouchterlony
      immunodiffusion tests revealed that the proteins of the three isolates are
      immunologically closely related to parasporin-1 (Cry31A), but dissimilar to the
      three other existing parasporin groups. Our results provide evidence that the
      parasporin-1-producing organism is a common member in B. thuringiensis
      populations occurring in natural environments of Japan.

PMID- 16957923
TI  - Expression of alpha2-macroglobulin, neutrophil elastase, and interleukin-1alpha
      differs in early-stage and late-stage atherosclerotic lesions in the arteries of
      the circle of Willis.
AB  - Different types of atherosclerotic (AS) lesions can be distinguished
      histologically and represent different stages of AS plaque development. Late
      stage lesions more frequently develop complications such as plaque rupture and
      thrombosis with vessel occlusion than early AS lesions. To clarify whether
      protective, destructive, and inflammatory proteins are differentially expressed
      in early-stage and late-stage AS plaques we examined the proteinase inhibitor
      alpha(2)-macroglobulin (A2M), the neutrophil elastase (NE)-an enzyme degrading
      elastin and collagen fibers-and the proinflammatory protein interleukin-1alpha
      (IL-1alpha) in all types of AS plaques in the arteries of the circle of Willis
      from 78 human autopsy cases of both genders (61-91 years of age). Paraffin
      sections of AS plaques were immunostained with antibodies directed against A2M,
      NE and IL-1alpha. In initial AS lesions A2M was found, whereas NE and IL-1alpha
      were absent. NE and IL-1alpha became detectable as soon as a significant number
      of macrophages occurred within AS lesions. With increasing histopathological type
      of AS lesions, a marked increase of the area of the plaque exhibiting NE and IL
      1alpha was observed. The area which exhibits A2M in AS plaques, on the other
      hand, did not vary significantly between the different stages. Thus, our results
      indicate a disproportionately high increase of the destructive enzyme NE and the
      proinflammatory protein IL-1alpha in relation to A2M with the progression of the
      grade of AS lesions pointing to the transgression of the protective capacity of
      A2M by NE and IL-1alpha in late-stage plaques. Therefore, our findings support
      the hypothesis that NE-induced tissue damage in late-stage AS plaques contributes
      to the development of plaque rupture and subsequent thrombosis.

PMID- 16957924
TI  - Distribution of the cellular prion protein (PrPC) in brains of livestock and
      domesticated species.
AB  - In transmissible spongiform encephalopathies (TSEs) the prion protein (PrP) plays
      a central role in pathogenesis. The PrP gene (Prnp) has been described in a
      number of mammalian and avian species and its expression product, the cellular
      prion protein (PrP(C)), has been mapped in brains of different laboratory animals
      (rodent and non-human primates). However, mapping of PrP(C) expression in
      mammalian species suffering from natural (bovine and ovine) and experimental
      (swine) TSE or in species in which prion disease has never been reported (equine
      and canine) deserves further attention. Thus, localising the cellular prion
      protein (PrP(C)) distribution in brain may be noteworthy for the understanding of
      prion disease pathogenesis since lesions seem to be restricted to particular
      brain areas. In the present work, we analysed the distribution of PrP(C)
      expression among several brain structures of the above species. Our results
      suggest that the expression of PrP(C), within the same species, differs depending
      on the brain structure studied, but no essential differences between the PrP(C)
      distribution patterns among the studied species could be established. Positive
      immunoreaction was found mainly in the neuropil and to a lesser extent in
      neuronal bodies which occasionally appeared strongly stained in discrete regions.
      Overall, the expression of PrP(C) in the brain was significantly higher in grey
      matter areas than in white matter, where accumulation of PrP(Sc) is first
      observed in prion diseases. Therefore, other factors besides the level of
      expression of cellular PrP may account for the pathogenesis of TSEs.

PMID- 16957925
TI  - alpha-Synuclein is colocalized with 14-3-3 and synphilin-1 in A53T transgenic
      mice.
AB  - alpha-Synuclein is a major constituent of Lewy bodies, the neuropathological
      hallmark of Parkinson's disease (PD). Three types of alpha-synuclein mutations,
      A53T, A30P, and E46K, have been reported in familial PD. Wild-type alpha
      synuclein accumulates at high concentrations in Lewy bodies, and this process is
      accelerated with mutated A53T alpha-synuclein. The accumulation of alpha
      synuclein is thought to be toxic, and causes neuronal death when alpha-synuclein
      aggregates into protofibrils and fibrils. Lewy bodies contain not only alpha
      synuclein, but also other proteins including 14-3-3 proteins and synphilin-1. 14
      3-3 Proteins exist mainly as dimers and are related to intracellular signal
      transduction pathways. Synphilin-1 is known to interact with alpha-synuclein,
      promoting the formation of cytoplasmic inclusions like Lewy bodies in vitro. To
      investigate the colocalization of alpha-synuclein, synphilin-1, and 14-3-3
      proteins, we performed immunohistochemical studies on alpha-synuclein, 14-3-3
      proteins, and synphilin-1 in the brain and spinal cord of A53T transgenic mice.
      In homozygous mouse brains, alpha-synuclein immunoreactivity was observed in the
      neuronal somata and processes in the medial part of the brainstem, deep
      cerebellar nuclei, and spinal cord. The distribution of 14-3-3 proteins and
      synphilin-1 immunoreactivity was similar to that of alpha-synuclein in the
      homozygous mice. Double immunofluorescent staining showed that alpha-synuclein
      and synphilin-1 or 14-3-3 proteins were colocalized in the pons and spinal cord.
      These results indicate that the accumulation of mutant alpha-synuclein occurs in
      association with 14-3-3 proteins and synphilin-1, and may cause the sequestration
      of important proteins including 14-3-3 proteins and synphilin-1. The
      sequestration and subsequent decrease in 14-3-3 proteins and synphilin-1 levels
      may account for neuronal cell death.

PMID- 16957926
TI  - MM2-thalamic-type sporadic Creutzfeldt-Jakob disease with widespread neocortical
      pathology.
AB  - We report an autopsy case of MM2-thalamic-type sporadic Creutzfeldt-Jakob disease
      (sCJD) with widespread cerebral neocortical pathology. Initial symptoms were
      progressive insomnia and mental disturbance. Magnetic resonance imaging revealed
      no high-signal intensity lesions on diffusion-weighted images and later showed
      gradually progressive cerebral atrophy. Periodic synchronous discharges and
      myoclonus were not observed. Upon neuropathologic examination, widespread
      cerebral neocortical involvement with fine vacuole-type spongiform change was
      observed. Severe degeneration with almost complete neuronal loss, tissue
      rarefaction, numerous fat-laden macrophages and hypertrophic astrocytosis of the
      medial thalamic nucleus was evident. The inferior olivary nucleus showed severe
      involvement with neuronal loss and hypertrophic astrocytosis. In the cerebellar
      cortex, moderate depletion of Purkinje neurons was evident, with no spongiform
      change in the molecular layer and no neuronal loss in the granule cell layer.
      Immunohistochemistry for prion protein (PrP) revealed widespread synaptic-type
      deposits with some primitive plaque-type deposits in the cerebral neocortex,
      basal ganglia and cerebellar cortex. PrP deposition was also observed in the
      brainstem, particularly the tegmentum, substantia nigra and pontine nucleus, and
      spinal cord, particularly the posterior horn. In the medial thalamus and inferior
      olivary nucleus, PrP deposition was sparse. Analysis of the PrP gene showed no
      mutation but did show methionine homozygosity at polymorphic codon 129. Western
      blot analysis of protease-resistant PrP indicated the presence of type 2 PrP. We
      believe that this patient suffered from MM2-thalamic-type sCJD (sporadic fatal
      insomnia) with widespread cerebral neocortical pathology due to prolonged disease
      duration. The present case showed different patterns of spongiform degeneration
      and PrP deposition in the cerebral neocortex than those in previously reported
      MM2-thalamic-type sCJD cases.

PMID- 16957927
TI  - Altered distributions of nucleocytoplasmic transport-related proteins in the
      spinal cord of a mouse model of amyotrophic lateral sclerosis.
AB  - Recent investigations have indicated that the nucleocytoplasmic transport system
      is essential for maintaining cell viability and cellular functions and that its
      dysfunction could lead to certain disorders. To investigate the involvement of
      this system in the pathomechanisms of amyotrophic lateral sclerosis (ALS), we
      examined the immunohistochemical localization of proteins associated with
      nucleocytoplasmic transport in the lumbar spinal cord in a mutant SOD1 (G93A)
      transgenic mouse model of ALS. This model is widely used for ALS research, and
      the mutant mice are known to exhibit neuronal loss and Lewy body-like hyaline
      inclusions (LBHIs) in the anterior horns, similar to the pathology seen in
      familial ALS patients associated with an SOD1 mutation and in several other
      transgenic rodent models. Using antibodies against the importin beta family of
      proteins, the major carrier proteins of nucleocytoplasmic transport, and those
      against their adapter protein, importin alpha, we found that the
      immunoreactivities were decreased within the nuclei and increased within the
      cytoplasm of a subset of the surviving anterior horn cells of the transgenic
      mice. In addition, LBHIs were invariably reactive toward these antibodies.
      Furthermore, the immunoreactivities for histone H1 and beta-catenin,
      representative cargo proteins transported by importin beta-dependent and beta
      independent nucleocytoplasmic transport pathways, respectively, showed
      distributions similar to those for importin beta family and importin alpha
      proteins. The altered distributions of these proteins were not associated with
      caspase-3 expression, suggesting that the findings are unlikely to be a
      manifestation of apoptotic processes. Chronological quantitative analysis of
      importin beta-immunostained sections from the transgenic mice revealed a
      statistically significant progressive decrease in the proportion of the anterior
      horn cells exhibiting a more intense reactivity for these proteins in the nucleus
      than in the cytoplasm. To the contrary, we found that the anterior horn cells
      with the immunoreactivity in their cytoplasm, being more pronounced than that in
      their nucleus, were significantly increased in number along with the disease
      progression. This is the first report investigating nucleocytoplasmic transport
      in the ALS model mouse, and our present results imply that its dysfunction could
      be involved in the pathomechanisms underlying ALS.

PMID- 16957928
TI  - Unusual malignant glioneuronal tumors of the cerebrum of adults: a
      clinicopathologic study of three cases.
AB  - Malignant glioneuronal tumors of the brain are rare and poorly characterized.
      Herein, we report the clinicopathologic features of three examples with unusual
      morphologies including both glial and neuronal differentiation. Hematoxylin and
      eosin-stained slides were reviewed in all cases. Immunohistochemical stains were
      performed on formalin-fixed, paraffin-embedded sections. Transmission electron
      microscopy (EM) was performed on both formalin-fixed (n=1) and paraffin embedded
      tissue (n=2). The immunogold technique for localization of GFAP was also
      performed. Two patients were male and one was female, age 66, 84, and 34 years,
      respectively. Radiologic studies demonstrated hyperdensity on CT (n=3),
      multicentricity (n=2), and a cortical based solid component with a cystic
      extension into underlying white matter (n=2). At surgery, all three tumors were
      superficial and relatively circumscribed. Histologically, they were composed of
      large epithelioid cells (n=3), spindle cells (n=1), and poorly differentiated
      smaller cells with high nuclear/cytoplasmic ratios (n=1). Brisk mitotic activity
      and coagulative non-palisading necrosis were present in all cases. The tumors
      were immunopositive for GFAP (n=3), S-100 (n=3), synaptophysin (n=3),
      chromogranin (n=3), Neu-N (n=2), and neurofilament protein (n=2). Stains for EMA
      were negative. EM demonstrated convincing neurosecretory granules in one case,
      some in filament-containing cells immunogold labeled for GFAP. Two patients
      expired 3-5 weeks after surgery. True malignant neoplasms with glial and neuronal
      differentiation do occur in the central nervous system of adults and may pursue a
      highly aggressive course. The use of minimal diagnostic criteria, e.g.,
      immunoreactivity for a single antigen like neurofilament protein, may not be
      sufficient and should be discouraged.

PMID- 16957929
TI  - Chronic circumferential periostitis of proximal phalanges related to tight
      fitting rings.
AB  - We present three cases of chronic erosion injuries to the phalanges seen at our
      institution. We review the literature regarding this uncommon injury and discuss
      the clinical scenarios in which these injuries may occur, the radiographic
      findings, treatment options, and outcomes.

PMID- 16957930
TI  - The synergistic effect of dimethylamino benzoylphenylurea (NSC #639829) and X
      irradiation on human lung carcinoma cell lines.
AB  - PURPOSE: The present study was designed to investigate the ability of N-[4-(5
      bromo-2-pyrimidyloxy)-3-methylphenyl]-(dimemethylamino)-benzoylphenylurea
      (dimemethylamino benzoylphenylurea; BPU) to sensitize cells to radiation and to
      examine the relationship between phenotype versus survival, DNA damage,
      apoptosis, or cell cycle progression in non-small cell lung cancer (NSCLC) cell
      lines. METHODS: Asynchronous cultures of three NSCLC (phenotype) lines, A549
      (adenocarcinoma), NCI-H226 (squamous) and NCI-H596 (adenosquamous) were used.
      Cells were treated for 24 h with BPU at various concentrations (0-10 microM) to
      obtain drug doses for inhibiting cell survival by approximately 50% (IC50). Cells
      were X-irradiated without BPU or after 24 h BPU treatment at IC50. Radiation
      doses ranged from 0 to10 Gy. Cell survival was determined by a colony-forming
      ability assay. The effect of BPU on the cell cycle distribution and induction of
      apoptosis were measured by flow cytometry-based assays. The effect of BPU on
      radiation-induced DNA damage and repair was analyzed according to nuclear
      gammaH2AX immunofluorescence of cells exposed to X-rays alone or after BPU. Anti
      gammaH2AX antibody staining, a surrogate determinant of double stranded DNA
      breaks, was measured using flow cytometry. RESULTS: BPU (1.5 microM) for 24 h
      produced approximately 50% cell survival. BPU and X-irradiation were synergistic
      in the three cell lines at survival levels of 20-50%. Flow cytometry analysis of
      replicate experiments with BPU (1.5 microM for 24 h) showed that BPU blocked cell
      progression at S and/or G2/M. The incidence of apoptosis in BPU-treated versus
      control cells ranged from approximately 0.3 to approximately 8%. Twenty-four hour
      after X-irradiation cells pre-treated with BPU and X-irradiated after drug
      exposure showed gammaH2AX levels approximately two times higher than did the
      cells exposed to X-rays only. CONCLUSIONS: The study identified BPU as a novel
      radiation sensitizer. The analysis of phosphorylated histone H2AX as a surrogate
      marker of DNA double strand breaks suggested a positive association between
      radiosensitization and the inhibition of X-irradiation-induced DNA damage repair
      by BPU.

PMID- 16957931
TI  - Characterization of two phase I metabolites of bendamustine in human liver
      microsomes and in cancer patients treated with bendamustine hydrochloride.
AB  - PURPOSE: The metabolism of bendamustine (BM) hydrochloride, a bifunctional
      alkylator containing a heterocyclic ring, was investigated in vitro and in vivo
      for identification of cytochromes P450 (CYP) involved in the formation of two
      phase I metabolites, structural confirmation of these previously unidentified
      metabolites and assessment of their cytotoxic effect in relation to the parent
      compound. METHODS: Potential metabolites of BM were synthesized and structurally
      characterized by nuclear magnetic resonance (NMR) and liquid chromatography-mass
      spectrometry (LC-MS) analysis. In vitro metabolism of BM hydrochloride in human
      hepatic microsomes was conducted to identify the CYP450 isoenzymes involved in
      the oxidative metabolism of BM. Samples from cancer patients after treatment with
      BM hydrochloride and microsomal preparations were analyzed by LC-MS and HPLC with
      fluorescence detection. The cytotoxic effect of the metabolites was analyzed in
      several lymphoma cell lines and peripheral blood lymphocytes and compared with
      that of the parent compound using an MTT assay. RESULTS: LC-MS as well as HPLC
      with fluorescence detection revealed hydroxylation of the methylene carbon at the
      C-4 position of the butanoic acid side chain and N-demethylation of the
      benzimidazole skeleton as the main metabolic pathways in human liver microsomes.
      Isoform-specific chemical inhibitors and correlation analysis pointed to CYP1A2
      as the prominent enzyme in BM oxidation. The rate of formation for both
      metabolites correlated (r=0.931 and 0.933) with the activity of CYP1A2 and there
      were no other notable correlations with any of the other CYPs. In addition, both
      metabolites were identified in plasma, urine, and bile samples from cancer
      patients under BM hydrochloride therapy as shown by comparison with chromatograms
      obtained from the authentic reference standards. Cytotoxic activity observed for
      gamma-hydroxy BM was approximately equivalent to that obtained for the parental
      compound BM. N-demethyl BM displays five to tenfold less cytotoxic activity than
      BM. CONCLUSION: The results indicate that CYP1A2-catalyzed N-dealkylation and
      gamma hydroxylation are the major routes for BM phase I metabolism producing two
      metabolites less or similarly toxic than the parent compound. In contrast to the
      metabolic pathways of the structurally related chlorambucil, no beta-oxidation of
      the butanoic acid side chain leading to enhanced toxicity was detected for BM.

PMID- 16957932
TI  - The range of optimal concentration and mechanisms of paclitaxel in radio
      enhancement in gastrointestinal cancer cell lines.
AB  - AIM: This study was performed to investigate the range of optimal concentration
      and mechanisms of paclitaxel (PXL) radio-enhancement in gastrointestinal cancer
      cell lines HT29 and MKN45. METHODS: Cell growth inhibition by PXL pretreatment at
      various concentrations (0-10 microM) followed by irradiation was investigated
      using a modified MTT assay. To investigate the mechanisms of the observed radio
      enhancement, flow cytometry was conducted to define the cell cycle distributions.
      Furthermore, the alterations in expression of a DNA repair molecule [excision
      repair cross-complementation group1 (ERCC1)] and an angiogenesis factor [vascular
      endothelial growth factor (VEGF)] induced by PXL were investigated. RESULTS:
      Cytotoxic concentrations of PXL (0.1-10 microM) that cause accumulation of cells
      in the G2/M phase have strong radio-enhancing effects and inhibit total cell
      growth. The maximal non-cytotoxic concentration of PXL (0.01 microM) also had a
      radio-enhancing effect. The expression of the genes of ERCC1 and VEGF induced by
      radiation was suppressed by PXL pretreatment. The protein secretion of VEGF
      induced by radiation was suppressed at cytotoxic doses of PXL, and the induced
      protein secretion of ERCC1 was also suppressed even at maximal non-cytotoxic
      doses of PXL. CONCLUSION: The range of optimal concentration for PXL pretreatment
      was 0.01-0.1 microM in these cells. Two major mechanisms of radio-enhancement are
      suggested: (1) PXL induces G2/M arrest leading to increased DNA damage after
      radiation, which results in mitotic death, and (2) PXL suppresses the expression
      of radiation-induced DNA repair molecules and angiogenesis factors, resulting in
      inhibition of cell growth and cell death.

PMID- 16957933
TI  - Para-testicular cellular angiofibroma: a rare tumour in a male renal transplant
      patient.
AB  - Cellular angiofibroma is a rare, benign, mesenchymal neoplasm that should be
      distinguished from other more aggressive mesenchymal lesions. A 32-year-old male
      presented with a painless para-testicular mass. Pathological examination showed
      features characteristic of cellular angiofibroma. He had a history of renal
      transplantation and was on immunosuppressive drugs. The pathogenesis of cellular
      angiofibroma is largely undetermined. The role of immunosuppressive therapy in
      the genesis of this tumour awaits further analysis.

PMID- 16957934
TI  - Tissue microarray profiling of primary and xenotransplanted synovial sarcomas
      demonstrates the immunophenotypic similarities existing between SYT-SSX fusion
      gene confirmed, biphasic, and monophasic fibrous variants.
AB  - This paper discusses the diversity of synovial sarcomas (SSs) [biphasic (BSS),
      monophasic fibrous (MFSS), and poorly differentiated (PDSS)] and tissue
      microarray (TMA) evaluation of the immunophenotypic and histological progression
      of SSs in nude mice using three TMAs comprising 11 primary SSs (8 MFSSs, 2 BSSs,
      and 1 PDSS) and their xenografts. BSS and MFSS progressively transformed to a
      similar undifferentiated phenotype with loss of glandular component in the
      xenografts. Epidermal growth factor receptor and SALL2 were expressed in primary
      tumors and xenografts. Enhanced bcl-2 and bax expression were noted in
      xenografts. Ki-67 overexpression in xenografts correlated with high mitotic
      index. Epithelial membrane antigen (EMA) and cytokeratin AE1/AE3 were detected in
      all original and xenografted SSs. Hierarchical clustering differentiated original
      MFSS and BSS, but their xenografts clustered together due to similar
      immunoexpression profile. Our study demonstrates definite phenotypic variability
      of BSS and MFSS in the xenografts. Differences in immunoexpression for various
      markers existed between primary tumor and xenografts but not between subtypes.
      Hierarchical clustering grouped TMA immunostaining data and confirmed
      immunophenotypic variability; however, it failed to reveal any immunophenotypic
      differences between SYT-SSX1 and SYT-SSX2 type tumors. Nonetheless, reverse
      transcriptase-polymerase chain reaction detected SYT-SSX transcripts in all
      primary SSs and their xenografts, thereby demonstrating their genetic stability.

PMID- 16957935
TI  - Increased numbers of osteoclasts expressing cysteine proteinase cathepsin K in
      patients with infected osteoradionecrosis and bisphosphonate-associated
      osteonecrosis--a paradoxical observation?
AB  - Erosion of the bone is a common problem in patients suffering from infected
      osteoradionecrosis (IORN) or bisphosphonate-associated osteonecrosis (BON).
      Besides inflammatory mechanisms and infectious agents, osteoclasts were recently
      suggested to be specifically involved in the osteolytic mechanisms. We therefore
      investigated the immunohistochemical labeling of the cysteine proteinase
      cathepsin K, which plays a central role in osteoclast-mediated bone resorption,
      in tissue specimens of patients with BON (n=9; four male, five female; mean
      age=69.2 years) and IORN (n=10; nine male, one female; mean age=60.5 years), and
      compared the results with control specimens (n=8; six male, two female; mean
      age=60 years). In all cases, osteoclasts were the predominant cell type
      expressing cathepsin K. For semiquantitative analysis, we therefore defined
      osteoclasts as multinuclear giant cells attached to the bone and expressing
      cathepsin K. Significantly higher numbers of osteoclasts were found for both
      types of osteonecrosis when compared with the control group (BON+IORN vs
      controls: P=0.0000036). Within the pathological lesions, IORN cases exhibited
      significantly less osteoclasts than BON (P=0.00097). Our study verified increased
      numbers of osteoclasts in patients suffering from BON and IORN. Although it is
      known that bisphosphonates (and to a lesser extent, irradiation, too) decrease
      osteoclast function, these findings suggest a critical involvement of osteoclasts
      in the mechanisms of bone destruction in the respective lesions.

PMID- 16957936
TI  - Sources of variation in multi-centre brain MTR histogram studies: body-coil
      transmission eliminates inter-centre differences.
AB  - OBJECT: 1. Identify sources of variation affecting Magnetisation Transfer Ratio
      (MTR) histogram reproducibility between-centres. 2. Demonstrate complete
      elimination of inter-centre difference. MATERIALS AND METHODS: Six principle
      sources of variation were summarised and analysed. These are: the imager coil
      used for radiofrequency (RF) transmission, imager stability, the shape and other
      parameters describing the Magnetisation Transfer (MT) pulse, the MT sequence used
      (including its parameters), the image segmentation methodology, and the histogram
      generation technique. Transmit field nonuniformity and B1 errors are often the
      largest factors. PLUMB (Peak Location Uniformity in MTR histograms of the Brain)
      plots are a convenient way of visualising differences. Five multi-centres studies
      were undertaken to investigate and minimise differences. RESULTS: Transmission
      using a body coil, with a close-fitting array of surface coils for reception,
      gave the best uniformity. Differences between two centres, having MR imagers from
      different manufacturers, were completely eliminated by using body coil
      excitation, making a small adjustment to the MT pulse flip angle, and carrying
      out segmentation at a single centre. Histograms and their peak location and
      height values were indistinguishable. CONCLUSIONS: Body coil excitation is
      preferred for multi-centre studies. Analysis (segmentation and histogram
      generation) should ideally be carried out at a single site.

PMID- 16957937
TI  - Small-animal MRI: signal-to-noise ratio comparison at 7 and 1.5 T with multiple
      animal acquisition strategies.
AB  - OBJECTIVE: The purpose of this study was to compare the signal-to-noise ratio
      (SNR) of phantom and rat brain images performed at 1.5 T on a clinical MR system
      and at 7 T on a small-animal experimental system. Comparison was carried out by
      taking into account SNR values based on a single sample acquisition at 1.5 and 7
      T as well as on simultaneous imaging of multiple samples at 1.5 T. METHODS: SNR
      was experimentally assessed on a phantom and rat brains at 1.5 and 7 T using 25
      mm surface coils and compared to theoretical SNR gain estimations. The
      feasibility of multiple-animal imaging, using the hardware capabilities available
      on the 1.5 T system, was demonstrated. Finally, rat brain images obtained on a
      single animal at 7 T and on multiple animals acquired simultaneously at 1.5 T
      were compared. RESULTS: Experimentally determined SNR at 7 T was far below
      theoretical estimations. Taking into account chemical shift, susceptibility
      artifacts and modifications of T1 and T2 relaxation times at higher field, a 7-T
      system holds limited advantage over a 1.5-T system. Instead, a multiple-animal
      acquisition methodology was demonstrated on a clinical 1.5-T scanner. This
      acquisition method significantly increases imaging efficiency and competes with
      single animal acquisitions at higher field. CONCLUSION: Multiple-animal imaging
      using a standard clinical scanner has a great potential as a high-throughput
      acquisition method for small animals.

PMID- 16957938
TI  - The future role of wavefront-guided excimer ablation.

PMID- 16957939
TI  - Removal of traumatic cyclitic membranes: surgical technique and results.
AB  - BACKGROUND: As most patients with a history of open globe injury and judged to
      have cyclitic membrane are denied further surgery because of poor prognosis, a
      technique for creating radial cuts in traumatic cyclitic membranes and its
      results are described. METHOD: This is a retrospective non-comparative
      interventional case series of eight eyes with history of penetrating eye injury
      with fibrovascular membrane over the pars plicata observed during vitrectomy. All
      eyes were hypotonic; two had undergone previous vitrectomy and had developed RD.
      During vitrectomy after penetrating trauma, lens and its capsule or IOL was
      removed, fibrovascular membrane was visualized over pars plicata with the aid of
      external compression and after removal of the center of anterior hyaloid face,
      radial cuts were placed over the membrane. The resulting pieces were removed with
      vitrectomy probe. An encircling buckling element was placed in all eyes. Best
      corrected visual acuity, IOP, and postoperative complications are described.
      RESULTS: Eight eyes of eight patients (F: 3, M: 5) with an age range of 2-22
      years (median: 11.5) with traumatic cyclitic membranes treated with the above
      technique were included in the study. They were followed for 6-18 months (median:
      12 months). Seven patients had visual acuity of light perception to hand motion
      before operation . Preoperative IOP was low in all eyes (2-5 mmHg, median: 4
      mmHg). One eye with a history of large foreign body removal was finally visually
      lost due to PVR. The other eyes had visual acuity of more than 20/100 (more than
      20/60 in six eyes) and a normal IOP (8-20 mmHg, median 11 mmHg) in the last
      visit. CONCLUSION: Placement of radial cuts over traumatic cyclitic membranes
      followed by removal of the pieces is well tolerated by the ciliary epithelium
      with good retaining of its secretory function and normalization of IOP.

PMID- 16957940
TI  - Spinal cord transection inhibits HR reduction in anesthetized rats immersed in an
      artificial CO2-hot spring bath.
AB  - Like humans, the heart rate (HR) of anesthetized rats immersed in CO(2)-water is
      lower than that when immersed in tap water at the same temperature. To
      investigate the afferent signal pathway in the mechanism of HR reduction, Wistar
      rats were anesthetized with urethane and then the spinal cord was transected
      between T(4) and T(5). The animals were immersed up to the axilla in a bathtub of
      tap-water (CO(2) contents: 10-20 mg.l(-1)) or of CO(2)-water (965-1,400 mg.l(-1))
      at 35 degrees C while recording HR, arterial blood pressure, and arterial blood
      gas parameters (PaCO(2), PaO(2), pH). Arterial blood gas parameters did not
      change during immersion, irrespective of CO(2) concentration of the bath water,
      whereas the HR was reduced in the CO(2)-water bath. The inhalation of CO(2)-mixed
      gas (5% CO(2), 20% O(2), 75% N(2)) resulted in increased levels of blood gases
      and an increased HR during immersion in all types of water tested. The HR
      reduction observed in sham transected control animals immersed in CO(2)-water
      disappeared after subsequent spinal cord transection. These results show that the
      dominant afferent signal pathway to the brain, which is involved in inducing the
      reduced HR during immersion in CO(2)-water, is located in the neuronal route and
      not in the bloodstream.

PMID- 16957941
TI  - Modulation of acute inflammation by a chitin-binding lectin from Araucaria
      angustifolia seeds via mast cells.
AB  - The effects of a lectin (AaL) from seeds of Araucaria angustifolia were
      investigated in the model of rat paw edema. In vivo anti-and pro-inflammatory
      activities, role of sugar residues, inflammatory mediators and systemic toxicity
      were assessed. Intravenous injection of AaL (0.1-1 mg/kg) dose-dependently
      inhibited the dextran-induced increase in edema and vascular permeability, which
      were prevented by association of the lectin with its binding sugar N-acetyl
      glucosamine (Glyc-Nac). AaL also significantly inhibited edema induced by
      serotonin (18%) and compound 48/80 (33%), but not edema induced by histamine. In
      contrast, when applied by the s.c. route, AaL evoked a paw edema that peaked 1 h
      later and was partially prevented by association with Glyc-Nac (59%) or by prior
      i.v. administration of the lectin itself (38.8%). This AaL edematogenic activity
      was significantly inhibited by pentoxifylline (44.4%) or dexamethasone (51%) and
      also by depletion of rat paw mast cells (45.6%), but not by L-N-nitro-arginine
      methyl ester or indomethacin, excluding involvement of nitric oxide and
      prostaglandins. Treatment of animals with a single anti-inflammatory dose of AaL
      (1 mg/kg, i.v.) for 7 days did not affect rat corporal mass, liver, kidney,
      spleen or stomach wet weight, blood leukocyte count, and urea, creatinine or
      serum transaminase activity. Systemic toxicity was apparent only at much higher
      doses (LD50=88.3 mg/kg) than those required for the anti-inflammatory effect.
      Summarizing, AaL exerts anti-and pro-edematogenic actions via interaction with
      its specific lectin domain. These actions may share a common pathway involving
      either activation or inhibition of inflammatory mediators from resident mast
      cells.

PMID- 16957943
TI  - Temperature acclimation alters cardiac performance in the lobster Homarus
      americanus.
AB  - The American lobster is a poikilotherm that inhabits a marine environment where
      temperature varies over a 25 degrees C range and depends on the winds, the tides
      and the seasons. To determine how cardiac performance depends on the water
      temperature to which the lobsters are acclimated we measured lobster heart rates
      in vivo. The upper limit for cardiac function in lobsters acclimated to 20
      degrees C is approximately 29 degrees C, 5 degrees C warmer than that measured in
      lobsters acclimated to 4 degrees C. Warm acclimation also slows the lobster heart
      rate within the temperature range from 4 to 12 degrees C. Both effects are
      apparent after relatively short periods of warm acclimation (3-14 days). However,
      warm acclimation impairs cardiac function at cold temperatures: following several
      hours exposure to frigid (<5 degrees C) temperatures heart rates become slow and
      arrhythmic in warm acclimated, but not cold acclimated, lobsters. Thus,
      acclimation temperature determines the thermal limits for cardiac function at
      both extremes of the 25 degrees C temperature range lobsters inhabit in the wild.
      These observations suggest that regulation of cardiac thermal tolerance by the
      prevailing environmental temperature protects against the possibility of cardiac
      failure due to thermal stress.

PMID- 16957944
TI  - Whole-organism studies of adhesion in pad-bearing lizards: creative evolutionary
      solutions to functional problems.
AB  - Understanding the evolution of complex functional traits is a challenge for
      evolutionary physiology. Here we investigate the evolution of subdigital toepads
      in lizards, which have arisen independently at least three times, although with
      subtle anatomical differences. Some designs (anole, gecko) appear functionally
      equivalent, whereas other designs (skink) are inferior. The functional
      equivalence of geckos and anoles highlights the creative aspect of the
      evolutionary process in that these two groups have arrived at the same functional
      endpoint along very different trajectories. However, this functional equivalence
      does not result in equivalence for performance at whole-organism tasks (e.g.,
      running uphill), as the evolution of behavior (e.g., toe-furling) has enabled
      geckos to be superior climbers than anoles. We also show that adaptive increases
      in the toepad size within a closely related lizard genus (Anolis) has resulted in
      concomitant evolution of enhanced clinging ability and increased perch heights. A
      third insight is that pad-bearing geckos are capable of carrying tremendous loads
      (up to 250% of body weight) up smooth surfaces, and that the toepad itself does
      not appear limiting. This comparative and whole-organism approach to lizard
      toepads underscores how organisms can evolve multiple solutions to evolutionary
      problems.

PMID- 16957942
TI  - Topoisomerase II beta expression level correlates with doxorubicin-induced
      apoptosis in peripheral blood cells.
AB  - Anthracyclines are widely used in oncology. Both the response and side-effects of
      anthracyclines are individually variable, but determinants or predictive markers
      of this variability are not available. We investigated the variability in the
      expression of the anthracycline targets topoisomerases II (topo II) alpha and
      beta and its significance for the apoptotic response following exposure to the
      anthracycline doxorubicin. Only topo II beta protein expression was detected in
      peripheral blood cells. Usually considered a constitutively expressed protein,
      topo II beta varied 3-, 18-, and 16-fold on the mRNA, protein and activity
      levels, respectively, among the volunteers tested. In addition, the expression of
      topo II beta was modified by several mitogens, suggesting a role in the
      regulation of cell cycle. Strikingly, topo II beta activity correlated
      statistically significantly with the apoptotic response in peripheral blood
      leukocytes exposed to 1 microM doxorubicin. A longitudinal study in a subset of
      study subjects demonstrated that 30% of the topo II expression variability may be
      inherited. However, resequencing of the TOP2B gene in 48 unrelated individuals
      revealed only 8 gene variants, none of them with obvious effects on the
      expression or protein sequence of topo II beta. Taken together, the apoptotic
      response to doxorubicin in peripheral blood cells may be mediated by topo II
      beta. The expression level of topo II beta is intra- and inter-individually
      variable, and may in part determine the apoptotic response to doxorubicin and
      other anthracyclines.

PMID- 16957945
TI  - Dynamic control of the lumbopelvic complex; lack of reliability of established
      test procedures.
AB  - Impairment of the dynamic control of the lumbopelvic complex in LBP has gained
      increased focus both clinically and experimentally. The objectives of this study
      were to determine the reliability of inclinometry as a measure of dynamic
      lumbopelvic control. Lumbopelvic reposition accuracy during pelvic tilts was
      measured in 39 healthy subjects using an inclinometer attached to the skin at S2
      level. The reposition accuracy was measured in sitting, standing and supported
      standing. Tests were performed three times with a 20 min recess between tests.
      Only data from the last two test sequences were used in order to account for
      learning effects. Intraclass correlation coefficients were low for the sitting
      (0.54) and supported standing positions (0.36). In the standing position, a
      significant difference between test and retest was observed (P = 0.003) and
      further reliability analysis was therefore abandoned. It is concluded that
      inclinometry is not reliable for measuring the dynamic lumbopelvic control in any
      of the test positions and prior work utilising inclinometry to evaluate dynamic
      lumbopelvic control should be interpreted with caution.

PMID- 16957949
TI  - [A complication during kyphoplasty. Cement penetration through the azygos vein
      into the superior vena cava].
AB  - A 59-year-old woman had a nontraumatic osteoporotic fracture of the seventh
      thoracic vertebral body. Despite correct operative technique, in the course of
      kyphoplasty cement was dislocated through the segment vein into the azygos vein
      and from there into the superior vena cava. The patient was free of
      cardiopulmonary symptoms throughout. Oral anticoagulation was administered for 3
      months to prevent thromboembolism, and regular clinical and echocardiographic
      follow-up examinations were also performed during this period.

PMID- 16957950
TI  - [Urinary tract infection: Weimar 2006. International symposium].

PMID- 16957946
TI  - Transpedicle body augmenter in painful osteoporotic compression fractures.
AB  - Osteoporotic compression fractures (VCFs) can result in progressive kyphosis and
      chronic pain. Polymethylmethacrylate has been used for augmentation of VCFs;
      however, there are cement complications, and long-term fracture healing is
      unknown. The transpedicle body augmenter (TpBA), a porous titanium spacer, has
      been reported as an internal support to reconstruct the vertebral body combining
      short segment fixation in burst fracture. We retrospectively reviewed
      radiographic and clinical results of TpBA vertebroplasty for single symptomatic
      VCF in 80 patients. Manual reduction and TpBA vertebroplasty via a paramedian
      incision with blunt dissection was done. Mean age was 72.3 years (range 51-87
      years), and female-male ratio was 66:14. The mean symptom duration was 5 months,
      and follow-up 44 months. Peri-operative variables and radiographic and clinical
      results were evaluated. The average operation time was 26.1 min, blood loss 92
      cc, and hospitalization 2.3 days. No patient had neurological deterioration. TpBA
      was found sinking into vertebral body initially, then locked by residual cortex,
      and finally stabilized within the vertebra. There was no dislodgement of TpBA in
      the final visit. Sixty-two patients (77.5%) could walk within 3-6 h after
      operation and the others within 24 h. The anterior vertebral restoration was 8.0
      mm initially and 6.1 mm at final follow-up. Wedge angle correction was 11.5
      degrees initially and 9.4 degrees at final follow-up. Pain, by the visual analog
      scale, was 8.6 pre-operatively, 2.5 at day 7 follow-up, and 2.9 at final follow
      up. By the questionnaire, 72 of 76 respondents reported a decrease in discomfort
      after TpBA vertebroplasty, and 63 of 76 patients reported a return to normal
      activity after operation. The final satisfaction rate was 93.4%. TpBA
      vertebroplasty led to early and medium-term clinical improvement and anatomic
      restoration of painful VCFs.

PMID- 16957951
TI  - Intrinsic versus extrinsic influences in the development of neuronal maps.
AB  - Accumulating evidence suggests that the plasticity of extrinsic thalamocortical
      inputs in cortical layer IV may be guided or instructed by earlier plasticity
      events in the intrinsic, horizontal connections within the extragranular cortical
      layers. We analyse a rate-based model of the plasticity of a set of extrinsic
      afferents in the presence of a pre-existing (and fixed) plexus of intrinsic,
      overall excitatory horizontal connections between a set of target neurons. We
      determine conditions under which afferent synaptic pattern formation respects
      this pre-existing lateral structure. We find three broad regimes under which
      extrinsic afferent plasticity may violate this structure: the initial pattern of
      extrinsic afferent innervation of the target cells is far from balanced; the gain
      of the extrinsic afferents greatly exceeds the overall scale of the strength of
      lateral excitation; the target cell horizontal coupling matrix is sparse. If none
      of these conditions is satisfied, then extrinsic afferent plasticity respects the
      pre-existing lateral connectivity, so that afferent synaptic pattern formation
      conforms to the pattern of lateral excitation.

PMID- 16957952
TI  - Functional conservation of zinc-finger homeodomain gene zfh1/SIP1 in Drosophila
      heart development.
AB  - Comparative genetic studies of diverse animal model systems have revealed that
      similar developmental mechanisms operate across the Metazoa. In many cases, the
      genes from one organism can functionally replace homologues in other phyla, a
      result consistent with a high degree of evolutionarily conserved gene function.
      We investigated functional conservation among the Drosophila zinc-finger
      homeodomain protein 1 (zfh1) and its mouse functional homologue Smad-interacting
      protein 1 (SIP1). Northern blot analyses of SIP1 expression patterns detected
      three novel variants (8.3, 2.7, and 1.9 kb) in addition to the previously
      described 5.3 kb SIP1 transcript. The two shorter novel SIP1 transcripts were
      encountered only in developing embryos and both lacked zinc-finger clusters or
      homeodomain regions. The SIP1 transcripts showed complex embryonic expression
      patterns consistent with that observed for Drosophila zfh1. They were highly
      expressed in the developing nervous systems and in a number of mesoderm-derived
      tissues including lungs, heart, developing myotomes, skeletal muscle, and
      visceral smooth muscle. The expression of the mammalian 5.3 kb SIP1 transcript in
      Drosophila zfh1 null mutant embryos completely restored normal heart development
      in the fly, demonstrating their functional equivalence in cardiogenic pathways.
      Our present data, together with the previously described heart defects associated
      with both SIP1 and Drosophila zfh1 mutations, solidify the conclusion that the
      zfh1 family members participate in an evolutionary conserved program of metazoan
      cardiogenesis.

PMID- 16957953
TI  - Fixed versus dynamic orientations in environmental learning from ground-level and
      aerial perspectives.
AB  - Ground-level and aerial perspectives in virtual space provide simplified
      conditions for investigating differences between exploratory navigation and map
      reading in large-scale environmental learning. General similarities and
      differences in ground-level and aerial encoding have been identified, but little
      is known about the specific characteristics that differentiate them. One such
      characteristic is the need to process orientation; ground-level encoding (and
      navigation) typically requires dynamic orientations, whereas aerial encoding (and
      map reading) is typically conducted in a fixed orientation. The present study
      investigated how this factor affected spatial processing by comparing ground
      level and aerial encoding to a hybrid condition: aerial-with-turns. Experiment 1
      demonstrated that scene recognition was sensitive to both perspective (ground
      level or aerial) and orientation (dynamic or fixed). Experiment 2 investigated
      brain activation during encoding, revealing regions that were preferentially
      activated perspective as in previous studies (Shelton and Gabrieli in J Neurosci
      22:2711-2717, 2002), but also identifying regions that were preferentially
      activated as a function of the presence or absence of turns. Together, these
      results differentiated the behavioral and brain consequences attributable to
      changes in orientation from those attributable to other characteristics of ground
      level and aerial perspectives, providing leverage on how orientation information
      is processed in everyday spatial learning.

PMID- 16957954
TI  - Biased representations of the spatial structure of navigable environments.
AB  - Recent studies (e.g., Shelton & McNamara in Cognitive Psychology, 43(4), 274-310,
      2001; Valiquette, McNamara, & Smith in Memory and Cognition, 31(3), 479-489,
      2003) have demonstrated that judgments of relative direction (JRD) access a
      single enduring orientation-dependent allocentric representation of the layout of
      objects in an environment, regardless of whether the space is viewed from one or
      multiple vantage points. Two experiments tested the limits of this phenomenon. In
      both experiments participants learned the locations of objects in a large room
      from two views: one view was aligned with salient environmental frames of
      reference (edges of the mat on which objects were placed and walls of the
      enclosing room) and expected to be preserved in long-term memory; the other view
      was misaligned and not expected to be preserved in long-term memory. The first
      experiment demonstrated that performing JRD between studying the misaligned view
      and studying the aligned view did not result in the misaligned view being
      maintained in long-term memory. The second experiment demonstrated that after
      studying the layout extensively from the misaligned view, 30 s of exposure to the
      aligned view (with no instructions to learn the layout from that view) resulted
      in the aligned but not the misaligned view being preserved in long-term memory.
      These findings indicate that the human spatial memory and navigation system is
      strongly biased to represent the spatial structure of navigable environments with
      reference directions or axes that are aligned with salient environmental frames
      of reference.

PMID- 16957955
TI  - Imaginal repositioning in everyday environments: effects of testing method and
      setting.
AB  - Two experiments examined spatial knowledge access after imagined perspective
      switches in everyday environments. Blindfolded volunteers had to point to target
      objects in a well-known surrounding while imagining being repositioned into
      different spatial perspectives defined as self-rotations of the observer in the
      horizontal plane (0 degrees , 45 degrees , and 135 degrees ). Testing was either
      conducted in the space the target locations had been learned in (actual room
      testing), or while participants were away from this room, but should imagine
      being situated there (remote room testing). Experiment 1, in which perspective
      switches were tested on a trial-to-trial basis, revealed increases in pointing
      latency and error as a function of the amount of angular disparity between real
      and imagined perspective under actual and remote room conditions. Experiment 2,
      in which knowledge access was tested in blocks of multiple trials per
      perspective, showed increases in pointing latency with angular disparity for
      actual space testing, and to a much lesser degree for remote space testing.
      Implications of both findings for theoretical accounts of knowledge access after
      imaginal perspective switches are discussed, and recommendations for using
      different testing methods and settings are given.

PMID- 16957956
TI  - Humans do not switch between path knowledge and landmarks when learning a new
      environment.
AB  - Using a metric shortcut paradigm, we have found that like honeybees (Dyer in
      Animal Behaviour 41:239-246, 1991), humans do not seem to build a metric
      "cognitive map" from path integration. Instead, observers take novel shortcuts
      based on visual landmarks whenever they are available and reliable (Foo, Warren,
      Duchon, & Tarr in Journal of Experimental Psychology-Learning Memory and
      Cognition 31(2):195-215, 2005). In the present experiment we examine whether
      humans, like ants (Wolf & Wehner in Journal of Experimental Biology 203:857-868,
      2000), first use survey-type path knowledge, built up from path integration, and
      then subsequently shift to reliance on landmarks. In our study participants
      walked in an immersive virtual environment while head position and orientation
      were recorded. During training, participants learned two legs of a triangle with
      feedback: paths from Home to Red and Home to Blue. A configuration of colored
      posts surrounded the Red location. To test reliance on landmarks, these posts
      were covertly translated, rotated, or left unchanged during six probe trials.
      These probe trials were interspersed during the training procedure to measure
      changes over learning. Dependence on visual landmarks was immediate and sustained
      during training, and no significant learning effects were observed other than a
      decrease in hesitation time. Our results suggest that while humans have at least
      two distinct navigational strategies available to them, unlike ants, a
      computationally-simpler landmark strategy dominates during novel shortcut
      navigation.

PMID- 16957957
TI  - Rechallenging subjects with occupational asthma due to toluene diisocyanate
      (TDI), after long-term removal from exposure.
AB  - OBJECTIVES: Aims of this study were to define (1) whether toluene diisocyanate
      (TDI) bronchial hyper-responsiveness persists in subjects with occupational
      asthma after long-term cessation of exposure; (2) whether evolution of specific
      bronchial TDI sensitization and symptoms and functional abnormalities of asthma
      were coincident, and (3) the determinants at the time of diagnosis of patients'
      outcome. METHODS: Twenty-five nonatopic spray painters with occupational asthma
      due to TDI were re-examined 58 +/- 7 (46-73) months after removal from exposure.
      On both examinations, the severity of asthmatic symptoms and the need for
      antiasthma treatment over the past 12 months were graded and lung function tests,
      measurement of airway responsiveness to methacholine (PD(20)), circulating total
      IgE and TDI-HSA specific IgE, skin tests with common inhalant allergens and
      specific bronchial challenge with TDI were carried out. RESULTS: Seven subjects
      were still TDI-reactors and 18 lost reactivity to it. All persistent reactors had
      still asthma and their symptom score, medication score, FEV(1), PD(20) and serum
      IgE were unchanged between assessments. In the 18 subjects no longer responsive
      to TDI, 8 had still features of asthma: their symptom and medication score had
      improved significantly, but FEV(1), PD(20) and serum IgE had not significantly
      changed; the other ten patients no longer reactors to TDI were also asymptomatic
      and their PD(20) had become normal. The duration of symptomatic exposure to TDI
      was the only feature at diagnosis that differentiated patients with persistent
      TDI airway hyper-responsiveness and asthma from those who were no longer
      responsive to TDI but still asthmatic and those who were no longer responsive to
      TDI and no longer asthmatic (4 +/- 1.6; 2.1 +/- 0.8; 0.6 +/- 0.3 years,
      respectively; p < 0.001). CONCLUSION: our study demonstrates that airway
      sensitization to TDI and symptoms and functional airway abnormalities of asthma
      can persist for years after cessation of exposure and may have different outcome.
      If avoidance of the offending agent takes place within few months after the
      development of symptoms, remission of asthma and of TDI bronchial hyper
      responsiveness can occur, whereas waiting for years makes it too late to cure
      asthma and, in the end, to reverse specific sensitization.

PMID- 16957958
TI  - [Anhidrotic ectodermal dysplasia (Christ-Siemens-Touraine-Syndrom)].

PMID- 16957959
TI  - [Unilateral laterothoracic exanthema].

PMID- 16957960
TI  - [Double-lip and blepharochalasis: Ascher syndrome in a 13 year-old female
      patient].

PMID- 16957961
TI  - [Interdisciplinary training program for adults with psoriaisis: six months follow
      up].
AB  - BACKGROUND: The aim of our pilot study was to evaluate effects of an
      interdisciplinary training program for adult psoriasis patients after six months
      follow-up. SUBJECTS AND METHODS: Eleven patients with psoriasis participated in
      an interdisciplinary training program over a weekend taught by dermatologists,
      psychologists/psychiatrists, and dieticians. Six months follow-up was performed
      with a questionnaire. RESULTS: The knowledge acquired improved the cooperation
      with the treating dermatologist (7 of 11), the patients' ability to cope with
      their disease (11 of 11), and their ability to improving their health status (8
      of 11). Their general well-being was increased (9 of 11) and they could better
      care for their skin disease because they better understood the need for care (9
      of 11), and could better judge the best approach for various levels of disease
      activity (8 of 11). CONCLUSION: These data show early benefits and suggest such a
      longer lasting effect of this type of psoriasis training and prevention program.
      Further studies with larger samples and control parameters will have to examine
      if these results can be confirmed.

PMID- 16957964
TI  - Lymph node status in patients with submucosal gastric cancer.
AB  - BACKGROUND: The aim of this study was to clarify the lymph node status in
      patients with submucosal gastric cancer. METHODS: Between April 1994 and December
      1999, 615 patients with histologically proven submucosal gastric cancer who
      underwent curative resection were included in this study. The results of the
      surgery and predictive factors for lymph node metastasis were evaluated by
      univariate and multivariate analyses. The accuracy of the predictive factors was
      assessed in a second population of a further 186 patients. RESULTS: Lymph node
      metastasis was observed in 119 patients (19.3%). Multivariate analysis showed
      that pathologic tumor diameter (> or = 20 mm) and lymphatic invasion were
      independent predictive factors for lymph node metastasis. The incidence of lymph
      node metastasis without these 2 predictive factors was 1.8% (2 of 113), and it
      was 51.2% (85 of 166) with the 2 predictive factors, 9.5% (14 of 148) in tumors <
      20 mm in diameter, and 5.3% (22 of 414) in tumors without lymphatic invasion.
      Among patients with a tumor < 20 mm in diameter, the incidence of lymph node
      metastasis was significantly reduced in those with a differentiated tumor: 4.2%
      (4 of 95). These results were almost identical to those observed in the second
      population. CONCLUSIONS: Lymph node status can be accurately predicted on the
      basis of pathologic tumor diameter < 20 mm, lymphatic invasion (absence), and
      histological type (differentiated) in patients with submucosal gastric cancer.
      Less extensive surgery for these patients might be reconsidered after
      confirmation of the reproducibility of the results of this study by an
      appropriately designed prospective clinical trial.

PMID- 16957965
TI  - Splenectomy during secondary cytoreduction for ovarian cancer disease recurrence:
      surgical and survival data.
AB  - BACKGROUND: Ovarian cancer disease recurs predominantly in the abdomen, with the
      spleen usually involved as part of a vast spread of upper-abdominal disease or,
      less frequently, as an isolated site of disease recurrence. Very few reports are
      available in the literature on the outcome of patients subjected to splenectomy
      during secondary cytoreduction. The aim of this study was to identify prognostic
      factors and to review surgical and clinical data in order to identify those
      patients who would benefit the most from splenectomy during secondary
      cytoreduction. METHODS: This was a retrospective review of platinum-sensitive
      recurrent epithelial ovarian cancer patients who underwent splenectomy as part of
      secondary cytoreduction. Surgical and survival data were recorded. RESULTS:
      Twenty-four patients were identified. Multiple site disease recurrence was
      observed in 15 patients. The spleen was involved at the hilus in 12 patients;
      surface and intraparenchymal metastases were equally present. Optimal
      cytoreduction was achieved in all patients. At a median follow-up of 30 months,
      median progression-free and overall survival from the time of secondary surgery
      were 34 and 56 months, respectively. Overall survival was significantly
      correlated to residual disease at secondary surgery, disease-free survival,
      consolidation chemotherapy, and type of adjuvant therapy. CONCLUSIONS:
      Splenectomy as part of secondary cytoreduction is a feasible and safe procedure.
      Secondary cytoreduction in selected groups of patients is confirmed to be
      associated with high long-term survival rates even when aggressive surgery of the
      upper abdomen is required.

PMID- 16957966
TI  - Impact of surgery on advanced gastrointestinal stromal tumors (GIST) in the
      imatinib era.
AB  - BACKGROUND: The role for surgery in patients with "unresectable" gastrointestinal
      stromal tumors (GIST) treated with imatinib is still not defined. The objective
      of this retrospective study was to evaluate the feasibility and benefit of this
      secondary surgery. METHODS: Progression-free survival (PFS) in a group of
      patients who underwent secondary surgery was compared to that of patients treated
      exclusively with imatinib. RESULTS: Of 180 patients with unresectable GIST
      treated with Imatinib, 22 (12%) underwent secondary surgery, following which one
      patient achieved a complete radiological response, 19 achieved a partial response
      (PR), in one patient the disease was stable, and in one patient there was
      reactivation of local occlusive disease after an initial PR. No patient with
      overall progression was to undergo surgery. At the beginning of imatinib therapy,
      five patients with metastases underwent emergency surgery [hemorrhage (n = 3) due
      to rupture of large necrotic masses], which ultimately resulted in three of the
      five patients dying postoperatively. A macroscopically complete resection was
      achieved in all primary tumors (5/5) and in ten of the 17 metastases.
      Pathological analysis revealed two complete response (CR) and 17 PR, and no
      treatment effect was evidenced in three patients. Two-year overall survival after
      surgery was 62%. The median PFS calculated from the initiation of imatinib
      therapy was 18.7 months for all operated patients and 23.4 months after planned
      surgery. CONCLUSION: Primary tumors that become amenable to surgery with prior
      imatinib therapy, evolving necrosis and localized progression (to avoid life
      threatening complications) could benefit from this secondary surgery. For the
      majority of other residual lesions, the potential benefit of secondary surgery
      should be evaluated in randomized studies in the future since PFS is similar to
      that reported among non-operated patients.

PMID- 16957967
TI  - Treatment of advanced gastrointestinal stromal tumor: a marriage of targeted
      therapy and surgery?

PMID- 16957968
TI  - Utilizing quantitative polymerase chain reaction to evaluate prostate stem cell
      antigen as a tumor marker in pancreatic cancer.
AB  - BACKGROUND: Real-time quantitative polymerase chain reaction (qPCR) may prove to
      be a sensitive technique by which to evaluate potential tumor markers in
      pancreatic cancer. METHODS: The prostate stem cell antigen (PSCA) gene was
      identified as a marker highly expressed in pancreatic adenocarcinoma and not
      normal pancreas. RNA from pancreatic and nonpancreatic cancer cell lines as well
      as tissue and blood from pancreatic cancer and control patients was reverse
      transcribed and PSCA quantified by qPCR. RESULTS: Individual operator experience
      affects the results of qPCR, with significantly different copy numbers at
      experiment numbers 5, 15, and 40. Five of six pancreatic cell lines had
      PSCA/actin ratios 10-fold greater than nonpancreatic cancer lines. Mean PSCA
      expression in pancreatic tumor tissue was significantly higher (P < 0.05,
      Student's t-test) than in the tissue of benign pancreatic processes. The close
      correlation of PSCA/actin copy number with number of tumor cells in the blood was
      demonstrated by regression analysis (r = 0.768, P = 0.0001). PSCA copy number was
      significantly higher in the blood of patients with metastatic pancreatic cancer
      than in that of normal patients (P < 0.05, Student's t-test). CONCLUSIONS: Such
      trends suggest that PSCA may prove to be a valuable pancreatic cancer tumor
      marker. More generally, the technique of qPCR is shown to provide a sensitive
      method of evaluating markers in cancer patients.

PMID- 16957969
TI  - Prospective randomized clinical trial comparing intradermal, intraparenchymal,
      and subareolar injection routes for sentinel lymph node mapping and biopsy in
      breast cancer.
AB  - BACKGROUND: Multiple injection routes, including intradermal (ID),
      intraparenchymal (IP), and subareolar (SA), are used for 99mTc-sulfur colloid
      administration for sentinel lymph node (SLN) mapping and biopsy in breast cancer.
      The aim of this study was to compare localization by ID, IP, and SA injection
      routes based on preoperative lymphoscintigraphy and intraoperative
      identification. METHODS: Four hundred prospectively randomized breast cancers
      underwent SLN mapping and biopsy. RESULTS: Preoperative lymphoscintigraphy
      demonstrated localization to the axilla in 126/133 (95%) ID, 82/132 (62%) IP, and
      96/133 (72%) SA (P < 0.001 ID vs. IP and ID vs. SA; P = 0.081 IP vs. SA), with a
      mean duration of preoperative lymphoscintigraphy of 139 +/- 18 minutes. Mean time
      to first localization when localization was demonstrated on preoperative
      lymphoscintigraphy was 8 +/- 14 minutes for ID, 53 +/- 49 for IP, and 22 +/- 29
      for SA (P < 0.001 ID vs. IP and ID vs. SA; P = 0.003 IP vs. SA). Intraoperative
      identification of a SLN at the time of SLN biopsy was successful in 133/133
      (100%) ID, 121/134 (90%) IP, and 126/133 (95%) SA (P < 0.001 ID vs IP; P = 0.014
      ID vs. SA; P = 0.168 IP vs. SA), with a mean time from injection of 99mTc-sulfur
      colloid to start of SLN biopsy of 288 +/- 71 minutes. Mean intraoperative time to
      harvest the first SLN was 9 +/- 4 minutes for ID, 13 +/- 6 for IP, and 12 +/- 6
      for SA (P < 0.001 ID vs. IP and ID vs. SA; P = 0.410 IP vs. SA). CONCLUSIONS: The
      ID injection route demonstrated a significantly greater frequency of
      localization, decreased time to first localization on preoperative
      lymphoscintigraphy, and decreased time to harvest the first SLN. This represents
      the first prospective randomized clinical trial to confirm superiority of the ID
      route for administration of 99mTc-sulfur colloid during SLN mapping and biopsy in
      breast cancer.

PMID- 16957970
TI  - Learning curve for percutaneous radiofrequency ablation of pulmonary metastases
      from colorectal carcinoma: a prospective study of 70 consecutive cases.
AB  - BACKGROUND: Percutaneous radiofrequency ablation (RFA) for inoperable colorectal
      pulmonary metastases is associated with a morbidity rate of 30% to 40%. A
      learning curve in this treatment approach has not been documented before.
      METHODS: The clinical and treatment-related data regarding 70 consecutive
      percutaneous RFA procedures for inoperable colorectal pulmonary metastases were
      collected prospectively. A comparison between the initial 35 cases (group 1) and
      the subsequent 35 cases (group 2) was performed. Univariate and multivariate
      analyses were conducted to identify the significant risk factors for overall
      morbidity, pneumothorax, and chest drain requirement. RESULTS: There was no
      hospital mortality. The overall morbidity rate was 37%. The rate of pneumothorax
      was 27%. Twelve patients (17%) required chest drain insertion for pneumothorax.
      There was a significant decline in the incidence of overall morbidity,
      pneumothorax, and chest drain requirement in group 2 as compared with group 1.
      Both the number of lung metastases ablated and the RFA treatment period (group 1
      vs. group 2) were independent risk factors for overall morbidity, pneumothorax,
      and chest drain requirement. Distribution of lung metastases (unilateral vs.
      bilateral) was an independent risk factor for overall morbidity and pneumothorax,
      but not for chest drain requirement. CONCLUSIONS: There is a learning curve for
      percutaneous lung RFA. With accumulated experience in this procedure, a low
      morbidity rate can be achieved.

PMID- 16957973
TI  - Suicide by shooting and gun ownership (licenses) in Austria: Would gun
      restriction help?

PMID- 16957975
TI  - TB or not TB?

PMID- 16957974
TI  - Molecular and clinical aspects of iron homeostasis: From anemia to
      hemochromatosis.
AB  - The discovery in recent years of a plethora of new genes whose products are
      implicated in iron homeostasis has led to rapid expansion of our knowledge in the
      field of iron metabolism and its underlying complex regulation in both health and
      disease. Abnormalities of iron metabolism are among the most common disorders
      encountered in practical medicine and may have significant negative impact on
      physical condition and life expectancy. Basic insights into the principles of
      iron homeostasis and the pathophysiological and clinical consequences of iron
      overload, iron deficiency and misdistribution are thus of crucial importance in
      modern medicine. This review summarizes our current understanding of human iron
      metabolism and focuses on the clinically relevant features of hereditary and
      secondary hemochromatosis, iron deficiency anemia, anemia of chronic disease and
      anemia of critical illness. The interconnections between iron metabolism and
      immunity are also addressed, in as much as they may affect the risk and course of
      infections and malignancies.

PMID- 16957976
TI  - Suicide by shooting is correlated to rate of gun licenses in Austrian counties.
AB  - OBJECTIVES: Shooting as method of suicide has increased considerably in Austria
      over recent decades and represented 23.5% of all suicides among men during the
      period 1990-2000. It is thought that the availability of guns could lead to their
      use in acts of suicide, and therefore we investigated the numbers of gun licenses
      (which constitutes ownership of guns and permission to carry a gun) in the nine
      Austrian counties and their correlation with suicides by shooting and other
      methods. METHODS: We studied registered suicides, including the method used,
      between 1990 and 2000 in Austria and the numbers of gun licenses held in the nine
      counties of Austria in the same period. RESULTS: We found a strong correlation
      between the average gun license rate for the period 1990-2000 and suicides by
      shooting (r = 0.967), and only very weak correlation, and for some of the years
      under investigation a negative correlation, with other methods of committing
      suicide (r = 0.117) and the suicide rate in general (r = 0.383). CONCLUSIONS: As
      shooting as a method of suicide has increased in Austria in recent decades, and
      is a highly lethal method, the finding that the shooting suicide rate is related
      to the extent of gun ownership deserves attention, especially as there is
      evidence that restriction of gun ownership is an important factor in suicide
      prevention.

PMID- 16957977
TI  - Albumin-glutaraldehyde bioadhesive ("Bioglue") for prevention of postoperative
      complications after stapled hemorrhoidopexy: A randomized controlled trial.
AB  - BACKGROUND: Hemorrhoidopexy using the circumferential stapler is an established
      method for surgical treatment of patients with prolapsing hemorrhoids. Despite
      its advantages, complications such as anal canal stenosis, hemorrhage and
      anastomosis leak with eventual intrapelvic sepsis can cause serious postoperative
      problems. The aim of this study was to evaluate the utility of a surgical
      adhesive, the biological albumin-glutaraldehyde glue "Bioglue", in reduction of
      these postoperative complications. PATIENTS AND METHODS: Between January 2002 and
      November 2004, 200 patients undergoing stapled hemorrhoidopexy were enrolled in a
      prospective, randomized clinical trial. One hundred patients were randomly
      assigned to the control group; the study group consisted of 100 patients who
      received Bioglue in the mucosa anastomosis area. All patients received
      standardized postoperative analgesic, laxative and antibiotic treatment. We then
      evaluated the two groups for postoperative complications (after surgery and 6
      months postoperatively). RESULTS: From the control group (no Bioglue
      application), two patients presented with anal stenosis, two with hemorrhage,
      three had anastomosis leak and one had thrombosis, whereas none of the patients
      from the Bioglue group had any of these complications. Both groups had patients
      with severe postoperative pain (3 each) and fecal incontinence (1 patient each).
      The overall difference in the number of complications in the two groups was
      statistically significant (p < 0.05). CONCLUSION: In this first study using
      Bioglue in patients undergoing circumferential stapled hemorrhoidopexy we have
      shown that application of the glue is effective in reducing postoperative
      complications.

PMID- 16957978
TI  - Osteonecrosis of the jaws and bisphosphonate treatment in cancer patients.
AB  - PURPOSE: Osteonecrosis of the jaws is described as an intraoral complication
      after administration of intravenous nitrogen-containing bisphosphonates. In a
      retrospective study, patients with osteonecrosis of the jaws after bisphosphonate
      treatment were evaluated with regard to diagnostic investigations and therapeutic
      management. PATIENTS AND METHODS: Seventeen patients with osteonecrosis of the
      jaws after bisphosphonate treatment who were referred to our department between
      July 2004 and June 2005 were included in this study. Computer tomography,
      magnetic resonance imaging, scintigraphy, bacteriology and biopsy were used in
      diagnostic evaluation. All patients were treated surgically. RESULTS: The reasons
      for bisphosphonate treatment were multiple myeloma in 12 patients, breast cancer
      with bone metastasis in four patients and histiocytosis X in one patient. Five
      patients had received intravenous pamidronate and 12 patients zoledronic acid.
      The median number of treatment cycles for pamidronate was 36 times (range 4-100)
      in 38 months (range 4-100). Zolendric acid was given 23.5 times (range 5-39) in
      26 months (range 5-39). Nine patients had a lesion in the mandible, eight in the
      maxilla. Clinical symptoms were exposed bone, pain and local inflammation of the
      mucosa. Computer tomography showed sclerotic areas in the osteonecrosis zone. The
      biopsy did not show a metastatic lesion. Sequestrectomy and decortication was
      adequate in the follow-up. CONCLUSION: Nitrogen-containing bisphosphonates appear
      to be associated with the risk of developing osteonecrosis of the jaws. To reduce
      this risk, patients should be evaluated by a dentist before beginning treatment
      with intravenous bisphosphonates.

PMID- 16957979
TI  - Exploratory thoracotomy and its influence on the survival of patients with lung
      cancer.
AB  - PURPOSE: To evaluate diagnostic procedures, reasons for exploratory thoracotomy
      (ET), causes of unresectability of lung cancer, possibility for reducing numbers
      of ETs, and the influence of ET on survival. PATIENTS AND METHODS: Between 1990
      and 1999, 1808 patients with lung cancer were operated on. ET was performed in
      165 (9.1%) of these cases. In total, 131 ET patients were evaluable for analysis.
      The clinical stages were: three patients in stage IA, 28 in IB, one in IIA, 35 in
      IIB, 50 in IIIA, 10 in IIIB (all due to invasion of the mediastinum), and four
      patients in IV (three with ipsilateral pulmonary and one with solitary suprarenal
      metastasis). The control group for calculating survival difference consisted of
      130 consecutive non-operated patients with comparable characteristics (age, sex,
      clinical stage, performance status, histology and comorbidity) who were diagnosed
      during the period 1996-1998. RESULTS: The diagnostic procedure before ET
      comprised bronchoscopy in all patients, transthoracic needle biopsy in 13,
      cervical mediastinoscopy in nine, parasternal mediastinotomy in two and
      thoracoscopy in two, in all patients without proving unresectability. A CT scan
      was performed in 118 patients indicating resectability in 33%, doubtful
      resectability in 64% and unresectability in 3%. Clinical and surgical staging
      were equal in 3% of stage IIB patients, in 24% of stage IIIA, 100% of stage IIIB
      and 75% of patients in stage IV. The 30-day operative mortality was 4.6%. The
      reasons for ET were: diagnosis of preoperatively unverified tumor in one patient,
      necessity for pneumonectomy in the case of poor pulmonary function in 11
      patients, and unresectability in 119 (due to invasion of the mediastinum in 98
      patients, thoracic wall in three and vertebral body in one, and due to pleural
      metastases in 17 patients). ET could have been avoided in 15 (11%) patients. The
      median survival for both ET and control group patients was 11.1 months. The
      survival difference was not statistically significant (p = 0.420). CONCLUSION: ET
      could be partly avoided through a more accurate preoperative staging procedure.
      It does not appear possible to avoid ET in patients with limited pulmonary
      reserve precluding a resection larger than that predicted, nor to avoid ET as a
      consequence of intraoperative complications. Despite operative mortality, ET did
      not significantly influence the survival rate in the present study.

PMID- 16957980
TI  - A family outbreak of cryptosporidiosis: Probable nosocomial infection and person
      to-person transmission.
AB  - Cryptosporidium is an important cause of community gastroenteritis, usually
      associated with drinking contaminated water, visits to swimming pools or animal
      exposure. In immunocompetent patients, cryptosporidiosis is usually a self
      limiting disease but it can be devastating illness in immunocompromised persons.
      This report presents a family outbreak of cryptosporidiosis and describes a
      probable nosocomial infection with Cryptosporidium in one patient and subsequent
      spread of the parasite among members of his family. The index patient, a 72-year
      old man with hemiparesis after his third stroke, died after 28 days of persistent
      diarrhea. Control measures must be undertaken to prevent nosocomial transmission
      of cryptosporidial oocysts.

PMID- 16957981
TI  - [The representation of madness in William Shakespeare's characters].
AB  - Shakespeare is one of the great creators of human characters of the 16(th)
      century. Like for many of his contemporaries madness was a central topic of his
      work. The first part of this paper discusses the sociocultural environment and
      the semantic field of madness in the Elizabethan age, which forms the background
      for Shakespeare's characters. In the second part we try to analyze the clinical
      pictures of the fictive characters of Othello, Hamlet, Lear and Macbeth. While we
      find melancholy, delusions and hallucinations, other diseases such as
      schizophrenia are missing entirely. Schizophrenia only appears in the literature
      more than two hundred years later, in the beginning of modern age.

PMID- 16957983
TI  - The nucleoside diphosphate kinase from mimivirus: a peculiar affinity for
      deoxypyrimidine nucleotides.
AB  - The first viral Nucleoside Diphosphate Kinase was recently identified in the
      giant double-stranded DNA virus Acanthamoeba polyphag a Mimivirus (ApM). Here we
      report its expression and detailed biochemical characterization. NDK(apm)
      exhibits unique features such as a shorter Kpn-loop, a structural motif
      previously reported to be part of the active site and involved in oligomer
      formation. Enzymatic activity measurements on the recombinant NDK(apm) revealed
      its preferential affinity for deoxypyrimidine nucleotides. This property might
      represent an adaptation of NDK(apm) to the production of the limiting TTP
      deoxynucleotide required for the replication of the large A+T rich (72%) viral
      genome. The NDK(apm) might also assume a role in dUTP detoxification to
      compensate for the surprising absence of Mimivirus dUTPase (deoxyuridine
      triphosphate pyrophosphatase) an important enzyme conserved in most viruses.
      Although the phylogenetic analysis of NDK sequences sampled through organisms
      from the three domains of life is only partially informative, it favors an
      ancestral origin for NDK(apm) over a recent acquisition from a eukaryotic
      organism by horizontal gene transfer.

PMID- 16957984
TI  - Molecular interactions involving Escherichia coli nucleoside diphosphate kinase.
AB  - Nucleoside diphosphate kinase plays a distinctive metabolic role as the enzyme
      poised between the last reaction of deoxyribonucleoside triphosphate (dNTP)
      biosynthesis and the DNA polymerization apparatus. In bacteriophage T4 infection,
      NDP kinase is one of very few enzymes of host cell origin to participate in
      either dNTP synthesis or DNA replication. Yet NDP kinase forms specific contacts
      with phage-coded proteins of dNTP and DNA synthesis. This article summarizes work
      from our laboratory that identifies and characterizes these interactions. Despite
      these specific interactions, the enzyme appears to be dispensable, both for T4
      replication and for growth of the host, Escherichia coli, because site-specific
      disruption of ndk, the structural gene for NDP kinase, does not interfere with
      growth of the host cell and only partly inhibits phage replication. However, ndk
      disruption unbalances the dNTP pools and stimulates mutagenesis. We discuss our
      attempts to understand the basis for this enhanced mutagenesis.

PMID- 16957985
TI  - Regulatory roles for nm23/nucleoside diphosphate kinase-like enzymes in insulin
      secretion from the pancreatic islet beta cell.
AB  - Recent studies from multiple laboratories, including our own, provided fresh
      insights into the contributory roles for GTP-binding proteins (G-proteins) in
      glucose-stimulated insulin secretion (GSIS) from the islet beta cell. However,
      the precise mechanisms underlying the activation of this class of signaling
      proteins by insulin secretagogues remain only partially understood. We recently
      proposed that nm23/nucleoside diphosphate kinase (NDPK) catalyzes an alternate,
      non-receptor-dependent activation of islet endogenous G-proteins. In further
      support of this proposal, we report, herein, that overexpression of wild type
      (WT) nm23-H1 mutant in INS cells markedly potentiated GSIS. However, an inactive
      mutant of nm23-H1(H118F), which is deficient in histidine kinase and NDPK
      activities, was considerably less effective in potentiating GSIS from these
      cells, suggesting that both of these activities may be relevant for the
      potentiating effects of nm23-H1. Potential significance of these findings in
      relation to contributory roles for nm23/NDPK-like enzymes in the stimulus
      secretion coupling of GSIS is discussed.

PMID- 16957987
TI  - Evaluation of three-dimensional image registration methodologies for in vivo
      micro-computed tomography.
AB  - The advent of in vivo micro-computed tomography (micro-CT) provides a novel
      approach to measure the temporal adaptation of bone micro-architecture within an
      individual. Spatial alignment in the scanner between serial scans is challenging,
      but three-dimensional image registration can be used to superimpose the resulting
      image data, thus ensuring consistent regions of interest (ROI) for analysis.
      There have been several approaches to image registration developed, yet little is
      known about their application to high resolution micro-CT data. The purpose of
      this study was to explore combinations of three image registration similarity
      measures and three image interpolators, in addition to multi-resolution
      registration configurations, for assessment of computational efficiency and
      accuracy on both in vitro and in vivo micro-CT data. Accuracy measures were
      assessed by comparison with a gold-standard reference transform based on attached
      fiducial markers. It was concluded that a mutual information registration
      similarity measure with a linear image interpolator, applied at steps of
      increasing image resolution, provided the best compromise between accurate and
      efficient results. In vivo registration of tibial bone microstructure measured in
      an ovariectomized rat model provided consistent ROI thus demonstrating the
      usefulness of three-dimensional image registration for in vivo experimental and
      clinical micro-CT research. It is a technique that is poised to become commonly
      utilized for analysis of micro-CT data to diagnose and monitor efficacy of
      therapy in bone diseases.

PMID- 16957986
TI  - High energy phosphate transfer by NDPK B/Gbetagammacomplexes--an alternative
      signaling pathway involved in the regulation of basal cAMP production.
AB  - The activation of heterotrimeric G proteins induced by G protein coupled
      receptors (GPCR) is generally believed to occur by a GDP/GTP exchange at the G
      protein alpha -subunit. Nevertheless, nucleoside diphosphate kinase (NDPK) and
      the beta-subunit of G proteins (Gbeta) participate in G protein activation by
      phosphate transfer reactions leading to the formation of GTP from GDP. Recent
      work elucidated the role of these reactions. Apparently, the NDPK isoform B (NDPK
      B) forms a complex with Gbetagamma dimers in which NDPK B acts as a histidine
      kinase phosphorylating Gbeta at His266. Out of this high energetic phosphoamidate
      bond the phosphate can be transferred specifically onto GDP. The formed GTP binds
      to the G protein alpha-subunit and thus activates the respective G protein.
      Evidence is presented, that this process occurs independent of the classical GPCR
      induced GTP/GTP exchange und thus contributes, e.g. to the regulation of basal
      cAMP synthesis in cells.

PMID- 16957988
TI  - Inferences on a life distribution by sampling from the ages or the ages at death.
AB  - Consider a system where units having independent and identically distributed
      lifetimes enter according to a nonhomogeneous Poisson process. After the unit's
      life in the system, the unit departs the system. For a fixed system time, this
      paper relates the units' common underlying life distribution with the
      distribution of the ages of units in the system, the distribution for the system
      life of units that departed the system and the distribution for the system life
      of units that have recently departed the system. Results can be used to estimate
      the underlying life distribution or a truncated version of that distribution
      based on the ages and/or most recent ages at death in both one sample and two
      sample situations. Results include a complete characterization of the possible
      distribution of the ages of those units in the system, how to estimate the
      underlying life distribution from the most recent ages at death, and how to test
      for an underlying monotone failure rate function based on independent samples
      from the ages and most recent ages at death. Two sample inferences that involve a
      likelihood ratio ordering make use of the results in Dykstra et al. (1995, J Amer
      Statisc Assoc 90(431):1030-1040), which provides the maximum likelihood
      estimators and a likelihood ratio test when the two distributions satisfy a
      likelihood ratio ordering. For the ages of the active units and the ages at death
      among the departed units, limits for their distributions and strong limiting
      results for their empirical distributions will be provided.

PMID- 16957989
TI  - Mitochondrial DNA cleavage patterns distinguish independent origin of Chinese
      domestic geese and Western domestic geese.
AB  - It has generally been assumed, based on morphology, that Chinese domestic goose
      breeds were derived from the swan goose (Anser cygnoides) and that European and
      American breeds were derived from the graylag goose (Anser anser). To test the
      validity of this assumption, we investigated the mtDNA cleavage patterns of 16
      Chinese breeds and 2 European breeds as well as hybrids produced between a
      Chinese breed and a European breed. After 224 mtDNAs, isolated from the Chinese
      and European breeds, were digested by 19 restriction endonucleases, variations of
      the cleavage patterns were observed for four enzymes (EcoRV, HaeII, HincII, and
      KpnI). All Chinese breeds and their maternal hybrids except the Yili breed showed
      an identical haplotype, named haplotype I or the Chinese haplotype; the European
      breeds and the Yili breed showed another haplotype, named haplotype II or the
      western haplotype. None of the haplotype found in the Chinese type was detectable
      in the western type and vice versa. The two haplotypes were found to differ from
      each other at 8.0% of the sites surveyed and with a 0.72% sequence divergence.
      Using 2% substitution per million years calibrated from the genera Anser and
      Branta, the two domestic geese haplotypes were estimated to have diverged
      approximately 360,000 years ago, well outside the 3000-6000 years in domestic
      history. Our findings provide the first molecular genetic evidence to support the
      dual origin assumption of domestic geese in the world. Meanwhile, the four mtDNA
      restriction fragment length polymorphisms can be used as maternal genetic markers
      to distinguish the two types of domestic geese.

PMID- 16957990
TI  - Genetic variation in Hippophae rhamnoides ssp. sinensis (Elaeagnaceae) revealed
      by RAPD markers.
AB  - Hippophae rhamnoides ssp. sinensis is endemic to China, and it is a dioecious,
      outcrossing plant. Although many studies have been undertaken mainly on its
      agricultural, nutritional, medical, and ornamental value, little is known about
      its population genetics. This study uses random amplified polymorphic DNA to
      investigate the genetic diversity and population genetic structure of 13 natural
      populations of the subspecies sinensis. Fifteen primers amplified 107
      reproducible bands, with 95 (88.79%) being polymorphic. The gene diversity within
      population was 0.168, considerably lower than that of tree species and most
      perennial, outcrossing species, but higher than that of annual or short-lived,
      selfing species. The Gst value showed that 18.3% of the total genetic variation
      resided among populations, a little lower than that of outcrossing species. The
      present results are quite similar to those previously reported in another
      subspecies, H ssp. . rhamnoides rhamnoides. The low genetic differentiation among
      populations in ssp. sinensis may be attributed to the long-distance dispersal of
      seeds facilitated by birds, in addition to its characteristics of outcrossing,
      wind pollination, and widespread distribution. No association between genetic
      distance and geographical distribution was found. The population relationships
      revealed by the UPGMA dendrogram parallel this result, in that genetic distance
      did not increase with geographic separation. This pattern of population
      differentiation may imply the adaptation of ssp. s populations to the local
      environment, given that its habitats vary greatly across its distribution.

PMID- 16957991
TI  - Quantitative analysis of the conservation of the tertiary structure of protein
      segments.
AB  - The publication of the crystallographic structure of calmodulin protein has
      offered an example leading us to believe that it is possible for many protein
      sequence segments to exhibit multiple 3D structures referred to as multi
      structural segments. To this end, this paper presents statistical analysis of
      uniqueness of the 3D-structure of all possible protein sequence segments stored
      in the Protein Data Bank (PDB, Jan. of 2003, release 103) that occur at least
      twice and whose lengths are greater than 10 amino acids (AAs). We refined the set
      of segments by choosing only those that are not parts of longer segments, which
      resulted in 9297 segments called a sponge set. By adding 8197 signature segments,
      which occur uniquely in the PDB, into the sponge set we have generated a
      benchmark set. Statistical analysis of the sponge set demonstrates that rotating,
      missing and disarranging operations described in the text, result in the segments
      becoming multi-structural. It turns out that missing segments do not exhibit a
      change of shape in the 3D-structure of a multi-structural segment. We use the
      root mean square distance for unit vector sequence (URMSD) as an improved measure
      to describe the characteristics of hinge rotations, missing, and disarranging
      segments. We estimated the rate of occurrence for rotating and disarranging
      segments in the sponge set and divided it by the number of sequences in the
      benchmark set which is found to be less than 0.85%. Since two of the structure
      changing operations concern negligible number of segment and the third one is
      found not to have impact on the structure, we conclude that the 3D-structure of
      proteins is conserved statistically for more than 98% of the segments. At the
      same time, the remaining 2% of the sequences may pose problems for the sequence
      alignment based structure prediction methods.

PMID- 16957992
TI  - An evaluation of adult electrogastrography criteria in healthy children.
AB  - The current study examined whether electrogastrogram (EGG) recordings obtained
      from healthy children would be considered normal by standards established for
      adults and whether EGG patterns differ between children/adolescents and adults.
      Twenty-eight healthy children (54% females; ages 8-17 years; mean = 12.4 years)
      were evaluated and compared to 15 healthy adults evaluated previously. EGGs were
      recorded for 30 min in the fasting state and for 1 hr following a standard meal.
      For both pediatric and adult participants, there was a significant increase in
      both the dominant frequency and the dominant power from the pre- to the
      postprandial period (P < 0.001 for each). Using adult standards, the percentage
      normal slow waves was > 70% of the recording time in 96% of children in the
      fasting state and in 100% in the postprandial period. A postprandial power
      increase was seen in 89% of the children. In conclusion, our data indicate that
      American Motility Society (AMS) consensus adult criteria for a normal EGG are
      appropriate to apply to children and adolescents when utilizing methodology and
      meal challenge similar to those used to establish the adult norms.

PMID- 16957993
TI  - Roles of interstitial cells of Cajal in intestinal transit and exogenous
      electrical pacing.
AB  - The aims of this study were to investigate the role of interstitial cells of
      Cajal (ICCs) on small intestinal transit and its responses to exogenous pacing in
      W/W(v) mice. Eleven W/W(v) mice and their controls implanted with four pairs of
      gastrointestinal electrodes were used for testing the entrainment of slow waves.
      Another 20 W/W(v) mice and their controls equipped with a duodenal catheter and
      one pair of intestinal electrodes were used to test small intestinal transit
      represented by the geometric center (GC). Results were as follows. (1) The effect
      of pacing on slow wave frequency was sustained only in controls, and not in
      W/W(v) mice. (2) Both gastric and intestinal slow waves were completely entrained
      in controls and W/W(v) mice. Higher energy was required for pacing the stomach
      than the small intestine. (3) There was no significant difference in small
      intestinal transit between the controls and the W/W(v) mice (GC: 5.4 vs. 5.5).
      (4) Pacing showed no effects on small intestinal transit in either wild-type (GC:
      5.4 vs. 5.6) or W/W(v) mice (GC: 5.5 vs. 5.7). We conclude that myenteric ICCs
      may not play an important role in the regulation of small intestinal transit in
      conscious mice. Gastric and intestinal pacing can be achieved without ICCs.

PMID- 16957994
TI  - Remission of digestive insufficiency by islet transplantation to the pancreas.
AB  - Pancreatic digestive insufficiency is a common problem in both Type 1 and Type 2
      diabetes and remains a serious consequence of diabetes in developing countries.
      The problem is not corrected by supportive therapies including exogenous insulin
      injections. It is our hypothesis that digestive insufficiency may be corrected or
      diminished by the transplantation of islets to the pancreas, thereby supplying
      islet hormones directly to acinar tissue analogous to the normal pancreas.
      Diabetic rats received 1000 syngeneic islets and dogs received 7600 autologous
      islets per kilogram as a transplant to the pancreas. Blood glucose and amylase
      concentrations were normalized in islet recipients in contrast with controls
      receiving no islets or islets transplanted to the renal capsule. These results
      suggest that diabetic digestive insufficiency may be corrected by intrapancreatic
      islet transplantation.

PMID- 16957995
TI  - In vitro and in vivo protection of stellate cells from apoptosis by leptin.
AB  - Hepatic fibrogenesis is reduced in the absence of leptin. We hypothesized that
      leptin protects hepatic stellate cells (HSCs) from apoptosis and tested this in
      in vitro and in vivo systems. (i) Fas ligand (fas-L)-mediated apoptosis was
      induced in vitro in activated HSCs in the absence and presence of leptin. (ii)
      HSC apoptosis was also induced by UV irradiation in the absence and presence of
      leptin. (iii) Fas-L-mediated apoptosis was induced in vitro in HSCs from db/db
      mice in the absence and presence of leptin. (iv) Liver fibrosis was induced in wt
      and db/db mice. (v) Liver fibrosis was induced in wild-type mice with TAA, and
      mice received additional leptin or a control solution. HSC apoptosis was assessed
      by TUNEL staining. Western blot for alpha-SMA was used to determine differences
      in HSC activation. Results were as follows. (i) Fas-L induced significant
      apoptosis of HSC, and preincubation with leptin reduced this approximately
      threefold. (ii) Leptin provided no protection from UV-induced apoptosis. (iii)
      HSCs from db/db mice were not protected by leptin against fas-L-induced
      apoptosis. (iv) TAA-induced fibrosis was significantly less in db/db mice
      compared to wild type. (v) Wild-type mice receiving leptin had less apoptosis and
      more alpha-SMA than controls. We conclude that leptin protects HSC from in vitro
      and in vivo apoptosis. The antiapoptotic effect of leptin requires the long form
      of the leptin receptor and interacts with the apoptotic pathway proximal to
      mitochondrial activation.

PMID- 16957996
TI  - Increased risk of papillary thyroid cancer in celiac disease.
AB  - Patients with celiac disease have an increased rate of malignancies that are not
      limited to lymphomas. Thyroid carcinoma has not previously been associated with
      celiac disease. However, among a cohort of patients with celiac disease, we
      identified an increased risk of papillary carcinoma of the thyroid, standard
      morbidity ratio of 22.52 (95% confidence interval 14.90-34.04; P < .001),
      compared to United States national surveillance data. These patients were on a
      gluten-free diet. Only 1 had Hashimoto's thyroiditis, suggesting that mechanisms
      apart from autoimmune thyroiditis contribute to the increased risk of carcinoma
      of the thyroid in celiac disease.

PMID- 16957997
TI  - Analysis of randomized controlled trials on hepatopancreatic surgery.
AB  - The randomized controlled trial (RCT) is an important research method, providing
      the highest evidence and playing a pivotal role in the performance of evidence
      based medicine. However, RCTs on hepatopancreatic surgery have been performed
      less frequently than RCTs in other fields. Therefore, this review analyzes the
      characteristics of RCTs on hepatic and pancreatic surgery to propose a
      breakthrough. We retrieved studies performed via a MEDLINE search to identify
      prospective RCTs on hepatopancreatic surgery in the last decade. Eligible RCTs
      were analyzed using the following items: study design, publication year,
      geographical area, sample size, multicenter study, and impact factor. Studies
      comparing surgical technique or methods have composed the majority of the RCTs
      involving hepatectomy and pancreatectomy. About half of the RCTs on hepatectomy
      have been performed in East Asia, whereas most of the RCTs on pancreatectomy were
      undertaken in Western countries. The average sample number of RCT on hepatectomy
      is significantly smaller than those in other fields. Moreover, multicenter
      studies are less frequently performed on hepatectomy compared with
      pancreatectomy. Promoting the organization of multicenter studies would be the
      best way to increase the number and sample size of RCTs on hepatectomy. Adequate
      RCTs observing the Consolidated Standards of Reporting Trials statements are
      necessary to obtain reliable evidence.

PMID- 16957998
TI  - The effect of glutamine on pancreatic damage in TNBS-induced colitis.
AB  - Ulcerative colitis is a multifactorial inflammatory disease of the colon and
      rectum with an unknown etiology. The present study was undertaken to investigate
      the effect of glutamine administration on oxidative damage and apoptosis in 2,4,6
      trinitrobenzene sulfonic acid (TNBS)-induced colitis. Rats received 1 g/kg/day
      glutamine for intragastric gavage for 7 days before TNBS solution administration
      and 3 days following TNBS solution administration until sacrifice. Then colonic
      and pancreatic malondialdehyde (MDA) and glutathione (GSH) levels, and colonic
      caspase-3 activities of the sacrified rats were measured. TNBS-induced colitis
      caused significantly increased in the caspase-3 activity and colonic and
      pancreatic MDA levels and decreased colonic and pancreatic GSH levels compared to
      those in the sham group. Glutamine treatment was associated with decreased MDA
      levels and caspase-3 activity and increased GSH levels in the colinic and
      pancreatic tissue. Histopathological examination revealed that the colonic
      mucosal structure was preserved and pancreatic inflammation decreased in the
      glutamine-treated group. In conclusion, glutamine appears to have protective
      effects against TNBS-induced colonic and pancreatic damage. These results imply a
      reduction in mucosal damage due to anti-inflammatory and antiapoptotic effects of
      glutamine.

PMID- 16957999
TI  - Nocturnal hydration--an effective modality to reduce recurrent abdominal pain and
      recurrent pancreatitis in patients with adult-onset cystic fibrosis.
AB  - Recurrent abdominal pain and recurrent pancreatitis are common problems
      associated with some patients with cystic fibrosis (CF). There is no known
      effective method to prevent recurrent abdominal pain and recurrent pancreatitis
      in such patients. The objective of this study was to determine whether nocturnal
      hydration (NH) prevents recurrent abdominal pain and recurrent acute pancreatitis
      in patients with adult-onset CF. Adult CF patients who were referred to our
      Pancreatic Diseases Clinic for recurrent abdominal pain and pancreatitis were
      enrolled in the study. Each patient was encouraged to drink plenty of water
      during the night and established a 6-month diary (3 months before and 3 months
      after NH was initiated), recording the frequency and severity of their abdominal
      pain, the amount of pain medication taken, and the volume of their water intake.
      We also reviewed the number of doctor's clinic visits, emergency room visits, and
      hospitalizations for about 1 year before and 1 year after the initiation of the
      NH. The frequency and the severity of abdominal pain in this group of patients
      were significantly reduced. The amount of pain medication and the number of
      emergency room visits and hospitalizations for abdominal pain and acute
      pancreatitis were reduced. NH is a simple and cost-effective method to prevent
      recurrent abdominal pain and pancreatitis in patients with adult-onset CF.

PMID- 16958000
TI  - Leptin in the field of hepatic fibrosis: a pivotal or an incidental player?
AB  - Leptin is a 16-kDa nonglycosylated protein primarily secreted from the adipocytes
      of white fat; minor levels of regulated leptin expression also occurs at other
      sites such as placenta, skeletal muscle, the stomach fundus, and culture
      activated hepatic stellate cells (HSCs). Leptin is primarily involved in the
      regulation of food intake and body composition through a central feedback
      mechanism linking food ingestion, hypothalamus, and adipose tissue mass. In
      recent years, however, emerging evidence has suggested a critical role of leptin
      in hepatic inflammation and fibrogenesis and the influence of leptin on chronic
      liver disease has been an area of active research worldwide. In this review the
      data on the in vivo and in vitro actions of leptin on liver cells in experimental
      animal models of liver injury and the effects of leptin on human liver are
      discussed, with a focus on three distinct fields of chronic liver diseases:
      nonalcoholic steatohepatitis, alcoholic liver disease, chronic viral hepatitis,
      and, especially, hepatitis C.

PMID- 16958002
TI  - Social functioning in body dysmorphic disorder: assessment considerations.
AB  - Individuals with body dysmorphic disorder (BDD) have markedly poor social
      functioning; however, previous reports may underestimate impairment. Scoring on
      certain functioning measures such as the Social Adjustment Scale-Self Report (SAS
      SR) potentially excludes more severely ill individuals from some domains, thereby
      possibly underestimating functional impairment. To explore this issue, 73
      individuals with BDD who reported having no primary relationship (and were
      therefore excluded from scoring on the SAS-SR Primary Relationship domain) were
      compared to 58 individuals with BDD who had a primary relationship. Subjects
      without a primary relationship had significantly poorer global social adjustment
      on several measures. They also had poorer scores on the Global Assessment of
      Functioning Scale and greater severity of BDD and depressive symptoms at a trend
      level. These findings suggest that the SAS-SR may underestimate social
      impairment. This underestimation may pertain to other domains of functioning,
      other disorders, and certain other functioning and quality of life measures.

PMID- 16958001
TI  - Predictors of cirrhosis in Hispanic patients with nonalcoholic steatohepatitis.
AB  - It is estimated that 43% of patients with nonalcoholic steatohepatitis (NASH)
      will progress to liver fibrosis or cirrhosis. Although NASH is more common in
      Hispanics, most studies have been conducted on Caucasians, and there is scarce
      information regarding ethnic differences in this disease. The aim of this study
      was to identify the independent predictors of cirrhosis in Hispanic patients with
      NASH. A retrospective case-control study was conducted on 80 patients with biopsy
      proven NASH. Forty-two were Hispanic (study group) and 38 were Caucasians
      controlled for age and BMI (control group). Clinical, biochemical, and histologic
      features were analyzed for correlation with cirrhosis. There were no significant
      differences in demographic features between the two groups. In multivariate
      analysis, independent predictors of cirrhosis among Hispanic patients were age
      (OR, 1.07; 95% CI, 1.01-1.14) and AST/ALT ratio (OR, 10.56; 95% CI; 2.46-45.29),
      while independent predictors among non-Hispanic patients were age (OR, 1.085; 95%
      CI, 1.0-1.186), and diabetes mellitus (OR, 6.46; 95% CI, 1.19-35.07). In patients
      with NASH, predictors of cirrhosis varied according to ethnic background. Age was
      an independent predictor in both groups, however, AST/ALT ratio was found to be
      an independent predictor of cirrhosis only in Hispanic patients, and diabetes
      mellitus only in non-Hispanic patients.

PMID- 16958003
TI  - The impact of psychiatric comorbidity on general hospital length of stay.
AB  - Medical inpatients often suffer from comorbid psychiatric illness, which has been
      shown in previous studies to be associated with longer hospital stays. The
      present analysis used a large representative dataset to examine the impact of
      patient demographic and clinical characteristics on the relationship between
      psychiatric comorbidity and hospital length of stay. Analyses showed the
      existence of a psychiatric comorbidity predicted longer hospital stays for
      medical inpatients. However, in comparison to previous research, this effect was
      attenuated in this sample. Patients with mental disorders who were elderly, on
      Medicare, and those with schizophrenia or mood disorders were especially at risk
      for slightly longer lengths of stay.

PMID- 16958004
TI  - Cognitive mediators linking social support networks to colorectal cancer
      screening adherence.
AB  - This paper argues that normative considerations are more important than
      attitudinal factors in engaging colorectal cancer screening, and tests a model
      explaining how unique cultural expressions of social networks influence screening
      adherence. Structural equation modeling was used to understand colorectal cancer
      screening in a population-based sample of 341 Japanese Americans aged 50 and
      over. The model accounted for 25% of the variance in screening adherence.
      Adherence was most strongly associated with family/friend subjective norms about
      colorectal cancer screening use. Emotional family support, but not the size of
      the networks, was indirectly related to adherence via increased family/friend
      subjective norms, while emotional friend support was directly related to
      adherence. While usual source of care was directly associated with adherence,
      better provider-patient communication was directly and indirectly associated with
      adherence via increased perceived benefits. The findings of this study support
      strengthening informal support networks to enhance adherence among Japanese
      Americans at risk.

PMID- 16958005
TI  - Psychological adjustment following diagnosis and treatment of cancer: an
      examination of the moderating role of positive and negative emotional
      expressivity.
AB  - In support of cognitive processing models, emotional expression appears to reduce
      associations between intrusions and psychological distress. Past research has
      focused primarily on the role of the expression of negative emotion, or emotion
      in general, in cognitive processing and adjustment. In the present study, we
      examined the role of both positive and negative emotional expressivity on
      relations between intrusions and both distress and avoidance among 93 individuals
      diagnosed with and treated for cancer. We hypothesized stronger negative
      associations between intrusive thoughts and both distress and avoidance for those
      individuals lower in positive or negative expressivity. Results generally
      supported hypotheses with regard to relations of intrusions and distress in
      association with positive expressivity. Negative expressivity, however, moderated
      relations between intrusions and distress, but not intrusions and avoidance.
      These findings underscore the importance of examining the impact of individual
      differences in negative, as well as positive, emotional expression on cognitive
      processing and psychological adjustment.

PMID- 16958007
TI  - Genetics of cerebral cavernous angioma.
AB  - Cerebral cavernous malformations (CCM) are hamartomatous vascular anomalies
      characterized by densely packed, grossly enlarged immature capillaries without
      intervening neural tissue. Depending on their location and size (ranging from a
      few millimeters to several centimeters), the biologically dynamic lesions become
      symptomatic during the second to fourth decade of life. Clinical symptoms include
      recurrent headaches, seizures, intracranial hemorrhage, and stroke. There are
      sporadic and autosomal dominantly inherited forms of CCM. Causal mutations have
      been demonstrated in three genes, KRIT1, MGC4607, and PDCD10, but additional
      genes are likely to be discovered. These genes are therefore thought to play a
      role in angiogenesis. Their specific modes of actions, their contribution to and
      their likely penetrance in the genesis of CCM are the subject of current
      investigations. Genetic counseling is strongly advisable for patients with a
      positive family history and for seemingly sporadic cases with multiple lesions,
      and genetic testing should be considered on an individual basis. The
      identification of a mutation enables precise genetic testing of relatives. Given
      the 50 % a priori risk of autosomal dominant inheritance, the benefits of genetic
      testing are twofold: a positive test result in a presymptomatic carrier permits
      close neuroradiological surveillance and timely neurosurgical intervention; a
      negative test result relieves the proband of unwarranted anxiety and unnecessary
      medical supervision.

PMID- 16958008
TI  - Electrophysiological proof of diffusion-weighted imaging-derived depiction of the
      deep-seated pyramidal tract in human.
AB  - In the living human brain the pyramidal tract (PT) can be displayed with magnetic
      resonance diffusion-weighted imaging (DWI). Although this imaging technique is
      already being used for planning and performing neurosurgical procedures in the PT
      vicinity, there is a lack of verification of DWI accuracy in other areas outside
      the directly subcortical PT parts. Before definitive electrode placement into the
      subthalamic nucleus (STN) in patients with Parkinson disease (PD) for chronic
      stimulation, the stimulation effect on PD symptoms and the side-effects, namely
      PT activation at the level of the internal capsule (IC), are
      electrophysiologically tested. To analyze DWI accuracy by matching the
      stereotactic coordinates of the electrophysiologically proven IC position with
      these of the DWI-derived IC display, DWI was added to the routine MRI work-up in
      the stereotactic frame prior to functional surgery in 6 patients. In all of the
      10 displayed fiber tracts, concordant findings for imaging and macrostimulation
      were made. The authors proved for the first time that DWI correctly depicts the
      deep seated, principle motor pathways in the living human brain. Due to
      methodical limitations of this study the accuracy of the proven IC display is
      limited to 3 mm which has proven to be sufficient for the planning and
      performance of neurosurgical procedures in the vicinity of large fiber tracts.

PMID- 16958009
TI  - Spinal navigation: an accepted standard of care?
AB  - OBJECTIVE: In contrast to cranial neuro-navigation, which has been accepted as a
      routine intraoperative tool, there is still much debate about spinal navigation
      as an aid for the insertion of pedicle screws. Opinions range from "not useful at
      all" to "malpractice if not using it". The aim of our investigation was to obtain
      data about the availability of spinal navigation and compile a common opinion
      among German neurosurgeons about its usefulness. The current literature is
      reviewed. METHODS: We present the results of a survey of the Commission for
      Technical Standards of the German Neurosurgical Society about the use of
      intraoperative computerised spinal navigation. RESULTS: Of the 128 neurosurgical
      departments surveyed, 107 (84 %) responded. 57 (53 %) of the responders are
      equipped with a spinal navigation device, 12 (11 %) use a spinal navigation
      equipment together with other departments, and 38 (36 %) do not have spinal
      navigation. Of the departments not equipped with spinal navigation, 58 % would
      like to have it but 42 % would not. 52 (49 %) responders held the opinion that
      spinal navigation enhances safety when introducing pedicle screws; while 40 (37
      %) answered in the negative, and 15 (14 %) were not sure. Of the responders, 101
      (94 %) disagreed with the statement that spinal navigation should be mandatory
      for pedicle screw placement, 3 (3 %) agreed, and 3 (3 %) were not sure. Of the
      responders, 105 (98 %) rejected the statement that insertion of pedicle screws
      without navigation is medical malpractice, 1 (1 %) upheld the statement, and 1 (1
      %) was not sure. CONCLUSION: It is still not generally considered common practice
      to use spinal navigation as an aid for the implantation of pedicle screws. Most
      pedicle screws are still inserted conventionally. Although nearly 50 % of German
      neurosurgeons believe that spinal navigation could enhance safety when placing
      pedicle screws, they clearly reject efforts to make spinal navigation mandatory.
      With only one exception, the German neurosurgical community unanimously rejects
      the idea that placing pedicle screws without spinal navigation is medical
      malpractice.

PMID- 16958010
TI  - Virtual simulation of neuroendoscopic procedures: early clinical experience with
      ventricular lesions.
AB  - BACKGROUND: Virtual endoscopy (VE) is a new and promising imaging technology.
      Applied to neuroendoscopy it allows preoperative simulation of a procedure and
      evaluation of the individual intraventricular anatomy in selected cases. Along
      with neuronavigation and real time intraoperative imaging, VE is expected to
      improve the safety and efficacy of neuroendoscopic procedures. PATIENTS AND
      METHODS: Between April 2003 and February 2004 VE simulation was performed in 13
      randomly selected patients subjected to endoscopic procedures. Pathological
      entities included 4 cases with aqueduct stenosis, 4 with suprasellar arachnoid
      cysts, 2 tumors of the posterior third ventricle, 1 colloid cyst, 1 hyperplasia
      of the choroid plexus and 1 case with multiloculated hydrocephalus due to
      intraventricular septations. In 8 patients VE was accomplished preoperatively, in
      another 5 it was done after the operation, using data sets from neuronavigation
      imaging planning in 4 patients, and in one case using postoperative imaging
      studies. T (1)-weighted 3D image sets were acquired on a 1.5 T GE Genesis SIGNA
      MR scanner and VE reconstruction was performed using the General Electric
      Navigator software. The VE images were compared with the real images obtained
      during the endoscopic procedures and evaluated for their impact on the planning
      of the operative approach. RESULTS: VE implementation succeeded in all 13
      patients. Major neuroanatomic reference structures were easily recognizable in
      all cases. Membranous structures such as the thinned floor of the third ventricle
      or cyst walls were identifiable in only 46 % of the cases. In 6 cases (46 %) VE
      showed anatomical variants and details relevant for the endoscopic procedure that
      were not identified on conventional MR images. CONCLUSIONS: VE has proved to be
      an important adjunct to the preoperative planning of neuroendoscopic procedures
      and its routine application is suggested.

PMID- 16958011
TI  - Outcomes of surgical resection of large solitary hemangioblastomas of the
      craniocervical junction with limitations in preoperative angiographic
      intervention: report of three cases.
AB  - INTRODUCTION: Hemangioblastomas of the central nervous system may occur
      sporadically, or in association with von Hippel-Lindau (vHL) disease. The
      treatment of large solitary hemangioblastomas of the posterior cranial fossa
      mandates a combination of angiographic intervention and surgery. However, large
      tumors may derive their vascularity from major cerebellar vessels, which can make
      their embolization hazardous. AIM: To describe the surgical outcomes of three
      cases of large hemangioblastomas with compression of the medulla oblongata, where
      the potential for preoperative embolization was extremely limited. CASES: Three
      patients (all males; 68, 36 and 38 years) presented with a history of chronic
      headache and caudal cranial nerve deficiencies. Diagnostic imaging showed large
      vascular lesions (4 x 3, 4 x 5 and 5 x 5 cm) at the craniocervical junction,
      compressing the brainstem. There were no concomitant findings associated with vHL
      disease. TREATMENT: Staged treatment was administered. Preoperative embolization
      was attempted at first. One patient (68 yrs) showed a PICA occlusion and
      associated cerebellar infarction after embolization; embolization was deemed
      hazardous in the other two. In the second phase, the lesions were removed via a
      midline suboccipital approach with resection of the arch of altas. Complete
      removal was possible in all three cases. POSTOPERATIVE COURSE AND FOLLOW-UP: The
      caudal cranial nerve deficiencies deteriorated soon after surgery in all three
      patients. A tracheotomy was required in two patients, which was removed
      uneventfully during the rehabilitation phase. Ventriculo-peritoneal shunts were
      implanted in two patients. MRI follow-up three (1 case) and four years (2 cases)
      after surgery showed no relapse. The Karnofsky Index scores were 80, 70 and 90 in
      the three patients aged 68, 36 and 38, respectively. CONCLUSION: Total
      microneurosurgical removal of large hemangioblastomas at the craniocervical
      junction with limited preoperative embolization (associated with morbidity)
      should be seriously considered. Although the early outcome is not encouraging,
      the long-term outcomes seem favorable.

PMID- 16958012
TI  - Intradural-extramedullary cavernous hemangioma of the left motor root C7--case
      report and update of the literature.
AB  - OBJECTIVE: Intradural-extramedullary cavernomas of the spine are rare lesions
      with only 21 published cases to date. Due to their rareness and special
      characteristics diagnosis often is difficult. We report on an additional case of
      an intradural-extramedullary cavernoma of the spine. PATIENT: A 56-year-old male
      presented with left shoulder pain and acute onset of pain affecting the whole
      spinal column two weeks prior to admission. There were no motor deficits, but a
      hypesthesia corresponding to the right distal C8-dermatome. MRI revealed an
      intradural-extramedullary, expansive lesion at the level of C6 with a
      hyperintense appearance in both T (1)- and T (2)-weighted images. Neither a
      hemosiderin rim nor contrast enhancement was visible. RESULTS: During surgery a
      hematoma and a reddish, berry-like tumor adherent to the left motor root C7 were
      removed. There were no new neurological deficits, and shoulder and back pain
      resolved within a few weeks after surgery. Histopathologically a cavernous
      hemangioma was diagnosed. CONCLUSIONS: The patient's symptoms were caused both by
      direct nerve compression and by spinal hemorrhage, most likely spinal SAH. As
      there was no characteristic hemosiderin rim and due to the hyperintense
      appearance in T (1)- and T (2)-weighted MR scans, a radiological diagnosis of
      hemorrhage and classification of the lesion was difficult. Despite their
      rareness, in patients with signs of spontaneous, spinal SAH and/or nerve
      compression syndromes cavernous hemangiomas have to be considered as a potential
      cause.

PMID- 16958014
TI  - [biogf].

PMID- 16958013
TI  - Spontaneous cerebrospinal fluid rhinorrhea in untreated macroprolactinoma--an
      indication for primary surgical therapy.
AB  - BACKGROUND: Medical therapy is usually indicated as first-line treatment for
      prolactinomas. Surgery is generally reserved as second-line therapy if
      prolactinomas are non-responsive to dopamine agonists (DA) or DA therapy is not
      tolerated. Herein, we draw attention to the rare occurrence of spontaneous CSF
      rhinorrhea in prolactinomas requiring primary surgical therapy. Only 8 cases of
      confirmed prolactinomas with spontaneous rhinorrhea have been reported in the
      literature so far. CASE REPORTS: Two out of 267 surgical cases with pituitary
      adenomas presented with spontaneous rhinorrhea. Both patients harbored invasive
      prolactinomas. In both cases, the defect was exposed using a transsphenoidal
      procedure and was sealed with fascia lata. RESULTS: Urgent surgical repair of the
      leak prevented meningitis. In one case, a second operation was required due to
      recurrent rhinorrhea under postoperative dopamine-agonist therapy of the residual
      tumor. The clinical course was otherwise uncomplicated. CONCLUSION: Certain
      clinical settings still require primary surgical therapy of prolactinomas.
      Spontaneous rhinorrhea caused by invasive macroprolactinomas represents a
      mandatory indication for initial surgery. Early detection and surgical repair of
      a CSF leak is crucial for a favorable clinical outcome.

PMID- 16958015
TI  - [Osteochondritis dissecans of the knee joint].
AB  - Osteochondritis dissecans is a disorder with a prevalence of 0.01 to 0.06 %. Men
      between 16 and 36 years of age are most commonly affected by it. In the western
      hemisphere, the knee is affected by this progressive disorder in 75 % of the
      cases, specifically the medial femoral condyle (70 - 80 %). The etiology is
      uncertain, although genetic defects, micro-trauma, ossification disorders and
      ischemia have been implicated. Pathogenetically, Osteochondritis dissecans is
      classified in four stages, whereas in stage one, there is merely a subchondrial
      edema. Without therapy this could lead to stage 4, with a free osteochondral
      joint fragment. Treatment is analogous with the stage of the disorder. Whereas
      conservative treatment may yield full recovery during stage 1, starting in stage
      2, invasive treatment should be considered. When the cartilage surface remains
      intact retrograde procedures are indicated. If the cartilage is injured
      anterograde therapies, like the chondral or osteochondral transplantation, should
      be used.

PMID- 16958016
TI  - [Tissue helminthoses].
AB  - Helminthic infections affecting host organs/tissues belong to the most important
      parasitic infections. In the Czech Republic, an increase in the travelers to and
      immigrants from endemic countries has been noted. Except for larval toxocarosis,
      however, the total number of patients with schistosomiasis, hydatid disease,
      cysticercosis and filariases does not exceed 15 cases per year till present. It
      remains to be solved whether this situation reflects manners of a Czech tourist
      in endemic areas or the diseases are neglected during routine practice. The
      presented paper, therefore, focuses on some diagnostically important features
      accompanying helminthic infections. And, clinical symptoms and signs of the
      infections are analysed in relation to the patient history and laboratory
      findings.

PMID- 16958017
TI  - [Helminth migration in the host].
AB  - Helminths belong to important human pathogens in tropical and subtropical
      countries. They have simple one-host life cycles or they use several hosts for
      their development. There are two main entry points for human helminths: the skin
      and the oral cavity. Skin penetration is followed by tissue migration of helminth
      stages towards target organs. Also some perorally acquired helminths migrate
      throughout the human body and then (a) they return to and mature in the intestine
      or (b) they search for specific final location in other (extraintestinal)
      tissues/organs. Particular developmental stages having different migration
      routes, and different roles of human beings as final, intermediate and paratenic
      hosts are briefly mentioned.

PMID- 16958018
TI  - [Pathology of urogenital schistosomiasis].
AB  - The authors submit the case history of their patient presenting with chronic
      cystitis, consequence of an infestation with the fluke Schistosoma haematobium.
      They also present the most frequent morphological forms of urogenital
      schistosomiasis, its complications and the possibilities of pathological
      differential diagnosis, based on literary data (including information from
      electronic data bases) on the pathomorphology and, more particularly, the
      histopathology of urogenital schistosomiasis. Among the general histopathological
      changes we see lesions that correspond to an active chronic infection with a
      chiefly granulomatous reaction. Calcification, pseudotumorous polypoid
      formations, ulcerations, obliterating fibrous lesions, epithelial transformations
      such as hyperplasia, metaplasia and dysplasia follow later. These changes are
      followed at the various sites by diverse clinical and morphological complications
      posthaemorrhagic anaemia, adhesions, serious obstructions of urogenital openings
      and its consequences and, finally, an increased risk of pavement-cell carcinoma
      of the bladder. For all the above-mentioned reasons we should include the
      possibility of urogenital schistosomiasis into the large group of clinical and
      pathological aspects of differential diagnosis, when considering the etiology and
      treatment of inflammatory and tumorous lesions of the urogenital tract.

PMID- 16958019
TI  - [Pathogenesis of severe sepsis--from macrocirculation to mitochondria].
AB  - Severe sepsis is at present serious medical and social problem. In contrast to
      many other diseases its incidence shows an upward tendency and so does mortality
      due to sepsis. From the point of view of pathogenesis the cause of this complaint
      is a disturbed response to infection. The basis of this disruption is either a
      huge local inflammation that goes hand in hand with the penetration of
      proinflammatory cytokines into systemic circulation or an excessive
      proinflammatory systemic response. In the first instance the consequence is a
      systemic proinflammatory response accompanied by a disruption of
      macrocirculation, later also of microcirculation and finally mitochondrial
      failure. These mechanisms are responsible for the gradual failure of distant
      organs. In the second instance the consequence is a deactivation of systemic and
      local immunocompetent cells accompanied by the risk of uncontrolled proliferation
      of microorganisms. Affected are organs with a disturbed antimicrobial barrier,
      especially the lungs du ring mechanical ventilation, the bloodstream or the
      urinary system during catheterization. A large group of selectively acting
      preparations has been clinically tested in the management of this disorder, but
      only very few of these preparations were efficacious. We may postulate that the
      great diversity of the investigated population of patients was responsible for
      this lack of success.

PMID- 16958020
TI  - [Detection and significance of biofilm formation in yeasts isolated from
      hemocultures].
AB  - BACKGROUND: Yeasts of the genus Candida are important opportunistic pathogens
      responsible for severe bloodstream infections in immunocompromised patients. An
      important virulence factor that allows them to colonize plastic implants and to
      survive in the blood is their ability to form biofilm. The purpose of the study
      was to assess, how frequently this virulence factor occurred in yeasts of the
      genus Candida isolated from blood cultures. MATERIALS AND METHODS: Cultures of
      the various strains in wells of microtitre plates were used to demonstrate the
      presence of biofilms. In total, we tested 72 isolates of yeasts of the genus
      Candida from the blood culture: C. albicans (33), C. parapsilosis (19), C.
      tropicalis (11), C. glabrata (4), C. krusei (3), C. lipolytica (1) and C.
      lusitaniae (1). RESULTS: The ability to form biofilm was demonstrated in 26
      strains. The largest number of biofilm-positive strains was found in C.
      parapsilosis (13) and C. tropicalis (7). The formation of biofilms was far less
      frequent in the strains of C. albicans (4). The formation of biofilms was also
      demonstrated in C. krusei (2) and C. glabrata (1). CONCLUSION: The increasing
      frequency of fungal bloodstream infections is due to the increasing use of
      catheters and implants. The biofilm formation in these yeasts is the chief factor
      of virulence promoting such infections. The demonstration of biofilm formation in
      an isolated strain is indicative of the probable existence of a biofilm focus and
      of possible difficulties during antimycotic therapy.

PMID- 16958021
TI  - [Growth and detection of aerobic bacterial pathogens in BacT/Alert FA, BacT/Alert
      SA, Bactec Plus Aerobic/F and Bactec Standard Aerobic/F].
AB  - The article compares the ability of detection and detection times (TTD) of
      aerobic bacteria in the BacT/Alert FA, BacT/Alert SA, Bactec Plus Aerobic/F and
      Bactec Standard Aerobic/F bottles. Compared bottles were inoculated at the same
      time with the identical suspension of bacterial strain. All bottles detected
      bacterial pathogens even in the case of very low number of inoculated bacteria.
      The differences of TTD were detected between the bottles of compared
      hemocultivation systems. Bactec Plus Aerobic/F system is faster in the detection
      of the members of family Enterobacteriaceae at 1-3 hours, BacT/Aert FA system is
      faster in the detection of coagulase-negative staphylococci. Most difference was
      detected at Pseudomanas stutzeri, where the detection in BacT/Alert FA bottles
      was at 15 hours faster in opposite of Bactec Plus Aerobic/F bottles. In the
      bottles without sorbent Staphylococcus aureus and Streptococcus sanqui were
      detected faster in the system Bactec Standard Aerobic/F. The bottles BacT/Alert
      SA detected faster skin corynebacteria. Detected differences have not a practical
      importance for the blood stream infection diagnostics.

PMID- 16958022
TI  - [Ocular sparganosis in the Czech Republic--a case report].
AB  - The authors report a case of 14-year-old boy presented to the Ophthalmologic
      Department of University Hospital in Olomouc with the diagnosis af acute anterior
      uveitis. A living parasite has been detected in the anterior chamber in a slit
      lamp examination. The vitreous and retina remained uninvolved. The acute
      iridocyclitis associated with parasitic infection is a very rare cause of
      anterior uveitis in Central Europe. The patient underwent surgical removal of the
      parasite via paracentesis. The inflammation resolved under the treatment with
      atropine and dexamethasone drops within a few days. Histopathological examination
      revealed the parasite as a young larval stage of tapeworm from family
      Pseudophyllidea (sparganum). Based on the analysis of development cycles of
      different types of tapeworms and according the literature data on tapeworms found
      in the Czech Republic genus Spirometra seemed to be the most plausible cause of
      the patient's disease. As the most probable source of viable parasites authors
      suspect swallowed water containing tiny infected crustaceans in the dam near the
      town Olomouc in Moravia.

PMID- 16958023
TI  - [Schistosomiasis cases at the Teaching Hospital Kralovske Vinohrady in Prague].
AB  - In our paper we present the diagnosis of schistosomiasis at the Teaching Hospital
      Kralovske Vinohrady in Prague. This helminthiasis is imported to the Czech
      Republic by tourists and foreigners from subtropical and tropical regions of
      Africa, Asia, Central and South America. An unrecognized and thus untreated
      infection may have serious, even fatal consequences for the patient. In the
      period 2003 to 2005 in our parasitological investigations we have seen two cases
      infested with two fluke species imported from Africa. We submit the case
      histories of these patients.

PMID- 16958024
TI  - Intussusception: a rare cause of abdominal pain in pregnancy.
AB  - A 34-year-old woman presented at 19 weeks in her third pregnancy with abdominal
      pain and hyperemesis. This was her third admission during the pregnancy for
      similar complaints. A few days after admission an exacerbation in her pain was
      noted, in particular on eating or lying down, and a firm and mobile epigastric
      mass could be palpated separate from her uterus. The differential diagnosis was a
      hernia or a degenerating pedunculated fibroid. Sonography revealed a mass
      separate from the uterus with an appearance consistent with intussusception.
      Magnetic resonance imaging confirmed the diagnosis. A limited right hemicolectomy
      was performed. The final diagnosis was adenocarcinoma of the colon. It is
      difficult to diagnose intussusception during pregnancy. The presenting symptoms
      of nausea, vomiting, abdominal pain and constipation are common in pregnancy and
      the displacement of the bowel by the gravid uterus hampers examination.
      Intussusception is very rare in adults and generally it is associated with
      tumors. Preoperative diagnosis is difficult but possible with accurate imaging.

PMID- 16958025
TI  - The National Cancer Institute's Special Populations Networks for cancer
      awareness, research, and training.

PMID- 16958026
TI  - Redes En Accion. Increasing Hispanic participation in cancer research, training,
      and awareness.
AB  - Hispanics are affected by many health care disparities. The National Cancer
      Institute (NCI), through its Special Populations Branch, is supporting networking
      and capacity-building activities designed to increase Hispanic participation and
      leadership in cancer research. Redes En Accion established a national network of
      cancer research centers, community-based organizations, and federal partners to
      facilitate opportunities for junior Hispanic scientists to participate in
      training and research projects on cancer control. Since 2000, Redes En Accion has
      established a network of more than 1800 Hispanic leaders involved in cancer
      research and education. The project has sustained 131 training positions and
      submitted 29 pilot projects to NCI for review, with 16 awards for a total of
      $800,000, plus an additional $8.8 million in competing grant funding based on
      pilot study results to date. Independent research has leveraged an additional $32
      million in non-Redes funding, and together the national and regional network
      sites have participated in more than 1400 community and professional awareness
      events. In addition, the program conducted extensive national survey research
      that provided the basis for the Redes En Accion Latino Cancer Report, a national
      agenda on Hispanic cancer issues. Redes En Accion has increased participation in
      cancer control research, training, and awareness among Hispanic scientists and
      within Hispanic communities. Cancer 2006. (c) 2006 American Cancer Society.

PMID- 16958028
TI  - Autistic-spectrum disorders in Down syndrome: further delineation and distinction
      from other behavioral abnormalities.
AB  - The present study extends our previous work characterizing the behavioral
      features of autistic-spectrum disorder (ASD) in Down syndrome (DS) using the
      Aberrant Behavior Checklist (ABC) and Autism Behavior Checklist (AutBehav). We
      examined which specific behaviors distinguished the behavioral phenotype of DS +
      ASD from other aberrant behavior disorders in DS, by determining the relative
      contribution of ABC and AutBehav subscales and items to the diagnosis of ASD. A
      total of 127 subjects (aged 2-24 years; mean age: 8.4 years; approximately 70%
      male), comprising: a cohort of 64 children and adolescents with DS and co-morbid
      ASD (DS + ASD), 19 with DS and stereotypic movement disorder (DS + SMD), 18 with
      DS and disruptive behaviors (DS + DB), and 26 with DS and no co-morbid behavior
      disorders (DS + none) were examined using the aforementioned measures of aberrant
      behavior. We found that subjects with DS + ASD showed the most severe aberrant
      behavior, especially stereotypy compared to DS + none and lethargy/social
      withdrawal and relating problems compared to DS + SMD. Specifically, relatively
      simple stereotypic behavior differentiated DS + ASD from DS + DB, whereas
      odd/bizarre stereotypic and anxious behavior characterized DS + ASD relative to
      DS + SMD and DS + none. Additionally, in a subset of subjects with DS + ASD and
      anxiety, social withdrawal was particularly pronounced. Overall, our findings
      indicate that a diagnosis of DS + ASD represents a distinctive set of aberrant
      behaviors marked by characteristic odd/bizarre stereotypic behavior, anxiety, and
      social withdrawal.

PMID- 16958027
TI  - Family-based association study of TPH1 and TPH2 polymorphisms in autism.
AB  - The TPH1 and TPH2 genes encode the rate-limiting enzymes that control serotonin
      biosynthesis, and serotonin is clearly altered in autism. In the current study,
      eight SNPs in the TPH1 gene region and eight SNPs within the TPH2 gene were
      examined by family-based association tests in a large cohort of 352 families with
      autism and in clinically defined subsets of these families with either severe
      obsessive-compulsive behaviors (sOCB) or self-stimulatory behaviors (SSB). We
      found no evidence for association between autism and single SNPs or haplotypes of
      the TPH1 and TPH2 genes in the cohort of all families or in the sOCB and SSB
      subsets. In particular, we failed to replicate the association between autism and
      variants of the TPH2 gene, rs4341581 (TRANSMIT P = 1; PDT P = 0.323; FBAT P =
      0.446) and rs11179000 (TRANSMIT P = 0.174; PDT P = 0.293; FBAT P = 0.374).
      Furthermore, no evidence for linkage was observed between autism and SNPs in the
      TPH1 and TPH2 genes (although linkage at the TPH2 locus was observed in the SSB
      subset). Thus, it appears unlikely that the TPH1 and TPH2 genes play a
      significant role in the susceptibility to autism or to autism endophenotypes
      including sOCB and SSB.

PMID- 16958029
TI  - Association of the human kainate receptor GluR7 gene (GRIK3) with recurrent major
      depressive disorder.
AB  - The etiology of mood disorders remains elusive, despite our increasing
      understanding of the neurotransmitter systems and brain regions that are
      involved. We performed a large family-based association study to test if the
      human kainate receptor GluR7 gene (GRIK3) is associated with bipolar disorder
      (BP) or recurrent major depressive disorder (R-MDD). One hundred fifty-three
      multiplex BP families from the National Institute of Mental Health (NIMH)
      Genetics Initiative on Bipolar Disorder were analyzed with the transmission
      disequilibrium test (TDT). We detected a significant linkage disequilibrium (LD)
      indicated by preferential maternal transmission of the GluR7 S310 allele to R-MDD
      patients (P = 0.012), but not to bipolar I disorder (BPI) patients (P = 1.00). We
      performed a second independent study by applying the TDT in 81 parent-offspring
      triads from families that inherit recurrent early-onset major depressive disorder
      (RE-MDD). The results from this second study showed only a suggestive maternal
      association (P = 0.068). Our findings imply that the GluR7 gene is a
      susceptibility factor in R-MDD and that the glutamatergic receptor system plays a
      critical role in the disease etiology.

PMID- 16958030
TI  - The genomic era and perceptions of psychotic disorders: genetic risk estimation,
      associations with reproductive decisions and views about predictive testing.
AB  - As a result of publicity surrounding genetic advances, increasing public
      awareness of a genetic role in major mental illness may be contributing to a
      "geneticization" of these illnesses. Geneticization could lead to oversimplified
      ideas about genetic risk, producing significant social consequences. We sought to
      investigate perceptions of genetic risk, associated effects on reproductive
      decisions and attitudes towards genetic testing amongst unaffected relatives of
      individuals with psychosis. A web-based survey design was used, which all
      visitors to a psychosis support/information website had the option to complete.
      Responders were representative of website visitors, and the study design
      facilitated collection of a large dataset, although the response rate was low.
      Over-estimating risk was associated with reproductive decisions favoring fewer
      children, and more positive attitudes towards genetic testing. Facilitating
      accurate risk perception through genetic counseling could significantly impact
      reproductive decisions, and the appropriate use of genetic tests in the future.

PMID- 16958031
TI  - Recurrence risk to offspring in extended multiplex schizophrenia pedigrees from a
      Pacific Island isolate.
AB  - Genetic transmission plays a major role in the pathogenesis of schizophrenia.
      Family, twin, and adoption studies have consistently shown that risks in
      relatives are many times greater than the general population risk of
      approximately 1%. McGue, Gottesman, and Rao (1983; Am J Hum Genet 35:1161-1178)
      calculated risk estimates of 12.8% for offspring and 3.5% for nieces/nephews of
      schizophrenia patients based on a large data set of Western European families.
      The present study evaluated corresponding risk levels in Palau, an isolated
      population in Micronesia where the prevalence of narrowly (broadly) defined
      schizophrenia is 1.99% (2.67%) and cases cluster in extended pedigrees, 20 of
      which contain 80% of affected individuals. We hypothesized that offspring in
      these extended families would have a higher risk for schizophrenia than offspring
      in smaller schizophrenia pedigrees from more genetically heterogeneous
      populations. RDC diagnostic data based on complete ascertainment of cases and
      their families covering the past two generations were used to quantify empirical
      recurrence risks in the offspring and nieces/nephews of Palauan schizophrenia
      patients. Risks to 1st- and 2nd-degree offspring were approximately double the
      rates found in the smaller Western European families: 23.4% in the offspring of
      an affected parent, 6.4% in offspring with one affected aunt/uncle, and 15.0% in
      offspring with two or more affected aunts/uncles. Recurrence rates in offspring
      of an affected parent were 1.6 times higher in males (27.9%) than in females
      (17.7%). The high risk levels we found in Palauan offspring reflect the elevated
      population prevalence, strong familial aggregation, and multi-lineal transmission
      pattern of schizophrenia in Palau.

PMID- 16958032
TI  - Evidence of linkage to psychosis on chromosome 5q33-34 in pedigrees ascertained
      for bipolar disorder.
AB  - It is hypothesized that the presence of psychotic features may define a subtype
      of bipolar disorder that is more homogeneous in its genetic predisposition than
      bipolar disorder as a whole. We used psychosis as an alternative phenotype
      definition in a re-analysis of the NIMH Bipolar Genetics Initiative data sets. In
      this analysis we selected only those families in which at least two members were
      diagnosed with bipolar disorder type 1 with psychotic features. This analysis
      identified a linkage signal on chromosome 5q33-q34, a region previously
      implicated in independent linkage studies of schizophrenia and of psychosis,
      broadly defined. This finding is consistent with the hypothesis that
      susceptibility to psychosis may characterize at least a subtype of bipolar
      disorder.

PMID- 16958034
TI  - Developments in neuroacanthocytosis: expanding the spectrum of choreatic
      syndromes.
AB  - As with other neurodegenerative disorders, research into the group of diseases
      known under the umbrella term of "neuroacanthocytosis" has greatly benefited from
      the identification of causative genes. The distinct and unifying aspect of these
      disorders is the presence of thorny deformations of circulating erythrocytes.
      This may be due to abnormal properties of red cell membranes, which could lead to
      insights into mechanisms of neurodegeneration. Research approaches in this field,
      in addition to examining functions and protein interactions of the affected
      proteins with particular respect to neurons, have also drawn upon the expertise
      of hematologists and red cell membrane biologists. In this article, recent
      developments in the field are presented.

PMID- 16958033
TI  - The role of RELN in lissencephaly and neuropsychiatric disease.
AB  - Reelin is an extracellular matrix-associated protein important in the regulation
      of neuronal migration during cerebral cortical development. Point mutations in
      the RELN gene have been shown to cause an autosomal recessive human brain
      malformation termed lissencephaly with cerebellar hypoplasia (LCH). Recent work
      has raised the possibility that reelin may also play a pathogenic role in other
      neuropsychiatric disorders. We sought, therefore, to define more precisely the
      phenotype of RELN gene disruption. To do this, we performed a clinical,
      radiological, and molecular study of a family in whom multiple individuals carry
      a chromosomal inversion that disrupts the RELN locus. A 6-year-old girl
      homozygous for the pericentric inversion 46,XX,inv7(p11.2q22) demonstrated the
      same clinical features that have been previously described in association with
      RELN point mutations. The girl's brain magnetic resonance imaging (MRI) findings,
      including pachygyria and severe cerebellar hypoplasia, were identical to those
      seen with RELN point mutations. Fluorescence in situ hybridization confirmed that
      one of the breakpoints of this inversion mapped to within the RELN gene, and
      Western blotting revealed an absence of detectable serum reelin protein. Several
      relatives who were heterozygous for this inversion were neurologically normal and
      had no signs of psychotic illness. Our findings demonstrate the distinctive
      phenotype of LCH, which is easily distinguishable from other forms of
      lissencephaly. Although RELN appears to be critical for normal cerebral and
      cerebellar development, its role, if any, in the pathogenesis of psychiatric
      disorders remains unclear.

PMID- 16958035
TI  - Schizophrenia is not associated with the functional candidate gene ERBB3: results
      from a case-control study.
AB  - Increasing evidence has supported the hypothesis of a neurodevelopmental
      component in the etiology of schizophrenia. Recently, several independent
      microarray gene expression studies have revealed downregulated expression of
      myelin-related genes in the postmortem brains of schizophrenia patients. Complete
      myelination of the cortex has been observed to occur in late adolescence and
      early adulthood, which is typically the age of onset of schizophrenia. ERBB3 is a
      gene which has not only been found to be downregulated in schizophrenia
      simultaneously in three microarray studies, but also is a strong candidate
      because of its potential role in neurodevelopment as a receptor of NRG1.
      Therefore, we performed association analysis of seven nonsynonymous SNPs in this
      gene. Two SNPs in ERBB3 (rs773123 and rs2271188) were polymorphic in our samples,
      neither of which showed significant evidence of association with the illness (P =
      0.639 and 0.561, respectively). Because replication across such studies is
      notoriously difficult, the microarray evidence implicating ERBB3 still strongly
      supports some role of this gene in schizophrenia. However, our failure to find
      genetic association suggests that the differential expression of ERBB3 in
      schizophrenia may be environmentally driven, or involve cis- or trans-acting
      genetic factors beyond the boundaries of the gene itself.

PMID- 16958036
TI  - The serotonin receptor HTR1B: gene polymorphisms in attention deficit
      hyperactivity disorder.
AB  - Serotonin plays an essential role in cognition, locomotor activity, and the
      regulation of sleep, pain, mood, and aggression. Polymorphisms of the HTR1B gene
      have been implicated in a variety of psychiatric disorders including attention
      deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD).
      The objectives of this study were to: (i) expand our original investigation of
      the relationship between the HTR1B receptor gene and attention
      deficit/hyperactivity and; (ii) to investigate a possible association of
      obsessive behaviors/perfectionism and the HTR1B gene in a sample of 203 families
      with an ADHD proband. Six single nucleotide polymorphisms (SNPs) of the HTR1B
      receptor gene were genotyped using standard methods. Evidence for an association
      between the HTR1B gene and ADHD as a qualitative diagnosis, or the inattentive
      and hyperactive-impulsive quantitative traits was not supported by either TDT
      single marker analysis or haplotype analysis. In addition we did not find
      evidence to suggest an association between HTR1B and perfectionism in this sample
      of ADHD families.

PMID- 16958037
TI  - Further evidence of MAO-A gene variants associated with bipolar disorder.
AB  - The aim of this study was to investigate MAOA gene variants in bipolar disorder
      by using a family-based association approach. The first sample included 331
      nuclear families from Western and Central Canada with at least 1 offspring
      affected with bipolar disorder comprising a total of 1,044 individuals. All
      subjects were genotyped for MAOA-941T > G and -uVNTR gene variants using PCR
      techniques. Haplotype TDT was statistically significant (LRS = 12.17; df = 3; P =
      0.0068; permutation global significance = 0.00098), with the T-4 haplotype
      significantly associated with bipolar disorder (OR = 1.63, 95% CI = 1.11-2.37).
      Single marker analysis evidenced a borderline association for MAOA-941T > G (P =
      0.04), but not for the uVNTR. Pooling the Canadian sample with a second
      previously reported Italian sample genotyped for the uVNTR variant, negative
      results were obtained as well. No different results were detected when analyzing
      female subjects separately. In conclusion, our family-based association study
      gives mild but further support of the involvement of MAOA variants in bipolar
      disorder.

PMID- 16958038
TI  - Serotonin genes and attention deficit/hyperactivity disorder in a Brazilian
      sample: preferential transmission of the HTR2A 452His allele to affected boys.
AB  - Attention-deficit hyperactivity disorder (ADHD) is one of the most common
      psychiatric disorders of childhood. The role of genetic factors in its etiology
      is strongly supported by family, adoption, and twin studies. Low serotonin
      activity has been associated in both animal and human studies with measures of
      impulsivity, aggression, and disinhibited behaviors, which make genes from the
      serotonin system reasonable candidates for ADHD susceptibility. In the present
      study, we investigated a polymorphism in the promoter region of the serotonin
      transporter (SLC6A4) and two polymorphisms (-1438 A > G and His452Tyr) in the
      serotonin 5-HTR2A receptor gene using family based association analyses in a
      sample of 243 Brazilian ADHD children and adolescents and their parents. No
      linkage disequilibrium between the two HTR2A polymorphisms was detected in this
      sample (P = 0.76). Considering several evidences from animal models for sexual
      dimorphism in serotonin genes expression, analyses were performed separately for
      the whole sample and for male probands. No evidences for biased transmissions of
      both HTR2A -1438 A > G and SLC6A4 polymorphisms to ADHD youths were observed.
      Preferential transmission of the HTR2A His452 allele was observed only in
      families with affected boys (P = 0.04). Our results suggest that findings from
      ADHD association studies for serotonin genes might be understood in the context
      of a gender effect, which may help to explain conflicting results in these
      association studies.

PMID- 16958039
TI  - Serotonin transporter mRNA levels are associated with the methylation of an
      upstream CpG island.
AB  - The serotonin reuptake transporter (5HTT) is thought to be the principal
      regulator of serotonergic activity and epigenetic effects at this locus are
      thought to be important moderators of vulnerability to neuropsychiatric illness.
      In attempt to understand the basis of this regulation, several gene polymorphisms
      that affect 5HTT mRNA levels have been described. But to date, no clear mechanism
      linking these polymorphisms to vulnerability to epigenetic effects have been
      described. In this communication, we describe a CpG island in the 5' region of
      the 5HTT gene that contains an alternative exon 1 and possible promoter for 5HTT.
      We then confirm the existence of this transcript and ascertain the methylation
      status of this CpG island in 49 lymphoblast cell lines and analyze the
      relationship between methylation and 5HTT mRNA levels. We demonstrate that
      methylation at this CpG island is associated with decreased levels of 5HTT mRNA,
      but that this effect is evident only when 5HTTLPR genotype is taken into account.
      We suggest that these findings have significant implications for the
      understanding of the role of this locus in behavioral illness.

PMID- 16958040
TI  - Allelic association of a truncation mutation of the KCNMB3 gene with idiopathic
      generalized epilepsy.
AB  - The gene encoding the beta3-subunit regulatory subunit (KCNMB3) of large
      conductance calcium-sensitive potassium (BK) channels represents a positional and
      functional candidate gene for idiopathic generalized epilepsy (IGE). A single
      base pair deletion in exon 4 of KCNMB3 (delA750) alters/truncates the terminal 21
      amino acids of the 3-subunit and affects channel inactivation of the beta3b
      isoform. The present association study tested whether the KCNMB3 delA750 mutation
      confers susceptibility to common IGE syndromes. In total, 592 unrelated German
      IGE patients and 462 healthy population controls were genotyped for the delA750
      truncation mutation. The frequency of the delA750 mutation was significantly
      increased in the IGE patients (7.9%) compared to that in the controls (5.5%; P =
      0.016, one-sided; OR = 1.52; 95%-CI: 1.05-2.21). The increase of the delA750
      frequency was accentuated in 312 patients exhibiting typical absence seizures
      (8.8%, P = 0.005, one-sided; OR = 1.72; 95%-CI: 1.13-2.62) relatively to that
      observed in the 237 patients with myoclonic seizures on awakening (7.2%; P =
      0.11, one-sided; OR = 1.36; 95%-CI: 0.85-2.19), when compared with controls. The
      present results suggest that the functional KCNMB3 beta3b-truncation confers a
      common epileptogenic effect preferentially to the ictogenesis of typical absence
      seizures.

PMID- 16958041
TI  - Effect of radioactivity on stent-graft incorporation after endovascular treatment
      of aneurysms: An animal study.
AB  - Poor stent-graft (SG) incorporation into the vessel wall, following endovascular
      repair of abdominal aortic aneurysms (EVAR), can lead to endoleaks and SG
      migration. Low-dose radiation can prevent aneurysm recurrence after coil
      embolization, and has been associated with a "paradoxical" increase in neointima
      formation after stenting in a few studies. It was hypothesized that in situ beta
      radiation emitted from SG could improve its incorporation by preventing the
      persistence of circulating channels between the implant and the vessel wall and
      increasing neointima formation around the SG. Phosphorus 32 ((32)P, 200 or 400
      kBq per SG (n = 6 each)) was ion implanted on the external surface of balloon
      expandable SGs. Twelve radioactive and six non-radioactive SGs were deployed in
      iliac arteries of nine Mongrel dogs. Neointima formation inside the graft and the
      persistence of circulating flow through an artificial groove created during the
      endovascular procedure were assessed by follow-up imaging and by blinded,
      computerized histomorphometric analysis after animal sacrifice at 3 months.
      Occlusion occurred in four radioactive SGs. A lesser number of patent grooves was
      observed along high-activity SGs than along control SGs (1/3 versus 4/4). No
      difference in neointima formation was observed in radioactive and non-radioactive
      SGs. Alteration of external graft surface was observed after ion implantation.
      Ion implantation of (32)P on SGs does not seem to be a viable strategy to improve
      incorporation and prevent type-I endoleak after EVAR.

PMID- 16958042
TI  - Effect of poly(lactic-co-glycolic acid) contact on maturation of murine bone
      marrow-derived dendritic cells.
AB  - Understanding of biomaterial adjuvant effect and its mechanisms is essential for
      the effective design and selection of appropriate materials for specific
      applications. We have previously shown that poly(lactic-co-glycolic acid) (PLGA),
      one of the most commonly studied polymers in tissue engineering, supports an
      adjuvant effect as measured by enhanced immune response against a co-delivered
      model antigen, which was dependent on the form of the biomaterial. Furthermore,
      we have shown that PLGA induces the maturation of human peripheral blood
      mononuclear cell-derived dendritic cells (DCs) in vitro. In this study, the
      effect of PLGA contact on the maturation of murine bone marrow-derived DCs was
      investigated in part to explain the biomaterial adjuvant effect observed.
      Treatment of bone marrow-derived DCs from C57BL6 mice with PLGA microparticles or
      films lead to maturation of these cells as exemplified by increased expression of
      co-stimulatory molecules CD80 and CD86 and production of proinflammatory
      cytokines TNF-alpha and IL-6. These results suggest that PLGA contact induces
      maturation of murine DCs, supporting our observations with human DCs. With the
      techniques developed in this study and given the results, our future goal is to
      utilize transgenic murine models to delineate the mechanisms of biomaterial
      induced DC maturation.

PMID- 16958043
TI  - Rationally designed peptides for controlled release of nerve growth factor from
      fibrin matrices.
AB  - The purpose of this research was to identify peptide sequences with varying
      affinity for nerve growth factor (NGF) and use them in the rational design of
      affinity-based drug delivery systems. A phage display library (12 amino acid
      random peptide sequence) was screened against NGF-conjugated chromatography resin
      three times and fractions containing phage of varying affinity were eluted by
      decreasing the pH of the eluent. These phages were isolated, amplified; then
      their DNA was purified and sequenced to determine the identity of the random
      peptide domain. Consensus peptides based on these sequences were synthesized and
      screened for their ability to bind NGF and release it at different rates from
      fibrin matrices. The ability of fibrin matrices containing these peptides and NGF
      to deliver to biologically active NGF was tested using a chick dorsal root
      ganglia model. A mathematical model was developed to further understand how the
      affinity of a peptide can modulate release of NGF and to aid in design
      optimization for the delivery system. The peptides identified in this study were
      determined to have varying affinities for NGF suggesting that this approach can
      serve as a model for tailoring the affinity of a drug delivery system for a
      target protein drug.

PMID- 16958044
TI  - Complexity in modeling of residual stresses and strains during polymerization of
      bone cement: effects of conversion, constraint, heat transfer, and viscoelastic
      property changes.
AB  - Aseptic loosening of cemented joint prostheses remains a significant concern in
      orthopedic biomaterials. One possible contributor to cement loosening is the
      development of porosity, residual stresses, and local fracture of the cement that
      may arise from the in-situ polymerization of the cement. In-situ polymerization
      of acrylic bone cement is a complex set of interacting processes that involve
      polymerization reactions, heat generation and transfer, full or partial
      mechanical constraint, evolution of conversion- and temperature-dependent
      viscoelastic material properties, and thermal and conversion-driven changes in
      the density of the cement. Interactions between heat transfer and polymerization
      can lead to polymerization fronts moving through the material. Density changes
      during polymerization can, in the presence of mechanical constraint, lead to the
      development of locally high residual strain energy and residual stresses. This
      study models the interactions during bone cement polymerization and determines
      how residual stresses develop in cement and incorporates temperature and
      conversion-dependent viscoelastic behavior. The results show that the presence of
      polymerization fronts in bone cement result in locally high residual strain
      energies. A novel heredity integral approach is presented to track residual
      stresses incorporating conversion and temperature dependent material property
      changes. Finally, the relative contribution of thermal- and conversion-dependent
      strains to residual stresses is evaluated and it is found that the conversion
      based strains are the major contributor to the overall behavior. This framework
      provides the basis for understanding the complex development of residual stresses
      and can be used as the basis for developing more complex models of cement
      behavior.

PMID- 16958045
TI  - Electrophoretic deposition of hydroxyapatite coating on Fecralloy and analysis of
      human osteoblastic cellular response.
AB  - Hydroxyapatite has been successfully deposited onto Fecralloy substrate (a metal
      alloy with 22% Cr, 4.8% Al) by electrophoretic deposition in an attempt to
      promote the adhesion between coating and substrate, consequently to extend the
      lifetime of implants. Fecralloy has the ability to generate a dense and stable
      alpha-Al(2)O(3) layer "in situ" during thermal treatment, which will highly
      improve the adhesion and the corrosion resistance of the coating system. Phases
      and morphologies of HA coating were found to vary after sintering according to
      XRD and SEM analysis. Besides the physicochemical characterization, the effects
      of the Fecralloy, thermally generated oxide layer, and HA coating on the early
      and late responses of osteoblasts in vitro were determined. Cellular morphology
      and proliferation were studied up to 7 days. Quantitative assays of
      mineralization were conducted up to 14 days. Osteoblasts showed increased cell
      spreading and cell proliferation on metal substrates, with significantly higher
      mineralization on HA coating. The results in this study proved that Fecralloy is
      a biocompatible metal and the HA coating on Fecralloy provides a good candidate
      for orthopaedic and dental implants.

PMID- 16958046
TI  - In vivo biostability of polyether polyurethanes with fluoropolymer and
      polyethylene oxide surface modifying endgroups; resistance to metal ion
      oxidation.
AB  - Polyether polyurethanes are subject to oxidation catalyzed by, and through direct
      (redox) reaction with transition metal ions (metal ion oxidation, MIO). The
      source of the ions is corrosion of metallic parts within an implanted device. A
      Shore 80A polyether polyurethane was modified with fluoropolymer (E80AF) or
      polyethylene oxide (E80AP) surface modifying end groups (SME). The SME migrates
      to the surface to form a covalently bonded monolayer, while maintaining the bulk
      properties of the polyurethane. In vitro tests in H(2)O(2) solution indicated
      that both SME's accelerated MIO. Tubing samples containing cobalt mandrels were
      implanted in the subcutis of rabbits for up to 2 years. In vivo, E80AF
      significantly slowed the rate of visible degradation, but did not prevent MIO.
      E80AP had virtually identical visual performance to the unmodified control in
      vivo. Infrared spectroscopy and molecular weight correlated well with visual
      appearance. When cracks were seen, polyether soft segment oxidation was
      occurring. Both E80AP and the control developed severe loss of molecular weight
      in vivo. The changes were much less severe for E80AF. Thus, contrary to in vitro
      test results, the PEO SME had no effect at all on MIO resistance, while the
      fluoropolymer SME produced a significant improvement in biostability.

PMID- 16958047
TI  - Biocompatibility and drug release behavior of spontaneously formed phospholipid
      polymer hydrogels.
AB  - Hydrogels containing 2-methacryloyloxyethyl phosphorylcholine (MPC) moieties were
      formed from aqueous solutions with water-soluble MPC polymers with carboxylic
      acid and alkyl groups because of hydrogen bonding formation. To investigate the
      biocompatibility and drug release behavior of the hydrogels, we used random- and
      block-type carboxylic acid MPC polymers, such as poly [MPC-co-methacrylic acid
      (MA)] (rPMA), poly[MPC-co-4-(2-methacryloyloxyethyl) trimellitic acid (MET)]
      (rPMT), poly (MA-block-MPC-block-MA) (bPMA) and poly(MET-block-MPC-block-MET)
      (bPMT), and alkyl MPC polymers, such as poly[MPC-co-n-butyl methacrylate] (PMB)
      and poly(MPC-co-benzyl methacrylate) (PMBz). We investigated the biocompatibility
      of the spontaneously formed MPC polymer hydrogels by a hemolysis test and an in
      vivo injection test. The random MPC polymers having carboxylic acid groups
      expressed more hemolytic activity compared to the block polymers. The results of
      the in vivo injection test also indicated low biocompatibility of the carboxylic
      acid polymers especially at high concentration. The alkyl MPC polymers, the PMB
      and PMBz showed excellent biocompatibility in both hemolysis and in vivo
      injection test. However, the hydrogels, the rPMA/PMB hydrogel (rABgel) and the
      rPMT/PMBz hydrogel (rTZgel) lowered the hemolytic activity of elemental polymers,
      the rPMA and rPMT. Thus, suppression of the ionization of the carboxylic acid
      groups is necessary for biocompatibility. We also investigated the drug release
      behavior with attention to the interaction between the polymer and the drugs. The
      release behavior of a relatively low-molecular-weight hydrophilic drug, 5
      fluorouracil, did not depend on the structure of the polymers. The higher
      molecular-weight drugs, ketoprofen and indomethacin, were released faster from
      the block polymer hydrogel than the random polymer hydrogel, the rABgel, while
      the highest-molecular-weight drug, doxorubicin, was released faster from the
      random polymer hydrogel. A probable reason for this is the difference in the
      molecular structure; that is, the separated hydrophilic and hydrophobic sections
      in the block polymers constructed pathways where a drug can diffuse. In addition,
      the rTZgel suppressed the release of a drug with a large number of aromatic rings
      probably because of the stacking effect. The results of the compression test also
      suggested the existence of the stacking effect between the rTZgel and the drugs.
      Based on these results, control of drug release is possible by selecting a
      reservoir with an appropriate chemical structure to interact with the drug. For
      example, release of a relatively linear-structured drug with less aromatic rings
      can be suppressed in the rABgel rather than in the rTZgel. Thus, it can be
      concluded that if the ionization is suppressed, these MPC polymer hydrogels can
      be used as a material for a drug reservoir that can be selected according to the
      drug.

PMID- 16958048
TI  - Engineering cartilage with human nasal chondrocytes and a silanized hydroxypropyl
      methylcellulose hydrogel.
AB  - Tissue engineering strategies, based on developing three-dimensional scaffolds
      capable of transferring autologous chondrogenic cells, holds promise for the
      restoration of damaged cartilage. In this study, the authors aimed at determining
      whether a recently developed silanized hydroxypropyl methylcellulose (Si-HPMC)
      hydrogel can be a suitable scaffold for human nasal chondrocytes (HNC)-based
      cartilage engineering. Methyltetrazolium salt assay and cell counting experiments
      first revealed that Si-HPMC enabled the proliferation of HNC. Cell tracker green
      staining further demonstrated that HNC were able to form nodular structures in
      this three-dimensional scaffold. HNC phenotype was then assessed by RT-PCR
      analysis of type II collagen and aggrecan expression as well as alcian blue
      staining of extracellular matrix. Our data indicated that Si-HPMC allowed the
      maintenance and the recovery of a chondrocytic phenotype. The ability of
      constructs HNC/Si-HPMC to form a cartilaginous tissue in vivo was finally
      investigated after 3 weeks of implantation in subcutaneous pockets of nude mice.
      Histological examination of the engineered constructs revealed the formation of a
      cartilage-like tissue with an extracellular matrix containing glycosaminoglycans
      and type II collagen. The whole of these results demonstrate that Si-HPMC
      hydrogel associated to HNC is a convenient approach for cartilage tissue
      engineering.

PMID- 16958049
TI  - RGTA OTR4120, a heparan sulfate mimetic, is a possible long-term active agent to
      heal burned skin.
AB  - Burn-related skin fibrosis leads to loss of tissue function and hypertrophic scar
      formation with damaging consequences for the patient. There is therefore a great
      need for an efficient agent to treat burned skin. We report that ReGeneraTing
      Agent (RGTA) reduces burn-induced skin alteration. The tissue-regenerating effect
      of RGTA OTR4120 was evaluated after 1-6 days and after 10 months in a rat skin
      burn model. This effect was also examined in vitro using fibroblasts isolated
      from control and 6-day-old burned skins. We measured production of dermal
      collagen I, III, and V and activities of metalloproteinases 2 and 9 (MMP-2 and
      MMP-9). Ratio of collagen III over collagen I production increased 6 days after
      the burn, because of a decrease in collagen I production. After 10 months, ratio
      of collagen III over collagen I in burn sites was still increased compared with
      control skin, because of an increase in collagen III production. Both
      abnormalities were corrected by OTR4120. OTR4120 increased pro- and active MMP-2
      and MMP-9, compared with healthy and burned controls and therefore accelerated
      remodeling. Similar data were obtained with cultured fibroblasts from healthy and
      burned skins. OTR4120 enhanced healing in short- and long-term after burns,
      reducing the formation of fibrotic tissue, and then represents a potential agent
      to improve burned skin healing.

PMID- 16958050
TI  - Poly(hexyl-substituted lactides): novel injectable hydrophobic drug delivery
      systems.
AB  - Poly(hexyl-substituted lactides) (PHLA) as new hydrophobic polyesters with
      controlled molecular weights and narrow distributions were synthesized by ring
      opening polymerization (ROP) using tin(II) 2-ethylhexanoate (Sn(Oct)(2)) and
      benzyl alcohol as catalyst and initiator. Glass transition temperatures (T(g))
      and zero shear viscosities (eta(0)) at 25 degrees C could be modulated from T(g)=
      -42 degrees C to -10 degrees C and 40 to 4850 Pa s, respectively, by varying the
      polymer molecular weight and the number of hexyl groups along the polymer chain.
      Degradation studies were performed in terms of both mass and molecular weight
      loss in the course of time. The degradation mechanism is shown to be of the "bulk
      erosion" type, and comparable to standard poly(D,L-lactide) (PLA). Despite the
      increased steric hindrance in the poly(monohexyl-substituted lactide) (PmHLA) due
      to the hexyl side groups, its degradation rate at pH 7.4 and 37 degrees C was
      found to be slightly higher than observed for the analogue standard PLA. This
      could be attributed to the flexible rubbery state of the hexyl-substituted
      polymer (T(g) approximately -15 degrees C) at the physiological temperature,
      which is favoring the degradation in comparison to the rigid and glassy standard
      PLA (T(g) approximately 40 degrees C). In contrast, degradation studies performed
      at 60 degrees C, where both polymers are above their glass transition
      temperature, confirmed that the degradation rate is lower for the sterically more
      hindered PmHLA. The degradation products were analyzed by ESI-MS. Hydrolysis lead
      first to the corresponding oligo-ester fragments and finally to the nontoxic 2
      hydroxyoctanoic acid and lactic acid. Tetracycline was tested as a model drug for
      release studies. This drug was found to be released faster and in higher amounts
      in its active form from the PHLA matrix than from standard PLA. The results
      presented in this work demonstrate the potential of these hydrophobic polylactide
      based semisolid materials as an alternative to conventional PLA/PLGA for
      injectable drug delivery systems.

PMID- 16958051
TI  - Purified titanium oxide with novel morphologies upon spark anodization of Ti
      alloys in mixed H2SO4/H3PO4 electrolytes.
AB  - The spark anodization behavior of alpha/beta Ti6Al4V and Ti6Al7Nb alloys and of
      alpha c.p. Ti in H2SO4, H3PO4, and mixtures of these acids was studied. Chemical
      depth profiling revealed oxides purified with respect to the substrate alloying
      elements. This was particularly pronounced on Ti alloys spark anodized in
      H2SO4/H3PO4 mixtures, the Al content decreasing continuously towards the surface,
      and V and Nb hardly detectable in the outermost 200 nm. The incorporation of S
      was significantly reduced in mixed electrolytes, while about 8 at-% P was
      present. A novel oxide morphology with "worm-like" features in the micrometer
      range, very different from well-known nano/microporous oxides, was found in mixed
      electrolytes under suitable conditions. Similar but more porous-like morphologies
      were formed on Ti. Simple alpha/beta substrate microstructural considerations
      cannot explain the morphological and chemical observations. Raman spectroscopy
      indicated the presence of mixed anatase, rutile, and brookite phase on anodized
      Ti alloys. Bond strengths of 34 MPa for worm-like and 40-50 MPa for
      nano/microporous morphologies as well as excellent abrasion behavior were found.
      The compatibility of grit-blasting with the spark anodization process for
      creating multitopography surfaces was demonstrated. Neither the observed chemical
      effects, nor the observed particular morphology or the presence of brookite have
      been reported before.

PMID- 16958052
TI  - In vitro pyrogen test--A new test method for solid medical devices.
AB  - Medical devices manufactured for implantation into humans must be free of any
      contamination with viable bacteria. However, remnants of dead bacteria and
      bacterial components alone may induce an inflammatory immune response. Pyrogen
      tests for such inflammatory contaminations are generally performed either by
      determining the content of lipopolysaccharide in rinsing solutions of batch
      samples by limulus amoebocyte lysate assay, by injecting the rinsing solutions
      into rabbits or by implanting batch samples into rabbits and measuring change of
      body temperature. In this study, we show that the in vitro pyrogen test (IPT),
      which measures the release of the inflammatory cytokine IL-1beta in fresh or
      cryopreserved human whole blood, can be used to assess the pyrogenic
      contamination of implantable medical devices. This test was used to check
      neurosurgical implants, namely aneurysm clips, as a proof of principle. Owing to
      the direct contact of the test material with the blood cells, this test does not
      require rinsing procedures, which have variable efficacy. The use of human blood
      ensures the detection of all substances that are pyrogenic for humans and
      reflects their relative potency. The safety of the products as delivered could be
      confirmed. The effects of sterilization and depyrogenization procedures on
      intentional pyrogenic contaminations of samples could be followed. This new
      application of the already internationally validated method promises to replace
      further rabbit pyrogen tests. It generates extremely sensitive results with an
      extended range of detectable pyrogenic contaminants.

PMID- 16958053
TI  - Two central core disease (CCD) deletions in the C-terminal region of RYR1 alter
      muscle excitation-contraction (EC) coupling by distinct mechanisms.
AB  - Central core disease (CCD) and malignant hyperthermia (MH) are skeletal muscle
      disorders that are linked to mutations in the gene that encodes the type 1
      ryanodine receptor (RYR1). The RYR1 ion channel plays a central role in
      excitation-contraction (EC) coupling by releasing Ca(2+) from an internal store.
      Pathogenic CCD mutations in RYR1 result in changes in the magnitude of Ca(2+)
      release during EC coupling. CCD has recently been linked to two novel deletions
      (c.12640_12648delCGCCAGTTC [p.Arg4214_Phe4216del] and c.14779_14784delGTCATC
      [p.Val4927_Ile4928del]) in the C-terminal region of RYR1. To determine the
      phenotypic consequences of these mutations and extend our understanding of the
      pathogenic mechanisms that underlie CCD, we determined functional effects on
      Ca(2+) release channel activity of analogous deletions (p.Arg4215_Phe4217del and
      p.Val4926_Ile4927del) engineered into rabbit RYR1 following expression in RYR1
      null (dyspedic) myotubes and HEK293 cells. In addition, we assessed effects of
      the p.Arg4214 Phe4216del mutation on RYR1 function in lymphoblastoid cells
      obtained from CCD patients heterozygous for the mutation. Here we report that
      both deletions significantly reduce Ca(2+) release following RYR1 activation, but
      by different mechanisms. While the p.Arg4214_Phe4216del deletion promotes Ca(2+)
      depletion from intracellular stores by exhibiting a classic "leaky channel"
      behavior, the p.Val4927_Ile4928del deletion reduces Ca(2+) release by disrupting
      Ca(2+) gating and eliminating Ca(2+) permeation through the open channel.

PMID- 16958054
TI  - Population-based estimates of breast cancer risks associated with ATM gene
      variants c.7271T>G and c.1066-6T>G (IVS10-6T>G) from the Breast Cancer Family
      Registry.
AB  - The ATM gene variants segregating in ataxia-telangiectasia families are
      associated with increased breast cancer risk, but the contribution of specific
      variants has been difficult to estimate. Previous small studies suggested two
      functional variants, c.7271T>G and c.1066-6T>G (IVS10-6T>G), are associated with
      increased risk. Using population-based blood samples we found that 7 out of 3,743
      breast cancer cases (0.2%) and 0 out of 1,268 controls were heterozygous for the
      c.7271T>G allele (P=0.1). In cases, this allele was more prevalent in women with
      an affected mother (odds ratio [OR]=5.5, 95% confidence interval [CI]=1.2-25.5;
      P=0.04) and delayed child-bearing (OR=5.1; 95% CI=1.0-25.6; P=0.05). The
      estimated cumulative breast cancer risk to age 70 years (penetrance) was 52% (95%
      CI=28-80%; hazard ratio [HR]=8.6; 95% CI=3.9-18.9; P<0.0001). In contrast, 13 of
      3,757 breast cancer cases (0.3%) and 10 of 1,268 controls (0.8%) were
      heterozygous for the c.1066-6T>G allele (OR=0.4; 95% CI=0.2-1.0; P=0.05), and the
      penetrance was not increased (P=0.5). These findings suggest that although the
      more common c.1066-6T>G variant is not associated with breast cancer, the rare
      ATM c.7271T>G variant is associated with a substantially elevated risk. Since
      c.7271T>G is only one of many rare ATM variants predicted to have deleterious
      consequences on protein function, an effective means of identifying and grouping
      these variants is essential to assess the contribution of ATM variants to
      individual risk and to the incidence of breast cancer in the population.

PMID- 16958055
TI  - Vascular update: morphogenesis, tumors, malformations, and molecular dimensions.
AB  - This vascular review is organized under the following headings: vasculogenesis
      and angiogenesis; vascular endothelial growth factors, their receptors, TIE
      receptors, and angiopoietins; other factors in blood vessel formation; parallel
      patterning in blood vessels and nerves; physiological and pathological
      neovascularization; the role of VEGF receptors in metastasis; anti-angiogenic
      therapy for tumors; association of blood vessels with fat; vascular malformations
      and vascular tumors; infantile hemangiomas; congenital hemangiomas; lymphatic
      malformations; molecular characteristics of some disorders with vascular
      malformations; Kasabach-Merritt phenomenon; Sturge-Weber syndrome, Klippel
      Trenaunay syndrome, and Parkes Weber syndrome; diagnostic and laboratory studies;
      and future perspectives.

PMID- 16958056
TI  - Idiopathic normal pressure hydrocephalus may be a "two hit" disease: benign
      external hydrocephalus in infancy followed by deep white matter ischemia in late
      adulthood.
AB  - PURPOSE: To determine if normal pressure hydrocephalus (NPH) could result from
      decreased resorption of cerebrospinal fluid (CSF) by the arachnoidal villi,
      leading to benign external hydrocephalus [BEH] in infancy, followed by deep white
      matter ischemia (DWMI) in late adulthood (the more hydrophilic environment
      increasing resistance to CSF flow through the extracellular space (ECS) of the
      brain). MATERIALS AND METHODS: CSF outflow via the fourth ventricle and the ECS
      of the brain was mathematically modeled using a parallel electrical circuit
      analog. The apparent diffusion coefficient (ADC) was measured as a surrogate of
      the amount of water in the ECS in normals, patients with symptomatic NPH, and
      patients with dilated ventricles without symptoms of NPH ("pre-NPH"). RESULTS:
      The electrical circuit model demonstrates increasing ventricular volume with
      increasing resistance to flow through the ECS of the brain. ADC measurements
      performed in the centrum semiovale are significantly higher in patients with NPH
      and "pre-NPH" than in age-matched controls (P<0.05), controlling for the same
      degree of DWMI indicating increased fluid in the ECS of the brain. CONCLUSION:
      The electrical circuit analog and finding of increased periventricular ADC
      support the theory that NPH is a "two hit" disease.

PMID- 16958057
TI  - Imaging artifacts at 3.0T.
AB  - Clinical MRI at a field strength of 3.0T is finding increasing use. However,
      along with the advantages of 3.0T, such as increased SNR, there can be drawbacks,
      including increased levels of imaging artifacts. Although every imaging artifact
      observed at 3.0T can also be present at 1.5T, the intensity level is often higher
      at 3.0T and thus the artifact is more objectionable. This review describes some
      of the imaging artifacts that are commonly observed with 3.0T imaging, and their
      root causes. When possible, countermeasures that reduce the artifact level are
      described.

PMID- 16958058
TI  - Brain MRI: tumor evaluation.
AB  - The designation "brain tumors" is commonly applied to a wide variety of
      intracranial mass lesions that are distinct in their location, biology,
      treatment, and prognosis. Since many of these lesions do not arise from brain
      parenchyma, the more appropriate term would be "intracranial tumors." The term
      "tumor" is used to include both neoplastic and non-neoplastic mass lesions, and
      should be considered in its broadest sense to simply indicate a space-occupying
      mass. This review describes an imaging-based approach for evaluating intracranial
      tumors. Conventional MRI is discussed in the setting of a regional classification
      system. This system provides a framework for analysis, and imaging clues can then
      be applied to narrow the differential possibilities. Emphasis is placed on
      advanced MRI techniques and their utility for deciphering common diagnostic
      problems.

PMID- 16958059
TI  - Genetically engineered Bifidobacterium animalis expressing the Salmonella
      flagellin gene for the mucosal immunization in a mouse model.
AB  - BACKGROUND: A critical component of the host defense against enteric infections
      is the immunological response of the mucosal membrane, a major starting point of
      infectious disease, such as typhoid fever. The mucosal immune system consists of
      an integrated network of lymphoid tissues, mucous membrane-associated cells, and
      effector molecules. In the present study, we developed a recombinant
      Bifidobacterium animalis (B. animalis) genetically modified with the Salmonella
      flagellin gene for mucosal immunization as an oral typhoid vaccine. METHODS: We
      constructed an oral vaccine against Salmonella typhimurium, consisting of
      recombinant B. animalis containing the flagellin gene of Salmonella. The
      recombinant B. animalis was administered orally to mice every other day for 6
      weeks. Anti-flagellin antibodies in the serum and stools were measured by enzyme
      linked immunosorbent assay (ELISA). RESULTS: We detected significantly higher
      levels of flagellin-specific IgA in the serum and stools of the mice treated with
      the recombinant B. animalis containing the flagellin gene than was seen in those
      treated with parental B. animalis. CONCLUSIONS: Our findings suggest that an oral
      vaccination using recombinant B. animalis genetically modified with the flagellin
      gene of Salmonella may be effective against Salmonella infections.

PMID- 16958060
TI  - Urokinase-type plasminogen activator gene therapy in liver cirrhosis is mediated
      by collagens gene expression down-regulation and up-regulation of MMPs, HGF and
      VEGF.
AB  - Human urokinase-type plasminogen activator (uPA) gene administration via an
      adenoviral (Ad)-vector induced cirrhosis regression and ameliorated hepatic
      dysfunction in a model of experimental liver cirrhosis. The administration of a
      single dose of 6 x 10(11) viral particles per kilogram of a clinical-grade Ad
      vector was evaluated after the onset of rat liver cirrhosis via degradation of
      deposited collagen and a substantial decrease of alpha-sma-positive cells. Also,
      gene expression for pro-fibrogenic molecules (Col I, III, IV, TIMP-1 and PAI-1)
      was clearly down-regulated. In contrast, gene expression for collagen-degrading
      enzymes such as MMP-13 and MMP-2 was up-regulated. These events correlated with
      increased amounts of proteic free-TIMP-1, i.e. non-complexed with
      metalloproteinases (MMPs), indicating the presence of higher amounts of active
      MMPs inside the liver of cirrhotic animals treated with Ad-huPA. The harmonized
      and concerted expression of HGF and c-met resulted in exacerbated hepatocyte
      proliferation, although these events did not induce an abnormal liver growth.
      Angiogenesis, i.e. formation of new blood vessels, was evaluated by vascular
      endothelial growth factor (VEGF) expression which was notably detected to be 10
      times higher during the first 6 days after Ad-huPA-treatment in cirrhotic animals
      as compared with controls. These events provide a clearer rationale as to how Ad
      huPA-induced liver regeneration on CCl(4)-induced liver fibrosis takes place.

PMID- 16958061
TI  - Evaluation of different cerebral mass lesions by perfusion-weighted MR imaging.
AB  - PURPOSE: To investigate the contribution of perfusion-weighted MR imaging (PWI)
      by using the relative cerebral blood volume (rCBV) ratio in the differential
      diagnosis of various intracranial space-occupying lesions. MATERIALS AND METHODS:
      This study involved 105 patients with lesions (high-grade glioma (N=26), low
      grade glioma (N=11), meningioma (N=23), metastasis (N=25), hemangioblastoma
      (N=6), pyogenic abscess (N=4), schwannoma (N=5), and lymphoma (N=5)). The
      patients were examined with a T2*-weighted (T2*W) gradient-echo single-shot EPI
      sequence. The rCBV ratios of the lesions were obtained by dividing the values
      obtained from the normal white matter. Statistical analysis was performed with
      the Mann-Whitney U-test. A P-value less than 0.05 was considered statistically
      significant. RESULTS: The rCBV ratio was 5.76+/-3.35 in high-grade gliomas,
      1.69+/-0.51 in low-grade gliomas, 8.02+/-3.89 in meningiomas, 5.27+/-3.22 in
      metastases, 11.36+/-4.41 in hemangioblastomas, 0.76+/-0.12 in abscesses, 1.10+/
      0.32 in lymphomas, and 3.23+/-0.81 in schwannomas. The rCBV ratios were used to
      discriminate between 1) high- and low-grade gliomas (P<0.001), 2)
      hemangioblastomas and metastases (P<0.05), 3) abscesses from high-grade gliomas
      and metastases (P<0.001), 4) schwannomas and meningiomas (P<0.001), 5) lymphomas
      from high-grade gliomas and metastases (P<0.001), and 6) typical meningiomas and
      atypical meningiomas (P<0.01). CONCLUSION: rCBV ratios can help discriminate
      intracranial space-occupying lesions by demonstrating lesion vascularity. It is
      possible to discriminate between 1) high- and low-grade gliomas, 2)
      hemangioblastomas and other intracranial posterior fossa masses, 3) abscesses
      from high-grade gliomas and metastases, 4) schwannomas and meningiomas, 5)
      lymphomas and high-grade gliomas and metastases, and 6) typical and atypical
      meningiomas.

PMID- 16958062
TI  - Magnetic resonance angiography of the human middle meningeal artery: implications
      for migraine.
AB  - PURPOSE: To describe a novel noninvasive method for studying middle meningeal
      artery (MMA) diameter changes in vivo in humans. Dilatation of the MMA has been
      implicated in the pathophysiology of migraine headache, but no direct evidence
      has been obtained in humans. MATERIALS AND METHODS: The diameter of the MMA (the
      extracranial part) was measured in 19 healthy volunteers before and after
      administration of a vasodilator (nitroglycerin (NTG), 1.2 mg sublingually) known
      to provoke headache. We used magnetic resonance angiography (MRA) in combination
      with a 47-mm microscopy coil and a semiautomatic contour detection program.
      RESULTS: The diameter of the MMA was 1.5+/-0.26 mm (mean+/-SD) before and 1.79+/
      0.30 mm after NTG administration. This increase was 20.1% (95% CI=12.9-27.3;
      P<0.001). The mean increase in subjects who developed headache (N=11) was 0.34+/
      0.19 mm as compared to 0.22 mm+/-0.20 mm in the eight subjects who did not (95%
      CI for difference=-0.07 to 0.31; P=0.188). CONCLUSION: MRA in combination with a
      47-mm microscopy coil is a novel, noninvasive method to measure changes in the
      diameter of human meningeal vessels, with potential applications for migraine and
      other fields of neurovascular research.

PMID- 16958063
TI  - 1H NMR spectroscopic imaging of the mouse brain at 9.4 T.
AB  - PURPOSE: To assess the feasibility of 1H spectroscopic imaging (SI) in the mouse
      brain at 9.4 T, and investigate regional variations in brain metabolites.
      MATERIALS AND METHODS: A total of 21 SI studies were performed in CD-1 mice to
      evaluate the basal ganglia (N=5), hippocampus and thalamus (N=11), and cerebellum
      (N=5). We adjusted the B0 homogeneity for each slice using a fully automated shim
      calculation method based on the B0 map, which we measured using a multislice
      gradient-echo sequence with multiple phase evolution delays. The SI employed a
      modified localization by adiabatic selective refocusing (LASER) sequence with
      TE/TR of 50/2000 msec, 24x24 encodes over a field of view (FOV) of 24 mmx24 mm, 1
      microL voxel resolution, and two averages, for a total acquisition time of 38
      minutes. RESULTS: Sufficient shimming was achieved and high-quality spectra were
      consistently obtained in each slice. N-acetyl aspartate (NAA)/creatine (Cr)
      ratios in the basal ganglia and thalamus (0.86+/-0.07, and 0.87+/-0.07,
      respectively) were significantly higher than those in the hippocampus and
      cerebellum (0.76+/-0.03 and 0.67+/-0.07), which were also significantly different
      from each other. CONCLUSION: 1H SI of the mouse brain is highly reproducible and
      allows differences in regional metabolite ratios to be easily visualized.

PMID- 16958064
TI  - Simultaneous imaging and R2* mapping using a radial multi-gradient-echo (rMGE)
      sequence.
AB  - PURPOSE: To demonstrate a rapid MR technique that combines imaging and R2*
      mapping based on a single radial multi-gradient-echo (rMGE) data set. The
      technique provides a fast method for online monitoring of the administration of
      (super-)paramagnetic contrast agents as well as image-guided drug delivery.
      MATERIALS AND METHODS: Data are acquired using an rMGE sequence, resulting in
      interleaved undersampled radial k-spaces representing different echo times (TEs).
      These data sets are reconstructed separately, yielding a series of images with
      different TEs used for pixelwise R2* mapping. A fast numerical algorithm
      implemented on a real-time reconstruction platform provides online estimation of
      the relaxation rate R2*. Simultaneously the images are summed for the computation
      of a high-resolution image. RESULTS: Convenient high-resolution R2* maps of
      phantoms and the liver of a healthy volunteer were obtained. In addition to
      stable intrinsic baseline maps, the proposed technique provides particularly
      accurate results for the high relaxation rates observed during the presence of
      (super-)paramagnetic contrast agents. Assuming that the change in R2* is
      proportional to the concentration of the agent, the technique offers a rough
      estimate for dynamic dosage. CONCLUSION: The simultaneous online display of
      morphological and parametric information permits convenient, quantitative
      surveillance of contrast-agent administration.

PMID- 16958065
TI  - SENSE imaging with a quadrature half-volume transverse electromagnetic (TEM) coil
      at 4T.
AB  - PURPOSE: To demonstrate the feasibility of high-field SENSE imaging of large
      objects, such as the human head, using a semicircular (half-volume) coil for both
      transmission and multi-channel reception. MATERIALS AND METHODS: As a proof of
      concept, we present experimental data obtained using a seven-element half-volume
      (180 degrees of arc) transmit/receive quadrature transverse electromagnetic (TEM)
      coil. SENSE images of the human brain were acquired with a reduction factor of
      R=2, using two degenerate linear modes of the same coil as independent receive
      channels at 4T. Since the need for additional hardware (i.e., a separate set of
      receive coils) is eliminated, the design can be substantially simplified.
      RESULTS: The experimental data demonstrate that linear modes of the half-volume
      TEM coil have essentially no noise correlation, and their sensitivity profiles
      satisfy the requirement for small g-factors. Also, this type of coil provides
      efficient transmission with a relatively large uniform region and a reception
      profile that is more uniform than that of the surface coils. CONCLUSION: We
      demonstrate the feasibility of SENSE imaging using a half-volume coil. Half
      volume coils allow reduced total power deposition compared to full-volume coils,
      and may replace the latter in body imaging applications in which the target
      region of interest (ROI) is smaller than the entire torso.

PMID- 16958066
TI  - Towards a better understanding of the unusual conformations of the alternating
      guanine-adenine repeat strands of DNA.
AB  - Alternating guanine-adenine strands of DNA are known to self-associate into a
      parallel-stranded homoduplex at neutral pH, fold into an ordered single-stranded
      structure at acid pH, and adopt yet another ordered single-stranded conformer in
      aqueous ethanol. The unusual conformers melt cooperatively and exhibit distinct
      circular dichroism spectra suggestive of a substantial conformational order, but
      their molecular structures are not known yet. Here, we have probed the molecular
      structures using guanine and adenine analogs lacking the N7 atom, and thus unable
      of Hoogsteen pairing, or those restrained in the less-frequent syn glycosidic
      orientation. The studies showed that the syn glycosidic orientation of dA
      residues promoted the neutral homoduplex, whereas the syn orientation of dG was
      incompatible with the homoduplex. In addition, Hoogsteen pairing of dA seemed to
      be a crucial property of the homoduplex whereas dG did not pair in this way. The
      situation was the same in both single-stranded conformers with the dG residues.
      On the other hand, the presence of N7 was important with dA but its syn geometry
      was not favorable. The present data can be used as restraints to model the
      unusual molecular structures of the alternating guanine-adenine strands of DNA.

PMID- 16958067
TI  - Dynamic MR venography: an intrinsic benefit of time-resolved MR angiography.
AB  - PURPOSE: To investigate the possibility of obtaining dynamic contrast-enhanced
      magnetic resonance venography (DCE-MRV) images of the lower extremities.
      MATERIALS AND METHODS: Peripheral contrast-enhanced magnetic resonance
      angiography (CE-MRA) was performed on 20 patients using a time-resolved sequence
      that combined undersampled projection reconstruction (PR) in-plane and Cartesian
      slice encoding through-plane. The contrast dynamics of distal vessels were
      depicted. An automated segmentation algorithm based on a contrast arrival time
      (CAT) threshold was used to generate contrast dynamics in the venous system. The
      signal difference between the vein and artery was measured to evaluate the
      effectiveness of this technique in isolating the venous contrast dynamics.
      RESULTS: The automatically generated image series depicted the contrast dynamics
      of both the arterial and venous systems, including asymmetric venous enhancement
      and background tissue enhancement. Quantitative measurement showed a mean
      venous/arterial signal ratio increase from 1.58 to 4.82 for the peak venous frame
      after arterial signal suppression. CONCLUSION: DCE-MRV is a minimally invasive
      technique for evaluating the venous side of the systemic vascular anatomy. Time
      resolved MRA has the potential clinical benefit of enabling both arterial and
      venous disease to be detected in patients undergoing CE-MRA.

PMID- 16958068
TI  - Dynamics of lateral ventricle and cerebrospinal fluid in normal and hydrocephalic
      brains.
AB  - PURPOSE: To develop quantitative MRI techniques to measure, model, and visualize
      cerebrospinal fluid (CSF) hydrodynamics in normal subjects and hydrocephalic
      patients. MATERIALS AND METHODS: Velocity information was obtained using time
      resolved (CINE) phase-contrast imaging of different brain regions. A technique
      was developed to measure the change of lateral ventricle (LV) size. The temporal
      relationships between the LV size change, CSF movement, and blood flow could then
      be established. The data were incorporated into a first-principle CSF
      hydrodynamic model. The model was then used to generate specific predictions
      about CSF pressure relationships. To better-visualize the CSF flow, a color
      coding technique based on linear transformations was developed that represents
      the magnitude and direction of the velocity in a single cinematic view. RESULTS:
      The LV volume change of the eight normal subjects was 0.901+/-0.406%.
      Counterintuitively, the LV decreases as the choroid plexus expands, so that they
      act together to produce the CSF oscillatory flow. The amount of oscillatory flow
      volume is 21.7+/-10.6% of the volume change of the LV from its maximum to its
      minimum. CONCLUSION: The quantification and visualization techniques, together
      with the mathematical model, provide a unique approach to understanding CSF flow
      dynamics.

PMID- 16958069
TI  - Contrast enhancement of manganese-hydroxypropyl-tetraacetic acid, an MR contrast
      agent with potential for detecting differences in myocardial blood flow.
AB  - PURPOSE: To determine whether the contrast agent MnHPTA has potential for
      detecting differences in myocardial blood flow. MATERIALS AND METHODS: R1 in the
      myocardium was calculated from MR signal intensity measurements in 18 pigs after
      intravenous injection of 5, 15, or 25 micromol MnHPTA/kg body weight.
      Measurements were made in each animal after administration at rest and during
      dobutamine-induced stress. RESULTS: A difference of approximately 0.1 sec-1 in
      the R1 increase between rest and stress still remained 31 minutes after
      administration of 25 micromol MnHPTA/kg body weight. When two consecutive MnHPTA
      injections were performed, the second injection induced a lower R1 increase than
      the corresponding first injection. CONCLUSION: MnHPTA at a dose of 25 micromol/kg
      body weight (b.w.) has the potential to detect perfusion differences in
      myocardium. When two consecutive injections of MnHPTA were administered, the R1
      change after the second injection was affected by the earlier administration.
      Therefore, a protocol including more than one administration is not ideal for
      this contrast agent.

PMID- 16958070
TI  - Exploring the limits of RF shimming for high-field MRI of the human head.
AB  - Several methods have been proposed for overcoming the effects of radiofrequency
      (RF) magnetic field inhomogeneity in high-field MRI. Some of these methods rely
      at least in part on the ability to independently control magnitude and phase of
      different drives in either one multielement RF coil or in different RF coils in a
      transmit array. The adjustment of these drive magnitudes and phases alone to
      create uniform RF magnetic (B(1)) fields has been called RF shimming, and has
      certain limits at every frequency as dictated by possible solutions to Maxwell's
      equations. Here we use numerical calculations to explore the limits of RF
      shimming in the human head. We found that a 16-element array can effectively shim
      a single slice at frequencies up to 600 MHz and the whole brain at up to 300 MHz,
      while an 80-element array can shim the whole brain at up to 600 MHz.

PMID- 16958071
TI  - Quantification of the expression level of integrin receptor alpha(v)beta3 in cell
      lines and MR imaging with antibody-coated iron oxide particles.
AB  - Targeted imaging requires site-specific accumulation of a contrast agent (CA),
      and the properties of that agent must be selected according to the abundance of
      the target to obtain a signal above the detection limit of the instrument.
      However, numerical estimates of receptors per cell are rarely found in the
      literature. Integrin receptors would be particularly promising targets because of
      their accessibility from the blood stream and expression on activated neovascular
      endothelial cells. We systematically estimated the number of integrin receptors
      of cell lines and primary cells by flow cytometry analysis. Since integrin
      receptors are heterodimeric molecules, and alpha(v) forms complexes with various
      beta subunits, the numbers of alpha(v) and beta(3) subunits are therefore
      dissimilar. The observed values are 3 . 10(3)-1.4 . 10(4)/cell for alpha(v), and
      5.3 . 10(2)-1.1 . 10(4)/cell for beta(3). Despite the low number of exposed
      receptors, we show that up to single-cell MR visualization can be achieved with
      the use of iron oxide beads complexed with antibodies as CAs.

PMID- 16958073
TI  - Just how much data need to be collected for reliable bootstrap DT-MRI?
AB  - Diffusion tensor MRI (DT-MRI) can provide estimates of fiber orientation derived
      from the orientational dependence of the diffusivity of water molecules, enabling
      the reconstruction of white matter fiber pathways using tractography methods.
      However, noise arising from various sources can introduce uncertainty into the
      estimates of the elements of the diffusion tensor, resulting in errors in fiber
      orientation estimates such that tractography reconstructions of fiber pathways
      potentially can be imprecise and inaccurate. Recently, attempts have been made to
      characterize the uncertainty in DT-MRI-derived parameters using the bootstrap
      method; however, several questions remain open regarding the number of repeat
      measurements and bootstraps required to accurately and precisely reconstruct the
      probability distributions of the DT-MRI parameters. This study investigates the
      accuracy and precision of the bootstrap method for characterizing distributions
      of DT-MRI parameters. A number of experimental bootstrap designs and sampling
      schemes containing different numbers of isotropically distributed gradient
      vectors are considered, using an idealized system where the true variability in
      each parameter is known. This study demonstrates that for most DT-MRI
      experiments, robust results will be obtained if the minimum number of bootstraps
      is approximately 500, and that at least five repeat samples of each diffusion
      weighted intensity should be used for bootstrapping.

PMID- 16958074
TI  - Quantification of intravoxel velocity standard deviation and turbulence intensity
      by generalizing phase-contrast MRI.
AB  - Turbulent flow, characterized by velocity fluctuations, is a contributing factor
      to the pathogenesis of several cardiovascular diseases. A clinical noninvasive
      tool for assessing turbulence is lacking, however. It is well known that the
      occurrence of multiple spin velocities within a voxel during the influence of a
      magnetic gradient moment causes signal loss in phase-contrast magnetic resonance
      imaging (PC-MRI). In this paper a mathematical derivation of an expression for
      computing the standard deviation (SD) of the blood flow velocity distribution
      within a voxel is presented. The SD is obtained from the magnitude of PC-MRI
      signals acquired with different first gradient moments. By exploiting the
      relation between the SD and turbulence intensity (TI), this method allows for
      quantitative studies of turbulence. For validation, the TI in an in vitro flow
      phantom was quantified, and the results compared favorably with previously
      published laser Doppler anemometry (LDA) results. This method has the potential
      to become an important tool for the noninvasive assessment of turbulence in the
      arterial tree.

PMID- 16958075
TI  - Fusion patterns of craniofacial sutures in rhesus monkey skulls of known age and
      sex from Cayo Santiago.
AB  - Bones of the face and cranial vault meet at sutural boundaries. These sutures are
      of great importance for craniofacial growth. Although the effects that the
      sutures have on modulating craniofacial strains have been investigated, how
      sutural fusion influences primate craniofacial biomechanics and adaptation are
      less considered. Confounding this problem is the lack of any systematic data on
      patterns of craniofacial sutural fusion from animals of known age and sex. This
      study examined the status of 28 sutures in Macaca mulatta skulls from a
      collection of animals of known age and sex from Cayo Santiago, Puerto Rico.
      Survival analysis showed that most animals died before all sutures fused. There
      was high variation in the age at which individual sutures or sutural sections
      were fused in M. mulatta, and significant differences in the amount of sutural
      fusion among regions and between males and females. Intensive fusion of sutures
      took place between ages 5 and 15. Sutures in the facial area tended to be less
      fused than in the cranial vault. Between adolescence and adulthood, males tended
      to have more sutural fusion than females, especially in the facial area. These
      differences might be biomechanical adaptations during ontogeny to craniofacial
      sexual dimorphism. These findings enrich our understanding of variation in
      sutural morphology in rhesus monkeys. Comparative information across primate
      species is essential for understanding the biomechanics of craniofacial form
      throughout primate evolution.

PMID- 16958076
TI  - Diffusional kurtosis imaging in the lung using hyperpolarized 3He.
AB  - Diseases of the small airspaces represent an increasingly important health
      problem. Asthma is primarily a disease of airway dysfunction, while chronic
      obstructive pulmonary disease (COPD) is associated with abnormalities in both the
      small airways and the alveoli. Conventional diffusion magnetic resonance imaging
      (MRI) of hyperpolarized noble gases, because of the short T(2)* of the gas, is
      only capable of monitoring diffusion over short times and hence only short
      distances. Diffusion imaging is therefore only sensitive to changes in small
      structures of the lung (primarily the alveoli), and will not adequately
      interrogate diffusion along the longitudinal axes of bronchi and bronchioles. In
      this communication we present a new method, termed diffusional kurtosis imaging
      (DKI), that is particularly sensitive to diffusion over longer distances. DKI may
      therefore be more sensitive to abnormalities in the bronchioles and bronchi than
      conventional diffusion imaging. Preliminary DKI measurements on healthy human
      subjects and one patient with symptoms suggestive of small airway disease are
      presented. Although the apparent diffusion coefficient (ADC) in the patient was
      similar to that in the normal controls, diffusional kurtosis was markedly
      reduced. This suggests that DKI measurements may be useful for assessing diseases
      of the small airways.

PMID- 16958077
TI  - Do food availability, parasitism, and stress have synergistic effects on red
      colobus populations living in forest fragments?
AB  - Identifying factors that influence animal density is a fundamental goal in
      ecology that has taken on new importance with the need to develop informed
      management plans. This is particularly the case for primates as the tropical
      forest that supports many species is being rapidly converted. We use a system of
      forest fragments adjacent to Kibale National Park, Uganda, to examine if food
      availability and parasite infections have synergistic affects on red colobus
      (Piliocolobus tephrosceles) abundance. Given that the size of primate populations
      can often respond slowly to environmental changes, we also examined how these
      factors influenced cortisol levels. To meet these objectives, we monitored
      gastrointestinal parasites, evaluated fecal cortisol levels, and determined
      changes in food availability by conducting complete tree inventories in eight
      fragments in 2000 and 2003. Red colobus populations declined by an average of 21%
      among the fragments; however, population change ranged from a 25% increase to a
      57% decline. The cumulative basal area of food trees declined by an average of
      29.5%; however, forest change was highly variable (a 2% gain to a 71% decline).
      We found that nematode prevalence averaged 58% among fragments (range 29-83%).
      The change in colobus population size was correlated both with food availability
      and a number of indices of parasite infections. A path analysis suggests that
      change in food availability has a strong direct effect on population size, but it
      also has an indirect effect via parasite infections.

PMID- 16958078
TI  - Life history in male mandrills (Mandrillus sphinx): physical development,
      dominance rank, and group association.
AB  - We assess life history from birth to death in male mandrills (Mandrillus sphinx)
      living in a semifree-ranging colony in Gabon, using data collected for 82 males
      that attained at least the age of puberty, including 33 that reached adulthood
      and 25 that died, yielding data for their entire lifespan. We describe patterns
      of mortality and injuries, dominance rank, group association, growth and stature,
      and secondary sexual character expression across the male lifespan. We examine
      relationships among these variables and investigate potential influences on male
      life history, including differences in the social environment (maternal rank and
      group demography) and early development, with the aim of identifying
      characteristics of successful males. Sons of higher-ranking females were more
      likely to survive to adulthood than sons of low-ranking females. Adolescent males
      varied consistently in the rate at which they developed, and this variation was
      related to a male's own dominance rank. Males with fewer peers and sons of higher
      ranking and heavier mothers also matured faster. However, maternal variables were
      not significantly related to dominance rank during adolescence, the age at which
      males attained adult dominance rank, or whether a male became alpha male. Among
      adult males, behavior and morphological development were related to a male's own
      dominance rank, and sons of high-ranking females were larger than sons of low
      ranking females. Alpha males were always the most social, and the most brightly
      colored males, but were not necessarily the largest males present. Finally, alpha
      male tenure was related to group demography, with larger numbers of rival adult
      males and maturing adolescent males reducing the time a male spent as alpha male.
      Tenure did not appear to be related to characteristics of the alpha male himself.

PMID- 16958079
TI  - Health expenditure growth: reassessing the threat of ageing.
AB  - In this paper we evaluate the respective effects of demographic change, changes
      in morbidity and changes in practices on growth in health care expenditures. We
      use microdata, i.e. representative samples of 3441 and 5003 French individuals
      observed in 1992 and 2000. Our data provide detailed information about morbidity
      and allow us to observe three components of expenditures: ambulatory care,
      pharmaceutical and hospital expenditures. We propose an original microsimulation
      method to identify the components of the drift observed between 1992 and 2000 in
      the health expenditure age profile. On the one hand, we find empirical evidence
      of health improvement at a given age: changes in morbidity induce a downward
      drift of the profile. On the other hand, the drift due to changes in practices is
      upward and sizeable. Detailed analysis attributes most of this drift to
      technological innovation. After applying our results at the macroeconomic level,
      we find that the rise in health care expenditures due to ageing is relatively
      small. The impact of changes in practices is 3.8 times larger. Furthermore,
      changes in morbidity induce savings which more than offset the increase in
      spending due to population ageing.

PMID- 16958080
TI  - A sequential model of older workers' labor force transitions after a health
      shock.
AB  - In this paper we estimate and validate a three-period sequential model of older
      workers' labor force transitions following a health/disability shock, using
      retrospective information from Spanish cross-section data. Central to the
      analysis are the effects of the various disabilities and their severity. We find
      that the probability of remaining employed decreases both with age and the
      severity of the shock. Moreover, we find strong interactions between age and
      severity for older workers and none for prime-age workers. Suffering any kind of
      disability reduces the probability of being employed immediately prior to
      retirement age, and in such cases it is severity which is the strongest
      indicator. With respect to demographics, we find that female gender, having a
      retired spouse or being married all reduce the probabilities of both remaining in
      employment and returning to work following a spell of inactivity; in turn,
      principal breadwinner status, education and skill levels increase this
      likelihood.

PMID- 16958081
TI  - Treatment intensity and provider remuneration: dentists in the British National
      Health Service.
AB  - Dental service providers in the British National Health Service (NHS) operate
      under a number of remuneration arrangements that give rise to different
      incentives. Using data derived from the Scottish dental system, we examine the
      relationships between remuneration, patient exemption status and treatment
      intensity. After controlling for differences in patient need and dentist-specific
      preferences, we find that self-employed dentists treat patients who are exempt
      from payment more intensively than their salaried counterparts. The results imply
      that changes in remuneration can have a large effect on the distribution of
      treatments. More generally, our results provide support for economic models that
      view financial incentives as important determinants of physician behaviour.

PMID- 16958083
TI  - Annual report to the nation on the status of cancer, 1975-2003, featuring cancer
      among U.S. Hispanic/Latino populations.
AB  - BACKGROUND: The American Cancer Society, Centers for Disease Control and
      Prevention, National Cancer Institute, and North American Association of Central
      Cancer Registries collaborate annually to provide U.S. cancer information, this
      year featuring the first comprehensive compilation of cancer information for U.S.
      Latinos. METHODS: Cancer incidence was obtained from 90% of the Hispanic/Latino
      and 82% of the U.S. populations. Cancer deaths were obtained for the entire U.S.
      population. Cancer screening, risk factor, incidence, and mortality data were
      compiled for Latino and non-Latino adults and children (incidence only). Long
      term (1975-2003) and fixed-interval (1995-2003) trends and comparative analyses
      by disease stage, urbanicity, and area poverty were evaluated. RESULTS: The long
      term trend in overall cancer death rates, declining since the early 1990s,
      continued through 2003 for all races and both sexes combined. However, female
      lung cancer incidence rates increased from 1975 to 2003, decelerating since 1991
      and breast cancer incidence rates stabilized from 2001 to 2003. Latinos had lower
      incidence rates in 1999-2003 for most cancers, but higher rates for stomach,
      liver, cervix, and myeloma (females) than did non-Latino white populations.
      Latino children have higher incidence of leukemia, retinoblastoma, osteosarcoma,
      and germ-cell tumors than do non-Latino white children. For several common
      cancers, Latinos were less likely than non-Latinos to be diagnosed at localized
      stages. CONCLUSIONS: The lower cancer rates observed in Latino immigrants could
      be sustained by maintenance of healthy behaviors. Some infection-related cancers
      in Latinos could be controlled by evidence-based interventions. Affordable,
      culturally sensitive, linguistically appropriate, and timely access to cancer
      information, prevention, screening, and treatment are important in Latino
      outreach and community networks.

PMID- 16958084
TI  - Income-related reporting heterogeneity in self-assessed health: evidence from
      France.
AB  - This paper tests for income-related reporting heterogeneity in self-assessed
      health (SAH). It also constructs a synthetic measure of clinical health to
      decompose the effect of income on SAH into an effect on clinical health (which is
      called a health production effect) and a reporting heterogeneity effect. We find
      health production effects essentially for low-income individuals, and reporting
      heterogeneity for the choice between the medium labels, i.e. 'fair' vs 'good' and
      for high-income individuals. As such, SAH should be used cautiously for the
      assessment of income-related health inequalities in France. It is however
      possible to minimize the reporting heterogeneity bias by converting SAH into a
      binary variable for poor health vs other health statuses.

PMID- 16958085
TI  - Afferent and efferent connections of the rat retrotrapezoid nucleus.
AB  - The rat retrotrapezoid nucleus (RTN) contains candidate central chemoreceptors
      that have extensive dendrites within the marginal layer (ML). This study
      describes the axonal projections of RTN neurons and their probable synaptic
      inputs. The ML showed a dense plexus of nerve terminals immunoreactive (ir) for
      markers of glutamatergic (vesicular glutamate transporters VGLUT1-3), gamma
      aminobutyric acid (GABA)-ergic, adrenergic, serotonergic, cholinergic, and
      peptidergic transmission. The density of VGLUT3-ir terminals tracked the location
      of RTN chemoreceptors. The efferent and afferent projections of RTN were studied
      by placing small iontophoretic injections of anterograde (biotinylated dextran
      amine; BDA) and retrograde (cholera toxin B) tracers where RTN chemoreceptors
      have been previously recorded. BDA did not label the nearby C1 cells. BDA-ir
      varicosities were found in the solitary tract nucleus (NTS), all ventral
      respiratory column (VRC) subdivisions, A5 noradrenergic area, parabrachial
      complex, and spinal cord. In each target region, a large percentage of the BDA-ir
      varicosities was VGLUT2-ir (41-83%). Putative afferent input to RTN originated
      from spinal cord, caudal NTS, area postrema, VRC, dorsolateral pons, raphe
      nuclei, lateral hypothalamus, central amygdala, and insular cortex. The results
      suggest that 1) whether or not the ML is specialized for CO(2) sensing, its
      complex neuropil likely regulates the activity of RTN chemosensitive neurons; 2)
      the catecholaminergic, cholinergic, and serotonergic innervation of RTN
      represents a possible substrate for the known state-dependent control of RTN
      chemoreceptors; 3) VGLUT3-ir terminals are a probable marker of RTN; and 4) the
      chemosensitive neurons of RTN may provide a chemical drive to multiple
      respiratory outflows, insofar as RTN innervates the entire VRC.

PMID- 16958086
TI  - Differential response of arcuate proopiomelanocortin- and neuropeptide Y
      containing neurons to the lesion produced by gold thioglucose administration.
AB  - The effect of gold thioglucose (GTG) administration on neurons containing feeding
      related peptides in the hypothalamic arcuate nucleus was examined in mice.
      Intraperitoneal GTG injection increased the body weight and produced a
      hypothalamic lesion that extended from the ventral part of the ventromedial
      nucleus to the dorsal part of the arcuate nucleus. Neurons containing
      proopiomelanocortin (POMC) and neuropeptide Y (NPY) present in the dorsal part of
      the arcuate nucleus were destroyed by GTG. In addition, the peptide-containing
      fibers that extended from the remaining arcuate neurons were degenerated at the
      lesion site. The number of POMC-containing fibers in the paraventricular nucleus,
      dorsomedial nucleus, and lateral hypothalamus was found to have decreased
      significantly when examined at 2 days and 2 weeks after the GTG treatment. In
      contrast, the number of NPY-containing fibers in the lateral hypothalamus
      remained unchanged after the GTG treatment, probably because of the presence of
      an unaffected NPY-containing fiber pathway passing through the tuberal region and
      projecting onto the lateral hypothalamus. The number of NPY-immunoreactive fibers
      in the paraventricular and dorsomedial nuclei showed a moderate but significant
      decrease at 2 days after the GTG treatment, but it recovered to the normal levels
      2 weeks later. The NPY-containing fibers were found to have regenerated across
      the lesion site 2 weeks later, and this might contribute to the recovery of the
      NPY-immunoreactive fibers in these regions. The present results first demonstrate
      that POMC- and NPY-containing neurons in the arcuate nucleus respond differently
      to the lesion produced by the GTG treatment.

PMID- 16958087
TI  - The TLR3 ligand polyI: C downregulates connexin 43 expression and function in
      astrocytes by a mechanism involving the NF-kappaB and PI3 kinase pathways.
AB  - Toll-like receptor 3 (TLR3) is a component of the innate immune response that
      responds to dsRNA viruses and virus replication intermediates. In this study we
      show that activation of astrocytes with the dsRNA mimetic polyinosinic-cytidylic
      acid (pI:C) results in loss of expression of connexin43 (Cx43) mRNA and protein
      while upregulating the expression of the ionotropic P2 receptor P2X(4)R. Analysis
      of the signaling pathways involved failed to demonstrate a role for the p38 MAP
      kinase, ERK, or JNK signaling pathways whereas an inhibitor of the PI3 kinase/Akt
      pathway effectively blocked the action of pI:C. Using adenoviral vectors
      containing a super-repressor of NF-kappaB (NF-kappaB SR) construct or a dominant
      negative interferon regulatory factor 3 (dnIRF3) construct showed that inhibition
      of both transcription factors also blocked the effects of pI:C. To explore the
      functional consequences of pI:C activation we used a pore-forming assay for
      P2X(4)R activity and a scrape loading assay for gap junction intercellular
      communication (GJIC). No pore-forming activity consistent with functional P2X(4)R
      expression was detected in either control or activated astrocytes. In contrast,
      robust Lucifer yellow transfer indicative of GJIC was detected in resting cells
      that was lost following pI:C activation. The dnIRF3 construct failed to restore
      GJIC whereas the NF-kappaB SR or the NF-kappaB inhibitor BAY11-7082 and the PI3K
      inhibitor LY294002 all significantly reversed the effect of pI:C on GJ
      connectivity. We conclude that activation of the innate immune response in
      astrocytes is associated with functional loss of GJIC through a pathway involving
      NF-kappaB and PI3 kinase.

PMID- 16958088
TI  - Cellular iron status influences the functional relationship between microglia and
      oligodendrocytes.
AB  - Previously, we have reported that there is a spatiotemporal relationship between
      iron accumulation in microglia and oligodendrocytes during normal development and
      in remyelination following injury. This in vivo observation has prompted us to
      develop a cell culture model to test the relationship between iron status of
      microglia and survival of oligodendrocytes. We found that conditioned media from
      iron-loaded microglia increases the survival of oligodendrocytes; but conditioned
      media from iron loaded activated microglia is toxic to oligodendrocytes. In the
      trophic condition, one of the proteins released by iron-loaded microglia is H
      ferritin, and transfecting the microglia with siRNA for H-ferritin blocks the
      trophic response on oligodendrocytes. Lipopolysaccharide (LPS) activation
      decreases the amount of H-ferritin that is released from microglia and increases
      the release of the proinflammatory cytokines tumor necrosis factor-alpha and
      interleukin-1. LPS activation of iron-enriched microglia results in the
      activation of NF-kB and greater release of cytokines when compared with that of
      control microglia; whereas treating microglia with an iron chelator is associated
      with less NF-kB activation and less release of cytokines. These results indicate
      that microglia play an important role in iron homoeostasis and that their iron
      status can influence how microglia influence growth and survival of
      oligodendrocytes. The results further indicate that ferritin, released by
      microglia, is a significant source of iron for oligodendrocytes.

PMID- 16958090
TI  - Type-2 cells as link between glial and neuronal lineage in adult hippocampal
      neurogenesis.
AB  - In the course of adult hippocampal neurogenesis, new cells go through a series of
      stages associated with proliferative activity. The most highly proliferative cell
      type is an intermediate precursor cell, called type-2 cell. We here report that
      on the level of type-2 cells a transition takes place between features associated
      with the glial and the neuronal lineage. We show that stem-cell marker Sox2 and
      radial glia marker BLBP are expressed in type-2 cells but label only a small
      percentage of the proliferating cells. By and large, precursor cell marker Sox2
      was found to be widely expressed in hippocampal astrocytes. Between 3 h and 1
      week after a single injection of permanent S-phase marker bromodeoxyuridine
      (BrdU), the number of BrdU-labeled BLBP-positive cells did not change, consistent
      with the idea that both markers here are associated with the maintained precursor
      cell pool. Using reporter gene mice expressing the green fluorescent protein
      (GFP) under the promoter for nestin we found an overlap of GFP with markers of
      the neuronal lineage, doublecortin (DCX) and transcription factor NeuroD1 in type
      2 cells, whereas in glial fibrillary acidic protein (GFAP)-GFP mice expression of
      GFP and NeuroD1 or DCX was mutually exclusive. Electrophysiologically, the group
      of type-2 cells fell into two subgroups: one with astrocytic properties and
      another with an early "complex" phenotype of neural progenitor cells. Our data
      further support the existence of proliferative precursor cells that mark the
      transition between glia-like states and neuronal differentiation.

PMID- 16958089
TI  - 5-Hydroxytryptamine-mediated increase in glutamate uptake by the leech giant
      glial cell.
AB  - The clearance of synaptically released glutamate is one of the pivotal functions
      of glial cells. We have studied the role of 5-hydroxytryptamine (5-HT, 30
      microM), a neurotransmitter and neurohormone in the leech central nervous system
      with a versatile action spectrum, on the efficacy of glial glutamate uptake. The
      activity of the glutamate uptake carrier in the giant glial cell in isolated
      ganglia of Hirudo medicinalis was monitored by measuring the membrane current and
      the change in the intracellular Na(+) concentration (Na(+) (i)) as induced by the
      glutamate carrier substrate D-aspartate (D-asp, 1 mM). 5-HT increased the D-asp
      induced current (EC(50) at 5 microM) and rise in Na(+) (i), an effect which was
      mimicked by the membrane-permeable cyclic nucleotide analogue dibutyryl-cyclic
      AMP (db-cAMP). The adenylyl cyclase inhibitor SQ 22,536 and the protein kinase A
      antagonist Rp-cAMP inhibited the effect of 5-HT. Blocking the G protein in the
      giant glial cell by injecting GDP-beta-S suppressed the effect of 5-HT, but not
      the effect of db-cAMP, on the D-asp-induced current. Our results suggest that 5
      HT enhances the glial uptake of glutamate via cAMP- and PKA-mediated pathway.

PMID- 16958091
TI  - Regulation of KCC2 and NKCC during development: membrane insertion and
      differences between cell types.
AB  - The developmental switch of GABA's action from excitation to inhibition is likely
      due to a change in intracellular chloride concentration from high to low. Here we
      determined if the GABA switch correlates with the developmental expression
      patterns of KCC2, the chloride extruder K+-Cl- cotransporter, and NKCC, the
      chloride accumulator Na+-K+-Cl- cotransporter. Immunoblots of ferret retina
      showed that KCC2 upregulated in an exponential manner similar to synaptophysin (a
      synaptic marker). In contrast, NKCC, which was initially expressed at a constant
      level, upregulated quickly between P14 and P28, and finally downregulated to an
      adult level that was greater than the initial phase. At the cellular level,
      immunocytochemistry showed that in the inner plexiform layer KCC2's density
      increased gradually and its localization within ganglion cells shifted from being
      primarily in the cytosol (between P1-13) to being in the plasma membrane (after
      P21). In the outer plexiform layer, KCC2 was detected as soon as this layer
      started to form and increased gradually. Interestingly, however, KCC2 was
      initially restricted to photoreceptor terminals, while in the adult it was
      restricted to bipolar dendrites. Thus, the overall KCC2 expression level in
      ferret retina increases with age, but the time course differs between cell types.
      In ganglion cells the upregulation of KCC2 by itself cannot explain the
      relatively fast switch in GABA's action; additional events, possibly KCC2's
      integration into the plasma membrane and downregulation of NKCC, might also
      contribute. In photoreceptors the transient expression of KCC2 suggests a role
      for this transporter in development.

PMID- 16958092
TI  - Mouse cortical inhibitory neuron type that coexpresses somatostatin and
      calretinin.
AB  - Mammalian cortex contains a diversity of inhibitory neuron types, each with
      distinct morphological, immunochemical, and/or physiological properties. In rat
      cortex, chemical markers distinguish at least four distinct and nonoverlapping
      neuron classes based on expression of parvalbumin (PV), somatostatin (SST),
      calretinin (CR), and cholecystokinin (CCK). It has generally been assumed that
      these classifications should also apply to other rodent species. In mouse cortex,
      however, we found significant colocalization of SST and CR in inhibitory neurons;
      about 30% of SST-positive cells contained CR, and about 33% of CR-positive cells
      contained SST across frontal, somatosensory (S1), and visual cortex (V1). The SST
      and CR colocalized cells were concentrated in layer 2/3. We further characterized
      morphological and physiological properties of the mouse cortical inhibitory
      neuron types that express SST by using "GIN" transgenic mice, in which GFP is
      expressed in a subset of SST inhibitory neurons (see Oliva et al. [2000] J
      Neurosci 20:3354-3368). Generally, both SST/CR+ cells and SST/CR- cells exhibited
      morphological features of Martinotti cells as described in rat cortex, and they
      also had similar accommodating spike-firing patterns. However, they differed
      significantly in quantitative comparisons of morphology and spike shapes. SST/CR+
      cells had more horizontally extended dendritic fields and more primary process
      than did SST/CR- cells; and SST/CR- cells had narrower action potential widths
      and faster afterhyperpolarization than did SST/CR+ cells. Thus, our data show an
      important species difference in the chemical distinction of inhibitory neuron
      subtypes, and indicate that colocalization of CR in SST cells correlates with
      different morphological and physiological features.

PMID- 16958094
TI  - Development of dyskinesias in a 5-year trial of ropinirole and L-dopa.
AB  - A 5-year trial of ropinirole and levodopa in early Parkinson's disease showed
      that ropinirole is associated with reduced incidence of dyskinesias. This post
      hoc analysis investigated whether the dyskinesia-sparing benefit of ropinirole is
      lost when levodopa is added to the regimen and evaluated other risk factors for
      developing dyskinesias. Patients receiving levodopa had a significantly higher
      risk of dyskinesias than those taking ropinirole monotherapy (hazard ratio [HR],
      6.67; 95% confidence interval [CI], 3.23-14.29; P < 0.001). When patients
      randomized to ropinirole were treated with supplementary levodopa, the
      development of dyskinesias was not significantly different from that in those
      receiving levodopa from the start (HR, 0.80; 95% CI, 0.48-1.33; P = 0.39).
      However, the onset of dyskinesias was delayed by around 3 years compared with
      levodopa monotherapy. Adjusted analyses taking into account baseline and on
      treatment factors that influenced use of supplementary levodopa or the
      development of dyskinesias produced similar results. In conclusion, the risk of
      developing dyskinesias during maintained initial ropinirole monotherapy is very
      low. Only once levodopa is added does the risk substantially change. Early use of
      ropinirole postpones the onset of dyskinesias, but these benefits decline when
      levodopa therapy is started, with no evidence of a subsequent rapid "catch-up" or
      a persisting preventive effect.

PMID- 16958095
TI  - Differential specificity in the glomerular response profiles for alicyclic,
      bicyclic, and heterocyclic odorants.
AB  - As part of our ongoing effort to relate stimulus to response in the olfactory
      system, we tested the hypothesis that the unique chemical structures and odors of
      various cyclic odorants would be associated with unique spatial response patterns
      in the glomerular layer of the rat olfactory bulb. To this end, rats were exposed
      to sets of odorants, including monocyclic hydrocarbons, bicyclic compounds, and
      various heterocyclic structures containing oxygen or nitrogen in the ring.
      Relative activity across the entire layer was assessed by mapping uptake of 2
      deoxyglucose into anatomically standardized data matrices. Whereas monocyclic
      hydrocarbons evoked patterns similar to those evoked by open-chained hydrocarbon
      odorants, a set of bicyclic compounds with structures and odors similar to
      camphor evoked uptake in paired ventral domains not previously associated with
      any other odorant chemical structures. Despite their unique odors as judged by
      humans, heterocyclic odorants either evoked uptake in previously characterized
      areas corresponding to their functional groups or stimulated weak or patchy
      patterns involving isolated glomeruli. Although the patchiness of the patterns
      may be partially related to the rigidity of the compounds, which would be
      expected to restrict their interactions to only a few receptors, the weakness of
      the patterns suggests the possibility of species-specific odorant
      representations. We conclude that, whereas some of the novel cyclic structures
      indeed were represented by unique patterns in the rat bulb, other unique
      structures were poorly represented, even when they evoked intense and unique
      odors in humans.

PMID- 16958096
TI  - Clinical phenotype of subjects with Parkinson's disease and orthostatic
      hypotension: autonomic symptom and demographic comparison.
AB  - The objective of this study was to characterize the phenotypic associations of
      orthostatic hypotension (OH) in Parkinson's disease (PD). One hundred fifty-nine
      subjects with PD underwent assessment including autonomic symptom severity
      scoring, disease-specific rating scales, and measurement of postural blood
      pressure response. Symptoms of autonomic impairment weakly correlated with
      disease duration and severity. A posture and gait instability (PIGD) motor
      phenotype was associated with greater severity of autonomic symptoms. Eighty
      subjects (50.3%) had OH. These subjects were older, more likely to be male, and
      taking larger doses of dopaminergic medications than those without OH. There was
      no difference in disease severity or duration between those with and those
      without OH. Symptomatic dizziness did not distinguish between groups, although
      subjects with OH had more symptoms of generalized autonomic impairment than those
      without. Progressive autonomic involvement may be linked to disease progression
      in PD, particularly in patients with a PIGD phenotype, but dichotomization into
      groups with and without OH is a relatively insensitive method for demonstrating
      this. Longitudinal studies of changes in autonomic reflex abnormalities,
      autonomic symptom profiles, and motor severity might clarify these associations.

PMID- 16958097
TI  - Inducible Cre recombinase activity in mouse cerebellar granule cell precursors
      and inner ear hair cells.
AB  - A transgenic mouse line expressing the CreER(TM) fusion protein under the control
      of the Math1 enhancer was generated. Expression of the transgene in the postnatal
      mouse was restricted to hair cells of the inner ear and granule neurons in the
      external granule layer of the cerebellum in a temporally regulated manner. Cre
      activity was virtually nonexistent in uninduced mice; however, treatment of
      newborn pups with tamoxifen, leading to nuclear translocation of the fusion
      protein, resulted in efficient recombination at LoxP sites in the appropriate
      cell types. Up to two thirds of cerebellar granule neurons and 80-90% of cochlear
      hair cells underwent Cre-specific recombination. This mouse line provides a
      powerful tool to dissect gene function at early and late stages in development of
      the cerebellum and inner ear.

PMID- 16958098
TI  - Time-lapse tracing of mitotic cell divisions in the early Xenopus embryo using
      microscopic MRI.
AB  - Mitotic cell division is a highly regulated cellular event in all organisms, but
      its direct visualization in the vertebrates is limited to animals with
      transparent embryos. Here, we report on the use of microscopic magnetic resonance
      imaging (mMRI) to noninvasively observe mitotic cell division of early
      blastomeres in the optically opaque Xenopus laevis embryo. Due to intrinsic
      tissue contrast, cell nuclei can be directly visualized without the need for
      contrast enhancing labeling. By taking two-dimensional in vivo time-lapse image
      sequences, the karyokinesis of a blastomere is followed. Timing and orientation
      of the cleavages can be traced for five cell divisions to establish a cell
      lineage tree, including orientation and timing of the mitosis. This work
      demonstrates for the first time the use of MRI for the visualization of cell
      divisions and expands the experimental scope of the Xenopus embryo.

PMID- 16958099
TI  - Co-occurrence of calcium-binding proteins and calcium-permeable glutamate
      receptors in the primary gustatory nucleus of goldfish.
AB  - Primary vagal gustatory afferents utilize glutamate as a neurotransmitter acting
      on AMPA/kainate receptors of second-order neurons. Some forms of ionotropic
      glutamate receptors permit passage of Ca++ ions upon activation by appropriate
      ligands. Calcium-binding proteins (CaBPs) play a buffering role for regulating
      the concentration of intracellular calcium. In the present study, we used
      immunohistochemistry to examine the distribution and morphology of neurons with
      CaBPs, including calretinin, calbindin, and parvalbumin, and to compare this
      distribution with neurons exhibiting Ca++-permeable glutamate receptors as
      determined by kainate-stimulated uptake of Co++ in the vagal lobe of goldfish.
      Calretinin- and calbindin-positive neurons occurred throughout the sensory zone
      including round unipolar, horizontal; and perpendicular bipolar or multipolar
      somata. Parvalbumin neurons were mainly round monopolar neurons, especially
      common in the superficial layers of the sensory zone. In the motor zone, while
      parvalbumin labeled nearly all motoneurons, calretinin labeled only external
      motoneurons. In double labeling with calretinin and parvalbumin, few neurons in
      the sensory layer labeled with both antisera. Immunocytochemistry following
      kainate-stimulate uptake of Co++ showed that most calretinin, but few parvalbumin
      immunopositive neurons also were labeled by cobalt in the central and deep layers
      of the sensory zone. All motoneurons were labeled by Co++, including those
      immunoreactive for calretinin or parvalbumin. These results indicate that
      calretinin expression is strongly correlated with calcium-permeable ionotropic
      glutamate receptors in the neurons of the sensory zone of the goldfish vagal
      lobe, but even within this limited region, not all Ca++-permeable neurons possess
      any of the CaBPs examined.

PMID- 16958100
TI  - Functional analysis of lung tumor suppressor activity at 3p21.3.
AB  - The early and frequent occurrence of deletions at 3p21.3 in lung cancer has led
      to the consideration of this chromosomal region as a lung cancer (LUCA) critical
      region with tumor suppressor activity. We covered this 19 genes-containing region
      with overlapping P1 artificial chromosomes (PACs), in which genes are likely
      accompanied by their own promoters or other regulatory sequences. With these PACs
      we transfected cells from a small cell lung cancer (SCLC) cell line which readily
      caused tumors in nude mice. Per PAC we selected two cell clones with a low number
      of PAC copies integrated at a single genomic site. The selected clones were s.c.
      injected into nude mice to investigate whether the integrated genes suppressed
      the tumor-inducing capacity of the original SCLC cell line. We could demonstrate
      PAC-specific gene expression in the transfected cells. All of the PAC integration
      sites were different. It appeared that introduction of a PAC or even an empty PAC
      vector causes some chromosomal instability, which in principle may either promote
      or inhibit cell growth. However, both cell clones with integration of the same
      PAC from the centromeric part of the LUCA region in different genomic sites were
      the sole pair of clones that caused smaller tumors than did the original SCLC
      cell line. This suggests that rather than the induced chromosomal instability,
      the DNA sequence of that PAC, which in addition to two protein-encoding genes
      contains at least one potential miRNA gene, is responsible for the tumor
      suppressor activity.

PMID- 16958101
TI  - Developmental expression of the chick four-jointed homologue.
AB  - Four-jointed is a type II transmembrane protein that is thought to be cleaved to
      give rise to a secreted protein. In Drosophila, four-jointed controls outgrowth,
      vein patterning, and bristle polarity in the developing limb together with the
      polarity of the ommatidia in the developing eye. In Drosophila and mice, Fj is
      regulated by notch signaling. Here, we have determined the expression of the
      chick four-jointed (fjx) homologue during embryonic development. We show that fjx
      is expressed in the limb bud; facial primordia; the proliferating zone of the
      lens, feather buds, the neural tube; and neural crest derivatives such as the
      dorsal root ganglia. Analysis of the fjx expression in the developing limb bud
      showed that initially fjx is expressed throughout the limb bud, but as the limb
      develops, highest levels of fjx transcripts are found distally. However, by stage
      27, fjx expression is predominantly found in the central core of the limb bud.
      Finally, fjx expression becomes confined to the developing tendons, ligaments,
      articular cartilage, and arteries but not the veins. Comparison with scleraxis
      (scx), a marker of tendons and ligaments, revealed that they are coexpressed in
      the majority of tendons but that fjx is expressed after scx, when the tendons
      have begun to differentiate. These data suggest that fjx has two roles during
      limb development: the first controlling outgrowth and the second tissue
      differentiation.

PMID- 16958102
TI  - Oligonucleotide array-based comparative genomic hybridization (aCGH) of 90
      neuroblastomas reveals aberration patterns closely associated with relapse
      pattern and outcome.
AB  - The study of genomic alterations in neuroblastoma is of particular importance
      since several cytogenetic markers proved to be closely associated with the
      clinical phenotype. To disclose patterns of gains and losses, we performed high
      resolution oligonucleotide array-based comparative genomic hybridization (aCGH).
      A total cohort of 90 patients was classified into 6 subsets according to tumor
      stage and outcome: Stages 1-3+ (with event), Stage 1-3- (no event), Stage 4+/-,
      and Stage 4S+/-. The aberration patterns in Stages 1-3- and 4S- tumors differed
      from all other groups as they were predominantly characterized by losses (3, 4,
      14, X) and gains (7, 17) of whole chromosomes. However, 59/65 (91%) tumors of
      Stages 1-3+ or Stage 4 revealed numerous structural copy number alterations
      (sCNA). While deletions in chromosomes 1, 3, and 11 discriminated outcome in
      Stage 4, there were no specific sCNA that distinguished tumor stage within the
      subgroup of unfavorable tumors. sCNA in 1p, 3p, 11q, 17q, or MYCN amplification
      (MNA) was seen among 22/24 patients who died, 10/12 with metastatic relapses, and
      5/9 with local recurrences. Detailed breakpoint analyses on chromosomes 1, 3, 11,
      and 17 disclosed preferred breaking areas, although breakpoints were not
      identical. Amplifications were found in 18 patients and involved 2p24 (MYCN) and
      other segments of chromosome 2, as well as regions on chromosome arms 6q, 12q,
      and 17q. One single feature in 21q21.1 (BU678720, without known function yet)
      attracted particular attention since five patients showed a homozygous loss of
      this sequence.

PMID- 16958103
TI  - Sp5l is a mediator of Fgf signals in anteroposterior patterning of the
      neuroectoderm in zebrafish embryo.
AB  - The neuroectoderm is patterned along the anterior-posterior axis in vertebrate
      embryos. Fgf signals are required to induce the posterior neuroectodermal fates,
      but they repress the anterior fate. Sp5l/Spr2, an Sp1-like transcription factor
      family member, has been shown to be required for development of mesoderm and
      posterior neuroectoderm. We demonstrate here that repression of the anterior
      neuroectodermal markers fez and otx1 by fgf17b or fgf3 coincides with induction
      of sp5l in the anterior neuroectoderm, and that this repression is efficiently
      rescued by simultaneous sp5l knockdown. On the other hand, sp5l knockdown is able
      to inhibit inductive activity of ectopic Fgf signals on the expression of the
      posterior neuroectodermal markers gbx2, hoxb1b, and krox20. Furthermore, effect
      of overexpression of a dominant negative Fgf receptor on anteroposterior
      patterning of the neuroectoderm is rescued by sp5l overexpression. Taken
      together, these data suggest that sp5l mediates the functions of Fgf signals in
      anteroposterior patterning of the neuroectoderm during zebrafish embryogenesis.

PMID- 16958104
TI  - Axotomy induces contrasting changes in calcium and calcium-binding proteins in
      oculomotor and hypoglossal nuclei of Balb/c mice.
AB  - Motor neurons with different susceptibility to degeneration have been identified
      in amyotrophic lateral sclerosis (ALS). Increase of intracellular calcium has
      been proposed as a mediator, amplifying the damage through a positive feedback of
      the known pathological processes. Accordingly, the potential of motor neurons to
      limit calcium increases during injury might be proportional to their viability. A
      basic mechanism of reducing calcium amplitudes depends on the calcium-buffering
      capacity, determined by the calcium-binding protein content. In this study,
      oculomotor and hypoglossal neurons, prototypes of resistant and vulnerable motor
      neurons in ALS were examined in axotomy experiments. Total calcium-, parvalbumin
      , and calbindin-D28k levels of motor neurons of adult mice were characterized by
      electron microscopic histochemistry and light microscopic immunostaining. In
      hypoglossal neurons, compared with oculomotor neurons, larger and more enduring
      increases of calcium were detected. The perikarya of hypoglossal neurons remained
      immunonegative for both parvalbumin and calbindin-D28k. Qualitatively, no major
      cell loss was noted after axotomy, but a decreased neuronal marker staining at
      days 1-14 suggested a reversible injury of hypoglossal neurons. Oculomotor
      neurons were not stained for calbindin-D28k but stained for parvalbumin in
      control conditions, staining which increased at postoperative days 7-14 before
      returning to baseline. Neuronal marker staining did not change in these cells
      during the observed period. The higher level of parvalbumin in resistant motor
      neurons and their ability to up-regulate parvalbumin after injury, paralleled by
      a smaller increase of intracellular calcium suggest that parvalbumin may have a
      protective effect in these cells.

PMID- 16958105
TI  - Gangliogenesis in the enteric nervous system: roles of the polysialylation of the
      neural cell adhesion molecule and its regulation by bone morphogenetic protein-4.
AB  - The neural crest-derived cells that colonize the fetal bowel become patterned
      into two ganglionated plexuses. The hypothesis that bone morphogenetic proteins
      (BMPs) promote ganglionation by regulating neural cell adhesion molecule (NCAM)
      polysialylation was tested. Transcripts encoding the sialyltransferases, ST8Sia
      IV (PST) and ST8Sia II (STX), which polysialylate NCAM, were detectable in fetal
      rat gut by E12 but were downregulated postnatally. PSA-NCAM-immunoreactive neuron
      numbers, but not those of NCAM, were developmentally regulated similarly.
      Circular smooth muscle was transiently (E16-20) PSA-NCAM-immunoreactive when it
      is traversed by migrating precursors of submucosal neurons. Neurons developing in
      vitro from crest-derived cells immunoselected at E12 with antibodies to p75(NTR)
      expressed NCAM and PSA-NCAM. BMP-4 promoted neuronal NCAM polysialylation and
      clustering. N-butanoylmannosamine, which blocks NCAM polysialylation, but not N
      propanoylmannosamine, which does not, interfered with BMP-4-induced neuronal
      clustering. Observations suggest that BMP signaling enhances NCAM
      polysialylation, which allows precursors to migrate and form ganglionic
      aggregates during the remodeling of the developing ENS.

PMID- 16958106
TI  - Topography of cortical projections to the dorsolateral neostriatum in rats:
      multiple overlapping sensorimotor pathways.
AB  - In rodents, the whisker representation in primary somatosensory (SI) cortex
      projects to the dorsolateral neostriatum, but the location of these projections
      has never been characterized with respect to layer IV barrels and their
      intervening septa. To address this issue, we injected a retrograde tracer into
      the dorsolateral neostriatum and then reconstructed the location of the labeled
      corticostriatal neurons with respect to the cytochrome oxidase (CO)-labeled
      barrels in SI. When the tracer was restricted to a small focal site in the
      neostriatum, the retrogradely labeled neurons formed elongated strips that were
      parallel to the curvilinear orientation of layer IV barrel rows. After larger
      tracer injections, labeled neurons were distributed uniformly across layer V and
      were aligned with both the barrel and septal compartments. Labeled projections
      from the contralateral SI barrel cortex, however, were much fewer in number and
      were disproportionately associated with the septal compartments. A comparison of
      the labeling patterns in the ipsilateral and contralateral hemispheres revealed
      symmetric, mirror-image distributions that extended across primary motor cortex
      (MI) and multiple somatosensory cortical regions, including the secondary
      somatosensory (SII) cortex, the parietal ventral (PV) and parietal rhinal (PR)
      areas, and the posteromedial (PM) region. Examination of the thalamus revealed
      labeled neurons in the intralaminar nuclei, in the medial part of the posterior
      nucleus (POm), and in the ventrobasal complex. These results indicate that the
      dorsolateral neostriatum integrates sensorimotor information from multiple
      sensorimotor representations in the thalamus and cortex.

PMID- 16958107
TI  - Afferents of the lamprey optic tectum with special reference to the GABA input:
      combined tracing and immunohistochemical study.
AB  - The optic tectum in the lamprey midbrain, homologue of the superior colliculus in
      mammals, is important for eye movement control and orienting responses. There is,
      however, only limited information regarding the afferent input to the optic
      tectum except for that from the eyes. The objective of this study was to define
      specifically the gamma-aminobutyric acid (GABA)-ergic projections to the optic
      tectum in the river lamprey (Lampetra fluviatilis) and also to describe the
      tectal afferent input in general. The origin of afferents to the optic tectum was
      studied by using the neuronal tracer neurobiotin. Injection of neurobiotin into
      the optic tectum resulted in retrograde labelling of cell groups in all major
      subdivisions of the brain. The main areas shown to project to the optic tectum
      were the following: the caudoventral part of the medial pallium, the area of the
      ventral thalamus and dorsal thalamus, the nucleus of the posterior commissure,
      the torus semicircularis, the mesencephalic M5 nucleus of Schober, the
      mesencephalic reticular area, the ishtmic area, and the octavolateral nuclei.
      GABAergic projections to the optic tectum were identified by combining
      neurobiotin tracing and GABA immunohistochemistry. On the basis of these double
      labelling experiments, it was shown that the optic tectum receives a GABAergic
      input from the caudoventral part of the medial pallium, the dorsal and ventral
      thalamus, the nucleus of M5, and the torus semicircularis. The afferent input to
      the optic tectum in the lamprey brain is similar to that described for other
      vertebrate species, which is of particular interest considering its position in
      phylogeny.

PMID- 16958108
TI  - cDNA cloning of myosin heavy chain genes from medaka Oryzias latipes embryos and
      larvae and their expression patterns during development.
AB  - Several sarcomeric myosin heavy chains (MYHs) were cloned from embryos and larvae
      of medaka Oryzias latipes. Three genes encoding medaka MYHs (mMYHs) predominantly
      expressed in embryos (mMYH(emb1)) and larvae (mMYH(L1) and mMYH(L2)), all
      belonged to fast skeletal MYHs, showing spatiotemporally different expression
      patterns during development. Besides these mMYHs, a few novel mMYHs were cloned
      from embryos and larvae at hatching. Whereas mMYH(emb2), mMYH(emb3), and mMYH(L3)
      belonged to fast skeletal MYH, mMYH(C1) and mMYH(C2) did to slow/cardiac MYH.
      mMYH(emb1) was expressed ahead of mMYH(L1) and mMYH(L2). In situ hybridization
      analysis demonstrated that the transcripts of mMYH(emb1) and mMYH(C1) were
      located in the horizontal myoseptum, whereas those of mMYH(L1) and mMYH(L2) in
      the inner part of myotomes and pharyngeal muscles, and those of mMYH(C2) in the
      heart rudiment. In silico cloning based on the medaka genome database showed
      another mMYHs of the slow/cardiac types, mMYH(C3) and mMYH(C4).

PMID- 16958109
TI  - Differential expression of muscarinic acetylcholine receptors across excitatory
      and inhibitory cells in visual cortical areas V1 and V2 of the macaque monkey.
AB  - Cholinergic neuromodulation, a candidate mechanism for aspects of attention, is
      complex and is not well understood. Because structure constrains function,
      quantitative anatomy is an invaluable tool for reducing such a challenging
      problem. Our goal was to determine the extent to which m1 and m2 muscarinic
      acetylcholine receptors (mAChRs) are expressed by inhibitory vs. excitatory
      neurons in the early visual cortex. To this end, V1 and V2 of macaque monkeys
      were immunofluorescently labelled for gamma-aminobutyric acid (GABA) and either
      m1 or m2 mAChRs. Among the GABA-immunoreactive (ir) neurons, 61% in V1 and 63% in
      V2 were m1 AChR-ir, whereas 28% in V1 and 43% in V2 were m2 AChR-ir. In V1, both
      mAChRs were expressed by fewer than 10% of excitatory neurons. However, in V2,
      the population of mAChR-ir excitatory neurons was at least double that observed
      in V1. We also examined m1 and m2 AChR immunoreactivity in layers 2 and 3 of area
      V1 under the electron microscope and found evidence that GABAergic neurons
      localize mAChRs to the soma, whereas glutamatergic neurons expressed mAChRs more
      strongly in dendrites. Axon and terminal labelling was generally weak. These data
      represent the first quantitative anatomical study of m1 and m2 AChR expression in
      the cortex of any species. In addition, the increased expression in excitatory
      neurons across the V1/V2 border may provide a neural basis for the observation
      that attentional effects gain strength up through the visual pathway from area V1
      through V2 to V4 and beyond.

PMID- 16958110
TI  - A homologue of snail is expressed transiently in subsets of mesenchyme cells in
      the sea urchin embryo and is down-regulated in axis-deficient embryos.
AB  - Vertebrate members of the zinc finger transcription factor family related to
      Drosophila snail are expressed in neural crest and paraxial mesoderm along the
      left-right axis of the embryo. As simple deuterostomes, echinoderms are an
      important sister phylum for the chordates. We have identified populations of
      patterned, nonskeletogenic mesenchyme in the sea urchin Lytechinus variegatus by
      their expression of a sea urchin member of the snail family (Lv-snail). Lv-snail
      mRNA and protein are detectable at the midgastrula stage within the archenteron.
      At the late gastrula stage, a contiguous cluster of cells on the left side of the
      tip of the archenteron is Lv-snail-positive. At the early prism stage, two small
      clusters of mesenchyme cells near the presumptive arm buds are also Lv-snail
      positive. At the pluteus stage, staining is detectable in isolated mesenchyme
      cells and the ciliated band. Based on fate mapping of secondary mesenchyme cells
      (SMCs) and double-label immunostaining, these patterns are consistent with
      expression of SNAIL by novel subsets of SMCs that are largely distinct from
      skeletogenic mesenchyme. In radialized embryos lacking normal bilateral symmetry,
      mesenchymal expression of Lv-SNAIL is abolished. These results suggest that
      transient expression of Lv-snail may be important for the differentiation of a
      subset of axially patterned nonskeletogenic mesenchyme cells and suggest
      conserved functions for snail family members in deuterostome development.

PMID- 16958111
TI  - Symptom severity in obese women with binge eating disorder as a function of
      smoking history.
AB  - OBJECTIVE: To compare obese female former smokers with binge eating disorder
      (BED) to women with BED with no smoking history in the severity of binge eating
      and associated symptoms. METHOD: A consecutive series of 91 obese women with
      current diagnoses of BED were administered structured diagnostic and investigator
      based interviews and self-report questionnaires to assess symptoms associated
      with eating disorders. Participants were classified as "never" or "former"
      smokers and symptom profiles were compared across smoking groups. RESULTS: Former
      and never-smoking groups did not differ in age, body mass index, or current binge
      frequency. Former smokers reported significantly higher levels of dietary
      restraint, rigid dieting strategies, and avoidance of eating. CONCLUSION: Former
      smokers were significantly more likely than never-smokers to endorse specific
      symptoms of eating pathology (i.e., rigid dieting strategies). Despite the
      average 15-year interval since smoking cessation, the former smokers in this
      patient group resembled current smokers with other eating disorders in terms of
      rigid and restrictive weight control methods. Obese patients with a smoking
      history may benefit from treatment to address rigid/pathological dieting and
      strategies.

PMID- 16958112
TI  - Alteration of cystatin C in the cerebrospinal fluid of multiple sclerosis.
AB  - The protein profiles in the cerebrospinal fluid of 10 patients with multiple
      sclerosis (MS), 10 patients with neuromyelitis optica (NMO), 8 inflammatory
      disease control patients, and 4 noninflammatory disease control patients were
      screened by surface-enhanced laser desorption/ionization time-of-flight mass
      spectrometry. Peaks of 12.5 kDa were significantly lower in multiple sclerosis,
      NMO, and inflammatory disease control patients than in noninflammatory disease
      control patients, and 13.4 kDa peaks were higher in NMO than in inflammatory
      disease control patients. Further analyses demonstrated that both peaks were
      cystatin C. Enzyme-linked immunosorbent assay showed that the cystatin C levels
      tended to be lower in multiple sclerosis and NMO. Alterations of cystatin C may
      relate to the pathogeneses of demyelinating diseases.

PMID- 16958113
TI  - Delayed Nogo receptor therapy improves recovery from spinal cord contusion.
AB  - OBJECTIVE: Myelin-associated inhibitors play a role in limiting axonal growth in
      the adult central nervous system. Blocking these inhibitors may promote
      neurological recovery from spinal cord contusion. METHODS: The soluble Nogo-66
      receptor (NgR(310)ecto-Fc) protein, which can neutralize three myelin inhibitors,
      was infused into rats after spinal cord contusion for 28 days. Treatment was
      initiated intrathecally at the time of injury or 3 days after injury by the
      intracerebroventricular route at a dose of 0.29 mg/kg/day. Recovery of locomotion
      and of axonal growth was assessed. Some animals received combination therapy with
      NgR(310)ecto-Fc plus rolipram, a cyclic adenosine monophosphate phosphodiesterase
      inhibitor. RESULTS: Seven weeks after spinal injury, the Basso-Beattie Bresnahan
      locomotor scores were significantly improved in the 3-day delayed NgR(310)ecto-Fc
      treatment group (9.5 +/- 0.7; n = 16) versus the vehicle-treated group, (6.75 +/-
      0.7; n = 15) (p < or = 0.01, analysis of variance). The percentage of
      NgR(310)ecto-Fc-treated animals able to support their weight was twice that in
      the control group. Delayed therapy was as efficacious as acute therapy. Addition
      of rolipram did not alter recovery. The beneficial behavioral effects of
      NgR(310)ecto-Fc correlated with sprouting of raphespinal axons in the caudal
      spinal cord and of corticospinal axons in the rostral spinal cord.
      INTERPRETATION: NgR(310)ecto-Fc treatment improves outcome in a rodent model that
      closely mimicked human spinal cord injury.

PMID- 16958114
TI  - Expression of hedgehog signalling components in adult mouse testis.
AB  - Hedgehog (Hh) signalling is known to regulate many aspects of normal development
      as well as being upregulated in various cancers. Signalling is mediated by the
      Gli family of zinc finger transcription factors. Based on observations that
      deletion of one of the three Hh genes, Dhh, leads to male infertility, we
      hypothesized that regulated expression of Hh signalling components would be a
      feature of adult spermatogenesis. We used in situ hybridization to characterise
      Gli gene expression in juvenile and adult mouse testes. In the first wave of
      spermatogenesis, mRNAs encoding all three Glis are detected in spermatogonia and
      Sertoli cells. In adult mouse testes, these transcripts are observed in
      spermatogonia and spermatocytes, with reduced signal intensity in round
      spermatids. The mRNAs encoding key effectors of Hh signalling, Ptc2, Smo, and Fu,
      are also most apparent in spermatogonia, spermatocytes, and to a lower extent in
      round spermatids. In contrast, mRNA encoding SuFu, a negative regulator of Hh
      signalling, was most predominant in round spermatids and the protein is evident
      in round and elongating spermatids, suggesting that SuFu protein may switch off
      Hh signalling in haploid germ cells. Overall, the coordinated expression pattern
      of these genes in adult mouse testis indicates a role for Hh signalling in
      spermatogenesis.

PMID- 16958115
TI  - Carbohydrate mimics promote functional recovery after peripheral nerve repair.
AB  - OBJECTIVE: The outcome of peripheral nerve repair is often unsatisfactory, and
      efficient therapies are not available. We tested the therapeutic potential of
      functional mimics of the human natural killer cell glycan (3-sulfoglucuronyl
      beta1-3 galactoside) (HNK-1) epitope, a carbohydrate indicated to favor
      specificity of motor reinnervation in mice. METHODS: We applied a linear HNK-1
      mimic peptide, scrambled peptide, or vehicle substances in polyethylene cuffs
      used to reconstruct the severed femoral nerves of adult mice. We used video-based
      motion analysis and morphological and tracing techniques to monitor the outcome
      of nerve repair. RESULTS: After glycomimetic application, quadriceps muscle
      function recovered to 93% of normal within 3 months. Restoration of function was
      less complete (71-76%) in control groups. Better functional recovery was
      associated with larger motoneuron somata, better axonal myelination in the
      quadriceps nerve, and enhanced precision of target reinnervation. Lesion-induced
      death of motoneurons was reduced by 20 to 25%. The glycomimetic enhanced survival
      and neurite outgrowth of both mouse and human motoneurons in vitro by 30 to 75%.
      Application of a novel cyclic glycomimetic also enhanced functional recovery in
      vivo. INTERPRETATION: The improved outcome of nerve repair after glycomimetic
      application may be attributed to neurotrophic effects. Our results hold promise
      for therapeutic use in humans.

PMID- 16958116
TI  - Facets of acculturation and their diverse relations to body shape concern in
      Fiji.
AB  - OBJECTIVE: The present study examines the relation between acculturation and body
      shape concern in Fiji--a society undergoing rapid social change. METHOD: Data
      were from two cohorts of ethnic Fijian girls and women collected in 1998 (n =
      115). A factor analysis was performed to identify dimensions of acculturation.
      The association of these with body shape concern was examined with linear
      regression. RESULTS: Three dimensions of acculturation were identified. Multiple
      linear regression models demonstrated that each of these dimensions of
      acculturation had a unique relation to body shape concern. The adjusted R(2) for
      the fully adjusted model relating acculturation to body concern was 0.63,
      indicating a substantial degree of shared variation between measures of body
      shape concern and measures of acculturation. CONCLUSION: Acculturation may have a
      strong impact on body shape concern in Fiji. However, acculturation is a
      multidimensional construct and does not likely have a monolithic relation to body
      shape concern.

PMID- 16958117
TI  - Physical activity and its correlates in treatment-seeking obese patients with
      binge eating disorder.
AB  - OBJECTIVE: This study examined the physical activity levels reported by obese
      individuals with binge eating disorder (BED), as well as the relationships
      between physical activity and body mass index (BMI), features of eating
      disorders, and associated psychological variables. METHOD: A series of 166 obese
      treatment-seeking adults (121 women and 45 men) with BED were administered
      structured diagnostic interviews and self-report questionnaires. RESULTS: This
      clinical group was found to be extremely sedentary. Self-reported physical
      activity levels, measured by the Paffenbarger Physical Activity Questionnaire,
      were comparable with those reported by obese samples with or without binge eating
      in other studies, but were considerably lower than those reported by a community
      sample. Lifestyle physical activity (e.g., amounts of walking and stair climbing)
      and sports and recreational physical activity were unrelated to most clinical
      characteristics. BMI was significantly, albeit weakly, associated with reported
      sports and recreational activities in women, but not in men. CONCLUSION: Our
      findings highlight the degree to which obese patients with BED are inactive.
      Physical activity was largely uncorrelated with measures of eating disorder and
      psychological functioning in both men and women but was significantly, but
      weakly, correlated with BMI in women. Additional research is needed to determine
      the clinical value of physical activity for this patient group.

PMID- 16958118
TI  - A retrospective comparison of purging type disorders: eating disorder not
      otherwise specified and bulimia nervosa.
AB  - OBJECTIVE: In light of recent research indicating the clinical significance of
      eating disorder not otherwise specified-purging only (EDNOS-P), differences
      between women with lifetime bulimia nervosa purging subtype (BN-P) and EDNOS-P
      were examined. METHOD: Three groups of women were examined, a control group (n =
      684) and two groups with lifetime eating disorders: BN-P (n = 22), and EDNOS-P (n
      = 53). RESULTS: Women with lifetime BN-P were significantly more likely to use
      vomiting than women with EDNOS-P but the latter group relied more on laxative
      abuse. Compared with controls, women with both eating disorders had higher weight
      and shape concern, dietary restraint, lifetime major depression, and suicidality.
      The BN-P group had significantly higher eating concern, dietary restraint, and
      suicidality than the EDNOS-P group. CONCLUSION: In accordance with previous
      research examining women with current eating disorders, EDNOS-P is indicated to
      be clinically significant. On the whole, the pattern of results indicated that
      EDNOS-P lies somewhere between BN-P and healthy controls in its clinical
      significance.

PMID- 16958119
TI  - Primary body axes of vertebrates: generation of a near-Cartesian coordinate
      system and the role of Spemann-type organizer.
AB  - A rationale for the complex-appearing generation of the primary body axes in
      vertebrates can be obtained if this process is divided into two parts. First, an
      ancestral system is responsible for the anteroposterior (AP) patterning of the
      brain and the positioning of the heart. The blastopore (marginal zone) acts as a
      source region that generates primary AP-positional information for the brain, a
      process that is largely independent of the organizer. This evolutionary old
      system was once organizing the single axis of radial-symmetric ancestors. Second,
      the trunk is assumed to be an evolutionary later addition. The AP organization of
      the trunk depends on a time-controlled posterior transformation in which an
      oscillation plays a crucial role. This oscillation also leads to the repetitive
      nature of the trunk pattern as seen in somites or segments. The function of the
      Spemann-type organizer is not to specify the dorsoventral (DV) positional
      information directly but to initiate the formation of a stripe-shaped midline
      organizer, realized with different structures in the brain and in the trunk
      (prechordal plate vs. notochord). The distance of the cells to this midline
      (rather than to the organizer) is crucial for the DV specification. The basically
      different modes of axes formation in vertebrates and insects is proposed to have
      their origin in the initial positioning of the mesoderm. Only in vertebrates the
      mesoderm is initiated in a ring at a posterior position. Thus, only in
      vertebrates complex tissue movements are required to transform the ring-shaped
      posterior mesoderm into the rod-shaped axial structures.

PMID- 16958120
TI  - Evaluating binge eating disorder in children: development of the children's binge
      eating disorder scale (C-BEDS).
AB  - OBJECTIVE: Binge eating disorder (BED) may manifest itself differently in
      children than adults. Recently researchers have proposed provisional criteria for
      measuring BED in children. The purpose of this study was to develop a brief,
      simple, structured, interviewer-administered scale (C-BEDS) to measure BED in
      children according to the provisional criteria and to compare diagnostic results
      with SCID diagnoses. METHOD: A total of 55 children between the ages of 5 and 13
      were interviewed with both the SCID and the C-BEDS. RESULTS: There was a
      significant association between the two measures (p = .001). Both measures
      adequately identified children with binge eating behaviors. CONCLUSION: Both the
      provisional criteria and the C-BEDS may be developmentally appropriate for use
      with children, although the C-BEDS may be a better screening instrument as it
      quickly identified children with subsyndromal BED. If used by physicians and
      other health providers, this brief measure may assist with identifying early
      onset binge eating behaviors and avoiding the associated consequences, including
      adult BED, obesity, and other comorbidities.

PMID- 16958121
TI  - Dexamethasone and long-term outcome in adults with bacterial meningitis.
AB  - OBJECTIVE: This follow-up study of the European Dexamethasone Study was designed
      to examine the potential harmful effect of adjunctive dexamethasone treatment on
      long-term neuropsychological outcome in adults with bacterial meningitis.
      METHODS: Neurological, audiological, and neuropsychological examinations were
      performed in adults who survived pneumococcal or meningococcal meningitis.
      RESULTS: Eighty-seven of 99 (88%) eligible patients were included in the follow
      up study; 46 (53%) were treated with dexamethasone and 41 (47%) with placebo.
      Median time between meningitis and testing was 99 months. Neuropsychological
      evaluation showed no significant differences between patients treated with
      dexamethasone and placebo. The proportions of patients with persisting
      neurological sequelae or hearing loss were similar in the dexamethasone and
      placebo groups. The overall rate of cognitive dysfunction did not differ
      significantly between patients and control subjects; however, patients after
      pneumococcal meningitis had a higher rate of cognitive dysfunction (21 vs 6%; p =
      0.05) and experienced more impairment of everyday functioning due to physical
      problems (p = 0.05) than those after meningococcal meningitis. INTERPRETATION:
      Treatment with adjunctive dexamethasone is not associated with an increased risk
      for long-term cognitive impairment. Adults who survive pneumococcal meningitis
      are at significant risk for long-term neuropsychological abnormalities.

PMID- 16958122
TI  - Segmental expression of the T-box transcription factor, Tbx2, during early
      somitogenesis.
AB  - Tbx2 belongs to the T-box transcription factor gene family and is expressed in a
      variety of tissues and structures throughout development, although not all
      expression domains have been thoroughly described. Two areas of segmented
      expression along the rostral-caudal axis of E10.5-11.5 embryos were identified as
      inter-somitic vessels and dorsal root ganglia. In addition, Tbx2 expression is
      observed during somitogenesis beginning at E9.5, both in the posterior half of
      prospective somites and in a progressively restricted pattern in recently formed
      somites.

PMID- 16958123
TI  - Multiple system atrophy is distinguished from idiopathic Parkinson's disease by
      the arginine growth hormone stimulation test.
AB  - OBJECTIVE: Multiple system atrophy (MSA) may be difficult to distinguish from
      idiopathic Parkinson's disease (PD). Our aim was to evaluate the accuracy of the
      arginine growth hormone (GH) stimulation test in distinguishing between MSA and
      PD in large populations of patients. METHODS: We measured the GH response to
      arginine in 69 MSA (43 MSAp [parkinsonism as the main motor feature] and 26 MSAc
      [cerebellar features predominated]) patients, 35 PD patients, and 90 healthy
      control subjects. We used receiver-operating curve analysis to establish the
      arginine cutoff value that best differentiated between MSA and PD. RESULTS: The
      GH response to arginine was significantly lower (p < 0.01) in MSA than in either
      PD patients or control subjects. At a cutoff level of 4 microg/L, arginine
      distinguished MSAp from PD with a sensitivity and specificity of 91% and MSAc
      from PD with a sensitivity of 96% and specificity of 91%. The arginine test had a
      positive predictive value for MSA of 95%. The GH response to arginine was not
      affected by disease duration or severity, MSA motor subtype, pyramidal signs,
      response to dopaminergic therapy, or magnetic resonance imaging findings.
      INTERPRETATION: The GH response to arginine differentiates MSA from PD with a
      high diagnostic accuracy. The results suggest an impairment of cholinergic
      central systems modulating GH release in MSA.

PMID- 16958124
TI  - Cultural correlates of eating attitudes: a comparison between native-born and
      immigrant university students in Israel.
AB  - OBJECTIVE: This study explores the association between gender and exposure to
      Western culture and attitudes toward eating. METHOD: Four hundred and ninety-nine
      university students participated in the study: 216 Israeli natives, 153 new
      immigrants (3 years or less since immigration) from the Former Soviet Union
      (FSU), and 130 veteran immigrants from FSU (4-15 years since immigration).
      Attitudes toward eating were measured using the Eating Attitude Test - EAT-26.
      RESULTS: Israeli born women had higher weight and body mass index (BMI) than did
      new immigrant women. Higher scores on the EAT-26 were found among women than
      among men. Among women only, native-born Israelis and veteran immigrants were
      more likely to have positive EAT-26 scores (19.6%, 18.8%) than were new immigrant
      women (7.9%), indicating disordered eating attitudes. Part of the differences in
      EAT-26 scores was explained by differences between the groups on age and BMI;
      however, even after adjustment the differences remained significant on the
      bulimia subscale. CONCLUSION: The results suggest a rapid cultural effect in
      attitudes toward eating that may reflect a tendency toward eating disorders as
      well as a difference in the proportion of obesity. It seems that the veteran
      immigrants have adopted Western cultural norms and eating patterns in a way that
      has erased the differences in tendency toward eating disorders between them and
      the Israeli born women.

PMID- 16958125
TI  - Relationships between perfectionism and specific disordered eating behaviors.
AB  - OBJECTIVE: Perfectionism has been reported as a specific risk factor for anorexia
      nervosa and bulimia nervosa, but not binge eating disorder. This study examined
      whether these differences are due to differential associations between
      perfectionism and specific eating disorder behaviors. METHOD: Participants (N =
      2,482) completed the eating disorders inventory perfectionism scale and a
      questionnaire assessing eating disorder symptoms. RESULTS: Perfectionism was
      associated with an array of disordered eating behaviors in women. However,
      associations were strongest for fasting and purging. Further, the association
      between binge eating and perfectionism was statistically mediated by fasting. In
      men, perfectionism was significantly associated only with fasting, and this
      association was greater than associations with other disordered eating behaviors.
      CONCLUSION: Results explain why previous studies have reported weak or
      inconsistent associations between perfectionism and binge eating and may inform
      etiological models of EDNOS characterized by fasting or purging.

PMID- 16958126
TI  - Hyperthyroidism in anorexia nervosa: case report and review of the literature.
AB  - OBJECTIVE: To report hyperthyroidism as a cause of unexpected weight gain during
      the course of anorexia nervosa (AN). METHOD: A case report and review of the
      literature. RESULTS: A 42-year-old woman with a 27-year history of AN had
      involuntary weight gain when she became hyperthyroid, but lost weight after
      treatment of the hyperthyroidism. An increase in appetite has been reported when
      hyperthyroidism occurs during AN. CONCLUSION: Clinicians should include
      hyperthyroidism in the differential diagnosis of unexpected weight gain in AN.

PMID- 16958127
TI  - Pitx2c overexpression promotes cell proliferation and arrests differentiation in
      myoblasts.
AB  - Pitx2 is a paired-related homeobox gene that has been shown to play a central
      role during development. In the mouse, there are three isoforms, Pitx2a, b, and
      c, which differ only in their amino terminal regions. Pitx2 is expressed in
      myotomes, myoblasts, and myofibers and may be involved in muscle patterning.
      However, the mechanism by which Pitx2 acts in muscle cell lineages as well as the
      distinct functions of the individual isoforms have not been investigated. In this
      study, we used Sol8 myoblasts to investigate the function of Pitx2 in skeletal
      myogenesis. We found that Pitx2c is the main Pitx2 isoform present in Sol8
      myoblasts. Overexpression of Pitx2c in Sol8 myoblasts inhibited myocyte
      differentiation and myotube formation. Furthermore, Sol8 cells overexpressing
      Pitx2c maintained high proliferative capacity and a significant up-regulation of
      the cell cycle genes cyclin D1, cyclin D2, and c-myc. Gene expression analysis
      for Pax3 and the s MyoD and myogenin showed that Pitx2c-overexpression caused
      Sol8 cells to remain as myoblasts, in an undifferentiated myogenic state.
      Furthermore, down-regulation of the muscle-specific genes sTnI and MyHC3
      demonstrated that Sol8-overexpressing Pitx2c myoblasts failed to reach terminal
      differentiation. This study sheds light on previously unknown functions of the
      Pitx2c isoform in balancing proliferation vs. differentiation in a myogenic cell
      line.

PMID- 16958128
TI  - Should night eating syndrome be included in the DSM?
AB  - OBJECTIVE: This article examines the status of the literature on night-eating
      syndrome (NES) according to five criteria that have been proposed by Blashfield,
      Sprock, and Fuller(1) (Compr Psychiatry 1990; 31:15-19) to determine whether NES
      warrants inclusion in the psychiatric nosology as a distinct eating disorder.
      METHOD: Relevant research papers were identified in Medline and PsychInfo using
      the search term "night-eating syndrome." RESULTS: None of the five criteria was
      met. Specifically, at the time of review, there were not yet 25 empirical papers
      on NES; no commonly accepted definition of or assessment approach to NES has been
      adopted; the utility and validity of NES need to be established, and NES needs to
      be differentiated more clearly from other eating disorder syndromes. CONCLUSION:
      This review suggests that the most pressing step toward clarifying the status of
      NES is to develop a uniform definition of NES. Once accomplished, research can
      progress to accumulating the necessary evidence to determine whether NES should
      be included in the fifth edition of the Diagnostic and Statistical Manual of
      Mental Disorders.

PMID- 16958129
TI  - Experimental test of the affect-regulation theory of bulimic symptoms and
      substance use: a randomized trial.
AB  - OBJECTIVE: Conduct a randomized trial to test whether a cognitive behavioral
      intervention designed to decrease depressive symptoms produces subsequent
      decreases in bulimic and substance use symptoms. METHOD: Female participants (N =
      145) with elevated depressive symptoms were randomly assigned to a 4-session
      depression intervention or a measurement-only condition and assessed through 6
      month follow-up. RESULTS: Relative to control participants, intervention
      participants showed decreases in depressive symptoms. Intervention participants
      also showed significantly greater reductions in bulimic symptoms, but not
      substance use, and change in depressive symptoms mediated this effect for bulimic
      symptoms. CONCLUSION: The results provide experimental support for the theory
      that affect disturbances contribute to bulimic pathology, but do not support the
      affect regulation theory of substance use.

PMID- 16958130
TI  - Continuous dopaminergic stimulation: Is it the answer to the motor complications
      of Levodopa?
AB  - Continuous dopaminergic stimulation (CDS) is a treatment strategy hypothesized to
      avoid or reduce the motor complications of long-term levodopa therapy, motor
      fluctuations, and dyskinesia, by preventing or reversing sensitization induced by
      pulsatile dopaminergic stimulation. The CDS hypothesis is itself based on several
      hypotheses. First, tonic dopaminergic stimulation is physiological. Second,
      sensitization is undesirable and should be reversed. Third, reduction of off time
      and dyskinesia can be induced simultaneously. Finally, clinical studies
      substantiate the CDS hypothesis. The evidence for these hypotheses is reviewed,
      and the need for randomized clinical trials that rigorously test the CDS
      hypothesis is emphasized.

PMID- 16958131
TI  - Tetrabenazine therapy of pediatric hyperkinetic movement disorders.
AB  - Tetrabenazine (TBZ), a presynaptic dopamine depletor and postsynaptic dopamine
      receptor blocker, is widely used for the treatment of hyperkinetic movement
      disorders in adults. However, reports of its use in children are limited. We
      review the efficacy and tolerability of TBZ therapy in 31 children with
      hyperkinetic movement disorders refractory to other medications. TBZ was
      effective in reducing the severity of movement disorders resistant to treatment
      with other medicines. When compared to adult patients, pediatric patients
      required higher doses. Side effects were similar to the adult population;
      however, children had a lower incidence of drug-induced Parkinsonism.

PMID- 16958132
TI  - Ethyl pyruvate attenuates kainic acid-induced neuronal cell death in the mouse
      hippocampus.
AB  - Recent studies have shown that ethyl pyruvate (EP) acts as an anti-inflammatory
      molecule in several cell lines including RAW264.7 macrophages. However, the
      potential therapeutic value of EP for the treatment of the pathologic brain has
      not been investigated fully. In the present study, we examined whether EP has a
      beneficial effect on KA-induced neuronal cell death. Intracerebroventricular
      (i.c.v.) injection of 0.94 nmol (0.2 mug) of KA produced typical neuronal cell
      death in the CA1 and CA3 pyramidal layers of the hippocampus, and the systemic
      administration of EP significantly attenuated KA-induced neuronal cell death in
      these regions. Ethyl pyruvate was found to exert a protective effect when it was
      injected as late as 12 hr after KA-injection. Moreover, this EP-induced
      neuroprotection was accompanied by reduced levels of reactive gliosis and COX-2,
      IL-1beta, and TNF-alpha in the hippocampus. In addition, in passive avoidance
      tests, KA-induced memory impairment was improved markedly by EP. These results
      suggest that EP has a therapeutic potential for suppressing KA-induced
      pathogenesis in the brain.

PMID- 16958133
TI  - Body weight in patients with Parkinson's disease.
AB  - There is some evidence suggesting that Parkinson's disease (PD) patients exhibit
      lower body weight when compared to age-matched healthy subjects. Low body mass
      index (BMI) is correlated with low bone mineral density, both of which are major
      risk factors for hip fractures. Possible determinants of weight loss in PD
      patients include hyposmia, impaired hand-mouth coordination, difficulty chewing,
      dysphagia, intestinal hypomotility, depression, decreased reward processing of
      dopaminergic mesolimbic regions, nausea, and anorexia as the side effects of
      medication, and increased energy requirements due to muscular rigidity and
      involuntary movements. It is unclear whether PD patients in general, or only a
      subgroup of those affected, definitely show lower BMI in the advanced stages of
      the disease. We therefore recommend that the body weight of PD patients be
      monitored monthly as the disease progresses, and that a patient's nutrition
      should be supplemented with sufficient amounts of vitamin D and calcium to reduce
      the risk of hip fractures and strengthen bone density. Because meal times may
      coincide with unpredictable off periods associated with akinesia and impaired
      hand-mouth coordination, PD patients also need flexible food schedules that
      accommodate the associated symptoms of this disease.

PMID- 16958134
TI  - Metric attributes of the unified Parkinson's disease rating scale 3.0 battery:
      part II, construct and content validity.
AB  - This article is the second of a two-part series concerning the metric properties
      of the following three Parkinson's disease (PD) scales: modified Hoehn and Yahr
      staging (H&Y), Schwab and England (S&E), and Unified Parkinson's Disease Rating
      Scale (UPDRS) 3.0. Part II focuses on construct and content validity. To assess
      construct validity, a sample of 1,136 PD patients completed the above-mentioned
      PD scales. Correlation coefficients between measures of disability and
      dysfunction [S&E, UPDRS Activities of Daily Living (ADL), and UPDRS Motor
      Examination] were |r| = 0.69-0.77, indicating good convergent validity. Results
      showed that the S&E (F(5,945) = 193.47; P < 0.0001) and UPDRS subscales
      discriminated between modified H&Y stages (F(20,2784) = 25.28; P < 0.001). A
      panel of 12 to 13 international experts rated the relevance of the scales and
      items. This enabled the scales' content validity index to be calculated, which
      ranged from 41.7% (UPDRS Mentation) to 83.3% (UPDRS Motor Examination). In
      conclusion, while the modified H&Y, S&E, and UPDRS displayed satisfactory
      construct validity, the content validity of all scales except UPDRS Motor
      Examination failed to attain adequate standards.

PMID- 16958135
TI  - Hepatitis C virus--biology, host evasion strategies, and promising new therapies
      on the horizon.
AB  - Hepatitis C reduces the quality of life for some 170 million people around the
      globe and is one of the most prevalent diseases on the planet. It is caused by
      the hepatitis C virus (HCV) that is replicated by an error-prone polymerase and
      therefore undergoes rapid evolution. To date, although much has been learned
      about the biology of HCV, only a partially effective combination therapy
      comprised of ribavirin and pegylated-interferon-alpha is available to hepatitis C
      sufferers. Given the prevalence of hepatitis C, together with the fact that
      almost half the chronically infected HCV patients are refractory to current
      therapy, there is an urgent need for an efficacious immunoprophylactic that
      protects individuals from HCV infection, as well as drugs that impede the viral
      life cycle effectively and eradicate infection. Herein, I provide an overview of
      the molecular biology of HCV, highlighting the functions of different virally
      encoded proteins in terms of how they alter signaling pathways of host cell to
      establish an infection and discuss whether a more promising therapy for treating
      hepatitis C is anywhere in sight.

PMID- 16958136
TI  - Inhibitors of CXCR4 affect the migration and fate of CXCR4+ progenitors in the
      developing limb of chick embryos.
AB  - Chemokines and their receptors play major roles in numerous physiological and
      pathological processes during development and disease. CXCR4 is the most
      abundantly expressed chemokine receptor during development. In contrast to other
      chemokine receptors, CXCR4 binds and is activated exclusively by its ligand
      stromal derived factor-1 (SDF-1) or CXCL12. SDF-1 signaling has a wide range of
      effects on CXCR4-expressing cells depending on the cell type ranging from cell
      growth to adhesion, chemotaxis, and migration. CXCR4 also serves as a co-receptor
      for HIV-1 entry into T-cells and has been implicated in the pathogenesis of
      rheumatoid arthritis and cancer growth and invasion. Numerous inhibitors and
      antagonists of CXCR4 have been produced and are being tested for their efficiency
      to target its role in pathogenesis. Our initial expression analysis revealed that
      CXCR4 is expressed by the migrating myogenic and angiogenic precursors in the
      developing chick limb. In this study, we used the most specific peptidic
      inhibitors of CXCR4, T140 and its analog TN14003, to analyse the effect of
      blocking CXCR4/SDF-1 signaling on the undetermined bioptent migratory progenitors
      in the developing chick limb. Our results point to defects in migration and an
      altered differentiation program of these CXCR4-expressing progenitor pool in the
      limb.

PMID- 16958137
TI  - Effect of pH on biological phosphorus uptake.
AB  - An anaerobic aerobic laboratory scale sequencing batch reactor (SBR) was operated
      to study the effect of pH on enhanced biological phosphorus removal. Seven steady
      states were achieved under different operating conditions. In all of them, a
      slight variation in the pH value was observed during anaerobic phase. However, pH
      rose significantly during aerobic phase. The increase observed was due to
      phosphorus uptake and carbon dioxide stripping. When pH was higher than 8.2-8.25
      the phosphorus uptake rate clearly decreased. The capability of Activated Sludge
      Model No. 2d (ASM2d) and Biological Nutrient Removal Model No. 1 (BNRM1) to
      simulate experimental results was evaluated. Both models successfully
      characterized the enhanced biological phosphorus removal performance of the SBR.
      Furthermore, BNRM1 also reproduced the pH variations observed and the decrease in
      the phosphorus uptake rate. This model includes a switch function in the kinetic
      expressions to represent the pH inhibition in biological processes. The pH
      inhibition constants related to polyphosphate storage process were obtained by
      adjusting model predictions to measured phosphorus concentrations. On the other
      hand, pH inhibition should be included in ASM2d to accurately simulate
      experimental phosphorus evolution observed in an A/O SBR.

PMID- 16958138
TI  - Nitrilotriacetic acid degradation under microbial fuel cell environment.
AB  - The removal of nitrilotriacetic acid (NTA) was studied under anaerobic conditions
      using oligotrophic and copiotrophic microbial fuel cells (MFCs) as a novel
      wastewater treatment process. Over 85% of NTA was removed from oligotrophic MFCs
      enriched and maintained with fuel containing NTA, whilst the value was around 20%
      in oligotrophic MFCs fed with NTA-free fuel, and in copiotrophic MFCs enriched
      with NTA containing fuel. The oligotrophic MFCs generated current with
      concomitant utilization of NTA when served as the sole organic compound,
      suggesting that NTA is oxidized its suitability as fuel in the MFCs.

PMID- 16958139
TI  - A new approach to the remediation of heavy metal liquid wastes via off-gases
      produced by Klebsiella pneumoniae M426.
AB  - When the off-gas from an aerobic culture of Klebsiella pneumoniae M426 grown in
      the absence of added heavy metals was passed through a solution of Hg(2+),
      Cd(2+), Pb(2+), or Cu(2+) a yellow-white (Hg), white (Cd, Pb), or blue (Cu)
      precipitate was formed. Metal removal from solution was >97% within 2 h at
      initial concentrations of (as metal): Hg, 8.5; Cd, 12.6; Pb, 7.8; Cu, 9.5 mg/mL.
      Mercury was removed from solution at pH 2 and in up to 1 M NaCl. Energy
      dispersive X-ray microanalysis (EDX) of the precipitates showed them to comprise
      metal, sulfur and carbon in the case of Hg, Cd, and Pb, and, in the case of Cd
      and Pb, also oxygen. The pH of the solution increased by 1-2 units at an initial
      pH of 7 and by 4-5 units at an initial pH of 2. In the case of cadmium and lead,
      the presence of crystalline metal carbonates and hydroxides was confirmed by X
      ray powder diffraction (XRD) analysis and additional peaks were seen which could
      not be assigned to known compounds in the diffraction file database. In the case
      of copper, hydroxides, and a form of copper sulfate, were found. In the case of
      mercury the XRD patterns could not be assigned to any known compound, except for
      HgCl in the solution at the acidic initial pH. The absence of sharp peaks in the
      pattern for the Hg-precipitate was indicative of poorly crystalline,
      nanocrystalline or amorphous material. The unknown mercury compound, since it
      contained non-carbonate carbon, was suggested to be derived from a volatile
      organothiol in the gases evolved from the culture. Analysis of the culture head
      gas by GC-MS showed the presence of dimethyldisulfide as a likely precipitant. No
      sulfur compound was found using XRD analysis in the case of cadmium and lead,
      although EDX analysis suggested this as a major component and the lack of XRD
      pattern is evidence for a non-crystalline metal-organothiol. The exact chemistry
      of the new materials remains to be elucidated but metal precipitation via a
      biogenic organothiol is a potentially effective approach to the remediation of
      aggressive metal wastes.

PMID- 16958140
TI  - Comparative testing of tangential microfiltration for microbial cultures.
AB  - In an attempt to extend and intensify the productive periods of bioprocesses, a
      self-cleaning tangential filtration device was examined. Built into a special
      design bioreactor, its cell retention was evaluated for continuous-flow operation
      with selected examples of bacteria (Escherichia coli), yeasts (Sacharomyces
      cerevisiae), and filamentous fungi (Aspergillus niger). Performance
      characteristics such as filtration rates and cell accumulation were assessed as a
      function of filter rotational speed, operating pressure, cultivation time, and
      microfilter type (i.e., membrane or porous metallic). The highest flux of cell
      free filtrate for each culture type was achieved using a 0.45-micron membrane
      covered microfilter. While the respective yeast (S. cerevisiae) and bacterial (E.
      coli) cell concentrations were enhanced by as much as 16- and 8-fold over the
      batch growth levels, the representative A. niger fungal cultivation was less
      satisfactory because of progressively declining filtration rates limited by
      hydraulically resistant layers of microbial surface growth quite resistant to in
      situ filter backflushing with gas. Maximum steady-state flux was independent of
      operating pressure, yet was enhanced at rotational speeds up to about 800 rpm.
      Higher speeds offered no further improvements. The overall fermentation process
      was limited by the moderate levels of attainable flux which restricted the feed
      and dilution rates. The maximum attainable stabilized fluxes were 26-40 L/m(2) x
      h.

PMID- 16958141
TI  - Controlling light-use by Rhodobacter capsulatus continuous cultures in a flat
      panel photobioreactor.
AB  - The main bottleneck in scale-up of phototrophic fermentation is the low
      efficiency of light energy conversion to the desired product, which is caused by
      an excessive dissipation of light energy to heat. The photoheterotrophic
      formation of hydrogen from acetate and light energy by the microorganism
      Rhodobacter capsulatus NCIMB 11773 was chosen as a case study in this work. A
      light energy balance was set up, in which the total bacterial light energy
      absorption is split up and attributed to its destinations. These are biomass
      growth and maintenance, generation of hydrogen and photosynthetic heat
      dissipation. The constants defined in the light energy balance were determined
      experimentally using a flat-panel photobioreactor with a 3-cm optical path. An
      experimental method called D-stat was applied. Continuous cultures were kept in a
      so-called pseudo steady state, while the dilution rate was reduced slowly and
      smoothly. The biomass yield and maintenance coefficients of Rhodobacter
      capsulatus biomass on light energy were determined at 12.4 W/m(2) (400-950 nm)
      and amounted to 2.58 x 10(-8) +/- 0.04 x 10(-8) kg/J and 102 +/- 3.5 W/kg,
      respectively. The fraction of the absorbed light energy that was dissipated to
      heat at 473 W/m(2) depended on the biomass concentration in the reactor and
      varied between 0.80 and 0.88, as the biomass concentration was increased from 2.0
      to 8.0 kg/m(3). The process conditions were estimated at which a 3.7% conversion
      efficiency of absorbed light energy to produced hydrogen energy should be
      attainable at 473 W/m(2).

PMID- 16958142
TI  - A study to determine the incidence of structural congenital heart disease in
      monochorionic twins.
AB  - OBJECTIVE: To determine the incidence of structural heart disease in at least one
      of a monochorionic (MC) twin pair excluding any cardiac effects of twin-twin
      transfusion syndrome (TTTS). METHOD: A cohort study of 165 sets of MC twins
      undergoing detailed fetal echocardiography in a tertiary unit over a 4-year
      period. RESULTS: The overall risk of at least one of a MC twin pair having a
      structural congenital cardiac anomaly was 9.1% (15/165); for monochorionic
      diamniotic (MC/DA) twins, this figure was 7.0% (11/158) but for monochorionic
      monoamniotic (MC/MA) twins the risk for at least one affected twin was 57.1%
      (4/7). If one of a pair of MC twins was affected, the risk to the other twin for
      a structural cardiac anomaly was 26.7% (4/15). CONCLUSIONS: The incidence of
      structural heart disease in MC twins is increased, independent of TTTS. This
      justifies referral of these pregnancies for detailed fetal echocardiography as
      part of their assessment. If one twin is affected, the risk to the other twin is
      increased further.

PMID- 16958143
TI  - Paternal gonadal mosaicism of NIPBL mutation in a father of siblings with
      Cornelia de Lange syndrome.
AB  - OBJECTIVES: We report two siblings, a boy and a girl, with Cornelia de Lange
      syndrome (CdLS), born to unaffected parents, and attempt to delineate the
      underlying molecular mechanism leading to familial recurrence. METHODS: Nipped-B
      like (NIPBL) gene mutations were screened using in denaturing high-performance
      liquid chromatography and sequencing in peripheral blood samples, from one of the
      affected siblings and her parents, as well as from a sperm sample from the
      father. RESULTS: A heterozygous missense NIPBL mutation, D2433G, was identified
      in the peripheral blood sample of the affected girl, but not in the peripheral
      blood samples of her parents. The D2433G mutation was also found in the sperm
      sample of the father. CONCLUSION: Gonadal mosaicism represents an
      underappreciated feature of the inheritance pattern of CdLS. To our knowledge,
      the girl represents the first CdLS patient whose father was documented to have a
      population of mutant sperm. When a sperm analysis indicates the presence of a
      mutant allele, it may be reasonable to offer prenatal genetic testing to the
      family in subsequent pregnancies, given that the sensitivity of fetal
      ultrasonography is relatively low.

PMID- 16958144
TI  - Prenatal diagnosis of congenital malformations and parental psychological
      distress--a prospective longitudinal cohort study.
AB  - OBJECTIVE: To test whether postnatal psychological distress in parents of babies
      with congenital malformations is reduced by prenatal diagnosis. METHODS: A
      prospective observational longitudinal cohort study was conducted at two
      Norwegian hospitals. We included 293 parents of babies with congenital
      malformations (prenatal detection rate: 36.5%) referred for neonatal surgery and
      249 parents of healthy babies (comparison group). Parental psychological
      responses were assessed on three postnatal occasions by psychometric instruments
      (GHQ-28, STAI-X1, and IES). RESULTS: Significantly increased psychological
      distress (GHQ-28) was reported by parents who received prenatal diagnosis as
      compared to postnatal diagnosis; acutely 28.9 versus 24.4, P = 0.006 (comparison
      group: 19.6); at 6 weeks 26.8 versus 21.5, P < 0.001 (comparison group: 17.7);
      and at 6 months 22.6 versus 18.7, P = 0.015 (comparison group: 16.6). Mothers
      consistently reported higher levels of distress than fathers. Multiple linear
      regression analysis showed that prenatal diagnosis and being a mother
      significantly predicted severity of acute psychological distress. At 6 weeks and
      6 months, mortality and associated anomalies were significant independent
      predictors of psychological distress. CONCLUSION: Controlling for other
      covariates, we found that prenatal diagnosis of congenital malformations was a
      significant independent predictor of acute parental psychological distress after
      birth.

PMID- 16958145
TI  - Prenatally detected double trisomy: Klinefelter and Down syndrome.
AB  - Double trisomies are a rare occurrence. We report the first case of a Down and
      Klinefelter's syndrome (48,XXY,+21) in a fetus that was prenatally diagnosed
      during the 15th week of pregnancy. Even though the nasal bone was present, and
      the color-Doppler study of the ductus venosus and the nuchal thickness were
      normal, the maternal serum test results indicated an increased risk of Down
      syndrome and consequentially a genetic amniocentesis was performed. A 48,XXY,+21
      karyotype was observed and the patient decided to terminate the pregnancy. In
      this case, we did not find the typical ultrasound (US) signs that would have led
      us to the chromosomopathy; furthermore, we emphasize the advantages of using
      biochemical screening which, in our case, were crucial in arriving at the correct
      diagnosis.

PMID- 16958146
TI  - Single large study or meta-analysis parameters: choosing the most appropriate
      tool for Down syndrome screening in the first trimester.
AB  - AIM: The aim of the present study is to determine whether the use of population
      parameters derived from meta-analysis produces better test characteristics in the
      first-trimester combined screening than those obtained from large single studies,
      when screening for Down syndrome (DS) in singleton pregnancies. METHODS:
      Retrospective analysis was done on a database of 4248 singleton pregnancies,
      including 13 cases of DS, for which the values of three markers used in the
      combined first-trimester test were available. The risk of DS was calculated for
      each mother from the different population parameters derived by meta-analysis or
      from two large single studies: the Fetal Medicine Foundation study (FMF) and the
      Serum, Urine and Ultrasound Screening Study (SURUSS). RESULTS: When the detection
      rate was fixed at about 85%, the false-positive rate was significantly higher
      (Chi-square = 53.49, p < 0.0001) when the parameters obtained by the meta
      analysis (6.25%) were compared with the two single studies (FMF, 4.15% and
      SURUSS, 3.75%). CONCLUSIONS: This study highlights the importance of selecting
      appropriate population parameters when insufficient DS cases are available in the
      study population. When screening for DS in singleton pregnancies during the first
      trimester, the use of population parameters derived from single large studies
      produced better test characteristics.

PMID- 16958147
TI  - Multicenter Phase II study of CyclOBEAP regimen for elderly patients with poor
      prognosis aggressive lymphoma.
AB  - We treated elderly patients (65-69 years) who had aggressive lymphoma with the
      CyclOBEAP regimen, and we studied the safety and efficacy of this treatment. The
      CyclOBEAP regimen was administered over a total period of 12 weeks. Doxorubicin
      40 mg/m(2) was given every 2 weeks in combination with either cyclophosphamide
      800 mg/m(2) or etoposide 70 mg/m(2) qd x 3. During the alternate weeks, non
      myelosuppressive vincristine 1.0 mg/m(2) was given either with bleomycin 10
      mg/m(2) or alone. Prednisolone 40 mg/m(2) was administered daily for three 14-day
      periods during weeks 1-2, 5-6 and 9-10. There were 51 eligible patients. A
      complete response was achieved in 42 patients (82%). The 5-year overall survival
      (OS) rate was 60.6% and progression-free survival (PFS) rate was 51.8%. WHO grade
      4 neutropenia was observed in 32 patients and thrombocytopenia in 8 patients. We
      showed that the CyclOBEAP regimen can be safely used in the treatment of
      aggressive lymphoma in elderly patients and it achieved a high rate of remission.

PMID- 16958148
TI  - Trends in consumption of psychiatric drugs in Serbia and Montenegro 2000-2004.
AB  - PURPOSE: To investigate the trends in psychiatric drugs utilization in Serbia and
      Montenegro over the 5-years period (2000-2004). MATERIALS AND METHODS: The
      wholesale data issued by the manufacturers or distributors were used. Also, the
      lists of drugs used from the Institute of Mental Health (institution which
      provides primary, secondary and tertiary psychiatric care) were used to
      corroborate the wholesale data. The utilization of drugs in general population
      was calculated using ATC/DDD methodology, and was expressed in Defined Daily
      Doses (DDD) per 1000 inhabitants per day. The utilization of drugs in the
      Institute of Mental Health was calculated from the hospital pharmacy records and
      was expressed as the number of DDDs per 100 bed-days. The statistics was
      performed using standard statistical methods. RESULTS: The general consumption of
      psychiatric drugs in Serbia and Montenegro significantly increased during the
      2000-2004 period (from 45.1 DDD/1000 inhabitants/day in 2000 to 69.1 DDD/1000
      inhour/day in 2004). The general utilization of anxiolytic/hypnotic drugs surged
      significantly, but the inhospital use remained rather stable. The most prominent
      changes were noted in the utilization of antidepressants, which doubled in that
      period, both in general and inhospital settings. Among antipsychotics in general
      population, there is a significant increase in the utilization of clozapine. In
      inhospital setting, there is a significant increase of total utilization of
      antipsychotic drugs, but this is also mainly on the account of atypicals.
      CONCLUSIONS: The total consumption of psychiatric drugs significantly increased.
      The utilization of anxiolytic/hypnotic drugs in 2004 reached 60 DDDs/1000
      inhabitants/day, which is in collision with the trend in developed countries. It
      is necessary to form national guidelines for prescribing anxiolytic/hypnotic
      drugs, in order to rationalize their use. More favourable is the antidepressant
      (SSRIs in particular) and atypical antipsychotic drugs utilization increase.

PMID- 16958149
TI  - Automated detection of infectious disease outbreaks: hierarchical time series
      models.
AB  - The purpose of infectious disease surveillance is to inform the public health
      policy makers on the incidence and trends of infectious diseases and to trigger
      appropriate actions to control infectious disease outbreaks. The enormous amount
      of data collected with automated laboratory-based surveillance systems require
      automated algorithms for detecting unexpected aberrations that may signal
      infectious disease outbreaks. In this paper, we explore the potential of
      hierarchical time series models to detect deviations from expected incidence. As
      these count data are extremely noisy it can be expected that these models are
      suitable to detect signal from noise and accommodate for possible
      autocorrelation. The proposed procedure consists of three steps; (1) the model
      parameters are estimated by empirical Bayes on a training period of, e.g. a year;
      (2) the expected values are updated for small time steps (e.g. daily) as new data
      arrive; (3) threshold levels are updated conditionally on the past expected
      values and an alarm is triggered when the threshold level is exceeded. To test
      the potential of the models we estimated sensitivity, specificity and timeliness
      on simulated time series and compared the results with an alternative approach of
      a linear regression model adjusted for trends and season. We also used two
      observed series for Rubella notifications and Salmonella infections and compared
      our findings with the expert opinions on these series. The hierarchical time
      series models approach shows high sensitivity and specificity and correctly
      identifies outbreaks at an early stage. This, in our opinion, makes the proposed
      model a reliable tool for adequate automated detection of infectious disease
      outbreaks.

PMID- 16958150
TI  - Twin reversed arterial perfusion: fetoscopic laser coagulation of placental
      anastomoses or the umbilical cord.
AB  - OBJECTIVE: To assess the feasibility and outcome of fetoscopic laser coagulation
      in pregnancies with twin reversed arterial perfusion (TRAP) sequence. METHODS: In
      a prospective multicenter study, percutaneous fetoscopic laser coagulation of
      placental anastomoses (n = 18) or the umbilical cord of the acardiac twin (n =
      42) was performed in 60 consecutive pregnancies at a median gestational age of
      18.3 (range, 14.3-24.7) weeks under local or locoregional anesthesia. RESULTS:
      Vascular coagulation with arrest of blood flow was achieved in 82% (49/60) of
      cases by laser alone and in a further 15% (9/60) by laser coagulation in
      combination with bipolar forceps. The overall survival rate of the pump twin was
      80% (48/60). Median gestational age at delivery was 37.4 (range, 23.7-41.4) weeks
      and the median interval between the procedure and delivery was 18.2 (range, 1.1
      25.7) weeks. Median birth weight was 2720 (range, 540-3840) g. Preterm premature
      rupture of membranes before 34 weeks' gestation occurred in 18% (11/60) at a
      median of 62 (range, 1-102) days after the procedure. However, only two (3%)
      women delivered within 28 days of the procedure. CONCLUSIONS: Fetoscopic laser
      coagulation of placental vascular anastomoses or the umbilical cord of the
      acardiac twin is an effective treatment of TRAP sequence, with a survival rate of
      80%, and 67% of pregnancies with surviving pump twins going beyond 36 weeks'
      gestation without further complications.

PMID- 16958152
TI  - Three-dimensional sagittal reconstruction of the corpus callosum: fact or
      artifact?

PMID- 16958151
TI  - Spontaneous rupture of sacrococcygeal teratoma associated with acute fetal
      anemia.
AB  - Sacrococcygeal teratoma (SCT) is the most common congenital tumor, with affected
      fetuses having a high risk of perinatal complications and death. We report a case
      of a fetus with an SCT that developed acute anemia due to spontaneous rupture of
      the tumor in utero. The fetus was referred at 25 weeks' gestation for evaluation
      of a large solid and cystic mass in the sacral region. There were no signs of
      hydrops or placentomegaly. At 33 weeks' gestation, loss of variability in the
      fetal heart rate pattern was recorded. Doppler ultrasonography showed increased
      middle cerebral artery peak systolic velocity, suggesting fetal anemia. Markedly
      bloody amniotic fluid, with 82% hemoglobin F, was observed on amniocentesis,
      suggesting rupture of the SCT with active fetal bleeding. An emergency Cesarean
      section was performed. At delivery, the tumor was bleeding actively and the
      neonatal hemoglobin concentration was 3.1 g/dL. There were no findings of
      hemorrhage or necrosis within the tumor. The neonate received a blood
      transfusion, and surgical resection of the tumor was carried out on the first day
      after delivery. Postoperatively, the baby did well. We suggest that fetal SCTs
      run the risk of inducing acute fetal anemia due to intrauterine hemorrhage of the
      tumor, a finding which could lead to an earlier and more appropriate management
      of this condition.

PMID- 16958153
TI  - Incorporating prior information via shrinkage: a combined analysis of genome-wide
      location data and gene expression data.
AB  - Transcriptional control is a critical step in regulation of gene expression.
      Understanding such a control on a genomic level involves deciphering the
      mechanisms and structures of regulatory programmes and networks. A difficulty
      arises due to the weak signal and high noise in various sources of data while
      most current approaches are limited to analysis of a single source of data. A
      natural alternative is to improve statistical efficiency and power by a combined
      analysis of multiple sources of data. Here we propose a shrinkage method to
      combine genome-wide location data and gene expression data to detect the binding
      sites or target genes of a transcription factor. Specifically, a prior 'non
      target' gene list is generated by analysing the expression data, and then this
      information is incorporated into the subsequent binding data analysis via a
      shrinkage method. There is a Bayesian justification for this shrinkage method.
      Both simulated and real data were used to evaluate the proposed method and
      compare it with analysing binding data alone. In simulation studies, the proposed
      method gives higher sensitivity and lower false discovery rate (FDR) in detecting
      the target genes. In real data example, the proposed method can reduce the
      estimated FDR and increase the power to detect the previously known target genes
      of a broad transcription regulator, leucine responsive regulatory protein (Lrp)
      in Escherichia coli. This method can also be used to incorporate other
      information, such as gene ontology (GO), to microarray data analysis to detect
      differentially expressed genes.

PMID- 16958154
TI  - Monochorionic pseudomonoamniotic twin pregnancy with fetal demise of one twin and
      development of maternal consumptive coagulopathy.

PMID- 16958156
TI  - Distinction of tris(diimine)ruthenium(II) enantiomers chiral by virtue of helical
      chirality: temperature-dependent deuterium NMR spectroscopy in partially oriented
      phases.
AB  - 2H NMR spectra of perdeuterated tris(diimine)ruthenium(II) complexes have been
      recorded in lyotropic liquid crystalline phase formed by the chiral polypeptide,
      poly-gamma-benzyl-L-glutamate (PBLG) and co-solvents. It is demonstrated that the
      left- and right-rotation isomers of these octahedral metal complexes with D3
      symmetry can be distinguished. The effects of temperature and ligand size on
      spectral resolution were also studied. Although in the case of free bipyridine
      ligands excellent optical resolution could be obtained at room temperature in the
      complexes studied, the increase in ligand size has a detrimental effect on the
      resolution. This can be compensated to some extent by elevating the sample
      temperature and decreasing the deuterium relaxation rates, but the available
      temperature range and therefore the applicability of the technique are limited.

PMID- 16958155
TI  - Therapeutic profile of orphan medicines.
AB  - PURPOSE: To characterise the therapeutic profile of orphan medicines. MATERIALS
      AND METHODS: A cross-sectional study was performed during 2 months in a
      convenience sample of seven hospital pharmacy services, in the region of Lisbon.
      Data were collected, from pharmaceutical service's records. RESULTS: A total of
      18 orphan medicines, were dispensed to 355 patients with rare diseases. Most
      patients were adults (76.4%). Premature and neonates accounted with 50.0% of the
      paediatric patients. Differences were not found between the proportion of male
      and female patients across age groups (p = 0.762). Only 18.3% were inpatients. A
      high proportion of paediatric inpatients (58.3%) were seen in relation to adult
      inpatients (5.9%) (p = 0.001). In general, anti-neoplastic and immunomodulating
      agents for rare cancers were the most frequent dispensed medicines (51.3%). In
      relation to paediatrics, Caffeine Citrate for primary apnoea of premature
      newborns had the higher frequency distribution (57.1%). Five (71.4%) medicines
      dispensed for paediatrics, do not have market authorisation and the remaining
      (28.6%) were used off-label. For pulmonary arterial hypertension 19 of 27
      patients (70.3%) were treated with Bosentan. According to evidence-based clinical
      practice guidelines, Bosentan has a good level of evidence and substantial
      benefit: grade of recommendation A. CONCLUSIONS: Most orphan medicines dispensed
      to paediatrics and adults were not licensed.A special pharmacovigilance program
      and a risk management plan through the entire life cycle should be implemented,
      towards effectiveness and safety of orphan medicines.

PMID- 16958157
TI  - 29Si spin-lattice NMR relaxation in microporous silica-based materials with high
      Mn2+ concentrations.
AB  - The 29Si T1 time measurements have been performed under magic angle spinning for
      supermicroporous Si/Mn materials 1-6 containing Mn2+ in concentrations of 0 (1),
      1.2 (2), 2.5 (3), 3.8 (4), 15 (5) and 19.8 wt% (6). It has been found that the
      central lines, corresponding to isotropic chemical shifts, and their sidebands
      relax differently in samples 2-4 with relatively small Mn2+ contents. Because the
      relaxation curves for 1-6 are nonexponential and identical for 6 at spinning
      rates of 5, 10 and 12 kHz, dipolar relaxation via the paramagnetic centers is
      dominant. The relaxation data have been interpreted as a function of Mn2+
      concentrations in terms of incorporation of the Mn2+ ions into the silica lattice
      when their concentration is small (<or=2.5 wt%). At higher concentrations, most
      of the manganese is located on the surface of the silica.

PMID- 16958158
TI  - Peace has come to southern Sudan, but challenges remain.

PMID- 16958159
TI  - The UK's public health paradox.

PMID- 16958160
TI  - Ernst Mayr (1904-2005): evolutionary leader, protagonist, and visionary.

PMID- 16958161
TI  - [How could it be so wrong? Swedish hand surgeons are locked out from work in
      Europe].

PMID- 16958162
TI  - The application of EMTALA to specialty hospitals--a review of current issues.

PMID- 16958163
TI  - Strengthening health care systems in sub-Saharan Africa.

PMID- 16958164
TI  - Family meals and old age.

PMID- 16958165
TI  - Japan's other research hub.

PMID- 16958166
TI  - Are you aware of glutaraldehyde?

PMID- 16958167
TI  - Modernising medical careers.

PMID- 16958168
TI  - Standardised early warning scoring system.

PMID- 16958169
TI  - Proceedings of the OIE/FAO International Scientific Conference on Avian
      Influenza. April 7-8, 2005. Paris, France.

PMID- 16958170
TI  - Bibliography. Current world literature. Cancer in AIDS.

PMID- 16958171
TI  - Bibliography. Current world literature. Gynecologic Cancer.

PMID- 16958172
TI  - Preventing adverse events caused by emergency electrical power system failures.

PMID- 16958173
TI  - [Patient information. Chronic pancreatitis].

PMID- 16958174
TI  - [Patient information. Fecal and anal incontinence].

PMID- 16958175
TI  - Global trends and paradigm shifts in clinical orthodontics.

PMID- 16958176
TI  - The Herbst appliance: a paradigm change in Class II treatment.

PMID- 16958177
TI  - Transverse dimension and treatment of Class II malocclusion.

PMID- 16958178
TI  - Adult orthodontics in the 21st century: guidelines for achieving successful
      results.

PMID- 16958179
TI  - Orthodontic reduction of lower facial height in open bite patients with skeletal
      anchorage system: beyond traditional orthodontics.

PMID- 16958180
TI  - Before we continue: une pause.

PMID- 16958181
TI  - Heroin addiction: anticipating the reward of heroin or the agony of withdrawal?

PMID- 16958182
TI  - It is time to move: role of lateral diffusion in AMPA receptor trafficking.

PMID- 16958183
TI  - The replacement of graft endothelium by recipient-type cells conditions allograft
      rejection mediated by indirect pathway CD4+ T cells.
AB  - BACKGROUND: Whereas the participation of alloreactive T cells sensitized by
      indirect allorecognition in graft rejection is well documented, the nature of
      recipient antigen presenting cells recognized by indirect pathway CD4+ T cells
      within the graft has yet to be identified. The purpose of this study was to
      determine the role played by graft endothelium replacement in the immune
      recognition of cardiac allografts rejected by indirect pathway CD4+ T cells.
      METHODS: Transgenic RAG2-/- mice expressing I-Ab-restricted male antigen H-Y
      specific TcR were studied for their capacity to reject H-2k male cardiac
      allografts. Chronic vascular rejection in this model was due to the indirect
      recognition of H-Y antigen shed from H-2k male allograft and presented by the
      recipient's own I-Ab APC to transgenic T cells. RESULTS: Immunohistochemical
      analysis of rejected grafts revealed the presence of numerous microvascular
      endothelial cells (EC) that expressed recipient's I-Ab MHC class II molecules.
      This observation suggested that graft endothelium replacement by I-Ab-positive
      cells of recipient origin could stimulate the rejection of male H-2k graft by I
      Ab-restricted H-Y-specific T cells. To investigate further this possibility,
      hearts from H-2b-into-H-2k irradiation bone marrow (BM) chimera were transplanted
      in transgenic recipients. A direct correlation was observed between the presence
      of I-Ab-positive EC within myocardial microvessels and the induction of acute
      rejection of chimeric H-2k male cardiac allografts transplanted in transgenic
      recipients. CONCLUSIONS: We conclude that graft endothelium replacement by
      recipient-type cells is required for the rejection of cardiac allograft mediated
      by indirect pathway alloreactive CD4+ T cells.

PMID- 16958184
TI  - Randomize, then consent: a strategy for improving patient acceptance of
      participation in randomized controlled trials.
AB  - When arthroscopic surgeons are attempting to resolve questions of a therapeutic
      or clinical nature, randomized controlled trials (Level I evidence) are most
      helpful. However, patients may be reluctant or unwilling to participate in
      randomized controlled trials. To improve the feasibility of conducting a
      randomized controlled trial, a strategy for improving patients' willingness to
      participate is proposed. The strategy is simple: randomize, then consent. This
      strategy allows for an informed consent process more specifically focused on the
      specific treatment to which the patient has been assigned. This may be less
      confusing, daunting, and frightening to patients, who thus may be more willing to
      participate in the randomized controlled trial. A disadvantage of randomization
      before consent is that randomization, temporally, is more distant from the actual
      treatment or intervention. However, randomization before consent may represent a
      compromise promoting both better quality consent and increased patient
      willingness to participate in randomized controlled trials.

PMID- 16958185
TI  - Measured and estimated glomerular filtration rate.

PMID- 16958186
TI  - Measured and estimated glomerular filtration rate.

PMID- 16958187
TI  - Part D decisions: like other employers, many states are collecting a new federal
      subsidy for maintaining retiree drug coverage--but for many, that's not their
      "final answer".

PMID- 16958188
TI  - BpTRU(tm) blood pressure monitor for use in a physician's office.
AB  - The BpTRU(tm) is an automated device that takes serial blood pressure (BP)
      measurements in a physician's office. (1) Preliminary data from non-randomized,
      uncontrolled trials suggest that the average of five BpTRU measurements, taken
      while the patient is alone, more reliably reflects "resting" BP compared to
      manual measurements taken with a stethoscope and sphygmomanometer. (2) BpTRU
      helps reduce the overestimation of BP due to improper measurement technique, or
      due to a patient's anxiety in a physician's presence ("white coat" effect). (3)
      The BpTRU device can improve hypertension management by replacing conventional
      manual BP measurements, which are often poorly performed and inaccurate. (4)
      BpTRU is more expensive than the manual manometers used in a physician's office.
      The serial measurement, taken in a private examining room, requires an average of
      six to 12 minutes, which could increase the duration of a patient's visit.

PMID- 16958189
TI  - Febuxostat for prevention of gout attacks.
AB  - (1) Febuxostat is a selective inhibitor of xanthine oxidase. Its use in the
      management of hyperuricemia and gout is being studied. (2) In a 52-week, phase
      III randomized clinical trial, febuxostat was superior to allopurinol for
      lowering uric acid levels. Its efficacy in preventing gout attacks was similar to
      that of allopurinol. Despite a similar rate of adverse effects, individuals on
      febuxostat were more likely to stop treatment than those on allopurinol. (3) The
      most commonly observed adverse effects with febuxostat include liver function
      test abnormalities, diarrhea, headache, nausea, vomiting, abdominal pain, and
      dizziness. (4) Given that renal dysfunction is a risk factor for hyperuricemia
      and gout, the safety and efficacy of febuxostat in this population should be
      considered, but only limited data are available. (5) The diffusion of febuxostat
      may be limited by its price relative to that of allopurinol, regardless of
      whether febuxostat proves to have advantages in specific populations.

PMID- 16958190
TI  - Living near heavy traffic increases asthma severity.

PMID- 16958191
TI  - [Education].

PMID- 16958192
TI  - [Psychiatric past history and health care after compulsory admission. Care use as
      an indicator of the quality of care for patients in compulsory care in
      Rotterdam].
AB  - BACKGROUND: In evaluations of the Act on Special Admissions to Psychiatric
      Hospitals in The Netherlands (Dutch acronym BOPZ) hardly any attention has been
      given to the use of mental health care services before and after a compulsory
      admission. AIM: To investigate whether patterns of care before and after
      compulsory admissions can be considered as indicators of the quality of care
      provided by the mental health services. METHOD: For 623 patients with first-time
      acute compulsory admissions in Rotterdam, the use of the care services was
      monitored over a period of 12 months before and after admission. The outcomes
      were compared for 3 different patient groups: 'old acquaintances', 'newcomers'
      and 'passers-by'. In order to identify differences before an after the
      introduction of the BOPZ Act of 1994, we compared the use made of care facilities
      by patients admitted between 1992 and 1993 and between 1996 and 1997. RESULTS:
      More than one third of the patients admitted to acute compulsory care leaves the
      psychiatric hospital within three weeks. The average length of stay is more than
      two months and in more than half of the cases the first contact with mental
      health services occurs within one week after discharge. Within one year after the
      compulsory admission more than one third of patients is re-admitted and after one
      year more than fifty percent of patients are still receiving mental health care.
      Intensive care is targeted particularly at the patient group referred to as 'old
      acquaintances'. Following the introduction of the BOPZ Act the percentage of
      suicide-threats and cases of self-neglect increased. The number ofcompulsory re
      admissions increased as well. CONCLUSION: The research results provide an
      encouraging picture of the quality of care provided before and after compulsory
      admissions. However, the cases which fail to receive mental health care before
      emergency compulsory admission and miss out on outpatient follow-up emphasise the
      needfor alternative measures such as an earlier conditional compulsory admission
      (voorwaardelijke machtiging) and more intensive outpatient treatment.

PMID- 16958193
TI  - [Psychomotor retardation in depression assessed by visuomotor tasks. Overview and
      achievements of ten years' research].
AB  - BACKGROUND: A new line of research into psychomotor retardation in patients with
      a major depressive disorder began about ten years ago. The purpose of the
      research was twofold: to obtain a clearer understanding of psychomotor
      retardation in patients with a major depressive disorder and to assess the
      importance of psychomotor retardation for the diagnosis and treatment. AIM: To
      present an overview of the results of these studies in which psychomotor
      retardation of these patients was investigated. METHOD: The patients had to
      perform visuomotor tasks involving pen movements. The psychomotor retardation was
      measured by recording their pen movements objectively and accurately by means of
      a computer and digitiser. RESULTS: Patients with major depressive disorder showed
      pronounced psychomotor retardation in the visuomotor tasks. The psychomotor
      retardation appeared to be of both a cognitive and motor nature. The treatment
      study which examined the effect of fluoxetine on psychomotor retardation revealed
      that the cognitive retardation disappeared but the motor retardation remained. It
      was particularly the more retarded patient who responded well to fluoxetine. The
      research that compared the psychomotor retardation in various subtypes of
      depression revealed that patients with major depressive disorder showed
      pronounced retardation but dysthymic patients did not show any retardation.
      Psychomotor retardation was more severe in patients with major depressive
      disorder with melancholic features. CONCLUSION: Psychomotor retardation can play
      an important role in the diagnosis and treatment of depressive disorders.

PMID- 16958194
TI  - [Melatonin. Neurobiological background and neuropsychiatric application in
      children].
AB  - BACKGROUND: The therapeutic use of melatonin in children is based on research
      into the properties of the product and on experience gained from its use in
      specific populations. Our knowledge about melatonin is increasing steadily. AIM:
      To summarise the state of our knowledge regarding melatonin and to assess the
      clinical relevance of this knowledge. METHOD: The PsycINFO and Pub Med databases
      were used to locate and study the relevant literature, using as key words
      'melatonin', 'child*' and 'adolescen*'. RESULTS: Melatonin is a fat-soluble neuro
      hormone which is produced in the pineal gland and is characterised by a circadian
      secretion that operates via a feedback circuit. Research has identified various
      neurobiological mechanisms which have chronobiotic, hypnotic, anticonvulsive,
      anxiolytic and antioxidant effects. With regard to the use of melatonin for
      chronobiotic and hypnotic purposes, the literature seems to be unanimous
      concerning the efficacy and safety of melatonin, at least in the short-term, in
      cases where the secretion of melatonin is disrupted. In clinical applications the
      efficacy is assessed by compiling a 24-hour profile within which the moment of
      the nocturnal increase in secretion is compared to the time at which the patient
      is expected to fall asleep. So far not enough is known about the effects of long
      term use and about the interaction of melatonin with pubertal development. No
      consensus has yet been reached concerning the role of melatonin in the treatment
      of affective disorders. Recently there has been increasing interest in the
      effects of melatonin on seizures and the mechanism involved. CONCLUSION:
      Melatonin is a product with considerable potential provided it is administered in
      a controlled manner and the results are assessed accurately. At the moment it
      seems advisable to use melatonin only in clinical trials.

PMID- 16958195
TI  - [Bitter and gilded pills: psychiatry in the light (or shadow) of the
      pharmaceutical industry].
AB  - Psychotropic medication has brought about far-reaching changes in psychiatry: in
      its nature and practice, its image of man and its public image. Never before have
      so many psychotropic drugs been prescribed for young people. 'Difficult' children
      are now referred to as ADHD children and moody youngsters are given
      antidepressants. In adult psychiatry treatment is being dictated more and more by
      protocols and guidelines: very often medication is the treatment of choice. The
      reasons for this are largely economic. Increasingly 'research' is being sponsored
      by the pharmaceutical industry. Published research results are often skewed so as
      to favour the sponsor. Some scientific journals owe their survival to drug
      advertisements. Even some patient organisations are supported by the
      pharmaceutical industry. How will psychiatry and mental health care be able to
      escape from this 'straightjacket' in the future? The purpose of this polemical
      essay is to draw the attention of health care professionals and researchers to
      this rather worrying development.

PMID- 16958196
TI  - [The importance of public-private cooperation. Comment on Vandereycken].

PMID- 16958197
TI  - [Risks associated with parenteral treatment of acute agitation].
AB  - BACKGROUND: Acute agitation is a medical emergency requiring immediate
      intervention. However, treatment is a risky undertaking. AIM: To specify on the
      basis of a review of the literature: (1) the risks of (parenteral) interventions
      in psychiatric crisis situations; (2) to which antipsychotics these risks are
      linked; and (3) what precautionary measures and interventions are required.
      METHOD: A literature search was conducted using PubMed, using as key words:
      parenteral, antipsychotics, benzodiazepines, acute agitation, crisis
      intervention, and fatalities. RESULTS: Several parenteral antipsychotics are
      known to cause cardiotoxicity and/or hypotension. They can also induce acute
      movement disorders such as a laryngeal spasm. Benzodiazepines (parenteral) can
      lead to respiratory depression as a result of excessive sedation. CONCLUSION:
      Risks are associated with parenteral delivery of antipsychotics. These risks can
      be life-threatening. If an agitated patient needs to be given antipsychotics
      parenterally, the intervention should take place in surroundings where the
      patient can be adequately monitored and where the necessary facilities are
      available for dealing with life-threatening side effects.

PMID- 16958198
TI  - [Intakes for (day) clinical psychotherapy. A cohort study].
AB  - Little is known about the type of patient who is referred for clinical
      psychotherapy. A descriptive, retrospective cohort study was performed involving
      100 patients who attended a (day) clinic for personality, anxiety and eating
      disorders. Sociodemographic and clinical characteristics of these patients are
      described. Most of the patients had multiple disorders of a serious nature,
      displayed a high degree of functional impairment and were relatively treatment
      resistant. Of the 70% who were diagnosed as requiring treatment, 79% agreed to
      have the treatment that was offered.

PMID- 16958199
TI  - [Bipolar disorder and pregnancy; experiences from the practice].
AB  - Patients with bipolar disorder who become pregnant may develop an episode during
      their pregnancy, but an episode is much more likely to occur during the
      postpartum period. Three case histories show the kinds of problems that can
      arise. Risk factors are mentioned and advice is given about the best ways of
      preventing such problems.

PMID- 16958200
TI  - [Mirtazapine-induced dystonia in a patient with Alzheimer's disease].
AB  - A 79-year old female patient with Alzheimer's disease developed acute dystonia
      twelve hours after taking a single dose of mirtazapine 30 mg. Forty-five hours
      later the patient's dystonia began to subside and after sixty hours it had
      disappeared completely. This side-effect of mirtazapine is hardly mentioned in
      the literature. So far, little is known about the pathophysiology of acute
      dystonia and the possible role of mirtazapine. Some hypotheses and
      recommendations are proposed.

PMID- 16958201
TI  - [Reaction to "The psychiatrist in a split" and "Past the split"].

PMID- 16958202
TI  - [Reaction to "Imago"].

PMID- 16958204
TI  - The politics of science.

PMID- 16958203
TI  - Stem cells. The hope and the hype.

PMID- 16958205
TI  - The brawl in California.

PMID- 16958206
TI  - The big deals wheel again.

PMID- 16958207
TI  - Tour de testosterone.

PMID- 16958208
TI  - Why teens are obsessed with tanning.

PMID- 16958209
TI  - [Early marker of myocardial injury of the ischemia-reperfused heart in dogs and
      during operations with artificial circulation in humans].
AB  - The model of ischemia/reperfusion was reproduced on 9 unconscious dogs.
      Simultaneously with registration of indexes heart work, hemodynamic and
      mitochondrial factor (MF) in venous blood from right atrium was defined. Measures
      were done by spectrophotometria. We have also performed spectrophotometric
      determination of MF in 11 patients in course of operation with blood
      cardioplegia. Samples of mixed venous blood from the right atrium were taken on
      different stages of artificial blood circulation: ischemia and reperfusion.
      Besides that, patients' level of enzymes was defined: creatine kinase (CK), mv
      creatine kinase (mv-CK), lactatedehydrogenase (LDG), aspartataminotransferase
      (AST), within first day of postoperative period, and also ECG-recording within
      pre- and after operative period were done. Maximal MF level correlates with
      frequency and severity of cardiac rhythm disturbance, severity of myocardial
      hypoxia (r = 0.81). Maximum MF level also demonstrated correlation with KK (r =
      0.97), mvKK (r = 0.92), LDG(r = 0.81), AST (r = 0.85). Thus, in experimental and
      clinic conditions myocardial ischemia was accompanied by mPTP activation, which
      led to reperfusion myocardial injuries and to release of MF. Method of MF
      determination gives opportunity to propose its usage as early marker of ischemic
      injuries and also as marker of mPTP opening in vivo.

PMID- 16958210
TI  - [Diadenosine polyphosphate analogue modulates signal transduction in hippocampal
      slices].
AB  - The modulatory effect of endogenous diadenosine polyphosphates on synaptic
      transmission in the rat hippocampal slices has been re-examined with a non
      hydrolysable Ap4A analogue diadenosine-5',5'>>-P1,P4-[beta,gamma
      methylene]tetraphosphate (AppCH2ppA). We have shown that AppCH2ppA at low
      micromolar concentrations induce inhibition of orthodromically evoked population
      spikes, without affecting of excitatory postsynaptic currents and antidromic
      spikes recorded in the CA1 zone of hippocampus. Such a spatially selective
      neuronal inhibition may influence dendritic electrogenesis in pyramidal neurons
      and consequently mediate control of neuronal network activity in hippocampus.

PMID- 16958211
TI  - [Inhibitors of mitochondrial permeability transition pore prevent apoptosis of
      dopaminergic neurons in the mesencephalon].
AB  - In the study the role of apoptosis in development of dopaminergic neuronal cell
      death within substantia nigra (parts compacta) and ventral tegmental area induced
      by 6-OHDA was investigated. It was found that intermittent hypoxia and the water
      soluble vitamine E (Trolox) and melatonin, as antioxidants and inhibitors of
      mitochondrial permeability transition pore protect dopaminergic cells from
      cytotoxic effect of 6-OHDA. It is supposed that mitochondrial permeability
      transition pore plays an important role in apoptosis of neurons in the brain.

PMID- 16958212
TI  - [Effect of cytostatic ifosfamide on the function of the kidneys in white rats].
AB  - Influence of the single injection of iphosphomid on kidney function during 24
      hours after injection under functional loading (water and saline) was
      investigated. It was established that the single injection of iphosphomid to
      white rats led to changes of renal function manifested by decrease of creatinine
      clearence as well as tubular transport. It was shown that saline loading resulted
      in weakening of renal functional reserve accompanied by significant proteinuria,
      glucoseuria and disturbances of osmoregulation.

PMID- 16958213
TI  - [Dependence of electromyographic reaction indices of the muscles-antagonists and
      stiffness of the elbow joint on its extension velocity before and after the
      injection of neurotoxin].
AB  - Electromyographic (EMG) activity of the elbow joint muscles elicited by passive
      extension were recorded in anaesthetized cats before and after MPTP injection (7
      10 mg/kg intramuscularly). It was shown that after injection of such dose of MPTP
      amplitude and duration of the stretch-related M2-3 --components of EMG increased
      and recovered on 9-10 day after the chemical injection. Perturbation of an
      external extensor loading applied to the forearm with different velocities
      elicited m. biceps brachii EMG reactions which amplitude in norm correlated with
      a muscle stretch velocity and duration correlated with applied force duration.
      The MPTP injection led to reversible changes of these stretch-reflex parameters.
      In norm elbow joint stiffness showed a linear dependence on external loading
      velocity. The MPTP injection resulted in joint stiffness decrease during the
      quick perturbation of loading. The stiffness recovery was a longer process
      comparing to the EMG recovery. It is concluded that the evoked stretch reflex
      parameter changes as a result of artificially produced dopamine deficiency are
      insufficient for the total stiffness increase and rigidity manifestation and that
      amplitude and duration increase of stretch responses may come earlier than
      parkinsonian rigidity manifestation. It is supposed the decisive importance of
      supraspinal influences on rigidity development in dopamine function deficiency
      conditions.

PMID- 16958214
TI  - [Antioxidant modification of ionizing irradiation and additional stress effects
      on higher nervous activity in rats].
AB  - The aim of this study was to investigate the oxidative effect of the low-level
      radiation upon the higher nervous activity. Behavioral (shuttle-box) and
      statistical methods were used. The effect of the ionizing radiation (0.05 Gy)
      upon the indices of rats behavioral reaction as well as ability of some
      antioxidants (alpha-tocopherol, ascorbic acid, beta-carotene) used separately and
      in complex to diminish exposure effects on the indices studied have been
      investigated Beta-carotene demonstrated the largest protective effect alone and
      as a component in complex compound. Alpha-tocopherol used in animal exposured to
      the dose of 0.05 Gy, could case decline of the rats behavior reactions indices;
      this suggest that use of antioxidant therapy demands certain cautiousness. The
      results obtained suggest dominant role of the oxidant stress during ionizing
      radiation at least in dose of 0.05 Gy.

PMID- 16958215
TI  - [Influence of carbachol and atropine on the motor cortex neurons in cat operant
      reflex].
AB  - Effects of carbachol and atropine on the caused and background impulse neurons
      activity during operant reflex were studied on twenty motor cortex neurons. Motor
      cortex neurons in dependence of changes impulse neurons activity after carbachol
      administration have been divided into two groups; the first group includes
      neurons with a long influence on impulse activity and the second--with short.
      Carbachol applied by ionophoresis to motor cortex promoted authentic increase of
      background impulse activity and duration of the caused reaction in both groups.
      Abministration of atropine, an antagonist of m-cholinergic receptors
      significantly reduced parameters of background impulse activity and duration of
      the caused reaction. It was suggested that acetylcholine released by terminals of
      the cholinergic fibers in natural conditions takes part in maintenance of motor
      cortex neuron background activity and provides sufficient intensity of the motor
      commands generated by these cells; the given effects mediated by m-cholinergic
      receptors.

PMID- 16958216
TI  - [Effect of hydrocortison on the circadian rhythm of the kidney excretory function
      during long-term darkness].
AB  - In experiments on the white rats it was established that the steady-state (during
      8 days) darkness results in desynchronization of the circadian rhythms of kidney
      excretory function. Hydrocortisone hydrochloride 5 mg/kg during constant darken
      resulted in poluria, natriuresis and acidogenesis without influencing the acid
      phosphates excretion.

PMID- 16958217
TI  - [Genetically determined characteristics of conditioned reflex and locomotor
      activity of rats of different lines].
AB  - Peculiarities of conditioned instrumental food obtaining (getting) "pyrocmu"
      reflex development and realization of locomotor reactions (exploratory activity,
      motor activity, stance, gruming) of hypertensive (SHR) and Wistar rats in
      ordinary conditions and after strong sound signal were studied. It is shown that
      the dynamics of conditioned reflex development and its reproducing after
      experiment interruption are essentially different in two groups of animals:
      reflex conditioned in Wistar rats is of high level and is easily reproducible
      while in hypertensive animals it is transformed to the hidden (concealed) form of
      "incomplete" conditioned reflex-smelling at feeding rack in response to sound
      signal. The higher anxiety level and lower adaptability of hypertensive rats as
      compared with Wistar rats to the experimental conditions are confirmed by higher
      exploratory activity, more prolonged gruming in standard experimental conditions
      and long-duration immobility phase after sound signal.

PMID- 16958218
TI  - [Changes in the respiration function state and oxygen regimens in patients with
      insulin-dependent diabetes mellitus].
AB  - Changes of an oxygen supply system in type I diabetes mellitus patients of pre
      pubertal, pubertal and middle age were investigated. It is supposed that diabetes
      mellitus patients of pre-pubertal and pubertal age are the less resistant to
      hypoxic hypoxia. For the middle age patients oxygen concentration used could be
      considered as curative and could be applied in the interval hypoxic training
      course.

PMID- 16958219
TI  - [Sexual dimorphism of the psychophysiological indices in sportsmen of higher
      qualification].
AB  - To determine the influence of sexual dimorphism on mental characteristics in
      elite athletes, 24 sportsmen (18-27 years old) (17 men and 7 women members of
      Ukrainian National Judo Team), 20 sedentary men and 20 sedentary women (20-29
      years old) were studied. Results obtained confirmed significant difference of
      sexual dimorphism indices in athletes and sedentary people. It was determined
      that sexual dimorphism manifestations in athletes were as follows: (1) short
      memory capacity (62.58 +/- 3.21%) and coefficient of operational thinking (2.67
      +/- 0.16 standard units) was increased in women in comparison with men (55.78 +/-
      2.07% and 1.44 +/- 0.30 standard units, p < 0.05, accordingly), (2) on the
      contrary neurodynamic functions were decreased in women (latent time of simple
      (266.92 +/- 4.73 ms) and composite (494.44 +/- 6.38 ms) visual-motor reactions
      and power of nervous processes (18.49 +/- 8.93%) in comparison with men (239.62
      +/- 5.26 ms, 440.10 +/- 6.61 ms, 5.33 +/- 0.59%, p < 0.05, respectively). Results
      obtained indicate influence of sexual dimorphism on psychophysiological
      functions.

PMID- 16958220
TI  - [Types of physiological reactivity of the respiratory system and the features of
      physical work capacity in athletes].
AB  - On the basis researches of character responses of respiratory system (RS) on
      hypercapnic and physical load at 54 skilled athletes (the runners on 100, 800 and
      5000 m) are analyzed of the features in physiological reactivity of system on
      shifts respiratory homeostasis, reflecting a various orientation of long-term
      adaptation (sports of the training). The interrelation of sensitivity and
      stability of responses to hypercapnic (CO2-H+), and also limits and kinetic
      characteristics of responses RS of physical loads with manifestation of work
      capacity and mobilization features aerobic and anaerobic processes of during
      physical loads energy-supply was demonstrated. By means of tacsonomic analyses
      are allocated types of individual responses of organism of the skilled athletes
      on the basis of character RS responses to hypercapnic shifts in respiratory
      homeostasis. They in a high degree have been caused by sports specialization of
      athletes.

PMID- 16958221
TI  - [Oxidative stress and its role in carcinogenesis].
AB  - A review presents analysis of data on involving the oxygen active forms and
      products of lipid peroxidation resulted from oxidative stress in carcinogenesis
      at all its levels and during the treatment of cancer patients. Role of various
      classes of antioxidants in decrease of damaging effect of oxidative stress on DNA
      structure, state of plasmatic membrane and extracellular matrix as well as the
      prevention of development and progression of neoplasm is shown. The authors
      consider that use of antioxidants is well grounded during cytoreductive therapy
      in patients with various malignancies.

PMID- 16958222
TI  - [Mechanism of the buccal permeability of insulin].
AB  - Summary of theoretical and experimental data of insulin buccal permeability is
      presented in the article. The hypothetical mechanism of insulin buccal
      permeability which complies with published experimental data is proposed. The
      basic barriers for insulin before getting into blood through the mucous membrane
      of mouth are indicated and described. On the basis of the proposed hypothetical
      mechanism the application of surfactants for facilitating the buccal permeability
      of insulin is substantiated. The proposed mechanism will be useful for the
      development of new protein buccal preparations.

PMID- 16958223
TI  - [PI index value in fetal ductus venosus blood flow at 11-14 weeks in normal
      course of pregnancy].
AB  - OBJECTIVE: Development of ultrasound diagnostic with Doppler examination allows
      early and and more precise assessement of fetal anatomy and well-being. DESIGN:
      Evaluation of blood flow parameters in fetal ductus venosus between 11 and 14
      weeks of pregnancy was performed. MATERIAL AND METHODS: Fetal anatomy, nuchal
      translucency, nasal bone and ductus venosus blood flow has been studied with
      transabdominal probe in 225 consecutive fetuses according to Fetal Medicine
      Foundation recommendations. RESULTS: From total number of 225 cases finally ten
      women were excluded from analysis due to absent or reversed A-wave in DV blood
      flow. In remaining 215 cases mean value of PI was 0,94 (range 0,53-1,88), mean
      value of Vmax (S-wave) was 42,48cm/s (range 18,7-102,9cm/sek), and mean value of
      Vmin (A-wave)--11,91cm/s (range 1,13- 37,32 cm/sek). CONCLUSIONS: PI index value
      slightly decreased with increasing CRL. There was no differences in mean blood
      flow velocity with CRL for S-wave. A decrease in mean blood flow velocity with
      CRL was noted for A-wave.

PMID- 16958224
TI  - [Accuracy of weight prediction of full term newborns in ultrasonography].
AB  - OBJECTIVES: The estimation of prognostic value of ultrasonography in fetal weight
      assessment. DESIGN: Assessment of practical value of ultrasonography in full term
      newborns. MATERIAL AND METHODS: We have retrospectively analyzed the outcomes of
      611 ultrasonographic studies. It was divided into three groups: K, B, BD in
      relation to weight of newborns. According to that K group involved 302 newborns
      weighing between 2500-4000 g, B group 262 of newborns weighing more than 4000 g,
      BD group (47 cases) with weight exceeding 4500 g. Expected fetal weight were
      determined by using Shepard's algorithm. The single factor variance analysis with
      multiple coparison test was applied for assessment of mean errors of predicting
      fetal weight. RESULTS: The highest absolute value of error of expected weught of
      newborns occured in the group of the newborns wieghing more than 4500g in
      comparison with its real weight stated just after delivery (p<0,05). The
      underestimation of fetal weight appeared with incresing newborn weight (beta, 1
      BD groups). The overestimation of fetal weight was found in the group of the
      newborns between 2500-4000 g (p<0,05). CONCLUSIONS: The prognostic value of
      Shepard algorithm in predicting fetal weight is the most accurate for fetuses
      weighing between 2500-4000 g. The result of our study indicates U/S was the most
      useless for the newborns over 4500 g. Obstetricans should take into account other
      factors affecting fetal growth (maternal, paternal, environmental), especially
      with suspicion of fetal weight over 4500 g.

PMID- 16958225
TI  - [Fetal D gene in maternal plasma should be examined in all immunized Rh(-)
      pregnant women to avoid invasive procedures].
AB  - We have recently developed and published a noninvasive determination of fetal RhD
      status by examination of cell-free DNA in maternal plasma. The predictive value
      of the procedure of fetal testing, already published by us, was 99,6%. AIM: To
      assess the necessity of RhD fetal testing in immunized Rh(-) mothers with Rh(+)
      partners. MATERIAL: Rh(-) mothers with anti-D antibodies, their partners and
      children. METHODS: Molecular: RHD gene examination by real-time polymerase chain
      reaction; analysis of control genes present in the father but not in the mother.
      Serological: titre of anti-D antibodies, Rh phenotypes. RESULTS: Among 53 Rh(+)
      partners of immunized Rh(-) pregnant women, 56,6% were homozygous and 43,6%-
      heterozygous. The latter ones might have had either Rh(+) or Rh(-) children; in
      fact, in 52,2% of fetuses the D gene was not detected. Among fetuses of
      homozygous fathers (based on their phenotypes) 2 fetuses, to our surprise,
      occured to be Rh(-); however the subsequent genotyping showed that both fathers
      were heterozygous. The titres of anti-D in both groups of mothers with Rh(-) and
      Rh(+) fetuses were very similar. CONCLUSIONS: The examination of fetal D gene by
      noninvasive method should be performed in each alloimmunised Rh(-) mother if her
      partner is Rh(+). The prediction of RhD fetal status based on the fathers
      phenotype can be misleading, thus may result in unnecessary invasive method.

PMID- 16958226
TI  - [Clinical evaluation of periodontium in pregnant women with risk of preterm
      birth].
AB  - OBJECTIVES: The aim of the study was to evaluate condition of the periodontium in
      pregnant women with pathological progress of the pregnancy, clinically and to
      compare it to periodontium in pregnant women in good health. DESIGN: Over the
      last years, the studies have described that periodontitis caused by dental
      plaque, could be the risk factor for preterm birth and low birth weight.
      MATERIALS AND METHODS: This study was performed in 80 pregnant women, 40 with
      pathologic pregnancy and 40 with normal pregnancy in it. Periodontal Indexes were
      used to evaluate periodontium. RESULTS: In the searching group gingivitis
      gravidarum haemorrhagica diffusa and hyperplastica generalisata were dominating.
      In the control group gingivitis gravidatum simplex and hyperplastica localisata
      were observed. CONCLUSIONS: More severe manifestation of gingivitis gravidarum
      was noticed in pregnant women with risk of preterm low birth. We did not prove
      correlation between amount of bacterial dental plaque in pregnant women and risk
      of preterm low birth weight.

PMID- 16958227
TI  - [Problems in diagnosing breast cancer in women younger than 25 years old].
AB  - OBJECTIVES: There are several challenges in the diagnosis of breast cancer in
      young women. Special consideration must be given to the woman's fertility and
      body image issues, but the difficulty in distinguishing benign from malignant
      lesions in this group of patients still exists. The aim of our study was to show
      five cases of breast cancer in young women. MATERIALS AND METHODS: Based on 5
      cases of breast cancer in women younger than 25, several methods used in
      diagnosis in this group of patients were discussed. The role of USG and BAC was
      analyzed. Moreover, a significant role of RM and PET was emphasized. RESULTS:
      Diagnosing and treatment of young patients with breast cancer should be performed
      in specialized oncological centers experienced in dealing with breast cancer in
      very young women. CONCLUSIONS: 1. Because of the possibility of breast cancer in
      women under 25 years old, each case of breast tumor should be precisely
      diagnosed, especially by ultrasonography and biopsy (BAC) 2. Each case suspected
      of breast cancer in young women should be diagnosed in highly equipped and
      specialized medical center.

PMID- 16958228
TI  - [The preliminary evaluation of surgical treatment of pelvic organ prolapse with
      polypropylene mesh by double transobturator approch technique (double TOT)].
AB  - OBJECTIVES: The aim of this study was to evaluate preliminary results of a new,
      simple surgical technique with the use of polypropylene mesh (double TOT) used
      for the treatment of cystocele associated / not associated with urinary
      incontinence in females. MATERIAL AND METHODS: 19 women, aged 49-76, BMI 24-40,
      with cystocele associated or not with urinary incontinence, were operated on at
      the 1st Department of Obstetrics and Gynaecology in Warsaw, using double TOT
      technique. In this technique, described by Theobald, the trapezoidal
      polypropylene four-arm vaginal mesh is inserted through the obturator foramens
      from the outside to the inside and is positioned without tension under the
      urethra. RESULTS: 9 patients qualified for the operation were grade III in POPQA,
      5--grade IV, 4--grade II and one patient grade I. 16 women had additional
      operations performed beside double TOT. The duration of operations varied from 30
      to 135 minutes. No intra-operative complications were observed. There were no
      complications in short 6 weeks follow-up. CONCLUSIONS: Double Transobturator
      technique is simple, easy to learn, safe and, at the same time, efficient
      surgical procedure for the treatment of pelvic organ prolapse and female urinary
      stress incontinence. The results of longer follow-up on a larger group of
      operated patients will be more accurate.

PMID- 16958229
TI  - [Ferritin levels in the peritoneal fluid--a new endometriosis marker?].
AB  - Accumulating data suggests that iron homeostasis in the peritoneal cavity may be
      disrupted by endometriosis. Increased iron metabolism induce proinflammatory and
      prooxidative environment in the peritoneal fluid (PF), thus may be involved in
      the pathogenesis of the endometriotic disease. Ferritin, a protein consisting of
      24 subunits, may represent 25% of the total iron found in the organism. The aim
      of the study was to estimate the levels of ferritin in peritoneal fluid of women
      with endometriosis. MATERIALS AND METHODS: Forty women were studied, including 15
      patients with minimal/ mild endometriosis, 15 patients with moderate/ severe
      stage of the disease and 10 women without the disease. Ferritin concentrations
      were measured in the PF using a commercially available ELISA kit. RESULTS:
      Ferritin levels were significantly higher in PF from both women with stages I/II
      (p=0.003) and III/IV (p=0.0007) endometriosis as compared to the reference group.
      No significant difference in the PF ferritin levels was found between women with
      stages I/II and stages III/IV endometriotic disease (p=0.98). CONCLUSIONS:
      Increased ferritin levels, observed in peritoneal fluid, may reflect disrupted
      iron metabolism in the peritoneal cavity of endometriosis women.

PMID- 16958230
TI  - [Prenatal ultrasound findings in complete trisomy 9].
AB  - This case report describes a 40-year-old woman, primigravida. On 13,3 weeks of
      gestation we diagnosed an abnormal flow pattern in the umbilical artery and
      abnormal hyperechogenic structure in fetal abdomen. In next sonographic
      examination on 16 weeks of gestation we diagnosed ventriculomegaly and
      ahydramnion. We also observed spina bifida, hyperechogenic kidneys, abnormal flow
      pattern in the umbilical vein and pulmonary valve insufficiency. We performed
      genetic amniocentesis. We observed complete trisomy in cytogenetic examinations.
      The woman opted for an elective TOP according to the Polish Abortion Act on 20
      weeks of gestation.

PMID- 16958231
TI  - [Atopobium vaginae: characterization and association with pathogenesis of
      bacterial vaginosis].
AB  - Atopobium vaginae was described in 1999 by Rodriguez et al. It is a Gram-positive
      bacterium producing organic acids (lactic acid, acetic acid, formic acid) as a
      results of glucose fermentation. It was first found in vaginal swab taken from a
      healthy woman using 16S rRNA analysis. A. vaginae is associated with bacterial
      vaginosis and its consequences in upper part of women reproductive organs.

PMID- 16958232
TI  - [Role of inflammatory cytokines in male infertility].
AB  - Male infertility is a serious diagnostic problem and in many cases the exact
      cause of failure to reproduce remains unknown. New diagnostic methods are being
      evaluated in search of more precise diagnosis and possibility of casual
      treatment. Measuring the level of cytokines, both in seminal plasma and serum,
      does not only expand the diagnostic options, but also, through the growing
      knowledge of immune processes, can give rise to new therapeutic methods of
      improving the quality of semen and increasing the chance to reproduce. The
      article reviews the role of proinflammatory cytokines in its pathogenesis.

PMID- 16958233
TI  - Peri-operative anticoagulant therapy--the case for an uninterrupted dose-adjusted
      warfarin regimen in the high-risk patient.

PMID- 16958234
TI  - General surgery in crisis--the critical shortage.
AB  - INTRODUCTION: General surgery is facing a serious crisis. There has been a
      significant decline in the number of applicants for registrar posts and an
      inability to attract and retain general surgical specialists in the state sector.
      The Association of Surgeons of South Africa (ASSA) undertook this study to
      determine the extent and cause of the problem. METHODS: The study involved a
      combination of desk research and structured interviews. In addition, the Health
      Professions Council of South Africa (HPCSA) database was reviewed and compared
      with the South African Medical Association (SAMA) and ASSA databases. The medical
      schools provided information about student numbers and demographics, and the
      National Department of Health pro vided information about the status of medical
      practitioner and specialist posts in the state sector. RESULTS: Overall, 26.1% of
      the specialist posts were vacant. The situation was particularly critical in
      Mpumalanga and the Eastern Cape, where 84% and 58% of the specialist posts were
      vacant. Using a predictive model, a conservative estimate of the need for general
      surgeons was found to be at least 50 per year. Currently the eight medical
      schools graduate about 25 general surgeons per year. The changing demographics of
      medical students may be partly responsible for the decline in registrar
      applicants. CONCLUSION: The findings from this study have revealed that the
      shortage of general surgeons in the state sector has reached critical levels.

PMID- 16958235
TI  - General surgery in crisis--comparatively low levels of remuneration.
AB  - INTRODUCTION: Several factors, including comparatively low remuneration, may be
      responsible for the decline in applicants to general surgery. In this study, the
      levels of remuneration of general surgeons in the state sector were compared with
      other professionals in the state sector and general surgeons overseas. METHODS:
      The study involved a combination of desk research and structured interviews. The
      Paterson system of job evaluation was used to compare general surgeons with other
      professionals. The levels of remuneration of general surgeons in the state sector
      were compared with those of other professionals. RESULTS: There was a significant
      difference in the levels of remuneration between state-employed medical
      practitioners and other professional positions such as legal professionals,
      municipal managers and airline pilots. At senior levels (senior specialist) the
      remuneration was only +/- 55% of that paid to the selected comparator group.
      There was also a significant differential between the remuneration of state
      employed general surgeons and their overseas counterparts. CONCLUSION: Levels of
      remuneration of state-employed medical practitioners continue to lag behind other
      professionals.

PMID- 16958236
TI  - General surgery in crisis--factors that impact on a career in general surgery.
AB  - INTRODUCTION: The Association of Surgeons of South Africa (ASSA), because of a
      concern about the decline in the number of applicants for registrar posts,
      undertook this study into the various factors that may influence the choice of
      surgery as career option. METHODS: The study involved a combination of desk
      research and structured interviews with heads of departments, specialists, and
      registrars in general surgery. RESULTS: The reasons for choosing general surgery
      as a career included the immediately visible results of a surgeon's efforts and
      the practical and intellectual challenge of the specialty. General surgery
      continued to enjoy a high status in society. The greater focus on primary health
      care has affected facilities at tertiary and secondary institutions. General
      surgeons worked excessively long hours, which was associated with increased
      levels of stress and placed severe strains on family life. All respondents felt
      that their levels of remuneration were 'poor' in relation to other disciplines
      and professions. CONCLUSION: In this study we identified various factors that
      impacted either positively or negatively on the choice of general surgery as a
      career option.

PMID- 16958237
TI  - Autologous blood transfusion--a review.
AB  - The discovery of HIV and other transfusion-transmissible infections has increased
      the demand for alternatives to allogeneic blood transfusion. One such alternative
      is autologous transfusion. This review presents an analysis of autologous
      transfusion. We conclude that autologous transfusion should form part of a
      strategy to minimise the risk associated with allogeneic transfusion in Nigeria
      and other developing countries.

PMID- 16958238
TI  - Suprahyoid approach to base-of-tongue squamous cell carcinoma.
AB  - OBJECTIVE: To evaluate the suprahyoid approach to treatment of squamous cell
      carcinoma of the base of the tongue at Groote Schuur Hospital between 1999 and
      2004. DESIGN AND METHOD: Retrospective analysis was done of patients with base-of
      tongue squamous cell carcinoma treated using the suprahyoid approach. RESULTS:
      Seventeen patients underwent treatment for base-of-tongue squamous cell carcinoma
      utilising the suprahyoid approach. Complete medical records were available for 15
      of these patients. The most common presenting symptoms were neck mass (40%) and
      referred otalgia (33%). Alcohol was a risk factor in more patients (64%) than
      smoking (47%). Adverse pathological findings were present in less than 50% of
      patients (involved margins 20%, perineural invasion 40%, vascular invasion 33%).
      Functional outcome in terms of speech intelligibility was excellent and there
      were minimal swallowing problems, with most patients using compensatory
      strategies and dietary modification. There were 2 subsequent deaths (13%) as a
      result of distant metastasis and a second primary. CONCLUSION: The suprahyoid
      approach to treatment of base-of-tongue squamous cell carcinoma provides good
      exposure, local tumour control and excellent functional outcome.

PMID- 16958239
TI  - The relationship between diabetic retinopathy, glycemic control, risk factor
      indicators and patient education.
AB  - BACKGROUND: Hyperglycemia, high blood pressure and hypercholesterolemia are risk
      factors for diabetic retinopathy and vision loss in diabetic patients.
      OBJECTIVES: To evaluate risk factors in patients treated for diabetic retinopathy
      in our hospital clinic and assess patients' awareness of the impact of glycemic
      control; and to compare the findings with those in patients followed in a
      community clinic. METHODS: We performed a cross-sectional comparative study that
      included 178 consecutive patients with type 2 diabetes mellitus treated in the
      Retinal Vascular Service of Rabin Medical Center from 1 September to 31 December
      2004, and 107 consecutive patients with type 2 diabetes mellitus examined in a
      community clinic during the same period. A questionnaire was completed; the main
      outcome measures were glycemic and risk factor control and their correlation with
      diabetic retinopathy and visual acuity. RESULTS: Although only 43% of the
      patients had heard of HbA1c, 98% of them had undergone this analysis, with a mean
      level of 8.2% (SD 1.9) in the hospital patients and 7.7% (SD 1.6) in the
      community patients (P= 0.01, t-test). HbA1c was lower in hospital patients who
      were aware of the test. Correlations were found for visual acuity, diabetic
      retinopathy and laser treatment with HbA1c < or = 7%, cholesterol level < 200
      mg/dl and blood pressure < 130/85 mmHg. CONCLUSIONS: Since our study and previous
      reports have shown that HbA1c level < or = 7%, serum cholesterol level < 200
      mg/dl and blood pressure < 130/85 mmHg are associated with better preservation of
      vision in patients with type 2 diabetes mellitus, we propose that the
      ophthalmologist has a role in educating patients about glucose, lipid and blood
      pressure control as part of the treatment of diabetic retinopathy.

PMID- 16958240
TI  - The prevalence of reversible cardiovascular risk factors in Israelis aged 25-55
      years.
AB  - BACKGROUND: Coronary heart disease is a major cause of morbidity and mortality
      worldwide. Early detection of cardiovascular risk factors and intervention may
      reduce consequential morbidity and mortality. OBJECTIVES: To assess the
      prevalence of reversible and treatable cardiovascular risk factors among 26,477
      healthy Israeli adults: 23,339 men and 3138 women aged 25-55 years. METHODS: We
      collected data during routine examinations performed as part of a screening
      program for Israel Defense Force personnel. RESULTS: The three most prevalent
      cardiovascular risk factors were a sedentary lifestyle (64%), dyslipidemia
      (55.1%) and smoking (26.8%). Overall, 52.9% of the men and 48.4% of the women had
      two or more cardiovascular risk factors. Moreover, 52.4% of young adult men and
      43.3% of young adult women, age 25-34 years, had two or more reversible
      cardiovascular risk factors. CONCLUSIONS: In this expectedly healthy population
      there was a high prevalence of reversible and treatable cardiovascular risk
      factors in both genders and in young ages. These observations stress the need for
      routine health examinations and lifestyle modification programs even in the young
      healthy Israeli population.

PMID- 16958241
TI  - Predictors of left ventricular dysfunction in patients with first acute anterior
      myocardial infarction undergoing primary angioplasty.
AB  - BACKGROUND: The degree of left ventricular dysfunction determines the prognostic
      outcome of patients with acute myocardial infarction. OBJECTIVES: To define the
      clinical, angiographic and procedural variables related to LV dysfunction in
      patients with anterior wall AMI referred for primary percutaneous coronary
      intervention. METHODS: The sample included 168 patients treated by primary PCI
      for first anterior wall AMI. Clinical, demographic and medical data were
      collected prospectively into a computerized registry, and clinical outcome
      (death, reinfarction, major cardiovascular event) were evaluated during
      hospitalization and 30 days after discharge. Patients were divided into three
      groups by degree of LV dysfunction (mild, moderate, severe) and compared for
      clinical, angiographic and procedural variables. RESULTS: LV dysfunction was
      associated with pre-PCl renal failure (serum creatinine > 1.4 mg/dl), peripheral
      vascular disease, high peak creatine kinase level, longer door to balloon time,
      low TIMI flow grade before and after PCl, and use of an intraaortic balloon pump.
      On multivariate analysis adjusted for baseline differences, peak creatine kinase
      level (r = 0.3, P = 0.0001) and door to needle time (r = 0.2, P = 0.008) were the
      most significant independent predictors of moderate or severe LV dysfunction
      after anterior AMI. CONCLUSION: Abnormal LV function after first anterior AMI can
      be predicted by door to balloon time and the size of the infarction as assessed
      by creatine kinase levels. Major efforts should be made to decrease the time to
      myocardial reperfusion.

PMID- 16958242
TI  - Chorionic villous sampling: differences in patients' perspectives according to
      indication, ethnic group and religion.
AB  - BACKGROUND: The decision to undergo prenatal testing may be influenced by ethnic
      or religious factors. OBJECTIVES: To evaluate factors that might influence the
      decision of pregnant women to choose chorionic villous sampling for prenatal
      testing. METHODS: The study group comprised 239 women referred for prenatal
      diagnosis who elected to undergo CVS. The data were analyzed according to
      indication, ethnic group and religion. RESULTS: Among women undergoing CVS
      because of advanced maternal age and anxiety, we noted a significantly high
      proportion of unbalanced families, i.e., with three or more children of the same
      gender and deviated gender ratio. We found a significant excess of males among
      the Jewish families and a significant excess of females among the non-Jewish
      families. Jews were over-represented in the monogenic group while Christian Arabs
      were over-represented in the maternal age/anxiety group. CONCLUSIONS: The
      proportion of women who chose CVS for prenatal diagnosis varied according to
      indication, ethnic group and religion. The data in this study indicate that CVS
      may have been utilized for balancing families with > or = 3 or more children of
      the same sex. Christian Arabs chose CVS more often than the other groups. Jewish
      women may have utilized CVS for family balancing of both sexes, while non-Jews
      may have utilized CVS for balancing families with > or = 3 daughters.

PMID- 16958243
TI  - Secondary transfer of trauma patients: rationale and characteristics.
AB  - BACKGROUND: Trauma systems were created in order to provide optimal care for
      trauma patients. Hence, patients transferred to level I trauma centers are
      assumed to be transferred due to medical reasons as a result of complex injuries.
      OBJECTIVES: To explore the reasons for transfer of patients from regional to
      level I trauma centers in Israel as a basis for establishing a national policy
      regarding transfers. METHODS: The data on patients transferred to five level I
      trauma centers during a 6 month period were collected using a structured form.
      RESULTS: The study population comprised 929 patients transferred from regional
      hospitals. Most transfers were due to the need for a specialty unavailable at the
      first hospital (65%) or for special diagnostic equipment (3% in Jews, 23% in
      Arabs). Only 3.6% of the transferred patients were transferred because of multi
      system injury. Some casualties were transferred following their own request, 26%
      Jews and 3% Arabs. CONCLUSIONS: Most patient transfers concur with the
      recommendations of the Ministry of Health, namely, the absence of a certain
      specialty or equipment. The fact that many of the transfers reflect a lack of
      available resources at the first evacuation destination suggests that increasing
      the availability of these resources can help reduce secondary triage. It is
      recommended that a cost-benefit analysis be conducted.

PMID- 16958244
TI  - Cricotracheal resection for airway reconstruction: The Sheba Medical Center
      experience.
AB  - BACKGROUND: Intubation and tracheostomy are the most common causes of benign
      acquired airway stenosis. Management varies according to different conceptions
      and techniques. OBJECTIVES: To review our experience with cricotracheal resection
      and to assess related pitfalls and complications. METHODS: We examined the
      records of all patients who underwent CTR in a tertiary referral medical center
      during the period January 1995 to April 2005. RESULTS: The study included 61
      patients (16 women and 45 men) aged 15-81 years. In 17 patients previous
      interventions had failed, mostly dilatation and T-tube insertion. Complete
      obstruction was noted in 19 patients and stenosis > 70% in 26. Concomitant
      lesions included impaired vocal cord mobility (n=8) and tracheo-esophageal
      fistula (n=5). Cricotracheal anastomosis was performed in 42 patients,
      thyrotracheal in 12 and tracheotracheal in 7. A staged procedure was planned for
      quadriplegic patients and for three others with bilateral impaired vocal cord
      mobility. Restenosis occurred in six patients who were immediately revised with T
      tube stenting. Decanulation was eventually achieved in 57 patients (93.4%).
      Complications occurred in 25 patients, the most common being subcutaneous
      emphysema (n=5). One patient died of acute myocardial infarction on the 14th
      postoperative day. CONCLUSIONS: CTR is a relatively safe procedure with a high
      success rate in primary and revised procedures. A staged procedure should be
      planned in specific situations, namely, quadriplegics and patients with bilateral
      impaired vocal cord mobility.

PMID- 16958245
TI  - Canal expansive laminoplasty in the management of cervical spondylotic
      myelopathy.
AB  - BACKGROUND: Cervical spondylotic myelopathy is often progressive and leads to
      motor and sensory impairments in the arms and legs. Canal expansive laminoplasty
      was initially described in Japan as an alternative to the traditional laminectomy
      approach. The results of this approach have not previously been described in the
      Israeli population. OBJECTIVES: To describe the technique of CEL and present our
      clinical results in the management of patients with CSM due to multilevel
      compressive disease. METHODS: All patients undergoing CEL during the period 1984
      2000 were identified. Of these, 24 of 25 patients had complete clinical
      information. Mean follow-up was 18 months (range 4-48). Mean age was 60 years
      (range 45-72). One patient underwent CEL at three levels, 22 patients at four to
      five levels and 1 patient at six levels The primary outcome measure was
      improvement in spinal cord function (according to the Nurick classification).
      RESULTS: Twenty-three (96%) of the patients experienced relief of their symptoms.
      Of these, 11 patients showed improvement in their Nurick grade, 12 patients were
      unchanged and one had worsening. Intraoperative complications (epidural bleeding
      and dural tear) occurred in six patients. Two patients developed a late kyphosis.
      CONCLUSIONS: Our treatment of choice for multilevel CSM is canal expansive
      laminoplasty as initially described by Hirabayashi. It provides the ability for
      posterior surgical decompression without compromising the mechanical stability of
      the spine. This approach has the benefit of not requiring internal fixation and
      fusion. Our clinical outcome and surgical complication rate are comparable to
      those in the literature.

PMID- 16958246
TI  - Physicians underdiagnose and undertreat obesity in ishemic heart disease
      patients: data from the HOLEM Study Group.
AB  - BACKGROUND: Obesity is an independent risk factor for ischemic heart disease and
      affects the status of other risk factors for cardiovascular disease. OBJECTIVE:
      To study the attitude of physicians to obesity by examining discharge letters of
      overweight patients with ischemic heart disease. METHODS: We used the HOLEM
      database for this analysis. The HOLEM project was designed to study the NCEP
      (National Cholesterol Education Program) guideline implementation among patients
      with IHD at hospital discharge. We documented the recording of risk factors and
      treatment recommendations for IHD by reviewing the discharge letters of 2994 IHD
      patients admitted to four central hospitals in Israel between 1998 and 2000. A
      follow-up visit was held 6-8 weeks after discharge, at which time the diagnosis
      of IHD was verified, risk factor status was checked, height and weight were
      measured and drug treatment was reviewed. RESULTS: Mean body mass index was 28.3
      kg/m2 and 32% were obese (BMI > or = 30 kg/m2). Only 39.6% of the obese patients
      and 65.8% of the morbidly obese patients (BMI > or = 40 kg/m2) had "obesity"
      noted in their discharge letters, and weight loss recommendation was written in
      only 15% of the obese patients' discharge letters. Acute episodes like acute
      myocardial infarction and unstable angina did not influence the notation of
      obesity, and only BMI and the number of additional risk factors were positively
      correlated with the notation of this risk factor. CONCLUSIONS: Despite the
      importance of obesity, weight status was not noted and weight loss was not
      recommended in most of the discharge letters of obese IHD patients.

PMID- 16958247
TI  - Introducing co-payment for consultant specialist services.
AB  - BACKGROUND: Full medical coverage may often result in overuse. Cost-sharing and
      the introduction of a co-payment have been shown to cause a reduction in the use
      of medical services. OBJECTIVES: To assess the effects of the recently introduced
      co-payment for consultant specialist services on patient utilization of these
      services in southern Israel. METHODS: Computerized utilization data on specialist
      services for 6 months before and 6 months after initiation of co-payment were
      retrieved from the database of Israel's largest health management organization.
      RESULTS: A decrease of 4.5% was found in the total number of visits to Soroka
      Medical Center outpatient clinics and 6.8% to community-based consultants. An
      increase of 20.1% was noted in the number of non-actualized visits to the
      outpatient clinics. A decrease of 6.2% in new visits to hospital outpatient
      clinics and 6.5% to community clinics was found. A logistic regression model
      showed that the residents of development towns and people aged 75+ and 12-34 were
      more likely not to keep a prescheduled appointment. CONCLUSION: After
      introduction of a modest co-payment, a decrease in the total number of visits to
      specialists with an increase in "no-shows" was observed. The logistic regression
      model suggests that people of lower socioeconomic status are more likely not to
      keep a prescheduled appointment.

PMID- 16958248
TI  - Estimating the usual prevalence and incidence of acute illness in the community:
      implications for pandemic influenza and bioterrorism preparedness.
AB  - BACKGROUND: Early clinical signs of influenza caused by a pandemic strain will
      presumably not differ significantly from those caused by other respiratory
      viruses. Similarly, early signs of diseases that may result from bioterrorism are
      frequently non-specific and resemble those of influenza-like illness. Since the
      time window for effective intervention is narrow, treatment may need to be
      initiated prior to a definitive diagnosis. Consequently, planning of medications,
      manpower and facilities should also account for those who would be treated for an
      unrelated acute illness. OBJECTIVES: To estimate usual patterns of acute illness
      in the community as a baseline for integration into pandemic influenza and
      bioterrorism preparedness plans. METHODS: Between 2000 and 2003 we conducted 13
      telephone surveys to estimate the usual incidence and prevalence of symptoms of
      acute illness in the community. RESULTS: On average, 910 households were included
      in each of the surveys, representing about 3000 people. The compliance rates for
      full interviews ranged from 72.3% to 86.0%. In winter, on average, about 2% of
      the Israeli population (individuals) suffered each day from fever of > or = 38
      degrees C, and about 0.8% during the other months. The prevalence of cough was
      higher, 9.2% in winter and 3% during summer. Daily incidence of fever ranged from
      about 0.4% per day in winter to about 0.2% in the fall. The prevalence and
      incidence of both fever and cough were highest for infants followed by children
      aged 1-5 years. CONCLUSIONS: These background morbidity estimates can be used for
      planning the overall treatment requirements, in addition to actual cases
      resulting from pandemic influenza or a bioterrorist incident.

PMID- 16958249
TI  - The role of the ophthalmologist in educating the diabetic patient.

PMID- 16958250
TI  - Cardiovascular risk factors in young adults--are we neglecting the next
      generation?

PMID- 16958251
TI  - Human embryonic stem cells for vascular development and repair.
AB  - Embryonic stem cells, derived from the inner cell mass of embryos in the
      blastocyst stage, are cells capable of perpetual self-renewal and long-term
      propagation and hold the potential to differentiate to progeny of the three
      embryonic germ layers. Since their derivation approximately two decades ago,
      exploration of mouse ES cells made major advances in ES cell differentiation
      research and in the successful development and propagation of various cell types.
      The subsequent derivation of ES cells from human embryos allows detailed study of
      early developmental events practically unreachable in early human embryos, and
      the potential derivation of a variety of adult cell types differentiated from the
      ES cells holds immense therapeutic promise. Recently, the study of ES cell
      derived teratomas identified the partial presence of human ES cell-derived
      premature vessels within the teratoma, and a preliminary protocol for the in
      vitro derivation of a vascular progenitor was developed based on the study with
      the mouse ES cells. Furthermore, genetic profiling identified a pattern of
      expression of various endothelial and vascular smooth muscle cell genes that
      provide additional information on the degree of vascular development that ES
      cells undergo. Finally, the clinical application of ES cells in transplantation
      medicine is closer than ever following the affirmation that human ES cell-derived
      endothelial progenitors conferred increased neovascularization in transplanted
      engineered skeletal muscle. This review summarizes these recent advances in
      vascular development from human ES cells and their potential clinical
      applications.

PMID- 16958252
TI  - Thyrotoxic hypokalemic periodic paralysis in a Philippine man.

PMID- 16958253
TI  - Non-classical Kawasaki disease in a 2 month old infant.

PMID- 16958254
TI  - Reactivation of cytomegalovirus in critically sick patients.

PMID- 16958255
TI  - Hepatic hemangloendothelioma: the need for early diagnosis and resection.

PMID- 16958256
TI  - Eosinophilic esophagitis.

PMID- 16958257
TI  - Darier's disease.

PMID- 16958258
TI  - Nematode parasites of Clarias gariepinus (Burchell, 1822) from the Rietvlei Dam,
      South Africa.
AB  - Catfish, Clarias gariepinus, from the Rietvlei Dam near Pretoria, South Africa
      were examined for nematode parasites. Two species, Procamallanus laeviconchus in
      the stomach and Contracaecum spp. larvae in the abdominal cavity, were found. The
      morphology of these species, based on light and scanning electron microscopy, and
      how they compare with previously described specimens are discussed. Infection
      rates were mild compared to previous surveys although Contracaecum spp. had a
      high prevalence of 86%.

PMID- 16958259
TI  - Observations on mass production of Calicophoron microbothrium metacercariae from
      experimentally and naturally infected Bulinus tropicus.
AB  - In an attempt to establish an ideal method for mass production of Calicophoron
      microbothrium metacercariae, a study was carried out to compare the shedding
      capacities of Bulinus tropicus naturally and experimentally infected with C.
      microbothrium. A total of 906 F1 B. tropicus between 4 and 5 weeks old were each
      experimentally infected with two C. microbothrium miracidia and monitored for 12
      weeks. The infected snails were fed on dried lettuce and fish flakes and were
      kept in 1 l plastic aquaria housed in a snail room where temperature, light and
      humidity were controlled. Seventy-four percent of the experimentally infected
      snails died during the prepatent period and of the remaining, only 13.2%
      developed patent infection, while 12.5% were refractory. Snail growth rate was
      poor and the average shedding rate was 20 cercariae per snail per day. Compared
      to the experimentally infected snails, 2200 adult B. tropicus, collected from the
      field and naturally infected with C. microbothrium, yielded high numbers of
      metacercariae. Eighty-four percent of the snails died within 7 weeks of the study
      with peak mortality occurring from the 2nd to the 4th week of infection and
      coinciding with an overall decrease in the number of cercariae shed.

PMID- 16958260
TI  - On cestode and digenean parasites of Clarias gariepinus (Burchell, 1822) from the
      Rietvlei Dam, South Africa.
AB  - Sharptooth catfish, Clarias gariepinus, from the Rietvlei Dam near Pretoria,
      South Africa were examined for internal platyhelminth parasites. Two adult
      cestodes, Polyonchobothrium clarias (stomach) (prevalence 71%, mean intensity =
      5, n = 7) and Proteocephalus glanduliger (anterior intestine) (prevalence 14%,
      mean intensity = 2, n = 7), were found in the gut while metacercariae of one
      larval digenean, Ornithodiplostomum sp. (prevalence 14%, mean intensity = 140, n
      = 7), were found encysted in the muscles. The morphology of these species, based
      on light and scanning electron microscopy as well as histological analysis, and
      how they differ from previously described specimens, are discussed.
      Ornithodiplostomum is a new record in southern Africa. Infection levels of the
      host fish were mild compared to records from previous surveys.

PMID- 16958261
TI  - Gastric nematodes of nile crocodiles, Crocodylus niloticus Laurenti, 1768, in the
      Okavango River, Botswana.
AB  - The ascaridoid nematodes Dujardinascaris madagascariensis Chabaud & Caballero,
      1966, Dujardinascaris dujardini (Travassos, 1920), Gedoelstascaris vandenbrandeni
      (Baylis, 1929) Sprent, 1978 and Multicaecum agile (Wedl, 1861) Baylis, 1923 were
      recovered from the stomach contents of Crocodylus niloticus Laurenti, 1768 from
      the Okavango River, Botswana, together with Eustrongylides sp., a dioctophymatoid
      nematode usually parasitizing piscivorous birds. Dujardinascaris madagascariensis
      was present in most of the infected hosts, while the remaining species were
      mostly represented in single collections in one to three hosts. All four
      ascaridoid nematodes represent new geographic records.

PMID- 16958262
TI  - Ethnoveterinary medicine practices among Tsonga speaking people of South Africa.
AB  - Rapid Rural Appraisal methods were used to collate and code the indigenous
      knowledge on animal healthcare of Tsonga speaking people of South Africa. There
      was a rapport between local disease names as described by their clinical signs by
      the farmers and the local veterinary services important disease list. The
      perceived causes of diseases were physico-biological elements and no reference to
      ancestral guidance was recorded. Males and old people were more knowledgeable but
      females and young people did show a certain degree of confidence during general
      discussions. Plants were more frequently used than other non-conventional
      remedies with cattle being the most treated animals. Farmers reported using 19
      plant species belonging to 12 families. Plants were collected from the wild when
      needed and no specific storage system was used. They were administered as
      decoctions or infusions of single plants. These remedies were used not only as
      alternatives to expensive pharmaceutical products but also because in certain
      diseases or chronic cases, they were thought to be more efficacious.

PMID- 16958263
TI  - Birds as hosts of immature ixodid ticks in Free State Province, South Africa.
AB  - The objective of this study was to determine the species spectrum of ixodid ticks
      infesting birds in Free State Province, South Africa. To this end a large number
      of birds belonging to several species were examined for ticks and a total of 180
      birds belonging to 39 species at 17 localities were infested, and ticks belonging
      to eight species were recovered. The immature stages of only two, namely
      Amblyomma marmoreum and Hyalomma marginatum rufipes, were sufficiently prevalent
      and numerous to safely assume that they regularly use birds as hosts. Helmeted
      guineafowls, Numida meleagris, were the most heavily infested and one harboured a
      total of 319 larvae and four nymphs. Amongst the other species an eastern clapper
      lark, Mirafra fasciolata, was infested with 69 larvae and a nymph, but no other
      bird harboured more than 40 ticks. The larvae and nymphs of H. m. rufipes were
      most numerous on birds from April to August.

PMID- 16958264
TI  - Immunoreactivities to protein gene product 9.5, neurofilament protein and neuron
      specific enolase in nerves in the oviduct of the sexually immature ostrich,
      Struthio camelus.
AB  - The present study investigated the distribution of nerves in the oviduct of the
      sexually immature ostrich. The presence of protein gene product 9.5,
      neurofilament protein and neuron specific enolase nerve fibres were demonstrated
      in the infundibulum, magnum, isthmus, shell gland and vagina. Nerve fibres
      containing protein gene product 9.5, neuron specific enolase and neurofilament
      protein were particularly numerous in the tunica muscularis and intermuscular
      connective tissue areas of the shell gland and vagina. The presence of a large
      number of nerves in these oviductal regions is probably important in the
      coordination of muscle contraction. An interesting finding of the study was the
      presence of protein gene product 9.5 and neuron specific enolase immunopositive
      nerve fibres in the walls of blood vessels. It is likely that these nerves are
      autonomicin nature and play a role in the regulation of blood flow. This study
      has shown the presence of an extensive neural network in the oviduct of the
      ostrich. In addition, the results of the investigation have shown that the
      neuronal markers protein gene product 9.5, neurofilament protein and neuron
      specific enolase can be used to demonstate nerve fibres in the ostrich.

PMID- 16958265
TI  - Gross pathological findings in sows of different parity, culled due to recurring
      swine urogenital disease (SUGD) in Kenya.
AB  - In a large Kenyan production unit the urogenital organs and mammary glands of 771
      sows, culled due to recurring swine urogenital disease (SUGD) were subjected to
      necropsy Necropsy findings were analysed separately according to parity group of
      the sows [parities 2 (n = 252); 3-5 (n = 250); and > 5 (n = 269)]. Sows of higher
      parities had more pathological changes in their ovaries, uteri, vaginas,
      cervices, urinary bladders, kidneys and mammary glands compared to parity 2 sows
      (P < 0.05 and P < 0.01, respectively). Parity 2 sows had more ovarian
      degeneration, mucosal hyperaemia, congestion in the bladder, and acute purulent
      exudative mastitis than parity > 5 sows (P < 0.05 and P < 0.01, respectively).

PMID- 16958266
TI  - A serological survey for antibodies to foot-and-mouth disease virus in indigenous
      Tswana goats and sheep in Kasane, Maun and Shakawe districts in northwestern
      Botswana.
AB  - A serological survey was conducted in apparently healthy, unvaccinated indigenous
      Tswana goats and sheep in Kasane, Maun and Shakawe districts in northwestern
      Botswana in order to determine in these animals, the levels of exposure to the
      South African Territories (SAT) serotypes: SAT 1, SAT 2 and SAT 3 of foot-and
      mouth disease virus (FMDV). A total of 250, 142 and 134 goat sera originating
      respectively from Kasane, Maun and Shakawe districts were tested for FMDV
      antibodies against the three SAT serotypes by the liquid phase blocking enzyme
      linked immunosorbent assay and 26 of 250 (10.4%), 5 of 142 (3.5%) and 18 of 134
      (13.4%) were positive either to SAT 1 or SAT 3, or to both serotypes. None of the
      goats' sera was positive to SAT 2 serotype. All sheep sera (n = 9) tested
      negative against all three serotypes of the virus. The findings are discussed in
      relation to results of other serological surveys carried out elsewhere.

PMID- 16958267
TI  - The fluorescent detection of Paradiplozoon sp. (Monogenea: Diplozoidae)
      attachment clamps' sclerites and integumental proteins.
AB  - In the genus Paradiplozoon, few hard structures are present therefore most of the
      taxonomic studies have focused on the unique ultrastructure of the sclerites.
      Alcohol-fixed specimens were transferred to BSA-saline for 5 min. before staining
      indefinitely with 5 microl WGA-TRX, 5 microl SYTO 9 and 5 microl of Calcofluor
      White M2R. Rhodamine, Fluorescein and DAPI bandpass filters on the microscope
      enabled selective light wavelength illumination of the three flourochromes by a
      mercury light source. This method provided an easy and rapid methodology to show
      the internal sclerites of attachment clamps. It is suitable for alcohol preserved
      specimens and may have additional applications in other helminth organisms.

PMID- 16958268
TI  - Treatment of natural ovine malignant theileriosis with a chloroform extract of
      the plant Peganum harmala.
AB  - One hundred sheep naturally infected with Theileria lestoquardi were treated with
      a chloroform extract of the plant Peganum harmala. The treatment was continued
      for 5 days, the dose of extract being 5 mg/kg per day. Sixty-five of the sheep
      responded to treatment and recovered but 35 did not and died. The cure rate was
      65%.

PMID- 16958269
TI  - Cloned Theileria parva produces lesser infections in ticks compared to uncloned
      T. parva despite similar infections in cattle.
AB  - Experimental transmissions of cloned Theileria parva in cattle with Rhipicephalus
      appendiculatus ticks were compared to transmissions with uncloned T. parva during
      studies on the potential for genetic recombination during syngamy of Theileria to
      produce antigenic diversity for evasion of bovine immunity. Prevalence and
      abundance of T. parva infection in adult ticks, which resulted from the feeding
      of nymphs on the calves, were significantly higher in the uncloned compared to
      the cloned T. parva. Development of sporoblasts of T. parva in the ticks to
      produce infective sporozoites was similar. There was no statistically significant
      difference in the clinical course of infection in cattle between cloned and
      uncloned T. parva. It was concluded that cloned T. parva has characteristics that
      reduce its viability during the tick stages of its life cycle.

PMID- 16958270
TI  - 10 PCs stolen at HCA office.

PMID- 16958271
TI  - Charitable obligations. Both sides declare victory in uninsured billing
      settlements. Will more systems settle rather than fight it out in court?
AB  - Some not-for-profits involved in uninsured billing lawsuits have decided to
      settle the cases rather than pay hefty legal fees to fight in court. But
      hospitals contend offering discounts to the uninsured won't make much of a
      difference since most don't pay anyway. Attorney John Phillips, left, says the
      fact poor people don't have the money to pay is really the impetus behind these
      lawsuits.

PMID- 16958272
TI  - The CMS giveth ... and it taketh away. Specialty hospital developers celebrate
      end of ban. Physicians, ASCs are big losers in proposed PPS plan.

PMID- 16958273
TI  - A data quagmire? Privacy concerns raised about Blues database launch.

PMID- 16958274
TI  - Kaiser going consumer-driven. Largest HMO gearing up for HSAs, expansion.

PMID- 16958275
TI  - Aramark assures clients. But deal could be chance for rivals to seize share.

PMID- 16958276
TI  - Nurses target AHA. HQ picketed over stand in charge nurse case.

PMID- 16958277
TI  - Charge clouds Tenet results.

PMID- 16958278
TI  - HCA's magic act. Going private hinges on unlikely bid to make a mountain of debt
      vanish.

PMID- 16958279
TI  - There's no gain in gain-sharing. Savings on surgical devices pale in comparison
      to benefits of advanced procedures.

PMID- 16958280
TI  - Are hospitals next in line? Government investigators probing relationships
      between physicians, devicemakers may soon train sights on hospitals.

PMID- 16958281
TI  - Price-fixing allegations. Orthopedic devicemakers targeted.

PMID- 16958282
TI  - Embedded trouble. Link in software inherited through acquisition left patient
      data vulnerable.

PMID- 16958283
TI  - AAFP pushing technology. New program could boost quality; cut down on waste.

PMID- 16958284
TI  - Relationship between degree of polymerization and enamel bonding strength with
      self-etching adhesives.
AB  - PURPOSE: To investigate the relationship between the degree of conversion of
      double bonds of all-in-one adhesives and their shear bond strength on ground
      human enamel. MATERIALS AND METHODS: Six commercially available systems and one
      experimental adhesive were tested: Absolute (ABS; Dentsply-Sankin), Clearfil S3
      Bond (CSB; Kuraray), G-Bond (GBO; GC), Hybrid Bond (HYB; Sun Medical), iBond
      (IBO; Heraeus Kulzer), Xeno IV (XEN; Dentsply Caulk), and experimental iBond NG
      (ING; Heraeus Kulzer). Conventional shear bond strengths (SBS, n=8) of adhesive
      coated enamel specimens bonded to Venus composite (Heraeus Kulzer) and degrees of
      conversion (DC) (FTIR, n=5) were determined after 1 and 10 min, 1, 2, and 24 h of
      storage. Data were statistically analyzed using ANOVA and Duncan's post hoc test
      (0 < 0.05). RESULTS: The adhesives' SBS (MPa) and DC (%) by testing time followed
      logarithmic regression lines established by the least square method. Mean shear
      bond strengths after 1 min/24 h were: ABS 9.8/14.9; CSB 14.7/23.4; GBO 14.8/22.0;
      HYB 9.7/17.0; IBO 11.3/22.3; XEN 9.1/17.3; ING 9.7/25.6. The corresponding mean
      DC values were: ABS 51.3/66.2; CSB 83.1/90.8; GBO 75.8/87.7; HYB 49.6/67.2; IBO
      72.6/93.7; XEN 61.6/74.1; ING 64.9/89.1. Linear regressions for the relationship
      DC vs. SBS were significant with coefficients of determination (r2) between 0.72
      and 0.97. CONCLUSION: Despite similar acidity, the adhesives showed different
      SBSs on enamel. Based on the relationships between DC and SBS, the cohesive
      failure patterns observed, and the composition-property relations discussed, it
      is concluded that the percentage DC is the main parameter influencing an
      adhesive's bonding efficacy to ground enamel.

PMID- 16958285
TI  - Influence of radiation on bond strength.
AB  - PURPOSE: The aim of this in vitro study was to evaluate the shear bond strength
      of two adhesive systems--Prime & Bond NT (PBNT) and Clearfil SE Bond (CSEB)--to
      dentin irradiated before or after adhesive application. MATERIALS AND METHODS:
      Thirty extracted molars were sectioned mesiodistally with a diamond bur. The
      inner surface of each tooth's dentin was ground flat with SiC abrasive papers.
      The roots of the sectioned teeth were mounted in a cylindrical mold using
      chemically cured acrylic resin. In groups A1 and B1, a radiation dose of 60 Gy
      (R) was applied to the dentin surfaces at this point. In all groups, adhesives
      were applied according to the respective manufacturer's instructions. Cylindrical
      composite resin restorations (CRR; internal diameter 3 mm, height 4 mm) were then
      placed on the center of the flattened dentin surfaces. At this point, groups A2
      and B2 received 60 Gy of radiation, and groups C1 and C2 remained as
      nonirradiated controls. Thus, the test groups were: A1: R + PBNT (Primed Bond NT)
      + CRR; A2: PBNT + CRR + R; B1: R + CSEB (Clearfil SE Bond) + CRR; B2: CSEB + CRR
      + R; C1: PBNT+ CRR; C2: CSEB+ CRR. Specimens were mounted in a universal testing
      machine and shear load was applied at a crosshead speed of 1 mm/min until
      failure. Bond strength values were calculated as MPa and the results were
      evaluated statistically using repeated measures of two-way ANOVA, with
      significance set at p < 0.05. RESULTS: Irradiation significantly affected
      adhesion of composite to dentin in groups A1 and A2 (p = 0.002). Group A1 showed
      statistically lower bond strength than group A2 (p < 0.05). No statistically
      significant differences were found among the other groups (p = 0.49). CONCLUSION:
      The time point of irradiation can have an adverse effect on bond strength,
      depending on the type of adhesive material.

PMID- 16958286
TI  - Marginal adaptation of composite restorations photoactivated by LED, plasma arc,
      and QTH light using low-modulus resin liners.
AB  - PURPOSE: The aim of this study was to evaluate the influence of resin liners on
      the marginal adaptation to dentin of resin composite restorations photoactivated
      by a conventional quartz-tungsten halogen lamp (QTH), light emitting diodes
      (LED), and a plasma arc light (PAC). MATERIALS AND METHODS: The buccal surfaces
      of 120 bovine incisors were ground until a flat dentin area was obtained. A
      circular cavity (4 mm in diameter x 1.5 mm in depth) was prepared in this area.
      Scotchbond Multi Purpose was applied in the cavities following the manufacturer's
      instructions. The specimens were randomly assigned into 4 groups according to the
      lining technique: (1) control (1 adhesive layer); (2) three adhesive layers; (3)
      Filtek Flow; (4) Protect Liner F. Each group was further divided into 3 subgroups
      according to the light-curing method: (A) QTH; (B) LED; (C) PAC. All cavities
      were then restored with a single increment of Filtek Z250 restorative composite
      and polished. Caries Detector was applied to each specimen for 5 s. Images of dye
      stained gaps were observed under a stereomicroscope and transferred to a computer
      measurement program. Gap values were obtained by dividing the dyed margin length
      by the total cavity length, then multiplying by 100. Data were analyzed using
      ANOVA and Tukey's test (p < 0.05). RESULTS: All the tested lining techniques
      significantly decreased marginal gap formation when compared with the control
      group only for the QTH light groups. There was no significant difference among
      the light-curing methods. CONCLUSION: The use of resin liners can effectively
      reduce the gap formation along dentin margins, but only when QTH light is used.

PMID- 16958287
TI  - Compatibility between an all-in-one self-etching adhesive and a dual-cured resin
      luting cement.
AB  - PURPOSE: To determine if bonding incompatibility between a single-step self
      etching adhesive and a dual-cured luting cement is prevented by addition of
      deprotonizing anion exchange resin powder to the amine component of the resin
      cement. MATERIALS AND METHODS: iBond adhesive (IBO) (Heraeus Kulzer) and the dual
      cured resin cement Twinlook (TWI) (Heraeus Kulzer) were used with base pastes,
      containing 0, 1, 2, and 4 wt% anion exchange resin (AER) in OH- form.
      Conventional shear bond strength (SBS) was determined on human dentin. After
      application of IBO, a cylindrical mold was clamped on the treated surface and
      bulk filled with TWI. SBS was measured after 24 h in 37degrees C water at a
      crosshead speed of 1 mm/min. The following curing protocols were investigated:
      Group 1: IBO not light cured, TWI redox cured; group 2: IBO light cured, TWI
      redox-cured; group 3: IBO light cured, TWI dual cured (n=8). The data were
      statistically analyzed using ANOVA and Duncan's post-hoc test at alpha < 0.05.
      RESULTS: The mean SBSs (MPa) with original TWI in groups 1, 2, and 3 were 12.7aA,
      16.4bA, and 24.7cA. The corresponding figures for 1% AER were: 16.6aB, 23.0bB,
      22.8bA; for 2% AER: 16.8aB, 22.6abB, 24.6bA; and for 4% AER: 16.2aAB, 22.5bB,
      24.7bA. Different small and capital letters denote significant differences by
      treatment group and by AER content, respectively. CONCLUSION: Addition of anion
      exchange resin to the amine component of the dual-cured resin cement enhances the
      bond strength to dentin upon redox curing by prevention of amine neutralization
      through functional acid monomers from an all-in-one adhesive, mainly when the
      adhesive or the luting cement were not light cured.

PMID- 16958288
TI  - Shear bond strength of glass-ionomer cements to air-abraded dentin.
AB  - PURPOSE: The aim of this in vitro study was to evaluate the shear bond strength
      of two conventional glass-ionomer cements to bovine dentin when using the air
      abrasion technique for cavity preparation. MATERIALS AND METHODS: Forty bovine
      central incisors were selected, embedded in polyester resin, and ground until the
      dentin surface was exposed. The teeth were randomly assigned to four groups: I
      and II--rotating instrument with a carbide bur; III and IV--an air-abrasion
      system. Groups I and III were restored with Fuji IX and groups II and IV with
      Ketac Molar. A 3-mm-diameter bonding site was delimited and treated with 10%
      polyacrylic acid for 10 s in the Fuji IX subgroups and with 25% polyacrylic acid
      for 10 s in the Ketac Molar subgroups. After surface treatment, a glassionomer
      cylinder was prepared for each specimen, using a split bisected Teflon matrix.
      The finished specimens were submitted to the shear bond strength test in a
      universal testing machine at a crosshead speed of 0.5 mm/min. The data were
      analyzed using ANOVA and Scheffe statistical tests. The dentin bonding areas were
      analyzed under a stereoscopic optical magnifier (40X) to assess the type of
      failure. RESULTS: The mean (SD) shear bond strengths in MPa were: group I--3.49
      (+/- 3.77), group II--7.17 (+/- 2.93), group III--7.55 (+/- 2.99), group IV--5.67
      (+/- 3.90). Ketac Molar showed higher bond strength values in bur-prepared
      cavities, while on the air-abraded preparations, Fuji IX showed superior results.
      CONCLUSION: It can be concluded that the air-abrasion system used for cavity
      preparations may influence the bonding performance of conventional glass-ionomer
      cements to dentin.

PMID- 16958289
TI  - An investigation of the interfacial strengths of methacrylate resin-based glass
      fiber post-core buildups.
AB  - PURPOSE: To assess the microtensile bond strengths of a core composite with two
      different viscosities, MultiCore Flow (F) and Heavy Body (HB) (Ivoclar-Vivadent),
      on dentin and glass-fiber posts with methacrylate resin matrices, in combination
      with three dentin adhesives: Syntac Classic (S), Excite DSC (E), and AdheSE (A)
      (Ivoclar-Vivadent). The omission of an intermediate adhesive coating on silanized
      posts was also examined to see if this resulted in post-core bond strength
      reduction. MATERIALS AND METHODS: Six experimental dentin and 6 experimental post
      groups were formed with different core material viscosity/adhesive combinations.
      In two control post groups, no adhesive was applied on the silanized posts. The
      core material was stratified on deep dentin or on the posts. From the built-up
      teeth and the post-core units, microtensile sticks were obtained. RESULTS: The
      bond strengths measured on dentin were (MPa): S-F 12.7 +/- 6.4; S-HB 18.3 +/-
      7.6; E-F 33.1 +/- 13.7; E-HB 34.1 +/- 10.2; A-F 33.5 +/- 14.8; A-HB 35.5 +/-
      14.4. The post-core strengths were: S-F 9.4 +/- 2.5; S-HB 7.1 +/- 3.8; E-F 8.6 +/
      3.8; E-HB 8.1 +/- 4.4; A-F 8.1 +/- 2.7; A-HB 8.3 +/- 2.4; no adhesive-F 10.4 +/-
      3.6; no adhesive-HB 6.3 +/- 2.7. Significantly higher interfacial strengths were
      achieved on dentin than on posts (p < 0.05). Adhesive type significantly affected
      core-dentin adhesion, with Excite DSC and AdheSE outperforming Syntac Classic (p
      < 0.05). Neither core material viscosity nor adhesive type significantly
      influenced post-core adhesion (p > 0.05). Omission of an intermediate adhesive
      layer had no effect on post-core adhesion (p > 0.05). CONCLUSIONS: Even after
      post surface silanization, the bond established by the composite core material
      with the post remains weaker than that created with coronal dentin.

PMID- 16958290
TI  - The effect of c-factor and flowable resin or fiber use at the interface on
      microtensile bond strength to dentin.
AB  - PURPOSE: As polymerization shrinkage is compensated by flow of the composite,
      several attempts have been performed for relief of the contraction stresses. The
      aim of this in vitro study was to evaluate the effect of flowable composite or
      fiber use under composite restorations on microtensile bond strength of composite
      to dentin in Class I cavities or flat dentin surfaces. MATERIALS AND METHODS:
      Twenty-four sound extracted human first or second mandibular molars were randomly
      assigned to two groups (Class I cavities with a high c-factor or flattened dentin
      surfaces with a low c-factor). The dentin surfaces were treated with adhesive
      resin and restored with resin composite using four different techniques (bulk;
      with flowable composite; with a glass fiber (everStick NET); with a polyethylene
      fiber [Ribbond]). After 24 h storage at 37 degrees C in water, the specimens were
      thermocycled 600 times between 5 and 55 degrees C. Microtensile test specimens
      with a 0.9 x 0.9 (+/- 0.1) mm2 cross-sectional area were produced, and bond
      strength tests were carried out at a crosshead speed of 1 mm/min. Mean bond
      strengths were analyzed using two-way ANOVA and Bonferroni's test at a 95%
      significance level. RESULTS: Flowable composite decreased dentin bond strength in
      cavities with a high c-factor (p < 0.05). The group restored with everStick NET
      showed stable bond strengths regardless of the effect of c-factor. Ribbond THM
      used under composite restorations increased dentin bond strength in cavities with
      a high c-factor (p < 0.05). CONCLUSION: Flowable composite decreased dentin bond
      strength in cavities with a high c-factor; however, using a glass fiber in
      combination with flowable resin, stable bond strengths can be achieved in
      cavities with a high c-factor. Polyethylene fiber in combination with flowable
      resin increases the microtensile bond strength to the dentin floor in cavities
      with a high c-factor.

PMID- 16958291
TI  - A six-month clinical study of a self-etching and an etch-and-rinse adhesive
      applied as recommended and after doubling the number of adhesive coats.
AB  - PURPOSE: In an intra-individual comparison, a 6-month randomized, controlled
      prospective study evaluated the clinical performance of a self-etching and an
      etch-and-rinse adhesive in noncarious cervical lesions applied as recommended and
      after doubling the number of adhesive coats. MATERIALS AND METHODS: Twenty-nine
      patients with at least two pairs of similar sized noncarious cervical lesions
      participated. One hundred sixteen restorations were placed and divided into the
      following groups: OS2: phosphoric acid + One Step Plus applied accordingto
      manufacturer's recommendation (2 coats of adhesive); OS4: phosphoric acid + One
      Step Plus (4 coats of adhesive); TY2: Tyrian SPE + One Step Plus applied
      according to manufacturer's recommendation (2 coats of adhesive); TY4: Tyrian SPE
      + One Step Plus (4 coats of adhesive). The restorations were evaluated at
      baseline and after 6 months according to the modified USPHS criteria. Statistical
      analysis was performed with Friedman repeated measures ANOVA by rank and the
      Wilcoxon sign-ranked test for pairwise significance (alpha = 0.05). RESULTS: One
      hundred eight restorations were evaluated at 6 months. The retention rate of the
      group TY2 was statistically significantly lower than the other groups. Marginal
      discoloration occurred in all groups, being significantly worst in the group TY2.
      CONCLUSION: Tyrian SPE + One Step Plus applied according to manufacturer's
      recommendations did not meet the ADA provisional acceptance criteria for enamel
      dentin bonded restorative materials. The use of four coats of the One Step Plus
      in the self-etching approach can improve its clinical performance.

PMID- 16958292
TI  - Replacing an anterior metal-ceramic restoration with an all-ceramic resin-bonded
      fixed partial denture: a case report.
AB  - Since the first resin-bonded fixed partial denture was described, this adhesive
      technique for splinting mobile teeth has developed into a conservative method for
      replacing missing teeth. Heat-pressed all-ceramic materials have been introduced
      for the fabrication of 3-unit fixed partial dentures in the anterior and premolar
      region. This clinical report describes the replacement of a conventional partial
      coverage metal-ceramic resin-bonded fixed partial denture with an all-ceramic
      resin-bonded fixed partial denture in the anterior maxillary area.

PMID- 16958293
TI  - Utility of the Dipstick Micraltest II in the screening of microalbuminuria of
      diabetes mellitus type 2 and essential hypertension.
AB  - BACKGROUND: In Mexico, diabetes mellitus type 2 and hypertension are leading
      causes of end-stage renal disease. Diagnosis of early renal damage with detection
      of microalbuminuria (microAlbU) is fundamental for treatment and prevention, and
      so avoiding the catastrophes of renal failure. For screening purposes, several
      simplified tests, including dipstick methods, fulfill the accuracy requirements
      for microAlbU detection compared with gold standards; however, no study has
      established the reliability of such tests in our setting. AIM: To evaluate the
      utility of micraltest II as a screening test for microAlbU compared with
      nephelometry in patients with diabetes mellitus type 2 and non-diabetic patients
      with essential hypertension. PATIENTS AND METHODS: Patients with diabetes
      mellitus type 2 as well as patients with essential hypertension of any age, sex
      and time of evolution, attending to three primary health-care units (UMF No. 3,
      92 and 93, Guadalajara, Jalisco) were included. Patients with transitory
      albuminuria, secondary hypertension and serum creatinine > or = 2 mg/dL were
      excluded. Micraltest II was performed in the first morning urine sample, and
      nephelometry was performed in a 24-h urine collection. Diagnostic accuracy of the
      dipstick test was then determined. RESULTS: 245 patients were studied: 71 (29%)
      were diabetics without hypertension, 95 (39%) were diabetics with hypertension,
      and 79 (32%) had only essential hypertension. In diabetic patients, micraltest II
      sensitivity was 83%, specificity 96%, and positive and negative predictive values
      were 95% and 88%, respectively. Correlation between nephelometry and micraltest
      II results was 0.81 (p < 0.001). The best cut-off point for microAlbU was 30.5
      mg/L, and area under the curve (+/- SEM) was 0.91 +/- 0.03 (confidence interval
      95%: 0.85-0.96). In non-diabetic patients with essential hypertension, micraltest
      II sensitivity was 75%, specificity 95%, and positive and negative predictive
      values were 43% and 99%, respectively. Correlation between nephelometry and
      micraltest II results was 0.43 (p < 0.001). The best cut-off point for microAlbU
      was 28.2 mg/L, and area under the curve was 0.85 +/- 0.13 (0.60-1.10).
      CONCLUSION: Micraltest II dispstick is a rapid, valid and reliable method for
      albuminuria screening in patients with diabetes mellitus type 2 and in those non
      diabetic patients with essential hypertension in our setting.

PMID- 16958294
TI  - [Single-layer colonic anastomoses using polyglyconate (Maxon) vs. two-layer
      anastomoses using chromic catgut and silk. Experimental study].
AB  - BACKGROUND: The safety of an intestinal anastomosis is usually measured by its
      complication rate, especially the incidence of anastomotic leakage. A wide
      variety of methods have been described to reestablish intestinal continuity
      including single-layer continuous or two-layer interrupted anastomosis.
      OBJECTIVES: To evaluate if the single-layer continuous anastomosis using
      polygluconate is safer and reliable than two-layer interrupted anastomosis with
      chromic catgut and silk. MATERIAL AND METHODS: A prospective, experimental,
      randomized and comparative analysis was conducted in 20 dogs. They were divided
      in two groups; group 1 underwent two-layer interrupted anastomosis and group 2
      underwent sigle-layer continuous technique. Anastomoses were timed. Both groups
      were under observation. Anastomotic leakage, and other complications were
      evaluated. The animals were sacrified and the anastomosis was taken out together
      with 10 cm of colon on both sides of the anastomosis. Breaking strength,
      histologic evaluation and hydroxyproline determination were performed. RESULTS:
      Ten two-layer anastomosis and ten single-layer anastomosis were performed. A
      median of 25 minutes (range: 20-30 minutes) was required to construct the
      anastomoses in group 1 versus 20 minutes (range: 12-25 minutes) in group 2. All
      animals survived and no leakage was observed. Wound infection ocurred in four
      dogs (20%). Median breaking strength was 230 mm Hg in group 1 and 210 mm Hg in
      group 2. Hydroxyproline concentration was 8.94 mg/g in group 1 (range: 5.33
      16.71) and 9.94 mg/g in group 2 (range: 2.96-21.87). There was no difference
      among groups about the inflammatory response evaluated by pathology. There was no
      statistical significance in any variable evaluated. CONCLUIONS: This study
      demonstrates that a single-layer continuous is similar in terms of safety to the
      two-layer technique, but because of its facility to perform, the single-layer
      technique could be superior.

PMID- 16958295
TI  - Risk factors for anastomotic leakage after preoperative chemoradiation therapy
      and low anterior resection with total mesorectal excision for locally advanced
      rectal cancer.
AB  - BACKGROUND: Risk factors for anastomotic leakage after preoperative
      chemoradiation plus low anterior resection and total mesorectal excision remain
      uncertain. OBJECTIVE: To analyze, the associated risk factors with colorectal
      anastomosis leakage following preoperative chemo-radiation therapy and low
      anterior resection with total mesorectal excision for rectal cancer. MATERIALS
      AND METHODS: Between January 1992 and December 2000, 92 patients with rectal
      cancer were treated with 45 Gy of preoperative radiotherapy and bolus infusion of
      5-FU 450 mg/m2 on days 1-5 and 28-32, six weeks later low anterior resection was
      performed. Univariate analysis was performed as to find the risk factors for
      colorectal anastomotic leakage. RESULTS: There were 48 males and 44 females, mean
      age was 55.8 years. Mean tumor location above the anal verge was 7.4 +/- 2.6 cm.
      Preoperative mean levels of albumin and lymphocytes were 3.8 g/dL and
      1,697/microL, respectively. Mean distal margin was 2.9 +/- 1.4 cm. Multivisceral
      resection was performed in 11 patients (13.8%), 32 patients (35%) had diverting
      stoma. Mean preoperative hemorrhage was 577 +/- 381 mL, and 27 patients (24%)
      received blood transfusion. Ten patients (10.9%) had anastomotic leakage. No
      operative mortality occurred. Risk factors for anastomotic leakage were: gender
      (male) and tumor size > 4 cm. Three patients of the group without colostomy
      required a mean of six days in the unit of intensive care; mean time of hospital
      stay of patients with and without protective colostomy was 12.4 +/- 4.5 days vs.
      18.3 +/- 5.2 days (p = 0.01). CONCLUSION: In male patients with rectal
      adenocarcinoma measuring > 4 cm, treated by preoperative chemoradiotherapy + low
      anterior resection with total mesorectal excision, a diverting stoma should be
      performed to avoid major morbidity due to anastomotic leak.

PMID- 16958296
TI  - [Osteoarticular coccidioidomicosis. Clinical and pathological study of 36 Mexican
      patients].
AB  - Coccidioidomycosis (CM) is primarily a lung disease. Systemic spread occurs in 1%
      of cases and one of its manifestation is osteoarthritis. AIM: To describe the
      clinical and pathological characteristics of 36 patients with osteoarthritis by
      Coccidioides immitis (COA). MATERIAL AND METHODS: The surgical pathology records
      of two medical institutions were reviewed; patients with clinical diagnosis of
      osteoarthritis and definitive histopathological diagnosis of COA were included in
      the study. Results were analyzed by contingence tables (RXC) and chi2 test.
      RESULTS: Twenty six adults (19 men, seven women) and 10 children (seven males,
      three females) were studied. The chi2 analysis demonstrated a predominance of
      disease in men (72.2%, p = 0.008). There was no difference between males and
      females in relation to history of mycotic disease or diagnosis of lung disease
      after the diagnosis of COA. Bone involvement (76% of cases) was more frequent
      that pure joint lesions and the predominant radiological lesion was of lytic
      type. 30.5% of patients (11 cases) had multiple bone lesions and eight of them
      were men with multiple vertebral bone lesions. DISCUSSION: The COA was the only
      manifestation of disease in 83% of the patients. Therefore is important to
      consider this etiology in patients of endemic area. The clinical and radiological
      spectrum of COA is wide and may include a dentigerous and synovial cyst or
      simulates metastatic disease. The recognition of the clinical manifestations of
      COA may contribute to an opportune diagnosis and treatment.

PMID- 16958297
TI  - [Motives for abandoning the healthcare process for precancerous lesions of the
      uterine cervix].
AB  - OBJECTIVE: To determine factors associated with medical care abandon of women
      with CIN. MATERIAL AND METHODS: A nested case-control study in a cohort was done.
      Patients referred to clinical Dysplasia of Gyneco-Obstetrician Services in third
      level Hospitals were considered. CASES: Patients who abandoned medical care.
      CONTROLS: women who attend their medical appointments during follow-up. All
      subjects underwent structured interviews focused on social, clinical and health
      services factors in two different times, applied at the beginning of study and
      the end of follow-up. Clinical records were reviewed to obtain clinical
      information. ANALYSIS: Descriptive and inferential statistical was done. Non
      conditional Logistic Regression analysis was done to obtain adjusted association.
      RESULTS: Abandon cumulative incidence rate was 108/525 = 20.7% (I.C. 95% = 17.2
      24.3); 60.2% happened in diagnosis phase, 17.7% ocured during therapeutic phase
      and 23.1% happened in surveillance phase. We studied 108 cases and 417 controls
      to analysis. Next adjusted risk factors were obtained: Afraid to death (ORa =
      4.2, IC.95% = 1.8-9.5), long appointments (ORa = 6.6, I.C.95% = 3.4-13.0), lack
      of privacity (ORa = 12.5, I.C.95% = 2.6-59.8), reject to treatment (ORa = 40.4,
      I.C.95% = 2.1-785.4), lack of information (ORa = 41.9, I.C.95% =14.2-124.1) and
      other factors. CONCLUSIONS: Patient perception, access and barriers in health
      services were the most important factors associated with medical care abandon.

PMID- 16958298
TI  - [High plasmatic androgen levels in women affected with pregnancy-induced
      hypertension].
AB  - OBJECTIVE: To compare the plasmatic levels of free testosterone (FT), total
      testosterone (TT), and dehydroepiandrosterone sulphate (DHEAs) obtained from
      women with pregnancy-induced hypertension (PIH) and from uncomplicated pregnant
      women in the third trimester of pregnancy. METHODS: FT, TT and DHEAs were
      measured by radioimmunoassay in plasma samples from 30 women with PIH (PIH group)
      defined as mean blood pressure > or = 105 mm Hg, and proteinuria > or = 100 mg/dL
      and < 300 mg/dL, and in 30 women with uncomplicated pregnancies (control group).
      Gestational age at the time of the study in the PIH group was 37 weeks +2 days
      (28+0 - 40+1), and in the control group, 37 weeks +1 day (28+0 - 41+6). The
      plasmatic androgen levels and the perinatal outcome were analysed in both groups.
      RESULTS: There was no difference in the gestational age at birth. In the PIH
      group there were increased number of caesarean sections due to fetal distress
      (PIH group; n = 10, control group; n = 2; p = 0.05), lower birthweight (PIH group
      2549 g [800-3400 g], control group 3242 g [2400-4200 g]; p = 0.02) and increased
      number of neonatal intensive unit care admissions (PIH group; n = 3, control
      group; n = 0). In the PIH group, FT and TT levels were significantly higher than
      controls (mean, SD) (FT PIH group, 5.94 (0.9) pg/mL; FT control group, 0.44 (0.2)
      pg/mL; p = 0.002. TT PIH group, 5.28 (2.4) nmol/L; TT control group, 3.6 (0.6)
      nmol/L; p = 0.02. There was no difference in DHEAs levels between the groups
      (mean, SD) (PIH group, 51.13 (23.7) microg/dL; control group, 70.0 (13.5)
      microg/dL). CONCLUSIONS: In women complicated with PIH there is an increment in
      the plasmatic levels of FT and TT. This might contribute to the clinical findings
      and the adverse perinatal outcome observed in this patients.

PMID- 16958299
TI  - Molecular characterization of alpha-thalassemia in the Mexican population.
AB  - BACKGROUND: alpha-Thalassemia (alpha-Thal) has been poorly characterized at the
      molecular level in Mexico. METHODS: 106 consecutive individuals identified in
      Laboratorios Clinicos de Puebla, with either hypochromia (MCH < 24 pg) and/or
      microcytosis (MCV < 75 fl in women or < 80 fl in man), without iron deficiency,
      with or without anemia were investigated in this study, along a 16 month-period.
      alpha and beta-Thal were looked for, the former were characterized at the
      molecular level. RESULTS: Out of the 106 consecutive cases with hypochromia
      and/or microcytosis and normal levels of protoporphyrin zinc complex, 48 cases
      (45.3%) had thalassemia (37 cases of betaThal and 11 cases of alphaThal), whereas
      in 58 cases (54.7%) a definite diagnosis could not be established. Of the alpha
      Thal cases, 8 were heterozygous and two were homozygous for the -alpha3.7
      deletion, whereas one case was heterozygous for the alpha2Hph allele.
      CONCLUSIONS: Only few of the alpha-Thal alleles tested were found, thus the alpha
      thalassemic mutations, present in the studied population, seem to be rather
      heterogeneous.

PMID- 16958300
TI  - Update in prevention of atherosclerotic heart disease: management of major
      cardiovascular risk factors.
AB  - Cardiovascular disease (CVD) remains as the first cause of death worldwide.
      Scientific community works everyday trying to ameliorate this burden. Only in the
      year 2004 around 2,790 publications about the therapeutic use of antihypertensive
      agents can be found in MEDLINE. Despite this overwhelming effort and information,
      only a relatively short number of manuscripts have a real impact in clinical
      practice. For the busy clinician, it becomes almost impossible to screen and be
      updated with the landmark publications. The purpose of this article is to provide
      concise information related to prevention of CVD. We reviewed publications in the
      past 5 years regarding cardiovascular risk factors with special attention to
      dyslipidemia, hypertension, diabetes, smoking cessation and obesity, discussing
      some new findings and treatments. We also discuss obstructive sleep apnea (OSA)
      as a recently identified cardiovascular risk factor, and provide a general
      overview about its pathophysiology and treatment.

PMID- 16958301
TI  - [Mediastinal tumors].

PMID- 16958302
TI  - [Genetic variations of the tumor suppressor TP53: outstanding and strategies of
      analysis].
AB  - In the modern society, cancer remains an important cause of death. Cancer
      development is a very complex process that involves alterations in genes
      regulating cellular growth. Among these alterations or variations, are included
      point mutations, genetic susceptibility by single nucleotide polymorphisms or
      "SNP" and alteration or loss in tumor suppressor genes functions. The tumor
      suppressor TP53 is one of the most important and studied genes on cancer
      genetics. Therefore, it has been demonstrated that TP53 present mutations in more
      than 50% of all types of human cancer and encodes a multifunctional protein whose
      absence contributes to genomic instability, the accumulation of mutations and
      increased tumor development. The identification of such alterations in cancerous
      cells at level of single nucleotide is very important, because its implication in
      the loss or alteration in the function of this gene, its clinical relevance and
      finally, its association with response to therapy and prognosis. Due to the large
      interesting issue, in this work we are focused only in two of the most common
      genetic variations present in this gene: the point mutations and SNP remarking
      some outstanding molecular characteristics needed for design its analysis.

PMID- 16958303
TI  - [Prediction of effectiveness of electroconvulsive therapy in major depression
      with routinely collected data].
AB  - BACKGROUND: Little is known about the possibility to predict response to
      electroconvulsive therapy (ECT) in patients with major depression. AIM: To create
      an indexforthe prediction ofresponse to ECT in an individual patient. METHOD:
      Fifty-three depressive patients referred for ECT were included. Poor response was
      defined as a decrease in Hamilton Rating Depression Scale less than 50%. With
      multivariable analyses a simple index of independent predictors was constructed.
      RESULTS: Thirty-one patients (58%) showed poor response. The index comprised age
      < 65 years, psychotic depression, refractory to antidepressant medication, and
      personality disorder. It discriminated poor response patients reasonably well
      with an area under the receiver operating characteristic curve of 0.76 (95%
      confidence interval 0.63-0.89). CONCLUSION: Response to ECT may be predicted
      using an index with four patient characteristics. Before implementation, however,
      validation of the index in future patients is mandatory.

PMID- 16958304
TI  - [Differential diagnosis of psychopathy and autism spectrum disorders in adults.
      Empathic deficit as a core symptom].
AB  - BACKGROUND: There is an overlap between the symptoms of psychopathy and autism
      spectrum disorders. AIM: To contribute to an adequate differential diagnosis of
      these disorders. METHOD: We reviewed the literature with the help of PubMed,
      using as key words: 'empathy', 'psychopathy', 'autism', 'aggression' and
      'antisocial' for the period 1980-2004. We also consulted papers listed in the
      bibliographic references for these articles. RESULTS: Empathic deficit is a core
      symptom of both disorders. In psychopathy there are signs of an emotional
      empathic deficit, an inability to feel along with another person (insensitivity).
      Research into autism spectrum disorders points to a cognitive empathic deficit,
      an inability to take the perspective of another person (innocence). The
      antisocial behaviour that can accompany both disorders might be due to the type
      of empathic deficit. In psychopathy the antisocial behavior often involves
      insensitive manipulation and exploitation ofanother person. In autism spectrum
      disorders there is sometimes antisocial behaviour which could be caused partly by
      incorrect evaluation of social situations. In both psychopathy and autism
      spectrum disorders dysfunctioning of the orbitoftontal cortex and the amygdala is
      often mentioned as a possible cause of empathic deficit. CONCLUSION: An accurate
      diagnosis of the type of empathic deficit involved could help to differentiate
      psychopathy from autism spectrum disorders. Good diagnostic tools are not yet
      available.

PMID- 16958305
TI  - [On the way to a treatment law?].
AB  - Under the current Dutch law on special admissions to psychiatric hospitals (Bopz)
      it is possible to detain a patient who is a danger to himself and others. The
      Bopz, however, makes hardly any provisionfor compulsory treatment. Many
      psychiatrists regard this as an inherent shortcoming of the law. Members of the
      public, too, are becoming increasingly concerned by the fact that a seriously ill
      patient can, subject to strict criteria, be detained compulsorily but cannot
      thereafter be compelled to undergo treatment. The legislature has recently made
      some amendments to the Bopz law. The main goals is to widen its scope, making the
      law more flexible with regard to compulsory admission and compulsory treatment.
      In this article we discuss these amendments and new developments and by referring
      to case law we investigate whether these changes increase the possibilitiesfor
      compulsory treatment. We conclude that at the moment they do not.

PMID- 16958306
TI  - [Movement disorders in clinical research].
AB  - Measuring (extrapyramidal) psychotic disorders often is a highly relevant part of
      clinical research into the course and treatment of movement disorders.
      Traditionally these disorders have always been assessed on the basis of a well
      known set of rating scales. The limitations and shortcomings of these scales are
      discussed in the article. It is argued that a new standard instrument needs to be
      developed for the measurement of movement disorders. The SADIMOD can be regarded
      as a good starting point for the development of such an instrument.

PMID- 16958308
TI  - [Danger of social breakdown: compulsory admission, but not treatment? A case
      study].
AB  - Compulsory treatment is permitted (article 38 paragraph 5 Bopz (the Act on
      Special Admissions to Psychiatric Hospitals in the Netherlands)) if this is
      necessary for preventing danger to the patient or other persons and if this
      danger arises from impairment of the patient's mental functioning. Two patients
      are described in which compulsory drug treatment was considered on the grounds
      that the patients were in danger of social breakdown if they remained without
      hope or perspectives in a psychiatric hospital. The court ruled that that danger
      was insufficient to justify compulsory drug treatment. The authors are of the
      opinion that a stay in hospital with no hope or perspectives constitutes social
      breakdown and that the compulsory drug treatment should be applied.

PMID- 16958309
TI  - [Paranoia and symptoms of somatoform disorders in a Nigerian refugee. A case
      study].
AB  - A female Nigerian refugee presented with a combination of paranoia and symptoms
      of somatoform disorders. Her symptoms were interpreted as a cultural expression
      of postpartum depression. The psychotic symptoms subsided when the patient was
      admitted to a psychiatric crisis unit and was given antipsychotics. We describe a
      model that can be used to treat remaining somatoform symptoms with patient
      generated metaphors.

PMID- 16958311
TI  - [Reaction to 'The psychiatrist working in a multidisciplinary team and the
      "Revised Profile of the Psychiatrist'].

PMID- 16958312
TI  - Chromium picolinate intake and risk of type 2 diabetes: an evidence-based review
      by the United States Food and Drug Administration.
AB  - The labeling of both health claims that meet significant scientific agreement
      (SSA) and qualified health claims on conventional foods and dietary supplements
      requires pre-market approval by the US Food and Drug Administration (FDA).
      Approval by the FDA involves, in part, a thorough review of the scientific
      evidence to support an SSA or a qualified health claim. This article discusses
      FDA's evidence-based review of the scientific evidence on the role of chromium
      picolinate supplements in reducing the risk of type 2 diabetes. Based on this
      evidence-based review, FDA issued a letter of enforcement discretion for one
      qualified health claim on chromium picolinate and risk of insulin resistance, a
      surrogate endpoint for type 2 diabetes. The agency concluded that the
      relationship between chromium picolinate intake and insulin resistance is highly
      uncertain.

PMID- 16958313
TI  - Trans fatty acids, insulin resistance, and type 2 diabetes.
AB  - Type 2 diabetes, a growing global health problem, has a complex etiology
      involving many interactions between genetic and environmental factors. Essential
      to the development of the disease is insulin resistance of the peripheral
      tissues. Insulin resistance may be partly modified by the specific types of
      dietary fatty acids. Trans fatty acids (TFAs), created through the transformation
      of polyunsaturated fatty acids from their natural cis form to the trans form, are
      abundant in the Western diet. TFAs take on similar properties as saturated fats,
      and appear to be more atherogenic. High intakes of saturated fats may promote
      insulin resistance. It is therefore reasonable to hypothesize that high intakes
      of TFAs would have similar, or stronger, effects. In this review, all current
      evidence on the topic of TFAs, insulin resistance, and type 2 diabetes is
      summarized and interpreted. Although there is some support from observational and
      experimental studies for the hypothesis that high intakes of TFAs may increase
      the risk for type 2 diabetes, inconsistencies across studies and methodological
      problems make it premature to draw definitive conclusions at this time. More
      experimental research in humans is needed to further address this question.

PMID- 16958314
TI  - What is an adequate dose of oral vitamin B12 in older people with poor vitamin
      B12 status?
AB  - The prevalence of vitamin B12 deficiency increases in the elderly, mainly because
      atrophic gastritis decreases the production of the acid and digestive enzymes
      needed to cleave protein-bound vitamin B12 from the natural chemical form of
      vitamin B12 found in meat, poultry, fish, and dairy foods. Depending on the
      biochemical criterion that is used, 5% to more than 20% of older adults have
      marginal or frank vitamin B12 deficiency. Adults over 50 years of age should meet
      the Recommended Dietary Allowance by consuming vitamin B12 in the crystalline
      form, which does not require gastric acid or enzymes for initial digestion. A
      recent clinical trial suggests that an oral dose of 500 microg/d of crystalline
      vitamin B12 is needed to reverse biochemical signs of vitamin B12 deficiency in
      older adults.

PMID- 16958315
TI  - The regulation of food intake by hypothalamic malonyl-coenzyme A: the MaloA
      hypothesis.
AB  - In animals, food intake and therefore energy balance is regulated by a center in
      the hypothalamus of the brain. Neurons there release appetite-inhibiting
      (anorexigenic) or appetite-stimulating (orexigenic) peptide hormones according to
      whether energy intake exceeds or is less than expenditure, respectively. Recent
      evidence for the "malonyl coenzyme A hypothesis" showed that the level of malonyl
      coenzyme A (MalCoA) in the arcuate nucleus of the hypothalamus determines the
      stimulation or inhibition of food intake. A high level of MalCoA, indicative of
      energy surplus, signals the release of anorexigenic neuropeptides, resulting in
      decreased food intake; a low level of MalCoA, due to an energy deficit such as
      during fasting, signals the release of orexigenic neuropeptides, stimulating food
      intake.

PMID- 16958316
TI  - Do doctors know about their legal responsibilities?

PMID- 16958317
TI  - Recent developments in health law in Belgium.
AB  - After the turbulent years 2002, 2003 and 2004 the Belgian health law seems to
      have reached calmer water. Indeed, after a quiet 2005, 2006 does not seem to have
      much to offer either. However, as will be shown in this article, this may be a
      wrong impression. There is a growing uneasiness with two important pieces of
      legislation that have been approved by Parliament in 2002: the act on euthanasia
      and the act on the rights of patients. This has resulted in debates and
      discussions that may finally lead to new legislation in the coming years.

PMID- 16958318
TI  - Recent developments in German health law.
AB  - Health law provides the regulatory constitution for the medical and healthcare
      system. It covers individual medical treatment as well as public healthcare
      provision and is insofar medical law as well as social security law (statutory
      health insurance law). The medical and health sciences (public health sciences)
      are the main complementary disciplines of health law. This article gives an
      account of some representative developments in both fields which have taken place
      in the last three years.

PMID- 16958319
TI  - Recent developments in health law in Greece.
AB  - This article mainly analyzes the new Code of Ethics which is in place since 2005.

PMID- 16958320
TI  - Recent developments in health law in Poland: new law on the removal, storage and
      transplantation of cells, tissues and organs.
AB  - This article describes the new Law on the removal, storage and transplantation of
      cells, tissues and organs of July 1, 2005, which entered into force on January 1,
      2006.

PMID- 16958321
TI  - Recent developments in Swiss health law.
AB  - This article highlights recent developments in health law in Switzerland. It
      covers statutory developments in health care insurance, sterilisation and genetic
      testing, and cases, one dealing with the reimbursement of medicines and another
      one on the limitation of the number of physicians reimbursed by the compulsory
      scheme of health insurance.

PMID- 16958322
TI  - Recent developments in health law in the Netherlands.
AB  - This article gives a few examples of recent developments in Dutch health law,
      namely equal access to health care, compulsory placement and treatment in a
      psychiatric hospital, and end of life decisions. They are outstanding examples of
      trends in health legislation that require to be followed closely.

PMID- 16958323
TI  - Developments in medical law in the United Kingdom in 2005 and 2006.
AB  - This article highlights and summarises the key developments in medical law in the
      jurisdictions of the United Kingdom in 2005 and to April 2006. Topics are mental
      health and mental capacity, data protection, freedom of information and the
      impact on health data, the Human Tissue Act, genetic research databanks, Human
      Fertilisation and Embryology Act--Review of the legislation, consultations and
      related case law, developments in embryo and embryonic stem cell research,
      clinical trials and human subject research, medical futility, and physician
      assisted dying.

PMID- 16958324
TI  - Informing patients about small risks: A comparative approach.
AB  - This article relates to the question to what extent patients should be informed
      about risks in the context of obtaining consent in case of treatment. To explore
      this issue, a comparative study has been carried out. The legal position taken
      with regard to informing about treatment risks in the Netherlands has been
      compared to that in the UK and Germany.

PMID- 16958325
TI  - CJEC 2006/1, Case C-495/04, Smit-Koolhoven/Staatsecretaris van Financien.

PMID- 16958326
TI  - CJEC 2006/2, case C-124/05, Federatie Nederlandse Vakvereniging (FNV)/Staat der
      Nederlanden.

PMID- 16958327
TI  - CJEC 2006/3, Case C-443/04 and C-444/04, Solleveld & Van den Houtvan
      Eijnsbergen/Staatsecretaris van Financien.

PMID- 16958328
TI  - CJEC 2006/4, Case C-372/04, Watts/Bedford Primary Care Trust.

PMID- 16958329
TI  - ECHR 2006/6 Case of Schmidt v. Germany, 5 January 2006, no. 32352/02 (third
      section).

PMID- 16958330
TI  - ECHR 2006/7 Case of Wilkinson v. The United Kingdom, 28 February 2006, no.
      14659/02 (fourth section).

PMID- 16958331
TI  - ECHR 2006/8 Case of Evans v. The United Kingdom, 7 March 2006, no. 6339/05
      (fourth section).

PMID- 16958332
TI  - ECHR 2006/9 Case of Lerios v. Cyprus, 23 March 2006, no. 68448/01 (first
      section).

PMID- 16958333
TI  - ECHR 2006/10 Case of Csiky v. Hungary, 28 March 2006, no. 32768/03 (second
      section).

PMID- 16958334
TI  - Employee contributions rise in bid to save final salary pension.

PMID- 16958335
TI  - PM calls for empowerment instead of nannying.

PMID- 16958336
TI  - Nicholson: the service insider who puts taxpayers first. Interview by Laura
      Donnelly.

PMID- 16958337
TI  - On the art of delegation.

PMID- 16958338
TI  - Cut and thrust: how Wales went its own way.

PMID- 16958339
TI  - Variations in diagnostic waits.

PMID- 16958340
TI  - Walk the talk.
AB  - Only a tiny percentage of those likely to benefit are offered talking therapies.
      As the cost of incapacity benefit remains high, two talking therapy pilot schemes
      aim to deliver accessible care for those with mild to moderate mental health
      problems. Concerns remain that the pilots are a one-size-fits-all approach to a
      wide spectrum of disorders.

PMID- 16958342
TI  - Healthcare assistants. On a role.

PMID- 16958341
TI  - On mental health.

PMID- 16958343
TI  - Investment tactics improve. But market forces reduce returns for not-for-profits.

PMID- 16958344
TI  - Transparency has its limits. Questions arise about why the transparency-preaching
      Blues association is getting quiet about its members' fiscal results.
AB  - The Blue Cross and Blue Shield Association was touting its plans' devotion to
      transparency last week, unveiling a database offering insight into a variety of
      healthcare trends. But some are doubting the Blues' sincerity, given the
      association's decision to withhold aggregate plan financial results. "It seems
      very inconsistent with their new emphasis on transparency and empowering people
      with information," says Bruce McPherson, left.

PMID- 16958345
TI  - Easing the impact. CMS blunts effect of new inpatient PPS.

PMID- 16958346
TI  - Ripe for change: study. Commonwealth Fund develops healthcare 'scorecard'.

PMID- 16958347
TI  - Not-for-profits prosper, Moody's annual review shows more upgrades, profit.

PMID- 16958348
TI  - Charity-care wrangling. Ohio, Wis. unveil separate payment strategies.

PMID- 16958349
TI  - Rural areas cool to HCA. Town opposes ending inpatient services at hospital.

PMID- 16958350
TI  - Bad medicine. Big Pharma's cash injections lead to poor ethical outcomes.

PMID- 16958351
TI  - The limits of technology. Far from a panacea, IT is merely a tool for solving
      problems.

PMID- 16958352
TI  - HIPPA, 10 years after.

PMID- 16958353
TI  - Help wanted. Benefits include an idyllic rural setting, a friendly community and
      some assistance paying off those hefty medical school loans.

PMID- 16958354
TI  - 30 events/innovations from the past. From AHERF to unionization, 30 events and
      innovations that have a powerful impact on healthcare.

PMID- 16958355
TI  - 30 people from the past. From Altman to Waxman, 30 people who have had a powerful
      impact on healthcare.

PMID- 16958356
TI  - 30 trends/innovations to watch. From biologics to universal coverage, 30 trends
      and innovations that will have a powerful impact on healthcare.

PMID- 16958357
TI  - 30 people for the future. From Blagojevich to Zerhouni, 30 people who could have
      a powerful impact on healthcare.

PMID- 16958358
TI  - Why is this Indiana doctor sitting in jail?

PMID- 16958359
TI  - Physician report cards: help, ho-hum or horror?

PMID- 16958360
TI  - Volunteers cut Rx red tape.

PMID- 16958361
TI  - The Catch-22 in EHRs.

PMID- 16958362
TI  - The wrong message.

PMID- 16958363
TI  - Does your front-desk staff draw patients in--or turn them off?

PMID- 16958364
TI  - Adding ancillaries. Dispensing drugs.

PMID- 16958365
TI  - Avian flu. Is your practice ready?

PMID- 16958366
TI  - Preparing patients for avian flu.

PMID- 16958367
TI  - Is it ever okay to date a patient?

PMID- 16958368
TI  - For-profit sales rising: report. Investor-owned acquisitions reached 76% in 2005.

PMID- 16958370
TI  - Ochsner, Tenet deal. Clinic to buy three N.O. hospitals.

PMID- 16958369
TI  - Life-altering decisions. Katrina-related murder arrests for three New Orleans
      healthcare workers could have major implications for industry.
AB  - The arrests of three New Orleans hospital workers for alleged second degree
      murder of four patients after Hurricane Katrina put into bold relief the
      unexpectedly bad ways disaster management can turn out. But the lessons of
      Katrina aided many. When faced with Hurricane Rita three weeks after Katrina,
      Karen Sexton, left, modified her hospital's evacution plan to get out the sickest
      patients on first.

PMID- 16958372
TI  - Investors eye HCA. Stock rises after failed attempt to go private.

PMID- 16958371
TI  - Medication errors persist: IOM. Report highlights steps to reduce severity,
      frequency.

PMID- 16958373
TI  - CIA backs health IT developer. Agency's venture capital arm invests in software
      firm.

PMID- 16958374
TI  - Tufts leaves Destiny behind. Insurer cuts ties with medical savings account
      provider.

PMID- 16958375
TI  - Tennessee tensions. HCA fights for CON in booming Nashville suburb.

PMID- 16958376
TI  - HRDI loses 10 members.

PMID- 16958377
TI  - Big shoes to fill for big shoulders. With exodus of CEOs, will Chicago's
      influence wane?

PMID- 16958378
TI  - One delay we can live with. Patient-safety law's slow rollout just another sign
      of its inefficacy.

PMID- 16958379
TI  - A gap in the pharmacy. No effort is being made to address leadership void.

PMID- 16958380
TI  - Healthcare's place in the sun. Execs, GAO find sandy beaches, salty Medicaid
      funding in U.S. territories.

PMID- 16958381
TI  - Tracking ties to infection. As rates of hospital-acquired infections have risen,
      adding billions in costs, experts view a wide range of remedies.

PMID- 16958384
TI  - From there to here: a personal viewpoint after three decades of neuropathy
      research.
AB  - Currently there is unprecedented interest in research, writing, and clinical
      experience related to lower extremity peripheral nerve surgery. Its time is here,
      now. Application of the concepts for diagnosis and treatment of nerve
      compression, painful neuroma, and neuropathy has been a direct extension from the
      upper extremity to the lower extremity. By the end of 2005, there were more than
      a dozen studies demonstrating that the basic neuropathy causes metabolic changes
      that render the peripheral nerve susceptible to chronic nerve compressions. My
      hypothesis continues to assert that surgical decompression of known sites of
      compression can relieve symptoms of neuropathy that are caused by superimposed
      nerve compressions.

PMID- 16958385
TI  - Conservative treatment of peripheral neuropathy and neuropathic pain.
AB  - There are many types of peripheral nerve disorders that lead to peripheral
      neuropathy. Symptoms associated with peripheral neuropathy lack consistent, easy
      to treat qualities, and provide a constant challenge for physicians who encounter
      the sequelae of neuropathy. This review discusses medications, nutritional
      supplements, and topical and physical modalities that are effective in treating
      neuropathy associated with diabetes.

PMID- 16958386
TI  - Electromyography and nerve conduction studies of the lower extremity: uses and
      limitations.
AB  - Electrodiagnostic testing (EDX), the combination of electromyography and nerve
      conduction studies, is a useful extension of the physical exam. In the proper
      clinical context, it can help distinguish between the various nerve processes
      that may contribute to foot pain. This article discusses those processes, their
      clinical presentation, and the relative usefulness of EDX for each.

PMID- 16958387
TI  - Quantitative sensory testing.
AB  - The diagnosis and treatment of peripheral neuropathy from any cause has come to
      the forefront of the research community in the past few years. Both past and new
      diagnostic and treatment options have been and are being studied to better
      understand and properly treat this debilitating and sometimes devastating
      disease. One such advancement is the clinical use of quantitative sensory
      testing. To identify etiology of the neuropathy early, the testing instrument
      would need to identify changes throughout the course of the disease, have a
      normative database, and show a clear distinction between the absence or presence
      of disease. The pressure specified sensory device (PSSD) was developed in 1992 to
      painlessly investigate the cutaneous pressure thresholds quantitatively and
      accurately.

PMID- 16958388
TI  - Prognostic ability of a good outcome to carpal tunnel release for decompression
      surgery in the lower extremity.
AB  - For years, patients who were treated successfully with carpal tunnel release were
      told there was nothing that could be done about their lower extremity symptoms.
      Now that lower extremity nerve decompression has been accepted as an option to
      treat appropriate patients, the authors looked for correlations between a
      successful outcome with carpal tunnel syndrome and its predictive value of
      success for lower extremity nerve decompression. Data from a recent study
      demonstrate that a good result from upper extremity peripheral nerve surgery
      predicts the outcome for lower extremity peripheral nerve surgery in 88% of
      patients, and is, therefore, information valuable for prognosis and clinical
      decision-making.

PMID- 16958389
TI  - Intermetatarsal compression neuritis.
AB  - Intermetatarsal compression neuritis can be a disabling condition. Individuals
      who don't respond well to initial treatments are left with persistent pain and
      frustration. The conservative approach to the treatment of neuromas includes shoe
      modifications, padding, orthotics, cortisone injections, and serial alcohol
      sclerosing injections. When a person has failed conservative treatment for a
      forefoot neuroma, surgery can be considered to alleviate pain and treat the
      condition. This article describes several different surgical approaches such as
      neurectomy, carbon dioxide laser, and neurolysis. Results to date show that
      decompression is similar to neurectomy surgery, if not more successful.

PMID- 16958390
TI  - Endoscopic nerve decompression.
AB  - Endoscopic decompression for forefoot nerve entrapments is discussed in this
      article from not only the perspective of preoperative indications, intraoperative
      technique, and postoperative management, but with reference to the changing
      paradigm for management of this condition. Surgical results are discussed and
      compared with other published reports. Complications of the surgical technique
      are also discussed, which will give the operating surgeon a frame of reference
      when comparing decompression procedures to those techniques involving nerve
      resection. There is also a valuable discussion of current methods of diagnosis
      that may help the practitioner improve patient outcomes.

PMID- 16958391
TI  - Tarsal tunnel syndrome: a compression neuropathy involving four distinct tunnels.
AB  - Tarsal tunnel syndrome is a complex and often under-diagnosed or misdiagnosed
      condition that affects the foot and ankle. It is a compression neuropathy of the
      posterior tibial nerve as it passes in the anatomic tarsal tunnel in the medial
      ankle under flexor retinaculum. This article reviews diagnosis, conservative
      treatment, and surgical outcomes, which have dramatically improved with more
      comprehensive release of the foot nerves in addition to the tibial nerve.
      Internal neurolysis facilitates a second level of nerve decompression in needed
      cases. Physical therapy protocols have made it possible for patients to return to
      ambulation with limited long-term down time.

PMID- 16958392
TI  - Anterior tarsal tunnel syndrome.
AB  - Compression of the deep peroneal nerve is commonly referred to as anterior tarsal
      tunnel syndrome. Although rare, this syndrome remains poorly diagnosed. The
      syndrome is characterized by pain, weakness, and sensory changes of the foot and
      ankle. Non-operative measures should be attempted to reduce or remove the
      external compression along the anterior aspect of the foot and ankle. Other
      options include shoe modifications, cortisone injections,and physical therapy. If
      conservative management fails to relieve the symptoms, surgical decompression of
      the entrapped nerve can be performed. The deep peroneal nerve is released from
      compressive forces in the entrapment site. This can be performed at the more
      proximal level at the extensor retinaculum or more distally at the level of the
      tarsal metatarsal site.

PMID- 16958393
TI  - Surgical decompression for painful diabetic peripheral nerve compression and
      neuropathy: a comprehensive approach to a potential surgical problem.
AB  - Diabetic nerve decompression is not for every patient. There is a definite
      learning curve to the surgery and recovery process and the surgeon must be
      available to the patient for concerns during the recovery period. The surgery
      itself is not very complex and can be mastered over time. Pain relief and return
      to activity results have been excellent and overall, the surgical decompression
      patients fair better in regard to ulcer formation and amputation risk than those
      without decompression. It is essential to select patients carefully and to make
      sure that the testing and examination findings discussed in the article are
      present before surgery.

PMID- 16958394
TI  - Chemotherapy-induced neuropathy.
AB  - Increasingly, surgeons are becoming aware of the successful treatment of
      symptomatic peripheral neuropathy by surgical decompression of peripheral nerves.
      Armed with the knowledge that patients can have underlying neuropathy with
      overlying anatomic compressions, surgeons have affected improvement in diabetes
      induced neuropathy, neuropathy of unknown etiology, and chemotherapy-induced
      neuropathy. This article details the most well-known culprits in chemotherapy
      induced neuropathy and discusses the putative mechanisms of action, medical
      management, and surgical data.

PMID- 16958395
TI  - Physical therapy following peripheral nerve surgeries.
AB  - Post-operative care of the surgical patient significantly contributes to the
      success of the surgical procedure. Post-operative physical therapy is directed at
      reducing pain and inflammation, preventing or minimizing scar tissue, and
      returning the patient to full function. An individualized and well-planned
      therapeutic exercise program is an integral part of the post-operative care.
      Manual therapy techniques are utilized to break up scar tissue and reduce joint
      stiffness. Pain and inflammation can be addressed by modalities such as
      ultrasound, laser, and electrical stimulation in addition to cryotherapy.

PMID- 16958396
TI  - Preliminary examination to determine the suitable contrast material injection
      protocol for CT angiography of the pelvis and lower extremities with a
      multidetector row helical scanner.
AB  - PURPOSE: The aim of this study was to determine the best of three protocols for
      the depiction of arteries in the pelvis and lower extremities by computed
      tomographic angiography (CTA) with a multidetector row helical scanner. MATERIALS
      AND METHODS: CTA was performed in five asymptomatic volunteers using a four
      channel multidetector row helical scanner. Low-osmolar iodinated contrast
      material was injected at the flow rate of 3 ml/s using three protocols: 100 ml of
      300 mg I/ml, 150 ml of 300 mg I/ml, and 100 ml of 350 mg I/ml. The CT number of
      opacified blood was measured at six levels. Three doctors independently assessed
      the degree of depiction of arteries on CTA images without knowing the protocol
      using a 3-point scale. RESULTS: CT numbers at the level of the popliteal artery
      on the protocol of 150 ml of 300 mg I/ml were significantly greater than the
      others. The mean score for the depiction of trifurcation on the protocol of 150
      ml of 300 mg I/ml was significantly greater than those in the others. CONCLUSION:
      The protocol of 150 ml of 300 mg I/ml was the best for depicting arteries in the
      pelvis and lower extremities by CTA.

PMID- 16958397
TI  - Self-expandable metallic stent placement for patients with inoperable esophageal
      carcinoma: investigation of the influence of prior radiotherapy and chemotherapy.
AB  - PURPOSE: The aim of this study was to evaluate the efficacy and complications of
      self-expandable metallic stent placement for patients with inoperable esophageal
      carcinoma after radiotherapy and/or chemotherapy. MATERIALS AND METHODS: We
      obtained data from 19 patients with advanced or recurrent esophageal carcinoma
      between 1996 and 2000. In all patients, a self-expandable metallic stent was
      placed under fluoroscopic guidance. Dysphagia before and after stent placement
      was graded. Complications after stent placement were also evaluated. Data were
      compared between patients with and without prior radiotherapy and/or
      chemotherapy. RESULTS: The procedure was technically successful in all but one
      patient. The dysphagia grade improved in all patients. No life-threatening
      complications occurred. The other major complications such as mediastinitis
      occurred in two patients, and pneumonia and funnel phenomenon occurred in one
      patient each. These patients had a history of radiotherapy and/or chemotherapy
      prior to stent placement. Eight of the twelve patients with prior radiotherapy
      and/or chemotherapy compared with one of seven patients without prior therapy had
      persistent chest pain, which was a statistically significant difference (P <
      0.05). CONCLUSION: Placement of self-expandable metallic stents was effective for
      patients with advanced or recurrent esophageal carcinoma. However, prior
      irradiation and/or chemotherapy increased the risk of persistent chest pain after
      stent placement.

PMID- 16958398
TI  - Change of diffusion anisotropy in patients with acute cerebral infarction using
      statistical parametric analysis.
AB  - PURPOSE: We conducted statistical parametric comparison of fractional anisotropy
      (FA) images and quantified FA values to determine whether significant change
      occurs in the ischemic region. MATERIALS AND METHODS: The subjects were 20
      patients seen within 24 h after onset of ischemia. For statistical comparison of
      FA images, a sample FA image was coordinated by the Talairach template, and each
      FA map was normalized. Statistical comparison was conducted using SPM99. Regions
      of interest were set in the same region on apparent diffusion coefficient (ADC)
      and FA maps, the region being consistent with the hyperintense region on
      diffusion-weighted images (DWIs). The contralateral region was also measured to
      obtain asymmetry ratios of ADC and FA. RESULTS: Regions with areas of statistical
      significance on FA images were found only in the white matter of three patients,
      although the regions were smaller than hyperintense regions on DWIs. The mean ADC
      and FA ratios were 0.64 +/- 0.16 and 0.93 +/- 0.09, respectively, and the degree
      of FA change was less than that of the ADC change. Significant change in
      diffusion anisotropy was limited to the severely infarcted core of the white
      matter. CONCLUSION: We believe statistical comparison of FA maps to be useful for
      detecting different regions of diffusion anisotropy.

PMID- 16958399
TI  - Proposal of blood volume-corrected model for quantification of regional cerebral
      blood flow with H2 15O-PET and its application to AVF.
AB  - PURPOSE: It is generally assumed that vascular tracer activity is negligible in
      the quantification of regional cerebral blood flow (rCBF) with H2 15O and
      positron emission tomography (PET) under normal conditions. We attempted to
      surpass the assumption of abnormal vascular conditions where the vascular tracer
      activity is significant by introducing the vascular component into the model.
      MATERIALS AND METHODS: H2 15O-dynamic and C15O PET scans were performed in an
      arteriovenous fistula (AVF) patient. Time-activity curves of regions of interest
      (ROIs) were analyzed with nonlinear least-square approximation to estimate the
      rCBF and fractional arterial blood volume (v(a)) simultaneously with the proposed
      model and the standard model. RESULTS: The proposed model curve showed a fit to
      the time-activity curve of H2 15O at an ROI containing an enlarged vascular space
      induced by the AVF. The relation between the estimated v(a) and CBV obtained with
      C15O-PET revealed that the ratio of v(a) to CBV was approximately 0.23. The
      estimated rCBF with the proposed model in nonlesion ROIs corresponded to those of
      the standard model, with the estimated V(d) 0.94 ml/ml. CONCLUSION: The results
      supported the hypothesis that the blood volume-corrected model is applicable to
      the quantification of rCBF in a region with abnormal vascular structure.
      Furthermore, one of the advantages of the model is the feasibility of
      simultaneous estimation of the rCBF and arterial blood volume with dynamic-H2 15O
      PET scans.

PMID- 16958400
TI  - Monte Carlo dose calculations for a 6-MV photon beam in a thorax phantom.
AB  - PURPOSE: In this study we evaluated the accuracy of the Monte Carlo (MC) and
      effective path length (EPL) methods for dose calculations in the inhomogeneous
      thorax phantom. MATERIALS AND METHODS: The Philips SL 75/5 linear accelerator
      head was modeled using the MCNP4C Monte Carlo code. An anatomic inhomogeneous
      thorax phantom was irradiated with a 6-MV photon beam, and the doses along points
      of the central axis of the beam were measured by a small ionization chamber. The
      central axis relative dose was calculated by the MCNP4C code and the EPL method
      in a conventional treatment planning system. The results of calculations and
      measurements were compared. RESULTS: For all measured points on the thorax
      phantom the results of the MC method were in agreement with the actual
      measurement (local difference was less than 2%). For the EPL method, the amount
      of error was dependent on the field size and the point location in the phantom.
      The maximum error was +19.5 and +26.8 for field sizes of 10 x 10 and 5 x 5 cm2
      for lateral irradiation. CONCLUSION: Our study showed large, unacceptable errors
      for EPL calculations in the lung for both field sizes. The accuracy of the MC
      method was better than the recommended value of 3%. Thus, application of this
      method is strongly recommended for lung dose calculations, especially for small
      field sizes.

PMID- 16958401
TI  - Retrospective analysis: concurrent chemoradiotherapy using protracted continuous
      infusion of low-dose cisplatin and 5-fluorouracil for T2N0 glottic cancer.
AB  - PURPOSE: Treatment with conventional radiotherapy alone for local control of T2
      glottic cancer (T2GC) is insufficient. To improve local control of T2GC, we have
      simultaneously administered continuous intravenous infusions of low-dose
      cisplatin and 5-fluorouracil (5-FU) in combination with irradiation. MATERIALS
      AND METHODS: We performed this combination therapy in a total of 11 consecutive
      patients with previously untreated invasive squamous cell carcinoma (T2GC).
      Cisplatin was administered at 4 mg/m2/day and 5-FU at 200 mg/m2/day for 120 h,
      except during weekends, beginning on the day irradiation with a once-daily
      fraction at 2 Gy was started. RESULTS: An initial local control rate of the
      primary tumor was achieved in 10 of the 11 patients (91%), and ultimate laryngeal
      preservation by cordectomy was achieved in all cases. Regarding adverse
      reactions, grade 3 or 4 hemotoxicity did not develop in any of the patients.
      Grade 3 laryngitis was observed in four patients (36%), but none of these
      patients required interruption of treatment owing to acute laryngeal reactions.
      CONCLUSION: Instead of radiotherapy alone, this combination chemoradiotherapy is
      suggested with the possibility of improving local control of T2GCs.

PMID- 16958402
TI  - Pseudoaneurysm embolization and vasopressin infusion for lower gastrointestinal
      bleeding due to recurrence of urinary bladder carcinoma.
AB  - We report a case that was successfully treated for massive lower gastrointestinal
      (LGI) bleeding due to a recurrent urinary bladder carcinoma. Treatment consisted
      of combination therapy including embolization of an inferior gluteal artery (IGA)
      pseudoaneurysm and low-dose arterial vasopressin infusion via a sigmoid artery
      (SA). A 57-year-old man presented with life-threatening sudden, massive LGI
      bleeding due to an obturator lymph node (LN) metastasis from a urinary bladder
      carcinoma. Computed tomography showed that the LN recurrence had invaded all the
      way to the sigmoid colon, and there was a pseudoaneurysm with extravasation
      inside the recurrence. An angiogram revealed a left IGA pseudoaneurysm. We
      therefore excluded the pseudoaneurysm by embolization with microcoils. Following
      this treatment the bleeding decreased, but intermittent LGI bleeding continued.
      Endoscopic examination showed the tumor with a huge ulcer inside the colonic
      lumen, and continuous oozing was confirmed. A second angiogram showed no
      recurrence of the IGA pseudoaneurysm and no apparent findings of bleeding. Then a
      3F microcatheter was placed in the SA selectively using a coaxial catheter
      system, and vasopressin was infused at a rate 0.05 U/min for 12 h. Bleeding
      completely ceased 2 days later. There were no signs of ischemic gastrointestinal
      complications. Massive LGI bleeding has not recurred in 5 months.

PMID- 16958403
TI  - Long-term local control of recurrent adenoid cystic carcinoma in the parotid
      gland with radiotherapy and intraarterial infusion chemotherapy.
AB  - We report a case of postoperative recurrence of adenoid cystic carcinoma in the
      left parotid gland treated with radiotherapy and arterial infusion chemotherapy.
      A 52-year-old woman had a history of surgical resection for an adenoid cystic
      carcinoma arising from the left parotid gland 25 years before. Despite two
      reoperations for local recurrence after the initial surgery, she had a third
      local recurrence in the remnant of the left parotid gland. The patient was
      treated with a concurrent combination of radiotherapy (60 Gy/30F) and
      intraarterial infusion chemotherapy with carboplatin (750 mg/30 days) from which
      she obtained a complete response. The patient has remained free of local
      progression 54 months after treatment. Radiotherapy and arterial infusion
      chemotherapy is effective treatment for local recurrence of adenoid cystic
      carcinoma in the head and neck.

PMID- 16958404
TI  - Recurrent thymoma: radiological (CT and FDG-PET) and histological (WHO criteria)
      features.
AB  - A 66-year-old man, who had undergone surgical resection of a primary noninvasive
      thymoma (type B1) in the right anterolateral mediastinum 6 years before,
      underwent follow-up computed tomography (CT) scanning. The CT scan revealed a few
      nodules located at the posterior portion of the right thoracic base and just
      behind the right upper anterior chest wall. Subsequent fluorodeoxyglucose
      positron emission tomography (FDG-PET) scans showed multiple foci with high
      [standard uptake value (SUV) 4.3] and low (SUV 2.6) FDG uptake in the right lower
      posterior area and right upper anterior area of the chest, respectively. The
      fusion image of the CT and FDG-PET scans demonstrated that the areas of the
      increased FDG uptake corresponded to those of the nodules on the CT scan. All of
      the nodules were successfully removed surgically, and the histological features
      of the nodules indicated that they were type B1 or types B1 plus B2. We regarded
      the nodule located just behind the right upper anterior chest wall as a type B1
      thymoma, whereas those in the posterior area of the right thoracic base as
      combined thymomas of types B1 plus B2. Our limited experience suggests that the
      degree of FDG uptake is a reflection of the subtype according to the World Health
      Organization (WHO) criteria. Furthermore, we showed the role of FDG-PET in the
      accurate assessment of recurrent thymoma and its therapeutic strategy.

PMID- 16958405
TI  - Pulmonary spread of laryngeal papillomatosis: radiological findings.
AB  - Laryngeal papillomatosis is a rare benign disease seen in children and young
      adults. The spread of laryngeal papillomas throughout the respiratory tract
      occurs rarely; and involvement of the distal bronchi, bronchioles, and lung
      parenchyma is very rare. We report a case of pulmonary spread of laryngeal
      papillomatosis in a 34-year-old man, focusing on the radiological evidence. Chest
      radiographs showed pulmonary nodules, but computed tomography scans more clearly
      demonstrated multiple small nodules showing cavitations and distributed
      centrilobularly. Pulmonary nodules and cavitations progressed gradually through
      the 6-year follow-up. The combination of clinical and characteristic radiological
      features suggests a diagnosis of pulmonary spread of laryngeal papillomatosis.

PMID- 16958406
TI  - Functional neuroimaging in Alzheimer's disease.

PMID- 16958407
TI  - Principles and techniques of transcatheter embolotherapy for peripheral vascular
      lesions.
AB  - Transcatheter embolotherapy (TCE), a common procedure for interventional
      radiologists, comprises transcatheter delivery of embolic agents into target
      vessels in order to eliminate lesions or lesion-associated symptoms. Good
      knowledge of delivery catheters and embolic agents is essential to optimize
      embolization techniques and to obtain the desired therapeutic outcomes. In this
      review, we describe the principles and techniques of TCE for peripheral arterial
      and venous lesions featuring visceral aneurysms, peripheral and pulmonary
      arteriovenous malformations (AVMs), and varicoceles.

PMID- 16958408
TI  - Balloon-occluded retrograde transvenous obliteration for portal hypertension.

PMID- 16958409
TI  - Factors contributing to blood-brain barrier disruption following intracarotid
      injection of nonionic iodinated contrast medium for cerebral angiography:
      experimental study in rabbits.
AB  - PURPOSE: This study was performed to investigate the role of injection methods
      and conditions under a fixed dose of radiographic contrast medium (CM) in respect
      to promoting blood-brain barrier (BBB) disruption. MATERIALS AND METHODS: A total
      of 44 white rabbits (average body weight 2.7 +/- 0.4 kg) were used, and their
      carotid injection was performed with nonionic CM. The variables assessed for the
      carotid injections included the following: iodine content (300 or 150 mg I/ml),
      liquid temperature (37 degrees or 24 degrees C), and the injection time duration
      (1 or 30 s). The rabbits were divided into five groups. To evaluate BBB
      disruption, pre- and post-contrast-enhanced magnetic resonance (MR) studies were
      performed. RESULTS: Abnormal enhancement of the brain parenchyma in MRI was noted
      in only one group, which consisted of high-iodine concentration CM injected at a
      low temperature over a short injection interval. Statistically significant
      increased values for the percentage of relative enhancement (RE%) were
      demonstrated (P < 0.05) in comparison with the saline-injected control group.
      CONCLUSION: This result suggests variables that may need to be carefully
      considered to prevent BBB injury induced by nonionic CM for cerebral angiography,
      especially in the setting of a neurointerventional procedure.

PMID- 16958410
TI  - High-resolution MRI using a microscopy coil for the diagnosis of recurrent
      lateral patellar dislocation.
AB  - PURPOSE: Magnetic resonance imaging (MRI) has been commonly used for the
      preoperative evaluation of recurrent lateral patellar dislocation (RLPD). The
      purpose of this study was to determine the usefulness of high-resolution MRI (HR
      MRI) with a microscopy coil for diagnosing RLPD. MATERIALS AND METHODS: The study
      group consisted of 15 patients with clinically diagnosed RLPD and 10 normal
      volunteers. All studies were performed on a 1.5-T MR system. First, conventional
      MRIs of the whole knee joint were obtained using the knee coil. Then HR-MRI scans
      using a microscopy coil in the medial aspect of the patella were obtained at the
      level of the superior pole of the patella, targeting the medial patellofemoral
      ligament (MPFL). The acquired HR-MRIs with RLPD were reviewed concerning the MPFL
      injury and the patellar injury. RESULTS: The MPFL was distinguished as a separate
      ligament, and the layer structure of the patellar cartilage was visualized
      clearly in all volunteers. The MPFL injury was visualized in 12 cases (87%); it
      included discontinuity, thickening, and loosening. The patellar injury was
      visualized in 11 cases (73%), which included dissecans of the medial margin and
      cartilage injuries. CONCLUSION: HR-MRI with a microscopy coil provides precise
      information of the MPFL and patellar cartilage injury for the diagnosis of RLPD.

PMID- 16958411
TI  - Cerebral glucose metabolism change in patients with complex regional pain
      syndrome: a PET study.
AB  - PURPOSE: The aim of this study was to examine abnormalities of the central
      nervous system in patients with chronic pain who were diagnosed with complex
      regional pain syndrome (CRPS). MATERIALS AND METHODS: Brain activity was assessed
      using (18)F-fluorodeoxyglucose positron emission tomography. The data collected
      from 18 patients were compared with data obtained from 13 normal age-matched
      controls. RESULTS: Our results showed that glucose metabolism was bilaterally
      increased in the secondary somatosensory cortex, mid-anterior cingulated cortex
      (ACC) or posterior cingulated cortex (PCC) (or both), parietal cortex, posterior
      parietal cortex (PPC), and cerebellum as well as in the right posterior insula
      and right thalamus in our patients. In contrast, glucose metabolism was reduced
      contralaterally in the dorsal prefrontal cortex and primary motor cortex. Glucose
      metabolism was bilaterally elevated in the mid-ACC/PCC and the PPC, which
      correlated with pain duration. CONCLUSION: These data suggested that glucose
      metabolism in the brains of patients with CRPS changes dramatically at each
      location. In particular, glucose metabolism was increased in the areas concerned
      with somatosensory perception, possibly due to continuous painful stimulation.

PMID- 16958412
TI  - White matter changes on magnetic resonance imaging following whole-brain
      radiotherapy for brain metastases.
AB  - PURPOSE: The purpose of this study was to evaluate white matter (WM)
      abnormalities induced by WBRT. MATERIALS AND METHODS: Twenty-four patients (11
      men and 13 women; age range 38-74 years, median 60 years) who survived for more
      than 1 year after completion of WBRT (radiation dose range 30-40 Gy, median 35
      Gy) at our institution between January 2000 and June 2003 were followed up with
      magnetic resonance (MR) scans for 11-51 months (median 19 months). We evaluated
      WM changes attributable to WBRT as grade 0-6 and assessed possible contributing
      factors by statistical analysis. RESULTS: WM changes were found in 20 patients:
      Eight were assessed as grade 2, three as grade 3, and nine as grade 5. In total,
      12 patients developed grade 3 or higher WM changes. Age (<60 vs > or =60 years),
      sex, radiation dose (< or =35 vs >35 Gy), chemotherapy (with CDDP vs without
      CDDP), biologically effective dose (< or =120 vs >120 Gy1), and head width (<16.3
      vs > or =16.3 cm) were found not to be relevant to the incidence or severity of
      the WM changes. CONCLUSION: Long-term survivors who have under-gone WBRT may have
      a higher incidence of WM abnormalities.

PMID- 16958413
TI  - Evaluation of usefulness of color digital summation radiography for solitary
      pulmonary nodules on chest radiographs.
AB  - PURPOSE: The aim of this study was to evaluate the usefulness of novel color
      digital summation radiography (CDSR) for detecting solitary pulmonary nodules on
      chest radiographs by observers with different levels of experience. MATERIALS AND
      METHODS: A total of 30 healthy controls and 30 patients with newly detected
      solitary pulmonary nodules were evaluated. Six radiologists and five residents
      evaluated three image sets: set A, current and prior radiographs only; set B, set
      A with temporal subtraction images; and set C, set A with CDSR. The observers
      were asked to rate each image set using a continuous rating scale. In addition,
      the reading time required for each set was recorded. RESULTS: The radiologists
      showed no significant differences in the mean A(z) value between set A, set B,
      and set C. However, the residents showed significant differences between set A
      and set B and between set A and set C. In addition, for set B and set C, the mean
      reading time per case of all readers was significantly shorter than that for set
      A. CONCLUSION: The detection capability of observers with little experience is
      comparable to that of experienced observers when reading radiographs with
      temporal subtraction images or with CDSR. The usefulness of CDSR is comparable to
      that of temporal subtraction.

PMID- 16958414
TI  - Small bowel perforation resulting from blunt abdominal trauma: interval change of
      radiological characteristics.
AB  - PURPOSE: We analyzed radiography and computed tomography (CT) findings of small
      bowel perforation due to blunt trauma to identify the keys to diagnosis.
      MATERIALS AND METHODS: Twelve patients with surgically proven small bowel
      perforation were retrospectively studied. All patients underwent radiography and
      CT, and five underwent presurgical follow-up CT. Radiological findings were
      evaluated and correlated to the elapsed time from the onset of the trauma
      retrospectively. RESULTS: Radiography demonstrated free air in only 8% (1/12) and
      25% (3/12) at the initial and follow-up examinations, respectively. In contrast,
      the initial and follow-up CT scans detected extraluminal air in 58% (7/12) and
      92% (11/12), respectively. Mesenteric fat obliteration was seen in 58% (7/12) and
      75% (9/12) at initial and follow-up CT, respectively. The incidence of both
      extraluminal air and mesenteric fat obliteration on CT increased as time elapsed,
      particularly after 8 h. High-density ascites was seen in 75% at initial CT,
      including two patients without extraluminal air, but was observed in all but one
      patient at follow-up CT. CONCLUSION: The chance of detecting extraluminal air
      increases as time elapses. High-density ascites may be seen without extraluminal
      air and might be an indirect or precedent sign of small bowel perforation.
      Radiologists need to be familiar with these radiological features.

PMID- 16958415
TI  - Systemic arterial supply to the normal basal segments of the left lower lobe
      treated by coil embolization, with long-term follow-up.
AB  - We report a case of a 41-year-old woman who underwent therapeutic embolization of
      an aberrant systemic artery of the lung. Except for chest pains immediately after
      embolization, she recovered well and has not experienced hemoptysis in the past 6
      years. In such patients, coil embolization could be an alternative choice of
      treatment, with the expectation of an excellent long-term result despite ischemia
      of the corresponding lung parenchyma.

PMID- 16958416
TI  - Spontaneous rupture of a necrotic hepatic angiosarcoma: findings on dual-phase
      computed tomography and angiography.
AB  - We present dual-phase computed tomographic (CT) and angiographic findings of a
      ruptured hepatic angiosarcoma. These tumors can be divided into two types: those
      with and those without gross central necrosis with hemorrhage. In our case, the
      tumor had gross central necrosis, and CT and angiographic findings showed a small
      number of areas with a centripetal enhancement pattern and the rest of the tumor
      with avascular areas. We found that dual-phase CT and angiographic findings are
      able to distinguish angiosarcoma, which mimics a hemangioma, as these lesions
      show avascular areas that reflect a mass with gross central necrosis.

PMID- 16958417
TI  - Omental torsion.
AB  - A 65-year-old man presented to the emergency department complaining of right
      lower abdominal pain. Abdominal computed tomography showed a whirling pattern of
      fatty streaks and vessels in the greater omentum. From this typical finding, a
      diagnosis of omental torsion was made immediately, which was confirmed by
      subsequent surgery. We report a case of surgically and pathologically proven
      omental torsion that demonstrated a typical appearance on computed tomography and
      was diagnosed preoperatively.

PMID- 16958418
TI  - Assessment of major aortopulmonary collateral arteries with multidetector-row
      computed tomography.
AB  - Multidetector-row computed tomography (MDCT) studies were performed in three
      adult patients with pulmonary atresia with a ventricular septal defect. In all
      patients, the native pulmonary arteries were absent, and the pulmonary
      circulation was totally supplied by major aortopulmonary collateral arteries
      (MAPCAs). MDCT studies with 1-mm collimation provided detailed information on
      MAPCAs and bronchial collaterals, such as the numbers and sites of origin, their
      varying diameters, their courses, and the areas of the lungs they supply. MDCT
      studies may provide an efficient road map for safe and successful selective
      catheterization and may substitute for conventional angiography in patients with
      considerable risks.

PMID- 16958419
TI  - Evaluation of vascular supply with cone-beam computed tomography during
      intraarterial chemotherapy for a skull base tumor.
AB  - A cone-beam lowers the X-ray exposure level and the contrast material dose used
      compared to those for the conventional angiography-computed tomography (angio-CT)
      technique. Herein we present a patient with a metastatic skull base bone tumor in
      which the subtraction image of cone-beam CT with a flat panel detector was useful
      for evaluating the vascular supply during superselective intraarterial
      chemotherapy. Although the image quality of cone-beam CT is poorer than that of
      conventional angio-CT, the cone-beam CT system is sufficient for clinical use.

PMID- 16958420
TI  - Radiation therapy after breast-conserving surgery.
AB  - The authors critically reviewed previous articles concerning the significance of
      breast irradiation following breast-conserving surgery in terms of the following
      subject items: indications for breast-conserving therapy, the significance and
      complications of breast irradiation, the timing of the start of breast
      irradiation, the significance of boost irradiation, the potential improvement of
      survival with systemic therapy plus breast irradiation, the significance of
      axillary dissection, indications and the significance of regional nodal
      irradiation, accelerated hypofractionated radiotherapy, omission of breast
      irradiation in low-risk patients, and future directions. In addition, our
      previously reported results of breast irradiation following breast-conserving
      surgery at the Keio University Hospital are outlined. Our newly developed
      tangential irradiation technique directed to the axilla and a recently introduced
      three-dimensional simulation technique for radiotherapy treatment planning are
      also presented.

PMID- 16958421
TI  - Diagnosis of aortic diseases using multidetector computed tomography.

PMID- 16958422
TI  - Sliding thin slab, minimum intensity projection imaging for objective analysis of
      emphysema.
AB  - PURPOSE: The aim of this study was to determine whether sliding thin slab,
      minimum intensity projection (STS-MinIP) imaging is more advantageous than thin
      section computed tomography (CT) for detecting and assessing emphysema. MATERIALS
      AND METHODS: Objective quantification of emphysema by STS-MinIP and thin-section
      CT was defined as the percentage of area lower than the threshold in the lung
      section at the level of the aortic arch, tracheal carina, and 5 cm below the
      carina. Quantitative analysis in 100 subjects was performed and compared with
      pulmonary function test results. RESULTS: The ratio of the low attenuation area
      in the lung measured by STS-MinIP was significantly higher than that found by
      thin-section CT (P < 0.01). The difference between STS-MinIP and thin-section CT
      was statistically evident even for mild emphysema and increased depending on
      whether the low attenuation in the lung increased. Moreover, STS-MinIP showed a
      stronger regression relation with pulmonary function results than did thin
      section CT (P < 0.01). CONCLUSION: STS-MinIP can be recommended as a new
      morphometric method for detecting and assessing the severity of emphysema.

PMID- 16958423
TI  - Automatic volumetric measurement of segmented brain structures on magnetic
      resonance imaging.
AB  - PURPOSE: The purpose of this study was to produce a fully automatic volumetric
      segmented brain image system (AVSIS) and to evaluate its utility for measuring
      hippocampal volumes and total intracranial volume (TIV). MATERIALS AND METHODS:
      We developed a combination technique comprising an anatomical standardization
      technique to measure TIV, whole brain volume (WBV), and hippocampal volume
      obtained by magnetic resonance (MR) imaging. Altogether, 15 healthy volunteers
      and 15 patients with Alzheimer's disease (AD) underwent three-dimensional spoiled
      gradient echo (3D-SPGR) imaging. Three measurements were performed by manual
      volumetry as the gold standard, a previous semiautomatic method, and our new
      method, AVSIS. RESULTS: WBV and hippocampal volume in the AD group were
      significantly smaller than those in the healthy volunteer group measured by the
      semiautomatic method, manual method, and AVSIS. Each volume measured by AVSIS or
      semiautomatic method correlated with that measured by the manual method. The
      correlation coefficients between TIVs, WBVs, or hippocampal volumes measured by
      AVSIS and the manual method were 0.910, 0.902, and 0.918, respectively; the
      correlation coefficients between TIVs, or WBVs, measured by the previous
      semiautomatic method and the manual method were 0.875, and 0.886, respectively.
      CONCLUSION: We developed a system for a fully automatic measurement of segmented
      brain structures and obtained good results.

PMID- 16958424
TI  - Risk factors for enlargement of cardiac silhouette on chest radiography after
      radiotherapy for esophageal cancer.
AB  - PURPOSE: To evaluate the incidence and risk factors of enlargement of cardiac
      silhouette on chest radiographs after radiotherapy for esophageal cancer.
      MATERIALS AND METHODS: We analyzed 67 patients with esophageal cancer who
      received external beam radiation therapy with a total dose of >or=50 Gy and were
      followed for >or=6 months. Sixteen patients received radiation alone, and the
      remaining 51 received chemoradiotherapy. The difference between the
      cardiothoracic ratio (CTR) on the pretreatment chest radiograph and that on the
      posttreatment radiograph with maximum cardiac silhouette for each patient was
      used for the analysis. RESULTS: The average maximum increase in CTR for the
      entire group was 4.5%, which was statistically significant. Only the area of the
      cardiac silhouette in the initial radiation field was a significant risk factor
      for enlargement of the cardiac silhouette. Pericardial effusions were observed in
      all patients who underwent computed tomography with severe enlargement of the
      cardiac silhouette. CONCLUSION: The CTR value significantly increased after
      radiotherapy for esophageal cancer. Radiation-induced pericardial effusion may be
      the main cause of enlargement of the cardiac silhouette. The irradiated cardiac
      area was the only significant risk factor for enlargement of the cardiac
      silhouette; the use of chemotherapy was not.

PMID- 16958425
TI  - Measurement of the apparent diffusion coefficient in the liver: is it a reliable
      index for hepatic disease diagnosis?
AB  - PURPOSE: The aim of this study was to determine the validity of the hepatic
      apparent diffusion coefficient (ADC) measurement. The influence of differences in
      measured location and administration of Buscopan (hyoscine butylbromide) for ADC
      were assessed. MATERIALS AND METHODS: SENSE-DWI (b = 0, 500) was obtained before
      and after Buscopan administration to 30 patients suspected of having a liver
      tumor. In this sequence, respiration gating was employed, but cardiac triggering
      was not. ADC measurement was performed in the hepatic parenchyma of both right
      and left lobes in selected slices. A statistical analysis was performed to
      estimate the correlation among ADC, measured location, Buscopan, and pulse rate.
      The images were visually evaluated to categorize the subcardiac signal loss in
      the left lobe. RESULTS: The ADC showed higher values in the left lobe than in the
      right lobe in both pre- and postloaded studies (P < 0.001). In a comparison
      between ADCs in the pre- and postloaded studies, the differences were not
      significant in the left lobe (P = 0.93) or the right lobe (P = 0.41). No
      correlation was noted between ADCs and the pulse rate. Visual evaluation revealed
      that the subcardiac signal loss was more prominent in the postloaded study.
      CONCLUSION: ADC measurement of the left hepatic lobe was far more incorrect than
      that of the right lobe if cardiac gating was not employed. The administration of
      Buscopan worsened the image quality of the left lobe and made visual evaluation
      difficult.

PMID- 16958426
TI  - Dialyzability of gadodiamide in hemodialysis patients.
AB  - PURPOSE: The aim of this study was to evaluate the contrast enhancement,
      pharmacokinetics, dialyzability, and safety of gadodiamide in patients on
      hemodialysis. MATERIALS AND METHODS: Thirteen hemodialysis patients with
      abdominal disease were examined after receiving intravenous gadodiamide (0.1
      mmol/kg body weight) by magnetic resonance imaging (MRI) and were dialyzed at l,
      3, 5, and 8 days. Blood samples were obtained immediately before, during, and at
      the end of the first hemodialysis session and immediately before and at the end
      of the next three sessions. The complete blood count, blood biochemistry, beta2
      microglobulin, and gadolinium were measured. Dialysis of urea, creatinine, and
      gadolinium during the first hemodialysis session was assessed. Precontrast and
      postcontrast MRI and Gd-enhanced MR angiography (MRA) images were reviewed and
      visually evaluated by two radiologists; their evaluation was based on consensus.
      RESULTS: Gadodiamide did not cause any changes in renal function. An average of
      73.8%, 92.4%, and 98.9% of the gadodiamide dose was eliminated by the end of the
      first, second, and third hemodialysis sessions, respectively. The average half
      time of gadodiamide was 1.93 h (SD 0.55). The mean clearance of gadodiamide
      during hemodialysis was 63.5 ml/min (SD 21.9). There were no side effects related
      to the injection of gadodiamide. In all cases, diagnosable MRI and MRA images
      were obtained after gadodiamide injection in the hemodialysis patients.
      CONCLUSION: In hemodialysis patients, gadodiamide achieves diagnosable images. It
      is dialyzable and can be used safely without measures to increase excretion.

PMID- 16958427
TI  - Ectopic cervical thymus in an infant.
AB  - We report a case of accessory cervical thymus presenting as a unilateral neck
      mass in a 2-month-old boy. Ultrasonography (US) showed a mass isoechogenic to
      muscle in the left neck. Computed tomography (CT) revealed a well-defined, mildly
      enhanced mass located anterior to the sternocleidomastoid muscle, anterolateral
      to the carotid sheath, and posterior to the submandibular gland. On magnetic
      resonance imaging (MRI), the mass was isointense to muscle on T1-weighted images
      and hyperintense to muscle on T2-weighted images. Diffusion-weighted images
      showed relatively low apparent diffusion coefficient (ADC) values, and the mass
      was slightly enhanced after administration of contrast material. We suspected
      ectopic thymus, but we could not exclude the possibility of a malignant lesion.
      Therefore, the tumor was surgically resected. The histological diagnosis was
      ectopic cervical thymus. Ectopic thymus should be included in the differential
      diagnosis of a submandibular or cervical mass in infants. US and MRI can provide
      useful information for the diagnosis of ectopic cervical thymus.

PMID- 16958428
TI  - Intense accumulation of gallium-67 citrate in pancreatic endocrine tumor.
AB  - We report intense accumulation of gallium-67 (Ga-67) citrate in a pancreatic
      endocrine tumor. A 69-year-old woman was admitted because of cough, fever, and
      weight loss. An abdominal enhanced computed tomography (CT) scan revealed a large
      tumor located between the liver and pancreas as well as swollen paraaortic lymph
      nodes. Whole-body scintigraphy with Ga-67 revealed intense accumulation in the
      upper abdomen corresponding to the mass, as well as in the midabdomen and the
      mediastinal lesion. Percutaneous needle biopsy was performed, and the diagnosis
      was adenocarcinoma of the pancreas. The patient's condition deteriorated, and she
      died 2 months after admission. The pathological examination at autopsy revealed a
      pancreatic endocrine tumor. No report has described findings of Ga-67 citrate
      scintigraphy of pancreatic endocrine tumors. Pancreatic endocrine tumor should be
      included in a differential diagnosis when such scintigraphic findings are
      encountered.

PMID- 16958429
TI  - Magnetic resonance findings of bile duct adenoma with calcification.
AB  - Computed tomographic (CT) and magnetic resonance (MR) appearances of bile duct
      adenoma (BDA in a patient who underwent partial hepatectomy of segment 8 are
      presented. BDA showed a ring-shaped hyperdense area suggesting calcification and
      ring enhancement on CT. It appeared hypointense on both T1- and T2-weighted MR
      images. Preoperatively, the diagnoses considered included metastatic carcinoma,
      cholangiocarcinoma, tuberculosis, and rare tumors such as epithelioid
      hemangioendothelioma. The radiological findings were confirmed by pathological
      investigation.

PMID- 16958430
TI  - Early disappearance of calcification in posterior paraspinal muscles in a patient
      with rhabdomyolysis associated with neuroleptic malignant syndrome.
AB  - We report computed tomography (CT) findings that demonstrated early disappearance
      of ectopic calcification in the bilateral posterior paraspinal muscles in a
      patient with rhabdomyolysis. A 37-year-old man with acute renal failure due to
      rhabdomyolysis caused by neuroleptic malignant syndrome underwent studies with CT
      and bone scintigraphy. First, bone scintigraphy showed high radiotracer uptake in
      bilateral posterior paraspinal muscles; then CT demonstrated ectopic
      calcification in those muscles. After 2.5 months, CT showed that the
      calcification had completely disappeared. Bone scintigraphy anticipated
      calcification, and CT demonstrated a unique course of early disappearance of the
      calcification.

PMID- 16958431
TI  - Hepatocellular carcinoma with a prominent vascular scar in the center: MR imaging
      findings.
AB  - We report herein a case of hepatocellular carcinoma (HCC) with a prominent
      central scar. Dynamic CT and MRI studies revealed a hypervascular liver mass and
      a washout of contrast material in the delayed phase. The tumor center showed
      particular hyperintensity on T2-weighted images and delayed or prolonged
      enhancement. The surgical specimen revealed moderately differentiated HCC with a
      central scar. The central scar consisted of prominent vascular channels and loose
      fibrous tissue, indicative of a vascular scar. We should understand MR imaging
      findings of this type of central scar in the HCC.

PMID- 16958432
TI  - Midline cystic malformations of the brain: imaging diagnosis and classification
      based on embryologic analysis.
AB  - This article describes a classification and imaging diagnosis of intracranial
      midline cystic malformations based on neuroembryologic analysis. Midline cystic
      malformations are classified into two categories from an embryologic point of
      view. In one category, the cyst represents expansion of the roof plate of the
      brain vesicle, and in the other the cyst consists of extraaxial structures such
      as an arachnoid membrane or migrating ependymal cells. Infratentorial cysts, such
      as the Dandy-Walker cyst or Blake's pouch cyst, and supratentorial cysts, such as
      a communicating interhemispheric cyst with callosal agenesis or a dorsal cyst
      with holoprosencephaly, are included in the first category. Infratentorial
      arachnoid cavities, such as the arachnoid cyst, arachnoid pouch, and mega
      cisterna magna, are in the second category. Noncommunicating interhemispheric
      cysts, such as interhemispheric arachnoid cyst or ependymal cyst, with callosal
      agenesis are also in the second category. A careful review of embryologic
      development is essential for understanding these midline cysts and for making a
      more accurate radiologic diagnosis.

PMID- 16958433
TI  - Imaging diagnosis and fundamental knowledge of common brain tumors in adults.
AB  - The most common primary brain tumors in Japanese adults are meningiomas, gliomas,
      pituitary adenomas, and schwannomas, which together account for 84.0% of all
      primary brain tumors. The typical imaging findings of these tumors are well known
      by radiologists; therefore, the clinical and pathological issues, including
      terminology, genetics, and relation to hormones are discussed in this article.
      Other diseases important for the differential diagnoses are also mentioned. The
      molecular genetic analysis of brain tumors has recently become important. For
      instance, genetic analysis is important for differentiating oligodendroglial
      tumors from astrocytic tumors, and the gene mutation predicts response to
      chemotherapy for anaplastic oligodendrogliomas. Background factors such as
      hormones, history of cranial irradiation, and medications influence oncogenesis,
      tumor growth, and tumor appearances as seen by imaging modalities. A differential
      diagnosis with knowledge of the above may have some advantages over diagnoses
      based on imaging findings alone. Nonneoplastic diseases such as abscesses and
      demyelinating diseases may mimic gliomas. Pituitary adenomas may be confused with
      nonneoplastic conditions such as physiological hypertrophy and Rathke's cleft
      cyst. Such misdiagnoses would result in a treatment protocol very different from
      what would be suitable. Such conditions should be carefully distinguished from
      neoplasms.

PMID- 16958434
TI  - Clinical evaluation of impingement: what to do and what works.
AB  - Theories about the etiologies of anterior and lateral shoulder pain have changed
      greatly since "impingement disease" was first described. It is thought that such
      pain may be caused by contact between the rotator cuff and the acromion and
      coracoacromial ligament, but the exact pathophysiology of rotator cuff disease
      remains unclear. The shoulder is notoriously difficult to examine because of the
      variability of the physical findings in patients with rotator cuff disease. New
      concepts of impingement, such as coracoid impingement and internal impingement,
      have been advanced. Although no test is definitive for all causes of anterior and
      lateral shoulder pain, as the pathophysiology of these conditions becomes better
      understood the ability to evaluate them clinically also improves.

PMID- 16958435
TI  - Shoulder impingement revisited: advanced concepts of pathomechanics and
      treatment.
AB  - Subacromial impingement is a common disorder of the shoulder that is still poorly
      understood. Knowledge of the pathogenesis of this condition has expanded greatly
      since it was described by Neer 40 years ago. Research has shown that multiple
      factors contribute to the development of rotator cuff disease. New investigations
      are exploring this disorder with input from several scientific disciplines. It is
      essential that orthopaedic surgeons treating patients with subacromial
      impingement understand the underlying mechanisms, the new research, and the
      current trends in management of this disease.

PMID- 16958436
TI  - Internal impingement of the shoulder.
AB  - Internal impingement has been proposed as a cause of dead arm syndrome. Recent
      information, however, suggests that internal impingement is not pathologic; it is
      a natural restraint to hyperexternal rotation. The loss of internal impingement
      is pathologic, allowing hyperexternal rotation with hypertwist and fatigue
      failure of rotator cuff fibers. The "dead arm" of the throwing athlete may be
      caused by superior labrum anterior and posterior lesions or by SICK scapula
      syndrome (scapular dyskinesis). Superior labrum anterior and posterior lesions
      typically require arthroscopic repair, whereas the scapular dyskinesis can
      generally be treated with a focused rehabilitation program. Open anterior
      stabilization surgery should not be used to treat dead arm syndrome.

PMID- 16958437
TI  - Scapular involvement in impingement: signs and symptoms.
AB  - Normal scapular motion is closely integrated with arm motion to provide efficient
      scapulohumeral rhythm in shoulder function. This rhythm is often disrupted in
      patients with symptoms and signs of shoulder impingement. A large percentage of
      patients with shoulder impingement have scapular dyskinesis and alterations in
      the normal resting position of the scapula or in dynamic scapular motion.
      Scapular dyskinesis usually manifests as a loss of control in the motions of
      scapular external rotation and the translation of scapular retraction. This loss
      of control results in alteration in timing and magnitude of acromial upward
      rotation, excessive antetilting of the glenoid, and loss of maximal rotator cuff
      muscle activation capability. These pathophysiologic and pathomechanical
      alterations cause or increase the dysfunction associated with impingement.
      Scapular dyskinesis may have proximal or distal causative factors. Proximal
      factors are mainly associated with muscle factors, and can usually be treated
      with rehabilitation. Distal factors are mainly caused by internal derangements of
      joints and frequently require surgical treatment followed by appropriate
      rehabilitation. Physical examination techniques that specifically evaluate
      scapular dyskinesis can identify the causative factors and guide treatment and
      rehabilitation strategies.

PMID- 16958438
TI  - Diagnosis and management of massive rotator cuff tears: the surgeon's dilemma.
AB  - Several studies have documented high success rates following the surgical
      treatment of full-thickness rotator cuff tears. Historically, however, less
      favorable and predictable results have been found in the treatment of massive
      tears (>5 cm) compared with small and medium sized tears. Determining the most
      appropriate treatment for a patient with a massive rotator cuff tear can be
      challenging because of inconsistent outcome results. Some patients function well
      with nonsurgical treatment of massive tears, some have initially favorable
      results from surgical debridement of tears without repair that then deteriorate
      over time, and other patients who are surgically treated continue to maintain
      good function despite documented retears. Nonsurgical treatment of massive
      rotator cuff tears may be suitable for elderly patients with chronic tears and
      limited functional goals below shoulder level. Surgical debridement without
      repair of the tear may be considered for patients with low physical demands whose
      predominant symptom is pain. Surgical repair is recommended for patients who
      require maximal postoperative function, particularly for overhead activities.
      Open repairs have a lower rate of rerupture than arthroscopic repairs; however,
      arthroscopic repair offers the benefits of decreased morbidity and decreased risk
      of postoperative deltoid detachment. Early studies of arthroscopic repairs have
      shown good functional results; however, there has been a high incidence of
      retears. Tendon transfers and other reconstruction techniques may offer
      improvements in certain salvage cases, but results of these procedures are
      inferior to those for primary repair. Preservation of the coracoacromial arch
      should be considered in all forms of treatment of massive rotator cuff tears to
      avoid the devastating complication of superior humeral head escape.

PMID- 16958439
TI  - Arthroscopic approach to massive rotator cuff tears.
AB  - The treatment of a patient with a painful massive rotator cuff tear can be
      challenging. Massive tears exceed 5 cm in length and involve partial or complete
      tearing of three tendons. The arthroscopic approach provides a minimally invasive
      technique to evaluate the tear, mobilize and repair tendons, and improve symptoms
      without disruption of the deltoid. The arthroscopic technique can create a low
      tension repair. The reduction of postoperative motion provides the best
      environment for tendon-to-bone reattachment. Procedures that have reduced rates
      of adhesion formation allow for this protection with a minimal risk of stiffness.
      Reduction of the boutonniere effect of superior head migration leads to improved
      arm elevation. Strength deficits are common and relate to muscle and tendon
      deterioration that may not be reversible, even with successful closure of the
      tear. Weakness caused by suprascapular neuropathy may improve after the position
      and length of the posterosuperior cuff tendons are reestablished. Arthroscopic
      options include rotator cuff repair, partial cuff repairs, xenografts,
      decompression, debridement, biceps tenotomy, tenodesis, and use in autografting.

PMID- 16958440
TI  - Shoulder arthritis in the young adult: arthroscopy to arthroplasty.
AB  - Young adult patients with shoulder arthritis present challenging treatment
      decisions for the orthopaedic surgeon. Patients treated with shoulder
      arthroplasty have the youngest average age of all patients who undergo joint
      arthroplasty. However, in the young, active patient or in those without advanced
      disease, joint arthroplasty may not be appropriate. Arthroscopic treatment or
      interposition arthroplasty may provide symptomatic relief without radically
      compromising future procedures.

PMID- 16958441
TI  - The management of acromioclavicular joint osteoarthrosis: debride, resect, or
      leave it alone.
AB  - The acromioclavicular joint is a small, diarthrodial joint that can cause
      significant pain. A thorough patient history, careful physical examination, and
      the judicious use of selective injections are critically important to making an
      accurate diagnosis. Many radiographic findings are unreliable in determining the
      reasons for a symptomatic acromioclavicular joint. Recent controversy surrounding
      this joint has centered on the clinical question: should the acromioclavicular
      joint be left alone, debrided, or resected? A review of the anatomy,
      pathophysiology, biomechanics, diagnostic criteria, and treatment options for
      patients with disorders of the acromioclavicular joint can provide information to
      answer this question.

PMID- 16958442
TI  - Elbow arthroscopy.
AB  - Many surgeons avoid performing elbow arthroscopy because the elbow's unique
      anatomy and proximity to multiple neurovascular structures make it a technically
      demanding procedure with the potential for complications. However, recent
      advances in surgical technique and equipment have made arthroscopy easier and
      safer to perform and have expanded the indications for arthroscopic evaluation
      and treatment of elbow disorders. Careful patient selection, examination, and
      portal placement are critical to minimizing the potential for complications.
      Other techniques to decrease the incidence of complications from elbow
      arthroscopy include accurate preoperative outlining of anatomic landmarks,
      appropriate joint distention achieved by placing the patient's elbow in 90
      degrees of flexion before portal placement, and the use of retractors to protect
      nerves and to maintain visualization and control of instruments during the
      procedure.

PMID- 16958443
TI  - Elbow arthroscopy: treatment of the thrower's elbow.
AB  - The athlete's elbow has been described as one of the last frontiers in
      orthopaedic sports medicine. It has been considered separately from other
      athletic injuries because of the unique constellation of pathology that results
      from repetitive overhead throwing. Tremendous gains in understanding the complex
      interplay between the dynamic and static stabilizers of the athlete's elbow have
      occurred over the past decade. The desire to treat these injuries in a minimally
      invasive manner has driven the development of techniques and instrumentation for
      elbow arthroscopy, a successful and essential technique in the treatment of the
      thrower's elbow. Medial collateral ligament injuries, ulnar neuritis, valgus
      extension overload with osteophyte formation and posteromedial impingement,
      flexor pronator strain, medial epicondyle pathology, and osteochondritis
      dissecans of the capitellum have all been described as consequences of the
      overhead throwing motion. In addition, loose body formation, bony spur formation,
      and capsular contracture can each be present in conjunction with these conditions
      or as isolated entities. Not all pathology in the thrower's elbow is amenable to
      arthroscopic treatment; however, the clinician must be familiar with all of these
      conditions to form a comprehensive differential diagnosis for an athlete with
      elbow pain. The surgeon treating the athlete's elbow should be comfortable with
      both open and arthroscopic treatments. An understanding of the anatomy and
      biomechanics of the thrower's elbow is essential for good patient care. The
      preoperative evaluation should focus on a thorough history and physical
      examination, as well as specific diagnostic imaging modalities.

PMID- 16958444
TI  - Arthroscopic treatment of the arthritic elbow.
AB  - Elbow arthroscopy is now being used with greater frequency to treat arthritis and
      contractures. The procedure is technically demanding and the potential for injury
      to neurovascular structures remains a concern. Potential advantages of
      arthroscopic treatment include improved articular visualization and decreased
      postoperative pain. Patients may also benefit from decreased morbidity and a
      faster postoperative recovery. Elbow arthroscopy can be performed for removal of
      loose bodies, resection of symptomatic plica, release of the capsule in patients
      with contracture, removal of osteophytes, treatment of synovectomy in
      inflammatory arthritis, treatment of osteochondritis dissecans, debridement of
      lateral epicondylitis, and treatment of elbow fractures.

PMID- 16958445
TI  - Malunion and nonunion of the metacarpals and phalanges.
AB  - The management of nonunion and malunion in the metacarpals and phalanges is
      influenced by the multiple gliding structures and the propensity for stiffness,
      the ability of adjacent digits to substitute functionally for compromised digits,
      the small size of the bones, and associated complications. Amputation and
      arthrodesis are useful treatment options for nonunions in the hand because they
      are nearly always atrophic, are frequently associated with joint stiffness and
      tendon adhesions, and often occur in digits with poor nerve function,
      vascularity, or skin cover. Surgical fixation with autogenous bone grafts and
      stable internal fixation has a high union rate with resultant restoration of
      alignment and stability, but achieves modest improvements in motion. Slightly
      larger implants than one would use for a fracture at the same size and structural
      (corticocancellous) bone grafts are useful for obtaining adequate stability to
      initiate immediate exercises in order to limit the potential for stiffness.
      Malunion is treated only when doing so offers useful functional advantages. The
      optimal timing and site of intervention are debatable; however, it is usually
      easiest to restore alignment when operating at the site of the original fracture
      and prior to complete consolidation of the fracture. This is particularly true
      for articular fractures. Once these fractures are mature, it may be preferable to
      perform an extra-articular osteotomy. If a late intra-articular osteotomy is
      performed, it should be done in such a way as to create large fragments that are
      easier to repair and more likely to retain their blood supply.

PMID- 16958446
TI  - Pelvic and femoral osteotomy in the treatment of hip disease in the young adult.
AB  - Osteotomies of the pelvis and upper femur play a useful and enduring role in the
      overall management of posttraumatic and developmental conditions of the hip.
      Rotational osteotomies of the pelvis have supplanted intertrochanteric
      osteotomies for treatment of most dysplasia-related conditions. In particular,
      the Bernese (Ganz) periacetabular osteotomy with lateral muscle sparing has
      emerged as the most effective and widely used pelvic osteotomy. Other methods,
      such as the Tonnis juxta-articular and triple innominate, also can be successful.
      These procedures have a risk profile that demands respect for the possible
      occurrence of significant complications and outcomes that are not uniformly
      excellent. Once significant arthritis is present, total hip arthroplasty is the
      procedure of choice in most instances. On the femoral side, the effectiveness of
      valgus osteotomy for femoral neck nonunion is unquestioned. Precollapse
      osteonecrosis is not a contraindication. Limb-length inequalities, malrotations,
      and displacements of posttraumatic deformities can be uniquely benefited by
      intertrochanteric osteotomy. Grade II slipped capital femoral epiphysis, Legg
      Calve-Perthes disease, and osteonecrosis sometimes can be effectively treated
      with intertrochanteric osteotomy. All osteotomies should be planned and performed
      in a manner that anticipates the possible need for future conversion to total hip
      replacement.

PMID- 16958447
TI  - Hip joint-preserving surgery: beyond the classic osteotomy.
AB  - It has been postulated that hip osteoarthritis is often caused by developmental
      anatomic deformities. Recent studies have demonstrated that relatively subtle
      anatomic abnormalities such as acetabular retroversion, acetabular overcoverage,
      and decreased offset of the femoral head-neck junction also may lead to pain and
      osteoarthritis. Advances in surgical techniques such as the periacetabular
      osteotomy, safe surgical dislocation of the hip, and hip arthroscopy have
      provided the surgeon with effective and safe tools to correct these anatomic
      problems. Clinical and radiographic techniques are used to identify these
      anatomic abnormalities.

PMID- 16958448
TI  - Nonarthroplasty surgical treatment of hip osteoarthritis.
AB  - The two conditions that give rise to osteoarthritis of the hip are dysplasia and
      nondysplasia. Dysplasia, commonly associated with anterolateral acetabular
      deficiency, may lead to osteoarthritis in 40% of patients in the United States
      with this condition. In a distinct category of patients with so-called idiopathic
      arthritis, there is no apparently identifiable cause for osteoarthritis. There is
      emerging evidence that subtle morphologic abnormalities around the hip, resulting
      in femoroacetabular impingement, may often be a contributing factor to
      osteoarthritis in young patients.

PMID- 16958449
TI  - Surgical treatment of osteonecrosis of the hip.
AB  - Various surgical procedures are used in patients with osteonecrosis of the hip.
      Patients with precollapse of the femoral head are generally treated with head
      preserving procedures (core decompression, various bone grafting techniques, and
      osteotomies), whereas those with collapse of the femoral head and/or arthritis
      may require arthroplasty. The arthroplasty options available include limited
      femoral resurfacing arthroplasty, metal-on-metal resurfacing arthroplasty, or
      total hip replacement. The indications, techniques, and early outcomes of some of
      these procedures for treatment of osteonecrosis of the hip merit discussion.

PMID- 16958450
TI  - Total hip arthroplasty in the young patient.
AB  - Total hip arthroplasty was originally indicated for older, sedentary patients
      because of concerns that catastrophic wear and failure would occur in younger and
      more active patients. With advances in implant design, tribology, and surgical
      technique, total hip arthroplasty has now become a viable option for younger
      patients seeking excellent pain relief and improvement in function. Long-term
      studies are needed to evaluate the outcome of hip arthroplasty in younger
      patients using the modern generation of implants and bearing surfaces.

PMID- 16958451
TI  - Alternative bearing surfaces in total hip arthroplasty.
AB  - Although total hip arthroplasty has been shown to be an effective surgical
      procedure, long-term outcomes are compromised by wear of the bearing surfaces.
      Recent technologic advances have been made in the design of bearing surfaces that
      offer extended performance to these artificial joints.

PMID- 16958452
TI  - Achieving optimal cementless fixation in total hip arthroplasty.
AB  - Achieving optimal cementless fixation of the components is essential to the long
      term success of total hip arthroplasty. Optimal fixation provides patients with
      predictable and durable results. The recent emphasis on minimally invasive
      surgery has focused attention on short-term goals, such as rapid rehabilitation
      and early discharge from the hospital. The ultimate goal of total hip
      arthroplasty, however, is long-term pain relief and function. Minimally invasive
      surgery should not compromise long-term outcomes for short-term achievements.
      Gentle, safe, and adequate exposure is required for proper component placement
      and for obtaining optimal initial fixation.

PMID- 16958453
TI  - In the absence of evidence--why bother? A literature review of minimally invasive
      total hip replacement surgery.
AB  - Two new total hip replacement (THR) procedures have been termed minimally
      invasive. It is claimed that these smaller incision techniques reduce soft-tissue
      trauma, decrease postoperative pain and blood loss, speed recovery, and reduce
      the length of the hospital stay compared with hip replacement using the standard
      incision technique. These new procedures use either one small 6- to 10-cm
      incision through a posterior, lateral, or anterior approach or two very small (a
      2.5 cm posterior incision for placement of the femoral component and a 5-cm
      anterior incision for placement of the acetabular component) incisions to
      accomplish the same THR procedure that requires a standard length incision of 15
      to 20 cm. Controversy exists on whether these small incision THRs are actually
      minimally invasive. It is debated whether a small skin incision that requires the
      application of high forces on the soft tissues for exposure of the joint but less
      muscle dissection will produce less overall trauma to the patient than a larger
      incision with wider muscle dissection but with lower retraction forces. If small
      incision THR techniques are less traumatic overall, then they should produce less
      pain, lower transfusion requirements, a shorter hospital stay, and a faster
      recovery for patients. The other important issues regarding small incision
      procedures are whether the decreased visualization provided by these techniques
      is adequate to prevent a higher complication rate from damage to the surrounding
      neurovascular structures and outcomes that are equivalent to those found for THR
      using the standard technique. A review of the literature to date provides no
      convincing evidence of any significant advantages of small incision THR compared
      with standard incision THR other than a shorter surgical scar. Comparison studies
      that prove both significant advantages and low complication rates for small
      incision THR are needed before these procedures can be recommended for general
      use.

PMID- 16958454
TI  - Minimally invasive or limited incision hip replacement: clarification and
      classification.
AB  - The goal of total hip replacement is to provide a pain-free, well-fixed, stable,
      long-lasting arthoplasty. Length of hospital stay, recovery time, and incision
      length are important factors related to the success of the procedure. As the
      procedure has evolved, the use of limited incision surgery has grown. A uniform
      classification system for less invasive approaches to total hip replacement will
      allow similar approaches to be grouped together and help surgeons to select the
      best approach.

PMID- 16958455
TI  - The limited incision, anterolateral, intermuscular technique for total hip
      arthroplasty.
AB  - Limited incision total hip arthroplasty has potential advantages over traditional
      techniques. Many new approaches have been advocated, however, each new approach
      has a number of drawbacks. A technique using a single incision with an
      anterolateral, intermuscular approach offers attractive advantages including the
      use of the more familiar lateral positioning for the patient and a short learning
      curve for the surgeon. Also, intraoperative fluoroscopy is not required and the
      surgeon can perform a trial reduction and can extend the approach if necessary.

PMID- 16958456
TI  - Minimally invasive total hip arthroplasty: the posterior approach.
AB  - Minimally invasive total hip replacement is probably a misnomer and the procedure
      is better termed less invasive total hip replacement. The mini-posterior approach
      is a modification of a standard approach, with a smaller skin incision and less
      deep tissue dissection. The gluteus maximus tendon is not released and the
      quadratus femoris muscle is minimally violated. Blood loss has been documented to
      be less and early recovery is facilitated. Compared with the standard posterior
      approach, there have been fewer complications associated with the modified
      approach.

PMID- 16958457
TI  - Two-incision minimally invasive total hip arthroplasty: techniques and results to
      date.
AB  - The two-incision minimally invasive technique for total hip arthroplasty is
      described in detail, with attention to pearls of technique, for a prospective
      group of 200 patients, as well as a matched-pair group of 43 patients who
      underwent either the two-incision procedure or the mini-incision (single-incision
      posterior) procedure. The importance of a total hip critical pathway is
      emphasized, and the economic benefits are presented. Results reveal that the two
      incision and mini-incision techniques have acceptable complication rates, are
      cost effective, and are beneficial to the patient, with reduced hospital stays,
      high patient satisfaction, and earlier return to function.

PMID- 16958458
TI  - Evaluation of patients with pain following total hip replacement.
AB  - Ongoing pain after total hip replacement is a source of frustration to both the
      patient and the surgeon. A structured approach to the evaluation of patients with
      postoperative pain is essential. The key to such an approach is a meticulous
      patient history and physical examination. The results of relevant investigations
      allow an effective treatment plan to be quickly implemented.

PMID- 16958460
TI  - Optimally invasive exposure in revision total hip arthroplasty: a guide to
      selection and technique.
AB  - Revision total hip arthroplasty requires a careful surgical plan. Selection of
      the appropriate exposure is an essential step for success. Exposure is important
      not only for the complete and safe visualization and extraction of components and
      cement, but also for the achievement of a stable construct at the end of the
      procedure. In addition, controlled exposure minimizes intraoperative
      complications and bone and soft-tissue damage, essential considerations for
      eradication of infection. Three questions need to be addressed at the
      preoperative stage: (1) Is this a straightforward revision that can be handled
      with a standard approach? (2) Is this a more complex revision requiring an
      extensile exposure? (3) Is this an unusual revision requiring special techniques
      to allow adequate access that cannot be obtained using standard extensile
      techniques? Each group of exposures presents three further possibilities, each of
      which has specific indications, advantages, and disadvantages. In conjunction
      with the preoperative analysis, this knowledge should enable the revision surgeon
      to select the most appropriate approach, resulting in optimal exposure for each
      individual revision scenario.

PMID- 16958459
TI  - Preoperative planning for revision total hip arthroplasty.
AB  - Revision total hip arthroplasty is associated with more perioperative
      complications and unexpected findings than are encountered during primary total
      hip arthroplasty. Special instruments, implants, bone grafts, and other
      accessories may be required to treat complex problems that arise during revision
      surgery. Preoperative planning is important to anticipate potential complications
      and to ensure that all possible needed materials are readily available during
      surgery. Patients and their families also should be counseled on the specific
      additional risk factors involved in this complex surgery. An organized approach
      to revision total hip arthroplasty helps to reduce surgical time, minimize risks,
      decrease the stress level of the entire surgical team, and to increase the rate
      of successful outcomes for patients.

PMID- 16958461
TI  - Removal of well-fixed cementless components.
AB  - Removal of stable, osseointegrated cementless components can be a challenge for
      the orthopaedic surgeon. Careful preoperative planning to assess the location and
      extent of the bone ingrowth or ongrowth as well as ensuring that the appropriate
      instrumentation is available in the operating room can help minimize
      complications when performing these procedures.

PMID- 16958462
TI  - Managing bone loss in revision total hip arthroplasty: the acetabulum.
AB  - Osteolysis is the greatest threat to the viability of modern acetabular implants.
      The etiology and natural history of osteolysis remain unknown. Patients with
      cementless implants who have osteolysis are challenging to treat. There are no
      standards for follow-up methods or frequency, and there is little evidence to
      support timing of the decision to begin treatment in these patients. The natural
      history of proposed treatment options is also unknown. Reconstruction of the
      acetabulum in the presence of bone loss is difficult. Classifications have been
      developed to guide management. Multiple options exist for revision acetabular
      surgery, and it is important to understand the rationale and data in support of
      these options. A review of the literature was undertaken and algorithms were
      developed to help address acetabular bone loss in patients undergoing revision
      surgery.

PMID- 16958463
TI  - Management of acetabular bone loss.
AB  - Acetabular bone loss is a common complication associated with revision total
      joint replacement. Successful surgical management is enhanced by a systematic
      classification of bony defects. A variety of implants, fixation strategies,
      surgical techniques, and graft materials are required to address the spectrum of
      reconstructive complications encountered at revision surgery.

PMID- 16958464
TI  - Managing bone loss in acetabular revision.
AB  - The management of bone loss encountered during acetabular revision remains
      challenging. In order to obtain a successful surgical result, preoperative
      planning is required to estimate the severity and location of bone defects. Most
      acetabular revisions can be treated with the use of a cementless hemispherical
      component. However, a successful surgical reconstruction requires component
      stability. Depending on the degree of bone loss, the surgical reconstruction may
      require the use of cancellous or structural bone graft, acetabular augmentation,
      an acetabular cage, a custom implant, or an acetabular transplant.

PMID- 16958465
TI  - Hip arthroscopy: indications, outcomes, and complications.
AB  - Hip arthroscopy is technically demanding, with a steep learning curve, and
      requires special distraction tools and operating equipment. Access to the hip
      joint is difficult because of the resistance to distraction resulting from the
      large muscular envelope, the strength of the iliofemoral ligament, and the
      negative intra-articular pressure. This operation should not be done without
      specific education in its methods.

PMID- 16958466
TI  - New frontiers in hip arthroscopy: the role of arthroscopic hip labral repair and
      capsulorrhaphy in the treatment of hip disorders.
AB  - Hip pain can be caused by multiple pathologies. In younger patients, injuries to
      the acetabular labrum are a major source of pain. The labrum, with its
      proprioreceptors and neuroreceptors, can be a source of hip pain but also can
      cause mechanical symptoms. A labral tear can also contribute to hip instability.
      Labral repair and capsular treatment are important interventions to optimize hip
      joint function. Labral tears can be treated with debridement and surgical repair.
      A bioabsorbable suture anchor is needed to stabilize the fibrocartilaginous
      tissue back to the rim of the acetabulum when the labrum is detached from the
      bone. The goal of arthroscopic treatment of a torn labrum is to relieve pain by
      eliminating the unstable flap tear that causes hip discomfort. For capsular
      laxity, focal thermal capsulorrhaphy and capsular plication are performed to
      reduce capsular redundancy. The goals of these treatments are to maintain the
      function of the hip joint, return the patient to activity, and decrease the
      development of premature arthrosis.

PMID- 16958467
TI  - Hip arthroscopy by the lateral approach.
AB  - Performing hip arthroscopy with the patient in the lateral decubitus position is
      advantageous in aiding in visualization of the hip joint, in maneuvering
      instruments in obese patients, and in facilitating entry to the hip joint in
      patients with spurs on the anterolateral aspect of the acetabulum. The patient is
      placed in the lateral decubitus position with the hip on which the surgery is
      being performed on the top. The leg is placed in traction and a well-padded
      perineal post is applied for countertraction. An image intensifier is placed
      around the hip to help direct the instruments into the hip joint. Traction is
      necessary to reach the depths of the hip joint. After traction is applied, two
      portals are made over the greater trochanter and one directly anterior to the
      greater trochanter. A capsulotomy is performed at each portal site to maintain
      the portals and to aid in maneuvering the arthroscope and instruments. Traction
      is released and the hip is flexed to allow visualization of the intracapsular
      area around the femoral neck. An additional, ancillary portal (made anterior and
      distal to the first direct anterior portal) may be required to reach the
      intracapsular portion around the femoral neck. A regular traction table requires
      adjustments of the perineal and traction posts to apply traction to the leg of a
      patient in the lateral decubitus position. Special traction devices make setup
      easier. The lateral approach to hip arthroscopy provides a safe and consistent
      method of entering, visualizing, and performing surgical procedures on the hip.

PMID- 16958468
TI  - Hip arthroscopy by the supine approach.
AB  - The supine approach to arthroscopy of the hip has been well described, and the
      safe zones for arthroscopy and the technique of precise portal placement
      necessary for optimal access have been well established. However, with a growing
      understanding of hip pathology and its etiology, additional methods have been
      devised to address this pathology. Thus, the technique of hip arthroscopy
      continues to evolve, including incorporation of the peripheral compartment
      evaluation as part of the routine procedure.

PMID- 16958469
TI  - Arthroscopic treatment of femoroacetabular impingement: a proposed technique with
      clinical experience.
AB  - Femoroacetabular impingement is a condition that primarily occurs in young and
      middle-aged adults. It is characterized by hip pain felt mostly in the groin.
      Radiographs often appear normal to the untrained observer; however, on careful
      analysis an anterior to lateral bump may be seen at the head-neck junction as an
      extension of the physeal line. An effective open technique using a safe surgical
      dislocation of the hip has been developed to alleviate femoroacetabular
      impingement. An arthroscopic equivalent of the open technique has been developed.
      Early results are favorable and may be comparable to those achieved with the open
      technique.

PMID- 16958470
TI  - Evaluation and management of the snapping iliopsoas tendon.
AB  - Snapping caused by the iliopsoas tendon ("internal coxa saltans") is a common
      incidental observation that often requires little treatment on the part of the
      clinician other than assurance to the patient that this finding is not a
      harbinger of future problems. Most symptomatic patients can be managed with a
      properly structured conservative treatment program. However, surgical
      intervention may be indicated for select recalcitrant painful snapping that is
      unresponsive to conservative treatment. Traditional literature has proposed open
      procedures with relaxation or release of the tendinous portion of the iliopsoas.
      Recent experience with endoscopic release of the iliopsoas has met with favorable
      results at least comparable to those reported for open techniques. An obvious
      advantage is the less invasive nature that facilitates rehabilitation and return
      to function. However, of equal importance, most patients with recalcitrant
      painful snapping of the iliopsoas tendon have been found to have associated intra
      articular pathology. The endoscopic method allows concomitant arthroscopy of the
      joint to assess and address this coexistent damage that, if overlooked, could be
      a cause of poor results. A strategy for management of painful snapping caused by
      the iliopsoas tendon is detailed, including the technique for endoscopic release.

PMID- 16958471
TI  - Physiologic effects of intramedullary reaming.
AB  - Reaming has a significant biologic and mechanical impact on the physiology of
      fracture healing. A review of the thermal, pulmonary, and osteogenic effects of
      reaming can provide evidence-based guidelines to assist the clinician in
      improving patient outcomes. Thermal necrosis is a rare but commonly referenced
      complication of reaming. The risks of heat-induced cortical damage can be
      minimized by sequential reaming with sharp instruments and by reaming with
      instruments that are sized appropriately to fit the intramedullary canal. The use
      of a tourniquet while reaming does not increase the risk of thermal necrosis.
      Reaming results in increased intramedullary pressure and secondary embolization
      of marrow elements to the pulmonary system. The clinical significance of these
      embolic events remains controversial. Potential complications can be reduced by
      using reamer designs and techniques that minimize the increases in intramedullary
      pressure. Outcome studies consistently show that reaming potentiates the healing
      response with intramedullary fixation of long-bone fractures. Recent laboratory
      studies implicate alterations in cortical blood flow patterns and the osteogenic
      potential of reaming debris as critical components of this process.

PMID- 16958472
TI  - High-energy proximal tibial fractures: treatment options and decision making.
AB  - High-energy proximal tibial fractures are complex injuries with significant
      associated soft-tissue damage. There is a high percentage of open injuries,
      compartment syndrome, and vascular injuries in patients with these fractures.
      These patients usually have significant articular depression, excessive
      comminution, condylar displacement, and metadiaphyseal extension of the fracture.
      Management of these complex injuries requires treatment of the soft tissues and
      bony components. Surgical treatment of these injuries traditionally has been
      associated with substantial complications such as infection, knee stiffness,
      malunion, loss of fixation, soft-tissue failure, and amputations. Staged
      treatment, with initial application of a spanning external fixator followed by
      definitive fixation, has been used in recent years to decrease the risk and rate
      of complications. Definitive fixation may be performed using traditional open
      approaches or percutaneously or an external fixator may be used. Development of a
      protocol for treating these injuries must be done to allow optimal fracture and
      patient outcomes.

PMID- 16958473
TI  - Locked plates for proximal tibial fractures.
AB  - Proximal tibial fractures are complex and serious injuries that can result from
      direct high-energy trauma or indirect low-energy trauma. Many injuries involve
      the articular surface, and because of their proximity to the knee joint,
      deforming forces can create instability and malalignment. Furthermore, accessing
      the articular surface and fracture site can further compromise already precarious
      soft-tissue injuries. Treatment of these injuries is challenging, and treatment
      options can be controversial.

PMID- 16958474
TI  - Delayed unions of the tibia.
AB  - Delayed union of the tibia represents a diverse group of clinical problems that
      can at times be challenging for even the most experienced surgeon to treat. Early
      recognition and treatment can help patients avoid prolonged periods of pain and
      disability. Many factors have been associated with delayed union or nonunion;
      most of these factors are dictated by the injury and patient factors but others
      are within the surgeon's control. Although high rates of union are obtained in
      many series of tibial fractures using simple treatment methods, nonunion is seen
      by all practitioners treating tibial fractures. Early intervention to prevent
      nonunion seems to be in the best interest of patients and surgeons. Treatment
      must take into account the biologic and mechanical factors contributing to delay
      in fracture union.

PMID- 16958475
TI  - Component alignment in total knee arthroplasty.
AB  - Prosthetic component positioning in total knee arthroplasty is a critical
      determinant of long-term survival of the implant. The goal of component alignment
      is to recreate the normal mechanical axis of the lower extremity and to achieve a
      stable, balanced articulation. In addition to component position, it is desirable
      to select a prosthesis size that, as closely as possible, matches that of the
      patient. The tibial component is usually placed perpendicular to the longitudinal
      axis of the tibia in the coronal plane and, depending on implant design, sloped
      neutral to posteriorly in the sagittal plane. This positioning differs from the
      normal alignment of the tibial articular surface, which is oriented in slight
      varus. Because of the change in tibial orientation, the desired femoral component
      position also differs slightly from the normal anatomic configuration.

PMID- 16958476
TI  - Soft-tissue balancing in primary total knee arthroplasty.
AB  - The surgical goal of primary total knee arthroplasty (TKA) is to provide a well
      balanced soft-tissue envelope surrounding a well-aligned, well-fixed implant.
      Some knee surgeons have emphasized that a good outcome in primary TKA is more
      dependent on soft-tissue management than bone management. Thus, it is imperative
      that the surgeon is familiar with knee soft-tissue balancing techniques to
      address the varus, valgus, and associated flexion contracture deformities
      commonly encountered in primary TKA.

PMID- 16958477
TI  - Posterior cruciate ligament-retaining, posterior stabilized, and varus/valgus
      posterior stabilized constrained articulations in total knee arthroplasty.
AB  - The degree of constraint required to achieve immediate and long-term stability in
      total knee arthroplasty (TKA) is frequently debated, with most authors favoring
      the least degree of constraint possible. There are generally three surgical
      biases in TKA involving the posterior cruciate ligament (PCL): surgeons who
      always retain the PCL, those who always sacrifice it, and those who decide to
      retain or sacrifice the PCL based on pathology. Surgeons who retain the PCL argue
      that it is one of the strongest ligaments about the knee and affords inherent
      stability to the TKA, whereas the proponents of PCL sacrifice argue that the PCL
      is compromised as a result of the degenerative process. With the pathologic
      approach, the diseased state of the knee at the time of arthroplasty dictates
      whether the PCL is retained or sacrificed. In patients without significant varus
      or valgus malalignment and without significant flexion, contracture may be
      addressed by retaining the PCL, whereas the PCL should be removed in patients
      with these deformities. Certain disease processes are more amendable to PCL
      sacrifice, such as end-stage degenerative joint disease secondary to rheumatoid
      arthritis, previous patellectomy, previous high tibial osteotomy or distal
      femoral osteotomy, and posttraumatic arthritis with disruption of the PCL. The
      degree of constraint of the articulation in TKA should be dictated by the degree
      of disease and associated deformity. A pathologic approach is rational and has
      clinically based evidence of success. Surgeons should have the option of
      modifying the degree of constraint at the time of surgical intervention.
      Currently, many TKA implant systems offer such flexibility.

PMID- 16958478
TI  - Cemented and cementless fixation: results and techniques.
AB  - There are multiple reports of successful cemented and cementless total knee
      arthroplasty in the current literature. Although technically more demanding to
      implant, selected cementless designs, with nearly 20 years of follow-up,
      demonstrate near-equal success compared with cemented implants, the gold
      standard. Far more important than the decision to use a cemented or cementless
      implant is the use of precise technique, adequate balancing of the soft tissues,
      and proper overall alignment. Failure to achieve these basic principles can lead
      to early failure in any total knee replacement system.

PMID- 16958479
TI  - Patellar tracking in primary total knee arthroplasty.
AB  - The patellofemoral articulation has been frequently overlooked as a significant
      contributor to the success of primary total knee arthroplasty. Neglecting the
      patellofemoral articulation frequently leads to abnormal patellofemoral tracking.
      To understand the concept of patellofemoral maltracking, the importance of the Q
      angle, mechanical alignment, femoral component rotation, tibial component
      positioning, patellar component positioning, patellar height, and patellar
      resurfacing as factors related to patellofemoral tracking and function must be
      considered. Greater attention to and understanding of these factors will lead to
      significant pain relief and overall patient satisfaction.

PMID- 16958480
TI  - Management of infection at the site of a total knee arthroplasty.
AB  - Infection following total knee arthroplasty remains a major complication in joint
      reconstruction, resulting in significant morbidity to the patient and increased
      hospital costs. The diagnosis of infection is often made based on clinical
      criteria, although adjunctive measures including blood work, plain radiographs,
      and arthrocentesis are often helpful in confirming the diagnosis and planning
      subsequent treatment. For patients in whom the diagnosis of infection cannot be
      immediately confirmed, an acute intraoperative tissue analysis by a skilled
      pathologist and experienced surgeon is required. Treatment of this complication
      is directed by the chronicity of the infection, stability of the components, and
      medical status of the patient. Although debridement with component retention may
      be successful in the acute postoperative stage of joint replacement, a two-staged
      revision with removal of all components followed by an adequate course of
      parenteral antibiotics prior to reimplantation remains the gold standard for
      eradicating chronic infection. The addition of antibiotic-impregnated cement
      spacers (static or articulating) has also been implicated as a useful adjunct to
      treatment. Long-term suppressive antibiotic treatment, arthrodesis, resection
      arthroplasty, and amputation are reserved for specific clinical situations in
      which a staged revision or debridement are unlikely to yield favorable results.

PMID- 16958481
TI  - Complications of anterior cruciate ligament reconstruction.
AB  - Injury to the anterior cruciate ligament (ACL) can result in recurrent
      instability, impairment, and progressive joint damage in athletes who return to
      high-risk sports activities. ACL reconstruction often is indicated. With
      refinement of surgical techniques and accelerated rehabilitation, the number of
      complications following ACL reconstruction has greatly decreased since the 1980s.
      Nevertheless, ACL reconstruction remains a complex procedure with multiple steps
      and many possible complications. Understanding the incidence and etiology of the
      more common complications associated with ACL reconstruction during the
      preoperative and postoperative periods is important to manage (if not avoid) the
      risk of these complications.

PMID- 16958482
TI  - Avoidance and management of intra-articular complications of anterior cruciate
      ligament reconstruction.
AB  - An estimated 70,000 to 100,000 anterior cruciate ligament reconstructions are
      performed each year in the United States. With the increasing number of anterior
      cruciate ligament surgeries being performed, a concomitant increase in
      intraoperative complications can be expected. Complications include those
      associated with tunnel placement, notchplasty, graft fixation and advancement,
      suture laceration, graft laceration, guidewire insertion and removal, intra
      articular hardware, posterior cruciate ligament laceration, compartment syndrome,
      and vascular injury.

PMID- 16958483
TI  - Complications of anterior cruciate ligament reconstruction: graft issues.
AB  - Anterior cruciate ligament reconstruction has become one of the most common
      arthroscopic procedures performed on the knee. Complications from this
      reconstructive surgery, although uncommon, can be devastating to the overall
      function of the knee. Several strategies exist to avoid potential complications
      related specifically to graft harvest and implantation, and to complications
      related to the bone-patellar tendon-bone and hamstring autografts, and patellar
      tendon allograft, the most common grafts currently used.

PMID- 16958484
TI  - Single-bundle versus double-bundle posterior cruciate ligament reconstruction:
      scientific rationale and surgical technique.
AB  - Despite many recent advances in the understanding of the posterior cruciate
      ligament (PCL) and its function, the optimal treatment of PCL injuries remains
      controversial. Although it now is well known that the PCL is made up of two
      distinct bundles, each of which plays a vital role in achieving knee stability,
      questions abound regarding the need for double-bundle reconstruction rather than
      single-bundle techniques. Currently, the reconstruction technique is selected
      based on the injury pattern. In acute (< 3 weeks from the time of injury)
      combined PCL injuries (PCL/posterolateral corner, PCL/medial collateral ligament,
      and knee dislocations), a single-bundle reconstruction designed to replicate the
      anatomy of the anterolateral bundle is used. In acute or chronic PCL injuries in
      which both the posteromedial bundle of the PCL and the meniscofemoral ligaments
      remain intact, a single-bundle augmentation is used. A double-bundle
      reconstruction is performed when all three components of the PCL complex
      (anterolateral band, posteromedial band, and meniscofemoral ligaments) have been
      ruptured. These patterns are generally chronic, with severe knee laxity following
      a previous traumatic injury (PCL/posterolateral corner or knee dislocation).
      Tailoring the PCL reconstruction technique to the individual injury pattern will
      likely yield a reconstruction that better replicates the natural biomechanics of
      the native knee, thereby resulting in better functional outcomes.

PMID- 16958485
TI  - Two-strand posterior cruciate ligament reconstruction with a quadriceps tendon
      patellar bone autograft: technical considerations and clinical results.
AB  - In patients with complete posterior cruciate ligament (PCL) ruptures in which 10
      mm or more of increased posterior tibial translation is detected, associated knee
      disorders must be treated at the same time as the PCL injury. Varus malalignment
      and any abnormal medial or lateral ligament deficiency must be corrected before
      or with PCL reconstruction to avoid the risk of failure of the PCL graft. Gait
      retraining is recommended for patients with abnormal knee hyperextension patterns
      before ligament reconstruction is performed. Advances in PCL reconstruction
      include the use of a two-strand graft that may be placed using either a tibial
      inlay or an all-arthroscopic tibial tunnel technique. Biomechanical studies have
      shown a reduction in graft tension and improved load sharing in these constructs
      compared with single-strand reconstructions. The tibial inlay method can be used
      in athletic patients, and it also is required in PCL revisions in which a prior
      tibial tunnel must be avoided to achieve graft fixation. The tibial tunnel
      technique is used to treat dislocated knees for which reconstruction of multiple
      knee ligaments is required or when prior arterial injury or posterior skin or
      muscle damage limits the indications for a posterior open approach. Postoperative
      rehabilitation should protect the PCL graft from high forces and repetitive
      cyclic knee motions during the first 4 weeks postoperatively.

PMID- 16958486
TI  - Arthrodesis techniques in the management of stage II and III acquired adult
      flatfoot deformity.
AB  - The proper management of acquired flatfoot deformity requires obtaining a careful
      patient history and physical examination of the foot, ankle, and lower extremity.
      Accurate assessment of foot flexibility and localization of pain will aid in
      decision making. Nonsurgical management may not be successful in patients with
      advanced disease, particularly with the development of degenerative changes.
      Surgical management of advanced acquired adult flatfoot deformity (stages III and
      IV) is indicated with failure of nonsurgical management and consists primarily of
      arthrodesis for the foot component of the deformity. The foot component may
      include the subtalar, talonavicular, calcaneocuboid, or tibiotalar joints, or a
      combination of these joints. Adjunctive procedures, such as Achilles tendon
      lengthening, medial displacement calcaneal osteotomy, lateral column lengthening,
      and plantar flexion osteotomy of the first ray are useful in correcting residual
      deformities after hindfoot realignment. Proper selection of surgical procedures
      will maximize the potential for a good outcome. It is critical to correct all
      components of the deformity simultaneously in order to minimize recurrence of the
      deformity.

PMID- 16958487
TI  - Hindfoot endoscopy for posterior ankle pain.
AB  - Hindfoot pain can be caused by a variety of pathologies, most of which can be
      diagnosed and treated with endoscopy. The main indications are posterior tibial
      tenosynovectomy, diagnosis of a longitudinal peroneus brevis rupture, peroneal
      tendon adhesiolysis, flexor hallucis longus release, os trigonum removal,
      endoscopic treatment of retrocalcaneal bursitis, endoscopic treatment of Achilles
      (peri)tendinopathy, and treatment of ankle joint or subtalar joint pathology. The
      advantages of endoscopic hindfoot surgery over open surgery are less morbidity,
      reduction of postoperative pain, outpatient treatment, and functional
      postoperative treatment. Optimal portal placement for each indication has been
      identified in a cadaver study. The approach for the flexor hallucis longus and os
      trigonum is particularly challenging because of the adjacent neurovascular
      bundle. A two-portal hindfoot approach with the patient in the prone position
      offers excellent access to the flexor hallucis longus. The posterior ankle
      compartment, os trigonum, and subtalar joint can be visualized and treated
      through this approach. In 240 consecutive procedures, no major complications were
      reported. The two-portal hindfoot endoscopy approach is a safe, reliable, and
      exciting method to diagnose and treat a variety of posterior ankle problems.
      Endoscopic calcaneoplasty for retrocalcaneal bursitis offers a good alternative
      to open resection. Experienced arthroscopic surgeons will find this technique
      rewarding.

PMID- 16958488
TI  - Arthroscopy of the subtalar joint and arthroscopic subtalar arthrodesis.
AB  - Subtalar arthroscopy has become a valuable adjunct to the tools used in lower
      extremity surgery. For the past 25 years, ankle arthroscopy has been in vogue for
      treating a variety of conditions. Subtalar arthroscopy has more treatment
      limitations and is more technically difficult to perform than ankle arthroscopy
      because of the anatomic confines and structure of the subtalar joint. Most
      procedures are performed on the posterior aspect of the subtalar joint. The
      subtalar joint is composed of three articulations (posterior, middle, and
      anterior facets) and is surrounded by a variety of intra-articular and extra
      articular ligaments, whose anatomy must be fully understood before attempting
      this procedure. Subtalar arthroscopy may be indicated for diagnostic purposes and
      for debridement of synovial impingement syndromes in the sinus tarsi. It may be
      used to examine loose bodies or osteochondral lesions, to address fractures of
      the lateral process of the talus, and to evaluate subtalar instability to
      determine appropriate stabilization methods. Arthroscopic subtalar arthrodesis
      also has gained credibility over the past 10 years as an acceptable surgical
      procedure. Arthroscopic evaluation of subtalar instability is useful in planning
      the appropriate stabilization. Subtalar arthroscopy is usually performed with the
      patient in the lateral decubitus position without traction. Anterior and
      posterior portals as well as an accessory anterior portal are usually necessary
      to perform all of the above procedures. Because of the limited confines of the
      joint, care must be taken to prevent any articular cartilage damage. When
      performing subtalar arthroscopy in conjunction with ankle arthroscopy, the
      subtalar arthroscopy should be performed first to avoid excessive extravasation
      from the ankle arthroscopy, which could obscure entry to the subtalar joint.
      Complications of subtalar arthroscopy are similar to those encountered in ankle
      arthroscopy, such as damage to the sural and superficial peroneal nerves.

PMID- 16958489
TI  - Causes of sagittal spinal imbalance and assessment of the extent of needed
      correction.
AB  - Most patients with spinal sagittal imbalance have a fusion mass that is either
      kyphotic or hypolordotic, with segments above or below the fusion that have
      subsequently degenerated. The four most common presentations include a patient
      who had a long fusion for adolescent idiopathic scoliosis with subsequent
      degeneration distally; a patient with degenerative sagittal imbalance in whom
      fusions have initially been performed in the distal lumbar spine in a somewhat
      hypolordotic or kyphotic position with subsequent degeneration of segments above
      the fusion; a patient with posttraumatic kyphosis; and a patient with ankylosing
      spondylitis. The surgical solutions usually involve a combination of osteotomies
      through the fusion mass and extension of the fusion to include degenerated
      segments. Most of the correction is accomplished by the osteotomies with
      additional correction achieved by adding the degenerated segments to the fusion
      in patients with idiopathic scoliosis, degenerative sagittal imbalance, or
      posttraumatic kyphosis. For patients with ankylosing spondylitis, the correction
      is achieved entirely with osteotomies. The usual goal is to normalize the
      regional segmental spinal alignment as much as possible and to achieve global
      balance. Global balance is confirmed when the C7 plumb falls over the lumbosacral
      disk on a standing long cassette lateral radiograph taken with the patient
      standing with knees fully extended in a natural, comfortable position. Most
      patients should have at least 10 degrees to 20 degrees more lumbar lordosis than
      thoracic kyphosis. Usually a Smith-Petersen osteotomy will achieve 10 degrees of
      correction and a pedicle subtraction osteotomy will produce 30 degrees to 35
      degrees of lordization of the spine.

PMID- 16958490
TI  - Smith-Petersen osteotomy of the spine.
AB  - The Smith-Petersen osteotomy has been a mainstay in the treatment of sagittal
      deformity since it was first described in 1945. The primary indication for an
      osteotomy is fixed sagittal deformity. When an osteotomy is performed in a
      patient with ankylosing spondylitis, it can be combined with an anterior column
      osteoclasis to achieve a correction of up to 40 degrees to 50 degrees. When
      performed for other indications, the osteotomy can result in approximately 10
      degrees of correction per level treated.

PMID- 16958491
TI  - Role and technique of eggshell osteotomies and vertebral column resections in the
      treatment of fixed sagittal imbalance.
AB  - Fixed sagittal imbalance of the spine leads to a disabling posture with
      compensatory hip and knee flexion. The most common causes of fixed sagittal
      imbalance include degenerative lumbar disease, complications from the use of
      distraction instrumentation in the lower lumbar spine, ankylosing spondylitis,
      and posttraumatic kyphosis. Surgical procedures to correct sagittal deformities
      include the posterior Smith-Petersen osteotomy, pedicle subtraction osteotomy,
      and posterior vertebral column resection. For complex multiplanar deformities,
      combined anterior and posterior vertebral column resection may be needed to
      provide vertebral column shortening and balanced correction in the coronal and
      sagittal planes. Current reports of these procedures stress the importance of
      patient selection, radiographic evaluation, and meticulous surgical technique.
      Complications include excessive blood loss, incomplete correction, wound
      infection, and pseudarthrosis. Most patients who are treated with these
      procedures report a high level of satisfaction with the outcome.

PMID- 16958492
TI  - Image guidance in spinal surgery.
AB  - Image guidance is a rapidly developing surgical technology that allows
      intraoperative navigation of surgical instruments relative to imaging studies.
      This technology has the potential to increase the safety, accuracy, and
      efficiency of certain procedures in spinal surgery. Currently the procedures most
      applicable to the use of image guidance techniques include the placement of
      spinal implants, minimal access spinal surgery techniques, and complex
      osteotomies and spinal arthroplasty. Several types of image guidance systems are
      currently available, each with certain advantages and disadvantages that must be
      understood by the operating surgeon. In the future, it is likely that the use of
      image guidance technology will increase in the field of spinal surgery as image
      guidance systems become more efficient and less expensive.

PMID- 16958493
TI  - Gene therapy and tissue engineering in orthopaedic surgery.
AB  - Despite setbacks in other fields, gene therapy in orthopaedic surgery continues
      to serve as the basis for novel treatments of various musculoskeletal disorders.
      Even in the brief time since the last review of scientific progress in this area,
      another orthopaedic-related disease has joined the ranks of those studied in gene
      therapy clinical trials. Armed with new techniques and new reagents, and
      committed to the increased use of tissue engineering, physicians and scientists
      continue to work together to accelerate tissue repair and reverse the course of
      chronic debilitating diseases.

PMID- 16958494
TI  - Pearls and pitfalls in the evaluation of pediatric congenital and developmental
      disorders.
AB  - Orthopaedic surgeons who treat children should have a thorough understanding of
      pediatric congenital and developmental disorders. It is paramount to develop
      approaches to these disorders that minimize risks to the patient and lessen the
      possibility of litigation against the treating physician. It is important to be
      aware of safe and effective approaches to specific conditions that highlight
      pearls and potential pitfalls of treatment.

PMID- 16958495
TI  - Treatment of a recurrent clubfoot deformity after initial correction with the
      Ponseti technique.
AB  - Early recognition and appropriate treatment of recurrent deformity (relapse) is
      an important component of the Ponseti technique of clubfoot correction. After
      correction of a clubfoot deformity by the Ponseti technique, relapse usually
      involves equinus and varus of the hindfoot. Cavus and adductus rarely recur to a
      clinically significant degree. Clubfoot recurs most frequently and quickly while
      the foot is rapidly growing-during the first several years of life. Recurrence of
      deformity will almost always occur, even after complete correction with the
      Ponseti technique, if appropriate bracing is not used. Treatment of clubfoot
      relapse in infants and toddlers is identical to the original correction maneuver.
      In a patient approximately 2.5 years of age, a relapse can be treated with
      anterior tibial tendon transfer to the third cuneiform with or without Achilles
      tendon lengthening. The indication for anterior tibial tendon transfer is the
      presence of dynamic supination during gait. After tendon transfer, bracing is no
      longer required because the eversion force of the transferred tendon maintains
      the correction. In a long-term follow-up study of patients treated by the Ponseti
      technique, the necessity for anterior tibial tendon transfer did not compromise
      the outcome with respect to level of pain and functional limitations. Because
      anterior tibial tendon transfer is joint sparing, the foot retains maximal
      strength and suppleness. Good long-term results can be anticipated despite
      clubfoot relapse.

PMID- 16958496
TI  - Injury of the cervical spine in young children.
AB  - The evaluation of injury of the cervical spine in children is complicated by
      biomechanics of the pediatric cervical spine that differ from those in the adult,
      by incomplete maturation and ossification of the vertebral segments, and by
      difficulties the physician may have in communicating with the child. Because the
      upper cervical region, from occiput to C2, is most susceptible to injury in
      children, it is important to have an understanding of mechanisms of injury,
      diagnostic imaging modalities, and therapeutic interventions. A clear
      understanding of adult and pediatric cervical spine differences will facilitate
      early diagnosis and appropriate treatment of cervical spine injuries in young
      children.

PMID- 16958497
TI  - Cervical spine injuries in the pediatric and adolescent athlete.
AB  - Injuries of the cervical spine in the pediatric and adolescent athlete are less
      common than other musculoskeletal injuries. Although many of these injuries are
      relatively minor, serious and potentially unstable or progressive spinal injury
      must be excluded. Important anatomic differences between the child younger than
      10 years and older children and adolescents influence the types of injuries
      sustained and make assessment of the child's cervical spine sometimes difficult
      for practitioners accustomed to treating adolescent and adult athletes. Stable
      soft-tissue injuries of the cervical spine are the most common injuries that
      occur in all athletes. These injuries are responsive to symptomatic treatment and
      aggressive rehabilitation. Stingers are injuries of the brachial plexus and upper
      cervical roots that result from stretching or compressive forces associated with
      collision sports. Rapid return of sensory and motor dysfunction of a single upper
      extremity characterizes this entity; long-term disability is rare. Cervical cord
      neurapraxia (CCN) with transient quadriplegia is most commonly seen in football
      players. Most athletes fully recover. Cervical canal stenosis as defined by a
      Pavlov/Torg ratio of less than or equal to 0.8 is predictive of recurrent CCN.
      Young athletes sustain CCN secondary to hypermobility of the immature cervical
      spine. Return to play after these injuries is controversial. The athlete with
      Down syndrome and potential cervical hypermobility requires a careful cervical
      and neurologic evaluation prior to clearance for participation in sports.

PMID- 16958498
TI  - Torticollis in infants and children: common and unusual causes.
AB  - Torticollis is a clinical symptom and sign characterized by a lateral head tilt
      and chin rotation toward the side opposite to the tilt. Many conditions cause
      torticollis. The differential diagnosis is different for infants than for
      children and adolescents. Congenital muscular torticollis associated with a
      contracture of the sternocleidomastoid muscle is the most common etiology of
      torticollis in infants. The condition of most infants with congenital muscular
      torticollis improves with a regimen of manual cervical stretching. Congenital
      anomalies of the occipital condyles and upper cervical spine must be ruled out
      before performing a release of the sternocleidomastoid muscle in a child who
      fails to improve with physical therapy. Unusual nonmuscular causes of torticollis
      in the infant also must be considered and include ocular torticollis caused by
      eye muscle weakness, Sandifer's syndrome resulting from gastroesophageal reflux,
      neural axis abnormalities, and benign paroxysmal torticollis. Torticollis in the
      older child is most frequently a manifestation of atlantoaxial rotatory
      displacement resulting from trauma or oropharyngeal inflammation (Grisel's
      syndrome). Retropharyngeal abscesses and pyogenic cervical spondylitis are
      unusual infectious causes of torticollis. Intermittent torticollis associated
      with headaches, vomiting, or neurologic symptoms may be caused by tumors of the
      posterior fossa. Benign and malignant neoplasms of the upper cervical spine are
      rare causes of torticollis in children. Torticollis resulting from cervical
      dystonia is also rare in children but may be seen in older adolescents.

PMID- 16958499
TI  - Infections and inflammatory conditions of the cervical spine in children.
AB  - Because infections and inflammatory disorders of the cervical spine are uncommon
      in children and adolescents, diagnosis and treatment are frequently delayed.
      Intractable pain, limitation of neck motion, and neurologic compromise may occur
      as the result of these pathologic processes. It is important to identify these
      symptoms for early diagnosis and treatment of conditions such as bacterial and
      tuberculous infections, intervertebral disk calcification, juvenile rheumatoid
      arthritis, and Grisel's syndrome.

PMID- 16958500
TI  - Managing the academic orthopaedic practice as a business.
AB  - Efforts by academic orthopaedic surgeons to provide patient care, educate
      trainees, and perform research into the various facets of musculoskeletal
      afflictions are being challenged by changes in technology, financing, and
      demographics. In the current economy, efficient, cost-effective management is
      essential for survival of an academic or private orthopaedic practice. All
      practitioners should be acutely aware of the principles involved in the
      management of a private practice, but academic practices must also deal with such
      factors as the teaching of residents and medical students, the expectation of
      comprehensive coverage, indigent case load, and research. Orthopaedic surgeons in
      the academic environment must proactively manage their practices as businesses to
      maintain sufficient financial viability to support the other endeavors.
      Academicians therefore must have an understanding of the principles that will
      impact their practice and assist in the analysis of an academic practice's
      productivity.

PMID- 16958501
TI  - Emergency preparedness: things to consider before the game starts.
AB  - Emergency preparedness for athletic events is essential. A written emergency plan
      should include a list of the members of the medical team; the responsibilities of
      each person on the team; and the means of communication between those persons,
      including the emergency medical technicians covering athletic events, the staff
      at the hospital to which injured athletes will be transported, and the members of
      the athletic department. Prior to any competition, the medical person in charge
      should be certain all needed response equipment is available, assess the safety
      of the playing field and the players' protective equipment, and ensure that
      adequate fluids are available for consumption during the competition. In
      addition, the medical cards of each athlete should be reviewed; weather reports
      should be checked for inclement weather; and the availability of a working phone
      should be verified. Being prepared, before practice or competition begins,
      ensures that prompt appropriate care will be provided for injured or ill
      athletes.

PMID- 16958502
TI  - Care of the high school athlete: prevention and treatment of medical emergencies.
AB  - An important duty of any sports medicine physician is the care of athletes on the
      field and at the sidelines. Orthopaedic surgeons, who are trained to treat most
      musculoskeletal injuries, may not be as well prepared to treat the variety of
      medical issues and emergencies that are encountered in the "on-the-field"
      setting. In treating adolescent and high school athletes, advance preparation by
      the physician is critical for such entities as exercise-induced asthma,
      anaphylaxis, certain cardiac conditions, seizures, diabetes, and heat illnesses.
      The initial approach to the athlete who "goes to ground" always remains the same-
      management of the airway (with cervical spine precautions); establishment and
      maintenance of breathing and circulation; a limited neurologic examination to
      assess function; and removal of the athlete from the hazardous environment.
      Additional treatment is dictated by the specific illness or injury. As is usually
      the case, prevention is the best form of treatment. Many conditions can be
      detected at the preparticipation physical examination, which includes a thorough
      history and focused physical examination. Specific cardiovascular conditions that
      may be screened for include hypertrophic cardiomyopathy, Marfan syndrome, some
      congenital coronary artery abnormalities, and electrophysiologic rhythm
      disturbances. This examination also offers one of the best opportunities to
      provide information to athletes regarding optimal management of any chronic
      medical diseases. In preparation for an athletic event, excessive environmental
      heat and humidity may be addressed with several preventive strategies. Physicians
      also may be asked to provide counseling and make decisions about return to play
      for athletes who have had certain infectious diseases, including upper and lower
      respiratory infections and infectious mononucleosis.

PMID- 16958503
TI  - Concussions in adolescent athletes.
AB  - A concussion is defined as a complex pathophysiologic process affecting the brain
      that is induced by traumatic biomechanical forces. Concussions are caused by a
      direct or indirect blow that leads to a graded set of syndromes characterized by
      functional rather than structural disturbances to the brain. Concussions are
      characterized by a wide variety of presenting symptoms, including loss of
      consciousness, amnesia, confusion, headache, and nausea. Concussions occur in
      patients participating in all levels of athletic activities, with most occurring
      in younger athletes. The evaluation of a patient with a concussion should include
      assessment of the airway, breathing, circulation, level of consciousness,
      orientation, memory, concentration, and neurologic function. Multiple grading
      scales and return to play guidelines have been published to assist the clinician
      in the treatment of patients with concussions. Diagnostic and treatment concerns
      include spinal cord injury, intracranial pathology, second impact syndrome, and
      long-term impairment of cognitive function. Computerized neuropsychologic testing
      is a new tool in the treatment of concussions. These tests measure memory, new
      learning, attention, and reaction time and should be used as an adjunct to other
      tools for clinical decision making. Published guidelines will assist in treatment
      decisions; however, it should be kept in mind that all concussions are unique
      injuries.

PMID- 16958504
TI  - "Stingers" in adolescent athletes.
AB  - Brachial plexus injuries commonly occur in athletes participating in contact
      sports. The incidence of transitory brachial plexus injury is approximately 30%
      to 50% over the course of a high school, college, or professional football
      player's career. These injuries are called "stingers" or "burners" because of the
      associated tingling that occurs in the upper extremity after the injury. Brachial
      plexus injuries are poorly understood and sometimes are difficult to manage.
      Appropriate knowledge and understanding of these injuries along with prompt
      recognition, diagnosis, and treatment are essential for optimal care of the
      injured athlete and for the athlete's timely return to play. Most injuries occur
      by one of three mechanisms: traction, compression, or hyperextension and
      compression. Injuries are clinically classified as neurapraxia,
      neurapraxia/axonotmesis, and neurotmesis according to their symptomatology and
      the pattern of symptom resolution. Most injuries are either a neurapraxia or a
      neurapraxia/axonotmesis. Most athletes recover completely and can return to play
      after they are asymptomatic and have regained full sensation, strength, and range
      of motion. Protective equipment has been introduced to decrease the occurrence of
      stingers. Education of the athlete, the family, and coaches is important to help
      them to understand and to assist in managing these injuries.

PMID- 16958505
TI  - Comprehensive study of okaspirodiol: characterization, total synthesis, and
      biosynthesis of a new metabolite from Streptomyces.
AB  - The new spiro[4.5]acetal okaspirodiol (4) was isolated from Streptomyces sp. Go
      TS 19 as a secondary metabolite in yields up to 380 mg/L. The structure of this
      cryptic ketotetrol was elucidated by different methods including X-ray analysis,
      and its equilibration under mildly acidic conditions furnishing three additional
      isomers was thoroughly studied. Although metabolite 4 is not the
      thermodynamically favored isomer, a high-yielding total synthesis was
      accomplished comprising a stereoselective spiroacetalization under equilibrium
      conditions. This approach benefits from the important influence of an
      intramolecular hydrogen bond on the stabilization of the spiro[4.5]acetal moiety.
      The biosynthesis of 4 was investigated by feeding experiments with 13C-labeled
      precursors proving its origin from a new type of the rare mixed acetate-glycerol
      biosynthetic pathway. All results are discussed on the basis of the structural
      diversity of spiroacetals in nature and their chemical properties.

PMID- 16958506
TI  - Efficient large-scale synthesis of BILN 2061, a potent HCV protease inhibitor, by
      a convergent approach based on ring-closing metathesis.
AB  - A multistep scalable synthesis of the clinically important hepatitis C virus
      (HCV) protease inhibitor BILN 2061 (1) is described. The synthesis is highly
      convergent and consists of two amide bond formations, one etherification, and one
      ring-closing metathesis (RCM) step, using readily available building blocks 2-5.
      The optimization of each step is described at length. The main focus of the paper
      is the study of the RCM step and the description of the main problems faced when
      scaling up to pilot scale this highly powerful but very challenging synthetic
      operation. Eventually, the RCM reaction was smoothly scaled up to produce >400 kg
      of cyclized product.

PMID- 16958507
TI  - Screening for galectin-3 inhibitors from synthetic lacto-N-biose libraries using
      microscale affinity chromatography coupled to mass spectrometry.
AB  - The synthesis and screening of two beta-D-Galp-(1-3)-beta-d-GlcpN (lacto-N-biose)
      disaccharide libraries are reported. Solution-phase synthetic modifications at
      the HO-2' and NH positions were performed in an effort to enhance the affinity
      toward galectin-3, a galactose-binding protein involved in tumor metastasis,
      apoptosis, and inflammation. The libraries were screened for galectin-3 binding
      by microscale frontal affinity chromatography coupled to mass spectrometry
      (FAC/MS) allowing for rapid ranking of the different inhibitors and the
      determination of the galectin-3 binding Kd's. Compounds bearing a hydrophobic
      substituent on the NH group showed the highest affinity for the lectin. The N
      naphthoyl derivative (Kd = 10.6 microM) was the best inhibitor with a 7 times
      increased affinity as compared to the N-acetyl parent compound (Kd = 73.3
      microM).

PMID- 16958508
TI  - Substituent effects on the basicity of 3,7-diazabicyclo[3.3.1]nonanes.
AB  - Basicity constants for a series of 3,7-diazabicyclo[3.3.1]nonane derivatives in
      acetonitrile with a variation over 13 orders of magnitude have been determined
      using a spectrophotometric titration technique. An excellent correlation between
      basicity and calculated proton affinities obtained at PCM-B3LYP/6
      31+G(d)//B3LYP/6-31G(d) level was found. The results are discussed in terms of
      substituent effects and compared to (15)N NMR chemical shifts.

PMID- 16958509
TI  - Synthesis of heteroaryl imines: theoretical and experimental approach to the
      determination of the configuration of C=N double bond.
AB  - The reaction between an iminophosphorane with furan-2-carbaldehyde, thiophene-2
      carbaldehyde, furan-3-carbaldehyde, and thiophene-3-carbaldehyde at 60 degrees C
      gives the corresponding trans imines in 53-84% yields, while the same reaction at
      100 degrees C gives a mixture of the corresponding trans and cis imines. Whether
      the iminophosphorane reacted with 5-nitrofuran-2-carbaldehyde or 5-nitrothiophene
      2-carbaldehyde only the trans imines were obtained in 85-89% yields. The
      irradiation of the imines obtained from thiophene-2-carbaldehyde and thiophene-3
      carbaldehyde gave the corresponding photocyclization products. Cis/trans
      stereochemistry of the imines can be assigned simulating the UV-vis spectra. In
      the case of the imine from furan-2-carbaldehyde the computed spectra are
      characterized by an intense absorption at 361 and 357 nm respectively for the
      trans-1 and trans-2 structures. No other absorptions of comparable intensity have
      been predicted: the agreement with the experimental spectrum can be considered
      good. Furthermore, the experimental weak peaks at 280 and 270 nm can be
      associated to the computed transitions at 278 and 260 nm for the trans-1 isomer.
      Several minima of the energy surface can be assigned to the cis isomer, and they
      all present a very similar energy. The structures of the cis-1 and cis-2 isomers
      present quite coincident computed electronic spectra. In both cases, the computed
      spectrum shows two principal features. For the cis-1 structure, the first
      characteristic absorption is located at 414 nm and the second one at 284 nm. For
      the cis-2 structure, the first feature is located at 412 nm and the second one at
      286 nm. The second transition is computed somewhat more intense. The experimental
      spectrum could be the consequence of similar populations of the planar cis
      structure (cis-3) and nonplanar cis structures (cis-1, cis-2, and their
      enantiomers).

PMID- 16958510
TI  - Thermodynamic origin of the increased rate of hydrolysis of phosphate and
      phosphorothioate esters in DMSO/water mixtures.
AB  - The hydrolysis rates of the dianions of phosphate and phosphorothioate esters are
      substantially accelerated by the addition of polar aprotic solvents such as DMSO
      and acetonitrile. The activation barrier DeltaG is smaller due to a lower
      enthalpy of activation. The enthalpy of transfer of p-nitrophenyl phosphate
      (pNPP) and p-nitrophenyl phosphorothioate (pNPPT), from water to 0.6 (mol) aq
      DMSO (60 mol % water in DMSO) were measured calorimetrically. The enthalpies of
      activation for the hydrolysis reactions in the two solvents permitted the
      calculation of the enthalpy of transfer of the transition states. This transfer
      is thermodynamically favorable for both the reactants and the transition states
      but is more favorable for the transition states. In the case of pNPP, the
      enthalpy of transfer of the reactant is -23.9 kcal/mol, compared to -28.3 for the
      transition state. The difference is greater for pNPPT, where the enthalpy of
      transfer of the reactant is -23.2 kcal/mol and that for the transition state is 
      35.3. The results show that the reduced enthalpies of activation in both
      hydrolysis reactions arise not from a destabilization of the reactants in the
      mixed solvent, but from the fact that the enthalpy of transfer of the transition
      states to the mixed solvent is significantly more negative than the enthalpy of
      transfer of the reactants.

PMID- 16958511
TI  - Rational design, synthesis, and application of a new receptor for the molecular
      recognition of tricarboxylate salts in aqueous media.
AB  - A rational design of a tripodal receptor for the molecular recognition of
      tricarboxylate salts in aqueous media, based on squaramide, has been performed
      using high-level DFT calculations (RI-BP86/SVP level of theory) in solution using
      the COSMO treatment, including some preliminary ab initio calculations at the
      higher RI-MP2/TZVP level of theory, comparing the ability of squaramide to bind
      carboxylate salts with two widely used guanidinium salts. The tripodal receptor
      has been synthesized using a new methodology that has been recently reported by
      some of us, and its capability of recognizing several mono-, di-, and
      tricarboxylate salts has been studied experimentally by means of microcalorimetry
      experiments in a very high competitive media, H(2)O:EtOH 1:3. These experiments
      give enthalpic and entropic data, which are unfortunately scarce in the
      literature of molecular recognition of anions. Finally, a fluorimetric ensemble
      of the receptor with fluorescein has been found to be useful for the fluorimetric
      determination of zinc citrate in a commercial toothpaste using competition
      assays.

PMID- 16958512
TI  - Convergent approaches for the synthesis of the antitumoral peptide, Kahalalide F.
      Study of orthogonal protecting groups.
AB  - Kahalalide compounds are peptides that are isolated from a Hawaiian herbivorous
      marine species of mollusc, Elysia rufescens, and its diet, the green alga
      Bryopsis sp. Kahalalide F and its synthetic analogues are the most promising
      compounds of the Kahalalide family because they show antitumoral activity. Linear
      solid-phase syntheses of Kahalalide F have been reported. Here we describe
      several new improved synthetic routes based on convergent approaches with
      distinct orthogonal protection schemes for the preparation of Kahaladide
      analogues. These strategies allow a better control and characterization of the
      intermediates because more reactions are performed in solution.

PMID- 16958513
TI  - Solvent-induced amphiphilic molecular baskets: unimolecular reversed micelles
      with different size, shape, and flexibility.
AB  - Amphiphilic molecular baskets were obtained by attaching facially amphiphilic
      cholate groups to a covalent scaffold (calix[4]arene or 1,3,5-2,4,6
      hexasubstituted benzene). In a solvent mixture consisting of mostly a nonpolar
      solvent (i.e., CCl4) and a polar solvent (i.e., DMSO), the hydrophilic faces of
      cholates turned inward to form a reversed-micelle-like conformer whose stability
      was strongly influenced by the number of the cholates and the topology of the
      scaffold. Preferential solvation of the hydrophilic faces of cholates within the
      molecule by the polar solvent was cooperative and gave the fundamental driving
      force to the conformational change. The reversed-micelle-like conformer was most
      stable in structures that allowed multiple cholates to form a microenvironment
      that could efficiently enrich the polar solvent molecules from the bulk solvent
      mixture.

PMID- 16958514
TI  - Activation of pentafluorophenylsilanes by weak Lewis bases in reaction with
      iminium cations.
AB  - The Lewis base mediated carbon-carbon bond forming reactions between
      pentafluorophenylsilanes and iminium cations were studied theoretically and
      experimentally. The complexation of silanes with anionic Lewis bases was analyzed
      computationally using DFT methods at the B3LYP/6-31+G(d) level. The
      pentafluorophenyl group was found to exhibit a significant stabilizing effect on
      the formation of pentacoordinate silicon species, with (C6F5)3SiF and C6F5SiF3
      being the strongest Lewis acids. Comparison of geometrical isomers of trigonal
      bipyramidal siliconates R2(C6F5)SiXY- (R = Me, F, Cl; X, Y = F, Cl, ClO4)
      revealed that the heteroatoms and the C6F5 group prefer to occupy apical and
      equatorial positions, respectively. Calculations of C6F5 group transfer processes
      from silanes to N,N-dimethyliminium cation lead to the following conclusions: (1)
      when employing weak Lewis bases X- = Cl-, ClO4- as activators, R2(C6F5)SiF are
      more reactive than R2(C6F5)SiX (X = Cl, ClO4); (2) the C6F5 group is much more
      reactive in an apical position than in an equatorial position of the siliconate;
      (3) a solvent greatly increases the reaction barrier by stabilizing the
      reactants; and (4) the efficiency of C-C bond formation can be improved by
      rendering the process intramolecular. It was shown experimentally that reactions
      of (C6F5)3SiF with PhCH=NMe2+TfO- can be promoted by a series of weak Lewis
      bases, from which the chloride anion was the most effective. Even more facile was
      the reaction of N-(silyloxyethyl)iminium ion (C6F5)3SiOCH2CH2N(Me)=CHPh+TfO-,
      likely proceeding via intramolecular transfer of a C6F5 group. The optimal
      conditions for pentafluorophenylation of iminium ions involved the use of
      benzyltriethylammonium chloride in refluxing dichloroethane.

PMID- 16958515
TI  - A cyclic enamine derived from 1,2-O-isopropylidene-alpha-D-xylofuranose as a
      novel carbohydrate intermediate to achieve skeletal diversity.
AB  - The commercially available carbohydrate 1,2-O-isopropylidene-alpha-D-xylofuranose
      was efficiently transformed into the high-added-value synthetic scaffold 8. The
      transformation requires the synthesis of the 5-O-tosyl derivative 7 and its
      subsequent intramolecular cyclization under basic conditions to give the cyclic
      enamine 8. Reaction of 8 with O-, N-, S-, and C-nucleophiles and amino acids
      allowed its efficient transformation (one-step, high yields, and easy
      purifications) into fused cyclic sugar derivatives with rather unusual molecular
      skeletons in a completely regio- and stereoselective manner. The characteristics
      of the sugar derivative 8 established here, high reactivity, synthetic
      accessibility, and the potential for conversion into a vast collection of
      products by the action of different nucleophiles, indicate that it will prove to
      be a useful chiral intermediate for achieving skeletal diversity. The constrained
      structures and dense functionalization of the polycyclic sugar derivatives
      generated from 8 make these compounds promising candidates for use as starting
      agents for the production of new analogues and as drugs.

PMID- 16958516
TI  - Osmium catalyzed dihydroxylation of 1,2-dioxines: a new entry for stereoselective
      sugar synthesis.
AB  - A series of 3,6-substituted 3,6-dihydro-1,2-dioxines were dihydroxylated with
      osmium tetroxide to furnish 1,2-dioxane-4,5-diols (peroxy diols) in yields
      ranging from 33% to 98% and with de values not less than 90%. The peroxy diols
      were then reduced to generate a stereospecific tetraol core with R,R,S,S or
      "allitol" stereochemistry. The peroxy diols and their acetonide derivatives were
      also ring-opened with Co(II) salen complexes to give novel hydroxy ketones in 77
      100% yield, including the natural sugar psicose. Importantly, preliminary work on
      the catalytic asymmetric ring-opening of meso-peroxy diols using the Co(II)
      Jacobsens's catalyst indicates that asymmetric sugar synthesis from 1,2-dioxines
      is possible.

PMID- 16958517
TI  - Cytotoxic macrolides from a new species of the deep-water marine sponge
      Leiodermatium.
AB  - Chemical investigation of a new species of the deep-water marine sponge
      Leiodermatium, collected by manned submersible at a depth of 740 feet in Palau,
      resulted in the isolation of two cytotoxic macrolides, leiodolides A (1) and B
      (2). The leiodolides represent the first members of a new class of 19-membered
      ring macrolides, incorporating several unique functional groups including a
      conjugated oxazole ring, a bromine substituent, and an alpha-hydroxy-alpha-methyl
      carboxylic acid side-chain terminus. The structures of these new metabolites were
      established by spectroscopic analysis, chemical modification, and degradation.
      The relative and absolute stereochemistries at most chiral centers were assigned
      on detailed interpretation of spectroscopic data, coupled with chemical
      degradation and application of the modified Mosher ester method. Leiodolide A
      showed significant cytotoxicity (average GI(50) = 2.0 microM) in the National
      Cancer Institute's 60 cell line panel with enhanced activity against HL-60
      leukemia and OVCAR-3 ovarian cancer cell lines.

PMID- 16958518
TI  - Effects of conformation on the stereochemistry of solvent attack on benzylic beta
      hydroxycarbocations: mechanisms of epoxide hydrolysis reactions.
AB  - The rates and products from the acid-catalyzed and the pH-independent reactions
      of two diastereomeric 6-methoxy-trans-1,2,3,4,4a,10a-hexahydrophenanthrene 9,10
      oxides (5b and 7b), along with their cis and trans chlorohydrins, have been
      determined in dioxane/water solutions. The mechanisms of the acid-catalyzed
      hydrolysis of 5b and 7b involve rate-limiting formation of benzylic carbocations
      (6b and 8b), which have sufficient lifetimes to be trapped by azide ion. Each
      carbocation is stabilized by the 6-methoxy group and held in single conformation
      by the adjacent trans-fused cyclohexane ring. The stereochemistry of the attack
      of water on each carbocation is independent of whether the precursor is an
      epoxide, a cis chlorohydrin, or a trans chlorohydrin, and the major diol
      hydrolysis product from each compound results from the axial attack of a solvent
      molecule on the carbocation intermediate. The hydrolysis of the trans
      chlorohydrin formed from the reaction of 5b with HCl exhibits a common ion rate
      depression. The major product from the pH-independent reaction of 5b is a trans
      diol, and the major product from the pH-independent reaction of 7b is an isomeric
      ketone. The rate of the pH-independent reaction of 7b is >10(4) times faster than
      that of 5b.

PMID- 16958519
TI  - An efficient and general route to gem-difluoromethylenated alpha,beta-unsaturated
      delta-lactones: high enantioselective synthesis of gem-difluoromethylenated
      goniothalamins.
AB  - An efficient and general strategy to gem-difluoromethylenated alpha,beta
      unsaturated delta-lactones in high yields from various aldehydes (including
      aliphatic, aromatic, alpha,beta-unsaturated, and sterically hindered aldehydes)
      has been developed. This methodology was successfully applied for the preparation
      of two enantiomers of gem-difluoromethylenated goniothalamins (S)-1 and (R)-1.
      gem-Difluoropropargylation of cinnamaldehyde followed by the resolution of
      resulting homopropargylic alcohols mediated by lipase from Pseudomonas (AK) gave
      alcohols (R)-6 and (S)-6. Selective hydrogenation of the triple bond of (S)-6 and
      (R)-6 to double bond with Lindlar catalyst in the presence of quinoline afforded
      the expected product (S)-8 and (R)-8, respectively. Deprotection of (S)-8 and (R)
      8 followed by oxidation of the resulting 1,5-diols with catalytic 2,2,6,6
      tetramethyl-1-piperidinyloxy (TEMPO) and excess bis-acetoxyiodobenzene (BAIB)
      provided the target molecules gem-difluoromethylenated goniothalamins (S)-1 and
      (R)-1 in high yields, respectively.

PMID- 16958520
TI  - Reactivity of molecular oxygen with ethoxycarbonyl derivatives of
      tetrathiatriarylmethyl radicals.
AB  - Tetrathiatriarylmethyl (TAM) radicals are commonly used as oximetry probes for
      electron paramagnetic resonance imaging applications. In this study, the
      electronic properties and the thermodynamic preferences for O2 addition to
      various TAM-type triarylmethyl (trityl) radicals were theoretically investigated.
      The radicals' stability in the presence of O2 and biological milieu was also
      experimentally assessed using EPR spectroscopy. Results show that H substitution
      on the aromatic ring affects the trityl radical's stability (tricarboxylate salt
      1-CO2Na > triester 1-CO2Et > diester 2-CO2Et > monoester 3-CO2Et) and may lead to
      substitution reactions in cellular systems. We propose that this degradation
      process involves an arylperoxyl radical that can further decompose to alcohol or
      quinone products. This study demonstrates how computational chemistry can be used
      as a tool to rationalize radical stability in the redox environment of biological
      systems and aid in the future design of more biostable trityl radicals.

PMID- 16958521
TI  - Directed molecular recognition: design and synthesis of neutral receptors for
      biotin to bind both its functional groups.
AB  - The neutral receptors 1 and 2 are designed and synthesized for the recognition of
      biotin, a biologically significant molecule, in chloroform to bind completely
      both of its functional groups simultaneously, i.e., cyclic urea and the carboxyl
      groups. The truncated receptor 3 binds only the cyclic urea moiety.

PMID- 16958522
TI  - Thiyl radical mediated racemization of nonactivated aliphatic amines.
AB  - The racemization of nonactivated aliphatic amines has been mediated with
      alkanethiols and with methyl thioglycolate in the presence of AIBN. The process
      involves reversible H-abstraction at the chiral center, in a position alpha
      relative to nitrogen, by thiyl radical. The knowledge of the reaction enthalpy is
      critical to select the appropriate thiol. In the absence of experimental values,
      theoretical calculations of the alpha-C-H BDEs and the S-H BDE provide a useful
      guide.

PMID- 16958523
TI  - On the mechanism of the selenolactonization reaction with selenenyl halides.
AB  - The mechanism of selenocyclization reactions of beta,gamma-unsaturated acids and
      their derivatives has been studied. The reactions of (E)-4-phenyl-3-butenoic acid
      10 and its silyl and alkyl esters with benzeneselenenyl chloride (PhSeCl) and
      bromide (PhSeBr) have been examined by VT-NMR and in situ IR spectroscopic
      methods. Whereas the reactions of the acid 10 in the presence of a base were
      irreproducible and complicated, reactions of the silyl esters were clean and
      spontaneously and quantitatively afforded a chloroselenylation adduct at -70
      degrees C as a single (Markovnikov) isomer. This adduct underwent three processes
      as the temperature was raised: (1) reversal to the starting materials, (2)
      isomerization to the anti-Markovnikov product, and (3) cyclization to the
      selenolactone 12. All of these processes are believed to proceed via a
      seleniranium ion the intermediacy of which was established by independent
      synthesis and spectroscopic identification. The reversible formation of chloro
      selenide adducts was unambiguously established by crossover experiments. The
      reaction of 10 with PhSeBr was found to be rapid but thermodynamically
      unfavorable at room temperature.

PMID- 16958524
TI  - Design and concise synthesis of fully protected analogues of l-gamma
      carboxyglutamic acid.
AB  - The design and synthesis of four nonnaturally occurring amino acid analogues of l
      gamma-carboxyglutamic acid (Gla), appropriately protected for Fmoc-based solid
      phase peptide synthesis (SPPS), is described. These amino acids are Bu-Mal 2,
      BCAH 3, Pen-Mal 4, and Cm-Gla 5. These Gla analogues have been designed to
      replace the glutamic acid of position 1 in the cyclic decapeptide G1TE, which is
      a potent inhibitor of tyrosine kinase, to further enhance binding to the Grb2-SH2
      domain of signal transduction receptors. In the new amino acids, the propionic
      acid side chain of Glu has been replaced by a malonyl or a carboxymethylmalonyl
      moiety located at different distances from the alpha-carbon to optimize
      interactions in the phosphotyrosine-binding cavity of the Grb2-SH2 domain.
      Additionally, a direct and efficient synthetic route for the preparation of Fmoc
      protected l-gamma-carboxyglutamic acid, which is amenable to large-scale
      production, has been developed to provide this important and unique amino acid(1)
      in 55% overall yield.

PMID- 16958525
TI  - A theoretical study of rhodium(I) catalyzed carbonylative ring expansion of
      aziridines to beta-lactams: crucial activation of the breaking C-N bond by
      hyperconjugation.
AB  - The regioselectivity and enantiospecificity of the [Rh(CO)2Cl]2-catalyzed
      carbonylative ring expansions of N-tert-butyl-2-phenylaziridine to yield 2
      azetidinone and the lack of reactivity of N-tert-butyl-2-methylaziridine along
      this process were investigated at the B3LYP/6-31G(d) (LANL2DZ for Rh) theory
      level taking into account solvent effects. According to our results, the
      regioselectivity in the ring expansion of N-tert-butyl-2-phenylaziridine and the
      unreactivity of N-tert-butyl-2-methylaziridine experimentally observed are
      determined by the different degree of activation of the breaking C-N bond in the
      initial aziridine-Rh(CO)2Cl complex due to its hyperconjugation interaction with
      the substituent on the carbon atom. When a phenyl substituent is present its
      hyperconjugation interaction with the C(alpha)-N bond facilitates the insertion
      of the metal atom into this bond. On the other hand, when the substituent is a
      methyl group, a larger stability of the initial complex along with a lower
      stabilization through hyperconjugation of the TS for insertion of the Rh atom
      into the C(alpha)-N bond make the ring expansion of N-tert-butyl-2
      methylaziridine unviable. The enantiospecificity experimentally observed is also
      reproduced by our calculations given that the stereogenic center is never
      perturbed to change its configuration.

PMID- 16958526
TI  - New modular and efficient approach to 6-substituted pyridin-2-yl C-nucleosides.
AB  - A novel modular, efficient, and practical methodology of preparation of 6
      substituted pyridin-2-yl C-nucleosides was developed. An addition of 2-lithio-6
      bromopyridine 2b to TBDMS-protected 2-deoxyribonolactone 5 gave aduct 7 as an
      equilibrium mixture of anomeric hemiketals 1-(6-bromopyridin-2-yl)-1
      hydroxynucleosides 7a,b and its open form 7c. Reduction of the adduct 7 with
      Et3SiH and BF3 x Et2O afforded the desired 6-bromonucleoside 8a as pure beta
      anomer in a total yield of 32% over two steps from 5. Intermediate 8a was then
      subjected to a series of palladium catalyzed cross-coupling reactions and
      aminations to give a series of protected 1beta-(6-alkyl-, 6-aryl-, and 6
      aminopyridin-2-yl)-2-deoxyribonucleosides 9. Catalytic hydrogenation of 8a gave
      an unsubstituted pyridine C-nucleoside, and diazotative oxodeamination of 6
      aminopyridine nucleoside 9f by isopentyl nitrite in acetic acid gave 6
      oxopyridine nucleoside 10i. Deprotection of silylated nucleosides 9 by Et3N.3HF
      gave a series of free C-nucleosides 10.

PMID- 16958527
TI  - Diosphenol-based approach to the a-ring functionalization of advanced Taxol
      precursors.
AB  - Several different approaches to the A-ring functionalization of an advanced,
      highly functionalized diosphenol precursor to Taxol are described. The first
      phase of the undertaking consists of an assessment of those reagents conducive to
      reaction at the enolic oxygen (silylation, methylation, allylation, and
      acylation). Transformations involving an alternative attack at the enol carbon
      center (bromination, selenation) have also been defined. Sodium borohydride
      reduction operates from the beta-face of C-14 as long as the C-1 hydroxyl is not
      protected so as to offer steric exclusion. Complications associated with various
      aspects of these methodological undertakings are addressed. The most advanced
      oxygenation achievements were realized by way of a noteworthy sequence involving
      epoxidation of the O-methyl ether, methanolysis under mildly acidic conditions,
      and regioselective oxidation of diol 38 to give 39.

PMID- 16958528
TI  - Diastereoselective synthesis of novel iminosugar-containing UDP-Galf mimics:
      potential inhibitors of UDP-Gal mutase and UDP-Galf transferases.
AB  - Tetra-O-benzyl-D-glucofuranose was converted into uridine diphosphono-beta-Galf
      mimics based on an iminosugar skeleton linked to UMP by a 2-hydroxypropyl tether.
      The synthesis is based on the highly regio- and stereoselective cycloaddition of
      an original uridin-5'-yl allylphosphonate with a 1,4-dideoxy-1,4-iminogalactitol
      derived cyclic nitrone, followed by the reductive elaboration of the
      cycloaddition product. The resulting iminogalactose-UMP conjugates are novel
      sugar nucleotide mimics which could be useful as inhibitors of UDP-Gal mutase and
      UDP-Galf transferases.

PMID- 16958529
TI  - Synthesis and optical resolution of aminophosphines with axially chiral C(aryl)
      N(amine) bonds for use as ligands in asymmetric catalysis.
AB  - N-Aryl indoline-type aminophosphines 1a-c were obtained in good yields by a
      nucleophilic aromatic substitution (S(N)Ar) reaction followed by silane
      reduction. Aminophosphine 1d was also prepared from 2,3-difluorobenzaldehyde (4)
      via dimethylhydrazone. Optical resolution of C(aryl)-N(amine) bond atropisomers
      was achieved using (S)-(+)-di-mu-chlorobis[2-[(dimethylamino)ethyl]phenyl
      C(2),N]dipalladium(II) ((S)-10). The determination of absolute configuration and
      the investigation of the rotation barrier for C(aryl)-N(amine) bond axial
      stability of an aminophosphine 1 are described. Finally, the ability of the
      chiral phosphine ligand 1 is demonstrated in a catalytic asymmetric reaction,
      such as a palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2
      propenyl acetate with dimethyl malonate (up to 95% ee).

PMID- 16958530
TI  - Total synthesis of the 7,3'-linked naphthylisoquinoline alkaloid
      ancistrocladidine.
AB  - The first total synthesis of ancistrocladidine, a rare 7,3'-linked
      naphthylisoquinoline alkaloid, has been completed, with the key feature of the
      synthesis being the formation of the extremely hindered biaryl linkage by ortho
      arylation of a naphthol with an aryllead triacetate. Initial efforts were focused
      on the generation of a heteroaryl lead species, which would have allowed a
      convergent synthesis to be developed. However, it was not possible to generate
      such a lead species. A simpler aryl lead triacetate was prepared and reacted. The
      resulting biaryl aldehyde was elaborated in 10 steps to form a 1:1 mixture of
      ancistrocladidine and its atropisomer. Recrystallization of the mixture afforded
      ancistrocladidine, which was identical in all respects to the reported data.

PMID- 16958531
TI  - Stereoselective syntheses of enantiomerically pure 2,5-disubstituted
      dihydropyrans based on olefin metathesis.
AB  - A short synthesis of 2,5-disubstituted dihydropyrans starting from d-mannitol as
      a chiral building block is described. Our synthetic approach combines ruthenium
      catalyzed ring closing olefin metathesis and palladium-catalyzed nucleophilic
      substitution.

PMID- 16958532
TI  - Synthetic approach toward the total synthesis of kempane diterpenes via
      transannular Diels-Alder strategy.
AB  - Total syntheses of two new (+/-)-kempane derivatives 30 and 47 were achieved with
      transannular Diels-Alder reaction (TADA) serving as the key step for the
      stereoselective formation of tricyclic [6.6.5] system 3. This synthetic approach
      also reveals that the geometry of the C3 group of such a tricyclic system plays
      an important role for the formation of the seven-membered kempane skeleton.

PMID- 16958533
TI  - Stereoselective preparation of a cyclopentane-based NK1 receptor antagonist
      bearing an unsymmetrically substituted sec-sec ether.
AB  - A highly efficient synthesis of the potent and selective NK-1 receptor antagonist
      1 is described. The key transformation involved the etherification reaction
      between cyclopentanol 12 and chiral imidate 30 which was catalyzed by HBF4 to
      initially give ether 14 as a 17:1 mixture of diastereomers and in 75% combined
      yield. The diastereoselectivity was upgraded to 109:1 by crystallization of the
      triethylamine solvate 44 which was isolated in 54% yield from 12. Mechanistic
      studies confirmed that the etherification reaction proceeds through an
      unprecedented S(N)2 reaction pathway under typical S(N)1 reaction conditions.

PMID- 16958534
TI  - Synthesis of the tetracyclic framework of the erythrina alkaloids using a [4 + 2]
      cycloaddition/Rh(I)-catalyzed cascade of 2-imidofurans.
AB  - Several 2-imido substituted furans were found to undergo a rapid intramolecular
      [4 + 2]-cycloaddition to deliver oxabicyclo adducts in good to excellent yields.
      By using a Rh(I)-catalyzed ring opening of the resulting oxabicyclic adduct, it
      was possible to prepare several highly functionalized tetrahydro-1H-indol-2(3H)
      one derivatives which were then used to prepare several erythrina alkaloids. By
      taking advantage of the Rh(I)-catalyzed reaction, it was possible to convert tert
      butyl 3-oxo-5-carbomethoxy-10-oxa-2-azatricyclo[5.2.1.0(1,5)]dec-8-ene-2
      carboxylate into the ring opened boronate by reaction with phenylboronic acid.
      Treatment of the boronate with pinacol/acetic acid afforded the corresponding
      diol which was used in a successful synthesis of racemic 3
      demethoxyerythratidinone. During the course of these studies, several novel
      rearrangement reactions were encountered while attempting to induce an acid
      initiated Pictet Spengler cyclization of a key lactam intermediate. The
      IMDAF/Rh(I)-catalyzed ring opening cascade sequence was also applied to the total
      synthesis of (+/-)-erysotramidine as well as the lycorine type alkaloid (+/-)-epi
      zephyranthine.

PMID- 16958535
TI  - Iterative synthesis of deoxypropionate units: the inductor effect in acyclic
      conformation design.
AB  - Conjugate addition of lithium dimethylcuprate to acyclic alpha,beta-unsaturated
      esters of varying lengths bearing terminal alkyl or phenyl groups leads to a
      preponderance of syn 1,3-adducts when one methyl is already present. Conversion
      to enoates, and iteration of cuprate additions also favors syn adducts to give
      contiguous deoxypropionate units in a growing chain. The effect of end-group
      variation (Me, i-Pr, phenyl, tert-butyl) in conjunction with the nature of the
      ester group (Me, tert-butyl, etc.) on the diastereoselectivity of syn and anti
      products was studied. The results are rationalized in terms of inductor effects
      related to the minimization of the 1,5-pentane interactions in energetically
      favored folded conformations and corroborated by homodecoupling NMR studies.

PMID- 16958536
TI  - Trimesitylmethylphosphonium cation. Supramolecular stereocontrol and simple
      enantiomerization mechanism determination.
AB  - Stereocontrol over the propeller isomerism of trimesitylmethylphosphonium cation
      was achieved through an ion pairing with chiral hexacoordinated phosphate anions;
      the asymmetric ion pairing allowed also a most simple experimental proof of the
      nature of the enantiomerization pathway in solution (two-ring flip).

PMID- 16958537
TI  - Two-photon photochemical generation of reactive enediyne.
AB  - p-Quinoid cyclopropenone-containing enediyne precursor (1) has been synthesized
      by monocyclopropanation of one of the triple bonds in p-dimethoxy-substituted 3,4
      benzocyclodeca-1,5-diyne followed by oxidative demethylation. Cyclopropenone 1 is
      stable up to 90 degrees C but readily produces reactive enediyne 2 upon single
      photon (Phi(300)(nm) = 0.46) or two-photon (sigma(800 nm) = 0.5 GM) photolysis.
      The photoproduct 2 undergoes Bergman cyclization at 40 degrees C with the
      lifetime of 88 h.

PMID- 16958538
TI  - Novel diethynylcarbazole macrocycles: synthesis and optoelectronic properties.
AB  - Diethynylcarbazole macrocycles 1b and 2b have been synthesized by oxidative
      coupling of appropriate precursors. In particular, macrocycle 2b was prepared by
      bimolecular Pd-catalyzed oxidative coupling in 35% isolated yield. The
      spectroscopic properties of these macrocycles and their precursors were measured
      in detail. The films of these macrocycles by the dipping method and the Langmuir
      Blodgett technique were fabricated to study their photoinduced charge-transfer
      properties. A rapid and steady cathodic photocurrent of these films was produced
      in a three-electrode cell when irradiated with white light. A possible mechanism
      of the photoinduced electron-transfer pathway was suggested.

PMID- 16958539
TI  - Oxidations of secondary alcohols to ketones using easily recyclable
      bis(trifluoroacetate) adducts of fluorous alkyl iodides, CF3(CF2)(n-1)I(OCOCF3)2.
AB  - Reactions of commercial fluorous alkyl iodides RfnI (1-Rfn; Rfn = CF3(CF2)(n-1);
      n = 7, 8, 10, 12) with 80% H2O2 and trifluoroacetic anhydride give RfnI(OCOCF3)2
      (2-Rfn; 97-89%). These efficiently oxidize aliphatic and benzylic secondary
      alcohols to the corresponding ketones (92-57%) in the presence of aqueous KBr and
      absence of organic or fluorous solvents. Bromide ion activates the reagents
      and/or generates a relay oxidant such as a functional equivalent of Br+.
      Oxidations are much more rapid (<30 min, 2-R(f8); <70 min, 2-R(f10)) than with
      other iodine(III) compounds under similar conditions. The coproducts 1-Rfn can be
      recovered by adding 3-5 volumes of methanol to the reaction mixtures.
      Fluorous/methanolic liquid/liquid (1-R(f8)) or solid/liquid (1-R(f10)) biphase
      systems result. The recovered 1-Rfn can be reoxidized to 2-Rfn and reused. Three
      cycles are conducted with 1-phenyl-1-propanol and 2-R(f10). The propiophenone
      yields range from 92% to 83% per cycle, and after the final cycle 59-57% of the
      original charge of the fluorous iodide species is recovered.

PMID- 16958540
TI  - Self-assembled hemicapsules with inherent functionalities: modeling of a
      supramolecular electrostatic self-assembly.
AB  - An approach to functional self-assembled hemicapsules is described consisting of
      the use of multivalent (valency > or = 4) and divalent components, the functional
      groups of which have a relatively weak binding affinity. Electrostatic self
      assembly of tetrakis(pyridiniummethyl)cavitand hemispheres (H) and doubly charged
      anions (A) in polar media gives rise to an equilibrium mixture that consists, as
      detected with ESI-MS, of hemicapsule H2A3, capsule H2A4, and other ion-pair
      associates. Fitting 1H NMR data with a model that includes (hemi)capsules and ion
      pair associates gave an effective molarity (EM) for the intramolecular assembly
      of the host (H) with sulfate (A) of 0.19 +/- 0.02 M and binding constants of the
      functional [2 + 3] hemicapsules H2A3 and the [2 + 4] capsules H(2)A(4) in
      methanol of 3.25 x 10(12) M(-4) and 3.45 x 10(15) M(-5), respectively. A
      substantial amount of the functional [2 + 3] hemicapsules H2A3 with respect to [2
      + 4] capsules H2A4 is present in solution, with ratios of H2A3 to H2A4 of 5.67
      0.43 in the studied concentration range (0.1-25 mM of [H]tot). The [2 + 3]
      hemicapsules H2A3 built with sulfate linkers incorporate guests between the
      closely positioned pyridinium planes.

PMID- 16958541
TI  - Preparation of allyl sulfoxides by palladium-catalyzed allylic alkylation of
      sulfenate anions.
AB  - Palladium-catalyzed allylic alkylation of sulfenate anions, generated from beta
      sulfinylesters by retro-Michael reaction, can take place under biphasic
      conditions. This new reaction provides a simple, mild, and efficient route to
      allyl sulfoxides in good yields.

PMID- 16958542
TI  - Highly efficient C-C bond-forming reactions in aqueous media catalyzed by
      monomeric vanadate species in an apatite framework.
AB  - A calcium vanadate apatite (VAp), in which PO4(3-) of hydroxyapatite (HAP),
      Ca10(PO4)6(OH)2, is completely substituted by VO4(3-) in the apatite framework,
      was synthesized. Physicochemical analysis of the VAp reveals the presence of
      isolated VO4 tetrahedron units with a pentavalent oxidation state. The VAp acts
      as a high-performance heterogeneous base catalyst for various carbon-carbon bond
      forming reactions such as Michael and aldol reactions in aqueous media and the H
      D exchange reactions using deuterium oxide. For example, a 200-mmol-scale Michael
      reaction under triphasic conditions proceeded rapidly, with an extremely high
      turnover number of up to 260 400 and an excellent turnover frequency of 48 s(-1).
      No vanadium leaching was detected during the above reactions, and the catalyst
      was readily recycled with no loss of activity.

PMID- 16958543
TI  - Conversion of propargyl alcohols to chloroallenes and arylalkynes using the
      TiCl4/R3N reagent system.
AB  - Whereas the reaction of certain propargyl alcohols with TiCl4 in the presence of
      tertiary alkylamines gives the corresponding chloroallenes in 37-58% yields,
      reaction with the tertiary arylamines gives the corresponding arylalkynes in 68
      77% yields.

PMID- 16958544
TI  - Pd-mBDPP-catalyzed regioselective internal arylation of electron-rich olefins by
      aryl halides.
AB  - meso-2,4-Bis(diphenylphosphino)pentane (mBDPP) has proved to be an effective
      regiocontrolling ligand for palladium-catalyzed internal arylation by aryl
      bromides of electron-rich olefins in a common solvent DMSO with no need for any
      halide scavengers. The arylation of the benchmark electron-rich olefin butyl
      vinyl ether took place smoothly to afford exclusively alpha-arylated product with
      high isolated yields. The better performance of mBDPP, compared with that of the
      commonly used DPPP [1,3-bis(diphenylphosphino)propane], highlights the important
      but subtle effect of ligand on the regioselectivity of the Heck arylation
      reactions.

PMID- 16958545
TI  - Ring opening and expansion of aziridines in a silica-water reaction medium.
AB  - Ring-opening reactions of N-tosylaziridines with water-soluble nucleophiles
      proceeded in a silica-water reaction medium. The system is applicable to a ring
      expansion of an aziridine with potassium thiocyanate, leading to a thiazolidine
      derivative.

PMID- 16958546
TI  - A sulfitylation-oxidation protocol for the preparation of sulfates.
AB  - A novel, high-yielding method for sulfation of alcohols has been developed,
      proceeding via sulfite- and sulfate diester intermediates. Sulfite diesters serve
      as versatile sulfate monoester precursors, allowing for transformations that are
      difficult or impossible with the latter compounds.

PMID- 16958547
TI  - Template synthesis of [2]rotaxanes with large ring components and
      tris(biphenyl)methyl group as the blocking group. The relationship between the
      ring size and the stability of the rotaxanes.
AB  - We synthesized a series of macrocyclic phenanthrolines 3a-e and a
      tris(biphenyl)methyl derivative 4. [2]Rotaxanes with large ring components
      (10a,b) were synthesized by the template method, and the stability of the
      rotaxanes was examined. The study revealed that the tris(biphenyl)methyl group is
      an effective blocking group for the rotaxanes with up to a 33-membered ring. Even
      a rotaxane with a 37-membered macrocyclic phenanthroline (10b) could be isolated.
      The dissociation of 10b occurred at 60 degrees C.

PMID- 16958548
TI  - Highly chemoselective formation of aldehyde enamines under very mild reaction
      conditions.
AB  - Although ketone enamines are widely used in organic synthesis, aldehyde enamines
      are rarely employed due to the limitations of their preparation using known
      methods (need for acid or base, excess of amine, and/or elevated temperature). We
      have successfully developed rapid and particularly mild condensation conditions
      (1 h, 0 degrees C, 1.2 equiv of amine) leading to di- and trisubstituted enamines
      with excellent conversion (84-100%). Remarkably high chemoselectivity was
      observed with complete discrimination between aldehyde and ketone, among other
      functional groups positively tested.

PMID- 16958549
TI  - Diatomite-supported Pd nanoparticles: an efficient catalyst for Heck and Suzuki
      reactions.
AB  - The Pd nanoparticles immobilized on natural diatomite were achieved by a simple
      procedure. The catalysts are highly active for Heck and Suzuki reactions and can
      be recovered and reused many times. The catalytic process was also investigated.

PMID- 16958550
TI  - Reusable copper-catalyzed cross-coupling reactions of aryl halides with
      organotins in inexpensive ionic liquids.
AB  - A combination of Cu2O nanoparticles with P(o-tol)3 shows highly catalytic
      activity for the Stille cross-coupling reaction. A series of copper catalysts and
      ligands were evaluated, and Cu2O nanoparticles combined with P(o-tol)3 provided
      the best results. In the presence of Cu2O nanoparticles and P(o-tol)3, a variety
      of aryl halides including aryl chlorides underwent the Stille reaction with
      organotins smoothly in moderate to excellent yields using inexpensive TBAB (n
      Bu4NBr) as the medium. It is noteworthy that the Cu2O/P(o-tol)3/TBAB system can
      be recovered and reused at least three times without any loss of catalytic
      activity among the reactions of aryl iodides and activated aryl bromides.

PMID- 16958551
TI  - Linchpin synthons: metalation of aryl bromides bearing a potassium
      trifluoroborate moiety.
AB  - Aryl bromides bearing a potassium trifluoroborate moiety were subjected to
      lithium-halogen exchange at low temperature using a variety of alkyllithium
      reagents. A number of different electrophiles were evaluated in their reactions
      with the aryllithiums produced therein. Under carefully optimized conditions,
      potassium bromophenyl trifluoroborates afforded good to excellent yields of the
      corresponding alcohols (64-94% isolated yield) when aldehydes or ketones were
      used as the electophilic partner. Esters were unfortunately found to be
      unreactive.

PMID- 16958552
TI  - Stereoselective synthesis of highly functionalized nitrocyclopropanes via
      organocatalyic conjugate addition to nitroalkenes.
AB  - A convenient and novel one-pot organocatalytic methodology for the
      stereoselective synthesis of highly functionalized nitrocyclopropanes is
      reported. The addition of dimethyl chloromalonate to a variety of nitroolefins
      catalyzed by tertiary amines leads to a Michael adduct which cyclizes to form the
      cyclopropane in the presence of DBU under carefully controlled reaction
      conditions with outstanding diastereoselectivity.

PMID- 16958554
TI  - Veratrum poisoning.
AB  - Several species of the Veratrum genus are associated with toxicity in humans and
      animals. The principal toxins are steroid alkaloids; some have a modified steroid
      template, whereas others differ in their esterified acid moieties. These
      alkaloids act by increasing the permeability of the sodium channels of nerve
      cells, causing them to fire continuously. Increased stimulation, associated with
      the vagal nerve results in a reflex that causes the triad of responses known as
      the Bezold-Jarisch reflex: hypotension, bradycardia and apnoea. Clinically,
      various Veratrum extracts were marketed for clinical use as antihypertensive
      drugs, but because of their narrow therapeutic index were withdrawn from the
      market. Following the ingestion of Veratrum alkaloids, expected signs and
      symptoms include vomiting and abdominal pain, followed by cardiovascular effects
      such as bradycardia, hypotension and cardiac conduction abnormalities and death.
      Similar symptoms arise in other mammalian species ingesting these alkaloids;
      teratogenic effects may occur to the fetuses of animals that have grazed on
      Veratrum californicum. Treatment consists of supportive care, with an emphasis on
      haemodynamic stability with fluid replacement, atropine and vasopressors. The
      onset of symptoms occurs between 30 minutes and 4 hours, and the duration of the
      illness can range from 1 to 10 days; however, with prompt supportive care,
      patients typically make a full recovery within 24 hours.

PMID- 16958556
TI  - The value of morphological neuroimaging after acute exposure to toxic substances.
AB  - Many toxic agents induce brain dysfunction and/or lesions. Modern neuroimaging
      techniques, such as CT and more recently magnetic resonance imaging (MRI), are
      able to demonstrate toxic brain lesions at both early and delayed phases of
      disease progression. In the early phase, neuroimaging enables the detection of
      acutely injured brain areas responsible for sudden onset of neurological
      dysfunction, but the severity and the extension of brain lesions on neuroimages
      do not necessarily parallel the severity of the clinical status. In the chronic
      phase, when neurological dysfunction has become permanent, neuroimaging allows
      precise identification of neuroanatomical sequelae that do not necessarily match
      the severity of the chronic neurological impairment. Papers in the medical
      imaging literature have dealt mainly with the brain changes induced by 'chronic
      exposure' to toxic substances such as solvents or heavy metals. This article
      selectively reviews the main radiological changes observed on CT/magnetic
      resonance (MR) neuroimages after 'acute exposure' to industrial products
      (methanol [methyl alcohol], ethylene glycol), environmental agents (cyanide,
      carbon monoxide), pharmaceuticals (insulin, valproic acid) and illicit substances
      (heroin, cocaine). Different kinds of lesions, which lack specificity for toxic
      injury, can be observed on radiological images, but deep grey matter lesions with
      symmetrical distribution throughout basal ganglia are most often seen. However,
      such findings have also been reported after anoxic-ischaemic insults or during
      severe metabolic disturbances. Lesions in the white matter may also be present in
      the case of acute exposure to toxic agents. The true prognostic value of toxic
      induced brain changes in the acute phase in CT or MR studies is unclear, although
      serial MRI may add new information as may quantitative or molecular imaging
      techniques such as the MR diffusion-weighted imaging or MR spectroscopy.

PMID- 16958555
TI  - Does high-dose buprenorphine cause respiratory depression?: possible mechanisms
      and therapeutic consequences.
AB  - Buprenorphine is an opioid agonist-antagonist with a 'ceiling effect' for
      respiratory depression. Compared with methadone, its unique pharmacology offers
      practical advantages and enhanced safety when prescribed as recommended and
      supervised by a physician. Buprenorphine has been approved in several countries
      as an efficient and safe maintenance therapy for heroin addiction. Its use
      resulted in a salutary effect with a reduction in heroin overdose-related deaths
      in countries that implemented office-based buprenorphine maintenance. In France,
      however, where high-dose buprenorphine has been marketed since 1996, several
      cases of asphyxic deaths were reported among addicts treated with buprenorphine.
      Death resulted from buprenorphine intravenous misuse or concomitant sedative drug
      ingestion, such as benzodiazepines. In these situations of abuse, misuse, or in
      association with elevated doses of psychotropic drugs, buprenorphine may cause
      severe respiratory depression. Unlike other opiates, the respiratory effects from
      buprenorphine are not responsive to naloxone. However, the exact mechanism of
      buprenorphine-induced effects on ventilation is still unknown. The role of
      norbuprenorphine, the main N-dealkylated buprenorphine metabolite with potent
      respiratory depressor activity, also remains unclear. Experimental studies
      investigating the respiratory effects of combinations of high doses of
      buprenorphine and benzodiazepines suggested that this drug-drug interaction may
      result from a pharmacodynamic interaction. A pharmacokinetic interaction between
      buprenorphine and flunitrazepam is also considered. As there are many questions
      regarding the possible dangers of death or respiratory depression associated with
      buprenorphine use, we aimed to present a comprehensive critical review of the
      published clinical and experimental studies on buprenorphine respiratory effects.

PMID- 16958557
TI  - The early toxicology of physostigmine: a tale of beans, great men and egos.
AB  - Mid-19th century European visitors to Old Calabar, an eastern province of
      Nigeria, could not avoid becoming aware of native belief in the power of the
      seeds of a local plant to determine whether individuals were innocent or guilty
      of some serious misdemeanour. The seeds were those of a previously unknown legume
      and soon referred to as the ordeal bean of Old Calabar. Their administration was
      known locally as 'chop nut'. Missionaries who arrived in Calabar in 1846
      estimated that chop nut caused some 120 deaths annually and documented the course
      of poisoning. The latter information and samples of the beans rapidly found their
      way to Scotland, the home of the missionaries' parent church, explaining why the
      early toxicology of physostigmine, quantitatively the most important of three
      active alkaloids in the beans, has such strong Scottish, predominantly Edinburgh,
      associations. However, it was 1855 before the first of many medical scientists,
      Robert Christison, a toxicologist of repute, investigated the effects of the
      beans to the extent of eating part of one himself and documenting the moderate,
      if not severe, consequences. A further 6 years were to pass before Balfour's
      comprehensive botanical description of the bean plant appeared. It was he who
      named it Physostigma venenosum. It was not so long until the next event, one that
      sparked more intensive and international interest in the beans. In 1863 a young
      Edinburgh ophthalmologist, Argyll Robertson, published a paper announcing the
      arrival of the first agent that constricted the pupil of the eye. The drug was an
      extract of Calabar beans and Argyll Robertson openly admitted that he had been
      alerted to its unusual property by his physician friend, Thomas Fraser. A minor
      flood of contributions on the ophthalmic uses of bean extracts followed in the
      medical press in the next few months; those on their systemic toxicity were
      fewer. Fraser's MD thesis, submitted to the University of Edinburgh in 1862 and
      clearly pre-dating Argyll Robertson's involvement with the beans, became
      generally available a few weeks after the appearance of Argyll Robertson's paper
      and was the first to address in detail the features of systemic administration of
      extracts of the beans. A major problem facing all early researchers of the beans
      was that of deciding how best to extract their active principle, a task made all
      the more difficult because bioassays were the only means of determining if the
      toxin was being tracked. The stability of extracts was an inevitable issue and
      the active principle finally became known as physostigma or physostigmine, after
      the botanical name of the parent plant. The features of physostigmine toxicity
      were soon exhaustively documented, both in animals and humans. How they were
      mediated was another matter altogether. Fraser maintained that muscular
      paralysis, the cardinal feature, was the result of depression of the spinal cord
      and was generally, but far from unanimously, supported. Of those who had
      reservations, Harley was the most prominent. He concluded that paralysis was
      secondary to effects on the motor nerve endings and, in so doing, came nearest to
      present-day knowledge at a time when acetylcholine, cholinesterases and
      cholinesterase inhibitors were not even imagined. Differences of opinion on the
      mode of action of the beans were to be expected and it is hardly surprising that
      they were not resolved. No standard formulation of physostigmine was available so
      the potency of those used would have varied from one investigator to another, the
      range of animals experimented upon was large while the number used by any
      researcher was commonly in single figures, more readily available cold-blooded
      creatures seemed less sensitive to physostigmine toxicity than warm-blooded ones
      and only Fraser determinedly pursued an answer; in general, the others made one
      foray into bean research then turned their attentions elsewhere. The same
      problems would beset other aspects of bean research. While Fraser did not get as
      close to the mode of action of physostigmine as Harley, he reigns supreme when it
      comes to antagonism between physostigmine and atropine. By this time, the 1870s
      had dawned and although the concept of antagonism between therapeutic agents was
      not new, it had little, if any, reliable scientific foundation. This was about to
      change; antagonism was becoming exciting and rational. Fraser's firm belief that
      physostigmine and atropine were mutually antagonistic at a physiological level
      was contrary to the conventional wisdom of his contemporaries. This alone would
      earn him a place in history but his contribution goes much, much further. Unlike
      any other at the time, he investigated it with scientific rigour, experimenting
      on only one species, ensuring as best he could the animals were the same weight,
      adjusting the doses of drugs he gave them for bodyweight, determining the minimum
      lethal dose of each drug before assessing their antagonistic effects, adopting a
      single, incontrovertible endpoint for efficacy and carrying out sufficient
      numbers of experiments to appear convincing in a later era where the statistical
      power of studies is all-important. To crown it all, he presented his results
      graphically. Fraser never claimed to have discovered the antagonism between
      physostigmine and atropine. Bartholow in 1873 did, based on work done in 1869.
      But his data hardly justify it. If anyone can reasonably claim this particular
      scientific crown it is an ophthalmologist, Niemetschek, working in Prague in
      1864. His colleague in the same discipline, Kleinwachter, was faced with treating
      a young man with atropine intoxication. Knowing of the contrary actions of the
      two drugs on the pupil, Niemetschek suggested that Calabar bean extract might be
      useful. Kleinwachter had the courage to take the advice and his patient improved
      dramatically. Clearly, this evidence is nothing more than anecdotal, but the
      ophthalmologists were correct and, to the present day, physostigmine has had an
      intermittent role in the management of anticholinergic poisoning. The converse,
      giving atropine to treat poisoning with cholinesterase inhibitors, of which
      physostigmine was the first, has endured more consistently and remains standard
      practice today. It is salutary to realise that the doses and dosage frequency of
      atropine together with the endpoints that define they are adequate were
      formulated by Fraser and others a century and a half ago.

PMID- 16958558
TI  - Calculated ultraviolet exposure levels for a healthy vitamin D status.
AB  - The dangers of overexposure to sunlight have been well publicized, but less
      attention has been given to an acknowledged benefit of exposure to UV radiation;
      that being the cutaneous synthesis of vitamin D3. Here we define a standard
      vitamin D dose on the basis of recently recommended requirements for vitamin D
      that take account of its risk reduction role in a variety of diseases, and
      present a web-based tool that enables the reader to calculate associated exposure
      times for any time and place using either default values or user-selected
      conditions. Either it is not possible to synthesize vitamin D3 at high latitudes
      in winter, or the exposure time required to reach a standard dose is sometimes
      impractical. Where solar UV is sufficient, a risk-benefit analysis of sunburn vs.
      vitamin D3 synthesis shows that the best time for brief sun exposure is in the
      middle of the day. For low solar elevation angles common at high latitudes, a
      fine line exists between adequate UV exposure for vitamin D3 synthesis and a risk
      of sun burn.

PMID- 16958560
TI  - Chemokine antagonists as therapeutics: focus on HIV-1.
AB  - Human immunodeficiency virus type 1 (HIV-1) entry into target cells is a
      multistep process involving the interaction of viral envelope proteins with cell
      surface receptors. Binding to CD4 is followed by engagement of specific chemokine
      receptors (CCR5 or CXCR4), triggering molecular rearrangements in the envelope
      transmembrane subunit that result in membrane fusion. Chemokine receptor
      antagonists that block the interaction of the HIV-1 envelope with CCR5 or CXCR4
      potently inhibit HIV-1 in vitro. Pilot studies of orally bioavailable small
      molecule CCR5 inhibitors in HIV-1-infected subjects have provided proof of
      concept for this novel drug class; phase III safety and efficacy trials are under
      way.

PMID- 16958559
TI  - Distribution and translocation of photoreceptor Gbetagamma-phosducin system in
      medaka retina.
AB  - Unlike other vertebrates, teleosts have rod- and cone-specific phosducins (PD-R
      and PD-C) in the retina. To evaluate the teleost Gbetagamma-PD systems, we
      isolated cDNAs encoding medaka Gbeta1 and GbetaC, which selectively expressed
      rods and cones. Immunohistochemical studies showed that the strong reactivity of
      GbetaC but not PD-C was detected in cone outer segments. In rod outer segments
      (ROS), PD-R reactivity was stronger in light-adapted retina than in dark-adapted
      retina. Western blot analyses of fractions torn from the cryosections showed that
      the PD-R concentration was low in dark-adapted ROS. It is suggested that PD-R is
      translocated to ROS and effectively downregulates the phototransduction cascade
      in light-adapted rods.

PMID- 16958561
TI  - Idiosyncratic toxicity: a convergence of risk factors.
AB  - The therapeutic margin for any drug is based on both toxicity and efficacy.
      Generally, toxicity is dose-dependent and is driven either by the therapeutic
      target or by an untoward target. However, idiosyncratic toxicities are usually
      not observed until a drug has been on the market and has gained broad exposure.
      Except in the case of pharmacokinetic interactions, these toxicities are not
      driven solely by drug exposure but rather depend on several drug- and patient
      related risk factors. Drug-related risk factors include metabolism, bioactivation
      and covalent binding, and the inhibition of key cell functions. Patient-related
      risk factors include underlying disease, age, gender, comedications, nutritional
      status, activation of the innate immune system, physical activity, and genetic
      predispositions. Idiosyncratic toxicity can occur when a convergence of risk
      factors, including drug exposure, tips the risk-benefit balance away from benefit
      and toward risk.

PMID- 16958562
TI  - Regulations and procedures for new drug evaluation and approval in China.

PMID- 16958563
TI  - Elucidating the role of risperidone in the treatment of disruptive behavior
      disorders.

PMID- 16958564
TI  - Risperidone in the management of disruptive behavior disorders.
AB  - Disruptive behavior disorders (DBDs) represent a spectrum of disorders, including
      conduct disorder and oppositional-defiant disorder. The atypical antipsychotic
      risperidone may be useful for the management of patients with DBDs. Clinical data
      on risperidone have demonstrated efficacy and satisfactory tolerability in
      improving angry, aggressive, self-injurious, and disruptive symptoms and behavior
      in children with pervasive developmental disorders and mood disorders. This paper
      reviews the results of recent studies that have evaluated the efficacy and safety
      of risperidone in the treatment of pediatric patients with DBDs. Because concerns
      have been raised regarding the safety of atypical antipsychotic treatment in
      pediatric patients, this paper further evaluates safety risks by presenting newly
      completed analyses of movement disorders, prolactin concentrations, body weight,
      and cognitive function data from short- and long-term studies in this patient
      population. A comprehensive review of all of the findings suggests that
      risperidone is an effective and well-tolerated treatment option for children and
      adolescents with DBDs. As with all antipsychotics, practitioners should monitor
      young patients' growth, weight, sexual maturation, and metabolic parameters.

PMID- 16958565
TI  - An open-label randomized comparison of olanzapine versus risperidone in the
      treatment of childhood-onset schizophrenia.
AB  - BACKGROUND AND PURPOSE: Childhood-onset schizophrenia (COS) is a clinically
      severe form of schizophrenia, which causes severe impairment to cognitive,
      linguistic, and social development. There are few prospective and retrospective
      open clinical trials of risperidone and olanzapine in COS. In this open-label,
      randomized, prospective study, we compared the tolerability and effectiveness of
      risperidone versus olanzapine in the treatment of COS patients. METHODS: The
      study population consisted of 25 children with COS (mean age 11.09 +/- 1.55
      years). After an evaluation, patients received risperidone (0.25-4.5 mg/day, mean
      dose 1.62 +/- 1.02 mg/day) or olanzapine (2.5-20 mg/day, mean dose 8.18 +/- 4.41
      mg/day) for 12 weeks, with weekly evaluations. RESULTS: Both groups showed
      comparable significant (p < 0.001) within-group improvement from baseline to
      endpoint (LOCF) in Positive and Negative Symptoms Scale (PANSS) total and
      subscale scores. Of the olanzapine-treated children, 11 (91.7%) completed the 12
      weeks of the study, whereas in the risperidone-treated children only 9 (69.2%)
      did. No significant differences between risperidone-treated children and
      olanzapine-treated children were observed on Barnes Akathisia Rating Scale (BAS)
      and Simpson-Angus Scale (SAS) rating scales. Both treatment groups showed
      significant (p < 0.001) increase in weight from baseline to endpoint. CONCLUSION:
      Our open-label, small-scale comparative study suggests that both risperidone and
      olanzapine appear to be efficacious antipsychotic medications in COS, with a
      slight nonsignificant advantage of olanzapine in the dropout rate.

PMID- 16958566
TI  - Placebo-controlled study examining effects of selegiline in children with
      attention-deficit/hyperactivity disorder.
AB  - There is evidence suggesting a role for dopamine in attention
      deficit/hyperactivity disorder (ADHD). Pharmacological treatments that act on the
      dopamine system have been successful in reducing ADHD symptoms. However, unlike
      traditional stimulants (i.e., methylphenidate), selegiline is a monoamine oxidase
      inhibitor (MAOI) that has been shown to reduce ADHD symptoms without producing
      undesirable side effects. In this study using a randomized, double- blind,
      placebo-controlled, crossover design, cognitive tasks and behavioral rating
      scales were administered to measure the effectiveness of selegiline in treating
      different symptoms of ADHD in 11 children aged 6-13. Results indicate that
      selegiline may target specific symptoms of ADHD including: sustained attention,
      the learning of novel information, hyperactivity, and peer interactions. Because
      the drug was not associated with negative side effects and did not specifically
      reduce symptoms of impulsivity, selegiline may be a preferred treatment for
      individuals who present with the primarily inattentive subtype of ADHD.

PMID- 16958567
TI  - Methylphenidate blood levels and therapeutic response in children with attention
      deficit hyperactivity disorder: I. Effects of different dosing regimens.
AB  - BACKGROUND AND PURPOSE: Methylphenidate (MPH) is a drug of choice for treating
      attention-deficit/hyperactivity disorder (ADHD), although its use has been
      complicated by its short duration of action. The development of ideal long-acting
      preparations requires detailed understanding of the pharmacokinetic and
      pharmacodynamic consequences of complex dosing regimens. The purpose of this
      study was to ascertain if administration paradigms that produce stable or rising
      MPH levels alter the rate with which MPH is absorbed, and to determine how
      effectively long-acting administration paradigms compare with thrice daily
      administration of immediate-release MPH. METHOD: Forty-eight boys diagnosed with
      ADHD (mean age 10.6 +/- 1.1 year) participated in this double-blind, parallel
      group study to evaluate the pharmacokinetics and efficacy and of 1 mg/kg/day MPH
      administered in five different paradigms and placebo. Objective measures of
      activity and attention (McLean Motion Attention Test; M-MAT) and plasma measures
      of d- and l-MPH were obtained hourly during the course of a 12-hour laboratory
      session. RESULTS: The rate of absorption and elimination of d-MPH was dependent
      on the pattern of administration, particularly on the initial bolus
      concentration. This suggests that d-MPH may act on the gastrointestinal system to
      slow absorption of additional d-MPH. There were significant differences among
      regimens on time course and degree of therapeutic response. Pulsatile
      administration produced greater improvement than escalating levels.

PMID- 16958568
TI  - Parents report on stimulant-treated children in the Netherlands: initiation of
      treatment and follow-up care.
AB  - OBJECTIVES: The aim of this study was to describe current practices around
      initiation and follow-up care of stimulant treatment among stimulant-treated
      children in a nationwide survey among parents. METHODS: A total of 115 pharmacies
      detected current stimulant users <16 years old in their pharmacy information
      system and sent parents a questionnaire regarding their child's stimulant
      treatment. RESULTS: Parents returned 924 of 1,307 questionnaires (71%). The
      median age of the stimulant users was 10 years and 85% were boys. In all, 91%
      were diagnosed with attention-deficit/hyperactivity disorder (ADHD). In 77% of
      the cases, the child or parents received other therapies besides stimulants-21%
      received psychotropic co-medication, with melatonin (11%) and antipsychotics (7%)
      being mentioned most frequently. Stimulant use was primarily initiated by child
      psychiatrists (51%) and pediatricians (32%), but most children received repeat
      prescriptions from general practitioners (61%). Of these 924 children, 19% did
      not receive any follow-up care, and transfer of prescribing responsibility
      increased the risk of not receiving follow-up care. The 732 children (79%) who
      were monitored visited a physician approximately twice a year. During follow-up
      visits, pediatricians performed physical check ups significantly more often.
      CONCLUSION: Stimulant treatment in The Netherlands is initiated mainly by
      specialists such as child psychiatrists and pediatricians. In the current study,
      follow-up care for stimulant-treated children in The Netherlands appeared to be
      poor, suggesting an urgent need for improvement.

PMID- 16958569
TI  - An open-label, randomized, active-controlled equivalent trial of osmotic release
      oral system methylphenidate in children with attention-deficit/hyperactivity
      disorder in Taiwan.
AB  - This study examined the efficacy and safety of osmotic release oral system
      methylphenidate (OROS MPH) as compared with immediate-release MPH (IR MPH) in
      children with attention-deficit/hyperactivity disorder (ADHD) in Taiwan. Sixty
      four children with Diagnostic and Statistical Manual of Mental Disorders, 4th
      edition (DSM-IV) ADHD, ages 6-15 years, were randomized to OROS MPH once daily (n
      = 32) and IR MPH three times daily (n = 32) in an open, randomized, active
      controlled equivalent 28-day trial. The main outcome measures included the
      Conner's Teacher Rating Scale -Revised: Short Form and Conner's Parent Rating
      Scale-Revised: Short Form, and other measures of social adjustment and side
      effects. Results showed significant reductions in the core ADHD symptoms, which
      did not differ between the two treatment groups. Compared to the IR MPH group,
      the OROS MPH group showed a significantly greater slope of reductions in ADHD
      symptoms and decline in the severity of problems at school, and with peers and
      parents over time. There was no difference in rates of side effect profile
      between the two groups. Our findings suggest that OROS MPH is superior over IR
      MPH in the greater magnitude of improvement over study period without increased
      side effects in the Chinese population.

PMID- 16958570
TI  - Chronic versus episodic irritability in youth: a community-based, longitudinal
      study of clinical and diagnostic associations.
AB  - OBJECTIVE: Irritability is both a normal developmental phenomenon and a common
      psychiatric symptom in children. In psychiatric nosology, a distinction is made
      between chronic and episodic irritability. This study examines the validity of
      this distinction. METHODS: A sample of 776 youths received Diagnostic and
      Statistical Manual of Mental Disorders (DSM)-based structured interviews at three
      time points. Questions regarding episodic and chronic irritability were used to
      create scales measuring these constructs; associations with age, gender, and
      diagnosis were examined. RESULTS: Episodic and chronic irritability differed in
      their associations with age. The longitudinal stability within irritability type
      was stronger than between types. In longitudinal analyses, chronic irritability
      at time 1 (mean age 13.8 +/- 2.6 years) predicted attention deficit/
      hyperactivity disorder at time 2 (mean age 16.2 +/- 2.8 years) and major
      depression at time 3 (mean age 22.1 +/- 2.7 years). Episodic irritability at time
      1 predicted simple phobia and mania at time 2. CONCLUSIONS: Episodic and chronic
      irritability in adolescents appear to be stable, distinct constructs. Further
      research is needed to elucidate the longitudinal associations of each with
      specific psychiatric diagnoses.

PMID- 16958571
TI  - The prevalence and use of antidepressant medication in pediatric cancer patients.
AB  - BACKGROUND: During the period of cancer diagnosis and active treatment, several
      small case series have revealed high rates of psychiatric difficulty in pediatric
      patients. However, due to the methodological limitations in these studies, it
      remains impossible to determine accurately the true prevalence of mood disorders
      in pediatric cancer patients receiving cancer treatment. To date, no study has
      reported rates of antidepressant treatment in this population. OBJECTIVES: The
      aims of this study were: (1) To determine the prevalence of the use of
      antidepressant medication (ADM) in children with cancer; (2) to identify a group
      of children being treated for cancer, that are likely to receive ADM, and who
      therefore may be eligible for a prospective observational or interventional
      clinical trial of depression during cancer therapy. METHODS: We reviewed the
      medical records of 224 pediatric patients suspected for cancer in 2003 at the
      Children's Medical Center of Dallas. Of these, 6 proved non-oncologic and 2 were
      lost to follow up, leaving 216 charts for review. RESULTS: Within 1 year of
      diagnosis, 29 patients (13%) had received a psychiatric consultation. Twenty-two
      patients (10.2%) received ADM within 1 year of cancer diagnosis. Children >/= 12
      years, children with acute lymphoblastic leukemia, and children receiving
      radiotherapy or opiate analgesics were more likely to receive ADM by multivariate
      analysis. Race, sex, bone marrow transplant, and surgery were not significantly
      associated with ADM use. CONCLUSIONS: The prevalence of ADM use in pediatric
      cancer patients (10.2%) was higher than the reported rates of depression (4-8%)
      and ADM treatment (1%) in the general pediatric population. Teenagers and those
      who received opiate analgesic medications during their cancer therapy represent a
      subgroup of children in whom further study of depression and cancer therapy may
      be valuable.

PMID- 16958572
TI  - Psychotropic drug use with European American and American Indian children in
      foster care.
AB  - This study examines the use of psychotropic drugs with 473 European American and
      American Indian children in foster care. Prescription data for seven categories
      of psychotropic drugs were obtained from Medical Assistance records for the year
      2000. European American and American Indian children constituted 60% and 33% of
      the sample, respectively. Forty-three percent of the children received
      psychotropic medication. Usage among males was higher than females (45% vs. 35%).
      For children under the age of 8 usage ranged from 2% to 30%; more than 50% of the
      older children were medicated. Most frequently used drugs were antidepressants
      and stimulants. Proportionately more European American children received drugs
      than American Indian children (48% vs. 34%), but usage of different categories of
      psychotropic across racial groups was similar. The authors discuss tentative
      hypotheses for differences between the present and previous studies as well as
      for the disproportionate use of psychotropic drugs across racial groups.

PMID- 16958573
TI  - An exploratory factor analysis of the children's depression rating scale-revised.
AB  - An exploratory factor analysis was performed in a clinical sample of 314 children
      and adolescents to investigate the factor structure of the Children's Depression
      Rating Scale-Revised (CDRS-R; Poznanski et al. 1984). A maximum likelihood method
      followed by a Promax rotation yielded five factors: observed depressive mood,
      anhedonia, morbid thoughts, somatic symptoms and reported depressive mood. The
      age group and gender differences on the factors scores are evaluated. After
      controlling for gender, the adolescents had more severe depression in terms of
      observed depressive mood, anhedonia, and somatic symptoms. After controlling for
      age groups, girls had higher scores for reported depressive mood.

PMID- 16958574
TI  - The treatment of psychogenic polydipsia with risperidone in two children
      diagnosed with schizophrenia.
AB  - Polydipsia is a well-known phenomenon in adult psychiatry, but the literature
      regarding children is very limited. Just as the pathogenesis remains poorly
      understood, so does its management remain a clinical challenge. Data regarding
      the effect of risperidone on polydipsia are contradictory. We present case
      studies of remission of severe polydipsia with risperidone in two children.

PMID- 16958576
TI  - Advanced pediatric psychopharmacology.

PMID- 16958577
TI  - Two giant steps forward.

PMID- 16958578
TI  - A pilot study of aripiprazole in children and adolescents with Tourette's
      disorder.

PMID- 16958579
TI  - Attention-deficit/hyperactivity disorder, stimulants, statistics, and
      methodology.

PMID- 16958581
TI  - Activin a release into cerebrospinal fluid in a subset of patients with severe
      traumatic brain injury.
AB  - Activin A is a member of the transforming growth factor-beta superfamily and has
      been demonstrated to be elevated during inflammation and to have neuroprotective
      properties following neural insults. In this study, we examined whether traumatic
      brain injury (TBI) induced a response in activin A or in the concentrations of
      its binding protein, follistatin. Thirty-nine patients with severe TBI had daily,
      matched cerebrospinal fluid (CSF) and serum samples collected post-TBI and these
      were assayed for activin A and follistatin using specific immunoassays.
      Concentrations of both molecules were assessed relative to a variety of clinical
      parameters, such as the Glasgow Coma Score, computer tomography classification of
      TBI, measurement of injury markers, cell metabolism and membrane breakdown
      products. In about half of the patients, there was a notable increase in CSF
      activin A concentrations in the first few days post-TBI. There were only minor
      perturbations in either serum activin or in either CSF or serum follistatin
      concentrations. The CSF activin A response was not related to any of the common
      TBI indices, but was strongly correlated with two common markers of brain damage,
      neuronal specific enolase and S100-beta. Further, activin A levels were also
      associated with indices of metabolism, such as lactate and pyruvate,
      excitotoxicity (glutamate) and membrane lipid breakdown products such as
      glycerol. In one of the two patients who developed a CSF infection, activin A
      concentrations in CSF became markedly elevated. Thus, some TBI patients have an
      early release of activin A into the CSF that may result from activation of
      inflammatory and/or neuroprotective pathways.

PMID- 16958582
TI  - Adjustment for strong predictors of outcome in traumatic brain injury trials: 25%
      reduction in sample size requirements in the IMPACT study.
AB  - The aim of this study was to quantify the potential reduction in sample size that
      can be achieved by adjustment for predictors of outcome in traumatic brain injury
      (TBI) trials. We used individual patient data from seven therapeutic phase III
      randomized clinical trials (RCTs; n = 6166) in moderate or severe TBI, and three
      TBI surveys (n = 2238). The primary outcome was the dichotomized Glasgow Outcome
      Scale at 6 months (favorable/unfavorable). Baseline predictors of outcome
      considered were age, motor score, pupillary reactivity, computed tomography (CT)
      classification, traumatic subarachnoid hemorrhage, hypoxia, hypotension,
      glycemia, and hemoglobin. We calculated the potential sample size reduction
      obtained by adjustment of a hypothetical treatment effect for one to seven
      predictors with logistic regression models. The distribution of predictors was
      more heterogeneous in surveys than in trials. Adjustment of the treatment effect
      for the strongest predictors (age, motor score, and pupillary reactivity) yielded
      a reduction in sample size of 16-23% in RCTs and 28-35% in surveys. Adjustment
      for seven predictors yielded a reduction of about 25% in most studies: 20-28% in
      RCTs and 32-39% in surveys. A major reduction in sample size can be obtained with
      covariate adjustment in TBI trials. Covariate adjustment for strong predictors
      should be incorporated in the analysis of future TBI trials.

PMID- 16958583
TI  - Neuronal response to high rate shear deformation depends on heterogeneity of the
      local strain field.
AB  - Many cellular models of traumatic brain injury (TBI) deform cells in a planar (2
      D) configuration, a contrast from the three-dimensional (3-D) architecture of the
      brain, resulting in strain fields that may fail to represent the complex
      deformation patterns seen in vivo. Cells cultured in 3-D may more accurately
      represent in vivo cellular behavior than planar models due to differences in
      cytostructure, cell-cell/cell-matrix interactions and access to trophic factors;
      however, the effects of culture configuration on the response to high rate
      deformation have not been evaluated. We examined cell viability following a
      defined mechanical insult to primary cortical neurons distributed throughout a
      bioactive matrix (3-D) or in a monolayer sandwiched between layers of a bioactive
      matrix (2-D). After high rate loading (20 or 30 sec(1); 0.50 strain), there was a
      significant decrease in neuron viability for both configurations versus unloaded
      control cultures; however, neurons in 3-D presented greater cell death based on
      matched bulk loading parameters. Computer simulations of bulk loading predicted
      local cellular strains, revealing that neurons in 3-D were subjected to a
      heterogeneous strain field simultaneously consisting of tensile, compressive and
      shear strains; conversely, neurons in 2-D experienced a less complex deformation
      regime varying mainly based on shear strains. These results show differential
      susceptibility to mechanical loading between neurons cultured in 2-D and 3-D that
      may be due to differences in cellular strain manifestation. Models of TBI that
      accurately represent the related cellular biomechanics and pathophysiology are
      important for the elucidation of cellular tolerances and the development of
      mechanistically driven intervention strategies.

PMID- 16958584
TI  - Inbred mouse strains as a tool to analyze hippocampal neuronal loss after brain
      injury: a stereological study.
AB  - Traumatic brain injury (TBI) damages the hippocampus both in experimental animal
      models and in humans. In particular, the mechanical injury in combination with
      the genetic susceptibility to injury may result in neuronal loss from the
      hippocampus. This report explores the time-course of neuronal loss in the four
      primary subregions of the mouse hippocampus after a lateral fluid percussion
      injury (FPI) to the brain, and how subtle genetic differences between C57BL/6J
      and C57BL/10J mouse strains influence the extent and time course of neuronal
      loss. Using design-based stereological procedures, our results indicate
      negligible neuronal loss ipsilateral to the injury at 2 days postinjury in
      C57BL/6J mice, whereas a significant number (30-40%) of neurons are lost across
      all subregions of the hippocampus (dentate, hilus, area CA3, and area CA1) by 1
      week, which does not appear to progress at 1 month, compared to sham.
      Additionally, neuronal counts after lateral FPI in a genetically similar, yet
      kainic acid-sensitive, mouse strain (C57BL/10J) showed no statistically
      significant differences in neuron number compared to the C57BL/6J strain in
      response to brain injury. Hippocampal neuronal loss after lateral FPI and its
      consequent circuit disruption may depend more on factors related to the mechanics
      and secondary consequences of the injury, as opposed to subtle genetic variations
      between inbred mouse strains. The loss of neurons appears to be restricted to the
      first week post-injury, and the remaining neurons may serve as a substrate for
      recovery.

PMID- 16958585
TI  - Response of the contralateral hippocampus to lateral fluid percussion brain
      injury.
AB  - Traumatic brain injury is a leading cause of death and disability in the United
      States. Pathological examinations of humans and animal models after brain injury
      demonstrate hippocampal neuronal damage, which may contribute to cognitive
      impairments. Data from our laboratories have shown that, at 1 week after brain
      injury, mice possess significantly fewer neurons in all ipsilateral hippocampal
      subregions and a cognitive impairment. Since cognitive function is distributed
      across both cerebral hemispheres, the present paper explores the morphological
      and physiological response of the contralateral hippocampus to lateral brain
      injury. We analyzed the contralateral hippocampus using design-based stereology,
      Fluoro-Jade (FJ) histochemistry, and extracellular field recordings in mice at 7
      and 30 days after lateral fluid percussion injury (FPI). At 7 days, all
      contralateral hippocampal subregions possess significantly fewer healthy neurons
      compared to sham-injured animals and demonstrate FJ-positive neuronal damage, but
      not at 30 days. Both the ipsilateral and contralateral dentate gyri demonstrate
      significantly increased excitability at 7 days post-injury, but only ipsilateral
      dentate gyrus hyperexcitability persists at 30 days compared to sham. In the
      contralateral hippocampus, the transient decrease in the number of healthy
      neurons, concomitant with FJ damage, and electrophysiological alterations
      establish a stunned period of cellular and circuit dysfunction. The return of
      healthy neuron number, absence of FJ damage, and sham level of excitability in
      the contralateral hippocampus suggest recovery of structure and function by 30
      days after injury. The cognitive recovery observed after human traumatic brain
      injury may stem from a differential injury exposure and time course of recovery
      between homologous regions of the two hemispheres.

PMID- 16958586
TI  - Neuroprotection by selective inhibition of inducible nitric oxide synthase after
      experimental brain contusion.
AB  - The inflammatory response is thought to be important for secondary damage
      following traumatic brain injury (TBI). The inducible nitric oxide synthase
      (iNOS) isoform is a mediator in inflammatory reactions and may catalyze
      substantial synthesis of NO in the injured brain. This study was undertaken to
      analyze neuronal degeneration and survival, cellular apoptosis and formation of
      nitrotyrosine following treatment with the iNOS-inhibitor L-N-iminoethyl-lysine
      (L-NIL) in a model of brain contusion. A brain contusion was produced using a
      weight-drop device in 30 rats. The animals received treatment with L-NIL or NaCl
      at 15 min and 12 h after the injury and were sacrificed at 24 h or 6 days after
      trauma. iNOS activity was measured at 24 h post-trauma by the conversion of L-[U-
      ( 14 )C]arginine to L-[U-( 14 )C]citrulline and immunohistochemistry for iNOS.
      Peroxynitrite formation was indirectly assessed by nitrotyrosine (NT)
      immunohistochemistry. Neuronal degeneration and survival were assessed by Fluoro
      Jade (FJ) and NeuN stainings, and cellular death by TUNEL staining. iNOS activity
      but not iNOS immunoreactivity was significantly reduced in animals that received
      L-NIL. Neuronal degeneration (FJ) and NT immunoreactivity were significantly
      reduced at 24 h. Neuronal survival was unchanged at 24 h but increased at 6 days
      in L-NIL-treated animals. Cellular apoptosis of ED-1 and NeuN positive cells was
      significantly reduced following L-NIL treatment at 6 days after trauma. We
      demonstrated neuroprotection by selective inhibition of iNOS after trauma. L-NIL
      appeared to protect the injured brain by limiting peroxynitrite formation. Our
      findings support a putative harmful role of iNOS induction early after TBI.

PMID- 16958587
TI  - Therapeutic effect of hypothermia and dizocilpine maleate on traumatic brain
      injury in neonatal rats.
AB  - This study was undertaken to evaluate the therapeutic effect of hypothermia and
      dizocilpine maleate in traumatic brain injury (TBI) on newborn rats. After
      induction of TBI, physiologic and histopathological assessments were performed on
      both the control and therapeutic groups to evaluate the effects of both agents.
      Rats were assigned into four groups as follows: normothermic (n = 23),
      hypothermic (n = 18), normothermia plus dizocilpine maleate (n = 18) and
      hypothermia plus dizocilpine maleate (n = 18). All the rats were injured using a
      weight-drop head injury model, artificially ventilated with a 33% O(2) and 66%
      NO(2) mixture, and physiological parameters, intracranial pressure, and brain and
      rectal temperatures were recorded. Mortality, physiological, neurological
      parameters, and histopathological changes were assessed after 24 h. As a result,
      intracranial pressure, cerebral perfusion pressure, morbidity, weight loss, and
      microscopic changes were significantly worse in the normothermic group (p <0.05).
      There was no statistical difference between other groups (p > 0.05). Hypothermia
      and dizocilpine maleate displayed similar neuroprotective effects in TBI on
      newborn rats, but no additive effect was observed.

PMID- 16958588
TI  - Simvastatin promotes neurite outgrowth in the presence of inhibitory molecules
      found in central nervous system injury.
AB  - Statins (3-hydroxy-3-methylglutaryl-CoA [HMG-CoA] reductase inhibitors) inhibit
      the rate-limiting step in the mevalonate pathway, conversion of HMG-CoA to
      mevalonate, by competitive inhibition with the enzyme HMG-CoA reductase. Statins
      not only lower cholesterol levels, but are also thought to exert neuroprotective
      and neurogenic effects that may be beneficial in treating brain and spinal cord
      injuries. Data presented here illustrate that simvastatin enables neurite
      outgrowth in the presence of growth-inhibitory molecules commonly found at
      central nervous system (CNS) injury sites. To assess the effect of simvastatin on
      neurite outgrowth in the presence of inhibitory molecules present at CNS injury
      sites, rat embryonic cortex explants or postnatal spinal cord explants were grown
      on membrane filters prepared with alternating stripes of laminin and
      myelin/laminin. Immunostaining indicated that myelin stripes contain myelin
      associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgp), and
      Nogo, but do not contain chondroitin sulfate proteoglycan (CSPG). When control
      explants were grown in the presence of alternating stripes, neurite outgrowth
      preferentially extended in regions containing laminin only. In contrast, neurite
      outgrowth from explants grown in the presence of simvastatin was significantly
      less selective for laminin regions and was able to extend into regions containing
      myelin (p < 0.01). Simvastatin-induced effects were reversed by addition of
      mevalonate. Isoprenyl transferase inhibitors GGTI-286 and FTI-277, inhibitors of
      biochemical steps subsequent to HMG-CoA conversion to mevalonate, mimicked
      simvastatin- induced effects. These data suggest that simvastatin counteracts
      myelin-associated neurite outgrowth inhibition signals via mevalonate pathway
      inhibition, and may be beneficial in promoting axon regeneration in brain and
      spinal cord injury.

PMID- 16958593
TI  - Point-of-care testing--can we move from anecdote to evidence?

PMID- 16958589
TI  - Transplantation of bone marrow stem cells as well as mobilization by granulocyte
      colony stimulating factor promotes recovery after spinal cord injury in rats.
AB  - Emerging clinical studies of treating brain and spinal cord injury (SCI) with
      autologous adult stem cells led us to compare the effect of an intravenous
      injection of mesenchymal stem cells (MSCs), an injection of a freshly prepared
      mononuclear fraction of bone marrow cells (BMCs) or bone marrow cell mobilization
      induced by granulocyte colony stimulating factor (G-CSF) in rats with a balloon-
      induced spinal cord compression lesion. MSCs were isolated from rat bone marrow
      by their adherence to plastic, labeled with iron-oxide nanoparticles and expanded
      in vitro. Seven days after injury, rats received an intravenous injection of MSCs
      or BMCs or a subcutaneous injection of GCSF (from day 7 to 11 post-injury).
      Functional status was assessed weekly for 5 weeks after SCI, using the Basso
      Beattie-Bresnehan (BBB) locomotor rating score and the plantar test. Animals with
      SCI treated with MSCs, BMCs, or G-CSF had higher BBB scores and better recovery
      of hind limb sensitivity than controls injected with saline. Morphometric
      measurements showed an increase in the spared white matter. MR images of the
      spinal cords were taken ex vivo 5 weeks after SCI using a Bruker 4.7-T
      spectrometer. The lesions populated by grafted MSCs appeared as dark hypointense
      areas. Histology confirmed a large number of iron-containing and PKH 26-positive
      cells in the lesion site. We conclude that treatment with three different bone
      marrow cell populations had a positive effect on behavioral outcome and
      histopathological assessment after SCI, which was most pronounced after MSC
      injection.

PMID- 16958594
TI  - A long and winding road: defining the biological role and clinical importance of
      paraoxonases.
AB  - Paraoxonase-1 (PON1) is an enzyme belonging to a three-member gene family, each
      of which is highly conserved in mammalian evolution. Whilst there is consensus
      that the paraoxonase family members have a general protective influence, their
      precise biological role has remained elusive. A toxicological role, protecting
      from environmental poisoning by organophosphate derivatives, drove much of the
      earlier work on the enzymes. More recently, clinical interest has focused on a
      protective role in vascular disease via a hypothesised impact on lipoprotein
      lipid oxidation. Recent confirmation that the primary activity of the
      paraoxonases is that of a lactonase considerably expands the potential sources of
      biological substrates for the enzyme. Studies on such substrates may shed further
      light on different mechanisms by which paraoxonases beneficially influence
      atherosclerosis, as well as defining possible roles in limiting bacterial
      infection and in innate immunity.

PMID- 16958595
TI  - Point-of-care testing in the cardiovascular operating theatre.
AB  - Point-of-care testing (POCT) remains under scrutiny by healthcare professionals
      because of its ill-tried, young history. POCT methods are being developed by a
      few major equipment companies based on rapid progress in informatics and
      nanotechnology. Issues as POCT quality control, comparability with standard
      laboratory procedures, standardisation, traceability and round robin testing are
      being left to hospitals. As a result, the clinical and operational benefits of
      POCT were first evident for patients on the operating table. For the management
      of cardiovascular surgery patients, POCT technology is an indispensable aid.
      Improvement of the technology has meant that clinical laboratory pathologists now
      recognise the need for POCT beyond their high-throughput areas.

PMID- 16958596
TI  - Low-density lipoprotein receptor-related protein 5 and vitamin D receptor gene
      polymorphisms in relation to vitamin D levels in menopause.
AB  - BACKGROUND: The low-density lipoprotein receptor-related protein 5 (LRP5) gene
      has been recently identified as a novel candidate for osteoporosis. The c.4037C>T
      polymorphism in the LRP5 gene has been associated with bone mass variance in
      general population. In contrast, the IVS8+443G>A polymorphism in the vitamin D
      receptor gene (VDR) has not been investigated in relation to bone metabolism. The
      aim of the present study was to determine VDR IVS8+443G>A and LRP5 c.4037C>T
      polymorphisms in a cohort of 165 perimenopausal women and to associate the
      genotypes with biochemical and densitometric bone parameters in a subset of 112
      postmenopausal women. METHODS: Both polymorphisms were assessed by restriction
      analysis of the PCR product. Calcium, parathyroid hormone, vitamin D metabolites
      and bone mineral density (BMD, g/cm(2)) at the hip and in the spine (L(1)-L(4))
      were examined. RESULTS: The genotype frequencies of both IVS8+443G>A (UU 75.2%,
      Uu 23%, uu 1.8%) and c.4037C>T (CC 73.9% TC 23.6%, TT 2.4%) were comparable to
      other Caucasian female cohorts. Serum 25OH vitamin D levels, assessed in only 63
      probands, were significantly associated with VDR genotypes (ANCOVA, p<or=0.0027).
      We did not find any associations between LRP5 genotypes and bone or hormonal
      characteristics. CONCLUSIONS: VDR IVS8+443G>A polymorphism was significantly
      associated with circulating 25OH vitamin D in postmenopausal Caucasian women. The
      role of candidate gene polymorphisms in the vitamin D metabolic pathway requires
      further investigation.

PMID- 16958597
TI  - The methylenetetrahydrofolate reductase C677T gene mutation is associated with
      hyperhomocysteinemia, cardiovascular disease and plasma B-type natriuretic
      peptide levels in Korea.
AB  - BACKGROUND: Hyperhomocysteinemia is known to be a risk factor for cardiovascular
      diseases and is associated with a common mutation in the 5,10
      methylenetetrahydrofolate reductase (MTHFR) gene (677 C>T). The aims of this
      study were to confirm: 1) the association between the MTHFR C677T mutation and
      plasma homocysteine (Hcy) levels; 2) the MTHFR C677T mutation as a risk factor;
      3) the association of the MTHFR C677T mutation and plasma B-type natriuretic
      peptide (BNP) levels; and 4) the correlation between Hcy and BNP levels in
      cardiovascular diseases. METHODS: A total of 227 patients for whom BNP was
      measured were enrolled in this study. Laboratory parameters included BNP,
      creatine kinase (CK), the myocardial isoenzyme of CK (CK-MB), troponin I (TnI),
      Hcy, C-reactive protein (CRP), lactate dehydrogenase (LDH), creatinine and
      folate. The MTHFR genotype was evaluated by polymerase chain reaction (PCR) and
      restriction fragment length polymorphism (RFLP) was shown by an electrophoretic
      technique. RESULTS: The prevalence of TT homozygotes was significantly higher in
      patients with cardiovascular diseases than in patients without cardiovascular
      diseases (p=0.0001). Patients homozygous for the TT mutation had the highest
      plasma Hcy levels compared with wild-type CC homozygotes and CT mutant
      heterozygotes (p=0.0001). Plasma BNP concentrations were significantly higher in
      patients with MTHFR C677T mutation compared to patients without the mutation
      (p<0.05). Plasma BNP concentrations were positively correlated with Hcy
      concentrations (r=0.196, p<0.001). Multivariate logistic regression analysis
      showed that elevated concentrations of BNP, CRP, Hcy and the presence of the
      MTHFR C677T mutation independently contributed to the prediction of
      cardiovascular diseases. CONCLUSIONS: In cardiovascular diseases, the MTHFR C677T
      mutation: 1) is associated with plasma Hcy levels; 2) is an independent risk
      factor for cardiovascular diseases, 3) is associated with plasma BNP levels, and
      4) plasma Hcy levels are positively correlated with plasma BNP levels.

PMID- 16958598
TI  - Exploring allelic imbalance within paraffin-embedded tumor biopsies using
      pyrosequencing technology.
AB  - BACKGROUND: The comparison of molecular genetic changes in healthy and
      pathological tissues has historically led to the identification of oncogenes and
      tumor suppressor genes. It is very common that studies investigating loss of
      heterozygosity are carried out retrospectively on paraffin-embedded samples.
      METHODS: In this study, we evaluated the power of pyrosequencing for determining
      the loss of heterozygotic regions. The present method uses the fact that
      pyrosequencing is an accurate, sensitive and reproducible technique. The method
      is also simple to perform, with results available in 96-well format, making the
      assays amenable to automation. Thus, we analyzed nine single nucleotide
      polymorphisms along 1 Mb between the EMSY and PAK1 genes on 11q13, a region
      frequently rearranged in different tumors and cell lines. We assessed the study
      using samples from breast cancer and thyroid cancer biopsies. RESULTS AND
      CONCLUSIONS: We conclude that this technique is capable of detecting variations
      of >10% in allele loss. However, strong allele imbalances were detected,
      depending on the origin of the sample. Seven out of the nine markers used
      exhibited differential allele amplification, depending on the DNA quality
      (p<0.01).

PMID- 16958599
TI  - Detection of circulating tumour cells in blood by quantitative real-time RT-PCR:
      effect of pre-analytical time.
AB  - BACKGROUND: We and others have recently explored the use of quantitative real
      time RT-PCR analysis for the detection of circulating tumour cells in blood of
      patients with breast cancer (BC). One major problem in these experiments is the
      in vitro instability of the cellular RNA. The copy number of mRNA can change
      during storage and transport at room temperature and this may hamper accurate
      quantitative measurements of specific transcripts, especially when working with
      small numbers of target mRNAs. METHODS: Peripheral blood samples were obtained
      from two healthy volunteers and 13 patients with BC. Blood was stored at room
      temperature for 0, 1, 2, 4, 6, 24, 48 and 72 h. The potential alteration of gene
      expression for six target genes was investigated by quantitative real-time RT
      PCR. RESULTS: For beta-actin, GAPDH, cytokeratin-19 (CK-19) and HER2, a
      significant decrease in expression level occurs after 4 h (CK-19 and HER2), 6 h
      (beta-actin) or 24 h (GAPDH). Mammaglobin expression was only measurable in two
      samples and seems to be stable for at least 6 h. For vascular endothelial growth
      factor (VEGF), a statistically significant increase in expression level is
      observed in samples processed 24 h after collection. CONCLUSIONS: Most
      transcripts were reduced in samples that were stored overnight at room
      temperature compared with fresh samples, but upregulation of transcripts,
      probably as an active response to cellular stress, also occurs when blood is
      removed from its in vivo environment and stored ex vivo. Optimally, blood samples
      and RNA should be processed or stabilised within 3 h after collection to avoid
      interference of the in vivo gene expression signature by ex vivo stress
      responses.

PMID- 16958600
TI  - Hereditary hyper-ACE-emia due to the Pro1199Leu mutation of somatic ACE as a
      potential pitfall in diagnosis: a first family outside Europe.
AB  - Elevated plasma levels of angiotensin converting enzyme (ACE) are associated with
      granulomatous diseases. However, several families of autosomal dominant hyper-ACE
      emia without disease association have already been reported. Recently, the ACE
      mutation c.3705C>T (Pro1199Leu) was identified as the genetic correlate in
      European cases of asymptomatic autosomal dominant hyper-ACE-emia. Here, we
      describe a first family outside Europe with asymptomatic autosomal-dominant hyper
      ACE-emia due to the ACE Pro1199Leu mutation. Benign autosomal-dominant hyper-ACE
      emia should be considered for differential diagnosis of elevated ACE levels
      worldwide.

PMID- 16958601
TI  - Molecular assay for detection of the common carnitine palmitoyltransferase 1A
      1436(C>T) mutation.
AB  - BACKGROUND: Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a metabolic
      disorder that occurs at a key checkpoint of fatty acid metabolism. A new form of
      CPT1A deficiency caused by a mutation at nucleotide 1436 (C>T), resulting in an
      amino acid substitution of leucine for proline at position 479 (P479L), has been
      isolated in Canadian First Nations and Inuit populations. The present study
      offers a molecular method for assessing CPT1A 1436 (C>T) mutation status.
      METHODS: CPT1A-deficient fibroblasts from four patient fibroblast cell lines and
      ten patient peripheral blood spots were all analyzed by polymerase chain reaction
      (PCR) coupled to restriction endonuclease (RE) treatment. Genomic DNA was PCR
      amplified and treated with an RE specific for normal DNA. CPT1A 1436 (C>T)
      mutations were identified by resistance to RE treatment. RESULTS: The RE-PCR
      assay identified homozygosity for the 1436 (C>T) mutation in four fibroblast cell
      lines and nine blood spots with CPT1A enzyme deficiency. In addition, the assay
      identified one blood spot that corresponded to the heterozygous genotype.
      CONCLUSIONS: RE-PCR assay for the 1436 (C>T) mutation provides a rapid assay for
      the diagnosis of CPT1A deficiency resulting from this mutation. The assay will
      have utility in screening populations with a high prevalence of this genotype.

PMID- 16958602
TI  - Serum cytokine levels and the expression of estrogen and progesterone receptors
      in breast cancer patients.
AB  - BACKGROUND: The aim of this study was to assess the correlation between serum
      concentrations of cytokines and soluble cytokine receptors in breast cancer
      patients and the expression of estrogen and progesterone receptors in tumor
      cells. METHODS: The study comprised 158 female breast cancer patients before
      treatment and 50 healthy individuals as a reference group. RESULTS: The study
      revealed significantly higher concentrations of most cytokines in breast cancer
      patients compared to the reference group. Assessment of the correlation between
      cytokine concentrations in serum and the expression of estrogen and progesterone
      receptors in tumor cells showed significantly higher interleukin-8 (IL-8)
      concentrations in patients lacking progesterone receptors in comparison to
      patients with these receptors. The concentrations of cytokines and their soluble
      receptors as a function of the expression of estrogen and progesterone receptors
      were also analyzed in two age groups. In younger patients, aged 50 years and
      below, no significant differences were found between serum cytokine
      concentrations and the expression of both estrogen and progesterone receptors. In
      patients older than 50 years, significantly higher IL-8 concentrations were
      observed in individuals lacking progesterone receptors, whereas IL-1ra was
      significantly higher in those lacking estrogen receptors. CONCLUSIONS: IL-1ra and
      IL-8 concentrations in serum, together with a lack of estrogen and progesterone
      receptors in tumor cells, in breast cancer patients older than 50 years could
      represent additional predictive factors for this disease.

PMID- 16958603
TI  - Protein Z levels and prognosis in patients with acute coronary syndromes.
AB  - BACKGROUND: Protein Z, a vitamin K-dependent glycoprotein, serves as a cofactor
      for the inhibition of activated coagulation factor X. During recent years, a role
      for low levels of protein Z in prothrombotic disorders such as ischemic stroke
      and acute coronary syndromes (ACS) has been reported. The aims of this study were
      to test changes in protein Z and their association with outcome at 1-year follow
      up in 193 (150 male, 43 female) patients with ACS. RESULTS: Protein Z plasma
      levels were significantly lower (p<0.0001) after 1 year [1,600 (28-3,736) ng/mL]
      compared to the baseline [1,695 (294-4,068) ng/mL]. Regression analysis showed a
      significant association between baseline protein Z below the 5th percentile of
      our control group and subsequent adverse cardiac events at follow-up (odds ratio
      3.3; 95% CI 1.04-10.7; p=0.04). Moreover, Cox regression analysis showed that low
      protein Z levels at admission were significant predictors of major adverse
      cardiac events (cardiac death, non-fatal recurrent myocardial infarction, and
      need for target lesion revascularization) after 1 year (hazard risk 2.5; 95% CI
      1.02-6.5, p=0.04). CONCLUSIONS: Our results show that in patients with ACS: 1)
      protein Z decreases moving from the acute to the convalescent phase; and 2) low
      levels of baseline protein Z are significantly associated with adverse outcome at
      1-year follow-up.

PMID- 16958604
TI  - Determination of total bilirubin in whole blood from neonates: results from a
      French multicenter study.
AB  - BACKGROUND: Jaundice is frequent in neonates and can cause severe complications,
      especially in premature neonates, particularly the risk of developing acute
      bilirubin encephalopathy. Our purpose was to verify if determination of total
      bilirubin (TBIL) in whole blood on an ABL 735 blood gas analyzer with a
      spectrophotometer module could provide an analytical alternative to chemical
      methods of TBIL measurement. METHODS: Our multicenter comparative study involved
      four hospital laboratories. We studied the repeatability and reproducibility of
      ABL 735 TBIL measurements in two control sera of medium (N1, 58.1 micromol/L) and
      high (N2, 275.3 micromol/L) TBIL levels. The same study was simultaneously
      conducted on four chemistry instruments (two LX 20, one Integra 800 and one
      Hitachi 917) using four Jendrassik-Grof derived methods. At one site,
      repeatability was performed with two adult whole-blood samples containing low and
      high TBIL levels (55.1 and 312.6 micromol/L). RESULTS: Repeatability tests
      provided coefficients of variation (CVs) between 0.67% and 1.86% on the ABL 735
      system, vs. 0.35% and 1.96% for the chemistry instruments. Reproducibility tests
      for the same control sera resulted in CVs between 1.01% and 3.55% for the ABL 735
      and between 0.52% and 3.65% for the chemistry instruments. Recovery for the N1
      and N2 control sera was 102-120%. A correlation study of TBIL determination in
      whole blood vs. plasma was conducted on 473 neonatal blood samples. Correlation
      coefficients between whole blood and plasma TBIL ranged from 0.969 to 0.994.
      Passing-Bablok equations were y=1.17x+9.7 [site 1 (IP)], y=1.01x+5.6 [site 2
      (JPB, MR)], and y=1.00x-20 [site 3 (AS)]. Only 10% of the results fell outside
      the 10% range in the bias-corrected Bland-Altman difference plot for the ABL 735
      method compared to traditional laboratory methods. CONCLUSIONS: The ABL 735
      instrument is reliable for measuring TBIL in 70-microL whole blood samples from
      neonates. Thus, this method might allow significant blood savings in preterm
      neonates. Correlation with the reference method for plasma or sera must be
      established to ensure good follow-up of patients.

PMID- 16958605
TI  - Analysis of protein S-100B in serum: a methodological study.
AB  - BACKGROUND: Dysfunction and damage of the human central nervous system can be
      detected with biochemical markers, and protein S-100B is the best-established
      such marker. The aim of this study was to evaluate whether the protein is stable
      during long-term storage, to establish reference values for the new Elecsys S100
      test and to compare this new method with the Liaison Sangtec 100 test. METHODS:
      We analysed blood samples from 118 blood donors and 196 patients with
      subarachnoid haemorrhage or head injury. The long-term stability of S-100B in
      frozen serum samples was evaluated with repeated analysis in 1997 and 2003 using
      an immunoradiometric assay. Method comparison between the Liaison Sangtec 100 and
      Elecsys S100 tests was performed using Bland-Altman difference plots. RESULTS:
      Serum concentrations increased significantly during long-term storage (mean
      difference 0.15 microg/L; +/-2 SD, 0.55 microg/L). Serum measurements using the
      Elecsys S100 method in 118 healthy blood donors showed S-100B levels between 0.02
      and 0.08 microg/L (mean 0.05). The 95th percentile was 0.07 microg/L. The Liaison
      Sangtec 100 test usually measured higher concentrations than the Elecsys S100
      method, and the difference between the two methods increased with increasing
      concentrations. The mean difference between the methods was 0.14 microg/L (+/-2
      SD, 0.39 microg/L). CONCLUSIONS: Protein S-100B is not stable during long-term
      storage and the two analytical methods are not interchangeable.

PMID- 16958606
TI  - Lipid peroxidation and homocysteine levels in Behcet's disease.
AB  - BACKGROUND: The aim of this study was to investigate serum paraoxonase (PON1)
      activity in relation to homocysteine, malondialdehyde (MDA) and lipid parameters
      in active and inactive Behcet's disease (BD). METHODS: A total of 46 consecutive
      BD patients and 25 healthy control subjects were included in the present study.
      RESULTS: Serum PON1 activity in both active and inactive BD was significantly
      lower compared with healthy subjects (p<0.05). When compared to the control
      group, serum MDA levels were significantly higher in both active and inactive BD
      (p<0.05). Serum C-reactive protein (CRP) and homocysteine concentrations were
      significantly higher in active BD than those in inactive BD and control subjects
      (p<0.05). In addition, there was significant negative correlation between serum
      PON1 and MDA levels (r=-0.697, p<0.05) and serum PON1 activity was also
      negatively correlated with homocysteine levels (r=-0.428, p<0.05) in BD patients.
      CONCLUSIONS: Decreased PON1 could explain the increased lipid peroxidation and
      oxidative stress observed in BD. Also, according to our results, we suggest that
      homocysteine may contribute to decreased serum PON1 activity.

PMID- 16958607
TI  - Lower expression of the alpha2,3-sialylated fibronectin glycoform and appearance
      of the asialo-fibronectin glycoform are associated with high concentrations of
      fibronectin in human seminal plasma with abnormal semen parameters.
AB  - BACKGROUND: Sialic acid isoforms expressed on glycoconjugates are known to be
      involved in different biological functions. The aim of this study was to compare
      alpha2,3- and/or alpha2,6-linked sialic acid expression on fibronectin in the
      seminal plasma of male partners from infertile couples. The data obtained were
      analyzed in relation to normal and abnormal semen parameters, as well as to
      fibronectin concentrations. METHODS: Fibronectin concentrations were determined
      by ELISA using a specific monoclonal antibody. The relative degree of sialic acid
      linked to fibronectin glycans either by alpha2,3 or alpha2,6 isomeric linkage was
      estimated by lectin-fibronectin ELISA utilizing lectins from Maackia amurensis
      and Sambucus nigra, respectively. RESULTS: High seminal fibronectin concentration
      was more frequently associated with abnormal semen parameters. The glycans of
      seminal plasma fibronectin, in contrast to blood plasma fibronectin, contained
      sialic acid more frequently attached by alpha2,3 than by alpha2,6 isomeric
      linkage. The relative amounts of both alpha2,3- and alpha2,6-linked sialic acid
      fibronectin isoforms were lower in the seminal plasma of men suspected of
      infertility. CONCLUSIONS: Seminal fibronectin showed an oncofetal type of
      sialylation and the distribution of hypo- and asialylated fibronectin glycoforms
      were associated with abnormal semen parameters and with high concentrations of
      fibronectin.

PMID- 16958608
TI  - Automated processing of whole blood samples for the determination of
      immunosuppressants by liquid chromatography tandem-mass spectrometry.
AB  - BACKGROUND: Liquid chromatography tandem-mass spectrometry (LC-MS/MS) is an
      efficient technology for routine determination of immunosuppressants in whole
      blood; however, time-consuming manual sample preparation remains a significant
      limitation of this technique. METHODS: Using a commercially available robotic
      pipetting system (Tecan Freedom EVO), we developed an automated sample
      preparation protocol for quantification of tacrolimus in whole blood by LC-MS/MS.
      Barcode reading, sample resuspension, transfer of whole blood aliquots into a
      deep-well plate, addition of internal standard solution, mixing, and protein
      precipitation by addition of an organic solvent is performed by the robotic
      system. After centrifugation of the plate, the deproteinized supernatants are
      submitted to on-line solid phase extraction, using column switching prior to LC
      MS/MS analysis. The only manual actions within the entire process are decapping
      of the tubes, and transfer of the deep-well plate from the robotic system to a
      centrifuge and finally to the HPLC autosampler. Whole blood pools were used to
      assess the reproducibility of the entire analytical system for measuring
      tacrolimus concentrations. RESULTS: A total coefficient of variation of 1.7% was
      found for the entire automated analytical process (n=40; mean tacrolimus
      concentration, 5.3 microg/L). Close agreement between tacrolimus results obtained
      after manual and automated sample preparation was observed. CONCLUSIONS: The
      analytical system described here, comprising automated protein precipitation, on
      line solid phase extraction and LC-MS/MS analysis, is convenient and precise, and
      minimizes hands-on time and the risk of mistakes in the quantification of whole
      blood immunosuppressant concentrations compared to conventional methods.

PMID- 16958609
TI  - Role of methionine residues of albumin in T-R conversion of hemoglobin.
AB  - BACKGROUND: Hemoglobin (Hb) has peroxidase (POD)-like activity. We found that the
      addition of albumin to human Hb purified from venous erythrocytes increased its
      POD-like activity. METHODS: We treated human Hb with a Blue-Toyopearl column of
      immobilized albumin, compared the treated Hb and native Hb for POD-like activity,
      the level of Hb-bound 2,3-diphosphoglycerate (2,3-DPG), and the absorption
      spectrum, and found that treatment with albumin released 2,3-DPG from Hb,
      resulting in a tense-relaxed (T-R) conversion and increased POD-like activity.
      RESULTS: The addition of human, mouse, rat, or bovine albumin to human Hb
      increased its POD-like activity. Addition of human albumin caused the highest
      increase, followed by that of mouse, rat, and bovine albumin in order. Addition
      of rabbit or guinea pig albumin caused little or no increase in the POD-like
      activity of Hb. Analysis of the distribution of methionine residues in the
      albumins of these animals showed that human, mouse, and rat albumins have a
      methionine residue at position 8 in loop 3 of domain I, and human and mouse
      albumins have an additional methionine residue in domain I. Bovine albumin has no
      methionine residue at position 8 in loop 3 of domain I, but has two methionine
      residues at other positions in domain I. Mouse and rat albumins have no
      methionine residues in domain I. CONCLUSIONS: These results suggest that the
      methionine residue at position 8 in loop 3 of domain I is most closely involved
      in the T-R conversion of human Hb. The addition of 2,3-DPG to albumin or
      selective oxidation of the methionine residues of albumin lessened the increase
      in POD-like activity when albumin was added to Hb, providing supporting evidence
      that the methionine residue of albumin is involved in the T-R conversion. The
      methionine residue of albumin may have a very important role in the degradation
      of Hb released from erythrocytes in blood vessels.

PMID- 16958610
TI  - Rheumatoid factor interference in the determination of carbohydrate antigen 19-9
      (CA 19-9).
AB  - BACKGROUND: Investigation of a 61-year-old Caucasian male suffering from fatigue
      and weight loss led to the finding of a carbohydrate antigen 19-9 (CA 19-9)
      concentration of 80 kU/L using an ADVIA Centaur analyser. Determination of CA 19
      9 on Vidas, AxSYM and Architect i2000 systems gave normal results. His rheumatoid
      factor concentration was very high (900 kIU/L) and assay interference was
      suspected. METHODS: Besides using several laboratory procedures to show the cause
      of the interference, we tried to estimate the frequency of the suspected
      interference. Therefore, two studies were performed. The first was carried out in
      a multicentre setting using four different CA 19-9 methods on 51 randomly
      selected samples with high rheumatoid factor concentrations and ten samples
      containing no or very low rheumatoid factor. In the second study we used
      heterophilic blocking tubes for 68 routinely analysed samples with CA 19-9
      concentrations ranging between 37 and 250 kU/L using an ADVIA Centaur analyser.
      RESULTS: In the multicentre study we found eight discrepant CA 19-9 results, but
      only one was clearly due to interference. We showed that the interference
      detected, just as in the index case, was caused by rheumatoid factor. The other
      discrepancies could not be explained, but are probably related to method
      dependent differences. In the 68 routinely analysed samples, no interference
      could be shown using the heterophilic blocking tubes. CONCLUSIONS: Although
      interferences in the CA 19-9 assay are not frequent, the ADVIA Centaur system
      appears to be more sensitive to rheumatoid factor interference. The lack of
      standardisation remains an important issue for this assay. The determination of
      CA 19-9 during the follow-up of patients should be performed using a single
      method. If, however, there is any clinical doubt about a result, CA 19-9 should
      be determined using another method to exclude possible interferences.

PMID- 16958611
TI  - Significance of Elecsys S100 immunoassay for real-time assessment of traumatic
      brain damage in multiple trauma patients.
AB  - BACKGROUND: The neuroprotein S100 released into the circulation has been
      suggested as a reliable marker for primary brain damage. However, safe
      identification of relevant traumatic brain injury (TBI) may possibly be hampered
      by S100 release from peripheral tissue. The objective of this study was to
      measure early S100 levels using the Elecsys S100 immunoassay for real-time
      assessment of severe TBI in multiple trauma. METHODS: Consecutively admitted
      multiple trauma patients (injury severity score >or=16 points) were stratified
      according to the results of the initial cerebral computed tomography (CCT)
      examination. S100 serum levels were determined at admission and at 6, 12, 24, 48
      and 72 h after trauma. Data were correlated to creatine phosphokinase (CK) and
      lactate dehydrogenase (LDH) serum levels. Using receiver operating characteristic
      (ROC) analysis, the discriminating power of S100 measurement was calculated for
      the detection of CCT+ findings. RESULTS: Median S100 levels of CCT+ patients
      (n=9; 37 years) decreased from 3.30 microg/L at admission to 0.41 microg/L 72 h
      after trauma. They revealed no significant differences to CCT- patients (n=18; 44
      years), but remained elevated compared to controls. Median CK and LDH levels
      correlated with the corresponding S100 levels during the first 24 h after trauma.
      ROC analysis displayed a maximum area under the curve of only 0.653 at 12 h after
      trauma. No significant difference was calculated for the differentiation between
      CCT+ and CCT- patients. CONCLUSIONS: Measurements of S100 serum levels using the
      Elecsys S100 immunoassay are not reliable for the real-time detection of severe
      TBI in multiple trauma patients. Due to soft tissue trauma or bone fractures,
      S100 is mainly released from peripheral sources such as adipocytes or skeletal
      muscle cells.

PMID- 16958613
TI  - ESEAP: the national External Quality Assessment Scheme for clinical chemistry in
      Greece and Cyprus.

PMID- 16958612
TI  - IFCC primary reference procedures for the measurement of catalytic activity
      concentrations of enzymes at 37 degrees C.
AB  - This paper is the eighth in a series dealing with reference procedures for the
      measurement of catalytic activity concentrations of enzymes at 37 degrees C and
      the certification of reference preparations. Other parts deal with: Part 1. The
      concept of reference procedures for the measurement of catalytic activity
      concentrations of enzymes; Part 2. Reference procedure for the measurement of
      catalytic concentration of creatine kinase; Part 3. Reference procedure for the
      measurement of catalytic concentration of lactate dehydrogenase; Part 4.
      Reference procedure for the measurement of catalytic concentration of alanine
      aminotransferase Part 5. Reference procedure for the measurement of catalytic
      concentration of aspartate aminotransferase Part 6. Reference procedure for the
      measurement of catalytic concentration of gamma-glutamyltransferase; Part 7.
      Certification of four reference materials for the determination of enzymatic
      activity of gamma-glutamyltransferase, lactate dehydrogenase, alanine
      aminotransferase and creatine kinase at 37 degrees C. The procedure described
      here is deduced from the previously described 30 degrees C IFCC reference method.
      Differences are tabulated and commented on.

PMID- 16958614
TI  - Evaluation of whole-genome amplification using multiple-displacement
      amplification of a limited number of cells.

PMID- 16958615
TI  - Comparison of various methods for the determination of total protein in urine.

PMID- 16958616
TI  - Description of examinations and their results and ISO standard 15189.

PMID- 16958617
TI  - Malignant hyperthermia mutation sites in the Leu2442-Pro2477 (DP4) region of RyR1
      (ryanodine receptor 1) are clustered in a structurally and functionally definable
      area.
AB  - To explain the mechanism of pathogenesis of channel disorder in MH (malignant
      hyperthermia), we have proposed a model in which tight interactions between the N
      terminal and central domains of RyR1 (ryanodine receptor 1) stabilize the closed
      state of the channel, but mutation in these domains weakens the interdomain
      interaction and destabilizes the channel. DP4 (domain peptide 4), a peptide
      corresponding to residues Leu2442-Pro2477 of the central domain, also weakens the
      domain interaction and produces MH-like channel destabilization, whereas an MH
      mutation (R2458C) in DP4 abolishes these effects. Thus DP4 and its mutants serve
      as excellent tools for structure-function studies. Other MH mutations have been
      reported in the literature involving three other amino acid residues in the DP4
      region (Arg2452, Ile2453 and Arg2454). In the present paper we investigated the
      activity of several mutants of DP4 at these three residues. The ability to
      activate ryanodine binding or to effect Ca2+ release was severely diminished for
      each of the MH mutants. Other substitutions were less effective. Structural
      studies, using NMR analysis, revealed that the peptide has two a-helical regions.
      It is apparent that the MH mutations are clustered at the C-terminal end of the
      first helix. The data in the present paper indicates that mutation of residues in
      this region disrupts the interdomain interactions that stabilize the closed state
      of the channel.

PMID- 16958618
TI  - Hypoxia-induced assembly of prolyl hydroxylase PHD3 into complexes: implications
      for its activity and susceptibility for degradation by the E3 ligase Siah2.
AB  - PHD1-3 (prolyl hydroxylases 1-3) catalyse the hydroxylation of HIF (hypoxia
      inducible factor)-alpha subunit that triggers the substrate ubiquitination and
      subsequent degradation. The RING (really interesting new gene) finger E3 ligase
      Siah2 preferentially targets PHD3 for degradation. Here, we identify the
      requirements for such selective targeting. Firstly, PHD3 lacks an N-terminal
      extension found in PHD1 and PHD2; deletion of this domain from PHD1 and PHD2
      renders them susceptible to degradation by Siah2. Secondly, PHD3 can homo- and
      hetero-multimerize with other PHDs. Consequently, PHD3 is found in high-molecular
      mass fractions that were enriched in hypoxia. Interestingly, within the lower
      molecular-mass complex, PHD3 exhibits higher specific activity towards
      hydroxylation of HIF-1alpha and co-localizes with Siah2, suggesting that Siah2
      limits the availability of the more active form of PHD3. These findings provide
      new insight into the mechanism underlying the regulation of PHD3 availability and
      activity in hypoxia by the E3 ligase Siah2.

PMID- 16958619
TI  - NMR characterization of the pH 4 beta-intermediate of the prion protein: the N
      terminal half of the protein remains unstructured and retains a high degree of
      flexibility.
AB  - Prion diseases are associated with the misfolding of the PrP (prion protein) from
      a largely alpha-helical isoform to a beta-sheet-rich oligomer. CD has shown that
      lowering the pH to 4 under mildly denaturing conditions causes recombinant PrP to
      convert from an alpha-helical protein into one that contains a high proportion of
      beta-sheet-like conformation. In the present study, we characterize this soluble
      pH 4 folding intermediate using NMR. (15)N-HSQC (heteronuclear single-quantum
      correlation) studies with mPrP (mouse PrP)-(23-231) show that a total of 150
      dispersed amide signals are resolved in the native form, whereas only 65 amide
      signals with little chemical shift dispersion are observable in the pH 4 form.
      Three-dimensional (15)N-HSQC-TOCSY and NOESY spectra indicate that the observable
      residues are all assigned to amino acids in the N-terminus: residues 23-118.
      (15)N transverse relaxation measurements indicate that these N-terminal residues
      are highly flexible with additional fast motions. These observations are
      confirmed via the use of truncated mPrP-(112-231), which shows only 16 (15)N-HSQC
      amide peaks at pH 4. The loss of signals from the C-terminus can be attributed to
      line broadening due to an increase in the molecular size of the oligomer or
      exchange broadening in a molten-globule state.

PMID- 16958621
TI  - Fatty liver is an integral feature of familial combined hyperlipidaemia:
      relationship with fat distribution and plasma lipids.
AB  - Overproduction of VLDL (very-low-density lipoprotein) particles is an important
      cause of FCHL (familial combined hyperlipidaemia). It has been shown recently
      that VLDL production is driven by the amount of hepatic fat. The present study
      was conducted to determine the prevalence of fatty liver in relation to the
      different fat compartments and lipid parameters in FCHL. A total of 68 FCHL
      patients, 110 normolipidaemic relatives and 66 spouses underwent ultrasound of
      the abdominal region to estimate the amount of subcutaneous, visceral and hepatic
      fat. Skinfold callipers were used to measure subcutaneous fat of the biceps,
      triceps, subscapular and supra-iliacal regions. Fatty liver was observed in 18%
      of the spouses, 25% of the normolipidaemic relatives and 49% of the FCHL
      patients. After adjustment for age, gender and body mass index, the prevalence of
      fatty liver was significantly higher in FCHL patients compared with spouses [OR
      (odds ratio), 3.1; P=0.03], and also in the normolipidaemic relatives compared
      with spouses (OR, 4.0; P=0.02), whereas no differences were observed between FCHL
      patients and normolipidaemic relatives (OR, 0.8; P=0.58). In the normolipidaemic
      relatives and FCHL patients combined, both visceral fat mass and subcutaneous
      abdominal fat were independent predictors of fatty liver (P<0.001 for both fat
      compartments; FCHL status corrected). Of interest, fatty liver stages were
      correlated with both VLDL-apoB (apolipoprotein B) and VLDL-triacylglycerols
      (triglycerides) in a representative subset (n=69) of patients and relatives
      (r(2)=0.12, P=0.006; and r(2)=0.18, P=0.001 respectively). These results show
      that fatty liver is a central aspect of FCHL, i.e. patients and normolipidaemic
      relatives. Both visceral and subcutaneous adiposity contribute to its 3-4-fold
      higher risk in FCHL.

PMID- 16958620
TI  - Trypanothione-dependent glyoxalase I in Trypanosoma cruzi.
AB  - The glyoxalase system, comprizing glyoxalase I and glyoxalase II, is a ubiquitous
      pathway that detoxifies highly reactive aldehydes, such as methylglyoxal, using
      glutathione as a cofactor. Recent studies of Leishmania major glyoxalase I and
      Trypanosoma brucei glyoxalase II have revealed a unique dependence upon the
      trypanosomatid thiol trypanothione as a cofactor. This difference suggests that
      the trypanothione-dependent glyoxalase system may be an attractive target for
      rational drug design against the trypanosomatid parasites. Here we describe the
      cloning, expression and kinetic characterization of glyoxalase I from Trypanosoma
      cruzi. Like L. major glyoxalase I, recombinant T. cruzi glyoxalase I showed a
      preference for nickel as its metal cofactor. In contrast with the L. major
      enzyme, T. cruzi glyoxalase I was far less fast-idious in its choice of metal
      cofactor efficiently utilizing cobalt, manganese and zinc. T. cruzi glyoxalase I
      isomerized hemithio-acetal adducts of trypanothione more than 2400 times more
      efficiently than glutathione adducts, with the methylglyoxal adducts 2-3-fold
      better substrates than the equivalent phenylglyoxal adducts. However,
      glutathionylspermidine hemithioacetal adducts were most efficiently isomerized
      and the glutathionylspermidine-based inhibitor S-4
      bromobenzylglutathionylspermidine was found to be a potent linear competitive
      inhibitor of the T. cruzi enzyme with a K(i) of 5.4+/-0.6 microM. Prediction
      algorithms, combined with subcellular fractionation, suggest that T. cruzi
      glyoxalase I localizes not only to the cytosol but also the mitochondria of T.
      cruzi epimastigotes. The contrasting substrate specificities of human and
      trypanosomatid glyoxalase enzymes, confirmed in the present study, suggest that
      the glyoxalase system may be an attractive target for anti-trypanosomal
      chemotherapy.

PMID- 16958622
TI  - Invariant Thr244 is essential for the efficient acylation step of the non
      phosphorylating glyceraldehyde-3-phosphate dehydrogenase from Streptococcus
      mutans.
AB  - One of the most striking features of several X-ray structures of CoA-independent
      ALDHs (aldehyde dehydrogenases) in complex with NAD(P) is the conformational
      flexibility of the NMN moiety. However, the fact that the rate of the acylation
      step is high in GAPN (non-phosphorylating glyceraldehyde-3-phosphate
      dehydrogenase) from Streptococcus mutans implies an optimal positioning of the
      nicotinamide ring relative to the hemithioacetal intermediate within the ternary
      GAPN complex to allow an efficient and stereospecific hydride transfer.
      Substitutions of serine for invariant Thr244 and alanine for Lys178 result in a
      drastic decrease of the efficiency of hydride transfer which becomes rate
      limiting. The crystal structure of the binary complex T244S GAPN-NADP shows that
      the absence of the beta-methyl group leads to a well-defined conformation of the
      NMN part, including the nicotinamide ring, clearly different from that depicted
      to be suitable for an efficient hydride transfer in the wild-type. The
      approximately 0.6-unit increase in pK(app) of the catalytic Cys302 observed in
      the ternary complex for both mutated GAPNs is likely to be due to a slight
      difference in positioning of the nicotinamide ring relative to Cys302 with
      respect to the wild-type ternary complex. Taken together, the data support a
      critical role of the Thr244 beta-methyl group, held in position through a
      hydrogen-bond interaction between the Thr244 beta-hydroxy group and the epsilon
      amino group of Lys178, in permitting the nicotinamide ring to adopt a
      conformation suitable for an efficient hydride transfer during the acylation step
      for all the members of the CoA-independent ALDH family.

PMID- 16958624
TI  - Echinococcus granulosus in northern Queensland. 1. Prevalence in cattle.
AB  - OBJECTIVE: To determine the prevalence and geographical distribution of
      hydatidosis and investigate factors that might be expected to influence the
      prevalence of hydatids in cattle in Queensland north of the Tropic of Capricorn.
      To determine the effect of natural levels of infection on carcase weight and
      subsequent economic loss. PROCEDURE: An abattoir survey conducted in 1981
      provided information on the distribution, prevalence and viability of hydatid
      cysts in cattle from all shires north of the Tropic of Capricorn in Queensland.
      Livers, lungs and spleens from 10,382 cattle were palpated at abattoirs in
      Cairns, Townsville and Rockhampton to detect hydatid cysts. Prevalence of
      infection in cattle in each shire was estimated from results of the abattoir
      study together with reports of infection in a further 22,185 cattle obtained from
      abattoir records. Linear modelling was used to define the effect of geographical
      origin, age, breed and sex on prevalence of infection. Differences in the weights
      of carcases between infected and non-infected cattle of the same age, sex, breed
      and property of origin were examined. The economic loss to the beef industry in
      the region surveyed was estimated. RESULTS: Cattle infected with hydatids
      originated almost entirely from regions to the east of the Great Dividing Range.
      The mean prevalence inside this zone was 28% compared with 3% in other areas.
      Viable protoscoleces were found in 0.7% of cysts. Geographical origin and age of
      the cattle were the most significant factors influencing prevalence. Infection
      with hydatids had no effect on carcase weight. Economic loss was limited to that
      associated with condemnations of organs at meat inspection, estimated to be 0.5
      million dollars per annum in 1981 and 6 million dollars in 2004. The distribution
      of hydatids in Queensland north of the Tropic of Capricorn corresponded most
      closely with the distribution of small wallabies such as Macropus dorsalis (black
      striped wallaby), M parryi (whiptail wallaby) and M rufogriseus (red-necked
      wallaby). CONCLUSIONS: It was concluded that cattle are not an important part of
      maintaining the life-cycle of E granulosus in Queensland north of the Tropic of
      Capricorn. Within the endemic zone, which is almost all to the east of the Great
      Dividing Range, the local pattern of bovine echinococcosis is most likely to be
      determined by the presence or absence of small species of wallaby such as M
      dorsalis, M parryi and M rufogriseus.

PMID- 16958625
TI  - Echinococcus granulosus in northern Queensland. 2. Ecological determinants of
      infection in beef cattle.
AB  - OBJECTIVE: To provide information on possible ecological determinants of
      infection with Echinococcus granulosus in a beef pastoral area of northern
      Queensland. PROCEDURE: An ecological study was carried out on the prevalence and
      viability of infection with Echinococcus granulosus in definitive and potential
      intermediate hosts, and their predator prey relationships. Seven adjacent
      extensive beef properties 100 km south of Townsville, that included areas of
      savannah, open woodland and dense closed scrub, were selected for the study.
      Infection with E granulosus in dingoes was determined at post mortem, and in
      domestic dogs by examining duodenal mucus after purging with arecoline
      hydrobromide. Cattle, wild pigs and macropods were examined at post mortem for
      viable hydatid cysts. The diet of dingoes was investigated by identifying the
      hair of prey species found in their stomach and colon, and that of domestic dogs
      by questioning their owners. RESULTS: Prevalence of hydatidosis in adult cattle
      ranged from 41% in animals from properties with large areas of dense closed
      scrub, to 3% on properties with little or no scrub. Hydatid cysts were found in
      21.8% of black-striped wallabies (Macropus dorsalis), 9.4% of feral pigs, 1.5% of
      wallaroos (Macropus robustus), and 1.4% of eastern grey kangaroos (Macropus
      giganteus). No rufous rat kangaroos (Aepyprymnus rufescens) or swamp wallabies
      (Wallabia bicolor) were infected. Most cysts in macropods were viable, whereas in
      pigs about half were viable and in cattle only 0.7% contained viable
      protoscoleces. Infection with E granulosus was detected in 76% of dingoes,
      whereas no infection was detected in domestic dogs in the study area.
      CONCLUSIONS: It was concluded that the sylvatic cycle of E granulosus in the
      study area was maintained mainly through predation of black-striped wallabies by
      dingoes, and that the verges of dense scrub were the main nidus of infection.

PMID- 16958626
TI  - Induction of parturition in dairy cattle and its effects on health and subsequent
      lactation and reproductive performance.
AB  - OBJECTIVE: To determine the effect of induction of parturition on health, milk
      production and reproductive performance of dairy cows. DESIGN: A prospective
      cohort study in 62 dairy herds. PROCEDURE: Health, milk production and fertility
      indices were documented for 1449 dairy cows treated with dexamethasone
      trimethylacetate, with or without prostaglandin to induce calving. Equivalent
      data was collected for 603 untreated herd mates that calved at approximately the
      same time. RESULTS: The median interval from initial treatment to calving was 11
      days. Induction was associated with a substantially lower calf survival and
      commercial value of surviving calves. Calf viability and value was lower when
      induced cows were at an earlier stage of pregnancy. Retained foetal membranes,
      photosensitisation and other problems were significantly more frequent in the
      induced group compared to the untreated group. Milk production of induced cows
      was approximately 4% lower than untreated ones, but the majority of reproductive
      indices were not significantly different between the two groups. CONCLUSIONS: The
      practice of induction of parturition in seasonal calving dairy herds is a
      reliable way of shortening the gestation period of cows. Costs associated with
      morbidity and mortality of induced cows and losses in lactation and calf
      production are offset by benefits of improved reproductive performance and more
      efficient management of the herd. The welfare aspects of induction on calf
      survival must be considered.

PMID- 16958628
TI  - Dog health program in Numbulwar, a remote aboriginal community in east Arnhem
      Land.

PMID- 16958629
TI  - Detection of Anaplasma platys and Babesia canis vogeli and their impact on
      platelet numbers in free-roaming dogs associated with remote Aboriginal
      communities in Australia.
AB  - OBJECTIVE: To detect Anaplasma platys and Babesia canis vogeli infection, using
      polymerase chain reaction (PCR)-based assays, in free-roaming dogs associated
      with eight Aboriginal communities in remote areas of Australia and to determine
      the impact of infection through the assessment of platelet numbers. PROCEDURES:
      Blood samples from 215 dogs were screened by PCR for A platys and B canis vogeli
      using established genus-specific DNA primers for the 16S and 18S rRNA genes
      respectively. Both A platys DNA and B canis vogeli DNA were confirmed from the
      screening PCR either by sequencing or by the use of species-specific primers.
      Peripheral blood films from 92 of the 215 dogs were used to estimate platelet
      numbers through an indirect method. RESULTS: Of 215 dogs, 69 (32%) were positive
      for A platys, 22 (10%) for B canis vogeli and 24 (11%) for both. The two
      organisms were detected singularly and as coinfection in all communities. For the
      92 dogs in which peripheral blood films were examined, the mean estimated
      platelet counts for the non-infected dogs was 318 x 10(9)/L, those infected with
      A platys alone was 256 x 10(9)/L, those with B canis vogeli alone was 276 x
      10(9)/L and those infected with both parasites was 169 x 10(9)/L. In young dogs,
      infection produced significantly decreased mean platelet counts when compared to
      uninfected dogs. Thrombocytopenia (< 200 x 10(9)/L) was detected in 18 (51%) dogs
      infected with A platys alone, 3 (33%) dogs infected with B canis vogeli alone, 13
      (72%) dogs coinfected, and 8 (27%) uninfected dogs. CONCLUSIONS: A platys and B
      canis vogeli infection, either singularly or together, was widespread in free
      roaming dogs associated with remote Aboriginal communities in the Northern
      Territory and north-western New South Wales. Moreover, both A platys and B canis
      vogeli infections were associated with a reduction in mean platelet numbers in
      dog populations, particularly in young dogs. The fact that 51% of dogs infected
      with A platys alone and 72% dogs coinfected were thrombocytopenic compared to 27%
      of uninfected dogs suggests that the organism alone or in combination with B
      canis vogeli has the potential to cause thrombocytopenia and perhaps contribute
      to a clinical bleeding disorder in infected dogs.

PMID- 16958630
TI  - Tachycardia-induced cardiomyopathy in a young Boxer dog with supraventricular
      tachycardia due to an accessory pathway.
AB  - A 1-year-old male Boxer dog presented with sustained supraventricular tachycardia
      and tachycardia-induced cardiomyopathy. Conversion to sinus rhythm was achieved
      initially with intravenous lignocaine and subsequently with oral procainamide.
      Oral procainamide treatment was relatively successful in maintaining normal sinus
      rhythm with no side effects apart from a reversible change in coat colour.
      Electrophysiological studies demonstrated the presence of an accessory pathway
      connecting the right atrium to the right ventricle and confirmed the diagnosis of
      orthodromic atrioventricular reciprocating tachycardia. Radiofrequency catheter
      ablation of the accessory pathway led to permanent resolution of the
      supraventricular tachycardia and for 9.5 years the dog has had no further signs
      of cardiac disease. The successful treatment of this condition highlights the
      importance of differentiating tachycardia-induced cardiomyopathy from dilated
      cardiomyopathy.

PMID- 16958632
TI  - MRI findings of haematomyelia in a dog with spontaneous systemic haemorrhage.
AB  - A 7-year-old female cross-breed dog was brought to Nihon University Animal
      Medical Center for investigation of tetraplegia. Lameness in the pelvic limbs,
      that had developed 2 weeks previously, had progressed to tetraplegia. On magnetic
      resonance imaging of the spinal cord, isointensity was detected from C2 to C4 and
      T12 to T13, isointensity and hyperintensity were intermingled from L3 to L4, and
      hyperintensity was detected from L5 to L7 by T1-weighted imaging. On T2-weighted
      imaging, hyperintensity was detected in all regions described above. The dog
      recovered from anaesthesia, but died during the day from systemic bleeding as the
      result of a coagulopathy of unknown aetiology. Histopathological examination
      revealed haematomyelia in these regions of the spinal cord. This is the first
      report of magnetic resonance imaging findings of haematomyelia in canine
      spontaneous systemic haemorrhage. It appeared that the differences in the
      findings of T1-weighted imaging along the spinal regions reflected time-lags in
      the occurrence of bleeding.

PMID- 16958634
TI  - Serum and plasma cardiac troponin I concentrations in clinically normal
      Thoroughbreds in training in Australia.
AB  - Cardiac troponin I is a potentially useful test to identify cardiac muscle damage
      in the horse. Measurements of cardiac troponin I from serum or heparinised plasma
      samples from 23 clinically normal Thoroughbred horses in race training were
      analysed through a standard Australian commercial laboratory using the ADVIA
      Centaur Assay. The cardiac troponin I concentrations were < 0.15 microg/L from
      all samples. The test was then validated using macerated equine myocardium.
      Cardiac troponin I concentration may be useful in determining whether poor
      performance in Thoroughbred horses is related to active myocardial disease.

PMID- 16958636
TI  - Complementary, alternative, proven, unproven.

PMID- 16958637
TI  - Etanercept in severe active rheumatoid arthritis: first Australian experience.
AB  - BACKGROUND: Etanercept reduces disease activity in adults with chronic rheumatoid
      arthritis (RA) who are resistant to other therapies. Medicare Australia
      Pharmaceutical Benefit Scheme subsidized treatment (since August 2003) restricts
      etanercept availability to a most drug-resistant RA population. The aim of the
      study was to assess the efficacy of etanercept in this unique group after 12
      months of therapy. METHODS: A prospective study of the first 50 consecutive
      private practice, adult RA patients whom were commenced on etanercept. The
      primary efficacy measures included short form 36 scores, Disease Activity Score
      28, American College of Rheumatology (ACR) response improvement in per cent and
      the ACR individual core set components at baseline, 3 and 12 months. Analysis was
      by intention to treat. RESULTS: There was significant improvement in all mean
      short form 36 component scores (P < 0.05) and all ACR core set component scores
      (P < 0.05) comparing 12 months to baseline. The disease activity score 28 also
      significantly fell from baseline at both 3 and 12 months (P < 0.05). The ACR 20%
      response significantly improved (P < 0.05) both at baseline to 3 months 92%
      (81.2, 96.9) and to 12 months 80% (67.0, 88.8). Serious adverse events occurred
      in 16%. At 12 months 88% completed treatment. CONCLUSION: Etanercept therapy
      will, by 3 and 12 months, significantly improve the short form 36, disease
      activity score 28, ACR 20% response and core set components. Our results are
      similar to international studies using etanercept in efficacy and tolerance
      despite our cohort being more resistant to preceding drug therapy. Etanercept
      offers this unique active severe refractory late RA Australian population a new
      therapeutic option to control their disease.

PMID- 16958639
TI  - Strongyloides stercoralis: risks posed to immigrant patients in an Australian
      tertiary referral centre.
AB  - BACKGROUND: Strongyloides stercoralis is a nematode human parasite with a global
      prevalence that is able to maintain a prolonged infestation by means of its
      autoinfective life cycle. Immunosuppression may result in a life-threatening
      hyperinfection syndrome. Recent changes in migration have resulted in the arrival
      of many immigrants from endemic areas. As to whether physicians are alert to the
      risks of strongyloidiasis in these patient groups is unclear. The aim of the
      study was to assess the risks posed by chronic strongyloidiasis in patients
      presenting to a tertiary referral centre and the need for screening of immigrant
      patients before immunosuppression. METHODS: The study comprised a retrospective
      review of cases of strongyloidiasis presenting to the Alfred Hospital, Melbourne.
      Thirty-three cases were diagnosed by either positive serology or faecal
      microscopy between January 1998 and January 2005. The medical records for 29
      cases were examined with regard to demographics, clinical features and
      complications. RESULTS: Two major groups were identified: immigrants (17) and
      returned travellers (11). Six immigrants, but no returned traveller, developed a
      hyperinfective syndrome. Five immigrants received immunosuppressive therapies
      before developing symptoms of hyperinfection and this was complicated by life
      threatening sepsis in two patients. Diagnosis was frequently delayed in the
      immigrant group who were significantly more likely to present with respiratory
      symptoms. Four immigrants and two returned travellers were treated with
      corticosteroids for symptoms that were probably related to larval migration.
      CONCLUSION: Before giving immunosuppressive therapies, patients with a history of
      potential exposure must be investigated for strongyloidiasis and consideration
      given to empirical treatment.

PMID- 16958640
TI  - Effects of care pathways on stroke care practices at regional hospitals.
AB  - BACKGROUND: Our previous work identified deficiencies in stroke care practices at
      regional hospitals in comparison to standards suggested by published stroke care
      guidelines. These deficiencies might be improved by the implementation of
      clinical pathways. The aim of this study was to assess changes in acute stroke
      care practices following the implementation of stroke care pathways at four
      regional Queensland hospitals. METHODS: The medical records of two cohorts of 120
      patients with a discharge diagnosis of stroke or transient ischaemic attack were
      retrospectively audited before and after implementation of stroke care pathways
      to identify differences in the use of acute interventions, investigations and
      secondary prevention strategies. RESULTS: Following pathway implementation there
      were clinically important, but not statistically significant, increases in the
      rates of swallow assessment, allied health assessment (significant for
      occupational therapy, P = 0.04) and use of deep vein thrombosis prevention
      strategies (also significant, P = 0.006). Fewer patients were discharged on no
      anti-thrombotic therapy (statistically significant in the subgroup of patients
      with atrial fibrillation, P = 0.02). Only 37% of the patients audited were
      actually enrolled on the pathway. Among this subgroup there were significant
      increases in the rates of swallow assessment (first 24 h, P = 0.01; any time
      during admission, P = 0.0001), allied health assessments (all P < 0.05),
      estimation of blood glucose level (P = 0.0015) and the use of deep vein
      thrombosis prevention strategies (P = 0.0003). CONCLUSION: Stroke care pathways
      appear to improve the process of care. Whether this influences outcomes such as
      mortality, functional and neurological recovery, the incidence of complications,
      length of stay or the cost of care was beyond the scope of this study and will
      require further examination.

PMID- 16958641
TI  - Patients with acute myocardial infarction have an inaccurate understanding of
      their risk of a future cardiac event.
AB  - BACKGROUND: Accurate perceptions of future cardiac risk are important to ensure
      informed treatment choices and lifestyle adaptation in patients following
      myocardial infarction (MI). The aim of this study was to investigate whether risk
      perceptions of patients with MI were accurate compared with an established
      clinical risk model. METHODS: Seventy-nine consecutive patients with acute MI
      admitted to the Coronary Care Unit, Auckland Hospital, completed a questionnaire
      assessing risk perceptions. Clinical data were used to calculate patients'
      Thrombolysis In Myocardial Infarction (TIMI) risk scores, a validated predictive
      model of prognosis. The main outcome measures were the associations between
      perceived risk, TIMI risk scores and troponin T. RESULTS: Patients' risk
      perceptions showed no correlation with thrombolysis in myocardial infarction risk
      scores (r = -0.06; P = 0.61) or with troponin T (r = -0.07; P = 0.53). Patients'
      risk perceptions were not significantly associated with age or sex, and were not
      significantly higher in those who had experienced a previous MI, a family history
      of coronary heart disease, diabetes or smokers. Higher perceived risk was
      significantly associated with a number of illness perceptions, including worse
      consequences of the MI and lower beliefs in the benefit of treatment. Patients
      who overestimated their risk were more anxious than other patients (F(2, 73) =
      22.97; P = 0.0001). CONCLUSION: Patients with MI ideas about their personal risk
      of future MI are not congruent with their clinical risk assessments. Inpatient
      hospital care appears to be unsuccessful in communicating prognosis effectively
      to patients. Improving the accuracy of risk perceptions may help decrease
      unnecessary cardiac anxiety and invalidism in some patients and prompt risk
      reducing behaviours in others.

PMID- 16958642
TI  - Metabolic syndrome in older people in Taiwan: a hospital-based study.
AB  - BACKGROUND: The aim of this study was to investigate the prevalence of metabolic
      syndrome in older people in Taiwan. METHODS: This was a hospital-based, cross
      sectional study. We retrospectively analysed subjects receiving self-referred
      health examination at one medical centre in Taiwan from 2000 to 2004. In all, 696
      older people without any acute illness were enrolled in this study, 352 men
      (50.6%) and 344 women (49.4%). The mean age was 70.2 +/- 4.6 years (age range 65
      87). Metabolic syndrome was estimated according to the criteria proposed by
      National Cholesterol Education Program Adult Treatment Panel III in 2001 and by
      International Diabetes Foundation in 2005, with the cut-off values of the waist
      circumference greater than or equal to either 90 or 80 cm for men or women,
      respectively. RESULTS: Among this group, 94% of the individuals presented with at
      least one condition of metabolic syndrome. The prevalence of metabolic syndrome
      defined by National Cholesterol Education Program Adult Treatment Panel III was
      44.1% and was higher in women than in men (52.6 vs 35.8%, P < 0.001). Defined by
      International Diabetes Foundation, the prevalence was also 44.1% and was higher
      in women than in men (55.5 vs 33.0%, P < 0.001). CONCLUSION: The prevalence of
      metabolic syndrome remains relatively high in Taiwanese older people.

PMID- 16958643
TI  - Tauopathies: classification and clinical update on neurodegenerative diseases
      associated with microtubule-associated protein tau.
AB  - The majority of neurodegenerative diseases are characterized by the deposition of
      insoluble protein in cells of the neuromuscular system. Advances in molecular
      neuropathology have allowed a classification system of neurodegenerative diseases
      based on this protein accumulation. Microtubule-associated tau is one protein
      that has important functions in healthy neurons, but forms insoluble deposits in
      diseases now known collectively as tauopathies. Tauopathies encompass more than
      20 clinicopathological entities, including Alzheimer's disease, the most common
      tauopathy, progressive supranuclear palsy, Pick's disease, corticobasal
      degeneration and post-encephalitic parkinsonism. There are important clinical,
      pathological, biochemical and genetic similarities in the range of these diseases
      and they have helped to advance our understanding of the aetiological factors
      that initiate neurodegeneration and tau accumulation. This review examines the
      important clinical features of the most prevalent tauopathies and the molecular
      and pathological features that underpin the classification system.

PMID- 16958644
TI  - Continuing professional development for rural physicians: an oxymoron or just non
      existent?
AB  - There is geographic maldistribution of physicians across Australia and their
      professional isolation, particularly in relation to continuing professional
      development, is a definite problem. It tends to be worse in smaller centres where
      there is no critical mass that allows for peer support. Although some academic
      research has been carried out concerning the needs of rural GP, none has
      targetted rural specialists. Several activities, including the Commonwealth
      funded Support Scheme for Rural Specialists, have been well received and other
      initiatives, including the rural clinical schools and university departments of
      rural health, are beginning to provide an infrastructure that will help overcome
      the professional isolation through the use of innovative technologies such as
      interactive videoconferencing. This is being used to deliver RACP initiatives
      such as the basic physician trainee lecture series and the potential for vertical
      integration of training in rural settings which offer some promise to address the
      rural workforce shortage in the years to come.

PMID- 16958645
TI  - 'Right' way to 'do' illness? Thinking critically about positive thinking.
AB  - Exhortations to 'be positive' accompany many situations in life, either as a
      general injunction or in difficult situations where people are facing pressure or
      adversity. It is particularly evident in health care, where positive thinking has
      become an aspect of the way people are expected to 'do' illness in developed
      society. Positive thinking is framed both as a moral injunction and as a central
      belief system. It is thought to help patients cope emotionally with illness and
      to provide a biological benefit. Yet, the meanings, expectations and outcomes of
      positive thinking are infrequently questioned and the risks of positive thinking
      are rarely examined. We outline some of the latter and suggest that health
      professionals should exercise caution in both 'prescribing' positive thinking and
      in responding to patients and carers whose belief systems and feelings of
      obligation rest on it.

PMID- 16958646
TI  - Myeloid sarcoma of the uterus presenting as vaginal bleeding.
AB  - Extramedullary relapse of acute myeloid leukaemia may occur in sites such as the
      central nervous system, testes, and skin. Presentations in the female genital
      tract are uncommon and usually asymptomatic. In contrast, symptomatic uterine
      myeloid sarcoma is very rare. Treatment of this is generally unsuccessful, but is
      improved when systemic therapies are used. We study a case of a uterine relapse
      of acute myeloid leukaemia presenting as vaginal bleeding and successfully
      managed by local irradiation. The mechanism of preferential infiltration of
      uterine tissue requires further study.

PMID- 16958647
TI  - Safety of iron polymaltose given as a total dose iron infusion.
AB  - An audit of the in-hospital safety and tolerability of 401 infusions of iron
      polymaltose in 386 patients has shown no cases of anaphylaxis or other
      cardiorespiratory compromise. The infusion was terminated prematurely because of
      adverse events in six patients (1.6%). No adverse events occurred within the
      first 15 min of the infusion. Premedication (in 24%) was not associated with
      fewer adverse events. Fear of anaphylaxis should not inhibit the use of total
      dose iron infusion and the practices of premedication and of medical supervision
      during the first 15 min of the infusion should be abandoned.

PMID- 16958648
TI  - Disseminated tuberculosis.

PMID- 16958649
TI  - Pseudo-rheumatoid deformity in a patient with cerebrovascular disease.

PMID- 16958650
TI  - Lead nephropathy: early leads from descriptive studies.
AB  - Chronic lead exposure is recognized as a potential cause of hyperuricaemia,
      kidney damage and hypertension. The fascinating story of lead poisoning and
      nephrotoxicity illustrates the utility of descriptive studies in the early
      elucidation of a new disease entity. The pursuit towards understanding lead
      nephropathy is presented as a successful illustration of human occupational and
      public health.

PMID- 16958651
TI  - Rapid reversal of the chylomicronaemia syndrome with conservative management.

PMID- 16958652
TI  - Case of chlorambucil-induced seizure.

PMID- 16958653
TI  - Simple method for inflating and measuring oesophageal balloon pressure of
      Sengstaken-Blakemore tube.

PMID- 16958654
TI  - Lowering body iron stores in the prevention of type 2 diabetes.

PMID- 16958655
TI  - On being both professional and human.

PMID- 16958656
TI  - Proceedings of the International Symposium on Alcoholic Liver and Pancreatic
      Diseases and Cirrhosis, 18-19 May 2006, Marina del Rey, California, USA.

PMID- 16958657
TI  - Cell death in pancreatitis: effects of alcohol.
AB  - Pancreatitis is a severe and frequently lethal disorder, a major cause of which
      is alcohol abuse. Parenchymal cell death is a major complication of pancreatitis.
      In experimental models of (non-alcoholic) acute pancreatitis, acinar cells have
      been shown to die through both necrosis and apoptosis, the two principal pathways
      of cell death. The severity of experimental acute pancreatitis correlates
      directly with the extent of necrosis and inversely with apoptosis. Thus,
      understanding the regulation of apoptosis and necrosis, and whether it is
      possible to manipulate the pattern of death responses, is becoming exceedingly
      important in investigations of the pathogenesis and treatment of pancreatitis.
      The effects of alcohol on cell death responses of pancreatitis, and the
      mechanisms that may mediate these effects, are just starting to be explored. This
      paper reviews the signaling pathways mediating the balance between apoptosis and
      necrosis in acute pancreatitis, and alcohol's effects on cell death responses in
      pancreatitis.

PMID- 16958658
TI  - Anti-adipogenic regulation underlies hepatic stellate cell transdifferentiation.
AB  - Cirrhosis is the most important consequence of alcoholic liver disease for which
      liver transplantation is the only treatment option available.
      Transdifferentiation of hepatic stellate cells (HSC) to myofibroblastic cells
      (MF) is a central event in liver fibrogenesis, and understanding molecular
      mechanisms that underlie this cellular event provides pivotal insights into
      development of new therapeutic modalities for cirrhosis. To this end, the authors
      proposed several years ago that transdifferentiation of quiescent HSC to MF may
      be causally associated with transcriptional regulation known for adipocyte
      preadipocytic fibroblast dedifferentiation. In support of this notion, the
      authors showed that adipogenic transcription factors and their downstream
      adipocyte specific genes are expressed abundantly in quiescent HSC and that this
      expression profile is lost in HM. Further, gain-of-function manipulations for
      adipogenic transcription factors such as peroxisome proliferator-activated
      receptor-gamma (PPAR-gamma) and sterol regulatory element binding protein-1c have
      been shown to reverse culture-induced MF to quiescent HSC. The authors also
      demonstrated that tumor necrosis factor-alpha and Wnt, known mediators of anti
      adipogenesis, also suppress the activity of PPAR-gamma and contribute to HSC-MF
      transdifferentiation. These results reinforce the concept of adipogenic
      regulation essential to the quiescent phenotype and the loss of such regulation
      underlying HSC-HM transdifferentiation. They also provide insights into the
      molecular basis for the use of PPAR-gamma agonists, which has been advocated for
      treatment of liver fibrosis.

PMID- 16958660
TI  - International collaboration on alcoholic liver disease and pancreatitis:
      opportunities.

PMID- 16958659
TI  - The China Seven Cities Study and the Pacific Rim Transdisciplinary Tobacco and
      Alcohol Use Research Center.

PMID- 16958661
TI  - Action plan for enhancing global collaboration on alcoholic liver and pancreatic
      diseases: white paper.

PMID- 16958662
TI  - Role of Ca2+ in pancreatic cell death induced by alcohol metabolites.
AB  - Whereas alcohol itself, even in high concentrations, has little effect on the
      functional performance of isolated pancreatic acinar cells, non-oxidative
      metabolites (fatty acid ethyl esters [FAEE] and fatty acids [FA]) can cause
      Ca(2+)-dependent necrosis. The mechanism of action of FAEE has been investigated
      using a combination of patch clamp whole-cell current recording and Ca(2+)
      imaging. At low stimulation intensities, FAEE evoke repetitive short-lasting
      cytosolic Ca(2+) spikes, which are inhibited by caffeine, used as an inositol
      trisphosphate receptor antagonist. With more intense stimulation, sustained
      elevations of the cytosolic Ca(2+) concentration are observed, which can be
      prevented by pharmacological inhibition of the conversion of FAEE to FA. It is
      therefore the FA and not the FAEE that cause necrosis. The effect of FA cannot be
      blocked by inositol trisphosphate receptor antagonists. Fatty acids elicit a
      marked reduction in the cytosolic adenosine triphosphate (ATP) level. The patch
      clamp experiments show that the toxic sustained Ca(2+) signal generation induced
      by FA can be prevented by adding ATP to the cell interior. The toxic alcohol
      effects are principally due to FAEE produced under non-oxidative conditions and
      their subsequent conversion to FA. The FA-induced necrosis is Ca(2+)-dependent.
      The destructive sustained Ca(2+) signals are due to inhibition of mitochondrial
      function with failure of ATP generation.

PMID- 16958663
TI  - Vacuolar adenosine triphosphatase and pancreatic acinar cell function.
AB  - The pathologic activation of proteases within the pancreatic acinar cell is a key
      initiating event in acute pancreatitis. Past studies have suggested that the
      generation of a low-pH environment is critical to this process. Vacuolar
      adenosine triphosphatase (vATPase) is a multiprotein complex that transports
      protons across cellular membranes. Activation of the vATPase requires assembly of
      the soluble (V(1)) subunits on the membrane subunits (V(0)). It is found that
      conditions that cause protease activation in the acinar cell also cause assembly
      of V(1) on V(0). Further, inhibitors of vATPase block this protease activation.
      Ethanol and butanol sensitize the acinar cell to cholecystokinin-induced zymogen
      activation; vATPase inhibitors also blocked this activation. Activation of the
      vATPase may be central to the pathologic activation of proteases in the acinar
      cell and may also modulate the sensitizing effects of alcohols.

PMID- 16958664
TI  - Special remarks from the National Institute on Alcohol Abuse and Alcoholism.

PMID- 16958665
TI  - Cytochrome P450 2E1-dependent oxidant stress and upregulation of anti-oxidant
      defense in liver cells.
AB  - Induction of cytochrome P450 2E1 (CYP2E1) is a central pathway by which ethanol
      generates oxidative stress. Cytochrome P450 2E1 metabolizes many other
      toxicologic compounds. Toxicity of these agents is enhanced by ethanol, due to
      induction of CYP2E1. Cytochrome P450 2E1 is induced under a variety of
      physiological and pathophysiological conditions. The laboratory at Mount Sinai
      School of Medicine established HepG2 cell lines that constitutively express human
      CYP2E1. Ethanol, polyunsaturated fatty acids and iron were toxic to the HepG2
      cells that express CYP2E1 (E47 cells) but not control HepG2 cells. The E47 cells
      had higher glutathione levels than control HepG2 cells due to activation of the
      genes encoding the heavy and light subunits of gamma glutamyl cysteine synthetase
      (GCLC and GCLM). There was also a twofold increase in catalase, cytosolic and
      microsomal glutathione transferase, and heme oxygenase-1 (HO-1) in the E47 cells
      due to activation of their respective genes. These activations were prevented by
      anti-oxidants, suggesting that the upregulation of these anti-oxidant genes may
      reflect an adaptive mechanism to remove CYP2E1-derived oxidants. Increases in
      nuclear factor erythroid 2-related factor 2 (Nrf2) protein and mRNA were observed
      in livers of hepatocytes of chronic alcohol-fed and of pyrazole-treated rats or
      mice, conditions known to elevate CYP2E1. E47 cells showed increased Nrf2 mRNA
      and protein expression. Upregulation of GCLC and HO-1 in E47 cells is dependent
      on Nrf2. These results suggest that Nrf2 is activated and its levels are
      increased when CYP2E1 is elevated. It is suggested that Nrf2 plays a key role in
      the adaptive response against increased oxidative stress caused by CYP2E1.

PMID- 16958666
TI  - Alcohol-induced oxidative stress and cell responses.
AB  - Epidemiological and animal studies have demonstrated that alcohol abuse is
      directly associated with the increase of multiple organ diseases, such as liver
      injury, cardiovascular diseases, and neurological disorders. While the mechanisms
      of alcohol-induced cell injury and disease remain to be investigated, recent
      studies indicate that reactive oxygen species (ROS) may play an important role.
      Reactive oxygen species are able to cause various cellular injuries, such as DNA
      damage, lipid peroxidation and protein modification. Cellular systems are
      protected from ROS-induced cell injuries by an array of defenses composed of
      various anti-oxidants with different functions. When the ROS present in the
      cellular system overpower the defense systems, they will cause oxidative stress
      or cell injury, leading to the development of diseases. This article reviews
      recent literature on alcohol-induced ROS production, oxidative stress, signal
      transduction, and cellular responses. The implication of these processes in
      alcohol-related diseases is also discussed.

PMID- 16958667
TI  - Mitochondrial glutathione: hepatocellular survival-death switch.
AB  - Steatohepatitis represents an advanced stage of fatty liver disease that
      encompasses alcoholic (ASH) and non-alcoholic steatohepatitis (NASH). The
      progression from steatosis to steatohepatitis is poorly understood. One of the
      clues to this progression is the sensitization of hepatocytes to oxidative stress
      and cytokine-induced cell death. Mitochondrial glutathione (mGSH), which plays a
      central role in the control of mitochondrial reactive oxygen species (ROS)
      generation, modulates the sensitivity to cell death pathways. Mitochondrial GSH
      depletion due to alcohol-mediated alteration in mitochondrial membrane dynamics
      underlies the susceptibility of hepatocytes from alcohol-fed models to tumor
      necrosis factor (TNF), and in nutritional and genetic models of hepatic
      steatosis, mGSH depletion occurs due to the enrichment of mitochondria in free
      cholesterol, resulting in decreased mitochondrial membrane fluidity. The
      signaling of TNF through its membrane receptor TNFR1 from complex I to complex II
      is similar in hepatocytes depleted or not depleted in mGSH, yet hepatocellular
      susceptibility to TNF occurs if mGSH is depleted. Thus, mGSH is a critical factor
      in the development of steatohepatitis through sensitization of hepatocytes to
      inflammatory cytokines, and understanding the homeostasis of cholesterol and its
      trafficking to mitochondria may be of relevance in the pathophysiology of ASH and
      NASH.

PMID- 16958668
TI  - Regulation of Kupffer cell activity during chronic ethanol exposure: role of
      adiponectin.
AB  - There is a growing appreciation that adipose tissue is a multifunctional organ.
      In addition to its central role in lipid storage, adipose tissue secretes a
      diverse group of proteins, called adipokines, involved in lipid metabolism,
      insulin sensitivity, angiogenesis etc. Adipocytes also secrete various
      inflammatory and anti-inflammatory mediators. Adiponectin, an adipokine with
      potent anti-inflammatory properties, is thought to play an important role in the
      regulation of inflammation. The development of alcoholic liver disease is thought
      to involve increased pro-inflammatory activity, mediated in part by the
      activation of Kupffer cells. Chronic ethanol feeding sensitizes Kupffer cells to
      activation by lipopolysaccharide (LPS), leading to increased production of
      reactive oxygen species (ROS) and tumor necrosis factor-alpha (TNF-alpha). Recent
      studies have demonstrated a hepato-protective effect of adiponectin in the
      progression of alcoholic liver disease. Herein are summarized recent data
      demonstrating that adiponectin treatment can normalize LPS-stimulated ROS
      production and TNF-alpha expression in Kupffer cells after chronic ethanol
      feeding. These studies suggest that the hepato-protective activity of adiponectin
      is due, at least in part, to a direct anti-inflammatory effect of adiponectin on
      Kupffer cells.

PMID- 16958669
TI  - Causes and consequences of mitochondrial reactive oxygen species generation in
      hepatitis C.
AB  - Hepatitis C virus has developed mechanisms to alter the redox state of
      hepatocytes and this is associated with changes in mitochondrial structure and
      function. Chronic hepatitis C patients manifest hepatic oxidative stress and this
      is exacerbated by alcohol consumption and associated with fibrosis progression.
      Several viral proteins, including core and NS5a appear to contribute to reactive
      oxygen species (ROS) generation by mechanisms that involve both mitochondria and
      endoplasmic reticulum (ER). Hepatitis C virus (HCV) core protein localizes to
      both ER and mitochondria and has effects at both sites. At the mitochondria a
      chain of events is initiated by core binding, which consists of increased Ca(2+)
      uptake, increased mitochondrial superoxide production, oxidation of the
      mitochondrial glutathione pool, inhibition of electron transport complex I
      activity, and sensitization of mitochondria to Ca(2+)- and ROS-induced membrane
      permeability transition. These effects have been observed in isolated
      mitochondria, cells bearing full-length HCV replicons, and liver mitochondria
      derived from HCV transgenic mice. In addition to these direct effects on
      mitochondria, core protein has been shown to causes a state of ER stress and an
      increase in the efficiency of ER to mitochondria Ca(2+) transfer. The resulting
      oxidized redox state has a number of potential consequences for liver function.
      It interferes with the antiviral innate immune responses and potentiates fibrosis
      and carcinogenesis. Alcohol exacerbates these effects by increasing core-induced
      ROS production, further oxidizing the mitochondrial glutathione pool. The
      resulting mitochondrial effects may contribute to liver injury and oxidative
      stress seen in chronic hepatitis C.

PMID- 16958670
TI  - Interactions of cytokines, S-Adenosylmethionine, and S-Adenosylhomocysteine in
      alcohol-induced liver disease and immune suppression.
AB  - Alcoholic liver disease (ALD) remains a leading cause of death in the USA.
      Defining mechanisms for liver cell death in ALD in order to develop potential new
      agents for therapeutic intervention is a major focus of the authors' work.
      Abnormal cytokine metabolism is a major feature of ALD, and a thorough
      understanding of both mechanisms and interactions of cytokine overproduction and
      sensitization are critical to developing a possible treatment for ALD. S
      Adenosylmethionine has been used in a variety of animal studies and clinical
      trials and has been reported to improve biochemical parameters of liver function.
      Last, immunosuppression associated with chronic alcohol abuse is an important
      predisposing factor to opportunistic infections and cancer. It is the authors'
      working hypothesis that alcohol consumption leads to chronic activation of the
      immune system.

PMID- 16958671
TI  - Evaluation of the role of nuclear factor-kappaB signaling in liver injury using
      genetic animal models.
AB  - Most chronic liver diseases are not sufficiently treatable at present and very
      often progress to liver fibrosis and liver cirrhosis. Several recent studies have
      suggested that cytokines and cytokine-activated inflammatory signaling pathways
      might play an important role in the mediation of liver injury. Although pro
      inflammatory signaling pathways such as nuclear factor (NF)-kappaB have evolved
      primarily for host defense to infections, they appear to be involved in the
      pathogenesis of inflammatory diseases and may mediate liver injury in response to
      a variety of agents and pathogens. Herein is summarized briefly some recent
      findings concerning the role of NF-kappaB in different models of liver injury
      based on transgenic and knockout animal technology.

PMID- 16958672
TI  - SPINK1 gene mutations and pancreatitis in Japan.
AB  - SPINK1 can inhibit up to 20% of trypsin activity, and may constitute one major
      mechanism to protect the pancreas from autodigestion. In 2000, Witt et al. first
      recognized the association between mutations in the SPINK1 gene and chronic
      pancreatitis (CP), but the significance of SPINK1 gene mutation in pancreatitis
      and its relation to alcohol consumption remains unclear in Japan. The aim of the
      present paper was to clarify the incidence of SPINK1 mutations in CP patients
      with various etiologies in Japan and, in addition, to examine the relationship
      between alcohol metabolism and the polymorphisms in the key enzymes, alcohol
      dehydrogenase (ADH) and aldehyde dehydrogenase-2 (ALDH2). A total of 156 patients
      with CP, and 165 healthy volunteers, all Japanese, were examined for the SPINK1
      mutations by polymerase chain reaction-restriction fragment length polymorphism
      and direct sequencing. In Japan, the prevalence of [N34S; IVS1-37T > C] and [
      215G > A; IVS3 + 2T > C] was significantly higher in patients with idiopathic CP
      (10.6% and 12.8%, respectively) than normal subjects (0.6% and 0%). The frequency
      of the [-215G > A; IVS3 + 2T > C] mutation in Japan was significantly higher than
      that reported in other populations. Concerning alcoholic CP, the [-215G > A; IVS3
      + 2T > C] mutation was found in only a small number of patients (3.9%). On
      analysis of ADH2 and ALDH2 gene polymorphisms an association was found between
      ADH2*2 allele and alcoholic CP, and the ADH2*2/2*2 genotype had a tendency to
      increase the risk of developing pancreatic pseudocyst. In conclusion, in Japan
      the [-215G > A; IVS3 + 2T > C] mutation in the SPINK1 gene may form a unique
      genetic background for pancreatitis.

PMID- 16958673
TI  - Gene-environment factors that contribute to alcoholic pancreatitis in humans.
AB  - Alcohol-associated acute and chronic pancreatitis occur in a minority of alcohol
      users, suggesting that most drinkers are protected from pancreatic diseases while
      a subset is susceptible. Ongoing studies suggest that the pathophysiology is
      complex and can involve multiple genetic and environmental pathways and
      stochastic events. Both rat models and human genetic epidemiology studies have
      been used to understand susceptibility and modifying factors in humans. Rat
      studies suggest that different types of altered pancreatic physiology occur
      depending on dose, they occur rapidly and that alcohol changes the immune
      response to recurrent pancreatic injury. Human studies suggest that PRSS1 and
      SPINK1 mutation increase the pancreas' susceptibility to alcohol-associated
      pancreatitis, and that tobacco smoking, and some factors, affect disease
      progression.

PMID- 16958674
TI  - Alcohol and lipid metabolism.
AB  - Hepatic lipid metabolism is controlled by several master transcription factors,
      in particular peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and
      sterol response element binding protein-1 (SREBP-1). Peroxisome proliferator
      activated receptor-alpha is a receptor for free fatty acids (FFA), and can
      activate genes involved in transport, oxidation, and export of FFA. Sterol
      response element binding protein-1 is a sensor for the level of cholesterol in
      the liver, and is able to activate genes involved in synthesis of cholesterol and
      FFA. Chronic ethanol treatment of cells or animals inhibited PPAR-alpha function
      and activated SREBP. In addition, ethanol inhibited adenosine monophosphate
      dependent protein kinase (AMPK). The AMPK controls fatty acid metabolism by
      inhibiting acetyl-coenzyme A carboxylase, reducing malonyl-coenzyme A, and
      thereby permitting fatty acid transport into and oxidation in the mitochondrion.
      Adenosine monophosphate-dependent protein kinase was inhibited in alcohol-treated
      animals and cells. The mechanisms by which ethanol affects AMPK and the
      transcription factors are as yet incompletely understood.

PMID- 16958675
TI  - Methionine adenosyltransferase and S-adenosylmethionine in alcoholic liver
      disease.
AB  - Methionine adenosyltransferase (MAT) is an essential enzyme that catalyzes the
      formation of the principal methyl donor S-adenosylmethionine (SAMe). Studies in
      the past decade have shown that SAMe is not only a methyl donor, but also a key
      metabolite that regulates hepatocyte growth, death and differentiation.
      Abnormalities in MAT and decreased SAMe levels occur in experimental animals and
      humans with alcoholic liver disease. Chronic hepatic SAMe deficiency can result
      in the spontaneous development of steatohepatitis and hepatocellular carcinoma.
      This paper reviews MAT genes and SAMe in relation to alcoholic liver disease and
      the molecular mechanisms by which SAMe regulates hepatocyte growth and apoptosis.

PMID- 16958676
TI  - Role of matrix metalloproteinase-2 in ethanol-induced invasion by breast cancer
      cells.
AB  - Ethanol is a tumor promoter and may enhance the metastasis of breast cancer.
      However, the underlying cellular/molecular mechanisms remain unknown.
      Amplification of ErbB2, a receptor tyrosine kinase, is found in 20-30% of breast
      cancer patients. Ethanol preferably stimulates invasion by breast cancer cells
      over-expressing ErbB2 in vitro. Over-expression of ErbB2 is positively associated
      with elevated levels of matrix metalloproteinase-2 (MMP-2) and MMP-9. Ethanol at
      physiologically relevant concentrations activates MMP-2 without altering its
      expression level in mammary epithelial cells over-expressing ErbB2, but not in
      cells expressing low levels of ErbB2. The activation is dependent on c-jun N
      terminal kinases (JNK) and reactive oxygen species. Selective inhibitors of MMP-2
      and anti-oxidants significantly inhibit ethanol-stimulated cell invasion.
      Similarly, knocking down MMP-2 by small interference RNA induces a partial
      blockage on ethanol-promoted cell invasion. Matrix metalloproteinase-2 is
      predominantly expressed in stromal fibroblasts; ethanol also activates
      fibroblastic MMP-2. The conditioned medium collected from ethanol-exposed
      fibroblasts dramatically stimulates the invasion of breast cancer cells. The role
      of MMP-2 in ethanol-induced tumor promotion is discussed.

PMID- 16958677
TI  - Update on pancreatic cancer and alcohol-associated risk.
AB  - Ductal adenocarcinoma of the pancreas is characterized by extremely aggressive
      behavior, with an overall 5-year survival of <4%. Because conventional and
      specifically tailored therapeutic regimens have little impact on patient
      survival, epidemiological and molecular research aims at identifying and reducing
      risk factors. Cigarette smoking, obesity, diabetes mellitus, and chronic
      pancreatitis are amenable to medical prevention or therapy. Heavy alcohol
      consumption is an inconsistent single risk factor for pancreatic cancer but may
      promote carcinogenesis by increasing the risk of diabetes mellitus or chronic
      pancreatitis. For various agents, the key carcinogenic effect is probably an
      inflammatory response in the pancreatic tissue. On the molecular level, mutations
      of oncogenes and tumor suppressor genes, as well as various epigenetic
      alterations, such as overexpression of growth factors and their receptors, are
      important in tumorigenesis. Complete and safe surgical resection, together with
      adjuvant therapy, offers prolonged survival, with 5-year survival rates of
      approximately 25%. However, for unresectable or disseminated disease, which
      constitutes the vast majority of cases, treatment is palliative. Despite
      increasing knowledge about the molecular pathology of pancreatic cancer and
      despite advances in treatment, the overall course of the disease is dismal, and
      reinforced efforts to reduce incidence and improve outcome are needed
      desperately.

PMID- 16958678
TI  - Unfolding new mechanisms of alcoholic liver disease in the endoplasmic reticulum.
AB  - Intragastric ethanol feeding in mice induces expression of unfolded protein
      response/endoplasmic reticulum (UPR/ER) stress response genes. The proximate
      cause appears to be hyperhomocysteinemia, a well-known cause of ER stress in
      other contexts. Hyperhomocysteinemia appears to be due to downregulation of
      methionine synthase. The importance of homocysteine and ER stress in the
      pathogenesis of liver disease was suggested by the prevention of the alcohol
      induced changes by feeding sufficient betaine to lower homocysteine via betaine
      homocysteine methyl transferase. The ER stress, via CHOP, causes apoptosis and
      CHOP null mice exhibit no apoptosis. Alcohol-induced ER stress can activate
      sterol regulatory element-binding protein (SREBP)-1c and SREBP-2, which
      contribute to the accumulation of triglyceride and cholesterol.
      Hyperhomocysteinemia, ER stress and pathological changes of alcohol were
      minimally affected by absence of tumor necrosis factor receptor 1 (TNFR1) and the
      effect of betaine was also independent of TNF signaling. At present ER stress as
      an important factor in the pathogenesis of alcoholic liver disease is an exciting
      new hypothesis and ongoing research will need to further clarify its
      contribution. Among the issues in need of further elucidation are the role of ER
      stress induced by alcohol in SREBP regulation and fatty liver, as well as the
      precise mechanism of protection by betaine: decreased homocysteine, decreased S
      adenosylhomocysteine, or increased S-adenosylmethionine.

PMID- 16958679
TI  - In vivo imaging of hepatic fatty acid metabolism in patients with non-alcoholic
      steatohepatitis using semiquantitative 123I-labeled branched-chain fatty acid
      analog.
AB  - Obesity is now prevailing worldwide, coincident with the increase of hepatic
      steatosis. Metabolic syndrome with obesity and hypertension, hyperlipidemia, and
      impaired glucose tolerance is one of the most frequent life-threatening diseases
      and non-alcoholic steatohepatitis is believed to be a hepatic expression of this
      syndrome. Non-alcoholic steatohepatitis is prevalent and well characterized in
      Caucasians, but little is known about non-alcoholic steatohepatitis in Asia
      Oceania. Obesity will be a serious social problem in Asia-Oceania in the next two
      decades and we need to prevent the increase of this syndrome. Therefore, it is
      extremely important to know about non-alcoholic steatohepatitis based on racial
      differences, because this syndrome is likely to be a multi-factorial syndrome
      resulting from different combinations of susceptibility genes superimposed on
      different environmental factors. Because hepatic steatosis is the first step in
      the development of not only metabolic syndrome but also non-alcoholic
      steatohepatitis, the genetic background of Japanese NASH patients was
      investigated and a measure to assess fatty acid beta-oxidation in the liver in
      vivo was developed.

PMID- 16958680
TI  - Transcriptional regulation of stellate cell activation.
AB  - The identification of activated hepatic stellate cells and related cell types as
      key fibrogenic effectors during liver injury has led to intense evaluation of
      transcriptional events underlying their behavior. While initial studies focused
      on characterizing interactions between transcription factors and regulatory
      regions within gene promoters, epigenetic mechanisms have emerged as major
      determinants of gene activation and repression, in particular histone acetylation
      and promoter methylation, as well as other complex conditional interactions that
      underlie global changes in gene expression. Three examples are provided that
      illustrate how stellate cell activation may be controlled by widely divergent
      regulatory pathways, including alternative splicing of a growth inhibitory
      transcription factor (Kruppel-like factor-6), epigenetic regulation of a factor
      regulating stellate cell survival (nuclear factor kappaB), and regulation of a
      transcription factor whose expression maintains stellate cell quiescence (LIM
      homeobox gene 2 [Lhx2]). These complex cascades illustrate how clarifying the
      finely tuned interdependent layers of transcriptional, translational, post
      translational and epigenetic gene regulation in stellate cells is raising new
      prospects for therapy of hepatic fibrosis.

PMID- 16958681
TI  - Hepatic stellate cells and the reversal of fibrosis.
AB  - Hepatic fibrosis is an outcome of many chronic liver diseases, such as viral and
      autoimmune hepatitis, and of alcohol consumption and biliary obstruction.
      Prolonged liver injury results in hepatocyte damage, which triggers activation of
      hepatic stellate cells (HSC) and recruitment of inflammatory cells into the
      liver. The HSC play a critical role in fibrogenesis. They produce collagen type I
      and secrete pro-fibrogenic cytokines and inhibitors of matrix-degrading enzymes
      (tissue inhibitor of matrix metalloproteinase), causing the production of
      extracellular matrix deposition over degradation. However, many clinical and
      experimental studies suggest that this process can be reversed, including the
      apoptosis of activated HSC. Thus, HSC represent an appealing target for
      antifibrotic therapy. This review will focus on some aspects of etiology and
      molecular pathogenesis of liver fibrosis and the reversal of fibrosis.

PMID- 16958682
TI  - Matrix metalloproteinases, the pros and cons, in liver fibrosis.
AB  - Residing in the space of Disse within loose extracellular matrix (ECM) resembling
      that in basement membranes, the hepatic stellate cells (HSC) remain in quiescence
      as vitamin A storage cells. In response to liver injury HSC undergo morphologic
      and functional trans-differentiation, converting from vitamin A-storing, star
      like cells into contractile myofibroblastic cells, a process called activation.
      Accompanying cellular activation, the ECM components in the space of Disse switch
      from matrices rich in type-IV collagen and laminin, into condensed interstitial
      ECM, indicating that proteolytic degradation may occur to change the
      microenvironment in sinusoids as well as the fate of HSC. Indeed, matrix
      metalloproteinases (MMP), a family of ECM degradative enzymes, are promptly
      expressed by HSC in response to diverse hepatic toxins. In vitro experiments also
      demonstrated the role of MMP in activation of HSC cultured in 3-D ECM.
      Conversely, MMP may also contribute to regression of liver fibrosis through
      cleavage of the fibrillar ECM and promotion of apoptosis among the activated HSC.
      Thus, MMP play dual roles both bad and good in liver fibrosis, depending on the
      timing.

PMID- 16958683
TI  - Role of stellate cells in pancreatic fibrogenesis associated with acute and
      chronic pancreatitis.
AB  - Pancreas fibrosis is the result of a dynamic cascade of mechanisms beginning with
      acinar cell (AC) injury and necrosis and followed by inflammation, activation of
      macrophages, aggregation of platelets, release of growth factors and reactive
      oxygen species (ROS), activation of pancreatic stellate cells (PSC), stimulated
      synthesis of extracellular matrix and reduced matrix degradation. The result is a
      net matrix accumulation. Numerous in vivo and in vitro studies have provided
      strong evidence of a central role for PSC in fibrogenesis associated with acute
      and chronic pancreatitis. The PSC share homologies with hepatic stellate cells
      (HSC). In normal pancreas, the fat-storing phenotype of PSC is found in low
      numbers (approx. 4% of the cells) in the periacinar and interlobular space.
      Similar to the stellate cell-activating mechanisms in the liver, in pancreas
      injury PSC change their phenotype from the fat-storing to a highly active matrix
      producing cell type (activated PSC). The induction of the activated phenotype of
      PSC has been shown to involve a number of diverse extra- and intracellular
      effector molecules, including inflammatory cytokines, growth factors, ethanol,
      acetaldehyde, and oxidative stress.

PMID- 16958684
TI  - Battle-scarred pancreas: role of alcohol and pancreatic stellate cells in
      pancreatic fibrosis.
AB  - Pancreatic stellate cells (PSC) are now recognized as the key mediators of
      pancreatic fibrosis, a characteristic feature of chronic pancreatitis. The role
      of PSC in alcoholic pancreatic fibrosis has been examined in vivo (using
      pancreatic tissue from patients with alcohol-induced chronic pancreatitis and
      from animal models of experimental pancreatitis) and in vitro (using PSC in
      culture). These studies indicate that PSC are activated early in the course of
      pancreatic injury and are the predominant source of collagen in the fibrotic
      pancreas. The factors responsible for mediating PSC activation during chronic
      alcohol exposure include ethanol, its metabolite acetaldehyde, oxidant stress and
      cytokines (released during episodes of alcohol-induced pancreatic
      necroinflammation). Most recently, the intracellular signaling mechanisms
      regulating ethanol-induced PSC activation have been identified and include the
      mitogen-activated protein kinase (MAPK) pathway, phosphatidylinositol-3-kinase
      (PI3K) and protein kinase C (PKC), and the transcription factor activator protein
      1 (AP-1).

PMID- 16958685
TI  - Comparison between jaw bone augmentation by means of a stiff occlusive titanium
      membrane or an autologous hip graft: a retrospective clinical assessment.
AB  - OBJECTIVES: Patients in need of bone augmentation procedures can be treated with
      a traditional hip graft or by neogenesis under a stiff occlusive titanium
      membrane, custom-fit on the basis of CT-scan data. MATERIAL AND METHODS: Eighteen
      patients treated by means of a hip graft (H) were compared with 11 patients using
      a full titanium membrane (M) for the rehabilitation of upper jaws. In the H
      group, 17 patients (62 implants) in the anterior region (Ha) and 14 patients (23
      implants) in the posterior region (Hp) were included. In the M group, nine
      patients (30 implants) in the anterior region (Ma) and seven patients (16
      implants) in the posterior region (Mp) were included. RESULTS: In group Ha, the
      CFR was 13.3% after 14 years compared with group Ma where the CFR was 17.4% after
      9 years. In group Hp, the CFR was 22.8% after 16 years compared with group Mp
      where the CFR was 23.4% after 6 years. The marginal bone loss for group Ha after
      20 years was 2.7 mm, for group Ma it was not even 1 mm after 9 years; for group
      Hp, it was 2.5 mm after 15 years compared with less than 1 mm after 3 years in
      group Mp. CONCLUSIONS: The success rate of alveolar ridge augmentation therapy is
      lower than in a classical approach. These augmentation procedures, however, show
      acceptable results. The titanium membrane augmentation leads to less marginal
      bone loss probably because neo-formed bone has a better chance to adapt its
      mineralization to occlusal forces encountered. This technique could offer
      improvement if membrane exposure can be avoided.

PMID- 16958686
TI  - Effect of systemic administration of nicotine on healing in osseous defects. An
      experimental study in rabbits. Part II.
AB  - OBJECTIVES: The aim of the present study was to analyze the effect of systemic
      administration of nicotine on bone healing in osseous defects in the tibia of
      rabbits. MATERIAL AND METHODS: Sixteen female rabbits received nicotine (n=8;
      test group) or saline (n=8; control group) via subcutaneously placed mini-osmotic
      pumps for 8 weeks. The animals underwent three surgical operations during the
      experimental period, and body weight was registered weekly. Blood samples were
      collected to determine cotinine and prostaglandin E(2) levels. Bone preparations
      were made in the right leg of all rabbits after 4 weeks and in the left leg after
      6 weeks of nicotine/placebo exposure. Thus, 2- and 4-week healing groups were
      created for the bone defects. After 8 weeks, the animals were killed. Tissue
      blocks including the bone defects were prepared for histological analysis.
      RESULTS: The animals in the test group lost weight, while the control group
      gained weight during the experiment. The prostaglandin E(2) levels in plasma
      increased significantly following nicotine exposure in the test group. No
      significant differences in the percentage of vessels and bone density in the
      osseous defects were found between the test and the control groups after 2 and 4
      weeks of healing. CONCLUSIONS: In this experiment, systemic administration of
      nicotine over 4 or 6 weeks, respectively, influenced body weight and systemic
      prostaglandin E(2) levels but not the amount of blood vessels and the bone
      mineral density in bone defects after 2 or 4 weeks of healing.

PMID- 16958687
TI  - Bone associated with implants in diabetic and insulin-treated rats.
AB  - OBJECTIVES: Diabetes is an increasingly prevalent disease with oral health
      manifestations. While diabetes clearly has an affect on bone, its impact on the
      healing of bone associated with dental implants is not completely understood. The
      purpose of this study was to measure bone response to implants in uncontrolled
      and insulin-controlled diabetic rats. MATERIAL AND METHODS: One hundred and fifty
      two rats were divided into control, diabetic, and insulin groups. Rats received
      streptozotocin (65 mg/kg) to induce diabetes; animals in the insulin group also
      received a subcutaneous slow-release insulin implant. Titanium alloy implants
      (1.5 x 8 mm) were placed in the proximal tibiae of animals. Implants were
      harvested at 2, 7, 14, and 24 days and examined histologically. Bone or bone-like
      tissue adjacent to implants was quantified as a percent. Data were compared using
      a two-way analysis is variance (ANOVA) with time and treatment as primary
      independent factors. RESULTS: Time and treatment were significant factors in
      predicting bone response to implants (P<0.0001). Mean bone volume peaked at day 7
      and decreased over time to day 24. Mean bone volume percent at 2, 7, 14, and 24
      days (+/-SD) was 8.2 (+/-8), 22.9 (+/-8), 18.8 (+/-10), and 14.9 (+/-9),
      respectively. Mean total bone volume percent (adjusted for day) for control,
      diabetic, and insulin groups (+/-SD) was 12.4 (+/-9), 22.6 (+/-10), and 17 (+/
      7), respectively. Bone volume adjacent to implants in diabetic rats was
      significantly greater than controls (P<0.05). Diabetic animals treated with
      insulin were not statistically different from controls. CONCLUSIONS: Induction of
      diabetes with STZ is associated with increased bone response compared with
      controls. This response was mediated by treatment with insulin.

PMID- 16958688
TI  - Stability and marginal bone level measurements of unsplinted implants used for
      mandibular overdentures: a 1-year randomized prospective clinical study comparing
      early and conventional loading protocols.
AB  - OBJECTIVES: The aim of this study was to compare the performance of two non
      splinted implants used as retention for a mandibular overdenture when applying
      conventional or early loading protocols. MATERIAL AND METHODS: Twenty edentulous
      patients were treated with two unsplinted and non-submerged implants (15 mm long,
      TiUnite RP, Branemark System) in the anterior mandible. The patients were
      randomly allotted into two groups: (i) test group (Group A), in which the
      overdenture was connected 1 week after surgery, and (ii) control group (Group B),
      in which the overdenture was connected after 12 weeks of healing. Resonance
      frequency analyses (RFA) for implant stability measurements were performed at
      implant surgery and after 1, 3, 6, 9 and 12 months. Marginal bone levels were
      evaluated at implant surgery and after 6 and 12 months. RESULTS: No implant from
      either group was lost and all implants showed less than 1 mm of marginal bone
      resorption during the first year. The mean implant stability quotient (ISQ)
      values at implant surgery were 76.2+/-2.8 for Group A and 75.6+/-4.5 for Group B.
      The 12-month measurements showed 76.4+/-2.5 ISQ and 76.4+/-2.8 ISQ for Groups A
      and B, respectively. There were no statistically significant changes between or
      within the groups with time. There were no differences in marginal bone loss,
      which was on average 0.3 mm for both groups after 1 year. CONCLUSION: Although a
      limited number of patients were followed for 1 year only, the results of the
      present study indicate that early loading of two unsplinted 15 mm long implants
      with an overdenture does not negatively affect implant stability or marginal bone
      conditions when compared with implants subjected to 12 weeks of healing before
      loading.

PMID- 16958689
TI  - Survival and complication rates of combined tooth-implant-supported fixed partial
      dentures.
AB  - OBJECTIVES: The objective of this study has been to review the incidence of
      biological and technical complications in case of tooth-implant-supported fixed
      partial denture (FPD) treatments on the basis of survival data regarding clinical
      cases. MATERIAL AND METHODS: Based on the treatment documentations of a
      Bundeswehr dental clinic (Cologne-Wahn German Air Force Garrison), the medical
      charts of 83 patients with tooth-implant-supported FPDs were completely recorded.
      The median follow-up time was 4.73 (time range: 2.2-8.3) years. In the process,
      survival curves according to Kaplan and Meier were applied in addition to
      frequency counts. RESULTS: A total of 84 tooth-implant (83 patients) connected
      prostheses were followed (132 abutment teeth, 142 implant abutments (Branemark,
      Straumann). FPDs: the time-dependent illustration reveals that after 5 years, as
      many as 10% of the tooth-implant-supported FPDs already had to be subjected to a
      technical modification (renewal (n=2), reintegration (n=4), veneer fracture
      (n=5), fracture of frame (n=2)). In contrast to non-rigid connection of teeth and
      implants, technical modification measures were rarely required in case of tooth
      implant-supported FPDs with a rigid connection. There was no statistical
      difference between technical complications and the used implant system. Abutment
      teeth and implants: during the observation period, none of the functionally
      loaded implants (n=142) had to be removed. Three of the overall 132 abutment
      teeth were lost because of periodontal inflammation. The time-dependent
      illustration reveals, that after 5 years as many as 8% of the abutment teeth
      already required corresponding therapeutic measures (periodontal treatment (5%),
      filling therapy (2.5%), endodontic treatment (0.5%)). After as few as 3 years,
      the connection related complications of implant abutments (abutment or occlusal
      screw loosening, loss of cementation) already had to be corrected in
      approximately 8% of the cases. In the utilization period there was no screw or
      abutment fracture. CONCLUSION: Technical complications of implant-supported FPDs
      are dependent on the different bridge configurations. When using rigid functional
      connections, similarly favourable values will be achieved as in case of solely
      implant-supported FPDs. In this study other characteristics like different
      fixation systems (screwed vs. cemented) or various implant systems had no
      significant effect to the rate of technical complications.

PMID- 16958690
TI  - A five-year life-table analysis on wide neck ITI implants with prosthetic
      evaluation and radiographic analysis: results from a private practice.
AB  - This paper reports a 5-year life-table analysis on wide neck (WN) ITI implants
      placed in a private practice. In 212 patients, 263 implants were placed in the
      posterior region; 97% rehabilitated the molar area. Implants in the mandible and
      in the maxilla were 61.2% and 38.8%, respectively; the mean implant length was
      9.7 and 8.9 mm, respectively. Eighty-nine percent sites had both vestibular and
      buccal bone lamellae > or =1 mm, 9.1% had one of them <1 mm and 1.9% had both
      lamellae <1 mm. Sinus perforation during surgery occurred in 52% of the maxillary
      implants. Prosthetic information was available for 249 implants; implants were
      involved in 157 single crowns (SC) and 80 fixed partial dentures (FPD).
      Radiographic analysis was performed on 102 implants that reached the 2-year
      control, and crestal bone loss (CBL) was measured. Results showed that five
      implants failed; the 5-year cumulative survival rate was 97.89%. The 1-year
      survival rate based on 259 implants was 98.8% and the 2-year survival rate based
      on 174 implants was 97.7%. In this 5-year timeframe, 94.3% of the SCs and 96.2%
      of the FPDs were free of complication. The mean CBL at the mesial and distal
      sides was 0.71 and 0.60 mm, respectively; bone losses >1 and >2 mm were recorded
      for 29.7% and 2.5% of the sides, respectively. This mid-term study showed that
      the WN ITI implants were highly predictable in private practice and that
      prosthetic complication in the molar area was an infrequent event.

PMID- 16958691
TI  - Oxidized, bioactive implants are rapidly and strongly integrated in bone. Part 1-
      experimental implants.
AB  - OBJECTIVES: The study presented was designed to investigate the speed and the
      strength of osseointegration of oxidized implants at early healing times in
      comparison which machined, turned implants. MATERIAL AND METHODS: Screw-shaped
      titanium implants were prepared and divided into two groups: magnesium ion
      incorporated, oxidized implants (Mg implants, n=10) and machined, turned implants
      (controls, n=10). Mg implants were prepared using micro-arc oxidation methods.
      Surface oxide properties of implants such as surface chemistry, oxide thickness,
      morphology/pore characteristics, crystal structures and roughness were
      characterized with various surface analytic techniques. Implants were inserted
      into the tibiae of ten New Zealand white rabbits. After a follow-up period of 3
      and 6 weeks, removal torque (RTQ), osseointegration speed (DeltaRTQ/Deltahealing
      time) and integration strength of implants were measured. Bonding failure
      analysis of the bone-to-implant interface was performed. RESULTS: The speed the
      and strength of osseointegration of Mg implants were significantly more rapid and
      stronger than for turned implants at follow-up periods of 3 and 6 weeks. Bonding
      failure for Mg implants dominantly occurred within the bone tissue, whereas
      bonding failure for turned implants mainly occurred at the interface between
      implant and bone. CONCLUSIONS: Oxidized, bioactive implants are rapidly and
      strongly integrated in bone. The present results indicate that the rapid and
      strong integration of oxidized, bioactive Mg implants to bone may encompass
      immediate/early loading of clinical implants.

PMID- 16958692
TI  - Calprotectin and cross-linked N-terminal telopeptides in peri-implant and
      gingival crevicular fluid.
AB  - In a previous study on guided bone augmentation, a new collagen membrane was
      compared with an e-PTFE one on 28 partially edentulous patients who received 50
      dental implants at stage 2 surgery. After implant integration and subsequent
      loading, we were able to recruit 22 patients with 22 implants and their contra
      lateral corresponding teeth for longitudinal observation. Clinical parameters
      probing depth (PD), bleeding on probing (BoP), plaque index (PI), assessment of
      gingival crevicular fluid (GCF) and peri-implant crevicular fluid (PCF) volumes
      and periapical radiographs were performed at 2- and 3-year control appointments.
      Calprotectin (MRP 8/14) and cross-linked N-terminal telopeptide (NTx) levels in
      both crevicular fluids were determined by ELISA. PD was significantly reduced
      from years 2 to 3 appointments at implant sites as at teeth sites. At the 3-year
      appointment in both compartments, fluid volumes were significantly increased,
      which corresponded well with ascending NTx levels. The total amount of
      calprotectin decreased non-significantly in both GCF and PCF samples. Periapical
      radiographs revealed stable bone conditions around implants without significant
      changes from years 2 to 3 examinations. Clinical peri-implant parameters were
      considered as stable as the periodontal parameters of their corresponding teeth.
      A parallel increase in NTx levels in both GCF and PCF at 3-year appointment is
      not clearly understood; it may reflect an upregulation in the overall bone
      turnover rate.

PMID- 16958693
TI  - Characterization of human bone cells derived from the maxillary alveolar ridge.
AB  - In this study, we have characterized bone cell cultures derived from the human
      maxillary alveolar ridge, which could be a potential cell source for tissue
      engineering of the severely resorbed maxilla. From 10 individuals, an osseous
      core was obtained. Without the use of collagenase, 10 explant cultures were
      established and the morphology of the cells (human maxilla-derived cells (hMDCs))
      was studied with light microscopy (LM). Explant cultures were analyzed by flow
      cytometry with respect to size, granularity and surface marker expression.
      Fluorochrom-conjugated monoclonal antibodies (CD13, CD31, CD44, CD90 or CD73)
      were used. hMDCs were cultured in standard medium (SCM) or osteoinductive medium
      (OIM) for 21 days and analyzed for the presence of alkaline phosphatase (ALP) and
      calcium deposits (Von Kossa). Furthermore, osteogenic gene expression
      (osteocalcin [OC], ALP, collagen type 1) were analyzed by reverse transcription
      polymerase chain reaction (RT-PCR). LM demonstrated that hMDCs had a polygonal
      morphology containing a central nucleus with two to three nucleoli.
      Size/granularity analysis revealed differences between individuals.
      Immunophenotypically, these cells were positive for CD13, CD44, CD90 and CD73
      while negative for CD31. Cells cultured in SCM for 21 days showed moderate ALP
      staining and many calcium deposits. Culturing cells in OIM for 21 days
      significantly increased both ALP staining and the number of calcium deposits. RT
      PCR demonstrated expression of osteogenic marker genes and the ability to
      upregulate osteocalcin and ALP in response to osteogenic inducers. To our
      knowledge, it is the first time that surface marker expression has been studied
      on bone cells originating from this site. Cells were positive for markers
      characteristic for immature mesenchymal stem cells and had osteogenic
      differentiation capability. This study indicates that cells derived from
      maxillary biopsies could be a potential cell source for bone tissue engineering.

PMID- 16958694
TI  - Neural response to sandblasted/acid-etched, TiO-blasted, polished, and
      mechanochemically polished/nanostructured titanium implant surfaces.
AB  - The purpose of this study was to explore morphologic, functional, and behavioral
      effects of rough (sandblasted-large grid/acid-etched (SLA) and TiO2 blasted),
      mechanically polished, and mechanochemically polished titanium implant surfaces
      on nerves. The compound action potentials (cAPs) of sciatic nerves of sacrificed
      Wistar rats (n=10) were quantified at the in vitro level, while contacting disk
      shaped test specimens. The test specimens were also implanted directly on the
      sciatic nerves of another group of animals (n=33), hot-plate tests were
      undertaken for 10 consecutive days, and then the animals were sacrificed.
      Quantification of signal transduction speeds and cAPs of the nerves of these
      animals were undertaken at the in vitro level. Finally, the nerves were processed
      for histologic analysis. The signal transduction speeds and duration of cAPs of
      all groups were similar (P>0.05), whereas the amplitudes of cAPs of nerves
      contacting SLA implants were higher than those of TiO2 blasted and
      mechanochemically polished surfaces (P<0.05). Response latencies of nerves
      contacting mechanically polished specimens were slightly higher than the other
      groups (P>0.05). Histologic evaluations did not reveal any signs of adverse
      tissue response adjacent to specimens tested. Rough and polished titanium implant
      surfaces lead to similar neural response in vivo and in vitro that fall into
      physiologic limits.

PMID- 16958695
TI  - Bone response adjacent to calcium phosphate electrostatic spray deposition coated
      implants: an experimental study in goats.
AB  - BACKGROUND: A new technique to deposit calcium phosphate (CaP) coatings onto
      titanium substrates has been developed recently. This electrostatic spray
      deposition (ESD) technique seems to be very promising. It appears to have
      clinical advantages such as an inexpensive and simple set-up, high deposition
      efficiency and the possibility to synthesize layers with a defined surface
      morphology. OBJECTIVE: The aim of this study was to examine biological properties
      and osteoconductivity of ESD CaP coatings when inserted into the femoral condyle
      of a goat. MATERIAL AND METHODS: Twenty-four implants with two gaps, i.e. 1 or 2
      mm, were inserted into the femoral condyles of six goats. The implants were
      coated on one side with either a commercially available plasma-sprayed
      hydroxyapatite (HAPS) coating or an ESD carbonate apatite (CAESD) coating. The
      other side of the implant was always left uncoated (Ti). Twelve weeks after
      implantation the animals were sacrificed and the characteristics of bone ingrowth
      and bone contact were evaluated. RESULTS: At 3 months, histological and
      quantitative histomorphometrical measurements demonstrated more bone ingrowth and
      bone contact for coated sites as compared with uncoated sites. Statistical
      testing revealed that for both the 1 and 2 mm gaps HAPS (plasma-sprayed
      hydroxyapatite) as well as CAESD (ESD carbonate apatite) -coated surfaces always
      had a significantly higher (P<0.05) amount of bone contact than uncoated Ti
      surfaces. On HAPS surfaces always significantly more bone was present than on
      CAESD surfaces. Further statistical testing revealed a significant difference in
      bone ingrowth between the HAPS as well as CAESD and Ti 1+2 mm gap specimens
      (P<0.05). Further, HAPS 1 mm gaps showed more bone ingrowth than CAESD 1 mm gaps.
      No significant difference existed between HAPS and CAESD 2 mm gaps. CONCLUSION:
      On the basis of our observations, we conclude that the used ESD technique is a
      promising new method to deposit CaP coatings onto titanium substrates. On the
      other hand, plasma-spray HA-coated implants have a still more favourable effect
      on the bone response.

PMID- 16958696
TI  - Time- and dose-dependent mitogenic effect of basic fibroblast growth factor
      combined with different bone graft materials: an in vitro study.
AB  - OBJECTIVES: In periodontal regeneration, the growth factor concentrations and the
      delivery system used are of great importance. In an attempt to assess the
      mitogenic effect of basic fibroblast growth factor (bFGF) on periodontal ligament
      (PDL) cells combined with different bone replacement materials, two allografts of
      cortical (DFDBA) and cancellous (DFBA) bone and an anorganic bovine material with
      a synthetic peptide (ABM P-15) were used. The purpose of this study was to
      evaluate the in vitro mitogenic effect of different doses of bFGF alone or in
      combination with DFDBA, DFBA and ABM P-15 on human PDL cells in a time-dependent
      mode. MATERIAL AND METHODS: PDL cell cultures were derived from the mid-root of
      four maxillary premolars. Cells were grown and reached confluence. On day 2 of
      quiescence, new medium was added along with (1) 1, 5, 10 and 25 ng/ml of bFGF
      alone, (2) 10 mg of DFDBA, DFBA and ABM P-15 alone and (3) their combination. The
      mitogenic effect was determined at 24 and 48 h of culture by using a
      hemocytometer chamber. The cells were counted under a phase contrast microscope.
      RESULTS: The results revealed that bFGF at the highest concentrations and after
      48 h exerted a significant mitogenic effect on PDL cells, and also DFDBA and DFBA
      supported cell proliferation. Furthermore, DFDBA and DFBA enriched with bFGF had
      a significant mitogenic effect after 48 h of culture. ABM P-15 with 10 and 25
      ng/ml of bFGF up-regulated PDL cell proliferation after 48 h of incubation.
      CONCLUSIONS: The findings of this study demonstrate the beneficial role of bFGF
      combined with DFDBA and DFBA as carriers in periodontal repair.

PMID- 16958697
TI  - Comparison of hard tissue density changes around implants assessed in digitized
      conventional radiographs and subtraction images.
AB  - OBJECTIVES: The aim of this in vivo study was to compare peri-implant bone
      density assessed by the mean gray value of the histogram in digitized
      conventional radiographs and two digital subtraction images (DSI) methods: linear
      and logarithmic. MATERIAL AND METHODS: Thirty-four patients were monitored by
      standardized periapical radiographs 1 week after surgery and 4 months later. The
      radiographs were digitized and manipulated by means of EMAGO software. Linear and
      logarithmic DSI were obtained, and a filter was added to the logarithmic image.
      Control and test regions were selected and the mean value of the gray level of
      the histogram of these selected areas was obtained. This process was carried out
      in the digitized conventional radiographs (DCR) and the two methods of DSI. After
      that, the images were divided into two groups, with and without bone loss, and
      statistical analysis was performed. RESULTS: The results indicate that
      differences between the jaws did not reach significance, in all the images and in
      the two groups with and without bone loss. Furthermore, there was no
      statistically significant difference between the radiographic density assessed in
      the DCR and the two methods of subtraction images. CONCLUSIONS: Monitoring of
      peri-implant bone density by the mean gray value of the histogram in a selected
      area can be assessed either by linear and logarithmic DSI or by DCR.

PMID- 16958698
TI  - Zirconia-implant-supported all-ceramic crowns withstand long-term load: a pilot
      investigation.
AB  - OBJECTIVES: The purpose of this pilot investigation was to test whether zirconia
      implants restored with different all-ceramic crowns would fulfill the
      biomechanical requirements for clinical use. Therefore, all-ceramic Empress-1 and
      Procera crowns were cemented on zirconia implants and exposed to the artificial
      mouth. Afterwards, the fracture strength of the all-ceramic implant-crown systems
      was evaluated. Conventional titanium implants restored with porcelain-fused-to
      metal (PFM) crowns served as controls. MATERIAL AND METHODS: Sixteen titanium
      implants with 16 PFM crowns and 32 zirconia implants with 16 Empress-1 crowns and
      16 Procera crowns each--i.e., three implant-crown groups--were used in this
      investigation. The titanium implants were fabricated using the ReImplant system
      and the zirconia implants using the Celay system. The upper left central incisor
      served as a model for the fabrication of the implants and the crowns. Eight
      samples of each group were submitted to a long-term load test in the artificial
      mouth (1.2 million chewing cycles). Subsequently, a fracture strength test was
      performed with seven of the eight crowns. The remaining eight samples of each
      group were not submitted to the long-term load in the artificial mouth but were
      fracture-tested immediately. One loaded and one unloaded sample of each group
      were evaluated regarding the marginal fit of the crowns. RESULTS: All test
      samples survived the exposure to the artificial mouth. Three Empress-1 crowns
      showed cracks in the area of the loading steatite ball. The values for the
      fracture load in the titanium implant-PFM crown group without artificial loading
      ranged between 420 and 610 N (mean: 531.4 N), between 460 and 570 N (mean: 512.9
      N) in the Empress-1 crown group, and in the Procera crown group the values were
      between 475 and 700 N (mean: 575.7 N) when not loaded artificially. The results
      when the specimens were loaded artificially with 1.2 million cycles were as
      follows: the titanium implant-PFM crowns fractured between 440 and 950 N (mean:
      668.6 N), the Empress-1 crowns between 290 and 550 N (mean: 410.7 N), and the
      Procera crowns between 450 and 725 N (mean: 555.5 N). No statistically
      significant differences could be found among the groups without artificial load.
      The fracture values for the PFM and the Procera crowns after artificial loading
      were statistically significantly higher than that for the loaded Empress-1
      crowns. There was no significant difference between the PFM crown group and the
      Procera group. CONCLUSIONS: Within the limits of this pilot investigation, it
      seems that zirconia implants restored with the Procera crowns possibly fulfill
      the biomechanical requirements for anterior teeth. However, further
      investigations with larger sample sizes have to confirm these preliminary
      results. As three Empress-1 crowns showed crack development in the loading area
      of the steatite balls in the artificial mouth, their clinical use on zirconia
      implants has to be questioned.

PMID- 16958699
TI  - Releasing growth factors from activated human platelets after chitosan
      stimulation: a possible bio-material for platelet-rich plasma preparation.
AB  - INTRODUCTION: Thrombin is commonly used for activating the platelets and
      releasing the growth factors on the application of platelet-rich plasma (PRP). We
      have previously reported that chitosan can enhance rabbit platelet aggregation.
      In this study, the effects of chitosan on the subsequent growth factors release
      after human platelets activation were examined to evaluate the possibility of
      chitosan being used as a substitute for thrombin during PRP preparation. MATERIAL
      AND METHODS: Human platelet activation was determined by aggregation, adhesion
      and alpha-granule membrane glycoprotein expression. Platelet aggregation was
      measured by the turbidimetric method, the adhesion was directly examined on
      chitosan-coated glass plates under light microscope and scanning electron
      microscope (SEM), and the alpha-granule membrane glycoprotein was detected by
      fluorescent isothiocyanate (FITC)-conjugated anti-CD61 antibody through flow
      cytometry. The subsequent epidermal growth factor (EGF), platelet-derived growth
      factor (PDGF)-AB and transforming growth factor (TGF)-beta1 release from
      platelets were assayed by ELISA after mixing with chitosan. RESULTS: The
      enhancing effects on the platelet adhesion and the aggregation from chitosan were
      observed. Under both microscopes, the adhesive platelets on the chitosan-coated
      plates were not only greater in number but also earlier in activation than those
      on the control plates. With flow cytometry, increased glycoprotein IIIa
      expression in platelets was detected after chitosan treatment. Greater
      concentrations of growth factors were measured from PRP after chitosan treatment
      than after the solvent treatment. CONCLUSION: Because of the observations of
      growth factors releasing from activated human platelets after chitosan
      stimulation, we suggest that chitosan may be an appropriate substitute for
      thrombin in PRP preparation.

PMID- 16958700
TI  - Simultaneous implant placement and bone regeneration around dental implants using
      tissue-engineered bone with fibrin glue, mesenchymal stem cells and platelet-rich
      plasma.
AB  - This study was undertaken to evaluate the use of tissue-engineered bone as
      grafting material for alveolar augmentation with simultaneous implant placement.
      Twelve adult hybrid dogs were used in this study. One month after the extraction
      of teeth in the mandible region, bone defects on both sides of the mandible were
      induced using a trephine bar with a diameter of 10 mm. Dog mesenchymal stem cells
      (dMSCs) were obtained via iliac bone biopsy and cultured for 4 weeks before
      implantation. After installing the dental implants, the defects were
      simultaneously implanted with the following graft materials: (i) fibrin, (ii)
      dMSCs and fibrin (dMSCs/fibrin), (iii) dMSCs, platelet-rich plasma (PRP) and
      fibrin (dMSCs/PRP/fibrin) and (iv) control (defect only). The implants were
      assessed by histological and histomorphometric analysis, 2, 4 and 8 weeks after
      implantation. The implants exhibited varying degrees of bone-implant contact
      (BIC). The BIC was 17%, 19% and 29% (control), 20%, 22% and 25% (fibrin), 22%,
      32% and 42% (dMSCs/fibrin) and 25%, 49% and 53% (dMSCs/PRP/fibrin) after 2, 4 and
      8 weeks, respectively. This study suggests that tissue-engineered bone may be of
      sufficient quality for predictable enhancement of bone regeneration around dental
      implants when used simultaneous by with implant placement.

PMID- 16958701
TI  - A comprehensive and critical review of dental implant placement in diabetic
      animals and patients.
AB  - OBJECTIVES: A thorough and exhaustive analysis of the available studies
      concerning placement of endosseous dental implants in diabetic subjects has not
      been previously published. The aim of the present study was to perform a
      comprehensive and critical review of experimental and clinical studies published
      in the international peer-reviewed literature in the English language regarding
      endosseous implant installation in diabetic subjects and to draw evidence-based
      conclusions on the effectiveness and predictability of dental implant therapy in
      diabetic patients. MATERIAL AND METHODS: Literature search for articles published
      up to and including March 2005 in the English language was performed with a
      personal computer (PC) using The National Library Of Medicine
      (http://www.ncbi.nlm.nih.gov/PubMed) and Cochrane Oral Health Group databases.
      Search strategy included a specific series of terms and key words. The reference
      lists of identified publications, relevant texts and previous workshops were also
      scanned. Data sources also included several hand-searched journals and contact
      with experts, when it was considered appropriate. Search was conducted
      independently by the three reviewers (S. K., I. K. K., I. F.). At the first phase
      of selection the titles and abstracts and at the second phase full papers were
      screened independently by the three reviewers. Disagreement regarding inclusion
      of full papers was resolved by discussion among the reviewers. RESULTS: The
      search provided 227 potentially relevant titles and abstracts. At the first phase
      of evaluation, 199 publications were rejected based on title and abstract. At the
      second phase, the full text of the remaining 28 publications was retrieved for
      more detailed evaluation. These publications included 11 experimental studies and
      16 clinical studies (one clinical study corresponded to two publications).
      Finally, 11 experimental and eight clinical studies were accepted. Clinical
      studies included four prospective and four retrospective studies. Because of the
      limited number of available studies and their heterogeneity, focusing on a
      specific predefined question to be answered by a systematic review was not
      feasible and therefore no meta-analysis was planned. CONCLUSION: Within the
      limits of the existing investigations, experimental studies seem to reveal an
      impaired bone healing response to implant placement in diabetic animals compared
      with non-diabetic controls, both quantitatively and qualitatively. The majority
      of clinical studies tend to indicate that diabetes is no contraindication for
      implant placement, on condition that it remains under metabolic control. However,
      definitive guidelines with objective criteria, such as type and duration of
      diabetes and glucosylated hemoglobin levels, need to be established in the
      future.

PMID- 16958702
TI  - Spiritual but not religious? Evidence for two independent dispositions.
AB  - Some psychologists treat religious/spiritual beliefs as a unitary aspect of
      individual differences. But a distinction between mysticism and orthodox religion
      has been recognized by scholars as well as laypersons, and empirical studies of
      "ism" variables and of "spirituality" measures have yielded factors reflecting
      this distinction. Using a large sample of American adults, analyses demonstrate
      that subjective spirituality and tradition-oriented religiousness are empirically
      highly independent and have distinctly different correlates in the personality
      domain, suggesting that individuals with different dispositions tend toward
      different styles of religious/spiritual beliefs. These dimensions have low
      correlations with the lexical Big Five but high correlations with scales (e.g.,
      Absorption, Traditionalism) on some omnibus personality inventories, indicating
      their relevance for studies of personality.

PMID- 16958703
TI  - Basic personality dispositions, self-esteem, and personal goals: an approach
      avoidance analysis.
AB  - This research examined the hypothesis that self-esteem negatively predicts
      avoidance (relative to approach) personal goals, as well as the hypothesis that
      self-esteem mediates the link between indicators of approach and avoidance
      temperament and avoidance (relative to approach) personal goals. Study 1
      established that self-esteem is indeed negatively related to avoidance (relative
      to approach) goals, even with social desirability concerns controlled. In Study
      2, self-esteem was found to mediate the relation between Neuroticism
      (conceptualized as an indicator of avoidance temperament) and avoidance (relative
      to approach) personal goals. In Study 3, self-esteem was documented as a mediator
      of the relation between BAS and BIS sensitivity (conceptualized as indicators of
      approach and avoidance temperament, respectively) and avoidance (relative to
      approach) personal goals in the achievement domain. The implications of these
      findings for our understanding of basic personality dispositions, self-esteem,
      and personal goals are discussed.

PMID- 16958704
TI  - Putting the five-factor model into context: evidence linking big five traits to
      narrative identity.
AB  - The study examined relationships between the Big Five personality traits and
      thematic content extracted from self-reports of life history data. One hundred
      and five "mature age" university students (M=30.1 years) completed the NEO PI-R
      trait measure, and the Personality Web Protocol. The protocol examines
      constituents of identity by asking participants to describe 24 key "attachments"
      from their life histories (significant events, people, places, objects, and
      possessions). Participants sorted these attachments into clusters and provided a
      self-descriptive label for each cluster (e.g., "adventurous self"). It was
      predicted that the thematic content of these cluster labels would be
      systematically related to Big Five trait scores (e.g., that labels referring to
      strength or positive emotions would be linked to Extraversion). The hypothesized
      links were obtained for each of the Big Five trait domains except
      Conscientiousness. Results are discussed with a view to broadening our
      understanding of the Five-Factor Model in relation to units of personality other
      than traits.

PMID- 16958705
TI  - Is keeping a secret or being a secretive person linked to psychological symptoms?
AB  - This prospective study explored whether keeping a major secret, self-concealment
      (i.e., the predisposition to keep secrets), and social support at Time 1
      predicted symptomatology levels 9 weeks later (Time 2) among a sample of 86
      undergraduates. The results showed that the process of keeping a secret actually
      predicted fewer symptoms, whereas the personality variable of self-concealment
      predicted more symptoms at Time 2, even when the analyses controlled for social
      support. However, the predictive effects of both secret keeping and self
      concealment were wiped out when the analyses statistically controlled for initial
      symptomatology, which was positively linked to self-concealment from the outset.
      These findings challenge conventional wisdom about the dangers of keeping a major
      secret and suggest that, instead, the kind of person who is secretive simply
      might be more vulnerable to symptoms.

PMID- 16958706
TI  - Continuity and change in the life story: a longitudinal study of autobiographical
      memories in emerging adulthood.
AB  - If a person's internalized and evolving life story (narrative identity) is to be
      considered an integral feature of personality itself, then aspects of that story
      should manifest some continuity over time while also providing evidence regarding
      important personality change. Accordingly, college freshmen and seniors provided
      detailed written accounts of 10 key scenes in their life stories, and they
      repeated the same procedure 3 months and then 3 years later. The accounts were
      content analyzed for reliable narrative indices employed in previous studies of
      life stories: emotional tone, motivational themes (agency, communion, personal
      growth), and narrative complexity. The results showed substantial continuity over
      time for narrative complexity and positive (vs. negative) emotional tone and
      moderate but still significant continuity for themes of agency and growth. In
      addition, emerging adults (1) constructed more emotionally positive stories and
      showed (2) greater levels of emotional nuance and self-differentiation and (3)
      greater understanding of their own personal development in the 4th year of the
      study compared to the 1st year. The study is the first to demonstrate both
      temporal continuity and developmental change in narrative identity over time in a
      broad sampling of personally meaningful life-story scenes.

PMID- 16958707
TI  - Couple similarity and marital satisfaction: are similar spouses happier?
AB  - This study examined the role of couple similarity in spouses' marital
      satisfaction and affect. The associations between spousal similarity and
      relationship measures were examined in a sample of 248 married couples. As
      hypothesized, greater similarity between partners was associated with higher
      levels of marital satisfaction and lower levels of negative affect. In
      particular, similarity on the gendered personality and values domains was more
      strongly associated with relationship measures, whereas similarity on the
      attitudes and religiosity domains showed weaker and inconsistent patterns of
      associations. Finally, profile-based similarity tended to be a stronger and more
      consistent correlate of relationship measures than difference score-based
      similarity. The implications of these findings for processes underlying intimate
      relationships are discussed.

PMID- 16958708
TI  - The dynamic process of life satisfaction.
AB  - Drawing from the Cognitive Affective Personality System (Mischel & Shoda, 1995,
      1998), we argue for a need to examine within-individual variation in life
      satisfaction. Thus, employing a diary study of 76 fully employed, married adults
      we examined the magnitude, antecedents, and consequences of intra-individual
      variation in life satisfaction. Our findings establish a substantial amount of
      intra-individual variation, comparable to other personal evaluations assessed
      with a state approach (e.g., self-esteem), but less than that observed with major
      mood dimensions. In addition, concurrent changes in life satisfaction were
      systematically related to fluctuations in job and marital satisfaction; however,
      contrary to prediction, our results did not support a cross-level moderating role
      of Neuroticism in these associations. Our findings also lend support for the
      lagged influence of life satisfaction on next-day domain satisfaction ratings.
      Taken together, our findings demonstrate the systematic nature and importance of
      within-subject variation in life satisfaction.

PMID- 16958709
TI  - Genetic and environmental influences on Person x Situation profiles.
AB  - Genetic and environmental influences on Person x Situation interactions were
      studied using data of the German Observational Study of Adult Twins. The
      performance of 168 monozygotic and 132 dizygotic twin pairs in 15 tasks was
      observed by 120 judges who never met the twins in person. Four judges observed
      one twin of each pair in one task. Twin similarities in Person x Situation
      profiles were analyzed via (a) correlations across tasks between co-twins' Person
      x Situation profiles (their personality signatures) and (b) common-pathway
      genetic models that partitioned genetic and environmental contributions to trait
      levels and to Person x Situation interactions. Genes accounted for about 25% of
      the reliable Person x Situation interactions, whereas shared environmental
      influences were negligible.

PMID- 16958710
TI  - You may worry, but can you recognize threats when you see them?; Neuroticism,
      threat identifications, and negative affect.
AB  - The present studies sought to investigate the hedonic consequences of threat
      identification skills at low and high levels of neuroticism. Such skills were
      assessed in terms of both speed (Study 1) and accuracy (Study 2) of identifying
      threatening objects in cognitive tasks. As predicted, threat-identification
      skills interacted with trait neuroticism in predicting subjective experiences.
      Specifically, individuals high in neuroticism experienced lower levels of
      negative affect during their everyday lives if they were also skilled in
      identifying threats in the cognitive tasks (Studies 1-2). Such skills did not
      matter at low levels of neuroticism. This interactive pattern was also replicated
      in the context of life domain satisfaction (Study 2). The results support the
      view that avoidance motivation encompasses multiple component processes,
      including some that are cognitive in nature, and specifically extends self
      regulatory views of neuroticism. Of most importance, our data indicate that
      threat-identification skills can be hedonically beneficial, rather than costly,
      at high levels of neuroticism.

PMID- 16958712
TI  - A review of nursing interventions to foster becoming a mother.
AB  - OBJECTIVE: To determine the current state of knowledge of nursing interventions
      that foster the process of becoming a mother. DATA SOURCES: A literature search
      was conducted using CINAHL and PubMed electronic databases and other key
      references. STUDY SELECTION: Reports on nursing intervention research published
      in English that focused on a facet of maternal behavior in the process of
      becoming a mother during pregnancy or during the first 4 months following birth,
      or both, were included. Twenty eight reports were found. DATA EXTRACTION: Studies
      were reviewed, categorized, and analyzed and interventions synthesized to
      determine the current knowledge base for fostering becoming a mother. Categories
      included instructions for infant caregiving, building awareness of and
      responsiveness to infant interactive capabilities, promoting maternal-infant
      attachment, maternal/social role preparation, and interactive therapeutic nurse
      client relationships. DATA SYNTHESIS: Interactive therapeutic nurse-client
      relationships and maternal/social role preparation had greater impact on
      variables indicating progress in becoming a mother than formal teaching.
      Instructions without nurse input were ineffective. CONCLUSIONS: Interactive
      reciprocal nursing interventions are the most effective in enhancing mother
      infant interactions and maternal knowledge about infant care. Evidence is limited
      on how to foster the mother's feelings about herself in becoming a mother and
      attachment to her infant.

PMID- 16958713
TI  - Health care recommendations for lesbian women.
AB  - OBJECTIVE: To review research literature to provide clinicians with data-based
      recommendations for care of lesbians. DATA SOURCES: Medline searches and
      references from selected articles with the search term "lesbian health." STUDY
      SELECTION: Literature was selected whether lesbian or women who have sex with
      women was utilized as a category in the study and results were available on this
      population. DATA EXTRACTION: Data were organized according to specific health
      problems noted frequently in the research articles. DATA SYNTHESIS: Lesbians have
      previously been invisible in health services and research, but in several areas,
      data now exists on which to base care. CONCLUSIONS: Lesbians are now more
      comfortable "coming out" to providers but continue to have lower screening rates
      than other women. Risk is especially high in this population for cancer, heart
      disease, depression, and alcohol abuse. Adolescent lesbians are especially at
      risk for smoking and suicide/depression.

PMID- 16958714
TI  - Needle phobia during pregnancy.
AB  - The objective of this study was to understand the experience of a pregnant woman
      with needle phobia and examine its impact on her antepartum, intrapartum, and
      postpartum experience. A case study format was employed. A 21-year-old
      primiparous woman with diagnosed needle phobia was interviewed, and her prenatal
      and delivery records were reviewed. Three tasks during pregnancy were identified:
      seeking trusting relationships with health care providers; establishing and
      maintaining control and understanding; and coping with fear of needles, pain, and
      invasion. As frequent caregivers during childbearing, nurses with an
      understanding of needle phobia can help to establish trusting relationships with
      women with this phobia and support them and their families during childbearing
      and their encounters with needles.

PMID- 16958715
TI  - Cytokines, infections, stress, and dysphoric moods in breastfeeders and formula
      feeders.
AB  - OBJECTIVE: To analyze relationships between stress, moods, and immunity in
      breastfeeding compared to formula-feeding mothers. DESIGN: A cross-sectional
      study of 181 healthy mothers, exclusively breastfeeding or formula feeding,
      studied at 4 to 6 weeks after childbirth. SETTING: Mothers were recruited in the
      postpartum unit of the hospital and then visited in their homes once at 4 to 6
      weeks after childbirth for data collection. MAIN OUTCOME MEASURES: Stress, mood,
      infection symptoms, and serum levels of interferon-gamma and interleukin-10 were
      measured. RESULTS: Formula-feeding mothers had evidence of decreased interferon
      gamma and a decreased serum Th1/Th2 ratio (interferon-gamma/interleukin-10) when
      perceived stress, dysphoric moods, and negative life events were high, an effect
      consistent with depression of cellular immunity. However, women who were
      breastfeeding did not show these relationships. CONCLUSIONS: The data suggest
      that breastfeeding confers some psychoneuroimmunological benefit to mothers,
      perhaps through prolactin or hypothalamic-hypophyseal-adrenocortical axis stress
      refractoriness.

PMID- 16958716
TI  - Melatonin level and pattern in postpartum versus nonpregnant nulliparous women.
AB  - OBJECTIVE: To compare 24-hour melatonin level and timing in postpartum and
      nonpregnant nulliparous women. Melatonin release provides information regarding
      circadian rhythm timing, which influences health. DESIGN: 2-group comparison of
      data derived from intensive within-subject data collection. SETTING:
      Participants' typical daily environment. PARTICIPANTS: 38 postpartum and 20
      nonpregnant nulliparous women. Mothers' infants were 4 to 10 weeks of postnatal
      age. MAIN OUTCOME MEASURES: Urinary 6-sulfatoxymelatonin assayed from each
      voiding and corrected for volume using creatinine. RESULTS: Postpartum women had
      significantly higher baseline, lower maximum, lower percent rise, and differing
      pattern of 6-sulfatoxymelatonin than nonpregnant nulliparous women. CONCLUSION:
      Differences in melatonin suggest possible circadian rhythm disruption in the
      postnatal period.

PMID- 16958717
TI  - Randomized controlled trial to determine effects of prenatal breastfeeding
      workshop on maternal breastfeeding self-efficacy and breastfeeding duration.
AB  - OBJECTIVE: To determine the effects of a prenatal breastfeeding workshop on
      maternal breastfeeding self-efficacy and breastfeeding duration. DESIGN:
      Randomized controlled trial. SETTING: Large tertiary hospital in Ontario, Canada.
      PARTICIPANTS: 110 primiparous women expecting a single child, an uncomplicated
      birth, and planning to breastfeed. INTERVENTION: 2.5-hour prenatal breastfeeding
      workshop based on adult learning principles and self-efficacy theory. MAIN
      OUTCOME MEASURE: Maternal breastfeeding self-efficacy and the numbers of days and
      amount of breastfeeding were measured at four and eight weeks postpartum.
      RESULTS/DATA ANALYSIS: Over time, maternal breastfeeding self-efficacy scores
      increased in both groups. Women who attended the workshop had higher self
      efficacy scores and a higher proportion were exclusively breastfeeding compared
      to women who did not attend the workshop. There was little difference in the
      average number of days of breastfeeding, but the intervention group had less
      weaning. CONCLUSIONS: The workshop increased maternal breastfeeding self-efficacy
      and exclusive breastfeeding.

PMID- 16958718
TI  - Factors influencing women's decisions about timing of motherhood.
AB  - OBJECTIVE: To examine the factors that influence women's decisions about the
      timing of motherhood from a life span perspective. DESIGN: Qualitative. SETTING:
      Large Western Canadian city with a high rate of infants born to women aged 35
      years and older. PARTICIPANTS: 45 Canadian women aged 20 to 48 years. RESULTS:
      Independence, a stable relationship, and declining fertility influenced women's
      decisions about the timing of motherhood. Women integrated child developmental
      transitions into a projected life plan as they considered the timing of
      motherhood. Partner readiness and family of origin influences played a lesser
      role. Delayed childbearing has become more socially acceptable, with subsequent
      negative connotations associated with younger motherhood. Parental benefits have
      limited influence on the timing of motherhood. CONCLUSIONS: Recognition by nurses
      of the various and complex factors that influence women's decisions about the
      timing of motherhood may flag the importance of pregnancy-related counseling for
      woman across the fertility life span. Policy decision makers must be cognizant of
      the need for additional high-risk obstetric and neonatal health services when
      societal norms encourage women to delay childbearing in favor of completing
      education and establishing a career.

PMID- 16958719
TI  - Policies and practices for maternal support options during childbirth and
      breastfeeding initiation after cesarean in southeastern hospitals.
AB  - OBJECTIVE: To describe policies, practices, and associated rationales of hospital
      obstetric units regarding mothers' support person options during childbirth and
      to explore practices concerning support of breastfeeding initiation after
      cesarean delivery. DESIGN: Descriptive telephone survey. SETTING: Hospitals in
      the southeastern region of the United States. PARTICIPANTS: Convenience sample of
      154 obstetric nurse manager and nurse representatives employed by the
      participating hospitals. MAIN OUTCOME MEASURES: Types of policies regarding
      mothers' support person options during childbirth and immediate postpartum stage,
      initiation of breastfeeding after cesarean birth, and attitudes about policies.
      RESULTS: All hospitals allowed two or more support persons during vaginal births,
      89% permitted only one support person during nonemergent cesareans, and 58.0% of
      the nurse representatives believed that mothers should be allowed a second
      support person. Less than one third (31.2%) of the hospitals considered a
      mother's request to breastfeed in the operating room, and most (78.6%) allowed
      mothers to breastfeed in the recovery room. CONCLUSIONS: Overall, maternal
      support policies, practices, and nurse representatives' attitudes were mother and
      family friendly, particularly related to vaginal births. Though breastfeeding
      initiation after cesarean birth was encouraging, support person options during
      nonemergent cesarean births and related rationales warrant further examination.

PMID- 16958722
TI  - Nursing support of the process of becoming a mother.
AB  - In this overview, the stages in the process of becoming a mother and the
      variables influencing the process, including the mother's interacting family and
      friends, community, and societal environments, are discussed as a background for
      providing care to facilitate this process. Empathic listening and interactive
      dialogue with the mother are important approaches to identify and address her
      concerns during this important transition.

PMID- 16958723
TI  - The impact of postpartum depression on mothering.
AB  - As a rule, mothers are the primary caregivers of infants regardless of employment
      or marital status. Thus, any factors that impact mothering affect the infant and
      have public health significance. National attention is now focused on postpartum
      depression, a major variable affecting mothering. The impact of postpartum
      depression on the various components of the maternal role is described.
      Recommendations for health care practice include screening for depression across
      the first postpartum year and developing a strong network for mental health
      referrals.

PMID- 16958724
TI  - The role of Postpartum Support International in helping perinatal families.
AB  - The role of grassroots organizations in supporting new mothers is reviewed.
      Postpartum Support International is an organization that links pregnant and new
      families with mental health resources and is a key advocate for mental health
      services for childbearing women.

PMID- 16958725
TI  - Clinical assessment of mothering during infancy.
AB  - Using reliable and valid measurements of mothering can enhance clinicians' and
      researchers' ability to identify problematic patterns that pose risks to the
      health of mothers and infants during the first postpartum year. A critical review
      of observational and self-report instruments for measuring components of
      mothering is presented. Positive indicators of mothering are discussed, and
      implications for intervention and referral for problematic aspects of mothering
      are suggested.

PMID- 16958726
TI  - Contemporary mothering in a diverse society.
AB  - The contextual and environmental factors that may affect mothering and
      perceptions of the maternal role in today's increasingly diverse society are
      described. Following a historical overview of the development of maternal role
      theory within the nursing literature, the influence of images and myths in
      Western society, race/ethnicity, cultural background, and employment status are
      discussed. Guidelines for nursing interventions that allow for individual and
      cultural differences are provided.

PMID- 16958727
TI  - Opportunity knocks.

PMID- 16958728
TI  - Comparison of repair methods for ceramic-fused-to-metal crowns.
AB  - PURPOSE: The objective of this study was to evaluate the effect of four repair
      methods on the fracture load of repaired ceramic-fused-to-metal crowns. MATERIALS
      AND METHODS: Metal-ceramic crowns were fractured, and the failure load was
      measured. The fractured metal-ceramic crowns (n = 9) were assigned randomly to
      the following treatment groups: (1) hydrofluoric acid (9.5%) etching, (2) air
      particle abrasion (50 microm Al(2)O(3)), (3) silica coating (30 microm SiO(x)),
      and (4) the application of a layer of glass fiber-reinforced composite (FRC)
      (thickness: 0.12 mm) on the repair surface. The crowns were repaired with a
      highly filled resin composite and subjected to 3 repair cycles (n = 27). All
      specimens were stored in water at 37 degrees C for 24 hours and then thermocycled
      (6000 cycles, 5 degrees C to 55 degrees C). The fracture load values for final
      failure of intact and repaired crowns were measured with a universal testing
      machine, and failure types were recorded. RESULTS: No significant differences (p
      > 0.05) were found between the final failure values for the groups treated with
      9.5% hydrofluoric acid (376 N) and airborne particle abrasion with either
      Al(2)O(3) (432 N) or SiO(x) (582 N) followed by silanization, respectively.
      Significantly, higher (p < 0.0001) final failure values (885 N) were obtained
      with the use of the FRC layer when compared with the other repaired groups. There
      was no significant difference (p > 0.05) between the final fracture load of
      intact crowns (872 N) and those repaired with FRC (885 N) (One-way ANOVA with
      repeated measures, Bonferroni test). No significant difference in fracture loads
      was found between the 1st, 2nd, and 3rd repair cycles (558 N, 433 N, 485 N,
      respectively). Failure sites were predominantly at the alloy/veneering resin
      interface in Group 1; Groups 2 and 3 both showed more cohesive failures than
      Group 1. In the case of FRC, the failure pattern was exclusively cohesive between
      the two laminates of FRC layer. CONCLUSIONS: The conditioning methods (Groups 1
      to 3) of the repair surfaces did not show differences between each other; each
      resulted in mean fracture loads at lower levels than that of the intact crowns.
      Addition of an FRC layer increased the fracture load to the level of intact
      crowns. This suggests that the use of FRC in repairs of metal-ceramic crowns
      might be a viable option.

PMID- 16958729
TI  - The effect of fatigue damage on the force required to remove a restoration in a
      cement-retained implant system.
AB  - PURPOSE: To evaluate the luting agents and retentive forces before and after
      mechanical stressing. MATERIALS AND METHODS: Sample size N was 12 for each group,
      and 12 Cera-One closed-end gold cylinders were cemented with three types of
      luting cements (ImProv, UltraTemp, and TempBond). The force required to remove
      the gold cylinders from the abutments was determined with an MTS testing machine.
      After cleaning and recementing the cylinders, the samples were placed in the
      housings of an Alabama-type three-body wear machine and load of 110 N was applied
      to the gold cylinders at a frequency of 80 cycles/min for 50,000 cycles. Then
      each cylinder was pulled from its abutment and the force at which the failure
      occurred was recorded. The procedure was repeated with 300,000 cycles. RESULTS:
      Statistical analysis arising from two-way ANOVA found that the forces required to
      remove the abutments were significantly different. The most retentive cement was
      ImProv. Before cyclic loading, on average, ImProv produced a retentive value 85%
      higher than that yielded by TempBond, and 25% higher than that of UltraTemp. The
      three cements were significantly different at each of the three cycle levels.
      CONCLUSIONS: These results might suggest TempBond luting agent as the material of
      choice for provisional cementation because it allows easier removal of the
      prosthesis and maintains enough retention to prevent loosening of the
      restoration. The clinical implication is that the effect of cyclic load on the
      strength of the cements is different, an important factor in selection of a
      cement. ImProv had the highest retentive value before and after the two cycles,
      and TempBond had the lowest. UltraTemp had the highest percentage of retentive
      value lost. TempBond had no significant loss under loading even though initially
      it was the weakest.

PMID- 16958730
TI  - Effect of the association of nystatin with a tissue conditioner on its ultimate
      tensile strength.
AB  - PURPOSE: This study evaluated the ultimate tensile strength of a tissue
      conditioner without nystatin incorporation (GI-control group) and the same tissue
      conditioner modified by the addition of nystatin in two concentrations: GII
      500,000 International Units (U) and GIII-1,000,000 U, in which each milligram of
      the medicament corresponded to 6079 U. MATERIALS AND METHODS: Dumbbell-shaped
      specimens (N= 7) with a central cross-sectional area of 33 x 6 x 3 mm were
      produced for the three experimental groups. After polymerization following
      manufacturer's instructions, specimens were immersed in distilled water at 37
      degrees C for either 24 hours or 7 days and then tested in tension in the MTS 810
      at 40 mm/minute. Data were analyzed by two-way ANOVA followed by Tukey's test, at
      95% level of confidence. RESULTS: The means (force-grams (gf) +/- standard
      deviation) of the ultimate tensile strength were: GI-634.29 +/- 122.80; GII
      561.92 +/- 133.56; and GIII-547.30 +/- 73.47 for 24-hour storage, and GI-536.68
      +/- 54.71; GII-467.50 +/- 143.51; and GIII-500.62 +/- 159.76 for 7-day storage.
      There were no statistically significant differences among the three experimental
      groups (p > 0.05). The ultimate tensile strength means of all experimental groups
      after 7 days were significantly lower than those observed after 24 hours (p=
      0.04). CONCLUSIONS: The results of this study suggest that the addition of
      nystatin into the tissue conditioner investigated in concentrations below
      1,000,000 U did not affect its ultimate tensile strength.

PMID- 16958731
TI  - Effect of chemical disinfectants and repair materials on the transverse strength
      of repaired heat-polymerized acrylic resin.
AB  - PURPOSE: The purpose of this study was to evaluate both the effects of immersion
      in different chemical disinfectant solutions and the type of repair material on
      the transverse strength of repaired heat-polymerized acrylic resin. MATERIALS AND
      METHODS: A total of 110 rectangular specimens (65 x 10 x 3 mm) of heat
      polymerized acrylic resin (Triplex) were fabricated. After polymerization, the
      specimens were polished, then stored in distilled water at 37 degrees C for 1
      week. The specimens were divided into 11 groups (n = 10) coded A to K. Specimens
      of Group A remained intact (control). The specimens of Groups C to F and Groups H
      to K were immersed in the following chemical disinfectant solutions (1%, 2.5%,
      and 5.25% sodium hypochlorite and 2% glutaraldehyde, respectively) for 10
      minutes. The specimens of all groups except those of Group A were sectioned in
      the middle to create 10 mm gaps and repaired with the same resin (Groups B to F)
      and autopolymerizing acrylic resin (Groups G to K). The specimens of Groups C to
      F and Groups H to K were again immersed in the disinfectant solutions in the same
      sequence. The transverse strength (N/mm(2)) was tested for failure in a universal
      testing machine, at a crosshead speed of 5 mm/min. Two-way analysis of variance
      (ANOVA) was performed to evaluate the effects of both the disinfectant solutions
      and repair materials on the transverse strength of repaired specimens. All data
      were statistically analyzed using one-way analysis of variance followed by
      Tukey's test at 95% confidence level. RESULTS: The repaired specimens treated
      with/without disinfectant solutions showed similar (p > 0.05) transverse strength
      values. No differences (p > 0.05) were detected among the repaired specimens
      either with heat-polymerized or autopolymerizing acrylic resins. The intact
      specimens showed transverse strength values (86.9 +/- 11.8) significantly higher
      (p < 0.05) than the values of the repaired specimens. CONCLUSIONS: Among the
      repaired specimens, transverse strength was not affected after immersion in the
      disinfectants for the immersion period tested (10 min). The repair material,
      either heat-polymerized or autopolymerizing acrylic resin, had no effect on the
      transverse strength of the repaired acrylic resin specimens.

PMID- 16958732
TI  - The effect of complete dentures with a metal palate on candida species growth in
      HIV-infected patients.
AB  - PURPOSE: This in vivo investigation compared the oral candidal population between
      heat-cured acrylic resin and nickel-chromium-beryllium alloy in maxillary
      complete dentures in HIV-infected patients. MATERIALS AND METHODS: Split-palate
      maxillary complete dentures were fabricated for 19 HIV-infected patients: one
      half of the palate was made in acrylic resin and the other half in nickel
      chromium-beryllium. Patients were divided into low or high CD4+ lymphocyte count
      groups. Dentures were worn for 5 months. Palatal mucosa was clinically evaluated
      at baseline, 1, 3, and 5 months after denture insertion. Specimens were collected
      at 1, 3, and 5 months using a modified imprint culture method. Speciation of
      Candida was performed using a chromogenic culture medium. Two-sample t-test was
      employed to determine effects and significant interactions between the control
      and test groups and the low and high CD4+ lymphocyte groups. A chi(2) test
      analyzed and compared the results of the clinical evaluation (p < 0.05). RESULTS:
      Significant differences were observed in the colony counts between both materials
      during the third (p= 0.046) and fifth months (p= 0.039). The low CD4+ group
      demonstrated significant differences during the third (p= 0.03) and fifth months
      (p= 0.05). There were no significant differences between the species of Candida
      that colonized either material with the exception of Candida dubliniensis (p <
      0.001) and "Others" (p < 0.001) during the first and fifth months. There were no
      significant differences on the clinical appearance of the palatal mucosa between
      both materials (p= 1.00). CONCLUSIONS: The metal base proved to be effective in
      decreasing the fungal growth typically present in complete dentures. Although
      overt clinical manifestations were not present, colony counts of Candida species
      were high in the acrylic resin denture bases of these patients. This
      investigation demonstrated that metal base complete dentures provide an important
      alternative dental service for edentulous HIV-positive and other patients who are
      particularly prone to higher incidences of fungal infections.

PMID- 16958733
TI  - An innovative approach to chairside provisional replacement of an extracted
      anterior tooth: use of fiber-reinforced ribbon-composites and a natural tooth.
AB  - Immediate chairside replacement of an extracted anterior tooth may contribute to
      a patient's comfort, treatment acceptance, and expectations of treatment;
      however, fabrication of a custom restoration in the anterior region of the mouth
      may result in an esthetic compromise for patients during the fabrication period.
      Chairside tooth replacement is an excellent application of fiber-reinforced
      composite resin technology. This article presents an innovative, affordable
      chairside procedure in which Ribbond Multi-Purpose Bondable Reinforcement Ribbon
      is used to replace a single extracted anterior tooth using the patient's own
      tooth.

PMID- 16958734
TI  - Calcium phosphate cement: review of mechanical and biological properties.
AB  - PURPOSE: Calcium phosphate cement is a bioactive and biodegradable grafting
      material in the form of powder and liquid, which when mixed, sets as primarily
      hydroxyapatite, sometimes mixed with unreacted particles and other phases. This
      material has been extensively investigated due to its excellent biological
      properties, potential resorbability, molding capabilities, and easy manipulation.
      Because the material can potentially be replaced with bone after a period of
      time, it could retain the short-term biological advantages of hydroxyapatite
      without the long-term disadvantages. Although little is known about this material
      in the dental community, in vivo and in vitro studies show calcium phosphate
      cement as a promising material for grafting applications. In the following
      article, the authors review the biological and mechanical properties of calcium
      phosphate cement, as well as its potential use in clinical applications.
      MATERIALS AND METHODS: A Medline search was performed (timeline: 1980 to 2003)
      using the following keywords: calcium phosphate cement, hydroxyapatite cement, HA
      cement, and hydroxyapatite. The search was limited to the English language. The
      patent literature as well as a limited number of master's theses and books were
      reviewed after using the electronic database search service from a dental school
      library. RESULTS: Calcium phosphate cement appears to have excellent biological
      properties. At only 2 weeks, spicules of living bone with normal bone marrow and
      osteocytes can be seen. Excellent moldability is a desired clinical
      characteristic; however, further research is necessary in order to improve the
      mechanical properties of the cement. The resorption/replacement by bone
      capability of the cement remains controversial. Further research is needed to
      clarify this issue. Due to poor mechanical properties, clinical applications are
      currently limited to craniofacial applications. Further research is necessary to
      take advantage of the excellent biological properties of this cement under
      clinical applications. CONCLUSION: Further research is necessary to understand
      and improve the behavior of this type of cement under clinical situations.

PMID- 16958735
TI  - What marketing CAN'T do for prosthodontists.

PMID- 16958738
TI  - The effect of topical doxycycline usage on gingival crevicular fluid MMP-8 levels
      of chronic and aggressive periodontitis patients: a pilot study.
AB  - The aim of this study was to evaluate the efficacy of topical subgingival
      application of doxycycline hyclate (DH) gel adjunctive to non-surgical
      periodontal therapy on gingival crevicular fluid (GCF) matrix metalloproteinase
      (MMP)-8 levels in chronic and aggressive periodontitis patients. Forty teeth of
      10 chronic periodontitis patients and 32 teeth of eight aggressive periodontitis
      patients were screened for 6 months. Scaling and root planing (SRP) was applied
      to the control sites and DH gel adjunctive to SRP was applied to the test sites
      of each patient simultaneously. GCF MMP-8 levels were analysed at baseline, 7
      days; and at 1, 3 and 6 months by Sandwich Elisa Method. At 1, 3 and 6 months,
      probing depth (P < 0.0051) and plaque scores and bleeding on probing values (P =
      0.000) significantly decreased in each group when compared with the baseline, but
      there was no statistically significant difference between the test and control
      sites. GCF MMP-8 levels reduced presenting statistically significant differences
      on 7 days, 1, 3 and 6 months in four of the groups (P < 0.05); however,
      intergroup differences were not statistically significant. Developing functional
      and immunological-based chair-side MMP tests might serve as useful adjunctive
      diagnostic tools when monitoring the effects of DH gel application.

PMID- 16958739
TI  - Dentinal sensitivity: a natural mineral dietary supplement study.
AB  - The purpose of the investigation was to determine the effect of drinking a
      natural mineral dietary supplement (NMDS) on gingival health and dentinal
      hypersensitivity. The NMDS product was from a geothermal source and contained 3.6
      mg l(-1) of fluoride and other minerals. Sample selection included subjects with
      gingival inflammation and sensitivity as well as screening for exclusion factors.
      A double-blind randomized parallel approach was used. The investigation was a
      quasi-experimental pre/post-test design. The experimental group ingested and
      swished twice a day with the NMDS (1 l) and the control group followed the same
      regimen with a placebo containing de-ionized water (DIW). Clinical measurements
      of gingival inflammation and dentinal sensitivity were taken at baseline, 4 and 8
      weeks. Gingival inflammation was measured using the Gingival Index. Dentinal
      hypersensitivity was measured using a tactile stimulus and an evaporative
      stimulus. After each stimulus was applied, the subjects rated the amount of
      discomfort on a visual analogue scale from 0 to 10. Each set of data was analysed
      using anova and a post hoc probing technique to determine within- and between
      group differences (P = 0.05). The experimental and control groups (n = 70)
      experienced a statistically significant decrease in tactile and evaporative
      sensitivity scores over time; however, the between-group differences were not
      significant. The gingival inflammation data were not statistically significant
      with regard to the within- and between-group differences. Therefore the NMDS and
      DIW were equally effective in reducing dentinal hypersensitivity and neither
      product effectively reduced gingival inflammation.

PMID- 16958740
TI  - Measurement of stain removal in vitro: a comparison of two instrumental methods.
AB  - AIM: The aim of this study was to compare an established spectrophotometrical
      approach for the measurement of stain removal in vitro with a new digital image
      analysis system. METHOD: Eighteen acrylic blocks were stained by cycling them
      through human saliva (2 min), chlorhexidine (2 min) and tea (1 h), rinsed with
      deionized water and left to air dry. The absorbance of each block was then
      measured at 395 nm using a single-beam spectrophotometer. The lightness (L-value)
      of the stained blocks (after a baseline correction) was measured using digital
      image analysis. Image acquisition and L-values were obtained using Adobe
      Photoshop software. The stain removal ability of two whitening toothpastes and
      deionized water was tested by immersing each stained block in a test slurry (15 g
      paste/60 ml deionized water) for 1 min, rinsing and finally left to air dry. This
      cycle was repeated until the blocks had 5 min exposure to the slurry. Absorbance
      values from spectrophotometry and L-values by image analysis were obtained after
      each cycle. RESULTS: Fleiss' coefficient of reliability for intra-operator
      repeatability of the image analysis system and spectrophotometry was 0.999 for
      both methods which shows excellent reliability. Pearson's correlation
      coefficients for the two methods (stain build-up) were 0.976. Test products A, B
      and C gave correlations of 0.962, 0.998 and 0.817 respectively (stain removal),
      significant at the 0.01 level. CONCLUSION: The image system is a reliable
      alternative measurement method validated here against spectrophotometry for stain
      removal in vitro, and can provide full colour measurement.

PMID- 16958741
TI  - Does fluoride rinsing have an effect on teeth status? Evaluation of preventive
      dental health activities for the youth of Woudenberg, The Netherlands.
AB  - Surveys among primary school children of group 8 (mainly 12-year olds) in
      1988/1989 and 1995/1996 revealed that the dental status in Woudenberg was worse
      than in other municipalities in the Eemland region. Therefore, several dental
      preventive activities were started in Woudenberg for children aged 0-12 years.
      This included fluoride rinsing and teeth brushing lessons at primary schools. So
      as to evaluate the effect of these school activities, a new survey was carried
      out in Woudenberg in 2004. The teeth status (DMF-S value, percentage sound teeth,
      percentage erosion) was investigated by examination. Information regarding dental
      hygiene behaviour and participation in teeth brushing lessons was obtained by
      questionnaire. Teeth status (measured by DMF-S value as well as percentage sound
      teeth) at rinsing schools in 2004 was significantly better than at the same
      schools in 1995/1996. Multivariate analyses revealed that fluoride rinsing for at
      least 3 years (besides educational level of parents) is the most determining
      factor for teeth status independent of other variables. Pupils who never rinsed
      with fluoride were almost four times more likely to have caries lesions than
      pupils who rinsed for at least 3 years. This study strongly indicates that long
      term rinsing with fluoride has a positive effect on teeth status.

PMID- 16958742
TI  - A thin or thick probe handle: does it make a difference?
AB  - OBJECTIVES: The aim of the present study was to assess the probing force exerted
      when using two manual periodontal probes with different handle diameters in hands
      of different dental professionals. METHODS: For this study two periodontal probes
      with handle diameters of 54 and 92 mm were used. The 11 subjects responsible for
      the measurements were periodontists, postgraduate periodontal students and dental
      hygienists. Per measurement session, 20 measurements were performed by each
      subject. Each probe was used 10 times. After the first baseline measurement
      session, a second session was performed 1 week later and a last third session
      another 3 weeks later. Orders for using each probe were randomized for each
      subject and each session. RESULTS: The mean overall force with the thin probe was
      55.2 g and with the thick probe 59.4 g. The difference of 4.2 g between the two
      probe types was found to be statistically significant (P = 0.041). CONCLUSION:
      The present study showed that the diameter of the probe handle also had an effect
      on the force exerted with a periodontal probe. However, the clinical relevance of
      this difference may be minor, when considering the interindividual variance of
      forces exerted when probing.

PMID- 16958743
TI  - Parental oral health care of mentally retarded children in Ilala municipality,
      Dar es Salaam, Tanzania.
AB  - OBJECTIVE: The aim of this study was to investigate oral hygiene practices and
      oral health care given by parents to mentally retarded children in Dar es Salaam,
      Tanzania. METHODS: A total of 140 questionnaires were distributed; only 100
      questionnaires were completed and thus were included in the analysis, a 71.4%
      response rate. Questionnaires inquired on oral hygiene practices, supervision or
      assistance during tooth brushing, examination of the oral cavity, and measures
      taken in an event of oral health problems. RESULTS: Sixty-five per cent of the
      children are able to brush their teeth, whereas 35% are brushed by a family
      member. About 74% of the children who brush themselves brush occasionally or once
      per day while 26% brush more than once per day. More than 58% of the children who
      brush themselves brush under supervision. A statistically significant difference
      was observed in respect of bleeding on brushing which was among 61% of the
      children who brush occasionally or once per day and among 29% of the children who
      brush more than once per day (Pearson chi2 = 5.13, P = 0.024). Sixty-four per
      cent of parents occasionally examine their children's oral cavity. Few parents
      take their children to a dentist in an event of toothache/cavity on a tooth (26%)
      or bleeding on brushing (37%). CONCLUSION: Most children are able to brush their
      teeth themselves. Majority of those who cannot brush are assisted. Bleeding on
      brushing and tooth cavities are common problems but few children are taken to a
      dentist for care.

PMID- 16958744
TI  - Dental plaque, caries prevalence and gingival conditions of 14-15-year-old
      schoolchildren in Jerash District, Jordan.
AB  - The aim of this cross-sectional study was to evaluate oral hygiene, gingival
      condition and dental caries prevalence in 14-15-year-old school children in
      Jerash District, Northern Jordan. Twenty schools (10 male and 10 female schools)
      with 1362 children of eighth and ninth grades were randomly selected and
      incorporated in this study. All participants had dental examinations for oral
      hygiene, gingival condition and dental caries experience using the Silness and
      Loe Plaque Index (PI), Loe and Silness Gingival Index (GI), and decayed (D),
      missing (M) and filled (F) teeth (DMFT) and surface (DMFS) codes respectively.
      The results showed that males had significant lower plaque but significantly
      higher gingival scores than females (P < 0.001). About 24% of children were
      caries-free. The proportions of children with one, two or three decayed teeth
      were between 10% and 18%. Slight non-significant variations between males and
      females were observed in regard to DMFT/S and their components (P < 0.05). It is
      concluded that significant gender variations were noted in PI and GI scores but
      not in DMFT/S or their components. However, the values of these clinical scores
      were lower than those results previously reported in northern Jordan.

PMID- 16958745
TI  - Theoretical and practical considerations for the development of online
      international collaborative learning for dental hygiene students.
AB  - Globalization and concurrent development in computer and communication technology
      has increased interest in collaborative online teaching and learning for students
      in higher education institutions. Many institutions and teachers have introduced
      computer-supported programmes in areas including dental hygiene. The potential
      for the use of this technology is exciting; however, its introduction should be
      careful and considered. We suggest that educators wanting to introduce computer
      supported programmes make explicit their pedagogical principles and then select
      technologies that support and exploit these principles. This paper describes this
      process as it was applied to the development of an international web-based
      collaborative learning programme for dental hygiene students.

PMID- 16958746
TI  - Secretion rate and amylase concentration of whole saliva after consumption of
      beer.

PMID- 16958747
TI  - Healthy mother, healthy baby.

PMID- 16958749
TI  - A square archaeon, the smallest eukaryote and the largest bacteria.

PMID- 16958751
TI  - Evaluation of denaturing gradient gel electrophoresis to differentiate
      Escherichia coli populations in secondary environments.
AB  - The development of methodology to differentiate mixed populations of Escherichia
      coli in the secondary habitat might improve monitoring of fecal pollution
      indicators and facilitate the development of strategies to mitigate bacterial
      pollution. The objective of this study was to determine the ability of denaturing
      gradient gel electrophoresis (DGGE) to differentiate mixed assemblages of E. coli
      in the natural environment. After confirming the identity of 184 environmental
      bacterial isolates as E. coli, each was subjected to polymerase chain reaction
      (PCR) of the beta-glucuronidase gene (uidA) followed by DGGE fingerprinting. The
      ability of DGGE to discriminate individual isolates at the strain level was
      determined by comparing fingerprints to those resulting from a standard, library
      dependent fingerprinting method, BOX-PCR. Computerized analysis of fingerprints
      indicated that DGGE and BOX-PCR identified 15 and 21 unique phylotypes
      respectively. Rank-abundance plots comparing the numerical distribution of unique
      E. coli phylotypes detected by both methods revealed no difference in resolution
      at the population level. In water and sediment samples from two beaches, DGGE
      effectively distinguished indigenous E. coli populations with an average rate of
      correct classification (site-based) of 83%. Denaturing gradient gel
      electrophoresis of uidA genes isolated and PCR-amplified from environmental
      samples appears to be an effective tool to differentiate unique E. coli
      populations and should be useful to characterize E. coli dynamics in the
      secondary environment.

PMID- 16958750
TI  - Detection of glycolate oxidase gene glcD diversity among cultured and
      environmental marine bacteria.
AB  - Of eight laboratory cultures of marine gamma- and alpha-Proteobacteria tested,
      growth on glycolate as a sole carbon source was detected for only three species:
      Pseudomonas stutzeri, Oceanimonas doudoroffii and Roseobacter sp. isolate Y3F.
      Degenerate polymerase chain reaction (PCR) primers were designed to amplify glcD,
      which encodes the D-subunit of the enzyme glycolate oxidase; glcD could be
      amplified only from those cultures that grew on glycolate. The PCR primers were
      used to explore glcD diversity in four field samples collected from different
      ocean environments: an Atlantic Gulf Stream Ring, sampled above and below the
      thermocline and two Pacific coastal sites, Parks Bay and San Juan Channel, WA.
      Environmental glcD sequences belonged to six major bacterial phylogenetic groups,
      with most sequences forming novel clades with no close relatives. Different
      patterns of glcD diversity were observed within and between the two nutrient
      regimes. Comparison of glcD and 16S rDNA diversity and analyses of available
      bacterial genomes and a metgenomic library from the Sargasso Sea show that
      glycolate-utilizing potential exists in only a subset of bacteria. Glycolate is
      produced in marine environments mainly by phytoplankton. Examination of glcD
      diversity will aid in understanding the influence of phytoplankton on bacterial
      community structure.

PMID- 16958752
TI  - The in situ physiology of Skermania piniformis in foams in Australian activated
      sludge plants.
AB  - The in situ physiology of the filamentous bacterium Skermania piniformis
      frequently seen in activated sludge foams in Australia was investigated. An
      oligonucleotide probe, Spin1449, targeting the 16S rRNA of S. piniformis was
      designed for its identification by fluorescence in situ hybridization (FISH),
      validated with pure cultures and applied successfully to foam samples from two
      geographically distant Australian plants. While filaments of this bacterium
      appeared to be comparatively hydrophobic, the organism had no clear preference
      for hydrophobic or hydrophilic substrates. In both foams examined using
      microautoradiography (MAR), filaments selectively took up substrates under
      aerobic and anoxic (NO(3) (-)) but not anaerobic or anoxic (NO(2) (-))
      conditions. Skermania piniformis assimilated oleic acid, palmitic acid, glycerol
      and glycine. Ectoenzyme activities detected suggest that S. piniformis has an
      ability to assimilate a greater range of substrates than might be concluded from
      the MAR data obtained here. Based on the substrate uptake data presented here, an
      anaerobic selector may work for controlling S. piniformis in activated sludge
      systems.

PMID- 16958753
TI  - Application of a nifH oligonucleotide microarray for profiling diversity of N2
      fixing microorganisms in marine microbial mats.
AB  - Diazotrophic community structure in microbial mats from Guerrero Negro (GN), Baja
      California, Mexico, was studied using polymerase chain reaction amplification of
      the nifH gene and a newly developed nifH oligonucleotide microarray. Ninety-six
      oligonucleotide probes designed for nifH sequences from cultivated isolates and
      the environment were printed on glass microarrays. Phylogenetic analysis showed
      that the probes represented all of the main nifH clusters. Specificity was tested
      by (i) evaluation of cross hybridization using individual targets, and (ii)
      comparison of the observed hybridization signals and those predicted from the
      sequences cloned from microbial mats. Signal intensity had a positive
      relationship with target concentration and the percentage identity between probe
      and target. Under moderate stringency and high target concentration, specificity
      of the probes varied from 77% to 100% with the individual targets tested. At the
      end of a 7-month long nutrient manipulation experiment in GN microbial mats, no
      expression of nitrogen fixation under nitrogen loading was detected, although a
      diverse community of diazotrophs was detected. The diversity in diazotrophic
      population present was higher than in the population expressing the nifH gene,
      and there were taxa specific differences in response to nutrients. The nifH
      microarray is a powerful tool for diazotroph community analysis in the marine
      environment.

PMID- 16958754
TI  - Identification and quantification of uncultivated Proteobacteria associated with
      pyrene degradation in a bioreactor treating PAH-contaminated soil.
AB  - Uncultivated bacteria associated with the degradation of pyrene in a bioreactor
      treating soil contaminated with polycyclic aromatic hydrocarbons (PAH) were
      identified by DNA-based stable-isotope probing (SIP) and quantified by real-time
      quantitative PCR. Most of the 16S rRNA gene sequences recovered from (13)C
      enriched DNA fractions clustered phylogenetically within three separate groups of
      beta- and gamma-Proteobacteria unassociated with described genera and were
      designated "Pyrene Groups 1, 2 and 3". One recovered sequence was associated with
      the Sphingomonas genus. Pyrene Groups 1 and 3 were present in very low numbers in
      the bioreactor but represented 75% and 7%, respectively, of the sequences
      recovered from 16S rRNA gene clone libraries constructed from (13)C-enriched DNA.
      In a parallel time-course incubation with unlabelled pyrene, there was between a
      2- and 4-order-of-magnitude increase in the abundance of 16S rRNA genes from
      Pyrene groups 1 and 3 and from targeted Sphingomonas spp. over a 10 day
      incubation. Sequences from Pyrene Group 2 were 11% of the SIP clone libraries but
      accounted for 14% of the total bacterial 16S rRNA genes in the bioreactor
      community. However, the abundance of this group did not increase significantly in
      response to pyrene disappearance. These data indicate that the primary pyrene
      degraders in the bioreactor were uncultivated, low-abundance beta- and gamma
      Proteobacteria not previously associated with pyrene degradation.

PMID- 16958755
TI  - Analysis of mercuric reductase (merA) gene diversity in an anaerobic mercury
      contaminated sediment enrichment.
AB  - The reduction of ionic mercury to elemental mercury by the mercuric reductase
      (MerA) enzyme plays an important role in the biogeochemical cycling of mercury in
      contaminated environments by partitioning mercury to the atmosphere. This
      activity, common in aerobic environments, has rarely been examined in anoxic
      sediments where production of highly toxic methylmercury occurs. Novel degenerate
      PCR primers were developed which span the known diversity of merA genes in Gram
      negative bacteria and amplify a 285 bp fragment at the 3' end of merA. These
      primers were used to create a clone library and to analyse merA diversity in an
      anaerobic sediment enrichment collected from a mercury-contaminated site in the
      Meadowlands, New Jersey. A total of 174 sequences were analysed, representing 71
      merA phylotypes and four novel MerA clades. This first examination of merA
      diversity in anoxic environments suggests an untapped resource for novel merA
      sequences.

PMID- 16958756
TI  - Widespread distribution and high abundance of Rhizobium radiobacter within
      Mediterranean subsurface sediments.
AB  - Eastern Mediterranean sediments are characterized by the occurrence of distinct,
      organic-rich layers, called sapropels. These harbour elevated microbial numbers
      in comparison with adjacent carbon-lean intermediate layers. A recently obtained
      culture collection from these sediments was composed of 20% of strains closely
      related to Rhizobium radiobacter, formerly classified as Agrobacterium
      tumefaciens. To prove and quantify the in situ abundance of R. radiobacter, a
      highly specific quantitative polymerase chain reaction (PCR) protocol was
      developed. To convert quantification results into cell numbers, the copy number
      of rrn operons per genome was determined. Southern hybridization showed that our
      isolates contained four operons. Finally, quantitative PCR was applied to 45
      sediment samples obtained across the eastern Mediterranean. Rhizobium radiobacter
      was present in 38 of 45 samples indicating an almost ubiquitous distribution. In
      total, 25-40 000 cells per gram of sediment were detected, corresponding to 0.001
      5.1% of the bacterial cells. In general, the relative and absolute abundance of
      R. radiobacter increased with depth and was higher in sapropels than in
      intermediate layers. This indicates that R. radiobacter forms an active
      population in up to 200 000 years old sapropels. The present study shows for the
      first time that a cultivated subsurface bacterium is highly abundant in this
      environment.

PMID- 16958757
TI  - Inactivation of the Pseudomonas putida cytochrome o ubiquinol oxidase leads to a
      significant change in the transcriptome and to increased expression of the CIO
      and cbb3-1 terminal oxidases.
AB  - Pseudomonas putida KT2440 contains a branched aerobic respiratory chain with
      several terminal oxidases. Inactivation of the cyo terminal ubiquinol oxidase has
      little effect on growth rate but is known to relieve the inhibition by global
      control that modulates induction of genes required to assimilate alkanes in cells
      growing in the presence of preferred carbon sources. We show that inactivation of
      other terminal oxidases has no effect on regulation of the alkane degradation
      pathway, which points to cyo as the oxidase that transmits a regulatory signal
      related to the activity of the electron transport chain. Using a genome-wide DNA
      microarray we found that inactivation of cyo has a significant effect on the
      transcriptome, supporting that it participates in global regulation of gene
      expression. Among the genes affected stand out those coding for transporters of
      organic acids, porins, transcriptional regulators and terminal oxidases. Real
      time reverse transcription polymerase chain reaction (RT-PCR) showed that, in
      cells growing exponentially in a complete medium, the absence of cyo was
      compensated by increased expression of the cyanide-insensitive and cbb3-1
      terminal oxidases, while cbb3-2 and aa3 oxidases remained unaffected. When cells
      enter into stationary phase cyo levels decrease and inhibition of the alkane
      degradation genes ceases. This was paralleled by upregulation of the cyanide
      insensitive, cbb3-1, cbb3-2 and aa3 terminal oxidases. The results suggest that
      P. putida adapts the composition of the electron transport chain not only to
      optimize energy generation, but also to influence the transcriptome profile of
      the cell through global control of gene expression.

PMID- 16958758
TI  - Rapid estimation of microbial numbers in water using bulk fluorescence.
AB  - Enumeration of microbial cells without culturing is an essential technique for
      microbial ecology and water quality evaluation. Here we show that bulk
      fluorescence using the SYBR Gold DNA stain can be used to rapidly quantify
      microbial cells per millilitre in fresh, marine and estuarine waters. The bulk
      fluorescence method is comparable to estimating cell concentrations in cultures
      using optical density; however, this enhanced method enables the user to estimate
      microbial numbers at lower concentration (> 10(5) cells ml(-1)) found in
      environmental samples. The technique worked in both single-cell and 96-well plate
      fluorescent spectrophotometers. Differences of approximately 10(5) cells per
      millilitre were discernible and the precision of the bulk fluorescence was higher
      than direct counting by epifluorescent microscopy. Treatment with DNase I
      increased sensitivity by lowering background noise attributed to free DNA. This
      technique is simple, rapid, inexpensive and adaptable for automatically
      estimating microbial numbers in water samples.

PMID- 16958759
TI  - Prokaryotic diversity and metabolically active microbial populations in sediments
      from an active mud volcano in the Gulf of Mexico.
AB  - In this study, ribosomes and genomic DNA were extracted from three sediment
      depths (0-2, 6-8 and 10-12 cm) to determine the vertical changes in the microbial
      community composition and identify metabolically active microbial populations in
      sediments obtained from an active seafloor mud volcano site in the northern Gulf
      of Mexico. Domain-specific Bacteria and Archaea 16S polymerase chain reaction
      primers were used to amplify 16S rDNA gene sequences from extracted DNA.
      Complementary 16S ribosomal DNA (crDNA) was obtained from rRNA extracted from
      each sediment depth that had been subjected to reverse transcription polymerase
      chain reaction amplification. Twelve different 16S clone libraries, representing
      the three sediment depths, were constructed and a total of 154 rDNA (DNA-derived)
      and 142 crDNA (RNA-derived) Bacteria clones and 134 rDNA and 146 crDNA Archaea
      clones obtained. Analyses of the 576 clones revealed distinct differences in the
      composition and patterns of metabolically active microbial phylotypes relative to
      sediment depth. For example, epsilon-Proteobacteria rDNA clones dominated the 0-2
      cm clone library whereas gamma-Proteobacteria dominated the 0-2 cm crDNA library
      suggesting gamma to be among the most active in situ populations detected at 0-2
      cm. Some microbial lineages, although detected at a frequency as high as 9% or
      greater in the total DNA library (i.e. Actinobacteria, alpha-Proteobacteria),
      were markedly absent from the RNA-derived libraries suggesting a lack of in situ
      activity at any depth in the mud volcano sediments. This study is one of the
      first to report the composition of the microbial assemblages and physiologically
      active members of archaeal and bacterial populations extant in a Gulf of Mexico
      submarine mud volcano.

PMID- 16958760
TI  - Chemotaxis of Ralstonia sp. SJ98 towards p-nitrophenol in soil.
AB  - Bioremediation of contaminated sites has been accepted as an efficient and
      cheaper alternative to physicochemical means of remediation in several cases.
      Although chemotactic behaviour of many bacteria has been studied earlier and
      assays have been developed to study bacterial chemotaxis in semi-solid media,
      this phenomenon has never been demonstrated in soil. For bioremediation
      application it is important to know whether bacteria actually migrate through the
      heterogenous soil medium towards a gradient of a particular chemoattractant. In
      the present study we have successfully demonstrated bacterial chemotaxis of a
      Ralstonia sp. SJ98 in soil microcosm using qualitative and quantitative plate and
      tray assays. The migration of bacteria has been established using several methods
      such as plate counting, vital staining and flow cytometry and slot blot
      hybridization. A non-chemotactic p-nitrophenol utilizing strain Burkholderia
      cepacia RKJ200 has been used as negative control. Our work clearly substantiates
      the hypothesis that chemotactic bacteria may enhance in situ bioremediation of
      toxic pollutants from soils and sediments.

PMID- 16958761
TI  - Microarray and genetic analysis of electron transfer to electrodes in Geobacter
      sulfurreducens.
AB  - Whole-genome analysis of gene expression in Geobacter sulfurreducens revealed 474
      genes with transcript levels that were significantly different during growth with
      an electrode as the sole electron acceptor versus growth on Fe(III) citrate. The
      greatest response was a more than 19-fold increase in transcript levels for omcS,
      which encodes an outer-membrane cytochrome previously shown to be required for
      Fe(III) oxide reduction. Quantitative reverse transcription polymerase chain
      reaction and Northern analyses confirmed the higher levels of omcS transcripts,
      which increased as power production increased. Deletion of omcS inhibited current
      production that was restored when omcS was expressed in trans. Transcript
      expression and genetic analysis suggested that OmcE, another outer-membrane
      cytochrome, is also involved in electron transfer to electrodes. Surprisingly,
      genes for other proteins known to be important in Fe(III) reduction such as the
      outer-membrane c-type cytochrome, OmcB, and the electrically conductive pilin
      "nanowires" did not have higher transcript levels on electrodes, and deletion of
      the relevant genes did not inhibit power production. Changes in the transcriptome
      suggested that cells growing on electrodes were subjected to less oxidative
      stress than cells growing on Fe(III) citrate and that a number of genes annotated
      as encoding metal efflux proteins or proteins of unknown function may be
      important for growth on electrodes. These results demonstrate for the first time
      that it is possible to evaluate gene expression, and hence the metabolic state,
      of microorganisms growing on electrodes on a genome-wide basis and suggest that
      OmcS, and to a lesser extent OmcE, are important in electron transfer to
      electrodes. This has important implications for the design of electrode materials
      and the genetic engineering of microorganisms to improve the function of
      microbial fuel cells.

PMID- 16958762
TI  - Ice-active characteristics of soil bacteria selected by ice-affinity.
AB  - As an initial screen for microorganisms that produce ice-active macromolecules,
      ice-affinity was used to select microorganisms from soil consortia originating
      from three temperate regions. Once selected and subsequently purified to single
      colonies, these microbes were putatively identified by 16S ribosomal RNA
      sequencing and assayed for various ice-active properties. Ice-affinity selection
      appeared to select for bacteria with ice-associating activities: inhibition of
      ice recrystallization; ice nucleation; ice shaping. Although none of these
      activities were observed in Paenibacillus amyloliticus C8, others such as
      Chryseobacterium sp. GL8, demonstrated both ice recrystallization inhibition and
      ice-shaping activities. Pseudomonas borealis DL7 was classified as a type I ice
      nucleator, Flavobacterium sp. GL7, was identified as a type III ice nucleator and
      Acinetobacter radioresistens DL5 demonstrated ice recrystallization inhibition.
      In all, 19 different culturable bacteria were selected from the thousands of
      microbes in late-summer collected soil samples. Many of the selected microbes
      have been previously reported in glacial ice cores or polar sea ice, and of five
      isolates that were further characterized, four showed ice-associating activities.
      These results indicate the significant potential of ice-affinity selection even
      with temperate climate soils, suggesting that sampling in more extreme and remote
      areas is not required for the isolation of ice-active bacteria.

PMID- 16958763
TI  - The F1F0-ATPase of Bifidobacterium animalis is involved in bile tolerance.
AB  - Adaptation and tolerance to bile stress are important factors for the survival of
      bifidobacteria in the intestinal tract. Bifidobacterium animalis is a probiotic
      microorganism which has been largely applied in fermented dairy foods due to its
      technological properties and its health-promoting effects for humans. The effect
      of the presence of bile on the activity and expression of F(1)F(0)-ATPase, the
      pool of ATP and the intracellular pH of B. animalis IPLA 4549 and its mutant with
      acquired resistance to bile B. animalis 4549dOx was determined. The bile
      resistant mutant tolerated the acid pH better than its parent strain. Bile
      induced the expression of the F(1)F(0)-ATPase and increased the membrane-bound
      H(+)-ATPase activity, in both parent and mutant strains. In acidic conditions (pH
      5.0), the expression and the activity of this enzyme were higher in the mutant
      than in the parent strain when cells were grown in the absence of bile. Total ATP
      content was higher for the mutant in the absence of bile, whereas the presence of
      bile induced a decrease of intracellular ATP levels, which was much more
      pronounced for the parent strain. At pH 4.0, and independently on the presence or
      absence of bile, the mutant showed a higher intracellular pH than its parent
      strain. These findings suggest that the bile-adapted B. animalis strain is able
      to tolerate bile by increasing the intracellular ATP reserve, and by inducing
      proton pumping by the F(1)F(0)-ATPase, therefore tightly regulating the internal
      pH, and provide a link between the physiological state of the cell and the
      response to bile.

PMID- 16958765
TI  - Aerobic and anaerobic methanotrophs in the Black Sea water column.
AB  - Inputs of CH(4) from sediments, including methane seeps on the continental margin
      and methane-rich mud volcanoes on the abyssal plain, make the Black Sea the
      world's largest surface water reservoir of dissolved methane and drive a high
      rate of aerobic and anaerobic oxidation of methane in the water column. Here we
      present the first combined organic geochemical and molecular ecology data on a
      water column profile of the western Black Sea. We show that aerobic methanotrophs
      type I are responsible for methane oxidation in the oxic water column and ANME-1-
      and ANME-2-related organisms for anaerobic methane oxidation. The occurrence of
      methanotrophs type I cells in the anoxic zone suggests that inactive cells settle
      to deeper waters. Molecular and biomarker results suggest that a clear
      distinction between the occurrence of ANME-1- and ANME-2-related lineages exists,
      i.e. ANME-1-related organisms are responsible for anaerobic methane oxidation
      below 600 m water depth, whereas ANME-2-related organisms are responsible for
      this process in the anoxic water column above approximately 600 m water depth.

PMID- 16958764
TI  - Study of nitrogen fixation in microbial communities of oil-contaminated marine
      sediment microcosms.
AB  - Aerobic microbial degradation of pollutant oil (petroleum) in aquatic
      environments is often severely limited by the availability of combined nitrogen.
      We therefore studied whether the microbial community enriched in marine sediment
      microcosms with an added oil layer and exposure to light harboured nitrogenase
      activity. The acetylene reduction (AR) assay indeed indicated active nitrogenase;
      however, similar activity was observed in oil-free control microcosms. In both
      microcosms, the AR rate was significantly reduced upon a dark shift, indicating
      that enriched cyanobacteria were the dominant diazotrophs. Analysis of structural
      dinitrogenase reductase genes (nifH) amplified from both microcosms indeed
      revealed NifH sequences related mostly to those of heterocystous cyanobacteria.
      NifH sequences typically affiliating with those of heterotrophic bacteria were
      more frequently retrieved from the oil-containing sediment. Expression analyses
      showed that mainly nifH genes similar to those of heterocystous cyanobacteria
      were expressed in the light. Upon a dark shift, nifH genes related to those of
      non-heterocystous cyanobacteria were expressed. Expression of nifH assignable to
      heterotrophs was apparently not significant. It is concluded that cyanobacteria
      are the main contributors of fixed nitrogen to oil-contaminated and pristine
      sediments if nitrogen is a limiting factor and if light is available. Hence, also
      the oil-degrading heterotrophic community may thus receive a significant part of
      combined nitrogen from cyanobacteria, even though oil vice versa apparently does
      not stimulate an additional nitrogen fixation in the enriched community.

PMID- 16958768
TI  - 2004 American Academy of Nurse Practitioners National Nurse Practitioner Sample
      Survey: focus on acute care.

PMID- 16958766
TI  - Anaerobic ammonium oxidation in a tropical freshwater system (Lake Tanganyika).
AB  - Here we provide the first direct evidence for the anammox process (anaerobic
      ammonium oxidation) in a lacustrine system, Lake Tanganyika, the second largest
      lake in the world. Incubations with (15)N labelled nitrate showed that anammox
      occurred in the suboxic water layer at 100-110 m water depth. Anammox rates up to
      10 nM N(2) h(-1) are comparable to those reported for the marine water column. Up
      to approximately 13% of produced N(2) could be attributed to the anammox process
      whereas the remainder was related to denitrification. Typical lipid biomarkers
      characteristic of anammox bacteria were found in filtered water from the depths
      where anammox occurred, thus supporting the presence of anammox bacteria. Further
      evidence is provided by fluorescence in situ hybridization (FISH), revealing up
      to 13 000 anammox bacteria cells per ml or 1.4% of all DAPI (4'-6-Diamidino-2
      phenylindole)-stained cells. Phylogenetic analyses of partial 16S rRNA genes
      indicated the presence of sequences most closely related to the known anammox
      bacterium Candidatus "Scalindua brodae" (95.7% similarity). Using the incubation
      results, a total loss of 0.2 Tg N(2) per year linked to anammox was estimated for
      the Northern basin of Lake Tanganyika.

PMID- 16958769
TI  - The case presentation as argument.

PMID- 16958770
TI  - Cochlear implantation in children: implications for the primary care provider.
AB  - PURPOSE: To define hearing loss (HL), discuss the impact of HL on child
      development, and review the literature on cochlear implantation in children. The
      criteria for and the benefits and limitations of cochlear implantation in
      children, as well as the implications for the primary care provider with regard
      to children who have cochlear implants, are presented. DATA SOURCES: Review of
      published literature on the topic. CONCLUSIONS: A child's future development
      depends greatly on speech and language skills. Any type of HL can impact and may
      even hinder speech and language acquisition. It is therefore crucial to enforce
      early identification of HL. For severe to profoundly hearing-impaired children,
      cochlear implantation serves as an avenue for hearing and language development.
      IMPLICATIONS FOR PRACTICE: Nurse practitioners ought to be up to date with
      criteria for and the benefits and risks of cochlear implantation. Health-related
      issues, such as vaccination, otitis media, and meningitis, must be assessed for
      and managed promptly.

PMID- 16958771
TI  - Assessing military veterans for posttraumatic stress disorder: a guide for
      primary care clinicians.
AB  - PURPOSE: To educate primary care providers on the physical effects of
      posttraumatic stress disorder (PTSD), explain why military veterans are at great
      risk, and describe how to identify PTSD in primary care clients. DATA SOURCES:
      Current scientific and psychiatric literature on PTSD. CONCLUSIONS: PTSD is
      prevalent in the military community because of the frequency and type of trauma
      seen in the combat zone. With the ongoing military deployments, assessment for
      the presence of PTSD is increasingly important for comprehensive and high-quality
      primary care. Clients with trauma histories, such as veterans, are at increased
      risk for physical disorders such as heart disease and psychological disorders
      such as anxiety, depression, and PTSD. IMPLICATIONS FOR PRACTICE: Primary care
      clinicians, including those outside the military health system, are essential in
      identifying trauma histories and directing clients to appropriate care.

PMID- 16958772
TI  - Office-based spirometry for early detection of obstructive lung disease.
AB  - PURPOSE: To review the research-based evidence supporting smoking cessation as
      the only proven method to reduce chronic obstructive pulmonary disease (COPD)
      progression and to show that early detection of disease with office-based
      spirometry can lead to therapeutic intervention before physiologic symptoms
      arise. DATA SOURCES: Extensive review of national and international scientific
      literature supplemented with drawings and algorithms. CONCLUSIONS: Early
      detection of COPD with spirometry, along with smoking cessation, and aggressive
      intervention can alter the insidious course of this highly preventable disease.
      It is imperative that nurse practitioners utilize this simple and inexpensive
      procedure to identify COPD in its earliest stages, so treatment can reduce
      individual and community disease burden, reduce morbidity and mortality, and help
      reduce healthcare costs. IMPLICATIONS FOR PRACTICE: Determination of early
      airflow obstruction supports smoking cessation education, provides objective data
      for patient motivation, thereby doubling patient compliance and reducing further
      disease burden.

PMID- 16958773
TI  - Homecare issues in rotavirus gastroenteritis.
AB  - PURPOSE: This article will describe the burden of rotavirus gastroenteritis (RGE)
      and its management, highlighting educational issues that nurse practitioners can
      assist caregivers to enhance at-home management. DATA SOURCE: A Medline search of
      the medical literature was used to identify articles that describe the burden,
      clinical presentation, and management of RGE. CONCLUSIONS: RGE is a serious
      medical condition characterized by diarrhea and vomiting and is a major cause of
      morbidity and hospitalization among children aged 5 years or younger. Proper at
      home treatment can be challenging; however, improved home care may limit
      emergency department visits and hospitalizations. IMPLICATIONS FOR PRACTICE: Mild
      to moderate RGE may be successfully managed at home if caregivers are adequately
      educated in deciding when a child needs to be evaluated in a physician's office
      and in managing dehydration at home.

PMID- 16958774
TI  - Graduate students' experiences with standardized patients as adjuncts for
      teaching pelvic examinations.
AB  - PURPOSE: To explore graduate nurse practitioner students' perceptions of their
      experiences when learning to perform pelvic examinations in the laboratory and
      performing them in subsequent clinical rotations. One group was taught by faculty
      with voluntary peer examination, and the other two groups were taught by
      standardized patients (SPs). DATA SOURCES: Surveys with open- and closed-ended
      (responses on Likert scales) items administered twice during 3 consecutive years
      to students enrolled in an advanced health assessment course. CONCLUSIONS: All
      groups reported feeling anxious while learning pelvic exam techniques and in
      subsequent clinical experiences. SPs provided immediate feedback to students,
      decreased their feelings of anxiety, and increased their confidence in performing
      examinations. Students who were taught pelvic examination techniques by SPs rated
      their learning experiences more positively and reported a better understanding of
      exam techniques than students who learned to perform exams by voluntary
      examination of classmates. IMPLICATIONS FOR PRACTICE: Graduate nursing programs
      should consider locating and using SP programs for teaching pelvic examinations
      in advanced health assessment courses. Although more cost-effective, voluntary
      peer examination was a less effective teaching method.

PMID- 16958775
TI  - Cost-effectiveness of nurse practitioner management of hypercholesterolemia
      following coronary revascularization.
AB  - PURPOSE: To evaluate the cost-effectiveness of case management by a nurse
      practitioner (NP) to lower blood lipids in patients with coronary heart disease
      (CHD) from a managed care perspective. DATA SOURCES: A total of 228 consecutive,
      eligible adults with hypercholesterolemia and CHD were recruited during
      hospitalization after coronary revascularization. Patients were randomized to
      receive lipid management, including individualized lifestyle modification and
      pharmacologic intervention from an NP for 1 year after discharge in addition to
      their usual care (NURS) or to receive usual care (EUC) enhanced with feedback on
      lipids to their primary provider and/or cardiologist. A cost-effectiveness ratio
      was calculated using incremental costs of the NURS group per unit change and
      percent change in low-density lipoprotein cholesterol (LDL-C) for 1 year at 2004
      values. CONCLUSIONS: The annual incremental cost-effectiveness of NP case
      management was 26.03 dollars per mg/dL and 39.05 dollars per percent reduction in
      LDL-C. When costs of NURS care for the second 6 months of management were
      compared to the first 6 months of management, nursing salary costs were lower as
      patients were established on cholesterol management regimens, but the reduction
      in costs was offset by the increase in incremental costs of drug treatment as the
      NP titrated the patient to higher drug dosages that were more costly.
      IMPLICATIONS FOR PRACTICE: The findings suggest that case management by an NP is
      a cost-effective approach for a managed care organization to consider in
      improving the care of patients with cardiovascular disease.

PMID- 16958776
TI  - Neurophysiological techniques to assess pain in animals.
AB  - Neurophysiological techniques are widely applied to animals, both in the search
      as a monitor for adequacy of anaesthesia, and studies to assess the efficacy of
      analgesic agents. Laboratory animals have been extensively used in models to
      investigate pain in man. However a substantial number of studies have also used
      neurophysiological techniques to increase knowledge of pain in specific animal
      species, with the aim of improving animal welfare. This review provides an
      overview of neurophysiological techniques involving the brain that have been used
      in the assessment of pain in animals. An explanation of the methodology of EEG
      recording, with particular emphasis on veterinary studies, is given.
      Neurophysiological models developed to assess pain in different species are
      described, and their relevance to advancements in animal welfare or best clinical
      practice indicated.

PMID- 16958777
TI  - Enrofloxacin and marbofloxacin in horses: comparison of pharmacokinetic
      parameters, use of urinary and metabolite data to estimate first-pass effect and
      absorbed fraction.
AB  - Enrofloxacin and marbofloxacin are two veterinary fluoroquinolones used to treat
      severe bacterial infections in horses. A repeated measures study has been
      designed to compare their pharmacokinetic parameters, to investigate their
      bioavailability and to estimate their absorbed fraction and first-pass effect by
      using plasma, urinary and metabolite data collected from five healthy mares.
      Clearance and V(d(ss)) were greater for enrofloxacin (mean +/- SD = 6.34 +/- 1.5
      mL/min/kg and 2.32 +/- 0.32 L/kg, respectively) than for marbofloxacin (4.62 +/-
      0.67 mL/min/kg and 1.6 +/- 0.25 L/kg, respectively). Variance of the AUC(0-inf)
      of marbofloxacin was lower than that for enrofloxacin, with, respectively, a CV =
      15% and 26% intravenously and a CV = 31% and 55% after oral administration. Mean
      oral bioavailability was not significantly different between marbofloxacin (59%)
      and enrofloxacin (55%). The mean percentage of the dose eliminated unchanged in
      urine was significantly higher for marbofloxacin (39.7%) than that for
      enrofloxacin (3.4%). Absorbed fraction and first-pass effect were only
      determinable for enrofloxacin, whereas the percentage of the dose absorbed in the
      portal circulation was estimated to be 78% and the fraction not extracted during
      the first pass through the liver was 65%. Consequently, the moderate observed
      bioavailability of enrofloxacin appears to be mainly caused by hepatic first-pass
      effect.

PMID- 16958778
TI  - Qualitative assessment of human exposure to consumption of injection site
      residues.
AB  - The recent adoption of the guideline on injection site residues in food producing
      animals by the Committee for Medicinal Products for Veterinary Use (CVMP) raised
      the question on the risk specifically related to injection site consumption. As
      noted in this guideline, residues at injection sites commonly deplete
      erratically. For the calculation of withdrawal time, treating residues at the
      injection site like those that occur in other tissues is questionable. An
      assessment of the risk related to the consumption of a whole or part of an
      injection site during a year was performed using a probabilistic approach. The
      risk assessment was modelled on the regimen of a 7-day antibiotic treatment, and
      was calculated on the scale of the European Union (EU) as a whole or of each
      European country. Our analysis indicated a maximal risk of 4 days of injection
      site consumption during a year in the EU. It also indicated that 37% of consumers
      would never eat an injection site in the same period. These results suggest that
      the risk of injection site consumption belongs more appropriately to an acute
      exposure risk than to a chronic one which is usually posed by the residues
      present in other edible tissues.

PMID- 16958779
TI  - Critical review on the withdrawal period calculation for injection site residues.
AB  - This review concerns a statistical method for calculating withdrawal period for
      injection site residues. A recently adopted Committee for Medicinal Products for
      Veterinary Use/European Agency for the Evaluation of Medicinal Product
      (CVMP/EMEA) guideline recommends to apply the same method for the calculation of
      withdrawal period for injection site residues as for other edible tissues. For
      reasons in this study developed below, this approach is deemed to be
      inappropriate for the injection site residues. The injection site residues often
      violate regression assumptions with regard to homoscedasticity (same variance in
      residue concentrations for different slaughter times) and linearity (of the mean
      depletion curve in log(e)-scale). The currently recommended method cannot
      adequately handle these aspects. An alternative pragmatic method taking into
      account the last slaughter time with all data below the reference threshold,
      combined with a safety span, is proposed for injection site residues. A
      nonparametric approach for calculating the withdrawal period is also presumed to
      be a sound alternative. The references commonly used are the Maximum Residue
      Limit (MRL) and the Acceptable Daily Intake (ADI). Unfortunately these references
      are not relevant to the acute risk exposure associated with injection site
      consumption. The use of alternative references, such as the Acceptable Single
      Dose Intake (ASDI) or the Acute Reference Dose (ARD) are thought to be more
      appropriate.

PMID- 16958780
TI  - Enrofloxacin assay validation and pharmacokinetics following a single oral dose
      in chickens.
AB  - The pharmacokinetics of enrofloxacin (ENRO), a fluoroquinolone antimicrobial
      agent, was studied in male broiler chickens (Cobb) after single oral
      administration of 10 mg of ENRO/kg b.w. A high-performance liquid chromatography
      photodiode array detector (DAD) (HPLC-DAD) method was developed and validated and
      used for quantitation of ENRO and its major metabolite ciprofloxacin in plasma.
      The HPLC analyses were carried out using a cationic-octadecyl mixed column and
      0.05 mol/L phosphate buffer (pH 2.5)/acetonitrile as mobile phase. The sample
      preparation of plasma consisted of the precipitation of proteins followed by
      solid phase extraction on cationic-octadecyl mixed cartridges. The method was
      validated considering linear range, linearity, selectivity, sensitivity, limit of
      detection (LOD), limit of quantitation (LOQ), intra- and inter-day precisions and
      accuracy. The LOD and LOQ for both fluoroquinolones were 60 and 200 ng/mL for
      plasma. The plasma concentration vs. time graph was characteristic of a two
      compartment open model. The maximal plasma concentration of 1.5 +/- 0.2 mg/mL was
      achieved at 9 +/- 2 h. The elimination half-life and the mean residence time of
      ENRO were 1.5 +/- 0.2 and 15.64 h, respectively. The area under the concentration
      time curve was calculated as 35 +/- 4 mgxh/mL.

PMID- 16958781
TI  - Effects of growth hormone and gonadotrophin releasing hormone antagonists on
      ovarian follicle growth in sheep.
AB  - Our objective was to determine the effects of the administration of growth
      hormone (GH) alone or plus teverelix, a gonadotrophin releasing hormone
      antagonist (GnRHa), on follicle development in sheep. Ewes were treated daily for
      6 days by the intramuscular route with 15 mg of GH alone (GH group; n = 6) or
      combined with two subcutaneous doses of GnRHa (1.5 mg) on days 0 and 3 of GH
      treatment (GH/GnRHa group; n = 6); the control group (n = 6) received similar
      treatment with saline solution. Plasma follicle stimulating hormone levels were
      significantly lower in the GH/GnRHa group than in the control (P < 0.001) and GH
      groups (P < 0.05). The number of follicles > or =2 mm increased to reach
      significant differences with control (18.7 +/- 0.6) on day 4 in GH/GnRHa group
      (22.7 +/- 0.5, P < 0.001) and on day 5 in GH group (20.3 +/- 0.4 vs. 17.0 +/-
      0.6, P < 0.05). These results indicate that GH and GnRHa may be useful for
      increasing the number of gonadotrophin-responsive follicles in the ovary.
      However, follicle function could be affected as both GH and GH/GnRHa groups
      showed lower plasma inhibin A concentrations than control sheep (90-110 pg/mL vs.
      170-185 pg/mL, P < 0.005).

PMID- 16958782
TI  - Mucosal permeability of water-soluble drugs in the equine jejunum: a preliminary
      investigation.
AB  - Ussing chambers have been used to study the mucosal permeability of drugs in
      humans, rats and other species. This data can then be used to develop in vitro/in
      vivo correlations (IVIVC) for drugs based on the Biopharmaceutics Classification
      System (BCS). Due to the poor oral bioavailability of many drugs in the horse,
      this method may be useful for screening drugs before development to determine if
      they warrant further study. Cephalexin (CPX), marbofloxacin (MAR), metronidazole
      (MTZ) and fluconazole (FCZ) were chosen for this study based on the wide range of
      physicochemical properties and bioavailability in the horse. Permeability was
      ranked as follows: MTZ > FCZ > MAR > CPX. This correlated with the
      bioavailability (R(2) = 0.633447), the Log P (R(2) = 0.648517), as well as the
      molecular weight (R(2) = 0.851208) of the drugs. Metronidazole induced a decrease
      in the tissue transepithelial resistance, suggestive of the possibility of tissue
      toxicity, which may have falsely increased its permeability. The low permeability
      of cephalexin across the tissue may indicate a lack of active transporters that
      are found in other species. From this study, we can conclude that the Ussing
      chamber is a promising method for determining mucosal permeability in the horse.

PMID- 16958783
TI  - Assessment of endothelium-dependent vasodilation in equine digital resistance
      vessels.
AB  - Haemodynamic disturbances leading to ischaemia and reperfusion injury of the
      digit are thought to be involved in the pathophysiology of acute equine
      laminitis. Identification of physiological regulators of blood flow through the
      equine digit is important in identifying factors, which may predispose animals to
      laminitis. A method was developed to assess endothelium-dependent responses of
      the isolated Krebs-perfused equine digit by co-administration of 5
      hydroxytryptamine (5-HT) with vasodilator agents, carbachol (CCh), bradykinin
      (BK) and substance P (SP). Bolus co-administration of CCh (0.02-2 micromol), BK
      and SP (0.02-0.2 nmol), caused inhibition of the 5-HT pressor response by 50-60%.
      The vasodilator responses were abolished by the detergent, CHAPS, indicating
      endothelium dependency; whereas vasoconstrictor responses to 5-HT were
      potentiated. CCh-induced relaxation was significantly reduced by the nitric oxide
      synthase inhibitor L-NAME (79.7 +/- 3.4% inhibition), whereas a large proportion
      of BK and SP-induced relaxation remained (34.1 +/- 6.3% and 33.6 +/- 5.3%
      inhibition). L-NAME potentiated vasoconstrictor responses to 5-HT. In conclusion,
      this study demonstrates that endothelium-derived NO modulates the response to
      vasoconstrictors such as 5-HT and is likely to be an important regulator of blood
      flow in the digital resistance vascular bed. Other factor(s) released by the
      endothelium are also important in regulating blood flow, whose identity remains
      to be established.

PMID- 16958784
TI  - Pharmacokinetics of enrofloxacin in Korean catfish (Silurus asotus).
AB  - The objective of this study was to evaluate the pharmacokinetic profile of
      enrofloxacin and its active metabolite, ciprofloxacin, in Korean catfish after
      intravenous and oral administrations. Enrofloxacin was administered to Korean
      catfish by a single intravenous and oral administrations at the dose of 10 mg/kg
      body weight. The plasma concentrations from intravenous and oral administrations
      of enrofloxacin were determined by LC/MS. Pharmacokinetic parameters from both
      routes were described to have a two-compartmental model. After intravenous and
      oral administrations of enrofloxacin, the elimination half-lives (t(1/2,beta)),
      area under the drug concentration-time curves (AUC), oral bioavailability (F)
      were 17.44 +/- 4.66 h and 34.13 +/- 11.50 h, 48.1 +/- 15.7 microgxh/mL and 27.3
      +/- 12.4 microgxh/mL, and 64.59 +/- 4.58% respectively. The 3.44 +/- 0.81 h
      maximum concentration (C(max)) of 1.2 +/- 0.2 microg/mL. Ciprofloxacin, an active
      metabolite of enrofloxacin, was detected at all the determined time-points from
      0.25 to 72 h, with the C(max) of 0.17 +/- 0.08 microg/mL for intravenous dose.
      After oral administration, ciprofloxacin was detected at all the time-points
      except 0.25 h, with the C(max) of 0.03 +/- 0.01 microg/mL at 6.67 +/- 2.31 h.
      Ciprofloxacin was eliminated with terminal half-life t(1/2,beta) of 52.08 +/-
      17.34 h for intravenous administration and 52.43 +/- 22.37 h for oral
      administration.

PMID- 16958785
TI  - Effect of ofloxacin on theophylline pharmacokinetics at clinical dosage in dogs.
AB  - We examined the effects of ofloxacin (OFX) and norfloxacin (NFX) on theophylline
      (TP) pharmacokinetics in dogs. OFX, as a noncompetitive and mechanism-based
      inhibitor, and NFX, as a noncompetitive inhibitor, were orally administered (5
      mg/kg) for a single dose or multiple doses (12 hourly for 3 days). TP (5 mg/kg,
      i.v) was injected at 2 h after the final dose of the fluoroquinolones (FQs). The
      same dose of TP was injected (i.v) 3 weeks before the start of FQs treatment for
      control. Multiple doses of OFX significantly reduced the total body clearance
      (Cl(B)) of TP from 0.117 to 0.085 L/h/kg, although a single dose did not change
      it. Neither a single dose nor multiple doses of NFX changed the TP
      pharmacokinetics. Plasma NFX concentrations increased after multiple doses. Those
      of OFX also increased but were still two orders of magnitude below the K(i) for
      noncompetitive inhibition of CYP1A in dogs. Time-dependent reduction in Cl(B) of
      TP suggests that mechanism-based inhibition of OFX was the major mode to decrease
      Cl(B) of TP. The mechanism-based inhibition may result in substantial inhibition
      of CYP1A activities in clinical conditions.

PMID- 16958786
TI  - The complete analysis of oxytetracycline pharmacokinetics in farmed Pacific white
      shrimp (Litopenaeus vannamei).
AB  - Lack of dosing information of the major antibiotics known as oxytetracycline
      (OTC) for the Pacific white shrimp (Litopenaeus vannamei) could have harmful
      impact on aquaculture in Thailand. The aim of this study was to detail complete
      pharmacokinetic information of OTC in the Pacific white shrimp. Sixty-four male
      L. vannamei weighing 14-22 g with carapace length of 2.30-3.00 cm in the
      standardized moulting stage of C-D(0) were used for the investigations. Single
      dose, 10 microg/g body weight OTC solution was administered intra-sinusally
      (i.s.), and the shrimps were then sampled in three replicates at time intervals
      of 0.25, 0.5, 2, 4, 6, 9, 12, 24, 48, 72, 170, 336 and 504 h postdose. OTC levels
      with time intervals in biological matrices including the hemolymph, abdominal
      muscle, and digestive gland of each sample were determined by validated high
      performance liquid chromatography, and were analyzed with noncompartment and
      compartment models. A simplified two-compartment model was employed rather than a
      more complicated model, with additional digestive compartment if necessary. A
      significant portion of the OTC was found in the digestive glands, even though the
      OTC was administered i.s. The model indicated that the OTC was thus not only
      distributed into the tissue compartment, but also to the digestive gland, from
      where it was eliminated from the shrimp's body. The dispositional half-lives of
      all compartments was found to be 14-21 h. Approximately 60% of the drug
      elimination took place in digestive gland, which is proposed to be the major
      route of elimination.

PMID- 16958787
TI  - Interspecies allometric scaling. Part I: prediction of clearance in large
      animals.
AB  - Interspecies scaling is a useful tool for the prediction of pharmacokinetic
      parameters from animals to humans, and it is often used for estimating a first
      time in human dose. The knowledge of pharmacokinetics in veterinary species is
      important for dosage selection, particularly in the treatment of large zoo animal
      species, such as elephants, giant cats and camels, for which pharmacokinetic data
      are scant. Therefore, the accuracy in clearance predictions in large animal
      species, with and without the use of correction factors (rule of exponents), and
      the impact of species selection in the prediction of clearance in large animal
      species was examined. Based upon this analysis, it was determined that there is a
      much larger risk of inaccuracies in the clearance estimates in large animal
      species when compared with that observed for humans. Unlike in humans, for large
      animal species, correction factors could not be applied because there was no
      trend between the exponents of simple allometry and the appropriate correction
      factor for improving our predictions. Nevertheless, we did see an indication that
      the exponents of simple allometry may alert us as to when the predicted clearance
      in the large animal may be underestimated or overpredicted. For example, if a
      large animal is included in the scaling, the predicted clearance in a large
      animal should be considered overestimated if the exponent of simple allometry is
      >1.3. Despite the potential for extrapolation error, the reality is that
      allometric scaling is needed across many veterinary practice situations, and
      therefore will be used. For this reason, it is important to consider mechanisms
      for reducing the risk of extrapolation errors that can seriously affect target
      animal safety, therapeutic response, or the accuracy of withdrawal time
      predictions.

PMID- 16958788
TI  - Interspecies allometric scaling: prediction of clearance in large animal species:
      part II: mathematical considerations.
AB  - Interspecies scaling is a useful tool for the prediction of pharmacokinetic
      parameters from animals to humans, and it is often used for estimating a first
      time in human dose. However, it is important to appreciate the mathematical
      underpinnings of this scaling procedure when using it to predict pharmacokinetic
      parameter values across animal species. When cautiously applied, allometry can be
      a tool for estimating clearance in veterinary species for the purpose of dosage
      selection. It is particularly valuable during the selection of dosages in large
      zoo animal species, such as elephants, large cats and camels, for which
      pharmacokinetic data are scant. In Part I, allometric predictions of clearance in
      large animal species were found to pose substantially greater risks of
      inaccuracies when compared with that observed for humans. In this report, we
      examine the factors influencing the accuracy of our clearance estimates from the
      perspective of the relationship between prediction error and such variables as
      the distribution of body weight values used in the regression analysis, the
      influence of a particular observation on the clearance estimate, and the
      'goodness of fit' (R(2)) of the regression line. Ultimately, these considerations
      are used to generate recommendations regarding the data to be included in the
      allometric prediction of clearance in large animal species.

PMID- 16958789
TI  - Pharmacokinetics of doxorubicinol in dogs.

PMID- 16958790
TI  - Pharmacokinetics of flunixin meglumine in swine after intravenous dosing.

PMID- 16958792
TI  - Weaning pig performance and faecal microbiota with and without in-feed addition
      of rare earth elements.
AB  - Two 6-week feeding trials were conducted on a total of 112 newly weaned piglets
      to examine the recently reported growth promoting effects of dietary rare earth
      elements (REE) in European pig production. Rare earth element-diets were
      supplemented with a REE-citrate premix of lanthanum and the light lanthanoides
      cerium, praseodymium and neodymium at 200 mg/kg for 6 weeks after weaning.
      Overall for both trials, growth performance of REE-citrate and control fed
      piglets did not differ significantly (p > 0.05). An early enhancive tendency for
      REE-citrate in trial 1 (feed conversion ratio, FCR -3%, p = 0.15) proved
      irreproducible in trial 2. In the late period of trial 1, in-feed addition of REE
      citrate significantly impaired piglet performance (FCR + 8%, p = 0.01). A
      cultivation-independent molecular approach, polymerase chain reaction-denaturing
      gradient gel electrophoresis was further applied to assess REE induced
      alterations in the predominant faecal microbiota from weaning pigs. Calculation
      of various ecological characteristics does not indicate (p > 0.05) an often
      discussed selective effect on local microbial composition of dietary REE.

PMID- 16958791
TI  - Hormonal disturbances associated with obesity in dogs.
AB  - Obesity is associated with multiple endocrine alterations and changes in the
      concentration of circulating hormones. However, few studies have explored such
      alterations in dogs with naturally acquired excess weight. In the present study,
      we investigated the effect of naturally acquired obesity on cortisol, insulin
      like growth factor (IGF)-1 and prolactin secretion in dogs. Thirty-one overweight
      dogs were enrolled in the trial. Blood samples were collected before and after
      adrenocorticotrophic hormone (ACTH) injection. Free thyroxine (fT4), cortisol,
      thyroid-stimulating hormone (TSH), IGF-1, prolactin and fructosamine were
      assayed. Body weight excess increased significantly with age and neutered dogs
      were more obese than entire ones. The ACTH stimulation test was within the normal
      range for 26 of 31 dogs. Prolactinaemia was increased in seven dogs and IGF-1 in
      six dogs. Twenty dogs had a fructosamine concentration >340 microm.
      Interestingly, 18 of 31 dogs showed disturbances of thyroid function based on
      high TSH and/or low fT4 baseline concentration, with 11 dogs showing both.
      According to these parameters only six of 31 dogs were free of hormonal
      disturbances. These results revealed the high incidence of such disturbances,
      especially thyroid dysfunction, in obese, but otherwise apparently healthy dogs.
      They demonstrate the importance of examining endocrine function during the
      initial evaluation of obese dogs to avoid failure of any nutritional treatment.

PMID- 16958793
TI  - Estimating the digestibility of Sahelian roughages from faecal crude protein
      concentration of cattle and small ruminants.
AB  - Studies on diet selection and feed intake of ruminants in extensive grazing
      systems often require the use of simple approaches to determine the organic
      matter digestibility (OMD) of the ingested feed. Therefore, we evaluated the
      validity of the one-factorial exponential regression established by Lukas et al.
      [Journal of Animal Science 83 (2005) 1332], which estimates OMD from the faecal
      crude protein (FCP) concentration. The equation was applied to two sets of data
      obtained with free grazing and pen-fed cattle, sheep and goats ingesting low and
      high amounts of green and dry vegetation of Sahelian pastures as well as millet
      leaves and cowpea hay. Data analysis showed that the livestock species did not
      influence the precision of estimation of OMD from FCP. For the linear regression
      between measured and estimated OMD (%) across n = 431 individual observations, a
      regression coefficient of r2 = 0.65 and a residual standard deviation (RSD) of
      5.87 were obtained. The precision of estimation was influenced by the data set (p
      = 0.033), the type of feed (p < 0.001) and the feeding level (p = 0.009), and
      interactions occurred between type of feed and feeding level (p = 0.021).
      Adjusting the intercept and the slope of the established exponential function to
      the present data resulted in a compression of the curve; while r2 remained
      unchanged, the RSD of the regression between measured and estimated OMD was
      reduced, when compared with the results obtained from the equation of Lukas et
      al. (2005). Estimating OMD from treatment means of FCP greatly improved the
      correlation between measured and estimated OMD for both the established function
      and the newly fit equation. However, if anti-nutritional dietary factors increase
      the concentration of faecal nitrogen from feed or endogenous origin, the approach
      might considerably overestimate diet digestibility.

PMID- 16958794
TI  - Effects of cadmium on serum sex hormone levels in pigs.
AB  - An inhibition of sex hormone secretion is observed in domestic animals exposed to
      cadmium in experimental conditions. Ninety-six gilts (Duroc x Landrace x
      Yorkshire, initial weight 27.59 kg) were randomly assigned into four different
      groups with three replications in each group (eight gilts per replication). The
      groups received the corn-soybean basal diet and supplemented with 0, 0.5, 5.0 and
      10.0 mg/kg cadmium (as CdCl2) respectively. The feeding trial was ended when body
      weight of pigs was approximately 90 kg. The results showed that 10.0 mg/kg
      cadmium significantly decreased average daily gain (p < 0.05) and increased
      feed/gain ratio (p < 0.05) of pigs. Follicle-stimulating hormone, luteinizing
      hormone, oestradiol (E2) and progesterone levels in serum of the pigs fed the
      diet supplemented with 10.0 mg/kg cadmium were lower significantly than those of
      the control (p < 0.05). Compared with the control, no changes were found in the
      levels mentioned above when the pigs fed the diet supplemented with 0.5 or 5.0
      mg/kg cadmium (p > 0.05). The changes of regulatory mechanism of the pituitary
      ovary axis may be the result of cadmium accumulation in pituitary and ovary and
      should be investigated further.

PMID- 16958795
TI  - Concentration of Ca, P, Mg, Na and K in muscle, fat and bone tissue of lambs of
      the breed German Merino Landsheep in the course of the growing period.
AB  - A growth experiment with 108 lambs (breed German Merino Landsheep) was carried
      out in order to examine how gender, body weight and feeding intensity affect
      major element concentrations in tissues and carcass. The lambs (50% male and 50%
      female) were fattened at three levels of feeding intensity ('high', 'medium' and
      'low' by varying daily amounts of concentrate and hay) and slaughtered at
      different final body weights (30, 45 or 55 kg). Six male and six female animals
      were killed at a final body weight of 18 kg representing the live weight at the
      beginning of the comparative slaughter experiment. The left half carcass of each
      animal was divided into muscle tissue, fat tissue and bones/sinews and analysed
      for the major elements calcium (Ca), phosphorus (P), magnesium (Mg), sodium (Na)
      and potassium (K). The major element concentrations of all tissues were
      significantly influenced by the body weight. An influence of gender could be
      noticed for all elements except Ca in the muscle and fat tissue. In the bone
      tissue, however, only the elements Na and K were influenced by gender. The
      feeding intensity had no significant effect on the concentration of major
      elements in the tissues. In lamb muscle tissue combined from all parts (body
      weight range 18-45 kg, both sexes) the following concentrations of major elements
      were analysed: 323 mg K, 185 mg P, 61.7 Na, 20.2 mg Mg and 10.6 mg Ca (per 100 g
      meat, wet weight basis). In conclusion, the genotype investigated shows on the
      whole concentrations of major elements which are close to values reported for
      lambs in the literature.

PMID- 16958797
TI  - Investigation on the growth of coprophagy-prevented rats with supplemented
      vitamin B12.
AB  - The growth of coprophagy-prevented rats was compared under administration of
      normal levels of vitamin B12 and supplemented amounts. Two experiments in which
      supplemented amounts of vitamin B12 were administered were conducted under
      different conditions. Six rats per group were fed under coprophagy-allowed
      (conventional feeding) and coprophagy-prevented conditions respectively. In the
      first experiment, coprophagy-prevented rats were fed only feed containing
      recommended vitamin B12 level and forced fed hydrous faeces, vitamin B12 and
      folic acid respectively. In the second experiment, coprophagy-prevented rats were
      fed AIN-93G at the recommended vitamin B12 level (25 microg/kg diet), at 100
      times the level and at 1000 times the level respectively. Body weight, feed
      consumption and amounts of each faeces type were determined in both experiments.
      In a comparison of body weight gain, we learned that coprophagy prevention
      reduced the values, but that there was no significant difference in the forced
      feeding group in the first experiment. Similar results were recognized in the
      second experiment. Vitamin B12 supplementation was not able to raise feed intake
      significantly and hence it obviously was not a severely limiting factor under the
      respective experimental condition which depressed feed intake.

PMID- 16958796
TI  - Calcium-excess causes subclinical changes of bone growth in Beagles but not in
      Foxhound-crossbred dogs, as measured in X-rays.
AB  - Numerous investigations and reports have covered the potential negative effects
      of an excess of calcium (Ca) in the skeletal development of young dogs. However,
      it still remains unclear why not all puppies, particularly of larger breeds,
      develop clinical signs of skeletal disorders after an overexposure to Ca. This
      trial with the small Beagle breed and a larger Foxhound-crossbred dog (with an
      adult weight of around 35 kg) investigated the effects of Ca-excess on parameters
      of bone growth. The employed small breed is known for its chondrodystrophic
      predispositions, no such data are reported for the slender hound-type Foxhound
      crossbred dogs. The Ca-supply had no influence on weight development and general
      health of the dogs. The measurements of bone lengths and widths in X-rays of the
      forearm of Beagles and Foxhound-crossbred dogs at 6 weeks of age, and again after
      a period of overexposure to Ca at about 27 weeks of age, revealed a growth
      reducing influence only in Beagles, without influence on clinical parameters of
      skeletal health.

PMID- 16958798
TI  - The relationships between leptin concentrations and body fat reserves in lambs
      are reduced by short-term fasting.
AB  - Feed deprivation decreases plasma leptin concentrations depending on the amount
      of body fat reserves. While a greater response was observed in lean than in fat
      humans and rats, a few results for ruminants are inconsistent. The objective of
      this study was to determine the influence of feed deprivation on plasma leptin
      concentration in growing lambs with different body fat reserves and on the
      relationship between leptin and fatness. In addition, we included other hormones
      (growth hormone, GH; insulin-like growth factor-I, IGF-I and insulin) involved in
      tissue development. Thirty male lambs of 40 kg live weight were used. Blood was
      sampled before and after a fasting period of 24 h. The lambs were slaughtered and
      dissected into several fat and lean tissues. Feed deprivation reduced plasma
      leptin by an average of 34.6% (p < 0.001). Obese lambs exhibited a greater
      decline of leptin than lean lambs (2.50 vs. 1.36 ng/ml, p < 0.05). The
      correlations between leptin and several fat tissues were lower in those lambs
      than that were fasted. This indicates that leptin concentrations after short-term
      fasting scarcely reflect the extent of body fat reserves but reflect more the
      actual metabolic situation. Body fat did not significantly influence the response
      of GH, IGF-I and insulin to fasting in most cases.

PMID- 16958799
TI  - Bee pollen product supplementation to horses in training seems to improve feed
      intake: A pilot study.
AB  - The objective of this study was to determine the efficacy of supplementation of
      Dynamic Trio 50/50, a bee pollen-based product, to improve physical fitness,
      blood leukocyte profiles, and nutritional variables in exercised horses. Ten
      Arabian horses underwent a standardised exercise test (SET), then were pair
      matched by sex and fitness and randomly assigned to BP (receiving 118 g of
      Dynamic Trio 50/50 daily) or CO (receiving 73 g of a placebo) for a period of 42
      days. A total collection was conducted from days 18 to 21 on six geldings to
      determine nutrient retention and neutral detergent fibre (NDF) and acid detergent
      fibre (ADF) digestibility. Horses were exercise conditioned and completed another
      SET on day 42. V160 and V200 were calculated from SET heart rates (HR). Lactate,
      glucose, haematocrit (HT) and haemoglobin (HB) concentrations were determined
      from SET blood samples. Total leukocyte count, and circulating numbers of various
      leukocytes and IgG, IgM and IgA concentrations were determined in rest and
      recovery blood samples from both SETs. Geldings on BP (n = 3) ate more feed than
      CO. BP had less phosphorus excretion, and tended to retain more nitrogen. BP
      tended to digest more NDF and ADF while having lower NDF digestibility and
      tending to have lower ADF digestibility. No treatment differences existed for
      V160 and V200, HR, lactate, HT and HB. There was a trend for lymphocyte counts to
      be lower in BP than CO on day 42. Dynamic Trio 50/50 supplementation may have a
      positive effect on performance by helping horses in training meet their
      potentially increased nutrient demands by increasing feed intake and thus
      nutrient retention.

PMID- 16958800
TI  - Subacute effects of moderate feed loads of isolated Fusarium toxin deoxynivalenol
      on selected parameters of metabolism in weaned growing piglets.
AB  - In 36 female weaned piglets, the effect of different dosages (0, 300, 600 and
      1200 microg/kg feed) of isolated, pure Fusarium toxin deoxynivalenol (DON) was
      examined during a period of 8 weeks. Standardised trial conditions were provided.
      Pigs were fed restrictively to allow a complete feed intake of all animals.
      Parameters of liver integrity, haematological data and blood concentrations of
      some selected metabolic components of energy and protein metabolism were examined
      weekly. Enzyme aspartate aminotransferase was affected subclinically by age and
      significantly by dosage, which was proved by Wald F-test. Some additional
      enzymes, for instance alanine aminotransferase, gamma glutamyl transferase,
      glutamate dehydrogenase and sorbit dehydrogenase, showed no clear systematic
      effect. Urea and glucose in the blood were inter-related. Depending on DON load
      with increasing glucose concentrations, the urea level declined. Albumin and
      total protein in serum showed no significant DON-related effect. Haemoglobin in
      blood was found to be significantly affected by DON, which was proved by the Wald
      F-test, where the effect was more pronounced with 600 microg DON/kg diet compared
      to 1 200 microg DON/kg. An obvious DON-related affection of liver, N-metabolism
      and stimulation of haematopoiesis depending on dosage and time is discussed.

PMID- 16958801
TI  - The influence of dietary conjugated linoleic acid on blood serum and colostrum
      immunoglobulin G concentration in female goats before and after parturition.
AB  - The effects on blood serum and colostrum immunoglobulin G (IgG) levels from
      including conjugated linoleic acid (CLA) in the diet were evaluated in goats. In
      experiment 1, 20 goats were allotted into two groups; the CLA group received 20
      g/kg of dry matter of CLA 60 and the control group received 0 g/kg of CLA 60,
      from the third month of gestation until partum. Blood samples were taken every 2
      weeks from 1 day before CLA inclusion to partum. From partum until 96 hours,
      blood and colostrum samples were taken every 24 h. Before partum, IgG serum blood
      levels were 15.6 and 9.4 mg/ml (CLA and control, respectively); the time effect
      was statistically significant. After partum (96 h), the effect of CLA dietary
      inclusion was statistically significant.

PMID- 16958802
TI  - Vibrio vulnificus infection and metalloprotease.
AB  - Vibrio vulnificus is ubiquitous in aquatic environments; however, it occasionally
      causes serious and often fatal infections in humans. These include invasive
      septicemia contracted through consumption of raw seafood, as well as wound
      infections acquired through contact with brackish or marine waters. In most cases
      of septicemia, the patients have underlying disease(s), such as liver dysfunction
      or alcoholic cirrhosis, and the secondary skin lesions including cellulitis,
      edema and hemorrhagic bulla appear on the limbs. Although V. Vul produces various
      virulent factors including polysaccharide capsule, type IV pili, hemolysin and
      proteolytic enzymes, the 45-kDa metalloprotease may be a causative factor of the
      skin lesions, because the purified protease enhances vascular permeability
      through generation of chemical mediators and also induces serious hemorrhagic
      damage through digestion of the vascular basement membrane. As well as other
      bacteria, V. Vul can regulate the protease production through the quorum-sensing
      system depending on bacterial cell density. However, this system operates
      efficiently at 25 degrees C, but not at 37 degrees C. Therefore, V. vulnificus
      may produce sufficient amounts of the protease only in the interstitial tissue of
      the limbs, in which temperature is lower than the internal temperature of the
      human body.

PMID- 16958803
TI  - Frequency of sister chromatid exchanges in the lymphocytes of patients with
      atopic dermatitis.
AB  - The combination of genetic susceptibility and environmental factors can induce
      allergic sensitization and subsequent local inflammation, resulting in atopic
      dermatitis (AD). Sister chromatid exchange (SCE) is a sensitive method that may
      reflect an instability in DNA or a deficiency in DNA repair. The aim of the
      present study was to investigate whether patients with AD have defects in DNA
      repair and whether SCE frequency can be used as a genetic marker in the
      pathogenesis of AD. Between September 2004 and July 2005, SCE was analyzed in the
      peripheral blood lymphocyte chromosomes of 32 patients with AD and 28 control
      subjects at the Dermatology Unit of Erzurum State Hospital. This study found that
      the SCE frequency was significantly increased in patients with AD (P < 0.00001).
      The prevalence of SCE was not correlated with patient age, sex, disease duration
      or AD disease severity. Our results indicate that increased chromosome
      instability may play an important role in the etiology of AD.

PMID- 16958804
TI  - Genetic analysis of the ferrochelatase gene in eight Japanese patients from seven
      families with erythropoietic protoporphyria.
AB  - A decrease in the activity of ferrochelatase (FECH; EC 4.99.1.1), the terminal
      enzyme of the heme biosynthetic pathway, results in erythropoietic protoporphyria
      (EPP; MIM 177000). We analyzed the FECHgene in eight Japanese EPP patients from
      seven non-consanguineous families and found two distinct genomic DNA
      abnormalities. In six patients from five families, there was a G-to-A point
      mutation at the first position of the intron 9 donor site; it resulted in
      aberrant splicing and skipping of exon 9 in FECH mRNA. In one patient, we found
      an A-to-G point-mutation 4 bases from the 3" terminus of intron 4 that led to the
      in-frame insertion of 3 bases in mRNA. No allelic anomalies, except for 3 single
      nucleotide polymorphisms were detected in another patient. We analyzed intron
      polymorphism at IVS3-48, known to be associated with the phenotypic expression of
      EPP, in these eight patients and 152 healthy Japanese volunteers. All patients
      were C/C homozygous for IVS3-48. The allelic frequency of IVS3-48C polymorphism
      in the healthy Japanese volunteers was 67.8% (103/152).

PMID- 16958805
TI  - Differential expression of matrix metalloproteinase-2 by fibroblasts in co
      cultures with keratinocytes, basal cell carcinoma and melanoma.
AB  - To address whether matrix metalloproteinase (MMP)-2 expression by mesenchymal
      fibroblasts may be differentially modulated by interactions with normal or
      malignant epidermal cells, we set up a fibroblast co-culture model separately
      with keratinocytes, basal cell carcinoma cells and melanoma cells. Real-time
      reverse transcription polymerase chain reaction (RT-PCR) and gelatin zymography
      were used to detect and quantify the expression of MMP-2 by these different kinds
      of cells. In independent cultures, MMP-2 was highly expressed by fibroblasts and
      melanoma cells constitutively, but barely expressed by keratinocytes and basal
      cell carcinoma (BCC) cells. MMP-2 expression by fibroblasts was downregulated in
      co-cultures with keratinocytes or BCC cells, but not with melanoma cells. These
      results indicate that epidermal-mesenchymal interactions are important modulators
      for MMP-2 expression by cutaneous cells and suggest a host-defense mechanism
      against the tumor progression of BCC.

PMID- 16958806
TI  - Chronic pulmonary complications associated with toxic epidermal necrolysis:
      report of a severe case with anti-Ro/SS-A and a review of the published work.
AB  - Patients with toxic epidermal necrolysis (TEN) have been known to have various
      complications. Though pulmonary complications are often observed, they usually
      show an acute form; however, chronic complications are quite rare and little is
      known about either their incidences or clinical manifestations. We herein report
      a 33-year-old man who presented with chronic pulmonary complications after a
      recovery from TEN. At the onset of TEN, he had severe respiratory failure and
      artificial ventilation was instituted. Despite being extubated successfully,
      respiratory failure reappeared 1 month later. A diagnosis of chronic bronchitis
      with severe obstructive ventilatory impairment and bronchiectasis was made and he
      was treated with steroids, bronchodilators and antibiotics, however, he died 1.5
      years after the onset of TEN. There have been 13 reported cases of chronic
      pulmonary complications with TEN or Stevens-Johnson syndrome (SJS) in the English
      published work. Such cases are usually classified into chronic
      bronchitis/bronchiolitis with obstructive change (including bronchiolitis
      obliterans and bronchiolitis obliterans organizing pneumonia), respiratory tract
      obstruction and bronchiectasis. Approximately 40% of all such patients die while
      the surviving continue to suffer from these complications because no curative
      therapy yet exists. As a result, the prognosis seems to be poor. The relationship
      between TEN and these chronic pulmonary complications remains to be elucidated.
      Interestingly, our patient was asymptomatically anti-Ro/SS-A positive at the
      onset of TEN. In addition, eccrine gland involvement and an extremely high level
      of serum salivary amylase were observed at the onset of TEN, furthermore, Sjogren
      like symptoms occurred after recovery from TEN. These findings suggested that the
      Sjogren-like autoimmune abnormalities induced by anti-Ro/SS-A correlated with the
      development of chronic pulmonary complications in our patient.

PMID- 16958807
TI  - Clinical trial of a laser device called fractional photothermolysis system for
      acne scars.
AB  - Ablative laser resurfacing is an effective treatment for acne scars. However,
      edema and prolonged erythema are common. Additionally, scarring and
      hyperpigmentation are often induced. A new concept of laser called fractional
      photothermolysis has been designed to create microscopic thermal wounds to
      achieve skin rejuvenation without significant side-effects. We treated 10
      patients with acne scars using this laser system (Reliant Fraxel SR Laser). All
      the patients were successfully treated with minimal adverse effects. The
      fractional photothermolysis system represents an optional method for the
      treatment of acne scars.

PMID- 16958808
TI  - Newborn infant with hemophagocytic lymphohistiocytosis and generalized skin
      eruptions.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a rare disease resulting from
      abnormal proliferation of histiocytes in tissues and organs. The incidence of HLH
      is 1:50,000-300,000. Cutaneous eruptions have been reported in 6-65% of the
      cases. It's important to differentiate the eruptions from other systemic
      diseases. We present an infant with prominent skin manifestations of HLH. On the
      11th day of life, she was admitted to our hospital with complaint of a
      generalized rash that had started the previous day. The eruptions consisted of
      irregularly shaped maculopapular erythematous rash and purpura. Bone marrow
      aspiration on the 25th day of life revealed hemophagocytosis with increased
      macrophages and histiocytes, consistent with HLH. Treatment was started with
      dexamethasone followed by induction chemotherapy with etoposide. All skin
      manifestations resolved in a few days. Although the clinical features are
      nonspecific, HLH should be kept in mind as an accompanying disease in neonates
      presenting with skin eruptions.

PMID- 16958809
TI  - Primary cutaneous aggressive epidermotropic CD8(+) cytotoxic T-cell lymphoma with
      atypical presentation.
AB  - Primary cutaneous aggressive epidermotropic CD8(+) cytotoxic T-cell lymphoma is
      characterized by a proliferation of epidermotropic CD8(+) cytotoxic T cells and
      an aggressive clinical behavior. Patients present with localized or disseminated
      eruptive papules, nodules and tumors. We report a case of primary cutaneous
      aggressive epidermotropic CD8(+) cytotoxic T-cell lymphoma with unusual clinical
      manifestation. The lesion occurred as multiple brownish macules and flat-topped
      papules on the hands, feet and face in a 25-year-old woman.

PMID- 16958810
TI  - Segmental neurofibromatosis: report of two cases.
AB  - Neurofibromatosis (NF), or von Recklinghausen's disease is comprised of a
      heterogeneous group of disorders, primarily affecting the skin, soft tissue, bone
      and central nervous system. Segmental neurofibromatosis (SN) is a rare form of
      NF, characterized by "cafe-au-lait" macules, freckles, and/or neurofibromas
      limited to a body segment. There are approximately 150 cases reported in the
      English published work. Bilateral segmental neurofibromatosis is a rare subtype
      of SN, manifesting with bilateral involvement of the body segments. Herein, we
      report two patients with SN; one associated with pectus excavatum, and the other
      case diagnosed as bilateral segmental neurofibromatosis. Asymmetry of the skull
      and thorax, kyphoscoliosis and segmental bone hypertrophy of the leg are skeletal
      abnormalities previously reported with SN. To the best of our knowledge, this is
      the first case of SN in association with pectus excavatum.

PMID- 16958811
TI  - Familial pigmented purpuric dermatoses.
AB  - Pigmented purpuric dermatoses (PPD) are chronic, asymptomatic dermatoses
      characterized by petechiae, pigmentation and rarely telangiectasias. Familial
      occurrence of PPD is very rare. We report four individuals in a family over three
      generations. The inheritance is suggestive of an autosomal dominant pattern.

PMID- 16958812
TI  - Successful treatment of granuloma annulare with topical 5-aminolaevulinic acid
      photodynamic therapy.

PMID- 16958813
TI  - Multiple giant pilomatricoma.

PMID- 16958814
TI  - Agminated lobular capillary hemangiomas presumably associated with an acquired
      arteriovenous malformation.

PMID- 16958815
TI  - Blue rubber bleb nevus syndrome with central nervous system involvement.

PMID- 16958816
TI  - Telangiectasias on the neck as a presenting cutaneous sign of Fabry disease.

PMID- 16958818
TI  - Interventions to improve adherence to medication in people with type 2 diabetes
      mellitus: a review of the literature on the role of pharmacists.
AB  - BACKGROUND AND OBJECTIVE: Pharmacists are now adopting a crucial role in the
      management of chronic illness in primary care, providing diabetes care and
      advice. This review aims to show whether a range of diabetes care interventions
      delivered by pharmacists is successful in improving adherence to medication.
      METHODS: The studies reviewed formed a subgroup of a Cochrane review on
      interventions to improve adherence to medication in people with type 2 diabetes.
      Search terms were 'type 2 diabetes mellitus' and 'compliance' or 'adherence'.
      Studies were included if they assessed adherence to medical treatment
      specifically, rather than other aspects of self-management. Out of the 21 studies
      selected for review, five described an intervention delivered by a pharmacist.
      RESULTS AND DISCUSSION: Two studies reported on attempts to improve adherence
      focused on the taking of medication. A system of reminders and packaging improved
      medication adherence, but measuring medicine taking through pill counts or
      Medication Event Monitoring System was not effective. Three studies evaluated
      pharmacist-led integrated management and education programmes designed to improve
      glycaemic control for under-served patient populations. They all succeeded in
      lowering glycated haemoglobin, but it remains unclear whether this resulted from
      improved patient adherence. CONCLUSION: This review indicates a potential benefit
      of pharmacist interventions to improve medication adherence in diabetes,
      especially in providing patient education.

PMID- 16958819
TI  - Effectiveness of raloxifene on bone mineral density and serum lipid levels in
      post-menopausal women with low BMD after discontinuation of hormone replacement
      therapy.
AB  - OBJECTIVE: To evaluate the effect of raloxifene on bone mineral density (BMD) and
      serum lipid levels in post-menopausal women who had discontinued hormone
      replacement therapy (HRT). METHODS: Thirty-four post-menopausal women with low
      BMD who had taken 60 mg of raloxifene daily for 12 months after discontinuing HRT
      were evaluated retrospectively. Information about their demographics, fracture
      history, BMD, lipid profiles and adverse events were collected from medical
      records and intranet database. The outcome measures were changes in the spine (L2
      L4) and femur BMD, serum lipid concentrations, fracture rate and tolerability.
      RESULTS: The post-menopausal women had a significant increase in their spine (L2
      L4) and femur BMD from their baseline BMD [spine, 2.9 +/- 4.6% (P < 0.001);
      femur, 3.0 +/- 6.6% (P = 0.01)]. Serum low-density lipoprotein (LDL) cholesterol
      was significantly reduced by 22.6% below baseline after 12 months (P = 0.007). No
      fractures were observed during therapy. Raloxifene was well tolerated. The most
      common adverse event was hot flash, which was generally mild. CONCLUSIONS:
      Raloxifene increases BMD at important skeletal sites, and lowers LDL cholesterol
      with tolerable adverse events.

PMID- 16958820
TI  - A retrospective study to determine the impact of medical- and lifestyle-based
      contraindications to a prescribed HAART regimen on clinical outcomes and
      adherence.
AB  - OBJECTIVE: To determine whether patients who are prescribed a highly active
      antiretroviral therapy regimen, that minimizes medical and lifestyle
      contraindications, will be better able to adhere to their drug regimens and will
      have better clinical outcomes, than patients who do not have such a regimen.
      METHODS: A retrospective chart review of patients' prescription renewals and
      changes in viral load and CD4(+) count and a comparison of these changes with
      patients' self-identified contraindications. Contraindications were identified by
      a questionnaire with 35 questions relating to medical history/concurrently
      prescribed medication and 16 questions on lifestyle. Main outcome measures are
      adherence assessed by prescription renewals, change in plasma HIV-1 RNA viral
      loads, and change in CD4(+) T-lymphocyte counts. Logistic and linear regression
      and student t-test were used to identify associations between outcome
      measurements and number of contraindications. RESULTS: A total of 203 patients
      (72% male, 74% African-American, 7% Hispanic) completed the questionnaire.
      Seventy-four per cent of the patients had at least one medical/drug
      contraindication and 78% had at least one lifestyle contraindication. Increases
      in CD4 counts were reduced by an average of 13 cells/mm(3) (P = 0.033) for each
      medical/drug contraindication and viral load decreases was significant even with
      one medical contraindication vs. none (P = 0.042). Patients with fewer lifestyle
      contraindications were more likely to have at least a 1 log drop in viral load (P
      = 0.036). For each increase in the number of contraindications, there was a
      corresponding 2% decrease in the rate of adherence (P = 0.048). CONCLUSIONS: The
      results suggest that using a patient administered questionnaire it is possible to
      identify contraindications in prescribed regimens that impact on adherence and on
      treatment effects on viral load and CD4 counts.

PMID- 16958821
TI  - 2'-,5'-Oligoadenylate synthetase response ratio predicting virological response
      to PEG-interferon-alpha2b plus ribavirin therapy in patients with chronic
      hepatitis C.
AB  - OBJECTIVE: Although all the mechanisms of elimination of hepatitis C virus (HCV)
      by Interferon (IFN) have not been fully elucidated, the 2'-5'-oligoadenylate (2
      5A) system is one of the mechanisms of the antiviral effect of IFN. Consequently,
      the measurement of 2'-5'-oligoadenylate synthetase (2-5AS) activity could be
      useful for the evaluation of IFN treatment. This retrospective study was aimed at
      assessing whether 2-5AS activity functions as a clinical marker of virological
      response to PEG-interferon-alpha2b (PEG-IFN) plus ribavirin therapy of chronic
      hepatitis C. METHODS: The 32 patients included in this study had high viral loads
      of serum HCV-RNA of genotype 1b with chronic hepatitis C. All the patients
      received a regimen of PEG-IFN plus ribavirin for 48 weeks, and were then divided
      into two groups: one group (effective group) with undetectable serum HCV-RNA
      levels at 24 weeks (n = 22) of therapy, the other group (ineffective group) with
      persistent presence of HCV-RNA in serum at 24 weeks (n = 10). The 2-5AS activity
      in serum was measured 2, 8 and 12 weeks before initial administration. RESULTS:
      The 2-5AS response ratio (measured value/measured value of baseline 2-5AS) at 2,
      8 and 12 weeks after the administration in the effective group was significantly
      higher than that in the ineffective group. CONCLUSIONS: These results suggest
      that the ratio of 2-5AS is closely related to the antiviral effect, and that the
      measurement of 2-5AS response ratio may be a useful clinical parameter of
      virological response to PEG-IFN plus ribavirin therapy of chronic hepatitis C.

PMID- 16958822
TI  - Population pharmacokinetic parameters of vancomycin in critically ill patients.
AB  - BACKGROUND: Intensive care unit patients are a highly heterogeneous population.
      Accurate dosing for this population requires characterization of the appropriate
      pharmacokinetic parameters. OBJECTIVE: To estimate population pharmacokinetic
      parameters of vancomycin (VAN) in adult critically ill patients and to establish
      the predictive performance of the resulting model. PATIENTS AND METHOD: Fifty
      critically ill patients with suspected or documented infection with VAN-sensitive
      micro-organisms were included. Thirty patients and 234 serum concentration-time
      sets obtained during clinical routine monitoring were used to estimate the
      pharmacokinetic parameters (group A). An open bicompartimental model with
      intermittent intravenous administration was used to adjust the data. Data were
      evaluated using a nonlinear mixed effects model (nonmem software). Forty plasma
      concentration-time data sets from 20 patients were used for validation using the
      Bayesian method (group B). RESULTS: There was a linear relationship between
      creatinine clearance (Cl(cr)) and VAN clearance (Cl(VAN)). The inclusion of the
      non-renal clearance (Cl(nr)) (intercept of Cl(VAN) vs. Cl(cr) relationship)
      improved the model significantly (Cl(nr) 17 mL/min). The volume of distribution
      seems to be larger than previously reported: volume of the central compartment
      (V(c)) was 0.41 L/kg and volume of the peripheral compartment was (V(p)), 1.32
      L/kg. The mean error (bias) and mean absolute error (precision) for predicting
      subsequent peak concentrations were -2.16 and 9.28 mg/L and for trough
      concentrations, -0.22 and 3.87 mg/L respectively. CONCLUSION: The use of
      population-specific pharmacokinetic parameters and Bayesian forecasting improves
      dosage-regimen design.

PMID- 16958823
TI  - Hospital-acquired venous thromboembolism and prophylaxis in an integrated
      hospital delivery system.
AB  - BACKGROUND: Without prophylaxis, hospital-acquired deep vein thrombosis (DVT) is
      approximately 10-40% among medical or general surgical patients and
      thromboprophylaxis for high-risk patients is currently recommended. This study
      analyse the risk factors associated with patients who developed a hospital
      acquired venous thromboembolism (VTE) and what prior prophylaxis, if any, were
      given to these patients. METHODS: We identified 1 year of secondary VTE from
      seven metropolitan hospitals. A random sample was selected and reviewed
      retrospectively. Data abstracted included age, gender, VTE risk factors,
      surgeries, VTE prophylaxis, and anticoagulant dosing. Data analysis consisted of
      descriptive statistics. RESULTS: A total of 118 patients with mean age 72.1 years
      (range 23-96) and 55.1% female. There were 60.2% DVT followed by 36.4% pulmonary
      embolism (PE); 7.6% had both DVT and PE diagnosed. About 73.7% of the study
      patients had two or more VTE risk factors. Five (4.2%) patients with hospital
      acquired VTE had no risk factors. Overall, 88.5% of patients with risk factors
      received adequate VTE prophylaxis; 20.3% received heparin or enoxaparin, 56.6%
      received warfarin, and 11.5% received mechanical prophylaxis secondary to drug
      contraindications. Nine (8.0%) patients with risk factors and no
      contraindications, did not received any prophylaxis while four patients (3.5%)
      received inadequate prophylaxis. All-cause mortality was 13.6% (16/118).
      CONCLUSION: Less than 5% of hospital-acquired VTE occurred in patients with no
      risk factors while 74% occurred in patients with two or more risk factors. In
      this seven-hospital study, 11.5% of hospital-acquired VTE with prior risk factors
      did not receive adequate prophylaxis. Educational in-services on the new CHEST
      guidelines should be provided within the hospitals to increase adherence to
      prophylaxis guidelines.

PMID- 16958824
TI  - Age-related changes in consultations and antibiotic prescribing for acute
      respiratory infections, 1995-2000. Data from the UK General Practice Research
      Database.
AB  - BACKGROUND: International studies using data aggregated for all ages have shown
      decreasing rates of general practice consultations for acute respiratory
      infections with fewer antibiotic prescriptions issued per consultation. The
      occurrence of different respiratory infections varies widely at different ages
      but we do not know whether prescribing has reduced equally in all age groups.
      OBJECTIVE: We aimed to determine how reductions in consultation rates and
      antibiotic prescribing varied with age for different respiratory infections.
      METHODS: Data were abstracted from the General Practice Research Database for 108
      general practices in the UK (mean registered population 642 685). We estimated
      age-specific changes between 1995 and 2000 in consultation rates, and the
      proportion of consultations resulting in an antibiotic prescription for 'all
      respiratory infections' and for 'sore throat', 'ear infection', 'bronchitis' and
      'chest infection'. RESULTS: Consultation rates for 'all respiratory infections'
      declined in all age groups with the greatest decreases in children aged 1-4 years
      (41%), 5-10 year olds (53%) and 11-16 year olds (54%), whereas at 75-84 years the
      reduction was 28%. The pattern of greater reductions in children held for each
      separate condition even though the age of peak incidence varied. The relative
      reduction in antibiotic prescribing was greatest at 1-4 years (18%), 5-10 years
      (17%) and 11-16 years (17%), compared with 5% at 75-84 years. Antibiotic
      prescribing decreased most for sore throat and this was observed at all ages
      particularly in 5-10 year olds (relative reduction, 32%). CONCLUSIONS: School age
      children account for the greatest reduction in consultations for acute
      respiratory infection. School age and preschool children account for the greatest
      reductions in antibiotic prescribing during the consultation. The rapid changes
      in consultation rates are unexplained.

PMID- 16958825
TI  - Pharmacokinetic and pharmacodynamic modelling of the effects of glimepiride on
      insulin secretion and glucose lowering in healthy humans.
AB  - Glimepiride is an oral sulfonylurea antihyperglycaemic agent. We used
      pharmacokinetic-pharmacodynamic (PK-PD) modelling to analyse the relationship
      between plasma glimepiride concentration, insulin secretion and glucose lowering
      to determine the effects of the drug in healthy volunteers. A single 2-mg oral
      dose of glimepiride was administered to six healthy volunteers. The control group
      received a placebo. All subjects consumed 12 g of sugar immediately after drug
      administration in order to standardize the initial plasma glucose levels. Serial
      blood sampling was performed for 9 h after oral dosing. Plasma glimepiride,
      insulin and glucose levels were determined by validated methods (LC/MS/MS assay,
      hexokinase method and radioimmunoassay respectively). Time courses of plasma
      glimepiride concentration, insulin secretion, and glucose lowering effects were
      analysed by means of PK-PD modelling with the ADAPT II program. The time course
      of the plasma concentrations followed a two-compartmental model with a lag time.
      The glimepiride concentration peaked at 191.5 ng/mL at approximately 4 h after
      administration. The maximal increase in insulin secretion was 9.98 mIU/L and the
      maximal decrease in plasma glucose was 19.33 mg/dL. Both peak effects occurred at
      approximately 2.5 h after drug intake. The glucose disappearance model was used
      to analyse glimepiride's insulin secretion and glucose lowering effects. The PK
      PD model described well the relationship between plasma glimepiride and its
      insulin secretion and hypoglycaemic effects in healthy volunteers.

PMID- 16958826
TI  - A six-year evaluation of methadone prescribing practices at a substance misuse
      treatment centre in the UK.
AB  - OBJECTIVES: To document changes in prescribing practice at a specialized
      substance misuse service in the UK occurring since the introduction of the 1999
      UK National Guidelines on the management of drug misuse, and to explore a
      possible link between the length of time spent in methadone maintenance therapy
      (MMT) and the dosage prescribed. METHODS: A retrospective analysis of a
      computerized prescription database between 1996 and 2002 obtained from Sheffield
      Care Trust Substance Misuse Service was performed. The relationship between
      various measures of dosage and the length of time spent in MMT was investigated.
      RESULTS: In accordance with the 1999 UK National Guidelines, the proportion of
      injectable methadone prescribed decreased from 22% to 16%. This was offset by an
      increase in the prescribing of methadone elixir from 74% to 79%. The 'maximum
      dose' of methadone prescribed correlated significantly with patient retention,
      explaining 14% of the variation in time spent in MMT. CONCLUSIONS: Our findings
      indicate that publication of the UK National Guidelines had a measurable effect
      on prescribing practice at the Service. We found that a higher methadone dose is
      associated with increased patient retention in MMT. However, as only a maximum of
      14% of the variation in the length of stay is related to methadone dose, the
      importance of other aspects of treatment such as counselling and rehabilitation
      programmes, should be considered for the successful treatment of opioid abusers.

PMID- 16958827
TI  - Medication management at home: medication risk factor prevalence and inter
      relationships.
AB  - BACKGROUND AND OBJECTIVE: Patients can have medication-related risk factors
      associated with poor health outcomes that become evident through visiting them in
      their homes. These medication-related risk factors may not be apparent in
      pharmacy and general practitioner (GP) records. The aim was to determine the
      prevalence and inter-relationships of medication-related risk factors for poor
      patient health outcomes identifiable through 'in-home' observations. METHODS: The
      design was a cross-sectional study of 204 general practice patients living in
      their own homes and at risk of medication-related poor health outcomes.
      Medication-related risk factors were identified in the patients' homes by
      community pharmacists and GPs. RESULTS AND DISCUSSION: The prevalence of risk
      factors varied from 8.3% (multiple medication storage locations) to 55.9%
      (confused by generic and trade names). There were many relationships observed
      between the medication-related risk factors, with expired medication having the
      most relationships with other risk factors followed by therapeutic duplication
      and poor adherence (9, 6 and 6 relationships respectively). CONCLUSION: Visiting
      patients' homes may identify medication-related risk factors not otherwise
      apparent through patient visits to the health practitioner when medications may
      be brought for review (i.e. 'brown bag' reviews).

PMID- 16958828
TI  - CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine.
AB  - BACKGROUND: Venlafaxine (V) is a mixed serotonin and noradrenaline reuptake
      inhibitor used as a first-line treatment of depressive disorders. It is
      metabolized primarily by the highly polymorphic cytochrome P450 (CYP) enzyme
      CYP2D6 to yield a pharmacologically active metabolite, O-desmethylvenlafaxine
      (ODV), and to a lesser extent by CYP3A4, to yield N-desmethylvenlafaxine (NDV).
      OBJECTIVES: The aim of this study was to assess whether the O-demethylation
      phenotype of V has an impact on the pharmacokinetics and clinical outcome.
      METHOD: In 100 patients treated with V, serum concentrations of V, ODV and NDV
      and the ratios of concentrations ODV/V as a measure of O-demethylation were
      determined. Individuals exhibiting abnormally high or low metabolic ratios of
      ODV/V were selected for genotyping. Clinical effects were monitored by the
      Clinical Global Impressions Scale and side effects by the UKU (Udvalg for
      Kliniske Undersogelser Side Effect Rating Scale) rating scale. RESULTS: There was
      wide inter-individual variability in ODV/V ratios. The median ratio ODV/V was 1.8
      and the 10th and 90th percentiles 0.3 and 5.2, respectively. Individuals with
      ODV/V ratios below 0.3 were all identified as poor metabolizers (PM), with the
      genotypes *6/*4 (n = 1), *5/*4 (n = 2) or *6/*6 (n = 1). Individuals with ratios
      above 5.2 were all ultra rapid metabolizers (UM, n = 6) due to gene duplications.
      Five individuals with intermediate metabolic activity (ODV/V, 1.1 +/- 0.8) were
      heterozygotes with the CYP2D6*4 genotype, and one patient with an intermediate
      metabolic ratio of 4.8 had the genotype *4/2x*1. Clinical outcome measurements
      revealed that patients with ODV/V ratios below 0.3 had more side effects (P <
      0.005) and reduced serum concentrations of sodium (P < 0.05) in comparison with
      other patients. Gastrointestinal side effects, notably nausea, vomiting and
      diarrhoea were the most common. Differences in therapeutic efficacy were not
      significant between the different phenotypes. CONCLUSION: The O-demethylation
      phenotype of V depends strongly on the CYP2D6 genotype. A PM phenotype of CYP2D6
      increases the risk of side effects.

PMID- 16958829
TI  - Cost comparison of epoetin alpha, epoetin beta and darbepoetin alpha for cancer
      patients with anaemia in the clinical practice setting.
AB  - BACKGROUND AND OBJECTIVE: Cost control is becoming an increasingly important
      consideration for clinicians when planning how to provide the best treatment for
      anaemic cancer patients. Administration of erythropoiesis stimulating agents
      (epoetin alpha, epoetin beta and darbepoetin alpha) has become the standard of
      care for treatment of anaemia in cancer patients. However, only limited
      information is available on the economic comparability of epoetin alpha, epoetin
      beta and darbepoetin alpha, and thus this study was conducted to compare cost per
      patient of each of these agents for anaemic cancer patients. METHODS: All
      prescriptions of the agents over 1 year were analysed by two Austrian regional
      public health insurance associations and cost per patient for each agent was
      calculated from invoicing data. Data from the two regions were combined to obtain
      total mean drug costs per patient per year. RESULTS AND DISCUSSION: Analyses
      showed significantly lower costs for epoetin alpha ( 2,743.27 euros) than for
      darbepoetin alpha (3,627.98 euros ) or epoetin beta ( 3,292.28 euros): epoetin
      alpha vs. darbepoetin alpha (P < 0.0001); epoetin beta vs. darbepoetin alpha (P =
      0.0001); epoetin alpha vs. epoetin beta (P = 0.0009). As costs of the three
      agents in Austria are identical for therapeutically equivalent doses, the higher
      cost of darbepoetin alpha was believed to be due mainly to longer treatment
      duration to target haemoglobin level. CONCLUSION: The finding of a cost
      difference favouring epoetin alpha over darbepoetin alpha suggests the need for
      prospective randomized studies comparing efficacy and cost effectiveness of all
      three agents to obtain more definitive data.

PMID- 16958830
TI  - Enoxaparin-induced alopecia in patients with cerebral venous thrombosis.
AB  - OBJECTIVE: To report three cases of alopecia induced by the anticoagulant
      enoxaparin in cerebral venous thrombosis (CVT) patients. CASE SUMMARY: Three
      female patients were treated initially with direct intrasinus urokinase, and then
      followed by low-molecular-weight heparin (LMWH) enoxaparin at 1 mg/kg given
      subcutaneously twice daily for 3 weeks. It was switched to oral anticoagulant
      warfarin at 5 mg daily for another 6 months. Nearly 3 weeks after the initiation
      of anticoagulation, all of the three patients complained of excessive hair loss
      with large areas of patchy, non-scarring alopecia. Hair growth returned to normal
      within 1 month after the completion of enoxaparin. DISCUSSION: Unfractionated
      heparin remains the first-line treatment of CVT because of its efficacy, safety
      and feasibility. Alopecia has been reported as a side effect of LMWHs dalteparin
      and tinzaparin. The pattern of hair loss, telogen effluvium, involves the
      induction of the hair follicle into a resting phase without apparent pathologic
      implication. In addition, this article also reviewed other medications taken by
      the patients that are possibly associated with hair loss. CONCLUSION: From the
      review of literature, there is no report of alopecia caused by urokinase. Using
      the Naranjo ADR Probability Scale, a score of 6 suggests that enoxaparin was the
      probable cause of alopecia in our three patients. This report introduces evidence
      of alopecia as a probable side effect of enoxaparin, but stresses the efficacy
      and safety of LMWH. As this is not a life-threatening disorder, we hope to
      increase the awareness of pharmacists and clinicians to this relatively rare but
      important side effect.

PMID- 16958831
TI  - Cord blood transplantation for adults.
AB  - Allogeneic haematopoietic stem cell transplant has become an import tool for the
      treatment of high risk and advanced haematological diseases. However, allogeneic
      transplantation has been limited by the availability of suitable related and
      unrelated donors. The positive results with umbilical cord blood as an
      alternative source of haematopoietic stem cells for transplantation in the
      paediatric setting encouraged studies in adult patients. In adults, however, the
      progress of cord blood transplantation has been slower, in part limited by the
      limitation of cell dose. We review here the current state of the art on cord
      blood transplantation for adults, and discuss some of the newer strategies being
      pursued in order to improve its safety and efficacy.

PMID- 16958832
TI  - The blood centre as a community health resource.
AB  - Blood centres in the USA encounter over 35,000 blood donors every day, a number
      that is far exceeded worldwide. This daily encounter of thousands of people with
      the healthcare system offers an unusual opportunity for blood centres to engage
      these donors in ways that contribute to individual and community health. In
      addition, a positive interaction at the blood centre may encourage donors to
      return more often, thus enhancing the blood supply. The wealth of medical
      information gathered by blood centres also presents an opportunity for
      epidemiological studies of health and illness that affect the community at large.
      Donors receive a 'mini-physical' as part of the donor qualification process.
      Required procedures include blood pressure measurement and haemoglobin
      determination. Targeted education, counselling and referral of donors with
      hypertension and/or low haemoglobin engages them in the care of critical personal
      health issues. Carbonyl iron supplied to female donors of child-bearing age
      replaces iron lost in the donation and can retain them as active blood donors. A
      range of optional screening tests and procedures offer enhanced interactions
      between the donor and the blood centre. Inexpensive tests, such as cholesterol
      and random blood glucose determination, can detect abnormalities that may
      initiate further medical interventions to address cardiovascular and diabetic
      risks. These enhanced medical interactions with donors must be undertaken with
      care and appropriate medical supervision. However, the opportunity, indeed the
      responsibility, to act on important medical information enhances the range of
      medical support for donors and is an opening for blood centres to expand their
      involvement in the health of the community.

PMID- 16958833
TI  - Evidence-based decision making in transfusion medicine.
AB  - Some of the basic principles behind evidence-based medicine have been known for
      many years; however, the concept and approach to integrating evidenced-based
      decision making into clinical practice on a day-to-day basis has only evolved
      over the past 15 years. This paper focuses on five important steps in evidence
      based decision making: (1) the importance of a well-defined question; (2) ways to
      effectively search the scientific literature; (3) the process of critical
      appraisal for an article about therapy; (4) the role of clinical expertise,
      patient values, clinical circumstances and society's expectations in the decision
      making process; and (5) continuous quality improvement of the process.

PMID- 16958834
TI  - Creutzfeldt-Jakob disease and blood transfusion: results of the UK Transfusion
      Medicine Epidemiological Review study.
AB  - BACKGROUND AND OBJECTIVES: This paper reports the results to 1 March 2006 of an
      ongoing UK study, the Transfusion Medicine Epidemiological Review (TMER), by the
      National CJD Surveillance Unit (NCJDSU) and the UK Blood Services (UKBS) to
      determine whether there is any evidence that Creutzfeldt-Jakob disease (CJD),
      including sporadic CJD (sCJD), familial CJD (fCJD), and variant CJD (vCJD) is
      transmissible via blood transfusion. MATERIALS AND METHODS: Sporadic CJD and fCJD
      cases with a history of blood donation or transfusion are notified to UKBS. All
      vCJD cases aged > 17 years are notified to UKBS on diagnosis. A search for
      donation records is instigated and the fate of all donations is identified by
      lookback. For cases with a history of blood transfusion, hospital and UKBS
      records are searched to identify blood donors. Details of identified recipients
      and donors are checked against the NCJDSU register to establish if there are any
      matches. RESULTS: CJD cases with donation history: 18/31 vCJD, 3/93 sCJD, and 3/5
      fCJD cases reported as blood donors were confirmed to have donated labile
      components transfused to 66, 20, and 11 recipients respectively. Two vCJD
      recipients have appeared on the NCJDSU register as confirmed and probable vCJD
      cases. The latter developed symptoms of vCJD 6.5 years and 7.8 years respectively
      after receiving non-leucodepleted red blood cells (RBCs) from two different
      donors who developed clinical symptoms approximately 40 and 21 months after
      donating. A third recipient, given RBC donated by a further vCJD case
      approximately 18 months before onset of clinical symptoms, had abnormal prion
      protein in lymphoid tissue at post-mortem (5-years post-transfusion) but had no
      clinical symptoms of vCJD. CJD cases with history of transfusion: Hospital
      records for 7/11 vCJD and 7/52 sCJD cases included a history of transfusion of
      labile blood components donated by 125 and 24 donors respectively. Two recipients
      who developed vCJD were linked to donors who had already appeared on the NCJDSU
      register as vCJD cases (see above). No further links were established.
      CONCLUSION: This study has identified three instances of probable transfusion
      transmission of vCJD infection, including two confirmed clinical cases and one
      pre- or sub-clinical infection. This study has not provided evidence, to date, of
      transmission of sCJD or fCJD by blood transfusion, but data on these forms of
      diseases are limited.

PMID- 16958835
TI  - Detection of HTLV-I and -II in Scottish blood donor samples and archive
      donations.
AB  - BACKGROUND AND OBJECTIVES: Positive samples identified during routine serological
      screening for HCV (hepatitis C virus), HBV (hepatitis B virus) and HIV (human
      immunodeficiency virus) are confirmed by nucleic acid testing in the SNBTS
      (Scottish National Blood Transfusion Service) PCR Reference laboratory.
      Serological screening for HTLV-I (human T-cell lymphotropic virus type I) and -II
      was implemented in Scotland in November 2002, at which time a PCR assay was not
      available for confirmation. Our aim was to develop a real-time PCR assay that
      could be used for the confirmation of samples showing HTLV-I serological positive
      or indeterminate reactivity and to investigate whether a serologically silent
      carrier status exists ('Tax' only) in the Scottish donor population. MATERIALS
      AND METHODS: A real-time HTLV PCR was devised using a lymphoblastoid cell line
      which has HTLV-I sequence integrated in the genome (C8166 cells). These were
      spiked into peripheral blood mononuclear cells. The assay was evaluated on
      archived serologically confirmed HTLV-positive samples and new positives
      identified since implementation of screening. RESULTS: HTLV-I and -II were
      detected in cells and plasma from stored donations and a serological positive
      donation identified in routine screening. HTLV DNA can also be amplified from the
      plasma obtained from plasma preparation tubes. There was no evidence of a carrier
      status ('Tax' only) in 100 serologically negative blood donors tested. The PCR
      assay developed is reliable and sensitive, capable of identifying one copy of
      HTLV-I. CONCLUSIONS: The HTLV PCR is a useful addition for HTLV confirmation,
      especially in serologically indeterminate samples and for look-back studies. HTLV
      PCR confirmation will provide additional useful information for donor medical
      staff for counselling donors.

PMID- 16958836
TI  - Anti-HBc screening of blood donors: a comparison of nine anti-HBc tests.
AB  - BACKGROUND AND OBJECTIVES: Since voluntary introduction of hepatitis B virus
      (HBV) minipool nucleic acid amplification technology (NAT) at the German Red
      Cross, the expected residual risk of a transfusion-associated HBV infection has
      been estimated to be 1 : 500,000 - about 10 times higher than for human
      immunodeficiency virus (HIV) or hepatitis C virus (HCV) infection. Donors
      demonstrating chronic positivity for antibody to hepatitis B core antigen (anti
      HBc), negativity for hepatitis B surface antigen (HBsAg) and polymerase chain
      reaction (PCR)-negative with a low virus load are a major cause of this increased
      risk. MATERIALS AND METHODS: Ten-thousand blood donors from our blood-donation
      centre were screened for anti-HBc using the current PRISM HBc and the new PRISM
      HBcore assay to evaluate the diagnostic sensitivity and specificity of these
      tests. PRISM HBc- or PRISM HBcore-reactive samples were further analysed using
      seven additional tests for anti-HBc, two tests for antibody to hepatitis B
      surface antigen (anti-HBs), one test for antibody to hepatitis B envelope antigen
      (anti-HBe) and three HBV NAT assays. RESULTS: From a total of 10,000 donors, nine
      and 14 samples were reactive only in the PRISM HBc and the PRISM HBcore,
      respectively, whereas 165 samples were reactive in both anti-HBc assays. Further
      analysis of these 188 anti-HBc-reactive specimens in a total of nine different
      anti-HBc assays revealed concordant results for 162 (86.2%) specimens. Sample cut
      off values for anti-HBc were significantly (P < 0.01) lower for anti-HBc-only
      reactive samples compared with specimens that were also reactive for anti-HBs or
      anti-HBe. CONCLUSIONS: Both PRISM anti-HBc assays revealed that approximately
      1.8% of non-prescreened blood donors from Germany were reactive for anti-HBc.
      Although sensitivity was comparable between both assays, specificity was
      increased significantly with the PRISM HBcore. High anti-HBc sample cut-off
      values were indicative for reactivity in other HBV parameters and for concordant
      results in the nine different anti-HBc assays. Look-back investigations are
      necessary to estimate the infection risk both of anti-HBc-only positive and of
      anti-HBc/anti-HBs-positive blood transfusions.

PMID- 16958837
TI  - Prolonged storage of red blood cells affects aminophospholipid translocase
      activity.
AB  - BACKGROUND AND OBJECTIVES: Loss of phospholipid asymmetry in the membrane of red
      blood cells (RBC) results in exposure of phosphatidylserine (PS) and to
      subsequent removal from the circulation. In this study, we investigated the
      effect of long-term storage of RBCs on two activities affecting phospholipid
      asymmetry: the ATP-dependent aminophospholipid translocase (or flippase,
      transporting PS from the outer to the inner leaflet) and phospholipid scrambling
      (which will move PS from the inner to the outer leaflet). MATERIALS AND METHODS:
      Standard leukodepleted RBC concentrates were stored in saline-adenine-glucose
      mannitol (SAGM) at 4 degrees C for up to 7 weeks. PS exposure was determined by
      measurement of AnnexinV-FITC binding to the cells, flippase activity by
      measurement of the inward translocation of NBD-labelled PS. Scrambling activity
      was determined by following the inward translocation of fluorescent NBD
      phosphatidylcholine. In parallel, intracellular ATP levels were determined.
      RESULTS: PS exposure amounted to only 1.5 +/- 0.3% positive cells (n = 8) after 5
      weeks of storage, which slightly increased to 3.5 +/- 0.7% (n = 8) after 7 weeks
      of storage. Flippase activity started to decrease after 21 days of storage and
      reached 81 +/- 5% of the control value after 5 weeks of storage (n = 6) and 59 +/
      6% (n = 6) after 7 weeks. Also in RBC obtained by apheresis, flippase activity
      decreased upon storage. Scrambling activity remained virtually absent during
      storage, explaining the low PS exposure despite the decrease in flippase
      activity. Rejuvenation of RBC after 7 weeks to increase ATP levels only partially
      restored flippase activity, but in combination with a correction of the
      intracellular pH to that of fresh cells, almost complete restoration was
      achieved. The decrease in flippase activity after prolonged storage did make the
      RBCs more prone to PS exposure after activation of phospholipid scrambling.
      CONCLUSION: This study shows that, although PS exposure remains low, prolonged
      storage does compromise the RBC membrane by affecting flippase activity. When the
      metabolic changes induced by storage are corrected, flippase activity can be
      restored.

PMID- 16958838
TI  - The contribution of platelets in the production of cryoprecipitates for use in a
      fibrin glue.
AB  - BACKGROUND AND OBJECTIVES: Cryoprecipitate has a wide application for use as a
      fibrin glue. In some situations, platelets are added to the preparation in order
      to enhance the fibrin glue. MATERIALS AND METHODS: Fresh plasma was collected by
      apheresis from the same donor to produce 250 ml of platelet-rich plasma (PRP) or
      platelet-poor plasma (PPP) (n = 12 each). Cryoprecipitate was then produced
      following the standards of the American Association of Blood Banks and
      resuspended to a total volume of 8 ml, from which aliquots were removed and
      assayed. Clot formation was measured using the thromboelastogram. RESULTS: The
      protein content of the two preparations was identical for PRP and PPP. Results
      for fibrinogen (PPP 475 +/- 220 mg; PRP 399 +/- 215 mg), Factor VIII (PPP 186 +/-
      67 IU; PRP 175 +/- 70 IU) and von Willebrand Factor (PPP 260 +/- 104 IU; PRP 221
      +/- 88 IU) were not significantly different. The concentration of platelet
      derived growth factor was markedly higher (a 100-fold increase at 3778 +/- 1036
      ng) when platelets were added to the plasma. There was a small, but not
      statistically significant, difference in the rate of clot formation (R = 2.3 for
      PPP and 3.8 for PRP) and clot strength (MA = 63.4 for PPP and 56.6 for PRP)
      between PPP and PRP cryoprecipitates when measured using the thromboelastogram.
      CONCLUSIONS: Platelets do not significantly increase the concentration of the
      usual constituents of cryoprecipitate; however, the levels of platelet-derived
      growth factor are markedly enhanced. Therefore, there are advantages for using
      PRP to enhance the growth of new tissue.

PMID- 16958839
TI  - Fc function of a new intravenous immunoglobulin product: IGIV 10% triple virally
      inactivated solution.
AB  - BACKGROUND AND OBJECTIVES: Baxter AG has developed a new liquid intravenous
      immunoglobulin product [Immune Globulin Intravenous (IGIV) 10%] using a new
      manufacturing procedure. A modified Cohn fractionation and ion exchange
      chromatography is used to produce an IgG solution with no alterations to the Fc
      region. Three dedicated virus reduction steps are included: solvent-detergent
      treatment, nanofiltration, and incubation at low pH and elevated temperature in
      final formulation. We applied the reference method of the European Pharmacopoeia
      (EP) together with a flow-cytometric binding assay for the evaluation of the Fc
      function of the new product. MATERIALS AND METHODS: The EP reference method was
      done as described in the EP. The flow-cytometric method measured binding of IgG
      to Fc receptors of human monocytic THP-1 cells after exclusion of apoptotic
      cells. RESULTS: Sixteen lots of the new product expressed Fc functions between
      84% and 110% when analysed with the EP reference method and Fc-binding activities
      between 82% and 121% when determined by the flow-cytometric method. CONCLUSION:
      All tested lots of the new product demonstrated a high level of Fc activity and
      met the requirements of the EP for Fc function.

PMID- 16958840
TI  - Use of a (proposed) standard protocol to validate Terumo TSCD-II connections
      between dissimilar blood bag tubing.
AB  - BACKGROUND AND OBJECTIVES: ISO standards for blood bags do not adequately define
      and control the dimensions of blood bag transfer tubing. This lack of
      standardization presents potential difficulties when making sterile connections
      between the wide range of tubing that has evolved in the absence of such
      standards. We aim to validate the suitability of the TSCD-II and provide a
      minimum standard for assessing the suitability of sterile connections (welds)
      between dissimilar tubing. MATERIALS AND METHODS: The Terumo TSCD-II was used in
      this study to connect by hermetic welding seven tubing types with a wide range of
      dimensions from five suppliers. Thirty sterile connections were made between each
      combination split between dry/dry, wet/wet and dry/wet connections. Welds were
      assessed for visual defects, by tensile stress test (TST) and pressure tests.
      RESULTS: All welds passed visual inspection and pressure tests. All welds had a
      minimum tensile strength of greater than 40 N and mean of greater than 45 N.
      CONCLUSION: Successful connections have been made between dissimilar tube types
      and this work does not support the requirement for 'tight' tubing dimensional
      specifications. We have recommended to the ISO Technical Committee 76 Work Group
      1 that ISO 3826-1 be revised and should include a minimum standard validation
      protocol for joining dissimilar tubing.

PMID- 16958841
TI  - Transfusion audit of fresh-frozen plasma in southern Taiwan.
AB  - BACKGROUND AND OBJECTIVES: The demand for transfusions has increased rapidly in
      southern Taiwan. Between 1993 and 2003, requests for fresh-frozen plasma (FFP) in
      particular rose dramatically at Kaohsiung Medical University Hospital (KMUH).
      Transfusion orders were not tightly regulated, and inappropriate use of blood
      products was common. MATERIALS AND METHODS: We carried out a prospective analysis
      of transfusion requests from October 2003 to January 2004 at KMUH, and then
      repeated the audit for another 3-month period after the clinical faculty had
      undergone five sessions of education on transfusion guidelines. Later, our
      consultant haematologist applied computerized guidelines to periodic audits.
      RESULTS: A 5.2% decrease in inappropriate FFP usage followed the educational
      programme and a further 30% reduction took place after the application of
      computerized transfusion guidelines. With the guidelines and periodic audits, FFP
      transfusions decreased by 74.6% and inappropriate requests from 65.2% to 30%.
      CONCLUSIONS: Hospital policy, computerized transfusion guidelines and periodic
      audits greatly reduced inappropriate FFP transfusions. An educational campaign
      had a more limited effect.

PMID- 16958842
TI  - An evaluation of automated blood collection mixers.
AB  - BACKGROUND AND OBJECTIVES: We investigated the mixing capacity of two whole blood
      (WB) collection mixers. MATERIALS AND METHODS: WB was simulated by using a 25%
      glycerol solution warmed to 35 degrees C. Citrate-phosphate-dextrose (CPD)
      anticoagulant of a collection system was stained with toluidine blue, and
      simulated WB was added at 30, 60 or 90 ml/min, respectively (n = 3 per flow
      speed). The optical density (OD) of 10-ml fractions was measured, and results are
      expressed as percentage of a well-mixed '100%-sample'. RESULTS: CompoGuard showed
      adequate mixing at all three flow speeds (average ODs 96-103%). HemoLight showed
      good mixing at 60 and 90 ml/min (ODs from 97 to 101%). At 30 ml/min, mixing
      appeared suboptimal, but still conformed to our requirements with ODs from 96% to
      104%. CONCLUSION: Both mixers give sufficient mixing of whole blood with
      anticoagulant.

PMID- 16958843
TI  - Response to the international forum on haemovigilance.

PMID- 16958844
TI  - Developing insect models for the study of current and emerging human pathogens.
AB  - The study of human diseases requires the testing of microorganisms in model
      systems. Although mammals are typically used, we argue the validity of using
      insects as models in order to examine human diseases, particularly the growing
      number of opportunistic microorganisms. Insects can be used in large numbers, are
      easily manipulated, and are not subject to the same ethical concerns as mammalian
      systems. Insects and mammals have many parallels with respect to microbial
      pathogenesis, from proteinaceous integuments that require breaching before
      infection to similarities in their innate immune responses. Reactions of insects
      to Candida and Pseudomonas spp. infections show good correlation with mouse
      models, providing precedent-setting examples of the study of human pathogens
      using insects. Insects as pathogen hosts also warrant study because they may act
      as reservoirs for emerging human pathogens. Finally, insect models may be used to
      examine the evolutionary processes involved in the acquisition of virulence
      factors and host-jumping mechanisms indispensable to emerging pathogens. Insect
      models may be used in 'niche' investigations where large sample sizes can
      facilitate rapid, informative screening of opportunistic diseases and provide
      insights into pathogen evolution, while reducing the cost and ethical concerns
      associated with mammalian models.

PMID- 16958845
TI  - Weapons of mass destruction: virulence factors of the global killer
      enterotoxigenic Escherichia coli.
AB  - Enterotoxigenic Escherichia coli (ETEC) is the most common cause of food and
      water-borne E. coli-mediated human diarrhoea worldwide. The incidence in
      developing countries is estimated at 650 million cases per year, resulting in 800
      000 deaths, primarily in children under the age of five. ETEC is also the most
      common cause of diarrhoea among travellers, including the military, from
      industrialized nations to less developed countries. In addition, ETEC is a major
      pathogen of animals, being responsible for scours in cattle and neonatal and
      postweaning diarrhoea in pigs and resulting in significant financial losses.
      Studies on the pathogenesis of ETEC infections have concentrated on the plasmid
      encoded heat-stable and heat-labile enterotoxins and on the plasmid-encoded
      antigenically variable colonization factors. Relatively little work has been
      carried out on chromosomally encoded virulence factors. Here, we review the known
      virulence factors of ETEC and highlight the future for combating this major
      disease.

PMID- 16958846
TI  - Ubiquity and diversity of multidrug resistance genes in Lactococcus lactis
      strains isolated between 1936 and 1995.
AB  - The presence and the nucleotide sequence of four multidrug resistance genes,
      lmrA, lmrP, lmrC, and lmrD, were investigated in 13 strains of Lactococcus lactis
      ssp. lactis, four strains of Lactococcus lactis ssp. cremoris, two strains of
      Lactococcus plantarum, and two strains of Lactococcus raffinolactis. Multidrug
      resistance genes were present in all L. lactis isolates tested. However, none of
      them could be detected in the strains belonging to the species L. raffinolactis
      and L. plantarum, suggesting a different set of multidrug resistance genes in
      these species. The analysis of the four deduced amino acid sequences established
      two different variants depending on the subspecies of L. lactis. Either lmrA, or
      lmrP, or both were found naturally disrupted in five strains, while full-length
      lmrD was present in all strains.

PMID- 16958847
TI  - Microarray expression profiling of Yersinia pestis in response to
      chloramphenicol.
AB  - Plague is a deadly disease caused by Yersinia pestis. Human plague can be
      effectively controlled by timely antibiotic administration, chloramphenicol being
      a drug of choice. In this study, a DNA microarray was used to investigate the
      gene expression profile of Y. pestis in response to chloramphenicol. Seven
      hundred and fifty-five genes were differentially expressed on chloramphenicol
      treatment: 364 genes were up-regulated and 391 were down-regulated. In addition
      to a large number of genes encoding unknown or unassigned functions, genes
      encoding the components of the translation apparatus, cell envelope and
      transport/binding functions were strongly represented amongst the induced genes.
      Genes encoding proteins involved in energy metabolism and synthesis and
      modification of macromolecules were strongly represented amongst the down
      regulated genes. A number of heat-shock genes were also repressed. These global
      transcriptional changes provide an insight into the mechanisms of action of
      chloramphenicol against Y. pestis.

PMID- 16958848
TI  - Identification and characterization of EspK, a type III secreted effector protein
      of enterohaemorrhagic Escherichia coli O157:H7.
AB  - Enterohaemorrhagic Escherichia coli (EHEC) causes bloody diarrhoea in humans and
      deploys a type III secretion system (T3SS) encoded by the locus of enterocyte
      effacement to elicit the formation of attaching and effacing (AE) lesions on
      intestinal epithelia. Here, we report the identification of a new secreted
      substrate of this system, z1829, which is encoded by cryptic prophage CP-933N.
      Elevated secretion of a beta-lactamase-z1829 fusion protein was detected upon
      mutation of sepD in EHEC O157:H7 and the fusion protein was translocated into
      infected epithelial cells in a T3SS-dependent manner; accordingly, we named the
      protein EspK. In common with the related Salmonella enterica type III secreted
      effector GogB, we observed that EspK localized to the cytoplasm when transiently
      expressed in COS-7 cells using EspK-specific antiserum. Inactivation of espK did
      not impair adherence or actin nucleation during infection of HeLa cells but
      affected persistence of EHEC O157:H7 in the intestines of orally inoculated
      calves. Inactivation of an orthologue of espK in the murine AE pathogen
      Citrobacter rodentium did not impair intestinal colonization in mice.

PMID- 16958849
TI  - Directed evolution of an artificial bifunctional enzyme, gamma-glutamyl
      kinase/gamma-glutamyl phosphate reductase, for improved osmotic tolerance of
      Escherichia coli transformants.
AB  - To produce the artificial bifunctional enzyme gamma-glutamyl kinase/gamma
      glutamyl phosphate reductase, a mutant library of the proBA fusion gene from
      Bacillus subtilis was created by error-prone PCR. Selecting by functional
      complementation of the proline auxotroph Escherichia coli JM83 and NaCl
      tolerance, we isolated a mutant of the proBA fusion gene that improved the
      osmotolerance of host cells of E. coli JM83. A single amino acid replacement
      (Asn177Asp) located in a conserved domain in gamma-glutamyl kinase leads to
      overproduction of proline by host cells. The mutated gamma-glutamyl kinase/gamma
      glutamyl phosphate reductase enzyme was rendered about 100-fold less sensitive to
      proline-mediated feedback inhibition than the control.

PMID- 16958850
TI  - New genus-specific primers for the PCR identification of novel isolates of the
      genus Streptomonospora.
AB  - The halophilic actinomycete genus Streptomonospora, forming a distinct branch in
      the 16S rRNA gene phylogenetic tree adjacent to the genera Nocardiopsis and
      Thermobifida, was first proposed by Cui et al. to accommodate the species type
      Streptomonospora salina. During a biodiversity and taxonomic study on halophilic
      filamentous actinomycetes from a saline lake in western China, numerous new
      halophilic actinomycetes strains were isolated. To confirm whether they are
      members of the genus Streptomonospora, one set of genus-specific oligonucleotides
      was designed which allows rapid detection of members of the genus
      Streptomonospora by means of PCR amplification. The genus specificity of these
      primers was validated with reference strains as well as with wild-type isolates,
      which exhibited morphological characteristics common to this genus.

PMID- 16958851
TI  - The sigma factor RpoN (sigma54) is involved in osmotolerance in Listeria
      monocytogenes.
AB  - Listeria monocytogenes is able to grow under conditions of high osmolarity. We
      constructed a deletion mutant of rpoN, encoding the alternative sigma factor
      RpoN, and analyzed its response to osmotic stress. In a minimal medium with 4%
      NaCl and 1 mM betaine, the mutant showed a similar growth to that of the parental
      strain, EGD. In the same medium with 4% NaCl and 1 M carnitine, the growth rate
      of the mutant was greatly reduced, when the optical density at 600 nm (OD600) at
      the starting point of growth, was 0.15. However, when growth of the culture was
      started at an OD600 of 0.025, the growth of the mutant was similar to that of
      EGD. The mutant's expression of two betaine transporter genes, betL and gbuB, and
      the carnitine transporter gene opuCA, was osmotically induced at a level similar
      to EGD, and its rate of carnitine uptake was similar to that of EGD. These
      results suggest that the growth defect from the rpoN mutant is caused not by the
      transcriptional regulation of opuCA or by a decrease in carnitine uptake, but
      possibly by larger amounts of carnitine being needed for growth of the mutant in
      minimal medium when NaCl is present.

PMID- 16958852
TI  - Role of penicillin-binding protein 1b in competitive stationary-phase survival of
      Escherichia coli.
AB  - The penicillin-binding proteins (PBPs) catalyze the synthesis and modification of
      bacterial cell wall peptidoglycan. Although the biochemical activities of these
      proteins have been determined in Escherichia coli, the physiological roles of
      many PBPs remain enigmatic. Previous studies have cast doubt on the individual
      importance of the majority of PBPs during log phase growth. We show here that
      PBP1b is vital for competitive survival of E. coli during extended stationary
      phase, but the other nine PBPs studied are dispensable. Loss of PBP1b leads to
      the stationary phase-specific competition defective phenotype and causes cells to
      become more sensitive to osmotic stress. Additionally, we present evidence that
      this protein, as well as AmpC, may assist in cellular resistance to beta-lactam
      antibiotics.

PMID- 16958853
TI  - Microbial community structure in soils with decomposing residues from plants with
      genetic modifications to lignin biosynthesis.
AB  - Lignin is a major determinant of the decomposition of plant materials in soils.
      Advances in transgenic technology have led to the possibility of modifying lignin
      to improve the pulping properties of plant materials for papermaking. Previous
      studies have shown that lignin modifications also affect the rate of plant
      material decay in soil. The aim of this work was to investigate short-term
      changes in soil microbial community structures when tobacco residues with reduced
      activity of enzymes in the monolignol pathway decompose. The residues from lignin
      modified plants all decomposed faster than unmodified plant materials. The
      relative proportions of some of the structural groups of microbial phospholipid
      fatty acids were affected by genetic modifications, especially the proportion of
      double unsaturated chain fatty acids, indicative of fungi.

PMID- 16958854
TI  - Functional effects of intramembranous proline substitutions in the staphylococcal
      multidrug transporter QacA.
AB  - The QacA multidrug transporter is encoded on Staphylococcus aureus multidrug
      resistance plasmids and confers broad-range antimicrobial resistance to more than
      30 monovalent and bivalent lipophilic, cationic compounds from at least 12
      different chemical classes. QacA contains 10 proline residues predicted to be
      within transmembrane regions, several of which are conserved in related export
      proteins. Proline residues are classically known as helix-breakers and are highly
      represented within the transmembrane helices of membrane transport proteins,
      where they can mediate the formation of structures essential for protein
      stability and transport function. The importance of these 10 intramembranous
      proline residues for QacA-mediated transport function was determined by examining
      the functional effect of substituting these residues with glycine, alanine or
      serine. Several proline-substituted QacA mutants failed to confer high-level
      resistance to selected QacA substrates. However, no single proline mutation,
      including those at conserved positions, significantly disrupted QacA protein
      expression or QacA-mediated resistance to all representative substrates,
      suggesting that these residues are not essential for the formation of structures
      requisite to the QacA substrate transport mechanism.

PMID- 16958855
TI  - Effects of an invasive cattail species (Typha x glauca) on sediment nitrogen and
      microbial community composition in a freshwater wetland.
AB  - Sediments from Cheboygan Marsh, a coastal freshwater wetland on Lake Huron that
      has been invaded by an emergent exotic plant, Typhaxglauca, were examined to
      assess the effects of invasion on wetland nutrient levels and sediment microbial
      communities. Comparison of invaded and uninvaded zones of the marsh indicated
      that the invaded zone showed significantly lower plant diversity, as well as
      significantly higher aboveground plant biomass and soil organic matter. The
      sediments in the invaded zone also showed dramatically higher concentrations of
      soluble nutrients, including greater than 10-fold higher soluble ammonium,
      nitrate, and phosphate, which suggests that Typhaxglauca invasion may be
      impacting the wetland's ability to remove nutrients. Terminal restriction
      fragment length polymorphism analyses revealed significant differences in the
      composition of total bacterial communities (based on 16S-rRNA genes) and
      denitrifier communities (based on nirS genes) between invaded and uninvaded
      zones. This shift in denitrifiers in the sediments may be ecologically
      significant due to the critical role that denitrifying bacteria play in removal
      of nitrogen by wetlands.

PMID- 16958856
TI  - The arbuscular mycorrhizal fungal protein glomalin is a putative homolog of heat
      shock protein 60.
AB  - Work on glomalin-related soil protein produced by arbuscular mycorrhizal (AM)
      fungi (AMF) has been limited because of the unknown identity of the protein. A
      protein band cross-reactive with the glomalin-specific antibody MAb32B11 from the
      AM fungus Glomus intraradices was partially sequenced using tandem liquid
      chromatography-mass spectrometry. A 17 amino acid sequence showing similarity to
      heat shock protein 60 (hsp 60) was obtained. Based on degenerate PCR, a full
      length cDNA of 1773 bp length encoding the hsp 60 gene was isolated from a G.
      intraradices cDNA library. The ORF was predicted to encode a protein of 590 amino
      acids. The protein sequence had three N-terminal glycosylation sites and a string
      of GGM motifs at the C-terminal end. The GiHsp 60 ORF had three introns of 67, 76
      and 131 bp length. The GiHsp 60 was expressed using an in vitro translation
      system, and the protein was purified using the 6xHis-tag system. A dot-blot assay
      on the purified protein showed that it was highly cross-reactive with the
      glomalin-specific antibody MAb32B11. The present work provides the first evidence
      for the identity of the glomalin protein in the model AMF G. intraradices, thus
      facilitating further characterization of this protein, which is of great interest
      in soil ecology.

PMID- 16958857
TI  - Identification of a Francisella tularensis LVS outer membrane protein that
      confers adherence to A549 human lung cells.
AB  - Francisella tularensis is a highly pathogenic bacterium; however, little is known
      about its initial interactions with mucosal surfaces of the human respiratory
      tract. To investigate these interactions, we tested whether two Francisella
      strains could adhere to A549 human lung epithelial cells. We found that LVS
      adhered well to these cells while Francisella novicida adhered poorly. We used
      surface biotinylation to identify bacterial proteins that might mediate this
      adherence. We report the identification of the F. tularensis surface protein
      FsaP, which, when expressed in nonadherent Escherichia coli, confers recombinant
      bacteria with the ability to bind to A549 cells.

PMID- 16958858
TI  - Meningococcal adhesion suppresses proapoptotic gene expression and promotes
      expression of genes supporting early embryonic and cytoprotective signaling of
      human endothelial cells.
AB  - Neisseria meningitidis colonizes the human nasopharynx and occasionally causes
      lethal or damaging septicemia and meningitis. Here, we examined the adherence
      mediated signaling of meningococci to human cells by comparing gene expression
      profiles of human umbilical vein endothelial cells (HUVEC) infected by adherent
      wild-type, frpC-deficient mutant, or the nonadherent (DeltapilD) N. meningitidis.
      Pili-mediated adhesion of meningococci resulted in alterations of expression
      levels of human genes known to regulate apoptosis, cell proliferation,
      inflammatory response, adhesion and genes for signaling pathway proteins such as
      TGF-beta/Smad, Wnt/beta-catenin and Notch/Jagged. This reveals that adhering
      piliated meningocci manipulate host signaling pathways controlling cell
      proliferation while establishing a commensal relationship.

PMID- 16958859
TI  - Correlation between bacterial indicators and bacteriophages in sewage and sludge.
AB  - The use of bacteriophages as potential indicators of faecal pollution has
      recently been studied. The correlation of the number of bacterial indicators and
      the presence of three groups of bacteriophages, namely somatic coliphages
      (SOMCPH), F-RNA-specific phages (FRNAPH) and phages of Bacteroides fragilis
      (BFRPH), in raw and treated wastewater and sludge is presented in this study. Raw
      and treated wastewater and sewage sludge samples from two wastewater treatment
      plants in Athens were collected on a monthly basis, over a 2-year period, and
      analysed for total coliforms, Escherichia coli, intestinal enterococci and the
      three groups of bacteriophages. A clear correlation between the number of
      bacterial indicators and the presence of bacteriophages was observed. SOMCPH may
      be used as additional indicators, because of their high densities and resistance
      to various treatment steps.

PMID- 16958861
TI  - Accounting for uncertainty in marine reserve design.
AB  - Ecosystems and the species and communities within them are highly complex systems
      that defy predictions with any degree of certainty. Managing and conserving these
      systems in the face of uncertainty remains a daunting challenge, particularly
      with respect to developing networks of marine reserves. Here we review several
      modelling frameworks that explicitly acknowledge and incorporate uncertainty, and
      then use these methods to evaluate reserve spacing rules given increasing levels
      of uncertainty about larval dispersal distances. Our approach finds similar
      spacing rules as have been proposed elsewhere - roughly 20-200 km - but
      highlights several advantages provided by uncertainty modelling over more
      traditional approaches to developing these estimates. In particular, we argue
      that uncertainty modelling can allow for (1) an evaluation of the risk associated
      with any decision based on the assumed uncertainty; (2) a method for quantifying
      the costs and benefits of reducing uncertainty; and (3) a useful tool for
      communicating to stakeholders the challenges in managing highly uncertain
      systems. We also argue that incorporating rather than avoiding uncertainty will
      increase the chances of successfully achieving conservation and management goals.

PMID- 16958864
TI  - Non-neutral patterns of species abundance in grassland communities.
AB  - Although the distribution of plant species abundance in a Minnesota grassland was
      consistent with neutral theory, niche but not neutral mechanisms were supported
      by the ability of species traits to predict species abundances in three
      experimental grassland communities. In particular, data from 27 species grown in
      monoculture showed that species differed in a trait, R*, which is the level to
      which each species reduced the concentration of soil nitrate, the limiting soil
      nutrient and which is predicted to be inversely associated with competitive
      ability for nitrogen (N). In these N-limited habitats, species abundance ranks
      correlated with their predicted competitive ranks: low R* species, on average
      dominated. These correlations were significantly different than expected for
      neutral theory, which assumes the exchangeability of species traits.
      Additionally, we found that changes in relative abundance after environmental
      change (N-addition or disturbance) were not neutral but also were significantly
      associated with R*.

PMID- 16958865
TI  - Additive and interactive effects of plant genotypic diversity on arthropod
      communities and plant fitness.
AB  - Recent research suggests that genetic diversity in plant populations can shape
      the diversity and abundance of consumer communities. We tested this hypothesis in
      a field experiment by manipulating patches of Evening Primrose (Oenothera
      biennis) to contain one, four or eight plant genotypes. We then surveyed 92
      species of naturally colonizing arthropods. Genetically diverse plant patches had
      18% more arthropod species, and a greater abundance of omnivorous and predacious
      arthropods, but not herbivores, compared with monocultures. The effects of
      genotypic diversity on arthropod communities were due to a combination of
      interactive and additive effects among genotypes within genetically diverse
      patches. Greater genetic diversity also led to a selective feedback, as mean
      genotype fitness was 27% higher in diverse patches than in monocultures. A
      comparison between our results and the literature reveals that genetic diversity
      and species diversity can have similar qualitative and quantitative effects on
      arthropod communities. Our findings also illustrate the benefit of preserving
      genetic variation to conserve species diversity and interactions within
      multitrophic communities.

PMID- 16958866
TI  - Seasonal, El Nino and longer term changes in flower and seed production in a
      moist tropical forest.
AB  - It has recently been reported that humid tropical forests are changing rapidly in
      response to global anthropogenic change and that these forests experience greater
      tree mortality and even fire during droughts associated with El Nino events. The
      former reports are controversial largely because a single method has been used -
      repeated censuses of tree plots. The latter reports focus on recent extreme El
      Nino events. Here, we show that flower and seed production both increase during
      El Nino events in an old-growth tropical forest in Panama. Flower production, but
      not seed production, has also increased over the past 18 years. The sustained
      increase in flower production was greater for 33 liana species than for 48 tree
      species. These results indicate that moderate El Nino events favour seed
      production, document long-term increases in flower production for the first time,
      and corroborate long-term increases in the importance of lianas using independent
      methods. Changes in levels of solar irradiance might contribute to all three
      patterns.

PMID- 16958867
TI  - Scale-dependent interactions and community structure on cobble beaches.
AB  - Recent theory suggests that scale-dependent interaction between facilitation and
      competition can generate spatial structure in ecological communities. The
      application of this hypothesis, however, has been limited to systems with little
      underlying heterogeneity. We evaluated this prediction in a plant community along
      an intertidal stress gradient on cobble beaches in Rhode Island, USA. Prior
      studies have shown that Spartina alterniflora facilitates a forb-dominated
      community higher in the intertidal by modifying the shoreline environment. We
      tested the hypothesis that, at a smaller scale, Spartina competitively excludes
      forb species, explaining their marked absence within the lower Spartina zone.
      Transplant experiments showed forb species grow significantly better in the
      Spartina zone when neighbours were removed. Removal of the Spartina canopy led to
      a massive emergence of annual forbs, showing that competition limits local
      occupation. These findings indicate that interaction of large-scale facilitation
      and small-scale competition drives plant zonation on cobble beaches. This study
      is the first to provide empirical evidence of scale-dependent interactions
      between facilitation and competition spatially structuring communities in
      heterogeneous environments.

PMID- 16958868
TI  - Quantifying the extinction vortex.
AB  - We developed a database of 10 wild vertebrate populations whose declines to
      extinction were monitored over at least 12 years. We quantitatively characterized
      the final declines of these well-monitored populations and tested key theoretical
      predictions about the process of extinction, obtaining two primary results.
      First, we found evidence of logarithmic scaling of time-to-extinction as a
      function of population size for each of the 10 populations. Second, two lines of
      evidence suggested that these extinction-bound populations collectively exhibited
      dynamics akin to those theoretically proposed to occur in extinction vortices.
      Specifically, retrospective analyses suggested that a population size of n
      individuals within a decade of extinction was somehow less valuable to
      persistence than the same population size was earlier. Likewise, both year-to
      year rates of decline and year-to-year variability increased as the time-to
      extinction decreased. Together, these results provide key empirical insights into
      extinction dynamics, an important topic that has received extensive theoretical
      attention.

PMID- 16958869
TI  - Predator diversity strengthens trophic cascades in kelp forests by modifying
      herbivore behaviour.
AB  - Although human-mediated extinctions disproportionately affect higher trophic
      levels, the ecosystem consequences of declining diversity are best known for
      plants and herbivores. We combined field surveys and experimental manipulations
      to examine the consequences of changing predator diversity for trophic cascades
      in kelp forests. In field surveys we found that predator diversity was negatively
      correlated with herbivore abundance and positively correlated with kelp
      abundance. To assess whether this relationship was causal, we manipulated
      predator richness in kelp mesocosms, and found that decreasing predator richness
      increased herbivore grazing, leading to a decrease in the biomass of the giant
      kelp Macrocystis. The presence of different predators caused different herbivores
      to alter their behaviour by reducing grazing, such that total grazing was lowest
      at highest predator diversity. Our results suggest that declining predator
      diversity can have cascading effects on community structure by reducing the
      abundance of key habitat-providing species.

PMID- 16958870
TI  - Slow response of plant species richness to habitat loss and fragmentation.
AB  - We examined the response of vascular plant species richness to long-term habitat
      loss and fragmentation of Estonian calcareous grasslands (alvars). The current
      number of habitat specialist species in 35 alvars was not explained by their
      current areas and connectivities but it was explained by their areas and
      connectivities 70 years ago (R(2) = 0.27). We estimated the magnitude of
      extinction debt in local communities by assuming an equilibrium species richness
      in 14 alvars that had lost only a small amount of area and by applying this model
      to the remaining alvars, in which the average area has declined from 3.64 km(2)
      in the 1930s to 0.21 km(2) at present. The extinction debt estimated for
      individual alvars was around 40% of their current species number. Our conclusions
      are applicable to temperate grasslands in general, which have lost much area
      because of agricultural intensification and cessation of traditional management.

PMID- 16958871
TI  - Importance of species interactions to community heritability: a genetic basis to
      trophic-level interactions.
AB  - Recent community genetics studies have shown that specific genotypes of a host
      plant support distinct arthropod communities. Building upon these findings, we
      examined the hypothesis that a trophic community consisting of cottonwood trees,
      a galling herbivore and avian predators could also be related to the genetics of
      the host tree. We found genetic correlations among phytochemistry of individual
      tree genotypes, the density of a galling herbivore, and the intensity of avian
      predation on these herbivores. We detected significant broad-sense heritability
      of these interactions that range from H(B)2 = 0.70 to 0.83. The genetic basis of
      these interactions tended to increase across trophic levels suggesting that small
      genetic changes in the cottonwood phenotype could have major consequences at
      higher trophic levels affecting species interactions and energy flow. These
      findings show a heritable basis to trophic-level interactions indicating that
      there is a significant genetic basis to community composition and energy flow
      that is predictable by plant genotype. Our data clearly link plant genetics to
      patterns of avian foraging and show that species interactions are important
      components of community heritability and ecosystem processes. Overall, these data
      support the hypothesis that evolution of plant traits can alter trophic-level
      interactions and community composition.

PMID- 16958872
TI  - Herbivore control of annual grassland composition in current and future
      environments.
AB  - Selective consumption by herbivores influences the composition and structure of a
      range of plant communities. Anthropogenically driven global environmental
      changes, including increased atmospheric carbon dioxide (CO(2)), warming,
      increased precipitation, and increased N deposition, directly alter plant
      physiological properties, which may in turn modify herbivore consumption
      patterns. In this study, we tested the hypothesis that responses of annual
      grassland composition to global changes can be predicted exclusively from
      environmentally induced changes in the consumption patterns of a group of
      widespread herbivores, the terrestrial gastropods. This was done by: (1)
      assessing gastropod impacts on grassland composition under ambient conditions;
      (2) quantifying environmentally induced changes in gastropod feeding behaviour;
      (3) predicting how grassland composition would respond to global-change
      manipulations if influenced only by herbivore consumption preferences; and (4)
      comparing these predictions to observed responses of grassland community
      composition to simulated global changes. Gastropod herbivores consume nearly half
      of aboveground production in this system. Global changes induced species-specific
      changes in plant leaf characteristics, leading gastropods to alter the relative
      amounts of different plant types consumed. These changes in gastropod feeding
      preferences consistently explained global-change-induced responses of functional
      group abundance in an intact annual grassland exposed to simulated future
      environments. For four of the five global change scenarios, gastropod impacts
      explained > 50% of the quantitative changes, indicating that herbivore
      preferences can be a major driver of plant community responses to global changes.

PMID- 16958873
TI  - Regional enrichment of local assemblages is robust to variation in local
      productivity, abiotic gradients, and heterogeneity.
AB  - Theory predicts that the effects of regional richness on the richness of local
      communities may depend on the productivity, resource availability, and/or
      heterogeneity of local sites. Using the wetland plant communities of 50
      independent streams as 'regions', we tested whether: (1) local richness in 1-m(2)
      quadrats and 50-m stream segments was positively related to regional richness,
      even after environmental influences were considered; and (2) the effect of
      regional richness would interact with the effects of biomass, soil moisture,
      and/or heterogeneity on local richness. In models that explained up to 88% of
      variation in local richness, we found that richness at both local scales was
      positively related to regional richness, and that regional richness did not
      interact with any of the environmental gradients that also shaped local richness.
      We conclude that species availability from the regional pool may consistently
      enrich local communities, even while other constraints on local richness operate.

PMID- 16958874
TI  - Genetic variability in a population of arbuscular mycorrhizal fungi causes
      variation in plant growth.
AB  - Different species of arbuscular mycorrhizal fungi (AMF) alter plant growth and
      affect plant coexistence and diversity. Effects of within-AMF species or within
      population variation on plant growth have received less attention. High genetic
      variation exists within AMF populations. However, it is unknown whether genetic
      variation contributes to differences in plant growth. In our study, a population
      of AMF was cultivated under identical conditions for several generations prior to
      the experiments thus avoiding environmental maternal effects. We show that
      genetically different Glomus intraradices isolates from one AMF population
      significantly alter plant growth in an axenic system and in greenhouse
      experiments. Isolates increased or reduced plant growth meaning that plants
      potentially receive benefits or are subject to costs by forming associations with
      different individuals in the AMF population. This shows that genetic variability
      in AMF populations could affect host-plant fitness and should be considered in
      future research to understand these important soil organisms.

PMID- 16958876
TI  - Quantitative partitioning of regional and local processes shaping regional
      diversity patterns.
AB  - Much recent research explaining plant community diversity has focused on
      comparing the relative impacts of regional and local processes. We employed a
      novel analysis to quantify the effects of multiple regional and local processes
      on species richness, and to make quantitative comparisons of those effects across
      two sites that differ in plot-level species richness, productivity and
      environmental conditions. While abiotic stress and competition limited richness
      within the communities at both sites, only differences in the overall pool of
      species at the site, likely resulting from long-distance dispersal and climate
      fluctuations, explained the differences in plot-level richness between sites.
      Patterns in local richness may be driven by a temporal storage effect, with
      greater richness in the site with greater climatic variability. By identifying
      both the factors that impact diversity within communities and those that vary
      systematically across communities, our integrated approach provides a better
      understanding of regional diversity patterns.

PMID- 16958875
TI  - Conventional functional classification schemes underestimate the relationship
      with ecosystem functioning.
AB  - Studies linking the functional diversity of a biota to ecosystem functioning
      typically employ a priori classifications of species into hypothetically
      complementary groups. However, multiple alternate classifications exist in which
      the number of functional groups, the number of species per functional group, and
      the grouping of species differ from the a priori scheme. Without assessing the
      relative precision, or ability of an a priori scheme to accurately predict
      ecosystem functioning relative to its many alternatives, the validity and utility
      of analyses based on a single a priori classification scheme remains unclear. We
      examine the precision of a priori classifications used in 10 experimental
      grassland systems in Europe and the United States that have found evidence for a
      significant role of functional plant diversity in governing ecosystem function.
      The predictive precision of the a priori classifications employed in these
      studies was seldom significantly higher than the precision of random
      classifications. Post-hoc classification schemes that performed well in
      predicting ecosystem function resembled each other more with regard to species
      composition than average classifications, but there was still considerable
      variability in the manner in which these classification schemes grouped species.
      These results suggest that we need a more nuanced understanding of how the
      diversity of functional traits of species in an assemblage affects ecosystem
      functioning.

PMID- 16958877
TI  - Evolution of natural algal populations at elevated CO2.
AB  - Over the next century, it is expected that the concentration of CO(2) in the
      atmosphere will roughly double (Watson et al., 2001, Climate Change 2001: the
      Scientific Basis, Intergovernmental Panel on Climate Change, Geneva). Microbial
      populations, which have large population sizes and short generation times, may
      respond to CO(2) enrichment through genetic change. Here we describe microalgae
      isolated from the soil of natural CO(2) springs and compare these strains with
      lines of Chlamydomonas that were selected at elevated CO(2) in the laboratory.
      Both the laboratory and natural populations failed to evolve specific adaptations
      to elevated CO(2), and contain populations that grow poorly at ambient levels of
      CO(2). Laboratory and CO(2) spring populations also include lines whose growth
      rates are insensitive to CO(2). This demonstrates that, although laboratory
      selection experiments use simplified environments, the evolutionary responses
      that are seen following long-term CO(2) enrichment correspond to those found in
      natural populations that have experienced similar conditions.

PMID- 16958878
TI  - A null model of exotic plant diversity tested with exotic and native species-area
      relationships.
AB  - At large spatial scales, exotic and native plant diversity exhibit a strong
      positive relationship. This may occur because exotic and native species respond
      similarly to processes that influence diversity over large geographical areas. To
      test this hypothesis, we compared exotic and native species-area relationships
      within six North American ecoregions. We predicted and found that within
      ecoregions the ratio of exotic to native species richness remains constant with
      increasing area. Furthermore, we predicted that areas with more native species
      than predicted by the species-area relationship would have proportionally more
      exotics as well. We did find that these exotic and native deviations were highly
      correlated, but areas that were good (or bad) for native plants were even better
      (or worse) for exotics. Similar processes appear to influence exotic and native
      plant diversity but the degree of this influence may differ with site quality.

PMID- 16958879
TI  - Maladaptive changes in multiple traits caused by fishing: impediments to
      population recovery.
AB  - Some overharvested fish populations fail to recover even after considerable
      reductions in fishing pressure. The reasons are unclear but may involve genetic
      changes in life history traits that are detrimental to population growth when
      natural environmental factors prevail. We empirically modelled this process by
      subjecting populations of a harvested marine fish, the Atlantic silverside, to
      experimental size-biased fishing regimes over five generations and then measured
      correlated responses across multiple traits. Populations where large fish were
      selectively harvested (as in most fisheries) displayed substantial declines in
      fecundity, egg volume, larval size at hatch, larval viability, larval growth
      rates, food consumption rate and conversion efficiency, vertebral number, and
      willingness to forage. These genetically based changes in numerous traits
      generally reduce the capacity for population recovery.

PMID- 16958880
TI  - The missing Madagascan mid-domain effect.
AB  - Species richness varies enormously across geographical gradients, a well-known
      phenomenon for which there are many hypothesized explanations. One recent
      hypothesis uses null models to demonstrate that random re-distribution of
      species' ranges within a given domain leads to a 'mid-domain effect' (MDE):
      increasing species richness towards the centre of the area. Madagascar is
      especially well-suited for empirical evaluation of mid-domain models by virtue of
      its large endemic fauna and its clearly defined boundaries. Lees et al. [Biol. J.
      Linn. Soc.67 (1999) 529] observed patterns of species richness consistent with
      MDEs in the Madagascan rainforest (a slim, north-south belt). In this study, we
      test one-dimensional and two-dimensional mid-domain model predictions for the
      birds and mammals of the entire island of Madagascar. When only latitudinal
      extents of species' distribution are considered, patterns of richness in
      Madagascar show an MDE. However, this pattern disappears for both taxa after
      accounting for the tendency of latitudinal bands nearer the middle of the country
      to be larger. Two-dimensional mid-domain model predictions of species richness
      are qualitatively opposite to observed patterns. Instead, island-wide spatial
      gradients of species richness in Madagascar relate strongly to patterns of
      primary productivity and amount of remaining natural habitat. Earlier work that
      showed a mid-domain peak within the rainforest biome (effectively after
      controlling for climate and natural habitat) seems likely to have reflected
      methodological artefacts. The classic case in which MDEs should occur is, in
      fact, inconsistent with the mid-domain hypothesis.

PMID- 16958881
TI  - Ecological resistance, seed density and their interactions determine patterns of
      invasion in a California coastal grassland.
AB  - Relatively little experimental evidence is available regarding how ecological
      resistance and propagule density interact in their effects on the establishment
      of invasive exotic species. We examined the independent and interactive effects
      of neighbour cover (biotic resistance), winter vs. spring water addition (abiotic
      resistance) and seed density on the invasion of the European perennial grass
      Holcus lanatus into a California coastal grassland dominated by exotic annual
      grasses. We found that decreased competition from resident exotic grasses had no
      effect. In contrast, increased late-season water availability eroded the abiotic
      resistance offered by naturally dry conditions, facilitating invasion. Finally,
      watering treatment and seed density interacted strongly in determining seedling
      survival: while seedling mortality was close to 100% in ambient and winter water
      addition plots, survivor numbers increased with seed density in spring-watered
      plots. Thus, decreased abiotic resistance can amplify the effect of increased
      propagule density on seedling establishment, thereby increasing the likelihood of
      invasion.

PMID- 16958882
TI  - Evolution of body size in food webs: does the energetic equivalence rule hold?
AB  - The energetic equivalence rule (EER), which is derived from empirical
      observations linking population density and body size and from the allometric law
      linking metabolism and body size, predicts that the amount of energy used by the
      various species should be independent of body size. Here, we examine this
      hypothesis using a model that allows entire food webs to emerge from coevolution
      of interacting species. Body size influences both individual metabolism and
      interactions among species in the model. Overall, population density does
      decrease with body size roughly following a power law whose exponent is variable.
      We discuss this variability in the light of empirical data sets. The emerging
      relationship between the flux of resources exploited by the various species and
      their body size follows a decreasing power law, thus contradicting the EER. Our
      model emphasizes the importance of considering the influence of body size on
      species interactions in attempting to explain large-scale patterns related to
      body size.

PMID- 16958883
TI  - Can non-directional male mating preferences facilitate honest female
      ornamentation?
AB  - Recent studies have demonstrated male mate choice for female ornaments in species
      without sex-role reversal. Despite these empirical findings, little is known
      about the adaptive dynamics of female signalling, in particular the evolution of
      male mating preferences. The evolution of traits that signal mate quality is more
      complex in females than in males because females usually provide the bulk of
      resources for the developing offspring. Here, we investigate the evolution of
      male mating preferences using a mathematical model which: (i) specifically
      accounts for the fact that females must trade-off resources invested in ornaments
      with reproduction; and (ii) allows male mating preferences to evolve a non
      directional shape. The optimal adaptive strategy for males is to develop
      stabilizing mating preferences for female display traits to avoid females that
      either invests too many or too few resources in ornamentation. However, the
      evolutionary stability of this prediction is dependent upon the level of error
      made by females when allocating resources to either signal or fecundity.

PMID- 16958884
TI  - Niche breadth, competitive strength and range size of tree species: a trade-off
      based framework to understand species distribution.
AB  - Understanding the mechanisms causing latitudinal gradients in species richness
      and species range size is a central issue in ecology, particularly in the current
      context of global climate change. Different hypotheses have been put forward to
      explain these patterns, emphasizing climatic variability, energy availability and
      competition. Here we show, using a comparative analysis controlling for phylogeny
      on 234 temperate/boreal tree species, that these hypotheses can be included into
      a single framework in an attempt to explain latitudinal gradients in species
      range size. We find that species tend to have larger ranges when (i) closer to
      the poles, (ii) successionally seral, (iii) having small and light seeds, and
      (iv) having short generations. The patterns can simply be explained by energy
      constraints associated with different life-history strategies. Overall, these
      findings shed a new light on our understanding of species distribution and
      biodiversity patterns, bringing new insights into underlying large-scale
      evolutionary processes.

PMID- 16958885
TI  - Assessing environmental risks of transgenic plants.
AB  - By the end of the 1980s, a broad consensus had developed that there were
      potential environmental risks of transgenic plants requiring assessment and that
      this assessment must be done on a case-by-case basis, taking into account the
      transgene, recipient organism, intended environment of release, and the frequency
      and scale of the intended introduction. Since 1990, there have been gradual but
      substantial changes in the environmental risk assessment process. In this review,
      we focus on changes in the assessment of risks associated with non-target species
      and biodiversity, gene flow, and the evolution of resistance. Non-target risk
      assessment now focuses on risks of transgenic plants to the intended local
      environment of release. Measurements of gene flow indicate that it occurs at
      higher rates than believed in the early 1990s, mathematical theory is beginning
      to clarify expectations of risks associated with gene flow, and management
      methods are being developed to reduce gene flow and possibly mitigate its
      effects. Insect pest resistance risks are now managed using a high-dose/refuge or
      a refuge-only strategy, and the present research focuses on monitoring for
      resistance and encouraging compliance to requirements. We synthesize previous
      models for tiering risk assessment and propose a general model for tiering.
      Future transgenic crops are likely to pose greater challenges for risk
      assessment, and meeting these challenges will be crucial in developing a
      scientifically coherent risk assessment framework. Scientific understanding of
      the factors affecting environmental risk is still nascent, and environmental
      scientists need to help improve environmental risk assessment.

PMID- 16958886
TI  - The imprint of the geographical, evolutionary and ecological context on species
      area relationships.
AB  - Species-area relationships (SAR) are fundamental in the understanding of
      biodiversity patterns and of critical importance for predicting species
      extinction risk worldwide. Despite the enormous attention given to SAR in the
      form of many individual analyses, little attempt has been made to synthesize
      these studies. We conducted a quantitative meta-analysis of 794 SAR, comprising a
      wide span of organisms, habitats and locations. We identified factors reflecting
      both pattern-based and dynamic approaches to SAR and tested whether these factors
      leave significant imprints on the slope and strength of SAR. Our analysis
      revealed that SAR are significantly affected by variables characterizing the
      sampling scheme, the spatial scale, and the types of organisms or habitats
      involved. We found that steeper SAR are generated at lower latitudes and by
      larger organisms. SAR varied significantly between nested and independent
      sampling schemes and between major ecosystem types, but not generally between the
      terrestrial and the aquatic realm. Both the fit and the slope of the SAR were
      scale-dependent. We conclude that factors dynamically regulating species richness
      at different spatial scales strongly affect the shape of SAR. We highlight
      important consequences of this systematic variation in SAR for ecological theory,
      conservation management and extinction risk predictions.

PMID- 16958887
TI  - The impacts of climate change in coastal marine systems.
AB  - Anthropogenically induced global climate change has profound implications for
      marine ecosystems and the economic and social systems that depend upon them. The
      relationship between temperature and individual performance is reasonably well
      understood, and much climate-related research has focused on potential shifts in
      distribution and abundance driven directly by temperature. However, recent work
      has revealed that both abiotic changes and biological responses in the ocean will
      be substantially more complex. For example, changes in ocean chemistry may be
      more important than changes in temperature for the performance and survival of
      many organisms. Ocean circulation, which drives larval transport, will also
      change, with important consequences for population dynamics. Furthermore,
      climatic impacts on one or a few 'leverage species' may result in sweeping
      community-level changes. Finally, synergistic effects between climate and other
      anthropogenic variables, particularly fishing pressure, will likely exacerbate
      climate-induced changes. Efforts to manage and conserve living marine systems in
      the face of climate change will require improvements to the existing predictive
      framework. Key directions for future research include identifying key demographic
      transitions that influence population dynamics, predicting changes in the
      community-level impacts of ecologically dominant species, incorporating
      populations' ability to evolve (adapt), and understanding the scales over which
      climate will change and living systems will respond.

PMID- 16958888
TI  - Mixed biodiversity benefits of agri-environment schemes in five European
      countries.
AB  - Agri-environment schemes are an increasingly important tool for the maintenance
      and restoration of farmland biodiversity in Europe but their ecological effects
      are poorly known. Scheme design is partly based on non-ecological considerations
      and poses important restrictions on evaluation studies. We describe a robust
      approach to evaluate agri-environment schemes and use it to evaluate the
      biodiversity effects of agri-environment schemes in five European countries. We
      compared species density of vascular plants, birds, bees, grasshoppers and
      crickets, and spiders on 202 paired fields, one with an agri-environment scheme,
      the other conventionally managed. In all countries, agri-environment schemes had
      marginal to moderately positive effects on biodiversity. However, uncommon
      species benefited in only two of five countries and species listed in Red Data
      Books rarely benefited from agri-environment schemes. Scheme objectives may need
      to differentiate between biodiversity of common species that can be enhanced with
      relatively simple modifications in farming practices and diversity or abundance
      of endangered species which require more elaborate conservation measures.

PMID- 16958891
TI  - Ecosystem engineers as selective agents: the effects of leaf litter on emergence
      time and early growth in Impatiens capensis.
AB  - By physically modifying the abiotic environment, ecosystem engineers can have
      dramatic effects on the distribution and abundance of species in a community.
      However, ecosystem engineering can also change the selective environment and
      evolutionary dynamics of affected species, although this remains relatively
      understudied. Here, we examine the potential for an ecosystem engineer - oak
      trees - to affect the evolutionary dynamics of the herbaceous, understory annual,
      Impatiens capensis, through leaf litter deposition. Using a quantitative genetic
      experimental approach, we found that: (i) the presence of leaf litter
      significantly affected a suite of germination, growth and phenological traits in
      I. capensis; (ii) I. capensis does not exhibit performance trade-offs across
      litter and bare soil environments in the form of negative across-environment
      genetic correlations; (iii) the presence or absence of leaf litter significantly
      alters the pattern of natural selection germination timing and hypocotyl length;
      and (iv) the frequency of leaf litter environments can dramatically change which
      combinations of hypocotyl length lead to highest mean fitness across both bare
      soil and leaf litter environments. More generally, our results demonstrate the
      potential for ecosystem engineers to alter both the ecological and the
      evolutionary dynamics of the species they affect.

PMID- 16958892
TI  - Local and regional scale recovery of Diadema promotes recruitment of
      scleractinian corals.
AB  - The phase change from coral to macroalgal dominance on many Caribbean reefs was
      exacerbated by the mortality of the echinoid Diadema antillarum in 1983-1984, and
      until recently, this sea urchin has remained rare on reefs throughout the western
      Atlantic. By the late 1990s, Diadema started to reappear in large numbers on some
      Jamaican reefs, and by 2000, the high densities were correlated with
      significantly greater abundances of juvenile corals. Here, we show that dense
      populations of Diadema now occur over a multi-kilometre-wide scale at six
      locations scattered along a 4100 km arc across the entire Caribbean. In all
      cases, these dense populations are found in shallow water (< 6 m depth) on outer
      reef communities and are associated with reduced macroalgal cover and enhanced
      coral recruitment. We conclude that population recovery of Diadema is occurring
      at both local and regional scales, and that grazing by this echinoid is creating
      conditions favouring the recruitment of corals.

PMID- 16958893
TI  - Habitat loss and the structure of plant-animal mutualistic networks.
AB  - Recent papers have described the structure of plant-animal mutualistic networks.
      However, no study has yet explored the dynamical implications of network
      structure for the persistence of such mutualistic communities. Here, we develop a
      patch-model of a whole plant-animal community and explore its persistence. To
      assess the role of network structure, we build three versions of the model. In
      the first version, we use the exact network of interactions of two real
      mutualistic communities. In the other versions, we randomize the observed network
      of interactions using two different null models. We show that the community
      response to habitat loss is affected by network structure. Real communities start
      to decay sooner than random communities, but persist for higher destruction
      levels. There is a destruction threshold at which the community collapses. Our
      model is the first attempt to describe the dynamics of whole mutualistic
      metacommunities interacting in realistic ways.

PMID- 16958894
TI  - Linking species-area and species-energy relationships in Drosophila microcosms.
AB  - Resource availability is an important constraint on community structure. Some
      authors have suggested it conceptually links two of the most basic patterns in
      ecology, the species-area relationship and the latitudinal gradient in species
      richness. I present the first experimental test of this conjecture, by
      manipulating both the area and resource concentration of artificial larval
      drosophilid fly habitats and then allowing colonization from a natural species
      pool. Both the abundance and species richness of these habitats depended upon the
      total quantity of resources available, regardless of whether those resources were
      contained within smaller high-quality habitats or larger poor-quality habitats.
      While the intercepts of species-area relationships varied with resource
      concentration, they all collapsed onto the same species-energy curve. These
      results support the view that energetic constraints are of fundamental importance
      in structuring ecological communities, and that such constraints may even help
      explain ecological patterns such as the species-area relationship that do not
      explicitly address resource availability.

PMID- 16958895
TI  - Early Cambrian food webs on a trophic knife-edge? A hypothesis and preliminary
      data from a modern stromatolite-based ecosystem.
AB  - Here we use the theory of ecological stoichiometry to propose and provide a
      preliminary test of a novel hypothesis that the Cambrian 'explosion' may have
      been triggered by changes in circulating P availability in the biosphere. We
      exposed living stromatolites from a spring-fed stream in Mexico to a gradient of
      P enrichment to examine subsequent effects on stromatolite C : P ratio and on the
      primary grazer, an endemic snail. Consistent with a previously hypothesized
      stoichiometric 'knife-edge', snail performance was maximal at intermediate P
      enrichment, indicating in situ stoichiometric constraints because of high
      stromatolite C : P ratio along with high sensitivity to excessive P intake. These
      results are consistent with the idea that stoichiometric constraints may have
      delayed the evolutionary proliferation of animals in ancient stromatolite
      dominated ecosystems and also suggest that high food P content can significantly
      impair consumers. We propose that ecosystem P availability may have impacted both
      the expansion and decline of animal taxa in the history of life.

PMID- 16958896
TI  - Parallel responses of species and genetic diversity to El Nino Southern
      Oscillation-induced environmental destruction.
AB  - Species diversity within communities and genetic diversity within species are two
      fundamental levels of biodiversity. Positive relationships between species
      richness and within-species genetic diversity have recently been documented
      across natural and semi-natural habitat islands, leading Vellend to suggest a
      novel macro-ecological pattern termed the species-genetic diversity correlation.
      We tested whether this prediction holds for areas affected by recent habitat
      disturbance using butterfly communities in east Kalimantan, Indonesia. Here, we
      show that both strong spatial and temporal correlations exist between species and
      allelic richness across rainforest habitats affected by El Nino Southern
      Oscillation-induced disturbance. Coupled with evidence that changes in species
      richness are a direct result of local extirpation and lower recruitment, these
      data suggest that forces governing variation at the two levels operate over
      parallel and short timescales, with implications for biodiversity recovery
      following disturbance. Remnant communities may be doubly affected, with
      reductions in species richness being associated with reductions in genetic
      diversity within remnant species.

PMID- 16958897
TI  - Rising variance: a leading indicator of ecological transition.
AB  - Regime shifts are substantial, long-lasting reorganizations of complex systems,
      such as ecosystems. Large ecosystem changes such as eutrophication, shifts among
      vegetation types, degradation of coral reefs and regional climate change often
      come as surprises because we lack leading indicators for regime shifts. Increases
      in variability of ecosystems have been suggested to foreshadow ecological regime
      shifts. However, it may be difficult to discern variability due to impending
      regime shift from that of exogenous drivers that affect the ecosystem. We
      addressed this problem using a model of lake eutrophication. Lakes are subject to
      fluctuations in recycling associated with regime shifts, as well as fluctuating
      nutrient inputs. Despite the complications of noisy inputs, increasing
      variability of lake-water phosphorus was discernible prior to the shift to
      eutrophic conditions. Simulations show that rising standard deviation (SD) could
      signal impending shifts about a decade in advance. The rising SD was detected by
      studying variability around predictions of a simple time-series model, and did
      not depend on detailed knowledge of the actual ecosystem dynamics.

PMID- 16958898
TI  - Antagonistic effects of seed dispersal and herbivory on plant migration.
AB  - The two factors that determine plant migration rates - seed dispersal and
      population growth - are generally treated independently, despite the fact that
      many animals simultaneously enhance plant migration rate via seed dispersal, and
      decrease it via negative effects of herbivory on population growth. Using
      extensive empirical data, we modelled the antagonistic effects of seed dispersal
      and herbivory by white-tailed deer on potential migration rates of Trillium
      grandiflorum, a forest herb in eastern North America. This novel antagonistic
      interaction is illustrated by maximum migration rates occurring at intermediate,
      but low herbivory (< 15%). Assuming herbivory < 20% and favourable conditions for
      population growth during post-glacial migration, seed dispersal by deer can
      explain rates of migration achieved in the past, in contrast to previous models
      of forest herb migration. However, relatively unfavourable conditions for
      population growth and increasingly intense herbivory by deer may compromise plant
      migration in the face of present and future climate change.

PMID- 16958899
TI  - Temporal autocorrelation and stochastic population growth.
AB  - How much does environmental autocorrelation matter to the growth of structured
      populations in real life contexts? Interannual variances in vital rates certainly
      do, but it has been suggested that between-year correlations may not. We present
      an analytical approximation to stochastic growth rate for multistate Markovian
      environments and show that it is accurate by testing it in two empirically based
      examples. We find that temporal autocorrelation has sizeable effect on growth
      rates of structured populations, larger in many cases than the effect of
      interannual variability. Our approximation defines a sensitivity to
      autocorrelated variability, showing how demographic damping and environmental
      pattern interact to determine a population's stochastic growth rate.

PMID- 16958900
TI  - Insect predators affect plant resistance via density- and trait-mediated indirect
      interactions.
AB  - Predators can affect herbivores both through direct consumption (density-mediated
      interactions) and by changing behavioural, physiological or morphological
      attributes of the prey (trait-mediated interactions). These effects on the
      herbivore can in turn affect the plant through density- and trait-mediated
      indirect interactions (DMIIs and TMIIs). While the effects of DMIIs and TMIIs
      imposed by predators has been shown to influence plant density and plant
      communities, we know little about the effects on plant quality. In addition, the
      DMII and TMII components of the predator may influence each other so that the
      total effect of the predator on the plant is not simply the sum of the DMII and
      TMII. We examined DMIIs and TMIIs between a stinkbug predator and a caterpillar,
      and show how these interactions affect plant quality, as measured by damage,
      resistance to herbivores, and a defence chemical, peroxidase. We used novel
      methods to estimate the independent and non-additive contribution of DMIIs and
      TMIIs to the plant phenotype. Both predator-induced DMIIs and TMIIs caused
      decreases in the amount of caterpillar herbivory on plants; a strong non-additive
      effect between the two resulted from redundancy in their effects. TMIIs initiated
      by the predator were primarily responsible for a decrease in induced plant
      resistance. However, DMIIs predominated for reducing the production of
      peroxidase. These data demonstrate how DMIIs and TMIIs initiated by predators
      cascade through tri-trophic interactions to affect plant damage and induced
      resistance.

PMID- 16958901
TI  - Plant-fungus mutualism affects spider composition in successional fields.
AB  - Mutualistic symbionts are widespread in plants and may have strong, bottom-up
      influences on community structure. Here we show that a grass-endophyte mutualism
      shifts the composition of a generalist predator assemblage. In replicated,
      successional fields we manipulated endophyte infection by Neotyphodium
      coenophialum in a dominant, non-native plant (Lolium arundinaceum). We compared
      the magnitude of the endophyte effect with manipulations of thatch biomass, a
      habitat feature of known importance to spiders. The richness of both spider
      families and morphospecies was greater in the absence of the endophyte, although
      total spider abundance was not affected. Thatch removal reduced both spider
      abundance and richness, and endophyte and thatch effects were largely additive.
      Spider families differed in responses, with declines in Linyphiidae and
      Thomisidae due to the endophyte and declines in Lycosidae due to thatch removal.
      Results demonstrate that the community impacts of non-native plants can depend on
      plants' mutualistic associates, such as fungal endophytes.

PMID- 16958902
TI  - Evolutionary responses of natives to introduced species: what do introductions
      tell us about natural communities?
AB  - Biological invasions dramatically affect the distribution, abundance and
      reproduction of many native species. Because of these ecological effects, exotic
      species can also influence the evolution of natives exposed to novel interactions
      with invaders. Evolutionary changes in natives in response to selection from
      exotics are usually overlooked, yet common responses include altered anti
      predator defenses, changes in the spectrum of resources and habitats used, and
      other adaptations that allow native populations to persist in invaded areas.
      Whether a native population is capable of responding evolutionarily to selection
      from invaders will depend on the demographic impact of the invader, the genetic
      architecture and genetic variability of the native population and potentially the
      history of previous invasions. In some cases, natives will fail to evolve or
      otherwise adapt, and local or global extinction will result. In other cases,
      adaptive change in natives may diminish impacts of invaders and potentially
      promote coexistence between invaders and natives. Here, we review the evidence
      for evolutionary responses of native species to novel community members. We also
      discuss how the effects of introduced species may differ from those caused by
      natural range expansions of native species. Notably, introduced species may come
      from remote biotas with no previous evolutionary history with the native
      community. In addition, the rate of addition of introduced species into
      communities is much greater than all but the most extreme cases of historical
      biotic exchange. Understanding the evolutionary component of exotic/native
      species interactions is critical to recognizing the long-term impacts of
      biological invasions, and to understanding the role of evolutionary processes in
      the assembly and dynamics of natural communities.

PMID- 16958903
TI  - Strategies of aerobic ammonia-oxidizing bacteria for coping with nutrient and
      oxygen fluctuations.
AB  - In most natural environments as well as in engineered environments, such as
      wastewater treatment plants, ammonia-oxidizing bacteria (AOB) experience
      fluctuating substrate concentrations. Several physiological traits, such as low
      maintenance energy demand and decay rate, cell-to-cell communication, cell
      mobility, stable enzymes and RNAs, could allow AOB to maintain themselves under
      unfavourable circumstances. This review examines whether AOB possess such traits
      and how these traits might offer advantages over competing organisms such as
      heterotrophic bacteria during periods of starvation. In addition, within the AOB
      groups, differences exist in adaptation to and competitiveness under conditions
      of high or low ammonia or oxygen concentrations. Because these findings are of
      importance with regard to the ecology and activity of AOB in natural and
      engineered environments, concluding remarks are directed towards future research
      objectives that may clarify unanswered questions, thereby contributing to the
      general knowledge of the ecology and activity of ammonia oxidizers.

PMID- 16958904
TI  - The uptake of amino acids by the cyanobacterium Planktothrix rubescens is
      stimulated by light at low irradiances.
AB  - The rates of uptake of five amino acids--alanine, glutamate, glycine, leucine and
      serine--by axenic cultures of the cyanobacterium Planktothrix rubescens were
      measured over a range of irradiances using the (14)C-labelled amino acids at the
      nanomolar concentrations observed in Lake Zurich. The rates in the light exceeded
      the dark rates by as much as two- to ninefold. The light-affinity constants for
      stimulation were similar, indicating a similar process for each of the five amino
      acids. The E(k) (light saturation irradiance) for light stimulation was only 1
      micromol m(-2) s(-1), less than the compensation point for photosynthesis and
      autotrophic growth, and much lower than the E(k) for either process. The E(k) for
      amino acid uptake was also less than the irradiance at which filaments obtain
      neutral buoyancy, which determines the depth at which they stratify and the
      irradiance they receive. This indicates that stimulation of amino acid uptake by
      light of low irradiances provides a mechanism for supplementing growth of
      filaments stratifying deep in the metalimnion, which, while able to grow at low
      irradiances, are often left with insufficient light to sustain them. Acetate
      uptake was also stimulated by light, but the kinetics differed.

PMID- 16958905
TI  - Dynamics and estimates of growth and loss rates of bacterioplankton in a
      temperate freshwater system.
AB  - The growth rate and losses of bacterioplankton in the epilimnion of an oligo
      mesotrophic reservoir were simultaneously estimated using three different methods
      for each process. Bacterial production was determined by means of the tritiated
      thymidine incorporation method, the dialysis bag method and the dilution method,
      while bacterial mortality was assessed with the dilution method, the
      disappearance of thymidine-labeled natural cells and ingestion of fluorescent
      bacterial tracers by heterotrophic flagellates. The different methods used to
      estimate bacterial growth rates yielded similar results. On the other hand, the
      mortality rates obtained with the dilution method were significantly lower than
      those obtained with the use of thymidine-labeled natural cells. The bacterial
      ingestion rate by flagellates accounted on average for 39% of total bacterial
      mortality estimated by the dilution method, but this value fell to 5% when the
      total mortality was measured by the thymidine-labeling method. Bacterial
      abundance and production varied in opposite phase to flagellate abundance and the
      various bacterial mortality rates. All this points to the critical importance of
      methodological aspects in the elaboration of quantitative models of matter and
      energy flows over the time through microbial trophic networks in aquatic systems,
      and highlights the role of bacterioplankton as a source of carbon for higher
      trophic levels in the studied system.

PMID- 16958906
TI  - Compensatory growth of Phanerochaete velutina mycelial systems grazed by Folsomia
      candida (Collembola).
AB  - Phanerochaete velutina is a major agent of wood decomposition in temperate
      forests. It grows out of woody resources in search of other resources and is then
      vulnerable to grazing by invertebrates. The aim of this study was to determine
      how continuous grazing and grazing for only 2 days by different densities of
      collembola, Folsomia candida, affect mycelial development (radial extension,
      hyphal coverage and fractal dimension) of P. velutina growing across non-sterile
      soil. High density (80 collembola) continuous grazing resulted in different
      mycelial foraging patterns compared to controls and lower density (20 and 40
      collembola) continuous grazing: radial extension rate was reduced from 8.4 mm
      day(-1) (control) to 6.9 mm day(-1) (80 collembola), hyphal coverage was reduced
      to 81% of controls and mass fractal dimension increased from 1.68 (control) to
      1.72 (80 collembola). There was evidence of over-compensatory growth: when high
      density grazing ceased the new growth was considerably greater (38%) than in
      controls. Grazing also resulted in growth stimulation: at low density continuous
      grazing (20 collembola) hyphal coverage was 15.6% greater than in controls. The
      ecological implications of compensatory and stimulatory growth in fungal
      invertebrate interactions are considered.

PMID- 16958907
TI  - Responses of antioxidants in the lichen Ramalina lacera may serve as an early
      warning bioindicator system for the detection of air pollution stress.
AB  - The aim of this study was to identify, in the lichen Ramalina lacera,
      antioxidants that could provide indications of air pollution stress, and respond
      earlier than traditionally used structural/physiological parameters. The
      pollution-sensitive lichen R. lacera was transplanted from its relatively
      unpolluted natural habitat to two air-polluted sites for a period of up to 6
      months. The superoxide dismutase and catalase activities, total water- and lipid
      soluble low-molecular-weight antioxidant capacities and chlorophyll b/chlorophyll
      a ratios were assessed every 6 weeks. The earliest signs of oxidative stress were
      detected in the activities of fungal copper/zinc-superoxide dismutase, algal iron
      superoxide dismutase and water-soluble low-molecular-weight antioxidants, which
      increased significantly as early as 42 days after exposure to pollution. Catalase
      activity increased in lichens transplanted to the polluted sites after 90 days.
      All activities decreased towards the end of the experiment. The impact of air
      pollution on R. lacera, using the traditionally employed parameter of chlorophyll
      b/chlorophyll a ratio, was only detected after 6 months of exposure to air
      pollution. Our results indicate that antioxidant parameters may serve as improved
      early-warning indicators of air pollution stress in lichens.

PMID- 16958908
TI  - Earthworms as vectors of Escherichia coli O157:H7 in soil and vermicomposts.
AB  - Survival and movement of Escherichia coli O157:H7 in both soil and vermicompost
      is of concern with regards to human health. Whilst it is accepted that E. coli
      O157:H7 can persist for considerable periods in soils, it is not expected to
      survive thermophilic composting processes. However, the natural behavior of
      earthworms is increasingly utilized for composting (vermicomposting), and the
      extent to which earthworms promote the survival and dispersal of the bacterium
      within such systems is unknown. The faecal material produced by earthworms
      provides a ready supply of labile organic substrates to surrounding microbes
      within soil and compost, thus promoting microbial activity. Earthworms can also
      cause significant movement of organisms through the channels they form. Survival
      and dispersal of E. coli O157:H7 were monitored in contaminated soil and farmyard
      manure subjected to earthworm digestion over 21 days. Our findings lead to the
      conclusion that anecic earthworms such as Lumbricus terrestris may significantly
      aid vertical movement of E. coli O157 in soil, whereas epigeic earthworms such as
      Dendrobaena veneta significantly aid lateral movement within compost. Although
      the presence of earthworms in soil and compost may aid proliferation of E. coli
      O157 in early stages of contamination, long-term persistence of the pathogen
      appears to be unaffected.

PMID- 16958909
TI  - Prokaryotic community composition and biogeochemical processes in deep
      subseafloor sediments from the Peru Margin.
AB  - The community compositions of Bacteria and Archaea were investigated in deep, sub
      seafloor sediments from the highly productive Peru Margin (ODP Leg 201, sites
      1228 and 1229, c. 25 km apart) down to nearly 200 m below the seafloor using
      taxonomic (16S rRNA) and functional (mcrA and dsrA) gene markers. Bacterial and
      archaeal groups identified from clone libraries of 16S rRNA gene sequences at
      site 1229 agreed well with sequences amplified from bands excised from denaturing
      gradient gel electrophoresis (DGGE) depth profiles, with the exception of the
      Miscellaneous Crenarchaeotic Group (MCG). This suggested that the prokaryotic
      community at site 1228, obtained from DGGE profiling alone, was reliable. Sites
      were dominated by Bacteria in the Gammaproteobacteria, Chloroflexi (green non
      sulphur bacteria) and Archaea in the MCG and South African Gold Mine
      Euryarchaeotic Group, although community composition changed with depth. The
      candidate division JS1 was present throughout both sites but was not dominant.
      The populations identified in the Peru Margin sediments consisted mainly of
      prokaryotes found in other deep subsurface sediments, and were more similar to
      communities from the Sea of Okhotsk (pelagic clays) than to those from the low
      organic carbon Nankai Trough sediments. Despite broad similarities in the
      prokaryotic community at the two sites, there were some differences, as well as
      differences in activity and geochemistry. Methanogens (mcrA) within the
      Methanosarcinales and Methanobacteriales were only found at site 1229 (4 depths
      analysed), whereas sulphate-reducing prokaryotes (dsrA) were only found at site
      1228 (one depth), and these terminal-oxidizing prokaryotes may represent an
      active community component present at low abundance. This study clearly
      demonstrates that the deep subsurface sediments of the Peru Margin have a large
      diverse and metabolically active prokaryotic population.

PMID- 16958910
TI  - Analysis of DGGE profiles to explore the relationship between prokaryotic
      community composition and biogeochemical processes in deep subseafloor sediments
      from the Peru Margin.
AB  - The aim of this work was to relate depth profiles of prokaryotic community
      composition with geochemical processes in the deep subseafloor biosphere at two
      shallow-water sites on the Peru Margin in the Pacific Ocean (ODP Leg 201, sites
      1228 and 1229). Principal component analysis of denaturing gradient gel
      electrophoresis banding patterns of deep-sediment Bacteria, Archaea,
      Euryarchaeota and the novel candidate division JS1, followed by multiple
      regression, showed strong relationships with prokaryotic activity and
      geochemistry (R(2)=55-100%). Further correlation analysis, at one site, between
      the principal components from the community composition profiles for Bacteria and
      12 other variables quantitatively confirmed their relationship with activity and
      geochemistry, which had previously only been implied. Comparison with previously
      published cell counts enumerated by fluorescent in situ hybridization with rRNA
      targeted probes confirmed that these denaturing gradient gel electrophoresis
      profiles described an active prokaryotic community.

PMID- 16958911
TI  - Diversity of culturable bacteria in the mucus of the Red Sea coral Fungia
      scutaria.
AB  - Coral reefs are the most biodiverse of all marine ecosystems. Bacteria are known
      to be abundant and active in seawater around corals, inside coral tissues, and
      within their surface microlayer. Very little is known, however, about the
      structure, composition and maintenance of these bacterial communities. In the
      current study we characterize the culturable bacterial community within the mucus
      of healthy specimens of the Red Sea solitary coral Fungia scutaria. This was
      achieved using culture-based methods and molecular techniques for the
      identification of the bacterial isolates. More than 30% of the isolated bacteria
      were novel species and a new genus. The culturable heterotrophic bacterial
      community of the mucus of this coral is composed mainly of the bacterial groups
      Gammaproteobacteria, Alphaproteobacteria and of Actinobacteria. This study
      provides the first evidence of actinomycetes isolated from corals.

PMID- 16958912
TI  - Spatial variability in the abundance and composition of the free-living
      bacterioplankton community in the pelagic zone of Lake Bourget (France).
AB  - Spatial variations in the abundance and diversity of the free-living
      bacterioplankton community of a large Alpine lake, Lake Bourget (France), were
      investigated in the pelagic zone by means of two two-dimensional samplings taken
      in 2003. Lake-water samples were collected in winter during water mixing, and in
      early summer during stratification. The population abundance in each sample was
      determined by flow cytometry. Denaturing gradient gel electrophoresis of PCR
      amplified 16S rRNA gene fragments from organisms measuring less than 2 mum was
      used to assess eubacterioplankton community composition. In winter, no obvious
      differences were observed in either the abundance or the diversity of the
      bacterial community, on either the horizontal or the vertical scales. The only
      influence detected was that of river water input, but this was at a very minor
      scale relative to the surface area of the lake. In early summer, changes were
      found in the community composition on the vertical scale related to the thermal
      stratification of the water column. There were also marked differences on the
      horizontal scale at 15 m depth due to internal waves. The implications of these
      findings for sampling strategies are very important from the perspective of
      comparative studies of free-living bacterial community diversity and functioning
      in large and deep lakes.

PMID- 16958913
TI  - Bacterial diversity of an acidic Louisiana groundwater contaminated by dense
      nonaqueous-phase liquid containing chloroethanes and other solvents.
AB  - Bacterial concentration and diversity was assessed in a moderately acidic (pH
      5.1) anaerobic groundwater contaminated by chlorosolvent-containing DNAPL at a
      Superfund site located near Baton Rouge, Louisiana. Groundwater analysis revealed
      a total aqueous-phase chlorosolvent concentration exceeding 1000 mg L(-1),
      including chloroethanes, vinyl chloride, 1,2-dichloropropane, and hexachloro-1,3
      butadiene as the primary contaminants. Direct counting of stained cells revealed
      more than 3 x 10(7) cells mL(-1) in the groundwater, with 58% intact and
      potentially viable. Universal and 'Dehalococcoides'-specific 16S rRNA gene
      libraries were created and analyzed. Universal clones were grouped into 18
      operational taxonomic units (OTUs), which were dominated by low-G+C Gram-positive
      bacteria (62%) and included several as yet uncultured or undescribed organisms.
      Several unique 16S rRNA gene sequences closely related to Dehalococcoides
      ethenogenes were detected. Anaerobically grown isolates (168 in total) were also
      sequenced. These were phylogenetically grouped into 18 OTUs, of which only three
      were represented in the clone library. Phylogenetic analysis of isolates and the
      clone sequences revealed close relationships with dechlorinators, fermenters, and
      hydrogen producers. Despite acidic conditions and saturation or near-saturation
      chlorosolvent concentrations, the data presented here demonstrate that large
      numbers of novel bacteria are present in groundwater within the DNAPL source
      zone, and the population appears to contain bacterial components necessary to
      carry out reductive dechlorination.

PMID- 16958914
TI  - Novel upper meta-pathway extradiol dioxygenase gene diversity in polluted soil.
AB  - For the determination of the catabolic community diversity that is related to
      biodegradation potential, we developed a protocol for the assessment of catabolic
      marker genes in polluted soils. Primers specific to upper pathway extradiol
      dioxygenase genes were designed which amplified a 469-bp product from
      Sphingomonas sp. HV3. The constructed primers were used in PCR amplification of
      upper pathway ring cleavage genes from DNA directly isolated from a mineral oil
      polluted landfill site, a mineral oil landfarming site and a birch rhizosphere
      associated soil that was either artificially polluted with a PAH mixture or not
      polluted. Amplicons were cloned and subjected to restriction fragment length
      polymorphism analysis dividing the HhaI-digested products into operational
      taxonomic units. Altogether 26 different operational taxonomic units were
      detected with the sequence similarity to known catabolic genes of Alpha-, Beta-,
      and Gammaproteobacteria. Phylogenetic analysis divided the operational taxonomic
      units from the polluted soils into seven clusters. Two contained exclusively
      sequences with no close homologues in the database, therefore representing novel
      catabolic genes. This large proportion of novel extradiol sequences shows that
      there is an extensive unknown catabolic diversity in polluted environments.

PMID- 16958915
TI  - Phylogenetic analysis of a biofilm bacterial population in a water pipeline in
      the Gulf of Mexico.
AB  - The aim of this study was to assess the bacterial diversity associated with a
      corrosive biofilm in a steel pipeline from the Gulf of Mexico used to inject
      marine water into the oil reservoir. Several aerobic and heterotrophic bacteria
      were isolated and identified by 16S rRNA gene sequence analysis. Metagenomic DNA
      was also extracted to perform a denaturing gradient gel electrophoresis analysis
      of ribosomal genes and to construct a 16S rRNA gene metagenomic library.
      Denaturing gradient gel electrophoresis profiles and ribosomal libraries
      exhibited a limited bacterial diversity. Most of the species detected in the
      ribosomal library or isolated from the pipeline were assigned to Proteobacteria
      (Halomonas spp., Idiomarina spp., Marinobacter aquaeolei, Thalassospira sp.,
      Silicibacter sp. and Chromohalobacter sp.) and Bacilli (Bacillus spp. and
      Exiguobacterium spp.). This is the first report that associates some of these
      bacteria with a corrosive biofilm. It is relevant that no sulfate-reducing
      bacteria were isolated or detected by a PCR-based method. The diversity and
      relative abundance of bacteria from water pipeline biofilms may contribute to an
      understanding of the complexity and mechanisms of metal corrosion during marine
      water injection in oil secondary recovery.

PMID- 16958916
TI  - Hypersensitivity to titanium osteosynthesis with impaired fracture healing,
      eczema, and T-cell hyperresponsiveness in vitro: case report and review of the
      literature.
AB  - There are very few reports on hypersensitivity reactions in association with
      titanium-based materials so that the existence of allergy to titanium is still
      put in question. We report on a patient in whom impaired fracture healing and
      eczema localized to the perioperative area developed upon titanium-based
      osteosynthesis. Patch testing gave no reactions to titanium nor to nickel,
      chromium, or cobalt. However, in the lymphocyte transformation test, the
      patient's lymphocytes showed markedly enhanced proliferation in vitro to
      titanium. After removal of the titanium material, fracture healing was achieved
      and the eczema cleared. Parallel to this, in vitro hyperreactivity to titanium
      disappeared. Although contact allergic reactions to titanium have been very
      rarely reported, these findings support a diagnosis of titanium allergy in our
      patient.

PMID- 16958917
TI  - Miconidin and miconidin methyl ether from Primula obconica Hance: new allergens
      in an old sensitizer.
AB  - Several chemical and clinical observations have suggested the presence of at
      least one more allergen in addition to primin in Primula obconica. The aim of
      this study was to investigate the allergenicity of the primin precursor miconidin
      and the related miconidin methyl ether, both isolated from P. obconica. 12 primin
      positive persons were patch tested with miconidin 0.01% petrolatum (pet.),
      miconidin in 96% ethanol incorporated into 0.01% pet., and miconidin methyl ether
      1.0% pet. All persons were positive to miconidin 0.01% pet., with the strength of
      reactions very similar to those of the individual primin reactions, and remained
      inexplicably negative while testing with miconidin in 96% ethanol and pet., while
      miconidin methyl ether elicited 7 positive reactions. Although both miconidin and
      miconidin methyl ether may be allergenic only due to their conversion to primin
      in the skin, the presence of these substances nevertheless has to be taken into
      account when assessing the allergenicity of new P. obconica cultivars.

PMID- 16958918
TI  - High-performance liquid chromatography analysis of rubber allergens in protective
      gloves used in health care.
AB  - A high-performance liquid chromatography (HPLC) method developed for analysis of
      zinc dithiocarbamates was validated and used to perform a survey of disposable
      medical gloves used in southern Sweden. The gloves were extracted with acetone at
      room temperature for 10 min by shaking. The extracts were injected into a
      polyether ether ketone lined HPLC column, and peaks were analysed by a diode
      array detector. The survey shows that of 19 gloves analysed, 10 contained zinc
      diethyldithiocarbamate (0.070-3.5 mg/g), 3 contained zinc
      pentamethylenedithiocarbamate (1.0-4.3 mg/g), 4 contained zinc
      dibutyldithiocarbamate (0.9-1.1 mg/g), and 2 contained 2-mercaptobenzothiazole
      (0.005-0.008 mg/g). None of them contained thiurams.

PMID- 16958919
TI  - Positive patch test reactions to allergens of the dental series and the relation
      to the clinical presentations.
AB  - The clinical manifestations of contact allergic dermatitis to dental materials
      are not uniform. This study was performed to detect the frequent allergens in the
      dental series associated with contact dermatitis and to define the causal
      relationship between the different allergens and the relevant clinical
      presentations. Between the years 2000 and 2004, 134 patients, aged 20-80 years,
      were patch tested. 121 patients were included in the study. The most frequent
      oral manifestations were cheilitis and perioral dermatitis (25.6%), burning mouth
      (15.7%), lichenoid reaction (14.0%), and orofacial granulomatosis (10.7%). 18
      (14.9%) patients were dental personnel, all of whom suffered from hand
      dermatitis. The common allergens detected included goldsodiumthiosulphate
      (14.0%), nickel sulfate (13.2%), mercury (9.9%), palladium chloride (7.4%),
      cobalt chloride (5.0%), and 2-hydroxyethyl methacrylate (5.8%). Positive
      reactions to metals were frequent in all the different clinical variants, and no
      specific association between a specific clinical presentation and a particular
      allergen was found. Allergy to mercury was not a significant factor contributing
      to the pathogenesis of oral lichenoid reactions. However, a strong association
      with contact allergy to mercury in dental fillings was found in 2 patients with
      orofacial granulomatosis.

PMID- 16958920
TI  - Contact allergy to (meth)acrylates in the dental series in southern Sweden:
      simultaneous positive patch test reaction patterns and possible screening
      allergens.
AB  - Contact allergy to dental allergens is a well-studied subject, more so among
      dental professionals than dental patients. 1632 subjects had been patch tested to
      either the dental patient series or dental personnel series at the department of
      Occupational and Environmental Dermatology, Malmo, Sweden. Positive patch tests
      to (meth)acrylate allergens were seen in 2.3% (30/1322) of the dental patients
      and 5.8% (18/310) of the dental personnel. The most common allergen for both
      groups was 2-hydroxyethyl methacrylate (2-HEMA), followed by ethyleneglycol
      dimethacrylate (EGDMA), triethyleneglycol dimethacrylate, and methyl
      methacrylate. 47 (29 dental patients and 18 dental personnel) out of these 48 had
      positive patch tests to 2-HEMA. All 30 subjects who had a positive reaction to
      EGDMA had a simultaneous positive reaction to 2-HEMA. One dental patient reacted
      only to 2,2-bis[4-(2-hydroxy-3-methacryloxypropoxy) phenyl]propane (bis-GMA).
      From our data, screening for (meth)acrylate contact allergy with 2-HEMA alone
      would have picked up 96.7% (29/30) of our (meth)acrylate-allergic dental patients
      and 100% (18/18) of our (meth)acrylate-allergic dental personnel. The addition of
      bis-GMA in dental patients would increase the pick-up rate to 100%.

PMID- 16958921
TI  - Preservatives sensitivity in Israel: a 10-year overview (1995-2004).
AB  - This study presents a 10-year survey of 2285 patients tested to common
      preservatives in northern Israel. The demographic and clinical data were analysed
      using a revised MOAHLFA index. Patch testing was based on the International
      Contact Dermatitis Research Group (ICDRG) guidelines. 411 (18%) patients were
      found to have positive reactions to 1 or more preservatives. The most frequent
      allergens tested positively were thimerosal,
      methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), and formaldehyde. The
      reactions to MCI/MI remained stable around 1.7% throughout the years 1995-1998,
      with a significant increase to 3.7%-4% (P = 0.029) during 1999-2004. The
      reactions to formaldehyde remained low around 0.3% until 1999; however, a
      considerable increase throughout the years 2000-2004 was noted, with rates of
      1.5%-1.9% (P = 0.028). The sensitivity rates for parabens, quaternium-15,
      imidazolidinylurea, and diazolidinylurea were low and unchanged, mostly under
      0.5%. As for methyldibromoglutaronitrile (MDBGN), sensitivity rates around 2%
      were detected for the years 1996 and throughout 2000-2004. Overall, this
      extensive survey showed a concerning increase in the sensitivity rates for
      MCI/MI, formaldehyde, and MDBGN.

PMID- 16958922
TI  - Hydroperoxides form specific antigens in contact allergy.
AB  - Concomitant positive reactions to colophonium, oxidized limonene, and/or oxidized
      linalool are recorded in patch test studies. The main allergens in these patch
      test mixtures are hydroperoxides, which form antigens by a radical pathway.
      Theoretically, concomitant reactions can be explained not only by concomitant
      sensitization or by true cross-reactions but also by the hydroperoxides acting as
      oxidizing agents on skin proteins to form non-specific antigens without hapten
      protein binding. The aim of this study was to explore concomitant reactions and
      cross-reactivity patterns among hydroperoxide haptens. We investigated whether
      individuals allergic to the main allergen in colophonium, 15-hydroperoxyabietic
      acid, would also react to limonene hydroperoxide or linalool hydroperoxide. Only
      1 of 29 individuals reacted to more than 1 hydroperoxide. The cross-reactivity
      pattern among cumene hydroperoxide, limonene hydroperoxide, 1-(1-hydroperoxy-1
      methylethyl) cyclohexene (cyclohexene hydroperoxide), and 15
      hydroperoxydehydroabietic acid was investigated in guinea-pigs. No general cross
      reactivity was observed. Cross-reactions between cumene hydroperoxide and
      cyclohexene hydroperoxide show that similarity in the overall structure and the
      way of antigen formation are needed. Quantum calculations were used to determine
      the formation energies of the intermediary radicals. We concluded that
      hydroperoxides form specific antigens and that formation of non-specific antigens
      is unlikely. The concomitant patch test reactions described in the literature are
      best explained as a result of multiple sensitizations.

PMID- 16958923
TI  - Intrinsic characteristics of contact and respiratory allergens influence
      production of polarizing cytokines by dendritic cells.
AB  - Type 1 and type 2 cytokines are primary mediators in contact allergy and
      aeroallergen-mediated disorders, respectively. For both types of disease,
      dendritic cells (DCs) are pivotal in initiating immune hyperresponsiveness. We
      studied whether contact and respiratory allergens possess intrinsic capacities to
      polarize DC towards DC1 and DC2 functions, independent of environmental factors.
      Human monocyte-derived DCs were exposed to the positive controls [type 1:
      lipopolysaccharide (LPS) + interferon-gamma; type 2: LPS + prostaglandin E(2)],
      contact allergens [2,4-dinitrochlorobenzene (DNCB), oxazolone (OXA), and nickel
      sulfate (NiSO(4))], and respiratory allergens [trimellitic anhydride (TMA) and
      the protein allergen derived from Dermatophagoides pteronyssinus (Der p1)]. The
      polarizing potentials of the allergens on DCs were determined by the secretion of
      type 1 [tumour necrosis factor-alpha (TNF-alpha), CXCL10, and interleukin (IL)
      12p70] and type 2 (IL-10) cytokines. The contact allergens, DNCB and OXA, induced
      strict type 1 DC polarization, whereas the respiratory allergens, TMA and Der p1,
      showed strict type 2 DC polarization. The contact allergen, NiSO(4), induced both
      DC1 (TNF-alpha and CXCL10 production) and DC2 (decreased IL-12p70/IL-10 ratio)
      features. These results support the view that allergens have an intrinsic
      capacity to skew immune responses at the DC level, irrespective of local factors
      such as those determined by cutaneous or mucosal epithelial microenvironments.

PMID- 16958924
TI  - Allergic contact dermatitis due to vitamin K1 contained in a cosmetic cream.

PMID- 16958925
TI  - Allergic contact dermatitis to prednicarbate presenting as lupus erythematosus.

PMID- 16958926
TI  - Eyelid dermatitis due to sodium metabisulfite.

PMID- 16958927
TI  - Occupational allergic contact dermatitis to N-isopropyl-N-phenyl-p
      phenylenediamine from a black rubber 'kidney' used in the ceramics industry.

PMID- 16958928
TI  - Allergic contact dermatitis from dioctyl maleate in a moisturizer.

PMID- 16958929
TI  - Occupational allergic contact dermatitis from olive oil.

PMID- 16958930
TI  - Moist toilet papers as possible sensitizers: review of the literature and
      evaluation of commercial products in Italy.

PMID- 16958931
TI  - Tetrahydracurcumin-related allergic contact dermatitis.

PMID- 16958932
TI  - 100 patients positive to balsam of Peru observed in Warsaw (Poland).

PMID- 16958933
TI  - Severe allergic hair dye reactions in 8 children.

PMID- 16958934
TI  - Unawareness in schizophrenia: neuropsychological and neuroanatomical findings.
AB  - The lack of insight in schizophrenia has so far been interpreted as a primary
      symptom of the illness, namely a defensive mechanism rather than a neurologically
      based condition. However, recent findings have emphasized its relationship with
      damage to specific brain areas as well as the domain specificity in which it may
      occur. This supports a neuropsychological interpretation of the lack of insight
      in schizophrenia. The present article reviews the foregoing data, and takes into
      account the most relevant anatomo-clinical results. There is evidence that the
      lack of insight in schizophrenia may occur as a neurological disease per se
      following brain damage that seems related to frontal lobe areas. Additionally, it
      could either be related to all aspects of the disease or be domain-specific,
      occurring for one kind of symptom but not for others. These data indicate several
      analogies with the phenomenon called anosognosia for a neurological deficit.

PMID- 16958935
TI  - Can personality traits help us explain disability in chronic schizophrenia?
AB  - Psychotic features have been considered the main determinant of psychosocial
      function in schizophrenia. However, other variables are likely to affect
      dysfunction in these patients. The authors' hypothesis is that personality traits
      in outpatients with chronic schizophrenia differ from traits found in the healthy
      population and may be associated with disability in this disorder. A total of 62
      patients with schizophrenia were evaluated with the Eysenck Personality
      Questionnaire (EPQ) and the Tridimensional Personality Questionnaire (TPQ).
      Psychotic features were measured with the help of the Positive and Negative
      Syndrome Scale (PANSS). Disability was assessed with the Disability Assessment
      Schedule (DAS). A total of 43 healthy subjects were used as controls for
      personality measurements. Normative data for the study population was also used
      to evaluate results in patients. Patients with schizophrenia had higher levels of
      neuroticism (median in percentile 65) and lower levels of extraversion (median in
      percentile 25) than the healthy population. Results of the TPQ showed higher harm
      avoidance and lower reward dependence levels compared to the healthy population.
      After multiple regression tests, negative symptoms were the strongest predictor
      of disability in patients with schizophrenia. Neuroticism contributed
      independently to the DAS overall behavior and global judgement subscales scores
      (more negative symptoms and higher neuroticism resulted in worse functioning),
      but not to the social role subscale. Outpatients with chronic schizophrenia
      showed high levels of neuroticism, harm avoidance, and introversion. Neuroticism
      significantly contributes to the long-term deficits found in patients with
      schizophrenia.

PMID- 16958936
TI  - Different dimensions of social support for the caregivers of patients with
      schizophrenia: main effect and stress-buffering models.
AB  - The aims of this study were: (i) to assess the impact of caring for patients with
      schizophrenia on the mental health status of the caregivers; and (ii) to examine
      the direct and buffer effects of social support on the mental health status of
      these caregivers. A total of 61 key caregivers of patients with schizophrenia
      were administered the Chinese Health Questionnaire (CHQ) and the Measure of
      Support Function (MSF) self-report questionnaire to assess their mental health
      and social support status. The MSF questionnaire constitutes four subscales,
      including: (i) the perceived crisis support (PCS); (ii) the perceived routine
      support (PRS); (iii) the received crisis support (RCS); and (iv) the received
      routine support (RRS) subscale. The Positive and Negative Syndrome Scale (PANSS)
      was used to assess the psychopathology severity of the patients they cared for.
      Then the authors used the hierarchical multiple regression model to analyze the
      relationship between these variables. The psychopathology severity of the
      patients reflected by the PANSS scores correlated inversely with the caregivers'
      CHQ scores. Besides, the PCS subscale scores correlated positively with the
      caregivers' CHQ scores. Moreover, the interaction between the RCS subscale scores
      and the PANSS scores was significant. Significant positive correlation between
      the RCS and CHQ exists only in the higher PANSS subgroup, but not in the lower
      PANSS subgroup. The psychopathological severity of the patients has a negative
      impact on their caregivers' mental health. PCS has a direct effect, and RCS has a
      buffer effect on the mental health status of these caregivers.

PMID- 16958937
TI  - Psychological and physical correlates of disordered eating in male and female
      Turkish college students.
AB  - The aim of this study was to examine the relationship between disordered eating
      and three psychological variables (obsessive and depressive symptoms, self
      esteem) and body mass index (BMI) in a sample of male and female college students
      in Turkey. Maudsley Obsessive-Compulsive Inventory (MOCI), Beck Depression
      Inventory (BDI), Rosenberg Self Esteem Scale (RSES), Eating Attitude Test (EAT),
      and Bulimic Investigatory Test, Edinburgh (BITE) scales were administered to 408
      college students (279 women; 129 men). By multiple regression analysis, the
      scales of MOCI, BDI, RSES and BMI were used as potential predictors of EAT and
      BITE scores for each gender. Obsessionality and BMI were the strongest predictors
      of bulimic and anorexic symptoms in women. In men, while the strongest predictors
      of bulimic symptoms were the depressive and obsessive symptoms, the best
      predictor of anorexic symptoms was obsession scores. There were significant
      differences and some similarities between male and female Turkish college
      students.

PMID- 16958938
TI  - Knowledge and attitude towards suicide among medical students in Japan:
      preliminary study.
AB  - Japan has one of the highest suicide rates in the world. Suicides numbered 32,863
      in 1998 and have exceeded 30,000 in every subsequent year. Education of those
      involved in general and psychosocial patient care can contribute greatly to
      suicide prevention. The authors administered a brief knowledge and attitude
      assessment questionnaire concerning suicide to students in their first, third,
      and fifth years at a Japanese medical school. Participants numbered 160 (94 men
      with a mean age of 21.8 years, SD = 3.01, and 66 women with a mean age of 21.2
      years, SD = 2.64); 59 first year, 52 third year, and 49 in their fifth year. The
      questionnaire consists of eight multiple-choice questions asking knowledge of
      suicide and one open-ended question asking attitude. In the knowledge part, only
      about half of the items were answered correctly (mean score was 4.21, SD = 1.28).
      A significant difference was observed in prevalence of attitudes as categorical
      variables between student years (P = 0.001). Sympathetic comments increased along
      with student years, while critical comments decreased. Given the frequent and
      interventional opportunities of primary-care medical contacts, poor understanding
      of suicide from the medical viewpoint was of concern. Moreover, judgmental
      attitudes were common, especially in earlier school years. Better informed, more
      understanding physicians and other health professionals could contribute greatly
      to prevention.

PMID- 16958939
TI  - Gender differences in psychiatric symptoms related to suicidal ideation in
      Japanese patients with depression.
AB  - Recent figures show that more than 30,000 people suicide each year in Japan, and
      that many of them are considered to suffer from depression. In addition, the
      suicide rate among Japanese women has been shown to be higher than in other
      countries. However, it is not clear whether the psychiatric symptoms leading to
      suicide differ by gender. The authors examined gender differences in psychiatric
      symptoms related to suicidal ideation (SI) in Japanese patients with depression.
      Study subjects were 199 new patients (66 men and 133 women) who were diagnosed
      with a major depressive disorder. SI and psychiatric symptoms were assessed by
      several psychological tests using questionnaires. Logistic regression analysis
      was used to calculate the odds ratio (OR) and 95% confidence interval (CI) with
      an adjustment for all relevant factors simultaneously. The stepwise method was
      also used for selecting variables. In univariate analysis, several psychosocial
      factors such as self-reproach, derealization, depressive moods,
      depersonalization, and anxiety traits were statistically significantly associated
      with SI in both men and women. However, multivariate analysis using the stepwise
      method distinguished gender differences. Low social/family support and
      depersonalization were statistically significantly associated with SI in men,
      while depressive moods and an anxiety state were significantly associated with SI
      in women. The relation between derealization and SI was statistically significant
      in women but not significant in men.

PMID- 16958940
TI  - Study of stress and vulnerability in patients with somatoform and dissociative
      disorders in a psychiatric clinic in North India.
AB  - The authors compared perceived stress in subgroups of patients defined by
      vulnerability (high and low) and disorder (somatoform and dissociative). A total
      of 30 patients each of somatoform and dissociative disorders diagnosed according
      to the classification of mental and behavioral disorders criteria were assessed
      with Presumptive Stressful Life Event Scale, The Hassles Scale, Psychoticism
      Extraversion Neuroticism Inventory, Dissociative Experience Scale, Twenty-Item
      Toronto Alexithyma Scale, and Illness Behavior Questionnaire. Somatoform and
      dissociative disorder groups had comparable scores on measures of perceived
      stress and vulnerability. Two-way anova showed significant main effect of
      neuroticism (F = 13.65, d.f. = 1.56, P < 0.01), psychoticism (F = 7.92, d.f. =
      1.56, P < 0.01), illness behavior (F = 5.82, d.f. = 1.56, P < 0.05), and
      dissociative experience (F = 8.45, d.f. = 1.56, P < 0.01) on total hassles score,
      but no significant main effect of disorder groups or interaction effect for
      disorder and vulnerability was seen on total hassles score. No significant main
      or interaction effect was seen on life events score. Similarities were seen in
      stress and vulnerability factors in the two disorders. Neuroticism, psychoticism,
      dissociative experience, and abnormal illness behavior were significantly related
      to stress (daily hassles) perceived by the patient, irrespective of the disorder.

PMID- 16958941
TI  - Relationships among mental health status, social context, and demographic
      characteristics in Taiwanese aboriginal adolescents: a structural equation model.
AB  - The purposes of this study were to examine the relationships among mental health
      status, demographic characteristics, and social contexts, including family
      conflict and support, connectedness to school, and affiliation with peers who
      exhibit delinquent behavior and who use substances, among Taiwanese aboriginal
      adolescents. A total of 251 aboriginal junior high school students in an isolated
      mountainous area of southern Taiwan were recruited, and the relationships among
      mental health status, demographic characteristics, and social contexts among them
      were examined using a structural equation model (SEM). The SEM revealed that
      family conflict and support had direct influences on mental health status and
      connectedness to school. Family conflict had a direct relationship with
      affiliation with peers who use substances, and family conflict and support were
      both indirectly linked with affiliation with peers who exhibit delinquent
      behavior and who used substances; these were mediated by a poor mental health
      status. Female and older age were directly linked with a poor mental health
      status and were indirectly linked with a greater number of peers who exhibit
      delinquent behavior and who use substances via the poor mental health status.
      Disruptive parenting was directly linked with affiliation with peers who use
      substances. The authors suggest that those who devise strategies to improve
      aboriginal adolescents' mental health and discourage substance use should take
      these relationships among mental health, demographic characteristics, and social
      contexts into account.

PMID- 16958942
TI  - Efficacy of milnacipran on cognitive dysfunction with post-stroke depression:
      preliminary open-label study.
AB  - The aim of this study was to assess the therapeutic efficacy of the serotonin
      norepinephrine reuptake inhibitor (SNRI), milnacipran, on both cognitive
      impairment and depression in post-stroke depression (PSD) patients. A total of 18
      PSD patients, approximately 3 months after stroke, were divided into two groups,
      milnacipran and control. A total of 10 patients were assigned to the milnaciprane
      group and eight were assigned to control group. Their cognitive impairment and
      mood symptoms were measured using the Mini-Mental State Examination (MMSE) and
      Hamilton Depression Rating Scale (HAM-D) both at the time of admission and at
      discharge, an interval of approximately 3 months. This study examined the changes
      in both MMSE and HAM-D scores during the study period. A significant time-by
      group interaction for results of the MMSE was observed, although there was no
      significant difference between the two groups on the HAM-D. Amelioration of
      cognitive impairment was greater in the milnacipran group than the control group.
      For PSD patients, milnacipran is effective in improving cognitive dysfunction.

PMID- 16958943
TI  - Direct effects of short-term psychoeducational intervention for relatives of
      patients with schizophrenia in Japan.
AB  - This study examined the direct effects of short-term psychoeducation on relatives
      of inpatients with schizophrenia, with the goal of introducing this type of
      support program into standard care. The subjects were 46 relatives of inpatients
      with schizophrenia who attended three or four sessions of psychoeducation. Levels
      of anxiety and subjective burden and distress were measured before and after
      sessions using self-administered rating scales. In addition, levels of expressed
      emotion were also measured. Results showed that both state and trait anxiety on
      the State-Trait Anxiety Inventory were significantly lower after
      psychoeducational intervention than before intervention. In addition, subjective
      burden and distress reported by the family significantly decreased on the
      subscales for family confusion resulting from a lack of knowledge of the illness
      and anxiety about the future, subjective burden and depression resulting from the
      patient's illness, and difficulties in the relatives' relationships with the
      patient. Comparison of high and low expressed emotion families showed that the
      intervention was almost equally effective for the two groups. However, its
      effectiveness with regard to the subjective burden and depression experienced by
      the families was significantly greater among high expressed emotion families. The
      present study confirmed that family psychoeducation during hospitalization, even
      for a short period, is effective for all families, whether high or low expressed
      emotion. Moreover, the results suggested that the intervention may have a greater
      effect on emotional factors in high expressed emotion families than in low
      expressed emotion families.

PMID- 16958944
TI  - Improvement of cognitive functioning in mood disorder patients with depressive
      symptomatic recovery during treatment: an exploratory analysis.
AB  - Depressive symptoms have a large impact on cognitive test performance of mood
      disorder patients. After remission, some improvement of cognitive functioning has
      been observed, but also stable deficits have been reported both during depression
      and remission. In the present study, the authors aimed to investigate the
      cognitive functioning of mood disorder patients in relation to early symptomatic
      recovery, by comparing performances at the Wechsler Adult Intelligence Scale
      Revised (WAIS-R) of responders and non-responders to the antidepressant
      treatment. The sample was composed of 51 hospitalized patients for a major
      depressive episode (major depressives/bipolars = 37/14). All patients were
      treated with fluvoxamine and evaluated at baseline and after 4 weeks using the 21
      item Hamilton Rating Scale for Depression. All subjects were once assessed for
      their cognitive functioning with the WAIS-R, at the end of the fourth week of
      treatment. In the current sample, patients who showed a significant symptomatic
      remission after 4 weeks of treatment showed higher total WAIS-R scores and a
      lower incidence of cognitive impairment, compared to non-responders to treatment.
      No major differences could be observed on any particular subtest, but rather a
      global improving of scores in responders compared to non-responders to
      pharmacotherapy. Pre-treatment illness severity, that was significantly higher
      among non-responders, was significantly associated with patients' intelligence
      quotient scores. Despite a number of limitations, present data support a strong
      effect of depressive symptoms on patients WAIS-R performances and an early global
      improvement of cognitive functioning concurrent with symptomathology recovery
      during pharmacological treatment.

PMID- 16958945
TI  - Clinical application of paroxetine for tapering benzodiazepine use in non-major
      depressive outpatients visiting an internal medicine clinic.
AB  - Chronic benzodiazepine (BDZ) users often have difficulty with BDZ withdrawal. To
      examine clinical effects of selective serotonin reuptake inhibitor (SSRI) on
      tapering BDZ use in non-depressive patients, 97 outpatients with a history of BDZ
      use for at least 3 months were recruited at an internal medicine clinic of a
      university hospital. After the 4th edition of the Diagnostic and Statistical
      Manual (DSM-IV) clinical interviews for screening major depression, 66
      outpatients (68%) without the DSM-IV major depression were randomly assigned to
      one of three groups: SSRI-assisted BDZ-reduction group (10-20 mg of paroxetine, n
      = 22), simple BDZ-reduction group (no paroxetine, n = 23), and reference group
      (no BDZ-reduction, n = 21). A standardized 8-week program involving gradual BDZ
      discontinuation was performed in the two BDZ-reduction groups. The Hamilton
      Rating Scales for Depression (HAM-D) and Anxiety (HAM-A) and the BDZ Withdrawal
      Symptom Questionnaire were assessed during the intervention period. Those with
      major depression were excluded from the BDZ-reduction intervention and treated
      with a different protocol of medication. In total, 10 (45.5%) in the SSRI
      assisted BDZ-reduction group (n = 22) succeeded in becoming BDZ-free after
      completing the program, whereas only four (17.4%) in the simple BDZ-reduction
      group (n = 23) succeeded. The assistance of the SSRI significantly predicted the
      success of becoming BDZ-free (P = 0.023), controlling for the effects of age,
      gender, period of BDZ use, and baseline HAM-D and HAM-A scores. The score changes
      on the three questionnaires were comparable (all P > 0.05) among the three groups
      during the intervention period. The use of SSRI may have beneficial effects on
      BDZ withdrawal without the worsening of mood states in cases without major
      depression.

PMID- 16958946
TI  - Clinical features of soft bipolarity in major depressive inpatients.
AB  - Because of the difficulties of ascertaining episode of hypomania by past history
      of the patients, it is of clinical value to find variables which predict the
      development of bipolar II disorder in depressive patients. Taking advantage of
      relatively long hospitalization, the authors tried to elucidate fine clinical
      features of the soft bipolarity. The subjects were 39 patients with Major
      Depressive Episode, diagnosed according to the 4th edition of the Diagnostic and
      Statistical Manual criteria. Among them, 15 patients were diagnosed as bipolar II
      disorder (BPII), whereas 24 patients were with unipolar depression (UP), using a
      structured clinical interview to assess the mood spectrum (SCI-MOODS). In
      addition to ordinary clinical and demographic variables, the authors studied fine
      symptomatology of depression, premorbid personality, and interpersonal
      relationship. Continuous variables were analyzed by t-test. Categorical variables
      were tested by chi2 analysis. In terms of premorbid personality, manic type
      (Zerssen) was found more frequently in BPII (UP 2/24, BPII 9/15, P < 0.05).
      Patients with BPII tended to show apparently quick disappearance of depressive
      symptoms (UP 2/24, BPII 9/15, P = 0.01). The most prominent result was a high
      prevalence of comorbidity of borderline personality disorder (BPD) among BPII (UP
      0/24, BPII 6/15, P = 0.02). As Akiskal indicated that mood lability represents
      the most powerful predictor of hypomanias, patients with BPII showed quick
      response in mood to admission. The current subjects with BPII had high frequency
      of manic type of premorbid personality, indicating the usefulness of this
      variable for the prediction of hypomanias. Finally, the authors could observe
      development of BPD during hospitalization exclusively among BPII, to support the
      possibility of BPD as a state effect of BPII.

PMID- 16958947
TI  - Combined cerebral blood flow effects of a cholinergic agonist (milameline) and a
      verbal recognition task in early Alzheimer's disease.
AB  - RU 35926/CI-979 (milameline) is a partial muscarinic agonist with promnestic
      effects in animal models. Preliminary animal studies suggest that this agent has
      the capacity to reverse cholinergic dysfunction and that it may impact on
      regional cerebral blood flow (rCBF). A total of 10 subjects with Alzheimer's
      disease (AD) of mild severity underwent high resolution split-dose single photon
      emission computed tomography (SPECT) during performance of a verbal recognition
      and control task, both before and after 18 weeks treatment with melameline or
      placebo. SPECT images were coregistered with individual's magnetic resonance
      imaging scans allowing extraction of rCBF values from multiple anatomical regions
      of interest (ROI). The effect of milameline was examined in eight individuals who
      were found after unblinding to be taking active drug. Effects of milameline were
      most apparent in the frontal regions, basal ganglia and thalamus. In the group as
      a whole, the greatest increase in rCBF due to milameline treatment was observed
      in the left globus pallidus. Response to milameline treatment was associated with
      increases in rCBF in the cingulate gyrus bilaterally, and less so for the left
      thalamus. Milameline-related increases in rCBF values were exaggerated by the
      verbal recognition task. Milameline has a demonstrable effect on cerebral blood
      flow in mild AD. Consistent with emerging animal data, the effects on rCBF appear
      most prominent in frontal and subcortical regions in AD subjects. The effects on
      rCBF appear to be augmented by the performance of a cognitively demanding task,
      raising the possibility that such tasks could assist in building an awareness of
      the functional neuropsychopharmacology of drugs designed for cognitive
      enhancement.

PMID- 16958948
TI  - Usher syndrome with psychotic symptoms: two cases in the same family.
AB  - Usher syndrome is a heterogeneous autosomal recessive disorder characterized by
      hearing and visual sensory impairment. Retinitis pigmentosa is essential for its
      diagnosis. There are only a few reports describing patients with Usher syndrome
      presenting with psychotic features and the etiology of its psychiatric
      manifestation is still unknown. Herein, the authors report variable congenital
      hearing impairment and progressive visual loss occurring in five of seven family
      members and two of them meeting the diagnostic criteria of Usher syndrome with
      psychotic features. Furthermore, the authors compare their psychiatric symptoms
      with other reports and the possible etiologies of psychotic symptoms are
      discussed.

PMID- 16958949
TI  - Recovery of cognitive function in neuropsychiatric Langerhan's cell
      histiocytosis.
AB  - Langerhan's cell histiocytosis (LCH) has been described as a progressive
      neurological disorder marked by neurological and cognitive decline. The authors
      here report a case of a childhood LCH sufferer who made a significant recovery of
      neuropsychological function in the absence of motor recovery in late adolescence.
      This differential recovery of motor and cognitive functioning may relate to the
      interaction between LCH and childhood and adolescent neurodevelopmental
      processes.

PMID- 16958950
TI  - Association study of a functional promoter polymorphism of the X-box binding
      protein 1 gene in Japanese patients with schizophrenia.
AB  - The functional promoter polymorphism -116C/G of the X-box binding protein 1
      (XBP1) gene was found to be associated with schizophrenia in Han Chinese and
      Japanese subjects, although contradictive negative findings were also reported in
      European populations. To confirm this association in a Japanese population, the
      authors conducted a case-control association study. There was no significant
      difference in both genotype and allele frequencies between the patients and
      control subjects, suggesting that the XBP1 -116C/G polymorphism might not confer
      increased susceptibility for schizophrenia in a Japanese population. However,
      further studies using a larger sample with detailed clinical data should be
      performed in several populations.

PMID- 16958951
TI  - Detecting malingering of Ganser-like symptoms with tests: a case study.
AB  - A middle-aged man presented with Ganser symptoms. He had been involved in a car
      crash and was seeking disability insurance benefits. Extensive testing with
      malinger instruments revealed that he performed below chance on simple memory
      tests and endorsed a variety of nonexistent symptoms. With this in mind, the
      authors collected collateral information which showed that the patient was
      involved in high level sports activities that were difficult to reconcile with
      the severe cognitive dysfunctions that he claimed to suffer from. The case
      demonstrates that Ganser-like symptoms deserve close scrutiny, preferably with
      malinger tests.

PMID- 16958952
TI  - Paranoid schizophrenia and idiopathic Parkinson's disease do coexist: a challenge
      for clinicians.

PMID- 16958953
TI  - Panic disorder and suicide in Mie Prefecture, Japan.

PMID- 16958954
TI  - Delirium and multiple electrolyte abnormalities associated with high dose
      paroxetine exposure.

PMID- 16958955
TI  - Acute stress symptoms in a victim of the Indian Ocean Tsunami.

PMID- 16958956
TI  - Raising the bar: a plea for standardization and quality improvement in the
      practice of breast pathology.

PMID- 16958957
TI  - Follow-up recommendations for benign breast biopsies.
AB  - Histologically proven benign breast disease increases a woman's relative risk for
      subsequent cancer development. Yet follow-up guidelines for mammogram and
      clinical breast examination after a benign breast biopsy are lacking. Our
      objective was to determine if increased surveillance is indicated following a
      benign breast biopsy. Following institutional review board approval, a
      retrospective database review was conducted of prospectively gathered patients
      who had a benign breast biopsy (core or excisional) for an abnormality detected
      on mammogram, ultrasound, or clinical breast examination. Follow-up, for all
      subjects, was a clinical breast examination and mammogram or ultrasound at 6
      months, 1 year, and 2 years after benign breast biopsy by a breast surgeon. End
      points were the need for additional biopsies or cancer detection. Statistical
      analysis was performed using chi-squared analysis. From January 2000 to July
      2003, 156 patients age 18-86 years had a benign breast biopsy. During the 2 year
      follow-up, 20 patients (13%) required a subsequent biopsy. No significant
      difference was observed in mean age, race, menarche, menopause, parity, age at
      first live birth, use of oral contraceptives, history of prior biopsy, or the
      pathology of the initial lesion between those who needed a subsequent biopsy and
      those who did not. Seven excisional biopsies were performed (one at 6 months,
      four at 1 year, and two at 2 years follow-up) for growth of the benign breast
      biopsy lesion, and pathology remained concordant with the original diagnosis.
      Thirteen biopsies were done for new findings on mammogram or ultrasound. Three of
      these (1.9%) yielded a cancer diagnosis (one at 6 months, one at 1 year, and one
      at 2 years follow-up). No new lesions were identified on follow-up by clinical
      breast examination alone. Increased surveillance following a benign breast biopsy
      is necessary because of the increased need for subsequent biopsy or risk of
      cancer development. This should include imaging (mammography or ultrasound) and a
      clinical breast examination 6 months, 1 year, and 2 years after a benign breast
      biopsy.

PMID- 16958958
TI  - Outcome of men presenting with clinical breast problems: the role of mammography
      and ultrasound.
AB  - The purpose of this study was to determine the outcome of men presenting with
      clinical breast problems for breast imaging and to evaluate the role of
      mammography and ultrasound in the diagnosis of benign and malignant breast
      problems. We retrospectively reviewed clinical, radiographic, and pathologic
      records of 165 consecutive symptomatic men presenting to Breast Imaging over a 4
      year period. We assessed the clinical indication for referral, mammographic
      findings, sonographic findings, histologic results, and clinical outcomes.
      Patients ranged in age from 22 to 96 years. Breast Imaging Reporting and Data
      System (BI-RADS) category 4 and 5 mammograms and solid sonographic masses were
      considered suspicious for malignancy. Six of 165 men (4%) had primary breast
      carcinoma, which were mammographically suspicious in all 6 (100%). Five were
      invasive ductal carcinoma and one was ductal carcinoma in situ (DCIS). Of 164
      mammograms, 20 (12%) were suspicious. Six were cancer and 14 were benign.
      Clinical follow-up for 2 years or biopsy results were available for 138 of the
      165 men (84%). Twelve with benign mammographic findings had benign biopsies. All
      men with benign mammography not undergoing biopsy were cancer free. Sensitivity
      for cancer detection (mammography) was 100% and specificity was 90%. Positive
      predictive value (mammography) was 32% (6 of 19) and the negative predictive
      value was 100%. Sonography was performed in 68 of the 165 men (41%). Three of
      three cancers (100%) were solid sonographic masses. There were 9 of 68 false
      positive examinations (13%). Sensitivity and negative predictive value for cancer
      detection (ultrasound) was 100% and specificity was 74%. The most common clinical
      indication for referral was mass/thickening (56%). Mammography had excellent
      sensitivity and specificity for breast cancer detection and should be included as
      the initial imaging examination of men with clinical breast problems. The
      negative predictive value of 100% for mammography suggests that mammograms read
      as normal or negative need no further examination if the clinical findings are
      not suspicious. A normal ultrasound in these men confirms the negative predictive
      value of a normal mammogram.

PMID- 16958959
TI  - Preoperative lymphatic mapping does not predict the number of axillary sentinel
      lymph nodes identified during surgery in breast cancer patients.
AB  - Sentinel lymph node biopsy (SLNB) has become the standard of care in most centers
      for axillary staging in patients with early breast cancer. Multiple radioactive
      nodes are often identified at surgery. The finding of multiple sentinel lymph
      nodes (SLNs) has been shown to be associated with lower rates of false-negative
      results in the SLNB procedure, hence the importance of removing and examining all
      SLNs. Often preoperative lymphatic mapping (PLM) is performed prior to surgery.
      In this study we examined whether the exact number of SLNs identified during
      surgery can be accurately predicted by PLM. During the years 2001-2004, 155
      patients underwent both PLM and a SLNB in our breast unit. During surgery, an
      attempt was made to remove all radioactive nodes. The number of axillary
      radioactive foci found on PLM was compared with the number of radioactive nodes
      identified during surgery. The average number of sentinel nodes harvested was 2.3
      (range 1-9). The average number of radioactive foci identified on PLM was 1.8
      (range 0-5). Of the 155 patients, the number of sentinel nodes retrieved in
      surgery was greater than that found in preoperative mapping in 65 patients
      (41.9%), equal to that found in preoperative mapping in 60 patients (38.7%), and
      less than that found in preoperative mapping in 30 patients (19.4%). Thus in most
      patients, the number of SLNs found on PLM did not reflect the number of SLNs
      found intraoperatively. Therefore, even when the number of nodes identified on
      PLM has been reached in surgery, a meticulous search for additional nodes should
      still be carried out. The number of hot spots in preoperative mapping should
      serve as a rough indicator of the smallest number of nodes the surgeon should
      attempt to resect, but not the exact number of nodes expected to be found.

PMID- 16958960
TI  - Can methylene blue only be used in sentinel lymph node biopsy for breast cancer?
AB  - Sentinel lymph node biopsy (SLNB) has become an accepted standard of care to
      stage the axilla for clinically node-negative early stage breast cancer. In
      experienced hands, studies have shown an acceptable rate of identification of the
      sentinel lymph node (SLN) with blue dye only. Lymphazurin is occasionally
      associated with severe allergic reaction, including anaphylaxis and death. The
      use of methylene blue alone as a method of identifying the SLN in breast cancer
      has been reported once previously in the literature. Methylene blue may be an
      acceptable alternative with fewer deleterious side effects. Medical records of
      patients, who underwent sentinel node mapping between September 2003 and March
      2005 by two surgeons at an academic medical center were reviewed. SLN mapping was
      performed by periareolar injection of 5 cc of 1% methylene blue. All patients
      with positive SLNs underwent completion axillary node dissection. During the
      study period, 141 consecutive patients with clinically node-negative axillas and
      without evidence of inflammatory breast cancer underwent SLNB with injection of
      methylene blue only. A SLN was identified in 136 of 141 patients (96.5%). Thirty
      three of 136 SLNs (24%) harbored metastatic disease. No cases of anaphylaxis were
      noted. In experienced hands, methylene blue alone is a highly sensitive method of
      detecting SLNs. Avoiding the greater frequency of allergic reactions seen with
      lymphazurin is an important advantage of methylene blue.

PMID- 16958961
TI  - The impact of HER-2 status on local recurrence in women with stage I-II breast
      cancer treated with breast-conserving therapy.
AB  - This study was undertaken to determine whether overexpression of the oncogene HER
      2 is associated with an increase in local recurrence in women with early stage
      breast cancer treated with breast-conserving therapy (BCT). A retrospective
      review of the medical records of all women treated with stage I-II invasive
      breast cancer from 1991 through 2001 was performed. Of 596 eligible patients
      treated in that time period, immunohistochemical testing for HER-2 expression was
      performed in 352 patients (59%): 266 patients (76%) were HER-2 negative and 86
      patients (24%) were HER-2 positive. Median follow-up was 5.4 years. The patient
      characteristics for the two groups were compared for age, pathologic T and N
      stage, number of positive nodes, estrogen receptor (ER) and progesterone receptor
      (PR) status, radiation treatment, and use of hormonal therapy or chemotherapy.
      There were no significant differences in any of these parameters between the two
      groups (all p > or = 0.10). Local recurrence at 5 years was 2% in the HER-2
      negative group and 0% in the HER-2-positive group (p = 0.15). There was no
      difference in local recurrence after BCT between HER-2-positive and negative
      breast cancers at 5 years. Therefore HER-2 overexpression does not appear to be a
      contraindication to BCT.

PMID- 16958962
TI  - Gastrointestinal carcinomas occurring in breast cancer patients.
AB  - Breast cancer patients are reported to have a higher rate of second primary
      malignancies. We retrospectively reviewed the coexistence of breast and
      gastrointestinal (GI) tumors in the same patients and the characteristics of the
      tumors. The charts of all patients more than 35 years of age who were diagnosed
      with breast cancer and hospitalized for various reasons between 1985 and 2003
      were reviewed and those who also had a diagnosis of GI malignancy were then
      selected. Age and tumor characteristics were evaluated. Out of all the patients,
      2,650 had a diagnosis of breast cancer, while 40 (1.5%) also had GI malignancies.
      Among a comparable group of 70,784 consecutive female patients without breast
      cancer, 1,292 patients (1.8%) had a diagnosis of GI malignancy. The location of
      GI tumors in patients with both tumors was as follows: stomach, 6 (15%); right
      colon, 8 (20%); left colon, 7 (17.5%); sigma, 9 (22.5%); and rectum, 10 (25%).
      Seventeen of the patients (51.5%) had Dukes C and D tumors, 14 (42.5%) Dukes B,
      and 2 (6%) Dukes A or in situ. The stage of the others was not identified. The
      mean age at diagnosis of breast cancer was 68.5 years (range 48-88 years). In 23
      (57.5%), GI cancer was diagnosed after breast cancer, in 7 (17.5%) it was
      diagnosed within 3 months of diagnosing breast cancer, and in 8 (20%) it was
      diagnosed prior to the diagnosis of breast cancer. Five patients suffered from an
      additional primary cancer: three endometrial, one lung, one esophageal, and one
      patient had two additional tumors in the endometrium and thyroid. We conclude
      that the rate of GI malignancies in breast cancer patients is slightly lower than
      in comparable patients without breast cancer. GI malignancies tend to be
      diagnosed later and are found more often in the distal colon.

PMID- 16958963
TI  - Seroma prevention using Mytilus edulis protein in a rat mastectomy model.
AB  - Seroma formation is common following mastectomy and autologous breast
      reconstruction and is a potential cause of significant morbidity in patients. For
      this reason, many methods have been investigated to prevent this complication. BD
      Cell-Tak is a tissue adhesive formulated from the proteins excreted by the marine
      mussel Mytilus edulis. The purpose of this study was to determine if Cell-Tak is
      able to prevent seroma formation in a rat mastectomy seroma model. Twenty Sprague
      Dawley rats underwent unilateral radical mastectomy, partial axillary lymph node
      dissection, and disruption of the dermal lymphatics. The animals were randomly
      assigned to either control (n = 10) or experimental groups (n = 10). The
      experimental animals received 0.3 ml of the topical adhesive in the wound prior
      to closure, whereas control animals received no treatment. On postoperative day
      7, seroma collections were aspirated and quantified and the tissue flaps were
      sent for histologic analysis. The control rats had a mean seroma volume of 5.3 +/
      2.6 ml, whereas the rats treated with Cell-Tak tissue adhesive had a mean seroma
      volume of 1.8 +/- 1.5 ml (p < 0.004). Histologic analysis revealed mild
      inflammation consistent with postoperative changes in both groups and no evidence
      of foreign body reaction to the adhesive. BD Cell-Tak tissue adhesive
      significantly reduces seroma formation in the rat mastectomy model. This tissue
      adhesive may prove beneficial in patients undergoing mastectomy with or without
      breast reconstruction.

PMID- 16958964
TI  - Predicting compliance in a breast cancer prevention trial.
AB  - The impact of chemoprevention trials can be hampered by poor participant
      compliance with the study medication. We used medication monitoring systems and
      pill count data to try to establish factors that may predict compliance with the
      International Breast Intervention Study (IBIS) and whether the participants went
      on to complete or benefit the trial. Women who took their trial medication in a
      regular pattern rather than randomly were more likely to be of benefit to the
      study (p = 0.003). For those women who failed to complete the study, compliance
      was shown to gradually reduce at each follow-up appointment. The taking of
      additional prescribed medication and not smoking were important factors in
      predicting completion (p = 0.04 and p = 0.047, respectively) and benefit (p =
      0.037 and p = 0.031, respectively) to the study. Taking these factors into
      account when advising women at the start of a chemoprevention trial may be
      helpful in improving compliance.

PMID- 16958965
TI  - Breast asymmetry: presentation of a giant fibroadenoma.
AB  - Patients often present to plastic surgeons with breast asymmetry of unknown
      etiology. Many patients are females in late adolescence and present complaining
      of a hypoplastic breast on the smaller side. However, full evaluation may reveal
      that the larger breast contains the abnormality. Fibroadenomas typically present
      as firm, mobile, painless, easily palpable breast nodules. However, giant
      fibroadenomas can present as unilateral macromastia without definable borders or
      texture differences. Diagnosis is essential since fibroadenomas tend to persist
      and grow. However, physical examination and standard radiographic evaluations
      (mammograms and ultrasounds) fail to clarify the diagnosis in many cases.
      Magnetic resonance imaging (MRI) has improved preoperative diagnosis, but tissue
      diagnosis is frequently necessary and resection of giant fibroadenomas is
      essential as they enlarge to the point of causing psychological detriment or mass
      effects, including venous congestion, glandular distortion, pressure necrosis,
      and occasionally ulceration. In this article we review nine patients presenting
      with unilateral macromastia to a tertiary breast care center with a review of the
      pertinent literature. The differential diagnosis, evaluation modalities, and
      treatment options of breast asymmetry and unilateral breast masses are presented.
      Postexcision breast reconstruction is discussed.

PMID- 16958966
TI  - Anthropometry and breast cancer risk in Nigerian women.
AB  - The recent upsurge in global obesity and the recognition of the role of metabolic
      syndrome and other correlates of obesity in the etiology of breast cancer and
      other chronic diseases has created the impetus for renewed interest in the role
      of anthropometric measures in breast cancer risk. This case-control study was
      designed to evaluate the role of anthropometric variables in breast cancer
      susceptibility in an indigenous sub-Saharan African population drawn from
      midwestern and southeastern Nigeria, a population grossly underreported in the
      global epidemiologic literature. Study participants were 250 women with breast
      cancer who were receiving treatment in the surgical outpatient clinics and
      surgical wards of four university teaching hospitals located in midwestern and
      southeastern Nigeria, while the controls were 250 age-matched women without
      breast cancer or other malignant diseases being treated for other surgical
      diseases in the same institutions between September 2002 and April 2004.
      Waist:hip ratio (WHR) was associated with a significant 2.5-fold increased risk
      of premenopausal breast cancer (odds ratio [OR] = 2.56, 95% confidence interval
      [CI] 1.48-4.41] and a 2-fold increased risk of postmenopausal breast cancer (OR =
      2.00, 95% CI 1.04-2.53). Increasing height conferred a modestly nonsignificant
      increased risk of premenopausal breast cancer (OR = 1.59, 95% CI 0.98-2.58). The
      study showed that WHR is a significant predictor of breast cancer risk in
      Nigerian women and measures to sustain increased physical activity and ensure
      healthy dietary practices are recommended to reduce the burden of obesity in the
      population.

PMID- 16958967
TI  - Phleboliths detected on mammography.
AB  - Phleboliths are commonly found on conventional radiographs of the pelvis.
      However, phleboliths detected on mammography are extremely rare. We report one
      case of phleboliths detected on mammography that were in varicosities adjacent to
      a venous aneurysm.

PMID- 16958968
TI  - Multicentric glioblastoma multiforme in a patient with BRCA-1 invasive breast
      cancer.
AB  - Breast cancer is the most common cancer in women. Germline mutations in BRCA-1
      and BRCA-2 significantly increase the risk of developing breast and ovarian
      cancers, and are also associated with an increased incidence of primary cancers
      at other sites. We report the case of a 46-year-old woman previously treated for
      ductal adenocarcinoma of the breast with BRCA-1 who subsequently was diagnosed
      with multicentric glioblastoma multiforme (GBM) in the right temporal and right
      occipital lobes. We briefly discuss the incidence of BRCA-1 mutations in breast
      cancer as well as other primary neoplasms and consider potential mechanisms
      shared in the pathogenesis of breast and glial tumors.

PMID- 16958969
TI  - Objective clinical regression of metastatic breast cancer in disparate sites
      after use of whole-cell vaccine genetically modified to release sargramostim.
AB  - A patient with recurrent breast cancer metastases following initial response to
      chemotherapy and hormonal maintenance was treated with a whole-cell tumor
      vaccine, resulting in a prompt objective complete remission of a lung lesion on
      computed tomography (CT) scans and near-complete regression of multiple breast
      lesions on magnetic resonance imaging (MRI). Three months after completion of the
      protocol, metastases were again found in the breast and lung, with new lesions in
      the brain and liver. Reinstitution of vaccine inoculation resulted in major
      regression of the brain and breast lesions, improvement in all other areas, and
      no indication of new lesions. Therapy consisted of inoculation of 20 x 10(6) SV
      BR-1-GM cells, a unique breast cancer cell line transfected to release
      sargramostim (granulocyte macrophage colony-stimulating factor [GM-CSF]).
      Following lethal irradiation to 200 cGy, vaccine was injected intradermally in
      four divided doses to the back and thighs, every 2 weeks x 3, then every month x
      3. Each treatment was preceded 48 hours earlier with low-dose cyclophosphamide
      300 mg/m2 to abrogate regulatory T-cell activity. Interferon (IFN)-alpha, 20,000
      IU, was injected into each inoculation site at 48 and 96 hours postinoculation to
      provide an additional "danger signal." The patient developed positive delayed
      type hypersensitivity responses and also antibody reactivity to the vaccine
      cells.

PMID- 16958970
TI  - Transverse rectus abdominis myocutaneous flap wound-healing complications in
      breast reconstruction: assisted closure using foam suction dressing.
AB  - Transverse rectus abdominis myocutaneous (TRAM) flap necrosis is a difficult
      reconstructive problem which historically has entailed protracted management with
      poor aesthetic outcome. The use of a foam suction dressing achieves effective
      delayed primary closure of the flap wound with an acceptable aesthetic result.
      The results of using a vacuum-assisted closure (VAC) system were examined in
      three patients. The VAC system was found to be safe and effective in facilitating
      the closure of large and complex wounds without skin grafting. This option should
      thus be given serious consideration in some difficult wound healing situations.

PMID- 16958971
TI  - Left breast necrosis following cardiac bypass surgery.
AB  - The following is a case report of left breast necrosis following coronary artery
      bypass grafting (CABG) in a woman previously treated for a stage I breast
      carcinoma. To our knowledge this is the first such report of its kind in the
      literature. We believe that breast tumor extirpation and internal mammary artery
      utilization in combination are not sufficient insults on the vascularity of the
      breast to account for necrosis, but rather we feel that a variety of conditions
      are necessary for vascular compromise to occur.

PMID- 16958972
TI  - Musculus sternalis: a normal but rare mammographic finding and magnetic resonance
      imaging demonstration.

PMID- 16958973
TI  - Choroidal metastasis in a patient with disseminated breast cancer: hormonal
      therapy-induced regression.

PMID- 16958974
TI  - Routine mammographic imaging: it was only a needle.

PMID- 16958975
TI  - Granular cell (Abrikossof) tumor of the breast.

PMID- 16958976
TI  - Pregnancy-induced gigantomastia in a 19-year-old woman.

PMID- 16958977
TI  - Why adjuvant trastuzumab led to better outcomes in women with high-risk HER-2
      positive breast cancer.

PMID- 16958978
TI  - High prevalence of HER-2/neu overexpression among Iranian women with breast
      cancer: true or false?

PMID- 16958979
TI  - Talc seromadesis: a novel technique for the treatment of chronic seromas
      following breast surgery.

PMID- 16958980
TI  - E-mail and the breast surgeon: a survey of the membership of the American Society
      of Breast Surgeons.

PMID- 16958981
TI  - Aromatase inhibitors in premenopausal women: the need for proper contraceptive
      counseling.

PMID- 16958982
TI  - Abstracts from the AABB Annual Meeting, Miami Beach, Florida, USA, October 21-24,
      2006.

PMID- 16958983
TI  - Efficacy of rimonabant and other cannabinoid CB1 receptor antagonists in reducing
      food intake and body weight: preclinical and clinical data.
AB  - The present paper focuses on the different lines of evidence indicating that
      cannabinoid CB(1) receptor antagonists, including the prototype rimonabant,
      reduce food intake and body weight in laboratory animals. Recent clinical surveys
      demonstrated that rimonabant significantly reduced body weight also in
      overweight/obese humans. Treatment with rimonabant was associated with a
      beneficial effect on different metabolic parameters and cardiovascular risk
      factors linked to overweight. The data reviewed in this paper suggest that
      cannabinoid CB(1) receptor antagonists may constitute a novel class of drugs
      potentially effective in the treatment of obesity-related disorders.

PMID- 16958984
TI  - A-85380: a pharmacological probe for the preclinical and clinical investigation
      of the alphabeta neuronal nicotinic acetylcholine receptor.
AB  - A-85380 [3-(2(s)-azetidinylmethoxy) pyridine] is a neuronal nicotinic
      acetylcholine receptor (nAChR) agonist that has been a useful tool in the
      investigation of the function of nAChRs in both preclinical and clinical studies.
      Amongst nAChR subtypes, A-85380 shows selectivity for the alpha(4)beta(2) vs. the
      alpha(7) or alpha(1)beta(1)deltagamma nAChRs. In functional in vitro cation flux
      assays, A-85380 is a potent and full agonist. A-85380 has a broad-spectrum
      analgesic profile with efficacy in acute, persistent, and neuropathic pain
      models. As demonstrated using selective nAChR antagonists or alpha(4) antisense,
      the alpha(4)beta(2) nAChR mediates the analgesic effects of A-85380.
      Interestingly, the site of action depends upon the type of pain as
      antinociception is mediated by descending inhibition into the spinal cord whereas
      anti-allodynia in neuropathic pain is mediated at both central and peripheral
      sites. Radiolabelled forms of A-85380 have been developed and shown to be safe
      for use in vivo in humans. In clinical studies using positron and photon emission
      tomography, marked decreases in alpha(4)beta(2) nAChRs have been seen in patients
      with Parkinson's and Alzheimer's disease. Although not developed as a therapeutic
      agent, A-85380 has proven to be an important component in the development of
      novel nAChR ligands for the treatment of pain and other disorders.

PMID- 16958985
TI  - Humanin and colivelin: neuronal-death-suppressing peptides for Alzheimer's
      disease and amyotrophic lateral sclerosis.
AB  - Humanin (HN), a 24-amino-acid neuroprotective peptide, was originally found in
      the occipital lobe of an autopsied Alzheimer's disease (AD) patient. HN inhibits
      neuronal death by binding to its specific receptor on the cell membrane and
      triggering a Jak2/STAT3 prosurvival pathway. The activation of this pathway may
      represent a therapeutic approach to AD. HN also exhibits neuroprotective activity
      against toxicity by familial amyotrophic lateral sclerosis (ALS)-related mutant
      superoxide dismutase (SOD1). Recent investigations established that AGA-(C8R)
      HNG17, a 17-amno-acid derivative of HN, is 10(5) times more potent as a
      neuroprotective than HN; at 10-picomolar and higher concentrations in vitro it
      completely suppresses neuronal death. Moreover, a 26-amino-acid peptide colivelin
      (CL), composed of activity-dependent neurotrophic factor (ADNF) C-terminally
      fused to AGA-(C8R)-HNG17, provides complete neuroprotection at 100-femtomolar or
      higher concentrations in vitro. A series of experiments using mouse AD and ALS
      models further established the efficacy of HN derivatives, including CL, against
      these diseases in vivo. HN and CL can be viewed as drug candidates for neuronal
      death suppression therapy in AD or ALS.

PMID- 16958986
TI  - Preclinical and clinical pharmacology of DOV 216,303, a "triple" reuptake
      inhibitor.
AB  - DOV 216,303 [(+/-)-1-(3,4-dichlorophenyl)-3-azabicyclo-[3.1.0]hexane
      hydrochloride] is the prototype of a class of compounds referred to as "triple"
      reuptake inhibitors. Such compounds inhibit the reuptake of norepinephrine (NE),
      serotonin (5-HT), and dopamine (DA), the three neurotransmitters most closely
      linked to major depressive disorder. DOV 216,303 inhibits [(3)H]NE, [(3)H]5-HT,
      and [(3)H]DA uptake to the corresponding human recombinant transporters
      (expressed in HEK 293 cells) with IC(50) values of approximately 20, 14, and 78
      nM, respectively. DOV 216,303 is active in tests predictive of antidepressant
      activity including the mouse forced swim test and reversal of tetrabenazine
      induced ptosis and locomotor depression. The pharmacodynamic, pharmacokinetic,
      and toxicological profile of DOV 216,303 in animals prompted us to initiate
      clinical studies. In both single and multiple dose studies using normal
      volunteers, DOV 216,303 was safe and well-tolerated. Furthermore, both C(max) and
      AUC values were dose-proportional between 5-150 mg. The plasma concentrations of
      DOV 216,303 at doses >10 mg were in excess of the IC(50) values for inhibition of
      biogenic amine reuptake. In a Phase II study designed to explore the safety and
      tolerability of DOV 216,303 in depressed individuals, patients received either
      100 mg DOV 216,303 (50 mg b.i.d.) or 40 mg citalopram (20 mg, b.i.d.) for two
      weeks. A placebo arm was not employed in this study because several institutional
      review boards required administration of an active control to severely depressed
      individuals. Time dependent reductions in HAM-D scores (the primary outcome
      measure) were observed in both the DOV 216,303 and citalopram groups compared to
      baseline scores (p < 0.0001). The side effect profile was not remarkably
      different between treatment arms. These findings provide preliminary evidence of
      a clinically meaningful antidepressant action with a molecule capable of
      inhibiting the three transmitters most closely linked to major depressive
      disorder.

PMID- 16958987
TI  - Involvement of calpain activation in neurodegenerative processes.
AB  - One of the challenges in the coming years will be to better understand the
      mechanisms of neuronal cell death with the objective of developing adequate drugs
      for the treatment of neurodegenerative disorders. Caspases and calpains are among
      the best-characterized cysteine proteases activated in brain disorders. Likewise,
      during the last decade, extensive research revealed that the deregulation of
      calpains activity is a key cytotoxic event in a variety of neurodegenerative
      disorders. Moreover, interest in the role of calpain in neurodegenerative
      processes is growing due to implication of the involvement of cdk5 in
      neurodegenerative diseases. Since calpain inhibitors appear to not only protect
      brain tissue from ischemia, but also to prevent neurotoxicity caused by such
      neurotoxins as beta-amyloid or 3-nitropropionic acid, the currently available
      data suggest that calpain and cdk5 play a key role in neuronal cell death. It
      seems clear that the inappropriate activation of cysteine proteases occurs not
      only during neuronal cell death, but may also contribute to brain pathology in
      ischemia and traumatic brain disorders. Pharmacological modulation of calpain
      activation may, therefore, be useful in the treatment of neurodegenerative
      disorders. It is possible, although difficult, to develop synthetic inhibitors of
      cysteine proteases, specifically calpains. The inhibition of calpain activation
      has recently emerged as a potential therapeutic target for the treatment of
      neurodegenerative diseases.

PMID- 16958988
TI  - Metabotropic glutamate receptor subtype 5 antagonists MPEP and MTEP.
AB  - Glutamate regulates the function of central nervous system (CNS), in part,
      through the cAMP and/or IP3/DAG second messenger-associated metabotropic
      glutamate receptors (mGluRs). The mGluR5 antagonist 2-methyl-6-(phenylethynyl)
      pyridine (MPEP) has been extensively used to elucidate potential physiological
      and pathophysiological functions of mGluR5. Unfortunately, recent evidence
      indicates significant non-specific actions of MPEP, including inhibition of NMDA
      receptors. In contrast, in vivo and in vitro characterization of the newer mGluR5
      antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) indicates that
      it is more highly selective for mGluR5 over mGluR1, has no effect on other mGluR
      subtypes, and has fewer off-target effects than MPEP. This article reviews
      literature on both of these mGluR5 antagonists, which suggests their possible
      utility in neurodegeneration, addiction, anxiety and pain management.

PMID- 16958989
TI  - An invitation to join the World Society of Breast Health.

PMID- 16958990
TI  - Complementary credit and trust: the only, but narrow path to worldwide optimal
      breast care.

PMID- 16958991
TI  - Toward optimized breast cancer care with East/West-linked wisdom.

PMID- 16958992
TI  - Paradigm shift of staging and treatment for early breast cancer in the sentinel
      lymph node era.
AB  - Lymph node status is the most reliable prognostic indicator for the clinical
      outcome of patients with most solid cancers. Because it is the first node
      draining the primary cancer, the sentinel lymph node (SLN) is most likely to
      harbor metastatic cancer cells. The tumor size of primary breast cancer is highly
      correlated with SLN metastasis. If the SLN is negative, the negative predictive
      value of the remaining nodal basin exceeds 95%. It appears that even using
      different techniques from different institutions, the successful rate to harvest
      the SLN is more than 95%. The false-negative rate is about 5-10% in most series.
      Breast cancer patients with early detection and a negative SLN have a
      significantly improved survival rate. The SLN data in breast cancer is so
      convincing that SLN information has been incorporated into the new American Joint
      Committee on Cancer (AJCC) classification of breast cancer. The therapeutic value
      of additional lymph node dissection after a positive SLN for breast cancer is
      still controversial. Follow-up data from breast cancer patients is somewhat
      limited, but available information shows that patients with negative SLNs fare
      much better. In summary, several important patterns of metastasis can be
      established based on the current SLN experience: 1) The earlier the breast cancer
      is found, the less the metastatic potential. 2) In most cases, breast cancer
      follows an orderly progression of metastasis to the SLN. 3) A small subgroup of
      patients may develop systemic dissemination without SLN involvement. Since
      metastatic cancer is usually incurable, it is important for oncologists to detect
      and resect an early breast cancer without delay. The challenge in the future will
      be to dissect these different patterns of metastasis based on molecular or
      genetic markers. Such information will be critical to select high-risk patients
      for adjuvant therapy.

PMID- 16958993
TI  - Sentinel lymph node biopsy for breast cancer: current controversies.
AB  - Sentinel lymph node biopsy (SLNB) has replaced the routine level I and II
      axillary lymph node dissection (ALND) for women with clinically node-negative T1
      and T2 breast cancer. Studies have shown that SLNB is highly predictive of
      axillary nodal status with a false-negative of rate less than 10%. Our purpose
      was to address some of the ongoing controversies about this procedure, including
      technical issues, use of preoperative lymphoscintigraphy, internal mammary lymph
      node biopsy, criteria for patient selection (in intraductal carcinoma?), its
      staging accuracy, and the clinical approach when a SLNB was found to be negative
      or positive on pathologic examination. After the revision of the American Joint
      Committee on Cancer (AJCC) staging system for breast cancer in 2002, the
      evaluation of internal mammary lymph nodes and determination of micrometastases
      by hematoxylin-eosin or by immunohistochemistry have become increasingly
      important in staging of patients. Recent guideline recommendations developed by
      the American Society of Clinical Oncology (ASCO) Expert Panel in 2005 are also
      discussed. Long-term follow-up results of ongoing studies will provide more
      accurate assessment of the prognostic significance of SLNB and its value in the
      prevention of breast cancer-related morbidity in axillary staging compared to
      ALND.

PMID- 16958994
TI  - Pathologic examination of the sentinel lymph node: what is the best method?
AB  - Sentinel lymph node biopsy (SLNB) has become an acceptable alternative to
      complete axillary dissection to determine whether breast cancer has spread to
      axillary lymph nodes. Yet the best method for pathologic examination of the
      sentinel lymph node (SLN) remains controversial. For years there has been
      speculation that micrometastases in axillary lymph nodes were clinically
      insignificant and thus lymph nodes did not require sectioning at close intervals.
      Yet essentially all studies, including a recent large prospective study, have
      found a significantly poorer prognosis associated even with metastases less than
      2 mm in size-the most common definition of micrometastasis-suggesting that such
      small metastases cannot be safely overlooked. The use of immunohistochemistry
      (IHC) to detect keratin proteins will reveal metastatic breast carcinoma in about
      18% of axillary lymph nodes that appear negative on routine stains. The
      preponderance of evidence to date suggests a significantly poorer prognosis in
      patients with such occult metastases, although data from large prospective
      studies are lacking. Molecular techniques such as polymerase chain reaction (PCR)
      offer even more sensitive methods for detecting occult metastasis in SLNs,
      although false positives are a particular problem in techniques that do not
      permit morphologic correlation, and for now they remain a research tool.
      Intraoperative examination of the SLN permits a completion axillary dissection to
      be performed during the same procedure if metastatic tumor is found; however,
      intraoperative techniques such as cytologic examination and frozen section lack
      sensitivity, and can result in loss of up to 50% of the SLN tissue. A proposal
      for optimal pathologic examination of the SLN is offered based on the above data.

PMID- 16958995
TI  - Histopathologic examination of the sentinel lymph nodes.
AB  - Sentinel lymph nodes (SLNs) are the most likely site of regional metastasis.
      Their step sectioning and cytokeratin immunohistochemistry (IHC) result in the
      upstaging of breast cancer. The heterogeneity of histologic methods is partially
      responsible for differences in nodal upstaging of the disease in different
      reports. Intraoperative assessment might be done by both frozen sections and
      imprint cytology; both methods have advantages and disadvantages. Several
      guidelines relating to the histopathology of sentinel nodes, including the recent
      European Working Group for Breast Screening Pathology guidelines, are briefly
      summarized. These latter advocate multilevel assessment of grossly or
      intraoperatively negative sentinel nodes with levels separated by a maximum of 1
      mm and allow IHC in their assessment, although this latter method is not
      mandatory. Both methods of intraoperative evaluation are allowable. There are
      also minimum requirements for the reports on sentinel node histology. For
      example, the reports should include the extent of nodal involvement, the method
      used for their identification, and preferably the method used for investigating
      the sentinel nodes, even if the results are negative. These guidelines are
      intended to form the basis for national guidelines in European countries.

PMID- 16958996
TI  - Sentinel lymph node biopsy alone has no adverse impact on the survival of
      patients with breast cancer.
AB  - We do not yet know the results from multicenter randomized trials comparing
      survival after sentinel lymph node biopsy (SLNB) alone and axillary lymph node
      dissection (ALND). Therefore, in this study, the prognostic significance of the
      type of axillary surgery is analyzed in combination with other known prognostic
      factors in patients with breast cancer. In a series of 1325 consecutive patients
      with unilateral breast cancer who underwent SLNB between January 1999 and June
      2004 at a single institution, 884 underwent SLNB alone following an
      intraoperative negative histologic investigation and 441 underwent ALND. Disease
      free survival (DFS) and overall survival (OS) were analyzed to correlate with
      clinicopathologic features and treatment methods using both univariate and
      multivariate analyses Cox proportional hazard regression models. With a median
      follow-up period of 31 months, 29 (3.3%) and 37 (8.4%) patients relapsed after
      SLNB alone and ALND, respectively. Tumor size (Tis, T1-2 versus T3-4), histologic
      nodal involvement (negative versus positive), nuclear grade (NG) (1, 2 versus 3),
      lymphatic vessel invasion (LVI) (absent, weak versus intense), estrogen receptor
      (ER) status (positive versus negative), type of axillary surgery (SLNB alone
      versus ALND), type of breast surgery (partial versus total mastectomy), and
      radiation therapy (yes versus no) significantly correlated with DFS by univariate
      analysis, demonstrating better DFS in the former category than the latter for
      each variable. The multivariate analysis revealed that NG, LVI, ER status, and
      radiation therapy significantly correlated with DFS, and ER and histologic nodal
      involvement correlated with OS. As the type of axillary surgery had no impact on
      the prognosis of patients with breast cancer, a SLNB alone is safe as determined
      by a negative histologic investigation.

PMID- 16958997
TI  - Breast conservation: evolution of surgical strategies.
AB  - The surgical strategy for breast cancer has changed considerably over the last
      decade. Breast-conserving therapy (BCT) is now standard treatment. Today, at
      least three out of four breast cancer patients are, in principle, eligible for
      BCT. However, several specific factors must be considered to choose the correct
      surgical strategy. This review provides a scientific overview of the history,
      surgical methodology, and specific aspects of BCT.

PMID- 16958998
TI  - Oncoplastic techniques in the conservative surgical treatment of breast cancer:
      an overview.
AB  - Conservative surgery has become a well-established alternative to mastectomy in
      the treatment of breast cancer. However, in case of larger lesions or small-size
      breasts, the removal of adequate volumes of breast tissue to achieve tumor-free
      margins and reduce the risk of local relapse may compromise the cosmetic outcome,
      causing unpleasant results. In order to address this issue, new surgical
      techniques, so-called oncoplastic techniques, have been introduced in recent
      years to optimize the efficacy of conservative surgery both in terms of local
      control and cosmetic results. This article discusses the indications, advantages,
      and limitations of these techniques and their results in terms of local
      recurrence and overall survival.

PMID- 16958999
TI  - CIH-Tokyo experience with breast-conserving surgery without radiotherapy: 6.5
      year follow-up results of 1462 patients.
AB  - When breast-conserving therapy was introduced at the Cancer Institute Hospital
      (CIH) in Tokyo in 1986, we instituted our own strategy as follows: 1) every
      effort is to be made for complete tumor resection while avoiding deformity of the
      breast, and 2) radiotherapy (RT) is applied only to the patients with positive
      surgical margins. This is, in turn, to clarify the group of patients in whom
      postoperative RT can be safely spared. Among 9670 patients operated on for
      primary breast cancer during the 16.5 year period from 1986 to 2002 at CIH, there
      were 2449 patients who underwent breast-conserving surgery (BCS). During the 6.5
      years mean follow-up period, ipsilateral intrabreast tumor recurrence (IBTR)
      developed in 99 of the 2449 patients, with an overall rate of 4.0% and an annual
      rate of 0.62%. These 2449 patients were categorized into four subgroups according
      to either negative or positive margins and with or without radiotherapy. The IBTR
      rates and the number of patients in each subgroup were 5.5% in 1351 margin(-)RT(
      ) patients, 1.0% in 307 margin(-)RT(+) patients, 2.4% in 680 margin(+)RT(+)
      patients, and 4.5% in 111 margin(+)RT(-) patients. These results either with or
      without RT seem to be quite comparable to or even better than the results of BCS
      with RT reported from Western countries, where less emphasis seems to be placed
      on completeness of the local tumor resection with BCS, while RT is administered
      to basically all patients following BCS. IBTR was categorized into true
      recurrence (TR) and second primary lesion (SP) according to the margin status at
      the time of BCS, the former being lesions developed in patients with positive
      margins and the latter being those in patients with negative margins. It was
      demonstrated that in patients with positive margins, TR was much more common than
      SP, whereas in patients with negative margins, these incidences were just the
      opposite (i.e., TR was 60% less common than SP) and postoperative RT was
      effective in preventing both TR and SP, the effect on the latter being much more
      striking. With RT, the incidence of developing TR in patients who had positive
      margins was reduced to almost equal to that in margin(-) patients treated with no
      RT. Our method of IBTR categorization is based on biological consideration and
      detailed histopathologic examination, and appears to be the only biologically
      reasonable means so far that has been proposed for distinction between these two
      biologically different entities. TR and SP can be further reduced to
      exceptionally low levels in patients who received RT despite negative margins,
      though it would not seem reasonable to administer RT to all of these patients
      because the actual number of patients who would benefit is comparatively small.
      From these observations, it seems that our imaging, pathologic examination, and
      surgical approaches for patients who are candidates for BCS have been highly
      valid, and our criteria for sparing postoperative RT as well as categorization of
      IBTR into TR and SP are quite appropriate. Although our results with BCS seem to
      deserve wide recognition, they are not from randomized clinical trials, so the
      findings must be confirmed by a study in order to investigate whether the results
      at CIH can be applied generally at other institutions.

PMID- 16959000
TI  - MammoSite balloon brachytherapy: errors, pitfalls, and technical issues for a
      practicing surgeon.
AB  - This article describes the technical aspects of insertion of the MammoSite
      radiation therapy system for patients with T1-2 disease. Practicing breast
      surgeons should be aware of the errors and pitfalls, the importance of cosmetic
      issues, and patient selection procedures.

PMID- 16959001
TI  - Galectin-9, a novel prognostic factor with antimetastatic potential in breast
      cancer.
AB  - Galectin-9, a member of the beta-galactoside-binding animal lectin family, is
      involved in various cellular biological events, including aggregation and
      apoptosis, adhesion of cancer cells, and dendritic cell maturation. We recently
      reported the relationship between galectin-9 expression in tumor tissue and
      distant metastasis in breast cancer. Tumors in 42 of the 84 patients were
      galectin-9-positive, and tumors in 19 of the 21 patients with distant metastasis
      were galectin-9-negative, assessed by immunohistochemistry. The cumulative
      distant metastasis-free survival ratio for galectin-9-positive patients was
      better than for the galectin-9-negative group (p < 0.0001). Multivariate analysis
      revealed that galectin-9 status influenced distant metastasis independent of and
      much more than lymph node metastasis. MCF-7 subclones with a high level of
      galectin-9 expression formed tight clusters during proliferation in vitro,
      whereas a subclone (K10) with the lowest level of galectin-9 expression did not.
      However, K10 cells stably transfected with a galectin-9 expression vector
      aggregated in nude mice as well as in culture. Ectopic expression of galectin-9
      also reduced MCF-7 cell adhesion to extracellular matrix proteins.

PMID- 16959002
TI  - Human leukocyte antigen as a predictive factor of developing bilateral breast
      cancer in Japanese women.
AB  - To investigate the relationship between human leukocyte antigen (HLA) type and
      bilateral breast cancer, a total of 213 female breast cancer patients were
      entered into this study. The lymphocyte cytotoxicity test was used for HLA
      typing. HLA frequency and haplotype antigen frequency were calculated with a
      microcomputer. A chi-squared test was used for comparing HLA frequency. At the
      start point of follow-up, 187 patients (87.8%) had unilateral and 26 patients
      (12.2%) had bilateral breast cancer. After a 10-year follow-up, 183 patients
      (85.9%) were unilateral and 30 patients (14.1%) were bilateral. Haplotype
      frequency of A24-Cw7 was significantly higher in bilateral breast cancer patients
      compared with unilateral breast cancer patients (p < 0.001). After the 10-year
      follow-up, 4 of 187 patients (2.1%) with unilateral breast cancer developed
      bilateral breast cancer. Two of 19 patients (10.5%) with haplotype A24-Cw7
      developed bilateral breast cancer, whereas only 2 of 168 patients (1.2%) without
      haplotype A24-Cw7 developed bilateral breast cancer (p < 0.01). The true
      frequency of developing contralateral breast cancer in patients with haplotype
      A24-Cw7 was 93 per 100,000 per year. The risk of bilateral breast cancer in
      patients with haplotype A24 and Cw7 is 12 times higher compared with those
      without the haplotype. HLA typing is useful for selecting patients who are at
      high risk of contralateral breast cancer.

PMID- 16959003
TI  - Clinical significance of multidetector-row computed tomography in breast surgery.
AB  - Several reports support the association of higher ipsilateral breast tumor
      recurrence rates with positive or intermediate margins compared with negative
      pathologic margins. Precise evaluation of tumor extension and adequate surgical
      margin are important factors affecting tumor recurrence after breast-conserving
      surgery (BCS). Many studies have reported the utility of magnetic resonance
      imaging (MRI) for diagnosing the tumor extension of breast cancer, but few have
      evaluated the utility of multidetector-row computed tomography (MDCT). The
      results of this study show the clinical significance of MDCT for detecting cancer
      extension and demonstrate the clinical role of MDCT in BCS. Subjects comprised
      136 patients grouped into two categories based on whether or not tumor extension
      was evaluated with MDCT preoperatively. The positive surgical margin rate and
      breast conservation rate were analyzed in each group and the clinical role of
      MDCT in BCS was evaluated. Moreover, evaluation of intraductal extension was done
      both with MDCT and histologically, and computed tomography (CT)-pathologic
      correlations were examined retrospectively. Finally, the margin-positive cases
      were analyzed in relation to their clinical characteristics. Sensitivity,
      specificity, positive predictive value, and negative predictive value for
      detection of the intraductal component were 71.8%, 85.7%, 82.1%, and 76.9%,
      respectively. The positive surgical margin rate and conservation rate are 7.46%
      and 81.9%, respectively, for those who were diagnosed with MDCT preoperatively;
      their corresponding rates without MDCT were 16.67% and 67.9%. Most margin
      positive patients have remarkable lymphatic space invasion. Positive surgical
      margins were often recognized toward the nipple. For diagnosing the intraductal
      extension, MDCT shows sufficient diagnosability. Moreover, MDCT can provide
      appropriate information for the determination of adequate surgical margins and
      contribute to increases in breast conservation rates.

PMID- 16959004
TI  - Endoscopic and histologic findings of intraductal lesions presenting with nipple
      discharge.
AB  - To improve the utility of mammary ductoscopy, we investigated the correlation
      between endoscopic findings and histologic findings using intraductal biopsy
      specimens. Seventy-one intraductal biopsy specimens obtained from 63 patients
      between October 2001 and March 2004 were analyzed retrospectively. All specimens
      were obtained from monotonous intraductal lesions immediately after observation
      by mammary ductoscopy and were composed of a pure histologic subtype. With regard
      to endoscopic findings, color was classified as yellow, red, white, or colorless,
      and morphology was classified as spherical, lobular, mulberry, or amorphous. The
      histologic subtype was classified as papillotubular, papillary, degenerated,
      papillary cancer, solid-type ductal carcinoma in situ (DCIS), or cribriform
      cancer. The relationship between histologic diagnosis, color, and morphology was
      investigated. Intraductal biopsy specimens included 25 specimens of carcinoma and
      46 specimens of papilloma. There was no significant correlation between color and
      diagnosis. Fourteen of 25 carcinoma specimens were amorphous, and amorphous
      morphology was significantly suggestive of malignancy (p < 0.001). Further,
      cribriform cancer was associated with amorphous morphology and yellow color.
      Morphology may be a useful endoscopically delineated parameter for
      differentiating intraductal lesions.

PMID- 16959005
TI  - Percutaneous excisional biopsy of palpable breast masses under ultrasound
      visualization.
AB  - A palpable breast mass is a common reason for surgical consultation. Our goal was
      to determine whether ultrasound-guided vacuum-assisted core biopsy (US-VACB) is
      safe and effective in completely removing presumed benign palpable breast masses.
      We conducted a cohort study of 201 consecutive patients with presumed benign
      palpable masses who underwent removal with US-VACB. The main outcome measured was
      the successful removal of palpable masses. Palpable masses were successfully
      removed with US-VACB in 99% of cases; 2% were cancer and 7.5% were atypical
      ductal hyperplasia or phyllodes tumor. Two clinical recurrences representing a
      seroma were seen on follow-up. US-VACB is safe and effective in the initial
      diagnosis and management of presumed benign palpable breast masses. It provides
      the benefits of percutaneous biopsy and the palpable abnormality no longer
      remains.

PMID- 16959006
TI  - Comments on the initial papers from Te Rau Hinengaro: the New Zealand Mental
      Health Survey.

PMID- 16959007
TI  - Implications for intervention and prevention from the New Zealand and Australian
      mental health surveys.

PMID- 16959008
TI  - National surveys of mental disorders: are they researching scientific facts or
      constructing useful myths?

PMID- 16959009
TI  - Te Rau Hinengaro: the New Zealand Mental Health Survey: overview of methods and
      findings.
AB  - OBJECTIVE: To estimate the prevalence and severity of anxiety, mood, substance
      and eating disorders in New Zealand, and associated disability and treatment.
      METHOD: A nationwide face-to-face household survey of residents aged 16 years and
      over was undertaken between 2003 and 2004. Lay interviewers administered a
      computerized fully structured diagnostic interview, the World Health Organization
      World Mental Health Survey Initiative version of the Composite International
      Diagnostic Interview. Oversampling doubled the number of Maori and quadrupled the
      number of Pacific people. The outcomes reported are demographics, period
      prevalences, 12 month severity and correlates of disorder, and contact with the
      health sector, within the past 12 months. RESULTS: The response rate was 73.3%.
      There were 12,992 participants (2,595 Maori and 2,236 Pacific people). Period
      prevalences were as follows: 39.5% had met criteria for a DSM-IV mental disorder
      at any time in their life before interview, 20.7% had experienced disorder within
      the past 12 months and 11.6% within the past month. In the past 12 months, 4.7%
      of the population experienced serious disorder, 9.4% moderate disorder and 6.6%
      mild disorder. A visit for mental health problems was made to the health-care
      sector in the past 12 months by 58.0% of those with serious disorder, 36.5% with
      moderate disorder, 18.5% with mild disorder and 5.7% of those not diagnosed with
      a disorder. The prevalence of disorder and of serious disorder was higher for
      younger people and people with less education or lower household income. In
      contrast, these correlates had little relationship to treatment contact, after
      adjustment for severity. Compared with the composite Others group, Maori and
      Pacific people had higher prevalences of disorder, unadjusted for
      sociodemographic correlates, and were less likely to make treatment contact, in
      relation to need. CONCLUSIONS: Mental disorder is common in New Zealand. Many
      people with current disorder are not receiving treatment, even among those with
      serious disorder.

PMID- 16959010
TI  - Prevalence, interference with life and severity of 12 month DSM-IV disorders in
      Te Rau Hinengaro: the New Zealand Mental Health Survey.
AB  - OBJECTIVE: To estimate the 12 month prevalence of DSM-IV disorders in New
      Zealand, and associated interference with life and severity. METHOD: A nationally
      representative face-to-face household survey carried out in 2003-2004. A fully
      structured diagnostic interview, the World Health Organization World Mental
      Health Survey Initiative version of the Composite International Diagnostic
      Interview (CIDI 3.0) was used. There were 12,992 completed interviews from
      participants aged 16 years and over. The overall response rate was 73.3%. In this
      paper the outcomes reported are 12 month prevalence, interference with life and
      severity for individual disorders. RESULTS: The prevalence of any disorder in the
      past 12 months was 20.7%. The prevalences for disorder groups were: anxiety
      disorders 14.8%, mood disorders 7.9%, substance use disorders 3.5%, eating
      disorders 0.5%. The highest prevalences for individual disorders were for
      specific phobia (7.3%), major depressive disorder (5.7%) and social phobia
      (5.1%). Interference with life was higher for mood disorders than for anxiety
      disorders. Drug dependence, bipolar disorder and dysthymia had the highest
      proportion of severe cases (over 50%), when severity was assessed over the
      disorder itself and all comorbid disorders. Overall, only 31.7% of cases were
      classified as mild with 45.6% moderate and 22.7% serious. CONCLUSIONS: Compared
      with other World Mental Health survey sites New Zealand has relatively high
      prevalences, although almost always a little lower than for the US. For all
      disorders, except specific phobia, interference with life was reported to be
      moderate, on average, which has lead to less than a third of cases being
      classified as mild. Most people who have ever met full DSM-IV criteria, including
      the impairment criterion, and who experience symptoms or an episode in the past
      12 months find that their disorders impact on their lives to a non-trivial
      extent.

PMID- 16959011
TI  - Twelve-month and lifetime health service use in Te Rau Hinengaro: The New Zealand
      Mental Health Survey.
AB  - OBJECTIVE: To estimate the 12 month and lifetime use of health services for
      mental health problems. METHOD: A nationwide face-to-face household survey
      carried out in 2003-2004. A fully structured diagnostic interview, the World
      Health Organization Composite International Diagnostic Interview (CIDI 3.0) was
      used. There were 12 992 completed interviews from participants aged 16 years and
      over. The overall response rate was 73.3%. In this paper, the outcomes reported
      are 12 month and lifetime health service use for mental health and substance use
      problems. RESULTS: Of the population, 13.4% had a visit for a mental health
      reason in the 12 months before interview. Of all 12 month cases of mental
      disorder, 38.9% had a mental health visit to a health or non-health-care provider
      in the past 12 months. Of these 12 month cases, 16.4% had contact with a mental
      health specialist, 28.3% with a general medical provider, 4.8% within the human
      services sector and 6.9% with a complementary or alternative medicine
      practitioner. Most people with lifetime disorders eventually made contact if
      their disorder continued. However, the percentages seeking help at the age of
      onset were small for most disorders and several disorders had large percentages
      who never sought help. The median duration of delay until contact varies from 1
      year for major depressive disorder to 38 years for specific phobias. CONCLUSIONS:
      A significant unmet need for treatment for people with mental disorder exists in
      the New Zealand community, as in other comparable countries.

PMID- 16959012
TI  - Lifetime prevalence and projected lifetime risk of DSM-IV disorders in Te Rau
      Hinengaro: the New Zealand Mental Health Survey.
AB  - OBJECTIVE: To estimate the lifetime prevalence and projected lifetime risk at age
      75 years of DSM-IV disorders in New Zealand. METHOD: A nationwide face-to-face
      household survey carried out in 2003-2004. A fully structured diagnostic
      interview, the World Health Organization Composite International Diagnostic
      Interview (CIDI 3.0), was used. There were 12,992 completed interviews from
      participants aged 16 years and over. The overall response rate was 73.3%. In this
      paper, the outcomes reported are lifetime prevalence and projected lifetime risk
      at age 75 years. RESULTS: The lifetime prevalence of any disorder was 39.5%. The
      lifetime prevalences for disorder groups were: anxiety disorders, 24.9%; mood
      disorders, 20.2%; substance use disorders, 12.3%; and eating disorders, 1.7%. The
      prevalences for all disorders were higher in the younger age groups. Females had
      higher prevalences of anxiety, mood and eating disorders compared with males;
      males had higher prevalences of substance use disorders. The estimated projected
      lifetime risk of any disorder at age 75 years was 46.6% with the median age of
      onset being 18 years. Adjustment for age, sex, education and household income did
      not remove all differences between Maori and the composite other ethnic group in
      the risk of disorder (hazard ratio = 1.1-1.4). After adjustment, hazard ratios
      for Pacific people ranged from 0.8 to 2.5. CONCLUSIONS: These results confirm
      those of other studies: mental disorders are relatively common and tend to have
      early onset. Females are more likely to experience anxiety, mood and eating
      disorders than males, who experience more substance use disorders. Adjustment for
      socioeconomic factors and demography does not explain all ethnic differences,
      although remaining differences are small relative to cohort and even sex
      differences.

PMID- 16959013
TI  - Mental disorder comorbidity in Te Rau Hinengaro: the New Zealand Mental Health
      Survey.
AB  - OBJECTIVE: To show the extent and patterning of 12 month mental disorder
      comorbidity in the New Zealand population, and its association with case
      severity, suicidality and health service utilization. METHOD: A nationwide face
      to-face household survey was carried out in October 2003 to December 2004 with
      12,992 participants aged 16 years and over, achieving a response rate of 73.3%.
      The measurement of mental disorder was with the World Mental Health Survey
      Initiative version of the Composite International Diagnostic Interview (CIDI
      3.0). Comorbidity was analysed with hierarchy, consistent with a clinical
      approach to disorder count. RESULTS: Comorbidity occurred among 37% of 12 month
      cases. Anxiety and mood disorders were most frequently comorbid. Strong bivariate
      associations occurred between alcohol and drug use disorders and, to a lesser
      extent, between substance use disorders and some anxiety and mood disorders.
      Comorbidity was associated with case severity, with suicidal behaviour
      (especially suicide attempts) and with health sector use (especially mental
      health service use). CONCLUSION: The widespread nature of mental disorder
      comorbidity has implications for the configuration of mental health services and
      for clinical practice.

PMID- 16959014
TI  - Mental-physical comorbidity in Te Rau Hinengaro: the New Zealand Mental Health
      Survey.
AB  - OBJECTIVE: To estimate the prevalence of chronic physical conditions, and the
      risk factors for those conditions, among those with 12 month mental disorder; to
      estimate the prevalence of 12 month mental disorder among those with chronic
      physical conditions. METHOD: A nationally representative face-to-face household
      survey was carried out in October 2003 to December 2004 with 12,992 participants
      aged 16 years and over, achieving a response rate of 73.3%. Mental disorders were
      measured with the World Mental Health version of the Composite International
      Diagnostic Interview (CIDI 3.0). Physical conditions were self-reported. All
      associations are reported adjusted for age and sex. RESULTS: People with (any)
      mental disorder, relative to those without mental disorder, had higher
      prevalences of several chronic physical conditions (chronic pain, cardiovascular
      disease, high blood pressure and respiratory conditions) and chronic condition
      risk factors (smoking, overweight/obesity, hazardous alcohol use). Around a
      quarter of people with chronic physical conditions had a comorbid mental disorder
      compared with 15% of the population without chronic conditions. Significant
      relationships occurred between some mental disorders and obesity, cardiovascular
      disease and diabetes for females, but not for males. CONCLUSIONS: This paper
      provides evidence of substantial comorbidity between mental disorders and chronic
      physical conditions in New Zealand. This should be borne in mind by clinicians
      working in both mental health and medical services.

PMID- 16959015
TI  - Disability in Te Rau Hinengaro: the New Zealand Mental Health Survey.
AB  - OBJECTIVE: To show the disability associated with 1 month mental disorders and
      chronic physical conditions for the New Zealand population, controlling for
      comorbidity, age and sex. METHOD: A nationally representative face-to-face
      household survey was carried out from October 2003 to December 2004 with 12,992
      participants aged 16 years and over, achieving a response rate of 73.3%. Mental
      disorders were measured with the World Mental Health (WMH) Survey Initiative
      version of the Composite International Diagnostic Interview (CIDI 3.0).
      Disability was measured with the WMH Survey Initiative version of the World
      Health Organization Disability Assessment Schedule (WMH WHO-DAS) in the long-form
      subsample (n = 7435). Outcomes include five WMH WHO-DAS domain scores for those
      with 1 month mental disorders and with chronic physical conditions. RESULTS: Mood
      disorders were associated with more disability than anxiety or substance use
      disorders. Experiencing multiple mental disorders was associated with substantial
      role impairment. Mental disorders and chronic physical conditions were associated
      with similar degrees of disability on average. The combination of mental and
      physical disorders had additive effects on associated disability. CONCLUSIONS:
      Mood disorders are disabling. The investigation of disability in relation to 1
      month rather than 12 month disorders is likely to provide a clearer indication of
      the disability associated with mood disorders. Although some researchers have
      queried whether negative mood can lead to 'over-reporting' of disability, recent
      conceptualizations of disability provide a perspective which may ease such
      concerns. Comorbidity, of mental disorders or of mental and physical disorders,
      is disabling.

PMID- 16959016
TI  - Suicidal behaviour in Te Rau Hinengaro: the New Zealand Mental Health Survey.
AB  - OBJECTIVE: To describe prevalence and correlates of suicidal behaviour in the New
      Zealand population aged 16 years and over. METHOD: Data are from Te Rau
      Hinengaro: The New Zealand Mental Health Survey, a nationally representative
      household survey conducted from October 2003 to December 2004 in a sample of
      12,992 participants aged 16 years and over to study prevalences and correlates of
      mental disorders assessed using the World Mental Health Composite International
      Diagnostic Interview. Lifetime and 12 month prevalences and onset distributions
      for suicidal ideation, plans and attempts, and sociodemographic and mental
      disorder correlates of these behaviours were examined. RESULTS: Lifetime
      prevalences were 15.7% for suicidal ideation, 5.5% for suicide plan and 4.5% for
      suicide attempt, and were consistently significantly higher in females than in
      males. Twelve-month prevalences were 3.2% for ideation, 1.0% for plan and 0.4%
      for attempt. Risk of ideation in the past 12 months was higher in females,
      younger people, people with lower educational qualifications, and people with low
      household income. Risk of making a plan or attempt was higher in younger people
      and in people with low household income. After adjustment for sociodemographic
      factors, there were no ethnic differences in ideation, although Maori and Pacific
      people had elevated risks of plans and attempts compared with non-Maori non
      Pacific people. Individuals with a mental disorder had elevated risks of ideation
      (11.8%), plan (4.1%) and attempt (1.6%) compared with those without mental
      disorder. Risks of suicidal ideation, plan and attempt were associated with mood
      disorder, substance use disorder and anxiety disorder. Major depression was the
      specific disorder most strongly associated with suicidal ideation, plan and
      attempt. Less than half of those who reported suicidal behaviours within the past
      12 months had made visits to health professionals within that period. Less than
      one-third of those who had made attempts had received treatment from a
      psychiatrist. CONCLUSIONS: Risks of making a suicide plan or attempt were
      associated with mental disorder and sociodemographic disadvantage. Most people
      with suicidal behaviours had not seen a health professional for mental health
      problems during the time that they were suicidal.

PMID- 16959017
TI  - Ethnic comparisons of the 12 month prevalence of mental disorders and treatment
      contact in Te Rau Hinengaro: the New Zealand Mental Health Survey.
AB  - OBJECTIVE: To compare ethnic groups for the 12 month prevalence of mental
      disorders and 12 month treatment contact in Te Rau Hinengaro: The New Zealand
      Mental Health Survey. METHOD: Te Rau Hinengaro: The New Zealand Mental Health
      Survey, undertaken in 2003 and 2004, was a nationally representative face-to-face
      household survey of 12,992 New Zealand adults aged 16 years and over, including
      Maori (n = 2595), Pacific people (n = 2236) and a composite Other ethnic group
      (predominantly European) (n = 8161). Ethnicity was measured using the 2001 census
      ethnicity question. A fully structured diagnostic interview, the World Health
      Organization World Mental Health Survey Initiative version of the Composite
      International Diagnostic Interview (CIDI 3.0) was used to measure disorder. The
      overall response rate was 73.3%. RESULTS: The 12 month prevalence of any mental
      disorder was highest in Maori (29.5%; 26.6, 32.4), followed by Pacific people
      (24.4%; 21.2, 27.6) and Others (19.3%; 18.0, 20.6). Adjustment for age, sex,
      education and household income reduced differences: Maori (23.9%; 21.3, 26.4),
      Pacific (19.2%; 16.4, 22.1) and Other (20.3%; 18.9, 21.6). A similar pattern was
      seen for serious disorder and most individual disorders or disorder groups. After
      adjustment, Maori were most different from Pacific people and Others for
      substance use disorder. Both Maori and Pacific people had a higher prevalence of
      bipolar disorder than Others. Pacific people had the lowest prevalence of major
      depressive disorder. Among those with disorder, the proportion with a visit for
      mental health problems to any service was highest among Others (41.1%; 38.1,
      44.1), with Maori (32.5%; 28.3, 36.7) intermediate and Pacific (25.4%, 19.4,
      31.4) lowest. Adjustment did not alter ethnic differences in service contact.
      CONCLUSION: Maori, and to a lesser extent Pacific people, have a higher
      prevalence of 12 month mental disorders than Others. Differences are reduced
      after adjusting for sociodemographic correlates. Relative to need, Pacific people
      in particular and Maori are less likely than Others to have contact with services
      (health or non-health), regardless of sociodemographic circumstances.

PMID- 16959018
TI  - Prevalence of mental disorders among Maori in Te Rau Hinengaro: the New Zealand
      Mental Health Survey.
AB  - OBJECTIVE: To describe the prevalence of mental disorders (period prevalence
      across aggregated disorders, 12 month and lifetime prevalence) among Maori in Te
      Rau Hinengaro: The New Zealand Mental Health Survey. METHOD: Te Rau Hinengaro:
      The New Zealand Mental Health Survey, undertaken between 2003 and 2004, was a
      nationally representative face-to-face household survey of 12,992 New Zealand
      adults aged 16 years and over, including 2,595 Maori. Ethnicity was measured
      using the 2001 New Zealand census ethnicity question. A fully structured
      diagnostic interview, the World Health Organization World Mental Health Survey
      Initiative version of the Composite International Diagnostic Interview (CIDI
      3.0), was used to measure disorder. The overall response rate was 73.3%. This
      paper presents selected findings for the level and pattern of mental disorder
      prevalence among Maori. RESULTS: Maori lifetime prevalence of any disorder was
      50.7%, 12 month prevalence 29.5% and 1 month prevalence 18.3%. The most common 12
      month disorders were anxiety (19.4%), mood (11.4%) and substance (8.6%) disorders
      and the most common lifetime disorders were anxiety (31.3%), substance (26.5%)
      and mood (24.3%) disorders. Levels of lifetime comorbidity were high with 12
      month prevalence showing 16.4% of Maori with one disorder, 7.6% with two
      disorders and 5.5% with three or more disorders. Twelve-month disorders were more
      common in Maori females than in males (33.6%vs 24.8%) and in younger age groups:
      16-24 years, 33.2%; 25-44 years, 32.9%; 45-64 years, 23.7%; and 65 years and
      over, 7.9%. Disorder prevalence was greatest among Maori with the lowest
      equivalized household income and least education. However, differences by
      urbanicity and region were not significant. Of Maori with any 12 month disorder,
      29.6% had serious, 42.6% had moderate and 27.8% had mild disorders. CONCLUSION:
      Mental disorders overall and specific disorder groups (anxiety, mood and
      substance) are common among Maori and measures of severity indicate that
      disorders have considerable health impact. Findings provide a platform for
      informing public health policy and health sector responses to meeting mental
      health needs of Maori.

PMID- 16959019
TI  - Twelve-month and lifetime prevalences of mental disorders and treatment contact
      among Pacific people in Te Rau Hinengaro: the New Zealand Mental Health Survey.
AB  - OBJECTIVE: To show the 12 month and lifetime prevalences of mental disorders and
      12 month treatment contact of Pacific people in Te Rau Hinengaro: The New Zealand
      Mental Health Survey. METHOD: Te Rau Hinengaro: The New Zealand Mental Health
      Survey, undertaken in 2003 and 2004, was a nationally representative face-to-face
      household survey of 12,992 New Zealand adults aged 16 years and over including
      Maori (n = 2457), Pacific people (n = 2236), people of mixed Pacific and Maori
      ethnicity (n = 138), and 'Others' (a composite group of predominantly European
      descent) (n = 8161). Ethnicity was measured by self-identified ethnicity using
      the New Zealand 2001 Census of Population and Dwellings question. A fully
      structured diagnostic interview, the World Health Organization World Mental
      Health Survey Initiative version of the Composite International Diagnostic
      Interview (CIDI 3.0), was used to measure disorders. The overall response rate
      was 73.3%. RESULTS: Pacific people have high rates of mental illness: the
      unadjusted 12 month prevalence for Pacific people was 25.0% compared with 20.7%
      for the total New Zealand population. There were also higher 12 month prevalences
      of suicidal ideation (4.5%) and suicide attempts (1.2%). Only 25.0% of Pacific
      people who had experienced a serious mental disorder had visited any health
      service for their mental health reason compared with 58.0% of the total New
      Zealand population. The prevalence of mental disorder was lower among Pacific
      people born in the Islands than among New Zealand-born Pacific people.
      CONCLUSION: Pacific people experience high prevalence of mental disorder and New
      Zealand-born Pacific people experience significantly higher prevalence than
      Island-born Pacific people.

PMID- 16959020
TI  - No association between the deficit syndrome in psychosis and summer birth in a
      Southern hemisphere country.

PMID- 16959021
TI  - Acute urinary retention associated with atomoxetine use.

PMID- 16959022
TI  - Response to Sheehan, Thurber and Sewall.

PMID- 16959023
TI  - Self-cannibalism: an unusual case of self-mutilation.

PMID- 16959024
TI  - Inhibition of tissue factor expression by hydroxyurea in polymorphonuclear
      leukocytes from patients with myeloproliferative disorders: a new effect for an
      old drug?
AB  - BACKGROUND: Polymorphonuclear leukocytes (PMN) from healthy subjects can produce
      and store tissue factor (TF), which is expressed on PMN surface upon in vitro
      stimulation with P-selectin. RESULTS: We report here that platelets and PMN from
      12 patients with myeloproliferative disorders (MPD) (six with polycythemia vera,
      six with essential thrombocythemia) show up regulation of P-selectin and TF,
      respectively, in the absence of any in vitro challenge. The number of circulating
      mixed platelet-PMN aggregates was also increased. PMN TF expression as well as
      mixed platelet-PMN aggregates, but not platelet P-selectin, were significantly
      reduced in six MPD patients after treatment with hydroxyurea (HU). In vitro
      studies performed on PMN separated from healthy donors confirmed HU effects (0
      1400 microm). HU prevented both P-selectin-induced TF expression and mixed cell
      aggregate formation. The inhibitory effect of HU was specific for P-selectin
      induced PMN activation, as it did not affect formyl-methionyl-leucyl
      phenylalanine-induced PMN TF expression. CONCLUSIONS: In MPD patients, platelet P
      selectin-mediated TF expression on circulating PMN may play a role in thrombus
      formation and represents a novel target for the antithrombotic activity of HU.

PMID- 16959025
TI  - Pregnancy loss, tissue factor pathway inhibitor deficiency and resistance to
      activated protein C.

PMID- 16959026
TI  - The use of non-wood forest products by migrants in a new settlement: experiences
      of a Visayan community in Palawan, Philippines.
AB  - Migrants are often constrained by a lack of knowledge regarding their new
      environment and require new skills for their livelihood. In Palawan, some of
      these necessary skills and knowledge are related to the collection and use of non
      wood forest products (NWFPs), many of which the migrants were previously not
      familiar with. The predominantly Visayan migrants have been successful in
      familiarizing themselves with the NWFPs in the surrounding forests, with
      assistance from some of the local indigenous people, in this case the Tagbanua,
      and from previous migrant settlers. The NWFPs they know about and the extent of
      use are presented. Currently, except for almaciga (Agathis philippinensis Warb.)
      resin and house-building materials, NWFPs are considered as supplements to
      agricultural products, not as main source of either subsistence or income.

PMID- 16959027
TI  - Novel IL10 gene family associations with systemic juvenile idiopathic arthritis.
AB  - Juvenile idiopathic arthritis (JIA) is the most common cause of chronic childhood
      disability and encompasses a number of disease subgroups. In this study we have
      focused on systemic JIA (sJIA), which accounts for approximately 11% of UK JIA
      cases. This study reports the investigation of three members of the IL10 gene
      family as candidate susceptibility loci in children with sJIA. DNA from 473
      unaffected controls and 172 patients with sJIA was genotyped for a single
      nucleotide polymorphism (SNP) in IL19 and IL20 and two SNPs in IL10. We examined
      evidence for association of the four SNPs by single marker and haplotype
      analysis. Significant differences in allele frequency were observed between cases
      and controls, for both IL10-1082 (p = 0.031) and IL20-468 (p = 0.028).
      Furthermore, examination of the haplotypes of IL10-1082 and IL20-468 revealed
      greater evidence for association (global p = 0.0006). This study demonstrates a
      significant increased prevalence of the low expressing IL10-1082 genotype in
      patients with sJIA. In addition, we show a separate association with an IL20
      polymorphism, and the IL10-1082A/IL20-468T haplotype. The two marker 'A-T'
      haplotype confers an odds ratio of 2.24 for sJIA. This positive association
      suggests an important role for these cytokines in sJIA pathogenesis.

PMID- 16959029
TI  - Fibrillar beta-amyloid peptide Abeta1-40 activates microglial proliferation via
      stimulating TNF-alpha release and H2O2 derived from NADPH oxidase: a cell culture
      study.
AB  - BACKGROUND: Alzheimer's disease is characterized by the accumulation of neuritic
      plaques, containing activated microglia and beta-amyloid peptides (Abeta).
      Fibrillar Abeta can activate microglia, resulting in production of toxic and
      inflammatory mediators like hydrogen peroxide, nitric oxide, and cytokines. We
      have recently found that microglial proliferation is regulated by hydrogen
      peroxide derived from NADPH oxidase. Thus, in this study, we investigated whether
      Abeta can stimulate microglial proliferation and cytokine production via
      activation of NADPH oxidase to produce hydrogen peroxide. METHODS: Primary mixed
      glial cultures were prepared from the cerebral cortices of 7-day-old Wistar rats.
      At confluency, microglial cells were isolated by tapping, replated, and treated
      either with or without Abeta. Hydrogen peroxide production by cells was measured
      with Amplex Red and peroxidase. Microglial proliferation was assessed under a
      microscope 0, 24 and 48 hours after plating. TNF-alpha and IL-1beta levels in the
      culture medium were assessed by ELISA. RESULTS: We found that 1 muM fibrillar
      (but not soluble) Abeta1-40 peptide induced microglial proliferation and caused
      release of hydrogen peroxide, TNF-alpha and IL-1beta from microglial cells.
      Proliferation was prevented by the NADPH oxidase inhibitor apocynin (10 microM),
      by the hydrogen peroxide-degrading enzyme catalase (60 U/ml), and by its mimetics
      EUK-8 and EUK-134 (20 microM); as well as by an antibody against TNF-alpha and by
      a soluble TNF receptor inhibitor. Production of TNF-alpha and IL-1beta, measured
      after 24 hours of Abeta treatment, was also prevented by apocynin, catalase and
      EUKs, but the early release (measured after 1 hour of Abeta treatment) of TNF
      alpha was insensitive to apocynin or catalase. CONCLUSION: These results indicate
      that Abeta1-40-induced microglial proliferation is mediated both by microglial
      release of TNF-alpha and production of hydrogen peroxide from NADPH oxidase. This
      suggests that TNF-alpha and NADPH oxidase, and its products, are potential
      targets to prevent Abeta-induced inflammatory neurodegeneration.

PMID- 16959028
TI  - Magnetic resonance mammography in the evaluation of recurrence at the prior
      lumpectomy site after conservative surgery and radiotherapy.
AB  - INTRODUCTION: The aim was to assess the value of magnetic resonance mammography
      (MRM) in the detection of recurrent breast cancer on the prior lumpectomy site in
      patients with previous conservative surgery and radiotherapy. METHODS: Between
      April 1999 and July 2003, 93 consecutive patients with breast cancer treated with
      conservative surgery and radiotherapy underwent MRM, when a malignant lesion on
      the site of lumpectomy was suspected by ultrasound and/or mammography. MRM scans
      were evaluated by morphological and dynamic characteristics. MRM diagnosis was
      compared with histology or with a 36-month imaging follow-up. Enhancing areas
      independent of the prior lumpectomy site, incidentally detected during the MRM,
      were also evaluated. RESULTS: MRM findings were compared with histology in 29
      patients and with a 36-month follow-up in 64 patients. MRM showed 90%
      sensitivity, 91.6% specificity, 56.3% positive predictive value and 98.7%
      negative predictive value for detection of recurrence on the surgical scar. MRM
      detected 13 lesions remote from the scar. The overall sensitivity, specificity,
      positive predictive value and negative predictive value of MRM for detection of
      breast malignancy were 93.8%, 90%, 62.5% and 98.8%, respectively. CONCLUSION: MRM
      is a sensitive method to differentiate recurrence from post-treatment changes at
      the prior lumpectomy site after conservative surgery and radiation therapy. The
      high negative predictive value of this technique can avoid unnecessary biopsies
      or surgical treatments.

PMID- 16959030
TI  - Charcot-Leyden crystals in a prostatic adenocarcinoma.
AB  - A transrectal needle biopsy from a 63-year-old man was decided because of a high
      prostatic specific antigen in the blood, and a hard right lobe in rectal
      examination. 10 examples were taken from each lobe. In 1 of 4 of the examples
      from the left lobe, which contained a small focus of adenocarcinoma, numerous
      eosinophils were observed to surround the carcinomatous focus and attack the
      carcinoma cells. Uniquely, at the same focus Charcot-Leyden crystals could be
      seen in the intraluminal space and stromal area. A carcinoma oriented eosinophil
      accumulation, and Charcot-Leyden crystals in prostate was not described before.

PMID- 16959031
TI  - Food, flavouring and feed plant traditions in the Tyrrhenian sector of
      Basilicata, Italy.
AB  - BACKGROUND: Research was carried out in the years 2002-2003 into food, flavouring
      and feed folk traditions of plants in the Tyrrhenian part of the Basilicata
      region (southern Italy). This area was colonized in ancient times by Greeks. Data
      was collected through field interviews, especially of farmers. METHODS: Field
      data were collected through structured interviews. The informants, numbered 49,
      belonged to families which had strong links with the traditional activities of
      the area. RESULTS: 61 taxa are cited, belonging to 26 botanical families, amongst
      which 44 used as food or flavouring and 22 for animal alimentation. Besides 7
      taxa are involved in rituals especially connected with agriculture and plant
      growth. CONCLUSION: The preservation of some rituals especially concerning
      agricultural plants is noteworthy in the area, together with a certain degree of
      continuity in food uses. Knowledge and rediscovery of recipes in human and animal
      diet could represent an economic potential for the area.

PMID- 16959032
TI  - First report of an HIV-1 triple recombinant of subtypes B, C and F in Buenos
      Aires, Argentina.
AB  - We describe the genetic diversity of currently transmitted strains of HIV-1 in
      men who have sex with men (MSM) in Buenos Aires, Argentina between 2000 and 2004.
      Nearly full-length sequence analysis of 10 samples showed that 6 were subtype B,
      3 were BF recombinant and 1 was a triple recombinant of subtypes B, C and F. The
      3 BF recombinants were 3 different unique recombinant forms. Full genome analysis
      of one strain that was subtype F when sequenced in pol was found to be a triple
      recombinant. Gag and pol were predominantly subtype F, while gp120 was subtype B;
      there were regions of subtype C interspersed throughout. The young man infected
      with this strain reported multiple sexual partners and sero-converted between May
      and November of 2004. This study reported for the first time the full genome
      analysis of a triple recombinant between subtypes B, C and F, that combines in
      one virus the three most common subtypes in South America.

PMID- 16959033
TI  - A randomized, double blind, cross-over, placebo-controlled clinical trial to
      assess the effects of Candesartan on the insulin sensitivity on non diabetic, non
      hypertense subjects with dysglyce mia and abdominal obesity. "ARAMIA".
AB  - BACKGROUND: The raising prevalence of type-2 diabetes mellitus and obesity has
      been recognized as a major problem for public health, affecting both developed
      and developing countries. Impaired fasting plasma glucose has been previously
      associated with endothelial dysfunction, higher levels of inflammatory markers
      and increased risk of developing insulin resistance and cardiovascular events.
      Besides life-style changes, the blockade of the renin-angiotensin system has been
      proposed as a useful alternative intervention to improve insulin resistance and
      decrease the number of new type-2 diabetes cases. The aim of this clinical trial
      is to study the effect of the treatment with Candesartan, an angiotensin II
      receptor antagonist, on the insulin resistance, the plasma levels of adipoquines,
      oxidative stress and prothrombotic markers, in a group of non diabetic, non
      hypertensive, dysglycemic and obese subjects. METHODS AND DESIGN: A randomized,
      double blind, cross-over, placebo-controlled, clinical trial was designed to
      assess the effects of Candesartan (up to 32 mg/day during 6 months) on the
      Homeostasis Model Assessment (HOMA) index, lipid profile, protrombotic state,
      oxidative stress and plasma levels of inflammatory markers. The participants will
      be recruited in the "Fundacion Cardiovascular de Colombia". Subjects who fullfil
      selection criteria will receive permanent educational, nutritional and exercise
      support during their participation in the study. After a 15 days-run-in period
      with placebo and life-style recommendations, the patients who have a treatment
      compliance equal or greater than 80% will be randomlly assigned to one of the
      treatment groups. Group A will receive Candesartan during 6 months and placebo
      during 6 months. Group B will receive placebo during the first 6 months, and
      then, Candesartan during the last 6 months. Control visits will be programed
      monthly and all parameters of interest will be evaluated every 6 months.
      HYPOTHESIS: Treatment with Candesartan, could improve the HOMA index, the
      response to the oral glucose tolerance test and reduce the plasma levels of
      adipoquines, oxidative stress and prothrombotic markers, in non diabetic, non
      hypertense subjects with dysglycemia and abdominal obesity, recruited from a
      population at high risk of developing insulin resistance. These effects are
      independent of the changes in arterial blood pressure. TRIAL REGISTRATION:
      NCT00319202.

PMID- 16959034
TI  - CHARGE syndrome.
AB  - CHARGE syndrome was initially defined as a non-random association of anomalies
      (Coloboma, Heart defect, Atresia choanae, Retarded growth and development,
      Genital hypoplasia, Ear anomalies/deafness). In 1998, an expert group defined the
      major (the classical 4C's: Choanal atresia, Coloboma, Characteristic ears and
      Cranial nerve anomalies) and minor criteria of CHARGE syndrome. Individuals with
      all four major characteristics or three major and three minor characteristics are
      highly likely to have CHARGE syndrome. However, there have been individuals
      genetically identified with CHARGE syndrome without the classical choanal atresia
      and coloboma. The reported incidence of CHARGE syndrome ranges from 0.1
      1.2/10,000 and depends on professional recognition. Coloboma mainly affects the
      retina. Major and minor congenital heart defects (the commonest cyanotic heart
      defect is tetralogy of Fallot) occur in 75-80% of patients. Choanal atresia may
      be membranous or bony; bilateral or unilateral. Mental retardation is variable
      with intelligence quotients (IQ) ranging from normal to profound retardation.
      Under-development of the external genitalia is a common finding in males but it
      is less apparent in females. Ear abnormalities include a classical finding of
      unusually shaped ears and hearing loss (conductive and/or nerve deafness that
      ranges from mild to severe deafness). Multiple cranial nerve dysfunctions are
      common. A behavioral phenotype for CHARGE syndrome is emerging. Mutations in the
      CHD7 gene (member of the chromodomain helicase DNA protein family) are detected
      in over 75% of patients with CHARGE syndrome. Children with CHARGE syndrome
      require intensive medical management as well as numerous surgical interventions.
      They also need multidisciplinary follow up. Some of the hidden issues of CHARGE
      syndrome are often forgotten, one being the feeding adaptation of these children,
      which needs an early aggressive approach from a feeding team. As the child
      develops, challenging behaviors become more common and require adaptation of
      educational and therapeutic services, including behavioral and pharmacological
      interventions.

PMID- 16959035
TI  - Identification of genes regulated by Wnt/beta-catenin pathway and involved in
      apoptosis via microarray analysis.
AB  - BACKGROUND: Wnt/beta-catenin pathway has critical roles in development and
      oncogenesis. Although significant progress has been made in understanding the
      downstream signaling cascade of this pathway, little is known regarding Wnt/beta
      catenin pathway modification of the cellular apoptosis. METHODS: To identify
      potential genes regulated by Wnt/beta-catenin pathway and involved in apoptosis,
      we used a stably integrated, inducible RNA interference (RNAi) vector to specific
      inhibit the expression and the transcriptional activity of beta-catenin in HeLa
      cells. Meanwhile, we designed an oligonucleotide microarray covering 1384
      apoptosis-related genes. Using oligonucleotide microarrays, a series of
      differential expression of genes was identified and further confirmed by RT-PCR.
      RESULTS: Stably integrated inducible RNAi vector could effectively suppress beta
      catenin expression and the transcriptional activity of beta-catenin/TCF.
      Meanwhile, depletion of beta-catenin in this manner made the cells more sensitive
      to apoptosis. 130 genes involved in some important cell-apoptotic pathways, such
      as PTEN-PI3K-AKT pathway, NF-kappaB pathway and p53 pathway, showed significant
      alteration in their expression level after the knockdown of beta-catenin.
      CONCLUSION: Coupling RNAi knockdown with microarray and RT-PCR analyses proves to
      be a versatile strategy for identifying genes regulated by Wnt/beta-catenin
      pathway and for a better understanding the role of this pathway in apoptosis.
      Some of the identified beta-catenin/TCF directed or indirected target genes may
      represent excellent targets to limit tumor growth.

PMID- 16959036
TI  - Generalization of DNA microarray dispersion properties: microarray equivalent of
      t-distribution.
AB  - BACKGROUND: DNA microarrays are a powerful technology that can provide a wealth
      of gene expression data for disease studies, drug development, and a wide scope
      of other investigations. Because of the large volume and inherent variability of
      DNA microarray data, many new statistical methods have been developed for
      evaluating the significance of the observed differences in gene expression.
      However, until now little attention has been given to the characterization of
      dispersion of DNA microarray data. RESULTS: Here we examine the expression data
      obtained from 682 Affymetrix GeneChips with 22 different types and we demonstrate
      that the Gaussian (normal) frequency distribution is characteristic for the
      variability of gene expression values. However, typically 5 to 15% of the samples
      deviate from normality. Furthermore, it is shown that the frequency distributions
      of the difference of expression in subsets of ordered, consecutive pairs of genes
      (consecutive samples) in pair-wise comparisons of replicate experiments are also
      normal. We describe a consecutive sampling method, which is employed to calculate
      the characteristic function approximating standard deviation and show that the
      standard deviation derived from the consecutive samples is equivalent to the
      standard deviation obtained from individual genes. Finally, we determine the
      boundaries of probability intervals and demonstrate that the coefficients
      defining the intervals are independent of sample characteristics, variability of
      data, laboratory conditions and type of chips. These coefficients are very
      closely correlated with Student's t-distribution. CONCLUSION: In this study we
      ascertained that the non-systematic variations possess Gaussian distribution,
      determined the probability intervals and demonstrated that the K(alpha)
      coefficients defining these intervals are invariant; these coefficients offer a
      convenient universal measure of dispersion of data. The fact that the K(alpha)
      distributions are so close to t-distribution and independent of conditions and
      type of arrays suggests that the quantitative data provided by Affymetrix
      technology give "true" representation of physical processes, involved in
      measurement of RNA abundance. REVIEWERS: This article was reviewed by Yoav Gilad
      (nominated by Doron Lancet), Sach Mukherjee (nominated by Sandrine Dudoit) and
      Amir Niknejad and Shmuel Friedland (nominated by Neil Smalheiser).

PMID- 16959037
TI  - Genetic analysis of the GRIK2 modifier effect in Huntington's disease.
AB  - BACKGROUND: In Huntington's disease (HD), age at neurological onset is inversely
      correlated with the length of the CAG trinucleotide repeat mutation, but can be
      modified by genetic factors beyond the HD gene. Association of a relatively
      infrequent 16 TAA allele of a trinucleotide repeat polymorphism in the GRIK2
      3'UTR with earlier than expected age at neurological onset has been suggested to
      reflect linkage disequilibrium with a functional polymorphism in GRIK2 or an
      adjacent gene. RESULTS: We have tested this hypothesis by sequencing all GRIK2
      exons, the exon-flanking sequences and 3'UTR in several individuals who were
      crucial to demonstrating the modifier effect, as they showed much earlier age at
      neurological onset than would be expected from the length of their HD CAG
      mutation. Though ten known SNPs were detected, no sequence variants were found in
      coding or adjacent sequence that could explain the modifier effect by linkage
      disequilibrium with the 16 TAA allele. Haplotype analysis using microsatellites,
      known SNPs and new variants discovered in the 3'UTR argues against a common
      ancestral origin for the 16 TAA repeat alleles in these individuals. CONCLUSION:
      These data suggest that the modifier effect is actually due to the TAA repeat
      itself, possibly via a functional consequence on the GRIK2 mRNA.

PMID- 16959038
TI  - Cytomegalovirus-induced embryopathology: mouse submandibular salivary gland
      epithelial-mesenchymal ontogeny as a model.
AB  - BACKGROUND: Human studies suggest, and mouse models clearly demonstrate, that
      cytomegalovirus (CMV) is dysmorphic to early organ and tissue development. CMV
      has a particular tropism for embryonic salivary gland and other head mesenchyme.
      CMV has evolved to co-opt cell signaling networks so to optimize replication and
      survival, to the detriment of infected tissues. It has been postulated that
      mesenchymal infection is the critical step in disrupting organogenesis. If so,
      organogenesis dependent on epithelial-mesenchymal interactions would be
      particularly vulnerable. In this study, we chose to model the vulnerability by
      investigating the cell and molecular pathogenesis of CMV infected mouse embryonic
      submandibular salivary glands (SMGs). RESULTS: We infected E15 SMG explants with
      mouse CMV (mCMV). Active infection for up to 12 days in vitro results in a
      remarkable cell and molecular pathology characterized by atypical ductal
      epithelial hyperplasia, apparent epitheliomesenchymal transformation, oncocytic
      like stromal metaplasia, beta-catenin nuclear localization, and upregulation of
      Nfkb2, Relb, Il6, Stat3, and Cox2. Rescue with an antiviral nucleoside analogue
      indicates that mCMV replication is necessary to initiate and maintain SMG
      dysmorphogenesis. CONCLUSION: mCMV infection of embryonic mouse explants results
      in dysplasia, metaplasia, and, possibly, anaplasia. The molecular pathogenesis
      appears to center around the activation of canonical and, perhaps more
      importantly, noncanonical NFkappaB. Further, COX-2 and IL-6 are important
      downstream effectors of embryopathology. At the cellular level, there appears to
      be a consequential interplay between the transformed SMG cells and the
      surrounding extracellular matrix, resulting in the nuclear translocation of beta
      catenin. From these studies, a tentative framework has emerged within which
      additional studies may be planned and performed.

PMID- 16959039
TI  - Local radiotherapeutic management of ependymomas with fractionated stereotactic
      radiotherapy (FSRT).
AB  - BACKGROUND: To assess the role of Fractionated Stereotactic Radiotherapy (FSRT)
      in the management of ependymomas. METHODS: From January 1992 to July 2003, FSRT
      was performed in 19 patients with histologically confirmed ependymomas. The
      median age was 15 years, 5 patients were younger than 4 years of age. Twelve
      patients received FSRT as primary postoperative radiotherapy after surgical
      resection. In 6 patients irradiation of the posterior fossa was performed with a
      local boost to the tumor bed, and in 4 patients the tumor bed only was
      irradiated. In 7 patients FSRT was performed as re-irradiation for tumor
      progression. This patient group was analyzed separately. A median dose of 54 Gy
      was prescribed in a median fractionation of 5 x 1.8 Gy per week for primary RT
      using 6 MeV photons with a linear accelerator. For FSRT as re-irradiation, a
      median dose of 36 Gy was applied. All recurrent tumors were localized within the
      former RT-field. RESULTS: The 5- and 10-year overall survival rates were 77% and
      64%, respectively. Patients treated with FSRT for primary irradiation showed an
      overall survival of 100% and 78% at 3 and 5 years after irradiation of the
      posterior fossa with a boost to the tumor bed, and a survival rate of 100% at 5
      years with RT of the tumor bed only. After re-irradiation with FSRT, survival
      rates of 83% and 50% at 3-and 5 years, respectively, were obtained.Progression
      free survival rates after primary RT as compared to re-irradiation were 64% and
      60% at 5 years, respectively.FSRT was well tolerated by all patients and could be
      completed without interruptions due to side effects. No severe treatment related
      toxicity > CTC grade 2 for patients treated with FSRT could be observed.
      CONCLUSION: The present analysis shows that FSRT is well tolerated and highly
      effective in the management of ependymal tumors. The rate of recurrences,
      especially at the field border, is not increased as compared to conventional
      radiotherapy consisting of craniospinal irradiation and a local boost to the
      posterior fossa.

PMID- 16959040
TI  - The catatonic dilemma expanded.
AB  - Catatonia is a common syndrome that was first described in the literature by Karl
      Kahlbaum in 1874. The literature is still developing and remains unclear on many
      issues, especially classification, diagnosis, and pathophysiology. Clinicians
      caring for psychiatric patients with catatonic syndromes continue to face many
      dilemmas in diagnosis and treatment. We discuss many of the common problems
      encountered in the care of a catatonic patient, and discuss each problem with a
      review of the literature. Focus is on practical aspects of classification,
      epidemiology, differential diagnosis, treatment, medical comorbidity, cognition,
      emotion, prognosis, and areas for future research in catatonic syndromes.

PMID- 16959041
TI  - Brief screening for co-occurring disorders among women entering substance abuse
      treatment.
AB  - BACKGROUND: Despite the importance of identifying co-occurring psychiatric
      disorders in substance abuse treatment programs, there are few appropriate and
      validated instruments available to substance abuse treatment staff to conduct
      brief screen for these conditions. This paper describes the development,
      implementation and validation of a brief screening instrument for mental health
      diagnoses and trauma among a diverse sample of Black, Hispanic and White women in
      substance abuse treatment. With input from clinicians and consumers, we adapted
      longer existing validated instruments into a 14 question screen covering
      demographics, mental health symptoms and physical and sexual violence exposure.
      All women entering treatment (methadone, residential and out-patient) at five
      treatment sites were screened at intake (N = 374). RESULTS: Eighty nine percent
      reported a history of interpersonal violence, and 70% reported a history of
      sexual assault. Eighty-eight percent reported mental health symptoms in the last
      30 days. The screening questions administered to 88 female clients were validated
      against in-depth psychiatric diagnostic assessments by trained mental health
      clinicians. We estimated measures of predictive validity, including sensitivity,
      specificity and predictive values positive and negative. Screening items were
      examined multiple ways to assess utility. The screen is a useful and valid proxy
      for PTSD but not for other mental illness. CONCLUSION: Substance abuse treatment
      programs should incorporate violence exposure questions into clinical use as a
      matter of policy. More work is needed to develop brief screening tools measures
      for front-line treatment staff to accurately assess other mental health needs of
      women entering substance abuse treatment.

PMID- 16959042
TI  - Identifying genes that contribute most to good classification in microarrays.
AB  - BACKGROUND: The goal of most microarray studies is either the identification of
      genes that are most differentially expressed or the creation of a good
      classification rule. The disadvantage of the former is that it ignores the
      importance of gene interactions; the disadvantage of the latter is that it often
      does not provide a sufficient focus for further investigation because many genes
      may be included by chance. Our strategy is to search for classification rules
      that perform well with few genes and, if they are found, identify genes that
      occur relatively frequently under multiple random validation (random splits into
      training and test samples). RESULTS: We analyzed data from four published studies
      related to cancer. For classification we used a filter with a nearest centroid
      rule that is easy to implement and has been previously shown to perform well. To
      comprehensively measure classification performance we used receiver operating
      characteristic curves. In the three data sets with good classification
      performance, the classification rules for 5 genes were only slightly worse than
      for 20 or 50 genes and somewhat better than for 1 gene. In two of these data
      sets, one or two genes had relatively high frequencies not noticeable with rules
      involving 20 or 50 genes: desmin for classifying colon cancer versus normal
      tissue; and zyxin and secretory granule proteoglycan genes for classifying two
      types of leukemia. CONCLUSION: Using multiple random validation, investigators
      should look for classification rules that perform well with few genes and select,
      for further study, genes with relatively high frequencies of occurrence in these
      classification rules.

PMID- 16959043
TI  - Phase distribution of spliceosomal introns: implications for intron origin.
AB  - BACKGROUND: The origin of spliceosomal introns is the central subject of the
      introns-early versus introns-late debate. The distribution of intron phases is
      non-uniform, with an excess of phase-0 introns. Introns-early explains this by
      speculating that a fraction of present-day introns were present between minigenes
      in the progenote and therefore must lie in phase-0. In contrast, introns-late
      predicts that the nonuniformity of intron phase distribution reflects the
      nonrandomness of intron insertions. RESULTS: In this paper, we tested the two
      theories using analyses of intron phase distribution. We inferred the evolution
      of intron phase distribution from a dataset of 684 gene orthologs from seven
      eukaryotes using a maximum likelihood method. We also tested whether the observed
      intron phase distributions from 10 eukaryotes can be explained by intron
      insertions on a genome-wide scale. In contrast to the prediction of introns
      early, the inferred evolution of intron phase distribution showed that the
      proportion of phase-0 introns increased over evolution. Consistent with introns
      late, the observed intron phase distributions matched those predicted by an
      intron insertion model quite well. CONCLUSION: Our results strongly support the
      introns-late hypothesis of the origin of spliceosomal introns.

PMID- 16959044
TI  - FAT10, a gene up-regulated in various cancers, is cell-cycle regulated.
AB  - BACKGROUND: FAT10 is a member of the ubiquitin-like-modifier family of proteins.
      Over-expression of the FAT10 gene was observed in the tumors of several
      epithelial cancers. High FAT10 expression was found to lead to increased
      chromosome instability via the reduction in the kinetochore localization of MAD2
      during the prometaphase stage of the cell-cycle. FAT10 expression was also
      previously reported to be regulated by cytokines and p53. RESULTS: Here, we
      report that FAT10 expression is regulated at the protein and transcript level
      during cell-cycle with highest expression observed during the S-phase of the cell
      cycle. The distal region between -1997 to -975 bp from the transcription start
      site of the FAT10 promoter may play a role in the repression of FAT10 expression
      during G2/M phase of the cell-cycle. CONCLUSION: FAT10 expression is regulated
      during cell-cycle.

PMID- 16959045
TI  - A comparison of decision-making by physicians and administrators in healthcare
      settings.
AB  - Physicians and administrators are committed to the same goal of providing quality
      care at affordable costs. Their perceptions of each other and their resulting
      behaviors, however, may lead to conflict. We offer some insight into these
      perceptions and behaviors, and provide a framework to improve communication and
      to reduce misunderstanding.

PMID- 16959046
TI  - Response to commentary by Dixon and Silman on the systematic review and meta
      analysis by Bongartz et al.

PMID- 16959047
TI  - Functional genomics of the yeast DNA-damage response.
AB  - High-throughput approaches are beginning to have an impact on many areas of yeast
      biology. Two recent studies, using different experimental platforms, provide
      insight into new pathways involved in the response of yeast to DNA damage.

PMID- 16959048
TI  - Pro/con debate: antifungal prophylaxis is important to prevent fungal infection
      in patients with acute necrotizing pancreatitis receiving broad-spectrum
      antibiotics.
AB  - When critically ill patients with pancreatitis develop infection of the pancreas,
      the ongoing management of such patients becomes difficult. Sufficient evidence
      supports the use of broad-spectrum antibiotic prophylaxis to prevent the
      development of bacterial infection. Since fungal infection is also a relatively
      common complication of severe pancreatitis--particularly when broad-spectrum
      antibiotics are used--it seems logical that fungal prophylaxis may be an
      important component of management. In this issue of Critical Care, two expert
      groups debate the merits of antifungal prophylaxis in patients with acute
      necrotizing pancreatitis who are receiving antibiotics.

PMID- 16959049
TI  - Serum uric acid, creatinine, and the assessment of antioxidant capacity in
      critical illness.

PMID- 16959050
TI  - Fluoride exposure inhibits protein expression and enzyme activity in the lung
      stage larvae of Ascaris suum.
AB  - Sodium fluoride (NaF) is an anion that has been previously shown to block the
      moulting process of Ascaris suum larvae. This study describes moulting and
      development-specific protein expression profiles of A. suum lung-stage L3 (AsLL3)
      following NaF exposure. AsLL3s cultured in the presence or absence of NaF were
      prepared for protein analysis using two-dimensional (2D) electrophoresis. NaF
      exposure inhibited at least 22 proteins in AsLL3 compared with moulted larvae
      (i.e. AsLL4). A further comparison of AsLL4 with those of pre-cultured AsLL3 and
      NaF-exposed AsLL3 revealed 8 stage-specifically and 4 over-expressed proteins.
      Immunoblot analysis revealed an inhibition by NaF of 19 immunoreactive proteins.
      Enzyme assay and immunochemical data showed an inhibition of the moulting
      specific inorganic pyrophosphatase activity by 41% and a decreased expression in
      NaF-treated larvae, indicating its significance in the moulting process. A
      protein spot associated with NaF inhibition was isolated and identified by
      peptide mass spectrometry and bioinformatics approaches to be a member of 3
      hydroxyacyl-CoA dehydrogenase/short-chain dehydrogenase enzyme families. These
      results have implications for the identification of proteins specific to the
      moulting process as potential chemotherapeutic targets.

PMID- 16959051
TI  - Molecular evidence for infection by HTLV-2 among individuals with negative
      serological screening tests for HTLV antibodies.
AB  - Previous serological studies on the Arara do Laranjal Indian group revealed
      extensive HTLV-2 infections. A collection of 97 new samples from the Arara were
      found repeatedly negative using three different commercial enzyme immunoassays.
      Eight samples that exhibited optical density readings close to the cut-off value
      were re-evaluated using Western blot (GeneLab 2.4, Singapore) assay. One sample
      was found to be non-reactive, five exhibited indeterminate patterns, one was
      classified as HTLV, and one was confirmed as HTLV-2. Peripheral blood mononuclear
      cell DNA of the eight samples were subjected to nested PCR and restriction
      fragment length polymorphism (RFLP) analysis of the pX and env regions, and
      nucleotide sequencing of the 5'-LTR region. All produced amplification products
      of pX, but env could be amplified in only one sample with the commonly used
      primers. RFLP analysis of the pX region using TaqI confirmed HTLV-2 infection.
      Nucleotide sequencing of the 5'-LTR region was performed in three samples (HTLV
      2, HTLV and indeterminate based on Western blot pattern). Phylogenetic analysis
      of a 449-nt fragment using the Neighbour-Joining method clearly demonstrated that
      the three samples clustered within the HTLV-2c molecular subtype. The present
      study confirms the wide dissemination of the HTLV-2c subtype among linguistically
      and culturally distinct Amazonian Indian groups, and emphasizes the unique
      occurrence of infection by this subtype in Brazil. Moreover, it emphasizes the
      limitation of employing the present serological screening assays in blood banks,
      epidemiological studies, and the importance of molecular assays in the
      confirmatory procedures for the primary detection of HTLV-2 infections.

PMID- 16959052
TI  - Bovine tuberculosis in southern African wildlife: a multi-species host-pathogen
      system.
AB  - This review examines the current situation of bovine tuberculosis (bTB) in
      southern African savannah systems, and uses theory on multi-species host-pathogen
      systems to suggest possible options for future research and management. In
      southern Africa, the buffalo (Syncerus caffer) and the Kafue lechwe [Marsh
      antelope] (Kobus leche) have been found to be maintenance hosts for this disease,
      but the importance of other host species is becoming apparent. The role of other
      host species in the maintenance and spread of the disease varies, depending on
      the spatial distribution and resource utilization patterns of the species,
      disease susceptibility, transmission modes and the ecology of both host(s) and
      vector(s). Future research needs to identify the pathogenicity of bTB in each of
      the host species, and the mechanisms and rates of inter- and intra-specific
      transmission among different species, in order to develop multi-host models to
      understand the development and spread of the disease.

PMID- 16959053
TI  - Epidemic influenza and vitamin D.
AB  - In 1981, R. Edgar Hope-Simpson proposed that a 'seasonal stimulus' intimately
      associated with solar radiation explained the remarkable seasonality of epidemic
      influenza. Solar radiation triggers robust seasonal vitamin D production in the
      skin; vitamin D deficiency is common in the winter, and activated vitamin D,
      1,25(OH)2D, a steroid hormone, has profound effects on human immunity. 1,25(OH)2D
      acts as an immune system modulator, preventing excessive expression of
      inflammatory cytokines and increasing the 'oxidative burst' potential of
      macrophages. Perhaps most importantly, it dramatically stimulates the expression
      of potent anti-microbial peptides, which exist in neutrophils, monocytes, natural
      killer cells, and in epithelial cells lining the respiratory tract where they
      play a major role in protecting the lung from infection. Volunteers inoculated
      with live attenuated influenza virus are more likely to develop fever and
      serological evidence of an immune response in the winter. Vitamin D deficiency
      predisposes children to respiratory infections. Ultraviolet radiation (either
      from artificial sources or from sunlight) reduces the incidence of viral
      respiratory infections, as does cod liver oil (which contains vitamin D). An
      interventional study showed that vitamin D reduces the incidence of respiratory
      infections in children. We conclude that vitamin D, or lack of it, may be Hope
      Simpson's 'seasonal stimulus'.

PMID- 16959054
TI  - Burden of paediatric invasive pneumococcal disease in Europe, 2005.
AB  - Within the European Union (EU), documenting the burden of invasive pneumococcal
      disease (IPD) in infants and children is important for coordinating effective
      pneumococcal immunization policies. Our objective was to document the burden of
      IPD in countries of the EU plus Switzerland and Norway. European affiliates of
      Wyeth Vaccines made available recent epidemiological data on IPD from local
      disease surveillance programmes, including unpublished sources. Recent literature
      and websites were also searched to provide as wide a representation as possible.
      This included OVID and abstracts from a number of international meetings, dating
      from the year 2000. The reported rates of paediatric IPD per 100000 (age) ranged
      from a low of 1.7 (<2 years) to 4.2 (2-15 years) in Sweden to a high of 93.5 to
      174 (<2 years) to 56.2 (<5 years) in Spain. The percentage of circulating
      serotypes causing IPD that are covered by 7-valent pneumococcal conjugate vaccine
      (PCV) IPD serotype coverage ranged from 60% to 80% for European children aged <2
      years. Under reporting, differences in reporting methods, antibiotic prescribing
      and disparities in blood-culturing practices may explain the differences in
      reported disease incidence. Because of the excellent clinical efficacy of the PCV
      against IPD, national pneumococcal vaccination programmes in Europe have the
      potential to prevent much morbidity and mortality.

PMID- 16959055
TI  - A randomized trial of low-frequency right-prefrontal-cortex transcranial magnetic
      stimulation as augmentation in treatment-resistant major depression.
AB  - Low-frequency right prefrontal repetitive transcranial magnetic stimulation
      (rTMS) appears to have antidepressant properties although the effectiveness of
      this treatment in clinical practice has not been assessed nor have the optimal
      stimulation parameters been adequately defined. A total of 130 patients with
      treatment-resistant depression were randomized to either 1- or 2-Hz rTMS over the
      right prefrontal cortex (PFC) for 2 wk with a possible further 2 wk extension.
      Non-responders were randomized to either 5- or 10-Hz left PFC rTMS. Overall, 66
      patients (51%) achieved response and 35 (27%) remission criteria. For right-sided
      treatment, depression significantly improved but there was no between-group
      difference. Twenty-eight (42%) patients in the 1-Hz group and 33 (53%) patients
      in the 2-Hz group achieved response criteria (chi2=1.40, p>0.05). Depression
      symptom scores also improved for patients who crossed over to left-sided
      treatment but there was no significant difference in response between 5- and 10
      Hz rTMS. Despite a heterogeneous sample, a significant proportion of patients met
      clinical response criteria following treatment but response to 1 and 2 Hz did not
      differ. 2-Hz right PFC rTMS has antidepressant properties but offers no advantage
      over 1 Hz despite doubling pulse number.

PMID- 16959056
TI  - Fluvoxamine, a selective serotonin reuptake inhibitor, and 5-HT2C receptor
      inactivation induce appetite-suppressing effects in mice via 5-HT1B receptors.
AB  - Serotonin (5-hydroxytryptamine; 5-HT) 2C receptors and the downstream
      melanocortin pathway are suggested to mediate the appetite-suppressing effects of
      5-HT drugs such as m-chlorophenylpiperazine (mCPP) and fenfluramine. Here, we
      report that fluvoxamine (3-30 mg/kg), a selective serotonin reuptake inhibitor
      (SSRI), in the presence of SB 242084 (1-2 mg/kg), a selective 5-HT2C receptor
      antagonist, exerts appetite-suppressing effects while fluvoxamine or SB 242084
      alone has no effect. The appetite-suppressing effects were attenuated in the
      presence of SB 224289 (5 mg/kg), a selective 5-HT1B receptor antagonist.
      Moreover, CP 94253 (5-10 mg/kg), a selective 5-HT1B receptor agonist, exerted
      appetite-suppressing effects and significantly increased hypothalamic pro
      opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART)
      gene expression and decreased hypothalamic orexin gene expression. These results
      suggest that fluvoxamine and inactivation of 5-HT2C receptors exert feeding
      suppression through activation of 5-HT1B receptors, and that 5-HT1B receptors up
      regulate hypothalamic POMC and CART gene expression and down-regulate
      hypothalamic orexin gene expression in mice.

PMID- 16959057
TI  - Association study of tardive dyskinesia and twelve DRD2 polymorphisms in
      schizophrenia patients.
AB  - Tardive dyskinesia (TD) is a side-effect of chronic antipsychotic medication.
      Abnormalities in dopaminergic activity in the nigrostriatal system have been most
      often suggested to be involved because the agents which cause TD share in common
      potent antagonism of dopamine D2 receptors (DRD2), that notably is not balanced
      by effects such as more potent serotonin (5-HT)2A antagonism. Thus, a number of
      studies have focused on the association of dopamine system gene polymorphisms and
      TD. The most consistent findings have been found with the Ser9Gly polymorphism of
      the DRD3 gene. Although DRD2 has long been hypothesized to be the main target for
      antipsychotics, only a few polymorphisms in DRD2 have been investigated for their
      potential involvement in the aetiology of TD. In the present study, we
      investigated 12 polymorphisms spanning the DRD2 gene and their association with
      TD in our European Caucasian (n=202) and African-American (n=30) samples.
      Genotype frequencies for a functional polymorphism, C957T (Duan et al., 2003;
      Hirvonen et al., 2004), and the adjacent C939T polymorphism were found to be
      significantly associated with TD (p=0.013 and p=0.022 respectively). DRD2
      genotypes were not significantly associated with TD severity as measured by AIMS
      (Abnormal Involuntary Movement Scale) with the exception of a trend for C939T
      (p=0.071). Both TD and total AIMS scores were found to be significantly
      associated with two-marker haplotypes containing C939T and C957T (p=0.021 and
      p=0.0087 respectively). Preliminary results indicated that C957T was also
      associated with TD in our African-American sample (p=0.047). Taken together, the
      present study suggests that DRD2 may be involved in TD in the Caucasian
      population, although further studies are warranted.

PMID- 16959058
TI  - Predicting post-traumatic stress disorder: validation of the Trauma Screening
      Questionnaire in victims of assault.
AB  - BACKGROUND: No accurate means of determining which individuals will develop post
      traumatic stress disorder (PTSD) following a traumatic event has yet been
      identified. This study aimed to determine the validity of the Trauma Screening
      Questionnaire (TSQ) in predicting the development of PTSD following assault.
      METHOD: Five hundred and sixty-two individuals who presented to an emergency unit
      following assault completed the TSQ between 1 and 3 weeks later. The Davidson
      Trauma Scale (DTS) was completed by the same individuals at 1 month and 6 months
      following assault to determine the presence of PTSD. The predictive power of the
      TSQ was determined by statistical tests. RESULTS: The TSQ was an effective means
      of predicting future PTSD, with a sensitivity of 0.85, specificity 0.89, negative
      predictive value (NPV) 0.98 and efficiency 0.90. The positive predictive value
      (PPV) was lower (0.48), probably as a result of the relatively low prevalence of
      PTSD at 1 month (11%) and 6 months (8%) following the assault. CONCLUSIONS: This
      study suggests that the TSQ can be used between 1 and 3 weeks after assault to
      help identify individuals who will develop PTSD.

PMID- 16959060
TI  - When ancient meets modern: the relationship between postpartum non-susceptibility
      and contraception in sub-Saharan Africa.
AB  - Extended durations of postpartum non-susceptibility (PPNS) comprising lactational
      amenorrhoea and associated taboos on sex have been a central component of
      traditional reproductive regimes in sub-Saharan Africa. In situations of rising
      contraceptive prevalence this paper draws on data from the Demographic Health
      Surveys to consider the neglected interface between ancient and modern methods of
      regulation. The analysis reports striking contrasts between countries. At one
      extreme a woman's natural susceptibility status appears to have little bearing on
      the decision to use contraception in Zimbabwe, with widespread 'double
      protection'. By contrast, contraceptive use in Kenya and Ghana builds directly
      onto underlying patterns of PPNS. Possible explanations for the differences and
      the implications for theory and policy are discussed.

PMID- 16959059
TI  - Aggressiveness, not impulsiveness or hostility, distinguishes suicide attempters
      with major depression.
AB  - BACKGROUND: Impulsiveness, hostility and aggressiveness are traits associated
      with suicidal behavior, but also with borderline personality disorder (BPD). The
      presence of large numbers of BPD subjects in past attempter samples may distort
      the relative importance of each of these traits to predicting suicidal behavior,
      and lead to prospective, biological and genetic models that systematically
      misclassify certain subpopulations of suicidal individuals. METHOD: Two hundred
      and seventy-five subjects with major depressive disorder (MDD), including 87 with
      co-morbid BPD (69 past suicide attempters, 18 non-attempters) and 188 without BPD
      (76 attempters, 112 non-attempters) completed standard impulsiveness, hostility
      and aggressiveness ratings. Differences between past suicide attempters and non
      attempters were examined with the sample stratified by BPD status. RESULTS: As
      expected, BPD subjects scored significantly higher than non-BPD subjects on all
      three trait measures. Stratifying by BPD status, however, eliminated
      attempter/non-attempter differences in impulsiveness and hostility in both
      patient subgroups. Past suicide attempters in each of the two subgroups of
      patients were only distinguished by higher levels of aggressiveness. CONCLUSIONS:
      Once BPD is accounted for, a history of aggressive behavior appears to be the
      distinguishing trait characteristic of suicide attempters with major depression,
      rather than global personality dimensions such as impulsiveness or hostility.
      Aggressiveness, and not these related traits, may be the ideal target for
      behavioral, genetic and biological research on suicidal behavior, as well as for
      the clinical assessment of suicide risk.

PMID- 16959061
TI  - Racial differences in the relationship between infant mortality and socioeconomic
      status.
AB  - This study presents an ecological analysis of the relationship between infant
      mortality and economic status by race in metropolitan Ohio, using census data on
      mother's residence and economic status determined by the percentage of low-income
      families living in each area. The analysis updates previous studies as white-non
      white comparisons for total infant mortality are examined for the US censuses of
      1960, 1970, 1980, 1990 and 2000; and more detailed period- and broad cause
      specific rates are presented for 2000. A pronounced inverse association is
      consistently found between income status and infant mortality for whites, while
      for non-whites this pattern first emerges in 1979-81, disappears during the 1980s
      and then returns more strongly during the 1990s. Similarly, the 2000 data reveal
      a consistent inverse pattern between income status and infant mortality for white
      and non-white neonatal and postneonatal death rates, as well as exogenous cause
      specific death rates. It is concluded that low-income whites and non-whites have
      infant mortality rates substantially higher than the overall rate for the
      population. Policy implications are discussed.

PMID- 16959062
TI  - Parental preference for sons and daughters in a Western industrial setting:
      evidence and implications.
AB  - This paper considers whether sex composition of existing children in Australian
      families is an important factor in parity progression. Using census data from
      1981, 1986, 1991, 1996 and 2001, women are linked with their co-resident
      children, allowing investigation of family sex composition and its changing
      impact over time on the propensity to have another child. The study finds that
      parents are much more likely to have a third and fourth birth if existing
      children are all of the same sex, indicating a strong preference for children of
      both sexes. This increased propensity has added around three per cent to the
      fertility of recent cohorts. The paper concludes with a discussion of the
      potential impact of sex-selection technologies on fertility. The authors argue
      that future widespread use of reliable sex-selection technologies might act to
      increase fertility in the short term, but would lead to a long-term reduction in
      fertility.

PMID- 16959063
TI  - Dysfunction of paracellin-1 by dephosphorylation in Dahl salt-sensitive
      hypertensive rats.
AB  - A high-salt diet reduced the levels of renal cAMP content and serine
      phosphorylated paracellin-1 in Dahl salt-sensitive hypertensive rats. In MDCK
      cells expressing paracellin-1, protein kinase A inhibitor reduced the serine
      phosphorylated paracellin-1 and transepithelial Mg(2+) transport, suggesting that
      a dephosphorylation of paracellin-1 induces the reduction of Mg(2+) reabsorption
      in salt-sensitive hypertension.

PMID- 16959064
TI  - Abstracts of the British Pharmaceutical Conference. 2005.

PMID- 16959122
TI  - Simultaneous determination of urinary metabolites of methoxypsoralens in human
      and Umbelliferae medicines by high-performance liquid chromatography.
AB  - A high-performance liquid chromatography method has been developed for the
      determination of coumarins and furocoumarins (psoralens). Nine coumarins and
      furocoumarins are separated simultaneously on a Hypersil C(8) (25 cm x 4.6-mm
      i.d.) column with a gradient of methanol and acetonitrile aqueous solution as
      mobile phase at 1.0 mL/min with two-channel UV-vis absorbance detection. The
      limits of detection are 0.366, 0.219, 0.317, 0.440, 0.536, 0.300, 0.531, 0.531,
      0.237, and 0.280 ng/mL for coumarin, 7-hydroxycoumarin, 7-methoxycoumarin,
      citropten (5,7-dimethoxycoumarin), 7-ethoxy-4-methylcoumarin, psoralen,
      xanthotoxin (8-methoxypsoralen), bergapten (5-methoxypsoralen), isopimpinellin
      (5,8-dimethoxypsoralen), and imperatorin (9-isopenteneoxypsoralen), respectively.
      Human urine is analyzed 1-6 days after ingestion of the oral Chinese medicines.
      This lead to the conclusion that the concentration of coumarins and furocoumarins
      is higher than that of the control urine. The coumarins and furocoumarins are
      detected at 312 and 249 nm, respectively.

PMID- 16959123
TI  - Plasma protein fractions in healthy blood donors quantitated by an automated
      multicapillary electrophoresis system.
AB  - During the last decade, capillary electrophoresis (CE) has emerged as an
      important alternative to traditional analysis of serum and plasma proteins by
      agarose or celluloseacetate electrophoresis. CE analysis of plasma proteins can
      now be fully automated and also includes bar-code identification of samples,
      preseparation steps, and direct post-separation quantitation of individual peaks,
      which permits short assay times and high throughput. For laboratory work, it is
      important to have reference values from healthy individuals. Therefore, plasma
      samples from 156 healthy blood donors (79 females and 77 males) have been
      analyzed with the Capillarys instrument and the new high resolution buffer, which
      yields higher resolution than the beta1-beta2+ buffer. Albumin concentrations in
      samples are measured using nephelometry in order to assign protein concentrations
      to each peak. The 2.5 and 97.5 percentiles for both the percentages of different
      peaks and the protein concentrations in the peaks are calculated according to the
      recommendations of the International Federation of Clinical Chemistry on the
      statistical treatment of reference values. The Capillarys instrument is a
      reliable system for plasma protein analysis, combining advantages of full
      automation with high analytical performances and throughput.

PMID- 16959124
TI  - Solid-phase microextraction of organophosphate pesticides in source waters for
      drinking water treatment facilities.
AB  - The rapid detection of contaminants in our nation's drinking water has become a
      top homeland security priority in this time of increased national vigilance. Real
      time monitoring of drinking water for deliberate or accidental contamination is
      key to national security. One method that can be employed for the rapid screening
      of pollutants in water is solid-phase microextraction (SPME). SPME is a rapid,
      sensitive, solvent-free system that can be used to screen for contaminants that
      have been accidentally or intentionally introduced into a water system. A method
      using SPME has been developed and optimized for the detection of seven
      organophosphate pesticides in drinking water treatment facility source waters.
      The method is tested in source waters for drinking water treatment facilities in
      Mississippi and Alabama. Water is collected from a deepwater well at Stennis
      Space Center (SSC), MS, the drinking water source for SSC, and from the Converse
      Reservoir, the main drinking water supply for Mobile, AL. Also tested are samples
      of water collected from the Mobile Alabama Water and Sewer System drinking water
      treatment plant prior to chlorination. The method limits of detection for the
      seven organophosphates were comparable to those described in several
      Environmental Protection Agency standard methods. They range from 0.25 to 0.94
      microg/L.

PMID- 16959125
TI  - Comparison of analytical strategies for the chromatographic and mass
      spectrometric measurement of brominated flame retardants: 1. Polybrominated
      diphenylethers.
AB  - The chromatographic and mass spectrometric (MS) behaviors of 49 polybrominated
      diphenylether (PBDE) homologues toward various techniques is investigated.
      Special attention is paid to chromatographic separation, ionization processes,
      and signal acquisition modes. Different liquid chromatographic (LC) separation
      systems and gas chromatographic (GC) temperature program parameters are studied.
      For LC-MS experiments, the ionization efficiencies of electrospray, atmospheric
      pressure chemical ionization, and atmospheric pressure photoionization (APPI) are
      evaluated. For GC-MS experiments, negative chemical ionization with ammonia as
      reagent gas as well as negative and positive electron impact (EI) ionization are
      studied. Thus, fragmentation pathways of PBDEs are investigated, with the main
      objective being to determine the sensitivity/specificity balance of each tested
      technique with respect to their potential respective application (parent compound
      focusing, metabolite identification, and screening of analogue compounds).
      Finally, performances of the different tested techniques are compared and
      evaluated in terms of detection limits on standard solutions for each homologue
      group. In terms of ionization, EI remains the best compromise between sensitivity
      and specificity with possible complementary applications in MS-MS and high
      resolution MS. Nevertheless, APPI appears to be a promising alternative.

PMID- 16959126
TI  - Separating DDTs in edible animal fats using matrix solid-phase dispersion
      extraction with activated carbon filter, Toyobo-KF.
AB  - A technique is presented for the economical, routine, and quantitative analysis
      of contamination by dichloro-diphenyl-trichloroethanes (DDTs) [pp'-DDT, pp'
      dichlorodiphenyl dichloroethylene, and pp'-dichlorodiphenyl dichloreothane in
      beef tallow and chicken fat samples, based on their separation using matrix solid
      phase dispersion (MSPD) extraction with Toyobo-KF, an activated carbon fiber.
      Toyobo-KF is a newly applied MSPD sorbent, and it is followed by reversed-phase
      high-performance liquid chromatography (HPLC) with a photodiode array detector.
      The resulting analytical performance parameters [recoveries of spiked DDTs (0.1,
      0.2, and 0.4 microg/g) > or = 81%, with relative standard deviations of < or = 8%
      (n = 5), and quantitation limits < or = 0.03 microg/g], with minimal handling and
      cost-efficiency, indicate that the present MSPD-HPLC method may be a useful tool
      for routine monitoring of DDT contamination in meat.

PMID- 16959127
TI  - Quantitative determination of four constituents of Tinospora sps. by a reversed
      phase HPLC-UV-DAD method. Broad-based studies revealing variation in content of
      four secondary metabolites in the plant from different eco-geographical regions
      of India.
AB  - This paper describes the separation and quantitation of important markers, such
      as 20beta-hydroxyecdysone, tinosporaside, cordioside, and columbin, present in
      three species of Tinospora viz, T. cordifolia, T. malabrica, and T. crispa. A
      reverse-phase (RP) high-performance liquid chromatography (HPLC)-UV-diode array
      detection (DAD) method employing gradient elution is thus developed. The marker
      compounds isolated from 70% ethanolic extract of T. cordfolia by repeated column
      chromatography are identified on the basis of (1)H NMR, (13)C NMR, and mass
      spectral data. The compounds are separated on a RP (RP-18, 5 microm, 250 x 4.6-mm
      i.d.) column using water-acetonitrile gradient and are detected by the HPLC-UV
      DAD method. The calibration curves that result from marker compounds in the
      concentration range of 100-2000 ng on column exhibit a good correlation (r(2) >
      or = 0.99978). The method is successfully applied to separate and study the
      content of four marker compounds in 40 different accessions of three Tinospora
      species collected from different regions of India. The studies reveal that the
      maximum amount of the marker compounds is present in Tinospora cordifolia
      species, especially from accessions collected from higher altitudes of the Jammu
      province (North India).

PMID- 16959128
TI  - Two-dimensional thin-layer chromatography of selected coumarins.
AB  - Polar-bonded stationary phases (CN-silica and Diol-silica) are used with
      nonaqueous eluents in adsorption mode or with aqueous eluents in partition mode.
      This enables the application of these systems in two-dimensional separations
      because of the different selectivity and application to the separation of closely
      related compounds of similar physicochemical properties and retention behaviour.
      Similarly, multiphase plates, connected with C18 strips and silica layers, are
      used with aqueous and nonaqueous eluents. Such layers were applied for the
      separation of selected coumarins. Thus, differences in separation selectivity are
      applied for the separation of coumarin fractions from plant extracts of the
      Apiaceae family by two-dimensional thin-layer chromatography.

PMID- 16959129
TI  - Multiresidue analysis of 18 organochlorine pesticides in traditional chinese
      medicine.
AB  - A simple and efficient method for simultaneous gas chromatographic (GC)
      determination of 18 organochlorine pesticides [tecnazene, hexachlorobenzene,
      alpha-benzenehexachloride (BHC), pentachloronitrobenzene (PCNB), gamma-BHC,
      heptachlor, aldrin, methyl pentachlorophenyl sulfide, beta-BHC, delta-BHC,
      heptachlor epoxide, alpha-endosulfan, trans-chlorodane, cis-chlorodane, p,p'
      dichlorodiphenyl dichloroethylene, o,p'-DDT, p,p'-DDD, and p,p'-DDT] in
      Traditional Chinese Medicine (TCM) is described. The procedure involves
      ultrasonic extraction and sulphuric acid treatment as the cleanup method.
      Detection of the sample is performed by GC-electron capture detection. A series
      of experiments are conducted to optimize the final pretreatment conditions
      [acetone-petroleum ether (1:1) as the extract solvent, ultrasonication for 15
      min, three steps, concentrated sulphuric acid with 10% water for sulphuric acid
      treatment]. Recovery studies are performed at 10, 50, and 100 parts-per-billion
      (ppb) fortification levels of each organochlorine pesticide, except for alpha
      endosulfan, which are 20, 100, and 200 ppb. The percentage recoveries range from
      77.9% +/- 6.4% to 114.0% +/- 8.1% (average +/- standard deviation). The simple
      and rapid method may be used to routinely determine organochlorine pesticides in
      TCM.

PMID- 16959130
TI  - Subcritical solvent regeneration of contaminated HPLC columns used for separating
      biomolecules.
AB  - The regeneration of contaminated chromatography columns using subcritical mobile
      phases is presented. The method employs minimal amounts of organic solvents
      (pressurized and heated above their boiling point) to clean strongly retained
      sample components from hydrophobic stationary phase particles. The process lasts
      approximately 1 h and is demonstrated to restore the performance of polymeric and
      bonded-phase columns. The technique is simple to apply and widely accessible,
      requiring only common laboratory equipment. Results indicate that this could be a
      beneficial alternative approach for cleaning contaminated columns either directly
      or in cases in which conventional methods have been unsuccessful.

PMID- 16959131
TI  - Analytical procedure for the determination of the marijuana metabolite 11-nor
      Delta9-tetrahydrocannabinol-9-carboxylic acid in oral fluid specimens.
AB  - The determination of the marijuana metabolite 11-nor-Delta(9)
      tetrahydrocannabinol-9-carboxylic acid (THCA) in oral fluid specimens is
      described for the first time using a Quantisal oral fluid collection device and
      gas chromatography with single-quadrupole mass spectrometric detection. Oral
      fluid specimens were confirmed for the presence of THCA using two-dimensional gas
      chromatography-mass spectrometry in order to achieve the low concentration levels
      previously reported to be present in oral fluid. The extraction efficiency for
      THCA from the oral fluid collection pad was determined to be 80% at a
      concentration of 10 pg/mL with a coefficient of variation of 8.23%. The intraday
      precision of the assay ranged from 3.4% to 7.9% over four concentrations; the
      interday precision ranged from 8.3% to 18.5%. The limit of quantitation was 2
      pg/mL. The method was applied to oral fluid specimens collected from a frequent
      user of marijuana. Samples were collected almost immediately after the subject
      smoked and then at intervals of 15 and 45 min and 1, 2, and 8 h after smoking.
      THCA was present in all the specimens, even the initial specimen taken almost
      immediately after smoking. The presence of THCA minimizes the argument for
      passive exposure to marijuana in drug-testing cases.

PMID- 16959132
TI  - Detection of the marijuana metabolite 11-nor-Delta9-tetrahydrocannabinol-9
      carboxylic acid in oral fluid specimens and its contribution to positive results
      in screening assays.
AB  - The detection of the marijuana metabolite 11-nor-Delta(9)-tetrahydrocannabinol-9
      carboxylic acid (THC-COOH) in oral fluid specimens is described, and its
      contribution to an immunoassay for the detection of cannabinoids is investigated.
      Oral fluid specimens, screened using an enzyme-linked immunosorbent immunoassay
      (ELISA), were carried forward to confirmation for both tetrahydrocannabinol (THC)
      and THC-COOH using gas chromatography-mass spectrometry (GC-MS). One hundred and
      fifty-three specimens were analyzed, of which 143 screened positive for
      cannabinoids. Ninety-five (66.4%) of these specimens were positive for both THC
      and THC-COOH; 14 (9.7%) were positive for THC-COOH only, and 27 (18.8%) were
      positive for THC only. The GC-MS assay for the detection of THC-COOH in oral
      fluid was linear to 160 pg/mL with a limit of quantitation of 2 pg/mL. The
      detection of the marijuana metabolite, THC-COOH, in 76.2% of oral fluid specimens
      screening positive for cannabinoids is reported. As a potential defense against
      passive exposure claims, proposed SAMHSA regulations may require the simultaneous
      collection of a urine sample when oral fluid samples are used. The detection of
      the metabolite, THC-COOH, is a significant alternative to this approach because
      its presence in oral fluid minimizes the argument for passive exposure to
      marijuana in drug testing cases.

PMID- 16959133
TI  - Postmortem redistribution of two antipsychotic drugs, haloperidol and
      thioridazine, in the rat.
AB  - Antipsychotic drugs may be associated with arrhythmia, ventricular fibrillation,
      or torsades de pointes, which can result in sudden death. These drugs could
      therefore be found in postmortem toxicological analyses of autopsy specimens
      following unexplained sudden death. The drug concentrations in tissues and body
      fluids change between the death and postmortem specimens collection because of
      postmortem redistribution. For this reason, it is often difficult to interpret
      the postmortem analysis. The aim of this study was to investigate postmortem
      redistribution of the two cardiotoxic antipsychotic drugs, haloperidol and
      thioridazine, in order to interpret the postmortem analysis. We have chosen the
      rat as an animal model. The rats received 1 mg/kg of haloperidol and 5 mg/kg of
      thioridazine by intraperitoneal injection. They were sacrificed and left at room
      temperature for 2, 6, 12, 24, or 48 h, at which times blood and tissue samples
      were taken. The drug analyses in tissues and blood were done using a liquid
      chromatography- tandem mass spectrometry method. Our results show that there is a
      redistribution of the two drugs from the lung to the cardiac blood. The
      concentration of the antipsychotic drugs in the lung decreased rapidly, whereas
      in the cardiac blood, this concentration increased within the first 2 h
      postmortem. By 48 h after death, the concentrations of the antipsychotic drugs
      were about twice as high as the initial concentrations in the cardiac blood. For
      the lungs, a decrease of 50% was observed between 0 and 48 h. Only myocardium and
      muscle concentrations did not change with the postmortem delay.

PMID- 16959134
TI  - Hidden aconite poisoning: identification of yunaconitine and related aconitum
      alkaloids in urine by liquid chromatography-tandem mass spectrometry.
AB  - Poisoning from aconite occurs worldwide as a result of misuse of the potent
      plant. Laboratory investigation into suspected intoxication cases is challenging
      because the content of toxic aconitum alkaloids varies depending on the plant
      source, market processing, dosing protocol, hydrolytic degradation, and metabolic
      transformation. Using a triple-quadrupole tandem mass spectrometer, a group
      screening method was developed based on the mass-fragmentographic scheme of
      common aconitum alkaloids. The precursor-ion scans of m/z 105 and 135 permitted
      selective profiling of 14-O-benzoyl-norditerpenoids and the 14-O-anisoyl
      norditerpenoids, respectively. Gradient reversed-phase liquid chromatography
      minimized coelution of isobaric compounds. The screening protocol was applied to
      a clinical investigation of suspected herbal poisoning. In total, 15 urine
      samples were thus screened positive for aconitum alkaloid over 5 years. The
      diagnoses of aconite poisoning in 11 patients were firmly established based on
      the known prescription history and the positive urine finding. In four patients,
      without aconitum herbs being listed in the herbal prescriptions, contamination of
      the herbal remedies by aconite was suspected to be the hidden cause of their
      acute poisoning. Yunaconitne, a highly toxic aconitum alkaloid, was thus
      identified in human urine for the first time. The group screening method of
      aconitum alkaloids in urine is an important diagnostic aid for acute poisoning by
      aconites of an unclear origin.

PMID- 16959135
TI  - Distribution of ibogaine and noribogaine in a man following a poisoning involving
      root bark of the Tabernanthe iboga shrub.
AB  - In the present paper, we report for the first time the tissue distribution of
      ibogaine and noribogaine, the main metabolite of ibogaine, in a 48-year-old
      Caucasian male, with a history of drug abuse, found dead at his home after a
      poisoning involving the ingestion of root bark from the shrub Tabernanthe iboga.
      Ibogaine and noribogaine were quantified in tissues and fluids using a fully
      validated liquid chromatography-electrospray mass spectrometry method. Apart from
      cardiac tissue, ibogaine and noribogaine were identified in all matrices
      investigated. The highest concentrations were found in spleen, liver, brain, and
      lung. The tissue/subclavian blood concentration ratios averaged 1.78, 3.75, 1.16,
      and 4.64 for ibogaine and 0.83, 2.43, 0.90, and 2.69 for noribogaine for spleen,
      liver, brain, and lung, respectively. Very low concentrations of the two drugs
      were found in the prostatic tissue. Both ibogaine and noribogaine are secreted in
      the bile and cross the blood-brain barrier. Four other compounds were detected in
      most of the studied matrices. One of them was identified as ibogamine.
      Unfortunately, we were not able to positively identify the other three compounds
      because of the unavailability of reference substances. Two of them could possibly
      be attributed to the following oxidation products: iboluteine and
      desmethoxyiboluteine. The third compound could be ibogaline.

PMID- 16959136
TI  - Detection of benzodiazepines in hair using ELISA and LC-ESI-MS-MS.
AB  - This study was designed to validate an enzyme-linked immunosorbent assay (ELISA)
      and liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for the
      detection of nine benzodiazepines in hair. Sixteen hair case samples were tested
      from drug-related deaths where a positive benzodiazepine blood result was
      obtained. The case samples were decontaminated with 0.1% sodium dodecyl sulfate,
      distilled water, and dichloromethane. For ELISA analysis, the samples were
      extracted by incubation in monobasic phosphate buffer for 1 h and then
      neutralized with dibasic phosphate buffer. They were diluted 1:5 with phosphate
      buffer saline (PBS) prior to analysis. For LC-MS-MS, the samples were incubated
      overnight in methanol/25% ammonium hydroxide (20:1). The benzodiazepines were
      extracted by solid phase. Thirteen samples were confirmed positive by LC-MS-MS.
      The benzodiazepines detected included diazepam, nordiazepam, temazepam, oxazepam,
      nitrazepam, and lorazepam. Using a cut-off concentration of 0.1 ng/mg oxazepam,
      the Immunalysis Benzodiazepine Microplate ELISA demonstrated a sensitivity and
      specificity of 100% and 81%, respectively, compared with LC-MS-MS results.

PMID- 16959137
TI  - An unusual case of drug-facilitated sexual assault using aromatic solvents.
AB  - This report documents a case of drug-facilitated sexual assault (DFSA) under the
      influence of solvents. The victim was a 13-year-old female. Upon contact with law
      enforcement, she was still confused and could hardly explain the facts. She told
      authorities that she had been kidnapped 4 h previously when two individuals with
      covered faces put a cloth soaked in a solvent over her mouth. She spent a few
      hours in a room, during which she lost consciousness. The girl awakened semi-nude
      in the street with memory loss. No alcohol was present in the subject's body; no
      odor of alcohol was detected on the subject's breath. No lesions were observed
      during a gynecological exam. A blood sample was taken with the intent to
      investigate the use of chloroform or similar anesthetics. Toxicological analysis
      of the victim's blood revealed the presence of 7.6 mg/L of benzene, 24.8 mg/L of
      toluene, and 0.6 mg/L of xylene (mixture of isomers). As for other analytical
      findings, diazepam (0.02 mg/L) was also found. The aromatic solvents involved in
      this case were detected using gas chromatography with flame-ionization detection
      (GC-FID) and confirmed using GC-mass spectrometry (MS) in full scan mode after
      liquid-liquid extraction of the whole blood sample. Quantitation of the aromatic
      solvents was carried out using GC-FID. Diazepam was detected using GC with
      nitrogen-phosphorus detection (NPD) and confirmed using GC-MS with full scan mode
      after solid-phase extraction of the whole blood sample using Bond-Elut Certify
      columns. Quantitation of diazepam was carried out using GC-NPD. No other drugs,
      including ethanol, were detected. Recoveries for benzene, toluene, and xylene
      (mixture of isomers) in whole blood at 5 mg/L were 89.2%, 90.8%, and 93.4%,
      respectively. Intraday precisions were 5.3%, 5.0%, and 4.9%, respectively, and
      interday precisions were 12.1%, 11.6%, and 11.5%, respectively. The limits of
      detection (LOD) and quantitation (LOQ) were 30 and 100 microg/L, respectively.
      The linearity of the blood calibration curves was excellent with r(2) values of >
      0.999 (range 0.1-10 mg/L). Recovery for diazepam in whole blood at 0.5 mg/L was
      88.2% with intraday and interday precisions of 2.0% and 10.8%, respectively. The
      LOD and LOQ were 6 and 20 microg/L, respectively. The linearity of the blood
      calibration curve was excellent with r(2) values of > 0.999 (range 0.1-2 mg/L).
      We want to alert other toxicologists about new or unexpected products that should
      be taken into account when the surreptitious use of substances in DFSA is
      suspected.

PMID- 16959138
TI  - Testing for atropine and scopolamine in hair by LC-MS-MS after Datura inoxia
      abuse.
AB  - Datura inoxia belongs to the family of Solanaceae. This is a very common plant in
      New Caledonia that contains two main toxic alkaloids, l-atropine and l
      scopolamine. In this study, we report the case of a 20-year-old male admitted to
      an Emergency Unit after consumption of 6 dried flowers in hot water for
      hallucinations, mydriasis, and agitation associated with tachycardia and increase
      of systolic blood pressure to 180. Full recovery was observed after one week.
      Three weeks later, a lock of about 80 hairs (200 mg) was collected from the
      subject in vertex posterior with scissors to be tested for both atropine and
      scopolamine. After decontamination with dichloromethane, a strand of hair was
      segmented into three parts, cut into small segments (< 1 mm), incubated overnight
      in 1 mL pH 8.4 phosphate buffer in the presence of 2.5 ng atropine-d(3), the
      internal standard, then extracted with 5 mL dichloromethane/isopropanol/n-heptane
      (50:17:33). The residue was reconstituted in 100 microL of methanol, from which
      10 microL was injected into an XTerra MS C18 column (100 x 2.1 mm, 3.5 microm)
      eluted with a gradient of acetonitrile and formate buffer delivered at a flow
      rate of 0.2 mL/min. A Quattro Micro triple-quadrupole mass spectrometer (MS) was
      used for analyses. Ionization was achieved using electrospray in the positive
      ionization mode. For each compound, detection was related to two daughter ions
      (atropine: m/z 290.2 to 124.0 and 92.9; atropine-d(3): m/z 293.1 to 127.0 and
      92.9; scopolamine: m/z 304.1 to 138.0 and 156.0). Although atropine was never
      detected (limit of detection = 2 pg/mg), scopolamine was identified in the three
      segments, in the range 14 to 48 pg/mg. The absence of atropine in hair is
      consistent with its very low dosage in the flower of Datura inoxia. Hair
      segmentation indicated that the subject was previously exposed on several
      occasions to the plant. Liquid chromatography-tandem MS appears to be a necessity
      for testing tropane alkaloids of the Datura group, given the low concentrations
      to be measured.

PMID- 16959139
TI  - Effect of repeated cocaine administration on detection times in oral fluid and
      urine.
AB  - Detection times reported for single-dose studies may not predict detection times
      following repeated cocaine dosing. Although repeated cocaine administration can
      result in drug accumulation and extended excretion time, there is a paucity of
      data from controlled dosing studies with repeated drug administration. We
      compared detection times for cocaine and benzoylecgonine (BZE) in oral fluid and
      BZE in urine following single and repeated cocaine dosing. Two groups of cocaine
      experienced subjects participated in these studies. The single-dose group
      received cocaine by intravenous, intranasal, and smoked administration. The
      repeated dose group received daily escalating oral cocaine doses culminating in a
      total of 1,250-2,000 mg. Oral fluid and urine specimens following the last dosing
      were analyzed by gas chromatography-mass spectrometry. Detection times were
      determined as the time to the last positive specimen. The effect of repeated
      dosing was to extend oral fluid detection times for cocaine approximately
      fourfold and BZE detection times sevenfold, whereas urine BZE detection times
      were extended twofold. Because cocaine abusers frequently self-administer higher
      and repeated doses, we conclude that the short detection times observed in single
      dose studies underestimate the utility of oral fluid for detection of cocaine
      abuse in realistic settings.

PMID- 16959140
TI  - Enantiomeric determination of tramadol and O-desmethyltramadol by liquid
      chromatography- mass spectrometry and application to postoperative patients
      receiving tramadol.
AB  - A liquid chromatographic-mass spectrometric assay with atmospheric pressure
      chemical ionization is presented for quantification (selected-ion mode) of
      tramadol (T) and O-desmethyltramadol (ODT) in blood plasma after liquid-liquid
      extraction. The enantiomeric separation was achieved on a Chiralpak AD column
      containing amylose tris-(3,5-dimethylphenylcarbamate) as chiral selector. The
      validation data were within acceptable limits. The assay was successfully applied
      to authentic plasma samples allowing confirmation of diagnosis of overdose or
      intoxication as well as monitoring of patients' compliance. In postoperative
      patients receiving T, mean therapeutic plasma concentrations were determined as
      follows: 422.8 and 440.8 ng/mL for (+)-T and (-)-T, respectively, and 23.7 and
      40.7 ng/mL for (+)-ODT and (-)-ODT, respectively. Quantitative results
      demonstrated a great interindividual variability in postoperative plasma
      analgesic drug concentrations and, therefore, a wide therapeutic concentration
      range. The 7.7% of the samples that revealed negative results for ODT are likely
      explained by genetic polymorphisms resulting in absent enzyme activity of CYP2D6.

PMID- 16959141
TI  - Rapid screening for and simultaneous semiquantitative analysis of thirty abused
      drugs in human urine samples using gas chromatography-mass spectrometry.
AB  - In Japan, a wide variety of designer drugs became popular among juveniles because
      of their availability via the Internet and mobile phones. Hence, it is necessary
      to develop simple and rapid screening method for these drugs. We devised a rapid
      screening method for and simultaneous semiquantitative analysis of 30 abused
      drugs, including amphetamines, amphetamine-, piperazine-, tryptamine-, and
      phenethylamine-derived designer drugs and opiates in human urine. The urine
      sample was digested with urease, and the drugs were analyzed by gas
      chromatography-mass spectrometry in the scan mode after solid-phase extraction
      with a Focus column and acetylation. The retention time obtained with the use of
      a retention time locking technique and three qualifier ions were used to obtain
      positive results. As the Focus column requires only simple extraction steps and
      can retain various drugs of a wide range of polarity, screening of 30 abused
      drugs was feasible within 3 h. The calibration curves were linear in the
      concentration range of 100-5,000 ng/mL in most drugs with correlation
      coefficients exceeding 0.99. The absolute recoveries for all drugs in urine
      samples were 6.9-125.4% at the concentration 1,000 ng/mL. This method will be
      most useful to confirm the presence of many abused drugs in urine in clinical and
      forensic cases.

PMID- 16959142
TI  - Comparison of urine and oral fluid as matrices for screening of thirty-three
      benzodiazepines and benzodiazepine-like substances using immunoassay and LC-MS(
      MS).
AB  - Benzodiazepines are the most frequently detected medicinal drugs in drivers. The
      use of benzodiazepines is associated with an increased road accident risk. In
      this study, the presence of benzodiazepines detected by liquid chromatography
      (tandem) mass spectrometry [LC-MS(-MS)] in oral fluid and urine samples obtained
      from drivers stopped during a roadside survey was compared. In addition, the
      sensitivity and selectivity of enzyme multiplied immunoassay technique (EMIT II
      Plus) relative to LC-MS(-MS) was determined for both matrices. A total number of
      1,011 urine samples were collected and screened for benzodiazepines using
      immunoassay (IA) (EMIT II Plus; cutoff 300 ng/mL). In the IA-positive (n = 25)
      and a group of randomly selected negative urine samples (n = 79), the presence or
      absence of benzodiazepines was confirmed by LC-MS-MS after deglucuronidation. The
      corresponding oral fluid samples (n = 101, 3 samples omitted), were analyzed by
      LC-MS(-MS) and IA (EMIT II Plus; cutoff 10 ng/mL). The presence of
      benzodiazepines was demonstrated by LC-MS-(MS) in all IA-positive urine samples,
      but in only four corresponding oral fluid samples. Concentrations in oral fluid
      were, one substance excepted, lower than in urine. The sensitivity and
      specificity of EMIT II Plus were better by using urine as matrix for screening of
      benzodiazepines than by using oral fluid. The results show that benzodiazepines
      are detectable in oral fluid. More research has to be done to determine the
      pharmacokinetic profile of the different benzodiazepines in oral fluid and to
      study the relationship between dose, concentration (in oral fluid and blood), and
      impairment.

PMID- 16959143
TI  - [A noticeable renewal of shock resuscitation strategy].

PMID- 16959144
TI  - [New concepts of fluid management in liver transplant recipients].

PMID- 16959145
TI  - [Role of arterial myo-endothelial gap junction on the vascular contractile
      reactivity following hemorrhagic shock in rats].
AB  - OBJECTIVE: To observe the role of arterial myo-endothelial gap junction (MEGJ) on
      endothelium-dependent and independent vascular contractile reactivity following
      hemorrhagic shock in rats. METHODS: Fifty-six SD rats were randomly divided into
      noradrenaline (NE) group and myricetin group. NE group was further divided into 5
      subgroups: normal control group, 0, 0.5, 1 and 2 hours after hemorrhagic shock
      groups. Myricetin group was further divided into 7 subgroups: normal control
      group, 0, 0.5, 1, 2, 3 and 4 hours after hemorrhagic shock groups. Superior
      messenteric artery (SMA) was used to compare the changes in vascular responsing
      to NE or myricetin with or without 18alpha-glycyrrhetinic acid (18alpha-GA).
      RESULTS: Compared with normal control group, the reactivity of SMA rings to NE
      was significantly increased at 0 and 0.5 hour after shock and then decreased at 1
      hour and 2 hours after shock. 18alpha-GA had no effect on SMA constriction
      induced by NE. The reactivity of SMA rings to myricetin was increased at 0, 0.5,
      1 hour and 2 hours after shock, and it reached the peak at 2 hours, then it
      significantly decreased at 3 hours and 4 hours after shock. 18alpha-GA
      antagonized SMA constriction induced by myricetin. The antagonizing effect on
      myricetin in shock 1, 2 and 3 hours groups was more obvious than that in the
      other groups. CONCLUSION: At the early stage after hemorrhagic shock, the
      endothelium-dependent and independent vascular contractile response show a
      compensatory increase. The endothelium-independent contractile response is
      significantly decreased at 1 hour and 2 hours after shock, and the endothelium
      dependent contractile response is significantly decreased at 3 hours and 4 hours
      after shock. MEGJ plays an important role in endothelium-dependent vascular
      contractile reactivity following hemorrhagic shock.

PMID- 16959146
TI  - [Heterogeneity changes in secretion ability of monocyte/macrophage and its
      significance after trauma hemorrhage in rat].
AB  - OBJECTIVE: To investigate the relationship between the heterogeneity in secretion
      ability of monocyte (Mo)/macrophage and the immune dysfunction after severe
      trauma. METHODS: Twenty-four healthy Wistar rats were randomly divided into
      normal control group and trauma hemorrhage 1, 4 and 7 days groups. The contents
      of interleukin-6 (IL-6) and IL-10 secretion of Mo/macrophage from different
      anatomical regions were determined by radioimmunoassay. RESULTS: (1)In normal
      rats, the ability to secrete IL-6 and IL-10 was different among alveolar
      macrophages (AM), peritoneal macrophages (PM) and Mo. PM showed the highest
      ability to secrete IL-10 while Mo had the highest ability to secrete IL-6.
      (2)After trauma hemorrhage, the secretion of IL-6 and IL-10 by AM were increased
      dramatically. On the contrary, the secretion of IL-6 by PM was declined from the
      1st day to the 4th day, then increased even over that of the normal control group
      on the 7th day. However, the secretion of IL-10 by PM was significantly elevated
      on the 1st day after trauma hemorrhage, peaking on the 4th day, and only slight
      lowering was found on the 7th day. The secretion of IL-6 by Mo was declined
      gradually all the time, reaching the lowest point on the 7th day. On the
      contrary, the secretion of IL-10 by Mo was increasing, reaching its peak on the
      7th day. CONCLUSION: The heterogeneity of secretion ability of Mo/macrophage
      obtained from different anatomical regions is present under normal condition, and
      is more obvious following a severe injury. This change may play an important role
      in the immune dysfunction and the development of complications after trauma.

PMID- 16959148
TI  - [Preparation and identification of polyclonal antiserum against heat shock
      protein 72].
AB  - OBJECTIVE: To express fusion protein of histamine (His) and human heat shock
      protein 72 (hHSP72) in Escherichia coli (E. coli), and to prepare hHSP72
      antiserum in rabbit. METHODS: hHSP72 gene was inserted into pPROEX-1. The
      recombinant vector was identified by restriction endonuclease digestion analysis
      and sequence. Fusion protein His-hHSP72 was expressed in E. coli under isopropyl
      beta-D-thiogalactoside (IPTG) induction. The rabbit antibody against His-hHSP72
      was prepared by using purified His-hHSP72 protein as immunogen, and the
      specificity and sensitivity of polyclonal antibody were identified by Western
      blot. RESULTS: The restriction endonuclease digestion analysis of recombinant
      plasmid and sequence demonstrated that the hHSP72 gene had been exactly inserted
      into pPROEX-1. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS
      PAGE) analysis showed that the relative molecular mass of the fusion protein was
      about 73 ku. Western blot result proved that the rabbit polyclonal antiserum
      could fuse with over 20 ng hHSP72 protein when diluted to 1:100,000. CONCLUSION:
      The polyclonal antibody against hHSP72 can be prepared in E. coli, it is a new
      reagent with high specificity and sensitivity for the research of hHSP72.

PMID- 16959147
TI  - [Effect of mesenteric lymph duct ligation on nitric oxide content and its
      expression in lung in rats with hemorrhagic shock].
AB  - OBJECTIVE: To observe the effect of mesenteric lymph duct ligation on nitric
      oxide (NO) and its expression in lung in rats with serious hemorrhagic shock at
      different periods, and explore the role of intestinal lymphatic pathway in acute
      lung injury (ALI). METHODS: Seventy-eight male Wistar rats were randomly divided
      into the sham operation group (n=6), shock group (n=42), and ligation group
      (n=30). The model of serious hemorrhagic shock was reproduced in shock group and
      ligation group. Mesenteric lymph was diverted by ligating mesenteric lymph duct
      in ligation group after resuscitation. All rats were executed and their lungs
      were harvested. NO and nitric oxide synthase (NOS) were determined in lung
      homogenate 90 minutes after shock, and 0, 1, 3, 6, 12 and 24 hours after
      resuscitation. The expression of inducible nitric oxide synthase (iNOS) mRNA was
      detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS:
      The content of NO, activity of NOS and expression of iNOS mRNA in lung tissue in
      shock group were increased 3 hours after transfusion and resuscitation, and they
      became higher 6-12 hours after resuscitation. The values were significantly
      higher than those in sham operation group, 90 minutes after shock and 0 hour
      after transfusion and resuscitation (P<0.05 or P<0.01). The values were only
      increased 3 hours and 6 hours after transfusion and resuscitation, and all the
      values on 6, 12 and 24 hours after resuscitation were significantly lower in the
      ligation group compared with those in shock group at the same time points (P<0.01
      or P<0.05). CONCLUSION: The results demonstrate that the ligation of mesenteric
      lymph duct could reduce the NO and expression of iNOS mRNA in the lung tissue,
      thus ameliorate ALI in rats with serious hemorrhagic shock. Mesenteric lymph
      might play an important role in the pathogenesis of ALI.

PMID- 16959149
TI  - [Investigation of relationship between prehospital care for traumatic shock and
      postoperative acute lung injury/acute respiratory distress syndrome].
AB  - OBJECTIVE: To investigate and analyze the correlation and clinical significance
      of prehospital treatment for traumatic shock and postoperative acute lung injury
      (ALI)/acute respiratory distress syndrome (ARDS). METHODS: Six hundred cases in
      the last 10 years were enrolled for double-blind randomized control study. They
      were divided into 3 groups. Group A consisted of 184 cases who had received
      combined treatment, group B consisted of 305 cases who had received fluid
      replacement only and group C consisted of 111 cases with no treatment. The
      incidence of systemic inflammatory response syndrome (SIRS), ALI and ARDS of each
      group were analyzed and compared. SIRS was graded at 1 (T0) after admission, 24
      (T1), 48 (T2), 96 (T3) and 144 hours (T4) after operation. RESULTS: In 524 cases
      diagnosis of SIRS was made among 600 patients (87.33%). Among them 73.37%
      (135/184 cases) were in group A, 91.48% (279/305 cases) belonged to group B and
      99.10% (110/111 cases) in group C. The scores of SIRS were notably lower in group
      A than B and C at each time point (all P<0.01), and they were lower in group B
      than those in group C (all P<0.01), they recovered at T3 after operation in group
      A while in group B patients recovered at 144 hours after operation. Eleven
      patients among 184 (5.98%) were diagnosed to have ALI including 1 case progressed
      to ARDS and 1 case to MODS and no one died, while in group B 32 cases in 305
      (10.49%) had ALI with 7 cases progressed to ARDS and 3 cases to MODS while 3
      deaths and in group C 23 among 111 (20.72%) had ALI, and 8 patients progressed to
      ARDS, 5 cases to MODS and 5 deaths. CONCLUSION: Prehospital treatment is closely
      related with postoperative ALI, and combined treatment is beneficial in reducing
      the incidence of postoperative ALI/ARDS.

PMID- 16959152
TI  - [Effect of ulinastatin on apoptosis in ileal mucosa of rats with hemorrhagic
      shock].
AB  - OBJECTIVE: To investigate the effect of ulinastatin on apoptosis in ileal mucosa
      of rats with hemorrhagic shock. METHODS: A prospective, controlled animal study
      was performed. The rat model of hemorrhagic shock was replicated according to
      method described by Chaudry. After 60 minutes period of bleeding, rats were
      resuscitated by transfusion of shed blood and normal saline. A part of the
      animals were additionally treated with ulinastatin. The expression of tumor
      necrosis factor-alpha (TNF-alpha), malondialdehyde (MDA) content in serum, and
      expression of Bax, Bcl-2, caspase 3 protein in ileal mucosa were determined at
      different time points after reperfusion. RESULTS: Compared with the normal saline
      group, the expression levels of TNF-alpha, MDA content in serum, Bax and caspase
      3 protein in ileal mucosa during hemorrhagic shock after resuscitation were
      significantly increased, while Bcl-2 protein was markedly decreased. After fluid
      resuscitation, obvious increase in MDA, Bcl-2 protein, significant decrease in
      the level of TNF-alpha, the expression of Bax and caspase 3 protein in ileal
      mucosa were observed in the ulinastatin group compared with normal saline group.
      CONCLUSION: Ulinastatin has protective effect on rats with hemorrhagic shock by
      suppressing the apoptosis in ileal mucosa.

PMID- 16959151
TI  - [Effect of fluid resuscitation on adhesion molecule and hemodynamics in patients
      with severe sepsis].
AB  - OBJECTIVE: To explore the effects of fluid resuscitation on adhesion molecule and
      hemodynamics in patients with severe sepsis. METHODS: Thirty-eight patients with
      severe sepsis were randomly divided into 2 groups: rapid fluid resuscitation
      group and general treatment group. Before and after fluid resuscitation, heart
      rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), lactic
      acid content, plasma P-selection and intercellular adhesion molecule-1 (ICAM-1)
      contents were determined. RESULTS: There were no statistically significant
      differences in sex, age, resuscitation time and acute physiology and chronic
      health evaluation II (APACHE II) score between the two groups. Compared with
      general treatment group, more liquid volume but less aramine dosage were used
      (both P<0.05), MAP and CVP were increased after fluid resuscitation in rapid
      fluid resuscitation group (all P<0.05). The expression of P-selection, HR,
      contents of ICAM-1 and lactic acid were decreased (all P<0.05), and all of those
      were better than those of before fluid resuscitation. CONCLUSION: Early rapid
      fluid resuscitation can improve hemodynamics and decrease the expression of
      adhesion molecule to retard the development of sepsis.

PMID- 16959154
TI  - [Effects of gavage with lactococcus lactis recombinant heme oxygenase-1 gene on
      inflammation of intestine and bacterial translocation in rats with hemorrhagic
      shock].
AB  - OBJECTIVE: To evaluate the effects of gavage with lactococcus lactis (L. Lactis)
      recombinant heme oxygenase-1 (HO-1) gene on alleviation of intestinal
      inflammation and protection of the intestinal mucosa in rats with hemorrhagic
      shock. METHODS: A model of rats with hemorrhagic shock was reproduced in 30
      healthy SD male rats. The rats were randomly divided into the L. Lactis
      recombinant HO-1 gene group (HO group, n=10), L. Lactis group (LL group, n=10)
      and phosphate buffer group (PBS group, n=10). These agents were respectively
      gavaged 24 hours before the experiment. Rats were re-anesthetized 1 hour after
      fluid resuscitation. The mortality, myeloperoxidase (MPO) activity, bacterial
      translocation, the pathologic changes, the contents of HO-1, tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-10 (IL-10) in the intestine were
      determined and compared. RESULTS: Compared with LL group and PBS group, the
      mortality, Chiu's grade and the bacterial translocation rate of HO group were
      significantly decreased (all P<0.05) but the content of HO-1 and the level of IL
      10 in HO group were markedly increased (both P<0.05). Compared with HO group and
      LL group, the MPO activity of PBS group was obviously increased (P<0.05).
      CONCLUSION: The recombinant L. Lactis has the effect to deliver HO-1, which has
      protective effect on the intestinal mucosa in lessening the inflammation of the
      intestine and the incidence of bacterial translocation.

PMID- 16959156
TI  - [Effect of hydroxyethyl starch on vascular reactivity of rat during hemorrhagic
      shock].
AB  - OBJECTIVE: To study the effect of hydroxyethyl starch (HES) on vascular
      reactivity of rat during hemorrhagic shock and its mechanism. METHODS: Forty SD
      rats were randomly divided into 5 groups: normal control group, shock group,
      sodium chloride (SC) group, HES 130/0.4 group and HES 200/0.5 group with 8 rats
      in each group. Rats were hemorrhaged and maintained mean arterial pressure (MAP)
      at 40 mm Hg (1 mm Hg=0.133 kPa) for 30 minutes, then rats were infused with
      fluids to restore and maintain MAP at 70 mm Hg for 60 minutes. The infusion
      volumes of each fluid to maintain MAP were recorded. The responses of MAP to
      norepinephrine (NE) were measured before shock, at 30, 60 and 90 minutes during
      hemorrhagic shock. Concentrations of nitric oxide (NO) and nitric oxide synthase
      (NOS) of plasma were measured at 90 minutes during hemorrhagic shock. RESULTS:
      The infusion volumes of each fluid to maintain MAP were significantly different
      (all P<0.01). HES 200/0.5 group<HES 130/0.4 group<SC group. In HES 130/0.4 group
      and HES 200/0.5 group at 90 minutes during hemorrhagic shock, the responses of
      MAP to NE were improved significantly compared with those of SC group (both
      P<0.05), plasma contents of NO and NOS were reduced markedly compared with those
      of SC group (P<0.05 or P<0.01). CONCLUSION: HES can improve vascular reactivity
      during hemorrhagic shock by inhibiting plasma contents of NO and NOS.

PMID- 16959157
TI  - [Expression of Toll-like receptor 2/4 mRNA in myocardium in mice with hemorrhagic
      shock].
AB  - OBJECTIVE: To investigate the effect of hemorrhagic shock without resuscitation
      on expression of Toll-like receptor (TLR) in myocardium of rats and its
      significance. METHODS: Forty-five C57BL/6 mice were randomly divided into 3
      groups: hemorrhagic group, sham operation group and lipopolysaccharide (LPS)
      group, with 15 mice in each group. The hemorrhagic shock mouse model was
      reproduced by heart puncture. Expression levels of TLR2 mRNA and TLR4 mRNA were
      determined by reverse transcription-polymerase chain reaction (RT-PCR). Left
      ventricular end-systolic pressure (LVESP) was determined and adopted as an index
      of left ventricle contractile function. RESULTS: (1)Both hemorrhagic shock and
      LPS challenge led to a reduction in arterial blood pressure in mice when compared
      with sham operation group. Both hemorrhagic shock and LPS challenge could result
      in left ventricle contractile dysfunction when compared with sham operation
      group. (2)Expression levels for TLR2 and TLR4 genes were upregulated in
      myocardium to various extents after hemorrhagic shock and LPS challenge, while in
      contrast the changes were absent in sham operation group. CONCLUSION: (1)The up
      regulation of TLR2 and TLR4 genes is closely related with hemorrhagic shock and
      LPS-induced left ventricle contractile dysfunction, and there may exist a
      difference in signal transduction pathway between the two pathological
      conditions. (2)The host ability of innate immune response may be reinforced by
      the up-regulation of TLR2 and TLR4, whereas overexpression of them may also
      impair the function of tissues or organs.

PMID- 16959160
TI  - [Alteration in serum contents of P-selection and nitric oxide synthase in
      patients serum during traumatic shock and its clinical implication].

PMID- 16959158
TI  - [Effect of methylene blue on traumatic shock in rabbits].
AB  - OBJECTIVE: To observe the effect of methylene blue (MB) on the changes in plasma
      nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6)
      and visceral pathologic changes in rabbits with traumatic shock. METHODS:
      Eighteen rabbits were randomly assigned into 3 groups (n=6): sham operation
      group, traumatic shock with normal saline (NS) resuscitation group (NS group),
      and traumatic shock with MB resuscitation group (MB group). In NS group and MB
      group, hemodynamics was monitored, and plasma contents of NO, TNF-alpha and IL-6
      were determined before shock, after shock, after resuscitation, and 0.5, 2 and 4
      hours after resuscitation. In sham operation control group, hemodynamics
      monitoring and plasma contents of NO, TNF-alpha and IL-6 were also determined.
      Tissue samples of the liver and intestine were obtained after experiments for
      microscopic examination. RESULTS: Compared with NS group, hemodynamics was stable
      in MB group. The levels of plasma NO in rabbits after traumatic shock were much
      higher than those of before shock. In NS group, the levels of plasma NO were
      progressively increased after resuscitation, reaching peak level at 0.5 hour
      after resuscitation, then decreased thereafter but still remaining higher than
      those of before shock. But in MB group, the levels of plasma NO after
      resuscitation were obviously decreased. In sham operation group, the levels of
      plasma NO showed no significant changes during the whole course. The levels of
      plasma TNF-alpha and IL-6 in rabbits after traumatic shock were much higher than
      those of before shock. But after intravenous administration of MB, the levels of
      plasma TNF-alpha and IL-6 after resuscitation showed no significant difference
      compared with the baseline levels. In sham operation group, the levels of plasma
      TNF-alpha and IL-6 showed no significant changes during the entire course. In NS
      group, the organs showed prominent pathologic changes. But in MB group, less
      pathologic changes in the organs were milder, and in sham operation group, there
      was no obvious pathologic changes in the organs. CONCLUSION: NO, TNF-alpha and IL
      6 play important roles in the pathologic process of traumatic shock and the
      administration of MB after resuscitation can decrease the levels of plasma NO,
      TNF-alpha and IL-6, improve hemodynamics in traumatic shock, and protect the
      important organs.

PMID- 16959161
TI  - [Treatment with combined transfusion of frozen platelets and freshly frozen
      plasma in acute massive hemorrhage].

PMID- 16959169
TI  - Computerised cognitive behaviour therapy for depression and anxiety update: a
      systematic review and economic evaluation.
AB  - OBJECTIVES: To evaluate computerised cognitive behaviour therapy (CCBT) for the
      treatment of anxiety, depression, phobias, panic and obsessive-compulsive
      behaviour (OCD). The software packages to be considered include Beating the Blues
      (BtB), Overcoming Depression: a five areas approach, FearFighter (FF), Cope and
      BT Steps. Other packages or programmes incorporating CCBT were also considered.
      DATA SOURCES: Electronic databases from 1966 to March 2004. Evidence submitted by
      sponsors for CCBT products. REVIEW METHODS: A systematic review was a review of
      the literature and the evidence submitted by sponsors for each of the products. A
      series of cost-effectiveness models was developed and run by the project team for
      the five CCBT products across the three mental health conditions. RESULTS: Twenty
      studies were identified in the clinical effectiveness review. The analysis of
      these results showed some evidence that CCBT is as effective as therapist-led
      cognitive behaviour therapy (TCBT) for the treatment of depression/anxiety and
      phobia/panic and is more effective than treatment as usual (TAU) in the treatment
      of depression/anxiety. CCBT also appears to reduce therapist time compared with
      TCBT. When reviewing cost-effectiveness studies, only one published economic
      evaluation of CCBT was found. This was an economic evaluation of the depression
      software BtB alongside a randomised controlled trial (RCT), which found that BtB
      was cost-effective against TAU in terms of cost per quality-adjusted life-year
      (QALY) (less than 2000 pounds), however it contained weaknesses that were then
      addressed in the cost-effectiveness model developed for the study. The results of
      the model for the depression software packages in terms of incremental cost per
      QALY compared with TAU and the chance of being cost-effective at 30,000 pounds
      per QALY were for BtB 1801 pounds and 86.8%, for Cope 7139 pounds and 62.6% and
      for Overcoming Depression 5391 pounds and 54.4%. The strength of the BtB software
      being that it has been evaluated in the context of an RCT with a control group.
      The subgroup analysis found no differences across the severity groupings. For
      phobia/panic software, the model showed an incremental cost per QALY of FF over
      relaxation was 2380 pounds. Its position compared with TCBT is less clear. When
      modelling OCD packages, using the practice-level licence cost meant that BT Steps
      was dominated by TCBT, which had significantly better outcomes and was cheaper.
      However, the cheaper PCT licence resulted in the incremental cost-effectiveness
      of BT Steps over relaxation being 15,581 pounds and TCBT over BT Steps being
      22,484 pounds. CONCLUSIONS: The study findings are subject to substantial
      uncertainties around the organisational level for purchasing these products and
      the likely throughput. This is in addition to concerns with the quality of
      evidence on response to therapy, longer term outcomes and quality of life. The
      position of CCBT within a stepped care programme needs to be identified, as well
      as its relationship to other efforts to increase access to CBT and psychological
      therapies. Research is needed to compare CCBT with other therapies that reduce
      therapist time, in particular bibliotherapy and to explore the use of CCBT via
      the Internet. Independent research is needed, particularly RCTs, that examine
      areas such as patient preference and therapist involvement within primary care.

PMID- 16959171
TI  - Psychological therapies including dialectical behaviour therapy for borderline
      personality disorder: a systematic review and preliminary economic evaluation.
AB  - OBJECTIVES: To summarise the available evidence on the clinical effectiveness and
      cost-effectiveness of psychological therapies including dialectical behaviour
      therapy (DBT) for borderline personality disorder (BPD). DATA SOURCES: Electronic
      databases were searched up to March 2005. REVIEW METHODS: Relevant studies were
      assessed using standard checklists and data were abstracted by two reviewers
      using standardised forms. Separate economic evaluations were undertaken for six
      selected randomised controlled trials (RCTs). Cost-effectiveness was assessed in
      terms of cost per parasuicide event avoided in all six trials and cost per
      quality-adjusted life-year (QALY) in four of them. All results are at 2003-4
      prices and for 12 months follow-up. RESULTS: Nine RCTs and one non-RCT of
      moderate to poor quality were identified in the clinical effectiveness review.
      They provided some evidence that DBT is more effective than treatment as usual
      (TAU) for the treatment of chronically parasuicidal and drug-dependent borderline
      women; that DBT-orientated therapy is more effective than client-centred therapy
      (CCT) for the treatment of BPD; and that DBT is as effective as comprehensive
      validation therapy plus 12-Step for the treatment of opioid-dependent borderline
      women. There was also some evidence that partial hospitalisation is more
      effective than TAU in the treatment of BPD, good evidence that manual-assisted
      cognitive behavioural therapy (MACT) is no more effective than TAU in the
      treatment of BPD and some evidence that interpersonal group therapy is no more
      effective than individual mentalisation-based partial hospitalisation (MBT) for
      the treatment of BPD. However, these results should be interpreted with caution
      as not all studies were primarily targeted to borderline symptoms and there were
      considerable differences between the studies. The assessment of cost
      effectiveness found a mix of results in the four trials of DBT, along with the
      high levels of uncertainty and the limitations in the analyses. The findings do
      not support the cost-effectiveness of DBT though they suggest it has the
      potential to be cost-effective. The results for MBT are promising, though again
      surrounded by a high degree of uncertainty and for MACT, the analysis suggests
      that the intervention is unlikely to be cost-effective. CONCLUSIONS: The overall
      efficacy of psychological therapies is promising; however, at this stage the
      evidence is inconclusive. The cost-effectiveness of the intervention in six RCTs
      examined, however, does not support the cost-effectiveness of DBT although
      potential is suggested. There is a need for considerable research in this area.
      This research should involve appropriately powered head-to-head RCTs of
      psychological therapies; a survey of current practice and the use of the full
      range of services by people with BPD to inform future economic analyses; full
      resource-use data collected in the context of pragmatic clinical trials;
      psychometric assessment of the validity of the EQ-5D or other generic and
      condition-specific preference-based measures in BPD, and the development of a
      more formal cost-effectiveness model using the above data.

PMID- 16959170
TI  - Cost-effectiveness of using prognostic information to select women with breast
      cancer for adjuvant systemic therapy.
AB  - OBJECTIVES: To investigate the cost-effectiveness of using prognostic information
      to identify patients with breast cancer who should receive adjuvant therapy. DATA
      SOURCES: Electronic databases from 1980 through to February 2002. A survey of
      clinical practice in UK cancer centres and units. Large retrospective dataset
      containing data on prognostic factors, treatments and outcomes for women with
      early breast cancer treated in Oxford. REVIEW METHODS: Between six and nine
      databases were searched by an information expert. Evidence-based methods were
      used to review and select those studies and the quality of each included paper
      was assessed using standard assessment tools reported in the literature or
      piloted and developed for this study. A survey of clinical practice in UK cancer
      centres and units was carried out to ensure that conclusions drawn from the
      report could be implemented. These data, along with the information gathered in
      the systematic reviews, informed the methodological approach adopted for the
      health economic modelling. An illustrative framework was developed for
      incorporating patient-level prediction within a health economic decision model.
      This framework was applied to a large retrospective dataset containing data on
      prognostic factors, treatments and outcomes for women with early breast cancer
      treated in Oxford. The data were used to estimate directly a parametric
      regression-based risk equation, from which a prognostic index was developed, and
      prognosis-specific estimates of the baseline breast cancer hazard could be
      observed. Published estimates of treatment effects, health service treatment
      costs and utilities were used to construct a decision analytic framework around
      this risk equation, thus enabling simulation of the effectiveness and cost
      effectiveness of adjuvant therapy for all possible combinations of prognostic
      factors included in the model. RESULTS: The lack of good-quality systematic
      reviews and well-conducted studies of prognostic factors in breast cancer is a
      striking finding. There are no registers of studies of prognostic factors or of
      reviews of prognostic studies. Many of the reviews used weak methods, primary
      studies are similar with poor methodology and reporting of results. In addition,
      there is much variation in patient populations, assay methods, analysis of
      results, definitions used and reporting of results. Most studies appear to be
      retrospective and some use inappropriate methods likely to inflate outcomes such
      as optimising cut points and failing to test the results in an independent
      population. Very few reviews used meta-analysis to conduct a pooled analysis and
      to provide an estimate of the average size of any association. Instead, most
      reviews relied on vote counting. Although many prognostic models for breast
      cancer have been published, remarkably few have been re-examined by independent
      groups in independent settings. The few validation studies have been carried out
      on ill-defined samples, sometimes of smaller size and short follow-up, and
      sometimes using different patient outcomes when validating a model. The evidence
      from the validation studies shows support for the prognostic value of the
      Nottingham Prognostic Index (NPI). No new prognostic factors have been shown to
      add substantially to those identified in the 1980s. Improvement of this index
      depends on finding factors that are as important as, but independent of, lymph
      node, stage and pathological grade. The NPI remains a useful clinical tool,
      although additional factors may enhance its use. We accepted that hormone
      receptor status (ER) for hormonal therapy such as tamoxifen and prediction of
      response to trastuzumab by HER2 did not require systematic review, as the
      mechanism of action of these drugs requires intact receptors. There was no clear
      evidence that other factors were useful predictors of response and survival. The
      survey confirmed pathological nodal status, tumour grade, tumour size and ER
      status as the most clinically important factors for consideration when selecting
      women with early breast cancer for adjuvant systemic therapy in the UK. The
      protocols revealed that although UK cancer centres appear to be using the same
      prognostic and predictive factors when selecting women to receive adjuvant
      therapy, much variation in clinical practice exists. Some centres use protocols
      based upon the NPI whereas others do not use a single index score. Within NPI and
      non-NPI users, between-centre variability exists in guidelines for women for whom
      the benefits are uncertain. Consensus amongst units appears to be greatest when
      selecting women for adjuvant hormone therapy with the decision based primarily
      upon ER or progesterone receptor status rather than combinations of a number of
      factors. Guidelines as to who should receive adjuvant chemotherapy, however, were
      found to be much less uniform. Searches of the literature revealed only five
      published papers that had previously examined the cost-effectiveness of using
      prognostic information for clinical decision-making. These studies were of
      varying quality and highlight the fact that economic evaluation in this area
      appears still to be in its infancy. By combining methodologies used in
      determining prognosis with those used in health economic evaluation, it was
      possible to illustrate an approach for simulating the effectiveness (survival and
      quality-adjusted survival) and the cost-effectiveness associated with the
      decision to treat individual women or groups of women with different prognostic
      characteristics. The model showed that effectiveness and cost-effectiveness of
      adjuvant systemic therapy have the potential to vary substantially depending upon
      prognosis. For some women therapy may prove very effective and cost-effective,
      whereas for others it may actually prove detrimental (i.e. the reductions in
      health-related quality of life outweigh any survival benefit). CONCLUSIONS:
      Outputs from the framework constructed using the methods described here have the
      potential to be useful for clinicians, attempting to determine whether net
      benefits can be obtained from administering adjuvant therapy for any presenting
      woman; and also for policy makers, who must be able to determine the total costs
      and outcomes associated with different prognosis based treatment protocols as
      compared with more conventional treat all or treat none policies. A risk table
      format enabling clinicians to look up a patient's prognostic factors to determine
      the likely benefits (survival and quality-adjusted survival) from administering
      therapy may be helpful. For policy makers, it was demonstrated that the model's
      output could be used to evaluate the cost-effectiveness of different treatment
      protocols based upon prognostic information. The framework should also be
      valuable in evaluating the likely impact and cost-effectiveness of new potential
      prognostic factors and adjuvant therapies.

PMID- 16959172
TI  - The current role of urethrotomy in anterior urethral stricture disease.

PMID- 16959173
TI  - Functional obstructed voiding in the neurologically normal patient.
AB  - Voiding dysfunction is common and often is the result of urethral obstruction to
      urine flow. Obstruction can be due to failure of the sphincteric mechanism to
      sufficiently relax. Such functional obstructions may have smooth and/or striated
      muscle components. Identifying and characterizing functional bladder outlet
      obstruction enables the physician to effectively treat these symptomatic
      patients.

PMID- 16959174
TI  - The impact of detrusor overactivity on the management of stress urinary
      incontinence in women.
AB  - The presence of overactive bladder symptoms, urodynamic detrusor overactivity,
      and urge incontinence can complicate the diagnosis and management of stress
      urinary incontinence in women. The exact pathophysiology of mixed incontinence is
      not well characterized; in some patients, the stress and urge etiology may be
      pathologically linked. The role of urodynamics in evaluating patients with mixed
      incontinence remains controversial. Conservative therapies, such as bladder
      training, pelvic floor exercise, biofeedback, and electrical stimulation, offer
      moderate success in women with mixed incontinence. Surgery (colposuspension,
      bladder neck pubovaginal slings, and midurethral slings) offers excellent
      subjective and objective cure rates in patients with mixed incontinence.
      Preoperative detrusor overactivity is cured consistently 50%of the time with
      colposuspension and slings. Overall, the presence of preoperative detrusor
      overactivity does not appear to significantly worsen the outcome of conservative
      and surgical treatments for stress urinary incontinence in women.

PMID- 16959175
TI  - Bladder outlet obstruction in women: iatrogenic, anatomic, and neurogenic.
AB  - This paper outlines the presentation, evaluation, and management of bladder
      outlet obstruction (BOO) in women as it relates to iatrogenic, anatomic, and
      neurogenic causes. Attention is given to the different diagnostic criteria used
      by various authors in their case series and studies. The lack of standardization
      with regard to the diagnosis of BOO in women emphasizes the fact that BOO is
      often a clinical diagnosis that is made by taking into account the history,
      physical examination, imaging of the lower urinary tract, and urodynamic pressure
      flow parameters. Individual obstructive conditions including urethral stricture,
      postsurgical obstruction, primary bladder neck obstruction, pelvic organ
      prolapse, and neurogenic causes are addressed briefly.

PMID- 16959176
TI  - Evaluation and management of refractory overactive bladder.
AB  - The refractory overactive bladder patient is a complex new entity for the
      urologic community. We present the most current review of this difficult subject
      matter with an emphasis on evaluation and new treatment options such as sacral
      neuromodulation and botulinum toxin injection. It is hoped that in this new era
      of medical innovation, extirpation and reconstruction of the bladder will become
      historic in nature and refractory therapy can be transitioned to the office and
      outpatient operation rooms.

PMID- 16959177
TI  - A urogynecologist's view ofthe pelvic floor effects of vaginal delivery/cesarean
      section for the urologist.
AB  - Pregnancy and parturition have been implicated in the development of pelvic floor
      dysfunction. These disorders include urinary incontinence, fecal incontinence,
      pelvic organ prolapse, and other pelvic and sexual dysfunctions. The urologist
      caring for women with urinary dysfunction needs to be familiar with the causes of
      pelvic floor dysfunction and their implications. Defects of the pelvic floor have
      clearly resulted from the traumatic effect of vaginal delivery. The likely
      mechanisms of injuries during vaginal delivery involve stretching and compression
      of the pudendal nerve and peripheral branches, as well as an additional tearing
      of muscles and connective tissue. Optimal management of labor and optimal
      techniques of repair of unavoidable sphincteric lacerations, ante- and postpartum
      pelvic floor muscle conditioning, and timely and proper indications for cesarean
      delivery will minimize the effect of incidental traumatic delivery.

PMID- 16959178
TI  - Methods and results of urethrolysis.
AB  - Although occurring with somewhat less frequency now than historically reported,
      outlet obstruction after incontinence surgery continues to be a source of
      postoperative patient dissatisfaction and therapeutic dilemma. Several techniques
      have been described that fall under the rubric of urethrolysis, including sling
      incision, sling lysis with explantation, and formal vaginal or retropubic
      urethrolysis (incision and disruption of bladder neck and urethral fibrosis).
      Surgical approaches have included vaginal, retropubic, or combined techniques
      with or without the use of adjunctive steps such as graft interposition. However,
      evidence emanating from reports of these varied techniques has been incomplete
      due to variability in outcomes presentation, lack of longevity of follow-up, or
      problematic study design. Nonetheless, the bulk of clinical evidence supports the
      efficacy of urethrolysis as an intervention for outlet obstruction after stress
      incontinence surgery. However, persistent irritative bladder symptoms remain
      bothersome for some women and, in addition, the recurrence of stress incontinence
      also may complicate the technique of urethrolysis. Management of these potential
      adverse outcomes also has been inconsistent, with some authorities routinely
      performing repeat incontinence surgery at the time of urethrolysis and others
      preferring to assess continence status after convalescence from urethrolysis. The
      differences among the types of urethrolysis and the results of each type are
      reviewed in this article in light of evolving definitions of outlet obstruction,
      diagnosis, and definition in women.

PMID- 16959179
TI  - Urodynamic assessment of sphincteric function in the incontinent female: which
      test, and does it matter anyway?
AB  - The overall prevalence of urinary incontinence among women surveyed in the United
      States is approximately 37%. The lifetime risk of undergoing urinary incontinence
      surgery for women in the United States is estimated to be 11.1%. Conservative
      therapy can be instituted without performing extensive evaluation such as
      urodynamics, voiding cystourethrograms, ultrasonography, or video studies.
      Further evaluation is recommended when conservative measures have failed or if
      invasive, potentially morbid surgical therapies are being considered. This paper
      reviews the available methods for evaluating the urinary sphincter in the
      incontinent female.

PMID- 16959180
TI  - Emerging periurethral bulking agents for female stress urinary incontinence: is
      new necessarily better?
AB  - Bulking therapy for stress urinary incontinence in women continues to evolve from
      the standpoint of material science. Several new materials have recently been
      subjected to clinical trials with the aim of assessing efficacy and safety of
      these agents for possible device registration. These new additions run the gamut
      of biologic to synthetic materials, including re-engineered carbon-coated
      zirconium beads, ethylene vinyl copolymer, calcium hydroxylapatite, silicone, and
      hyaluronic acid. Trial design and results reporting for bulking agents has also
      evolved, with the addition of quality-of-life and patient approbation assessments
      now being included with outcomes for incontinence reduction and adverse events
      recording. The new agents and recent studies are reviewed within a context of the
      prior evidence that has supported the use of the bulking strategy for management
      of symptomatic stress incontinence. Several recent trials have also compared
      bulking agents with surgical interventions from effectiveness, approbation, and
      cost vantage points so as to better determine the reasonability of bulking agent
      use in an era of minimally invasive incontinence surgery.

PMID- 16959182
TI  - Management of the neurogenic bladder in the female patient.
AB  - Management of the female patient with neurogenic bladder requires special
      considerations that are not seen with many male neurogenic bladder patients.
      Because of the unique challenges that certain women present, a disproportionate
      number of women end up with an indwelling catheter or continuously leak urine
      into a diaper. Other options for bladder management include intermittent
      catheterization and reconstruction, which, when used appropriately, can lead to
      significant improvements in urinary continence, quality of life, and patient
      independence. This article reviews the various options available today as well as
      several potential therapies that may be available in the future.

PMID- 16959181
TI  - Urinary and Serologic Markers forInterstitial Cystitis: An Update.
AB  - This update reviews the published literature from the past 2 years pertaining to
      urinary and serum markers for interstitial cystitis (IC). Literature on markers
      described before 2004 also is included when needed to provide background
      information for the current literature. The markers that have been the focus of
      the most research in the recent literature are antiproliferative factor,
      epidermal growth factor, heparin-binding epidermal growth factor-like growth
      factor, glycosaminoglycans, and bladder nitric oxide. These markers are discussed
      in consideration of their three different possible roles: 1) as diagnostic
      markers of IC; 2) distinguishing relevant subsets of IC patients; and 3)
      measuring disease activity and objectively following treatment response.

PMID- 16959183
TI  - Formulation modifications of PD 0313052, a direct Factor Xa Inhibitor, alter
      pharmacokinetics and pharma-codynamics following subcutaneous administration to
      rabbits.
AB  - PURPOSE: PD 0313052 is a potent, direct factor Xa (FXa) inhibitor (Ki = 0.33 nM)
      and its antithrombotic effect has been previously demonstrated in several animal
      models, via intravenous (IV) administration. In the present study, we evaluated
      four different subcutaneous (SC) formulations to test the feasibility of
      developing PD 0313052 as a subcutaneous agent. METHODS: PD 0313052 was formulated
      in saline, methylcellulose (MC, 0.5% methylcellulose solution containing 1% Tween
      80), sesame oil, and F127 (25% aqueous solution). Each formulation was injected
      subcutaneously into rabbits and the relative plasma exposure and the duration of
      action of PD 0313052 were assessed. Plasma concentration, FXa activity, and
      coagulation parameters were used to monitor the pharmacokinetic (PK) and
      pharmacodynamic (PD) profiles of PD 0313052. RESULTS: Regardless of formulation,
      there was a significant (p < 0.05) correlation between PD 0313052 plasma
      concentration and FXa activity (R2 = 0.90), prothrombin time (PT) (R2 = 0.86),
      and Heptest (R2 = 0.93). The saline and MC formulations had similar effects on
      FXa activity, coagulation parameters, and Heptest, peaking at 30 to 120 minutes
      after administration and decreasing rapidly thereafter. In contrast, formulations
      of F127 and sesame oil yielded lower maximal effects on PD markers but produced
      sustained PD effects over time. CONCLUSION: The data indicate that PD 0313052 is
      bioavailable after SC administration to rabbits and that there is a strong
      correlation between the PD parameters and plasma concentrations of PD 0313052.
      Modifications in the formulation of PD 0313052 produce marked differences in the
      PK and PD profiles of this agent after SC administration to rabbits. These
      results suggest that SC formulations can be optimized to improve the PK and PD
      profiles of PD 0313052, and that PD 0313052 is a viable candidate for development
      as a SC antithrombotic agent.

PMID- 16959184
TI  - Pharmaceutical care services in hospitals of Kuwait.
AB  - PURPOSE: To describe the current pharmacy practice in the general public
      hospitals based on self-reported practice by pharmacists, explore the awareness
      of the pharmacists of pharmaceutical care concept, identify their willingness to
      implement pharmaceutical care practice, and identify the barriers that may limit
      its implementation. METHODS: Eighty hospital pharmacists working in four general
      public hospitals were approached to be included in the study. Data were colleted
      via face-to-face structured interview of the respondents using a pre-tested
      questionnaire. RESULTS: The response rate was 76.3%. Thirty five (57.4%) of the
      respondents had frequently performed interventions on prescriptions through
      interaction with physicians. Thirty two (52.5%) had frequently provided patient
      counselling. The knowledge of the respondents about the counseling points for
      salbutamol inhaler was assessed using a total score of 10, 35 (57.4%) scored = 5.
      The frequent provision of counseling was non-significantly least common among the
      > 40 years group compared to youngest age group (OR: 0.7, 0.3-1.9), male gender
      (0.6, 0.2-1.4) and those with a practice experience of > 20 years (0.4, 0.1-1.2).
      Forty six (75.4%) of the respondents reported that they were aware of
      pharmaceutical care concept. Thirty five (76.1%) and 39.1% of those who reported
      awareness of pharmaceutical care concept indicated that its main focus is the
      patient and the appropriate objectives of the concept, respectively. The
      awareness about the patient as the main focus of pharmaceutical care was non
      significantly least among the respondents aged 41-60 years (OR: 0.6, 0.2-2.4) and
      those with a practice experience of 21-40 years (0.3, 0.1-1.0). The main barriers
      perceived by the participants were lack of time (78%) and lack of staff (71.2%).
      CONCLUSION: The current practice of hospital pharmacists in Kuwait needs further
      improvement in relation to interaction with physicians and patient counselling.
      The lack of uniformity in the responses regarding the focus and objectives of
      pharmaceutical care indicates a lack of appropriate understanding in this matter.
      All respondents have shown high willingness towards the implementation of
      pharmaceutical care services in their practice.

PMID- 16959185
TI  - Development of a sensitive and specific liquid chromatography/mass spectrometry
      method for the quantification of cucurbitacin I (JSI-124) in rat plasma.
AB  - PURPOSE: To develop a liquid chromatography/mass spectrometry (LC-MS) method for
      the quantitative analysis of cucurbitacin I (JSI-124), an anti-cancer inhibitor
      of the janus kinase 2/signal transducer and activator of transcription 3
      (JAK2/STAT3) signaling pathway, in rat plasma samples. METHODS: Standard samples
      of cucurbitacin I were prepared from a stock solution (1 mg/mL) in methanol.
      Internal standard (I.S.) was 4-hydroxybenzophenone. Extraction of cucurbitacin I
      and I.S. from rat plasma was performed using acetonitrile/dichloromethane. LC-MS
      analyses were performed using a Waters Micromass ZQ 4000 spectrometer, and
      chromatographic separation was achieved using a Waters XTerraMSC18 3.5 microm
      (2.1 x 50 mm) column as the stationary phase. The mobile phase consisting of a
      mixture of acetonitrile: water containing 1% formic acid with initial ratio of
      20:80, employing a linear gradient to a final ratio of 40:60 v/v over 13 minutes,
      was delivered at a constant flow rate of 0.2 mL/min. The mass spectrometer was
      operated in negative ionization mode and analytes were quantified with single ion
      recording (SIR) at m/z 559 for cucurbitacin I and m/z 196.8 for I.S. RESULTS:
      Calibration curves with r2 > 0.999 were constructed over the concentration range
      of 5-10000 ng/mL for the solution of cucurbitacin I in methanol and 10-1000 ng/mL
      for rat plasma samples. The extraction recoveries were 86 and 98% for 50 ng/mL
      and 1000 ng/mL plasma concentration of cucurbitacin I, respectively. The intra-
      and inter-day coefficients of variation were less than 15%, and mean intraday
      errors were less than 10% at plasma concentration extending from 10-1000 ng/mL.
      CONCLUSION: The developed assay is sensitive, specific, reproducible and reliable
      for quantitative analysis of cucurbitacin I. Application in a pharmacokinetic
      assessment was proven in the rats given the drug.

PMID- 16959186
TI  - Production and characterization of monoclonal antibodies against shope fibroma
      virus superoxide dismutase and glutathione-s-transferase.
AB  - PURPOSE: The superoxide dismutase (SOD) like proteins encoded by Leporipoxviruses
      play a role in regulating the redox status of infected cells. The biological
      function of these proteins is unclear. Why poxviruses encode these proteins are
      still unknown. Exploiting standard hybridoma techniques, we developed a
      monoclonal antibody (MAb) against shope fibroma virus superoxide dismutase
      (sfvSOD) to be used in diagnostics and as tools to understand the role of SOD
      like proteins in pathogenesis. METHODS: Hybridoma cell fusion technology was used
      for production of MAbs. Balb/c mice were immunized with sfvSOD-GST fusion
      protein. Hybridoma clones were screened using indirect enzyme linked
      immunosorbent assay (ELISA). Specificity and reactivity of the MAbs were
      determined by Western blot analysis (WBA) and indirect ELISA. Protein G affinity
      chromatography was used for the purification of MAbs. RESULTS: Two stable
      hybridoma clones producing MAbs against the two domains of the fusion protein
      were obtained. The anti-GST (glutathione-s-transferase) and anti-sfvSOD MAbs were
      found to react specifically with GST and sfvSOD proteins respectively, in
      addition to the sfvSOD-GST fusion protein. Isotypes of these MAbs were identified
      as IgG2b heavy chain and k light chain. CONCLUSION: The anti-sfvSOD MAb (P115.SOD
      MAb) has been successfully used in studying the enzymatic and biochemical
      properties of a SOD homolog encoded by sfv. We also developed a strong anti-GST
      MAb which was also cloned and characterized P115.GST MAb. The anti-GST MAb might
      be useful in analyzing GST fusion proteins and in immunoaffinity chromatography
      purification of GST fusion proteins.

PMID- 16959187
TI  - In vitro - in vivo correlation: from theory to applications.
AB  - A key goal in pharmaceutical development of dosage forms is a good understanding
      of the in vitro and in vivo performance of the dosage forms. One of the
      challenges of biopharmaceutics research is correlating in vitro drug release
      information of various drug formulations to the in vivo drug profiles (IVIVC).
      Thus the need for a tool to reliably correlate in vitro and in vivo drug release
      data has exceedingly increased. Such a tool shortens the drug development period,
      economizes the resources and leads to improved product quality. Increased
      activity in developing IVIVCs indicates the value of IVIVCs to the pharmaceutical
      industry. IVIVC can be used in the development of new pharmaceuticals to reduce
      the number of human studies during the formulation development as the main
      objective of an IVIVC is to serve as a surrogate for in vivo bioavailability and
      to support biowaivers. It supports and/or validates the use of dissolution
      methods and specification settings. This is because the IVIVC includes in vivo
      relevance to in vitro dissolution specifications. It can also assist in quality
      control for certain scale-up and post-approval changes (SUPAC). With the
      proliferation of modified-release products, it becomes necessary to examine the
      concept of IVIVC in greater depth. Investigations of IVIVC are increasingly
      becoming an integral part of extended release drug development. There must be
      some in vitro means of assuring that each batch of the same product will perform
      identically in vivo. This review article represents the FDA guidance,
      development, evaluation, and validation of an IVIVC to grant biowaivers, and to
      set dissolution specifications for oral dosage forms, biopharmaceutics
      classification systems (BCS), BCS biowaivers, application of BCS in IVIVC
      development and concept of mapping. The importance of dissolution media and
      methodology and pharmacokinetic studies in the context of IVIVC has been
      highlighted. The review also covers the literature examples of IVIVCs regarding
      internal and external validation, compendial dissolution assessment, formulation
      dependency of IVIVCs, and IVIVCs of pure enantiomers versus racemate drugs. The
      same principles of IVIVC used for oral extended release products may be applied
      for non-oral products such as parenteral depot formulations and novel drug
      delivery systems as well.

PMID- 16959188
TI  - Epinephrine infiltration on nasal field causes significant hemodynamic changes:
      hypotension episode monitored by impedance-cardiography under general anesthesia.
AB  - PURPOSE: Local infiltration of epinephrine-containing local anesthetics is widely
      used in clinics particularly in the procedure of surgeries on vascularity field
      to provide good analgesia and hemostasis. A prospective randomized double blind
      control study was designed to observe hemodynamic changes caused by local
      infiltration of epinephrine- containing lidocaine solution on nasal field under
      general anesthesia. METHODS: 90 adult patients undergoing elective functional
      endoscopic sinus surgery under general anesthesia were randomly allocated into
      three groups and received 1% lidocaine 4 mL with different dose of epinephrine
      (group I 20 microg; group II 40 microg; and group III 0 microg) respectively.
      Mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), systemic
      vascular resistance index (SVRI), and acceleration index (ACI) were recorded
      through impedance-cardiography at every 45 seconds in 6 minutes after the
      beginning of local infiltration. RESULTS: Compared with the intra-group baseline,
      statistically significant hemodynamic changes particularly decrease in MAP with
      increase in HR at 1.5 minutes time point (P < 0.01), and decrease in SVRI and
      increase in CI, ACI at and from 1.5 minutes time point (P > 0.05) were observed
      in group I and group II, but not in group III. CONCLUSION: Local infiltration of
      epinephrine-containing lidocaine solution on nasal field causes significant
      decrease in MAP and SVRI, and increase in HR, CI and ACI.

PMID- 16959189
TI  - Evaluation of the anti-proliferative effect the extracts of Allamanda blanchetti
      and A. schottii on the growth of leukemic and endothelial cells.
AB  - PURPOSE: To investigate the anti-proliferative effect of A. blanchetti and A.
      schottii extracts. METHODS: The anti-proliferative effect of A. blanchetti and A.
      schottii ethanolic extracts on K562 leukemic cells as well as on BMEC and HUVEC
      were evaluated. Phytochemical analysis to identify the possible active components
      was carried out. RESULTS: The root extract of A. schottii was the most active of
      them. At 80 microg/mL, the root extracts showed a cytostatic effect on K562,
      whereas at 400 microg/mL, there was a strong cytotoxic effect. Similar cytostatic
      and cytotoxic effects were seen in the endothelial cells, but at lower doses. The
      effect of A. schottii root extract on endothelial cells was seen at
      concentrations ten times lower (8 microg/mL) than the effect of the A. blanchetti
      root extract (80 microg/mL). Phytochemical investigation of different fractions
      and parts of the plant led to the isolation of several known compounds, some of
      which are described for the first time in the genus Allamanda, and with previous
      evidence of anticancer and antitumoral properties. CONCLUSIONS: Our results
      suggest that both plants studied exhibit cytostatic and cytotoxic activity, but
      the most active compounds are located in the roots.

PMID- 16959190
TI  - Predicting Caco-2 permeability using support vector machine and chemistry
      development kit.
AB  - PURPOSE: To predict Caco-2 permeability is a valuable target for pharmaceutical
      research. Most of the Caco-2 prediction models are based on commercial or special
      software which limited their practical value. This study represents the
      relationship between Caco-2 permeability and molecular descriptors totally based
      on open source software. METHODS: The Caco-2 prediction model was constructed
      based on descriptors generated by open source software Chemistry Development Kit
      (CDK) and a support vector machine (SVM) method. Number of H-bond donors and
      three molecular surface area descriptors constructed the prediction model.
      RESULTS: The correlation coefficients (r) of the experimental and predicted Caco
      2 apparent permeability for the training set and the test set were 0.88 and 0.85,
      respectively. CONCLUSION: The results suggest that the SVM method is effective
      for predicting Caco-2 permeability. Membrane permeability of compounds is
      determined by number of H-bond donors and molecular surface area properties.

PMID- 16959191
TI  - Atorvastatin has distinct effects on endothelial markers in different mouse
      models of atherosclerosis.
AB  - PURPOSE: Atherosclerosis is a progressive process that initially involves
      endothelial dysfunction. We investigated the effects of atorvastatin on both
      lipid parameters, and VCAM-1 and ICAM-1 expression in apoE-deficient or wild type
      C57BL/6J mice. METHODS: The C57BL/6J mice were fed with either chow or an
      atherogenic diet for 12 weeks. Male apoE-deficient mice were fed with the chow
      diet for 12 weeks. In 3 atorvastatin treated groups mice were fed the same diet
      as described above except atorvastatin was added to the diet at the dosage of 10
      mg/kg per day for the last 8 weeks before euthanasia. RESULTS: Biochemical
      analysis showed that atorvastatin significantly decreased total cholesterol
      levels and VLDL in C57BL/6J mice fed with atherogenic diet but increased serum
      lipid levels in apoE-deficient mice. Stereological analysis of the
      immunohistochemical staining revealed that atorvastatin reduced endothelial
      expression of ICAM-1 and VCAM-1 only in C57BL/6J mice on chow diet. CONCLUSION:
      We have demonstrated that endothelial expression of both VCAM-1 and ICAM-1 does
      not correlate with cholesterol levels in these mice. Moreover, we showed that 8
      week administration of atorvastatin decrease endothelial expression of VCAM-1 and
      ICAM-1 in C57BL/6J wild type mice beyond its lipid lowering effect but not in
      C57BL/6J wild type mice fed by atherogenic diet or in apoE-deficient mice.

PMID- 16959192
TI  - Determination of free concentration of Paclitaxel in liposome formulation.
AB  - PURPOSE: An important step in the development of liposome-based formulations is
      estimating the free drug concentration in the aqueous solution surrounding
      liposomes. This research presents a new method for determination of free
      concentrations, based on membrane-protected solid-phase microextraction (SPME).
      METHODS: For effective direct extraction of low molecular weight compounds from
      complex liquid samples, a hollow membrane was used to form a concentric sheath
      around a coated SPME fiber. The membrane blocked the access of large particles,
      like liposomes, to the coating surface, while target analytes with low molecular
      weight diffused through the membrane and reached the extraction phase.
      Quantification was conveniently performed by reversed-phase liquid chromatography
      coupled to electrospray ionization mass spectrometry. RESULTS: The
      carbowax/templated resin SPME fiber was determined to be the most suitable for
      these assays, providing enough sensitivity when an extraction time of one hour
      was used. The free concentration of paclitaxel was found to be 0.36 microg/mL,
      significantly below the solubility limit of paclitaxel in water. CONCLUSION: The
      method was successfully applied for determining free paclitaxel in liposome
      formulations based on dioleyl-trimethyl-ammonium-propane, with good linearity
      over the range of concentrations of interest. The method was faster and more
      practical than equilibrium dialysis, as the SPME approach provided
      preconcentration and convenient delivery to the analytical system.

PMID- 16959193
TI  - A common profile for polymer-based controlled releases and its logical
      interpretation to general release process.
AB  - PURPOSE: The release of drug from a polymeric matrix is complicated. It often
      involves drug diffusion, interface movement and various interactions. It also
      shows a dependence on the length of polymer rod. With Lc as the 'critical
      length', three different phases can be distinguished from the kinetic process.
      Prior to reaching Lc, the interface movement plays a key role on determining the
      release. Otherwise, the drug diffusion can dominate the release process. Near Lc,
      however, both factors are involved. The rate of interface movement is closely
      associated with the time and position in the polymer rod. Taking these characters
      into account, a common model is presented in this article to be tentatively used
      to interpret the release process. These results provide preliminarily an insight
      into the understanding of controlled release process.

PMID- 16959194
TI  - Exercise hemodynamic and neurohormone responses as sensitive biomarkers for
      diltiazem in rats.
AB  - PURPOSE: To investigate the potential of exercise hemodyanamic and neurohormone
      variables as sensitive biomarkers for pre-clinical evaluation of diltiazem (DTZ).
      METHODS: Sprague Dawley (SD) rats were randomly divided into 3 groups (n = 6 - 8
      each), and each group received DTZ 10 mg/kg twice daily for 5 doses or saline
      followed by a treadmill exercise protocol for 7 min with speed set at 7 m/min at
      3 % grade. The 3rd group received saline but no exercise. RESULTS: Exercise
      increased SBP from 108 +/- 2 to 131 +/- 3 mmHg, and HR from 437 +/- 6 to 503 +/-
      6 bpm, and plasma epinephrine concentrations from 2.0 +/- 0.6 to 5.8 +/- 1.7
      ng/mL in control rats (p < 0.05 for all variables), but had no significant effect
      on DBP (81 +/- 5 vs 87 +/- 6 mmHg) and plasma norepinephrine concentrations (1.5
      +/- 0.2 vs 3.9 +/- 0.4 ng/mL). The hemodynamic responses to exercise were
      significantly attenuated by DTZ (p < 0.05), but the effect on neurohormone
      response was minimal (p > 0.05). CONCLUSION: Exercise hemodynamic and
      neurohormone responses are sensitive biomarkers which could be used for safety
      and efficacy evaluation of DTZ and perhaps also other calcium antagonists in pre
      clinical animal models.

PMID- 16959195
TI  - In silico prediction of drug solubility in water-ethanol mixtures using Jouyban
      Acree model.
AB  - PURPOSE: A predictive method was proposed to predict solubility of drugs in water
      ethanol mixtures at various temperatures based on the Jouyban-Acree model. The
      model requires the experimental solubility data of the drug in mono-solvent
      systems. METHODS: The accuracy of the proposed prediction method was evaluated
      using collected experimental solubility data from the literature. The proposed
      method is: log Xm,T = fc log Xc,T + fw log Xw,T + fcfw[724.21/T + 485.17(fc-fw)/T
      + 194.41(fc-fw)2/T] Where Xm,T, Xc,T and Xw,T are the solute solubility at
      temperature (T) in mixed solvent and neat cosolvent and water, respectively, fc
      and fw denote the solute free fraction of cosolvent (ethanol) and water. The
      average absolute error (AAE) of the experimental and the predicted solubilities
      was computed as an accuracy criterion and compared with that of a well
      established log-linear model. RESULTS: The AAE (+/-SD) of the Jouyban-Acree and
      log-linear models were 0.19 (+/-0.13) and 0.48 (+/-0.28), respectively. The mean
      difference of AAEs was statistically significant (p < 0.0005) revealing that the
      Jouyban-Acree model was provided more accurate predictions. Although the log
      linear model was used to predict solubility at a fixed temperature (25 or 23
      degrees C), the results also showed that the model could be employed to predict
      the solubility in solvent mixtures at various temperatures. CONCLUSION: More
      accurate predictions were provided using the Jouyban-Acree model in comparison
      with a previously established log-linear model of Yalkowsky. The prediction
      methods were successfully extended to predict the solubility in water-ethanol
      mixtures at various temperatures.

PMID- 16959196
TI  - Driver behaviour, dilemma zone and safety effects at urban signalized
      intersections in Greece.
AB  - Driving behaviour at signalized intersections is one of the main factors
      contributing to the safety level of such entities. This behaviour, with respect
      to yellow signal obedience or violation, is examined at a signalized intersection
      in Thessaloniki, Greece. The data, collected for the study purposes, include
      vehicles' speeds and distance from stop line when exposed to yellow light, gender
      and age group of drivers as well as reaction of Platoon leaders and first
      followers. Drivers were grouped into three categories, namely conservative,
      normal and aggressive, according to their behaviour at the intersection, the
      existence of a dilemma or option zone and their initial approaching speed. A
      binary choice model was also developed relating the probability of stopping at
      the STOP line or crossing it as a function of approach speed, distance from
      intersection, gender, age group and the existence or not of a dilemma zone. The
      findings of this research indicate that a large percentage of drivers facing the
      yellow signal are caught in a dilemma zone due to high approaching speeds and
      exercise an aggressive behaviour. The distribution of drivers into the three
      categories changes with differing assumptions pertaining to the factors affecting
      the calculation of safe stopping distance and critical crossing distance as well
      as speed thresholds for determining a priori aggressive behaviour. The research
      concludes that aggressive drivers represent a high percentage of all drivers and
      measures towards improving driving behaviour and/or reducing vehicles' speeds are
      required.

PMID- 16959197
TI  - The influence of perceptual speed regulation on speed perception, choice, and
      control: tunnel wall characteristics and influences.
AB  - The present work sought to determine if the type of visual pattern and presence
      of texture applied to transportation tunnel walls differentially affected driving
      performance. Choice of speed and speed control were measured with 32 participants
      who drove through a simulated transportation tunnel environment. Participants
      experienced three visual patterns consisting of vertical segments that decreased,
      increased, and remained a constant width throughout the length of the tunnel.
      Participants also drove a baseline control condition in which no visual pattern
      was present. Each of these conditions was presented either with or without a
      homogenous texture. When compared to the baseline condition, results indicated
      drivers gradually decreased speed when exposed to the decreasing width visual
      pattern and increased speed with the increasing width visual pattern. The
      presence of texture served to attenuate overall driving speed. Results suggest
      drivers' perception of speed and their subsequent response to such perceptions
      were modified by the visual pattern and texture expressed on the tunnel wall. The
      evident speed control opportunities afforded to the traffic engineer are
      discussed.

PMID- 16959199
TI  - Distant malignant recurrence after laparoscopically assisted radical vaginal
      trachelectomy in patients with early uterine cervical cancer.

PMID- 16959200
TI  - Value of laparoscopic assistance for vaginal delivery.

PMID- 16959203
TI  - Serum and urine inhibin A but not free activin A are endocrine biomarkers of
      severe pre-eclampsia.
AB  - OBJECTIVE: Elevation of total serum inhibin A and activin A has been interpreted
      as evidence of placental dysfunction in women who develop pre-eclampsia. We
      sought to evaluate serum and urine levels of inhibin A and free activin A in
      normal and hypertensive pregnancies. STUDY DESIGN: Inhibin A and free activin A
      were measured by immunoassay in simultaneously collected serum and urine samples
      from 75 women: (1) severe pre-eclampsia (n = 30); (2) mild pre-eclampsia (n =
      11); (3) chronic hypertension (n = 9); (4) pregnant control women (n = 16); and
      (5) nonpregnant control women (n = 9). Urine levels were normalized to milligrams
      urine creatinine, and fractional excretions were calculated. RESULTS: Serum and
      urine inhibin A were increased and fractional excretion was decreased in
      pregnancy. Serum, urine, and fractional excretion of inhibin A were increased in
      severe pre-eclampsia, compared with other gravidas. The only difference observed
      in free activin A was a decrease in serum free activin A in chronic hypertension,
      compared with severe pre-eclampsia and pregnant control women. Urine inhibin A
      showed the greatest discrimination between severe pre-eclampsia and pregnant
      control women: a cut-off of 45 pg/mg urine creatinine had 96.8% sensitivity,
      87.5% specificity, and 93.6% accuracy. Women with urine inhibin A greater than 90
      pg/mg urine creatinine had a 17-fold relative risk (95% confidence interval 9.7
      459.5) of a clinically indicated delivery due to pre-eclampsia. CONCLUSION: Serum
      and urine levels of inhibin A are altered in severe pre-eclampsia. Urine inhibin
      A may have application in the diagnosis and management of pre-eclampsia. Those
      with chronic hypertension have lower serum but not urine free activin A levels,
      compared with severe pre-eclampsia and mild pre-eclampsia.

PMID- 16959206
TI  - Universal herpes screening in pregnancy: not recommended and potentially harmful
      to patients.

PMID- 16959207
TI  - Financial relationships between research and pharmaceutical/biotech companies:
      disclosure is imperative.

PMID- 16959209
TI  - Placental mesenchymal stem cells.

PMID- 16959211
TI  - The tripartite model for assessing symptoms of anxiety and depression:
      psychometrics of the Dutch version of the mood and anxiety symptoms
      questionnaire.
AB  - AIM: The tripartite model conceptualizes symptoms of depression and anxiety in
      three groups: low positive affect and anhedonia, which is specific to depression,
      somatic arousal, which is unique to anxiety, and nonspecific general distress.
      The Mood and Anxiety Symptoms Questionnaire (MASQ) was developed to measure these
      symptom domains. This study reports on the psychometric properties of the Dutch
      translation of the MASQ. METHOD: The questionnaire was completed by a population
      based sample and by patients with anxiety and/or mood disorders. Scores of these
      respondent groups were compared to assess the discriminant validity of the MASQ
      and evaluate the appropriateness of the tripartite model. RESULTS: The
      psychometric properties of the translated MASQ were highly satisfactory. In
      accordance with the model, we found the MASQ to comprise three main scales, which
      discriminate well between subgroups of patients with mood and anxiety disorders.
      DISCUSSION: Overall, like the English version the Dutch translation of the
      instrument appears to be a reliable and valid measure of symptoms of depression
      and anxiety, conceptualized as comprising three groups of symptoms. The Dutch
      MASQ is better able to distinguish unique aspects of mood and anxiety disorders
      than other self-report instruments.

PMID- 16959210
TI  - Cysteine 98 in CYP3A4 contributes to conformational integrity required for P450
      interaction with CYP reductase.
AB  - Previously human cytochrome P450 3A4 was efficiently and specifically
      photolabeled by the photoaffinity ligand lapachenole. One of the modification
      sites was identified as cysteine 98 in the B-C loop region of the protein [B.
      Wen, C.E. Doneanu, C.A. Gartner, A.G. Roberts, W.M. Atkins, S.D. Nelson,
      Biochemistry 44 (2005) 1833-1845]. Loss of CO binding capacity and subsequent
      decrease of catalytic activity were observed in the labeled CYP3A4, which
      suggested that aromatic substitution on residue 98 triggered a critical
      conformational change and subsequent loss of enzyme activity. To test this
      hypothesis, C98A, C98S, C98F, and C98W mutants were generated by site-directed
      mutagenesis and expressed functionally as oligohistidine-tagged proteins. Unlike
      the mono-adduction observed in the wild-type protein, simultaneous multiple
      adductions occurred when C98F and C98W were photolabeled under the same
      conditions as the wild-type enzyme, indicating a substantial conformational
      change in these two mutants compared with the wild-type protein. Kinetic analysis
      revealed that the C98W mutant had a drastic 16-fold decrease in catalytic
      efficiency (V(max)/K(m)) for 1'-OH midazolam formation, and about an 8-fold
      decrease in catalytic efficiency (V(max)/K(m)) for 4-OH midazolam formation,
      while the C98A and C98S mutants retained the same enzyme activity as the wild
      type enzyme. Photolabeling of C98A and C98S with lapachenole resulted in
      monoadduction of only Cys-468, in contrast to the labeling of Cys-98 in wild-type
      CYP3A4, demonstrating the marked selectivity of this photoaffinity ligand for
      cysteine residues. The slight increases in the midazolam binding constants (K(s))
      in these mutants suggested negligible perturbation of the heme environment.
      Further activity studies using different P450:reductase ratios suggested that the
      affinity of P450 to reductase was significantly decreased in the C98W mutant, but
      not in the C98A and C98S mutants. In addition, the C98W mutant exhibited a 41%
      decrease in the maximum electron flow rate between P450 and reductase as measured
      by reduced nicotinamide adenine dinucleotide phosphate consumption at a
      saturating reductase concentration. In conclusion, our data strongly suggest that
      cysteine 98 in the B-C loop region significantly contributes to conformational
      integrity and catalytic activity of CYP3A4, and that this residue or residues
      nearby might be involved in an interaction with P450 reductase.

PMID- 16959212
TI  - Synergistic protective effect of ischemic preconditioning and allopurinol on
      ischemia/reperfusion injury in rat liver.
AB  - This study examined the effects of ischemic preconditioning (IPC), allopurinol
      (Allo) or a combination of both on the extent of mitochondrial injury caused by
      hepatic ischemia/reperfusion (I/R). I/R increased the serum aminotransferase
      activity and the level of mitochondrial lipid peroxidation, whereas it decreased
      the mitochondrial glutathione level. Either IPC or Allo alone attenuated these
      changes with Allo+IPC having a synergistic effect. Allo increased the serum
      nitrite and nitrate level after brief ischemia. The significant peroxide
      production observed after 10 min of reperfusion after sustained ischemia was
      markedly attenuated by Allo+IPC. The mitochondria isolated after I/R were
      swollen, which was reduced by Allo+IPC. At the end of ischemia, the hepatic ATP
      level was lower and there was significant xanthine accumulation, which was
      attenuated by Allo+IPC. These results suggest that IPC and Allo act
      synergistically to protect cells against mitochondrial injury and preserve the
      hepatic energy metabolism during hepatic I/R.

PMID- 16959213
TI  - The epigenetic silencing of LIMS2 in gastric cancer and its inhibitory effect on
      cell migration.
AB  - Recent finding has shown that LIMS2 (also known as PINCH2) functions as a natural
      regulator of the LIMS1-ILK-parvin complex formation and is associated with cell
      spreading and migration via integrins at focal adhesions. Here, we report for the
      first time the epigenetic silencing of LIMS2 in gastric tumors. Downregulation of
      LIMS2 was detected in 91% (10 of 11) of gastric cancer cell lines by real-time
      quantitative RT-PCR and 80% (8 of 10) of the LIMS2-downregulated cell lines were
      associated with CpG island hypermethylation at a 5'-upstream region of LIMS2.
      Furthermore, LIMS2 was restored in its non-expressing cell lines after treatment
      with 5-Aza-dC and/or trichostatin A. Loss of expression of LIMS2 was also
      detected in 53% (51 of 96) of primary gastric tumors. This decrease in expression
      level significantly correlated with an increase of the CpG island
      hypermethylation. In addition, the methylation status in any normal-appearing
      gastric tissues was gradually increased in an age-dependent manner, suggesting
      that the positive methylation in normal-appearing gastric mucosa can be due to
      'field cancerization effect' as an early event in gastric carcinogenesis.
      Moreover, the transient transfection of LIMS2-siRNA significantly stimulated cell
      migration in gastric cancer cells but had no effects on cell growth. These
      results suggest that the frequent inactivation of LIMS2 by epigenetic alteration
      in gastric cancer may be important in tumor progression events, such as invasion
      and metastasis. Thus, LIMS2 may be useful as a molecular biomarker and a
      therapeutic target by increasing its expression and activity in gastric cancer.

PMID- 16959214
TI  - Malignant hematopoietic cells induce an increased expression of VEGFR-1 and VEGFR
      3 on bone marrow endothelial cells via AKT and mTOR signalling pathways.
AB  - Angiogenesis plays a significant role in a variety of malignant hematologic
      diseases, and it is recognized that it has prognostic value. However, the
      cellular mechanisms by which malignant hematologic cells induce angiogenesis are
      not well understood. In order to investigate the role of cells from B-cell
      chronic lymphocytic leukemia (B-CLL) and multiple myeloma (MM) in angiogenesis on
      human bone marrow endothelial cells (HBMEC), we analyzed the impact of factors
      secreted by B-CLL cells and by MM cells on HBMEC capillary tube formation on
      matrigel. It was found that, in addition to the secretion of angiogenic factors
      VEGF and b-FGF by B-CLL and MM cells, MM cells (but not B-CLL cells) induced a
      dramatic increase in expression of VEGFR-1 and VEGFR-3 on human bone marrow
      endothelial cells (HBMEC). It would seem that this increase in VEGFR-3 occurred
      via the ERK and mTOR pathways, since their respective inhibitors U0126, LY294002
      or rapamycin were responsible for a decrease of VEGFR-3. In response to MM cells
      increased VEGF receptors on HBMEC, endothelial cell migration was enhanced in a
      wound artificially produced in a semi-confluent HBMEC culture, a phenomenon which
      was also down-regulated by the same inhibitors that reversed the increase in VEGF
      receptors. The present study suggests that, in addition to the classic angiogenic
      pathway, another mechanism related to an increased expression of VEGFRs on HBMEC
      might exist in malignant hematopoietic angiogenesis.

PMID- 16959215
TI  - Reduction of Nomega-hydroxy-L-arginine to L-arginine by pig liver microsomes,
      mitochondria, and human liver microsomes.
AB  - Nomega-Hydroxy-L-arginine, the intermediate in nitric oxide formation from L
      arginine catalyzed by NO synthase, can be released into the extracellular space.
      It has been suggested that it can circulate and exert paracrine effects. Since it
      cannot only be used as substrate by NO synthases, but can also be oxidized by
      cytochrome P450 and other hemoproteins in a superoxide-dependent manner, it has
      been proposed that it can serve as NO donor. In the present study, the in vitro
      reduction of Nomega-hydroxy-L-arginine was examined. Pig and human liver
      microsomes as well as pig liver mitochondria were capable of reducing Nomega
      hydroxy-L-arginine to L-arginine in an oxygen-insensitive enzymatic reaction.
      These results demonstrate that this metabolic pathway has to be considered when
      suggesting Nomega-hydroxy-L-arginine as NO-precursor. The reconstituted liver
      microsomal system of a pig liver CYP2D enzyme, the benzamidoxime reductase, was
      unable to replace microsomes to produce L-arginine from Nomega-hydroxy-L
      arginine.

PMID- 16959216
TI  - Involvement of DDAH/ADMA/NOS pathway in nicotine-induced endothelial dysfunction.
AB  - Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS)
      inhibitor, is a key contributor for endothelial dysfunction. Decrease in activity
      of dimethylarginine dimethylaminohydrolase (DDAH), a major hydrolase of ADMA,
      causes accumulation of ADMA under cardiovascular abnormalities. The study was to
      determine whether nicotine-induced endothelial dysfunction is related to
      modulating DDAH/ADMA/NOS pathway. Four-week oral nicotine treatment (5 mg/kg/day)
      significantly increased the plasma level of ADMA and decreased aortic DDAH
      expression as well as impaired endothelial function in Sprague-Dawley rats.
      Similarly, the medium levels of both ADMA and lactate dehydrogenase were markedly
      elevated in umbilical vein endothelial cells (HUVECs) treated with nicotine (10
      microM) for 48 h. Nicotine-induced endothelial damages were markedly attenuated
      by L-arginine or overexpression of DDAH-II. Nicotine greatly downregulated both
      mRNA and protein levels of DDAH-II, and decreased DDAH activity in HUVECs. HUVECs
      express alpha7 nicotinic acetylcholine receptor (alpha7 nAChR), whose antagonists
      could block these effects of nicotine mentioned above. Intracellular Ca2+
      chelator did not affect nicotine-induced decrease in DDAH-II mRNA level. In
      conclusion, nicotine modulates DDAH/ADMA/NOS pathway of endothelial cell via
      activation of alpha7 nAChR, which may be involved in endothelial dysfunction
      associated to smoking.

PMID- 16959217
TI  - Electrical behavior and pore accumulation in a multicellular model for
      conventional and supra-electroporation.
AB  - Extremely large but very short (20 kV/cm, 300 ns) electric field pulses were
      reported recently to non-thermally destroy melanoma tumors. The stated mechanism
      for field penetration into cells is pulse characteristic times faster than charge
      redistribution (displacement currents). Here we use a multicellular model with
      irregularly shaped, closely spaced cells to show that instead overwhelming pore
      creation (supra-electroporation) is dominant, with field penetration due to pores
      (ionic conduction currents) during most of the pulse. Moreover, the model's
      maximum membrane potential (about 1.2 V) is consistent with recent experimental
      observations on isolated cells. We also use the model to show that conventional
      electroporation resulting from 100 microsecond, 1 kV/cm pulses yields a spatially
      heterogeneous electroporation distribution. In contrast, the melanoma-destroying
      pulses cause nearly homogeneous electroporation of cells and their nuclear
      membranes. Electropores can persist for times much longer than the pulses, and
      are likely to be an important mechanism contributing to cell death.

PMID- 16959218
TI  - Different roles of histone H3 lysine 4 methylation in chromatin maintenance.
AB  - Histone H3 methyltransferases are involved in the epigenetic control of
      transcription and heterochromatin maintenance. In Saccharomyces cerevisiae,
      deletion of a histone H3 methyltransferase SET1 leads to the induction of a
      subset of stress responsive genes in a Rad53 dependent manner. This type of
      induction was observed only in the absence of SET1 and not in the absence of
      other histone methyltransferases, SET2 or DOT1. We show that the increased
      expression of the stress responsive genes results from a lack of histone H3
      lysine (K) 4 methylation. The loss of mono-methylation on H3 K4 is necessary to
      increase the expression of the stress responsive genes, while the loss of di- or
      tri-methylation induced by deletion of either RRM domain of Set1 or the upstream
      effector molecules hardly affected their expression. These results suggest that
      mono- and multiple methylation of H3 K4 have different roles. The mono
      methylation of H3 K4 might be required for the global integrity of chromatin
      structure, which is normally monitored by the Rad53 dependent chromatin
      surveillance system.

PMID- 16959219
TI  - Prostanoids in nociception and pain.
AB  - Prostaglandins are lipid mediators produced by cyclooxygenases from arachidonic
      acid, which serve pivotal functions in inflammation and pain. Inhibition of their
      production is the major analgesic mechanism of action of non-steroidal anti
      inflammatory drugs (NSAIDs)-but also the source of most of their unwanted
      effects. While the development of selective inhibitors of inducible
      cyclooxygenase (COX)-2 (so called coxibs) has greatly reduced gastrointestinal
      side effects, the recent disappointment about a potential cardiovascular toxicity
      of COX-2-selective inhibitors has boosted interest in alternative targets. The
      discovery of several prostaglandin synthases and of distinct prostaglandin
      receptors has unraveled an unforeseen diversity within the prostanoid synthetic
      pathway. Behavioral and electrophysiological work in particular with genetically
      engineered mice meanwhile provides new clues to the role of different
      prostaglandins, prostaglandin synthases and prostaglandin receptors in pain
      pathways.

PMID- 16959220
TI  - Therapeutic and preventive properties of quercetin in experimental arthritis
      correlate with decreased macrophage inflammatory mediators.
AB  - Pentahydroxyflavone dihydrate, quercetin (QU) is one of common flavonols
      biosynthesized by plants and has been suggested to modulate inflammatory
      responses in various models. In the present study, we investigated in vivo
      effects of oral or intra-cutaneous QU in chronic rat adjuvant-induced arthritis
      (AA). Growth delay and arthritic scores were evaluated daily after AA induction
      in Lewis rats. Oral administration of QU (5 x 160 mg/kg) to arthritic rats
      resulted in a clear decrease of clinical signs compared to untreated controls.
      Intra-cutaneous injections of lower doses (5 x 60 mg/kg) of QU gave similar anti
      arthritic effects, while 5 x 30 mg/kg concentrations were inefficient in this
      respect. Finally, injection of relatively low QU doses (5 x 30 mg/kg) prior to AA
      induction significantly reduced arthritis signs. As QU was suggested to inhibit
      macrophage-derived cytokines and nitric oxide (NO), we then analyzed macrophage
      response ex vivo. Anti-arthritic effects of QU correlated with significant
      decrease of inflammatory mediators produced by peritoneal macrophages, ex vivo
      and in vitro. These data indicate that QU is a potential anti-inflammatory
      therapeutic and preventive agent targeting the inflammatory response of
      macrophages.

PMID- 16959221
TI  - The HSP90 and DNA topoisomerase VI inhibitor radicicol also inhibits human type
      II DNA topoisomerase.
AB  - Radicicol derivatives are currently investigated as promising antitumoral drugs
      because they inhibit the activity of the molecular chaperone heat shock protein
      (HSP90), causing the destabilization and eventual degradation of HSP90 client
      proteins that are often associated with tumor cells. These drugs interact with
      the ATP-binding site of HSP90 which is characterized by a structural element
      known as the Bergerat fold, also present in type II DNA topoisomerases (Topo II).
      We have previously shown that radicicol inhibits archaeal DNA topoisomerase VI,
      the prototype of Topo II of the B family (present in archaea, some bacteria and
      all the plants sequenced so far). We show here that radicicol also inhibits the
      human Topo II, a member of the A family (comprising the eukaryotic Topo II,
      bacterial gyrase, Topo IV and viral Topo II), which is a major target for
      antitumoral drugs. In addition, radicicol prevents in vitro induction of DNA
      cleavage by human Topo II in the presence of the antitumoral drug etoposide. The
      finding that radicicol can inhibit at least two different antitumoral drug
      targets in human, and interferes with drugs currently used in cancer treatment,
      could have implications in cancer therapy.

PMID- 16959222
TI  - Curcumin regulates signal transducer and activator of transcription (STAT)
      expression in K562 cells.
AB  - Signal transducers and activators of transcription (STATs) play important roles
      in numerous cellular events as for example differentiation, inflammation or
      immune response. Furthermore, constitutive STAT activation can be observed in a
      high number of tumors. In our hands, curcumin treatment induced a decrease of
      nuclear STAT3, -5a and -5b, without affecting neither STAT1, nor the
      phosphorylation state of STAT1, -3 or -5 in the K562 cell line. Most
      interestingly, the decrease of nuclear STAT5a and -5b after curcumin treatment
      was accompanied by an increase of truncated STAT5 isoforms, indicating that
      curcumin is able to induce the cleavage of STAT5 into its dominant negative
      variants lacking the STAT5 C-terminal region. Interferon (IFN)-beta and -gamma
      treatment induced IFN-stimulated responsive element (ISRE) transcriptional
      activity, which was efficiently inhibited by curcumin pre-treatment. In parallel,
      IFN-gamma treatment induced an increase of the amount of nuclear STAT1 and -3, as
      well as their phosphorylated isoforms. Again, curcumin pre-treatment inhibited
      these increases. Finally, curcumin treatment inhibited Jak2 mRNA expression as
      well as cyclin D1 and v-src gene expression in K562 chronic leukaemia cells.

PMID- 16959223
TI  - p63 and p73, members of the p53 gene family, transactivate PKCdelta.
AB  - The p53 family comprises three genes that encode for p53, p63 and p73. These
      genes have a significant degree of sequence homology, especially in the central
      sequence-specific DNA-binding domain. The high homology among the three DNA
      binding domains indicates that these transcription factors have identical
      residues interacting with DNA, and thus potentially can recognize the same
      transcriptional targets. In this study, we demonstrate that PKCdelta is induced
      by p63 and p73 in Saos2 cells. The putative human PKCdelta promoter harbours
      three p53-like binding sites (RE I, RE II, RE III). In order to confirm the
      transactivation of PKCdelta by p53 family members, we performed transcription
      assays using the entire or selected regions of the promoter upstream of a
      luciferase reporter gene. The results obtained demonstrated that, at least in
      vitro, the p53 family members tested (TAp63alpha, TAp73alpha, DeltaNp63alpha, but
      not DeltaNp73alpha) were able to drive transcription from the PKCdelta promoter.

PMID- 16959224
TI  - Memantine reduces striatal cell death with decreasing calpain level in 3
      nitropropionic model of Huntington's disease.
AB  - Huntington's disease has an increase in the activated calpain, which is enhanced
      by the NMDA receptor activation. We investigated the neuroprotective effect of
      memantine in 3-nitropropionic acid (3NP)-induced striatal degeneration model.
      Either memantine (20 mg/kg/day) or PBS was intraperitoneally administered for
      five days with 3NP continuous infusion. In the memantine-treated group, the
      striatal lesion volume, the number of TUNEL+ cells, and Fluoro-Jade C+
      degenerating neurons were all decreased. Memantine increased Bcl-xl and decreased
      Bax level. Memantine also exerted an inhibitory effect on the micro-calpain level
      and decreased the huntingtin proteolytic fragments. Those rats treated with
      memantine showed less degree of weight loss at 5 days. Subsequently, memantine
      was found to have neuroprotective effects and save striatal cells with decreasing
      calpain levels in the 3NP model of Huntington's disease.

PMID- 16959225
TI  - Adult mesenchymal stem cells rescue dorsal root ganglia neurons from dying.
AB  - Mesenchymal stem cells (MSCs) can differentiate into multiple cellular lineages
      including neuronal cells. However, the positive effect of MSCs on repairing the
      nervous tissue has not yet been completely understood. In order to investigate
      the influence of MSCs on a neuronal population, we co-cultured MSCs, obtained by
      flushing the bone diaphisis from adult Sprague-Dawley rats, with DRG post-mitotic
      sensory neurons obtained from rat embryos at day E15. Co-cultures were maintained
      for 2 months. The adult rat MSCs, simply harvested in a pure culture of DRG
      neurons, allow the long-lasting survival and maturation of neurons otherwise
      committed to die. Neurons, when co-cultured with rat fibroblasts, do not survive
      as long as with MSCs and do not mature to the same degree. The rescue effect of
      MSCs on neurons is achieved only by cellular direct contact. These results
      provide a valid explanation for the functional improvement reported in some in
      vivo experiments.

PMID- 16959226
TI  - Brain activation when hearing one's own and others' names.
AB  - Using functional magnetic resonance imaging, brain activation patterns were
      examined in response to hearing one's own first name in contrast to hearing the
      names of others. There are several regions in the left hemisphere that show
      greater activation to one's own name, including middle frontal cortex, middle and
      superior temporal cortex, and cuneus. These findings provide evidence that
      hearing one's own name has unique brain functioning activation specific to one's
      own name in relation to the names of others.

PMID- 16959227
TI  - Tadalafil, a long-acting type 5 phosphodiesterase isoenzyme inhibitor, improves
      neurological functional recovery in a rat model of embolic stroke.
AB  - Sildenafil, a type 5 phosphodiesterase isoenzyme (PDE5) inhibitor with a short
      half-life, increases brain cyclic guanosine monophosphate (cGMP) levels and
      improves neurological functional recovery when administered after stroke. In the
      present study, we investigated the effects of tadalafil (Cialis), a long acting
      PDE5 inhibitor, on brain cGMP levels, neurogenesis, angiogenesis, and
      neurological function during stroke recovery in a rat model of embolic stroke.
      Male Wistar rats (n=28) were subjected to embolic middle cerebral artery (MCA)
      occlusion. Tadalafil was orally administered every 48 h at a dose of 2 mg/kg or
      10 mg/kg for 6 consecutive days starting 24 h after stroke onset. Control animals
      received the equivalent volume of saline at the same time points. For mitotic
      labeling, bromodeoxyuridine (BrdU, 100 mg/kg) was administered twice a day at 5,
      6, and 7 days after stroke. ELISA assays were performed to evaluate the
      specificity of the effect of tadalafil on cGMP. Treatment with tadalafil at a
      dose of 2 or 10 mg/kg significantly improved neurological functional recovery
      compared with saline-treated rats. In addition, tadalafil treatment increased
      cerebral vascular density and the percentage of BrdU-positive endothelial cells
      around the ischemic boundary compared with saline-treated rats. Moreover,
      tadalafil-treated rats showed greater ipsilateral SVZ cell proliferation than
      saline-treated rats. However, treatment with tadalafil did not reduce infarct
      volume when compared to the saline group. Tadalafil selectively increased cGMP
      but not cyclic adenosine monophosphate (cAMP) in brain. Our data demonstrate that
      treatment of ischemic stroke with tadalafil improved functional recovery, which
      was associated with increases of brain cGMP levels and enhancement of
      angiogenesis and neurogenesis.

PMID- 16959228
TI  - Activation of gadolinium-sensitive ion channels in cardiomyocytes in early
      adaptive stages of volume overload-induced heart failure.
AB  - OBJECTIVE: The objective of this study was to investigate whether gadolinium
      (Gd(3+))-sensitive stretch-activated ion channels (SAC) are basally active in
      left ventricular (LV) myocytes in early stages of heart failure (HF) induced by
      volume overload. METHODS: The aortocaval fistula (ACF) model was employed to
      induce HF due to volume overload in rat. At specific time-points, LV myocytes
      were acutely isolated using a modified Langendorff apparatus. Whole-cell currents
      were measured using the patch-clamp technique and intracellular Ca(2+)(Ca(2+)(i))
      was examined using fluorescence imaging and the Ca(2+)-sensitive dye Fura-2.
      RESULTS: Current-voltage data were obtained from sham and ACF myocytes at 5-d and
      2-, 6-, 8- and 10-wk post surgery. Compared to data from matching sham rats, a 10
      microM Gd(3+)-sensitive current at -100 mV comprised a larger fraction of total
      current in myocytes from 5-d, 2-wk, and 6-wk ACF rats. In general, the Gd(3+)
      sensitive current contributed to inward currents at mV< or =-80 and outward
      currents at >+20 mV. The enhanced Gd(3+)-sensitive current was absent in myocytes
      from 8- and 10-wk ACF rats. 10 or 100 microM Gd(3+) had no appreciable effect on
      resting Ca(2+)(i) of myocytes from 5-d ACF or corresponding sham rats. The Gd(3+)
      sensitive current in 5-d ACF myocytes was i) sensitive to the cation-selective
      SAC inhibitor, GsMTx-4, ii) non-selective for Na(+)/K(+), and iii) impermeable to
      Ca(2+). CONCLUSION: A basally-active, Gd(3+)- and GsMTx-4-sensitive SAC current
      that is non-selective for Na(+) and K(+), but impermeable to Ca(2+) under resting
      conditions is transiently elevated in LV myocytes from rats in early stages of
      volume overload-induced HF.

PMID- 16959229
TI  - Genotoxic and antioxidant activities of ethoxyquin salts evaluated by the comet
      assay.
AB  - Four newly synthesized salts of ethoxyquin (EQ: 1,2-dihydro-6-ethoxy-2,2,4
      trimethylquinoline), an antioxidant used in animal feeds, were evaluated with the
      use of the comet assay performed on human lymphocytes: ethoxyquin ascorbate,
      ethoxyquin hexanoate, ethoxyquin salicylate and ethoxyquin salt of Trolox C (6
      hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid). In the study the
      abilities of these compounds to cause DNA fragmentation and to protect against
      H2O2-induced DNA damage were analysed. The obtained results were compared with
      those noted earlier for EQ. After EQ salts treatments (1-25 microM) the genotoxic
      effects were observed, but the genotoxic potentials of the compounds studied were
      lower than that of EQ. On the other hand, EQ salts, similarly to EQ, effectively
      protected the cells from oxidative effect of H2O2. EQ hexanoate was the most
      effective and its antioxidant activity was even slightly higher than that of EQ.
      We suggest that it is worth further detailed studies to estimate its usefulness
      as a preservative.

PMID- 16959230
TI  - Molecular dissection of an hCG-beta epitope using single-step solid phase
      radioimmunoassay.
AB  - BACKGROUND: Peptides and proteins have both sequence-specific (contiguous) and
      conformation-specific (discontiguous) epitopes. Sequence-specific epitopes are
      delineated by peptide approach and other robust methods like competition assays,
      gene expression assays, synthetic peptide library based assays etc. Available
      methods for delineation of conformation-specific epitopes are cumbersome (X-ray
      crystallography etc.), time-consuming and require costly sophisticated
      equipments. Hence, there is a need to develop a simple method for identification
      and mapping of conformation-specific epitopes. METHOD: In the single-step solid
      phase radioimmunoassay (SS-SPRIA), an immunochemical bridge of 'mouse IgG-anti
      mouse IgG' was prepared in the polypropylene wells followed by adsorption with
      hCG specific monoclonal antibody (MAb) G(1)G(10).1. The extent of competitive
      inhibition in binding ability of (125)IhCG-beta with chemically or enzymatically
      modified hCG-beta to immobilized MAb G(1)G(10).1 in comparison to hCG-beta
      standards was utilized to identify the epitopic amino acid involved in epitope
      paratope interaction. RESULTS: Data clearly suggest that the epitope under
      investigation consisted of Arg (94, 95) and Asp (99) at the core region with a
      Lys (104) and a His (106) in the proximity and absence of chymotrypsin
      susceptible Phe or Tyr in this region. CONCLUSION: The data of SS-SPRIA revealed
      the 93-100 loop of amino acid sequence, as the core region of conformation
      specific epitope of hCG-beta at or near the receptor-binding region. Hence, SS
      SPRIA seems to be a simple method for identification and mapping of conformation
      specific epitopes.

PMID- 16959231
TI  - Mineral metabolism in dimethylnitrosamine-induced hepatic fibrosis.
AB  - OBJECTIVES: Complications such as ascites during the pathogenesis of hepatic
      fibrosis and cirrhosis may lead to several abnormalities in mineral metabolism.
      In the present investigation, we have monitored serum and liver concentrations of
      calcium, magnesium, sodium and potassium during experimentally induced hepatic
      fibrosis in rats. DESIGN AND METHODS: The liver injury was induced by
      intraperitoneal injections of dimethylnitrosamine (DMN; N-nitrosodimethylamine,
      NDMA) in doses 1 mg/100 g body weight on 3 consecutive days of each week over a
      period of 21 days. Calcium, magnesium, sodium and potassium were measured by
      atomic absorption spectrophotometry in the serum and liver on days 7, 14 and 21
      after the start of DMN administration. RESULTS: Negative correlations were
      observed between liver function tests and serum mineral levels, except with
      albumin. Calcium, magnesium, potassium and sodium concentrations in the serum
      were decreased after the induction of liver injury. The liver calcium content was
      increased after DMN treatment. No change occurred in liver sodium content.
      However, magnesium and potassium content was significantly reduced in the hepatic
      tissue. CONCLUSIONS: The results suggest that DMN-induced hepatic fibrosis plays
      certain role in the alteration of essential elements. The low levels of albumin
      and the related ascites may be one of the major causes of the imbalance of
      mineral metabolism in hepatic fibrosis and further aggravation of the disease.

PMID- 16959232
TI  - L-cysteine supplementation protects the erythrocyte glucose-6-phosphate
      dehydrogenase activity from reduction induced by forced training.
AB  - BACKGROUND: L-cysteine (L-cys) is implicated in the reduction of free radical
      production. AIM: To investigate the effect of training and L-cys supplementation
      on the erythrocyte glucose-6-phosphate dehydrogenase (G6PD) activity. METHODS:
      Blood was obtained from 10 basketball players pre-game (group A), post-game
      (group B) and after 1 week on L-cys (0.5 g/24 h orally) supplementation pre-
      (group C) and post-training (group D). Total antioxidant status (TAS) and G6PD
      activity were evaluated with commercial kits. RESULTS: TAS increased in the
      groups with l-cys addition (group C and group D). Post-exercise, TAS and G6PD
      activity were remarkably higher (1.48+/-0.12 mmol/L, 8.9+/-1.7 U/g Hb,
      respectively) in group D than those in group B (0.92+/-0.10 mmol/L, 4.8+/-1.6 U/g
      Hb, p<0.01). G6PD activity positively correlated with TAS (r=0.70, p<0.001 pre-
      and r=0.61, p<0.001 post-training) in all the studied groups. CONCLUSIONS: G6PD
      activity is lowered by training probably due to free radical action. L-cys
      supplementation may protect G6PD activity from reduction by increasing total
      antioxidant capacity and glutathione production. G6PD activity should be
      evaluated in the blood of athletes of Mediterranean origin and female G6PD
      deficient heterozygotes.

PMID- 16959233
TI  - Total plasma homocysteine values among elderly subjects: findings from the
      Maracaibo Aging Study.
AB  - OBJECTIVES: The present study generated baseline data for total homocysteine
      (tHcy) in elderly Caribbeans of Hispanic ancestry, residing in Venezuela, their
      country of origin. DESIGN AND METHODS: 2106 participants in the Maracaibo Aging
      Study (MAS), older than 55 years, underwent standardized clinical and laboratory
      assessments, including measurement of plasma tHcy levels, folate, and vitamin B12
      in fasting samples. RESULTS: tHcy concentration in the healthy, normative group
      ranged from 4.1 to 31.8 micromol/L, with a median of 11.5+/-4.7 micromol/L. tHcy
      level increased with age, was significantly higher in men than in women, and
      exhibited inverse correlations with folate and vitamin B12. CONCLUSIONS: tHcy
      levels of the MAS participants were generally higher than levels previously
      reported for community-dwelling elderly populations from other countries. The
      normative centile curves for tHcy can be used in disease risk analysis for this
      population, and possibly for other Hispanic populations residing in the
      Caribbean.

PMID- 16959234
TI  - In vivo analysis reveals a critical role for neuropilin-1 in cranial neural crest
      cell migration in chick.
AB  - The neural crest provides an excellent model system to study invasive cell
      migration, however it is still unclear how molecular mechanisms direct cells to
      precise targets in a programmed manner. We investigate the role of a potential
      guidance factor, neuropilin-1, and use functional knockdown assays, tissue
      transplantation and in vivo confocal time-lapse imaging to analyze changes in
      chick cranial neural crest cell migratory patterns. When neuropilin-1 function is
      knocked down in ovo, neural crest cells fail to fully invade the branchial
      arches, especially the 2nd branchial arch. Time-lapse imaging shows that
      neuropilin-1 siRNA transfected neural crest cells stop and collapse filopodia at
      the 2nd branchial arch entrances, but do not die. This phenotype is cell
      autonomous. To test the influence of population pressure and local environmental
      cues in driving neural crest cells to the branchial arches, we isochronically
      transplanted small subpopulations of DiI-labeled neural crest cells into host
      embryos ablated of neighboring, premigratory neural crest cells. Time-lapse
      confocal analysis reveals that the transplanted cells migrate in narrow, directed
      streams. Interestingly, with the reduction of neuropilin-1 function, neural crest
      cells still form segmental migratory streams, suggesting that initial neural
      crest cell migration and invasion of the branchial arches are separable
      processes.

PMID- 16959235
TI  - Pbx proteins cooperate with Engrailed to pattern the midbrain-hindbrain and
      diencephalic-mesencephalic boundaries.
AB  - Pbx proteins are a family of TALE-class transcription factors that are well
      characterized as Hox co-factors acting to impart segmental identity to the
      hindbrain rhombomeres. However, no role for Pbx in establishing more anterior
      neural compartments has been demonstrated. Studies done in Drosophila show that
      Engrailed requires Exd (Pbx orthologue) for its biological activity. Here, we
      present evidence that zebrafish Pbx proteins cooperate with Engrailed to
      compartmentalize the midbrain by regulating the maintenance of the midbrain
      hindbrain boundary (MHB) and the diencephalic-mesencephalic boundary (DMB).
      Embryos lacking Pbx function correctly initiate midbrain patterning, but fail to
      maintain eng2a, pax2a, fgf8, gbx2, and wnt1 expression at the MHB. Formation of
      the DMB is also defective as shown by a caudal expansion of diencephalic epha4a
      and pax6a expression into midbrain territory. These phenotypes are similar to the
      phenotype of an Engrailed loss-of-function embryo, supporting the hypothesis that
      Pbx and Engrailed act together on a common genetic pathway. Consistent with this
      model, we demonstrate that zebrafish Engrailed and Pbx interact in vitro and that
      this interaction is required for both the eng2a overexpression phenotype and
      Engrailed's role in patterning the MHB. Our data support a novel model of
      midbrain development in which Pbx and Engrailed proteins cooperatively pattern
      the mesencephalic region of the neural tube.

PMID- 16959236
TI  - Genetic organization and embryonic expression of the ParaHox genes in the sea
      urchin S. purpuratus: insights into the relationship between clustering and
      colinearity.
AB  - The ANTP family of homeodomain transcription factors consists of three major
      groups, the NKL, the extended Hox, and the Hox/ParaHox family. Hox genes and
      ParaHox genes are often linked in the genome forming two clusters of genes, the
      Hox cluster and the ParaHox cluster, and are expressed along the major body axis
      in a nested fashion, following the relative positions of the genes within these
      clusters, a property called colinearity. While the presences of a Hox cluster and
      a ParaHox cluster appear to be primitive for bilaterians, few taxa have actually
      been examined for spatial and temporal colinearity, and, aside from chordates,
      even fewer still manifest it. Here we show that the ParaHox genes of the sea
      urchin Strongylocentrotus purpuratus show both spatial and temporal colinearity,
      but with peculiarities. Specifically, two of the three ParaHox genes-discovered
      through the S. purpuratus genome project-Sp-lox and Sp-Cdx, are expressed in the
      developing gut with nested domains in a spatially colinear manner. However,
      transcripts of Sp-Gsx, although anterior of Sp-lox, are detected in the ectoderm
      and not in the gut. Strikingly, the expression of the three ParaHox genes would
      follow temporal colinearity if they were clustered in the same order as in
      chordates, but each ParaHox gene is actually found on a different genomic
      scaffold (>300 kb each), which suggests that they are not linked into a single
      coherent cluster. Therefore, ParaHox genes are dispersed in the genome and are
      used during embryogenesis in a temporally and spatially coherent manner, whereas
      the Hox genes, now fully sequenced and annotated, are still linked and are
      employed as a complex only during the emergence of the adult body plan in the
      larva.

PMID- 16959237
TI  - Essential functions of Alk3 during AV cushion morphogenesis in mouse embryonic
      hearts.
AB  - Accumulated evidence has suggested that BMP pathways play critical roles during
      mammalian cardiogenesis and impairment of BMP signaling may contribute to human
      congenital heart diseases (CHDs), which are the leading cause of infant morbidity
      and mortality. Alk3 encodes a BMP specific type I receptor expressed in mouse
      embryonic hearts. To reveal functions of Alk3 during atrioventricular (AV)
      cushion morphogenesis and to overcome the early lethality of Alk3(-/-) embryos,
      we applied a Cre/loxp approach to specifically inactivate Alk3 in the
      endothelium/endocardium. Our studies showed that endocardial depletion of Alk3
      severely impairs epithelium-mesenchymal-transformation (EMT) in the
      atrioventricular canal (AVC) region; the number of mesenchymal cells formed in
      Tie1-Cre;Alk3(loxp/loxp) embryos was reduced to only approximately 20% of the
      normal level from both in vivo section studies and in vitro explant assays. We
      showed, for the first time, that in addition to its functions on mesenchyme
      formation, Alk3 is also required for the normal growth/survival of AV cushion
      mesenchymal cells. Functions of Alk3 are accomplished through regulating
      expression/activation/subcellular localization of multiple downstream genes
      including Smads and cell-cycle regulators. Taken together, our study supports the
      notion that Alk3-mediated BMP signaling in AV endocardial/mesenchymal cells plays
      a central role during cushion morphogenesis.

PMID- 16959238
TI  - Anteriorward shifting of asymmetric Xnr1 expression and contralateral
      communication in left-right specification in Xenopus.
AB  - Transient asymmetric Nodal signaling in the left lateral plate mesoderm (L LPM)
      during tailbud/early somitogenesis stages is associated in all vertebrates
      examined with the development of stereotypical left-right (L-R) organ asymmetry.
      In Xenopus, asymmetric expression of Nodal-related 1 (Xnr1) begins in the
      posterior L LPM shortly after the initiation of bilateral perinotochordal
      expression in the posterior tailbud. The L LPM expression domain rapidly shifts
      forward to cover much of the flank of the embryo before being progressively
      downregulated, also in a posterior-to-anterior direction. The mechanisms
      underlying the initiation and propagation of Nodal/Xnr1 expression in the L LPM,
      and its transient nature, are not well understood. Removing the posterior tailbud
      domain prevents Xnr1 expression in the L LPM, consistent with the idea that
      normal embryos respond to a posteriorly derived asymmetrically acting positive
      inductive signal. The forward propagation of asymmetric Xnr1 expression occurs
      LPM-autonomously via planar tissue communication. The shifting is prevented by
      Nodal signaling inhibitors, implicating an underlying requirement for Xnr1-to
      Xnr1 induction. It is also unclear how asymmetric Nodal signals are modulated
      during L-R patterning. Small LPM grafts overexpressing Xnr1 placed into the R LPM
      of tailbud embryos induced the expression of the normally L-sided genes Xnr1,
      Xlefty, and XPitx2, and inverted body situs, demonstrating the late-stage
      plasticity of the LPM. Orthogonal Xnr1 signaling from the LPM strongly induced
      Xlefty expression in the midline, consistent with recent findings in the mouse
      and demonstrating for the first time in another species conservation in the
      mechanism that induces and maintains the midline barrier. Our findings suggest
      that there is long-range contralateral communication between L and R LPM,
      involving Xlefty in the midline, over a substantial period of tailbud
      embryogenesis, and therefore lend further insight into how, and for how long, the
      midline maintains a L versus R status in the LPM.

PMID- 16959239
TI  - ADMP2 is essential for primitive blood and heart development in Xenopus.
AB  - We describe here the cloning of a new member of the TGF-beta family with
      similarity to the anti-dorsalizing morphogenetic proteins (ADMPs). This new gene,
      ADMP2, is expressed in a broad band of mesendoderm cells that appear to include
      the progenitors of the endoderm and the ventral mesoderm. Antisense morpholino
      oligonucleotide knockdown of ADMP2 results in near-complete disruption of
      primitive blood and heart development, while the development of other mesoderm
      derivatives, including pronephros, muscle and lateral plate is not disrupted.
      Moreover, the development of the primitive blood in ADMP2 knockdown embryos
      cannot be rescued by BMP. These results suggests that ADMP2 plays an early role
      in specifying presumptive ventral mesoderm in the leading edge mesoderm, and that
      ADMP2 activity may be necessary to respond to BMP signaling in the context of
      ventral mesoderm induction.

PMID- 16959240
TI  - Analysis of talpid3 and wild-type chicken embryos reveals roles for Hedgehog
      signalling in development of the limb bud vasculature.
AB  - Chicken talpid(3) mutant embryos have a wide range of Hedgehog-signalling related
      defects and it is now known that the talpid(3) gene product encodes a novel
      protein essential for Hedgehog signalling which is required for both activator
      and repressor functions of Gli transcription factors (Davey, M.G., Paton, I.R.,
      Yin, Y., Schmidt, M., Bangs, F.K., Morrice, D.R., Gordon-Smith, T., Buxton, P.,
      Stamataki, D., Tanaka, M., Munsterberg, A.E., Briscoe, J., Tickle, C., Burt, D.W.
      (2006). The chicken talpid(3) gene encodes a novel protein essential for Hedgehog
      signalling. Genes Dev 20 1365-77). Haemorrhaging, oedema and other severe
      vascular defects are a central aspect of the talpid(3) phenotype (Ede, D.A. and
      Kelly, W.A (1964a). Developmental abnormalities in the head region of the
      talpid(3) mutant fowl. J. Embryol. exp. Morp. 12:161-182) and, as Hedgehog (Hh)
      signalling has been implicated in every stage of development of the vascular
      system, the vascular defects seen in talpid(3) are also likely to be attributable
      to abnormal Hedgehog signalling. Gene expression of members of the VEGF and
      Angiopoietin families of angiogenic growth factors has been linked to
      haemorrhaging and oedema and we find widespread expression of VEGF-D, rigf and
      Ang2a in the talpid(3) limb. Furthermore, ectopic expression of these genes in
      talpid(3) limbs points to regulation via Gli repression rather than activation.
      We monitored specification of vessel identity in talpid(3) limb vasculature by
      examining expression of artery-specific genes, Np1 and EphrinB2, and the vein
      specific genes, Np2a and Tie2. We show that there are supernumerary subclavian
      arteries in talpid(3) limb buds and abnormal expression of an artery-specific
      gene in the venous submarginal sinus, despite the direction of blood flow being
      normal. Furthermore, we show that Shh can induce Np1 expression but has no effect
      on Np2a. Finally, we demonstrate that induction of VEGF and Ang2a expression by
      Shh in normal limb buds is accompanied by vascular remodelling. Thus Hedgehog
      signalling has a pivotal role in the cascade of angiogenic events in a growing
      embryonic organ which is similar to that proposed in tumours.

PMID- 16959242
TI  - Inhibition of BMP signaling during zebrafish fin regeneration disrupts fin growth
      and scleroblasts differentiation and function.
AB  - The zebrafish caudal fin provides a simple model to study molecular mechanisms of
      dermal bone regeneration. We previously showed that misexpression of Bone
      morphogenetic protein 2b (Bmp2b) induces ectopic bone formation within the
      regenerate. Here we show that in addition to bmp2b and bmp4 another family
      member, bmp6, is involved in fin regeneration. We further investigated the
      function of BMP signaling by ectopically expressing the BMP signaling inhibitor
      Chordin which caused: (1) inhibition of regenerate outgrowth due to a decrease of
      blastema cell proliferation and downregulation of msxb and msxC expression and
      (2) reduced bone matrix deposition resulting from a defect in the maturation and
      function of bone-secreting cells. We then identified targets of BMP signaling
      involved in regeneration of the bone of the fin rays. runx2a/b and their target
      col10a1 were downregulated following BMP signaling inhibition. Unexpectedly, the
      sox9a/b transcription factors responsible for chondrocyte differentiation were
      detected in the non-cartilaginous fin rays, sox9a and sox9b were not only
      differentially expressed but also differentially regulated since sox9a, but not
      sox9b, was downregulated in the absence of BMP signaling. Finally, this analysis
      revealed the surprising finding of the expression, in the fin regenerate, of
      several factors which are normally the signatures of chondrogenic elements during
      endochondral bone formation although fin rays form through dermal ossification,
      without a cartilage intermediate.

PMID- 16959243
TI  - Translational control genes in the sea urchin genome.
AB  - Sea urchin eggs and early cleavage stage embryos provide an example of regulated
      gene expression at the level of translation. The availability of the sea urchin
      genome offers the opportunity to investigate the "translational control" toolkit
      of this model system. The annotation of the genome reveals that most of the
      factors implicated in translational control are encoded by nonredundant genes in
      echinoderm, an advantage for future functional studies. In this paper, we focus
      on translation factors that have been shown or suggested to play crucial role in
      cell cycle and development of sea urchin embryos. Addressing the cap-binding
      translational control, three closely related eIF4E genes (class I, II, III) are
      present, whereas its repressor 4E-BP and its activator eIF4G are both encoded by
      one gene. Analysis of the class III eIF4E proteins in various phyla shows an
      echinoderm-specific amino acid substitution. Furthermore, an interaction site
      between eIF4G and poly(A)-binding protein is uncovered in the sea urchin eIF4G
      proteins and is conserved in metazoan evolution. In silico screening of the sea
      urchin genome has uncovered potential new regulators of eIF4E sharing the common
      eIF4E recognition motif. Taking together, these data provide new insights
      regarding the strong requirement of cap-dependent translation following
      fertilization. The genome analysis gives insights on the complexity of eEF1B
      structure and motifs of functional relevance, involved in the translational
      control of gene expression at the level of elongation. Finally, because
      deregulation of translation process can lead to diseases and tumor formation in
      humans, the sea urchin orthologs of human genes implicated in human diseases and
      signaling pathways regulating translation were also discussed.

PMID- 16959241
TI  - Beta-catenin is essential for lamination but not neurogenesis in mouse retinal
      development.
AB  - During vertebrate retinal development, the seven retinal cell types differentiate
      sequentially from a single population of retinal progenitor cells (RPCs) and
      organize themselves into a distinct laminar structure. The purpose of this study
      was to determine whether beta-catenin, which functions both as a nuclear effector
      for the canonical Wnt signaling pathway and as a regulator of cell adhesion, is
      required for retinal neurogenesis or lamination. We used the Cre-loxP system to
      either eliminate beta-catenin or to express a constitutively active form during
      retinal neurogenesis. Eliminating beta-catenin did not affect cell
      differentiation, but did result in the loss of the radial arrangement of RPCs and
      caused abnormal migration of differentiated neurons. As a result, the laminar
      structure was massively disrupted in beta-catenin-null retinas, although all
      retinal cell types still formed. In contrast to other neural tissues, eliminating
      beta-catenin did not significantly reduce the proliferation rate of RPCs;
      likewise, activating beta-catenin ectopically in RPCs did not result in
      overproliferation, but loss of neural retinal identity. These results indicate
      that beta-catenin is essential during retinal neurogenesis as a regulator of cell
      adhesion but not as a nuclear effector of the canonical Wnt signaling pathway.
      The results further imply that retinal lamination and retinal cell
      differentiation are genetically separable processes.

PMID- 16959244
TI  - Antidepressant properties of rotigotine in experimental models of depression.
AB  - Limited clinical data are available on the use of dopamine agonists for the
      control of motor function and also for the treatment of depression. This study
      was performed to evaluate the potential effects of the dopamine receptor agonist
      rotigotine in rat models of anxiety and depression. After repeated administration
      at doses of 0.05, 0.5, 1, and 5 mg/kg, rotigotine increased spontaneous motor
      activity at the 5 mg/kg dose after 3-5 days of treatment. At lower doses, the
      drug had no effect on locomotor activity. After a single administration,
      rotigotine had no anxiolytic activity in rats during the elevated plus-maze test
      or the Geller-Seifter conflict test. In the behavioral despair test (also known
      as the forced swim test), the 5 mg/kg dose of rotigotine enhanced the mobility of
      rats. Rotigotine (0.5, 1, and 5 mg/kg/day for 5 days) reversed the active
      avoidance deficit of helpless rats in the learned helplessness test, as shown by
      a significant decrease in escape failures after 3 to 4 days (0.5 mg/kg/day), 5
      days (1 mg/kg/day), and 3 to 5 days (5 mg/kg/day) of treatment. During open-field
      testing of rats subjected to olfactory bulbectomy and given a 14-day schedule of
      rotigotine (0.3 mg/kg every 2 days), hyperactivity reversed according to a U
      shaped dose-response curve. These results suggest that rotigotine may have
      antidepressant properties at doses of 1 mg/kg and lower. Potential effects at
      doses of 5 mg/kg and higher may be masked by an effect of the compound whereby
      general locomotor activity is enhanced.

PMID- 16959245
TI  - Nuclear and mitochondrial localization of the putative RNA helicase DHX32.
AB  - RNA helicases are involved in all aspects of RNA metabolism. We identified DHX32
      as a novel gene with homology to the DHX family of RNA helicases. To gain insight
      into the role of DHX32 in RNA metabolism, we determined its subcellular
      localization. Electron microscopy immunocytochemistry detected DHX32 in the
      nucleus and mitochondria of the myeloid leukemia cell line HL-60. Confocal
      microscopy shows mitochondrial localization of DHX32 in HeLa cells. Double
      labeling showed close proximity of DHX32 to some of the newly synthesized RNA in
      the mitochondria. These results suggest that DHX32 is a putative RNA helicase
      that might be involved in regulating nuclear and mitochondrial gene expression.

PMID- 16959246
TI  - Chronic idiopathic myelofibrosis (CIMF) resulting from a unique 3;9 translocation
      disrupting the janus kinase 2 (JAK2) gene.
AB  - We report a case of t(3;9)(q21;p24) in a patient with chronic idiopathic
      myelofibrosis (CIMF), a chronic myeloproliferative disorder (CMPD), initially
      detected by G-banding and fluorescent in situ hybridization (FISH) in an
      unstimulated culture of peripheral blood. Subsequent cytogenetic studies of bone
      marrow aspirates showed the presence and persistence of the same translocation.
      No additional cytogenetic abnormalities were found. This appears to be a unique
      translocation that has not been previously reported in the English literature,
      although both breakpoints, 3q21 and 9p24, are well known cancer-related
      breakpoints. The former is the mapped location of the ribophorin 1 (RPN1) gene,
      whereas the latter is the mapped location of the janus kinase 2 (JAK2) gene. This
      raises the possibility that disruption of one or both loci at the breakpoints of
      the presently described structural chromosomal rearrangement may be the primary
      event leading to the initiation and development of the hematopoietic disorder in
      this patient. It is not unreasonable to hypothesize that the juxtaposition of the
      RPN1 gene on 3q21 with the JAK2 gene on 9p24 leads to enhanced JAK2 activity.
      Additional studies will be needed to provide further support for or to disprove
      this hypothesis. To the best of our knowledge, this is the first reported case of
      CIMF associated with a reciprocal 3;9 translocation with the 3q21 and 9p24
      breakpoints. The elucidation of the mechanism of leukemogenesis in CIMF may one
      day lead to successful targeted therapy in this hematopoietic disorder. It may
      also shed additional light on the diagnosis, prognosis and treatment of certain
      other cancers with similar genetic etiologies.

PMID- 16959247
TI  - Regulation of cytokinesis by mgcRacGAP in B lymphocytes is independent of GAP
      activity.
AB  - In cytokinesis, several molecules including small G proteins and their regulators
      are known to have important roles. One of these regulators, mgcRacGAP has GTPase
      activating protein (GAP) activity for Rac, Cdc42 and Rho. MgcRacGAP has also been
      shown to be involved in cytokinesis using various cell types. However, the
      requirement of mgcRacGAP for cytokinesis and survival in B lymphocytes has not
      been fully examined. Here, we demonstrate that normal cytokinesis in B
      lymphocytes requires the GAP and NH2 terminal domains but not GAP activity of
      mgcRacGAP. In addition, we report that apoptosis induced by conditional ablation
      of mgcRacGAP in the B cell line is fully rescued by the introduction of a GAP
      inactive mutant, suggesting that the survival defect in mgcRacGAP-deficient B
      cells is also independent of GAP activity.

PMID- 16959248
TI  - Inhibition of TNF-alpha reduces laser-induced choroidal neovascularization.
AB  - To investigate the role of the TNF-alpha in the development of laser-induced
      choroidal neovascularization (CNV) in a mouse model. Four separate laser burns
      were applied to induce ruptures of Bruch's membrane and subsequent choroidal
      neovascularization in C57BL/6J mice. TNF-alpha protein expression was
      semiquantitatively assessed by Western blot analysis of the choroidal and RPE
      layer from mice with or without laser treatment. To investigate the effect of TNF
      alpha inhibition on CNV formation, animals were treated for 7 days via
      intraperitonealy implanted osmotic pumps either 3 days before or after laser
      injury with recombinant TNF receptor P75 (etanercept), a chimeric monoclonal
      antibody (infliximab), or a purified rat anti-mouse/rat TNF monoclonal antibody
      (TNF-mAb), respectively. Fluorescein angiography, flat-mount preparations, and
      histopathology were performed at day 7, 10, or 14 after laser treatment. Western
      blotting demonstrated that TNF-alpha expression was 4.57-fold higher in the
      choroid and RPE one week after laser injury compared to control mice without
      laser. When evaluated one and two weeks after laser injury, etanercept and
      infliximab given from the 3rd day before laser-damage significantly reduced CNV
      size and pathological fluorescein leakage compared to the control group after
      laser treatment only. The inhibitory effect of the monoclonal TNF-alpha antibody
      on CNV formation was evident two weeks after photocoagulation but not after one
      week. Only etanercept administered 3 days after laser injury still reduced
      significantly the development of CNV lesions. Histopathology confirmed that CNV
      lesions in treated mice were smaller in size compared to the control animals
      without TNF inhibitor treatment. In conclusion, anti-TNF-alpha treatment with
      different inhibitors reduces both the size and the leakage of laser-induced CNV.
      These results suggest the involvement of TNF-alpha in the development of laser
      induced CNV and its potential use as a therapeutic agent in the age-related
      macular degeneration.

PMID- 16959249
TI  - Molecular events in early development of the ciliary body: a question of folding.
AB  - Ciliary body morphogenesis is a complicated, multi-step process requiring
      coordinated changes in cell shape, flexure of epithelial sheets and dynamic
      shifts in mitotic rates. Very little is known of how these cellular events are
      triggered or regulated. This review summarises current models of ciliary body
      morphogenesis. The role of intraocular pressure as a driver of morphogenesis is
      re-evaluated in the light of new information. An update on the role of the lens
      in ciliary body morphogenesis is presented. In the second part of the review
      current gene expression data is related to ciliary body morphogenesis. In
      particular the role of Bmp4 and its downstream target genes are discussed, with
      novel gene expression patterns of Bmp4 and Tgfbeta1i4 being presented.

PMID- 16959250
TI  - PGI2 opens potassium channels in retinal pericytes by cyclic AMP-stimulated,
      cross-activation of PKG.
AB  - Pericytes exert an important influence on the control of retinal blood flow;
      however, little is known regarding the molecular basis of retinal pericyte
      excitability. The purpose of this study was to elucidate the signaling pathway of
      how prostacyclin (PGI2), an important endogenous regulator of retinal blood flow,
      stimulates potassium channel activity in retinal pericytes. Retinal pericytes
      were isolated from porcine eyeballs and plated on glass coverslips.
      Immunocytochemistry was performed to verify expression of the pericyte-specific
      ganglioside marker, 3G5 and smooth muscle alpha-actin. Activity of the large
      conductance, voltage- and calcium-activated potassium (BKCa) channel was measured
      in retinal pericytes via single-channel patch-clamp, and channel identification
      was confirmed via biophysical and pharmacological characterization. PGI2 (10
      microM) or beraprost (30 microM; more stable prostacyclin analog) dramatically
      stimulated the activity of BKCa channels isolated in cell-attached patches. These
      experiments strongly suggested that PGI2 stimulated BKCa channel activity via a
      diffusible second messenger. Similarly, chlorophenylthio (CPT)-cAMP (100 microM;
      membrane permeable cAMP derivative) induced a significant increase in BKCa
      channel activity; however, inhibition of the cAMP-dependent protein kinase (PKA)
      with 300 nM KT5720 could not reverse the stimulatory effect of either PGI2 or CPT
      cAMP. In contrast, activation of BK(Ca) channels with either CPT-cAMP or PGI2 was
      abolished by 300 nM KT5823 (n=5, p<0.01), an inhibitor of the cGMP-dependent
      protein kinase (PKG). In addition, PGI2-stimulated channel activity was also
      attenuated by Rp-8-CPT-cGMPS, which inhibits PKG activity via a different
      mechanism. These findings demonstrate that prostacyclin, the most abundant
      prostanoid in the retinal circulation, is a potent stimulator of BKCa channel
      activity in retinal pericytes. Interestingly, this response appears to involve
      cAMP-stimulated cross-activation of PKG, and not PKA. Taken together, these
      findings could explain, at least in part, the cellular/molecular basis for PGI2
      induced pericyte relaxation and augmentation of blood flow in the retina.
      Further, we propose PKG-dependent stimulation of BKCa channel activity as a new
      potential therapeutic target to combat decreased retinal blood flow seen in some
      disease states (e.g., diabetic retinopathy).

PMID- 16959251
TI  - Blocking EphA4 upregulation after spinal cord injury results in enhanced chronic
      pain.
AB  - Spinal cord injury (SCI) is characterized by a total or partial loss of motor and
      sensory functions due to the inability of neurons to regenerate. This lack of
      axonal regenerative response has been associated with the induction of inhibitory
      proteins for regeneration, such as the Eph receptor tyrosine kinases. One member
      of this family, the EphA4 receptor, coordinates appropriate corticospinal fibers
      projections during early development and is expressed in spinal commissural
      interneurons. Its mechanism of action is mediated by repulsive activity after
      ligand binding, but its role after trauma is unknown. We examined the temporal
      expression profile of this receptor after spinal cord contusion in adult rats by
      RT-PCR and immunohistochemistry. SCI induced a biphasic gene expression profile
      with an initial downregulation at 2 and 4 days post-injury (DPI) followed by a
      subsequent upregulation. Double labeling studies localized EphA4 immunoreactivity
      in neurons from the gray matter and astrocytes of the white matter. To test the
      role of this receptor, we reduced gene upregulation by intrathecal/subdural
      infusion of EphA4-antisense oligodeoxynucleotide (ODN) and subsequently assessed
      behavioral outcomes. No locomotor recovery was observed in the rats treated with
      the EphA4-antisense ODN. Interestingly, reducing EphA4 expression increased
      mechanical allodynia, as observed by the Von Frey test and decreased exploratory
      locomotor activity. These results indicate that upregulation of EphA4 receptor
      after trauma may prevent the development of abnormal pain syndromes and could
      potentially be exploited as a preventive analgesic mediator to chronic
      neuropathic pain.

PMID- 16959252
TI  - Rice embryogenic calli express a unique set of microRNAs, suggesting regulatory
      roles of microRNAs in plant post-embryogenic development.
AB  - In vitro cultured embryogenic callus was employed as a model to investigate
      microRNAs (miRNAs) associated with embryogenesis and post-embryonic development.
      Thirty-one miRNAs including 16 novel species were identified from a large number
      of small RNAs which were cloned from both differentiated and undifferentiated
      rice embryogenic calli. Four target genes of the miRNAs were further validated. A
      set of the miRNAs, including miR397 and miR156, exhibited intriguing expression
      patterns during the transition from undifferentiated to differentiated calli. By
      exploiting the correlations between the differential expression patterns of these
      miRNAs and their targets, the regulatory roles of the miRNAs on meristem
      maintenance and embryogenesis were indicated.

PMID- 16959253
TI  - Linking steroid hormone levels to sexual maturity index and energy reserves in
      Nereis diversicolor from clean and polluted estuaries.
AB  - The objective of this work was to compare seasonal variations of reproduction
      physiology of the ragworm Nereis diversicolor --a key species in estuarine
      ecosystems--originating from a clean (Authie) and multi-polluted (Seine)
      estuaries. A particular attention was carried out in female worms, on
      relationships between sexual maturity stages, energy reserves (glycogen and
      lipids) and steroid hormone levels (progesterone, 17beta-estradiol, and
      testosterone). Sexual maturity index (SMI), energy reserves and steroid hormones
      are clearly influenced by season in worms from both sites. Depleted steroid
      hormone levels were depicted in specimens exhibiting high sexual maturity stage
      and energy reserves. Intersite analysis has revealed all over the sampling
      period:--a sexual precocity in worms from Seine,--glycogen concentrations
      generally higher in worms from Authie,--no clear tendency for lipids,--no
      differences in steroid hormone levels. Sexual precocity and lower glycogen levels
      in Seine could be explained by a specific strategy above all devoted to
      reproduction in these worms. Chemical stress could be a possible explanation of
      these observations.

PMID- 16959254
TI  - Distribution of gonadotropin releasing-hormone-II in the house sparrow brain
      (Passer domesticus).
AB  - In songbirds, three isoforms of gonadotropin-releasing hormone (GnRH) have been
      reported: chicken GnRH-I (GnRH-I); and -II (GnRH-II); and lamprey GnRH-III (lGnRH
      III). In galliformes, the distribution of GnRH-I and -II have been extensively
      studied. GnRH-I cell bodies are located primarily in the preoptic-septal region
      and primarily project to the median eminence. GnRH-II cell bodies are located in
      the midbrain and project to various hypothalamic and extrahypothalamic regions.
      In songbirds, the distributions of only GnRH-I and lGnRH-III have been thoroughly
      described. Songbirds differ from galliformes in that they possess specialized
      neural regions for the learning and production of complex vocalizations, the song
      control system. In songbirds lGnRH-III was found within many song nuclei. In this
      study, we investigated the distribution of GnRH-II in the male house sparrow
      (Passer domesticus) brain. Our objectives were (1) to determine the distribution
      of GnRH-II in the male songbird brain and (2) to investigate the presence of GnRH
      II in song control nuclei. Our study identified immunoreactive magnocellular GnRH
      II cell bodies in the oculomotor region of the mesencephalon and parvicellular
      cells in the lateral hypothalamus. Also, an extensive network of GnRH-II
      immunoreactive fibres was observed in hypothalamic nuclei and extrahypothalamic
      regions. Immunoreactive GnRH-II fibres were most abundant in the preoptic area,
      ventromedial nucleus, hippocampus and the medial septum. Sparse immunoreactivity
      was also observed in the mesencephalon and diencephalon. GnRH-II was not
      identified in any of the song-control nuclei. Unlike lGnRH-III, these data
      suggest that GnRH-II is not directly involved with song learning, perception or
      production.

PMID- 16959255
TI  - Study of proteins associated with the Eimeria tenella refractile body by a
      proteomic approach.
AB  - Refractile bodies (RB), whose function is still unknown, are specific structures
      of Eimeriidae parasites. In order to study their proteome, RB were purified from
      Eimeria tenella sporozoites by a new procedure using a reversible fixation
      followed by centrifugation. RB proteins were resolved by two-dimensional
      electrophoresis. Around 76 and 89 spots were detected on RB two-dimensional gels
      using gradients in the 3-10 and 4-7 range, respectively. RB proteins were located
      mainly between pH 5 and 7. RB gels were then compared with previously established
      maps of the entire sporozoite proteome. Proteins appearing in new spots were
      identified by mass spectrometry. Thirty protein isoforms were located in RB.
      Added to the already known RB proteins such as Eimepsin and SO7', the new RB
      proteins were defined as haloacid dehalogenase, hydrolase, subtilase, lactacte
      dehydrogenase or ubiquitin family proteins. The RB proteome analysis confirmed
      the hypothesis that this structure is a reservoir for proteins necessary to
      invasion but also suggests that RB have energetic and metabolic functions.

PMID- 16959256
TI  - A theoretical basis for parameter selection and instrument design in
      comprehensive size-exclusion chromatography x liquid chromatography.
AB  - A novel approach for the selection of the operational parameters (linear
      velocity, column length) for a comprehensive 2D-LC system is discussed. Starting
      point for the calculations is a given second dimension ((2)D) separation and a
      desired peak capacity for the 2D system. Using the theory developed here the
      optimum settings for the first dimension ((1)D) column can be derived. Theory
      clearly indicates that the choice of the (1)D conditions is basically limited to
      just one set of column lengths and linear velocities. The new method is tested on
      a comprehensive two-dimensional liquid chromatography system which uses size
      exclusion chromatography (SEC) followed by reversed phase liquid chromatography
      (RPLC). A novel LC/LC interface, using a six-port valve rather than storage
      loops, joins the two chromatographic dimensions. From a theoretical comparison of
      continuous low flow and stop-flow operation the latter method was found to be an
      attractive mode of interfacing. The common idea that stop-flow operation results
      in additional band broadening is shown to be incorrect. The new interface design
      operated in the stop-flow mode permits the use of conventional analytical
      diameter HPLC columns, 7.8mm for SEC and 4.6mm for RPLC. The reversed phase
      chromatography utilizes a monolithic C-18 modified silica column, which produces
      fast and efficient analyses. As test samples complex mixtures of peptides were
      analyzed.

PMID- 16959257
TI  - Prediction of theoretical plate number in isothermal gas chromatographic analysis
      on capillary columns.
AB  - A method for the prediction of the efficiency of gas chromatographic analysis in
      isothermal conditions by using experimental data of 1-alcohols and n-alkanes
      measured on capillary columns filled with polar and non-polar stationary phases
      in isothermal and isobaric conditions is described. The theoretical plate height
      trend indicates the change of separation efficiency as a function of inlet
      pressure and column temperature. By evaluating the variation of the diffusion
      coefficients of the analysed compounds into the mobile and stationary phase it is
      possible to predict the column efficiency and the number of theoretical plates at
      any temperature.

PMID- 16959258
TI  - Comparison of fetal and maternal inflammatory responses in the ovine placenta
      after experimental infection with Chlamydophila abortus.
AB  - Placentae from 13 pregnant ewes infected intravenously with Chlamydophila
      abortus, together with placentae from nine uninfected control ewes, were examined
      at 14, 21 or 28 days post-inoculation (p.i.). Chlamydial inclusions were present
      in the trophoblast at 14 days p.i. and were widespread by 21 days p.i.
      Chorioallantoic lesions (oedema, arteritis and thrombosis) were severe at 28 days
      p.i., the changes being particularly marked in the membrane surrounding
      placentomes. Lymphocytes constituted only a small proportion of the cellular
      infiltrate in the chorioallantois; neutrophil infiltration of the chorionic
      surface was evident where the trophoblast layer had sloughed, whereas macrophages
      represented the predominant cell type in the deeper stroma. In contrast, on the
      maternal side of the placenta, chlamydial inclusions were sparse at all
      timepoints, and even at 28 days p.i., lesions were restricted to focal
      endometritis at the placentomal limbus and occasional foci of septal necrosis. T
      lymphocytes were numerous within endometrial and septal lesions, the infiltrate
      consistently containing more CD8(+) than CD4(+) cells. The fetal response to
      chlamydial invasion of the placenta was innate in character, whereas the maternal
      response appeared to represent an acquired, chlamydia-specific immune response.

PMID- 16959259
TI  - Relationship between canine visceral leishmaniosis and the Leishmania
      (Leishmania) chagasi burden in dermal inflammatory foci.
AB  - The skin is the first point of contact with organisms of the genus Leishmania
      from sand fly vectors, and apparently normal skin of sick dogs harbours
      amastigote forms of Leishmania chagasi. In relation to canine visceral
      leishmaniosis (CVL), the ear skin was examined in 10 uninfected dogs (UDs) and in
      31 dogs dogs naturally infected with L. chagasi. The infected animals consisted
      of 10 symptomless dogs (SLDs), 12 mildly affected dogs (MADs) and nine affected
      dogs (ADs). A higher parasite burden was demonstrated in ADs than in SLDs by anti
      Leishmania immunohistochemistry (P<0.01), and by Leishman Donivan Unit (LDU)
      indices (P=0.0024) obtained from Giemsa-stained impression smears. Sections
      stained with haematoxylin and eosin demonstrated a higher intensity of
      inflammatory changes in ADs than in SLDs (P<0.05), and in the latter group flow
      cytometry demonstrated a correlation (P=0.05/r=0.7454) between the percentage of
      CD14(+) monocytes in peripheral blood and chronic dermal inflammation.
      Extracellular matrix assessment for reticular fibres by staining of sections with
      Masson trichrome and Gomori ammoniacal silver demonstrated a decrease in collagen
      type I and an increase in collagen type III as the clinical signs increased. The
      data on correlation between cellular phenotypes and histological changes seemed
      to reflect cellular activation and migration from peripheral blood to the skin,
      mediated by antigenic stimulation. The results suggested that chronic dermal
      inflammation and cutaneous parasitism were directly related to the severity of
      clinical disease.

PMID- 16959260
TI  - Distribution of leucocyte subsets in the canine pharyngeal tonsil.
AB  - This report describes the distribution and nature of lymphoid tissue in the
      nasopharyngeal mucosa of six puppies (mean age+/-SD, 0.3+/-0.25 years) and eight
      adult dogs (mean age+/-SD, 8.8+/-2.67 years) without respiratory disease. A non
      encapsulated area of organized mucosa-associated lymphoid tissue was observed in
      the caudal part of the posterior wall of the nasopharynx, distal to the openings
      of the auditory tubes. This structure was consistent with the pharyngeal tonsil
      and was microscopically more extensive in puppies than in adult dogs.
      Histochemistry and immunohistochemistry were used to characterize and enumerate
      the leucocyte subsets in this part of the nasopharynx. Mast cells were found
      immediately beneath the respiratory epithelium but were also scattered in the
      glandular and muscular tissue. IgA(+) plasma cells outnumbered IgG(+) and IgM(+)
      plasma cells, especially in the glandular tissue. All classes of plasma cells
      were present in significantly greater numbers in adults than in puppies. MHC
      class II(+) cells were mainly observed in areas containing diffuse and follicular
      aggregates of lymphoid cells. Both MHC class II(+) cells and CD1c(+) cells with a
      dendritic morphology were predominantly found immediately beneath or within the
      epithelium, and cells expressing these markers were more abundant in puppies than
      in adult dogs. The anti-L1 marker labelled low numbers of cells with a
      neutrophilic morphology, which were significantly more abundant in puppies than
      in adult dogs. The majority of lymphoid cells were CD3(+) T lymphocytes and these
      were particularly abundant in areas containing aggregates of lymphoid cells;
      CD4(+), CD8(+) and TCR alphabeta(+) cells had the same distribution as the CD3(+)
      cells. CD4(+) cells were more numerous than CD8(+) cells. The quantitative and
      qualitative data obtained will enable comparisons to be made with similar studies
      in dogs suffering from nasopharyngeal diseases, or when the local immune system
      needs to be investigated.

PMID- 16959261
TI  - Detection of memory B lymphocytes specific to hepatitis B virus (HBV) surface
      antigen (HBsAg) from HBsAg-vaccinated or HBV-immunized subjects by ELISPOT assay.
AB  - To improve the investigation of the role of human memory B lymphocytes following
      hepatitis B virus (HBV) infection or vaccination, we developed a method to
      characterize circulating memory B cells specific to hepatitis B surface antigen
      (HBsAg). Our approach combined: (1) purification of CD19+ cells, (2) CD40-CD40L
      polyclonal stimulation, and (3) enumeration of memory B cells differentiated into
      anti-HBs antibody (Ab)-secreting cells (HBs-SCs) by a HBs-ELISPOT assay. In this
      way, HBs-SCs were detected in 17 HBsAg-vaccinated and nine HBV-immunized subjects
      including four individuals with serum anti-HBs Ab levels < 10 mIU/ml, but not in
      six controls. IgG+, IgA+ plus IgM+ HBs-SCs, representing 5-1736 cells/10(6)
      circulating B cells and 0.02-0.58% of total immunoglobulin-SCs generated by the B
      cell polyclonal stimulation, were counted by an Ig two-colour ELISPOT assay. In
      addition, anti-HBs Abs were found in 8/15 supernatants recovered from B cell
      cultures which contained HBs-SCs, suggesting that the HBs-ELISPOT assay is more
      reliable in tracking HBsAg-specific memory B cells than ELISA measurement of anti
      HBs Abs secreted in supernatants. This new approach could be useful to explore
      the presence and the longevity of HBsAg-specific memory B cells in vaccinated and
      immunized subjects, in chronic HBV infection and after liver transplantation for
      HBV-related disease.

PMID- 16959262
TI  - Statistical positivity criteria for the analysis of ELISpot assay data in HIV-1
      vaccine trials.
AB  - The enzyme-linked immunospot (ELISpot) assay is one of the leading technologies
      used to measure cellular responses in many settings including HIV vaccine
      clinical trials. HIV-1-specific effector T lymphocyte responses are considered
      necessary in the control of infection. Accurate measurement and summary of
      cellular immune responses are critical to HIV research. ELISpot assay readout is
      often dichotomized into positive/negative responses according to some pre
      specified criteria. Given the increase in the number of replicates used for each
      stimulation with current assay configurations in the HIV Vaccine Trials Network
      (HVTN) laboratories, a new approach is now possible. We propose an objective
      criteria based on a hypothesis-driven method that controls the false positive
      rate while maintaining sensitivity to each of the antigen-specific responses
      under study. The new approach is compared to other commonly employed criteria
      using real and simulated data.

PMID- 16959263
TI  - NMR-based model reveals the structural determinants of mammalian arylamine N
      acetyltransferase substrate specificity.
AB  - Arylamine N-acetyltransferases (NATs) catalyze the acetylation of arylamines, a
      key step in the detoxification of many carcinogens. The determinants of NAT
      substrate specificity are not known, yet this knowledge is required to understand
      why NAT enzymes acetylate some arylamines, but not others. Here, we use NMR
      spectroscopy and homology modeling to reveal the structural determinants of
      arylamine acetylation by NATs. In particular, by using chemical shift
      perturbation analysis, we have identified residues that play a critical role in
      substrate binding and catalysis. This study reveals why human NAT1 acetylates the
      sunscreen additive p-aminobenzoic acid and tobacco smoke carcinogen 4
      aminobiphenyl, but not o-toluidine and other arylamines linked to bladder cancer.
      Our results represent an important step toward predicting whether arylamines
      present in new products can be detoxified by mammalian NATs.

PMID- 16959264
TI  - Mechanism by which the amyloid-like fibrils of a beta 2-microglobulin fragment
      are induced by fluorine-substituted alcohols.
AB  - Although the formation of an alpha-helix or partial unfolding of proteins has
      been suggested to be important for amyloid fibrils to form in alcohols, the exact
      mechanism involved remains elusive. To obtain further insight into the
      development of amyloid fibrils, we used a 22-residue peptide, K3, corresponding
      to Ser20 to Lys41 of intact beta2-microglobulin. Although K3 formed an alpha
      helix at high concentrations of 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3
      hexafluoroisopropanol (HFIP) in 10 mM HCl (pH approximately 2), the helical
      content was not high, indicating a low preference to do so. The partly alpha
      helical conformation was converted with time into a highly ordered beta-sheet
      with a fibrillar morphology as revealed by atomic force microscopy. Importantly,
      the TFE and HFIP-induced fibrillation exhibited a concentration dependence with a
      maximum at approximately 20 and approximately 10% (v/v), respectively, slightly
      below the concentrations at which these alcohols form dynamic clusters. Focusing
      on the similarity of the effects of alcohol on proteins with those of sodium
      dodecyl sulfate (SDS), we examined the effects of SDS on K3. SDS also induced
      fibrils to form with a maximum at approximately 4 mM, slightly below the critical
      micelle concentration. These results indicate that, with an increase in the
      concentration of hydrophobic cosolvent (TFE, HFIP, or SDS), a delicate balance of
      decreasing hydrophobic interactions and increasing polar interactions (i.e. H
      bonds) in and between peptides leads to the formation of ordered fibrils with a
      bell-shaped concentration dependence.

PMID- 16959265
TI  - Minimalist protein model as a diagnostic tool for misfolding and aggregation.
AB  - We propose a realistic coarse-grained protein model and a technique to "anchor"
      the model to available experimental data. We apply this procedure to characterize
      the effect of multiple mutations on the folding mechanism of protein S6. We show
      that the mutation of a few "gatekeeper" residues triggers significant changes on
      the folding landscape of S6. These results suggest that gatekeeper residues
      control the flexibility of critical regions of S6, that in turn regulates the
      delicate balance between folding and aggregation. Although obtained with a
      minimalist protein model, these results are fully consistent with experimental
      evidence and offer a clue to understand the interplay between folding and
      aggregation in protein S6.

PMID- 16959266
TI  - Complex functionality of gene groups identified from high-throughput data.
AB  - Relating experimental data to biological knowledge is necessary to cope with the
      avalanches of new data emerging from recent developments in high-throughput
      technologies. Automatic functional profiling becomes the de facto standard
      approach for the secondary analysis of high-throughput data. A number of tools
      employing available gene functional annotations have been developed for this
      purpose. However, current annotations are derived mostly from traditional
      analysis of the individual gene function. The complex biological phenomena
      carried out by the concerted activity of many genes often requires the definition
      of new complex functionality (related to a group of genes), which is, in many
      cases, not available in current annotation vocabularies. Functional profiling
      with annotation terms related to the description of individual biological
      functions of a gene may fail to provide reasonable interpretation of biological
      relationships in a set of genes involved in complex biological phenomena. We
      introduce a novel procedure to profile a complex functionality of a gene set.
      Complex functionality is constructed as a combination of available annotation
      terms. By profiling ChIP-chip data from Saccharomyces cerevisiae we demonstrate
      that this technique produces deeper insights into the results of high-throughput
      experiments that are beyond the known facts described in the functional
      classifications.

PMID- 16959267
TI  - Apolipoprotein E gene polymorphism and previous alcohol withdrawal seizures.
AB  - Aim of this study was to investigate the possible association of apolipoprotein E
      (ApoE) gene polymorphism with a history of alcohol withdrawal seizures. We
      included 194 patients with alcohol dependence who were divided into patients with
      (SZ+) and without (SZ-) previous alcohol withdrawal seizures. ApoE genotypes were
      determined using PCR. For statistical analysis we examined the number of ApoE
      alleles (ApoE2: n=36; ApoE3: n=311; ApoE4: n=41). A significant positive
      association with a positive history of withdrawal seizures (SZ+) was found in the
      ApoE3 allele group (Fisher's exact test: p=0.006) while a significant negative
      association was observed in the ApoE2 allele group (Fisher's exact test:
      p=0.029). For the ApoE4 allele group no significant differences were found
      regarding a history of withdrawal seizures. Our findings suggest an association
      between the apolipoprotein E3 gene variant and an elevated risk of alcohol
      withdrawal seizures. These preliminary results must be validated in further
      studies.

PMID- 16959268
TI  - A model for the origin of internal eliminated segments (IESs) and gene
      rearrangement in stichotrichous ciliates.
AB  - A characteristic feature of ciliates (ciliated protozoans) is their nuclear
      dimorphism: the presence of two kinds of functionally different nuclei in the
      same cell--a micronucleus (MIC) and the macronucleus (MAC). In the stichotrichous
      group of ciliates the organization of DNA in the MIC is dramatically different
      from that in the MAC. Genes in the MIC consist of the sequence of segments,
      called MDSs, which are separated by short noncoding pieces of DNA, called IESs.
      Moreover, the order of MDSs in the MIC may be scrambled compared to their order
      in the MAC, and also some MDSs may be inverted with respect to each other. In
      this paper, we consider the evolutionary origin of this bizarre form of MIC
      genes, and in particular we postulate that the insertion of IESs as well as
      possible scramblings/inversions have resulted from a repair of one or more breaks
      in a DNA molecule. We propose a specific repair scheme, and postulate that this
      repair scheme applied to a coiled structure of a DNA molecule that has undergone
      multiple breaks can produce IES insertions and/or scrambled/inverted MIC gene
      patterns. All experimentally demonstrated as well as theoretical MIC gene
      patterns can be produced in this way.

PMID- 16959269
TI  - Modeling of pattern regulation in melanophores.
AB  - Melanosomes, pigment granules in melanophores, play a principal role in
      physiological color adaptation of fish and frog. Melanophores regulate melanosome
      trafficking on cytoskeletal filaments to generate a range of spatiotemporal
      patterns. Here, we present the first comprehensive model of spatiotemporal
      evolution of melanosome patterns. The model encompasses both physical and
      biochemical aspects of melanosome dynamics. It consists of (i) a kinetic
      description of biochemical reactions involved in intracellular signaling, (ii) a
      system of macroscopic reaction-diffusion-convection equations for melanosome
      concentration, and (iii) a set of constitutive relationships for coupling
      transport with the biochemical network. The model relates molecular-level
      regulatory actions to cell-level melanosome distribution, allowing unification of
      existing experimental observations and qualitative hypotheses into an integrated,
      consistent framework. The model reproduces salient features of melanosome
      patterns, both during transient and steady state. It gives useful insights into
      how cells coordinate motor-assisted transport to maintain and adapt spatial
      organization of intracellular organelles. In particular, we calculate the optimal
      transition paths from aggregation to dispersion in fish melanophores. The
      calculations suggest that fish melanophores optimally control intracellular
      signaling to maximize the efficiency of motor-assisted transport during
      dispersion.

PMID- 16959270
TI  - A statistical framework for genome-wide scanning and testing of imprinted
      quantitative trait loci.
AB  - Non-equivalent expression of alleles at a locus results in genomic imprinting. In
      this article, a statistical framework for genome-wide scanning and testing of
      imprinted quantitative trait loci (iQTL) underlying complex traits is developed
      based on experimental crosses of inbred line species in backcross populations.
      The joint likelihood function is composed of four component likelihood functions
      with each of them derived from one of four backcross families. The proposed
      approach models genomic imprinting effect as a probability measure with which one
      can test the degree of imprinting. Simulation results show that the model is
      robust for identifying iQTL with various degree of imprinting ranging from no
      imprinting, partial imprinting to complete imprinting. Under various simulation
      scenarios, the proposed model shows consistent parameter estimation with
      reasonable precision and high power in testing iQTL. When a QTL shows Mendelian
      effect, the proposed model also outperforms traditional Mendelian model.
      Extension to incorporate maternal effect is also given. The developed model,
      built within the maximum likelihood framework and implemented with the EM
      algorithm, provides a quantitative framework for testing and estimating iQTL
      involved in the genetic control of complex traits.

PMID- 16959271
TI  - Combined administration of captopril with an antihypertensive Val-Tyr di-peptide
      to spontaneously hypertensive rats attenuates the blood pressure lowering effect.
AB  - Some di-peptides have been proven to exert an antihypertensive effect in mild
      hypertensive subjects. The aim of this study was to clarify whether combined
      administration of an ACE inhibitor, captopril, with an antihypertensive di
      peptide Val-Tyr (VY) would alter their potent antihypertensive effects in
      spontaneously hypertensive rats (SHRs). Single oral administration of captopril
      (2.5 mg/kg), VY (25 mg/kg), or captopril (2.5 mg/kg)+VY (25 mg/kg) to 18-week-old
      male SHRs was performed. Systolic blood pressure (SBP) was measured up to 9 h,
      and plasma captopril concentrations were determined. A transport study of
      captopril and/or VY across living rat jejunum from SHRs was also performed to
      evaluate the kinetics of absorption. Combined administration of captopril with VY
      failed to lower the BP during the 9-h experiment. A transport study of captopril
      or VY revealed that VY inhibited captopril transport, and vice versa, in a
      competitive manner and exhibited an approximately 1/3-fold lower Ki value for
      captopril compared with that for VY; indicating that both compounds compete for
      the same membrane transport pathway. A 50% decrease in plasma captopril levels by
      combined administration with VY supported that the attenuation of the BP lowering
      effect was due to inhibition of captopril uptake by VY. Consequently, our
      findings suggest that subjects treated with ACE inhibitors for hypertension
      should avoid combined-intake with antihypertensive foods that are rich in small
      peptides due to the competitive inhibition of drug uptake by these peptides.

PMID- 16959272
TI  - Antiangiogenic and antitumor activities of peptide inhibiting the vascular
      endothelial growth factor binding to neuropilin-1.
AB  - Neuropilin-1 (NRP-1), a non-tyrosine kinase receptor of vascular endothelial
      growth factor-165 (VEGF165), was found expressed on endothelial and some tumor
      cells. Since its overexpression is correlated with tumor angiogenesis and
      progression, the targeting of NRP-1 could be a potential anti-cancer strategy. To
      explore this hypothesis, we identified a peptide inhibiting the VEGF165 binding
      to NRP-1 and we tested whether it was able to inhibit tumor growth and
      angiogenesis. To prove the target of peptide action, we assessed its effects on
      binding of radiolabeled VEGF165 to recombinant receptors and to cultured cells
      expressing only VEGFR-2 (KDR) or NRP-1. Antiangiogenic activity of the peptide
      was tested in vitro in tubulogenesis assays and in vivo in nude mice
      xenotransplanted in fat-pad with breast cancer MDA-MB-231 cells. Tumor volumes,
      vascularity and proliferation indices were determined. The selected peptide,
      ATWLPPR, inhibited the VEGF165 binding to NRP-1 but not to tyrosine kinase
      receptors, VEGFR-1 (flt-1) and KDR; nor did it bind to heparin. It diminished the
      VEGF-induced human umbilical vein endothelial cell proliferation and tubular
      formation on Matrigel and in co-culture with fibroblasts. Administration of
      ATWLPPR to nude mice inhibited the growth of MDA-MB-231 xenografts, and reduced
      blood vessel density and endothelial cell area but did not alter the
      proliferation indices of the tumor. In conclusion, ATWLPPR, a previously
      identified KDR-interacting peptide, was shown to inhibit the VEGF165 interactions
      with NRP-1 but not with KDR and to decrease the tumor angiogenesis and growth,
      thus validating, in vivo, NRP-1 as a possible target for antiangiogenic and
      antitumor agents.

PMID- 16959273
TI  - Emodin inhibits TNF alpha-induced MMP-1 expression through suppression of
      activator protein-1 (AP-1).
AB  - Matrix metalloproteinases (MMPs) are the proteases involved in the degradation of
      the extracellular matrix. MMP-1 is thought to be one of the key enzymes acting in
      fibrolysis, a process closely related to tissue remodeling. In this study, we
      found that emodin, an anthraquinone which has been isolated from the rhizome of
      Rheum palmatum, significantly inhibited TNF alpha-induced MMP-1 gene expression
      in a concentration-dependent manner. Therefore, we have attempted to characterize
      the inhibitory mechanism of emodin in TNF alpha-induced MMP-1 expression. Emodin
      was determined to inhibit TNF alpha-induced activation of AP-1 promoter, an
      important nuclear transcription factor in MMP-1 expression. Additionally, we
      detected that emodin suppressed the TNF alpha-induced phosphorylation of two
      mitogen-activated protein kinases, extracellular signal-regulated protein kinase
      and c-Jun N-terminal kinase, but it did not suppress the TNF alpha-induced
      phosphorylation of p38 kinase. In a consistent result, the TNF alpha-induced MMP
      1 expression was inhibited by PD98059 (MEK/ERK inhibitor) and SP600125 (JNK
      inhibitor), but was not inhibited by SB203580, a p38 MAPK inhibitor. Taken
      together, these results show that emodin suppresses TNF alpha-induced MMP-1
      expression through the inhibition of the AP-1 signaling pathway.

PMID- 16959274
TI  - Corosolic acid prevents oxidative stress, inflammation and hypertension in
      SHR/NDmcr-cp rats, a model of metabolic syndrome.
AB  - Corosolic acid (CRA), a constituent of banaba leaves, has been reported to have
      anti-inflammatory and hypoglycemic activities. The aim of this study was to
      determine the effects of CRA on metabolic risk factors including obesity,
      hypertension, hyperinsulinemia, hyperglycemia, and hyperlipidemia together with
      oxidative stress and inflammation, all of which are characteristic of the
      SHR/NDmcr-cp (cp/cp) (SHR-cp) rat, an animal model of metabolic syndrome. Six
      week-old male SHR-cp rats were fed a high fat diet containing 0.072% CRA for 14
      weeks. Treatment with CRA lowered blood pressure, which was elevated in control
      animals, by 10% after 8 weeks, and serum free fatty acids by 21% after 2 weeks.
      CRA treatment resulted in decreases in the levels of the oxidative stress markers
      thiobarbituric acid-reactive substances and 8-hydroxydeoxyguanosine by 27% and
      59%, respectively, after 2 weeks. CRA treatment also reduced the levels of
      myeloperoxidase markers, 3-nitrotyrosine and 3-chlorotyrosine by 38% and 39%,
      respectively, after 10 weeks, and tended to decrease the levels of high
      sensitivity C-reactive protein, a marker of inflammation, after 6 weeks. However,
      CRA had no effect on weight gain or hyperglycemia. These results demonstrate that
      CRA can ameliorate hypertension, abnormal lipid metabolism, and oxidative stress
      as well as the inflammatory state in SHR-cp rats. This implies that CRA can be
      beneficial for preventing atherosclerosis-related diseases that are an increasing
      health care problem worldwide.

PMID- 16959275
TI  - Effects of nicotine exposure during prenatal or perinatal period on cell numbers
      in adult rat hippocampus and cerebellum: a stereology study.
AB  - Smoking during pregnancy poses a potential risk to unborn children. The present
      study examined the long-term effects of early nicotine exposure on the number of
      pyramidal and granule cells in the hippocampus, and Purkinje cells in the
      cerebellar vermis. The loss of neurons is the most severe form of brain injury
      with significant functional implications. In this study, rats were exposed to
      nicotine during either the prenatal (PRE) period or both the prenatal and early
      postnatal (PERI) period. It was hypothesized that nicotine treatment would result
      in long-term decreases in neuronal numbers, and that PERI treatment would be more
      detrimental to these cell populations than the PRE treatment. The results showed
      that neither PRE nor PERI nicotine exposure reduces the numbers of pyramidal,
      granule or Purkinje cells. Neither the regions where these cells reside, nor the
      cell densities were affected by nicotine. Although no significant cell loss was
      observed, the current nicotine exposure regimens may lead to alterations in
      cellular functions or cytoarchitectures. The present results in conjunction with
      previous reports showing significant cell loss from nicotine exposure during the
      brain growth spurt suggest that "patch-like" nicotine exposure during prenatal
      period may alter the sensitivity or the responsiveness of the developing brain to
      the injurious effects of nicotine during the most vulnerable stage of brain
      development - the brain growth spurt. Furthermore, the current stereology cell
      counting results are not in agreement with some reports in the literature, and
      this discrepancy may simply be a function of different cell counting techniques
      used.

PMID- 16959276
TI  - Minisatellite germline mutation rate in the Techa River population.
AB  - Germline mutation at eight minisatellite loci has been studied among the
      irradiated families from the Techa River population and non-exposed families from
      the rural area of the Chelyabinsk and Kurgan Oblasts. The groups were matched by
      ethnicity, parental age, occupation and smoking habit. A statistically
      significant 1.7-fold increase in mutation rate was found in the germline of
      irradiated fathers, whereas maternal germline mutation rate in the exposed
      families was not elevated. Most of the minisatellite loci showed an elevated
      paternal mutation rate in the exposed group, indicating a generalised increase in
      minisatellite germline mutation rate in the Techa River population. These data
      suggest that the elevated minisatellite mutation rate can be attributed to
      radioactive exposure. The spectra of paternal mutation seen in the unexposed and
      exposed families were indistinguishable.

PMID- 16959277
TI  - Event related potentials and the perception of intensity in facial expressions.
AB  - It is well known from everyday experience, that facial expressions of emotions
      can very much vary in intensity, e.g. ranging from mild anger to rage, or from
      uneasiness and mild fear to angst and panic. However, the effect of different
      intensities of facial expressions of emotion on event related potentials has yet
      not been studied. We therefore investigated 16 healthy participants with a gender
      decision task to male and female faces displaying angry, disgusted and fearful
      facial expressions varying in intensity (50%, 100%, 150%). Analysis of ERP data
      showed a significant increase in amplitude of the N170 by intensity, but not by
      type of emotion. The intensity induced negative variation was most pronounced
      between 200 and 600ms at electrodes P9 and P10. For this time segment, there was
      a clear linear relationship between intensity and degree of negative deflection.
      A dipole source localisation of the intensity effect using the difference
      waveform (150% minus 50% intensity) revealed two symmetrically positioned
      generators within the inferior temporo-occipital lobe. An emotion specific effect
      for disgust was further found at temporal electrode sites (FT7 and FT8) at around
      350-400ms. Results are summarised in a two-phase model of emotion recognition,
      suggesting the existence of an initial monitoring process which codes saliency of
      incoming facial information. In a second step, the specific emotional content of
      faces is decoded in emotion specific recognition systems.

PMID- 16959278
TI  - Vestibular integration in human cerebral cortex contributes to spatial remapping.
AB  - The process of visuo-spatial updating is crucial in guiding human behaviour.
      While the parietal cortex has long been considered a principal candidate for
      performing spatial transformations, the exact underlying mechanisms are still
      unclear. In this study, we investigated in a patient with a right occipito
      parietal lesion the ability to update the visual space during vestibularly guided
      saccades. To quantify the possible deficits in visual and vestibular memory
      processes, we studied the subject's performance in two separate memory tasks,
      visual (VIS) and vestibular (VES). In the VIS task, a saccade was elicited from a
      central fixation point to the location of a visual memorized target and in the
      VEST task, the saccade was elicited after whole-body rotation to the starting
      position thus compensating for the rotation. Finally, in an updating task (UPD),
      the subject had to memorize the position of a visual target then after a whole
      body rotation he had to produce a saccade to the remembered visual target
      location in space. Our main findings was a significant hypometria in the final
      eye position of both VEST and UPD saccades induced during rotation to the left
      (contralesional) hemispace as compared to saccades induced after right
      (ipsilesional) rotation. Moreover, these deficits in vestibularly guided saccades
      correlated with deficits in vestibulo-ocular time constant, reflecting disorders
      in the inertial vestibular integration path. We conclude that the occipito
      parietal cortex in man can provide a first stage in visuo-spatial remapping by
      encoding inertial head position signals during gaze orientation.

PMID- 16959279
TI  - Effects of pelvic, pudendal, or hypogastric nerve cuts on Fos induction in the
      rat brain following vaginocervical stimulation.
AB  - In the female rat, genitosensory input is conveyed to the central nervous system
      predominantly through the pelvic, pudendal, and hypogastric nerves. The present
      study examined the relative contribution of those three nerves in the expression
      of Fos immunoreactivity within brain regions previously shown to be activated by
      vaginocervical stimulation (VCS). Bilateral transection of those nerves, or sham
      neurectomy, was conducted in separate groups of ovariectomized, sexually
      experienced females. After recovery, females were primed with estrogen and
      progesterone and given either 50 manual VCSs with a lubricated glass rod over the
      course of 1 h. VCS increased the number of neurons expressing Fos
      immunoreactivity in the medial preoptic area, lateral septum, bed nucleus of the
      stria terminalis, ventromedial hypothalamus, and medial amygdala of sham
      neurectomized females. Transection of the pelvic nerve reduced Fos
      immunoreactivity in the medial preoptic area, bed nucleus of the stria
      terminalis, ventromedial hypothalamus, and medial amygdala, whereas transection
      of the pudendal nerve had no effect. In contrast, transection of the hypogastric
      nerve increased Fos immunoreactivity in the medial preoptic area and lateral
      septum, whereas transaction of the pelvic nerve increased Fos immunoreactivity in
      the lateral septum, following VCS. All females given VCS, except those with
      pelvic neurectomy, displayed a characteristic immobility during each application.
      These data confirm that the pelvic nerve is largely responsible for the neural
      and behavioral effects of VCS, and support a separate function for the
      hypogastric nerve.

PMID- 16959280
TI  - Scent-marking and sexual activity may reflect social hierarchy among group-living
      male Mongolian gerbils (Meriones unguiculatus).
AB  - Social hierarchy plays an important role in the lives of gregarious species. We
      investigated how social hierarchy between male Mongolian gerbils (Meriones
      unguiculatus) housed together before sexual maturity affected their scent-marking
      behavior, endocrine status and physical traits as adults. The social rank between
      paired males was assessed based on sexual activity in adulthood at 18 and 20
      weeks of age. In most cases, the male that showed higher sexual activity at 18
      weeks also exhibited greater sexual performance at 20 weeks, suggesting a
      precedence relationship between paired males regarding reproductive opportunity.
      Sexually active males scent-marked more often than their cage mate, particularly
      after a sexual experience. No significant differences in physical traits (e.g.,
      the weight of the ventral gland, testes and adrenal glands) or endocrine status
      (e.g., fecal testosterone and corticosterone levels) were found between the two
      males. These findings suggest that social rank between familiar males formed
      during cohabitation, and rank was closely correlated with scent-marking activity,
      but not with endocrine status.

PMID- 16959281
TI  - Synthetic aperture ultrasound imaging.
AB  - The paper describes the use of synthetic aperture (SA) imaging in medical
      ultrasound. SA imaging is a radical break with today's commercial systems, where
      the image is acquired sequentially one image line at a time. This puts a strict
      limit on the frame rate and the possibility of acquiring a sufficient amount of
      data for high precision flow estimation. These constrictions can be lifted by
      employing SA imaging. Here data is acquired simultaneously from all directions
      over a number of emissions, and the full image can be reconstructed from this
      data. The paper demonstrates the many benefits of SA imaging. Due to the complete
      data set, it is possible to have both dynamic transmit and receive focusing to
      improve contrast and resolution. It is also possible to improve penetration depth
      by employing codes during ultrasound transmission. Data sets for vector flow
      imaging can be acquired using short imaging sequences, whereby both the correct
      velocity magnitude and angle can be estimated. A number of examples of both
      phantom and in vivo SA images will be presented measured by the experimental
      ultrasound scanner RASMUS to demonstrate the many benefits of SA imaging.

PMID- 16959282
TI  - Characterization of human metapneumovirus infection of myeloid dendritic cells.
AB  - Recent in vivo studies suggest that hMPV is a poor inducer of inflammatory
      cytokines and that clinical symptoms may not be related to immune-mediated
      pathogenesis as it has been proposed for respiratory syncytial virus (RSV) and
      human parainfluenza 3 (HPF3). Dendritic cells (DCs) are specialized antigen
      presenting cells, and very effective at inducing specific CTLs after encountering
      invading viruses. Interactions of hMPV with DCs have not been characterized. We
      hypothesized that the relatively mild inflammatory responses observed in vivo
      after hMPV infection might be at least in part due to hMPV's poor ability to
      stimulate and activate DCs. hMPV actively infected immature monocyte-derived
      CD11c+/HLA-DR+ DCs. However, in contrast to RSV or HPF3, hMPV caused no gross
      cytopathic effects such as syncytia, lytic infection, or massive apoptosis. DCs
      exposed to hMPV show no cytopathic effects under tissue culture conditions
      permissive for viral replication. The surface maturation markers CD83 and CD86
      were not significantly up-regulated in infected DCs as compared to uninfected
      controls, while expression of CD80 appeared increased. Stimulation of hMPV
      infected DCs with LPS resulted in the enhanced expression of all these surface
      markers indicating that hMPV is not generally suppressing DC maturation. Overall,
      cytokine expression remained low. These results indicate that hMPV does not
      induce effective DC maturation in vitro and suggest that the weak stimulation of
      DCs may account for the overall low immunogenicity of this virus observed in
      vivo.

PMID- 16959283
TI  - Structure-based mutagenesis of the integrase-LEDGF/p75 interface uncouples a
      strict correlation between in vitro protein binding and HIV-1 fitness.
AB  - LEDGF/p75 binding-defective IN mutant viruses were previously characterized as
      replication-defective, yet RNAi did not reveal an essential role for the host
      factor in HIV-1 replication. Correlative analyses of protein binding and viral
      fitness were expanded here by targeting 12 residues at the IN-LEDGF/p75 binding
      interface. Whereas many of the resultant viruses were defective, the majority of
      the INs displayed wild-type in vitro integration activities. Though an overall
      trend of parallel loss of LEDGF/p75 binding and HIV-1 infectivity was observed, a
      strict correlation was not. His-tagged IN(A128Q), derived from a phenotypically
      wild-type virus, failed to pull-down LEDGF/p75, but IN(A128Q) was effectively
      recovered in a reciprocal GST pull-down assay. Under these conditions, IN(H171A),
      also derived from a phenotypically wild-type virus, interacted less efficiently
      than a previously described interaction-defective mutant, IN(Q168A). Thus, the
      relative affinity of the in vitro IN-LEDGF/p75 interaction is not a universal
      predictor of IN mutant viral fitness.

PMID- 16959284
TI  - Complexities in human herpesvirus-6A and -6B binding to host cells.
AB  - Human herpesvirus-6A and -6B uses the cellular receptor CD46 for fusion and
      infection of the host cell. The viral glycoprotein complex gH-gL from HHV-6A
      binds to the short consensus repeat 2 and 3 in CD46. Although all the major
      isoforms of CD46 bind the virus, certain isoforms may have higher affinity than
      others for the virus. Within recent years, elucidation of the viral complex has
      identified additional HHV-6A and -6B specific glycoproteins. Thus, gH-gL
      associates with a gQ1-gQ2 dimer to form a heterotetrameric complex. In addition,
      a novel complex consisting of gH-gL-gO has been described that does not bind
      CD46. Accumulating evidence suggests that an additional HHV-6A and -6B receptor
      exists. The previous simple picture of HHV-6A/B-host cell contact therefore
      includes more layers of complexities on both the viral and the host cell side of
      the interaction.

PMID- 16959285
TI  - Mutation of the Myxoma virus SERP2 P1-site to prevent proteinase inhibition
      causes apoptosis in cultured RK-13 cells and attenuates disease in rabbits, but
      mutation to alter specificity causes apoptosis without reducing virulence.
AB  - Myxoma virus (MYX) prevents apoptosis in RK-13 cells and forms thick dermal
      lesions with 100% mortality in rabbits. MYX encodes the virulence factor SERP2, a
      serine proteinase inhibitor (serpin). SERP2 was mutated to evaluate SERP2
      function during MYX infection. MYXDeltaSERP2::lacZ (deleted for SERP2) did not
      inhibit apoptosis in RK-13 cells; infected rabbits had thin dermal lesions and
      <10% mortality. MYX-SERP2-D294A, a P1-site aspartate to alanine mutant,
      inactivated the serpin; infection was indistinguishable from MYXDeltaSERP2::lacZ.
      SERP2-D294E prevented inhibition of caspase-8, caspase-10 and granzyme-B; and MYX
      SERP2-D294E failed to block apoptosis in RK-13 cells, but was fully virulent in
      rabbits. MYXDeltaSERP2::crmA expressed crmA instead of SERP2 and inhibited
      apoptosis in cell culture, but caused thin lesions and only 70% mortality in
      rabbits, hence crmA cannot fully substitute for SERP2. Control of apoptosis in
      culture does not correlate with virulence in rabbits. Virulence may instead
      depend on inhibition of proinflammatory proteinases by SERP2.

PMID- 16959287
TI  - Synergism of a DNA and an RNA virus: enhanced tissue infiltration of the
      begomovirus Abutilon mosaic virus (AbMV) mediated by Cucumber mosaic virus (CMV).
AB  - Replication of the begomovirus Abutilon mosaic virus (AbMV) is restricted to
      phloem nuclei, generating moderate levels of virus DNA. Co-infection with
      Cucumber mosaic virus (CMV) evidently increased AbMV titers in Nicotiana
      benthamiana, tobacco, and tomato, resulting in synergistic symptom enhancement.
      In situ hybridization revealed that in double-infected leaves an increased number
      of nuclei contained elevated amounts of AbMV. Additionally, the begomoviral
      phloem-limitation was broken. Whereas CMV 3a movement protein-expressing tobacco
      plants did not exert any similar influence, the presence of CMV 2b silencing
      suppressor protein lead to enhanced AbMV titers and numbers of infected vascular
      cells. The findings prove that AbMV can replicate in nonvascular cells and
      represent the first report on a true synergism of an RNA/ssDNA virus combination
      in plants, in which CMV 2b protein plays a role. They indicate considerable
      consequences of mixed infections between begomo- and cucumoviruses on virus
      epidemiology and agriculture.

PMID- 16959286
TI  - Adeno-associated virus interactions with B23/Nucleophosmin: identification of sub
      nucleolar virion regions.
AB  - Adeno-associated virus (AAV) is a human parvovirus that normally requires a
      helper virus such as adenovirus (Ad) for replication. The four replication
      proteins (Rep78, 68, 52 and 40) encoded by AAV are pleiotropic effectors of virus
      integration, replication, transcription and virion assembly. Using Rep68 column
      chromatography and mass spectrometry, we have identified the nucleolar,
      B23/Nucleophosmin (NPM) protein as an Rep-interacting partner. Rep-NPM
      interactions were verified by co-immunofluorescence and chemical cross-linking
      studies. We have found that there is demonstrable, but limited co-localization
      between Rep and NPM in co-infected cells. In contrast, there was significant co
      localization between NPM and AAV Cap proteins. In vitro experiments using
      purified MBPRep78 and NPM show that NPM stimulates MBPRep78 interactions with the
      AAV ITR as well as endonuclease activity. These studies suggest that NPM plays a
      role in AAV amplification affecting Rep function and virion assembly.

PMID- 16959288
TI  - The human RNA polymerase II interacts with the terminal stem-loop regions of the
      hepatitis delta virus RNA genome.
AB  - The hepatitis delta virus (HDV) is an RNA virus that depends on DNA-dependent RNA
      polymerase (RNAP) for its transcription and replication. While it is generally
      accepted that RNAP II is involved in HDV replication, its interaction with HDV
      RNA requires confirmation. A monoclonal antibody specific to the carboxy terminal
      domain of the largest subunit of RNAP II was used to establish the association of
      RNAP II with both polarities of HDV RNA in HeLa cells. Co-immunoprecipitations
      using HeLa nuclear extract revealed that RNAP II interacts with HDV-derived RNAs
      at sites located within the terminal stem-loop domains of both polarities of HDV
      RNA. Analysis of these regions revealed a strong selection to maintain a rod-like
      conformation and demonstrated several conserved features. These results provide
      the first direct evidence of an association between human RNAP II and HDV RNA and
      suggest two transcription start sites on both polarities of HDV RNA.

PMID- 16959289
TI  - Elimination of resin acids by advanced oxidation processes and their impact on
      subsequent biodegradation.
AB  - Wood pulping and paper production generate a considerable amount of wastewater,
      containing many pollutants among them resin and fatty acids. Resin acids
      contribute substantially to effluent toxicity and were identified to be
      detrimental to microorganisms of activated sludge and in particular to bacteria
      in anaerobic wastewater treatment system and other forms of aquatic life. The
      objective of the present study was to check the applicability of the ozone and
      advanced oxidation processes (AOPs) to eliminate resin acids from aqueous
      solutions and to determine the ozone dose required. Furthermore, an investigation
      of the influence of the oxidation methods on subsequent biological destruction of
      the byproducts was performed. Aqueous solution of the resin acids: abietic,
      dehydroabietic and isopimaric acids with different initial composition were
      subjected to ozonation or AOP processes at different ozone doses. After ozonation
      or advanced oxidation pretreatment the model solutions were biodegraded in
      aerated vessels containing activated sludge. During ozonation of the resin acids
      aqueous solutions the resin acids were almost eliminated, however the reduction
      of chemical oxygen demand (COD) was rather low. The ozone dose required to obtain
      reduction of resin acids >90% was in the range of 0.1-0.7mgO(3)/mgCOD, depending
      on the composition and concentration of model solutions. The toxicity of ozonated
      resin acids solutions decreased with increasing applied ozone dose up to about
      0.3-0.5mgO(3)/mgCOD, thereafter increased. Ozonation and other AOP processes did
      not increase the rate of biodegradation of resin acids model solutions in aerated
      activated sludge systems compared to not pretreated solutions.

PMID- 16959290
TI  - Batch foam separation of a soluble protein.
AB  - Removal of protein dissolved in water by batch foam separation was conducted with
      using ovalbumin (OA) as a model protein in the light of wastewater treatment
      reducing organic loading. The removal efficiency had a maximum value near the
      i.e.p. of OA (pH 4.6); thus, most experiments were conducted at pH 4.6. Typical
      experimental conditions; superficial gas velocity, U(g): 1.97 x 10(-2)-5.37 x 10(
      2)cm/s; initial bulk concentration of OA, C(i): ca. 0.05-0.25 g/L; liquid volume,
      V: 600 cm(3). A model estimating bulk concentration profile was proposed by
      taking into account a mass balance of the present system. The model predicted
      that OA could be removed perfectly, however, was not all removed experimentally.
      The residual OA concentration of the bulk liquid within the column reached
      plateau value, which correspond to ca. 18% of the initial OA concentration. The
      plateau value of the bulk concentration was attained for ca. 100-500 min with
      U(g)=1.97 x 10(-2)-5.37 x 10(-2)cm/s. Foaming ability test revealed that the
      foaming limit concentration of OA at pH 4.6 was 9.72 x 10(-3)g/L. These results
      suggested that OA molecules could be damaged by interaction of bubble surface in
      the dispersed phase, since there were the residual OA concentrations over the
      limit concentration. To take account of this phenomena and correct the model,
      average surface density, X(d), which should convert protein molecule into the
      denatured protein molecule, was introduced. The corrected model could explain
      well the time profile of OA bulk concentration.

PMID- 16959291
TI  - Comparing the response of biochemical indicators (biomarkers) and biological
      indices to diagnose the ecological impact of an oil spillage in a Mediterranean
      river (NE Catalunya, Spain).
AB  - Three biomarkers of hydrocarbon exposure, liver 7-ethoxyresourfin-O-deethylase
      activity (EROD), fluorescent hydrocarbon compounds (FACs) in bilis, and the liver
      antioxidant enzyme catalase (CAT) were examined in the autochthonous fish species
      Barbus meridionalis collected in the river Fluvia (NE Catalunya, Spain) after an
      oil spillage. Four different locations were sampled, including the impacted site,
      upstream and downstream sites and a reference site. Biomarker responses were
      compared with diatom and macroinvertebrate community assemblage metrics (Specific
      Pollution Sensitivity index - IPS, and Iberian Biological Monitoring Working
      Party - IBMWP, respectively). Chemical analyses denoted that polycyclic aromatic
      hydrocarbon levels in sediment were much higher at the impacted site than in
      downstream reaches. Four fold increase of EROD activity together with increased
      levels of biliary FACs in barbs collected at the spilled site indicated exposure
      of inhabiting fish to the oil. Additionally, CAT activity was significantly
      depressed (four fold) when compared to other stations, thus suggesting that fish
      collected from the impacted sites could be more susceptible to suffer oxidative
      stress. Biological indices (particularly that of the diatom community IPS) showed
      slight significant effects between control and impacted sites, indicating that
      more tolerant taxa were favoured because of the oil spillage. These results
      support the need to include biochemical responses measured in local species in
      monitoring programmes aimed to diagnose specific pollution effects in stressed
      river ecosystems.

PMID- 16959292
TI  - Monobromo and higher brominated congeners of the marine halogenated natural
      product 2,3,3',4,4',5,5'-heptachloro-1'-methyl-1,2'-bipyrrole (Q1).
AB  - The marine halogenated natural product 2,3,3',4,4',5,5'-heptachloro-1'-methyl
      1,2'-bipyrrole (Q1) is widely distributed in the environment. In this study, we
      screened samples which have previously been found to contain remarkably high
      residues of Q1 (blubber of marine mammals from Australia, samples from
      Antarctica, human milk from the Faroe Island) for the additional presence of
      mixed chlorinated and brominated congeners. Using GC/ECNI-MS, all samples tested
      were positive and many contained four out of five possible bromohexachloro
      congeners (BrCl6-MBPs), five out of 14 possible dibromopentachloro congeners
      (Br2Cl5-MBPs), five of 21 possible tribromotetrachloro-congeners (Br3Cl4-MBPs),
      as well as several higher brominated congeners. About 20 heptahalo congeners of
      Q1 are described for the first time in the scientific literature. Isomers eluted
      within about one minute, respectively. Hence it is possible, that the peak
      clusters identified may be composed of more, co-eluting congeners. Similarities
      in the GC/ECNI-MS mass spectra with polychlorinated biphenyls (PCBs) were
      addressed. We also suggest an acronym system similar to that in use for
      polychlorinated biphenyls that may simplify the use of this substance class in
      scientific papers. In the samples from Australia, BrCl6-MBPs and Br2Cl5-MBPs
      amounted for 7-27.5% and 0.4-4.2% of Q1, respectively whereas Br3Cl4-MBPs and
      higher brominated MBPs were found in the range of <1% of Q1 or less.

PMID- 16959293
TI  - Biodegradation of US premanufacture notice chemicals in OECD tests.
AB  - Biodegradation testing of commercial chemicals other than pesticides is generally
      performed using test guidelines of the Organization for Economic Cooperation and
      Development (OECD). We used test data submitted with US Premanufacture
      Notifications (PMNs) received from 1995 through 2005 to study performance of OECD
      biodegradation tests, as well as the overall testing strategy and guidance. Among
      the findings are that (1) ready biodegradation (RB) tests gave fairly consistent
      results relative to the pass/fail outcome, but not necessarily percent
      degradation; (2) the Zahn-Wellens test worked well in providing a quick measure
      of sorption potential, but aside from this, provided little useful information
      for the investigated chemicals beyond what was already available from RB tests;
      (3) the SCAS test sometimes gives lower % removal than continuous-feed simulation
      tests like OECD 303A; and (4) OECD 306 (marine biodegradation test) appeared less
      conservative than ordinary RB tests. Overall, the PMN data lend support to new
      OECD guidance that endorses the primary role of RB tests, but emphasizes
      simulation rather than inherent biodegradation tests as the next step.

PMID- 16959294
TI  - Modeling the impact of direct phototransformation on predicted environmental
      concentrations (PECs) of propranolol hydrochloride in UK and US rivers.
AB  - There is currently uncertainty on the persistence of active pharmaceutical
      ingredients (APIs) and on their depletion mechanisms in natural surface waters
      such as rivers, and hence predictions of their fate are often poor. In this
      study, a beta-adrenergic receptor, propranolol hydrochloride, was selected as a
      model API to explore the relative significance of direct phototransformation as a
      potential removal process of hydrophilic APIs in rivers. Phototransformation
      kinetics of propranolol was measured under simulated solar irradiation in the
      laboratory, which were then converted to the kinetics applicable in UK and US
      rivers. The effects of light intensity, light penetration, river size and flow
      were examined. The extrapolated phototransformation half-lives were applied in
      the river catchment models of GREAT-ER and PhATE. Results demonstrated that
      direct phototransformation significantly reduced the predicted environmental
      concentrations of propranolol in the water phase. Predicted reductions of mean
      concentrations in the River Aire (UK) were 27% in summer and 3% in winter; and
      for the US rivers simulated, reductions were 28-68% in summer and 11-41% in
      winter. The highest reductions were predicted for long rivers with low turbidity
      and low flow conditions.

PMID- 16959295
TI  - A chronic bioassay with the estuarine amphipod Corophium volutator: test method
      description and confounding factors.
AB  - Methods of conducting a chronic sediment toxicity test with the estuarine
      amphipod Corophium volutator are described. They consist of a 49-day exposure,
      after which mortality, growth and reproduction are determined. Pilot experiments
      were used to optimize test design parameters such as temperature, duration,
      feeding and refreshing regimes, and effects of indigenous organisms. By way of
      further validation, the present study focused on the effects of four different
      parameters: oxygen saturation, salinity, ammonium and nitrite. These confounding
      factors might play an important role especially if the test is used for risk
      assessment of field-contaminated sediments. It is concluded that the present
      experimental design is well suited for chronic sediment exposures with C.
      volutator. The test can be performed at a broad range of salinity values,
      provided that controls are performed at the same salinity. Results further
      demonstrate that with the endpoints growth and reproduction this chronic test
      procedure is a factor 7-18 more sensitive to ammonium and nitrate than the
      standardized acute bioassay (endpoint mortality).

PMID- 16959296
TI  - Tetracycline as a selector for resistant bacteria in activated sludge.
AB  - Tetracycline, one of the most widely used antibiotics, is excreted into
      wastewater after consumption by humans and animals. The focus of this research
      was to evaluate the fate of tetracycline resistant bacteria in the activated
      sludge process as a function of tetracycline loading. The studies were conducted
      with aerobic biological sequencing batch reactors (SBRs). When comparing 250
      microgl(-1) tetracycline fed SBRs with parallel SBRs having a background influent
      wastewater tetracycline concentration of approximately 1 microgl(-1),
      tetracycline fed reactors were found to have increased concentrations and
      production rates of tetracycline resistant bacteria, higher net growth rates of
      resistant bacteria, and higher percentages of tetracycline resistant bacteria,
      which were amplified by increase in organic loading and growth rates.

PMID- 16959297
TI  - Biochemical responses of the marine mussel Mytilus galloprovincialis to
      petrochemical environmental contamination along the North-western coast of
      Portugal.
AB  - Following the development of urban and industrial centres petrochemical products
      have become a widespread class of contaminants. The aim of this study was to
      investigate the effects of petrochemical contamination in wild populations of
      mussels (Mytilus galloprovincialis) along the NW Atlantic coast of Portugal by
      applying antioxidant and energetic metabolism parameters as biomarkers. For that,
      mussels were collected at five sampling sites presenting different petrochemical
      contamination levels. To evaluate the mussels' antioxidant status, enzymatic
      activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione
      reductase, glutathione S-transferases, as well as glutathione redox status were
      evaluated in gills and digestive glands of mussels collected from the selected
      sites. Lipid peroxidation was determined in the same tissues to quantify cellular
      oxidative damage. Furthermore, to investigate how energetic processes may respond
      to these contaminants, the activity of NADP(+)-dependent isocitrate dehydrogenase
      was determined in mussels' digestive glands, and octopine dehydrogenase was
      determined in mussels' posterior adductor muscle. Furthermore, the concentrations
      of aliphatic hydrocarbons, unresolved complex mixture and polycyclic aromatic
      hydrocarbons (PAHs) were quantified in mussels' tissue, and abiotic parameters
      were quantified in water samples collected at each site. Several biomarkers
      showed statistically significant differences among sampling sites. The redundancy
      analysis (RDA) used to perform the integrated analysis of the data showed a clear
      separation of the sampling sites in three different assemblages, which are in
      agreement with the PAHs levels found in mussels tissues. In addition, the RDA
      indicated that some of the selected biomarkers may be influenced by abiotic
      parameters (e.g. salinity, pH, nitrates and ammonia). The approach selected for
      this study seems to be suitable for monitoring petrochemical contamination.

PMID- 16959298
TI  - Speed modulation in hylobatid bipedalism: a kinematic analysis.
AB  - Gibbons are highly arboreal apes, and it is expected that their bipedal
      locomotion will show some particularities related to the arboreal environment.
      Previous research has shown that, during hylobatid bipedalism, unsupported phases
      are rare and stride frequencies are relatively low. This study confirms previous
      findings, and we suggest that low stride frequencies and the absence of
      unsupported phases are ways to reduce disadvantageous branch oscillations during
      arboreal travel. Despite these restrictions, gibbons are able to locomote at a
      wide range of speeds, implying that they likely exploit other mechanisms to
      modulate their locomotor speed. To investigate this possibility, we collected
      video images of a large number of spontaneous bipedal bouts of four untrained
      white-handed gibbons by using an instrumented walkway with four synchronized
      cameras. These video images were digitized to obtain a quantification of the 3D
      kinematics of hylobatid bipedalism. We defined a large number of spatiotemporal
      and kinematic gait variables, and the relationship between these gait variables
      and (dimensionless) speed was statistically tested. It was found that gibbons
      mainly increase stride length to increase their locomotor speed; the main speed
      modulating mechanisms are hip and ankle excursion and coupled knee and ankle
      extension at toe-off. Although aerial phases are rare, gibbons generally adopt a
      bipedal bouncing gait at most speeds and a clear-cut gait transition, as seen in
      human locomotion, is absent. Comparison with human and bonobo bipedalism showed
      that the variability of the 3D joint angles of the hind limb are comparable
      during human and gibbon bipedalism, and much lower than during bonobo bipedalism.
      The low variability found in gibbons might be related to constraints imposed by
      the arboreal environment. These arboreal constraints clearly affect the bipedal
      gait characteristics of gibbons, but do not constrain the ability to adopt a
      bipedal bouncing gait during terrestrial locomotion.

PMID- 16959299
TI  - Archaic and modern human distal humeral morphology.
AB  - The morphology of the proximal ulna has been shown to effectively differentiate
      archaic or premodern humans (such as Homo heidelbergensis and H.
      neanderthalensis) from modern humans (H. sapiens). Accordingly, the morphology of
      adjacent, articulating elements should be able to distinguish these two broad
      groups as well. Here we test the taxonomic utility of another portion of the
      elbow, the distal humerus, as a discriminator of archaic and modern humans.
      Principal components analysis was employed on a suite of log-raw and log-shape
      distal humeral measures to examine differences between Neandertal and modern
      human distal humeri. In addition, the morphological affinities of Broken Hill
      (Kabwe) E.898, an archaic human distal humeral fragment from the middle
      Pleistocene of Zambia, and five Pliocene and early Pleistocene australopith
      humeri were assessed. The morphometric analyses effectively differentiated the
      Neandertals from the other groups, while the Broken Hill humerus appears
      morphologically similar to modern human distal humeri. Thus, an archaic/modern
      human dichotomy-as previously reported for proximal ulnar morphology-is not
      supported with respect to distal humeral morphology. Relative to australopiths
      and modern humans, Neandertal humeri are characterized by large olecranon fossae
      and small distodorsal medial and lateral pillars. The seeming disparity in
      morphological affinities of proximal ulnae (in which all archaic human groups
      appear distinct from modern humans) and distal humeri (in which Neandertals
      appear distinct from modern humans, but other archaic humans do not) is probably
      indicative of a highly variable, possibly transitional population of which our
      knowledge is hampered by sample-size limitations imposed by the scarcity of
      middle-to-late Pleistocene premodern human fossils outside of Europe.

PMID- 16959300
TI  - Selenium content in selected foods from the Greek market and estimation of the
      daily intake.
AB  - The total selenium content of foods purchased from the North West part of Greece
      was determined using hydride generation atomic fluorescence spectroscopy. The
      results of this study were within the range from other countries. The overall
      mean average of selenium concentration of the foods examined, in decreasing
      order, was found in sesame seeds (783.1 ng g(-1)), fish (246 ng g(-1)), legumes
      (162.5 ng g(-1)), eggs (123 ng g(-1)), bread (91.9 ng g(-1)), meat (71.7 ng g(
      1)), cheese (69.8 ng g(-1)), yoghurt (23.6 ng g(-1)), nuts (19.6 ng g(-1)), milk
      (15.4 ng g(-1)), vegetables (6.5 ng g(-1)) and fruits (3.4 ng g(-1)). Considering
      the average daily individual consumption of these foods by Greeks, the average
      daily dietary intake of selenium supplied by this source is 39.3 microg per
      capita.

PMID- 16959301
TI  - Abandoned Mid-Canada Radar Line sites in the Western James region of Northern
      Ontario, Canada: a source of organochlorines for First Nations people?
AB  - The potential exists for human exposure to polychlorinated biphenyls (PCBs) and
      other contaminants originating from abandoned Mid-Canada Radar Line (MCRL) sites
      in sub-arctic Canada. We examined patterns of differences with respect to body
      burden of organochlorines (lipid-adjusted) between residents of the Ontario First
      Nations of Fort Albany (the site of MCRL Site 050) and Kashechewan (no radar
      base) and Hamilton (an industrial, southern Ontario community) to assess whether
      the presence of Site 050 influenced organochlorine body burden with respect to
      the people of Fort Albany. PCBs (Aroclor 1260 and summation operator14 PCBs
      congeners [CBs]) and DDE in the plasma of Fort Albany and Kashechewan subjects
      were elevated relative to Hamilton participants. PCB and DDE-plasma levels in
      First Nation women were of comparable magnitude to those reported for Inuit women
      living in the west/central Northwest Territories. Significantly lower DDE/DDT
      ratios observed for Fort Albany indicates exposure to higher levels of DDT
      compared to Kashechewan. The probable source of DDT exposure for Fort Albany
      people is the DDT-contaminated soil surrounding buildings of Site 050. The
      results of the correspondence analysis (CA) indicated that people from Hamilton
      had relatively higher pesticides and lower CB body burdens, while people from
      Fort Albany and Kashechewan exhibited relatively higher CBs and lower pesticide
      levels (CA-1). The separation of Fort Albany and Kashechewan from Hamilton was
      also clear using questionnaire data (i.e., plotting dietary principal component
      [PC]-1 scores against PC-2); PC-1 was correlated with the consumption of a
      traditional diet. Separation of Kashechewan and Albany residents occurred because
      the people of Kashechewan ate more traditional meats and consumed shorebirds.
      Only one significant relationship was found between PC analysis and contaminant
      loadings; PC-1 versus CA-3 for Kashechewan. The presence of Site 050 on Anderson
      Island appears to have influenced organochlorine body burden of the people of
      Fort Albany. ANCOVA results revealed that it was not activity on Anderson Island
      that was important, but activity on Site 050 was the influential variable. When
      these results are considered with the DDE/DDT ratio data and the CB 187 results
      (Fort Albany and Kashechewan residents differed significantly), the findings are
      suggestive that Site 050 did influence organochlorine body burden of people from
      Fort Albany.

PMID- 16959302
TI  - Epidemiological prenatal ultrasound studies.
AB  - Epidemiological studies have indicated no association between diagnostic
      ultrasound exposure during pregnancy and childhood malignancies. Diagnostic
      ultrasound imaging does not seem to influence birth weight, whereas frequent
      Doppler ultrasound was associated with reduced birth weight in one study. Most
      experts do not believe that ultrasound exposure during pregnancy is associated
      with reduced birth weight. There are no confirmed statistically significant
      associations between ultrasound and dyslexia and neurological development during
      childhood. However, two randomised controlled trials and two cohort studies have
      been unable to rule out a possible association between ultrasound and left
      handedness among males.

PMID- 16959303
TI  - Ultrasound, microbubbles and the blood-brain barrier.
AB  - The blood-brain barrier (BBB) is a specialized system of capillary endothelial
      cells that protects the brain from harmful substances in the blood stream, while
      supplying the brain with the required nutrients for proper function. The BBB
      controls transport through both tight junctions and metabolic barriers and is
      often a rate-limiting factor in determining permeation of therapeutic drugs into
      the brain. It is a significant obstacle for delivery of both small molecules and
      macromolecular agents. Although many drugs could be potentially used to treat
      brain disease, there has been no method that allows non-invasive-targeted
      delivery through the BBB. Recently, promising studies indicate that ultrasound
      can be used to locally deliver a drug or gene to a specific region of interest in
      the brain. If microbubbles are combined with ultrasound exposure, the effects of
      ultrasound can be focused upon the vasculature to reduce the acoustic intensity
      needed to produce BBB opening. Several avenues of transcapillary passage after
      ultrasound sonication have been identified including transcytosis, passage
      through endothelial cell cytoplasmic openings, opening of tight junctions and
      free passage through injured endothelium. This article reviews the topic of
      transient disruption of the BBB with ultrasound and microbubbles and addresses
      related safety issues. It also discusses possible roles of the BBB in brain
      disease and potential interactions with ultrasound and microbubbles in such
      disease states.

PMID- 16959304
TI  - Nadroparine activated fibrinolysis and improvement of glomerular filtration rate
      in patients with FIGO IIB-IIIB cervical cancer treated with radiochemotherapy.
AB  - OBJECTIVES: (1) Evaluation of the influence of hemostatic disorders on renal
      function in patients with FIGO stage IIB-IIIB cervical cancer treated with
      radiochemotherapy. (2) Identifying methods of improving renal function in this
      patients group. METHODS: Treatment design assumes the administration of a total
      radiation dose of 46-65 Gy and, additionally, cisplatin 40 mg/m2 every 7 days in
      patients with normal plasma creatinine level. Renal function was assessed with
      the aid of dynamic scintigraphy with glomerular filtration rate (GFR) evaluation.
      Analysis of serum hemostatic system covered D-dimers, PAP, PAI-1, tPA, FDP, F1+2
      and TAT. The same hemostatic parameters were also evaluated in urine. The
      patients were divided into two groups: the study group - i.e. patients with
      affected GFR and the control group - with normal GFR. Half of study group
      patients, throughout the entire treatment, receive nadroparine 2850 units aXa/0.3
      ml every 24 h during and 6 weeks after the treatment. RESULTS: There are
      significant decreases of GFR in control (median -9.7%) and study group without
      nadroparine (median -9.9%) and increase in the GFR (median 22.3%) in study group
      with nadroparine (p=0.0001). Plasma and urine hemostatic parameter analysis
      showed activation of fibrinolysis in patients treated with nadroparine and
      fibrinolysis inhibition in remaining groups. CONCLUSIONS: (1) Inhibition of
      fibrinolysis may cause subclinical renal insufficiency in patients with advanced
      cervical cancer. (2) Insufficiency increases after the end of radiochemotherapy
      in patients, as well with normal GFR as, with primary decreased GFR. (3)
      Application of nadroparine causes fibrinolysis activation, and increase in the
      GFR.

PMID- 16959306
TI  - Comparison of computer-assisted and manual screening of cervical cytology.
AB  - OBJECTIVE: The Pap smear, introduced over 50 years ago, has significantly
      contributed to the reduction of mortality due to cervical cancer. The shortage of
      skilled cytotechnologists to screen and diagnose Pap slides has always been a
      concern, thus driving the goal to develop an automated system. This study
      evaluated the diagnostic performance of an automated computer imaging system for
      routine cervical cancer screening in a high-volume independent laboratory.
      METHODS: Validation and training were conducted upon installation of the computer
      imaging system. Following validation, data were evaluated comparing cytologic
      detection rates of a six-month cohort of slides screened with computer imaging
      assistance versus a historic control of manually screened slides. RESULTS: For
      each cytologic abnormal category, the Imager-assisted detection rates were
      significantly greater than the manually screened historic cohort. The Imager
      increased the detection of HSIL+ by 38% and LSIL by 46% compared to manual
      screening. There was an increase in the rate of ASC in the Imager cohort (6.5%)
      compared to manual screening (4.1%), however, the ASC rate decreased during the
      time of the study period suggesting learning affect. CONCLUSIONS: The results
      indicate that computer-imaging-assisted screening significantly increased the
      cytologic detection of cervical abnormalities compared to manual screening. The
      initial increase in ASC rates is partially due to a new stain protocol that may
      be corrected with additional experience. The implementation of the Imager,
      however, did not adversely affect the ASC:SIL ratio.

PMID- 16959305
TI  - Paclitaxel, carboplatin and pegylated liposomal doxorubicin in ovarian and
      peritoneal carcinoma: a phase I study of the Gynecologic Oncology Group.
AB  - PURPOSE: Based on the activity and tolerability of liposomal doxorubicin in
      platinum- and paclitaxel-resistant ovarian carcinoma, we conducted a phase I
      trial of pegylated liposomal doxorubicin with paclitaxel and carboplatin to
      determine the maximum tolerated dose (MTD) in chemotherapy naive ovarian,
      peritoneal and tubal carcinoma patients. METHODS: Three schedules were studied:
      paclitaxel, carboplatin and pegylated liposomal doxorubicin every 28 days;
      paclitaxel and carboplatin every 21 days with liposomal doxorubicin every 42
      days; and weekly paclitaxel, carboplatin (AUC=5) every 21 days and liposomal
      doxorubicin every 42 days. The paclitaxel dose was 175 mg/m(2) over 3 h on an
      every 3-4 week schedule and 60 mg/m(2) when administered weekly. Based on the
      frequency of neutropenic sepsis, grade 4 thrombocytopenia and > or =grade 3 non
      hematologic toxicity, the starting dose of liposomal doxorubicin of 20 mg/m(2)
      was escalated to determine the MTD. RESULTS: A total of 210 (21-day) cycles were
      administered to 37 patients. Dose-limiting toxicity (DLT) occurred when liposomal
      doxorubicin was administered at 40 mg/m(2). Because of treatment-related delays
      resulting in decreased paclitaxel/carboplatin dose intensity, administration was
      modified to be given every 21 days, with liposomal doxorubicin given every 42
      days. Since neutropenia was the DLT of this schedule, the schema was further
      modified to administer paclitaxel weekly; however, weekly administration was
      inconsistent because of toxicity. CONCLUSION: Paclitaxel 175 mg/m(2), carboplatin
      (AUC=5) and pegylated liposomal doxorubicin 30 mg/m(2) are tolerable without
      supportive therapy. The usual dose intensity of paclitaxel/carboplatin was
      maintained by administering liposomal doxorubicin every other cycle.

PMID- 16959307
TI  - Smoking in early gestation or through pregnancy: a decision crucial to pregnancy
      outcome.
AB  - OBJECTIVE: To assess maternal risk profile and pregnancy outcome of women who
      continued to smoke, reduced smoking to less than five cigarettes per day or did
      not smoke during pregnancy. METHODS: We analyzed a population-based database of
      26,414 singleton pregnancies from 1989 to 2001. Odds ratios (ORs) for adverse
      pregnancy outcomes were obtained from multiple logistic regression models.
      RESULTS: The prevalence of smoking in early pregnancy was 25.7% and went down to
      12.7% at 20 weeks of pregnancy. Women who smoked were more often young,
      primiparous or unmarried, used alcohol and more often had prior pregnancy
      terminations than women who did not smoke. Women who reduced smoking were mostly
      primiparous, and they also quit using alcohol. Continuing to smoke was associated
      with elevated risks of small-for-gestational-age infants (SGA) (OR 2.11), preterm
      birth (OR 1.15) and perinatal death (OR 1.15). SGA was avoided by reducing
      smoking, but not prematurity (OR 1.18) or elevated risk of perinatal death (OR
      1.18). CONCLUSION: Smoking in early gestation and through pregnancy is associated
      with adverse pregnancy outcomes, and some of the harmful effects can be avoided
      by reducing smoking, although the behavioral risk profile of those who reduced
      smoking is closer to that of smokers than of non-smokers.

PMID- 16959308
TI  - Conventional energy and macronutrient variables distort the accuracy of
      children's dietary reports: illustrative data from a validation study of effect
      of order prompts.
AB  - OBJECTIVE: Validation-study data are used to illustrate that conventional energy
      and macronutrient (protein, carbohydrate, fat) variables, which disregard
      accuracy of reported items and amounts, misrepresent reporting accuracy.
      Reporting-error-sensitive variables are proposed which classify reported items as
      matches or intrusions, and reported amounts as corresponding or overreported.
      METHODS: 58 girls and 63 boys were each observed eating school meals on 2 days
      separated by > or =4 weeks, and interviewed the morning after each observation
      day. One interview per child had forward-order (morning-to-evening) prompts; one
      had reverse-order prompts. Original food-item-level analyses found a sex-x-order
      prompt interaction for omission rates. Current analyses compared reference
      (observed) and reported information transformed to energy and macronutrients.
      RESULTS: Using conventional variables, reported amounts were less than reference
      amounts (ps<0.001; paired t-tests); report rates were higher for the first than
      second interview for energy, protein, and carbohydrate (ps< or =0.049; mixed
      models). Using reporting-error-sensitive variables, correspondence rates were
      higher for girls with forward- but boys with reverse-order prompts (ps< or
      =0.041; mixed models); inflation ratios were lower with reverse- than forward
      order prompts for energy, carbohydrate, and fat (ps< or =0.045; mixed models).
      CONCLUSIONS: Conventional variables overestimated reporting accuracy and masked
      order prompt and sex effects. Reporting-error-sensitive variables are recommended
      when assessing accuracy for energy and macronutrients in validation studies.

PMID- 16959309
TI  - Effect of dietary Vitamin E on the cloacal gland, foam and semen characteristics
      of male Japanese quail.
AB  - This experiment was to investigate the effects of increasing the level of dietary
      Vitamin E (Vit. E) on cloacal gland size, foam production and semen
      characteristics of male Japanese quail (Coturnix coturnix Japonica). One hundred
      and eighty male Japanese quail chicks (day old) were randomly distributed to
      three dietary treatments for a period of 25 weeks. Each treatment comprised of
      three replicates each containing 20 chicks. The basal diet contained 15 IU Vit.
      E/kg and the two experimental diets were supplemented with 150 and 300 IU Vit.
      E/kg (diets T2 and T3, respectively). DL alpha-tocopherol acetate was used as the
      source of Vit. E. All chicks were provided feed and water ad libitum. Foam
      characteristics, in terms of frequency of foam discharge (24h), cloacal gland
      index and foam weight were significantly higher (P<0.05) in T2 group. Body
      weight, testes weight (left and right) and plasma testosterone concentrations did
      not differ significantly. Semen characteristics (semen volume, sperm motility, %
      live sperm, % hatchability and sperm concentrations) did not differ significantly
      (P>0.05). Percentages of abnormal and dead spermatozoa were significantly
      (P<0.05) lower and fertility was higher (P<0.05) in the T2 group. From this
      study, it can be concluded that moderate supplementation of dietary Vit. E may be
      beneficial for foam production, cloacal gland and improve the semen
      characteristics in male Japanese quail.

PMID- 16959310
TI  - Relations between suicidal ideation and dimensions of depressive symptoms in high
      school students.
AB  - The aim of the study was to evaluate the link between the different dimensions of
      depressive symptoms and suicidal ideation in adolescents. A sample of 1057
      adolescents completed the CES-D (Center for Epidemiological Studies Depression
      Scale) and three additional items measuring suicidal ideation. The four
      dimensions of depressive symptoms on the CES-D (Depressed Affect, Loss of
      Positive Affect, Somatic and Retarded Activity, Interpersonal) were entered into
      regression analyses predicting the presence of any suicidal ideation and of the
      wish to kill oneself among participants with moderate/severe depressive symptoms
      (n=271). For both boys and girls Depressed Affect was the main significant
      predictor of the presence of any suicidal ideation and of the wish to kill
      oneself. There were two additional significant predictors for boys: Loss of
      Positive Affect positively predicted the presence of any suicidal ideation;
      Somatic and Retarded Activity negatively predicted the presence of the wish to
      kill oneself.

PMID- 16959311
TI  - Catalytic generation of nitric oxide from S-nitrosothiols using immobilized
      organoselenium species.
AB  - Novel nitric oxide (NO) generating polymeric materials possessing immobilized
      organoselenium species are described. These materials mimic the capability of
      small organoselenium molecules as well as a known selenium-containing enzyme,
      glutathione peroxidase (GPx), by catalytically decomposing S-nitrosothiols (RSNO)
      into NO and the corresponding free thiol. Model polymeric materials, e.g.,
      cellulose filter paper and polyethylenimine, are modified with an appropriate
      diselenide species covalently linked to the polymeric structures. Such
      organoselenium (RSe)-derivatized polymers are shown to generate NO from RSNO
      species in the presence of an appropriate thiol reducing agent (e.g.,
      glutathione). The likely involvement of both immobilized selenol/selenolate and
      diselenide species for NO production is suggested via a catalytic pathway, as
      deduced in separate homogeneous solution phase experiments using non-immobilized
      forms of small organodiselenide species. Preliminary experiments with the new RSe
      polymers clearly demonstrate the ability of such materials to generate NO from
      RSNO species even after the contact with fresh animal plasma. It is anticipated
      that such NO generation from endogenous S-nitrosothiols in blood could render RSe
      containing polymeric materials more thromboresistant when in contact with flowing
      blood, owing to NO's ability to inhibit platelet adhesion and activation.

PMID- 16959312
TI  - Self-assembled, thermosensitive micelles of a star block copolymer based on PMMA
      and PNIPAAm for controlled drug delivery.
AB  - A four-arm star block copolymer, comprised of a hydrophobic PMMA arm and an
      average of three hydrophilic poly(N-isopropylacrylamide) (PNIPAAm) arms were
      designed and synthesized from the molecular level. The amphiphilic star block
      copolymer is capable of self-assembling into micelles in water, which was
      confirmed by FT-IR, (1)H NMR and fluorescence spectroscopy. Transmission electron
      microscopy images showed that these nanoparticles were regularly spherical in
      shape. The micelles showed reversible dispersion/aggregation in response to
      temperature cycles through an outer polymer shell lower critical solution
      temperature (LCST) for PNIPAAm at around 34 degrees C, observed by optical
      absorbance measurements. Resulted polymeric micelles loaded with prednisone
      acetate showed a much improved drug release behavior due to the special micellar
      structure.

PMID- 16959313
TI  - Preparation and characterization of cross-linked collagen-phospholipid polymer
      hybrid gels.
AB  - 2-methacryloyloxyethyl phosphorylcholine (MPC)-immobilized collagen gel was
      developed. Using 1-ethyl-3-(3-dimethyl aminopropyl)-1-carbodiimide hydrochloride
      (EDC) and N-hydroxysuccinimide (NHS), we cross-linked a collagen film in 2
      morpholinoethane sulfonic acid (MES) buffer (EN gel). EN gel was prepared under
      both pH 4.5 and pH 9.0 in order to observe changes in cross-linking ability. To
      cross-link MPC to collagen gel, poly(MPC-co-methacrylic acid) (PMA) having a
      carboxyl group side chain was chosen. E/N gel was added to the MES buffer having
      pre-NHS activated PMA to make MPC-immobilized collagen gel (MiC gel). MiC gel was
      prepared under both acidic and alkaline conditions to observe the changes in the
      cross-linking ability of PMA. X-ray photoelectron spectroscopy showed that the
      PMA was cross-linked with collagen under both acidic and alkaline conditions.
      Differential scanning calorimetry (DSC) results showed that the shrinkage
      temperature increased for the MiC gels and that the increase would be greater for
      the MiC gel prepared under alkaline conditions. The data showed that swelling
      would be less when the MiC gel was prepared under alkaline conditions. The
      biodegradation caused by collagenase was suppressed for the MiC gel prepared
      under alkaline conditions due to stable inter- and intrahelical networks.

PMID- 16959314
TI  - Influence of scaffold physical properties and stromal cell coculture on
      hematopoietic differentiation of mouse embryonic stem cells.
AB  - Recent studies have suggested that three-dimensional (3D) biomaterial-based
      scaffolds and dynamic culture conditions could provide significant enhancement in
      the differentiation efficiency of embryonic stem cells (ESCs). Here we report
      that scaffold physical properties, like pore size, polymer concentration and
      compression modulus as well as specific culture conditions, e.g. cell seeding
      density and coculture with stromal cells can significantly influence
      hematopoietic differentiation of ESCs. PLLA scaffolds of various polymer
      concentrations (7.5%, 10% and 20% w/v) and pore size distributions (<150 microm,
      150-425 microm, >425 microm) were fabricated using a standard solvent casting
      salt leaching method. Mouse R1 ESCs were allowed to differentiate on these
      scaffolds either alone or in coculture with OP9 cells, a bone-marrow derived
      murine stromal cell line. Following one week of culture, cells were detached and
      analyzed using flow cytometry to evaluate the frequency of hematopoietic
      progenitor cells (HPC). Our results indicate that decreasing scaffold pore size
      increases hematopoietic differentiation of ESCs. In addition, increasing polymer
      concentration which resulted in increased scaffold compression modulus also
      provided significantly enhanced hematopoiesis. Furthermore, higher cell seeding
      densities as well as coculture with marrow-derived stromal cells increased HPC
      generation. Collectively, these results indicate that physical and mechanical
      properties of the 3D microenvironment as well as cell-cell and cell-stromal
      interactions might play a significant role in ESC differentiation and therefore
      warrants further investigation to elucidate the molecular mechanisms.

PMID- 16959315
TI  - Placenta accreta: a review of current advances in prenatal diagnosis.
AB  - Placenta accreta is a life-threatening obstetrical condition requiring a
      multidisciplinary approach. Despite identified obstetrical risk factors, the
      diagnosis is often made at the time of delivery. Recent advances in biology could
      allow a prenatal screening of placenta accreta with the identification of
      biological markers in maternal blood including cell-free fetal DNA, placental
      mRNA, and DNA microarray. These promising technologies can detect the presence of
      anomalies and should play a future role in developing a better understanding of
      placental invasion. Ultrasound imaging is popular due to its low cost and
      accessibility and widely used for the screening of placenta location and
      potential abnormal development. This exam is associated with high sensitivity and
      specificity for diagnosis of placenta accreta when specific defined criteria are
      used for the diagnosis. A placental MRI provides a morphological description, as
      well as recently demonstrated topographical information that optimizes diagnosis
      and surgical management. The screening of placenta accreta should be improved
      with the use of a combination of these diagnostic techniques and benefit high
      risk populations with a reduction in morbidity.

PMID- 16959316
TI  - Gemtuzumab ozogamicin-associated sinusoidal obstructive syndrome (SOS): an
      overview from the research on adverse drug events and reports (RADAR) project.
AB  - Gemtuzumab ozogamicin (GO) was approved for marketing in 2000 by the United
      States Food and Drug Administration (FDA) for older patients with relapsed acute
      myeloid leukemia (AML). Four months later, 14 phase II clinical trial
      participants who received novel GO-containing combination chemotherapy regimens
      developed an unexpected hepatic toxicity termed sinusoidal obstructive syndrome
      (SOS) or hepatic veno-occlusive disease (VOD). Investigators associated with the
      Research on Adverse Drug Events and Reports (RADAR) project reviewed safety
      reports for GO included in reports of clinical trials and observational studies,
      interim reports from an FDA mandated Prospective Observational Registry, and the
      Food and Drug Administration's Adverse Event Reporting System. Medline searches
      provided incidence estimates of GO-associated SOS and comparative rates of SOS
      without GO. SOS is characterized by hyperbilirubinemia, painful hepatomegaly,
      ascites, and sudden weight gain developing at a median of 10 days following GO
      administration for patients who did not undergo an allogeneic SCT procedure and
      13 days following an allogeneic SCT for patients who had previously received GO.
      Among adult AML patients who received GO in clinical trials, SOS incidence was 3%
      at doses < or =6 mg/m(2) if administered as monotherapy or in combination with
      non-hepatotoxic agents versus 28% if administered with thioguanine and 15% when
      administered as monotherapy at a dose of 9 mg/m(2). Observational studies
      identified SOS rates between 15% and 40% if an SCT is performed within 3 months
      of GO administration. The FDA mandated Prospective Observational Registry of
      patients who receive care at 60 medical centers has identified GO-associated SOS
      rates of 14% if an SCT is performed and 9% otherwise. Caution is advised when
      administering GO in routine clinical practice, particularly if administered with
      other hepatotoxic agents, at doses and schedules more intensive than those
      approved by the FDA, or within 3 months of a SCT procedure.

PMID- 16959317
TI  - Outcome evaluation of a community center-based program for mothers at high
      psychosocial risk.
AB  - OBJECTIVE: This study reported the outcome evaluation of the "Apoyo Personal y
      Familiar" (APF) program for poorly-educated mothers from multi-problem families,
      showing inadequate behavior with their children. APF is a community-based multi
      site program delivered through weekly group meetings in municipal resource
      centers. METHOD: A total of 340 mothers referred by the municipal social services
      of Tenerife, Spain were assessed; 185 mothers participated in the APF program
      that lasted 8 months, and 155 mothers were in the control group. Pre-post test
      comparisons for the intervention group and post-test comparisons with the control
      group on self-rating measures of maternal beliefs, personal agency and child
      rearing practices were performed. Multivariate tests, t tests and effect sizes
      (ES) were calculated to determine the program effectiveness on the outcome
      measures. RESULTS: Mothers' support of nurturist and nativist beliefs and the
      reported use of Neglect-permissive and Coercive practices significantly decreased
      after program completion whereas the reported use of Inductive practices
      significantly increased. Increases in self-efficacy, internal control and role
      difficulty were also significant in relation to those of the control group. The
      program was especially effective for older mothers, with fewer children, living
      in a two-parent family, in urban areas and with either low or medium educational
      levels. CONCLUSION: The program was very effective in changing the mothers'
      perceived competences and modestly effective in changing their beliefs about
      child development and education and reported child-rearing practices. Changes in
      personal agency are very important for at-risk parents who feel helpless and with
      no control over their lives.

PMID- 16959319
TI  - Enzymatic and spectroscopic studies on the activation or inhibition effects by
      substituted phenolic compounds in the oxidation of aryldiamines and catechols
      catalyzed by Rhus vernicifera laccase.
AB  - The effect of various phenolic compounds on the activity of Rhus vernicifera
      laccase (Lc) has been evaluated using two different substrates, N,N-dimethyl-p
      phenylenediamine and p-tert-butylcatechol. The observed effect strongly depends
      on the phenol employed and involves either a moderate activation, by halophenols,
      or inhibition, by acidic phenols. The collective data are consistent with an open
      active site in Lc, which is capable of accommodating more than one substrate or
      phenol molecule. According to NMR relaxation experiments, a phenol molecule binds
      at an average distance from type 1 Cu of about 6A, while evidence from electron
      paramagnetic resonance (EPR) experiments shows that binding of another phenol
      molecule induces a change, and probably occurs close to, the type 2/type 3
      cluster. The effect of phenolic compounds on Lc reactivity is related to a
      modification of the substrate affinity for the enzyme. This affinity can either
      be increased, probably through pi-stacking or other types of interactions, or
      decreased, due to competition for the same site. In addition, the alteration
      induced in the trinuclear copper cluster has a marked effect on the enzyme
      reactivity. The inhibition observed with acidic phenols is probably due to the
      protonation of an enzyme intermediate produced at the trinuclear site, e.g. the
      peroxy intermediate, that causes the release of hydrogen peroxide and prevents
      the reaction of this intermediate with the substrate.

PMID- 16959318
TI  - In vivo modulation of the Parkinsonian phenotype by Nrf2.
AB  - Oxidative stress has been implicated in the etiology of Parkinson's disease (PD)
      and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of
      PD. In this report we show that Nrf2, a transcription factor that regulates the
      expression of phase 2 and antioxidative enzymes, modulates MPTP neurotoxicity in
      rodents. Nrf2 knockout and wild-type mice were administered MPTP doses ranging
      from 20 to 60mg/kg. Seven days after MPTP administration dopamine transporter
      (DAT) levels were measured using [(125)I]-RTI-121 quantitative autoradiography as
      an index of dopamine terminal integrity in the striatum. The results indicate
      that MPTP administration resulted in a greater loss of DAT levels in the striatum
      of Nrf2 knockout mice than in wild-type at all MPTP doses tested. Activation of
      the Nrf2 pathway by oral administration of the Nrf2 inducer 3H-1,2-dithiole-3
      thione (D3T) to wild-type mice produced partial protection against MPTP-induced
      neurotoxicity. The protective effect of D3T was not due to a change in MPTP
      metabolism since the level of the MPTP metabolite MPP+ was not significantly
      different in the D3T treated striatum relative to vehicle control. Administration
      of D3T to Nrf2 knockout mice did not protect against MPTP neurotoxicity
      suggesting that the Nrf2 pathway is necessary for the D3T-mediated attenuation of
      MPTP neurotoxicity. This study demonstrates the significance of activating
      intrinsic antioxidative mechanisms in an in vivo model of neurodegeneration. The
      in vivo activation of the Nrf2 pathway in the brain may be an important strategy
      to mitigate the effects of oxidative stress in neurodegenerative disorders and
      neurological disease.

PMID- 16959320
TI  - Synthesis, interaction with double-helical DNA and biological activity of the
      water soluble complex cis-dichloro-1,2-propylenediamine-N,N,N',N'-tetraacetato
      ruthenium (III) (RAP).
AB  - The effects exerted by the new complex cis-dichloro-1,2
      propylenediaminetetraacetato ruthenium (III), H[RuCl(2)(PDTA-H(2))] [1, RAP], on
      DNA and cultured tumor cells (ovarian carcinoma TG cell line) were studied. The
      comparative study of circular dichroism (CD) spectra obtained from DNA and RAP
      DNA system evidences the interaction of the complex with DNA. Compound 1 also
      interacted with tumor TG cells to slow their proliferation rate. BrdU
      incorporation was enhanced in cells treated with compound 1, as evidenced by a
      single-cell electrophoresis method (comet assay), in accordance with RAP-induced
      DNA damage. DNA migration of compound 1-treated cells was similar to that induced
      by noxious agents other than cross-linking chemicals. The stability of
      [RuCl(2)(PDTA-H(2))]-DNA binding is suggested by the high degree of damage that
      persisted after removal of compound 1 from the culture medium.

PMID- 16959321
TI  - Sterically hindered complexes of platinum(II) with planar heterocyclic nitrogen
      donors. A novel complex with 1-methyl-cytosine has a spectrum of activity
      different from cisplatin and is able of overcoming acquired cisplatin resistance.
AB  - A very interesting series of water soluble platinum compounds violating some of
      the classical structure-activity relationships, but still showing antitumor
      activity, was reported by Hollis and collaborators some 25 years ago [L.S.
      Hollis, A.R. Amundsenm, E.W. Stern. J. Med. Chem. 32 (1989) 128-136]. The
      compounds, having formula [PtClA(2)L](+) (A(2)=two monodentate or a bidentate
      amine, L=a secondary or tertiary amine or a N-donor heterocycle), were
      characterized by a positive charge and three non-labile N-donor ligands. We have
      extended the investigation to analogous compounds in which 2,9-dimethyl-1,10
      phenanthroline has taken the place of the A(2) ligand(s) and L is 2-picoline (1),
      6-amino-2-picoline (2), or 1-methyl-cytosine (3). The X-ray analysis of 2 has
      revealed a bow-like distortion of the phenanthroline plane, a sloping of the
      phenanthroline plane with respect to the coordination plane, and an overall
      shielding of the metallic core by the ortho substituents of the phenanthroline
      and pyridine ligands. In vitro grow inhibition assays have been performed on the
      most water soluble complex 3. The results indicate that this complex is
      characterized by a potent growth inhibitory activity with mean IC(50) value (in a
      panel of 11 human tumor cell lines) of 1.1 microM to be compared with a mean
      value of 3.8 microM for cisplatin. The same compound also appears to completely
      overcome the acquired cisplatin resistance stemming from reduced uptake or a
      multifocal mechanism, thus pointing to a mechanism of action distinctly different
      from that of cisplatin.

PMID- 16959322
TI  - Interaction of Lambda- and Delta-[Ru(bpy)2(pbmz)](PF6)2 with the oligonucleotide
      duplex d(CGCGAATTCGCG)2.
AB  - The interaction of the enantiomeric complexes Lambda- and Delta
      [Ru(bpy)(2)(pbmz)](PF(6))(2) (bpy=2,2'-bipyridine, pbmz=2-(2'
      pyridyl)benzimidazole) with the DNA duplex d(CGCGAATTCGCG)(2) was investigated by
      means of 2D NMR techniques. The synthesis of the enantiomers was based on the
      optically pure complexes Lambda- and Delta-[Ru(bpy)(2)(py)(2)](2+) and were
      characterized by CD and NMR spectroscopy. NMR data indicate that both enantiomers
      bind weakly to the oligonucleotide, approaching from the minor groove at the
      centre of the helix. The perturbation of the B-DNA conformation is minor with an
      apparent absence of enantioselectivity. Molecular modelling calculations in
      conjunction with the NOE data support the suggestion that more than one binding
      modes are present. The imidazole amine group of the pbmz ligand is probably
      hydrogen bonded to the DNA phosphodiesteric backbone at the AATT step, and this
      may provide an explanation for the diminished enantioselectivity observed.

PMID- 16959323
TI  - Chromium(V) complexes generated in Arthrobacter oxydans by simulation analysis of
      EPR spectra.
AB  - Chromium(V) is an intermediate formed during the reduction of Cr(VI) to Cr(III)
      compounds by various bacteria. However, little is known about the nature,
      localization and reactivity of Cr(V) species in microbial systems. Electron
      paramagnetic resonance (EPR) spectroscopy was used to study the nature of Cr(V)
      complexes generated in basalt-inhabiting Gram-positive Arthrobacter oxydans
      bacteria after exposure to high concentrations of Cr(VI). Numerical simulations
      of the EPR spectroscopic data provide strong evidence for at least two different
      diolato-type oxoCr(V) complexes (I, g(iso)=1.9801; II, g(iso)=1.9796) involving
      bacterial cell wall macromolecules in the Cr(VI)-A. oxydans system. The relative
      concentrations of the two oxoCr(V)-diolato species differ when Cr(VI) is
      incubated with either untreated A. oxydans cells (I:II approximately 50:50) or
      lyophilized cells (I:II approximately 10:90). Based upon the magnitudes of the
      proton superhyperfine coupling constants ((1)H a(iso)) for species I and II, the
      EPR simulation model is unable to distinguish unambiguously whether the oxoCr(V)
      diolato species are linear alkoxides or cyclic diols (carbohydrates). The oxygen
      containing functional groups associated with teichoic acids are the most likely
      candidates for complexation with the Cr(V) ion.

PMID- 16959324
TI  - Enteroviral infections in children with malignant disease: a 5-year study in a
      single institution.
AB  - OBJECTIVES: The clinical presentation, severity and outcome of enteroviral
      infections in children with malignancy were studied. METHODS: All cases of
      enteroviral infections in a University Pediatric Hematology-Oncology Unit were
      assessed, during a 5-year period. RT-PCR, immunohistochemistry and indirect
      immunofluorescence assay were performed to document the enteroviral infection and
      the type of virus. RESULTS: Fifty-five children had documented enteroviral
      infection among 104 patients evaluated for possible enteroviral infection. Severe
      manifestations occurred in 11/55 (20%) patients, such as encephalitis 5/55,
      cardiac involvement 3/55 (1/55 myocarditis, 1/55 dilated cardiomyopathy, 1/55
      ventricular fibrillation) and infection associated hemophagocytic syndrome 3/55.
      Children with lymphoid malignancy had increased incidence of enteroviral
      infections (87%) compared to children with solid tumors (13%). All patients
      received supportive care, intravenous immunoglobulin (IVIG) (30/55 low dose 400
      mg/kg or 25/55 high dose 2 gr/kg) and/or pleconaril (2/55). All patients who
      received high dose of IVIG developed early negative viral load. However, 4 of
      them succumbed. Infection related fatality rate was 14.5% (N=8). CONCLUSIONS:
      Enteroviruses caused more severe and lethal manifestations especially in children
      with lymphoid malignancy. The administration of high dose of IVIG was beneficial
      in viremia. Thus, the early therapeutic intervention with high dose of IVIG may
      improve the outcome.

PMID- 16959325
TI  - Congo red and protein aggregation in neurodegenerative diseases.
AB  - Congo red is a commonly used histological dye for amyloid detection. The
      specificity of this staining results from Congo red's affinity for binding to
      fibril proteins enriched in beta-sheet conformation. Unexpectedly, recent
      investigations indicate that the dye also possesses the capacity to interfere
      with processes of protein misfolding and aggregation, stabilizing native protein
      monomers or partially folded intermediates, while reducing concentration of more
      toxic protein oligomers. Inhibitory effects of Congo red upon amyloid toxicity
      may also range from blockade of channel formation and interference with
      glycosaminoglycans binding or immune functions, to the modulation of gene
      expression. Particularly, Congo red exhibits ameliorative effect in models of
      neurodegenerative disorders, such as Alzheimer's, Parkinson's, Huntington's and
      prion diseases. Another interesting application of Congo red analogues is the
      development of imaging probes. Based on their small molecular size and
      penetrability through blood-brain barrier, Congo red congeners can be used for
      both antemortem and in vivo visualization and quantification of brain amyloids.
      Therefore, understanding mechanisms involved in dye-amyloidal fibril binding and
      inhibition of aggregation will provide instructive guides for the design of
      future compounds, potentially useful for monitoring and treating
      neurodegenerative diseases.

PMID- 16959326
TI  - A novel mouse skeletal muscle-nerve preparation and in vitro model of ischemia.
AB  - The majority of patients in pain clinics are treated for muscle pain yet methods
      to study it in animals are relatively weak compared to methods to study skin
      pain. Here we describe an in vitro muscle-nerve preparation and model of muscle
      ischemia and contractile fatigue in mice. Timed muscle contraction is
      electrically evoked, while single unit activity of muscle sensory neurons and
      muscle contractile force are simultaneously recorded. The muscle is placed in a
      small (<1 mL) chamber where oxygen levels can be manipulated, drugs can be
      applied, and the extracellular milieu can be highly controlled. We demonstrate
      that we can record from sensory afferents that have the properties expected of
      ischemic nociceptors. This method serves for studying the neuronal and molecular
      mechanisms underlying ischemic pains such as angina, intermittent claudication,
      and sickle cell crisis.

PMID- 16959327
TI  - Construction of a sIgA-enhancing anti-Porphyromonas gingivalis FimA vaccine and
      nasal immunization in mice.
AB  - Porphyromonas gingivalis is implicated in the etiology of chronic periodontitis.
      Fimbriae are one of several critical surface virulence factors of P. gingivalis.
      Interleukin 15 (IL-15) is a critical important cytokine for the differentiation
      of B-1 cells into IgA-inducing cells in mucosal tissues and the proliferation of
      B cells. The present study constructed a co-expression plasmid pIRES-fimA:IL-15
      encoding fimbrinllin (FimA), a subunit of fimbriae and IL-15 as a sIgA-enhancing
      anti-P. gingivalis FimA vaccine. The plasmid pIRES-fimA:IL-15 was transfected to
      CHO cells. The expressions of FimA and IL-15 in CHO cells were verified by
      Western blot and ELISA. Mice were immunized with pIRES-fimA:IL-15 via nasal or
      intramucusal route. The results showed that nasal immunization was capable of
      promoting Ag-specific immune responses in the oral region as well as systemic
      immunity. When immunized via nasal route, IL-15 expressed by the plasmid enhanced
      FimA-specific sIgA antibody response. In conclusion, a co-expression plasmid
      pIRES-fimA:IL-15 has been constructed, and when immunized via nasal route,
      antigen-specific sIgA antibody response could be modulated positively in
      immunized mice.

PMID- 16959328
TI  - The role of the proteasome-ubiquitin pathway in regulation of the IFN-gamma
      mediated anti-VSV response in neurons.
AB  - Pharmacologic inhibition of the proteasome resulted in increased NOS-1 protein
      levels and increased NO production by neuronal cells. This correlated with an
      increased antiviral effect of IFN-gamma against the replication of vesicular
      stomatitis virus (VSV) replication in vitro. We also observed that a regulatory
      protein, Protein Inhibitor of NOS-1 (PIN) was down-regulated by IFN-gamma
      treatment, and more ubiquitinated PIN accumulated in IFN-gamma treated neurons.
      In cells of the reticuloendothelial system, IFN-gamma treatment induces the
      expression of a set of low molecular weight MHC-encoded proteins (LMPs), which
      replace the beta-subunit of the proteasome complex during the proteasome
      neosynthesis, resulting in a complex termed the immunoproteasome. LMP2, -7, and 
      10 were induced and the immunoproteasome was generated by IFN-gamma treatment in
      neuronal cells. Importantly, we observed that IFN-gamma induced inhibition of VSV
      protein synthesis was not dependent on ubiquitination.

PMID- 16959329
TI  - Type 1 laryngeal cleft: establishing a functional diagnostic and management
      algorithm.
AB  - OBJECTIVES: To report our experience with all patients diagnosed with type 1
      laryngeal cleft over a period of 3 years in our referral practice and to describe
      a functional diagnostic and management algorithm for children with this disorder.
      METHODS: A prospective longitudinal study in a tertiary care referral center.
      Twenty pediatric patients diagnosed with type 1 laryngeal cleft in a 3-year
      period (5/1/2002-5/1/2005) were included in this study. The incidence, presenting
      symptoms, diagnostic procedures, medical and surgical interventions performed,
      and clinical outcomes were evaluated. RESULTS: The incidence of type 1 laryngeal
      cleft was 7.6%. Among the 20 patients in this study, aspiration with thin liquids
      was the most common presenting symptom (18 patients, 90%). Three patients
      underwent modified barium swallow (MBS) alone, 3 patients underwent functional
      endoscopic evaluation of swallow (FEES) alone, and 11 patients underwent both MBS
      and FEES prior to intraoperative endoscopic evaluation. Four patients (20%) were
      successfully treated with conservative therapy. Sixteen patients (80%) required
      endoscopic surgical repair after failing a course of conservative measures. The
      success rate of surgical repair was 94% (15 out of 16 patients). CONCLUSIONS:
      Type 1 laryngeal cleft can be challenging diagnostically. We propose a functional
      diagnostic and management algorithm that includes MBS, FEES, suspension
      laryngoscopy with bimanual interarytenoid palpation, and a trial of conservative
      therapy, as a way to diagnose and manage type 1 laryngeal cleft prior to
      consideration of surgical repair. If conservative therapy fails, then surgical
      intervention is indicated.

PMID- 16959330
TI  - Methods for effective real-time RT-PCR analysis of virus-induced gene silencing.
AB  - We applied real-time RT-PCR to the analysis of Tobacco rattle virus (TRV)
      mediated virus-induced gene silencing (VIGS) of the phytoene desaturase (PDS)
      gene in Nicotiana benthamiana and tomato. Using a combination of direct
      measurement and mathematical assessment, we evaluated three plant genes,
      ubiquitin (ubi3), elongation factor-1 alpha (EF-1), and actin, for use as
      internal reference transcripts and found that EF-1 and ubi3 were least variable
      under our experimental conditions. Primer sets designed to amplify the 5' or 3'
      regions of endogenous PDS transcripts in tomato yielded similar reductions in
      transcript levels indicating a uniform VIGS-mediated degradation of target RNA.
      By measuring the ratio of the abundance of the PDS insert transcript to the TRV
      coat protein RNA, we established that the PDS insert within TRV was stable in
      both hosts. VIGS in N. benthamiana resulted in complete photo-bleaching of all
      foliar tissue compared to chimeric bleaching in tomato. PDS transcript levels
      were decreased eleven- and seven-fold in photobleached leaves of N. benthamiana
      and tomato, respectively, while sampling tomato leaflets on the basis of age
      rather than visible bleaching resulted in only a 17% reduction in PDS coupled
      with a large leaf-to-leaf variation. There was a significant inverse relationship
      (r2=76%, P=0.01) between the relative abundance of CP RNA and the amount of PDS
      transcript in rTRV::tPDS-infected tomato suggesting that virus spread and
      accumulation are required precursors for successful VIGS in this host.

PMID- 16959331
TI  - Administration of a dual toll-like receptor 7 and toll-like receptor 8 agonist
      protects against influenza in rats.
AB  - Toll-like receptors (TLR) detect conserved molecular patterns expressed by
      pathogens. Detection of the "molecular signature" for RNA viruses including
      influenza has been attributed to TLR3, TLR7, and TLR8. In the present study,
      compound 3M-011 was shown to be a synthetic human TLR7/8 agonist and cytokine
      inducer. 3M-011 was investigated as a stand-alone immune response modifier in a
      rat model of human influenza. Intranasal (IN) administration of 3M-011
      significantly inhibited H3N2 influenza viral replication in the nasal cavity when
      administered from 72 h before IN viral inoculation to 6h after inoculation. Viral
      inhibition correlated with the ability of the TLR7/8 agonist to stimulate type I
      interferon (IFN) and other cytokines such as tumor necrosis factor-alpha,
      interleukin-12, and IFN-gamma from rat peripheral blood mononuclear cells.
      Prophylactic administration of TLR7/8 agonist also suppressed influenza viral
      titers in the lung, which corresponded with local IFN production. The activity of
      the TLR7/8 agonist resulted in greater inhibition of viral titers compared to rat
      recombinant IFN-alpha administered in a comparable dosing regimen. These studies
      indicate that TLR7/8 agonists may have prophylactic and therapeutic benefits in
      the treatment of respiratory viral infections, such as influenza, when
      administered prior to or shortly after viral inoculation.

PMID- 16959332
TI  - Early weaning augments neuroendocrine stress responses in mice.
AB  - Weaning is one of the most important events in early mammalian life. We
      investigated the influence of early weaning on the development of neuroendocrine
      responses to stress in mice. Our study indicated that precocious weaning augments
      anxiety and aggressiveness in mice, and the lack of mother-pup interaction from
      postnatal days 15-21 may account for this phenomenon. A litter of Balb/cA mice
      was divided into two groups, with one group weaned at postnatal day 14 (early
      weaned) and the other at day 21 (normally weaned). Baseline levels of
      corticosterone, corticosterone response to the moderate stress of exposure to the
      elevated plus maze test, and hippocampal glucocorticoid receptor (GR) mRNA
      expression levels in the mice were assayed at the age of 3, 5, and 8 weeks. At 8
      weeks, basal corticosterone levels in early-weaned males were higher than those
      of normally weaned males. Also at 8 weeks, the early-weaned mice showed a higher
      anxiety level in the elevated plus maze test, and responded with greater levels
      of corticosterone secretion than the normally weaned mice. GR expression in the
      early-weaned mice was higher at 3 weeks but lower at 8 weeks. These GR changes
      were observed only in male mice. These results suggest that early weaning
      increases anxiety and enhances neuroendocrine responses to stress and thus
      modulates the development of the neuroendocrine stress system.

PMID- 16959334
TI  - The uptake, distribution and elimination of paralytic shellfish toxins in mussels
      and fish exposed to toxic dinoflagellates.
AB  - We exposed green-lipped mussels Perna viridis and black sea breams Acanthopagrus
      schlegeli to toxic dinoflagellates Alexandrium fundyense to evaluate the
      accumulation, distribution, transformation, and elimination of paralytic
      shellfish toxins (PSTs) in a controlled environmental condition. The mussels were
      fed A. fundyense for 7 days followed by 3 weeks of depuration, and the fish were
      fed toxic clams (pre-exposed to the dinoflagellates) for 5 days followed by 2
      weeks of depuration. The toxin content and the compartmental distribution of PSTs
      were monitored throughout the experiments by high-performance liquid
      chromatography with post-column fluorescence derivatization (HPLC-FLD). This is
      the first report to assess the biokinetics of PSTs in marine fish under dietary
      exposure. The hepatopancreas in the mussels and the viscera in the fish
      accumulated most of the PSTs. Differential elimination of each toxin was observed
      in the mussels. The C2 toxins were eliminated rapidly in all organs; except in
      hepatopancreas, the more potent toxins such as GTX4, were eliminated slower
      during the depuration period. The relative proportions of various PSTs in the
      mussels changed over time, suggesting toxin-specific uptake and elimination
      rates, or biotransformation preferences between toxins. In the fish, the ratio of
      C1/C2 was 3.0 times (p<0.01) higher when compared to the clam tissues, indicating
      that conversion from C2 to C1 might have occurred when the toxin was transferred
      from the clams to the fish. In summary, species differences in uptake,
      distribution and elimination of PSTs were observed between mussels and fish, and
      this may influence trophic transfer of algal toxins in marine organisms.

PMID- 16959333
TI  - Primary cultured cells as sensitive in vitro model for assessment of toxicants-
      comparison to hepatocytes and gill epithelia.
AB  - In an effort to develop cultured cell models for toxicity screening and
      environmental biomonitoring, we compared primary cultured gill epithelia and
      hepatocytes from freshwater tilapia (Oreochromis niloticus) to assess their
      sensitivity to AhR agonist toxicants. Epithelia were cultured on permeable
      supports (terephthalate membranes, "filters") and bathed on the apical with
      waterborne toxicants (pseudo in vivo asymmetrical culture conditions).
      Hepatocytes were cultured in multi-well plates and exposed to toxicants in
      culture medium. Cytochrome P4501A (measured as 7-Ethoxyresorufin-O-deethylase,
      EROD) was selected as a biomarker. For cultured gill epithelia, the integrity of
      the epithelia remained unchanged on exposure to model toxicants, such as 1,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), benzo(a)pyrene B[a]P, polychlorinated
      biphenyl (PCB) mixture (Aroclor 1254), and polybrominated diphenyl ether (PBDE)
      mixture (DE71). A good concentration-dependent response of EROD activity was
      clearly observed in both cultured gill epithelia and hepatocytes. The time-course
      response of EROD was measured as early as 3h, and was maximal after 6h of
      exposure to TCDD, B[a]P and Aroclor 1254. The estimated 6h EC50 for TCDD, B[a]P,
      and Aroclor 1254 was 1.2 x 10(-9), 5.7 x 10(-8) and 6.6 x 10(-6)M. For the
      cultured hepatocytes, time-course study showed that a significant induction of
      EROD took place at 18 h, and the maximal induction of EROD was observed at 24h
      after exposure. The estimated 24h EC50 for TCDD, B[a]P, and Aroclor 1254 was 1.4
      x 10(-9), 8.1 x 10(-8) and 7.3 x 10(-6)M. There was no induction or inhibition of
      EROD in DE71 exposure to both gill epithelia and hepatocytes. The results show
      that cultured gill epithelia more rapidly induce EROD and are slightly more
      sensitive than cultured hepatocytes, and could be used as a rapid and sensitive
      tool for screening chemicals and monitoring environmental AhR agonist toxicants.

PMID- 16959335
TI  - Differences in the copy number of the py235 gene family in virulent and avirulent
      lines of Plasmodium yoelii.
AB  - The 235kDa rhoptry protein (Py235) of Plasmodium yoelii is coded for by a
      multigene family. Py235 has been implicated in host cell selection and virulence
      as antibodies against it have been shown to inhibit invasion of mature red blood
      cells of the normally virulent P. yoelii YM line and at least one member of this
      family directly binds to erythrocytes. Differences in py235 sequence and copy
      number have been postulated to be responsible for the differences in invasion
      phenotype seen in the avirulent P. yoelii YA line and the YM line. The newly
      available sequence data for P. yoelii 17X NL 1.1 has now made it possible to
      investigate this further. A number of approaches including real time PCR was used
      to determine the exact copy number of individual py235. Except for two cases in
      YA and one in YM there are no differences in py235 copy number between the two
      lines and 17X NL 1.1. Analysis of progeny of a genetic cross between YM and an
      avirulent strain AC yield similar limited variations in copy number. This study
      shows that the copy number of py235 in the analyzed P. yoelii strains is
      significantly lower than previous estimates and much more in line with the
      published genome sequence. The lower copy number as well as the limited
      difference of py235 in the virulent lines makes it highly unlikely that these are
      the factors contributing to the differences in invasion observed.

PMID- 16959336
TI  - Idiopatic spontaneous coronary artery dissection and drug-eluting stents.

PMID- 16959337
TI  - Coronary artery ectasia: is it a destructive inflammatory lesion of the vascular
      wall?

PMID- 16959338
TI  - Simultaneous visualization of myocardial scar, no-reflow phenomenon, ventricular
      and atrial thrombi by cardiac magnetic resonance.
AB  - The recognition of complications during acute phase of myocardial infarction
      remains a difficult dilemma. We report a cases where cardiac magnetic resonance
      was able to identify scar tissue, large no-reflow phenomenon, pericardial
      effusion and ventricular and atrial thrombi.

PMID- 16959339
TI  - Metastatic calcification as a subaortic pedunculated mass in a patient with
      chronic renal failure.

PMID- 16959340
TI  - Biventricular myocardial adaptation to different training protocols in
      competitive master athletes.
AB  - BACKGROUND: Conflicting data have been reported about the nature (physiologic
      versus pathologic) of left ventricular (LV) hypertrophy in master athletes. AIM
      OF THE STUDY: To analyze LV and right ventricular (RV) myocardial function in
      master athletes with LV hypertrophy induced by either endurance or strength
      training. METHODS: Standard Doppler echo and colour Doppler Myocardial Imaging
      (DMI) of LV and of RV basal lateral walls were performed in 40 competitive master
      (>45 years) endurance athletes (ATE), in 20 master strength-trained athletes
      (ATS) and 25 age-matched healthy sedentary subjects, all males. By use of DMI,
      the following parameters of myocardial function were assessed: systolic peak
      velocities, precontraction time, contraction time, early (E(m)) and late (A(m))
      diastolic peak velocities, E(m)/A(m) ratio, relaxation time. RESULTS: The two
      groups were comparable for age, but ATS at rest showed higher heart rate,
      systolic blood pressure, and body surface area. LV mass index did not
      significantly differ between the two groups of athletes. However, ATS showed
      increased wall thickness and relative wall thickness, while LV stroke volume and
      both LV and RV end-diastolic diameters were greater in ATE. All transmitral and
      transtricuspid Doppler indexes were higher in ATE. DMI analysis showed in ATE
      higher E(m) and E(m)/A(m) ratio at the level of both RV and LV lateral walls. In
      the overall population of athletes, linear regression models evidenced
      independent positive association of RV peak E(m) velocity with both LV stroke
      volume and maximal workload achieved by bicycle ergometer (both p<0.001).
      CONCLUSIONS: RV early diastolic myocardial function is positively influenced by
      preload increase in master athletes and represents an independent determinant of
      cardiac performance during physical effort. Therefore, colour DMI may be taken
      into account to distinguish different cardiac adaptation to either endurance or
      strength sport training in master athletes.

PMID- 16959341
TI  - Assessment of factors affecting plasma BNP levels in patients with chronic atrial
      fibrillation and preserved left ventricular systolic function.
AB  - BACKGROUND: Several studies have reported that plasma brain natriuretic peptide
      (BNP) levels are increased in patients with chronic atrial fibrillation (AF). The
      objective of this study was to assess the factors influencing plasma BNP levels
      in patients with chronic AF and preserved left ventricular (LV) systolic
      function. METHODS: Transthoracic echocardiography was performed in 104 patients
      (48 men, 56 women; mean age, 63.9+/-10.7 years) with chronic AF. At the same
      time, plasma BNP levels were measured with a Triage kit (Biosite, San Diego, CA).
      RESULTS: Women, long duration of AF, and hypertension were more prevalent in the
      highest quartile group of BNP levels than in the lowest quartile of BNP.
      Significant correlations were observed between plasma BNP levels and the
      following: mitral E velocity (r=0.343), mitral annular E' velocity (r=-0.402),
      ratio of mitral E velocity and mitral annular E' velocity (r=0.487), left
      atrial(LA) size (r=0.653), LA volume index (r=0.775), right atrial (RA) volume
      index (r=0.563), maximal velocity (V(max)) of mitral regurgitation (MR)
      (r=0.448), tricuspid regurgitation (TR) V(max) (r=0.532) and LV mass index
      (r=0.581). In stepwise multiple linear regression analysis, LA volume index
      (beta=0.326, p<0.001), LV mass index (beta=0.395, p<0.001) and duration of AF
      (beta=0.492, p<0.001) independently predicted plasma BNP levels in the study
      subjects. The patients with increased LA volume index exhibited a longer duration
      of AF, larger RA volume index and LV mass index, higher MR V(max), TR V(max) and
      plasma BNP level. CONCLUSIONS: LA volume index, LV mass index and duration of AF
      are independent predictors of plasma BNP levels in patients with chronic AF and
      preserved LV systolic function.

PMID- 16959342
TI  - Nucleotide polymorphisms associated with Internal Transcribed Spacer (ITS)
      regions of ocular isolates of Aspergillus flavus.
AB  - PURPOSE: To analyse the genetic similarity among ocular isolates of Aspergillus
      flavus by Polymerase chain reaction based Restriction Fragment Length
      Polymorphism (PCR-RFLP) and DNA sequencing. MATERIALS AND METHODS: Seven ocular
      isolates of A. flavus from 5 patients (3 from paient 1, and four isolates from
      patients no. 2, 3, 4, and 5 respectively) consisting of 2 Aqueous Humor (AH), 2
      Vitreous fluid (VF), 1 eviscerated material, 1 corneal button were included in
      the study. The three specimens from 1 were one each of AH, VF and corneal button.
      The fungal isolates were amplified using primers targeting ITS region and the
      amplicons were subjected to PCR-RFLP using Hae-III enzyme and DNA sequencing to
      analyse the genetic similarity. RESULTS: A. flavus isolates yielded a specific
      product of 595 bp after amplification. All the seven A. flavus isolates showed
      similar pattern of digestion with Hae-III . However, DNA sequencing of ITS
      amplicons revealed 97.7% genetic similarity and 2.3% dissimilarity with
      nucleotide polymorphisms -- single, double and multiple pertaining to inversion,
      substitution, insertion and deletion in comparison with that of standard strain
      of A. flavus ATCC 16883 [Accession Number ]. A. flavus isolated from AH, VF and
      corneal button from the same patient showed similar nucleotide polymorphisms as
      against other isolates which exhibited distinct polymorphisms. This pattern of
      nucleotide polymorphisms in A. flavus isolates is novel and first time reported
      in literature to the best of our knowledge. CONCLUSION: DNA sequencing proves to
      be a useful molecular tool in screening for nucleotide polymorphisms among fungal
      isolates.

PMID- 16959343
TI  - New shielding materials for clinical electron beams.
AB  - Since lead has recently been recognized as a source of environmental pollution,
      we have investigated new electron shielding materials that do not contain lead.
      We compared the shielding thicknesses of a hard plate and a sheet composed of the
      new materials with that of lead for electron beams. The shielding thickness was
      evaluated as the thickness required for shielding primary electrons. The
      comparison revealed the shielding ability of the hard plate and sheet is
      approximately equivalent to 1.0 and 0.9 times that of lead, respectively. The
      thickness (in millimeters) required for shielding by the hard-plate, as well as
      the thickness of lead, is related to approximately half of the electron-beam
      energy (in MeV). The shielding ability of the sheet is also equivalent to that of
      Lipowitz alloy. Moreover these materials are environmentally friendly, and can be
      easily customized into arbitrary shapes. Therefore they can be used as lead
      substitutes for shielding against electron beams.

PMID- 16959344
TI  - Emptying the rectum before treatment delivery limits the variations of rectal
      dose - volume parameters during 3DCRT of prostate cancer.
AB  - PURPOSE: To investigate the impact of rectum motion on dose - volume histograms
      of the rectum including filling and of the wall (DVH and DWH, respectively),
      during 3D-conformal radiotherapy (3DCRT) for localized prostate cancer. MATERIALS
      AND METHODS: Ten patients received a planning CT scan (CT(0)) and 11-14 CT during
      3DCRT for prostate cancer (total CT scans=126). CT images were 3D matched using
      bony anatomy. A single observer drew the external contours of rectum and rectum
      wall and the CTV (prostate + seminal vesicles) on CT(0). Patients were asked to
      empty their rectum before every CT, as generally performed at the Institute for
      Cancer Research and Treatment (IRCC) before treatment delivery. Bladder was kept
      full by drinking 500 cm(3) of water 60 min before the scan, according to our
      protocol. A 4-field box 3DCRT technique was planned and dose statistics/dose -
      volume histograms of the rectum were calculated for each contour referred to
      CT(0),CT(1),...,CT(n) for each patient. Average DVHs during treatment were
      calculated along with their standard deviation (SD(rand)) and compared to the
      planned DVH. The analyses on the patient population included the assessment of
      systematic deviation (average difference and SD, named SD(sys)) as well as the
      average SD(rand) value expressing the random component of organ motion. Rectum
      shifts were also assessed by anterior and lateral BEV projections. RESULTS: As to
      the rectum, 8/10 patients showed a "better" average DVH than DVH on CT(0).
      Wilcoxon test showed a statistically significant reduction when correlating the
      difference Delta between the average DVH during therapy and planning DVH at
      CT(0): for instance V(70)Delta = -3.6% and p = 0.022, V(50)Delta = -5.5% and p =
      0.022, D(med)Delta = -3.2 Gy and p = 0.007. Average values of DVH systematic
      difference (average difference between planning scan and treatment), standard
      deviations (SD(sys)) and average standard deviations of the random fluctuation
      (SD(random)) were -4.0%, 4.7% and 6.6%, respectively. Whilst the fluctuation
      results were slightly smaller for DWH. Volume analysis showed a slight systematic
      variation of the rectal volume between planning and treatment BEV. The average
      rectal volume during therapy was larger than at the planning CT in 8/10 patients.
      The systematic shifts of the rectal wall between the planning phase and the
      treatment were rather small, both below and above the flexure. The larger random
      fluctuation of the rectum shape was found to be in the cranial half (1 SD=4.4
      mm). CONCLUSIONS: The practice of carefully emptying the rectum during simulation
      and therapy for prostate cancer, which is a safe and simple procedure, reduces
      the impact of organ motion on dose - volume parameters of the rectum.

PMID- 16959345
TI  - Esophageal cancer: determination of internal target volume for conformal
      radiotherapy.
AB  - BACKGROUND AND PURPOSE: To evaluate esophageal tumor and OAR movement during the
      respiratory cycle in order to obtain optimal values for ITV and PRV. To correlate
      tumor motion with chest wall displacement - information of value in the free
      breathing gating system. MATERIAL AND METHOD: Inclusion criteria were:
      histologically proven squamous-cell carcinoma (SCC) or adenocarcinoma at stage T3
      - T4 NX or TX N1 M0 according to the UICC 1997 classification. Two spiral scans
      were performed with breath-hold respiration under spirometric control: one at end
      expiration (EBH) and the other at end inspiration (IBH). Displacements between
      exhalation and inhalation were calculated according to ICRU report 42
      recommendations. For the correlation study, CT-scan acquisition was performed at
      the isocenter over a 20 - 40 s period. After Fourier Transform, frequency spectra
      for amplitude and phase of tumor and chest wall motions were performed for each
      patient. RESULTS: Cumulative distribution of CTV motion in absolute values showed
      that 95% of data ranged from 0 to 1 cm. Cumulative distribution of GTV motion in
      absolute values showed that 95% of data ranged from 0 to 0.8 cm. The correlation
      study demonstrated no specific relationship between respiratory and esophageal
      motions. CONCLUSION: The ITV margin for 3D conformal radiotherapy in esophageal
      cancer was 1 cm when 95% of motions were taken into account in this clinical
      study involving eight patients. Before using a free-breathing gating system, the
      correlation between external markers and target displacement during irradiation
      must be established for each patient.

PMID- 16959346
TI  - Palliative treatment of Erdheim-Chester disease with radiotherapy: a Rare Cancer
      Network study.
AB  - A retrospective study of the use of palliative external beam radiotherapy (EBRT)
      in nine patients with Erdheim-Chester disease was conducted through the Rare
      Cancer Network. Patients received EBRT for bone pain, brain infiltration, or
      retro-orbital involvement. EBRT typically provided short-term palliation, with
      later recurrence of symptoms in most cases.

PMID- 16959347
TI  - Intensified local treatment and systemic therapy significantly increase survival
      in patients with brain metastases from advanced breast cancer - a retrospective
      analysis.
AB  - BACKGROUND: Brain metastases have evolved from a rare to a frequently encountered
      event in advanced breast cancer due to advances in palliative systemic treatment.
      PATIENTS AND METHODS: All Patients treated at our centre from 1994 to 2004 with
      WBRT for brain metastases from breast cancer were included. We performed a
      multivariate analysis (Cox regression) to explore which factors are able to
      influence significantly cerebral time to progression (TTP) and overall survival
      (metastatic sites [visceral versus non-visceral], Karnofsky performance score
      [KPS], age, intensified local treatment [boost irradiation, neuro-surgical
      resection] further systemic treatment). RESULTS: Overall 174 patients, median age
      51 years, range 27-76 years, were included. Median TTP was 3 months (m), range 1
      33+ m. Median overall survival was 7 m, range 1-44 m. Factors significantly
      influencing TTP were KPS (p = 0.002), intensified local treatment (p < 0.001),
      and palliative systemic treatment (p = 0.001). Factors significantly influencing
      survival were intensified local treatment (p = 0.004), metastatic sites (p =
      0.008), KPS (p = 0.006), and palliative systemic treatment (p < 0.001).
      CONCLUSION: As shown by the significant influence of metastatic sites, some
      patients die from their advanced systemic tumour situation before they would die
      from cerebral progression. In other individuals however, intensified local
      treatment and systemic treatment appear to influence cerebral time to progression
      and overall survival.

PMID- 16959348
TI  - What's that sound? Matches with auditory long-term memory induce gamma activity
      in human EEG.
AB  - In recent years the cognitive functions of human gamma-band activity (30-100 Hz)
      advanced continuously into scientific focus. Not only bottom-up driven influences
      on 40 Hz activity have been observed, but also top-down processes seem to
      modulate responses in this frequency band. Among the various functions that have
      been related to gamma activity a pivotal role has been assigned to memory
      processes. Visual experiments suggested that gamma activity is involved in
      matching visual input to memory representations. Based on these findings we
      hypothesized that such memory related modulations of gamma activity exist in the
      auditory modality, as well. Thus, we chose environmental sounds for which
      subjects already had a long-term memory (LTM) representation and compared them to
      unknown, but physically similar sounds. 21 subjects had to classify sounds as
      'recognized' or 'unrecognized', while EEG was recorded. Our data show
      significantly stronger activity in the induced gamma-band for recognized sounds
      in the time window between 300 and 500 ms after stimulus onset with a central
      topography. The results suggest that induced gamma-band activity reflects the
      matches between sounds and their representations in auditory LTM.

PMID- 16959349
TI  - Jackson and the frontal executive hierarchy.
AB  - Executive actions are represented and hierarchically organized in the cortex of
      the frontal lobe. The representation and coordination of an action or series of
      actions have the same anatomical substrate: an executive neuronal network
      (cognit) in forntal cortex. That network interacts structurally and dynamically
      with perceptual networks of posterior cortex at the highest levels of the
      perception-action cycle.

PMID- 16959350
TI  - Select what you need: a comparative evaluation of the advantages and limitations
      of frequently used expression systems for foreign genes.
AB  - The expression of heterologous proteins in microorganisms using genetic
      recombination is still the high point in the development and exploitation of
      modern biotechnology. People can produce bioactive proteins from relatively cheap
      culture medium instead of expensive extraction. Host cell systems for the
      expression of heterologous genes are generally prokaryotic or eukaryotic systems,
      both of which have inherent advantages and drawbacks. An optimal expression
      system can be selected only if the productivity, bioactivity, purpose, and
      physicochemical characteristics of the interest protein are taken into
      consideration, together with the cost, convenience and safety of the system
      itself. Here, we concisely review the most frequently used prokaryotic, yeast,
      insect and mammalian expression systems, as well as expression in eukaryote
      individuals. The merits and demerits of these systems are discussed.

PMID- 16959351
TI  - An effective cold inducible expression system developed in Pseudoalteromonas
      haloplanktis TAC125.
AB  - A regulative two-component system previously identified in Pseudoalteromonas
      haloplanktis TAC125 was used to construct a cold inducible expression system that
      is under the control of l-malate. Performances of the inducible system were
      tested for both psychrophilic and mesophilic protein production using two
      "difficult" proteins as control. The results obtained demonstrated that both
      psychrophilic beta-galactosidase and yeast alpha-glucosidase are produced in a
      fully soluble and catalytically competent form. Optimal conditions for protein
      production, including growth temperature, growth medium and l-malate
      concentration were also investigated. Under optimized conditions yields of 620
      and 27 mg/l were obtained for beta-galactosidase and alpha-glucosidase,
      respectively.

PMID- 16959352
TI  - Heterologous production and secretion of Clostridium perfringens beta-toxoid in
      closely related Gram-positive hosts.
AB  - The spore forming bacterium Clostridium perfringens is a widely occurring
      pathogen. Vaccines against C. perfringens type B and C are currently manufactured
      using beta-toxin secreted by virulent C. perfringens strains. Large-scale
      production of vaccines from virulent strains requires stringent safety conditions
      and costly detoxification and control steps. Therefore, it would be beneficial to
      produce this toxin in a safe production host and in an immunogenic, but non-toxic
      form (toxoid). For high-level expression of beta-toxoid, we cloned the highly
      active ribosomal rpsF promoter of Bacillus subtilis in a broad host range
      multicopy plasmid. In B. subtilis, we obtained high intracellular production, up
      to 200 microg ml(-1) culture. However, the beta-toxoid was poorly secreted. The
      employed rpsF expression system allowed using the same expression plasmids in
      other heterologous hosts such as Lactococcus lactis and Streptococcus pneumoniae.
      In these organisms secretion of beta-toxoid was ten times higher compared to the
      best producing B. subtilis strain. These results show the usefulness of the rpsF
      based broad host range expression system.

PMID- 16959353
TI  - A kinetic study of isoamyl acetate synthesis by immobilized lipase-catalyzed
      acetylation in n-hexane.
AB  - The objective of this work was to propose a reaction mechanism and to develop a
      rate equation for the synthesis of isoamyl acetate by acylation of the
      corresponding alcohol with acetic anhydride using the lipase Novozym 435 in n
      hexane. The reaction between isoamyl alcohol and acetic anhydride occurred at
      high rate in first place. Then, if excess alcohol was used, produced acetic acid
      further reacted with remaining alcohol, leading to yields higher than 100% (based
      on initial acetic anhydride content). This reaction was much slower and took
      place only when acetic anhydride had been totally consumed. Optimal pH for
      Novozym 435 was 7.7. Acetic acid strongly inactivated the enzyme but it was
      partially caused by the pH drop in the biocatalyst aqueous microenvironment.
      Acetic anhydride also showed an important inhibition effect. On the contrary,
      isoamyl alcohol and isoamyl acetate had no negative effect on the lipase. The
      analysis of the initial rate data showed that reaction followed a Ping-Pong Bi-Bi
      mechanism with inhibition by acetic anhydride. The kinetic constants were
      obtained by multiple regression analysis of experimental findings. Equation
      predictions and experimental reaction rate values matched very well at conditions
      where acetic acid concentration in the medium was low.

PMID- 16959354
TI  - Downstream processing of triple layered rotavirus like particles.
AB  - Rotavirus like particles (RLPs) constitute a potential vaccine for the prevention
      of rotavirus disease, responsible for the death of more than half a million
      children each year. Increasing demands for pre-clinical trials material require
      the development of reproducible, scaleable and cost-effective purification
      strategies as alternatives to the traditional laboratory scale CsCl density
      gradient ultracentrifugation methods commonly used for the purification of these
      complex particles. Self-assembled virus like particles (VLPs) composed by VP2,
      VP6 and VP7 rotavirus proteins (VLPs 2/6/7) were produced in 5l scale using the
      insect cells/baculovirus expression system. A purification process using depth
      filtration, ultrafiltration and size exclusion chromatography as stepwise unit
      operations was developed. Removal of non-assembled rotavirus proteins,
      concurrently formed particles (RLP 2/6), particle aggregates and products of
      particle degradation due to shear was achieved. Particle stability during storage
      was studied and assessed using size exclusion chromatography as an analytical
      tool. Formulations containing either glycerol (10% v/v) or trehalose (0.5 M) were
      able to maintain 75% of intact triple layered VLPs, at 4 degrees C, up to 4
      months. The overall recovery yield was 37% with removal of 95% of host cell
      proteins and 99% of the host cell DNA, constituting a promising strategy for the
      downstream processing of other VLPs.

PMID- 16959355
TI  - Difference in production of infectious wild-type measles and vaccine viruses in
      monocyte-derived dendritic cells.
AB  - Macrophages (Mo) and dendritic cells (DC) are thought to be targets of measles
      virus (MeV) at the early stage of infection. We compared the growth of Edmonston
      derived vaccine strains and fresh clinical isolates of MeV in monocytes, monocyte
      derived granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced Mo (GM
      Mo) and in monocyte-derived DC (Mo-DC). Neither vaccine strains nor fresh
      isolates thrived in monocytes and GM-Mo and no differences were evident among
      them. On the other hand, infectious virus production was robust in Mo-DC infected
      with fresh isolates, but below the limits of detection in those infected with
      vaccine strains. Although the vaccine strains infected Mo-DC and replicated
      comparably with the fresh isolates, they accumulated far less matrix (M) protein.
      This was attributed to a difference in the stability of M protein produced in Mo
      DC between the strains. Impaired production of infectious viruses in DC may be
      one cause of vaccine strain attenuation.

PMID- 16959356
TI  - Floating hot-melt extruded tablets for gastroretentive controlled drug release
      system.
AB  - The purpose of this study was to investigate the influence of sodium bicarbonate
      on the physicochemical properties of controlled release hot-melt extruded (HME)
      tablets containing Eudragit RS PO and/or Eudragit E PO. Acetohydroxamic acid and
      chlorpheniramine maleate were used as model drugs. Sodium bicarbonate was
      incorporated into the tablet formulations and the drug release properties and
      buoyancy in media for HME tablets and directly compressed (DC) tablets were
      investigated. The HME tablets prepared from the powder blend containing both
      Eudragit RS PO and sodium bicarbonate exhibited sustained release properties and
      the tablets floated on the surface of the media for 24 h. The cross-sectional
      morphology of the HME tablets showed a porous structure since CO(2) gas was
      generated due to the thermal decomposition of sodium bicarbonate in the softened
      acrylic polymers at elevated temperature during the extrusion process. In
      contrast, all DC tablets prepared in this study showed no buoyancy and rapid drug
      release in the dissolution media. The drug release rate from floating HME tablets
      was controlled by both the incorporation of Eudragit E PO into the matrix tablet
      and the diameter of the die used in the extrusion equipment. The drug release
      profiles and buoyancy of the floating HME tablets were stable when stored at 40
      degrees C/75%RH for 3 months.

PMID- 16959357
TI  - Submicron lipid emulsion as a drug delivery system for nalbuphine and its
      prodrugs.
AB  - This study investigates the submicron lipid emulsion as a potential parenteral
      drug delivery system for nalbuphine and its ester prodrugs. Submicron emulsions
      were prepared using egg phospholipid as the main emulsifier, various co
      emulsifiers were also incorporated, including Brij 30, Brij 98, and stearylamine.
      Squalene as the oil phase formed stable emulsions with small particles. Drug
      release was affected by incorporating various co-emulsifiers and drugs with
      various lipophilicity. The loading of nalbuphine into lipid emulsions resulted in
      the slower and sustained release of nalbuphine. Lipid emulsions containing Brij
      98 could further enhance the release of prodrugs as compared to the aqueous
      solution (control) especially for nalbuphine enanthate (NAE). Hemolysis caused by
      the interaction between erythrocytes and lipid emulsions was investigated. Brij
      30 and Brij 98 could shield the hemolytic activity of phospholipids in the
      oil/water interface, decreasing the acute toxicological potential of the
      emulsions. The in vivo analgesic activity of various emulsions was examined by a
      cold ethanol tail-flick test. The analgesic duration and potency were
      significantly increased by incorporating nalbuphine and NAE into Brij 98
      containing emulsions. There was no need for nalbuphine benzoate (NAB) to show a
      controlled delivery manner by encapsulating into emulsions, since NAB itself
      could prolong the analgesic duration of nalbuphine due to the slow enzyme
      degradation. The in vivo analgesic activity correlated well to the profiles of in
      vivo pharmacokinetic profiles. The study demonstrates the feasibility of using
      submicron lipid emulsion as the parenteral drug delivery system for nalbuphine
      and its prodrugs.

PMID- 16959358
TI  - Development and characterisation of chitosan nanoparticles for siRNA delivery.
AB  - Gene silencing mediated by double-stranded small interfering RNA (siRNA) has been
      widely investigated as a potential therapeutic approach for diseases with genetic
      defects. The use of siRNA, however, is hampered by its rapid degradation and poor
      cellular uptake into cells in vitro or in vivo. Therefore, we have explored
      chitosan as a siRNA vector due to its advantages such as low toxicity,
      biodegradability and biocompatibility. Chitosan nanoparticles were prepared by
      two methods of ionic cross-linking, simple complexation and ionic gelation using
      sodium tripolyphosphate (TPP). Both methods produced nanosize particles, less
      than 500 nm depending on type, molecular weight as well as concentration of
      chitosan. In the case of ionic gelation, two further factors, namely chitosan to
      TPP weight ratio and pH, affected the particle size. In vitro studies in two
      types of cells lines, CHO K1 and HEK 293, have revealed that preparation method
      of siRNA association to the chitosan plays an important role on the silencing
      effect. Chitosan-TPP nanoparticles with entrapped siRNA are shown to be better
      vectors as siRNA delivery vehicles compared to chitosan-siRNA complexes possibly
      due to their high binding capacity and loading efficiency. Therefore, chitosan
      TPP nanoparticles show much potential as viable vector candidates for safer and
      cost-effective siRNA delivery.

PMID- 16959359
TI  - PEGylated gene nanocarriers based on block catiomers bearing ethylenediamine
      repeating units directed to remarkable enhancement of photochemical transfection.
AB  - The therapeutic usefulness of macromolecular drugs such as plasmid DNA is often
      limited by the inefficient transfer of macromolecules to the cytosol.
      Photochemical internalization (PCI) technology, in which the endosomal escape of
      DNA or its complex is assisted by co-incubated photosensitizers that photodamage
      endosome membrane, offers a solution for this problem. A series of poly(ethylene
      glycol) (PEG)-based block polycatiomers with increasing number of ethylenediamine
      repeating unit at side chain of polycatiomers were complexed with pDNA to form
      the PEGylated polyplexes as a biocompatible gene carrier. Dendrimeric
      phthalocyanine (DPc)-incorporated micelle was used to assist the gene transfer of
      these polyplexes in a light-inducible manner. As a result, the light-inducible
      transfection activity was significantly enhanced as the number of amino group at
      the side chain of PEG-b-polycatiomer increased. The polyplex from PEG-b
      polycatiomer having the longest ethylenediamine structure achieved approximately
      1000-fold enhancement of transfection upon photoirradiation. This result supports
      the underlying hypothesis that photochemical transfection and proton sponge
      effect of polycations can work synergistically to enhance the transfection
      efficiency. With careful balance between photochemical transfection enhancement
      and cytotoxicity, PEG-b-polycatiomers used in this study might be a potential
      candidate for in vivo PCI-mediated gene transfer.

PMID- 16959360
TI  - A thermally responsive biopolymer for intra-articular drug delivery.
AB  - Intra-articular drug delivery is the preferred standard for targeting
      pharmacologic treatment directly to joints to reduce undesirable side effects
      associated with systemic drug delivery. In this study, a biologically based drug
      delivery vehicle was designed for intra-articular drug delivery using elastin
      like polypeptides (ELPs), a biopolymer composed of repeating pentapeptides that
      undergo a phase transition to form aggregates above their transition temperature.
      The ELP drug delivery vehicle was designed to aggregate upon intra-articular
      injection at 37 degrees C, and form a drug 'depot' that could slowly disaggregate
      and be cleared from the joint space over time. We evaluated the in vivo
      biodistribution and joint half-life of radiolabeled ELPs, with and without the
      ability to aggregate, at physiological temperatures encountered after intra
      articular injection in a rat knee. Biodistribution studies revealed that the
      aggregating ELP had a 25-fold longer half-life in the injected joint than a
      similar molecular weight protein that remained soluble and did not aggregate.
      These results suggest that the intra-articular joint delivery of ELP-based fusion
      proteins may be a viable strategy for the prolonged release of disease-modifying
      protein drugs for osteoarthritis and other arthritides.

PMID- 16959361
TI  - DNA polyplexes based on degradable oligoethylenimine-derivatives: combination
      with EGF receptor targeting and endosomal release functions.
AB  - Combination of the degradable polymeric gene carriers OEI-HD-1 and LT- OEI-HD-1
      with an EGF targeting conjugate resulted in strongly (up to 900-fold) enhanced
      polyplex activity in EGF-receptor rich HUH7 hepatocellular carcinoma cells. The
      targeting ligand effect was DNA dose dependent, could be blocked by competitive
      receptor binding with unbound EGF ligand, and was not observed in receptor
      negative control cells. Measures which enhance intracellular endosomal escape,
      either photochemically enhanced intracellular release (PCI) or the incorporation
      of a novel membrane-active melittin analog NMA-3, further enhanced gene transfer
      activity of EGF/OEI-HD-1 polyplexes.

PMID- 16959362
TI  - Acute anuric renal failure secondary to intravenous immunoglobulin in diabetic
      nephropathy.
AB  - We present a case of acute renal failure in a diabetic patient who received
      intravenous immunoglobulin therapy. Vigam liquid immunoglobulin was used
      successfully to treat vancomycin induced toxic epidermal necrolysis, but 4 days
      later the patient became anuric. Renal function was restored after
      haemofiltration. Immunoglobulin therapy is used to treat immune-mediated
      conditions, many of which affect the diabetic population. Renal failure is a rare
      side effect of immunoglobulin in patients with diabetes and impaired renal
      function, of which many clinicians are unaware. Caution must be exercised in such
      patients and the risks of immunoglobulin treatment weighed against the benefits.

PMID- 16959363
TI  - Diabetic ketoacidosis in Denmark Incidence and mortality estimated from public
      health registries.
AB  - The aims of this study were to estimate incidence of diabetic ketoacidosis and
      mortality from diabetic ketoacidosis using data from public health registries.
      Four thousand eight hundred and seven admissions in the period 1996-2002 and 137
      deaths in the period 1996-2000 with a diagnosis of diabetic ketoacidosis were
      identified from the Danish National Patient Registry and Danish Cause of Death
      Registry, respectively. Annual incidence of diabetic ketoacidosis in the general
      population was estimated to 12.9 per 100,000, being higher in males than in
      females (14.4 versus 11.4 per 100,000, p<0.0001). Twelve percent of all patients
      were classified as Type 2 diabetes, predominantly in patients >50 years. Overall
      mortality was 4%, being higher in patients >70 years than in patients < or =70
      years (15% versus 2%, p<0.0001). One or more additional somatic diagnoses were
      stated on 77% of the death certificates, most often a diagnosis of cardiovascular
      (47%) or infectious (30%) diseases. Compared to previous studies, the incidence
      in the general population seems to have remained unaltered the past 25 years, but
      may have decreased in younger patients. Older patients with diabetic ketoacidosis
      differed from younger patients in having a higher mortality and a larger
      proportion of patients classified as Type 2 diabetes.

PMID- 16959364
TI  - The spontaneously diabetic Torii rat with gastroenteropathy.
AB  - The spontaneously diabetic Torii (SDT) rat was recently recognized as a new
      animal model of non-obese type 2 diabetes. As the severe diabetic ocular
      complications seen in SDT rats already have been investigated, we examined
      another common diabetic complication, gastroenteropathy. Male SDT rats developed
      diabetes at 20 weeks and diarrhea at 28 weeks of age. Gastrointestinal motility
      was evaluated at 28 weeks by measuring the distance of small intestinal transit
      by oral administration of the non-absorbed marker, arabic gum. SDT rats exhibited
      greater intestinal transit distance than control SD rats (54.1+/-2.6% versus
      43.0+/-1.2%). Insulin treatment of SDT rats begun at 20 weeks of age produced
      improved stool and reduced intestinal transit distance (41.4+/-0.3%).
      Morphologically, the SDT rats exhibited longer villi and heavier weight of
      intestine compared to control SD rats. These results suggest that the SDT rat may
      be a useful animal model for studies of diabetic gastroenteropathy.

PMID- 16959365
TI  - Lactate and ventilatory thresholds in type 2 diabetic women.
AB  - Anaerobic threshold (AT) has been considered the optimal exercise intensity for
      type 2 diabetes mellitus (DM 2) patients, but there is little information about
      the comparison between lactate (LT) and ventilatory (VT) thresholds in this
      population, particularly during treadmill exercise. Therefore, we evaluated DM 2
      women in order to compare and analyze the relationships between VT and LT
      intensities. Fifteen women with DM 2 without complications and comorbidities
      (50.7 +/- 8.0 years; 71.3 +/- 8.6 kg; 154 +/- 5 cm; 37.8 +/- 3.9% fat; 4.7 +/-
      3.2 years of disease diagnose and 138 +/- 45 mg/dl fasting glucose) were
      subjected to a graded treadmill test-initial velocity and increments of 1 km/h
      every 2 min until voluntary exhaustion. VT was determined from V(E)/V(O(2)) and
      V(E)-V(CO(2)) ratios and LT was defined as the point at which a first increase in
      blood lactate occurs during incremental test. Our results showed no significant
      differences (p > 0.05) and significant correlations between VT and LT expressed
      in velocity (4.7 +/- 0.7 versus 4.6 +/- 0.7 km/h, r = 0.62), absolute V(O(2))
      (1.27 +/- 0.33 versus 1.24 +/- 0.28 l min(-1), r = 0.93); relative V(O(2)) (18.3
      +/- 5.7 versus 17.6 +/- 4.6 ml kg(-1) min(-1), r = 0.84) and %V(O(2)(max)) (80 +/
      12 versus 78 +/- 10%, r = 0.82). These results suggest that both VT and LT can
      be used to access AT in DM 2 women during graded treadmill exercise.

PMID- 16959366
TI  - Increased polymorphonuclear leukocyte respiratory burst function in type 2
      diabetes.
AB  - The predisposition to infection and chronic inflammation in diabetes may in part
      be related to the effects of hyperglycemia or other metabolic abnormality on
      polymorphonuclear leukocytes (PMN). We evaluated oxidative respiratory burst
      activity (superoxide production) in non-stimulated and stimulated PMN from 70
      stable type 2 Hispanic diabetic patients, as compared to 70 healthy Hispanic
      individuals without diabetes. The influences of protein kinase C (PKC) inhibitors
      and certain antibiotics on superoxide production were examined. Both resting and
      stimulated (PMA, zymosan) PMN from diabetic individuals produced more superoxide
      than PMN from controls. Inhibitors of PKC, a possible mediator of the augmented
      respiratory burst activity, decreased superoxide production in all (resting and
      stimulated) diabetic and control PMN. Azithromycin, which is markedly
      concentrated by PMN, profoundly inhibited superoxide generation in all groups of
      diabetic and control cells. PMN from Hispanic diabetic patients produced greater
      quantities of superoxide than non-diabetic controls. This increased oxidative
      respiratory burst activity may predispose to infection and chronic inflammation
      in diabetes. PKC inhibitors and azithromycin inhibited this respiratory burst
      response. The possible role of PKC (especially PKC beta) as the mediator of this
      augmented respiratory burst response requires further evaluation, and may lead to
      therapeutic studies with appropriate inhibitors.

PMID- 16959367
TI  - Adaptive evolution of tetrodotoxin resistance in animals.
AB  - Tetrodotoxin (TTX), first isolated from pufferfish (tetraodontids), is a highly
      potent neurotoxin that selectively binds to voltage-gated sodium channels (Na(v))
      in muscle and nerve tissues causing paralysis and death. Saxitoxin (STX) is a TTX
      related neurotoxin produced by dinoflagellates. Recent investigations have
      implicated diverse substitutions in the P-loop regions of skeletal muscle and
      neuronal Na(v) channels in the convergent evolution of neurotoxin resistance in
      pufferfish, garter snakes and softshell clams, which has enabled them to feed on
      TTX- and STX-bearing organisms.

PMID- 16959369
TI  - Extranodal marginal zone lymphoma of MALT involving the lungs, the stomach, and
      the colon.
AB  - Extranodal marginal zone lymphoma of MALT, previously known as MALT lymphoma, is
      a low grade B-cell Non-Hodgkin's lymphoma (NHL). Its most frequent locations are
      the gastrointestinal tract and the lungs while that of the colon is rare.
      Involvement of multiple mucosal sites is not a frequent finding but it does
      occur. We describe a case of a 70-year-old man who presented with extranodal
      marginal zone lymphoma of MALT involving three different sites: the lungs, the
      stomach, and the colon.

PMID- 16959370
TI  - Differential expression of STAT5 and Bcl-xL, and high expression of Neu and STAT3
      in non-small-cell lung carcinoma.
AB  - Experimental evidence suggests that in lung cancer, development, progression and
      an increased proliferation rate can be linked to apoptosis-related factors. The
      objective of this study is to evaluate the status of Neu, signal transducer and
      activator of transcription (STAT)-3, STAT5 and Bcl-xL expression in non-small
      cell lung cancer. We investigated the immunohistochemical expression of these
      proteins in 92 non-small-cell lung cancer specimens to establish their role in
      lung cancer pathogenesis. Neu was overexpressed in 65% of cases, and although
      STAT3 was overexpressed in 52.1% in cytoplasm, it was expressed in nucleus
      (activated) in 60.8%. Meanwhile, STAT5 was found overexpressed in 41.3% in
      cytoplasm and 32.6% in nucleus. Thus, Bcl-xL was overexpressed in cytoplasm in
      81.5%. Interestingly, we found nuclear expression of Bcl-xL in 30.4% of cases.
      Finally, we found correlation among histological types of lung cancer and nuclear
      expression of both STAT5 (P=0.005) and nuclear Bcl-xL (P=0.003). Besides, nuclear
      expression of Bcl-xL was correlated with TNM stage IV (distant metastasis)
      (P=0.02). These results suggest for the first time, a relevant role for STAT5 and
      Bcl-xL as apoptosis-regulatory proteins in the pathogenesis of lung cancer, and
      overexpression of both Neu and activated STAT3, could be related with the
      proliferation rate in lung carcinoma cells.

PMID- 16959371
TI  - Applied tracer tests in fractured rock: Can we predict natural gradient solute
      transport more accurately than fracture and matrix parameters?
AB  - Applied tracer tests provide a means to estimate aquifer parameters in fractured
      rock. The traditional approach to analysing these tests has been using a single
      fracture model to find the parameter values that generate the best fit to the
      measured breakthrough curve. In many cases, the ultimate aim is to predict solute
      transport under the natural gradient. Usually, no confidence limits are placed on
      parameter values and the impact of parameter errors on predictions of solute
      transport is not discussed. The assumption inherent in this approach is that the
      parameters determined under forced conditions will enable prediction of solute
      transport under the natural gradient. This paper considers the parameter and
      prediction uncertainty that might arise from analysis of breakthrough curves
      obtained from forced gradient applied tracer tests. By adding noise to an exact
      solution for transport in a single fracture in a porous matrix we create multiple
      realisations of an initial breakthrough curve. A least squares fitting routine is
      used to obtain a fit to each realisation, yielding a range of parameter values
      rather than a single set of absolute values. The suite of parameters is then used
      to make predictions of solute transport under lower hydraulic gradients and the
      uncertainty of estimated parameters and subsequent predictions of solute
      transport is compared. The results of this study show that predictions of
      breakthrough curve characteristics (first inflection point time, peak arrival
      time and peak concentration) for groundwater flow speeds with orders of magnitude
      smaller than that at which a test is conducted can sometimes be determined even
      more accurately than the fracture and matrix parameters.

PMID- 16959372
TI  - Limited contribution of claudin-5-dependent tight junction strands to endothelial
      barrier function.
AB  - Members of the claudin family are involved in formation of barriers that control
      access to the paracellular space of epithelia. Likewise, endothelium-specific
      claudin-5 is involved in the function of the blood-brain barrier (BBB). Here, we
      assessed the role of claudin-5 in non-BBB endothelial barriers using lentiviral
      driven overexpression and silencing of claudin-5 in its native environment of
      primary vascular endothelial cells. Effects were monitored using macromolecular
      tracers between 342Da and 40kDa. Measurements were made both in absence and
      presence of transmigrating leukocytes. Freeze-fracture preparations were analyzed
      for effects at the ultrastructural level. We show that overexpression of claudin
      5 leads to formation of elaborate networks of junction strands, which are absent
      in untransduced endothelial cells. Concomitantly, a modest, non-size-selective
      enhancement of the barrier function was observed. In contrast, silencing of
      endogenous claudin-5 does not influence barrier function. The efficient sealing
      of the endothelium during diapedesis of monocytes or granulocytes is also claudin
      5 independent. Collectively, these data provide evidence for a limited
      contribution of claudin-5 to the barrier function of human umbilical vein
      endothelial cells (HUVEC), implying that, unlike selective barriers in epithelia,
      the barrier of non-BBB endothelium seems largely independent of claudin-directed
      tight junction structures.

PMID- 16959373
TI  - How impulsiveness and variety influence food intake in a sample of healthy women.
AB  - This study investigates to what extent an impulsive personality, a varied food
      environment and their interaction influence food intake. We also investigated
      whether high-impulsives would exhibit more "eating disordered" thoughts and
      behaviours. Forty-five low-impulsives and forty-one high-impulsives did a bogus
      taste test with varied or monotonous food. As expected, high impulsives had a
      higher food intake compared to low impulsives. Moreover, high-impulsives reported
      significantly more "eating disordered" thoughts and behaviours than low
      impulsives. Neither a main effect of variety nor an interaction between variety
      and impulsivity were found.

PMID- 16959374
TI  - Anxiolytic-like effect of the selective neuropeptide Y Y2 receptor antagonist
      BIIE0246 in the elevated plus-maze.
AB  - The involvement of Neuropeptide Y (NPY) in the pathophysiology of mood disorders
      has been suggested by clinical and preclinical evidence. NPY Y1 and Y2 receptors
      have been proposed to mediate the NPY modulation of stress responses and anxiety
      related behaviors. To further investigate the role of Y2 receptors in anxiety we
      studied the effect of BIIE0246, a selective Y2 receptor antagonist, in the
      elevated plus-maze test. Rats treated with 1.0 nmol BIIE0246 showed an increase
      in the time spent on the open arm of the maze. In addition, to study the effects
      of the Y2 antagonism on NPY protein level, NPY-like immunoreactivity was measured
      in different brain regions following treatment with BIIE0246, but no
      statistically significant effects were observed. These results suggest that
      BIIE0246 has an anxiolytic-like profile in the elevated plus-maze.

PMID- 16959375
TI  - CRH inhibits NF-kappa B signaling in human melanocytes.
AB  - Corticotropin releasing hormone (CRH), a messenger of stress at the central
      level, is expressed in the epidermis where it operates within local equivalent of
      hypothalamo-pituitary axis. CRH inhibits NF-kappaB activity in human immortalized
      epidermal (PIG1) melanocytes. In melanocytes CRH stimulates pro-opiomelanocortin
      (POMC) mRNA and adrenocorticotropin (ACTH) peptide production. Knockdown of POMC
      levels by transfecting cells with antisense oligonucleotides blocks the effect of
      CRH on NF-kappaB signaling indicating that the above inhibition is indirect, e.g.
      through activation of POMC. We suggest that induction of POMC by CRH serves as a
      feedback mechanism to self-restrict inflammatory response in the skin.

PMID- 16959377
TI  - In vitro evidence for an antioxidant role of 3-hydroxykynurenine and 3
      hydroxyanthranilic acid in the brain.
AB  - We investigated the in vitro effect of 3-hydroxykynurenine (3HKyn), 3
      hydroxyanthranilic acid (3HAA), kynurenine (Kyn) and anthranilic acid (AA) on
      various parameters of oxidative stress in rat cerebral cortex and in cultured C6
      glioma cells. It was demonstrated that 3HKyn and 3HAA significantly reduced the
      thiobarbituric acid-reactive substances (TBA-RS) and chemiluminescence
      measurements in rat cerebral cortex, indicating that these metabolites prevent
      lipid peroxidation in the brain. In addition, GSH spontaneous oxidation was
      significantly prevented by 3HAA, but not by the other kynurenines in cerebral
      cortex. We also verified that 3HKyn and 3HAA significantly decreased the peroxyl
      radicals induced by the thermolysis of 2,2'-azo-bis-(2-amidinopropane)-derived
      peroxyl radicals, and to a higher degree than the classical peroxyl scavenger
      trolox. 2-Deoxy-d-ribose degradation was also significantly prevented by 3HKyn,
      implying that this metabolite was able to scavenge hydroxyl radicals.
      Furthermore, the total antioxidant reactivity of C6 glioma cells was
      significantly increased when these cells were exposed from 1 to 48h to 3HKyn,
      being the effect more prominent at shorter incubation times. TBA-RS values in C6
      cells were significantly reduced by 3HKyn when exposed from 1 to 6h with this
      kynurenine. However, C6 cell morphology was not altered by 3HKyn. Finally, we
      tested whether 3HKyn could prevent the increased free radical production induced
      by glutaric acid (GA), the major metabolite accumulating in glutaric acidemia
      type I, by evaluating the isolated and combined effects of these compounds on TBA
      RS levels and 2',7'-dihydrodichlorofluorescein (DCFH) oxidation in rat brain. GA
      provoked a significant increase of TBA-RS values and of DCFH oxidation, effects
      that were attenuated and fully prevented, respectively, by 3HKyn. The results
      strongly indicate that 3HKyn and 3HAA behave as antioxidants in cerebral cortex
      and C6 glioma cells from rats.

PMID- 16959376
TI  - Mapping convulsants' binding to the GABA-A receptor chloride ionophore: a
      proposed model for channel binding sites.
AB  - Gamma-aminobutyric acid (GABA) type A receptors play a key role in brain
      inhibitory neurotransmission, and are ligand-activated chloride channels blocked
      by numerous convulsant ligands. Here we summarize data on binding of picrotoxin,
      tetrazoles, beta-lactams, bicyclophosphates, butyrolactones and neurotoxic
      pesticides to GABA-A ionophore, and discuss functional and structural overlapping
      of their binding sites. The paper reviews data on convulsants' binding
      sensitivity to different point mutations in ionophore-lining second trans
      membrane domains of GABA-A subunits, and maps possible location of convulsants'
      sites within the chloride ionophore. We also discuss data on inhibition of
      glycine, glutamate, serotonin (5-HT3) and N-acetylcholine receptors by GABA-A
      channel blockers, and examine the applicability of this model to other homologous
      ionotropic receptors. Positioning various convulsant-binding sites within
      ionophore of GABA-A receptors, this model enables a better understanding of
      complex architectonics of ionotropic receptors, and may be used for developing
      new channel-modulating drugs.

PMID- 16959378
TI  - Reduced plasma membrane surface expression of GLAST mediates decreased glutamate
      regulation in the aged striatum.
AB  - Extracellular L-glutamate poses a severe excitotoxic threat to neurons and glia
      when unregulated, therefore low synaptic levels of this neurotransmitter must be
      maintained via a rapid and robust transport system. A recent study from our
      laboratory showed a reduced glutamate uptake rate in the striatum of the aged
      Fischer 344 (F344) rat, yet the mechanism underlying this phenomenon is unknown.
      The current study utilized in vivo electrochemical recordings, immunoblotting and
      biotinylation in young (6 months), late-middle aged (18 months) and aged (24
      months) F344 rats to elucidate the potential role that glutamate transporters
      (GLT-1, GLAST, and EAAC1) may play in this mechanism. Here we show that the time
      necessary to clear glutamate from the late-middle aged and aged striatum is
      significantly prolonged in comparison to the young striatum. In addition, an
      analysis of various sub-regions of the striatum revealed a marked dorsoventral
      gradient in terms of glutamate clearance times in the aged striatum, a phenomenon
      which was not present in the striatum of the animals of the remaining age groups.
      We also found that the decreased glutamate clearance time observed in the late
      middle aged and aged rats is not due to a decrease in the production of total
      transporter protein among these three transporters. Rather, a significant
      reduction in the amount of GLAST expressed on the plasma membrane surface in the
      aged animals (approximately 55% when compared to young rats) may contribute to
      this phenomenon. These age-related alterations in extracellular l-glutamate
      regulation may be key contributors to the increased susceptibility of the aged
      brain to excitotoxic insults such as stroke and hypoxia.

PMID- 16959379
TI  - Inflammatory processes in the aging mouse brain: participation of dendritic cells
      and T-cells.
AB  - Increased inflammatory activity accompanies normal brain aging. Whereas local
      glial cell activation, upregulation of cytokines and transcriptional alterations
      of inflammatory factors are well-documented components of this complex process,
      it is unclear whether blood-derived leukocytes also contribute to the age-related
      changes. The present study of normal mouse brain applied single and double
      immunohistochemistry to reveal for the first time that dendritic cells (DCs) and
      T-cells are important components of the general increased inflammatory state,
      which was documented by upregulation of reactive astrocytes and microglia. B
      cells and mast cells do not contribute to this inflammatory response. Dendritic
      cells and T-cells appeared at about 12 months of age and their number increased
      further during aging. In 24-month-old animals a dense network of DCs interspersed
      with T-cells pervaded brain areas where substantial histopathological changes and
      a volumetric decrease have been reported. All CD11c(+)-DCs displayed the typical
      dendritic shape and expressed the myeloid specific integrin CD11b. Some of the
      DCs were also CD205- or MIDC8-immunoreactive and expressed the cathepsins S and
      X. The emergence and prolonged presence of leukocytes might indicate a crucial
      role of these cells in local, age-related immune responses in the brain.

PMID- 16959380
TI  - [Neurosyphilis: a rare cause of dementia].
AB  - INTRODUCTION: Neurosyphilis had to be evoked in the face of an atypical dementia.
      CASE RECORD: We describe the case of a 65-year-old man who presented with
      neurosyphilis suspected to precede behavioral and cognitive problems in the
      context of risky sexual behavior and was confirmed by serologic tests in the
      cerebrospinal fluid. DISCUSSION: This case proves the necessity to investigate
      the possibility of neurosyphilis in subjects with dementia syndrome which does
      not correspond to classic etiologies.

PMID- 16959381
TI  - [Pyogenic psoas abscess: six cases and review of the literature].
AB  - PURPOSE: Psoas abscess is a rare disease in developed countries. Its diagnosis is
      difficult and any delay could lead to a worsen prognosis. The aim of this study
      is to determine the best diagnostic and therapeutic practices. METHODS: A
      retrospective study of psoas abscess that occurred during six months was
      performed. RESULTS: Six cases of secondary psoas abscess are reported. They were
      associated with spondylodiscitis in three cases, arthritis and gynaecologic
      infection in the three remaining cases. Anatomic diagnosis was performed by
      tomodensitometry. Microbiologic diagnosis was obtained by blood culture or direct
      puncture of the abscess. Antibiotics were associated with percutaneous drainage
      in two cases, with simple puncture in one case, and with surgery in one case. A
      local improvement w observed in all cases. The oldest patients presented the
      worst complications which were not directly caused by the abscess. CONCLUSION:
      Physicians must be aware of psoas abscess because of their increasing incidence.
      Despite the fact that digestive pathologies are the main cause of secondary psoas
      abscess, bone infections, particularly spine infections, should be taken into
      consideration. Tomodensitometry guided puncture or percutaneous drainage are of
      diagnostic and therapeutic interest. Infectious samples must be taken before
      starting antibiotics, which have to be efficient against Gram negative bacillus,
      anaerobes and Staphylococcus aureus. Surgery must be quickly performed when the
      primary infection localisation need it, in case of voluminous abscess or when
      antibiotics and drainage are inefficient.

PMID- 16959382
TI  - [Hepatosplenic localization of cat scratch disease: two cases in immunocompetent
      adult patients].
AB  - INTRODUCTION: Cat-Scratch Disease (CSD) is a well-recognized benign cause of
      localized lymphadenopathy, which often recovers spontaneously. However systemic
      clinical presentations are described in immunodeficient adults (bacillary
      angiomatosis, bacillary splenitis) and are less common in immunocompetent ones.
      EXEGESIS: We report two cases of disseminated CSD in immunocompetent patients,
      presenting hepatosplenic nodules, associated in the second case with an
      endocarditis. CONCLUSION: Bartonella serology must be achieved in case of
      hepatosplenic nodules with fever. Treatment of disseminated CSD in
      immunocompetent adults is still empirical and recovery can occur without
      antibiotherapy when endocarditis is not associated.

PMID- 16959383
TI  - The risk of disseminated Bacille Calmette-Guerin (BCG) disease in HIV-infected
      children.
AB  - OBJECTIVES: Bacille Calmette-Guerin (BCG), a live attenuated Mycobacterium bovis
      vaccine, poses a risk to human immunodeficiency virus (HIV)-infected children;
      this risk has not been well quantified. We estimate the risk of disseminated BCG
      disease in HIV-infected children in a setting highly endemic for tuberculosis and
      HIV. DESIGN AND METHODS: We conducted a prospective hospital-based surveillance
      study in the Western Cape Province, South Africa. Clinical and laboratory
      confirmed cases of disseminated BCG disease in children<1 year of age from
      January 2002 to December 2004 at a referral hospital were used as numerator data.
      Denominator data for calculations of disseminated BCG risk were obtained through
      estimating the total number of HIV-infected infants receiving BCG based on the
      known vaccination coverage in the study setting, combined with population data on
      the total number of children<1 year of age, the known HIV prevalence amongst
      women attending public antenatal care facilities and different scenarios (5-15%)
      for the rate of vertical HIV transmission. RESULTS: Nine cases of disseminated
      BCG disease were identified over the study period, seven of these were in HIV
      infected infants. The estimated risk for HIV-infected infants to develop
      disseminated BCG disease, given a 95% BCG coverage and an HIV prevalence of 12.4
      15.4% amongst women, were as follows for different scenarios of vertical HIV
      transmission: 329-417/100,000 vaccinees (assuming 5% vertical HIV transmission),
      164-208/100,000 vaccinees (assuming 10% vertical HIV transmission) and 110
      139/100,000 vaccinees (assuming 15% vertical HIV transmission). CONCLUSIONS: The
      risk of disseminated BCG disease is increased several hundred fold in HIV
      infected infants compared to the documented risk in HIV-uninfected infants. Data
      on the protective effect of BCG in HIV-exposed and infected children is lacking.
      Population- and hospital-based surveillance is vitally important to more
      accurately estimate the safety and benefits of BCG in HIV-exposed and infected
      infants.

PMID- 16959384
TI  - Study of the serological response after vaccination against tick-borne
      encephalitis in Sweden.
AB  - The antibody response to vaccination against tick-borne encephalitis (TBE) with
      FSME-Immun Inject (Immuno AG/Baxter) was studied in 535 persons, mainly adults,
      attending a vaccination centre in Stockholm, Sweden. Emphasis was laid on long
      term follow-up. Antibody activity was measured by three different serological
      test systems: a commercial ELISA kit, a hemagglutination inhibition (HI) test and
      a neutralization test (RFFIT). The neutralization test proved to be the most
      sensitive assay for the detection of the vaccine response, which was demonstrable
      in the majority of vaccinees (>90% after three and >98% after four and five
      vaccinations, respectively). ELISA and HI were less sensitive for antibody
      measurement during primary immunization. Neutralizing antibody activity persisted
      prior to the third dose in 77% of the vaccinees and prior to the fourth to sixth
      doses in 89-95% of the vaccinees. ELISA activity, but no neutralizing activity,
      was found in some individuals. Based on our data and previous experience of
      vaccine failures after two doses, a more condensed three-dose vaccination
      schedule may be advantageous and ought to be tested. The persistence of
      neutralizing antibodies justifies further studies of the antibody responses after
      the fourth dose for periods beyond the recommended 3-year booster intervals.

PMID- 16959385
TI  - An optimized vaccine vector based on recombinant vesicular stomatitis virus gives
      high-level, long-term protection against Yersinia pestis challenge.
AB  - We have developed recombinant vesicular stomatitis virus (VSV) vectors expressing
      the Yersinia pestis lcrV gene. These vectors, given intranasally to mice, induced
      high antibody titers to the LcrV protein and protected against intranasal
      (pulmonary) challenge with Y. pestis. High-level protection was dependent on
      using an optimized VSV vector that expressed high levels of the LcrV protein from
      an lcrV gene placed in the first position in the VSV genome, followed by a single
      boost. This VSV-based vaccine vector system has potential as a plague vaccine
      protecting against virulent strains lacking the F1 protein.

PMID- 16959386
TI  - Regression of Dupuytren's contracture following a cerebrovascular accident.

PMID- 16959387
TI  - Buck's direct repair of lumbar spondylolysis restores disc stresses at the
      involved and adjacent levels.
AB  - BACKGROUND: Lumbar spondylolysis was reported to cause disc degeneration at both
      caudal and cranial adjacent level. However, basic disc biomechanics in the
      spondylolytic spine is not fully understood. Purpose of this study was to analyze
      the disc stresses at cranial and caudal adjacent level of lumbar spondylolysis.
      Also, the biomechanical effects of Buck's technique on disc stresses at these two
      segments were evaluated. METHODS: An experimentally validated three-dimensional
      non-linear finite element model of the intact ligamentous L3-S1 segment was used.
      Bilateral lumbar spondylolysis was simulated by creating bilateral pars defects
      with 1.0 mm gap at L5. Buck's direct repair model was simulated with 4.0 mm
      cannulated Titanium screws, placed bilaterally across the defect. Von Mises
      stresses in the annulus fibrosus and nucleus pulposus at L4/5 (cranial adjacent)
      and L5/S (caudal adjacent) disc levels were analyzed in flexion, extension,
      lateral bending and axial rotation in response to 400 N of axial compression and
      10.6 Nm moment. The highest values were compared among the three models, intact,
      spondylolysis and Buck's technique. FINDINGS: After spondylolysis occurred at L5,
      annulus fibrosus and nucleus pulposus stresses at L4/5 increased to 111% and
      120%, respectively. After the Buck's technique it recovered to 102% and 105%,
      correspondingly. On the other hand, at L5/S, annulus fibrosus stress increased to
      168%, and nucleus pulposus, 155%, which was much higher when compared to the
      stresses at L4/5. After the Buck's technique the stresses were decreased to 125%
      and 120%, correspondingly. During rotation motion, especially, the operation
      normalized the disc stress completely. INTERPRETATION: Spondylolysis increases
      disc stresses at the affected as well as cranial adjacent level, and it may lead
      to disc degeneration at both levels. However, the increase in stresses is higher
      at the affected caudal level, when compared to the cranial level. Buck's
      technique may restore the disc stresses back to normal at both disc levels. Thus,
      this technique may be beneficial from a biomechanical perspective as well.

PMID- 16959388
TI  - Increasing bending strength of tibial locking screws: mechanical tests and finite
      element analyses.
AB  - BACKGROUND: Healing of tibial fractures treated by locked nailing is threatened
      by locking screw failure. However, the effects of the design factors of the
      screws on their mechanical strength have rarely been studied. METHOD: Three-point
      bending tests and finite element analyses were used to investigate the bending
      strength of five types of commercially available tibial locking screws and two
      types of specially designed screws. Yielding strength and fatigue life measured
      in bending tests were correlated to total strain energy and maximal tensile
      stress computed in finite element analyses. Parametric analysis and design
      optimization were done according to the Taguchi method. Validation studies to
      assess the stress rising effect of the threads on the fatigue strength were
      conducted in two types of new screws made of either stainless steel or titanium
      alloy. FINDINGS: The yielding strength of the screws was closely related to their
      total strain energy, and the logarithm of the fatigue life was closely related to
      the maximal tensile stress with correlation coefficients of -0.95 and -0.90,
      respectively. Parametric studies indicated that fatigue strength of the screws
      was affected mainly by inner diameter (contribution, 63.8%) and root radius
      (27.8%). The yielding strength was determined primarily by inner diameter
      (88.5%). Titanium screws had a longer fatigue life than stainless steel screws,
      especially in screws with larger root radii. INTERPRETATION: A screw's strength
      is closely related to its design factors. Finite element models, which can
      reliably reflect the mechanical strength of screws can save time and effort
      during screw design. Larger root radius can effectively improve the fatigue
      strength, especially for titanium screws as compared with stainless steel screws.

PMID- 16959389
TI  - Contraceptive practices in Armenia: Panel evaluation of an Information-Education
      Communication Campaign.
AB  - Induced abortion remains the major form of birth control among Armenian women,
      contributing to their excess mortality and preventable morbidity. Reliance on
      abortion is attributed to limited access to information concerning modern methods
      of contraception and to widely held misinformation among women regarding family
      planning and reproductive health. Based on the Steps to Behavior Change model,
      the Green Path Campaign for Family Health, an information-education-communication
      (IEC) campaign, was launched in June 2000. This multimedia campaign promoted
      greater awareness, knowledge, acceptance, and adoption of modern contraception
      through increased utilization of counseling and related services provided at
      underutilized family planning centers. A representative panel of 1088 married
      women aged 18-35 were surveyed on reproductive health/family planning knowledge,
      attitudes, and practices immediately prior to and immediately following the 6
      month national campaign. Exposure to the campaign was associated with significant
      increases in factors associated with contraceptive behavior change: knowledge,
      favorable attitudes toward modern methods, favorable attitudes toward family
      planning services, and information seeking and utilization of family planning
      services. Women who were more educated, more affluent, and slightly older were
      more likely to use family planning services as well as modern contraceptive
      methods. New visits to family planning centers increased by 84%. Despite the
      usual 25% turnover among those using modern methods at the start of the study,
      use of modern contraceptive methods increased by 4.6%, significantly exceeding
      the projected 3% increase. The results document changes in underlying behavioral
      predictors consistent with the Steps to Behavior Change model and highlight the
      relatively untapped potential of media-based health promotion efforts in post
      Soviet Republics.

PMID- 16959390
TI  - Determinants for the adoption of angiotensin II receptor blockers by general
      practitioners.
AB  - Results of studies conducted 10-20 years ago show the prominence of commercial
      information sources in the adoption process of new drugs. Over the past decade,
      there has been a growing emphasis on practicing evidence-based medicine in drug
      prescribing. This raises the question whether professional information sources
      currently counterbalance the influence of commercial information sources in the
      adoption process. The aim of this study was to identify determinants influencing
      the adoption of a new drug class, the angiotensin II receptor blockers (ARBs), by
      general practitioners (GPs) in The Netherlands. A retrospective study was
      conducted to assess prevalent ARB prescribing for hypertensive patients using the
      Integrated Primary Care Information (IPCI) database. We conducted a survey among
      all GPs who participated in the IPCI project in 2003 to assess their exposure to
      commercial and professional information sources, perceived benefits and risks of
      ARBs, perceived influences of the professional network, and general
      characteristics. Multilevel logistic regression was applied to identify
      determinants of ARB adoption while adjusting for patient characteristics. Data
      were obtained from 70 GPs and 9470 treated hypertensive patients. A total of 1093
      patients received ARBs (12%). GPs who reported frequent use of commercial
      information sources were more likely to prescribe ARBs routinely in preference to
      other antihypertensives, whereas GPs who used a prescribing decision support
      system and those who were involved in pharmacotherapy education were less likely
      to prescribe ARBs. Other factors that were associated with higher levels of ARB
      adoption included a more positive perception of ARBs regarding their
      effectiveness in lowering blood pressure, and working in single-handed practices
      or in rural areas. Aside from determinants related to the patient population,
      adoption of a new drug class among Dutch GPs is still determined more by their
      reliance on promotional information than by their use of professional information
      sources.

PMID- 16959391
TI  - Cigarette smoking and poverty in China.
AB  - Drawing on the 1998 China national health services survey data, this study
      estimated the poverty impact of two smoking-related expenses: excessive medical
      spending attributable to smoking and direct spending on cigarettes. The excessive
      medical spending attributable to smoking is estimated using a regression model of
      medical expenditure with smoking status (current smoker, former smoker, never
      smoker) as part of the explanatory variables, controlling for people's
      demographic and socioeconomic characteristics. The poverty impact is measured by
      the changes in the poverty head count, after smoking-related expenses are
      subtracted from income. We found that the excessive medical spending attributable
      to smoking may have caused the poverty rate to increase by 1.5% for the urban
      population and by 0.7% for the rural population. To a greater magnitude, the
      poverty headcount in urban and rural areas increased by 6.4% and 1.9%,
      respectively, due to the direct household spending on cigarettes. Combined, the
      excessive medical spending attributable to smoking and consumption spending on
      cigarettes are estimated to be responsible for impoverishing 30.5 million urban
      residents and 23.7 million rural residents in China. Smoking related expenses
      pushed a significant proportion of low-income families into poverty in China.
      Therefore, reducing the smoking rate appears to be not only a public health
      strategy, but also a poverty reduction strategy.

PMID- 16959392
TI  - Managing competition in the countryside: Non-profit and for-profit perceptions of
      long-term care in rural Ontario.
AB  - This paper contributes to the current debates surrounding private delivery of
      health care services by addressing the distinctive challenges, constraints and
      opportunities facing for-profit and non-profit providers of long-term care in
      rural and small town settings. It focuses on the empirical case of Ontario,
      Canada where extensive restructuring of long-term care, under the rubric of
      managed competition, has been underway since the mid-1990s. In-depth interviews
      with 72 representatives from local governments, public health institutions and
      authorities, for-profit and non-profit organisations, and community groups during
      July 2003 to December 2003 form the platform for a qualitative analysis of the
      implications of managed competition as it relates to the provision of long-term
      care in the countryside. The results suggest that the introduction and
      implementation of managed competition has accentuated the problems of service
      provision in rural communities, and that the long-standing issues of caregiving
      in rural situations transcend the differences, perceived or otherwise, between
      for-profit and non-profit provision. Understanding the implications of market
      oriented long-term care restructuring initiatives for providers, and their
      clients, in rural situations requires a re-focussing of research beyond the for-
      versus non-profit dichotomy.

PMID- 16959393
TI  - Changes in LORETA and conventional patterns of P600 after steroid treatment in
      multiple sclerosis patients.
AB  - OBJECTIVE: The P600 component of event-related potentials (ERPs) reflecting the
      'rule-governed sequence of information processing', has been associated with
      multiple sclerosis (MS)-related cognition. The present study aimed at examining
      the effects of methylprednisolone treatment in MS patients on cognition as
      reflected by the low-resolution brain electromagnetic tomography (LORETA) of the
      P600 as well as its conventional constituents (amplitudes and latencies) recorded
      during a working memory (WM) test. METHOD: A paired LORETA comparison was
      performed in the P600 component of ERPs elicited during a (WM) test in 18 MS
      patients suffering from the relapsing-remitting form, before and after 1 week
      treatment with methylprednisolone. The P600 component was also evaluated in 16
      healthy controls matched to the patients on age and educational level. RESULTS:
      When pre- and post-treatment recordings of LORETA were compared all patients as a
      group showed significantly different patterns of current density activation
      located at right frontal lobe. The treatment was accompanied by an increase of
      the amplitude of P600 at the right frontoparietal area. In the post-treatment
      phase the patients exhibited significant improvement of the memory performance as
      compared to themselves before treatment. As a result both the P600 amplitudes and
      memory performance at post-treatment were closer to those exhibited by normal
      controls. CONCLUSION: These findings support the notion that steroid treatment in
      relapsing-remitting MS patients, may exert a beneficial effect in 'rule-governed
      sequence of information processing'.

PMID- 16959394
TI  - Rex3 (reduced in expression 3) as a new tumor marker in mouse
      hepatocarcinogenesis.
AB  - In a previous microarray expression analysis, Rex3, a gene formerly not linked to
      tumor formation, was found to be highly overexpressed in both Ctnnb1-(beta
      Catenin) and Ha-ras-mutated mouse liver tumors. Subsequent analyses by in situ
      hybridization and real-time PCR confirmed a general liver tumor-specific
      overexpression of the gene (up to 400-fold). To investigate the role of Rex3 in
      liver tumors, hepatoma cells were transfected with FLAG- and Myc-tagged Rex3
      expression vectors. Rex3 was shown to be exclusively localized to the cytoplasm,
      as determined by fluorescence microscopy and Western blotting. However, forced
      overexpression of Rex3 did not significantly affect proliferation or stress
      induced apoptosis of transfected mouse hepatoma cells. Rex3 mRNA was determined
      in primary hepatocytes in culture by real-time PCR. In primary mouse hepatocytes,
      expression of Rex3 increased while cells dedifferentiated in culture. This effect
      was abolished when hepatocytes were maintained in a differentiated state.
      Furthermore, expression of Rex3 decreased in mouse liver with age of mice and the
      expression profile was highly correlated to that of the tumor markers alpha
      fetoprotein and H19. The findings suggest a role of Rex3 as a marker for
      hepatocyte differentiation/dedifferentiation processes and tumor formation.

PMID- 16959395
TI  - Localization of cytochrome P450 1A1 in a specific region of hydronephrotic kidney
      of rat neonates lactationally exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - Hydronephrosis is typically observed in terata caused by in utero and lactational
      exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), via the arylhydrocarbon
      receptor, but the molecular mechanism underlying its pathogenesis is largely
      unknown. In the present study, pregnant Holtzman rats were treated once by gavage
      with TCDD (1.0 microg/kg bw) or corn oil on gestation day 15. All dams were
      allowed to litter, and standardized litters in terms of litter size were then
      reciprocally cross-fostered on postnatal day (PND) 1. On PND1, pups were divided
      into four experimental groups: pups exposed only in utero, pups exposed only
      lactationally, pups not exposed via either route (vehicle control), and pups
      exposed via both routes. Pups were euthanized on PND21 for further analyses. The
      TCDD dose used was not overtly toxic to the dams or neonates. The incidence and
      severity of hydronephrosis were markedly high in pups exposed to TCDD
      lactationally, but not those exposed in utero. On PND21, cytochrome P450 (CYP)
      1A1 was detected predominantly in the outer zone of the medulla of the kidney
      from all the pups lactationally exposed to TCDD, regardless of the occurrence of
      hydronephrosis. Interestingly, TCDD concentrations in the cortex, the outer zone
      of the medulla and the inner zone of the medulla were similar. When adult
      Holtzman rats were administered TCDD, the induction of CYP1A1 was
      immunohistochemically detected in the liver but not in the kidney 7 days
      postadministration. The present findings suggest that TCDD-inducible genes via an
      AhR-dependent mechanism may be associated with the etiology of hydronephrosis in
      a particular region of the kidney.

PMID- 16959396
TI  - The thief process for mercury removal from flue gas.
AB  - The Thief Process is a cost-effective variation to activated carbon injection
      (ACI) for removal of mercury from flue gas. In this scheme, partially combusted
      coal from the furnace of a pulverized coal power generation plant is extracted by
      a lance and then re-injected into the ductwork downstream of the air preheater.
      Recent results on a 500-lb/h pilot-scale combustion facility show similar
      removals of mercury for both the Thief Process and ACI. The tests conducted to
      date at laboratory, bench, and pilot-scales demonstrate that the Thief sorbents
      exhibit capacities for mercury from flue gas streams that are comparable to those
      exhibited by commercially available activated carbons. A patent for the process
      was issued in February 2003. The Thief sorbents are cheaper than commercially
      available activated carbons; exhibit excellent capacities for mercury; and the
      overall process holds great potential for reducing the cost of mercury removal
      from flue gas. The Thief Process was licensed to Mobotec USA, Inc. in May of
      2005.

PMID- 16959397
TI  - Long-term dynamics in land resource use and the driving forces in the Beressa
      watershed, highlands of Ethiopia.
AB  - Land degradation in the Ethiopian highlands is considered to be one of the major
      problems threatening agricultural development and food security in the country.
      However, knowledge about the forces driving the long-term dynamics in land
      resources use is limited. This research integrates biophysical information with
      socio-economic processes and policy changes to examine the dynamics of land
      resource use and farmers' livelihoods in the Beressa watershed for over 40 years
      during the second half of the 20th century. It was found that there have been
      substantial dynamics in land resource use in the area. The natural vegetation
      cover has been extensively cleared, although most of the cleared areas have since
      been replaced with plantations. Grazing land has expanded remarkably at the
      expense of cropland and bare land. However, the expansion of cropland was minimal
      over the 43-year period despite a quadrupling of the population density. Yields
      have not increased to compensate for the reduction in per capita cropland, and
      the soil quality appears to be not that good. Though the farmers perceived it
      otherwise, the long-term rainfall pattern has improved. In response to soil
      degradation, water shortage, socio-economic and policy changes, farmers have
      tended to gradually change from annual cropping to tree planting and livestock
      production to cope with the problems of soil degradation, water scarcity and
      smaller farms. Income diversification through the sale of wood and cattle dung is
      becoming a major livelihood strategy. Apparently, however, little attention has
      been paid to investments in soil and water conservation (SWC) and local soil
      fertility amendments. In particular, increased erosion and related high nutrient
      losses in sediments, as well as the removal of potentially available soil
      nutrients through the sale of manure threatens to damage agricultural
      sustainability in the area.

PMID- 16959398
TI  - Prosthetic nephrovesical bypass.

PMID- 16959399
TI  - Complications and other surgical outcomes associated with extended pelvic
      lymphadenectomy in men with localized prostate cancer.
AB  - OBJECTIVES: More-extensive pelvic lymph node dissection (PLND) may be associated
      with a higher rate of complications and a longer hospital stay than more limited
      PLND. METHODS: Before radical retropubic prostatectomy, PLNDs were performed in
      963 patients. Of these, 767 (79.6%) had >or=10 lymph nodes removed and examined
      (extended PLND [ePLND]), while 1-9 nodes (limited PLND [lPLND]) were removed in
      the remaining 196 (20.4%). Limits included external iliac, obturator, internal
      iliac, and iliac bifurcation. PLND-related complications and the length of
      hospital stay were recorded prospectively and analyzed according to the extent of
      PLND. RESULTS: In patients subjected to ePLND, the overall rate of complications
      was 19.8% versus 8.2% in those treated with lPLND (p<0.001). In individual
      analyses of specific complications, only the lymphocele rate was significantly
      higher after ePLND (10.3% vs 4.6%; p=0.01). Similarly, ePLND translated into a
      longer hospital stay (9.9 vs 8.2 d; p<0.001). These differences persisted when
      adjustment was made for prostate-specific antigen and either clinical or
      pathologic tumor characteristics. CONCLUSIONS: Our data indicate that, even in
      the hands of experienced urologic surgeons, ePLNDs are associated with higher
      complication rates and longer hospital stay. These detriments need to be taken
      into account when the staging benefit associated with ePLND is considered.

PMID- 16959401
TI  - Civilization as a biosystem examined by the comparative analysis of biosystems.
AB  - Darwinian evolutionary theory has played a central role in the life sciences.
      However, this principle is rarely applied to exceptional life-like systems such
      as human societies and the life-like chemical systems associated with the origin
      of life. For a description of the nature of these exceptional life-like
      biosystems, the development of alternative approaches is necessary. The existence
      of analogies among biosystems at different hierarchical levels has frequently
      been discussed. The present paper, however, focuses on the analogies of the
      structures and functions of different biosystems, based on the following
      perspectives. The roles of an individual biosystem and its building blocks in
      relation to the environment are evaluated from the standpoint of the hierarchies
      of organisms, whereby the principle of which hierarchy is regarded as an
      "individual" biosystem is proposed. In addition, the definition and
      characteristics of civilization are discussed on the basis of this principle. The
      analogies between cell-type systems, civilizations, ecosystems, and other
      biosystems are qualitatively evaluated. It is reasonable to regard all biosystems
      as possessing clear or ambiguous boundaries. Biosystems at higher levels than
      prokaryotes comprise both living and non-living building blocks, while
      prokaryotes comprise only non-living building blocks. The similarities concerning
      the interactions among the building blocks in relation to their environment are
      also discussed. Furthermore, the analogy between different biosystems concerning
      metabolism, self-reproduction, mutation, the relationship between genotype and
      phenotype (information and function), individuality, and stability are evaluated.
      The proposed analytical approach not only provides an insight into the
      characteristics of civilizations as biosystems, but also the characteristics of
      biosystems at different hierarchical levels.

PMID- 16959402
TI  - Dopamine D(2) receptor expression and regulation of gonadotropin alpha-subunit
      gene in clonal gonadotroph LbetaT2 cells.
AB  - This study investigated the role of dopamine on the regulation of gonadotropin
      secretion at the gonadotroph cell line. We examined the function of the dopamine
      D(2) receptor in the regulation of pituitary gonadotropin gene expression using
      LbetaT2 cells, a mature, well differentiated clonal gonadotroph cell line. The
      presence of the dopamine D(2) receptor in the LbetaT2 cells was confirmed by both
      RT-PCR and Western blot. Gonadotropin releasing hormone (GnRH) stimulation
      resulted in gonadotropin LHbeta, FSHbeta and alpha-subunit promoter activation,
      and none were inhibited by quinpirol, a specific dopamine D(2) receptor agonist.
      Pituitary adenylate cyclase-activating polypeptide (PACAP) increased gonadotropin
      alpha-subunit promoter activity, but not LHbeta and FSHbeta promoter activity.
      The activity of PACAP was significantly inhibited in the presence of quinpirol.
      The protein kinase A inhibitor, H89, also inhibited PACAP-induced alpha-subunit
      gene expression. PACAP increased intracellular cAMP more than GnRH did in LbetaT2
      cells, and the elevation of cAMP was strongly inhibited in the presence of
      various dopamine D(2) agonists. These results suggest that in pituitary
      gonadotrophs, the dopamine D(2) receptor is a negative regulator of gonadotropin
      alpha-subunit gene expression which is induced by cAMP-elevating factors in a
      cAMP-dependent pathway.

PMID- 16959404
TI  - Coagulation/flocculation process and sludge conditioning in beverage industrial
      wastewater treatment.
AB  - Attempts were made in this study to examine the effectiveness of coagulation and
      flocculation process using ferric chloride and polyelectrolyte (non-ionic
      polyacrylamide) for the treatment of beverage industrial wastewater. Removal of
      organic matter (expressed as chemical oxygen demand, COD), total phosphorus (TP)
      and total suspended solid (TSS) using ferric chloride and organic polyelectrolyte
      during coagulation/flocculation process were investigated. Also, the optimum
      conditions for coagulation/flocculation process, such as coagulant dosage,
      polyelectrolyte dosage, and pH of solution were investigated using jar-test
      experiment. The effect of different dosages of polyelectrolyte in combination
      with coagulant was also studied. The results revealed that in the range of pH
      tested, the optimal operating pH was 9. Percentage removals of 73, 95 and 97 for
      COD, TP and TSS, respectively, were achieved by the addition of 300mg/L
      FeCl(3).6H(2)O, whereas 91, 99 and 97% removal of COD, TP and TSS, respectively,
      were achieved with the addition of 25mg/L polyelectrolyte to 100mg/L ferric
      chloride. The volume of sludge produced, when ferric chloride was used solely,
      was higher compared to the use of combination of polyelectrolyte and
      FeCl(3).6H(2)0. The combined use of coagulant and polyelectrolyte resulted in the
      production of sludge volume with reduction of 60% of the amount produced, when
      coagulant was solely used for the treatment. It can be concluded from this study
      that coagulation/flocculation may be a useful pre-treatment process for beverage
      industrial wastewater prior to biological treatment.

PMID- 16959403
TI  - Down-regulation of survivin by ultraviolet C radiation is dependent on p53 and
      results in G(2)-M arrest in A549 cells.
AB  - Deregulation of survivin expression is implicated in tumorigenesis. To examine
      the regulation of survivin expression in response to DNA damage, we exposed A549
      human lung cancer cells to ultraviolet C (UVC) radiation, which induces DNA
      single-strand breakage. UVC irradiation induced G(2)-M arrest that was
      accompanied by accumulation of p53 and subsequent down-regulation of survivin.
      Depletion of p53 by RNA interference prevented the UVC-induced down-regulation of
      survivin. Furthermore, depletion of survivin resulted in G(2)-M arrest,
      suggesting that down-regulation of survivin by p53 contributes to the p53
      dependent G(2)-M checkpoint triggered by DNA damage.

PMID- 16959405
TI  - Assessment of alternative management techniques of tank bottom petroleum sludge
      in Oman.
AB  - This paper investigated several options for environmentally acceptable management
      techniques of tank bottom oily sludge. In particular, we tested the applicability
      of managing the sludge by three options: (1) as a fuel supplement; (2) in
      solidification; (3) as a road material. Environmental testing included
      determination of heavy metals concentration; toxic organics concentration and
      radiological properties. The assessment of tank bottom sludge as a fuel
      supplement included various properties such as proximate analysis, ultimate
      analysis and energy content. Solidified sludge mixtures and road application
      sludge mixtures were subjected to leaching using the toxicity characteristic
      leaching procedure (TCLP). Tank bottom sludge was characterized as having higher
      concentrations of lead, zinc, and mercury, but lower concentrations of nickel,
      copper and chromium in comparison with values reported in the literature. Natural
      occurring radioactive minerals (NORM) activity values obtained on different
      sludge samples were very low or negligible compared to a NORM standard value of
      100Bq/g. The fuel assessment results indicate that the heating values, the carbon
      content and the ash content of the sludge samples are comparable with bituminous
      coal, sewage sludge, meat and bone meal and petroleum coke/coal mixture, but
      lower than those in car tyres and petroleum coke. The nitrogen content is lower
      than those fuels mentioned above, while the sulfur content seems comparable with
      bituminous coal, petroleum coke and a petroleum coke/coal mixture. The apparent
      lack of leachability of metals from solidification and road material sludge
      applications suggests that toxic metals and organics introduced to these
      applications are not readily attacked by weak acid solutions and would not be
      expected to migrate or dissolved into the water. Thus, in-terms of trace metals
      and organics, the suggested sludge applications would not be considered hazardous
      as defined by the TCLP leaching procedure.

PMID- 16959406
TI  - Effects of mixed surfactants on the volatilization of naphthalene from aqueous
      solutions.
AB  - The effects of mixed anionic-nonionic surfactants, Tween40-SDS (sodium dodecyl
      sulfate), Tween40-SDBS (sodium dodecylbenzene sulfonate), Tween20-SDS and Tween20
      SDBS, on the solubility and volatilization of naphthalene from static aqueous
      solutions were investigated. The experiment results indicated that mixed anionic
      nonionic surfactants can solubilize naphthalene synergistically, which was
      resulted from the reduction in critical micelle concentration (CMC) of the mixed
      surfactant and the increase in micellar partition coefficient (K(mc)) of
      naphthalene between micelles and aqueous phase. The synergistic effects of mixed
      surfactants resulted in further reduction in volatilization of naphthalene than
      that induced by single surfactant. A positive linear correlation was found
      between the synergistic solubilization ratio (DeltaS) and the synergistic
      inhibitory capacity on naphthalene volatilization (DeltaC) in the presence of
      mixed surfactants. Results from this study imply that mixed surfactants can be
      employed in environmental remediation to formulate the needed solubility and
      volatilization of volatile and semivolatile compounds in aqueous solutions.

PMID- 16959407
TI  - An on-line pre-concentration system for determination of cadmium in drinking
      water using FAAS.
AB  - In the present paper, a minicolumn of polyurethane foam loaded with 4-(2
      pyridylazo)-resorcinol (PAR) is proposed as pre-concentration system for cadmium
      determination in drinking water samples by flame atomic absorption spectrometry.
      The optimization step was performed using two-level full factorial design and
      Doehlert matrix, involving the variables: sampling flow rate, elution
      concentration, buffer concentration and pH. Using the established experimental
      conditions in the optimization step of: pH 8.2, sampling flow rate 8.5 mL min(
      1), buffer concentration 0.05 mol L(-1) and elution concentration of 1.0 mol L(
      1), this system allows the determination of cadmium with detection limit (LD)
      (3sigma/S) of 20.0 ng L(-1) and quantification limit (LQ) (10sigma/S) of 64 ng L(
      1), precision expressed as relative standard deviation (R.S.D.) of 5.0 and 4.7%
      for cadmium concentration of 5.0 and 40.0 microg L(-1), respectively, and a pre
      concentration factor of 158 for a sample volume of 20.0 mL. The accuracy was
      confirmed by cadmium determination in the standard reference material, NIST SRM
      1643d trace elements in natural water. This procedure was applied for cadmium
      determination in drinking water samples collected from Salvador City, Bahia,
      Brazil. For five samples analyzed, the achieved concentrations varied from 0.31
      to 0.86 microg L(-1).

PMID- 16959408
TI  - TiO2 mediated photocatalytic degradation studies of Reactive Red 198 by UV
      irradiation.
AB  - Photocatalytic degradation of an aqueous solution of azo dye (Reactive Red 198)
      used in textile industries by UV irradiation was investigated. The effect of
      initial dye concentration, TiO(2) loading, pH and H(2)O(2) on degradation rate
      was ascertained and optimized conditions for maximum degradation were determined.
      The kinetics of photocatalytic degradation was found to follow a pseudo-first
      order according to Langmuir-Hinshelwood model. The degradation experiment under
      optimized reaction conditions was investigated under sunlight.

PMID- 16959409
TI  - Detonation velocity of pure and mixed CHNO explosives at maximum nominal density.
AB  - In this paper, a simple approach is introduced to predict detonation velocity of
      pure and mixed explosives at maximum nominal density. This technique may be
      applied to any pure or mixed explosives that contain elements of carbon,
      hydrogen, nitrogen and oxygen. The new method requires only elemental composition
      and some specific structural parameters. The introduced correlation can easily be
      applied for determining maximum expected detonation velocity of any new CHNO
      explosive without using its crystal density. Calculated detonation velocities by
      this procedure for both pure and composite explosive formulations show good
      agreement with respect to measured detonation velocity at maximum nominal
      density.

PMID- 16959410
TI  - Neuromodulatory effect of bromazepam on motor learning: an
      electroencephalographic approach.
AB  - To investigate the effects of bromazepam on motor performance and
      electroencephalographic activity (qEEG) in healthy subjects, during the process
      of learning a typewriting task, with a focused attention demand. A randomized
      double-blind model was used to allocate subjects in one of the following
      conditions: placebo (n=13), bromazepam 3 mg (n=13) or bromazepam 6 mg (n=13).
      Forty minutes after treatment administration, subjects were submitted to the
      motor task. EEG activity was recorded simultaneously. The analyzed variables
      were: number of errors and execution time, which were extracted from each block
      of the typewriting task, and mean relative power values in the beta band (13-35
      Hz), extracted from the qEEG. A significantly lower number of typing errors was
      observed in both bromazepam conditions (Br 3 mg and Br 6 mg) when compared to the
      placebo. There was no difference between the two bromazepam conditions. For the
      execution time variable, a better performance was observed in the Br 3 mg
      condition, but with no statistical significance. The highest degree of cortical
      activation during the task was observed in Br 3 mg and Br 6 mg when compared to
      placebo. The medication's anxiolytic effect intensifies the attentional focus
      over predictable events occurring in reduced perceptual fields. The qEEG's
      accentuated response in pre-motor and primary motor areas suggests a greater
      effort directed to the most relevant aspects of the task. In short, the doses
      employed (3 and 6 mg) seem to enhance the learning of motor tasks that involve
      focused attention, such as typewriting.

PMID- 16959412
TI  - Material-independent cerebral network of re-experiencing personal events:
      evidence from two parallel fMRI experiments.
AB  - Two parallel fMRI experiments were conducted with the aim to clarify the
      lateralisation issue of the cerebral network underlying autobiographical memory
      retrieval independently of the stimulus material and the refreshment of the
      memory trace. The verbal experiment required a pre-scanning interview, while the
      nonverbal version tested the subjects directly during the fMRI session. Both
      experiments were constructed using the same experimental design to eliminate
      methodological variables in order to render comparisons possible. We found a
      predominantly left-lateralised cerebral network independently of material and
      regardless of whether or not memory traces were reactivated prior to the scanning
      session. We discuss the results in the context of neuroimaging studies of
      autobiographical memory (AbM).

PMID- 16959411
TI  - Evaluation of clinically relevant glutamate pathway inhibitors in in vitro model
      of Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal dominant, inherited and fatal
      neurodegenerative disorder for which there is, at present, no effective treatment
      or cure. Striatal medium spiny neurons (MSN) are the most sensitive in HD.
      Dysregulation of glutamate/calcium signaling pathway emerges as a possible cause
      of striatal MSN neurodegeneration in HD. Here we evaluated five clinically
      relevant glutamate pathway inhibitors using previously developed in vitro HD
      model. We found that folic acid, gabapentin and lamotrigine did not protect HD
      neurons from glutamate-induced cell death, but memantine and riluzole were
      protective. Our results provide further support to potential use of memantine and
      riluzole for treatment of HD.

PMID- 16959413
TI  - Effects of neonatal capsaicin treatment in the neutrophil production, and
      expression of preprotachykinin-I and tachykinin receptors in the rat bone marrow.
AB  - Bone marrow is richly innervated with both myelinated and non-myelinated nerve
      fibers, but the role of this innervation on hemopoiesis is poorly understood.
      Therefore, the aim of this study was to investigate the role of C-fibers on
      hematopoiesis. Wistar rats were neonatally injected with either capsaicin or its
      vehicle, and used at adult ages (8-10 weeks). In capsaicin-pretreated rats, the
      levels of substance P (SP) in bone marrow fluid were markedly reduced in
      comparison with the vehicle group (13.1+/-4.5 pg/ml versus 47.3+/-5.5 pg/ml,
      p<0.05). In bone marrow, the number of total leukocytes was 28% higher (p<0.05)
      in capsaicin-pretreated group, and this accompanied by a higher number of
      neutrophils, particularly of the immature forms. The mononuclear cell and
      eosinophils counts did not differ significantly among vehicle and capsaicin
      groups. In peripheral blood, the number of circulating neutrophils in the
      capsaicin group increased by 53.8% (p<0.05), whereas the number of mononuclear
      cells did not change significantly among groups. Eosinophils were virtually
      absent in the circulating blood in both groups. Semi-quantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) showed that both
      preprotachykinin (PPT)-I mRNA and the tachykinin neurokinin (NK)-1 mRNA
      expression in bone marrow cells significantly increased in capsaicin group,
      whereas the NK-2 mRNA expression was unchanged after capsaicin pretreatment. In
      conclusion, our data show that chronic neuropeptide depletion enhance the
      neutrophil proliferation and differentiation in the rat bone marrow by mechanisms
      involving upregulation of PPT-I gene and NK-1 receptors.

PMID- 16959414
TI  - Improvement of focal ischemia-induced rat dopaminergic dysfunction by striatal
      transplantation of mouse embryonic stem cells.
AB  - Middle cerebral artery occlusion (MCAO) caused behavioral dysfunction with
      massive neuronal loss. Cell transplantation may recover this deficit by replacing
      damaged brain cells. In this study, we examined the effects of transplantation of
      mouse embryonic stem (ES) cells or ES cell-derived neuron-like (ES-N) cells on
      behavioral function in ischemic rats. Seven days after MCAO, ES or ES-N cells
      were transplanted into ipsilateral striata (but not the substantia nigra) of
      ischemic rats. Transplanted rats exhibited a gradual reduction in the number of
      rotations induced by methamphetamine compared to vehicle-injected rats. These
      rats also showed a significant improvement in rota-rod performance. At 15 weeks
      after transplantation, immunoreactivities for tyrosine hydroxylase (TH) and
      dopamine transporter (DAT) in the striatum were significantly recovered in rats
      grafted with ES or ES-N cells compared to vehicle-injected rats. These results
      suggest that intrastriatal-transplantation of ES or ES-N cells improved the
      dopaminergic function and subsequently recover behavioral dysfunction in focal
      ischemic rats.

PMID- 16959415
TI  - The Ran binding protein RanBPM interacts with TrkA receptor.
AB  - RanBPM as a novel binding protein can interact with neurotrophin receptor p75NTR
      and tyrosine kinase receptor Met which has a similar tyrosine kinase structure as
      receptor TrkA has. Whether RanBPM interacts with neurotrophin receptor TrkA has
      not been established to date. In this study, using yeast two-hybrid system, it
      was identified that RanBPM bound to the intracellular domain (ICD) of
      neurotrophin receptor TrkA through its SPRY motif. We confirmed the formation of
      complexes between RanBPM and TrkA by co-immunoprecipitation studies and GST pull
      down assays. The region of TrkA interacted with the SPRY domain of RanBPM was
      located in its tyrosine kinase domain. Furthermore, coimmunoprecipitaiton
      revealed endogenous RanBPM and receptors TrkA did interact in several mammalian
      cell lines. It was found that the overexpression of RanBPM could inhibit NGF
      induced increase of nuclear factor of activated T cells (NFAT) dependent
      luciferase expression through its interaction with receptor TrkA, and NFAT
      transcriptional activity plays an important role in neuronal signal transduction.
      These data suggested that RanBPM could participate in neurotrophin-mediated gene
      transcription and expression by its binding to TrkA.

PMID- 16959416
TI  - Targeted deletions of Mel1a and Mel1b melatonin receptors affect pCREB levels in
      lactotroph and pars intermedia cells of mice.
AB  - The actions of the pineal hormone melatonin depend on two types of membrane
      bound, G-protein-coupled receptors: the MT1 (Mel1a) and MT2 (Mel1b) melatonin
      receptors. An important target of melatonin is the hypophysial pars tuberalis
      that controls the activity of lactotroph cells in the pars distalis (PD). To
      identify the melatonin receptor type responsible for regulation of the lactotroph
      cells in pars distalis we studied the levels of Ser133-phosphorylated pCREB in
      immunocytochemically identified lactotroph cells of wild-type mice (MelAABB) and
      of mice bearing targeted deletions of the Mel1a receptor (MelaaBB), the Mel1b
      receptor (MelAAbb) or of both receptor types (Melaabb) at five different time
      points of a light/dark cycle. Moreover, we analyzed whether pCREB levels in pars
      intermedia cells also depend on intact melatonin signal transduction cascades. In
      wild type and MelAAbb mice the percentage of lactotroph cells with nuclear pCREB
      immunoreactions varied significantly over a 24 h period, whereas in MelaaBB and
      Melaabb mice no significant differences were found between the five time points
      analyzed. pCREB levels in the pars intermedia did not show rhythmic variation in
      wild type or Melaabb animals but wild type mice had higher pCREB levels than
      Melaabb. Our results indicate that Mel1a and Mel1b melatonin receptors are
      involved in the control of the activity state of lactotroph and pars intermedia
      cells of mice.

PMID- 16959417
TI  - Rhinal-hippocampal coupling during declarative memory formation: dependence on
      item characteristics.
AB  - Lesion and imaging studies have demonstrated that encoding and retrieval of
      declarative memories, i.e. consciously accessible events and facts, depend on
      operations within the rhinal cortex and the hippocampus, two substructures of the
      medial temporal lobe. Analysis of intracranially recorded EEG in presurgical
      epilepsy patients revealed that successful memory formation is accompanied within
      one second by a transient enhancement and later decrease of Rhinal-hippocampal
      phase synchronization in the gamma range, as well as enhanced connectivity in the
      low-frequency range. In these studies, words with a high frequency of occurrence
      were used as stimulus material. Here, we re-examined these effects in another
      group of 10 presurgical epilepsy patients, this time not only for high-frequency,
      but also for low-frequency words. For successfully memorized compared to later
      forgotten high-frequency words we again observed an early phase coupling and
      later decoupling within the gamma range, as well as enhanced coupling within the
      sub-gamma range. However, for remembered as compared to forgotten low-frequency
      words clear synchronization increases were only observed for the delta band, but
      not for the gamma band. Our data suggest, that broadband Rhinal-hippocampal
      coupling including the gamma range only occurs, when significant semantic
      associations are processed within rhinal cortex, as is the case for high
      frequency words.

PMID- 16959418
TI  - Soluble factors from neuronal cultures induce a specific proliferation and
      resistance to apoptosis of cognate mouse skeletal muscle precursor cells.
AB  - The mechanisms or the physiological events, which control the regeneration of
      skeletal muscle through muscle precursor cell multiplication and differentiation,
      are still largely unknown. To address the question of the involvement of neurons
      in this process, skeletal muscle progenitors were grown in the presence of
      conditioned media obtained from 3-day-old cultures of embryonic neurons (derived
      from either the dorsal or the ventral region of 11-day-old mouse embryos) or
      media conditioned with satellite cells. Strikingly, only satellite cells cultured
      in medium conditioned from ventral embryonic neurons exhibited increased
      proliferation, as well as resistance to staurosporine (STS)-induced apoptosis.
      Our results suggest the existence of specific anti-apoptogenic neural soluble
      signals, which could be involved in skeletal muscle regeneration pathways.

PMID- 16959419
TI  - A family-based association study of kinesin heavy chain member 2 gene (KIF2) and
      schizophrenia.
AB  - Schizophrenia is a multifactorial disease characterized by multiple genetic
      susceptibility elements. The human KIF2 gene represents an orthologue of the
      murine Kif2a, which plays an important role in the transport of various
      membranous organelles and protein complexes on microtubules. To examine whether
      this gene is involved in schizophrenia etiology, we undertook studies of
      transmission disequilibrium in a cohort of affected family samples to test for
      association. Although, we failed to detect any positive results in single
      markers, a common two-SNP haplotype (rs2289883/rs464058, G/A) showed a
      significant association with the disease and a four-SNP haplotype (T/G/A/G) with
      a frequency of 23.4% was identified in parental chromosomes and showed a
      significant association with the disease (P=0.00795). Our results demonstrate
      that the KIF2 gene, located at 5q12.1, is a potential schizophrenia
      susceptibility gene.

PMID- 16959420
TI  - Evidence for spinal dorsal horn hyperexcitability in rats following sustained
      morphine exposure.
AB  - Repeated or sustained exposure to opioids can not only induce analgesia but also
      long lasting enhancements in pain sensitivity, a phenomenon reported clinically
      and in animals. In rats, opioid-induced abnormal pain can be readily measured
      following continued delivery of morphine and the recruitment of descending
      facilitatory influences appears essential for the genesis of this state. Here, we
      provide evidence that an increased excitability develops in neurons of the deep
      dorsal horn (DH), following 7-10 days of sustained delivery of morphine.
      Electrophysiological recordings were made in halothane-anesthetised animals
      implanted with osmotic minipumps containing either morphine (45 microg/0.5
      microl/h and 90 microg/0.5 microl/h) or saline. A separate group of naive animals
      was also used as controls. Sustained morphine exposure resulted in dose-related
      and modality-specific enhancements of DH neurons (C-fibre and Adelta-fibre evoked
      responses, non-potentiated responses) and expanded neuronal receptive fields, as
      mapped with low intensity mechanical punctate stimuli. Heat and mechanical
      stimulation of the hindpaw (brush and von Frey filaments) produced similar
      enhancements in morphine-treated rats compared to control rats, reflecting spinal
      hyperexcitability. Interestingly, wind-up itself was unaltered. These
      neuroadaptive changes could form the neuronal basis for the documented clinical
      and experimental reports of abnormal paradoxical pain after opioids. Since
      brainstem excitatory controls actively operate during prolonged opioid exposure,
      the sustained triggering of such influences may act alongside spinal mechanisms
      such as wind-up to enhance central sensitisation and alter CNS excitability.

PMID- 16959421
TI  - Increased serum glial cell line-derived neurotrophic factor immunocontent during
      manic and depressive episodes in individuals with bipolar disorder.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor from
      the transforming growth factor beta family, which plays a role in the development
      and function of hippocampal cells. Preclinical studies suggest that changes in
      neurotrophic growth factor systems might be involved in the pathophysiology of
      mood disorders including bipolar disorder (BD) [E.J. Nestler, M. Barrot, R.J.
      DiLeone, A.J. Eisch, S.J. Gold, L.M. Monteggia, Neurobiology of depression,
      Neuron 34 (2002) 13-25]. This is the first study to analyze GDNF immunocontent in
      BD subjects across different mood states, including mania, depression, and
      remission (euthymia). Fourty-four bipolar patients (14 depressed, 15 manic, and
      15 euthymic) and 14 healthy controls, diagnosed according to the Structural
      Clinical Interview for DSM-IV were studied. Serum GDNF immunocontent was measured
      using Western blotting. Serum GDNF immunocontent was increased in manic (F=42.31;
      p=0.001; one-way ANOVA) and depressed (F=42.31; p=0.004; one-way ANOVA) bipolar
      patients, but not in euthymic patients as compared with controls. Our results
      indicate that changes in GDNF immunocontent occur during acute major affective
      episodes in bipolar subjects. These results further support the role of
      neurotrophins in the pathophysiology of bipolar disorder. Whether the observed
      increase in GDNF immunocontent correspond to a pathological or an adaptive
      response remains to be determined.

PMID- 16959422
TI  - Effects of N-methyl-D-aspartate on extracellular citrulline level in the rat
      nucleus accumbens.
AB  - In vivo microdialysis combined with high-performance liquid chromatography and
      electrochemical detection was used to study effects of intraaccumbal infusion of
      N-methyl-D-aspartate (NMDA) on the content of extracellular citrulline (a nitric
      oxide co-product) in the medial nucleus accumbens of Sprague-Dawley rats. The
      intraaccumbal NMDA infusion (10-1000 microM) dose-dependently increased the local
      dialysate citrulline levels (193+/-7% and 258+/-7% versus basal for the 100 and
      1000 microM, respectively). The NMDA-induced increase of extracellular citrulline
      was completely prevented by intraaccumbal infusions through the dialysis probe
      both of 50 microM dizocilpine maleate (an NMDA antagonist) and of 0.5 mM N-nitro
      L-arginine (a nitric oxide synthase inhibitor). Local infusion of N-nitro-L
      arginine (0.5 mM) slightly decreased basal citrulline levels in the nucleus
      accumbens throughout the entire period of the infusion, whereas dizocilpine
      maleate (50 microM) had no long-lasting effect. These results suggest that NMDA
      receptor stimulation of the medial nucleus accumbens might cause a local nitric
      oxide synthase activation resulting in nitric oxide production in this brain
      area.

PMID- 16959423
TI  - The dysbindin gene (DTNBP1) and schizophrenia: no support for an association in
      the Korean population.
AB  - The dysbindin gene (DTNBP1) is located in chromosome 6p22.3, one of the regions
      of positive linkage for schizophrenia. A strong genetic association between
      DTNBP1 and schizophrenia has been replicated through many recent studies. In
      particular, dysbindin protein has been found to play a role in the glutamate
      neural transmission in the brain. In this study, we attempted to replicate the
      previously reported positive association between DTNBP1 and schizophrenia in the
      Korean population. Our sample included 194 patients with schizophrenia based on
      DSM-IV and 351 normal controls. We genotyped five SNPs including SNP A in
      promoter region of DTNBP1. The allele and genotype association were analyzed and
      the simulated haplotype was investigated as well. As the result, we could not
      find a significant association of DTNBP1 with schizophrenia in this Korean
      sample. Additional analysis of the subgroup of schizophrenia having familial
      loading of major psychiatric disorders did not show association, either. In
      summary, DTNBP1 is not likely to be a major susceptibility gene for schizophrenia
      in this Korean population. This result of no association also implies possible
      genetic heterogeneity of schizophrenia. Further studies with more dense SNPs of
      the whole gene sequence for various populations will be necessary to understand
      the genetic contribution of DTNBP1 for the development of schizophrenia.

PMID- 16959424
TI  - APP23 mice display working memory impairment in the plus-shaped water maze.
AB  - Alzheimer's disease (AD) patients typically present short-term memory deficits,
      before long-term memory capacity declines with disease progression. Several
      studies have described learning and memory deficits in the APP23 mouse model. Our
      group reported a decline of learning and memory capacities from the age of 3
      months onwards using a hidden-platform Morris water maze (MWM). The aim of the
      present study was to evaluate working and reference memory in APP23 mice in the
      same plus-shaped water maze. The transgenic mice had slower learning curves;
      however, consolidation of the learned information appeared intact in this
      learning paradigm. This report demonstrates impairment of working memory in this
      transgenic Alzheimer model.

PMID- 16959425
TI  - Association between polymorphisms in serotonin 2C receptor gene and attention
      deficit/hyperactivity disorder in Han Chinese subjects.
AB  - Attention deficit hyperactivity disorder (ADHD) is much more frequent in males
      than females, so several genes on the X chromosome (e.g., MAOA and MAOB) have
      been pursued as candidates for influencing risk for the disorder. HTR2C is also
      located on the X chromosome. In the current study, we examined the relationship
      between the C-759T and G-697C polymorphisms of HTR2C and ADHD in 488 Han Chinese
      families. Transmission Disequilibrium Test (TDT) analysis showed that the -759C
      allele, the -697G allele, and haplotype -759C/-697G were significantly over
      transmitted to affected probands, while haplotypes -759C/-697C and -759T/-697C
      were under-transmitted. When families were divided into three subtypes according
      to the diagnosis of probands, the -697G allele and haplotype -759C/-697G were
      significantly over transmitted to ADHD-C probands, while haplotype -759T/-697C
      was under-transmitted to these individuals; however, no biased transmission of
      any allele or haplotype was observed for probands with ADHD-I, suggesting that
      different subtypes of ADHD have different genetic influences. Our findings
      highlight the need to explore the role of 5-HT2C receptor dysfunction in the
      pathogenesis of ADHD.

PMID- 16959426
TI  - Reversible inactivation of the dorsal raphe nucleus blocked the antipanic-like
      effect of chronic imipramine in the elevated T-maze.
AB  - Antidepressant drugs are effective in the treatment of panic in human panic
      disorder patients. One hypothesis is that the anti-panic effects of
      antidepressant drugs are mediated by an increase in the activity of serotonergic
      neurons within dorsal raphe nucleus (DRN) leading to an increase in serotonin
      mediated inhibition of the dorsal periaqueductal gray (DPAG). In order to test
      this hypothesis, we investigated the effects of reversible inhibition of the DRN
      on behavior in the elevated T-maze (ETM) in control rats and rats chronically
      treated with imipramine. Rats were injected daily with imipramine (15 mg/kg i.p.)
      or saline for 24 days. A guide cannula was implanted in the DRN on day 14.
      Lidocaine (4%, 0.2 microL) or saline was injected into the DRN 10 min before the
      test in the ETM followed immediately by the open-field test (day 21). Three days
      later, the infusions were crossed-over, rats microinjected into the DRN with
      saline in the first trial received lidocaine and vice versa, and the behavioral
      tests were repeated (day 24). Chronic saline plus lidocaine in the DRN and
      chronic imipramine (plus saline or lidocaine in the DRN) impaired inhibitory
      avoidance, indicating an anxiolytic effect. In the one-way escape, lidocaine
      facilitated it, suggesting a panicogenic effect, while chronic imipramine
      impaired it, which is indicative of a panicolytic effect. Moreover, lidocaine
      blocked the facilitatory effect of chronic imipramine. The locomotor activity in
      the open field was not changed by any treatment compared to the control group.
      These effects were congruent with the hypothesis that the DRN has a dual effect
      on anxiety: increasing learned anxiety and decreasing innate anxiety. Moreover,
      they suggest that the DRN exerts a crucial role in the antipanic-like effect of
      chronic imipramine in the ETM.

PMID- 16959428
TI  - Transmission microscopy without lenses for objects of unlimited size.
AB  - We demonstrate experimentally, for the first time, a new form of lensless
      microscopy. The image we obtain contains the entire wavefunction emanating from
      the sample. Large scale, quantitative phase information can be measured, unlike
      in conventional (Zernike) methods. For light optical experiments, we can dispense
      with expensive high-quality lenses and the very large working distances available
      would allow remote monitoring of e.g., environmental cells without compromising
      resolution. In short wavelength microscopy (X-rays and electrons), where lens
      components are of very limited numerical aperture, the technique has
      revolutionary implications: objects of any lateral size or shape can be used and,
      for transmission electron imaging, resolution down to the scale of the wavelength
      is likely to be limited only by the presence of atomic vibrations.

PMID- 16959427
TI  - Adjunctive self-hypnotic relaxation for outpatient medical procedures: a
      prospective randomized trial with women undergoing large core breast biopsy.
AB  - Medical procedures in outpatient settings have limited options of managing pain
      and anxiety pharmacologically. We therefore assessed whether this can be achieved
      by adjunct self-hypnotic relaxation in a common and particularly anxiety
      provoking procedure. Two hundred and thirty-six women referred for large core
      needle breast biopsy to an urban tertiary university-affiliated medical center
      were prospectively randomized to receive standard care (n=76), structured
      empathic attention (n=82), or self-hypnotic relaxation (n=78) during their
      procedures. Patients' self-ratings at 1 min-intervals of pain and anxiety on 0-10
      verbal analog scales with 0=no pain/anxiety at all, 10=worst pain/anxiety
      possible, were compared in an ordinal logistic regression model. Women's anxiety
      increased significantly in the standard group (logit slope=0.18, p<0.001), did
      not change in the empathy group (slope=-0.04, p=0.45), and decreased
      significantly in the hypnosis group (slope=-0.27, p<0.001). Pain increased
      significantly in all three groups (logit slopes: standard care=0.53,
      empathy=0.37, hypnosis=0.34; all p<0.001) though less steeply with hypnosis and
      empathy than standard care (p=0.024 and p=0.018, respectively). Room time and
      cost were not significantly different in an univariate ANOVA despite hypnosis and
      empathy requiring an additional professional: 46 min/161 dollars for standard
      care, 43 min/163 dollars for empathy, and 39 min/152 dollars for hypnosis. We
      conclude that, while both structured empathy and hypnosis decrease procedural
      pain and anxiety, hypnosis provides more powerful anxiety relief without undue
      cost and thus appears attractive for outpatient pain management.

PMID- 16959429
TI  - Detection of specific hydatid antigens and antibodies in serum and urine of
      experimentally infected sheep.
AB  - Immunodiagnostic confirmation of cystic human hydatidosis is frequently required
      before surgical intervention or of chemotherapy. However, it remains inadequate
      to detect specific antibodies or antigens in some confirmed cases of
      echinococcosis. This study was carried out to investigate the accuracy of three
      different immunodiagnostic tests for detection of specific circulating antigens
      or antibodies in the serum and urine of 13 experimentally infected sheep. For
      this purpose, Echinococcus granulosus were collected from small intestine of
      experimentally infected dogs, and 2000 taenid eggs were orally administered to
      each of the 13 sheep. There were six other sheep, which were kept as the control
      group. Biweekly serum and urine samples were collected from all the sheep for 4
      months after infection. The sera were subjected to indirect hemagglutination test
      and the concentrated urine samples were subjected to coagglutination and counter
      immunoelectrophoresis tests. The results revealed that the sensitivity of these
      tests in detecting the hydatid antigens in the urine or antihydatid antibodies in
      the serum of the infected sheep reached their maximum in 12th and 13th week after
      infection; then it decreased in the following weeks. Examination of the non
      infected sheep samples throughout the experiment showed that the aforesaid
      findings were specific only to the infected sheep. It seems that the appearance
      of specific hydatid antigen in urine and its antibodies in the serum were
      simultaneous. Although these tests are highly specific, false negative outcomes
      were encountered in their detection of cystic echinococcosis. In general, it
      seems rational to establish some series of diagnostic procedures in order to
      reveal antibodies and antigen of metacestode in serum and urine of the patients.

PMID- 16959430
TI  - Field testing of a fenbendazole treatment combined with hygienic and management
      measures against a natural Giardia infection in calves.
AB  - The need of a combination of animal treatment and environmental measures against
      a natural Giardia infection in calves between the age of 1 and 6 months was
      emphasized and evaluated. Ten commercial farms with a total of 94 calves
      suffering from chronic diarrhea, ill thriving and impaired growth, were included
      in two subsequent studies. The first study indicated that treatment of all
      animals with fenbendazole at 15 mg/kg during 3 consecutive days combined with
      environmental measures on the final day of treatment, which were either removal
      of bedding, thorough cleaning and ammonia 10% disinfection or relocation of the
      treated animals to a Giardia free environment, resulted in a total reduction in
      cyst excretion for at least 2 weeks. In the second study, the immunofluorescence
      assay (Merifluor Cryptosporidium/Giardia; Meridian Diagnostics Inc., Cincinnati,
      Ohio) was used quantitatively and confirmed that the combination of treatment and
      environmental measures resulted in a total reduction of cyst excretion during 2
      weeks and in a significant (P<0.05; >or=98.0%) reduction of the cyst excretion
      until at least 4 weeks after treatment. Furthermore, there was a noticeable
      improvement of the clinical symptoms in all animals towards day 28 after
      treatment and 4 months after treatment health in all calves was normal.

PMID- 16959431
TI  - Trichinella: differing effects of antigens from encapsulated and non-encapsulated
      species on in vitro nitric oxide production.
AB  - Trichinellosis is a cosmopolitan zoonotic disease affecting a wide variety of
      animals, including man. Non-encapsulated and encapsulated species diverge with
      respect to their developmental strategies. Little is known at the molecular level
      about parasite-derived mediators responsible for host muscle cell transformation
      occurring during trichinellosis. In this context, host-parasite relationships in
      Trichinella-infected animals could be related to different host-immune and cell
      mediators, e.g. nitric oxide (NO). Here, we investigate the
      stimulatory/inhibitory role of L1 antigens from four encapsulated (T. spiralis,
      T. britovi, T. nelsoni and T. nativa) and one non-encapsulated (T.
      pseudospiralis) Trichinella species on NO production from rat macrophages in
      vitro. Our results demonstrate that encapsulated and non-encapsulated Trichinella
      species differ in their capacity to stimulate the secretion of NO from host
      macrophages. Biological significance of these differences should be further
      assessed in the available experimental models.

PMID- 16959432
TI  - Irinotecan in the treatment of colorectal cancer.
AB  - Irinotecan, a water-soluble, semisynthetic derivative of camptothecin, is a key
      component of first- and second-line treatment regimens for metastatic colorectal
      cancer (CRC). In the first-line treatment of metastatic CRC, the results of two
      prospective, multicenter phase III trials have shown that the combination of
      irinotecan with bolus or infusional 5-fluorouracil (5FU)/leucovorin (LV) can
      significantly prolong survival compared with 5FU/LV alone, with a manageable side
      effects profile. In addition, irinotecan-based regimens, with or without
      oxaliplatin, may improve resectability of metastases and further increase patient
      survival. Studies of irinotecan in the first-line setting in combination with
      newer agents, such as bevacizumab, have shown impressive overall survival. In the
      second-line setting, irinotecan has demonstrated efficacy superior to that of
      best supportive care. Initial studies of irinotecan plus bolus 5FU/LV, and the
      preliminary results from trials of irinotecan plus infusional 5FU/LV in the
      adjuvant setting, have been disappointing; however, for the largest trial, the
      Pan-European Trial in Adjuvant Colon Cancer, results with sufficient follow-up
      are pending. Irinotecan has an acceptable tolerability profile and is not
      associated with cumulative toxicities in patients with metastatic CRC; regimens
      containing irinotecan extend treatment duration and improve survival. New
      regimens and adjunctive therapies are being explored to reduce the incidence of
      common complications of irinotecan treatment, such as diarrhea and neutropenia.

PMID- 16959433
TI  - Prenatal influences on brain dopamine and their relevance to the rising incidence
      of autism.
AB  - The incidence of autism has risen 10-fold since the early 1980s, with most of
      this rise not explainable by changing diagnostic criteria. The rise in autism is
      paradoxical in that autism is considered to be one of the most genetically
      determined of the major neurodevelopmental disorders and should accordingly
      either be stable or even declining. Because a variety of epigenetic influences,
      particularly those occurring during the prenatal period, can override or
      masquerade as genetic influences, these should be considered as prime
      contributors to the recent increase of autism. Prenatal influences on dopamine
      activity are especially well-documented, including the effects of maternal
      psychosocial stress, maternal fever, maternal genetic and hormonal status, use of
      certain medications, urban birth, and fetal hypoxia. All of these factors have
      been implicated in the genesis of autism, which is characterized by a
      "hyperdopaminergic" state based on evidence from monkey and human behavioral
      studies, pharmacological studies in humans, and a left-hemispheric predominance
      of both dopamine and autistic-like symptoms. Chronically high maternal levels of
      dopamine caused by the pressures of increasingly urbanized societies and by
      changing maternal demographics such as increased workforce participation,
      educational achievement level, and age at first birth, may be especially
      significant epigenetic contributors to the recent autism rise.

PMID- 16959434
TI  - Bronchioloalveolar carcinoma of mixed mucinous and nonmucinous type:
      immunohistochemical studies and mutation analysis of the p53 gene.
AB  - Bronchioloalveolar carcinoma of mixed mucinous and nonmucinous type fulfilling
      the 1999 WHO criteria is rare. Here, we report a case of this type of tumor
      determined entirely by histological examinations. A 57-year-old man was
      incidentally found to have a demarcated 3cm mass in his lower lobe of the right
      lung. The tumor was composed of tall columnar cells containing cytoplasmic
      mucins, cuboidal cells without mucins, and intermediate cell types with lepidic
      growth patterns. Tumor cells were distributed within a region of 2cm in diameter,
      and no stromal, vascular, or pleural invasion was observed.
      Immunohistochemically, both the mucinous and nonmucinous components were positive
      for cytokeratin 7, TTF-1, and E-cadherin, and negative for cytokeratin 20,
      consistent with the results for nonmucinous bronchioloalveolar carcinoma. No
      mutations were detected in exons 5-8 of the p53 gene. The present tumor was
      composed mainly of morphologically mucinous bronchioloalveolar carcinoma, but
      presented different immunohistochemical profiles of ordinary mucinous
      bronchioloalveolar carcinoma. This case suggests that the mucinous component in
      bronchioloalveolar carcinoma of mixed mucinous and nonmucinous type has
      characters dissimilar to conventional mucinous bronchioloalveolar carcinoma, and
      is probably derived from the nonmucinous component.

PMID- 16959435
TI  - Pathological findings of uterine leiomyomas and adenomyosis following uterine
      artery embolization.
AB  - Uterine artery embolization (UAE) is an effective and accepted treatment option
      for symptomatic uterine leiomyoma. Between 2000 and 2005, 91 women were treated
      using this method, and were prospectively followed at our institution. Twenty of
      them subsequently underwent surgery. One of these patients was subjected to four
      surgical procedures. We describe the pathological findings of 23 surgical
      specimens obtained from these 20 patients. The embolic material used consisted of
      tris-acryl gelatin microspheres (TGMS) in 15 patients (18 surgical specimens),
      polyvinyl alcohol particles (PVA) in three patients, and a combination of PVA and
      TGMS in two patients. Histologically, of the 23 specimens examined, 20 were
      diagnosed as leiomyomas, and three as adenomyosis. Particles used for
      embolization were found in all but three specimens. Necrosis was present in 15 of
      20 leiomyoma specimens. Hyaline necrosis was found in 12 specimens, coagulative
      necrosis in one case, and a combination of hyaline and coagulative or suppurative
      necrosis in two cases. The foci of adenomyosis remained unaltered.

PMID- 16959436
TI  - Testing the dual pathway hypothesis to substance use in adolescence and young
      adulthood.
AB  - BACKGROUND: We tested the dual pathway hypothesis to substance use which posits
      that substance use can develop via internalizing symptoms or deviant behaviors.
      METHOD: Using data from the Add Health study, we used latent class analysis to
      define subgroups based on patterns of substance use, and logistic regression
      procedures to evaluate the prospective association between symptoms of
      depression, deviance, and the individual substance use patterns. RESULTS: Groups
      representing similar patterns of substance use were identified in both
      adolescence and young adulthood. Some support for the dual pathway hypothesis was
      demonstrated. Deviance was prospectively associated with substance group
      assignment in both adolescence and young adulthood, while depression uniquely
      predicted assignment to the smoking group in young adulthood among females.
      CONCLUSIONS: Further testing of the dual pathway hypothesis should be built on
      diverse pattern-centered approaches able to explore the presence of population
      subgroups.

PMID- 16959437
TI  - Prevalence of opioid analgesic injection among rural nonmedical opioid analgesic
      users.
AB  - OBJECTIVE: The purpose of this study was to examine the prevalence and correlates
      of opioid analgesic injection (OAI) in a cohort of rural opioid analgesic users.
      METHODS: Cross-sectional study of 184 participants from rural Appalachian
      Kentucky. RESULTS: The majority of participants were male (54.9%), white (98.4%)
      and the median age was 30 years (interquartile range: 24-37). The self-reported
      lifetime prevalence of injection drug use (IDU) was 44.3%, with 35.3% of
      respondents reporting injection of oral opioid analgesic formulations. The
      prevalence of self-reported hepatitis C (HCV) was 14.8%, significantly greater
      than those not injecting opioid analgesics (1.7%) (p<0.001). Receptive needle
      sharing, distributive needle sharing and sharing of other injection paraphernalia
      was reported by 10.5%, 26.3%, and 42.1% of those currently injecting,
      respectively. CONCLUSIONS: Opioid analgesic injection was more prevalent in this
      rural population than has been found in previous reports. This study suggests a
      rising problem with injecting among rural opioid users, a problem more typically
      associated with urban drug users. Educating injectors of opioid analgesics on
      safe needle practices is necessary in order to curb the transmission of HIV, HCV,
      and other infectious diseases. Further study on the longitudinal course of opioid
      analgesic injection in this population appears warranted.

PMID- 16959438
TI  - Predictors of non-fatal overdose among a cohort of polysubstance-using injection
      drug users.
AB  - BACKGROUND: Non-fatal overdose is a major determinant of morbidity among
      injection drug users (IDU). We sought to evaluate factors associated with non
      fatal overdose among IDU in Vancouver. METHODS: We examined non-fatal overdose
      among participants in the Vancouver Injection Drug Users Study. Correlates of non
      fatal overdose occurring between 1996 and 2004 were identified using generalized
      estimating equations (GEE). RESULTS: There were 1587 participants included in
      this analysis, including 576 (36%) women. At baseline, 750 (47%) reported a
      history of non-fatal overdose. In total, 985 reports of non-fatal overdose were
      made during follow-up by 519 (32.7%) participants. In multivariate GEE analyses,
      factors independently associated with non-fatal overdose included: heroin
      injection (AOR=2.67), cocaine injection (AOR=2.01), benzodiazepine use
      (AOR=2.00), requiring help injecting (AOR=1.58), binge drug use (AOR=1.52),
      homelessness (AOR=1.38), alcohol use (AOR=1.32), street injecting (AOR=1.22), non
      injectable opiate use (AOR=1.16), speedball use (AOR=1.15), and recent
      incarceration (AOR=1.14). Younger age (AOR=0.99) and methadone use (AOR=0.51)
      were protective. CONCLUSIONS: We found that non-fatal overdose was common among
      local IDU. Non-fatal overdose was associated with several factors that may be
      amenable to intervention, including opiate and stimulant use, and the
      characteristic of requiring help with injecting. These findings indicate the need
      for the ongoing development of structural interventions to address this common
      cause of morbidity among IDU.

PMID- 16959439
TI  - Escherichia coli BL21(DE3) chromosome contains a group II capsular gene cluster.
AB  - During our study of de novo synthesis of Escherichia coli K1 capsular
      polysaccharides, we found that E. coli BL21(DE3) has a capsular gene cluster,
      similar to those of group II capsular E. coli strains. Analysis of the nucleotide
      sequence of the E. coli BL21(DE3) gene cluster showed homologues to all group II
      regions 1 and 3 genes and the presence of an IS1 element in one of the region 2
      ORFs, which likely prevents capsule expression. Complementation analysis showed
      that region 1 and 3 genes encode functional proteins that are sufficient for the
      export of newly synthesized polysaccharide. The gene products of Bl21(DE3) kpsC
      and kpsS supported in vitro de novo synthesis of K1 polysaccharide when co
      expressed with K1 NeuE and NeuS. Sequence homology between BL21(DE3) region 2
      open reading frames and capsule-related genes in other bacteria such as
      Haemophilus influenzae serotype b, suggests that the encapsulated ancestor of
      BL21(DE3) may have produced a ribose/ribitol-phosphate containing polysaccharide.

PMID- 16959440
TI  - A new test of phylogenetic model fitness addresses the issue of the basal
      angiosperm phylogeny.
AB  - We readdress the issue of phylogeny of the basal extant angiosperms employing a
      source previously not systematically investigated, specifically, the non-coding
      sequences of cpDNA. Comparison of trees with and without grasses or the outgroup
      (Pinus) in our analyses revealed no rearrangements in tree topology that might be
      expected if LBA were distorting the position of the magnoliids. For each model
      applied, irrespective of whether monocots or ANITA members appeared basally
      divergent, the orchid Phalaenopsis assumed the same position on the trees with
      the reduced taxon set as did the branch bearing the orchid plus the grasses in
      the full alignment. However, our new test of model fitness revealed a different
      flaw influencing the placement of monocots, which is related to model mis
      specification. This flaw similarly affects the full alignment and the alignment
      with grasses removed. In both cases the models favouring a relatively derived
      position for the monocots and basal placement of the branch of Amborella plus
      Nymphaea provide better overall prediction of the observed data structure. In the
      view of apparent unsuitability of the bootstrap method for large data sets, our
      novel test provides a new means of exploring conflicts caused by systematic
      errors in phylogenetic analyses.

PMID- 16959441
TI  - Torque teno virus (TTV) is highly prevalent in the European wild boar (Sus
      scrofa).
AB  - The present study represents the first survey of Torque teno virus (TTV)
      prevalence in European wild boar (Sus scrofa). The prevalence of two distinct TTV
      genogroups in 178 Spanish wild boar sera from different geographic regions,
      management conditions, gender and age was determined by a nested PCR method. The
      overall prevalence of TTV genogroups was 84% (58% for genogroup 1 and 66% for
      genogroup 2), and differences between genogroup prevalence were observed
      depending on the geographical region analysed. Significantly higher prevalence
      for TTV genogroup 2 was found in fenced managed wild boar, juvenile animals and
      females. No other significant differences in TTV genogroup prevalence were
      observed. The phylogenetic analysis of nucleotide sequences obtained from the
      untranslated region of selected samples revealed that the same TTV genogroups are
      infecting wild boar and domestic pig. The results indicate that TTV is apparently
      ubiquitous in European wild boar populations.

PMID- 16959442
TI  - Prevalence of shiga toxin-encoding bacteria and shiga toxin-producing Escherichia
      coli isolates from dairy farms and county fairs.
AB  - Shiga toxin-encoding bacteria (STB) and shiga toxin-producing Escherichia coli
      (STEC) were detected and isolated from dairy cattle and their farm environment
      and from manure piles at Minnesota (MN) county fairs from 2001 to 2002. A total
      of 2,540 samples were collected from 28 dairy cattle farms (8 organic and 20
      conventional), 17 calf pens (5 organic and 12 conventional), and 12 county fairs.
      STB were detected from 71 (3.2%) of 2208 fecal samples with 20 (71.4%) of 28
      dairy farms having at least one positive animal sample. In samples collected from
      conventional farms, 41 (2.3%) of 1750 fecal samples were STB-positive and 13
      (65%) of 20 farms had at least one positive animal. Thirty (6.6%) of 458 fecal
      samples from organic farms were STB-positive and 7 (87.5%) of 8 farms had at
      least one positive animal. STB was detected from 31 (17.4%) of 178 samples and 7
      (58.3%) out of 12 manure piles at county fairs. A total of 43 STEC isolates were
      recovered and belonged to 26 different serotypes (19 O and 18 H types). Among
      STEC, 60.5% possessed only stx1, 30.2% stx2, and 9.3% both stx1 and stx2. The
      genes eae and hlyA were detected in more than 50% of the STEC isolates. STB can
      be found on most dairy cattle farms including organic and conventional herds and
      county fairs. The presence of these potentially pathogenic bacteria in county
      fairs may pose a risk to the public who have contact with cattle or their
      environment.

PMID- 16959444
TI  - Effects of experimental inoculation of bovine respiratory syncytial virus in
      different inbred mice lineages: establishment of a murine model for BRSV
      infection.
AB  - Bovine respiratory syncytial virus (BRSV), a member of the subfamily
      Pneumovirinae, family Paramyxoviridae, is a major cause of respiratory disorders
      in young cattle. A number of studies were conducted to validate a reliable animal
      model for the infection, since BRSV inoculation on the natural host is costly and
      often unsuccessful. Unfortunately, after inoculation of BRSV in Balb/C mice,
      viral replication may be detected; however, evident pathological alterations are
      absent on the experimentally infected animals. In order to establish a mice model
      that could be used further for preliminary studies of pathological and
      immunological aspects of BRSV infection, three mice inbred lineages (Balb/C, A/J
      and C57BL6), possessing different genetic backgrounds, were tested about its
      susceptibility to the inoculation with BRSV. Animals were inoculated through the
      nasal and ocular routes and were observed after inoculation. At 7 days post
      inoculation (dpi) animals were necropsied and virological (virus isolation and
      viral nucleic acid amplification) as well as histopathological examinations were
      performed. A/J and C57BL6 showed interstitial pneumonia, when compared to the
      Balb/C group. These findings shows that mice may constitute a suitable model for
      the study of BRSV infections, depending on the mice strain used for experimental
      inoculations.

PMID- 16959443
TI  - Biofilm formation by field isolates and reference strains of Haemophilus
      parasuis.
AB  - The ability to form biofilms for a total of 80 field isolates and 15 reference
      strains of Haemophilus parasuis, the etiological agent of Glasser's disease, was
      tested by glass tube and polystyrene microtiter plate assays. A total 43% of
      field isolates, including strains representing 13 serovars (except serovars 3 and
      8) and non-typable strains, exhibited the ability to form biofilms at different
      levels via polystyrene microtiter plate assays. Among the reference strains
      representing 15 serovars, only serovars 2, 9, 12, 13 and 15 could not form
      biofilms on the polystyrene surface. A total of 85% of the strains forming
      biofilms at air-liquid interfaces in glass tubes also formed biofilms on
      polystyrene surfaces. Generally, non-virulent serovars showed a higher degree of
      biofilm formation than virulent serovars. The biofilm formation phenotype of most
      strains was maintained when cultures were passaged on agar and in broth. H.
      parasuis from the nasal cavities of pigs experimentally infected with biofilm
      positive bacteria maintained the biofilm formation phenotype, whereas bacteria
      recovered from the lung and brain lost the ability to form biofilms. The biofilm
      negative strains did not recover the ability to form biofilms via experimental
      infection. Our data indicate that most serovars of H. parasuis could form
      biofilms in vitro, and the biofilm formation phenotype is associated with the
      recovery site of the strains and is maintained when bacteria are passaged in
      vitro and in the upper respiratory tract.

PMID- 16959445
TI  - Nutrigenomics: feeding the genes for improved fertility.
AB  - The post genomic era will result in many new molecular tools for evaluating the
      factors influencing fertility and reproductive performance in domestic livestock
      and poultry. There is currently considerable interest and practical merit in
      examining the regulatory steps involved in the process of gene transcription.
      Currently, oligo-based and cDNA microarray techniques make it possible to
      understand many of the factors controlling the regulation of gene transcription
      and globally evaluate gene expression profiles by looking at the relative
      abundance of gene-specific mRNA in tissues. These techniques provide an
      unprecedented amount of information and are only now being used to examine key
      reproductive, developmental, and performance characteristics in cattle. They also
      promise to provide a tremendous amount of new information that can be used to
      understand and diagnose key issues that limit reproductive performance. The
      science of nutrigenomics has begun to use information obtained from basic studies
      of the genome to evaluate the effects of diet and nutrient management schemes on
      gene expression. Preliminary studies have shown the value of such techniques and
      suggest that it will be possible to use specific gene expression patterns to
      evaluate the effects of nutrition on key metabolic processes relating to
      reproductive performance. While the effects of nutrition on fertility are only
      partially understood, modern nutrigenomics will undoubtedly play a key role in
      developing strategies for addressing some of the limitations in reproductive
      performance.

PMID- 16959446
TI  - Synthetic nano-low density lipoprotein as targeted drug delivery vehicle for
      glioblastoma multiforme.
AB  - The low density lipoprotein (LDL) receptor has been shown to be upregulated in
      GBM tumor cells and is therefore a potential molecular target for the delivery of
      therapeutic agents. A synthetic nano-LDL (nLDL) particle was developed and tested
      to determine its utility as a drug delivery vehicle targeted to GBM tumors. nLDL
      particles were constructed by combining a synthetic peptide containing a lipid
      binding motif and the LDL receptor (LDLR) binding domain of apolipoprotein B-100
      with a lipid emulsion consisting of phosphatidyl choline, triolein, and
      cholesteryl oleate. Composition analysis, fast protein liquid chromatography, and
      electron microscopy revealed that nLDL was highly reproducible and intermediate
      in size between high density lipoprotein and LDL particles (10.5+/-2.8 nm
      diameter). The binding and uptake of fluorescently labeled nLDL particles was
      assessed using fluorescence microscopy. Uptake of nLDL was time dependent,
      exhibiting saturation at approximately 3 h, and concentration dependent,
      exhibiting saturation at concentrations greater than 5 microM peptide. Using
      Lysotracker as a cellular marker, nLDL co-localized with lysosomes. nLDL binding
      was eliminated by blocking LDLRs with suramin and nLDL inhibited binding of
      plasma LDL to LDLRs. Collectively these data strongly suggest that the synthetic
      nano-LDLs described here are taken up by LDLR and can serve as a drug delivery
      vehicle for targeting GBM tumors via the LDLR.

PMID- 16959447
TI  - The study of drug permeation through natural membranes.
AB  - In this study, natural membranes such as the outer membrane of Prunus persica
      (peach) and Lycopersicon esculentum (tomato), the inner layer of the egg of
      Gallus domesticus (hen) and the middle membrane of the Allium cepa (onion) were
      used as controlling barriers for permeation of some model drugs with different MW
      and lipophilicities. Drug permeation studies were done by using modified Franz
      diffusion cell. The permeation of drugs through these natural membranes was
      compared to permeation of them through human skin and synthetic cellophane
      membrane. Results showed that the rate and amount of diclofenac permeated through
      onion membrane was not significantly different from that with tomato (p>0.17),
      egg (p>0.29) and human skin (p>0.93). Permeation of diclofenac through tomato
      skin and cellophane was not significantly different (p>0.35). Permeation of
      diclofenac through all studied membranes except for human skin that follows the
      Fickian kinetic followed non-Fickian mechanism and their permeabilities were not
      significantly different from each other (p>0.05). Permeation of metronidazole
      through onion membrane and tomato skin were not significantly different from
      human skin (p>0.053 and 0.38, respectively). All membranes were significantly
      different from each other (p<0.0001) for permeation of erythromycin as a
      relatively large molecular weight and lipohilic molecule through human skin and
      other studied membranes. Permeation of diclofenac through human skin and
      metronidazole through egg and tomato skin followed Fick's first law. Diffusion of
      diclofenac through onion, tomato, egg, cellophane, and peach; metronidazole
      through onion, peach, cellophane, and human skin, and erythromycin through all
      studied membranes followed non-Fickian mechanism for diffusion. Statistical
      analysis showed the most similarity between onion and human skin for diclofenac,
      tomato and human skin for metronidazole, onion and cellophane for erythromycin.

PMID- 16959448
TI  - Recrystallization of fluconazole using the supercritical antisolvent (SAS)
      process.
AB  - The supercritical antisolvent (SAS) process was used to modify solid state
      characteristics of fluconazole. Fluconazole was recrystallized at various
      temperatures (60-80 degrees C) and pressures (8-16MPa) using dichloromethane
      (DCM) as a solvent. Acetone and ethanol were also employed as solvents. The
      fluconazole polymorphs prepared by the SAS process were characterized by
      differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), powder
      X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR) and
      scanning electron microscopy (SEM). Furthermore, the equilibrium solubility of
      the samples in aqueous solution was determined. Fluconazole anhydrate form I was
      obtained at low temperature (40 degrees C) and anhydrate form II was obtained at
      high temperature (80 degrees C). The variation of pressure during the SAS process
      may influence the preferred orientation. Anhydrate forms I and II were also
      obtained using various solvents. Therefore, it was shown that solid state
      characteristics of fluconazole, including the polymorphic form and preferred
      orientation, can be controlled by changing operating conditions of the SAS
      process such as temperature, pressure, and solvent.

PMID- 16959449
TI  - Performance comparison of neural network training algorithms in modeling of
      bimodal drug delivery.
AB  - The major aim of this study was to model the effect of two causal factors, i.e.
      coating weight gain and amount of pectin-chitosan in the coating solution on the
      in vitro release profile of theophylline for bimodal drug delivery. Artificial
      neural network (ANN) as a multilayer perceptron feedforward network was
      incorporated for developing a predictive model of the formulations. Five
      different training algorithms belonging to three classes: gradient descent, quasi
      Newton (Levenberg-Marquardt, LM) and genetic algorithm (GA) were used to train
      ANN containing a single hidden layer of four nodes. The next objective of the
      current study was to compare the performance of aforementioned algorithms with
      regard to predicting ability. The ANNs were trained with those algorithms using
      the available experimental data as the training set. The divergence of the RMSE
      between the output and target values of test set was monitored and used as a
      criterion to stop training. Two versions of gradient descent backpropagation
      algorithms, i.e. incremental backpropagation (IBP) and batch backpropagation
      (BBP) outperformed the others. No significant differences were found between the
      predictive abilities of IBP and BBP, although, the convergence speed of BBP is
      three- to four-fold higher than IBP. Although, both gradient descent
      backpropagation and LM methodologies gave comparable results for the data
      modeling, training of ANNs with genetic algorithm was erratic. The precision of
      predictive ability was measured for each training algorithm and their
      performances were in the order of: IBP, BBP>LM>QP (quick propagation)>GA.
      According to BBP-ANN implementation, an increase in coating levels and a decrease
      in the amount of pectin-chitosan generally retarded the drug release. Moreover,
      the latter causal factor namely the amount of pectin-chitosan played slightly
      more dominant role in determination of the dissolution profiles.

PMID- 16959450
TI  - Use of lidocaine-prilocaine patch for the mantoux test: Influence on pain and
      reading.
AB  - A formulation of a eutectic mixture of lidocaine-prilocaine (EMLA) changes basal
      skin perfusion. Its use for alleviating pain associated with the Mantoux test may
      modify the recruitment of sensitised lymphocytes and then the response to
      tuberculin test. Twenty-four healthy BCG-vaccinated volunteers (26.7+/-4.1 years)
      received on each forearm an intradermal injection of 10IU tuberculin, one of the
      forearms being randomly pre-treated for 1h with EMLA-patch 5%. Pain associated
      with the Mantoux test was evaluated using a visual analogue scale. The
      transversal diameter of the induration was read at 72h. Subjects with 6mm
      difference between diameters (i.e. twice the usual variation for a Mantoux test)
      were recorded. Results were compared using a paired t-test. When using lidocaine
      prilocaine prior to the test, a three-fold decrease in pain was noted (p<0.0001).
      Reading of the test were not affected by the lidocaine-prilocaine application
      (p=0.26). Four subjects had 6mm or more difference between their two tests, two
      of them having an induration greater than 15mm with lidocaine-prilocaine.
      Lidocaine-prilocaine reduces significantly pain associated with the Mantoux test
      but does not normally affect the test reading. However, when the induration is
      more than 15mm, a control without lidocaine-prilocaine has to be considered.

PMID- 16959451
TI  - Phase-sensitive polymer-based controlled delivery systems of leuprolide acetate:
      in vitro release, biocompatibility, and in vivo absorption in rabbits.
AB  - Leuprolide acetate (LA) is a synthetic analog of gonadotropin releasing hormone.
      It is effective in prostate cancer treatment only when its desired concentration
      in blood is maintained for longer duration. Therefore, the purpose of this study
      was to investigate the in vitro release, biocompatibility, and in vivo absorption
      of LA from phase-sensitive polymer delivery systems capable of delivering it at a
      controlled rate for longer duration. Phase-sensitive formulations were prepared
      by dissolving dl-polylactic acid (dl-PLA) in a mixture of organic solvents,
      benzyl benzoate (BB) and benzyl alcohol (BA). LA was incorporated into the
      polymer solution by homogenization. In vitro release was studied into 15 ml of
      releasing media contained in a vial which was maintained at 37 degrees C in a
      reciprocal shaking water bath. The amount of LA in the released samples was
      analyzed by stability indicating HPLC method. The biocompatibility of polymer
      formulations was investigated by in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. In vivo absorption of LA from delivery
      systems was studied in rabbits. Blood samples were analyzed for LA and
      testosterone contents by commercially available immunoassay kits. In vitro
      release studies showed a greater release of LA from formulations containing a
      greater proportion of BA (hydrophilic fraction) in the solvent mixture. In vitro
      biocompatibility study showed significantly (p<0.05) higher cell viability in
      growth media diluted with polymer extract than the control. In vivo absorption of
      LA and its effect on testosterone level in rabbits from the delivery system
      showed a sustained plasma level of LA up to 12 weeks which suppressed the
      testosterone plasma concentration to castration level beginning from 14th day
      until 90 days. Thus, phase-sensitive polymer delivery systems of LA were
      biocompatible and delivered LA at a controlled rate both in vitro and in vivo to
      keep testosterone plasma concentration at a castration level up to 3 months.

PMID- 16959452
TI  - In vitro evaluation of quercetin cutaneous absorption from topical formulations
      and its functional stability by antioxidant activity.
AB  - Recently, it was demonstrated that two different formulations containing
      quercetin inhibit the UVB-induced cutaneous oxidative stress and inflammation.
      Therefore, in the present study it was evaluated the functional stability of
      those formulations by the antioxidant activity, the release of quercetin from the
      formulations, and its skin retention using modified Franz diffusion cells. Both
      formulations tested ((1) non-ionic emulsion with high lipid content and (2)
      anionic emulsion with low lipid content) remained functionally (hydrogen-donating
      ability) stable during 180 days. Furthermore, quercetin was released from both
      formulations as determined using nitrocellulose membrane. In vitro antioxidant
      activity of retained quercetin into the skin was observed for both formulations
      as detected by the inhibition of malondialdehyde formation. The effect of
      quercetin retention was time-dependent for formulation 1. Concluding, this study
      demonstrates that quercetin remains functionally stable in formulations, and
      measuring the antioxidant activity is an efficient approach to evaluate quercetin
      skin retention with minimal interference of the tissue products. Furthermore, the
      present results on skin retention explain the previous study on quercetin in vivo
      activities, and together, these data suggest that formulations containing
      quercetin may be used as topical active products to control UVB-mediated
      oxidative damage of the skin.

PMID- 16959453
TI  - Rapid-onset intranasal delivery of metoclopramide hydrochloride Part II: Safety
      of various absorption enhancers and pharmacokinetic evaluation.
AB  - In the present study, several nasal absorption enhancers, used in metoclopramide
      hydrochloride (MCP HCl) nasal solutions, have been screened for their possible
      damaging effect in the in vitro human erythrocytes lysis experiment. Moreover,
      the in vivo leaching of biological markers from the rat nasal epithelium was used
      as a quantitative assessment for possible nasal mucosal irritation whereby the
      extent of release of total protein and lactate dehydrogenase (LDH) in the nasal
      lavage fluid was determined. Results showed that insignificant hemolysis from
      normal saline (P<0.05) occurred with the enhancer protamine sulphate while poly-l
      arginine and sodium cholate demonstrated very low (<15%) hemolysis and caused
      insignificant protein and LDH release from the rat nasal mucosa. Conversely,
      sodium deoxycholate and chitosan polymers (either of low or high molecular
      weight) showed high (>60%) hemolysis in vitro and the release of the biological
      markers in vivo was significantly higher (P<0.05) than the control solution (no
      enhancer). A significant correlation (P<0.05) existed between the enhancement
      effect of MCP HCl nasal absorption and the amounts of protein (r=0.85) and LDH
      (r=0.88). Furthermore, the pharmacokinetics of MCP HCl was determined after
      intravenous (IV), per-oral and intranasal administration of 10mg drug dose in
      rabbits. The application of a nasal spray (NS) solution containing 0.5% sodium
      cholate resulted in a significant improvement (P<0.05) in both the rate and
      extent of absorption of MCP HCl where the T(max) achieved was 23.3min as compared
      to 50min in case of the oral solution while the area under the serum
      concentration-time curve (AUC(0-infinity)) were 506.1, 434.9 and
      278.7microg/mlmin for IV, NS and oral solutions, respectively. These values
      corresponded to absolute bioavailabilities of 87.21 and 55.61% for the NS and
      oral solutions, respectively. It could thus be concluded that NS of MCP HCl
      represents a viable approach to achieving rapid and high systemic drug absorption
      during the emergency treatment of severe emesis.

PMID- 16959454
TI  - Treatment of THP-1 cells with Uncaria tomentosa extracts differentially regulates
      the expression if IL-1beta and TNF-alpha.
AB  - Uncaria tomentosa, commonly known as cat's claw, is a medicinal plant native to
      Peru, which has been used for decades in the treatment of various inflammatory
      disorders. Uncaria tomentosa can be used as an antioxidant, has anti-apoptotic
      properties, and can enhance DNA repair, however it is best know for its anti
      inflammatory properties. Treatment with Uncaria tomentosa extracts inhibits the
      production of the pro-inflammatory cytokine, TNF-alpha, which is a critical
      mediator of the immune response. In this paper, we showed that treatment of THP-1
      monocyte-like cells with Uncaria tomentosa extracts inhibited the MAP kinase
      signaling pathway and altered cytokine expression. Using ELISA assays, we showed
      that treatment with Uncaria tomentosa extracts augmented LPS-dependent expression
      of IL-1beta by 2.4-fold, while inhibiting the LPS-dependent expression of TNF
      alpha by 5.5-fold. We also showed that treatment of LPS-stimulated THP-1 cells
      with Uncaria tomentosa extracts blocked ERK1/2 and MEK1/2 phosphorylation in a
      dose-dependent manner. These data demonstrate that treatment of THP-1 cells with
      Uncaria tomentosa extracts has opposite effects on IL-1beta and TNF-alpha
      secretion, and that these changes may involve effects on the MAP kinase pathway.

PMID- 16959457
TI  - Why aging isn't regulated: a lamentation on the use of language in aging
      literature.
AB  - Aging research has a problem. The field is expanding rapidly but our
      understanding of aging is clouded because of the language we use when describing
      genes that influence aging. As researchers from different disciplines gather to
      solve aging problems, different terms are being used to describe genetic affects.
      Genetic alterations can bring about enormous changes in lifespan but the
      significance of these experiments is debated; either the results are hailed as
      spectacular breakthroughs or alternatively considered laboratory artifacts
      unlikely to reveal useful knowledge about aging. How could this have come about
      and what do we need to do about it? I suggest we need to listen to exactly what
      each other is saying and also think carefully about how we are using key terms
      when describing our results. Rather than a scholarly review of this important
      issue, this article is intended to prompt debate. Consequently, "the gloves are
      off".

PMID- 16959458
TI  - Imaging neonates--special paediatric edition 2006.

PMID- 16959460
TI  - Imaging of the neonatal genito-urinary tract.
AB  - OBJECTIVE: To describe imaging of typical conditions and diseases in the neonatal
      genito-urinary (GU) tract. METHOD: The use, the applications, and typical
      findings using standard imaging techniques (e.g., ultrasound, US, voiding
      cystourethrography, VCUG) are described, with emphasis on technical aspects,
      indications, and restrictions in neonatal queries. Only basic applications as
      used in routine clinical work are included, other more sophisticated and advanced
      imaging techniques such as scintigraphy, MR-urography, genitography or image
      guided interventional procedures will only briefly be mentioned. SUMMARY AND
      CONCLUSION: Conventional imaging methods are valuable and - particularly in the
      neonatal GU tract - sometimes irreplaceable. Skillfully used basic imaging
      techniques, particularly of US (including modern methods such as Doppler
      sonography, Harmonic imaging or contrast enhanced US), supplemented by
      fluoroscopy for VCUG can answer most acutely treatment relevant queries. Rarely
      early scintigraphic studies, genitography, or MRI may become indicated, usually
      not for establishing the diagnosis, but to collect additional (functional or
      anatomical) information necessary for deciding on further treatment, or even
      image guided interventional procedures may become necessary.

PMID- 16959461
TI  - Does a stable isotopically labeled internal standard always correct analyte
      response? A matrix effect study on a LC/MS/MS method for the determination of
      carvedilol enantiomers in human plasma.
AB  - A stable isotopically labeled (SIL) analogue is believed to be the most
      appropriate internal standard in a quantitative bioanalytical liquid
      chromatography/tandem mass spectrometry (LC/MS/MS) assay. It is assumed that a
      SIL internal standard always compensates for variability in chemical
      derivatization, sample extraction and LC/MS/MS analysis due to its nearly
      identical chemical and physical properties to the unlabeled analyte. Hence, the
      analyte to internal standard peak area ratio should be constant despite any
      variations in sample processing or analysis. However, in our laboratories, a
      deuterium labeled internal standard of carvedilol demonstrated an unexpected
      behavior-the analyte to internal standard peak area ratio changed with two
      specific lots of commercially supplied human plasma. Several experiments,
      including dilution of the extract with LC mobile phase and post-column infusion
      of the carvedilol solution followed by the injection of extracted blank plasma,
      have indicated that a high level of matrix suppression affected the ionization of
      the carvedilol-S enantiomer and its deuterated internal standard differently in
      these two lots of plasma. For the first time, it was clearly demonstrated that a
      slight difference in retention time between the analyte and the SIL internal
      standard, caused by deuterium isotope effect, has resulted in a different degree
      of ion suppression between these two analogues. This difference was significant
      enough to change the analyte to internal standard peak area ratio and affect the
      accuracy of the method.

PMID- 16959462
TI  - ICH guidance in practice: validated stability-indicating HPLC method for
      simultaneous determination of ampicillin and cloxacillin in combination drug
      products.
AB  - Ampicillin and cloxacillin were degraded together under different stress test
      conditions prescribed by International Conference on Harmonization. The samples
      so generated were used to develop a stability-indicating high performance liquid
      chromatographic (HPLC) method for the two drugs. The drugs were well separated
      from degradation products using a reversed-phase (C-18) column and a mobile phase
      comprising of acetonitrile:phosphate buffer (pH 5.0), which was delivered
      initially in the ratio of 15:85 (v/v) for 1 min, then changed to 30:70 (v/v) for
      next 14 min, and finally equilibrated back to 15:85 (v/v) from 15 to 20 min.
      Other HPLC parameters were: flow rate, 1 ml/min; detection wavelength, 225 nm;
      and injection volume, 5 microl. The method was validated for linearity,
      precision, accuracy, specificity and selectivity. It was also compared with the
      assay procedures given in British Pharmacopoeia for individual drugs. Similar
      results were obtained, indicating that the proposed single method allowed
      selective analysis of both ampicillin and cloxacillin, in the presence of their
      degradation products formed under a variety of stress conditions. The developed
      procedure was also applicable to the determination of instability of the drugs in
      commercial products.

PMID- 16959464
TI  - RETRACTED: Simultaneous determination of alkaloids, diterpenoids and steroids in
      Jin-Guo-Lan by high performance liquid chromatography (HPLC-DAD) method.
AB  - This article has been retracted consistent with Elsevier Policy on Article
      Withdrawal. Please see . The Publisher apologizes for any inconvenience this may
      cause.

PMID- 16959463
TI  - Development and validation of a high performance liquid chromatographic method
      for the determination of oxcarbazepine and its main metabolites in human plasma
      and cerebrospinal fluid and its application to pharmacokinetic study.
AB  - An isocratic reversed-phase HPLC-UV procedure for the determination of
      oxcarbazepine and its main metabolites 10-hydroxy-10,11-dihydrocarbamazepine and
      10,11-dihydroxy-trans-10,11-dihydrocarbamazepine in human plasma and
      cerebrospinal fluid has been developed and validated. After addition of
      bromazepam as internal standard, the analytes were isolated from plasma and
      cerebrospinal fluid by liquid-liquid extraction. Separation was achieved on a X
      TERRA C18 column using a mobile phase composed of 20 mM KH(2)PO(4), acetonitrile,
      and n-octylamine (76:24:0.05, v/v/v) at 40 degrees C and detected at 237 nm. The
      described assay was validated in terms of linearity, accuracy, precision,
      recovery and lower limit of quantification according to the FDA validation
      guidelines. Calibration curves were linear with a coefficient of variation (r)
      greater than 0.998. Accuracy ranged from 92.3% to 106.0% and precision was
      between 2.3% and 8.2%. The method has been applied to plasma and cerebrospinal
      fluid samples obtained from patients treated with oxcarbazepine, both in
      monotherapy and adjunctive therapy.

PMID- 16959465
TI  - Effect of pinealectomy and melatonin replacement on morphological and biochemical
      recovery after traumatic brain injury.
AB  - Numerous studies showed that melatonin, a free radical scavenger, is
      neuroprotective. In this study, we investigated the effect of pinealectomy and
      administration of exogenous melatonin on oxidative stress and morphological
      changes after experimental brain injury. The animals were divided into six
      groups, each having 12 rats. Group 1 underwent craniotomy alone. Group 2
      underwent craniotomy followed by brain trauma and received no medication. Group 3
      underwent craniotomy followed by brain trauma and received melatonin. Group 4
      underwent pinealectomy and craniotomy alone. Group 5 underwent pinealectomy and
      craniotomy followed by brain injury and received no medication. Group 6 underwent
      pinealectomy and craniotomy followed by brain trauma and received melatonin.
      Melatonin (100 mg/kg) was given intraperitoneally immediately after trauma to the
      rats in Groups 3 and 6. Pinealectomy caused a significant increase in the
      malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH), and xanthine oxidase
      (XO) levels, and a decrease in GSH levels as compared to the control group.
      Trauma to pinealectomized rats causes significantly higher oxidative stress.
      Exogeneous melatonin administration significantly reduced MDA, XO and NO levels,
      increased GSH levels, and attenuated tissue lesion area. These findings suggest
      that reduction in endogenous melatonin after pinealectomy makes the rats more
      vulnerable to trauma, and exogenous melatonin administration has an important
      neuroprotective effect.

PMID- 16959466
TI  - Video information combined with individualized information sessions: Effects upon
      emotional well-being following coronary artery bypass surgery--A randomized
      trial.
AB  - OBJECTIVE: To test the efficacy of an information intervention upon emotional
      recovery following coronary artery bypass surgery. METHODS: Randomized trial.
      Video information was combined with individualized information sessions carried
      out by nurses at admission and at discharge from the hospital. The video was
      shown pre-operatively and again during the session at admission. Patients were
      helped to express their questions and worries and congruent information and
      support was provided. Control group patients received standardized information
      and no video. Recordings were made at baseline, discharge from hospital and
      during a 2 years follow-up period. RESULTS: One hundred and nine patients were
      randomized to the intervention or the control groups. A MANOVA was used to test
      of the variance of the outcome variables at each time point. At discharge
      intervention patients reported less anxiety (p = 0.046) and better subjective
      health (p = 0.005). They reported better subjective health during the whole
      follow-up period (0.040 > or = p > or = 0.000), less anxiety up to 1 year (0.042
      > or = p > or = 0.004), and less depression from 6 months to 2 years following
      discharge (0.023 > or = p > or = 0.004). CONCLUSION: The effects of the
      intervention probably relate to the combined use of the video and patient
      centered information sessions. PRACTICE IMPLICATIONS: The intervention can easily
      be implemented in clinical practice and nurses strongly identified with its
      principles.

PMID- 16959467
TI  - Serum thyroglobulin measurement: clinical background and main methodological
      aspects with clinical impact.
AB  - It is worldwide recognized that circulating thyroglobulin (Tg) measurement
      represents a fundamental tool in the follow-up of patients affected by
      differentiated thyroid cancer (DTC). In the last American and European Consensus
      Conferences, a surveillance guideline has been extended to the use of thyrotropin
      (TSH)-stimulated Tg levels for thyroidectomized patients without clinical
      evidence of residual tumor with Tg below 1 microg/l during TSH suppression.
      Therefore, sensitivity of the methods is critical to detect small amounts of Tg
      and/or to observe minimal changes in Tg concentration in the management of DTC
      patients. It has been proposed that only methods providing the greatest
      distinction between the lower limit of euthyroid reference range (approximately
      3.0 microg/l) and the functional sensitivity limit (at least 1 microg/l) of the
      assay may offer a suitable clinical sensitivity for detecting small amounts of
      functioning thyroid tissue in TSH-suppressed state (1 g of normal thyroid tissue
      results in a serum Tg of approximately 1 microg/l when TSH is normal and about
      0.5 microg/l when TSH is suppressed). In the last 30 years sensitivity of Tg
      measurements has been greatly improved, nowadays methods can achieve very good
      analytical and functional sensitivity to give reliable results also in the very
      low concentration range (between 0.1 and 1 microg/l). In addition, with the
      introduction of fully automated assays, results can be readily available to the
      clinician while patients are still in the ambulatory area. However, despite the
      large clinical use of Tg measurement, wide differences (by threefold) still
      remain between results produced in different laboratories due to poor
      standardization, heterogeneity of circulating Tg, interference from auto
      antibodies, differences in the epitope recognition by antibodies used in the
      assays.

PMID- 16959469
TI  - Isolation, expression, and characterization of the human ZCRB1 gene mapped to
      12q12.
AB  - While isolating morphine-dependence-related genes with differential display, we
      cloned a novel human gene, zinc finger CCHC-type and RNA-binding motif 1 (ZCRB1,
      alias MADP-1) encoding a nuclear protein (217 residues). The ZCRB1 gene consists
      of eight exons and seven introns. It is mapped to 12q12, which is within a locus
      reported for Parkinson disease (M. Funayama et al., Ann. Neurol. 51 (2002) 296
      301). The 5'-flanking region contains an enhancer core motif and binding sites
      for AP-1, AP-2, and LF-A1. ZCRB1 is characterized by an RNA-binding motif and a
      CCHC zinc finger motif. The latter overlaps the C..C...GH....C core nucleocapsid
      motif. ZCRB1 is conserved from zebrafish to human and shares homology with cold
      inducible RNA-binding protein. Transfection assay showed that ZCRB1 is located in
      the nucleoplasm, but outside the nucleolus. ZCRB1 gene expression was stimulated
      by morphine, inhibited by 30-36 degrees C, and up-regulated by 39 degrees C
      incubation in SH-SY5Y neural cells. Zcrb1 gene expression is highest in the heart
      and testes, lower in the cerebellum, and lowest in the liver in mice. ZCRB1 mRNA
      expression is specifically elevated in hepatocarcinoma HepG2 cells. These data
      provide new clues for further understanding of morphine dependence, heat shock,
      and hepatocarcinoma.

PMID- 16959468
TI  - Evaluation of a proposed in vitro test strategy using neuronal and non-neuronal
      cell systems for detecting neurotoxicity.
AB  - The European Commission White Paper, "Strategy for a future chemicals policy"
      (EC, 2001) is estimated to require the testing of approximately 30,000 "existing"
      chemicals by 2012. Recommended in vitro tests require validation. As the White
      Paper (EC, 2001) requires neurotoxic data, this study evaluated an in vitro
      testing strategy for predicting in vivo neurotoxicity. The sensitivities of
      differentiated PC12 cells and primary cerebellum granule cells (CGC) were
      compared to undifferentiated PC12 cells which can indicate basal cytotoxicity.
      Cytotoxicants and neurotoxicants selected for testing covered a range of
      mechanisms and potencies. Neurotoxicants were not distinguished from
      cytotoxicants despite significantly different cell system responses using all
      endpoints; cell viability/activity, ATP depletion, MMP depolarisation, ROS
      production and cytoskeleton modifications. For all chemicals tested, neuronal
      like cell systems were generally less sensitive than undifferentiated PC12 cells.
      Acute oral rodent LD(50) values correlated with cytotoxicity IC(50) values for
      the respective chemicals tested in each cell system. This study concluded that
      although simple non-specific assays are required to distinguish basal
      cytotoxicity from specific neurotoxicity by using different cell systems with
      different states of neuronal differentiation, further work is required to
      determine suitable combinations of cell systems and endpoints capable of
      distinguishing neurotoxicants from cytotoxicants.

PMID- 16959470
TI  - In vivo and in vitro investigations of the effects of the antimalarial drug
      dihydroartemisinin (DHA) on rat embryos.
AB  - Artemisinin derivatives are clinically effective and safe antimalarials, but are
      not recommended during the first trimester of pregnancy because of the
      resorptions and abnormalities seen in animal reproduction studies. Understanding
      how, when and what toxicity occurs is crucial to any assessment of clinical
      relevance. Previously, DHA has been shown in the rat whole embryo culture (WEC)
      to primarily affect primitive red blood cells (RBCs) causing subsequent tissue
      damage and dysmorphogenesis. To verify the primary target of DHA in vivo and to
      detect consequences induced by early damage on embryo development, pregnant
      female rats were orally treated on gestation days (GD) 9.5 and 10.5 with 7.5 or
      15 mg/kg/day DHA and caesarean sectioned on GD11.5, 12.5, 13.5, 15 and 20. A
      parallel in vitro WEC study evaluated the role of oxidative damage and examined
      blood islands and primitive RBCs. In accordance with the WEC results, primitive
      RBCs from yolk sac hematopoiesis were the target of DHA in vivo. The resulting
      anemia led to cell damage, which depending on its degree, was either diffuse or
      focal. Embryonic response to acute anemia varied from complete recovery to
      malformation and death, depending on the extent of cell death. Malformations
      occurred only in litters with embryonic deaths. DHA induced low glutathione
      levels in RBCs, indicating that oxidative stress may be involved in artemisinin
      toxicity; effects were extremely rapid, with altered RBCs seen as early as GD10.
      In establishing the relevance of these findings to humans, one should consider
      differences in the development of rodents and humans. While yolk sac
      hematopoiesis occurs similarly in the two species, early placentation and extent
      of exposure differ. In particular, early hematopoiesis takes only 7 days in rats
      (during which RBCs expand in a clonal fashion) compared with 6 weeks in humans;
      thus the susceptible period in relation to the duration of exposure to an
      artemisinin-based treatment may be substantially different.

PMID- 16959471
TI  - Chlorinative stress: an under appreciated mediator of neurodegeneration?
AB  - Oxidative stress has been implicated as playing a role in neurodegenerative
      disorders, such as ischemic stroke, Alzheimer's, Huntington's, and Parkinson's
      disease. Persuasive evidences have shown that microglial-mediated oxidative
      stress contributes significantly to cell loss and accompanying cognitive decline
      characteristic of the diseases. Based on the facts that (i) levels of
      catalytically active myeloperoxidase are elevated in diseased brains and (ii)
      myeloperoxidase polymorphism is associated with the risk of developing
      neurodegenerative disorders, HOCl as a major oxidant produced by activated
      phagocytes in the presence of myeloperoxidase is therefore suggested to be
      involved in neurodegeneration. Its association with neurodegeneration is further
      showed by elevated level of 3-chlorotyrosine (bio-marker of HOCl in vivo) in
      affected brain regions as well as HOCl scavenging ability of neuroprotectants,
      desferrioxamine and uric acid. In this review, we will summary the current
      understanding concerning the association of HOCl and neuronal cell death where
      production of HOCl will lead to further formation of reactive nitrogen and oxygen
      species. In addition, HOCl also causes tissue destruction and cellular damage
      leading cell death.

PMID- 16959472
TI  - Beneficial effects of ondansetron as an adjunct to haloperidol for chronic,
      treatment-resistant schizophrenia: a double-blind, randomized, placebo-controlled
      study.
AB  - BACKGROUND: Previous studies suggest that the serotonin-3 (5-HT3) receptor
      antagonist ondansetron possesses the therapeutic potential for schizophrenia.
      This study was designed to determine whether ondansetron as an adjunct to
      haloperidol could enhance the clinical efficacy and reduce the adverse side
      effects in chronic treatment-resistant schizophrenia. METHODS: Under double
      blind, randomized conditions, 121 treatment-resistant inpatients with chronic DSM
      IV-diagnosed schizophrenia received haloperidol (4-30 mg/day) combined with
      either placebo (N=63) or a fixed dose of 8 mg/day of ondansetron (N=58) for 12
      weeks. Efficacy was defined as the change from baseline to endpoint in score on
      overall scale and subscales of the Positive and Negative Syndrome Scale (PANSS)
      and Clinical Global Impression-Severity (CGI-S). Side effects were evaluated
      using the Treatment Emergent Symptom Scale and Extrapyramidal Symptom Rating
      Scale. RESULTS: Ondansetron combined with haloperidol produced a significantly
      greater improvement on PANSS overall scale and subscales for negative symptoms,
      general psychopathology, and cognition at endpoint compared to placebo with
      haloperidol, but no between-treatment group difference was observed on the
      subscale for positive symptoms and CGI-S. The ondansetron-treated group had a
      significantly higher proportion of patients with a 30% or greater baseline-to
      endpoint reduction in PANSS total score than placebo. Patients in adjunctive
      ondansetron therapy also experienced significantly lower incidence and severity
      of parkinsonism and akathisia as well as fewer behavioral hyperactivity, cardiac,
      and gastrointestinal side effects. CONCLUSIONS: Ondansetron is an effective
      adjunctive agent in enhancing the effectiveness and reducing some adverse side
      effects of antipsychotic therapy for chronic, treatment-resistant schizophrenia,
      particularly for negative and cognitive symptoms.

PMID- 16959473
TI  - Secretory aspartyl peptidase activity from mycelia of the human fungal pathogen
      Fonsecaea pedrosoi: effect of HIV aspartyl proteolytic inhibitors.
AB  - Fonsecaea pedrosoi is the principal causative agent of chromoblastomycosis, which
      is a chronic, often debilitating, suppurative and granulomatous mycosis. Very
      little is known about the hydrolytic enzymes produced by this human fungal
      pathogen. In the present study, we have identified extracellular proteolytic
      activity from F. pedrosoi mycelial forms when grown in chemically defined
      conditions. Secretory aspartyl peptidase activity was measured during 15 days of
      fungal growth in vitro using bovine serum albumin (BSA) as the soluble substrate
      and extreme acidic pH (2.0). This activity was totally inhibited by pepstatin A,
      a classic aspartyl peptidase inhibitor. Conversely, metallo (o-phenanthroline),
      cysteine (E-64) and serine (PMSF) proteolytic inhibitors failed to restrain
      proteolytic activity. We also evaluated the effect of four distinct HIV aspartyl
      peptidase inhibitors on the secretory proteolytic activity of F. pedrosoi
      mycelia. Indinavir, ritonavir and nelfinavir powerfully inhibited extracellular
      aspartyl proteolytic activity by approximately 97, 96 and 87%, respectively,
      whereas saquinavir did not significantly interfere with BSA hydrolysis. Mycelial
      derived secretory aspartyl peptidase activity cleaved other proteinaceous
      substrates, including human albumin, fibrinogen, fibronectin, laminin and type I
      collagen. As previously reported by our group, conidia also produce secretory
      aspartyl peptidase. In this sense, we investigated the effect of pepstatin A on
      F. pedrosoi development. Pepstatin A was able to inhibit the growth of conidium
      and its transformation into mycelium. Taken together, our results suggest a
      possible participation of aspartyl peptidases in the essential fungal processes,
      such as growth, differentiation, nutrition and cleavage of relevant host
      proteinaceous components.

PMID- 16959474
TI  - Left temporal perfusion associated with suspiciousness score on the Brief
      Psychiatric Rating Scale in schizophrenia.
AB  - We evaluated the relationship between regional cerebral blood flow (rCBF) and
      clinical symptoms in patients with schizophrenia. Single photon emission computed
      tomography with N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) was used to study
      29 patients with schizophrenia. Clinical symptoms were assessed using the Brief
      Psychiatric Rating Scale (BPRS). We examined the correlation between rCBF and
      each BPRS item score using Statistical Parametric Mapping software. Corrected P
      values < 0.05 were considered as statistically significant. The suspiciousness
      score on the BPRS was positively correlated with rCBF in the left inferior
      temporal gyrus. There was no significant correlation between rCBF and any other
      items of the BPRS. There was no significant correlation between rCBF and
      chlorpromazine-equivalent dosage. This analysis permits the quantitative
      assessment of the severity of persecutory delusions in relation to left temporal
      perfusion in patients with schizophrenia.

PMID- 16959475
TI  - Relationships between characteristics of interfacial water and human bone
      tissues.
AB  - Water bound in human bone tissues healthy (sample S1) and affected by
      osteoporosis (sample S2) was investigated by using 1H NMR spectroscopy with layer
      by-layer freezing-out of bulk and interfacial waters at T< 273 K. The 1H NMR
      spectra of the bound water include two signals which can be assigned to strongly
      associated typical water (chemical shift of the proton resonance at delta(H)
      approximately 5 ppm) and weakly associated water at delta(H) approximately 1.4
      ppm. Approximately, half of the bound water is in the weakly associated state in
      S1. A fraction of similar water in S2 is smaller because of the structural
      difference of the studied samples. The pore size distribution of S2 (in aqueous
      medium) calculated using the cryoporometry method is characterized by much larger
      intensity of mesopores and macropores in comparison with that of S1. The total
      porosity and the surface area of the biostructures (accessible for water
      molecules and estimated on the basis of the cryoporometry data using a model of
      cylindrical pores) are larger for S2. Weakly polar chloroform-d has a significant
      influence on the organization of water in a spongy component of bone tissue. This
      effect depends on the porosity of the bone matrix and the amounts of CDCl3.

PMID- 16959476
TI  - [Effects of nasal continuous positive airway pressure ventilation in infants with
      severe acute bronchiolitis].
AB  - OBJECTIVE: Usefulness of nasal continuous positive airway pressure (NCPAP) in
      severe acute bronchiolitis has been checked. The objective of this descriptive
      study was to evaluate the feasibility, safety and risk factors of NCPAP failure.
      POPULATION AND METHODS: One hundred and forty-five infants were hospitalised in
      our intensive care unit during the 2 last epidemics (2003-2004, 2004-2005). Among
      them, 121 needed a respiratory support, either invasive ventilation (N=68) or
      NCPAP (N=53). RESULTS: General characteristics were similar during the 2 periods.
      Percentage of NCPAP failure, defined by tracheal intubation requirement during
      the stay in paediatric intensive care unit, was quite similar during the 2
      periods (25%), but number of NCPAP increased twofold. Whatever the evolution was
      in the NCPAP group, we observed a significant decrease in respiratory rate (60+/
      16 vs 47.5+/-13.7 cycle/min., P<0.001) and PaCO2 (64.3+/-13.8 vs 52.6+/-11.7
      mmHg, P=0.001) during NCPAP. Only PRISM calculated at day 1 and initial reduction
      of PaCO2 were predictive of NCPAP failure. Percentage of ventilator associated
      pneumonia was similar (22%) between the invasive ventilation group and infants
      who where intubated because of failure of NCPAP. Duration of respiratory support
      and stay were reduced in the NCPAP group (P<0.002). CONCLUSION: NCPAP appears to
      be a safe alternative to immediate intubation in infants with severe
      bronchiolitis.

PMID- 16959477
TI  - Postprandial responses in the African rhombig egg eater (Dasypeltis scabra).
AB  - The African rhombic egg eater (Dasypeltis scabra) is a colubrid snake feeding
      exclusively on bird eggs. Frequency of feeding is governed by the seasonal
      availability of bird eggs; i.e., long fasting intervals change with relatively
      short periods when plenty of food is available. Intermittent feeding snakes show
      a remarkable postprandial increase of metabolic rate and digestive organ size.
      The postprandial increase in metabolic rate (specific dynamic action, SDA) in
      snakes is affected by meal size, temperature, and meal composition. A major
      portion of SDA in snakes is allocated to gastric function and the breakdown of
      the meal. We hypothesize that SDA in egg eaters is lower than in other snake
      species, because egg eaters feed on "liquid" food that does not require enzymatic
      breakdown in the stomach. We also hypothesized that other components of the
      postprandial response of egg eaters (e.g., size changes of the intestine and the
      liver) do not differ from other snakes. The standard metabolic rate and metabolic
      response to feeding were measured using closed-chamber respirometry. Size changes
      of small intestine and liver were measured using high-resolution transcutaneous
      ultrasonography. Standard metabolic rates of fasting egg eaters were in the same
      range of mass specific values as known from other snakes. Within 24h after
      feeding, oxygen consumption doubled and peaked at 2 days after feeding. At the
      same time, the size of the small intestine and the cross-sectional diameter of
      the liver increased. Within 2 days after feeding, the size of the mucosal
      epithelium doubled its thickness. Liver size increased significantly within 24h
      reaching maximum size 2-4 days after feeding. The size of both organs returned to
      fasting values within 7-10 days after feeding. The postprandial response of
      African rhombic egg eaters shows the same pattern and dynamics as known from
      other snake species. However, the factorial increase of metabolic rate during SDA
      is the lowest reported for any snake. A comparison with literature data supports
      the idea that SDA is mainly determined by gastric function and that it is low in
      egg eaters because they do not have to break down solid meals in the stomach as
      other snake species do.

PMID- 16959478
TI  - Thielavia gigaspora, a new thermotolerant ascomycete from Egypt.
AB  - Thielavia gigaspora sp. nov. from herbivore dung is described and illustrated.
      The new taxon by comparison with previously known species is distinguished by
      relatively large ascospores (25-38 x 15-21 microm), each showing an apical,
      protuberant germ pore and a longitudinal dark band. A brief comparison with
      morphologically related species is given.

PMID- 16959479
TI  - Influence of phenolics on the sensitivity of free and immobilized bioluminescent
      Acinetobacter bacterium.
AB  - In this work, the constructed bioluminescent Acinetobacter strain DF4/PUTK2 was
      employed to assess the toxicity of phenolic compounds and the 5 min EC50 values
      were calculated. The results of the DF4/PUTK2 assay were further evaluated by
      comparing with the results of the Vibrio fischeri luminescence inhibition assay.
      To develop a bioassay system appropriate to be used in continuous toxicity
      testing, strain DF4/PUTK2 was subjected for immobilization in microtiter plates
      into the matrices Ca-alginate, polyacrylamide, agar and agarose. After a choice
      of materials was tried, Ca-alginate was selected as the most suitable candidate
      material. Because, it could be stored at least 8 weeks at 4 degrees C, during
      which the ability of the bioreporter DF4/PUTK2 to detect the toxicity of
      phenolics was maintained. However, the stability of the bioluminescence for
      DF4/PUTK2 cells immobilized into agarose and agar was significantly less than
      that of cells stored in alginate suspensions. This study recommended that
      luxCDABE-marked Acinetobacter strain DF4/PUTK2 could be employed to assay the
      ecotoxicity of environmental samples contaminated with phenols. The host strain
      of the bioreporter DF4/PUTK2 is Acinetobacter strain DF4. It is known that
      members of the genus Acinetobacter are widespread in nature and also involved in
      biodegradation, leaching and removal of several organic and inorganic man-made
      hazardous wastes.

PMID- 16959480
TI  - Long-term incomplete xylose fermentation, after glucose exhaustion, with Candida
      shehatae co-immobilized with Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae and Candida shehatae were co-immobilized in an agar
      sheet which was introduced in an original two-chambered bioreactor asymmetrically
      fed in a batch mode with a mixture of glucose and xylose in a ratio of 35:15. The
      two sugars were consumed simultaneously. All glucose was fermented but only 20%
      of xylose. After incubation, yeast cells recovered from different areas of the
      agar sheet (close to, called Hi, and distant from, called Ho, the substrate
      chamber) were cultured as suspended cells in fresh culture medium provided with
      xylose or the sugar mixture. Xylose utilization by gel released Hi yeasts was
      significantly delayed compared to the Ho culture. Ethanol consumption by Hi
      yeasts in the two-substrate medium occurred after glucose exhaustion despite the
      presence of xylose. The waste medium resulting from incubation of the immobilized
      cell structure inhibited xylose utilization by C. shehatae. Our results suggested
      that batch fermentation most probably favoured this incomplete xylose
      fermentation.

PMID- 16959482
TI  - Fatty acid composition of lipids from mushrooms belonging to the family
      Boletaceae.
AB  - The non-polar lipid content and fatty acid (FA) composition of 11 mushroom
      species of the family Boletaceae were determined. The non-polar lipid content
      ranged from 2.0 (Leccinum aurantiacum and Boletus erythropus) to 5.4 % (w/w) d.w.
      (Suillus grevillei) with an average value of 2.9 %. More than 25 different FAs
      were found in the mushroom lipids. Unsaturated FAs, mainly linoleic and oleic
      acids, accounted for about 83 % of the total FAs, while palmitic acid was the
      main saturated FA. Some FAs are identified for the first time in Boletaceae and
      in higher Basidiomycetes (cis-11,12-methyleneoctadecanoic acid, 7-cis,10-cis
      hexadecadienoic) or in fungi (cis-11,12-methyleneoctadecanoic acid). There were
      significant differences (P<0.05) in the contents of specific FAs between mushroom
      species.

PMID- 16959481
TI  - Relationship between omega-3 fatty acids and plasma neuroactive steroids in
      alcoholism, depression and controls.
AB  - Deficiency in the long-chain omega-3 fatty acid, docosahexaenoic acid (DHA) has
      been associated with increased corticotropin releasing hormone and may contribute
      to hypothalamic pituitary axis (HPA) hyperactivity. Elevated levels of the
      neuroactive steroids, allopregnanolone (3alpha,5alpha-THP) and 3alpha,5alpha
      tetrahydrodeoxycorticosterone (THDOC) appear to counter-regulate HPA
      hyperactivity. Plasma essential fatty acids and neurosteroids were assessed among
      18 male healthy controls and among 34 male psychiatric patients with DSM-III
      alcoholism, depression, or both. Among all subjects, lower plasma DHA was
      correlated with higher plasma THDOC (r = -0.3, P < 0.05) and dihydroprogesterone
      (DHP) (r = -0.52, P < 0.05). Among psychiatric patients lower DHA was correlated
      with higher DHP (r = -0.60, P < 0.01), and among healthy controls lower plasma
      DHA was correlated with higher THDOC (r = -0.83, P < 0.01) and higher
      isopregnanolone (3beta,5alpha-THP) (r = -0.55, P < 0.05). In this pilot
      observational study, lower long-chain omega-3 essential fatty acid status was
      associated with higher neuroactive steroid concentrations, possibly indicating
      increased feedback inhibition of the HPA axis.

PMID- 16959483
TI  - Electrochemical impedance detection of DNA hybridization based on dendrimer
      modified electrode.
AB  - Bioactive ultrathin films with the incorporation of amino-terminated G4 PAMAM
      dendrimers have been prepared via layer-by-layer self-assembly methods on a gold
      electrode and used for the DNA hybridization analysis. Surface plasmon resonance
      (SPR), X-ray photoelectron spectroscopy (XPS), and electrochemical impedance
      spectroscopy (EIS) are used to characterize the successful construction of the
      multicomponent film on the gold substrate. The dendrimer-modified surfaces
      improve the immobilization capacity of the probe DNA greatly, compared to the AET
      (2-aminoethanethiol) SAM sensor surfaces without dendrimer molecules. DNA
      hybridization analysis is monitored by EIS. The dendrimer-based electrochemical
      impedance DNA biosensor shows high sensitivity and selectivity for DNA
      hybridization assay. The multicomponent films also display a high stability
      during repeated regeneration and hybridization cycles.

PMID- 16959484
TI  - 2D aggregation and selective desorption of nanoparticle probes: a new method to
      probe DNA mismatches and damages.
AB  - A 2D colorimetric DNA sensor is reported based on the 2D aggregation of
      oligonucleotide-modified gold nanoparticle probes resulting from the molecular
      hybridization between these latest and their complementary single stranded DNA
      targets. To increase their mobility the nanoparticles are adsorbed on a fluid
      lipid bilayer, itself supported on a substrate. The hybridization between the
      target and the mobile nanoparticle probes creates links between the nanoparticles
      resulting in the formation of nanoparticle aggregates in the plane of the
      substrate. This aggregation is detected using a new method based on the selective
      desorption of non-aggregated nanoparticles. The addition of dextran sulfate
      induces the substitution of non-aggregated gold nanoparticles while aggregated
      ones are stable on the substrate. We show that this detection method is highly
      specific and allows the detection of DNA mismatches and damages.

PMID- 16959485
TI  - Overexpression of a member of the pentraxin family (PTX3) in human soft tissue
      liposarcoma.
AB  - A unique feature of human soft tissue liposarcoma is a stable (12;16)(q13;p11)
      translocation observed mainly in myxoid and roundcell liposarcomas. This
      translocation results in FUS/CHOP fusion transcripts with a corresponding
      oncogenic protein. We hypothesised that genes downstream of FUS/CHOP might serve
      as attractive candidates for novel tumour associated antigens. Among a panel of
      analysed genes, only pentraxin related gene (PTX3) demonstrated high expression
      in liposarcomas as compared to normal tissues. The analysis of RNA and protein
      expression demonstrated concordant results. However, the level of RNA and protein
      overexpression did not correlate in all cases. Finally, PTX3 expression was not
      related to presence of a FUS/CHOP fusion transcript within the liposarcoma
      tissues. PTX3 has been associated with adipocyte differentiation and now,
      additionally, is characterised by a markedly increased expression in human soft
      tissue liposarcoma. This finding mandates further research efforts to clarify the
      exact role of PTX3 in liposarcoma oncogenesis.

PMID- 16959486
TI  - Long term morbidity and health related quality of life after multi-system
      Langerhans cell histiocytosis.
AB  - BACKGROUND: Langerhans' cell histiocytosis, a clonal multisystem disorder, can
      affect children or adults resulting in long term sequelae. However, the overall
      morbidity for survivors has not been formally determined. PATIENTS AND METHODS:
      We performed a cross-sectional study of 40 unselected long term survivors of
      childhood multisystem Langerhans cell histiocytosis, involving clinical
      examination, health-related quality of life assessment, brain imaging,
      neuropsychometry, endocrine assessment, respiratory function tests and
      audiometry. A specific 'morbidity score' was devised to measure outcome. RESULTS:
      Seventy-five percent of patients had detectable long term sequelae, hypothalamic
      pituitary dysfunction (50%), cognitive dysfunction (20%) and cerebellar
      involvement (17.5%) being the most common. Half had moderate to severe morbidity,
      and the worst-affected patients were unable to lead an independent adult life.
      Health-related quality of life, which correlated well with the morbidity score
      (p<0.001), was adversely affected in >50% of patients. CONCLUSION: Organ damage
      from multisystem Langerhans cell histiocytosis causes long term morbidity
      extending into adult life. Carefully planned, multidisciplinary follow up is
      essential to ensure early recognition of problems with appropriate interventions
      to reduce the impact on patients' 'quality of life'.

PMID- 16959487
TI  - Synthesis and SAR of novel hydantoin derivatives as selective androgen receptor
      modulators.
AB  - A novel series of hydantoin derivatives were identified by in vivo studies as
      tissue selective androgen receptor modulators. SAR around this series revealed
      that the function of the ligand could be altered by minor structural
      modification.

PMID- 16959488
TI  - Age-related differences in spatiotemporal markers of gait stability during dual
      task walking.
AB  - Increased stride-to-stride variability during walking characterizes gait
      instability and predicts falling in older adults. Walking while performing
      cognitive tasks (dual task walking) is also associated with increased risk of
      falling. The purpose of the study was to examine whether gait velocity and stride
      to-stride variability in gait velocity differ in older adults compared with
      middle-aged and younger adults during normal and dual task walking conditions.
      Sixty older (n=20, mean age=81 years), middle-aged (n=20, mean age=48 years), and
      young adults (n=20, mean age=25 years) participated in the study. Gait parameters
      were quantified with GAITRite instrumentation. In the dual task condition,
      participants spelled five-letter words in reverse while walking across the
      walkway. Across groups, gait velocity was slower (p<0.001) and stride-to-stride
      variability in gait velocity was greater (p=0.001) in dual task walking. Older
      subjects walked more slowly than did middle-aged and younger subjects and the
      difference in gait velocity was greatest in the dual task condition (p<0.05).
      Variability in stride velocity was increased in older subjects compared with
      middle-aged and younger subjects (p<0.05). Additionally, in older subjects,
      impaired walking performance was associated with impaired cognitive performance
      in dual task walking. The gait changes observed in dual task walking characterize
      decreased gait stability and indicate that cognitively demanding tasks during
      walking have a destabilizing effect on gait and may place older people at a
      greater risk of falling.

PMID- 16959489
TI  - Hydrocephalus associated with Guillain-Barre syndrome.
AB  - A 68-year-old man developed progressive four-limb weakness and areflexia 17 days
      after an influenza vaccination. He was diagnosed with Guillain-Barre syndrome
      (GBS), and remained ventilator dependent and bed-bound for 3 months, despite
      plasmapheresis and immunoglobulin infusion. However, cognitive impairment,
      excessive daytime sleepiness, and motor disability were still present, even when
      he was no longer ventilator dependent. Brain computerized tomography scan and
      isotope cisternography was consistent with normal pressure hydrocephalus. His
      motor control and cognitive function recovered almost completely after insertion
      of a ventriculoperitoneal shunt. Although hydrocephalus is not frequently
      associated with GBS, our case report indicates that brain imaging is necessary in
      GBS patients whose cognitive functions deteriorates after disease onset.

PMID- 16959490
TI  - Glycosyl bis-porphyrin conjugates: synthesis and potential application in PDT.
AB  - Syntheses of new glycosylated neutral and cationic porphyrin dimers linked at the
      meso-position via a flexible hydrocarbon chain are described. A detailed 1H and
      13C NMR study allows their complete structural elucidation. The UV-visible,
      fluorescence and MALDI mass spectra are also presented. Photocytotoxicities of
      these compounds against K562 leukaemia cell line are compared to those of
      Photofrin II.

PMID- 16959491
TI  - Alternative methods of identifying the oxidation of metallic nanoparticles
      embedded in a matrix.
AB  - We compare methods for valence-state analysis based on energy-loss near-edge
      structure (ELNES), including the white-line ratio (WLR), pre-edge peak (prepeak)
      and post-edge peak (postpeak) techniques. Starting from multiple-scattering
      calculations, we correlate the appearance of a prepeak in the O-K edge and
      postpeak in the L-edge with oxidation of a transition metal (TM). The ability to
      use more than one technique is especially advantageous for a nanocomposite of
      metallic nanoparticles embedded in a matrix, as we show for the case of iron
      nanoparticles in a silica matrix.

PMID- 16959492
TI  - Erythropoietin is neuroprotective against NMDA-receptor-mediated excitotoxic
      brain injury in newborn mice.
AB  - Using an established mouse model of human periventricular leukomalacia, we
      investigated whether EPO could reduce excitotoxic damage. When administered 1 h
      following intracerebral injection of 10 microg ibotenic acid at day 5 of life,
      both a single injection of EPO (5000 IU/kg bw) and repetitive administrations of
      EPO reduced white and gray matter lesion size. The therapeutic window for
      protection was small as the protective effect of EPO was lost when EPO
      administration was delayed to 4 h post-insult. EPO-mediated upregulation of EPO
      R, but not EPO, mRNA was observed within 4 h of the excitotoxic insult. The EPO
      effect was gender independent. Minor hematopoetic effects were observed following
      EPO treatment. We conclude that a single dose of EPO is sufficient to reduce
      excitotoxic brain injury and may therefore possess therapeutic relevance in the
      clinical setting.

PMID- 16959493
TI  - Partial mitochondrial complex I inhibition induces oxidative damage and perturbs
      glutamate transport in primary retinal cultures. Relevance to Leber Hereditary
      Optic Neuropathy (LHON).
AB  - Leber Hereditary Optic Neuropathy (LHON) is a maternally inherited form of visual
      loss, due to selective degeneration of retinal ganglion cells. Despite the
      established aetiological association between LHON and mitochondrial DNA mutations
      affecting complex I of the electron transport chain, the pathophysiology of this
      disorder remains obscure. Primary rat retinal cultures were exposed to increasing
      concentrations of rotenone to titrate complex I inhibition. Neural cells were
      more sensitive than Muller glial cells to rotenone toxicity. Rotenone induced an
      increase in mitochondrial-derived free radicals and lipid peroxidation. Sodium
      dependent glutamate uptake, which is mostly mediated by the glutamate transporter
      GLAST expressed by Muller glial cells, was reduced dose-dependently by rotenone
      with no changes in GLAST expression. Our findings suggest that complex I-derived
      free radicals and disruption of glutamate transport might represent key elements
      for explaining the selective retinal ganglion cell death in LHON.

PMID- 16959494
TI  - Cloning and expression of an outer membrane protein ompTS of Aeromonas hydrophila
      and study of immunogenicity in fish.
AB  - The outer membrane proteins of the warm water fish pathogen, Aeromonas hydrophila
      have a role in the virulence of the organism and are potential candidates for
      vaccine development. In this study, the gene encoding an outer membrane protein
      designated ompTS was amplified by PCR excluding the region coding for signal
      peptide, cloned in pQE 30-UA Vector and expressed using induction with isopropyl
      thiogalactoside (IPTG). The size of the expressed protein was 37 kDa as estimated
      by migration in 10% sodium dodecyl sulphate-polyacrylamide gel electrophoresis
      (SDS-PAGE). Polyclonal antibodies were raised in mice and rabbit against the
      purified protein and the reaction of the antibody was confirmed by Western
      blotting using the purified protein and A. hydrophila cultures. The Indian major
      carp, Labeo rohita Hamilton was immunized using the purified protein and
      developed antibodies with mean titers of 1:4000 on day 14 and 1:12,000 on day 28
      showing promise that the protein is highly immunogenic in fish.

PMID- 16959495
TI  - Optimal EPI parameters for reduction of susceptibility-induced BOLD sensitivity
      losses: a whole-brain analysis at 3 T and 1.5 T.
AB  - Most functional magnetic resonance imaging (fMRI) studies record the blood oxygen
      level-dependent (BOLD) signal using fast gradient-echo echo-planar imaging (GE
      EPI). However, GE EPI can suffer from substantial signal dropout caused by
      inhomogeneities in the static magnetic field. These field inhomogeneities occur
      near air/tissue interfaces, because they are generated by variations in magnetic
      susceptibilities. Thus, fMRI studies are often limited by a reduced BOLD
      sensitivity (BS) in inferior brain regions. Recently, a method has been developed
      which allows for optimizing the BS in dropout regions by specifically adjusting
      the slice tilt, the direction of the phase-encoding (PE), and the z-shim moment.
      However, optimal imaging parameters were only reported for the orbitofrontal
      cortex (OFC) and inferior temporal lobes. The present study determines the
      optimal slice tilt, PE direction, and z-shim moment at 3 T and 1.5 T, otherwise
      using standard fMRI acquisition parameters. Results are reported for all brain
      regions, yielding a whole-brain atlas of optimal parameters. At both field
      strengths, optimal parameters increase the BS by more than 60% in many voxels in
      the OFC and by at least 30% in the other dropout regions. BS gains are shown to
      be more widespread at 3 T, suggesting an increased benefit from the dropout
      compensation at higher fields. Even the mean BS of a large brain region, e.g.,
      encompassing the medial OFC, can be increased by more than 15%. The maps of
      optimal parameters allow for assessing the feasibility and improving fMRI of
      brain regions affected by susceptibility-induced BS losses.

PMID- 16959496
TI  - Stimulation of subthalamic nucleus inhibits emotional activation of fusiform
      gyrus.
AB  - In patients with Parkinson's disease, deep brain stimulation of the subthalamic
      nucleus is known to impair their ability to correctly identify facial expressions
      of negative emotions. This difficulty exists only when the stimulator is active.
      The reason for the impairment is unknown. To test the hypothesis that the
      stimulation itself is responsible, we used positron emission tomography to
      compare functional activations of brain regions in nine patients with Parkinson's
      disease treated with surgically implanted electrodes into both subthalamic
      nuclei, and 22 healthy volunteers. Both groups viewed images with neutral or
      emotional content from Aarhus University's standard Empathy Picture System ()
      with 360 images of people in pleasant, unpleasant or neutral real-life
      situations, presenting either the situations or close-ups of the facial
      expressions of the people involved. Both groups, the patients with stimulation
      OFF and the healthy volunteers, had raised regional blood flow rates (rCBF) in
      the right fusiform gyrus when they viewed emotionally expressive faces compared
      to neutral faces. With stimulation turned on, this response was significantly
      inhibited in the patients because of a raised rCBF at baseline during the neutral
      faces. Stimulation of the STN did not alter fusiform reaction to emotionally
      pregnant scenes; nor did healthy volunteers and patients react differently to
      these stimuli regardless of stimulation status. Also, STN stimulation raised the
      emotional activation of the anterior cingulate and lowered the activity of the
      putamen. The findings suggest that the stimulation of the subthalamic nucleus
      interferes with the integration of specific neocortical networks involved in the
      recognition of facial expressions.

PMID- 16959498
TI  - Exploring the false discovery rate in multichannel NIRS.
AB  - Near infrared spectroscopy (NIRS), an emerging non-invasive tool for functional
      neuroimaging, has evolved as a multichannel technique allowing simultaneous
      measurements through many channels ranging from below ten to above hundred.
      Simultaneous testing of such a large number of channels escalates the risk of
      Type I error, therefore multiplicity correction is unavoidable. To date, only a
      few studies have considered this issue using Bonferroni correction, which is an
      effective conservative solution, but may be too severe for neuroimaging. Its
      power varies in inverse proportion of the number of channels, which varies among
      NIRS studies depending on selected region of interest (ROI), thereby leading to a
      subjective inference. This problem may be well circumvented by a more
      contemporary approach, called false discovery rate (FDR) that is widely being
      adopted in functional neuroimaging. An FDR-based procedure controls the expected
      proportion of erroneously rejected hypotheses among the rejected hypotheses,
      which offers a more objective, powerful, and consistent measure of Type I error
      than Bonferroni correction and maintains a better balance between power and
      specificity. In this technical note, we examine FDR approach using examples from
      simulated and real NIRS data. The FDR-based procedure could yield 52% more power
      than Bonferroni correction in a 172-channel real NIRS study and proved to be more
      robust against the changing number of channels.

PMID- 16959497
TI  - Young adult stimulant users' increased striatal activation during uncertainty is
      related to impulsivity.
AB  - BACKGROUND: Young adults who use stimulants (e.g., cocaine, amphetamines) are at
      particular risk of transitioning to dependence. Previously, we demonstrated
      increased risk-taking in young adults who had used stimulants (Leland, D.S.,
      Paulus, M.P., 2005. Increased risk-taking decision-making but not altered
      response to punishment in stimulant-using young adults. Drug. Alcohol Depend. 78,
      83-90). Since outcome uncertainty is a critical element of risk, we investigated
      whether such individuals have different neural responses to uncertainty than
      their stimulant-naive peers. METHOD: Eleven young adults (age 18-25) who had used
      stimulants were compared with 11 age- and education-matched stimulant-naive
      controls using functional magnetic resonance imaging and a card prediction task
      with relatively certain/uncertain outcome conditions. RESULTS: The caudate, an
      area involved in processing salient events, was among those regions more active
      in users than controls in response to uncertainty. Personality measures revealed
      that users were more impulsive than controls, and that neural response to
      uncertainty in a number of areas, including the thalamus/caudate, was positively
      correlated with impulsivity. CONCLUSIONS: These results are consistent with the
      idea that young adults who have used stimulants find uncertainty particularly
      salient, due in part to preexisting differences in impulsivity, and may be
      subject to more "action pressure" when making decisions under uncertainty. This
      neural and personality profile may constitute a marker for increased risk of
      stimulant use.

PMID- 16959499
TI  - In vivo SPECT imaging of muscarinic acetylcholine receptors using (R,R) 123I-QNB
      in dementia with Lewy bodies and Parkinson's disease dementia.
AB  - INTRODUCTION: Alterations in cholinergic function have been reported to be
      associated with dementia. The aim of this study was to investigate differences in
      the distribution of muscarinic acetylcholine receptors (mAChRs) using (R,R) 123I
      iodo-quinuclidinyl-benzilate (QNB) and single photon emission computed tomography
      (SPECT) in dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD)
      and age-matched controls. 123I-QNB binding was also compared to the corresponding
      cerebral perfusion changes in the same subjects. METHODS: 63 subjects (24
      controls, 14 DLB, 25 PDD) underwent 123I-QNB and perfusion 99mTc-exametazine
      SPECT scanning. Image analysis, using statistical parametric mapping (SPM99),
      involved spatial normalisation of each image to a customised template, followed
      by smoothing and intensity normalisation of each image to its corresponding mean
      whole brain uptake. Group effects and correlations were assessed using two sample
      t tests and linear regression respectively. RESULTS: Relative to controls,
      significant elevation of 123I-QNB binding was apparent in the right occipital
      lobe in DLB and right and left occipital lobes in PDD (height threshold
      p<or=0.001 uncorrected). PDD also showed significant loss in uptake in frontal
      regions and temporal lobes bilaterally that was not present in DLB. These
      patterns appeared to be independent of any corresponding rCBF changes.
      CONCLUSION: Significant elevation of mAChRs in the occipital lobe was associated
      with DLB and PDD. This may relate to the visual disturbances that are prevalent
      in these disorders. Further studies are required in order to establish the role
      of mAChRs in visual function.

PMID- 16959500
TI  - Plasticity in the adult language system: a longitudinal electrophysiological
      study on second language learning.
AB  - Event-related potentials (ERPs) were used to trace changes in brain activity
      related to progress in second language learning. Twelve English-speaking exchange
      students learning German in Switzerland were recruited. ERPs to visually
      presented single words from the subjects' native language (English), second
      language (German) and an unknown language (Romansh) were measured before (day 1)
      and after (day 2) 5 months of intense German language learning. When comparing
      ERPs to German words from day 1 and day 2, we found topographic differences
      between 396 and 540 ms. These differences could be interpreted as a latency shift
      indicating faster processing of German words on day 2. Source analysis indicated
      that the topographic differences were accounted for by shorter activation of left
      inferior frontal gyrus (IFG) on day 2. In ERPs to English words, we found Global
      Field Power differences between 472 and 644 ms. This may due to memory traces
      related to English words being less easily activated on day 2. Alternatively, it
      might reflect the fact that--with German words becoming familiar on day 2-
      English words loose their oddball character and thus produce a weaker P300-like
      effect on day 2. In ERPs to Romansh words, no differences were observed. Our
      results reflect plasticity in the neuronal networks underlying second language
      acquisition. They indicate that with a higher level of second language
      proficiency, second language word processing is faster and requires shorter
      frontal activation. Thus, our results suggest that the reduced IFG activation
      found in previous fMRI studies might not reflect a generally lower activation but
      rather a shorter duration of activity.

PMID- 16959501
TI  - Posture influences motor imagery: an fMRI study.
AB  - Motor imagery is widely used to study cognitive aspects of the neural control of
      action. However, what is exactly simulated during motor imagery is still a matter
      of debate. On the one hand, it is conceivable that motor imagery is an embodied
      cognitive process, involving a simulation of movements of one's own body. The
      alternative possibility is that, although motor imagery relies on knowledge of
      the motor processes, it does not entail an actual motor simulation that is
      influenced by the physical configuration of one's own body. Here we discriminate
      between these two hypotheses, in the context of an established motor imagery
      task: laterality judgments of rotated hand drawings. We found that reaction times
      of hand laterality judgments followed the biomechanical constraints of left or
      right hand movements. Crucially, the position of subjects' own left and right arm
      influenced laterality judgments of left and right hands. In neural terms, hand
      laterality judgments activated a parieto-frontal network. The activity within
      this network increased with increasing biomechanical complexity of the imagined
      hand movements, even when the amount of stimulus rotation was identical.
      Moreover, activity in the intraparietal sulcus was modulated by subjects' own
      hand position: a larger incongruence in orientation between the subjects' hand
      and the stimulus hand led to a selective increase in intraparietal activity. Our
      results indicate that motor imagery generates motor plans that depend on the
      current configuration of the limbs. This motor plan is calculated by a parieto
      frontal network. Within this network, the posterior parietal cortex appears to
      incorporate proprioceptive information related to the current position of the
      body into the motor plan.

PMID- 16959502
TI  - Likelihood-ratio tests for positive selection of human and mouse duplicate genes
      reveal nonconservative and anomalous properties of widely used methods.
AB  - Two commonly used methods based on likelihood-ratio tests (LRTs) for detecting
      positive Darwinian selection at the molecular level were applied to a data set of
      604 gene families containing two members in the human genome and two members in
      the mouse genome. These methods detected positive selection in a very high
      proportion of families; in over 50% of families, there was significant evidence
      of positive selection by one or both methods. However, less than a third of
      families showing evidence for positive selection by at least one of the methods
      showed evidence of positive selection by both methods. The outcome of these tests
      was predicted better by sequence length, G+C content at third-codon positions,
      and the level of synonymous substitution than by the level of nonsynonymous
      substitution or the ratio of nonsynonymous to synonymous substitution. These
      results suggested that LRT-based tests for positive selection may be sensitive to
      certain factors that make it difficult to reconstruct the true pattern of
      nucleotide substitution.

PMID- 16959503
TI  - RNAi-mediated inhibition of the glucosylceramide synthase (GCS) gene: A
      preliminary study towards a therapeutic strategy for Gaucher disease and other
      glycosphingolipid storage diseases.
AB  - Small interference RNAs (siRNAs) have recently been used in various experimental
      settings to silence gene expression. In some of them, chemically synthesized or
      in vitro transcribed siRNAs have been transfected into cells. In others, siRNAs
      have been expressed endogenously from siRNA expression vectors. Enzyme
      replacement and substrate deprivation therapies are currently used to treat
      Gaucher disease. Although good results have been reported, there are several
      limitations and side effects that make necessary to search for new alternatives.
      We present a new approach based on the inhibition of the GCS gene using siRNAs as
      a potential therapeutic strategy for Gaucher disease. We have designed four
      siRNAs for the human GCS gene and transfected them into HeLa cells. A clear
      reduction of GCS RNA levels and enzyme activity was obtained using two of the
      four siRNAs. Furthermore, a reduction in glucosylceramide synthesis was also
      observed. Similar results were obtained when plasmids expressing shRNAs
      (targeting the same sequences) were transfected into the cells. The inhibition of
      the mouse homolog Ugcg gene was also achieved, using a siRNA that targeted both
      human and mouse sequences.

PMID- 16959504
TI  - Diagnosis of paratuberculosis in a dairy herd native to Brazil.
AB  - Paratuberculosis (PTB) in Brazil has previously only been reported in imported
      animals and is officially considered as an exotic disease. A dairy herd, which
      had no imported animals, presented clinically suspect animals and was
      investigated for paratuberculosis using faecal culture, histopathology, indirect
      ELISA and the agar gel immunodiffusion test. Infection with Mycobacterium avium
      subsp. paratuberculosis (Map) was confirmed by culture of faeces from five cows
      with clinical symptoms of PTB and in 7/24 randomly selected asymptomatic cows
      from the same herd. Two cows with clinical symptoms were necropsied and their
      tissues were positive for Map by culture and histopathology. Twelve asymptomatic,
      randomly selected cows were positive on ELISA. The results confirmed the presence
      of PTB in this dairy herd and for the first time demonstrated the disease in a
      herd of native-bred cattle in Brazil.

PMID- 16959505
TI  - Research and practice in the United Kingdom: the place of the veterinarian.

PMID- 16959506
TI  - Detection of thermotolerant Campylobacter in ostriches (Struthio camelus) in
      Italy.
AB  - During the period January 2004 to December 2005 four different ostrich farms were
      investigated to evaluate the presence of thermotolerant Campylobacter. A total of
      150 ostriches were examined and all were found to be clinically healthy.
      Campylobacter spp. were isolated from 60/150 cloacal swabs. Among the isolates,
      48 were identified as Campylobacter jejuni whereas the remainder were identified
      as Campylobacter coli. Campylobacter lari was not isolated. The ostriches,
      although apparently in a healthy body condition, can be considered,
      theoretically, as potential Campylobacter carriers.

PMID- 16959507
TI  - Genetic disorders and the quest for candidate genes: hypotheses worth testing.

PMID- 16959508
TI  - A thousand racehorse trainers cannot be wrong - can they?

PMID- 16959509
TI  - A benign congenital myopathy in an inbred Samaritan family.
AB  - We describe a novel form of myopathy in a mother and her two daughters from an
      inbred Samaritan family. The patients displayed severe neonatal hypotonia,
      lethargy and dysmorphic features. Motor milestones were delayed; however, the
      hypotonia and muscle weakness gradually improved during the first 2 years of life
      and independent walking was achieved by 18 months. The mother at the age of 23
      years shows myopathic facies and minimal proximal weakness. Her intelligence is
      normal. Her muscle biopsy revealed central nuclei and disruption of the
      intermyofibrillary network with moth eaten and spiral fibers. Mutations in SMN,
      MTM1 and the myotonic dystrophy genes were excluded. We suggest this is a new
      benign form of congenital myopathy. Inheritance is probably autosomal recessive.

PMID- 16959510
TI  - Contributions of 3'-overhang to the dissociation of small interfering RNAs from
      the PAZ domain: molecular dynamics simulation study.
AB  - RNA interference (RNAi) is a 'knock-down' reaction to reduce expression of a
      specific gene through highly regulated, enzyme-mediated processes. Small
      interfering RNAs (siRNAs) are RNA molecules that play an effector role in RNAi
      and can bind the PAZ domains present in Dicer and RISC. We investigated the
      interaction between the PAZ domain and the siRNA-like duplexes through
      dissociation molecular dynamics (DMD) simulations. Specifically, we focused on
      the response of the PAZ domain to various 3'-overhang structures of the siRNA
      like duplexes. We found that the siRNA-like duplex with the 3' UU-overhang made
      relatively more stable complex with the PAZ domain compared to those with 3' CC-,
      AA-, and GG-overhangs. The siRNA-like duplex with UU-overhang was easily
      dissociated from the PAZ domain once the structural stability of the complex is
      impaired. Interestingly, the 3' UU-overhang spent the least time at the periphery
      region of the binding pocket during the dissociation process, which can be mainly
      attributable to UU-overhang's smallest number of hydrogen bonds.

PMID- 16959511
TI  - Computation of through-space NMR shielding effects by aromatic ring-cation
      complexes: substantial synergistic effect of complexation.
AB  - The HF-GIAO method in Gaussian 03 was employed to calculate the NMR isotropic
      shielding values of a diatomic hydrogen probe and to predict the through-space
      proton NMR shielding increment surfaces above benzene complexed with ammonium,
      lithium, sodium, potassium, magnesium or calcium ion. The sum of the calculated
      isotropic shielding values for the proximal hydrogen of a diatomic hydrogen probe
      over benzene and those calculated at appropriate positions relative to cations
      were subtracted from the isotropic shielding values calculated for the complexes.
      The result is a shielding increment for complexation. Complexation results in a
      synergistic effect on NMR shielding. Enhanced shielding was observed over the pi
      electron cloud of benzene upon complexation with the cations, more than the sum
      of the separate effects of the aromatic ring and the charge. The results are
      interpreted in terms of polarization of the pi cloud of benzene by the cation and
      its consequences.

PMID- 16959512
TI  - Phenotypic plasticity in response to low quality diet in the South American
      omnivorous rodent Akodon azarae (Rodentia: Sigmodontinae).
AB  - We studied the responses in the omnivorous rodent A. azarae submitted to a low
      quality diet at morphological, physiological and biochemical levels. At short
      term, a decrease in body mass occurred. A later increase in food consumption
      constituted a strategy that allowed a temporal recovery of physical condition.
      However, hyperphagia appeared not to be enough to maintain physical condition
      after 30 days of low quality diet consumption. At the morphological level, an
      increase in length (9%) of the anterior portion of the gut occurred, the part of
      the gut where digestion and absorption take place. A decrease in small intestine
      weight could be related with the long-term impairment of body condition.
      Inhibition of sucrase specific activity in small intestine would indicate a down
      regulation of sucrase-isomaltase complex. Total maltase specific activity in
      small intestine was not affected suggesting an up-regulation of sucrase
      independent maltase specific activity. A down-regulation of protease specific
      activity in small intestine occurred in response to low quality diet. The
      specific activity of disaccharidases in caecum and large intestine was down
      regulated. The strategies and constraints at different levels of A. azarae upon
      low quality diet are discussed.

PMID- 16959513
TI  - Stomach lysozymes of the three-toed sloth (Bradypus variegatus), an arboreal
      folivore from the Neotropics.
AB  - Lysozymes are antimicrobial defences that act as digestive enzymes when expressed
      in the stomach of herbivores with pre-gastric fermentation. We studied this
      enzyme in the complex stomach of the three-toed sloth (Bradypus variegatus), a
      folivore with pre-gastric fermentation. Lysozymes were identified by SDS-PAGE and
      immunoblotting in all portions: diverticulum, pouch, glandular and muscular
      prepyloric area with 14.3 kDa of molecular mass. Purified lysozymes from all
      areas but the diverticulum were characterized by MALDI-TOF, optimal pH, optimal
      ionic strength, and specific activity. The differences observed suggested at
      least three isoforms. The optimal pHs were similar to the pH of the stomach
      portion where the enzymes were isolated. The lysozyme from the pouch
      (fermentation chamber) exhibited higher specific activity and concentration than
      the others. The specific activity of the enzyme from the acid muscular prepyloric
      portion was comparable to that reported in the cow abomasums; however, its
      concentration was lower than that observed in cow. This distinctive pattern of
      secretion/specific activity and overall low concentration suggests different
      roles for the lysozymes in this herbivore compared to Artiodactyla. We postulate
      that sloth stomach lysozymes may still be antimicrobial defences by protecting
      the microbial flora of the fermentation chamber against foreign bacteria.

PMID- 16959514
TI  - Seasonal changes in physiological responses and evaluation of "well-being" in the
      Venus clam Chamelea gallina from the Northern Adriatic Sea.
AB  - Chamelea gallina is an infaunal bivalve, widespread in sandy bottoms along
      Mediterranean coasts. It is an important economic resource for fisheries in the
      Adriatic, although in recent years over-fishing, and other concurrent factors,
      have dramatically decreased clam harvesting. In this context, it is of great
      interest to gain information on seasonal variations in the physiological
      performance of clams, for an overall evaluation of their well-being. In this
      study, laboratory experiments were performed to define allometric relationships
      and effects of temperature on clearance and respiration rates of C. gallina. The
      mean values of b coefficients were calculated and used to correlate physiological
      measurements to 'standard' body mass, when seasonally collected clams were
      analysed. The highest clearance rate (0.42 L h(-1)) was measured in clams
      collected in July 2000; the highest respiration rate (12.22 micromol O2 h(-1))
      was observed in July 2001, leading to a negative scope for growth (-2.8 J h(-1)).
      The influence of environmental and endogenous factors, mostly reproduction, was
      discussed. Survival in air and condition indices, showing higher stress
      conditions in December 2000 and July 2001, were in good agreement with the other
      physiological measurements. The physiological responses examined in this study
      appear to be suitable for providing detailed indications on the well-being of C.
      gallina and may be useful for future studies aimed at eco-sustainable management
      of the resource.

PMID- 16959515
TI  - Characterization and kinetics studies of water buffalo (Bubalus bubalis)
      myoglobin.
AB  - The colour of buffalo (Bubalus bubalis L.) meat is darker than bovine meat. Since
      meat colour depends on the concentration of myoglobin (Mb) and its oxidation
      state, we have determined the main structural and functional properties of
      buffalo Mb. Buffalo Mb was purified from longissimus dorsi muscles and its
      molecular mass determined by ESI Q-TOF mass spectrometry. The molecular mass
      17,034.50 was 86.20 Da higher than the bovine Mb. This was confirmed by analysing
      its primary structure, using a combined approach based on Edman degradation and
      MALDI-TOF mass spectrometry. Comparing the amino acid sequences of both Mbs, we
      found three amino acid differences out of 153 amino acid residues. One is a
      conservative substitution (D(bov)141E(buf)), and the other two (A(bov)19T(buf)
      and A(bov)117D(buf)) are nonconservative. These amino acid substitutions are
      unlikely to cause structural changes because they are located far from the heme
      binding pocket, as revealed by the 3D structure of buffalo Mb elaborated by
      homology modelling. Stability analyses show no difference with the bovine Mb for
      helix E and only minor differences in the stability values for helices A and G.
      Moreover, autoxidation rates of purified buffalo and bovine myoglobins at 37
      degrees C, pH 7.2, were almost identical, 0.052+/-0.001 h(-1) and 0.054+/-0.002
      h(-1), respectively, as were their oxygen-binding Kd values, 3.7+/-0.1 microM and
      3.5+/-0.1 microM, respectively. The percent of MetMb values were almost
      identical. The results presented here suggest that the darker buffalo meat
      depends on factors other than the oxidation rate of its Mb, as, for example, the
      Mb content (0.393+/-0.005 g/100 g of tissue) and consequently MetMb, which are
      almost twice as high as bovine meat (Mb: 0.209+/-0.003 g/100 g of tissue).

PMID- 16959516
TI  - [Giving blood: an individual right or the expression of a social responsibility?
      The donors' position in the debates on blood transfusion].
AB  - This debate questions the donor's position within the transfusional framework.
      How are blood donation regulations initiated and implemented? Experts called upon
      this question insist on the necessity to better inform about such regulations so
      that they can be rapidly approved and in order to keep donors from adverse
      reactions linked to blood donations. How to make donors' rejections more
      tolerable? Contra-indications are a source of anxiety for the person whose blood
      sample is not accepted. While blood transfusion has never been safer in the past
      than it is today in wealthy countries, one should ask the question whether the
      donor is or not the victim of doubts still weighing down on this activity.
      Implementing the precautionary principle may indeed lead transfusion supervisors
      to take brutal decisions detrimental to the donor, seeming rather inspired by
      political or media pressures than calling on scientific or economic rigorous
      principles. What does the donor selection aim at in terms of prevention and
      public health? What about the renewal of donor associations' directors? Where are
      we at with the homosexual rejection trends? Such are the issues as those induced
      by the current debate.

PMID- 16959517
TI  - [Treatment response evaluation by functional imaging].
AB  - Imaging in cancer plays a capital role to guide the clinician in his choice of
      therapies. We will discuss the new techniques available to predict and evaluate
      treatment response in oncology. The method of reference to evaluate treatment
      response is based on the measure of lesion size. Functional imaging doesn't
      evaluate size, but rather a physiological or molecular feature, which is probably
      modified earlier in response to treatment. Dynamic contrast-enhanced functional
      imaging of microcirculation follows the biodistribution of a contrast agent and
      analyses tumour vascularization. Diffusion-weighted Magnetic Resonance Imaging
      differentiates free and restrained water molecules in tissues, reflecting tumor
      cellularity. Nuclear Magnetic Resonance spectroscopy is an application of MRI
      that yields information on the metabolic content of a tissue. It detects relative
      quantities of various molecules which differ in tumour compared to normal tissue.
      Positon-emission tomography using (18)FDG is a nuclear medicine technique which
      gives information on tissue metabolism. Captation of FDG is proportional to the
      proliferative activity and the number of viable cells in a tumour. Human studies
      concerning these techniques are still quite preliminary, and the medical
      community must determine their potential in clinical practice to evaluate
      treatment response in oncology.

PMID- 16959518
TI  - [Image-guided radiotherapy by in-room CT-linear accelerator combination].
AB  - Target localization has become increasingly important in the advent of IMRT, as
      treatment margins are reduced and target doses are increased with high-dose
      gradients outside this target volume. The in-room CT on rails-LINAC system allows
      CT imaging while the patient remains immobilized in the treatment position just
      prior to treatment. The anatomic inter- and intra-fractional variations can be
      therefore quantified during a course of treatment. The position of the tumour can
      be checked and corrected before the fraction. In case of modification of tumour
      shape, a re-planning of the treatment is also feasible. However, several issues
      remain: the integration with routine clinical treatment due to a lack of software
      tools, the frequency of imaging, and the cost-efficiency ratio. The clinical
      experience is yet very limited but CT-image-guided radiotherapy appears promising
      for prostate, brain and spinal tumours.

PMID- 16959519
TI  - [Radiofrequency ablation of lung and bone tumors].
AB  - Radiofrequency ablation was initially used for treatment of liver primary and
      metastatic disease. Recently the technique has been used for treatment of kidney,
      bone, lung, and mammary neoplasms. Radiofrequency electrode is positioned in the
      target tumor under imaging guidance. For lung or bone tumors, computed tomography
      is the only method of guidance. Radiofrequency ablation of lung tumor is
      performed in order to cure the disease and consequently pre-imaging work-up must
      be equivalent t pre-surgical work-up. Today lung radiofrequency ablation is
      mostly performed in patients bearing less than 5 tumors and tumors smaller than 4
      cm. In such a population of patients radiofrequency ablation has demonstrated a
      local efficacy of 92% at 9 months, with 95% and 87% for tumor smaller and larger
      than 2 cm, respectively. Survival benefit still remains unclear. Bone tumors are
      mostly treat for pain palliation. In a population of 45 patients with a minimal
      pain of 4 on a scale from 0 to 10, radiofrequency was able to provide a drop of
      at least 3 points in 84% of patients. Radiofrequency provides a minimally
      invasive cure of small tumors. It can also be used as a palliative tool.

PMID- 16959520
TI  - [The French preliminary experience of the use of a seed-projector for exclusive
      iodine 125 prostate brachytherapy: feasibility and acute toxicity].
AB  - PURPOSE: To analyse a new technique for prostate brachytherapy with permanent
      Iodine implants characterized by the use of a seed projector after a 3D
      dosimetric peroperative treatment planning (FIRST technique). PATIENTS AND
      METHOD: 395 patients have been treated in France with this technique in six
      radiotherapy centres between November 2002 and December 2005 for a localized
      prostate cancer. RESULTS: Thirteen patients (3.3%) developped a urinary
      retention, and respectively 7.8 and 26.5% an acute RTOG grade 3 and 2 toxicity.
      The 6-weeks IPSS score was equal or lower to 15 in 73% with a 11 median IPSS
      value. A failure of the loading with the seed-projector, leading to a manual
      loading of the seeds, occurred in 9 patients (2.3%) in two centres, directly
      related to the loading procedure with the seed-projector in 5 cases. The median
      duration of the procedure was reduced by 30 minutes for the patients treated in
      2005. CONCLUSIONS: This multicenter study establishes the feasibility of the
      routine use of a seed projector for permanent iodine 125 prostate implants with
      an initial tolerance similar to the best results published for other implants
      techniques.

PMID- 16959521
TI  - [History of spermatozoon and changing views].
AB  - With Ham, Leeuwenhoek discovered animalcules in human semen in 1677, without
      theoretical interpretations. Discussions focused on the respective role of ovum
      and animalcules during two centuries with erroneous doctrines. Modern ideas on
      status and origin of animalcules are associated with the development of the cell
      theory. Animalcules became spermatozoa. In 1875, Hertwig observed that the head
      of spermatozoon becomes a pronucleus and combines with the female pronucleus,
      thus establishing the concept that fertilization is the conjugation of two cells.
      During the first half of 20th century, endocrinology and genetics influenced
      management of infertile couples. Cryopreservation, analyses of ultrastructural
      morphology improved knowledges of normal and abnormal male gametes. In Vitro
      Fertilization and more IntraCytoplasmic Sperm Injection opened new views on the
      role of spermatozoa in human generation. Genetics and procreation were more and
      more so linked that each perspective of further advances shocked ethical
      considerations as transgression of natural biology. The future of spermatozoon in
      human reproductive programs remains a mystery according to, for example,
      experimental development using stem cell cultures.

PMID- 16959522
TI  - [To FIV or not to FIV: Will gestational surrogacy be an indication for assisted
      reproductive techniques?].
AB  - Gestational surrogacy covers three different and often mixed up situations. In
      the first case (that of full surrogacy), the surrogate mother carries and has the
      baby anonymously. The child has been conceived by artificial insemination with
      her own oocyte and the help of the financing father, who has legally recognised
      the child before birth. This constitutes surrogacy motherhood practice, which was
      condemned by a judgment of the French Court of Cassation, in 1991. In the second
      case (gestational surrogacy), the mother only carries an embryo conceived in
      vitro by the biological parents to whom she will give back the baby when he is
      born. The filiation tie between the child and his parents is thereby maintained,
      the surrogate mother's role being limited to that of gestation. In the third
      case, the surrogate mother carries an embryo, the result of in vitro
      fertilization of the oocytes of a donor and the father's sperm. From the moment
      that surrogacy is not at variance with any of our fundamental rights, we cannot
      but wish that, with the guarantee of a rigorous frame, it might become a medical
      indication for IVF, in precise circumstances of female infertility.

PMID- 16959523
TI  - [Cryopreservation of human embryos by vitrification].
AB  - Vitrification is a cryopreservation strategy where cells are converted into a
      glass-like amorphous solid which is free of any crystalline structure. Such
      process is achieved by a combination of high concentration of cryoprotectant and
      an extremely high cooling rate. In the last years, survival rates of up to 80%
      after thawing and pregnancy rates of almost 30% could be achieved after transfer
      of vitrified embryos at the zygote, cleavage, morula and blastocyst stages. Also
      deliveries of healthy babies have been reported numerous times. To this day, a
      limited interest in this technique can be noted. The explanation may lye in the
      apprehension of many ART units regarding exposure of embryos to high
      concentrations of cryoprotectants and storage in non sterile conditions. The aim
      of the first part of this article, is to analyse if such fears are justified on
      the basis that vitrification mimics conditions already in use for many years in
      slow-cooling procedures where cells are plunged into liquid nitrogen at around 
      30 degrees C and secondly since storage of embryos are now possible in high
      aseptic conditions. In the second part, results on survival after thawing,
      pregnancy rates and baby take home rates of vitrified embryos will be presented
      and the problems associated with vitrification of blastocysts will be discussed.

PMID- 16959524
TI  - [Oocyte-cumulus dialog].
AB  - The dialog between oocyte and cumulus cells brings a major contribution for
      oocyte meiotic and developmental competence. On the one hand, the oocyte will
      modulate follicle growth through specific gene expression (Figalpha, GDF-9,
      BMP15) as well as its meiosis (GPR3 et PDE3A). Beyond its action on
      proliferation, oocyte will control in part the differentiation of cumulus cells
      with a particular involvement of GDF-9, BMP15 in this late maturation process. On
      the other hand, somatic cells are the main targets of gonadotropins and will
      modulate both oocyte growth and maturation. Gap-junctions between oocyte and
      cumulus cells have a major role in this interaction, since they allow the action
      of some oocyte specific genes (GDF9) but also the control of its own metabolism
      and calcium movements. While ovulation will involve gonadotropins action on
      somatic cells, EGF-like factors recruited at the cumulus level will participate
      in this process. Finally we may suspect that improving the knowledge on oocyte
      cumulus dialog will contribute to better define oocyte competence, while bringing
      some clues for in vitro maturation.

PMID- 16959525
TI  - [Quality control of prenatal ultrasound. A role for biometry].
AB  - Because of an increasing demand for limited health care resources as well as an
      increasing impact of legal aspects in ultrasound practice, it has become
      necessary to ensure that screening procedures are cost-effective and clinically
      effective and to develop systems that could help sonographists in certifying
      their practice. Based on the literature, various approaches for quality control
      are reviewed. Special emphasis is put on the use of fetal biometry and
      statistical tools to develop quality control systems based on both qualitative
      and quantitative approach. Besides their potentials for audit and quality
      control, such tools could also be useful during the process of training.

PMID- 16959526
TI  - [Do hysteroscopic metroplasties really improve really reproductive outcome?].
AB  - The aim of metroplasties is to restore a normal uterine anatomy to improve
      obstetrical outcomes in some uterine malformations. The hysteroscopic septoplasty
      cures the septate uterus. It is an effective procedure in the case of recurrent
      abortion losses. It probably improves the rate of live birth in women without
      obstetrical antecedent. For some authors, it could be considered at the time of
      the diagnosis, because of the simplicity of the gesture and the low complication
      rate. The enlarging hysteroscopic metroplasty has certainly a positive impact on
      the obstetrical outcome in patients presenting a uterine hypotrophy or dysmorphy,
      in particular in women exposed in utero to DES. However, the proofs are poor to
      propose this procedure as first-line treatment, apart from specific cases such as
      old null gravid patient or before inclusion in an Assisted Reproductive
      Techniques (ART) program.

PMID- 16959527
TI  - [Transparency of results in assisted reproductive technology].
AB  - Clear results in ART need to take into account the technical performances of the
      centre but also patients selection, cycles cancelling and embryo transfer
      policies. The risk of a partial transparency is an inappropriate selection of
      patients. From classical criterias like pregnancies per oocytes retrievals or
      embryo transfers we are heading towards more global indicators like live births
      of singletons by initiated cycles rate.

PMID- 16959528
TI  - Structural and functional changes in ultrasonicated bovine serum albumin
      solutions.
AB  - Effects of high-intensity ultrasonication on functional and structural properties
      of aqueous bovine serum albumin (BSA) solutions were investigated. The functional
      properties of BSA were altered by ultrasonication. Surface activity of BSA
      increased. Minimal changes were observed in the global structure of BSA but
      surface charge increased particularly at basic pH values (e.g. pH>9). While
      dynamic light scattering measurements indicated that the particle size increased
      up to 3.4 times after 90 min of sonication, no significant increase in the
      oligomeric state of BSA using blue native PAGE was observed. The amount of free
      sulfhydryl groups in BSA after 90 min of sonication decreased. The increased
      particle size and decreased number of free sylfhydryl groups may be attributed to
      formation of protein aggregates. Surface hydrophobicity increased and circular
      dichroism spectroscopy and FTIR analysis indicated changes in the secondary
      structure of BSA. We hypothesize that mechanical, thermal and chemical effects of
      ultrasonication resulted in structural changes in BSA that altered the functional
      properties of the macromolecule which may be attributed to the formation of an
      ultrasonically induced state that differs from a thermally, mechanically or
      solvent induced state.

PMID- 16959529
TI  - Mulligan's mobilization-with-movement, positional faults and pain relief: current
      concepts from a critical review of literature.
AB  - There are an increasing number of reports espousing the clinically beneficial
      effects of Mulligan's mobilization-with-movement (MWM) treatment techniques. The
      most frequent reported effect is that of an immediate and substantial pain
      reduction accompanied by improved function. Prompted by these dramatic effects
      are questions regarding the mechanism(s) of action that underpins MWM. It appears
      timely that a review of the current literature is performed to synthesize and
      evaluate claims of the effectiveness of MWM and speculation about the proposed
      mechanisms of action. This article provides an overview of the literature
      concerning the clinical efficacy, effects and putative mechanisms of action of
      the MWM approach in the treatment of musculoskeletal conditions. The literature
      regarding the mechanisms of action in both the biomechanical and pain science
      paradigms is covered herein by reviewing all available scientific evidence from
      laboratory-based studies. Limitations of reported studies and directions for
      further research are also considered.

PMID- 16959531
TI  - Application of kDNA as a molecular marker to analyse Leishmania infantum
      diversity in Portugal.
AB  - Around the Mediterranean basin Leishmania infantum is an important parasite
      causing canine leishmaniasis and visceral and cutaneous clinical forms in both
      immunocompetent and immunocompromised humans. Efficient monitoring and evaluation
      of epidemiology with discriminatory molecular markers are required. We
      investigated the genetic diversity of L. infantum in Portugal by polymerase chain
      amplification and restriction fragment length polymorphism analysis of
      kinetoplastid DNA, as molecular marker. We analysed 120 Portuguese isolates of L.
      infantum plus 16 other non-Portuguese isolates (as a reference group) from
      humans, dogs and sand flies. The Portuguese population showed a high degree of
      polymorphism with a total of 13 profiles identified. The predominant profile was
      A, which was only detected in the Portuguese samples. The kinetoplastid DNA PCR
      RFLP assay described here was suitable for use directly with biological samples
      and the profiles obtained were stable during long-term growth in vitro and in
      laboratory animals.

PMID- 16959532
TI  - Determination of trace selenium by solid substrate-room temperature
      phosphorescence enhancing method based on potassium chlorate oxidizing phenyl
      hydrazine-1,2-dihydroxynaphthalene-3,6-disulfonic acid system.
AB  - A new method for the determination of trace selenium based on solid substrate
      room temperature phosphorimetry (SS-RTP) has been established. This method was
      based on the fact that in HCl-KCl buffer solution, potassium chlorate could
      oxidize phenyl hydrazine to form chloridize diazo-ion after being heated at 100
      degrees C for 20 min, and then the diazo-ion reacted with 1,2
      dihydroxynaphthalene-3,6-disulfonic acid to form red azo-compound which could
      emit strong room temperature phosphorescence (RTP) signal on filter paper.
      Selenium could catalyze potassium chlorate oxidizing the reaction between phenyl
      hydrazine and 1,2-dihydroxynaphthalene-3,6-disulfonic acid, which caused the
      sharp enhancement of SS-RTP. Under the optimum condition, the relationship
      between the phosphorescence emission intensity (DeltaIp) and the content of
      selenium obeyed Beer's law when the concentration of selenium is within the range
      of 1.60-320 fg spot-1 (or 0.0040-0.80 ng ml-1 with a sample volume of 0.4
      microl). The regression equation of working curve can be expressed as
      DeltaIp=13.12+0.4839CSe(IV) (fg spot-1) (n=6), with correlation coefficient
      r=0.9991 and a detection limit of 0.28 fg spot-1 (corresponding to a
      concentration range of 7.0x10(-13) g ml-1 Se(IV), n=11). After 11-fold
      measurement, R.S.D. were 2.8 and 3.5% for the samples containing 0.0040 and 0.80
      ng ml-1 of Se(IV), respectively. This accurate and sensitive method with good
      repeatability has been successfully applied to the determination of trace
      selenium in Chinese wolfberry and egg yolk with satisfactory results. The
      mechanism of the enhancement of phosphorescence was also discussed.

PMID- 16959533
TI  - The effect of anionic and cationic surfactants on indicators and measurement of
      dissociation constants with two different methods.
AB  - The effects of cationic cetyltrimethylammonium bromide (CTAB), hexadecylpyridinum
      chloride (HDPC) and anionic sodium dodecylsulphate (SDS) surfactants on
      dissociation constants and transition intervals of methyl red, methyl orange and
      cresol red were studied spectrophotometrically. The results show that all studied
      indicators strongly interacted with cationic micelles (CTAB and HDPC). In the
      case of methyl red, relatively strong interaction with anionic surfactant (SDS)
      was obtained. However, no effect of SDS on dissociation constants of cresol red
      and methyl orange was observed. The dissociation constants of indicators were
      calculated with both the proposed and known chemometric (DATAN) method with a
      reasonable agreement on the data achieved.

PMID- 16959534
TI  - Ab initio tools for the accurate prediction of the visible spectra of
      anthraquinones.
AB  - The UV/vis absorption spectra of 101 anthraquinones solvated in two protic
      solvents (methanol and ethanol) has been theoretically predicted using the time
      dependent density functional theory (TD-DFT) for the excited state calculations
      and the polarizable continuum model (PCM) for evaluating bulk solvent effects.
      Two functionals (B3LYP and PBE0) have been used and they provide similar mean
      absolute deviations (approximately 0.09 eV) but mean signed errors presenting
      opposite signs. The errors can be minimized by using simple or multiple linear
      regression, the latter combining the results of both functionals to reach an
      optimal estimation of the lambda(max) (mean absolute error 0.06 eV). Specific
      fittings for the two media have been performed and it turned out that our
      approach is even more efficient for anthraquinones solvated in ethanol.

PMID- 16959535
TI  - Simultaneous determination of cobalt and palladium in micellar media using H
      point standard addition method and partial least square regression.
AB  - A simple, sensitive and selective spectrophotometric method for the simultaneous
      determination of Co(II) and Pd(II) using partial least square (PLS) calibration
      and H-point standard addition method is described. The method is based on the
      complex formation of Co(II) and Pd(II) with 4-(2-pyridylazo) resorcinol (PAR) in
      acidic media and in the presence of sodium dodecyl sulfate (SDS) as a micellizing
      agent. Acidic media and the presence of a micellar system improve selectivity and
      sensitivity, respectively. By applying PLS calibration, Co(II) and Pd(II) can be
      determined in the range of 0.20-2.0 and 0.40-4.0 microg ml(-1), respectively. The
      relative errors of prediction for the determination of Co(II) and Pd(II) in the
      10 prediction samples were 1.69 and 1.72%, respectively. The results of applying
      H-point standard addition method show that Co(II) and Pd(II) can be determined
      simultaneously with concentration ratio of Co(II) to Pd(II) varying between 7:1
      and 1:8 in the mixed samples. Both proposed methods (PLS and HPSAM) were applied
      to the determination of Co(II) and Pd(II) in several alloy solutions with
      satisfactory results.

PMID- 16959536
TI  - Study of the sensitization of tetradecyl benzyl dimethyl ammonium chloride for
      the color development reaction between lysine and sodium 1,2-naphthoquinone-4
      sulfonate and the determination of lysine in pharmaceutical and biological
      samples.
AB  - A rapid, simple and sensitive method for the determination of lysine (Lys) using
      sodium 1,2-naphthoquinone-4-sulfonate (NQS) and tetradecyl benzyl dimethyl
      ammonium chloride (Zeph) is presented in this paper. The method is based on the
      russety product formed from Lys, NQS and Zeph in a buffer solution of pH 9.60,
      and the stoichiometric ratio of the product is 1:2:2. Beer's law is obeyed in a
      range of 0.09-18 microg ml(-1) of Lys at the maximum absorption of 474 nm
      (epsilon(474) is 8.1 x 10(5)l mol(-1)cm(-1)). The equation of linear regression
      is A=0.40427+0.06112C, with a linearly correlation coefficient of 0.9972. The
      limit of detection is 0.07 microg ml(-1), R.S.D. 0.8%, and average recovery rate
      in a range of 98.9-100.1%. This paper further optimizes the determination of Lys
      compared with the previous methods, and the reaction mechanism is studied
      intensively. The proposed method has been successfully applied to the
      determination of Lys in pharmaceutical and biological samples. The common
      components as nutritional additives in pharmaceuticals and other compounds in
      biological samples nearly do not interfere with the proposed method.

PMID- 16959537
TI  - Incident reporting schemes and the need for a good story.
AB  - Incident reporting is a central strategy for improving safety in the NHS (UK
      National Health Service). In this paper we discuss incident reporting in
      anaesthesia. We discuss four schemes for reporting: longstanding, departmental
      based schemes; newer, hospital wide schemes; a national scheme; and an inter
      departmental scheme (developed by the authors). We also discuss an example
      report. We argue that this example report gives an expert 'story' of an incident,
      describing the incident in a way that is useful for the practical activities of
      maintaining and improving safety. We argue that stories are told and retold in
      reporting schemes. The reporting schemes are not just there to collect data but
      to afford the stories of what went wrong. In turn these schemes must be afforded
      stories by the anaesthetists, safety managers and the organisation at large. We
      consider how schemes can be designed to afford a 'good' story, one that is useful
      for the maintaining and improvement of safety.

PMID- 16959538
TI  - Virological effects and safety of combined double filtration plasmapheresis
      (DFPP) and interferon therapy in patients with chronic hepatitis C: A preliminary
      study.
AB  - PURPOSE: In patients with chronic genotype 1b hepatitis C and a high viral load,
      the viral load was reduced by double filtration plasmapheresis (DFPP), followed
      by combined interferon and ribavirin therapy. The safety and virological effects
      of this treatment method were preliminarily investigated. METHODS: In nine
      patients with chronic hepatitis C, DFPP was performed three times on days 1, 2,
      and 4, and the administration of interferon and ribavirin was initiated
      immediately after DFPP on day 1. RESULT: The HCV RNA was undetectable in all
      patients after the plasma was passed through a plasma fractionator (second
      filter) in the DFPP circuit. After 2 weeks, the HCV RNA tended to decrease in the
      DFPP group more than in the control group (-2.45+/-1.12 versus -1.57+/-0.95,
      P=0.073). However, this decrease was not attributable to a sustained virological
      response (SVR) (22.2% versus 18.2%, P=0.822). Most of the adverse events were
      caused by the interferon and ribavirin combination therapy. CONCLUSION: DFPP can
      be safely performed concomitantly with interferon and ribavirin combination
      therapy in chronic hepatitis C patients. The combination may contribute to an
      early virological response. The effect of DFPP on the SVR and its significance
      remain to be clarified.

PMID- 16959539
TI  - Validation of a 24-h physical activity recall in indigenous and non-indigenous
      Australian adolescents.
AB  - The purpose of this study was to evaluate the concurrent validity of a modified
      version of the widely used previous day physical activity recall (PDPAR-24) self
      report instrument in a diverse sample of Australian adolescents comprising
      Aboriginal and Torres Strait Islanders (A&TSI) and non-indigenous high school
      students. A sample of 63 A&TSI and 59 non-indigenous high school students (N=122)
      from five public secondary schools participated in the study. Participants
      completed the PDPAR-24 after wearing a sealed electronic pedometer on the
      previous day. Significant positive correlations were observed between the self
      reported physical activity variables (mean MET level, blocks of vigorous
      activity, and blocks of moderate-to-vigorous physical activity) and 24-h step
      counts. Validity coefficients (rho) ranged from 0.29 to 0.34 (p<0.05). A
      significant inverse correlation was observed for self-reported screen time and 24
      h step count (rho=-0.19, p<0.05). Correlations for A&TSI students were equal to
      or greater than those observed for non-indigenous students. The PDPAR-24
      instrument is a quick, unobtrusive, and cost-effective assessment tool that would
      be useful for evaluating physical activity and sedentary behaviour in population
      based studies.

PMID- 16959540
TI  - Rapid flow cytometric measurement of cytokine-induced phosphorylation pathways
      [CIPP] in human peripheral blood leukocytes.
AB  - Current strategies designed to assess cells in the peripheral blood are limited
      to evaluation of phenotype or delayed measurement [>6 h] of function, usually
      quantifying cytokine production, cytolytic activity, or response to antigens. We
      reasoned that measurable abnormalities in signaling pathways could reflect
      pathological environs that cells experience in the setting of inflammatory
      states/cancer and could be represented in the peripheral blood. Two major
      pathways regulating the immune response are the JAK/STAT and MAPK/ERK pathways.
      These pathways are initiated by ligand-receptor binding and are rapidly
      propagated by subsequent protein phosphorylation cascades. We evaluated the brief
      application of cytokines in vitro to interrogate the early phosphorylation events
      of these signaling pathways in normal peripheral blood mononuclear cells (PBMC).
      Individual cytokine doses and time intervals of treatment were assessed to
      identify conditions useful in a clinical laboratory and as an initial goal to
      induce maximal phosphorylation. Surprisingly, all of the STAT proteins assessed
      and ERK1/2 are maximally phosphorylated within 15 min in human PBMC simply
      following addition of cytokines without preactivation of the cells. At 2 h, cells
      typically return to their basal phosphorylation states. For most of the cytokines
      tested, increased phosphorylation directly correlated with increased
      concentrations of the individual cytokines. These strategies will enable robust
      development of simple blood analyses to identify normal levels as well as
      impairments in STAT and MAPK/ERK signaling pathways associated with various human
      disease states including acute and chronic inflammatory conditions throughout
      clinical immunology.

PMID- 16959541
TI  - Silencing of HIV-1 with RNA interference: a multiple shRNA approach.
AB  - Double-stranded RNA can induce gene silencing via a process known as RNA
      interference (RNAi). Previously, we have shown that stable expression of a single
      shRNA targeting the HIV-1 Nef gene strongly inhibits HIV-1 replication. However,
      this was not sufficient to maintain inhibition. One of the hallmarks of RNAi, its
      sequence specificity, presented a way out for the virus, as single nucleotide
      substitutions in the target region abolished inhibition. For the development of a
      durable gene therapy that prevents viral escape, we proposed to combine multiple
      shRNAs against conserved HIV-1 regions. Therefore, we screened 86 different
      shRNAs targeting highly conserved regions. We identified multiple shRNAs that act
      as potent inhibitors of virus replication. We show, for the first time, that
      expression of three different shRNAs from a single lentiviral vector results in
      similar levels of inhibition per shRNA compared to single shRNA vectors. Thus,
      their combined expression results in a much stronger inhibition of virus
      production. Moreover, when we infected cells transduced with a double shRNA viral
      vector, virus escape was delayed. These results confirm that RNAi has great
      potential as an antiviral gene therapy approach and support our efforts to
      develop this strategy for treatment of HIV-1-infected individuals.

PMID- 16959542
TI  - Quality of life and comorbid medical and psychiatric conditions in temporal lobe
      epilepsy.
AB  - Patients with epilepsy frequently report dissatisfaction with their quality of
      life (QOL), and there is considerable interest in understanding the factors and
      mechanisms associated with this perception. To date, investigation has focused on
      the potential contribution of seizure variables (e.g., seizure control) and
      psychiatric conditions to QOL, but there has not been an examination of the
      potential role of comorbid medical conditions. Information was gathered
      concerning current medical and psychiatric conditions for 93 patients with
      temporal lobe epilepsy, and their relationship with QOL was examined. The numbers
      of medical and psychiatric conditions were distinct and significant predictors of
      QOL satisfaction, and both were stronger correlates than seizure-related factors
      and demographic variables. The implications of these findings for the treatment
      and management of patients with epilepsy are discussed.

PMID- 16959543
TI  - Interactive effects of naphthalene treatment and the onset of vitellogenesis on
      energy metabolism in liver and gonad, and plasma steroid hormones of rainbow
      trout Oncorhynchus mykiss.
AB  - The purpose of the study was to assess in female fish the possible interaction
      between treatment with a polycyclic aromatic hydrocarbon (PAH) like naphthalene
      and the onset of vitellogenesis. In a first experiment, female rainbow trout
      (Oncorhynchus mykiss) at stages 2-3 (previtellogenesis) or 4 (early
      vitellogenesis) were intraperitoneally injected (2 microl g(-1)) with vegetable
      oil alone (control) or containing naphthalene (50 mg kg(-1)) to be sampled 3 h
      later. A second experiment was similarly designed but using fish
      intraperitoneally implanted (10 microl g(-1)) with slow-release coconut oil
      implants alone (control) or containing 50 mg naphthalene kg(-1) body mass that
      were sampled 3 days after injection. On each sampling time, plasma levels of
      cortisol and 17beta-estradiol, and several metabolic parameters in plasma, liver
      and gonad were assessed. In controls, early vitellogenic fish compared with
      previtellogenic fish displayed changes that in some cases are confirmatory of
      previous studies whereas in other cases provide new information in plasma
      (increased amino acid levels), liver (decreased capacity for exporting glucose
      and reduced amino acid levels) and gonad (decreased amino acid levels).
      Naphthalene treatment produced in previtellogenic fish decreased 17beta-estradiol
      levels in plasma, increased plasma glucose or decreased liver gluconeogenic
      capacity whereas no major effects were noticed on parameters involved in lipid,
      amino acid and lactate metabolism. Differential effects of naphthalene treatment
      were noticed in early vitellogenic fish such as decreased 17beta-estradiol and
      glucose levels in plasma, increased hexokinase and glucokinase and lack of
      changes in fructose 1,6-bisphosphatase activities in liver, and a lower decrease
      of amino acid levels in gonad. Those alterations produced by naphthalene
      treatment resulted in a decreased capacity for covering the energy demand of
      vitellogenesis in liver and gonad that could contribute to a delay and/or
      impairment of the onset of maturation.

PMID- 16959544
TI  - Role of calcium channels in cadmium-induced disruption of cortisol synthesis in
      rainbow trout (Oncorhynchus mykiss).
AB  - The mechanisms of toxicity of cadmium (Cd(2+)) in adrenal steroidogenesis were
      investigated in vitro in adrenocortical cells of rainbow trout (Oncorhynchus
      mykiss). Toxicity of Cd(2+) was increased in absence of extracellular Ca(2+), but
      was prevented in Ca(2+)-supplemented medium. Pretreatment of cells with BAY K8644
      (BAY), an agonist of voltage-dependent calcium channels, increased the Cd(2+)
      mediated inhibition of ACTH-stimulated secretion but not pregnenolone (PREG)
      stimulated secretion. Nicardipine, an antagonist of voltage-dependent calcium
      channels, also increased the inhibition of adrenocorticotropic hormone (ACTH)
      stimulated secretion by Cd(2+). These results suggest that opening of voltage
      dependent calcium channels with BAY may allow Cd(2+) entry at the same time as
      calcium, thus increasing toxicity of Cd(2+), however voltage-dependent calcium
      channels may not be the only way of entry into adrenocortical cells. The influx
      of Cd(2+), measured as intracellular Cd(2+) using Fluo-3 in PREG-stimulated
      adrenocortical cells, was significantly enhanced by the stimulation. These
      results suggest that the deleterious effect of Cd(2+) on cortisol steroidogenesis
      may be enhanced when the endocrine stress response is triggered.

PMID- 16959545
TI  - Inhaled activated protein C attenuates lung injury induced by aerosolized
      endotoxin in mice.
AB  - The serine protease activated protein C (APC) possesses prominent anticoagulant
      and anti-inflammatory actions. In this study, we investigated the effect of
      inhaled recombinant human (rh) APC in a murine lung injury model. Animals inhaled
      10 mg of Pseudomonas lipopolysaccharide (LPS) in 3 mL normal saline (NS); 30 min
      prior to LPS, mice were pretreated with inhaled rhAPC (4 mg/3 mL NS; APC+LPS
      group) or NS (LPS group). A control animal group inhaled vehicle (NS) twice. 24 h
      later, total cells and cell-types, protein content, and the cytokines tumor
      necrosis factor-alpha, interleukin (IL)-6, macrophage inflammatory protein
      1alpha, and mouse keratinocyte-derived chemokine (a homolog of human IL-8) were
      estimated in bronchoalveolar lavage fluid (BALF). Lung pathology given as total
      histology score (THS), wet/dry lung weight ratios, and lung vascular cell
      adhesion molecule (VCAM)-1 expression were additionally assessed. rhAPC
      inhalation attenuated the aerosolized LPS-induced increases of: total cells,
      neutrophils and macrophages in BALF, lung tissue VCAM-1 protein levels, and THS.
      Total protein levels and cytokines in BALF, and wet/dry weight ratios were
      increased in the LPS group, but rhAPC pretreatment did not significantly alter
      the LPS-induced responses. In conclusion, in this murine septic model of lung
      injury, inhaled rhAPC appears to attenuate lung inflammation, without reversing
      the observed increases in lung permeability and BALF cytokines. This effect may
      be associated with leukocyte trafficking modifications, related, at least in
      part, to VCAM-1 reduction.

PMID- 16959546
TI  - Role of AT1 receptors in permeability of the blood-brain barrier in diabetic
      hypertensive rats.
AB  - The precise mechanisms of vascular diseases in patients with diabetic
      hypertensive are not clearly understood. There are evidences of alteration in
      permeability of blood-brain barrier (BBB) in diabetic hypertensive rats. This
      study sought to examine the effect of candesartan on the systolic blood pressure
      and the brain endothelial barrier function and antioxidant enzymes in rat brain.
      Five groups of eight male Sprague-Dawley rats include: control group (gpI),
      diabetic hypertensive group (gpII), diabetic hypertensive group treated with
      candesartan (gpIII), diabetic hypertensive rats with epinephrine (gpIV) and
      diabetic hypertensive rats with epinephrine treated with candesartan (gpV).
      Diabetes was induced by single injection of 55 mg kg(-1) streptozotocin (STZ)
      i.p. Blood glucose was measured, rats with blood glucose higher than 300 mg/dl
      were identified as diabetic. After induction of diabetes, rats received L-NAME
      (0.5 mg/ml in drinking water for 1 week) starting on the day 4 after STZ
      injection. Systolic blood pressure (SBP) was recorded two times, at day 0 (before
      starting L-NAME) and at day 7 (after L-NAME treatment). Also, body weight was
      measured two times, at initial time (before STZ injection) and terminal (at the
      last day in the experiment). On the day of acute experiment, rats were
      anesthetized with sodium pentobarbital (35 mg/kg, i.p.). The integrity of the BBB
      was investigated using Evans blue (EB) dye (4 ml/kg, 2%). Epinephrine was used
      (40 micro g/kg) to increase the permeability of the brain. After decapitation,
      first the brain was removed, next homogenized and then the content of EB dye in
      the brain was measured. Another five groups of rats manipulated with the same
      manner except EB dye injection. These second group to evaluate antioxidant
      enzymes, reduced glutathione (GSH), lipid peroxides and superoxide dismutase
      (SOD) in brain homogenate. This study indicates that, in diabetic hypertensive
      rats, epinephrine administration leads to increase in microvascular-EB-albumin
      efflux to brain. However, candesartan treatment significantly attenuates this
      permeability to brain tissue and significantly increased GSH and SOD activity,
      while level of lipid peroxides was decreased significantly. The finding supports
      that the use of candesartan may offer a good alternative in the treatment of
      diabetic hypertensive subjects because it has an action that might be mediated
      through an antioxidant effect and beneficial effects on vascular endothelial
      permeability as well.

PMID- 16959547
TI  - Antiproliferative effect of millimeter radiation on human erythromyeloid leukemia
      cell line K562 in culture: ultrastructural- and metabolic-induced changes.
AB  - In the present study we compared the proliferation behavior, the ultrastructural
      morphology and the glycolitic metabolism of K562 cells irradiated by low-power
      wide-band millimeter waves, with those of sham-exposed K562 cells (control),
      maintained in the same culture conditions. The gigaHertz radiation treatments,
      performed between 53-78 10(9) Hz, induced a noticeable inhibition of the cell
      proliferation that could be related to relevant ultrastructural changes. Such
      effects brought the irradiated cell system to lose the homeostasis and to trigger
      defense/reparatory mechanisms in order to reestablish a new steady state. (13)C
      Nuclear magnetic resonance data on the kinetic of glucose metabolism demonstrated
      that the irradiated cells enhanced the glycolitic aerobic pathway, indicating
      that such system need to produce an extra-bioenergy. Most of the ATP synthesized
      served probably to perform the above processes resulting in a significant
      decrease of the proliferation rate without significant cell death increment.

PMID- 16959549
TI  - Effects of combined cholinergic-purinergic block upon cat carotid body
      chemoreceptors in vitro.
AB  - Since acetylcholine (ACh) and ATP have been proposed as excitatory co
      transmitters at synapses between glomus cells and sensory nerve endings of the
      carotid body (CB), we tested such hypothesis by studying the effects of combined
      cholinergic-purinergic block on the chemosensory activity recorded from cat's
      carotid bodies perfused and/or superfused in vitro. The preparations were bathed
      with Tyrode's solution, either normoxic (PO2=98.5+/-13.5 Torr) or hypoxic
      (PO2=31.8+/-5.2 Torr), and the frequency of chemosensory impulses (fchi) was
      recorded from the carotid (sinus) nerve. Dose-response curves for fchi increases
      evoked by intra-stream boluses of acetylcholine, nicotine and ATP were studied. A
      combination of mecamylamine 2 microM and suramin 50 microM, applied through the
      perfusate or superfusate, suppressed nicotine- and ATP-induced increases in fchi,
      but the basal chemosensory activity in normoxia and the chemosensory excitation
      elicited by hypoxic superfusion were preserved, although variably reduced in most
      preparations. Thus, in spite of the excitatory effects provoked by applying ACh
      and ATP to the perfused/superfused CB in vitro, a co-release of these substances
      cannot account entirely for the chemosensory excitation induced by hypoxic
      stimulation of the CB.

PMID- 16959548
TI  - Iron chelators reduce chromosomal breaks in ataxia-telangiectasia cells.
AB  - Ataxia-telangiectasia (A-T) is characterized by ataxia, genomic instability, and
      increased cancer incidence. Previously, iron chelator concentrations which
      suppressed normal cell colony formation increased A-T cell colony formation.
      Similarly, iron chelators preferentially increased A-T cell colony formation
      following peroxide exposure compared to normal cells. Last, A-T cells exhibited
      increased short-term sensitivity to labile iron exposure compared to normal
      cells, an event corrected by recombinant ATM (rATM) expression. Since chromosomal
      damage is important in A-T pathology and iron chelators exert beneficial effects
      on A-T cells, we hypothesized that iron chelators would reduce A-T cell
      chromosomal breaks. We treated A-T, normal, and A-T cells expressing rATM with
      labile iron, iron chelators, antioxidants, and t-butyl hydroperoxide, and
      examined chromosomal breaks and ATM activation. Additionally, the effect of ATM
      deficiency on transferrin receptor (TfR) expression and TfR activity blockage in
      A-T and syngeneic A-T cells expressing rATM was examined. We report that (1) iron
      chelators and iron-free media reduce spontaneous and t-butyl hydroperoxide
      induced chromosomal breaks in A-T, but not normal, or A-T cells expressing rATM;
      (2) labile iron exposure induces A-T cell chromosomal breaks, an event lessened
      with rATM expression; (3) desferal, labile iron, and copper activate ATM; (4) A-T
      cell TfR expression is lowered with rATM expression and (5) blocking TfR activity
      with anti-TfR antibodies increases A-T cell colony formation, while lowering
      chromosomal breaks. ATM therefore functions in iron responses and the maintenance
      of genomic stability following labile iron exposure.

PMID- 16959550
TI  - Genetic CLC-1 chloride channel deficiency modifies diaphragm muscle isometric
      contractile properties.
AB  - Genetic deficiency of the muscle chloride channel CLC-1 leads to myotonia
      congenita in humans as well as myotonia in mice and goats. The hallmark of
      myotonia is delayed muscle relaxation due to persistent electrical discharges in
      the muscle. The present study tested the hypothesis that performance of CLC-1
      deficient diaphragm muscle is also altered during the contractile phase of the
      contraction-relaxation cycle. Diaphragm of CLC-1 deficient and wild type mice
      underwent in vitro isometric contractility testing. Myotonia was easily
      demonstrable during contractions elicited by train stimulation, but was not seen
      during twitch stimulation or during train stimulation preceded by a series of
      twitch stimulations. Twitch force was reduced from 16.7+/-2.5 N/cm(2) in normal
      muscle to 7.2+/-1.9 N/cm(2) in CLC-1 deficient muscle (P<0.002). Isometric twitch
      contraction time was shortened from 19.6+/-0.9 to 15.7+/-1.0 ms (P<0.002). During
      repetitive 25 Hz stimulation, force/area was lower for diseased than normal
      muscle, whereas force as a percent of initial values declined at a faster rate
      for normal than diseased muscle. The latter could be accounted for by a rightward
      shift in the force-frequency relationship of CLC-1 deficient relative to normal
      muscle, as use of stimulation frequencies which elicited comparable force levels
      as a percentage of maximum 100 Hz tetanic force led to similar rates of fatigue.
      These findings indicate that genetic CLC-1 deficiency not only affects muscle
      relaxation (myotonia) but also modulates diaphragm performance during the
      contractile phase of the contraction-relaxation cycle.

PMID- 16959551
TI  - Sensitive determination of aspirin and its metabolites in plasma by LC-UV using
      on-line solid-phase extraction with methylcellulose-immobilized anion-exchange
      restricted access media.
AB  - We describe a sensitive determination of aspirin (ASA) and its three metabolites
      (salicylic acid [SA], 2,3-dihydroxybenzoic acid [2,3-DHBA], and 2,5
      dihydroxybenzoic acid [gentisic acid (GA)]) in rat plasma. Analysis was carried
      out by on-line solid-phase extraction (SPE) using a methylcellulose-immobilized
      strong anion-exchanger (MC-SAX), followed by liquid chromatography (LC) coupled
      with UV detection. The lower limits of quantitation for ASA and SA were 60 ng/mL
      in 100 microL of plasma, respectively. This method was validated with respect to
      intra- and inter-day precision, accuracy, and linearity up to concentrations of
      20,000 ng/mL for ASA, SA, 2,3-DHBA and gentisic acid, respectively. The method
      was successfully applied to an analysis of the pharmacokinetics of ASA and SA in
      rats.

PMID- 16959552
TI  - Sensitive quantification of ranolazine in human plasma by liquid chromatography-
      tandem mass spectrometry with positive electrospray ionization.
AB  - A rapid, selective and sensitive liquid chromatography-tandem mass spectrometry
      (LC-MS-MS) method with positive electrospray ionization (ESI) was developed for
      the quantification of ranolazine in human plasma. After liquid-liquid extraction
      of ranolazine and internal standard (ISTD) phenoprolamine from a 100 microl
      specimen of plasma, HPLC separation was achieved on a Nova-Pak C(18) column,
      using acetonitrile-water-formic acid-10% n-butylamine (70:30:0.5:0.08, v/v/v/v)
      as the mobile phase. The mass spectrometer was operated in multiple reaction
      monitoring (MRM) mode using the transition m/z 428.5-->m/z 279.1 for ranolazine
      and m/z 344.3-->m/z 165.1 for the internal standard, respectively. Linear
      calibration curves were obtained in the concentration range of 5-4000 ng/ml, with
      a lower limit of quantitation (LLOQ) of 5 ng/ml. The intra- and inter-day
      precision values were below 3.7% and accuracy was within +/-3.2% at all three
      quality control (QC) levels. This method was found suitable for the analysis of
      plasma samples collected during the phase I pharmacokinetic studies of ranolazine
      performed in 28 healthy volunteers after single oral doses from 200 mg to 800 mg.

PMID- 16959553
TI  - Purification by expanded bed adsorption and characterization of an alpha-amylases
      FORILASE NTL from A. niger.
AB  - In this work the purification and biochemistry characterization of alpha-amylases
      from Aspergillus niger (FORILASE NTL) were studied. The effects of expansion
      degree of resin bed on enzyme purification by expanded bed adsorption (EBA) have
      also been studied. Residence time distributions (RTD) studies were done to
      achieve the optimal conditions of the amylases recovery on ion-exchange resin,
      and glucose solution was used as a new tracer. Results showed that height
      equivalent of the theoretical plates (HETP), axial dispersion and the Prandt
      number increased with bed height, bed voidage and linear velocity. The adsorption
      capacity of alpha-amylases, on the resin, increased with bed height and the best
      condition was at four-expansion degree. alpha-Amylase characterization showed
      that this enzyme has high affinity with soluble starch, good hydrolysis potential
      and molecular weight of 116 kDa.

PMID- 16959554
TI  - Direct on-membrane peptide mass fingerprinting with MALDI-MS of tyrosine
      phosphorylated proteins detected by immunostaining.
AB  - We have identified tyrosine-phosphorylated proteins on membrane from A-431 human
      epidermoid carcinoma cells by using detection with anti-phosphotyrosine antibody
      followed by PMF analysis. In there, on-membrane digestion for these protein spots
      was carried out on microscale region using chemical inkjet technology and the
      resulting tryptic digests were directly analyzed by MALDI-TOF MS. Proteins
      identified by a database search included phosphoproteins that are known to be
      markedly phosphorylated on tyrosine sites after the cells are treated with
      epidermal growth factor (EGF). This procedure is a rapid and easily handled
      approach that enables both detection and identification of phosphoproteins on a
      single blot membrane.

PMID- 16959555
TI  - Fetal brain monitoring: future applications.
AB  - Future application of fetal brain monitoring is explored by selecting and
      analysing articles for information on types of brain damage that can be
      monitored, where in the brain this can be done, how long after the risk exposure,
      and with what method of investigation. A limited number of--mainly--case
      histories reported that early (cell death and oedema) and late (gliosis) effects
      of brain damage can be demonstrated before birth with multiplanar ultrasound and
      magnetic resonance imaging, and that hypoxic ischaemic injury or infection can
      induce local or widespread brain injury, occurring as transient or longer-lasting
      changes in age-related predilection areas for which normal features are known.
      The antenatal role of risk factors inducing abnormal brain development can be
      studied longitudinally with ultrasound and magnetic resonance imaging. A
      multidisciplinary approach will facilitate the introduction of various techniques
      with adequate know-how of underlying processes, to evaluate the predictive value
      on neurological outcome and prevent premature introduction into clinical
      application.

PMID- 16959556
TI  - Is near-infrared spectroscopy living up to its promises?
AB  - The first clinical application of near-infrared spectroscopy (NIRS) was made 20
      years ago on the head of newborn infants under intensive care. Since then NIRS
      has yielded much credible and some important clinical research data. The most
      important results have been obtained using the cumbersome but quantitative
      techniques for measuring cerebral blood flow, cerebral blood volume, or venous
      oxygen saturation with manipulation of FiO(2) or impeding venous outflow from the
      brain. The continuous nature of NIRS has been combined with monitoring of
      arterial pressure to obtain measures of cerebrovascular regulation, but this
      method has not been applied on a larger scale. Second-generation instruments
      allow a running estimate of vascular haemoglobin oxygen saturation, named the
      tissue oxygenation index (TOI), in absolute terms. Applied to the head, this is a
      surrogate measure of cerebro-venous saturation, an important variable in neuro
      intensive care. The precision, however, is insufficient to be useful. IN
      CONCLUSION: clinical application is not in sight.

PMID- 16959557
TI  - Research collaborations: trial, trust, and truth.
AB  - Successful advances in biomedical research increasingly require multigroup
      collaborations and publication of results in multiauthored papers. It is
      essential to consider at the outset how to maximize the value of such
      collaborations while avoiding potential pitfalls.

PMID- 16959558
TI  - Targeting protein stability with a small molecule.
AB  - Both genetic approaches and small-molecule inhibitors can be used to perturb
      protein function. Banaszynski et al. (2006) now describe a strategy to regulate
      the stability of a target protein, in which specificity is provided by a
      genetically encoded tag and temporal control is imparted by a small molecule.

PMID- 16959559
TI  - Signaling by transmembrane proteins shifts gears.
AB  - The HAMP domain is present in a large number of transmembrane proteins in
      prokaryotes including histidine kinases, adenylyl cyclases, chemotaxis receptors,
      and phosphatases. In this issue of Cell, Hulko et al. (2006) report the NMR
      structure of a HAMP domain and present data suggesting that it transduces signals
      through a simple rotation of its four-helix parallel coiled coil.

PMID- 16959560
TI  - Plant pathogens trick guard cells into opening the gates.
AB  - The stomata of plants regulate gas exchange and water transpiration in response
      to changing environmental conditions. New work reveals that stomata also have an
      important role in host defense. In this issue of Cell, Melotto et al. (2006) show
      that stomata close upon detection of potential microbial pathogens to prevent the
      infection of the leaf interior. Moreover, pathogenic bacteria have evolved
      strategies to suppress the closure of stomata.

PMID- 16959561
TI  - Mind the GAP: Wnt steps onto the mTORC1 train.
AB  - The TSC1/2 tumor-suppressor complex controls protein synthesis through the
      regulation of mTOR. In this issue of Cell, Inoki et al. (2006) report that the
      kinases GSK3 and AMPK cooperate in the activation of TSC2 to inhibit mTOR
      activity. Surprisingly, the phosphorylation of TSC2 by GSK3 is markedly
      suppressed by Wnt signaling. This suggests that components of the mTOR pathway
      may be therapeutic targets for diseases linked to hyperactive Wnt signaling.

PMID- 16959562
TI  - Insulin secretion: SIRT4 gets in on the act.
AB  - Despite their initial characterization as histone deacetylases controlling
      transcription, sirtuins also turn out to be critical regulators of metabolism. In
      this issue of Cell, Haigis et al. (2006) demonstrate that the mammalian Sir2
      homolog SIRT4 acts in the mitochondria of pancreatic beta cells to repress the
      activity of glutamate dehydrogenase through ADP-ribosylation. In this way, SIRT4
      downregulates insulin secretion by beta cells in response to amino acids.

PMID- 16959563
TI  - Nothing in glycobiology makes sense, except in the light of evolution.
AB  - The remarkable structural diversity of glycans in nature, and their roles in
      cellular processes, host-pathogen interactions, biological diversity and
      speciation can be explained by evolutionary processes.

PMID- 16959564
TI  - Bacterial glycans: key mediators of diverse host immune responses.
AB  - Recent studies have shown that the synthesis of various polysaccharides by
      bacteria can induce immune responses that are beneficial to the bacterium, the
      host, or both. Here, we discuss the diverse interactions between bacterial
      glycans and the host immune system.

PMID- 16959565
TI  - Chemical technologies for probing glycans.
AB  - Glycans are central to many biological processes, but efforts to define their
      functions at the molecular level have been frustrated by a lack of suitable
      technologies. Here we highlight chemical tools that are beginning to address this
      need.

PMID- 16959566
TI  - Glycosylation in cellular mechanisms of health and disease.
AB  - Glycosylation produces an abundant, diverse, and highly regulated repertoire of
      cellular glycans that are frequently attached to proteins and lipids. The past
      decade of research on glycan function has revealed that the enzymes responsible
      for glycosylation-the glycosyltransferases and glycosidases-are essential in the
      development and physiology of living organisms. Glycans participate in many key
      biological processes including cell adhesion, molecular trafficking and
      clearance, receptor activation, signal transduction, and endocytosis. This review
      discusses the increasingly sophisticated molecular mechanisms being discovered by
      which mammalian glycosylation governs physiology and contributes to disease.

PMID- 16959567
TI  - Yersinia virulence depends on mimicry of host Rho-family nucleotide dissociation
      inhibitors.
AB  - Yersinia spp. cause gastroenteritis and the plague, representing historically
      devastating pathogens that are currently an important biodefense and antibiotic
      resistance concern. A critical virulence determinant is the Yersinia protein
      kinase A, or YpkA, a multidomain protein that disrupts the eukaryotic actin
      cytoskeleton. Here we solve the crystal structure of a YpkA-Rac1 complex and find
      that YpkA possesses a Rac1 binding domain that mimics host guanidine nucleotide
      dissociation inhibitors (GDIs) of the Rho GTPases. YpkA inhibits nucleotide
      exchange in Rac1 and RhoA, and mutations that disrupt the YpkA-GTPase interface
      abolish this activity in vitro and impair in vivo YpkA-induced cytoskeletal
      disruption. In cell culture experiments, the kinase and the GDI domains of YpkA
      act synergistically to promote cytoskeletal disruption, and a Y.
      pseudotuberculosis mutant lacking YpkA GDI activity shows attenuated virulence in
      a mouse infection assay. We conclude that virulence in Yersinia depends strongly
      upon mimicry of host GDI proteins by YpkA.

PMID- 16959568
TI  - Crystal structure of the catalytic alpha subunit of E. coli replicative DNA
      polymerase III.
AB  - Bacterial replicative DNA polymerases such as Polymerase III (Pol III) share no
      sequence similarity with other polymerases. The crystal structure, determined at
      2.3 A resolution, of a large fragment of Pol III (residues 1-917), reveals a
      unique chain fold with localized similarity in the catalytic domain to DNA
      polymerase beta and related nucleotidyltransferases. The structure of Pol III is
      strikingly different from those of members of the canonical DNA polymerase
      families, which include eukaryotic replicative polymerases, suggesting that the
      DNA replication machinery in bacteria arose independently. A structural element
      near the active site in Pol III that is not present in nucleotidyltransferases
      but which resembles an element at the active sites of some canonical DNA
      polymerases suggests that, at a more distant level, all DNA polymerases may share
      a common ancestor. The structure also suggests a model for interaction of Pol III
      with the sliding clamp and DNA.

PMID- 16959569
TI  - The structure of T. aquaticus DNA polymerase III is distinct from eukaryotic
      replicative DNA polymerases.
AB  - The crystal structure of Thermus aquaticus DNA polymerase III alpha subunit
      reveals that the structure of the catalytic domain of the eubacterial replicative
      polymerase is unrelated to that of the eukaryotic replicative polymerase but
      rather belongs to the Polbeta-like nucleotidyltransferase superfamily. A model of
      the polymerase complexed with both DNA and beta-sliding clamp interacting with a
      reoriented binding domain and internal beta binding site was constructed that is
      consistent with existing biochemical data. Within the crystal, two C-terminal
      domains are interacting through a surface that is larger than many dimer
      interfaces. Since replicative polymerases of eubacteria and eukaryotes/archaea
      are not homologous, the nature of the replicative polymerase in the last common
      ancestor is unknown. Although other possibilities have been proposed, the
      plausibility of a ribozyme DNA polymerase should be considered.

PMID- 16959570
TI  - Proline isomerization of histone H3 regulates lysine methylation and gene
      expression.
AB  - The cis-trans isomerization of proline serves as a regulatory switch in signaling
      pathways. We identify the proline isomerase Fpr4, a member of the FK506 binding
      protein family in Saccharomyces cerevisiae, as an enzyme which binds the amino
      terminal tail of histones H3 and H4 and catalyses the isomerization of H3 proline
      P30 and P38 in vitro. We show that P38 is necessary for methylation of K36 and
      that isomerization by Fpr4 inhibits the ability of Set2 to methylate H3 K36 in
      vitro. These results suggest that the conformational state of P38, controlled by
      Fpr4, is important for methylation of H3K36 by Set2. Consistent with such an
      antagonistic role, abrogation of Fpr4 catalytic activity in vivo results in
      increased levels of H3K36 methylation and delayed transcriptional induction
      kinetics of specific genes in yeast. These results identify proline isomerization
      as a novel noncovalent histone modification that regulates transcription and
      provides evidence for crosstalk between histone lysine methylation and proline
      isomerization.

PMID- 16959571
TI  - Forespore engulfment mediated by a ratchet-like mechanism.
AB  - A key step in bacterial endospore formation is engulfment, during which one
      bacterial cell engulfs another in a phagocytosis-like process that normally
      requires SpoIID, SpoIIM, and SpoIIP (DMP). We here describe a second mechanism
      involving the zipper-like interaction between the forespore protein SpoIIQ and
      its mother cell ligand SpoIIIAH, which are essential for engulfment when DMP
      activity is reduced or SpoIIB is absent. They are also required for the rapid
      engulfment observed during the enzymatic removal of peptidoglycan, a process that
      does not require DMP. These results suggest the existence of two separate
      engulfment machineries that compensate for one another in intact cells, thereby
      rendering engulfment robust. Photobleaching analysis demonstrates that SpoIIQ
      assembles a stationary structure, suggesting that SpoIIQ and SpoIIIAH function as
      a ratchet that renders forward membrane movement irreversible. We suggest that
      ratchet-mediated engulfment minimizes the utilization of chemical energy during
      this dramatic cellular reorganization, which occurs during starvation.

PMID- 16959572
TI  - The HAMP domain structure implies helix rotation in transmembrane signaling.
AB  - HAMP domains connect extracellular sensory with intracellular signaling domains
      in over 7500 proteins, including histidine kinases, adenylyl cyclases, chemotaxis
      receptors, and phosphatases. The solution structure of an archaeal HAMP domain
      shows a homodimeric, four-helical, parallel coiled coil with unusual interhelical
      packing, related to the canonical packing by rotation of the helices. This
      suggests a model for the mechanism of signal transduction, in which HAMP
      alternates between the observed conformation and a canonical coiled coil. We
      explored this mechanism in vitro and in vivo using HAMP domain fusions with a
      mycobacterial adenylyl cyclase and an E. coli chemotaxis receptor. Structural and
      functional studies show that the equilibrium between the two forms is dependent
      on the side-chain size of residue 291, which is alanine in the wild-type protein.

PMID- 16959573
TI  - SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie
      restriction in pancreatic beta cells.
AB  - Sir2 is an NAD-dependent deacetylase that connects metabolism with longevity in
      yeast, flies, and worms. Mammals have seven Sir2 homologs (SIRT1-7). We show that
      SIRT4 is a mitochondrial enzyme that uses NAD to ADP-ribosylate and downregulate
      glutamate dehydrogenase (GDH) activity. GDH is known to promote the metabolism of
      glutamate and glutamine, generating ATP, which promotes insulin secretion. Loss
      of SIRT4 in insulinoma cells activates GDH, thereby upregulating amino acid
      stimulated insulin secretion. A similar effect is observed in pancreatic beta
      cells from mice deficient in SIRT4 or on the dietary regimen of calorie
      restriction (CR). Furthermore, GDH from SIRT4-deficient or CR mice is insensitive
      to phosphodiesterase, an enzyme that cleaves ADP-ribose, suggesting the absence
      of ADP-ribosylation. These results indicate that SIRT4 functions in beta cell
      mitochondria to repress the activity of GDH by ADP-ribosylation, thereby
      downregulating insulin secretion in response to amino acids, effects that are
      alleviated during CR.

PMID- 16959574
TI  - TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK
      and GSK3 to regulate cell growth.
AB  - Mutation in the TSC2 tumor suppressor causes tuberous sclerosis complex, a
      disease characterized by hamartoma formation in multiple tissues. TSC2 inhibits
      cell growth by acting as a GTPase-activating protein toward Rheb, thereby
      inhibiting mTOR, a central controller of cell growth. Here, we show that Wnt
      activates mTOR via inhibiting GSK3 without involving beta-catenin-dependent
      transcription. GSK3 inhibits the mTOR pathway by phosphorylating TSC2 in a manner
      dependent on AMPK-priming phosphorylation. Inhibition of mTOR by rapamycin blocks
      Wnt-induced cell growth and tumor development, suggesting a potential therapeutic
      value of rapamycin for cancers with activated Wnt signaling. Our results show
      that, in addition to transcriptional activation, Wnt stimulates translation and
      cell growth by activating the TSC-mTOR pathway. Furthermore, the sequential
      phosphorylation of TSC2 by AMPK and GSK3 reveals a molecular mechanism of signal
      integration in cell growth regulation.

PMID- 16959575
TI  - Plant stomata function in innate immunity against bacterial invasion.
AB  - Microbial entry into host tissue is a critical first step in causing infection in
      animals and plants. In plants, it has been assumed that microscopic surface
      openings, such as stomata, serve as passive ports of bacterial entry during
      infection. Surprisingly, we found that stomatal closure is part of a plant innate
      immune response to restrict bacterial invasion. Stomatal guard cells of
      Arabidopsis perceive bacterial surface molecules, which requires the FLS2
      receptor, production of nitric oxide, and the guard-cell-specific OST1 kinase. To
      circumvent this innate immune response, plant pathogenic bacteria have evolved
      specific virulence factors to effectively cause stomatal reopening as an
      important pathogenesis strategy. We provide evidence that supports a model in
      which stomata, as part of an integral innate immune system, act as a barrier
      against bacterial infection.

PMID- 16959577
TI  - A rapid, reversible, and tunable method to regulate protein function in living
      cells using synthetic small molecules.
AB  - Rapid and reversible methods for perturbing the function of specific proteins are
      desirable tools for probing complex biological systems. We have developed a
      general technique to regulate the stability of specific proteins in mammalian
      cells using cell-permeable, synthetic molecules. We engineered mutants of the
      human FKBP12 protein that are rapidly and constitutively degraded when expressed
      in mammalian cells, and this instability is conferred to other proteins fused to
      these destabilizing domains. Addition of a synthetic ligand that binds to the
      destabilizing domains shields them from degradation, allowing fused proteins to
      perform their cellular functions. Genetic fusion of the destabilizing domain to a
      gene of interest ensures specificity, and the attendant small-molecule control
      confers speed, reversibility, and dose-dependence to this method. This general
      strategy for regulating protein stability should enable conditional perturbation
      of specific proteins with unprecedented control in a variety of experimental
      settings.

PMID- 16959576
TI  - Presenilins form ER Ca2+ leak channels, a function disrupted by familial
      Alzheimer's disease-linked mutations.
AB  - Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative
      disorder. Mutations in presenilins 1 and 2 (PS1 and PS2) account for
      approximately 40% of familial AD (FAD) cases. FAD mutations and genetic deletions
      of presenilins have been associated with calcium (Ca(2+)) signaling
      abnormalities. We demonstrate that wild-type presenilins, but not PS1-M146V and
      PS2-N141I FAD mutants, can form low-conductance divalent-cation-permeable ion
      channels in planar lipid bilayers. In experiments with PS1/2 double knockout
      (DKO) mouse embryonic fibroblasts (MEFs), we find that presenilins account for
      approximately 80% of passive Ca(2+) leak from the endoplasmic reticulum.
      Deficient Ca(2+) signaling in DKO MEFs can be rescued by expression of wild-type
      PS1 or PS2 but not by expression of PS1-M146V or PS2-N141I mutants. The ER Ca(2+)
      leak function of presenilins is independent of their gamma-secretase activity.
      Our data suggest a Ca(2+) signaling function for presenilins and provide support
      for the "Ca(2+) hypothesis of AD."

PMID- 16959581
TI  - Hypertension and diabetes: role of the renin-angiotensin system.
AB  - Hypertension is often associated clinically with diabetes as part of the insulin
      resistance syndrome or as a manifestation of renal disease. Elevated systemic
      blood pressure accelerates micro- and macrovascular complications in diabetes.
      Vasoactive hormone pathways including the renin-angiotensin-aldosterone system
      (RAAS) appear to play a pivotal role in the pathogenesis and progression of
      diabetic complications and possible diabetes itself. Recent studies have
      increased our understanding of the complexity of the RAAS with identification of
      new components of this cascade including angiotensin-converting enzyme 2 and a
      putative renin receptor. Agents that interrupt the RAAS confer end-organ
      protection in diabetes via hemodynamic and non-hemodynamic mechanisms. Trials are
      investigating the possible role of RAAS blockade in the prevention of type 2
      diabetes.

PMID- 16959582
TI  - Diabetic dyslipidemia.
AB  - Type 2 diabetes mellitus is associated with a markedly increased risk of
      cardiovascular disease. A complex dyslipidemia, which is an integral part of the
      underlying insulin resistance in this group, is a key to this increased risk.
      Increased secretion of VLDL from the liver is a central feature of dyslipidemia
      and is linked significantly to the low HDL and abnormal LDL that are also
      present. A number of physiologic and pharmacologic approaches are available and
      should be used aggressively to treat diabetic dyslipidemia.

PMID- 16959583
TI  - Receptor for advanced glycation end products and the cardiovascular complications
      of diabetes and beyond: lessons from AGEing.
AB  - The presence of elevated blood glucose levels characterizes the diabetic state.
      Hyperglycemia may be caused by a number of underlying factors; however, the
      consequences of chronically elevated glucose are similar. Both the
      macrovasculature and microvasculature are exquisitely sensitive to the long-term
      effects of elevated blood glucose. Cardiovascular disease remains the leading
      cause of morbidity and mortality in diabetes, regardless of the underlying cause
      of hyperglycemia. Although other substrates, such as DNA, are susceptible to
      glycation, this article addresses the impact of nonenzymatic glycation on the
      proteome. The impact of Advanced Glycation End products (AGEs) on alteration of
      protein function and signal transduction mechanisms contributes to the
      pathogenesis of diabetes complications. This suggests that blocking the
      generation or molecular impact of AGEs may modulate the complications of
      diabetes.

PMID- 16959584
TI  - Molecular and signaling mechanisms of atherosclerosis in insulin resistance.
AB  - Although the prevalence of cardiovascular complications is increased in insulin
      resistant individuals, the underlying causes of this link have been elusive.
      Recent work suggests that several intracellular signal transduction pathways are
      inappropriately activated by hyperinsulinemia, hyperglycemia, increased free
      fatty acids, dyslipidemia, various inflammatory cytokines and adipokines--factors
      that are increased in insulin resistance. Once activated, substantial cross talk
      occurs between these pathways, especially a self-reinforcing cascade of vascular
      inflammation and cell dysfunction, greatly increasing the risk and severity of
      atherosclerosis in the insulin-resistant individual. We review several key cell
      signalling pathways, describe how they are activated in they insulin-resistant
      state and the damage they induce, and discusses possible therapeutic approaches
      to limit vascular damage.

PMID- 16959585
TI  - Endothelial dysfunction and its role in diabetic vascular disease.
AB  - When normal endothelial function is shifted to a pathological degree, the
      foundation is laid for possibly following diseases. This endothelial dysfunction
      is characterized by a proinflammatory state, reduced vasodilation, and a
      prothrombotic state. In the continuation this dysfunction is strongly associated
      cardiovascular morbidity and mortality. Endothelial dysfunction is markedly
      enhanced in type 2 diabetes providing a major pathophysiological cause for the
      massively increased cardiovascular risk of diabetic patients. Subsequently future
      therapeutic approaches for the treatment of diabetic cardiovascular disease
      should target the dysfunctional endothelium first.

PMID- 16959586
TI  - Peroxisome proliferator-activated receptor gamma agonists: their role as
      vasoprotective agents in diabetes.
AB  - Both type 1 and type 2 diabetes melitius are associated with increased
      cardiovascular morbidity, and now affect more than 170 million individuals
      worldwide. The incidence of type 2 diabetes is growing rapidly and now accounts
      for 90 to 95 percent of all diabetes cases. Thiazolidinediones (TZDs) a class of
      insulin sensitizing agents commonly used in the treatment of patients who have
      type 2 diabetes, improve endothelial dysfunction and exert beneficial effects on
      lipid profiles by activating the nuclear receptor peroxisome proliferator
      activated receptor gamma (PPAR-gamma). In addition, TZDs exhibit antiatherogenic
      effects, independent of their antidiabetic and lipid-lowering properties, by
      attenuating proinflammatory processes. The combination of increased insulin
      sensitivity, improved lipid profile, and reduced inflammation may explain the
      cardiovascular benefits of this class of drugs

PMID- 16959587
TI  - Diabetic cardiomyopathy.
AB  - This article focuses on advances in the understanding of the pathogenesis and
      treatment of diabetic cardiomyopathy. Patients with diabetes are at an elevated
      risk for heart failure, and comorbid heart failure confers an increased risk of
      morbidity and mortality. Diabetic cardiomyopathy and to apply proven lifesaving
      therapies in all heart failure patients, including those with diabetes, in the
      absence of contraindications or intolerance.

PMID- 16959588
TI  - Alterations in ion channel physiology in diabetic cardiomyopathy.
AB  - Diabetes mellitus is one of the most common chronic illnesses worldwide. This
      article focuses on a subgroup of diabetic patients with a specific cardiac
      complication of this disease--diabetic cardiomyopathy. This article initially
      gives some general background on diabetic cardiomyopathy and ion channels. Next
      the focus is on how diabetic cardiomyopathy alters calcium homeostasis in cardiac
      myocytes and highlights the specific alterations in ion channel function that are
      characteristic of this type of cardiomyopathy. Finally, the importance of the
      renin-angiotensin system in diabetic cardiomyopathy is reviewed.

PMID- 16959589
TI  - Polycystic ovarian syndrome: the next cardiovascular dilemma in women?
AB  - All known risks for cardiovascular disease are increased in women with polycystic
      ovary syndrome, which features amenorrhea, hirsutism, and obesity. Epidemiologic
      studies in these patients and their families have revealed a familial
      predisposition not only to polycystic ovary syndrome, but also diabetes,
      hypertension, and cardiovascular disease. The heterogeneity of phenotypes
      (clinically and biochemically) leads to difficulty in achieving a precise
      diagnosis, defining a single underlying pathogenesis, and selecting a homogeneous
      population for much needed prospective studies. The authors believe that while
      insulin resistance plays and important role in some cases of polycystic ovarian
      syndrome, it is the overall milieu created by the co-existence of several
      cardiovascular risk factors in polycystic ovarian syndrome patients which could
      be an important target for preventative strategies and therapy.

PMID- 16959590
TI  - Ethnicity and diabetic heart disease.
AB  - Ethnicity is a complex yet important construct and an independent risk factor for
      diabetic heart disease (DHD) with paramount clinical significance. Clinicians
      should try to better understand the role of ethnicity through more questions. The
      risk of DHD is modified by ethnicity through more questions. The risk of DHD is
      modified by ethnicity, and its management may require a culturally sensitive
      individualized approach. Findings from Caucasian populations cannot be fully
      extrapolated to other ethnic groups, thereby emphasizing the importance of future
      research with ethnicity-based threshold for obesity. Available limited data
      support the interaction between genetic predisposition, environmental risk, and
      lifestyle choices and disparities based on ethnicity as the likely cause for
      ethnic variations in DHD.

PMID- 16959591
TI  - Trace elements in rock salt and their bioavailability estimated from solubility
      in acid.
AB  - In this study, 18 partly commercially available samples of rock salt from
      Austria, Germany, Pakistan, Poland, Switzerland, and Ukraine were investigated
      with respect to their content of trace elements using instrumental neutron
      activation analysis. Elements detected were Al, Ba, Br, Ca, Ce, Cl, Co, Cr, Cs,
      Eu, Fe, Hf, La, Mn, Na, Rb, Sb, Sc, Sm, Sr, Ta, Tb, Th, and Zn, some of them only
      in individual cases. An estimation of the bioavailability of these trace elements
      was performed by dissolving an equivalent of the sodium chloride samples in
      diluted hydrochloric acid (simulating stomach acid), filtering off the insoluble
      components, and analyzing the evaporated filtrate. It could be shown that in most
      cases bioactive trace elements like Fe can be found in rock salt in the form of
      almost insoluble compounds and are therefore not significantly bioavailable,
      whereas thorium, for example, was partly bioavailable in two cases. A significant
      contribution to the recommended daily intake of metal trace elements by using
      rock salt for nutrition can be excluded.

PMID- 16959592
TI  - Interspecies variation in yolk selenium concentrations among eggs of free-living
      birds: The effect of phylogeny.
AB  - Birds deposit the trace element selenium (Se) into their eggs because an adequate
      supply of this micronutrient is essential for embryonic development. Although
      there is considerable interest in egg Se with regard to topics as diverse as
      poultry nutrition and environmental pollution, data on the natural levels of Se
      in eggs of free-living avian species are currently very limited. To address this
      lack of information, we measured the yolk Se concentrations in eggs of 14 avian
      species collected in the wild. The concentrations (ng/g wet yolk) varied from 394
      to 2238, with a mean value of 1040. Values (means+/-SD) for eggs from the UK,
      Canada and New Zealand were, respectively, 522+/-192 (3 species), 1194+/-584 (8
      species) and 1147+/-200 (3 species). However, analysis by appropriate statistical
      models indicates that the effect of phylogenetic relatedness among these species
      is so significant that it removes any effect of geographical location. In
      particular, species belonging to the order Passeriformes displayed significantly
      higher yolk Se levels than Non-Passeriforme species. In marked contrast to the
      free-living species, our previously published data indicate that the Se
      concentration in egg yolk of the domestic chicken is only about 100 ng/g wet yolk
      when the birds are maintained on a basal commercial diet without supplementary
      Se. The results reveal an extensive interspecies variation in yolk Se (across a 6
      fold range) for eggs collected from the wild. Nevertheless, the Se concentrations
      in the yolks of all the free-living species were far higher (4-21-fold) than that
      achieved in the yolk of the domestic chicken consuming a standard basal diet.

PMID- 16959593
TI  - Effects of chromium(VI) and vanadium(V) on the lifespan of fish.
AB  - The effect of chromium(VI) on the lifespan of laboratory-reared guppies (Poecilia
      reticulata) has been studied both in the absence and in the presence of the
      antioxidant D-mannitol, and it has been compared with that produced by
      vanadium(V). The three substances used as additives exhibited either a weak (D
      mannitol), a moderate (chromate) or an acute (vanadate) toxicity to fish.
      Vanadate, with LC50 (7 days) = 3.84 x 10(-5) mol/L, was about ten times more
      toxic than chromate, with LC50 (7 days) = 3.42 x 10(-4) mol/L as a single
      additive and 4.27 x 10(-4) mol/L in the presence of d-mannitol. An increasing
      effect on the maximum lifespan of males was observed when the additives studied
      were used at low concentrations, either alone or in a binary combination,
      following the sequence: vanadate (14%) < D-mannitol (41%) < chromate + D-mannitol
      (57%) < chromate (69%). Of these substances, only chromate increased also the
      maximum lifespan of females (72%). The maximum lifespan showed a strong, positive
      correlation with the concentration of chromate for males (P = 0.00008) and a
      weaker, positive correlation (P = 0.116) for females. These results suggest the
      existence of a chemical-hormesis phenomenon that might be subjected to sexual
      genre variability. Both the toxicity and the chemical-hormetic effect provoked by
      chromate were substantially decreased when it was used in combination with d
      mannitol, and the possible causes for this double inhibition are briefly
      discussed.

PMID- 16959594
TI  - Determination of Cd, Cu, Pb and Zn in neoplastic kidneys and in renal tissue of
      fetuses, newborns and corpses.
AB  - The incidence of kidney tumors in USA and Europe (in particular, Central Europe
      and Italy) has been dramatically increasing since the 1970s, possibly as a
      consequence of ongoing environmental pollution. Environmental factors have been
      considered responsible for at least 80% of the incidence of neoplastic diseases.
      To shed some light on this issue, the amounts of Cd and Pb were measured in
      neoplastic tissue and adjacent normal part of kidney excised for carcinoma and
      compared with those in renal tissues of fetuses, newborns and subjects that died
      of non-neoplastic diseases. Cd and Pb were determined by Inductively Coupled
      Plasma Atomic Emission Spectrometry and Atomic Absorption Spectrometry with
      Electrothermal Atomization. Metallothionein immunoperoxidase staining technique
      was used to localize the accumulation of Cd and Zn in the nephrons. Content of Cd
      and Pb in kidneys of fetuses and newborns was extremely low. However, it was
      significantly increased in adjacent-normal tissues of kidneys with carcinomas,
      and significantly higher compared to kidneys of individuals that died of non
      neoplastic diseases. In tumoral tissues of the excised kidneys, Cd content was
      very low, while that of Pb significantly elevated. High amounts of Cd and Pb in
      the adjacent-normal parts of kidneys with carcinomas are suggestive of possible,
      individual or synergistic, effects of these pollutants on enzymatic systems,
      priming an oncogenic pathway. Detection of metallothioneins, primary ligands of
      Cd, exclusively in the cells of proximal tubuli, i.e. wherein renal carcinoma
      develops in over 80% of cases, strongly supports the assumption that Cd exerts a
      carcinogenic effect.

PMID- 16959595
TI  - Antioxidant defense system and cadmium uptake in barley genotypes differing in
      cadmium tolerance.
AB  - Using two barley (Hordeum vulgare) cultivars (cvs. Tokak and Hamidiye) nutrient
      solution experiments were conducted in order to study the genotypic variation in
      tolerance to Cd toxicity based on (i) development of leaf symptoms, (ii)
      decreases in dry matter production, (iii) Cd concentration and (iv) changes in
      antioxidative defense system in leaves (i.e., superoxide dismutase, ascorbate
      peroxidase, glutathione reductase, catalase, ascorbic acid and non-protein SH
      groups). Plants were grown in nutrient solution under controlled environmental
      conditions, and subjected to increasing concentrations of Cd (0, 15, 30, 60 and
      120 micromol/L Cd) for different time periods. Of the barley cultivars Hamidiye
      was particularly sensitive to Cd as judged by the severity and earlier
      development of Cd toxicity symptoms on leaves. Within 48 h of Cd application
      Hamidiye rapidly developed severe leaf Cd toxicity symptoms whereas in Tokak the
      leaf symptoms appeared only slightly. Hamidiye also tended to show more decrease
      in growth caused by Cd supply when compared to Tokak. The differences in
      sensitivity to Cd between Tokak and Hamidiye were not related to Cd
      concentrations in roots and shoots or Cd accumulation per plant. With the
      exception of catalase, activities of the enzymes involved in detoxification of
      reactive oxygen species (ROS) were markedly enhanced in Hamidiye by increasing Cd
      supply. By contrast, in Tokak there was either only a slight increase or no
      change in the activities of the antioxidative enzymes. Similarly, levels of
      ascorbic acid and especially non-protein SH-groups were increased in Hamidiye by
      Cd supply, but not affected in Tokak. The results indicate the existence of a
      large genotypic variation between barley cultivars for Cd tolerance. The
      differential Cd tolerance found in the barley cultivars was not related to uptake
      or accumulation of Cd in plants, indicating importance of internal mechanisms in
      expression of differential Cd tolerance in barley. As a response to increasing Cd
      supply particular increases in antioxidative mechanisms in the Cd-sensitive
      barley cultivar Hamidiye suggest that the high Cd sensitivity of Hamidiye is
      related to enhanced production and oxidative damage of ROS.

PMID- 16959596
TI  - Hypoglycemic activity of fermented mushroom of Coprinus comatus rich in vanadium.
AB  - The hypoglycemic activity of fermented mushroom of Coprinus comatus rich in
      vanadium (CCRV) was studied in this paper. Alloxan and adrenalin induced
      hyperglycemic mice were used in the study. The blood glucose and the HbA1c of the
      mice were analyzed, respectively. At the same time, the sugar tolerance of the
      normal mice was also determined. After the mice were administered (ig) with CCRV,
      the blood glucose and the HbA1c of alloxan-induced hyperglycemic mice decreased
      (p < 0.05, p < 0.01), ascension of blood glucose induced by adrenalin was
      inhibited (p < 0.01) and the sugar tolerance of the normal mice was improved.
      Also, the body weight of the alloxan-induced hyperglycemic mice was increased
      gradually. In the fermented mushroom of C. comatus, vanadium at lower doses in
      combination with C. comatus, induced significant decreases of the blood glucose
      and HbA1c levels in hyperglycemic mice.

PMID- 16959597
TI  - Co-administration of zinc and n-acetylcysteine prevents arsenic-induced tissue
      oxidative stress in male rats.
AB  - Arsenic is a widespread environmental toxicant that may cause neuropathy, skin
      lesions, vascular lesions and cancer upon prolonged exposure. Improving
      nourishment like supplementation of micronutrients, antioxidants, vitamins and
      amino acids could be able to halve the risk in those who were previously the poor
      nourished. The present study was planned to investigate the preventive effects of
      zinc and n-acetylcysteine (NAC) supplementation either alone or in combination
      with arsenic on selected biochemical variables indicative of oxidative stress and
      liver injury in male rats. For 3 weeks 25 male wistar rats were exposed to
      arsenic as sodium arsenite (2 mg/kg, orally through gastric intubation) either
      alone or in combination with NAC (10 mg/kg, intraperitoneally), zinc (5 mg/kg,
      orally) or zinc plus NAC. Animals were sacrificed 24h after the last dosing for
      various biochemical parameters. Concomitant administration of zinc with arsenic
      showed remarkable protection against blood delta-aminolevulinic acid dehydratase
      (ALAD) activity as well as providing protection to hepatic biochemical variables
      indicative of oxidative stress (like thiobarbituric acid reactive substances
      (TBARS) level, catalase) and tissue injury. NAC supplementation on the other
      hand, was moderately effective in protecting animals from the toxic effects of
      arsenic. Interestingly, concomitant administration of zinc and NAC was most
      effective compared to zinc or NAC in eliciting above-mentioned protective
      effects. The above results suggest significant protective value of combined zinc
      and NAC administration in acute arsenic exposure.

PMID- 16959598
TI  - Lead concentrates in ovarian follicle compromises pregnancy.
AB  - Following absorption, lead can concentrate in bodily compartments where it
      disrupts cellular processes and can result in detrimental health consequences.
      The concentration and impact of lead within follicular fluid has not been
      characterized and we used inductively coupled plasma mass spectroscopy (ICP-MS)
      to determine lead levels in blood and follicular fluid from nine patients
      undergoing in vitro fertilization (IVF) treatment. Lead levels within follicular
      fluid were found to be significantly higher in non-pregnant patients compared to
      pregnant patients suggesting that elevated concentrations of the environmental
      toxicant lead adversely affect female reproduction.

PMID- 16959600
TI  - Surgical anatomy of the mandibular region for reconstructive purposes.

PMID- 16959601
TI  - Fibula free flap in mandibular reconstruction.

PMID- 16959602
TI  - Deep circumflex iliac artery free flap in mandible reconstruction.

PMID- 16959603
TI  - Iliac crest grafting for mandibular reconstruction.

PMID- 16959604
TI  - Pectoralis major myocutaneous flap reconstruction of the mandible.

PMID- 16959605
TI  - Costochondral rib grafts in mandibular reconstruction.

PMID- 16959606
TI  - The anterolateral thigh flap in mandibular reconstruction.

PMID- 16959607
TI  - Mutant p53 gain of function: the NF-Y connection.
AB  - The molecular mechanisms underlying mutant p53 gain of function are becoming
      increasingly complex. In this issue of Cancer Cell, Di Agostino et al. identify
      the heterotrimeric transcription factor NF-Y as an interacting partner of mutant
      p53. They show that mutant p53/NF-Y complexes bind to NF-Y target promoters and
      recruit p300 in response to DNA damage, resulting in aberrant transactivation of
      NF-Y target genes and cell cycle deregulation. These data thereby implicate
      transcriptional activation by mutant p53 as a key mechanism responsible for its
      oncogenic activity.

PMID- 16959608
TI  - Reactive oxygen species in cancer cells: live by the sword, die by the sword.
AB  - Reactive oxygen species and tumor biology are intertwined in a complex web,
      making it difficult to understand which came first, whether oxidants are required
      for tumor cell growth, and whether oxidant stress can be exploited
      therapeutically. Evidence suggests that transformed cells use ROS signals to
      drive proliferation and other events required for tumor progression. This confers
      a state of increased basal oxidative stress, making them vulnerable to
      chemotherapeutic agents that further augment ROS generation or that weaken
      antioxidant defenses of the cell. In this respect, it appears that tumor cells
      may die by the same systems they require.

PMID- 16959609
TI  - The DARC side of metastasis: shining a light on KAI1-mediated metastasis
      suppression in the vascular tunnel.
AB  - Tumor cell metastasis to distant organs is an inefficient process that is limited
      in part by recently identified metastasis suppressors. Interactions between tumor
      cells and the surrounding stroma are thought to control much of cancer
      progression. In the August issue of Nature Medicine, demonstrate that specific
      cell surface interactions between the metastasis suppressor KAI1 on tumor cells
      and the decoy cytokine receptor DARC on adjacent vascular cells triggers
      senescence in the tumor cells and suppresses metastasis. These new observations
      demonstrate how metastasis suppressors can relay the restraint imposed by the
      stroma onto disseminating tumor cells.

PMID- 16959610
TI  - Epm2a suppresses tumor growth in an immunocompromised host by inhibiting Wnt
      signaling.
AB  - The genetic mechanisms responsible for increased incidence of lymphoma in
      immunocompromised individuals have not been fully elucidated. We show that, in a
      line of TCR transgenic TG-B mice, an insertional mutation in one allele of the
      Epm2a locus and epigenetic silencing of another led to a high rate of lymphoma
      with early onset. Overexpressing Epm2a suppressed the growth of established tumor
      cells and the development of lymphoma in the TG-B mice, while specific silencing
      of the locus increased tumorigenesis in the immune-deficient host. Downregulation
      of Epm2a expression is widespread among mouse and human lymphoma cell lines.
      Epm2a-encoded laforin is a phosphatase for GSK-3beta and an important repressor
      in the Wnt signaling pathway. Inactivation of Epm2a resulted in increased Wnt
      signaling and tumorigenesis.

PMID- 16959611
TI  - Gain of function of mutant p53: the mutant p53/NF-Y protein complex reveals an
      aberrant transcriptional mechanism of cell cycle regulation.
AB  - This article investigates the mechanistic aspects of mutant p53 "gain of
      function" in response to DNA damage. We show that mutant forms of p53 protein
      interact with NF-Y. The expression of cyclin A, cyclin B1, cdk1, and cdc25C, as
      well as the cdk1-associated kinase activities, is upregulated after DNA damage,
      provoking a mutant p53/NF-Y-dependent increase in DNA synthesis. Mutant p53 binds
      NF-Y target promoters and, upon DNA damage, recruits p300, leading to histone
      acetylation. The recruitment of mutant p53 to the CCAAT sites is severely
      impaired upon abrogation of NF-YA expression. Endogenous NF-Y, mutant p53, and
      p300 proteins form a triple complex upon DNA damage. We demonstrate that aberrant
      transcriptional regulation underlies the ability of mutant p53 proteins to act as
      oncogenic factors.

PMID- 16959612
TI  - C/EBPbeta at the core of the TGFbeta cytostatic response and its evasion in
      metastatic breast cancer cells.
AB  - Breast cancers may evade the growth-inhibitory action of TGFbeta by accumulating
      defects of unknown nature that selectively eliminate cytostatic gene responses.
      We found the transcription factor C/EBPbeta to be essential for TGFbeta induction
      of the cell cycle inhibitor p15INK4b by a FoxO-Smad complex and repression of c
      MYC by an E2F4/5-Smad complex in human epithelial cells. These cytostatic
      responses are selectively missing in metastatic breast cancer cells from half of
      the patients that we tested. The basis for this loss was traced to an excess of
      the C/EBPbeta inhibitory isoform LIP. We suggest that C/EBPbeta plays a key role
      in the coordination of TGFbeta cytostatic gene responses, and its malfunction may
      trigger evasion of these responses in breast cancer.

PMID- 16959613
TI  - Essential role of tuberous sclerosis genes TSC1 and TSC2 in NF-kappaB activation
      and cell survival.
AB  - The TSC1-TSC2 complex has recently been implicated in cell survival responses. We
      observed that NF-kappaB signaling is attenuated in TSC1- and TSC2-deficient MEFs
      concomitant with reduced survival following DNA damage or TNFalpha stimulation.
      Reconstitution of TSC2 expression in TSC2(-/-) MEFs rescued survival in an NF
      kappaB activity-dependent manner. Furthermore, in TSC2(-/-) MEFs, the rapamycin
      mediated inhibition of deregulated mTOR activity restored NF-kappaB activation
      and survival. This rapamycin-mediated effect was reversed by inhibition of NF
      kappaB transcriptional activation or by inhibition of ERK1/2 MAP kinase or PI-3K
      pathways, which lie on signaling cascades that lead to NF-kappaB activation.
      These results provide evidence for a crosstalk between the TSC/Rheb/mTOR pathway
      and the NF-kappaB induction pathways and indicate that NF-kappaB functions as an
      important survival factor that regulates TSC2-dependent cell survival.

PMID- 16959614
TI  - ILEI: a cytokine essential for EMT, tumor formation, and late events in
      metastasis in epithelial cells.
AB  - Erk/MAPK and TGFbeta signaling cause epithelial to mesenchymal transition (EMT)
      and metastasis in mouse mammary epithelial cells (EpH4) transformed with
      oncogenic Ras (EpRas). In trials to unravel underlying mechanisms, expression
      profiling for EMT-specific genes identified a secreted interleukin-related
      protein (ILEI), upregulated exclusively at the translational level. Stable
      overexpression of ILEI in EpH4 and EpRas cells caused EMT, tumor growth, and
      metastasis, independent of TGFbeta-R signaling and enhanced by Bcl2. RNAi
      mediated knockdown of ILEI in EpRas cells before and after EMT (EpRasXT)
      prevented and reverted TGFbeta-dependent EMT, also abrogating metastasis
      formation. ILEI is overexpressed and/or altered in intracellular localization in
      multiple human tumors, an event strongly correlated to invasion/EMT, metastasis
      formation, and survival in human colon and breast cancer.

PMID- 16959615
TI  - Selective killing of oncogenically transformed cells through a ROS-mediated
      mechanism by beta-phenylethyl isothiocyanate.
AB  - Reactive oxygen species (ROS) stimulate cell proliferation and induce genetic
      instability, and their increase in cancer cells is often viewed as an adverse
      event. Here, we show that such abnormal increases in ROS can be exploited to
      selectively kill cancer cells using beta-phenylethyl isothiocyanate (PEITC).
      Oncogenic transformation of ovarian epithelial cells with H-Ras(V12) or
      expression of Bcr-Abl in hematopoietic cells causes elevated ROS generation and
      renders the malignant cells highly sensitive to PEITC, which effectively disables
      the glutathione antioxidant system and causes severe ROS accumulation
      preferentially in the transformed cells due to their active ROS output. Excessive
      ROS causes oxidative mitochondrial damage, inactivation of redox-sensitive
      molecules, and massive cell death. In vivo, PEITC exhibits therapeutic activity
      and prolongs animal survival.

PMID- 16959616
TI  - Utility of thyroid transcription factor-1 expression in the differential
      diagnosis of metastatic adenocarcinoma of serous effusion specimens prepared
      using the cell transfer technique.
AB  - BACKGROUND/PURPOSE: Pulmonary adenocarcinoma is a common malignancy of the
      pleural cavity. The cell transfer technique can be used to create multiple slides
      from a single smear. The goal of this study was to investigate the pulmonary
      origin of metastatic adenocarcinoma by evaluating the immunocytochemical
      reactivity to thyroid transcription factor-1 (TTF-1) of slides of serous effusion
      specimens prepared by the cell transfer technique. METHODS: In 2001, a total of
      76 archived serous effusion specimens containing adenocarcinoma from patients
      were used in this study. The primary site of metastatic adenocarcinoma was
      determined by a review of the medical records. The cell transfer technique was
      used to create multiple slides from a single Papanicolaou-stained smear. If more
      than 10% of the target cells reacted with perceptible intensity, nuclear staining
      was considered to indicate a positive TTF-1 result. RESULTS: Positive rates of
      TTF-1 for body fluids collected from patients with lung, stomach, ovarian,
      breast, colorectal and liver carcinomas were 41/50, 0/11, 0/6, 0/5, 0/2 and 0/1,
      respectively. Lung adenocarcinoma showed TTF-1 positivity in 82% of specimens,
      and all other adenocarcinomas had negative TTF-1 staining results. CONCLUSION:
      This study demonstrated that TTF-1 immunostaining in serous effusion specimens
      prepared using the cell transfer technique is a sensitive and highly specific
      marker for metastatic lung adenocarcinoma.

PMID- 16959617
TI  - Clinicopathologic characteristics of Rosai-Dorfman disease in a medical center in
      northern taiwan.
AB  - BACKGROUND/PURPOSE: Rosai-Dorfman disease (RDD) is a rare histiocytic
      proliferative disorder that usually presents as cervical lymphadenopathy.
      Extranodal involvement occurs in up to 40% of patients. The disease is most
      prevalent in blacks and rare in Asians. This study analyzed the characteristics
      of RDD in patients from Taiwan. METHODS: Fourteen patients with a diagnosis of
      RDD were identified by review of records from 1995 to 2004 at National Taiwan
      University Hospital. Tissue sections from each patient were reviewed and
      immunohistochemical staining was performed. Data on clinical presentations,
      associated diseases, treatment and outcome were analyzed. In situ hybridization
      for Epstein-Barr virus (EBV)-encoded small RNAs (EBER-1) was also performed. Sets
      of primers specific for the conservative region of bacterial 16S-rDNA, IS6110 of
      Mycobacterium tuberculosis complex and consensus region of human herpes virus
      (HHV) DNA polymerase genome were used to detect the presence of these infectious
      agents in the specimens. RESULTS: There were six men and eight women with a mean
      age of onset of 44 years. Nine patients presented with skin lesions, four with
      lymph node involvement and one with nasal tumor. All lesions followed a chronic
      and indolent course. Most of the lesions regressed spontaneously, and no patients
      died as a result of this disease during follow-up. Three patients had associated
      immune-mediated disease, i.e. hemolytic anemia, ankylosing spondylitis and
      asthma. Two patients had a history of tuberculosis. Histologically, all lesions
      were characterized by a mixed infiltrate of large pale histiocytes, abundant
      plasma cells and lymphocytes regardless of the site of involvement. The strong
      immunoreactivities of these histiocytes to S-100 protein, CD68 and CD14 with
      occasional lymphophagocytosis were helpful in confirming the diagnosis,
      polymerase chain reaction analysis of 16S-rDNA, IS6110 and HHV gene and in situ
      hybridization for EBV were all negative. CONCLUSION: RDD in Taiwan is
      characterized by older age of onset compared to Western countries (44 years vs.
      20 years) and more frequent extranodal involvement. The skin was the most common
      site of extranodal involvement, with about two-thirds of patients presenting with
      cutaneous lesions. There was no evidence of bacterial, mycobacterial or HHV
      infection in this series.

PMID- 16959618
TI  - Double-blind randomized parallel group study comparing the efficacy and safety of
      tiotropium and ipratropium in the treatment of COPD patients in Taiwan.
AB  - BACKGROUND/PURPOSE: To compare the efficacy and safety of tiotropium and
      ipratropium in patients with chronic obstructive pulmonary disease (COPD) in
      Taiwan. METHODS: This double-blind, randomized, placebo-controlled, parallel
      group study was conducted at six hospitals in Taiwan. COPD patients aged > or =
      40 years, with a forced expiratory volume in 1 second (FEV1) < or = 65% of
      predicted and FEV1/forced vital capacity (FVC) < or = 70% were enrolled. After a
      2-week screening/baseline period, 132 patients were randomized to receive 4 weeks
      of treatment with either tiotropium 18 microg once daily from a dry powder
      inhaler (HandiHaler) or two puffs of ipratropium 20 microg four times daily from
      a metered dose inhaler. The primary outcome was the change in trough FEV1 from
      baseline to week 4. The secondary outcome measures were trough FVC response, FEV1
      and FVC responses at 2 hours postinhalation. RESULTS: After 4 weeks, trough FEV1
      had increased by 61.7 +/- 25.3 mL for tiotropium but decreased by 16.4 +/- 27.9
      mL for ipratropium. The difference between groups was significant (p < 0.05; 95%
      CI, 10-146.1). The trough FVC also increased by 137.2 +/- 49.3 mL for tiotropium
      but was decreased by 84.5 +/- 54.5 mL for ipratropium (p < 0.001; 95% CI, 89.0
      354.3). No major drug-related adverse events associated with tiotropium and
      ipratropium were observed. CONCLUSION: Tiotropium 18 microg once daily using
      HandiHaler was significantly more effective than ipratropium 40 microg four times
      daily in improving trough FEV1 and FVC over a 4-week period. The safety profiles
      of both drugs are comparable.

PMID- 16959619
TI  - Less invasive mitral valve surgery via right minithoracotomy.
AB  - BACKGROUND/PURPOSE: Current trends in cardiac surgical intervention are moving
      toward less invasiveness, with smaller wound or sternum-sparing, less pump time
      or off-pump, and beating rather than arrested heart. Data on the efficacy and
      safety of these newer less invasive techniques, as well as their cosmetic
      results, are limited. This study analyzed the results of a sternum-sparing mitral
      valve operation. METHODS: Thirty patients with mitral valve diseases, including
      20 who underwent mitral valve repair and 10 mitral valve replacement, were
      enrolled. Cardiopulmonary bypass was established via femoral cannulation, and
      blood cardioplegic arrest was induced by using a percutaneous, transthoracic
      cross-clamp. The main surgical wound was made over the lateral border of the
      right breast. Two additional small wounds were required for the transthoracic
      aortic clamp and the mitral retractor. RESULTS: There was no operative mortality,
      and all patients had an uneventful recovery. Two patients underwent redo mitral
      surgery. Nine associated procedures were performed including tricuspid valve
      annuloplasty in six patients, tricuspid valve replacement in two patients and
      atrial septal defect repair in one patient. The length of the main wound was
      between 5.8 and 7.8 cm (mean, 7.1 cm). The mean cardiopulmonary bypass time and
      cross-clamp time were 91.1 and 43.7 minutes, respectively. Although the length of
      stay was not significantly reduced compared with traditional median sternotomy,
      all patients had satisfactory results with good cosmesis. CONCLUSION: Sternum
      sparing mitral valve surgery appears to be a safe and effective alternative to
      conventional mitral valve surgery; it is less invasive and provides superior
      cosmetic results for patients.

PMID- 16959620
TI  - Effect of availability of a parturient-elective regional labor pain relief
      service on the mode of delivery.
AB  - BACKGROUND/PURPOSE: Regional analgesia for labor pain relief is effective and
      widely used. This study evaluated the controversial association between mode of
      operative delivery and patient-elective labor regional analgesia. METHODS: We
      retrospectively compared the rates of instrumental vaginal and cesarean
      deliveries in parturients before the introduction, in the first 15 months after,
      and in the subsequent 36 months after the implementation of an elective labor
      regional analgesia service. A total of 9779 low-risk singleton cephalic
      pregnancies above 36 weeks of gestation were included. The maternal and fetal
      outcomes for parturients before the service was implemented and in those with or
      without pain relief service in the two postimplementation periods were analyzed.
      Multivariate logistic regression analyses were used to investigate the effects of
      maternal age, gestational weeks and newborn weight, in addition to regional
      analgesia, on the mode of delivery in nulliparous women. RESULTS: After adjusting
      for maternal age, gestational weeks, and newborn weight, no significant
      association was found between regional analgesia and cesarean delivery in
      nulliparas. Further, this lack of association was not affected by the receipt of
      regional analgesia in the early period of program implementation or in the period
      after staff had become familiar with the service. A higher rate of instrumental
      vaginal delivery was noted in nulliparas given regional analgesia. CONCLUSION:
      Regional analgesia for pain relief increased the likelihood of instrumental
      vaginal delivery, but did not increase the likelihood of cesarean delivery.

PMID- 16959621
TI  - Changes and factors influencing health-related quality of life after hysterectomy
      in premenopausal women with benign gynecologic conditions.
AB  - BACKGROUND/PURPOSE: A hysterectomy affects a woman's health. This study was
      performed to identify the factors that affect health-related quality of life
      (HRQoL) before and after hysterectomy in premenopausal women. METHODS: This
      prospective follow-up study recruited 38 women (age range, 33-52 years) who
      underwent abdominal hysterectomy for nonmalignant causes. SF-36 and self-rated
      health status were used to assess HRQoL before and after hysterectomy. Data were
      analyzed using descriptive statistics, nonparametric tests and the generalized
      estimating equation method for modeling the repeatedly measured responses.
      RESULTS: Patients' attitudes toward hysterectomy and subsequent sexual activity
      were influenced by the surgery. All patients showed significant improvements in
      the physical component summary (PCS) of SF-36 (mean, 42.1-51.0), but there was no
      significant difference in the mental component summary (MCS). The significant
      improvements were found from the five repeated measurements of the self-rated
      health status (mean, 6.0-7.3). Hemoglobin level was the most important predictor
      of HRQoL before surgery. Women in employment, with more years of education and
      previous blood transfusion had high MCS scores after surgery. CONCLUSION: The
      overall self-rated health status and PCS showed significant improvements after
      hysterectomy. Having had a blood transfusion, being educated and employed were
      positively associated with MCS score after surgery. These findings are vital for
      preoperative counseling for women undergoing hysterectomy.

PMID- 16959622
TI  - Safety and effectiveness of rosiglitazone in type 2 diabetes patients with
      nonalcoholic Fatty liver disease.
AB  - BACKGROUND/PURPOSE: Nonalcoholic fatty liver disease (NAFLD) is a common chronic
      liver disease ranging in severity from steatosis to cirrhosis. Type 2 diabetes
      mellitus is a cause of primary NAFLD. Thiazolidinediones have been shown to
      enhance insulin sensitivity, improve glycemic control in type 2 diabetes patients
      and to improve the histologic markers of nonalcoholic steatohepatitis. This study
      aims to determine the safety and effectiveness of rosiglitazone in inadequately
      controlled type 2 diabetes patients with NAFLD. METHODS: Taiwanese type 2
      diabetes patients with inadequate control on insulin secretagogues and metformin,
      with no history of significant alcohol ingestion, with mildly elevated serum
      aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and a
      diagnosis of fatty liver determined by ultrasonography were enrolled. Patients
      were treated for 24 weeks with rosiglitazone, 4-8 mg daily. Primary endpoints
      were change in AST and ALT levels from baseline and reduction in A1C < 6.5%.
      RESULTS: Out of a total of 68 patients, 60 (88.2%) completed the study treatment
      without serious adverse events. Treatment in two (2.9%) patients was discontinued
      due to elevated AST or ALT levels to more than three times the upper limit of
      normal, and noncompliance or loss of follow-up in six (8.8%) patients. Of the 60
      patients who completed the study treatment, mean fasting plasma glucose, A1C,
      fasting plasma insulin, mean ALT and homeostasis model assessment for insulin
      resistance were all significantly reduced. Normal AST and ALT levels were
      achieved and maintained for at least three consecutive measurements and through
      to the end of the study period in 20 (33.3%) patients. Weight increased by a mean
      of 2.6 +/- 2.4 kg (p < 0.001). CONCLUSION: Rosiglitazone was reasonably well
      tolerated in patients with inadequately controlled type 2 diabetes and NAFLD. One
      third of patients showed improved liver function after treatment.

PMID- 16959623
TI  - Penile tuberculosis associated with monoclonal gammopathy of undetermined
      significance.
AB  - Mycobacterium tuberculosis (TB) infection of the penis is a rare but serious
      problem. We report a case of penile TB in a 75-year-old man who presented with
      fever and dyspnea. No active lung lesions except pleural and pericardial effusion
      were found on chest X-ray. Monoclonal gammopathy of undetermined significance was
      diagnosed after serum and urine electrophoresis studies, and repeated bone marrow
      studies. Genital examination showed diffuse papulonecrotic skin ulcers involving
      the whole penile shaft, extending ventrally to the median raphe of the scrotum.
      Pus smear showed positive acid-fast stain, and culture yielded M. tuberculosis.
      Culture of pleural and pericardial effusion was also positive for M.
      tuberculosis. Anti-TB treatment was given with isoniazid, ethambutol, rifampin
      and pyrazinamide, and the cutaneous lesion was noted to be healed at follow-up 6
      months later. Although rare, the possibility of TB as a cause of genital ulcer
      should be kept in mind.

PMID- 16959624
TI  - Spontaneous Escherichia coli meningitis associated with hemophagocytic
      lymphohistiocytosis.
AB  - Spontaneous Escherichia coli meningitis has not been previously reported in
      association with hemophagocytic lymphohistiocytosis (HLH). A previously healthy
      72-year-old woman was admitted due to fever, nuchal rigidity, disturbed
      consciousness and splenomegaly. Anemia, thrombocytopenia and hyperferritinemia
      developed on the 8th day of hospitalization. Cultures of cerebrospinal fluid and
      blood grew E. coli. Abundant macrophages overwhelmed erythrocytes in the bone
      marrow aspirate, confirming the presence of hemophagocytosis. E. coli meningitis
      was managed with a 40-day course of antibiotic treatment. However, the severity
      of anemia and thrombocytopenia progressed despite intensive transfusion therapy.
      The patient died of HLH on the 60th day of hospitalization.

PMID- 16959625
TI  - Disseminated Streptococcus anginosus infection with empyema thoracis in a patient
      with sarcoma.
AB  - Streptococcus anginosus is a member of the normal flora of the oral cavity and a
      pathogen of thoracic infection. However, disseminated infection that was
      identified from different body fluids at the same time has never been reported.
      We report a 52-year-old man with advanced pulmonary sarcoma who developed
      neutropenia, bronchopleural fistula and thoracic empyema after chemotherapy.
      Viridans group Streptococcus was isolated from both empyema and urine, which was
      confirmed as S. anginosus according to the biochemical reaction profiles and 16S
      rRNA gene sequencing results. The patient recovered uneventfully after tube
      drainage and treatment with imipenem. Disseminated S. anginosus infection should
      be considered as a possible pathogen in immunocompromised patients with empyema
      and can be rapidly identified by 16S rRNA gene sequencing.

PMID- 16959626
TI  - Successful treatment of intractable hemothorax with recombinant factor VIIa in a
      nonhemophilic patient.
AB  - Recombinant factor VIIa (rFVIIa) was developed for the treatment of bleeding in
      hemophilic patients with inhibitors. It has also been used to stop bleeding in
      nonhemophilic patients who fail to respond to conventional treatment. We report a
      case of catastrophic hemothorax in which bleeding was stopped by administration
      of rFVIIa. A 68-year-old woman with chronic hepatitis C-related liver cirrhosis
      was admitted due to pneumonia and parapneumonic effusion. The patient developed
      hemothorax and hypovolemic shock after thoracentesis. Conventional therapies
      including tube thoracostomy and transarterial embolization failed to stop the
      life-threatening bleeding. The bleeding stopped after administration of rFVIIa
      100 microg/kg/BW at 2-hour intervals for a total of two doses on the 3rd day of
      hospitalization. Despite intensive care, however, the patient died due to
      nosocomial infection and multiple organ failure on the 12th day of
      hospitalization. Hemothorax in a nonhemophilic patient can be successfully
      treated with rFVIIa.

PMID- 16959627
TI  - Deficiency of the seventh component of complement in a Taiwanese boy.
AB  - Inherited complement deficiencies are rare, particularly those associated with
      late components of the complement cascade. We report a 5-year-4-month-old
      Taiwanese boy with systemic meningococcal infection who had undetectable CH50
      level of < 6 U/mL (normal, 32.6-39.8 U/mL). Levels of C3, C4, C5, C6 and C8 were
      normal, but C7 was undetectable (< 5.8 mg/dL; reference, 55-85 mg/dL). The
      patient's sister was also C7-deficient (CH50 < 6 U/mL, C7 < 5.8 mg/dL). His
      father's CH50 was 25.9 U/mL and C7 was 27.8 mg/dL. His mother's CH50 was 31.2
      U/mL and C7 was 22.7 mg/dL. His parents thus both had a partial complement
      deficiency, indicating an autosomal codominant inheritance pattern. Awareness of
      the possibility of late complement deficiency is important as they comprise a
      small percentage of patients who present with disseminated meningococcal disease
      or other serious infections caused by encapsulated organisms.

PMID- 16959628
TI  - Initial experience with ABO-incompatible live donor renal transplantation.
AB  - The serious shortage of cadaveric organs has prompted the development of ABO
      incompatible live donor renal transplantation. We report our experience of the
      initial two live donor ABO incompatible renal transplants at our hospital. The
      first patient was a 55-year-old type A female who received a kidney from her AB
      type husband. The second patient was a 27-year-old type O male who received renal
      transplantation from his type A father. Preconditioning immunosuppressive therapy
      in the two patients with tacrolimus, mycophenolate mofetil and methylprednisolone
      was started 7 days before transplantation. During the period of preconditioning,
      double filtration plasmapheresis (DFPP) was employed to remove anti-A and -B
      antibodies. Laparoscopic splenectomy and renal transplantation were performed
      after the anti-donor ABO antibodies were reduced to a titer of 1:4. Rituximab, a
      humanized monoclonal anti-CD20 antibody, was administered to the second patient
      due to a rebound in the anti-A antibody titer during the preconditioning period.
      Under a tacrolimus-based immunosuppressive regimen, both patients recovered very
      well without any evidence of rejection. Serum creatinine levels were 1.0 and 1.4
      mg/dL at 6 and 3 months after transplantation, respectively. These cases
      illustrate that with new immunosuppressive agents, DFPP and splenectomy, ABO
      incompatible renal transplantation can be successfully conducted in end-stage
      renal disease patients whose only available live donors are blood group
      incompatible.

PMID- 16959629
TI  - Aggregation, defence and warning signals: the evolutionary relationship.
AB  - In a seminal contribution, Fisher argued how distastefulness could incrementally
      evolve in a prey species that was distributed in family groups. Many defended
      prey species occur in aggregations, but did aggregation facilitate the evolution
      of defence as Fisher proposed or did the possession of a defence allow
      individuals to enjoy the benefits of group living? Contemporary theory suggests
      that it can work both ways: pre-existing defences can make the evolution of
      gregariousness easier, but gregariousness can also aid the evolution of defence
      and warning signals. Unfortunately, the key phylogenetic analyses to elucidate
      the ordering of events have been hampered by the relative rarity of gregarious
      species, which in itself indicates that aggregation is not a pre-requisite for
      defence. Like the underlying theory, experimental studies have not given a
      definitive answer to the relative timing of the evolution of defence and
      aggregation, except to demonstrate that both orderings are possible. Conspicuous
      signals are unlikely to have evolved in the absence of a defence and aggregated
      undefended prey are likely to be vulnerable to predation in the absence of
      satiation effects. It therefore seems most likely that defence generally preceded
      the evolution of both aggregation and signalling, but alternative routes may well
      be possible.

PMID- 16959630
TI  - Disruptive and cryptic coloration.

PMID- 16959631
TI  - Disruptive coloration provides camouflage independent of background matching.
AB  - Natural selection shapes the evolution of anti-predator defences, such as
      camouflage. It is currently contentious whether crypsis and disruptive coloration
      are alternative mechanisms of camouflage or whether they are interrelated anti
      predator defences. Disruptively coloured prey is characterized by highly
      contrasting patterns to conceal the body shape, whereas cryptic prey minimizes
      the contrasts to background. Determining bird predation of artificial moths, we
      found that moths which were dissimilar from the background but sported disruptive
      patterns on the edge of their wings survived better in heterogeneous habitats
      than did moths with the same patterns inside of the wings and better than cryptic
      moths. Despite lower contrasts to background, crypsis did not provide fitness
      benefits over disruptive coloration on the body outline. We conclude that
      disruptive coloration on the edge camouflages its bearer independent of
      background matching. We suggest that this result is explainable because
      disruptive coloration is effective by exploiting predators' cognitive mechanisms
      of prey recognition and not their sensory mechanisms of signal detection.
      Relative to disruptive patterns on the body outline, disruptive markings on the
      body interior are less effective. Camouflage owing to disruptive coloration on
      the body interior is background-specific and is as effective as crypsis in
      heterogeneous habitats. Hence, we hypothesize that two proximate mechanisms
      explain the diversity of visual anti-predator defences. First, disruptive
      coloration on the body outline provides camouflage independent of the background.
      Second, background matching and disruptive coloration on the body interior
      provide camouflage, but their protection is background-specific.

PMID- 16959632
TI  - Disruptive contrast in animal camouflage.
AB  - Camouflage typically involves colour patterns that match the background. However,
      it has been argued that concealment may be achieved by strategic use of
      apparently conspicuous markings. Recent evidence supports the theory that the
      presence of contrasting patterns placed peripherally on an animal's body
      (disruptive coloration) provides survival advantages. However, no study has
      tested a key prediction from the early literature that disruptive coloration is
      effective even when some colour patches do not match the background and have a
      high contrast with both the background and adjacent pattern elements (disruptive
      contrast). We test this counter-intuitive idea that conspicuous patterns might
      aid concealment, using artificial moth-like targets with pattern elements
      designed to match or mismatch the average luminance (lightness) of the trees on
      which they were placed. Disruptive coloration was less effective when some
      pattern elements did not match the background luminance. However, even non
      background-matching disruptive patterns reduced predation relative to equivalent
      non-disruptive patterns or to unpatterned controls. Therefore, concealment may
      still be achieved even when an animal possesses markings not found in the
      background. Disruptive coloration may allow animals to exploit backgrounds on
      which they are not perfectly matched, and to possess conspicuous markings while
      still retaining a degree of camouflage.

PMID- 16959633
TI  - The origin of modern crocodyliforms: new evidence from the Cretaceous of
      Australia.
AB  - While the crocodyliform lineage extends back over 200 million years (Myr) to the
      Late Triassic, modern forms-members of Eusuchia-do not appear until the
      Cretaceous. Eusuchia includes the crown group Crocodylia, which comprises
      Crocodyloidea, Alligatoroidea and Gavialoidea. Fossils of non-crocodylian
      eusuchians are currently rare and, in most instances, fragmentary. Consequently,
      the transition from Neosuchia to Crocodylia has been one of the most poorly
      understood areas of crocodyliform evolution. Here we describe a new crocodyliform
      from the mid-Cretaceous (98-95 Myr ago; Albian-Cenomanian) Winton Formation of
      Queensland, Australia, as the most primitive member of Eusuchia. The anatomical
      changes associated with the emergence of this taxon indicate a pivotal shift in
      the feeding and locomotor behaviour of crocodyliforms-a shift that may be linked
      to the subsequent rapid diversification of Eusuchia 20 Myr later during the Late
      Cretaceous and Early Tertiary. While Laurasia (in particular North America) is
      the most likely ancestral area for Crocodylia, the biogeographic events
      associated with the origin of Eusuchia are more complex. Although the fossil
      evidence is limited, it now seems likely that at least part of the early history
      of Eusuchia transpired in Gondwana.

PMID- 16959634
TI  - A mixed-mating strategy in a hermaphroditic vertebrate.
AB  - Mixed-mating systems, in which hermaphrodites can either self-fertilize or
      outcross, are common in many species of plants and invertebrates and have been
      informative models for studying the selective forces that can maintain both
      inbreeding and outbreeding in populations. Here, we document a remarkable
      instance of evolutionary convergence to an analogous mixed mating system by a
      vertebrate, the mangrove killifish (Kryptolebias marmoratus). In this
      androdioecious species, most individuals are simultaneous hermaphrodites that
      characteristically self-fertilize, resulting in local populations that consist of
      (nearly) homozygous lines. Most demes are also genetically diverse, an
      observation traditionally attributed to de novo mutation coupled with high levels
      of inter-site migration. However, data presented here, from a survey of 35
      microsatellite loci in Floridian populations, show that genotypic diversity also
      stems proximally from occasional outcross events that release 'explosions' of
      transient recombinant variation. The result is a local population genetic pattern
      (of extensive genotypic variety despite low but highly heterogeneous intra
      individual heterozygosities) that differs qualitatively from the genetic
      architectures known in any other vertebrate species. Advantages of a mixed-mating
      strategy in K. marmoratus probably relate to this fish's solitary lifestyle and
      its ability to colonize new habitats.

PMID- 16959635
TI  - Diluting the founder effect: cryptic invasions expand a marine invader's range.
AB  - Most invasion histories include an estimated arrival time, followed by range
      expansion. Yet, such linear progression may not tell the entire story. The
      European green crab (Carcinus maenas) was first recorded in the US in 1817,
      followed by an episodic expansion of range to the north. Its population has
      recently exploded in the Canadian Maritimes. Although it has been suggested that
      this northern expansion is the result of warming sea temperatures or cold-water
      adaptation, Canadian populations have higher genetic diversity than southern
      populations, indicating that multiple introductions have occurred in the
      Maritimes since the 1980s. These new genetic lineages, probably from the northern
      end of the green crab's native range in Europe, persist in areas that were once
      thought to be too cold for the original southern invasion front. It is well
      established that ballast water can contain a wide array of nonindigenous species.
      Ballast discharge can also deliver genetic variation on a level comparable to
      that of native populations. Such gene flow not only increases the likelihood of
      persistence of invasive species, but it can also rapidly expand the range of long
      established nonindigenous species.

PMID- 16959636
TI  - Sibling competition in a brood-tending leech.
AB  - Conflict among siblings over parental investment, particularly over parental
      feeding, is a feature of family life in many kinds of animals. In some bird
      species, the size of prey items provided to juveniles has been implicated as a
      cause of aggressive competition among sibling chicks, because prey size
      determines whether dominance allows monopolization of parental offerings. Our
      experiment was meant to test the generality of this factor in creating
      intrafamilial conflict. We investigated sibling competition in relation to prey
      size using the carnivorous, brood-tending leech Helobdella papillornata. We
      equalized the total amount of food available to H. papillornata broods, but
      varied the size of individual prey items. Competition, measured by disparity in
      body size at independence, was more intense in broods provisioned with small
      items than in broods receiving large items, but similar between broods receiving
      large items and broods fed ad libitum. These patterns suggest that the intensity
      of conflict did not depend only on the total food amount, but was enhanced by
      small prey size. Our results indicate that conflict over the provision of
      parental resources to offspring can have a similar basis across very dissimilar
      organisms.

PMID- 16959637
TI  - Key strategies for reducing spread of avian influenza among commercial poultry
      holdings: lessons for transmission to humans.
AB  - Recent avian flu epidemics (A/H5N1) in Southeast Asia and case reports from
      around the world have led to fears of a human pandemic. Control of these
      outbreaks in birds would probably lead to reduced transmission of the avian virus
      to humans. This study presents a mathematical model based on stochastic farm-to
      farm transmission that incorporates flock size and spatial contacts to evaluate
      the impact of control strategies. Fit to data from the recent epidemic in the
      Netherlands, we evaluate the efficacy of control strategies and forecast avian
      influenza dynamics. Our results identify high-risk areas of spread by mapping of
      the farm level reproductive number. Results suggest that an immediate
      depopulation of infected flocks following an accurate and quick diagnosis would
      have a greater impact than simply depopulating surrounding flocks. Understanding
      the relative importance of different control measures is essential for response
      planning.

PMID- 16959638
TI  - Gametic isolation in guppies (Poecilia reticulata).
AB  - Post-mating reproductive isolating mechanisms may be among the earliest
      reproductive barriers to emerge among incipient species. Trinidadian guppy,
      Poecilia reticulata, populations in the Caroni and Oropouche drainages in
      Northern Trinidad exhibit marked genetic divergence and provide an ideal system
      in which to search for these barriers. We inseminated virgin females with equal
      amounts of sperm from two males, a 'native' male from the female's own population
      and a 'foreign' male from the other drainage. Artificial insemination ensured
      that mating order and mate choice did not affect the outcome. Paternities were
      assigned to the resulting broods using microsatellite markers. As predicted,
      sperm from native males had precedence over foreign sperm. Moreover, this effect
      was symmetrical for both drainages. In contrast, we detected no native sperm
      precedence in controls, in which females received sperm from the same and another
      population within the same drainage. Our results show that gametic isolation can
      arise between geographically proximate, though genetically divergent, populations
      of a single species and highlight the potential role of this process in
      speciation.

PMID- 16959639
TI  - No evidence for presence of maternal mitochondrial DNA in the sperm of Mytilus
      galloprovincialis males.
AB  - Species of the mussel family Mytilidae have a special mitochondrial DNA (mtDNA)
      transmission system, known as doubly uniparental inheritance (DUI), which
      consists of a maternally inherited (F) and a paternally inherited (M)
      mitochondrial genome. Females are normally homoplasmic for the F genome and males
      are heteroplasmic mosaics, with their somatic tissues dominated by the maternal
      and their gonads dominated by the paternal genome. Several studies have indicated
      that the maternal genome may often be present in the male germ line. Here we
      report the results from the examination of mtDNA in pure sperm from more than 30
      males of Mytilus galloprovincialis. In all cases, except one, we detected only
      the M genome. In the sperm of one male, we detected a paternal genome with an F
      like primary sequence that was different from the sequence of the maternal genome
      in the animal's somatic tissues. We conclude that the male germ line is protected
      against invasion by the maternal genome. This is important because fidelity of
      gamete-specific transmission of the two mitochondrial genomes is a basic
      requirement for the stability of DUI.

PMID- 16959640
TI  - The impacts of different management strategies and environmental forcing in
      ecological communities.
AB  - Understanding the effects of population management on the community a target
      species belongs to is of key importance for successful management. It is known
      that the removal or extinction of a single species in a community may lead to
      extinctions of other community members. In our study, we assess the impacts of
      population management on competitive communities, studying the response of both
      locally stable and unstable communities of varying size (between four and 10
      species) to three different management strategies; harvesting of a target
      species, harvesting with non-targeted catch, and stocking of the target species.
      We also studied the consequences of selecting target species with different
      relative abundances, as well as the effects of varying environmental conditions.
      We show here how the effects of management in competitive communities extend far
      beyond the target population. A crucial role is played by the underlying
      stability properties of the community under management. In general, locally
      unstable communities are more vulnerable to perturbation through management.
      Furthermore, the community response is shown to be sensitive to the relative
      density of the target species. Of considerable interest is the result that even a
      small (2.5%) increase in the population size of the target species through
      stocking may lead to extinction of other community members. These results
      emphasize the importance of considering and understanding multi-species
      interactions in population management.

PMID- 16959641
TI  - Negative environmental perturbations may improve species persistence.
AB  - Among the factors proximally involved in the extinction of small isolated
      populations, genetic deterioration and temporal variation in environmental
      quality have been the subjects of intensive research in ecological and
      evolutionary sciences. However, previous theoretical studies and population
      viability assessments generally assumed a strict dichotomy between these two
      types of threat. Yet a number of empirical studies have recently suggested that
      the effects of genetic deterioration and environmental variation should not be
      considered independently, by demonstrating that the main effect of inbreeding
      depression lies with its tendency to exacerbate the deleterious consequences of
      environmental stress. Capitalizing on these results, I developed a stochastic
      model to examine the impact of random environmental perturbations on the
      persistence time of small isolated populations subject to inbreeding depression
      and mutation accumulation. The model assumes that spontaneous deleterious
      mutations have more severe effects when perturbations occur, which results in
      more efficient purging of the mutation load. Under this assumption, I find that
      negative perturbations may paradoxically improve middle- and long-term species
      persistence for realistic frequency of occurrence and severity distribution.

PMID- 16959642
TI  - Perceptual compression of space through position integration.
AB  - The mechanism of positional localization has recently been debated due to
      interest in the flash-lag effect, which occurs when a briefly flashed stationary
      stimulus is perceived to lag behind a spatially aligned moving stimulus. Here we
      report positional localization observed at motion offsets as well as at onsets.
      In the 'flash-lead' effect, a moving object is perceived to be behind a spatially
      concurrent stationary flash before the two disappear. With 'reverse-repmo',
      subjects mis-localize the final position of a moving bar in the direction
      opposite to the trajectory of motion. Finally, we demonstrate that simultaneous
      onset and offset effects lead to a perceived compression of visual space. By
      characterizing illusory effects observed at motion offsets as well as at onsets,
      we provide evidence that the perceived position of a moving object is the result
      of an averaging process over a short time period, weighted towards the most
      recent positions. Our account explains a variety of motion illusions, including
      the compression of moving shapes when viewed through apertures.

PMID- 16959643
TI  - Overconfidence in wargames: experimental evidence on expectations, aggression,
      gender and testosterone.
AB  - Overconfidence has long been noted by historians and political scientists as a
      major cause of war. However, the origins of such overconfidence, and sources of
      variation, remain poorly understood. Mounting empirical studies now show that
      mentally healthy people tend to exhibit psychological biases that encourage
      optimism, collectively known as 'positive illusions'. Positive illusions are
      thought to have been adaptive in our evolutionary past because they served to
      cope with adversity, harden resolve, or bluff opponents. Today, however, positive
      illusions may contribute to costly conflicts and wars. Testosterone has been
      proposed as a proximate mediator of positive illusions, given its role in
      promoting dominance and challenge behaviour, particularly in men. To date, no
      studies have attempted to link overconfidence, decisions about war, gender, and
      testosterone. Here we report that, in experimental wargames: (i) people are
      overconfident about their expectations of success; (ii) those who are more
      overconfident are more likely to attack; (iii) overconfidence and attacks are
      more pronounced among males than females; and (iv) testosterone is related to
      expectations of success, but not within gender, so its influence on
      overconfidence cannot be distinguished from any other gender specific factor.
      Overall, these results constitute the first empirical support of recent
      theoretical work linking overconfidence and war.

PMID- 16959644
TI  - Testing domains of danger in the selfish herd: sparrowhawks target widely spaced
      redshanks in flocks.
AB  - The main tenet of Hamilton's 'selfish herd theory' for the evolution of group
      living is that individual risk of being killed upon attack by a predator is
      greater when relatively far from conspecifics. Here we examine the role of
      spacing using video analysis of encounters between redshanks, Tringa totanus, in
      flocks on saltmarsh, and sparrowhawks, Accipiter nisus, surprise hunting from
      adjacent woodland. Targeted redshanks were 35% (approx. 5 body lengths) more
      widely spaced than their nearest non-targeted neighbours, controlling for
      proximity to the hawk. Although targeted redshanks were also twice as slow to
      escape, the effect dropped out of a model containing spacing, which alone
      accounted for twice as much variation as escape delay. Redshanks were more
      tightly spaced on the riskiest side of the flock, suggesting they attempted to
      compensate for the greater risk, while birds on the edges of flocks were more
      widely spaced than those in the centre. Our analysis controls for most of the
      confounding effects associated with the edge-centre comparisons that are normally
      used in similar studies and provides strong support for spacing-dependent
      differential predation risk in the wild. In general, we suggest that positive
      selection for tight spacing when prey are stationary is largely due to domains of
      danger, but that this also leads to positive selection when prey are mobile
      because of predator confusion.

PMID- 16959645
TI  - The role of survival for the evolution of female philopatry in a solitary
      forager, the grey mouse lemur (Microcebus murinus).
AB  - It is widely accepted that natal philopatry is a prerequisite for the evolution
      of sociality. The life-history hypothesis maintains that longevity of adults
      results in extended territory tenure and thus limits breeding vacancies for
      offspring, which makes natal philopatry more likely. Here, we tested the
      importance of longevity for natal philopatry in females of a basal primate, the
      grey mouse lemur (Microcebus murinus). This species is regarded as being solitary
      due to its foraging habits but while males disperse, female offspring in this
      species forgo dispersal and form long-term sleeping groups with their mothers. We
      tested whether high adult survival could be a cause for natal philopatry of
      female offspring. In addition, we assessed costs and benefits associated with
      space sharing between mothers and daughters and whether mothers actively increase
      survival of daughters by beqeauthal of territories, information transfer about
      resources or thermoregulation. Contrary to our predictions, adult females had low
      survival rates. Space sharing appeared to improve survival of both, mothers and
      daughters. This could be a result of information transfer about sleeping sites
      and thermoregulatory benefits. Our results cast doubt on the idea that longevity
      predisposes species for social traits and provide support for benefits of
      philopatry.

PMID- 16959646
TI  - Photosensitive neurogenic heart of the isopod crustacean Ligia exotica.
AB  - The heart of animals is regulated through the central nervous system in response
      to external sensory stimuli. We found, however, that the adult neurogenic heart
      of the isopod crustacean Ligia exotica has photosensitivity. The beat frequency
      of the isolated heart decreased in response to a light stimulus. Magnitude of the
      response was stimulus intensity dependent and the heartbeat frequency decreased
      to less than 80% of the dark value during illumination of the white light with an
      intensity of 6.0 mW cm-2. The spectral sensitivity curve of the heart
      photoresponse peaked at a wavelength around 520 nm. In response to 530 nm
      monochromatic light, the relationship between light intensity and response
      magnitude was linear and the threshold intensity was 7.26 x 1012 quanta cm-2 s-1.
      Bursting activity of the cardiac ganglion, which is located in the heart and acts
      as the cardiac pacemaker deceased in frequency in response to illumination by
      white light. This fact suggests that the heart photoresponse of L. exotica
      results from the photosensitivity of the cardiac ganglion neurons. The
      photoresponse of the heart therefore contributes to regulation of cardiac output
      in addition to other regulatory systems.

PMID- 16959648
TI  - Transgenerational priming of immunity: maternal exposure to a bacterial antigen
      enhances offspring humoral immunity.
AB  - Young vertebrates have limited capacity to synthesize antibodies and are
      dependent on the protection of maternally transmitted antibodies for humoral
      disease resistance early in life. However, mothers may enhance fitness by priming
      their offspring's immune systems to elevate disease resistance. Transgenerational
      induced defences have been documented in plants and invertebrates, but maternal
      priming of offspring immunity in vertebrates has been essentially neglected. To
      test the ability of mothers to stimulate the immune systems of offspring, we
      manipulated maternal and offspring antigen exposure in a wild population of
      birds, pied flycatchers (Ficedula hypoleuca). We show that immunization of the
      mother before egg laying apparently stimulates a transgenerational defence
      against pathogens by elevating endogenous offspring antibody production. If the
      disease environments encountered by mothers and offspring are similar, this
      transgenerational immune priming may allow young to better cope with the local
      pathogen fauna.

PMID- 16959647
TI  - Seasonal infectious disease epidemiology.
AB  - Seasonal change in the incidence of infectious diseases is a common phenomenon in
      both temperate and tropical climates. However, the mechanisms responsible for
      seasonal disease incidence, and the epidemiological consequences of seasonality,
      are poorly understood with rare exception. Standard epidemiological theory and
      concepts such as the basic reproductive number R0 no longer apply, and the
      implications for interventions that themselves may be periodic, such as pulse
      vaccination, have not been formally examined. This paper examines the causes and
      consequences of seasonality, and in so doing derives several new results
      concerning vaccination strategy and the interpretation of disease outbreak data.
      It begins with a brief review of published scientific studies in support of
      different causes of seasonality in infectious diseases of humans, identifying
      four principal mechanisms and their association with different routes of
      transmission. It then describes the consequences of seasonality for R0, disease
      outbreaks, endemic dynamics and persistence. Finally, a mathematical analysis of
      routine and pulse vaccination programmes for seasonal infections is presented.
      The synthesis of seasonal infectious disease epidemiology attempted by this paper
      highlights the need for further empirical and theoretical work.

PMID- 16959649
TI  - Early nutritional stress impairs development of a song-control brain region in
      both male and female juvenile song sparrows (Melospiza melodia) at the onset of
      song learning.
AB  - Birdsong is a sexually selected trait and is often viewed as an indicator of male
      quality. The developmental stress hypothesis proposes a model by which song could
      be an indicator; the time during early development, when birds learn complex
      songs and/or local variants of song, is of rapid development and nutritional
      stress. Birds that cope best with this stress may better learn to produce the
      most effective songs. The developmental stress hypothesis predicts that early
      food restriction should impair development of song-control brain regions at the
      onset of song learning. We examined the effect of food restriction on song
      control brain regions in fledgling (both sexes, 23-26 days old) song sparrows
      (Melospiza melodia). Food restriction selectively reduced HVC volume in both
      sexes. In addition, sex differences were evident in all three song-control
      regions. This study lends further support to a growing body of literature
      documenting a variety of behavioural, physiological and neural detriments in
      several songbird species resulting from early developmental stress.

PMID- 16959650
TI  - Evolutionary games and population dynamics: maintenance of cooperation in public
      goods games.
AB  - The emergence and abundance of cooperation in nature poses a tenacious and
      challenging puzzle to evolutionary biology. Cooperative behaviour seems to
      contradict Darwinian evolution because altruistic individuals increase the
      fitness of other members of the population at a cost to themselves. Thus, in the
      absence of supporting mechanisms, cooperation should decrease and vanish, as
      predicted by classical models for cooperation in evolutionary game theory, such
      as the Prisoner's Dilemma and public goods games. Traditional approaches to
      studying the problem of cooperation assume constant population sizes and thus
      neglect the ecology of the interacting individuals. Here, we incorporate
      ecological dynamics into evolutionary games and reveal a new mechanism for
      maintaining cooperation. In public goods games, cooperation can gain a foothold
      if the population density depends on the average population payoff. Decreasing
      population densities, due to defection leading to small payoffs, results in
      smaller interaction group sizes in which cooperation can be favoured. This
      feedback between ecological dynamics and game dynamics can generate stable
      coexistence of cooperators and defectors in public goods games. However, this
      mechanism fails for pairwise Prisoner's Dilemma interactions and the population
      is driven to extinction. Our model represents natural extension of replicator
      dynamics to populations of varying densities.

PMID- 16959651
TI  - Self-harm caused by an insect's innate immunity.
AB  - It has been a long-held assumption that the innate immune system of insects
      causes self-harm when used to combat an immune insult. We show empirically that
      this assumption is correct. Invertebrate innate immunity relies heavily on
      effector systems which, on activation, produce cytotoxins that kill pathogens.
      Reliance on these robust, fast-acting, generic killing mechanisms ensures a
      potent and rapid response to pathogen invasion, but has the potential
      disadvantage of causing self-damage. We show that the innate immune response
      against an immune insult produces measurable phenotypic and functional damage to
      self-tissue in the beetle Tenebrio molitor. This type of self-harm
      (autoreactivity) and the life-history implications that arise from it are
      important to understand evolutionary phenomena such as the dynamics between hosts
      and parasites as well as the nature of immune system costs.

PMID- 16959652
TI  - Compensation for research-related injuries. Ethical and legal issues.

PMID- 16959653
TI  - Implied preemption of state tort law claims against prescription drug
      manufacturers based upon FDA approval.

PMID- 16959654
TI  - Accommodations for the disabled during administration of the MCAT. Individual
      state interests versus national uniformity.

PMID- 16959655
TI  - "The mercury's rising!" Can national health group intervention protect the public
      health from EPA'S Clean Air Mercury Rule?

PMID- 16959656
TI  - An American Muslim's right to die. Incorporating Islamic law into the debate.

PMID- 16959659
TI  - Psychosocial variables of sexual satisfaction in Chile.
AB  - This study analyzed psychosocial variables of sexual satisfaction in Chile using
      data from the COSECON survey. Participants were 5,407 subjects (2,244 min and
      3,163 women, aged 18-69 years). We used a cross-sectional questionnaire with a
      national probability sample. Data were collected using a thorough sexual behavior
      questionnaire consisting of 190 face-to-face questions and 24 self-reported
      questions. A single item included in the COSECON questionnaire assessed sexual
      satisfaction. Results showed that high education level, marital status, and high
      socioeconomic levels were associated with sexual satisfaction in women but not in
      men. The results also showed important gender differences and sustain the idea
      that sexuality changes may be more present in middle and high social classes. The
      proximal variables typically used for measuring sexual satisfaction, such as the
      frequency of sexual intercourse and orgasm, showed a positive but smaller
      association with sexual satisfaction. Other important variables related to sexual
      satisfaction were being in love with the partner and having a steady partner. The
      results confirmed previous findings and are discussed in the frame of approaches
      like the exchange, equity, and sexual scripts theories.

PMID- 16959660
TI  - The enhancement of female sexual function with ArginMax, a nutritional
      supplement, among women differing in menopausal status.
AB  - We conducted a double-blind, placebo-controlled study to determine the role of
      dietary supplementation on sexual function in women of differing menopausal
      status. One hundred eight (108) women, age 22-73 years, who reported a lack of
      sexual desire, enrolled as participants. Of these, 55 received ArginMax for women
      and 53 received placebo. ArginMax for women contains L-arginine, ginseng, ginkgo,
      damiana, multivitamins, and minerals. The 108 women, given definitions, self
      reported as 59 premenopausal (PRE); 20 perimenopausal (PERI), and 29
      postmenopausal (POST). After 4 weeks, PRE women on ArginMax primarily reported
      significant improvement in level of sexual desire (72%; p = 0.03) and
      satisfaction with overall sex life (68%; p = 0.007), compared with placebo group,
      according to the Female Sexual Function Index (FSFI; Kaplan et al., 1999) scales.
      Frequency of sexual desire (60%; p = 0.05) and frequency of intercourse (56% p =
      0.01) also increased among the PRE women. In contrast, among PERI women, primary
      improvements were reported for frequency of intercourse (86%; p = 0.002),
      satisfaction with sexual relationship (79%; p = 0.03), and vaginal dryness (64%;
      p = 0.03) compared with placebo group. POST women primarily showed an increased
      in level of sexual desire, with 51% showing improvement, compared with only 8% in
      the placebo group (p = 0.008). Nutritional intervention plays an important role
      in women's sexual health, but issues and areas of greatest improvement differ
      among women of different menopausal states. The largest number of attribute
      improvements were seen in PRE and PERI women, although attribute types vary among
      these groups. Level of desire was shown to increase significantly in POST women.
      Since ArginMax for women has been shown to exhibit no estrogen activity, it may
      be desirable alternative to hormone therapy for sexual concerns.

PMID- 16959661
TI  - Management and outcome of primary vaginismus.
AB  - Our objective was to access the success rate, and the factors affecting it, of
      treatment based on Masters and Johnson's sex therapy. For this prospective study,
      we enrolled 120 couples with unconsummated coitus due to vaginismus. We made a
      clinical diagnosis after taking a detailed history taking and conducting a
      clinical examination. Participants completed a questionnaire regarding
      characteristics of vaginismus after participating in a face-to-face interview.
      Both of these were done prior to treatment, after 3 months, and after 12 months.
      We provided sex therapy based on Masters and Johnson's method. Treatment results
      were then analyzed. After therapy, 93.3% of vaginismic women were successfully
      penetrated, and 83.3% had regular intercourse with orgasm. The abilities to reach
      orgasm and sexual desire were not different than that among normal women. There
      was a correlation between duration of unconsummation and success rate and also
      between severity of vaginismus, treatment sessions, and success rate. Because of
      our high success rate, we encourage vaginismic women and their partners to accept
      aggressive management.

PMID- 16959662
TI  - Restoration of satisfying sex for a castrated cancer patient with complete
      impotence: a case study.
AB  - We present a first-hand account of a fully impotent, testosterone-suppressed
      prostate cancer patient who has satisfying, multiorgasmic sex using a strap-on
      dildo. We use his narrative to examine dildos as an alternative to erectile
      dysfunction treatments for men, such as this patient, who find selective
      inhibitors of PDE-5 ineffective and surgical intervention unacceptable. We
      explore what conditions allowed this man to progress from suspicious distrust of
      the dildo to full acceptance. In terms of making a dildo acceptable to other
      patients, we contrast offering it to them as a penile prosthesis in a formal
      medical setting versus treating it as a toy in fantasy sex play. Last, we present
      a neurobiological hypothesis involving sensory integration to help explain why
      sex with the strap-on dildo can be satisfying to a male.

PMID- 16959663
TI  - Treating erectile dysfunction through electronic consultation: a pilot study.
AB  - We investigated a group of men suffering from electric dysfunction (ED) who
      visited the website www.erectie.info and who had received consultation through
      the Internet (n = 219). We measured the treatment's effectiveness using the 5
      item version of the International Index of Erectile Function (IIEF-5; Rosen et
      al., 1996; Rosen, Cappelleri, Smith, Lipsky, & Pena, 1999) and a global
      assessment question (GAQ). We investigated the motives and characteristics of the
      users of electronics consultation using a questionnaire. After a few months, the
      consultation group showed a considerably higher IIEF-5 score compared with their
      baseline score. Eighty-one percent replied in the affirmative to the GAQ. E
      consultation is likely to be effective when treating ED, especially among men who
      find the medium convenient and for men who experience much embarrassment.

PMID- 16959664
TI  - Low relationship satisfaction and high partner involvement predict sexual
      problems of women with fibromyalgia.
AB  - To examine the predictive potential of relationship variables on sexual
      functioning in women with fibromyalgia, we instructed 63 women (age 21-54 years)
      to fill out several questionnaires. Low relationship satisfaction was the
      strongest and most-frequent predictor of problematic sexual functioning. In
      addition, more fatigue and--only after taking account of relationship
      satisfaction--more active engagement (i.e., involvement) of the spouse were
      associated with reduced sexual functioning and satisfaction. Our study suggests
      that for women with fibromyalgia, relationship satisfaction is good for sexual
      functioning. Although having an involved spouse is good for the relationship, it
      may be bad for sexual functioning.

PMID- 16959668
TI  - Community-based tai chi and its effect on injurious falls, balance, gait, and
      fear of falling in older people.
AB  - BACKGROUND AND PURPOSE: It is important to determine the effect of adherence to a
      tai chi program on falls and related functional outcomes in older people. This
      study examined the effect of a community-based tai chi program on injurious
      falls, balance, gait, and fear of falling among people aged 65 years and older in
      Taiwan. SUBJECTS AND METHODS: In 6 rural villages in Taichung County, 1,200
      subjects participated in the initial assessment. During a 1-year intervention
      period, all study villages were provided with education on fall prevention. Two
      villages had been provided tai chi exercise (n=472 participants or "tai chi
      villagers"), and 4 villages served as control villages (n=728 participants or
      "control villagers"). Injurious falls were ascertained by telephone interviews
      every 3 months over a 2-year study period; additionally, balance, gait, and fear
      of falling were assessed in 2 follow-up assessments. RESULTS: Eighty-eight
      subjects, 83 from the tai chi villages and 5 from the control villages,
      participated and practiced in the tai chi program (the group labeled "tai chi
      practitioners"). After the tai chi program, injurious falls among the control
      villagers significantly declined by 44% (adjusted rate ratio [RR]=0.56; 95%
      confidence interval [CI]=0.36-0.92). Compared with the results for the control
      villagers, the decline was 31% greater (RR=0.69; 95% CI=0.30-1.56) among the tai
      chi villagers and 50% greater (RR=0.5; 95% CI=0.11-2.17) among the tai chi
      practitioners; the results did not reach statistical significance. Furthermore,
      compared with the scores for the control villagers, the scores for the tai chi
      practitioners increased by 1.8 points (95% CI=0.2-3.4) on the Tinetti Balance
      Scale and increased by 0.9 point (95% CI=0.1-1.8) on the Tinetti Gait Scale. No
      significant changes in the fear of falling were detected among the tai chi
      practitioners, tai chi villagers, and control villagers. DISCUSSION AND
      CONCLUSION: Tai chi can prevent a decline in functional balance and gait among
      older people. However, the reduction in injurious falls attained with tai chi did
      not reach statistical significance; the statistical inefficiency may have
      resulted partly from the large decline in injurious falls in control villagers.
      Finally, the unexpected effect of educational intervention on reducing injurious
      falls in different settings needs to be further examined.

PMID- 16959669
TI  - Identification of intervention categories for physical therapy, based on the
      international classification of functioning, disability and health: a Delphi
      exercise.
AB  - BACKGROUND AND PURPOSE: Disability or limitations in human functioning are
      universal experiences that concern all people. Physical therapists aim to improve
      functioning and prevent disability. With the approval of the new International
      Classification of Functioning, Disability and Health (ICF), we can now rely on a
      globally recognized framework and classification to be used in different health
      care situations by all health care professionals in multidisciplinary teams. The
      objective of this study was to identify ICF categories that describe the most
      relevant and common patient problems managed by physical therapists in acute,
      rehabilitation, and community health care situations taking into account 3 major
      groups of health conditions: musculoskeletal, neurological, and internal.
      SUBJECTS: The subjects were physical therapists who were identified as possible
      participants by the heads of physical therapy departments who were members of the
      Swiss Association of Physical Therapy Department Heads or who were recruited from
      the membership of the Swiss Association of Physiotherapy. METHODS: A consensus
      building, 3-round, electronic-mail survey with 9 groups of physical therapists
      was conducted using the Delphi technique. RESULTS: Two hundred sixty-three
      physical therapists participated in at least one round of the Delphi exercise.
      They had consensus levels of 80% or higher for categories in all ICF components
      (Body Functions, Body Structures, Activities and Participation, and Environmental
      Factors 1 and 2). DISCUSSION AND CONCLUSION: This study is a first step toward
      identifying a list of intervention categories relevant for physical therapy
      according to the ICF. The ICF, designed as a common language for
      multidisciplinary use, is also a very helpful framework for defining the core
      competence for the physical therapy profession.

PMID- 16959670
TI  - Are teaching principles associated with improved motor performance in children
      with developmental coordination disorder? A pilot study.
AB  - BACKGROUND AND PURPOSE: Physical therapists' teaching skills often are
      disregarded in research studies. We examined whether the use of different
      teaching principles during neuromotor task training was associated with treatment
      effects. SUBJECTS: Nineteen children (mean age=7 years 5 months, range=5-10
      years) who had developmental coordination disorder and who performed below the
      15th percentile on the age-related Movement Assessment Battery for Children (M
      ABC) and 11 physical therapists participated in the study. METHODS: One
      intervention session for each child was videotaped. The frequency of the use of
      principles included in the motor teaching principles taxonomy (Niemeijer et al,
      2003) was correlated with changes in motor performance on the M-ABC and the
      second edition of the Test of Gross Motor Development. RESULTS: Providing clues
      on how to perform a task, asking children about a task, and explaining why a
      movement should be executed in a certain way were related to better movement
      performance. DISCUSSION AND CONCLUSION: Teaching principles may be associated
      with success in therapeutic situations.

PMID- 16959671
TI  - Measurement of muscle thickness as quantitative muscle evaluation for adults with
      severe cerebral palsy.
AB  - BACKGROUND AND PURPOSE: The muscle strength of people with severe cerebral palsy
      (CP) is difficult to quantify because of cognitive and selective motor control
      problems. However, if muscle strength is related to muscle atrophy caused by
      activity limitation, quantitative morphological analysis such as analysis of
      muscle thickness (MTH), measured by ultrasound imaging, may be used to examine
      the muscle condition in daily use. The primary purpose of this investigation was
      to clarify the difference in MTH of several muscles by the motor functions used
      in daily activity in adults with CP with different levels of severity of
      involvement. The secondary purpose was to examine whether MTH is associated with
      age, body characteristics, and muscle spasticity. SUBJECTS: Data were collected
      from a convenience sample of 25 adults with severe CP. METHODS: The MTH of the
      biceps brachii (BB), quadriceps femoris (QF), triceps surae (TS), and longissimus
      (LO) muscles was measured with an ultrasound imaging device. The severity of the
      condition was classified with the Gross Motor Function Classification System
      (GMFCS), and functional status in sitting and standing was evaluated with a
      questionnaire administered to the staff assisting in the care of the subjects.
      Muscle spasticity was assessed with the Modified Ashworth Scale (MAS). RESULTS:
      The MTH of the QF, LO, and TS showed significant differences according to the
      GMFCS level, and the MTH of the QF and LO differed significantly depending on
      functional status during activities of daily living. Age and body mass index
      showed no significant correlation with the MTH of any muscle. Body weight was
      correlated with the MTH of the BB and LO. The girth of the extremity was
      correlated only with the MTH of the BB. There was no relationship between MTH and
      MAS scores. DISCUSSION AND CONCLUSION: These results suggest that the MTH of the
      QF and LO differed significantly depending on the subjects' motor function during
      daily activity. The measurement of MTH may be an alternative method of
      quantitative muscle evaluation for people with severe CP for whom direct
      measurement of muscle strength is difficult.

PMID- 16959672
TI  - Pain, fatigue, and intensity of practice in people with stroke who are receiving
      constraint-induced movement therapy.
AB  - BACKGROUND AND PURPOSE: There is little available information about changes in
      pain and fatigue status among people receiving constraint-induced movement
      therapy (CI therapy). This study examined such changes. SUBJECTS: All
      participants were a subset of individuals with stroke enrolled in the Extremity
      Constraint-Induced Therapy Evaluation (EXCITE) trial and received 2 weeks of CI
      therapy either 3 to 9 months after stroke (subacute therapy group, n=18) or 1
      year later (chronic therapy group, n=14). METHODS: Pain, fatigue, and intensity
      of therapy were evaluated. The Wolf Motor Function Test (WMFT) and the pain scale
      of the Fugl-Meyer Assessment for the upper extremity were administered before and
      after training. Single-item measures for pain and fatigue were administered twice
      daily during therapy. RESULTS: All participants reported low mean pain (X=2.0,
      SD=0.93) and fatigue (X=2.7, SD=1.23) scores. Generally, differences between the
      subacute and the chronic therapy groups for pain, fatigue, intensity, and WMFT
      change scores were nonsignificant. DISCUSSION AND CONCLUSION: For selected
      patients with stroke, the intensive practice associated with CI therapy may be
      administered without exacerbation of pain or fatigue, even early during the
      recovery process.

PMID- 16959673
TI  - Impact of continuing education interventions on clinical outcomes of patients
      with neck pain who received physical therapy.
AB  - BACKGROUND AND PURPOSE: Physical therapists frequently attend continuing
      education courses with the goal of providing better care, yet the effectiveness
      of continuing education for improving outcomes has not been examined. SUBJECTS:
      Data were obtained for all eligible patients (n=1,365; mean age=42.1 years,
      SD=14.0 years; 69.9% female) with a chief complaint of neck pain who were treated
      in 13 physical therapy clinics over a 24-month period. Disability data (Neck
      Disability Index scores) from the initial and final therapy sessions were
      recorded from clinical databases. METHODS: Thirty-four of 57 physical therapists
      employed within the 13 clinics attended a 2-day continuing education course.
      Eleven of the 34 attendees also participated in an ongoing clinical improvement
      project for patients with neck pain. Clinical outcomes were compared in the pre-
      and post-course periods for therapists attending or not attending the course, and
      for therapists participating or not participating in the ongoing project.
      RESULTS: There were no differences in clinical outcomes based on attendance at
      the continuing education course. There was an interaction between time and
      participation in the ongoing project, such that participants achieved greater
      change in disability after the course. The percentage of patients achieving at
      least the minimum detectable amount of change in disability with treatment
      increased significantly for participants after the course. DISCUSSION AND
      CONCLUSION: Attendance at a 2-day continuing education course was not associated
      with improvement in clinical outcomes, but participation in an ongoing
      improvement project did result in greater clinical improvement for patients with
      neck pain. Further investigation of educational methods to improve clinical
      outcomes is needed. These results suggest that traditional continuing education
      formats may not be effective for improving patient care.

PMID- 16959674
TI  - Allometric analysis of physical performance measures in older adults.
AB  - BACKGROUND AND PURPOSE: Body mass is a confounding variable in human performance,
      and adjusting physical performance measures for body mass differences would allow
      meaningful individual and group comparisons. The purpose of this study was to
      allometrically determine the relationship between body mass and handgrip and
      ankle dorsiflexor performance on the Timed "Up & Go" Test (TUGT). SUBJECTS: One
      hundred thirty-one subjects (33 male and 98 female) participated. METHODS: All
      physical performance measures were adjusted for the influence of body mass, sex,
      and age using an allometric scaling procedure. RESULTS: For handgrip force, the
      body mass exponent from allometric analysis was 0.63. For the TUGT, the body mass
      exponent was 0.073. For ankle dorsiflexor force and torque, the body mass
      exponents were 0.82 and 0.91, respectively. DISCUSSION AND CONCLUSION: The body
      mass exponents for handgrip force and the TUGT agree with previous clinical data
      and theoretical expectations. Studies investigating normalized handgrip force in
      older adults should consider an allometric scaling approach.

PMID- 16959675
TI  - Effects of physical training on functional status in patients with prolonged
      mechanical ventilation.
AB  - BACKGROUND AND PURPOSE: Patients requiring prolonged mechanical ventilation (PMV)
      are frequently deconditioned because of respiratory failure precipitated by the
      underlying disease, the adverse effects of medications, and a period of prolonged
      immobilization. The effects of 6 weeks of physical training on the strength of
      respiratory and limb muscles, on ventilator-free time, and on functional status
      in patients requiring PMV were examined. SUBJECTS: Thirty-nine patients with PMV
      were initially enrolled in the study and were assigned to either a treatment
      group (n=20) or a control group (n=19). Three subjects in the treatment group and
      4 subjects in the control group died during the 6-week intervention period and
      thus their data were excluded from the final analysis. METHODS: Subjects in the
      treatment group received physical training 5 days a week for 6 weeks. Strength of
      respiratory and limb muscles, ventilator-free time, and functional status, which
      was measured by the Barthel Index of Activities of Daily Living (BI) and
      Functional Independence Measure (FIM), were examined at baseline and at the third
      and sixth weeks of the study period. RESULTS: Respiratory and limb muscle
      strength improved significantly at the third and sixth weeks in the treatment
      group compared with baseline measurements. Total BI and FIM scores increased
      significantly in the treatment group and remained unchanged in the control group.
      Effect sizes of the BI and FIM scores were 2.02 and 1.93, respectively, at the
      sixth week. DISCUSSION AND CONCLUSION: The results show that a 6-week physical
      training program may improve limb muscle strength and ventilator-free time and
      thus improve functional outcomes in patients requiring PMV.

PMID- 16959676
TI  - Gait training of patients after stroke using an electromechanical gait trainer
      combined with simultaneous functional electrical stimulation.
AB  - BACKGROUND AND PURPOSE: This case report describes the implementation of gait
      training intervention that used an electromechanical gait trainer with
      simultaneous functional electrical stimulation (FES) for 2 patients with acute
      ischemic stroke. CASE DESCRIPTION: Two individuals with post-stroke hemiplegia of
      less than 6 weeks' duration participated in a 4-week gait training program as an
      adjunct to physical therapy received at a hospital. After the 4-week
      intervention, both patients were discharged from the hospital, and they returned
      after 6 months for a follow-up evaluation. OUTCOMES: By the end of the 4-week
      intervention, both patients had shown improvements in scores on the Barthel
      Index, Berg Balance Scale, Functional Ambulation Categories Scale, 5-m timed
      walking test, and Motricity Index. In the 6-month follow-up evaluation, both
      patients continued to have improvements in all outcome measures. DISCUSSION: This
      case report shows that, following the use of an electromechanical gait trainer
      simultaneously with FES, patients after acute stroke had improvements in gait
      performance, functional activities, balance, and motor control in the long term.

PMID- 16959677
TI  - A collaborative model of service delivery for children with movement disorders: a
      framework for evidence-based decision making.
AB  - Models of physical therapist service delivery provide a framework for integration
      of knowledge, research, and assumptions in a clinically relevant context that
      facilitates evidence-based decision making. In this perspective, a collaborative
      model of service delivery for children with movement disorders is presented. The
      focus is on services that address child and family priorities and preferences in
      settings where children live, learn, and play. The International Classification
      of Functioning, Disability and Health (ICF) is applied to identify relationships
      among the components of functioning, environmental, and personal factors that are
      important for the plan of care and achievement of outcomes. An assumption of the
      model is that physical therapists use multiple types of evidence to guide
      decision making. Application of the model and how child and family priorities
      change over time are illustrated through a longitudinal case report of a child
      with cerebral palsy.

PMID- 16959678
TI  - Generic and commercial low molecular weight heparins.

PMID- 16959679
TI  - Thromboembolism in cancer patients: pathogenesis and treatment.
AB  - In this review we summarize the causes of cancer related thrombosis as well as
      modern treatment approaches. Malignancy as a risk factor for thromboembolism is
      becoming increasingly recognized by clinicians caring for these patients. The
      probability of thrombosis occurring in an individual patient is dependent on
      several factors, including accompanying medical problems, the type of cancer, the
      clinical stage, performance status, and the treatment modalities employed.
      Thrombophilia with a history of thromboembolism is important as well. The overall
      risk of thrombosis is sevenfold that of noncancer patients. Though much has been
      learned about the pathogenesis of cancer-related thrombosis, we are in fact just
      beginning to understand the cross-talk between cancer cells and their related
      microenvironment, and such investigations are likely to increase our knowledge of
      cancer-related thrombosis mechanisms. Research in these areas may also suggest
      new strategies for cancer prevention, metastasis suppression, and new treatments.
      Drugs used in cancer therapy are increasingly recognized to directly contribute
      to the thrombotic tendency. Few studies provide data on the optimal management of
      cancer patients with thrombosis. It has been learned that retreating with the
      same drug can be very hazardous. In general the approach to prevention of
      thrombosis is the same as for noncancer patients, recognizing that specific
      cancer types and stage can place a patient in a high-risk category. Initial
      coumadin therapy fails in a significant number of patients with cancer.
      Recognition of the cancer patients at highest risk for coumadin failure is
      challenging. Low-molecular-weight heparins appear to be more effective in such
      situations where coumadin is likely to fail or has failed, but these drugs are
      thought to be costlier. Newer agents such as Factor Xa inhibitors and TF
      inhibitors are currently under investigation and may be found useful in the
      management of cancer-related thrombosis.

PMID- 16959680
TI  - Product individuality of commercially available low-molecular-weight heparins and
      their generic versions: therapeutic implications.
AB  - The currently available brand-name low-molecular-weight heparins (LMWHs) in the
      United States include dalteparin (Pfizer), enoxaparin (Aventis), and tinzaparin
      (Pharmion). Other products available, in Europe, include certoparin (Novartis),
      reviparin (Abbott), nadroparin (GlaxoSmithkline), and parnaparin (Alpha
      Wasserman). Each of these LMWHs has a characteristic molecular weight profile and
      biological activity in terms of an anti-FXa and anti-FIIa potency. The mean
      molecular weight of these drugs ranges from 4.0 kDa to 7.0 kDa and the anti
      FXa:anti-FIIa ratio ranges from 1.5 to 3.5. These agents may also be
      characterized by the presence of specific chemical end groups such as 2-O-sulfo-4
      enepyranosuronic acid at the nonreducing terminus (enoxaparin) or 2,5-anhydro-D
      mannose at the reducing terminus (dalteparin). Further, the component
      oligosaccharide chains exhibit product-specific distribution profiles. It is now
      widely accepted that individual LMWHs are chemically unique agents and cannot be
      interchanged therapeutically. Each commercial LMWH has been individually
      developed for specific clinical indications, which are dose and product
      dependent. Recently, several generic LMWHs have become available in India
      (Cutenox and Markaparin) and South America (dilutol, clenox, dripanina), and
      three companies have filed for regulatory approval of a generic version of
      enoxaparin in the United States. As the primary aim of a generic drug is to
      reduce cost without compromising patient care, a generic drug is required to be
      chemically and biologically equivalent to the pioneer drug. Because LMWHs
      represent complex natural mucopolysaccharide drugs that have undergone chemical
      and enzymatic modifications, physicochemical and biological information in
      addition to molecular weight and anti-FXa:anti-FIIa ratio should be used to
      determine generic equivalency to the branded drug. We have utilized a previously
      reported approach to systematically compare three generic versions of enoxaparin
      obtained from India and Brazil with the branded enoxaparin (Lovenox) available in
      the United States. Testing included molecular and structural profiling,
      evaluation in clot-based and amidolytic anti-FXa and anti-FIIa assays, and
      heparinase-I digestion profiles. While the molecular profiles (4.8 +/- 1.8 kD)
      and anticoagulant potencies as determined by activated partial thromboplastin
      time (APTT) were comparable for all four agents, the generic products showed
      variations in the thrombin time (TT) and Heptest assays. Two generic and the
      branded enoxaparin were readily digested by heparinase-I, losing most of their
      anticoagulant activity, but one generic product resisted digestion. This may have
      been due to a unique structural feature in this product. These studies show that,
      while generic LMWHs may exhibit acceptable molecular weight and anti-FXa
      profiles, they can exhibit assay-based differences and digestion profiles.
      Testing in animal models to determine safety, efficacy, and pharmacodynamic
      parameters may be important to verify equivalence. In order to assure that the
      generic LMWHs are equivalent to branded LMWHs such that equivalent clinical
      results are obtained, there is a need to develop clear stepwise guidelines that
      will establish equivalency in terms of physical, chemical, biochemical,
      pharmacokinetic, and pharmacodynamic properties for these anticoagulant drugs.

PMID- 16959681
TI  - Characterization of recessive severe type 1 and 3 von Willebrand Disease (VWD),
      asymptomatic heterozygous carriers versus bloodgroup O-related von Willebrand
      factor deficiency, and dominant type 1 VWD.
AB  - Recessive type 3 von Willebrand disease (VWD) is caused by homozygosity or double
      heterozygosity for two non-sense mutations (null alleles). Type 3 VWD is easy to
      diagnose by the combination of a strongly prolonged bleeding time (BT), absence
      of ristocetine-induced platelet aggregation (RIPA), absence of von Willebrand
      factor (VWF) protein, and prolonged activated partial thromboplastin time (aPTT)
      due to factor VIII:coagulant (FVIII:C) deficiency. VWD type 3 is associated with
      a pronounced tendency to mucocutaneous and musculoskeletal bleedings since early
      childhood. Carriers of one null allele are usually asymptomatic at VWF levels of
      50% of normal. Recessive severe type 1 VWD is caused by homozygosity or double
      heterozygosity for a missense mutation. Recessive type 1 VWD differs from type 3
      VWD by the presence of detectable von Willebrand factor: antigen VWF:Ag and
      FVIII:C levels between 0.09 and 0.40 U/mL. Patients with recessive type 1 VWD
      show an abnormal VWF multimeric pattern in plasma and/or platelets consistent
      with severe type 2 VWD. Carriers of a missense mutation may have mild bleeding
      and mild VWF deficiency and can be diagnosed by a double VWF peak on cross
      immunoelectrophoresis (CIE). There will be cases of mild and moderate recessive
      type 1 VWD due to double heterozygosity of two missense mutations, or with the
      combination of one missense mutation with a non-sense or bloodgroup O. Mild
      deficiency of VWF in the range of 0.20 to 0.60 U/mL, with normal ratios of von
      Willebrand factor: ristocetine cofactor/antigen VWF:RCo/Ag and VWF:collagen
      binding/antigen (VWF:CB/Ag), normal VWF multimers, and a completely normal
      response to desmopressin acetate (DDAVP) with VWF level rising from below to
      above 1.00 U/mL are very likely cases of so-called pseudo-VWF deficiency in
      individuals with normal VWF protein and gene. Autosomal dominant type 1 VWD
      variants are in fact type 2 variants caused by a heterozygous missense mutation
      in the VWF gene that produces a mutant VWF protein that has a dominant effect on
      normal VWF protein produced by the normal VWF allele with regard to the
      synthesis, processing, storage, secretion, and/or proteolysis of VWF in
      endothelial cells. A DDAVP challenge test clearly differentiates between dominant
      type 1 VWD phenotype and dominant type 2 M VWD.

PMID- 16959682
TI  - Diagnosis and follow-up of thrombotic thrombocytopenic purpura by means of von
      Willebrand factor collagen binding assay.
AB  - Thrombotic thrombocytopenic purpura (TTP) is characterized by intravascular
      thrombosis leading to consumption of large or unusually large von Willebrand
      factor (VWF) multimers. The usefulness of VWF collagen binding (VWF:CB) assay was
      assessed in detecting the decrease/absence of large VWF multimers or the presence
      of abnormally large forms in patients with TTP. Nine patients with TTP were
      studied during the acute phase of the disorder and the absence of large VWF
      multimers was demonstrated by means of the VWF:CB assay. These findings were
      confirmed by VWF multimer pattern analysis; VWF:CB deficiency appeared to
      correlate with abnormalities in large VWF multimers. The diagnostic potency of
      VWF:CB was especially evident when the values were expressed as VWF:CB/VWF:Ag
      ratio. VWF:CB was also used during the follow-up of the disorder to document
      improvement or restoration of large VWF multimers. VWF:CB was able to detect the
      absence or decrease of large VWF multimers better than VWF ristocetin cofactor
      (VWF:RCo); in fact, VWF:CB was defective when large VWF multimers persisted to be
      decreased, in contrast with what observed with VWF:RCo. In conclusion, VWF:CB is
      a simple test that appears to be useful, together with clinical symptoms and
      reduced platelet count, for the diagnosis and follow-up of TTP.

PMID- 16959683
TI  - Determination of von Willebrand factor activity: evaluation of the HaemosIL assay
      in comparison with established procedures.
AB  - Determination of von Willebrand factor activity is required for diagnosis and
      classification of von Willebrand disease. In addition, von Willebrand factor
      activity can be of prognostic relevance in several clinical entities including
      thromboembolic and cardiovascular disorders in which elevated activity correlates
      with a poor prognosis. The HaemosIL assay (Instrumentation Laboratory GmbH,
      Munich, Germany) provides a new fully automated procedure for determination of
      von Willebrand factor activity. This assay measures binding of the von Willebrand
      factor to GP Ibalpha of the platelet glycoprotein complex Ib-V-IX. In our study,
      we analyzed 300 samples including those of patients with hereditary von
      Willebrand disease. The results obtained with the HaemosIL assay were compared to
      von Willebrand factor activities determined by established procedures. Activities
      determined with HaemosIL correlated with those activities determined as
      ristocetin cofactor (r = 0.88, p < 0.0001), collagen-binding (r = 0.93, p <
      0.0001), and GP Ib-binding (r = 0.91, p < 0.0001). The comparability of results
      obtained by HaemosIL and the GP Ib-binding ELISA were excellent ([HaemosIL] =
      0.96 infinity activity [GP Ib-binding ELISA] + 10.7), whereas activities
      determined by ristocetin cofactor or collagen-binding revealed more variance.
      Like the other assays, the HaemosIL failed to indicate a loss of high-molecular
      weight von Willebrand factor multimers. The HaemosIL assay can replace the GP Ib
      binding ELISA for the determination of von Willebrand factor activity. Advantages
      of this assay include accuracy of results, full automation, and, thus, broad
      availability. Since the assay does not predict the absence of high-molecular
      weight multimers, multimeric analysis remains the procedure of choice for the
      differentiation of functional defects.

PMID- 16959684
TI  - Modulatory effects of Escherichia coli capsular-derived sulfaminoheparosans and
      heparins on tissue factor-mediated activation of platelets: flow cytometric
      analysis.
AB  - Sulfaminoheparosans (alternatively known as bioheparins) represent sulfated
      derivatives obtained from the K5 capsular polysaccharide of Escherichia coli.
      Previous studies have shown that these agents are structurally comparable to
      heparins and capable of exerting anticoagulant and antiprotease effects like
      heparins. Furthermore they are also able to release tissue factor pathway
      inhibitor (TFPI). Tissue factor (TF) plays a vital role in the pathogenesis of
      thrombotic and cardiovascular disorders. Anticoagulants such as heparins and
      bioheparins inhibit this thrombogenic mediator and thereby downregulate the
      activation of prothrombin and factor X. This study was carried out to determine
      the effects of several bioheparin fractions and heparins on TF-mediated platelet
      activation and their direct effect on platelets using human whole blood flow
      cytometry. Four different sulfaminoheparosan fractions with mean molecular
      weights of 20, 9, 7, and 6 kDa were tested for their inhibitory effects on
      platelet activation at two different concentrations (100 and 10 microg/mL).
      Unfractionated heparin and a low-molecular-weight heparin, tinzaparin, were also
      tested under the same experimental conditions for comparative modulatory
      responses. Fresh whole blood from healthy female and male volunteers (n = 5) was
      mixed with each of these agents and incubated with TF (diluted thromboplastin C)
      to activate platelets. Platelets were labeled with the antibodies CD61 FITC (GP
      IIIa) and CD62 PE (P-selectin). The data were analyzed in terms of percent
      platelet aggregation and platelet P-selectin expression. At 100 microg/mL, all of
      these agents strongly and significantly inhibited (approximately 40%) the
      platelet activation induced by TF in comparison to saline control. The inhibitory
      effects of each of these agents were slightly weaker (approximately 24%
      inhibition) at 10 microg/mL. The inhibitory effects of these agents on P-selectin
      expression correspond to their effects on platelet aggregation. At 100 microg/mL
      all the agents produced greater than 80% inhibition of P-selectin expression
      whereas at 10 microg/mL, the inhibition is greater than 70% except for bio-20
      kDa, which produced less than 50% of inhibition. No molecular weight dependence
      was observed with bioheparin fractions in terms of inhibitory effects on platelet
      aggregation or P-selectin expression. None of the bioheparins and heparins
      exhibited any direct effects on platelets. These observations suggest that both
      the bioheparins and heparins are capable of inhibiting TF-mediated activation of
      platelets. Thus the therapeutic effects of bioheparins in the TF-mediated
      pathogenesis of platelet activation may be similar to those of heparins.

PMID- 16959685
TI  - Diabetic ulcers: microcirculatory improvement and faster healing with pycnogenol.
AB  - Diabetic microangiopathy leads to lower limb ulcers that are very slow to heal.
      Pycnogenol was evaluated on diabetic ulcers in a controlled trial. Ulcer
      medications were used in 4 groups (30 patients): (1) systemic Pycnogenol and
      local application; (2) local Pycnogenol only; (3) oral Pycnogenol; and (4)
      medications only (control group). Ulcerated areas and symptom scores were more
      reduced with the combined oral and local treatment (P < .05). Oral and local
      treatment were less effective, but still improved compared with the controls.
      Combined treatment produced 89% complete healing at 6 weeks versus 84% with local
      treatment and 85% with oral treatment; healing in controls was 61%. The combined
      treatment group and oral only group had better microcirculation after the
      combined treatment. Combined local and systemic application of Pycnogenol may
      offer a new treatment of diabetic ulcers. Local treatment also speeds ulcer
      healing.

PMID- 16959686
TI  - Specific determination of plasmatic thrombin activity.
AB  - Thrombin is the key enzyme of coagulation. Its activity can be determined via
      fibrinogen O fibrin conversion or via cleavage of a chromogenic substrate. The
      latter method is easier than the first one, but in plasma it is hampered due to
      unspecific cleavage of the chromogenic substrate by thrombin-like enzymes of
      hemostasis, especially those of the contact phase. The concentration of the
      thrombin substrate (HD-CHG-Ala-Arg-pNA) was optimized, using final substrate
      concentrations of 0 to 5 mM, a final arginine concentration of 1.13 M, and
      samples of 10 mIU/mL purified thrombin in 7% human albumin or pooled normal
      citrated plasma without and with EDTA. Twenty microliters pooled normal citrated
      plasma (frozen/thawed) or factor II-deficient plasma (lyophilized) were incubated
      with 10 microL 0% to 0.5% Thromborel S (100% = 162 ng/mL tissue factor [TF]) in
      6% BSA or with 10 microL 0% (physiol. NaCl) to 50% Pathromtin SL and with 20
      microL 25 mM CaCl(2). After 0 to 22 minutes (37 degrees C), 20 microL 1.7 M
      arginine, pH 8.7 were added. Fifteen microliters 0.9 mM HD-CHGAla-Arg-pNA in 2.3
      M arginine, pH 8.6, were added and the increase in absorbance (deltaA) at 405 nm
      was determined. Thrombin activity was standardized against the (3)A measured for
      1 IU/mL thrombin in 7% human albumin (8.8 mA/min RT). The optimal final
      chromogenic substrate concentration to detect thrombin in this assay system is
      less than 0.6 mM. Higher substrate concentrations in a plasma milieu result in
      unspecific cleavage of the substrate. Using final concentrations of chromogenic
      substrate less than 0.4 mM (the approximate Km- value for thrombin) and final
      concentrations of arginine greater than 800 mM, in factor II-depleted plasma,
      when activated either by TF or by the contact phase, there is no significant
      thrombin generation. The circulating thrombin activity measured in EDTA plasma of
      39 healthy donors is 100 +/- 20% of norm (mean value +/- 1 SD; 100% = 5.5 mIU/mL
      thrombin). This chromogenic assay detects thrombin activity independent of
      clotting seconds or fibrin mediated turbidity increases. This technique allows to
      standardize the thrombin activity generated in any biologic system in
      international thrombin units.

PMID- 16959687
TI  - C-reactive protein in hypertensive disorders in pregnancy.
AB  - Hypertension is the most frequent medical complication of pregnancy. A recent
      report demonstrates the flogistic pathogenesis of pregnancy-induced hypertension.
      Because C-reactive protein (CRP) is a marker of inflammation, it can be used in
      the differential diagnosis of hypertensive disorders of pregnancy. A total of 322
      pregnant women at 24 to 32 weeks' gestation were enrolled. The control group (A)
      comprised 190 women. Sixty-three women had preeclampsia (PE, group B), 31 women
      presented transient hypertension (TH, group C), 19 had HELLP syndrome (HS, group
      D) and 19 had chronic hypertension (CH, group E). CRP serum concentrations were
      significantly higher in groups B, C, and D in comparison with the group A. In the
      whole population, systolic and diastolic pressure value inversely correlate with
      weight at delivery and weeks of gestation at delivery. CPR levels in patients
      with PE and HS inversely correlate with birth weight and gestational week at
      delivery. Normal plasma levels of CRP may be an important marker of differential
      diagnosis between TH and CH. In TH, PE, and HS, CRP levels were higher than in
      the control and CH groups, suggesting that inflammation may be the common
      pathogenetic cause of TH and PE. Finally CRP levels in preeclampsia are believed
      to correlate with preeclamptic process severity.

PMID- 16959688
TI  - Fibrinogen Seoul (FGG Ala341Asp): a novel mutation associated with
      hypodysfibrinogenemia.
AB  - Dysfibrinogenemia is a coagulation disorder caused by a variety of structural
      abnormalities in the fibrinogen molecule that result in fibrinogen function. The
      molecular basis of hypodysfibrinogenemia was investigated in a 66-year-old woman
      with peripheral artery obstructive disease and in her family members. Plasma
      level of functional fibrinogen determined using the Clauss method was lower (75
      mg/dL; normal, 140-460 mg/dL) than that measured with immunologic nephelometric
      assay (137 mg/dL; normal, 180-400 mg/dL). Similar results were also observed in
      two family members through two generations. DNA was extracted from whole blood,
      and the coding regions and intron/exon boundaries of gamma chain gene (FGG) were
      amplified. A novel (Fibrinogen Seoul) heterozygous FGG mutation (GCT->GAT,
      Ala341Asp) was identified in all three affected family members. Thrombin
      catalyzed polymerization was found to be defective on the analysis of purified
      fibinogen from the propositus. Molecular modeling also showed a conformational
      change of fibrinogen structure.

PMID- 16959689
TI  - A new clinical model in pulmonary embolism and its correlation with V/P scan
      results.
AB  - The study was prospectively designed to assess the correlation between a new
      clinical model empirically developed for acute pulmonary embolism (PE) and
      ventilation/perfusion (V/P) scan results. One hundred sixty consecutive patients
      with suspected acute PE underwent clinical evaluation before V/P scintigraphy.
      The clinical probability of PE was categorized according to a structured clinical
      model empirically developed as low, intermediate, or high, and the results were
      compared with those of V/P scintigraphy. Forty, 61, and 59 patients were
      classified as low, intermediate, and high clinical probability, respectively.
      Seventy-five percent (30/40) of the patients with low clinical probability were
      also of low scintigraphic probability or had a normal result (r(s): 0.39,
      p=0.000); 28% (17/61) of the patients with intermediate clinical probability
      demonstrated intermediate scintigraphic probability (r(s): 0.20, p=0.012); and
      68% (40/59) of the patients with high clinical probability were also of high
      scintigraphic probability (r(s): 0.43, p=0.000). Overall, the correlation of two
      scoring systems was statistically significant (r(s): 0.39, p=0.000). Unilateral
      leg swelling (p=0.027), syncope or near syncope (p=0.002), amputation of a hilar
      artery (p=0.007), and electrocardiographic signs of right ventricular overload
      (p=0.000) prevailed in patients with high scintigraphic probability. "Syncope
      near syncope or hemodynamic collapse" PLUS "electrocardiographic signs of right
      ventricular overload or hypoxemia" combination had the most significant
      correlation with a high scintigraphic probability (r(s): 0.31; p=0.000). In
      conclusion, the new clinical model empirically developed was significantly
      successful to provide comparable results with V/P scan. This consistency was
      particularly prominent in patients with low or high clinical probability for PE.

PMID- 16959691
TI  - Spontaneous thrombolysis: a forgotten determinant of life or death.
AB  - Substantial evidence suggests that spontaneous thrombolytic activity of blood is
      an effective mechanism for protection against tissue damage that is the
      consequence of lasting arterial occlusion. Despite the generally held belief that
      coronary artery disease and stroke are preventable, a promising avenue of
      prevention, namely the identification and prophylactic treatment of those at risk
      of inefficient spontaneous thrombolysis, has been neglected. This is mainly due
      to the lack of physiologically relevant test. A recently described technique
      allows the measurement of spontaneous thrombolysis, that is, lysis of an
      autologous platelet-rich thrombus in the absence of added plasminogen activators.
      Early results suggest that this test may have significant clinical potential both
      in identifying those at risk from fatal thrombotic event and in finding new
      therapeutic avenues of improving spontaneous thrombolytic activity.

PMID- 16959690
TI  - A pilot study of the effects of Vivostat patient-derived fibrin sealant in
      reducing blood loss in primary hip arthroplasty.
AB  - A pilot study evaluated the effectiveness of Vivostat patient-derived fibrin
      sealant in reducing blood loss in patients who underwent primary hip
      arthroplasty. Eighty adult patients undergoing elective surgery were randomized
      to receive either Vivostat sealant or control (no additional hemostatic
      treatment). Patients allocated Vivostat sealant donated 120 mL of blood, which
      was then processed perioperatively to produce a fibrin sealant that was applied
      to the bleeding wound surfaces just before closure. Transfusion requirements,
      blood loss during surgery, drain volumes, and daily hematocrit and hemoglobin
      levels were measured. Hospitalization times, adverse events, and postoperative
      wound complications were also monitored. Blood loss during surgery and wound
      drainage volume was lower in the Vivostat group than in the control group,
      although the differences were not significantly different. Transfusion
      requirements (median, 270 mL of packed red blood cells) and hospitalization times
      (both median 7 days) were the same for both groups. No adverse events related to
      the use of Vivostat occurred. There were indications of a possible reduction in
      the incidence of postoperative wound oozing (15% vs 25%) and hematomas (6% vs
      11%) with the use of Vivostat compared with the control group, although
      differences were not statistically significant. In conclusion, in this pilot
      study, use of Vivostat patient-derived fibrin in hip arthroplasty was not
      associated with a significant reduction in blood loss. Further studies, with
      larger numbers of patients, may be warranted to investigate a possible benefit of
      Vivostat in reducing postoperative wound complications.

PMID- 16959692
TI  - Decrements in the thrombin activatable fibrinolysis inhibitor (TAFI) levels in
      association with orlistat treatment in obesity.
AB  - Obesity and its associated metabolic complications can impair the physiologic
      regulation of fibrinolysis, leading to a hyper coagulable state. We aimed to
      assess circulating thrombin activatable fibrinolysis inhibitor (TAFI) levels in
      obese female patients and to test the effects of orlistat-induced weight loss on
      basal TAFI concentrations. Obese female outpatients age 18 and older, with a body
      mass index (BMI, calculated as weight in kilograms divided by the square of
      height in meters) of at least 30, were included into the study. Thirteen nonobese
      (median BMI, 22.60 kg/m(2)) age-matched females were taken as controls. Plasma
      TAFI levels were measured before orlistat administration and after 6 months of
      orlistat treatment in the obese group and only one measurement was done in the
      control group. Twenty-seven obese patients were recruited into the study. The
      median TAFI level of the control group was 124.00; this value was significantly
      lower than the basal TAFI level of the obese group (p < 0.001). TAFI levels after
      orlistat therapy were statistically significantly lower than basal TAFI levels (p
      < 0.001) in the obese group. Hemostatic abnormalities including TAFI alterations
      represent a link between obesity and vascular thrombosis. Effective interventions
      should be considered in improving the obesity-associated prothrombotic risk
      profile.

PMID- 16959693
TI  - Assessment of total thrombus load in symptomatic patients with venous
      thromboembolism.
AB  - Pulmonary embolism (PE) and Deep vein thrombosis (DVT) are separate but related
      aspects of the same dynamic process termed as venous thrombembolism (VTE). The
      existing Asian literature has shown a wide variation in the prevalence of VTE,
      with very limited data from the Indian subcontinent. Between January 2001 and
      July 2004, 1,552 patients with clinically suspected lower limb DVT underwent a
      combined ascending radionuclide venogram and lung perfusion scan for assessment
      of the total thrombus burden. Of 744 patients with radionuclide venography proven
      DVT, 294 (40%) had a high probability lung scan. Nearly half of these patients
      were asymptomatic for pulmonary embolism. The high prevalence of PE in patients
      with DVT suggests the need for evaluation of thrombus load in the venous as well
      as pulmonary circulation. A combination radionuclide ascending venography with
      lung perfusion scan is a useful and reliable single test for this purpose.

PMID- 16959695
TI  - Recent findings for anti-metastatic potential of heparin.

PMID- 16959694
TI  - Report of a patient with heparin-induced thrombocytopenia type II associated with
      IgA antibodies only.
AB  - Heparin-induced thrombocytopenia type II (HIT II) is usually mediated by
      immunoglobulin G (IgG) antibodies that lead to platelet activation via the
      FcgammaIIA-receptor. Here we describe a patient who developed HIT II after
      aortocoronary bypass surgery. His serum contained an antibody that was detectable
      by the heparin-induced platelet activation assay (HIPA) and by the ID-HPF4
      particle agglutination assay. The flow cytometric analysis showed that the
      antibody was of the IgA class.

PMID- 16959696
TI  - Is Yasmin as safe as other contraceptive pills?

PMID- 16959697
TI  - The potential of comparative genomic hybridization as a tool in the differential
      diagnosis of matrix-producing bone lesions.
AB  - Matrix-producing bone lesions consist of a wide variety of benign and malignant
      conditions. With respect to morphology, an overlap exists between benign and
      malignant bone tumors that causes difficulties in the final determination of the
      tumor. This study was conducted to show the potential of comparative genomic
      hybridization as a tool in the differential diagnosis of matrix-producing bone
      lesions. Thirty benign bone tumors were evaluated by conventional comparative
      genomic hybridization. To test its diagnostic reliability, 5 additional cases
      were analyzed, all with differential diagnostic difficulties related to
      morphology and radiology. All were ultimately diagnosed as malignant sarcomas,
      and unbalanced alterations were detected. In contrast benign tumors or tumor-like
      lesions did not reveal any chromosomal alterations. Comparative genomic
      hybridization is a useful adjunct in the complicated differential diagnostic
      algorithms of matrix-producing bone tumors.

PMID- 16959698
TI  - Pediatric sclerosing rhabdomyosarcoma.
AB  - Sclerosing rhabdomyosarcoma, a particular phenotypic variant of rhabdomyosarcoma
      initially described in the adult population, has emerged as a potential pitfall
      in the evaluation of pediatric sarcomas. Because of its densely hyalinized
      collagenous matrix and its occasional expression of a pseudovascular pattern of
      growth, sclerosing rhabdomyosarcoma has been at times misdiagnosed as
      chondrosarcoma, osteosarcoma, or angiosarcoma. We describe 3 pediatric patients
      with sclerosing rhabdomyosarcoma and provide a detailed description of its
      distinguishing pathologic features. Awareness about this rhabdomyosarcoma variant
      and careful immunophenotypical evaluation are necessary to establish the correct
      diagnosis. Although no specific genetic aberrations have been recognized, yet the
      cytogenetic findings in 2 tumors of this series suggest a link with embryonal
      rhabdomyosarcoma. It is likely that further genotyping will result in better
      nosologic delineation of sclerosing rhabdomyosarcoma and that it will uncover
      pathogenetically and prognostically relevant genes.

PMID- 16959699
TI  - Enterocolic lymphocytic phlebitis: statistical analysis of histology features in
      viable and ischemic bowel.
AB  - Enterocolic lymphocytic phlebitis is a rare cause of segmental ischemic
      enterocolitis. This artery-sparing transmural vasculitis is classically a
      circumferential phlebitis with perivenular lymphocyte cuffing and thrombi in the
      absence of systemic manifestations. Myointimal hyperplasia may represent a
      chronic phase of enterocolic lymphocytic phlebitis. Subclinical or early stage
      enterocolic lymphocytic phlebitis is not well delineated. We analyzed 600
      submucosal and subserosal veins from both ischemic and intact bowel segments to
      discern if vascular morphology varied between sites. Crescentic and
      circumferential lymphocytic phlebitis is more common in viable bowel than in the
      ischemic segment. A nonsignificant trend was found for increased crescentic
      morphology between intact bowel remote from the ischemic focus compared with that
      adjacent to the ischemic focus. Hallmarks of ischemic bowel are necrotizing
      phlebitis and thrombi formation. Thrombophlebitis morphology is distinctly
      different in viable and ischemic bowel, changing from the classic lymphocytic to
      necrotizing lesions respectively.

PMID- 16959700
TI  - Merkel cells in the oral mucosa.
AB  - Ninety-eight consecutive surgical biopsies of oral mucosa from 96 patients were
      evaluated immunohistochemically with an anti-cytokeratin 20 (CK 20) anti-body to
      evidence Merkel cells (MC). Fifteen cases, showing the highest number of MC, were
      additionally studied with chromogranin A, S-100 protein, neuro filaments,
      epithelial membrane antigen, and double immunostaining for CK 20 and Ki67
      antibodies to evaluate MC proliferation. Electron microscopy was performed in 2
      cases. MC were observed in 58 cases. The highest number of MC was found in the
      gingival, buccal, and palate mucosa, especially in chronically damaged oral
      mucosa (lichen and chronic aspecific inflammation) as well as in the mucosa
      overlying tumors rather than in normal or acute inflammation. MC were not
      observed in dysplastic or neoplastic epithelium. MC showed evidence of
      proliferation, as demonstrated by Ki67 positivity, in 3 cases. In conclusion, MC
      appear to play a role in the reparative processes of oral mucosa.

PMID- 16959701
TI  - Beta-catenin and E-cadherin expression in salivary gland tumors.
AB  - This study evaluated the expression of E-cadherin and beta-catenin in salivary
      gland tumors. Twelve biopsy specimens from cases diagnosed as pleomorphic
      adenoma, 17 adenoid cystic carcinomas, 10 epithelial-myoepithelial carcinomas,
      and 4 polymorphous low-grade adenocarcinomas were immunohistochemically labeled
      for E-cadherin and beta-catenin antibodies. Healthy salivary glands were used as
      controls. Membrane-associated E-cadherin and beta-catenin expression was present
      in all the tumor types studied. E-cadherin and beta-catenin showed a similar
      distribution; however, beta-catenin labeling was weaker than that for E-cadherin.
      In the epithelial-myoepithelial carcinomas, myoepithelial cells exhibited diffuse
      nuclear staining, although occasional cells presented only focal labeling.
      Epithelial-myoepithelial carcinomas present changes in [.beta]-catenin expression
      but the other salivary tumors studied do not, which may reflect divergence in
      tumorigenesis of this extensive subset of salivary gland tumors.

PMID- 16959702
TI  - Unusual renal pathology associated with a Wilms tumor in a 15-month-old infant.
AB  - Beckwith-Wiedemann syndrome is an overgrowth dis-order that predisposes to the
      development of a variety of malignancies including Wilms tumor. Pathologists may
      suspect the presence of Beckwith-Wiedemann syndrome, which may be clinically
      subtle, on the basis of the histopathology of the renal parenchyma adjacent to a
      Wilms tumor. These kidneys typically harbor multiple nephrogenic rests
      (especially perilobar nephrogenic rests), and their medullas have blunted
      papillae resulting from excessive fibromyxoid stroma, decreased collecting ducts,
      and decreased Henle loops. This complex of findings constitutes the so-called
      Beckwith Medulla. Extensions of this stroma-rich medulla into the cortex results
      in characteristic dysplastic medullary-ray nodules. Identification of these
      histologic abnormalities by the pathologist should prompt the clinician to
      evaluate the child for Beckwith-Wiedemann syndrome. Proper screening of these
      children can allow for early detection of cancers and treatment while these
      cancers are curable.

PMID- 16959703
TI  - Images in pathology. Mammotome footprints: histologic artefacts in the era of
      stereotactic vacuum mammotome biopsy.

PMID- 16959704
TI  - Images in pathology. Solid and cystic cell nests.

PMID- 16959707
TI  - Images in pathology. A doggy face in an ugly neoplasm.

PMID- 16959708
TI  - Images in pathology. Signet ring cells in an endometrial biopsy: tumor or not
      tumor? That is the question.

PMID- 16959709
TI  - Images in pathology. An "expressionist" portrait of mummy liver.

PMID- 16959710
TI  - Malignant mesothelioma masquerading as a multinodular bronchioloalveolar cell
      adenocarcinoma with widespread pulmonary nodules.
AB  - A 72-year-old man had a unilateral pleural effusion and multiple bilateral
      pulmonary nodules. Thoracoscopic biopsy revealed multiple discrete nodules in the
      pleura and lung. The latter consisted of tall columnar malignant cells arranged
      on alveolar surfaces in a lepidic growth pattern. Mucin filled the alveolar
      lumina, both in the nodules and surrounding lung. It stained with Alcian blue but
      not with periodic acid Schiff, suggesting that it was a glycosaminoglycan, which
      was confirmed as hyaluronic acid by complete digestion with hyaluronidase. Tumor
      cells were calretinin, Wilms tumor-1, and high-molecular-weight cytokeratin 5/6
      positive, and were negative for thyroid transcription factor-1, cytokeratin 7,
      and cytokeratin 20. Ultrastructurally, they had very long and abundant, slender
      microvilli typical of a malignant mesothelioma. This is the first example of a
      mesothelioma masquerading as a bronchioloalveolar carcinoma.

PMID- 16959711
TI  - Exclusive intrapulmonary lepidic growth of a malignant pleural mesothelioma
      presenting with pneumothorax and involving the peritoneum.
AB  - We report a rare case of malignant pleural mesothelioma presenting clinically
      with pneumothorax and histologically with an exclusive intrapulmonary lepidic
      growth. Neither intrathoracic nodules nor pleural thickening were found. The
      patient subsequently experienced acute abdominal pain with peritonitis and
      intestinal occlusion by peritoneal mesothelioma. The morphologic clues leading to
      the correct diagnosis of mesothelioma with prominent intrapulmonary growth are
      briefly discussed.

PMID- 16959712
TI  - Alveolar rhabdomyosarcoma of the paranasal sinuses in a 57-year-old woman with
      1:16 translocation.
AB  - Alveolar rhabdomyosarcoma is an uncommon tumor. It is a rare malignancy in adults
      and rarely occurs in paranasal sinuses in those aged older than 50 years. This
      report describes a locally invasive and destructive alveolar rhabdomyosarcoma
      arising in the ethmoid sinus of a 57-year-old woman. The small round blue cell
      tumors are positive for myogenin by immunohistochemistry and have a karyotype of
      45, XX, -5, -13, der(16)t(1;1) (q21;q13) by cytogenetic analysis. Fluorescence in
      situ hybridization demonstrated a complex translocation with break apart of the
      FKHR region, which supports a diagnosis of alveolar rhabdomyosarcoma. This report
      characterizes this tumor through microscopic and cyto-genetic analysis and
      emphasizes the importance of considering rhabdomyosarcoma in the differential
      diagnosis of small round cell tumors of the head and neck region in the middle
      aged adults.

PMID- 16959713
TI  - Tubular adenocarcinoma of the thymus: case report and review of the literature.
AB  - Primary carcinomas of the thymus are rare. A variety of histologic patterns have
      been reported, and the most common are squamous cell carcinoma, lymphoepithelioma
      like carcinoma, and basaloid carcinoma. Adenocarcinomas of the thymus are
      extremely rare. As determined from a literature search, a pure tubular
      adenocarcinoma has never been previously described, and thus, this is first case
      report of tubular adenocarcinoma of the thymus. A combined resection of the
      superior vena cava and pericardium was performed. Immunohistochemically, the
      tumor cells were positive for CD5.

PMID- 16959714
TI  - A primary pure yolk sac tumor of the lung exhibiting CDX-2 immunoreactivity and
      increased serum levels of alkaline phosphatase intestinal isoenzyme.
AB  - Malignant extragonadal germ cell tumors primary to the lung are quite uncommon
      lesions, but pure yolk sac tumor is even more exceptional. This is believed to be
      the first reported case of yolk sac tumor of the lung in which an intense and
      diffuse immunoreactivity for CDX2, a marker of intestinal differentiation
      reportedly expressed also in gonadal yolk sac tumor, was associated with
      increased serum levels of the alkaline phosphatase intestinal isoform. Nine
      months after radical surgery and adjuvant chemotherapy, the patient is alive and
      well without evidence of recurrent or metastatic disease and with serum levels of
      the alkaline phosphatase intestinal isoform within normal limits. The pathologist
      should be aware of yolk sac tumor arising in the lung and that alkaline
      phosphatase intestinal isoform could become an additional serum marker for such a
      tumor.

PMID- 16959715
TI  - Gastrointestinal stromal tumor colliding with angiosarcoma.
AB  - The collision of gastric tumors is rare, and those involving gastrointestinal
      stromal tumor and angiosarcoma have not been previously reported. This article
      reports a gastric tumor involving collision of gastrointestinal stromal tumor and
      angiosarcoma. The patient was an 81-year-old man who presented with dyspepsia and
      large gastric mass. The mass showed a proliferation of spindle cells expanding
      the muscularis propria. Most of the tumor consisted of spindle cells with low
      grade cytology that were positive for CD117 (c-kit), indicating gastrointestinal
      stromal tumor. Occasional prominent foci showed dissecting and anastomosing
      channels of ectatic vascular spaces lined by cytologically malignant cells that
      were positive focally for CD117 and diffusely positive for multiple vascular
      markers, indicating angiosarcoma.

PMID- 16959716
TI  - Primary peritoneal epithelioid hemangioendothelioma.
AB  - Epithelioid hemangioendothelioma is an uncommon malignant vascular tumor of
      intermediate grade that occurs in a variety of organs and soft tissues. Diagnosis
      of epithelioid hemangioendothelioma is often complicated by the rarity of the
      tumor, and because the tumor shares many morphologic features with other
      peritoneal neoplasms. This report presents 3 cases of epithelioid
      hemangioendotheliomas arising as primary tumors of the peritoneum and reviews 7
      previously reported cases to establish the demographic, clinical, morphologic,
      immunohistochemical, and ultrastructural features of this neoplasm. These cases
      demonstrate that the light microscopic features are very similar to epithelioid
      hemangioendothelioma arising at more conventional sites, such as the liver, that
      immunohistochemical analysis provides a reliable approach for confirming or
      establishing the diagnosis, and that at least one endothelial marker (either
      CD31, CD34, or factor VIII) should be positive for a definitive diagnosis. This
      series identifies the characteristics of peritoneal epithelioid
      hemangioendothelioma that can be reliably used for diagnosis.

PMID- 16959717
TI  - Remarkably high frequency of EGFR expression in breast carcinomas with squamous
      differentiation.

PMID- 16959718
TI  - Platelet function and pharmacologic inhibition.
AB  - Platelets have traditionally been understood within the context of hemostasis and
      hemorrhagic disorders. However, with increasing procedures being performed in
      smaller vessels and with an increasing incidence of atherosclerosis, the often
      critical role platelets play is more evident. Platelets are no longer viewed as
      "scaffolding" for the events of the coagulation cascade but rather as important
      catalysts in hemostasis, thrombosis, and fibrinolysis. Improved understanding of
      platelet physiology has led to developments of pharmacologic adjuncts resulting
      in improved patency rates and improved patient outcomes. This review addresses
      the physiology of platelet function and the impact of new pharmacologic agents in
      percutaneous intervention.

PMID- 16959719
TI  - Laser atherectomy for lower extremity revascularization: An adjunctive
      endovascular treatment option.
AB  - Excimer laser atherectomy (LA) employs precision laser energy control (shallow
      tissue penetration) and safer wavelengths (ultraviolet as opposed to the infrared
      spectra in older laser technology), which decreases perforation and thermal
      injury to the treated vessels. Though extensively used by cardiologists for
      severe obstructive coronary artery disease, peripheral interventionalists have
      not accepted LA as a routine adjunctive technique for stenotic or occluded
      vessels. We report herein the technical and clinical outcomes with LA for complex
      peripheral vascular disease in patients deemed high-risk for conventional
      surgical revascularization. Over a 6-month period, 19 lesions in 15 high-risk
      patients (mean age 72 +/-10 years) were treated with LA (308-nm spectral
      wavelength) followed by balloon angioplasty for limb-threatening ischemia (n =
      10) and severe disabling claudication (n = 5). The lesions were located at the
      superficial femoral artery (n = 8), popliteal artery (6), and/or tibial vessels
      (5). The mean occlusion length was 10.3 +/-2.3 cm. Laser catheter choice ranged
      from 1.4 to 2.5 mm depending on the target vessel diameter. Clinical examination,
      duplex ultrasound, and ankle-brachial indices were performed in follow-up visits.
      Immediate technical success was achieved in 16 (84%) lesions. In the 3 technical
      failures, inability to cross the lesion with a wire (n = 2) or vessel perforation
      (n = 1) precluded successful LA. Overall, primary patency as assessed by duplex
      was 57% (superficial femoral artery 71%, popliteal 60%, tibial vessels 25%).
      Clinical improvement was seen in 10 lesions (77%) that were successfully treated
      initially. One patient required below-knee amputation. At an average of 2-year
      follow-up, 6 patients who were initially successfully treated were alive (46%),
      including 3 patients (50%) with stable symptoms without the need for major
      amputation. Laser atherectomy is a useful adjunctive revascularization technique
      for high-risk patients with limb-threatening ischemia. This technique is
      especially beneficial in the treatment of ostial lesions, which may be prone to
      distal embolization, as well as total occlusions that can be traversed by a guide
      wire but not a balloon. Vascular surgeons should add LA to their endovascular
      armamentarium for the treatment of complex peripheral vascular disease in the
      high surgical risk patients. Further study of clinical outcome measures and
      comparison to other interventional techniques are warranted.

PMID- 16959720
TI  - The use of covered nitinol stents to salvage dialysis grafts after multiple
      failures.
AB  - The increasing number of patients requiring hemodialysis and the limited number
      of access sites have resulted in an increase in multiple graft revisions to
      maintain access for hemodialysis. Venous outflow or anastomotic stenoses in
      vascular grafts tend to recur and contribute to the difficulty in maintaining a
      functioning graft. Thus, extending the life of a failed graft becomes an
      important objective of this study, which was to assess the use of covered nitinol
      stents to salvage expanded polytetrafluoroethylene (ePTFE) grafts with venous
      anastomotic or outflow stenosis that have failed after multiple revisions. This
      is a review of 8 failed non-autogenous ePTFE grafts with isolated venous
      anastomotic or proximal outflow stenoses that had undergone multiple previous
      revisions, had failed percutaneous transluminal angioplasty (PTA), and required
      placement of a covered nitinol stent. Graft locations were forearm (2), upper arm
      (4), and femoral (2). The mean number of interventions per patient before stent
      placement was 5.87 thrombectomies (range 2-28) and 3.38 balloon angioplasties
      (range 2-19). Five patients had 0.62 interposition grafting and 3 had patch
      angioplasty. All 8 patients (100%) underwent successful dialysis after
      thrombectomy and stenting. The primary and secondary patency rates after stent
      placement were 50% and 75%, and 25% and 75%, at 3 and 6 months, respectively.
      Percutaneous thrombectomy, balloon angioplasty, and concomitant covered nitinol
      stent placement extend the function of hemodialysis access grafts that have
      previously failed multiple times.

PMID- 16959721
TI  - Peripheral arterial embolism: prevalence, outcome, and the role of
      echocardiography in management.
AB  - The aims of this study were to review the prevalence and outcome of all
      surgically treated upper and lower limb emboli presenting to one vascular unit in
      the last 3 years and to compare transthoracic with transesophageal
      echocardiography for defining the source of the embolus. All patients who
      underwent surgical embolectomy for acute limb ischemia from January 2001 to June
      2004 were reviewed. Transthoracic and transesophageal echocardiography were
      carried out on a subset of consecutive unselected patients. Forty-two patients,
      with a mean age of 80 years, underwent surgical embolectomy from January 2001 to
      June 2004 (M/F 1:1.8): 27 for lower limb ischemia and 15 for upper limb ischemia.
      Two thirds of these patients were found to be in atrial fibrillation at
      presentation (n = 28), of whom less than a third were receiving anticoagulants or
      antiplatelet agents (n = 8). The mean hospital stay was 15 days with 36 patients
      (86%) being fully anticoagulated before discharge from hospital. The 30-day
      mortality rate was 11% (n = 3/27) with 5 patients requiring fasciotomies (12%)
      and 3 patients requiring an amputation of the lower limb (11%). Postoperatively,
      34 patients (81%) had transthoracic echocardiography (TTE), which demonstrated a
      source or potential source for thrombus in 19 (56%). Fifteen patients (36%) had
      transesophageal echocardiography (TEE), which changed the subsequent management
      in 3 patients. All patients in whom TEE altered clinical management would have
      required this investigation if standard clinical guidelines were followed. TEE
      did not identify any additional patients with cardiac embolic sources that were
      not detected by TTE. Arterial limb emboli are still prevalent, but limb salvage
      and mortality rates appear to be improving. Despite clear guidelines on
      anticoagulation for patients in atrial fibrillation, many are not receiving
      appropriate treatment. Transthoracic echocardiography is a good screening tool
      for detecting a potential cardiac source for peripheral embolism, with
      transesophageal echocardiography being reserved for specific indications.

PMID- 16959723
TI  - Resistance within hemodialysis shunts predicts patency.
AB  - The authors examined the relationship between patency after thrombectomy of
      clotted dialysis grafts and intraoperative measurements of flow (Q), pressure
      gradient (PGR), and longitudinal resistance (RL). Eighteen thrombosed
      arteriovenous (AV) grafts underwent 21 thrombectomies. Pressures at arterial (P1)
      and venous (P2) ends of the AV grafts were determined with 22-gauge catheters and
      standard transducers; flow was measured with transit-time probes; arithmetic
      averaging of waveforms was used to compute mean Q, PGR, and RL. Kaplan-Meier
      patency curves were analyzed by using log rank methods. Mean patency for all
      grafts was 164 +/-152 days. For each variable, the 21 measurements were split and
      the patency curve for the grafts with the 11 lowest value grafts was compared to
      the curve representing the 10 highest value grafts. The difference between high
      RL versus low RL patency curves was significant with high-resistance grafts
      having a median patency of 55 days and low-resistance grafts having a median
      patency greater than 151 days (p = 0.0089). In contrast, the high Q group median
      patency was 151 days versus 174 days for the low Q group (p = 0.86). Median
      patency for the low PGR group was 115 days compared to 62 days for the high PGR
      group (p = 0.162). Longitudinal resistance within AV grafts, but not flow or
      pressure gradient, showed a significant correlation with patency after
      thrombectomy. Increased resistance to flow within AV grafts appears to be an
      important factor affecting the propensity of dialysis grafts to thrombose.

PMID- 16959722
TI  - Inferior vena cava filter placement in late-stage cancer.
AB  - Inferior vena cava (IVC) filters are increasingly used in patients with advanced
      stage cancer for prophylaxis of pulmonary embolus. We evaluated the survival
      benefit of placing IVC filters in patients with late-stage malignancy and
      assessed their effectiveness in preventing pulmonary embolism. Between 1998 and
      2003, 5,970 patients were treated with a primary diagnosis of malignancy at a
      tertiary care facility. Retrospective analysis identified 55 consecutive patients
      with stage III or IV malignant disease and venous thromboembolism (VTE) who
      received IVC filters. Retrospective review of electronic hospital charts
      identified subsequent pulmonary emboli, procedure-related complications, and
      survival. In a case control study, 16 patients with VTE but without IVC filter
      were matched for age, sex, type of malignancy, and stage of disease. IVC filter
      placement effectively prevented computed tomography (CT) scan or
      ventilation/perfusion ratio (V/Q) scan-proven pulmonary embolus in 52/55 (94.5%)
      patients. Complications developed in 4/55 or 7.3% of patients; 13/55 (23.6%)
      patients with late-stage cancer survived less than 30 days following placement of
      the filter. Another 23.6% of this group survived longer than 1 year. Ambulatory
      status differed significantly (p = 0.01) between these 2 subgroups. In the case
      control study, IVC filter placement conferred no survival benefit compared to the
      control group. One recurrent pulmonary embolism was observed in both the filter
      group and the control group. No deaths due to thromboembolic complications were
      observed in either group. In late-stage cancer, patient survival is limited
      primarily by the malignant process. While IVC filter placement is effective in
      preventing pulmonary emboli, there may be limited survival benefit in this
      particular patient population. However, there exists a subset of this population
      whose functional status predicts longer survival times after filter placement.

PMID- 16959724
TI  - Transcutaneous oxygen and carbon dioxide levels with iloprost administration in
      diabetic critical limb ischemia.
AB  - Iloprost, a prostacyclin analogue, is a treatment option for surgically
      unsuitable diabetic chronic critical limb ischemia (CLI), although its outcome is
      difficult to be anticipated clinically. Whether transcutaneous (tc) oxygen
      tension (PO2) predicts the response to iloprost in diabetic CLI is unclear at
      this point and, in that same context, the prognostic role of tc carbon dioxide
      tension (PCO2), another ischemia-sensitive parameter, is unknown. Supine and
      dependent tcPO2 and tcPCO2 were measured at baseline and after 4 weeks of
      iloprost treatment in 31 limbs of 26 type-2 diabetic angiopathies with CLI not
      amenable to surgery. Success was defined as pain relief and significant reduction
      of analgesics. Clinical outcome was stratified by baseline tcPO2 and tcPCO2
      tertiles, and likelihood ratios (LR) quantified the increase from pretest chances
      given a certain result. Iloprost succeeded in 16 (52%) and failed in 15 limbs
      (48%) and post-treatment tcPO2 followed a parallel course. Failures increased by
      ascending baseline tcPCO2 and descending tcPO2 tertiles; successes behaved
      specularly. Predictions of failure based on elevated tcPCO2 (>53 mm Hg) were more
      efficient than relying on depressed tcPO2 (LR 10.7 vs 3.6); success was almost
      certain when tcPO2 was >23 mm Hg (LR = 17.8). Dependent determinations were less
      useful than supine measurements for prognostic use. Elevated tcPCO2 predicted
      failure efficiently and high tcPO2 was a useful prognostic tool for success of
      iloprost, suggesting that their combined use may allow better prognostic
      stratification and improve the therapeutic approach to diabetic CLI.

PMID- 16959725
TI  - Optimal medical management of peripheral arterial disease.
AB  - Patients with peripheral vascular disease are less likely to receive optimal
      medical management than patients with coronary artery disease. However, early
      medical treatment is critical because it is profoundly beneficial and the
      benefits are maximized. Even in patients with advanced disease requiring invasive
      intervention, medical management has been proven to improve outcome, prolong the
      success of the intervention, improve functional capacity, and prolong life. The
      vascular surgeon should be knowledgeable enough to initiate basic medical therapy
      and to define for their patients the goals that need to be met to optimize their
      medical management. The vascular surgeon should be instrumental in assuring that
      the peripheral vascular patient receives medical therapy of the same standard as
      the patient with coronary disease. The major modifiable risk factors in the
      vascular patient are: smoking, high blood pressure, hyperlipidemia, physical
      inactivity, obesity, and diabetes. In addition, the use of beta blockers for
      patients with coronary disease and antiplatelet therapy as well as angiotensin
      converting enzyme (ACE) inhibitors are recommended for all patients with
      peripheral vascular disease. Statins have favorable effects on multiple
      interrelated aspects of vascular biology important in atherosclerosis. In
      particular they have beneficial effects on inflammation, plaque stabilization,
      endothelial dysfunction, and thrombosis. Statins have also been shown to be
      beneficial in acute vascular events. Angiotensin-converting enzyme inhibitors
      have been shown to reduce cardiovascular morbidity and mortality in patients with
      peripheral arterial disease regardless of the presence or absence of
      hypertension. A number of the pleiotropic effects of statins are shared by ACE
      inhibitors. In summary, patients with known vascular disease should be treated
      aggressively with a combination of a HMG CoA reductase inhibitor, an angiotensin
      converting enzyme inhibitor, an antiplatelet agent and a beta blocker if there is
      a history of coronary disease. They should also receive tight control of their
      blood pressure and blood sugar. Smokers should be encouraged to stop smoking and
      should be provided with pharmaceutical and emotional support by their physicians.
      All of these patients should have their body mass index as close to normal as
      possible and be on a therapeutic lifestyle diet. Regular aerobic exercise is also
      indicated. Patients with symptomatic claudication should be considered for
      cilostazol. Patients with multiple risk factors for vascular disease, but who do
      not have documented disease should also be on statin therapy. As more studies
      define the linear relationship between lower LDL-C levels and lowered risk of
      vascular events, indicating that the lower the LDL-C level, the lower the risk,
      experts are advocating more aggressive lipid-lowering therapy. In patients with
      peripheral arterial disease, some experts now advocate lowering the goal of LDL
      therapy to 70 mg/dL.

PMID- 16959726
TI  - Posterior tibial artery aneurysm: A case report.
AB  - Aneurysms of tibial vessels are extremely rare. The majority are pseudoaneurysms
      caused by trauma. Those that are true aneurysms have been associated with an
      inflammatory process or were mycotic in origin. We are reporting on a patient
      with a true posterior tibial artery aneurysm without any causative history. The
      aneurysm was repaired by resection and interposition of a reversed saphenous vein
      segment.

PMID- 16959727
TI  - Operative management of an aberrant splenic artery aneurysm: Utility of the
      medial visceral rotation approach: a case report and review of the literature.
AB  - The authors report an unusual case of a splenic artery aneurysm arising off the
      superior mesenteric artery. This was an incidental finding on computed tomography
      scan found during evaluation for a different or a separate disease process.

PMID- 16959728
TI  - Use of parietal peritoneum for aortic stump coverage following removal of an
      infected aortic prosthesis: A case report.
AB  - Aortic graft infections, albeit rare, pose a significant treatment challenge.
      Aortic stump disruption, in particular, is a potentially devastating
      complication. We describe a novel technique of using the parietal peritoneum to
      bolster a friable aortic stump in a 56-year-old man after an infected
      aortobifemoral graft was removed. The parietal peritoneal pedicle, in our
      experience, provides an effective alternative to reinforce an aortic stump when
      conventional coverage options have been exhausted.

PMID- 16959729
TI  - Endovascular repair of an infrarenal abdominal aortic aneurysm with a dominant
      middle mesenteric artery: A case report.
AB  - The middle mesenteric artery is a rare anomalous mesenteric vessel that may
      supply variable segments of the colon. Occlusion of this artery during
      endovascular aortic aneurysm repair may bear a significant risk of bowel
      ischemia. We report the successful interventional treatment of a patient with a
      5.3 cm infrarenal abdominal aortic aneurysm, sparing a dominant middle mesenteric
      artery.

PMID- 16959730
TI  - Suture line disruption after carotid endarterectomy.

PMID- 16959731
TI  - Digital noise reduction: an overview.
AB  - Digital noise reduction schemes are being used in most hearing aids currently
      marketed. Unlike the earlier analog schemes, these manufacturer-specific
      algorithms are developed to acoustically analyze the incoming signal and alter
      the gain/output characteristics according to their predetermined rules. Although
      most are modulation-based schemes (ie, differentiating speech from noise based on
      temporal characteristics), spectral subtraction techniques are being applied as
      well. The purpose of this article is to overview these schemes in terms of their
      differences and similarities.

PMID- 16959732
TI  - The effects of digital noise reduction on the acceptance of background noise.
AB  - Modern hearing aids commonly employ digital noise reduction (DNR) algorithms. The
      potential benefit of these algorithms is to provide improved speech understanding
      in noise or, at the least, to provide relaxed listening or increased ease of
      listening. In this study, 22 adults were fitted with 16-channel wide-dynamic
      range compression hearing aids containing DNR processing. The DNR includes both
      modulation-based and Wiener-filter-type algorithms working simultaneously. Both
      speech intelligibility and acceptable noise level (ANL) were assessed using the
      Hearing in Noise Test (HINT) with DNR on and DNR off. The ANL was also assessed
      without hearing aids. The results showed a significant mean improvement for the
      ANL (4.2 dB) for the DNR-on condition when compared to DNR-off condition.
      Moreover, there was a significant correlation between the magnitude of ANL
      improvement (relative to DNR on) and the DNR-off ANL. There was no significant
      mean improvement for the HINT for the DNR on condition, and on an individual
      basis, the HINT score did not significantly correlate with either aided ANL (DNR
      on or DNR off). These findings suggest that at least within the constraints of
      the DNR algorithms and test conditions employed in this study, DNR can
      significantly improve the clinically measured ANL, which may result in improved
      ease of listening for speech-in-noise situations.

PMID- 16959733
TI  - Amplification with digital noise reduction and the perception of annoying and
      aversive sounds.
AB  - Hearing aid users report difficulties using their hearing aids in noisy
      environments. Problems include understanding speech, loudness discomfort, and
      annoyance with background noise. Digital noise reduction algorithms have been
      promoted as a method to solve speech understanding and comfort in noise problems.
      Research has failed to find improved speech understanding in noise. Little is
      known about how digital noise reduction affects noise annoyance and aversiveness.
      The goals of this investigation were to determine how a specific digital noise
      reduction system affects hearing aid users' perception of noise annoyance and
      aversiveness and to compare their perceptions to those of normal-hearing
      listeners. Ratings of noise annoyance and of aversiveness were obtained from 49
      participants with moderate sensorineural hearing loss before fitting and after 3
      weeks of hearing aid use. Findings were compared to measures obtained from normal
      hearing listeners. Perceived annoyance and aversiveness increased with
      amplification. Annoyance and aversiveness with the hearing aid approximated
      normal perception. The results of this investigation suggest the need for
      counseling patients about realistic expectations related to annoyance and
      aversiveness of sounds at the time of hearing aid fitting.

PMID- 16959734
TI  - New perspectives on assessing amplification effects.
AB  - Clinicians have long been aware of the range of performance variability with
      hearing aids. Despite improvements in technology, there remain many instances of
      well-selected and appropriately fitted hearing aids whereby the user reports
      minimal improvement in speech understanding. This review presents a multistage
      framework for understanding how a hearing aid affects performance. Six stages are
      considered: (1) acoustic content of the signal, (2) modification of the signal by
      the hearing aid, (3) interaction between sound at the output of the hearing aid
      and the listener's ear, (4) integrity of the auditory system, (5) coding of
      available acoustic cues by the listener's auditory system, and (6) correct
      identification of the speech sound. Within this framework, this review describes
      methodology and research on 2 new assessment techniques: acoustic analysis of
      speech measured at the output of the hearing aid and auditory evoked potentials
      recorded while the listener wears hearing aids. Acoustic analysis topics include
      the relationship between conventional probe microphone tests and probe microphone
      measurements using speech, appropriate procedures for such tests, and assessment
      of signal-processing effects on speech acoustics and recognition. Auditory evoked
      potential topics include an overview of physiologic measures of speech processing
      and the effect of hearing loss and hearing aids on cortical auditory evoked
      potential measurements in response to speech. Finally, the clinical utility of
      these procedures is discussed.

PMID- 16959735
TI  - Effect of probe tube insertion depth on spectral measures of speech.
AB  - This study investigated how depth variations in the tip of the probe tube
      affected spectral measures of speech recorded in the external ear canal.
      Consonant-vowel nonsense syllables were recorded with a probe tube microphone
      system in 10 adult participants with normal middle ear function. Recordings were
      made with the probe tube tip placed 1 mm, 5 mm, and 10 mm beyond the medial tip
      of a custom earmold. The effect of probe depth was evaluated on spectral levels
      (one-third octave and one- twelfth octave band). Extending the probe tube 10 mm
      past the medial tip of the earmold gave the most accurate results, with
      relatively lower sound levels for either the 1-mm or 5-mm insertion depth. In
      general, the effect of insertion depth was minimal at frequencies below 3 to 4
      kHz, although this varied with the specific phoneme and the width of the analysis
      bands. The authors found no significant difference between 1- and 5-mm insertion
      depths, suggesting that as long as the tip of the probe tube is sufficiently
      close to the tympanic membrane to capture the highest frequency of interest, it
      makes little difference if it is less than 5 mm beyond the earmold tip.

PMID- 16959736
TI  - The neural representation of consonant-vowel transitions in adults who wear
      hearing AIDS.
AB  - Hearing aids help compensate for disorders of the ear by amplifying sound;
      however, their effectiveness also depends on the central auditory system's
      ability to represent and integrate spectral and temporal information delivered by
      the hearing aid. The authors report that the neural detection of time-varying
      acoustic cues contained in speech can be recorded in adult hearing aid users
      using the acoustic change complex (ACC). Seven adults (50-76 years) with mild to
      severe sensorineural hearing participated in the study. When presented with 2
      identifiable consonant-vowel (CV) syllables ("shee" and "see"), the neural
      detection of CV transitions (as indicated by the presence of a P1-N1-P2 response)
      was different for each speech sound. More specifically, the latency of the evoked
      neural response coincided in time with the onset of the vowel, similar to the
      latency patterns the authors previously reported in normal-hearing listeners.

PMID- 16959737
TI  - Perioperative CNS outcomes: management, metabolism, and monitoring. Proceedings
      of the Ninth Annual Outcomes Key West Symposium in May 2005, Key West, Florida,
      USA and the Cardiac Team Meeting in March 2005, Whistler, British Columbia,
      Canada.

PMID- 16959738
TI  - Neurologic complications in noncardiac surgery.
AB  - In this article, the incidence of nervous system injuries associated with
      noncardiac surgery is reviewed briefly. In general, these can be divided into
      injuries that are clinically apparent (eg, stroke or peripheral nerve damage),
      which may generally be detectable on clinical examination, and more subtle forms
      of brain injury (eg, personality changes and postoperative cognitive
      dysfunction), injuries that are primarily detected by neuropsychological testing.

PMID- 16959739
TI  - The blood-brain barrier and blood-cerebral spinal fluid barrier.
AB  - An intact blood-brain barrier and normal production, circulation, and absorption
      of cerebrospinal fluid are critical for normal brain function. Minor disruptions
      of barrier function are without clinical consequences. Major disruptions
      accompany most significant acute brain injuries. The anatomic location of the
      blood-brain barrier is the endothelial cells of arterioles, capillaries, veins,
      and the epithelial cell surface of the choroid plexus. However, endothelial cells
      require the presence of glial cells to maintain barrier function. During
      cardiopulmonary bypass, several factors may result in a temporary disruption of
      the barrier; the most important are systemic inflammatory response and focal
      ischemia due to emboli. Lacking a lymphatic system, the brain depends on the
      circulation of cerebrospinal fluid to remove the products of metabolism, and the
      circulation of cerebrospinal fluid depends on a vascular systolic pulse wave to
      drive this fluid antegrade along the brain paravascular spaces. Although it is
      not possible to identify this paravascular space histologically, its presence is
      confirmed by tracer methods.

PMID- 16959740
TI  - Aprotinin and the protease-activated receptor 1 thrombin receptor:
      antithrombosis, inflammation, and stroke reduction.
AB  - Cardiopulmonary bypass, although remaining an indispensable asset in cardiac
      surgery, especially in more complex and repeat operations, is associated with
      significant thrombin generation in the bypass circuit, leading to the activation
      of platelets, the coagulation system, an inflammatory response, and perioperative
      stroke. Recent clinical studies and meta-analyses of clinical trials in coronary
      artery bypass grafting surgery have confirmed that aprotinin not only reduces
      transfusion requirements in cardiac surgery but also confers significant
      protection against platelet dysfunction, activation of the systemic inflammatory
      response, and perioperative stroke when administered at the full (or
      "Hammersmith") dose. This article reviews research from several independent
      groups to propose a novel mechanism through which the antithrombotic, anti
      inflammatory, and neuroprotective mechanism might be mediated, via protection of
      the high-affinity thrombin receptor protease-activated receptor 1 (PAR1).

PMID- 16959741
TI  - Aortic arch atheroma: stroke reduction in cardiac surgical patients.
AB  - Cardiac surgery is increasingly performed on elderly patients with extensive
      coronary artery abnormalities who have impaired left ventricular function,
      decreased physiologic reserve, and multiple comorbid conditions. Considerable
      numbers of these patients develop perioperative neurologic complications ranging
      from subtle cognitive dysfunction to more evident postoperative confusion,
      delirium, and, less commonly, clinically apparent stroke. Magnetic resonance
      imaging studies have elucidated that a considerable number of patients have new
      ischemic brain infarcts, particularly after conventional coronary artery bypass
      graft surgery. Mechanisms of cerebral injury during and after cardiac surgery are
      discussed. Intraoperative transesophageal echocardiography and epiaortic scanning
      for detection of atheromatous disease of the proximal thoracic aorta is paramount
      in identifying patients at high risk from neurologic injury. It is important to
      recognize that our efforts to minimize neurologic injury should not be limited to
      the intraoperative period. Particular efforts should be directed to temperature
      management, glycemia control, and pharmacologic neuroprotection extending into
      the postoperative period. Preoperative magnetic resonance angiography may be of
      value for screening patients with significant atheroma of the proximal thoracic
      aorta. It is likely that for patients with no significant atheromatous disease,
      conventional coronary artery revascularization is the most effective long-term
      strategy, whereas patients with atheromatous thoracic aorta may be better managed
      with beating heart surgery, hybrid techniques, or medical therapy alone. Patient
      stratification based on the aortic atheromatic burden should be addressed in
      future trials designed to tailor treatment strategies to improve long-term
      outcomes of coronary heart disease and reduce the risks of perioperative
      neurologic injury.

PMID- 16959742
TI  - Aortic assessment for cardiac surgical procedures.
AB  - Aortic atheromatous disease is associated with stroke in both the ambulatory and
      perioperative setting. In addition to atheromatous deposits, a reduction in the
      compliance of the aorta takes place as elastin fibers are replaced by collagen
      fibers. Both of these distinct processes, termed atherosclerosis, can easily be
      measured using transesophageal echocardiography during cardiac surgery. A review
      of the literature demonstrates many studies supporting the benefit of
      transesophageal echocardiography examination of the aorta for reducing stroke
      following cardiac surgery, through modification of surgical techniques. There
      have also been attempts by surgeons to remove atheromatous lesions from the aorta
      during cardiac surgery. Unfortunately, these procedures currently have a high
      perioperative mortality. Finally, medical therapy such as warfarin or statins may
      help reduce the incidence of stroke following heart surgery.

PMID- 16959743
TI  - Transesophageal echocardiography in the intensive care unit.
AB  - Transesophageal echocardiography provides unique diagnostic capabilities,
      allowing for a very precise look at the structure and hemodynamics of the human
      heart. It is minimally invasive and portable, and quickly diagnoses sudden
      hemodynamic changes in intensive care patients. It provides invaluable and
      precise information about myocardial dysfunction and intracardiac volume status.
      It can diagnose dynamic left ventricular outflow obstruction, infrequent but
      serious complication of aortic valve replacement, septal myectomy, or mitral
      valve repair. Transesophageal echocardiography examination can exclude cardiac
      tamponade and intracardiac source of embolization, and it offers the ability to
      visualize native or prosthetic valves and assesses their function in the
      postoperative period. It is helpful in diagnosing endocarditis and the presence
      of intracardiac masses. In the diagnosis of blunt chest trauma, transesophageal
      echocardiography offers a fast and safe look at ascending and descending aorta
      and pericardial effusion, facilitating future decisions about patient management.
      In patients with postoperative hypoxia, it can exclude intracardiac shunt.
      Finally, in heart transplants or in managing patients with mechanical heart
      assist devices, transesophageal echocardiography is an invaluable tool in
      assessing progress of treatment and complications arising from the procedures.
      With the introduction of multiplane transesophageal echocardiography probes,
      technology, and experienced personnel, transesophageal echocardiography becomes
      the extension of the physical examination in the intensive care unit. This
      example is one of only a few whereby technology brings the physician closer to
      the patient.

PMID- 16959744
TI  - Beating heart versus conventional cardiopulmonary bypass: the octopus experience:
      a randomized comparison of 281 patients undergoing coronary artery bypass surgery
      with or without cardiopulmonary bypass.
AB  - In the Octopus Study, 281 coronary artery bypass surgery patients were randomized
      to surgery with or without cardiopulmonary bypass. The primary objective was to
      compare cognitive outcome between off-pump and on-pump coronary artery bypass
      surgery. Before and after surgery, psychologists administered a battery of 10
      neuropsychological tests to the patients. Cognitive decline was defined as a
      decrease in an individual's performance of at least 20% from baseline, in at
      least 20% of the main variables. According to this definition, cognitive decline
      was present in 21% in the off-pump group and 29% in the on-pump group, 3 months
      after the procedure (P = .15). At 12 months, cognitive decline was present in 31%
      in the off-pump group and 34% in the on-pump group (P = .69). These results
      indicated that patients undergoing coronary artery bypass surgery without
      cardiopulmonary bypass had improved cognitive outcomes 3 months after the
      procedure, but the effects were limited and became negligible at 12 months. The
      same definition of cognitive decline was also applied to 112 volunteers not
      undergoing surgery. The definition labeled 28% of the control subjects as
      suffering from cognitive decline, 3 months after their first assessment. This
      suggests that the natural fluctuations in performance during repeated
      neuropsychological testing should be included in the statistical analysis of
      cognitive decline. Using an alternative definition of cognitive decline that
      takes these natural fluctuations in performance into account, the proportions of
      coronary artery bypass surgery patients displaying cognitive decline were
      substantially lower. This indicates that the incidence of cognitive decline after
      coronary artery bypass surgery has been overestimated.

PMID- 16959745
TI  - Outcome improvement and cost reduction in an increasingly morbid cardiac surgery
      population.
AB  - Two studies assessed initiatives to improve the quality and the cost
      effectiveness of cardiac surgery. The first evaluated a system for access and
      stabilization (SAS), with coronary stabilization, and a clinical effectiveness
      quality initiative (CEQI) in off-pump coronary artery bypass grafting. The SAS +
      CEQI cohort showed significantly lower mortality, a lower percentage of patients
      requiring prolonged ventilation, and a shorter mean postoperative length of
      hospital stay than the pre-SAS cohort who underwent on-pump coronary artery
      bypass grafting. The second study assessed the potential for noninvasive cerebral
      oximetry to reduce strokes related to all cardiac surgery by optimizing cerebral
      oxygen delivery. The incidence of permanent stroke was significantly lower in the
      cerebral oximetry group than in an earlier control group in which cerebral
      oximetry was not used, despite the fact that the study group had a significantly
      greater number of patients in New York Heart Association classes III and IV. The
      proportion of patients requiring prolonged ventilation was significantly lower,
      and the length of postoperative hospital stay was significantly shorter in the
      study group than in the control group. The incidence of cerebrovascular accident
      in the study group was 0.97%, compared with 2.03% in the controls. This
      translated to a potential avoidance of 12 cerebrovascular accidents and
      approximately $254,214 in direct costs and more than $425,000 in total costs. The
      results show that specific measures can improve outcomes and reduce costs in
      cardiac surgery. Therefore, the use of a clinical effectiveness quality
      initiative and cerebral oximetry in all cardiac surgery, with the SAS system for
      off-pump surgery, should be advocated.

PMID- 16959746
TI  - Hemostasis and glycemic control in the cardiac surgical patient.
AB  - The Centers for Disease Control and Prevention estimate that 6% of the US
      population meets diagnostic criteria for diabetes mellitus, with at least one
      third of this group being undiagnosed. A majority of adult blindness, renal
      insufficiency, and limb amputation may be directly attributed to diabetes.
      Although the incidence of type 1, autoimmune-mediated diabetes remains relatively
      stable, increasing age, physical inactivity, and obesity have produced explosive
      growth in insulin resistance and type 2 diabetes. A direct association between
      diabetes and atherothrombotic disease remains indisputable. However, recent data
      further suggest that even minor elevations of fasting plasma glucose, in
      "nondiabetic" subjects, increase cardiovascular risk. Alterations in hemostasis
      may play an important contributory role. Both hyperglycemia and hyperinsulinemia
      induce prothrombotic characteristics, including overexpression of vascular
      endothelial plasminogen activator inhibitor-1 (PAI-1), down-regulation of
      fibrinolysis, elevation of plasma coagulation proteins (ie, fibrinogen, factor
      VII, factor X), and enhanced platelet activation. Furthermore, endothelial
      dysfunction-characterized by an inflammatory phenotype-commonly accompanies
      diabetes. Given data supporting prothrombotic potential of both acute and chronic
      hyperglycemia, aggressive perioperative glucose control appears imperative.

PMID- 16959747
TI  - Management of high-risk perioperative systems.
AB  - The perioperative system is a complex system that requires people, materials, and
      processes to come together in a highly ordered and timely manner. However, when
      working in this high-risk system, even well-organized, knowledgeable, vigilant,
      and well-intentioned individuals will eventually make errors. All systems need to
      be evaluated on a continual basis to reduce the risk of errors, make errors more
      easily recognizable, and provide methods for error mitigation. A simple approach
      to risk management that may be applied in clinical medicine is discussed.

PMID- 16959748
TI  - Angiogenesis for the treatment of inoperable coronary disease: the future.
AB  - Improved treatment options and better management of cardiovascular risk factors
      have resulted in improved outcomes for patients suffering from severe coronary
      artery disease. However, coronary artery disease may be of such a diffuse and
      severe manner that repeated attempts at catheter-based interventions and coronary
      artery bypass grafting may be unsuccessful at restoring normal myocardial blood
      flow. It is the goal of therapeutic angiogenesis to restore perfusion to
      chronically ischemic myocardium using protein growth factors, gene therapy, or,
      more recently, cell-based therapy, without intervening on the epicardial coronary
      arteries. However, angiogenesis has not yet provided significant clinical benefit
      and is still reserved as an experimental treatment for patients who have failed
      conventional therapies. Once potential endogenous inhibitors of vascular
      development can be modified, angiogenesis may become more useful for therapeutic
      purposes. It is hoped that angiogenesis for therapeutic purposes will one day
      effectively re-create the potent natural processes of vascularization that every
      human being undergoes during growth and development and become a major modality
      for the treatment of coronary artery disease.

PMID- 16959750
TI  - Hypertension and the heart.
AB  - The interactions linking high blood pressure with hypertensive heart disease are
      reciprocal. Hypertension can be regarded as a source of adverse effects on
      myocardial structure and function by favoring the development and progression of
      left ventricular hypertrophy and of left ventricular dysfunction and failure in
      the advanced phases of the disease. Conversely, the heart can be regarded as a
      source of reflex influences on the cardiovascular system, which appear to be
      deranged in the hypertensive state. The clinical relevance of this reflex
      dysfunction is based on the evidence that these alterations may favor the
      occurrence of an increased sympathetic vasoconstrictor drive, thereby promoting
      the development of the1 hypertensive state. Both phenomena have important clinic
      and therapeutic implications potentiating the cardiovascular risk profile of the
      hypertensive patient.

PMID- 16959751
TI  - Systolic hypertension in elderly patients.
AB  - Pulsatile arterial hemodynamics in cardiovascular diseases indicate that the
      aortic blood pressure curve may be represented by 2 different phenotypes: one in
      patients 64 years old and younger and the other in subjects older than 65 years.
      The 2 blood pressure curves may have exactly the same mean arterial pressure (ie,
      the same cross-sectional area under the curve) but quite different shapes. In
      older subjects, systolic blood pressure and pulse pressure are higher, whereas
      diastolic blood pressure is lower than in younger subjects.

PMID- 16959752
TI  - Background and treatment of metabolic syndrome: a therapeutic challenge.
AB  - Metabolic syndrome is characterized by a clustering of cardiovascular and
      metabolic risk factors. This syndrome is now widely recognized as a distinct
      pathologic entity. It is receiving a great deal of attention in the medical
      literature and also in the lay press. People with metabolic syndrome have a
      clustering of the following risk factors, including detrimental changes in
      glucose tolerance and insulin resistance, abdominal (visceral) obesity,
      atherogenic dyslipidemia, and hypertension. Metabolic syndrome is associated with
      important cardiovascular and cerebrovascular and metabolic risks. Prevention and
      treatment are therefore of great importance. Preventive measures involving
      lifestyle are mandatory. In addition, metabolic syndrome patients will require
      pharmacologic treatment, usually for the rest of their lives. Complex patterns of
      drug treatment are required. This review provides an extensive and critical
      review of the drug treatment of this complex pathologic entity.

PMID- 16959753
TI  - Acute insulin resistance in myocardial ischemia: causes and consequences.
AB  - Diabetes mellitus is associated with increased risk for cardiovascular mortality
      because of multiple pathophysiologic mechanisms. Acute stress-induced hyper
      glycemia during acute myocardial infarction has gained much attention, as blood
      glucose levels seem to be an independent risk factor for acute myocardial
      infarction-related death. Clinical studies that identify stress-induced
      hyperglycemia as a risk factor are reviewed and its causes are discussed. They
      can be summarized as the consequence of acute insulin resistance, which in its
      turn is caused by stress hormones and by proinflammatory cytokines. Hyperglycemia
      causes the release of proinflammatory cytokines, the induction of reactive
      radicals, alterations in cardiovascular substrate metabolism, and propagation of
      coagulation and apoptosis. These all have harmful effects during and after acute
      myocardial infarction. Recommendations are for strict glycemic control in
      hyperglycemic patients with acute myocardial infarction, although the target
      glucose level is still a subject of debate.

PMID- 16959754
TI  - Hyperglycemia and outcome after myocardial infarction and cardiac surgery: so
      what?
AB  - Hyperglycemia is a frequent observation during acute illness such as myocardial
      infarction and after major surgery. The proportion of patients with hyperglycemia
      may be as high as 95% to 100% after cardiac surgery. This stress-induced
      hyperglycemia has a detrimental effect on outcome after myocardial infarction and
      cardiac surgery. Mortality may increase by a factor of 4, especially in non
      diabetic patients. Control of hyperglycemia to normalize blood glucose is
      associated with a clear clinical benefit. This effect is most beneficial in
      nondiabetic patients with hyperglycemia. The exact target level of glycemia is
      still a matter of investigation, but normalization to values between 80 and 125
      mg/dL is probably optimal.

PMID- 16959755
TI  - Glucose-insulin-potassium techniques in cardiac surgery: historical overview and
      future perspectives.
AB  - Since the days of the first cardiac surgical operations in the previous century,
      myocardial preservation has been an essential component of the successful outcome
      of these procedures. Although many different techniques to achieve myocardial
      preservation and modulation have been described in the past 50 years, this review
      focuses on the use of glucose, insulin, and potassium (GIK) and its effect on
      ischemic and postischemic myocardium.

PMID- 16959756
TI  - Optimizing cardiac fatty acid and glucose metabolism as an approach to treating
      heart failure.
AB  - Despite the recent introduction of new therapeutic approaches to treat heart
      failure, mortality from heart failure remains high, and patients still frequently
      experience progression of contractile dysfunction and ongoing left ventricular
      enlargement. Therefore, new treatments are needed for heart failure that work
      independently of mechanisms already targeted. Emerging evidence suggests that the
      failure of the myocardium in heart failure is affected by alterations in the
      energy substrate metabolism. In particular, there is now evidence that in the
      failing heart, shifting metabolism away from a preference for fatty acids toward
      more carbohydrate oxidation can improve contractile function and slow the
      progression of pump failure.

PMID- 16959757
TI  - Free Fatty acids and postischemic myocardial function.
AB  - This review highlights the changes in fatty acid homeostasis in the postischemic
      heart. The impact of restoration of flow (reperfusion) after an ischemic episode
      on both structural fatty acids (ie, incorporated in phospholipids, the building
      blocks of cellular membranes) and fatty acids, serving as energy donors by
      mitochondrial oxidation, are discussed. Attempts to interfere with cardiac fatty
      acid homeostasis to prevent loss of cardiac function or to restore cardiac
      performance after reperfusion is also discussed.

PMID- 16959758
TI  - Early reperfusion phenomena.
AB  - Cycles of ischemia-reperfusion are ubiquitous in clinical cardiology. Depending
      on the duration and intensity of the ischemic episode as well as its repetition
      mode, several pathophysiologic syndromes have been identified, such as myocardial
      stunning, hibernation, and preconditioning. It remains a difficult exercise to
      distinguish ischemic from reperfusion damage. Production of oxygen free radicals
      and alteration in calcium homeostasis are major players during early reperfusion,
      responsible for the pathologic and functional alterations. At the molecular
      level, upregulation and downregulation of a number of genes have been observed in
      stunned myocardium, pointing toward some inborn survival adaptive mechanism. The
      no-reflow phenomenon, a most paradoxic event after reperfusion, usually occurs
      after more prolonged episodes of ischemia. The underlying mechanism involves
      additional lesions to the microvasculature interacting with myocytes lesions.
      Further insight into molecular and genomic adaptation to ischemia and reperfusion
      will undoubtedly help to improve our ability to fight reperfusion injury.

PMID- 16959759
TI  - A commentary on clinical trials in chronic heart failure.
AB  - Heart failure is a common condition and becoming more common. Many treatments
      have been evaluated in large clinical trials during the last few decades. These
      trials can be criticized but do provide an evidence base for treatment, probably
      greater than for most other clinical conditions. Weaknesses exist in relation to
      age, ejection fraction, and gender. Most trials have included patients 10 years
      younger than those in the general population. There is little evidence for
      efficacy in patients with a near normal ejection fraction. Few women have been
      included in trials.

PMID- 16959760
TI  - An overview of inotropic agents.
AB  - The use of inotropic agents has been surrounded by many controversies. Recent
      guidelines for the treatment of patients with chronic and acute heart failure
      have elucidated some of the issues, but many remain. As a result, a substantial
      variability in the use of agents between institutions and caregivers remains,
      which mainly results from the lack of uniform data in the literature. Prospective
      randomized trials with a long-term follow-up and sufficient power are clearly
      needed, and a number of trials are currently in progress.

PMID- 16959761
TI  - REMATCH and beyond: the cost of treating heart failure using an implantable left
      ventricular assist device.
AB  - Congestive heart failure is an increasingly widespread debilitating fatal
      condition that generates a high cost to patients, society, and health care
      systems. Nearly 6.5 million people in Europe and 5 million people in the United
      States have congestive heart failure. Unlike most cardiovascular diseases in
      industrialized countries, congestive heart failure is becoming more common.
      Therapies include medical approaches, implantable assist devices, and cardiac
      transplantation. Mechanical assistance devices rather than medical therapy offer
      improvement in quality of life and survival.

PMID- 16959762
TI  - Sex, the heart, and heart failure.
AB  - In the modern era of pharmacologic treatment of erectile dysfunction, men with
      heart disease increasingly approach their physicians regarding the possibility of
      restoring sexual activity. At the same time, patients are also frequently aware
      of public figures that have reportedly died during coitus, often in the arms of
      their mistresses or prostitutes. Added to this is the perception of patients, and
      oftentimes their physicians, that coitus and orgasm are associated with a near
      maximal or even "supermaximal" cardiac workload and therefore may be hazardous
      for a diseased heart. Accordingly, knowledge of the cardiovascular effects of
      sexual activity, the risks of triggering a cardiovascular event, and the
      potential risks inherent in the use of drug therapy of male impotence is
      important to properly advise patients and their spouses regarding this sensitive
      issue.

PMID- 16959763
TI  - Transgenic mouse proteomics identifies new 14-3-3-associated proteins involved in
      cytoskeletal rearrangements and cell signaling.
AB  - Identification of protein-protein interactions is crucial for unraveling cellular
      processes and biochemical mechanisms of signal transduction. Here we describe,
      for the first time, the application of the tandem affinity purification (TAP) and
      LC-MS method to the characterization of protein complexes from transgenic mice.
      The TAP strategy developed in transgenic mice allows the emplacement of complexes
      in their physiological environment in contact with proteins that might only be
      specifically expressed in certain tissues while simultaneously ensuring the right
      stoichiometry of the TAP protein versus their binding partners and represents a
      novelty in proteomics approaches used so far. Mouse lines expressing TAP-tagged
      14-3-3zeta protein were generated, and protein interactions were determined. 14-3
      3 proteins are general regulators of cell signaling and represent up to 1% of the
      total brain protein. This study allowed the identification of almost 40 novel 14
      3-3zeta-binding proteins. Biochemical and functional characterization of some of
      these interactions revealed new mechanisms of action of 14-3-3zeta in several
      signaling pathways, such as glutamate receptor signaling via binding to homer
      homolog 3 (Homer 3) and in cytoskeletal rearrangements and spine morphogenesis by
      binding and regulating the activity of the signaling complex formed by G protein
      coupled receptor kinase-interactor 1 (GIT1) and p21-activated kinase-interacting
      exchange factor beta (betaPIX).

PMID- 16959764
TI  - Regulation of FNR dimerization by subunit charge repulsion.
AB  - Dimerization of the global anaerobic transcription factor FNR is essential for
      FNR activity. Under aerobic conditions FNR is an inactive monomeric species
      because it lacks the oxygen labile [4Fe-4S] cluster required for dimerization. In
      this study, we investigated the protein side chains that inhibit FNR dimerization
      under aerobic conditions. Substitution of Asp(154) within the predicted
      dimerization helix with residues containing neutral or positively charged side
      chains increased FNR activity under aerobic conditions, whereas replacement of
      Asp(154) with Glu inhibited FNR activity similar to WT-FNR. Similar results were
      obtained when making analogous substitutions of Glu(150). In vitro analysis of
      representative FNR mutant proteins indicated that their increased activity under
      aerobic conditions resulted from an [4Fe-4S] independent mechanism of
      dimerization. In addition, simultaneous substitution of residues 150 and 154 with
      Lys restored inhibition of FNR activity under aerobic growth conditions.
      Collectively, these data indicate that charge repulsion by side chains at
      positions 150 and 154 is necessary to inhibit dimerization under aerobic
      conditions. They also suggest that a [4Fe-4S]-dependent conformational change
      overcomes charge repulsion between subunits under anaerobic conditions.
      Comparison of the trypsin sensitivity of [4Fe-4S]-FNR and apoFNR indicated that
      there are no major differences in protease sensitivity between these forms,
      whereas circular dichroism suggested that small changes in secondary structure
      occur between the cluster-containing FNR and apoFNR. Thus, the [4Fe-4S]-dependent
      conformational change necessary to overcome inter-subunit charge repulsion and
      create a subunit interface more favorable for dimerization must be small.

PMID- 16959765
TI  - N-glycosylation of the beta-propeller domain of the integrin alpha5 subunit is
      essential for alpha5beta1 heterodimerization, expression on the cell surface, and
      its biological function.
AB  - The N-glycosylation of integrin alpha5beta1 is thought to play crucial roles in
      cell spreading, cell migration, ligand binding, and dimer formation, but the
      underlying mechanism remains unclear. To investigate the importance of the N
      glycans of this integrin in detail, sequential site-directed mutagenesis was
      carried out to remove single or combined putative N-glycosylation sites on the
      alpha5 integrin. Removal of the putative N-glycosylation sites on the beta
      propeller, Thigh, Calf-1, or Calf-2 domains of the alpha5 subunit resulted in a
      decrease in molecular weight compared with the wild type, suggesting that all of
      these domains contain attached N-glycans. Importantly, the absence of N
      glycosylation sites (sites 1-5) on the beta-propeller resulted in the persistent
      association of integrin subunit with calnexin in the endoplasmic reticulum, which
      subsequently blocked heterodimerization and its expression on the cell surface.
      Interestingly, the activities for cell spreading and migration for the alpha5
      subunit carrying only three potential N-glycosylation sites (3-5 sites) on the
      beta-propeller were comparable with those of the wild type. In contrast, mutation
      of these three sites resulted in a significant decrease in cell spreading as well
      as functional expression, although the total expression level of the Delta3-5
      mutant on the cell surface was comparable with that of wild type. Furthermore, we
      found that site 5 is a most important site for its expression on the cell
      surface, whereas the S5 mutant did not show any biological functions. Taken
      together, this study reveals for the first time that the N-glycosylation on the
      beta-propeller domain of the alpha5 subunit is essential for heterodimerization
      and biological functions of alpha5beta1 integrin and might also be useful for
      studies of the molecular structure.

PMID- 16959766
TI  - Conditional deletion of Shp2 in the mammary gland leads to impaired lobulo
      alveolar outgrowth and attenuated Stat5 activation.
AB  - Stat5 and Stat3, two members of the Stat (signal transducer and activator of
      transcription) family, are known to play critical roles in
      mammopoiesis/lactogenesis and involution, respectively, in the mammary gland.
      Phosphotyrosine phosphatase Shp2 has been shown to dephosphorylate and thus
      inactivate both Stat5 and Stat3 in vitro. Paradoxically, cell culture studies
      also suggest a positive role of Shp2 in promoting prolactin-stimulated Stat5
      activation. We have shown here that selective deletion of Shp2 in mouse mammary
      glands suppresses Stat5 activity during pregnancy and lactation, resulting in
      significant impairment of lobulo-alveolar outgrowth and lactation. In contrast,
      Stat3 activity was slightly up-regulated shortly before/at involution, leading to
      normal epithelial cell apoptosis/involution in Shp2-deficient mammary gland.
      Thus, Shp2 acts to promote Stat5 activation by the JAK2.prolactin receptor
      complex, while negatively modulating Stat3 activity before the onset of
      involution. This is the first demonstration that Shp2 manipulates Stat5 and Stat3
      activities reciprocally in mammary epithelial cells, providing novel insight into
      the complex mechanisms for regulation of various Stat family members by a
      cytoplasmic tyrosine phosphatase.

PMID- 16959767
TI  - A crucial role for matrix metalloproteinase 2 in osteocytic canalicular formation
      and bone metabolism.
AB  - Extracellular matrix production and degradation by bone cells are critical steps
      in bone metabolism. Mutations of the gene encoding MMP-2, an extracellular matrix
      degrading enzyme, are associated with a human genetic disorder characterized by
      subcutaneous nodules, arthropathy, and focal osteolysis. It is not known how the
      loss of MMP-2 function results in the pathology. Here, we show that Mmp2(-/-)
      mice exhibited opposing bone phenotypes caused by an impaired osteocytic
      canalicular network. Mmp2(-/-) mice showed decreased bone mineral density in the
      limb and trunk bones but increased bone volume in the calvariae. In the long
      bones, there was moderate disruption of the osteocytic networks and reduced bone
      density throughout life, whereas osteoblast and osteoclast function was normal.
      In contrast, aged but not young Mmp2(-/-) mice had calvarial sclerosis with
      osteocyte death. Severe disruption of the osteocytic networks preceded osteocyte
      loss in Mmp2(-/-) calvariae. Successful transplantation of wild-type periosteum
      restored the osteocytic canalicular networks in the Mmp2(-/-) calvariae,
      suggesting local roles of MMP-2 in determining bone phenotypes. Our results
      indicate that MMP-2 plays a crucial role in forming and maintaining the
      osteocytic canalicular network, and we propose that osteocytic network formation
      is a determinant of bone remodeling and mineralization.

PMID- 16959768
TI  - Smad4-dependent regulation of urokinase plasminogen activator secretion and RNA
      stability associated with invasiveness by autocrine and paracrine transforming
      growth factor-beta.
AB  - Metastasis is a primary cause of mortality due to cancer. Early metastatic growth
      involves both a remodeling of the extracellular matrix surrounding tumors and
      invasion of tumors across the basement membrane. Up-regulation of extracellular
      matrix degrading proteases such as urokinase plasminogen activator (uPA) and
      matrix metalloproteinases has been reported to facilitate tumor cell invasion.
      Autocrine transforming growth factor-beta (TGF-beta) signaling may play an
      important role in cancer cell invasion and metastasis; however, the underlying
      mechanisms remain unclear. In the present study, we report that autocrine TGF
      beta supports cancer cell invasion by maintaining uPA levels through protein
      secretion. Interestingly, treatment of paracrine/exogenous TGF-beta at higher
      concentrations than autocrine TGF-beta further enhanced uPA expression and cell
      invasion. The enhanced uPA expression by exogenous TGF-beta is a result of
      increased uPA mRNA expression due to RNA stabilization. We observed that both
      autocrine and paracrine TGF-beta-mediated regulation of uPA levels was lost upon
      depletion of Smad4 protein by RNA interference. Thus, through the Smad pathway,
      autocrine TGF-beta maintains uPA expression through facilitated protein
      secretion, thereby supporting tumor cell invasiveness, whereas exogenous TGF-beta
      further enhances uPA expression through mRNA stabilization leading to even
      greater invasiveness of the cancer cells.

PMID- 16959769
TI  - Protein repair in the brain, proteomic analysis of endogenous substrates for
      protein L-isoaspartyl methyltransferase in mouse brain.
AB  - Protein L-isoaspartyl methyltransferase (PIMT) catalyzes repair of L-isoaspartyl
      peptide bonds, a major source of protein damage under physiological conditions.
      PIMT knock-out (KO) mice exhibit brain enlargement and fatal epileptic seizures.
      All organs accumulate isoaspartyl proteins, but only the brain manifests an overt
      pathology. To further explore the role of PIMT in brain function, we undertook a
      global analysis of endogenous substrates for PIMT in mouse brain. Extracts from
      PIMT-KO mice were subjected to two-dimensional gel electrophoresis and blotted
      onto membranes. Isoaspartyl proteins were radiolabeled on-blot using [methyl
      (3)H]S-adenosyl-L-methionine and recombinant PIMT. Fluorography of the blot
      revealed 30-35 (3)H-labeled proteins, 22 of which were identified by peptide mass
      fingerprinting. These isoaspartate-prone proteins represent a wide range of
      cellular functions, including neuronal development, synaptic transmission,
      cytoskeletal structure and dynamics, energy metabolism, nitrogen metabolism, pH
      homeostasis, and protein folding. The following five proteins, all of which are
      rich in neurons, accumulated exceptional levels of isoaspartate: collapsin
      response mediator protein 2 (CRMP2/ULIP2/DRP-2), dynamin 1, synapsin I, synapsin
      II, and tubulin. Several of the proteins identified here are prone to age
      dependent oxidation in vivo, and many have been identified as autoimmune
      antigens, of particular interest because isoaspartate can greatly enhance the
      antigenicity of self-peptides. We propose that the PIMT-KO phenotype results from
      the cumulative effect of isoaspartate-related damage to a number of the neuron
      rich proteins detected in this study. Further study of the isoaspartate-prone
      proteins identified here may help elucidate the molecular basis of one or more
      developmental and/or age-related neurological diseases.

PMID- 16959770
TI  - Functional characterization of PmHS1, a Pasteurella multocida heparosan synthase.
AB  - Heparosan synthase 1 (PmHS1) from Pasteurella multocida Type D is a dual action
      glycosyltransferase enzyme that transfers monosaccharide units from uridine
      diphospho (UDP) sugar precursors to form the polysaccharide heparosan (N
      acetylheparosan), which is composed of alternating (-alpha4-GlcNAc-beta1,4-GlcUA
      1-) repeats. We have used molecular genetic means to remove regions nonessential
      for catalytic activity from the amino- and the carboxyl-terminal regions as well
      as characterized the functional regions involved in GlcUA-transferase activity
      and in GlcNAc-transferase activity. Mutation of either one of the two regions
      containing aspartate-X-aspartate (DXD) residue-containing motifs resulted in
      complete or substantial loss of heparosan polymerizing activity. However, certain
      mutant proteins retained only GlcUA-transferase activity while some constructs
      possessed only GlcNAc-transferase activity. Therefore, it appears that the PmHS1
      polypeptide is composed of two types of glycosyltransferases in a single
      polypeptide as was found for the Pasteurella multocida Type A PmHAS, the
      hyaluronan synthase that makes the alternating (-beta3-GlcNAc-beta1,4-GlcUA-1-)
      polymer. However, there is low amino acid similarity between the PmHAS and PmHS1
      enzymes, and the relative placement of the GlcUA-transferase and GlcNAc
      transferase domains within the two polypeptides is reversed. Even though the
      monosaccharide compositions of hyaluronan and heparosan are identical, such
      differences in the sequences of the catalysts are expected because the PmHAS
      employs only inverting sugar transfer mechanisms whereas PmHS1 requires both
      retaining and inverting mechanisms.

PMID- 16959771
TI  - Monoubiquitination of proliferating cell nuclear antigen induced by stalled
      replication requires uncoupling of DNA polymerase and mini-chromosome maintenance
      helicase activities.
AB  - Proliferating cell nuclear antigen (PCNA) is a homotrimeric, ring-shaped protein
      complex that functions as a processivity factor for DNA polymerases. Following
      genotoxic stress, PCNA is modified at a conserved site by either a single
      ubiquitin moiety or a polyubiquitin chain. These modifications are required to
      coordinate DNA damage tolerance processes with ongoing replication. The molecular
      mechanisms responsible for inducing PCNA ubiquitination are not well understood.
      Using Xenopus egg extracts, we show that ultraviolet radiation and aphidicolin
      treatment induce the mono- and diubiquitination of PCNA. PCNA ubiquitination is
      replication-dependent and coincides with activation of the ataxia telangiectasia
      mutated and Rad3-related (ATR)-dependent DNA damage checkpoint pathway. However,
      loss of ATR signaling by depletion of the ATR-interacting protein (ATRIP) or
      Rad1, a component of the 911 checkpoint clamp, does not impair PCNA
      ubiquitination. Primed single-stranded DNA generated by uncoupling of mini
      chromosome maintenance helicase and DNA polymerase activities has been shown
      previously to be necessary for ATR activation. Here we show that PCNA
      ubiquitination also requires uncoupling of helicase and polymerase activities. We
      further demonstrate that replicating single-stranded DNA, which mimics the
      structure produced upon uncoupling, is sufficient to induce PCNA
      monoubiquitination. Our results suggest that PCNA ubiquitination and ATR
      activation are two independent events that occur in response to a common single
      stranded DNA intermediate generated by functional uncoupling of mini-chromosome
      maintenance (MCM) helicase and DNA polymerase activities.

PMID- 16959772
TI  - Dyrk1A phosphorylates alpha-synuclein and enhances intracellular inclusion
      formation.
AB  - Lewy bodies (LBs) are pathological hallmarks of Parkinson disease (PD) but also
      occur in Alzheimer disease (AD) and dementia of LBs. Alpha-synuclein, the major
      component of LBs, is observed in the brain of Down syndrome (DS) patients with
      AD. Dyrk1A, a dual specificity tyrosine-regulated kinase (Dyrk) family member, is
      the mammalian ortholog of the Drosophila minibrain (Mnb) gene, essential for
      normal postembryonic neurogenesis. The Dyrk1A gene resides in the human
      chromosome 21q22.2 region, which is associated with DS anomalies, including
      mental retardation. In this study, we examined whether Dyrk1A interacts with
      alpha-synuclein and subsequently affects intracellular alpha-synuclein inclusion
      formation in immortalized hippocampal neuronal (H19-7) cells. Dyrk1A selectively
      binds to alpha-synuclein in transformed and primary neuronal cells. Alpha
      synuclein overexpression, followed by basic fibroblast growth factor-induced
      neuronal differentiation, resulted in cell death. We observed that accompanying
      cell death was increased alpha-synuclein phosphorylation and intracytoplasmic
      aggregation. In addition, the transfection of kinase-inactive Dyrk1A or Dyrk1A
      small interfering RNA blocked alpha-synuclein phosphorylation and aggregate
      formation. In vitro kinase assay of anti-Dyrk1A immunocomplexes demonstrated that
      Dyrk1A could phosphorylate alpha-synuclein at Ser-87. Furthermore, aggregates
      formed by phosphorylated alpha-synuclein have a distinct morphology and are more
      neurotoxic compared with aggregates composed of unmodified wild type alpha
      synuclein. These findings suggest alpha-synuclein inclusion formation regulated
      by Dyrk1A, potentially affecting neuronal cell viability.

PMID- 16959773
TI  - Real-time and single fibril observation of the formation of amyloid beta
      spherulitic structures.
AB  - In Alzheimer disease, amyloid beta, a 39-43-residue peptide produced by cleavage
      from a large amyloid precursor protein, undergoes conformational change to form
      amyloid fibrils and deposits as senile amyloid plaques in the extracellular
      cerebral cortices of the brain. However, the mechanism of how the intrinsically
      linear amyloid fibrils form spherical senile plaques is unknown. With total
      internal reflection fluorescence microscopy combined with the use of thioflavin
      T, an amyloid-specific fluorescence dye, we succeeded in observing the formation
      of the senile plaque-like spherulitic structures with diameters of around 15
      microm on the chemically modified quartz surface. Real-time observation at a
      single fibrillar level revealed that, in the absence of tight contact with the
      surface, the cooperative and radial growth of amyloid fibrils from the core leads
      to a huge spherulitic structure. The results suggest the underlying
      physicochemical mechanism of senile plaque formation, essential for obtaining
      insight into prevention of Alzheimer disease.

PMID- 16959774
TI  - Phosphorylation-independent ubiquitylation and endocytosis of Fc gammaRIIA.
AB  - Endocytosis of the Fc receptor Fc gammaRIIA depends on a functional ubiquitin
      conjugation system, and the receptor becomes ubiquitylated upon ligand binding.
      Phosphorylation of tyrosines in Fc gammaRIIA by Src family kinases is thought to
      be the initiating event in its signaling. However, although the Src family kinase
      inhibitor PP1 inhibited both ligand-induced phosphorylation of Fc gammaRIIA and
      phagocytosis in ts20 cells expressing Fc gammaRIIA, it did not inhibit receptor
      ubiquitylation or endocytosis of soluble ligands. Conversely, genistein and the
      proteasomal inhibitor MG132 did not inhibit receptor phosphorylation but strongly
      inhibited both receptor ubiquitylation and endocytosis. A region of the receptor
      lying within the immunoreceptor tyrosine-based activation motif was found to be
      necessary for both ubiquitylation and endocytosis. Ubiquitylation occurs at the
      plasma membrane before internalization. Endocytosis of Fc gammaRIIA is dependent
      on clathrin but independent of the adaptor protein AP-2. These findings point to
      a novel mechanism for ubiquitylation and endocytosis of this immunoreceptor.

PMID- 16959775
TI  - Mechanistic analysis of a DNA end processing pathway mediated by the Xenopus
      Werner syndrome protein.
AB  - The first step of homology-dependent repair of DNA double-strand breaks is the
      strand-specific processing of DNA ends to generate 3' single-strand tails.
      Despite its importance, the molecular mechanism underlying end processing is
      poorly understood in eukaryotic cells. We have taken a biochemical approach to
      investigate DNA end processing in nucleoplasmic extracts derived from the
      unfertilized eggs of Xenopus laevis. We found that double-strand DNA ends are
      specifically degraded in the 5' --> 3' direction in this system. The reaction
      consists of two steps: an ATP-dependent unwinding of double-strand ends and an
      ATP-independent 5' --> 3' degradation of single-strand tails. We also found that
      the Xenopus Werner syndrome protein, a member of the RecQ helicase family, plays
      an important role in DNA end processing. Mechanistically, Xenopus Werner syndrome
      protein (xWRN) is required for the unwinding of DNA ends but not for the
      degradation of single-strand tails. The xWRN-mediated end processing is
      remarkably similar to the end processing that has been proposed for the
      Escherichia coli RecQ helicase and RecJ single-strand nuclease, suggesting that
      this mechanism might be conserved in prokaryotes and eukaryotes.

PMID- 16959776
TI  - Seven transmembrane receptor core signaling complexes are assembled prior to
      plasma membrane trafficking.
AB  - Much is known about beta2-adrenergic receptor trafficking and internalization
      following prolonged agonist stimulation. However, less is known about outward
      trafficking of the beta2-adrenergic receptor to the plasma membrane or the role
      that trafficking might play in the assembly of receptor signaling complexes,
      important for targeting, specificity, and rapidity of subsequent signaling
      events. Here, by using a combination of bioluminescence resonance energy
      transfer, bimolecular fluorescence complementation, and confocal microscopy, we
      evaluated the steps in the formation of the core receptor-G protein heterotrimer
      complex. By using dominant negative Rab and Sar GTPase constructs, we demonstrate
      that receptor dimers and receptor-G betagamma complexes initially associate in
      the endoplasmic reticulum, whereas G alpha subunits are added to the complex
      during endoplasmic reticulum-Golgi transit. We also observed that G protein
      heterotrimers adopt different trafficking itineraries when expressed alone or
      with stoichiometric co-expression with receptor. Furthermore, deliberate
      mistargeting of specific components of these complexes leads to diversion of
      other members from their normal subcellular localization, confirming the role of
      these early interactions in targeting and formation of specific signaling
      complexes.

PMID- 16959777
TI  - The 2'-phosphate of NADP is responsible for proper orientation of the
      nicotinamide ring in the oxidative decarboxylation reaction catalyzed by sheep
      liver 6-phosphogluconate dehydrogenase.
AB  - Sheep liver 6-phosphogluconate dehydrogenase shows a high specificity for NADP,
      with a much lower affinity for NAD. Discrimination between NADP and NAD suggests
      that the interactions between the 2'-phosphate and 6-phosphogluconate
      dehydrogenase contribute most of the binding energy for NADP. There are three
      active site residues, Asn-32, Arg-33, and Thr-34, that hydrogen-bond to the 2'
      phosphate of NADP according to the crystal structure of the E.Nbr(8)ADP complex.
      In this study alanine mutagenesis was used to probe the contribution of each of
      the three residues to binding the cofactor and to catalysis. All mutant enzymes
      exhibit no significant change in V/E(t) or K(6PG) but an increase in K(NADP) that
      ranges from 6- to 80-fold. All mutant enzymes also exhibit at least a 7-fold
      increase in the primary kinetic (13)C-isotope effect-1, indicating that the
      decarboxylation step has become more rate-limiting. Data are consistent with
      significant roles for Asn-32, Arg-33, and Thr-34 in providing binding energy for
      NADP, and more importantly, the 2'-phosphate of NADP is required for proper
      orientation of the cofactor to allow rotation about the N-glycosidic bond as it
      is reduced in the hydride transfer step.

PMID- 16959778
TI  - Differential cleavage of eIF4GI and eIF4GII in mammalian cells. Effects on
      translation.
AB  - Two isoforms of the translation initiation factor eIF4G, eIF4GI and eIF4GII, have
      been described in eukaryotic cells. The exact function of each isoform during the
      initiation of protein synthesis is still under investigation. We have developed
      an efficient and reliable method of expressing poliovirus 2Apro, which
      differentially proteolyzes eIF4GI and eIF4GII in a time- and dose-dependent
      manner. This system is based on the electroporation of an in vitro transcribed
      mRNA that contains the encephalomyocarditis virus internal ribosome entry site
      followed by the sequence of poliovirus 2Apro. In contrast to HeLa cells,
      expression of this protease in BHK-21 cells induces delayed hydrolysis kinetics
      of eIF4GI with respect to eIF4GII. Moreover, under these conditions the
      polyadenylate binding protein is not cleaved. Interestingly, translation of de
      novo synthesized luciferase mRNA is highly dependent on eIF4GI integrity, whereas
      ongoing translation is inhibited at the same time as eIF4GII cleavage. Moreover,
      reinitiation of a preexisting mRNA translation after polysome run-off is
      dependent on the integrity of eIF4GII. Notably, de novo translation of heat shock
      protein 70 mRNA depends little on eIF4GI integrity but is more susceptible to
      eIF4GII hydrolysis. Finally, translation of an mRNA containing
      encephalomyocarditis virus internal ribosome entry site when the two isoforms of
      eIF4G are differentially hydrolyzed has been examined.

PMID- 16959779
TI  - Mutual antagonism of target of rapamycin and calcineurin signaling.
AB  - Growth and stress are generally incompatible states. Stressed cells adapt to an
      insult by restraining growth, and conversely, growing cells keep stress responses
      at bay. This is evident in many physiological settings, including for example,
      the effect of stress on the immune or nervous system, but the underlying
      signaling mechanisms mediating such mutual antagonism are poorly understood. In
      eukaryotes, a central activator of cell growth is the protein kinase target of
      rapamycin (TOR) and its namesake signaling network. Calcineurin is a conserved,
      Ca(2+)/calmodulin-dependent protein phosphatase and target of the
      immunosuppressant FK506 (tacrolimus) that is activated in yeast during stress to
      promote cell survival. Here we show yeast mutants defective for TOR complex 2
      (TORC2) or the essential homologous TORC2 effectors, SLM1 and SLM2, exhibited
      constitutive activation of calcineurin-dependent transcription and actin
      depolarization. Conversely, cells defective in calcineurin exhibited SLM1
      hyperphosphorylation and enhanced interaction between TORC2 and SLM1.
      Furthermore, a mutant SLM1 protein (SLM1(DeltaC14)) lacking a sequence related to
      the consensus calcineurin docking site (PxIxIT) was insensitive to calcineurin,
      and SLM1(Delta)(C14) slm2 mutant cells were hypersensitive to oxidative stress.
      Thus, TORC2-SLM signaling negatively regulates calcineurin, and calcineurin
      negatively regulates TORC2-SLM. These findings provide a molecular basis for the
      mutual antagonism of growth and stress.

PMID- 16959780
TI  - C-terminal Src kinase-homologous kinase (CHK), a unique inhibitor inactivating
      multiple active conformations of Src family tyrosine kinases.
AB  - The Src family of protein kinases (SFKs) mediates mitogenic signal transduction,
      and constitutive SFK activation is associated with tumorigenesis. To prevent
      constitutive SFK activation, the catalytic activity of SFKs in normal mammalian
      cells is suppressed mainly by two inhibitors called C-terminal Src kinase (CSK)
      and CSK-homologous kinase (CHK), which inactivate SFKs by phosphorylating a
      consensus tyrosine near the C terminus of SFKs (Y(T)). The phosphorylated Y(T)
      intramolecularly binds to the SH2 domain of SFKs. This interaction, known as
      pY(T)/SH2 interaction, together with binding between the SH2 kinase linker and
      the SH3 domain of SFKs (linker/SH3 interaction) stabilizes SFKs in a "closed"
      inactive conformation. We previously discovered an alternative mechanism CHK
      employs to inhibit SFKs. This mechanism, referred to as the non-catalytic
      inhibitory mechanism, involves tight binding of CHK to SFKs; the binding alone is
      sufficient to inhibit SFKs. Herein, we constructed multiple active conformations
      of an SFK member, Hck, by systematically disrupting the two inhibitory
      interactions. We found that CHK employs the non-catalytic mechanism to inactivate
      these active conformations of Hck. However, CHK does not bind Hck when it adopts
      the inactive conformation in which both inhibitory interactions are intact. These
      data indicate that binding of CHK to SFKs via the non-catalytic mechanism is
      governed by the conformations of SFKs. Although CSK is also an inhibitor of SFKs,
      it does not inhibit SFKs by a similar non-catalytic mechanism. Thus, the non
      catalytic inhibitory mechanism is a unique property of CHK that allows it to down
      regulate multiple active conformations of SFKs.

PMID- 16959781
TI  - Glucocorticoids repress bcl-X expression in lymphoid cells by recruiting STAT5B
      to the P4 promoter.
AB  - The bcl-X gene plays a critical role in apoptosis. Six different isoforms
      generated by tissue-specific promoter usage and alternative splicing were
      described. Some of them exert opposite effects on cell death. In mammary
      epithelial cells glucocorticoids induce bcl-X expression and increase the ratio
      bcl-X(L) (antiapoptotic)/bcl-X(S) (apoptotic) by activating P4 promoter, which
      contains two hormone response elements. Here we show that, on mouse thymocytes
      and T lymphocyte derivative S49 cells, glucocorticoids inhibited transcription
      from P4 and decreased the ratio bcl-X(L)/bcl-X(S) favoring apoptosis. Upon
      hormonal treatment, glucocorticoid receptor (GR), steroid receptor coactivator-1,
      and RNA polymerase II were transiently recruited to P4 promoter, whereas STAT5B
      was also recruited but remained bound. Concomitant with the release of GR,
      silencing mediator for retinoic acid receptor and thyroid hormone receptor and
      histone deacetylase 3 were recruited, histone H3 was deacetylated, and RNA
      polymerase II left the promoter. Inhibition of STAT5 activity reverted
      glucocorticoid repression to activation of transcription and was accompanied by
      stable recruitment of GR and RNA polymerase II to P4.

PMID- 16959782
TI  - Transcription enhancer factor-1-dependent expression of the alpha-tropomyosin
      gene in the three muscle cell types.
AB  - In vertebrates, the actin-binding proteins tropomyosins are encoded by four
      distinct genes that are expressed in a complex pattern during development and
      muscle differentiation. In this study, we have characterized the transcriptional
      machinery of the alpha-tropomyosin (alpha-Tm) gene in muscle cells. Promoter
      analysis revealed that a 284-bp proximal promoter region of the Xenopus laevis
      alpha-Tm gene is sufficient for maximal activity in the three muscle cell types.
      The transcriptional activity of this promoter in the three muscle cell types
      depends on both distinct and common cis-regulatory sequences. We have identified
      a 30-bp conserved sequence unique to all vertebrate alpha-Tm genes that contains
      an MCAT site that is critical for expression of the gene in all muscle cell
      types. This site can bind transcription enhancer factor-1 (TEF-1) present in
      muscle cells both in vitro and in vivo. In serum-deprived differentiated smooth
      muscle cells, TEF-1 was redistributed to the nucleus, and this correlated with
      increased activity of the alpha-Tm promoter. Overexpression of TEF-1 mRNA in
      Xenopus embryonic cells led to activation of both the endogenous alpha-Tm gene
      and the exogenous 284-bp promoter. Finally, we show that, in transgenic embryos
      and juveniles, an intact MCAT sequence is required for correct temporal and
      spatial expression of the 284-bp gene promoter. This study represents the first
      analysis of the transcriptional regulation of the alpha-Tm gene in vivo and
      highlights a common TEF-1-dependent regulatory mechanism necessary for expression
      of the gene in the three muscle lineages.

PMID- 16959783
TI  - Characterization and classification of ATP-binding cassette transporter ABCA3
      mutants in fatal surfactant deficiency.
AB  - The ATP-binding cassette transporter ABCA3 is expressed predominantly at the
      limiting membrane of the lamellar bodies in lung alveolar type II cells. Recent
      study has shown that mutation of the ABCA3 gene causes fatal surfactant
      deficiency in newborns. In this study, we investigated in HEK293 cells the
      intracellular localization and N-glycosylation of the ABCA3 mutants so far
      identified in fatal surfactant deficiency patients. Green fluorescent protein
      tagged L101P, L982P, L1553P, Q1591P, and Ins1518fs/ter1519 mutant proteins
      remained localized in the endoplasmic reticulum, and processing of
      oligosaccharide was impaired, whereas wild-type and N568D, G1221S, and L1580P
      mutant ABCA3 proteins trafficked to the LAMP3-positive intracellular vesicle,
      accompanied by processing of oligosaccharide from high mannose type to complex
      type. Vanadate-induced nucleotide trapping and ATP-binding analyses showed that
      ATP hydrolysis activity was dramatically decreased in the N568D, G1221S, and
      L1580P mutants, accompanied by a moderate decrease in ATP binding in N568D and
      L1580P mutants but not in the G1221S mutant, compared with the wild-type ABCA3
      protein. In addition, mutational analyses of the Gly-1221 residue in the 11th
      transmembrane segment and the Leu-1580 residue in the cytoplasmic tail, and
      homology modeling of nucleotide binding domain 2 demonstrate the significance of
      these residues for ATP hydrolysis and suggest a mechanism for impaired ATP
      hydrolysis in G1221S and L1580P mutants. Thus, surfactant deficiency because of
      ABCA3 gene mutation may be classified into two categories as follows: abnormal
      intracellular localization (type I) and normal intracellular localization with
      decreased ATP binding and/or ATP hydrolysis of the ABCA3 protein (type II). These
      distinct pathophysiologies may reflect both the severity and effective therapy
      for surfactant deficiency.

PMID- 16959784
TI  - Hyaluronan constitutively regulates activation of multiple receptor tyrosine
      kinases in epithelial and carcinoma cells.
AB  - Hyaluronan (HA) is enriched in the pericellular matrices of many malignant human
      tumors, and manipulations of HA interactions have strong effects on tumor
      progression in animal models. Increased HA production stimulates ERBB2
      activation, leading to increased cell survival activities and several malignant
      cell properties. On the other hand, inhibition of constitutive HA-tumor cell
      interactions in malignant cells inhibits these properties. We have now
      investigated the role of HA in activation of several additional receptor tyrosine
      kinases (RTKs), i.e. IGF1R-beta, PDGFR-beta, EGFR and c-MET, in colon, prostate,
      and breast carcinoma cells. In each case we show that antagonists of endogenous
      HA interactions inhibit their tyrosine phosphorylation, i.e. activation. On the
      other hand, we show that these RTKs are activated in phenotypically normal or
      relatively benign tumor cells by experimentally increasing HA production. We also
      investigated the role of HA in constitutive versus ligand-induced activation of
      RTKs. In HCA7 colon and C4-2 prostate carcinoma cells, ERBB2 is constitutively
      activated in a ligand-independent manner, whereas IGF1R-beta and PDGFR-beta
      require ligand interaction for activation. We show that both constitutive
      activation of ERBB2 and ligand-mediated activation of IGF1R-beta and PDGFR-beta
      are reversed by co-treatment of the cells with a HA antagonist. We conclude that
      HA serves a general function in RTK activation.

PMID- 16959785
TI  - Oxidative stress causes heart failure with impaired mitochondrial respiration.
AB  - Elderly people insidiously manifest the symptoms of heart failure, such as
      dyspnea and/or physical disabilities in an age-dependent manner. Although
      previous studies suggested that oxidative stress plays a pathological role in the
      development of heart failure, no direct evidence has been documented so far. In
      order to investigate the pathological significance of oxidative stress in the
      heart, we generated heart/muscle-specific manganese superoxide dismutase
      deficient mice. The mutant mice developed progressive congestive heart failure
      with specific molecular defects in mitochondrial respiration. In this paper, we
      showed for the first time that the oxidative stress caused specific morphological
      changes of mitochondria, excess formation of superoxide (O(2)(*)(-)), reduction
      of ATP, and transcriptional alterations of genes associated with heart failure in
      respect to cardiac contractility. Accordingly, administration of a superoxide
      dismutase mimetic significantly ameliorated the symptoms. These results implied
      that O(2)(*)(-) generated in mitochondria played a pivotal role in the
      development and progression of heart failure. We here present a bona fide model
      for human cardiac failure with oxidative stress valuable for therapeutic
      interventions.

PMID- 16959786
TI  - Evidence for specificity in lipid-rhodopsin interactions.
AB  - The interaction of bovine rhodopsin with poly- and monounsaturated lipids was
      studied by (1)H MAS NMR with magnetization transfer from rhodopsin to lipid.
      Experiments were conducted on bovine rod outer segment (ROS) disks and on
      recombinant membranes containing lipids with polyunsaturated, docosahexaenoyl
      (DHA) chains. Poly- and monounsaturated lipids interact specifically with
      different sites on the rhodopsin surface. Rates of magnetization transfer from
      protein to DHA are lipid headgroup-dependent and increased in the sequence PC <
      PS < PE. Boundary lipids are in fast exchange with the lipid matrix on a time
      scale of milliseconds or shorter. All rhodopsin photointermediates transferred
      magnetization preferentially to DHA-containing lipids, but highest rates were
      observed for Meta-III rhodopsin. The experiments show clearly that the surface of
      rhodopsin has sites for specific interaction with lipids. Current theories of
      lipid-protein interaction do not account for such surface heterogeneity.

PMID- 16959787
TI  - Peroxisome proliferator-activated [corrected] receptor-gamma2 [corrected]
      Pro12Ala, interaction with alcohol intake and NSAID use, in relation to risk of
      breast cancer in a prospective study of Danes.
AB  - Use of non-steroid anti-inflammatory drugs (NSAIDs) has been associated with
      decreased risk of breast cancer in epidemiological studies. Thus, a high
      inflammatory response may be associated with increased breast cancer risk. It is
      thus possible that genetic variations leading to a modified inflammatory response
      will influence breast cancer risk. The purpose of this study was to determine if
      polymorphisms associated with an altered inflammatory response are associated
      with breast cancer risk, and to investigate the possible interaction with
      lifestyle factors such as alcohol use, smoking and NSAID use. We matched 361
      female breast cancer cases with 361 controls, nested within the prospective
      'Diet, Cancer and Health' study. Carriers of the variant Ala-allele of PPARgamma2
      Pro12Ala were at lower risk of breast cancer (IRR=0.67, 95% CI=0.46-0.97). This
      was primarily due to an interaction with alcohol consumption. Alcohol consumption
      was associated with a 1.21-fold increased risk of breast cancer per 10 g
      alcohol/day (95% CI=1.06-1.35) among homozygous wild-type carriers, whereas
      alcohol was not associated with breast cancer risk among variant allele carriers
      (P for interaction=0.005). Non-users of NSAID, who were carriers of the variant
      allele of PPARgamma2 Pro12Ala, were at lower risk of breast cancer (IRR=0.44; 95%
      CI=0.26-0.73) compared with non-users carrying wild-type alleles (P for
      interaction=0.03). No effects were found for IL6 G-174C, IL8 T-251A and COX2
      T8473C. Our results suggest that PPARgamma2 Pro12Ala is an important determinant
      in alcohol mediated breast carcinogenesis. We also observe interaction between
      NSAID, alcohol consumption and PPARgamma2 Pro12Ala genotype in relation to breast
      cancer risk.

PMID- 16959788
TI  - Uptake of biosimilar therapies--opportunities and obstacles. Commentary.

PMID- 16959789
TI  - Comparative testing and pharmacovigilance of biosimilars.
AB  - Unlike traditional generic pharmaceuticals, biosimilars (also called 'follow-on
      biopharmaceuticals' in the USA) aim to copy a complex recombinant, three
      dimensional protein structure with high molecular weight. Small changes in the
      manufacturing process can alter the product's effect and safety. According to the
      guidelines of the European Agency for the Evaluation of Medicinal products
      (EMEA), extensive comparability testing will be required to demonstrate that the
      biosimilar has a comparable profile in terms of quality, safety and efficacy as
      the reference product. Various analytical assays are available to compare
      physicochemical and biological properties between production batches of a
      potentially similar biopharmaceutical (comparability) and in comparison with a
      reference product (similarity). It is important to recognize the limits of
      existing assays so that the results can be accurately interpreted for market
      authorization. This article examines the quality and limits of such analytical
      methods. The analytical tests to demonstrate comparability and similarity of a
      biosimilar product to a reference drug with respect to protein content, activity,
      physiochemical integrity, stability, impurities and additives, as well as
      immunogenicity are discussed. Although several assays are available, reliable
      tests for safety and efficacy still require development. Furthermore,
      international standards are missing and materials and methods differ from
      laboratories making the comparison of results very difficult. Clinical trials and
      post-authorization pharmacovigilance are essential to guarantee the product's
      safety and efficacy over time. Pharmacovigilance, as part of a comprehensive risk
      management programme, will need to include regular testing for consistent
      manufacturing of the drug.

PMID- 16959790
TI  - European regulatory guidelines for biosimilars.
AB  - The impending arrival en masse of biosimilars on Western markets is placing drug
      regulatory agencies under pressure to realign their policies. Biosimilars require
      more rigorous assessments than traditional chemical generics. This is because of
      the molecular complexity of recombinant proteins, and the complexity of
      biological manufacturing processes. Small differences can arise in a recombinant
      protein product which are hard or impossible to detect with even state-of-the-art
      analytical techniques. Yet, these differences can have significant impact on the
      safety and efficacy of the drug. The European Medicines Agency (EMEA) has taken
      the lead in issuing guidelines, most of which are still under review. The
      guidelines advocate pre-clinical and clinical testing of biosimilars prior to
      market authorization, complemented by tailored pharmacovigilance plans. These
      guidelines provide a valuable base from which to develop in this evolving
      regulatory environment.

PMID- 16959791
TI  - The protein science of biosimilars.
AB  - A sea change is occurring in the off-patent drug manufacturing industry with a
      first wave of biotechnologically derived products reaching the end of their
      patent lives. However, recombinant proteins are in a different league from their
      chemical predecessors in terms of molecular complexity. Small differences in
      manufacturing processes can affect the efficacy and safety of the recombinant
      proteins in a manner which is not always measurable using analytical or in vitro
      techniques. Thus, comparable clinical profiles do not automatically follow from
      physicochemical likeness and can only be demonstrated through clinical studies.
      It is essential for patient safety that both innovator and biosimilar
      manufacturers ensure consistency in their production, by performing rigorous
      purity and activity profiling between batches, and implement tailored
      pharmacovigilance plans.

PMID- 16959792
TI  - Immunogenicity of biopharmaceuticals.
AB  - The availability of biopharmaceuticals has been increasing over the past decade
      and as their patents expire, the emergence of biosimilar agents approaches. The
      primary issue of concern for the safety of these agents is the potential for
      immunogenicity. Both product- and host-related factors have documented impact on
      the immune response, but many factors are still unknown. Although in many cases
      the presence of antibodies may have little clinical consequence, the upsurge of
      pure red cell aplasia cases further increased concerns about potential clinical
      consequences of extensive use of biopharmaceuticals and biosimilars. Available
      laboratory measurement methods are insufficient to predict biological and
      clinical properties of biopharmaceuticals, or even to compare their
      bioequivalence. Comparison of results from different studies is complicated by
      the variability of assay measurements, presentation of data and lack of
      standardization.

PMID- 16959793
TI  - Beta-synuclein modulates alpha-synuclein neurotoxicity by reducing alpha
      synuclein protein expression.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by
      fibrillar aggregates of alpha-synuclein in characteristic inclusions known as
      "Lewy bodies". As mutations altering alpha-synuclein structure or increasing
      alpha-synuclein expression level can cause familial forms of PD or related Lewy
      body disorders, alpha-synuclein is believed to play a central role in the process
      of neuron toxicity, degeneration and death in "synucleinopathies". beta-synuclein
      is closely related to alpha-synuclein and has been shown to inhibit alpha
      synuclein aggregation and ameliorate alpha-synuclein neurotoxicity. We generated
      beta-synuclein transgenic mice and observed a marked reduction in alpha-synuclein
      protein expression in the cortex of mice over-expressing beta-synuclein. This
      reduction in alpha-synuclein protein expression was not accompanied by decreases
      in alpha-synuclein mRNA expression. Using the prion protein promoter alpha
      synuclein A53T mouse model of PD, we demonstrated that over-expression of beta
      synuclein could retard the progression of impaired motor performance, reduce
      alpha-synuclein aggregation and extend survival in doubly transgenic mice. We
      attributed the amelioration of alpha-synuclein neurotoxicity in such bigenic mice
      to the ability of beta-synuclein to reduce alpha-synuclein protein expression
      based upon I(125) autoradiography quantification. Our findings indicate that
      increased expression of beta-synuclein protein results in a reduction of alpha
      synuclein protein expression. As increased expression of alpha-synuclein may
      cause or contribute to PD pathogenesis in sporadic and familial forms of disease,
      this observation has important implications for the development of therapies for
      PD.

PMID- 16959794
TI  - Impact of the DISC1 Ser704Cys polymorphism on risk for major depression, brain
      morphology and ERK signaling.
AB  - Disrupted-in-schizophrenia 1 (DISC1), identified in a pedigree with a familial
      psychosis with the chromosome translocation (1:11), is a putative susceptibility
      gene for psychoses such as schizophrenia and bipolar disorder. Although there are
      a number of patients with major depressive disorder (MDD) in the family members
      with the chromosome translocation, the possible association with MDD has not yet
      been studied. We therefore performed an association study of the DISC1 gene with
      MDD and schizophrenia. We found that Cys704 allele of the Ser704Cys single
      nucleotide polymorphism (SNP) was associated with an increased risk of developing
      MDD (P=0.005, odds ratio=1.46) and stronger evidence for association in a multi
      marker haplotype analysis containing this SNP (P=0.002). We also explored
      possible impact of Ser704Cys on brain morphology in healthy volunteers using MR
      imaging. We found a reduction in gray matter volume in cingulate cortex and a
      decreased fractional anisotropy in prefrontal white matter of individuals
      carrying the Cys704 allele compared with Ser/Ser704 subjects. In primary neuronal
      culture, knockdown of endogenous DISC1 protein by small interfering RNA resulted
      in the suppression of phosphorylation of ERK and Akt, whose signaling pathways
      are implicated in MDD. When effects of sDISC1 (Ser704) and cDISC1 (Cys704)
      proteins were examined separately, phosphorylation of ERK was greater in sDISC1
      compared with cDISC1. A possible biological mechanism of MDD might be implicated
      by these convergent data that Cys704 DISC1 is associated with the lower
      biological activity on ERK signaling, reduced brain gray matter volume and an
      increased risk for MDD.

PMID- 16959795
TI  - Alpha-synuclein acts in the nucleus to inhibit histone acetylation and promote
      neurotoxicity.
AB  - Alpha-synuclein is a neuronal protein implicated genetically in Parkinson's
      disease. alpha-synuclein localizes to the nucleus and presynaptic nerve
      terminals. Here we show that alpha-synuclein mediates neurotoxicity in the
      nucleus. Targeting of alpha-synuclein to the nucleus promotes toxicity, whereas
      cytoplasmic sequestration is protective in both cell culture and transgenic
      Drosophila. Toxicity of alpha-synuclein can be rescued by administration of
      histone deacetylase inhibitors in both cell culture and transgenic flies. Alpha
      synuclein binds directly to histones, reduces the level of acetylated histone H3
      in cultured cells and inhibits acetylation in histone acetyltransferase assays.
      Alpha-synuclein mutations that cause familial Parkinson's disease, A30P and A53T,
      exhibit increased nuclear targeting in cell culture. These findings implicate
      nuclear alpha-synuclein in promoting nigrostriatal degeneration in Parkinson's
      disease and encourage exploration of histone deacetylase inhibitors as potential
      therapies for the disorder.

PMID- 16959796
TI  - Identification of the positive regulatory and distinct core regions of promoters,
      and transcriptional regulation in three types of mouse phospholipid hydroperoxide
      glutathione peroxidase.
AB  - Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is transcribed into
      three types of mRNA, mitochondrial, non-mitochondrial and nucleolar types, from
      one gene by alternative transcription using different first exons, Ia and Ib. We
      investigated the regulatory mechanisms of the expressions of the three types of
      PHGPx using promoter analysis with luciferase as the reporter gene and
      electrophoretical mobility shift analysis. Here we report a draft of the positive
      regulatory region and the core promoter regions of PHGPx in several cell lines.
      From promoter deletion analysis we identified the three distinct core regions of
      mitochondrial PHGPx, non-mitochondrial PHGPx and nucleolar PHGPx. The core
      promoter activity of non-mitochondrial PHGPx was high in L929 cells, but
      relatively low for mitochondrial and nucleolar PHGPx. We also identified the
      positive regulatory region of mitochondrial PHGPx by deletion and mutation
      analysis of 5'-flanking regions of mitochondrial PHGPx. This region could
      regulate the promoter activity of non-mitochondrial PHGPx; however, up-regulation
      by this region was normally suppressed by the upstream region in somatic cells.
      Electrophoretical mobility shift analysis demonstrated that a specific
      transcription factor complex bound to this region in adult testis, but not in
      young testis and different sizes of complexes bound to this region between testis
      and brain.

PMID- 16959797
TI  - The antioxidant role of a reagent, 2',7'-dichlorodihydrofluorescin diacetate,
      detecting reactive-oxygen species and blocking the induction of heme oxygenase-1
      and preventing cytotoxicity.
AB  - Heme oxygenase-1 (HO-1) degrades heme into biliverdin, iron and CO. The enzyme
      participates in adaptive and protective responses to oxidative stress and various
      inflammatory stimuli, and is induced in response to reactive oxygen species
      (ROS). 2',7'-Dichlorodihydrofluorescin diacetate (DCFH-DA) is a common reagent
      used to detect ROS by the oxidation of 2',7'-dichlorodihydrofluorescin (DCFH) to
      fluorescent dichlorodihydrofluorescein. We previously found that rapid oxidation
      of DCFH occurred with heme-compounds as well as ROS [Ohashi, T. et al. (2002)
      FEBS Lett. 511, 21-27], and then examined the effect of DCFH-DA on the induction
      of HO-1 expression by arsenite, cadmium and hemin, which induce oxidative stress
      and cytotoxicity. We found suppression of the arsenite-, cadmium- and hemin
      dependent induction of HO-1 with DCFH-DA. The suppression occurred at the
      transcriptional level since the promoter activity of the Maf-recognition site of
      the HO-1 gene decreased with the DCFH-DA treatment. DCFH abolished the
      phosphorylation of extracellular signal-regulated kinase, the nuclear
      translocation of a transcriptional activator Nrf2, and cell death. An
      antioxidant, N-acetylcysteine (NAC), also suppressed the induction by arsenite
      and cadmium, but not that by hemin, indicating that DCFH blocked a different site
      in the stress signal pathway from NAC. Considering that the oxidation of DCFH
      diminishes ROS generated by various stressors, our findings provide a potential
      strategy for protection of cells from toxic insults using DCFH-like molecules.

PMID- 16959798
TI  - Nurse Aides' ratings of the resident safety culture in nursing homes.
AB  - PURPOSE: First, the resident safety culture of nursing homes from a Nurse Aide's
      perspective was compared with existing data from hospitals. Second, how the
      safety culture of nursing homes varied according to facility characteristics and
      market characteristics was examined. METHODS: Data came from 72 nursing homes and
      1579 Nurse Aides (response rate of 55%). From these nursing homes, Nurse Aides
      completed The Hospital Survey on Patient Safety Culture (HSOPSC) instrument, a
      previously validated survey with 12 subscales used to assess safety culture. The
      nursing home scores from this instrument were compared with the hospital scores.
      Ordinary least squares regression was used to examine the association between
      nine nursing home facility characteristics and two market characteristics and the
      overall safety culture score. RESULTS: All of the 12 HSOPSC subscale scores from
      the nursing home sample were considerably lower than the benchmark hospital
      scores, indicating a less well-developed safety culture. The significant facility
      and market characteristics from the regression analysis resembled many of those
      found when similar characteristics are used in examinations of quality.
      CONCLUSIONS: These results are important in clearly showing that the resident
      safety culture of Nurse Aides in many nursing homes may be poorly developed.

PMID- 16959799
TI  - Effects of visitation among allied health professionals.
AB  - OBJECTIVE: Visitation is a method for external peer review. The goal is to
      improve the quality of patient care by giving feedback on quality of competence
      and performance of a professional during a practice visit. Feedback is offered as
      recommendations for improvement. This study aims to evaluate the effects of
      visitation and to determine which factors are related to the effectiveness of
      visitation. PARTICIPANTS: Members of seven allied health professions in the
      Netherlands: dieticians, exercise therapists, physiotherapists, dental
      hygienists, occupational therapists, podiatrists, and radiology assistants.
      DESIGN: Evaluation questionnaires were sent to 151 allied health professionals
      who had participated in visitation. The questions included all practice
      management aspects that had been assessed during the practice visit. The effects
      of visitation were studied at three levels: change in awareness of weak and
      strong aspects of competence and performance, intention to carry out
      recommendations, and actual improvements. RESULTS: Results showed effects of
      visitation on all three levels. Respondents intended to carry out two-thirds of
      the recommendations. Visitation led to a better awareness of weak points on 36%
      of the aspects and better awareness of strong points on 53% of the aspects of
      practice management. Young respondents reported more changes in awareness than
      older respondents. Actual improvements were carried out on 33% of the aspects.
      CONCLUSIONS: Visitation is an effective method to stimulate quality improvement
      in allied health professionals. Although changes in awareness more often occurred
      in younger respondents, actual improvements were made by all respondents.

PMID- 16959800
TI  - Considered judgement in evidence-based guideline development.
AB  - BACKGROUND: Clinical practice guidelines should be based on the best available
      evidence. However, this evidence is often incomplete, controversial, or lacking.
      Other considerations beyond the evidence are therefore needed to be able to
      formulate specific and applicable recommendations for clinical practice.
      OBJECTIVE: The aim of this study is to obtain consensus among experts about a set
      of domains and items covering the most relevant 'other considerations' to
      formulate recommendations in evidence-based guideline development. METHODS: An
      initial list of 10 domains and 49 items for a systematic and considered judgement
      of scientific evidence was generated from the literature. A panel of Dutch
      experts in guideline development tested this list using a two-round Delphi
      consensus technique. Each expert was asked to independently score the relevance
      of the items on a 4-point Likert scale, ranging from 'very important' to 'not
      important'. The final list consisted of items that were included by at least 60%
      consensus. RESULTS: Twenty-eight experts participated in the first Delphi round
      and 21 of them in the second round. High scoring domains were 'clinical
      relevance', 'safety', and 'availability of resources'. There was consensus about
      the relevance of 37 items. The domain 'conflicts of interest by industry' was
      excluded because of lack of consensus. CONCLUSION: This is the first formal
      consensus approach towards structuring the considered judgement process in
      formulating recommendations in clinical guidelines. The final list of items can
      be used to facilitate the process of guideline development. The next step is to
      test the practical usefulness and applicability of this list in guideline
      development.

PMID- 16959801
TI  - In terms of safety.

PMID- 16959802
TI  - Adiponectin and myocardial infarction: A paradox or a paradigm?

PMID- 16959803
TI  - Registries and surveys in acute coronary syndrome.

PMID- 16959804
TI  - Posthumous sperm retrieval: analysis of time interval to harvest sperm.
AB  - BACKGROUND: Current recommendations regarding posthumous sperm retrieval (PSR)
      are based on a small number of cases. Our purpose was to determine the time
      interval from death to a successful procedure. METHODS: Seventeen consecutive PSR
      procedures in 14 deceased and 3 neurologically brain-dead patients at two male
      infertility centres [Sheba Medical Center (SMC), Tel-Hashomer, Israel and
      University of California San Francisco (UCSF), San Francisco, CA, USA] were
      analysed. Main outcome measures were retrieval of vital sperm, pregnancies and
      births. RESULTS: PSR methods included resection of testis and epididymis (n = 8),
      en-block excision of testis, epididymis and proximal vas deferens with vasal
      irrigation (n = 6), electroejaculation (EEJ) (n = 2) and epididymectomy (n = 1).
      PSR was performed 7.5-36 h after death. Sperm was retrieved in all cases and was
      motile in 14 cases. In two cases, testicular and epididymal tissues were
      cryopreserved without sperm evaluation, and in one case, no motility was
      detected. IVF and ICSI were performed in two cases in which sperm had been
      retrieved 30 h after death, and both resulted in pregnancies and live births.
      CONCLUSIONS: Viable sperm is obtainable with PSR well after the currently
      recommended 24-h time interval. PSR should be considered up to 36 h after death,
      following appropriate evaluation. No correlation was found between cause of death
      and chance for successful sperm retrieval.

PMID- 16959805
TI  - Uptake and distribution of catechins in fetal organs following in utero exposure
      in rats.
AB  - BACKGROUND: Although catechins are known to be powerful antioxidants, no reports
      have shown their transport to fetal organs. We investigated the distribution of
      catechins in fetal rat organs after maternal exposure to green tea extract (GTE).
      METHODS: GTE (550 mg/kg) or water was fed orally to pregnant dams at 15.5 days of
      gestation, the dams were sacrificed and fetal organs were dissected 0, 0.5, 1, 2,
      3, 5, and 8 h later. Catechins and catechin gallates were determined by high
      performance liquid chromatography (HPLC) after solid-phase extraction. RESULTS:
      In the GTE-treated group, catechins were detected in most of the fetal organs
      studied, including the brain, eyes, heart, lungs, kidneys and liver but not in
      the control group. The first peak times (T(max)) were about 0.5-1 h. The maximum
      concentrations (C(max)) of catechins in the fetal eye were about 2-10 times
      higher than in the other organs, ranging from 249 pmol/g for epicatechin (EC) to
      831 pmol/g for epigallocatechin gallate (EGCG). Catechin gallates were generally
      more readily taken up by fetal organs than catechins. EGCG had the highest level
      of uptake according to area under the curve (AUC) plots and the highest C(max) in
      all organs. CONCLUSIONS: Various fetal organs had low but significant levels of
      catechins after GTE intake by the dams, and organ levels were found to be related
      to catechin structure. EGCG could be a potential candidate for antioxidant
      supplementation of the fetus in utero.

PMID- 16959806
TI  - Human Reproduction--the next phase in its development.

PMID- 16959807
TI  - Correlation between first trimester fetal bone length and maternal serum
      pregnancy-associated plasma protein-A (PAPP-A).
AB  - BACKGROUND: Pregnancy-associated plasma protein-A (PAPP-A) is produced by the
      embryo and placenta during pregnancy, and its maternal serum concentrations are
      related to subsequent fetal growth. Evidence from animal models and in vitro
      experiments suggests that PAPP-A is particularly involved in the regulation of
      bone development. The aim of this study was to assess the correlation between
      late first trimester fetal bone length and maternal serum levels of PAPP-A.
      METHODS: In a cross-sectional observational study, ultrasound measurements of
      fetal long bones and fluorimetric immunoassays for maternal serum PAPP-A were
      performed in 514 singleton pregnancies at 10-14 weeks of gestation. RESULTS:
      There were 501 uncomplicated pregnancies. There were significant correlations
      between PAPP-A values and length of humerus, femur and tibia [r values 0.12 (P =
      0.01), 0.11 (P = 0.01) and 0.10 (P = 0.03), respectively]. The association with
      the length of ulna and foot did not reach statistical significance (r values 0.08
      and -0.03, respectively). CONCLUSIONS: Maternal serum PAPP-A levels at 10-14
      weeks of gestation are significantly associated with the length of fetal long
      bones such as humerus, femur and tibia. This provides further evidence that PAPP
      A may be involved in the regulation of bone development.

PMID- 16959808
TI  - Immunogenicity study of recombinant human sperm-associated antigen 9 in bonnet
      macaque (Macaca radiata).
AB  - BACKGROUND: The human sperm-associated antigen 9 (hSPAG9) is of special interest
      attributing to the findings indicating that SPAG9 is an acrosomal molecule. SPAG9
      is not only restricted to acrosomal compartment but also persists in equatorial
      segment post-acrosome reaction, which is a key location in sperm-egg interaction.
      METHODS AND RESULTS: Immunogenicity studies in macaques were carried out with
      recombinant hSPAG9 (rhSPAG9) adsorbed on alum, which resulted in high titres of
      anti-rhSPAG9 antibodies as determined by enzyme-linked immunosorbent assay
      (ELISA). Immunoblotting analysis employing anti-rhSPAG9 antibodies generated in
      monkeys indicated that antibodies specifically reacted with native SPAG9 from
      macaque and human sperm and rhSPAG9 protein. Furthermore, indirect
      immunofluorescence experiments demonstrated SPAG9 localization in the acrosomal
      compartment of macaque and human sperm. In addition, monkey antibodies against
      rhSPAG9 significantly inhibited the human spermatozoa adherence or penetration in
      zona-free hamster oocytes. CONCLUSION: These results demonstrate that rhSPAG9
      adsorbed on alum is highly immunogenic in subhuman primate model and therefore
      represents a suitable sperm-based vaccine immunogen for fertility trials in
      macaque.

PMID- 16959809
TI  - A qualitative study of the experience of treatment for infertility among women
      who successfully became pregnant.
AB  - BACKGROUND: In a study in which 18,503 women who had recently given birth were
      interviewed, 460 women who had received treatment for infertility (2.6%) were
      asked to participate in a postal study. The aim was to investigate the experience
      of women who had undergone treatment for infertility and given birth as a
      consequence, focusing on perceptions of treatment and care. METHODS: The study
      relies on responses to open-ended questions about the impact of treatment, how
      treatment could be improved and advice to policy makers. The text responses to
      these questions were analysed qualitatively. RESULTS: A total of 230 women
      responded (50%). Emergent themes related to the treatment process, pain and
      distress, lack of choice and control, timing, emotional and financial costs,
      fairness and contrasts in care. CONCLUSIONS: Women wished to be treated with
      respect and dignity and given appropriate information and support. They wanted
      their distress recognized, to feel cared for and to have confidence in health
      professionals in situations where outcomes are uncertain. Women acknowledged
      receiving care from motivated and skilled health professionals and value the
      children they have enormously. For many, there is now a sense of being complete,
      though for some this has been at great emotional and financial cost.

PMID- 16959810
TI  - WNT4 deficiency--a clinical phenotype distinct from the classic Mayer-Rokitansky
      Kuster-Hauser syndrome: a case report.
AB  - The pathways leading to female sexual determination in mammals are incompletely
      defined. Loss-of-function mutations in the WNT4 gene appear to cause
      developmental abnormalities of sexual differentiation in women and mice. We
      recruited six patients with different degrees of Mullerian abnormalities, with or
      without renal aberrations and a normal female 46,XX karyotype. A clear androgen
      excess was found only in one patient. This 19-year-old woman was affected by
      primary amenorrhoea, absence of Mullerian ducts derivatives, clinical (acne and
      hirsutism) and biochemical (repeatedly high levels of testosterone) signs of
      androgen excess. Direct sequencing of her WNT4 gene followed by functional
      studies in human ovarian cells (OVCAR3) was performed. This patient carried the
      novel R83C loss-of-function dominant negative mutation in her WNT4, confirming
      the role of WNT4 in the development and maintenance of the female phenotype in
      women. Our study can also help refine the phenotype of WNT4 deficiency in humans.
      In fact, it appears that at least in this limited casuistic small group of
      patients, the absence of a uterus (and not other Mullerian abnormalities) and the
      androgen excess are the pathognomonic signs of WNT4 defects, suggesting that this
      might be a clinical entity distinct from the classic Mayer-Rokitansky-Kuster
      Hauser syndrome.

PMID- 16959811
TI  - Endometriosis involving the ileocaecal junction with regional lymph node
      involvement in the baboon--striking pathological finding identical between the
      human and the baboon: a case report.
AB  - The baboon is an established model for endometriosis research. This report
      describes the occurrence of spontaneous endometriosis involving the ileocaecal
      junction and associated regional lymph nodes in the baboon. All endometriotic
      foci lacked the nuclear atypia, abnormal mitotic activity and altered nuclear-to
      cytoplasmic ratio typical of malignancy. These findings are identical to reports
      in the human in which ileocaecal and colonic endometriosis is associated with
      endometriosis in pericolonic and mesenteric lymph nodes. The similarity between
      baboon and human colonic endometriosis in both location and pathology is striking
      and lends further evidence supporting the validity of the baboon as a model for
      human endometriosis.

PMID- 16959812
TI  - One year of musical training affects development of auditory cortical-evoked
      fields in young children.
AB  - Auditory evoked responses to a violin tone and a noise-burst stimulus were
      recorded from 4- to 6-year-old children in four repeated measurements over a 1
      year period using magnetoencephalography (MEG). Half of the subjects participated
      in musical lessons throughout the year; the other half had no music lessons.
      Auditory evoked magnetic fields showed prominent bilateral P100m, N250m, P320m
      and N450m peaks. Significant change in the peak latencies of all components
      except P100m was observed over time. Larger P100m and N450m amplitude as well as
      more rapid change of N250m amplitude and latency was associated with the violin
      rather than the noise stimuli. Larger P100m and P320m peak amplitudes in the left
      hemisphere than in the right are consistent with left-lateralized cortical
      development in this age group. A clear musical training effect was expressed in a
      larger and earlier N250m peak in the left hemisphere in response to the violin
      sound in musically trained children compared with untrained children. This
      difference coincided with pronounced morphological change in a time window
      between 100 and 400 ms, which was observed in musically trained children in
      response to violin stimuli only, whereas in untrained children a similar change
      was present regardless of stimulus type. This transition could be related to
      establishing a neural network associated with sound categorization and/or
      involuntary attention, which can be altered by music learning experience.

PMID- 16959813
TI  - Diffusion tensor imaging with quantitative fibre tracking in HIV infection and
      alcoholism comorbidity: synergistic white matter damage.
AB  - A substantial proportion of individuals infected with human immunodeficiency
      virus (HIV) also abuse alcohol. Given that each condition can disrupt brain
      structural integrity, with a predilection for white matter, we used MR diffusion
      tensor imaging (DTI) and quantitative fibre tracking to examine the separate and
      combined effects on the microstructure of the corpus callosum. Subjects were men
      and women with alcoholism alone (n = 87), HIV infection alone (n = 42),
      alcoholism and HIV infection comorbidity (n = 52) and non-affected controls (n =
      88). The two alcoholism groups had similar lifetime alcohol consumption
      histories; the two HIV-infected groups had similar CD4+ counts and viral loads;
      all groups were matched in body mass index, and no participant was demented.
      Compared with controls, all patient groups had lower fractional anisotropy (FA)
      and higher mean diffusivity (MD) in callosal regions and fibre bundles coursing
      through the genu and splenium, but these effects were only significant in the two
      groups with alcoholism, which exhibited 0.65-1.2 SD abnormalities in FA and MD.
      The callosal regions were differentially affected by alcoholism, with the genu
      more affected than the splenium, a pattern even more pronounced in the fibre
      tracks. When the HIV-infected groups were divided by disease severity defined as
      an acquired immunodeficiency syndrome (AIDS)-defining event or low CD4+ counts
      (<200) and alcoholism comorbidity, the HIV-infected subgroup with AIDS and
      alcoholism exhibited approximately 2 SD FA and MD abnormalities in the callosal
      sectors and fibres, abnormalities that were more than twice the effect sizes
      observed in the other three HIV-infected subgroups. Degradation of the callosal
      microstructure was consistently associated with alcoholism, with evidence for
      compounded alcoholism-HIV effects. Functional relevance of the microstructural
      abnormalities was supported by associations between motor deficits and low FA or
      high MD within the diagnostic groups. The high prevalence of alcoholism in HIV
      infected individuals and the interfering effect of alcohol on HIV pharmacological
      response and therapy compliance underscore the need to recognize the independent
      and synergistic contributions of each condition to brain structure and function.

PMID- 16959814
TI  - Musical alexia with recovery: a personal account.
AB  - I describe the experience of an acute loss of ability to read music and play the
      piano accurately and expressively following an embolic infarct of the right
      angular and supramarginal gyri in a setting of chronic migraine. Other parietal
      deficits included a small visual field defect, visual hallucinations,
      prosopagnosia, topographical disorientation, disturbance of perception of
      velocity of moving objects and dyscalculia. Recovery began within a month of the
      ictus after instituting a regular practice routine. The ability to read and play
      polyphony recovered before the ability to read homophonic music. A substantial
      degree of recovery of musical function occurred within 6 months and of the other
      parietal deficits over a year. Failure to maintain regular practice led to marked
      though recoverable deterioration. An increased frequency of migraine persisted
      for some 18 months.

PMID- 16959815
TI  - Phenotype associated with APP duplication in five families.
AB  - Different duplications of the APP locus have been identified in five families
      with autosomal dominant early onset Alzheimer's disease (ADEOAD) and Abeta
      related cerebral amyloid angiopathy (CAA). This study describes the phenotype of
      this new entity. Clinical, neuropsychological, imagery and neuropathological data
      were reviewed. The phenotype was not dependent on the size of the duplication and
      there was no clinical feature of Down's syndrome. Dementia was observed in all
      cases; intracerebral haemorrhage (ICH) was reported in 6 (26%) and seizures
      occurred in 12 (57%) of 21 patients. Age of onset of dementia ranged from 42 to
      59 years, ICH from 53 to 64 years and age at death from 46 to 75 years. The
      neuropathological findings in five cases demonstrated Alzheimer's disease and
      severe CAA lesions that were reminiscent from those reported in brains of Down's
      syndrome patients. A striking feature consisted in intraneuronal Abetax-40
      accumulation located in the granular cell layer of the dentate gyrus and in the
      pyramidal cell layer of the Ammon's horn.

PMID- 16959816
TI  - Making non-fluent aphasics speak: sing along!
AB  - A classic observation in neurology is that aphasics can sing words they cannot
      pronounce otherwise. To further assess this claim, we investigated the production
      of sung and spoken utterances in eight brain-damaged patients suffering from a
      variety of speech disorders as a consequence of a left-hemisphere lesion. In
      Experiment 1, the patients were tested in the repetition and recall of words and
      notes of familiar material. Lyrics of familiar songs, as well as words of
      proverbs and prayers, were not better pronounced in singing than in speaking.
      Notes were better produced than words. In Experiment 2, the aphasic patients
      repeated and recalled lyrics from novel songs. Again, they did not produce more
      words in singing than in speaking. In Experiment 3, when allowed to sing or speak
      along with an auditory model while learning novel songs, aphasics repeated and
      recalled more words when singing than when speaking. Reduced speed or shadowing
      cannot account for this advantage of singing along over speaking in unison. The
      results suggest that singing in synchrony with an auditory model--choral singing-
      is more effective than choral speech, at least in French, in improving word
      intelligibility because choral singing may entrain more than one auditory-vocal
      interface. Thus, choral singing appears to be an effective means of speech
      therapy.

PMID- 16959817
TI  - Emotional responses to unpleasant music correlates with damage to the
      parahippocampal cortex.
AB  - Music is typically a pleasurable experience. But under certain circumstances,
      music can also be unpleasant, for example, when a young child randomly hits piano
      keys. Such unpleasant musical experiences have been shown to activate a network
      of brain structures involved in emotion, mostly located in the medial temporal
      lobe: the parahippocampal gyrus, amygdala, hippocampus and temporal pole.
      However, the differential roles of these regions remain largely unknown. In this
      study, pleasant and unpleasant music was presented to 17 patients with variable
      excisions of the medial temporal lobe, as well as to 19 matched controls. The
      pleasant music corresponded to happy and sad selections taken from the classical
      instrumental repertoire; the unpleasant music was the dissonant arrangement of
      the same selections. Only patients with substantial resections of the left or
      right parahippocampal cortex (PHC) gave highly abnormal judgements to dissonant
      music; they rated dissonant music as slightly pleasant while controls found it
      unpleasant. This indifference to dissonance was correlated with the remaining
      volume in the PHC, but was unrelated to the volume of the surrounding structures.
      The impairment was specific: the same patients judged consonant music to be
      pleasant, and were able to judge music as happy or sad. Furthermore, this lack of
      responsiveness to unpleasantness was not due to a perceptual disorder, because
      all patients were able to detect intentional errors in the musical excerpts.
      Moreover, the impairment differed from that induced by amygdala damage alone.
      These findings are consistent with a two-dimensional model of defensive responses
      to aversive stimuli, in which the PHC and the amygdala subserve different roles.

PMID- 16959818
TI  - The extent of resection of FDG-PET hypometabolism relates to outcome of temporal
      lobectomy.
AB  - A significant minority of patients undergoing surgery for medically refractory
      non-lesional temporal lobe epilepsy (TLE) continue to have seizures, but the
      reasons for this are uncertain. Fluorodeoxyglucose (FDG) PET shows hypometabolism
      in a majority of patients with non-lesional TLE, even in the absence of
      hippocampal atrophy. We examined whether the extent of resection of the area of
      FDG-PET hypometabolism influenced outcome following surgery for non-lesional TLE.
      Twenty-six patients who underwent temporal lobectomy for medically refractory TLE
      with at least 12 months follow-up were studied. The preoperative FDG-PET was
      compared with 20 non-epileptic controls using SPM99 to identify regions of
      significant hypometabolism (P < 0.0005, cluster > 200). This image was then co
      registered to the postoperative MRI scan. The volume of the FDG-PET
      hypometabolism that lay within the area of the resected temporal lobe was
      calculated. The volume of temporal lobe resected was also calculated. Patients
      with a good outcome had a greater proportion of the total FDG-PET hypometabolism
      volume resected than those with a poor outcome (24.1% versus 11.8%, P = 0.02).
      There was no significant difference between the groups in the volume of temporal
      lobe resected (P = 0.86). Multivariate regression demonstrated that the extent of
      resection of the hypometabolism significantly correlated with outcome (P = 0.03),
      independent of the presence of hippocampal sclerosis (P = 0.03) and total brain
      volume of hypometabolism (P = 0.45). The extent of resection of the region of
      hypometabolism on the preoperative FDG-PET is predictive of outcome following
      surgery for non-lesional TLE. Strategies that tailor resection extent to regional
      hypometabolism may warrant further evaluation.

PMID- 16959820
TI  - Sympathoexcitatory response to peripheral chemoreflex activation is enhanced in
      juvenile rats exposed to chronic intermittent hypoxia.
AB  - In the present study, we tested the hypothesis that chronic intermittent hypoxia
      (CIH) produces changes in the autonomic and respiratory responses to acute
      peripheral chemoreflex activation. To attain this goal, 3-week-old rats were
      exposed to 10 days of CIH (6% O(2) for 40 s at 9 min intervals; 8 h day(-1)).
      They were then used to obtain a working heart-brainstem preparation and, using
      this unanaesthetized experimental preparation, the chemoreflex was activated with
      potassium cyanide (0.05%, injected via the perfusion system), and the thoracic
      sympathetic nerve activity (tSNA), heart rate and phrenic nerve discharge (PND)
      were recorded. Rats subjected to CIH (n = 12), when compared with control animals
      (n = 12), presented the following significant changes in response to chemoreflex
      activation: (a) an increase in tSNA (78 +/- 4 versus 48 +/- 3%); (b) a long
      lasting increase in the frequency of the PND at 20 (0.52 +/- 0.03 versus 0.36 +/-
      0.03 Hz) and 30 s (0.40 +/- 0.02 versus 0.31 +/- 0.02 Hz) after the stimulus; and
      (c) a greater bradycardic response (-218 +/- 20 versus -163 +/- 16 beats min(
      1)). These results indicate that the autonomic and respiratory responses to
      chemoreflex activation in juvenile rats previously submitted to CIH are greatly
      increased.

PMID- 16959821
TI  - Enteric-formulated lactoferrin was more effectively transported into blood
      circulation from gastrointestinal tract in adult rats.
AB  - We have previously demonstrated that intestinally infused bovine lactoferrin
      (bLF) is transported into the blood circulation via the lymphatic pathway, not
      via the portal circulation. Therefore, in the present study, we further
      investigated whether intragastrically infused enteric-formulated bLF (EF-bLF) was
      more efficiently absorbed than bLF from the intestine in adult rats. The rats
      were randomly divided into three groups: 30 and 300 mg kg(-1) non-enteric
      formulated bLF (non-EF-bLF) groups and a 30 mg kg(-1) EF-bLF group. Thoracic
      lymph was collected from a thoracic lymph duct under general anaesthesia. Bovine
      lactoferrin was infused into the stomach or duodenal lumen via a needle for a
      period of over 1 min in a volume of 1 ml kg(-1). The bLF transported into the
      lymph was assayed quantitatively by double-antibody enzyme-linked immunosorbent
      assay (ELISA). Following the intragastric administration of bLF, the three groups
      showed almost the same lymph flow, but the bLF concentration in the lymph fluid
      in the EF-bLF group increased significantly and peaked 3 h after administration.
      With intraduodenal administration, the bLF concentration in the lymph fluid of
      the higher non-EF-bLF group was significantly higher than those of the other
      groups. The amount of absorbed bLF in the EF-bLF group was, however, about 10
      times higher than that in the lower non-EF-bLF group, when it was administered
      intragastrically. These data show that enteric-formulated bLF is less susceptible
      to gastric pepsin and is more efficiently absorbed from the intestine than is non
      enteric-formulated bLF.

PMID- 16959822
TI  - Renal hypoplasia and dysplasia: starting to put the puzzle together.

PMID- 16959823
TI  - The downside of a drug-crazed world.

PMID- 16959824
TI  - mRNA translation: unexplored territory in renal science.
AB  - Ambient protein levels are under coordinated control of transcription, mRNA
      translation, and degradation. Whereas transcription and degradation mechanisms
      have been studied in depth in renal science, the role of mRNA translation, the
      process by which peptide synthesis occurs according to the genetic code that is
      present in the mRNA, has not received much attention. mRNA translation occurs in
      three phases: Initiation, elongation, and termination. Each phase is controlled
      by unique eukaryotic factors. In the initiation phase, mRNA and ribosomal
      subunits are brought together. During the elongation phase, amino acids are added
      to the nascent peptide chain in accordance with codon sequences in the mRNA.
      During the termination phase, the fully synthesized peptide is released from the
      ribosome for posttranslational processing. Signaling pathways figure prominently
      in regulation of mRNA translation, particularly the phosphatidylinositol 3 kinase
      Akt-mammalian target of rapamycin pathway, the AMP-activated protein kinase
      tuberous sclerosis complex protein 1/tuberous sclerosis complex protein 2-Rheb
      pathway, and the extracellular signal-regulated kinase 1/2 type mitogen-activated
      protein kinase signaling pathway; there is significant cross-talk among these
      pathways. Regulation by mRNA translation is suggested when changes in mRNA and
      protein levels do not correlate and in the setting of rapid protein synthesis.
      Ongoing work suggests an important role for mRNA translation in compensatory
      renal growth, hypertrophy and extracellular matrix synthesis in diabetic
      nephropathy, growth factor synthesis by kidney cells, and glomerulonephritis.
      Considering that mRNA translation plays an important role in cell growth,
      development, malignancy, apoptosis, and response to stress, its study should
      provide novel insights in renal physiology and pathology.

PMID- 16959825
TI  - Vasopressin increases plasma membrane accumulation of urea transporter UT-A1 in
      rat inner medullary collecting ducts.
AB  - Urea transport, mediated by the urea transporter A1 (UT-A1) and/or UT-A3, is
      important for the production of concentrated urine. Vasopressin rapidly increases
      urea transport in rat terminal inner medullary collecting ducts (IMCD). A
      previous study showed that one mechanism for rapid regulation of urea transport
      is a vasopressin-induced increase in UT-A1 phosphorylation. This study tests
      whether vasopressin or directly activating adenylyl cyclase with forskolin also
      increases UT-A1 accumulation in the plasma membrane of rat IMCD. Inner medullas
      were harvested from rats 45 min after injection with vasopressin or vehicle. UT
      A1 abundance in the plasma membrane was significantly increased in the membrane
      fraction after differential centrifugation and in the biotinylated protein
      population. Vasopressin and forskolin each increased the amount of biotinylated
      UT-A1 in rat IMCD suspensions that were treated ex vivo. The observed changes in
      the plasma membrane are specific, as the amount of biotinylated UT-A1 but not the
      calcium-sensing receptor was increased by forskolin. Next, whether forskolin or
      the V(2)-selective agonist dDAVP would increase apical membrane expression of UT
      A1 in MDCK cells that were stably transfected with UT-A1 (UT-A1-MDCK cells) was
      tested. Forskolin and dDAVP significantly increased UT-A1 abundance in the apical
      membrane in UT-A1-MDCK cells. It is concluded that vasopressin and forskolin
      increase UT-A1 accumulation in the plasma membrane in rat IMCD and in the apical
      plasma membrane of UT-A1-MDCK cells. These findings suggest that vasopressin
      regulates urea transport by increasing UT-A1 accumulation in the plasma membrane
      and/or UT-A1 phosphorylation.

PMID- 16959826
TI  - Blockade of p38 mitogen-activated protein kinase and TGF-beta1/Smad signaling
      pathways rescues bone marrow-derived peritubular capillary endothelial cells in
      adriamycin-induced nephrosis.
AB  - The peritubular capillary (PTC) network is a component of the tubulointerstitium
      of the kidney with important roles in renal function and hemodynamics. Bone
      marrow (BM)-derived cells can contribute to repair of the renal PTC network after
      ischemic injury. However, the cell fate and the regulation of renal BM-derived
      cell engraftment in comparison with somatic cells during disease progression are
      unclear. This study characterized the time course and regulation of PTC
      endothelial cell injury in adriamycin (ADR)-induced nephropathy in mice, a model
      of chronic, irreversible, progressive renal disease. Enhanced green fluorescence
      protein-positive BM cells that coexpressed two endothelial cell markers, von
      Willebrand factor and CD31, were found to engraft into the PTC of chimeric ADR
      injected mice in a time-dependent manner. The number of BM-derived PTC
      endothelial cells peaked 2 wk after ADR injection, then declined dramatically
      thereafter. In these mice, apoptosis was evident in BM-derived PTC endothelial
      cells, and the p38 mitogen-activated protein kinase (MAPK) and TGF-beta1/Smad
      signaling pathways were activated. Blocking both the p38 MAPK and TGF-beta1/Smad
      signaling pathways by administration of a p38 MAPK inhibitor (SB203580) and a TGF
      beta receptor 1 inhibitor (ALK5I) to ADR-injected mice rescued BM-derived PTC
      endothelial cells from apoptosis, reduced the loss of PTC, and restored kidney
      function. Investigation into the signaling pathways that regulate the
      differentiation and survival of BM-derived cells that engraft into the kidney in
      the proinflammatory setting of progressive renal disease is vital for the
      successful development of cell-based therapies to promote renal regeneration and
      repair.

PMID- 16959827
TI  - Risks for end-stage renal disease, cardiovascular events, and death in Hispanic
      versus non-Hispanic white adults with chronic kidney disease.
AB  - Rates of ESRD are rising faster in Hispanic than non-Hispanic white individuals,
      but reasons for this are unclear. Whether rates of cardiovascular events and
      mortality differ among Hispanic and non-Hispanic white patients with chronic
      kidney disease (CKD) also is not well understood. Therefore, this study examined
      the associations between Hispanic ethnicity and risks for ESRD, cardiovascular
      events, and death in patients with CKD. A total of 39,550 patients with stages 3
      to 4 CKD from Kaiser Permanente of Northern California were included. Hispanic
      ethnicity was obtained from self-report supplemented by surname matching. GFR was
      estimated from the abbreviated Modification of Diet in Renal Disease equation,
      and clinical outcomes, patient characteristics, and longitudinal medication use
      were ascertained from health plan databases and state mortality files. After
      adjustment for sociodemographic characteristics, Hispanic ethnicity was
      associated with an increased risk for ESRD (hazard ratio [HR] 1.93; 95%
      confidence interval [CI] 1.72 to 2.17) when compared with non-Hispanic white
      patients, which was attenuated after controlling for diabetes and insulin use (HR
      1.50; 95% CI 1.33 to 1.69). After further adjustment for potential confounders,
      Hispanic ethnicity remained independently associated with an increased risk for
      ESRD (HR 1.33; 95% CI 1.17 to 1.52) as well as a lower risk for cardiovascular
      events (HR 0.82; 95% CI 0.76 to 0.88) and death (HR 0.72; 95% CI 0.66 to 0.79).
      Among a large cohort of patients with CKD, Hispanic ethnicity was associated with
      lower rates of death and cardiovascular events and a higher rate of progression
      to ESRD. The higher prevalence of diabetes among Hispanic patients only partially
      explained the increased risk for ESRD. Further studies are required to elucidate
      the cause(s) of ethnic disparities in CKD-associated outcomes.

PMID- 16959828
TI  - Baseline predictors of renal disease progression in the African American Study of
      Hypertension and Kidney Disease.
AB  - Patients with chronic kidney disease have an increased risk for progression to
      ESRD. The purpose of this study was to examine factors that predict increased
      risk for adverse renal outcomes. Cox regression was performed to assess the
      potential of 38 baseline risk factors to predict the clinical renal composite
      outcome of 50% or 25-ml/min per 1.73 m(2) GFR decline or ESRD among 1094 black
      patients with hypertensive nephrosclerosis (GFR 20 to 65 ml/min per 1.73 m(2)).
      Patients were trial participants who had been randomly assigned to one of two BP
      goals and to one of three antihypertensive regimens and followed for a range of 3
      to 6.4 yr. In unadjusted and adjusted analyses, baseline proteinuria was
      consistently associated with an increased risk for adverse renal outcomes, even
      at low levels of proteinuria. The relationship of proteinuria with adverse renal
      outcomes also was evident in analyses that were stratified by level of GFR, which
      itself was associated with adverse renal outcomes but only at levels <40 ml/min.
      Other factors that were significantly associated with increased renal events
      after adjustment for baseline GFR, age, and gender, both with and without
      adjustment for baseline proteinuria, included serum creatinine, urea nitrogen,
      and phosphorus. In black patients with hypertensive nephrosclerosis, increased
      proteinuria, reduced GFR, and elevated levels of serum creatinine, urea nitrogen
      and phosphorus were directly associated with adverse clinical renal events. These
      findings identify a subset of this high-risk population that might benefit from
      even more aggressive treatment.

PMID- 16959829
TI  - Downregulation of SnoN expression in obstructive nephropathy is mediated by an
      enhanced ubiquitin-dependent degradation.
AB  - Smad transcriptional co-repressor SnoN acts as an antagonist that tightly
      controls the trans-activation of TGF-beta/Smad target genes. SnoN protein is
      reduced progressively in the fibrotic kidney after obstructive injury, suggesting
      that the loss of Smad antagonist is a critical event that leads to an
      uncontrolled fibrogenic signaling. However, the mechanism underlying SnoN
      downregulation remains unknown. This study investigated the regulation and
      mechanism of renal SnoN expression in vivo. Whereas SnoN protein was markedly
      diminished, its mRNA levels remained relatively constant in the obstructed kidney
      after ureteral ligation. An increased ubiquitination and proteasome-dependent
      degradation of SnoN was found in obstructed kidney, compared with sham controls.
      Smad ubiquitination regulatory factor-2, an E3 ubiquitin ligase, was induced and
      formed a complex with SnoN in vivo. In vitro, TGF-beta1 promoted SnoN protein
      degradation, which was mediated by ubiquitination and a proteasome-dependent
      mechanism. SnoN constitutively interacted with another Smad co-repressor, Ski,
      and they formed ternary complex with Smad2/3 upon TGF-beta1 stimulation. However,
      ectopic expression of Ski did not alter the degradation rate of SnoN. Blockage of
      SnoN degradation by proteasome inhibitor abolished TGF-beta1-mediated alpha
      smooth muscle actin and fibronectin induction, suggesting that SnoN degradation
      could be necessary for TGF-beta1 to exert its fibrogenic action. Furthermore,
      knockdown of Smad ubiquitination regulatory factor-2 expression by small
      interfering RNA strategy led to an increase in SnoN abundance and inhibited the
      TGF-beta1-mediated gene transcription. These results indicate that downregulation
      of SnoN expression in the obstructed kidney is mediated by an enhanced ubiquitin
      dependent degradation. Preservation of SnoN by inhibiting its degradation may be
      a novel strategy for targeting hyperactive Smad signaling in renal fibrotic
      diseases.

PMID- 16959831
TI  - Sex difference in the suppressive effect of cortisol on pulsatile secretion of
      luteinizing hormone in sheep.
AB  - We tested the hypothesis that there are sex differences in the inhibitory effect
      of cortisol on pulsatile LH secretion and pituitary responsiveness to GnRH in
      gonadectomized sheep. In experiment 1, pulsatile LH secretion was examined in
      gonadectomized ewes and rams infused with either saline, a low (250 microg/kg.h)
      or a high (500 microg/kg.h) dose of cortisol for 30 h. In experiment 2, direct
      pituitary actions of cortisol were assessed by monitoring LH pulse amplitude in
      response to exogenous GnRH in hypothalamo-pituitary disconnected ewes and rams
      infused with the low dose of cortisol. In experiment 1, the mean (+/-sem) plasma
      LH concentration was (P<0.05) reduced significantly during cortisol infusion in
      both sexes, but the effect was greater in rams. In ewes, LH pulse amplitude and
      frequency were reduced (P<0.05) at the high, but not the low, cortisol dose,
      whereas total LH output (LH pulse amplitude multiplied by frequency) was reduced
      (P<0.05) at both doses. In rams, LH pulse frequency and amplitude and total LH
      output were (P<0.05) reduced significantly at both cortisol doses. In experiment
      2, plasma LH concentration and pulse amplitude in response to exogenous GnRH were
      not affected by infusion of cortisol in either sex. We conclude that
      gonadectomized rams are more sensitive than gonadectomized ewes to the effects of
      cortisol to inhibit LH secretion and that sex differences exist in the specific
      actions of cortisol on LH pulses. The results of experiment 2 suggest that intact
      hypothalamic input to the pituitary is necessary for cortisol to inhibit
      pituitary responsiveness to GnRH.

PMID- 16959830
TI  - A comparative study of the central effects of specific proopiomelancortin (POMC)
      derived melanocortin peptides on food intake and body weight in pomc null mice.
AB  - Functional disruption of either MC3R or MC4R results in obesity, implicating both
      in the control of energy homeostasis. The ligands for these receptors are derived
      from the prohormone proopiomelancortin (POMC), which is posttranslationally
      processed to produce a set of melanocortin peptides with a range of activities at
      the MC3R and MC4R. The relative importance of each of these peptides alpha-MSH,
      gamma3-MSH, gamma2-MSH, gamma-lipotropin (gamma-LPH) and, in man but not in
      rodents, beta-MSH] in the maintenance of energy homeostasis is, as yet, unclear.
      To investigate this further, equimolar amounts (2 nmol) of each peptide were
      centrally administered to freely feeding, corticosterone-supplemented, Pomc null
      (Pomc-/-) mice. After a single dose at the onset of the dark cycle, alpha-MSH had
      the most potent anorexigenic effect, reducing food intake to 35% of sham-treated
      animals. beta-MSH, gamma-LPH, and gamma3- and gamma2-MSH all reduced food intake
      but to a lesser degree. The effects of peptide administration over 3 d were also
      assessed. Only alpha-MSH significantly reduced body weight, affecting both fat
      and lean mass. Other peptides had no significant effect on body weight. Pair
      feeding of sham-treated mice to those treated with alpha-MSH resulted in
      identical changes in total weight, fat and lean mass indicating that the effects
      of alpha-MSH were primarily due to reduced food intake rather than increased
      energy expenditure. Although other melanocortins can reduce food intake in the
      short-term, only alpha-MSH can reduce the excess fat and lean mass found in Pomc
      /- mice, mediated largely through an effect on food intake.

PMID- 16959832
TI  - Life-long suppression of growth hormone-insulin-like growth factor I activity in
      genetically altered rats could prevent age-related renal damage.
AB  - To determine whether life-long reduction in the GH/IGF-I activity could be
      renoprotective and attenuate renal damage, we examined the kidneys of transgenic
      strain of rats whose GH gene was suppressed by an antisense GH transgene. Male
      rats homozygote for the transgene (tg/tg) had a reduced number of pituitary GH
      secreting cells, and 53% less plasma concentration of IGF-I, compared with wild
      type (wt/wt) rats at 6 months of age. We compared the kidneys obtained from male
      wild-type young (6 months) and old (24 months) rats with male homozygote
      transgenic young (6 months) and old (24 months) rats. The wild-type rats showed
      features of renal damage as they grew older, including glomerulosclerosis (higher
      sclerosis index at 24 months; P<0.0001), tubulointerstitial widening (increased
      interstitial volume at 24 months; P<0.0001), and presence of phenotypically
      altered myofibroblasts and increased accumulation of collagens. Life-long
      suppression of GH/IGF-I activity resulted in prevention of age-associated renal
      diseases in homozygote transgenic rats at 24 months (sclerosis index: 1.65+/-0.11
      in wild-type vs. 0.463+/-0.061 in transgenic rats; interstitial volume: 34.2+/
      0.82 in wild-type vs. 12.8+/-0.32 in homozygote transgenic rats at 24 months;
      P<0.0001). Such reno-protective effects in transgenic rats were associated with
      decreased renal accumulation of ED-1-positive macrophages, and less renal
      expression of pro-fibrogenic factors, including connective tissue growth factor
      and heat shock protein 47. Our in vivo genetic manipulation study provides direct
      evidence of reno-protective effects of life-long suppression of GH/IGF-I system,
      by reducing renal infiltration of inflammatory cells, and by suppressing the
      synthesis of profibrogenic factors and accumulation of extracellular matrix
      protein.

PMID- 16959833
TI  - GPR39 signaling is stimulated by zinc ions but not by obestatin.
AB  - GPR39 is an orphan member of the ghrelin receptor family that recently was
      suggested to be the receptor for obestatin, a peptide derived from the ghrelin
      precursor. Here, we compare the effect of obestatin to the effect of Zn(2+) on
      signal transduction and study the effect of obestatin on food intake. Although
      Zn(2+) stimulated inositol phosphate turnover, cAMP production, arrestin
      mobilization, as well as cAMP response element-dependent and serum response
      element-dependent transcriptional activity in GPR39-expressing cells as opposed
      to mock-transfected cells, no reproducible effect was obtained with obestatin in
      the GPR39-expressing cells. Moreover, no specific binding of obestatin could be
      detected in two different types of GPR39-expressing cells using three different
      radioiodinated forms of obestatin. By quantitative PCR analysis, GPR39 expression
      was readily detected in peripheral organs such as duodenum and kidney but not in
      the pituitary and hypothalamus, i.e. presumed central target organs for
      obestatin. Obestatin had no significant and reproducible effect on acute food
      intake in either freely fed or fasted lean mice. It is concluded that GPR39 is
      probably not the obestatin receptor. In contrast, the potency and efficacy of
      Zn(2+) in respect of activating signaling indicates that this metal ion could be
      a physiologically relevant agonist or modulator of GPR39.

PMID- 16959834
TI  - Structural insights into autoreactive determinants in thyroid peroxidase composed
      of discontinuous and multiple key contact amino acid residues contributing to
      epitopes recognized by patients' autoantibodies.
AB  - Thyroid peroxidase (TPO) is a major autoantigen of thyroid autoimmune disease,
      and the autoantibodies that are produced recognize two immunodominant regions
      (IDR) of the molecule, termed IDR-A and -B. Based upon our structural model of
      the TPO ectodomain, we recently identified R225 and K627 as key residues in IDR-A
      and -B, respectively. We report here on rational mutagenic investigations to
      identify additional residues surrounding R225 and K627 that affect the binding of
      recombinant human Fabs (rhFabs) specific for each IDR. Two residues R646 and D707
      were identified from the model as promising surface-exposed amino acids adjacent
      to R225. Similarly, residues E604, D620, D624, and D630 were identified in the
      vicinity of K627. These residues were substituted in different combinations of
      single, double, and multiple mutations, and stably expressed in Chinese hamster
      ovary cells. By fluorescence-activated cell sorting and capture ELISA, we found
      that R225A, R646A, and D707N specifically led to the loss of binding of IDR-A
      rhFabs, whereas E604A, D620R, K627G, and D630N specifically abrogated the binding
      of IDR-B rhFabs. Further supportive evidence of the importance of these residues
      for the IDR epitopes was obtained with patients' sera. We conclude that R646 and
      D707 together with R225 constitute a functional epitope within IDR-A, and that
      residues E604, D620, and D630, together with K627, constitute a functional
      epitope within IDR-B. This identification of key residues within the autoreactive
      epitopes will help in understanding the structural basis for the breakdown of
      immune tolerance to TPO in thyroid autoimmune disease.

PMID- 16959835
TI  - Glucocorticoids prevent the normal increase in placental vascular endothelial
      growth factor expression and placental vascularity during late pregnancy in the
      rat.
AB  - Increased glucocorticoid exposure reduces fetal growth and predisposes to an
      increased risk of disease in later life. In addition to direct effects on fetal
      growth, glucocorticoids also compromise fetal growth indirectly via detrimental
      effects on placental growth and function. The current study investigated the
      effects of dexamethasone-induced intrauterine growth restriction on placental
      vascular development and expression of the endothelial cell-specific mitogen,
      vascular endothelial growth factor (VEGF). Separate analyses were conducted for
      the three main VEGF isoforms (VEGF120, VEGF164, and VEGF188) in the two
      functionally and morphologically distinct regions of the rat placenta, the basal
      and labyrinth zones. Quantitative PCR and immunohistochemical analysis
      demonstrated that expression of VEGF was markedly up-regulated specifically in
      the rapidly growing labyrinth zone over the final third of normal pregnancy.
      Unbiased stereological analyses showed an associated increase in the volume and
      surface area of maternal and fetal blood spaces, including vascular remodeling of
      the fetal capillary network near term. In contrast, dexamethasone-induced fetal
      and placental growth restriction reduced expression of the Vegf120 and Vegf188
      isoforms and prevented normal labyrinthine vascular development near term. Most
      notably, dexamethasone impaired the normal increase in fetal vessel density over
      the final third of pregnancy, with no effect on the density of maternal blood
      spaces. Overall, this study quantifies the labyrinth zone-specific increases in
      placental VEGF expression and vascular development during normal pregnancy, and
      shows that these increases are prevented by maternal dexamethasone treatment. Our
      data suggest that glucocorticoid-induced restriction of fetal and placental
      growth is mediated, in part, via inhibition of placental VEGF expression and an
      associated reduction in placental vascularization.

PMID- 16959836
TI  - Brainstem thyrotropin-releasing hormone regulates food intake through vagal
      dependent cholinergic stimulation of ghrelin secretion.
AB  - The brainstem is essential for mediating energetic response to starvation. Brain
      stem TRH is synthesized in caudal raphe nuclei innervating brainstem and spinal
      vagal and sympathetic motor neurons. Intracisternal injection (ic) of a stable
      TRH analog RX77368 (7.5-25 ng) dose-dependently stimulated solid food intake by
      2.4- to 3-fold in freely fed rats, an effect that lasted for 3 h. By contrast,
      RX77368 at 25 ng injected into the lateral ventricle induced a delayed and
      insignificant orexigenic effect only in the first hour. In pentobarbital
      anesthetized rats, RX77368 (50 ng) ic induced a significant bipeak increase in
      serum total ghrelin levels from the basal of 8.7+/-1.7 ng/ml to 13.4+/-2.4 ng/ml
      at 30 min and 14.5+/-2.0 ng/ml at 90 min, which was prevented by either bilateral
      vagotomy (-60 min) or atropine pretreatment (2 mg/kg, -30 min) but magnified by
      bilateral adrenalectomy (-60 min). TRH analog ic-induced food intake in freely
      fed rats was abolished by either peripheral atropine or ghrelin receptor
      antagonist (D-Lys-3)-GHRP-6 (10 micromol/kg) or ic Y1 receptor antagonist 122PU91
      (10 nmol/5 microl). Brain stem TRH mRNA and TRH receptor 1 mRNA increased by 57
      58 and 33-35% in 24- and 48-h fasted rats and returned to the fed levels after a
      3-h refeeding. Natural food intake in overnight fasted rats was significantly
      reduced by ic TRH antibody, ic Y1 antagonist, and peripheral atropine. These data
      establish a physiological role of brainstem TRH in vagal-ghrelin-mediated
      stimulation of food intake, which involves interaction with brainstem Y1
      receptors.

PMID- 16959837
TI  - Postnatal development of kisspeptin neurons in mouse hypothalamus; sexual
      dimorphism and projections to gonadotropin-releasing hormone neurons.
AB  - The neuropeptide kisspeptin has recently been implicated as having a critical
      role in the activation of the GnRH neurons to bring about puberty. We examined
      here the postnatal development of kisspeptin neuronal populations and their
      projections to GnRH neurons in the mouse. Three populations of kisspeptin neurons
      located in the 1) anteroventral periventricular nucleus (AVPV) and the preoptic
      periventricular nucleus (PeN), 2) dorsomedial hypothalamus, and 3) arcuate
      nucleus were identified using an antisera raised against mouse kisspeptin-10. A
      marked 10-fold (P<0.01), female-dominant sex difference in the numbers of
      kisspeptin neurons existed in the AVPV/PeN but not elsewhere. Kisspeptin neurons
      in the AVPV/PeN of both sexes displayed a similar pattern of postnatal
      development with no cells detected at postnatal day (P) 10, followed by increases
      from P25 to reach adult levels by puberty onset (P<0.01; P31 females and P45
      males). This pattern was not found in the dorsomedial hypothalamus or arcuate
      nucleus. Dual immunofluorescence experiments demonstrated close appositions
      between kisspeptin fibers and GnRH neuron cell bodies that were first apparent at
      P25 and increased across postnatal development in both sexes. These studies
      demonstrate kisspeptin peptide expression in the mouse hypothalamus and reveal
      the postnatal development of a sexually dimorphic continuum of kisspeptin neurons
      within the AVPV and PeN. This periventricular population of kisspeptin neurons
      reaches adult-like proportions at the time of puberty onset and is the likely
      source of the kisspeptin inputs to GnRH neurons.

PMID- 16959838
TI  - Role for prostaglandins in the regulation of type 1 11beta-hydroxysteroid
      dehydrogenase in human granulosa-lutein cells.
AB  - 11beta-hydroxysteroid dehydrogenase (11betaHSD) enzymes regulate glucocorticoid
      availability in target tissues. 11betaHSD1 is the predominant isoenzyme expressed
      and active in human granulosa-lutein (hGL) cells. This study investigated the
      effects of pharmacological inhibitors of prostaglandin (PG) synthesis on
      11betaHSD1 activities and expression in hGL cells. The consequences for
      11betaHSD1 of increasing exposure of hGL cells to PGs, either by treatment with
      exogenous PGs or by challenging cells with IL-1beta, were also assessed.
      Suppression of basal PG synthesis using four different inhibitors of PG H
      synthase enzymes [indomethacin, niflumic acid, meclofenamic acid (MA) and N-(2
      cyclohexyloxy-4-nitorophenyl) methane sulfonamide (NS-398)] each resulted in
      significant decreases in both cortisol oxidation and cortisone reduction. Both
      activities of 11betaHSD1 were suppressed by up to 64+/-6% (P<0.05). Over 4 and 24
      h, neither MA nor NS-398 affected the expression of 11betaHSD1 protein,
      suggesting enzyme regulation by PGs at the posttranslational level. When cells
      were cotreated for 4 h with PGHS inhibitors plus 30 nm PGD2, PGF2alpha, or PGE2,
      each PG overcame the suppression of cortisol oxidation by indomethacin or MA.
      Treatment of hGL cells with IL-1beta increased the concentrations of both PGE2
      and PGF2alpha, accompanied by a 70+/-25% increase in net cortisol oxidation. All
      three responses to IL-1beta were abolished when cells were cotreated with MA.
      These findings suggest a role for PGs in the posttranslational regulation of
      11betaHSD1 activities in hGL cells.

PMID- 16959839
TI  - Developmental control of iodothyronine deiodinases by cortisol in the ovine fetus
      and placenta near term.
AB  - Preterm infants have low serum T4 and T3 levels, which may partly explain the
      immaturity of their tissues. Deiodinase enzymes are important in determining the
      bioavailability of thyroid hormones: deiodinases D1 and D2 convert T4 to T3,
      whereas deiodinase D3 inactivates T3 and produces rT3 from T4. In human and ovine
      fetuses, plasma T3 rises near term in association with the prepartum cortisol
      surge. This study investigated the developmental effects of cortisol and T3 on
      tissue deiodinases and plasma thyroid hormones in fetal sheep during late
      gestation. Plasma cortisol and T3 concentrations in utero were manipulated by
      exogenous hormone infusion and fetal adrenalectomy. Between 130 and 144 d of
      gestation (term 145+/-2 d), maturational increments in plasma cortisol and T3,
      and D1 (hepatic, renal, perirenal adipose tissue) and D3 (cerebral), and
      decrements in renal and placental D3 activities were abolished by fetal
      adrenalectomy. Between 125 and 130 d, iv cortisol infusion raised hepatic, renal,
      and perirenal adipose tissue D1 and reduced renal and placental D3 activities.
      Infusion with T3 alone increased hepatic D1 and decreased renal D3 activities.
      Therefore, in the sheep fetus, the prepartum cortisol surge induces tissue
      specific changes in deiodinase activity that, by promoting production and
      suppressing clearance of T3, may be responsible for the rise in plasma T3
      concentration near term. Some of the maturational effects of cortisol on
      deiodinase activity may be mediated by T3.

PMID- 16959840
TI  - Selenium-dependent pre- and posttranscriptional mechanisms are responsible for
      sexual dimorphic expression of selenoproteins in murine tissues.
AB  - Important enzymes for thyroid hormone metabolism, antioxidative defense, and
      intracellular redox control contain selenocysteine (Sec) in their active centers.
      Expression of these selenoproteins is tightly controlled, and a sex-specific
      phenotype is observed on disturbance of selenium (Se) transport in mice.
      Therefore, we analyzed Se concentrations and expression levels of several
      selenoproteins including type I iodothyronine deiodinase (Dio1) and glutathione
      peroxidase (GPx) isozymes in male and female mice. On regular lab chow, serum Se
      levels were comparable, but serum GPx3 activity was higher in females than males
      (1.3-fold). Selenoprotein P (SePP) mRNA levels were higher in livers (1.3-fold)
      and lower in kidneys (to 31%) in female compared with male mice. Orchidectomy
      alleviated the sex-specific differences in SePP mRNA amounts, indicating
      modulatory effects of androgens on SePP expression. Female mice expressed higher
      levels of Dio1 mRNA in kidney (2.6-fold) and liver (1.4-fold) in comparison with
      male mice. This sexual dimorphic expression of Dio1 mRNA was paralleled by
      increased Dio1 activity in female kidney (1.8-fold) but not in liver in which
      males expressed higher Dio1 activity (2.8-fold). Interestingly, Se deficiency
      decreased Dio1 activity more effectively in males than females, and resulting
      hepatic enzyme levels were then comparable between the sexes. At the same time,
      the sex-specific difference of Dio1 activity widened in kidney. Orchidectomy or
      estradiol treatment of ovariectomized females impacted stronger on renal than
      hepatic Dio1 expression. Thus, we conclude that Se-dependent posttranscriptional
      mechanisms are operational that affect either translational efficiency or Dio1
      stability in a sex- and tissue-specific manner.

PMID- 16959841
TI  - Transcript profiling of the androgen signal in normal prostate, benign prostatic
      hyperplasia, and prostate cancer.
AB  - Human prostate adenocarcinoma (CaP) and benign prostatic hyperplasia (BPH) have
      epithelial and stromal cell origins, respectively. To determine whether the
      androgen signal is processed differently in these cell types the expression of
      transcripts for enzymes that control ligand access to the androgen receptor (AR)
      were measured. Transcripts for type 2 5alpha-reductase, ketosteroid reductases
      [aldo-keto reductase (AKR)1C1-AKR1C4], the major oxidative 3alpha-hydroxysteroid
      dehydrogenase (HSD) retinol dehydrogenase (RODH)-like 3alpha-HSD (RL-HSD) and
      nuclear receptors [AR, estrogen receptor (ER)alpha, and ERbeta] were determined
      in whole human prostate and in cultures of primary epithelial cells (PEC) and
      primary stromal cells (PSC) from normal prostate, CaP and BPH by real-time RT
      PCR. Normal PEC (n=14) had higher levels of AKR1C1 (10-fold, P<0.001), AKR1C2
      (115-fold, P<0.001) and AKR1C3 (6-fold, P<0.001) than normal PSC (n=15),
      suggesting that reductive androgen metabolism occurs. By contrast, normal PSC had
      higher levels of AR (8-fold, P<0.001) and RL-HSD (21-fold, P<0.001) than normal
      PEC, suggesting that 3alpha-androstanediol is converted to 5alpha
      dihydrotestosterone to activate AR. In CaP PEC (n=14), no significant changes in
      transcript levels vs. normal PEC were observed. In BPH PSC (n=21) transcripts for
      AR (2-fold, P<0.001), AKR1C1 (4-fold, P<0.001), AKR1C2 (10-fold P<0.001), AKR1C3
      (4-fold, P<0.001) and RL-HSD (3-fold, P<0.003) were elevated to increase androgen
      response. Differences in the AR:ERbeta transcript ratios (eight in normal PEC vs.
      280 in normal PSC) were maintained in PEC and PSC in diseased prostate. These
      data suggest that CaP may be more responsive to an ERbeta agonist and BPH may be
      more responsive to androgen ablation.

PMID- 16959842
TI  - Igf2 deficiency results in delayed lung development at the end of gestation.
AB  - IGF-II is a polypeptide hormone with structural homology to insulin and IGF-I.
      IGF-II plays an important role in fetal growth as mice with targeted disruption
      of the IGF-II gene (Igf2) exhibit severe growth retardation. The role of IGFs in
      the fetal lung has been suggested by several studies, including those that have
      identified IGF mRNA expression, and that of their receptors and binding proteins
      in the lungs at different stages of development. In this study, we used mice
      carrying a null mutation of Igf2 (Igf2-/- mice) to determine whether the absence
      of IGF-II had any effect in fetal lung maturation. Our results showed that the
      lungs of Igf2-/- fetuses had thicker alveolar septae and poorly organized alveoli
      when compared with those of Igf2+/+ on d 17.5 and 18.5 of gestation. These
      morphological alterations may be the result of exposure to lower levels of
      glucocorticoids because plasma corticosterone levels were significantly lower in
      Igf2-/- mothers compared with wild-type controls. In support of this, fetuses
      from homozygous knockout matings, where mothers were treated with 15 microg/ml
      corticosterone, and Igf2-/- fetuses obtained from heterozygous matings had
      similar lung histology to those of wild-type fetuses. Finally, we found that IGF
      I and SP-B mRNA levels were up-regulated in the lungs of Igf2-/- fetuses at the
      end of gestation. This study suggests that Igf2 plays an important role in the
      development of the fetal lung and may affect fetal lung maturation by regulating
      maternal factors, such as corticosterone levels, during pregnancy.

PMID- 16959843
TI  - Targeted disruption of the pregnancy-associated plasma protein-A gene is
      associated with diminished smooth muscle cell response to insulin-like growth
      factor-I and resistance to neointimal hyperplasia after vascular injury.
AB  - IGF-I is an important determinant of the vascular response to injury in large
      part through its ability to stimulate migration and proliferation of smooth
      muscle cells (SMCs). In this study, we used mice with targeted disruption of the
      pregnancy-associated plasma protein-A gene (PAPP-A-/-) and wild-type (WT)
      littermates to test the hypotheses that PAPP-A, a metalloproteinase that cleaves
      inhibitory IGF binding protein (IGFBP)-4, regulates vascular SMC responses to IGF
      I in vitro and is critical for the development of vascular neointima after injury
      in vivo. Vascular SMCs from PAPP-A-/- mice lacked IGFBP-4 protease activity and
      failed to respond to treatment with IGF-I in the presence of IGFBP-4, whereas
      SMCs from WT mice with robust IGFBP-4 protease activity showed significant
      migratory and proliferative responses to IGF-I/IGFBP-4. For in vivo testing, PAPP
      A-/- and WT mice underwent unilateral carotid ligation, a model of injury-induced
      neointimal hyperplasia. In WT mice, PAPP-A mRNA expression was markedly elevated
      7 and 14 d after carotid ligation, associated with a progressive increase in
      neointimal hyperplasia and, in many cases, with complete occlusion of the vessel
      at 28 d. In contrast, PAPP-A-/- mice showed little evidence of progression
      resulting in a 75% reduction in neointimal area when compared with WT at 28 d.
      Cells staining for proliferating cell nuclear antigen were plentiful in the SMC
      rich medial and neointimal areas of the injured WT vessel in stark contrast to
      the relatively few proliferating cells in the same areas of the PAPP-A-/- vessel.
      Expression of IGF-I and IGFBP-4 was similarly elevated in injured carotids from
      WT and PAPP-A-/- mice with no change in IGF-I receptor expression. IGFBP-5, an
      IGF-responsive gene, was increased 2-fold in WT but not in PAPP-A-/- carotids,
      suggesting reduced IGF activity in the absence of PAPP-A. Thus, PAPP-A-deficient
      mice are resistant to neointimal formation after injury, which may be explained
      in part by the ability of PAPP-A to enhance local IGF-I stimulation of vascular
      SMCs through proteolysis of IGFBP-4.

PMID- 16959844
TI  - BRAFV600E promotes invasiveness of thyroid cancer cells through nuclear factor
      kappaB activation.
AB  - The BRAFV600E mutation is closely linked to tumorigenesis and malignant phenotype
      of papillary thyroid cancer. Signaling pathways activated by BRAFV600E are still
      unclear except a common activation pathway, MAPK cascade. To investigate the
      possible target of BRAFV600E, we developed two different cell culture models: 1)
      doxycycline-inducible BRAFV600E-expressing clonal line derived from human thyroid
      cancer WRO cells originally harboring wild-type BRAF; 2) WRO, KTC-3, and NPA
      cells infected with an adenovirus vector carrying BRAFV600E. BRAFV600E expression
      induced ERK phosphorylation and cyclin D1 expression in these cells. The
      BRAFV600E-overexpressing cells also showed an increase of nuclear factor kappaB
      (NF-kappaB) DNA-binding activity, resulting in up-regulation of antiapoptotic c
      IAP-1, c-IAP-2, and X-linked inhibitor of apoptosis. Furthermore, BRAFV600E
      expression also induced the expression of matrix metalloproteinase and cell
      invasion into matrigel through NF-kappaB pathway. Increased invasive ability by
      BRAFV600E expression was significantly inhibited by a specific NF-kappaB
      inhibitor, racemic dehydroxymethylepoxyquinomicin. These data indicate that
      BRAFV600E activates not only MAPK but also NF-kappaB signaling pathway in human
      thyroid cancer cells, leading to an acquisition of apoptotic resistance and
      promotion of invasion. Inactivation of NF-kappaB may provide a new therapeutic
      modality for thyroid cancers with BRAFV600E.

PMID- 16959845
TI  - Genistein affects adipose tissue deposition in a dose-dependent and gender
      specific manner.
AB  - The soy isoflavone genistein targets adipose tissue and elicits physiological
      effects that may vary based on dietary intake. We hypothesized that the adipose
      effects of genistein are dose and gender dependent. Four-week-old C57BL/6 male
      and female mice received daily oral doses of genistein (50-200,000 microg/kg.d)
      or 17beta-estradiol (E2) (5 microg/kg.d) for 15 d or a diet containing 800 ppm
      genistein. Genistein increased epididymal and renal fat pad and adipocyte size at
      doses up to 50,000 microg/kg.d or at 800 ppm in the diet in males but not in
      females. The alteration in adipocity correlated with changes in peripheral
      insulin resistance. These treatments increased genistein serum concentrations
      from 35+/-6 to 103+/-26 nM 12 h after treatment and lowered plasma triglycerides
      and cholesterol levels. The 200,000 microg/kg.d genistein dose decreased adipose
      tissue weight similarly to E2. This genistein dose down-regulated estrogen
      receptor (beta more than alpha) and progesterone receptor expression and induced
      estrogen-dependent adipose differentiation factors; it did not change expression
      of the minimal consensus estrogen-responsive element in ERE-tK-LUC mice, which
      was positively modulated in other tissues (e.g. the lung). E2 down-regulated
      almost all examined adipogenic factors. Gene microarray analysis identified
      factors in fat metabolism and obesity-related phenotypes differentially regulated
      by low and high doses of genistein, uncovering its adipogenic and antiadipogenic
      actions. The lower dose induced the phospholipase A2 group 7 and the phospholipid
      transfer protein genes; the 200,000 microg/kg.d dose inhibited them. The
      antiadipogenic action of genistein and down-regulation of adipogenic genes
      required the expression of ERbeta. In conclusion, nutritional doses of genistein
      are adipogenic in a gender-specific manner, whereas pharmacological doses
      inhibited adipose deposition.

PMID- 16959846
TI  - Increased tumor growth in mice with diet-induced obesity: impact of ovarian
      hormones.
AB  - Obesity increases the risk of many cancers in both males and females. This study
      describes a link between obesity, obesity-associated metabolic alterations, and
      the risk of developing cancer in male and female mice. The goal of this study was
      to evaluate the relationship between gender and obesity and to determine the role
      of estrogen status in obese females and its effect on tumor growth. We examined
      the susceptibility of C57BL/6 mice to diet-induced obesity, insulin
      resistance/glucose intolerance, and tumors. Mice were injected sc with one of two
      tumorigenic cell lines, Lewis lung carcinoma, or mouse colon 38-adenocarcinoma.
      Results show that tumor growth rate was increased in obese mice vs. control mice
      irrespective of the tumor cell type. To investigate the effect of estrogen status
      on tumor development in obese females, we compared metabolic parameters and tumor
      growth in ovariectomized (ovx) and intact obese female mice. Obese ovx female
      mice developed insulin resistance and glucose intolerance similar to that
      observed in obese males. Our results demonstrate that body adiposity increased in
      ovx females irrespective of the diet administered and that tumor growth
      correlated positively with body adiposity. Overall, these data point to more
      rapid tumor growth in obese mice and suggest that endogenous sex steroids,
      together with diet, affect adiposity, insulin sensitivity, and tumor growth in
      female mice.

PMID- 16959847
TI  - Endothelin-1 inhibits apoptosis through a sphingosine kinase 1-dependent
      mechanism in uterine leiomyoma ELT3 cells.
AB  - Uterine leiomyomas, or fibroids, are the most common tumors of the myometrium.
      The ELT3 cell line, derived from Eker rat leiomyoma, has been successfully used
      as a model for the study of leiomyomas. We have demonstrated previously the
      potent mitogenic properties of the peptidic hormone endothelin (ET)-1 in this
      cell line. Here we investigated the antiapoptotic effect of ET-1 in ELT3 cells.
      We found that 1) serum starvation of ELT3 cells induced an apoptotic process
      characterized by cytochrome c release from mitochondria, caspase-3/7 activation,
      nuclei condensation and DNA fragmentation; 2) ET-1 prevented the apoptotic
      process; and 3) this effect of ET-1 was fully reproduced by ETB agonists. In
      contrast, no antiapoptotic effect of ET-1 was observed in normal myometrial
      cells. A pharmacological approach showed that the effect of ET-1 on caspase-3/7
      activation in ELT3 cells was not dependent on phosphatidylinositol 3-kinase,
      ERK1/2, or phospholipase D activities. However, inhibitors of sphingosine kinase
      1 (SphK1), dimethylsphingosine and threo-dihydrosphingosine, reduced the effect
      of ET-1 by about 50%. Identical results were obtained when SphK1 expression was
      down-regulated in ELT3 cells transfected with SphK1 small interfering RNA.
      Furthermore, serum starvation induced a decrease in SphK1 activity that was
      prevented by ET-1 without affecting the level of SphK1 protein expression.
      Finally, sphingosine 1-phosphate, the product of SphK activity, was as efficient
      as ET-1 in inhibiting serum starvation-induced caspase-3/7 activation. Together,
      these results demonstrate that ET-1 possesses a potent antiapoptotic effect in
      ELT3 cells that involves sphingolipid metabolism through the activation of SphK1.

PMID- 16959848
TI  - Beta3-adrenergic receptors stimulate glucose uptake in brown adipocytes by two
      mechanisms independently of glucose transporter 4 translocation.
AB  - To identify the mechanisms whereby norepinephrine induces glucose uptake in brown
      adipose tissue, we used mouse brown adipocytes in culture. Proliferating brown
      adipocytes had high levels of glucose transporter (GLUT) 1 mRNA and low levels of
      GLUT4 mRNA. The ratio of GLUT4/GLUT1 mRNA expression increased during
      differentiation, and mature brown adipocytes had high levels of GLUT4 mRNA. The
      endogenous adrenergic neurotransmitter norepinephrine induced a potent increase
      in GLUT1 mRNA and a decrease of GLUT4 mRNA in mature brown adipocytes. The
      norepinephrine effect was mimicked by isoprenaline and CL 316243 and was thus
      mediated by beta3-adrenergic receptors. The cAMP analog 8-bromoadenosine-cAMP
      partly mimicked the response on GLUT1 mRNA increase and fully mimicked the GLUT4
      mRNA decrease. We found no involvement of alpha1 or alpha2-adrenergic receptors
      on GLUT1 or GLUT4 mRNA transcription. Norepinephrine treatment led to a large
      increase of GLUT1 protein amount in brown adipocytes as visualized with
      immunocytochemical staining and subcellular fractionation. A large part of the
      newly synthesized GLUT1 was found in the plasma membrane (PM). The potent
      transcriptional inhibitor actinomycin D fully abolished this increase of GLUT1
      protein at all time points examined. Norepinephrine treatment shifted GLUT4 from
      the PM to an intracellular vesicular compartment. Norepinephrine increased 2
      deoxy-D-glucose uptake 2-fold at an early time point (1 h) and 4-fold at later
      time point (5 h). Addition of actinomycin D did not block the early phase but
      blocked a large part of the later phase of 2-deoxy-D-glucose uptake. These
      results imply that adrenergic stimulation through beta3-adrenergic receptors
      induces glucose uptake in brown adipocytes via two mechanisms: 1) a mechanism not
      dependent on GLUT1 and GLUT4 translocation, 2) a mechanism that is dependent on
      de novo synthesis of GLUT1 protein and increase of GLUT1 protein at the PM.

PMID- 16959849
TI  - Interleukin-1beta attenuates renin gene expression via a mitogen-activated
      protein kinase kinase-extracellular signal-regulated kinase and signal transducer
      and activator of transcription 3-dependent mechanism in As4.1 cells.
AB  - The precise mechanism by which cytokines such as IL-1beta negatively modulate
      expression of the renin gene remains incomplete. IL-1beta can repress renin
      transcription under both baseline and retinoic acid-stimulated conditions in
      As4.1 cells, a renin-expressing cell line derived from the kidney. This
      repression does not require a negative regulatory element present in the renin
      enhancer but is optimal in the presence of the entire renin enhancer. Three
      tandem copies of the retinoic acid response element is sufficient to attenuate
      the retinoic acid-response by IL-1beta. The decrease in retinoic acid-induced
      renin promoter activity in response to IL-1beta was blocked with the general
      tyrosine kinase inhibitor Genistein. IL-1beta caused an increase in the
      phosphorylation of ERK, but not p38MAPK or c-Jun N-terminal kinase. PD98059, an
      Erk kinase inhibitor, significantly decreased IL-1beta-mediated phosphorylation
      of ERK1/2, and attenuated the repression of baseline renin transcription in
      response to IL-1beta. PD98059 partially reversed the IL-1beta effect on retinoic
      acid-mediated transcription. To further investigate this mechanism, we searched
      the downstream effectors of ERK1/2 pathway. Although there was no effect of IL
      1beta on the phosphorylation of ELK, Janus kinase 2, or signal transducers and
      activators of transcription (STAT) 1, IL-1beta significantly increased tyrosine
      phosphorylation of STAT3, an effect attenuated by PD98059. STAT3 overexpression
      significantly repressed transcription of the renin gene, whereas small
      interfering RNA-mediated knockdown of STAT3 increased renin at baseline and
      attenuated the IL-1beta response. We conclude that in As4.1 cells, IL-1beta down
      regulates renin gene expression via a mechanism involving the Erk-STAT3 pathway.

PMID- 16959850
TI  - Direction selectivity in rabbit retina.

PMID- 16959851
TI  - Dynamic but not constitutive association of calmodulin with rat TRPV6 channels
      enables fine tuning of Ca2+-dependent inactivation.
AB  - The Ca(2+)-selective TRPV6 as well as the L-type Ca(2+) channel are regulated by
      the Ca(2+)-binding protein calmodulin (CaM). Here, we investigated the
      interaction of CaM with rat (r)TRPV6 in response to alterations of intracellular
      Ca(2+), employing Ca(2+)-imaging and patch-clamp techniques. Additionally,
      confocal Forster resonance energy transfer (FRET) microscopy on living cells was
      utilized as a key method to visualize in vivo protein-protein interactions
      essential for CaM regulation of rTRPV6 activity. The effects of overexpressed CaM
      or its Ca(2+)-insensitive mutant (CaM(MUT)) was probed on various rTRPV6 mutants
      and fragments in an attempt to elucidate the molecular mechanism of Ca(2+)/CaM
      dependent regulation and to pinpoint the physiologically relevant rTRPV6-CaM
      interaction site. A significant reduction of rTRPV6 activity, as well as an
      increase in current inactivation, were observed when CaM was overexpressed in
      addition to endogenous CaM. The Ca(2+)-insensitive CaM(MUT), however, failed to
      affect rTRPV6-derived currents. Accordingly, live cell confocal FRET microscopy
      revealed a robust interaction for CaM but not CaM(MUT) with rTRPV6, suggesting a
      strict Ca(2+) dependence for their association. Indeed, interaction of rTRPV6 or
      its C terminus with CaM increased with rising intracellular Ca(2+) levels, as
      observed by dynamic FRET measurements. An rTRPV6Delta(695-727) mutant with the
      very C-terminal end deleted, yielded Ca(2+) currents with a markedly reduced
      inactivation in accordance with a lack of CaM interaction as substantiated by
      FRET microscopy. These results, in contrast with those for CaM-dependent L-type
      Ca(2+) channel inactivation, demonstrate a dynamic association of CaM with the
      very C-terminal end of rTRPV6 (aa 695-727), and this enables acceleration of the
      rate of rTRPV6 current inactivation with increasing intracellular CaM
      concentrations.

PMID- 16959852
TI  - Targeted expression of Kir6.2 in mitochondria confers protection against hypoxic
      stress.
AB  - Selective K(+) transport in the inner mitochondrial membrane has been attributed
      to at least three different channel types: ATP-sensitive, Ca(2+)-regulated and
      voltage-dependent K(+) channels. Studies utilizing their selective modulators
      have suggested that an increased activity of these channels plays an important
      role in the cellular protection from metabolic stress. However, direct evidence
      for this effect is largely absent, and recent findings on the lack of specificity
      for several channel openers and blockers have questioned the actual contribution
      of the mitochondrial K(+) channels in the preservation of cellular viability. In
      order to directly investigate the role of enhanced mitochondrial K(+) uptake in
      cellular protection, we selectively expressed the inward rectifying K(+) channel
      Kir6.2 in the mitochondria of HEK293 and HL-1 cells. Targeted Kir6.2 expression
      was achieved by cloning the Kir6.2 gene in pCMV/mito/GFP vector and the proper
      trafficking to mitochondria was confirmed by colocalization studies and Western
      blot. An increased K(+) influx to mitochondria overexpressing Kir6.2, as
      evidenced by using the K(+)-sensitive PBFI AM fluorescent dye, substantially
      improved the cellular viability after hypoxic stress, which was assessed by
      lactate dehydrogenase (LDH) release. In parallel, monitoring of mitochondrial
      Ca(2+) during stress, via the specific indicator rhod-2, revealed a significant
      attenuation of Ca(2+) accumulation in mitochondria overexpressing K(+) channels.
      This effect was abolished in mitochondria expressing an inactive mutant of
      Kir6.2. Mitochondria expressing Kir6.2 K(+) channel also exhibited a significant
      degree of depolarization that became even more pronounced during the stress. In
      conclusion, this study provides the first non-pharmacological evidence that an
      increased K(+) influx to mitochondria protects against hypoxic stress by
      preventing detrimental effects of Ca(2+) overload.

PMID- 16959853
TI  - Specific modulation of motor unit discharge for a similar change in fascicle
      length during shortening and lengthening contractions in humans.
AB  - This study examines the effect of a change in fascicle length on motor unit
      recruitment and discharge rate in the human tibialis anterior during shortening
      and lengthening contractions that involved a similar change in torque. The
      dorsiflexor torque and the surface and intramuscular electromyograms (EMGs) from
      the tibialis anterior were recorded in eight subjects. The behaviour of the same
      motor unit (n=63) was compared during submaximal shortening and lengthening
      contractions performed at a constant velocity (10 deg s-1) with the dorsiflexor
      muscles over a 20 deg range of motion around the ankle neutral position. Muscle
      fascicle length was measured non-invasively using ultrasonography. Motor units
      that were active during a shortening contraction were always active during the
      subsequent lengthening contraction. Furthermore, additional motor units (n=18) of
      higher force threshold that were recruited during the shortening contraction to
      maintain the required torque were derecruited first during the following
      lengthening contraction. Although the change in fascicle length was linear
      (r2>0.99), and similar for both shortening and lengthening contractions,
      modulation of discharge rate differed during the two contractions. Compared with
      an initial isometric contraction at short (11.9+/-2.4 Hz) or long (11.7+/-2.2 Hz)
      muscle length, discharge rate increased only slightly and stayed nearly constant
      throughout the lengthening contraction (12.6+/-2.0 Hz; P<0.05) whereas it
      augmented progressively and more substantially during the shortening contraction,
      reaching 14.5+/-2.5 Hz (P<0.001) at the end of the movement. In conclusion, these
      observations indicate a clear difference in motor unit discharge rate modulation
      with no change in their recruitment order between shortening and lengthening
      contractions when performed with a similar change in muscle fascicle length and
      torque.

PMID- 16959854
TI  - Real-time measurement of serotonin release and motility in guinea pig ileum.
AB  - Enterochromaffin (EC) cells are sensors that detect chemical or mechanical
      stimuli and respond with release of serotonin (5-HT). 5-HT activates local motor
      reflexes, but whether local motor reflexes also evoke 5-HT release is unknown.
      The aim of the present study was to establish the relationship between the
      release of 5-HT and the enteric neural circuits controlling the movements of the
      intestine. Recordings were made from full-thickness preparations of guinea pig
      ileum using electrochemical techniques with carbon fibre electrodes to measure
      local concentrations of 5-HT. The tension in the circular muscle (CM) and
      longitudinal muscle (LM) was recorded with force transducers. The release of 5-HT
      from the EC cells was detected selectively and the timing of the events
      quantified. Pressure-evoked peristalsis caused detectable 5-HT release only when
      the recording site was invaded by a ring of CM contraction. Spontaneous and
      stretch-evoked reflex contraction of the CM and LM occurred simultaneously with 5
      HT release. Paralysis of the smooth muscle significantly reduced the stretch
      evoked release. Muscarinic agonists evoked reflexes that were associated with
      increases in tension in CM and LM simultaneous with 5-HT release. Tetrodotoxin
      abolished the coordination between the CM contraction and 5-HT release but not
      the direct activation of the CM and EC cells by the agonists. In conclusion, the
      correlation between local motor reflexes and 5-HT release observed in the present
      study is caused primarily by the contraction of the smooth muscle and subsequent
      deformation of the mucosa. The EC cell is, thus, a site of convergence for
      mechanical forces that contribute to the release of 5-HT during motor reflexes.

PMID- 16959855
TI  - Regional variations in the glial influence on synapse development in the mouse
      CNS.
AB  - There is increasing evidence that synapse function depends on interactions with
      glial cells, namely astrocytes. Studies on specific neurons of the central
      nervous system (CNS) indicated that glial signals also control synapse
      development, but it remained unclear whether this is a general principle that
      applies to other neuronal cell types. To address this question, we developed new
      methods to immunoisolate neurons from different brain regions of postnatal mice
      and to culture them in a chemically defined medium. Electrophysiological
      recordings and immunocytochemical staining revealed vigorous synaptogenesis in
      hippocampal and cerebellar neurons, but not in retinal ganglion cells (RGCs) in
      the absence of glial cells. Co-culture with glia promoted synapse formation in
      RGCs as indicated by a strong increase in the incidence and frequency of action
      potential-independent miniature synaptic currents, but showed no such effects in
      hippocampal or cerebellar neurons. On the other hand, glial signals promoted the
      efficacy of excitatory synapses in all regions as indicated by an increase in the
      size of spontaneous synaptic events in cerebellar cultures and of miniature
      synaptic currents in hippocampal neurons and RGCs. Inhibitory synaptic currents
      remained largely unaffected by glia. Our results indicate that in the mammalian
      CNS, the way that glial signals promote the development of excitatory synapses
      depends on the type of neuron.

PMID- 16959856
TI  - The ventral tegmental area revisited: is there an electrophysiological marker for
      dopaminergic neurons?
AB  - The ventral tegmental area (VTA) and in particular VTA dopamine (DA) neurons are
      postulated to play a central role in reward, motivation and drug addiction.
      However, most evidence implicating VTA DA neurons in these functions is based on
      indirect electrophysiological characterization, rather than cytochemical
      identification. These physiological criteria were first established in the
      substantia nigra pars compacta (SNc), but their validity in the VTA is uncertain.
      In the current study we found that while 88 +/- 2% of SNc neurons labelled by the
      neuronal marker NeuN were co-labelled for the catecholamine enzyme tyrosine
      hydroxylase (TH), a much smaller percentage (55 +/- 2%) of VTA neurons co
      expressed TH. In addition, using in vitro whole-cell recordings we found that
      widely accepted physiological criteria for VTA DA neurons, including the
      hyperpolarization-activated inwardly rectifying non-specific cation current
      (I(h)), spike duration, and inhibition by DA D2 receptor agonists, do not
      reliably predict the DA content of VTA neurons. We could not distinguish DA
      neurons from other VTA neurons by size, shape, input resistance, I(h) size, or
      spontaneous firing rate. Although the absence of an I(h) reliably predicted that
      a VTA neuron was non-dopaminergic, and I(h)(-) neurons differ from I(h)(+)
      neurons in firing rate, interspike interval (ISI) standard deviation, and ISI
      skew, no physiological property examined here is both sensitive and selective for
      DA neurons in the VTA. We conclude that reliable physiological criteria for VTA
      DA neuron identification have yet to be determined, and that the criteria
      currently being used are unreliable.

PMID- 16959857
TI  - Manually controlled human balancing using visual, vestibular and proprioceptive
      senses involves a common, low frequency neural process.
AB  - Ten subjects balanced their own body or a mechanically equivalent unstable
      inverted pendulum by hand, through a compliant spring linkage. Their balancing
      process was always characterized by repeated small reciprocating hand movements.
      These bias adjustments were an observable sign of intermittent alterations in
      neural output. On average, the adjustments occurred at intervals of approximately
      400 ms. To generate appropriate stabilizing bias adjustments, sensory information
      about body or load movement is needed. Subjects used visual, vestibular or
      proprioceptive sensation alone and in combination to perform the tasks. We first
      ask, is the time between adjustments (bias duration) sensory specific? Vision is
      associated with slow responses. Other senses involved with balance are known to
      be faster. Our second question is; does bias duration depend on sensory
      abundance? An appropriate bias adjustment cannot occur until unplanned motion is
      unambiguously perceived (a sensory threshold). The addition of more sensory data
      should therefore expedite action, decreasing the mean bias adjustment duration.
      Statistical analysis showed that (1) the mean bias adjustment duration was
      remarkably independent of the sensory modality and (2) the addition of one or two
      sensory modalities made a small, but significant, decrease in the mean bias
      adjustment duration. Thus, a threshold effect can alter only a very minor part of
      the bias duration. The bias adjustment duration in manual balancing must reflect
      something more than visual sensation and perceptual thresholds; our suggestion is
      that it is a common central motor planning process. We predict that similar
      processes may be identified in the control of standing.

PMID- 16959858
TI  - Development of respiratory control instability in heart failure: a novel approach
      to dissect the pathophysiological mechanisms.
AB  - Observational data suggest that periodic breathing is more common in subjects
      with low F(ETCO(2)), high apnoeic thresholds or high chemoreflex sensitivity. It
      is, however, difficult to determine the individual effect of each variable
      because they are intrinsically related. To distinguish the effect of isolated
      changes in chemoreflex sensitivity, mean F(ETCO(2)) and apnoeic threshold, we
      employed a modelling approach to break their obligatory in vivo
      interrelationship. We found that a change in mean CO(2) fraction from 0.035 to
      0.045 increased loop gain by 70 +/- 0.083% (P < 0.0001), irrespective of
      chemoreflex gain or apnoea threshold. A 100% increase in the chemoreflex gain
      (from 800 l min(-1) (fraction CO(2))(-1)) resulted in an increase in loop gain of
      275 +/- 6% (P < 0.0001) across a wide range of values of steady state CO(2) and
      apnoea thresholds. Increasing the apnoea threshold F(ETCO(2)) from 0.02 to 0.03
      had no effect on system stability. Therefore, of the three variables the only two
      destabilizing factors were high gain and high mean CO(2); the apnoea threshold
      did not independently influence system stability. Although our results support
      the idea that high chemoreflex gain destabilizes ventilatory control, there are
      two additional potentially controversial findings. First, it is high (rather than
      low) mean CO(2) that favours instability. Second, high apnoea threshold itself
      does not create instability. Clinically the apnoea threshold appears important
      only because of its associations with the true determinants of stability:
      chemoreflex gain and mean CO(2).

PMID- 16959859
TI  - Testosterone increases lactate transport, monocarboxylate transporter (MCT) 1 and
      MCT4 in rat skeletal muscle.
AB  - We have examined the effects of administration of testosterone for 7 days on
      monocarboxylate transporter (MCT) 1 and MCT4 mRNAs and proteins in seven
      metabolically heterogeneous rat hindlimb muscles and in the heart. In addition,
      we also examined the effects of testosterone treatment on plasmalemmal MCT1 and
      MCT4, and lactate transport into giant sarcolemmal vesicles prepared from red and
      white hindlimb muscles and the heart. Testosterone did not alter MCT1 or MCT4
      mRNA, except in the plantaris muscle. Testosterone increased MCT1 (20%-77%, P <
      0.05) and MCT4 protein (29%-110%, P< 0.05) in five out of seven muscles examined.
      In contrast, in the heart MCT1 protein was not increased (P> 0.05), and MCT 4
      mRNA and protein were not detected. There was no correlation between the
      testosterone-induced increments in MCT1 and MCT4 proteins. Muscle fibre
      composition was not associated with testosterone-induced increments in MCT1
      protein. In contrast, there was a strong positive relationship between the
      testosterone-induced increments in MCT4 protein and the fast-twitch fibre
      composition of rat muscles. Lactate transport into giant sarcolemmal vesicles was
      increased in red (23%, P< 0.05) and white muscles (21%, P< 0.05), and in the
      heart (58%, P< 0.05) of testosterone-treated animals (P< 0.05). However,
      plasmalemmal MCT1 protein (red, +40%, P< 0.05; white, +39%, P< 0.05) and
      plasmalemmal MCT4 protein (red, +25%, P< 0.05; white, +48%, P< 0.05) were
      increased only in skeletal muscle. In the heart, plasmalemmal MCT1 protein was
      reduced (-20%, P< 0.05). In conclusion, these studies have shown that
      testosterone induces an increase in both MCT1 and MCT4 proteins and their
      plasmalemmal content in skeletal muscle. However, the testosterone-induced effect
      was tissue-specific, as MCT1 protein expression was not altered in the heart. In
      the heart, the testosterone-induced increase in lactate transport cannot be
      explained by changes in plasmalemmal MCT1 content, but in skeletal muscle the
      increase in the rate of lactate transport was associated with increases in
      plasmalemmal MCT1 and MCT4.

PMID- 16959861
TI  - The dorsomedial hypothalamus: a new player in thermoregulation.
AB  - Neurons in the dorsomedial hypothalamus (DMH) play key roles in physiological
      responses to exteroceptive ("emotional") stress in rats, including tachycardia.
      Tachycardia evoked from the DMH or seen in experimental stress in rats is blocked
      by microinjection of the GABA(A) receptor agonist muscimol into the rostral raphe
      pallidus (rRP), an important thermoregulatory site in the brain stem, where
      disinhibition elicits sympathetically mediated activation of brown adipose tissue
      (BAT) and cutaneous vasoconstriction in the tail. Disinhibition of neurons in the
      DMH also elevates core temperature in conscious rats and sympathetic activity to
      least significant difference interscapular BAT (IBAT) and IBAT temperature in
      anesthetized preparations. The latter effects are blocked by microinjection of
      muscimol into the rRP, while microinjection of muscimol into either the rRP or
      DMH suppresses increases in sympathetic nerve activity to IBAT, IBAT temperature,
      and core body temperature elicited either by microinjection of PGE(2) into the
      preoptic area (an experimental model for fever), or central administration of
      fentanyl. Neurons concentrated in the dorsal region of the DMH project directly
      to the rRP, a location corresponding to that of neurons trans-synaptically
      labeled from IBAT. Thus these neurons control nonshivering thermogenesis in rats,
      and their activation signals its recruitment in diverse experimental paradigms.
      Evidence also points to a role for neurons in the DMH in thermoregulatory
      cutaneous vasoconstriction, shivering, and endocrine adjustments. These
      directions provide intriguing avenues for future exploration that may expand our
      understanding of the DMH as an important hypothalamic site for the integration of
      autonomic, endocrine, and behavioral responses to diverse challenges.

PMID- 16959860
TI  - Contribution of morphology and membrane resistance to integration of fast
      synaptic signals in two thalamic cell types.
AB  - Thalamocortical cells (TCs) and interneurons (INs) in the lateral geniculate
      nucleus process visual information from the retina. The TCs have many short
      dendrites, whereas the INs have fewer and longer dendrites. Because of these
      morphological differences, it has been suggested that transmission of synaptic
      signals from dendritic synapses to soma is more efficient in TCs than in INs.
      However, a higher membrane resistance (R(m)) for the INs could, in theory,
      compensate for the attenuating effect of their long dendrites and allow distal
      synaptic inputs to significantly depolarize the soma. Compartmental models were
      made from biocytin filled TCs (n = 15) and INs (n = 3) and adjusted to fit the
      current- and voltage-clamp recordings from the individual cells. The confidence
      limits for the passive electrical parameters were explored by simulating the
      influence of noise, morphometric errors and non-uniform and active conductances.
      One of the useful findings was that R(m) was accurately estimated despite
      realistic levels of active conductance. Simulations to explore the somatic
      influence of dendritic synapses showed that a small (0.5 nS) excitatory synapse
      placed at different dendritic positions gave similar somatic potentials in the
      individual TCs, within the TC population and also between TCs and INs. A linear
      increase in the conductance of the synapse gave increases in somatic potentials
      that were more sublinear in INs than TCs. However, when the total synaptic
      conductance was increased by simultaneously activating many small, spatially
      distributed synapses, the INs converted the synaptic signals to soma potentials
      almost as efficiently as the TCs. Thus, INs can transfer fast synaptic signals to
      soma as efficiently as TCs except when the focal conductance is large.

PMID- 16959862
TI  - Effect of acute severe hypoxia on peripheral fatigue and endurance capacity in
      healthy humans.
AB  - We hypothesized that severe hypoxia limits exercise performance via decreased
      contractility of limb locomotor muscles. Nine male subjects [mean +/- SE maximum
      O(2) uptake (Vo(2 max)) = 56.5 +/- 2.7 ml x kg(-1) x min(-1)] cycled at > or =90%
      Vo(2 max) to exhaustion in normoxia [NORM-EXH; inspired O(2) fraction (Fi(O(2)))
      = 0.21, arterial O(2) saturation (Sp(O(2))) = 93 +/- 1%] and hypoxia (HYPOX-EXH;
      Fi(O(2)) = 0.13, Sp(O(2)) = 76 +/- 1%). The subjects also exercised in normoxia
      for a time equal to that achieved in hypoxia (NORM-CTRL; Sp(O(2)) = 96 +/- 1%).
      Quadriceps twitch force, in response to supramaximal single (nonpotentiated and
      potentiated 1 Hz) and paired magnetic stimuli of the femoral nerve (10-100 Hz),
      was assessed pre- and at 2.5, 35, and 70 min postexercise. Hypoxia exacerbated
      exercise-induced peripheral fatigue, as evidenced by a greater decrease in
      potentiated twitch force in HYPOX-EXH vs. NORM-CTRL (-39 +/- 4 vs. -24 +/- 3%, P
      < 0.01). Time to exhaustion was reduced by more than two-thirds in HYPOX-EXH vs.
      NORM-EXH (4.2 +/- 0.5 vs. 13.4 +/- 0.8 min, P < 0.01); however, peripheral
      fatigue was not different in HYPOX-EXH vs. NORM-EXH (-34 +/- 4 vs. -39 +/- 4%, P
      > 0.05). Blood lactate concentration and perceptions of limb discomfort were
      higher throughout HYPOX-EXH vs. NORM-CTRL but were not different at end-exercise
      in HYPOX-EXH vs. NORM-EXH. We conclude that severe hypoxia exacerbates peripheral
      fatigue of limb locomotor muscles and that this effect may contribute, in part,
      to the early termination of exercise.

PMID- 16959863
TI  - Ghrelin improves burn-induced delayed gastrointestinal transit in rats.
AB  - Delayed gastrointestinal transit is common in patients with severe burn. Ghrelin
      is a potent prokinetic peptide. We aimed at testing the effect of ghrelin on burn
      induced delayed gastrointestinal transit in rats. Gastric emptying (GE),
      intestinal transit (IT), and colonic transit (CT) studies were performed in male
      Sprague-Dawley rats. Rats were randomized into two main groups as follows: sham
      injury and ghrelin-treated burn injury with doses of 0, 2, 5, and 10 nmol/rat ip
      6 h after burn. Sham/burn injury was induced under anesthesia. Rats received a
      phenol red meal 20 min following ghrelin injection. Based on the most effective
      ghrelin dose, 1 mg/kg sc atropine was given 30 min before the ghrelin in one
      group of rats for each study. The rats in each group were killed 30-90 min later;
      their stomachs, intestines, and colons were harvested immediately, and the amount
      of phenol red recovered was measured. Percentage of gastric emptying (GE%) and
      geometric center for IT and CT were calculated. We found 1) severe cutaneous burn
      injury significantly delayed GE, IT, and CT compared with sham injury (P < 0.05);
      2) ghrelin normalized both GE and IT, but not the CT; 3) the most effective dose
      of ghrelin was 2 nmol/rat; and 4) atropine blocked the prokinetic effects of
      ghrelin on GE% and IT. In conclusion, ghrelin normalizes burn-induced delayed GE
      and IT but has no effect on CT in rats. The prokinetic effects of ghrelin are
      exerted via the cholinergic pathway. Ghrelin may have a therapeutic potential for
      burn patients with delayed upper gastrointestinal transit.

PMID- 16959864
TI  - IGF-I and branchial IGF receptor expression and localization during salinity
      acclimation in striped bass.
AB  - The initial response of the IGF-I system and the expression and cellular
      localization of IGF type-I receptor (IGF-IR) were studied in the gill of a
      euryhaline teleost during salinity acclimation. Exposure of striped bass (Morone
      saxatilis) to hyperosmotic and hypoosmotic challenges induced small, transitory
      (<24 h) deflections in hydromineral balance. Transfer from freshwater (FW) to
      seawater (SW) induced an initial decrease in plasma IGF-I levels after 24 h in
      both fed and fasted fish. There was an overall decrease in liver IGF-I mRNA
      levels after SW transfer, suggesting that decreased plasma levels may be due to a
      decline in hepatic IGF-I synthesis. No changes were observed in gill IGF-I mRNA,
      but SW transfer induced an increase in gill IGF-IR mRNA after 24 h. Transfer from
      SW to FW induced an increase in plasma IGF-I levels in fasted fish. In fed fish,
      no significant changes were observed in either plasma IGF-I, liver, or gill IGF-I
      mRNA, or gill IGF-IR mRNA levels. In a separate experiment, FW-acclimated fish
      were injected with saline or IGF-I prior to a 24-h SW challenge. Rapid regain of
      osmotic balance following SW transfer was hindered by IGF-I. Immunohistochemistry
      revealed for the first time in teleosts that IGF-IR and Na(+)-K(+)-ATPase are
      localized in putative chloride cells at the base of the lamellae, identifying
      these cells in the gill as a target for IGF-I and IGF-II. Overall the data
      suggest a hyperosmoregulatory role of IGF-I in this species.

PMID- 16959865
TI  - Body temperature changes induced by huddling in breeding male emperor penguins.
AB  - Huddling is the key energy-saving mechanism for emperor penguins to endure their
      4-mo incubation fast during the Antarctic winter, but the underlying
      physiological mechanisms of this energy saving have remained elusive. The
      question is whether their deep body (core) temperature may drop in association
      with energy sparing, taking into account that successful egg incubation requires
      a temperature of about 36 degrees C and that ambient temperatures of up to 37.5
      degrees C may be reached within tight huddles. Using data loggers implanted into
      five unrestrained breeding males, we present here the first data on body
      temperature changes throughout the breeding cycle of emperor penguins, with
      particular emphasis on huddling bouts. During the pairing period, core
      temperature decreased progressively from 37.5 +/- 0.4 degrees C to 36.5 +/- 0.3
      degrees C, associated with a significant temperature drop of 0.5 +/- 0.3 degrees
      C during huddling. In case of egg loss, body temperature continued to decrease to
      35.5 +/- 0.4 degrees C, with a further 0.9 degrees C decrease during huddling. By
      contrast, a constant core temperature of 36.9 +/- 0.2 degrees C was maintained
      during successful incubation, even during huddling, suggesting a trade-off
      between the demands for successful egg incubation and energy saving. However,
      such a limited drop in body temperature cannot explain the observed energy
      savings of breeding emperor penguins. Furthermore, we never observed any signs of
      hyperthermia in huddling birds that were exposed to ambient temperatures as high
      as above 35 degrees C. We suggest that the energy savings of huddling birds is
      due to a metabolic depression, the extent of which depends on a reduction of body
      surface areas exposed to cold.

PMID- 16959866
TI  - Neuronal CCK and thermoregulation: two receptors with different functions.

PMID- 16959867
TI  - Modulation of membrane potential by an acetylcholine-activated potassium current
      in trout atrial myocytes.
AB  - Application of the current-clamp technique in rainbow trout atrial myocytes has
      yielded resting membrane potentials that are incompatible with normal atrial
      function. To investigate this paradox, we recorded the whole membrane current
      (I(m)) and compared membrane potentials recorded in isolated cardiac myocytes and
      multicellular preparations. Atrial tissue and ventricular myocytes had stable
      resting potentials of -87 +/- 2 mV and -83.9 +/- 0.4 mV, respectively. In
      contrast, 50 out of 59 atrial myocytes had unstable depolarized membrane
      potentials that were sensitive to the holding current. We hypothesized that this
      is at least partly due to a small slope conductance of I(m) around the resting
      membrane potential in atrial myocytes. In accordance with this hypothesis, the
      slope conductance of I(m) was about sevenfold smaller in atrial than in
      ventricular myocytes. Interestingly, ACh increased I(m) at -120 mV from 4.3 pA/pF
      to 27 pA/pF with an EC(50) of 45 nM in atrial myocytes. Moreover, 3 nM ACh
      increased the slope conductance of I(m) fourfold, shifted its reversal potential
      from -78 +/- 3 to -84 +/- 3 mV, and stabilized the resting membrane potential at 
      92 +/- 4 mV. ACh also shortened the action potential in both atrial myocytes and
      tissue, and this effect was antagonized by atropine. When applied alone, atropine
      prolonged the action potential in atrial tissue but had no effect on membrane
      potential, action potential, or I(m) in isolated atrial myocytes. This suggests
      that ACh-mediated activation of an inwardly rectifying K(+) current can modulate
      the membrane potential in the trout atrial myocytes and stabilize the resting
      membrane potential.

PMID- 16959869
TI  - Novel IgCAM, MDGA1, expressed in unique cortical area- and layer-specific
      patterns and transiently by distinct forebrain populations of Cajal-Retzius
      neurons.
AB  - The laminar and area patterning of the mammalian neocortex are two organizing
      principles that define its functional architecture. Members of the immunoglobulin
      (Ig) superfamily of cell adhesion molecules influence neural development by
      regulating cell adhesion, migration, and process growth. Here we describe the
      dynamic expression of the unique Ig-containing cell adhesion molecule, MAM domain
      containing glycosylphosphatidylinositol anchor 1 (MDGA1), during forebrain
      development in mice and compare it with other markers. We show that MDGA1 is a
      layer-specific marker and an area-specific marker, being expressed in layers 2/3
      throughout the neocortex, but within the primary somatosensory area (S1), MDGA1
      is also uniquely expressed in layers 4 and 6a. Comparisons with other markers,
      including cadherins, serotonin, cytochrome oxidase, ROR beta, and COUP-TF1,
      reveal unique features of patterned expression of MDGA1 within cortex and S1
      barrels. Further, our findings indicate that at earlier stages of development,
      MDGA1 is expressed by Reelin- and Tbr1-positive Cajal-Retzius neurons that
      originate from multiple sources outside of neocortex and emigrate into it. At
      even earlier stages, MDGA1 is expressed by the earliest diencephalic and
      mesencephalic neurons, which appear to migrate from a MDGA1-positive domain of
      progenitors in the diencephalon and form a "preplate." These findings show that
      MDGA1 is a unique marker for studies of cortical lamination and area patterning
      and together with recent reports suggest that MDGA1 has critical functions in
      forebrain/midbrain development.

PMID- 16959868
TI  - Neural basis for priming of pop-out during visual search revealed with fMRI.
AB  - Maljkovic and Nakayama first showed that visual search efficiency can be
      influenced by priming effects. Even "pop-out" targets (defined by unique color)
      are judged quicker if they appear at the same location and/or in the same color
      as on the preceding trial, in an unpredictable sequence. Here, we studied the
      potential neural correlates of such priming in human visual search using
      functional magnetic resonance imaging (fMRI). We found that repeating either the
      location or the color of a singleton target led to repetition suppression of
      blood oxygen level-dependent (BOLD) activity in brain regions traditionally
      linked with attentional control, including bilateral intraparietal sulci. This
      indicates that the attention system of the human brain can be "primed," in
      apparent analogy to repetition-suppression effects on activity in other neural
      systems. For repetition of target color but not location, we also found
      repetition suppression in inferior temporal areas that may be associated with
      color processing, whereas repetition of target location led to greater reduction
      of activation in contralateral inferior parietal and frontal areas, relative to
      color repetition. The frontal eye fields were also implicated, notably when both
      target properties (color and location) were repeated together, which also led to
      further BOLD decreases in anterior fusiform cortex not seen when either property
      was repeated alone. These findings reveal the neural correlates for priming of
      pop-out search, including commonalities, differences, and interactions between
      location and color repetition. fMRI repetition-suppression effects may arise in
      components of the attention network because these settle into a stable "attractor
      state" more readily when the same target property is repeated than when a
      different attentional state is required.

PMID- 16959870
TI  - Can deleterious mutations explain the time dependency of molecular rate
      estimates?
AB  - It has recently been observed by Ho et al. (Ho SYW, Phillips MJ, Cooper A,
      Drummond AJ. 2005. Time dependency of molecular rate estimates and systematic
      overestimation of recent divergence times. Mol Biol Evol. 22(7):1561-1568) that
      apparent rates of molecular evolution increase when measured over short
      timespans. I investigate whether the data are explainable purely by deleterious
      mutations. I derive an empirical approximation for the persistence of these
      mutations in a randomly mating population and, hence, derive lower limits on
      effective population sizes. These limits are high and get higher if additional
      reasonable assumptions are made. This casts doubt on whether deleterious
      mutations are able to explain the apparent rate acceleration.

PMID- 16959871
TI  - Identification of signaling molecules mediating corticotropin-releasing hormone
      R1alpha-mitogen-activated protein kinase (MAPK) interactions: the critical role
      of phosphatidylinositol 3-kinase in regulating ERK1/2 but not p38 MAPK
      activation.
AB  - In most target cells, activation of the type 1 CRH receptor (CRH-R1) by CRH or
      urocortin (UCN I) leads to stimulation of the Gs-protein/adenylyl cyclase/protein
      kinase A cascade. Signal transduction of CRH-R1 also involves alternative
      pathways such as phosphorylation of ERK1/2 and p38 MAPK, two members of the MAPK
      family that mediate important pathophysiological responses. The intracellular
      pathways by which CRH-R1 activates these MAPK are only partially understood; here
      we characterized further signaling mechanisms and molecules involved in CRH-R1
      mediated ERK1/2 and p38 MAPK activation. In human embryonic kidney 293 cells
      overexpressing recombinant CRH-R1alpha, UCN I induced ERK1/2 and p38 MAPK
      activation was dependent on signaling molecules involved in agonist-induced CRH
      R1alpha trafficking and endocytosis. Furthermore, time course studies and use of
      selective inhibitors demonstrated that ERK1/2 activation occured within 5 min,
      was sustained for at least 60 min, and was dependent on both phosphatidylinositol
      3-kinase (PI3-K)/Akt activation and epidermoid growth factor receptor
      transactivation involving matrix metelloproteinases. UCN I effect on p38 MAPK
      phosphorylation was more transient, returned to basal within 40 min and was
      dependent on epidermoid growth factor receptor transactivation, but not PI3-K/Akt
      activation. Overexpression of G(alpha-)transducin, showed that G(betagamma)
      subunit activation is only partially required for ERK1/2 phosphorylation and does
      not play a role in p38 MAPK phosphorylation, whereas overexpression of a dominant
      negative Ras (Ras N17) attenuated both ERK and p38 MAPK activation. In
      conclusion, a complex signaling network appears to mediate CRH-R1alpha-MAPK
      interactions; PI3-K might play a critical role in the regulation of CRH-R1alpha
      signaling selectivity and cellular responses.

PMID- 16959872
TI  - A growth hormone-releasing peptide that binds scavenger receptor CD36 and ghrelin
      receptor up-regulates sterol transporters and cholesterol efflux in macrophages
      through a peroxisome proliferator-activated receptor gamma-dependent pathway.
AB  - Macrophages play a central role in the pathogenesis of atherosclerosis by
      accumulating cholesterol through increased uptake of oxidized low-density
      lipoproteins by scavenger receptor CD36, leading to foam cell formation. Here we
      demonstrate the ability of hexarelin, a GH-releasing peptide, to enhance the
      expression of ATP-binding cassette A1 and G1 transporters and cholesterol efflux
      in macrophages. These effects were associated with a transcriptional activation
      of nuclear receptor peroxisome proliferator-activated receptor (PPAR)gamma in
      response to binding of hexarelin to CD36 and GH secretagogue-receptor 1a, the
      receptor for ghrelin. The hormone binding domain was not required to mediate
      PPARgamma activation by hexarelin, and phosphorylation of PPARgamma was increased
      in THP-1 macrophages treated with hexarelin, suggesting that the response to
      hexarelin may involve PPARgamma activation function-1 activity. However, the
      activation of PPARgamma by hexarelin did not lead to an increase in CD36
      expression, as opposed to liver X receptor (LXR)alpha, suggesting a differential
      regulation of PPARgamma-targeted genes in response to hexarelin. Chromatin
      immunoprecipitation assays showed that, in contrast to a PPARgamma agonist, the
      occupancy of the CD36 promoter by PPARgamma was not increased in THP-1
      macrophages treated with hexarelin, whereas the LXRalpha promoter was strongly
      occupied by PPARgamma in the same conditions. Treatment of apolipoprotein E-null
      mice maintained on a lipid-rich diet with hexarelin resulted in a significant
      reduction in atherosclerotic lesions, concomitant with an enhanced expression of
      PPARgamma and LXRalpha target genes in peritoneal macrophages. The response was
      strongly impaired in PPARgamma(+/-) macrophages, indicating that PPARgamma was
      required to mediate the effect of hexarelin. These findings provide a novel
      mechanism by which the beneficial regulation of PPARgamma and cholesterol
      metabolism in macrophages could be regulated by CD36 and ghrelin receptor
      downstream effects.

PMID- 16959873
TI  - Human homologs of the putative G protein-coupled membrane progestin receptors
      (mPRalpha, beta, and gamma) localize to the endoplasmic reticulum and are not
      activated by progesterone.
AB  - The steroid hormone progesterone exerts pleiotrophic functions in many cell
      types. Although progesterone controls transcriptional activation through binding
      to its nuclear receptors, it also initiates rapid nongenomic signaling events.
      Recently, three putative membrane progestin receptors (mPRalpha, beta, and gamma)
      with structural similarity to G protein-coupled receptors have been identified.
      These mPR isoforms are expressed in a tissue-specific manner and belong to the
      larger, highly conserved family of progestin and adiponectin receptors found in
      plants, eubacteria, and eukaryotes. The fish mPRalpha has been reported to
      mediate progesterone-dependent MAPK activation and inhibition of cAMP production
      through coupling to an inhibitory G protein. To functionally characterize the
      human homologs, we established human embryonic kidney 293 and MDA-MB-231 cell
      lines that stably express human mPRalpha, beta, or gamma. For comparison, we also
      established cell lines expressing the mPRalpha cloned from the spotted seatrout
      (Cynoscion nebulosus) and Japanese pufferfish (Takifugu rubripes). Surprisingly,
      we found no evidence that human or fish mPRs regulate cAMP production or MAPK
      (ERK1/2 or p38) activation upon progesterone stimulation. Furthermore, the mPRs
      did not couple to a highly promiscuous G protein subunit, Galpha(q5i), in
      transfection studies or provoke Ca(2+) mobilization in response to progesterone.
      Finally, we demonstrate that transfected mPRs, as well as endogenous human
      mPRalpha, localize to the endoplasmic reticulum, and that their expression does
      not lead to increased progestin binding either in membrane preparations or in
      intact cells. Our results therefore do not support the concept that mPRs are
      plasma membrane receptors involved in transducing nongenomic progesterone
      actions.

PMID- 16959874
TI  - A new mechanism for prolactin processing into 16K PRL by secreted cathepsin D.
AB  - Cathepsins are lysosomal enzymes that were shown to release the antiangiogenic
      fragments 16K prolactin (PRL), endostatin, and angiostatin by processing
      precursors at acidic pH in vitro. However, the physiological relevance of these
      findings is questionable because the neutral pH of physiological fluids is not
      compatible with the acidic conditions required for the proteolytic activity of
      these enzymes. Here we show that cathepsin D secreted from various tissues is
      able to process PRL into 16K PRL outside the cell. To specifically target
      extracellular proteolysis, we used tissues from PRL receptor-deficient mice,
      which are unable to internalize PRL. As assessed by the use of specific
      inhibitors of proton extruders, we show that the proteolytic activity of
      cathepsin D requires local acid secretion driven by Na(+)/H(+) exchangers and
      H(+)/ATPase. Although it is usually assumed that cathepsin-mediated generation of
      antiangiogenic peptides occurs in the moderately acidic pericellular milieu found
      in malignant tumors, we propose a new mechanism explaining the extracellular
      activity of this acidic protease under physiological pH. Our data support the
      concept that secreted lysosomal enzymes could be involved in the maintenance of
      angiogenesis dormancy via the generation of active antiangiogenic peptides in
      nonpathological contexts.

PMID- 16959875
TI  - The role of interleukin-11 in pregnancy involves up-regulation of alpha2
      macroglobulin gene through janus kinase 2-signal transducer and activator of
      transcription 3 pathway in the decidua.
AB  - IL-11 expressed by endometrial stromal cells is crucial for normal pregnancy. IL
      11 receptor alpha (IL-11Ralpha) null mice are infertile due to abnormal
      development of the placenta. In these mice, the mesometrial decidual tissue,
      which is the site of trophoblast invasion, thins and disappears at mid-pregnancy.
      Degeneration of the decidua is accompanied by uncontrolled trophoblast invasion.
      In this report, we show, using IL-11Ralpha null mice, that a defect in IL-11
      signaling in the decidua leads to severe down-regulation of alpha(2)
      macroglobulin (alpha(2)-MG), a metalloproteinase inhibitor crucial for limiting
      trophoblast invasion. We also present evidence, using uterine stromal cells that
      decidualize in culture, that IL-11 robustly stimulates the endogenous alpha(2)-MG
      expression and enhances alpha(2)-MG promoter activity. Serial 5' deletion and
      internal deletion of the promoter reveal two important signal transducer and
      activator of transcription (Stat) binding sites. Mutation of either one of these
      motifs decreases IL-11 stimulation, whereas double mutation prevents IL-11
      action. We also found that IL-11 activates Janus kinase 2 (Jak2) and induces
      rapid phosphorylation, nuclear translocation, and promoter binding activity of
      Stat3 in decidual cells, whereas Jak1, Tyk2, and Stat5 activities are not
      affected. In addition, Jak2 inhibitor totally prevents alpha(2)-MG expression in
      decidual cells. Taken together, results of this investigation provide, at least
      in part, an explanation for the overinvasiveness of the trophoblast in IL
      11Ralpha null mice and reveal, for the first time, that IL-11 signals through the
      Jak2/Stat3 pathway in decidual cells to stimulate the expression of alpha(2)-MG,
      a protease inhibitor essential for normal placentation in pregnancy.

PMID- 16959876
TI  - The notch signaling system is present in the postnatal pituitary: marked
      expression and regulatory activity in the newly discovered side population.
AB  - Recently, we discovered in the adult anterior pituitary a subset of cells with
      side population (SP) phenotype, enriched for expression of stem/progenitor cell
      associated factors like Sca1, and of Notch1 and Hes (hairy and enhancer of split)
      1, components of the classically developmental Notch pathway. In the present
      study, we elaborated the expression of the Notch signaling system in the
      postnatal pituitary, and examined its functional significance within the SP
      compartment. Using RT-PCR, we detected in the anterior pituitary of adult mouse
      the expression of all four vertebrate Notch receptors, as well as of Hes1, 5, and
      6, key downstream targets and effectors of Notch. All Notch receptors, Hes1 and
      Hes5 were measured at higher mRNA levels in the Sca1(high) SP than in the main
      population (MP) of differentiated hormonal cells. In contrast, Hes6, known as an
      inhibitor of Hes1, was more abundant in the MP. Cells with SP phenotype, enriched
      for Sca1(high) expression, were detected throughout postnatal life. Their
      proportion was higher in immature mice, but did not change from adult (8 wk old)
      to much older age (1 yr old). Notch pathway expression was higher in the
      Sca1(high) SP than in the MP at all postnatal ages analyzed. Functional
      implication of Notch signaling in the SP was investigated in reaggregate cultures
      of adult mouse anterior pituitary cells. Treatment with the gamma-secretase
      inhibitor DAPT down-regulated Notch activity and reduced the proportion of SP
      cells. Activation of Notch signaling with the conserved DSL motif of Notch
      ligands, or with a soluble ligand, caused a rise in SP cell number, at least in
      part due to a proliferative effect. The SP also expanded in proportion when
      aggregates were treated with leukemia-inhibitory factor, basic fibroblast growth
      factor, and epidermal growth factor, again at least partly accounted for by a
      mitogenic action. These intrapituitary growth factors all activated Notch
      signaling, and DAPT abrogated the expansion of the SP by basic fibroblast growth
      factor and leukemia-inhibitory factor, thus exposing a possible cross talk. In
      conclusion, we show that the Notch pathway, typically situated in embryogenesis,
      is also present and active in the postnatal pituitary, that it is particularly
      expressed within the SP independent of age, and that it plays a role in the
      regulation of SP abundance. Whether our data indicate that Notch regulates
      renewal and fate decisions of putative stem/progenitor cells within the pituitary
      SP as found in other tissues, remains open for further exploration.

PMID- 16959877
TI  - Mechanisms for growth factor-induced pituitary tumor transforming gene-1
      expression in pituitary folliculostellate TtT/GF cells.
AB  - PTTG1, a securin protein, also behaves as a transforming gene and is
      overexpressed in pituitary tumors. Because pituitary folliculostellate (FS) cells
      regulate pituitary tumor growth factors by paracrine mechanisms, epidermal growth
      factor (EGF) receptor (EGFR)-mediated PTTG1 expression and cell proliferation was
      tested in pituitary FS TtT/GF cells. EGFR ligands caused up to 3-fold induction
      of Pttg1 mRNA expression, enhanced proliferating cell nuclear antigen, and
      increased entry of G0/1-arrested cells into S-phase. PTTG binding factor mRNA
      expression was not altered. EGF-induced Pttg1 expression and cell proliferation
      was abolished by preincubation of TtT/GF cells with EGFR inhibitors AG1478 and
      gefitinib. Phosphatidylinositol 3 kinase, protein kinase C, and MAPK, but not c
      Jun N-terminal kinase and Janus activating kinase signaling regulated EGF-induced
      Pttg1, as well as proliferating cell nuclear antigen mRNA expression and entry
      into S-phase. EGF-induced EGFR and ERK1/2 phosphorylation was followed by rapid
      MAPK kinase/ERK kinase-dependent activation of Elk-1 and c-Fos. EGF-induced Pttg1
      expression peaked at the S-G2 transition and declined thereafter. Pttg1 cell
      cycle dependency was confirmed by suppression of EGF-induced Pttg1 mRNA by
      blockade of cells in early S-phase. The results show that PTTG1 and its binding
      protein PTTG binding factor are expressed in pituitary FS TtT/GF cells. EGFR
      ligands induce PTTG1 and regulate S-phase, mediated by phosphatidylinositol 3
      kinase, protein kinase C, and MAPK pathways. PTTG1 is therefore a target for EGFR
      mediated paracrine regulation of pituitary cell growth.

PMID- 16959878
TI  - The role of P-glycoprotein in the bioactivation of raloxifene.
AB  - Drug transporters have been shown to alter drug metabolism. Similarly,
      bioactivation of drugs may also be altered by drug transporters. The aim of this
      work was to examine the role of P-glycoprotein (Pgp) in the bioactivation of a
      Pgp substrate, raloxifene, and a non-Pgp substrate, naphthalene. To evaluate the
      extent of bioactivation, covalent binding was measured. In both freshly isolated
      and cryopreserved hepatocytes, the extent of raloxifene covalent binding
      increased significantly (p < 0.05) in the presence of verapamil, whereas no
      change was observed with the covalent binding of naphthalene. To ascertain that
      the change was a Pgp effect, covalent binding was examined in microsomes in which
      raloxifene and naphthalene covalent binding was not altered in the presence of
      verapamil. In addition, the measure of raloxifene-glutathione adducts in the
      cryopreserved hepatocytes showed that the formation of the adducts increased in
      the presence of verapamil, which supports the idea that blocking Pgp in the liver
      increases metabolism and, therefore, the bioactivation of raloxifene. Because
      raloxifene and naphthalene are known to undergo bioactivation mediated by CYP3A4,
      covalent binding in the presence of ketoconazole was examined. In both
      hepatocytes and microsomes, raloxifene covalent binding decreased significantly
      (p < 0.01). It is interesting that naphthalene covalent binding was not affected.
      In the presence of the CYP2E inhibitor 4-methylpyrazole, a decrease in
      naphthalene covalent binding was observed, suggesting that the formation of the
      1,2-epoxide may be the main culprit contributing to naphthalene covalent binding.
      In conclusion, these data suggest that in addition to other "protective"
      mechanisms, Pgp may attenuate bioactivation of drugs.

PMID- 16959879
TI  - Comparative metabolism and disposition of trichloroethylene in Cyp2e1-/-and wild
      type mice.
AB  - Trichloroethylene (TCE)1 is an important environmental contaminant, a well
      established rodent carcinogen, and a "probable human carcinogen". Metabolism of
      TCE occurs primarily via cytochrome P450 (P450)-dependent oxidation. In vitro
      studies suggested that CYP2E1 is the principal high-affinity enzyme responsible
      for TCE metabolism. The objective of the present work is to more directly assess
      the role of CYP2E1 in the metabolism and disposition of 1,2-14C-TCE administered
      at 250 or 1000 mg/kg (gavage) using Cyp2e1-/-[knockout (KO)] versus wild-type
      (WT) mice. After dosing, animals were individually placed in glass metabolism
      cages that allowed the collection of expired air, urine, and feces. Exhalation of
      TCE-derived 14CO2 increased in a dose-dependent manner in mice of both genotypes
      and was significantly higher in WT versus KO mice. A significantly greater
      percentage of the dose was exhaled in KO versus WT mice as organic volatiles
      (mainly as TCE). Urinary excretion was the major route of TCE metabolism in WT
      mice, and the percentage of dose eliminated in urine was significantly higher at
      the 250 versus 1000 mg/kg dose. Furthermore, urinary excretion and CO2 exhalation
      significantly decreased in KO versus WT mice. Pretreatment with 1
      aminobenzotriazole clearly inhibited TCE metabolism as evident from increased
      exhalation of parent TCE, and decreased urinary excretion and CO2 exhalation in
      mice of both genotypes. In conclusion, these data showed that whereas CYP2E1
      plays an important role in TCE metabolism and disposition, other P450s also play
      a significant role and may explain earlier results showing that TCE causes lung
      damage in KO and WT mice.

PMID- 16959880
TI  - A bio-chemo-mechanical model for cell contractility.
AB  - A general model for the contractility of cells is presented that accounts for the
      dynamic reorganization of the cytoskeleton. The model is motivated by three key
      biochemical processes: (i) an activation signal that triggers actin
      polymerization and myosin phosphorylation, (ii) the tension-dependent assembly of
      the actin and myosin into stress fibers, and (iii) the cross-bridge cycling
      between the actin and myosin filaments that generates the tension. Simple
      relations are proposed to model these coupled phenomena and a continuum model
      developed for simulating cell contractility. The model is capable of predicting
      key experimentally established characteristics including: (i) the decrease in the
      forces generated by the cell with increasing substrate compliance, (ii) the
      influence of cell shape and boundary conditions on the development of structural
      anisotropy, and (iii) the high concentration of the stress fibers at the focal
      adhesions. We present numerical examples of a square cell on four supports to
      demonstrate these capabilities.

PMID- 16959881
TI  - Human cytomegalovirus infection alters the substrate specificities and rapamycin
      sensitivities of raptor- and rictor-containing complexes.
AB  - Signaling mediated by the mammalian target of rapamycin kinase (mTOR) is
      activated during human cytomegalovirus (HCMV) infection. mTOR is found in two
      complexes differing by the binding partner, rictor or raptor. Activated mTOR
      raptor promotes cap-dependent translation through the hyperphosphorylation of the
      eIF4E-binding protein (4E-BP). This activity of the raptor complex is normally
      inhibited by cell stress responses or the drug rapamycin. However, we previously
      showed that this inhibition of mTOR signaling can be circumvented during HCMV
      infection such that hyperphosphorylation of 4E-BP is maintained. Here we show
      that HCMV infection also activates the rictor complex, as indicated by increased
      phosphorylation of Akt S473; this phosphorylation is insensitive to rapamycin but
      sensitive to caffeine in both uninfected and infected cells. By using short
      hairpin RNAs to deplete rictor and raptor, we find that rictor is more
      significant than raptor for the viral infection. Surprisingly, the inhibitory
      effects of rapamycin on viral growth are primarily due to the presence of rictor,
      not raptor. Raptor and rictor depletion experiments show that in HCMV-infected
      cells, both raptor- and rictor-containing complexes can mediate the
      hyperphosphorylation of 4E-BP and the phosphorylation of p70S6 kinase. Under
      these conditions, the rictor complex is rapamycin-sensitive for the
      hyperphosphorylation of 4E-BP, but the raptor complex is not. These data suggest
      that, during HCMV infection, the rictor- and raptor-containing complexes are
      modified such that their substrate specificities and rapamycin sensitivities are
      altered. Our data also suggest that the present understanding of rapamycin's
      inhibitory effects is incomplete.

PMID- 16959882
TI  - Loss of Apc allows phenotypic manifestation of the transforming properties of an
      endogenous K-ras oncogene in vivo.
AB  - Oncogenic mutations in the K-ras gene occur in approximately 50% of human
      colorectal cancers. However, the precise role that K-ras oncogenes play in tumor
      formation is still unclear. To address this issue, we have conditionally
      expressed an oncogenic K-ras(V12) allele in the small intestine of adult mice
      either alone or in the context of Apc deficiency. We found that expression of K
      ras(V12) does not affect normal intestinal homeostasis or the immediate
      phenotypes associated with Apc deficiency. Mechanistically we failed to find
      activation of the Raf/MEK/ERK pathway, which may be a consequence of the up
      regulation of a number of negative feedback loops. However, K-ras(V12) expression
      accelerates intestinal tumorigenesis and confers invasive properties after Apc
      loss over the long term. In renal epithelium, expression of the oncogenic K
      ras(V12) allele in the absence of Apc induces the rapid development of renal
      carcinoma. These tumors, unlike those of intestinal origin, display activation of
      the Raf/MEK/ERK and Akt signaling pathways. Taken together, these data indicate
      that normal intestinal and kidney epithelium are resistant to malignant
      transformation by an endogenous K-ras oncogene. However, activation of K-ras(V12)
      after Apc loss results in increased tumorigenesis with distinct kinetics. Whereas
      the effect of K-ras oncogenes in the intestine can been observed only after long
      latencies, they result in rapid carcinogenesis in the kidney epithelium. These
      data imply a window of opportunity for anti-K-ras therapies after tumor
      initiation in preventing tumor growth and invasion.

PMID- 16959883
TI  - The p47 GTPases Igtp and Irgb10 map to the Chlamydia trachomatis susceptibility
      locus Ctrq-3 and mediate cellular resistance in mice.
AB  - Infections caused by the bacteria Chlamydia trachomatis contribute to diverse
      pathologies in a variety of human populations. We previously used a systemic
      model of C. trachomatis infection in mice to map three quantitative trait loci
      that influence in vivo susceptibility differences between the C57BL/6J and
      C3H/HeJ inbred strains of mouse. One of these quantitative trait loci, Ctrq-3,
      influences an IFN-gamma-dependent susceptibility difference in primary embryonic
      fibroblasts isolated from these strains. Here we use fine structure mapping in
      congenic fibroblasts carrying DNA from the susceptible parent to localize the
      effect of Ctrq-3 to a 1.2-megabase interval of genomic DNA that contains Irgb10
      and Igtp, two members of the IFN-gamma-inducible p47 family of GTPases. This
      class of proteins has been widely implicated in resistance to intracellular
      pathogens in mice. We analyzed expression of Irgb10 and Igtp in parental and
      congenic embryonic fibroblasts treated with IFN-gamma and found that relatively
      resistant fibroblasts express more Irgb10 than relatively susceptible
      fibroblasts. However, we also found that abolishing the expression of either
      Irgb10 or Igtp increases susceptibility of embryonic fibroblasts to C.
      trachomatis. Thus, we conclude that, although a difference in Irgb10 expression
      is likely responsible for the effect of Ctrq-3 on susceptibility to C.
      trachomatis, both genes play a role in intracellular resistance to C.
      trachomatis.

PMID- 16959884
TI  - Progestin negatively affects hearing in aged women.
AB  - Female hormone influences on auditory system aging are not completely understood.
      Because of widespread clinical use of hormone replacement therapy (HRT), it is
      critical to understand HRT effects on sensory systems. The present study
      retrospectively analyzed and compared hearing abilities among 124 postmenopausal
      women taking HRT, treated with estrogen and progestin (E+P; n = 32), estrogen
      alone (E; n = 30), and a third [non-hormone replacement therapy (NHRT; n = 62)]
      control group. Subjects were 60-86 years old and were matched for age and health
      status. All had relatively healthy medical histories and no significant noise
      exposure, middle-ear problems, or major surgeries. Hearing tests included pure
      tone audiometry, tympanometry, distortion-product otoacoustic emissions (DPOAEs),
      transient otoacoustic emissions, and the hearing-in-noise test (HINT). The HINT
      tests for speech perception in background noise, the major complaint of hearing
      impaired persons. Pure-tone thresholds in both ears were elevated (poorer) for
      the E+P relative to the E and control groups. For DPOAEs, the E+P group presented
      with lower (worse) levels than the E and control groups, with significant
      differences for both ears. For the HINT results, the E+P group had poorer speech
      perception than the E and control groups across all background noise speaker
      locations and in quiet. These findings suggest that the presence of P as a
      component of HRT results in poorer hearing abilities in aged women taking HRT,
      affecting both the peripheral (ear) and central (brain) auditory systems, and it
      interferes with the perception of speech in background noise.

PMID- 16959885
TI  - Identification of biomarkers that distinguish human papillomavirus (HPV)-positive
      versus HPV-negative head and neck cancers in a mouse model.
AB  - Head and neck squamous cell carcinoma (HNSCC) is a leading cause of cancer
      mortality worldwide. Recent reports have associated a subset of HNSCC with high
      risk human papillomaviruses (HPVs), particularly HPV16, the same subset of HPVs
      responsible for the majority of cervical and anogenital cancers. In this study we
      describe a mouse model for HPV-associated HNSCC that employs mice transgenic for
      the HPV16 oncogenes E6 and E7. In these mice, E6 and E7 induce aberrant
      epithelial proliferation and, in the presence of a chemical carcinogen, they
      increase dramatically the animal's susceptibility to HNSCC. The cancers arising
      in the HPV16-transgenic mice mirror the molecular and histopathological
      characteristics of human HPV-positive HNSCC that distinguish the latter from
      human HPV-negative HNSCC, including overexpression of p16 protein and formation
      of more basaloid cancers. This validated model of HPV-associated HNSCC provides
      the means to define the contributions of individual HPV oncogenes to HNSCC and to
      understand the molecular basis for the differing clinical properties of HPV
      positive and HPV-negative human HNSCC. From this study, we identify
      minichromosome maintenance protein 7 (MCM7) and p16 as potentially useful
      biomarkers for HPV-positive head and neck cancer.

PMID- 16959886
TI  - Disulfide isomerization switches tissue factor from coagulation to cell
      signaling.
AB  - Cell-surface tissue factor (TF) binds the serine protease factor VIIa to activate
      coagulation or, alternatively, to trigger signaling through the G protein
      coupled, protease-activated receptor 2 (PAR2) relevant to inflammation and
      angiogenesis. Here we demonstrate that TF.VIIa-mediated coagulation and cell
      signaling involve distinct cellular pools of TF. The surface-accessible,
      extracellular Cys186-Cys209 disulfide bond of TF is critical for coagulation, and
      protein disulfide isomerase (PDI) disables coagulation by targeting this
      disulfide. A TF mutant (TF C209A) with an unpaired Cys186 retains TF.VIIa
      signaling activity, and it has reduced affinity for VIIa, a characteristic of
      signaling TF on cells with constitutive TF expression. We further show that PDI
      suppresses TF coagulant activity in a nitric oxide-dependent pathway, linking the
      regulation of TF thrombogenicity to oxidative stress in the vasculature.
      Furthermore, a unique monoclonal antibody recognizes only the noncoagulant,
      cryptic conformation of TF. This antibody inhibits formation of the TF.PAR2
      complex and TF.VIIa signaling, but it does not prevent coagulation activation.
      These experiments delineate an upstream regulatory mechanism that controls TF
      function, and they provide initial evidence that TF.VIIa signaling can be
      specifically inhibited with minimal effects on coagulation.

PMID- 16959887
TI  - Evolution of protein structural classes and protein sequence families.
AB  - In protein structure space, protein structures cluster into four elongated
      regions when mapped based solely on similarity among the 3D structures. These
      four regions correspond to the four major classes of present-day proteins defined
      by the contents of secondary structure types and their topological arrangement.
      Evolution of and restriction to these four classes suggest that, in most cases,
      the evolution of genes may have been constrained or selected to those genetic
      changes that results in structurally stable proteins occupying one of the four
      "allowed" regions of the protein structure space, "structural selection," an
      important component of natural selection in gene evolution. Our studies on
      tracing the "common structural ancestor" for each protein sequence family of
      known structure suggest that: (i) recently emerged proteins belong mostly to
      three classes; (ii) the proteins that emerged earlier evolved to gain a new
      class; and (iii) the proteins that emerged earliest evolved to become the present
      day proteins in the four major classes, with the fourth-class proteins becoming
      the most dominant population. Furthermore, our studies also show that not all
      present-day proteins evolved from one single set of proteins in the last common
      ancestral organism, but new common ancestral proteins were "born" at different
      evolutionary times, not traceable to one or two ancestral proteins: "the multiple
      birth model" for the evolution of protein sequence families.

PMID- 16959889
TI  - Highly cross-linked polyethylene in total hip arthroplasty.
AB  - Although total hip arthroplasty is a common and highly successful procedure, its
      long-term durability has been undermined by the cellular response to polyethylene
      wear debris and the subsequent effects on periprosthetic bone. Research
      elucidating the effects of sterilization on polyethylene wear has facilitated the
      development of a more wear-resistant material-highly cross-linked polyethylene.
      Laboratory testing has demonstrated that highly cross-linked polyethylene has
      markedly improved wear resistance compared with conventional polyethylene under a
      variety of conditions. Early clinical data have supported these results. To make
      informed decisions about this already widely available and frequently used
      product, the practicing orthopaedic surgeon should have a basic understanding of
      the production process as well as knowledge of the most current laboratory and
      clinical data.

PMID- 16959888
TI  - Microbial community in a sediment-hosted CO2 lake of the southern Okinawa Trough
      hydrothermal system.
AB  - Increasing levels of CO2 in the atmosphere are expected to cause climatic change
      with negative effects on the earth's ecosystems and human society. Consequently,
      a variety of CO2 disposal options are discussed, including injection into the
      deep ocean. Because the dissolution of CO2 in seawater will decrease ambient pH
      considerably, negative consequences for deep-water ecosystems have been
      predicted. Hence, ecosystems associated with natural CO2 reservoirs in the deep
      sea, and the dynamics of gaseous, liquid, and solid CO2 in such environments, are
      of great interest to science and society. We report here a biogeochemical and
      microbiological characterization of a microbial community inhabiting deep-sea
      sediments overlying a natural CO2 lake at the Yonaguni Knoll IV hydrothermal
      field, southern Okinawa Trough. We found high abundances (>10(9) cm(-3)) of
      microbial cells in sediment pavements above the CO2 lake, decreasing to
      strikingly low cell numbers (10(7) cm(-3)) at the liquid CO2/CO2-hydrate
      interface. The key groups in these sediments were as follows: (i) the anaerobic
      methanotrophic archaea ANME-2c and the Eel-2 group of Deltaproteobacteria and
      (ii) sulfur-metabolizing chemolithotrophs within the Gamma- and
      Epsilonproteobacteria. The detection of functional genes related to one-carbon
      assimilation and the presence of highly 13C-depleted archaeal and bacterial lipid
      biomarkers suggest that microorganisms assimilating CO2 and/or CH4 dominate the
      liquid CO2 and CO2-hydrate-bearing sediments. Clearly, the Yonaguni Knoll is an
      exceptional natural laboratory for the study of consequences of CO2 disposal as
      well as of natural CO2 reservoirs as potential microbial habitats on early Earth
      and other celestial bodies.

PMID- 16959890
TI  - Posttraumatic proximal interphalangeal joint flexion contractures.
AB  - Normal motion of the proximal interphalangeal joint requires bony support, intact
      articular surfaces, unimpeded tendon gliding, and uncompromised integrity of the
      collateral ligaments and volar plate. Deficiency in any one of these structural
      requirements can lead to a loss of finger joint motion and decreased hand
      function. Once finger extension is lost, options include nonsurgical or surgical
      treatment. Nonsurgical treatment such as splinting or serial casting should be
      tried before attempting surgical intervention. When severe flexion deformity
      exists or the vascular status of the finger has been compromised, arthrodesis or
      amputation should be undertaken instead of procedures to regain motion. Surgical
      options for regaining motion include external fixators and open surgical release.
      Although they can lead to improved extension at the proximal interphalangeal
      joint, external fixators carry a risk of reduced finger flexion and pin site
      infection. Most clinical series of patients who have undergone surgical release
      document improvement in flexion contracture between 25 degrees to 30 degrees and
      a shift of the flexion/extension arc into a more functional range. Close follow
      up after surgery is warranted, with frequent physical therapy and splinting.

PMID- 16959891
TI  - Failed back surgery syndrome: diagnostic evaluation.
AB  - Failed back surgery syndrome is a common problem with enormous costs to patients,
      insurers, and society. The etiology of failed back surgery can be poor patient
      selection, incorrect diagnosis, suboptimal selection of surgery, poor technique,
      failure to achieve surgical goals, and/or recurrent pathology. Successful
      intervention in this difficult patient population requires a detailed history,
      precise physical examination, and carefully chosen diagnostic tests. The
      diagnostic evaluation should endeavor to accurately identify symptoms, rule out
      extraspinal causes, identify a specific spinal etiology, and assess the
      psychological state of the patient. Only after these factors have been assessed
      can further treatment be planned.

PMID- 16959892
TI  - Perioperative medication management for the patient with rheumatoid arthritis.
AB  - The treatment of rheumatoid arthritis has improved dramatically in recent years
      with the advent of the latest generation of disease-modifying antirheumatic
      drugs. Despite these advances, in some patients inflammation is not diminished
      sufficiently to prevent irreversible musculoskeletal damage, thus requiring
      surgical intervention to reduce pain and improve function. In these cases, the
      orthopaedic surgeon frequently encounters patients on a drug regimen consisting
      of nonsteroidal anti-inflammatory drugs, glucocorticoids, methotrexate, and
      biologic agents (disease-modifying antirheumatic drugs). Consultation with a
      rheumatologist is recommended, but the surgeon also should be aware of these
      medications that could potentially affect surgical outcome. Prudent perioperative
      management of these drugs is required to optimize surgical outcome. A balance
      must be struck between minimizing potential surgical complications and
      maintaining disease control to facilitate postoperative rehabilitation of
      patients with rheumatoid arthritis.

PMID- 16959893
TI  - Clearing the pediatric cervical spine following injury.
AB  - Injury to the pediatric cervical spine is uncommon; however, a missed or delayed
      diagnosis can lead to disastrous consequences. Thus, following trauma, clearance
      of the pediatric cervical spine is important. Problematic issues include child
      compliance with examination, the complex anatomy of the pediatric cervical spine,
      lack of agreement on definitive imaging modalities, and the coordination of
      multiple medical specialties. Expediting clearance of the pediatric cervical
      spine requires an organized, multidisciplinary approach. In addition to
      systematic procedures within the emergency department, preventing missed and
      delayed diagnoses of cervical spine injury can be facilitated by applying a clear
      methodology for reviewing radiographs in conjunction with the child's clinical
      examination. This algorithm considers the adequacy of the images, alignment of
      the bony and soft-tissue elements, assessment of the cervical intervals, and the
      presence of abnormal angulation. Together with standard treatment, this protocol
      facilitates effective and expeditious clearance of the cervical spine.

PMID- 16959894
TI  - Internal fixation of femoral neck fractures.

PMID- 16959895
TI  - Control of NK cell functions by CD4+CD25+ regulatory T cells.
AB  - Regulatory T cells (Treg) are key players in the maintenance of peripheral
      tolerance. As a result of suppressive effects on CD4+ and CD8+ effector T cells,
      Treg control the adaptive immune system and prevent autoimmunity. In addition,
      they inhibit B lymphocytes, dendritic cells, and monocytes/macrophages. It is
      interesting that several recent papers show that CD4+CD25+ Treg are also able to
      inhibit NK cells. Thus, Treg exert their control on immune responses from the
      onset (triggering of innate immune cells) to the effector phase of adaptive
      immunity (B and T cell-mediated responses). That Treg inhibit NK cells suggests
      that their uncontrolled activation might break self-tolerance and induce "innate"
      autoimmune pathology. Conversely, Treg-mediated suppression of NK cell functions
      might have negative effects, as these cells are important in defense against
      infections and cancer. It is conceivable that Treg might dampen efficient
      activation of NK cells in these diseases.

PMID- 16959896
TI  - Roles of neutrophil-mediated inflammatory response in the bony repair of injured
      growth plate cartilage in young rats.
AB  - Injured growth plate cartilage is often repaired by bony tissue, resulting in
      impaired bone growth in children. Previously, injury-induced, initial
      inflammatory response was shown to be an acute inflammatory event containing
      predominantly neutrophils. To examine potential roles of neutrophils in the bony
      repair, a neutrophil-neutralizing antiserum or control normal serum was
      administered systemically in rats with growth plate injury. The inflammatory
      response was found temporally associated with increased expression of neutrophil
      chemotactic chemokine cytokine-induced neutrophil chemoattractant-1 and cytokines
      TNF-alpha and IL-1beta. Following the inflammatory response, mesenchymal
      infiltration, chondrogenic and osteogenic responses, and bony repair were
      observed at the injury site. Neutrophil reduction did not significantly affect
      infiltration of other inflammatory cells and expression of TNF-alpha and IL-1beta
      and growth factors, platelet-derived growth factor-B and TGF-beta1, at the
      injured growth plate on Day 1 and had no effects on mesenchymal infiltration on
      Day 4. By Day 10, however, there was a significant reduction in proportion of
      mesenchymal repair tissue but an increase (although statistically insignificant)
      in bony trabeculae and a decrease in cartilaginous tissue within the injury site.
      Consistently, in antiserum-treated rats, there was an increase in expression of
      osteoblastic differentiation transcription factor cbf-alpha1 and bone matrix
      protein osteocalcin and a decrease in chondrogenic transcription factor Sox-9 and
      cartilage matrix collagen-II in the injured growth plate. These results suggest
      that injury-induced, neutrophil-mediated inflammatory response appears to
      suppress mesenchymal cell osteoblastic differentiation but enhance chondrogenic
      differentiation, and thus, it may be involved in regulating downstream
      chondrogenic and osteogenic events for growth plate bony repair.

PMID- 16959897
TI  - The Fps/Fes kinase regulates the inflammatory response to endotoxin through down
      regulation of TLR4, NF-kappaB activation, and TNF-alpha secretion in macrophages.
AB  - Fps/Fes and Fer are members of a distinct subfamily of cytoplasmic protein
      tyrosine kinases that have recently been implicated in the regulation of innate
      immunity. Previous studies showed that mice lacking Fps/Fes are hypersensitive to
      systemic LPS challenge, and Fer-deficient mice displayed enhanced recruitment of
      leukocytes in response to local LPS challenge. This study identifies
      physiological, cellular, and molecular defects that contribute to the
      hyperinflammatory phenotype in Fps/Fes null mice. Plasma TNF-alpha levels were
      elevated in LPS challenged Fps/Fes null mice as compared with wild-type mice and
      cultured Fps/Fes null peritoneal macrophages treated with LPS showed increased
      TNF-alpha production. Cultured Fps/Fes null macrophages also displayed prolonged
      LPS-induced degradation of IkappaB-alpha, increased phosphorylation of the p65
      subunit of NF-kappaB, and defective TLR4 internalization, compared with wild-type
      macrophages. Together, these observations provide a likely mechanistic basis for
      elevated proinflammatory cytokine secretion by Fps/Fes null macrophages and the
      increased sensitivity of Fps/Fes null mice to endotoxin. We posit that Fps/Fes
      modulates the innate immune response of macrophages to LPS, in part, by
      regulating internalization and down-regulation of the TLR4 receptor complex.

PMID- 16959898
TI  - Matrix metalloproteinases, their production by monocytes and macrophages and
      their potential role in HIV-related diseases.
AB  - Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are a
      subfamily of metzincins. Matrix metalloproteinases are responsible for much of
      the turnover of extra-cellular matrix components and are key to a wide range of
      processes including tissue remodeling and release of biological factors.
      Imbalance between the MMPs and endogenous tissue inhibitors of metalloproteinases
      (TIMPs) can result in dysregulation of many biologic processes and lead to the
      development of malignancy, cardiovascular disease, and autoimmune and
      inflammatory disorders. MMP production by monocyte/macrophages is dependent on
      the cell type, state of differentiation, and/or level of activation and whether
      they are infected, e.g., by HIV-1. MMP expression by HIV-1 infected monocytes and
      macrophages may alter cellular trafficking and contribute to HIV-associated
      pathology such as HIV-associated dementia (HAD). This review will provide a
      classification of the MMP super-family with particular reference to those
      produced by monocyte/macrophages, describe their regulation and function within
      the immune system, and indicate their possible roles in the pathogenesis of
      disease, including HIV-associated dementia.

PMID- 16959899
TI  - A CD34(+) human cell line model of myeloid dendritic cell differentiation:
      evidence for a CD14(+)CD11b(+) Langerhans cell precursor.
AB  - The study of early events in dendritic cell (DC) differentiation is hampered by
      the lack of homogeneous primary cell systems that allow the study of cytokine
      driven, transitional DC differentiation steps. The CD34(+) acute myeloid leukemia
      cell line MUTZ-3 displays a unique ability to differentiate into interstitial DC
      (IDC) and Langerhans cells (LC) in a cytokine-dependent manner. Phenotypic
      characterization revealed MUTZ-3 to consist of three distinct subpopulations.
      Small CD34(+)CD14(-)CD11b(-) progenitors constitute the proliferative compartment
      of the cell line with the ability to differentiate through a CD34(-)CD14(
      )CD11b(+) stage to ultimately give rise to a morphologically large,
      nonproliferating CD14(+)CD11b(hi) progeny. These CD14(+)CD11b(hi) cells were
      identified as common, immediate myeloid DC precursors with the ability to
      differentiate into LC and IDC, exhibiting characteristic and mutually exclusive
      expression of Langerin and DC-specific ICAM-grabbing nonintegrin, respectively.
      The identity of the MUTZ-3-derived LC subset was confirmed further by the
      presence of Birbeck granules. We conclude that the MUTZ-3 cell line provides a
      ready and continuous supply of common myeloid precursors, which should facilitate
      further study of the ontogeny of myeloid DC lineages.

PMID- 16959900
TI  - Endotoxin tolerance attenuates LPS-induced TLR4 mobilization to lipid rafts: a
      condition reversed by PKC activation.
AB  - Endotoxin tolerance is characterized by attenuated macrophage activation to
      subsequent LPS challenge and can be reversed through nonspecific protein kinase C
      (PKC) activation, and activation by LPS within naive cells requires the
      activation of the cell surface receptors CD14 and TLR4 on lipid rafts. The effect
      of PKC activation and endotoxin tolerance on lipid raft receptor complex assembly
      is unknown and the focus of this study. Tolerance was induced in THP-1 cells
      through LPS pre-exposure. Naive and tolerant cells were stimulated with LPS, with
      or without PMA pretreatment to activate PKC. TLR4 surface expression and LPS
      binding were determined by flow cytometry and immunohistochemistry. Cellular and
      lipid raft protein was analyzed for the presence and activation of the TLR4
      complex components. Harvested supernatants were examined for TNF-alpha
      production. Total TLR4 surface expression and LPS binding were not affected by
      tolerance induction. LPS stimulation of naive cells resulted in TLR4 and heat
      shock protein (HSP)70 lipid raft mobilization, MAPK activation, and TNF-alpha
      production. LPS stimulation of tolerant cells was associated with attenuation of
      all of these cellular events. Although PKC activation by PMA had no effect on
      naive cells, it did result in reversal in tolerance-induced suppression of TLR4
      and HSP70 lipid raft mobilization, MAPK activation, and TNF-alpha production. In
      addition, the effects associated with PMA were reversed with exposure to a
      myristoylated PKC-zeta pseudosubstrate. Thus, endotoxin tolerance appears to be
      induced through attenuated TLR4 formation following LPS stimulation. This complex
      formation appears to be PKC-dependent, and restoration of PKC activity reverses
      tolerance.

PMID- 16959901
TI  - Clathrin-associated adaptor protein complexes.

PMID- 16959902
TI  - Integrin traffic.
AB  - Cell adhesion, migration and the maintenance of cell polarity are all processes
      that depend on the correct targeting of integrins and the dynamic remodelling of
      integrin-containing adhesion sites. The importance of the endo/exocytic cycle of
      integrins as a key regulator of these functions is increasingly recognized.
      Several recent publications have provided mechanistic insight into how integrin
      traffic is regulated in cells. Increasing evidence suggests that small GTPases
      such as Arf6 and members of the Rab family control integrin internalization and
      recycling back to the plasma membrane along microtubules. The fine tuning of
      these trafficking events seems to be mediated by specific guanine-nucleotide
      exchange factors (GEFs) and GTPase-activating proteins (GAPs). In addition,
      several kinases regulate integrin traffic. The identification of their substrates
      has demonstrated how these kinases regulate integrin traffic by controlling small
      GTPases or stabilizing cytoskeletal tracks that are crucial for efficient traffic
      of integrins to the plasma membrane.

PMID- 16959903
TI  - Syntaxin 1A promotes the endocytic sorting of EAAC1 leading to inhibition of
      glutamate transport.
AB  - The neuronal glutamate transporter, excitatory amino-acid carrier 1 (EAAC1),
      plays an important role in the modulation of neurotransmission and contributes to
      synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and
      to epileptogenesis. However, the mechanisms that regulate EAAC1 endocytic sorting
      and function remain largely unknown. Here, we first demonstrate that EAAC1
      undergoes internalization through the clathrin-mediated pathway and further show
      that syntaxin 1A, a key molecule in synaptic exocytosis, potentiates EAAC1
      internalization, thus leading to the functional inhibition of EAAC1. In the
      presence of the transmembrane domain of syntaxin 1A, its H3 coiled-coil domain of
      syntaxin 1A is necessary and sufficient for the inhibition of EAAC1. Furthermore,
      specific suppression of endogenous syntaxin 1A significantly blocked EAAC1
      endocytic sorting and lysosomal degradation promoted by kainic acid, a drug for
      kindling the animal model of human temporal lobe epilepsy in rat, indicating a
      potential role of syntaxin 1A in epileptogenesis. These findings provide new
      evidence that syntaxin 1A serves as an intrinsic enhancer to EAAC1 endocytic
      sorting and further suggest that syntaxin 1A is conversant with both ;ins' and
      ;outs' of synaptic neurotransmission.

PMID- 16959904
TI  - Functional dissection of the Tol2 transposable element identified the minimal cis
      sequence and a highly repetitive sequence in the subterminal region essential for
      transposition.
AB  - The Tol2 element is a naturally occurring active transposable element found in
      vertebrate genomes. The Tol2 transposon system has been shown to be active from
      fish to mammals and considered to be a useful gene transfer vector in
      vertebrates. However, cis-sequences essential for transposition have not been
      characterized. Here we report the characterization of the minimal cis-sequence of
      the Tol2 element. We constructed Tol2 vectors containing various lengths of DNA
      from both the left (5') and the right (3') ends and tested their transpositional
      activities both by the transient excision assay using zebrafish embryos and by
      analyzing chromosomal transposition in the zebrafish germ lineage. We
      demonstrated that Tol2 vectors with 200 bp from the left end and 150 bp from the
      right end were capable of transposition without reducing the transpositional
      efficiency and found that these sequences, including the terminal inverted
      repeats (TIRs) and the subterminal regions, are sufficient and required for
      transposition. The left and right ends were not interchangeable. The Tol2 vector
      carrying an insert of >11 kb could transpose, but a certain length of spacer,
      <276 but >18 bp, between the left and right ends was necessary for excision.
      Furthermore, we found that a 5-bp sequence, 5'-(A/G)AGTA-3', is repeated 33 times
      in the essential subterminal region. Mutations in the repeat sequence at 13
      different sites in the subterminal region, as well as mutations in TIRs, severely
      reduced the excision activity, indicating that they play important roles in
      transposition. The identification of the minimal cis-sequence of the Tol2 element
      and the construction of mini-Tol2 vectors will facilitate development of useful
      transposon tools in vertebrates. Also, our study established a basis for further
      biochemical and molecular biological studies for understanding roles of the
      repetitive sequence in the subterminal region in transposition.

PMID- 16959905
TI  - Focal warming in the nucleus of the solitary tract prolongs the laryngeal
      chemoreflex in decerebrate piglets.
AB  - The laryngeal chemoreflex (LCR), elicited by a drop of water in the larynx, is
      exaggerated by mild hyperthermia (body temperature = 40-41 degrees C) in neonatal
      piglets. We tested the hypothesis that thermal prolongation of the LCR results
      from heating the nucleus of the solitary tract (NTS), where laryngeal afferents
      first form synapses in the brain stem. Three- to 13-day-old piglets were
      decerebrated and vagotomized and studied without anesthesia while paralyzed and
      ventilated. Phrenic nerve activity and rectal temperature were recorded. A
      thermode was placed in the medulla, and the brain tissue temperature was recorded
      with a thermistor approximately 1 mm from the tip of the thermode. When the
      thermode was inserted into the brain stem, respiratory activity was arrested or
      greatly distorted in eight animals. However, the thermode was inserted in nine
      animals without disrupting respiratory activity, and in these animals, warming
      the medullary thermode (thermistor temperature = 40-41 degrees C) while holding
      rectal temperature constant reversibly exaggerated the LCR. The caudal raphe was
      warmed focally by approximately 2 degrees C in four additional animals; this did
      not alter the duration of the LCR in these animals. Thermodes placed in the NTS
      did not disrupt respiratory activity, but they did prolong the LCR when warmed.
      Thermodes that were placed deep to the NTS in the region of the nucleus ambiguus
      disrupted respiratory activity, which precluded any analysis of the LCR. We
      conclude that prolongation of the laryngeal chemoreflex by whole body
      hyperthermia originates from the elevation of brain tissue temperature within in
      the NTS.

PMID- 16959906
TI  - Vigilance state-dependent attenuation of hypercapnic chemoreflex and exaggerated
      sleep apnea in orexin knockout mice.
AB  - Exogenous administration of orexin can promote wakefulness and respiration. Here
      we examined whether intrinsic orexin participates in the control of breathing in
      a vigilance state-dependent manner. Ventilation was recorded together with
      electroencephalography and electromyography for 6 h during the daytime in prepro
      orexin knockout mice (ORX-KO) and wild-type (WT) littermates. Respiratory
      parameters were separately determined during quiet wakefulness (QW), slow-wave
      sleep (SWS), or rapid eye movement (REM) sleep. Basal ventilation was normal in
      ORX-KO, irrespective of vigilance states. The hypercapnic ventilatory response
      during QW in ORX-KO (0.19 +/- 0.01 ml.min(-1).g(-1).%CO(2)(-1)) was significantly
      smaller than that in WT mice (0.38 +/- 0.04 ml.min(-1).g(-1).%CO(2)(-1)), whereas
      the responses during SWS and REM in ORX-KO were comparable to those in WT mice.
      Hypoxic responses during wake and sleep periods were not different between the
      genotypes. Spontaneous but not postsigh sleep apneas were more frequent in ORX-KO
      than in WT littermates during both SWS and REM sleep. Our findings suggest that
      orexin plays a crucial role both in CO(2) sensitivity during wakefulness and in
      preserving ventilation stability during sleep.

PMID- 16959907
TI  - Anticipatory responses of catecholamines on muscle force production.
AB  - Few data exist on the temporal relationship between catecholamines and muscle
      force production in vivo. The purpose of this study was to examine the influence
      of preexercise arousal on sympathoadrenal neurohormones on muscular force
      expression during resistance exercise. Ten resistance-trained men completed two
      experimental conditions separated by 7 days: 1) acute heavy resistance exercise
      protocol (AHREP; 6 x 10 repetitions parallel squats, 80% 1 repetition maximum)
      and 2) control (Cont; rest). Peak force (F(peak)) was recorded during a maximal
      isometric squat preceding each set and mean force (F(mean)) was measured during
      each set. Serial venous blood samples were collected before the AHREP and
      immediately preceding each set. Blood collection times were matched during Cont.
      Preexercise epinephrine (Epi), norepinephrine (NE), and dopamine (DA) increased
      (P <or= 0.05) above Cont by 270, 255, and 164%, respectively. During exercise,
      Epi, NE, and DA continued to increase by 512, 271, and 38%, respectively, above
      preexercise values. F(peak) and F(mean) decreased by approximately 20-25% over
      the course of the AHREP. Post hoc data analysis revealed that five subjects
      (F(maintainers)) showed no decline (P >or= 0.05) in muscular performance
      (F(peak), F(mean)) during AHREP and that five subjects (F(reducers)) had
      significant reductions in F(peak) and F(mean). Integrated area under the curve
      for Epi, NE, and F(peak) were greater (P < 0.02) for F(maintainers) than
      F(reducers). In conclusion, an anticipatory rise in catecholamines existed, which
      may be essential for optimal force production at the onset of exercise.

PMID- 16959908
TI  - Bicarbonate infusion and pH clamp moderately reduce hyperventilation during ramp
      exercise in humans.
AB  - To test the hypothesis that the decrease in plasma pH contributes to the
      hyperventilation observed in humans in response to exercise at high workloads,
      five healthy male subjects performed a ramp exercise [maximal workload: 352 W (SD
      35)] in a control situation and when arterialized plasma pH was maintained at the
      resting level (pH clamp) by intravenous infusion of sodium bicarbonate [129 mmol
      (SD 23), beginning at 59% maximal workload (SD 5)]. Bicarbonate infusion did not
      modify O(2) consumption (Vo(2)) but significantly (P < 0.05) increased arterial
      Pco(2), plasma bicarbonate concentration, and respiratory exchange ratio (P <
      0.05). At the three highest workloads, pulmonary ventilation (Ve) and Ve/Vo(2)
      were approximately 5-10% lower (P < 0.05) when bicarbonate was infused than in
      the control situation, and hyperventilation was reduced by 15-30%. These data
      suggest that the decrease in plasma pH is one of the factors that contribute to
      the hyperventilation observed at high workloads.

PMID- 16959910
TI  - Modulation of motor unit firing rates during a complex sinusoidal force task in
      young and older adults.
AB  - This study compared motor unit rate coding and muscular force control in the
      first dorsal interosseous muscle of older (n = 11, mean 72.3 yr) and young (n =
      12, mean 18.7 yr) adults. Rate coding during a sinusoidal isometric force
      matching task was evaluated using spectral analysis of the time-varying changes
      in firing rate. The task required force modulations to match a trajectory
      comprising the sum of 0.15- and 0.45-Hz sine waves. Based on the amplitude of
      spectral peaks at 0.15 and 0.45 Hz, the amplitude of force modulation was similar
      in young and older adults at both frequencies (F = 1.9, P = 0.17). Force
      modulation gain (FMG) was computed as the ratio of the amplitude of force
      modulation to the amplitude of firing rate modulation. To account for rate coding
      differences related to the properties of the motoneuron, recruitment threshold
      force was used as a covariate in age-group comparisons. At both task frequencies,
      firing rate was modulated with less amplitude (F = 0 14, P < 0.001) and FMG was
      greater (F = 0 27, P < 0.001) in the older adults. In its transformation of
      neural input to mechanical output, muscle is known to act as a low-pass filter.
      Compared with modulation at 0.15 Hz, less change in force per change in firing
      rate at 0.45 Hz (lower FMG; F = 0 67, P < 0.001), independent of age group, is
      consistent with this filtering effect. Our conclusion is that there is a reduced
      amplitude of firing rate modulation in older adults.

PMID- 16959909
TI  - Motor training induces experience-specific patterns of plasticity across motor
      cortex and spinal cord.
AB  - The motor cortex and spinal cord possess the remarkable ability to alter
      structure and function in response to differential motor training. Here we review
      the evidence that the corticospinal system is not only plastic but that the
      nature and locus of this plasticity is dictated by the specifics of the motor
      experience. Skill training induces synaptogenesis, synaptic potentiation, and
      reorganization of movement representations within motor cortex. Endurance
      training induces angiogenesis in motor cortex, but it does not alter motor map
      organization or synapse number. Strength training alters spinal motoneuron
      excitability and induces synaptogenesis within spinal cord, but it does not alter
      motor map organization. All three training experiences induce changes in spinal
      reflexes that are dependent on the specific behavioral demands of the task. These
      results demonstrate that the acquisition of skilled movement induces a
      reorganization of neural circuitry within motor cortex that supports the
      production and refinement of skilled movement sequences. We present data that
      suggest increases in strength may be mediated by an increased capacity for
      activation and/or recruitment of spinal motoneurons while the increased metabolic
      demands associated with endurance training induce cortical angiogenesis. Together
      these results show the robust pattern of anatomic and physiological plasticity
      that occurs within the corticospinal system in response to differential motor
      experience. The consequences of such distributed, experience-specific plasticity
      for the encoding of motor experience by the motor system are discussed.

PMID- 16959911
TI  - Dependence of lung injury on surface tension during low-volume ventilation in
      normal open-chest rabbits.
AB  - To evaluate the role of pulmonary surfactant in the prevention of lung injury
      caused by mechanical ventilation (MV) at low end-expiratory volumes, lung
      mechanics and morphometry were assessed in three groups of eight normal, open
      chest rabbits ventilated for 3-4 h at zero end-expiratory pressure (ZEEP) with
      physiological tidal volumes (Vt = 10 ml/kg). One group was left untreated (group
      A); the other two received surfactant intratracheally (group B) or aerosolized
      dioctylsodiumsulfosuccinate (group C) before MV on ZEEP. Relative to initial MV
      on positive end-expiratory pressure (PEEP; 2.3 cmH(2)O), quasi-static elastance
      (Est) and airway (Rint) and viscoelastic resistance (Rvisc) increased on ZEEP in
      all groups. After restoration of PEEP, only Rint (124%) remained elevated in
      group A, only Est (36%) was significantly increased in group B, whereas in group
      C, Est, Rint, and Rvisc were all markedly augmented (274, 253, and 343%). In
      contrast, prolonged MV on PEEP had no effect on lung mechanics of eight open
      chest rabbits (group D). Lung edema developed in group C (wet-to-dry ratio =
      7.1), but not in the other groups. Relative to group D, both groups A and C, but
      not B, showed histological indexes of bronchiolar injury, whereas all groups
      exhibited an increased number of polymorphonuclear leukocytes in alveolar septa,
      which was significantly greater in group C. In conclusion, administration of
      exogenous surfactant largely prevents the histological and functional damage of
      prolonged MV at low lung volumes, whereas surfactant dysfunction worsens the
      functional alterations, also because of edema formation and, possibly, increased
      inflammatory response.

PMID- 16959912
TI  - Mechanical response to methacholine and deep inspiration in supine men.
AB  - The effects of supine posture on airway responses to inhaled methacholine and
      deep inspiration (DI) were studied in seven male volunteers. On a control day,
      subjects were in a seated position during both methacholine inhalation and lung
      function measurements. On a second occasion, the whole procedure was repeated
      with the subjects lying supine for the entire duration of the study. On a third
      occasion, methacholine was inhaled from the seated position and measurements were
      taken in a supine position. Finally, on a fourth occasion, methacholine was
      inhaled from the supine position and measurements were taken in the seated
      position. Going from sitting to supine position, the functional residual capacity
      decreased by approximately 1 liter in all subjects. When lung function
      measurements (pulmonary resistance, dynamic elastance, residual volume, and
      maximal flows) were taken in supine position, the response to methacholine was
      greater than at control, and this was associated with a greater dyspnea and a
      faster recovery of dynamic elastance after DI. By contrast, when methacholine was
      inhaled in supine position but measurements were taken in sitting position, the
      response to methacholine was similar to control day. These findings document the
      potential of the decrease in the operational lung volumes in eliciting or
      sustaining airflow obstruction in nocturnal asthma. It is speculated that the
      exaggerated response to methacholine in the supine posture may variably
      contribute to airway smooth muscle adaptation to short length, airway wall edema,
      and faster airway renarrowing after a large inflation.

PMID- 16959913
TI  - Ia-afferent input to motoneurons during shortening and lengthening muscle
      contractions in humans.
AB  - The central nervous system employs different strategies to execute specific motor
      tasks. Because afferent feedback during shortening and lengthening muscle
      contractions differs, the neural strategy underlying these tasks may be quite
      distinct. Cortical drive may be adjusted or afferent input regulated. The exact
      mechanisms are not clear. Here, we examine the control of synaptic transmission
      across the Ia synapse during shortening and lengthening muscle contractions.
      Subjects were instructed to maintain isolated activity in a single tibialis
      anterior (TA) motor unit while muscle length was varied from flexion to extension
      and back. At a fixed interval after a firing of the active motor unit, a single
      electrical stimulus was applied to the common peroneal nerve to activate Ia
      afferents from the TA muscle. We investigated the stimulus-induced change in
      firing probability of 19 individual low-threshold TA motor units during
      shortening and lengthening contractions. Any change in firing probability depends
      on both pre- and postsynaptic mechanisms. In this experiment, motoneuron firing
      rate was similar during both contraction types. There was no difference in the
      firing probability between shortening and lengthening contractions (0.23 +/- 0.03
      and 0.20 +/- 0.02, respectively). We suggest that there is no contraction type
      specific control of Ia input to the motoneurons during shortening and lengthening
      muscle contractions. Cortical adjustments may have occurred.

PMID- 16959914
TI  - Effects of pulse lung inflation on chest wall expiratory motor activity.
AB  - The effects of pulse lung inflation (LI) on expiratory muscle activity and phase
      duration (Te) were determined in anesthetized, spontaneously breathing dogs (n =
      20). A volume syringe was used to inflate the lungs at various times during the
      expiratory phase. The magnitude of lung volume was assessed by the corresponding
      change in airway pressure (Paw; range 2-20 cmH(2)O). Electromyographic (EMG)
      activities were recorded from both thoracic and abdominal muscles. Parasternal
      muscle EMG was used to record inspiratory activity. Expiratory activity was
      assessed from the triangularis sterni (TS), internal intercostal (IIC), and
      transversus abdominis (TA) muscles. Lung inflations <7 cmH(2)O consistently
      inhibited TS activity but had variable effects on TA and IIC activity and
      expiratory duration. Lung inflations resulting in Paw values >7 cmH(2)O, however,
      inhibited expiratory EMG activity of each of the expiratory muscles and
      lengthened Te in all animals. The responses of expiratory EMG and Te were
      directly related to the magnitude of the lung inflation. The inhibition of
      expiratory motor activity was independent of the timing of pulse lung inflation
      during the expiratory phase. The inhibitory effects of lung inflation were
      eliminated by bilateral vagotomy and could be reproduced by electrical
      stimulation of the vagus nerve. We conclude that pulse lung inflation resulting
      in Paw between 7 and 20 cmH(2)O produces a vagally mediated inhibition of
      expiratory muscle activity that is directly related to the magnitude of the
      inflation. Lower inflation pressures produce variable effects that are muscle
      specific.

PMID- 16959915
TI  - Maintenance of end-expiratory recruitment with increased respiratory rate after
      saline-lavage lung injury.
AB  - Cyclical recruitment of atelectasis with each breath is thought to contribute to
      ventilator-associated lung injury. Extrinsic positive end-expiratory pressure
      (PEEPe) can maintain alveolar recruitment at end exhalation, but PEEPe depresses
      cardiac output and increases overdistension. Short exhalation times can also
      maintain end-expiratory recruitment, but if the mechanism of this recruitment is
      generation of intrinsic PEEP (PEEPi), there would be little advantage compared
      with PEEPe. In seven New Zealand White rabbits, we compared recruitment from
      increased respiratory rate (RR) to recruitment from increased PEEPe after saline
      lavage. Rabbits were ventilated in pressure control mode with a fraction of
      inspired O(2) (Fi(O(2))) of 1.0, inspiratory-to-expiratory ratio of 2:1, and
      plateau pressure of 28 cmH(2)O, and either 1) high RR (24) and low PEEPe (3.5) or
      2) low RR (7) and high PEEPe (14). We assessed cyclical lung recruitment with a
      fast arterial Po(2) probe, and we assessed average recruitment with blood gas
      data. We measured PEEPi, cardiac output, and mixed venous saturation at each
      ventilator setting. Recruitment achieved by increased RR and short exhalation
      time was nearly equivalent to recruitment achieved by increased PEEPe. The short
      exhalation time at increased RR, however, did not generate PEEPi. Cardiac output
      was increased on average 13% in the high RR group compared with the high PEEPe
      group (P < 0.001), and mixed venous saturation was consistently greater in the
      high RR group (P < 0.001). Prevention of end-expiratory derecruitment without
      increased end-expiratory pressure suggests that another mechanism, distinct from
      intrinsic PEEP, plays a role in the dynamic behavior of atelectasis.

PMID- 16959916
TI  - Antioxidants increase the ventilatory response to hyperoxic hypercapnia.
AB  - RATIONALE: The mechanisms by which chemoreceptors process carbon dioxide stimuli
      are poorly understood. Recent in vitro studies suggest a role of reactive oxygen
      species in central carbon dioxide chemoreception. OBJECTIVES: We tested the
      hypothesis that antioxidant treatment modulates the ventilatory response to
      carbon dioxide in healthy humans, either during unloaded breathing or after
      strenuous resistive breathing. METHODS: In the first experiment of this
      randomized, double-blind, placebo-controlled study, 14 healthy males completed
      hyperoxic carbon dioxide rebreathing, received either antioxidants (vitamins E,
      A, and C for 2 mo, allopurinol for 15 d, and N-acetylcysteine for 3 d) (n = 7) or
      placebo (n = 7), and repeated rebreathing 3 mo later. In the second experiment,
      18 healthy males completed a series of rebreathing tests before and after
      strenuous resistive breathing. Subjects repeated the same protocol 3 mo later,
      after they had received antioxidants (n = 9) or placebo (n = 9). MAIN RESULTS:
      After antioxidants, the sensitivity of the ventilatory (minute ventilation)
      response to carbon dioxide increased (mean [+/- SEM], 3.2 +/- 0.5 vs. 1.7 +/- 0.4
      L/min/mm Hg; p < 0.001). Antioxidants also increased the sensitivity to carbon
      dioxide before and at 5, 30, and 120 min after resistive breathing (p = 0.01).
      This effect was entirely due to increased tidal volume. Antioxidants did not
      influence the breathing pattern during resting breathing or the rapid shallow
      breathing response to carbon dioxide at 5 min after resistive breathing.
      CONCLUSIONS: Antioxidants, by augmenting the tidal volume, increase the
      sensitivity of the ventilatory response to carbon dioxide, either during unloaded
      breathing or after resistive breathing.

PMID- 16959917
TI  - Inflammatory lung secretions inhibit dendritic cell maturation and function via
      neutrophil elastase.
AB  - RATIONALE: Continuous episodes of infection are a feature of lung diseases such
      as chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). Lung
      antigen-presenting dendritic cells (DCs) sample inhaled antigen to initiate
      immune responses. Therefore, we hypothesized that inflammatory mediators, such as
      neutrophil elastase (NE) released into the lung, may be able to modulate their
      activity. OBJECTIVE: To determine whether sputum (from patients with COPD and
      those with CF) or NE can alter DC phenotype and function. METHOD: NE and sputum
      samples were incubated with immature or mature murine DCs (mDCs). DC phenotype
      and function were studied by fluorescence-activated cell sorter and Western Blot
      analysis, assessing their expression of costimulatory molecules and their ability
      to induce T cell proliferation. RESULTS: COPD/CF sputum samples and human NE
      downregulated the expression of CD40, CD80, and CD86 (but not major
      histocompatibility complex II) on DCs and inhibited LPS-induced DC maturation.
      This effect was partially (sputa) to significantly (NE) reversed by addition of
      recombinant secretory leukocyte protease inhibitor. Western Blot analysis showed
      that purified NE degraded CD86 in mDC lysates in a time- and dose-dependent
      fashion, and caused shedding of CD86 into the supernatants of mDC cultures. NE
      treatment also inhibited the antigen-presenting ability of mDCs, as measured by
      their ability to induce ovalbumin-specific D011.10-transgenic T-cell
      proliferation. CONCLUSIONS: Our data indicate that NE in lung inflammatory
      secretions of patients with COPD/CF may disable DCs and prevent them from
      mounting an adequate immune response. This may have implications for the
      infection-driven generation of disease exacerbations in these two pathologies.

PMID- 16959918
TI  - Effect of allergic bronchopulmonary aspergillosis on lung function in children
      with cystic fibrosis.
AB  - RATIONALE: The relationship between sensitization to Aspergillus fumigatus and
      progression of pulmonary function is not yet established in cystic fibrosis (CF).
      OBJECTIVES: We aimed to evaluate onset of A. fumigatus sensitization and
      development of allergic bronchopulmonary aspergillosis (ABPA), as well as to
      determine the physiologic factors of lung function influencing these mechanisms
      in CF. METHODS: Serial annual lung function tests performed in 122 children with
      CF (62 males; 60 females; age: 6-18 yr) provided data pertaining to FRC measured
      by plethysmography, lung clearance index, volume of trapped gas, effective
      specific airway resistance, and forced expiratory indices (FEV1, FEF at 50% VC).
      Specific IgE to recombinant A. fumigatus allergens, rAspf1 and rAspf3, served as
      marker for sensitization, and to rAspf4 and rAspf6 as indications for a serologic
      ABPA, were clinically diagnosed (Nelson criteria). By linear mixed-effect model
      analysis, five patient groups, (1) not sensitized and free from Pseudomonas
      aeruginosa, (2) intermittently P. aeruginosa colonized, (3) chronically P.
      aeruginosa infected, (4) sensitized, and (5) with ABPA, were retrospectively
      evaluated. MEASUREMENTS AND MAIN RESULTS: A. fumigatus sensitization was best
      reflected by increased rAspf1+3-specific IgE levels, whereas, in most patients,
      sensitization was preceded by P. aeruginosa infection. Patients with ABPA
      demonstrated the most severe progression in all lung function parameters, and FEF
      at 50% VC, volume of trapped gas, and effective specific airway resistance were
      the best predictors (p < 0.0001). However, regarding distinction between
      sensitization to A. fumigatus and development of ABPA in the course of CF,
      chronic P. aeruginosa infection has to be taken into account. CONCLUSIONS: Airway
      narrowing, gas trapping, and small airway disease are the major targets for
      functional derangement in ABPA.

PMID- 16959919
TI  - Airway smooth muscle and mast cell-derived CC chemokine ligand 19 mediate airway
      smooth muscle migration in asthma.
AB  - RATIONALE: Airway smooth muscle (ASM) hyperplasia is a feature of asthma, and
      increases with disease severity. We hypothesized that this results from migration
      of ASM or progenitors in response to chemokines derived from ASM or mast cells
      within the ASM bundle. OBJECTIVES: To examine expression of the chemokine
      receptor, CC chemokine receptor (CCR) 7, in vivo by ASM in patients with asthma
      and healthy control subjects, and by primary cultures of ASM and fibroblasts; to
      define expression of its ligands, CC chemokine ligand (CCL) 19 and CCL21, in
      bronchial biopsies, and primary cultures of ASM and mast cells; and to
      investigate CCR7's role in ASM migration and repair. METHODS: ASM was isolated
      from bronchoscopy and resection tissue. Receptor and chemokine expression was
      examined by immunohistochemistry, immunofluorescence, flow cytometry, ELISA, and
      reverse transcriptase-polymerase chain reaction. CCR7 function was examined by
      intracellular calcium measurements, chemotaxis, wound healing assays, and
      measurement of cell proliferation. MEASUREMENTS AND MAIN RESULTS: ASM,
      myofibroblasts, and fibroblasts expressed CCR7. CCL19, but not CCL21, was highly
      expressed in bronchial biopsies by mast cells and vessels in asthma of all
      severities, ASM in severe disease, and ex vivo ASM and mast cells. ASM CCR7
      activation by CCL19-mediated intracellular calcium elevation and concentration
      dependent migration, but not proliferation. Importantly, mast cell and ASM
      derived CCL19 mediated ASM migration and repair. CONCLUSIONS: The CCL19/CCR7 axis
      may play an important role in the development of ASM hyperplasia in asthma.

PMID- 16959920
TI  - Fibroblasts in focus.

PMID- 16959921
TI  - Are there more lungs available than currently meet the eye?

PMID- 16959922
TI  - Comments on the updated Harvard Six Cities study.

PMID- 16959923
TI  - Tracheal collapse versus tracheobronchomalacia: normal function versus disease.

PMID- 16959924
TI  - Differences in characteristics and outcome of delirium as based on referral
      patterns.
AB  - The authors studied factors associated with referral of delirium patients to
      psychiatry consultation and its outcome implications. Characteristics and
      treatment outcomes of delirium patients referred to psychiatry were compared with
      those not referred. Referred patients were younger, had a more hyperactive
      subtype, greater substance abuse, less comorbid dementia, were more likely to be
      recognized as having delirium, and be prescribed medications. Improvement in
      referred patients was indicated by lower readmission rate postdischarge. No
      differences were noted in length of stay, discharge status, or mortality within 1
      year of the index episode. Psychiatric interventions were moderately helpful.
      Patients' characteristics and delirium subtypes may influence referral and should
      inform future liaison efforts.

PMID- 16959926
TI  - Aripiprazole in the treatment of delirium.
AB  - Antipsychotic drugs are the primary treatment for symptoms of delirium, but their
      side effects can be problematic. Treatment of delirium with aripiprazole has yet
      to be evaluated. The authors report on 14 patients with delirium treated with
      aripiprazole. Twelve patients had a >or=50% reduction in Delirium Rating Scale,
      Revised-98 scores, and 13 showed improvement on Clinical Global Impression scale
      scores. There was a low rate of adverse side effects. Aripiprazole may be an
      appropriate first-line agent for the treatment of delirium because of its minimal
      effect on QTc interval, weight, lipids, and glucose levels. Controlled comparison
      studies should be performed to confirm this impression.

PMID- 16959925
TI  - The diagnosis of major depression in patients with cancer: a comparative
      approach.
AB  - Depressive symptoms not only impair quality of life in cancer patients but
      constitute an independent risk factor for increased mortality. In order to
      accurately and efficiently identify depression in cancer patients, the authors
      developed a biostatistical strategy to identify items of the 21-item, observer
      rated Hamilton Rating Scale for Depression (Ham-D) that would optimize the
      diagnosis of depression among cancer patients. Exhibiting a relatively high
      sensitivity and specificity, our most optimal diagnostic tool contained six Ham-D
      items (late insomnia, agitation, psychic anxiety, diurnal mood variation,
      depressed mood, and genital symptoms). This study may serve as a prototype to
      generate valid instruments accurate for the diagnosis of major depression in
      other populations of cancer patients.

PMID- 16959927
TI  - Somatic complaints in primary care: further examining the validity of the Patient
      Health Questionnaire (PHQ-15).
AB  - The authors examined the reliability and validity of the PHQ-15, a measure of
      current somatic complaints. An index of medically unexplained symptoms was used
      as a key criterion. Data were utilized from medical outpatients enrolled in a
      treatment study for moderate-to-severe somatization (N=172). Approximately 68% of
      the sample was Hispanic. Results showed that the PHQ-15 was moderately related to
      a history of medically unexplained symptoms among non-Hispanic participants.
      Results indicated ethnic differences on the validity profile of the PHQ-15
      showing that the criterion variables were less predictive of the PHQ-15 among
      Hispanics than among non-Hispanics. Also, among the Hispanic group, the PHQ-15
      was less related to medically unexplained symptoms and more to psychiatric
      distress. General support was provided for using the PHQ-15 with clinical samples
      composed of non-Hispanics. Also, the PHQ-15 appears to measure medically
      unexplained symptoms, psychiatric distress, and physical functioning. Further
      study is recommended to better evaluate ethnic variations and other types of
      validity for the PHQ-15.

PMID- 16959928
TI  - Epidemiology of depression and antidepressant therapy after acute respiratory
      failure.
AB  - The authors enrolled 277 subjects with acute respiratory failure to describe the
      epidemiology of depressive disorders and antidepressant use during and after
      intensive care. By SCID criteria, the prevalence of major depressive episode at 2
      months was 16%, and 16% had depressive disorder not otherwise specified. Mood
      disorder incidence was 25% or 28%, depending on methodology. Pre-ICU physical
      functioning and depression were associated with 2- and 6-month depression
      severity. At 2 months, the prevalence of antidepressant medication use was 49%,
      and the incidence was 28%. Depression and antidepressant pharmacotherapy are
      frequent during recovery from acute respiratory failure.

PMID- 16959929
TI  - Ethnicity and use of alternative products in psychiatric patients.
AB  - The use of herbal and natural products for medical purposes is common in all
      human civilizations, and use in Western societies has grown considerably in
      recent years. However, differences in usage patterns between different ethnic
      groups are yet to be delineated. The current study examined the frequency and
      type of complementary/alternative medications used by a sample of 453 rural
      psychiatric outpatients of two different ethnic groups. The products were
      classified as "natural" (herbal products requiring some preparation before
      consumption) and "processed" (products in "ready-to-use" form). There were
      significant ethnic differences in usage patterns of the various preparations:
      Hispanics, relative to Caucasians, were twice as likely to use natural products,
      whereas Caucasians were more likely than Hispanics to use processed products. The
      symptoms addressed were predominantly psychiatric, with natural products, and
      nonpsychiatric, with processed products. These results may increase awareness
      among healthcare providers regarding the usage frequency of such
      complementary/alternative medications products and the different usage patterns
      across ethnic groups.

PMID- 16959930
TI  - Cognitive-disorder diagnoses in inpatient psychosomatic-medicine consultations:
      associations with age and length of stay.
AB  - Authors reviewed consecutive charts of 155 cognitive-disorder patients from a
      psychosomatic medicine service in 2001, analyzing factors of age, cognitive
      disorder diagnosis, and length of stay. Mean length of stay for this cohort
      exceeded the typical hospital length of stay, and decreased with age. Increased
      age was associated with a decreased probability of a delirium-only diagnosis, and
      was strongly associated with an increased probability of a dementia diagnosis.
      Among those with dementia, the probability of having an additional diagnosis of
      delirium was unrelated to age. The case-mix of cognitive disorders differs with
      age, whereas cognitive disorders are associated with increased length of stay for
      adult patients of all ages.

PMID- 16959931
TI  - Effectiveness of post-discharge case management in general-medical outpatients: a
      randomized, controlled trial.
AB  - This study was initiated to determine the impact of post-discharge, nurse-led,
      home-based case management intervention on the number of emergency readmissions,
      level of care utilization, quality of life, and psychological functioning.
      Patients discharged home from a general hospital (N=147) were randomly assigned
      to usual care or nurse-led, home-based, case management intervention. During the
      24 weeks of follow-up, no difference between the two groups was found for
      readmission, care utilization, quality of life, or psychological functioning.
      Patients in the control group tended to move sooner to non-independent living
      accommodation than patients in the nurse-led, home-based, case management
      intervention group.

PMID- 16959932
TI  - Psychological and social factors that correlate with dyspnea in heart failure.
AB  - Dyspnea is a common symptom of heart failure frequently relied upon to assess
      clinical functioning. The purpose of this study is to explore a broad range of
      medical, psychological, and social factors that correlate with dyspnea in heart
      failure patients. Seventy-six participants ranged from well-compensated,
      ambulatory subjects to those with recent hospitalization for acutely
      decompensated heart failure. The sample was predominantly male, mean age of 63.5
      years, with mild depressive symptoms in 25%. Correlation analysis revealed that
      dyspnea significantly correlated with depression, fatigue, and overall health
      perception. Standard regression analyses indicated that depression, fatigue, and
      overall health perception uniquely contributed to dyspnea, explaining 38.0% of
      the total variance. The present study confirms that dyspnea is multifactorial,
      with links to psychological distress and overall health perception.

PMID- 16959933
TI  - The relationship of medical comorbidity and depression in older, primary care
      patients.
AB  - Comorbid medical illnesses are a key feature of geriatric mood disorders, yet the
      specificity of such associations remains unclear. In a sample of 546 primary care
      patients age >or=65 years, pathology in several organ systems (respiratory,
      eye/ear/nose/throat, gastrointestinal, central nervous system, endocrine) and
      several chronic conditions (neurological disease, low vision, chronic obstructive
      pulmonary disease, diabetes) were associated with depression. However,
      notwithstanding these specific associations, global (overall) medical burden was
      most powerfully and independently associated with depression, largely independent
      of functional status. This generates the hypothesis that, in general primary care
      populations, the relationship of medical illness to depression may be multimodal
      and/or may involve shared pathobiological or psychosocial mechanisms.

PMID- 16959934
TI  - Mirtazapine for severe gastroparesis unresponsive to conventional prokinetic
      treatment.
AB  - Gastroparesis is a condition of abnormal gastric motility characterized by
      delayed gastric emptying without evidence of mechanical outlet obstruction. The
      authors describe complete remission of recurrent postprandial discomfort, nausea,
      and vomiting within 1 week of starting mirtazapine in a gastroparetic patient who
      had failed to respond, in 7 months, to conventional prokinetics (erythromycin,
      metoclopramide, domperidone, perphenazine, itopride, bethanechol, and/or
      tegaserod) and pyloric injection of botulinum toxin. This is the first report to
      show that mirtazapine may be an effective alternative when gastroparesis is
      refractory to conventional measures.

PMID- 16959935
TI  - Involuntary hospitalization of medical patients who lack decisional capacity: an
      unresolved issue.

PMID- 16959936
TI  - What is the psychiatrist to do with positive pregnancy tests in postmenopausal
      women?

PMID- 16959937
TI  - All-trans retinoic acid (ATRA) syndrome can mimic panic disorder.

PMID- 16959938
TI  - Catatonia after liver transplantation.

PMID- 16959939
TI  - Reformulating factitious disorder.

PMID- 16959941
TI  - cAMP inhibits transforming growth factor-beta-stimulated collagen synthesis via
      inhibition of extracellular signal-regulated kinase 1/2 and Smad signaling in
      cardiac fibroblasts.
AB  - Cardiac fibroblasts produce and degrade extracellular matrix and are critical in
      regulating cardiac remodeling and hypertrophy. Cytokines such as transforming
      growth factor-beta (TGF-beta) play a fundamental role in the development of
      tissue fibrosis by stimulating matrix deposition and other profibrotic responses,
      but less is known about pathways that might inhibit fibrosis. Increased cAMP
      formation inhibits myofibroblast differentiation and collagen production by
      cardiac fibroblasts, but the mechanism of this inhibition is not known. We sought
      to characterize the signaling pathways by which cAMP-elevating agents alter
      collagen expression and myofibroblast differentiation. Treatment with 10 microM
      forskolin or isoproterenol increased cAMP production and cAMP response element
      binding protein (CREB) phosphorylation in cardiac fibroblasts and inhibited serum
      or TGF-beta-stimulated collagen synthesis by 37% or more. These same cAMP
      elevating agents blunted TGF-beta-stimulated expression of collagen I, collagen
      III, and alpha-smooth muscle actin. Forskolin or isoproterenol treatment blocked
      the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) induced by
      TGF-beta despite the fact that these cAMP-elevating agents stimulated ERK1/2
      activation on their own. cAMP-elevating agents also attenuated the activation of
      c-Jun NH(2)-terminal kinase and reduced binding of the transcriptional
      coactivator CREB-binding protein 1 to transcriptional complexes containing Smad2,
      Smad3, and Smad4. Pharmacological inhibition of ERK completely blocked TGF-beta
      stimulated collagen gene expression, but expression of an active mutant of MEK
      was additive with TGF-beta treatment. Thus, cAMP-elevating agents inhibit the
      profibrotic effects of TGF-beta in cardiac fibroblasts largely through inhibiting
      ERK1/2 phosphorylation but also by reducing Smad-mediated recruitment of
      transcriptional coactivators.

PMID- 16959942
TI  - [D-Trp8]-gamma-melanocyte-stimulating hormone exhibits anti-inflammatory efficacy
      in mice bearing a nonfunctional MC1R (recessive yellow e/e mouse).
AB  - Two melanocortin receptors (MC1 and MC3R) have been identified as main
      transducers of the anti-inflammatory effects of natural and synthetic
      melanocortins. In this study, we have taken advantage of the recent description
      of the selective MC3R agonist [d-Trp(8)]-gamma-melanocyte-stimulating hormone
      (MSH) and of the recessive yellow (e/e) mouse, bearing a nonfunctional MC1R,
      thereby incrementing our knowledge on this topic. Culturing peritoneal
      macrophages of recessive yellow (e/e) mice with [d-Trp(8)]-gamma-MSH led to
      accumulation of cAMP, indicating MC3R receptor functionality: this effect was
      blocked by a neutralizing antibody against MC3R. Likewise, release of the
      chemokine KC by urate crystals was attenuated by [d-Trp(8)]-gamma-MSH, and this
      effect was prevented by synthetic [Ac-Nle(4)-c[Asp(5)-2'-Nal(7),Lys(10)]alpha
      MSH(4-10)-NH(2) (SHU9119)] and natural [agouti-related protein (AGRP)] MC3R
      antagonists but not by the MC4R antagonist Ac-Cys-Nle-Arg-His-d-2-Nal-Arg-Trp-Cys
      NH(2) (HS024). Systemic treatment of mice with [d-Trp(8)]-gamma-MSH inhibited KC
      release and polymorphonuclear cell accumulation elicited by urate crystals in the
      murine peritoneal cavity. SHU9119 and AGRP prevented the inhibitory actions of [d
      Trp(8)]-gamma-MSH, whereas HS024 was inactive. We also demonstrate here that [d
      Trp(8)]-gamma-MSH displays a dual mechanism of action by inducing the anti
      inflammatory protein heme-oxygenase 1 (HO-1). Treatment with the HO-1 inhibitor
      zinc protoporphyrin IX exacerbated the inflammatory response elicited by urate
      crystals and abrogated the anti-inflammatory effects of [d-Trp(8)]-gamma-MSH. In
      conclusion, these data support the development of the selective MC3R agonist [d
      Trp(8)]-gamma-MSH for the treatment of inflammatory pathologies, based on a dual
      mechanism of cytokine/chemokine inhibition and induction of the anti-inflammatory
      protein HO-1.

PMID- 16959943
TI  - Determinants of 1-piperidinecarboxamide, N-[2-[[5-amino-l-[[4-(4-pyridinyl)-l
      piperazinyl]carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2
      oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl) (BIBN4096BS) affinity for
      calcitonin gene-related peptide and amylin receptors--the role of receptor
      activity modifying protein 1.
AB  - 1-Piperidinecarboxamide, N-[2-[[5-amino-l-[[4-(4-pyridinyl)-l
      piperazinyl]carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2
      oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl) (BIBN4096BS), a calcitonin
      gene-related peptide (CGRP) receptor antagonist, can alleviate the symptoms of
      migraine and is highly selective for CGRP over adrenomedullin (AM) receptors.
      These receptors are heterodimers of the calcitonin receptor-like receptor (CL)
      and receptor activity modifying proteins (RAMPs), with the pharmacological
      properties determined by the RAMP subunit. BIBN4096BS-sensitive CGRP(1) receptors
      are CL/RAMP1, whereas BIBN4096BS-insensitive AM receptors are CL/RAMP2 or
      CL/RAMP3 (AM(1) and AM(2), respectively), implicating RAMP1 in conferring BIB
      N4096BS sensitivity. Because calcitonin receptors [CT((a))] also interact with
      RAMP1 [AMY(1(a)) receptors], BIBN4096BS could also have affinity for these
      receptors. To test this, receptors were transfected into COS-7 cells and agonist
      stimulated cAMP levels measured in the presence and absence of antagonists. We
      found that AMY(1(a)) receptors were approximately 150-fold less sensitive to
      BIBN4096BS antagonism than CGRP(1) receptors. In contrast, AMY(3(a))
      [CT((a))/RAMP3] or AM(2) receptors were not sensitive to BIBN4096BS antagonism.
      We investigated Trp74 in RAMP1, a residue implicated in the species selectivity
      of BIBN4096BS. BIBN4096BS affinity was reduced at AMY(1(a)) and CGRP(1) receptors
      when this residue was mutated to lysine or alanine. The equivalent residue in
      RAMP3, Glu74, when mutated to tryptophan (E74W), induced BIBN4096BS sensitivity
      at AM(2) and AMY(3(a)) receptors. It is interesting that a selective reduction in
      AM potency was observed at E74W AM(2) receptors, implicating this residue in AM
      interactions with this receptor. These data support the importance of Trp74 in
      RAMP1 in the interaction of BIBN4096BS with CGRP(1) and AMY(1(a)) receptors and
      identified Glu74 in RAMP3 as the first amino acid in RAMP important for agonist
      interactions with calcitonin-family receptors.

PMID- 16959944
TI  - The important role of Bcrp (Abcg2) in the biliary excretion of sulfate and
      glucuronide metabolites of acetaminophen, 4-methylumbelliferone, and harmol in
      mice.
AB  - The role of Mrp2, Bcrp, and P-glycoprotein in the biliary excretion of
      acetaminophen sulfate (AS) and glucuronide (AG), 4-methylumbelliferyl sulfate
      (4MUS) and glucuronide (4MUG), and harmol sulfate (HS) and glucuronide (HG) was
      studied in Abcc2(-/-), Abcg2(-/-), and Abcb1a(-/-)/Abcb1b(-/-) mouse livers
      perfused with the respective parent compounds using a cassette dosing approach.
      Biliary clearance of the sulfate conjugates was significantly decreased in Bcrp
      deficient mouse livers, resulting in negligible biliary excretion of AS, 4MUS,
      and HS. It is noteworthy that the most profound decrease in the biliary clearance
      of the glucuronide conjugates was observed in Bcrp-deficient mouse livers,
      although the biliary clearance of 4MUG was also approximately 35% lower in Mrp2
      deficient mouse livers. As expected, biliary excretion of conjugates was not
      impaired in P-glycoprotein-deficient livers. An appreciable increase in perfusate
      recovery due to a shift in the directionality of metabolite excretion, from bile
      to perfusate, was noted in knockout mice only for conjugates whose biliary
      clearance constituted an appreciable (> or =37%) fraction of total hepatic
      excretory clearance (i.e., 4MUS, HG, and HS). Biliary clearance of AG, AS, and
      4MUG constituted a small fraction of total hepatic excretory clearance, so an
      appreciable increase in perfusate recovery of these metabolites was not observed
      in knockout mice despite markedly decreased biliary excretion. Unlike in rats,
      where sulfate and glucuronide conjugates were excreted into bile predominantly by
      Mrp2, mouse Bcrp mediated the biliary excretion of sulfate metabolites and also
      played a major role in the biliary excretion of the glucuronide metabolites, with
      some minor contribution from mouse Mrp2.

PMID- 16959945
TI  - Structural requirements of transmembrane domain 3 for activation by the M1
      muscarinic receptor agonists AC-42, AC-260584, clozapine, and N
      desmethylclozapine: evidence for three distinct modes of receptor activation.
AB  - Transmembrane domain 3 (TM3) plays a crucial role mediating muscarinic
      acetylcholine receptor activation by acetylcholine, carbachol, and other
      muscarinic agonists. We compared the effects of point mutations throughout TM3 on
      the interactions of carbachol, 4-n-butyl-1-[4-(2-methylphenyl)-4-oxo-1-butyl]
      piperidine hydrogen chloride (AC-42), a potent structural analog of AC-42 called
      4-[3-(4-butylpiperidin-1-yl)-propyl]-7-fluoro-4H-benzo[1,4]oxazin-3-one (AC
      260584), N-desmethylclozapine, and clozapine with the M(1) muscarinic receptor.
      The binding and activation profiles of these ligands fell into three distinct
      patterns; one exemplified by orthosteric compounds like carbachol, another by
      structural analogs of AC-42, and a third by structural analogs of N
      desmethylclozapine. All mutations tested severely reduced carbachol binding and
      activation of M(1). In contrast, the agonist actions of AC-42 and AC-260584 were
      greatly potentiated by the W101A mutation, slightly reduced by Y106A, and
      slightly increased by S109A. Clozapine and N-desmethylclozapine displayed
      substantially increased maximum responses at the Y106A and W101A mutants,
      slightly lower activity at S109A, but no substantial changes in potency. At L102A
      and N110A, agonist responses to AC-42, AC-260584, clozapine, and N
      desmethylclozapine were all substantially reduced, but usually less than
      carbachol. D105A showed no functional responses to all ligands. Displacement and
      dissociation rate experiments demonstrated clear allosteric properties of AC-42
      and AC-260584 but not for N-desmethylclozapine and clozapine, indicating that
      they may contact different residues than carbachol to activate M(1) but occupy
      substantially overlapping spaces, in contrast to AC-42 and AC-260584, which
      occupy separable spaces. These results show that M(1) receptors can be activated
      in at least three distinct ways and that there is no requirement for potent
      muscarinic agonists to mimic acetylcholine interactions with TM3.

PMID- 16959946
TI  - IL-18 mediates the formation of stress-induced, histamine-dependent gastric
      lesions.
AB  - A role of IL-18 in the induction of gastric lesions by water immersion and
      restraint stress (WRS) was investigated. When wild-type BALB/c mice were exposed
      to WRS, levels of IL-18 in the serum and stomach increased rapidly with the
      development of acute gastric lesions. In IL-18-deficient mice [IL-18 knockout
      (KO) mice] similarly exposed to WRS, no gastric lesions were observed, but the
      administration of IL-18 before exposure to WRS resulted in the induction of WRS
      induced gastric lesions. WRS enhanced gastric histidine decarboxylase (HDC)
      activity with concomitant increases in gastric histamine content. In IL-18 KO
      mice, the WRS-induced elevation of gastric HDC activity and histamine levels was
      much less than that in wild-type mice, but it was augmented by prior
      administration of IL-18. Treatment of wild-type mice with cimetidine, a histamine
      H2 receptor antagonist, inhibited the formation of WRS-induced gastric lesions
      with no effect on the induction of gastric IL-18 by WRS. Levels of
      corticosterone, one of the stress indicators, were lower in IL-18 KO mice than in
      wild-type mice. The glucocorticoid receptor antagonist mifepristone had no effect
      on gastric IL-18 and histamine levels but aggravated the stress-induced gastric
      lesions, indicating that corticosterone was not involved in the IL-18-mediated
      formation of stress-induced gastric lesions. These results indicate that IL-18 is
      involved in the induction of gastric lesions by WRS through augmentation of HDC
      activity and production of histamine in the stomach.

PMID- 16959947
TI  - Molecular mechanisms involved in the adaptive regulation of human intestinal
      biotin uptake: A study of the hSMVT system.
AB  - Biotin, a water-soluble micronutrient, is vital for cellular functions, including
      growth and development. The human intestine utilizes the human sodium-dependent
      multivitamin transporter (hSMVT) for biotin uptake. Evidence exists showing that
      the intestinal biotin uptake process is adaptively regulated during biotin
      deficiency. Nothing, however, is known about molecular mechanism(s) involved
      during this adaptive regulation. This study compared two human-derived intestinal
      epithelial cell lines (HuTu-80 and Caco-2) during biotin-deficient or biotin
      sufficient states and with an approach that assessed carrier-mediated biotin
      uptake, hSMVT protein and RNA levels, RNA stability, and hSMVT promoter activity.
      The results showed that during biotin deficiency, a significant and specific
      upregulation in carrier-mediated biotin uptake occurred in both human intestinal
      epithelial cell lines and that this increase was associated with an induction in
      protein and mRNA levels of hSMVT. The increase in mRNA levels was not due to an
      increase in RNA stability but was associated with an increase in activity of the
      hSMVT promoter in transfected human intestinal cells. Using promoter deletion
      constructs and mutational analysis in transiently transfected HuTu-80 and Caco-2
      cells, a biotin deficiency-responsive region was mapped to a 103-bp area within
      the hSMVT promoter that contains gut-enriched Kruppel-like factor (GKLF) sites
      that confer the response to biotin deficiency. These results confirm that human
      intestinal biotin uptake is adaptively regulated and provide novel evidence
      demonstrating that the upregulation is not mediated via changes in hSMVT RNA
      stability but rather is due to transcriptional regulatory mechanism(s) that
      likely involve GKLF sites in the hSMVT promoter.

PMID- 16959948
TI  - Clinical phenotype and gene expression profile in Crohn's disease.
AB  - The clinical course varies significantly among patients with Crohn's disease
      (CD). This study investigated whether gene expression profiles generated by DNA
      microarray technology might predict disease progression. Biopsies from the
      descending colon were obtained colonoscopically from 40 CD patients. Gene
      profiling analyses were performed using a Human Genome U133 Plus 2.0 GeneChip
      Array, and summarization into a single expression measure for each probe set was
      performed using the robust multiple array procedure. Principal component analysis
      demonstrated that three components explain two-thirds of the total variation. The
      most important parameters for the determination of the colonic gene expression
      patterns were the presence of disease (CD) and presence of inflammation.
      Superimposition of clinical phenotype data revealed a grouping of the samples
      from patients with stenosis toward negative values on the axis of the second
      principal component. The functional annotation analysis suggested that the
      expression of genes involved in intracellular transport and cytoskeletal
      organization might influence the development of stenosis. In conclusion, even
      though most variation in the colonic gene expression patterns is due to presence
      or absence of CD and inflammation status, the development of stenosis is a
      parameter that affects colonic gene expression to some extent.

PMID- 16959949
TI  - Lymphocyte-mediated regulation of beta-endorphin in the myenteric plexus.
AB  - Lymphocytes are antinociceptive and can modulate visceral pain perception in
      mice. Previously, we have shown that adoptive transfer of CD4+ T cells to severe
      combined immune-deficient (SCID) mice normalized immunodeficiency-related
      visceral hyperalgesia. Pain attenuation was associated with an increase in beta
      endorphin release by T cells and an upregulation of beta-endorphin in the enteric
      nervous system. In this study, we investigated the relationship between T cells
      and opioid expression in the myenteric plexus. We examined opioid peptide and
      receptor expression in the myenteric plexus in the presence and absence of
      mucosal T cells. We found a positive association between T cells and beta
      endorphin expression; this was accompanied by a downregulation of the micro
      opioid receptor (MOR). In vitro, T helper (Th) type 1 and type 2 cytokine
      stimulation of CD4+ T cells or isolation of T cells from in vivo Th-polarized
      mice did not increase T cell release of beta-endorphin or the induction of beta
      endorphin expression in the myenteric plexus. However, exogenous beta-endorphin
      did upregulate beta-endorphin expression, and both cycloheximide and naloxone
      methiodide inhibited peptide upregulation. Therefore, our results suggest that
      nonpolarized CD4+ T cells release beta-endorphin, which, through an interaction
      with MOR, stimulates an upregulation of beta-endorphin expression in the
      myenteric plexus. Thus, we propose that the mechanism underlying lymphocyte
      modulation of visceral pain involves T cell modulation of opioid expression in
      the enteric nervous system.

PMID- 16959950
TI  - Liver cytokine production and ICAM-1 expression following bone fracture, tissue
      trauma, and hemorrhage in middle-aged mice.
AB  - Although studies have indicated that hemorrhagic shock and resuscitation produces
      hepatic damage by mechanisms involving adhesion molecules in endothelial cells
      and hepatocytes, it is not known if there is any difference in the extent of
      hepatic damage following bone fracture, soft tissue trauma, and hemorrhage (Fx
      TH) between young and middle-aged animals. To study this, young (6-8 wk) and
      middle-aged (approximately 12 mo) C3H/HeN male mice were subjected to a right
      lower leg fracture, soft tissue trauma, (i.e., midline laparotomy), and
      hemorrhage (blood withdrawal to decrease the blood pressure to 35 +/- 5 mmHg for
      90 min) followed by resuscitation with four times the shed blood volume in the
      form of lactated Ringer solution. Mice were euthanized 24 h later, and liver
      tissues were harvested. Total bilirubin levels in the hepatocyte extract
      increased markedly following Fx-TH in both groups of mice; however, the increase
      in middle-aged mice was significantly higher compared with young mice. TNF-alpha
      and IL-6 levels in the hepatocyte extract following Fx-TH increased significantly
      in middle-aged mice but remained unchanged in young mice. IL-10 levels
      significantly decreased in middle-aged mice following Fx-TH but remained
      unchanged in young mice. Kupffer cells from middle-aged mice produced
      significantly higher IL-6 and IL-10 levels compared with young mice. Protein
      levels and mRNA expression of ICAM-1 in hepatocytes were also significantly
      higher in middle-aged mice compared with young mice following Fx-TH. These
      results collectively suggest that the extent of hepatic damage following Fx-TH is
      dependent on the age of the subject.

PMID- 16959951
TI  - Na-K-ATPase regulates tight junction permeability through occludin
      phosphorylation in pancreatic epithelial cells.
AB  - Tight junctions are crucial for maintaining the polarity and vectorial transport
      functions of epithelial cells. We and others have shown that Na-K-ATPase plays a
      key role in the organization and permeability of tight junctions in mammalian
      cells and analogous septate junctions in Drosophila. However, the mechanism by
      which Na-K-ATPase modulates tight junctions is not known. In this study, using a
      well-differentiated human pancreatic epithelial cell line HPAF-II, we demonstrate
      that Na-K-ATPase is present at the apical junctions and forms a complex with
      protein phosphatase-2A, a protein known to be present at tight junctions.
      Inhibition of Na-K-ATPase ion transport function reduced protein phosphatase-2A
      activity, hyperphosphorylated occludin, induced rearrangement of tight junction
      strands, and increased permeability of tight junctions to ionic and nonionic
      solutes. These data suggest that Na-K-ATPase is required for controlling the
      tight junction gate function.

PMID- 16959952
TI  - Disruption of transforming growth factor-beta signaling by curcumin induces gene
      expression of peroxisome proliferator-activated receptor-gamma in rat hepatic
      stellate cells.
AB  - Activation of hepatic stellate cells (HSC), the major effectors of hepatic
      fibrogenesis, is coupled with sequential alterations in gene expression,
      including an increase in receptors for transforming growth factor-beta (TGF-beta)
      and a dramatic reduction in the peroxisome proliferator-activated receptor-gamma
      (PPAR-gamma). The relationship between them remains obscure. We previously
      demonstrated that curcumin induced gene expression of PPAR-gamma in activated
      HSC, leading to reducing cell proliferation, inducing apoptosis and suppressing
      expression of extracellular matrix genes. The underlying molecular mechanisms are
      largely unknown. We recently observed that stimulation of PPAR-gamma activation
      suppressed gene expression of TGF-beta receptors in activated HSC, leading to the
      interruption of TGF-beta signaling. This observation supported our assumption of
      an antagonistic relationship between PPAR-gamma activation and TGF-beta signaling
      in HSC. In this study, we further hypothesize that TGF-beta signaling might
      negatively regulate gene expression of PPAR-gamma in activated HSC. The present
      report demonstrates that exogenous TGF-beta1 inhibits gene expression of PPAR
      gamma in activated HSC, which is eliminated by the pretreatment with curcumin
      likely by interrupting TGF-beta signaling. Transfection assays further indicate
      that blocking TGF-beta signaling by dominant negative type II TGF-beta receptor
      increases the promoter activity of PPAR-gamma gene. Promoter deletion assays,
      site-directed mutageneses, and gel shift assays localize two Smad binding
      elements (SBEs) in the PPAR-gamma gene promoter, acting as curcumin response
      elements and negatively regulating the promoter activity in passaged HSC. The
      Smad3/4 protein complex specifically binds to the SBEs. Overexpression of Smad4
      dose dependently eliminates the inhibitory effects of curcumin on the PPAR-gamma
      gene promoter and TGF-beta signaling. Taken together, these results demonstrate
      that the interruption of TGF-beta signaling by curcumin induces gene expression
      of PPAR-gamma in activated HSC in vitro. Our studies provide novel insights into
      the molecular mechanisms of curcumin in the induction of PPAR-gamma gene
      expression and in the inhibition of HSC activation.

PMID- 16959953
TI  - Differentiation of the gastric mucosa. I. Role of histamine in control of
      function and integrity of oxyntic mucosa: understanding gastric physiology
      through disruption of targeted genes.
AB  - Many physiological functions of the stomach depend on an intact mucosal
      integrity; function reflects structure and vice versa. Histamine in the stomach
      is synthesized by histidine decarboxylase (HDC), stored in enterochromaffin-like
      (ECL) cells, and released in response to gastrin, acting on CCK(2) receptors on
      the ECL cells. Mobilized ECL cell histamine stimulates histamine H(2) receptors
      on the parietal cells, resulting in acid secretion. The parietal cells express
      H(2), M(3), and CCK(2) receptors and somatostatin sst(2) receptors. This review
      discusses the consequences of disrupting genes that are important for ECL cell
      histamine release and synthesis (HDC, gastrin, and CCK(2) receptor genes) and
      genes that are important for "cross-talk" between H(2) receptors and other
      receptors on the parietal cell (CCK(2), M(3), and sst(2) receptors). Such
      analysis may provide insight into the functional significance of gastric
      histamine.

PMID- 16959955
TI  - A new model of chronic pancreatitis in rats.
AB  - This study was designed to examine whether continuous pancreatic ductal
      hypertension (PDH) plays an important role in the onset and development of
      chronic pancreatitis (CP). Pancreatic, biliary, and duodenal cannulas were
      implanted in male Wistar rats. PDH was induced by vertically raising the free end
      of the pancreatic duct cannula to exert a hydrostatic pressure and maintained for
      2 wk. PDH was gradually increased, but when the pancreatic juice (PJ) flow was
      interrupted, PDH was decreased to restore PJ flow. The induction of PDH resulted
      in a marked reduction of amylase activity in PJ and an increase in serum amylase
      activity. At 2 wk after persistent PDH, pancreatic exocrine function was markedly
      decreased in response to a bolus injection of secretin (100 pmol/kg) compared
      with the control group. Histological examination revealed interlobular as well as
      intralobular fibrosis in the form of nodular pancreatitis at 2 wk after the
      induction of PDH. Immunohistochemistry revealed the expression of fibronectin and
      collagen types I and III. Quantitative real-time RT-PCR showed an increase in
      transforming growth factor-beta(1) mRNA expression in the pancreas during PDH.
      The present results suggest that PDH plays an important role in the onset and
      development of CP. Furthermore, our animal model seems useful for investigating
      the mechanisms of CP in rats.

PMID- 16959954
TI  - LPS inhibits fasted plasma ghrelin levels in rats: role of IL-1 and PGs and
      functional implications.
AB  - LPS injected intraperitoneally decreases fasted plasma levels of ghrelin at 3 h
      postinjection in rats. We characterized the inhibitory action of LPS on plasma
      ghrelin and whether exogenous ghrelin restores LPS-induced suppression of food
      intake and gastric emptying in fasted rats. Plasma ghrelin and insulin and blood
      glucose were measured after intraperitoneal injection of LPS, intravenous
      injection of IL-1beta and urocortin 1, and in response to LPS under conditions of
      blockade of IL-1 or CRF receptors by subcutaneous injection of IL-1 receptor
      antagonist (IL-1Ra) or astressin B, respectively, and prostaglandin (PG)
      synthesis by intraperitoneal indomethacin. Food intake and gastric emptying were
      measured after intravenous injection of ghrelin at 5 h postintraperitoneal LPS
      injection. LPS inhibited the elevated fasted plasma ghrelin levels by 47.6 +/-
      4.9%, 58.9 +/- 3.3%, 74.4 +/- 2.7%, and 48.9 +/- 8.7% at 2, 3, 5, and 7 h
      postinjection, respectively, and values returned to preinjection levels at 24 h.
      Insulin levels were negatively correlated to those of ghrelin, whereas there was
      no significant correlation between glucose and ghrelin. IL-1Ra and indomethacin
      prevented the first 3-h decline in ghrelin levels induced by LPS, whereas
      astressin B did not. IL-1beta inhibited plasma ghrelin levels, whereas urocortin
      1 had no influence. Ghrelin injected intravenously prevented an LPS-induced 87%
      reduction of gastric emptying and 61% reduction of food intake. These data showed
      that IL-1 and PG pathways are part of the early mechanisms by which LPS
      suppresses fasted plasma ghrelin and that exogenous ghrelin can normalize LPS
      induced-altered digestive functions.

PMID- 16959956
TI  - Molecular cloning and functional expression of a VIP-specific receptor.
AB  - Three receptors for VIP and pituitary adenylate cyclase-activating peptide
      (PACAP) have been cloned and characterized: PAC(1), with high affinity for PACAP,
      and VPAC(1) and VPAC(2) with equally high affinity for VIP and PACAP. The
      existence of a VIP-specific receptor (VIP(s)) in guinea pig (GP) teniae coli
      smooth muscle was previously surmised on the basis of functional studies, and its
      existence was confirmed by cloning of a partial NH(2)-terminal sequence. Here we
      report the cloning of the full-length cDNAs of two receptors, a VPAC(2) receptor
      from GP gastric smooth muscle and VIP(s) from GP teniae coli smooth muscle. The
      cDNA sequence of the VIP(s) encodes a 437-amino acid protein (M(r) 49,560) that
      possesses 87% similarity to VPAC(2) receptors in rat and mouse and differs from
      the VPAC(2) receptor in GP gastric smooth muscle by only two amino-acid residues,
      F(40)F(41) in lieu of L(40)L(41). In COS-1 cells transfected with the GP teniae
      coli smooth muscle receptor, only VIP bound with high affinity (IC(50) 1.4 nM)
      and stimulated cAMP formation with high potency (EC(50) 1 nM). In contrast, in
      COS-1 cells transfected with the GP gastric smooth muscle receptor, both VIP and
      PACAP bound with equally high affinity (IC(50) 2.3 nM) and stimulated cAMP with
      equally high potency (EC(50) 1.5 nM). We conclude that the receptor cloned from
      GP teniae coli smooth muscle is a VIP(s) distinct from VPAC(1) and VPAC(2)
      receptors. The ligand specificity in this species is determined by a pair of
      adjacent phenylalanine residues (L(40)L(41)) in the NH(2)-terminal ligand-binding
      domain.

PMID- 16959957
TI  - Increased expression of midkine in the rat colon during healing of experimental
      colitis.
AB  - Midkine (MK) is a unique growth and differentiation factor that modulates the
      proliferation and migration of various cells; however, little is known regarding
      its relationship to intestinal diseases. The aim of this study was to investigate
      MK expression and its role in dextran sulfate sodium (DSS)-induced colitis in
      rats. The expressions of MK, receptor-like protein-tyrosine phosphatase (RPTP)
      beta, and proinflammatory cytokines were examined in rat colonic tissues after
      the development of DSS-induced colitis using Northern blotting,
      immunohistochemistry, and laser-capture microdissection (LCM) coupled with RT
      PCR. The effects of MK on the migration of intestinal epithelial cells (IEC-6)
      were also evaluated in vitro using an intestinal wound repair model. MK
      expression was significantly increased in damaged colonic mucosa, mainly from day
      3 to day 5 after the end of DSS administration, with abundant MK immunoreactive
      signals detected in submucosal fibroblasts. Expressions of proinflammatory
      cytokines were most strongly induced on day 1, which preceded the augmentation of
      MK expression. Results of LCM coupled with RT-PCR clearly indicated RPTP-beta
      expression in colonic epithelial cells. The migration assay showed that wound
      repair in the MK-treated groups was accelerated dose dependently. The present
      results showed for the first time that intestinal inflammation upregulates the MK
      RPTP-beta system, which may stimulate mucosal regeneration during the process of
      healing of colitis. Additional investigations regarding the role of MK may
      contribute to the development of new options for the treatment of inflammatory
      bowel diseases.

PMID- 16959959
TI  - In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates, the selective 5
      hydroxytryptamine 1a agonist (R)-(+)-8-OHDPAT inhibits levodopa-induced
      dyskinesia but only with? increased motor disability.
AB  - 5-Hydroxytryptamine 1a (5-HT(1a)) receptor agonists, such as sarizotan and
      tandospirone, are reported to reduce levodopa-induced dyskinesia in 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaques and in Parkinson's
      disease without worsening motor disability. However, these compounds are not
      specific for 5-HT(1a) receptors and also possess dopamine antagonist actions. We
      now report on the effects of (2R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin [(R)
      (+)-8-OHDPAT], a selective 5-HT(1a) agonist lacking dopaminergic activity, on
      motor disability and dyskinesia (chorea and dystonia) in levodopa-primed MPTP
      treated common marmosets. Administration of (R)-(+)-8-OHDPAT (0.2, 0.6, and 2.0
      mg/kg s.c), in conjunction with levodopa/carbidopa (12.5 mg/kg each p.o.) to
      levodopa-primed animals, dose-dependently reduced levodopa-induced chorea but did
      not affect dystonic movements. However, (R)-(+)-8-OHDPAT treatment also reduced
      locomotor activity and the reversal of motor disability. Administration of (R)
      (+)-8-OHDPAT alone had no effects of motor behaviors. The effects of (R)-(+)-8
      OHDPAT on levodopa-induced motor behaviors were antagonized by the 5-HT(1a)
      receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2
      pyridinylcyclohexanecarboxamide maleate (WAY-100635) (1.0 mg/kg s.c.).
      Administration of (R)-(+)-8-OHDPAT (0.6 mg/kg s.c.) also reduced chorea produced
      by the administration of the D(2)/D(3) dopamine receptor agonist pramipexole
      (0.06 mg/kg p.o.) to levodopa-primed MPTP-treated animals. However, again the
      increase in locomotor activity and reversal of motor disability produced by
      pramipexole were also inhibited. These data suggest that selective 5-HT(1a)
      agonists do not provide an effective means of suppressing levodopa-induced
      dyskinesia, except with worsening of parkinsonism.

PMID- 16959960
TI  - Coadministration of sorafenib with rottlerin potently inhibits cell proliferation
      and migration in human malignant glioma cells.
AB  - Mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) are activated
      in the majority of gliomas and contribute to tumor cell growth and survival.
      Sorafenib (Bay43-9006; Nexavar) is a dual-action Raf and vascular endothelial
      growth factor receptor inhibitor that blocks receptor phosphorylation and MAPK
      mediated signaling and inhibits growth in a number of tumor types. Because our
      initial studies of this agent in a series of glioma cell lines showed only
      partial growth inhibition at clinically achievable concentrations, we questioned
      whether inhibition of PKC signaling using the PKC-delta inhibitor rottlerin might
      potentiate therapeutic efficacy. Proliferation assays, apoptosis induction
      studies, and Western immunoblot analysis were conducted in cells treated with
      sorafenib and rottlerin as single agents or in combination. Sorafenib and
      rottlerin reduced proliferation in all cell lines when used as single agents, and
      the combination produced marked potentiation of growth inhibition. Flow
      cytometric measurements of cells stained with Annexin V-propidium iodide and
      immunocytochemical assessment of cytochrome c and apoptosis-inducing factor
      release demonstrated that addition of rottlerin resulted in significantly higher
      levels of apoptosis than sorafenib alone. In addition, the combination of
      sorafenib and rottlerin reduced or completely inhibited the phosphorylation of
      extracellular signal-regulated kinase and Akt and down-regulated cell cycle
      regulatory proteins such as cyclin-D1, cyclin-D3, cyclin-dependent kinase (cdk)4,
      and cdk6 in a dose- and time-dependent manner. Our results clearly indicate that
      inhibition of PKC-delta signaling enhances the antiproliferative effect of
      sorafenib in malignant human glioma cell lines and support the examination of
      combinations of signaling inhibitors in these tumors.

PMID- 16959961
TI  - Up-regulation of heme oxygenase provides vascular protection in an animal model
      of diabetes through its antioxidant and antiapoptotic effects.
AB  - Heme oxygenase (HO) plays a critical role in the regulation of cellular oxidative
      stress. The effects of the reactive oxygen species scavenger ebselen and the HO
      inducers cobalt protoporphyrin and stannous chloride (SnCl(2)) on HO protein
      levels and activity, indices of oxidative stress, and the progression of diabetes
      were examined in the Zucker rat model of type 2 diabetes. The onset of diabetes
      coincided with an increase in HO-1 protein levels and a paradoxical decrease in
      HO activity, which was restored by administration of ebselen. Up-regulation of HO
      1 expressed in the early development of diabetes produced a decrease in
      oxidative/nitrosative stress as manifested by decreased levels of 3
      nitrotyrosine, superoxide, and cellular heme content. This was accompanied by a
      decrease in endothelial cell sloughing and reduced blood pressure. Increased HO
      activity was also associated with a significant increase in the antiapoptotic
      signaling molecules Bcl-xl and phosphorylation of p38-mitogen-activated protein
      kinase but no significant increases in Bcl-2 or BAD proteins. In conclusion, 3
      nitrotyrosine, cellular heme, and superoxide, promoters of vascular damage, are
      reduced by HO-1 induction, thereby preserving vascular integrity and protecting
      cardiac function involving an increase in antiapoptotic proteins.

PMID- 16959962
TI  - A fungal family of transcriptional regulators: the zinc cluster proteins.
AB  - The trace element zinc is required for proper functioning of a large number of
      proteins, including various enzymes. However, most zinc-containing proteins are
      transcription factors capable of binding DNA and are named zinc finger proteins.
      They form one of the largest families of transcriptional regulators and are
      categorized into various classes according to zinc-binding motifs. This review
      focuses on one class of zinc finger proteins called zinc cluster (or binuclear)
      proteins. Members of this family are exclusively fungal and possess the well
      conserved motif CysX(2)CysX(6)CysX(5-12)CysX(2)CysX(6-8)Cys. The cysteine
      residues bind to two zinc atoms, which coordinate folding of the domain involved
      in DNA recognition. The first- and best-studied zinc cluster protein is Gal4p, a
      transcriptional activator of genes involved in the catabolism of galactose in the
      budding yeast Saccharomyces cerevisiae. Since the discovery of Gal4p, many other
      zinc cluster proteins have been characterized; they function in a wide range of
      processes, including primary and secondary metabolism and meiosis. Other roles
      include regulation of genes involved in the stress response as well as
      pleiotropic drug resistance, as demonstrated in budding yeast and in human fungal
      pathogens. With the number of characterized zinc cluster proteins growing
      rapidly, it is becoming more and more apparent that they are important regulators
      of fungal physiology.

PMID- 16959964
TI  - The Yin and Yang of P-TEFb regulation: implications for human immunodeficiency
      virus gene expression and global control of cell growth and differentiation.
AB  - The positive transcription elongation factor b (P-TEFb) stimulates
      transcriptional elongation by phosphorylating the carboxy-terminal domain of RNA
      polymerase II and antagonizing the effects of negative elongation factors. Not
      only is P-TEFb essential for transcription of the vast majority of cellular
      genes, but it is also a critical host cellular cofactor for the expression of the
      human immunodeficiency virus (HIV) type 1 genome. Given its important role in
      globally affecting transcription, P-TEFb's activity is dynamically controlled by
      both positive and negative regulators in order to achieve a functional
      equilibrium in sync with the overall transcriptional demand as well as the
      proliferative state of cells. Notably, this equilibrium can be shifted toward
      either the active or inactive state in response to diverse physiological stimuli
      that can ultimately affect the cellular decision between growth and
      differentiation. In this review, we examine the mechanisms by which the recently
      identified positive (the bromodomain protein Brd4) and negative (the noncoding
      7SK small nuclear RNA and the HEXIM1 protein) regulators of P-TEFb affect the P
      TEFb-dependent transcriptional elongation. We also discuss the consequences of
      perturbations of the dynamic associations of these regulators with P-TEFb in
      relation to the pathogenesis and progression of several major human diseases,
      such as cardiac hypertrophy, breast cancer, and HIV infection.

PMID- 16959966
TI  - Genetics of Streptomyces rimosus, the oxytetracycline producer.
AB  - From a genetic standpoint, Streptomyces rimosus is arguably the best
      characterized industrial streptomycete as the producer of oxytetracycline and
      other tetracycline antibiotics. Although resistance to these antibiotics has
      reduced their clinical use in recent years, tetracyclines have an increasing role
      in the treatment of emerging infections and noninfective diseases. Procedures for
      in vivo and in vitro genetic manipulations in S. rimosus have been developed
      since the 1950s and applied to study the genetic instability of S. rimosus
      strains and for the molecular cloning and characterization of genes involved in
      oxytetracycline biosynthesis. Recent advances in the methodology of genome
      sequencing bring the realistic prospect of obtaining the genome sequence of S.
      rimosus in the near term.

PMID- 16959963
TI  - The yeast actin cytoskeleton: from cellular function to biochemical mechanism.
AB  - All cells undergo rapid remodeling of their actin networks to regulate such
      critical processes as endocytosis, cytokinesis, cell polarity, and cell
      morphogenesis. These events are driven by the coordinated activities of a set of
      20 to 30 highly conserved actin-associated proteins, in addition to many cell
      specific actin-associated proteins and numerous upstream signaling molecules. The
      combined activities of these factors control with exquisite precision the spatial
      and temporal assembly of actin structures and ensure dynamic turnover of actin
      structures such that cells can rapidly alter their cytoskeletons in response to
      internal and external cues. One of the most exciting principles to emerge from
      the last decade of research on actin is that the assembly of architecturally
      diverse actin structures is governed by highly conserved machinery and
      mechanisms. With this realization, it has become apparent that pioneering efforts
      in budding yeast have contributed substantially to defining the universal
      mechanisms regulating actin dynamics in eukaryotes. In this review, we first
      describe the filamentous actin structures found in Saccharomyces cerevisiae
      (patches, cables, and rings) and their physiological functions, and then we
      discuss in detail the specific roles of actin-associated proteins and their
      biochemical mechanisms of action.

PMID- 16959967
TI  - The bacterial cytoskeleton.
AB  - In recent years it has been shown that bacteria contain a number of cytoskeletal
      structures. The bacterial cytoplasmic elements include homologs of the three
      major types of eukaryotic cytoskeletal proteins (actin, tubulin, and intermediate
      filament proteins) and a fourth group, the MinD-ParA group, that appears to be
      unique to bacteria. The cytoskeletal structures play important roles in cell
      division, cell polarity, cell shape regulation, plasmid partition, and other
      functions. The proteins self-assemble into filamentous structures in vitro and
      form intracellular ordered structures in vivo. In addition, there are a number of
      filamentous bacterial elements that may turn out to be cytoskeletal in nature.
      This review attempts to summarize and integrate the in vivo and in vitro aspects
      of these systems and to evaluate the probable future directions of this active
      research field.

PMID- 16959965
TI  - The selective value of bacterial shape.
AB  - Why do bacteria have shape? Is morphology valuable or just a trivial secondary
      characteristic? Why should bacteria have one shape instead of another? Three
      broad considerations suggest that bacterial shapes are not accidental but are
      biologically important: cells adopt uniform morphologies from among a wide
      variety of possibilities, some cells modify their shape as conditions demand, and
      morphology can be tracked through evolutionary lineages. All of these imply that
      shape is a selectable feature that aids survival. The aim of this review is to
      spell out the physical, environmental, and biological forces that favor different
      bacterial morphologies and which, therefore, contribute to natural selection.
      Specifically, cell shape is driven by eight general considerations: nutrient
      access, cell division and segregation, attachment to surfaces, passive dispersal,
      active motility, polar differentiation, the need to escape predators, and the
      advantages of cellular differentiation. Bacteria respond to these forces by
      performing a type of calculus, integrating over a number of environmental and
      behavioral factors to produce a size and shape that are optimal for the
      circumstances in which they live. Just as we are beginning to answer how bacteria
      create their shapes, it seems reasonable and essential that we expand our efforts
      to understand why they do so.

PMID- 16959968
TI  - Mapping the pathways to staphylococcal pathogenesis by comparative secretomics.
AB  - The gram-positive bacterium Staphylococcus aureus is a frequent component of the
      human microbial flora that can turn into a dangerous pathogen. As such, this
      organism is capable of infecting almost every tissue and organ system in the
      human body. It does so by actively exporting a variety of virulence factors to
      the cell surface and extracellular milieu. Upon reaching their respective
      destinations, these virulence factors have pivotal roles in the colonization and
      subversion of the human host. It is therefore of major importance to obtain a
      clear understanding of the protein transport pathways that are active in S.
      aureus. The present review aims to provide a state-of-the-art roadmap of
      staphylococcal secretomes, which include both protein transport pathways and the
      extracytoplasmic proteins of these organisms. Specifically, an overview is
      presented of the exported virulence factors, pathways for protein transport,
      signals for cellular protein retention or secretion, and the exoproteomes of
      different S. aureus isolates. The focus is on S. aureus, but comparisons with
      Staphylococcus epidermidis and other gram-positive bacteria, such as Bacillus
      subtilis, are included where appropriate. Importantly, the results of genomic and
      proteomic studies on S. aureus secretomes are integrated through a comparative
      "secretomics" approach, resulting in the first definition of the core and variant
      secretomes of this bacterium. While the core secretome seems to be largely
      employed for general housekeeping functions which are necessary to thrive in
      particular niches provided by the human host, the variant secretome seems to
      contain the "gadgets" that S. aureus needs to conquer these well-protected
      niches.

PMID- 16959971
TI  - Characterization of cellular retinoid-binding proteins in human myometrium during
      pregnancy.
AB  - Many complementary or competing signalling pathways bear an influence on the
      myometrium at any one time, and because the retinoic acid signalling pathway
      influences differentiation of a wide array of human tissues, this may be one of
      the determinants of myometrial differentiation during pregnancy. We have explored
      the novel hypothesis that the retinoids may act as important regulators in
      controlling the differentiated state of the human myometrium during pregnancy by
      characterizing the expression profiles for cellular retinoid-binding proteins
      CRBPI, CRABPI and CRABPII in non-pregnant, pregnant (non-labouring) and labouring
      human myometrium taken from the functionally distinct upper and lower uterine
      segments. In addition, we have investigated the effect of all-trans retinoic acid
      (ATRA) on the expression of several retinoic acid response genes including
      cyclooxygenase-2 (COX-2) and connexin-43 (Cx-43). Different spatial and temporal
      patterns of expression were observed for CRBPI, CRABPI and CRABPII within the
      upper and lower uterine segments through the three trimesters of pregnancy and in
      labour. Furthermore, the expression of COX-2, Cx-43, CRABPI, the transcription
      factor c-Jun and the retinoic acid receptor RARbeta altered in response to
      different concentrations of ATRA, suggesting that the differential expression of
      cellular retinoid-binding proteins may lead to different levels of retinoic acid
      being delivered to its nuclear targets, leading to the differential expression of
      specific target genes within the myometrium during pregnancy.

PMID- 16959970
TI  - Epigenetic gene regulation in the bacterial world.
AB  - Like many eukaryotes, bacteria make widespread use of postreplicative DNA
      methylation for the epigenetic control of DNA-protein interactions. Unlike
      eukaryotes, however, bacteria use DNA adenine methylation (rather than DNA
      cytosine methylation) as an epigenetic signal. DNA adenine methylation plays
      roles in the virulence of diverse pathogens of humans and livestock animals,
      including pathogenic Escherichia coli, Salmonella, Vibrio, Yersinia, Haemophilus,
      and Brucella. In Alphaproteobacteria, methylation of adenine at GANTC sites by
      the CcrM methylase regulates the cell cycle and couples gene transcription to DNA
      replication. In Gammaproteobacteria, adenine methylation at GATC sites by the Dam
      methylase provides signals for DNA replication, chromosome segregation, mismatch
      repair, packaging of bacteriophage genomes, transposase activity, and regulation
      of gene expression. Transcriptional repression by Dam methylation appears to be
      more common than transcriptional activation. Certain promoters are active only
      during the hemimethylation interval that follows DNA replication; repression is
      restored when the newly synthesized DNA strand is methylated. In the E. coli
      genome, however, methylation of specific GATC sites can be blocked by cognate DNA
      binding proteins. Blockage of GATC methylation beyond cell division permits
      transmission of DNA methylation patterns to daughter cells and can give rise to
      distinct epigenetic states, each propagated by a positive feedback loop.
      Switching between alternative DNA methylation patterns can split clonal bacterial
      populations into epigenetic lineages in a manner reminiscent of eukaryotic cell
      differentiation. Inheritance of self-propagating DNA methylation patterns governs
      phase variation in the E. coli pap operon, the agn43 gene, and other loci
      encoding virulence-related cell surface functions.

PMID- 16959972
TI  - An essential role for LEDGF/p75 in HIV integration.
AB  - Chromosomal integration enables human immunodeficiency virus (HIV) to establish a
      permanent reservoir that can be therapeutically suppressed but not eradicated.
      Participation of cellular proteins in this obligate replication step is poorly
      understood. We used intensified RNA interference and dominant-negative protein
      approaches to show that the cellular transcriptional coactivator lens epithelium
      derived growth factor (LEDGF)/p75 (p75) is an essential HIV integration cofactor.
      The mechanism requires both linkages of a molecular tether that p75 forms between
      integrase and chromatin. Fractionally minute levels of endogenous p75 are
      sufficient to enable integration, showing that cellular factors that engage HIV
      after entry may elude identification in less intensive knockdowns. Perturbing the
      p75-integrase interaction may have therapeutic potential.

PMID- 16959969
TI  - Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and
      where are we going?
AB  - Since poly-ADP ribose was discovered over 40 years ago, there has been
      significant progress in research into the biology of mono- and poly-ADP
      ribosylation reactions. During the last decade, it became clear that ADP
      ribosylation reactions play important roles in a wide range of physiological and
      pathophysiological processes, including inter- and intracellular signaling,
      transcriptional regulation, DNA repair pathways and maintenance of genomic
      stability, telomere dynamics, cell differentiation and proliferation, and
      necrosis and apoptosis. ADP-ribosylation reactions are phylogenetically ancient
      and can be classified into four major groups: mono-ADP-ribosylation, poly-ADP
      ribosylation, ADP-ribose cyclization, and formation of O-acetyl-ADP-ribose. In
      the human genome, more than 30 different genes coding for enzymes associated with
      distinct ADP-ribosylation activities have been identified. This review highlights
      the recent advances in the rapidly growing field of nuclear mono-ADP-ribosylation
      and poly-ADP-ribosylation reactions and the distinct ADP-ribosylating enzyme
      families involved in these processes, including the proposed family of novel poly
      ADP-ribose polymerase-like mono-ADP-ribose transferases and the potential mono
      ADP-ribosylation activities of the sirtuin family of NAD(+)-dependent histone
      deacetylases. A special focus is placed on the known roles of distinct mono- and
      poly-ADP-ribosylation reactions in physiological processes, such as mitosis,
      cellular differentiation and proliferation, telomere dynamics, and aging, as well
      as "programmed necrosis" (i.e., high-mobility-group protein B1 release) and
      apoptosis (i.e., apoptosis-inducing factor shuttling). The proposed molecular
      mechanisms involved in these processes, such as signaling, chromatin modification
      (i.e., "histone code"), and remodeling of chromatin structure (i.e., DNA damage
      response, transcriptional regulation, and insulator function), are described. A
      potential cross talk between nuclear ADP-ribosylation processes and other NAD(+)
      dependent pathways is discussed.

PMID- 16959973
TI  - Structure of the 70S ribosome complexed with mRNA and tRNA.
AB  - The crystal structure of the bacterial 70S ribosome refined to 2.8 angstrom
      resolution reveals atomic details of its interactions with messenger RNA (mRNA)
      and transfer RNA (tRNA). A metal ion stabilizes a kink in the mRNA that
      demarcates the boundary between A and P sites, which is potentially important to
      prevent slippage of mRNA. Metal ions also stabilize the intersubunit interface.
      The interactions of E-site tRNA with the 50S subunit have both similarities and
      differences compared to those in the archaeal ribosome. The structure also
      rationalizes much biochemical and genetic data on translation.

PMID- 16959974
TI  - The consensus coding sequences of human breast and colorectal cancers.
AB  - The elucidation of the human genome sequence has made it possible to identify
      genetic alterations in cancers in unprecedented detail. To begin a systematic
      analysis of such alterations, we determined the sequence of well-annotated human
      protein-coding genes in two common tumor types. Analysis of 13,023 genes in 11
      breast and 11 colorectal cancers revealed that individual tumors accumulate an
      average of approximately 90 mutant genes but that only a subset of these
      contribute to the neoplastic process. Using stringent criteria to delineate this
      subset, we identified 189 genes (average of 11 per tumor) that were mutated at
      significant frequency. The vast majority of these genes were not known to be
      genetically altered in tumors and are predicted to affect a wide range of
      cellular functions, including transcription, adhesion, and invasion. These data
      define the genetic landscape of two human cancer types, provide new targets for
      diagnostic and therapeutic intervention, and open fertile avenues for basic
      research in tumor biology.

PMID- 16959975
TI  - Unraveling the mystery of Indian monsoon failure during El Nino .
AB  - The 132-year historical rainfall record reveals that severe droughts in India
      have always been accompanied by El Nino events. Yet El Nino events have not
      always produced severe droughts. We show that El Nino events with the warmest sea
      surface temperature (SST) anomalies in the central equatorial Pacific are more
      effective in focusing drought-producing subsidence over India than events with
      the warmest SSTs in the eastern equatorial Pacific. The physical basis for such
      different impacts is established using atmospheric general circulation model
      experiments forced with idealized tropical Pacific warmings. These findings have
      important implications for Indian monsoon forecasting.

PMID- 16959976
TI  - Offshore aquaculture legislation.

PMID- 16959978
TI  - European science. Basic science agency gets a tag-team leadership.

PMID- 16959977
TI  - Cancer. First pass at cancer genome reveals complex landscape.

PMID- 16959979
TI  - FDA. Proposed guidelines for emergency research aim to quell confusion.

PMID- 16959980
TI  - Stem cell research. Scientists object to Massachusetts rules.

PMID- 16959982
TI  - University funding. Academic earmarks: the money schools love to hate.

PMID- 16959981
TI  - Science funding. Germany launches a high-tech initiative.

PMID- 16959983
TI  - Climate science. U.S. Supreme Court gets arguments for EPA to regulate CO2.

PMID- 16959985
TI  - Ecology. A threatened nature reserve breaks down Asian borders.

PMID- 16959984
TI  - Neuroscience. A better view of brain disorders.

PMID- 16959986
TI  - Evolutionary ecology. Sex and the single killifish.

PMID- 16959987
TI  - Bioengineering. Artificial arrays could help submarines make like a fish.

PMID- 16959988
TI  - Climate science. Sea animals get tagged for double-duty research.

PMID- 16959989
TI  - Declines in funding of NIH R01 research grants.

PMID- 16959990
TI  - IRBs: going too far or not far enough?

PMID- 16959991
TI  - Comment on "Transitions to asexuality result in excess amino acid substitutions".
AB  - Paland and Lynch (Reports, 17 February 2006, p. 990) showed that in Daphnia
      pulex, the ratio of amino acid replacement to silent substitution in
      mitochondrial genes is higher in asexual lineages than in sexual lineages. If
      this base-composition bias is maintained by selection, it too should alter
      following transitions in reproductive mode. Analysis reveals no such change in
      the genomes of D. pulex.

PMID- 16959992
TI  - Epidemiology. Infectious diseases: preparing for the future.

PMID- 16959993
TI  - Psychology. Is she conscious?

PMID- 16959994
TI  - Ecology. How does climate change affect biodiversity?

PMID- 16959996
TI  - Applied physics. Waves on the horizon.

PMID- 16959995
TI  - Cell biology. Peptides, scrambled and stitched.

PMID- 16959997
TI  - Physics. Entangled solid-state circuits.

PMID- 16959998
TI  - Detecting awareness in the vegetative state.
AB  - We used functional magnetic resonance imaging to demonstrate preserved conscious
      awareness in a patient fulfilling the criteria for a diagnosis of vegetative
      state. When asked to imagine playing tennis or moving around her home, the
      patient activated predicted cortical areas in a manner indistinguishable from
      that of healthy volunteers.

PMID- 16959999
TI  - Two years at Meridiani Planum: results from the Opportunity Rover.
AB  - The Mars Exploration Rover Opportunity has spent more than 2 years exploring
      Meridiani Planum, traveling approximately 8 kilometers and detecting features
      that reveal ancient environmental conditions. These include well-developed
      festoon (trough) cross-lamination formed in flowing liquid water, strata with
      smaller and more abundant hematite-rich concretions than those seen previously,
      possible relict "hopper crystals" that might reflect the formation of halite,
      thick weathering rinds on rock surfaces, resistant fracture fills, and networks
      of polygonal fractures likely caused by dehydration of sulfate salts. Chemical
      variations with depth show that the siliciclastic fraction of outcrop rock has
      undergone substantial chemical alteration from a precursor basaltic composition.
      Observations from microscopic to orbital scales indicate that ancient Meridiani
      once had abundant acidic groundwater, arid and oxidizing surface conditions, and
      occasional liquid flow on the surface.

PMID- 16960000
TI  - Exotic Earths: forming habitable worlds with giant planet migration.
AB  - Close-in giant planets (e.g., "hot Jupiters") are thought to form far from their
      host stars and migrate inward, through the terrestrial planet zone, via torques
      with a massive gaseous disk. Here we simulate terrestrial planet growth during
      and after giant planet migration. Several-Earth-mass planets also form interior
      to the migrating jovian planet, analogous to recently discovered "hot Earths."
      Very-water-rich, Earth-mass planets form from surviving material outside the
      giant planet's orbit, often in the habitable zone and with low orbital
      eccentricities. More than a third of the known systems of giant planets may
      harbor Earth-like planets.

PMID- 16960001
TI  - Observation of electroluminescence and photovoltaic response in ionic junctions.
AB  - Electronic devices primarily use electronic rather than ionic charge carriers.
      Using soft-contact lamination, we fabricated ionic junctions between two organic
      semiconductors with mobile anions and cations, respectively. Mobile ionic charge
      was successfully deployed to control the direction of electronic current flow in
      semiconductor devices. As a result, these devices showed electroluminescence
      under forward bias and a photovoltage upon illumination with visible light. Thus,
      ionic charge carriers can enhance the performance of existing electronic devices,
      as well as enable new functionalities.

PMID- 16960002
TI  - Tectonic uplift and Eastern Africa aridification.
AB  - The history of Eastern African hominids has been linked to a progressive increase
      of open grassland during the past 8 million years. This trend was explained by
      global climatic processes, which do not account for the massive uplift of eastern
      African topography that occurred during this period. Atmosphere and biosphere
      simulations quantify the role played by these tectonic events. The reduced
      topographic barrier before 8 million years ago permitted a zonal circulation with
      associated moisture transport and strong precipitation. Our results suggest that
      the uplift itself led to a drastic reorganization of atmospheric circulation,
      engendering the strong aridification and paleoenvironmental changes suggested by
      the data.

PMID- 16960003
TI  - Measurement of the entanglement of two superconducting qubits via state
      tomography.
AB  - Demonstration of quantum entanglement, a key resource in quantum computation
      arising from a nonclassical correlation of states, requires complete measurement
      of all states in varying bases. By using simultaneous measurement and state
      tomography, we demonstrated entanglement between two solid-state qubits. Single
      qubit operations and capacitive coupling between two super-conducting phase
      qubits were used to generate a Bell-type state. Full two-qubit tomography yielded
      a density matrix showing an entangled state with fidelity up to 87%. Our results
      demonstrate a high degree of unitary control of the system, indicating that
      larger implementations are within reach.

PMID- 16960004
TI  - Cold-seep mollusks are older than the general marine mollusk fauna.
AB  - The origin and possible antiquity of faunas at deep-sea hydrothermal vents and
      seeps have been debated since their discovery. We used the fossil record of seep
      mollusks to show that the living seep genera have significantly longer geologic
      ranges than the marine mollusks in general, but have ranges similar to those of
      deep-sea taxa, suggesting that seep faunas may be shaped by the factors that
      drive the evolution of life in the deep sea in general. Our data indicate that
      deep-sea anoxic/dysoxic events did not affect seep faunas, casting doubt on the
      suggested anoxic nature and/or global extent of these events.

PMID- 16960005
TI  - Temporal and spatial enumeration processes in the primate parietal cortex.
AB  - Humans and animals can nonverbally enumerate visual items across time in a
      sequence or rapidly estimate the set size of spatial dot patterns at a single
      glance. We found that temporal and spatial enumeration processes engaged
      different populations of neurons in the intraparietal sulcus of behaving monkeys.
      Once the enumeration process was completed, however, another neuronal population
      represented the cardinality of a set irrespective of whether it had been cued in
      a spatial layout or across time. These data suggest distinct neural processing
      stages for different numerical formats, but also a final convergence of the
      segregated information to form most abstract quantity representations.

PMID- 16960006
TI  - Isolated chloroplast division machinery can actively constrict after stretching.
AB  - Chloroplast division involves plastid-dividing, dynamin, and FtsZ (PDF) rings. We
      isolated intact supertwisted (or spiral) and circular PDF machineries from
      chloroplasts of the red alga Cyanidioschyzon merolae. After individual intact PDF
      machineries were stretched to four times their original lengths with optical
      tweezers, they spontaneously returned to their original sizes. Dynamin-released
      PDF machineries did not retain the spiral structure and could not be stretched.
      Thus, dynamin may generate the motive force for contraction by filament sliding
      in dividing chloroplasts, in addition to pinching-off the membranes.

PMID- 16960007
TI  - Humanization of yeast to produce complex terminally sialylated glycoproteins.
AB  - Yeast is a widely used recombinant protein expression system. We expanded its
      utility by engineering the yeast Pichia pastoris to secrete human glycoproteins
      with fully complex terminally sialylated N-glycans. After the knockout of four
      genes to eliminate yeast-specific glycosylation, we introduced 14 heterologous
      genes, allowing us to replicate the sequential steps of human glycosylation. The
      reported cell lines produce complex glycoproteins with greater than 90% terminal
      sialylation. Finally, to demonstrate the utility of these yeast strains,
      functional recombinant erythropoietin was produced.

PMID- 16960008
TI  - An antigen produced by splicing of noncontiguous peptides in the reverse order.
AB  - CD8-positive T lymphocytes recognize peptides that are usually derived from the
      degradation of cellular proteins and are presented by class I molecules of the
      major histocompatibility complex. Here we describe a human minor
      histocompatibility antigen created by a polymorphism in the SP110 nuclear
      phosphoprotein gene. The antigenic peptide comprises two noncontiguous SP110
      peptide segments spliced together in reverse order to that in which they occur in
      the predicted SP110 protein. The antigenic peptide could be produced in vitro by
      incubation of precursor peptides with highly purified 20S proteasomes. Cutting
      and splicing probably occur within the proteasome by transpeptidation.

PMID- 16960009
TI  - Gene transposition as a cause of hybrid sterility in Drosophila.
AB  - We describe reproductive isolation caused by a gene transposition. In certain
      Drosophila melanogaster-D. simulans hybrids, hybrid male sterility is caused by
      the lack of a single-copy gene essential for male fertility, JYAlpha. This gene
      is located on the fourth chromosome of D. melanogaster but on the third
      chromosome of D. simulans. Genomic and molecular analyses show that JYAlpha
      transposed to the third chromosome during the evolutionary history of the D.
      simulans lineage. Because of this transposition, a fraction of hybrids completely
      lack JYAlpha and are sterile, representing reproductive isolation without
      sequence evolution.

PMID- 16960010
TI  - Washing away your sins: threatened morality and physical cleansing.
AB  - Physical cleansing has been a focal element in religious ceremonies for thousands
      of years. The prevalence of this practice suggests a psychological association
      between bodily purity and moral purity. In three studies, we explored what we
      call the "Macbeth effect"-that is, a threat to one's moral purity induces the
      need to cleanse oneself. This effect revealed itself through an increased mental
      accessibility of cleansing-related concepts, a greater desire for cleansing
      products, and a greater likelihood of taking antiseptic wipes. Furthermore, we
      showed that physical cleansing alleviates the upsetting consequences of unethical
      behavior and reduces threats to one's moral self-image. Daily hygiene routines
      such as washing hands, as simple and benign as they might seem, can deliver a
      powerful antidote to threatened morality, enabling people to truly wash away
      their sins.

PMID- 16960011
TI  - Personal finance. Young scientists need firm plan to make up for a late start.
AB  - After what may seem like endless on-the-job training, scientists need to move
      quickly to map out a sound, long-term financial strategy.

PMID- 16960012
TI  - Personal finance. Summer salary and other windfalls.
AB  - How to spend windfalls such as the "summer salary" of an academic scientist is an
      important part of your overall financial planning strategy.

PMID- 16960013
TI  - Personal finance. Making the most of a good thing.
AB  - Science Careers offers a financial-planning case study of a typical academic
      family.

PMID- 16960014
TI  - Personal finance. So what should you invest in?
AB  - You don't need to become an investment guru to learn what you need to know.

PMID- 16960015
TI  - Current value of preimplantation genetic aneuploidy screening in IVF.
AB  - Preimplantation genetic aneuploidy screening (PGS) has been performed during the
      last decade as a way of enhancing embryo selection in patients with an increased
      incidence of embryonic numerical chromosome abnormalities (advanced maternal age,
      recurrent miscarriage and recurrent implantation failure). It has been proposed
      that the replacement of euploid embryos in these patients would result in a
      higher implantation and pregnancy rate and a reduced miscarriage rate.
      Additionally, the transfer of fewer embryos could reduce the chances for multiple
      pregnancies in all IVF patients. Although, to date, multiple studies have
      addressed this issue, contradictory results have been encountered. As a result,
      the effectiveness of aneuploidy screening remains to be established. Moreover,
      child outcome studies documenting the safety of this procedure are needed. The
      aim of this review is to summarize the available evidence concerning the use of
      PGS to determine the current value of the technique.

PMID- 16960016
TI  - Wide genomic analysis of human endometrial receptivity: new times, new
      opportunities.
AB  - Microarray technology has broadened the insight into many research fields
      allowing scientists to analyse the expression of many genes in quick and
      efficient experiments aimed at translating these findings into clinical
      applications. In reproductive medicine, researchers have exploited microarrays to
      increase understanding of the molecular mechanisms involved in endometrial
      receptivity and how a possible therapeutic translation can be feasible. In the
      last 4 years, several studies have focused on the genomics of the human
      endometrium in different physiological and pathological conditions, and these
      studies have generated a large amount of information about the regulation and
      dysregulation of the window of implantation (WOI) genes in fertile, subfertile
      and refractory conditions. However, the key molecules/mechanisms in endometrial
      receptivity remain to be elucidated. In this comprehensive review, we have
      analysed the available results obtained in our own and other laboratories,
      defining the genomic profile of the receptive endometrium in different situations
      and its possible clinical application.

PMID- 16960017
TI  - Uterine stem cells: what is the evidence?
AB  - The mucosal lining (endometrium) of the human uterus undergoes cyclical processes
      of regeneration, differentiation and shedding as part of the menstrual cycle.
      Endometrial regeneration also follows parturition, almost complete resection and
      in post-menopausal women taking estrogen replacement therapy. In non-menstruating
      species, there are cycles of endometrial growth and apoptosis rather than
      physical shedding. The concept that endometrial stem/progenitor cells are
      responsible for the remarkable regenerative capacity of endometrium was proposed
      many years ago. However, attempts to isolate, characterize and locate endometrial
      stem cells have only been undertaken in the last few years as experimental
      approaches to identify adult stem/progenitor cells in other tissues have been
      developed. Adult stem cells are defined by their functional properties rather
      than by marker expression. Evidence for the existence of adult stem/progenitor
      cells in human and mouse endometrium is now emerging because functional stem cell
      assays are being applied to uterine cells and tissues. These fundamental studies
      on endometrial stem/progenitor cells will provide new insights into the
      pathophysiology of various gynaecological disorders associated with abnormal
      endometrial proliferation, including endometrial cancer, endometrial hyperplasia,
      endometriosis and adenomyosis.

PMID- 16960018
TI  - Expression profiling identifies three pathways altered in cellular
      immortalization: interferon, cell cycle, and cytoskeleton.
AB  - Abrogation of cellular senescence, resulting in immortalization, is a necessary
      step in the tumorigenic transformation of a cell. Four independent, spontaneously
      immortalized Li-Fraumeni syndrome (LFS) cell lines were used to analyze the gene
      expression changes that may have given these cell lines the growth advantage
      required to become immortal. A cellular senescence-like phenotype can be induced
      in immortal LFS cells by treating them with the DNA methyltransferase (DNMT)
      inhibitor 5-aza-deoxycytidine. We hypothesized, therefore, that genes
      epigenetically silenced by promoter methylation are potentially key regulators of
      senescence. We used microarrays to compare the epigenetic gene expression
      profiles of precrisis LFS cells with immortal LFS cells. Gene ontology analysis
      of the expression data revealed a statistically significant contribution of
      interferon pathway, cell cycle, and cytoskeletal genes in the process of
      immortalization. The identification of the genes and pathways regulating
      immortalization will lead to a better understanding of cellular immortalization
      and molecular targets in cancer and aging.

PMID- 16960019
TI  - Effect of leptin on hypothalamic gene expression in calorie-restricted rats.
AB  - Diminished leptin signaling to the arcuate nucleus of hypothalamus (ARH) may
      induce calorie restriction (CR)-specific neuroendocrine and metabolic adaptation,
      which is potentially relevant to the effect of CR. The present study investigated
      whether restoration of leptin signaling to the ARH could reverse CR-induced
      alterations in neuropeptide gene expression in rats. Male F344 rats, fed ad
      libitum or a 30% CR diet from 6 weeks of age, received leptin or vehicle
      intracerebroventricularly for 14 days via osmotic mini-pumps implanted in the
      subcutis at 34 weeks of age. The messenger RNA levels were quantified by real
      time reverse transcription-polymerase chain reaction using total RNA extracted
      from microdissected tissues containing the ARH. The results indicated that leptin
      administration reversed the upregulated expression of neuropeptide Y and agouti
      related protein genes in CR rats, suggesting the possibility of a role for the
      leptin-ARH pathway in the effect of CR.

PMID- 16960020
TI  - Effect of age on vascular beta2-adrenergic receptor desensitization is not
      mediated by the receptor coupling to Galphai proteins.
AB  - Beta-adrenergic receptor (beta-AR)-mediated vasorelaxation declines with age. In
      the vasculature, beta2-AR undergoes protein kinase A-mediated desensitization
      that causes a switch in the G protein coupled to beta2-AR; Galphai links instead
      of Galphas. We exposed Fischer 344 rat aortae of increasing age to a
      desensitizing dose of isoproterenol, and determined its effect on beta2-AR
      mediated vasorelaxation. Desensitization decreased beta2-AR-mediated
      vasorelaxation in young aortae only. Subsequently, we used pertussis toxin to
      block Galphai to determine whether changes in beta2-AR/G protein coupling
      occurred. Galphai inhibition did not reverse desensitization or the age-related
      change, but there appears to be a population of beta2-AR linked to Galphai, as
      pertussis toxin treatment improved beta2-AR-mediated vasorelaxation in aortae
      from animals of all ages. These findings suggest aortic beta2-AR in older animals
      may be maximally desensitized, which would explain impaired vasorelaxation. Our
      results also imply that protein kinase A-mediated beta2-AR desensitization may
      not be responsible for the age-related decline.

PMID- 16960021
TI  - Whole blood analysis of phagocytosis, apoptosis, cytokine production, and
      leukocyte subsets in healthy older men and women: the ZENITH study.
AB  - Few studies to date have examined age-related changes in markers of immune status
      in healthy older individuals. The immune status of 93 healthy individuals aged 55
      70 years was assessed by two- and three-color flow cytometry and biochemical
      analysis. There were significant age effects (p <or=.05) on monocyte phagocytic
      activity and cluster of differentiation (CD) 3/human leukocyte antigen-D-related
      (HLA-DR) late-activated T lymphocytes (% expression). There was a significant (p
      <or= 0.1) Age x Sex interaction in absolute counts (x 10(9)/L) of CD3/CD8 total
      cytotoxic T lymphocytes (CTL), the CD4 T- helper to CD8 CTL ratio, the
      CD3/CD4/CD45RA naive T helper to CD3/CD4/CD45RO memory T helper lymphocyte ratio,
      and interleukin (IL)-1beta (% expression) by activated monocytes. The study shows
      that alterations in markers of immune status occur between 55 and 70 years, and
      provides reference values for the lymphocyte measures in healthy men and
      postmenopausal women in this age group. The study further highlights the need for
      sex-specific reference ranges for such markers.

PMID- 16960022
TI  - Sex differences in the association of apolipoprotein E and angiotensin-converting
      enzyme gene polymorphisms with healthy aging and longevity: a population-based
      study from Southern Italy.
AB  - We investigated the association of sex and age with the occurrence of
      apolipoprotein E (apoE) and angiotensin-converting enzyme (ACE) genotypes in
      healthy aging and longevity in 1344 healthy individuals and 64 centenarians. As
      compared to participants younger than 60 years, a significant higher frequency of
      the apoE/epsilon2 was observed in men aged 60-90 years (p <.001) and in
      centenarians (p <.001). Logistic regression analysis confirmed this outcome in
      both participants aged 60-90 years (odds ratio [OR] = 1.897; 95% confidence
      interval [CI], 1.227-2.931) and centenarians (OR = 3.263; 95% CI, 1.860-5.722). A
      further significant association of ACE/D allele and age was observed in
      centenarians (OR = 2.135; 95% CI, 1.253-3.636). Heterosis was also observed at
      the ACE locus. No relationship between apoE and ACE polymorphism was found. These
      findings suggest a role of sex in the association of apoE and ACE gene
      polymorphisms with healthy aging and longevity.

PMID- 16960023
TI  - Nutritional risk and low weight in community-living older adults: a review of the
      literature (1995-2005).
AB  - Although many studies have examined weight loss and low weight in
      institutionalized persons, there has been little research exploring the community
      living older adult's nutritional risk. The purpose of this literature review
      (1995-2005) is to describe our current understanding of nutritional risk and low
      weight in community-living older adults 65 years old and older. Computerized
      database searches and footnote reviews were used to find published studies on
      nutritional risk and low weight. Twenty-two research articles are reviewed and
      summarized. Each study was reviewed according to preset criteria.

PMID- 16960024
TI  - Effect of family-style meals on energy intake and risk of malnutrition in dutch
      nursing home residents: a randomized controlled trial.
AB  - BACKGROUND: Social facilitation and meal ambiance have beneficial effects on food
      intake in healthy adults. Extrapolation to the nursing home setting may lead to
      less malnutrition among the residents. Therefore, we investigate the effect of
      family-style meals on energy intake and the risk of malnutrition in Dutch nursing
      home residents. METHODS: In 2002 and 2003, a randomized controlled trial was
      conducted among 178 residents (mean age 77 years) in five Dutch nursing homes.
      Within each home, two wards were randomized into an intervention (n = 94) and a
      control group (n = 84). For 6 months, the intervention group received their meals
      family style, and the control group received the usual individual preplating
      services. Outcome measures were intakes of energy (kJ), carbohydrates (g), fat
      (g), and protein (g) and Mini Nutritional Assessment (MNA) score (0-30). RESULTS:
      The change in daily energy intake between the control and intervention group
      differed significantly (991 kJ; 95% confidence interval [CI], 504-1479). The
      difference in intake of macronutrients was 29.2 g (95% CI, 13.5-44.9) for
      carbohydrate, 9.1 g (95% CI, 2.9-15.2) for fat, and 8.6 g (95% CI, 3.4-13.6) for
      protein. The percentage of residents in the intervention group classified by the
      MNA as malnourished decreased from 17% to 4%, whereas this percentage increased
      from 11% to 23% in the control group. CONCLUSIONS: Family-style meals stimulate
      daily energy intake and protect nursing home residents against malnourishment.
      Therefore, replacement of the preplating meal services with family-style meals in
      nursing homes is recommended.

PMID- 16960025
TI  - One year of caloric restriction in humans: feasibility and effects on body
      composition and abdominal adipose tissue.
AB  - BACKGROUND: Caloric restriction (CR) increases maximal life span in short-lived
      organisms, and its effects are being explored in nonhuman primates. The
      objectives of this study were to determine the feasibility of prolonged CR in
      nonobese adults and to compare the effects of CR- and exercise-induced weight
      loss on body composition and abdominal adiposity. METHODS: A randomized,
      controlled trial was conducted with 48 healthy, nonobese women and men, aged 57
      +/- 1 (mean +/- standard error [SE]) years, with body mass index 27.3 +/- 0.3
      kg/m2. Participants were randomly assigned to a 20% calorically-restricted diet
      (CR, n = 19), exercise designed to produce a similar energy deficit (EX, n = 19),
      or a healthy lifestyle control group (HL, n = 10) for 1 year. Assessments
      included weight, body composition by dual-energy x-ray absorptiometry, abdominal
      adipose tissue by magnetic resonance imaging, and energy intake by doubly labeled
      water. RESULTS: The average level of CR achieved by the CR group was 11.5 +/-
      2.1%, and the EX group completed 59 +/- 6.7% of their prescribed exercise. Weight
      changes were greater (p <or=.0005) in the CR (-8.0 +/- 0.9 kg) and EX (-6.4 +/-
      0.9) groups as compared to the HL group (-1.3 +/- 0.9 kg), corresponding to
      reductions of 10.7%, 8.4%, and 1.7% of baseline weights, respectively. Whole-body
      fat mass and visceral and subcutaneous abdominal adipose tissue decreased
      significantly (p <.005) and comparably in the CR and EX groups, but did not
      change in the HL group. CONCLUSIONS: CR for 1 year was feasible, but the level of
      CR achieved was less than prescribed. CR and exercise were equally effective in
      reducing weight and adiposity.

PMID- 16960026
TI  - Dementia-free survival among centenarians: an evidence-based review.
AB  - BACKGROUND: The 2000 U.S. census identified 50,454 Americans older than 100 years
      (18 per 100,000). Increased longevity is only of benefit if accompanied by the
      maintenance of physical, social, and cognitive function into advanced age. The
      goal of this review was to identify research describing centenarians to find the
      prevalence of dementia-free survival. METHODS: We reviewed 650 publications to
      find studies that described the prevalence of dementia in centenarians, were
      community-based, had data that were specific to persons older than 100 years, and
      were published in peer-reviewed journals. For each study, we identified the
      prevalence of dementia, the completeness of the sample, the number of study
      participants, the method used to diagnose dementia, and the duration of the
      study. RESULTS: We identified 20 research groups from 14 countries with
      publications meeting our search criteria. The studies showed substantial
      variation in methods of assessing cognitive status, assuring a complete cohort,
      and sample size. Few studies reported longitudinal data or attempted diagnosis of
      the cause of dementia. The prevalence of dementia-free survival past 100 years of
      age varied between 0 and 50 percent. CONCLUSIONS: The methodology used in studies
      regarding dementia prevalence among centenarians is sufficiently varied that
      combination of existing studies into a meta-analysis is not possible. Suggestions
      for assuring quality in future centenarian research are presented.

PMID- 16960027
TI  - DHEAS levels and mortality in disabled older women: the Women's Health and Aging
      Study I.
AB  - BACKGROUND: Dehydroepiandrosterone sulfate (DHEAS) is an endogenously produced
      sex steroid that has been hypothesized to have anti-aging effects. Low DHEAS
      levels are associated with mortality in older men, but the relationship between
      DHEAS levels and mortality in women is not clearly defined. METHODS: The
      relationship between serum DHEAS level and 5-year mortality was analyzed in a
      cohort of 539 disabled women aged 65-100 years enrolled in the Women's Health and
      Aging Study I (WHAS I). Using Cox proportional hazard models, we calculated
      multivariate-adjusted mortality risks by DHEAS quartiles and by DHEAS
      continuously, allowing for a nonlinear relationship. We also examined cause
      specific mortality. RESULTS: We found a U-shaped relationship between DHEAS level
      and mortality. After adjusting for multiple covariates, women in the top and
      bottom DHEAS quartiles had a more than 2-fold higher 5-year mortality than did
      those in the middle quartiles (hazard ratio, 2.15; 95% confidence interval [CI],
      1.17-3.98 for the top quartile and 2.05; 95% CI, 1.27-3.32 for the bottom
      quartile, each compared to the third quartile). Women with higher DHEAS levels
      tended to have greater cancer mortality, whereas those with lower DHEAS tended to
      have greater cardiovascular mortality. CONCLUSION: Disabled older women with
      either low or high levels of DHEAS are at greater risk for death than are those
      with intermediate levels. More research is needed to determine if targeted
      dehydroepiandrosterone supplementation would provide clinical benefit to disabled
      older women.

PMID- 16960028
TI  - Effect of Alzheimer caregiving stress and age on frailty markers interleukin-6, C
      reactive protein, and D-dimer.
AB  - BACKGROUND: Elevated plasma levels of interleukin (IL)-6, C-reactive protein
      (CRP), and D-dimer belong to the biological alterations of the "frailty
      syndrome," defining increased vulnerability for diseases and mortality with
      aging. We hypothesized that, compatible with premature frailty, chronic stress
      and age are related in predicting inflammation and coagulation activity in
      Alzheimer caregivers. METHODS: Plasma IL-6, CRP, and D-dimer levels were measured
      in 170 individuals (mean age 73 +/- 9 years; 116 caregivers, 54 noncaregiving
      controls). Demographic factors, diseases, drugs, and lifestyle variables
      potentially affecting inflammation and coagulation were obtained by history and
      adjusted for as covariates in statistical analyses. RESULTS: Caregivers had
      higher mean levels of IL-6 (1.38 +/- 1.42 vs 1.00 +/- 0.92 pg/mL, p =.032) and of
      D-dimer (723 +/- 530 vs 471 +/- 211 ng/mL, p <.001) than controls had. CRP levels
      were similar between groups (p =.44). The relationship between caregiver status
      and D-dimer was independent of covariates (p =.037) but affected by role
      overload. Age accounted for much of the relationship with IL-6. After controlling
      for covariates, the interaction between caregiver status and age was significant
      for D-dimer (beta =.20, p =.029) and of borderline significance for IL-6 (beta
      =.17, p =.090). Post hoc regression analyses indicated that, among caregivers,
      age was significantly correlated with both D-dimer (beta =.50, p <.001) and IL-6
      (beta =.38, p =.001). Among controls, however, no significant relationship was
      observed between age and either D-dimer or IL-6. CONCLUSIONS: The interaction
      between caregiving status and age for D-dimer and IL-6 suggests the possibility
      that older caregivers could be at risk of a more rapid transition to the frailty
      syndrome and clinical manifestations of cardiovascular diseases.

PMID- 16960029
TI  - Informal caregiver involvement and illness detection among cognitively impaired
      nursing home residents.
AB  - BACKGROUND: The participation of informal caregivers in the care of nursing home
      (NH) residents has the potential to positively impact care, especially for
      cognitively impaired residents whose own ability to advocate for their care is
      often limited. This study examined relationships between the level of informal
      caregiver involvement (ICI) in the NH and the degree to which residents' common
      medical conditions were detected by facility staff. METHODS: One hundred pairs of
      cognitively impaired residents and their primary informal caregivers were
      enrolled from three facilities in the Baltimore, Maryland area. Data collection
      involved interviews with informal caregivers and facility staff, as well as a
      medical evaluation and chart review of residents. A measure of illness detection
      was created by comparing a medical examination of the resident with chart review
      information. ICI was measured via staff rating and informal caregiver self
      report. RESULTS: Correlations between illness detection and ICI were significant,
      with r = -.46 (p <.001) and r = -.39 (p <.001), for staff rating and self
      reports, respectively. In regression models taking into account resident
      characteristics (age, race, gender, comorbidities, payment status, duration of
      stay, and cognitive impairment) and facility differences, higher ICI and being
      female predicted higher rates of illness detection. CONCLUSIONS: Though the cross
      sectional nature of the study prevents the analysis of causal relationships, the
      involvement level of informal caregivers in the NH care of cognitively impaired
      residents was statistically related to higher rates of illness detection.
      Ramifications for the role of informal caregivers in long-term care are
      discussed.

PMID- 16960030
TI  - Does depression in older medical inpatients predict mortality?
AB  - BACKGROUND: Previous studies of the effect of depression on mortality among older
      medical inpatients have yielded inconsistent results. We examined the effects on
      mortality of both a diagnosis of depression at hospital admission and a history
      of previous depression, taking into account potential sources of bias (sample
      selection and confounding). METHODS: Medical inpatients aged 65+ with at most
      mild cognitive impairment were recruited at two Montreal hospitals and were
      screened for depression. All those with a diagnosis of major or minor depression
      (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV]
      criteria) and a random sample of nondepressed patients were invited to
      participate. Baseline data included: history of previous depression, severity of
      physical illness, comorbidity, and health services utilization. Cox proportional
      hazards methods were used to analyze survival during the 16- to 52-month follow
      up period. RESULTS: Five hundred patients were enrolled; 116 (23.2%) had a
      history of previous depression. After adjustment for demographic factors,
      physical illness, cognitive impairment, and prior service utilization, the only
      depression group with significantly different mortality was patients with both
      current major depression and a history of depression, who had lower mortality
      than all other patient groups (hazard ratio 0.42; 95% confidence interval: 0.25,
      0.70). CONCLUSIONS: Among patients with no history of depression, a diagnosis of
      depression was not associated with mortality after adjustment for confounding by
      physical illness and other factors. Coincident major depression and history of
      depression was associated with decreased mortality.

PMID- 16960032
TI  - The effects of anticholinergic insecticides on human mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) are located primarily in the bone marrow and are
      characterized by their capacity to differentiate into mesenchymal lineages such
      as bone, fat, and cartilage in response to appropriate signals. Several signaling
      mechanisms act to control MSC survival, proliferation, and differentiation, and
      failure or disruption of these signaling pathways can lead to degenerative
      disease or neoplasia. Organophosphate (OP) and carbamate pesticides, which are
      used in large amounts in agriculture to control insects, are designed to disrupt
      acetylcholine signaling by inhibiting the enzyme acetylcholinesterase (AChE).
      Effects of OP and carbamate pesticides on the human central nervous system have
      been well documented. However, AChE is broadly distributed, and the effects of
      anticholinergic insecticides on nonnervous tissue have received little attention.
      In the present study we found that human MSCs express AChE, which makes these
      cells potential targets for AChE inhibiting agents. We therefore examined the
      effects of an OP pesticide, chlorpyrifos, and a carbamate, carbofuran, on MSC
      characteristics. It was found that micromolar concentrations of these
      anticholinergic insecticides had no effect on MSC survival or proliferation but
      limited MSC differentiation capacity by inhibiting osteogenic differentiation.
      These results demonstrate that exposure to micromolar concentrations of OP and
      carbamate pesticides may affect tissue turnover and pathophysiology by
      interfering with MSC regulation.

PMID- 16960031
TI  - Differences in multiple segment tremor dynamics between young and elderly
      persons.
AB  - BACKGROUND: Physiological tremor is an intrinsic and highly variable motor output
      that is sensitive to alteration in both neuromuscular function and/or changing
      task demands. Given that any tremor increase can severely influence fine motor
      performance, there is a requirement to clarify what factors lead to increased
      tremor. Identification of those factors that alter tremor may be particularly
      pertinent for elderly persons, who often exhibit a decline in postural control
      and amplified tremor. The aim of this study was to examine the effect of whole
      body posture (seated vs standing) on multiple segment tremor and forearm
      electromyogram (EMG) activity of younger and older individuals. METHODS: Fourteen
      older and 12 young participants performed a bilateral pointing task. Tremor data
      were collected using accelerometers attached to the forearm, hand, and finger
      segments of each arm. Surface EMG data were also collected from the extensor
      digitorum muscle of each arm. RESULTS: Although the pattern of tremor was similar
      between age groups, older participants exhibited increased hand and finger tremor
      amplitude and increased EMG activity across all postural conditions. For older
      individuals, tremor increases were greatest when the participant performed the
      task in a standing position. All age-related increases in hand and/or finger
      tremor were confined to increases in peak power between 8 Hz and 12 Hz.
      CONCLUSIONS: From a clinical perspective, these findings illustrate that using
      multiple segment tremor analyses can provide additional insight into potential
      age-related tremor differences. Additionally, the fact that postural position had
      a pronounced effect on tremor in older individuals suggests that body posture
      should be considered as a potential confounding factor when assessing tremor
      differences between population groups.

PMID- 16960033
TI  - Ceramide synthase inhibition by fumonisin B1 treatment activates sphingolipid
      metabolizing systems in mouse liver.
AB  - Sphingolipids are important components of cell structure and cell signaling. Both
      external and internal stimuli can alter levels of cellular sphingolipids by
      regulating enzyme activities associated with sphingolipid metabolism. Fumonisin
      B1, mycotoxin produced by Fusarium verticillioides, is a reportedly specific
      inhibitor of ceramide synthase. In order to test our hypothesis whether ceramide
      synthase inhibition by fumonisin B1 alters other sphingolipid-metabolizing
      enzymes, we investigated the changes in free sphingoid bases and sphingomyelin
      (SM) and activities of key enzymes for their metabolism, sphingomyelinase
      (SMase), serine palmitoyltransferase (SPT), and sphingosine kinase (SPHK) in
      mouse liver. The hepatic free sphingoid bases increased significantly following
      five daily treatments with fumonisin B1 in mice. The activity of acidic SMase was
      enhanced by fumonisin B1, accompanied with a decrease in liver SM content. The
      expression and activities of SPT and SPHK1 in liver increased significantly
      following fumonisin B1 treatment. Another hepatotoxicant acetaminophen caused
      liver regeneration similar to fumonisin B1 but did not produce similar effects on
      liver sphingolipid-metabolizing enzymes, suggesting that activation of
      sphingolipid metabolism was not a consequence of hepatocyte regeneration. Data
      suggest that ceramide synthase inhibition by fumonisin B1 treatment stimulates
      sphingolipid-metabolizing systems to maintain a balance of cellular
      sphingolipids.

PMID- 16960034
TI  - Comparative toxicogenomic analysis of the hepatotoxic effects of TCDD in Sprague
      Dawley rats and C57BL/6 mice.
AB  - In an effort to further characterize conserved and species-specific mechanisms of
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated toxicity, comparative
      temporal and dose-response microarray analyses were performed on hepatic tissue
      from immature, ovariectomized Sprague Dawley rats and C57BL/6 mice. For temporal
      studies, rats and mice were gavaged with 10 or 30 microg/kg of TCDD,
      respectively, and sacrificed after 2, 4, 8, 12, 18, 24, 72, or 168 h while dose
      response studies were performed at 24 h. Hepatic gene expression profiles were
      monitored using custom cDNA microarrays containing 8567 (rat) or 13,361 (mouse)
      cDNA clones. Affymetrix data from male rats treated with 40 microg/kg TCDD were
      also included to expand the species comparison. In total, 3087 orthologous genes
      were represented in the cross-species comparison. Comparative analysis identified
      33 orthologous genes that were commonly regulated by TCDD as well as 185 rat
      specific and 225 mouse-specific responses. Functional annotation using Gene
      Ontology identified conserved gene responses associated with xenobiotic/chemical
      stress and amino acid and lipid metabolism. Rat-specific gene expression
      responses were associated with cellular growth and lipid metabolism while mouse
      specific responses were associated with lipid uptake/metabolism and immune
      responses. The common and species-specific gene expression responses were also
      consistent with complementary histopathology, clinical chemistry, hepatic lipid
      analyses, and reports in the literature. These data expand our understanding of
      TCDD-mediated gene expression responses and indicate that species-specific
      toxicity may be mediated by differences in gene expression which may help explain
      the wide range of species sensitivities and will have important implications in
      risk assessment strategies.

PMID- 16960035
TI  - Molecular biology for the clinician: understanding current methods.
AB  - The basics of molecular biology involve the replication of deoxyribonucleic acid
      and its transcription and translation into proteins. Biochemical assays such as
      the Southern blot analysis, polymerase chain reaction (PCR), Northern blot
      analysis, reverse-transcriptase PCR, microarray technology, Western blot
      analysis, immunohistochemistry, enzyme-linked immunosorbent assay, and flow
      cytometry utilize various aspects of molecular biology. To understand these
      assays requires some basic understanding of the principles of molecular biology.
      This paper provides basic information on the methodology and techniques used in
      these assays.

PMID- 16960036
TI  - The effects of clomipramine hydrochloride in cats with psychogenic alopecia: a
      prospective study.
AB  - A double-blind, placebo-controlled clinical trial was conducted to determine the
      efficacy of clomipramine hydrochloride in cats with psychogenic alopecia. Twenty
      five cats were randomly assigned to receive clomipramine hydrochloride (0.5 mg/kg
      orally q 24 hours) or placebo for 56 days. Eleven cats in each group completed
      the trial. The results of this study showed that clomipramine hydrochloride
      failed to demonstrate significant changes in the number of grooming bouts, hair
      regrowth, and the area of alopecia in cats with psychogenic alopecia when
      compared to a placebo. It was uncertain whether these results reflected a lack of
      drug efficacy, insufficient treatment duration, or an insufficient number of
      cases enrolled.

PMID- 16960037
TI  - Cardiovascular dysfunction in dogs associated with critical illnesses.
AB  - The records of 16 dogs with left ventricular dysfunction associated with severe
      systemic illness were reviewed. The most common diagnoses in affected dogs were
      sepsis and cancer. Despite left ventricular dysfunction, no dog presented with
      signs of congestive heart failure. Fifteen dogs were presented with generalized
      weakness as a part of their clinical complaint. Twelve (75%) of 16 dogs died or
      were euthanized within 15 days of admission to the hospital. The average time
      until death was 3.6 days.

PMID- 16960038
TI  - Outcomes of cats with oral tumors treated with mandibulectomy: 42 cases.
AB  - Medical records of 42 cats treated with mandibulectomy for oral neoplasia at
      eight institutions were reviewed to determine morbidity, progression-free
      interval, and survival time. Progression-free and survival rates at 1 and 2 years
      were 56% and 49%, and 60% and 57%, respectively. Cats with squamous cell
      carcinoma had significantly shorter survival than cats with fibrosarcoma or
      osteosarcoma. Seventy-two percent of cats were dysphagic or inappetent
      immediately postoperatively, and 12% never regained the ability to eat. Despite
      acute morbidity in 98% and long-term morbidity in 76% of cats, 83% of the 30
      owners providing information were satisfied with the outcome of mandibulectomy.

PMID- 16960039
TI  - The use of complementary and alternative therapies in dogs and cats with cancer.
AB  - The use of complementary and alternative medical therapies is becoming
      widespread. The objective of this study was to examine the use of complementary
      and alternative therapies in dogs and cats with cancer. The types of modalities
      used, the intended purpose for each modality, sources of information pet owners
      used, and the level of interest in these modalities were all evaluated.
      Information was obtained by written survey, and 254 owners agreed to participate.
      Complementary and alternative therapy use was commonplace, with 76% of surveyed
      owners reporting some use. When prayer for health reasons was excluded, the
      number of owners reporting use dropped to 65%. Nutritional supplements were the
      most commonly used therapy.

PMID- 16960040
TI  - A combination of oral cabergoline and double cloprostenol injections to produce
      third-quarter gestation termination in the bitch.
AB  - To assess the efficacy and safety of a combined cabergoline and cloprostenol
      protocol to terminate third-quarter pregnancy, 22 pregnant bitches that ranged
      from 35 to 45 days after mating were randomly assigned to a treatment group
      (n=13) or to an untreated control group (n=9). The animals were monitored for 12
      days, and pregnancy termination was confirmed by ultrasound examination. Twelve
      of the 13 treated bitches aborted within 9 days of the initiation of treatment
      (mean 4.6 days). Only mild side effects were observed. The control animals had
      normal gestational courses, as did the bitch that did not respond to the therapy.
      This combination of drugs appeared to be a practical, safe, and efficient
      abortifacient when used in third-quarter pregnancies.

PMID- 16960041
TI  - Subtotal ear canal ablation in 18 dogs and one cat with minimal distal ear canal
      pathology.
AB  - A modified technique for performing total ear canal ablations is described. This
      technique requires less dissection than the standard technique and maintains a
      portion of the distal vertical ear canal. Subtotal ear canal ablations were
      performed in 18 dogs and one cat for the treatment of otitis externa or masses of
      the horizontal ear canal. Animals with otitis externa had minimal involvement of
      the distal ear canal. Dermatological problems associated with the remaining ear
      canal and pinnae occurred in eight animals and resolved with medical management.
      Normal ear carriage was maintained in all animals with erect ears. Further
      investigation is required before the procedure can be recommended as a treatment
      for otitis externa not caused by masses or anatomical abnormalities of the
      horizontal ear canal in dogs with pendulous ears.

PMID- 16960042
TI  - Left lateral and left middle liver lobe torsion in a Saint Bernard puppy.
AB  - A 5-month-old, male Saint Bernard was presented for acute collapse and abdominal
      discomfort. Significant findings were a cranial abdominal mass, hemorrhagic
      abdominal effusion, anemia, and disseminated intravascular coagulation. An
      exploratory surgery revealed torsion of both the left lateral and middle liver
      lobes, a condition that has not been previously described in the veterinary
      literature. Torsion of one or more hepatic lobes is a rare condition but should
      be considered as a differential diagnosis for acute abdomen syndrome in both
      young and mature dogs. Early diagnosis and prompt surgical intervention may be
      curative.

PMID- 16960043
TI  - Combined use of surgery and radiation in the treatment of an intradural myxoid
      liposarcoma in a dog.
AB  - An intradural-extramedullary myxoid liposarcoma of the high cervical spine was
      diagnosed in a 9-year-old, spayed female Cavalier King Charles spaniel that was
      presented for a 2-month history of cervical pain and tetraparesis. Radiation
      therapy applied after surgery resulted in complete remission of the neurological
      deficits. The tumor recurred 18 months after surgical excision. A second surgery
      and another course of radiotherapy again resulted in complete remission of the
      clinical signs. The dog was euthanized 11 months after the second surgery because
      of tumor recurrence.

PMID- 16960044
TI  - Unilateral leiomyoma in the mesosalpinx of a dog.
AB  - Routine ultrasonographic evaluation of the genital organs of a 3-year-old terrier
      bitch revealed a mass at the level of the left ovary. The mass was located next
      to the caudal pole of the left kidney and ventrocaudal to the left ovary.
      Ultrasonographically, the uterus was not enlarged and had no luminal contents.
      Exploratory laparotomy revealed a mass attached to the left ovarian bursa with a
      small and thin pedicle. The mass had smooth margins, was whitish in color, and
      was lobulated on cut surface. The histopathological diagnosis of the mass was
      leiomyoma associated with the mesosalpinx.

PMID- 16960045
TI  - Ectopic ureterocele in a male dog: a case report and review of surgical
      management.
AB  - A 16-week-old, male border terrier was presented for urinary incontinence.
      Intravenous urography demonstrated a right-sided, extravesical ectopic
      ureterocele. Neoureterocystostomy and ureterocele omentalization were performed.
      Urinary incontinence persisted after surgery. Retrograde urethrography revealed
      communication between the ureterocele and urethra. Urinary incontinence resolved
      following partial ureterocelectomy and reconstruction of the proximal urethra.

PMID- 16960046
TI  - Care and use of feeding tubes in dogs and cats.
AB  - Feeding tubes are an accepted way of providing nutritional support for animals
      unable or unwilling to consume adequate calories on their own. This article
      provides information on the indications for the use of feeding tubes in small
      animals, the types of tubes available, and ways to initiate nutritional support
      once the tubes are in place. The pros and cons of the various tubes are
      discussed, as well as potential complications.

PMID- 16960047
TI  - Mexican chihuahua cheese: sensory profiles of young cheese.
AB  - Sensory profiles of fresh semihard Chihuahua cheese produced in the northern
      Mexican state of Chihuahua were developed to characterize the flavors and
      textures of this traditionally made Hispanic-style cheese. Multiple allotments of
      Chihuahua cheese, 9 brands made with raw milk (RM) and 5 brands made with
      pasteurized milk (PM), were obtained within 3 d of manufacture from 12 different
      cheese plants throughout Chihuahua, Mexico. Cheeses were shipped overnight to
      Wyndmoor, Pennsylvania, and flavor analyses were conducted within 14 to 18 d
      after manufacture. Four brands (2 RM and 2 PM cheeses) were then selected and
      multiple allotments were shipped at 3 distinct seasons over a 1-yr period for
      evaluation of flavor and texture. Microbial analysis was conducted prior to
      testing to ensure product safety. Descriptive analyses of cheese flavors and
      textures were conducted with panelists trained to use a universal or product
      specific Spectrum intensity scale, respectively. Sensory profiles of cheeses
      varied among the different manufacturers. The most prominent flavor attributes
      were salty, sour, diacetyl, cooked, whey, bitter, and milk-fat. The RM cheeses
      had more intense sour, bitter, and prickle scores than the PM cheeses. Many
      cheese texture attributes were similar, but RM cheeses were perceived as softer
      than PM cheeses. As the demand for Hispanic-style cheeses increases, defining and
      understanding the sensory attributes of traditionally made Mexican cheeses
      provides guidance to cheese manufacturers as new ways are explored to improve the
      production and shelf life of the cheeses.

PMID- 16960048
TI  - High-intensity pulsed electric field variables affecting Staphylococcus aureus
      inoculated in milk.
AB  - Staphylococcus aureus is an important milk-related pathogen that is inactivated
      by high-intensity pulsed electric fields (HIPEF). In this study, inactivation of
      Staph. aureus suspended in milk by HIPEF was studied using a response surface
      methodology, in which electric field intensity, pulse number, pulse width, pulse
      polarity, and the fat content of milk were the controlled variables. It was found
      that the fat content of milk did not significantly affect the microbial
      inactivation of Staph. aureus. A maximum value of 4.5 log reductions was obtained
      by applying 150 bipolar pulses of 8 mus each at 35 kV/cm. Bipolar pulses were
      more effective than those applied in the monopolar mode. An increase in electric
      field intensity, pulse number, or pulse width resulted in a drop in the survival
      fraction of Staph. aureus. Pulse widths close to 6.7 micros lead to greater
      microbial death with a minimum number of applied pulses. At a constant treatment
      time, a greater number of shorter pulses achieved better inactivation than those
      treatments performed at a lower number of longer pulses. The combined action of
      pulse number and electric field intensity followed a similar pattern, indicating
      that the same fraction of microbial death can be reached with different
      combinations of the variables. The behavior and relationship among the electrical
      variables suggest that the energy input of HIPEF processing might be optimized
      without decreasing the microbial death.

PMID- 16960049
TI  - Production of ingredient-type cheddar cheese with accelerated flavor development
      by addition of enzyme-modified cheese powder.
AB  - Fast-ripened Cheddar cheeses for ingredient purposes were produced by addition of
      a dried enzyme-modified cheese (EMC; 0.25 and 1 g/100 g of milled curd) at the
      salting stage during a standard Cheddar cheese-making procedure. Populations of
      starter and nonstarter lactic acid bacteria (NSLAB), levels of proteolysis and
      lipolysis, volatile analysis, and flavor development (by quantitative descriptive
      sensory analysis) were monitored over a 6-mo ripening period. Levels of free AA
      and free fatty acids were elevated in the experimental cheeses on d 1 because of
      inclusion of the EMC. Counts of NSLAB were also elevated in the experimental
      cheeses compared with the control cheese from the start of ripening. Levels of
      free AA were slightly elevated in the experimental cheeses at 1, 2, and 4 mo, but
      significantly greater accumulations were detected by 6 mo of ripening, with His,
      Leu, and glutamate reflecting the greatest increases. Levels of long-chain free
      fatty acids increased up to 2 mo, indicating an initial stimulation of lipolysis,
      but had decreased by 6 mo, indicating greater catabolism, probably caused by
      NSLAB and increased starter lysis. Principal component analysis of the volatile
      compounds showed few differences in the aroma profiles among the cheeses up to 4
      mo of ripening, but a large separation of the cheeses supplemented with EMC
      relative to the control was observed by 6 mo. Sensory analysis of the cheeses
      with added EMC showed an acceleration of 2 mo in flavor development compared with
      the control cheese with the addition of 1 g/100 g of EMC developing a flavor
      profile at 4 mo similar to the control cheese at 6 mo of ripening. However,
      atypical Cheddar flavors developed on prolonged storage. This study shows the
      potential of adding EMC during Cheddar production to produce a fast-ripened
      ingredient-type Cheddar cheese.

PMID- 16960050
TI  - Real-time polymerase chain reaction for quantitative detection of histamine
      producing bacteria: use in cheese production.
AB  - Biogenic amines are toxic substances that appear in foods and beverages as a
      result of AA decarboxylation. The enzyme histidine decarboxylase catalyzes the
      decarboxylation of histidine to histamine, the biogenic amine most frequently
      involved in food poisoning. The aim of the present work was to develop a real
      time quantitative PCR assay for the direct detection and quantification of
      histamine-producing strains in milk and cheese. A set of primers was designed,
      based on the histidine decarboxylase gene sequence of different gram-positive
      bacteria. The results show the proposed procedure to be a rapid (total processing
      time < 2 h), specific and highly sensitive technique for detecting potential
      histamine-producing strains. Chromatographic methods (HPLC) verified the capacity
      of real-time quantitative PCR to correctly quantify histamine accumulation.

PMID- 16960051
TI  - Fluorescein thiocarbamoyl-kappa-casein assay for the specific testing of milk
      clotting proteases.
AB  - Milk-clotting proteases, which are widely used in the cheese-making industry, are
      enzymes that use soluble caseins as their preferential substrates. Here, we
      propose a modification to a method previously described for the specific
      determination of milk-clotting proteases by using kappa-casein labeled with
      fluorescein isothiocyanate as substrate. Validation of the modified method was
      confirmed using natural bacterial, fungal, plant, and animal milk-clotting
      proteases, as well as a milk-clotting enzyme of recombinant origin. The new
      modified method described here allowed specific quantification of the activity of
      milk-clotting proteases in a very sensitive way and permitted determination of
      the appropriate kinetic parameters of all the enzymes tested, consistent with
      their origin and degree of purity.

PMID- 16960052
TI  - Microfiltration of raw whole milk to select fractions with different fat globule
      size distributions: process optimization and analysis.
AB  - We present an extensive description and analysis of a microfiltration process
      patented in our laboratory to separate different fractions of the initial milk
      fat globule population according to the size of the native milk fat globules
      (MFG). We used nominal membrane pore sizes of 2 to 12 microm and a specially
      designed pilot rig. Using this process with whole milk [whose MFG have a volume
      mean diameter (d43) = 4.2 +/- 0.2 microm] and appropriate membrane pore size and
      hydrodynamic conditions, we collected 2 extremes of the initial milk fat globule
      distribution consisting of 1) a retentate containing large MFG of d43 = 5 to 7.5
      microm (with up to 250 g/kg of fat, up to 35% of initial milk fat, and up to 10%
      of initial milk volume), and 2) a permeate containing small MFG of d43 = 0.9 to
      3.3 microm (with up to 16 g/kg of fat, up to 30% of initial milk fat, and up to
      83% of initial milk volume and devoid of somatic cells). We checked that the
      process did not mechanically damage the MFG by measuring their zeta-potential.
      This new microfiltration process, avoiding milk aging, appears to be more
      efficient than gravity separation in selecting native MFG of different sizes. As
      we summarize from previous and new results showing that the physico-chemical and
      technological properties of native milk fat globules vary according to their
      size, the use of different fat globule fractions appears to be advantageous
      regarding the quality of cheeses and can lead to new dairy products with adapted
      properties (sensory, functional, and perhaps nutritional).

PMID- 16960053
TI  - Diversity of Streptococcus thermophilus phages in a large-production cheese
      factory in Argentina.
AB  - Phage infections still represent a serious risk to the dairy industry, in which
      Streptococcus thermophilus is used in starter cultures for the manufacture of
      yogurt and cheese. The goal of the present study was to analyze the biodiversity
      of the virulent S. thermophilus phage population in one Argentinean cheese plant.
      Ten distinct S. thermophilus phages were isolated from cheese whey samples
      collected in a 2-mo survey. They were then characterized by their morphology,
      host range, and restriction patterns. These phages were also classified within
      the 2 main groups of S. thermophilus phages (cos- and pac-type) using a newly
      adapted multiplex PCR method. Six phages were classified as cos-type phages,
      whereas the 4 others belonged to the pac-type group. This study illustrates the
      phage diversity that can be found in one factory that rotates several cultures of
      S. thermophilus. Limiting the number of starter cultures is likely to reduce
      phage biodiversity within a fermentation facility.

PMID- 16960054
TI  - Extraction and partial characterization of proteolytic activities from the cell
      surface of Lactobacillus helveticus Zuc2.
AB  - Proteolytic activities were extracted from a dairy Lactobacillus helveticus
      strain and partially characterized. A first cell envelope proteinase (CEP) was
      extracted using a high ionic strength buffer, both in the presence and in the
      absence of Ca2+. Moreover, cell treatment by 5 M LiCl allowed for the selective
      removal of the S-layer protein and CEP, suggesting an enzyme ionic linkage to the
      cell envelope similar to that observed for the Slayer structure. The enzyme
      specificity against alpha(s1)-CN (f1-23) showed unusual activity on the Lys3-His4
      bond compared with other proteinases of the same species. A second proteinase
      appeared to be linked to the cell membrane because it was extractable only after
      membrane disgregation by detergents. Its specificity against CN fractions and
      alpha(s1)-CN (f1-23) was different from that of the first CEP; moreover, the
      measured activity was lower than that of CEP.

PMID- 16960055
TI  - Presynchronization with gonadotropin-releasing hormone does not improve fertility
      in Holstein heifers.
AB  - Holstein dairy heifers were randomly assigned to 1 of 2 treatments to determine
      whether a presynchronization strategy using GnRH would improve reproductive
      performance after synchronization of ovulation and timed artificial insemination
      (TAI). Heifers (n = 82) in the first treatment (GPG) received a hormonal protocol
      for synchronization of ovulation and TAI (100 microg of GnRH, d 0; 25 mg of
      PGF2alpha, d 6; 100 microg of GnRH + TAI, d 8); whereas heifers (n = 84) in the
      second treatment (GGPG) received GPG, but with the addition of a GnRH injection
      (100 microg) 7 d before initiation of the GPG protocol. The proportion of heifers
      receiving AI before d 8 was similar for GPG (4.9%) and GGPG (9.5%), and the
      proportion of heifers diagnosed pregnant 30 d after AI did not differ between
      treatments (45 vs. 51%, respectively). Treatment did not affect the proportion of
      heifers ovulating after the second GnRH injection or the proportion in which a
      corpus luteum regressed after treatment with PGF2alpha. In conclusion,
      presynchronization with GnRH 7 d before initiation of synchronization of
      ovulation using GnRH and PGF2alpha did not affect the proportion of heifers
      expressing estrus before TAI or improve synchronization response or fertility to
      the synchronization protocol.

PMID- 16960056
TI  - Extending the potential of evaporative cooling for heat-stress relief.
AB  - Factors were analyzed that limit the range of environmental conditions in which
      stress from heat may be relieved by evaporative cooling in shaded animals.
      Evaporative cooling reduces air temperature (Ta), but increases humidity.
      Equations were developed to predict Ta reduction as a function of ambient
      temperature and humidity and of humidity in cooled air. Predictions indicated
      that a reduction of Ta becomes marginal at humidities beyond 45%. A reduction of
      Ta lessens with rising ambient Ta. The impact of increasing humidity on
      respiratory heat loss (Hre) was estimated from existing data published on
      Holstein cattle. Respiratory heat loss is reduced by increased humidity up to
      45%, but is not affected by higher humidity. Skin evaporative and sensible heat
      losses are determined not only by the humidity and temperature gradient, but also
      by air velocity close to the body surface. At higher Ta, the reduction in
      sensible heat loss is compensated for by an increased demand for Hre. High Hre
      may become a stressor when panting interferes with resting and rumination.
      Effects of temperature, humidity, air velocity, and body surface exposure to free
      air on Hre were estimated by a thermal balance model for lactating Holstein cows
      yielding 35 kg/d. The predictions of the simulations were supported by
      respiratory rate observations. The Hre was assumed to act as a stressor when
      exceeding 50% of the maximal capacity. When the full body surface was exposed to
      a 1.5 m/s air velocity, humidity (15 to 75%) had no significant predicted effect
      on Hre. For an air velocity of 0.3 m/s, Hre at 50% of the maximum rate was
      predicted at 34, 32.5, and 31.5 degrees C for relative humidities of 55, 65, and
      75%, respectively. Similar results were predicted for an animal with two-thirds
      of its body surface exposed to 1.5 m/s air velocity. If air velocity was reduced
      for such animals to 0.3 m/s, the rise in Hre was expected to occur at
      approximately 25 degrees C and 50% relative humidity. Maximal rates of Hre were
      estimated at 27 to 30 degrees C when ambient humidity was 55% relative humidity
      and higher. High humidity may stress animals in evaporative cooling systems.
      Humidity stress may be prevented by a higher air velocity on the body surface of
      the animal, particularly in sheltered areas in which the exposed body surface is
      reduced, such as mangers and stalls. This may extend the use of evaporative
      cooling to less dry environments.

PMID- 16960057
TI  - Conjugated linoleic acid reduces phorbol ester-induced prostaglandin F2alpha
      production by bovine endometrial cells.
AB  - Recent interest in conjugated linoleic acid (CLA) research stems from the well
      documented anticarcinogenic, antiatherogenic, antidiabetic, and antiobesity
      properties of CLA in animal models. The objective of this study was to examine
      the effects of 2 CLA isomers (cis-9,trans-11 and trans-10,cis-12) on phorbol
      12,13-dibutyrate (PDBu)-induced PGF2alpha production in cultured bovine
      endometrial (BEND) cells. Confluent BEND cells were incubated in the absence
      (control) or presence of 100 microM each of linoleic acid, cis-9,trans-11 CLA, or
      trans-10,cis-12 CLA for 24 h. After incubation, cells were rinsed and then
      stimulated with PDBu (100 ng/mL) for 6 h. Compared with untreated cells, PDBu
      stimulated PGF2alpha secretion (+25-fold) within 6 h. The increases in
      PGF(2alpha) secretion were paralleled by signifi-cant induction of prostaglandin
      endoperoxide synthase-2 (PGHS-2) mRNA (+63-fold) and protein (+1.6-fold)
      expression. In spite of stimulatory effects on PGHS-2 and peroxisome proliferator
      activated receptor delta (PPARdelta) mRNA responses, CLA greatly decreased
      PGF2alpha production by PDBu-stimulated BEND cells. There was no evidence for
      PDBu or CLA modulation of PPARdelta protein synthesis in cultured BEND cells.
      Results indicated that CLA modulation of PGF2alpha production by BEND cells was
      not mediated through PGHS-2 or PPARdelta gene repression.

PMID- 16960058
TI  - Body condition assessment using digital images.
AB  - This project assessed the ability to assign a body condition score (BCS) to a
      dairy cow from digital photographs or videos. Images were taken from the rear of
      the cow at a 0 to 20 degrees angle relative to the tail head. Four observers
      assigned a BCS to each of 57 cows at a farm visit (live, farm 1) and later from a
      photograph (photo). Means +/- standard deviations of BCS by method and observer
      were as follows: live = 3.25 +/- 0.51, 3.42 +/- 0.49, 3.32 +/- 0.58, 3.13 +/-
      0.62; photo = 3.36 +/- 0.52, 3.32 +/- 0.43, 3.44 +/- 0.62, 3.14 +/- 0.6 for
      observers 1 to 4, respectively. Body condition score means differed across
      observers for live (observer 2 higher and observer 4 lower, compared with
      observers 1 and 3) and photo methods (observer 3 lower, compared with observers
      1, 2, and 3); however, within observer, the mean live BCS did not differ from the
      mean photo BCS. Correlation coefficients between BCS assigned live and from
      photos were 0.84, 0.82, 0.82, and 0.90 for observers 1 to 4, respectively.
      Subsequently, observer 1 visited 2 farms, assigned a live BCS, and digitally
      photographed 187 cows (56 and 131 cows from farms 2 and 3, respectively).
      Observers 2, 3, and 4 assigned a BCS from the photographs. Means +/- standard
      deviations of BCS by observer (method) were 1 (live) 3.35 +/- 0.55; 2 (photo)
      3.33 +/- 0.49; 3 (photo) 3.60 +/- 0.54; and 4 (photo) 3.26 +/- 0.62. The mean BCS
      for observer 3 was higher and that for observer 4 was lower than for observers 1
      and 2. Correlation coefficients between observer 1 and observers 2 through 4 were
      0.78, 0.76, and 0.79, respectively. Observer 1 assigned a BCS to 41 cows at a
      farm visit and 3 wk later assessed the BCS of cows from a video taken at a farm
      visit by a different individual. Cows were restrained in headlocks at a feed bunk
      when assessing BCS and for video production. No difference was detected for the
      mean BCS, for the standard deviation of the mean BCS, or in the distribution of
      BCS between the live and video assessments. Mean and SD for 17 groups of Holstein
      cows from 20 farms were used to generate 10,000 random samples of BCS. Groups of
      25, 50, 100, and 150 cows were created from the random samples, and estimates of
      mean BCS were determined by sampling 3 to 80% of the group. Estimates of mean BCS
      with a sample size of 30% or more from a group of cows fell within the 95%
      confidence limit of the true mean more than 98% of the time. Digital photographs
      provide adequate imaging for assessment of BCS. Sampling 30% of a group should be
      adequate to assess the mean BCS. Video imaging allowed a rapid assessment of BCS
      but did not permit identification of individual cows.

PMID- 16960059
TI  - Technical note: measurement of ferritin in bovine milk and its clinical
      significance.
AB  - A quantitative ELISA was developed for bovine milk ferritin with an assay limit
      of 0.16 ng/mL of bovine spleen ferritin. Ferritin-binding activity was detected
      in bovine milk samples, and this binding activity was inhibited by increasing
      ionic strength with the addition of 0.5 M (NH4)2SO4. Heat treatment (60 degrees
      C, 20 min) of bovine milk in the presence of 0.5 M (NH4)2SO4 resulted in a 15 to
      58% increase in ferritin concentrations compared with untreated samples. Although
      the recovery of bovine spleen ferritin added to milk was still low (55 to 90%),
      even in the presence of increased ionic strength with 0.5 M (NH4)2SO4, recovery
      was improved by heat treatment at 60 degrees C for 20 min (92 to 95%). Milk
      ferritin concentrations in 30 milk samples from quarters of 25 cows with mastitis
      (mean +/- SE: 134.2 +/- 28.7 ng/mL) were significantly higher than those in 17
      quarter milk samples from 17 noninfected lactating cows (7.2 +/- 1.2 ng/mL),
      suggesting that bovine milk contains putative ferritin-binding proteins that
      inhibit immunoassay for milk ferritin and that bovine milk ferritin is an
      indicator of IMI.

PMID- 16960060
TI  - Deferoxamine reduces tissue damage during endotoxin-induced mastitis in dairy
      cows.
AB  - The protective effects of 3 antioxidants on polymorphonuclear neutrophil-induced
      damage to mammary cells were evaluated in vivo using an endotoxin-induced
      mastitis model. Fifteen healthy, midlactation cows with no history of clinical
      Escherichia coli mastitis were randomly assigned to 1 of the 3 treatment groups
      corresponding to each modulator to be evaluated, that is, deferoxamine, catechin,
      and glutathione ethyl ester. Each cow had 1 quarter infused with saline and 1
      quarter infused with the selected modulator; a third quarter was infused with
      lipopolysaccharides (LPS), whereas the fourth quarter received a combination of
      LPS and the modulator. Infusion of LPS caused acute mastitis as determined by
      visual observations and by large increases in milk somatic cell count, BSA, and
      proteolytic activity. These parameters were not affected by antioxidant
      administration. The extent of cell damage was evaluated by measuring milk levels
      of lactate dehydrogenase and N-acetyl-beta-D-glucosaminidase activity. Levels of
      these parameters were several times higher after LPS administration. Intramammary
      infusions of catechin or glutathione ethyl ester did not exert any protective
      effect, whereas infusion of deferoxamine, a chelator of iron, decreased milk
      lactate dehydrogenase and NA-Gase activity, suggesting a protective effect
      against neutrophil-induced damage. The protective effect of deferoxamine was also
      evidenced by a lower milk level of haptoglobin. The proteolytic activity of
      mastitic milk was not influenced by the presence of deferoxamine. Overall, our
      results suggest that local infusion of deferoxamine may be an effective tool to
      protect mammary tissue against neutrophil-induced oxidative stress during bovine
      mastitis.

PMID- 16960061
TI  - An evaluation of the seasonality of veterinary treatments for lameness in UK
      dairy cattle.
AB  - Of the 4 main diseases causing lameness in UK dairy cattle, 2 (digital dermatitis
      and foul-in-the-foot, or interdigital necrobacillosis) are infectious diseases
      that are commonly associated with similar underfoot conditions, and 2 (sole ulcer
      and white-line disease) result from subclinical laminitis. Comparison of the
      seasonality of these 2 diseases can identify whether their own unique risk
      factors are more important than the risk factors they share. Using a database
      from 46 veterinarians distributed across the United Kingdom, the seasonality of
      treatments for these 4 diseases was evaluated. This analysis showed that the
      seasonality of lameness in UK dairy cattle was significantly reduced in
      comparison with previous reports from the 1980s. This was primarily due to 1) a
      reduction in the seasonality of digital dermatitis (outbreaks of which accounted
      for 6.7% of veterinary reports), with only 60% of reports during the winter as
      opposed to 72% in earlier studies, and 2) a change in the seasonality of white
      line disease from a disease that was most commonly seen in the winter (55% of
      reports) to a disease that was most commonly reported in the late summer or early
      autumn, with significantly more reports in August and October than in February.
      Comparison of the seasonality of digital dermatitis and foul-in-the-foot showed a
      significant difference in the seasonality of the 2 diseases, with foul-in-the
      foot being significantly more common compared with digital dermatitis in June and
      August. This implies that significant risk factors exist for digital dermatitis
      that are not as important for foul-in-the-foot. The difference in the seasonality
      of sole ulcer and white-line disease was even more marked, with white-line
      disease being significantly more common than sole ulcer from August to October,
      despite these diseases being more closely linked in the literature than digital
      dermatitis and foul-in-the-foot. This comparison shows that the seasonality of
      lameness has changed in the United Kingdom and that white-line disease has
      significantly different risk factors than sole ulcer.

PMID- 16960062
TI  - Effect of different premilking manual teat-cleaning methods on bacterial spores
      in milk.
AB  - Different teat-cleaning methods were evaluated to determine their effect on the
      presence of spores from anaerobic bacterial spore-formers in the milk. Artificial
      contamination was used to achieve uniform contamination of teats to reduce the
      number of cows and samples needed in the experiments and still obtain adequate
      power to detect differences among tested methods. Teats were contaminated
      experimentally with a large amount of Clostridium tyrobutyricum spores in a
      manure-water slurry. Various types of dry and moistened towels and different
      combinations of methods using soap or 2 types of towels, together with cleaning
      times of 10 or 20 s, were compared in 2 Latin square-designed experiments with 7
      cows, 7 treatments, and 4 replications in each experiment. In comparison with
      control (no cleaning and no forestripping), cleaning teats with dry paper towels
      for 10 s reduced concentration of spores in milk by 45 to 50%. A 50 to 74%
      reduction was achieved using different types of moist towels for 10 s. Methods
      using 2 towels, soap, or a longer cleaning time reduced bacterial contamination
      by 85 to 91%. The most effective methods in reducing milk spore content (96%
      reduction) were use of a moist washable towel with or without soap followed by
      drying with a dry paper towel, for a total time of 20 s per cow. One of the best
      cleaning methods was studied in an additional experiment to determine the effect
      of different teat contamination mixtures. The Latin square-designed experiment
      with 8 cows, 8 treatments, and 2 replications showed that cleaning was
      independent of the tested contamination matrix (manure, soil, or sawdust), type
      of spores (Cl. tyrobutyricum and Bacillus cereus), or degree of contamination
      (manure or extra manure).

PMID- 16960063
TI  - Economic value of pregnancy in dairy cattle.
AB  - The objective of this study was to estimate the value of pregnancy for dairy
      cows. Effects of the stage of gestation, stage of lactation, lactation number,
      milk yield, milk price, replacement heifer cost, probability of pregnancy,
      probability of involuntary culling, and breeding decisions were studied. A
      bioeconomic model was used, and breeding and replacement decisions were
      optimized. A general Holstein herd in the United States was modeled. The average
      value of a new pregnancy was $278. The value of a new pregnancy increased with
      days in milk early in lactation but typically decreased later in lactation.
      Relatively high-producing cows and first-lactation cows reached greater values,
      and their values peaked later in lactation. The average cost of a pregnancy loss
      (abortion) was $555. The cost of a pregnancy loss typically increased with
      gestation length. Sensitivity analyses showed that an increased probability of
      pregnancy, an increased persistency of milk yield, and a smaller replacement
      heifer cost greatly reduced the average value of a pregnancy. The value of a new
      pregnancy was negative for relatively high-producing first-lactation cows when
      persistency of lactation and the probability of pregnancy were increased.
      Breeding was delayed when the value of pregnancy was negative. Changes in milk
      price, absolute milk yield, and probability of involuntary culling had less
      effect on the value of pregnancy. The value of pregnancy and optimal breeding
      decisions for individual cows were greatly dependent on the predicted daily milk
      yield for the remaining period of lactation. An improved understanding of the
      value of pregnancy may support decision making in reproductive management when
      resources are limited.

PMID- 16960064
TI  - Conventional identification of Streptococcus uberis isolated from bovine mastitis
      in Argentinean dairy herds.
AB  - The objective of this study was to evaluate a conventional scheme for identifying
      Streptococcus uberis strains isolated from bovine mastitis. Seventy-five gram
      positive, catalase-negative cocci were collected from cows with mastitis from 19
      dairy herds located in the east-central region of Argentina. Five American Type
      Culture Collection strains and bovine isolates were identified by the API 20
      Strep system and by restriction fragment length polymorphism analysis of 16S
      rDNA. A conventional scheme based on 11 biochemical tests was selected for
      identification of Strep. uberis strains: the Christie-Atkins-Munch-Petersen
      reaction; hydrolysis of Arg, esculin, and sodium hippurate; growth in inulin,
      mannitol, raffinose, salicin, and sorbitol; and growth at 45 degrees C and in
      6.5% NaCl. Reference strains and 25 bovine isolates were classified accurately to
      the species level by the conventional scheme in a blind assay. Each reference
      strain and each bovine isolate were identified as belonging to the same species
      following these 3 methods. The remaining 50 isolates identified as Strep. uberis
      by the API 20 Strep system and 16S rDNA RFLP were assayed by the conventional
      scheme. This scheme correctly identified 47 (94%) of 50 isolates as Strep. uberis
      by comparing their biochemical profile with that of the reference strain. Three
      (6%) of the 50 isolates were classified as Strep. uberis by the API 20 Strep
      system and by 16S rDNA RFLP and were identified as Enterococcus faecalis by the
      conventional scheme. Thirty percent of the Strep. uberis strains showed
      biochemical profiles identical to the Strep. uberis American Type Culture
      Collection 27958 strain. Seventy percent of the Strep. uberis strains
      demonstrated variability compared with the reference strain, resulting in 19
      different biochemical profiles. The conventional scheme proposed in this study
      resulted in a relatively low number of misidentifications and could biochemically
      identify not only typical, but also atypical Strep. uberis strains. This
      conventional scheme can be considered an adequate method for identifying Strep.
      uberis strains isolated from bovine mastitis because of its affordable cost in
      developing countries, and it may contribute to determining the frequency of
      isolation of Strep. uberis strains in Argentinean dairy herds.

PMID- 16960065
TI  - Effects of dietary unsaturated fatty acids on oocyte quality and follicular
      development in lactating dairy cows in summer.
AB  - Dietary sources of fatty acids were evaluated for their influence on oocyte
      quality and follicular development using 54 lactating cows in summer. Fat
      supplements were 1) sunflower oil (80% cis 18:1), 2) Ca salt of transoctadecenoic
      acids (57% trans 18:1), 3) Ca salt of vegetable oils (30% 18:2), and 4) linseed
      oil (56% 18:3 and 16% 18:2). Fats were fed at 1.35% of dietary dry matter
      beginning at 5 wk prior to expected calving date and at 1.5% (oils) and 1.75% (Ca
      salts) of dietary dry matter for 15 wk after parturition. Four days following a
      programmed induced ovulation, 5 transvaginal oocyte aspirations were performed 3
      or 4 d apart. Three days after the last aspiration, PGF2alpha was injected,
      followed 3 d later by a GnRH injection and a timed artificial insemination (d 0)
      16 to 20 h later. For the first 4 aspirations, oocytes grading 1 or 2 were used
      for in vitro embryo production. Total cell number and the proportion of terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive
      blastomeres were analyzed at d 8. At the fifth aspiration, the occurrence of
      metaphase II, group II caspase activity, and TUNEL labeling were determined after
      oocyte maturation. A total of 1,011 oocytes were collected. The proportion of
      oocytes with high caspase activity was greater for grade 3 compared with grades 1
      and 2 (37.5 vs. 1.54 and 1.61%). Feeding polyunsaturated fatty acids, as compared
      with monosaturated fatty acids, failed to affect oocyte quality, as demonstrated
      by subsequent embryo development. Cows fed 18:2- or 18:3-enriched diets had a
      larger preovulatory follicle at insemination and subsequent volume of the corpus
      luteum compared with those fed cis 18:1 or trans 18:1 diets (16.8, 16.2 vs. 15.0,
      14.9 +/- 0.7 mm; 7,323, 8,208 vs. 6,033, 5,495 +/- 644 mm3, respectively). The
      previously documented benefits of polyunsaturated fatty acids on reproductive
      performance appear to reflect actions at alternative biological windows in
      lactating dairy cows.

PMID- 16960066
TI  - Evaporative tunnel cooling of dairy cows in the southeast. I: effect on body
      temperature and respiration rate.
AB  - The techniques used to mitigate the effects of heat stress on lactating dairy
      cows are often overwhelmed in the southeastern United States, where elevated heat
      and humidity often persist for extended periods. A model free-stall barn located
      at the North Mississippi Branch Experiment Station in Holly Springs was used to
      evaluate the potential of tunnel ventilation with evaporative cooling to
      alleviate heat stress in lactating dairy cows. Two studies were conducted using 2
      groups of 10 lactating Holsteins housed in the tunnel barn (inside) and 2 groups
      of matched herdmates housed in an adjacent covered free-stall barn (outside),
      which was cooled by fans and sprinklers during 2001 or by shade and fans alone in
      2003. Peak daytime temperatures inside were 5.2 +/- 0.18 degrees C below that
      outside in 2001 and 3.1 +/- 0.20 degrees C lower in 2003. Although evaporative
      cooling increased humidity by 22%, cows housed in the tunnel barn received 84%
      less exposure to moderate heat stress (temperature-humidity index > 80) in both
      years. Cooling cows with evaporative tunnel ventilation reduced respiration rates
      by 15.5 +/- 0.56 breaths/min and rectal temperatures by 0.6 +/- 0.02 degrees C
      compared with shade and fans alone in 2003. Cooling cows with evaporative tunnel
      ventilation reduced respiration rates by 13.1 +/- 0.78 breaths/min and rectal
      temperatures by 0.4 +/- 0.03 degrees C compared with fans and sprinklers in 2001.
      Thus, tunnel ventilation cooling dramatically reduced the exposure to heat stress
      and improved the comfort of lactating dairy cows when compared with traditional
      cooling technologies under the conditions present in the southeastern United
      States.

PMID- 16960067
TI  - Evaporative tunnel cooling of dairy cows in the southeast. II: impact on
      lactation performance.
AB  - Heat stress has a dramatic impact on the dairy industry, reducing production and
      profitability throughout the southeastern United States. In many regions,
      management techniques can be used to mitigate the effects of heat stress, but
      available cooling technologies are often overwhelmed by the conditions of chronic
      heat stress present in southeastern United States. Although combining tunnel
      ventilation and evaporative cooling (evaporative tunnel cooling) seems to provide
      superior cooling for dairy cows, there is a dearth of reports on the impact of
      this technology on milk production. A model evaporative tunnel cooling facility
      in northern Mississippi was studied using 2 groups of 10 lactating Holstein cows
      housed in the tunnel barn and 2 groups of 10 matched herdmates housed in an
      adjacent naturally ventilated free-stall barn. Two 10-wk trials were performed in
      2 yr beginning June 25, 2001, and May 26, 2003, in which cows housed outside were
      cooled by traditional fans and shade alone (2003) or with sprinklers (2001). In
      both years, the use of evaporative tunnel cooling decreased exposure to
      conditions of moderate heat stress by 84%. Cows cooled by evaporative tunnel
      ventilation increased feed intake by 12 and 11% over cows housed outside in 2001
      and 2003, respectively. Evaporative tunnel cooling had no effect on milk
      composition, but increased milk yield over the 10-wk trial by 2.6 +/- 0.27 and
      2.8 +/- 0.19 kg/cow per day in 2001 and 2003, respectively. In addition, somatic
      cell count was decreased 27 to 49% by evaporative tunnel cooling. Thus, under the
      range of environmental conditions present, evaporative tunnel cooling reliably
      reduced exposure to conditions of heat stress and improved milk production of
      lactating dairy cows during the summer season.

PMID- 16960068
TI  - Effect of varying dietary ratios of alfalfa silage to corn silage on production
      and nitrogen utilization in lactating dairy cows.
AB  - Twenty-eight (8 ruminally cannulated) lactating, multiparous Holstein cows were
      blocked by DIM and randomly assigned to 7 replicated 4 x 4 Latin squares (28-d
      periods) to investigate the effects of different dietary ratios of alfalfa silage
      (AS) to corn silage (CS) on production, N utilization, apparent digestibility,
      and ruminal metabolism. The 4 diets contained (dry matter basis): A) 51% AS, 43%
      rolled high-moisture shelled corn (HMSC), and 3% solvent soybean meal (SSBM); B)
      37% AS, 13% CS, 39% HMSC, and 7% SSBM; C) 24% AS, 27% CS, 35% HMSC, and 12% SSBM;
      and D) 10% AS, 40% CS, 31% HMSC, and 16% SSBM. Dietary crude protein contents
      were 17.2, 16.9, 16.6, and 16.2% for diets A, B, C, and D. All 4 diets were high
      in energy, averaging 49% nonfiber carbohydrates and 24% neutral detergent fiber.
      Intake of dry matter, yield of milk, 3.5% fat-corrected milk and fat, milk fat
      content, and apparent digestibility of neutral detergent fiber and acid detergent
      fiber all decreased linearly when CS replaced AS. Effects on fiber digestion and
      milk fat may have been due to increasing fluctuation in ruminal pH and time the
      pH remained < 6.0 when CS replaced AS. Milk protein content increased linearly
      with increasing CS, but there were no differences in protein yield. There were
      linear increases in apparent N efficiency and decreases in N excreted in urine
      and feces when CS replaced AS. Production was depressed on the diet highest in
      CS. Quadratic analysis indicated that milk and protein yields were maximal at
      dietary AS:CS ratios of, respectively, 37:13 and 31:19. No diet minimized N
      excretion without negatively affecting production. Diet C, with an AS:CS ratio of
      24:27, was the best compromise between improved N efficiency and sustained
      production. Because CS is complementary with AS, it is recommended that CS be fed
      in AS-based diets to maintain milk yield while improving N utilization.

PMID- 16960069
TI  - Effect of varying dietary ratios of alfalfa silage to corn silage on omasal flow
      and microbial protein synthesis in dairy cows.
AB  - Eight ruminally cannulated multiparous Holstein cows that were part of a larger
      production trial were used to study the effects of varying dietary ratios of
      alfalfa silage (AS) to corn silage (CS) on omasal flow of nutrients and microbial
      protein. Cows were blocked by DIM and randomly assigned to 2 replicated 4 x 4
      Latin squares (28-d periods). Diets fed contained (dry matter basis): A) 51% AS,
      43% rolled high-moisture shelled corn (HMSC), and 3% solvent soybean meal (SSBM);
      B) 37% AS, 13% CS, 39% HMSC, and 7% SSBM; C) 24% AS, 27% CS, 35% HMSC, and 12%
      SSBM; or D) 10% AS, 40% CS, 31% HMSC, and 16% SSBM. Crude protein (CP) contents
      were 17.2, 16.9, 16.6, and 16.2% for diets A, B, C, and D. All 4 diets were high
      in energy, averaging 49% nonfiber carbohydrates and 24% neutral detergent fiber.
      Total microbial nonammonia nitrogen flow was lower on diet D (423 g/d) compared
      with diets A (465 g/d), B (479 g/d), and C (460 g/d). A significant quadratic
      effect indicated that microbial protein synthesis was maximal at 38% AS. Supply
      of rumen-degraded protein decreased linearly from 3,068 g/d (diet A) to 2,469 g/d
      (diet D). Omasal flow of rumen-undegraded protein did not differ among diets and
      averaged 1,528 g/d. However, when expressed as a percentage of dry matter intake,
      rumen-undegraded protein increased linearly from 5.59% (diet A) to 6.13% (diet
      D), probably because CP from SSBM was more resistant to degradation than CP from
      AS. Essential AA flow was lowest on diet D, and Lys flow tended to be lower on
      diet D, which may explain the lower milk and protein yields observed on that
      diet.

PMID- 16960070
TI  - Milk odd- and branched-chain fatty acids in relation to the rumen fermentation
      pattern.
AB  - The objectives of this study were 1) to determine whether a relationship exists
      between molar proportions of volatile fatty acids in the rumen and milk odd-and
      branched-chain fatty acid concentrations (i.e., iso C13:0, anteiso C13:0, iso
      C14:0, C15:0, iso C15:0, anteiso C15:0, iso C16:0, C17:0, iso C17:0, anteiso
      C17:0, and cis-9 C17:1); and 2) to evaluate the accuracy of prediction of the
      latter equations using an independent data set. For development of the regression
      equations, individual cow data from 10 feeding experiments with rumen-fistulated
      dairy cows were used, resulting in a data set of 148 observations. Milk odd- and
      branched-chain fatty acids were closely related to the molar proportions of
      acetate (SE = 15.3 mmol/mol), propionate (SE = 14.7 mmol/mol), and butyrate (SE =
      9.2 mmol/mol). These regression equations were further validated using data from
      the literature (n = 14). Evaluation of these prediction equations using the
      independent data set resulted in a root mean square prediction error of 3.0, 9.0,
      and 8.9% of the observed mean for acetate, propionate, and butyrate,
      respectively. In addition, less then 5% of the mean square prediction error was
      due to line bias. This suggests that the currently developed prediction equations
      based on milk odd- and branched-chain fatty acids show potential to predict molar
      proportions of individual volatile fatty acids in the rumen.

PMID- 16960071
TI  - Technical note: development of a tool to insert abomasal infusion lines into
      dairy cows.
AB  - A tool was developed to aid in ruminal insertion of abomasal infusion lines into
      dairy cows. The tool consisted of 2 pieces cut from polyvinyl chloride pipe. The
      first piece of pipe, the insertion tool, contained a groove that held the
      flexible plastic flange that is on the end of the infusion line. The insertion
      tool containing the flange was inserted into the ruminal cannula, through the
      sulcus omasi, and into the abomasum. The second piece of pipe, the delivery tool,
      was threaded through the insertion tool, and it was used to dislodge the flange
      from the insertion tool and into the abomasum.

PMID- 16960072
TI  - Technical note: estimating statistical power of mixed models used in dairy
      nutrition experiments.
AB  - Statistical power is defined as the probability of correctly rejecting the null
      hypothesis. Power calculations may be useful in planning experiments. The
      objective of this technical note is to outline an applied method that estimates
      statistical power of a dairy nutrition experiment that employs a Latin square as
      the experimental design. Because the SAS MIXED procedure (PROC MIXED) is commonly
      used to analyze data sets, this note outlines basic programming procedures that
      may be used to estimate statistical power of a mixed model using this procedure.

PMID- 16960073
TI  - Milk production and composition from cows fed small amounts of fish oil with
      extruded soybeans.
AB  - Eight Holstein (189 +/- 57 DIM) and 4 Brown Swiss (126 +/- 49 DIM) multiparous
      cows were used in a replicated 4 x 4 Latin square with 28-d periods to determine
      the minimal dietary concentration of fish oil necessary to maximize milk
      conjugated linoleic acid (CLA) and vaccenic acid (VA). Treatments consisted of a
      control diet with a 50:50 ratio of forage to concentrate (dry matter basis), and
      3 diets with 2% added fat consisting of 0.33% fish oil, 0.67% fish oil, and 1%
      fish oil with extruded soybeans providing the balance of added fat. Dry matter
      intake (23.1, 22.6, 22.8, and 22.9 kg/d, for control, low, medium, and high fish
      oil diets, respectively) was similar for all diets. Milk production (21.5, 23.7,
      22.7, and 24.2 kg/d) was higher for cows fed the fat-supplemented diets vs. the
      control. Milk fat (4.42, 3.81, 3.80, and 4.03%) and true protein (3.71, 3.58,
      3.54, and 3.55%) concentrations decreased when cows were fed diets containing
      supplemental fat. Concentration of milk cis-9,trans-11 CLA (0.55, 1.17, 1.03, and
      1.19 g/100 g of fatty acids) was increased similarly by all diets containing
      supplemental fat. Milk VA (1.12, 2.47, 2.13, and 2.63 g/100 g of fatty acids) was
      increased most in milk from cows fed the low and high fish oil diets. Milk total
      n-3 fatty acids were increased (0.82, 0.96, 0.92, and 1.01 g/100 g of fatty
      acids) by all fat-supplemented diets. The low fish oil diet was as effective at
      increasing VA and CLA in milk as the high fish oil diet, showing that only low
      concentrations of dietary fish oil are necessary for increasing concentrations of
      VA and CLA in milk.

PMID- 16960074
TI  - Relationships among manure nitrogen output and dietary and animal factors in
      lactating dairy cows.
AB  - A large data set derived from total diet digestibility assessments on lactating
      dairy cows (535 Holstein-Friesian and 29 Norwegian) was used to examine effects
      of dietary and animal factors on manure (feces and urine) nitrogen (N) output and
      to develop mitigation strategies and prediction equations for manure N output in
      lactating dairy cows. Manure N output was positively and significantly related to
      live weight, milk yield, dietary crude protein (CP) concentration, dry matter
      intake, and N intake. Reducing the dietary CP concentration or increasing the
      milk yield decreased manure N output per kilogram of milk yield. Prediction
      equations for manure N output using live weight and milk yield, either alone or
      combined, had relatively low R2 (0.227 to 0.474) and large standard error (70.6
      to 85.6) values. Addition of dietary CP concentration to these relationships
      considerably increased R2 to 0.754 and reduced the standard error to 48.2.
      Relating manure N output to N intake produced a very high r2 (0.901) and a very
      low standard error (30.6). The addition of live weight and milk yield to this
      relationship as supporting predictors only marginally increased R2 to 0.910 and
      reduced the standard error to 29.3. The internal validation of these equations
      revealed that use of N intake as the primary predictor produced a very accurate
      prediction of manure N output. In situations in which data on N intake are not
      available, prediction equations based on dietary CP concentration, live weight,
      and milk yield together can produce a relatively accurate assessment of manure N
      output.

PMID- 16960075
TI  - An evaluation of two indirect methods of estimating body weight in Holstein
      calves and heifers.
AB  - Monitoring the growth of replacement heifers is a useful management tool to
      assist producers in achieving a reasonable goal for age at first calving.
      Standard growth curves have been established, and heart girth tapes are widely
      available to estimate body weight (BW). Probably the easiest, and undoubtedly the
      most accurate, means of determining the actual BW of heifers is by using a
      calibrated electronic scale. However, if an electronic scale is not available,
      indirect methods of BW estimation are required. The hipometer is a new indirect
      tool that uses the external width between the greater trochanters of the left and
      right femurs to estimate BW. The purpose of this observational study was to
      evaluate the hipometer and the heart girth tape to estimate the BW of Holstein
      heifers, as compared with their actual weight recorded by an electronic scale. A
      total of 311 Holstein heifers in 4 research herds, ranging in age from 1 wk old
      to immediately prior to calving (24 mo), were used in this comparison. The mean
      BW of all heifers was 261 +/- 124 kg. The Pearson values of the correlation
      between the scale and hipometer weights, and the scale and tape weights were 0.92
      and 0.94, respectively. The concordance correlations of scale weight with
      hipometer and tape weights were 0.98 and 0.99, respectively. The agreement among
      the 3 methods, as assessed by the kappa statistic, was substantial for heifers
      aged 3 to 15 mo. However, poor to no agreement was observed in heifers younger
      than 3 mo, as well as at 15 mo of age or greater (kappa 0 to 0.18). This is of
      particular concern because these groups represent the age when dairy heifers
      would be weaned (< 3 mo) and the age when breeding would normally commence (> 15
      mo). We concluded that the hipometer is an easy and useful alternative method of
      estimating the BW of Holstein heifers, particularly in heifers aged 3 to 15 mo.

PMID- 16960076
TI  - The effects of Lactobacillus buchneri 40788 and Pediococcus pentosaceus R1094 on
      the fermentation of corn silage.
AB  - The effect of inoculating whole-plant corn at the time of harvest with
      Lactobacillus buchneri 40788 (4 x 10(5) cfu/g of fresh forage) combined with
      Pediococcus pentosaceus R1094 (1 x 10(5) cfu/g) on the fermentation and aerobic
      stability of corn silage (37% dry matter) through 361 d of ensiling was
      investigated. Dry matter recovery was similar between treatments throughout the
      study except at one early time point (14 d), when treated silage had a lower
      recovery than untreated silage. The concentration of lactic acid was unaffected
      by inoculation but inoculated silages had greater concentrations of 1,2
      propanediol and acetic acid from 56 to 361 d of storage. In general, inoculation
      decreased the concentration of water-soluble carbohydrates but increased the
      concentration of ethanol. The numbers of yeasts was lower in inoculated silage at
      42, 56, 70, and 282 d of ensiling. However, inoculation did not consistently
      improve the aerobic stability of silage, suggesting that microbes other than
      yeasts may have been responsible for aerobic instability in this study. Even
      after prolonged storage (361 d), silage treated with L. buchneri 40788 and P.
      pentosaceus R1094 had normal silage fermentation characteristics.

PMID- 16960077
TI  - A meta-analysis of the effects of Lactobacillus buchneri on the fermentation and
      aerobic stability of corn and grass and small-grain silages.
AB  - The results of adding Lactobacillus buchneri to silages from 43 experiments in 23
      sources reporting standard errors were summarized using meta-analysis. The
      effects of inoculation were summarized by type of crop (corn or grass and small
      grains) and the treatments were classified into the following categories: 1)
      untreated silage with nothing applied (LB0), 2) silage treated with L. buchneri
      at < or = 100,000 cfu/g of fresh forage (LB1), and 3) silage treated with L.
      buchneri at > 100,000 cfu/g (LB2). In both types of crops, inoculation with L.
      buchneri decreased concentrations of lactic acid, and this response was dose
      dependent in corn but not in grass and small-grain silages. Treatment with L.
      buchneri markedly increased the concentrations of acetic acid in both crops in a
      dose-dependent manner. The numbers of yeasts were lower in silages treated with
      LB1 and further decreased in silages treated with LB2 compared with untreated
      silages. Untreated corn silage spoiled after 25 h of exposure to air but corn
      silage treated with LB1 did not spoil until 35 h, and this stability was further
      enhanced to 503 h with LB2. In grass and small-grain silages, yeasts were nearly
      undetectable; however, inoculation improved aerobic stability in a dose-dependent
      manner (206, 226, and 245 h for LB0, LB1, and LB2, respectively). The recovery of
      DM after ensiling was lower for LB2 (94.5%) when compared with LB0 (95.5%) in
      corn silage and was lower for both LB1 (94.8%) and LB2 (95.3%) when compared with
      LB0 (96.6%) in grass and small-grain silages.

PMID- 16960078
TI  - Calf respiratory disease and pen microenvironments in naturally ventilated calf
      barns in winter.
AB  - Relationships between air quality, a variety of environmental risk factors, and
      calf respiratory health were studied in 13 naturally ventilated calf barns during
      winter. A minimum of 12 preweaned calves were randomly selected and scored for
      the presence of respiratory disease in each barn. An air sampling device was used
      to determine airborne bacteria colony-forming units per cubic meter (cfu/m3) of
      air in calf pens and central alleys within the barns. Airborne bacteria samples
      were collected on sheep blood agar (BAP) and eosin methylene blue (EMB) agar
      plates. Temperature and relative humidity were recorded in each calf pen, the
      barn alley, and outside the barn. Samples of bedding were collected in each pen
      and DM was measured. Pen bedding type and a calf nesting score (degree to which
      the calves could nestle into the bedding) was assigned to each barn. Calf
      numbers, barn and pen dimensions, ridge, eave, and curtain openings, and exterior
      wind speed and direction were determined and used to estimate building
      ventilation rates. Factors that were significantly associated with a reduced
      prevalence of respiratory disease were reduced pen bacterial counts (log10
      cfu/m3) on BAP, presence of a solid barrier between each calf pen, and increased
      ability to nest. Individual calf pen bacterial counts were significantly
      different from barn alley bacterial counts on both BAP and EMB. Significant
      factors associated with reduced calf pen bacterial counts on BAP were increasing
      pen area, increasing number of open planes of the calf pen, decreasing pen
      temperature, and wood-particle bedding. Significant factors associated with
      reduced alley bacterial counts on BAP were increased ventilation changes per
      hour, increased barn volume per kilogram of calf, reduced pen bacterial counts,
      and barn type.

PMID- 16960079
TI  - Influence of grass-based diets on milk fatty acid composition and milk lipolytic
      system in Tarentaise and Montbeliarde cow breeds.
AB  - Two experiments were conducted to evaluate the effects of nature of forage on
      fatty acid composition and lipolytic system in cow milk to increase the
      nutritional quality of dairy products. Each experiment was divided into a 4-wk
      preexperimental and 6- or 8-wk experimental period. During the 2 preexperimental
      periods, 56 midlactating Montbeliarde or Tarentaise cows received a diet based on
      corn silage. Subsequently, in Experiment 1,40 cows were allocated into 5 groups
      (4 Montbeliarde and 4 Tarentaise cows per group) and assigned to dietary
      treatments: corn silage (87% of dry matter intake), grass silage (86%), ryegrass
      hay (90%), mountain natural grassland hay (87%), or a diet rich in concentrate
      (CONC, 65/35% concentrate/hay). In Experiment 2, 16 cows divided into 2 groups
      were fed during 3 or 6 wk mountain natural pasture (100%) or mountain natural
      grassland hay (87%). Principal component analysis was applied to describe the
      relationships among dairy performances, milk fatty acids (FA), and lipolytic
      system. The milk 18:0, cis-9-18:1, trans-11-18:1, and cis-9, trans-11-18:2
      percentages were closely associated with 3-wk mountain natural pasture diet,
      whereas short- and medium-chain (mostly saturated) FA were associated with the
      CONC diet. Tarentaise milk fat contained a lower proportion (-3 to 4 g/100 g) of
      16:0 and higher proportions of stearic acid and fewer markedly polyunsaturated FA
      than Montbeliarde milk fat. Milk lipolysis was lowest for CONC and corn silage
      groups. Milk from Tarentaise cows presented lower initial free FA and postmilking
      lipolysis. Diets given to cows, especially young grass, modified the milk content
      of FA with a putative nutritional effect on human health.

PMID- 16960080
TI  - Genetic analysis of number of mastitis cases and number of services to conception
      using a censored threshold model.
AB  - The objective of this study was to infer genetic parameters and genetic change
      for number of clinical mastitis cases (NCM) and number of services to conception
      (STC) in first-lactation Norwegian Red (NRF) cows. Records on 620,492 daughters
      of 3,064 NRF sires, with first calving from 1980 through 2004, were analyzed with
      a bivariate threshold liability model that takes censoring into account.
      Posterior mean (SD) of heritability of liability was 0.08 (0.004) for NCM and
      0.03 (0.002) for STC. The mean (SD) of the posterior distribution of the genetic
      correlation between the 2 traits was 0.21 (0.04). Posterior means of the
      correlation between herd-5-yr effects, and between residuals for NCM and STC were
      0.17 and 0.05, respectively. To evaluate effects of taking censoring into
      account, the data were also analyzed with a bivariate ordered threshold model
      ignoring censoring. The genetic correlation between NCM and STC was lower than in
      the censored threshold model (0.09 vs. 0.21). Heritability of liability to NCM
      and STC from this model was also slightly lower, whereas the point estimates of
      herd-5-yr and residual correlations were 0.15, and -0.01, respectively. These
      results suggest that genetic (co)variance may be understated in models ignoring
      censoring. For comparison purposes, the data were analyzed with a bivariate
      linear sire model and standard REML-BLUP procedures. The correlation (rank
      correlation) between sire evaluations from the censored threshold model and sire
      predicted transmitting abilities from the linear model was 0.90 (0.90) for NCM
      and 0.87 (0.86) for STC. The evolution of average sire posterior means by birth
      year of daughters was used to assess genetic change, and results indicated
      genetic reduction (i.e., genetic improvement) of NCM and little or no genetic
      change for STC in the NRF population.

PMID- 16960082
TI  - Development of a survival model with piecewise Weibull baselines for the analysis
      of length of productive life of Holstein cows in Japan.
AB  - A total of 100,000 records of Holstein dairy cows in Hokkaido, Japan, were used
      to study the current characteristics of their length of productive life, to build
      up a suitable model for genetic survival analysis, and to apply the piecewise
      Weibull baseline model. The data for this analysis only included records of cows
      belonging to herds in which more than 60% of cows had type score. Compared with
      other studies, the proportions of cows with only 1 or 2 calvings were low (24 and
      46%, respectively), indicating a very low culling rate in first or second parity
      in Hokkaido. The median length of productive life was about 1,250 d (3 yr and 5
      mo). Four different definitions of stages of lactation were studied. The best fit
      of the data was obtained when stages of lactation were chosen with cutpoints at
      0, 60, 250, and 350 d after calving. Whatever the definition of stages of
      lactation, the piecewise Weibull baseline model was better than a unique baseline
      model. The estimated shape Weibull parameters rho for the different parity x
      stage of lactation combinations varied greatly (1.0 to 5.0). The estimated hazard
      functions based on the piecewise Weibull baseline model were smooth and reflected
      the important changes in observed hazard within lactation. The results of this
      study are expected to contribute to the development of a genetic model for sire
      evaluation and to genetic improvement of length of productive life of Holstein
      cattle in Hokkaido, Japan.

PMID- 16960081
TI  - Genetic evaluation of mastitis in dairy cattle using linear models, threshold
      models, and survival analysis: a simulation study.
AB  - The objective was to study, by simulation, whether survival analysis results in a
      more precise genetic evaluation for mastitis in dairy cattle than cross-sectional
      linear models and threshold models by using observation periods for mastitis of 2
      lengths (the first 150 d of lactation, and the full lactation, respectively).
      True breeding values for mastitis liability on the underlying scale were
      simulated for daughters of 400 sires (average daughter group size, 60 or 150),
      and the possible event of a mastitis case within lactation for each cow was
      created. For the linear models and the threshold models, mastitis was defined as
      a binary trait within either the first 150 d of lactation or the full lactation.
      For the survival analysis, mastitis was defined as the number of days from
      calving to either the first case of mastitis (uncensored record) or to the day of
      censoring (i.e., day of culling, lactation d 150 or day of next calving; censored
      record). Cows could be culled early in lactation (within 10 d after calving) for
      calving-related reasons or later on because of infertility. The correlation
      between sire true breeding values for mastitis liability and sire predicted
      breeding values was greater when using the full lactation data (0.76) than when
      using data from the first 150 d (0.70) with an average of 150 daughters per sire.
      The corresponding results were 0.60 and 0.53, respectively, with an average of 60
      daughters per sire. Under these simulated conditions, the method used had no
      effect on accuracy. The higher accuracy of sire breeding values can be translated
      into a greater genetic gain, unless counteracted by a longer generation interval.

PMID- 16960083
TI  - Technical note: validation of internal control genes for gene expression analysis
      in bovine polymorphonuclear leukocytes.
AB  - Analysis of gene expression is becoming more important in all areas of biological
      research to evaluate gene expression during physiological and pathological
      conditions (e.g., mastitis), not the least in the field of animal research.
      Presently, real-time gene expression analysis is considered to be the method of
      choice for accurate and sensitive quantification of mRNA transcripts. Because
      comparison of gene expression levels is frequently the aim of these experiments,
      there is a critical need to validate internal control genes. When studying gene
      expression in bovine polymorphonuclear leukocytes, special attention should be
      paid to this validation, because polymorphonuclear leukocytes are subjected to
      numerous physiological influences, depending on the stage of lactation. In this
      study, 8 commonly used reference genes (ACT, GAPD, H2A, TBP, HPRT1, SDHA, YWHAZ,
      and 18S rRNA) were evaluated in bovine polymorphonuclear leukocytes. The
      transcription levels of 6 reference genes were determined using real-time PCR. By
      geometrically averaging the expression levels of these genes, SDHA, YWHAZ, and
      18S rRNA were selected as being the most stable genes for accurate normalization
      of real-time results of bovine polymorphonuclear leukocytes.

PMID- 16960084
TI  - Estimation of genetic parameters for quantitative trait loci for dairy traits in
      the French Holstein population.
AB  - A marker-assisted selection program (MAS) has been implemented in dairy cattle in
      France. The efficiency of such a selection program depends on the use of correct
      genetic parameters for the marked quantitative trait loci (QTL). Therefore, the
      objective of this study was to estimate the proportion of genetic variance
      explained by 4 QTL described in previous studies (these QTL are segregating on
      chromosomes 6, 14, 20, and 26). Genotypes for 11 markers were available for 3,974
      bulls grouped within 54 sire families of the French Holstein population
      undergoing MAS. The parameters were estimated for 4 QTL and 5 dairy traits: milk,
      fat and protein yields, and fat and protein percentages. The proportion of
      genetic variance explained by the QTL ranged from as low as 0.03 to 0.36%. Both
      lack of marker informativity and poor monitoring of QTL transmission might limit
      the accuracy of estimation. The QTL explained a larger proportion of genetic
      variance for milk composition traits. The QTL on chromosome 14 and chromosomes 6
      and 20 have their largest influence on fat and protein percentages, respectively.
      The overall proportions of genetic variance explained by the QTL were 27.0, 30.7,
      24.1, 48.2, and 33.6% for milk, fat and protein yields, and fat and protein
      percentages, respectively. These results clearly indicated that a large part of
      the genetic variance is explained by a small number of QTL and that their use in
      MAS might be beneficial for dairy cattle breeding programs.

PMID- 16960085
TI  - Udder health shows inbreeding depression in Danish Holsteins.
AB  - The purpose of this study was to estimate inbreeding depression for udder health
      using records on mastitis incidence and somatic cell count (SCC). Data were
      selected based on a pedigree completeness index so that inbreeding coefficients
      were reliable. Average inbreeding was 3.3%. The presence or absence of mastitis
      was considered in first (CM1), second (CM2), and third (CM3) lactations, and was
      recorded as a binary trait. Somatic cell count was also included and analyzed on
      the log scale. A minimum of 140,000 cows with records were included per trait.
      Linear sire models were used and (co)variance components were estimated. Linear
      and curvilinear effects of the coefficient of inbreeding were included.
      Inbreeding significantly affected all traits investigated. Three traits, CM1,
      CM3, and SCC, showed a nonlinear relationship between phenotype and inbreeding
      coefficient. A cow with 5% inbreeding compared with a cow with 2% inbreeding had
      a higher SCC and a higher incidence of mastitis. The SCC increased by 1,500
      cells/mL in first lactation and the incidence of mastitis increased by 1.08,
      0.55, and 0.98% in first, second, and third lactation, respectively. The
      corresponding reduction in net return from these traits over 3 lactations
      amounted to 11.00 US dollars under Danish production circumstances. These results
      are a step on the way to estimating the total cost of inbreeding depression to
      determine an acceptable rate of inbreeding.

PMID- 16960086
TI  - Temporal trends in bulk tank somatic cell count and total bacterial count in
      Irish dairy herds during the past decade.
AB  - The objective of this study was to document temporal trends in bulk tank somatic
      cell count (SCC) and total bacterial counts (TBC) in Irish dairy herds during the
      years 1994 to 2004. Three milk processors participated in the study, providing
      data on 2,754,270 individual bulk tank SCC and 2,056,992 individual bulk tank TBC
      records from 9,113 herds. Somatic cell counts decreased during the years 1994 to
      2000, followed by an annual increase thereafter of more than 2,000 cells/mL. A
      tendency existed for TBC to decrease over time. Across all years, bulk tank SCC
      were the lowest in April and highest in November; TBC were the lowest in May and
      highest in December. The significant seasonal pattern observed in herd SCC and
      TBC was an artifact of seasonal calving in Ireland. In general, herds selling
      more milk had lower bulk tank SCC and TBC. Herds having the highest SCC (i.e., >
      450,000 cells/mL) and the lowest SCC (i.e., < or = 150,000 cells/mL) both
      contributed substantially to the mean SCC of the milk pool collected by the milk
      processors. Derived transition matrices showed that between adjacent years, herds
      had the greatest probability of remaining in the same annual mean SCC or TBC
      category.

PMID- 16960087
TI  - Intracerebral hematoma: beyond the mass lesion.

PMID- 16960088
TI  - Acute myocardial infarction, ischemic stroke, sympathetic stress, and
      inflammation: birds of a feather.

PMID- 16960089
TI  - Humanin is a novel neuroprotective agent against stroke.
AB  - BACKGROUND AND PURPOSE: Humanin (HN) is a 24-amino acid peptide best known for
      its ability to protect neurons from damage caused by Alzheimer disease-related
      proteins. This study examines the neuroprotective effects of HNG (a potent form
      of HN) on focal cerebral ischemia/reperfusion injury in mice. METHODS: Mice
      underwent middle cerebral artery occlusion for 75 minutes followed by 24-hour
      reperfusion. Mice were pretreated with 0.1 microg HNG (intracerebroventricularly)
      30 minutes before ischemia; posttreated at 0, 2, 4, and 6 hours after ischemia;
      or pretreated with 1 microg HNG (intraperitoneally) 1 hour before ischemia.
      Neurological deficits and cerebral infarct volume were evaluated. Neuronal
      apoptosis and activated poly(ADP-ribose) polymerase expression were measured by
      TUNEL and Western blot analysis, respectively. Activated ERKs were examined by
      Western blot analysis. RESULTS: Pretreatment with 0.1 microg HNG
      (intracerebroventricularly) 30 minutes before ischemia reduced cerebral infarct
      volume from 56.2+/-3.0% to 26.1+/-1.4% (P<0.01). HNG posttreatment after 4 hours
      of reperfusion reduced cerebral infarct volume to 45.6+/-2.6% (P<0.05).
      Pretreatment with 1 microg HNG (intraperitoneally) 1 hour before ischemia or
      posttreatment after 2 hours of reperfusion reduced cerebral infarct volume
      significantly. HNG also significantly improved neurological function and
      inhibited both neuronal apoptosis as well as poly(ADP-ribose) polymerase
      activation. A significant decrease of phospho-ERK was observed in mice treated
      with HNG, whereas phospho-JNK and phospho-p38 levels were not altered.
      CONCLUSIONS: Our results demonstrate that HNG protects against cerebral
      ischemia/reperfusion injury in mice. HNG offers neuroprotection in vivo at least
      in part by inhibiting ERK activation. These findings suggest a potential
      therapeutic role for HNG in the treatment of stroke.

PMID- 16960090
TI  - Safety, feasibility, and short-term follow-up of drug-eluting stent placement in
      the intracranial and extracranial circulation.
AB  - BACKGROUND AND PURPOSE: The use of bare metal stents to treat symptomatic
      intracranial stenosis may be associated with significant restenosis rates. The
      advent of drug-eluting stents (DESs) in the coronary circulation has resulted in
      a reduction of restenosis rates. We report our technical success rate and short
      term restenosis rates after stenting with DESs in the intracranial and
      extracranial circulation. METHODS: This study was a retrospective review of the
      period between April 1, 2004, and April 15, 2006, of 59 patients with 62
      symptomatic intracranial or extracranial atherosclerotic lesions at 2 medical
      centers (University of Pittsburgh and Borgess Medical Center). RESULTS: The mean
      age of our cohort was 61+/-12 years. The location of the 62 lesions was as
      follows: extracranial vertebral artery 31 (50%), intracranial vertebral artery or
      basilar artery 18 (29%), extracranial internal carotid artery (ICA) near the
      petrous bone 5 (8%), and intracranial ICA 8 (13%). There were 2 (3%)
      periprocedural complications: 1 non-flow-limiting dissection and 1 disabling
      stroke. Fifty vessels were available for follow-up angiography or computed
      tomography angiography at a median time of 4.0+/-2 months. A total of 2 of 36
      extracranial stents (7%) and 1 of 26 intracranial stents (5%) were found to have
      restenosis > or = 50% at follow-up. CONCLUSIONS: This report demonstrates that
      DES delivery in the intracranial and extracranial circulation is technically
      feasible. A small percentage of patients developed short-term in-stent
      restenosis. Longer-term follow-up is required in the setting of a prospective
      study to determine the late restenosis rates for DESs in comparison with bare
      metal stents.

PMID- 16960091
TI  - Association of serial biochemical markers with acute ischemic stroke: the
      National Institute of Neurological Disorders and Stroke recombinant tissue
      plasminogen activator Stroke Study.
AB  - BACKGROUND AND PURPOSE: Biochemical markers of acute neuronal injury may aid in
      the diagnosis and management of acute ischemic stroke. Serum samples from the
      National Institute for Neurological Disorders and Stroke (NINDS) recombinant
      tissue plasminogen activator Stroke Study were analyzed for the presence of 4
      biochemical markers of neuronal, glial, and endothelial cell injury. These
      biochemical markers, myelin basic protein (MBP), neuron-specific enolase (NSE),
      S100beta, and soluble thrombomodulin, were studied for an association with
      initial stroke severity, infarct volume, and functional outcome. METHODS: In the
      original NINDS study, serum samples were drawn from all patients on presentation
      to the Emergency Department and at approximately 2 and 24 hours after initiation
      of study therapy. In this analysis, stored serum samples were available for 359
      patients; 107 patients had samples for all 3 time points. Serum marker
      concentrations were measured by ELISA techniques. We examined the relation
      between serum concentrations of each marker and the degree of baseline
      neurological deficit, functional outcome, and infarct size on computed tomography
      at 24 hours and the effect of fibrinolytic therapy. RESULTS: Higher 24-hour peak
      concentrations of MBP, NSE, and S100beta were associated with higher National
      Institutes of Health Stroke Scale baseline scores (r=0.186, P<0.0001; r=0.117,
      P=0.032; and r=0.263, P<0.0001, respectively). Higher peak concentrations of MBP
      and S100beta (r=0.209, P<0.0001; r=0.239, P<0.0001) were associated with larger
      computed tomography lesion volumes. Patients with favorable outcomes had smaller
      changes in MBP and S100beta (P<0.05) concentrations in the first 24 hours.
      Soluble thrombomodulin was not associated with any severity or outcome measure.
      CONCLUSIONS: This study corroborates previous work demonstrating correlations of
      MBP, NSE, and S100beta with clinical and radiographic features in acute stroke.
      Despite significantly better outcomes in the tissue plasminogen activator-treated
      group, we found no difference in the early release of the 4 biomarkers between
      treatment groups. Further study will define the role of biomarkers in acute
      stroke management and prognostication.

PMID- 16960092
TI  - Development and implementation of evidence-based indicators for measuring quality
      of acute stroke care: the Quality Indicator Board of the German Stroke Registers
      Study Group (ADSR).
AB  - BACKGROUND AND PURPOSE: There is no consensus about indicators for measuring
      quality of acute stroke care in Germany. Therefore, a standardized process was
      initiated recently to develop and implement evidence-based indicators for the
      measurement of quality of acute hospital stroke care. METHODS: Quality indicators
      were developed by a multidisciplinary board between November 2003 and December
      2005. The process was initiated by the German Stroke Registers Study Group in
      cooperation with the German Stroke Society, the German Society of Neurology, the
      German Stroke Foundation, Regional Offices for Quality Assurance and other
      experts proven in the field. National and international recommendations were
      considered during the development process. The process was based on a systematic
      literature review, an independent external evaluation of the process and its
      results, and a prospective pilot study to evaluate the defined indicators in
      clinical practice. RESULTS: Overall a set of 24 indicators was developed to
      measure performance of acute care hospitals in the 3 health care dimensions
      structure, process and outcome as well as in 3 treatment phases prehospital, in
      hospital/acute and postacute. Practicability of the derived indicators was tested
      in a prospective pilot study. During a 2-month period, 1006 patients in 13
      hospitals were documented. Application of the new indicator set was found to be
      feasible by participating physicians and hospitals. Median time to document the
      required information for 1 patient was 5 minutes. Nationwide implementation of
      the new indicator set within regional registers in Germany started since April
      2006. CONCLUSIONS: The development of indicators to measure hospital performance
      in stroke care is an important step toward improving stroke care on a national
      level. The chosen standardized evidence-based approach ensures maximal
      transparency, acceptance and sustainability of the developed indicators in
      Germany.

PMID- 16960093
TI  - Reduced pretreatment ipsilateral middle cerebral artery cerebral blood flow is
      predictive of symptomatic hemorrhage post-intra-arterial thrombolysis in patients
      with middle cerebral artery occlusion.
AB  - BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) can be a devastating
      complication associated with thrombolytic therapy for acute ischemic stroke. We
      hypothesized that patients with lower prethrombolysis cerebral blood flow (CBF)
      were at a higher risk of symptomatic ICH (sICH). METHODS: Twenty-three patients
      who underwent quantitative CBF assessment with Xenon CT studies for acute stroke
      before intra-arterial (IA) thrombolysis for a middle cerebral artery (MCA) or
      internal carotid artery terminus occlusion within 6 hours of symptom onset were
      studied. Univariate and multivariate analysis were carried out to determine
      predictors of sICH post-IA thrombolysis. Receiver operating characteristic curves
      were generated to determine the association between mean ipsilateral CBF and the
      occurrence of sICH. RESULTS: The mean age of our cohort was 68+/-12 years and a
      mean National Institutes of Health Stroke Scale (NIHSS) score of 18+/-3. In
      univariate analysis, patients with higher percent of core infarct, hyperglycemia,
      and reduced mean ipsilateral CBF were at risk of sICH. In multivariate analysis
      only mean ipsilateral CBF was associated with higher rates of sICH (odds ratio
      1.58; 95% CI, 1.01 to 2.51; P<0.04). The area under the receiver operating
      characteristic curve was 0.87 (95% CI, 0.76 to 0.97; P<0.005). CONCLUSIONS:
      Patients with lower pre-IA thrombolysis mean ipsilateral MCA CBF are at
      significantly higher risk for sICH in the setting of a MCA or carotid terminus
      occlusion. The threshold identified in this study may be useful for selection of
      patients with acute MCA occlusions for acute stroke thrombolysis.

PMID- 16960094
TI  - Perihematomal mitochondrial dysfunction after intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: Recent measurements in intracerebral hemorrhage (ICH)
      patients suggest a primary reduction in brain metabolism is responsible for
      reduced cerebral blood flow and low oxygen extraction surrounding the hematoma.
      We sought to determine whether reduced mitochondrial respiratory function could
      account for reduced metabolic demand in ICH patients. METHODS: Brain-tissue
      samples from 6 patients with acute spontaneous ICH and 6 control patients
      undergoing brain resection for management of seizure were evaluated. Only tissue
      removed from the brain adjacent to the hematoma was studied. Specimens were
      collected in the operating room; mitochondrial studies were begun within 1-hour.
      Mitochondrial oxygen consumption was measured after the addition of pyruvate,
      malate, and ADP, followed by oligomycin and carbonylcyanide. RESULTS: The ICH
      patients ranged in age from 40 to 54 years; 2 were female and half black.
      Hemorrhages were located in the temporal lobe (3), cerebellum (2) and parietal
      lobe (1). The average State 3 (active) O2 consumption for mitochondria from ICH
      patients was approximately 40% lower than that of control patients ( CONTROLS:
      129+/-39 versus ICH: 76+/-28 nmol O2/min per mg protein). With increasing time
      from hemorrhage to testing there was a progressive decline in State 3
      respiration. Reduced State 3 respiration was evident even at 6 hours, whereas at
      72 hours, there was essentially no O2 consumption. CONCLUSIONS: These data
      support the hypothesis that mitochondrial dysfunction and not ischemia is
      responsible for reduced oxygen metabolism in ICH. They point to a new direction
      for investigation and development of therapeutic interventions for ICH patients.

PMID- 16960095
TI  - Early coronary revascularization diminishes the risk of ischemic stroke with
      acute myocardial infarction.
AB  - BACKGROUND AND PURPOSE: Ischemic stroke is an uncommon but devastating
      complication of myocardial infarction (MI). It is possible that delay in the
      acute revascularization of these patients influences the risk of peri-MI ischemic
      stroke independent of size of infarction or residual ventricular function. The
      influence of the timing and type of revascularization on risk of ischemic stroke
      in the patient with MI has not previously been assessed. METHODS: We used the
      National Registry of Myocardial Infarction 3 and 4 databases to identify 45,997
      subjects who received thrombolytic therapy and 47,876 patients who were treated
      with primary percutaneous transluminal coronary angioplasty for MI. In-hospital
      ischemic stroke occurred in 248 (0.54%) and 150 (0.31%) patients in the two
      groups, respectively. Patients were stratified based on time from presentation to
      initial therapy. RESULTS: A statistically significant linear relationship between
      time to revascularization therapy and risk of in-hospital ischemic stroke was
      seen on univariate analysis. A multivariate model incorporating 26 other
      variables showed thrombolytic therapy within 15 minutes was associated with a
      lower risk of ischemic stroke (odds ratio, 0.58; 95% CI, 0.36-0.94). Primary
      angioplasty within 90 minutes of arrival was associated with a nonsignificant
      trend toward lower stroke risk (odds ratio, 0.68; 95% CI, 0.41-1.12).
      Interestingly, his benefit of early reperfusion therapy did not appear to be
      related to improvements in left ventricular function. CONCLUSIONS: Risk of in
      hospital ischemic stroke with MI is closely tied to the time to revascularization
      with both thrombolytic and percutaneous transluminal coronary angioplasty
      therapies. Early revascularization is independently predictive of a lower risk of
      ischemic stroke, but the mechanism of this does not appear to be related to
      improved cardiac function. The records of 45,997 subjects who received
      thrombolytic therapy and 47,876 patients who were treated with primary
      percutaneous transluminal coronary angioplasty for myocardial infarction were
      analyzed to determine the relationship between time to revascularization and the
      occurrence of ischemic stroke. A statistically significant linear relationship
      between time to revascularization therapy and risk of in-hospital ischemic stroke
      was seen on univariate analysis. A multivariate model incorporating 26 other
      variables showed thrombolytic therapy within 15 minutes of presentation was
      associated with a lower risk of ischemic stroke, and angioplasty within 90
      minutes was similarly associated with a nonsignificant trend toward lower stroke
      risk.

PMID- 16960096
TI  - Vertebral artery dissection: presenting findings and predictors of outcome.
AB  - BACKGROUND AND PURPOSE: Few data exist about clinical, radiologic findings,
      clinical outcome, and its predictors in patients with spontaneous vertebral
      artery dissection (sVAD). METHODS: Clinical characteristics, imaging findings, 3
      month outcomes, and its predictors were investigated in consecutive patients with
      sVAD. RESULTS: One hundred sixty-nine patients with 195 sVAD were identified.
      Brain ischemia occurred in 131 patients (77%; ischemic stroke, n=114, 67%;
      transient ischemic attack, n=17, 10%). Three patients with ischemic stroke showed
      also signs of subarachnoid hemorrhage (SAH); 3 (2%) had SAH without ischemia. The
      134 patients with brain ischemia or SAH had head and/or neck pain in 118 (88%)
      and pulsatile tinnitus in seven (5%) patients. The remaining 35 patients (21%)
      had isolated head and/or neck pain in 21 (12%) cases, asymptomatic sVAD in 13
      (8%), and cervical radiculopathy in one case (1%). Location of sVAD was more
      often in the pars transversaria (V2; 35%) or atlas loop (V3; 34%) than in the
      prevertebral (V1; 20%) or intracranial (V4; 11%) segment (P=0.0001). Outcome was
      favorable (modified Rankin scale score 0 or 1) in 88 (82%) of 107 ischemic stroke
      patients with follow up. Two (2%) patients died. Low baseline National Institutes
      of Health Stroke Scale score (P<0.0001) and younger age (P=0.007) were
      independent predictors of favorable outcome. CONCLUSIONS: sVAD is predominantly
      located in the pars transversaria (V2) or the atlas loop (V3). Most patients show
      posterior circulation ischemia. Favorable outcome is observed in most ischemic
      strokes and independently predicted by low National Institutes of Health Stroke
      Scale score and younger age.

PMID- 16960097
TI  - Mitochondrial PKC epsilon and mitochondrial ATP-sensitive K+ channel copurify and
      coreconstitute to form a functioning signaling module in proteoliposomes.
AB  - Mitochondria are key mediators of the cardioprotective signal and the
      mitochondrial ATP-sensitive K+ channel (mitoK(ATP)) plays a crucial role in
      originating and transmitting that signal. Recently, protein kinase C epsilon (PKC
      epsilon) has been identified as a component of the mitoK(ATP) signaling cascade.
      We hypothesized that PKC epsilon and mitoK(ATP) interact directly to form
      functional signaling modules in the inner mitochondria membrane. To examine this
      possibility, we studied K+ flux in liposomes containing partially purified
      mitoK(ATP). The reconstituted proteins were obtained after detergent extraction
      of isolated mitochondria, 200-fold purification by ion exchange chromatography,
      and reconstitution into lipid vesicles. Immunoblot analysis revealed the presence
      of PKC epsilon in the reconstitutively active fraction. Addition of the PKC
      activators 12-phorbol 13-myristate acetate, hydrogen peroxide, and the specific
      PKC epsilon peptide agonist, psi epsilonRACK, each activated mitoK(ATP)-dependent
      K+ flux in the reconstituted system. This effect of PKC epsilon was prevented by
      chelerythrine, by the specific PKC epsilon peptide antagonist, epsilonV(1-2), and
      by the specific mitoK(ATP) inhibitor 5-hydroxydecanoate. In addition, the
      activating effect of PKC agonists was reversed by exogenous protein phosphatase
      2A. These results demonstrate persistent, functional association of mitochondrial
      PKC epsilon and mitoK(ATP).

PMID- 16960098
TI  - Supportive interaction between cell survival signaling and angiocompetent factors
      enhances donor cell survival and promotes angiomyogenesis for cardiac repair.
AB  - Akt is a major cell survival and angiogenic mediator downstream of angiopoietin-1
      (Ang-1)/Tie-2 signaling pathway. We hypothesize that transplantation of
      mesenchymal stem cells (MSCs) co-overexpressing Ang-1 and Akt lead to better
      prognosis. Ang-1 and Akt genes were adenovirally transduced into MSCs from male
      Fischer rats. Cytoprotective effects of transgene overexpression in vitro were
      assessed by exposure of cells to 8 hours of anoxia. TUNEL and measurement of
      lactate dehydrogenase showed that MSCs co-overexpressing Ang-1 and Akt (MAAs)
      were more resistant to anoxia as compared with the nontransduced MSCs or those
      transduced with Ang-1 or Akt alone. For in vivo studies, after permanent coronary
      artery occlusion, animals were grouped (n=20/group) to receive intramyocardial
      injections of 70 microL of basal medium without cells (group 1) or containing
      3x10(6) nontransduced MSCs (group 2) or MAAs (group 3). Four animals per group
      were euthanized on 4, 7, and 14 days after cell transplantation for molecular
      studies. Extensive survival of MAAs was observed in group 3, which continued to
      co-overexpress transgenes in rat heart at 2 weeks after cell transplantation.
      Immunohistology at 4 weeks revealed myogenic differentiation of donor cells at
      the site of cell graft. Blood vessel density was highest in the infarct and
      periinfarct regions in group 3 (P<0.05). Echocardiography at 4 weeks showed that
      heart function indices were significantly improved in group 3 (P<0.05), including
      ejection fraction and fractional shortening as compared with groups 1 and 2. We
      conclude that supportive interaction between Ang-1 and Akt during MSC
      transplantation gave better prognosis via enhanced cell survival, improved
      angiomyogenesis, and restored global cardiac function.

PMID- 16960099
TI  - Sustained elevation of serum cortisol level causes sensitization of coronary
      vasoconstricting responses in pigs in vivo: a possible link between stress and
      coronary vasospasm.
AB  - Vasospastic angina is induced by stress, for which cortisol secreted by activated
      hypothalamic/pituitary/adrenal axis may play an important role. However, direct
      evidence for this notion is still lacking. In this study, we examined whether
      sustained elevation of serum cortisol level sensitizes coronary vasoconstricting
      responses in pigs in vivo and, if so, whether Rho-kinase, which we found is a key
      molecule of coronary vasospasm, is involved. Oral administration of cortisol (20
      mg/kg per day) increased its serum level to that seen in restraint stress in
      pigs. Thus, we examined coronary vasomotor responses in the following 4 groups:
      (1) control (without cortisol); (2) cortisol (20 mg/kg per day, p.o.) for 9 days;
      (3) cortisol plus RU38486 (a glucocorticoids receptor antagonist, 10 mg/kg per
      day, p.o.) for 9 days; and (4) cortisol for 9 days followed by 6-week withdrawal.
      Coronary angiography showed that intracoronary serotonin caused coronary
      hyperconstriction and reduction in coronary blood flow associated with ischemic
      ECG changes (coronary vasospasm) in only the cortisol group. All of these
      responses were abolished by hydroxyfasudil, a specific Rho-kinase inhibitor, in
      vivo. Organ chamber experiments demonstrated that serotonin concentration
      dependently caused hypercontractions of coronary vascular smooth muscle
      associated with Rho-kinase activation (as evidenced by the enhanced
      phosphorylation of myosin binding subunit, a substrate of Rho-kinase) in only the
      cortisol group. All of these responses were again inhibited by hydroxyfasudil in
      vitro. These results indicate that sustained elevation of serum cortisol level
      sensitizes coronary vasoconstricting responses through Rho-kinase activation,
      suggesting the link between stress and coronary vasospasm.

PMID- 16960100
TI  - Novel effect of mineralocorticoid receptor antagonism to reduce proinflammatory
      cytokines and hypothalamic activation in rats with ischemia-induced heart
      failure.
AB  - Blocking brain mineralocorticoid receptors (MRs) reduces the high circulating
      levels of tumor necrosis factor (TNF)-alpha in heart failure (HF) rats. TNF-alpha
      and other proinflammatory cytokines activate neurons in the paraventricular
      nucleus (PVN) of hypothalamus, including corticotropin-releasing hormone (CRH)
      neurons, by inducing cyclooxygenase (COX)-2 activity and synthesis of
      prostaglandin E2 by perivascular cells of the cerebral vasculature. We tested the
      hypothesis that systemic treatment with a MR antagonist would reduce hypothalamic
      COX-2 expression and PVN neuronal activation in HF rats. Rats underwent coronary
      ligation to induce HF, confirmed by echocardiography, or sham surgery, followed
      by 6 weeks treatment with eplerenone (30 mg/kg per day, orally) or vehicle
      (drinking water). Eplerenone-treated HF rats had lower plasma TNF-alpha,
      interleukin (IL)-1beta and IL-6, less COX-2 staining of small blood vessels
      penetrating PVN, fewer PVN neurons expressing Fra-like activity (indicating
      chronic neuronal activation), and fewer PVN neurons staining for TNF-alpha, IL
      1beta, and CRH than vehicle-treated HF rats. COX-2 and CRH protein expression in
      hypothalamus were 1.7- and 1.9-fold higher, respectively, in HF+vehicle versus
      sham+vehicle rats; these increases were attenuated (26% and 25%, respectively) in
      HF+eplerenone rats. Eplerenone-treated HF rats had less prostaglandin E2 in
      cerebrospinal fluid, lower plasma norepinephrine levels, lower left ventricular
      end-diastolic pressure, and lower right ventricle/body weight and lung/body
      weight ratios, but no improvement in left ventricular function. Treatment of HF
      rats with anticytokine agents, etanercept or pentoxifylline, produced very
      similar results. This study reveals a previously unrecognized effect of MR
      antagonism to minimize cytokine-induced central neural excitation in rats with
      HF.

PMID- 16960101
TI  - Sphingosine-1 phosphate prevents monocyte/endothelial interactions in type 1
      diabetic NOD mice through activation of the S1P1 receptor.
AB  - Monocyte recruitment and adhesion to vascular endothelium are key early events in
      atherosclerosis. We examined the role of sphingosine-1-phosphate (S1P) on
      modulating monocyte/endothelial interactions in the NOD/LtJ (NOD) mouse model of
      type 1 diabetes. Aortas from nondiabetic and diabetic NOD mice were incubated in
      the absence or presence of 100 nmol/L S1P. Fluorescently labeled monocytes were
      incubated with the aortas. Aortas from NOD diabetic mice bound 7-fold more
      monocytes than nondiabetic littermates (10+/-1 monocytes bound/field for
      nondiabetic mice vs 74+/-12 monocytes bound/field for diabetic mice, P<0.0001).
      Incubation of diabetic aortas with 100 nmol/L S1P reduced monocyte adhesion to
      endothelium by 90%. We found expression of S1P1, S1P2, and S1P3 receptors on NOD
      aortic endothelial cells. The S1P1 receptor-specific agonist SEW2871 inhibited
      monocyte adhesion to diabetic aortas. Studies in diabetic S1P3-deficient mice
      revealed that the S1P3 receptor did not play a pivotal role in this process. S1P
      reduced endothelial VCAM-1 induction in type 1 diabetic NOD mice, most likely
      through inhibition of nuclear factor kappaB translocation to the nucleus. Thus,
      S1P activation of the S1P1 receptor functions in an antiinflammatory manner in
      type 1 diabetic vascular endothelium to prevent monocyte/endothelial
      interactions. S1P may play an important role in the prevention of vascular
      complications of type 1 diabetes.

PMID- 16960102
TI  - Pacing-induced heterogeneities in intracellular Ca2+ signaling, cardiac
      alternans, and ventricular arrhythmias in intact rat heart.
AB  - Optical mapping studies have suggested that intracellular Ca2+ and T-wave
      alternans are linked through underlying alternations in Ca2+ cycling-inducing
      oscillations in action potential duration through Ca2+-sensitive conductances.
      However, these studies cannot measure single-cell behavior; therefore, the Ca2+
      cycling heterogeneities within microscopic ventricular regions are unknown. The
      goal of this study was to measure cellular activity in intact myocardium during
      rapid pacing and arrhythmias. We used single-photon laser-scanning confocal
      microscopy to measure Ca2+ signaling in individual myocytes of intact rat
      myocardium during rapid pacing and during pacing-induced ventricular arrhythmias.
      At low rates, all myocytes demonstrate Ca2+ alternans that is synchronized but
      whose magnitude varies depending on recovery kinetics of Ca2+ cycling for each
      individual myocyte. As rate increases, some cells reverse alternans phase, giving
      a dyssynchronous activation pattern, even in adjoining myocytes. Increased pacing
      rate also induces subcellular alternans where Ca2+ alternates out of phase with
      different regions within the same cell. These forms of heterogeneous Ca2+
      signaling also occurred during pacing-induced ventricular tachycardia. Our
      results demonstrate highly nonuniform Ca2+ signaling among and within individual
      myocytes in intact heart during rapid pacing and arrhythmias. Thus, certain
      pathophysiological conditions that alter Ca2+ cycling kinetics, such as heart
      failure, might promote ventricular arrhythmias by exaggerating these cellular
      heterogeneities in Ca2+ signaling.

PMID- 16960103
TI  - RhoA mediates angiotensin II-induced phospho-Ser536 nuclear factor kappaB/RelA
      subunit exchange on the interleukin-6 promoter in VSMCs.
AB  - The vasoconstrictor angiotensin II (Ang II) accelerates atherosclerosis by
      inducing vascular gene expression programs, producing monocyte recruitment, and
      vascular remodeling. In vascular smooth muscle cells (VSMCs), Ang II signaling
      activates interleukin (IL)-6 expression, a cytokine producing acute-phase
      inflammation, mediated by the transcription factor nuclear factor kappaB (NF
      kappaB). The classical NF-kappaB activation pathway involves cytoplasmic-to
      nuclear translocation of the potent RelA transactivating subunit; however,
      because nuclear RelA is present in VSMCs, the mechanism by which NF-kappaB
      activity is controlled is incompletely understood. In this study, we focus on
      early activation steps controlling RelA activation. Although Ang II only weakly
      induces approximately 1.5-fold RelA nuclear translocation, RelA is nevertheless
      required because short interfering RNA-mediated RelA knockdown inhibits inducible
      IL-6 expression. We find instead that Ang II stimulation rapidly induces RelA
      phosphorylation at serine residue 536, a critical regulatory site in its
      transactivating domain. Chromatin immunoprecipitation assays indicate no
      significant changes in total RelA binding to the native IL-6 promoter, but an
      apparent increase in fractional binding of phospho-Ser536 RelA. Inactivation of
      RhoA by treatment with Clostridium botulinum exoenzyme C3 exotoxin or expression
      of dominant negative RhoA blocks Ang II-inducible RelA Ser536 phosphorylation and
      IL-6 expression. Finally, enhanced phospho-Ser536 RelA formation in the aortae of
      rats chronically infused with Ang II was observed. Together, these data indicate
      a novel mechanism for Ang II-induced NF-kappaB activation in VSMCs, mediated by
      RhoA-induced phospho-Ser536 RelA formation, IL-6 expression, and vascular
      inflammation.

PMID- 16960104
TI  - Nonendothelial mesenchymal cell-derived MCP-1 is required for FGF-2-mediated
      therapeutic neovascularization: critical role of the inflammatory/arteriogenic
      pathway.
AB  - OBJECTIVE: Monocyte chemoattractant protein-1 (MCP-1) is a C-C chemokine that is
      known as an inflammatory/arteriogenic factor. Angiogenesis contributes to the
      inflammatory process; however, the molecular and cellular mechanisms of the links
      among the inflammatory pathway, arteriogenesis, and angiogenesis have not been
      well elucidated. METHODS AND RESULTS: Using murine models of fibroblast growth
      factor-2 (FGF-2)-mediated therapeutic neovascularization, we here show that FGF-2
      targets nonendothelial mesenchymal cells (NEMCs) enhancing both angiogenic
      (vascular endothelial growth factor [VEGF]) and arteriogenic (MCP-1) signals via
      independent signal transduction pathways. Severe hindlimb ischemia stimulated MCP
      1 expression that was strongly enhanced by FGF-2 gene transfer, and a blockade of
      MCP-1 activity via a dominant negative mutant as well as a deficiency of its
      functional receptor CCR2 resulted in the diminished recovery of blood flow
      attributable to adaptive and therapeutic neovascularization. Tumor necrosis
      factor (TNF)-alpha stimulated MCP-1 expression in all cell types tested, whereas
      FGF-2-mediated upregulation of MCP-1 was found only in NEMCs but not in others, a
      finding that was not affected by VEGF in vitro and in vivo. CONCLUSIONS: These
      results indicate that FGF-2 targets NEMCs independently, enhancing both
      angiogenic (VEGF) as well as inflammatory/arteriogenic (MCP-1) pathways.
      Therefore, MCP-1/CCR2 plays a critical role in adaptive and FGF-2-mediated
      therapeutic neovascularization.

PMID- 16960105
TI  - Lipoprotein-associated phospholipase A2 protein expression in the natural
      progression of human coronary atherosclerosis.
AB  - OBJECTIVE: Although lipoprotein-associated phospholipase A2 (Lp-PLA2) has
      received recent attention as a biomarker of inflammation and risk for acute
      coronary events, its relative expression in coronary plaque phenotypes, including
      unstable lesions, has not been established. METHODS AND RESULTS: Coronary
      segments (n=30) were prospectively collected from 25 sudden coronary death
      patients for immunolocalization of Lp-PLA2. Lesion morphologies were classified
      as pathologic intimal thickening, fibroatheromas, thin-cap fibroatheromas
      (fibrous cap thicknesses <65 microm), and rupture. The expression of Lp-PLA2 was
      detected using a specific monoclonal antibody. Apoptosis was identified by DNA
      end-labeling using terminal deoxynucleotidyl transferase (TdT). Lp-PLA2 staining
      in early plaques was absent or minimally detected. In contrast, thin-cap
      fibroatheromas and ruptured plaques showed intense Lp-PLA2 expression within
      necrotic cores and surrounding macrophages including those in the fibrous cap.
      The degree of macrophage apoptosis was greater in thin-cap fibroatheroma and
      ruptures compared with less advanced plaques with additional double labeling
      studies showing Lp-PLA2 present in apoptotic cells in regions of high macrophage
      density. CONCLUSIONS: Lp-PLA2 is strongly expressed within the necrotic core and
      surrounding macrophages of vulnerable and ruptured plaques, with relatively weak
      staining in less advanced lesions. These findings together with the association
      of Lp-PLA2 in apoptotic macrophages suggest a potential role in promoting plaque
      instability.

PMID- 16960106
TI  - Regulation of fibrinolysis by thrombin activatable fibrinolysis inhibitor, an
      unstable carboxypeptidase B that unites the pathways of coagulation and
      fibrinolysis.
AB  - The coagulation and fibrinolytic systems safeguard the patency of the vasculature
      and surrounding tissue. Cross regulation of coagulation and fibrinolysis plays an
      important role in preserving a balanced hemostatic process. Identification of
      Thrombin Activatable Fibrinolysis Inhibitor (TAFI) as an inhibitor of
      fibrinolysis and one of the main intermediates between coagulation and
      fibrinolysis, greatly improved our understanding of cross regulation of
      coagulation and fibrinolysis. As TAFI is an enzyme that is activated by thrombin
      generated by the coagulation system, its activation is sensitive to the dynamics
      of the coagulation system. Defects in coagulation, such as in thrombosis or
      hemophilia, resonate in TAFI-mediated regulation of fibrinolysis and imply that
      clinical symptoms of coagulation defects are amplified by unbalanced
      fibrinolysis. Thrombomodulin promotes the generation of both antithrombotic
      activated protein C (APC) and prothrombotic (antifibrinolytic) activated TAFI,
      illustrating the paradoxical effects of thrombomodulin on the regulation of
      coagulation and fibrinolysis. This review will discuss the role of TAFI in the
      regulation of fibrinolysis and detail its regulation of activation and its
      potential therapeutic applications in thrombotic disease and bleeding disorders.

PMID- 16960107
TI  - Probiotics stimulate production of natural antibodies in chickens.
AB  - Commensal bacteria in the intestine play an important role in the development of
      immune response. These bacteria interact with cells of the gut-associated
      lymphoid tissues (GALT). Among cells of the GALT, B-1 cells are of note. These
      cells are involved in the production of natural antibodies. In the present study,
      we determined whether manipulation of the intestinal microbiota by administration
      of probiotics, which we had previously shown to enhance specific systemic
      antibody response, could affect the development of natural antibodies in the
      intestines and sera of chickens. Our findings demonstrate that when 1-day-old
      chicks were treated with probiotics, serum and intestinal antibodies reactive to
      tetanus toxoid (TT) and Clostridium perfringens alpha-toxin in addition to
      intestinal immunoglobulin A (IgA) reactive to bovine serum albumin (BSA) were
      increased in unimmunized chickens. Moreover, IgG antibodies reactive to TT were
      increased in the intestines of probiotic-treated chickens compared to those of
      untreated controls. In serum, IgG and IgM reactive to TT and alpha-toxin were
      increased in probiotic-treated, unimmunized chickens compared to levels in
      untreated controls. However, no significant difference in serum levels of IgM or
      IgG response to BSA was observed. These results are suggestive of the induction
      of natural antibodies in probiotic-treated, unimmunized chickens. Elucidating the
      role of these antibodies in maintenance of the chicken immune system homeostasis
      and immune response to pathogens requires further investigation.

PMID- 16960108
TI  - Distinct contributions of vaccine-induced immunoglobulin G1 (IgG1) and IgG2a
      antibodies to protective immunity against influenza.
AB  - Vaccination represents the most effective form of protection against influenza
      infection. While neutralizing antibodies are typically measured as a correlate of
      vaccine-induced protective immunity against influenza, nonneutralizing antibodies
      may contribute to protection or amelioration of disease. The goal of this study
      was to dissect the individual contributions of the immunoglobulin G1 (IgG1) and
      IgG2a antibody isotypes to vaccine-induced immunity against influenza virus. To
      accomplish this, we utilized an influenza vaccine regimen that selectively
      enhanced IgG1 or IgG2a antibodies by using either DNA or viral replicon particle
      (VRP) vectors expressing influenza virus hemagglutinin (HA) (HA-DNA or HA-VRP,
      respectively). After HA-DNA vaccination, neutralizing antibodies were detected by
      both in vitro (microneutralization) and in vivo (lung viral titer) methods and
      were associated with increased IgG1 expression by enzyme-linked immunosorbent
      assay (ELISA). Vaccination with HA-VRP did not strongly stimulate either
      neutralizing or IgG1 antibodies but did induce IgG2a antibodies. Expression of
      IgG2a antibodies in this context correlated with clearance of virus and increased
      protection against lethal influenza challenge. Increased induction of both
      antibody isotypes as measured by ELISA was a better correlate for vaccine
      efficacy than neutralization alone. This study details separate but important
      roles for both IgG1 and IgG2a expression in vaccination against influenza and
      argues for the development of vaccine regimens that stimulate and measure
      expression of both antibody isotypes.

PMID- 16960109
TI  - Genetic analysis of Mycobacterium avium complex strains used for producing
      purified protein derivatives.
AB  - For over a century, purified protein derivatives (PPD) have been used to detect
      mycobacterial infections in humans and livestock. Among these, reagents to detect
      infections by Mycobacterium avium complex organisms have been produced, but the
      utility of these reagents has not been clearly established due in part to limited
      biologic and immunologic standardization. Because there is little information
      about the strains used to produce these reagents (avian PPD, intracellulare PPD,
      scrofulaceum PPD, and Johnin), we have performed genetic characterizations of
      strains used to produce these products. Sequence analysis of 16S rRNA and the
      hsp65 gene provided results concordant with species designations provided for M.
      avium, Mycobacterium intracellulare, and Mycobacterium scrofulaceum organisms.
      For M. avium strains, comparative genomic hybridization was performed on a whole
      genome DNA microarray, revealing one novel 7.9-kilobase genomic deletion in
      certain Johnin-producing strains, in addition to genomic variability inherent to
      the particular M. avium subspecies. Our findings indicate that considerable
      genomic differences exist between organisms used for reagents and the infecting
      organism being studied. These results serve as a baseline for potency studies of
      different preparations and should aid in comparative studies of newly discovered
      antigens for the diagnosis of infection and disease by M. avium complex
      organisms.

PMID- 16960110
TI  - Essential roles of monocytes in stimulating human peripheral blood mononuclear
      cells with Lactobacillus casei to produce cytokines and augment natural killer
      cell activity.
AB  - We examined the effect of a probiotic strain, Lactobacillus casei strain Shirota,
      on cytokine production and natural killer (NK) cell activity in human peripheral
      blood mononuclear cells (PBMNC). The cellular mechanisms of immunoregulation by
      L. casei strain Shirota were also investigated. L. casei strain Shirota
      stimulated PBMNC to secrete interleukin-12 (IL-12), gamma interferon (IFN-gamma),
      tumor necrosis factor alpha (TNF-alpha), and IL-10. However, depletion of
      monocytes from PBMNC eliminated the induction of these cytokines. L. casei strain
      Shirota was phagocytosed by monocytes and directly stimulated them to secrete IL
      12, TNF-alpha, and IL-10. IFN-gamma production was diminished by the addition of
      anti-IL-12 antibody to the PBMNC cultures. Purified T cells, but not NK cells,
      produced IFN-gamma effectively when stimulated with L. casei strain Shirota in
      the presence of monocytes, indicating that monocytes triggered by L. casei strain
      Shirota help T cells to produce IFN-gamma through secreting IL-12. In addition,
      NK cell activity and CD69 expression on NK cells increased after cultivation of
      PBMNC with L. casei strain Shirota. When monocytes were depleted from PBMNC, L.
      casei strain Shirota did not enhance NK cell activity. These results demonstrate
      that monocytes play critical roles in the induction of cytokines and following
      the augmentation of NK cell activity during the stimulation of human PBMNC with
      L. casei strain Shirota.

PMID- 16960111
TI  - Development and validation of a fourfold multiplexed opsonization assay (MOPA4)
      for pneumococcal antibodies.
AB  - Opsonophagocytic killing assays (OPAs) are essential for developing and improving
      pneumococcal vaccines. There is a need for a high-throughput, reliable,
      standardized, and fully characterized OPA for pneumococcal antibodies. To meet
      the need, we have developed and characterized a fourfold multiplexed OPA (MOPA4)
      against 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) of
      pneumococci. Thirteen target bacteria were made resistant to only one of the
      following antibiotics: optochin, streptomycin, spectinomycin, and trimethoprim.
      Following optimization of assay conditions, accuracy of MOPA4 was determined by
      testing 30 sera from old adults in the MOPA4 and the single-serotype assays. The
      opsonization titers obtained with both assays agreed well (r(2) > 0.95). Although
      22 (out of 390; approximately 6%) results differed more than twofold, the
      differences were not reproducible. The assay was specific: preabsorbing test sera
      with homologous polysaccharide (PS) completely abrogated opsonic activity, but a
      pool of unrelated PS (5 mug/ml of each) had no effect. Intra- and interassay
      coefficients of variation were 10 and 22%, respectively. MOPA4 results were
      unaffected by having different target pneumococcal serotypes in each assay group.
      Also, HL60 cell-to-bacteria ratios could be varied twofold without affecting the
      results. We conclude that MOPA4 is sensitive, accurate, specific, precise, and
      robust enough for large-scale clinical studies. Furthermore, MOPA4 should allow
      evaluation of multivalent pneumococcal vaccines with the limited volume of serum
      typically available from young children.

PMID- 16960112
TI  - Vaccines with the MF59 adjuvant do not stimulate antibody responses against
      squalene.
AB  - Squalene is a naturally occurring oil which has been used in the development of
      vaccine adjuvants, such as the oil-in-water emulsion MF59. In past years, by use
      of noncontrolled and nonvalidated assays, a claim was made that antisqualene
      antibodies were detectable in the sera of individuals with the so-called Gulf War
      syndrome. Using a validated enzyme-linked immunosorbent assay for the
      quantitation of immunoglobulin G (IgG) and IgM antibodies against squalene, we
      demonstrated that antisqualene antibodies are frequently detectable at very low
      titers in the sera of subjects who were never immunized with vaccines containing
      squalene. More importantly, vaccination with a subunit influenza vaccine with the
      MF59 adjuvant neither induced antisqualene antibodies nor enhanced preexisting
      antisqualene antibody titers. In conclusion, antisqualene antibodies are not
      increased by immunization with vaccines with the MF59 adjuvant. These data extend
      the safety profile of the MF59 emulsion adjuvant.

PMID- 16960113
TI  - Unique model of dormant infection for tuberculosis vaccine development.
AB  - Most individuals exposed to Mycobacterium tuberculosis become infected but hinder
      the infectious process in dormant foci, known as latent tuberculosis. This
      limited infection usually stimulates strong T-cell responses, which provide
      lifelong resistance to tuberculosis. However, latent tuberculosis is still poorly
      understood, particularly because of the lack of a reliable animal model of
      dormant infection. Here we show that inoculation of mice with a unique
      streptomycin-auxotrophic mutant of Mycobacterium tuberculosis recapitulates
      dormant infection. The mutant grows unimpaired in the presence of streptomycin
      and no longer grows but remains viable for long periods of time after substrate
      removal, shifting from the log growth phase to the latent stage, as indicated by
      augmented production of alpha-crystallin. Mice challenged with the mutant and
      inoculated with streptomycin for approximately 3 weeks developed a limited
      infection characterized by a low bacteriological burden and the presence of
      typical granulomas. After substrate withdrawal, the infection was hindered but
      few microorganisms remained viable (dormant) in the animals' tissues for at least
      6 months. In addition, the animals developed both potent T-cell responses to M.
      tuberculosis antigens, such as early culture filtrate, Ag85B, and ESAT-6, and
      resistance to reinfection with virulent M. tuberculosis. Therefore, infection of
      mice or other animals (e.g., guinea pigs) with M. tuberculosis strain 18b
      constitutes a simple and attractive animal model for evaluation of
      antituberculosis vaccines in the context of an M. tuberculosis-presensitized
      host, a prevailing condition among humans in need of a vaccine.

PMID- 16960114
TI  - Isolation of high-affinity single-chain antibodies against Mycobacterium avium
      subsp. paratuberculosis surface proteins from sheep with Johne's disease.
AB  - Johne's disease, caused by infection with Mycobacterium avium subsp.
      paratuberculosis, causes significant economic losses to the livestock farming
      industry. Improved investigative and diagnostic tools-necessary to understand
      disease processes and to identify subclinical infection-are much sought after.
      Here, we describe the production of single-chain antibodies with defined
      specificity for M. avium subsp. paratuberculosis surface proteins. Single-chain
      antibodies (scFv) were generated from sheep with Johne's disease by cloning heavy
      chain and lambda light-chain variable regions and expressing these in fusion with
      gene III of filamentous phages. Two scFv clones (designated SurfS1.2 and
      SurfS2.2) were shown to be immunoreactive against M. avium subsp.
      paratuberculosis surface targets by flow cytometry, and immunoblotting identified
      specificity for a 34-kDa proteinase-susceptible determinant. Both antibodies were
      cross-reactive against Mycobacterium avium subsp. avium but nonreactive against
      Mycobacterium bovis or Mycobacterium phlei cells and were shown to be capable of
      enriching M. avium subsp. paratuberculosis cells by a factor of approximately
      10(6)-fold when employed in magnetic bead separation of mixed Mycobacterium sp.
      cultures. Further, magnetic bead separation using SurfS1.2 and SurfS2.2 was
      capable of isolating as few as 10(3) M. avium subsp. paratuberculosis cells from
      ovine fecal samples, indicating the diagnostic potential of these reagents.
      Finally, inclusion of SurfS1.2 or SurfS2.2 in in vitro broth culture with M.
      avium subsp. paratuberculosis indicated that surface binding activity did not
      impede bacterial growth, although colony clumping was prevented. These results
      are discussed in terms of the potential use of single-chain phage display
      monoclonal antibodies as novel diagnostic reagents.

PMID- 16960115
TI  - Cattle husbandry in Ethiopia is a predominant factor affecting the pathology of
      bovine tuberculosis and gamma interferon responses to mycobacterial antigens.
AB  - Bovine tuberculosis is a major economic problem and a potential public health
      risk. Improved diagnostics like the gamma interferon (IFN-gamma) test with ESAT6
      and/or CFP10 could contribute to the control program. We assessed IFN-gamma
      responses in zebu (Ethiopian Arsi breed) and Holstein cattle kept indoors or in a
      pasture to tuberculin purified protein derivative (PPD) and an ESAT6-CFP10
      protein cocktail. Furthermore, the intensity and distribution of pathology of
      bovine tuberculosis were compared between the two breeds. Our data demonstrated
      significantly (all P < 0.02) higher IFN-gamma responses to avian PPD, bovine PPD,
      and the ESAT6-CFP10 protein cocktail in Holstein than in zebu cattle, while
      lesion severities in infected animals and tuberculin skin test responses did not
      differ significantly (P > 0.05) between the two breeds. Holstein cattle that were
      kept indoors produced significantly (all P < 0.01) higher IFN-gamma levels in
      response to avian PPD, bovine PPD, and the ESAT6-CFP10 protein cocktail than did
      Holstein cattle kept in a pasture. Moreover, lesion severity was significantly
      higher in Holstein cattle kept indoors (P = 0.001) than in those kept in the
      pasture. Lesions were localized predominantly in the digestive tract in cattle
      kept in a pasture, while they were localized in the respiratory tract in cattle
      kept indoors. In conclusion, in Holstein cattle, husbandry was a dominant factor
      influencing the severity of tuberculosis lesions and IFN-gamma responses to
      mycobacterial antigens compared to breed. A difference in the cellular immune
      response between zebu and Holstein cattle was observed, while tuberculosis lesion
      severities were identical in the two breeds, when both were kept in a pasture.

PMID- 16960117
TI  - Altered enzyme-linked immunosorbent assay immunoglobulin M (IgM)/IgG optical
      density ratios can correctly classify all primary or secondary dengue virus
      infections 1 day after the onset of symptoms, when all of the viruses can be
      isolated.
AB  - We compared dengue virus (DV) isolation rates and tested whether acute primary
      (P) and acute/probable acute secondary (S/PS) DV infections could be correctly
      classified serologically when the patients' first serum (S1) samples were
      obtained 1 to 3 days after the onset of symptoms (AOS). DV envelope/membrane
      protein-specific immunoglobulin M (IgM) capture and IgG capture enzyme-linked
      immunosorbent assay (ELISA) titrations (1/log(10) 1.7 to 1 log(10) 6.6 dilutions)
      were performed on 100 paired S1 and S2 samples from suspected DV infections. The
      serologically confirmed S/PS infections were divided into six subgroups based on
      their different IgM and IgG responses. Because of their much greater dynamic
      ranges, IgG/IgM ELISA titer ratios were more accurate and reliable than IgM/IgG
      optical density (OD) ratios recorded at a single cutoff dilution for
      discriminating between P and S/PS infections. However, 62% of these patients' S1
      samples were DV IgM and IgG titer negative (<OD(max)/2 titer threshold), and in
      35% of the S/PS infections, the patients' S1 and S2 samples were IgM titer
      negative. The IgM OD values were, however, much higher than those of IgG in the
      S1 samples of many of these, and the other, S/PS infections. This necessitated
      using higher (>or=2.60 and <2.60) discriminatory IgM/IgG OD (DOD) ratios on these
      S1 samples than those published previously to correctly classify the highest
      percentage of these P and S/PS infections. The DV isolation rate was highest
      (12/12; 100%) using IgG and IgM titer-negative S1 samples collected 1 day AOS,
      when 100% of them were correctly classified as P or S/PS infections using these
      higher DOD ratios.

PMID- 16960116
TI  - Stimulation of human monocytes with the gram-positive vaccine vector
      Streptococcus gordonii.
AB  - Streptococcus gordonii is a bacterial vaccine vector which has previously been
      shown to activate dendritic cells in vitro and to induce local and systemic
      immune responses in vivo. In the present study, human monocytes (THP-1 cell line
      and peripheral blood monocytes) were characterized following interaction with S.
      gordonii. Treatment of human monocytes with S. gordonii but not latex beads
      induced a clear up-regulation of CD83, CD40, CD80, and CD54 and the down
      regulation of CD14. Furthermore, bacterial treatment stimulated an increased
      expression of Toll-like receptor 5 (TLR5), TLR6, and TLR7, production of the
      proinflammatory cytokines tumor necrosis factor alpha and interleukin 1 beta, and
      reduction of the phagocytic activity. This work shows that the immunostimulatory
      activity of S. gordonii is not restricted to induction of dendritic-cell
      maturation but also affects the differentiation process of human monocytes.

PMID- 16960118
TI  - Phase I clinical evaluation of a synthetic oligosaccharide-protein conjugate
      vaccine against Haemophilus influenzae type b in human adult volunteers.
AB  - Since 1989, we have been involved in the development of a vaccine against
      Haemophilus influenzae type b. The new vaccine is based on the conjugation of
      synthetic oligosaccharides to tetanus toxoid. Our main goals have been (i) to
      verify the feasibility of using the synthetic antigen and (ii) to search for new
      production alternatives for this important infant vaccine. Overall, eight trials
      have already been conducted with adults, children (4 to 5 years old), and
      infants. We have described herein the details from the first two phase I clinical
      trials conducted with human adult volunteers under double blind, randomized
      conditions. The participants each received a single intramuscular injection to
      evaluate safety and initial immunogenicity. We have found an excellent safety
      profile and an antibody response similar to the one observed for the control
      vaccine.

PMID- 16960119
TI  - Immunoglobulin G, A, and M responses to BK virus in renal transplantation.
AB  - Immunoglobulin G (IgG), IgA, and IgM antibodies were measured in serum samples
      from 71 organ donors, 81 kidney transplant recipients at transplantation, and 67
      patients during the posttransplant period by using a virus-like particle-based
      enzyme-linked immunosorbent assay (ELISA). BK virus (BKV) and JC virus DNA were
      detected in urine and plasma by real-time PCR. IgG antibodies to BKV were
      demonstrated in the majority (80.3 to 100%) of patients irrespective of clinical
      category, but titers were highest in patients with active viral replication. IgA
      antibodies were present with greater frequency (72.7 to 81.3% versus 0 to 23.6%;
      P < 0.001) and higher titer (mean optical density, 0.11 to 0.15 versus 0.05 to
      0.08; P < 0.001) in patients who were BKV DNA positive than those who were BKV
      DNA negative. IgM antibodies showed a similar pattern of reactivity but lower
      frequency in the setting of active viral replication (9.1 to 43.7% versus 0 to
      1.4%; P < 0.001). A rise in IgG level of >0.577 optical density (OD) units or a
      rise in IgA or IgM level of >0.041 OD units was strongly associated with active
      viral replication. Urine viral load showed a positive correlation with IgM titer
      (r = 0.22) but a negative correlation with IgG titer (r = -0.28) and IgA titer (r
      = -0.1). Chronic dialysis patients typically did not have serologic or virologic
      evidence of active BKV infection. Anti-BKV titers did not rise in patients with
      JC viruria. In conclusion, measurement of anti-BKV antibody titer and class
      response can be used to detect the onset of viral replication. ELISAs can be
      quite specific despite considerable sequence homology between BK virus and JC
      virus.

PMID- 16960121
TI  - Sorting out the complexities of reverse cholesterol transport: CETP
      polymorphisms, HDL, and coronary disease.

PMID- 16960120
TI  - Characterization of a phenotypically unique population of CD13+ dendritic cells
      resident in the spleen.
AB  - Immature dendritic cells (DCs) resident in bovine spleens represent a distinct
      CD11a(+) CD11c(+) CD13(+) CD172(+) CD205(+) population compared to those
      circulating in peripheral blood or trafficking via afferent lymph. Upon cytokine
      induced maturation, splenic DCs both efficiently present antigen in the
      stimulation of allogeneic lymphocyte proliferation and recall antigen-specific
      responses.

PMID- 16960122
TI  - Type 2 diabetes, thiazolidinediones: bad to the bone?

PMID- 16960123
TI  - A simple twist of science: the convoluted tale of ghrelin continues.

PMID- 16960124
TI  - Mucin granule intraluminal organization.
AB  - Mucus secretions have played a central role in the evolution of multicellular
      organisms, enabling adaptation to widely differing environments. In vertebrates,
      mucus covers and protects the epithelial cells in the respiratory,
      gastrointestinal, urogenital, visual, and auditory systems, amphibian's
      epidermis, and the gills in fishes. Deregulation of mucus production and/or
      composition has important consequences for human health. For example, mucus
      obstruction of small airways is observed in chronic airway diseases, including
      chronic obstructive pulmonary disease, asthma, and cystic fibrosis. The major
      protein component in the mucus is a family of large, disulfide-bonded
      glycoproteins known as gel-forming mucins. These proteins are accumulated in
      large, regulated secretory granules (the mucin granules) that occupy most of the
      apical cytoplasm of specialized cells known as mucous/goblet cells. Since mucin
      oligomers have contour dimensions larger than the mucin granule average diameter,
      the question arises how these highly hydrophilic macromolecules are organized
      within these organelles. I review here the intraluminal organization of the mucin
      granule in view of our knowledge on the structure, biosynthesis, and biophysical
      properties of gel-forming mucins, and novel imaging studies in living
      mucous/goblet cells. The emerging concept is that the mucin granule lumen
      comprises a partially condensed matrix meshwork embedded in a fluid phase where
      proteins slowly diffuse.

PMID- 16960125
TI  - Thyroid transcription factor in differentiating type II cells: regulation,
      isoforms, and target genes.
AB  - Thyroid transcription factor-1 (TTF-1, product of the Nkx2.1 gene) is essential
      for branching morphogenesis of the lung and enhances expression of surfactant
      proteins by alveolar type II cells. We investigated expression of two TTF-1 mRNA
      transcripts, generated by alternative start sites and coding for 42- and 46-kD
      protein isoforms in the mouse, during hormone-induced differentiation of human
      fetal lung type II cells in culture. Transcript for 42-kD TTF-1 was 20-fold more
      abundant than TTF-1(46) mRNA by RT-PCR. Only 42-kD protein was detected in lung
      cells, and its content increased during in vivo development and in response to in
      vitro glucocorticoid plus cAMP treatment. To examine TTF-1 target proteins,
      recombinant, phosphorylated TTF-1(42) was expressed in nuclei of cells by
      adenovirus transduction. By microarray analysis, 14 genes were comparably induced
      by recombinant TTF-1 (rTTF-1) and hormone treatment, and 9 additional hormone
      responsive genes, including surfactant proteins-A/B/C, were partially induced by
      rTTF-1. The most highly (approximately 10-fold) TTF-1-induced genes were DC-LAMP
      (LAMP3) and CEACAM6 with induction confirmed by Western analysis and
      immunostaining. Treatment of cells with hormones plus small inhibitory RNA
      directed toward TTF-1 reduced TTF-1 content by approximately 50% and inhibited
      hormone induction of the 23 genes induced by rTTF-1. In addition, knockdown of
      TTF-1 inhibited 72 of 274 other genes induced by hormones. We conclude that 42-kD
      TTF-1 is required for induction of a subset of regulated genes during type II
      cell differentiation.

PMID- 16960126
TI  - Enhanced myofibroblastic differentiation and survival in Thy-1(-) lung
      fibroblasts.
AB  - Thy-1 is a glycosylphosphatidyl-inositol-linked cell surface glycoprotein whose
      exact biological role remains unclear. Differential expression of Thy-1 affects
      fibroblast proliferation and fibrogenic signaling. In idiopathic pulmonary
      fibrosis, the proliferating myofibroblasts within the fibroblastic foci are Thy
      1(-), whereas normal lung fibroblasts are predominantly Thy-1(+). In this study,
      we used rat lung fibroblasts sorted for Thy-1 expression to examine
      myofibroblastic differentiation in response to fibrogenic stimuli. We examined
      the effects of transforming growth factor-beta, endothelin-1, and connective
      tissue growth factor on the expression of myofibroblast proteins and myogenic
      regulatory factors by real-time RT-PCR and immunoblotting. Thy-1(-) cells have
      significantly higher myofibroblast and myogenic regulatory factor gene and
      protein expression compared with Thy-1(+) cells, confirmed by immunofluorescence.
      We also used floating collagen matrix contraction assays to assess the functional
      differentiation of the fibroblasts. At baseline and after stimulation with
      transforming growth factor-beta and endothelin-1, Thy-1(-) cells caused
      significantly greater collagen contraction than did Thy-1(+) cells, supporting
      the hypothesis that Thy-1(-) cells are more fully differentiated myofibroblasts.
      Because apoptosis has been implicated in the regression of myofibroblasts, we
      examined the percentage of apoptotic cells in the contracted collagen matrices at
      baseline and after stimulation with fibrogenic agents. A significantly greater
      proportion of Thy-1(+) cells underwent apoptosis in all conditions compared with
      Thy-1(-) fibroblasts. Transfection of Thy-1 into Thy-1(-) cells inhibits collagen
      matrix contraction and reduces cell survival. Our data indicate that Thy-1
      regulates myogenic gene expression, myofibroblastic differentiation, and survival
      in lung fibroblasts.

PMID- 16960127
TI  - Reflections on the European Union Eurythron Network Meeting "Molecular Control of
      Erythropoiesis," September 22-23, 2005, Istituto Superiore di Sanita, Rome,
      Italy.
AB  - Red blood cells (RBCs) mediate oxygen transport throughout the body, a function
      that is essential for life. RBCs are continuously produced via a process called
      erythropoiesis. Anemias (insufficient numbers of functional RBCs), caused by
      failure of erythropoiesis, are a major cause of disease worldwide. Hereditary
      anemias constitute the most common human genetic disorders; they have no
      effective cure yet. The European research training network Eurythron follows a
      multidisciplinary approach to clarify the important molecular mechanisms in
      normal and pathological erythropoiesis, with a view to develop novel therapies to
      cure the anemias. The aim is to generate a comprehensive molecular description of
      mechanisms governing specification of hematopoietic stem cells in embryogenesis,
      lineage commitment, differentiation, and postmitotic maturation of RBCs. We
      report on the Eurythron meeting in Rome, in which novel approaches in stem cell
      and erythroid cell biology, including in vitro expansion of primary cells,
      biochemistry of receptor/signal transduction complexes and transcription factors,
      and (epi)genetics, were discussed.

PMID- 16960128
TI  - Potential treatment of cerebral global ischemia with Oct-4+ umbilical cord matrix
      cells.
AB  - Potential therapeutic effects of Oct-4-positive rat umbilical cord matrix (RUCM)
      cells in treating cerebral global ischemia were evaluated using a reproducible
      model of cardiac arrest (CA) and resuscitation in rats. Animals were randomly
      assigned to four groups: A, sham-operated; B, 8-minute CA without pretreatment;
      C, 8-minute CA pretreated with defined media; and D, 8-minute CA pretreated with
      Oct-4(+) RUCM cells. Pretreatment was done 3 days before CA by 2.5-microl
      microinjection of defined media or approximately 10(4) Oct-4(+) RUCM cells in
      left thalamic nucleus, hippocampus, corpus callosum, and cortex. Damage was
      assessed histologically 7 days after CA and was quantified by the percentage of
      injured neurons in hippocampal CA1 regions. Little damage (approximately 3%-4%)
      was found in the sham group, whereas 50%-68% CA1 pyramidal neurons were injured
      in groups B and C. Pretreatment with Oct-4(+) RUCM cells significantly (p < .001)
      reduced neuronal loss to 25%-32%. Although the transplanted cells were found to
      have survived in the brain with significant migration, few were found directly in
      CA1. Therefore, transdifferentiation and fusion with host cells cannot be the
      predominant mechanisms for the observed protection. The Oct-4(+) RUCM cells might
      repair nonfocal tissue damage by an extracellular signaling mechanism. Treating
      cerebral global ischemia with umbilical cord matrix cells seems promising and
      worthy of further investigation.

PMID- 16960129
TI  - Screening for genes essential for mouse embryonic stem cell self-renewal using a
      subtractive RNA interference library.
AB  - The pluripotency of mouse embryonic stem (ES) cells is maintained by self
      renewal. To screen for genes essential for this process, we constructed an RNA
      interference (RNAi) library by inserting subtracted ES cell cDNA fragments into
      plasmid containing two opposing cytomegalovirus promoters. ES cells were
      transfected with individual RNAi plasmids and levels of the pluripotency marker
      Oct-4 were monitored 48 hours later by real time RT-PCR. Of the first 89 RNAi
      plasmids characterized, 12 downregulated Oct-4 expression to less than 50% of the
      normal level and 7 of them upregulated Oct-4 expression to more than 150% of the
      normal level. To investigate their long-term effect on self-renewal, ES cells
      were transfected by these 19 RNAi plasmids individually and G418-resistant
      colonies were subjected to alkaline phosphatase (AP) staining after 7 days
      selection. Except for 4 plasmids that caused cell death, the ratio of AP positive
      colonies was repressed to less than 60% of the control group by the other 15
      plasmids and even below 20% by 10 plasmids. The cDNA fragments in these 10
      plasmids correspond to eight genes, including Zfp42/Rex-1, which was chosen for
      further functional analysis. RNAi knockdown of Zfp42 induced ES cells
      differentiate to endoderm and mesoderm lineages, and overexpression of Zfp42 also
      caused ES cells to lose the capacity of self-renewal. Our results indicate that
      RNAi screen is a feasible and efficient approach to identify genes involved in ES
      cells self-renewal. Further functional characterization of these genes will
      promote our understanding of the complex regulatory networks in ES cells.

PMID- 16960131
TI  - Ablation of undifferentiated human embryonic stem cells: exploiting innate
      immunity against the Gal alpha1-3Galbeta1-4GlcNAc-R (alpha-Gal) epitope.
AB  - Although undifferentiated human embryonic stem cells (hESCs) are tumorigenic,
      this capacity is lost after differentiation, and hESCs are being widely
      investigated for applications in regenerative medicine. To engineer protection
      against the unintentional transplantation of undifferentiated cells, we generated
      hESCs carrying a construct in which the alpha1,3-galactosyltransferase (GalT)
      open reading frame was transcribed from the hTERT promoter (pmGT). Because the
      endogenous GalT gene is inactive, GalT expression was limited to undifferentiated
      cells. A second chimeric construct (pmfGT) differed by replacement of the GalT
      leader sequence for that of the fucosyltransferase gene. Two subclones containing
      stable integrations of pmGT and pmfGT (M2 and F11, respectively) were assessed
      for their response to human serum containing antibodies to the Galalpha1
      3Galbeta1-4GlcNAc-R (alpha-gal) epitope. The low-variegation line, M2, and to a
      lesser extent the more variegated line F11, were sensitive to human serum when
      exposed in the undifferentiated state. However, M2 cells were largely insensitive
      after differentiation and retained both a normal karyotype and the ability to
      differentiate into derivatives of the three germ layers in severe combined
      immunodeficient mice. These data exemplify a method of protection against
      residual, undifferentiated hESCs prior to engraftment and may provide ongoing
      immune surveillance after engraftment against dedifferentiation or against de
      novo tumorigenesis involving hTERT reactivation. Untransfected H9 cells were not
      sensitive to the human serum used in this study. Hence, in our system,
      interactions of hESCs with other circulating antibodies, such as anti-Neu5Gc,
      were not observed.

PMID- 16960130
TI  - Bone morphogenetic protein signaling inhibits hair follicle anagen induction by
      restricting epithelial stem/progenitor cell activation and expansion.
AB  - Epithelial stem cells (EP-SCs) located in the bulge region of a hair follicle
      (HF) have the potential to give rise to hair follicle stem/progenitor cells that
      migrate down to regenerate HFs. Bone morphogenetic protein (BMP) signaling has
      been shown to regulate the HF cycle by inhibiting anagen induction. Here we show
      that active BMP signaling functions to prevent EP-SC activation and expansion.
      Dynamic expression of Noggin, a BMP antagonist, releases EP-SCs from BMP-mediated
      restriction, leading to EP-SC activation and initiation of the anagen phase.
      Experimentally induced conditional inactivation of the BMP type IA receptor
      (Bmpr1a) in EP-SCs leads to overproduction of HF stem/progenitor cells and the
      eventual formation of matricomas. This genetic manipulation of the BMP signaling
      pathway also reveals unexpected activation of beta-catenin, a major mediator of
      Wnt signaling. We propose that BMP activity controls the HF cycle by antagonizing
      Wnt/beta-catenin activity. This is at least partially achieved by BMP-mediated
      enhancement of transforming growth factor-beta-regulated epithelial cell-specific
      phosphatase (PTEN) function. Subsequently, PTEN, through phosphatidyl inositol 3
      kinase-Akt, inhibits the activity of beta-catenin, the convergence point of the
      BMP and Wnt signaling pathways.

PMID- 16960133
TI  - Stage-specific conditional mutagenesis in mouse embryonic stem cell-derived
      neural cells and postmitotic neurons by direct delivery of biologically active
      Cre recombinase.
AB  - Conditional mutagenesis using Cre/loxP recombination is a powerful tool to
      investigate genes involved in neural development and function. However, the
      efficient delivery of biologically active Cre recombinase to neural cells,
      particularly to postmitotic neurons, represents a limiting factor. In this study,
      we devised a protocol enabling highly efficient conditional mutagenesis in ESC
      derived neural progeny. Using a stepwise in vitro differentiation paradigm, we
      demonstrate that recombinant cell-permeable Cre protein can be used to
      efficiently induce recombination at defined stages of neural differentiation.
      Recombination rates of more than 90% were achieved in multipotent pan-neural and
      glial precursors derived from the Z/EG reporter mouse ESC line, in which Cre
      recombination activates enhanced green fluorescent proteinexpression. Recombined
      precursor cells displayed a normal phenotype and were able to differentiate into
      neurons and/or glial cells, indicating that Cre treatment has no overt side
      effects on proliferation and neural differentiation. Our data further demonstrate
      that recombination via Cre protein transduction is not restricted to dividing
      cells but can even be applied to postmitotic neurons. The ability to conduct
      Cre/loxP recombination at defined stages of stem cell differentiation in an
      expression-independent manner provides new prospects for studying the role of
      individual genes under stringent temporal control.

PMID- 16960134
TI  - Ex vivo large-scale generation of human platelets from cord blood CD34+ cells.
AB  - In the present investigation, we generated platelets (PLTs) from cord blood (CB)
      CD34(+) cells using a three-phase culture system. We first cultured 500 CB
      CD34(+) cells on telomerase gene-transduced human stromal cells (hTERT stroma) in
      serum-free medium supplemented with stem cell factor (SCF), Flt-3/Flk-2 ligand
      (FL), and thrombopoietin (TPO) for 14 days. We then transferred the cells to
      hTERT stroma and cultured for another 14 days with fresh medium containing
      interleukin-11 (IL-11) in addition to the original cytokine cocktail.
      Subsequently, we cultured the cells in a liquid culture medium containing SCF,
      FL, TPO, and IL-11 for another 5 days to recover PLT fractions from the
      supernatant, which were then gel-filtered to purify the PLTs. The calculated
      yield of PLTs from 1.0 unit of CB (5 x 10(6) CD34(+) cells) was 1.26 x 10(11) -
      1.68 x 10(11) PLTs. These numbers of PLTs are equivalent to 2.5-3.4 units of
      random donor-derived PLTs or 2/5-6/10 of single-apheresis PLTs. The CB-derived
      PLTs exhibited features quite similar to those from peripheral blood in
      morphology, as revealed by electron micrographs, and in function, as revealed by
      fibrinogen/ADP aggregation, with the appearance of P-selectin and activated
      glycoprotein IIb-IIIa antigens. Thus, this culture system may be applicable for
      large-scale generation of PLTs for future clinical use.

PMID- 16960135
TI  - In vivo distribution of human adipose-derived mesenchymal stem cells in novel
      xenotransplantation models.
AB  - The potential for human adipose-derived mesenchymal stem cells (AMSC) to traffic
      into various tissue compartments was examined using three murine
      xenotransplantation models: nonobese diabetic/severe combined immunodeficient
      (NOD/SCID), nude/NOD/SCID, and NOD/SCID/MPSVII mice. Enhanced green fluorescent
      protein was introduced into purified AMSC via retroviral vectors to assist in
      identification of cells after transplantation. Transduced cells were administered
      to sublethally irradiated immune-deficient mice through i.v., intraperitoneal, or
      subcutaneous injection. Up to 75 days after transplantation, tissues were
      harvested and DNA polymerase chain reaction (PCR) was performed for specific
      vector sequences as well as for human Alu repeat sequences. Duplex quantitative
      PCR using human beta-globin and murine rapsyn primers assessed the contribution
      of human cells to each tissue. The use of the novel NOD/SCID/MPSVII mouse as a
      recipient allowed rapid identification of human cells in the murine tissues,
      using an enzyme reaction that was independent of surface protein expression or
      transduction with an exogenous transgene. For up to 75 days after
      transplantation, donor-derived cells were observed in multiple tissues,
      consistently across the various administration routes and independent of
      transduction parameters. Tissue localization studies showed that the primary MSC
      did not proliferate extensively at the sites of lodgement. We conclude that human
      AMSC represent a population of stem cells with a ubiquitous pattern of tissue
      distribution after administration. AMSC are easily obtained and highly amenable
      to current transduction protocols for retroviral transduction, making them an
      excellent avenue for cell-based therapies that involve a wide range of end tissue
      targets.

PMID- 16960136
TI  - Nitric oxide decreases subventricular zone stem cell proliferation by inhibition
      of epidermal growth factor receptor and phosphoinositide-3-kinase/Akt pathway.
AB  - Nitric oxide (NO) inhibits proliferation of subventricular zone (SVZ) neural
      precursor cells in adult mice in vivo under physiological conditions. The
      mechanisms underlying this NO effect have now been investigated using SVZ-derived
      neural stem cells, which generate neurospheres in vitro when stimulated by
      epidermal growth factor (EGF). In these cultures, NO donors decreased the number
      of newly formed neurospheres as well as their size, which indicates that NO was
      acting on the neurosphere-forming neural stem cells and the daughter neural
      progenitors. The effect of NO was cytostatic, not proapoptotic, and did not
      involve cGMP synthesis. Neurosphere cells expressed the neuronal and endothelial
      isoforms of NO synthase (NOS) and produced NO in culture. Inhibition of NOS
      activity by N(omega)-nitro-L-arginine methylester (L-NAME) promoted neurosphere
      formation and growth, thus revealing an autocrine/paracrine action of NO on the
      neural precursor cells. Both exogenous and endogenous NO impaired the EGF-induced
      activation of the EGF receptor (EGFR) tyrosine kinase and prevented the EGF
      induced Akt phosphorylation in neurosphere cells. Inhibition of the
      phosphoinositide-3-kinase (PI3-K)/Akt pathway by LY294002 significantly reduced
      the number of newly formed neurospheres, which indicates that this is an
      essential pathway for neural stem cell self-renewal. Chronic administration of l
      NAME to adult mice enhanced phospho-Akt staining in the SVZ and reduced nuclear
      p27(Kip1) in the SVZ and olfactory bulb. The inhibition of EGFR and PI3-K pathway
      by NO explains, at least in part, its antimitotic effect on neurosphere cells and
      may be a mechanism involved in the physiological role of NO as a negative
      regulator of SVZ neurogenesis in adult mice.

PMID- 16960137
TI  - Rat bone marrow progenitor cells transduced in situ by rSV40 vectors
      differentiate into multiple central nervous system cell lineages.
AB  - Using bone marrow-directed gene transfer, we tested whether bone marrow-derived
      cells may function as progenitors of central nervous system (CNS) cells in adult
      animals. SV40-derived gene delivery vectors were injected directly into femoral
      bone marrow, and we examined transgene expression in blood and brain for 0-16
      months thereafter by immunostaining for FLAG epitope marker. An average of 5% of
      peripheral blood cells and 25% of femoral marrow cells were FLAG(+) throughout
      the study. CNS FLAG-expressing cells were mainly detected in the dentate gyrus
      (DG) and periventricular subependymal zone (PSZ). Although absent before 1 month
      and rare at 4 months, DG and PSZ FLAG(+) cells were abundant 16 months after bone
      marrow injection. Approximately 5% of DG cells expressed FLAG, including neurons
      (48.6%) and microglia (49.7%), and occasional astrocytes (1.6%), as determined by
      double immunostaining for FLAG and lineage markers. These data suggest that one
      or more populations of cells resident within adult bone marrow can migrate to the
      brain and differentiate into CNS-specific cells.

PMID- 16960139
TI  - Rare diseases, orphan drugs, and orphaned patients.

PMID- 16960140
TI  - The calcineurin-NFAT pathway and bone: intriguing new findings.
AB  - New findings reveal that the calcineurin-NFAT signaling pathway helps to promote
      osteoblast differentiation. Three recent papers reveal somewhat different
      mechanisms by which this could occur. In one study, transduction of calcineurin
      Aalpha increased expression of osteoblast differentiation markers, including Runx
      2. In another study, NFATc1 cooperatively enhanced Osterix activation of the
      collagen 1a1 promoter, but did not enhance Runx-2 activity; evidence was provided
      for the formation of a novel NFATc1-Osterix complex. In a third study, expression
      of nuclear NFATc1 enhanced Wnt signaling. The observation that the Wnt pathway
      promotes bone formation is intriguing, because NFATc1 also is critical for
      osteoclastogenesis. The current findings could be relevant for the osteoporosis
      seen in patients given the calcineurin inhibitor cyclosporine to prevent
      transplant rejection, although the results need to be reconciled with aspects of
      the clinical picture.

PMID- 16960141
TI  - How specific are "target-specific" drugs? Celecoxib as a case in point.
AB  - With the push to develop the next blockbuster drugs, continued surveillance of
      current bestsellers may not be given the full attention due. Upon wide-spread
      use, unexpected adverse effects begin to emerge. Although touted as highly
      specific, many of the newly developed drugs are likely to have secondary
      molecular targets-a potential cause of adverse effects. A molecular pharmacology
      approach that screens for multiple drug targets may shed light on the mechanisms
      that underlie both desired and adverse side-effects.

PMID- 16960142
TI  - COX-2 in inflammation and resolution.
AB  - Aspirin and the other NSAIDs have popularized the notion of inhibiting
      prostaglandins as a common anti-inflammatory strategy based on the erroneous
      premise that all eicosanoids are, within the context of inflammation, generally
      detrimental. However, our fascination with aspirin and the emergence of COX-2 has
      shown a more affable side to lipid mediators based on our increasing interest in
      the endogenous control of acute inflammation and in factors that mediate its
      resolution. Epilipoxins, for instance, are produced from aspirin's acetylation of
      COX-2 and together with Resolvins and COX-2-derived prostaglandins of the D(2)
      and J(2) series represent an increasingly important family of immunoregulatory
      lipid mediators with strong implications for disease control and drug discovery.

PMID- 16960143
TI  - BCL-xL regulates synaptic plasticity.
AB  - Mitochondria are the predominant organelle within many presynaptic terminals.
      During times of high synaptic activity, they affect intracellular calcium
      homeostasis and provide the energy needed for synaptic vesicle recycling and for
      the continued operation of membrane ion pumps. Recent discoveries have altered
      our ideas about the role of mitochondria in the synapse. Mitochondrial
      localization, morphology, and docking at synaptic sites may indeed alter the
      kinetics of transmitter release and calcium homeostasis in the presynaptic
      terminal. In addition, the mitochondrial ion channel BCL-xL, known as a protector
      against programmed cell death, regulates mitochondrial membrane conductance and
      bioenergetics in the synapse and can thereby alter synaptic transmitter release
      and the recycling of pools of synaptic vesicles. BCL-xL, therefore, not only
      affects the life and death of the cell soma, but its actions in the synapse may
      underlie the regulation of basic synaptic processes that subtend learning, memory
      and synaptic development.

PMID- 16960144
TI  - The pharmocogenomics of warfarin: closing in on personalized medicine.
AB  - Warfarin, a coumarin anticoagulant, is used worldwide for the treatment and
      prevention of thromboembolic disease. Warfarin therapy, however, can be difficult
      to manage because of the drug's narrow therapeutic index and the wide
      interindividual variability in patient response. It is now clear that genetic
      polymorphisms in genes influencing metabolism (CYP2C9) and pharmacodynamic
      response (VKORC1) are strongly associated with warfarin responsiveness. Optimal
      warfarin dosing in turn drives other positive anticoagulation-related outcomes.
      Therefore, a strong basic science argument is emerging for prospective genotyping
      of warfarin patients. Effective clinical translation would establish warfarin
      pharmacogenomics as a heuristic model for personalized medicine.

PMID- 16960145
TI  - Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for
      refractory cutaneous T-cell lymphoma (CTCL).
AB  - The activity and safety of the histone deacetylase inhibitor vorinostat
      (suberoylanilide hydroxamic acid, SAHA) were evaluated in patients with
      refractory cutaneous T-cell lymphoma (CTCL). Group 1 received vorinostat 400 mg
      daily, group 2 received vorinostat 300 mg twice daily for 3 days with 4 days
      rest, and group 3 received vorinostat 300 mg twice daily for 14 days with 7 days
      rest followed by 200 mg twice daily. Treatment continued until disease
      progression or intolerable toxicity. The primary objective was to determine the
      complete and partial response (PR) rate. Time to response (TTR), time to
      progressive disease (TTP), response duration (DOR), pruritus relief, and safety
      were determined. Thirty-three patients who had received a median of 5 prior
      therapies were enrolled. Eight patients achieved a PR, including 7 with advanced
      disease and 4 with Sezary syndrome. The median TTR, DOR, and TTP for responders
      were 11.9, 15.1, and 30.2 weeks, respectively. Fourteen of 31 evaluable patients
      had pruritus relief. The most common drug-related AEs were fatigue,
      thrombocytopenia, diarrhea, and nausea. The most common grade 3 or 4 drug-related
      AEs were thrombocytopenia and dehydration. Vorinostat demonstrated activity in
      heavily pretreated patients with CTCL. The 400 mg daily regimen had the most
      favorable safety profile and is being further evaluated.

PMID- 16960146
TI  - Association of a novel regulatory polymorphism (-938C>A) in the BCL2 gene
      promoter with disease progression and survival in chronic lymphocytic leukemia.
AB  - Bcl-2 plays a key role in the regulation of apoptosis. We investigated the role
      of a novel regulatory single-nucleotide polymorphism (-938C>A) in the inhibitory
      P2 BCL2 promoter in B-cell chronic lymphocytic leukemia (B-CLL). The -938C allele
      displayed significantly increased BCL2 promoter activity and binding of nuclear
      proteins compared with the A allele. Concomitantly, Bcl-2 protein expression in B
      cells from CLL patients carrying the -938 AA genotype was significantly increased
      compared with CC genotypes. Genotype distribution between 123 CLL patients (42
      AA, 55 AC, 26 CC) and 120 genotyped healthy controls (36 AA, 63 AC, 21 CC) was
      not significantly different, suggesting that genotypes of this polymorphism do
      not increase the susceptibility for B-CLL. However, median time from first
      diagnosis to initiation of chemotherapy and median overall survival were
      significantly shorter in patients with -938AA genotype (38 and 199 months,
      respectively) compared with AC/CC genotypes (120 and 321 months, respectively; P
      = .008 and P = .003, respectively). Multivariable Cox regression identified the
      BCL2-938AA genotype as an independent prognostic factor for the time to first
      treatment (hazard ratio [HR] 1.9; P = .034) together with disease stage at
      diagnosis (HR 2.5; P = .004) and ZAP-70 status (HR 3.0; P = .001). The BCL2-938AA
      genotype is associated with increased Bcl-2 expression and a novel unfavorable
      genetic marker in patients with B-CLL.

PMID- 16960147
TI  - Increased surveillance of cells in mitosis by human NK cells suggests a novel
      strategy for limiting tumor growth and viral replication.
AB  - The threat from cancer cells is inherently linked to cell-cycle progression, and
      viral genomes commonly replicate, for example, within episomes or proviruses,
      during mitosis. We report here that human natural killer (NK) cells bound cells
      in mitosis and attacked pathogenic cells in mitosis more effectively than the
      same cells in other stages of the cell cycle. Thus, cells in mitosis warrant and
      undergo heightened surveillance, a novel strategy for immunologic assessment of
      danger. Recognition of cells in mitosis involved ligation of activating NK-cell
      receptors and binding to target-cell hyaluronan, a component of the pericellular
      matrix known to be increased during mitosis. Direct interaction between
      activating NK-cell receptors and hyaluronan is possible, but other mechanisms
      consistent with our data are also discussed.

PMID- 16960148
TI  - Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a
      phase 2 trial.
AB  - In immunoglobulin light chain (AL) amyloidosis, amyloid fibril deposits derived
      from immunoglobulin light chains produced by a clonal plasma cell dyscrasia
      accumulate in tissues and damage vital organs. Treatment regimens used in
      multiple myeloma can be effective in AL amyloidosis; however, patients with this
      disease often tolerate these regimens poorly because of multisystem organ
      dysfunction. Thalidomide and lenalidomide have both been shown to be effective in
      myeloma. In this report, we describe results of a phase 2 trial of the use of
      lenalidomide, as a single agent and in combination with dexamethasone, for the
      treatment of AL amyloidosis. Thirty-four patients with AL amyloidosis, most with
      prior therapies, were enrolled in the trial. The initial dose of lenalidomide
      used (25 mg/d) was poorly tolerated; however, a reduced dose of 15 mg/d was
      generally well tolerated. Of 24 evaluable patients, 7 (29%) achieved a
      hematologic complete response and 9 (38%) achieved a partial hematologic
      response, for an overall hematologic response rate of 67%. Hematologic responses
      were also associated with clinical responses. Fatigue and myelosuppression were
      the most common treatment-related adverse events (35%), while thromboembolic
      complications (9%) were the most serious. Findings from this trial indicate that
      lenalidomide can be effective in treating AL amyloidosis.

PMID- 16960149
TI  - Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas.
AB  - Integrative genomic and gene-expression analyses have identified amplified
      oncogenes in B-cell non-Hodgkin lymphoma (B-NHL), but the capability of such
      technologies to localize tumor suppressor genes within homozygous deletions
      remains unexplored. Array-based comparative genomic hybridization (CGH) and gene
      expression microarray analysis of 48 cell lines derived from patients with
      different B-NHLs delineated 20 homozygous deletions at 7 chromosome areas, all of
      which contained tumor suppressor gene targets. Further investigation revealed
      that only a fraction of primary biopsies presented inactivation of these genes by
      point mutation or intragenic deletion, but instead some of them were frequently
      silenced by epigenetic mechanisms. Notably, the pattern of genetic and epigenetic
      inactivation differed among B-NHL subtypes. Thus, the P53-inducible PIG7/LITAF
      was silenced by homozygous deletion in primary mediastinal B-cell lymphoma and by
      promoter hypermethylation in germinal center lymphoma, the proapoptotic BIM gene
      presented homozygous deletion in mantle cell lymphoma and promoter
      hypermethylation in Burkitt lymphoma, the proapoptotic BH3-only NOXA was mutated
      and preferentially silenced in diffuse large B-cell lymphoma, and INK4c/P18 was
      silenced by biallelic mutation in mantle-cell lymphoma. Our microarray strategy
      has identified novel candidate tumor suppressor genes inactivated by genetic and
      epigenetic mechanisms that substantially vary among the B-NHL subtypes.

PMID- 16960151
TI  - Durable responses to imatinib in patients with PDGFRB fusion gene-positive and
      BCR-ABL-negative chronic myeloproliferative disorders.
AB  - Fusion genes derived from the platelet-derived growth factor receptor beta
      (PDGFRB) or alpha (PDGFRA) play an important role in the pathogenesis of BCR-ABL
      negative chronic myeloproliferative disorders (CMPDs). These fusion genes encode
      constitutively activated receptor tyrosine kinases that can be inhibited by
      imatinib. Twelve patients with BCR-ABL-negative CMPDs and reciprocal
      translocations involving PDGFRB received imatinib for a median of 47 months
      (range, 0.1-60 months). Eleven had prompt responses with normalization of
      peripheral-blood cell counts and disappearance of eosinophilia; 10 had complete
      resolution of cytogenetic abnormalities and decrease or disappearance of fusion
      transcripts as measured by reverse transcriptase-polymerase chain reaction (RT
      PCR). Updates were sought from 8 further patients previously described in the
      literature; prompt responses were described in 7 and persist in 6. Our data show
      that durable hematologic and cytogenetic responses are achieved with imatinib in
      patients with PDGFRB fusion-positive, BCR-ABL-negative CMPDs.

PMID- 16960150
TI  - Clinical relevance of mutations and gene-expression changes in adult acute
      myeloid leukemia with normal cytogenetics: are we ready for a prognostically
      prioritized molecular classification?
AB  - Recent molecular analyses of leukemic blasts from pretreatment marrow or blood of
      patients with acute myeloid leukemia (AML) and a normal karyotype, the largest
      cytogenetic subset (ie, 40%-49%) of AML, have revealed a striking heterogeneity
      with regard to the presence of acquired gene mutations and changes in gene
      expression. Multiple submicroscopic genetic alterations with prognostic
      significance have been discovered, including internal tandem duplication of the
      FLT3 gene, mutations in the NPM1 gene, partial tandem duplication of the MLL
      gene, high expression of the BAALC gene, and mutations in the CEBPA gene.
      Application of gene-expression profiling has also identified a gene-expression
      signature that appears to separate cytogenetically normal AML patients into
      prognostic subgroups, although gene-expression signature-based classifiers
      predicting outcome for individual patients with greater accuracy are needed.
      These and similar future findings are likely to have a major impact on the
      clinical management of cytogenetically normal AML not only in prognostication but
      also in selection of appropriate treatment, since many of the identified genetic
      alterations already constitute or will potentially become targets for specific
      therapeutic intervention. In this report, we review prognostic genetic findings
      in karyotypically normal AML and discuss their clinical implications.

PMID- 16960152
TI  - Human Langerhans-cell activation triggered in vitro by conditionally expressed
      MKK6 is counterregulated by the downstream effector RelB.
AB  - Environmentally exposed epithelial Langerhans cells (LCs) encounter diverse
      innate stress signals, which lead to the activation of complex intracellular
      signaling cascades. Among these, p38 MAPK is consistently phosphorylated. For
      which aspects of LC activation triggering of p38 signaling is sufficient remains
      to be elucidated. We show that conditional induction of a dominant active form of
      MAPK kinase 6 (d.a.MKK6), a direct upstream kinase of p38, in LCs efficiently
      induces the up-regulation of costimulatory molecules and enhances their T-cell
      stimulatory capacity. These immediate effects showed no or only a minor
      requirement for classical NF-kappaB signaling. Concomitant with LC activation,
      d.a.MKK6 induced the alternative NF-kappaB member RelB, whose nuclear
      localization marks mature DCs. Specific inhibition of nuclear RelB during
      d.a.MKK6-induced LC activation further enhanced their maturation state. This
      observation was validated using the p38 activator anisomycin, thus suggesting a
      novel LC intrinsic control mechanism regulated by RelB.

PMID- 16960153
TI  - Reversal of cardiac complications by deferiprone and deferoxamine combination
      therapy in a patient affected by a severe type of juvenile hemochromatosis (JH).
AB  - Juvenile hemochromatosis (JH) is a rare autosomal recessive disorder of iron
      metabolism, genetically heterogeneous. In JH, symptomatic organ involvement
      occurs as early as the second decade of life. Heart failure and/or arrhythmias
      are the most frequent causes of death. Phlebotomy is the safest, most effective,
      and most economic therapeutic approach in hemochromatosis patients but is not
      indicated during the treatment of severe congestive heart failure with unstable
      hemodynamic status. The treatment of iron overload in these prohibitive clinical
      situations has to be carried out using iron chelators. We report a case of heart
      failure in the setting of unrecognized juvenile hemochromatosis successfully
      treated by the simultaneous administration of deferoxamine and deferiprone. To
      our knowledge, this is the first patient affected by JH treated with combined
      chelation regimen.

PMID- 16960154
TI  - Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and
      proliferation signals in response to BAFF and APRIL.
AB  - Hodgkin lymphoma (HL) originates from the clonal expansion of malignant Hodgkin
      and Reed-Sternberg (HRS) cells. These B-cell-derived elements constitute less
      than 10% of the tumoral mass. The remaining tissue is comprised of an
      inflammatory infiltrate that includes myeloid cells. Myeloid cells activate B
      cells by producing BAFF and APRIL, which engage TACI, BCMA, and BAFF-R receptors
      on the B cells. Here, we studied the role of BAFF and APRIL in HL. Inflammatory
      and HRS cells from HL tumors expressed BAFF and APRIL. Unlike their putative
      germinal center B-cell precursors, HRS cells lacked BAFF-R, but expressed TACI
      and BCMA, a phenotype similar to that of plasmacytoid B cells. BAFF and APRIL
      enhanced HRS cell survival and proliferation by delivering nonredundant signals
      via TACI and BCMA receptors through both autocrine and paracrine pathways. These
      signals caused NF-kappaB activation; Bcl-2, Bcl-xL, and c-Myc up-regulation; and
      Bax down-regulation, and were amplified by APRIL-binding proteoglycans on HRS
      cells. Interruption of BAFF and APRIL signaling by TACI-Ig decoy receptor, which
      binds to and neutralizes BAFF and APRIL, or by small-interfering RNAs targeting
      BAFF, APRIL, TACI, and BCMA inhibited HRS cell accumulation in vitro and might
      attenuate HL expansion in vivo.

PMID- 16960155
TI  - Homocysteine lowering by B vitamins and the secondary prevention of deep vein
      thrombosis and pulmonary embolism: A randomized, placebo-controlled, double-blind
      trial.
AB  - The Vitamins and Thrombosis (VITRO) study investigated the effect of homocysteine
      lowering by daily supplementation of B vitamins on the risk reduction of deep
      vein thrombosis (DVT) and pulmonary embolism (PE). Patients between 20 to 80
      years old with a first objectively confirmed proximal DVT or PE in the absence of
      major risk factors and a homocysteine concentration above the 75th percentile of
      a reference group were asked to participate (hyperhomocysteinemic group). A
      similar study was conducted in a random sample of patients with a homocysteine
      below the 75th percentile of the reference group (normohomocysteinemic group).
      After informed consent was obtained, patients were randomized to daily
      multivitamin supplementation (5 mg folic acid, 50 mg pyridoxine, and 0.4 mg
      cyanocobalamin) or placebo and were followed for 2.5 years. End points were
      objectively diagnosed recurrent DVT or PE. A total of 701 patients were enrolled
      (360 in the hyperhomocysteinemic and 341 in the normohomocysteinemic group). The
      number of recurrent events of venous thrombosis was 43 of 353 in the vitamin
      group (54/1000 py) and 50 of 348 in the placebo group (64/1000 py). The hazard
      ratio associated with vitamin treatment was 0.84 (95% CI, 0.56-1.26): 1.14 (95%
      CI, 0.65-1.98) in the hyperhomocysteinemic group and 0.58 (95% CI, 0.31-1.07) in
      the normohomocysteinemic group. The results of our study do not show that
      homocysteine lowering by B vitamin supplementation prevents recurrent venous
      thrombosis.

PMID- 16960157
TI  - Nutrition, chronic disease, and the problem of proof.

PMID- 16960156
TI  - Phospholipase C, calcium, and calmodulin are critical for alpha4beta1 integrin
      affinity up-regulation and monocyte arrest triggered by chemoattractants.
AB  - During inflammation, monocytes roll on activated endothelium and arrest after
      stimulation by proteoglycan-bound chemokines and other chemoattractants. We
      investigated signaling pathways downstream of G protein-coupled receptors (GPCRs)
      that are relevant to alpha4beta1 integrin affinity up-regulation using formyl
      peptide receptor-transfected U937 cells stimulated with fMLP or stromal-derived
      factor-1alpha and human peripheral blood monocytes stimulated with multiple
      chemokines or chemoattractants. The up-regulation of soluble LDV peptide or
      vascular cell adhesion molecule-1 (VCAM-1) binding by these stimuli was
      critically dependent on activation of phospholipase C (PLC), inositol 1,4,5
      triphosphate receptors, increased intracellular calcium, influx of extracellular
      calcium, and calmodulin, suggesting that this signaling pathway is required for
      alpha4 integrins to assume a high-affinity conformation. In fact, a rise in
      intracellular calcium following treatment with thapsigargin or ionomycin was
      sufficient to induce binding of ligand. Blockade of p44/42 and p38 mitogen
      activated protein (MAP) kinases, phosphoinositide 3-kinase, or protein kinase C
      (PKC) signaling did not inhibit chemoattractant-induced LDV or VCAM-1 binding.
      However, activation of PKC by phorbol ester up-regulated alpha4beta1 affinity
      with kinetics distinct from those of GPCR signaling. A critical role for PLC and
      calmodulin was also established for leukocyte arrest and adhesion strengthening.

PMID- 16960158
TI  - Genetics of obesity in Hispanic children.

PMID- 16960159
TI  - The underappreciated role of muscle in health and disease.
AB  - Muscle plays a central role in whole-body protein metabolism by serving as the
      principal reservoir for amino acids to maintain protein synthesis in vital
      tissues and organs in the absence of amino acid absorption from the gut and by
      providing hepatic gluconeogenic precursors. Furthermore, altered muscle
      metabolism plays a key role in the genesis, and therefore the prevention, of many
      common pathologic conditions and chronic diseases. Nonetheless, the maintenance
      of adequate muscle mass, strength, and metabolic function has rarely, if ever,
      been targeted as a relevant endpoint of recommendations for dietary intake. It is
      therefore imperative that factors directly related to muscle mass, strength, and
      metabolic function be included in future studies designed to demonstrate optimal
      lifestyle behaviors throughout the life span, including physical activity and
      diet.

PMID- 16960160
TI  - Body fat distribution and risk of type 2 diabetes in the general population: are
      there differences between men and women? The MONICA/KORA Augsburg cohort study.
AB  - BACKGROUND: It remains controversial whether body mass index (BMI), waist
      circumference (WC), or waist-hip ratio (WHR) is a better risk predictor of type 2
      diabetes. OBJECTIVE: The objective was to examine the sex-specific relevance of
      WC, WHR, and BMI to the development of type 2 diabetes. DESIGN: The prospective
      population-based cohort study was based on 3055 men and 2957 women aged 35-74 y
      who participated in the second (1989-1990) or third (1994-1995) MONICA
      (Monitoring Trends and Determinants on Cardiovascular Diseases) Augsburg survey.
      The subjects were free of diabetes at baseline. Hazard ratios (HRs) were
      estimated from Cox proportional hazards models. RESULTS: During a mean follow-up
      of 9.2 y, 243 cases of incident type 2 diabetes occurred in men and 158 occurred
      in women. Multivariable-adjusted HRs across quartiles of BMI were 1.0, 1.37,
      2.08, and 4.15 in men and 1.0, 3.77, 4.95, and 10.58 in women; those of WC were
      1.0, 1.15, 1.57, and 3.40 in men and 1.0, 3.21, 3.98, and 10.70 in women; those
      of WHR were 1.0, 1.14, 1.80, and 2.84 in men and 1.0, 0.82, 2.06, and 3.51 in
      women. In joint analyses, the highest risk was observed in men and women with a
      high BMI in combination with a high WC and a high WHR. CONCLUSIONS: Both overall
      and abdominal adiposity were strongly related to the development of type 2
      diabetes. Because there was an additive effect of overall and abdominal obesity
      on risk prediction, WC should be measured in addition to BMI to assess the risk
      of type 2 diabetes in both sexes.

PMID- 16960161
TI  - Long-term follow-up of cardiovascular disease risk factors in children after an
      obesity intervention.
AB  - BACKGROUND: Data concerning the long-term improvement of cardiovascular disease
      (CVD) risk factors after an obesity intervention in children are limited.
      OBJECTIVE: We studied changes in weight status and CVD risk factors in children
      in an intervention program and evaluated whether these changes were sustained 1 y
      after the end of the intervention. DESIGN: We analyzed changes in the SD score
      (SDS) of body mass index [BMI; in kg/m2 (SDS-BMI)], blood pressure (BP), lipids,
      and homeostasis model assessment index of insulin resistance (HOMA-IR) over the
      course of 2 y in 240 obese (BMI > 97th percentile) children aged 6-14 y (x age:
      10.4 y; x BMI: 26.9). Of these 240 children, 203 participated in a 1-y
      intervention program of physical exercise, nutrition education, and behavior
      therapy. We compared these children with 37 obese children who underwent no
      intervention and with 12 normal-weight children of the same age and sex. RESULTS:
      Obese children had significantly (P < 0.05) higher BP, HOMA-IR, and insulin,
      triacylglycerol, and LDL-cholesterol concentrations and lower HDL-cholesterol
      concentrations than did normal-weight children. Twenty-nine children dropped out
      of the intervention. Only in the 126 children who reduced their SDS-BMI did BP
      (8% and 12% decreases in systolic and diastolic BP, respectively), lipids (12%
      and 5% decreases in triacylglycerol and LDL cholesterol, respectively; 7%
      increase in HDL cholesterol), insulin (13% decrease), and HOMA-IR (17% decrease)
      improve significantly (P < 0.05). Reduction in SDS-BMI and all benefits regarding
      CVD risk factors were sustained 1 y after the end of the intervention in the
      children whose SDS-BMI decreased. CONCLUSIONS: Long-term multidisciplinary
      intervention led to a reduction in SDS-BMI in most of the obese children 1 y
      after the end of the intervention. Reduction in SDS-BMI was accompanied by an
      improvement in CVD risk factors.

PMID- 16960162
TI  - Novel soybean oils with different fatty acid profiles alter cardiovascular
      disease risk factors in moderately hyperlipidemic subjects.
AB  - BACKGROUND: A variety of soybean oils were developed with improved oxidative
      stability and functional characteristics for use as alternatives to partially
      hydrogenated fat. OBJECTIVE: The objective was to assess the effect of
      selectively bred and genetically modified soybean oils with altered fatty acid
      profiles, relative to common soybean and partially hydrogenated soybean oils, on
      cardiovascular disease risk factors. DESIGN: Thirty subjects (16 women and 14
      men) aged >50 y with LDL-cholesterol concentrations >130 mg/dL at screening
      consumed 5 experimental diets in random order for 35 d each. Diets contained the
      same foods and provided 30% of energy as fat, of which two-thirds was either
      soybean oil (SO), low-saturated fatty acid soybean oil (LoSFA-SO), high-oleic
      acid soybean oil (HiOleic-SO), low-alpha-linolenic acid soybean oil (LoALA-SO),
      or partially hydrogenated soybean oil (Hydrog-SO). RESULTS: Plasma phospholipid
      patterns reflected the predominant fat in the diet. LDL-cholesterol
      concentrations were 3.66 +/- 0.67(b), 3.53 +/- 0.77(b), 3.70 +/- 0.66(b), 3.71 +/
      0.64(a,b), and 3.92 +/- 0.70(a) mol/L; HDL-cholesterol concentrations were 1.32
      +/- 0.32(a,b), 1.32 +/- 0.35(b), 1.36 +/- 0.33(a), 1.32 +/- 0.33(b), and 1.32 +/-
      0.32(a,b) mol/L for the SO, LoSFA-SO, HiOleic-SO, LoALA-SO, and Hydrog-SO diets,
      respectively (values with different superscript letters are significantly
      different, P < 0.05). No significant effects were observed on VLDL-cholesterol,
      triacylglycerol, lipoprotein(a), and C-reactive protein concentrations or on
      ratios of LDL cholesterol to apolipoprotein B (apo B) and HDL cholesterol to apo
      A-I. Total cholesterol:HDL cholesterol was lower after subjects consumed the
      unhydrogenated soybean oils than after they consumed the Hydrog-SO diet.
      CONCLUSIONS: All varieties of soybean oils resulted in more favorable lipoprotein
      profiles than did the partially hydrogenated form. These soybean oils may provide
      a viable option for reformulation of products to reduce the content of trans
      fatty acids.

PMID- 16960163
TI  - Inflammatory proteins are related to total and abdominal adiposity in a healthy
      adolescent population: the AVENA Study.
AB  - BACKGROUND: In adults, obesity is characterized by a state of chronic low-grade
      inflammation accompanied by moderately high concentrations of acute phase
      inflammatory proteins. Recent results regarding C-reactive protein (CRP) point to
      a similar status in adolescents; however, studies of associations of the serum
      inflammatory proteins CRP, ceruloplasmin, and complement factors C3 and C4 with
      body fat distribution remain scarce. OBJECTIVE: We aimed to establish the
      possible relations of serum inflammatory proteins with body fat estimates and
      body fat distribution in an apparently healthy adolescent population. DESIGN:
      This report included 472 adolescents (248 males and 224 females) aged 13-18.5 y
      who were recruited from the Spanish cross-sectional multicenter AVENA Study for
      whom anthropometric and immunologic data were complete. The concentrations of the
      serum proteins and the in vitro production of cytokines (interleukin 6 and tumor
      necrosis factor alpha) by isolated and stimulated white blood cells were
      measured. Relations with anthropometric measurements were explored by using
      simple and partial correlations. RESULTS: CRP, C3, and C4 were correlated with
      central obesity (as measured by waist circumference) and total body fat in both
      sexes (P < 0.01) and with ceruloplasmin in females only. After further adjustment
      for BMI, C3 remained independently associated with central obesity (P < 0.05).
      Production of the cytokines by white blood cells did not seem to be affected by
      an excess of body fat. CONCLUSIONS: Total body fat seems to be associated with a
      chronic low-grade systemic inflammation in apparently healthy adolescents.
      Central obesity is independently associated with C3 concentrations, which makes
      this marker especially interesting for further studies of obesity-related
      diseases.

PMID- 16960164
TI  - Effect of varying the ratio of n-6 to n-3 fatty acids by increasing the dietary
      intake of alpha-linolenic acid, eicosapentaenoic and docosahexaenoic acid, or
      both on fibrinogen and clotting factors VII and XII in persons aged 45-70 y: the
      OPTILIP study.
AB  - BACKGROUND: Elevated fibrinogen, activated factor XII (FXIIa), and factor VII
      coagulant activity (FVIIc) are associated with higher risk of fatal ischemic
      heart disease. This study tested the hypothesis that lowering the dietary ratio
      of n-6 to n-3 polyunsaturated fatty acids (n-6:n-3) would modify these risk
      factors in older men and women. OBJECTIVE: The objective of the study was to
      measure fasting hemostatic risk factors and postprandial changes in activated
      FVII (FVIIa) concentrations after a 6-mo alteration in dietary n-6:n-3. DESIGN:
      In a randomized, parallel design in 258 subjects aged 45-70 y, we compared 4
      diets providing 6% of energy as polyunsaturated fatty acids at an n-6:n-3 between
      5:1 and 3:1 with a control diet that had an n-6:n-3 of 10:1. The diets were
      enriched in alpha-linolenic acid, eicosapentaenoic (EPA) and docosahexaenoic
      (DHA) acid, or both. RESULTS: Fasting and 3-h plasma triacylglycerol
      concentrations were 11.1% and 7.2% lower with the diet that had an n-6:n-3 of
      approximately 3:1 and that was enriched with EPA and DHA than with the other
      diets. Fasting fibrinogen, FXIIa, FVIIc, FVIIa, and FVII antigen and postprandial
      FVIIa were not influenced by the diets. Avoiding foods high in fat the day before
      measurement decreased FVIIc and FVIIa by 8% and 19.2%, respectively. A test meal
      containing 50 g fat resulted in a mean 47% (95% CI: 42%, 52%) increase in FVIIa 6
      h later, but the response did not differ by n-6:n-3. CONCLUSION: Decreasing the n
      6:n-3 to approximately 3:1 by increasing the intake of EPA and DHA lowers fasting
      and postprandial plasma triacylglycerol concentrations in older persons but does
      not influence hemostatic risk factors.

PMID- 16960165
TI  - Energy balance and the accuracy of reported energy intake in preadolescent
      children with cystic fibrosis.
AB  - BACKGROUND: Suboptimal growth and nutritional status are common among children
      with cystic fibrosis (CF) and pancreatic insufficiency (PI). A better
      understanding of energy balance is required to improve prevention and treatment
      of malnutrition. OBJECTIVE: Our objective was to characterize energy balance and
      the reporting accuracy of dietary intake in children with CF by evaluating the
      relations between energy intake (EI), energy expenditure (EE), fecal energy loss,
      nutritional status, and growth. DESIGN: The subjects were participants of a 24-mo
      prospective study of children 6-10 y of age with CF and PI. EE, EI, fecal energy
      loss, and anthropometric measures were obtained at baseline and at 24 mo.
      RESULTS: The children (n = 69) had suboptimal growth at baseline (x +/- SD:
      weight-for-age z score, -0.53 +/- 1.19; adjusted height-for-age z score, -0.67 +/
      1.06; body mass index z score, -0.29 +/- 1.12), and these variables remained
      suboptimal at 24 mo. The median ratios of EI to EE at baseline and 24 mo were
      1.15 and 1.18, respectively, which decreased to 1.09 and 1.10, respectively, when
      adjusted for fecal energy loss (EI(-FL):EE). At baseline, 7% of subjects were
      underreporters, 64% were accurate reporters, and 23% were overreporters of energy
      intake; the percentages were similar at 24 mo. CONCLUSIONS: Although EI(-FL):EE
      ratios were higher than expected at both baseline and 24 mo, this cohort showed
      only age-appropriate weight gain. Self-reported dietary intake data at the
      individual level should be interpreted with caution, and weight gain velocity may
      serve as an objective measure of long-term energy balance.

PMID- 16960166
TI  - Effect of acute dietary standardization on the urinary, plasma, and salivary
      metabolomic profiles of healthy humans.
AB  - BACKGROUND: Metabolomics in human nutrition research is faced with the challenge
      that changes in metabolic profiles resulting from diet may be difficult to
      differentiate from normal physiologic variation. OBJECTIVE: We assessed the
      extent of intra- and interindividual variation in normal human metabolic profiles
      and investigated the effect of standardizing diet on reducing variation. DESIGN:
      Urine, plasma, and saliva were collected from 30 healthy volunteers (23 females,
      7 males) on 4 separate mornings. For visits 1 and 2, free food choice was
      permitted on the day before biofluid collection. Food choice on the day before
      visit 3 was intended to mimic that for visit 2, and all foods were standardized
      on the day before visit 4. Samples were analyzed by using 1H nuclear magnetic
      resonance spectroscopy followed by multivariate data analysis. RESULTS: Intra-
      and interindividual variations were considerable for each biofluid. Visual
      inspection of the principal components analysis scores plots indicated a
      reduction in interindividual variation in urine, but not in plasma or saliva,
      after the standard diet. Partial least-squares discriminant analysis indicated
      time-dependent changes in urinary and salivary samples, mainly resulting from
      creatinine in urine and acetate in saliva. The predictive power of each model to
      classify the samples as either night or morning was 85% for urine and 75% for
      saliva. CONCLUSIONS: Urine represented a sensitive metabolic profile that
      reflected acute dietary intake, whereas plasma and saliva did not. Future
      metabolomics studies should consider recent dietary intake and time of sample
      collection as a means of reducing normal physiologic variation.

PMID- 16960167
TI  - Effects of n-3 fatty acids in subjects with type 2 diabetes: reduction of insulin
      sensitivity and time-dependent alteration from carbohydrate to fat oxidation.
AB  - BACKGROUND: Effects of fish oil supplements on metabolic variables are
      insufficiently clarified in type 2 diabetes. OBJECTIVE: We aimed to investigate
      short-term (1 wk) and longer-term (9 wk) effects of n-3 fatty acids. DESIGN:
      Twenty-six subjects with type 2 diabetes without hypertriacylglycerolemia
      participated in a double-blind controlled study. Median intake in the
      intervention group was 17.6 mL fish oil/d (1.8 g 20:5n-3, 3.0 g 22:6n-3, and 5.9
      g total n-3 fatty acids). The control group received 17.8 mL corn oil/d (8.5 g
      18:2n-6). RESULTS: Plasma phospholipid 20:5n-3 and 22:6n-3 increased, whereas
      18:2n-6 decreased, in the fish oil group compared with the corn oil group after 1
      wk. The two n-3 fatty acids also increased in adipose tissue biopsy samples taken
      after 9 wk in the fish oil group. Glucose concentrations (home-monitored) were
      approximately 1 mmol/L higher in the fish oil group than in the corn oil group at
      the end of the intervention (P = 0.035). Glucose utilization measured by using an
      isoglycemic clamp was lowered in the fish oil group compared with that in the
      corn oil group at the end of the intervention (P = 0.049), whereas glucagon
      stimulated C-peptide tended to increase (P = 0.078). The fish oil group utilized
      less fat for oxidation after 1 wk, with a change to more fat and less
      carbohydrate oxidation after 9 wk (P = 0.040), than did the corn oil group.
      CONCLUSION: A high intake of fish oil moderately increases blood glucose and
      decreases insulin sensitivity in persons with type 2 diabetes without
      hypertriacylglycerolemia and alters carbohydrate and fat utilization in a time
      dependent manner.

PMID- 16960168
TI  - An extract of black, green, and mulberry teas causes malabsorption of
      carbohydrate but not of triacylglycerol in healthy volunteers.
AB  - BACKGROUND: In vitro studies suggest that extracts of black, green, and mulberry
      teas could interfere with carbohydrate and triacylglycerol absorption via their
      ability to inhibit alpha-amylase, alpha-glucosidase, sodium-glucose transporters,
      and pancreatic lipase. OBJECTIVE: We measured breath hydrogen and 13CO2 to
      investigate the ability of an extract of black, green, and mulberry tea leaves to
      induce malabsorption of carbohydrate and triacylglycerol in healthy volunteers.
      DESIGN: In a crossover design, healthy adult volunteers randomly ingested test
      meals with a placebo beverage or a preparation containing an extract of black
      (0.1 g), green (0.1 g), and mulberry (1.0 g) teas. One test meal contained 50 g
      carbohydrate as white rice, 10 g butter, and 0.2 g [13C]triolein, and the
      beverages contained 10 g sucrose. The calorie content of the second test meal
      consisted entirely of lipid (30 g olive oil and 0.2 g [13C]triolein). Breath
      hydrogen and 13CO2 concentrations were assessed hourly for 8 h, and symptoms were
      rated on a linear scale. RESULTS: With the carbohydrate-containing meal, the tea
      extract resulted in a highly significant increase in breath-hydrogen
      concentrations, which indicated appreciable carbohydrate malabsorption. A
      comparison of hydrogen excretion after the carbohydrate-containing meal with that
      after the nonabsorbable disaccharide lactulose suggested that the tea extract
      induced malabsorption of 25% of the carbohydrate. The tea extract did not cause
      triacylglycerol malabsorption or any significant increase in symptoms.
      CONCLUSION: This study provides the basis for additional experiments to determine
      whether the tea extract has clinical utility for the treatment of obesity or
      diabetes.

PMID- 16960169
TI  - Higher fasting plasma concentrations of glucagon-like peptide 1 are associated
      with higher resting energy expenditure and fat oxidation rates in humans.
AB  - BACKGROUND: Glucagon-like peptide 1 (GLP-1) is a gut hormone that decreases
      appetite and promotes satiety. Its role in energy metabolism regulation is still
      poorly understood. OBJECTIVE: The aim of the study was to investigate the
      relation of fasting plasma GLP-1 concentrations to rates of energy expenditure
      (EE) and substrate oxidation-ie, respiratory quotient (RQ). DESIGN: Forty-six
      glucose-tolerant white subjects (22 men, 24 women) aged 18-49 y whose adiposity
      spanned a wide range [body mass index (in kg/m2): 18.5-50] were studied in an
      inpatient clinic. Main outcome measures included resting EE and RQ (ventilated
      hood technique), body composition (dual-energy X-ray absorptiometry), and fasting
      plasma concentrations of GLP-1, pancreatic polypeptide, glucose, and insulin.
      RESULTS: Fasting plasma GLP-1 concentrations were positively associated with
      resting EE (after adjustment for age, sex, and body composition) and negatively
      correlated with RQ (after adjustment for age, sex, and percentage body fat) and
      fasting plasma pancreatic polypeptide concentrations (both before and after
      adjustment for age, sex, percentage body fat, and fasting plasma glucose and
      insulin concentrations). Adjustment for fasting plasma pancreatic polypeptide
      concentrations, a marker of parasympathetic outflow to the gut, attenuated the
      strength of the association of fasting plasma GLP-1 concentrations with resting
      EE and RQ. CONCLUSIONS: Higher fasting plasma GLP-1 concentrations are associated
      with higher rates of EE and fat oxidation independent of age, sex, and body
      composition. The autonomic nervous system may have a role in this relation. This
      effect, along with the established role of GLP-1 in promoting satiety, may
      further foster its therapeutic potential in the treatment of obesity.

PMID- 16960170
TI  - Effects of tomato extract on platelet function: a double-blinded crossover study
      in healthy humans.
AB  - BACKGROUND: Aqueous extracts from tomatoes display a range of antiplatelet
      activities in vitro. We previously showed that the active components also alter
      ex vivo platelet function in persons with a high response to ADP agonist.
      OBJECTIVE: The objective was to evaluate the suitability of a tomato extract for
      use as a dietary supplement to prevent platelet activation. DESIGN: A randomized,
      double-blinded, placebo-controlled crossover study was conducted in 90 healthy
      human subjects selected for normal platelet function. Changes from baseline
      hemostatic function were measured 3 h after consumption of extract-enriched or
      control supplements. RESULTS: Significant reductions in ex vivo platelet
      aggregation induced by ADP and collagen were observed 3 h after supplementation
      with doses of tomato extract equivalent to 6 (6TE) and 2 (2TE) tomatoes [3
      micromol ADP/L: 6TE (high dose), -21.3%; 2TE (low dose), -12.7%; P < 0.001; 7.5
      micromol ADP/L: 6TE, -7.8%, 2TE, -7.6%; P < 0.001; 3 mg collagen/L: 6TE, -17.5%;
      2TE, -14.6%; P = 0.007]. No significant effects were observed for control
      supplements. A dose response to tomato extract was found at low levels of
      platelet stimulation. Inhibition of platelet function was greatest in a subgroup
      with the highest plasma homocysteine (P < 0.05) and C-reactive protein
      concentrations (P < 0.001). CONCLUSION: As a functional food or dietary
      supplement, tomato extract may have a role in primary prevention of
      cardiovascular disease by reducing platelet activation, which could contribute to
      a reduction in thrombotic events.

PMID- 16960171
TI  - Effects of antiplatelet components of tomato extract on platelet function in
      vitro and ex vivo: a time-course cannulation study in healthy humans.
AB  - BACKGROUND: Natural antithrombotic agents that influence platelet function are of
      potential interest for primary prevention of cardiovascular disease. Previous
      reports showed that tomato extracts inhibit platelet aggregation in vitro, but
      little is known of the active components, their mode of action, or their efficacy
      in vivo. OBJECTIVE: The objectives of the study were to examine the antiplatelet
      activity of specific tomato components by in vitro experimentation and to
      establish their ex vivo efficacy in healthy humans. DESIGN: The mechanisms of
      action of antiplatelet components isolated from tomato extracts were examined in
      vitro. A 7-h time-course study was carried out in cannulated human subjects (n =
      23) to determine the ex vivo efficacy of a supplement drink containing tomato
      extract and the onset and duration of antiplatelet effects. RESULTS: The
      inhibition of ADP-, collagen-, thrombin-, and arachidonate-mediated platelet
      aggregation by tomato extract components appears to be linked to the inhibition
      of glycoprotein IIb/IIIa and platelet secretory mechanisms. We found a
      significant inhibition of baseline platelet function, from 2.9 +/- 1.4% (optimal
      ADP concentrations; P = 0.03) to 20.0 +/- 4.9% (suboptimal ADP concentrations; P
      < 0.001), 3 h after supplementation with a dose of tomato extract equivalent to 6
      tomatoes. The observed effects persisted for >12 h. Coagulation variables were
      not affected. CONCLUSIONS: The ingestion of tomato components with in vitro
      antiplatelet activity significantly affects ex vivo platelet function. The
      reported cardioprotective effects of tomatoes are potentially linked to a
      modulation of platelet function.

PMID- 16960172
TI  - Vitamin A supplementation in children with poor vitamin A and iron status
      increases erythropoietin and hemoglobin concentrations without changing total
      body iron.
AB  - BACKGROUND: Vitamin A deficiency impairs iron metabolism; vitamin A
      supplementation of vitamin A-deficient populations may reduce anemia. The
      mechanism of these effects is unclear. In vitro and in animal models, vitamin A
      treatment increases the production of erythropoietin (EPO), a stimulant of
      erythropoiesis. OBJECTIVE: We measured the effect of vitamin A supplementation on
      hemoglobin, iron status, and circulating EPO concentrations in children with poor
      iron and vitamin A status. DESIGN: In a double-blind, randomized trial, Moroccan
      schoolchildren (n = 81) were given either vitamin A (200,000 IU) or placebo at
      baseline and at 5 mo. At baseline, 5 mo, and 10 mo, hemoglobin, indicators of
      iron and vitamin A status, and EPO were measured. RESULTS: At baseline, 54% of
      children were anemic; 77% had low vitamin A status. In the vitamin A group at 10
      mo, serum retinol improved significantly compared with the control group (P <
      0.02). Vitamin A treatment increased mean hemoglobin by 7 g/L (P < 0.02) and
      reduced the prevalence of anemia from 54% to 38% (P < 0.01). Vitamin A treatment
      increased mean corpuscular volume (P < 0.001) and decreased serum transferrin
      receptor (P < 0.001), indicating improved iron-deficient erythropoiesis. Vitamin
      A decreased serum ferritin (P < 0.02), suggesting mobilization of hepatic iron
      stores. Calculated from the ratio of transferrin receptor to serum ferritin,
      overall body iron stores remained unchanged. In the vitamin A group at 10 mo, we
      observed an increase in EPO (P < 0.05) and a decrease in the slope of the
      regression line of log10(EPO) on hemoglobin (P < 0.01). CONCLUSION: In children
      deficient in vitamin A and iron, vitamin A supplementation mobilizes iron from
      existing stores to support increased erythropoiesis, an effect likely mediated by
      increases in circulating EPO.

PMID- 16960173
TI  - Lignan and isoflavone excretion in relation to uterine fibroids: a case-control
      study of young to middle-aged women in the United States.
AB  - BACKGROUND: Uterine fibroids are hormonally responsive; estradiol and
      progesterone stimulate their growth, and gonadotrophin-releasing hormone agonists
      shrink them. Phytoestrogens, including isoflavones and lignans, can act as weak
      estrogens or antiestrogens. OBJECTIVE: The objective of this case-control study
      was to evaluate the relation between uterine fibroid risk and phytoestrogen
      exposure. DESIGN: Two overnight urine collections (48 h apart) from 170 uterine
      fibroid cases and 173 controls were analyzed for isoflavonoids (ie, daidzein,
      genistein, equol, and O-desmethylangolensin) and lignans (enterodiol and
      enterolactone). Logistic regression was used to determine associations between
      the mean excretion of the 2 collections and the risk of uterine fibroids.
      RESULTS: Unadjusted isoflavone excretion did not differ significantly between
      cases and controls (2.33 +/- 5.82 and 2.60 +/- 5.90 nmol/mg Cr, respectively; P =
      0.68), but cases excreted significantly less lignans than did controls (2.86 +/-
      3.45 and 4.57 +/- 6.67 nmol/mg Cr, respectively; P < 0.01). The trend for a
      reduced risk of uterine fibroids with increasing quartiles of lignan excretion
      was significant (odds ratio for highest versus lowest quartile = 0.31; 95% CI:
      0.17, 0.58; P for trend < 0.01). When adjusted for age, BMI, race, family history
      of uterine fibroids, and isoflavone excretion, this trend remained but was
      attenuated (P = 0.07). CONCLUSIONS: Our findings suggest a modest inverse
      association between lignan excretion and uterine fibroid risk. Whether this
      relation represents an effect of lignans per se or of other constituents of
      lignan-containing foods on the development of uterine fibroids remains to be
      determined. No association was found between isoflavone excretion and uterine
      fibroids; however, the intake of soy foods, the primary source of isoflavones,
      was low in this population.

PMID- 16960174
TI  - Zinc supplementation does not affect growth, morbidity, or motor development of
      US term breastfed infants at 4-10 mo of age.
AB  - BACKGROUND: It has been documented that growth patterns differ between breastfed
      and formula-fed infants. Some investigators have suggested that these differences
      may be related to differences in zinc nutriture. OBJECTIVE: The objective of this
      study was to examine the effect of zinc supplementation on growth, morbidity, and
      motor development in healthy, term, breastfed infants. DESIGN: We conducted a
      randomized double-blind intervention comparing zinc supplementation (5 mg/d as
      zinc sulfate) with placebo in breastfed infants aged 4-10 mo. Growth and indexes
      of body composition and gross motor development were measured monthly from 3 to
      10 mo. Morbidity data were collected weekly. RESULTS: Eighty-five infants were
      enrolled, and 70 completed the study. The baseline characteristics, attained
      weight or length at 10 mo, growth velocity, gross motor development, and
      morbidity did not differ significantly between groups, even after control for
      potentially confounding variables. CONCLUSIONS: The dietary zinc intake of these
      breastfed infants appeared to be adequate, given that zinc supplementation did
      not affect growth, development, or risk of infection (although sample size for
      detection of differences in development or infection was limited). Previously
      described differences in growth between breastfed and formula-fed infants in such
      populations do not appear to be due to differences in zinc nutriture.

PMID- 16960175
TI  - Optimal vitamin D status and serum parathyroid hormone concentrations in African
      American women.
AB  - BACKGROUND: Optimal vitamin D status for the prevention of osteoporosis has been
      inferred from examinations of the serum 25-hydroxyvitamin D [25(OH)D]
      concentration below which there is an increase in serum parathyroid hormone
      (PTH). OBJECTIVE: The objectives of the study were to ascertain whether a
      threshold for serum 25(OH)D exists below which serum PTH increases and whether
      persons with 25(OH)D above this threshold have lower rates of bone loss than do
      persons with 25(OH)D below the threshold. DESIGN: The relation of serum 25(OH)D
      to serum PTH was analyzed in 208 African American women studied longitudinally
      for 3 y. These healthy women in midlife were randomly assigned to receive placebo
      or 800 IU vitamin D3/d; after 2 y, the vitamin D3 supplementation was increased
      to 2000 IU/d. Both groups received calcium supplements to ensure an adequate
      calcium intake. A systematic literature review found a wide range of threshold
      values in part due to varied calcium intake. RESULTS: A Loess plot suggested a
      breakpoint between 40 and 50 nmol/L for serum 25(OH)D. A line-line model was
      fitted to the data, and it showed a spline knot at 44 nmol/L. A heuristic
      approach verified that PTH does not decline as rapidly when the serum
      concentration of 25(OH)D is >40 nmol/L as when it is <40 nmol/L. We found no
      significant difference in rates of bone loss between persons with 25(OH)D
      concentrations above and below 40 nmol/L. CONCLUSION: Although a threshold for
      25(OH)D can be identified, we suggest that it should not be used to recommend
      optimal vitamin D status.

PMID- 16960176
TI  - Synergy between mannose-binding lectin gene polymorphisms and supplementation
      with vitamin A influences susceptibility to HIV infection in infants born to HIV
      positive mothers.
AB  - BACKGROUND: Mannose-binding lectin (MBL-2) allele variants are associated with
      deficiencies in innate immunity and have been found to be correlated with HIV
      infection in adults and children. OBJECTIVE: We tested whether MBL-2 variants
      among infants born to HIV-positive mothers have an increased susceptibility to
      HIV. DESIGN: MBL-2 allele variants were measured among 225 infants born to HIV
      positive mothers enrolled in a trial in Durban, South Africa. Mothers of 108
      infants were randomly assigned to receive vitamin A and beta-carotene
      supplementation and 117 to receive placebo. Infants were followed with regular
      HIV tests to determine rates of mother-to-child HIV transmission. RESULTS: A high
      proportion of infants were either homozygous (10.7%) or heterozygous (32.4%) for
      MBL-2 variants. MBL-2 variants within the placebo arm were associated with an
      increased risk of HIV transmission (odds ratio: 3.09; 95% CI: 1.21, 7.86);
      however, MBL-2 variants within the supplementation arm were not associated with
      an increased risk of transmission (P = 0.04; test of interaction). Among infants
      with MBL-2 variants, supplementation was associated with a decreased risk of HIV
      transmission (odds ratio: 0.37; 95% CI: 0.15, 0.91). CONCLUSION: We observed what
      appears to be a gene-environment interaction between MBL-2 variants and an
      intervention with vitamin A plus beta-carotene that is relevant to mother-to
      child HIV transmission.

PMID- 16960177
TI  - Low serum concentrations of 25-hydroxyvitamin D in older persons and the risk of
      nursing home admission.
AB  - BACKGROUND: The prevalence of vitamin D deficiency in nursing home patients is
      high. OBJECTIVE: We aimed to ascertain whether lower serum 25-hydroxyvitamin D
      [25(OH)D] concentrations increase the risk of future nursing home admission and
      early death. DESIGN: We included 1260 independent, community-dwelling persons
      aged > or =65 y who were participating in the Longitudinal Aging Study Amsterdam
      (1995-1996). Study outcomes were time to nursing home admission during 6 y of
      follow-up and time to death until 1 April 2003. RESULTS: Vitamin D deficiency
      [25(OH)D < 25 nmol/L] and insufficiency [25(OH)D = 25-49.9 nmol/L] were present
      in 127 (10.1%) and 462 (36.7%) subjects, respectively. During follow-up, 138
      subjects (11.0%) were admitted to nursing homes, and 380 subjects (30.2%) died.
      The risk of nursing home admission for participants with 25(OH)D deficiency was
      53 cases per 1000 person-years higher than that for those with high 25(OH)D (> or
      =75 nmol/L) concentrations (58 compared with 5 cases). After adjustment for
      potential confounders, the hazard ratio (95% CI) of nursing home admission was
      3.48 (1.39, 8.75) for vitamin D-deficient, 2.77 (1.17, 6.55) for vitamin D
      insufficient, and 1.92 (0.79, 4.66) for vitamin D-borderline persons as compared
      with persons with high 25(OH)D (P for trend = 0.002). The results remained after
      additional adjustment for frailty indicators. Lower 25(OH)D was associated with
      higher mortality risk, but this association was not significant after adjustment
      for frailty indicators. CONCLUSION: Lower serum 25(OH)D concentrations in older
      persons are associated with a greater risk of future nursing home admission and
      may be associated with mortality.

PMID- 16960178
TI  - Co-ingestion of protein and leucine stimulates muscle protein synthesis rates to
      the same extent in young and elderly lean men.
AB  - BACKGROUND: The progressive loss of skeletal muscle mass with aging is attributed
      to a disruption in the regulation of skeletal muscle protein turnover. OBJECTIVE:
      We investigated the effects on whole-body protein balance and mixed-muscle
      protein synthesis rates of the ingestion of carbohydrate with or without protein
      and free leucine after simulated activities of daily living. DESIGN: Eight
      elderly (75 +/- 1 y) and 8 young (20 +/- 1 y) lean men were randomly assigned to
      2 crossover experiments in which they consumed either carbohydrate (CHO) or
      carbohydrate plus protein and free leucine (CHO+Pro+Leu) after performing 30 min
      of standardized activities of daily living. Primed, continuous infusions with L
      [ring-13C6]phenylalanine and L-[ring-2H2]tyrosine were applied, and blood and
      muscle samples were collected to assess whole-body protein turnover and the
      protein fractional synthetic rate in the vastus lateralis muscle over a 6-h
      period. RESULTS: Whole-body phenylalanine and tyrosine flux were significantly
      higher in the young than in the elderly men (P < 0.01). Protein balance was
      negative in the CHO experiment but positive in the CHO+Pro+Leu experiment in both
      groups. Mixed-muscle protein synthesis rates were significantly greater in the
      CHO+Pro+Leu than in the CHO experiment in both the young (0.082 +/- 0.005%/h and
      0.060 +/- 0.005%/h, respectively; P < 0.01) and the elderly (0.072 +/- 0.006%/h
      and 0.043 +/- 0.003%/h, respectively; P < 0.01) subjects, with no significant
      differences between groups. CONCLUSIONS: Co-ingestion of protein and leucine with
      carbohydrate after activities of daily living improves whole-body protein
      balance, and the increase in muscle protein synthesis rates is not significantly
      different between lean young and elderly men.

PMID- 16960179
TI  - Patterns, distribution, and determinants of under- and overnutrition: a
      population-based study of women in India.
AB  - BACKGROUND: Little systematic evidence exists for the relation between
      socioeconomic position and nutritional status in countries experiencing the
      simultaneous presence of under- and overnutrition. OBJECTIVE: We investigated the
      socioeconomic distribution of nutritional status in India and whether state-level
      macroeconomic factors modify the relation between socioeconomic position and
      nutritional status. DESIGN: Our analysis was based on a nationally representative
      sample of 77 220 women from India, with multiple categories of body mass index
      (BMI; in kg/m2) as the outcome, namely, <18.5 (underweight), 23-24.9 (pre
      overweight), 25-29.9 (overweight), or > or =30 (obese), with 18.5-22.9 as the
      reference category. RESULTS: In adjusted models, being underweight was inversely
      related to socioeconomic position, whereas socioeconomic position was positively
      related to being pre-overweight, overweight, and obese, and the socioeconomic
      gradient was most marked for obesity. State-level measures of affluence did not
      modify the positive association between socioeconomic position and categories of
      overweight. The risk of underweight was lower in affluent states, but this was
      seen mainly in women of high socioeconomic position. CONCLUSIONS: Undernutrition
      and overnutrition are epidemics of the impoverished and the affluent,
      respectively, in India, and this association is consistent at the individual and
      ecologic levels. Policies should focus on the complex patterns of social
      distribution of both under- and overnutrition in the Indian context.

PMID- 16960180
TI  - Association between dietary glycemic index, glycemic load, and body mass index in
      the Inter99 study: is underreporting a problem?
AB  - BACKGROUND: The few studies examining the potential associations between glycemic
      index (GI), glycemic load (GL), and body mass index (BMI) have provided no clear
      pictures. Underreporting of energy intake may be one explanation for this.
      OBJECTIVE: We examined the associations between GI, GL, and BMI by focusing on
      the confounding factor of total energy intake and the effect of exclusion of low
      energy reporters (LERs). DESIGN: This was a cross-sectional study of 6334
      subjects aged 30-60 y. Dietary intake was estimated from a food-frequency
      questionnaire. GI and GL were estimated by using white bread as the reference
      food. Underreporting of energy intake was assessed as reported energy intake
      divided by basal metabolic rate (EI/BMR); LERs were defined as those having an
      EI/BMR < 1.14. Univariate and multiple linear regression models were used to test
      for associations between GI, GL, and BMI. The confounders were sex, age, smoking,
      physical activity, alcohol intake, and energy intake. All analyses were conducted
      on 1) the entire population and 2) a subsample excluding LERs. RESULTS: In the
      univariate analyses of the entire population, GL was inversely associated with
      BMI. No association was observed for GI. After full adjustment (including energy
      intake), both GI and GL were positively associated with BMI. When LERs were
      excluded, GL was positively associated with BMI in all analyses, and GI was
      positively associated with BMI in the multiple analyses. CONCLUSIONS: We showed a
      positive association between GI, GL, and BMI. Energy adjustment and the exclusion
      of LERs significantly affected the results of the analysis; thus, we stress the
      importance of energy adjustment.

PMID- 16960181
TI  - Viva la Familia Study: genetic and environmental contributions to childhood
      obesity and its comorbidities in the Hispanic population.
AB  - BACKGROUND: Genetic and environmental contributions to childhood obesity are
      poorly delineated. OBJECTIVE: The Viva la Familia Study was designed to
      genetically map childhood obesity and its comorbidities in the Hispanic
      population. The objectives of this report were to describe the study design and
      to summarize genetic and environmental contributions to the phenotypic variation
      in obesity and risk factors for metabolic diseases in Hispanic children. DESIGN:
      The Viva la Familia cohort consisted of 1030 children from 319 families selected
      based on an overweight proband between the ages of 4 and 19 y. In-depth
      phenotyping to characterize the overweight children and their siblings included
      anthropometric and body-composition traits by dual-energy X-ray absorptiometry
      and assessments of diet by 24-h recalls, physical activity by accelerometry, and
      risk factors for metabolic diseases by standard biochemical methods. Univariate
      quantitative genetic analysis was used to partition phenotypic variance into
      additive genetic and environmental components by using the computer program
      SOLAR. RESULTS: Sex, age, and environmental covariates explained 1-91% of the
      phenotypic variance. Heritabilities of anthropometric indexes ranged from 0.24 to
      0.75. Heritability coefficients for the body-composition traits ranged from 0.18
      to 0.35. Diet and physical activity presented heritabilities of 0.32 to 0.69.
      Risk factors for metabolic diseases were heritable with coefficients ranging from
      0.25 to 0.73. Significant genetic correlations between obesity traits and risk
      factors for metabolic diseases substantiated pleiotropy between traits.
      CONCLUSION: The Viva la Familia Study provides evidence of a strong genetic
      contribution to the high prevalence of obesity and its comorbidities in Hispanic
      children.

PMID- 16960182
TI  - Predictors of nutrition counseling behaviors and attitudes in US medical
      students.
AB  - BACKGROUND: Nutrition counseling by physicians can improve patients' dietary
      behaviors and is affected by physicians' nutrition practices and attitudes, such
      as the perceived relevance of nutrition counseling. OBJECTIVE: The objective was
      to provide data on medical students' perceived relevance of nutrition counseling,
      reported frequency of nutrition counseling, and frequency of fruit and vegetable
      intakes. DESIGN: Students (n = 2316) at 16 US medical schools were surveyed and
      tracked at freshmen orientation, at the time of orientation to wards, and in
      their senior year. RESULTS: Freshmen students were more likely (72%) to find
      nutrition counseling highly relevant than were students at the time of ward
      orientation (61%) or during their senior year (46%; P for trend = 0.0003). Those
      intending to subspecialize had lower and declining perceptions of counseling
      relevance (P for trend = 0.0009), whereas the perceived relevance of counseling
      by primary care specialists remained high (P for trend = 0.5). Students were
      significantly more likely to find nutrition counseling highly relevant if they
      were female, consumed more fruit and vegetables, believed in primary prevention,
      had personal physicians who encouraged disease prevention, or intended to
      specialize in primary care. Only 19% of students believed that they had been
      extensively trained in nutrition counseling, and 17% of seniors reported that
      they frequently counseled their patients about nutrition. Students who consumed
      more fruit and vegetables, believed that they would be more credible if they ate
      a healthy diet, were not Asian or white, or intended to specialize in primary
      care counseled patients about nutrition more frequently. Medical students
      consumed an average of 3.0 fruit and vegetable servings/d, which declined over
      time. CONCLUSIONS: The perceived relevance of nutrition counseling by US medical
      students declined throughout medical school, and students infrequently counseled
      their patients about nutrition. Interventions may be warranted to improve the
      professional nutritional practices of medical students.

PMID- 16960183
TI  - Survival and body fat in hemodialysis patients: true association or effects of
      concomitant therapy?

PMID- 16960184
TI  - Effect of a high-fat meal on the postprandial ghrelin response.

PMID- 16960185
TI  - Is the consumption of oxidized fats contributing to HIV-AIDS progression in South
      Africa?

PMID- 16960186
TI  - Zinc, infectious diseases, and low birth weight.

PMID- 16960187
TI  - Non-steroidal anti-inflammatory drugs after hip replacement.

PMID- 16960188
TI  - Ageism in services for transient ischaemic attack and stroke.

PMID- 16960189
TI  - Predictive genetic testing for type 2 diabetes.

PMID- 16960190
TI  - Tackling alcohol misuse at the front line.

PMID- 16960191
TI  - The human tissue act.

PMID- 16960193
TI  - Children get "weak" services in most NHS trusts.

PMID- 16960194
TI  - Troops are needed in Darfur, says UN.

PMID- 16960195
TI  - Calcium channel blockers associated with less diabetes.

PMID- 16960196
TI  - Roche employee wins partial victory.

PMID- 16960197
TI  - Unexploded ordnance threatens Lebanese population, says UN.

PMID- 16960199
TI  - US judge dismisses 50m dollars damages in Vioxx lawsuit.

PMID- 16960200
TI  - Fewer boys born in New York after 9/11 attacks.

PMID- 16960202
TI  - More US citizens lack health insurance.

PMID- 16960203
TI  - Society issues guidance on IVF.

PMID- 16960204
TI  - Failure to tackle refugees' health needs increases risk of exclusion.

PMID- 16960205
TI  - Israeli cancer patients resume hunger strike.

PMID- 16960207
TI  - Keeping Paice with reforms.

PMID- 16960208
TI  - Acute appendicitis.

PMID- 16960209
TI  - Benign prostatic hyperplasia: treatment in primary care.

PMID- 16960210
TI  - Acute renal failure induced by contrast medium: steps towards prevention.

PMID- 16960212
TI  - Challenges for educationalists.

PMID- 16960213
TI  - Evidence based checklists for objective structured clinical examinations.

PMID- 16960214
TI  - Evidence based diagnosis: prior probability saves money, time, and possibly
      lives.

PMID- 16960215
TI  - Evidence based diagnosis: terminology is unsatisfactory.

PMID- 16960216
TI  - Evidence based diagnosis: multiple tests with multiple responses are important.

PMID- 16960217
TI  - Evidence based diagnosis: we may need to be open to new ideas.

PMID- 16960218
TI  - Strange things happen when we never qualify the frequency.

PMID- 16960219
TI  - Subarachnoid haemorrhage: lumbar puncture for every negative scan? Authors'
      reply.

PMID- 16960220
TI  - Evidence based diagnosis: what about the patients?

PMID- 16960221
TI  - Exempting mental health units from smoke-free laws: issue should no longer be
      ignored.

PMID- 16960222
TI  - Exempting mental health units from smoke-free laws: nicotine can have beneficial
      effects.

PMID- 16960223
TI  - Early intervention in acute renal failure: evidence of inadequate intravenous
      fluid treatment in UK hospitals.

PMID- 16960224
TI  - Early intervention in acute renal failure: assessing fluid status is important.

PMID- 16960225
TI  - Three Bs, please: more academic excellence, please.

PMID- 16960226
TI  - Three Bs, please: don't despise excellence.

PMID- 16960227
TI  - HIV cannot be tackled in isolation.

PMID- 16960228
TI  - Does activity engagement protect against cognitive decline in old age?
      Methodological and analytical considerations.
AB  - The literature about relationships between activity engagement and cognitive
      performance is abundant yet inconclusive. Some studies report that higher
      activity engagement leads to lower cognitive decline; others report no functional
      links, or that higher cognitive performance leads to less decline in activity
      engagement. We first discuss some methodological and analytical features that may
      contribute to the divergent findings. We then apply a longitudinal dynamic
      structural equation model to five repeated measurements of the Swiss
      Interdisciplinary Longitudinal Study on the Oldest Old. Performance on perceptual
      speed and verbal fluency tasks was analyzed in relation to six different activity
      composite scores. Results suggest that increased media and leisure activity
      engagement may lessen decline in perceptual speed, but not in verbal fluency or
      performance, whereas cognitive performance does not effect change in activity
      engagement.

PMID- 16960229
TI  - Filial piety and psychological well-being in well older Chinese.
AB  - Chinese older persons (N = 164) recruited from social centers responded to a
      survey instrument tapping the perceived filial behaviors of children (close vs
      not close), and the degree to which these behaviors matched personal expectations
      (filial discrepancy). Across all kinds of filial behaviors, providing attention
      when the parent was ill or distressed was perceived to be the least performed and
      was most discrepant with expectations. Whether the children were paying respect
      and whether they were providing care in times of illness or distress were most
      important in determining a sense of filial discrepancy in the parent. However,
      after functional limitations and financial strain were controlled for, only
      respect emerged as a consistent predictor of psychological well-being. These
      findings were similar whether the target was the closest child(ren) or less close
      children. There was no evidence that a child's overdoing his or her filial role
      was detrimental to the parents' well-being among the Chinese individuals in this
      study.

PMID- 16960230
TI  - Physical activity and functional limitations in older women: influence of self
      efficacy.
AB  - This study examined the role of self-efficacy and physical function performance
      in the relationship between physical activity and functional limitations. Older
      women (age, M = 68.2 years) completed measures of physical activity, self
      efficacy, physical function performance, and functional limitations at the
      baseline of an ongoing study. Analyses indicated that physical activity was
      associated with self-efficacy for exercise, efficacy for gait and balance, and
      physical function performance. Both measures of efficacy and physical functional
      performance were associated with functional limitations. Demographic and health
      status variables did not differentially influence these relationships. Although
      cross-sectional in nature, our findings suggest that physical activity, self
      efficacy, and functional performance may all play a role in reducing functional
      limitations. Of particular relevance is the fact that both physical activity and
      self-efficacy represent important, modifiable factors that can enhance function.

PMID- 16960231
TI  - Age differences in implicit interference.
AB  - We assessed age differences in interference effects in priming by using fragment
      completion. In Experiment 1, noninterfering filler words preceded critical
      targets at study, and priming was age invariant. In Experiment 2, the same target
      items had interfering competitors at the beginning of the list, such that both
      the target and the competitor were legitimate solutions to a fragment. Having two
      responses to a cue was disruptive for older adults, but not for younger adults.
      Younger and older adults differ in their susceptibility to interference in
      implicit tasks, and interference may play a role in influencing the magnitude of
      age differences in priming.

PMID- 16960232
TI  - Verbal learning and aging: combined effects of irrelevant speech, interstimulus
      interval, and education.
AB  - Older or lower educated individuals may be less able than younger or higher
      educated individuals to inhibit irrelevant speech when learning new visual
      information. In Experiment 1, we investigated the effects of age (four groups),
      educational attainment (low or high), and verbal noise (spoken words or silence)
      on word-learning performance in 230 individuals aged 24 to 76 years. Performance
      was negatively affected by age, lower education, and irrelevant speech, but there
      were no interactions between age group and noise condition. In Experiment 2, we
      increased the difficulty of the word-learning task by using both irrelevant
      speech and a short interstimulus interval (2 or 0.5 s). Age differences became
      more pronounced as the result of the simultaneous occurrence of irrelevant speech
      and a short interstimulus interval. This suggests that older individuals may need
      more time than younger individuals to learn new information in noisy
      environments.

PMID- 16960233
TI  - Coping, affect, and the metabolic syndrome in older men: how does coping get
      under the skin?
AB  - The metabolic syndrome is a complex construct with interrelated factors of
      obesity, blood pressure, lipids, and glucose. It is a risk factor for a number of
      chronic diseases in late life. This study tested a model in which the
      relationship between stress and the metabolic syndrome was mediated by appraisal,
      coping, and affect. Data were collected from 518 male participants in the
      Normative Aging Study (X(age) = 68.17 years). The model was partially confirmed.
      Relationships among stress, appraisal, coping, and affect were valenced along
      positive and negative pathways. However, affect was not directly related to the
      metabolic syndrome. The metabolic syndrome was related to positive coping as
      operationalized by self-regulatory strategies. The results of this study suggest
      that the influence of coping on physical health may occur through emotional
      regulation.

PMID- 16960234
TI  - The generalization of perceptual-motor intra-individual variability in young and
      old adults.
AB  - We examined the generalizability of intra-individual perceptual-motor variability
      in young and old adults. Participants completed four motor tasks that all
      required the maintenance of a steady state: finger tremor, and single-digit, two
      digit, and three-digit isometric force production. Older adults had a greater
      amount of variability and an increased time and frequency structure of
      variability, except in the tremor task. There was a moderate association between
      the magnitudes of variability across tasks in the oldest age group, but the
      structural measures of variability were more highly related across tasks and the
      strength of this relationship increased with age. These findings support the
      hypothesis that older adults are less able than younger adults to adapt the
      structure of their perceptual-motor variability to task demands.

PMID- 16960235
TI  - Correlates of caregiver-rated quality of life in assisted living: the Maryland
      Assisted Living study.
AB  - We used a cross-sectional study to examine the correlates of caregiver-rated
      quality of life (QOL) in 198 randomly selected residents from a stratified random
      sample of 22 assisted living facilities in central Maryland. We measured QOL by
      using the Alzheimer's Disease-Related Quality of Life Questionnaire. In general,
      despite cognitive impairment, residents in assisted living were rated as having a
      high QOL. In a multivariate regression, we found that nonmood neuropsychiatric
      symptoms were the strongest correlate of QOL, explaining 37% of the variance.
      Depressive symptoms, functional dependence, marital status, and cognition also
      contributed to the model, but only minimally. Because of the strong association
      of neuropsychiatric symptoms with QOL, special attention should be given to their
      recognition and amelioration.

PMID- 16960236
TI  - Snowbirds, sunbirds, and stayers: seasonal migration of elderly adults in
      Florida.
AB  - OBJECTIVE: Most migration statistics in the United States focus on changes in
      place of usual residence, thereby missing temporary moves such as business trips,
      vacations, and seasonal migration. In this article, we analyze the temporary in-
      and out-migration of elderly adults in Florida. Our primary objectives are to
      develop a methodology for estimating the number of temporary migrants and to
      analyze their demographic characteristics. METHODS: Using survey data, we
      estimated the number, timing, and duration of temporary moves and the origins,
      destinations, and characteristics of elderly temporary migrants. We compared the
      characteristics of temporary in-migrants, out-migrants, and non-migrants, and we
      used logistic regression analysis in order to evaluate differences in those
      characteristics. RESULT: We estimate that Florida had more than 800,000 elderly
      temporary in-migrants and more than 300,000 elderly temporary out-migrants at
      peak times in 2005. Income, education, employment, and health status were among
      the major determinants of temporary migration. DISCUSSION: The temporary
      migration of elderly adults has a major impact on the resident populations of
      both sending and receiving communities. This article presents a methodology for
      estimating temporary migration and provides insights into migratory patterns that
      cannot be achieved by focusing solely on changes in place of usual residence.

PMID- 16960237
TI  - After the fall of the Berlin Wall: perceptions and consequences of stability and
      change among middle-aged and older East and West Germans.
AB  - OBJECTIVES: This study empirically tested the self-systems theory of subjective
      change in light of the rapid change after the fall of the Berlin Wall. The theory
      predicts that individuals have a tendency to perceive stability and that
      perceived stability exerts a strong positive effect on subjective well-being. We
      would expect perceptions of decline and, to a lesser extent, perceptions of
      improvement to be related to lower levels of subjective well-being. METHODS: Data
      were from respondents aged 40-85 years who participated in the German Aging
      Survey. We used measures of well-being and temporal comparisons during the past
      10 years (1986-1996). RESULTS: West Germans reported more stability than East
      Germans, in particular in the public domain and in older age groups. Compared
      with perceptions of stability, perceptions of decline were related to less life
      satisfaction and more negative affect, and perceptions of growth to more negative
      affect. Temporal comparisons were unrelated to positive affect. DISCUSSION: Our
      findings both confirm and reject the self-systems theory of subjective change as
      it relates to the fall of the Berlin Wall. Studying temporal comparisons is
      important in understanding the effects of historical events and their timing
      within an individual life course.

PMID- 16960238
TI  - Parent care and the stress process: findings from panel data.
AB  - OBJECTIVE: The purpose of this study was to test with panel data an extended
      model of the stress process recognizing the separate effects of a parent's need
      for care and an adult child's caring activities. METHODS: Using data from the
      1996, 1998, and 2000 waves of the Health and Retirement Study, we estimated
      nonlinear mixed models of mental health outcomes. We assessed mental health for
      separate samples of 3,350 men and 3,659 women by using an 8-item scale of
      depressive symptoms. We also explored the sensitivity of results to alternative
      measures and model specifications. RESULT: We found that female, but not male,
      caregivers whose parents needed care exhibited adverse mental health
      consequences. However, we found that, generally, both male and female non
      caregivers whose parents needed care were more likely to report symptoms of
      depression than were non-caregivers without disabled parents. Additional findings
      suggest that the stress process is still more complex among married couples.
      DISCUSSION: This study distinguishes the outcomes of parental care needs from
      those attributable to caregiving activities. Adverse psychological outcomes
      appear to be dispersed throughout the family. To focus narrowly on active
      caregivers is to underestimate the social burdens of disability at older ages.

PMID- 16960239
TI  - Intergenerational transfers and living arrangements of older people in rural
      China: consequences for psychological well-being.
AB  - OBJECTIVE: The migration of working-age adults from rural to urban China has
      altered traditional patterns of living arrangements and intergenerational support
      among elderly persons who remain in rural regions. This investigation examined
      how household composition and support exchanges with adult children influenced
      the psychological well-being of older parents in rural China. METHODS: Data
      derived from a 2001 survey of 1,561 parents aged 60 and older living in rural
      Anhui Province, China. We used multiple regression in order to estimate the
      effects of multigenerational living arrangements and intergenerational transfers
      of financial, instrumental, and emotional support on depression and life
      satisfaction in older parents. RESULT: Older parents living in three-generation
      households or with grandchildren in skipped-generation households had better
      psychological well-being than those living in single-generation households.
      Receiving greater remittances from adult children increased well-being and
      explained why living with grandchildren was beneficial. Stronger emotional
      cohesion with children also improved well-being. DISCUSSION: These results
      suggest that traditional family arrangements are beneficial in rural Chinese
      society as they represent the fulfillment of a cultural ideal. We discuss
      implications in the context of the corporate Chinese family, characterized by
      mutual aid and interdependence across generations, and its adaptation to social
      change.

PMID- 16960240
TI  - Physical activity, public health, and aging: critical issues and research
      priorities.

PMID- 16960241
TI  - The impact of assistive device use on disability and depression among older
      adults with age-related vision impairments.
AB  - OBJECTIVE: One can conceptualize adaptive technology as a resource used by
      disabled older adults in order to maintain competence in everyday life. This
      study examined the independent relationships between optical and adaptive device
      utilization and change in functional disability and depression among older adults
      with age-related vision impairments. METHODS: We interviewed older adults (n =
      438) with a recent vision impairment applying for vision rehabilitation services
      both pre-service and at the 6-month follow-up. We conducted hierarchical
      regression analyses with functional disability and depressive symptoms as
      criteria. In order to identify their independent direct effects, we entered
      optical and adaptive device use into the final step, preceded by Time 1 criterion
      scores, demographics, baseline disability or depression (depending on criterion),
      and total rehabilitation service hours. RESULT: Optical, but not adaptive, device
      use was significantly associated with declines in functional disability and
      depressive symptoms over time. DISCUSSION: We propose that these differential
      effects result from the fact that optical devices optimize residual vision and
      thus allow for greater continuity in the way tasks are accomplished (i.e.,
      reading still performed visually), whereas use of adaptive aids (e.g., talking
      books) involves learning new methods in order to compensate for lost functions
      and thus is not as desirable either functionally or psychologically.

PMID- 16960242
TI  - The effects of the ACTIVE cognitive training trial on clinically relevant
      declines in health-related quality of life.
AB  - OBJECTIVES: The Advanced Cognitive Training for Independent and Vital Elderly
      (ACTIVE) study used three cognitive interventions (memory, reasoning, or speed of
      processing) in order to improve cognitive abilities. In this article, we evaluate
      ACTIVE's ability to avoid extensive decline in health-related quality of life
      (HRQoL). METHODS: ACTIVE enrolled 2,802 adults aged 65 or older and randomized
      them into one of three cognitive interventions or a no-contact control group.
      Researchers obtained data on 2,147 participants at the 24-month follow-up. We
      measured HRQoL by using the eight Short Form-36 scales, and we defined clinically
      relevant decline on each as a drop of 0.5 standard deviations from baseline. We
      defined extensive HRQoL decline as clinically relevant drops on four or more
      Short Form-36 scales, and we assessed this by using multiple logistic regression
      methods that adjusted for sociodemographic, cognitive, and health status
      covariates, and incorporated propensity score derived weights in order to adjust
      for potential attrition bias. RESULTS: We found that 25.0% of ACTIVE participants
      had extensive HRQoL decline. Participants in the speed-of-processing intervention
      arm were less likely to have extensive HRQoL decline (adjusted odds ratio =
      0.643; p =.004) compared with controls, and participants in the memory and
      reasoning arms were equivalent to controls (adjusted odds ratios = 1.149 and
      1.014, respectively; ps =.322 and.919, respectively). DISCUSSION: Although all
      three intervention arms improved cognitive ability, only the speed-of-processing
      arm protected against extensive clinically relevant decline in HRQoL.

PMID- 16960243
TI  - Medical therapy: where are we now?
AB  - PURPOSE: This article reviews the mechanisms of action, safety, and efficacy of
      the nonbiologic, or traditional, disease-modifying antirheumatic drugs (DMARDs),
      particularly methotrexate, sulfasalazine, leflunomide, and hydroxychloroquine. It
      also addresses various aspects of rheumatoid arthritis (RA) clinical trials that
      warrant careful interpretation, including response criteria, outcomes
      measurements, study designs, and results of combination therapy trials. SUMMARY:
      The considerable progress in the treatment of RA over the past 20 years is due in
      large part to a better understanding of how to use DMARDs optimally and the
      introduction of biologic agents. In addition to their ability to suppress
      inflammation, and thereby reduce symptoms of pain and stiffness, these drugs also
      have the potential to alter the course of RA by slowing disease progression and
      reducing joint damage. CONCLUSION: Studies have demonstrated that early treatment
      of RA and rapid suppression of inflammation are extremely important as they
      provide long-term benefits and improve the overall prognosis for patients with
      the disease.

PMID- 16960244
TI  - Use of biologics in rheumatoid arthritis: where are we going?
AB  - PURPOSE: The pharmacology, efficacy, safety, and costs of biologic agents that
      are approved by the Food and Drug Administration or are under review for the
      management of rheumatoid arthritis (RA) are discussed. Biologic therapies that
      are currently under investigation in early- and late-phase clinical trials are
      summarized at the end of this report. SUMMARY: The use of biologic agents for the
      treatment of RA has significantly improved the management of this disease.
      Experimental and clinical studies have shown that these agents ameliorate the
      signs and symptoms of RA, slow radiographic progression of disease, and improve
      physical function and quality of life. Data also support that early initiation of
      therapy with these agents improves long-term outcomes. However, biologic agents
      are associated with adverse effects that health care providers need to recognize
      and manage. CONCLUSION: Biologic agents have revolutionized the treatment of RA
      by reducing the signs and symptoms of RA, slowing radiographic progression of
      joint destruction, and improving physical function and quality of life in
      affected patients.

PMID- 16960246
TI  - Rheumatoid arthritis: a primer for pharmacists.
AB  - PURPOSE: The epidemiology of rheumatoid arthritis (RA), its pathophysiology and
      immune mechanisms, and its clinical manifestations are reviewed. The signs,
      symptoms, and radiographic and biochemical changes noted in mild, moderate, and
      severe disease are discussed and the systemic nature of RA and its adverse impact
      on survival are addressed. Traditional and newer scoring instruments to measure
      disease severity, progression, disability, and response to therapy are reviewed
      and introduced, respectively. The impact of RA on disability and quality of life
      (QOL) is also explored. SUMMARY: RA, a chronic inflammatory autoimmune disease
      that involves the synovial membrane and extraarticular sites, affects
      approximately 1-2% of the population, with women 2-3 times as likely to be
      affected as men. If RA is not treated aggressively, its clinical course is
      characterized by progressive physical disability and reduced QOL. CONCLUSION:
      Increased knowledge of the cellular and immune mechanisms involved in RA has
      identified new drug targets.

PMID- 16960247
TI  - Improving rheumatoid arthritis outcomes: how do we get there?

PMID- 16960249
TI  - Cardiology groups' antithrombotic guidelines challenge ACCP's.

PMID- 16960250
TI  - CMS releases inpatient payment rule for fiscal year 2007.

PMID- 16960251
TI  - Natural agents examined as sources for chemopreventive therapies.

PMID- 16960252
TI  - Pharmacy's changing demographics.

PMID- 16960253
TI  - Echinocandins in the management of invasive fungal infections, part 1.
AB  - PURPOSE: The chemistry, pharmacology, spectrum of activity, resistance,
      pharmacokinetics, pharmacodynamics, clinical efficacy, adverse effiects, drug
      interactions, dosage and administration, cost, and place in therapy of
      echinocandins are reviewed. SUMMARY: Three echinocandins are currently available:
      caspofungin, micafungin, and anidulafungin. The principal mechanism of action of
      the echinocandins is the noncompetitive inhibition of beta-(1,3)-dglucan
      synthase, an essential component of the cell wall of many fungi that is not
      present in mammalian cells. Echinocandins exhibit fungicidal activity against
      Candida species, including triazole-resistant isolates, and fungistatic activity
      against Aspergillus species. While fungistatic against mold, echinocandins may
      hold promise for the treatment of these pathogens when given in combination with
      amphotericin B or broad-spectrum triazoles, such as voriconazole. To date,
      resistance to echinocandins has been reported in only two patients. Echinocandins
      exhibit concentration- dependent activity against Candida species. In clinical
      trials, caspofungin has demonstrated efficacy in treating candidemia, esophageal
      candidiasis, and febrile neutropenia. Micafungin has demonstrated efficacy as
      antifungal prophylaxis in hematopoietic stem cell transplant recipients and in
      the treatment of esophageal candidiasis. Anidulafungin received approved labeling
      from the Food and Drug Administration in February 2006. Clinical efficacy data
      will be forthcoming. CONCLUSION: Echinocandins are fungicidal against yeast and
      fungistatic against mold. Their limited toxicity profile and minimal drug-drug
      interactions make them an attractive new option for the treatment of invasive
      fungal infections. Their cost may limit their use as initial therapy for patients
      with fungemia in medical centers or intensive care units with a high rate of
      triazoleresistant Candida infections.

PMID- 16960254
TI  - Unlabeled uses of nebulized medications.
AB  - PURPOSE: The uses, dosing recommendations, benefits, and disadvantages of
      unlabeled drugs administered by nebulization are reviewed. SUMMARY: Nebulization
      is gaining popularity as a treatment alternative, and many drugs are used
      unlabeled in a nebulized form, including the opioids, lidocaine, magnesium
      sulfate, amphotericin B, and colistin. The opioids are frequently used to treat
      dyspnea in end-stage diseases. Common dosages include 1-2 mg every two hours as
      needed for hydromorphone and 25-50 microg every two hours for fentanyl citrate.
      Lidocaine can be used to relieve bronchoconstriction and cough symptoms as well
      as acting as a local anesthetic. It is typically given in a dose between 20 and
      160 mg. Nebulized magnesium sulfate can be used in managing acute asthma and is
      given in dosages between 125 and 250 mg every 20 minutes, with no more than four
      consecutive doses. Nebulized amphotericin B can be used to prevent infections in
      immunocompromised patients. A typical amphotericin B regimen is 25 mg every 24
      hours. Nebulized colistin is being studied in the prevention and treatment of
      gram-negative infections and in patients awaiting lung transplants. Colistin is
      often given as 75 mg every 12 hours to combat infections. CONCLUSION: Unlabeled
      nebulization of opioids, lidocaine, magnesium, amphotericin B, and colistin is an
      alternative method of treatment for patients with pulmonary problems or
      infections or for those undergoing bronchoscopy. More research is needed to
      develop guidelines for their use since nebulization may provide benefits to many
      patients who otherwise cannot be treated or would be at risk of systemic adverse
      effects of the drugs.

PMID- 16960255
TI  - Statin use in American Indians and Alaska Natives with coronary artery disease.
AB  - PURPOSE: The use and adherence to statin therapy in American Indians and Alaska
      Natives with coronary artery disease (CAD) were studied. METHODS: A retrospective
      database analysis of the Phoenix Area of the Indian Health Service was conducted.
      For the cohort of patients with CAD, prescription data were obtained for all
      statins during calendar year 2003. Use was determined by the presence of at least
      one statin prescription, whereas adherence was assessed using the medication
      possession ratio (MPR), persistence, and median gap. RESULTS: The study cohort
      was composed of 2095 adults (55.6% men) with at least one medical encounter for
      CAD during calendar year 2002. The mean +/- S.D. age of the cohort was 62.7 +/-
      12.7 years. At least one prescription for any statin drug during 2003 was found
      for 865 (41.3%) patients. Those who received a statin were more likely to be
      male, be younger than 80 years, and have a greater number of medical visits. The
      mean MPR was 0.78 +/- 0.25, and nonadherence was found in approximately 40% of
      patients receiving statins. In the age category of 65-79 years, men were more
      adherent than women, and patients in this category were overall more adherent
      than younger patients. CONCLUSION: The use of statins in a cohort of American
      Indians and Alaska Natives at high risk for cardiovascular events was
      approximately 40% with a 60% adherence rate. Age, sex, and number of medical
      visits were associated with statin use, and age and sex were associated with
      adherence.

PMID- 16960256
TI  - Evaluation of patient and provider satisfaction with a pharmacist-managed lipid
      clinic in a Veterans Affairs medical center.
AB  - PURPOSE: Patient and provider satisfaction with a pharmacist-managed lipid clinic
      in a Veterans Affairs medical center were assessed. METHODS: All patients at
      Louis Stokes Cleveland Veterans Affairs Medical Center who were referred to a
      pharmacist-managed lipid clinic for drug therapy management were mailed a
      questionnaire addressing overall satisfaction with care provided by the lipid
      clinic. Chart reviews were performed for patients completing the questionnaire to
      ascertain lipid-lowering medications used, changes in serum cholesterol levels,
      and achievement of low-density-lipoprotein (LDL) cholesterol goal. Health care
      providers referring patients to the lipid clinic were sent an anonymous
      electronic questionnaire to assess provider satisfaction with the clinic.
      Responses to the questionnaire were rated on a Likert scale (strongly agree,
      somewhat agree, neutral, somewhat disagree, strongly disagree). A paired t test
      was used to assess the percent change in lipid values, and chi-square analysis
      was used to evaluate the achievement of each patient's LDL cholesterol goal.
      RESULTS: Surveys were sent to 224 patients and 104 providers. A total of 105
      patients (47%) and 49 providers (47%) completed the questionnaire. Most patients
      and providers expressed satisfaction with the clinic, with 91.4% of patients and
      87.8% of providers indicating that they were strongly or somewhat satisfied with
      the care provided by the pharmacist-managed clinic. Attainment rates of goal LDL
      cholesterol levels increased from 8.6% at baseline to 53.3% at discharge or the
      most recent measurement (p < 0.001). CONCLUSION: Most patients and providers were
      satisfied with the services provided by the pharmacist-managed lipid clinic. The
      clinic helped improve patients' LDL cholesterol, total cholesterol, and
      triglyceride levels.

PMID- 16960257
TI  - Monitoring of pharmacy staffing, workload, and productivity in community
      hospitals.
AB  - PURPOSE: The purpose of this survey was to identify and characterize pharmacy
      productivity monitoring systems used in community hospitals that were part of a
      national group purchasing organization (GPO). METHODS: A 50-item questionnaire
      was developed, pretested, and sent electronically to the directors of pharmacy at
      242 member hospitals of Consorta, Inc., a national GPO. The questionnaire was
      designed to elicit information on (1) hospital pharmacy demographics, (2) systems
      used to measure hospital pharmacy productivity, and (3) staffing levels and
      workload. Hospital demographic data were also obtained for respondent and
      nonrespondent hospitals from the American Hospital Association's AHA Guide.
      Descriptive statistics, Student's t tests, and chi-square tests were used to
      characterize the data and compare respondents with nonrespondents. RESULTS:
      Responses were received from 110 hospitals (45.5%). No clinically significant
      differences were found when respondent and nonrespondent hospitals were compared
      based on AHA Guide data. The productivity workload ratios monitored most often by
      respondent hospitals were full-time equivalents (FTEs) per adjusted patient day,
      FTEs per dose dispensed, and FTEs per dose billed. Respondents reported a mean +/
      S.D. of 21.90 +/- 18.83 actual FTEs and total doses dispensed, billed, or
      administered per year of 111,391.4 +/- 111,538.0. A major limitation of the
      productivity systems used in the hospitals was the inability of the systems to
      account for clinical services performed by the pharmacy staff. CONCLUSION: A
      survey of community hospitals indicated that although most engaged in
      productivity monitoring, systems for such measurement often failed to capture all
      relevant clinical workload data.

PMID- 16960258
TI  - Comparison of surface contamination with cyclophosphamide and fluorouracil using
      a closed-system drug transfer device versus standard preparation techniques.
AB  - PURPOSE: A comparison was conducted of the levels of surface contamination with
      two commonly used antineoplastic drugs, cyclophosphamide and fluorouracil, on
      countertops, floors, and hood surfaces in three oncology pharmacies following
      preparation with standard hazardous drug (HD) preparation techniques, or a closed
      system drug transfer device (CSTD) in conjunction with standard HD preparation
      techniques, or a CSTD in conjunction with standard HD preparation techniques but
      prepared on a countertop outside the biological safety cabinet (BSC). METHODS:
      Wipe samples of the various surfaces in each pharmacy were obtained biweekly for
      12 weeks (six samples) to establish a baseline. Following implementation of the
      CSTD, an additional six biweekly samples were collected. The CSTD was then
      removed, and a final six samples were collected again using standard preparation
      techniques. During the CSTD Phase, fluorouracil was prepared on the countertop
      outside the BSC. RESULTS: During the 36-week study, 342 samples were collected. A
      total of 8% positive fluorouracil wipe samples were found in the three
      pharmacies. The proportion of positive fluorouracil samples was significantly
      less in the CSTD Phase than in the control phases (p = 0.0002). There were 324
      (95%) positive cyclophosphamide wipe samples. The median surface contamination
      was significantly different across the three phases (p < 0.00001). This was
      consistent at all sites, for both the BSC work surfaces and countertops.
      Contamination on floors adjacent to the BSCs was not consistently reduced.
      CONCLUSION: The use of a CSTD in the BSC in conjunction with standard HD
      preparation techniques significantly reduced cyclophosphamide surface
      contamination as compared to standard techniques alone. Preparation of
      fluorouracil outside the BSC using the CSTD did not result in significant
      analytically detectable contamination on the countertops.

PMID- 16960260
TI  - Ensuring fairness in coverage decisions: applying the American Medical
      Association Ethical Force Program's consensus report to managed care pharmacy.

PMID- 16960261
TI  - Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell
      death.
AB  - Cell dysfunction and death induced by lipid accumulation in nonadipose tissues,
      or lipotoxicity, may contribute to the pathogenesis of obesity and type 2
      diabetes. However, the mechanisms leading to lipotoxic cell death are poorly
      understood. We recently reported that, in Chinese hamster ovary (CHO) cells and
      in H9c2 cardiomyoblasts, lipid overload induced by incubation with 500 muM
      palmitate leads to intracellular accumulation of reactive oxygen species, which
      subsequently induce endoplasmic reticulum (ER) stress and cell death. Here, we
      show that palmitate also impairs ER function through a more direct mechanism.
      Palmitate was rapidly incorporated into saturated phospholipid and triglyceride
      species in microsomal membranes of CHO cells. The resulting membrane remodeling
      was associated with dramatic dilatation of the ER and redistribution of protein
      folding chaperones to the cytosol within 5 h, indicating compromised ER membrane
      integrity. Increasing beta-oxidation, through the activation of AMP-activated
      protein kinase, decreased palmitate incorporation into microsomes, decreased the
      escape of chaperones to the cytosol, and decreased subsequent caspase activation
      and cell death. Thus, palmitate rapidly increases the saturated lipid content of
      the ER, leading to compromised ER morphology and integrity, suggesting that
      impairment of the structure and function of this organelle is involved in the
      cellular response to fatty acid overload.

PMID- 16960263
TI  - Factors affecting recovery and discharge following ambulatory surgery.
AB  - PURPOSE: Recovery and discharge following ambulatory surgery are important
      components of the ambulatory surgery experience. This review provides
      contemporary perspectives on the issues of discharge criteria, fast-tracking,
      patient escort requirements, and driving after ambulatory anesthesia. SOURCE: A
      search was performed in the Cochrane Central Register for Controlled Trials,
      MEDLINE(R), EMBASE(R), CINAHL, and PsycINFO, to review factors delaying discharge
      following ambulatory surgery. The following subject headings were used:
      "ambulatory surgery, discharge, recovery, car driving, escort, transport, fast
      tracking, patient discharge, recovery, transportation of patients, hospital
      discharge, recovery room, patient transport, hospital discharge, recovery room,
      anesthetic recovery, patient transport, ambulatory surgical procedures, patient
      discharge, recovery of function, automobile driving, patient escort service,
      recovery room". Using the same search engines, the following keywords were used:
      "fast tracking, recovery, and discharge". PRINCIPAL FINDINGS: The current
      literature supports that discharge scoring systems may be useful to guide
      discharge following ambulatory surgery. While fast-tracking has become common in
      some centres, further studies are required to justify more routine implementation
      of this practice in the management of patients undergoing ambulatory surgery.
      Patients at low risk for urinary retention can be discharged home without
      voiding. Patients should not drive until at least 24 hr postoperatively.
      CONCLUSIONS: Ensuring rapid postoperative recovery and safe discharge following
      ambulatory surgery are important components of the ambulatory surgical program. A
      clearly defined process should be established for each ambulatory surgical unit
      to ensure the safe and timely discharge of patients after anesthesia, in
      accordance with current best evidence.

PMID- 16960264
TI  - Induced hypotension with epidural/general anesthesia reduces transfusion in
      radical prostate surgery.
AB  - PURPOSE: Radical prostatectomy is associated with substantial blood loss
      frequently requiring allogeneic blood transfusion. We investigated the efficacy
      of deliberate hypotension using combined epidural/general anesthesia in reducing
      allogeneic transfusion requirements in patients undergoing radical prostatectomy.
      METHODS: In a prospective, randomized, single-blind trial, 102 patients
      undergoing radical prostatectomy were allocated to either an epidural group (n =
      51) or a control group (n = 51). In the epidural group, deliberate hypotension
      was achieved with a target mean arterial pressure of 55-60 mmHg. The trigger for
      allogeneic blood transfusion in both groups was a hematocrit value < 0.25.
      RESULTS: Operative blood loss in the epidural group was significantly less than
      that in the control group (955 +/- 517 mL vs 1477 +/- 823 mL respectively, P <
      0.001). The percentage of patients who reached the threshold trigger for
      allogenic transfusion was significantly less in the epidural group (8% vs 26%,
      respectively, P = 0.019) and the number of patients who were actually transfused
      during hospitalization was also significantly less (P = 0.028). There were no
      serious adverse events in either group during the study. CONCLUSION: Controlled
      hypotension using a combined epidural/ general anesthetic technique is associated
      with significantly less blood loss, and a reduction in the use of allogeneic
      blood in patients undergoing radical prostatectomy compared to general anesthesia
      alone.

PMID- 16960265
TI  - Case report: management of life-threatening oropharyngeal bleeding with
      recombinant factor VIIa.
AB  - PURPOSE: To report the use of recombinant factor VIIa (rFVIIa) for management of
      profuse oropharyngeal bleeding in a cirrhotic patient that nearly resulted in a
      'cannot intubate, cannot ventilate' scenario. CLINICAL FEATURES: A 42-yr-old
      woman with end-stage liver disease presented for orthotopic liver
      transplantation. She was dialysis dependent and had marked coagulopathy
      [international normalized ratio (INR) = 3.1], without evidence of active
      bleeding. Following uneventful induction of anesthesia, routine airway
      manipulation for tracheal intubation caused profuse upper airway bleeding making
      visualization of her airway by direct laryngoscopy impossible. Moreover, several
      further attempts at tracheal intubation along with the bleeding made manual
      ventilation progressively more difficult, nearly resulting in a 'cannot intubate,
      cannot ventilate' scenario. In an attempt to control the bleeding, rFVIIa 4.8 mg
      iv was administered. Within five minutes, her INR had decreased to 1.1, bleeding
      was markedly reduced, the vocal cords were successfully visualized using an
      anterior commissure laryngoscope, and intubation of the trachea was achieved with
      the use of a gum-elastic bougie. Postintubation examination of the airway showed
      several abrasions along the right oropharyngeal wall with minimal bleeding. The
      remainder of surgery and postoperative airway management were uneventful.
      CONCLUSIONS: This report demonstrates that in the relatively uncommon setting of
      upper airway hemorrhage in a patient with pre-existing coagulopathy, rFVIIa can
      be effective in gaining rapid control of bleeding to facilitate visualization of
      the vocal cords and securing of the airway.

PMID- 16960266
TI  - Preparation of the Drager Primus anesthetic machine for malignant hyperthermia
      susceptible patients.
AB  - PURPOSE: Preparation of anesthesia machines for patients who are susceptible to
      malignant hyperthermia includes flushing the machine with vapour-free fresh gas
      to washout residual anesthetic agents. To establish guidelines for the
      preparation of the Drager Primus machine, we compared the washout profiles for
      isoflurane and sevoflurane in the Drager Primus and Ohmeda Excel 210 anesthesia
      machines. TECHNICAL FEATURES: The machines were primed with 1.5% isoflurane or
      2.5% sevoflurane. Fresh gas flow (FGF) was set at 10 L.min(-1) during the early
      washout phase, and subsequently reduced to 3 L.min(-1) during the late washout
      phase. A Miran ambient air analyzer measured the anesthetic concentration every
      minute during washout until a concentration of 5 ppm was achieved in the
      inspiratory limb of the circle circuit. We found that at a FGF of 10 L.min(-1),
      maximum washout times for isoflurane and sevoflurane in the Primus, 70 and 74
      min, respectively, were approximately tenfold greater than for isoflurane in the
      Excel 210 (7.0 min). Increasing the FGF to 18 L.min(-1) decreased the washout
      time for isoflurane in the Primus, only moderately, to 52 min. We observed a
      threefold increase in anesthetic concentration in the Primus during the late
      washout phase. CONCLUSION: We conclude that the Primus must be flushed for at
      least 70 min to decrease the anesthetic concentration to 5 ppm when using a FGF
      of 10 L.min(-1). We recommend maintaining a FGF of 10 L.min(-1) for the duration
      of anesthesia in order to prevent the rebound increase in anesthetic
      concentration in the FGF.

PMID- 16960267
TI  - Ketamine and N-acetylaspartylglutamate peptidase inhibitor exert analgesia in
      bone cancer pain.
AB  - PURPOSE: Not all bone cancer pain can be effectively treated with current
      therapies. In the present study, the effects of ip administration of alpha-2
      agonists (dexmedetomidine and clonidine), N-methyl-D-aspartate (NMDA) antagonists
      (MK-801 and ketamine), an N-acetylaspartylglutamate peptidase inhibitor (ZJ-43),
      and morphine were examined in a mouse bone cancer pain model. METHODS: A bone
      cancer pain model was produced by injection of murine sarcoma cells into the
      medullary cavity of the distal femur. To estimate the level of bone cancer pain,
      the number of pain-related behaviours induced by repeated applications of a von
      Frey monofilament (0.166 g) to the site of tumour cells implantation was counted.
      Drugs were administered two weeks after the implantation. RESULTS: Morphine
      produced a significant analgesic effect (P < 0.001). The alpha-2 agonists
      produced analgesic effects (P < 0.001) with an efficacy similar to that of
      morphine, but only at doses that produced severe sedation. MK-801 had only
      limited analgesic effects, while ketamine produced an analgesic effect (P <
      0.001) with the same efficacy as morphine. ZJ-43 (100 mg.kg(-1)) had a
      significant analgesic effect (P < 0.05) and the effect of ZJ-43 was antagonized
      by the selective group II metabotropic glutamate receptor (mGluR) antagonist.
      CONCLUSION: These data suggest that alpha-2 agonists produce an analgesic effect
      only at a sedative dose and that ketamine, but not MK-801, is associated with an
      analgesic response without overt side effects. The effect of ZJ-43 is mediated by
      activating group II mGluRs.

PMID- 16960268
TI  - Epidural dexamethasone reduces postoperative pain and analgesic requirements.
AB  - PURPOSE: Epidural steroids may have potential advantages for providing
      postoperative analgesia. We therefore undertook a study to evaluate the efficacy
      of epidurally administered dexamethasone in reducing postoperative morphine
      requirements, as a measure of analgesia following laparoscopic cholecystectomy.
      METHODS: In a randomized, double-blind study, 94 patients undergoing laparoscopic
      cholecystectomy were randomly assigned to one of three groups. Group 1 (Control)
      patients received dexamethasone 5 mg iv with epidural injection of 0.25%
      bupivacaine 8 mL and normal saline 2 mL, Group 2 (D1) patients received normal
      saline 2 mL iv with epidural injection of 0.25% bupivacaine 8 mL and
      dexamethasone 5 mg in normal saline 2 mL, and Group 3 (D2) patients received
      normal saline 2 mL iv with epidural injection of dexamethasone 5 mg in normal
      saline 10 mL. After surgery, morphine 2-4 mg iv was administered as needed for
      analgesia. Postoperative morphine requirements, visual analogue scale (VAS) pain
      scores at rest and with effort, and time to first analgesic administration were
      recorded by a blinded observer. RESULTS: Total morphine consumption for the first
      24 hr following surgery was lower in both epidural dexamethasone groups (D1, D2)
      compared to the control group (P < 0.05). The percentage reduction in morphine
      consumption in Group D1 was 53.9% and in Group D2 was 52.9% in the first 24 hr.
      Postoperatively at 12 hr, 18 hr and 24 hr, the VAS scores at rest and during
      effort were also lower in the epidural dexamethasone groups (D1, D2) compared to
      the control group (P < 0.05). The percentage reductions in VAS scores with effort
      at 12 hr, 18 hr and 24 hr in Group D1 were 50%, 52.9% and 50% respectively, and
      in Group D2 percentage reductions in pain scores with effort were 54.8%, 58.8%
      and 55.5% at corresponding sampling intervals. CONCLUSION: Preoperative epidural
      administration of dexamethasone 5 mg, with or without bupivacaine, reduces
      postoperative pain and morphine consumption following laparoscopic
      cholecystectomy.

PMID- 16960269
TI  - The effects of volatile anesthetics on cardiac ischemic complications and
      mortality in CABG: a meta-analysis.
AB  - PURPOSE: Coronary artery bypass graft surgery (CABG) is associated with cardiac
      complications, including ischemia, acute myocardial infarction (AMI), and death.
      Volatile anesthetics have been shown to have a preconditioning-like effect. This
      systematic review assesses the effects of volatile anesthetics on cardiac
      ischemic complications and morbidity after CABG. METHODS: Data were obtained,
      without language restriction, from searches of MEDLINE, Science Citation Index,
      PubMed, and reference lists. We included only prospective randomized controlled
      trials evaluating volatile anesthetics during CABG. Two reviewers independently
      abstracted data on myocardial ischemia, acute myocardial infarction (AMI), and
      death. Treatment effects were calculated as odds ratio (OR) with 95% confidence
      intervals (CI) for binary data, and weighted mean difference (WMD) with 95% CI
      for continuous data. PRINCIPAL FINDINGS: Thirty-two studies (2,841 patients) were
      included. In comparison with iv anesthesia, volatile anesthetics were associated
      with reduced all-cause mortality (OR, 0.65; 95% CI, 0.36-1.18; P = 0.16).
      Enflurane was associated with increased AMI (OR, 1.34; 95% CI, 0.68-2.64; P =
      0.40), whereas sevoflurane and desflurane reduced cardiac troponin I (cTnI) at
      six hours, 12 hr, 24 hr [WMD, -1.45; 95% CI (-1.73, -1.16); P < 0.00001], and 48
      hr after operation. CONCLUSION: This meta-analysis demonstrates sevoflurane and
      desflurane reduce the postoperative rise in cTnI. Sevoflurane-mediated reduction
      in cardiac troponin was associated with improved long-term outcomes in one study.
      This meta-analysis was not able to show that these positive effects on troponin
      were translated into improved clinical outcomes. Well-designed large randomized
      control trials are needed to further elucidate the differential cardio-protective
      effects of volatile anesthetics.

PMID- 16960270
TI  - Continuous positive airway pressure does not improve lung function after cardiac
      surgery.
AB  - PURPOSE: Despite the well-documented impairment of pulmonary function after
      cardiopulmonary bypass, effective precautions and ideal management strategies for
      this problem are still under debate. This study aimed to evaluate the effects of
      continuous positive airway pressure (CPAP) applied during cardiopulmonary bypass
      on respiratory and hemodynamic variables. METHODS: In this randomized,
      prospective, controlled trial, 120 male patients, aged 45 to 70 yr undergoing
      first-time elective bypass surgery, were randomly assigned to receive either 10
      cm H2O of CPAP (Group I; n = 60) during cardiopulmonary bypass, or serve as
      control (Group II; n = 60), where the patient's lungs were vented to atmosphere
      during the bypass period. RESULTS: Alveolar-arterial oxygen partial pressure
      difference and shunt fraction were significantly higher in the control group
      compared with the CPAP group after cardiopulmonary bypass (T2) and after closure
      of sternum (T3), (P < 0.05). No differences between groups with respect to
      hemodynamic variables were observed at any time. Postoperative pulmonary function
      variables were lower in both groups compared to baseline values. CONCLUSIONS:
      Continuous positive airway pressure administered during cardiopulmonary bypass
      decreased shunt fraction and alveolar-arterial oxygen partial pressure difference
      during surgery, but had no sustained effect on either variable postoperatively.
      We conclude that, in patients with normal preoperative pulmonary function,
      application of 10 cm H2O CPAP does not improve lung function after cardiac
      surgery.

PMID- 16960271
TI  - Audit of factor VIIa for bleeding resistant to conventional therapy following
      complex cardiac surgery.
AB  - PURPOSE: There are an increasing number of anecdotal reports and trials of
      recombinant activated factor VII (rFVIIa) for bleeding during surgery. The
      reports of rFVIIa during cardiac surgery are limited. We report our experience
      using rFVIIa, in the operating room; to treat bleeding that prevented chest
      closure, despite appropriate conventional treatment, following complex cardiac
      surgery. METHODS: Retrospective chart review, at an Australian University
      hospital and associated private hospital, of cardiac surgery patients given
      rFVIIa (usual dose 90 microg.kg(-1)). We used rFVIIa for bleeding that prevented
      closure of the chest despite administration of blood products, protamine, and
      surgical attempts to secure hemostasis. RESULTS: Recombinant activated factor VII
      was administered on 55 occasions to 53 patients. Most patients had complex aortic
      or valve surgery. Median bypass time was 266 min. Before administering rFVIIa,
      patients received (median): packed red cells four units; platelets 15 units;
      fresh frozen plasma eight units; and cryoprecipitate ten units. After
      administering rFVIIa the median doses of donor blood products up to 12 hr after
      intensive care unit admission were: packed red cells one unit; platelets zero
      units; fresh frozen plasma zero units; and cryoprecipitate zero units. The
      decrease in doses of all blood products was significant (P < 0.001). We could not
      determine if rFVIIa played a role in significant mortality (19%) and morbidity
      (17%). CONCLUSION: Use of rFVIIa in cardiac surgery may be effective, but
      definitive clinical trials are needed to clarify its role in clinical practice
      and safety. We present an rFVIIa guideline developed during the audit period.

PMID- 16960272
TI  - Review article: organ perfusion/permeability-related effects of norepinephrine
      and vasopressin in sepsis.
AB  - PURPOSE: One invariable hallmark of severe sepsis is generalized tissue
      "malperfusion" and hyperpermeability secondary to microcirculatory/capillary
      leakage. This review focuses on direct and/or indirect influences of
      norepinephrine, as a standard of care, and vasopressin, as an alternative
      vasoactive drug, on organ and tissue perfusion/permeability in severe sepsis.
      SOURCE: English and French language articles and books published between 1966 and
      2005 were identified through a computerized Medline search using the terms
      "sepsis, permeability, norepinephrine and vasopressin". Relevant publications
      were retrieved and scanned for additional sources. PRINCIPAL FINDINGS: There are
      few randomized clinical trials comparing different vasopressors in sepsis; most
      available literature consists of clinical reports, animal experiments and
      occasional reviews. Based on the best current evidence from these sources, we
      describe the status of major organ perfusion/permeability in sepsis (i.e., the
      lung, the kidney, the heart, the intestine/gut) in the context of sepsis-induced
      organ dysfunction/failure. Potential and differential therapeutic effects of the
      vasopressors norepinephrine and arginine-vasopressin, in the setting of sepsis,
      are identified. CONCLUSIONS: In the treatment of sepsis, arginine-vasopressin
      exhibits organ-specific heterogeneity in vascular responsiveness, compared to
      norepinephrine. While norepinephrine is a current standard of care in sepsis,
      arginine-vasopressin shows promise for the treatment of septic shock.

PMID- 16960273
TI  - Best evidence in critical care medicine: treatment for hyperglycemia in the
      intensive care unit: a "bittersweet" message.

PMID- 16960274
TI  - Curriculum development in anesthesia: basic theoretical principles.
AB  - PURPOSE: Educational theories provide a guiding basis for coherent medical
      curriculum development and instruction in a similar way that evidence-based
      medicine provides a rational basis for medical treatment. The purpose of this
      review is to provide general organizational, theoretical and educational
      principles for developing or modifying an anesthesia curriculum. SOURCE: This
      paper draws from the general educational and cognitive psychology literature, the
      medical educational literature from the period 1996-2006, as well as our
      experience in renewing the anesthesia clerkship curriculum at McMaster
      University. PRINCIPAL FINDINGS: Successful curriculum development includes the
      consideration of stakeholder needs, organizational issues, funding and
      sustainability, curriculum design, implementation and evaluation. Curriculum
      design includes the development of curricular goals and objectives, determination
      of the content and its organization, instructional methods and strategies, and
      assessment of the learners. Curriculum evaluation is used to judge the
      curriculum's merit and worth. The findings and recommendations from these
      evaluations feed back into the curriculum development cycle for further
      curricular improvements or modifications. CONCLUSION: The current medical
      environment requires a responsive and efficacious curriculum that is able to keep
      up with its rapid pace of change. By providing a discussion of the educational
      and theoretical principles which underpin coherent curriculum development, this
      paper advocates a rational, theory-based approach to curriculum development.

PMID- 16960275
TI  - The ProSeal LMA does not cause laryngeal edema.

PMID- 16960276
TI  - Phosphate salt bowel preparation regimens alter perioperative acid-base and
      electrolyte balance.

PMID- 16960277
TI  - Spinal cord transmission of afferent neuronal activity despite surgical
      conduction anesthesia.

PMID- 16960278
TI  - Risks of dural puncture associated with thoracic epidurals.

PMID- 16960279
TI  - Biosorption of radioactive thorium by Sargassum filipendula.
AB  - In the present work, the biosorption of radioactive thorium was investigated
      using a dry biomass of Sargassum filipendula as the biosorbent material.
      Radioactive solutions containing between 2.0 and 500.0 microg thorium were tested
      by biosorption with S. filipendula, yielding uptake capacities from 20 to 100%,
      depending on the concentration of the solution. Kinetic studies indicated that
      equilibrium between the thorium solution and the solid fraction was achieved
      after three hours of contact and that a second-order model could express the
      equilibrium kinetics. In order to investigate the maximum biosorption capacity of
      the biomass an isotherm was done, based on the experimental data, which revealed
      the maximum uptake capacity to be 2.59 micromol thorium/g biomass. The
      experimental data fitted well to a Langmuir model, which provided a good
      correlation between the experimental and predicted thorium uptake values.

PMID- 16960280
TI  - A new method for microcapsule characterization: use of fluorogenic genipin to
      characterize polymeric microcapsule membranes.
AB  - Numerous microcapsule systems have been developed for a wide range of
      applications, including the sustained release of drugs, cell transplantation for
      therapy, cell immobilization, and other biotechnological applications. Despite
      the fact that microcapsule membrane is a dominant factor governing overall
      microcapsule performance, its characterization is challenging. We report a new
      method for characterizing microcapsule membranes, using the most common alginate
      poly-L-lysine-alginate (APA) microcapsule as an example. Our data demonstrate
      that genipin, a naturally derived reagent extracted from gardenia fruits,
      interacts with poly-L-lysine (PLL) and generates fluorescence. This fluorescence
      allows clear visualization and easy analysis of the PLL membrane in the APA
      microcapsules using confocal laser scanning microscopy. The results also show
      that PLL binding correlates to the reaction variables during PLL coating such as
      PLL concentration and coating time. In addition, five other different
      microcapsule formulations consisting of PLL and/or chitosan membranes were
      examined, and the results imply that this method can be extended to characterize
      a variety of microcapsule membranes. These findings suggest that genipin can
      serve as a fluorogenic marker for rapid characterization of microcapsule
      membranes, a superior method that would have important implications for
      microcapsule research and potential in many other applications.

PMID- 16960281
TI  - Lactic acid bacteria production from whey.
AB  - The main purpose of this work was to isolate and characterize lactic acid
      bacteria (LAB) strains to be used for biomass production using a whey-based
      medium supplemented with an ammonium salt and with very low levels of yeast
      extract (0.25 g/L). Five strains of LAB were isolated from naturally soured milk
      after enrichment in whey-based medium. One bacterial isolate, designated MNM2,
      exhibited a remarkable capability to utilize whey lactose and give a high biomass
      yield on lactose. This strain was identified as Lactobacillus casei by its 16S
      rDNA sequence. A kinetic study of cell growth, lactose consumption, and
      titratable acidity production of this bacterial strain was performed in a
      bioreactor. The biomass yield on lactose, the percentage of lactose consumption,
      and the maximum increase in cell mass obtained in the bioreactor were 0.165 g of
      biomass/g of lactose, 100%, and 2.0 g/L, respectively, which were 1.44, 1.11, and
      2.35 times higher than those found in flask cultures. The results suggest that it
      is possible to produce LAB biomass from a whey-based medium supplemented with
      minimal amounts of yeast extract.

PMID- 16960282
TI  - Optimization and modeling of laccase production by Trametes versicolor in a
      bioreactor using statistical experimental design.
AB  - Experimental design and response surface methodologies were applied to optimize
      laccase production by Trametes versicolor in a bioreactor. The effects of three
      factors, initial glucose concentration (0 and 9 g/L), agitation (100 and 180
      rpm), and pH (3.0 and 5.0), were evaluated to identify the significant effects
      and its interactions in the laccase production. The pH of the medium was found to
      be the most important factor, followed by initial glucose concentration and the
      interaction of both factors. Agitation did not seem to play an important role in
      laccase production, nor did the interaction agitation x medium pH and agitation x
      initial glucose concentration. Response surface analysis showed that an initial
      glucose concentration of 11 g/L and pH controlled at 5.2 were the optimal
      conditions for laccase production by T. versicolor. Under these conditions, the
      predicted value for laccase activity was >10,000 U/L, which is in good agreement
      with the laccase activity obtained experimentally (11,403 U/L). In addition, a
      mathematical model for the bioprocess was developed. It is shown that it provides
      a good description of the experimental profile observed, and that it is capable
      of predicting biomass growth based on secondary process variables.

PMID- 16960283
TI  - Culture pH affects exopolysaccharide production in submerged mycelial culture of
      Ganoderma lucidum.
AB  - In submerged culture of Ganoderma lucidum, the pH optimum for cell growth has
      been shown to be lower than that for exopolysaccharides (EPS) formation.
      Therefore, in the present study, a two-stage pH-control strategy was employed to
      maximize the productions of mycelial biomass and EPS. When compared, a batch
      culture without pH control had a maximum concentration of EPS and
      endopolysaccharides, which was much lower than those with pH control. Maximum
      mycelial growth (12.5 g/L) and EPS production (4.7 g/L) were achieved by shifting
      the controlled pH from 3.0 to 6.0 after day 4. The contrast between the
      controlled-pH process and uncontrolled pH was marked. By using various two-stage
      culture processes, it was also observed that culture pH has a significant affect
      on the yield of product, mycelial morphology, chemical composition, and molecular
      weight of EPS. A detailed observation of mycelial morphology revealed that the
      productive morphological form for EPS production was a dispersed pellet
      (controlled pH shifting from 3.0 to 6.0) rather than a compact pellet with a
      dense core area (controlled pH 4.5) or a feather-like pellet (controlled pH
      shifting from 6.0 to 3.0). Three different polysaccharides were obtained from
      each pH conditions, and their molecular weights and chemical compositions were
      significantly different.

PMID- 16960284
TI  - Simultaneous saccharification and fermentation of cassava bagasse for L-(+)
      lactic Acid production using Lactobacilli.
AB  - Saccharification and fermentation of cassava (Manihot esculenta) bagasse was
      carried out in a single step for the production of L-(+)-lactic acid by
      Lactobacillus casei and Lactobacillus delbrueckii. Using 15.5% w/v of cassava
      bagasse as the raw material, a maximum starch to lactic acid conversion of 96%
      was obtained with L. casei with a productivity rate of 1.40 mg/mLxh and maximum
      yield of 83.8 mg/mL. It was 94% with L. delbrueckii with a productivity rate of
      1.36 mg/mLxh and maximum yield of 81.9 mg/mL. Supplementation of bagasse with
      0.01% w/v MnCl2 showed positive influence on the lactic acid production by L.
      casei.

PMID- 16960285
TI  - Ethanol production from dilute-Acid softwood hydrolysate by co-culture.
AB  - Dilute-acid softwood hydrolysate, with glucose and xylose as the dominant sugars,
      was fermented to ethanol by co-cultures. The strains used include Saccharomyces
      cerevisiae 2.535 (1#), Pachysolen tannophilis ATCC 2.1662 (2#), and recombinant
      Escherichia coli (3#) constructed in our laboratory carrying both pdc and adhB
      genes derived from Zymomonas mobilis. Before fermentation, the co-cultures were
      adapted for five batches. Observation under light microscope showed aggregation
      of adapted strains, which could possibly improve their ability to degrade
      inhibitors. In addition, we tried to detoxify the dilute-acid softwood
      hydrolysate with a combined method before fermentation. Our study showed that
      fermentation of detoxified hydrolysate by adapted co-culture (1# + 2#) generated
      an exceptionally high ethanol yield on total sugar of 0.49 g/g, corresponding to
      96.1% of the maximal theoretical value after 48 h; fermentation of detoxified
      hydrolysate by adapted co-culture (1# + 3#) is faster (24 h) and could reach a
      high ethanol yield (0.45 g/g total sugar). These experiments suggest that both
      adaptation and detoxification significantly improve hydrolysate fermentation and
      ethanol production.

PMID- 16960286
TI  - The life-saving properties of blood: mitigating cerebral insult after traumatic
      brain injury.
AB  - Transfusion of packed red blood cells in critically injured patients has been a
      lifesaving (although not completely benign) intervention for decades. The
      traumatically injured brain has been thought to be particularly susceptible to
      injury from anemia, due to the well-documented association of worsening mortality
      and functional outcome in the presence of hypotension and hypoxia, as well as the
      known vulnerability of many neuronal populations to ischemia. Red blood cell
      transfusion has been used in traumatic brain injury (TBI) to prevent cerebral
      ischemia by maximizing the oxygencarrying capacity of blood that is otherwise
      decreased by blood loss and dilution with crystalloid fluid replacement during
      resuscitation. Although many practitioners have commonly utilized hemoglobin
      (Hgb) or hematocrit thresholds for transfusion in these patients, the rationale
      for this practice has largely been centered on older studies in general critical
      care populations and animal evidence. Furthermore, in addition to an ideal "
      target " Hgb, many other questions remain about this clinical practice, such as
      the optimal duration of maintaining a specific Hgb level, and the ultimate
      effects of transfusion on neurological and functional outcome.

PMID- 16960287
TI  - Effect of a liberal versus restrictive transfusion strategy on mortality in
      patients with moderate to severe head injury.
AB  - OBJECTIVE: To compare a restrictive versus a liberal transfusion strategy in
      patients with moderate to severe closed head injury following multiple trauma in
      13 Canadian intensive care units (ICUs). METHODS: This is a subgroup analysis of
      a multicenter randomized controlled clinical trial involving sixty-seven
      critically ill patients from the Transfusion Requirements in the Critical Care
      trial who sustained a closed head injury. Patients had a hemoglobin concentration
      less than 9.0 g/dL within 72 hours of admission to the ICU. Patients were
      randomized to a restrictive allogeneic red blood cell transfusion strategy
      (hemoglobin 7.0 g/dL and maintained between 7.0 and 9.0 g/dL) or a liberal
      strategy (hemoglobin 10.0 g/dL and maintained between 10.0 and 12.0 g/dL).
      RESULTS: Baseline characteristics in the restrictive ( n = 29) and the liberal (
      n = 38) transfusion groups were comparable. Average hemoglobin concentrations and
      red blood cell units transfused per patient were significantly lower in the
      restrictive compared to the liberal group. The 30-day all-cause mortality rates
      in the restrictive group were 17% as compared to 13% in the liberal group (risk
      difference 4.1 with 95% confidence interval [CI], 13.4 to 21.5, p = 0.64).
      Presence of multiple organ dysfunction (12.1 +/- 6.4 versus 10.6 +/- 6.3, p =
      0.35) and changes in multiple organ dysfunction from baseline scores adjusted for
      death (4.5 +/- 6.2 versus 3.4 +/- 6.2, p = 0.49) were similar between the
      restrictive and liberal transfusion groups, respectively. Median length of stay
      in ICU (10 days, interquartile range 5 to 21 days versus 8 days, interquartile
      range 5 to 11 days, p = 0.26) and hospital (27 days, interquartile range 14 to 39
      days versus 30.5 days, interquartile range 17 to 47 days, p = 0.72) were similar
      between the restrictive and liberal transfusion groups. CONCLUSIONS: We were
      unable to detect significant improvements in mortality with a liberal as compared
      to restrictive transfusion strategy in critically ill trauma victims with
      moderate to severe head injury.

PMID- 16960288
TI  - Brain temperature and outcome after severe traumatic brain injury.
AB  - INTRODUCTION: In humans, raised body temperature is linked to poor outcome after
      brain injury. Because deviations between brain and body temperature have been
      reported after severe traumatic brain injury (TBI), the aim of this study was to
      explore the relationship between initial and mean brain temperature and survival
      at 3 months. METHODS: Intraparenchymal temperature was measured 3 - 4 cm within
      white matter. Logistic regression was used to explore linear and quadratic
      relationships between initial and average brain temperature and survival at 3
      months. RESULTS: In 36 patients, initial brain temperatures ranged from 33.5 to
      39.2 degrees C (median 37.4 degrees C). There was no evidence of an association
      between initial brain temperature and risk of death, either linear (odds ratio
      [OR] 95% confidence interval [CI] = 1.3 [0.68 to 2.5], p = 0.42) or quadratic ( p
      = 0.26). Assuming a linear relationship, patients with higher mean brain
      temperatures were less likely to die: OR (95% CI) for death per 1 degrees C was
      0.31 (0.09 to 1.1), p = 0.06. However, by fitting the quadratic relationship,
      there was a suggestion that both high and low temperatures were associated with
      increased risk of death: p = 0.06. CONCLUSION: Initial brain temperature measured
      shortly after admission did not predict outcome. There is a suggestion that
      patients with "middle range" temperatures were less likely to die.

PMID- 16960289
TI  - Surgery for patients with severe supratentorial intracerebral hemorrhage.
AB  - INTRODUCTION: Little information is available on the efficacy of aggressive
      treatment such as surgery in improving the outcome of severely affected patients
      after supratentorial intracerebral hemorrhage (ICH). Our objective was to assess
      the effect of hematoma removal and ventricular drainage on the mortality of
      patients with severe primary supratentorial ICH. METHODS: We studied 103
      consecutive patients who were admitted to the intensive care unit and diagnosed
      with primary supratentorial ICH. The impacts of clinical factors on 30-day
      mortality were assessed, including surgery, Glasgow Coma Scale (GCS) score and
      pupillary abnormality at admission, hematoma volume, and other related factors.
      RESULTS: The 30-day mortality rate was 42%, and the median time between admission
      and death was 3 days (range: 1 to 27 days). Hematoma removal and ventricular
      drainage, within the first 24 hours of admission, were performed on 11 and 17
      patients, respectively. Two patients who were treated with removal and four with
      drainage died. A logistic regression model for predicting 30-day mortality was
      performed. After controlling for GCS score, pupillary abnormality, hydrocephalus,
      and hematoma volume, hematoma removal was identified as an independent predictor
      of survival (odds ratio [OR], 0.12; 95% confidence interval [CI], 0.02 to 0.92).
      Ventricular drainage also tended to decrease mortality rate greatly (OR, 0.31;
      95% CI, 0.06 to 1.76). Patients with GCS scores of 3 or 4 were 4.01 times more
      likely to die (95% CI, 1.13 to 14.26) than those with GCS of at least 5.
      CONCLUSIONS: Hematoma removal may reduce the mortality rate of patients with
      severe supratentorial ICH.

PMID- 16960290
TI  - Ventriculo-lumbar perfusion in acute ischemic stroke.
AB  - INTRODUCTION: Effective treatment for severe ischemic stroke continues to be
      largely an unmet medical need. Using a nonvascular (paravascular cerebrospinal
      fluid) pathway to provide oxygen and nutrients to ischemic tissues may be a means
      of treating this disease. The primary objective of this study was to evaluate the
      safety and technical feasibility of ventriculo-lumbar perfusion with the
      oxygenated fluorocarbon nutrient emulsion (OFNE) perfusion system in the
      treatment of patients with severe hemispheric cerebral ischemia. RESULTS: Four
      patients were enrolled in this pilot study. At admission, patients' National
      Institutes of Health Stroke Scale scores ranged from 16 to 24. The perfusion
      pathway was successfully established in all four patients. Maximum perfusion
      rates varied from 25 to 40 mL/minute; total volume perfused over the 24-hour
      period ranged from 30.6 to 45.8 L. ICP ranged from -3 to 16 mmHg during the
      perfusion. The 24-hour perfusion was successfully completed in all four patients
      with no serious adverse events during the perfusion. CONCLUSION: It is
      technically feasible and safe to establish a ventriculo-lumbar perfusion pathway
      using a specially designed lumbar drainage catheter and to control intracranial
      pressure while perfusing large volumes of OFNE.

PMID- 16960291
TI  - Cerebellar hemorrhage caused by remote neurological surgery.
AB  - INTRODUCTION: Intracranial hemorrhage usually occurs as a complication of
      hypertension, coagulopathy, or trauma. In rare instances, remote cerebellar
      hemorrhage (RCH) may complicate supratentorial or spinal surgery. METHODS:
      Retrospective case series study. RESULTS: We describe three cases of RCH
      complicating spinal and cranial surgical procedures associated with cerebrospinal
      fluid hypotension. CONCLUSIONS: Remote cerebellar intracranial hemorrhage may
      complicate neurosurgical procedures in which cerebrospinal fluid hypotension
      occurs.

PMID- 16960292
TI  - Paradoxically accelerated fatal brain herniation following thrombolytic therapy
      in acute ischemic stroke.
AB  - INTRODUCTION: The use of plasminogen activators (PAs) in acute stroke patients
      has dual effects. PAs are beneficial by dissolving thrombi occluding an artery,
      but may be harmful by their proteolytic and excitotoxic actions. METHODS AND
      RESULTS: We report two patients with a fatal brain herniation who rapidly
      deteriorated despite the successful recanalization and the sustained arterial
      patency or blood flow. Imaging studies taken after the thrombolytic treatment
      suggested early occurrence of cellular damage and profound breakdown of the blood
      brain barrier. CONCLUSION: Fatal brain edema occurred after persistent
      reperfusion by the thrombolytic therapy. Paradoxical thrombolytic-induced injury,
      which has been suggested in experimental studies, might play a role.

PMID- 16960294
TI  - A sinister cause of nausea and vomiting.
AB  - A 30-year-old intellectually challenged woman with recent travel history to Texas
      presented with intractable nausea and nonprojectile vomiting for 3 weeks. She had
      diffuse abdominal pain with no change in her bowel movements. Her family noted
      that she had recently become more withdrawn. On presentation, she was afebrile
      with a normal abdominal exam. Physical examination was remarkable for subtle
      bilateral end-gaze nystagmus. An extensive workup at an outside hospital over 2
      weeks included upper endoscopy with small bowel follow-through, pelvic sonogram,
      and a head computed tomography (CT), all of which were reportedly unremarkable.
      No outside films were accessible at the time. At our facility, laboratory
      examination was obtained that ruled out an infectious etiology. Abdominal CT
      showed no gastrointestinal or hepatobiliary abnormalities. Because of reported
      personality changes and nystagmus on physical exam, magnetic resonance imaging
      (MRI) of the head was obtained to rule out cerebellar or vestibular pathology.

PMID- 16960293
TI  - Acute subdural hematoma caused by an unruptured, thrombosed giant intracavernous
      aneurysm.
AB  - INTRODUCTION: Acute subdural hematoma (SDH) is an infrequent complication after
      aneurysmal subarachnoid hemorrhage. SDH associated with unruputed intracavernous
      aneurysm has never been reported. METHODS: Single patient case report and review
      of relevent literature. RESULTS: A 65-year-old woman with an unruptured,
      thrombosed giant intracavernous aneurysm developed an acute SDH 2 days after
      admission for cavernous sinus syndrome. Despite emergent evacuation of the SDH,
      the patient never regained consciousness because of brain herniation. CONCLUSION:
      Acute SDH is a rare complication of ruptured, giant intracavernous aneurysms.
      Erosion of the cavernous sinus wall by acute enlargement of the aneurysm after
      thrombosis is the proposed mechanism for development of the SDH.

PMID- 16960295
TI  - Computed tomography findings in thiamine deficiency-induced coma.
AB  - Although brain magnetic resonance imaging is a more sensitive diagnostic tool in
      the evaluation of coma, noncontrast head computed tomography (CT) may demonstrate
      highly specific findings in some cases of coma. We present a case of thiamine
      deficiency-induced coma associated with acute necrosis of fornices documented on
      CT and review cardinal neuroimaging features of Wernicke encephalopathy. Acute
      fornices necrosis is a novel finding on head CT suggestive of thiamine
      deficiency.

PMID- 16960296
TI  - Pneumocephalus secondary to lumbar catheterization.
AB  - A 60-year-old woman with a history of chronic back pain presented to the
      emergency department with headache, slurred speech, and altered sensorium
      reported by her family. The previous day, she had a lumbar catheter placed for
      symptomatic relief of her chronic back pain. The patient complained only of
      headache, but otherwise thought she was unaffected. The patient's past medi- cal
      history was remarkable for diabetes, hypertension, peripheral neuropathy,
      gastritis, supraventricular tachycardia, and chronic back pain. On physical
      examination she was alert, fully orientated, and in no acute distress. Her vital
      signs were normal. Neurological examination revealed subtle word-finding
      difficulties and dysarthria. There were no physical signs of raised intracranial
      pressure (ICP). The remainder of her examination was entirely normal.

PMID- 16960297
TI  - Erroneous intracranial pressure measurements from simultaneous pressure
      monitoring and ventricular drainage catheters.
AB  - The objective of this report is to highlight the potential for false pressure
      measurements from systems that combine intracranial pressure (ICP) measurement
      and ventricular drainage. If the ports of the drain become blocked to the extent
      that they present a high resistance to cerebrospinal fluid flow, then a
      significant pressure gradient between the inside and outside of the catheter may
      be established. Thus, any intracatheter transducer will faithfully record a
      pressure much lower than true ICP. This holds true for catheter-tip transducers
      when the transducer lies inside the catheter. In the absence of flow, however,
      pressures will equalize; therefore, accurate measurements may be taken if the
      drain is temporarily closed. We model this situation and provide simulations of
      expected measurements in such situations; these compare well to observed clinical
      readings.

PMID- 16960298
TI  - Clinical implications of quantitative infrared pupillometry in neurosurgical
      patients.
AB  - Pupillometry has been widely employed in the evaluation of a large number of
      pathological conditions, including intracranial pathology. The recent
      introduction of a portable, user-friendly, infrared pupillometer (ForSite,
      NeurOptics Inc., Irvine, CA) has enabled the accurate and reproducible
      measurement of several pupillary parameters, such as maximum and minimum
      apertures, constriction and dilation velocities, and latency period. It should be
      noted that various clinical conditions, especially neurological and ocular
      diseases, as well as numerous medications, may interfere with the measurements.
      Furthermore, a number of physiological parameters, such as the intensity of
      retinal illumination, the level of patient's alertness, the intensity of ambient
      light, as well as the time of day that the examination is performed may alter the
      obtained values. The potential implications of pupillometry in the clinical
      assessment of neurosurgical patients, including its complex relationship to
      intracranial pressure changes, mandate the undertaking of prospective clinical
      studies validating the clinical significance of this noninvasive, diagnostic
      modality.

PMID- 16960299
TI  - Endocrine failure after traumatic brain injury in adults.
AB  - OBJECTIVE: To review histopathological and clinical data linking endocrine
      failure to traumatic brain injury (TBI) during acute neurosurgical treatment and
      rehabilitation. METHODS: A focused search of the Medline (PubMed) medical
      literature database and the authors' files were used to identify selected
      publications. RESULTS: Endocrine failure may produce clinically important
      consequences during acute and convalescent care after TBI, and may be caused by
      direct injury to the hypothalamic- pituitary axis (HPA), neuroendocrinological
      effects from catecholamines and cytokines, or from systemic
      infection/inflammation that produces primary gland failure. Autopsy evidence of
      hemorrhage or ischemia in the HPA is common soon after TBI. The estimated
      incidence of acute hormone reduction is adrenal 15%, thyroid 5 - 15%, growth
      hormone 18%, vasopressin 3 - 37%, and gonadal (25 - 80%). Hyperprolactinemia
      occurs in more than 50% of patients. Inappropriate secretion of antidiuretic
      hormone (SIADH) and the euthyroid sick syndrome are common. Acute adrenal
      failure, central hypothyroidism, SIADH, and diabetes insipidus (DI) may cause
      poor neurological outcomes including death, hypo/hypernatremia, hypotension, and
      increased vasoactive drug requirements. Treatment of those conditions is
      warranted. Delayed diagnosis of hypopituitarism is often mistaken for symptoms of
      residual head injury. Some chronic hormone deficiency occurs in 30 - 40% of
      selected patients after TBI, more than one deficiency in 10 - 15%, growth hormone
      in 15 - 20%, gonadal hormones in 15%, and hypothyroidism in 10 - 30%. Chronic
      adrenal failure and DI are reported over a wide incidence. Prolactin is elevated
      in 30%. All clinical symptoms respond favorably to replacement therapy.
      CONCLUSIONS: Severe TBI associated with basilar skull fracture, hypothalamic
      edema, prolonged unresponsiveness, hyponatremia, and/or hypotension is associated
      with a higher occurrence of endocrinopathy. Greater awareness of this possible
      complication of TBI and appropriate testing are encouraged.

PMID- 16960300
TI  - Levetiracetam is neuroprotective in murine models of closed head injury and
      subarachnoid hemorrhage.
AB  - OBJECTIVES: Prophylactic treatment with antiepileptic drugs is common practice
      following subarachnoid hemorrhage (SAH) and traumatic brain injury. However,
      commonly used antiepileptic drugs have multiple drug interactions, require
      frequent monitoring of serum levels, and are associated with adverse effects that
      may prompt discontinuation. In the current study, we test the hypothesis that
      levetiracetam, an anticonvulsant with favorable interaction and adverse event
      profiles, is neuroprotective in clinically relevant models of SAH and closed head
      injury (CHI). METHODS: A single intravenous dose of vehicle, low-dose (18 mg/kg),
      or high-dose (54 mg/kg) levetiracetam was administered intravenously followed
      CHI. Functional assessments were performed on a daily basis, and histological
      assessments performed at 24 hours. In a separate series of experiments, mice were
      randomized to receive intravenous administration of vehicle, low-dose, or high
      dose levetiracetam every 12 hours for 3 days following SAH. Functional endpoints
      were assessed daily, followed by measurement of MCA luminal diameter on day 3.
      RESULTS: A single dose of levetiracetam improved functional and histological
      outcomes after CHI. This effect appeared specific for levetiracetam and was not
      associated with fosphenytoin treatment. Treatment with levetiracetam also
      improved functional outcomes and reduced vasospasm following SAH. CONCLUSION:
      Levetiracetam is neuroprotective in clinically relevant animal models of SAH and
      CHI. Levetiracetam may be a therapeutic alternative to phenytoin following acute
      brain injury in the clinical setting when seizure prophylaxis is indicated.

PMID- 16960303
TI  - The evolutionary psychology of obsessive-compulsive disorder: the role of
      cognitive metarepresentation.
AB  - Repetitive unpleasant thoughts and ritualized behaviors are the key features of
      obsessive-compulsive disorder (OCD). The classical neuroethological models of OCD
      rely largely on behavioral similarities between animal stereotypies and human
      compulsive rituals and are unable to account for the cognitive component of OCD.
      The cognitive symptoms of OCD need to be addressed in an evolutionary
      psychological context that incorporates information about human brain evolution.
      OCD can be understood as an extreme on a continuum of evolved harm-avoidance
      strategies. A pathological exaggeration of our evolved capacity to cognitively
      represent future scenarios, including imagined consequences of our own thoughts
      and actions (metarepresentation), may be part of the set of evolved psychological
      mechanisms contributing to the psychopathology of OCD. The costly side of the
      adaptive ability to anticipate future needs or threats could be that
      etiologically heterogeneous affections of the underlying striatal-frontal brain
      circuits may render an individual vulnerable to develop OCD.

PMID- 16960304
TI  - Medical electricity and madness in the 18th century: the legacies of Benjamin
      Franklin and Jan Ingenhousz.
AB  - Benjamin Franklin had at least two accidents that resulted in electricity passing
      through his brain. In addition, he witnessed a patient's similar accident and
      performed an experiment that showed how humans could endure shocks to the head
      without serious ill effects, other than amnesia. Jan Ingenhousz, Franklin's Dutch
      born medical correspondent better known for his discovery of photosynthesis, also
      had a serious accident that sent electricity though his head and, in a letter to
      Franklin, he described how he felt unusually elated the next day. During the
      1780s, Franklin and Ingenhousz encouraged leading French and English electrical
      "operators" to try shocking the heads of melancholic and other deranged patients
      in their wards. Although they did not state that they were responding to
      Ingenhousz's and Franklin's suggestions, Birch, Aldini, and Gale soon did
      precisely what Ingenhousz and Franklin had suggested. These practitioners did not
      appear to induce convulsions in their mentally ill patients, but they still
      reported notable successes.

PMID- 16960305
TI  - Heart attacks, heart rate, and gel electrodes: the invention of ambulatory
      cardiology.
AB  - Ambulatory cardiology began in 1959 in a department of pathology to answer a
      question raised at the autopsy table: are high heart rates in apparently healthy
      individuals a risk factor for developing coronary artery disease? This question
      led to the development of a miniature monitor and a new kind of electrode, which
      enabled clinicians to measure EKG signals during activity and over prolonged
      periods of time. These electrodes are now used universally for diagnosis and for
      monitoring the heart during a myriad of different activities and circumstances.
      The story of the development of the monitor and electrodes illustrates the ways
      in which ideas and discovery lead to applications and advances in medicine.

PMID- 16960306
TI  - Environment, population, and biology: a short history of modern epidemiology.
AB  - Since its origin in the 19th century, epidemiology has faced an internal tension
      between an approach oriented toward biology and the study of mechanisms, and an
      approach oriented toward populations and their interactions with the environment.
      Initially, this tension took the form of an opposition between microbiology and
      statistics. We describe the early roots of the quantitative approach to health
      and disease and several historical examples of the above tension. The search for
      the causes of pellagra exemplifies our thesis. In Italy, where pellagra was
      endemic, contrasting opinions coexisted between the hypothesis of contaminated
      maize, supported by Cesare Lombroso, and the hypothesis of a prevailing role of
      poverty and poor nutrition. In the United States, Joseph Goldberger found no
      evidence for the hypothesis of contaminated maize or for a microbiological agent,
      but recognized the central role of nutrition. The "cure" Goldberger proposed was
      land reform, but he continued studying the disease from a mechanistic point of
      view; shortly after his death, niacin deficiency was identified as the cause of
      pellagra. The tension between mechanistic and population-based studies is still
      present within epidemiology and is in fact essential for the success of the
      discipline.

PMID- 16960307
TI  - Aristotle's study of the animal world: the case of the kobios and phucis.
AB  - Aristotle was a remarkable observer of the living world. He made detailed
      observations on the anatomy and life history characteristics of many organisms as
      part of a larger study into the differentiae (diaphora) of groups of animals.
      This reexamination of Aristotle's observations of two small fishes is a study
      into the work or the way of being of particular organic wholes. As such, it is
      directed by three main objectives: to evaluate the accuracy of those observations
      Aristotle makes with regard to the kobios and phucis in the History of Animals,
      as well as to understand how he might have conducted his research; to determine
      whether aspects of those observations would ground more philosophical arguments;
      and to contribute to the understanding of the basic biology of these fishes. In
      so doing, this article also may introduce a new generation of biologists to the
      richness of Aristotle's biological observations and the questions that motivated
      them.

PMID- 16960308
TI  - "Aequanimitas" Redux: William Osler on detached concern versus humanistic
      empathy.
AB  - Recent critics make William Osler "the father of cool detachment" in medicine,
      largely because of his "Aequanimitas" address emphasizing objectivity and
      imperturbability. Closer analysis suggests that Osler's aequanimitas resembles
      more nearly the metriopatheia of later Stoic philosophy than the apatheia of the
      early Stoics. A previously unpublished memoir clarifies at least in part Osler's
      motive for teaching control of the "medullary centres" to minimize facial
      expression: he did not want to frighten patients, who typically had serious
      illnesses for which he lacked effective therapy. Twenty-first century challenges
      to medicine as a profession differ substantially from those of Osler's era.
      Physicians and educators must focus more closely on the tension between detached
      concern ("competence") and humanistic empathy ("caring") if medicine is to thrive
      as a learned profession as opposed to a technical service, a commodity to be
      bought and sold like any other.

PMID- 16960309
TI  - Doctoring as leadership: the power to heal.
AB  - Physician power has been attacked, and tabooed, in legitimate efforts to
      strengthen patients' rights. Yet the structural and symbolic power wielded by
      doctors is what makes good and right healing actions possible. Avoiding the power
      issue contributes to a confusing state, where patient trust is faltering and
      physicians are uncertain about how to fulfill the doctor's role with the
      intellectual tools of mere science and technology. I argue that constitutive
      characteristics of health, illness, and the clinical encounter necessitate a
      prescriptive and responsible healing agent who is more than a technocrat, an
      information broker, or a seller. The article proposes clinical leadership as a
      concept offering practical and ethical direction to clinicians, education,
      research, and health policy. Leadership presupposes reflective awareness of
      physicians' structural and symbolic power, and is displayed as discerning,
      empowering improvisations in critical situations, based on empathy and
      willingness to learn from patients. The notion of clinical leadership highlights
      patient vulnerability, medicine's ethical core, and the importance of character
      development in medical education.

PMID- 16960311
TI  - What's in a Name? Death before birth.
AB  - The medical, legal, and lay communities utilize a range of words to describe a
      pregnancy that does not result in live birth. These terms, including abortion,
      miscarriage, and stillbirth, are more than just words: they carry with them a
      range of meanings and social consequences. This paper explores the complex
      implications embodied in the language used to designate fetal death and describes
      how they simultaneously, and paradoxically, establish conflicting subject
      positions for mother and fetus. It also examines the statutory regulations that
      affirm the problematic terms in a manner that may leave grieving families without
      ritual outlets for the expression of their loss. This paper draws on specific
      examples from Aotearoa New Zealand, while recognizing similarities across Western
      cultures.

PMID- 16960310
TI  - Contested boundaries: psychiatry, disease, and diagnosis.
AB  - Since the 19th century, we have come to think of disease in terms of specific
      entities--entities defined and legitimated in terms of characteristic somatic
      mechanisms. Since the last third of that century, we have expanded would-be
      disease categories to include an ever-broader variety of emotional pain,
      idiosyncrasy, and culturally unsettling behaviors. Psychiatry has been the
      residuary legatee of these developments, developments that have always been
      contested at the ever-shifting boundary between disease and deviance, feeling and
      symptom, the random and the determined, the stigmatized and the value-free. Even
      in our era of reductionist hopes, psychopharmaceutical practice, and corporate
      strategies, the legitimacy of many putative disease categories will remain
      contested. The use of the specific disease entity model will always be a
      reductionist means to achieve necessarily holistic ends, both in terms of
      cultural norms and the needs of suffering individuals. Bureaucratic rigidities
      and stakeholder conflicts structure and intensify such boundary conflicts, as do
      the interests and activism of an interested lay public.

PMID- 16960312
TI  - The rise and demise of a collection of human fetuses at Mount Holyoke College.
AB  - When I found myself at the center of a controversy over the disposition of an old
      collection of human fetal specimens at Mount Holyoke College, I was motivated to
      explore the historical transformation that turned embryo collecting for research
      and pedagogical purposes from a noble to a disparaged practice, and dead fetuses
      from prized anatomical specimens to ugly, anomalous entities. Using Linda Layne's
      analysis of the literal and symbolic erasure of dead fetuses from American
      cultural discourse, this article examines the shifting circumstances that once
      encouraged the collection of fetal specimens but that now mandate their
      disappearance. Using Mount Holyoke as a case study, it describes the scientific
      logic and specific social exchange networks that led to the acquisition of
      hundreds of fetal specimens in the first half of the 20th century. It also
      examines the factors--including changes in biology education, concerns about
      handling hazardous fixatives, and especially the prominence of beautified and
      lifelike fetal images consistent with the so-called "culture of life"--that
      prompt the dissolution and demise of human embryo and fetal collections.

PMID- 16960314
TI  - A dietician's perspective on diabetes among migrant farmworkers.

PMID- 16960315
TI  - Balancing service and education: ethical management of student-run clinics.
AB  - At medical schools across the United States, students operate free clinics that
      have the potential to provide health benefits to patients while furnishing unique
      educational opportunities for students. While they provide the energy necessary
      to make these clinics successful, students must, due to their inexperience,
      collaborate with faculty, clinic preceptors, community members and medical school
      administrators to ensure that their clinics attain high standards in health care
      and education. Medical school faculty and clinic preceptors must make certain
      that appropriate health care is provided and that desirable educational messages
      regarding physician professionalism and altruism are conveyed effectively. As
      faculty availability in such clinics is limited, it is important that the pursuit
      of educational goals not compromise clinics' patient care. By valuing faculty
      time dedicated to this work and actively supporting clinic organizers'
      applications for external funding, medical school administrators can facilitate
      high quality care and education at student-run clinics.

PMID- 16960316
TI  - Training welfare caseworkers in service excellence: increasing children's
      Medicaid coverage.
AB  - Many low-income children who are eligible for public sector health insurance
      remain uninsured. There are many barriers to enrolling these children, but one
      key issue is parents' reluctance to use the services of the local enrollment
      agency, which is usually the welfare office. The Eastside Access Partnership, a
      community-academic coalition on the Eastside of Detroit, addressed the problem of
      uninsured-but-eligible children through a variety of interventions focused on (1)
      enhancing community members' understanding of the enrollment process and (2)
      reducing institutional barriers to enrollment. One of these interventions
      addressed the institutional barriers by developing a customer service excellence
      training program for welfare caseworkers. The training program curriculum, which
      was developed following the principles of community-based participatory research,
      included extensive input from community residents, welfare agency staff, and
      academic researchers. The training sessions received positive evaluations from
      participants and agency executives. A more thorough evaluation of the project is
      under way.

PMID- 16960302
TI  - Airborne environmental injuries and human health.
AB  - The concept that the environment in which we live can have detrimental effects on
      our health has existed for centuries. Obvious examples of substances that can
      cause human diseases include infectious agents, poisons, chemicals and other
      noxious agents, drugs, and physical stimuli such as bright lights and loud
      sounds. Some less obvious agents can include allergens, nontangible agents such
      as colorless, odorless gases and aerosolized toxins. In recent decades, humans
      have developed various new materials and compounds. Additionally, we are now
      producing known compounds, and even naturally occurring substances, in vastly
      increased amounts. Many of these substances are generally believed to threaten
      the health of our environment. However, there is also a considerable amount of
      hype and exaggeration regarding some of these agents (e.g., mold) that is
      unsubstantiated. This article extensively reviews the data on a large number of
      airborne-related illnesses and attempted to place scientific reality in the
      context of clinical medicine.

PMID- 16960318
TI  - Health literacy among English-speaking parents in a poor urban setting.
AB  - We surveyed English-speaking parents attending an inner-city health center.
      Subjects read the label on a bottle of liquid medicine and 1) demonstrated how
      much medicine they should give, 2) stated how many times a day they should give
      the medicine, and 3) stated when they should give the next dose. We calculated
      adjusted odds ratios to test for the likelihood of incorrect medication dosing
      for subjects with and without demographic risk factors. Three hundred twenty six
      subjects participated. Overall, 252 (77%) demonstrated incorrect medication
      dosing. Medication dosing was more likely to be incorrect among young parents
      (AOR 2.45; CI 1.14, 5.26), immigrants (AOR 2.27; CI 1.04, 4.96), subjects without
      a high school degree (AOR 2.05; CI 1.04,4.05), and those who did not recall ever
      having been shown how to use a medicine dropper (AOR 1.79; CI 1.01,3.19).
      Implications for practice are discussed.

PMID- 16960317
TI  - Elevated risk of death for African Americans with AIDS, San Francisco, 1996-2002.
AB  - Disparities in survival among people with AIDS continue in the treatment era,
      with a higher rate of death among African Americans than among Whites, Latinos,
      and Asians/Pacific Islanders (API). Few studies have been able to identify
      underlying reasons for this disparity. The authors' objectives were to determine
      the extent of disparities in AIDS-related death by race/ethnicity, and examine
      factors that may contribute to or explain these differences. Using San Francisco
      surveillance data, racial/ethnic differences in survival among residents
      diagnosed with AIDS between 1996 and 2002 were analyzed using Kaplan-Meier
      survival and Cox proportional hazards regression techniques. The data confirm
      that a disparity in survival after AIDS persists between African Americans and
      Whites, Latinos, and APIs in San Francisco. Underlying causes of this disparity
      are multiple, but many of them are amenable to intervention and should be
      addressed.

PMID- 16960319
TI  - Breaking down barriers to breast and cervical cancer screening: a university
      based prevention program for Latinas.
AB  - INTRODUCTION: The lower rate of utilization of mammography and cervical cancer
      screening observed for Latinas in the United States has been attributed to
      cultural, economic, and linguistic barriers they may encounter. METHODS: A
      screening program was implemented offering cancer prevention education plus
      breast and cervical cancer screening to Latinas, as well as all necessary follow
      up care, at no cost to the participant. RESULTS: In the first 6 years of this
      project, a total of 928 screening visits occurred; 53% were participants who had
      returned at least once for additional annual screening. Ninety-one percent of
      participants preferred speaking in Spanish to their health care providers;
      however, only 2% identified a primary care provider and 5% stated they had health
      care insurance. The participant characteristics and results of initial
      evaluation, as well as necessary follow-up studies, are presented. CONCLUSIONS:
      By removing economic concerns and by providing care and education through
      bilingual staff in a culturally sensitive environment, some of the barriers to
      cancer screening for Latinas were overcome. The success of the program is
      reflected by a high rate of return for additional annual screening by our
      participants.

PMID- 16960320
TI  - Using mail to reach patients seen at an urban health care facility.
AB  - Urban American Indians/Alaska Natives (AI/ANs) are highly mobile, and little is
      known about ways to include them in research or clinical activities. We evaluated
      postal mailings as a means of reaching patients seen at an urban Indian health
      care facility (60% of whom were AI/AN) and identified factors associated with
      receipt of mail. As part of a clinical trial, a Native art calendar was sent via
      first class mail to 5,633 clients seen at the urban Indian clinic during the
      prior two years. A multi-step address verification process was conducted,
      including telephone contacts, Web searches, and in-person visits. Logistic
      regressions examined the association of client characteristics with accurate
      addresses. Based on initial mailings and in-person location efforts, we estimated
      that only 61% of clients actually received the calendars. The multi-step address
      verification process was significantly less likely to identify working addresses
      for clients who were AI/AN and clients who were seen more than 3 months before
      the study. Reaching urban AI/ANs for research activities and health care is
      difficult. Innovative strategies are needed to locate this highly mobile and
      understudied population.

PMID- 16960321
TI  - Urban-rural differences in excess mortality among high-poverty populations:
      evidence from the Harlem Household Survey and the Pitt County, North Carolina
      Study of African American Health.
AB  - Black youth residing in high-poverty areas have dramatically lower probabilities
      of surviving to age 65 if they are urban than if they are rural. Chronic disease
      deaths contribute heavily. We begin to probe the reasons using the Harlem
      Household Survey (HHS) and the Pitt County, North Carolina Study of African
      American Health (PCS). We compare HHS and PCS respondents on chronic disease
      rates, health behaviors, social support, employment, indicators of health care
      access, and health insurance. Chronic disease profiles do not favor Pitt County.
      Smoking uptake is similar across samples, but PCS respondents are more likely to
      quit. Indicators of access to health care and private health insurance are more
      favorable in Pitt County. Findings suggest rural mortality is averted through
      secondary or tertiary prevention, not primary. Macroeconomic and health system
      changes of the past 20 years may have left poor urban Blacks as medically
      underserved as poor rural Blacks.

PMID- 16960322
TI  - Can non-medical factors contribute to disparities in coronary heart disease
      treatments?
AB  - Racial/ethnic and sex disparities in coronary heart disease treatment exist. We
      previously reported that physicians perceive non-clinical variables, such as a
      patient's desire for a second opinion, as affecting revascularization decisions.
      The results of that study are further examined here, using factor analysis to
      identify significant interrelationships among the non-clinical variables, which
      could contribute to disparities in coronary revascularization (i.e., percutaneous
      transluminal coronary angioplasty [PTCA] or coronary artery bypass graft [CABG]).
      Five content themes emerged using factor analysis; these are related to the
      patient's socioeconomic/lifestyle status, treatment preference, physician
      interaction, health-assertiveness, and aggressiveness. For the lifestyle theme,
      family physicians had higher mean scores (14.8) than internists, cardiologists,
      and cardiothoracic surgeons (13.7, 13.6, and 12.6, respectively; overall p=.001);
      women had higher mean scores than men (15.0 vs. 13.7; p=.009). This implies that
      family medicine and female physicians perceived variables pertaining to patients'
      socioeconomic status or lifestyle (e.g., financial barriers, unlikely to adopt
      healthy behaviors) as precluding some patients from being revascularized.
      Additionally, female, more than male, physicians (15.0 vs.13.6; p=.006) perceived
      health assertive patients (e.g., involved in treatment decisions, will quit
      smoking) as having easier access to the procedures. The results of the present
      analysis suggest that disparities in cardiac care arise from complex psychosocial
      interactions, which are influenced by characteristics of the physician as well as
      the patient.

PMID- 16960323
TI  - The health care experiences of rural Medicaid beneficiaries.
AB  - Medicaid plays a vital role in rural America, yet, because of data limitations,
      little research exists on the health care experiences of low-income rural adults.
      We use data from the National Survey of America's Families, with its oversample
      of low-income populations, to examine differences in access to and use of care
      between urban and rural Medicaid beneficiaries, and between Medicaid
      beneficiaries and low-income privately insured adults in urban and rural areas.
      We find evidence that access to care under Medicaid is worse than under private
      insurance in both urban and rural areas; however, Medicaid beneficiaries have a
      more consistent level of access across urban and rural areas than do low-income
      privately insured people.

PMID- 16960324
TI  - The coverage priorities of disabled adult Medi-Cal beneficiaries.
AB  - Medi-Cal, like other Medicaid programs around the U.S., has been pressed to cut
      its budget. We report the results of a project using the CHAT (Choosing
      Healthplans All Together) exercise, designed to ascertain the priorities of
      disabled adult Medi-Cal beneficiaries to inform any decisions regarding Medi-Cal
      benefits. Participants voiced greatest interest in maintaining a wide spectrum of
      benefits and access to a large pool of providers and were most willing to
      restrict pharmacy benefits. The resulting findings may be of value to legislators
      drafting Medicaid proposals that revise benefits for this vulnerable population.

PMID- 16960325
TI  - Emergency room use and access to primary care: evidence from Houston, Texas.
AB  - To cope with the rising number of uninsured, communities around the country are
      pursuing a variety of strategies to expand local health care safety nets. One
      measure that has been suggested to evaluate what is working is primary care
      related emergency department (ED) visits. In this paper, we evaluate the
      applicability of this measure as an access indicator by examining its correlation
      with other indicators of medical under-service. We obtained ED visit data from
      safety net hospitals in Houston, Texas and applied the New York University ED
      Algorithm to estimate the rate of visits that were primary care-related. We then
      examined at the ZIP code level the correlation of primary care-related ED visits
      per 1,000 population with the federal government's Index of Medical Underservice
      (IMU), the poverty rate, and the uninsurance rate. Primary care-related ED visits
      were found to be weakly correlated with the IMU and strongly correlated with the
      rate of uninsurance and poverty. These findings suggest that the combination of
      this indicator with other measures of access could be used to monitor and
      evaluate local initiatives designed to expand care and coverage to the medically
      underserved.

PMID- 16960326
TI  - Multiple perspectives on being uninsured and barriers to health coverage in a
      rural western state.
AB  - The purpose of this study was to describe the impact of being uninsured and
      barriers to obtaining health care coverage for people in a rural state. Focus
      groups and in-depth interviews were conducted with uninsured people, small
      business owners, health care providers, and key informants (such as state health
      officials, business leaders, and safety net providers). Uninsured people
      recognize the difficulties they face trying to obtain insurance and health care
      because of cost and ineligibility for public programs. Health care providers are
      frustrated in their care of the uninsured because of inability to obtain needed
      resources. Small business owners struggle with decisions about whether to provide
      health insurance or not, and find cost the greatest barrier. The impact of
      uninsurance on individuals, families, health care providers, and small business
      owners in a rural state is great, both economically and emotionally.
      Comprehensive approaches must be taken to increase access to health insurance and
      health care.

PMID- 16960327
TI  - Self-perceived loss of control and untreated dental decay in African American
      adults with and without sickle cell disease.
AB  - The aim of this cross-sectional study was to investigate the association between
      self-perceived loss of control as measured by dental external locus of control
      summary scores, with the amount of untreated dental decay in African American
      adults with sickle cell disease (SCD) and African Americans adults without SCD.
      The sample included 102 subjects with SCD and 103 subjects without SCD matched on
      age, sex, and recruitment location (mean age of all subjects 35.4 years, 55.6%
      female). Subjects with SCD in the highest quartile for dental external locus of
      control summary scores had 2.58-fold (CI 1.05, 6.34) as much untreated decay as
      those in the lowest quartile (p<.05) in multivariable analysis using the negative
      binomial regression model. For subjects without SCD, those in the highest
      quartile for dental external locus of control summary scores had 3.00-fold (CI
      1.38, 6.49) as much untreated decay as those in the lowest quartile (p<.05) using
      similar analysis. This study showed that higher dental external locus of control
      is associated with increased untreated tooth decay, both for African Americans
      with and without SCD and that the magnitude of the association did not differ
      across groups.

PMID- 16960328
TI  - The digital divide in public e-health: barriers to accessibility and privacy in
      state health department websites.
AB  - State health departments have placed a tremendous amount of information, data,
      and services online in recent years. With the significant increase in online
      resources at official health sites, though, have come questions concerning equity
      of access and the confidentiality of electronic medical materials. This paper
      reports on an examination of public health department websites maintained by the
      50 state governments. Using a content analysis of health department sites
      undertaken each year from 2000 to 2005, we investigate several dimensions of
      accessibility and privacy: readability levels, disability access, non-English
      accessibility, and the presence of privacy and security statements. We argue that
      although progress has been made at improving the accessibility and
      confidentiality of health department electronic resources, there remains much
      work to be done to ensure quality access for all Americans in the area of public
      e-health.

PMID- 16960330
TI  - Molecular cloning and characterization of a Pichia pastoris ortholog of the yeast
      Golgi GDP-mannose transporter gene.
AB  - There are two structural profiles in the yeast Golgi. The Golgi of Saccharomyces
      cerevisiae is composed of a number of vesicular compartments dispersed in the
      cytoplasm as recognized by a large number of Golgi marker proteins. In contrast,
      the Golgi of Pichia pastoris was reported to be organized in a small number of
      stacked cisternae located near the transitional endoplasmic reticulum (tER) sites
      by electron microscopy and immunofluorescent staining of a few marker proteins.
      The guanosine diphosphate (GDP)-mannose transporter (GMT) is an essential
      component in the yeast Golgi apparatus. We isolated an ortholog of the GMT gene
      of P. pastoris and visualized the gene product by epitope tagging to verify the
      structural characteristics of the Golgi. The tagged product in P. pastoris cell
      was observed in rod-like compartments in which Och1 mannosyltransferase was also
      found and the tER marker Sec12 and Sec13 proteins localized very close to them.
      The present results add further evidence of the restricted localization of the
      Golgi in P. pastoris cell.

PMID- 16960331
TI  - Phylogenetic analysis of gamma-proteobacteria inferred from nucleotide sequence
      comparisons of the house-keeping genes adk, aroE and gdh: comparisons with
      phylogeny inferred from 16S rRNA gene sequences.
AB  - Nucleotide sequence comparisons of three house-keeping genes, adenylate kinase
      (adk), shikimate dehydrogenase (aroE), and glucose-6-phosphate dehydrogenase
      (gdh), were used to infer the phylogeny of 33 gamma-proteobacteria. Phylogenetic
      trees inferred from each gene, and from the concatenated sequences of all three
      genes, are, in general, similar to a 16S rRNA gene-inferred tree. Similar
      grouping of bacteria are revealed at the family, genus, species and strain levels
      in all five trees. The house-keeping genes, however, show a higher rate of
      nucleotide sequence substitutions. Consequently, they can possibly probe deeper
      branches of a phylogenetic tree than the 16S rRNA gene. However, because their
      nucleotide sequences are not as highly conserved among gamma-proteobacteria,
      family- or genus-specific primers would need to be designed for the amplification
      of any of these three house-keeping genes. Since these genes are used in
      multilocus sequence typing, it is expected that the number of sequences publicly
      available for many taxa will increase over time proving them very useful either
      at complementing 16S rRNA-inferred phylogenies or for specific, targeted,
      phylogenetic analysis.

PMID- 16960332
TI  - Factors affecting the adsorption of bacteriocins ST194BZ and ST23LD to
      Lactobacillus sakei and Enterococcus sp.
AB  - Bacteriocins ST194BZ and ST23LD, produced by Lactobacillus plantarum, inhibit
      Gram-positive and Gram-negative bacteria. Images obtained by atomic force
      microscopy showed clear signs of membrane damage of Lactobacillus sakei,
      accompanied by the leakage of DNA and beta-galactosidase. Adsorption of the
      bacteriocins to cells was increased when cells were treated with buffers at pH
      values above neutral. An increase in bacteriocin ST194BZ adsorption to cells of
      Enterococcus sp. and L. sakei was observed with an increase in incubation
      temperatures, but at different rates for the two species. Treatment of the two
      species with various inorganic salts and solvents gave different results
      regarding the adsorption of the two bacteriocins. In general, pre-treatment of
      the two sensitive cells with Triton X-100, Triton X-114 and chloroform increased
      the adsorption of the two bacteriocins. Increased adsorption of bacteriocin
      ST23LD to L. sakei was recorded when the cells were pre-treated with Tris and NH4
      citrate. Treatment of Enterococcus sp. and L. sakei with Na-EDTA and SDS
      decreased the adsorption of the two bacteriocins. Variable results were recorded
      with inorganic salts.

PMID- 16960333
TI  - Extended spectrum beta-lactamase producing Enterobacteriaceae in Lebanese ICU
      patients: epidemiology and patterns of resistance.
AB  - Our study aims to investigate and describe the epidemiology of the intestinal
      carriage of ESBL-PS in intensive care units of five Lebanese hospitals and to
      analyze the potential risk factors for the acquisition of these strains. At the
      same time, we intend to determine the patterns of susceptibility of these
      strains, exploring therefore the availability of alternative treatment. One
      thousand, four hundred forty-two fecal samples were collected between January 1,
      2003 and March 31, 2003 from 378 patients admitted to the ICUs of five Lebanese
      tertiary care general hospitals located in different areas of Lebanon. ESBL
      production was detected by the double disk synergy test and antibiotic
      susceptibility of ESBL-producing strains as well as minimum inhibitory
      concentrations were determined. A paired case-control study was undertaken to
      identify risk factors for carriage of ESBL-PS. One hundred eighteen strains
      isolated from 72 subjects were identified as ESBL producers, including 95 (80.5%)
      E. coli, 16 (13.6%) Klebsiella pneumoniae, and 7 (5.6%) Enterobacter cloacae. A
      higher rate of multiple ESBL-PS carriage was described among these acquisition
      cases (21 double carriages and 3 triple carriages of ESBL-PS compared to only 1
      double carriage of ESBL-PS at admission). In general, similar trends of
      susceptibility were observed in the different hospitals. As expected, the lowest
      MIC was observed with imipenem for all E. coli, Klebsiella, and Enterobacter
      isolates. Ciprofloxacin, followed by trimethoprim-sulfamethoxazole seem to be
      associated with the lowest susceptibility. In vitro susceptibility to cefoxitin
      for all isolates was 74.6%; more resistance was associated to ceftazidime (90.7%)
      than to cefotaxime (69.7%). Our data agree with other national and international
      reports showing the increase in ESBL-PS carriage in ICU patients. They
      demonstrate the endemic character of this carriage in Lebanese hospitals and the
      important risk factors including immunosuppression and evidence of ESBL
      infection. The highly resistant profile of ESBL-PS to antimicrobial agents
      available for treatment reflects the severity of this issue. The significance of
      this study resides in the direct correlation between our results and the
      nationwide increase in multi-drug resistant bacteria and the continuous change in
      bacterial resistance epidemiology. Our data may have an important impact on
      infection control policies in hospitals and on treatment of infectious diseases.

PMID- 16960334
TI  - Bioaccumulation and biosorption of chromium by Aspergillus niger MTCC 2594.
AB  - Chromium toxicity is of prime concern due to chrome tanning processes in the
      leather sector. Chrome tanning results in the discharge of toxic levels of
      chromium causing pollution hazards. Chromium levels of Cr(III) and Cr(VI) were
      high above permissible limits in chrome samples after chrome tanning. The
      potential of Aspergillus niger MTCC 2594 to accumulate chromium as well as its
      biosorption capacity is investigated in this study. Bioaccumulation of Cr(III)
      and Cr(VI) in the spent chrome liquor has resulted in a 75-78% reduction of the
      initial Cr content in 24-36 h. A. niger biomass is found to be very effective in
      the biosorption of Cr(III) and Cr(VI) in spent chrome liquor. Maximum adsorption
      of 83% for biosorption of Cr(III) at 48 h and 79% of Cr(VI) at 36 h in spent
      chrome liquor is observed. The biosorption characteristics fit well with Langmuir
      and Freundlich isotherms and the adsorption parameters are evaluated. The
      biosorption of Cr also follows Lagergren kinetics. A. niger biomass is
      effectively used for the biosorption of chromium with 79-83% Cr removal in 36-48
      h.

PMID- 16960335
TI  - Intrageneric structure of the genus Gluconobacter analyzed by the 16S rRNA gene
      and 16S-23S rRNA gene internal transcribed spacer sequences.
AB  - Forty-nine strains belonging to the genus Gluconobacter were re-examined with
      respect to their species identification based on the sequences of the 16S rDNA
      and 16S-23S rDNA internal transcribed spacer regions (ITS). A phylogenetic tree
      constructed from the 16S rDNA sequences indicated the presence of five clusters
      corresponding, respectively, to the major five species of the genus
      Gluconobacter, namely G. albidus, G. cerinus, G. frateurii, G. oxydans (type
      species), and G. thailandicus. The type strain of G. asaii, NBRC 3276T (T=type
      strain) was included in the G. cerinus cluster, which is consistent with the
      report that G. asaii is a junior subjective synonym of G. cerinus. Existence of
      the G. albidus, G. cerinus, G. frateurii, G. oxydans, and G. thailandicus
      clusters was also recognized by the ITS sequence analysis. Both sequence analyses
      revealed that the G. cerinus and G. frateurii clusters were heterogeneous. The G.
      cerinus cluster comprised three strains of G. cerinus and one strain of G.
      frateurii, while the G. frateurii cluster included ten strains of G. frateurii,
      three of G. cerinus, and eleven of G. oxydans. These results suggest that
      phenotypic differences among Gluconobacter species are ambiguous and the species
      definition must be re-evaluated. The 16S rDNA and ITS sequences determined in
      this study are valuable for the identification and phylogenetic analysis of
      Gluconobacter species.

PMID- 16960336
TI  - Flow cytometric analysis of phosphorylated histone H2AX following exposure to
      ionizing radiation in human microvascular endothelial cells.
AB  - We applied a flow cytometric method to quantify IR-induced histone H2AX
      phosphorylation at serine 139 (gammaH2AX) and compared those values to those
      obtained using a standard microscopy based foci counting method. After PFA
      fixation, methanol permeabilization was suitable for both FITC- or Alexa647
      gammaH2AX. In contrast, Alexa647-gammaH2AX was not suitable for ethanol
      permeabilization. Antibody concentrations at 1-2 microg/ml yielded the highest
      gammaH2AX positive percentage for both antibodies. Without DAPI staining,
      gammaH2AX formation can be measured as a relative fold increase. Values
      determined by bivariant flow cytometric analysis and those obtained using
      microscopic foci formation exhibited a good quantitative correlation. Values
      obtained by both methods could vary according to the gating or threshold setting
      used. gammaH2AX positive cells increased as a function of radiation dose (2-16
      Gy) followed by a dose-dependent decay. The free radical scavenger N-acetyl-L
      cysteine (NAC), if administered at a concentration of 4 mM 30 min before IR, was
      effective in reducing IR-induced gammaH2AX formation in all phases of the cell
      cycle. We have developed a simplified and quantitative flow cytometry based
      method to measure IR-induced gammaH2AX in cells and demonstrated strong
      correlation to values obtained by a standard automated digital microscopic foci
      analysis along with NIH ImageJ custom macro software.

PMID- 16960337
TI  - A new system for detecting mutations in arabidopsis thaliana and the mutational
      spectra resulting from ethylmethanesulfonate treatment.
AB  - A system was developed for the detection and analysis of mutations occurring on
      chromosomal DNA in plants. The plasmid pML4, carrying the Escherichia coli rpsL
      gene, a target gene for mutagenesis, was inserted into a shuttle vector,
      pCGN5138, to construct a plasmid which could be used for the transformation of
      plants. pML4 sequences were introduced into Arabidopsis thaliana mediated by
      Agrobacterium. The pML4 DNA was rescued from transgenic Arabidopsis plants
      exposed to mutagens, and the plasmids were introduced into Escherichia coli DH10B
      to isolate mutant clones. In this system, any form of inactivation mutation in
      the rpsL gene can be positively selected since it makes the E. coli cells
      resistant to streptomycin. Here we report that the system could detect the
      mutagenic effect of ethylmethanesulfonate (EMS). Further characterization of the
      mutants revealed that G:C to A:T transitions predominated among the EMS-induced
      mutations. This assay system is useful for the detection and analysis of
      mutations arising on chromosomal DNA in plants, and should be useful for
      evaluating analysis of the effects of environmental mutagens.

PMID- 16960338
TI  - Distinct modes of cell death by ionizing radiation observed in two lines of
      feline T-lymphocytes.
AB  - We have examined in vitro radiosensitivities and radioresponses to (60)Co gamma
      rays irradiation in feline T-lymphocyte cell lines, FeT-J and FL-4. There seemed
      to be no significant difference in clonogenic survival between the two lines. The
      mean lethal dose for both was both 1.9 Gy, and surviving fraction at 2 Gy was
      0.30 and 0.48 for FeT-J and FL-4 cells, respectively. However, TUNEL assay
      indicated much higher degrees of apoptosis induction in FeT-J cells (>40%) than
      in FL-4 cells (<10%) at 4 days after 15 Gy irradiation. Microscopic examination
      revealed a larger population of multi-nucleate cells in FL-4 cells (60.3%) than
      in FeT-J cells (16.0%) at 4 days after 15 Gy irradiation, suggesting that a
      larger ratio of mitotic catastrophe occurred in FL-4 cells. These results suggest
      that FeT-J is more likely to be induced into apoptosis and FL-4 is more likely to
      fall into mitotic catastrophe, and eventually necrosis; both of them showed a
      similar surviving fraction against gamma-rays. The results also indicate that FL
      4 cells follow a process other than apoptosis to cell death, suggesting the
      presence of a regulatory mechanism that may control the relationship between
      mitotic catastrophe and apoptosis in feline T-lymphocytes.

PMID- 16960339
TI  - GATA transcription factors and hematological diseases.
AB  - The development of mature blood cells from hematopoietic stem cells is regulated
      by transcription factors that control and coordinate the expression of lineage
      specific genes. The GATA family consists of six transcription factors that
      function in hematopoietic and endodermal development. Among them, GATA-1 is
      expressed in erythroid, megakaryocytic, eosinophil and mast cell lineages, and
      GATA-2 is expressed in stem and progenitor cells, at more immature stage compared
      with GATA-1. Based on the characteristic phenotypes of GATA-1 and GATA-2 mutant
      mice, it has been suggested that mutations of these GATA genes in humans may
      result in the onset of certain clinical diseases. To date, mutations of GATA-1
      gene have been found in inherited anemia and thrombocytopenia, and Down syndrome
      related acute leukemia, which exhibits megakaryocytic phenotypes and frequently
      occurs in patients with Down syndrome. In contrast, no mutation of GATA-2 gene
      has been identified in hematological diseases; however, we found the expression
      level of GATA-2 is significantly decreased in CD34 positive cells in patients
      with aplastic anemia. Since GATA-2 functions in the proliferation of
      hematopoietic stem cells, the reduction of GATA-2 expression in CD34 positive
      cells may result in the decreased number of hematopoietic stem cells, which is
      the characteristic feature of aplastic anemia. Based on these lines of evidence,
      some types of hematological diseases may be defined as transcription factor
      diseases.

PMID- 16960340
TI  - Determinants of self-rated health among community-dwelling women aged 40 years
      and over in Japan.
AB  - In developed countries, the elderly population is growing rapidly. Self-rated
      health is an important indicator of health and has been the focus of a number of
      aging studies. However, little is known about the possible differences in
      determinants of self-rated health according to age. Self-rated health and its
      possible determinants were examined in 542 community-dwelling Japanese women aged
      40 to 91 years. The proportion of women with poor self-rated health increased
      with age. Approximately half of the women had poor self-rated health among women
      aged 80 years and over. We used multiple logistic regression analysis to examine
      the association with poor self-rated health in women aged 40 to 64 years (n =
      248) and 65 years and over (n = 294). Lower physical activity and a greater
      number of comorbidities were associated with poor self-rated health for ages 40
      to 64 and 65 years and over. Furthermore, the risk of poor self-rated health
      increased by 1.5-fold with every increase in the number of painful joints in the
      lower extremities for the 40- to 64-year-old age group, and increased by 2-fold
      with back pain for those 65 years and over. The determinants of self-rated health
      were similar in both middle-aged and elderly Japanese women. Our results could
      contribute to effective interventions to improve quality of life among Japanese
      women.

PMID- 16960341
TI  - An off-seasonal amantadine-resistant H3N2 influenza outbreak in Japan.
AB  - An off-season community influenza outbreak with high prevalence of amantadine
      resistant influenza A/H3N2 occurred during September-October 2005 in Nagasaki
      Prefecture, Japan, prior to standard influenza circulation. A total of 48
      patients with influenza-like-illness (ILI) visited a clinic during the outbreak
      and 27 (69.2%) of 39 ILI patients were positive for influenza A with rapid
      antigen testing (Quick Vue Rapid SP Influ). Nine patients were not tested because
      their symptoms were compatible for influenza without examination. Nasopharyngeal
      swabs were obtained from 4 of 27 rapid test positive patients, and influenza H3N2
      strain was isolated from one out of four. The 4 nasopharyngeal samples were
      positive for influenza A M2 gene in polymerase chain reaction, and sequencing
      results all showed identical mutation at position 31, serine to asparagine (S31N)
      in the gene, conferring amantadine resistance. The phylogenetic tree analysis
      demonstrated that the hemagglutinin (HA) gene sequences of the 4 samples formed a
      distinct cluster (named clade N) from recent circulating H3N2 strains,
      characterized by dual mutations at position 193, serine to phenylalanine (S193F),
      and at position 225, asparatic acid to asparagine (D225N). Our findings suggested
      that an off-season community influenza outbreak in Nagasaki was caused by a
      distinct clade in H3N2 (named clade N), which possessed characteristics of
      amantadine resistance.

PMID- 16960342
TI  - Sustained clinical improvement of a patient with decompensated hepatitis B virus
      related cirrhosis after treatment with lamivudine monotherapy.
AB  - Hepatitis B virus (HBV) infection, which causes liver cirrhosis and
      hepatocellular carcinoma, remains a major health problem in Asian countries.
      Recent development of vaccine for prevention is reported to be successful in
      reducing the size of chronically infected carriers, although the standard medical
      therapies have not been established up to now. In this report, we encountered a
      patient with decompensated HBV-related cirrhosis who exhibited the dramatic
      improvements after antiviral therapy. The patient was a 50-year-old woman.
      Previous conventional medical treatments were not effective for this patient,
      thus this patient had been referred to our hospital. However, the administration
      of lamivudine, a reverse transcriptase inhibitor, for 23 months dramatically
      improved her liver severity. During this period, no drug resistant mutant HBV
      emerged, and the serum HBV-DNA level was continuously suppressed. These
      virological responses were also maintained even after the antiviral therapy was
      discontinued. Moreover, both hepatitis B surface antigen and e antigen were
      observed to have disappeared in this patient. The administration of lamivudine to
      patients with HBV-related cirrhosis, like our present case, should be considered
      as an initial medical therapeutic option, especially in countries where liver
      transplantation is not reliably available.

PMID- 16960343
TI  - The status of Internet access in adult patients with atopic dermatitis in Japan.
AB  - The Internet has provided open access to health- and disease-related information
      for people with chronic diseases. Atopic dermatitis (AD) is mostly chronic, and
      the treatment of AD often requests some self-management such as skin care. For
      this situation, adult AD patients may have a motive of obtaining information on
      AD from various sources such as the Internet. Although the status of Internet
      access among AD patients has not been thoroughly investigated, knowledge about
      this status may be useful to understand AD patients in primary care. We studied
      the actual status among 62 adult Japanese outpatients with AD (male:female =
      29:33; mean age [+/- S.D.]: 27.8 +/- 7.9 years). All 62 patients owned cellular
      phones, while 51 subjects (82.3%) owned personal computers (PCs). Internet web
      site information on both general health and AD was more commonly accessed via PCs
      rather than cellular phones, but the access rates via PCs were only 35.3% among
      all users of PCs. When AD patients assessed the extent of credibility of web site
      information on AD on a scale of 0 to 100 points, it was at best 52.4 +/- 19.8
      points. Moreover, both the duration and severity of AD had a positive influence
      on the credibility of information on AD. These results suggest that Internet
      access is not common and the information is not necessarily credible among adult
      AD patients in Japan, and that more consideration is needed for the Internet to
      become a powerful and vital source to support health care for AD.

PMID- 16960344
TI  - Cervical plexus block helps in diagnosis of orofacial pain originating from
      cervical structures.
AB  - Headache associated with cervical lesions is called cervicogenic headache and
      involves the occiput but not the orofacial region. However, patients occasionally
      present with orofacial pain accompanied by neck symptoms. This study investigates
      whether orofacial pain can originate from the neck and whether cervical plexus
      block can help in diagnosis. We enrolled eight patients suffering from chronic
      orofacial pain that had not been relieved by dental treatment. Radiographic and
      magnetic resonance imaging revealed abnormal findings in the neck in seven of
      them. To identify the origin of the orofacial pain, we firstly blocked peripheral
      sensory input from the oral cavity and surrounding tissues, followed by that from
      deep cervical structures. We injected local anesthetics around the painful
      orofacial region, then to the tender points in the masticatory and superficial
      cervical muscles (trigger point injection), and consequently around the cervical
      plexus. Pain was assessed using a pain relief score compared with pre-treatment
      control values. Local anesthesia in the painful oral region provided insufficient
      relief whereas trigger point injection significantly relieved pain. The amount of
      pain relief generated by the deep cervical plexus block was more significant than
      that produced by any other procedures. We conclude that certain types of
      orofacial pain originate from cervical structures and that a deep cervical plexus
      block can be helpful in differentially diagnosing such pain.

PMID- 16960346
TI  - Metabolic syndrome as a predictor of non-dipping hypertension.
AB  - Metabolic syndrome (MS) and non-dipping hypertension both increase cardiovascular
      mortality. Although both clinical modalities share common pathophysiologic
      factors in their etiologies, previous studies did not find any association
      between them. We aimed to investigate the association between MS and non-dipping
      blood pressure by comparing different definitions of MS. One-hundred-thirty-two
      consecutive patients (58 men) who underwent 24-hour ambulatory blood pressure
      monitoring were analyzed. MS was evaluated according to the currently used Adult
      Treatment Panel (ATP) III definition criteria, named MS-ATP III. In order to
      reveal the weights of risk contributing to MS, a new diagnostic scoring method
      (MS-Score) was used in comparison with MS-ATP III. Nocturnal non-dipping refers
      to a reduction in average systolic and/or diastolic blood pressure at night (< or
      = 10%) compared with daytime average values. Non-dipping pattern was found in
      61.4% of patients. The frequency of MS according to MS-Score, but not MS ATP III,
      was significantly higher in patients with non-dipping pattern than those without
      it (p = 0.009). Although more prominent in the nighttime, MS-Score showed
      positive correlation with all systolic blood pressure results (r = 0.27, p =
      0.002). Adjusted for baseline characteristics, high (> or = 27.5) MS-Score
      remained as an independent predictor of non-dipping pattern (OR 2.64, p = 0.038).
      Finally, high MS-Score, but not MS-ATP III, is a predictor of non-dipping
      pattern. Nighttime systolic blood pressure is higher in patients with high MS
      Score. Therefore, patients with high MS-Score may be more prone to cardiovascular
      events than those with low MS-Score.

PMID- 16960345
TI  - Identification of a morphometrical parameter that predicts the response to
      splenectomy in patients with idiopathic thrombocytopenic purpura.
AB  - Idiopathic thrombocytopenic purpura (ITP) is an isolated thrombocyte disease that
      has no correlation with other causes of clinical thrombocytopenia in adults.
      About 70% of patients with ITP were successfully treated by medical care and
      splenectomy, but nearly 30% of ITP patients do not respond to these treatments.
      The aim of this study is to evaluate the predictive factors that affect the
      success of treatment in 26 patients with ITP. Thirteen patients with ITP
      responded to splenectomy (responsive group), whereas 13 other patients were
      resistant to medical treatment and splenectomy (resistant group). The control
      group consisted of 13 patients who had undergone posttraumatic splenectomy. Age,
      sex, spleen weight, the number of follicles per mm(2), and the length of time
      between diagnosis and splenectomy were retrospectively analyzed. No significant
      difference was found between the groups with respect to these variables. Mean
      maximum follicle diameter (MMaFD), mean minimum follicle diameter (MMiFD), and
      the number and distribution of CD56 (+) cells were evaluated for each spleen
      specimen. There was no statistical difference in the distribution of CD56 (+)
      cells between the ITP patients and the control group, but the number of CD56 (+)
      cells was significantly higher in the control group than in patients with ITP.
      While MMiFD showed no statistical difference between the groups of ITP patients,
      a MMaFD of 350 microm and above was significantly more likely in the resistant
      group than in the other groups. In conclusion, this study has shown that the
      MMaFD is a significant predictor of the response to splenectomy.

PMID- 16960347
TI  - Rapid detection of lamivudine-resistant hepatitis B virus mutations by PCR-based
      methods.
AB  - Hepatitis B virus (HBV) is one of the major causes of liver disease worldwide,
      and chronic HBV infection may progress to cirrhosis and hepatocellular carcinoma.
      Mutations at the active site of DNA polymerase of HBV, tyrosine-methionine
      aspartate-aspartate (YMDD) motif, render infected patients resistant to antiviral
      drug (Lamivudine) therapy. Hence, sensitive and specific methods aimed at
      detecting the mutants are essential. The purpose of this study was to develop
      methods for detecting the mutations at YMDD by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) and real-time PCR using
      locked nucleic acid (LNA)-mediated TaqMan probes. The results obtained by these
      methods were compared with those examined by conventional direct sequencing on
      serum samples of 77 patients treated with lamivudine. Our results show that both
      PCR-RFLP and real-time PCR could detect wild type, YMDD, and its mutants,
      tyrosine-isoleucine-aspartate-aspartate and tyrosine-valine-aspartate-aspartate.
      In addition, the mixtures of the wild-type virus and its mutants in the serum
      sample were detected. Importantly, real-time PCR is less time-consuming, and more
      sensitive for the detection of mixed populations than PCR-RFLP. The real-time PCR
      with LNA-mediated TaqMan probes is a sensitive, specific and rapid detection
      method for mutations at the YMDD motif, which will be essential for monitoring
      patients undergoing lamivudine antiviral therapy.

PMID- 16960348
TI  - Unusual presentation of tuberculosis as a splenic mass.
AB  - Tuberculosis is an important health problem in developing countries, with varying
      clinical presentations depending on the organs/systems involved. Tuberculosis is
      mostly seen in immuno-compromised individuals, such as those with acquired immune
      deficiency syndrome or malignancies. Here we report a case of a spleen
      tuberculoma in a 29-year-old male patient with no known immune deficiency. He
      first presented with abdominal pain, and subsequent ultrasonographic examination
      revealed a splenic lesion of 10 cm in diameter. A computerized tomography scan of
      the abdomen confirmed the presence of a solitary, hypodense, septated cystic
      lesion. Lack of evidence supporting the presence of a splenic infection or a
      primary/metastatic malignancy prompted explorative surgery where a septated
      abscess formation was discovered and splenectomy was performed. Histopathological
      examination revealed granulomatous inflammatory changes with Langerhans-type
      giant cells, which are consistent with tuberculosis. For a period of two months,
      antituberculosis therapy with four drugs, isoniazid, rifampicin, pyrazinamide,
      and ethambutol, was carried out. Pyrazinamide and ethambutol were quitted at the
      end of two months. Therapy with isoniazid and rifampicin was planned for an
      additional 10 months. We would like to call attention to yet another atypical
      presentation of extrapulmonary tuberculosis.

PMID- 16960349
TI  - Chronic subdural hematoma coexisting with ligamentum flavum hematoma in the
      lumbar spine: a case report.
AB  - We present a case of a chronic spinal subdural hematoma combined with a
      ligamentum flavum hematoma in the lumbar spine treated surgically. An 83-year-old
      woman receiving antiplatelet medicine due to an angina suffered from pain in her
      lower extremity and gait disturbance after a backward fall. Radiological findings
      including magnetic resonance imaging (MRI) revealed hematoma in the ligamentum
      flavum at the level of L2 - L3 and a chronic subdural hematoma at the level from
      L3 to L5. Laminectomy through L2 to L5 was performed and a hematoma existing in
      the ligamentum flavum and cystic mass was removed. A chronic subdural hematoma
      was spontaneously evacuated after splitting of the dura mater and an intact
      arachnoid membrane was observed with no leakage of cerebrospinal fluid. Her
      clinical symptoms completely disappeared after surgery. To the best of our
      knowledge, this is the first case of combination of chronic subdural hematoma and
      ligamentum flavum hematoma in the lumbar spine treated by surgery. Chronic spinal
      subdural hematoma and hematoma in the ligamentum flavum should be considered as a
      cause of progressive nerve root compression in patients with anticoagulant
      therapy, and an appropriate pre-operative diagnosis would be needed to achieve
      complete decompression of subdural and epidural hematoma.

PMID- 16960350
TI  - Posttranscriptional regulation by the upstream open reading frame of the
      phosphoethanolamine N-methyltransferase gene.
AB  - Phosphoethanolamine N-methyltransferase (PEAMT) is involved in choline
      biosynthesis in plants. The 5' untranslated region (UTR) of several PEAMT genes
      was found to contain an upstream open reading frame (uORF). We generated
      transgenic Arabidopsis calli that expressed a chimeric gene constructed by fusing
      the 5' UTR of the Arabidopsis PEAMT gene (AtNMT1) upstream of the beta
      glucuronidase gene. The AtNMT1 uORF was found to be involved in declining levels
      of the chimeric gene mRNA and repression of downstream beta-glucuronidase gene
      translation in the calli when the cells were treated with choline. Further, we
      discuss the role of the uORF.

PMID- 16960351
TI  - Linear 3-hydroxybutyrate tetramer (HB4) produced by Sphingomonas sp. is
      characterized as a growth promoting factor for some rhizomicrofloral composers.
AB  - Sphingomonas spp. of alpha-proteobacteria often play a role in assisting the
      development of microfloral communities under adverse soil conditions. Using a
      Frateuria sp. as an indicator for bacterial growth assay, we investigated the
      bacterial growth-promoting factor in the culture fluids of Sphingomonas sp. EC
      K085. This factor was successfully isolated and identified as linear (R,R,R,R)-3
      hydroxybutyrate tetramer (HB4), having a hydroxy-end and a carboxy-end group.
      When 28 mug of HB4 was charged on a paper disc, impregnated Frateuria sp. cells
      in modified Winogradsky agar medium exhibited a promoted cell growth to form a
      clear colony emerging zone after a 2-day incubation.

PMID- 16960352
TI  - Nucleotide sequences and organization of the genes for carotovoricin (Ctv) from
      Erwinia carotovora indicate that Ctv evolved from the same ancestor as Salmonella
      typhi prophage.
AB  - Carotovoricin Er (CtvEr), which is produced by a plant soft rot disease causative
      agent, Erwinia carotovora subsp. carotovora Er, is a high-molecular-weight
      bacteriocin showing Myoviridae phage-tail-like morphology with contractile sheath
      and plural tail fibers. We determined the complete nucleotide sequences of CtvEr
      genes on the E. carotovora Er chromosome and report that CtvEr genes consist of
      lysis cassette, major and minor structural protein gene clusters. Four promoters
      were identified. The lysis gene cassette, which is composed of the genes for
      lysis enzyme and holin, was also identified and characterized. The nucleotide
      sequences and organization of the genes for CtvCGE, which is produced by E.
      carotovora strain CGE234-M403 with the morphology similar to CtvEr, were also
      determined and compared to that of CtvEr, and it was found that CtvCGE is almost
      identical to CtvEr except for tail fibers which are involved in the killing
      spectra of both bacteriocins. We also explain that the gene organization and the
      deduced amino acid sequences of both carotovoricins are very close to those of
      prophage, which is lysogenized in the chromosome on Salmonella enterica serovar
      Typhi CT18. These findings strongly suggest that Ctv evolved as a phage tail-like
      bacteriocin from a common ancestor with Salmonella typhi prophage.

PMID- 16960353
TI  - Extensive RNA editing in transcripts from the PsbB operon and RpoA gene of
      plastids from the enigmatic moss Takakia lepidozioides.
AB  - RNA editing is a post-transcriptional process that changes individual nucleotides
      in transcripts, and usually occurs in the plastids of land plants. The number of
      RNA editing sites in a plastid is significantly divergent in bryophytes, ranging
      from zero in liverworts to almost 1,000 sites in hornworts. In this study, we
      identified 132 RNA editing sites in the transcripts of six genes from the psbB
      operon and the rpoA of the moss Takakia lepidozioides. This is the highest number
      of RNA editing sites known in this region among land plant species. All were
      cytidine-to-uridine conversions. More than 91% of RNA editing occurred at the
      first or second codon positions, and it altered amino acid identity. Six editing
      sites created new translation initiation codons or stop codons. Thirty-two sites
      were commonly observed in the hornwort Anthoceros angustus. This finding suggests
      that the enigmatic bryophyte Takakia is closely related to hornworts with respect
      to RNA editing events.

PMID- 16960354
TI  - Regulation and functional relevance of milk fat globules and their components in
      the mammary gland.
AB  - Mammary gland and epithelial cells are unique to mammals and are under the
      control of lactogenic hormones such as prolactin. Recent findings indicated that
      major components of milk fat globule membrane (MFGM) are under the control of
      lactogenic hormones, and that the major components butyrophilin and xanthine
      oxidoreductase are indispensable for milk fat secretion. Further, prolactin
      signaling is negatively controlled by two highly related protein tyrosine
      phosphatases, PTP1B and TC-PTP. Milk fat globule EGF factor 8 (MFG-E8) is one of
      the major components of MFGM and is upregulated during lactation. MFG-E8 is
      further upregulated in the involuting mammary gland. MFG-E8 on exosome-like
      membrane vesicles in the milk recovered from post-weaning but not lactating
      mammary glands exhibits higher binding activity to phosphatidylserine and
      apoptotic mammary epithelial cells, and serves as a link between apoptotic
      mammary epithelial cells and phagocytes. Recent reports using MFG-E8 deficient
      mice support the view that MFG-E8 is indispensable for eliminating apoptotic
      mammary epithelial cells during involution.

PMID- 16960355
TI  - Distribution and metabolism of dihomo-gamma-linolenic acid (DGLA, 20:3n-6) by
      oral supplementation in rats.
AB  - We compared the dietary effects of dihomo-gamma-linolenic acid (DGLA) contained
      in the DGLA oil produced by a fungus with gamma-linolenic acid (GLA) on the fatty
      acid composition. Wistar rats were fed with three kinds of oil for two weeks as
      follows: (i) control group: corn oil; (ii) GLA group: borage oil; (iii) DGLA
      group: DGLA oil/safflower oil = 55:45. The DGLA concentrations in the liver,
      serum, and brain of the DGLA group were higher than those of the GLA oil group.
      We also examined the dose effect of DGLA. The DGLA levels in the liver, serum,
      and brain significantly increased with increasing dosage of DGLA in the diet.
      DGLA administration significantly increased the ratio of PGE1/PGE2 in the rat
      plasma. The mechanism for GLA administration to improve atopic eczema is thought
      to involve an increase in the concentration of DGLA metabolized from GLA, so
      these results suggest that the dietary effect of DGLA would be more dominant than
      GLA.

PMID- 16960356
TI  - Molecular characteristics of bovine serum albumin-dextran conjugates.
AB  - Bovine serum albumin (BSA)-dextran conjugates were prepared by using the Maillard
      reaction; depending on the ratio of dextran to BSA used, about 0.5-1 mol of
      dextran could be bound to 1 mol of native BSA. SDS-PAGE patterns revealed that
      BSA and dextran had been covalently bonded. Structural analyses by fluorescence
      spectroscopy and circular dichroism indicated that the BSA surface in each
      conjugate was covered with dextran without any great disruption of the native
      conformation. The conjugates could be grouped into two fractions on the basis of
      the weight-average molecular mass measured: the main fraction at 1.95-2.35 x
      10(5) g/mol and a less-abundant fraction with aggregates greater than 1.50 x
      10(6) g/mol. High-performance size-exclusion chromatography in conjunction with
      multi-angle laser light scattering detection revealed that the BSA-dextran
      conjugates prepared by using the Maillard reaction had various molar masses and
      radii.

PMID- 16960357
TI  - Effects of lactose on colon microbial community structure and function in a four
      stage semi-continuous culture system.
AB  - A semi-continuous four-channel colon simulator was used to study the effects of
      lactose for the first time on the growth and fermentation dynamics of colonic
      microbiota. In six separate simulations, lactose supplementation increased the
      total SCFA concentration by 3-5 fold as compared with the baseline in the
      respective vessels. The total bacterial density was inversely correlated with
      lactic acid production (P = 0.003), while production of butyrate (P = 0.007) and
      propionate (P = 0.02) correlated with higher numbers of bacteria. A major shift
      in the microbial community structure in the lactose supplemented vessels was
      demonstrated by bacterial genomic %G+C-profiling of the total population, where
      lactose supplementation induced a clearly dominant peak in the bifidobacteria
      prominent area, %G+C 60-65. The transient shift to increased numbers of
      bifidobacteria (23-27%) of all bacteria in the first two vessels was also
      confirmed by the bifidobacteria-specific QPCR-method. In conclusion, lactose
      produced dramatic changes in microbiota composition and activity as compared with
      the baseline fermentation.

PMID- 16960358
TI  - The CarA/LitR-family transcriptional regulator: Its possible role as a
      photosensor and wide distribution in non-phototrophic bacteria.
AB  - LitR is a MerR-family regulator that controls light-induced carotenogenesis in
      Streptomyces coelicolor. The introduction of litR conferred photo-dependent
      transcription activities on Streptomyces griseus, which does not perform photo
      responsive carotenogenesis. LitR discovers homologs encoded at illumination
      related loci of various non-phototrophic bacterial genomes. Probably, LitR acts
      not only as a transcriptional regulator but also a photosensor.

PMID- 16960359
TI  - Molecular cloning of streptomyces genes encoding vanillate demethylase.
AB  - The vanillate demethylase genes from Streptomyces sp. NL15-2K were cloned and
      sequenced. The vanA and vanB gene homologs, which encode the terminal oxygenase
      subunit (VanA) and the ferredoxin-type reductase subunit (VanB) of the enzyme
      respectively, were found in the sequenced 7.5-kb DNA region. Expression of the
      vanAB genes in Streptomyces lividans 1326 resulted in in vivo demethylation of
      veratric acid to vanillic acid.

PMID- 16960360
TI  - Cytoplasmic localization of the single glutamine synthetase in a unicellular red
      alga, Cyanidioschyzon merolae 10D.
AB  - Glutamine synthetase (GS) is a key enzyme for nitrogen assimilation. Although GS
      contains multiple molecular species found in plastid, mitochondria and cytoplasm
      in green plants and algae, genome analysis of a red alga, Cyanidioschyzon
      merolae, revealed a single nuclear gene for GS (CmGS). In this study, we
      experimentally determined the CmGS localization in the cytoplasmic compartment.

PMID- 16960361
TI  - Quantification of cyanamide contents in herbaceous plants.
AB  - Cyanamide (NH2CN) is found in nature, although it has long been recognized as an
      industrial product. Distribution of cyanamide in the plant kingdom was
      investigated using a direct quantitative determination method to detect and
      measure cyanamide by stable isotope dilution gas chromatography-mass spectrometry
      (the SID-GC-MS method). The SID-GC-MS method proved to be a robust way to
      quantify cyanamide contents in the extracts of 101 species of herbaceous plants.
      The average recovery of cyanamide from all plants tested was 55.6+/-20.3%. Vicia
      villosa and V. cracca contained cyanamide at 369-498 microg/gFW and 3,460-3,579
      microg/gFW respectively, while the other 99 species contained no detectable
      cyanamide (<1 microg/gFW). This result suggests that distribution of cyanamide in
      the plant kingdom is limited and uneven.

PMID- 16960362
TI  - 1,2-Dehydrolactarolide A, a new plant growth regulatory lactarane sesquiterpene
      from Lactarius vellereus.
AB  - A new lactarane sesquiterpene, 1,2-dehydrolactarolide A (1), together with
      lactarorufin A (2), 3-O-ethyllactarolide A (3) and 3-O-ethyllactarolide B (4),
      was isolated from a mushroom of the Russulaceae family, Lactarius vellereus.
      Additionally, two lactarane sesquiterpenes, lactarorufin A (2) and lactarolide A
      (5) were isolated from L. subpiperatus. 1,2-Dehydrolactarolide A (1) showed
      promotional activity (152% at 3.6 x 10(1) microM) toward radicle elongation in
      lettuce seedlings.

PMID- 16960363
TI  - Immobilization of UDP-galactose 4-epimerase from Escherichia coli on the yeast
      cell surface.
AB  - UDP-galactose 4-epimerase (EC 5.1.3.2, Gal E) from Escherichia coli catalyzes the
      reversible reaction between UDP-galactose and UDP-glucose. In this study, the Gal
      E gene from E. coli, coding UDP-galactose 4-epimerase, was cloned into pYD1
      plasmid and then transformed into Saccharomyces cerevisiae EBY100 for expression
      of Gal E on the cell surface. Enzyme activity analyses with EBY100 cells showed
      that the enzyme displayed on the yeast cell surface was very active in the
      conversion between UDP-Glc and UDP-Gal. It took about 3 min to reach equilibrium
      from UDP-galactose to UDP-glucose.

PMID- 16960364
TI  - Hydroxylation of oleanolic acid to queretaroic acid by cytochrome P450 from
      Nonomuraea recticatena.
AB  - A gene for cytochrome P450 (moxA) from Nonomuraea recticatena, coexpressed with
      camAB for pseudomonad redox partners in Escherichia coli, hydroxylated oleanolic
      acid to produce queretaroic acid. When we used the P450-induced whole-cell as a
      catalyst, only a small amount of queretaroic acid was produced, probably due to
      poor permeability of oleanolic acid into the E. coli cell. In an alternative
      approach with the cell-free reaction system, the conversion ratio increased up to
      17%.

PMID- 16960365
TI  - Enzymatic synthesis of L-pipecolic acid by Delta1-piperideine-2-carboxylate
      reductase from Pseudomonas putida.
AB  - L-Pipecolic acid is a chiral pharmaceutical intermediate. An enzymatic system for
      the synthesis of L-pipecolic acid from L-lysine by commercial L-lysine alpha
      oxidase from Trichoderma viride and an extract of recombinant Escherichia coli
      cells coexpressing Delta1-piperideine-2-carboxylate reductase from Pseudomonas
      putida and glucose dehydrogenase from Bacillus subtilis is described. A
      laboratory-scale process provided 27 g/l of L-pipecolic acid in 99.7% e.e.

PMID- 16960366
TI  - Vasodilating effect of di-peptides in thoracic aortas from spontaneously
      hypertensive rats.
AB  - In this study, we found that antihypertensive di-peptide Val-Tyr (VY) showed a
      vascular relaxation effect in KCl-induced contraction of thoracic aorta rings
      from 18-week-old spontaneously hypertensive rats among di-peptides of VY, Ile
      Tyr, and Tyr-Val irrespective of their angiotensin I-converting enzyme inhibitory
      activity. The effect was endothelium-independent, and was closely associated with
      vascular responses in the vascular smooth muscle layer.

PMID- 16960367
TI  - Structure of the hydrolyzed product (F-2) released from gamma-polyglutamic acid
      by gamma-glutamyl hydrolase YwtD of Bacillus subtilis.
AB  - The structure of the hydrolyzed product (F-2) with a molecular mass of about 2
      kDa released from gamma-polyglutamic acid by the gamma-glutamyl hydrolase YwtD of
      Bacillus subtilis was analyzed. The results showed that F-2 is an optically
      heterogeneous polymer consisting of D- and L-glutamic acid in an 80:20 ratio with
      D-glutamic acid on both the N- and C-terminal sides, suggesting that YwtD is an
      enzyme that cleaves the gamma-glutamyl bond between D- and D-glutamic acid
      recognizing adjacent L-glutamic acid toward the N-terminal region.

PMID- 16960368
TI  - Red potato extract protects from D-galactosamine-induced liver injury in rats.
AB  - The protective effects of red potato extract (RPE) as to liver damage were
      determined in D-galactosamine (GalN)-intoxicated rats. Increases in serum
      aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase
      activities, all of which were induced by GalN injection, decreased in RPE
      administered rats, suggesting that RPE acts as a functional food showing anti
      hepatotoxicity.

PMID- 16960369
TI  - Analysis of antioxidant activities contained in the Boesenbergia pandurata
      Schult. Rhizome.
AB  - The rhizome of Boesenbergia pandurata Schult. was found to possess potent
      antioxidant activity in a rat brain homogenate model. Bioassay-guided isolation
      of the active compounds from a CH2Cl2-MeOH (1:1) extract led to the isolation of
      5-hydroxy-7-methoxyflavanone, panduratin A, 5,7-dihydroxyflavanone, 2',6'
      dihydroxy-4'-methoxychalcone, 2',4'-dihydroxy-6'-methoxychalcone, and 4
      hydroxypanduratin A. Panduratin A, 4-hydroxypanduratin A, and 2',6'-dihydroxy-4'
      methoxychalcone were also found to exert neuroprotective effects.

PMID- 16960370
TI  - Kinetics of renin inhibition by sodium houttuyfonate analogs.
AB  - A series of chemical analogs of sodium houttuynin, the major constituent in the
      volatile oil of the perennial plant Houttuynia cordata Thunb, were studied for in
      vitro inhibition of renin activity. At a reaction concentration of 0.196 mg/ml,
      each of the sodium houttuynin analogs (SHAs), viz., hexanoyl acetal sodium
      sulfite (SHA-C6), octanoyl acetal sodium sulfite (SHA-C8), decanoyl acetal sodium
      sulfite (SHA-C10), dodecanoyl acetal sodium sulfite (SHA-C12) and tetradecanoyl
      acetal sodium sulfite (SHA-C14), inhibited renin activity up to 34.37%, 44.03%,
      79.33%, 83.04%, and 93.19% respectively. The IC50 values (the concentration of
      SHA that is required to reduce renin activity by 50%) of the most potent analogs
      were 273, 195, and 44 microM for SHA-C10, SHA-C12, and SHA-C14 respectively.
      Kinetic studies with SHA-14 indicated a linear mixed-type of enzyme inhibition
      with a Ki value of 45.35 microM. It was concluded that the SHAs constitute
      potentially useful ingredients for the formulation of antihypertensive products.

PMID- 16960371
TI  - Cloning, expression, and identification of genes involved in the conversion of DL
      2-amino-Delta2-thiazoline-4-carboxylic acid to L-cysteine via S-carbamyl-L
      cysteine pathway in Pseudomonas sp. TS1138.
AB  - Two novel genes (tsB, tsC) involved in the conversion of DL-2-amino-Delta2
      thiazoline-4-carboxylic acid (DL-ATC) to L-cysteine through S-carbamyl-L-cysteine
      (L-SCC) pathway were cloned from the genomic DNA library of Pseudomonas sp.
      TS1138. The recombinant proteins of these two genes were expressed in Escherichia
      coli BL21, and their enzymatic activity assays were performed in vitro. It was
      found that the tsB gene encoded an L-ATC hydrolase, which catalyzed the
      conversion of L-ATC to L-SCC, while the tsC gene encoded an L-SCC amidohydrolase,
      which showed the catalytic ability to convert L-SCC to L-cysteine. These results
      suggest that tsB and tsC play important roles in the L-SCC pathway and L-cysteine
      biosynthesis in Pseudomonas sp. TS1138, and that they have potential applications
      in the industrial production of L-cysteine.

PMID- 16960372
TI  - Cathepsin L plays an important role in the lysosomal degradation of L-lactate
      dehydrogenase.
AB  - A cystatin alpha-sensitive cysteine proteinase that plays an important role in
      the lysosomal inactivation and degradation of L-lactate dehydrogenase (LDH) was
      purified by column chromatography from an ammonium sulfate precipitate of
      lysosome extract prepared from rat livers. It was eluted with marked delay from
      cathepsins B and H in a Sephacryl S-200 column by its specific interaction with
      the gel, and then effectively separated from cathepsins B and H and other
      proteins. It was eluted with 0.5 M NaCl after washing with 0.2 M NaCl in a CM
      Sephadex column, indicating that it showed the same elution behavior as cathepsin
      L from the CM-Sephadex column. It had activity to hydrolyze z-Phe-Arg-NH-Mec, a
      synthetic substrate for cysteine proteinases, including cathepsins B and L. The N
      terminal sequences of the final preparation of LDH-inactivating enzyme were
      identical with those of rat cathepsin L. Inactivation and degradation of LDH by
      the final preparation were observed and effectively inhibited by a low level of
      cystatin alpha as well as a general cysteine proteinase inhibitor, leupeptin or
      (L-3-trans-carboxyoxirane-2-carbonyl)-L-leucine (3-methylbutyl)amide (E-64-c).
      From these results, it is concluded that cathepsin L plays a critical role in the
      lysosomal degradation of native LDH.

PMID- 16960373
TI  - Retinoic acid improves a hybridoma culture in a fructose-based medium by up
      regulation of fructose incorporation via retinoid nuclear receptors.
AB  - Fructose was focused on as an alternative sugar source to glucose in a hybridoma
      culture medium because it decreases lactate production during cultivation,
      leading to cell and product stability. But, not all human hybridoma cell lines
      grew well in a fructose-based serum-free medium. We found that the addition of
      all-trans-retinoic acid to the fructose-based medium improved the growth and
      monoclonal antibody production of hybridoma cell lines by up-regulation of
      fructose incorporation that represented increased expression of the fructose
      transporter, GLUT5. Selective activation of retinoid nuclear receptor by
      synthetic ligands showed that both retinoic acid receptors and retinoid X
      receptors might be related to the improvement of the fructose-based hybridoma
      culture. This study might be applicable to cell cultures susceptible to lactate
      and pH changes as well as hybridoma cultures.

PMID- 16960374
TI  - Alteration of coenzyme specificity of lactate dehydrogenase from Thermus
      thermophilus by introducing the loop region of NADP(H)-dependent malate
      dehydrogenase.
AB  - Previously we found that replacement of seven amino acid residues in a loop
      region markedly shifted the coenzyme specificity of malate dehydrogenase from
      NAD(H) toward NADP(H). In the present study, we replaced the seven amino acid
      residues in the corresponding region of an NAD(H)-dependent lactate dehydrogenase
      with those of NADP(H)-dependent malate dehydrogenase, and examined the coenzyme
      specificity of the resulting mutant enzyme. Coenzyme specificity was
      significantly shifted by 399-fold toward NADPH when k cat/Km(coenzyme) was used
      as the measure of coenzyme specificity. The effect of the replacements on
      coenzyme specificity is discussed based on in silico simulation of the three
      dimensional structure of the lactate dehydrogenase mutant.

PMID- 16960375
TI  - Cloning and expression of a mannose-binding jacalin-related lectin from leaves of
      Japanese cycad (Cycas revoluta Thunb.).
AB  - Cycad leaf lectin (CRLL), a mannose-recognizing jacalin-related lectin (mJRL),
      was first cloned as a gymnosperm lectin and expressed. The cDNA sequence of CRLL
      (DDBJ, accession no. AB198328), coding 291 amino acid residues, has a tandem
      repeat of about 150 amino acids divided into N- and C-terminal domains as
      Japanese chestnut mJRL. Sequence alignment showed deletion and insertion of the
      sequence, and its putative carbohydrate-binding sites showed some differences
      from other JRLs. PCR analysis showed that this lectin was expressed in the cycad
      leaf but not in the root or seed. Recombinant CRLL (rCRLL) was expressed in
      Escherichia coli and purified by affinity chromatography after refolding
      procedures. Properties of active rCRLL appeared to be almost the same as those of
      native CRLL.

PMID- 16960376
TI  - Characterization of the AP endonucleases from Thermoplasma volcanium and
      Lactobacillus plantarum: Contributions of two important tryptophan residues to AP
      site recognition.
AB  - Escherichia coli AP endonuclease (ExoIII) and its human homolog (APE1) have the
      sole tryptophan residue for AP site recognition (AP site recognizer) but these
      residues are at different positions near the catalytic sites. On the other hand,
      many bacterial AP endonucleases have two tryptophan residues at the same
      positions of both ExoIII and APE1. To elucidate whether these residues are
      involved in AP site recognition, the ExoIII homologs of Thermoplasma volcanium
      and Lactobacillus plantarum were characterized. These proteins showed AP
      endonuclease and 3'-5'exonculease activities. In each enzyme, the mutations of
      the tryptophan residues corresponding to Trp-280 of APE1 caused more significant
      reductions in activities and binding abilities to the oligonucleotide containing
      an AP site (AP-DNA) than those corresponding to Trp-212 of ExoIII. These results
      suggest that the tryptophan residue corresponding to Trp-280 of APE1 is the
      predominant AP site recognizer, and that corresponding to Trp-212 of ExoIII is
      the auxiliary recognizer.

PMID- 16960377
TI  - Exploring amino acids responsible for the temperature profile of glycoside
      hydrolase family 45 endoglucanase EGL3 from Humicola grisea.
AB  - EGL3 and RCE1 are glycoside hydrolase family 45 endoglucanases isolated from
      Humicola grisea and Rhizopus oryzae respectively. The amino acid sequences of the
      two endoglucanases are homologous; on the other hand, the optimum temperature of
      EGL3 is higher than that of RCE1. In this study, four chimeric endoglucanases,
      named ER1, ER2, ER3 and ER4, in which one of four sequential amino acid regions
      of the EGL3 catalytic domain (CAD) was replaced by the corresponding RCE1 amino
      acids, were constructed to explore the region responsible for the EGL3
      temperature profile. Then their temperature profiles were compared with that of
      the recombinant EGL3. Replacement of the N-terminal region of EGL3 with that of
      RCE1 caused the EGL3 temperature profile to shift to a lower temperature. These
      results suggest that the N-terminal amino acids of the EGL3 are responsible for
      the EGL3 temperature profile.

PMID- 16960378
TI  - Cytolytic toxin Cyt1Aa of Bacillus thuringiensis synergizes the mosquitocidal
      toxin Mtx1 of Bacillus sphaericus.
AB  - Using the shuttle vector pBU4, the mosquitocidal toxin gene mtx1 from Bacillus
      sphaericus strain SSII-1 was introduced into an acrystalliferous strain of B.
      thuringiensis both individually and in combination with the accessory protein
      gene p20 and the cytolytic protein gene cyt1Aa from B. thuringiensis subsp.
      israelensis. Bioassay results indicated that the recombinants B-pMT4(Mtx1) and B
      pMT9(Mtx1), both individually containing mtx1, had moderate toxicities to binary
      toxin susceptible and binary toxin resistant Culex quinquefasciatus larvae during
      the vegetative growth stage, but that their toxicities declined rapidly during
      the sporulation phase. The LC50 values were 2.5 and 4.8 mg/ml respectively,
      against 3-4 instar susceptible and resistant larvae for the final sporulated
      cultures of recombinants B-pMT9(Mtx1), and little toxicity was detected for B
      pMT4(Mtx1). Meanwhile, the recombinant B-pMPX2(Mtx1+Cyt1Aa) expressing Mtx1, P20
      alone, and Cyt1Aa in combination had stable toxicities during both the vegetative
      phase and the sporulation phase, with a LC50 ranging from 0.45-0.58 mg/ml.
      Furthermore, expression of Cyt1Aa appeared to enhance the activity of Mtx1 to
      target mosquito larvae, suggesting a synergism between Cyt1Aa and Mtx1 toxins.

PMID- 16960380
TI  - Absolute configuration of volicitin from the regurgitant of lepidopteran
      caterpillars and biological activity of volicitin-related compounds.
AB  - Volicitin [N-(17-hydroxylinolenoyl)-L-glutamine] and N-linolenoyl-L-glutamine are
      known as insect-produced plant volatile elicitors. The absolute configuration of
      the hydroxylinolenoyl moiety of volicitin from three noctuid species, Helicoverpa
      armigera, Mythimna separata and Spodoptera litura, was determined to be all 17S
      in high enantiomeric excess. When treated with 30 pmol of (17S)- and (17R)
      volicitin, corn seedlings were induced to release volatiles, there being no
      significant difference in the amount released between the two isomers. On the
      other hand, N-linolenoyl-L-glutamine was only about 30% as active as volicitin.
      Among several synthesized N-linolenoylamino acid conjugates, only the L-glutamine
      conjugate induced the emission of volatile organic compounds. These results show
      that the L-glutamine moiety of volicitin played a more critical role than the
      hydroxyl moiety, although both moieties affected the elicitor activity inducing
      the release of volatiles.

PMID- 16960379
TI  - Oxidative stress induces phosphoenolpyruvate carboxykinase expression in H4IIE
      cells.
AB  - Oxidative stress is closely associated with diabetes and is a major cause of
      insulin resistance. Impairment of hepatic insulin action is thought to be
      responsible for perturbations in hepatic glucose metabolism. In this study, we
      found that oxidative stress is involved in the dysregulation of gene expression
      of phosphoenolpyruvate carboxykinase (PEPCK), a key gluconeogenic enzyme, by a
      mechanism independent of insulin. Elevation of oxidative stress by injection of
      ferric nitrilotriacetate in rats increased the expression of hepatic PEPCK mRNA.
      To examine the direct action of oxidative stress on PEPCK expression, we treated
      H4IIE hepatoma cells with buthionine sulfoximine (BSO), an inhibitor of
      glutathione synthesis. BSO increased intracellular oxidative stress and the
      expression of PEPCK mRNA. Inhibition of p38 mitogen-activated protein kinase (p38
      MAP kinase), which mediates responses to oxidative stress, suppressed the
      induction of PEPCK mRNA by BSO. These results suggest that oxidative stress
      dysregulates hepatic PEPCK expression by an insulin-independent mechanism.

PMID- 16960381
TI  - Antioxidant and alpha-amylase inhibitory compounds from aerial parts of Varthemia
      iphionoides Boiss.
AB  - Various extracts of aerial parts of Varthemia (Varthemia iphionoides Boiss) were
      investigated for radical-scavenging activity, antioxidative activity, and porcine
      pancreas alpha-amylase inhibitory activity. The ethanol and water extracts showed
      a pronounced 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity,
      with inhibition of about 90% at a concentration of 100 microg/ml, and alpha
      amylase inhibitory activity of about 70% at a concentration of 200 microg/ml by
      the 2-chloro-4-nitrophenyl alpha-maltotrioside (CNP-G3) degradation method. The
      ethanol extract was purified by column chromatography to give seven 3
      methoxyflavones (1-7) and eudesmane sesquiterpene, selina-4,11(13)-dien-3-on-12
      oic acid (8). The structures of these compounds were established by NMR, MS, and
      UV spectroscopy. Of 3-methoxyflavones, 5,7,4'-trihydroxy-3,6-dimethoxyflavone
      (1), 5,7,4'-trihydroxy-3,3'-dimethoxyflavone (2), and 5,4'-dihydroxy-3,7,3'
      trimethoxyflavone (3,7,3'-tri-O-methyl-quercetin) (7) exhibited pronounced
      radical-scavenging activity. The antioxidative activity in the linoleic acid
      system was considerable in compounds 1, 2, and 5,4'-dihydroxy-3,6,7
      trimethoxyflavone (4). Compounds 1, 2, 4, 5 (5,7,4'-trihydroxy-3-methoxyflavone),
      and 6 (5,4'-dihydroxy-3,7-dimethoxyflavone) showed markedly high inhibitory
      activity against porcine pancreas alpha-amylase. Eudesmane sesquiterpene did not
      show any activity.

PMID- 16960382
TI  - Late type apoptosis and apoptosis free lethal effect of quercetin in human
      melanoma.
AB  - No satisfactory treatment is currently available for metastatic malignant
      melanoma. Recently, the flavonoid quercetin was suggested as a potential
      treatment due to its anti-tumorogenic properties. Some of these properties
      appeared to correspond to those published for UVB irradiation. To determine
      quercetin's long-term effects, type of apoptosis, and shared properties with UVB,
      we exposed Mel-Juso, M14, and G361 human melanoma cell-lines to a large range of
      quercetin or UVB doses, 20-400 microm and 25-1000 mJ/cm2 respectively. Apoptosis
      was measured for 4 consecutive d by flow cytometry and cell viability was studied
      by colony-forming assay. Quercetin decreased cell viability level in a dose
      dependent manner to almost zero at 100 microm. Up to this concentration, it did
      not induce significant apoptosis nor did it decrease the survival-fractions below
      90% during a 4 d follow-up. The data suggest that Quercetin is lethal to melanoma
      cells at concentrations that do not activate apoptosis during the first 4 d post
      exposure and that quercetin's effects extend beyond the period of direct contact.
      Both quercetin and UVB induced late-type apoptosis at the upper range of the
      tested doses, but they do not appear to share all the pathways that they
      activate. Finally, this paper provides novel data showing that quercetin causes
      two different lethal effects on human melanoma cells, suggesting the activation
      of at least two different dose-depended mechanisms.

PMID- 16960383
TI  - Molecular cloning, functional expression, and tissue distribution of a potato
      sprout allene oxide synthase involved in a 9-lipoxygenase pathway.
AB  - Potato (Solanum tuberosum) plants are rich in 9-lipoxygenase, which converts
      linoleic acid and alpha-linolenic acid to 9S-hydroperoxy-10E,12Z-octadecadienoic
      acid (9-HPOD) and 9S-hydroperoxy-10E,12Z,15Z-octadecatrienoic acid (9-HPOT)
      respectively. The allene oxide synthase (AOS) involved in 9-HPOD/9-HPOT
      metabolism in potato, however, has not been characterized in detail. We cloned a
      cDNA encoding a novel AOS from potato sprouts by reverse transcriptase-PCR based
      on a partial sequence in the EST database. This AOS was successfully expressed in
      the yeast Pichia pastoris, and purified using Ni-NTA resin. The recombinant
      enzyme metabolized 9-HPOD, 9-HPOT, 13-HPOD, and 13-HPOT with reaction
      efficiencies of 2.5 x 10(7), 1.0 x 10(7), 2.5 x 10(6), and 7.6 x 10(6) M(-1) s(
      1) respectively. The alpha-ketol formed from 9-HPOD was composed mainly of the 9R
      enatimomer (90%). Besides sprouts, the mRNA of this AOS was detected in buds,
      flowers, and stems, but not in leaves, tubers, or roots of mature plants,
      suggesting that this enzyme has a tissue-specific function.

PMID- 16960384
TI  - Endogenous prostaglandins E2 and F 2alpha serve as an anti-apoptotic factor
      against apoptosis induced by tumor necrosis factor-alpha in mouse 3T3-L1
      preadipocytes.
AB  - Adipocytes can function as endocrine cells secreting a variety of adipocytokines
      including tumor necrosis factor (TNF)-alpha. Treatment of cultured mouse 3T3-L1
      preadipocytes with TNF-alpha induced apoptosis, as was evident from increases in
      nuclear condensation and caspase-3 activity, but differentiated adipocytes during
      the maturation phase showed resistance to apoptosis by TNF-alpha. Antioxidants
      effectively reduced TNF-alpha-induced apoptosis in preadipocytes, indicating the
      involvement of reactive oxygen species. Exposure of preadipocytes to calcium
      ionophore A23187 reduced TNF-alpha-induced apoptosis, which was accompanied by
      increased production of prostaglandins (PGs) E2 and PGF 2alpha. TNF-alpha
      preferentially promoted gene expression of cyclooxygenase (COX)-2 without
      affecting that of COX-1. Consistently, NS-398, a COX-2 inhibitor, stimulated TNF
      alpha-induced apoptosis, which was reversed by exogenous PGE2 and PGF 2alpha.
      These results indicate that endogenous PGE2 and PGF 2alpha synthesized by
      preadipocytes through the induction of COX-2 can serve as anti-apoptotic factors
      against apoptosis by TNF-alpha.

PMID- 16960385
TI  - Development of a colorimetric assay for determining the amount of H2O2 generated
      in tobacco cells in response to elicitors and its application to study of the
      structure-activity relationship of flagellin-derived peptides.
AB  - Plants exhibit various defense responses after recognizing elicitor molecules
      derived from pathogenic microorganisms and host plants. In this study, we
      developed an improved colorimetric assay for quantifying the generation of H2O2
      in plant cells, one of the defense responses, to evaluate elicitor activity
      quantitatively. H2O2 is detected using a dye, N-(carboxymethylaminocarbonyl)-4,4'
      bis(dimethylamino)-diphenylamine sodium salt (DA-64), which can be measured by
      conventional spectrometers in a highly sensitive and quantitative manner. Using
      this method, we successfully measured the elicitor activity of flagellin-derived
      peptides in cultured tobacco cells, and identified several structural features of
      the peptides important for the elicitor activity. The results suggest that the
      structural factors required for expression of the elicitor activity differ
      slightly among plant species. The efficient and sensitive assay developed in this
      study should be useful not only for studying structure-activity relationships,
      but also for the screening of novel compounds that can induce defense responses.

PMID- 16960386
TI  - Immunostimulation effect of jellyfish collagen.
AB  - Certain edible large jellyfishes belonging to the order Rhizostomeae are consumed
      in large quantities in China and Japan. The exumbrella part of the edible
      jellyfish Stomolophus nomurai was cut and soaked in dilute hydrochloric acid
      solution (pH 3.0) for 12 h, and heated at 121 degrees C for 20 min. The
      immunostimulation effects of the jellyfish extract were examined. The jellyfish
      extract enhanced IgM production of human hybridoma HB4C5 cells 34-fold. IgM and
      IgG production of human peripheral blood lymphocytes (PBL) were also accelerated,
      2.8- and 1.4-fold respectively. Moreover, production of interferon (IFN)-gamma
      and tumor necrosis factor (TNF)-alpha by human PBL was stimulated 100- and 17
      fold respectively. Collagenase treatment inactivated the immunostimulation
      activity of the jellyfish extract. In addition, purified collagen from bovine
      Achilles' tendon accelerated IgM production of hybridoma cells. These facts mean
      that collagen has an immunostimulation effect, and that the active substance in
      jellyfish extract is collagen.

PMID- 16960387
TI  - Beta-carotene modulates the immunological function of RAW264, a murine macrophage
      cell line, by enhancing the level of intracellular glutathione.
AB  - The activities of beta-carotene on redox status and the immune functions of
      RAW264 cells, a murine macrophage cell line, were investigated. Supplementation
      with beta-carotene for RAW264 cells resulted in apparently inconsistent redox
      indices: lipid peroxidation was enhanced but intracellular oxidation was
      moderately attenuated. Attenuated intracellular oxidation was endorsed by an
      increase in glutathione accompanied by up-regulated transcription of a subunit of
      gamma-glutamylcysteine synthetase, the rate-limiting enzyme for glutathione
      synthesis. alpha-Tocopherol, which can quench lipid peroxidation by free radical,
      neither inhibited that by beta-carotene nor influenced the intracellular redox
      status. Lipopolysaccharide-stimulated transcriptions of IL-1beta and IL-12 p40 in
      RAW264 were inhibited by beta-carotene but not by alpha-tocopherol. These results
      indicate that beta-carotene, which can modulate the intracellular redox status of
      macrophages by enhancing the level of intracellular glutathione, is related to
      the immune functions of macrophages.

PMID- 16960388
TI  - Protective effect of grape seed polyphenols against high glucose-induced
      oxidative stress.
AB  - We aimed to clarify whether grape seed polyphenols (GSPs) are candidates
      therapeutic agents against diabetes mellitus, and to determine what degree of GSP
      oligomerization has the most potent efficacy. We studied the protective effects
      of various molecular weight GSPs (monomer, oligomer, polymer, and oligonol) on
      high glucose-induced cytotoxicity. In the present study, a high concentration of
      glucose (30 mM) induced cytotoxicity and oxidative stress (reactive oxygen
      species and nitric oxide) in cultured LLC-PK1 cells, but treatment with GSPs,
      especially oligomer GSPs, had potent protective effects against high glucose
      induced oxidative stress. In addition, high glucose induced nuclear translocation
      of nuclear factor-kappa B, and increased expression of cyclooxygenase-2,
      inducible nitric oxide synthase, and bax, but GSP treatment inhibited them. These
      results indicate that GSPs have protective effects against high glucose-induced
      cytotoxicity, and among them, oligomer GSPs have more potent effects than other
      GSPs (monomer, polymer, and oligonol) on high glucose-induced renal cell damage.

PMID- 16960389
TI  - Effect of sorbed water on the thermal stability of soybean protein.
AB  - A soybean protein isolate (SPI), and its beta-conglycinin and glycinin componets
      were obtained from defatted soybean flour by applying dissolution and
      precipitation based on the difference in their solubility depending on each
      isoelectric point. The purity evaluated by SDS-PAGE of the beta-conglycinin and
      glycinin preparations was about 84% and 80%, respectively, resulting in a clear
      difference in the pH dependence on solubility. A BET plot derived from the water
      sorption isotherm at 25 degrees C showed that the amount of the monolayer
      adsorption of these preparations was about 6-9%, the value for the beta
      conglycinin preparation being about 1.5 times higher than that for the glycinin
      preparation. The beta-conglycinin and glycinin preparations were respectively
      denatured at around 75 degrees C and 86 degrees C in the presence of excess
      water, whereas the denaturation temperature of both preparations was markedly
      increased by decreasing sorbed water content below 40%, corresponding well with
      the unfrozen water content.

PMID- 16960390
TI  - Comparative effect of gromwell (Lithospermum erythrorhizon) extract and borage
      oil on reversing epidermal hyperproliferation in guinea pigs.
AB  - To compare the systemic efficacy of borage oil (Borago officinalis: BO) and
      gromwell (Lithospermum erythrorhizon), two plant species of the Boraginaceae
      family, epidermal hyperproliferation was induced in guinea pigs by a hydrogenated
      coconut oil diet for 8 weeks. Subsequently, guinea pigs were fed diets of BO
      (group HBO), organic extract (group HGO), or water extract (group HGW) of
      gromwell for 2 weeks. In groups HGO and HGW, proliferation scores and the level
      of ceramides, the major lipid maintaining epidermal barrier, were similar with
      those in normal control group BO fed BO diet for 10 weeks. Despite accumulation
      of 15-hydroxyeicosatrienoic acid (15-HETrE), the potent anti-proliferative
      metabolite of gamma-linolenic acid (GLA: major polyunsaturated fatty acid in BO),
      the reversal of epidermal hyperproliferation and the ceramide level of group HBO
      were less than those of groups HGO and HGW. Taken together, our data demonstrate
      that gromwell is more effective in reversing epidermal hyperproliferation with a
      marked increase in ceramides.

PMID- 16960391
TI  - Effects of dietary D-psicose on diurnal variation in plasma glucose and insulin
      concentrations of rats.
AB  - The effects of supplemental D-psicose in the diet on diurnal variation in plasma
      glucose and insulin concentrations were investigated in rats. Forty-eight male
      Wistar rats were divided into four groups. Each group except for the control
      group was fed a diet of 5% D-fructose, D-psicose, or psico-rare sugar (3:1
      mixture of D-fructose and D-psicose) for 8 weeks. Plasma glucose levels were
      lower and plasma insulin levels were higher at all times of day in the psicose
      and psico-rare sugar groups than in the control and fructose groups. Weight gain
      was significantly lower in the psicose group than in the control and fructose
      groups. Liver glycogen content, both before and after meals was higher in the
      psicose group than in the control and fructose groups. These results suggest that
      supplemental D-psicose can lower plasma glucose levels and reduce body fat
      accumulation. Hence, D-psicose might be useful in preventing postprandial
      hyperglycemia in diabetic patients.

PMID- 16960392
TI  - CYP724B2 and CYP90B3 function in the early C-22 hydroxylation steps of
      brassinosteroid biosynthetic pathway in tomato.
AB  - We characterized a new cytochrome P450 monooxygenase (P450), CYP724B2, from
      tomato (Lycopersicon esculentum). CYP724B2 showed 42% and 62% amino acid sequence
      identity with Arabidopsis DWARF4/CYP90B1 and rice DWARF11/CYP724B1 respectively.
      Functional assay of CYP724B2 heterologously expressed in insect cells revealed
      that CYP724B2 catalyzes C-22 hydroxylation of campesterol, indicating that
      CYP724B2 is a C-22 hydroxylase. We also isolated a tomato CYP90B homolog
      (CYP90B3) and found that CYP90B3 is a C-22 hydroxylase as well. CYP724B2 and
      CYP90B3 showed substrate specificities similar to each other toward the
      biosynthetic intermediate compounds from campesterol to campestanol. Campesterol
      was the best substrate, and (24R)-ergost-4-en-3-one was also metabolized to the C
      22 hydroxylated product to some extent. On the other hand, the P450s catalyzed C
      22 hydroxylation of (24R)-5alpha-ergostan-3-one and campestanol at a trace level,
      indicating that the compounds after C-5alpha reduction are poor substrates of
      CYP724B2 and CYP90B3. In addition, cholesterol (C27 sterol) and sitosterol (C29
      sterol) were also converted to C-22 hydroxylated products by the P450s.
      Furthermore, CYP724B2 and CYP90B3 genes were ubiquitously expressed, and their
      transcript levels were down-regulated by the exogenous application of
      brassinolide. These findings strongly suggest that CYP724B2 and CYP90B3 function
      in the early C-22 hydroxylation steps of brassinosteroid biosynthetic pathway in
      tomato.

PMID- 16960393
TI  - RNA interference effectively inhibits mRNA accumulation and protein expression of
      hepatitis C virus core and E2 genes in human cells.
AB  - RNA interference (RNAi) has been widely used for the analysis of gene function
      and represents a new promising approach to develop effective antiviral drugs. In
      this study, several small interfering RNAs (siRNAs) corresponding to two
      structural genes (core and E2) of hepatitis C virus (HCV) were designed and in
      vitro transcribed to explore the possibility of silencing these two genes. The
      plasmids pEGFP-C and pEGFP-E2, which contain the EGFP reporter gene and the core
      or E2 gene as silencing targets, were co-transfected with siRNAs into HEK 293T
      cells. At various time points of post-transfection, core and E2 expression levels
      were detected by fluorescence microscopy, flow cytometry, Western blotting, and
      real-time quantitative PCR. The results showed that the mean fluorescence
      intensity, protein expression, and RNA transcripts of siRNAs transfected cells
      were significantly reduced. This may provide an approach for the development of
      novel prophylactic or therapeutic agents for HCV infection.

PMID- 16960394
TI  - Salicylic acid and a chitin elicitor both control expression of the CAD1 gene
      involved in the plant immunity of Arabidopsis.
AB  - The Arabidopsis mutant cad1 (constitutively activated cell death 1) shows a
      phenotype that mimics hypersensitive response (HR)-like cell death. The CAD1
      gene, which encodes a protein containing a domain with significant homology to
      the MACPF (membrane attach complex and perforin) domain of complement components
      and perforin, is likely to control plant immunity negatively and has a W-box cis
      element in its promoter region. We found that expression of the CAD1 gene and
      other W-box containing genes, such as NPR1 and PR2, was promoted by salicylic
      acid (SA) and benzothiadiazole (BTH) as a SA agonist. The CAD1 gene was also
      stimulated by a purified chitin oligosaccharide elicitor (degree of
      polymerization = 8). This latter control was not under SA, because CAD1
      expression was not suppressed in 35SnahG transgenic plants, which are unable to
      accumulate SA. These expression profiles were confirmed by promoter analysis
      using pCAD1::GUS transgenic plants. The CAD1 expression promoted by BTH and the
      chitin elicitor was not suppressed in the npr1 mutant, which is insensitive to SA
      signaling. These results indicate that the CAD1 gene is regulated by two distinct
      pathways involving SA and a chitin elicitor: viz., SA signaling mediated through
      an NPR1-independent pathway, and chitin elicitor signaling, through an SA
      independent pathway. Three CAD1 homologs that have multiple W-box elements in
      their promoters were also found to be under the control of SA.

PMID- 16960395
TI  - Selection of CC chemokine receptor 5-binding peptide from a phage display peptide
      library.
AB  - Human CC chemokine receptor (CCR) 5 is a G protein-coupled receptor involved in a
      broad range of human diseases that mediates HIV-1 viral entry into cells. Certain
      small molecule receptor antagonists to CCR5 have been useful in therapy for these
      diseases. In this study, CCR5-expressing CHO cells (CHO/CCR5 cells) were used to
      select CCR5-binding peptides from a phage-displayed 12-mers peptide library. All
      of the 30 clones selected from the library showed specific binding to CHO/CCR5
      cells by enzyme linked immunosorbent assay (ELISA). Seventeen out of the 30
      clones shared the amino acid motif AFDWTFVPSLIL. The motif-containing phages and
      synthetic peptide AFDWTFVPSLIL blocked the binding of mAb 2D7 to CHO/CCR5 cells
      and competitively inhibited the ability of chemokine regulated on activation
      normal T cell expressed and secreted (RANTES) binding to CHO/CCR5 cells.
      Furthermore, the peptide AFDWTFVPSLIL also inhibited RANTES induced increase in
      the intracellular Ca2+ level in CHO/CCR5 cells. These results suggest that the
      peptide AFDWTFVPSLIL was specific for CCR5 and that it might become a CCR5
      antagonist.

PMID- 16960396
TI  - Anti-tumor activities of the antlered form of Ganoderma lucidum in allogeneic and
      syngeneic tumor-bearing mice.
AB  - We investigated the anti-tumor effects of a dry powder preparation of the
      antlered form of Ganoderma lucidum (G. lucidum AF, rokkaku-reishi in Japanese), a
      variant type of G. lucidum, not only in allogeneic Sarcoma 180-bearing ddY mice,
      but also in syngeneic MM 46-bearing C3H/He mice. G. lucidum AF inhibited tumor
      growth and elongated the life span when orally administered to mice by free
      feeding of a 2.5% G. lucidum AF-containing diet. It also showed anti-tumor
      activity in spite of post-feeding after tumor inoculation. G. lucidum AF
      significantly countered the depression of splenic CD8+ cells and protected the
      decrease in interferon-gamma (IFN-gamma) production in regional lymph nodes of MM
      46-bearing mice, indicating that the anti-tumor activity of G. lucidum AF might
      be caused by its immunostimulating action. These results suggest that the
      ingestion of G. lucidum AF can be useful for the prevention and curing of cancer.

PMID- 16960397
TI  - Kallmann syndrome phenotype in a female patient with CHARGE syndrome and CHD7
      mutation.
AB  - We report on a 14 7/12-year-old Japanese female patient with CHARGE syndrome and
      CHD7 mutation who also exhibited Kallmann syndrome (KS) phenotype. She had poor
      pubertal development and apparently impaired sense of smell. A GnRH test showed
      severely compromised responses of LH (<0.5 --> <0.5 IU/L) and FSH (<0.5 --> 1.2
      IU/L), and magnetic resonance imaging delineated hypoplastic olfactory bulbs.
      Mutation analysis revealed a heterozygous nonsense mutation at exon 33 of CHD7
      (7027C>T, Q2343X). The results provide further support for the notion that KS
      phenotype can be included in the phenotypic spectrum of CHARGE syndrome, and
      indicate that CHARGE syndrome with KS phenotype is caused by a CHD7 mutation.

PMID- 16960398
TI  - Sporadic congenital hyperthyroidism due to a germline mutation in the thyrotropin
      receptor gene (Leu 512 Gln) in a Japanese patient.
AB  - Constitutively activating thyrotropin receptor (TSHR) germline mutations have
      been identified as a molecular cause of congenital hyperthyroidism. We here
      describe a Japanese woman who had presented with severe hyperthyroidism and
      advanced bone age as a neonate. She underwent neurosurgical intervention for
      craniosynostosis, and presented with perodactylia and mild mental retardation
      with hydrocephalus. Hyperthyroidism has been refractory to antithyroid drug
      therapy in the absence of antithyrotropin receptor antibodies during follow-up of
      20 years, resulting in an enlarged goiter. Analysis of the patient's genomic DNA
      showed a heterozygous thymine-to-adenine point mutation in exon 10 of TSHR at
      position 1535 which was not present in the parents' DNA. This mutation, changing
      leucine to glutamine in codon 512 in the third transmembrane region, was
      previously identified as a somatic mutation in toxic thyroid nodules and was
      shown to increase basal cAMP production in vitro. To our knowledge, this is the
      first report of a germline mutation of TSHR causing sporadic congenital
      nonautoimmune hyperthyroidism in a Japanese patient.

PMID- 16960399
TI  - Adiponectin and insulin resistance in young and healthy smokers.
AB  - Smoking is closely associated with insulin resistance, though the mechanism is
      not clear. Adiponectin, a novel anti-atherosclerotic and anti-inflammatory
      adipose tissue product, which is closely associated with insulin resistance, was
      reported to be low in smokers with cofactors for atherosclerosis. However, the
      effects of smoking on circulating adiponectin levels in otherwise healthy people
      are unknown. In this study, a case control design was implemented to search for
      the effect of smoking on plasma adiponectin and insulin sensitivities in healthy
      people. Sixty-four healthy male smokers, with no family history of hypertension
      and diabetes mellitus were compared with appropriate 36 age and body mass index
      matched controls. Both the patients and controls were the soldiers of a troop
      with regular daily physical activity. Plasma adiponectin, high sensitive C
      reactive protein (hsCRP), insulin and lipid levels, and insulin sensitivity as
      assessed by homeostasis model assessment index (HOMA) of the smokers were
      measured and compared with those of the controls. The plasma adiponectin, hsCRP,
      insulin levels and HOMA indexes of the two groups were similar. These parameters
      were not affected by the amount of cigarettes per day. HDL-cholesterol levels
      were lower (p = 0.01) and systolic blood pressures were higher (p = 0.02) in the
      smokers. These results indicate that smoking may not affect plasma adiponectin
      and insulin levels in young and healthy men with high exercise capacity.

PMID- 16960400
TI  - Vitamin D, osteoclastogenesis and bone resorption: from mechanistic insight to
      the development of new analogs.

PMID- 16960401
TI  - Management of differentiated thyroid carcinoma with radioiodine and recombinant
      human TSH.
AB  - Recombinant human TSH (rhTSH) brought revolutionary change in the management of
      patients with differentiated thyroid cancer since it was first approved for
      clinical use in the United States and Europe. Follow-up management of
      differentiated thyroid cancer is based on the detection of recurrent or residual
      cancer, traditionally achieved by measurement of serum thyroglobulin level and
      various imaging techniques including 131I whole body scan. Previously, TSH
      stimulation was achieved only by induction of hypothyroidism following withdrawal
      of thyroid hormone. However, hypothyroidism is uncomfortable and is association
      with a reduction in quality of life. RhTSH can provide elevated TSH without
      making patients hypothyroid. In the United States and Europe, rhTSH is approved
      for use only in monitoring of differentiated thyroid cancer. In this article, we
      reviewed the role of rhTSH in the diagnosis and management of differentiated
      thyroid cancer.

PMID- 16960402
TI  - Extrapancreatic proinsulin/insulin-expressing cells in diabetes mellitus: is
      history repeating itself?
AB  - Insulin is a key regulator of life. Until 25 years ago, the pancreatic beta-cell
      was thought to be the only organ that produces insulin in the body. Insulin
      deficiency, whether absolute (in type 1) or relative (in type 2 diabetes),
      underlies the metabolic derangements in diabetes mellitus, and investigations on
      insulin have concentrated on pancreatic insulin production, its regulation and
      the metabolic consequences of insulin deficiency. The thymus was the next organ
      that was found to also produce insulin, a process that may tolerize the body to
      the molecule, protecting the host from developing autoimmune beta-cell
      destruction and (type 1) diabetes. However, now and then there were descriptions
      of promiscuous insulin production outside the pancreas. During our investigations
      on diabetes gene therapy in rodents, we serendipitously came across the presence
      of mysterious cells marked by proinsulin production in unexpected organs, some of
      which cells may underlie certain chronic diabetic complications. Starting with a
      historical perspective on insulin expression in brain and thymus, this review
      focuses mainly on unraveling the mystery of extrapancreatic extrathymic
      proinsulin/insulin expression in diabetes mellitus.

PMID- 16960403
TI  - Japanese patients with acute myocardial infarction who present without chest
      pain.
AB  - Previous studies have suggested that patients with acute myocardial infarction
      (AMI) who presented without chest pain had an unfavorable prognosis due to
      undertreatment. Despite this, few studies have been conducted on the topic,
      particularly in Japan. The present analysis aimed at determining whether Japanese
      AMI patients without chest pain are undertreated and experience higher mortality
      during hospitalization. Data from the Tokai Acute Myocardial Infarction Study II
      sample were used, which is a prospective study of all consecutive patients
      admitted to the 15 acute care hospitals in the Tokai region with the diagnosis of
      AMI from 2001 to 2003. Data on baseline and procedural characteristics and
      hospital outcome were collected. Differences in the baseline and procedural
      characteristics and clinical outcomes between patients presenting with and
      without chest pain were assessed. We evaluated a total of 1,769 patients who
      presented with chest pain and 452 who did not. The patients with AMI in the
      absence of chest pain were older and were more likely to have worse clinical
      conditions than those with chest pain. They were more likely to be undertreated,
      although the probability of vasopressor use was higher. The patients without
      chest pain had a significantly higher in-hospital mortality rate than those with
      chest pain. According to multivariate analysis, however, chest pain was not
      identified as an independent predictor of in-hospital death. The results suggest
      that the higher in-hospital mortality rate among Japanese AMI patients without
      chest pain could be accounted for by differences in clinical conditions.

PMID- 16960404
TI  - A computer based telemedicine protocol to predict acute coronary syndrome in
      patients with chest pain at home.
AB  - The decision to admit a patient to a coronary care unit for acute coronary
      syndrome (ACS) has serious medical and financial consequences. In this study, we
      aimed to develop a computer program to predict the existence of ACS in patients
      with chest pain at home; it is intended that patients will be able to access the
      program via the website to test its validity. This study proceeded in two phases.
      In the first phase, a computer-based decision protocol was developed using
      recursive-partitioning analysis to predict ACS in 250 patients with chest pain on
      the basis of their historical data. In the second phase, this protocol was tested
      in 115 patients for diagnosis of ACS prospectively. Thirty-two of the patients
      answered the algorithm questions on the website. All of the patients who visited
      the website of this study were advised to go to the emergency department.
      Although the algorithm showed the presence of ACS in 82 of 115 patients, 60 of
      115 patients were diagnosed as having ACS in the emergency department (n = 55) or
      at follow-up. The agreement between the diagnosis of the algorithm and the true
      diagnosis was moderate and statistically significant (Kappa coefficient 0.61, P <
      0.001). The sensitivity of the algorithm was 100%, although its specificity was
      60%. The accuracy of the algorithm in diagnosing ACS was 81%. The algorithm
      diagnoses patients with ACS at a high ratio and decreases the number of patients
      being unnecessarily admitted to the emergency with non-ACS.

PMID- 16960405
TI  - Re-elevation of high-sensitivity C-reactive protein but not the von Willebrand
      Factor after withdrawing atorvastatin therapy in patients with unstable angina
      undergoing coronary artery stenting.
AB  - Statins are known to reduce high-sensitivity C-reactive protein (hs-CRP)
      concentrations and improve endothelial function. However, whether statin
      withdrawal causes re-elevated concentrations of hs-CRP and von Willebrand Factor
      (vWF) (a marker of endothelial damage) remains unknown. We hypothesized that the
      concentrations of hs-CRP and vWF are substantially increased in patients with
      unstable angina pectoris (UAP) and noticeably decreased following coronary
      stenting along with atorvastatin therapy. However, re-elevations of these
      biomarker concentrations occurred once again after withdrawing atorvastatin
      therapy. We serially examined the plasma concentrations of hs-CRP and vWF in 51
      patients with UAP before (day 0) and after (days 21, 90, 180, 270) performing
      coronary artery stenting. The concentrations of these 2 biomarkers were also
      measured in 30 healthy control subjects. Patients were treated with atorvastatin
      (40 mg/day orally) for 180 days, after which the therapy was withdrawn. The hs
      CRP and vWF concentrations were significantly higher in the patients than in the
      healthy control subjects before the procedure (both P values < 0.001). The hs-CRP
      concentration decreased significantly on day 21 (P < 0.001), and further to a
      substantially lower level on day 180 (P < 0.0001). However, the hs-CRP level
      significantly increased again on day 270, as compared with that on day 180 (P <
      0.001). The vWF plasma concentration decreased gradually to a significantly lower
      level on day 180. The concentration of this biomarker did not differ between days
      180 and 270. In conclusion, although hs-CRP concentrations decreased markedly
      following combined stenting and atorvastatin therapy, re-elevation after
      atorvastatin therapy was withdrawn in UAP patients undergoing coronary stenting
      was not observed. Conversely, restoration of endothelial function was slow and
      persistent in these patients.

PMID- 16960407
TI  - Contrast-enhanced magnetic resonance and thallium scintigraphy in the detection
      of myocardial viability: a prospective comparative study.
AB  - The aim of the present study was to prospectively compare contrast-enhanced
      magnetic resonance imaging (CE-MRI) with single-photon emission tomography using
      (201)Thallium chloride (SPECT Tl) in the detection of myocardial viability.
      Patients with chronic coronary artery disease and systolic dysfunction defined by
      an ejection fraction (EF) <or= 45% were included. CE-MRI was performed 10-15
      minutes after the administration of a gadolinium-based contrast agent using an
      Inversion Recovery Turbo FLASH (fast low-angle shot) sequence. A 4-hour rest
      redistribution protocol was used for SPECT Tl. Radionuclide ventriculography was
      used for the assessment of EF. Forty patients with an EF of 33.1 +/- 7.7% were
      included. Thirty-two underwent a follow-up examination after revascularization.
      Comparison of viability assessment was performed in 1360 segments. Agreement was
      noted in 1065 (78.3%) segments, resulting in a kappa value of 0.336.
      Discrepancies were observed in 96 SPECT Tl viable segments that were described as
      nonviable according to CE-MRI and in 199 SPECT Tl nonviable segments that were
      viable in the CE-MRI study. In patients undergoing the follow-up examination, EF
      increased by 5.5 +/- 7.3% (33.6 +/- 8.6% to 39.2 +/- 9.7%), but the relation
      between the amount of dysfunctional viable myocardium defined by both methods
      studied and the change in EF after revascularization was very weak and not
      statistically significant. Moderate agreement in the myocardial viability
      assessment between CE-MRI and SPECT Tl was observed. CE-MRI seems to be more
      accurate in identifying myocardial viability in inferior and inferolateral
      segments. We were unable to verify if either of the methods studied is useful for
      the prediction of EF improvement after revascularization.

PMID- 16960406
TI  - Presence and severity of Chlamydia pneumoniae and Cytomegalovirus infection in
      coronary plaques are associated with acute coronary syndromes.
AB  - Although an association between Chlamydia pneumoniae (Cpn) or Cytomegalovirus
      (CMV) infection and coronary atherosclerosis has been reported, such an
      association is less clear for acute coronary syndromes (ACS). The purpose of this
      study was to investigate the pathogenic roles of Cpn and CMV infection of
      coronary plaques in ACS. We divided 38 coronary plaque specimens obtained from 38
      patients who underwent directional coronary atherectomy or thrombectomy into an
      ACS group (n = 21) and a non-ACS group (n = 17). Cpn and CMV in specimens were
      stained using immunohistochemical techniques and analyzed quantitatively. The
      detection rate for either Cpn- or CMV-positive cells in ACS patients was slightly
      higher compared with non-ACS patients. Detection rates for both Cpn- and CMV
      positive cells were significantly higher in ACS patients than in non-ACS patients
      (P = 0.010). Furthermore, the density of Cpn- and CMV-positive cells in plaques
      was significantly higher in ACS patients than in non-ACS patients (P < 0.003).
      The results indicate that the presence and severity of Cpn and CMV infection in
      coronary plaques are greater in patients with ACS compared with non-ACS patients.
      We conclude that infection with Cpn and CMV in coronary plaques may be involved
      in the pathogenesis of ACS.

PMID- 16960408
TI  - Clinical reliability of the 6 minute corridor walk test performed within a week
      of a myocardial infarction.
AB  - The 6 minute walk test (6 MWT) has been shown to provide a clinically useful
      index of functional capacity in chronic heart failure. We hypothesized that
      similar results would be found in patients who had a recent (ie, within a week)
      myocardial infarction (MI). Twenty-five patients (23 males, aged 43 to 72 years)
      who had undertaken an exercise stress test without complications underwent 3
      consecutive 6 MWTs (1 hour apart). Heart rate, systolic and diastolic blood
      pressure, the level of perceived exertion (Borg scale), and the walking distance
      were determined. In addition, chest pain was assessed by a 0 to 10 numerical
      rating scale (NRS) and the ECG was continuously monitored. All subjects were able
      to successfully complete the exercise tests without major cardiovascular
      complications: mild chest pain (NRS 1 to 3) was found in 3 patients. A Bland
      Altman analysis revealed that the mean bias +/- 95% confidence interval of the
      differences on distance walked between test 2 - test 1 were substantially higher
      than test 3 - test 2 differences (18 +/- 66 m and 6 +/- 41 m, respectively). The
      intraclass correlation coefficients were consistently high for all physiological
      and sensorial responses at the end of the 6 MWTs (range, 0.75 to 0.95). The 6 MWT
      is a safe and reproducible measurement of functional capacity in stable patients
      after a noncomplicated MI, even when performed within a week of the event.
      Therefore, this test might be useful for the evaluation of exercise tolerance in
      phases I and II of inpatient cardiovascular rehabilitation programs or to assess
      functional responses to selected interventions.

PMID- 16960409
TI  - Frequency of Brugada-type ECG pattern (Brugada sign) in Southern Turkey.
AB  - The frequency of Brugada sign was found to differ among ethnic groups. Yet, there
      is no data regarding the prevalence of Brugada syndrome and sign in our country.
      The aim of this study was to determine the frequency of a Brugada-type
      electrocardiogram (ECG) pattern in southern Turkey. A total of 1,238 subjects
      (males, 671, females, 567) were included in the study. The previously archived
      ECGs of 807 subjects without any evidence of structural heart disease were chosen
      randomly and evaluated. In addition, prospective analysis of the ECGs of 431
      subjects (males, 293, females, 138) randomly chosen from healthy university
      students were also included. The mean age was 38.9 +/- 17.6 years. Six subjects
      (0.48%) had a Brugada-type ECG pattern. One (0.08%) of them had the coved-type
      and 5 (0.40%) had the saddleback-type. All subjects were asymptomatic. A Brugada
      type ECG pattern was obtained in 1 (0.17%) female and in 5 (0.74%) males (OR: 4.2
      CI: 0.5-36.4, P = 0.2). The Brugada-type ECG pattern frequency was 0.12% in
      subjects >or= 25 years old and 1.16% in subjects between 17-24 years old (OR: 9.4
      CI: 1.1-81.2, P = 0.02). Young males between 17-24 years had the highest (1.70%)
      frequency. The results indicate that the frequency of the Brugada-type ECG
      pattern was 0.48% in the general population, being more prevalent in young males
      in our region. These results are similar to the findings of studies performed in
      other countries.

PMID- 16960410
TI  - Longitudinal age-related changes in 24-hour total heart beats and premature beats
      and their relationship in healthy elderly subjects.
AB  - The aim of this study was to conduct a longitudinal follow-up on age-related
      changes in 24-hour total heart beats (THBs) and total premature beats and their
      correlations in healthy elderly subjects. In 15 healthy elderly subjects (mean
      age, 70.0 +/- 4.1, age range at 1st recording, 64 to 80 years, 10 females, 5
      males), we conducted Holter monitoring twice at an interval of 15 years and
      analysed age-related changes in THBs, atrial premature beats (APBs), and
      ventricular premature beats (VPBs), as well as their correlations. The results
      indicated that THBs, APBs, and VPBs all significantly increased with age in the
      healthy elderly subjects at a mean age of 70.0 +/- 4.1 (THB: 91074.1 +/- 11515.3
      versus 99457.5 +/- 12131.0; P = 0.0004, APB:119.2 +/- 97.8 versus 884.4 +/-
      1193.8; P = 0.0008, VPB: 15.2 +/- 53.6 versus 140.7 +/- 228.9; P = 0.0328).
      Moreover, we divided the subjects into increase and nonincrease groups based on
      the age-related changes in APB and VPB for 15 years ([n]; Inc-APB: Noninc-APB = 6
      : 9, Inc-VPB: Noninc-VPB = 5 : 10). In the increase groups, premature beats
      tended to increase in proportion to changes in THBs with age (APB: Y = 207.488 +
      0.136 X, r = 0.848, P = 0.0303; VPB: Y = -27.594 + 0.028 X, r = 0.727, P =
      0.1921). In conclusion, this 15-year follow-up of Holter recordings in healthy
      elderly subjects revealed that THBs, APBs, and VPBs increased with age, and that
      the increases in premature beats, especially APBs, were in proportion to those in
      THBs.

PMID- 16960411
TI  - Effects of carvedilol therapy on arrhythmia markers in patients with congestive
      heart failure.
AB  - The aim of this study was investigate the effects of carvedilol therapy on
      ventricular repolarization characteristics as assessed by QT dispersion (QTd) and
      heart rate variability (HRV) in patients with heart failure. Thirty-one patients
      with heart failure (mean age, 63.9 years) were included in the study. Carvedilol
      was administered in addition to standard therapy for CHF at a dose of 6.25 mg/day
      and uptitrated to the maximum tolerated dose. Control group consisted of 14
      patients with heart failure (mean age, 69.4 years) who could not take carvedilol
      due to several reasons. All patients were followed-up 6 months. QT dispersion
      (QTd), and corrected QTd (QTcd) values were calculated at baseline and at the end
      of follow-up. Time domain and frequency domain heart rate variability analysis
      were performed with ambulatory Holter ECG. Mean carvedilol dose was 23.9 +/- 13.9
      mg. Significant reductions were observed in the QTd (P = 0.016) and QTcd (P =
      0.001) with carvedilol therapy, whereas QTd (P = 0.47) and QTcd (P = 0.43) did
      not change significantly in the control group. The QT maximum value did not
      change significantly but the QT minimum value (P = 0.03) was significantly
      increased after carvedilol therapy. Although the mean SDANN value was improved (P
      = 0.039), other HRV parameters such as mean SDNN (P = 0.32), rMSSD (P = 0.74),
      and the LF/HF ratio (P = 0.35) did not change significantly after carvedilol
      therapy. This prospective controlled study shows that carvedilol therapy
      decreased QT dispersion and improved ventricular repolarization characteristics
      but did not change autonomic dysfunction in patients with heart failure.

PMID- 16960412
TI  - Factors for weaning from a percutaneous cardiopulmonary support system (PCPS) in
      patients with severe cardiac failure: a comparative study in weaned and nonweaned
      patients.
AB  - The percutaneous cardiopulmonary support system (PCPS) has been widely accepted
      for the treatment of patients with severe cardiac failure. This system, which
      uses Seldinger's method through a percutaneous approach, enables rapid
      application in emergency situations. However, the indication for deployment and
      discontinuation of PCPS has not yet been established. We evaluated the results of
      PCPS use for the treatment of patients with severe cardiac failure and
      investigated factors that would predict successful weaning from PCPS. A total of
      32 patients (23 men and 9 women) who had PCPS for the treatment of severe cardiac
      failure between January 1997 and October 2004 were retrospectively reviewed. The
      mean age of the patients was 57 +/- 17 years (range, 14 to 78 years). PCPS was
      necessary for severe cardiac failure after cardiac surgery in 15 patients,
      pulmonary infarction in 4, acute myocardial infarction in 3, acute myocarditis in
      3, and other causes in 7. The mean duration of PCPS support in all 32 patients
      was 134 +/- 117 hours (range, 8 to 532). Twelve patients (38%) could be weaned
      from PCPS (group A), while the remaining 20 patients (62%) could not (group B).
      The incidence of cardiac arrest prior to PCPS use (n = 10, 31%) was significantly
      (P < 0.05) lower in group A (1/12, 8%) than in group B (9/20, 45%). There were
      significant differences in the APACHE II scores, urine output, serum lactate
      levels, and epinephrine and dopamine dose received from PCPS induction to 72
      hours after PCPS use between the 2 groups (P < 0.05). Multivariate logistic
      regression analysis showed that an episode of cardiac arrest prior to PCPS
      induction was the only significant predictor for the unsuitability for
      discontinuation of PCPS. This retrospective study showed the limitation of PCPS
      therapy for patients with an episode of cardiac arrest who did not show
      improvement in their APACHE II score, urine output, serum lactate levels, and
      catecholamine dose received within 72 hours after PCPS induction. These results
      may help formulate criteria for indication and discontinuation of PCPS for
      patients with severe cardiac failure.

PMID- 16960413
TI  - Temporal variations at the onset of spontaneous acute aortic dissection.
AB  - There have only been a few studies of the chronobiological occurrence of acute
      aortic dissection (AAD), and most were international and multicentered. The aim
      of the present study, conducted at only one center, was to determine the most
      frequent daily, monthly, and seasonal occurrences of AAD. The study population
      included 204 patients (66.5% male) treated at our institute between January 1,
      1998 and January 1, 2004. A significantly higher frequency of AAD occurred from
      6:00 AM to 12:00 noon, compared with other time periods (P < 0.001). The results
      showed a significant circadian variation in AAD (P < 0.001) with a peak between
      9:00 AM and 10:00 AM. No significant variation was found for the day of the week;
      however, AAD occurred most frequently on Wednesday and Monday. The frequency of
      AAD was found to be significantly higher during winter versus other seasons (P <
      0.001). The analysis of monthly variations of the onset of AAD confirmed a peak
      in February (12.9%) and in January (12.3%). Similar to other cardiovascular
      diseases, AAD exhibits significant circadian and seasonal/monthly variations. Our
      findings indicate that the prevention of AAD, especially during the
      aforementioned vulnerable periods, is possible by adequate tailoring of the
      treatment of hypertension, which is the main AAD predisposing factor.

PMID- 16960414
TI  - Effects of intravenous lidocaine on QTd and HRV changes due to tracheal
      intubation during sevoflurane induction.
AB  - The aim of the present study was to evaluate the effects of IV lidocaine on
      autonomic cardiac function changes in tracheal intubation (TI) during sevoflurane
      anaesthesia by using more reliable parameters, namely, the analysis of QT
      dispersion and heart rate variability (HRV) from Holter monitoring. In this
      prospective, double-blind study, 44 American Society of Anaesthesiologists class
      I-II patients scheduled for hysterectomy were randomly and equally divided into 2
      groups; a control sevoflurane group (group S, n = 22) and a lidocaine sevoflurane
      group (group LS, n = 22). Before the induction of anaesthesia, the
      electrocardiograms (ECG) of all patients were recorded for 3 minutes as baseline
      parameters. In both groups, the anaesthesia was induced with 7% sevoflurane in
      O(2 )at 6L min(-1) via a facemask for 2 minutes. However, before the induction of
      sevoflurane anaesthesia in group LS, 1 mg kg(-1) of lidocaine was given
      intravenously (IV). For muscle relaxation during TI, vecuronium was given to all
      participants. Three minutes after administration of vecuronium, TI was performed
      and an ECG was recorded synchronously for another 3 minutes. The results from the
      later records were used as postintubation parameters. Baseline and postintubation
      data were analysed. When compared to baseline values, postintubation LF/HF and
      SDNN values were increased in group S (P = 0.005, P = 0.001, respectively),
      whereas postintubation LF and HF values were decreased in group LS (P = 0.014, P
      = 0.041, respectively). Under the influence of sevoflurane anaesthesia, TI
      resulted in sympathetic activation. However, this activation was attenuated by
      the administration of IV 1 mg kg(-1) lidocaine 5 minutes prior to TI.

PMID- 16960415
TI  - Carvedilol prevents myocardial fibrosis in hamsters.
AB  - The objective of the present study was to determine if carvedilol protects
      against myocardial degeneration and fibrotic change, and reduces mortality in TO2
      hamsters. Carvedilol was administered intraperitoneally to 8 week-old TO2
      hamsters for 21 weeks at a dose of 11 mg/kg/day. There were 15 TO2 hamsters in
      the carvedilol group (group C) and 10 in the untreated group (group N). The
      control group consisted of 11 Fb hamsters (group F). The mortality rate was
      determined from the number of surviving hamsters after 29 weeks. Myocardial
      fibrosis was evaluated by MRI and histopathological examination. EF and LVDd were
      determined by echocardiography at 8 and 29 weeks, while the MRI score was
      calculated at 29 weeks. Mortality, histopathological fibrosis, and MRI score were
      all lower in group C than in group N. Carvedilol had a protective effect against
      myocardial fibrosis and decreased the mortality rate in TO2 hamsters.

PMID- 16960416
TI  - The genesis of injury potentials: the role of recording electrodes at different
      locations.
AB  - The objective of the present study was to elucidate the mechanisms underlying the
      so-called injury potentials, including the origin of monophasic action potentials
      and the role of recording electrodes. Two-dimensional computer simulation was
      performed for cardiac tissue containing an inactivated region due to high
      extracellular K concentration. Myocardial activation was reproduced using a
      membrane model. The bidomain model was utilized for the calculation of intra-and
      extracellular potentials. A bipolar lead from electrodes at injured and intact
      regions showed a monophasic curve corresponding to the transmembrane potential of
      the fiber under the electrode of the intact region. Unipolar leads from injured
      and intact regions showed monophasic and biphasic curves, respectively. Lowering
      the extracellular conductivity was associated with an increase in the wave
      amplitude. The injured region of myocardium was associated with monophasic
      potential variations. A bipolar lead with electrodes at injured and intact
      regions reflected the activity of the intact region.

PMID- 16960417
TI  - Myocyte morphological characteristics differ between the phases of pulmonary
      hypertension-induced ventricular hypertrophy and failure.
AB  - Pulmonary hypertensive model rats were prepared by treating them with
      monochrotaline (MCT). Using these model rats, we examined myocyte remodeling in
      the right ventricle in response to increased right ventricular pressure. Male
      Sprague-Dawley rats were divided into 2 groups. Group M received MCT and group C
      received physiological saline. The 2 groups were examined at weeks 2, 5, and 7
      after MCT or saline injection, respectively. At week 2, a significant difference
      in cell form was not observed in either group. At week 5, cell volume and myocyte
      cross-sectional area (CSA) of the right ventricle in group M were significantly
      greater than those in group C. At week 7, cell volume, CSA, and cell length of
      the right ventricle in group M were all significantly greater than those in group
      C. These results suggest that pulmonary hypertension causes hypertrophy,
      accompanying the enlargement of CSA in the right ventricle, and that cells
      lengthen in the phase of right ventricular failure. These results are similar to
      the changes observed in left ventricular myocytes due to overload pressure. Both
      right and left ventricular myocytes may share a common mechanism for myocyte
      remodeling as an adaptive and maladaptive response to increased ventricular
      pressure.

PMID- 16960418
TI  - A case of blunt chest trauma induced acute myocardial infarction involving two
      vessels.
AB  - Blunt chest trauma rarely induces acute myocardial infarction. We report a 36
      year-old man who suffered from blunt trauma to the anterior chest wall while
      operating a punching machine. This case is the first report of simultaneous blunt
      chest trauma to the left anterior descending artery and left circumflex artery.
      The patient was treated surgically and discharged without any serious sequela.
      Early detection of the lesion site is important with regard to selecting the
      appropriate treatment strategy in patients with coronary injury caused by blunt
      chest trauma. Routine 12-lead electrocardiography and serial cardiac enzyme
      evaluation are necessary in every patient with chest trauma because they supply
      crucial information about the extent of cardiac damage. Treatment with primary
      angioplasty or bypass surgery should be based on the characteristics of the
      lesion and the associated problem.

PMID- 16960419
TI  - 18F-fluorodeoxyglucose positron emission tomography in a case of retroperitoneal
      fibrosis.
AB  - A patient with recurrent abdominal pain was admitted to our hospital. Computed
      tomography showed a soft dense mass surrounding the abdominal aorta at the
      infrarenal level, which was compatible with retroperitoneal fibrosis. (18)F
      fluorodeoxyglucose ((18)F-FDG) positron emission tomography showed abnormal
      uptake of (18)F-FDG into these lesions. Two months after the initiation of
      corticosteroid therapy, the abnormal uptake of (18)F-FDG had ceased along with a
      reduction in the fibrous mass surrounding the abdominal aorta.

PMID- 16960420
TI  - alpha7 Nicotinic acetylcholine receptor stimulation inhibits lipopolysaccharide
      induced interleukin-18 and -12 production in monocytes.
AB  - Nicotine inhibited interleukin (IL)-18 and -12 production in lipopolysaccharide
      (LPS)-stimulated monocytes, and the action of nicotine was antagonized by a non
      selective and a selective alpha7 nicotinic acetylcholine receptor (alpha7-nAChR)
      antagonist, suggesting that the stimulation of alpha7-nAChR may be involved in
      the action of nicotine. Nicotine is reported to induce prostaglandin E(2)
      (PGE(2)) production in monocytes through the up-regulation of cyclooxygenase
      (COX)-2 expression. PGE(2) is known to increase cAMP levels and to activate
      protein kinase A (PKA). COX-2 and PKA inhibitors prevented the action of
      nicotine, indicating that the mechanism of action of nicotine may be via
      endogenous PGE(2) production.

PMID- 16960421
TI  - Inhibition by SEA0400, a selective inhibitor of Na+/Ca2+ exchanger, of Na+ 
      dependent Ca2+ uptake and catecholamine release in bovine adrenal chromaffin
      cells.
AB  - The effects of SEA0400, a selective inhibitor of the Na(+)/Ca(2+) exchanger
      (NCX), on Na(+)-dependent Ca(2+) uptake and catecholamine (CA) release were
      examined in bovine adrenal chromaffin cells that were loaded with Na(+) by
      treatment with ouabain and veratridine. SEA0400 inhibited Na(+)-dependent
      (45)Ca(2+) uptake and CA release, with the IC(50) values of 40 and 100 nM,
      respectively. The IC(50) values of another NCX inhibitor KB-R7943 were 1.8 and
      3.7 microM, respectively. These results indicate that SEA0400 is about 40 times
      more potent than KB-R7943 in inhibiting NCX working in the reverse mode. In
      intact cells, SEA0400 and KB-R7943 inhibited CA release induced by acetylcholine
      and DMPP. The IC(50) values of SEA0400 were 5.1 and 4.5 microM and the values of
      KB-R7943 were 2.6 and 2.1 microM against the release induced by acetylcholine and
      DMPP, respectively, indicating that the potency of SEA0400 is about a half of
      that of KB-R7943 in inhibiting the nicotinic receptor-mediated CA release. The
      binding of [(3)H]nicotine with nicotinic receptors was inhibited by SEA0400
      (IC(50) = 90 microM) and KB-R7943 (IC(50) = 12 microM). From these results, it is
      concluded that unlike KB-R7943, SEA0400 has a potent and selective action on NCX
      in bovine adrenal chromaffin cells.

PMID- 16960422
TI  - Skin tests of a novel nicotine patch, PHK-301p, in healthy male volunteers: phase
      I, placebo-controlled study.
AB  - Major local adverse reactions in the nicotine patches are skin reactions. To
      assess the skin reaction of PHK-301p, a newly developed nicotine patch, we
      conducted a phase I study that consisted of 2 parts: a skin irritation test (48-h
      closed patch test) and a photosensitivity test (24-h closed patch test +
      Ultraviolet A irradiation). Twenty healthy men were treated with PHK-301p and
      placebo. Both preparations were punched out to a circle of 6-mm diameter and were
      applied simultaneously to each participant. Skin irritation and photosensitivity
      were assessed by a physician who was kept unaware of the treatment. In the skin
      irritation test, moderate and mild erythemas were observed in each participant 72
      h after application (24 h after removal) for PHK-301p. Mild erythema was observed
      in one participant 49 h after application (1 h after removal) for placebo. The
      skin irritation index, which was calculated based on the skin reactions of
      participants, was 7.5 for PHK-301p and 2.5 for placebo. In the photosensitivity
      test, one participant had mild erythema (+/-) approximately 25 and 72 h after
      application of PHK-301p. No solar urticaria was observed. From these results, we
      concluded that PHK-301p is an acceptable product as a nicotine patch.

PMID- 16960423
TI  - Topics on the Na+/Ca2+ exchanger: role of vascular NCX1 in salt-dependent
      hypertension.
AB  - Excess salt intake is a major risk factor for hypertension. However, the
      molecular mechanisms underlying salt-dependent hypertension remain obscure. Our
      recent studies using selective Na(+)/Ca(2+) exchange inhibitors and genetically
      engineered mice provide compelling evidence that salt-dependent hypertension is
      triggered by Ca(2+) entry through Na(+)/Ca(2+) exchanger type 1 (NCX1) in
      arterial smooth muscle. Endogenous cardiac glycosides, which may contribute to
      salt-dependent hypertension, seem to be necessary for NCX1-mediated hypertension.
      Intriguingly, recent studies by Dostanic-Larson et al. using knock-in mice with
      modified cardiac glycoside binding affinity of Na(+),K(+)-ATPases demonstrate
      that this binding site plays an important physiological role in blood pressure
      control. Thus, when cardiac glycosides inhibit Na(+),K(+)-ATPase in arterial
      smooth muscle cells, the elevation of local Na(+) on the submembrane area is
      believed to facilitate Ca(2+) entry through NCX1, resulting in vasoconstriction.
      This proposed pathway may have enabled us to explain how to link dietary salt to
      hypertension.

PMID- 16960424
TI  - Topics on the Na+/Ca2+ exchanger: responses of Na+/Ca2+ exchanger to interferon
      gamma and nitric oxide in cultured microglia.
AB  - The Na(+)/Ca(2+) exchanger (NCX) plays a role in regulation of intracellular
      Ca(2+) levels, but little is known about the functional role of NCX in microglia.
      To clarify the role of NCX in microglia, we studied the responses of NCX to
      pathological conditions such as interferon-gamma or nitric oxide (NO) exposure.
      Treatment with interferon-gamma caused a biphasic increase in NCX activity. The
      delayed increase in NCX activity was accompanied by increases in the mRNA and
      protein levels. Pharmacological studies show that protein kinase C and tyrosine
      kinase are involved in the transient and delayed increases in NCX activity, and
      the extracellular signal-regulated protein kinase is involved in the delayed
      increase in NCX activity. On the other hand, NO causes apoptotic cell death in
      cultured microglia. We observed, using the specific NCX inhibitor SEA0400, that
      NO activates NCX activity and NCX is involved in NO-induced depletion of Ca(2+)
      in the endoplasmic reticulum (ER), leading to ER stress. These results suggest
      that NCX is involved in the regulation of Ca(2+) levels in the ER. The responses
      of NCX to interferon-gamma and NO implies that NCX plays a key role in microglial
      function.

PMID- 16960425
TI  - Topics on the Na+/Ca2+ exchanger: involvement of Na+/Ca2+ exchange system in
      cardiac triggered activity.
AB  - Sodium-calcium exchange (NCX) is one of the major regulators of intracellular
      Ca(2+) concentration in cardiac myocytes. The bi-directional and electrogenic
      property of NCX raises a question about whether NCX is involved in arrhythmias.
      We reviewed the role of NCX in cardiac triggered activity in limited experimental
      conditions: the digitalis-induced arrhythmia, the arrhythmia caused from
      sustained opening of sodium channel, and the arrhythmia caused from the
      inhibition of inwardly rectifying potassium current. Effects of NCX inhibitors on
      ventricular arrhythmias recorded on ECG or the delayed afterdepolarizations and
      triggered activity recorded by the current clamp method were evaluated. As an NCX
      inhibitor, we preferred to use SEA0400 instead of KB-R 7943. For a precise
      analysis, a computational reconstruction of action potential with the Luo and
      Rudy model was applied. The cardiac NCX system seems to play a role only in the
      digitalis-induced arrhythmia and may not be involved in other arrhythmias. This
      review highlights the relationship between triggered activity and an NCX system
      and also suggests the physiologic and pathologic aspect of the NCX system in
      cardiac arrhythmias.

PMID- 16960427
TI  - Influence of the dominant white/KIT genotypes on the reproductive organs of pigs.
AB  - Based on earlier studies with mice and pigs, the possible pleiotropic effects of
      the individual porcine Dominant White/KIT genotypes on the size, histological
      parameters, and surface features of the ovaries; on the size, histological
      characteristics, and volume of the testes; and on the occurrence of abnormal
      epididymal sperm cells were studied in two F2 generations of an intercross
      between Hampshire boars and Hungarian Large White sows. The KIT genotypes were
      determined by a PCR-RFLP method. The ovarian diameters of gilts of various KIT
      genotypes did not differ significantly (P=0.292), and the II pigs had the
      smallest diameters. The proportion of the investigated follicular types among the
      different KIT genotypes did not differ significantly (P=0.329-0.919), and the
      highest numbers of degenerated and atretic follicles were found in the ovaries of
      II genotype pigs, which also exhibited the highest proportion of primary
      follicles. The testis volume in the II homozygote white genotype boars (249.5
      cm(3)) was significantly (P<0.01) larger than in the Ii (205.4 cm(3)) and ii
      (197.5 cm(3)) boars. Bodyweight and age significantly (P<0.01) affected
      testicular volume. KIT genotypes had no profound effect on the proportion of the
      various epididymal sperm abnormalities, and ii type boars showed the highest
      (nonsignificant) numbers of primary abnormalities. The changes in abnormal sperm
      cell frequency were linear to the changes in bodyweight and testis volume. We
      were unable to demonstrate disadvantageous effects of the KIT genotypes on the
      investigated ovarian, testicular, and epididymal sperm characteristics. Therefore
      the reproductive traits of white colored pigs examined in this study are no worse
      than those of pigmented breeds.

PMID- 16960428
TI  - An organophosphate insecticide methyl parathion (o- o- dimethyl o-4-nitrophenyl
      phosphorothioate) induces cytotoxic damage and tubular atrophy in the testis
      despite elevated testosterone level in the rat.
AB  - Methyl parathion (MP) is an organophosphate pesticide used in agriculture,
      although quite often illegally used indoors to contain insects. The present study
      was planned to investigate the effects of MP on rat testis. Adult male Wistar
      rats (13-14 weeks) were treated with MP as follows. Experiment 1-0, 1.75, 3.5 or
      7 mg/kg i.p. for 5 days and sacrificed on Day 14; experiment 2 and 3- 0, 0.5, or
      1 mg/kg i.p. for 12 days, and sacrificed on Days 130 and 77, respectively;
      experiment 4- 0, 0.75, or 1.5 mg/kg i.p. for 25 days, and sacrificed on Day 17;
      experiment 5- 0 or 3.5 mg/kg po for 25 days, and sacrificed on Day 17, after the
      last exposure. MP decreased the body weight and the testis weight in experiments
      4 and 5 (p<0.05-0.001) due to decreased food intake and tubular atrophy
      respectively. MP increased the intra-testicular testosterone level and decreased
      the LH level in experiments 4 and 5. The seminiferous epithelium showed sloughing
      of germ cells, vacuoles, focal necrosis, and formation of multinucleated giant
      cells, cellular degeneration (nuclear pyknosis, halo appearance and shrinkage of
      nuclei) and tubular atrophy, especially in experiment 4. The degree of testicular
      damage was higher in experiment 4>5>1>3>2 indicating more effect of prolonged
      i.p. treatment. Homogenization-resistant spermatid count was decreased in
      experiments 1, 4 and 5, and MP also decreased the tubular diameter, and
      epithelial height (p<0.05-0.001). Incidences of stage XIV tubules, number of
      meiotic figures and elongating spermatids were also decreased, whereas the
      incidence of tubules showing epithelial sloughing increased (p<0.05-0.001). We
      conclude that MP is a reproductive toxicant in male rats which causes significant
      testicular damage in the testis.

PMID- 16960429
TI  - Effects of formalin-preservation on element concentrations in animal tissues.
AB  - Determination of the exposure level of environmental pollutants is essential in
      studies on environmental toxicology. If concentrations of exposed pollutants in
      tissues are not affected by formalin-preservation, a preserved specimen will
      provide not only histopathological information but also the exposure level of
      environmental pollutants. In the present study, concentrations of nine elements
      in the liver and kidney were compared between fresh and formalin- or neutral
      formalin-preserved specimens to validate the ultimate analysis of the preserved
      specimens. After one year of preservation, various elements had diffused from the
      specimens into the solutions. The concentrations of iron, copper, zinc (in the
      case of neutral formalin) and selenium in the central region of the specimens
      showed no alterations, suggesting that the diffusions of these elements were
      limited to the surface of the specimens. Therefore, preserved specimens may be
      available for the determination of these elements if the specimens are large
      enough for their surface to be removed. Concentrations of other elements in the
      preserved specimens were different from the original ones, because the diffusion
      or infiltration also occurred in the deep region of the specimens.

PMID- 16960430
TI  - Beneficial effect of moderate food restriction in toxicity studies in rats.
AB  - Moderate food restriction (FR) has been established as a nutritionally
      appropriate and well-controlled method with long-term beneficial effects in
      conducting toxicity and carcinogenicity studies in rodents. This study describes
      the early effects of moderate FR on toxicity study parameters in rats and on the
      variability of these parameters. Physical signs, body weight, food and water
      consumption, and clinical pathology parameters were examined in a 4-week study in
      which rats were moderately food-restricted or fed ad libitum (AL). There were no
      diet-related differences in physical signs, hematology or urinalysis. FR-related
      changes were observed in body weight and serum biochemistry; however, most of the
      changes involved anti-aging alterations and/or physiological adjustment to FR.
      Moderate FR resulted in low variability and good reproducibility in body weight.
      The present results indicate that moderate FR does not impair study parameters
      and increases statistical sensitivity. Therefore, a moderate FR feeding regimen
      is beneficial not only for long-term but also for short-term toxicity studies in
      rats.

PMID- 16960431
TI  - Involvement of Raf-1/MEK/ERK1/2 signaling pathway in zinc-induced injury in rat
      renal cortical slices.
AB  - Zinc is an essential nutrient that can also be toxic. We have previously reported
      that zinc-related renal toxicity is due, in part, to free radical generation in
      the renal epithelial cell line, LLC-PK(1) cells. We have also shown that an
      MEK1/2 inhibitor, U0126, markedly inhibits zinc-induced renal cell injury. In
      this study, we investigated the role of an upstream MEK/ERK pathway, Raf-1 kinase
      pathway, and the transcription factor and ERK substrate Elk-1, in rat renal
      cortical slices exposed to zinc. Immediately after preparing slices from rat
      renal cortex, the slices were incubated in medium containing Raf-1 and MEK
      inhibitors. ERK1/2 and Elk-1 activation were determined by Western blot analysis
      for phosphorylated ERK (pERK) 1/2 and phosphorylated Elk-1 (pElk-1) in nuclear
      fractions prepared from slices exposed to zinc. Zinc caused not only increases in
      4-hydroxynonenal (4-HNE) modified protein and lipid peroxidation, as an index of
      oxidant stress, and decreases in PAH accumulation, as that of renal cell injury
      in the slices. Zinc also induced a rapid increase in ERK/Elk-1 activity
      accompanied by increased expressions of pERK and pElk-1 in the nuclear fraction.
      A Raf-1 kinase inhibitor and an MEK1/2 inhibitor U0126 significantly attenuated
      zinc-induced decreases PAH accumulation in the slices. The Raf-1 kinase inhibitor
      and U0126 also suppressed ERK1/2 activation in nuclear fractions prepared from
      slices treated with zinc. The present results suggest that a Raf-1/MEK/ERK1/2
      pathway and the ERK substrate Elk-1 are involved in free radical-induced injury
      in rat renal cortical slices exposed to zinc.

PMID- 16960432
TI  - A reevaluation of the threshold exposure level of inhaled JP-8 in mice.
AB  - C57BL/6 mice were nose-only exposed to JP-8 jet fuel at average concentrations of
      45, 267, and 406 mg JP-8/m(3) for 1 hr/d for 7 days to further test the
      hypothesis that exposure to JP-8 concentrations below the current permissible
      exposure level (PEL) of 350 mg/m(3) will induce lung injury, and to validate a
      new "in-line, real-time" total hydrocarbon analysis system capable of measuring
      both JP-8 vapor and aerosol concentrations. Pulmonary function and respiratory
      permeability tests were performed 24 to 30 hr after the final exposures. No
      significant effects were observed at 45 or 267 mg/m(3). The only significant
      effect observed at 406 mg/m(3) was a decrease in inspiratory dynamic lung
      compliance. Morphological examination and morphometric analysis of distal lung
      tissue demonstrated that alveolar type II epithelial cells showed limited
      cellular damage with the notable exception of a significant increase in the
      volume density of lamellar bodies (vacuoles), which is indicative of increased
      surfactant production, at 45 and 406 mg/m(3). The terminal bronchial epithelium
      showed initial signs of cellular damage, but the morphometric analysis did not
      quantify these changes as significant. The morphometric analysis techniques
      appear to provide an increased sensitivity for detecting the deleterious effects
      of JP-8 as compared to the physiological evidence offered by pulmonary function
      or respiratory permeability tests. These observations suggest that the current
      350 mg/m(3) PEL for both JP-8 jet fuel and for other more volatile petroleum
      distillates should be reevaluated and a lower, more accurate PEL should be
      established with regard human occupational exposure limits.

PMID- 16960433
TI  - Effect of whole blood clotting time in rats with ionized hypocalcemia induced by
      rapid intravenous citrate infusion.
AB  - Although the toxic effects of citrate including hemodynamic and cardiovascular
      changes result from a decrease in ionized calcium levels in serum due to
      chelating action, these effects of citrate on blood coagulation have not yet been
      fully clarified. The present study examines whether serum citrate and ionized
      calcium levels affect whole blood clotting time in rats using the test tube
      method in which citrate is administered by rapid intravenous infusion. Citrate
      was infused via the tail vein into 10 rats at 3, 4 or 5 mmol/kg/hr for 1 hr, and
      then whole blood clotting time, serum citrate and ionized calcium levels were
      determined. Whole blood clotting time did not significantly change at citrate
      infusion rates of 3 and 4 mmol/kg/hr. However, at 5 mmol/kg/hr, whole blood
      clotting time was significantly prolonged by a factor of 2.1 relative to the
      untreated group, when the serum citrate level was 10.03 +/- 1.39 mmol/l (59.0
      fold higher than that in the untreated group) and the serum-ionized calcium level
      was 0.29 +/- 0.02 mmol/l (0.2-fold lower than that in the untreated group). These
      results suggest that whole blood clotting time is significantly prolonged in rats
      with severe ionized hypocalcemia.

PMID- 16960434
TI  - Alteration of 5-HIAA levels in frontal cortex and dorsal raphe nucleus in rats
      treated with combined administration of tryptophan and ethanol.
AB  - The present studies sought to investigate the effect of tryptophan alone or
      coadministration of tryptophan and ethanol on the interaction of central frontal
      cortex and dorsal raphe nucleus serotonergic functional activities by utilizing
      in vivo microdialysis. Tryptophan (50 mg/kg, i.p.) led to a significant increase
      in the levels of 5-HIAA, a metabolite of serotonin (5-HT), in the dorsal raphe
      nucleus, but not in the frontal cortex. Coadministration of tryptophan and
      ethanol caused very marked increases in 5-hydroxyindoleacetic acid (5-HIAA)
      levels in both the frontal cortex and the dorsal raphe nucleus, although ethanol
      (1.25 g/kg) did not change 5-HIAA levels in both areas. Moreover, the application
      of WAY100635 (10 muM), 5-HT(1A) antagonist, into the frontal cortex after
      coadministration caused a marked increase in 5-HIAA levels in the frontal cortex
      and a decrease in the levels in the dorsal raphe nucleus, although WAY100635
      alone had no effect on these levels. This may suggest that WAY100635-induced
      increase of 5-HIAA levels in the frontal cortex resulted from negative feedback
      following the blockade of serotonergic 5-HT(1A) autoreceptors, and that this
      increase in 5-HIAA levels decreased 5-HIAA levels in the dorsal raphe nucleus by
      preventing the activation of dorsal raphe 5-HT(1A) autoreceptors. WAY100635 into
      the dorsal raphe nucleus did not significantly change 5-HIAA levels in both
      areas. This may indicate that the blockade of dorsal raphe 5-HT(1A) autoreceptors
      by WAY100635 resulted in unchanged 5-HIAA levels in the frontal cortex.
      Behavioral sign of teeth-chattering was markedly observed following the
      coadministration and in combination with WAY100635. These results may suggest
      that the increased 5-HIAA levels in both areas after coadministration are
      indicative of the interrelation via activation of serotonergic neurons, and that
      the increased levels are partly responsible for behavioral activation of rats.

PMID- 16960435
TI  - Two-year feed study of carcinogenicity and chronic toxicity of ortho
      chloronitrobenzene in rats and mice.
AB  - Carcinogenicity and chronic toxicity of ortho-chloronitrobenzene (o-CNB) were
      examined by feeding groups of 50 F344 rats and 50 BDF(1) mice of both sexes o-CNB
      containing diets for 2 years. The dietary concentration of o-CNB was 0, 80, 400
      or 2000 ppm (w/w) for rats and 0, 100, 500 or 2500 ppm for mice. The 2-year
      administration of o-CNB produced a dose-dependent increase in incidences of
      hepatocellular adenomas and carcinomas in rats and mice of both sexes and
      hepatoblastomas in mice of both sexes. Incidences of altered cell foci in the
      liver were increased in the o-CNB-fed rats of both sexes. Metastasis from mouse
      malignant liver tumors occurred predominantly in the lung. The hepatocarcinogenic
      response to o-CNB was found to be more potent in mice than in rats. Marginally
      increased incidences of renal cell adenomas in the 2000 ppm-fed female rats and
      renal cell carcinomas in the 2000 ppm-fed male rats were noted, together with a
      significantly increased incidence of atypical tubule hyperplasias. Spontaneous,
      age-related chronic progressive nephropathy was exacerbated in a dose-related
      manner, and caused the death of 47 male rats fed 2000 ppm before the end of the 2
      year administration period. The highest dose levels of o-CNB except for the
      administration of 2000 ppm to male rats were thought to meet the criteria of the
      maximum tolerated dose set by both NCI and IARC guidelines. Causative factors of
      o-CNB-induced carcinogenicity were discussed with reference to our previous
      rodent studies of subchronic toxicity of o-CNB and carcinogenicity and chronic
      toxicity of para-chloronitrobenzene.

PMID- 16960436
TI  - Relationship between AUC of 5'-DFUR and toxicity of capecitabine,
      fluoropyrimidine carbamate analogs, and 5'-DFUR in monkeys, mice, and rats.
AB  - Capecitabine is an oral fluoropyrimidine carbamate which is converted to 5
      fluorouracil (5-FU) via 3 enzymatic step to 5'-deoxy-5-fluorocytidine (5'-DFCR),
      5'-deoxy-5-fluorouridine (5'-DFUR), and finally 5-FU. We performed 4-week
      toxicity studies of capecitabine (N(4)-pentyloxycarbonyl-5'-deoxy-5
      fluorouridine), galocitabine (trimethoxybenzyl-5'-deoxy-5-fluorocytidine), 4
      different fluoropyrimidine carbamate analogs (R=butyl, isopentyl, propyl, or
      phenethyl), and 5'-DFUR in cynomolgus monkeys with toxicokinetic measurements of
      intact molecules, 5'-DFCR, and 5'-DFUR. Four-week toxicity data for capecitabine
      in rats and mice were also obtained for comparison. Capecitabine, galocitabine,
      butyl, and isopentyl analogs showed similar toxicities in hematopoietic and
      intestinal organs at 1.0 mmol/kg and the AUCs of 5'-DFUR were approximately 40 to
      60 microg*hr/ml. These compounds showed slight toxicity at 0.5 mmol/kg and no
      toxicity at 0.1 mmol/kg, and AUCs of 5'-DFUR were approximately 30 and 5
      microg*hr/ml, respectively. Propyl and phenethyl analogs showed slight toxicity
      at 1.0 mmol/kg and no toxicity at 0.5 mmol/kg, and AUCs of 5'-DFUR were
      approximately 30 and 10 microg*hr/ml, respectively. On the other hand, severe and
      slight-to-moderate toxicity was observed at 0.5 and 0.25 mmol/kg in 5'-DFUR
      treated monkeys and AUCs of 5'DFUR were 35.6 and 5.2 microg*hr/ml, respectively.
      In mice and rats, the toxicity of capecitabine was less than in monkeys relative
      to dose, but 5'-DFUR AUCs were almost the same. In conclusion, 5'-DFUR AUC
      correlated with toxicity following oral administration of capecitabine and its
      analogs in monkeys, mice, and rats, although this relationship is not seen in
      humans. Capecitabine was less toxic in monkeys than oral 5'-DFUR according to
      dose (mmol/kg) and 5'-DFUR AUC.

PMID- 16960437
TI  - Cisplatin-induced expression of iron-retaining genes FIT2 and FIT3 in
      Saccharomyces cerevisiae.
AB  - cDNA microarray analysis indicated that mRNA levels of Fit2p and Fit3p, proteins
      involved in iron retention within the yeast cell wall, were markedly increased by
      treatment of Saccharomyces cerevisiae with cisplatin. Expression of FIT2 and FIT3
      is known to be transcriptionally regulated by Aft1p. Northern blotting
      demonstrated a time- and concentration-dependent increase in the mRNA levels of
      both proteins following treatment with cisplatin. However, overexpression or
      disruption of the FIT2 or FIT3 genes had little effect on the susceptibility of
      yeast to cisplatin. Although Fit2p and Fit3p do not appear to be directly
      involved in protecting against the toxic effects of cisplatin, the present
      results suggest the existence of an activation system of gene expression in
      response to cisplatin within yeast cells.

PMID- 16960439
TI  - Exercise capacity and pulmonary function in hospital workers recovered from
      severe acute respiratory syndrome.
AB  - BACKGROUND: Persistent impaired pulmonary function and functional capacity are
      common among survivors of severe acute respiratory syndrome (SARS). Whether the
      impairment was caused by SARS or pre-existing physical condition remains unclear.
      OBJECTIVE: This study investigated the influence of SARS on exercise capacity and
      pulmonary function of previously healthy medical staff. METHODS: Pulmonary
      function tests, including spirometry and carbon monoxide diffusing capacity
      (DLCO), as well as symptom-limited cardiopulmonary exercise testing (CPET) with
      an incremental protocol using an electronically braked cycle ergometer, were
      performed by 13 previously healthy hospital workers 14 months after SARS
      recovery. Other 14 age- and sex-matched healthy medical workers completed CPET
      simultaneously, and exercise capacities of these two groups were compared.
      RESULTS: Most values of spirometry performed were within normal range. Only one
      showed mildly restrictive abnormality with decreased forced expiratory volume in
      1 s (72.2% predicted) and forced vital capacity (68.1% predicted). Eight subjects
      had decreased DLCO levels (mean 79.37 +/- 7.73%), and low exercise capacity was
      noted in 9 subjects. Discordance in impairment of the measured DLCO and exercise
      capacity was revealed by comparison. Besides, there was no significant difference
      in results of CPET between subjects recovered from SARS and those never infected.
      CONCLUSIONS: Minor pulmonary function defects as well as decreased exercise
      capacity were detected in previously healthy medical staff after recovering from
      SARS. No significant correlation between exercise capacity and pulmonary function
      was found.

PMID- 16960438
TI  - Comparison of experimental lung injury from acute renal failure with injury due
      to sepsis.
AB  - BACKGROUND: Acute renal failure (ARF) and acute respiratory distress syndrome
      (ARDS) coexist frequently, and the mortality rate of this combination is very
      high. It is well established that cytokines and chemokines play a major role in
      the pathogenesis of ARDS. In addition, heat shock proteins (HSPs) have been shown
      to be protective against ARDS. OBJECTIVES: The purpose of this study was to
      investigate the pathophysiology of ARDS in two different conditions, sepsis and
      ARF. METHODS: We examined five different rat animal models including sham
      operated control, sepsis and three ARF models induced by renal
      ischemia/reperfusion injury, bilateral nephrectomy or bilateral ligation of renal
      pedicles. We analyzed pulmonary histology, pulmonary vascular permeability,
      cellular infiltration, and expression of cytokines, chemokines and HSPs. RESULTS:
      Like sepsis, the three forms of ARF led to ARDS, as manifested by increased
      pulmonary vascular permeability and histological changes consistent with ARDS. On
      the other hand, ARF and sepsis differed in that ARF was associated with markedly
      lower levels of pulmonary cellular infiltration. Furthermore, while pulmonary
      expression of tumor necrosis factor-alpha increased in sepsis, cytokine-induced
      neutrophil chemoattractant 2 increased in nephrectomized rats indicating that
      different inflammatory mediators were involved in the injury mechanism. Finally,
      pulmonary expression of multiple HSPs including HSP27-1, HSP70, HSP70-4, HSP70-8
      and HSP90 was significantly different between the two conditions. CONCLUSIONS: We
      conclude that the pathophysiology of ARDS following ARF is distinct from that in
      sepsis. ARF-induced ARDS is characterized by a low level of cellular
      infiltration, induction of cytokine-induced neutrophil chemoattractant 2, and a
      discrete expression profile of HSPs.

PMID- 16960440
TI  - Effects of salmeterol in patients with persistent asthma receiving inhaled
      corticosteroid plus theophylline.
AB  - BACKGROUND: Patients with severe asthma require multiple therapies to improve
      lung function and reduce symptoms. The use of long-acting inhaled beta(2)
      agonists plus theophylline in addition to high doses of inhaled corticosteroids
      (ICSs) for the treatment of severe asthma has not been extensively studied.
      OBJECTIVE: The purpose of this study was to investigate the efficacy and safety
      of salmeterol combined with high-dose ICSs plus theophylline in severe asthma.
      METHODS: We undertook a randomized, placebo-controlled, crossover study to
      compare the effect of a single dose of inhaled salmeterol (50 microg) or a
      placebo in patients with severe asthma whose conditions were not being adequately
      controlled by therapies with high-dose ICSs plus oral theophylline with or
      without leukotriene receptor antagonists. RESULTS: Twenty patients took part in
      the trial. Compared with the placebo, the inhalation of salmeterol significantly
      increased the FEV(1). Even in the 9 patients treated with high-dose ICSs plus
      theophylline plus a leukotriene receptor antagonist, the FEV(1) increased
      significantly more after salmeterol than after the placebo. CONCLUSION: Patients
      with severe asthma receiving high-dose ICSs plus theophylline may benefit from
      the addition of salmeterol.

PMID- 16960441
TI  - Hypertension induces oxidative stress but not macrophage infiltration in the
      kidney in the early stage of experimental diabetes mellitus.
AB  - BACKGROUND: The combination of diabetes and hypertension increases the incidence
      and severity of kidney disease in an additive manner. Inflammatory and oxidative
      stress mechanisms contribute to renal damage in both diabetes and hypertension.
      Therefore, we investigated whether renal macrophage infiltration and oxidative
      stress events are additive from the beginning in diabetic animals with coexisting
      hypertension. METHODS: Diabetes was induced in spontaneously hypertensive rats
      (SHRs) and their genetically normotensive control Wistar Kyoto (WKY) rats by
      streptozotocin injection at 12 weeks of age for 10 days, and the effects of
      hyperglycemia on renal macrophage infiltration and oxidative stress were
      evaluated. RESULTS: Blood pressure was higher in SHR than in WKY groups. Markers
      of oxidative stress-induced DNA and protein modification, 8-hydroxy- 2'
      deoxyguanosine (8-OHdG) and nitrotyrosine, respectively, and the antioxidant
      glutathione levels were found to be similar in WKY-control and WKY-diabetic
      groups. However, 8-OHdG was significantly elevated (p = 0.014), the nitrotyrosine
      level tended to be elevated (p = 0.068) and the glutathione level was
      significantly reduced (p = 0.034) in the SHR-diabetic group compared to the SHR
      control group. On the other hand, glomerular and tubulointerstitial macrophage
      infiltration was significantly higher in both WKY-diabetic and SHR-diabetic
      groups than the respective control groups. CONCLUSIONS: A short duration of
      diabetes mellitus induces renal oxidative stress in the presence of hypertension;
      however, renal macrophage infiltration becomes evident in early diabetes
      regardless of the presence or absence of hypertension. We conclude that the
      combination of diabetes and hypertension adversely affects oxidative stress in
      the kidney, but the combination has no additive effect on renal macrophage
      infiltration, at least in early diabetes.

PMID- 16960442
TI  - Heart fatty acid binding protein in the diagnosis of myocardial infarction: where
      do we stand today?
AB  - Heart fatty acid binding protein (hFABP) is a novel small cytosolic protein that
      is abundant in the heart. It is highly cardiac-specific (i.e. expressed primarily
      in cardiac tissue), but is also expressed at low concentrations in tissues
      outside the heart. After myocardial ischemic damage, hFABP can be detected in the
      blood as early as 1-3 h after onset of chest pain, with peak values reached at 6
      8 h and plasma levels returning to normal within 24-30 h. hFABP's clinical
      diagnostic value is very limited in the presence of renal failure and skeletal
      muscle diseases as it is completely renally eliminated. In these conditions, the
      diagnosis of acute myocardial infarction (AMI) may be overestimated. The
      combination of initial hFABP release after symptom onset, rapid kidney clearance
      from the circulation and high cardiac specificity suggests great potential for
      clinical use. Serial measurements of hFABP in the first 24 h after onset of
      symptoms in AMI patients can: (a) identify patients who are susceptible to
      reperfusion strategies, (b) detect perioperative AMIs, (c) distinguish patients
      who reperfuse their infarct-related artery from those who do not, as early as 30
      min after starting thrombolytic treatment, (d) detect re-infarction if it occurs
      within 10 h after symptom onset, and (e) permit an accurate estimation of
      myocardial infarct size providing important prognosis information.

PMID- 16960443
TI  - Non-invasive quantitation of myocardial fibrosis using combined tissue harmonic
      imaging and integrated backscatter analysis in dilated cardiomyopathy.
AB  - BACKGROUND: Echocardiographic modalities have challenged the myocardial tissue
      characterization, but this reliability has not reached to the clinical use. This
      study investigated whether combined tissue harmonic imaging (THI) and integrated
      backscatter analysis (IB) provide the reliable and quantitative information about
      myocardial fibrosis in idiopathic dilated cardiomyopathy (DCM) in comparison with
      myocardial biopsy findings. METHODS: We studied 56 patients with DCM. All
      patients underwent left ventricular endomyocardial biopsy and IB with fundamental
      imaging (FI) and THI. RESULTS: In patients with good echocardiographic image
      quality, excellent correlations between the percentage of area occupied by
      myocardial fibrosis (% fibrosis) and the mean of integrated backscatter during a
      cardiac cycle (m-IB) measured with FI or THI were seen, and the correlation was
      closer with THI compared with FI. While in patients with poor image quality the
      correlation between m-IB and % fibrosis was only modest with FI, but the
      correlation was excellent with THI. Four cut-off values of m-IB with THI obtained
      from receiver operating characteristic curve discriminated between % fibrosis of
      more and less than 25, 30, 35, and 40% with high sensitivity and specificity.
      Multivariate analysis revealed that m-IB with THI was an independent predictor
      for discrimination of the severity of myocardial fibrosis. CONCLUSION: Combined
      IB and THI are a clinically applicable method and may be an alternative to
      myocardial biopsy in evaluating quantitatively myocardial fibrosis in DCM.

PMID- 16960445
TI  - Impact of statin therapy on clinical outcomes in chronic heart failure patients
      according to beta-blocker use: results of CIBIS II.
AB  - BACKGROUND: HMG-CoA reductase inhibitors (statins) are widely prescribed in
      patients with established systolic chronic heart failure (CHF). However, there is
      considerable controversy regarding their benefit in this setting. We therefore
      conducted a post-hoc analysis of outcomes according to statin use within the
      Second Cardiac Insufficiency Bisoprolol Study of the beta-blocker, bisoprolol, in
      NYHA classes III-IV systolic CHF patients (left ventricular ejection fraction
      <35%), receiving background ACE inhibitor and diuretics. METHODS: Analysis of
      clinical outcomes was performed according to baseline use of statins and
      subsequent randomisation to placebo or bisoprolol. Cumulative incidence curves
      for clinical events were constructed using the Kaplan-Meier method and tested for
      significance by log-rank statistic. Multivariate analysis was performed using the
      Cox proportional hazards regression model. RESULTS: Two hundred and twenty-six of
      2,647 patients were receiving statins at baseline (8.5%). Patients were well
      matched in the 4 study groups at baseline for gender, weight, NYHA class and
      LVEF, however statin/bisoprolol patients were significantly younger (p < 0.05).
      Statin use at baseline was associated with a significant survival benefit
      compared with no statin use (p < 0.005, hazard ratio [HR] = 0.60, 95% confidence
      interval [CI] = 0.39-0.94). This benefit remained after adjusting for other
      significant predictors of survival (p < 0.05, HR = 0.60, 95%CI = 0.39-0.94). A
      significant interaction effect was noted with bisoprolol, survival being greatest
      in the statin/bisoprolol group (p < 0.001, HR = 0.14, 95% CI = 0.03-0.60).
      Survival was 98.3% in the statin/bisoprolol group, 82.1% in the statin/placebo
      group, 87.2% in the no statin/bisoprolol group and 82.8% in the no statin/placebo
      group. The statin/bisoprolol group was also associated with fewer cardiovascular
      (p < 0.005) and sudden deaths (p < 0.0005) compared with other groups.
      CONCLUSIONS: Despite the post-hoc, non-randomised nature of this analysis, these
      observations suggest that statin use appears to be beneficial in CHF.
      Furthermore, there appears to be a favourable interaction between statins and
      beta-blockade within the Second Cardiac Insufficiency Bisoprolol Study cohort.
      Prospective studies of statins are required to definitively address the role of
      these agents in established CHF.

PMID- 16960444
TI  - The effect of high extracellular potassium on IKr inhibition by anti-arrhythmic
      agents.
AB  - BACKGROUND: Hyperkalemia is a potentially life-threatening disorder frequently
      occurring in hospitalized patients. The ischemic myocardium releases potassium
      into the extracellular space which can cause regional hyperkalemia. These changes
      may modify the effects of anti-arrhythmic drugs acting on the rapid component of
      the delayed rectifier potassium current (IKr). We evaluated the influence of
      increased extracellular potassium concentration [K(+)](e) on IKr inhibition by
      amiodarone, azimilide, dofetilide, quinidine and sotalol. METHODS AND RESULTS:
      Experiments were performed at room temperature. IKr current was studied by using
      HERG gene expressed in Xenopus oocytes as a model of cardiac IKr. Two-electrode
      voltage clamp technique was employed. The recording bath solutions contained
      either 5 or 10 mmol/l KCl. Amiodarone, azimilide, dofetilide, quinidine and
      sotalol all produced a dose-dependent inhibition of HERG current. At 5 mmol/l
      [K(+)](e), the IC(50) was 37.0 +/- 12.5 microM for amiodarone, 5.8 +/- 0.4 microM
      for azimilide, 1.5 +/- 0. 2 microM for dofetilide, 9.1 +/- 1.5 microM for
      quinidine, and 5.1 +/- 0.8 mM for sotalol. Raising the extracellular potassium to
      10 mmol/l, HERG block by azimilide, dofetilide, quinidine and sotalol was
      significantly decreased, while the block by amiodarone was unchanged. The
      differences in the percentage current block produced by 3 microM drugs at 5 and
      10 mmol/l [K(+)](e) were: -0.9% for amiodarone, 13.8% for quinidine, 20.5% for
      azimilide, and 16.2% for dofetilide. The differences in percentage block between
      5 and 10 mmol/l [K(+)](e) by sotalol 10 and 30 mM were 7.1 and 5.6%. At 10 mmol/l
      [K(+)](e), the IC(50) was increased for azimilide, dofetilide, quinidine and
      sotalol but not for amiodarone; the IC(50) was 24.7 +/- 7.4 microM for
      amiodarone, 29.3 +/- 3.9 microM for azimilide, 2.7 +/- 0.2 microM for dofetilide,
      27.6 +/- 4.0 microM for quinidine, and 7.2 +/- 1.7 mM for sotalol. CONCLUSION:
      Inhibition of IKr by azimilide, quinidine, dofetilide and sotalol was diminished
      by increasing [K(+)](e), while the inhibition by amiodarone was unchanged at
      normal and high [K(+)](e). The differential effects of azimilide, dofetilide,
      quinidine and sotalol at normal and high [K(+)](e) could be pro-arrhythmic by
      favoring re-entry arrhythmias. These results further support the unique
      electrophysiological effect of amiodarone.

PMID- 16960446
TI  - The role of 123I-metaiodobenzylguanidine myocardial scintigraphy in the diagnosis
      of Lewy body disease in patients with dementia in a memory clinic.
AB  - Reduction in cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake is a
      characteristic feature of Parkinson's disease (PD) and dementia with Lewy bodies
      (DLB), and is useful in distinguishing them from other neurodegenerative
      disorders. The aim of this study was to investigate the role of this method of
      scintigraphy in the differential diagnosis of dementia in our Memory Clinic. We
      performed MIBG scintigraphy in patients with dementia referred to the Memory
      Clinic and compared the heart-to-mediastinum (H/M) ratio of MIBG uptake. Thirty
      out of 32 patients with DLB and all 9 PD with dementia patients had reduced H/M
      ratios, whereas 37 out of 40 patients with Alzheimer's disease had normal H/M
      ratios. Most patients with vascular dementia, frontotemporal dementia, and other
      dementias had normal H/M ratios. The overall sensitivity to positively identify
      patients with Lewy body disease (including DLB and PD with dementia) was 95%, and
      the specificity to distinguish them from patients with other types of dementias
      was 87%. MIBG scintigraphy showed a high sensitivity for the detection of Lewy
      body disease, and also a high specificity for discrimination from other types of
      dementia. The scintigraphy may provide a valuable and adjunctive method in the
      diagnosis of Lewy body disease and a differential diagnostic tool for patients
      with dementias.

PMID- 16960447
TI  - Validation of the Addenbrooke's cognitive examination for detecting early
      Alzheimer's disease and mild vascular dementia in a German population.
AB  - We assessed the diagnostic accuracy of the German version of the Addenbrooke's
      Cognitive Examination (ACE) in identifying early Alzheimer's disease (AD) and
      mild vascular dementia (VaD) in comparison with the conventional Mini-Mental
      State Examination (MMSE). The study refers to 50 patients with mild dementia of
      AD, 26 patients with mild dementia of vascular etiology and to 54 cognitively
      normal subjects. The ACE and MMSE were validated against an expert diagnosis
      based on a comprehensive diagnostic workup. Statistical analysis was performed
      using the receiver operator characteristics method. The optimal cut-off score for
      the ACE for detecting dementia in patients with early AD was 85/86, which had a
      sensitivity of 93% and a specificity of 86%. The optimal cut-off for the ACE for
      the identification of dementia in patients with mild VaD was also 85/86 and it
      had a sensitivity of 93% and a specificity of 100%. The kappa values imply a
      substantial agreement between the diagnoses made by the ACE and the MMSE. The
      German version of the ACE is a short and practical but accurate test battery for
      the identification of AD and VaD, assessing a broad range of cognitive functions
      and providing a wide profile of cognitive functions/dysfunctions.

PMID- 16960448
TI  - Statins of different brain penetrability differentially affect CSF PLTP activity.
AB  - BACKGROUND/AIMS: Phospholipid transfer protein (PLTP) and apolipoprotein E (apoE)
      are key proteins involved in lipoprotein metabolism in the peripheral circulation
      and in the brain. Several epidemiological studies suggested that use of 3
      hydroxyl-3-methylglutaryl-coenzyme A reductase inhibitors (statins) reduces risk
      of Alzheimer's disease (AD). However, the effects of statins of differing blood
      brain barrier (BBB) penetrability on brain-derived molecules in cognitively
      normal individuals are largely unknown. METHODS: To assess the effect of statins
      on these indices as a function of BBB penetration, cerebrospinal fluid (CSF) and
      plasma PLTP activity and apoE concentration were measured in cognitively intact,
      modestly hypercholesterolemic adults randomly allocated to treatment with either
      pravastatin, which does not penetrate BBB (80 mg/day, n = 13), or simvastatin,
      which penetrates BBB (40 mg/day, n = 10). RESULTS: Simvastatin significantly
      increased CSF PLTP activity (p = 0.005). In contrast, pravastatin had no such
      effect. In the pravastatin-treated group, CSF apoE concentration decreased
      significantly (p = 0.026), while the simvastatin-treated group showed a tendency
      towards lower CSF apoE levels, with CSF apoE concentration lowered in 8 of 10
      subjects. CONCLUSION: Our data indicate that statins differentially affect two
      key lipid transfer proteins in the brain, and that effect on PLTP activity
      depends on statin BBB penetrability.

PMID- 16960449
TI  - Intron 2 (T/C) CYP46 polymorphism is associated with Alzheimer's disease in
      Chinese patients.
AB  - BACKGROUND: Cholesterol metabolism has been implicated in the pathophysiology of
      Alzheimer's disease (AD), and cholesterol-related genes are plausible candidate
      genes for AD. Genetic association of CYP46A1 polymorphisms with AD had been under
      extensive investigations; however, observations on intron 2 T-->C (rs754203)
      generated inconclusive results. OBJECTIVE: To analyse an independent data set in
      a Chinese population to see whether the polymorphic site rs754203 of the CYP46A1
      gene is associated with AD. METHODS: We analysed 130 sporadic AD patients and 110
      healthy controls of the Southern Chinese origin. RESULTS: An association between
      the genotype frequency and AD was suggested in the general population (p = 0.047,
      odds ratio, OR = 1. 61, 95% confidence interval, CI = 0.96-2.70), while the
      association was most significant in the apolipoprotein E (ApoE) epsilon4-negative
      group (p = 0.004, OR = 2.54, 95% CI =1.31-4.95). Linkage disequilibrium block
      prediction results also favoured this association. Consistent with previous
      reports, intron 3 C-->T (rs4900442) polymorphism did not show any evidence of
      association; in our data set ApoEepsilon4 was confirmed to be a genetic risk
      factor for AD (p = 0.0016, OR = 2.76, 95% CI = 1.50-5.11).

PMID- 16960450
TI  - Is the ipsilateral cortex surrounding the lesion or the non-injured contralateral
      cortex important for motor recovery in rats with photochemically induced cortical
      lesions?
AB  - PRIMARY OBJECTIVE: To determine whether the ipsilateral cortex surrounding the
      lesion or the non-injured contralateral cortex is important for motor recovery
      after brain damage in the photochemically initiated thrombosis (PIT) model.
      RESEARCH DESIGN: We induced PIT in the sensorimotor cortex in rats and examined
      the recovery of motor function using the beam-walking test. METHODS AND
      PROCEDURES: In 24 rats, the right sensorimotor cortex was lesioned after 2 days
      of training for the beam-walking test (group 1). After 10 days, PIT was induced
      in the left sensorimotor cortex. Eight additional rats (group 2) received 2 days
      training in beam walking, then underwent the beam-walking test to evaluate
      function. After 10 days of testing, the left sensorimotor cortex was lesioned and
      recovery was monitored by the beam-walking test for 8 days. MAIN OUTCOMES AND
      RESULTS: In group 1 animals, left hindlimb function caused by a right
      sensorimotor cortex lesion recovered within 10 days after the operation. Right
      hindlimb function caused by the left-side lesion recovered within 6 days. In
      group 2, right hindlimb function caused by induction of the left-side lesion
      after a total of 12 days of beam-walking training and testing recovered within 6
      days as with the double PIT model. The training effect may be relevant to
      reorganization and neuromodulation. Motor recovery patterns did not indicate
      whether motor recovery was dependent on the ipsilateral cortex surrounding the
      lesion or the cortex of the contralateral side. CONCLUSION: The results emphasize
      the need for selection of appropriate programs tailored to the area of cortical
      damage in order to enhance motor functional recovery in this model.

PMID- 16960451
TI  - Efficacy and safety of simultaneous bilateral pallidotomy in advanced Parkinson's
      disease.
AB  - BACKGROUND: Although unilateral pallidotomy is generally considered a safe and
      effective neurosurgical treatment for advanced Parkinson's disease (PD),
      controversies concerning efficacy and adverse effects of bilateral posteroventral
      pallidotomy (PVP) exist and need to be resolved. METHODS: We studied 8 patients
      with advanced PD who underwent simultaneous bilateral PVP. The patients were
      assessed preoperatively, immediately after surgery, and 6 and 12 months later.
      RESULTS: Dyskinesia was almost entirely abolished immediately after surgery, as
      well as being significantly lower 1 year later (p < 0.05). The 'off' medication
      score of the Unified Parkinson's Disease Rating Scale motor part (UPDRS III) was
      significantly improved after surgery (p < 0.05) but increased gradually after 6
      months. The off medication score of activities of daily living tended to improve
      immediately after surgery, but it returned to preoperative levels at 12 months.
      There were no major complications of surgery. CONCLUSIONS: Simultaneous bilateral
      PVP may be a safe and highly effective method of reducing levodopa-induced
      dyskinesia. Our results suggest that simultaneous bilateral PVP may be a
      reasonable therapeutic option for advanced PD with severe levodopa-induced
      dyskinesia.

PMID- 16960452
TI  - CYP2C19 polymorphism and risk for essential tremor.
AB  - Many patients with essential tremor (ET) develop acute adverse effects to
      primidone. We investigated the association between CYP2C19 polymorphism (possibly
      related to primidone metabolism) and the risk for developing essential ET and
      acute adverse effects to primidone. Leukocytary DNA from 200 ET patients and 300
      healthy controls was studied for the genotype CYP2C19 and the occurrence of
      CYP2C19 allelic variants by using allele-specific PCR amplification and Sma I and
      BamH I RFLP analyses. The frequencies of the genotype CYP2C19*1/CYP2C19*2 and of
      the allelic variant CYP2C19*2 were significantly higher in ET patients than in
      controls. The mean age at onset of ET did not differ significantly between
      patients with genotypes CYP2C19*1/CYP2C19*2andCYP2C19*1/CYP2C19*1. The
      frequencies of the genotype CYP2C19*1/CYP2C19*2 and the allelic variant CYP2C19*2
      were similar in ET patients who developed acute adverse effects to primidone, in
      those who tolerated primidone and in controls; the frequencies were also similar
      in patients with head, voice, tongue and chin tremor compared with controls.
      These results suggest that heterozygosis CYP2C19*1/CYP2C19*2 is associated with
      the risk for ET, but not with the age at onset of ET, the presentation of acute
      side effects of primidone, or the existence of head, voice, tongue or chin
      tremor.

PMID- 16960453
TI  - Bronchial involvement in the cramp-fasciculation syndrome.
AB  - BACKGROUND/AIMS: Cramp-fasciculation syndrome (CFS) is an acquired, chronic,
      usually benign and rather heterogeneous condition with isolated fasciculations
      and muscle cramps generally induced by physical exercise. They commonly involve
      calf and quadriceps muscles. The pathophysiology of CFS is related to peripheral
      nerve hyperexcitability, most often located at the motor nerve terminal or
      intramuscular arborization. METHODS: A 21-year-old man presented with a
      progressive syndrome of bronchospasm, cramps and muscle twitches related to
      physical exercise. Spirography showed bronchial hyperresponsiveness, so he
      received inhaled corticosteroids and beta2-agonists that improved respiratory
      symptoms. Electrodiagnostic studies were consistent with CFS. Gabapentin was then
      introduced. RESULTS: Both respiratory and muscle symptoms improved. A new
      spirogram after all inhaled medication had been discontinued was normal.
      CONCLUSION: This picture suggests a concomitant involvement of the peripheral
      motor nerves of both skeletal and airway autonomic smooth muscle, a presentation
      not previously reported in CFS.

PMID- 16960454
TI  - Bilateral effects of unilateral subthalamic nucleus deep brain stimulation in
      advanced Parkinson's disease.
AB  - To investigate the bilateral effects of unilateral subthalamic nucleus deep brain
      stimulation (STN-DBS), we prospectively studied 9 consecutive advanced
      Parkinson's disease (PD) patients (2 men and 7 women) who underwent unilateral
      STN-DBS. Patients were evaluated preoperatively and at 3 and 6 months
      postoperatively with and without dopaminergic medications ('on' and 'off'
      medication, respectively). Postoperatively, patients were assessed with and
      without stimulation. We found that, when compared with baseline, the 'off'
      medication scores of the Unified Parkinson's Disease Rating Scale motor part
      (UPDRS III) and activities of daily living (UPDRS II) were improved by 37% (p =
      0.028) and 50% (p = 0.046) at 6 months after surgery, respectively. Stimulation
      while 'off' medication improved the total UPDRS score by 42% (p = 0.028) at 6
      months. At 6 months after surgery, the subscore of UPDRS III of body parts
      contralateral to the DBS implantation had improved by 48% (p = 0.028), and the
      ipsilateral subscore of UPDRS III and the axial subscore of UPDRS III had
      improved by 20% (p = 0.027) and 39% (p = 0.028), respectively. Daily dosage of
      levodopa was reduced by 15% at 6 months. No patient exhibited permanent side
      effects. These findings indicate that unilateral STN-DBS may be a reasonable
      surgical procedure for selected PD patients who have markedly asymmetric
      parkinsonism.

PMID- 16960455
TI  - Transient global amnesia following vertebral artery angioplasty and stenting.

PMID- 16960456
TI  - The craniospinal venous system.
AB  - The valveless craniospinal venous system consists of veins and plexuses that
      communicate freely and whose flow is bidirectional. It comprises (1) the
      intracranial-cortical veins, dural sinuses, cavernous sinuses and ophthalmic
      veins, and (2) the vertebral venous plexuses, which freely anastomose with the
      intracranial venous system. The vertebral venous plexuses anastamose with the
      sacral, pelvic and prostatic venous plexus. It is clinically important since it
      provides a route for the spread of tumours, infection or emboli. This route may
      go unrecognised.

PMID- 16960457
TI  - Self-care dimensions of complementary and alternative medicine use among older
      adults.
AB  - BACKGROUND: There is a lack of understanding about the patterns and rates of CAM
      use among older adults owing to a lack of research on specific types of CAM.
      OBJECTIVES: This study examines several dimensions of self-care deemed to be
      associated with CAM. Unmet health care needs, self-care attitudes, and
      spirituality are interpreted as health belief structures underlying CAM. METHODS:
      Logistic regression analysis was used to examine use of three groups of
      practitioner-based CAM: (a) chiropractic; (b) massage, and (c) acupuncture,
      homeopathy and/or naturopathy use. We analyze a subsample of 4,401 older adults
      drawn from the 1996/1997 and 1998/1999 waves of the Canadian National Population
      Health Survey. RESULTS: The logistic regression analyses indicate that self-care
      attitude and spirituality represent important predictors of practitioner-based
      CAM use. The associations for unmet health care needs were not supported. The
      strongest factors associated with CAM use were the illness context variables,
      which suggest that measures of need are key factors in leading individuals to
      seek other forms of health care. DISCUSSION: Practitioner-based CAM use among
      older adults is influenced by self-care attitude and spirituality, in addition to
      health status, but to varying degrees depending on the type of CAM. Support of
      these self-care facets suggests that there is a desire on the part of consumers
      to exercise choice and to participate in health care decisions when considering
      CAM.

PMID- 16960458
TI  - Plasma concentrations of tumor necrosis factor alpha may predict the outcome of
      patients with acute renal failure.
AB  - BACKGROUND/AIMS: Elevated plasma tumor necrosis factor-alpha (TNFalpha)
      concentration is frequently found in patients with chronic renal failure on
      hemodialysis (HD) and correlates with their mortality. The present study aimed to
      analyze the relationship between plasma TNFalpha concentrations and survival of
      patients with nonseptic acute renal failure (ARF). METHODS: Twenty-seven patients
      with ARF and 27 HD patients were examined. In ARF the patients' plasma TNFalpha
      concentrations were assessed 3 times: before the first HD session (phase I), 5
      days later at the anuric/oliguric phase (phase II), and at the polyuric phase at
      discharge of the patients from the hospital (phase III). In 17 ARF patients
      kidney function recovered and 10 patients died in phase I. RESULTS: In ARF
      patients plasma TNFalpha concentration was markedly higher [70 pg/ml (37-275)]
      than reference values (<5 pg/ml) but significantly lower than in HD patients [216
      pg/ml (18-350)]. Moreover, also plasma TNFalpha levels at the polyuric phase
      remained elevated. An initial plasma TNFalpha concentration in ARF patients lower
      than 70 pg/ml predicted the beneficial outcome with a sensitivity of 64.7% and a
      specificity of 70.0%. CONCLUSIONS: (1) Plasma TNFalpha concentration may predict
      the outcome in patients with ARF. (2) Plasma TNFalpha concentration remained
      elevated at the polyuric phase in ARF despite a marked improvement of excretory
      kidney function.

PMID- 16960459
TI  - Blood pressure, renal function, and proteinuria in children with unilateral renal
      agenesis.
AB  - BACKGROUND/AIM: Unilateral renal agenesis (URA) is a model for a reduced nephron
      number that is believed to be a risk factor for blood pressure (BP) elevation and
      reduced renal function. The aim of the study was to investigate BP and renal
      function in children with URA. METHODS: Data on children with URA from two
      pediatric nephrology centers were firstly retrospectively reviewed (renal
      ultrasound and scintigraphy, clinical BP, creatinine clearance, urinalysis).
      Children with normal renal ultrasound and scintigraphy were thereafter
      investigated using ambulatory BP monitoring. RESULTS: Twenty-nine children with
      URA were investigated--14 children with an abnormal kidney (mostly scarring) and
      15 children with healthy kidneys. Hypertension was diagnosed on the basis of
      clinical BP in 57% of the children with abnormal kidneys and on the basis of
      ambulatory BP monitoring in 1 child (7%) with healthy kidneys. The mean
      ambulatory BP in children with normal kidneys was not significantly different
      from that in controls. Forty-three percent of the children with abnormal kidneys
      had a reduced renal function, but none of children with normal kidneys.
      CONCLUSIONS: Children with abnormalities of a solitary kidney have often
      hypertension, proteinuria, or a reduced renal function. In contrast, children
      with healthy solitary kidneys have BP and renal function similar to those of
      healthy children.

PMID- 16960460
TI  - Antiproteinuric effect of losartan in non-diabetic renal disease is not dependent
      on ACE insertion/deletion polymorphism.
AB  - BACKGROUND: The antiproteinuric effect of angiotensin-converting enzyme (ACE)
      inhibitors appears to vary depending on the ACE insertion (I)/deletion (D)
      genotype in non-diabetic nephropathy. This interaction may be overcome by using
      an angiotensin II receptor blocker. We evaluated the short-term antiproteinuric
      effect of losartan according to the ACE I/D genotype in patients with non
      diabetic proteinuric renal diseases. METHODS: Ninety-nine (II/ID/DD: 36/52/11)
      non-diabetic patients with overt proteinuria were enrolled. The patients received
      losartan 50 mg daily followed by 100 mg in two treatment periods each lasting 12
      weeks. Clinical parameters including proteinuria were measured at baseline and at
      the end of each period. RESULTS: At baseline each genotype (II/ID/DD) had
      comparable mean arterial blood pressure (mean +/- SD) 103.2 +/- 11.1/102.7 +/-
      10.6/104.1 +/- 15.3; proteinuria (geometric mean, 95% CI, mg/day) 1,839 (1,518
      2,227)/1,998 (1,683-2,372)/1,613 (1,072-2,427), and creatinine clearance
      (ml/min/1.73 m(2)) 65.7 +/- 28.4/63.2 +/- 27.8/68.8 +/- 25.3, respectively. Both
      doses of losartan significantly lowered blood pressure and proteinuria (p < 0.05
      vs. baseline), and losartan 100 mg was more effective than 50 mg in reducing
      proteinuria (52.5 +/- 29.0 vs. 40.5 +/- 30.8%, respectively, p = 0.001). No
      differences in the antiproteinuric effect of losartan was observed among the ACE
      I/D genotype. Losartan 100 mg demonstrated a comparable degree of mean arterial
      pressure (mean +/- SD, %) (II/ID/DD, 13.3 +/- 7.6/10.8 +/- 9.8/13.0 +/- 11.6,
      respectively, p = NS) and proteinuria reduction (mean, 95% CI) among the three
      genotypes (51.4% (40.3-62.5%)/53.4% (45.5-61.4%)/51.4% (40.0-63.8%),
      respectively, p = NS). CONCLUSION: Our data suggest that losartan provides a
      similar short-term antiproteinuric response for all three genotypes of ACE I/D
      genotype in non-diabetic proteinuric chronic renal disease.

PMID- 16960461
TI  - Different effects of growth factors on human renal early distal tubular cells in
      vitro.
AB  - BACKGROUND: In the kidney, recovery from tubular damage requires regenerative
      mechanisms leading to re-epithelialization of the injured tubules. Current
      evidence supports the para- or autocrine role of growth factors in repair and
      regeneration of ischemic or nephrotoxic experimental acute renal failure.
      METHODS: We evaluated the effects of EGF, HGF, IGF-1, and bFGF on human renal
      thick ascending limb and distal convoluted cells (TALDC) in vitro. TALDC were
      isolated by immunomagnetic separation and cultured. Signal transduction of the
      growth factors was evaluated by Western blot of ERK1/2 MAP-K phosphorylation.
      Cell proliferation was measured by MTT assay and a fluorometric assay. RESULTS: A
      significant, dose- and time-dependent phosphorylation of ERK1/2 could be detected
      exclusively after stimulation with EGF. No other growth factor induced a
      significant MAPK phosphorylation. In the same manner, proliferation assays showed
      a significant growth-promoting effect of EGF. Neither HGF, nor IGF-1 or bFGF
      showed a stimulative effect on TALDC proliferation. CONCLUSION: The present study
      highlights the effects of growth factors on cultured TALDC and supports the
      hypothesis that in vivo EGF plays a para- or autocrine role during renal repair
      mechanisms.

PMID- 16960462
TI  - The alteration of QT dispersion in hemodialysis subjects.
AB  - OBJECTIVE: We attempted to observe the alterations in QTd and QTcd in chronic
      renal failure (CRF) patients before and after hemodialysis (HD) to determine the
      relevant determinants of QTc duration in HD. METHODS: The HD was carried out 2 or
      3 times/week in a standard setting for 4-4.5 h. No drug therapy was applied
      during HD, except for isotonic NaCl infusions and sodium heparin. Maintenance
      drug therapy, including digitalis, antihypertensive, anti-anginal, and beta
      blocking agents, was not changed. In the study, we investigated the alterations
      in QTd and QTcd in 68 CRF patients before and after HD with 12-lead ECG. Plasma
      Na(+), K(+), ionized Ca, creatinine, urea nitrogen, and hemoglobin were also
      controlled before and after HD. RESULTS: In our study QTd and QTcd significantly
      increased at the end of HD (p < 0.01). Plasma Na(+) and K(+) decreased, and
      ionized Ca increased after HD (p < 0.05, 0.01). Plasma Na(+), K(+), ionized Ca
      levels, ultrafiltration volume and myocardial ischemia appear to be the main
      determinants of QTc duration in HD, not hypertension, gender, patient age, or
      duration of chronic HD. CONCLUSION: Changes in plasma Na(+), K(+) and ionized Ca,
      the ultrafiltration volume and presence of ischemic heart disease in HD have
      significant effects on QTcd. ECG data demonstrate that the risk of arrhythmia
      could be higher with decreased plasma Na(+) and K(+), increased ionized Ca, the
      presence of ischemic heart disease and an increased ultrafiltration rate during
      HD. These results might provide some valuable references for proper HD programs.

PMID- 16960463
TI  - Evidence for the presence of histamine uptake into the synaptosomes of rat brain.
AB  - Histamine has many physiological roles in the brain and periphery. Neuronal
      histamine is metabolized almost exclusively by histamine N-methyltransferase.
      Although several neurotransmitter systems such as dopamine and 5
      hydroxytryptamine have their specific reuptake system in their neurons and glial
      cells, a specific histamine reuptake system into the corresponding nerve
      terminals or glial cells has not yet been clearly elucidated. We characterized
      the uptake of histamine into the P2 fractions of rat brain homogenized in 0.32
      mol/l sucrose using in vitro uptake techniques. [3H]histamine uptake increased
      with the increment of added protein amount and elapsed time. [3H]histamine uptake
      was also temperature-dependent. The uptake of [3H]histamine into the P2 fractions
      occurs by two saturable processes, a high-affinity and a low-affinity,
      characterized by K(m) values of 0.16 and 1.2 micromol/l, respectively. Na(+), Cl(
      ) and HCO(3)(-) ions were essential for the uptake of histamine in P2 fractions.
      [3H]histamine uptake was inhibited in the presence of several tricyclic
      antidepressants. In accordance with this, the endogenous release of histamine
      from brain slices evoked by 100 mmol/l K(+) was augmented in the presence of 20
      micromol/l imipramine. These results further support the existence of a specific
      histamine uptake system in the brain, although the precise molecular entities
      have not been identified until now.

PMID- 16960464
TI  - Approaching delusional misidentification syndromes as a disorder of the sense of
      uniqueness.
AB  - Co-occurrence of the different types of delusional misidentification syndromes
      (DMS) implies a common pathogenetic substrate. Until now, theoretical
      explanations have strained to produce a collective approach, but have been
      trammeled by the initial definition of the syndromes (Capgras/Fregoli) that
      originated from the attribution of causal significance to the element of
      familiarity towards the misidentified object. In this article, we present two
      cases illustrating the co-occurrence of the syndromes and we attempt to propose a
      new approach to DMS. We hypothesize that a common potential pathogenetic factor
      underlying DMS could be a disorder of the sense of uniqueness. The ability to
      attribute uniqueness to the self and to surrounding people, objects, or places is
      a principal property of the adaptable mind that acts as a matrix for the
      identification process. We propose that although the term 'identity' encompasses
      the concept of uniqueness, this must be accomplished somewhere in a model of
      semantic processing of identity. Our approach is questioning the current view
      that this sequential stage is the PIN stage in the functional model of face
      recognition by Bruce and Young, and we attempt to see the disordered sense of
      uniqueness within the evolved form of the model of face recognition and
      delusional misidentification introduced by Ellis and Lewis. We propose that such
      a disturbance could result in an unstable identification process, vulnerable to
      discrepancies in perceptual, emotional, or memory input caused by psychotic or
      organic mental states, thus resulting in a breakdown of the identification
      process that inevitably leads to a delusion of denial of identity, or to a
      delusion of 'doubles'.

PMID- 16960465
TI  - Diagnostic agreement of schizophrenia spectrum disorders among chronic patients
      with functional psychoses.
AB  - BACKGROUND: To investigate whether diagnostic agreement across different
      diagnostic systems improves in a sample of chronic patients suffering from
      functional psychosis compared to first-admitted patients. SAMPLING AND METHODS:
      Among 353 patients with a history of functional psychosis, a subset of 100
      individuals (35 women and 65 men) were randomly sampled and assessed using the
      Operational Criteria Checklist for Psychotic Illness and Affective Illness
      (OPCRIT). Based on the OPCRIT diagnoses the subjects suffering from schizophrenia
      and schizophrenia spectrum disorders according to seven diagnostic systems were
      identified. Diagnostic agreement was assessed using unweighted kappa-statistics
      and pairwise concordance rates (CR). RESULTS: High diagnostic agreement of
      schizophrenia was observed across the ICD-10 and DSM systems (CR >0.70, kappa
      >0.70), which all had a significantly lower concordance to the St. Louis Criteria
      (SLC), research diagnostic criteria and Schneider's first rank symptoms (FRS)
      (0.32< CR <0.66; -0.10< kappa <0.51). Agreement on schizophrenia across all
      systems was observed for one fourth of the subjects. Elimination of the
      diagnostic impact of 'co-occurrence of psychotic and affective symptoms' excluded
      FRS standalone individuals from the sample, increased overall homogeneity and
      resulted in a dichotomized sample according to SLC (46 positive vs. 47 negative).
      SLC status could be predicted in 78% of cases by four items relating to family
      history and psychosocial function previous to the onset of illness. Similarly
      high pairwise CR were observed for schizophrenia spectrum disorders across all
      diagnostic systems. CONCLUSIONS: This study demonstrates that diagnostic
      agreement is higher among chronic patients than that observed in subjects with a
      recent onset of psychosis, although considerable discordance is also observed in
      this chronic sample. However, the discordance among chronic patients with
      functional psychosis largely derives from the different emphasis that diagnostic
      systems place on co-occurrence of psychotic and affective symptoms. This may have
      serious epistemological consequences, thus underlining the conventional nature of
      the present schizophrenia diagnoses and the need for biologically founded
      diagnostic criteria.

PMID- 16960466
TI  - Interpretation of ambiguous idiomatic statements in schizophrenic and depressive
      patients. Evidence for common and differential cognitive patterns.
AB  - BACKGROUND: This study is concerned with the comprehension of ambiguous idiomatic
      statements in schizophrenic and depressive patients. AIMS: Using a multiple
      choice procedure, we simultaneously tested the presence of concrete and literal
      elements in the understanding of idiomatic statements. METHOD: Fourteen
      schizophrenic and 10 patients undergoing a major depressive episode as well as 14
      control subjects completed a questionnaire with 10 idiomatic expressions with two
      possible interpretations (figurative and literal) of equivalent prominence. The
      participants had to choose one word linked with the different interpretations of
      these idioms (figurative, literal, concrete or inappropriate meaning). RESULTS:
      The main results show that, in all the subjects, the contextual characteristics
      of the task induced a bias in favor of figurative interpretations despite the
      equivalent prominence of the literal interpretations of the idioms. The selection
      of responses relating to the concrete meaning of a single word in the idiom
      constituted a response mode common to both the schizophrenic and depressed
      patients. Despite the contextual constraints of the task, the schizophrenics
      opted for the literal responses more often than the other participants. The
      descriptive analysis argues in favor of a cognitive and clinical heterogeneity of
      schizophrenic patients. CONCLUSION: Results support the idea that literality and
      concreteness in idiomatic interpretation are possibly due to distinct cognitive
      impairments, though only some are specific to schizophrenic patients.

PMID- 16960467
TI  - Characterization of patients with schizophrenia and related psychoses: evaluation
      of different diagnostic procedures.
AB  - BACKGROUND: We aimed at estimating the value of structured interviews, medical
      records and clinical diagnoses for assessing lifetime diagnosis of patients with
      schizophrenia. In addition, the validity of the Operational Criteria Checklist
      (OPCRIT) system was analysed. SAMPLING AND METHODS: Swedish patients (n = 73),
      diagnosed with schizophrenia and related disorders by their treating physician,
      were scrutinized. Independent research diagnoses according to the Diagnostic and
      Statistical Manual, ed. 3, revised (DSM-III-R) were obtained by (1) a structured
      interview; (2) the OPCRIT algorithm, based on record analysis only; (3) the
      OPCRIT algorithm, based on record and interview analysis, or (4) a separate
      traditional research diagnosis based on both record and interview analysis. In
      addition, clinical International Classification of Diseases (ICD) diagnoses,
      given by the treating physician, were obtained from the case notes. Concordance
      rates for the different psychosis diagnoses were calculated. RESULTS: Diagnoses
      based on interviews only showed poor to fair agreement with the other research
      diagnoses, but patients diagnosed with schizophrenia or schizophrenic psychoses
      (i.e. schizophrenia, schizophreniform or schizoaffective disorder) at the
      interview almost always also obtained a corresponding research diagnosis based on
      record or combined sources. Diagnoses based on records only showed a good to
      excellent agreement with diagnoses based on records and interviews. Clinical ICD
      diagnoses generally displayed poor agreement with the research diagnoses, but 94%
      of patients ever given a clinical ICD diagnosis of schizophrenic psychosis
      received a corresponding traditional research diagnosis. OPCRIT diagnoses and
      independently assigned research diagnoses, based on the same information,
      displayed excellent concordance. CONCLUSIONS: Structured interviews performed
      with Swedish long-term-treated psychosis patients during non-hospitalization are
      a poor source for the evaluation of psychosis diagnoses, but a good screening
      instrument for the detection of DSM-III-R schizophrenia. In the investigated
      population, medical records are a valuable source for diagnostic assessment of
      psychoses and may serve as a stand-alone procedure in this patient category.
      Swedish clinical ICD diagnoses have a high positive predictive power identifying
      DSM-III-R diagnoses of schizophrenic psychoses, indicating validity of register
      based research focusing on these diagnoses. The OPCRIT system is a valid tool for
      assessing DSM-III-R psychosis diagnoses. It should be emphasized that the present
      conclusions are based on the investigated Swedish psychosis population and cannot
      be generalized to populations composed of other patient groups or sampled in
      other settings, with other traditions regarding the use and availability of
      medical records.

PMID- 16960468
TI  - Comparison of dapoxetine versus paroxetine in patients with premature
      ejaculation: a double-blind, placebo-controlled, fixed-dose, randomized study.
AB  - PURPOSE: To compare the efficacy and safety of dapoxetine, paroxetine, and
      placebo for the oral pharmacotherapy of premature ejaculation. MATERIALS AND
      METHODS: Three hundred forty potent men with premature ejaculation were recruited
      to this study. Patients were randomly assigned to receive 60 mg dapoxetine (group
      1, n = 115), or 20 mg paroxetine (group 2, n = 113) or placebo (group 3, n = 112)
      orally daily during a 12-week period for each agent. The efficacy of the 3
      treatments was assessed every 2 weeks during treatment and at the end of study
      using responses to International Index of Erectile Function (IIEF), intravaginal
      ejaculatory latency time (IELT) evaluation, mean intercourse satisfaction domain,
      mean weekly coitus episodes and adverse drug effects. RESULTS: At the end of the
      12-week treatment with dapoxetine, paroxetine, and placebo, the mean IELT was
      increased from 38, 31 and 34 seconds to 179, 370 and 55 seconds, respectively (P
      = 0.01 in group 1 and P = 0.001 in group 2). Baseline mean intercourse
      satisfaction domain values of International Index of Erectile Function of 10, 11,
      and 11 reached 14, 17 and 12 at the end of the 12-week treatment in groups 1, 2,
      and 3 respectively (P = 0.03 in groups 1, 2). The mean weekly intercourse
      episodes increased from pretreatment values of 1.4, 1.3, and 1.3 to 2.2, 2.5 and
      1.4, for dapoxetine, paroxetine and placebo, respectively (P = 0.04 in groups 1,
      2). The incidence of adverse effects with dapoxetine and paroxetine was
      significantly higher (P = 0.04 in groups 1, 2) compared to that of placebo.
      CONCLUSIONS: Paroxetine appears to provide significantly better results in terms
      of IELT and intercourse satisfaction versus dapoxetine. Each treatment was well
      tolerated.

PMID- 16960469
TI  - Lamotrigine as an add-on treatment for depersonalization disorder: a
      retrospective study of 32 cases.
AB  - OBJECTIVES: Depersonalization disorder (DPD) is a chronic condition characterized
      by the persistent subjective experience of unreality and detachment from the
      self. To date, there is no known treatment. Lamotrigine as sole agent was not
      found to be effective in a previous small double-blind, randomized crossover
      trial. However, evidence from open trials suggests that it may be beneficial as
      an add-on medication with antidepressants. METHODS: We report here an extended
      series of 32 patients with DPD in whom lamotrigine was prescribed as an
      augmenting medication. Most of the patients were receiving selective serotonin
      reuptake inhibitors. RESULTS: Fifty-six percent (n = 18) of patients had a more
      than or equal to 30% reduction on the Cambridge Depersonalization Scale score at
      follow-up. Both maximum dose of lamotrigine used and before treatment Cambridge
      Depersonalization Scale scores showed positive correlations with the percentage
      of response. CONCLUSIONS: The results of this trial suggest that a significant
      number of patients with DPD may respond to lamotrigine when combined with
      antidepressant medication. The results are sufficiently positive to prompt a
      larger controlled evaluation of lamotrigine as "add-on" treatment in DPD.

PMID- 16960470
TI  - Is history of depression a contraindication to treatment with tetrabenazine?
AB  - OBJECTIVE: To determine whether a history of depression predisposes hyperkinetic
      patients treated with tetrabenazine (TBZ) to a recurrence or worsening of this
      symptom. METHODS: We retrospectively reviewed the charts of 518 patients treated
      with TBZ to determine the frequency of depression and other adverse events.
      Charts were screened for the preexistence, development, or exacerbation of
      depression during the course of treatment. RESULTS: The most common adverse
      events related to TBZ were somnolence (27.4%), depression (15.1%), parkinsonism
      (11.8%), and akathisia (8.9%); 78 patients (15.1%) experienced depression for the
      first time or an exacerbation of existing depression. Of those patients with no
      history of depression, 28 (11.4%) of 246 were newly diagnosed with depression.
      Patients with a documented history of depression experienced a significantly
      higher rate of worsening in 50 (18.4%) of 272 cases (P = 0.03). However, patients
      with a history of depression experienced more improvement of their hyperkinesia
      compared to those without a history of depression (P < 0.01). CONCLUSIONS:
      Depression, an adverse event of TBZ, is more likely to occur or worsen in
      patients with a preexisting history of depression.

PMID- 16960471
TI  - Levetiracetam in tardive dyskinesia.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of levetiracetam on
      tardive dyskinesia (TD), which is known to be a major limitation of chronic
      antipsychotic drug therapy, particularly with conventional antipsychotics.
      METHODS: Sixteen patients suffering from chronic psychosis with TD were enrolled
      consecutively. Levetiracetam was given in gradually increasing doses, starting
      with 125 twice a day until the best clinical benefit was achieved (mean dosage,
      2,290 mg; range, 1,000-3,000 mg). Tardive dyskinesia was assessed using the
      Abnormal Involuntary Movement Scale at baseline and after 1 month and 3 months of
      treatment with levetiracetam. RESULTS: Compared with baseline, there was a
      significant improvement in the Abnormal Involuntary Movement Scale score after 1
      month still present after 3 months (P < 0.001). All patients well tolerated
      levetiracetam, except one who dropped out of the trial after the first 2 weeks
      owing to excessive drowsiness. CONCLUSIONS: The results of this open-label
      observational study suggest that levetiracetam is a well-tolerated drug and
      effectively controls TD.

PMID- 16960472
TI  - Topiramate and triptans revert chronic migraine with medication overuse to
      episodic migraine.
AB  - OBJECTIVE: This is a randomized, double-blind versus placebo study aimed at
      evaluating the efficacy of topiramate (TPM) in reducing the number of days with
      headache and the amount of acute medication taken monthly in patients with
      chronic migraine with medication overuse. We also studied the efficacy of single
      triptans available in Italy in interrupting headache crises during preventive
      treatment. METHODS: The studied sample was made up of 50 subjects: 30 patients
      were randomized for treatment with TPM, 100 mg/d, and 20 for placebo. Subjects
      treated with TPM were further randomized to evaluate, in double-blind versus
      placebo, the efficacy of single triptans available in Italy. The double-blind
      phase consisted of a titration phase (4 weeks) and of a maintenance phase (8
      weeks). OUTCOME MEASURES: The reduction in the number of days with headache per
      28 days and the reduction in the amount of acute medication taken per 28 days
      throughout the clinical trial in the TPM group were compared with those of the
      placebo group; the number of patients who were pain-free at 2 hours after the
      triptan intake and the headache recurrence rate in the 22 hours after the pain
      free condition in the triptan group were compared with those of the placebo
      group. We also looked at tolerability profile. RESULTS: The group treated with
      TPM had a significant reduction in the number of days with headache (P < 0.0001
      vs placebo) and in the mean amount of acute medication taken (P < 0.0001 vs
      placebo); all triptans were superior to placebo; there were no significant
      differences between different triptans; the analgesic effect of triptans
      increased throughout the trial. CONCLUSIONS: Topiramate proved to be well
      tolerated and effective in reverting chronic migraine with medication overuse to
      episodic migraine.

PMID- 16960473
TI  - Challenging the serotonergic system in Parkinson disease patients: effects on
      cognition, mood, and motor performance.
AB  - BACKGROUND: Parkinson disease (PD) is a neuropsychiatric disease that is
      characterized by motor and neuropsychiatric symptoms. Multiple neurotransmitter
      systems, including the serotonergic system, are involved in the pathophysiology
      of this disease. The exact role of the serotonergic system in PD is still
      unclear. OBJECTIVE: To investigate the role of serotonin on specific aspects of
      cognition, mood, and motor performance in PD. METHODS: In a double-blind,
      randomized, placebo-controlled, crossover design, the effects of a nonspecific
      serotonergic challenge with citalopram, a selective serotonin reuptake inhibitor,
      and a 5-HT1a receptor-specific challenge with buspirone on the Visual Verbal
      Learning Task, Concept Shifting Task, Profile of Mood State Questionnaire, motor
      section of the Unified Parkinson Disease Rating Scale (section 3), Simple
      Reaction Time Task, and Finger Precuing Task were studied in 21 PD patients in
      early stages of their disease and 21 age-, sex-, and education-matched healthy
      volunteers. RESULTS: The serotonergic challenges resulted in similar effects for
      both groups. No changes of scores on the cognitive tasks (Visual Verbal Learning
      Task and Concept Shifting Task) were observed. Results of the Profile of Moods
      State Questionnaire indicated that, at baseline, PD patients scored less than
      controls on all 5 subscales. Motor performance (measured by reaction time) was
      negatively affected by the interventions. CONCLUSIONS: The effects of nonspecific
      and 5-HT1a receptor-specific challenging of the serotonergic neurotransmitter
      system had similar effects in both PD patients and healthy control subjects.
      These findings indicate that serotonergic function is not impaired in early PD
      and that serotonin, although involved in the pathophysiology of PD, does not seem
      to play a direct role in cognition, mood, and motor performance in PD patients,
      but may be involved in hypokinesia.

PMID- 16960474
TI  - Efficacy of mitoxantrone and intrathecal triamcinolone acetonide treatment in
      chronic progressive multiple sclerosis patients.
AB  - Treatment approaches are rare for chronic progressive patients with multiple
      sclerosis (MS). Objective was to evaluate the clinical benefit of repeated
      intrathecal application of the sustained release steroid triamcinolone acetonide
      or the administration of mitoxantrone (MIX) in 2 similar cohorts of chronic
      progressive patients with MS in an open-label fashion. Expanded Disability Status
      Scale scores significantly decreased after the first 6 intraspinal triamcinolone
      acetonide injections, which were performed every third day, and then remained
      stable. Walking distance significantly increased and did not reduce until the end
      of the 1-year-long trial period. Mitoxantrone treatment did not improve the
      Expanded Disability Status Scale score; however, no further significant
      deterioration appeared. Walking distance did not significantly decrease. Both
      treatment regimens were safe; the patients experienced nearly no adverse effects.
      Triamcinolone acetonide application provided a clinical benefit, whereas MIX
      administration prevented further worsening of MS symptoms. We stress that only
      specialists with a broad experience in intraspinal triamcinolone acetonide
      application and MIX administration should perform both kinds of therapy only
      after a careful information and risk-benefit evaluation in cooperation with the
      patient. Future trials will show the efficacy of combination of both treatment
      approaches in chronic progressive patients with MS.

PMID- 16960475
TI  - Apomorphine: a rapid rescue agent for the management of motor fluctuations in
      advanced Parkinson disease.
AB  - Parkinson disease is one of the most common neurodegenerative diseases in the
      United States, and the number of late stage patients is rising. In advance-stage
      disease, fluctuations in motor function, variability in response to dopaminergic
      therapy, and dyskinesias related to increasing doses of dopamine agonists and
      levodopa, present a variety of challenges to a managing physician. Traditional
      methods of treatment have concentrated on therapies to anticipate or prevent
      states of poor motor function. With the approval of apomorphine as a rapid
      acting, subcutaneous injectable anti-Parkinson disease therapy, these off periods
      may now be treated with apomorphine as a "rescue" medication when they occur.
      This article reviews the pharmacology of apomorphine, the clinical data that
      support its use and suggest dosing and methods for initiating therapy in this
      challenging population of patients with Parkinson disease.

PMID- 16960477
TI  - Imaging of cerebral blood flow and metabolism.
AB  - PURPOSE OF REVIEW: To review the techniques for imaging cerebral blood flow and
      metabolism following injury to the brain. RECENT FINDINGS: Xenon enhanced
      computerized tomography (Xenon CT), CT perfusion and single photon emission CT
      provide measurements of cerebral perfusion, while positron emission tomography
      (PET), and magnetic resonance imaging and spectroscopy (MRI and MRS) are able to
      assess both perfusion and cerebral metabolism. Xenon CT and CT perfusion are
      readily available and have proved useful in a variety of causes of brain injury.
      PET is an extremely useful research tool for defining cerebral physiology, but is
      limited in its availability. Despite the continuing development of MRI and MRS
      imaging, the scanning environment remains hostile for critically ill patients,
      and further research is required before the techniques become generally
      available. SUMMARY: Imaging of cerebral blood flow and metabolism has been shown
      to be useful following a variety of causes of brain injury, as it can help to
      define the cause and extent of injury, identify appropriate treatments and
      predict outcome. Imaging based on CT techniques (Xenon CT and CT perfusion) can
      be implemented easily in most hospital centres, and are able to provide
      quantitative perfusion data in addition to structural images.

PMID- 16960478
TI  - Brain protection by anesthetic agents.
AB  - PURPOSE OF REVIEW: Patients at risk for perioperative stroke, or those who have
      suffered recent cerebral injury, may benefit from neuroprotective properties of
      anesthetic agents during surgery. This manuscript reviews recent clinical and
      experimental evidence for neuroprotective effects of common anesthetic agents,
      and presents potential mechanisms involved in anesthetic neuroprotection. RECENT
      FINDINGS: Although strong experimental data support a neuroprotective potential
      of several anesthetic agents, specifically isoflurane and xenon, consistent long
      term protection by either agent has not been demonstrated. Unfortunately, there
      is a lack of clinical studies that would support the use of any one anesthetic
      agent over the others. Mechanisms of neuroprotection by anesthetic agents appear
      to involve suppression of excitatory neurotransmission, and potentiation of
      inhibitory activity, which may contribute to the reduction of excitotoxic injury.
      Activation of intracellular signaling cascades that lead to altered expression of
      protective genes may also be involved. SUMMARY: Solid experimental evidence
      supports neuroprotection by anesthetic agents. It is too early to recommend any
      specific agent for clinical use as a neuroprotectant, however. Further study is
      warranted to unravel relevant mechanisms and to appreciate the potential clinical
      relevance of experimental findings.

PMID- 16960479
TI  - Hypothermia for brain protection and resuscitation.
AB  - PURPOSE OF REVIEW: Clinicians are actively looking for an effective brain
      protection technique. With pharmacologic agents, several phase III trials in
      stroke, severe traumatic brain injury, and post-cardiac arrest survivors have
      failed. Hence there is renewed interest in mild to moderate hypothermia for brain
      protection. Phase III clinical trials with hypothermia have been successful only
      in post-cardiac arrest survivors and neonatal hypoxic encephalopathy. This review
      focuses on the possible reasons for our inability to translate into positive
      clinical trials what is observed consistently in laboratory models. RECENT
      FINDINGS: Several factors have been identified for the failure of successive
      hypothermia clinical trials. Patients with severe traumatic brain injury with
      Glasgow Coma Score of 4-7 on admission and those less than 45 years of age and
      neonates with hypoxic encephalopathy are more responsive to hypothermia.
      Similarly, early and effective cooling techniques and titration of hypothermia to
      a defined endpoint are likely to be more effective. New techniques such as local
      cooling of the brain and the combination of hypothermia with drugs are being
      evaluated. SUMMARY: Hypothermia can at present be recommended only for post
      cardiac arrest survivors and in neonatal hypoxic encephalopathy.

PMID- 16960480
TI  - Management of physiological variables in neuroanaesthesia: maintaining
      homeostasis during intracranial surgery.
AB  - PURPOSE OF REVIEW: The recent literature on the perioperative maintenance of
      cerebral homeostasis was reviewed. RECENT FINDINGS: Several studies focused on
      the regulation of cerebral blood flow in patients without intracranial disease;
      therefore, further studies in neurosurgical patients are needed. High
      intracranial pressure and brain swelling can be controlled by the choice of
      anaesthetic agents, and also by optimal positioning of the patient. The use of
      positive end-expiratory pressure may impair cerebral blood flow, but the effects
      of positive end-expiratory pressure seem to depend on the respiratory system
      compliance. The international multicenter study failed to show any benefit from
      intraoperative hypothermia in patients with subarachnoid hemorrhage; similarly,
      the results on corticosteroid therapy in head-injured patients are discouraging.
      Corticosteroid therapy has prompted studies on the control of blood glucose
      levels. While tight glycemic control has been recommended, it can have untoward
      effects manifested as cerebral metabolic stress. SUMMARY: From the clinical point
      of view, the recent research has added only little to the knowledge on the
      management of physiological parameters in neurosurgery. More adequately powered
      studies focusing in specific problems, and having a meaningful aim relative to
      outcome, are needed also in neuroanaesthesia.

PMID- 16960481
TI  - Why we still use intravenous drugs as the basic regimen for neurosurgical
      anaesthesia.
AB  - PURPOSE OF REVIEW: Evolution of neurosurgery mainly trends towards minimally
      invasive and functional procedures including endoscopies, small-size
      craniotomies, intraoperative imaging and stereotactic interventions.
      Consequently, new adjustments of anaesthesia should aim at providing brain
      relaxation, minimal interference with electrophysiological monitoring, rapid
      recovery, patients' cooperation during surgery and neuroprotection. RECENT
      FINDINGS: In brain tumour patients undergoing craniotomy, propofol anaesthesia is
      associated with lower intracranial pressure and cerebral swelling than volatile
      anaesthesia. Hyperventilation used to improve brain relaxation may decrease
      jugular venous oxygen saturation below the critical threshold. It decreases the
      cerebral perfusion pressure in patients receiving sevoflurane, but not in those
      receiving propofol. The advantage of propofol over volatile agents has also been
      confirmed regarding interference with somatosensory, auditory and motor evoked
      potentials. Excellent and predictable recovery conditions as well as minimal
      postoperative side-effects make propofol particularly suitable in awake
      craniotomies. Finally, the potential neuroprotective effect of this drug could be
      mediated by its antioxidant properties which can play a role in apoptosis,
      ischaemia-reperfusion injury and inflammatory-induced neuronal damage. SUMMARY:
      Although all the objectives of neurosurgical anaesthesia cannot be met by one
      single anaesthetic agent or technique, propofol-based intravenous anaesthesia
      appears as the first choice to challenge the evolution of neurosurgery in the
      third millennium.

PMID- 16960482
TI  - Inhalational or intravenous anesthetics for craniotomies? Pro inhalational.
AB  - PURPOSE OF REVIEW: In neurosurgery, anesthesiologists and surgeons focus on the
      same target - the brain. The nature of anesthetics is to interact with brain
      physiology, leading to favorable and adverse effects. Research in neuroanesthesia
      over the last three decades has been dedicated to identifying the optimal
      anesthetic agent to maintain coupling between cerebral blood flow and metabolism,
      keep cerebrovascular autoregulation intact, and not increase cerebral blood
      volume and intracranial pressure. RECENT FINDINGS: Sevoflurane is less vasoactive
      than halothane, enflurane, isoflurane, or desflurane. The context sensitive half
      life is short and similar to that of desflurane, which translates into fast on
      and offset. Compared with propofol, sevoflurane decreases cerebral blood flow to
      a lesser extent, while cerebral metabolism is suppressed to the same degree.
      Sevoflurane does not increase intracranial pressure, while propofol decreases
      intracranial pressure. SUMMARY: In neurosurgical patients with normal
      intracranial pressure, sevoflurane might be a good alternative to propofol. In
      patients with reduced intracranial elastance, caused by space occupying lesions,
      with elevated intracranial pressure or complex surgical approaches, propofol
      should remain first choice.

PMID- 16960483
TI  - Is there a place for local anesthetics structurally different from classical amid
      or ester local anesthetics?
AB  - PURPOSE OF REVIEW: The aim of this review is to describe the pharmacology,
      toxicology and chemistry of the new group of local anesthetics of phenylcarbamic
      acid type. RECENT FINDINGS: Basic esters of alkoxy-substituted phenylcarbamic
      acid have shown high local anesthetic potency, while maintaining a relatively
      safe toxicity profile. Their potency uniquely increases with the decreasing pH of
      the external medium. This is of importance when using local anesthesics in
      inflamed tissues, where the action of common local anesthetics is often
      problematic. SUMMARY: The most potent phenylcarbamic anesthetics exceed the
      potency of the most common clinically used local anesthetics 100-300 times. Due
      to the unique pH dependency of these local anesthetics, further study of their
      action is required.

PMID- 16960484
TI  - Antidepressants as local anesthetics: is there a place in regional anesthesia?
AB  - PURPOSE OF REVIEW: Antidepressants have multiple sites of action. Among these,
      the ability to inhibit sodium channels has led to the increased interest in their
      use as local anesthetics. The following review summarizes the results of recent
      studies on this topic. RECENT FINDINGS: Various animal and human models have
      shown that antidepressants exhibit many properties of local anesthetics with an
      extended duration of action. Due to limitations in study designs, however, these
      dramatic effects might have been misinterpreted and therefore possible toxicity
      may not have been recognized. Indeed, more recent studies focusing on toxic
      effects of antidepressants when used as local anesthetics proved this to be the
      case. SUMMARY: Although antidepressants indeed act as potent local anesthetics,
      their use in the clinical setting cannot be recommended as of today due to
      extensive local tissue toxicity.

PMID- 16960485
TI  - Regional anaesthesia and perioperative outcome.
AB  - PURPOSE OF REVIEW: The ongoing debate on the outcome benefits of regional
      anaesthesia and analgesia over general anaesthesia and systemic analgesia has led
      to a large number of recently published papers, in particular systematic reviews
      and meta-analyses that justify a review of the current status of the debate.
      RECENT FINDINGS: Meta-analyses have shown consistently improved analgesia with
      epidural techniques, but the results are by far less consistent with regard to
      other outcomes, in particular morbidity and mortality. Specific outcomes in
      specific types of surgery, however, such as bowel recovery after abdominal
      surgery, can be improved by neuraxial blockade, which also remains the technique
      of choice for obstetric analgesia and anaesthesia. In certain indications,
      peripheral nerve blocks may have the potential to replace neuraxial blocks while
      maintaining the benefits of the regional technique, such as paravertebral blocks
      for thoracotomies. SUMMARY: Although there are a considerable number of recent
      publications on the topic, the complex issues around the effect of regional
      anaesthesia on outcome is not completely resolved, possibly because the data are
      often not procedure specific. In addition, however, it may be that our current
      literature cannot provide a definitive answer.

PMID- 16960486
TI  - How to teach regional anesthesia.
AB  - PURPOSE OF REVIEW: The demand for peripheral nerve blocks and neuroaxial blocks
      from both patients and surgeons has increased over the last few years. This
      change in attitude towards regional anesthesia is prompted by the insight that
      adequate perioperative pain management leads to earlier ambulation, shorter
      hospital stay, reduced cost and increased patient satisfaction. To avoid serious
      complications of these techniques structured residency programs need to be
      available. RECENT FINDINGS: Until 2004, the Residency Review Committee for
      Anesthesiology in the United States required a minimum of 50 epidurals, 40
      spinals and 40 peripheral nerve blocks during residency. Similarly, the German
      Society for Anesthesia and Intensive Care required 100 neuroaxial blocks and 50
      peripheral nerve blocks. In 2004 the American Society of Regional Anesthesia and
      Pain Medicine endorsed standardized guidelines for regional anesthesia
      fellowships which regulate the administrative, equipment and educational demands.
      SUMMARY: This review introduces the reader to the different teaching methods
      available, including cadaver workshops, three-dimensional videoclips, video
      filming, ultrasound guidance and acoustic assist devices as well as demonstrating
      their advantages and disadvantages. Moreover, an overview is given of future
      residency training programs, which integrate administrative, material and
      educative demands as well as the teaching means into the daily clinical routine.

PMID- 16960487
TI  - Complications of regional anesthesia.
AB  - PURPOSE OF REVIEW: The use of regional anesthesia, either alone or as an adjunct
      to general anesthesia, is at an all-time high. Demonstrated benefits include
      reduced side effects, more efficient use of facilities and enhanced patient
      satisfaction with the improved postoperative pain relief. New advances in
      equipment, techniques and medications have been incorporated over the past 10
      years, and especially over the last 2 years. As the number of practitioners and
      procedures increase, the number of complications may rise as well. RECENT
      FINDINGS: The specific issues of nerve damage, treatment of local anesthetic
      toxicity with lipid solutions and prevention of wrong-sided procedures are
      examined with special reference to recent publications. SUMMARY: Specific needle
      shapes, appropriate pharmacologic resuscitation from intravascular injection of
      local anesthetics and institutional procedures to positively identify patients
      and the correct block location are all part of a strategy to minimize the
      occurrence of adverse outcomes and to mitigate the consequences of those adverse
      events when they do occur. More importantly, these are changes that can be
      instituted immediately with minimal expense to the institution and great benefit
      to the patient.

PMID- 16960488
TI  - The critically ill patient and regional anesthesia.
AB  - PURPOSE OF REVIEW: The review presents an overview of indications, limitations
      and practical aspects of regional anesthesia and analgesia in critically ill
      medical and surgical patients. RECENT FINDINGS: A Medline search from 1966 to
      2006 with the search terms regional anesthesia, regional analgesia, critically
      ill and nerve blocks, as well as a search of the Cochrane Library, revealed no
      studies specifically designed to evaluate the use of regional anesthesia and
      analgesia in the intensive care unit setting. The available evidence is limited
      to case reports, cohort studies and expert opinions, and relies heavily on
      extrapolation from studies primarily designed to examine intraoperative
      management of surgical patients in whom an intensive care unit admission was part
      of the perioperative course. SUMMARY: Regional anesthesia and analgesia in the
      critically ill can help to improve respiratory function, bowel function, mental
      status and patient comfort secondary to its opioid-sparing effects. Limitations
      for the use of regional anesthetic techniques are mainly associated with bleeding
      risks, hemodynamic side-effects, difficulties in neurologic assessment and the
      potential of local anesthetic toxicity.

PMID- 16960489
TI  - The influence of new antithrombotic drugs on regional anesthesia.
AB  - PURPOSE OF REVIEW: Antithrombotic drugs are known to increase the risk of spinal
      epidural hematoma after neuraxial blockade. During the last few years, several
      new anticoagulants have been introduced, some of them more potent than the drugs
      currently available. More potency, however, may also indicate a higher risk of
      bleeding. RECENT FINDINGS: Case series from the last few years indicate that
      spinal epidural hematoma is more common then previously estimated, with a
      prevalence from 1: 100,000 in obstetric patients to as high as 1: 3,600 in female
      orthopedic patients. In order to diminish this risk, most national societies have
      issued guidelines in which time intervals were established between administration
      of antithrombotic drugs and performance of neuraxial blockade. SUMMARY:
      Guidelines are perceived to be capable of reducing the incidence of spinal
      epidural hematoma with the inherent risk of permanent paraplegia. These
      guidelines, however, will only be a valuable aid for clinicians if they are
      constantly updated and newer antithrombotic drugs are included. Although the
      resurge of peripheral nerve blocks may diminish patient hazards, deep nerve
      blocks such as lumbar sympathetic blockade are not devoid of serious
      complications and should probably be handled in the same way as neuraxial
      blockade.

PMID- 16960490
TI  - From preemptive to preventive analgesia.
AB  - PURPOSE OF REVIEW: Much effort has been taken to prove that a treatment initiated
      before surgery is more effective in reducing postoperative pain compared with the
      same intervention started after surgery. Clinical studies failed to demonstrate
      major clinical benefits of preemptive analgesia, however, and the results of
      recent systemic reviews are equivocal. The present review will discuss recent
      clinical as well as experimental evidence of preemptive analgesia and examine the
      implications of a preventive postoperative pain treatment. RECENT FINDINGS:
      Recent preclinical and clinical studies give strong evidence that neuronal
      hypersensitivity and nociception after incision is mainly maintained by the
      afferent barrage of sensitized nociceptors across the perioperative period. This
      is in contrast to pain states of other origin in which prolonged hypersensitivity
      is initiated during the injury. Therefore, not timing but duration and efficacy
      of an analgesic and antihyperalgesic intervention are most important for treating
      pain and hyperalgesia after surgery. SUMMARY: Extending a multimodal analgesic
      treatment into the postoperative period to prevent postoperative pain may be
      superior compared with preemptive analgesia. In the future, appropriate drug
      combinations, drug concentrations and duration of preventive strategies need to
      be determined to be most beneficial for the management of acute and chronic pain
      after surgery.

PMID- 16960491
TI  - Perioperative pain.
AB  - PURPOSE OF REVIEW: Incisional pain remains underevaluated and undermanaged while
      evidence is growing that perioperative treatments strongly influence patients'
      outcome. The present review examines the recent developments in mechanisms
      underlying perioperative pain and questions current understanding of incisional
      pain features observed in patients. RECENT FINDINGS: Experimental models of
      incisional pain have highlighted specific mechanisms underlying perioperative
      pain plasticity, i.e. sensitization of sensory processing, clinically expressed
      by the development of hyperalgesia. In patients, however, the long-term impact of
      sensory system sensitization, e.g. development of residual pain, as well as the
      effects of perioperative pain management on sensitization, are still poorly
      understood, partly because most of the trials assess only the subjective
      experience of pain (by evaluation of either pain intensity or analgesic needs)
      instead of directly measuring objective changes (i.e. hyperalgesia) with
      quantitative sensory testing. SUMMARY: Experimental studies and recent clinical
      trials using objective measures of sensory processing sensitization induced by
      surgical incision have shown the importance of hyperalgesia in perioperative
      pain. Effective perioperative block of nociceptive inputs from the wound as well
      as use of antihyperalgesic and analgesic drugs in combination seem the best way
      to control postoperative pain and specifically to prevent central sensitization.

PMID- 16960492
TI  - State of the art of paracetamol in acute pain therapy.
AB  - PURPOSE OF REVIEW: This review highlights new insights into the mechanism of
      action of paracetamol (acetaminophen) and therapeutic schemes. RECENT FINDINGS:
      Paracetamol, a centrally acting inhibitor of cyclooxygenases, has weak peripheral
      effects recently demonstrated. Paracetamol is nevertheless devoid of side effects
      commonly observed with the use of nonsteroidal anti-inflammatory drugs.
      Paracetamol is available by the oral, rectal, and, more recently, intravenous
      routes of administration. Paracetamol efficacy is surgical procedure dependent.
      The analgesic efficacy of a 2-g starting dose of intravenous paracetamol is
      superior to the recommended dose of 1 g in terms of magnitude and duration of
      analgesic effect. The usual scheme of administration (1 g every 6 hours) has a
      less than 10-mg sparing effect on 24-hour morphine consumption and consequently
      does not significantly reduce morphine side effects. The combination of
      nonsteroidal anti-inflammatory drugs and paracetamol is more effective than
      paracetamol alone, but the benefit is unclear when compared with nonsteroidal
      anti-inflammatory drugs used alone. SUMMARY: Further studies are required to
      assess the opioid-sparing effect and complementary analgesic effect of new
      intravenous paracetamol therapeutic schemes.

PMID- 16960493
TI  - Advances in treatment of complex regional pain syndrome: recent insights on a
      perplexing disease.
AB  - PURPOSE OF REVIEW: The paper is a critical appraisal of recent advances in the
      treatment of complex regional pain syndrome. Rapidly changing concepts related to
      the pathophysiology of this disease has transformed its current management and
      necessitates an updated review of the literature. RECENT FINDINGS: Chronic
      regional pain syndrome is a perplexing disease that continues to challenge
      researchers with respect to its cause and treatment. Recent modification to
      diagnostic criteria has enabled clinicians to diagnose this disease in a more
      consistent fashion. Emerging data indicate a possible role of inflammation in the
      overall pathophysiology and have led to treatment trials with newer anti
      inflammatory medications. Certain 'conventional' interventional techniques have
      been recently scrutinized. A few novel therapeutic options like graded imagery
      are also outlined. SUMMARY: Enhanced insight into the pathophysiology of chronic
      regional pain syndrome has modified current clinical practice and the focus of
      research. Certain 'standard' therapeutic options for chronic regional pain
      syndrome have failed the test of time while others have prevailed. New options
      have recently been evaluated and have shown promising early results. Knowledge of
      recent advances in chronic regional pain syndrome will help pain physicians
      provide optimal care to these patients.

PMID- 16960494
TI  - Recent clinical advances in diabetic polyneuropathy.
AB  - PURPOSE OF REVIEW: Recent dramatic increases in the incidence and prevalence of
      diabetes make an understanding of chronic symmetric sensorimotor diabetic
      polyneuropathy, the most common and problematic of chronic diabetic
      complications, essential for a wide range of medical practitioners. RECENT
      FINDINGS: The demonstration of neuropathic dysfunction in patients with
      prediabetes or impaired glucose tolerance emphasizes the susceptibility of
      peripheral nerve fibers, especially small A delta fibers and C fibers, to
      relatively mild, short-duration hyperglycemia. New testing can reveal peripheral
      nerve dysfunction prior to clinical neuropathic symptoms and signs. In the
      absence of effective medications to halt or reverse nerve damage or promote nerve
      regeneration, early diagnosis of diabetic polyneuropathy, followed by tight
      glycemic control with diet and exercise, offers the best opportunity to prevent
      progressive symptoms of sensory loss, pain, autonomic dysfunction, ulcerations,
      and amputations. Some patients with impaired glucose tolerance have a reversal of
      neuropathic features with tight glycemic control. Nonpharmacologic therapies for
      neuropathic pain in diabetic polyneuropathy appear promising. SUMMARY: Tight
      glycemic control, especially early in diabetes, is the best approach to
      minimizing the prevalence and severity of diabetic polyneuropathy and makes
      research into the deleterious effects of even mild hyperglycemia imperative.

PMID- 16960495
TI  - Current world literature.

PMID- 16960497
TI  - Biomarkers for atherosclerosis: pathophysiological role and pharmacological
      modulation.
AB  - PURPOSE OF REVIEW: The aim of this article is to discuss the potential value of
      biomarkers for atherosclerosis in the assessment of risk for cardiovascular
      disease, in the pathogenesis of atherosclerosis, and in the monitoring of
      pharmacological treatment. RECENT FINDINGS: In an attempt to improve global
      cardiovascular risk prediction, considerable effort has been made in the
      discovery and characterization of soluble biomarkers which can go beyond the
      measure of total and LDL cholesterol levels. In particular, circulating molecules
      related to chronic inflammation have emerged as potential biomarkers for
      atherosclerosis. Evidence, obtained from in-vitro and in-vivo experimental
      models, has also documented that the majority of biomarkers play a pathological
      role in atherogenesis. Multiple screening of different biomarkers may therefore
      improve the assessment of risk, diagnosis, and prognosis for cardiovascular
      disease. In addition, soluble biomarkers have been shown to be modulated by
      hypolipidemic drugs and to be potentially useful in determining the clinical
      benefits of pharmacological therapies that do not alter serum lipid levels.
      SUMMARY: Altered levels of soluble biomarkers are associated with cardiovascular
      disease, and profiling of multiple biomarkers for atherosclerosis will be a
      useful indicator for better risk assessment, diagnosis, and prognosis, as well as
      monitoring pharmacological treatments for atherosclerosis.

PMID- 16960499
TI  - Controlling oxidative stress as a novel molecular approach to protecting the
      vascular wall in diabetes.
AB  - PURPOSE OF REVIEW: In diabetes, oxidative stress plays a key role in the
      pathogenesis of vascular complications; therefore an antioxidant therapy would be
      of great interest in this disease. RECENT FINDINGS: Hyperglycemia directly
      promotes an endothelial dysfunction--inducing process of overproduction of
      superoxide at the mitochondrial level. This is the first and key event able to
      activate all the pathways involved in the development of vascular complications
      of diabetes. It has recently been shown that statins, angiotensin-converting
      enzyme inhibitors, angiotensin II type 1 blockers, calcium channel blockers, and
      thiazolidinediones have a strong intracellular antioxidant activity. SUMMARY:
      Classic antioxidants, such as vitamin E, failed to show beneficial effects on
      diabetic complications probably because their action is only "symptomatic". The
      preventive activity against hyperglycemia-induced oxidative stress shown by
      statins, angiotensin-converting enzyme inhibitors, angiotensin II type 1
      blockers, calcium channel blockers, and thiazolidinediones justifies use of these
      compounds for preventing complications in patients with diabetes, in whom
      antioxidant defences have been shown to be defective.

PMID- 16960498
TI  - Clinical applications of circulating oxidized low-density lipoprotein biomarkers
      in cardiovascular disease.
AB  - PURPOSE OF REVIEW: The aim of this article is to review, analyze and interpret
      the growing body of evidence on circulating oxidized low-density lipoprotein and
      its relationship to diagnosis and prognosis of cardiovascular disease. RECENT
      FINDINGS: Previous studies focused on indirect measures of oxidative stress such
      as susceptibility of low-density lipoprotein to oxidation and measurement of
      autoantibodies to oxidized low-density lipoprotein. The generation of monoclonal
      antibodies recognizing distinct oxidation-specific epitopes has allowed the
      development of sensitive and specific assays to measure circulating oxidized low
      density lipoprotein. Recent work in human populations has demonstrated that
      circulating oxidized low-density lipoprotein is associated with preclinical
      atherosclerosis, coronary and peripheral arterial atherosclerosis, acute coronary
      syndromes and vulnerable plaques. Several studies have also suggested that
      elevated levels of oxidized low-density lipoprotein are a prognostic indicator of
      cardiovascular outcomes. In addition, it has been shown that lipoprotein(a) is
      the primary carrier of oxidized phospholipids in the circulation of humans,
      suggesting additional mechanisms through which lipoprotein(a) may be pro
      atherogenic. SUMMARY: Research on circulating oxidized low-density lipoprotein
      biomarkers is rapidly accelerating and providing novel insights into the
      pathophysiology of cardiovascular disease. Future studies will further assess the
      clinical utility of oxidized low-density lipoprotein biomarkers by determining
      their prognostic value in the diagnosis and prognosis of cardiovascular disease
      and will also evaluate the relative merit of specific assays by performing
      comparative studies.

PMID- 16960500
TI  - Cannabinoid receptors in atherosclerosis.
AB  - PURPOSE OF REVIEW: Recent findings suggesting that cannabinoid receptors are
      potential targets for the treatment of atherosclerosis are reviewed. RECENT
      FINDINGS: Cannabinoids, such as Delta9-tetrahydrocannabinol, the major
      psychoactive compound of marijuana, their synthetic analogs and endogenous
      cannabinoid ligands, produce their biological effects by interacting with
      specific receptors. In the apolipoprotein E knockout mouse model of
      atherosclerosis, Delta9-tetrahydrocannabinol was shown to inhibit disease
      progression through pleiotropic effects on inflammatory cells. Blocking of
      cannabinoid receptor CB2, the main cannabinoid receptor expressed on immune
      cells, abolished the observed effects. The development of novel cannabinoid
      receptor ligands that selectively target CB2 receptors or pharmacological
      modulation of the endocannabinoid system might offer novel therapeutic strategies
      in the treatment of atherosclerosis. Several reports demonstrating an implication
      of the endocannabinoid system in different inflammatory conditions support this
      hypothesis. SUMMARY: The immunomodulatory capacity of cannabinoids is now well
      established and suggests a broad therapeutic potential of cannabinoids for a
      variety of conditions, including atherosclerosis. New strategies based on
      nonpsychotropic cannabinoid receptor ligands or compounds modulating
      endocannabinoid synthesis or stability might solve the problem of the unwanted
      side effects associated with cannabinoid administration.

PMID- 16960501
TI  - Multiple roles of Toll-like receptor signaling in atherosclerosis.
AB  - PURPOSE OF REVIEW: Toll-like receptors are key regulators of both innate and
      adaptive immune responses. This review outlines the recently emerged multiple
      roles of Toll-like receptor signaling in atherosclerosis. RECENT FINDINGS: Mice
      deficient in TLR4, TLR2 and MyD88 all have reduced atherosclerosis which
      establishes that Toll-like receptor-dependent pathways contribute to disease
      development. Although it is likely that total "infectious burden" contributes to
      atherosclerosis progression, endogenous ligands may also initiate and modulate
      Toll-like receptor signaling pathways. CD36, with established roles in
      recognition of endogenous ligands and atherosclerotic disease, facilitates TLR2
      signaling and might therefore represent a bridge between endogenous lipid ligands
      and Toll-like receptor pathways. Furthermore, lipoprotein oxidation generates
      ligands that activate Toll-like receptor pathways. At the same time, Toll-like
      receptor activation may be inhibited by accumulating oxidized phospholipids,
      which could result in reduced dendritic cell maturation and impaired
      immunological priming. SUMMARY: Activation of Toll-like receptor signaling can
      promote atherosclerosis by multiple mechanisms, while some beneficial Toll-like
      receptor pathways may be inhibited by lipid accumulation. Due to their central
      role in the disease process, Toll-like receptor signaling pathways represent a
      target of immunomodulatory therapy with the goal of tipping the balance from
      excessive chronic inflammation towards resolution of inflammation, while not
      compromising host defense or atheroprotective immune functions.

PMID- 16960502
TI  - Enhanced extracellular lipid accumulation in acidic environments.
AB  - PURPOSE OF REVIEW: Binding of apolipoprotein B-100-containing lipoproteins (VLDL,
      IDL, and LDL) to proteoglycans and modifications of the lipoproteins, whether
      bound or unbound, are key processes in atherogenesis. The complex interplay
      between binding and modification has been studied at neutral pH conditions. It
      has been demonstrated that during atherogenesis the extracellular pH of the
      lesions decreases. We summarize findings suggesting that lipoprotein binding and
      modification are enhanced at acidic pH. RECENT FINDINGS: Many enzymes found in
      the arterial intima, such as secretory sphingomyelinase and cathepsins, are able
      to hydrolyze lipoproteins in vitro. These enzymes function optimally at slightly
      acidic pH (pH 5.5-6.5), and are likely to act on lipoproteins optimally in the
      acidic plaque areas. Also, the ability of human aortic proteoglycans to bind
      native VLDL, IDL, and LDL is dramatically increased at acidic pH; this binding
      can be further increased if these apolipoprotein B-100-containing particles are
      hydrolytically modified. SUMMARY: Recent in-vitro findings suggest that in areas
      of atherosclerotic arterial intima where the extracellular pH is decreased,
      binding of apolipoprotein B-100-containing lipoproteins to proteoglycans and
      modification of the lipoproteins by acidic enzymes are enhanced. The pH-induced
      amplification of these processes will lead to enhanced extracellular accumulation
      of lipoproteins and accelerated progression of the disease.

PMID- 16960503
TI  - Untangling the role of amyloid in atherosclerosis.
AB  - PURPOSE OF REVIEW: Amyloid deposits are a defining feature of several age-related
      and debilitating diseases. Their widespread presence in atherosclerotic plaques
      suggests a potential role in lesion development. This review discusses the
      proteins known to accumulate in atheroma and examines the evidence that amyloid
      like structures activate macrophage signaling pathways linked to inflammation and
      prothrombotic potential. RECENT FINDINGS: Numerous proteins that accumulate in
      atherosclerotic plaques form amyloid fibrils in vivo, including apolipoproteins,
      beta-amyloid, and alpha1-antitrypsin. In addition, oxidation or enzymatic
      modification of low-density lipoproteins induces a structural reorganization of
      the particle, including the acquisition of amyloid-like properties. Similarly,
      glycation of serum albumin, as observed in diabetes, is accompanied by the
      formation of aggregates with all the hallmarks of amyloid. Several receptors
      implicated in atherogenesis modulate the fate of amyloid fibrils by mediating
      their clearance (scavenger receptors A and B-I), activating inflammatory
      signaling cascades (receptor for advanced glycation endproducts), or both (CD36).
      Finally, recent studies indicate that amyloid deposition accelerates diet-induced
      atherosclerosis in mice. SUMMARY: Given the substantial evidence that amyloid
      fibrils or preamyloidogenic species are cytotoxic, the aberrant deposition of
      amyloid in the intima may be pathologically important in vascular inflammation
      and the promotion of atherosclerosis.

PMID- 16960504
TI  - Angiogenesis in atherosclerosis: gathering evidence beyond speculation.
AB  - PURPOSE OF REVIEW: The present review summarizes evidence for several functions
      of neovascularization in plaque growth that sustain perfusion beyond limits of
      diffusion from the artery lumen and outer adventitial vasa vasorum, deposit
      proatherogenic plasma molecules, recruit immune cells and progenitors, and
      promote intraplaque hemorrhage. Recent approvals of antiangiogenesis drugs for
      clinical use in cancer and macular degeneration improve the feasibility of
      testing whether such agents inhibit plaque angiogenesis and incidental
      atherosclerosis. RECENT FINDINGS: Improvements in large and small animal models
      of atherosclerosis and knowledge of the molecular regulation of angiogenesis in
      development and disease have advanced understanding of plaque angiogenesis.
      Genetic modifications of angiogenesis molecules in mouse strains susceptible to
      atherosclerosis provide experimental means to identify native molecules that
      regulate plaque angiogenesis. Studies of plaque angiogenesis are aided by micro
      computed tomography techniques that image vasa vasorum anatomy in relation to the
      atheroma. SUMMARY: Greater knowledge of plaque angiogenesis regulation is needed
      to design treatments that target the most critical regulatory pathways.
      Evolutions in angiogenesis inhibitor treatments for cancer and other diseases
      call for a need to understand the distinct cardiovascular profiles of different
      agents to rationally combine agents for optimal selectivity and efficacy in the
      intended vascular bed.

PMID- 16960505
TI  - Do metalloproteinases destabilize vulnerable atherosclerotic plaques?
AB  - PURPOSE OF REVIEW: Atherosclerotic plaque rupture and thrombosis underlie most
      myocardial infarctions. Matrix metalloproteinases are a family of enzymes that
      remodel the extracellular matrix. Metalloproteinases could stabilize rupture
      prone plaques by promoting smooth muscle cell migration and proliferation.
      Alternatively, metalloproteinases could destabilize vulnerable plaques by
      promoting matrix destruction, angiogenesis, leucocyte infiltration, and
      apoptosis. Evidence is reviewed from genetically modified mice and human
      biomarker and genetic studies that sheds light on this dual role of
      metalloproteinases. RECENT FINDINGS: Inhibition of metalloproteinases in mice
      using tissue inhibitors of metalloproteinases increases plaque stability;
      however, double knockouts of apolipoprotein E with matrix metalloproteinase 2, 3,
      7, 9, 12, and 13 have more or less stable plaques, consistent with harmful or
      protective effects of individual metalloproteinases. Overexpression studies in
      mice or rabbits show that high activities of matrix metalloproteinase 9 and 12
      decrease stability. Biomarker and human genetic studies demonstrate that
      increased metalloproteinase activity is associated with vascular repair or
      myocardial infarction. SUMMARY: Recent studies reinforce evidence for a dual role
      of matrix metalloproteinases in plaque stabilization and rupture, which probably
      depends on the stage, site, and severity of disease. Dysregulated
      metalloproteinase activity in end-stage coronary artery disease appears a valid
      target for therapy.

PMID- 16960506
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 16960507
TI  - Nutrition and metabolism.

PMID- 16960508
TI  - Genetics and molecular biology: rationale for targeting high-density lipoprotein
      cholesterol for therapeutic intervention.

PMID- 16960509
TI  - Lipid metabolism.

PMID- 16960510
TI  - Atherosclerosis: metabolic syndrome--a science or not a science?

PMID- 16960511
TI  - Therapy and clinical trials.

PMID- 16960512
TI  - Selective serotonin reuptake inhibitors and rhabdomyolysis after eccentric
      exercise.
AB  - PURPOSE: The purpose of this report was to review three cases of clinically
      significant rhabdomyolysis that developed in research subjects after completing
      an eccentric exercise protocol. All three cases occurred in subjects who reported
      use of selective serotonin reuptake inhibitors (SSRI). METHODS: Sixty-three
      subjects enrolled in the study. Subjects performed 15 sets of 15 repetitions of
      maximal eccentric contractions of the elbow flexors. Subjects were then monitored
      on a daily basis for development of delayed onset muscle soreness (DOMS).
      Subjects received either microcurrent electrical neuromuscular stimulation (MENS)
      or sham treatment. RESULTS: Three subjects developed clinically significant
      rhabdomyolysis after performing this exercise protocol. Affected subjects were
      the only subjects who reported use of SSRI during the study period. CONCLUSION:
      This report raises suspicion of SSRI use as a predisposing factor to muscle
      injury after eccentric exercise.

PMID- 16960513
TI  - Exercise-induced systemic effects in muscle-wasted patients with COPD.
AB  - PURPOSE: Physical exercise is known to induce an acute inflammatory response and
      oxidative stress in healthy subjects and patients with chronic obstructive
      pulmonary disease (COPD). Increasing evidence associates systemic inflammation
      and oxidative stress with muscle wasting and muscle dysfunction in COPD. In the
      present study, it was hypothesized that exercise-induced systemic inflammatory
      and oxidative responses in muscle-wasted COPD patients are increased compared
      with non-muscle-wasted patients and healthy subjects. METHODS: Pulmonary
      function, body composition, and quadriceps muscle strength were measured in 10
      muscle-wasted (fat-free mass index (FFMI) < 16 kg x m(-2) (men), < 15 kg x m(-2)
      (women)), 10 non-muscle-wasted COPD patients, and 10 healthy subjects. Systemic
      inflammation (C-reactive protein (CRP), leukocytes, cytokines) and oxidative
      stress (production of reactive oxygen species (ROS) by neutrophils, plasma
      antioxidant capacity, protein oxidation, lipid peroxidation, oxidized to reduced
      glutathione ratio (GSSG/GSH)) were determined before and after maximal and
      submaximal (50% of maximal work rate) cycle ergometry. RESULTS: Low-grade
      systemic inflammation was significantly (P < 0.05) elevated in all COPD patients
      and tended to be highest in muscle-wasted patients. A decreased antioxidant
      status (plasma antioxidant capacity, P < 0.05; GSH, P < 0.05) and increased
      protein oxidation (P < 0.001) reflected increased basal oxidative stress in
      muscle-wasted COPD patients compared with both other groups. Both maximal and
      submaximal exercise caused increased inflammatory (IL-6, +1.1 pg. x mL(-1) vs
      rest, P < 0.05) and oxidative responses (ROS release by neutrophils, + 32%;
      GSSG/GSH + 29%; lipid peroxidation, + 30% vs rest) in muscle-wasted COPD
      patients, which were less pronounced or not observed in non-muscle-wasted
      patients and healthy subjects. CONCLUSIONS: These data indicate that both maximal
      and submaximal exercise induce increased systemic inflammatory and oxidative
      responses in muscle-wasted COPD patients compared with non-muscle-wasted patients
      and healthy subjects.

PMID- 16960514
TI  - Tibialis anterior volumes and areas in ACL-injured limbs compared with
      unimpaired.
AB  - PURPOSE: Past research has shown that subjects with ACL injuries show activation
      differences and atrophy in the muscles that cross the knee, including the
      gastrocnemii, which predominately act at the ankle. However, it is not known how
      the other ankle muscles that do not cross the knee are affected. We focused on
      the two muscles that control the ankle, the soleus and tibialis anterior muscles,
      to see how they were affected by an ACL injury. We hypothesized that the ankle
      muscles of subjects with ACL injuries that did not require surgery (copers) would
      be more like normals and that the muscles of subjects with ACL injuries who
      required surgery to return to normal activity (noncopers) would atrophy. METHODS:
      Twenty-seven subjects were divided into three even categories: unimpaired
      subjects, copers, and noncopers. Axial spin-echo T1-weighted MRI images were used
      to digitally reconstruct the tibialis anterior and the soleus. We used the
      digitally reconstructed muscles to determine the peak cross-sectional area and
      volume of each muscle. RESULTS: The copers' tibialis anterior muscles were
      similar to the unimpaired subjects, but, surprisingly, the noncoper's tibialis
      anterior muscles of the injured leg were larger than those of their uninjured
      legs (P < 0.05). In the soleus, the results showed a trend of not being affected.
      CONCLUSION: The increase in size of the tibialis anterior in noncopers may have
      been caused by altered gait patterns in noncopers. We believe this is due to
      either an ankle-stiffening strategy during heel strike or from the inversion of
      the foot causing external rotation of the tibia as a stabilizing technique for
      the knee.

PMID- 16960515
TI  - Moderate resistance training and vascular health in overweight women.
AB  - PURPOSE: Impaired endothelial function has been implicated as an initial step in
      the pathogenesis of atherosclerosis leading to cardiovascular disease (CVD).
      Aerobic exercise improves vascular function and reduces risk of CVD morbidity and
      mortality; however, the effects of resistance training on vascular function
      remains unclear. Thus, the aim of this study was to examine the effects of 1 yr
      of resistance training (RT) on vascular structure and function in overweight but
      otherwise healthy eumenorrheic women. METHODS: Study participants consisted of 30
      (15 control, 15 RT) overweight (BMI > 25 kg x m(-2)) women, aged 24-44 yr,
      studied before and after a 1-yr RT intervention. Vascular structure and function
      were assessed via noninvasive ultrasound imaging of the carotid and brachial
      arteries, respectively. Body composition, blood pressure, and fasting blood
      lipids and glucose also were measured. RESULTS: The RT group demonstrated a
      significant mean improvement in one-repetition maximum bench press following 1 yr
      of RT (P < 0.05). There also was a significant increase in lean body mass in the
      RT group compared with the control group (P = 0.04). There were no training
      associated changes in blood pressure, fasting blood lipids, glucose, or insulin
      levels. Although there was no change in carotid artery intimamedia thickness,
      peak flow-mediated dilation significantly improved in the RT group (P < 0.05).
      CONCLUSION: The principal significant finding in this study was the initial
      demonstration that RT alone can improve brachial artery endothelial function in
      overweight eumenorrheic women.

PMID- 16960516
TI  - Do changes in lung function predict high-altitude pulmonary edema at an early
      stage?
AB  - PURPOSE: Ascent to high altitude is associated with alterations in lung function.
      The mechanisms of these changes and whether they reflect early stages of high
      altitude pulmonary edema (HAPE) has been debated. Therefore, we investigated the
      time course of pulmonary function in relation to hemodynamics and clinical
      symptoms in mountaineers ascending rapidly to high altitude. METHODS: In 26
      unacclimatized subjects we assessed spirometry, single-breath nitrogen washout,
      diffusing capacity (DLCO), and Doppler echocardiography in Zurich, 490 m, after
      climbing within 24 h to Monte Rosa, 4559 m, and after one night at 4559 m.
      RESULTS: Mean (+/- SD) FVC fell from 103 +/- 9% predicted in Zurich to 96 +/- 10%
      predicted at 4559 m, FEV1/FVC increased from 0.82 +/- 0.06 to 0.84 +/- 0.08, and
      closing volume increased from 0.35 +/- 0.14 to 0.44 +/- 0.11 L above residual
      volume (P < 0.05, all changes). On the following day at 4559 m, closing volume
      remained elevated in 9 of 21 subjects who had a lower DLCO but similar pulmonary
      artery systolic pressures compared with the remaining 12 subjects (40 +/- 8 vs 43
      +/- 7 mm Hg, P = NS). None of the subjects had overt HAPE. CONCLUSION: We
      conclude that changes in pulmonary function after rapid ascent to high altitude
      were consistent with interstitial fluid accumulation, but they were not related
      to changes in pulmonary artery pressure. Individual lung function responses to
      high-altitude exposure varied largely and did not predict subsequent HAPE.

PMID- 16960517
TI  - Epidemiology of stress fracture and lower-extremity overuse injury in female
      recruits.
AB  - PURPOSE: The purpose of this prospective study was to examine rates and risk
      factors for overuse injuries among 824 women during Marine Corps Recruit Depot
      basic training at Parris Island, SC, in 1999. METHODS: Data collected included
      training day exposures (TDE), baseline performance on a standardized 1.5-mile
      timed run, and a pretraining questionnaire highlighting exercise and health
      habits. The women were followed during training for occurrence of stress fracture
      and other lower-extremity overuse injury. RESULTS: There were 868 lower-extremity
      overuse injuries for an overall injury rate of 12.6/1000 TDE. Rates for initial
      and subsequent injury were 8.7/1000 and 20.7/1000 TDE, respectively. There were
      66 confirmed lower-extremity stress fractures among 56 (6.8%) women (1.0/1000
      TDE). Logistic regression modeling indicated that low aerobic fitness (a slower
      time on the timed run (> 14.4 min)), no menses in six or more consecutive months
      during the past year, and less than 7 months of lower-extremity weight training
      were significantly associated with stress fracture incidence. Self-rated fair
      poor fitness at baseline was the only variable significantly associated with
      other non-stress fracture overuse injury during basic training. CONCLUSIONS:
      Among this sample of women, the risk of lower-extremity overuse injury was high,
      with a twofold risk of subsequent injury. The results suggest that stress
      fracture injury might be decreased if women entered training with high aerobic
      fitness and participated frequently in lower-extremity strength training.
      Furthermore, women reporting a history of menstrual irregularity at their initial
      medical exam may require closer observation during basic training.

PMID- 16960518
TI  - Predictors of future anabolic androgenic steroid use.
AB  - PURPOSE: To prospectively study the stability of anabolic androgenic steroid
      (AAS) use and predictors of AAS use, and to investigate whether AAS use alters
      the risk of later emotional and behavioral problems. METHODS: Survey of a
      national sample of Norwegian high school students (age 15-19) in 1994 followed up
      in 1999 (N = 2924). Measures of frequent alcohol intoxication (50+ times per 12
      months), cannabis use (12 months), hard drug use (12 months), being offered
      cannabis, eating problems, conduct problems, sexual debut before age 15, BMI,
      involvement in power sports, perceived physical appearance, and satisfaction with
      body parts were obtained. RESULTS: Life-time prevalence of AAS use were 1.9 and
      0.8% in the follow-up period. Multivariate logistic regression revealed that
      future AAS use was predicted by young age, male gender, previous AAS use,
      involvement in power sports, and frequent alcohol intoxication. AAS use did not
      predict future emotional or behavioral problems other than reducing the risk of
      future frequent alcohol intoxication. CONCLUSION: Frequent alcohol intoxication
      and involvement in power sports appear to predict future AAS use. At the
      population level there was little stability in individual AAS use from
      adolescence to early adulthood. No detrimental effects of AAS use could be
      detected in this study, but low statistical power limits this conclusion.

PMID- 16960519
TI  - Comparison of the 2001 BRFSS and the IPAQ Physical Activity Questionnaires.
AB  - PURPOSE: The 2001 Behavioral Risk Factor Surveillance System (BRFSS) physical
      activity module and the International Physical Activity Questionnaire (IPAQ) are
      used in population studies to determine the prevalence of physical activity. The
      comparability of the prevalence estimates has not been compared in U.S. adults.
      This study compares the physical activity prevalence estimates from the BRFSS and
      the IPAQ. METHODS: A telephone survey was administered to a random sample of
      11,211 U.S. adults aged 18-99 yr who were enrolled in the National Physical
      Activity and Weight Loss Survey. Data were analyzed from 9945 adults who provided
      complete data on the BRFSS and the IPAQ. Prevalence estimates were computed (1)
      applying the BRFSS scoring scheme for both questionnaires (2). Kappa statistics
      were used to compare prevalence estimates generated from the BRFSS and the IPAQ.
      RESULTS: When scored using the BRFSS protocol, agreement between physical
      activity categories was fair (kappa = 0.34-0.49). Prevalence estimates were
      higher on the IPAQ than the BRFSS for the lowest category (inactive) by 0.1-3.9%
      and for the highest category (meets recommendations) by 0.2-9.7%. When scored
      using their own scoring, agreement between physical activity categories was lower
      (kappa = 0.26-0.39). The prevalence estimates on the IPAQ were higher than on the
      BRFSS for the lowest physical activity category by 0.2-13.3% and for the highest
      physical activity category by 0-16.4%. Differences in physical activity
      categories were observed for sex, age, income, education, and body mass index on
      both questionnaires. CONCLUSION: Because of differences in the physical activity
      prevalence estimates, direct comparison of the BRFSS and IPAQ prevalence
      estimates is not recommended.

PMID- 16960520
TI  - Reliability and validity of a school-based physical activity questionnaire.
AB  - PURPOSE: To determine the reliability and validity of the School Health Action,
      Planning and Evaluation System (SHAPES) physical activity questionnaire, a
      machine-readable questionnaire designed to collect data from all students in a
      school from grades 6 to 12 and to provide feedback to the school for planning and
      evaluation. METHODS: Study 1 assessed test-retest reliability by administering
      the questionnaire twice, 1 wk apart to 2812 students in grades 9-12. Study 2
      assessed criterion validity using MTI accelerometers worn consecutively for 7 d,
      and measured height and weight (N = 67, grades 6-12). RESULTS: The overall
      kappa/weighted kappa coefficient for the 1-wk test-retest reliability of the
      questionnaire items indicated moderate agreement (mean 0.57 +/- 0.24). Self
      reported and accelerometer-measured average daily time spent performing moderate
      to vigorous physical activity were significantly correlated (Spearman r = 0.44, P
      < 0.01); however, students tended to overreport physical activity. Height and
      weight were not consistently over- or underreported. Self-reported and measured
      body mass index were significantly correlated (Spearman r = 0.90, P < 0.001).
      Classification of weight status by body mass index was similar using self
      reported values compared with measured values. CONCLUSION: The findings of these
      studies suggest that the SHAPES physical activity questionnaire has acceptable
      reliability and validity and is suitable for use in large-scale school-based data
      collections for child and adolescent populations.

PMID- 16960521
TI  - Power output and muscle myosin heavy chain composition in young and elderly men.
AB  - PURPOSE: Aging is associated with a decline in muscle volume, power output, and
      the velocity at which peak power (Vopt) occurs. The current study aimed to
      examine the relationship between lower-limb power output characteristics, muscle
      myosin heavy chain (MHC) composition, and lean limb volume. METHODS: Lower-limb
      power output during repeated efforts on an inertial sprint cycle and single-leg
      thrusts on the modified Nottingham power rig was studied in seven young and seven
      old males in relation to muscle MHC isoform composition of the vastus lateralis.
      RESULTS: Older subjects produced significantly lower power outputs and Vopt under
      all conditions (P < 0.01) and had lower proportions of fast MHC isoforms (P<
      0.05). Peak power output during cycling was significantly related to lower-limb
      lean volume (r = 0.92, P < 0.05), whereas Vopt during sprint cycling was closely
      related to vastus lateralis MHC-II composition (r = 0.80, P < 0.05). CONCLUSIONS:
      These results provide further evidence of the importance of fast myosin isoform
      composition in the maintenance of dynamic muscle function in later life and
      particularly for maximal cycling performance.

PMID- 16960522
TI  - Effect of an isocaloric carbohydrate-protein-antioxidant drink on cycling
      performance.
AB  - PURPOSE: Fourteen male cyclists were studied to compare the effect of
      carbohydrate-protein-antioxidant beverage (CHOPA) to an isocaloric carbohydrate
      only (CHO) beverage on time to fatigue and muscle damage. METHODS: Subjects
      performed two sets of rides to exhaustion on a cycle ergometer. In each set, the
      first ride was performed at 70% VO2peak, and the second was performed 24 h later
      at 80%. CHO or CHOPA was consumed every 15 min during exercise and immediately
      afterward. Plasma CK and LDH and muscle soreness were measured pre- and
      postexercise. RESULTS: Time to fatigue was not different between CHO and CHOPA at
      70% VO2peak (95.8 +/- 29.7 vs 98.1 +/- 28.7 min), 80% VO2peak (42.3 +/- 18.6 vs
      42.9 +/- 21.8 min), or total performance time (138.1 +/- 39.3 vs 140.9 +/- 43.7
      min). Postexercise CK was increased (P < 0.05) from baseline in CHO (203 +/- 120
      vs 582 +/- 475 U.L(-1)) but not with CHOPA (188 +/- 119 vs 273 +/- 169 U.L(-1)).
      Similarly, LDH values increased over baseline in CHO (437 +/- 46 vs 495 +/- 64
      U.L(-1)) but not with CHOPA (432 +/- 40 vs 451 +/- 43 U.L(-1)). Postexercise CPK
      and LDH were higher after the CHO trial than after the CHOPA trial. Median
      postexercise muscle soreness was higher in CHO (3.0 +/- 5.0) than with CHOPA (1.0
      +/- 3.0). CONCLUSION: No differences in time to fatigue were observed between the
      beverages, despite lower total carbohydrate content in the CHOPA beverage. The
      CHOPA beverage attenuated postexercise muscle damage, as evidenced by CK and LDH
      values, compared with an isocaloric CHO beverage.

PMID- 16960523
TI  - Phosphatidylserine supplementation and recovery following downhill running.
AB  - PURPOSE: This study investigated the effects of 750 mg of soybean-derived
      phosphatidylserine (S-PtdSer), administered daily for 7 d prior to a bout of
      eccentric exercise and for 2d following exercise, on delayed onset of muscle
      soreness and markers of muscle damage, inflammation, and oxidative stress that
      followed prolonged downhill running. METHODS: Following preliminary testing and a
      familiarization session, eight recreationally active males repeated an
      individualized downhill run at -16.5% for 51.0 +/- 1.5 min at 8.7 +/- 0.3 km x h(
      1) on four occasions (trials 1-4). Trials 1 and 37 were presupplementation
      control trials. After trials 1 and 3 the subjects received, in a double-blind and
      crossover fashion, either S-PtdSer or a glucose polymer placebo. Trials 2 and 3
      were separated by a 4-wk washout period. Venous blood, perceived soreness
      ratings, and feeling states were assessed prior to exercise, after exercise, and
      at 24 and 48 h after exercise during each trial. RESULTS: Downhill running led to
      elevations in perceived soreness (P < 0.05), creatine kinase activities (P <
      0.001), myoglobin concentrations (P < 0.001), interleukin-6 (IL-6) concentrations
      (P < 0.001), and lipid hydroperoxide concentrations (P < 0.01). However,
      supplementation did not significantly attenuate these responses. CONCLUSION:
      These results suggest that supplementation with 750 mg x d(-1) S-PtdSer for 10 d
      does not afford additional protection against delayed onset of muscle soreness
      and markers of muscle damage, inflammation, and oxidative stress that follow
      prolonged downhill running.

PMID- 16960524
TI  - Development of novel techniques to classify physical activity mode using
      accelerometers.
AB  - PURPOSE: Use of accelerometers to assess physical activity (PA) is widespread in
      public health research, but their utility is often limited by the accuracy of
      data-processing techniques. We hypothesized that more sophisticated approaches to
      data processing could distinguish between activity types based on accelerometer
      data, providing a more accurate picture of PA. METHODS: Using data from MTI
      Actigraphs worn by six subjects during four activities (walking, walking uphill,
      vacuuming, working at a computer), quadratic discriminant analysis (QDA) was
      performed, and a hidden Markov model (HMM) was trained to recognize the
      activities. The ability of the new analytic techniques to accurately classify PA
      was assessed. RESULTS: The mean (SE) percentage of time points for which the QDA
      correctly identified activity mode was 70.9% (1.2%). Computer work was correctly
      recognized most frequently (mean (SE) percent correct = 100% (0.01%)), followed
      by vacuuming (67.5% (1.5%)), uphill walking (58.2% (3.5%)), and walking (53.6%
      (3.3%)). The mean (SE) percentage of time points for which the HMM correctly
      identified activity mode was 80.8% (0.9%). Vacuuming was correctly recognized
      most frequently (mean (SE) percent correct = 98.8% (0.05%)), followed by computer
      work (97.3% (0.7%)), walking (62.6% (2.3%)), and uphill walking (62.5% (2.3%)).
      In contrast to a traditional method of data processing that misidentified the
      intensity level of 100% of the time spent vacuuming and walking uphill, the QDA
      and HMM approaches correctly estimated the intensity of activity 99% of the time.
      CONCLUSION: The novel approach of estimating activity mode, rather than activity
      level, may allow for more accurate field-based estimates of physical activity
      using accelerometer data, and this approach warrants more study in a larger and
      more diverse population of subjects and activities.

PMID- 16960525
TI  - Effect of fatigue on stroking characteristics in an arms-only 100-m front-crawl
      race.
AB  - PURPOSE: Race analyses during swimming provide information on the time-dependent
      values of, among other variables, a swimmer's clean swimming speed (v), stroke
      rate (SR), and stroke length (SL). The effect of fatigue on changes in v, SR, and
      SL was investigated. METHODS: Lap-averaged values of v, SR, and SL while swimming
      100 m all out with arms only (trial 1) were related to the decline in mechanical
      power output measured during an all-out 100-m swim on the MAD system (trial 2),
      with legs immobilized in both trials. RESULTS: Swimming a 100-m front-crawl
      sprint using arms only led to a significant 24% decrease in lap-averaged
      mechanical power output (from 200 to 153 W, P < 0.01). This reduction in power
      generating capacity led to a 12.4% decrease in v when lap 1 was compared with lap
      4 (from 1.69 to 1.48 m x s(-1), P < 0.01). SR declined throughout the race by
      10.6% from 0.85 Hz (lap 1) to 0.76 Hz (lap 4, P < 0.05). Analysis revealed that
      this decrease in SR was linearly related to the decrease in v. The reduction in
      SR reflected the reduced propulsive force required to overcome the v-dependent,
      and therefore lower, drag. CONCLUSION: Decreases in swimming speed throughout a
      100-m front-crawl race are the result of decreases in the power-producing
      capacity of the swimmer (fatigue). This fatigue-induced reduction in swimming
      speed will lead to a reduction in drag. The SR seems to be accommodated to this
      reduced power output capacity and concomitant diminished propulsion requirements.

PMID- 16960526
TI  - Maximal mechanical power during a taper in elite swimmers.
AB  - INTRODUCTION: Insight regarding the fluctuations in neuromuscular function among
      athletes during a taper is lacking. PURPOSE: This study examined the time course
      of changes in maximal mechanical power (Pmax), torque at power maximum (T),
      velocity at power maximum (V), and swim performance (m x s(-1)) that occur during
      the taper. METHODS: Using an arm ergometer with inertial loading, measurements
      were made during the week prior to the initiation of the taper (high volume, HV),
      during the 2- to 3-wk period of the taper (taper), and during the week of peak
      competition (peak) in 24 male competitive collegiate swimmers. Subjects were
      divided into groups that tapered to peak performance at either the conference
      (CONF, N = 13) or national (NAT, N = 11) championship competitions. RESULTS: CONF
      increased Pmax 10.2% (P < 0.01) and swim performance 4.4% (P < 0.001). NAT
      increased Pmax by 11.6% (P < 0.01), T by 7.4% (P < 0.02), and swim performance by
      4.7% (P < 0.001). Pmax displayed a biphasic increase with approximately 50, 5,
      and 45% of the total increase occurring during the first, second, and third weeks
      of the taper, respectively. The biphasic response was the most common response
      among individual swimmers. Swimming performance was significantly correlated to
      both power and torque (P < 0.05). CONCLUSION: In summary, maximal arm power
      measured using inertial load ergometry increased largely during the first and
      third weeks after training volume was tapered for peak performance in elite
      collegiate swimmers.

PMID- 16960527
TI  - Two percent dehydration impairs and six percent carbohydrate drink improves boys
      basketball skills.
AB  - PURPOSE: To determine the effects of exercise heat-induced two percent
      dehydration (DEH) and euhydration (EUH) with a six percent carbohydrate
      electrolyte solution (CES) compared with placebo EUH (P EUH) on basketball skills
      in skilled young players. METHODS: Fifteen 12- to 15-yr-old boys underwent three
      separate 2-h exercise heat exposures (double blind, random order): 2% DEH by
      limiting fluid intake during exercise in the heat and basketball skill drills,
      EUH (no net weight change) with a 6% CES, and EUH with a flavored water placebo
      (P EUH). After recovery, subjects performed an orchestrated sequence of
      continuous basketball drills designed to simulate a game (12-min quarters + a 10
      min halftime). Performance measures and component drills inherent to basketball
      included various individual and combined shooting percentages (3-point, 15-foot,
      free-throw shots), sprint (suicides, court widths), lateral movement (zigzags,
      lane slides), and defensive drill (combining lateral and front-to-back movement)
      times. RESULTS: Compared with P EUH (53 +/- 11%), combined shooting percentage
      was impaired by 2% DEH (45 +/- 9%; P = 0.002) and improved by CES intake (60 +/-
      8%; P = 0.003). Total sprint times showed a similar effect (83 +/- 10 vs 78 +/- 9
      vs 76 +/- 9 s; DEH vs P EUH vs CES; P < 0.001 and P = 0.04, respectively). Total
      lateral movement times were impaired by 2% DEH (73 +/- 8 vs 68 +/- 8 s; P =
      0.001). CES improved total defensive drill times compared with 2% DEH (77 +/- 10
      vs 82 +/- 10; P = 0.006). CONCLUSION: Deterioration in basketball skill
      performance accompanies two percent dehydration in skilled 12- to 15-yr-old
      basketball players. Additionally, EUH with a 6% CES significantly improves
      shooting performance and on-court sprinting over EUH with water.

PMID- 16960528
TI  - Effect of esophageal acid and prophylactic rabeprazole on performance in runners.
AB  - INTRODUCTION: Acid reflux occurs during exercise. The effects of esophageal acid
      and prophylactic antisecretory treatment on exercise performance are unknown.
      AIMS: To determine 1) the effect of esophageal acid perfusion during exercise on
      pulmonary function and exercise performance, and 2) whether acid suppression with
      rabeprazole (RAB) 20 mg x d(-1) increases exercise performance during esophageal
      acid infusion. METHODS: This was a two-phase study. Twenty-four conditioned
      runners (11 with heartburn, 13 without) completed phase 1. Sixteen runners with
      heartburn completed phase 2 (RAB). For phase 1, esophageal evaluation, baseline
      maximum exertion test, and a standard Bruce protocol maximal stress test were
      performed. Runners were randomized to sham esophageal infusion (NG tube placed in
      the distal esophagus, no fluid) or esophageal acid perfusion (0.1 N HCl perfused)
      during exercise. Subjects were crossed over to the alternate perfusion. For phase
      2, runners underwent three sessions with both acid and sham perfusion during
      running; the sessions were randomly conducted on different days at baseline and 8
      and 12 wk of RAB 20 mg. RESULTS: For phase 1, esophageal function and sensitivity
      were normal. There was no difference in airway resistance or work capacity
      between groups. The acid-perfusion group significantly decreased time to
      exhaustion in the no-heartburn group (23.13 to 20.66 min) with a decrease in
      energy expenditure. For phase 2, time to exhaustion was significantly decreased
      with acid perfusion at all time points (P < 0.05). Total energy expenditure
      during exercise was less in each acid-perfusion test. No difference in pulmonary
      function was present at week 12 versus baseline. CONCLUSIONS: Esophageal acid
      perfusion decreased performance. In runners with heartburn, suppression of
      endogenous acid secretion did not improve exercise performance. Changes in
      cardiopulmonary function do not explain the decreased exercise performance during
      acid perfusion.

PMID- 16960529
TI  - The Yo-Yo IR2 test: physiological response, reliability, and application to elite
      soccer.
AB  - PURPOSE: To examine the physiological response, reliability, and validity of the
      Yo-Yo intermittent recovery level 2 test (Yo-Yo IR2). METHODS: Thirteen normally
      trained male subjects carried out four Yo-Yo IR2 tests, an incremental treadmill
      test (ITT), and various sprint tests. Muscle biopsies and blood samples were
      obtained, and heart rate was measured before, during, and after the Yo-Yo IR2
      test. Additionally, 119 Scandinavian elite soccer players carried out the Yo-Yo
      IR2 test on two to four occasions. RESULTS: Yo-Yo IR2 performance was 591 +/- 43
      (320-920) m or 4.3 (2.6-7.9) min. Test-retest coefficient of variation in
      distance covered was 9.6% (N = 29). Heart rate (HR) at exhaustion was 191 +/- 3
      bpm, or 98 +/- 1% HRmax. Muscle lactate was 41.7 +/- 5.4 and 68.5 +/- 7.6 mmol x
      kg(-1) d.w. at 85 and 100% of exhaustion time, respectively, with corresponding
      muscle CP values of 40.4 +/- 5.2 and 29.4 +/- 4.7 mmol x kg(-1) d.w. Peak blood
      lactate was 13.6 +/- 0.5 mM. Yo-Yo IR2 performance was correlated to ITT
      performance (r = 0.74, P < 0.05) and VO2max (r = 0.56, P < 0.05) but not to 30-
      and 50-m sprint performance. Yo-Yo IR2 performance was better (P < 0.05) for
      international elite soccer players than for moderate elite players (1059 +/- 35
      vs 771 +/- 26 m) and better (P < 0.05) for central defenders (N = 21), fullbacks
      (N = 20), and midfielders (N = 48) than for goalkeepers (N = 6) and attackers (N
      = 24). Fifteen elite soccer players improved (P < 0.05) Yo-Yo IR2 performance by
      42 +/- 8% during 8 wk of preseasonal training. CONCLUSION: This study
      demonstrates that the Yo-Yo IR2 test is reproducible and can be used to evaluate
      an athlete's ability to perform intense intermittent exercise with a high rate of
      aerobic and anaerobic energy turnover. Specifically, the Yo-Yo IR2 test was shown
      to be a sensitive tool to differentiate between intermittent exercise performance
      of soccer players in different seasonal periods and at different competitive
      levels and playing positions.

PMID- 16960530
TI  - Improving the accuracy of pedometer used by the elderly with the FFT algorithm.
AB  - PURPOSE: The aim of this study was to investigate and improve the accuracy of
      accelerometer-type pedometers used by the elderly with slow walking speeds, with
      or without gait disorders, who do or do not use a cane. METHODS: Eighteen
      subjects walked with a cane (5 males, 13 females; age, 80.9 +/- 7.7 yr; height,
      148.1 +/- 7.7 cm; weight, 51.8 +/- 8.8 kg (mean +/- SD); nine had impaired gait),
      and 31 subjects walked without a cane (7 males, 24 females; age, 80.9 +/- 7.7 yr;
      height, 148.1 +/- 7.7 cm; weight, 51.8 +/- 8.8 kg; 15 had impaired gait).
      Subjects walked for approximately 20 m (10 m in each direction and a turning arc)
      at their own speed. We determined the number of steps by pedometer (PM), by
      visually counting the actual number of steps (RM), and by the triaxial
      acceleration signals. The power spectrum of the accelerometer in each direction
      calculated by fast Fourier transform (FFT) for a 4-s temporal window was
      normalized with the maximum power of each window. It was composited, and the
      frequency at maximum power was considered as the cadence. The number of steps
      taken (FM) was determined by summing all the estimated steps in each window.
      RESULTS: PM was significantly less than the RM (P < 0.05), and the error of PM
      was 53.2 +/- 34.1% of RM. FM did not differ from the RM, and the average error of
      FM was -0.7 +/- 7.9% of RM (absolute value: 5.8 +/- 5.3%). CONCLUSION: We suggest
      that our FFT method is suitable for estimating the number of steps during walking
      in this population.

PMID- 16960531
TI  - Neighborhood Environment Walkability Scale: validity and development of a short
      form.
AB  - PURPOSE: The aim of this study was to examine the factorial and criterion
      validity of the Neighborhood Environment Walkability Scale (NEWS) and to develop
      an abbreviated version (NEWS-A). METHODS: A stratified two-stage cluster sample
      design was used to recruit 1286 adults. The sample was drawn from residential
      addresses within eight high- and eight low-walkable neighborhoods matched for
      socioeconomic status. Subjects completed the NEWS and reported weekly minutes of
      walking for transport and recreation using items from the International Physical
      Activity Questionnaire. RESULTS: Multilevel confirmatory factor analysis was used
      to develop measurement models of the NEWS and NEWS-A. Six individual-level and
      five blockgroup-level factors were identified. Factors/scales gauging presence of
      diversity of destinations, residential density, walking infrastructure,
      aesthetics, traffic safety, and crime were positively related to walking for
      transport. Aesthetics, mixed destinations, and residential density were
      associated with walking for recreation. CONCLUSIONS: The NEWS and NEWS-A possess
      adequate levels of factorial and criterion validity. Alternative methods of
      scoring for different purposes are presented.

PMID- 16960533
TI  - A prone positioning protocol for safe patient care: the challenge is to use it.

PMID- 16960534
TI  - Necropsy: the importance of being aware of discrepancies.

PMID- 16960535
TI  - Family presence during cardiopulmonary resuscitation: our anxiety versus their
      needs.

PMID- 16960536
TI  - Interpretation of serum phenytoin concentrations: who would have thought that
      preventing and treating seizures were this challenging?

PMID- 16960537
TI  - Diaphragmatic paralysis after cardiac surgery: how to look at it?

PMID- 16960538
TI  - Testing new drugs for heart failure in children.

PMID- 16960539
TI  - The fundamental role of interfaces in noninvasive positive pressure ventilation.

PMID- 16960540
TI  - Caring for the child with severe traumatic brain injury: old lessons learned and
      new concepts.

PMID- 16960541
TI  - The authors reply: Food for thought.

PMID- 16960543
TI  - Early treatment of acute stress symptoms in pediatric burn patients with
      imipramine and fluoxetine.

PMID- 16960544
TI  - Systemic potassium transport in septic shock.

PMID- 16960546
TI  - Risk factors and prevalence of HIV and sexually transmitted infections among low
      income female commercial sex workers in Mongolia.
AB  - BACKGROUND: Mongolia has very low HIV prevalence despite high rates of sexually
      transmitted infections (STIs). Low-income female sex workers (FSWs) may be at
      high risk for acquiring and spreading the disease in Mongolia. GOAL: The goal of
      this study was to assess the prevalence and risk factors associated with the
      acquisition of HIV, syphilis, gonorrhea, and trichomoniasis among low-income
      female commercial sex workers in 3 urban centers in Mongolia. STUDY DESIGN: One
      hundred seventy-nine low-income FSWs were tested for HIV (enzyme immunoassay) and
      132 were tested for syphilis (Treponema pallidum hemagglutination-confirmed),
      gonorrhea (Gram stain and culture), and trichomoniasis (wet mount microscopy).
      Questionnaires detailing socioeconomic characteristics, sexual behaviors, drug
      and alcohol use, general health, and STI/HIV knowledge were completed by 149
      women. RESULTS: No HIV infections were found in 179 women. Of 132 women, 57
      (43%), 18 (14%), and 37 (28%) tested positive for syphilis, gonorrhea, and
      trichomonas, respectively; 88 (67%) tested positive for one or more STIs and 22
      (17%) were multiply infected. Socioeconomic factors were correlated to reported
      condom use and infection status. CONCLUSIONS: Low-income FSWs in Mongolia
      represent a unique population of very high-risk individuals with very low rates
      of HIV infection. Interventions targeting this population represent a unique
      opportunity to prevent a potentially rapid increase of HIV infection in urban
      Mongolia.

PMID- 16960547
TI  - A comparison of one year of episodic or suppressive treatment of recurrent
      genital herpes with valacyclovir.
AB  - OBJECTIVES: We conducted this study to compare episodic and suppressive therapy
      for genital herpes about disease characteristics, disease burden, and psychologic
      impact. STUDY DESIGN: The authors conducted a randomized, open-label, 1-year
      treatment trial. RESULTS: Forty subjects were randomized to episodic therapy with
      valacyclovir (500 mg twice daily for 5 days) and 40 to suppressive therapy (500
      mg daily). Subjects in the episodic arm experienced more outbreaks (7.87 +/-
      4.65) than those in the suppressive arm (1.59 +/- 1.93) (P <0.001). Subjects in
      the episodic arm also had significantly more days with pain and lesions (6.5 +/-
      7.3) than those in the suppressive arm (1.1 +/- 3.3) (P < 0.001), and other
      quantitative measures of disease burden also favored the suppressive arm. Both
      treatment groups had significant improvements in their recurrent genital herpes
      quality-of-life scores from baseline that persisted throughout the study;
      however, there was no significant difference between the treatment arms in these
      scores. CONCLUSIONS: Suppressive therapy of recurrent genital herpes with
      valacyclovir has a greater impact on measures of disease frequency and burden
      than episodic therapy. However, both treatment strategies lead to significant
      improvements in recurrent genital herpes quality-of-life scores. Both treatment
      strategies benefit patients with recurrent genital herpes.

PMID- 16960548
TI  - How do we interpret the HIV incidence estimates reported by Kumwenda et al?

PMID- 16960549
TI  - Evaluation of a fruit and vegetable distribution program--Mississippi, 2004-05
      school year.
AB  - Although diets high in fruit and vegetables are associated with decreased risk
      for many chronic diseases, consumption of fruit and vegetables among children is
      below recommended levels. During the 2004-05 school year, the Mississippi
      Department of Education Child Nutrition Program initiated the Mississippi Fresh
      Fruit and Vegetable Pilot Program. The program was designed to 1) increase
      student access to fresh fruit and vegetables, 2) increase the degree of student
      preference for fruit and vegetables, and 3) increase fruit and vegetable
      consumption. The 25 schools selected to participate in the program distributed
      fresh fruit and vegetables free of charge during the school day and provided
      nutrition education activities to promote and support consumption of fruit and
      vegetables. An evaluation of the program was conducted using a pretest in the
      fall (before the program was implemented by the schools) and a posttest in the
      spring (at the end of the school year). This report summarizes the findings of
      that evaluation, which indicated that the program might have 1) increased the
      variety of fruit and vegetables ever tried by students from all three grades
      sampled (5th, 8th, and 10th); 2) increased the degree of preference for fruit
      among 8th-grade and 10th-grade students; 3) promoted positive attitudes toward
      eating fruit among 8th-grade students; 4) increased consumption of fruit, but not
      vegetables, among 8th-grade and 10th-grade students; and 5) decreased preference
      for fruit and vegetables, the belief that they could eat more vegetables, and
      willingness to try new fruit and vegetables among 5th-grade students. The results
      of this evaluation suggest that the distribution of fresh fruit at school free of
      charge to secondary school students might be an effective component of a
      comprehensive approach for improving student dietary behaviors; however,
      distribution of fresh vegetables might be more effective with changes in program
      implementation.

PMID- 16960550
TI  - Update: Delayed onset Pseudomonas fluorescens bloodstream infections after
      exposure to contaminated heparin flush--Michigan and South Dakota, 2005-2006.
AB  - In March 2005, CDC reported a multistate outbreak of Pseudomonas fluorescens
      bloodstream infections associated with use of syringes preloaded with heparin
      intravenous catheter flush. The heparin flush became contaminated during
      preparation by IV Flush, LLC (Rowlett, Texas). Thirty-six patients in four states
      were identified who had been exposed to the contaminated flush and subsequently
      experienced P. fluorescens bloodstream infection during December 2004-February
      2005. Based on a recommendation by the Food and Drug Administration (FDA), IV
      Flush voluntarily recalled the preloaded syringes in late January; on January 31
      and February 4, 2005, FDA issued nationwide alerts recommending that consumers
      and institutions stop using and return the preloaded syringes to IV Flush or the
      distributor (Pinnacle Medical Supply, Rowlett, Texas). Approximately 3 months
      after the product was recalled, patients in Michigan and South Dakota were
      identified with P. fluorescens bloodstream infections. As of April 2006, a total
      of 15 patients in Michigan and 13 in South Dakota had been identified with
      delayed onset P. fluorescens bloodstream infections, with occurrences ranging
      from 84 to 421 days after their last potential exposure to the contaminated
      flush. The patients all had indwelling central venous catheters and received
      treatment during October 2005-February 2006 at clinics known to have used the
      contaminated flush. This report describes the investigation of these cases, which
      determined that these were delayed onset cases of P. fluorescens bloodstream
      infection from a past exposure to contaminated flush, and provides
      recommendations for ongoing surveillance for delayed P. fluorescens bloodstream
      infections among similarly exposed patients.

PMID- 16960551
TI  - Measles outbreak and response--Fiji, February-May 2006.
AB  - In September 2005, the 37 countries and areas of the World Health Organization
      (WHO) Western Pacific Region (WPR) established a goal to eliminate measles in the
      region by 2012. After multiple outbreaks in 1996 and 1997, measles supplementary
      immunization activities (SIAs) in 1997 and 1998 resulted in apparent interruption
      of measles transmission in WPR. Since then, importations have resulted in limited
      outbreaks in French Polynesia and Guam, a large outbreak in the Marshall Islands
      in 2003, and an outbreak in Fiji during February-May 2006. This report describes
      the epidemiologic findings, public health response, and potential causes of the
      2006 outbreak that produced 132 measles cases in Fiji (2006 estimated population:
      832,432), the most populous country in the South Pacific.

PMID- 16960552
TI  - Locally acquired mosquito-transmitted malaria: a guide for investigations in the
      United States.
AB  - Recent outbreaks of locally acquired mosquito-transmitted malaria in the United
      States demonstrate the continued risk for reintroduction of the disease. Since
      1957, when CDC's Malaria Branch started conducting malaria surveillance, 63
      outbreaks have occurred, constituting 156 cases (annual range: 1-32) that were a
      result of locally acquired mosquitoborne transmission. This report describes the
      steps that should be taken to 1) investigate a case that might have been acquired
      locally, 2) prevent a small focus of malaria cases from becoming a source of
      sustained transmission, and 3) inform clinicians regarding the process of an
      investigation so they can effectively address concerns and questions from
      patients. Although these locally acquired mosquito-transmitted outbreaks
      frequently involve only a limited number of infected persons, they frequently
      raise concerns in the community and require substantial public health resources.
      For example, as a result of the most recent local outbreak of eight malaria cases
      in Florida in 2003, reverse 911 telephone calls (a community notification system)
      were made to approximately 300,000 residents; insect repellent, postcards,
      flyers, and posters in multiple languages were distributed; public announcements
      were made through the media and to schools and homeless shelters; and
      notifications were sent to local hospitals and physicians to inform residents of
      that community. When a local health department investigates a potential locally
      acquired mosquito-transmitted case, the systematic inquiry should include
      epidemiologic, environmental, and laboratory components. Local and state health
      departments inquiring about the proper approach to investigate and control a
      potential locally acquired case frequently request urgent assistance and tools
      from CDC. This report provides a starting point for such investigations to local
      and state health departments by providing them with the tools necessary to
      initiate an investigation.

PMID- 16960553
TI  - Select cancer testes antigens of the MAGE-A, -B, and -C families are expressed in
      mast cell lines and promote cell viability in vitro and in vivo.
AB  - MAGE antigens are proteins that are normally expressed only in gametes but are
      often aberrantly expressed in melanomas, hematopoietic malignancies, and other
      "cancers". The functions of most MAGE proteins are unknown. Data have accumulated
      suggesting expression of MAGE proteins by malignant cells may contribute to
      advanced disease or resistance to chemotherapy, but direct evidence supporting
      this hypothesis is lacking. We show here that small interfering RNA (siRNA)
      suppression of MAGE-A, -B, and -C gene expression slows proliferation and induces
      caspase independent apoptosis in human and murine mast cell lines. Furthermore,
      treatment with MAGE specific siRNA suppresses growth of malignant cells in an in
      vivo murine model of mastocytosis. These observations demonstrate that MAGE
      protein expression can contribute to the development of tumors by permitting
      proliferation and prolonging the survival of malignant cells. We suggest a shift
      of the current clinical paradigm from one that envisions MAGE proteins solely as
      targets for immunologic attack to one in which MAGE genes and proteins are also
      targets for functional manipulation.

PMID- 16960554
TI  - Recombinant measles virus induces cytolysis of cutaneous T-cell lymphoma in vitro
      and in vivo.
AB  - Measles virus (MV) has shown promise as an oncolytic virus in the treatment of
      different tumor models for human B-cell lymphoma, multiple myeloma, ovarian
      cancer, and glioma. We have shown that, in a phase I clinical trial, MV vaccine
      induces tumor regression in cutaneous T-cell lymphoma (CTCL) patients. Here, we
      investigated in detail, the effect of recombinant MV (rMV) vaccine strain in CTCL
      cell cultures, and in vivo in established CTCL xenografts in nude mice. The
      susceptibility of three CTCL cell lines, originating from patients, to rMV was
      tested by determination of cell surface expression of MV receptors. All cell
      lines expressed the receptors CD150 and CD46 and were easily infected by rMV and
      induced complete cell lysis. The cytoreductive activity was apparent in cells
      forming aggregates, indicating a cell-to-cell spread of MV and cytolysis owing to
      virus infection. Intratumoral (i.t.) injection of rMV, expressing enhanced green
      fluorescent protein induced complete regression of large established human CTCL
      tumors in nude mice, whereas tumors with control treatment progressed
      exponentially. Immunohistochemical analysis of tumor biopsies, after i.t.
      treatment, for MV-NP protein complex demonstrated replication of MV within the
      tumors. The data demonstrate the potential of MV as a therapeutic agent against
      CTCL.

PMID- 16960555
TI  - Tumor-derived fibronectin is involved in melanoma cell invasion and regulated by
      V600E B-Raf signaling pathway.
AB  - Melanomas are malignant tumors of melanocytes that, if not detected early, are
      highly aggressive and poorly treatable. Activation of extracellular signal
      regulated (ERK)/mitogen-activated protein (MAP) kinase signaling is commonly
      found in melanomas mainly through oncogenic mutations of B-Raf. We previously
      reported that activation of ERK/MAP kinase stimulates synthesis of fibronectin by
      upregulating the transcription factor early growth response-1 (Egr-1). To further
      analyze the link between ERK/MAP kinase pathway and fibronectin in melanoma, we
      have studied the regulation and role of fibronectin produced by melanoma cells
      bearing oncogenic B-Raf mutation. We show that fibronectin is expressed in situ
      during tumor progression and that high fibronectin and Egr-1 levels are found in
      cells expressing this mutation. Expression of active mutants of B-Raf induces
      fibronectin, whereas endogenous fibronectin is inhibited by small interfering RNA
      (siRNA)-mediated depletion of B-Raf or Egr-1. In contrast, stimulation of ERK
      pathway is insufficient to promote fibronectin upregulation in normal
      melanocytes. Finally, we show that suppression of fibronectin by siRNA leads to
      decreased melanoma cell invasiveness in vitro. These results reveal a tumor
      specific regulation of fibronectin by constitutive ERK/MAP kinase signaling and
      indicate that self-production of fibronectin may play a role in melanoma
      tumorigenesis, by promoting tumor cell invasion.

PMID- 16960556
TI  - Dealing with disclosure.
AB  - Researchers' disclosures of competing financial interests are undergoing a
      dangerous transformation from instruments of transparency to evidence of
      wrongdoing.

PMID- 16960557
TI  - AIDS meeting spotlights pills to prevent infection.

PMID- 16960558
TI  - University shuts down virologist's work on questionable AIDS drug.

PMID- 16960559
TI  - Mysterious 'Morgellons disease' prompts US investigation.

PMID- 16960560
TI  - Text messages dig up pure water for Bangladesh's poor.

PMID- 16960561
TI  - Drug companies accused of stalling tailored therapies.

PMID- 16960563
TI  - A few good scientists.

PMID- 16960564
TI  - Profile: Paul Epstein.

PMID- 16960566
TI  - Killers become builders during pregnancy.

PMID- 16960567
TI  - Taming the clot-buster tPA.

PMID- 16960568
TI  - Microbes adapt to inner space.

PMID- 16960569
TI  - Hypoxia pathway linked to kidney failure.

PMID- 16960570
TI  - HDAC7 supports vascular integrity.

PMID- 16960571
TI  - Snake bites and bee stings: the mast cell strikes back.

PMID- 16960572
TI  - Supressing the supressors.

PMID- 16960573
TI  - Enabling the suppressors.

PMID- 16960575
TI  - Inflammation in Alzheimer disease: driving force, bystander or beneficial
      response?
AB  - Alzheimer disease is a progressive dementia with unknown etiology that affects a
      growing number of the aging population. Increased expression of inflammatory
      mediators in postmortem brains of people with Alzheimer disease has been
      reported, and epidemiological studies link the use of anti-inflammatory drugs
      with reduced risk for the disorder. On the initial basis of this kind of
      evidence, inflammation has been proposed as a possible cause or driving force of
      Alzheimer disease. If true, this could have important implications for the
      development of new treatments. Alternatively, inflammation could simply be a
      byproduct of the disease process and may not substantially alter its course. Or
      components of the inflammatory response might even be beneficial and slow the
      disease. To address these possibilities, we need to determine whether
      inflammation in Alzheimer disease is an early event, whether it is genetically
      linked with the disease and whether manipulation of inflammatory pathways changes
      the course of the pathology. Although there is still little evidence that
      inflammation triggers or promotes Alzheimer disease, increasing evidence from
      mouse models suggests that certain inflammatory mediators are potent drivers of
      the disease. Related factors, on the other hand, elicit beneficial responses and
      can reduce disease.

PMID- 16960576
TI  - Pathophysiologically based treatment interventions in schizophrenia.
AB  - Identifying the molecular alterations that underlie the pathophysiology of
      critical clinical features of schizophrenia is an essential step in the rational
      development of new therapeutic interventions for this devastating illness.
      Cognitive deficits, such as the impairments in working memory that arise from
      dysfunction of the dorsolateral prefrontal cortex, are a major determinant of
      functional outcome in schizophrenia. Here we consider the contributions of
      disturbances in glutamate, dopamine and GABA neurotransmission to the
      pathophysiology of working memory impairments in schizophrenia, suggest a cascade
      of molecular events that might link these disturbances, and argue that the
      molecular alterations most proximal to the pathophysiology of prefrontal
      dysfunction offer the most promise as targets for new drug development.

PMID- 16960577
TI  - The autoimmune regulator (Aire) controls iNKT cell development and maturation.

PMID- 16960580
TI  - Outside the ivory tower.

PMID- 16960581
TI  - Jaw centre.

PMID- 16960582
TI  - Slumbering time-bomb.

PMID- 16960583
TI  - Unfair accusations.

PMID- 16960584
TI  - Eastman excitement.

PMID- 16960585
TI  - Positive control.

PMID- 16960586
TI  - 'X' shaped incisor.

PMID- 16960587
TI  - An expert witness.

PMID- 16960588
TI  - Future training needs.

PMID- 16960589
TI  - Sincere concerns.

PMID- 16960590
TI  - Dental letters.

PMID- 16960591
TI  - Grass roots observation.

PMID- 16960592
TI  - Arresting caries.

PMID- 16960607
TI  - Treatment planning of the edentulous maxilla.
AB  - The predictability of successful osseointegrated implant rehabilitation of the
      edentulous jaw as described by Branemark et al., introduced a new era of
      management for the edentulous predicament. Implant rehabilitation of the
      edentulous maxilla remains one of the most complex restorative challenges because
      of the number of variables that affect both the aesthetic and functional aspect
      of the prosthesis. Among the prosthesis designs used to treat the edentulous
      maxilla are fixed or removable implant-supported restorations. Since the
      aesthetic requirements and preoperative situation of each patient varies,
      considerable time must be spent on accurate diagnosis to ensure patient desires
      are satisfied and predictable outcomes are achieved. The purpose of this article
      is to compare the treatment options and prosthesis designs for the edentulous
      maxilla. Emphasis will be placed on diagnosis and treatment planning. Criteria
      will be given to guide the practitioner in deciding whether a fixed or removable
      restoration should be placed. This objective will be accomplished through the
      review of cases with regard to varying design considerations and factors that
      influence the decision-making process.

PMID- 16960608
TI  - Loss of a clinical attachment level in a child: differential diagnosis with
      aggressive periodontitis. Case report.
AB  - A nine-year-old boy presented with a serious periodontal lesion caused by a
      rubber band that had been used to close a medial diastema. Surgery was required
      to remove it. The impaction of a foreign body in the periodontal space should be
      suspected when a clinical attachment level is lost during childhood.

PMID- 16960615
TI  - The knowledge of healthcare professionals regarding elderly persons' oral care.
AB  - OBJECTIVE: The aim of this study was to compare the knowledge and views of
      nursing staff on both acute elderly care and rehabilitation wards regarding
      elderly persons' oral care with that of carers in nursing homes. SUBJECTS: One
      hundred nurses working on acute, sub-acute and rehabilitation wards for elderly
      people (Group 1) and 75 carers in nursing homes (Group 2) were surveyed. DESIGN:
      A semi-structured questionnaire. RESULTS: Similar percentages of each group of
      nurses were registered with a dentist (86% and 88% respectively), although more
      hospital-based nurses were anxious about dental treatment compared with the
      nursing home group (40% and 28% respectively). More carers in nursing homes gave
      regular advice about oral care than the hospital-based nurses (54% and 43%
      respectively). Eighteen per cent of each group thought that edentulous
      individuals did not require regular oral care. Eighty-five per cent of hospital
      based nurses and 95% of nursing home carers incorrectly thought that dentures
      were 'free' on the NHS. Although trends were observed between the two groups, no
      comparisons were statistically significant (Chi-square; level p < 0.05).
      CONCLUSIONS: Deficiencies exist in the knowledge of health care workers both in
      hospital and in the community setting, although the latter were less
      knowledgeable but more likely to give advice to older people.

PMID- 16960616
TI  - Nosocomial transmission of methicillin-resistant Staphylococcus aureus via the
      surfaces of the dental operatory.
AB  - OBJECTIVE: We assess the possibility of methicillin-resistant Staphylococcus
      aureus (MRSA) transmission via the surfaces of the dental operatory. METHODS: A
      survey of MRSA contamination on the surfaces of the dental operatory, and an
      analysis of MRSA transmission via the dental operatory between patients was
      carried out in the department of special dental care and oral surgery. RESULTS:
      MRSA was observed on the surfaces of dental operatory including the air-water
      syringe and reclining chair. Nosocomial infection or colonisation of MRSA
      occurred in eight out of 140 consecutive patients who had no evidence of MRSA at
      admission. Antibiograms of 30 antibiotics revealed that the isolates from the
      eight patients were of the same strain as those from the surface of dental
      operatory. After treating the patients under a revised infection control (IC)
      protocol including a single use of barrier covers, MRSA was not detected on the
      surfaces of the dental operatory, and no nosocomial infection or colonisation
      occurred during hospitalisation (0/117 patients). CONCLUSIONS: These results
      suggest that MRSA contaminates the surfaces of the dental operatory, and
      therefore the dental operatory should be considered a possible reservoir of MRSA.

PMID- 16960632
TI  - Children's self-reports of pain intensity: scale selection, limitations and
      interpretation.
AB  - Most children aged five years and older can provide meaningful self-reports of
      pain intensity if they are provided with age-appropriate tools and training. Self
      reports of pain intensity are an oversimplification of the complexity of the
      experience of pain, but one that is necessary to evaluate and titrate pain
      relieving treatments. There are many sources of bias and error in self-reports of
      pain, so ratings need to be interpreted in light of information from other
      sources such as direct observation of behaviour, knowledge of the circumstances
      of the pain and parents' reports. The pain intensity scales most commonly used
      with children - faces scales, numerical rating scales, visual analogue scales and
      others - are briefly introduced. The selection, limitations and interpretation of
      self-report scales are discussed.

PMID- 16960633
TI  - Ensuring pain relief for children at the end of life.
AB  - Pain management in the context of pediatric palliative care can be challenging.
      The present article reviews, through a case-based presentation, the
      nonpharmacological and pharmacological methods used to ensure adequate pain
      control in children facing end of life. Details on the impressive range of opioid
      dosages required and routes of administration are highlighted from published
      literature and clinical experience. Where available, evidence-based
      recommendations are provided. Potential side effects of pain medication and
      barriers to good pain control are discussed. Novel analgesics and innovative
      delivery methods are presented as future tools enhancing pain relief at the end
      of life. Some challenges to ethically grounded research in this important context
      of care are reviewed.

PMID- 16960634
TI  - Innovative approaches to neuraxial blockade in children: the introduction of
      epidural nerve root stimulation and ultrasound guidance for epidural catheter
      placement.
AB  - Continuous epidural blockade remains the cornerstone of pediatric regional
      anesthesia. However, the risk of catastrophic trauma to the spinal cord when
      inserting direct thoracic and high lumbar epidural needles in anesthetized or
      heavily sedated pediatric patients is a concern. To reduce this risk, research
      has focused on low lumbar or caudal blocks (ie, avoiding the spinal cord) and
      threading catheters from distal puncture sites in a cephalad direction. However,
      with conventional epidural techniques, including loss-of-resistance for
      localization of the needle, optimal catheter tip placement is difficult to assess
      because considerable distances are required during threading. Novel approaches
      include electrical epidural stimulation for physiological confirmation and
      segmental localization of epidural catheters, and ultrasound guidance for
      assessing related neuroanatomy and real-time observation of the needle puncture
      and, potentially, catheter advancement. The present article provides a brief and
      focused review of these two advances, and outlines recent clinical experiences
      relevant to pediatric epidural anesthesia.

PMID- 16960635
TI  - A survey of the pain experienced by males and females with Fabry disease.
AB  - BACKGROUND: The clinical onset of Fabry disease, a rare, X-linked, multisystemic
      disorder, is marked by neuropathic pain. Males suffer extensively from this
      disease. Females, as genetic 'carriers', have traditionally been viewed as either
      asymptomatic or mildly afflicted with this disease. OBJECTIVES: To describe Fabry
      related pain and compare experiences between the sexes. Patients' perceptions of
      physician pain assessments were also examined. METHODS: A disease-specific
      questionnaire was accessible on-line (www.fabry.org) and mailed to 552 members of
      a Fabry disease support group. RESULTS: The response rate was 14.3% for the
      support group-based mail questionnaire. Females (58.0%) were significantly older
      (mean +/- SD 45.9+/-13.5 years) than males (mean +/- SD 40.0+/-12.1; t [86]=
      2.11, P<0.05). Females were diagnosed with Fabry disease later (31.1+/-14.0
      years) than males (24.2+/-11.9 years; t [86]=-2.43, P<0.05). Females (mean score
      for pain disability rating 3.0+/-1.4) suffered more extensive disability from
      migraine pain (mean score 2.2+/-1.3; F [1, 74]=45.0, P<0.005), and, unlike males,
      did not exhibit a decline in pain intensity with disease duration. Satisfaction
      with physician pain assessments was moderate. CONCLUSIONS: Contrary to the
      traditional view of females as carriers, females with Fabry disease experienced
      intense disease-related pain; pain produced comparable distress and impairment in
      both sexes. The diagnostic delay and absence of a decline in pain symptoms over
      time in females suggest additional disease burden. Females may be triply
      disadvantaged in the health care system due to disease rarity, devalued carrier
      status and sex.

PMID- 16960636
TI  - Infrared therapy for chronic low back pain: a randomized, controlled trial.
AB  - OBJECTIVE: The objective of the present study was to assess the degree of pain
      relief obtained by applying infrared (IR) energy to the low back in patients with
      chronic, intractable low back pain. METHODS: Forty patients with chronic low back
      pain of over six years' duration were recruited from patients attending the
      Rothbart Pain Management Clinic, North York, Ontario. They came from the patient
      lists of three physicians at the clinic, and were randomly assigned to IR therapy
      or placebo treatment. One patient dropped out of the placebo group; as a result,
      21 patients received IR therapy and 18 received placebo therapy. The IR therapy
      was provided by two small, portable units in a sturdy waistband powered by small,
      rechargeable batteries made by MSCT Infrared Wraps Inc (Canada). These units met
      safety standards for Food and Drug Administration portability, and are registered
      with the Food and Drug Administration as a therapeutic device. The unit converted
      electricity to IR energy at 800 nm to 1200 nm wavelength. The treated group
      received IR therapy. The placebo group had identical units, but the power was not
      connected to the circuit-board within the IR pad. Patients attended seven weekly
      sessions. One baseline and six weekly sets of values were recorded. The principle
      measure of outcome was pain rated on the numerical rating scale (NRS). The pain
      was assessed overall, then rotating and bending in different directions. RESULTS:
      The mean NRS scores in the treatment group fell from 6.9 of 10 to 3 of 10 at the
      end of the study. The mean NRS in the placebo group fell from 7.4 of 10 to 6 of
      10. CONCLUSION: The IR therapy unit used was demonstrated to be effective in
      reducing chronic low back pain, and no adverse effects were observed.

PMID- 16960637
TI  - Whiplash injuries can be visible by functional magnetic resonance imaging.
AB  - Whiplash trauma can result in injuries that are difficult to diagnose. Diagnosis
      is particularly difficult in injuries to the upper segments of the cervical spine
      (craniocervical joint [CCJ] complex). Studies indicate that injuries in that
      region may be responsible for the cervicoencephalic syndrome, as evidenced by
      headache, balance problems, vertigo, dizziness, eye problems, tinnitus, poor
      concentration, sensitivity to light and pronounced fatigue. Consequently,
      diagnosis of lesions in the CCJ region is important. Functional magnetic
      resonance imaging is a radiological technique that can visualize injuries of the
      ligaments and the joint capsules, and accompanying pathological movement
      patterns. Three severely injured patients that had been extensively examined
      without any findings of structural lesions were diagnosed by functional magnetic
      resonance imaging to have injuries in the CCJ region. These injuries were
      confirmed at surgery, and after surgical stabilization the medical condition was
      highly improved. It is important to draw attention to the urgent need to diagnose
      lesions and dysfunction in the CCJ complex and also improve diagnostic methods.

PMID- 16960638
TI  - The prevalence of and variables associated with smoking in children and
      adolescents.
AB  - OBJECTIVE: To identify the prevalence of smoking and the presence of variables
      associated with the habit in children and adolescents of both sexes, aged 7 to 17
      years, resident in the city of Maceio. METHODS: A cross-sectional epidemiological
      study of the student population of the both private and public education systems
      at elementary and high school level. Sample size was calculated based on the
      minimum predicted prevalence of a large number of variables, including smoking
      itself. Cluster sampling was employed. A questionnaire on smoking habits was
      completed during individual interviews with each student. Children who admitted
      having smoked on 1 or more day during the previous 30 were defined as current
      smokers. The variables analyzed were related to: the students (age, sex, previous
      experimentation with cigarettes and paid employment), their educational status
      (public/private school, daytime/evening lessons, grade and repeated years) and
      their families (economic status, smoking parents and separated parents). RESULTS:
      A total of 1,253 students were analyzed (547 were male, mean age was 12.4+/-2.9
      years). Observed smoking prevalence was 2.4%. Multivariate statistical analysis
      demonstrated significant associations between smoking and: increased age (odds
      ratio: 1.31); previous experimentation with cigarettes (odds ratio: 33.96);
      studying during the evening (odds ratio: 5.43). It was observed that 286 students
      (22.8%) admitted having experimented with cigarettes (9% from 7 to 9 years; 21%
      from 10 to 14 years; 36% from 15 to 17 years). CONCLUSIONS: The prevalence of
      smoking among children and adolescents in the Maceio educational system is 2.4%,
      being most common among students aged 15 to 17 years, studying in the evening.
      Students who had experimented with cigarettes exhibited a 34 times greater chance
      of becoming smokers.

PMID- 16960639
TI  - Variability in the establishment of an external reference point for central
      venous pressure measurement in children.
AB  - OBJECTIVE: To investigate the variability in the establishment of the midaxillary
      line as external reference point (ERP), by different healthcare workers, for the
      measurement of central venous pressure in children. METHODS: Descriptive and
      correlational study carried out in a pediatric intensive care unit of a teaching
      hospital. During the establishment of the midaxillary line as ERP for central
      venous pressure measurement, five assessments of the same patient made by
      healthcare workers and one assessment made by a trained evaluator were compared.
      A total of 120 assessments were made by 44 healthcare workers, 17 (38.6%) by
      nursing assistants and nursing technicians, 16 (36.3%) by nurses and 11 (25.1%)
      by physicians, in addition to 24 assessments made by the trained evaluator. The
      data were analyzed using the chi-square test, ANOVA, Kruskal-Wallis test and t
      test. Significance level was set at 5%. RESULTS: There was statistically
      significant difference between the assessments made by healthcare workers and by
      the evaluator (p < 0.001). The comparison of the variability in the measurements
      made by healthcare workers revealed that 56 (46.7%) measurements were lower than
      those obtained by the evaluator (range from -0.5 to -9), 44 (36.7%) were higher
      (range from 0.5 to 4) and 20 (16.7%) were concordant (zero variability).
      Professional category did not influence the concordance between the ERPs (p =
      0.899), or the variability observed (p = 0.778). However, the measurements made
      by professionals with greater experience in intensive care tended to differ more
      sharply from those made by the evaluators. CONCLUSION: The indications of the
      midaxillary line as ERP presented variations when measured by the healthcare team
      and by the trained evaluator. Variability was not influenced by professional
      category, and the more experienced the healthcare worker, the greater the
      probability for underestimation of the ERP. According to the results of this
      study, such situations may compromise both the efficacy of this procedure and
      patient safety.

PMID- 16960640
TI  - Evaluation of peak inspiratory pressure and respiratory rate during ventilation
      of an infant lung model with a self-inflating bag.
AB  - OBJECTIVE: To evaluate the peak inspiratory pressure and ventilation rate
      achieved by physicians when using a neonatal self-inflating bag on a lung model.
      METHODS: Fifteen physicians ventilated full term and preterm infant lung
      simulators while the outcomes were captured by a ventilation monitor. RESULTS:
      Median peak pressures in cmH(2)O for full term and preterm lungs were 23
      (interquartile range: 15-47) and 26 (interquartile range: 14-51), being less than
      20 in 41.2 and 35.8% of the pressure curves analyzed, more than 40 in 29.7 and
      33.6%, and between 27 and 33 cmH(2)O in 8.2 and 6.5% of the curves, respectively.
      Median ventilation rates were 45 (interquartile range: 36-57) and 48
      (interquartile range: 39-55.5) cycles per minute, being more than 30 in 9.3 and
      6.7% of pressure curves and more than 60 in 12 and 13.3% of pressure curves, for
      the full term and preterm lungs, respectively. The differences between these
      medians were not statistically significant. CONCLUSIONS: Ventilation rates
      achieved with the self-inflating bag were adequate in approximately 80% of
      pressure curves analyzed, but the physicians were unable to provide ventilation
      with minimal pressure variation, producing pressures that diverged from those
      defined by the neonatal resuscitation training course in 70% of the curves. This
      was irrespective of whether they were ventilating the lung model analogous to
      preterm or full term infant lungs.

PMID- 16960641
TI  - [Ophthalmic artery aneurysms].
AB  - INTRODUCTION: Ophthalmic artery aneurysms are infrequent lesions and they have
      very specific particularities. OBJECTIVE: to present the anatomoclinical and
      surgical characteristic of our patients with ophthalmic aneurysms and to analyze
      our surgical results. PATIENT AND METHODS: 604 patients with intracranial
      aneurysms were operated on between January 1982 and December 2004. There were 50
      patients with ophthalmic artery aneurysms. Average age was 52 years, 80% were
      women, 60% harbored multiple aneurysms and 20% were giant lesions. 12% had
      bilateral ophthalmic aneurysms. 20% of ophthalmic aneurysms were incidental. 50%
      had ophthalmological manifestations; however, this presentation occurred in 100%
      of the patients with large and giant aneurysms. Initially, 12% of ophthalmologic
      disorders were missed. We utilized unilateral or bilateral pterional approach
      associated to others in multiple aneurysms. We performed retrograde decompression
      suction technique modified for large and giant aneurysms. RESULTS. Thirty
      patients (60%) obtained a complete recovery, fourteen patients (28%) an
      incomplete recovery and two were seriously disabled. There were not patients in
      vegetative state. There were four deaths (8%). 50% of postoperatory deficits
      disappeared and 64% of ophthalmologic disorders improved three months later.
      CONCLUSION: Microsurgical method allowed to treat unique, multiple, bilateral,
      large and giant ophthalmic aneurysms with good recovery of neurological and
      visual deficits.

PMID- 16960642
TI  - [Intracranial arteriovenous malformations and radiosurgery with LINAC: review
      article].
AB  - Among all vascular malformations, the intracranial arteriovenous malformations
      (AVM's) have the most powerful impact from the clinical point of view. The
      manifestations include hemorrhage, seizures, headacheh, but sometimes they are
      incidentally found during the diagnostic approach of patients with head trauma or
      chronic headache. There are three different types of treatments: microsurgery,
      endovascular treatment and radiosurgery. The actual role of the endovascular
      treatment is as an adjuvant therapy before microsurgery or radiosurgery just to
      diminish the nidus size. The goal of all treatments is complete nidus
      obliteration without causing a new neurological deficit. The overall obliteration
      index with LINAC based radiosurgery is about 80% and the result is dose, volume
      and time dependent. The mean dose reported in the literature fluctuates between
      15 and 25 Gy, and the isodose coverage curve for the AVM with LINAC is generally
      the one of the 80%. There can be a treatment failure defined as the necessity to
      retreat the patient after three years from the first radiosurgical treatment in
      about 26% of the patients. There is a lack of evidence, principally from
      randomized trials, to point out the role of each of the modalities in the
      treatment of the AVM.

PMID- 16960643
TI  - [Quality of life in intracranial aneurysm: surgery versus endovascular
      treatment].
AB  - BACKGROUND: Based on earlier studies, we aimed to determine the quality of life
      of patients with intracranial aneurysm after their treatment by surgery or
      embolization and to compare the quality of life of these two groups. METHODS: The
      SF-36 health questionnaire was retrospectively applied to 93 patients with
      intracranial aneurysm treated with surgery (n=56) or embolization (n=37).
      RESULTS: The quality of life of some patients was impaired but 50% of patients
      treated with surgery and 40.5% of patients treated with embolization showed no
      impairment in any SF-36 domain. The quality of life in the Physical Functioning
      domain was higher in embolization-treated than in surgery-treated patients.
      CONCLUSIONS: Some patients with intracranial aneurysms treated with surgery or
      endovascular embolization have an impaired quality of life. Endovascular
      treatment may cause less limitation in physical function. The quality of life of
      these patients is affected by numerous factors, in addition to the type of
      treatment.

PMID- 16960644
TI  - [Calcified disc herniation in childhood].
AB  - Calcification of intervertebral discs is a rare occurrence in children. Although
      the etiology of the calcification remains uncertain, it is no related with
      degenerative diseases. The clinical picture is non specific with neck pain,
      muscle contractures and, sometimes, low-grade fever. These symptoms generally
      disappear spontaneously, and surgery rarely becomes necessary. In our review of
      the literature, we have found only seventeen cases requiring surgical management.
      Two of these children had been previously diagnosed with calcified intervertebral
      discs, but at the time no herniation had been ruled out with magnetic resonance
      imaging (MRI). We report the case of a girl who was diagnosed, when she was ten
      years old, with intervertebral idiopatic calcifications. Four years later she
      presented with radiculopathy caused by the posterolateral displacement of a
      calcified cervical disc, which required operative management. We think that this
      case supports the theory of Heinrich et al. that considers that the calcified
      hernia is a complication of a previous pathology, namely intervertebral
      calcification. Clinical and therapeutic aspects of this entity are discussed.

PMID- 16960645
TI  - [Familiar glioblastoma presenting as a true multicentric tumor: etiopathogenic
      and prognostic features].
AB  - Familial glioblastoma multiforme is a rather uncommon entity, being in most cases
      associated to known genetic disorders (as Turcot syndrome, Li-Fraumeni syndrome,
      neurofibromatosis, etc.). However, familial gliomas have also been described,
      although less frequently, independently of these genetic syndromes showing some
      special features regarding its etiology and clinical manifestations. Less than
      10% of gliomas may be considered as true multicentric tumours either synchronous
      or metachronous in clinical presentation. Metachronous glioblastomas have been
      associated to better prognosis in some studies, with genetic studies having found
      clear differences among the tumors within same patients. Familial glioblastoma
      with metachronous presentation is an exceptional disorder. These tumors show
      special therapeutic implications due to the limitations of radiotherapy once the
      patient has already irradiated. A variety of non-specific mutations have been
      found in these patients but true characterization of this disorder remains
      unclear and will be based on further genetic studies. We present a clinical
      report on a patient harbouring a familial and metachronous glioblastoma. The main
      aspects of this entity are reviewed.

PMID- 16960646
TI  - "Benign" shaken baby syndrome. Case report.
AB  - The authors report an infant with clinical and neuroimaging findings of shaken
      baby syndrome. The pitfalls encountered in the assessment on the cause of the
      bilateral frontal and interhemispheric subdural hematomas in this child are also
      briefly discussed. We have called this condition "benign" shaken baby syndrome
      and emphasize that not always acute subdural hematomas are of non-accidental
      nature.

PMID- 16960647
TI  - [Frontal sinus obliteration using tibial bone graft and platelet-rich plasma for
      the treatment of chronic osteomyelitis].
AB  - OBJECTIVES: The more successfully surgical treatment for the treatment of chronic
      frontal sinusitis complicated with chronic osteomielitis, is the cleaning and
      curettage of the sinus with obliteration of the sinus cavity and nasofrontal
      duct. Several autologous and alloplastics materials are used for this
      obliteration. MATERIAL AND METHODS: We report the case of a patient previously
      operated on because of frontal sinus plasmocytoma who developed frontal sinusitis
      with chronic osteomielitis and cutaneous suppuration. He received surgical
      treatment with frontal sinus curettage and obliteration with tibial bone graft
      and platelet-rich plasma (PRP). Symptoms disappeared and there were no
      complications or recurrence. CONCLUSIONS: Obliteration of the frontal sinus with
      tibial bone graft and PRP after sinus cleaning and curettage can be a good
      alternative in the treatment of chronic frontal sinus osteomielitis.

PMID- 16960648
TI  - Bone density and bone area in Canadian Aboriginal women: the First Nations Bone
      Health Study.
AB  - INTRODUCTION: Canadian Aboriginal women are at increased risk of fracture
      compared with the general population. HYPOTHESIS: There is disproportionately
      reduced bone density in Aboriginal women as compared to white females of similar
      age. METHODS: A random age-stratified (25-39, 40-59 and 60-75) sample of
      Aboriginal women (n=258) and white women (n=181) was recruited. All subjects had
      calcaneus and distal forearm bone density measurements, and urban participants
      (n=397 [90.4%]) also had measurements of the lumbar spine, hip and total body.
      RESULTS: Unadjusted measurements were similar in the two groups apart from the
      distal forearm which showed a significantly lower mean Z-score in the Aboriginal
      women (p=0.03). Aboriginal women were heavier than white women (81.0+/-18.0 kg
      vs. 76.0+/-18.0 kg, p=0.02). Weight was directly associated with BMD at all
      measurement sites (p<0.00001) and potentially confounded the assessment of
      ethnicity on bone mass measurements. Weight-adjusted ANCOVA models demonstrated
      significantly lower bone density in Aboriginal than white women for the
      calcaneus, distal forearm, and total body (all p<0.05), but not at the other
      sites. ANCOVA models (adjusted for age, height and weight) were used to explore
      differences in bone area and bone mineral content (BMC). There was a significant
      effect of ethnicity on bone area with Aboriginal women having larger adjusted
      mean values than white women (lumbar spine p=0.038, total hip p=0.0004, total
      body p=0.020). In contrast, there was no detectable effect of ethnicity on BMC
      (all p>0.2). CONCLUSIONS: We identified significant site-specific differences in
      age-and weight-adjusted bone density for Aboriginal and white women. Larger bone
      area, rather than a reduction in BMC, appeared to be primarily responsible.
      Further work is needed to define how these differences in bone density and
      geometry affect indices of bone strength.

PMID- 16960649
TI  - An agenda for future debate on concepts of health and disease.
AB  - The traditional contrast between naturalist and normativist disease concepts
      fails to capture the most salient features of the health concepts debate. By
      using health concepts as a window on background notions of medical science and
      ethics, I show how Christopher Boorse (an influential naturalist) and Lennart
      Nordenfelt (an influential normativist) actually share deep assumptions about the
      character of medicine. Their disease concepts attempt, in different ways, to
      shore up the same medical model. For both, health concepts function like
      demarcation criteria in the philosophy of science: they mark off the jurisdiction
      of medical science, and protect it from an inappropriate intrusion of
      socioeconomic factors, which threaten the integrity of modern medicine. These
      views are challenged by new developments in healthcare such as managed care and
      total quality review. To frame the health concepts debate in a way that better
      captures the issues integral to these new developments, I advance a new way of
      reading the distinction between weak and strong normativists. Strong normativists
      are skeptical of the demarcation project, think facts and values cannot be
      disentangled, and hold that socioeconomic conditions unavoidably influence how
      pathology is understood. The new health concepts debate should be framed as one
      between weak and strong normativists, and it concerns how we should respond to
      the current developments in health care.

PMID- 16960650
TI  - Introducing a model for communicable diseases surveillance: cell phone
      surveillance (CPS).
AB  - BACKGROUND AND GOAL: Surveillance systems for communicable diseases are primarily
      passive in most countries, including Iran. Laboratory-based surveillance and use
      of cell phone surveillance may be a useful method. MATERIAL AND METHOD: We
      established a new model for gathering data directly from district laboratories to
      regional laboratories and from them to national manager of public health
      laboratories by using cell phone. We assessed the coverage of Mobile and Cell
      phone in the laboratory Technicians, and Directors of Public Health in 27
      universities in Iran by a simple data collection form to evaluate the feasibility
      of this method. And then this method was piloted for the last Cholera outbreak in
      Iran in 2005. RESULT: From data of 27 universities with 184 cities, we gathered
      769 data health directors' mobile, total mobile penetrating rate, SMS users, and
      SMS penetrating rate was 57.9%, 77.1%, and 44.6% between Directors in Medical
      Universities of Iran and 54.5%, 54.9% and 29.9% in Directors of Laboratory. In
      the Cholera epidemic in Iran in summer 2005, CDC of MOH registered near 900 cases
      of cholera from 70000 rectal soap's exam in whole of country. The median
      reporting interval was under one day. CONCLUSION: Although the advent of the cell
      phone will probably change the way in which surveillance is delivered by health
      system, further studies are warranted to evaluate this method for laboratory
      based surveillance of lethal infections.

PMID- 16960651
TI  - Insight and regional brain volumes in schizophrenia.
AB  - We have investigated the relationship between insight impairment and regional
      brain volumes (gray and white matter) in schizophrenia using voxel-based
      morphometry (VBM). Fifty patients with schizophrenia were evaluated using the
      Scale for Unawareness of Mental Disorders. Magnetic resonance images were
      acquired, segmented and spatially normalized using optimized VBM routines. No
      significant inverse correlations were detected between insight impairment and
      gray or white matter volumes in the prefrontal region (where significant findings
      had been predicted a priori), or in any other brain areas. Our results do not
      support previous hypotheses suggesting a relationship between frontal lobe
      atrophy and impaired insight in patients with schizophrenia.

PMID- 16960652
TI  - Cerebral atrophy and white matter disruption in chronic schizophrenia.
AB  - Several magnetic resonance imaging (MRI) studies have shown cerebral atrophy in
      established schizophrenia, although not in all reports. Discrepancies may mostly
      be due to population and postprocessing differences. Recently, disruption of
      cortical white matter integrity has also been reported in chronic patients with
      schizophrenia. In this study we explored tridimensional (3D) cerebral volumes and
      white matter microstructure in schizophrenia with structural and diffusion
      magnetic resonance. Twenty-five patients with established schizophrenia and 25
      1:1 matched normal controls underwent a session of MRI using a Siemens 1.5T
      scanner. 3D brain volume reconstruction was performed with the semi-automatic
      software Amira (TGS, San Diego, CA), whereas the apparent diffusion coefficients
      (ADCs) of cortical white matter water molecules were obtained with in-house
      developed softwares written in MatLab (The Mathworks-Inc., Natick, MA). Compared
      to controls, patients with schizophrenia had significantly smaller gray matter
      intracranium and total brain volumes, increased 4th ventricle volumes, and
      greater temporal and occipital ADCs. Patients treated with typical antipsychotic
      medication (N = 9) had significantly larger right lateral and 4th ventricles
      compared to those on atypical antipsychotic drugs. Intracranial volumes
      significantly inversely correlated with left temporal ADC in patients with
      schizophrenia. Also, age correlated directly with right, left, and 3rd ventricle
      volumes and inversely with gray matter intracranium volumes in individuals with
      schizophrenia. This study confirmed the presence of cortical atrophy in patients
      with schizophrenia, especially in those on typical antipsychotic drugs, and the
      existence of white matter disruption. It also suggested that physiological aging
      effects on brain anatomy may be abnormally pronounced in schizophrenia.

PMID- 16960653
TI  - Decreased quality of life and depression as predictors for shorter survival among
      patients with low-grade gliomas: a follow-up from 1990 to 2003.
AB  - OBJECTIVES: To assess the long-term survival of brain tumor patients, and in
      particular to evaluate the relation of quality of life (QOL) to survival among
      low-grade glioma patients. METHODS: The postoperative survival of 101 brain tumor
      patients was followed from surgery (1990-1992) until the end of the year 2003.
      Depression was evaluated by the Beck Depression Inventory (BDI) and QOL with
      Sintonen's 15D scale before operation and at one year as well as at five years
      after operation. RESULTS: The mean survival times in years (SD) were
      significantly related to tumor malignancy, being the shortest, 1.9 (0.6), for
      patients with high-grade gliomas, while patients with low-grade gliomas or a
      benign brain tumor had mean survival times of 9.1 (1.0) and 11.6 (0.5),
      respectively. At all follow-ups, depressed low-grade glioma patients had a
      significantly shorter survival time, 3.3-5.8 years, compared to non-depressed low
      grade glioma patients, 10.0-11.7 years. A decreased level of QOL in low-grade
      glioma patients was significantly related to the shorter survival. CONCLUSIONS:
      The results suggest that depression and decreased QOL among low-grade glioma
      patients is related to shorter survival at long-term follow-up. Decreased QOL may
      serve as an indicator for poor prognosis in low-grade glioma patients.

PMID- 16960654
TI  - The continuum/spectrum concept of mood disorders: is mixed depression the basic
      link?
AB  - BACKGROUND: Mixed states, i.e., opposite polarity symptoms in the same mood
      episode, question the bipolar/unipolar splitting of mood disorders, and support a
      spectrum view. Study aim was assessing the distribution of intradepressive
      hypomanic symptoms between bipolar-II (BP-II) and major depressive disorder (MDD)
      depressions, and testing a dose-response relationship between number of
      intradepressive hypomanic symptoms and bipolar family history. No bi-modality,
      and a dose-response relationship, would not support a categorical distinction.
      METHODS: Consecutive 389 BP-II and 261 MDD depressed outpatients were interviewed
      by the structured clinical interview for DSM-IV, hypomania interview guide, and
      family history screen, by a mood specialist psychiatrist, in a private practice.
      Intradepressive hypomanic symptoms were systematically assessed. Mixed depression
      was defined as the combination of depression and three or more intradepressive
      hypomanic symptoms, a validated definition. RESULTS: BP-II, versus MDD, had
      significantly more intradepressive hypomanic symptoms. The distribution of
      intradepressive hypomanic symptoms between BP-II and MDD was not bi-modal but
      normal-like, and a dose-response relationship was found between the number of
      intradepressive hypomanic symptoms and bipolar family history. CONCLUSIONS: Study
      findings question the categorical division of BP-II and MDD, and may support the
      spectrum view of mood disorders.

PMID- 16960655
TI  - Epidemiologic and clinical updates on impulse control disorders: a critical
      review.
AB  - The article reviews the current knowledge about the impulse control disorders
      (ICDs) with specific emphasis on epidemiological and pharmacological advances. In
      addition to the traditional ICDs present in the DSM-IV-pathological gambling,
      trichotillomania, kleptomania, pyromania and intermittent explosive disorder-a
      brief description of the new proposed ICDs-compulsive-impulsive (C-I) Internet
      usage disorder, C-I sexual behaviors, C-I skin picking and C-I shopping-is
      provided. Specifically, the article summarizes the phenomenology, epidemiology
      and comorbidity of the ICDs. Particular attention is paid to the relationship
      between ICDs and obsessive-compulsive disorder (OCD). Finally, current
      pharmacological options for treating ICDs are presented and discussed.

PMID- 16960656
TI  - Downregulation of hnRNP C1/C2 by siRNA sensitizes HeLa cells to various stresses.
AB  - The heterogeneous nuclear ribonucleoprotein C1/C2 is one of the most abundant
      proteins in the nucleus, and shown to have roles in cellular differentiation and
      proliferation through post-transcriptional regulations of certain mRNA species.
      We studied its role in stress response using siRNA mediated knockdown approach in
      HeLa cells. Upon transient transfection with plasmid encoding siRNA, the cells
      showed increased sensitivities to various chemical agents, namely H(2)O(2,
      )paraquat, camptothecin, ICRF-193 and halogenated deoxyuridines. These results
      demonstrate that hnRNP C1/C2 is involved in maintenance of cellular homeostasis
      besides cellular differentiation and proliferation.

PMID- 16960657
TI  - Chronic exposure to ketone bodies impairs glucose uptake in adult cardiomyocytes
      in response to insulin but not vanadate: the role of PI3-K.
AB  - There is a strong positive correlation between insulin resistance and cardiac
      diseases. We have already shown that chronic exposure to the ketone body beta
      hydroxybutyrate (OHB) decreases insulin-mediated activation of protein kinase B
      (PKB) and glucose uptake in cardiomyocytes. To gain further insights into the
      mechanism underlying ketone body-induced insulin resistance, we examined whether
      OHB alters activation of the insulin-signaling cascade and whether the
      insulinomimetic agent vanadate could bypass insulin resistance and stimulate
      glucose uptake in these cells. Cardiomyocytes were incubated with 5 mM OHB, 50
      microM vanadate or both for 16 h before the measurement of glucose uptake or the
      activation of insulin-signaling molecules. While chronic exposure to OHB did not
      alter insulin- or vanadate-mediated activation of the insulin receptor, it
      suppressed insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation in
      response to both agonists. Furthermore, this treatment decreased by 54 and 36%
      the phosphorylation of the p85 regulatory subunit of phosphatidylinositol 3
      kinase (PI3-K) and PKB in response to insulin, whereas it did not alter vanadate
      mediated activation of these enzymes. Although insulin did not significantly
      stimulate p38MAPK phosphorylation, vanadate increased it by 3.8-fold.
      Furthermore, chronic exposure to OHB potentiated vanadate's action, resulting in
      a 250% increase in enzyme activation compared to control cells. Though OHB
      induced a 2.1-fold increase of basal ERK1/2 phosphorylation, inhibition of this
      enzyme with the MEK inhibitor PD98059 demonstrated that ERK1/2 did not
      participate in OHB-induced insulin resistance. In conclusion, ketone bodies
      promote insulin resistance probably through decreased activation of the PI3-K/PKB
      signaling cascade. Furthermore, vanadate can bypass insulin resistance and
      stimulate glucose uptake in OHB-treated cardiomyocytes.

PMID- 16960660
TI  - Application of in-situ bioassays with macrophytes in aquatic mesocosm studies.
AB  - Aquatic mesocosm studies assess ecotoxicological effects of chemicals by using
      small artificial ponds as models of lentic ecosystems. In this study, methods of
      controlled insertion of macrophytes within an outdoor mesocosm study were
      explored. Although analytically confirmed concentrations of the model herbicide
      terbuthylazine were high enough to expect direct effects on phytoplankton,
      functional parameters and dominant taxa abundance indicated only minor and
      transient effects. In-situ assays with Lemna minor, Myriophyllum spicatum,
      Potamogeton lucens and Chara globularis revealed adverse effects at
      concentrations in accordance with literature data. Complex interactions such as
      nutrient limitation and competition were possible reasons for the observed growth
      promotion at the lower concentration of about 5 microg/l terbuthylazine. The
      approach of macrophyte in-situ bioassays within a mesocosm study proved to be
      applicable. Presumed advantages are simultaneous acquisition of toxicity data for
      several species of aquatic plants under more realistic conditions compared to
      laboratory tests and inclusion of macrophytes as important structural and
      functional components in mesocosms while limiting their domination of the model
      ecosystem.

PMID- 16960659
TI  - Hepatitis B virus replication causes oxidative stress in HepAD38 liver cells.
AB  - We used human hepatoma HepAD38 cells, in which HBV production is under the
      control of a tetracycline-regulated promotor, to investigate changes induced in
      the host cell by HBV replication that could contribute to malignant
      transformation. Parameters of oxidative stress (malondialdehyde, glutathione) and
      cell proliferation were determined at different times after induction (0-96 h).
      In HBV-producing cells, the redox status peaked at 72 h. cDNA micro array
      analysis at 72 h post induction revealed 3 groups of genes that were up-regulated
      by HBV: (i) heat shock proteins, (ii) oxidative and metabolic stress and (iii)
      growth and apoptosis related genes. Continuous HBV production did not accelerate
      karyotypic changes in cells cultured for 4 months (18 passages). IN CONCLUSION:
      HBV replication modulates host gene expression and induces oxidative stress. In
      this HepAD38 model early events (0-4 days) in the host cell after induction of
      HBV replication can be studied under strictly defined conditions.

PMID- 16960658
TI  - Modulation of function of three ABC drug transporters, P-glycoprotein (ABCB1),
      mitoxantrone resistance protein (ABCG2) and multidrug resistance protein 1
      (ABCC1) by tetrahydrocurcumin, a major metabolite of curcumin.
AB  - Many studies have been performed with the aim of developing effective resistance
      modulators to overcome the multidrug resistance (MDR) of human cancers. Potent
      MDR modulators are being investigated in clinical trials. Many current studies
      are focused on dietary herbs due to the fact that these have been used for
      centuries without producing any harmful side effects. In this study, the effect
      of tetrahydrocurcumin (THC) on three ABC drug transporter proteins, P
      glycoprotein (P-gp or ABCB1), mitoxantrone resistance protein (MXR or ABCG2) and
      multidrug resistance protein 1 (MRP1 or ABCC1) was investigated, to assess
      whether an ultimate metabolite form of curcuminoids (THC) is able to modulate MDR
      in cancer cells. Two different types of cell lines were used for P-gp study,
      human cervical carcinoma KB-3-1 (wild type) and KB-V-1 and human breast cancer
      MCF-7 (wild type) and MCF-7 MDR, whereas, pcDNA3.1 and pcDNA3.1-MRP1 transfected
      HEK 293 and MXR overexpressing MCF7AdrVp3000 or MCF7FL1000 and its parental MCF-7
      were used for MRP1 and MXR study, respectively. We report here for the first time
      that THC is able to inhibit the function of P-gp, MXR and MRP1. The results of
      flow cytometry assay indicated that THC is able to inhibit the function of P-gp
      and thereby significantly increase the accumulation of rhodamine and calcein AM
      in KB-V-1 cells. The result was confirmed by the effect of THC on [(3)H]
      vinblastine accumulation and efflux in MCF-7 and MCF-7MDR. THC significantly
      increased the accumulation and inhibited the efflux of [(3)H]-vinblastine in MCF
      7 MDR in a concentration-dependent manner. This effect was not found in wild type
      MCF-7 cell line. The interaction of THC with the P-gp molecule was clearly
      indicated by ATPase assay and photoaffinity labeling of P-gp with transport
      substrate. THC stimulated P-gp ATPase activity and inhibited the incorporation of
      [(125)I]-iodoarylazidoprazosin (IAAP) into P-gp in a concentration-dependent
      manner. The binding of [(125)I]-IAAP to MXR was also inhibited by THC suggesting
      that THC interacted with drug binding site of the transporter. THC dose
      dependently inhibited the efflux of mitoxantrone and pheophorbide A from MXR
      expressing cells (MCF7AdrVp3000 and MCF7FL1000). Similarly with MRP1, the efflux
      of a fluorescent substrate calcein AM was inhibited effectively by THC thereby
      the accumulation of calcein was increased in MRP1-HEK 293 and not its parental
      pcDNA3.1-HEK 293 cells. The MDR reversing properties of THC on P-gp, MRP1, and
      MXR were determined by MTT assay. THC significantly increased the sensitivity of
      vinblastine, mitoxantrone and etoposide in drug resistance KB-V-1, MCF7AdrVp3000
      and MRP1-HEK 293 cells, respectively. This effect was not found in respective
      drug sensitive parental cell lines. Taken together, this study clearly showed
      that THC inhibits the efflux function of P-gp, MXR and MRP1 and it is able to
      extend the MDR reversing activity of curcuminoids in vivo.

PMID- 16960661
TI  - Assessment of three year experience of a strategy for patient selection and
      timing of operation in the management of acute thoracic and lumbar spine
      fractures: a prospective study.
AB  - BACKGROUND: The purpose of this article is to report experience gained over three
      years of the use of a protocol for patient selection and timing of operation for
      acute thoracic and lumbar fractures. METHOD: At admission, all patients underwent
      neurological and imaging exams. All patients with a spinal cord lesion scored as
      ASIA A at any level inferior to T10 and as ASIA B, C or D at any level, were
      categorized as emergency and operated on within eight hours from trauma. ASIA A
      cases in the T1-T10 tract and ASIA E cases at any level were treated in the
      ordinary operative work schedule. FINDINGS: Ninety-four patients with surgically
      treated lumbar or thoracic fractures took part in this study. On the imaging
      studies, 12 patients were classified as A, 50 as B and 32 as C following the AO
      classification. At the neurological exam, 39 patients were scored as ASIA A, nine
      as B, six as C, two as D and 38 as E. At follow-up, of the 39 patients scored as
      ASIA A, 13 (33%) improved at least one grade and of the 17 scored as ASIA B, C or
      D, 11 (64.7%) improved. None of the 38 patients scored as ASIA E deteriorated.
      CONCLUSIONS: The findings show that the strategy in the protocol was safe and
      followed by satisfactory rates of neurological outcome. Larger prospective
      studies, preferably randomized, are needed to establish definitively its place in
      the management of patients with spinal injury.

PMID- 16960662
TI  - Open transthoracic or transhiatal esophagectomy versus minimally invasive
      esophagectomy in terms of morbidity, mortality and survival.
AB  - BACKGROUND: Surgical treatment of esophageal cancer is associated with a high
      rate of morbidity and mortality even in specialized centers. Minimally invasive
      surgery has been proposed to decrease these complications. METHODS: The authors
      present their results regarding postoperative complications and the survival rate
      at 3 years, comparing the classic open procedures (transthoracic or transhiatal
      esophagectomy) with minimally invasive surgery. Surgical procedures were
      performed according to procedures published elsewhere. RESULTS: The study
      enrolled 166 patients who underwent surgery between 1990 and 2003. Open
      transthoracic surgery was performed for 60 patients. In this group of patients,
      postoperative mortality was observed in 11% of the cases. Major, minor, and late
      complications were observed in 61.6% of the patients, and the 3-year survival
      rate was 30% for this group. Open transhiatal surgery was performed for 59
      patients. The morbidity, mortality, and 3-year rate were almost the same as for
      the transthoracic surgery group. For the 47 patients submitted to minimally
      invasive procedures (thoracoscopic and laparoscopic), the complications and
      mortality rates were significantly reduced (38.2% and 6.4%, respectively). For
      the patients submitted to minimally invasive surgery, the 3-year survival rate
      was 45.4%. It is important to clarify that the patients submitted to minimally
      invasive surgery manifested early stages of the diseases, and that this the
      reason why the morbimortality and survival rates were better. CONCLUSIONS: The
      transthoracic and transhiatal open approaches have similar early and late
      results. Minimally invasive surgery is an option for patients with esophageal
      carcinoma, with reported results similar to those for open surgery. This approach
      is indicated mainly for selected patients with early stages of the disease.

PMID- 16960663
TI  - An antireflux stent versus conventional stents for palliation of distal
      esophageal or cardia cancer: a randomized clinical study.
AB  - BACKGROUND: Self-expandable metal stents placed across the esophagogastric
      junction for palliative treatment of malignant strictures may lead to
      gastroesophageal reflux and pulmonary aspiration. This study compared the effects
      of a Dua antireflux stent with those of a conventional stent. METHODS: Patients
      with incurable cancer of the distal esophagus or gastric cardia were randomly
      assigned to receive an antireflux stent (n = 19) or a standard stent (n = 22) at
      nine Swedish hospitals during the period September 1, 2003 to July 31, 2005.
      Complications were recorded at clinical follow-up visits. Survival rates were
      assessed through linkage to the Population Register. Dysphagia, reflux symptoms,
      esophageal pain, dyspnea, and global quality of life were assessed as changes in
      mean scores between baseline and 1 month after stent insertion through validated
      questionnaires. RESULTS: No technical problems occurred during stent placement in
      the 41 enrolled patients. Fewer patients with complications were observed in the
      antireflux stent group (n = 3) than in the standard group (n = 8), but no
      statistically significant difference was shown (p = 0.14). The survival rates
      were similar in the two groups (p = 0.99; hazard ratio, 1.0; 95% confidence
      interval, 0.5-2.0). The groups did not differ significantly in terms of studied
      esophageal or respiratory symptoms or quality of life. Clinically relevant
      improvement in dysphagia occurred in both groups. Dyspnea decreased after
      antireflux stent insertion (mean score change, -11), and increased after
      insertion of standard stent (mean score change, +21). CONCLUSIONS: Antireflux
      stents may be used without increased risk of complications, mortality, esophageal
      symptoms, or reduced global quality of life. These results should encourage large
      scale randomized trials that can establish potentially beneficial effects of
      antireflux stents.

PMID- 16960664
TI  - Long-term evaluation of patient satisfaction and reflux symptoms after
      laparoscopic fundoplication with Collis gastroplasty.
AB  - BACKGROUND: Esophageal shortening is a complication of advanced gastroesophageal
      reflux disease (GERD). For patients with short esophagus, Collis gastroplasty
      combined with fundoplication provides excellent symptomatic relief from GERD
      disease. The literature lacks studies comparing satisfaction and reflux symptoms
      between patients who underwent Nissen fundoplication with Collis gastroplasty and
      those who had primary fundoplication alone. This study aimed to assess long-term
      satisfaction and GERD-related quality of life after laparoscopic Collis-Nissen
      fundoplication, and to compare them with those for Nissen fundoplication alone.
      METHODS: A nested case-control study was conducted. In this study, 14 cases of
      laparoscopic Collis-Nissen fundoplications were matched for age, gender, and
      length of the follow-up period to a cohort of 120 control subjects who underwent
      laparoscopic Nissen fundoplication. All the patients were mailed a follow-up
      survey which included a Short Form-12 (SF-12) health status (quality-of-life)
      questionnaire (a validated quality-of-life instrument), a Quality of Life in
      Reflux and Dyspepsia (QOLRAD) questionnaire (a GERD-specific quality-of-life
      instrument), and queries regarding long-term satisfaction and medication use.
      RESULTS: Both groups showed a significant postoperative increase in QOLRAD mean
      scores (p = 0.01). However, the difference in the delta (postoperative
      preoperative) score between the two groups was not significant (Fig. 1). There
      were no differences in mental (MCS) or physical (PCS) SF-12 scores between the
      two groups. The rate of satisfaction with the surgery was similar in the Nissen
      Collis fundoplication (87.5%) and Nissen fundoplication (87%) groups.
      CONCLUSIONS: Collis gastroplasty combined with Nissen fundoplication is an
      effective procedure for patients with a shortened esophagus diagnosed
      intraoperatively during antireflux surgery. Patient satisfaction, postoperative
      quality of life, and QOLRAD score improvement after this procedure are comparable
      with those observed in patients treated with Nissen fundoplication alone.

PMID- 16960665
TI  - The rise and fall of antireflux surgery in the United States.
AB  - BACKGROUND: National rates of laparoscopic antireflux surgery grew steadily in
      the 1990s. Since then, a highly visible randomized trial has questioned the long
      term effectiveness of antireflux surgery, several new endoscopic therapies have
      been developed, and proton pump inhibitors have become available over the
      counter. Whether these recent developments have had an impact on the use of
      antireflux surgery remains unknown. METHODS: Using data from the Nationwide
      Inpatient Sample, this study identified all patients older than 18 years who
      underwent antireflux surgery between 1994 and 2003. Sampling weights were used to
      estimate the total number of procedures performed in the United States each year.
      Population-based rates were determined using denominators from U.S. census data.
      RESULTS: Confirming the results of earlier studies, this study found that the
      annual number of antireflux procedures grew rapidly during the 1990s, peaking at
      31,695 (15.7 cases per 100,000 adults) in 1999. After 1999, surgical rates
      declined steadily, falling approximately 30% by 2003 to 23,998 (11 cases per
      100,000; p < 0.0001). Use of antireflux procedures fell more precipitously among
      younger patients (39% for 30- to 49-year-olds vs 12.5% for those older than 60
      years; p < 0.0001) and at teaching hospitals (36% vs 23% at nonteaching
      hospitals; p < 0.0001). The proportion of cases managed laparoscopically remained
      stable after 1999. CONCLUSIONS: The use of antireflux surgery in the United
      States has declined substantially. Although other factors may be involved, this
      trend may reflect new questions about the long-term effectiveness of surgery and
      suggests the need for prospective randomized clinical trials assessing current
      therapies.

PMID- 16960666
TI  - Midterm follow-up evaluation after a novel approach to anterior fundoplication
      for achalasia.
AB  - BACKGROUND: This study aimed to compare the outcomes for Heller myotomy alone and
      combined with different partial fundoplications. METHODS: The authors
      retrospectively reviewed their experience with 69 laparoscopic myotomies and 14
      Heller myotomies, 80% of which were performed with partial fundoplication
      including 20 Toupet, 18 Dor, and 17 modified Dor procedures, in which the
      fundoplication is sutured to both sides of the crura and not the myotomy.
      RESULTS: The mean age of the study patients was 69 years (range, 15-80 years).
      Four mucosal perforations were repaired intraoperatively. There was one small
      bowel fistula in an area of open hernia repair distant from the myotomy. One
      patient with severe chronic obstructive pulmonary disease died of pneumonia.
      Phone follow-up evaluation was achieved in 68% of the cases at a mean of 37
      months (range, 2-97 months). The results for no dysphagia and for heartburn
      requiring proton pump inhibitors, respectively, were as follows: Heller myotomy
      (85.7%, 28.5%), Toupet (66.6%, 33.3%), Dor (83.3%, 20%), and modified Dor (84.6%,
      15.3%). Two patients with reflux strictures required annual dilation (Toupet,
      Dor). Two patients required revisions: one redo Heller myotomy (Dor) and one
      esophageal replacement (Toupet). CONCLUSION: Heller myotomy provides excellent
      dysphagia relief with or without fundoplication. Heartburn is a significant
      problem for a minority of patients. In the authors' hands, Toupet had the worst
      results and modified Dor was most protective for heartburn.

PMID- 16960667
TI  - Challenges to the development of complex virtual reality surgical simulations.
AB  - Virtual reality simulation in surgical training has become more widely used and
      intensely investigated in an effort to develop safer, more efficient, measurable
      training processes. The development of virtual reality simulation of surgical
      procedures has begun, but well-described technical obstacles must be overcome to
      permit varied training in a clinically realistic computer-generated environment.
      These challenges include development of realistic surgical interfaces and
      physical objects within the computer-generated environment, modeling of realistic
      interactions between objects, rendering of the surgical field, and development of
      signal processing for complex events associated with surgery. Of these, the
      realistic modeling of tissue objects that are fully responsive to surgical
      manipulations is the most challenging. Threats to early success include
      relatively limited resources for development and procurement, as well as smaller
      potential for return on investment than in other simulation industries that face
      similar problems. Despite these difficulties, steady progress continues to be
      made in these areas. If executed properly, virtual reality offers inherent
      advantages over other training systems in creating a realistic surgical
      environment and facilitating measurement of surgeon performance. Once developed,
      complex new virtual reality training devices must be validated for their
      usefulness in formative training and assessment of skill to be established.

PMID- 16960668
TI  - Laparoscopy for every acute appendicitis?

PMID- 16960669
TI  - Handheld gamma probe used to detect accessory spleens during initial laparoscopic
      splenectomies.
AB  - BACKGROUND: Preoperative determination of the accessory spleen still is a major
      factor in the failure of both laparoscopic and conventional techniques. This
      study aimed to evaluate the practicability and efficacy of a handheld gamma probe
      in identifying accessory spleens at the initial intervention. METHODS: This study
      evaluated 17 patients undergoing laparoscopic splenectomy attributable to benign
      hematologic disorders. All the patients had preoperative ultrasonography,
      computed tomography (CT) scan, and nuclear scintigraphic examination of the
      abdominal cavity to assess the size of the spleen, and to determine the existence
      of the accessory spleen or spleens. For all the patients, a handheld gamma probe
      count was used intraoperatively as an adjuvant method to define the presence and
      location of the accessory splenic tissue. Control nuclear scintigraphic
      examinations of all the patients were performed 1 month after the surgical
      procedure. RESULTS: In two cases, intraoperatively accessory splenic tissue was
      detected by gamma probe, confirming the preoperative CT findings for the
      patients. One of these patients had three accessory spleens, although
      preoperative CT scan showed only two of them. However, by the help of the gamma
      probe, a third spleen located retroperitoneally was defined. For two patients,
      laparoscopic exploration and handheld gamma probe count did not identify any
      accessory splenic tissue, although preoperative CT scan indicated accessory
      spleens. For detecting accessory splenic tissue, the sensitivities of the studied
      techniques were 0% for ultrasonography, 75% for CT scan, 0% for preoperative
      nuclear scintigraphy, 75% for laparoscopic exploration, and 100% for
      perioperative gamma probe examination. CONCLUSION: Preoperative imaging methods
      for accessory spleen determination still have limited benefits because of their
      limited sensitivity. Thus, the handheld gamma probe technique may be an adjuvant
      method for laparoscopic exploration ensuring that no accessory splenic tissue is
      missed during the initial surgical treatment of benign hematologic disorders.

PMID- 16960670
TI  - Does establishing a bariatric surgery fellowship training program influence
      operative outcomes?
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGB) has a long learning curve that may be
      reflected in operative outcomes. This study sought to assess whether training a
      fellow has an impact on the operative outcomes of the training program. METHODS:
      Prospectively collected data on 150 consecutive patients were compared before
      (group 1) and after (group 2) establishment of a fellowship-training program.
      RESULTS: A greater number of patients underwent laparoscopic RYGB (LRYGB) in
      group 2 than in group 1 (63% vs 46%; p = 0.01). The group 2 patients were similar
      to the group 1 patients in terms of age, gender, length of stay, and complication
      rate. However, they had a higher body mass index (BMI) (median 50 kg/m2; range,
      39-64 kg/m2 vs median, 46 kg/m2; range, 38-56 kg/m2; p = 0.01) and a higher
      incidence of prior abdominal procedures (21% vs 7%; p = 0.006). In addition,
      operative time was significantly shorter for the patients who underwent open RYGB
      (ORYGB) (median, 150 min; range, 65-280 min vs median, 110 min; range, 50-210
      min; p < 0.001) and LRYGB (median, 202 min; range, 105-450 min vs median, 134
      min; range, 50-191 min; p < 0.001) in group 2 than for the patients in group 1.
      The patients who underwent ORYGB in groups 1 and 2 had similar characteristics
      and outcomes. Increasing experience with both ORYGB and LRYGB correlated with a
      decrease in operative times for group 2 (p < 0.001), but not for group 1.
      CONCLUSION: Establishment of a fellowship program shortens the operative times
      for both open and laparoscopic RYGB and expands the scope of bariatric practice
      by compounding the experience of the operating team without increasing
      complications.

PMID- 16960671
TI  - Minimally invasive enucleation of esophageal leiomyoma.
AB  - BACKGROUND: Leiomyoma accounts for 70% of all benign tumors of the esophagus.
      Open enucleation via thoracotomy has long been the standard procedure, but
      thoracoscopic and laparoscopic approaches have recently emerged as interesting
      alternatives. To date, only case reports or very small series of such techniques
      have been reported. The authors report their experience over the past decade.
      METHODS: Between January 1999 and August 2005, 11 patients (6 men and 5 women;
      median age, 44 years) underwent surgery after presenting with dysphagia, chest
      pain, or heartburn. The surgical approaches included right video-assisted
      thoracoscopy (n = 7) for tumors of the middle lower third of the esophagus and
      laparoscopy (n = 4) for tumors within 4 to 5 cm of the lower esophageal sphincter
      or located at the gastroesophageal junction (GEJ). Intraoperative endoscopy with
      air insufflation during enucleation was used to confirm mucosal integrity and
      safeguard against esophageal perforation. Reapproximation of the muscle layers
      was performed after tumor enucleation to prevent the development of a
      pseudodiverticulum. A Nissen or Toupet fundoplication was added for patients
      undergoing laparoscopic enucleation of the leiomyoma. RESULTS: The median
      operative time was 150 min. All tumors were benign leiomyomas (median size, 4.5
      cm). One leiomyoma located at the gastroesophageal junction required
      intraoperative mucosal repair with three stitches for an esophageal perforation
      (preoperative biopsies had been taken). There were no major morbidities,
      including deaths or postoperative leaks. The median postoperative hospital stay
      was 6 days. All the patients were free of dysphagia during a median followup
      period of 27 months. One patient had a small (< 2 cm) asymptomatic
      pseudodiverticulum at the 6-month follow-up endoscopy. CONCLUSIONS: Video
      assisted enucleation of esophageal leiomyoma can be performed effectively and
      safely with no mortality and low morbidity. Thoracoscopic and laparoscopic
      techniques for the removal of esophageal leiomyomas may be recommended as the
      treatment of choice in centers experienced with minimally invasive surgery.

PMID- 16960672
TI  - Direct visual insertion of primary trocar and avoidance of fascial closure with
      laparoscopic Roux-en-Y gastric bypass.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (RYGBP) has been used
      increasingly more often in the past 10 years. The authors summarize their
      experience and safety/complications data based on 849 laparoscopic RYGBP
      procedures. They also evaluate the use of the Endopath trocar in terms of trocar
      site hernias, bowel obstruction, and elimination of time-consuming fascial
      closure. METHODS: From July 2000 to December 2003, 849 laparoscopic RYGBP
      procedures were performed using a bladeless, 12-mm, visual entry trocar. The
      patients' average body mass index (BMI) was 53.2 kg/m2. The trocar ports (n =
      3,744) were not closed. Perioperative and postoperative assessments were
      performed. RESULTS: In this study, 74% of the patients were retained for follow
      up evaluation (mean, 10 months). Among these patients, no intraoperative bowel or
      vascular injuries, no mortality, and two trocar-site hernias (0.2%) were found.
      At 1 year, the mean excess weight loss was 73.4%. CONCLUSIONS: The Endopath
      trocar system shows a trend toward reducing trocar-site hernias, decreasing bowel
      obstruction, and eliminating the need for time-consuming fascial closure,
      although further studies are needed to confirm these findings.

PMID- 16960673
TI  - Endoscopic treatment of pancreatic fistulas.
AB  - BACKGROUND: Pancreatic fistulas are managed primarily by conservative treatment.
      Surgery is performed in cases of conservative treatment failure. Endoscopic
      treatment is reported to be both effective and safe as an alternative treatment
      method. METHODS: A total of 26 patients underwent endoscopic treatment after
      failure of conservative treatment between January 2002 and November 2004. The
      mean time between the onset of fistula and the endoscopic retrograde
      cholangiopancreatography (ERCP) procedure was 95 days. The mean fistula output
      volume was 400 ml per day. Four patients had pancreatic ascites. The aim of the
      endoscopic treatment was to bypass the ductal disruption by placing stents or
      drains where the origin of fistulous tract could be identified, and to lower the
      pancreatic duct pressure by performing pancreatic sphincterotomy or by placing
      stents where the site of the leak could not be identified. RESULTS:
      Pancreatography could be performed in all the patients except one. Partial duct
      disruption occurred in 16 patients. All of the fistulas closed after the ductal
      disruption was bypassed. Pancreatic sphincterotomy or endoprothesis placement was
      effective for eight of the remaining nine patients in whom the ductal disruption
      originated from the tail of the pancreas and hence could not be bypassed. The
      overall success rate was 94% for the patients with partial duct disruption. Four
      patients had side branch leaks. All of them closed after placement of an
      endoprothesis. Fistulas closed in only one (20%) of the five patients with
      complete duct disruption. Pancreatic ascites resolved in two of the four patients
      after endoscopic treatment. No serious complications resulted from endoscopic
      treatment other than proximally migrated stents in two patients. CONCLUSIONS:
      Endoscopic treatment is an effective and safe method for patients with pancreatic
      fistulas unresponsive to conservative treatment. The success rate is very high,
      especially for patients with partial and side branch duct disruption.

PMID- 16960674
TI  - Retroperitoneoscopic lumbar sympathectomy for the treatment of plantar
      hyperhidrosis: technique and preliminary findings.
AB  - BACKGROUND: Patients with plantar hyperhidrosis suffer physically and mentally
      from a disease that often cannot be treated sufficiently using conservative
      measures. This article reports the authors' experience with endoscopic lumbar
      sympathectomies for patients with plantar hyperhidrosis. METHODS: Bilateral
      lumbar sympathectomy was performed for eight patients (3 women and 5 men). A
      retroperitoneoscopic surgical technique was used, during which the lower lumbar
      sympathetic trunk was resected after radiologic localization of the lumbar spine,
      with care taken to protect the cranial lumbar ganglia. RESULTS: All 16
      sympathectomies were conducted retroperitoneoscopically, with no intra- or
      postoperative complications. In all cases, pedal sweat secretion was completely
      suspended postoperatively. After a 3- to 8-month follow-up period, the anhidrosis
      persisted in all cases (100%). None of the patients experienced sexual
      dysfunction. Five patients (62%) reportedly experienced minor compensatory
      sweating of the torso, and four patients (50%) had postsympathectomy neuralgia.
      Seven of eight patients were very happy with the postoperative results and would
      agree to a repeat of the intervention any time. CONCLUSIONS: Retroperitoneoscopic
      resection of the lower lumbar sympathetic trunk is a safe and effective procedure
      for obtaining suspension of excessive sweat secretion in patients with plantar
      hyperhidrosis that cannot be treated with conservative methods.

PMID- 16960675
TI  - Video-assisted central compartment lymphadenectomy in a patient with a positive
      RET oncogene: initial experience.
AB  - BACKGROUND: Prophylactic surgery for patients carrying a positive RET proto
      oncogene proved to be highly effective in curing those likely to experience the
      development of a medullary carcinoma. Video-assisted procedures have been proved
      feasible for central compartment dissection. METHODS: A total of 15 patients (7
      men and 8 women) with a positive RET proto-oncogene underwent total thyroidectomy
      and central compartment lymphadenectomy via a video-assisted approach. The mean
      age of the patients was 32.5 years. The echographically estimated mean volume was
      10.3 ml, and the mean diameter of the main nodule was 8.8 mm. Preoperative
      ultrasound showed an absence of lateral neck lymph node involvement in all cases.
      No drain was used. Direct laryngoscopy was performed in all cases 1 month after
      surgery. RESULTS: The mean operative time was 67.3 min. A transient
      hypoparathyroidism occurred in one patient, and a permanent hypoparathyroidism
      occurred in another patient. No laryngeal nerve palsy was present. All the
      patients were discharged on postoperative day 1. Histology showed a medullary
      carcinoma in 10 patients and diffuse C-cell hyperplasia in 5 patients. The mean
      number of lymph nodes removed was 5.1. None of these nodes proved to be
      metastatic. Calcitonin levels were undetectable in all six patients who had a
      follow-up period longer than 1 year. CONCLUSION: Video-assisted central
      compartment lymphadenectomy was proved to be effective and safe. The procedure
      demonstrated a complication rate comparable with that for the conventional
      procedure, a better cosmetic outcome, and less postoperative pain. Although the
      video-assisted access proved to be a valid option for the treatment of patients
      carrying a positive RET proto-oncogene, a greater number of cases with a longer
      follow-up period is necessary to estimate the impact of the video-assisted
      approach on central neck lymphadenectomy.

PMID- 16960676
TI  - Multidimensional learning curve in laparoscopy-assisted gastrectomy for early
      gastric cancer.
AB  - BACKGROUND: Laparoscopy-assisted gastrectomy (LAG) is a complex and time
      consuming procedure, which is increasingly used for early gastric cancer (EGC).
      We provide a multidimensional analysis of the learning curve in LAG. METHODS:
      Cumulative sum method was used to analyze outcomes of 109 patients undergoing LAG
      for EGC by one surgeon over a two year period; the influence of patient selection
      was evaluated. Target failure rate was set at 10%, with failure defined as open
      conversion, mortality, major morbidity, residual tumor, or inappropriate
      lymphadenectomy. RESULTS: There were 19 failures--fourteen performance and five
      oncologic. The learning curve, which displayed a slight rising trend and three
      phases was achieved after 40 cases with selected patients; it was broken,
      however, by the introduction of advanced procedures and unselected patients.
      CONCLUSIONS: Advanced procedures and broad indications in LAG should be delayed
      until a learning curve is completed under the target failure rate.

PMID- 16960677
TI  - Technique for instant stapling of the sigmoid mesentery and mesorectum in
      laparoscopic colorectal surgery.
AB  - BACKGROUND: Dissection of the mesentery of the distal sigmoid or rectum before
      transection with a linear stapler in laparoscopic colorectal surgery is time
      consuming, can cause irritating bleeding, and can harm the vascularization of the
      distal part of the bowel anastomosis. METHODS: A new linear stapling technique in
      laparoscopic colorectal surgery is presented. This technique is used to perform
      transection of the distal sigmoid or proximal rectum with a linear stapler by
      instant stapling of both the mesentery/mesorectal fat and the intestine instead
      of standard preliminary dissection. This technique was performed in a pilot study
      of 27 laparoscopic colorectal operations for benign or malignant disease.
      RESULTS: In none of the 27 patients was leakage of the anastomosis observed.
      CONCLUSIONS: This new technique is safe and effective. It saves time, avoids
      troublesome dissection of the mesentery/mesorectum, which can cause bleeding or
      damage to the bowel, and preserves vascularization of the distal part of the
      anastomosis.

PMID- 16960678
TI  - Minimal access approach to the management of large ovarian cysts.
AB  - Laparoscopy has become an accepted method of management for ovarian cysts. Large
      ovarian cysts, however, have traditionally been, and continue to be treated by
      laparotomy. This is mainly due to technical difficulties and the possibility of
      malignancy. We describe four patients in whom laparoscopy was used to remove
      large ovarian cysts. Laparoscopic guided aspiration was performed, followed by
      extra-abdominal excision of the cyst. This approach has the advantages of
      minimising the risk of spillage of cyst fluid, a smaller incision compared to
      laparotomy, as well as faster recovery. We advocate this method for large
      unilocular benign cysts.

PMID- 16960679
TI  - Low conjunction of the cystic duct with the common bile duct: does it correlate
      with the formation of common bile duct stones?
AB  - BACKGROUND: This study aimed to evaluate the accuracy of magnetic resonance
      cholangiography (MRC) in detecting variants of low cystic duct conjunction, which
      can be a source of confusion during surgery when unrecognized. METHODS: All cases
      with both MRC and endoscopic retrograde cholangiography (ERC) indicating
      suspected common bile duct stones between January 1999 and January 2004 were
      retrospectively reviewed by investigators blinded to the final diagnosis.
      Assessment with ERC was regarded as the gold standard. The aim was to find a low
      conjunction of the cystic duct with the bile duct. The sensitivity and
      specificity of MRC were calculated in comparison with those for ERC. The cystic
      junction radial orientation was defined as lateral (insertion diagonally from the
      right), medial (insertion into the left side of the common hepatic duct), or
      posteroanterior (overlap of the junction with the bile duct in the
      posteroanterior view). A spiral cystic duct and a long parallel course were
      evaluated separately. RESULTS: Low insertion of the cystic duct was found on ERC
      in 66 of 622 patients (11%; 28 men and 38 women; mean age, 64.5 years). The
      sensitivity and specificity of MRC for detecting low cystic entrance were 100%
      (90.4% on an intention-to-diagnose basis and 100%, respectively). In 11 patients
      (16.6%), the radial orientation of the cysticohepatic junction could not be
      defined with MRC. The rate of correct MRC delineation was 95% for lateral (n =
      21), 77% for medial (n = 26), and 74% for posteroanterior (n = 19) insertion of
      the cystic duct. CONCLUSION: The findings showed that MRC has good correlation
      with ERC with regard to the location and anatomic details of cystic duct
      insertion. Although this does not generate a separate indication for MRC before
      laparoscopic cholecystectomy, the anatomic information can be of additional use
      when MRC is clinically indicated in this setting.

PMID- 16960680
TI  - Palanivelu hydatid system for safe and efficacious laparoscopic management of
      hepatic hydatid disease.
AB  - BACKGROUND: Hydatid disease, being endemic in several areas of the world, is of
      interest even to surgeons in non-endemic areas because they may encounter the
      disease due to ease and rapidity of travel as well as immigration. We describe a
      new device for laparoscopic management of hepatic hydatid disease. METHODS: The
      special trocar-cannula system--the Palanivelu hydatid system (PHS)--and the
      technique of operation are described. A total of 75 patients were operated on
      using this technique. RESULTS: In 83.3% of patients, only evacuation of the
      hydatid cyst by the PHS was done. In 13.7%, this was followed by left lobectomy
      because the cysts were large, occupying almost the entire left lobe of the liver.
      The remnant cavity was dealt with by omentoplasty. The average follow-up period
      was 5.9 years, during which there were no recurrences. CONCLUSIONS: PHS is
      successful in preventing spillage, evacuating the contents of hydatid cysts,
      performing transcystic fenestration, and for dealing with cyst-biliary
      communications.

PMID- 16960681
TI  - Does experience preclude leaks in laparoscopic gastric bypass?
AB  - BACKGROUND: Improved outcomes of laparoscopic Roux-en-Y gastric bypass (LRYGB)
      have been demonstrated once pratice has moved beyond the learning curve. However,
      there is no evidence that experience has a favorable impact on the incidence of
      leaks. This study evaluated the incidence of staple-line leaks as experience
      accrued in a university-based bariatric surgery program. METHODS: Prospectively
      collected data on our first 200 patients undergoing LRYGB since July 1998 were
      analyzed. Linear staplers were used to divide the stomach and to create a side-to
      side jejunojejunostomy. A side-to-side cardiojejunostomy was created using a 21
      mm circular stapler. Patient characteristics, operative data, and outcomes were
      evaluated chronologically with comparison of outcomes between quartiles. RESULTS:
      Staple-line leaks developed in 9 (4.5%) of the first 200 patients undergoing
      LRYGB. Among the 200 patients were 190 women (95%). The median age of the
      patients was 48 years (ranges, 24-62 years), and their body mass index was 43
      kg/m(2) (ranges, 32-59 kg/m(2)). As surgeons' experience increased over time,
      there was a significant increase in the weight of patients and the percentage of
      patients with previous abdominal operations. There also was a significant
      decrease in conversion rates and operative times. Leaks occurred in six patients
      at the cardiojejunostomy (3%), in two patients jejunojejunostomy (1%), and in one
      patient at the excluded stomach (0.5%). Of the 50 leaks that occurred in each
      quartile, there were in the 3 in the 1st quartile, 1 in the 2nd quartile, 2 in
      the 3rd quartile, 3 in the 4th quartile. The differences were not significant.
      There was no correlation between the number of LRYGBs, and the occurrence of a
      leak (p = 0.59 confidence interval -0.13-0.22). CONCLUSIONS: The incidence of
      staple-line leaks appears to be independent of the number of LRYGBs performed.
      These data suggest that surgeons' experience may not eliminate anastomotic
      complications experienced by patients undergoing LRYGB.

PMID- 16960682
TI  - Prognosis of breast cancer after supraclavicular lymph node metastasis: not a
      distant metastasis.
AB  - BACKGROUND: We performed this study to analyze the survival of breast cancer
      patients with isolated supraclavicular lymph node metastasis (SLNM) and assess
      whether SLNM is distant metastasis or not. METHODS: Sixty-three patients who
      developed an isolated SLNM among 3170 primary breast cancer patients between 1990
      and 1999 were enrolled. The survival after SLNM was compared with that of 151
      patients who developed local recurrences and 599 who had distant metastasis and
      was analyzed according to different levels and numbers of positive axillary
      nodes. RESULTS: Thirty-five of the 63 patients died during a median follow-up of
      58.3 months. The 5-year overall survival (OS) rates after SLNM, local relapse,
      and distant metastasis were 33.6%, 34.9%, and 9.1%, respectively. The 5-year OS
      for patients with involved nodes confined to axillary level I was 74.4%, which
      was significantly better than that for involved nodes in level II or III or SLNM
      (49.2%, 52.8%, and 33.6%, respectively; P < .0001). For one to three positive
      axillary nodes, the 5-year OS was 83.2%, which was significantly better than that
      for four to nine positive nodes, more than nine positive nodes, and SLNM (62.6%,
      42.3%, and 33.6%, respectively). There was no significant difference between SLNM
      and more than nine positive nodes. Surgical removal of the supraclavicular nodes
      was a significantly better prognostic factor for OS after SLNM (P = .0327).
      CONCLUSIONS: The 5-year OS after supraclavicular nodal metastosis, local relapse,
      and distant metastasis were 33.6%, 34.9%, and 9.1%, respectively. Good neck
      control either by surgery or chemotherapy achieved better survival.

PMID- 16960683
TI  - A presentation system for just-in-time learning in radiology.
AB  - There is growing interest in bringing medical educational materials to the point
      of care. We sought to develop a system for just-in-time learning in radiology. A
      database of 34 learning modules was derived from previously published journal
      articles. Learning objectives were specified for each module, and multiple-choice
      test items were created. A web-based system-called TEMPO-was developed to allow
      radiologists to select and view the learning modules. Web services were used to
      exchange clinical context information between TEMPO and the simulated radiology
      work station. Preliminary evaluation was conducted using the System Usability
      Scale (SUS) questionnaire. TEMPO identified learning modules that were relevant
      to the age, sex, imaging modality, and body part or organ system of the patient
      being viewed by the radiologist on the simulated clinical work station. Users
      expressed a high degree of satisfaction with the system's design and user
      interface. TEMPO enables just-in-time learning in radiology, and can be extended
      to create a fully functional learning management system for point-of-care
      learning in radiology.

PMID- 16960684
TI  - Activation of PPAR-delta in isolated rat skeletal muscle switches fuel preference
      from glucose to fatty acids.
AB  - AIMS/HYPOTHESIS: GW501516, an agonist of peroxisome proliferator-activated
      receptor-delta (PPAR-delta), increases lipid combustion and exerts antidiabetic
      action in animals, effects which are attributed mainly to direct effects on
      skeletal muscle. We explored such actions further in isolated rat skeletal
      muscle. MATERIALS AND METHODS: Specimens of rat skeletal muscle were pretreated
      with GW501516 (0.01-30 mumol/l) for 0.5, 4 or 24 h and rates of fuel metabolism
      were then measured. In addition, effects on mitochondrial function were
      determined in isolated rat liver mitochondria. RESULTS: At concentrations between
      0.01 and 1 mumol/l, GW501516 dose-dependently increased fatty acid oxidation but
      reduced glucose utilisation in isolated muscle. Thus after 24 h of preincubation
      with 1 mumol/l GW501516, palmitate oxidation increased by +46+/-10%, and the
      following decreased as specified: glucose oxidation -46+/-8%, glycogen synthesis 
      42+/-6%, lactate release -20+/-2%, glucose transport -15+/-6% (all p<0.05).
      Reduction of glucose utilisation persisted independently of insulin stimulation
      or muscle fibre type, but depended on fatty acid availability (the effect on
      glucose transport in the absence of fatty acids was an increase of 30+/-9%,
      p<0.01), suggesting a role for the glucose-fatty acid cycle. At higher
      concentrations, GW501516 uncoupled oxidative phosphorylation by direct action on
      isolated mitochondria. CONCLUSIONS/INTERPRETATION: GW501516-induced activation of
      PPAR-delta reduces glucose utilisation by skeletal muscle through a switch in
      mitochondrial substrate preference from carbohydrate to lipid. High
      concentrations of GW501516 induce mitochondrial uncoupling independently of PPAR
      delta.

PMID- 16960686
TI  - Microstructural development of human brain assessed in utero by diffusion tensor
      imaging.
AB  - BACKGROUND: Diffusion-weighted MR imaging (DWI) has been shown to be a great tool
      to assess white matter development in normal infants. Comparison of cerebral
      diffusion properties between preterm infants and fetuses of corresponding ages
      should assist in determining the impact of premature ex utero life on brain
      maturation. OBJECTIVE: To assess in utero maturation-dependent microstructural
      changes of fetal cerebral white matter using diffusion tensor MR imaging.
      MATERIALS AND METHODS: An echoplanar sequence with diffusion gradient (b=700
      s/mm(2)) applied in six non-colinear directions was performed between 31 and
      37(+3) weeks of gestation in 24 fetuses without cerebral abnormality on T1- and
      T2-weighted images. Apparent diffusion coefficient (ADC) and fractional
      anisotropy (FA) were measured in the white matter. RESULTS: Mean ADC values were
      1.8 microm(2)/ms in the centrum semiovale, 1.2 microm(2)/ms in the splenium of
      the corpus callosum and 1.1 microm(2)/ms in the pyramidal tract. The paired
      Wilcoxon rank test showed significant differences in ADC between these three
      white matter regions. Mean FA values were 1.1%, 3.8% and 4.7%, respectively, in
      the centrum semiovale, corpus callosum and pyramidal tract. A significant age
      related decrease in ADC and an increase in FA towards term were demonstrated in
      the pyramidal tract and corpus callosum. CONCLUSION: Diffusion tensor imaging in
      utero can provide a quantitative assessment of the microstructural development of
      fetal white matter. Anisotropic parameters of the diffusion tensor should improve
      with technical advances.

PMID- 16960687
TI  - RBE of 25 kV X-rays for the survival and induction of micronuclei in the human
      mammary epithelial cell line MCF-12A.
AB  - The broad application of low energy X-rays below about 50 keV in radiation
      therapy and diagnostics and especially in mammography substantiates the precise
      determination of their relative biological effectiveness (RBE). A quality factor
      of 1 is stated for photons of all energies in the International Commission on
      Radiological Protection Recommendations. However, the RBE of low-energy X-rays
      compared to high-energy photons was found to be dependent on photon energy, cell
      line and endpoints studied, hence varying from less than one up to about four. In
      the present study, the human mammary epithelial cell line MCF-12A has been chosen
      due to the implementation of the results in the estimation of risk from
      mammography procedures. The RBE of 25 kV X-rays (W anode, 0.3 mm Al filter)
      relative to 200 kV X-rays (W anode, 0.5 mm Cu filter) was determined for
      clonogenic survival in the dose range 1-10 Gy and micronuclei (MN) induction in
      the range 0.5-3.5 Gy. The RBE for clonogenic survival was found to be
      significantly higher than 1 for surviving fractions in the range 0.005<S<0.2. The
      RBE decreased with increasing survival, with an RBE0.1 at 10% survival of 1.13+/
      0.03. The effectiveness of soft X-rays for MN induction was found to be 1.40+/
      0.07 for the fraction of binuclear cells (BNC) with MN and 1.44+/-0.17 for the
      number of MN per BNC. In contrast, the RBE determined from the number of MN per
      MN-bearing BNC was found to be 1.08+/-0.32. This indicates that the effectiveness
      of 25 kV X-rays results from an increase in the number of damaged cells, which,
      however, do not have higher number of MN per cell.

PMID- 16960688
TI  - Dynamics of starvation in humans.
AB  - A differential equation model describing the dynamics of stored energy in the
      form of fat mass, lean body mass and ketone body mass during prolonged starvation
      is developed. The parameters of the model are estimated using available data for
      7 days into starvation. A simulation of energy stores for a normal individual
      with body mass index between 19 and 24 and an obese individual with body mass
      index over 30 are calculated. The length of time the obese subject can survive
      during prolonged starvation is estimated using the model.

PMID- 16960689
TI  - Consistency of estimators of population scaled parameters using composite
      likelihood.
AB  - Composite likelihood methods have become very popular for the analysis of large
      scale genomic data sets because of the computational intractability of the basic
      coalescent process and its generalizations: It is virtually impossible to
      calculate the likelihood of an observed data set spanning a large chromosomal
      region without using approximate or heuristic methods. Composite likelihood
      methods are approximate methods and, in the present article, assume the
      likelihood is written as a product of likelihoods, one for each of a number of
      smaller regions that together make up the whole region from which data is
      collected. A very general framework for neutral coalescent models is presented
      and discussed. The framework comprises many of the most popular coalescent models
      that are currently used for analysis of genetic data. Assume data is collected
      from a series of consecutive regions of equal size. Then it is shown that the
      observed data forms a stationary, ergodic process. General conditions are given
      under which the maximum composite estimator of the parameters describing the
      model (e.g. mutation rates, demographic parameters and the recombination rate) is
      a consistent estimator as the number of regions tends to infinity.

PMID- 16960690
TI  - Molecular and immunological evaluation of the expression of cancer/testis gene
      products in human colorectal cancer.
AB  - Tumor-specific gene products, such as cancer/testis (CT) antigens, constitute
      promising targets for the development of T cell vaccines. Whereas CT antigens are
      frequently expressed in melanoma, their expression in colorectal cancers (CRC)
      remains poorly characterized. Here, we have studied the expression of the CT
      antigens MAGE-A3, MAGE-A4, MAGE-A10, NY-ESO-1 and SSX2 in CRC because of the
      presence of well-described HLA-A2-restricted epitopes in their sequences. Our
      analyses of 41 primary CRC and 14 metastatic liver lesions confirmed the low
      frequency of expression of these CT antigens. No increased expression frequencies
      were observed in metastatic tumors compared to primary tumors. Histological
      analyses of CRC samples revealed heterogeneous expression of individual CT
      antigens. Finally, evidence of a naturally acquired CT antigen-specific CD8(+) T
      cell response could be demonstrated. These results show that the expression of CT
      antigens in a subset of CRC patients induces readily detectable T cell responses.

PMID- 16960691
TI  - HLA class I expression in metastatic melanoma correlates with tumor development
      during autologous vaccination.
AB  - Our knowledge of the mechanisms underlying tumor-specific immune response and
      tumor escape has considerably increased. HLA class I antigen defects remain an
      important tumor escape mechanism since they influence the interactions between
      tumor cells and specific T and NK cells in the course of malignant disease. We
      have studied here HLA class I expression in six subcutaneous metastases obtained
      from a melanoma patient immunized with an autologous melanoma cell vaccine (M
      VAX). We report in this paper that HLA class I antigen expression on these
      metastatic lesions strongly correlated with the course of the disease. The three
      metastases that were partially regressing at the time of their excision showed a
      strong HLA class I expression, whereas the progressing ones showed a very weak or
      negative staining with most of the anti-HLA class I mAbs used. Real-time
      quantitative PCR of the samples obtained from microdissected tumor tissue
      revealed a significant difference in the mRNA levels of HLA-ABC heavy chain and
      beta2m between the two types of metastases, i.e., lower levels in progressing
      metastases and high levels in regressing ones, confirming the immunohistological
      findings. This is, to our knowledge, the first report where the clinical outcome
      of different HLA class I positive and negative melanoma metastases can be clearly
      correlated with the regression and progression of the disease, respectively.

PMID- 16960692
TI  - Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T
      cells and restores T and NK effector functions in end stage cancer patients.
AB  - CD4+CD25+ regulatory T cells are involved in the prevention of autoimmune
      diseases and in tumor-induced tolerance. We previously demonstrated in tumor
      bearing rodents that one injection of cyclophosphamide could significantly
      decrease both numbers and suppressive functions of regulatory T cells,
      facilitating vaccine-induced tumor rejection. In humans, iterative low dosing of
      cyclophosphamide, referred to as "metronomic" therapy, has recently been used in
      patients with advanced chemotherapy resistant cancers with the aim of reducing
      tumor angiogenesis. Here we show that oral administration of metronomic
      cyclophosphamide in advanced cancer patients induces a profound and selective
      reduction of circulating regulatory T cells, associated with a suppression of
      their inhibitory functions on conventional T cells and NK cells leading to a
      restoration of peripheral T cell proliferation and innate killing activities.
      Therefore, metronomic regimen of cyclophosphamide does not only affect tumor
      angiogenesis but also strongly curtails immunosuppressive regulatory T cells,
      favoring a better control of tumor progression. Altogether these data support
      cyclophosphamide regimen as a valuable treatment for reducing tumor-induced
      immune tolerance before setting to work anticancer immunotherapy.

PMID- 16960693
TI  - Ii-Key/HER-2/neu(776-790) hybrid peptides induce more effective immunological
      responses over the native peptide in lymphocyte cultures from patients with HER
      2/neu+ tumors.
AB  - We have demonstrated that coupling an immunoregulatory segment of the MHC class
      II-associated invariant chain (Ii), the Ii-Key peptide, to a promiscuous MHC
      class II epitope significantly enhances its presentation to CD4+ T cells. Here, a
      series of homologous Ii-Key/HER-2/neu(776-790) hybrid peptides, varying
      systematically in the length of the epitope(s)-containing segment, are
      significantly more potent than the native peptide in assays using T cells from
      patients with various types of tumors overexpressing HER-2/neu. In particular,
      priming normal donor and patient PBMCs with Ii-Key hybrid peptides enhances
      recognition of the native peptide either pulsed onto autologous dendritic cells
      (DCs) or naturally presented by IFN-gamma-treated autologous tumor cells.
      Moreover, patient-derived CD4+ T cells primed with the hybrid peptides provide a
      significantly stronger helper effect to autologous CD8+ T cells specific for the
      HER-2/neu(435-443) CTL epitope, as illustrated by either IFN-gamma ELISPOT assays
      or specific autologous tumor cell lysis. Hybrid peptide-specific CD4+ T cells
      strongly enhanced the antitumor efficacy of HER-2/neu(435-443) peptide-specific
      CTL in the therapy of xenografted SCID mice inoculated with HER-2/neu
      overexpressing human tumor cell lines. Our data indicate that the promiscuously
      presented vaccine peptide HER-2/neu(776-790) is amenable to Ii-Key-enhancing
      effects and supports the therapeutic potential of vaccinating patients with HER
      2/neu+ tumors with such Ii-Key/HER-2/neu(776-790) hybrid peptides.

PMID- 16960695
TI  - Usefulness of magnetic resonance cholangiopancreatography in biliary structures
      in infants: a four-case report.
AB  - In this paper, we report the usefulness of magnetic resonance
      cholangiopancreatography (MRCP) in excluding biliary atresia (BA) as the cause of
      neonatal cholestasis. MRCP with a 1.5-T magnetic resonance (MR) imaging unit was
      performed on four jaundiced neonates and infants aged from 38 days to 106 days.
      The diagnosis of BA (n=2) was confirmed with surgery, liver biopsy and surgical
      cholangiography. Diagnosis of neonatal hepatitis (NH, n=2) was confirmed with
      clinical follow-up until jaundice resolved, while one of them was diagnosed with
      surgical cholangiography. In all discoloured acholic stools, increased direct
      bilirubin (4.4-11.3 mg/dl) with positive lipoprotein X prompted technetium 99mTc
      disofenin scanning, which showed no excretion. Computed tomography (CT) showed a
      gallbladder in one with hepatitis but no intrahepatic bile duct in two with BA.
      The Kasai operation was performed in two patients with BA. In two patients with
      BA, neither the common bile duct nor the common hepatic ducts were visible at
      MRCP. In two patients with NH, MRCP clearly depicted both the common hepatic and
      the common bile ducts. MRCP was accurate in excluding BA as the cause of neonatal
      cholestasis, while 99mTc disofenin cholescintigraphic findings were false
      positive in two patients with non-obstructive cholestasis. We conclude that MRCP
      can be used to depict the major biliary structures of neonates and small infants
      and to exclude BA as the cause of neonatal cholestasis by allowing visualisation
      of the biliary tract.

PMID- 16960694
TI  - Is a gene important for bone resorption a candidate for obesity? An association
      and linkage study on the RANK (receptor activator of nuclear factor-kappaB) gene
      in a large Caucasian sample.
AB  - In light of findings that osteoporosis and obesity may share some common genetic
      determination and previous reports that RANK (receptor activator of nuclear
      factor-kappaB) is expressed in skeletal muscles which are important for energy
      metabolism, we hypothesize that RANK, a gene essential for osteoclastogenesis, is
      also important for obesity. In order to test the hypothesis with solid data we
      first performed a linkage analysis around the RANK gene in 4,102 Caucasian
      subjects from 434 pedigrees, then we genotyped 19 SNPs in or around the RANK
      gene. A family-based association test (FBAT) was performed with both a
      quantitative measure of obesity [fat mass, lean mass, body mass index (BMI), and
      percentage fat mass (PFM)] and a dichotomously defined obesity phenotype-OB (OB
      if BMI > or = 30 kg/m(2)). In the linkage analysis, an empirical P = 0.004 was
      achieved at the location of the RANK gene for BMI. Family-based association
      analysis revealed significant associations of eight SNPs with at least one
      obesity-related phenotype (P < 0.05). Evidence of association was obtained at
      SNP10 (P = 0.002) and SNP16 (P = 0.001) with OB; SNP1 with fat mass (P = 0.003);
      SNP1 (P = 0.003) and SNP7 (P = 0.003) with lean mass; SNP1 (P = 0.002) and SNP7
      (P = 0.002) with BMI; SNP1 (P = 0.003), SNP4 (P = 0.007), and SNP7 (P = 0.002)
      with PFM. In order to deal with the complex multiple testing issues, we performed
      FBAT multi-marker test (FBAT-MM) to evaluate the association between all the 18
      SNPs and each obesity phenotype. The P value is 0.126 for OB, 0.033 for fat mass,
      0.021 for lean mass, 0.016 for BMI, and 0.006 for PFM. The haplotype data
      analyses provide further association evidence. In conclusion, for the first time,
      our results suggest that RANK is a novel candidate for determination of obesity.

PMID- 16960696
TI  - Zinc-deficiency dermatitis in breast-fed infants.
AB  - We report ten infants (mean gestational age: 30 weeks; range: 25 to 40 weeks)
      with zinc deficiency dermatitis who developed erosive, impetiginized
      periorificial dermatitis at 10 weeks of age (corresponding to a mean gestational
      age of 41.4 weeks, with a range of 36-44 weeks), but who were otherwise well.
      Cutaneous symptoms were initially misdiagnosed as eczema or impetigo in 8/10
      (80%) children who received either topical (4/8) and/or systemic (6/8)
      antibiotics. Topical corticosteroids were applied in 4/10 infants for a mean time
      of 4 weeks (range: 2 to 5 weeks) before the correct diagnosis was established by
      decreased serum zinc levels; skin atrophy (telangiectasia, thinning) as a
      complication of topical steroid treatment (class II steroids) was observed in two
      infants. All children responded to oral therapy with zinc sulfate or zinc
      gluconate (1.5-4 mg/kg/d). Skin lesions started to clear within 24 h after the
      initiation of therapy and had completely cleared in all infants after 14 days of
      therapy (range: 3-14 days). We conclude that nutritional zinc deficiency is a
      frequently misdiagnosed problem in thriving, fully breast-fed preterm babies. It
      is attributable to the decreased zinc content of human milk as compared to cow's
      milk, and the increased demand of zinc in rapidly thriving preterm infants. It
      seems advisable to routinely check serum zinc levels in fully breast-fed preterm
      infants who do not receive regular oral zinc supplementation once they reach a
      gestational age of 40 weeks.

PMID- 16960697
TI  - [Osteonecrosis of the jaws by long term therapy with bisphosphonates].
AB  - For several decades bisphosphonates have been used to reduce skeletal related
      events in patients with both osteoporosis or bone metastases. Under long term
      application, besides the known therapy side effects, a new clinical picture has
      been described within the last few years. This is osteonecrosis of the jaws,
      which is characterized by its difficulty in treatment. Besides exposed jaw bone,
      the start of the disease usually lacks any symptoms. The typical clinical
      symptoms then are foetor ex ore, swelling, exsudation, loosening of teeth, pain
      or paresthesia. Later oro-antral/nasal or oro-cutaneous fistula can develop. The
      X-ray shows persisting tooth sockets after extractions and later cloudy radio
      lucency, sequestra or fractures. The patient exposed to bisphosphonate can be
      grouped according to the risk for osteonecrosis: high risk patients with
      intravenous bisphosphonate therapy and additional chemo-, radiation or corticoid
      therapy--predominantly patients with a malignant underlying disease and bone
      metastases low risk patients with an oral bisphosphonate therapy without
      additional chemo-, radiation or corticoid therapy--preferably patients with non
      corticoid-induced osteoporosis. Before starting a bisphosphonate therapy possible
      causes of infection should be treated and risk of injuries to the mucosa should
      be reduced according to the individual risk profile. This is supplemented by
      information of the patient about the risk of necrosis and the possibilities for
      prevention. Regular dental recall under bisphophonate therapy is emphasised for
      early recognition of possible problems. Prophylaxis is recommended for the
      prevention of periodontal infection combined with a follow up of removable
      denture for possible ulcera. Generally, conservative treatment measures are
      preferred to surgical ones. Inevitable operations are carried out non
      traumatically using broad spectrum antibiotic prophylaxis until the day of suture
      removal (not before day 10). Long term follow up examinations are
      recommended.Patients with dental implants inserted before a bisphophonate therapy
      should be subject to intensive recall examinations. For patients undergoing or
      following a bisphosphonate therapy the indication for dental implants should be
      as strict as for patients following head and neck radiation therapy. In the
      present for patients with osteonecrosis, even after healing, dental implants are
      regarded as contra-indication. Therapy of the necrosis often requires general
      anaesthesia, hospitalisation, naso-gastral feeding tube and intravenous, systemic
      antiinfective treatment. The necrosis is removed completely and a tension free
      wound closure with vascularised tissue is intended. A literature review shows the
      metabolic effect of biphosphonates, the known pathogenesis of the bisphosphonate
      induced jaw necrosis. It is essential to develop interdisciplinary communication,
      aiming at a joint care for this group of concerned patients and involving not
      only those medical disciplines, which order and use bisphosphonates, but
      especially dentists and maxillofacial surgeons.

PMID- 16960698
TI  - Dopamine efflux in the nucleus accumbens during within-session extinction,
      outcome-dependent, and habit-based instrumental responding for food reward.
AB  - RATIONALE: Dopamine (DA) activity in the nucleus accumbens (NAc) is related to
      the general motivational effects of rewarding stimuli. Dickinson and colleagues
      have shown that initial acquisition of instrumental responding reflects action
      outcome relationships based on instrumental incentive learning, which establishes
      the value of an outcome. Given that the sensitivity of responding to outcome
      devaluation is not affected by NAc lesions, it is unlikely that incentive
      learning during the action-outcome phase is mediated by DA activity in the NAc.
      OBJECTIVES: DA efflux in the NAc after limited and extended training was compared
      on the assumption that comparable changes would be observed during both action
      outcome- and habit-based phases of instrumental responding for food. This study
      also tested the hypothesis that increase in NAc DA activity is correlated with
      instrumental responding during extinction maintained by a conditioned stimulus
      paired with food. METHODS: Rats were trained to lever press for food (random
      interval 30 s schedule). On the 5th and 16th day of training, microdialysis
      samples were collected from the NAc or mediodorsal striatum (a control site for
      generalized activity) during instrumental responding in extinction and then for
      food reward, and analyzed for DA content using high performance liquid
      chromatography. RESULTS: Increase in DA efflux in the NAc accompanied responding
      for food pellets on both days 5 and 16, with the magnitude of increase
      significantly enhanced on day 16. DA efflux was also significantly elevated
      during responding in extinction only on day 16. CONCLUSIONS: These results
      support a role for NAc DA activity in Pavlovian, but not instrumental, incentive
      learning.

PMID- 16960699
TI  - Dose-response relationship of duloxetine in placebo-controlled clinical trials in
      patients with major depressive disorder.
AB  - RATIONALE: The optimal dose for achieving the maximum antidepressive effect of
      selective serotonin reuptake inhibitors (SSRIs) or serotonin-noradrenalin
      reuptake inhibitors (SNRIs) remains a controversial issue. The varying
      sensitivity of scales that measure the severity of depression is one of the many
      factors affecting the evaluation of the dose-response relationship with
      antidepressants. OBJECTIVES: To determine if the 6-item Hamilton rating scale for
      depression (HAM-D6) demonstrates a clearer association between dose and
      antidepressive effect compared with the 17-item Hamilton rating scale for
      depression (HAM-D17) for fixed doses of duloxetine hydrochloride (40, 60, 80, and
      120 mg daily) from six double-blind, randomized, placebo-controlled clinical
      trials assessing safety and efficacy in the acute treatment of patients with DSM
      IV-defined major depressive disorder (MDD). METHODS: Mantel-Haenszel adjusted
      effect sizes were determined by dose for change from baseline to endpoint in HAM
      D6 and HAM-D17 scores from the six studies. To confirm, assessments were repeated
      on the subset of the population corresponding to the 70% of patients with the
      longest duration of treatment regardless of study, treatment, dose, geography, or
      completion status. RESULTS: For the majority of assessments, HAM-D6 effect sizes
      were numerically larger than those estimated from the HAM-D17. Findings support
      that duloxetine 60 mg daily is the best effective dose. CONCLUSIONS: In this
      assessment of patients with MDD, the HAM-D6 was shown to be more sensitive
      compared with the HAM-D17 at detecting treatment effects. These findings are
      consistent with published results of other effective antidepressants.

PMID- 16960700
TI  - Association of OPRM1 A118G variant with the relative reinforcing value of
      nicotine.
AB  - RATIONALE: The endogenous opioid system has been implicated in substance abuse
      and response to pharmacotherapies for nicotine and alcohol addiction. We examined
      (1) the association of the functional OPRM1 A118G variant with the relative
      reinforcing value of nicotine and (2) the main and interacting effects of the mu
      opioid receptor antagonist naltrexone on nicotine reinforcement. METHODS: In a
      within-subject, double-blind human laboratory study, 30 smokers of each OPRM1
      genotype (A/A vs. A/G or G/G) participated in two experimental sessions following
      4 days of orally administered naltrexone 50 mg or placebo. Participants completed
      a validated assessment of the relative reinforcing value of nicotine. This
      cigarette choice paradigm assesses self-administration of 0.6 mg nicotine vs.
      0.05 mg (denicotinized) cigarettes after a brief period of nicotine abstinence.
      RESULTS: The relative reinforcing value of nicotine (number of nicotine cigarette
      puffs) was predicted by a significant OPRM1 by gender interaction. Among women,
      the low-activity G allele (A/G and G/G) was associated with a reduced reinforcing
      value of nicotine; among male smokers, there was no association with genotype.
      Smokers carrying a G allele were also significantly less likely to differentiate
      the nicotine vs. denicotinized cigarettes by subjective ratings of satisfaction
      and strength. No evidence for an effect of naltrexone on nicotine reinforcement
      was found in the overall sample or in the genotype or gender subgroups.
      CONCLUSIONS: This study provides initial evidence for an association of the OPRM1
      A118G variant with nicotine reinforcement in women.

PMID- 16960701
TI  - Value of diffusion-weighted MR imaging in acute cervical cord injury as a
      predictor of outcome.
AB  - INTRODUCTION: We analyzed the findings of diffusion-weighted (DW) imaging using
      the single-shot fast spin-echo sequence in acute cervical cord injury and
      evaluated the usefulness of this method for predicting the prognosis. METHODS:
      Our patient group comprised 14 patients examined 2 h to 3 days after injury.
      First, we visually evaluated the DW imaging findings in all patients. Apparent
      diffusion coefficient (ADC) maps were also assessed in 13 patients. Second, we
      assessed follow-up magnetic resonance (MR) examinations obtained in six patients
      whose DW images showed hyperintensity. Third, we reviewed the functional outcome
      at discharge. RESULTS: The lesions showed hyperintensity in ten patients, and no
      abnormal signal was noted in the remaining four patients. The ADC maps showed
      restricted diffusion in all patients with hyperintensity on DW imaging except in
      one patient for whom the ADC map was unavailable. Repeated MR examinations
      obtained in six of the ten patients showed either myelomalacia or exacerbation.
      Seven of the ten patients (70%) required assistance and the other three were
      independent. Among the four patients without hyperintensity on DW imaging, three
      (75%) were independent and only one required assistance. CONCLUSION: DW imaging
      in acute cervical cord injury often reveals restricted diffusion. This finding
      may predict an unfavorable functional prognosis.

PMID- 16960703
TI  - [Emergency radiology of bowel obstruction].
AB  - Clinical radiology is a key to the management of bowel obstruction. Plain
      abdominal radiographs combined with history, clinical exam, and laboratory
      findings are essential for further individualized strategies. If the cause of
      obstruction is obvious after plain films and there is a need for emergent
      surgery, no further imaging is required. In all other cases, multislice CT with
      at least intravenous and rectal contrast is the method of choice due to its broad
      diagnostic spectrum. If CT is not available, contrast enema is recommended in
      suspected large bowel obstruction. Oral administration of water-soluble contrast
      agents has no significant value in the workup of bowel obstruction.

PMID- 16960704
TI  - Total disc arthroplasty: consequences for sagittal balance and lumbar spine
      movement.
AB  - This in vivo biomechanical study was undertaken to analyze the consequences for
      sagittal balance and lumbar spine movement in three different lumbar disc
      prostheses. A total of 105 patients underwent total disc replacement in three
      different centers. The Maverick prosthesis was used in 46 patients, the SB
      Charite device was used in 49 patients and the Prodisc device was utilized in 10
      patients. The analysis was computer assisted, using Spineview and Matlab
      softwares. The intra and inter-observer reliability and measurement uncertainty
      was performed. The analysis of lateral X-ray films in flexion-extension allowed
      to measure the prosthesis positioning, the range of motion (ROM), the
      localization of the mean center of rotation (MCR), the vertebral translation and
      the disc height, for each prosthesis device. The sagittal balance was analyzed on
      a full spine film. The parameters studied were described by Duval-Beaupere. The
      results were compared to the data found in literature, and compared to 18
      asymptomatic volunteers, and 61 asymptomatic subjects, concerning the sagittal
      balance. The prostheses allowed an improvement of the ROM of less than 2 degrees.
      The ROM of L5-S1 prostheses ranged from 11.6 to 15.6% of the total lumbar motion
      during flexion-extension. At L4-L5 level, the ROM decreased when there was an
      arthrodesis associated at the L5-S1 level. There was no difference of ROM between
      the three prostheses devices. The MCR was linked to the ROM, but did not depend
      on the prosthesis offcentering. The disc height improved for any prosthesis, and
      decreased in flexion or in extension, when the prosthesis was offcentered. An
      increase of translation indicated a minor increase of the ROM at L4-L5 level
      after Maverick or SB Charite implantation. The L5-S1 arthrodesis was linked with
      an increase of the pelvic tilt. The lumbar lordosis curvature increased between
      L4 and S1, even more when a prosthesis was placed at the L3-L4 level. Total disc
      arthroplasty is useful in the surgical management of discogenic spinal pathology.
      The three prostheses studied allowed to retorate the disc height, the ROM,
      without disrupting the sagittal balance, but induced modification of the lumbar
      curvature.

PMID- 16960708
TI  - EuroSpine 2006. 8th Annual Meeting of the European Spine Society, 25-28 October
      2006, Istanbul, Turkey. Abstracts.

PMID- 16960709
TI  - Role of routine blood cultures in detecting unapparent infections during
      continuous renal replacement therapy.
AB  - OBJECTIVE: Continuous renal replacement therapy (CRRT) is frequently employed in
      the management of renal failure in unstable intensive care patients. At some
      centers, blood cultures are performed routinely while on CRRT to monitor for
      occult bacteremia. We questioned the role of routine blood cultures (RBC) in
      diagnosing underlying infections in these often afebrile patients. DESIGN:
      Retrospective cohort study (1998-2003). SETTING: Medical, surgical and pediatric
      intensive care units in a tertiary care teaching hospital. METHODS/MEASUREMENTS:
      We undertook a retrospective chart review of all 101 episodes of CRRT performed
      in our hospital since 1998. The primary endpoint of the study was the number of
      positive cultures that changed patient management. For each positive result,
      documented infection and parameters of sepsis were noted. RESULTS: There were 101
      treatments of CRRT in 98 patients. A total of 698 routine RBC bottles were drawn,
      a mean of 7.2+/-7 per patient; of those, 29 (4%) were positive in 17patients,
      documenting 11 bacteremias. Six positive cultures represented contaminants. In
      all but one case, infection was known or signs of sepsis were present prior to
      receipt of the culture result. CONCLUSIONS: For patients on CRRT, RBC are rarely
      positive, and do not detect occult infection in the absence of clinical evidence
      of infection for the majority of patients. Because routine cultures utilize
      significant resources, and can result in false-positive results, RBC should not
      be performed in these patients. Careful clinical monitoring, with blood cultures
      performed at the first clinical suggestion of an infection, should detect all
      clinically relevant infections.

PMID- 16960710
TI  - The isoprenoid pathway in the ectomycorrhizal fungus Tuber borchii Vittad.:
      cloning and characterisation of the tbhmgr, tbfpps and tbsqs genes.
AB  - The isoprenoid pathway of the ectomycorrhizal fungus Tuber borchii Vittad is
      investigated to better understand the molecular mechanisms at work, in particular
      during the maturation of the complex ascomata (the so-called "truffles"). Three
      T. borchii genes coding for the most important regulatory enzymes of the
      isoprenoid biosynthesis, 3-hydroxy-3-methylglutaryl-CoA reductase, farnesyl
      diphosphate synthase (FPPS) and squalene synthase (SQS), were cloned and
      characterised. The analyses of their nucleotide and deduced amino acid sequences
      led us to identify the typical domains shown in homologous proteins. By using a
      quantitative real-time PCR the expression pattern of the three genes was analysed
      in the vegetative phase and during the complex ascoma maturation process,
      revealing an over-expression in the mature ascomata. The enzymatic activity of
      the T. borchii 3-hydroxy-3-methylglutaril-CoA reductase (HMGR) was investigated
      with a HPLC method, confirming that the significant isoprenoid biosynthesis in
      ripe ascomata proceeds not only via a transcriptional activation, but also via an
      enzyme activity control. These findings imply that isoprenoids play a fundamental
      role in Tuber ascomata, particularly in the last phases of their maturation, when
      they could be involved in antifungal or/and antimicrobial processes and
      contribute to the famous flavour of the truffle ascomata.

PMID- 16960712
TI  - Domperidone toxicity in an infant on maintenance haemodialysis.

PMID- 16960711
TI  - Childhood hemolytic uremic syndrome is associated with adolescent-onset diabetes
      mellitus.
AB  - Extra-renal manifestations of the hemolytic uremic syndrome in children are well
      described. Pancreatic involvement may manifest as transient hyperglycemia and
      permanent diabetes mellitus. Two previous case reports demonstrate short periods
      of "remission" between initial hyperglycemia and the development of permanent
      diabetes mellitus. We report an unusual case of a two-year-old Caucasian boy
      whose HUS-associated hyperglycemia resolved shortly after the acute phase of his
      illness only to recur as permanent diabetes mellitus at puberty. To our knowledge
      no other case is reported that demonstrates such a long interval between initial
      presentation and the development of permanent diabetes mellitus.

PMID- 16960713
TI  - Prognosis of acute renal failure in children.
AB  - Acute renal failure (ARF) is the acute loss of renal function over a period of
      hours or days. Given the poor prognosis of ARF among children, there is some
      urgency to identifying more effective prognostic indicators for detecting disease
      onset. Such indicators would help provide the means of selecting patients who
      would benefit the most from early aggressive treatment. In this study we assessed
      the etiologic and prognostic indicators of ARF, including several risk factors
      such as sepsis, respiratory distress, age, among others, in 300 children who were
      admitted to the Ali Asghar Children's Hospital, Tehran, Iran, from 1990 to 2003.
      Statistical analysis was performed using multiple regression and chi-square
      methods, and a score to determine the prognosis of ARF in children was developed.
      RESULT: Based on the results of this study the three common causes of ARF are
      acute tubular necrosis (ATN, 38%), acute glumerulonephritis (24%) and hemolytic
      uremic syndrome (24.1%). The overall mortality rate among our patients was 24.7%,
      with the highest risk group being those patients suffering from ischemic ATN. In
      addition, the correlation (p<0.0005) between the etiology and mortality rate was
      particularly high in patients with ischemic ATN. Mortality was also high (68%) in
      children younger than 2 years. Multiple regression models revealed that among
      those factors that significantly differed between the survivors and nonsurvivors,
      only the necessity of dialysis (p<0.0005), the use of mechanical ventilation
      (p=0.05) and disseminated intravascular coagulation (p=0.038) can be regarded as
      independent determinants of ARF prognosis in children.

PMID- 16960714
TI  - QTL mapping for resistance to root-knot nematodes in the M-120 RNR Upland cotton
      line (Gossypium hirsutum L.) of the Auburn 623 RNR source.
AB  - Root-knot nematodes Meloidogyne incognita (Kofoid and White) can cause severe
      yield loss in cotton (Gossypium hirsutum L.). The objectives of this study were
      to determine the inheritance and genomic location of genes conferring root-knot
      nematode resistance in M-120 RNR, a highly resistant G. hirsutum line with the
      Auburn 623 RNR source of resistance. Utilizing two interspecific F(2) populations
      developed from the same M-120 RNR by Gossypium barbadense (cv. Pima S-6) cross,
      genome-wide scanning with RFLP markers revealed a marker on Chromosome 7 and two
      on Chromosome 11 showing significant association with the resistant phenotype.
      The association was confirmed using SSR markers with the detection of a minor and
      a major dominant QTL on Chromosome 7 and 11, respectively. Combined across the
      two populations, the major QTL on Chromosome 11 Mi-C11 had a LOD score of 19.21
      (9.69 and 9.61 for Pop1 and Pop2, respectively) and accounted for 63.7% (52.6 and
      65.56% for Pop1 and Pop2, respectively) of the total phenotypic variation. The
      minor QTL locus on Chromosome 7 Mi ( 1 ) -C07 had a LOD score of 3.48 and
      accounted for 7.7% of the total phenotypic variation in the combined dataset but
      was detected in only one population. The allele from the M-120 RNR parent
      contributed to increased resistance in the Mi-C11 locus, but surprisingly, the
      Pima S-6 allele contributed to increased resistance in the Mi-C07 locus. The M
      120 RNR allele in the Mi-C11 locus, derived from the Auburn 623 RNR, is likely to
      have originated from the Clevewilt 6 cultivar. Results from this study indicated
      that the SSR marker CIR316 may replace the laborious greenhouse screening in
      breeding programs to identify genotypes resistant to M. incognita.

PMID- 16960715
TI  - QTL analysis for capsaicinoid content in Capsicum.
AB  - Pungency or "heat" found in Capsicum fruit results from the biosynthesis and
      accumulation of alkaloid compounds known as capsaicinoids in the dissepiment,
      placental tissue adjacent to the seeds. Pepper cultivars differ with respect to
      their level of pungency because of quantitative and qualitative variation in
      capsaicinoid content. We analyzed the segregation of three capsaicinoids:
      capsaicin, dihydrocapsaicin and nordihydrocapsaicin in an inter-specific cross
      between a mildly pungent Capsicum annuum 'NuMex RNaky' and the wild, highly
      pungent C. frutescens accession BG2814-6. F(3) families were analyzed in three
      trials in California and in Israel and a dense molecular map was constructed
      comprised mostly of loci defined by simple sequence repeat (SSR) markers. Six QTL
      controlling capsaicinoid content were detected on three chromosomes. One gene
      from the capsaicinoid biosynthetic pathway, BCAT, and one random fruit EST, 3A2,
      co-localized with QTL detected in this study on chromosomes 3 and 4. Because one
      confounding factor in quantitative determination of capsaicinoid is fruit size,
      fruit weight measurements were taken in two trials. Two QTL controlling fruit
      weight were detected, however, they did not co-localize with QTL detected for
      capsaicinoid content. The major contribution to the phenotypic variation of
      capsaicinoid content (24-42% of the total variation) was attributed to a digenic
      interaction between a main-effect QTL, cap7.1, and a marker located on chromosome
      2 that did not have a main effect on the trait. A second QTL, cap7.2 is likely to
      correspond to the QTL, cap, identified in a previous study as having pronounced
      influence on capsaicinoid content.

PMID- 16960716
TI  - Genetic control of oil content in oilseed rape (Brassica napus L.).
AB  - In oilseed rape (Brassica napus L.) like in most oleaginous crops, seed oil
      content is the main qualitative determinant that confers its economic value to
      the harvest. Increasing seed oil content is then still an important objective in
      oilseed rape breeding. In the objective to get better knowledge on the genetic
      determinism of seed oil content, a genetic study was undertaken in two genetic
      backgrounds. Two populations of 445 and a 242 doubled haploids (DH) derived from
      the crosses "Darmor-bzh" x "Yudal" (DY) and "Rapid" x "NSL96/25" (RNSL),
      respectively, were genotyped and evaluated for oil content in different trials.
      QTL mapping in the two populations indicate that additive effects are the main
      factors contributing to variation in oil content. A total of 14 and 10 genomic
      regions were involved in seed oil content in DY and RNSL populations,
      respectively, of which five and two were consistently revealed across the three
      trials performed for each population. Most of the QTL detected were not
      colocalised to QTL involved in flowering time. Few epistatic QTL involved regions
      that carry additive QTL in one or the other population. Only one QTL located on
      linkage group N3 was potentially common to the two populations. The comparisons
      of the QTL location in this study and in the literature showed that: (i) some of
      the QTL were more consistently revealed across different genetic backgrounds. The
      QTL on N3 was revealed in all the studies and the QTL on N1, N8 and N13 were
      revealed in three studies out of five, (ii) some of the QTL were specific to one
      genetic background with potentially some original alleles, (iii) some QTL were
      located in homeologous regions, and (iv) some of the regions carrying QTL for oil
      content in oilseed rape and in Arabidopsis could be collinear. These results show
      the possibility to combine favourable alleles at different QTL to increase seed
      oil content and to use Arabidopsis genomic data to derive markers for oilseed
      rape QTL and identify candidate genes, as well as the interest to combine
      information from different segregating populations in order to build a
      consolidated map of QTL involved in a specific trait.

PMID- 16960717
TI  - Refined mapping of the Pierce's disease resistance locus, PdR1, and Sex on an
      extended genetic map of Vitis rupestris x V. arizonica.
AB  - A framework genetic map based on genomic DNA-derived SSR, EST-derived SSR, EST
      STS and EST-RFLP markers was developed using 181 genotypes generated from D8909
      15 (female) x F8909-17 (male), the '9621' population. Both parents are half
      siblings with a common female parent, Vitis rupestris 'A. de Serres', and
      different male parents (forms of V. arizonica). A total of 542 markers were
      tested, and 237 of them were polymorphic for the female and male parents. The
      female map was developed with 159 mapped markers covering 865.0 cM with an
      average marker distance of 5.4 cM in 18 linkage groups. The male map was
      constructed with 158 mapped molecular markers covering 1055.0 cM with an average
      distance of 6.7 cM in 19 linkage groups. The consensus '9621' map covered 1154.0
      cM with 210 mapped molecular markers in 19 linkage groups, with average distance
      of 5.5 cM. Ninety-four of the 210 markers on the consensus map were new. The
      'Sex' expression locus segregated as single major gene was mapped to linkage
      group 2 on the consensus and the male map. PdR1, a major gene for resistance to
      Pierce's disease, caused by the bacterium Xylella fastidiosa, was mapped to the
      linkage group 14 between markers VMCNg3h8 and VVIN64, located 4.3 and 2.7 cM away
      from PdR1, respectively. Differences in segregation distortion of markers were
      also compared between parents, and three clusters of skewed markers were observed
      on linkage groups 6, 7 and 14.

PMID- 16960718
TI  - Identification of quantitative trait loci (QTL) for oil and protein contents and
      their relationships with other seed quality traits in Brassica juncea.
AB  - A detailed RFLP-genomic map was used to study the genetics of oil, seed and meal
      protein and sum of oil and seed/meal protein contents in a recombinant doubled
      haploid population developed by crossing black- and yellow-seeded Brassica juncea
      lines. Two yellow seed color genes (SC-B4, SC-A6) and one QTL for erucic acid
      content (E(1b)) showed pleiotropic effect for oil, protein and sum of oil and
      seed/meal protein contents. Six (O-A1, O-A6, O-A9, O-B3, O-B4, O-B5) and five (SP
      A1, SP-A9, SP-B4, SP-B6, SP-C) QTLs were significant for oil and seed protein
      contents, respectively. Tight linkage of three of these QTLs (SP-A1, SP-A9, SP
      B4, O-A1, O-A9, O-B4), with opposite effects, poses challenge to the plant
      breeders for simultaneous improvement of negatively correlated (r = -0.7**) oil
      and seed protein contents. However, one QTL for oil content (O-B3) and two for
      seed protein content (SP-B6, SP-C) were found to be unlinked, which offer the
      possibility for simultaneous improvement of these two traits. QTLs significant
      for meal protein (MP-A1, MP-A6, MP-A9, MP-B5, MP-B6) were significant at least
      for oil, seed protein or sum of oil and seed/meal protein contents (T-A6, T-A7, T
      B4, T-B5). Sum of oil and seed protein contents and sum of oil and meal protein
      contents had a perfect correlation, as well as same epistatic interactions and
      QTLs with similar additive effect. This indicates that protein in seed or meal
      has practically the same meaning for breeding purposes. Epistatic interactions
      were significant for the quality traits, and their linkage reflected association
      among the traits.

PMID- 16960719
TI  - Minimally invasive plate fixation of the tibia.
AB  - The treatment of fractures of the distal third of the tibia has evolved with the
      development of improved imaging and surgical techniques. The outcome of treatment
      using conventional fixation is poor. We report a study on indirect reduction in
      26 patients. All cases achieved radiological union and full weight bearing. The
      good to excellent results suggest that this method should be considered in
      metaphyseal fractures where intra-medullary nails are not suitable.

PMID- 16960720
TI  - Relationship of body mass index to early complications in hip replacement surgery
      : study performed at Hinchingbrooke Hospital, Orthopaedic Directorate,
      Huntingdon, Cambridgeshire.
AB  - The purpose of this study was to evaluate the relationship between body mass
      index and early complications following total hip replacements. Five hundred and
      fifty patients who underwent primary total hip replacement were recruited. All
      these patients were subjected to a pre-operative assessment and follow-up at 6
      weeks and 1 year following surgery. Any complications occurring during this
      period were recorded. Complications were grouped into systemic and local, both
      subdivided into minor and major depending on the risk involved. Fifty-six
      patients (10.2%) had an early complication following hip replacement surgery.
      Forty-four patients (8%) had a major local complication. Overall, there did seem
      to be a weak correlation between BMI and the rate of complications, with a p
      value of 0.104. A correlation was also found between the surgeon and presence of
      complications with a p value of 0.736. There is a weak correlation between BMI
      and early complications following hip replacement surgery, and there also seems
      to be a correlation between the operating surgeon and early complications, but
      this is not statistically significant.

PMID- 16960721
TI  - Effect of the CYP2D6*10 C188T polymorphism on postoperative tramadol analgesia in
      a Chinese population.
AB  - OBJECTIVE: The CYP2D6*10 allele is the most common allele with a frequency
      ranging from 51.3 to 70% and correlated with a significantly reduced metabolic
      activity in a Chinese population. The aim of the present study was to investigate
      whether the CYP2D6*10 allele has an impact on the postoperative analgesia effect
      of tramadol in Chinese patients recovering from major abdominal surgery. METHODS:
      A prospective study design was used and 70 gastric cancer patients recovering
      from gastrectomy were enrolled. After receiving a loading dose i.v., patients
      could self-administer doses of the drug combination (10 mg/ml tramadol plus 0.3
      mg/ml metoclopramide) via patient-controlled analgesia (PCA). Blood samples were
      collected after induction of anesthesia. The CYP2D6*10 C188T polymorphism was
      analyzed by means of polymerase chain reaction-based restriction fragment length
      polymorphism (PCR-RFLP). Demographic data among groups with different genotypes
      were analyzed using analysis of variance. The total consumption of tramadol
      between the three genotype groups for 48 h was compared. RESULTS: The allele
      frequency of CYP2D6*10 is 52.4%; patients were categorized into three groups
      according to the CYP2D6 genotype: patients without CYP2D6*10 (group I, n=17),
      patients heterozygous for CYP2D6*10 (group II, n=26), and patients homozygous for
      CYP2D6*10 (group III, n=20). The demographic data among the three groups were
      comparable. The total consumption of tramadol for 48 h in group III was
      significantly higher than that in groups I and II, while it did not differ
      between groups I and II. CONCLUSIONS: This study indicates that the CYP2D6*10
      allele has significant impact on analgesia with tramadol in a Chinese population.
      Pharmacogenetics may explain some of the varying responses to pain medication in
      postoperative patients.

PMID- 16960722
TI  - [Perioperative fluid management].

PMID- 16960723
TI  - [Consultation. Considerations on the practice of medical consultation].
AB  - On the theme of Linus Geisler's nine steps for a successful consultation between
      doctor and patient, the ability for self-criticism, the ability to be able to
      listen to oneself and the value of the doctor-patient relationship in the context
      of medical practice will be discussed. Subsequently, the framework of the
      consultation, the consulting room atmosphere and the complete setting of the
      consultation will be dealt with. The importance of active listening and the
      recognition of all messages, both verbal and from body language, will be
      particularly emphasized. The capability for empathy is presented as the necessary
      bridge to recognition of the feelings and inner world of the patient. Because one
      only sees what one is looking for and only recognizes what one knows, the
      recognition of typical complaints presented by patients in a consultation
      represents the "something" which must be specifically elucidated. The problems
      and symptoms which the patient brings to the doctor are surrounded by a ring of
      fears and apprehensions. For this reason it is decisive to uncover the
      accompanying cloud of fears and apprehensions with appropriate questions, to
      correctly assign the unsettling symptoms of the patient and to be able to
      correctly interpret them. As illustrated by the language of nature - the
      translation of deoxyribonucleic acid (DNA) triplets into amino acids - the
      translation of biological, psychological and social aspects of the complaints
      symptomatic into the level of diagnosis and the translation of the referential,
      social and affective meaning of the expressions used by the patient, into the
      level of the significance will be discussed. The role of the doctor here is that
      of a producer of context and a skilled translator. In the management of
      functional disorders and chronic diseases the construction of a shared reality is
      important. The therapeutic function of consultations is due to an introduction of
      metaphors as bridges - bridges to an improved understanding of the body, the self
      and the world. The role of the physician here is that of a moderator, motivator
      an accompanying person. Finally, Jaspers levels of good doctoring (natural
      science or causal level, nursing level, communicative-existential level) are
      stressed and the importance of a good patient-physician relationship for a
      patient-centered medicine is underlined.

PMID- 16960724
TI  - The management of metabolic energy storage during the life cycle of mayflies: a
      comparative field investigation of the collector-gatherer Ephemera danica and the
      scraper Rhithrogena semicolorata.
AB  - The concentration and seasonal dynamics of the major energy storage components,
      triglycerides and glycogen, were measured in two species of mayfly (Rhithrogena
      semicolorata and Ephemera danica) with contrasting life cycle strategies living
      in a small mountain stream. E. danica is a burrowing, semivoltine collector
      gatherer; R. semicolorata is univoltine and scrapes periphyton from stones. This
      is the first publication which focuses on the role of metabolic energy sources
      during the larval life span of two mayfly species until the larvae emerge.
      Although triglycerides are the major energy reserve in both species (>84% of
      total energy storage) throughout the whole larval development their seasonal
      dynamic differed considerably. In R. semicolorata the triglyceride concentration
      declined during the last weeks prior to emergence in both sexes. The same pattern
      was found in female larvae of E. danica, but not in male E. danica. It is
      suggested that females use triglycerides in the last larval stages for egg
      maturation, which is completed in the last larval instar. In male E. danica the
      triglyceride concentrations remained high until emergence, presumably due to
      their high energy demands as adults for their swarming flights. Glycogen
      concentrations did not show such a difference between species and sexes. Its
      significance as a storage substrate for energy is rather low; however,
      concentrations decreased in both species and sexes prior to emergence.

PMID- 16960725
TI  - The influence of sampling site and assay method on lactate concentration in
      response to rock climbing.
AB  - The sport of rock climbing has increased in popularity and as a focus for
      research. Previous studies have examined the physiological determinants for
      successful performance. Variation is evident between studies over lactate
      sampling sites and assay methods. The aim of this study was to examine the limits
      of agreement between the YSI 2300 analyser and the Lactate Pro for finger and ear
      capillary blood samples in a climbing context. Forty-five (31 males and 14
      females) participants volunteered to complete the climbing trial. Blood samples
      were collected simultaneously from finger and ear pre, post and 5 min post climb.
      The repeatability results indicated a good agreement across samples. Modelling
      analysis indicated the use of a -0.175 mmol l(-1) adjustment to move from Lactate
      Pro to YSI finger concentrations. To move from finger to ear concentrations,
      using the Lactate Pro, modelling analysis suggested a regression equation of Y =
      0.827x + 0.769 adjustment for pre climb samples and Y = 0.955x + 0.566 for post
      climb concentrations. To better understand the physiological demands of climbing
      further research on natural rock is required. Results from this study suggest the
      Lactate Pro and blood sampling from the ear lobe could be of benefit to future
      rock climbing field studies.

PMID- 16960726
TI  - CO2 rebreathing model in COPD: blood-to-gas equilibration.
AB  - Rebreathing in a closed system can be used to estimate mixed venous PCO2 (PvCO2)
      and cardiac output, but these estimates are affected by VA/Q heterogeneity. The
      purpose of this study was to validate a mathematical model of CO2 exchange during
      CO2 rebreathing in 29 patients with chronic obstructive pulmonary disease (COPD),
      with baseline arterial PCO2 (PaCO2) ranging from 28 to 60 mmHg. Rebreathing
      increased end-tidal PCO2 (PETCO2) by 20 mmHg over 2.2 min. This model employed
      baseline values for inspired (bag) PCO2, estimated PvCO2, distribution of
      ventilation and blood flow in one high VA/Q and one low VA/Q compartment, the
      ventilation increase and conservation of mass equations to simulate time courses
      of PICO2, PETCO2, PvCO2, and PaCO2. Measured PICO2 and PETCO2 during rebreathing
      differed by an average (SEM) of 1.4 (0.4) mmHg from simulated values. By end of
      rebreathing, predicted PvCO2 was lower than measured and predicted PaCO2,
      indicating gas to blood CO2 flux. Estimates of the ventilatory response to CO2,
      quantified as the slope (S) of the ventilation increase versus PETCO2, were
      inversely related to gas-to-blood PCO2 disequilibria due to VA/Q heterogeneity
      and buffer capacity (BC), but not airflow limitation. S may be corrected for
      these artifacts to restore S as a more valid noninvasive index of central CO2
      responsiveness. We conclude that a rebreathing model incorporating baseline VA/Q
      heterogeneity and BC can simulate gas and blood PCO2 in patients with COPD, where
      VA/Q variations are large and variable.

PMID- 16960727
TI  - DNMT1 and HDAC1 gene expression in impaired spermatogenesis and testicular
      cancer.
AB  - DNA methylation catalyzed by DNA methyltransferases (DNMTs) and histone
      deacetylation catalyzed by histone deacetylases (HDACs) play an important role
      for the regulation of gene expression during carcinogenesis and spermatogenesis.
      We therefore studied the cell-specific expression of DNMT1 and HDAC1 for the
      first time in human testicular cancer and impaired human spermatogenesis. During
      normal spermatogenesis, DNMT1 and HDAC1 were colocalized in nuclei of
      spermatogonia. While HDAC1 was additionally present in nuclei of Sertoli cells,
      DNMT1 was restricted to germ cells exhibiting a different expression pattern of
      mRNA (in pachytene spermatocytes and round spermatids) and protein (in round
      spermatids). Interestingly, in infertile patients revealing round spermatid
      maturation arrest, round spermatids lack DNMT1 protein, while pachytene
      spermatocytes became immunopositive for DNMT1. In contrast, no changes in the
      expression pattern could be observed for HDAC1. This holds true also in
      testicular tumors, where HDAC1 has been demonstrated in embryonal carcinoma,
      seminoma and teratoma. Interestingly, DNMT1 was not expressed in seminoma, but
      upregulated in embryonal carcinoma.

PMID- 16960728
TI  - [Cystitis emphysematosa--a case report].
AB  - We present a rare case of cystitis emphysematosa in an 85-year-old female patient
      in whom the typical risk factors were present: diabetes of long standing,
      neurogenic bladder and urinary infection with E.coli. Thanks to early diagnosis
      by cystoscopy and abdominal CT, after antibiotic treatment, appropriate insulin
      therapy and continuous bladder drainage the course was uneventful. The patient
      was fit to leave hospital after 14 days.

PMID- 16960729
TI  - [Pityrosporumfolliculitis (malasseziafolliculitis)].

PMID- 16960730
TI  - [Juvenile pityriasis rubra pilaris].

PMID- 16960731
TI  - [Hemiatrophia faciei progressiva (Parry-Romberg-syndrome) ].

PMID- 16960732
TI  - Fast 1H spectroscopic imaging using steady state free precession and spectral
      spatial RF pulses.
AB  - Recently, new methods for fast (1)H spectroscopic imaging based on the condition
      of steady state free precession (SSFP) were introduced to achieve a high signal
      to-noise ratio at short minimum measurement times. In this work, a major
      improvement is presented to overcome a crucial drawback in some of the former
      sequences: the lack of spatial selectivity. Good spectral selectivity at very
      high sampling efficiency can be achieved by using spectral-spatial RF pulses, and
      combined with localised shimming. Results are shown from both phantom experiments
      and in vivo studies on the rat brain acquired at 4.7 T.

PMID- 16960733
TI  - Developing a health-related quality of life instrument for childhood brain tumor
      survivors.
AB  - OBJECTS: With improved treatment, many childhood brain tumor survivors live
      through adulthood. A psychometrically sound instrument, which can capture their
      unique experiences through the lifetime, is needed. This paper documents the
      development of the Pediatric Functional Assessment of Cancer Therapy-Childhood
      Brain Tumor Survivor (PedsFACT-BrS) for use with survivors for at least 1 year
      posttreatment. METHODS: The PedsFACT-BrS was developed in two phases. In phase I,
      items were generated via interviewing 20 survivors, 20 caregivers, and 12
      clinicians/teachers. In phase II, Rasch analysis and classical test theory were
      used to evaluate the responses of 46 survivors and 46 caregivers. CONCLUSION: The
      34-item PedsFACT-BrS covers four domains: physical well-being, emotional well
      being and illness experiences, social well-being, and brain tumor-specific
      concerns. Its scalability is supported by Rasch analysis and its content validity
      and reliability is documented. It is now ready to be validated to other
      subpopulations across the disease trajectory.

PMID- 16960735
TI  - Functional expression of the gamma-isoenzyme of pig liver carboxyl esterase in
      Escherichia coli.
AB  - The previously reported functional expression of the gamma-isoenzyme of pig liver
      carboxylesterase (gamma-rPLE) in Pichia pastoris is hampered by the small amount
      of active enzyme formed. Earlier attempts for expression in Escherichia coli
      failed completely and not even inactive protein was detected. The lack of
      glycosylation ability of E. coli was ruled out as a possible reason, as it could
      be shown in this work that deglycosylated PLE also is active. Expression of gamma
      rPLE was studied using a range of E. coli strains with careful design of the
      constructs used and control of the cultivation conditions. Indeed, expression in
      E. coli strains Rosetta, Origami and Rosetta-gami was successful, but the
      majority of enzymes was present as inclusion bodies and only little soluble but
      inactive protein was detected. Denaturation and refolding of inclusion bodies
      failed. However, with the E. coli strain Origami, coexpressing the molecular
      chaperones GroEL und GroES, a functional expression of gamma-rPLE was possible.
      The recombinant enzyme was released by cell disruption and subjected to His-tag
      purification. The purified esterase had a specific activity of 92 U mg(-1)
      protein and a V (max)/K (m) value of 10.8x10(-3) min(-1) towards p-nitrophenyl
      acetate. Activity staining of native polyacrylamide gels gave a single band at
      175 kDa with esterolytic activity indicating a trimeric form of gamma-rPLE (
      approximately 60 kDa per monomer). gamma-rPLE was biochemically characterized and
      its properties were compared to the enzyme previously expressed in P. pastoris.
      pH and temperature profiles were identical and highest activity was found at pH 8
      8.5 and 60 degrees C, respectively. In the kinetic resolution of (R,S)-1-phenyl-2
      butyl acetate with esterase from both expression hosts, similar
      enantioselectivities (E=50) were found.

PMID- 16960734
TI  - Spontaneous posterior fossa hemorrhage associated with low-molecular weight
      heparin in an adolescent recently diagnosed with posterior reversible
      encephalopathy syndrome: case report and review of the literature.
AB  - BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) constitutes a
      well-described clinical entity, classically entailing characteristic edematous
      lesions on imaging studies in a patient with altered mental status, visual
      disturbances, headache, and seizures. PRES is reversible in the vast majority of
      cases, although progression to ischemia and hemorrhage has been documented.
      METHODS: We report a case of a 16-year-old male with chronic renal failure who
      developed PRES during a hypertensive crisis. The hypertension was successfully
      managed and PRES-associated symptomatology showed complete regression. However,
      approximately 2 months later, the patient returned with a spontaneous posterior
      fossa hemorrhage. Two weeks before this second admission, treatment with low
      molecular weight heparin had been initiated. The patient finally succumbed,
      despite surgical evacuation. The pertinent literature is reviewed. CONCLUSION: We
      suggest that the administration of low-molecular weight heparin in the setting of
      recent PRES might increase the risk for the development of intracranial
      hemorrhage.

PMID- 16960737
TI  - Fermentation of 1,3-propanediol by a lactate deficient mutant of Klebsiella
      oxytoca under microaerobic conditions.
AB  - Klebsiella oxytoca M5al is an excellent 1,3-propanediol (1,3-PD) producer, but
      too much lactic acid yielded greatly lessened the fermentation efficiency for 1,3
      PD. To counteract the disadvantage, four lactate deficient mutants were obtained
      by knocking out the ldhA gene of lactate dehydrogenase (LDH) of K. oxytoca M5al.
      The LDH activities of the four mutants were from 3.85 to 6.92% of the parental
      strain. The fed-batch fermentation of 1,3-PD by mutant LDH3, whose LDH activity
      is the lowest, was studied. The results showed that higher 1,3-PD concentration,
      productivity, and molar conversion rate from glycerol to 1,3-PD can be gained
      than those of the wild type strain and no lactic acid is produced under both
      anaerobic and microaerobic conditions. Sucrose fed during the fermentation
      increased the conversion and sucrose added at the beginning increased the
      productivity. In fed-batch fermentation with sucrose as cosubstrate under
      microaerobic conditions, the 1,3-PD concentration, conversion, and productivity
      were improved significantly to 83.56 g l-1, 0.62 mol mol-1, and 1.61 g l(-1) h-1,
      respectively. Furthermore, 60.11 g l(-1) 2,3-butanediol was also formed as major
      byproduct in the broth.

PMID- 16960736
TI  - One-pot synthesis of genistein from tyrosine by coincubation of genetically
      engineered Escherichia coli and Saccharomyces cerevisiae cells.
AB  - For production of genistein from N-acetylcysteamine-attached p-coumarate (p
      coumaroyl-NAC) supplemented to the medium, a chalcone synthase (CHS) gene from
      Glycyrrhiza echinata, a chalcone isomerase (CHI) gene from Pueraria lobata, and
      an isoflavone synthase (IFS) gene from G. echinata were placed under the control
      of the galactose-inducible GAL promoters in pESC vector and were introduced in
      Saccharomyces cerevisiae. When the recombinant yeast cells (0.5 g wet weight)
      were used as "enzyme bags" and incubated at 30 degrees C for 48 h in 100 ml of
      the buffer containing galactose and 1 mM (265 mg/l) p-coumaroyl-NAC, ca. 340
      microg genistein/l was produced. Another system consisting of two enzyme bags was
      also generated for the purpose of production of genistein from tyrosine. One
      enzyme bag was an Escherichia coli cell containing a phenylalanine ammonia-lyase
      gene from a yeast, a 4-coumarate/cinnamate:CoA ligase gene from the actinomycete
      Streptomyces coelicolor A3(2), the CHS gene, and the CHI gene, in addition to the
      acetyl-CoA carboxylase gene from Corynebacterium glutamicum, all of which were
      under the control of the isopropyl-beta-D-thiogalactopyranoside-inducible T7
      promoter, and thus producing (S)-naringenin from tyrosine. The other enzyme bag
      was a S. cerevisiae cell containing the IFS gene. Coincubation of the E. coli
      cells (0.5 g wet weight) and S. cerevisiae cells (0.5 g wet weight) at 26 degrees
      C for 60 h in 20 ml of the buffer containing 3 mM (543 mg/l) tyrosine as the
      starting substrate yielded ca. 6 mg genistein/l.

PMID- 16960739
TI  - Structural correlates of increased adhesive efficiency with adult size in the toe
      pads of hylid tree frogs.
AB  - Tree frogs are able to climb smooth, vertical substrates using specialised toe
      pads which adhere via an area-based wet adhesive mechanism. Although the link
      between pads and arboreality in frogs is well-established, few studies have
      investigated the influence of morphology on adhesion. Trinidadian tree frogs from
      the genus Hyla are geometrically similar. There is a tendency towards
      comparatively reduced mass in larger species, but toe pad area increases as
      expected with isometry. As adhesion is area-dependent, forces are affected
      directly by the increase in mass relative to pad area, and there is a decrease in
      the ability of larger species to adhere to smooth rotation platforms. However,
      there is an increase in force per unit area that suggests larger species have
      more efficient toe pads. Toe pad structure is very similar though there are
      variations in the details of a number of features. Crucially, although
      differences in morphology appeared small they had demonstrable effects on
      adhesive efficiency of the pads. Epithelial cell area correlates positively with
      frog length and adhesive efficiency, related features of cell density and
      intercellular channel length correlate negatively. These findings are discussed
      in relation to the different forces involved in the tree frogs' wet adhesive
      system.

PMID- 16960738
TI  - Physiological-biochemical properties and the ability to synthesize
      polyhydroxyalkanoates of the glucose-utilizing strain of the hydrogen bacterium
      Ralstonia eutropha B8562.
AB  - Physiological-biochemical, genetic, and cultural properties of the glucose
      utilizing mutant strain Ralstonia eutropha B8562 have been compared with those of
      its parent strain R. eutropha B5786. It has been shown that growth
      characteristics of the strain cultured on glucose as the sole carbon and energy
      source are comparable with those of the parent strain. Strain B8562 is
      characterized by high polyhydroxyalkanoate (PHA) yields on different carbon
      sources (CO(2), fructose, and glucose). PHA accumulation in the strain batch
      cultured on glucose under nitrogen deficiency reaches 90 %. The major monomer in
      the PHA is beta-hydroxybutyric acid (more than 99 mol %); the identified minor
      components are beta-hydroxyvaleric acid (0.25-0.72 mol %) and beta
      hydroxyhexanoic acid (0.08-1.5 mol %). The strain is a promising PHA producer on
      available sugar-containing media with glucose.

PMID- 16960740
TI  - Full arthroscopic inlay reconstruction of posterior cruciate ligament.
AB  - We report a full arthroscopic inlay reconstruction technique to avoid the
      morbidity of traditional open inlay procedure. With the transeptal approach a
      trough is created arthroscopically at the anatomical tibial insertion of the PCL,
      which must fit with the patellar bone block of a quadriceps tendon autograft. The
      bone plug is harvested with two nonabsorbable sutures, each end of which is
      passed through two holes from the cortical to the cancellous side. The graft is
      introduced into the knee joint from the posteromedial portal using two traction
      sutures passed previously through two transtibial tunnels exiting at the middle
      of the trough. Tibial graft fixation is achieved using the sutures knotted at the
      anterior aspect of the tibial cortex. Arthroscopic inlay procedure may be a
      rational surgical alternative because it reduces the crucial steps of an open
      inlay procedure, such as extensive exposure of the posterior capsule, the need of
      position change with risk of contamination, longer surgical time, and the risk of
      bone block fracture if an autograft is harvested. The arthroscopic procedure may
      also be performed also when hardware presence of previous surgery limits use of
      the open technique. We initially limited use of this technique to patients: (1)
      undergoing PCL revision surgery, (2) having hardware from previous tibial
      surgery, and (3) presenting a PCL lesion following posterior dislocation with
      previous vascular surgery. The results have been good, and we are now also using
      this technique for primary PCL reconstruction with favorable results.

PMID- 16960741
TI  - Sclerosing polidocanol injections in chronic painful tennis elbow-promising
      results in a pilot study.
AB  - Sclerosing polidocanol injections targeting the area with neovessels
      (vascularity) have been demonstrated to give promising clinical results in
      patients with chronic painful Achilles and patellar tendinosis. Recently, we
      demonstrated vascularity in the extensor origin in patients with chronic painful
      tennis elbow, but not in controls with pain-free elbows. In this pilot study, 11
      patients (four men and seven women, mean age 46 years) with the diagnosis of
      tennis elbow in altogether 13 elbows, were included. All patients had a long
      duration of pain symptoms (mean 23 months), and ultrasonography (US) + colour
      Doppler (CD) examination showed structural tendon changes with hypo-echoic areas,
      and a vascularity, corresponding to the painful area in the extensor origin. All
      patients were treated with US- and CD-guided injections of the sclerosing
      substance polidocanol, targeting the area with vascularity. At 8-month follow-up
      after treatment, there was a good clinical result in 11/13 elbows. Extensor
      origin pain during wrist loading activities (recorded on a VAS-scale) was
      significantly reduced (mean VAS from 75 to 34; P < 0.003), and maximal grip
      strength was significantly increased (from 29 to 40 kg; P < 0.025). Our findings
      indicate that one treatment with sclerosing polidocanol injections, targeting the
      area with vascularity in the extensor origin, has a potential to reduce the
      tendon pain and increase grip strength, in patients with chronic painful tennis
      elbow.

PMID- 16960743
TI  - A non-invasive study of alterations of the carotid artery with age using
      ultrasound images.
AB  - A region-based method for measurement of arterial diameter to find out the
      elasticity of the vessel is proposed in this paper. Arterial segments are studied
      by using images obtained through ultrasound scanning in B-mode. Pulsatile changes
      of the common carotid artery during diastole and systole are computed. To achieve
      this, thinned segmentation is done by suitably adjusting the contrast of the
      image. The diameter changes of the artery wall from the centre of artery are
      calculated. Fifty-three normal subjects with age group 20-40 years are taken for
      measurement. Measured diameter is plotted as a graph and pulsatile changes of the
      artery are obtained. Since no atherosclerotic lesions are detected in the studied
      subjects, it is suggested that the common carotid artery is a highly compliant
      artery with a strong alteration of viscoelastic properties with age.

PMID- 16960742
TI  - Reliability and accuracy of heart rate variability metrics versus ECG segment
      duration.
AB  - Despite the exponential growth in heart rate variability (HRV) research, the
      reproducibility and reliability of HRV metrics continues to be debated. We
      estimated the reliability of 11 metrics calculated from 5 min records. We also
      compared the accuracy of the HRV metrics calculated from ECG records spanning 10
      s to 10 min as compared with the metrics calculated from 5 min records. The mean
      heart rate was more reproducible and could be more accurately estimated from very
      short segments (<1 min) than any of the other HRV metrics. HRV metrics that
      effectively highpass filter the R-R interval series were more reliable than the
      other metrics and could be more accurately estimated from very short segments.
      This indicates that most of the HRV is caused by drift and nonstationary effects.
      Metrics that are sensitive to low frequency components of HRV have poor
      repeatability and cannot be estimated accurately from short segments (<10 min).

PMID- 16960744
TI  - Neural network-based diagnostic and prognostic estimations in breast cancer
      microscopic instances.
AB  - This paper deals with breast cancer diagnostic and prognostic estimations
      employing neural networks over the Wisconsin Breast Cancer datasets, which
      consist of measurements taken from breast cancer microscopic instances. A
      probabilistic approach is dedicated to solve the diagnosis problem, detecting
      malignancy among instances derived from the Fine Needle Aspirate test, while
      regression algorithms estimate the time interval that possibly correspond to the
      right end-point of the patients' disease-free survival time or the time where the
      tumour recurs (time-to-recur). For the diagnosis problem, the accuracy of the
      neural network in terms of sensitivity and specificity was measured at 98.6 and
      97.5% respectively, using the leave-one-out test method. As far as the prognosis
      problem is concerned, the accuracy of the neural network was measured through a
      stratified tenfold cross-validation approach. Sensitivity ranged between 80.5 and
      91.8%, while specificity ranged between 91.9 and 97.9%, depending on the tested
      fold and the partition of the predicted period. The prognostic recurrence
      predictions were then further evaluated using survival analysis and compared with
      other techniques found in literature.

PMID- 16960745
TI  - Vibrational analysis of mandible trauma: experimental and numerical approaches.
AB  - The aim of this study was to evaluate the effectiveness of vibrational assessment
      of the mandible fracture patterns. Measurement of natural frequencies and
      associated vibrational mode shapes was performed to determine the relationship
      between the dynamic behavior of the human mandible and incidence of mandibular
      fractures using both in vitro modal testing and finite element analysis. Our
      results show that the natural frequencies of the human mandible in dry and wet
      conditions are 567 Hz and 501 Hz, respectively. The first vibrational mode of
      human mandible is a bending vibration with nodes located at the mandibular body
      where bone fracture is less likely to occur. By contrast, high vibration
      amplitudes were identified in the symphysis/parasymphysis and subcondyle regions
      where bone fractures tend occur. These findings indicate that the vibrational
      characteristics of the mandible are potential parameters for assessment of the
      mechanisms of injury.

PMID- 16960746
TI  - Osteoarthritis severity of the hip by computer-aided grading of radiographic
      images.
AB  - A computer-aided classification system was developed for the assessment of the
      severity of hip osteoarthritis (OA). Sixty-four radiographic images of normal and
      osteoarthritic hips were digitized and enhanced. Employing the Kellgren and
      Lawrence scale, the hips were grouped by three experienced orthopaedists into
      three OA-severity categories: Normal, Mild/Moderate and Severe. Utilizing custom
      developed software, 64 ROIs corresponding to the radiographic Hip Joint Spaces
      were manually segmented and novel textural features were generated. These
      features were used in the design of a two-level classification scheme for
      characterizing hips as normal or osteoarthritic (1st level) and as of
      Mild/Moderate or Severe OA (2nd level). At each classification level, an ensemble
      of three classifiers was implemented. The proposed classification scheme
      discriminated correctly all normal hips from osteoarthritic hips (100% accuracy),
      while the discrimination accuracy between Mild/Moderate and Severe osteoarthritic
      hips was 95.7%. The proposed system could be used as a diagnosis decision
      supporting tool.

PMID- 16960747
TI  - Soft tissue modelling through autowaves for surgery simulation.
AB  - Modelling of soft tissue deformation is of great importance to virtual reality
      based surgery simulation. This paper presents a new methodology for simulation of
      soft tissue deformation by drawing an analogy between autowaves and soft tissue
      deformation. The potential energy stored in a soft tissue as a result of a
      deformation caused by an external force is propagated among mass points of the
      soft tissue by non-linear autowaves. The novelty of the methodology is that (i)
      autowave techniques are established to describe the potential energy distribution
      of a deformation for extrapolating internal forces, and (ii) non-linear materials
      are modelled with non-linear autowaves other than geometric non-linearity.
      Integration with a haptic device has been achieved to simulate soft tissue
      deformation with force feedback. The proposed methodology not only deals with
      large-range deformations, but also accommodates isotropic, anisotropic and
      inhomogeneous materials by simply changing diffusion coefficients.

PMID- 16960748
TI  - Asymmetric time-dependent model for the dynamic finger arterial pressure-volume
      relationship.
AB  - The volumetric pulses in the finger PPG signal appear as an information source
      for several indirect measurement methods. In this study we modelled
      transformation of pressure pulses into volume pulses in a wide transmural
      pressure range. The noninvasive finger arterial pressure and
      photoplethysmographic (PPG) signals were simultaneously registered in 13 healthy
      subjects while the pressure in the PPG cuff ramped up and down. The nonlinearity
      of the pressure-volume (P-V) relationship was modelled by an asymmetric function,
      consisting of two arctangents, each for a different pressure region. The time
      dependency was described by the first order lag. The disturbing effect of slow
      creeps in the PPG signal was suppressed by an equal filtering of the measured and
      model-predicted signal. The differences between the two estimates of the
      subject's P-V relationship for the increasing and decreasing cuff pressure were
      small thus showing the repeatability of this method, which can be used for the
      characterization of individual finger arterial behaviour as well as its changes.

PMID- 16960749
TI  - Childbearing after TVT: how I have my baby when I have a TVT.

PMID- 16960750
TI  - Brazilian version of the QLQ-LC13 lung cancer module of the European Organization
      for Research and Treatment of Cancer: preliminary reliability and validity
      report.
AB  - This study reports the reliability and validity of the Brazilian Portuguese
      version of QLQ-LC13. After translation and cross-cultural adaptation, the
      questionnaire was administered, together with the QLQ-C30 core questionnaire, to
      82 patients with lung cancer. The analysis was based on 60 patients who completed
      two interviews, and who received chemotherapy alone or in combination with
      radiotherapy. The reliability or internal consistency of dyspnea scale was 0.79.
      The pain scale needed to be combined with the QLQ-C30 pain items to reach a
      satisfactory value of 0.73. The construct validity was supported by the ability
      of the questionnaire to discriminate patients regarding their performance status
      and type of treatment. However, the change over time, although in the expected
      direction for all items, was statistically significant in four of the 10 items
      studied. The criterion-related validity was supported by the statistically
      significant correlation between all four side effect items and the physicians'
      reports of toxicity, while the evolutive changes in the performance status were
      statistically significant in only four items. Most psychometric properties of the
      Brazilian version of the QLQ-LC13 were adequately supported in this analysis.
      However, a wider utilization of this module is necessary to fully ascertain its
      reliability and validity properties.

PMID- 16960751
TI  - The impact of 29 chronic conditions on health-related quality of life: a general
      population survey in Finland using 15D and EQ-5D.
AB  - BACKGROUND: Health-related quality of life (HRQoL) is an essential outcome of
      health care, but there is no gold standard of HRQoL measurement. We investigated
      the impact of major chronic conditions on HRQoL using 15D and EQ-5D in a
      representative sample of Finns. METHODS: Information on chronic somatic
      conditions was obtained by interviews. Psychiatric disorders were diagnosed using
      a structured interview (M-CIDI). Tobit and CLAD regression analysis was used to
      estimate the impact of conditions on HRQoL at the individual and population
      level. MAIN RESULTS: Adjusted for other conditions and sociodemographic
      variables, Parkinson's disease had the largest negative impact on HRQoL at the
      individual level, followed by anxiety disorders, depressive disorders and
      arthrosis of the hip and knee. Based on prevalence, arthrosis of the hip or knee,
      depression, back problems and urinary incontinence caused the greatest loss of
      HRQoL at the population level. The results obtained with the two HRQoL measures
      differed markedly for some conditions and the EQ-5D results also varied with the
      regression method used. CONCLUSIONS: Musculoskeletal disorders are associated
      with largest losses of HRQoL in the Finnish population, followed by psychiatric
      conditions. Different HRQoL measures may systematically emphasize different
      conditions.

PMID- 16960752
TI  - Parents' global rating of mental health correlates with SF-36 scores and health
      services satisfaction.
AB  - BACKGROUND: Patient satisfaction surveys are often used to measure quality of
      care. However, patient satisfaction may not be a reliable indicator of service
      quality because satisfaction can be influenced by clients' characteristics such
      as their health status. METHODS: Parents of children attending a pediatric
      neurology clinic completed the Short Form Health Survey (SF-36) and global
      ratings of their physical and mental health. They also completed the Client
      Satisfaction Questionnaire (CSQ), the Measure of Processes of Care (MPOC), and
      the Family-Centered Care Survey (FCCS). RESULTS: 104 parents completed the
      survey. The correlation between the global rating of physical or mental health
      and their corresponding SF-36 scores was high. The majority (88%) of parents were
      satisfied, with a median CSQ score of 28 (IQR, 24 to 31) and a FCCS score of 4.7
      (IQR, 4.2 to 4.9). Logistic regression identified parents' mental health as a
      significant predictor of client satisfaction (OR, 1.07; 95% CI, 1.01 to 1.14).
      CONCLUSIONS: Given the positive association between parents' mental health and
      satisfaction with care, it is important to consider mental status as a covariate
      in interpreting satisfaction surveys. Parents' global rating of mental health
      appears to be a reasonable indicator of their SF-36 mental scores.

PMID- 16960753
TI  - Neurophysiological identification of position-induced neurologic injury during
      anterior cervical spine surgery.
AB  - This study was a retrospective review of 3,806 patients who underwent anterior
      cervical spine surgery with multi-modality neurophysiological monitoring
      consisting of transcranial electric motor evoked potentials, somatosensory evoked
      potentials and spontaneous electromyography between 1999-2003. The objectives of
      this study were twofold: (1) to evaluate the role of transcranial electric motor
      evoked potential tceMEP and ulnar nerve somatosensory evoked potential (SSEP)
      monitoring for identifying impending position-related stretch brachial
      plexopathy, peripheral nerve entrapment/compression or spinal cord compression
      and (2) to estimate the point-prevalence of impending neurologic injury secondary
      to surgical positioning effects. Sixty-nine of 3,806 patients (1.8% showed
      intraoperative evidence of impending neurologic injury secondary to positioning,
      prompting interventional repositioning of the patient. The brachial plexus was
      the site of evolving injury in 65% of these 69 cases. Impending brachial
      plexopathy was most commonly noted immediately following shoulder taping and the
      application of counter-traction. Brachial plexus stretch upon neck extension for
      optimal surgical access and visualization was second in frequency-of-occurrence.
      Evolving traction injury to the ulnar nerve attributed to tightly-wrapped or
      malpositioned arms was observed in 16% of alerted cases, whereas evolving spinal
      cord injury following neck extension accounted for an additional 19%. This study
      highlights the role of tceMEP and ulnar nerve SSEP monitoring for detecting
      emerging peripheral nerve injury secondary to positioning in preparation for and
      during anterior cervical spine surgery.

PMID- 16960754
TI  - Assessment of pulmonary valve and right ventricular outflow tract with real-time
      three-dimensional echocardiography.
AB  - AIM: Assessment of pulmonary valve (PV) and right ventricular outflow tract
      (RVOT) using real-time 3-dimensional echocardiography (RT3DE). METHODS: Two
      dimensional echocardiography (2DE) and RT3DE were performed in 50 patients with
      congenital heart disease (mean age 32 +/- 9.5 years, 60% female). Measurements
      were obtained at parasternal views: short axis (PSAX) at aortic valve level and
      long axis (PLAX) with superior tilting. RT3DE visualization was evaluated by 4
      point score (1: not visualized, 2: inadequate, 3: sufficient, and 4: excellent).
      Diameters of PV annulus (PVAD), and RVOT (RVOTD) were measured by both 2DE and
      RT3DE, while areas (PVAA) and (RVOTA) by RT3DE only. RESULTS: By RT3DE, PV was
      visualized sufficiently in 68% and RVOT excellently in 40%. PVAD and PVAA were
      measured in 88%. RVOTD and PVAD by 2DE at PLAX were significantly higher than
      PSAX (P < 0.0001) and lower than that by RT3DE (P < 0.001). CONCLUSION: RT3DE
      helps in RVOT and PV assessment adding more details supplemental to 2DE.

PMID- 16960755
TI  - Effects of thiazolidinediones on stroke recovery: a case-matched controlled
      study.
AB  - BACKGROUND AND PURPOSE: Anti-inflammatory therapy decreases infarct size and
      enhances stroke recovery. Thiazolidinedione peroxisome proliferator-activated
      receptor (PPAR)gamma agonists have potent anti-inflammatory and insulin
      sensitizing anti-diabetic actions. METHODS: Thirty stroke patients with type 2
      diabetes admitted for acute inpatient stroke rehabilitation receiving
      pioglitazone or rosiglitazone were matched for age, sex, initial FIM(TM) score
      and interval post-stroke with 30 stroke patients with type 2 diabetes not
      receiving thiazolidinediones. Relevant outcome variables were compared for both
      groups. RESULTS: The thiazolidinedione treated group showed significantly greater
      mean improvement in FIM(TM) score compared to control group (25.6 +/- 10.2 SD vs.
      19.8 +/- 10.5, respectively, P = 0.015). There was no significant difference in
      length of rehabilitation hospital stay (24.2 +/- 7.6 vs. 25.1 +/- 7.4 days, P =
      0.657) or final discharge destination (home/institution, 19/11 versus 17/13, P =
      0.792). CONCLUSIONS: Use of thiazolidinediones was associated with enhanced
      functional recovery in stroke patients with type 2 diabetes.

PMID- 16960756
TI  - Neurocognitive consequences of surgically corrected congenital heart defects: A
      review.
AB  - With advances in surgical procedures, neuropsychological assessment after
      congenital heart defects and pre, peri- and/or postoperative predictors of
      adverse outcome has become an important focus in research. We aim to summarize
      neuropsychological sequelae associated with different types of congenital heart
      defects, critically review the methodology used in more than 20 empirical studies
      that were retrieved from biomedical electronic search engines, and identify
      possible directions for future research. Despite the lack of adequate control
      groups and long-term studies, there seem to be some cognitive deficits. The
      largest group of children with isolated congenital heart defects present with
      normal intellectual capacities. However, they tend to show language deficits and
      motor dysfunction. Although performances on memory tasks are good, unambiguous
      conclusions concerning their attentional and executive functioning are still
      lacking. Serious behavioral problems are not an issue. In addition to a detailed
      description of the (neuro) psychological consequences of pediatric cardiac
      surgery, an overview of the predictors of the cognitive defects is provided.

PMID- 16960757
TI  - Wnt signaling and osteoblastogenesis.
AB  - Wnts are a large family of growth factors that mediate fundamental biological
      processes like embryogenesis, organogenesis and tumorigenesis. These proteins
      bind to a membrane receptor complex comprised of a frizzled (FZD) G-protein
      coupled receptor (GPCRs) and a low-density lipoprotein (LDL) receptor-related
      protein (LRP). The formation of this ligand-receptor complex initiates a number
      of intracellular signaling cascades that includes the canonical/beta-catenin
      pathway, as well as several GPCR-mediated noncanonical pathways. In recent years,
      canonical Wnt signaling has been shown to play a substantial role in the control
      of bone formation. Clinical investigations have found that mutations in LRP-5 are
      associated with bone mineral density and fractures. For example, loss-of-function
      mutations in LRP-5 cause osteoporosis pseudoglioma syndrome, while gain-of
      function mutations lead to high bone mass phenotypes. Studies of knockout and
      transgenic mouse models for Wnt pathway components like Wnt-10b, LRP-5/6,
      secreted frizzled-related protein-1, dickkopf-2, Axin-2 and beta-catenin have
      demonstrated that canonical signaling modulates most aspects of osteoblast
      physiology including proliferation, differentiation, bone matrix
      formation/mineralization and apoptosis as well as coupling to osteoclastogenesis
      and bone resorption. Future studies in this rapidly growing area of research
      should focus on elucidating Wnt/FZD specificity in the control of bone cell
      function, the role of noncanonical pathways in skeletal remodeling, and direct
      effects of Wnts on cells of the osteoclast lineage.

PMID- 16960759
TI  - Conditional optimal spacing in exponential distribution.
AB  - In this paper, we propose the conditional optimal spacing defined as the optimal
      spacing after specifying a predetermined order statistic. If we specify a
      censoring time, then the optimal inspection times for grouped inspection can be
      determined from this conditional optimal spacing. We take an example of
      exponential distribution, and provide a simple method of finding the conditional
      optimal spacing.

PMID- 16960758
TI  - Perceived spouse responses to pain: the level of agreement in couple dyads and
      the role of catastrophizing, marital satisfaction, and depression.
AB  - The primary objective of this study was to examine whether individuals with
      chronic pain ("participants") and their spouses agree on perceptions of
      solicitous, distracting, and punishing spouse responses to pain. The second aim
      was to examine the role of participant catastrophizing (a negative mental set
      about pain), participant and spouse marital satisfaction, and participant and
      spouse depression in participant perceptions of spouse responses, spouse
      perceptions of their responses, and agreement between participants and spouses.
      Individuals with chronic musculoskeletal pain and their spouses (N=108 couples)
      completed questionnaire packets. Examination of overall group averages
      (participants vs. spouses) indicated little or no differences between participant
      and spouse ratings. Examination of individual agreement in participant and spouse
      ratings indicated substantial disagreement. The proposed moderators predicted
      both participant and spouse perceptions and jointly made minor contributions to
      dyad agreement. Although neither participant nor spouse perceptions of spouse
      responses are necessarily a reflection of actual behavior, the lack of agreement
      in this study suggests it may not be valid to use only patient perceptions in
      research related to spouse responses.

PMID- 16960760
TI  - A right ventricular pressure waveform based pulse contour cardiac output
      algorithm in canines.
AB  - Tracking changes in stroke volume or cardiac output (CO) can be useful in the
      diagnosis and treatment of various cardiac illnesses. Existing arterial pressure
      waveform based pulse contour CO algorithms perform poorly during altered systemic
      hemodynamics. In this study, a right ventricular pressure waveform based pulse
      contour CO algorithm was developed to estimate the amplitude and duration of a
      hypothetical triangular flow waveform in the pulmonary artery. This algorithm was
      tested against gold standard blood flow measurements in ten canines during acute
      perturbations to preload (inferior vena caval occlusion (IVCO), rapid saline
      infusion), afterload (descending aortic occlusion (DAO), serotonin, angiotensin
      II, sodium nitroprusside infusion), and cardiac contractility (dobutamine and
      propranolol infusion). The algorithm correctly predicted the changes in CO (r2 =
      0.82) that varied from - 45 to 31% of the baseline levels. To explain this
      finding both the pulmonary arterial (PA) and the ascending aortic (AA) input
      impedances were modeled as three element windkessels. In the AA the peripheral
      resistance (from - 61 to 191%), characteristic impedance (from - 59 to 20%) and
      total arterial compliance (from - 49 to 34%) varied significantly with these
      perturbations. In contrast, these parameters in the PA changed little. In
      particular, except serotonin infusion, the characteristic impedance of the PA
      deviated only 6% (SD/mean) from baseline values. This suggests right ventricular
      pressure waveform based estimate of CO is possible during acute changes in left
      ventricular hemodynamics.

PMID- 16960761
TI  - Leukocyte-endothelium interaction: measurement by laser tweezers force
      spectroscopy.
AB  - Leukocyte adhesion to vascular endothelium is an initial step of many
      inflammatory diseases. Although the atomic force microscopy (AFM) measurements of
      leukocyte-endothelial interaction have been recently introduced. with cell
      adhesion force unbinding curves (CAFUC). We obtained pico-Newton force in the
      initial interaction between a single living THP-1 cell and HUVEC monolayer using
      a custom-built laser tweezers (LT) system. The measured quantities included the
      non-linear force-distance relationship, and the effect of yielding in cell
      detachment. It is possible to introduce a time scale into the LT cell-detachment
      experiments for further exploration and more detailed information on the
      viscoelastic properties of living cells.

PMID- 16960762
TI  - Dr. Down and "developmental disorders".

PMID- 16960764
TI  - [Social status and health].

PMID- 16960763
TI  - Ureteral fibroepithelial polyp diagnosed preoperatively on virtual CT
      ureteroscopy.
AB  - We report a 28-year-old man who presented with hematuria and intermittent flank
      pain. Conventional CT urography showed mild left hydronephrosis and an
      undetermined lesion in the left ureter. By virtual CT ureteroscopy, a
      fibroepithelial polyp (FEP) was preoperatively diagnosed. The patient had
      segmental resection of the ureter and pathological proof of FEP was obtained.

PMID- 16960765
TI  - ["Are rich people healthier?"--Representative epidemiological data on
      socioeconomic group-specific disease prevalences among adults in Germany].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to determine representative
      nationwide data on differences in the prevalence of specific diseases between
      socioeconomic groups. METHODS: The "First National Health Survey for the Federal
      Republic of Germany" was conducted from October 1997 to March 1999 in the form of
      a standardized cross-sectional questionnaire study. The data were elicited about
      the 35 most common diseases and socioeconomic status. The net sample was made up
      of a total of 7125 persons aged 18 to 79. RESULTS: A significantly higher
      prevalence in subjects of lower socioeconomic status was identified for typical
      orthopaedic diseases as well as for hypertension, chronic bronchitis, gastric and
      vascular disease. The most apparent socioeconomic difference to the detriment of
      socially deprived subjects was identified for addiction disease and diabetes. In
      contrast, numerous allergic diseases such as food allergies, urticaria, and
      allergic diseases of the respiratory tract and eyes were approximately twice as
      common among members of higher socioeconomic groups. Various gastrointestinal and
      renal diseases (hepatitis, gastritis, pyelonephritis) were also more common in
      higher socioeconomic groups. These socioeconomic differences were still apparent
      after adjustment for age and gender. CONCLUSION: This study provides
      representative socioeconomic group-specific prevalence data on a total of 35
      clinical entities for the Federal Republic of Germany. Although the self
      reporting involved in large epidemiological studies of this kind is associated
      with a certain amount of bias, it is nonetheless clear that the frequently cited
      "socioeconomic gradient", i. e., a higher disease prevalence among lower
      socioeconomic groups, seems not to apply for numerous disease entities; for which
      the association seems to be in the opposite direction. This phenomenon requires
      explanation.

PMID- 16960766
TI  - [How are quality-adjusted life years defined in German studies?].
AB  - BACKGROUND AND OBJECTIVE: Cost-utility analysis, a way of evaluating health
      economic data, is of increasing importance in Germany. It was the aim of this
      study to provide a systematic survey of all published cost-utility studies on the
      German health system. In addition to collecting general study characteristics,
      particular attention was paid to three questions: (1) On what populations are the
      utility values based that are necessary for calculating quality-adjusted life
      years (QALYs); (2) by what method were the data generated; and (3) how was the
      construction of the health-related results documented? METHODS: In the course of
      systematically reviewing all German health-economic evaluations, cost-utility
      studies published between 1990 and 2004 were identified. For this purpose both
      generic and specific health-economic databanks were searched using clearly
      defined criteria. The fulfillment of explicit criteria for inclusion and
      exclusion were tested and relevant items of information extracted from the full
      text. RESULTS: Among 730 studies for which the full text was analysed 18 cost
      utility studies were identified. Most of them were in medical journals in English
      and their objective was to evaluate curative medical interventions. The methods
      used for generating utility values differed greatly between them and in general
      were inadequately documented. CONCLUSION: Most cost-utility studies combine
      utility values that were generated from different perspectives and countries of
      origin. In addition they used different methods of assessment. As a rule the
      methods for determining utility values were not transparent and inadequately
      documented. The calculations of QALYs based on these studies are not comparable.
      Most of the studies cannot be assumed to reflect the utility of medical care in
      respect to German patients or the German population.

PMID- 16960769
TI  - [IgE-mediated allergic airway diseases].

PMID- 16960767
TI  - [Successful management of malaria tropica with 50% parasitaemia].
AB  - HISTORY: A 52-year-old woman was hospitalized with fever after a 3-week stay in
      tropical Kenya. Prophylaxis against malaria had been carried out with
      chloroquine. DIAGNOSIS: Falciparum malaria with 28% parasitaemia at first
      examination, rising to 50% after 3 hours. TREATMENT AND COURSE: Treatment with
      quinine dihydrochloride i.v. was initiated immediately after diagnosis. In
      addition, in view of increasing parasitemia of up to 50%, a partial exchange
      blood transfusion was carried out. No clinical signs of organ damage caused by
      malaria were observed. Because of a drop in blood pressure the patient needed
      catecholamine treatment for a short time. After decrease of the parasitemia the
      patient rapidly recovered and complete cure was achieved. CONCLUSION: Despite
      extremely high parasitemia the clinical signs were unusually mild. Standard
      treatment for severe malaria is intravenous administration of quinine. However,
      this drug is no longer sold in Germany, so that difficulty in obtaining it must
      be expected. A stockpiling of quinine is recommended for hospitals treating
      patients with malaria. Transfusion may improve outcome and must be considered if
      parasite counts are high or if there are clinical signs of malaria complications.

PMID- 16960770
TI  - [Sudden cardiac death due to primary cardiac ion-channel diseases].

PMID- 16960771
TI  - [Which method for the determination of creatinine?].

PMID- 16960772
TI  - Adenovirus transmission--worthy of our attention.

PMID- 16960773
TI  - Chemoprophylaxis of HIV infection: moving forward with caution.

PMID- 16960775
TI  - Human papillomavirus type 33 polymorphisms and high-grade squamous
      intraepithelial lesions of the uterine cervix.
AB  - BACKGROUND: We investigated the association between polymorphisms of human
      papillomavirus (HPV)-33 and squamous intraepithelial lesions (SILs). METHODS:
      Endocervical specimens from 89 women infected with HPV-33, out of a total of 5347
      recruited for 2 case-control and 2 cohort studies, were further analyzed by
      polymerase chain reaction sequencing of the long control region (LCR), E6, and
      E7. RESULTS: Of the 89 samples, 64 were normal, 7 had low-grade SILs (including 3
      determined by histopathologic analysis), 15 had high-grade SILs (HSILs, including
      14 determined by histopathologic analysis), and 3 had an unknown diagnosis. Non
      prototype-like LCR variants were significantly associated with HSILs (age- and
      study site-adjusted odds ratio [OR], 9.2 [95% confidence interval {CI}, 1.8
      45.9]). The C7732G variation, which results in the loss of a putative binding
      site for the cellular upstream stimulatory factor, was associated with HSILs (age
      and site-adjusted OR, 8.0 [95% CI, 1.5-42.8]). E6 and E7 polymorphisms were not
      associated with HSILs. Samples collected at 6-month intervals from 14
      participants contained the same variant. The HPV-33 MT 1-0-0 variant carrying the
      G7584A variation was detected more frequently in women from Brazil (7/20 [35%])
      than in women from Canada (1/65 [1.5%]; P=.001). CONCLUSION: Intratypic LCR
      variants of HPV-33 seem to vary geographically and to differ with respect to
      their oncogenic potential.

PMID- 16960774
TI  - Transmission dynamics and prospective environmental sampling of adenovirus in a
      military recruit setting.
AB  - BACKGROUND: High levels of morbidity caused by adenovirus among US military
      recruits have returned since the loss of adenovirus vaccines in 1999. The
      transmission dynamics of adenovirus have never been well understood, which
      complicates prevention efforts. METHODS: Enrollment and end-of-study samples were
      obtained and active surveillance for febrile respiratory illnesses (FRIs) was
      performed for 341 recruits and support personnel. Environmental samples were
      collected simultaneously. Classic and advanced diagnostic techniques were used.
      RESULTS: Seventy-nine percent (213/271) of new recruits were seronegative for
      either adenovirus serotype 4 (Ad-4) or adenovirus serotype 7 (Ad-7). FRI caused
      by Ad-4 was observed in 25% (67/271) of enrolled recruits, with 100% of them
      occurring in individuals with enrollment titers <1 : 4. The percentage of
      recruits seropositive for Ad-4 increased from 34% at enrollment to 97% by the end
      of the study. Adenovirus was most commonly detected in the environment on
      pillows, lockers, and rifles. CONCLUSIONS: Potential sources of adenovirus
      transmission among US military recruits included the presence of adenovirus on
      surfaces in living quarters and extended pharyngeal viral shedding over the
      course of several days. The introduction of new recruits, who were still shedding
      adenovirus, into new training groups was documented. Serological screening could
      identify susceptible recruits for the optimal use of available vaccines. New high
      throughput technologies show promise in providing valuable data for clinical and
      research applications.

PMID- 16960776
TI  - Interferon (IFN)-gamma-inducible protein-10: association with histological
      results, viral kinetics, and outcome during treatment with pegylated IFN-alpha 2a
      and ribavirin for chronic hepatitis C virus infection.
AB  - BACKGROUND: We investigated associations between interferon (IFN)-gamma-inducible
      protein (IP)-10 and liver histological results, viral kinetic response, and
      treatment outcome in patients infected with hepatitis C virus (HCV) genotypes 1
      4. METHODS: Plasma IP-10 was monitored before, during, and after treatment with
      pegylated IFN- alpha 2a and ribavirin in 265 HCV-infected patients. RESULTS: In
      univariate analyses, a low baseline IP-10 level was significantly associated with
      low baseline viral load, rapid viral response (RVR), a sustained viral response
      (SVR), body mass index <25 kg/m2, and less-pronounced fibrosis, inflammation, and
      steatosis (for HCV genotypes other than 3). When the results of the univariate
      analyses were included in multivariate analyses, a low plasma IP-10 level, low
      baseline viral load, and genotype 2 or 3 infection were independent predictors of
      an RVR and SVR. IP-10 levels decreased 6 weeks into treatment and remained low in
      patients with an SVR. By contrast, plasma levels of IP-10 rebounded in patients
      who had detectable HCV RNA after the completion of treatment. Using cutoff IP-10
      levels of 150 and 600 pg/mL for predicting an SVR in patients infected with HCV
      genotype 1 yielded a specificity and sensitivity of 81% and 95%, respectively.
      CONCLUSION: Baseline IP-10 levels are predictive of the response to HCV
      treatment.

PMID- 16960777
TI  - Chemoprophylaxis with tenofovir disoproxil fumarate provided partial protection
      against infection with simian human immunodeficiency virus in macaques given
      multiple virus challenges.
AB  - We examined the efficacy of tenofovir disoproxil fumarate (TDF) in blocking
      simian human immunodeficiency virus (SHIV) infection in Chinese rhesus macaques.
      Once weekly for 14 weeks or until a macaque became infected, 12 male macaques
      were inoculated intrarectally with amounts of SHIV(SF162P3) (10 median tissue
      culture infective doses; 3.8 x 10(5) virus particles) that were approximately 5
      fold higher than the human immunodeficiency virus type 1 RNA levels noted in
      human semen during an acute infection. Of the 12 macaques, 4 received oral TDF
      daily, 4 received oral TDF once weekly, and 4 (control animals) received no TDF.
      The control animals became infected after receiving a median of 1.5 virus
      inoculations; macaques receiving TDF daily (1 macaque remained uninfected after
      14 inoculations) and those receiving TDF weekly became infected after a median
      duration of 6.0 and 7.0 weeks, respectively. Although infection was delayed in
      treated macaques, compared with control macaques, the differences were not
      statistically significant (P=.315); however, the study was limited by the small
      numbers of animals evaluated and the variability in blood levels of TDF that
      resulted from oral dosing. These data demonstrate that treatment with oral TDF
      provided partial protection against SHIV infection but ultimately did not protect
      all TDF treated animals against multiple virus challenges.

PMID- 16960778
TI  - Repeated intravaginal inoculation with cell-associated simian immunodeficiency
      virus results in persistent infection of nonhuman primates.
AB  - The goal of the present study was to develop a nonhuman primate model of
      intravaginal human immunodeficiency virus (HIV) transmission with cell-associated
      virus. Reproductively mature, cycling cynomolgus macaques with or without
      chemically induced, transient ulcers of the lower female reproductive tract
      repeatedly received challenge with a variable amount of in vitro simian
      immunodeficiency virus mac239-infected peripheral blood mononuclear cells.
      Persistent viremia was established with surprisingly few infectious lymphocytes
      containing physiologically relevant quantities of cell-associated virus. This
      model will be indispensable for the testing of vaccines and topical agents that
      are aimed toward the prevention of heterosexual transmission of HIV.

PMID- 16960779
TI  - HIV-1 immune suppression and antimalarial treatment outcome in Zambian adults
      with uncomplicated malaria.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-1 infected adults with low CD4
      cell count have a higher risk of malaria infection and clinical malaria. We
      assessed the influence that HIV-1 immune suppression has on the efficacy of
      antimalarial treatment in adults with uncomplicated malaria. METHODS: This
      clinical trial included 971 Zambian adults with uncomplicated malaria. Patients
      were tested for HIV-1, and, if positive, a CD4 cell count was assessed. The
      primary outcome was recurrent parasitemia corrected by molecular genotyping
      within 45 days after treatment. RESULTS: HIV-1 infection was detected in 33%
      (320/971) of adult patients with malaria. Treatment failure was not associated
      with HIV-1 infection (relative risk [RR], 1.12 [95% confidence interval {CI},
      0.82-1.53]; P=.45). HIV-1-infected patients with a CD4 cell count <300
      cells/microL had an increased risk of recurrent parasitemia, compared with those
      with a CD4 cell count >or=300 cells/microL (RR, 2.24 [95% CI, 1.20-4.14]; P=.01).
      After genotyping, the risk of recrudescence was higher in HIV-1-infected patients
      with a CD4 cell count <300 cells/microL than in the other patients with malaria
      (RR, 1.67 [95% CI, 1.13-2.47]; P=.02). CONCLUSION: HIV-1-infected patients with
      malaria with a CD4 cell count <300 cells/microL have a higher risk of
      experiencing a recrudescent infection, compared with those with a CD4 cell count
      >or=300 cells/microL or without HIV-1 infection. Trial registered at
      http://www.clinicaltrials.gov/; reference number NCT00304980.

PMID- 16960780
TI  - Prevalence of CXCR4 tropism among antiretroviral-treated HIV-1-infected patients
      with detectable viremia.
AB  - Although CXCR4-tropic viruses are relatively uncommon among untreated human
      immunodeficiency virus (HIV)-infected individuals except during advanced
      immunodeficiency, the prevalence of CXCR4-tropic viruses among treated patients
      with detectable viremia is unknown. To address this issue, viral coreceptor usage
      was measured with a single-cycle recombinant-virus phenotypic entry assay in
      treatment-naive and treated HIV-infected participants with detectable viremia
      sampled from 2 clinic-based cohorts. Of 182 treated participants, 75 (41%)
      harbored dual/mixed or X4-tropic viruses, compared with 178 (18%) of the 976
      treatment-naive participants (P<.001). This difference remained significant after
      adjustment for CD4+ T cell count and CCR5 Delta 32 genotype. Enrichment for
      dual/mixed/X4-tropic viruses among treated participants was largely but
      incompletely explained by lower pretreatment nadir CD4 + T cell counts. CCR5
      inhibitors may thus be best strategically used before salvage therapy and before
      significant CD4 + T cell depletion.

PMID- 16960781
TI  - Longitudinal analysis of simian immunodeficiency virus (SIV) replication in the
      lungs: compartmentalized regulation of SIV.
AB  - BACKGROUND: Before the onset of AIDS, replication of human immunodeficiency virus
      (HIV) and simian immunodeficiency virus (SIV) in the lungs is considered to be
      latent. When and how virus replication is controlled in the lungs is unclear. In
      the present study, we examine virus replication in the lungs and in cells
      recovered from bronchoalveolar lavage (BAL) samples in a comprehensive,
      longitudinal analysis of an SIV/macaque model. METHODS: Gene-specific RNA and DNA
      were quantitated by polymerase chain reaction (PCR) and by real-time reverse
      transcription PCR (RT-PCR). Alveolar macrophages were isolated using Dynabeads
      CD14 (Invitrogen). Expression of CCAAT/enhancer-binding protein beta (C/EBP beta
      ) isoforms was examined by Western blot analysis. RESULTS: SIV replication
      occurred in the lungs during acute infection and correlated with plasma viral
      load. Innate immune responses involving interferon- beta and the dominant
      negative isoform of C/EBP beta were induced at this time. SIV RNA expression was
      suppressed in the lungs during asymptomatic infection, when no correlation
      existed with plasma viral load until SIV RNA levels rebounded again during late
      stage disease. Modulation of viral RNA levels in BAL cells reflected RNA levels
      in lung tissue throughout each phase of infection. CONCLUSION: Quantitation of
      SIV RNA in BAL cells provides a consistent surrogate assessment of virus
      replication in lung tissue. Innate immune responses contribute to
      compartmentalized suppression of acute SIV replication in the lungs.

PMID- 16960783
TI  - Promoter polymorphism of the anion-exchange protein 1 associated with severe
      malarial anemia and fatality.
AB  - The anion-exchange protein 1 (AE1 or band 3) is involved in the erythrocyte
      invasion of the malaria parasite Plasmodium falciparum, the adhesion of infected
      erythrocytes to endothelial cells, and the regulation of acid-base homeostasis,
      which is a critical factor for human survival in severe malaria. A variant of the
      AE1 gene promoter 512 base pairs (bp) distant from the transcription start site
      and 5699 bp from the translation start codon (AE1(-5699T-->C)) has been shown to
      be highly frequent in a population from the Ashanti region, Ghana. In a matched
      pair case-control study (736 pairs), children heterozygous for the mutation (AE1(
      5699CT)) had an increased risk of severe malarial anemia (odds ratio [OR], 1.45
      [95% confidence interval {CI}, 1.05-2.01]; P<.03). In children who developed this
      complication, carriers of the mutation AE1(-5699C) had a higher fatality rate
      than those with the genotype AE1(-5699TT) (relative risk, 7.1 [95% CI, 1.0
      52.8]). Moreover, in children with cerebral malaria, AE1(-5699C) was positively
      associated with a distinctive metabolic acidosis (P<.002), and results of
      luciferase assays showed higher transcriptional activity of the AE1(-5699C)
      allele. These results demonstrate that the AE1 promoter allele might influence
      the infection phenotype and the risk of fatal outcome in children with severe
      malaria. In this regard, a crucial role of the AE1 protein in malaria is
      emphasized.

PMID- 16960782
TI  - Physical linkage to drug resistance genes results in conservation of var genes
      among West Pacific Plasmodium falciparum isolates.
AB  - The multicopy var gene family encoding the variant surface antigen Plasmodium
      falciparum erythrocyte membrane protein 1 is highly diverse, with little overlap
      between different P. falciparum isolates. We report 5 var genes (varS1-varS5)
      that are shared at relatively high frequency among 63 genetically diverse P.
      falciparum isolates collected from 5 islands in the West Pacific region. The
      varS1, varS2, and varS3 genes were localized to the internal region on chromosome
      4, approximately 200 kb from pfdhfr-ts, whereas varS4 and varS5 were mapped to an
      internal region of chromosome 7, within 100 kb of pfcrt. The presence of varS2
      and varS3 were significantly correlated with the pyrimethamine-resistant pfdhfr
      genotype, whereas varS4 was strongly correlated with the chloroquine-resistant
      pfcrt genotype. Thus, the conservation of these var genes is the result of their
      physical linkage with drug-resistant genes in combination with the antimalarial
      drug pressure in the region.

PMID- 16960784
TI  - Interferon (IFN)-gamma , tumor necrosis factor-alpha , interleukin-6, and IFN
      gamma receptor 1 are the major immunological determinants associated with post
      kala azar dermal leishmaniasis.
AB  - Semiquantitative reverse-transcription polymerase chain reaction was used to
      analyze intralesional cytokine gene expression in 28 patients with post-kala azar
      dermal leishmaniasis (PKDL) and 14 patients with kala azar (KA). The data
      revealed mixed T helper cell type 1 (Th1) and T helper cell type 2 (Th2)
      responses, as reflected by elevated expression of interferon (IFN)-gamma , tumor
      necrosis factor (TNF)-alpha , transforming growth factor (TGF)-beta , interleukin
      (IL)-10, IL-6, and IL-4 mRNA, with minimal expression of IFN-gamma receptor 1
      (IFN-gamma R1) mRNA in PKDL lesions, compared with that in normal skin tissue. In
      comparison with those in KA lesions, mRNA levels for IFN-gamma , TNF-alpha , and
      IL-6 were found to be significantly elevated in PKDL lesions, implying that these
      cytokines play an important role in PKDL pathogenesis. In the presence of
      elevated levels of IFN-gamma and TNF-alpha , interference with type 1 effector
      activity in PKDL may be due to minimal expression of the IFN-gamma R1 gene or the
      simultaneous presence of elevated levels of IL-10, IL-6, and TGF-beta , which
      have counteracting effects. After treatment, the restoration of IFN-gamma R1 at
      both mRNA and protein levels, coupled with down-regulation of counteracting
      cytokines, may facilitate the action of signals associated with IFN-gamma ,
      yielding parasite clearance. Therefore, unfavorable clinical evolution in PKDL
      may not be due to the absence of an intralesional Th1 response but rather may be
      due to the presence of counteracting cytokines along with the down-modulation of
      IFN-gamma R1.

PMID- 16960785
TI  - Vaccination of dogs against Echinococcus granulosus, the cause of cystic hydatid
      disease in humans.
AB  - Dogs are pivotal in Echinococcus granulosus transmission to humans, and dog
      vaccination provides a very practical and cost-effective prevention strategy. We
      vaccinated dogs with soluble native proteins isolated from protoscoleces of E.
      granulosus and induced significant suppression of worm growth and egg production.
      Accordingly, we tested for vaccine efficacy using recombinant proteins derived
      from a developmentally regulated gene family (egM) specifically expressed in
      mature adult E. granulosus worms. Three egM genes--egM4, egM9, and egM123--were
      subcloned into an expression vector that expressed the molecules as soluble
      glutathione S-transferase (GST) fusion proteins in Escherichia coli. The 3 fusion
      proteins were purified for dog vaccination trials (3 doses of 80
      microg/protein/dog) in which the dogs were challenged and then necropsied 45 days
      after infection. Compared with worms in the control dogs that received GST, the 3
      recombinant proteins induced a very high level of protection (97%-100%) in terms
      of suppression of worm growth and, especially, of egg development and
      embryogenesis. We have thus shown that vaccination of the dog host against E.
      granulosus is feasible when recombinant proteins are used. Because the egg stage
      is crucial in the echinococcal life cycle, successful suppression of egg
      development by vaccination would halt transmission to intermediate hosts, thereby
      effecting long-term control.

PMID- 16960786
TI  - Modulation of the triggering receptor expressed on myeloid cells-1 pathway during
      pneumonia in rats.
AB  - BACKGROUND: Triggering receptor expressed on myeloid cells-1 (TREM-1) is a cell
      surface molecule that has been identified on both human and murine
      polymorphonuclear neutrophils and mature monocytes. The activation of TREM-1 in
      the presence of microbial components amplifies the inflammatory response and may
      be responsible for the hyperresponsiveness observed during the initial stage of
      sepsis. The aim of the present study was to investigate the effect of the
      modulation of the TREM-1 pathway during experimental pneumonia in rats. METHODS:
      Adult male Wistar rats were intratracheally inoculated with Pseudomonas
      aeruginosa (PAO1 strain) and randomly treated or not treated with an analogue
      synthetic peptide derived from the extracellular moiety of TREM-1 (LP17).
      RESULTS: P. aeruginosa induced a severe pneumonia associated with signs of severe
      sepsis within the first 24 h. In septic rats, LP17 improved hemodynamic status,
      attenuated the development of lactic acidosis and hypoxemia, modulated lung and
      systemic inflammatory responses and coagulation activation, reduced lung
      histological damage, and improved survival. CONCLUSIONS: The modulation of the
      TREM-1 pathway by the use of such synthetic peptides as LP17 appears beneficial
      during P. aeruginosa pneumonia in rats in attenuating lung and systemic
      inflammatory responses.

PMID- 16960787
TI  - Region of difference 1 antigen-specific CD4+ memory T cells correlate with a
      favorable outcome of tuberculosis.
AB  - BACKGROUND: Interferon (IFN)-gamma response to region of difference (RD) 1
      proteins (culture filtrate 10 and early secreted antigenic target 6) or
      overlapping peptides is a novel diagnostic marker of tuberculosis (TB) infection.
      Because we have recently shown that the response to certain peptides selected
      from RD1 allows discrimination between active TB (A-TB) and successfully treated
      TB (T-TB), we analyzed here the effector memory T cell profile and RD1-specific
      responses under the same clinical conditions. METHODS: T cell responses to RD1
      antigens were analyzed in patients with either severe or mild A-TB (classified on
      the basis of radiological lesions) and in 2 sets of healthy control subjects-
      those who had been successfully treated (the T-TB control subjects) and those
      whose tuberculin skin test (TST) results were negative (the TST-negative control
      subjects). IFN-gamma -producing CD4+ effector T cells were monitored by flow
      cytometric analysis and ex vivo enzyme-linked immunospot (ELISPOT) assay, whereas
      a "cultured" ELISPOT assay was used to determine the frequency of memory T cells.
      RESULTS: In the patients with severe A-TB, both CD4-mediated effector memory and
      central memory responses to the selected RD1 peptides were almost absent, whereas
      these responses were found in the majority of the patients with mild A-TB. In
      contrast, recognition of the selected RD1 peptides was detected in the T-TB
      control subjects only by expanding the central memory T cell pool. CONCLUSIONS:
      These data suggest a protective role for RD1 peptide-specific CD4+ effector T
      cells, which undergo clonal expansion during Mycobacterium tuberculosis
      replication and then a contraction phase after disease resolution, culminating in
      the generation of CD4+ memory T cells.

PMID- 16960788
TI  - Interleukin-18 protects splenectomized mice from lethal Streptococcus pneumoniae
      sepsis independent of interferon-gamma by inducing IgM production.
AB  - The mechanism of the susceptibility of splenectomized mice to Streptococcus
      pneumoniae infection and the therapeutic effect of interleukin (IL)-18 were
      investigated. We demonstrated that, although S. pneumoniae challenge induced IL
      12 production, it did not induce either interferon (IFN)-gamma or IL-18
      production in mice with or without a splenectomy. Liver mononuclear cells
      stimulated with heat-killed S. pneumoniae but not with viable S. pneumoniae
      produced IFN- gamma in vitro. However, IL-18 pretreatment recovered the low serum
      immunoglobulin (Ig) M levels in splenectomized mice and completely inhibited
      mortality after S. pneumoniae infection without any IFN-gamma up-regulation.
      Injection of IgM from noninfected control mice into splenectomized mice before
      infection confirmed the essential role that IgM plays against S. pneumoniae
      infection. Therefore, low serum IgM levels but not a low IFN-gamma response in
      splenectomized mice cause lethality in S. pneumoniae infection, and IL-18
      pretreatment protects them from infection by increasing IgM levels before
      infection.

PMID- 16960789
TI  - Chloroquine prevents T lymphocyte suppression induced by anthrax lethal toxin.
AB  - Lysosomal processing of lethal toxin (LTX) is a key event in the pathogenesis of
      anthrax. This study investigated the ability of chloroquine (CQ) to interfere
      with this processing and thereby to reduce suppression of T lymphocytes. T
      lymphocytes isolated from blood were activated, by cross-linking of CD3, in both
      the absence and presence of LTX and CQ and then were assayed by flow cytometry
      and immunoblotting. LTX was found to disrupt intracellular signaling, and it down
      regulated T lymphocyte function. CQ significantly reduced the harmful effects of
      LTX and protected the activation and cytokine production of T lymphocytes. This
      effect may indicate a promising strategy in the treatment of anthrax.

PMID- 16960791
TI  - Human herpesvirus 6 genome integration: a possible cause of misdiagnosis of
      active viral infection?

PMID- 16960790
TI  - Triazole-polyene antagonism in experimental invasive pulmonary aspergillosis: in
      vitro and in vivo correlation.
AB  - Combination antifungal therapy is increasingly used in the treatment of invasive
      aspergillosis. Whether the interaction between amphotericin B and triazoles is
      antagonistic against invasive aspergillosis is a controversial issue that is not
      likely to be resolved through a randomized clinical trial. Here, we found both in
      vitro and in vivo antagonism between liposomal amphotericin B and ravuconazole in
      simultaneous treatment of experimental invasive pulmonary aspergillosis in
      persistently neutropenic rabbits. Bliss independence-based drug-interaction
      modeling showed significant antagonism in vitro and in vivo, with the observed
      drug effects being 20%-69% lower than would be expected if the drugs were acting
      independently. These in vitro and in vivo findings of antagonism were consistent
      with the findings from Loewe additivity-based drug-interaction modeling. No
      pharmacokinetic interaction was found. The combination of a triazole and polyene
      may be antagonistic in the treatment of invasive pulmonary aspergillosis.

PMID- 16960792
TI  - Human herpesvirus 6 latency characterized by high viral load: chromosomal
      integration in many, but not all, cells.

PMID- 16960796
TI  - Origins of the human genome project: why sequence the human genome when 96% of it
      is junk?

PMID- 16960794
TI  - Paleoparasite populations from archived sera: insights into chloroquine drug
      resistance in Papua New Guinea.

PMID- 16960797
TI  - Reduction of sample heterogeneity through use of population substructure: an
      example from a population of African American families with sarcoidosis.
AB  - Sarcoidosis is a granulomatous inflammatory disorder of complex etiology with
      significant linkage to chromosome 5, and marginal linkage was observed to five
      other chromosomes in African Americans (AAs) in our previously published genome
      scan. Because genetic factors underlying complex disease are often population
      specific, genetic analysis of samples with diverse ancestry (i.e., ethnic
      confounding) can lead to loss of power. Ethnic confounding is often addressed by
      stratifying on self-reported race, a controversial and less-than-perfect
      construct. Here, we propose linkage analysis stratified by genetically determined
      ancestry as an alternative approach for reducing ethnic confounding. Using data
      from the 380 microsatellite markers genotyped in the aforementioned genome scan,
      we clustered AA families into subpopulations on the basis of ancestry similarity.
      Evidence of two genetically distinct groups was found: subpopulation one (S1)
      comprised 219 of the 229 families, subpopulation two (S2) consisted of six
      families (the remaining four families were a mixture). Stratified linkage results
      suggest that only the S1 families contributed to previously identified linkage
      signals at 1p22, 3p21-14, 11p15, and 17q21 and that only the S2 families
      contributed to those found at 5p15-13 and 20q13. Signals on 2p25, 5q11, 5q35, and
      9q34 remained significant in both subpopulations, and evidence of a new
      susceptibility locus at 2q37 was found in S2. These results demonstrate the
      usefulness of stratifying on genetically determined ancestry, to create
      genetically homogeneous subsets--more reliable and less controversial than race
      stratified subsets--in which to identify genetic factors. Our findings support
      the presence of sarcoidosis-susceptibility genes in regions identified elsewhere
      but indicate that these genes are likely to be ancestry specific.

PMID- 16960798
TI  - Genetic mapping at 3-kilobase resolution reveals inositol 1,4,5-triphosphate
      receptor 3 as a risk factor for type 1 diabetes in Sweden.
AB  - We mapped the genetic influences for type 1 diabetes (T1D), using 2,360 single
      nucleotide polymorphism (SNP) markers in the 4.4-Mb human major
      histocompatibility complex (MHC) locus and the adjacent 493 kb centromeric to the
      MHC, initially in a survey of 363 Swedish T1D cases and controls. We confirmed
      prior studies showing association with T1D in the MHC, most significantly near
      HLA-DR/DQ. In the region centromeric to the MHC, we identified a peak of
      association within the inositol 1,4,5-triphosphate receptor 3 gene (ITPR3;
      formerly IP3R3). The most significant single SNP in this region was at the center
      of the ITPR3 peak of association (P=1.7 x 10(-4) for the survey study). For
      validation, we typed an additional 761 Swedish individuals. The P value for
      association computed from all 1,124 individuals was 1.30 x 10(-6) (recessive odds
      ratio 2.5; 95% confidence interval [CI] 1.7-3.9). The estimated population
      attributable risk of 21.6% (95% CI 10.0%-31.0%) suggests that variation within
      ITPR3 reflects an important contribution to T1D in Sweden. Two-locus regression
      analysis supports an influence of ITPR3 variation on T1D that is distinct from
      that of any MHC class II gene.

PMID- 16960799
TI  - A new method for detecting human recombination hotspots and its applications to
      the HapMap ENCODE data.
AB  - Computational detection of recombination hotspots from population polymorphism
      data is important both for understanding the nature of recombination and for
      applications such as association studies. We propose a new method for this task
      based on a multiple-hotspot model and an (approximate) log-likelihood ratio test.
      A truncated, weighted pairwise log-likelihood is introduced and applied to the
      calculation of the log-likelihood ratio, and a forward-selection procedure is
      adopted to search for the optimal hotspot predictions. The method shows a
      relatively high power with a low false-positive rate in detecting multiple
      hotspots in simulation data and has a performance comparable to the best results
      of leading computational methods in experimental data for which recombination
      hotspots have been characterized by sperm-typing experiments. The method can be
      applied to both phased and unphased data directly, with a very fast computational
      speed. We applied the method to the 10 500-kb regions of the HapMap ENCODE data
      and found 172 hotspots among the three populations, with average hotspot width of
      2.4 kb. By comparisons with the simulation data, we found some evidence that
      hotspots are not all identical across populations. The correlations between
      detected hotspots and several genomic characteristics were examined. In
      particular, we observed that DNaseI-hypersensitive sites are enriched in
      hotspots, suggesting the existence of human beta hotspots similar to those found
      in yeast.

PMID- 16960800
TI  - A genomewide single-nucleotide-polymorphism panel with high ancestry information
      for African American admixture mapping.
AB  - Admixture mapping requires a genomewide panel of relatively evenly spaced markers
      that can distinguish the ancestral origins of chromosomal segments in admixed
      individuals. Through use of the results of the International HapMap Project and
      specific selection criteria, the current study has examined the ability of
      selected single-nucleotide polymorphisms (SNPs) to extract continental ancestry
      information in African American subjects and to explore parameters for admixture
      mapping. Genotyping of two linguistically diverse West African populations (Bini
      and Kanuri Nigerians, who are Niger-Congo [Bantu] and Nilo-Saharan speakers,
      respectively), European Americans, and African Americans validated a genomewide
      set of >4,000 SNP ancestry-informative markers with mean and median F(ST) values
      >0.59 and mean and median Fisher's information content >2.5. This set of SNPs
      extracted a larger amount of ancestry information in African Americans than
      previously reported SNP panels and provides nearly uniform coverage of the
      genome. Moreover, in the current study, simulations show that this more
      informative panel improves power for admixture mapping in African Americans when
      ethnicity risk ratios are modest. This is particularly important in the
      application of admixture mapping in complex genetic diseases for which only
      modest ethnicity risk ratios of relevant susceptibility genes are expected.

PMID- 16960801
TI  - Mutations in SLC34A2 cause pulmonary alveolar microlithiasis and are possibly
      associated with testicular microlithiasis.
AB  - Pulmonary alveolar microlithiasis (PAM) is a rare disease characterized by the
      deposition of calcium phosphate microliths throughout the lungs. We first
      identified a PAM locus by homozygosity mapping to 4p15, then identified, by a
      candidate-gene approach, the gene responsible for the disease as SLC34A2 (the
      type IIb sodium-phosphate cotransporter gene), which is involved in phosphate
      homeostasis in several organs. We identified six homozygous exonic mutations in
      the seven unrelated patients with PAM we studied. Three of the mutations were
      frameshifts, one was a chain termination, one was an amino acid substitution, and
      one was a deletion spanning the minimal promoter and the first exon. Absence of
      functional protein product of the gene is compatible with calcium phosphate
      deposition in alveolar airspaces. We show that impaired activity of the phosphate
      transporter is presumably responsible for the microliths and that PAM is a
      recessive monogenic disease with full penetrance. Testicular microlithiasis (TM)
      is a disease that is more common than PAM. It is often associated with cancer and
      infertility. Since the gene we identified is also expressed in testis, we
      searched for mutations in subjects with TM. In 2 of the 15 subjects with TM we
      studied, we identified two rare variants, one synonymous and the other noncoding,
      that are possibly associated with the condition.

PMID- 16960802
TI  - Mutations in CABP4, the gene encoding the Ca2+-binding protein 4, cause autosomal
      recessive night blindness.
AB  - Mutations in genes encoding either components of the phototransduction cascade or
      proteins presumably involved in signaling from photoreceptors to adjacent second
      order neurons have been shown to cause congenital stationary night blindness
      (CSNB). Sequence alterations in CACNA1F lead to the incomplete type of CSNB
      (CSNB2), which can be distinguished by standard electroretinography (ERG). CSNB2
      is associated with a reduced rod b-wave, a substantially reduced cone a-wave, and
      a reduced 30-Hz flicker ERG response. CACNA1F encodes the alpha 1-subunit of an L
      type Ca2+ channel (Cav1.4 alpha ), which is specific to photoreceptors and is
      present at high density in the synaptic terminals. Ten of our patients with CSNB2
      showed no mutation in CACNA1F. To identify the disease-causing mutations, we used
      a candidate-gene approach. CABP4, a member of the calcium-binding protein (CABP)
      family, is located in photoreceptor synaptic terminals and is directly associated
      with the C-terminal domain of the Cav1.4 alpha . Mice lacking either Cabp4 or
      Cav1.4 alpha display a CSNB2-like phenotype. Here, we report for the first time
      that mutations in CABP4 lead to autosomal recessive CSNB. Our studies revealed
      homozygous and compound heterozygous mutations in two families. We also show that
      these mutations reduce the transcript levels to 30%-40% of those in controls.
      This suggests that the reduced amount of CABP4 is the reason for the signaling
      defect in these patients.

PMID- 16960803
TI  - Satb2 haploinsufficiency phenocopies 2q32-q33 deletions, whereas loss suggests a
      fundamental role in the coordination of jaw development.
AB  - The recent identification of SATB2 as a candidate gene responsible for the
      craniofacial dysmorphologies associated with deletions and translocations at 2q32
      q33, one of only three regions of the genome for which haploinsufficiency has
      been significantly associated with isolated cleft palate, led us to investigate
      the in vivo functions of murine Satb2. We find that, similar to the way in which
      SATB2 is perceived to act in humans, craniofacial defects due to
      haploinsufficiency of Satb2, including cleft palate (in approximately 25% of
      cases), phenocopy those seen with 2q32-q33 deletions and translocations in
      humans. Full functional loss of Satb2 results in amplification of these defects
      and leads both to increased apoptosis in the craniofacial mesenchyme where Satb2
      is usually expressed and to changes in the pattern of expression of three genes
      implicated in the regulation of craniofacial development in humans and mice:
      Pax9, Alx4, and Msx1. The Satb2-dosage sensitivity in craniofacial development is
      conspicuous--along with its control of cell survival, pattern of expression, and
      reversible functional modification by SUMOylation, it suggests that Satb2/SATB2
      function in craniofacial development may prove to be more profound than has been
      anticipated previously. Because jaw development is Satb2-dosage sensitive, the
      regulators of Satb2 expression and posttranslational modification become of
      critical importance both ontogenetically and evolutionarily, especially since
      such regulators plausibly play undetected roles in jaw and palate development and
      in the etiology of craniofacial malformations.

PMID- 16960804
TI  - A flexible Bayesian framework for modeling haplotype association with disease,
      allowing for dominance effects of the underlying causative variants.
AB  - Multilocus analysis of single-nucleotide-polymorphism (SNP) haplotypes may
      provide evidence of association with disease, even when the individual loci
      themselves do not. Haplotype-based methods are expected to outperform single-SNP
      analyses because (i) common genetic variation can be structured into haplotypes
      within blocks of strong linkage disequilibrium and (ii) the functional properties
      of a protein are determined by the linear sequence of amino acids corresponding
      to DNA variation on a haplotype. Here, I propose a flexible Bayesian framework
      for modeling haplotype association with disease in population-based studies of
      candidate genes or small candidate regions. I employ a Bayesian partition model
      to describe the correlation between marker-SNP haplotypes and causal variants at
      the underlying functional polymorphism(s). Under this model, haplotypes are
      clustered according to their similarity, in terms of marker-SNP allele matches,
      which is used as a proxy for recent shared ancestry. Haplotypes within a cluster
      are then assigned the same probability of carrying a causal variant at the
      functional polymorphism(s). In this way, I can account for the dominance effect
      of causal variants, here corresponding to any deviation from a multiplicative
      contribution to disease risk. The results of a detailed simulation study
      demonstrate that there is minimal cost associated with modeling these dominance
      effects, with substantial gains in power over haplotype-based methods that do not
      incorporate clustering and that assume a multiplicative model of disease risks.

PMID- 16960805
TI  - Genomewide linkage screen for Waldenstrom macroglobulinemia susceptibility loci
      in high-risk families.
AB  - Waldenstrom macroglobulinemia (WM), a distinctive subtype of non-Hodgkin lymphoma
      that features overproduction of immunoglobulin M (IgM), clearly has a familial
      component; however, no susceptibility genes have yet been identified. We
      performed a genomewide linkage analysis in 11 high-risk families with WM that
      were informative for linkage, for a total of 122 individuals with DNA samples,
      including 34 patients with WM and 10 patients with IgM monoclonal gammopathy of
      undetermined significance (IgM MGUS). We genotyped 1,058 microsatellite markers
      (average spacing 3.5 cM), performed both nonparametric and parametric linkage
      analysis, and computed both two-point and multipoint linkage statistics. The
      strongest evidence of linkage was found on chromosomes 1q and 4q when patients
      with WM and with IgM MGUS were both considered affected; nonparametric linkage
      scores were 2.5 (P=.0089) and 3.1 (P=.004), respectively. Other locations
      suggestive of linkage were found on chromosomes 3 and 6. Results of two-locus
      linkage analysis were consistent with independent effects. The findings from this
      first linkage analysis of families at high risk for WM represent important
      progress toward identifying gene(s) that modulate susceptibility to WM and toward
      understanding its complex etiology.

PMID- 16960806
TI  - CRYBA4, a novel human cataract gene, is also involved in microphthalmia.
AB  - Genetic analysis of a large Indian family with an autosomal dominant cataract
      phenotype allowed us to identify a novel cataract gene, CRYBA4. After a
      genomewide screen, linkage analysis identified a maximum LOD score of 3.20
      (recombination fraction [theta] 0.001) with marker D22S1167 of the beta 
      crystallin gene cluster on chromosome 22. To date, CRYBA4 was the only gene in
      this cluster not associated with either human or murine cataracts. A pathogenic
      mutation was identified in exon 4 that segregated with the disease status. The
      c.317T-->C sequence change is predicted to replace the highly conserved
      hydrophobic amino acid phenylalanine94 with the hydrophilic amino acid serine.
      Modeling suggests that this substitution would significantly reduce the intrinsic
      stability of the crystalline monomer, which would impair its ability to form the
      association modes critical for lens transparency. Considering that CRYBA4
      associates with CRYBB2 and that the latter protein has been implicated in
      microphthalmia, mutational analysis of CRYBA4 was performed in 32 patients
      affected with microphthalmia (small eye). We identified a c.242T-->C (Leu69Pro)
      sequence change in exon 4 in one patient, which is predicted here to disrupt the
      beta -sheet structure in CRYBA4. Protein folding would consequently be impaired,
      most probably leading to a structure with reduced stability in the mutant. This
      is the first report linking mutations in CRYBA4 to cataractogenesis and
      microphthalmia.

PMID- 16960808
TI  - Linkage analysis identifies a novel locus for restless legs syndrome on
      chromosome 2q in a South Tyrolean population isolate.
AB  - Restless legs syndrome (RLS) is a common neurological condition with three loci
      (12q, 14q, and 9p) described so far, although none of these genes has yet been
      identified. We report a genomewide linkage scan of patients with RLS (n=37)
      assessed in a population isolate (n=530) of South Tyrol (Italy). Using both
      nonparametric and parametric analyses, we initially obtained suggestive evidence
      of a novel locus on chromosome 2q, with nominal evidence of linkage on
      chromosomes 5p and 17p. Follow-up genotyping yielded significant evidence of
      linkage (nonparametric LOD score 5.5, P<or=.0000033; heterogeneity LOD score 5.1;
      alpha =1.0) on chromosome 2q. Three families (S01, S05, and S016) were shown to
      descend from a common founder couple. A disease haplotype shared between family
      S01 and family S05 defines a candidate region of 8.2 cM; in addition, the single
      affected individual in family S016 shares three linked alleles at neighboring
      markers, which suggests a reduced candidate interval of only 1.6 cM. Two-point
      linkage analysis in this 10-generation pedigree provided significant evidence of
      a novel RLS locus in this region (LOD score 4.1). These findings reemphasize the
      genetic heterogeneity of the disorder and strongly support the identification of
      a novel locus for RLS on chromosome 2q.

PMID- 16960807
TI  - HLA-B maternal-fetal genotype matching increases risk of schizophrenia.
AB  - Schizophrenia and human leukocyte antigen (HLA) matching between couples or
      between mothers and offspring have independently been associated with
      prenatal/obstetric complications, including preeclampsia and low birth weight.
      Here, we report the results of a family-based candidate-gene study that brings
      together these two disparate lines of research by assessing maternal-fetal
      genotype matching at HLA-A, -B, and -DRB1 as a risk factor of schizophrenia. We
      used a conditional-likelihood modeling approach with a sample of 274 families
      that had at least one offspring with schizophrenia or a related spectrum
      disorder. A statistically significant HLA-B maternal-fetal genotype-matching
      effect on schizophrenia was demonstrated for female offspring (P=.01; parameter
      estimate 1.7 [95% confidence interval 1.22-2.49]). Because the matching effect
      could be associated with pregnancy complications rather than with schizophrenia
      per se, these findings are consistent with the neurodevelopmental hypothesis of
      schizophrenia and with accumulating evidence that the prenatal period is involved
      in the origins of this disease. Our approach demonstrates how genetic markers can
      be used to characterize the biology of prenatal risk factors of schizophrenia.

PMID- 16960809
TI  - Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa
      reticularis: two allelic ectodermal dysplasias caused by dominant mutations in
      KRT14.
AB  - Naegeli-Franceschetti-Jadassohn syndrome (NFJS) and dermatopathia pigmentosa
      reticularis (DPR) are two closely related autosomal dominant ectodermal dysplasia
      syndromes that clinically share complete absence of dermatoglyphics (fingerprint
      lines), a reticulate pattern of skin hyperpigmentation, thickening of the palms
      and soles (palmoplantar keratoderma), abnormal sweating, and other subtle
      developmental anomalies of the teeth, hair, and skin. To decipher the molecular
      basis of these disorders, we studied one family with DPR and four families with
      NFJS. We initially reassessed linkage of NFJS/DPR to a previously established
      locus on 17q11.2-q21. Combined multipoint analysis generated a maximal LOD score
      of 8.3 at marker D17S800 at a recombination fraction of 0. The disease interval
      was found to harbor 230 genes, including a large cluster of keratin genes.
      Heterozygous nonsense or frameshift mutations in KRT14 were found to segregate
      with the disease trait in all five families. In contrast with KRT14 mutations
      affecting the central alpha -helical rod domain of keratin 14, which are known to
      cause epidermolysis bullosa simplex, NFJS/DPR-associated mutations were found in
      a region of the gene encoding the nonhelical head (E1/V1) domain and are
      predicted to result in very early termination of translation. These data suggest
      that KRT14 plays an important role during ontogenesis of dermatoglyphics and
      sweat glands. Among other functions, the N-terminal part of keratin molecules has
      been shown to confer protection against proapoptotic signals. Ultrastructural
      examination of patient skin biopsy specimens provided evidence for increased
      apoptotic activity in the basal cell layer where KRT14 is expressed, suggesting
      that apoptosis is an important mechanism in the pathogenesis of NFJS/DPR.

PMID- 16960810
TI  - Familial chilblain lupus, a monogenic form of cutaneous lupus erythematosus, maps
      to chromosome 3p.
AB  - Systemic lupus erythematosus is a prototypic autoimmune disease. Apart from rare
      monogenic deficiencies of complement factors, where lupuslike disease may occur
      in association with other autoimmune diseases or high susceptibility to bacterial
      infections, its etiology is multifactorial in nature. Cutaneous findings are a
      hallmark of the disease and manifest either alone or in association with internal
      organ disease. We describe a novel genodermatosis characterized by painful bluish
      red inflammatory papular or nodular lesions in acral locations such as fingers,
      toes, nose, cheeks, and ears. The lesions sometimes appear plaquelike and tend to
      ulcerate. Manifestation usually begins in early childhood and is precipitated by
      cold and wet exposure. Apart from arthralgias, there is no evidence for internal
      organ disease or an increased susceptibility to infection. Histological findings
      include a deep inflammatory infiltrate with perivascular distribution and
      granular deposits of immunoglobulins and complement along the basement membrane.
      Some affected individuals show antinuclear antibodies or immune complex
      formation, whereas cryoglobulins or cold agglutinins are absent. Thus, the
      findings are consistent with chilblain lupus, a rare form of cutaneous lupus
      erythematosus. Investigation of a large German kindred with 18 affected members
      suggests a highly penetrant trait with autosomal dominant inheritance. By single
      nucleotide-polymorphism-based genomewide linkage analysis, the locus was mapped
      to chromosome 3p. Haplotype analysis defined the locus to a 13.8-cM interval with
      a LOD score of 5.04. This is the first description of a monogenic form of
      cutaneous lupus erythematosus. Identification of the gene responsible for
      familial chilblain lupus may shed light on the pathogenesis of common forms of
      connective-tissue disease such as systemic lupus erythematosus.

PMID- 16960811
TI  - Identification of the gene encoding the enzyme deficient in mucopolysaccharidosis
      IIIC (Sanfilippo disease type C).
AB  - Mucopolysaccharidosis IIIC (MPS IIIC), or Sanfilippo C, represents the only MPS
      disorder in which the responsible gene has not been identified; however, the gene
      has been localized to the pericentromeric region of chromosome 8. In an ongoing
      proteomics study of mouse lysosomal membrane proteins, we identified an unknown
      protein whose human homolog, TMEM76, was encoded by a gene that maps to 8p11.1. A
      full-length mouse expressed sequence tag was expressed in human MPS IIIC
      fibroblasts, and its protein product localized to the lysosome and corrected the
      enzymatic defect. The mouse sequence was used to identify the full-length human
      homolog (HGSNAT), which encodes a protein with no homology to other proteins of
      known function but is highly conserved among plants and bacteria. Mutational
      analyses of two MPS IIIC cell lines identified a splice-junction mutation that
      accounted for three mutant alleles, and a single base-pair insertion accounted
      for the fourth.

PMID- 16960812
TI  - A genomewide search finds major susceptibility loci for nicotine dependence on
      chromosome 10 in African Americans.
AB  - Epidemiological studies have demonstrated that genetic factors account for at
      least 50% of the liability for nicotine dependence (ND). Although several linkage
      studies have been conducted, all samples to date were primarily of European
      origin. In this study, we conducted a genomewide scan of 1,261 individuals,
      representing 402 nuclear families, of African American (AA) origin. We examined
      385 autosomal microsatellite markers for ND, which was assessed by smoking
      quantity (SQ), the Heaviness of Smoking Index (HSI), and the Fagerstrom Test for
      ND (FTND). After performing linkage analyses using various methods implemented in
      the GENEHUNTER and S.A.G.E. programs, we found a region near marker D10S1432 on
      chromosome 10q22 that showed a significant linkage to indexed SQ, with a maximum
      LOD score of 4.17 at 92 cM and suggestive linkage to HSI, SQ, and log-transformed
      SQ. Additionally, we identified three regions that met the criteria for
      suggestive linkage to at least one ND measure: on chromosomes 9q31 at marker
      D9S1825, 11p11 between markers D11S1993 and D11S1344, and 13q13 between markers
      D13S325 and D13S788. Other locations on chromosomes 15p11, 17q25, and 18q12
      exhibited some evidence of linkage for ND (LOD >1.44). The four regions with
      significant or suggestive linkage were positive for multiple ND measures by
      multiple statistical methods. Some of these regions have been linked to smoking
      behavior at nominally significant levels in other studies, which provides
      independent replication of the regions for ND in different cohorts. In summary,
      we found significant linkage on chromosome 10q22 and suggestive linkage on
      chromosomes 9, 11, and 13 for major genetic determinants of ND in an AA sample.
      Further analysis of these positive regions by fine mapping and/or association
      analysis is thus warranted. To our knowledge, this study represents the first
      genomewide linkage scan of ND in an AA sample.

PMID- 16960813
TI  - LRRK2 G2019S in families with Parkinson disease who originated from Europe and
      the Middle East: evidence of two distinct founding events beginning two millennia
      ago.
AB  - The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is the most common
      genetic determinant of Parkinson disease (PD) identified to date. It accounts for
      1%-7% of PD in patients of European origin and 20%-40% in Ashkenazi Jews and
      North African Arabs with PD. Previous studies concluded that patients from these
      populations all shared a common Middle Eastern founder who lived in the 13th
      century. We tested this hypothesis by genotyping 25 microsatellite and single
      nucleotide-polymorphism markers in 22 families with G2019S and observed two
      distinct haplotypes. Haplotype 1 was present in 19 families of Ashkenazi Jewish
      and European ancestry, whereas haplotype 2 occurred in three European American
      families. Using a maximum-likelihood method, we estimated that the families with
      haplotype 1 shared a common ancestor 2,250 (95% confidence interval 1,650-3,120)
      years ago, whereas those with haplotype 2 appeared to share a more recent
      founder. Our data suggest two separate founding events for G2019S in these
      populations, beginning at a time that coincides with the Jewish Diasporas.

PMID- 16960814
TI  - A deleterious mutation in SAMD9 causes normophosphatemic familial tumoral
      calcinosis.
AB  - Familial tumoral calcinosis (FTC) is a rare autosomal recessive disorder
      characterized by the progressive deposition of calcified masses in cutaneous and
      subcutaneous tissues, which results in painful ulcerative lesions and severe skin
      and bone infections. Two major types of FTC have been recognized:
      hyperphosphatemic FTC (HFTC) and normophosphatemic FTC (NFTC). HFTC was recently
      shown to result from mutations in two different genes: GALNT3, which codes for a
      glycosyltransferase, and FGF23, which codes for a potent phosphaturic protein. To
      determine the molecular cause of NFTC, we performed homozygosity mapping in five
      affected families of Jewish Yemenite origin and mapped NFTC to 7q21-7q21.3.
      Mutation analysis revealed a homozygous mutation in the SAMD9 gene (K1495E),
      which was found to segregate with the disease in all families and to interfere
      with the protein expression. Our data suggest that SAMD9 is involved in the
      regulation of extraosseous calcification, a process of considerable importance in
      a wide range of diseases as common as atherosclerosis and autoimmune disorders.

PMID- 16960815
TI  - Parent-of-origin effect and risk for attention-deficit/hyperactivity disorder:
      balancing the evidence against bias and chance findings.

PMID- 16960817
TI  - Colorectal cancer risk in monoallelic carriers of MYH variants.

PMID- 16960819
TI  - Calix[6]arene-based template for X-ray crystallographic analysis of template
      assembled synthetic proteins.

PMID- 16960820
TI  - Henri Moissan: winner of the Nobel Prize for Chemistry 1906.

PMID- 16960821
TI  - A family of nanoporous materials based on an amino acid backbone.

PMID- 16960822
TI  - Formulation considerations for proteins susceptible to asparagine deamidation and
      aspartate isomerization.
AB  - The asparagine (Asn) deamidation and aspartate (Asp) isomerization reactions are
      nonenzymatic intra-molecular reactions occurring in peptides and proteins that
      are a source of major stability concern in the formulation of these biomolecules.
      The mechanisms for the deamidation and isomerization reactions are similar since
      they both proceed through an intra-molecular cyclic imide (Asu) intermediate. The
      formation of the Asu intermediate, which involves the attack by nitrogen of the
      peptide backbone on the carbonyl carbon of the Asn or the Asp side chain, is the
      rate-limiting step in both the deamidation and the isomerization reactions at
      physiological pH. In this article, the influence of factors such as formulation
      conditions, protein primary sequence, and protein structure on the reactivity of
      Asn and Asp residues in proteins are reviewed. The importance of formulation
      conditions such as pH and solvent dielectric in influencing deamidation and
      isomerization reaction rates is addressed. Formulation strategies that could
      improve the stability of proteins to deamidation and isomerization reactions are
      described. The review is intended to provide information to formulation
      scientists, based on protein sequence and structure, to predict potential
      degradative sites on a protein molecule and to enable formulation scientists to
      set appropriate formulation conditions to minimize reactivity of Asn and Asp
      residues in protein therapeutics.

PMID- 16960823
TI  - Nuclear magnetic resonance imaging of freeze-drying.
AB  - The objective of this study was to determine the feasibility of using magnetic
      resonance imaging (MRI) to observe the shape and position of the ice sublimation
      front during primary drying for subsequent comparison of these images with those
      predicted by mathematical model of heat and mass transfer during primary drying.
      One-dimensional (1D) profile studies on both ice and 2% HSA during in situ freeze
      drying were performed with a single point imaging (SPI) sequence, and
      demonstrated that the SPI technique can be used in capturing the ice signal
      during freeze-drying. In order to perform two-dimensional imaging, it was found
      that the ice must be "doped" in order to increase the apparent transverse
      relaxation time (T2*) and decrease the longitudinal relaxation time (T1) of ice.
      HBr at a level of 0.1 mM was shown to be an effective dopant. As a result, 2D
      images of ice and 5% HSA doped with 0.1 mM HBr were successfully collected, and
      the shape and position of the ice sublimation front during in situ freeze-drying
      were observed.

PMID- 16960824
TI  - Novel biopolymers as implant matrix for the delivery of ciprofloxacin:
      biocompatibility, degradation, and in vitro antibiotic release.
AB  - The purpose of this study was to investigate the in vitro-in vivo degradation and
      tissue compatibility of three novel biopolymers viz. polymerized rosin (PR),
      glycerol ester of polymerized rosin (GPR) and pentaerythritol ester of
      polymerized rosin (PPR) and study their potential as implant matrix for the
      delivery of ciprofloxacin hydrochloride. Free films of polymers were used for in
      vitro degradation in PBS (pH 7.4) and in vivo in rat subcutaneous model. Sample
      weight loss, molecular weight decline, and morphological changes were analyzed
      after periodic intervals (30, 60, and 90 days) to monitor the degradation
      profile. Biocompatibility was evaluated by examination of the inflammatory tissue
      response to the implanted films on postoperative days 7, 14, 21, and 28.
      Furthermore, direct compression of dry blends of various polymer matrices with
      20%, 30%, and 40% w/w drug loading was performed to investigate their potential
      for implant systems. The implants were characterized in terms of porosity and
      ciprofloxacin release. Biopolymer films showed slow rate of degradation, in vivo
      rate being faster on comparative basis. Heterogeneous bulk degradation was
      evident with the esterified products showing faster rates than PR.
      Morphologically all the films were stiff and intact with no significant
      difference in their appearance. The percent weight remaining in vivo was 90.70 +/
      6.2, 85.59 +/- 5.8, and 75.56 +/- 4.8 for PR, GPR, and PPR films respectively.
      Initial rapid drop in Mw was demonstrated with nearly 20.0% and 30.0% decline
      within 30 days followed by a steady decline to nearly 40.0% and 50.0% within 90
      days following in vitro and in vivo degradation respectively. Biocompatibility
      demonstrated by acute and subacute tissue reactions showed minimal inflammatory
      reactions with prominent fibrous encapsulation and absence of necrosis
      demonstrating good tissue compatibility to the extent evaluated. All implants
      showed erosion and increase in porosity that affected the drug release. Increase
      in drug loading significantly altered the ciprofloxacin release in extended
      dissolution studies. PPR produced drug release >90% over a period of 90 days
      promising its utility in implant systems. The results demonstrated the utility of
      novel film forming biopolymers as implant matrix for controlled/sustained drug
      delivery with excellent biocompatibility characteristics.

PMID- 16960825
TI  - A new tetrahydrated form of sodium naproxen.
AB  - The anhydrous sodium naproxen (ASN) can form several hydrated phases if
      maintained at different relative humidities (RH). The water uptake can promote
      crystallographic modifications, according to the amount of water. In a previous
      work, the authors showed that a dihydrated form could be obtained either by
      crystallization in water or by exposure of the anhydrous form to a RH of 55%. In
      the present work, the authors report about the formation and characterization of
      a new tetrahydrated form, obtained by exposing the ASN to RH >or= 75%. All the
      hydrated compounds were characterized by the combined use of several
      spectroscopic, thermal, and crystallographic techniques. The thermal stability of
      both the dihydrated and tetrahydrated compounds was also tested.

PMID- 16960826
TI  - Elastic liposomes mediated transdermal delivery of an anti-hypertensive agent:
      propranolol hydrochloride.
AB  - One major problem encountered in transdermal drug delivery is the low
      permeability of drugs through the skin barrier. In the present investigation
      ultradeformable lipid vesicles, that is, elastic liposomes were prepared
      incorporating propranolol hydrochloride for enhanced transdermal delivery.
      Elastic liposomes bearing propranolol hydrochloride were prepared by conventional
      rotary evaporation method and characterized for various parameters including
      vesicles shape and surface morphology, size and size distribution, entrapment
      efficiency, elasticity, turbidity, and in vitro drug release. In vitro flux,
      enhancement ratio (ER), and release pattern of propranolol hydrochloride were
      calculated for transdermal delivery. In vivo study conducted on male albino rats
      (Sprague Dawley) was also taken as a measure of performance of elastic liposomal,
      liposomal, and plain drug solution. The better permeation through the skin was
      confirmed by confocal laser scanning microscopy (CLSM). Results indicate that the
      elastic liposomal formulation for transdermal delivery of propranolol
      hydrochloride provides better transdermal flux, higher entrapment efficiency,
      ability as a self-penetration enhancer and effectiveness for transdermal delivery
      as compared to liposomes.

PMID- 16960827
TI  - Biodegradable polyurethane cancellous bone graft substitutes in the treatment of
      iliac crest defects.
AB  - Porous scaffolds were produced from newly designed biodegradable, segmented
      aliphatic polyurethanes of various chemical compositions and hydrophilic-to
      hydrophobic segment ratios. The scaffolds were implanted into monocortical
      defects in the iliac crest of healthy sheep for 6 months. The resected cortex was
      not repositioned. The ilium defects, which were not implanted with polyurethane
      scaffolds, were used as controls. In none of the control defects was there bone
      regeneration at the time of euthanasia. The defects implanted with porous
      scaffolds from polyurethanes were healed to varying extents with cancellous bone.
      The structure of the regenerated cancellous bone was radiographically denser than
      the structure of native bone. New bone that was formed in the scaffolds with a
      higher amount of hydrophilic component contained more calcium phosphate deposit
      than the bone formed in the scaffolds with a lower amount of the hydrophilic
      component. There was no new cortex formed over the defect, but a thin layer of
      soft tissue covered the newly formed cancellous bone.

PMID- 16960828
TI  - Comparative study between coral-mesenchymal stem cells-rhBMP-2 composite and auto
      bone-graft in rabbit critical-sized cranial defect model.
AB  - Tissue engineered bone has become a bone substitute for the treatment of bone
      defects in animal research. This study investigated the osteogenesis capacity of
      coral-MSCs-rhBMP-2 composite with the auto-bone-graft as control. Coral-MSCs
      rhBMP-2 composite were fabricated by coral (as main scaffold), rhBMP-2 (as growth
      factor), and MSCs (cultured from iliac marrow as seed cells). Critical-sized
      defects (d = 15 mm) were made on forty rabbits crania and treated by different
      composite scaffolds: iliac autograft (n = 8), coral (n = 8), rhBMP-2/coral (n =
      8), and MSCs/rhBMP-2/coral (n = 8). The defects were evaluated by gross
      observation, radiographic examination, histological examination, and histological
      fluorescence examinations after 8 and 16 weeks. The results showed that repair of
      bone defect was the least in coral group, and significant ingrowth of new bone
      formation and incorporation could be seen with 77.45% +/- 0.52% in radiopacity in
      MSCs/rhBMP-2/coral group, which was similar to that in iliac autograft group
      (84.61% +/- 0.56% in radiopacity). New bone formation in MSCs/rhBMP-2/coral group
      was more than that in rhBMP-2/coral group. And osteogenesis rate in MSCs/rhBMP
      2/coral group (10.23 +/- 1.45 microm) was much faster than that in rhBMP-2/coral
      group (5.85 +/- 2.19 microm) according to histological fluorescence examination.
      Newly formed bone partly came from induced MSCs in composite scaffold according
      to bromodeoxyuridine immunohistochemical examination. These data implicated that
      MSCs could produce synergic effect with coral-rhBMP-2, and the tissue engineered
      bone of coral-MSCs-rhBMP-2 is comparable to auto-bone-graft for the repair of
      critical-sized bone defect.

PMID- 16960829
TI  - Controlling the orientation of bone osteopontin via its specific binding with
      collagen I to modulate osteoblast adhesion.
AB  - Osteopontin (OPN) is an important matricellular protein that modulates cell
      functions. It is potentially an excellent surface-coating component for
      engineered biomaterials. It is believed that in its preferred orientation and
      conformation on a surface, the functional domains of OPN such as the arginine
      glycine-aspartic acid (RGD) motif will be presented to cells to the greatest
      extent. Previously, the authors demonstrated that OPN orientation could be
      modulated by surface charge. In this work, the authors attempt to control the
      orientation/conformation of bone OPN via its specific interactions with type I
      collagen. Surface plasmon resonance was used to confirm the specific binding
      between bone OPN and collagen I. A radiolabeled OPN adsorption assay was used to
      determine the amount of adsorbed OPN on tissue culture polystyrene (TCPS)
      surfaces with or without collagen I as an interlayer. An in vitro cell adhesion
      assay using osteoblast MC3T3-E1 was performed to compare the functionality of
      collagen-bound OPN and adsorbed OPN on TCPS. With the same amount of OPN on the
      surfaces, the number of cells adhered to collagen-bound OPN is significantly
      higher than to OPN alone on TCPS. A cell inhibition assay using soluble GRGDSP
      peptides showed that a higher GRGDSP concentration was needed to completely block
      osteoblast adhesion to collagen-bound OPN than to OPN directly on TCPS. Enhanced
      cell adhesion and higher blocking peptide concentration suggest that collagen
      bound bone OPN has a preferable orientation/conformation for cell adhesion
      compared with OPN alone on TCPS. Thus, the specific binding of OPN to collagen I
      may naturally orient OPN, thus influencing osteoblast adhesion.

PMID- 16960830
TI  - Numerical model for DNA loading in microdevices: stacking and autogating effects.
AB  - Many electrophoresis-based DNA sequencing and genotyping microdevices rely on
      field-driven effects to load and preconcentrate the sample. A quantitative model
      is developed for a broad class of electrophoresis-based microfabricated sample
      injectors. Quantitative predictions of DNA preconcentration are compared with
      experimental data and are shown to qualitatively reproduce the detailed time
      evolving sample distribution in the injector. The model provides practical
      guidance on device and protocol design, in order to optimize this critical aspect
      of microfluidic devices.

PMID- 16960831
TI  - Conjugates of poly(DL-lactide-co-glycolide) on amino cyclodextrins and their
      nanoparticles as protein delivery system.
AB  - Poly(DL-lactide-co-glycolide) (PLG) was chemically conjugated on two amino
      cyclodextrins, mono(6-(2-aminoethyl)amino-6-deoxy)-beta-cyclodextrin and
      ethylenediamino bridged bis(beta-cyclodextrin), to afford novel amphiphilic
      conjugates. Those conjugates were then characterized with infrared spectrometry
      (IR), proton nuclear magnetic resonance ((1)H NMR) and gel permeation
      chromatography (GPC). A repeat-nanoprecipitation (RP-NP) method was also
      developed to fabricate the nanoparticles of the conjugates with a water-soluble
      model protein, bovine serum albumin (BSA). At the end of RP-NP process, the
      availability of BSA was over 80% while the entrapment efficiency was 40-50% for
      each nanoprecipitation. The nanoparticles were rigid and spherical with diameters
      of 110-180 nm determined by transmission electron microscope (TEM), atomic force
      microscopy (AFM) and particle size analyzer. Nanoparticles possessed good steric
      stability during freeze-drying and resuspensions due to the existence of
      cyclodextrins corona. Interactions between BSA and the conjugates in the
      nanoparticles were then elucidated with IR experiments. About 25% BSA adsorbed on
      the surface of nanoparticles due to the interaction and was easy to release in
      the first day. The release of BSA from the nanoparticles was in three phases: a
      burst effect in the first day, a followed plateau in about a week, and a
      sustained release of the protein over 14 days. By changing the lactide/glycolide
      ratio, the degradation time of the conjugates and the release rate of BSA could
      be controlled. The loss of CDs content was faster than that of overall Mw during
      degradation since CDs formed outer corona of the nanoparticles. Both the novel
      biomaterials and the nanosphere fabrication technique contributed to the
      maintenance of protein structure.

PMID- 16960832
TI  - QSNPlite, a software system for quantitative analysis of SNPs based on capillary
      array SSCP analysis.
AB  - We present a newly developed software called "QSNPlite" that comprehensively
      interprets the data of SSCP and sequencing analyses obtained from capillary array
      electrophoresis systems used in the quantitative characterization of SNPs.
      QSNPlite assists in the genotyping of individuals with SNPs and in estimating the
      allele frequencies of SNPs using pooled DNA. We show that this estimation is
      accurate (mean absolute error, 1.4%) by comparing the results of the pooled
      analysis using QSNPlite with the true frequencies based on the allele counting
      after performing individual genotypings. The QSNPlite program runs on Windows XP
      and can be used to determine the allele frequencies of SNPs among a large number
      of individuals, such as in association studies of disease-responsible genes using
      the candidate gene approach.

PMID- 16960833
TI  - Induction of directional sprouting angiogenesis by matrix gradients.
AB  - The fate of any tissue engineering implant relies upon an adequate oxygen and
      nutrients supply throughout the cellular construct and, hence, by the ability of
      the scaffold to induce and guide vascular ingrowth. However, implant
      vascularization is usually an uncontrolled process that takes several weeks. In
      this work, we assessed the feasibility of controlling vascular sprout rate and
      direction within three-dimensional collagen-hyaluronic acid semi-interpenetrated
      networks by modulating the spatial distribution of the matricellular cues.
      Results indicated that increasing amount of hyaluronic acid (HA) within the
      matrix led to a progressive inhibition of sprouting. In HA-rich matrices, the
      sprout number and the propagation rate showed a 2.7- and 4-fold reduction,
      respectively, compared to collagen matrices. Furthermore, by creating HA
      gradients within the collagen network, we were able to direct and enhance the
      sprouting rate. This study provides an experimental platform for controlling
      vascularization of engineered tissues.

PMID- 16960834
TI  - Multiplex_QA: an exploratory quality assessment tool for multiplexed
      electrophoretic assays.
AB  - Multiplex_QA is a data analysis tool for visualizing short- and long-term changes
      in the performance of multiplexed electrophoretic assays, particularly the
      commercial short tandem repeat (STR) kits used by the human forensic identity
      community. A number of quality metrics are calculated from the signal collected
      for the internal size standard included in nearly all multiplex assays. These
      quality metrics are related to the signal intensity, symmetry, retention,
      resolution, and noise of data collected by capillary electrophoresis systems.
      Interlocking graphical displays enable the identification of changes in the
      quality metrics with time, evaluation of relationships among the metrics, and
      detailed examination of electropherographic features of particularly interesting
      analyses. While primarily intended for exploring which metrics are most useful
      for documenting data quality, the current version of the tool is sufficiently
      robust for use by forensic scientists with an interest in data analysis and
      access to a fast desktop computer.

PMID- 16960835
TI  - Surface modification of poly(methyl methacrylate) for improved adsorption of wall
      coating polymers for microchip electrophoresis.
AB  - The development of rapid and simple wall coating strategies for high-efficiency
      electrophoretic separation of DNA is of crucial importance for the successful
      implementation of miniaturized polymeric DNA analysis systems. In this report, we
      characterize and compare different methods for the chemical modification of
      poly(methyl methacrylate) (PMMA) surfaces for the application of wall coating
      polymers. PMMA surfaces coated with 40 mol% diethylacrylamide and 60 mol%
      dimethylacrylamide are compared to the PMMA surfaces first oxidized and then
      coated with hydroxypropylmethyl-cellulose or poly(vinyl alcohol) (PVA). PMMA
      oxidation was accomplished with UV/ozone or an aqueous solution of HNO(3) to
      yield hydrogen-bond donors for the spontaneous adsorption of the coating
      polymers. Contact angle measurements of UV/ozone exposed PMMA surfaces indicate
      increase in hydrophilicity, and polymer coated surfaces show a strong dependence
      on the coating polymer and the oxidation method. Fast and repeatable
      electrophoretic separations of a 10-base and 20-base DNA ladder were performed in
      PMMA micro CE devices. All analyses were completed in less than 10 min, resulting
      in the number of theoretical plates as high as 583 000 in a 7.7 cm long
      separation channel. The duration of UV/ozone treatment was found to have a
      considerable impact on separation performance. The microchips irradiated with UV
      for 10 min and coated with PVA as well as the microchips treated with HNO(3) and
      coated with HPMC were found to have the best separation performance. These
      results demonstrate facile and robust methods for the surface modification of
      PMMA enabling low-cost single use devices for electrophoretic DNA separations.

PMID- 16960836
TI  - Peri-implant bone formation and implant integration strength of peptide-modified
      p(AAM-co-EG/AAC) interpenetrating polymer network-coated titanium implants.
AB  - Interpenetrating polymer networks (IPNs) of poly (acrylamide-co-ethylene
      glycol/acrylic acid) functionalized with an -Arg-Gly-Asp- (RGD) containing 15
      amino acid peptides, derived from rat bone sialoprotein (bsp-RGD(15), were
      grafted to titanium implants in an effort to modulate bone formation in the peri
      implant region in the rat femoral ablation model. Bone-implant contact (BIC) and
      bone formation within the medullary canal were determined using microcomputed
      tomography at 2 and 4 weeks postimplantation. BIC for bsp-RGD(15)-IPN implants
      was enhanced relative to hydroxyapatite tricalcium phosphate (HA-TCP) coated
      implants, but was similar to all other groups. Aggregate bone formation neither
      indicated a dose-dependent effect of bsp-RGD(15) nor a meaningful trend.
      Mechanical testing of implant fixation revealed that only the HA-TCP coated
      implants supported significant (>1 MPa) interfacial shear strength, despite
      exhibiting lower overall BIC, an indication that bone ingrowth into the rougher
      coating was the primary mode of implant fixation. While no evidence was found to
      support the hypothesis that bsp-RGD(15)-modified IPN coated implants
      significantly impacted bone-implant bonding, these results point to the lack of
      correlation between in vitro studies employing primary osteoblasts and in vivo
      wound healing in the peri-implant region.

PMID- 16960837
TI  - DNA sequencing and multiplex STR analysis on plastic microfluidic devices.
AB  - The ability of plastic microfluidic devices with separation channel lengths of 6,
      10 or 18 cm to perform high-quality and high-performance ssDNA analysis was
      evaluated. Specifically, four-color DNA sequencing separation of a terminator
      sequencing standard using replaceable, urea-denaturing linear polyacrylamide
      (LPA) solution as a sieving matrix, yielded read lengths of 410 bases in 15 min
      with base calling accuracy of 99.2% on a 6-cm device, and 640 bases in 35 min
      with accuracy of 98.0% on a 18-cm device. A two-color sizing analysis of four
      locus (CSF1PO, TPOX, TH01, vWA) short tandem repeats (STRs) allelic ladder on a
      10-cm device indicated a mean SD of +/- 0.08 base pairs (bp) between runs, and
      single bp resolution of spiked TH01 allele 9.3 (198 bp) from TH01 allele 10 (199
      bp) of the CTTv ladder with R = 0.81. A four-color multiplex sizing analysis of
      three different AmpFlSTR allelic ladders consisting of nine loci (D3S1358, vWA,
      FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820) and gender alleles
      (Amelogenin) on a 10-cm device had a mean SD of +/- 0.15 bp between runs for
      sizing three loci, i.e., FGA, D18S51 and D3S818; alleles differing by 2 bp in
      size were resolved with resolutions close to baseline. This work demonstrates
      that plastic microfluidic devices are capable of quality sequencing and STR
      sizing comparable to that of glass devices of similar separation lengths.

PMID- 16960838
TI  - Genotyping of simple sequence repeats--factors implicated in shadow band
      generation revisited.
AB  - PCR amplification of microsatellite sequences generates, besides the main product
      corresponding to allele size, also additional, undesired products usually shorter
      by multiples of the repeated unit. These extra products known as shadow bands or
      stutter products may complicate genotyping. The mechanism by which these
      artifacts are formed is not well understood and so no effective remedy has been
      found to cope with these spurious products. In this study, using the DNA
      templates containing the CAG/CTG repeats flanked by gene-specific sequences and
      universal priming sites, we analyzed the effects of many PCR variables on the
      shadow band generation. The most important result was that at the decreased
      temperature of the denaturation step during PCR cycling the shadow bands were
      either not formed or were strongly suppressed. Several possible sources of this
      effect are discussed.

PMID- 16960839
TI  - Acrylic bone cements with bismuth salicylate: Behavior in simulated physiological
      conditions.
AB  - In a previous work, we reported the development of acrylic bone cement
      formulations for application in percutaneous vertebroplasty, by using bismuth
      salicylate (BS) as the radiopaque agent. Our objective was to obtain high
      radiopacity along with a therapeutical effect produced by the release of
      salicylic acid in situ. To follow that study, the setting kinetics and static and
      dynamical mechanical properties of the BS cements were studied in simulated
      physiological conditions. Moreover, radiopacity after various times of immersion
      in saline and the wettability of the cements surfaces were determined. The study
      finished with the analysis of the biological response. From the results, it can
      be concluded that physiological conditions did not affect negatively to the
      cements performance, since all BS-loaded cements fulfilled the ISO standard
      requirements. Radiopacity of the formulations was maintained over time and
      cements with BS were found to be biocompatible.

PMID- 16960840
TI  - A robust cross-linked polyacrylamide coating for microchip electrophoresis of
      dsDNA fragments.
AB  - Surface derivatization plays an important role in microchip electrophoresis. It
      not only enhances the resolution, but also improves the reproducibility. So far,
      the most popularly used derivatization method for glass microchannels is to
      covalently attach a layer of linear polyacrylamide (LPA) to the channel surfaces.
      However, LPA coating has two problems: incomplete coverage and limited lifetime.
      To address these issues, we have recently developed a cross-linked polyacrylamide
      (CPA) derivatization protocol and demonstrated it for high-resolution protein
      separations by CIEF, CGE, and CZE. In this report, we used this protocol to coat
      microchip channels and exhibited the reliability and robustness of CPA coating
      for microchip electrophoresis of DNA molecules. dsDNA fragments were used as our
      test samples. High resolutions were obtained for fragments ranging from 100 bp to
      10 kpb. After more than 800 runs, the CPA-coated microchannels still performed
      well and comparable resolutions were maintained throughout these runs.

PMID- 16960841
TI  - A precise mRNA quantification method using CE-based SSCP.
AB  - Even though mRNA quantification provides significant information for biological
      analysis, current methods such as Northern blot analysis and real-time PCR are
      known to be laborious and lacking in precision. In this study, we demonstrate a
      new precise mRNA quantification method using CE based on SSCP (CE-SSCP) coupled
      with reverse transcription. mRNA samples could be simply analyzed for the
      quantification directly with reverse transcript obtained from a single reaction.
      This helps to avoid considerable errors generated by a series of the tedious
      manual steps. Also, unlike real-time PCR, reverse transcripts can be directly
      quantified by CE-SSCP in this method without further data estimation.
      Reproducibility and accuracy of CE-SSCP for mRNA quantification was examined
      using enhanced green fluorescent protein (eGFP) mRNA transcribed in vitro.
      Specific reverse transcription primer was determined for the accurate
      quantification of eGFP mRNA from total RNA obtained from the recombinant
      Escherichia coli. Using elongation factor Tu mRNA as an internal standard, it was
      shown that sample-to-sample variation could be minimized. Expression kinetics at
      both mRNA level and protein level was studied and the potential of CE-SSCP in
      expression analysis was demonstrated by comparison with the eGFP activity assay.

PMID- 16960842
TI  - Do-it-yourself microelectrophoresis chips with integrated sample recovery.
AB  - We present a microelectrophoresis chip that is simple to fabricate using the
      microfluidic tectonics (microFT) platform (Beebe, D. J. et al., Proc. Natl. Acad.
      Sci. USA 2000, 97, 13488-13493; Agarwal, A. K. et al.,. J. Micromech. Microeng.
      2006, 16, 332-340). The device contains a removable capillary insert (RCI) for
      easy sample collection after separation (Atencia, J. et al.,. Lab Chip 2006, DOI:
      10. 1039/b514068d). Device construction is accomplished in less than 20 min
      without specialized equipment traditionally associated with microelectrophoresis
      chip construction. microFT was used to build a PAGE device utilizing two
      orthogonal microchannels. One channel performs standard separations, while the
      second channel serves as an access point to remove bands of interest from the
      chip via the RCI. The RCI contains an integrated electrode that facilitates the
      removal of bands using electrokinetic techniques. The device was characterized
      using prestained proteins (Pierce BlueRanger and TriChromRanger). Samples were
      loaded into the microelectrophoresis device via a standard micropipette. An
      electrical field of 40 V/cm was used to separate and collect the proteins. The
      microPAGE device is simple to fabricate, benefits from microscale analysis, and
      includes an on-chip collection scheme that interfaces the macroworld with the
      microworld.

PMID- 16960843
TI  - Scale-up development of high-performance polymer matrix for DNA sequencing
      analysis.
AB  - Linear polyacrylamide (LPA) has been widely used as a replaceable separation
      matrix in CE. An increase in the molecular weight of the separation medium favors
      the separation of larger DNA fragments. In order to obtain ultrahigh-molecular
      weight (UHMW) LPA, a "frozen" method was developed to synthesize the LPA
      homopolymer. This approach has three major advantages when compared with other
      existing routes of LPA synthesis: (i) long LPA chains could be obtained easily,
      with their average molecular weight (MW) being in the high 10 MDa range; (ii) the
      desired MW could be adjusted over a broad range by controlling the temperature
      and the concentration of initiators during synthesis; (iii) the product solution
      contains only a tiny amount of impurity besides the solvent and LPA. Both static
      and dynamic laser light scattering measurements were carried out to characterize
      the synthesized LPA in the buffer solution. The DNA sequencing matrix prepared
      from LPA using this method was studied and the results were compared with the
      newly developed commercial product POP7 from Applied Biosystems. It should be
      noted that this approach can be applied to synthesize other water-soluble
      polymers, resulting in UHMW products because the chain transfer constant is
      smaller at lower temperatures.

PMID- 16960844
TI  - An improved gel-based DNA microarray method for detecting single nucleotide
      mismatch.
AB  - 3-D polyacrylamide gel-based DNA microarray platforms provide a high capacity for
      nucleic acids immobilization and a solution-mimicking environment for
      hybridization. However, several technological bottlenecks still remain in these
      platforms, such as difficult microarray preparation and high fluorescent
      background, which limit their application. In this study, two new approaches have
      been developed to improve the convenience in microarray preparation and to reduce
      the background after hybridization. To control the polymerization process,
      solutions containing acrylamide-modified oligonucleotide, acrylamide, glycerol
      and ammonium persulfate are spotted onto a functionalized glass slide, and then
      the slide is transferred to a vacuum chamber with TEMED, so that TEMED is
      vaporized and diffused into the spots to induce polymerization. By applying an
      electric field across a hybridized microarray to remove the nonspecifically bound
      labeled targets, this approach can solve the problem of high fluorescent
      background of the gel-based microarray after hybridization. Experimental results
      show that our immobilization method can be used to construct high quality
      microarrays and exhibits good reproducibility. Moreover, the polymerization is
      not affected by PCR medium, so that PCR products can be used for microarray
      construction without being treated by commercial purification cartridges.
      Electrophoresis can improve the signal-to-noise significantly and has the ability
      to differentiate single nucleotide variation between two homozygotes and a
      heterozygote. Our results demonstrated that this is a reliable novel method for
      high-throughput mutation analysis and disease diagnosis.

PMID- 16960845
TI  - Automated screening using microfluidic chip-based PCR and product detection to
      assess risk of BK virus-associated nephropathy in renal transplant recipients.
AB  - The cost-effective detection of viral particles in bodily fluids could enable
      more effective responses to viral outbreaks, whether isolated clinical cases, or
      influenza epidemics. In renal transplant recipients, complications arising from
      high levels of BK virus can lead to graft dysfunction, graft loss, and/or reduced
      patient survival. We describe a microfluidic system for the sensitive analysis of
      BK virus (viral load) in unprocessed urine samples that are applied directly onto
      the chip, thus avoiding labor-intensive processing and sources of inter-assay
      variability. Integration of small volume genetic amplification (PCR) and
      electrophoretic analysis detects as few as 1-2 viral copies, distinguishes
      between high, medium and low levels of virus and reliably identifies viral loads
      requiring clinical intervention. As a first step to wider application in the
      clinic and in the field, the present work presents an entirely microchip-based
      system, validated against conventional clinical methods using clinical samples.

PMID- 16960847
TI  - Graded pairs comparison - does strength of preference matter? Analysis of
      preferences for specialised nurse home visits for pain management.
AB  - In the stated preference method called graded pairs comparisons respondents are
      asked to rate the intensity of their preference for their preferred alternative
      in a pairwise comparison of alternatives. Econometricians anticipate that the
      additional information will improve statistical efficiency compared to the
      standard DCE format. However, this paper reveals that added information inherent
      in graded pairs scale does not provide smaller standard deviations for the WTP
      estimated. Secondly, the ordered-response regression models employing the full
      range of the graded pairs data tend to overestimate WTP, which presumably is
      caused by the inherent tendency of the ordered-response models to 'predict to the
      extremes'.

PMID- 16960846
TI  - Multiplex primer extension analysis for rapid detection of major European
      mitochondrial haplogroups.
AB  - The evolution of the human mitochondrial genome is reflected in the existence of
      ethnically distinct lineages or haplogroups. Alterations of mitochondrial DNA
      (mtDNA) have been instrumental in studies of human phylogeny, in population
      genetics, and in molecular medicine to link pathological mutations to a variety
      of human diseases of complex etiology. For each of these applications, rapid and
      cost effective assays for mtDNA haplogrouping are invaluable. Here we describe a
      hierarchical system for mtDNA haplogrouping that combines multiplex PCR
      amplifications, multiplex single-base primer extensions, and CE for analyzing ten
      haplogroup-diagnostic mitochondrial single nucleotide polymorphisms. Using this
      rapid and cost-effective mtDNA genotyping method, we were able to show that
      within a large, randomly selected cohort of healthy Austrians (n = 1172), mtDNAs
      could be assigned to all nine major European haplogroups. Forty-four percent
      belonged to haplogroup H, the most frequent haplogroup in European Caucasian
      populations. The other major haplogroups identified were U (15.4%), J (11.8%), T
      (8.2%) and K (5.1%). The frequencies of haplogroups in Austria is within the
      range observed for other European countries. Our method may be suitable for
      mitochondrial genotyping of samples from large-scale epidemiology studies and for
      identifying markers of genetic susceptibility.

PMID- 16960848
TI  - Current in vivo wear of metal-on-metal bearings assessed by exercise-related rise
      in plasma cobalt level.
AB  - Baseline metal ion levels are elevated in patients with metal-on-metal (MOM) hip
      arthroplasty. Interpretation of baseline levels is difficult as measurements are
      influenced by wear, corrosion, and metal ion release from stored metal in the
      body. Schmalzried et al. demonstrated that "wear is the function of use, not
      time." The specific research question we asked was: Does physiological exercise
      increase the wear of metal-on-metal articulation which can be measured from the
      plasma metal ion levels? Patients with three different well functioning MOM
      bearings [two types of resurfacing (BHR 46.8 mm and Cormet 48 mm) and Metasul 28
      mm] were included. Blood samples were taken immediately before, immediately
      after, and 1 h after exercise to determine cobalt and chromium levels. A
      significant increase (p<0.005) in serum cobalt and chromium of 13% and 11%,
      respectively, was noticed after the exercise. Rise of cobalt levels in patients
      with a resurfacing MOM was 8.5 times (BHR group) or 6.5 times (Cormet group)
      larger than in those with a Metasul MOM (p=0.021 and p=0.047). Neither rise of
      metal levels nor baseline levels correlated with any other factor (p>0.27).
      Exercise-related elevations of plasma cobalt level provides information on
      current in vivo wear production that cannot be inferred from a baseline
      measurement of cobalt levels. Chromium levels cannot provide reliable information
      on the in vivo wear of the devices. Diameter was the important feature of the
      implant in determining exercise-related elevations of plasma cobalt level.
      Exercise-related elevations of plasma cobalt level is a potential in vivo tool to
      understand and improve the tribology of metal-metal bearings.

PMID- 16960849
TI  - Molecular approaches in the diagnosis of primary immunodeficiency diseases.
AB  - Over 120 inherited primary immunodeficiency diseases (PIDs) are known to exist.
      The genes responsible for many of these diseases have also been identified.
      Recent advances in diagnostic procedures have enabled these to be identified
      earlier and appropriately treated. While a number of approaches are available to
      identify mutations, direct sequencing remains the gold standard. This approach
      identifies the exact genetic change with substantial precision. We suggest that a
      sensitive and economical approach to mutation detection could be the direct
      sequencing of cDNA followed by the confirmatory sequencing of the corresponding
      exon. While screening techniques such as single-stranded conformation
      polymorphism (SSCP), heteroduplex analysis (HA), denaturing gradient gel
      electrophoresis (DGGE), and denaturing high-performance liquid chromatography
      (dHPLC) have proven useful, each has inherent advantages and disadvantages. We
      discuss these advantages and disadvantages and also discuss the potential of
      future sequencing technologies such as pyrosequencing, combinatorial sequencing
      by-hybridization, multiplex polymerase colony (polony), and resequencing arrays
      as tools for future mutation detection. In addition we briefly discuss several
      high-throughput SNP detection technologies.

PMID- 16960850
TI  - Does the economy affect teenage substance use?
AB  - This research examines how teenage drug and alcohol use responds to changes in
      the economy. In contrast to the recent literature confirming pro-cyclical alcohol
      use among adults, this research offers strong evidence that a weaker economy
      leads to greater teenage marijuana and hard-drug use and some evidence that a
      weaker economy also leads to higher teenage alcohol use. The findings are based
      on logistic models with state and year fixed effects, using teenagers from the
      NLSY-1997. The evidence also indicates that teenagers are more likely to sell
      drugs in weaker economies. This suggests one mechanism for counter-cyclical drug
      use - that access to illicit drugs is easier when the economy is weaker. These
      results also suggest that the strengthening economy in the 1990s mitigated what
      would otherwise have been much larger increases in teenage drug use.

PMID- 16960851
TI  - Seeing the NICE side of cost-effectiveness analysis: a qualitative investigation
      of the use of CEA in NICE technology appraisals.
AB  - Resource scarcity is the raison d'etre for the discipline of economics. Thus, the
      primary purpose of economic analysis is to help decision-makers when addressing
      problems arising due to the scarcity problem. The research reported here was
      concerned with how cost-effectiveness information is used by the National
      Institute for Health & Clinical Excellence (NICE) in national technology coverage
      decisions in the UK, and how its impact might be increased. The research followed
      a qualitative case study methodology with semi-structured interviews, supported
      by observation and analysis of secondary sources. Our research highlights that
      the technology appraisal function of NICE represents an important progression for
      the UK health economics community: new cost-effectiveness work is commissioned
      for each technology and that work directly informs national health policy.
      However, accountability in policy decisions necessitates that the information
      upon which decisions are based (including cost-effectiveness analysis, CEA) is
      accessible. This was found to be a serious problem and represents one of the main
      ongoing challenges. Other issues highlighted include perceived weaknesses in
      analysis methods and the poor alignment between the health maximisation
      objectives assumed in economic analyses and the range of other objectives facing
      decision-makers in reality.

PMID- 16960852
TI  - RAG-dependent primary immunodeficiencies.
AB  - Mutations in recombination activating genes 1 and 2 (RAG1 and RAG2) cause a
      spectrum of severe immunodeficiencies ranging from classical T cell-B cell-severe
      combined immunodeficiency (T(-)B(-)SCID) and Omenn syndrome (OS) to an increasing
      number of peculiar cases. While it is well established from biochemical data that
      the specific genetic defect in either of the RAG genes is the first determinant
      of the clinical presentation, there is also increasing evidence that
      environmental factors play an important role and can lead to a different
      phenotypic expression of a given genotype. However, a better understanding of the
      mechanisms by which the molecular defect impinges on the cellular phenotype of OS
      is still lacking. Ongoing studies in knock-in mice could better clarify this
      aspect.

PMID- 16960854
TI  - Intention tremor of the head in patients with essential tremor.
AB  - Patients with essential tremor (ET) have kinetic arm tremor; this tremor can also
      have an intentional component. We are unaware of reports of intention tremor of
      the head in ET. Our aims were to describe, provide electrophysiological data and
      video documentation of, and estimate the prevalence of intention tremor of the
      head in our sample. Ten (9.0%; 95% confidence interval = 4.7%-14.3%) of 111
      patients had intention tremor of the head; in 7 it involved the neck and in 3 the
      chin. These patients trended toward having more severe kinetic arm tremor and
      they had more severe intention tremor of the arms. These observations provide
      further support for the evolving view that the cerebellum may be involved in ET.

PMID- 16960855
TI  - Metodopramide-induced palatopharyngeal myoclonus.

PMID- 16960853
TI  - Functional neuroimaging studies in posttraumatic stress disorder: review of
      current methods and findings.
AB  - Posttraumatic stress disorder (PTSD) is an anxiety disorder associated with
      changes in neural circuitry involving frontal and limbic systems. Altered
      metabolism in these brain structures after a traumatic event is correlated to
      PTSD. Developments in the field of neuroimaging have allowed researchers to look
      at the structural and functional properties of the brain in PTSD. Despite the
      relative novelty of functional imaging and its application to the field of PTSD,
      numerous publications have brought to light several of the circuits implied in
      this disorder. This article summarizes the findings with regard to PTSD in the
      functional imaging techniques of single-photon emission computed tomography
      (SPECT), positron emission tomography (PET), and functional magnetic resonance
      imaging (fMRI). Furthermore, we discuss strengths and weaknesses of the various
      techniques and studies. Finally, we explore the future potential of functional
      neuroimaging studies in PTSD.

PMID- 16960856
TI  - Phases of myogenic cell activation and possible role of dermomyotome cells in
      teleost muscle formation.
AB  - Present knowledge indicates that fibre recruitment (hyperplasia) in developing
      teleost fish occurs in three distinct phases. However, the origin and
      relationship of the myogenic precursors activated during the different phases
      remains unclear. Here, we address this issue using molecular techniques on
      embryos and larvae of pearlfish, a large cyprinid species. Results provide
      comprehensive molecular characterisation of cell recruitment over the three
      phases of myogenesis, identifying muscle types as they arise. Specifically, we
      show that the myogenic cells arising during 2nd phase myogenesis are clearly
      different from the myogenic cells arising during the 3rd phase and that the
      dermomyotome is a major source of myogenic cells driving 2nd phase hyperplasia.
      These findings are discussed in relation to their implications for the generality
      of vertebrate developmental patterns.

PMID- 16960858
TI  - Tardive blepharospasm beginning after withdrawal of veralipride.

PMID- 16960857
TI  - Analysis of pattern precision shows that Drosophila segmentation develops
      substantial independence from gradients of maternal gene products.
AB  - We analyze the relation between maternal gradients and segmentation in
      Drosophila, by quantifying spatial precision in protein patterns. Segmentation is
      first seen in the striped expression patterns of the pair-rule genes, such as
      even-skipped (eve). We compare positional precision between Eve and the maternal
      gradients of Bicoid (Bcd) and Caudal (Cad) proteins, showing that Eve position
      could be initially specified by the maternal protein concentrations but that
      these do not have the precision to specify the mature striped pattern of Eve. By
      using spatial trends, we avoid possible complications in measuring single
      boundary precision (e.g., gap gene patterns) and can follow how precision changes
      in time. During nuclear cleavage cycles 13 and 14, we find that Eve becomes
      increasingly correlated with egg length, whereas Bcd does not. This finding
      suggests that the change in precision is part of a separation of segmentation
      from an absolute spatial measure, established by the maternal gradients, to one
      precise in relative (percent egg length) units.

PMID- 16960859
TI  - The ADH1C stop mutation in multiple system atrophy patients and healthy probands
      in the United Kingdom and Germany.

PMID- 16960860
TI  - Correlation between cardiac 123I-MIBG and odor identification in patients with
      Parkinson's disease and multiple system atrophy.
AB  - We investigated an association between olfaction and cardiac (123)I
      metaiodobenzylguanidine (MIBG) uptake in patients with Parkinson's disease (PD)
      and multiple system atrophy (MSA). There was a significant positive correlation
      between cardiac MIBG uptake and the Cross-Cultural Smell Identification (CCSI)
      score in patients with PD (r = 0.56; P = 0.003) independent of the disease
      duration or clinical rating of motor status. However, patients with MSA did not
      show a significant correlation between cardiac MIBG uptake and the CCSI score.
      Our findings suggest that the functional losses of the olfactory and cardiac
      sympathetic systems are closely coupled in PD.

PMID- 16960861
TI  - Prevalence of primary blepharospasm in Sardinia, Italy: a service-based survey.
AB  - We performed a service-based epidemiological study of primary blepharospasm in
      the island of Sardinia (Italy). Due to its favorable geographical location, we
      are confident we will provide reliable data from patients seeking botulinum toxin
      treatment. A total of 53 patients were assessed. Prevalence was estimated to be
      32.2 per 1 million (95% confidence interval, 23.0-40.8). These results are in
      line with those obtained in other similar surveys, that is, record-based, and
      performed in various European regions such as Northern England, the Munich area,
      as well as the Epidemiologic Study of Dystonia in Europe.

PMID- 16960862
TI  - Pharmacological characterization of psychosis-like behavior in the MPTP-lesioned
      nonhuman primate model of Parkinson's disease.
AB  - Investigation of the pathophysiology of psychosis in Parkinson's disease (PD), as
      well as the assessment of potential novel therapeutics, has been limited by the
      lack of a well-validated animal model. MPTP-lesioned primates exhibit abnormal
      behaviors that are distinct from dyskinesia and parkinsonism and may represent
      behavioral correlates of neural processes related to psychosis in PD. Here we
      assess four types of behavior--agitation, hallucinatory-like responses to
      nonapparent stimuli, obsessive grooming, and stereotypies that are termed
      "psychosis-like"--and define their pharmacology using a psychosis-like behavior
      rating scale. By assessing the actions of drugs known to enhance or attenuate
      psychosis in PD patients, we find that the pharmacology of these behaviors
      recapitulates, in several respects, the pharmacology of psychosis in PD. Thus,
      levodopa and apomorphine elicited psychosis-like behaviors. Amantadine
      significantly decreased levodopa-induced dyskinesia but exacerbated psychosis
      like behaviors. Haloperidol reduced psychosis-like behaviors but at the expense
      of increased parkinsonian disability while the atypical neuroleptics clozapine
      and quetiapine reduced psychosis-like behaviors without significant effect on
      parkinsonian disability. The response of different components of the
      psychotomimetic behavior suggested the involvement of both dopaminergic and
      nondopaminergic mechanisms in their expression.

PMID- 16960863
TI  - Effects of rivastigmine in patients with and without visual hallucinations in
      dementia associated with Parkinson's disease.
AB  - We aimed to determine prospectively whether rivastigmine, an inhibitor of
      acetylcholinesterase and butyrylcholinesterase, provided benefits in patients
      with and without visual hallucinations in a population with dementia associated
      with Parkinson's disease (PDD). This was a 24-week double-blind placebo
      controlled study. Primary efficacy measures were the Alzheimer's Disease
      Assessment Scale cognitive subscale (ADAS-cog) and Alzheimer's Disease
      Cooperative Study-Clinician's Global Impression of Change (ADCS-CGIC). Secondary
      efficacy measures included activities of daily living, behavioral symptoms, and
      executive and attentional functions. Patients were stratified according to the
      presence of visual hallucinations at baseline. The study included 188 visual
      hallucinators (118 on rivastigmine, 70 on placebo) and 348 nonvisual
      hallucinators (239 on rivastigmine, 109 on placebo). Rivastigmine provided
      benefits in both visual hallucinators and nonvisual hallucinators. Absolute
      responses to rivastigmine on the ADAS-cog were comparable over 6 months, although
      rivastigmine-placebo differences tended to be larger in visual hallucinators
      (4.27; P = 0.002) than in nonhallucinators (2.09; P = 0.015). On the ADCS-CGIC,
      differences between rivastigmine and placebo were 0.5 in visual hallucinators (P
      = 0.030) and 0.3 in nonhallucinators (P = 0.111). Rivastigmine provided benefits
      on all secondary efficacy measures, and placebo declines and treatment
      differences were more marked in visual hallucinators. Adverse events were
      reported more frequently by rivastigmine-treated patients, although this
      difference was less marked in visual hallucinators. Visual hallucinations appear
      to predict more rapid decline and possibly greater therapeutic benefit from
      rivastigmine treatment in PDD.

PMID- 16960864
TI  - Unilateral positive-negative myoclonus in Creutzfeldt-Jakob disease.
AB  - We report a patient with Creutzfeldt-Jakob disease who presented asymmetric
      myoclonus. Positive-negative myoclonus was seen only in the right extremities in
      association with periodic synchronous discharges (PSDs) on the
      electroencephalogram, although pure positive myoclonus was rarely seen in the
      left extremities, independently in PSDs. The duration of the silent period
      recorded in the right-hand muscle produced by transcranial magnetic stimulation
      was much longer than that in the left-hand muscle or that in normal subjects.
      Brain MRI diffusion-weighted images showed signal hyperintensities in the putamen
      and cerebral cortex, including the motor cortex, predominantly on the left side.

PMID- 16960865
TI  - Relation of cerebral small-vessel disease and brain atrophy to mild Parkinsonism
      in the elderly.
AB  - The association between cerebral small-vessel disease, brain atrophy, and the
      risk and severity of mild parkinsonian signs (MPS) remains unclear. The objective
      of this study is to examine the effect of lacunar brain infarcts, cerebral white
      matter lesions (WMLs), and cortical atrophy on the risk and severity of MPS. This
      study is a cross-sectional community-based cohort study comprising 268 subjects,
      65 to 83 years of age, residing in the Augsburg region of southern Germany, and
      without contraindications for magnetic resonance imaging (MRI) of the brain. Main
      outcome measures. Subcortical and periventricular WMLs, lacunar brain infarcts,
      and cortical atrophy determined using a standardized MRI protocol developed for
      the Rotterdam Scan Study and an established rating scale. MPS, assessed in a
      standardized neurological examination and based on the Unified Parkinson's
      Disease Rating Scale motor scale. Lacunar brain infarcts and large subcortical
      white matter lesions were associated with an elevated risk of resting tremor.
      More severe cortical atrophy was related to an increased risk of rigidity and
      bradykinesia. In a linear regression analysis relating each individual MRI
      measurement with the severity of MPS, the number of lacunar brain infarcts and
      the degree of brain atrophy were correlated with the severity of resting tremor,
      whereas the size of subcortical and periventricular WMLs was correlated with the
      severity of rigidity. A higher degree of brain atrophy was associated with
      increased severity of either cardinal sign. In our study, presence and volume of
      lacunar brain infarcts, cerebral WMLs, and cortical atrophy were associated with
      the risk as well as severity of MPS. Determining the presence of these brain
      changes using brain imaging might contribute to identify persons at risk for MPS.

PMID- 16960866
TI  - NF-kB inhibition as a strategy to enhance etoposide-induced apoptosis in K562
      cell line.
AB  - NF-kB is a transcription factor that mediates antiapoptotic signals in several
      cancer cell lines. Here we have demonstrated that the cytotoxic drug, Etoposide,
      activates NF-kB in K562, a chronic myeloid leukemia blast crisis cell line.
      Treatment with the NF-kB inhibitors MG-132, Bay11-7082, and Resveratrol impedes
      Etoposide-induced NF-kB activation, rendering K562 sensitive to Etoposide-induced
      apoptosis. Stable expression of mutant form of IkB-alpha, which retains NF-kB
      inactive in the cytoplasm of cells, confirmed the data obtained with molecular
      inhibitors. Both inhibitors and stable expression of SR-IkB are associated with
      down-modulation of the antiapoptotic protein Bcl-xL, suggesting that the survival
      pathway activated by Etoposide involves NF-kB-mediated Bcl-xL expression.

PMID- 16960867
TI  - Reversible myelofibrosis associated with hemophagocytic lymphohistiocytosis.

PMID- 16960868
TI  - No adverse effect of vincristine on handwriting in children after completion of
      therapy.
AB  - BACKGROUND: Long-term writing difficulties in children after treatment with
      vincristine for acute lymphoblastic leukemia, Wilms tumor, B non-Hodgkin
      lymphoma, and malignant mesenchymal tumors, were investigated. PROCEDURE:
      Handwriting of 33 survivors and 33 controls matched for age, sex, and grade, was
      assessed with the BHK-scale. The examiner was blinded for whether a child was a
      case or a control. RESULTS: No significant difference in writing speed was found.
      Mean difference in number of letters produced during 5 min was 6.4 (+/-67.1,
      range -103 to +169). No significant difference was found in quality of writing
      scores; mean difference in points was 1.5 (+/-7.7, range -19 to +22). Cumulative
      vincristine dose, age at diagnosis or time since completion of treatment did not
      affect writing speed or quality. CONCLUSION: Chemotherapy, including vincristine,
      does not lead to long-term problems in speed or quality of writing in children
      treated for cancer.

PMID- 16960869
TI  - ABO incompatible stem cell transplantation in children does not influence
      outcome.
AB  - BACKGROUND: Although delayed red cell engraftment and/or hemolysis have been
      thoroughly documented in association with ABO incompatibility between donor and
      recipient in patients undergoing hematopoietic stem cell transplantation (HSCT),
      there are no studies defining the general, long term clinical outcome in a large
      group of pediatric patients. METHODS: We undertook a retrospective single center
      analysis of children undergoing pediatric allogeneic stem cell transplantation to
      determine the influence of ABO donor/recipient incompatibility. Outcome was
      analyzed according to donor type and included survival, graft versus host disease
      (GvHD), relapse, days of infection, antibiotic use, transfusion requirement and
      duration of hospital stay. RESULTS: Two hundred and sixteen children (136 males;
      80 females, aged 0-19) transplanted between January 1992 and December 2003 were
      included in the study. Indications for transplantation were hematological
      malignancies (n=179) and aplastic conditions (n=37). ABO compatibility was
      documented in 121 donor/recipient pairs. ABO incompatibility was documented in 95
      donor/recipient pairs with 40 major, 40 minor and 15 bi-directional incompatible
      pairs. ABO incompatibility did not influence survival rate (P=0.3762), the
      incidence of GvHD (P=0.253) or rate of relapse (P=0.930). Recovery of leucocytes
      was influenced by ABO incompatibility (P=0.0493), but the rate of infection,
      transfusion requirements and duration of hospital stay are not. CONCLUSION: In
      the pediatric setting, ABO major and/or minor mismatch between donor and
      recipient did not significantly influence the outcome of HSCT. The choice of
      donor should be determined by the degree of HLA match and CMV status in
      preference to ABO blood group compatibility.

PMID- 16960870
TI  - The beta3 chain short arm of laminin-332 (laminin-5) induces matrix assembly and
      cell adhesion activity of laminin-511 (laminin-10).
AB  - The basement membrane (BM) protein laminin-332 (Lm332) (laminin-5) has unique
      activity and structure as compared with other laminins: it strongly promotes
      cellular adhesion and migration, and its alpha3, beta3, and gamma2 chains are all
      truncated in their N-terminal regions (short arms). In the present study, we
      investigated the biological function of the laminin beta3 chain. When the beta3
      chain short arm (beta3SA) was overexpressed in HEK293 cells (beta3SA-HEK), they
      deposited a large amount of beta3SA and a small amount of laminin-511 (Lm511)
      (laminin-10) on culture plates. Control HEK293 cells secreted Lm511 but failed to
      deposit it. The extracellular matrix (ECM) deposited by beta3SA-HEK cells
      strongly promoted cell attachment and spreading. The beta3SA-HEK ECM did not
      directly bind Lm511, but it stimulated control HEK293 cells to deposit Lm511 on
      the culture plates. Although purified beta3SA did not support cell adhesion by
      itself, it enhanced the cell adhesion activity of Lm511. Experiments with anti
      integrin antibodies also suggested that the strong cell adhesion activity of the
      beta3SA-HEK ECM was derived from the synergistic action of beta3SA and Lm511. It
      has previously been found that beta3SA binds an unknown cell surface receptor.
      Taken together, the present study suggests that the short arm of the laminin
      beta3 chain enhances the matrix assembly of Lm511 and its cell adhesion activity
      by interacting with its receptor.

PMID- 16960871
TI  - PSM/SH2-B distributes selected mitogenic receptor signals to distinct components
      in the PI3-kinase and MAP kinase signaling pathways.
AB  - The Pro-rich, PH, and SH2 domain containing mitogenic signaling adapter PSM/SH2-B
      has been implicated as a cellular partner of various mitogenic receptor tyrosine
      kinases and related signaling mechanisms. Here, we report in a direct comparison
      of three peptide hormones, that PSM participates in the assembly of distinct
      mitogenic signaling complexes in response to insulin or IGF-I when compared to
      PDGF in cultured normal fibroblasts. The complex formed in response to insulin or
      IGF-I involves the respective peptide hormone receptor and presumably the
      established components leading to MAP kinase activation. However, our data
      suggest an alternative link from the PDGF receptor via PSM directly to MEK1/2 and
      consequently also to p44/42 activation, possibly through a scaffold protein. At
      least two PSM domains participate, the SH2 domain anticipated to link PSM to the
      respective receptor and the Pro-rich region in an association with an
      unidentified downstream component resulting in direct MEK1/2 and p44/42
      regulation. The PDGF receptor signaling complex formed in response to PDGF
      involves PI 3-kinase in addition to the same components and interactions as
      described for insulin or IGF-I. PSM associates with PI 3-kinase via p85 and in
      addition the PSM PH domain participates in the regulation of PI 3-kinase
      activity, presumably through membrane interaction. In contrast, the PSM Pro-rich
      region appears to participate only in the MAP kinase signal. Both pathways
      contribute to the mitogenic response as shown by cell proliferation, survival,
      and focus formation. PSM regulates p38 MAP kinase activity in a pathway unrelated
      to the mitogenic response.

PMID- 16960872
TI  - Nuclear myosin I is necessary for the formation of the first phosphodiester bond
      during transcription initiation by RNA polymerase II.
AB  - The nuclear isoform of myosin, Nuclear Myosin I (NMI) is involved in
      transcription by RNA polymerase I. Previous experiments showing that antibodies
      to NMI inhibit transcription by RNA polymerase II using HeLa cell nuclear extract
      (NE) suggested that NMI might be a general transcription factor for RNA
      polymerases. In this study we used a minimal in vitro transcription system to
      investigate the involvement of NMI in transcription by RNA polymerase II in
      detail. We demonstrate that NMI co-purifies with RNA polymerase II and that NMI
      is necessary for basal transcription by RNA polymerase II because antibodies to
      NMI inhibit transcription while adding NMI stimulates transcription. Further
      investigation revealed that NMI is specifically involved in transcription
      initiation. Finally, by employing an abortive transcription initiation assay, we
      demonstrate that NMI is crucial for the formation of the first phosphodiester
      bond during transcription initiation.

PMID- 16960873
TI  - Effects of a vitamin D3 analog on diabetes in the bio breeding (BB) rat.
AB  - Non-hypercalcemic analogs of vitamin D(3) modulate the immune response through
      antigen-presenting cells (APCs) and activated T-cells. A large population-base
      case-control showed that vitamin D(3) intake significantly decreases the risk of
      type 1 diabetes development. The aim of this study was, therefore, to observe the
      in vivo effects of a vitamin D(3) analog administered to Bio Breeding (BB) rats.
      1,25-Dihydroxy-16,23Z-diene-26,27-hexafluoro-19-nor vitamin D(3) (BXL-219,
      formerly Ro 26-2198) (BioXell, Milan, Italy) was administered in vivo to BB rats
      from days 42 to 110 of life at 0.2 microg/Kg BW. Control animals received only
      vehicle (olive oil, 4.8 microl/100 g BW). The animals of these two groups were
      subjected to insulin treatment as they became diabetic. Insulin (Humulin, 28.6
      UI/day) was administered irrespective of diabetes occurrence to another group of
      rats for comparison. Blood glucose, insulin levels, glycosuria, degree of islet
      infiltration, and the expression of some antigens were observed. Results showed
      that the vitamin D(3) analog reduced diabetes incidence, although limitedly, in
      BB rats while administration of oral insulin increased diabetes incidence. In
      addition, the vitamin D(3) analog did not stimulate an enhancement in the
      expression of CD4 and CD25 in BB rats as it does in NOD mice, which may explain
      the failure of this as well as other antidiabetic treatments in the BB animal
      model of type 1 diabetes.

PMID- 16960874
TI  - Upregulations of Gata4 and oxytocin receptor are important in cardiomyocyte
      differentiation processes of P19CL6 cells.
AB  - Oxytocin induces P19 cells to differentiate into cardiomyocytes possibly through
      the oxytocin/oxytocin receptor system. We added oxytocin to the growth medium of
      P19CL6, a subline of P19, but they did not differentiate into cardiomyocytes as
      indicated by RT-PCR and Western blotting results. During the cardiac commitment
      time of P19CL6 cells, the mRNA expression levels of the oxytocin receptor were
      upregulated by the addition of oxytocin as well as DMSO, but an upregulation of
      Gata4 expression levels was only observed for the cells induced by DMSO. The in
      silico analysis of the upstream sequence of the oxytocin receptor predicted
      putative binding sites for Gata4 and Nkx2.5. These results suggest that
      upregulations of the oxytocin receptor and Gata4 are important for cardiomyocyte
      differentiation processes.

PMID- 16960875
TI  - Expression profiling of vitamin D treated primary human keratinocytes.
AB  - Vitamin D has attracted much attention by its ability to stop cell proliferation
      and induce differentiation, which became of particular interest for the treatment
      of cancer and psoriasis. We performed an expression profile of 12 hours and 24
      hours 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) treated primary
      human keratinocytes, to determine the changes in gene expression induced by the
      steroid in order to improve our understanding of the biological activity of
      1alpha,25(OH)(2)D(3). This we expect to be useful for establishing a test system
      for vitamin D analogs or might open new therapeutic targets or uses for the
      hormone. For the filter array experiments a non-redundant set of 2135 sequence
      verified EST clones was used. The normalized raw data of 2 filters per time point
      were combined and subjected to SAM analysis to further increase the statistical
      significance. 86 positive and 50 negative genes were identified after 12 h. The
      numbers went down to 43 positive and 1 negative gene after 24 h of treatment.
      Fifteen genes are up-regulated over a longer period of time (12 h and 24 h).
      Results were verified by real-time PCR and/or Northern blots. Targets identified
      are involved in intracellular signaling, transcription, cell cycle, metabolism,
      cellular growth, constitution of the extracellular matrix or the cytoskeleton and
      apoptosis, immune responses, and DNA repair, respectively. Expression profiles
      showed an initial stop of proliferation and induction of differentiation, and
      resumed proliferation after prolonged incubation, most likely due to degradation
      of the hormone.

PMID- 16960876
TI  - Nucleo-cytoplasmic cycling of the vitamin D receptor in the enterocyte-like cell
      line, Caco-2.
AB  - We examined the effects of 1,25 dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) on the
      distribution and mobility of the vitamin D receptor (VDR) in the enterocyte-like
      Caco-2 cell. Confocal microscopy showed that a green fluorescent protein-vitamin
      D receptor (GFP-VDR) fusion protein is predominantly nuclear (58%) and it does
      not associate with the apical or basolateral membrane of proliferating or
      polarized, differentiated cells. In contrast to the previously studied cell
      types, neither endogenous VDR nor GFP-VDR levels accumulate in the nucleus
      following 1,25(OH)(2)D(3) treatment (100 nM, 30 min). However, in nuclear
      photobleaching experiments nuclear GFP-VDR import was significantly increased by
      1,25(OH)(2)D(3) during both an early (0-5 min) and later (30-35 min) period (20%
      per 5 min). Compared to the natural ligand, nuclear import of GFP-VDR was 60%
      lower in cells treated with the 1,25(OH)(2)D(3) analog, 1-alpha-fluoro-16-ene-20
      epi-23-ene-26,27-bishomo-25-hydroxyvitamin D(3) (Ro-26-9228, 5 min, 100 nM).
      Downstream events like ligand-induced association of VDR with chromatin at 1 h
      and the accumulation of CYP24 mRNA were significantly lower in Ro-26-9228 treated
      cells compared to 1,25(OH)(2)D(3) (60 and 95% lower, respectively). Collectively
      our data are consistent with a role for ligand-induced nuclear VDR import in
      receptor activation. In addition, ligand-dependent VDR nuclear import appears to
      be balanced by export, thus accounting for the lack of nuclear VDR accumulation
      even when VDR import is significantly elevated.

PMID- 16960877
TI  - In vitro and in vivo differentiation of human umbilical cord derived stem cells
      into endothelial cells.
AB  - The successful use of tissue-engineered transplants is hampered by the need for
      vascularization. Recent advances have made possible the using of stem cells as
      cell sources for therapeutic angiogenesis, including the vascularization of
      engineered tissue grafts. The goal of this study was to examine the endothelial
      potential of human umbilical cord-derived stem (UCDS) cells. UCDS cells were
      initially characterized and differentiated in an endothelial differentiation
      medium containing VEGF and bFGF. Differentiation into endothelial cells was
      determined by acetylated low-density lipoprotein incorporation and expression of
      endothelial-specific proteins, such as PECAM and CD34. In vivo, the transplanted
      UCDS cells were sprouting from local injection and differentiated into
      endothelial cells in a hindlimb ischemia mouse model. These findings indicate the
      presence of a cell population within the human umbilical cord that exhibits
      characteristics of endothelial progenitor cells. Therefore, human umbilical cord
      might represent a source of stem cells useful for therapeutic angiogenesis and re
      endothelialization of engineered tissue grafts.

PMID- 16960878
TI  - Genetic network and pathway analysis of differentially expressed proteins during
      critical cellular events in fracture repair.
AB  - Bone repair consists of inflammation, intramembranous ossification,
      chondrogenesis, endochondral ossification, and remodeling. To better understand
      the translational regulation of these distinct but interrelated cellular events,
      we used the second generation of BD Clontechtrade mark Antibody Microarray to
      dissect and functionally characterize proteins differentially expressed between
      intact and fractured rat femur at each of these cellular events. Genetic network
      analysis showed that proteins differentially expressed within a given cellular
      event tend to be physically or functionally correlated. Seventeen such
      interacting networks were established over five cellular events that were most
      frequently associated with cell cycle, cell death, cell-to-cell signaling and
      interaction, and cell growth and proliferation. Eighteen molecular pathways were
      significantly enriched during the bone repair process, of which ERK/MAPK, NF-kB,
      PDGF, and T-cell receptor signaling pathways were significant during three or
      more cellular events. The analyses revealed dynamic temporal expression patterns
      and cellular-event-specific functions. The inflammation event on Day 1 was
      characteristic of the cell cycle-related molecular changes. The relative quiet
      stage of intramembranous ossification on Day 4 and the molecularly most active
      stage of chondrogenesis on Day 7 were featured by coordinated cell death and cell
      proliferation signals. Endochondral ossification on Day 14 experienced a clear
      transition from the molecular/cellular function to the physiological system
      development/function. The osteoclast-mediated remodeling on Day 28 was
      highlighted by the integrin signaling pathway. The distinct changes in protein
      expression during these cellular events provide a molecular basis for developing
      cellular event-targeted therapeutic strategy to accelerate bone healing.

PMID- 16960879
TI  - Immediate early gene IEX-1 induces astrocytic differentiation of U87-MG human
      glioma cells.
AB  - The immediate early response gene IEX-1 is involved in the regulation of
      apoptosis and cell growth. In order to increase the apoptotic sensitivity to
      chemotherapeutic drugs and gamma-ray, we attempted to establish U87-MG human
      glioma cell line expressing IEX-1. Unexpectedly, however, transfection of IEX-1
      into U87-MG glioma cells resulted in morphological changes to astrocytic
      phenotype and increase in glial differentiation marker proteins, S-100 and glial
      fibrillary acidic protein (GFAP). Glial cell differentiation was used to examine
      in rat C6 glioma cell line, since this cell line express astrocytic phenotypes by
      increase in intracellular cAMP concentration. Stimulation of human U87-MG glioma
      cells by membrane-permeable dibutyryl cAMP (dbcAMP) not only elicited their
      morphological changes but also induced expression of IEX-1 as well as S-100 and
      GFAP. H89, an inhibitor of protein kinase A (PKA), blocked dbcAMP-induced
      morphological changes of U87-MG cells and expression of IEX-1. In contrast,
      morphological changes and expression of S-100 and GFAP induced by IEX-1 were not
      affected by H89. Morphological changes induced by dbcAMP were totally abolished
      by functional disruption of IEX-1 expression by anti-sense RNA. These results
      indicate that IEX-1 plays an important role in astrocytic differentiation of
      human glioma cells and that IEX-1 functions at downstream of PKA.

PMID- 16960880
TI  - Lower extremity arterial thrombosis following sonographically guided thrombin
      injection of a femoral pseudoaneurysm.
AB  - Sonographically guided percutaneous thrombin injection is a minimally invasive
      and highly successful treatment of arterial pseudoaneurysms. Despite a very low
      complication rate, several severe arterial thrombotic events have been reported
      following thrombin injection of pseudoaneurysms. Native arterial thrombosis,
      though recognized as a severe complication of thrombin injection, has not been
      well described in the literature. We report a case of successful surgical
      management of arterial thrombosis after percutaneous thrombin injection of a
      femoral artery pseudoaneurysm in a 69-year-old woman. The pathophysiology, risk
      factors, diagnosis, and treatment options for this complication are discussed.

PMID- 16960881
TI  - Tardus-parvus Doppler waveform in the renal arteries of an adult patient
      suggesting aortic coarctation.
AB  - A 19-year-old man presented with arterial hypertension without blood pressure
      difference between his upper and lower extremities. Duplex Doppler sonography was
      performed to rule out renal artery stenosis and revealed a tardus-parvus pattern
      in both renal arteries as well as in the abdominal aorta, whereas the left
      subclavian artery showed a normal waveform, suggesting a more distal obstruction.
      Aortography confirmed a severe aortic coarctation. Because the typical signs and
      symptoms of aortic coarctation may not be present, especially in adults, a tardus
      parvus pattern in the abdominal aorta and its branches, contrasting with a normal
      pattern in the supra-aortic arteries, should suggest the diagnosis.

PMID- 16960882
TI  - First trimester screening aids in the diagnosis and management of an ectopic
      pregnancy in a noncommunicating uterine horn.
AB  - Pregnancy within a noncommunicating rudimentary horn has a 70% chance of
      rupturing, with a maternal mortality of 0.5%. It is most commonly managed with
      operative removal of the horn. We report a pregnancy within a noncommunicating
      horn and highlight the advantage of early diagnosis via sonography. First
      trimester prenatal screening via sonographic examination allows early diagnosis
      of mullerian duct abnormalities and ectopic pregnancy. This information expedites
      management of such pregnancies, thus decreasing maternal morbidity and increasing
      the chance of future fertility.

PMID- 16960883
TI  - Sonographic appearance of a testicular yolk sac tumor in a 2-year-old boy.
AB  - Yolk sac tumor (YST) of testis is the most common of all childhood testicular
      malignancies. We report a case of testicular YST in a 2-year-old boy. The tumor
      appeared sonographically as an ovoid, homogeneous, well-circumscribed, isoechoic,
      solid testicular mass with good sound-through transmission and increased internal
      vascularity on color Doppler imaging. The serum alpha-fetoprotein level was 4,396
      ng/ml. Pathological examination confirmed YST at at stage I. Although the
      sonographic appearance of YST of the testis is nonspecific, the diagnosis is
      achievable in clinical practice on the combination of elevated serum alpha
      fetoprotein level and sonograms depicting a solid testicular hypervascular mass.

PMID- 16960884
TI  - Torsion of a giant omental cyst mimicking ascites.
AB  - We report a case of omental cyst in an 11-month-old infant. The cyst occupied
      nearly the whole abdomen and mimicked massive ascites on sonography. The correct
      preoperative diagnosis was achieved through the use of CT, and partial torsion of
      a huge omental cyst was found at surgery. The diagnostic role of sonography and
      CT in ascites of unknown etiology is emphasized.

PMID- 16960885
TI  - Caveolin-1 polarization in migrating endothelial cells is directed by substrate
      topology not chemoattractant gradient.
AB  - Polarization is a hallmark of migrating cells, and an asymmetric distribution of
      proteins is essential to the migration process. Caveolin-1 is highly polarized in
      migrating endothelial cells (EC). Several studies have shown caveolin-1
      accumulation in the front of migrating EC while others report its accumulation in
      the EC rear. In this paper we address these conflicting results on polarized
      localization of caveolin-1. We find evidence for the hypothesis that different
      modes of locomotion lead to differences in protein polarization. In particular,
      we show that caveolin-1 is primarily localized in the rear of cells migrating on
      a planar substrate, but in the front of cells traversing a three-dimensional
      pore. We also show that a chemoattractant, present either as a gradient or
      ubiquitously in the medium, does not alter caveolin-1 localization in cells in
      either mode of locomotion. Thus we conclude that substrate topology, and not the
      presence of a chemoattractant, directs the polarization of caveolin-1 in motile
      ECs.

PMID- 16960886
TI  - Tau interacts with Golgi membranes and mediates their association with
      microtubules.
AB  - Tau, a microtubule-associated protein enriched in the axon, is known to stabilize
      and promote the formation of microtubules during axonal outgrowth. Several
      studies have reported that tau was associated with membranes. In the present
      study, we further characterized the interaction of tau with membranous elements
      by examining its distribution in subfractions enriched in either Golgi or
      endoplasmic reticulum membranes isolated from rat brain. A subfraction enriched
      with markers of the medial Golgi compartment, MG160 and mannosidase II, presented
      a high tau content indicating that tau was associated with these membranes.
      Electron microscope morphometry confirmed the enrichment of this subfraction with
      Golgi membranes. Double-immunogold labeling experiments conducted on this
      subfraction showed the direct association of tau with vesicles labeled with
      either an antibody directed against MG160 or TGN38. The association of tau with
      the Golgi membranes was further confirmed by immunoisolating Golgi membranes with
      an anti-tau antibody. Immunogold labeling confirmed the presence of tau on the
      Golgi membranes in neurons in vivo. Overexpression of human tau in primary
      hippocampal neurons induced the formation of large Golgi vesicles that were found
      in close vicinity to tau-containing microtubules. This suggested that tau could
      serve as a link between Golgi membranes and microtubules. Such role for tau was
      demonstrated in an in vitro reconstitution assay. Finally, our results showed
      that some tau isoforms present in the Golgi subfraction were phosphorylated at
      the sites recognized by the phosphorylation-dependent antibodies PHF-1 and AT-8.

PMID- 16960887
TI  - Evaluation of a participatory ergonomic intervention aimed at improving
      musculoskeletal health.
AB  - BACKGROUND: Participatory ergonomic (PE) interventions have been increasingly
      utilized to deal with work-related musculoskeletal disorders (WMSD). METHODS:
      Using a longitudinal quasi-experimental design, a PE process was launched at one
      depot of a large courier company, with a nearby depot serving as a control.
      Evaluations focused on 122 employees across the two depots who participated in
      both pre- and post-questionnaires. An evaluation framework assessed the process
      of implementation, changes in risk factors, and changes in musculoskeletal health
      outcomes. Partial and multiple regressions explored the relationships in the
      evaluation framework. RESULTS: Changes in work organizational factors had a
      consistent impact upon changes in health outcomes. Greater participation in the
      process was associated with increased levels of job influence and communication
      (P = 0.0059 and P = 0.0940 respectively). Improvements in communication levels
      were associated with reduced pain intensity and improved work role function (WRF)
      (P = 0.0077 and P = 0.0248 respectively). Lower levels of pain post-intervention
      were related to greater WRF (P = 0.0493). CONCLUSIONS: A PE approach can improve
      risk factors related to WMSD, and meaningful worker participation in the process
      is an important aspect for the success of such interventions.

PMID- 16960888
TI  - Continued exposure to silica after diagnosis of silicosis in Brazilian gold
      miners.
AB  - BACKGROUND: There is a paucity of studies analyzing the effect of continued
      silica exposure after the onset of silicosis with regard to disease progression.
      The present study investigates differences in clinical and radiological
      presentation of silicosis among former workers with a diagnosis of silicosis, and
      compares workers who continued to be exposed to silica with those who stopped
      silica exposure after having received their diagnosis. METHODS: A sample of 83
      former gold miners with a median of 21 years from the first diagnoses of
      silicosis, had their clinical and occupational histories taken and underwent both
      chest radiography (International Labor Organization standards) and spirometry.
      Their silica exposure was assessed and an exposure index was created. The main
      outcome was the radiological severity of silicosis and tuberculosis (TB). The
      statistical analysis was done by multiple logistic regression. RESULTS: Among the
      83 miners, 44 had continued exposed to silica after being diagnosed with
      silicosis. Continuation of silica exposure was associated with advanced
      radiological images of silicosis (X-ray classification in category 3, OR = 6.42,
      95% CI = 1.20-34.27), presence of coalescence and/or large opacities (OR = 3.85,
      CI = 1.07-13.93), and TB (OR = 4.61, 95% CI = 1.14-18.71). CONCLUSIONS:
      Differential survival is unlikely to explain observed differences in silicosis
      progression. Results reinforce the recommendation that silica exposure should be
      halted at an early stage whenever X-ray is suggestive of the disease.

PMID- 16960889
TI  - Cognitive impairment and olfactory panic from occupational exposure to VOCs.
AB  - BACKGROUND: A Canadian government clerical worker in her early thirties developed
      frontal lobe dysfunction from inhalation of volatile organic compounds off-gassed
      during an office renovation. METHODS: Pulmonary function, bronchial provocation,
      allergy testing, and a brain (SPECT) scan were performed. RESULTS: SPECT scanning
      showed frontotemporal hypoperfusion and neuropsychologic testing revealed
      deficits in verbal learning and poor organizational memory. CONCLUSIONS: A
      significant component of this worker's impairment was the development of
      "olfactory panic," a debilitating aversion to odor accompanied by symptoms of
      panic. The Ontario Workplace Safety and Insurance Appeals Tribunal granted
      entitlement for her cognitive difficulties and olfactory panic as a result of her
      toxic exposure.

PMID- 16960890
TI  - Long-term effects of tumor necrosis factor-alpha treatment on insulin signaling
      pathway in HepG2 cells and HepG2 cells overexpressing constitutively active
      Akt/PKB.
AB  - Tumor necrosis factor-alpha (TNF-alpha) mediated attenuation of insulin signaling
      pathway is an important cause in several disorders like obesity, obesity linked
      diabetes mellitus. TNF-alpha actions vary depending upon concentration and time
      of exposure in various cells. In the present study, the effects of long-term TNF
      alpha (1 ng/ml) exposure on the components of insulin signaling pathway in HepG2
      and HepG2 cells overexpressing constitutively active Akt1/PKB-alpha (HepG2-CA
      Akt/PKB) have been investigated. In parental HepG2 cells, TNF-alpha treatment for
      24 h reduced the phosphorylation of Akt1/PKB-alpha and GSK-3beta and under these
      conditions cells also showed reduced insulin responsiveness in terms of Akt1/PKB
      alpha and GSK-3beta phosphorylation. TNF-alpha pre-incubated HepG2-CA-Akt/PKB
      cells showed lower reduction in Akt1/PKB-alpha and GSK-3beta phosphorylation and
      insulin responsiveness after 24 h as compared to parental HepG2 cells. We report
      that the long-term TNF-alpha pre-incubation in both parental HepG2 and HepG2-CA
      Akt/PKB-alpha cells leads to the reduction in the levels of IRS-1 without
      altering the levels of IRS-2. In order to understand the reason for the
      differential insulin resistance in both the cell types, the effect of long-term
      TNF-alpha treatment on the proteins upstream to Akt/PKB was investigated. TNF
      alpha pre-incubation also showed reduced insulin-stimulated Tyr phosphorylation
      of insulin receptor (IR-beta) in both the cell types, moreover
      hyperphosphorylation of IRS-1 at Ser 312 residue was observed in TNF-alpha pre
      incubated cells. As hyperphosphorylation of IRS-1 at Ser 312 can induce its
      degradation, it is possible that reduced insulin responsiveness after long-term
      TNF-alpha pre-incubation observed in this study is due to the decrease in IRS-1
      levels.

PMID- 16960891
TI  - Actin filaments are involved in the maintenance of Golgi cisternae morphology and
      intra-Golgi pH.
AB  - Here we examine the contribution of actin dynamics to the architecture and pH of
      the Golgi complex. To this end, we have used toxins that depolymerize
      (cytochalasin D, latrunculin B, mycalolide B, and Clostridium botulinum C2 toxin)
      or stabilize (jasplakinolide) filamentous actin. When various clonal cell lines
      were examined by epifluorescence microscopy, all of these actin toxins induced
      compaction of the Golgi complex. However, ultrastructural analysis by
      transmission electron microscopy and electron tomography/three-dimensional
      modelling of the Golgi complex showed that F-actin depolymerization first induces
      perforation/fragmentation and severe swelling of Golgi cisternae, which leads to
      a completely disorganized structure. In contrast, F-actin stabilization results
      only in cisternae perforation/fragmentation. Concomitantly to actin
      depolymerization-induced cisternae swelling and disorganization, the intra-Golgi
      pH significantly increased. Similar ultrastructural and Golgi pH alkalinization
      were observed in cells treated with the vacuolar H+ -ATPases inhibitors
      bafilomycin A1 and concanamycin A. Overall, these results suggest that actin
      filaments are implicated in the preservation of the flattened shape of Golgi
      cisternae. This maintenance seems to be mediated by the regulation of the state
      of F-actin assembly on the Golgi pH homeostasis.

PMID- 16960892
TI  - Automated maintenance of embryonic stem cell cultures.
AB  - Embryonic stem cell (ESC) technology provides attractive perspectives for
      generating unlimited numbers of somatic cells for disease modeling and compound
      screening. A key prerequisite for these industrial applications are standardized
      and automated systems suitable for stem cell processing. Here we demonstrate that
      mouse and human ESC propagated by automated culture maintain their mean specific
      growth rates, their capacity for multi-germlayer differentiation, and the
      expression of the pluripotency-associated markers SSEA-1/Oct-4 and Tra-1-60/Tra-1
      81/Oct-4, respectively. The feasibility of ESC culture automation may greatly
      facilitate the use of this versatile cell source for a variety of biomedical
      applications.

PMID- 16960893
TI  - Effect of free ammonia and free nitrous acid concentration on the anabolic and
      catabolic processes of an enriched Nitrosomonas culture.
AB  - The effects of free ammonia (FA; NH(3)) and free nitrous acid (FNA; HNO(2))
      concentrations on the metabolisms of an enriched ammonia oxidizing bacteria (AOB)
      culture were investigated using a method allowing the decoupling of growth and
      energy generation processes. A lab-scale sequencing batch reactor (SBR) was
      operated for the enrichment of an AOB culture. Fluorescent in-situ hybridization
      (FISH) analysis showed that 82% of the bacterial population in the SBR bound to
      the NEU probe specifically designed for Nitrosomonas europaea. Batch tests were
      carried out to measure the oxygen and ammonium consumption rates by the culture
      at various FA and FNA levels, in the presence or absence of inorganic carbon
      (CO(2), HCO(3) (-), and CO(3) (2-)). It was revealed that FA of up to 16.0
      mgNH(3)-N . L(-1), which was the highest concentration used in this study, did
      not have any inhibitory effect on either the catabolic or anabolic processes of
      the Nitrosomonas culture. In contrast, FNA inhibited both the growth and energy
      production capabilities of the Nitrosomonas culture. The inhibition on growth
      initiated at approximately 0.10 mgHNO(2)-N . L(-1), and the data suggested that
      the biosynthesis was completely stopped at an FNA concentration of 0.40 mgHNO(2)
      N . L(-1). The inhibition on energy generation initiated at a slightly lower
      level but the Nitrosomonas culture was still oxidizing ammonia at half of the
      maximum rate at an FNA concentration of 0.50-0.63 mgHNO(2)-N . L(-1). The
      affinity constant of the Nitrosomonas culture with respect to ammonia was
      determined to be 0.36 mgNH(3)-N . L(-1), independent of the presence or absence
      of inorganic carbon.

PMID- 16960895
TI  - A simplified technique for evaluating the adherence of yeasts to human vaginal
      epithelial cells.
AB  - Thousands of women all over the world annually suffer of vulvovaginal candidiasis
      (VVC), an infection caused by yeasts, which mainly affect the mucosa of the vulva
      and vagina. The adherence of the yeasts to the mucosae is an essential step for
      colonization and predisposes the start of the infectious process. In this study,
      a technique capable of evaluating the adhesion of yeasts to human vaginal
      epithelial cells (HVEC) was employed. Twenty-five vaginal yeast isolates (10
      Candida albicans, nine C. glabrata, two C. parapsilosis, one C. tropicalis, two
      Saccharomyces cerevisiae, and one Trichosporon sp.) were evaluated. A suspension
      of each yeast was co-incubated with HVEC obtained from a healthy donor in the
      ovulatory phase. After 1 hr, smears were made, stained with crystal violet and
      Papanicolaou, and the number of yeasts that adhered to 600 HVEC was evaluated.
      The adhesion of C. albicans was significantly greater than that of the other
      species and occurred mainly in the intermediate HVEC, rather than the
      superficial. In addition, the proposed technique, easy to execute and of low cost
      showed to be reproducible and enables the determination of the adherence capacity
      of different isolates, whose adhesion was confirmed by scanning electron
      microscopy.

PMID- 16960894
TI  - Low specificity of anti-tissue transglutaminase antibodies in patients with
      primary biliary cirrhosis.
AB  - The association between celiac disease (CD) and primary biliary cirrhosis (PBC)
      is well documented in medical literature; however, a high frequency of false
      positive results of the anti-transglutaminase (anti-tTG) test has been reported
      in patients with PBC. To verify if the positive results for anti-tTG autoantibody
      are false positives due to cross reactivity with mitochondrial antigens, we
      studied 105 adult patients affected with PBC, positive for anti-mitochondrial M2
      antibodies. Anti-tTG IgA antibodies were studied by using six different
      immunoenzymatic assays that employ the tTG antigen obtained from different
      sources (human recombinant, placenta, red blood cells, and guinea pig liver). On
      the whole, 28 out of 105 PBC subjects tested positive for anti-tTG IgA
      antibodies, but only two were eventually found to be affected by CD; the other 26
      were shown to be false positive. The specificity of the various antigenic
      substrates ranged from 88.5% of the human erythrocytes tTG to 97.1% of the human
      recombinant tTG. The results of this study showed that a true association between
      PBC and CD was present in only 2% of the patients and that, in most cases, the
      false positive results were attributable to the type of substrate utilized in the
      assay.

PMID- 16960896
TI  - Reference distributions for apolipoproteins AI and B and the apolipoprotein B/AI
      ratios: a practical and clinically relevant approach in a large cohort.
AB  - The two serum apolipoproteins in the highest concentrations, apolipoprotein (apo)
      AI and apolipoprotein B, and the apolipoprotein B/AI ratio are measured to assess
      clinical risk for atherosclerotic heart and peripheral vascular diseases. The
      study is based on a cohort of over 37,000 Caucasian individuals from northern New
      England measured in one laboratory by immunonephelometry using standardized
      reference materials. All samples received for protein analyses were accepted
      provided adequate identifying information was available. Laboratory and
      demographic information was entered into a single database for subsequent study.
      Our results show that for males without evidence of inflammation, values of apo
      AI change little through life. For females, however, values gradually increase
      until about 60 years of age then fall somewhat thereafter. Among adults, females
      have higher apo AI values on average, than males. Apo B values change
      significantly through life, increasing after the end of the second decade to a
      peak during the sixth decade, then falling thereafter. In the past, concern has
      been expressed that apo AI is an acute phase reactant (APR), thus complicating
      cardiovascular risk assessment. The effects of an APR (C-reactive protein >or=10
      mg/L) on apo AI, but not on apo B, are measurable for both sexes, most noticeably
      beyond the age of 60 years in males and females. When values were expressed as
      age- and gender-specific multiples of the median (MoMs), the resulting
      distributions fit a log-Gaussian distribution well over a broad range. The size
      of the relatively homogenous cohort, by a standardized approach, provides a firm
      basis for comparison to preexisting reference intervals and for establishing a
      clinically useful and current reference interval for the three main
      apolipoprotein values.

PMID- 16960897
TI  - Prevalence of antiphospholipid antibodies in Chilean patients with rheumatoid
      arthritis.
AB  - Antiphospholipid (aPL) antibodies found in patients with autoimmune diseases are
      also detected in those with inflammatory diseases. The purpose of this study was
      to examine the prevalence of these antibodies in patients with rheumatoid
      arthritis (RA), and to evaluate the association of these antibodies with
      thrombosis and/or other clinical characteristics of this inflammatory disorder.
      Eighty-four patients with RA and 82 normal controls were studied. Anticardiolipin
      (aCL), anti-beta(2) glycoprotein I (anti-beta(2)GPI), and antiprothrombin (aPT)
      antibodies and the lupus anticoagulant (LA) activity were determined. Seven out
      of 84 (8.3%) patients were positive for aCL, six out of 84 (7.2%) for anti
      beta(2)GPI, and six out of 84 (7.2%) for aPT, while in controls the overall
      prevalence of aPL antibodies was 3.6% (3 out of 82). All patients and controls
      were LA negative. There was no correlation between the presence of aPL with
      thrombosis and/or other clinical features of the antiphospholipid syndrome. We
      found aPL antibodies in 19.1% (16 out of 84) of the patients with rheumatoid
      arthritis and this prevalence was statistically higher than in normal controls
      (P<0.003). In this study, the presence of aPL antibodies was not associated with
      the development of thrombosis and/or thrombocytopenia. Whether the presence of
      aPL antibodies implies an increased risk for thrombosis and atherosclerosis in
      these patients should be studied further.

PMID- 16960898
TI  - A new enzyme-linked chemiluminescent immunosorbent digoxin assay is virtually
      free from interference of spironolactone, potassium canrenoate, and their common
      metabolite canrenone.
AB  - Spironolactone and potassium canrenoate (aldosterone antagonist diuretics) are
      sometimes used in conjunction with digoxin for patient management.
      Spironolactone, potassium canrenoate, and their common metabolite canrenone
      interfere with serum digoxin measurement using various immunoassays. Recently a
      new enzyme-linked chemiluminescent immunosorbent digoxin assay (ECLIA-Digoxin)
      became commercially available for application on the ADVIA IMS 800i modular
      system (Bayer HealthCare, Tarrytown, NY). We investigated the potential
      interference of spironolactone and related compounds in this assay by comparing
      the results with the fluorescence polarization immunoassay (FPIA), which is known
      to have significant cross-reactivity with these compounds as well as a
      turbidimetric assay for digoxin with no known cross-reactivity with
      spironolactone and related compounds. Aliquots of drug free serum were
      supplemented with therapeutic and above therapeutic concentrations of
      spironolactone, canrenone, and potassium canrenoate, and apparent digoxin
      concentrations were measured. No apparent digoxin concentration was observed
      using the ECLIA-Digoxin or turbidimetric assay. When serum pools prepared from
      patients receiving digoxin were further supplemented with these compounds, we
      observed no significant change in digoxin concentrations in the presence of these
      compounds with the ECLIA-Digoxin. We conclude that this assay is virtually free
      from interferences from spironolactone, potassium canrenoate and their common
      metabolite canrenone.

PMID- 16960899
TI  - Reference distributions for apolipoproteins AI and B and B/AI ratios: comparison
      of a large cohort to the world's literature.
AB  - Limiting the clinical utility of apolipoproteins AI (apo AI) and B (apo B) and
      the apo B/AI ratios until the last decade has been the lack of satisfactory
      methods for quantifying serum levels and credible reference materials. Great
      technological strides have been made in the last few years. The remaining barrier
      to more relevant and cost-effective use of serum protein data for diagnosis and
      prognosis has been the availability of widely recognized reliable reference
      intervals from birth to old age for both males and females. A total of 82
      publications reporting reference intervals have been identified that meet most of
      the same inclusion criteria used in our prior six studies. These have been
      analyzed statistically and compared to similar studies, i.e., sufficient number,
      listed subject criteria, method, and reference material, in general terms.
      Published smaller studies with constrained age ranges, agree on average with our
      large series of life-long reference intervals that range from less than one year
      to over 80 years. This study was performed to assess the degree of agreement
      between smaller reference interval studies to our large population analysis. This
      meta-analysis provides support and reassurance that many of the smaller reference
      intervals published previously fall within reasonable limits of out large
      population.

PMID- 16960900
TI  - Enterovirus meningitis in Greece from 2003-2005: diagnosis, CSF laboratory
      findings, and clinical manifestations.
AB  - Enteroviruses (EVs) are the most commonly identified cause of aseptic meningitis.
      Rapid detection and characterization of EV meningitis is essential in making
      decisions for patient management and treatment. A total of 52 cases of acute
      aseptic meningitis that occurred from March 2003 to April 2005 were investigated
      for EVs using viral culture and/or molecular methods directly in the
      cerebrospinal fluid (CSF). EVs were detected in 21 out of 52 (40.4%) patients
      using reverse transcription-PCR (RT-PCR) and/or tissue culture. EVs were isolated
      from six out of 37 (16.2%) cultured specimens, while 20 out of 52 (38.4%)
      specimens yielded positive results when 5'non-coding region (5'NCR) RT-PCR assay
      was used. One specimen that was culture-positive was RT-PCR-negative. Using the
      VP1-2A RT-PCR and sequence analysis, 14 of the 21 positive EVs were identified
      as: four strains of Coxsackie virus B5, five echovirus 11, two echovirus 9, one
      echovirus 5, one echovirus 14, and one Coxsackie virus A9. Fever, headache,
      vomiting, and stiff neck were the most pronounced symptoms. Pleocytosis with the
      predominance of lymphocytes and mild elevated protein levels characterized the
      CSF specimens. Coxsackie virus B5 and echovirus 11 were the predominant serotypes
      during the study period. Although there was seasonal enteroviral activity (April
      November), cases also occurred in the cold months. The 5'NCR and VP1-2A RT-PCR
      with sequence analysis were found to be superior to conventional methods for
      direct diagnosis and the typing of EVs.

PMID- 16960901
TI  - Analysis of TIMP-1 gene polymorphisms in Italian sclerodermic patients.
AB  - Systemic sclerosis (SSc) is an autoimmune disease characterized by skin and
      internal organs fibrosis due to an extracellular matrix (ECM) accumulation of
      type I collagen. The turnover of the ECM is dependent on the balance between
      matrix metalloproteinases (MMPs) and tissue inhibitors of matrix
      metalloproteinases (TIMPs). The disruption of this balance is involved in SSc
      because higher serum TIMP-1 levels have been demonstrated in SSc patients than in
      controls. On this basis, we analyzed three polymorphisms: -19A>G, +261C>T, and
      +372T>C of the TIMP-1 gene in SSc patients (67 females, eight males) and controls
      (29 females, nine males). The C allele of the +372T>C single nucleotide
      polymorphism (SNP) was observed at a higher frequency in male patients than in
      healthy individuals (P=0.02), while no differences were observed in the female
      subjects. Our findings suggest that the +372T>C polymorphism of the TIMP-1 gene
      is associated with SSc in male individuals. No association with the clinical
      characteristics of SSc Italian patients and TIMP-1 gene polymorphisms was
      observed. Thus, the role of TIMP-1 gene in predisposition to SSc remains
      controversial.

PMID- 16960902
TI  - Hydrogen-bonded oligo(p-phenylenevinylene) functionalized with perylene bisimide:
      self-assembly and energy transfer.
AB  - We describe the synthesis, supramolecular ordering on surfaces and in solution,
      and photophysical characterization of OPV4UT-PERY, an oligo(p-phenylenevinylene)
      (OPV) with a covalently attached perylene bisimide moiety. In chloroform, the
      molecule forms dimers through quadruple hydrogen bonding of the ureido-s-triazine
      array. This is supported by scanning tunneling microscopy (STM) studies, which
      reveal dimer formation at the liquid (1,2,4-trichlorobenzene)/solid (graphite)
      interface. Moreover, contrast reversal in bias-dependent STM imaging provides
      information on the ordering and different electronic properties of the oligo(p
      phenylenevinylene) and perylene bisimide moieties. In dodecane, the molecule self
      assembles into H-type aggregates that are still soluble as a result of the
      hydrophobic shell formed by the dodecyloxy wedges. The donor-acceptor molecule is
      characterized by efficient energy transfer from the photoexcited OPV to the
      perylene bisimide. Mixed assemblies with analogous OPVs lacking the perylene
      bisimide unit have been prepared in dodecane solution and energy transfer to the
      incorporated perylene bisimides has been studied by fluorescence spectroscopy.

PMID- 16960903
TI  - Water-soluble ionic liquids as novel stabilizers in suspension polymerization
      reactions: engineering polymer beads.
AB  - Aqueous solutions of ionic liquids have been used as novel and environmentally
      friendly reaction media to synthesize and "control" the size of different cross
      linked polymer beads by suspension polymerization reactions. It was found that
      the investigated ionic liquids can act as novel stabilizing agents of the
      suspensions as a result of their surface-active properties. The results have
      demonstrated that the average size of polymer beads can be varied from the macro-
      to the nanoscale and their surface area can also be "adjusted" by this synthetic
      approach. Furthermore, the use of a combination of ionic liquids and water for
      the synthesis of polymers, the simple isolation of the products formed in this
      polymerization procedure, as well as the recycling of the continuous medium for
      further reactions open up possibilities for the development of "new and green"
      polymerization processes.

PMID- 16960904
TI  - Investigation of reactivity and selectivity of DNA-alkylating duocarmycin
      analogues by high-resolution mass spectrometry.

PMID- 16960905
TI  - Antitumor agents: development of highly potent glycosidic duocarmycin analogues
      for selective cancer therapy.

PMID- 16960906
TI  - Iron and manganese corroles are potent catalysts for the decomposition of
      peroxynitrite.

PMID- 16960908
TI  - Intramolecular orbital alignment observed in the photodissociation of
      [D1]thiophenol.

PMID- 16960907
TI  - Glycomimetic cyclic peptides stimulate neurite outgrowth.

PMID- 16960909
TI  - Total synthesis of azumamides A and E.

PMID- 16960910
TI  - Molecular mapping of the recognition interface between the islet amyloid
      polypeptide and insulin.

PMID- 16960911
TI  - On water and in air: fast and highly chemoselective transfer hydrogenation of
      aldehydes with iridium catalysts.

PMID- 16960912
TI  - A luminescent poly(phenylenevinylene)-amylose composite with supramolecular
      liquid crystallinity.

PMID- 16960913
TI  - Oxygen-deficiency-induced superlattice structures of chromia nanobelts.

PMID- 16960914
TI  - Molecular recognition: preorganization of a bis(pyrrole) Schiff base derivative
      for tight dimerization by hydrogen bonding.
AB  - Multiple techniques have been used to delineate the self-assembly of a
      bis(pyrrole) Schiff base derivative (compound 4, C(16)H(14)N(4)), which forms an
      unusual dimer through complementary N-H...N=C hydrogen bonds between twisted, C2
      symmetric monomer units. The asymmetric unit of the crystal structure comprises
      one and a half dimer units, with one dimer exhibiting approximate D2 point-group
      symmetry and the other exact D2 symmetry (space group C2/c). The dimers pack into
      columns whose axes are collinear with the a axis of the unit cell. The columns
      assemble into discrete layers with two distinct types of hydrogen-sized voids
      residing between the layers. Despite the promising architecture of the voids
      within the lattice of 4, the absence of genuine channels to interconnect the
      voids precludes the uptake of hydrogen gas, even at elevated pressures (10 bar).
      AM1 calculations of the structure of dimeric 4 indicate that self-recognition
      through hydrogen bonding depends primarily on favorable electrostatic
      interactions. The potential-energy surface for monomeric 4 mapped by counter
      rotation of an adjacent pair of C=C-N=C torsion angles indicates that the X-ray
      structures of the four monomeric units are global minima with highly nonplanar
      conformations that are preorganized for self-recognition by hydrogen bonding. The
      in vacuo enthalpy of association for the dimer was calculated to be significantly
      exergonic (DeltaG(assoc)=-21.9 kJ mol(-1), 298 K) and in excellent agreement with
      that determined by 1H NMR spectroscopy in CDCl3 (DeltaG(assoc)=-16.6(4) kJ mol(
      1), 298 K). Using population and bond order analyses, in conjunction with the
      conformation dependence of the frontier MO energies, we have been able to show
      that pi-electron delocalization is only marginally diminished in the nonplanar
      conformers of 4 and that the electronic structures of the constituent monomers of
      the dimer are well mixed.

PMID- 16960915
TI  - Adenoviral vector platform for transduction of constitutive and regulated
      tricistronic or triple-transcript transgene expression in mammalian cells and
      microtissues.
AB  - BACKGROUND: Adenoviral particles can efficiently transduce a broad spectrum of
      cell types, so they are widely used in basic research and clinical trials.
      METHODS: We have developed a novel adenoviral vector platform for delivery of
      constitutive or streptogramin-inducible expression of up to three therapeutic
      transgenes into a variety of murine and human cell lines, primary cells and
      microtissues. RESULTS: Coordinated expression of three independent transgenes in
      a compact genetic format was achieved by two different expression configurations:
      (i) The multicistronic expression format consisting of a single constitutive
      (simian virus 40 promoter, P(SV40); murine or human cytomegalovirus immediate
      early promoter, P(mCMV), P(hCMV)) or regulated (streptogramin-inducible)
      promoters (P(PIR)ON2) driving the expression of a single multicistronic
      transcript of which the first cistron is translated in a cap-dependent manner and
      the two subsequent ones by internal ribosome entry site (IRES)-mediated
      translation initiation. (ii) The triple-transcript expression configuration, in
      which a combination of well-established (P(SV40), P(hCMV), P(mCMV)) and novel
      synthetic constitutive promoters (P(GTX)) control transcription of three
      expression units. The constitutive multigene expression design enabled
      coordinated high-level expression of the Bacillus stearothermophilus-derived
      secreted alpha-amylase (SAMY), the human vascular endothelial growth factor 121
      (VEGF(121)) and the human placental secreted alkaline phosphatase (SEAP) in
      monolayer populations and microtissues of Chinese hamster ovary cells (CHO-K1),
      human fibrosarcoma cells (HT-1080), primary neonatal rat cardiomyocytes (NRCs)
      and primary human aortic fibroblasts (HAFs). Streptogramin-inducible tricistronic
      SAMY-VEGF(121)-SEAP expression provided excellent regulation performance-high
      level induction in the presence of the streptogramin antibiotic pristinamycin I
      (PI), near-undetectable basal expression in the absence of PI, optimal
      adjustability and perfect reversibility-in all cell types, in particular in NRCs
      and NRC-derived myocardial microtissues. CONCLUSIONS: Triple-transcript and
      tricistronic expression configurations conserve the DNA packaging capacity of the
      size-constrained viral transduction systems and enable coordinated and regulated
      expression of up to three therapeutic transgenes for concerted clinical
      interventions in future gene therapy scenarios.

PMID- 16960916
TI  - Lentiviral vector integration sites in human NOD/SCID repopulating cells.
AB  - BACKGROUND: Recent observations of insertional mutagenesis in preclinical and
      clinical settings emphasize the relevance of investigating comprehensively the
      spectrum of integration sites targeted by specific vectors. METHODS: We followed
      the engraftment of lentivirally transduced human cord blood (CB) progenitor cells
      after transplantation into NOD/SCID mice using a self-inactivating HIV-1-derived
      vector expressing the enhanced green fluorescent protein (EGFP). RESULTS: The
      mean of transduction of CD34(+) CB cells was 41%, as deduced from the percentage
      of EGFP(+) cells before transplantation. At 3 weeks post-transplantation, the
      average of EGFP(+) cells in the human cell population was 65 +/- 8%, and
      increased to 75 +/- 10% at 12 weeks post-transplantation. In order to determine
      the proviral integration sites in human NOD/SCID repopulating cells (SRCs) we
      used the ligation-mediated polymerase chain reaction (LM-PCR) technique. Sixty
      eight percent of the integrations were found to be located in RefSeq genes, most
      of them in intron regions. Twenty percent of these integrations occurred within a
      distance of 10 kb from the transcription start site; a percentage that is
      significantly lower compared to that observed in cells transduced by
      gammaretroviral vectors. Sixty-two percent of integrations occurred in genes with
      a biological function in cell metabolism, and four integrations were located in
      genes with a role in tumorigenesis. CONCLUSIONS: These investigations indicate
      that integration of lentiviral vectors in human repopulating cells capable of
      engrafting NOD/SCID mice preferentially occur in coding regions of the human
      genome. Nevertheless, the clustering of integrations at the transcriptional start
      is not as high as that observed for gammaretroviral vectors.

PMID- 16960917
TI  - Common infections in diabetes: pathogenesis, management and relationship to
      glycaemic control.
AB  - Specific defects in innate and adaptive immune function have been identified in
      diabetic patients in a range of in vitro studies. However, the relevance of these
      findings to the integrated response to infection in vivo remains unclear,
      especially in patients with good glycaemic control. Vaccine efficacy seems
      adequate in most diabetic patients, but those with type 1 diabetes and high
      glycosylated haemoglobin levels are most likely to exhibit hypo-responsiveness.
      While particular infections are closely associated with diabetes, this is usually
      in the context of extreme metabolic disturbances such as ketoacidosis. The link
      between glycaemic control and the risk of common community-acquired infections is
      less well established but could be clarified if infection data from large
      community-based observational or intervention studies were available. The
      relationship between hospital-acquired infections and diabetes is well
      recognized, particularly among post-operative cardiac and critically ill surgical
      patients in whom intensive insulin therapy improves clinical outcome independent
      of glycaemia. Nevertheless, further research is needed to improve our
      understanding of the role of diabetes and glycaemic control in the pathogenesis
      and management of community- and hospital-acquired infections.

PMID- 16960918
TI  - Confinement effects on electromigration of long DNA molecules in an ordered
      cavity array.
AB  - Confinement effects on the electromigration of long dsDNA molecules in an array
      of well-ordered, molecular sized cavities interconnected by nanopores are
      described. The array was prepared by replicating the structure of a colloidal
      crystal of microspheres in a polymer matrix. Both conformation and mobility
      studies show that the electrophoretic behavior of large DNA molecules is distinct
      from that in gels and other microfabricated sieves, showing a peak in mobility
      versus electric field, and an inversion in the separation order with field
      strength. A simple model was proposed to interpret this unexpected observation
      qualitatively. We conclude that the molecular behavior of DNA can be modified by
      the combination of entropic effect and electric trapping as a consequence of both
      unique geometry and conductivity of this cavity array material. This approach
      provides insights for design and optimization of on-chip molecular sieving
      structures for rapid separation of long DNA molecules. It may lead to a promising
      material for manipulation and size fractionation of other biological
      macromolecules.

PMID- 16960919
TI  - Analysing multicentre competing risks data with a mixed proportional hazards
      model for the subdistribution.
AB  - In the competing-risks setting, to test the effect of a covariate on the
      probability of one particular cause of failure, the Fine and Gray model for the
      subdistribution hazard can be used. However, sometimes, competing risks data
      cannot be considered as independent because of a clustered design, for instance
      in registry cohorts or multicentre clinical trials. Frailty models have been
      shown useful to analyse such clustered data in a classical survival setting,
      where only one risk acts on the population. Inclusion of random effects in the
      subdistribution hazard has not been assessed yet. In this work, we propose a
      frailty model for the subdistribution hazard. This allows first to assess the
      heterogeneity across clusters, then to incorporate such an effect when testing
      the effect of a covariate of interest. Based on simulation study, the effect of
      the presence of heterogeneity on testing for covariate effects was studied.
      Finally, the model was illustrated on a data set from a registry cohort of
      patients with acute myeloid leukaemia who underwent bone marrow transplantation.

PMID- 16960920
TI  - Candidate early predictors for progression to joint damage in systemic juvenile
      idiopathic arthritis.
AB  - OBJECTIVE: To assess if joint damage at 2 years after diagnosis in patients with
      systemic juvenile idiopathic arthritis (SJIA) can be predicted by clinical or
      laboratory features assessed up to 3 or 6 months after diagnosis. METHODS:
      Medical records from 70 children were retrospectively reviewed. The primary
      outcome measure was presence of joint damage at 2 years after diagnosis (JD2) as
      defined by presence of erosions or fusion in one or more joints. Potential
      predictor variables for JD2 in the first 3 and 6 months after diagnosis consisted
      of the highest observed white blood cell count, platelet count, erythrocyte
      sedimentation rate, active joint count, and presence of symptomatic pulmonary or
      cardiac disease or macrophage activation syndrome, and treatment data. RESULTS:
      The outcome of interest, JD2, was identified in 15/70 patients. Classification
      tree analysis identified a pair of variables (highest observed platelet count and
      number of active joints) measured within the first 3 months after diagnosis that
      together predicted progression to JD2 with an estimated sensitivity of 87%,
      specificity of 82%, and positive predictive value of 57%. Multivariate logistic
      regression analyses at 3 months found that higher quantities of joints with
      active arthritis and early use of methotrexate (MTX) were factors significantly
      associated with increased odds of progression to JD2 (active joints odds ratio =
      1.08, 95% CI 1.00-1.16, p = 0.04; MTX OR = 11.85, 95% CI 1.89-74.26, p = 0.01).
      Unsupervised cluster analysis identified 2 major phenotypes of patients at 3
      months characterized by different ages at onset, acute phase markers, active
      joint counts, and presence of serositis. These phenotypes differed 3-fold in
      proportion of subjects progressing to JD2 (p < 0.05). CONCLUSION: By 3 months
      after diagnosis, a clinical phenotype based on active joint count and platelet
      count may be prognostic of an increased risk of progression to JD2. Use of
      corticosteroids did not appear to change the risk of joint damage. In contrast,
      the presence of serositis appeared to be associated with decreased risk of joint
      damage.

PMID- 16960921
TI  - The Symptom Intensity Scale, fibromyalgia, and the meaning of fibromyalgia-like
      symptoms.
AB  - OBJECTIVE: To characterize a scale for the measurement of fibromyalgia (FM)-like
      symptoms; to investigate whether FM is a discrete disorder; to understand the
      significance of FM-like symptoms; and to investigate causal and noncausal factors
      in the development of such symptoms. METHODS: We evaluated 25,417 patients with
      rheumatic disease using the Symptom Intensity (SI) Scale, a self-report scale
      that combines a count of pain in 19 nonarticular regions with a visual analog
      scale for fatigue. We studied this scale in relation to demographics, clinical
      symptoms, and serious outcomes, including serious medical illnesses,
      hospitalization, work disability, and death. RESULTS: Compared with other
      rheumatic disease assessments, the SI scale was the best identifier of symptoms
      associated with FM content, including an increase in general medical symptoms. SI
      scale elevations were associated with increases in cardiovascular disorders,
      hospitalization, work disability, and death. Persons with socioeconomic
      disadvantage by reason of sex, ethnicity, household income, marital status,
      smoking, and body mass had increased SI scores. For almost all clinical variables
      studied, the prevalence and/or severity of the variable increased linearly with
      SI scores. CONCLUSION: We identified a clinical marker for general symptom
      intensification that applies in all patients and is independent of a diagnosis of
      FM. We found no clinical basis by which FM may be identified as a separate
      entity. Higher scores on the SI scale were associated with more severe medical
      illness, greater mortality, and sociodemographic disadvantage, and these factors
      appear to play a role in the development of FM-like symptoms and symptom
      intensification.

PMID- 16960922
TI  - Increasing incidence of Wegener's granulomatosis in Sweden, 1975-2001.
AB  - OBJECTIVE: Studies of Wegener's granulomatosis (WG) since the late 1980s indicate
      a probable increase in incidence of unknown cause and significance, possibly
      related to antineutrophil cytoplasmic antibody (ANCA) testing. To extend these
      observations and to include calendar periods before ANCA was introduced, we
      assessed time trends in the incidence of WG in Sweden in the period 1975-2001.
      METHODS: In the population-based Swedish Inpatient Register, we identified 1938
      individuals diagnosed with WG in the period 1975-2001, and calculated the annual
      age and sex adjusted incidences. RESULTS: The incidence increased from 0.33 (95%
      CI 0.28-0.39) in the period 1975-85 to 0.77 (95% CI 0.69-0.85) in 1986-90, to
      1.19 (95% CI 1.12-1.26) in 1991-2001, resulting in a mean incidence of 0.78 (95%
      CI 0.74-0.82). CONCLUSION: WG displays a strong temporal trend. While the
      increase coincides to some extent with the implementation of ANCA testing,
      suggestive of increased disease recognition, ANCA testing remains an incomplete
      explanation as increasing incidences were noted before as well as after their
      introduction.

PMID- 16960923
TI  - Effect of infliximab therapy on employment, time lost from work, and productivity
      in patients with psoriatic arthritis.
AB  - OBJECTIVE: To examine the effect of infliximab on employment status, time lost
      from work, and productivity in a double-blind, placebo-controlled study of
      patients with active psoriatic arthritis (PsA). METHODS: Two hundred adult
      patients with PsA were randomized to intravenous infusions of either infliximab 5
      mg/kg or placebo at Weeks 0, 2, 6, 14, and 22, with early escape at Week 16.
      Employment status, workdays missed, and productivity were assessed at baseline
      and at Week 14. The effect of PsA on daily productivity was assessed using a
      visual analog scale. RESULTS: At baseline, similar percentages of patients in
      both treatment groups were employed and similar percentages missed workdays; the
      mean productivity score at baseline was similar between groups (roughly 3 on a
      scale of 0 to 10). At Week 14, median productivity increased significantly in the
      infliximab group compared with the placebo group (67.5% vs 9.2%; p < 0.0001).
      Compared with the placebo group, higher proportions of patients in the infliximab
      group improved employment status from unemployed at baseline to employed at Week
      14 (11.5% vs 0%; p = 0.084) and from part-time to full-time employment (30.0% vs
      10.0%; p = 0.582). Among patients employed at baseline and Week 14, a lower
      proportion of patients in the infliximab group than in the placebo group had
      missed workdays in the 4 weeks prior to Week 14 (p = 0.138). CONCLUSION: After 14
      weeks of treatment, infliximab improved productivity in patients with active PsA.
      There was also a trend toward increased employment and reduced time lost from
      work for patients treated with infliximab.

PMID- 16960924
TI  - Membrane glucocorticoid receptor expression on peripheral blood mononuclear cells
      in patients with ankylosing spondylitis.
AB  - OBJECTIVE: To investigate the expression of membrane glucocorticoid receptors
      (mGCR) on peripheral blood mononuclear cells (PBMC) in patients with ankylosing
      spondylitis (AS). METHODS: We used high sensitivity immunofluorescence with
      magnetofluorescent liposomes for the detection of mGCR on PBMC from patients with
      AS (n = 26) and healthy controls (n = 11). RESULTS: The frequency of mGCR+
      monocytes and B lymphocytes was significantly higher in patients with AS than in
      controls (monocytes 12.5 +/- 9.9% vs 4.8 +/- 1.4%, B lymphocytes 8.7 +/- 6.3% vs
      4.4 +/- 3.6%). We did not find mGCR on T lymphocytes. The frequency of mGCR+
      cells did not correlate with variables of AS disease activity [C-reactive
      protein, erythrocyte sedimentation rate, Bath Ankylosing Spondylitis Disease
      Activity Index (BASDAI), BASDAI 6, or numerical rating scales]. CONCLUSION: mGCR
      are upregulated in monocytes and B lymphocytes of patients with AS. This
      upregulation does not correlate with the humoral or overall disease activity.
      mGCR are not present on T lymphocytes. Our findings may be related to the limited
      benefit of low-dose and the efficacy of high-dose (intravenous pulse or
      intraarticular) glucocorticoid treatment in AS. Drugs binding selectively to mGCR
      may be a new therapeutic option for AS.

PMID- 16960925
TI  - Posterior reversible encephalopathy syndrome--an underrecognized manifestation of
      systemic lupus erythematosus.
AB  - OBJECTIVE: Posterior reversible encephalopathy syndrome (PRES) is a rare,
      recently described neurologic condition identifiable by clinical presentation and
      magnetic resonance image (MRI) appearance. It is associated with renal
      insufficiency, hypertension, and rheumatologic diseases. Patients present with
      headache, seizures, loss of vision and altered mental function, and a pattern on
      imaging studies of predominantly transient, posterior cerebral hyperintensities
      on T2-weighted MRI. There is a high likelihood of presentation of this syndrome
      to a rheumatologist. METHODS: Three recent cases of systemic lupus erythematosus
      (SLE) with PRES, along with 9 previously reported cases, are reviewed. RESULTS:
      All 3 patients presented with seizures and subacute visual changes in association
      with lupus nephritis. The first presented with hypertension, complete visual
      field loss, and status epilepticus 2 weeks after starting oral cyclosporine
      therapy for refractory lupus nephritis. The second patient was normotensive and
      presented with seizures and visual symptoms while in hospital with SLE-related
      pancreatitis and nephritis. The third patient had headache and seizures with
      severe lupus disease activity including nephritis, pancytopenia, and pulmonary
      hemorrhage. Cranial MRI showed predominantly posterior signal abnormalities on T2
      weighted images, which resolved after cessation of cyclosporine in the first
      case, treatment with IV cyclophosphamide in the second case, and treatment with
      cyclophosphamide and plasmapheresis in the final case. Literature review showed
      that PRES is a manifestation of SLE or a consequence of therapy with calcineurin
      inhibitors or rituximab. The hallmark features are visual loss and seizures.
      Severe hypertension (> 170/110 mm Hg) and renal failure were present in the
      majority of previously identified cases of SLE and PRES. Our second case was
      normotensive but had marked lupus disease activity. PRES can lead to cerebral
      infarction. CONCLUSION: With increasing availability of MRI, PRES will be
      identified more frequently. Swift action to identify potential offending agents,
      controlling hypertension, and treating active disease can lead to reversal of
      radiologic and neurologic findings.

PMID- 16960926
TI  - Association between dental caries and pneumonia in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To establish the association between oral pathology and pneumonia in
      patients with systemic lupus erythematosus (SLE). METHODS: Thirty women with SLE,
      consecutively admitted for hospitalization because of pneumonia, and 60
      noninfected controls with SLE (30 hospitalized and 30 ambulatory), matched by
      age, sex, and date of hospitalization to the cases, were enrolled. At entry,
      information about sociodemographic variables, traditional infection risk factors,
      SLE characteristics, treatment, and comorbidity was gathered by medical chart
      review. In every patient, one rheumatologist performed a complete physical
      examination, and assessed disease activity and chronic damage using validated
      indices; and one periodontist performed a standardized oral health evaluation
      including the use of 6 international oral health indices. RESULTS: Twenty-eight
      patients with community-acquired and 2 patients with nosocomial pneumonias were
      included. Age of the total study population was 38.8 +/- 14.6 years, mean number
      of SLE criteria 6.3 +/-1.95, and disease duration 6.6 +/- 7.2 years, with no
      differences among the 3 groups. Cases had greater disease activity and damage,
      and were taking higher doses of prednisone than ambulatory controls (p <or=
      0.03). Cases accrued more traditional infection risk factors than ambulatory
      controls and had lower levels of serum albumin than both control groups (p <or=
      0.04). Oral health was worse among the cases, including more periapical lesions,
      cervical and third-grade caries, and a higher mean number of caries/patient than
      controls (p <or= 0.05). In the multivariate analysis, third-grade caries (odds
      ratio 7.5, 95% CI 2.05-27.3, p = 0.002) was strongly associated with pneumonia.
      CONCLUSION: Poor oral hygiene and third-grade caries are common in patients with
      SLE who develop pneumonia.

PMID- 16960927
TI  - Can severity be predicted by treatment variables in rheumatoid arthritis
      administrative data bases?
AB  - OBJECTIVE: Administrative data bases provide rapid access to data regarding
      treatment and morbidity of rheumatoid arthritis (RA). A serious limitation of
      administrative data bases is the lack of information regarding RA severity, as in
      the case of lymphoma, where RA severity may contribute to the cause of the
      adverse outcome. We examined whether treatment variables could predict RA
      severity. METHODS: We studied 7541 patients with RA who were participating in a
      longitudinal study of RA outcomes. Disease severity was determined by the Patient
      Activity Scale (PAS), which represents on a 0 to 10 scale the mean of 0-10
      standardized values of pain (by visual analog scale), patient global severity,
      and the Health Assessment Questionnaire. We tested the ability of disease
      modifying antirheumatic drugs (DMARD) and biologic treatment variables and the
      lifetime number of these treatments to predict severity status. The receiver
      operating characteristic (ROC) area under the curve (AUC) was used to describe
      the association between severity and treatment variables. RESULTS: There was
      little difference in PAS scores between various treatments and treatment groups,
      including scores of the 18.3% of patients receiving no DMARD or biologic therapy.
      The ROC AUC to distinguish PAS scores above and below the median was 0.64 (60.5%
      correctly classified) and was 0.70 (67.2% correctly classified) in distinguishing
      first compared to fourth quartiles PAS scores. CONCLUSION: Treatment variables do
      not accurately or usefully identify severity status. As a corollary, there is
      little difference in severity between patients receiving different treatment
      regimens, and actual measures of severity rather than treatment surrogates are
      required to assess RA severity.

PMID- 16960928
TI  - Sleep disturbance in patients with rheumatoid arthritis: evaluation by medical
      outcomes study and visual analog sleep scales.
AB  - OBJECTIVE: Except for some polysomnography studies, there have been no large
      quantitative studies of sleep disturbance (SD) in rheumatoid arthritis (RA). SD
      has taken on new importance with the observation that etanercept and infliximab
      reduce daytime sleepiness, and patient groups indicate that sleep is an important
      issue. METHODS: We evaluated 8676 patients with RA and a comparison group of 1364
      subjects with non-fibromyalgia, noninflammatory disorders (NID) using the Medical
      Outcome Study (MOS) sleep questionnaire, including 2 MOS sleep problem indexes
      (SPI-I, SPI-II) and the MOS SD scale. In addition, patients completed a visual
      analog scale (VAS) sleep disturbance scale (SDS). RESULTS: The scales had similar
      mean values: SPI-I 35.4 (19.4), SPI-II 36.0 (19.1), SDS 35.0 (24.7), and VAS
      sleep 36.1 (29.7), and the values for the MOS scales exceeded population norms by
      25% (VAS by 42%). In multivariable analyses SD was primarily determined by pain
      and mood. Patients receiving anti-tumor necrosis factor (TNF) did not have less
      abnormal sleep scores. SD was comparable in RA and NID. The VAS scale was more
      strongly associated with RA clinical variables than the MOS scales; however, the
      distributional characteristics of the scales differed, with the VAS scales
      capturing more extreme values. The standard error of the measurement (SEM), which
      is related to minimal (important) change, was SPI-I 9.0, SPI-II 7.3, SDS 9.6, and
      VAS sleep 10.4. CONCLUSION: SD is increased in RA, and 25% to 42% of SD can be
      attributed to RA. SD is linked to pain, mood, and disease activity. SD is
      slightly greater in women and is less with increasing age. All scales appear to
      be valid in RA, with minimal differences in SEM.

PMID- 16960929
TI  - Value of the HLA-DRB1 shared epitope for predicting radiographic damage in
      rheumatoid arthritis depends on the individual patient risk profile.
AB  - OBJECTIVE: To investigate the influence of individual patient risk profiles on
      the value of the HLA-DRB1 shared epitope (SE) as a predictor of severe erosive
      damage in rheumatoid arthritis (RA). METHODS: Patient characteristics, clinical
      signs and symptoms, rheumatoid factor (RF) status, and HLA-DRB1 genotypes were
      available for 154 Caucasian women with RA. Risk profiles were defined by non
      genetic factors that predict severe erosive disease. The additional value of the
      SE was defined by the likelihood ratios (LR) of SE presence and absence, which
      were calculated at the individual patient level. RESULTS: In the total
      population, the LR of SE presence was 1.42 and the LR of SE absence was 0.37,
      corresponding to an odds ratio of 3.9, indicating a substantially higher risk of
      severe erosive disease in those with the SE compared to those without. The LR of
      SE presence and absence varied depending on the risk profile of the women, from
      1.01 to 2.25 for SE presence and 0.22 to 0.49 for SE absence. Considering all the
      patient characteristics, SE status was most significantly related to RF status.
      Consequently, the LR of SE presence and absence were higher for RF-negative women
      compared to RF-positive women (SE presence 1.77 vs 1.40, p < 0.001 and SE absence
      0.38 vs 0.30, p < 0.001). CONCLUSION: The additional value of SE testing for
      predicting severe erosive disease varies according to patient risk profiles.
      Given the likely availability of genetic and other novel tests in the future,
      information about the additional value of test results is needed to ensure the
      optimal use of such testing in the management of RA.

PMID- 16960931
TI  - Lupus and thrombosis.

PMID- 16960930
TI  - Comparison of tacrolimus and mizoribine in a randomized, double-blind controlled
      study in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To compare the efficacy and safety of tacrolimus and mizoribine in
      patients with rheumatoid arthritis (RA). METHODS: Adult patients with RA with an
      insufficient response to at least one disease modifying antirheumatic drug
      (DMARD) were randomized to receive 28 weeks of double-blind treatment with
      tacrolimus 3 mg once daily or mizoribine 50 mg three times daily. The primary
      efficacy endpoint was the American College of Rheumatology 20% (ACR20) response.
      Safety was evaluated by adverse events. RESULTS: A total of 204 patients were
      enrolled for study (103 in the tacrolimus group, 101 in the mizoribine group).
      Significantly more patients receiving tacrolimus achieved an ACR20 response
      compared with mizoribine (48.5 vs 10.0%, respectively; p = 0.001). Tacrolimus was
      also superior to mizoribine in ACR50 and ACR70 response rate, tender and painful
      joint counts, swollen joint counts and patient and physician assessments of pain,
      disease activity, and patient's physical function assessment based on the
      Modified Health Assessment Questionnaire (p < 0.001). Adverse events were more
      frequent in the tacrolimus group than the mizoribine group (65.0 vs 59.4%);
      however, there were no statistically significant differences between treatment
      groups. CONCLUSION: Tacrolimus improves RA symptoms to a significantly greater
      extent than mizoribine in patients with RA inadequately controlled with at least
      one prior DMARD. Tacrolimus has the potential to be a useful and highly effective
      treatment for RA.

PMID- 16960932
TI  - Depression and employment among people with arthritis.

PMID- 16960934
TI  - Dyspnea due to pulmonary hypertension and interstitial lung disease in
      scleroderma: room for improvement in diagnosis and management.

PMID- 16960933
TI  - Arthritis, continuing medical education, and oil sand: changes in market forces
      can alter perceptions of an underutilized resource.

PMID- 16960935
TI  - Intranasal administration of recombinant human cartilage glycoprotein-39. A phase
      I escalating cohort study in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate safety and tolerability and pilot efficacy of repeated
      single doses of Org39141 in patients with active rheumatoid arthritis (RA). Org
      39141 is recombinant human cartilage glycoprotein-39, intended to induce mucosal
      tolerance upon intranasal administration. METHODS: RA patients with moderate
      disease activity were treated for 4 weeks and followed for another 8 weeks. The
      trial had a sequential cohort design: RA patients in the first cohort received 4
      intranasal doses (one per week) of either 25 microg Org 39141 or placebo; in
      subsequent cohorts, treatment with 125microg, 625 microg, or 3125 microg Org39141
      was compared to placebo. Safety was evaluated by means of reporting adverse
      events, standard laboratory testing, and nose examination. The primary efficacy
      endpoint was RA disease activity as measured by the Disease Activity Score 28
      (DAS28). RESULTS: A total of 36 patients were randomized. Org39141 was well
      tolerated, and no severe or serious adverse events (AE) were reported. In the
      pooled placebo group, a decrease in DAS28 was observed, but to a lesser extent
      than in the Org 39141 treatment groups. After 4 weeks of treatment, the mean
      decrease in DAS in the 625 microg Org 39141 treatment group (-24%) was
      statistically (p = 0.02) and clinically (EULAR criteria) significantly larger
      than in the pooled placebo group (-3%). Once-weekly intranasal treatment with
      Org39141 was well tolerated, and no serious or severe AE were reported. A trend
      towards efficacy was observed. Our results are encouraging for further clinical
      development of Org39141.

PMID- 16960936
TI  - Insufficient endogenous control of tumor necrosis factor-alpha contributes to
      temporomandibular joint pain and tissue destruction in rheumatoid arthritis.
AB  - OBJECTIVE: To investigate whether pain and tissue destruction in the
      temporomandibular joint (TMJ) of patients with rheumatoid arthritis (RA) are
      influenced by plasma levels of the proinflammatory cytokine tumor necrosis factor
      alpha (TNF-alpha) or the soluble receptor TNFsRII. METHODS: Fifty-one patients
      with RA were included. TMJ resting pain intensity, pain intensity upon mandibular
      movement, tenderness to palpation, pressure-pain threshold, and presence of
      anterior open bite were assessed. Venous blood was obtained for analysis of TNF
      alpha, TNFsRII, and inflammatory markers. RESULTS: A total of 29 patients had TMJ
      pain and 22 patients had anterior open bite. In the group of patients with TMJ
      pain, 12 had anterior open bite and 17 did not. In the patients without TMJ pain
      10 patients had anterior open bite and 12 did not. Patients with or without
      anterior open bite did not differ regarding any investigated variable. Plasma TNF
      alpha and TNFsRII were positively correlated in the total patient sample. TNFsRII
      was negatively correlated with degree of anterior open bite in patients with TMJ
      pain but positively correlated with TMJ pressure-pain threshold in patients with
      elevated plasma TNF-alpha. CONCLUSION: Our results indicate that insufficient
      systemic endogenous control of TNF-alpha seems to contribute to TMJ pain and
      tissue destruction in RA.

PMID- 16960937
TI  - Plasma level of CXC-chemokine CXCL12 is increased in rheumatoid arthritis and is
      independent of disease activity and methotrexate treatment.
AB  - OBJECTIVE: Several actions of the chemokine CXCL12 have potential relevance for
      rheumatoid arthritis (RA). Interaction with CXCR4, the unique receptor for
      CXCL12, stimulates angiogenesis, mononuclear cell trafficking into the joints,
      lymphoid-tissue-like rearrangement of T cells within the synovium, and
      chondrocyte release of cartilage-degrading metalloproteinases. We investigated
      the level of CXCL12 in plasma (p-CXCL12) as a marker of RA diagnosis, RA disease
      activity, and response to methotrexate (MTX) treatment. METHODS: A prospective
      study including 36 patients with RA (ACR criteria) of at least 6 months'
      duration, and 50 sex and age matched healthy controls. ELISA for CXCL12 was
      performed on plasma prior to and after 16 and 28 weeks of MTX treatment in the
      patients with RA and once in controls. RESULTS: The p-CXCL12 was 1855 +/- 145
      pg/ml in RA patients and 1273 +/- 79 pg/ml in controls (p < 0.001). During the 28
      weeks of MTX treatment, the ACR disease activity variables decreased, whereas the
      p-CXCL12 level remained constant and increased. P-CXCL12 was not correlated to
      any ACR disease activity variable at any time (p > 0.05). CONCLUSION: Patients
      with RA had a significantly and constantly increased p-CXCL12 level compared to
      controls. The p-CXCL12 level was independent of any ACR disease activity
      variables, as well as response to MTX treatment.

PMID- 16960938
TI  - Anti-beta2-glycoprotein I: prevalence, clinical correlations, and importance of
      persistent positivity in patients with antiphospholipid syndrome and systemic
      lupus erythematosus.
AB  - OBJECTIVE: Antibodies to beta2-glycoprotein I (anti-beta2-GPI) are found in a
      large percentage of patients with primary or secondary antiphospholipid syndrome
      (APS). Our aim was to identify the prevalence and clinical correlation of these
      antibodies in patients with APS and systemic lupus erythematosus (SLE), in
      comparison to anticardiolipin (aCL) and the lupus anticoagulant (LAC). We
      investigated whether serial samples improve clinical utility. METHODS: Serum
      samples for anti-beta2-GPI (IgG, IgM, IgA), aCL (IgG, IgM, IgA), and LAC (by
      dilute Russell viper venom time; RVVT) were collected from 418 consecutive
      patients with SLE or APS between October 2002 and March 2003. Clinical and
      serologic data of these patients were analyzed. RESULTS: A total of 185 (44.5%)
      patients were positive for anti-beta2-GPI, 55.3% were positive for aCL, and 31.1%
      for LAC. Anti-beta2-GPI was more common in Caucasians than in African Americans
      (p = 0.098). IgM and IgA were the most frequent isotypes of anti-beta2-GPI. aCL
      and anti-beta2-GPI were highly associated (p < 0.0001 to p = 0.0177, depending on
      isotype). A positive association was found between the presence of the LAC by
      dilute RVVT and anti-beta2-GPI IgG (p < 0.0001), IgM (p < 0.0001), and IgA (p =
      0.0002) antibodies. Persistent positivity increased the association of venous and
      arterial thrombosis with anti-beta2-GPI (IgG and IgM isotypes). Pregnancy loss,
      seizures, and migraines were not associated with anti-beta2-GPI. IgA anti-beta2
      GPI was not significantly associated with any manifestation of APS. CONCLUSION:
      The prevalence of anti-beta2-GPI IgM and IgA was very high in our population.
      Measurement of anti-beta2-GPI IgG is clinically useful in identifying patients
      with SLE at higher risk for venous and arterial thrombosis. Persistent positivity
      increased the association of IgG anti-beta2-GPI with venous thrombosis and anti
      beta2-GPI IgM with arterial thrombosis. IgA anti-beta2-GPI was not significantly
      associated with APS manifestations.

PMID- 16960939
TI  - High resolution computed tomography in fibrosing alveolitis associated with
      systemic sclerosis.
AB  - OBJECTIVE: To investigate the use of high resolution computed tomography (HRCT)
      in diagnosis of patients with fibrosing alveolitis associated with systemic
      sclerosis (FA-SSc), and to determine predictors of disease progression. METHODS:
      We retrospectively studied 90 patients with SSc who had undergone an initial
      (Time 1) and followup (Time 2) clinical and HRCT evaluation, with a mean +/- SD
      interval of 5.14 +/- 2.98 years between T1 and T2. RESULTS: At T1, HRCT was
      normal in 40 patients; at T2, 34/40 (85%) continued to have a normal HRCT. For
      the 50 patients with FA-SSc on HRCT scan at T1, the overall disease progression
      comprised extension of lung changes toward the apices with worsening of lung
      fibrosis at T2. Among the 37 patients who had areas of isolated ground-glass
      opacities at T1, 25 (68%) had progression of lung fibrosis at T2. These 25
      patients were mostly men, who showed a more marked decrease of diffusing capacity
      and a longer interval between T1 and T2. CONCLUSION: The results emphasize the
      good longterm prognosis indicated by a normal initial HRCT in SSc. Patients with
      FA-SSc with abnormal HRCT experienced progressive replacement of ground-glass
      opacities by honeycombing and/or traction bronchiectasis/bronchiolectasis. Ground
      glass opacity is probably the first step of lung fibrosis in SSc, and treatment
      should be discussed even at this early stage.

PMID- 16960940
TI  - Use of etanercept in the treatment of dermatomyositis: a case series.
AB  - OBJECTIVE: To evaluate the efficacy of etanercept, a recombinant human soluble
      fusion protein of tumor necrosis factor-alpha (TNF-alpha) type II receptor and
      IgG1, in patients with adult dermatomyositis (DM). METHODS: Five patients with
      active DM were studied. All patients reported muscle weakness and had elevated
      muscle enzymes creatine kinase and lactate dehydrogenase. Because of lack of
      response to steroid and cytotoxic therapy, etanercept was given at a dose of 25
      mg subcutaneously twice a week for at least 3 months. RESULTS: All patients
      experienced an exacerbation of disease, with increase of muscle weakness,
      elevation of muscle enzyme levels, and unchanged rash. Treatment with etanercept
      was stopped. After receiving a combination of methotrexate (MTX) and
      azathioprine, disease manifestations improved in all patients. CONCLUSIONS: In
      our case series, TNF-alpha inhibition by etanercept was not effective, suggesting
      that a broad immunosuppressive therapy is needed to treat DM.

PMID- 16960941
TI  - Celecoxib is efficacious and well tolerated in treating signs and symptoms of
      ankylosing spondylitis.
AB  - OBJECTIVE: To evaluate the efficacy and safety of celecoxib in patients with
      ankylosing spondylitis (AS). METHODS: This was a 12-week randomized, double
      blind, placebo-controlled study with 4 treatment arms: celecoxib 200 mg qd,
      celecoxib 400 mg qd, naproxen 500 mg bid, and placebo. Patients (age 18-75 yrs)
      requiring daily treatment with nonselective nonsteroidal antiinflammatory drugs,
      and with a pain intensity on visual analog scale (VAS) > or = 50 mm worsening by
      30% compared with a preinclusion visit (14 days prior) were studied. Primary
      endpoints were least-squares mean changes from baseline in pain intensity,
      disease activity (patient global assessment VAS), and functional impairment [Bath
      Ankylosing Spondylitis Functional Index (BASFI)]. Adverse events were monitored
      throughout the study. RESULTS: Of 611 randomized patients, 137 were allocated to
      celecoxib 200 mg, 161 to celecoxib 400 mg, 157 to naproxen, and 156 to placebo.
      Improvements in least-squares mean pain intensity, disease activity, and BASFI
      scores were significantly greater in the celecoxib 200 mg, celecoxib 400 mg, and
      naproxen groups than in the placebo group (p < or = 0.001) at Week 12 and the
      interim timepoints, Weeks 1, 3, and 6. Celecoxib 400 mg was as effective as
      naproxen; however, naproxen was more effective than celecoxib 200 mg. Celecoxib
      was well tolerated, with an adverse event profile similar to placebo. However, 3
      naproxen-treated patients experienced serious treatment-related gastrointestinal
      (GI) adverse events (one severe gastric ulcer, one moderate GI hemorrhage, one
      severe GI hemorrhage). CONCLUSION: In this 12-week study, celecoxib 200 mg qd and
      400 mg qd were efficacious and well tolerated in treating signs and symptoms of
      AS.

PMID- 16960942
TI  - Characteristics of chronic gout in Northern Sulawesi, Indonesia.
AB  - OBJECTIVE: To identify associations and possible risk factors for gout that may
      contribute to chronic tophaceous gout in rural and urban districts of North
      Sulawesi, Indonesia. METHODS: A total of 190 patients with chronic gout and 190
      age and sex matched controls were selected from 28 community health centers.
      Potential risk factors including alcohol consumption, food habits, family
      history, body weight, related medical conditions, drug use, and laboratory
      investigations were sought. RESULTS: Alcohol consumption and certain food habits
      were associated with gout. A positive family history of gout and overweight were
      also significant risk factors. Renal impairment was found in 86.3% of patients
      and hyperuricemia in 92.1%. In controls, renal impairment and hyperuricemia were
      7.4% and 32.6%, respectively. Patients with hypertension and nephrolithiasis were
      more at risk of having associated gout. There was a significant association
      between gout, hyperuricemia, hypercholesterolemia, hypertriglyceridemia, and
      higher levels of creatinine and urea. There was also a significantly lower level
      of urine uric acid in gout cases compared with controls. Gouty tophi were found
      in 91% of these cases with chronic gout. The use of diuretics for treating
      hypertension, continuing excessive alcohol consumption and purine-rich food
      habits in untreated gout, and hyperuricemia were associated with chronic and
      tophaceous gout. Urate-lowering drugs were not available in the community health
      centers. CONCLUSION: Severe tophaceous gout with deformities and disability is
      found in North Sulawesi. Prominent risk factors include alcohol, obesity, renal
      impairment, diet, hypertension, and family history. Improved education about gout
      seems needed. Urate-lowering drugs are not available in community health centers
      but are needed, especially in rural areas, as studied here.

PMID- 16960944
TI  - Longterm efficacy of topical nonsteroidal antiinflammatory drugs in knee
      osteoarthritis: metaanalysis of randomized placebo controlled clinical trials.
AB  - OBJECTIVE: To evaluate the longterm efficacy of topical therapies for pain
      control in primary knee osteoarthritis (OA). METHODS: Systematic literature
      search was carried out from January 1, 1966, to December 31, 2004, in Pubmed,
      Medline, Embase, and Cochrane database. Manual searches of related journals in
      the National Medical Library (New Delhi, India), the library of our institute,
      and conference abstracts were also carried out. We included randomized controlled
      clinical trials of 4 weeks or more comparing any topical nonsteroidal
      antiinflammatory drug (NSAID) with placebo or vehicle. Effect size for pain
      control was estimated. RESULTS: Out of 172 citations, 4 studies fulfilled all the
      specified criteria. Four of them compared topical NSAID with placebo or vehicle.
      Pooled effect of topical NSAID measured at 4 weeks or beyond was superior to
      placebo/vehicle in pain relief (mean effect size -0.28, 95% CI -0.42 to -0.14).
      CONCLUSION: Topical NSAID are effective for pain relief in knee OA for a longer
      duration; however, this may not hold true for all the preparations.

PMID- 16960943
TI  - Chondrocyte death induced by pathological concentration of chemokine stromal cell
      derived factor-1.
AB  - OBJECTIVE: It had been found that the concentration of chemokine stromal cell
      derived factor-1 (SDF-1) was significantly higher in synovial fluid (SF) of
      patients with osteoarthritis (OA; > or = 200 ng/ml) and rheumatoid arthritis (RA;
      > or = 700 ng/ml) compared to controls (< or = 100 ng/ml). Our aim was to
      determine whether the pathological concentration of SDF-1 induces chondrocyte
      death and to investigate mechanisms underlying such death. METHODS: Human OA
      chondrocytes were treated with different doses of SDF-1, or in combination with
      SF from patients with arthritis. Apoptotic and necrotic cells were labeled by
      annexin V and propidium iodide, respectively, and quantified by FACS analysis.
      Caspase-3 activity was quantified by a plate absorbance assay, and matrix
      metalloproteinase 13 mRNA levels were determined by RT-PCR. The release of high
      mobility group box chromatin protein 1, a specific marker of cell necrosis, and
      the activities of chondrocyte mitogen-activated protein kinases (MAPK) including
      ERK, JNK, and p38 in response to SDF-1 treatment were quantified by Western blot
      analysis. RESULTS: Pathological concentrations of SDF-1 (> or = 200 ng/ml) in SF
      or in recombinant form induced death of human chondrocytes in a necrosis
      dependent manner. Chondrocyte death was inhibited by the treatment of cells with
      anti-CXCR4, an antibody blocking the interaction between SDF-1 and its receptor
      CXCR4. However, the rate of chondrocyte apoptosis and the level of caspase-3, a
      key apoptotic enzyme, were not affected by the treatment with anti-CXCR4. SDF-1
      stimulated p38 MAPK activity in a dose- and time-dependent manner. The presence
      of the p38 MAPK inhibitor SB203580 during SDF-1 treatment abolished the induction
      of chondrocyte death by SDF-1. CONCLUSION: Our findings suggest a novel
      pathological mechanism by which high concentrations of SDF-1 in SF induce
      chondrocyte death during OA and RA.

PMID- 16960945
TI  - The relationship between the knee adduction moment and knee pain in middle-aged
      women without radiographic osteoarthritis.
AB  - OBJECTIVE: . An abnormally high knee adduction moment increases the medial
      tibiofemoral compartment load at the knee during gait, and is an important
      biomechanical marker of joint pathology. This cross-sectional study examines the
      relationship between the knee adduction moment and knee pain in middle-aged women
      without radiographic knee osteoarthritis (OA). METHODS: Three-dimensional Vicon
      gait analyses were performed on 20 women who had knee pain but no radiological
      evidence of joint pathology. RESULTS: In multivariate analysis, the peak knee
      adduction moment during the late stance phase of gait was inversely associated
      with knee pain [beta: -10.1 (95% CI -17.6, -2.7), p = 0.01] after adjustment for
      body mass index (BMI) and age. This explained that the knee adduction moment
      during late stance contributed 32% of the variance in knee pain. The peak knee
      adduction moment during early stance was not significantly associated with knee
      pain prior to and after adjustment for BMI and age. CONCLUSION: There is a
      significant inverse association between the peak knee adduction moment during
      late stance and the amount of knee pain experienced by women without radiographic
      evidence of joint pathology. This may represent a compensatory mechanism to
      reduce medial tibiofemoral joint load in the setting of knee pain.

PMID- 16960946
TI  - Revisiting arthritis prevalence projections--it's more than just the aging of the
      population.
AB  - OBJECTIVE: Data for successive population surveys show there is a sustained
      increase in the prevalence of arthritis, surpassing projected estimates. We
      examined whether the often-made assumption of stability in age/sex-specific
      arthritis point-prevalence estimates when estimating future burden is upheld; we
      used nearly a decade of survey data, and computed new projections for arthritis
      prevalence in Canada, taking into account past changes in age/sex-specific
      prevalence estimates and anticipated changes in the age/sex structure of the
      population. The prevalence from 1994 to 2003, overall and by age and sex, was
      documented. METHODS: Analyses were based on persons aged 15+ years from 3 cycles
      of the National Population Health Survey (1994-99; n > 14,000) and 2 cycles of
      the Canadian Community Health Survey (2000-03; n > 130,000). Two projection
      scenarios were adopted to estimate future burden. RESULTS: Stability in age/sex
      point-prevalence estimates was not observed. From 1994 to 2003, absolute and
      relative increases were greatest in the older age groups (55+ yrs) and younger
      age groups (25-54 yrs), respectively. By 2021, we anticipate the prevalence of
      arthritis in Canada will have increased to between 21% and 26%. Overall, the
      prevalence increased from 13.4% to 17.6% from 1994 to 2003, an increase of nearly
      50% in the number of Canadians reporting arthritis. CONCLUSION: The assumption of
      stable age/sex prevalence estimates over time does not hold in Canada. Past
      projections have underestimated future burden; past trends need to be considered.

PMID- 16960947
TI  - Extracranial meningioma presenting as a neck mass in a patient with underlying
      ankylosing spondylitis.
AB  - Extracranial meningiomas are rare. They account for only 2% of meningiomas
      compared to the much more common intracranial site. We describe a rare case of
      extracranial meningioma presenting as a neck lump in a patient with preexisting
      neck disease due to ankylosing spondylitis. Extracranial meningioma should be
      considered in the differential diagnosis of atypical neck lumps. Investigations
      including magnetic resonance imaging and histopathology are discussed, as well as
      the results of a literature review on extracranial meningiomas.

PMID- 16960948
TI  - Pathologic fracture of the hip due to severe gouty arthritis.

PMID- 16960949
TI  - Setting priorities in arthritis care: Care III Conference.
AB  - The disparity between supply and demand in arthritis services can lead to delays
      in diagnosis and access to effective treatments. The focus of 2005 CARE III
      Conference was to develop a research agenda to improve care for people with
      arthritis. Topics included models of care, nonpharmacological/nonsurgical
      interventions for arthritis, and issues around study design, outcome measures and
      knowledge translation and exchange. Seven priority areas emerged from the
      discussion: (1) Develop new, innovative arthritis care strategies; (2) Adapt and
      implement effective service models to address local needs; (3) Understand factors
      related to successful team care; (4) Match patients' needs with appropriate care
      models; (5) Design new or improve outcome measures for participation and quality
      of life; (6) Foster partnerships in sharing research evidence; and (7) Address
      needs for training and quality assurance.

PMID- 16960950
TI  - Team care. Traditions and new trends.
AB  - Major changes have occurred in the care of patients with rheumatic diseases over
      the past decades. Most of these changes have focused on new pharmacological and
      surgical procedures and methods. However, for different reasons, few of these
      methods are available to many patients around the world, and thus other forms of
      care are still needed. For optimal benefit to patients, all aspects of care
      should be organized and coordinated through team care. This leads to new trends
      in team care development and research, based on well established traditions and
      accumulated knowledge.

PMID- 16960951
TI  - Does everybody need a team?
AB  - Multidisciplinary team care, defined as care provided by a group of health
      professionals from various disciplines, has been widely used in arthritis
      management since the 1950s. Its effectiveness in comparison with regular
      outpatient care has mainly been established in patients with rheumatoid arthritis
      (RA). Recent studies have shown that similar outcomes can be achieved in patients
      with RA at lower costs using care provided by a clinical nurse specialist. These
      latter findings suggest that the active components of the multidisciplinary team
      care model may not be related to the number or professional backgrounds of the
      health professionals involved, nor with their physical proximity, but rather to
      the provider's skills in rheumatology and the coordination of services. Because
      many patients with arthritis have healthcare needs that are not met through
      treatment by the rheumatologist alone and since traditional multidisciplinary
      team care in many countries is unavailable or may be undesirable in specific
      situations, the development and evaluation of alternative, comprehensive models
      of care delivery is recommended.

PMID- 16960952
TI  - Current topics on models of care in the management of inflammatory arthritis.
AB  - While there is strong evidence supporting a multidisciplinary team approach in
      arthritis management, access and use are hindered by limited human and financial
      resources. To safeguard the provision of comprehensive care throughout the
      disease trajectory, alternative care models are being developed. Three promising
      arthritis care models include the use of information technology and telemedicine,
      patient initiated care, and extended roles of health professionals. Future
      research projects should focus on: (1) the cost-effectiveness of information
      technology for exchange of patient-based data and education and management
      support; (2) the characteristics and needs of patients who can versus those who
      cannot self-manage; (3) strategies to improve access to care for patients with
      early arthritis, such as extending roles of health professionals to include
      triage; and (4) further structuring and standardizing rheumatology training of
      nursing and allied health professionals.

PMID- 16960953
TI  - Design issues and priorities in team and nonpharmacological arthritis care
      research.
AB  - Nonpharmacologic and team care research present unique design challenges.
      Nonpharmacologic care by nature is multifaceted and complex. Rarely do patients
      receive an intervention in isolation. The delivery of a single or group of
      interventions can be provided by one provider but is frequently provided by
      teams. Therefore, it is imperative that clinical researchers design studies that
      evaluate single and multimodal interventions as well as studies that best
      reproduce the team model of service delivery to accurately examine interventions.
      While it is well accepted that the research question drives the design, it is
      imperative to recognize that certain aspects of nonpharmacologic and team care
      restrict the implementation or effectiveness of specific design components. For
      example, as patients are required to actively engage in lifestyle changes, double
      blinding cannot be employed. In addition, there is no accepted operational
      definition of team care in arthritis. It is important to keep in mind the
      characteristics of these interventions in the selection of a research design and
      develop strategies to best examine these interventions. Combining aspects of
      randomized controlled trials with qualitative methods is one technique to enrich
      data collected on these interventions. Certain features of pharmacovigilance
      studies may also serve as an alternative model. The use of national or regional
      registries for longterm clinical followup as seen in orthopedic surgery may prove
      to be applicable in the design of studies for evaluation of team care. Our
      article will discuss issues related to the design and synthesis of arthritis care
      research, and the role of patients in the design of clinical trials; describe
      collaborative international activities furthering team and nonpharmacological
      arthritis care research; and identify research activities that may influence
      future practice and the health of people with arthritis.

PMID- 16960954
TI  - Outcome measures for arthritis care research: recommendations from the CARE III
      conference.
AB  - The Outcome Measures workshop at CARE III addressed the topic of selecting
      appropriate and relevant outcome measures for research of nonpharmacological,
      nonsurgical interventions. Consumers, practitioners, and researchers contributed
      to small and large group discussions following a series of 7 overview
      presentations. The importance of measuring what matters to consumers using
      measures that match the purpose of research studies was emphasized. It was
      generally agreed that care researchers have access to effective measures of
      disease status, physical and functional status, and quality of life. Gaps exist
      in the repertoire of existing measures, including satisfactory ways to measure
      engagement in more complex roles, the area that has come to be known as
      participation. It was proposed that client-centered outcome measures addressed
      this gap, but only in part. Research priorities proposed that new or improved
      outcome measures be designed for participation in employment, parenting, social
      relationships, leisure, and school, and that more attention be given to process
      measures that capture the mediating factors associated with improved health
      outcomes.

PMID- 16960955
TI  - Intraarticular injection of infliximab.

PMID- 16960956
TI  - Seasonal variation of primary neuropsychiatric systemic lupus erythematosus.

PMID- 16960959
TI  - Bosentan improves functional class, pulmonary artery systolic pressure, and DLCO
      in scleroderma patients with pulmonary hypertension: a possible synergy with
      iloprost.

PMID- 16960961
TI  - Leflunomide for relapsing polychondritis: successful longterm treatment.

PMID- 16960963
TI  - Infliximab-associated pneumonitis in rheumatoid arthritis.

PMID- 16960964
TI  - Thermographic and symptomatic effect of a single dose of sildenafil citrate on
      Raynaud's phenomenon in patients with systemic sclerosis: a potential treatment.

PMID- 16960965
TI  - Patients know it: Hughes syndrome is unique.

PMID- 16960966
TI  - WinBEST-KIT: Windows-based biochemical reaction simulator for metabolic pathways.
AB  - We have implemented an efficient, user-friendly biochemical reaction simulator
      called Web-based BEST-KIT (Biochemical Engineering System analyzing Tool-KIT) for
      analyzing large-scale nonlinear networks such as metabolic pathways. Users can
      easily design and analyze an arbitrary reaction scheme through the Internet and
      an efficient graphical user interface without considering the mathematical
      equations. The reaction scheme can include several reaction types, which are
      represented by both the mass action law (mass balance) and approximated velocity
      functions of enzyme kinetics at steady state, such as Michaelis-Menten, Hill
      cooperative, Competitive inhibition. However, since all modules in Web-based BEST
      KIT have been developed in Java applet style, users cannot optionally make use of
      original mathematical equations in addition to the prepared equations. In the
      present study, we have developed a new version of BEST-KIT (for Microsoft Windows
      called WinBEST-KIT) to allow users to define original mathematical equations and
      to customize these equations very easily as user-defined reaction symbols. The
      following powerful system-analytical methods are prepared for system analysis:
      time-course calculation, parameter scanning, estimation of the values of unknown
      kinetic parameters based on experimentally observed time-course data of
      reactants, dynamic response of reactants against virtual external perturbations,
      and real-time simulation (Virtual Dry Lab).

PMID- 16960967
TI  - A note on phasing long genomic regions using local haplotype predictions.
AB  - The common approaches for haplotype inference from genotype data are targeted
      toward phasing short genomic regions. Longer regions are often tackled in a
      heuristic manner, due to the high computational cost. Here, we describe a novel
      approach for phasing genotypes over long regions, which is based on combining
      information from local predictions on short, overlapping regions. The phasing is
      done in a way, which maximizes a natural maximum likelihood criterion. Among
      other things, this criterion takes into account the physical length between
      neighboring single nucleotide polymorphisms. The approach is very efficient and
      is applied to several large scale datasets and is shown to be successful in two
      recent benchmarking studies (Zaitlen et al., in press; Marchini et al., in
      preparation). Our method is publicly available via a webserver at
      http://research.calit2.net/hap/.

PMID- 16960968
TI  - ANGLE: a sequencing errors resistant program for predicting protein coding
      regions in unfinished cDNA.
AB  - In the process of making full-length cDNA, predicting protein coding regions
      helps both in the preliminary analysis of genes and in any succeeding process.
      However, unfinished cDNA contains artifacts including many sequencing errors,
      which hinder the correct evaluation of coding sequences. Especially, predictions
      of short sequences are difficult because they provide little information for
      evaluating coding potential. In this paper, we describe ANGLE, a new program for
      predicting coding sequences in low quality cDNA. To achieve error-tolerant
      prediction, ANGLE uses a machine-learning approach, which makes better expression
      of coding sequence maximizing the use of limited information from input
      sequences. Our method utilizes not only codon usage, but also protein structure
      information which is difficult to be used for stochastic model-based algorithms,
      and optimizes limited information from a short segment when deciding coding
      potential, with the result that predictive accuracy does not depend on the length
      of an input sequence. The performance of ANGLE is compared with ESTSCAN on four
      dataset each of them having a different error rate (one frame-shift error or one
      substitution error per 200-500 nucleotides) and on one dataset which has no
      error. ANGLE outperforms ESTSCAN by 9.26% in average Matthews's correlation
      coefficient on short sequence dataset (< 1000 bases). On long sequence dataset,
      ANGLE achieves comparable performance.

PMID- 16960969
TI  - An automated procedure for the extraction of metabolic network information from
      time series data.
AB  - Novel high-throughput measurement techniques in vivo are beginning to produce
      dense high-quality time series which can be used to investigate the structure and
      regulation of biochemical networks. We propose an automated information
      extraction procedure which takes advantage of the unique S-system structure and
      supports model building from time traces, curve fitting, model selection, and
      structure identification based on parameter estimation. The procedure comprises
      of three modules: model Generation, parameter estimation or model Fitting, and
      model Selection (GFS algorithm). The GFS algorithm has been implemented in MATLAB
      and returns a list of candidate S-systems which adequately explain the data and
      guides the search to the most plausible model for the time series under study. By
      combining two strategies (namely decoupling and limiting connectivity) with
      methods of data smoothing, the proposed algorithm is scalable up to realistic
      situations of moderate size. We illustrate the proposed methodology with a
      didactic example.

PMID- 16960971
TI  - Improving the sensitivity and specificity of protein homology search by
      incorporating predicted secondary structures.
AB  - In this paper, we improve the homology search performance by the combination of
      the predicted protein secondary structures and protein sequences. Previous
      research suggested that the straightforward combination of predicted secondary
      structures did not improve the homology search performance, mostly because of the
      errors in the structure prediction. We solved this problem by taking into account
      the confidence scores output by the prediction programs.

PMID- 16960970
TI  - Similarities of ordered gene lists.
AB  - MOTIVATION: Many applications of microarray technology in clinical cancer studies
      aim at detecting molecular features for refined diagnosis. In this paper, we
      follow an opposite rationale: we try to identify common molecular features shared
      by phenotypically distinct types of cancer using a meta-analysis of several
      microarray studies. We present a novel algorithm to uncover that two lists of
      differentially expressed genes are similar, even if these similarities are not
      apparent to the eye. The method is based on the ordering in the lists. RESULTS:
      In a meta-analysis of five clinical microarray studies we were able to detect
      significant similarities in five of the ten possible comparisons of ordered gene
      lists. We included studies, where not a single gene can be significantly
      associated to outcome. The detection of significant similarities of gene lists
      from different microarray studies is a novel and promising approach. It has the
      potential to improve upon specialized cancer studies by exploring the power of
      several studies in one single analysis. Our method is complementary to previous
      methods in that it does not rely on strong effects of differential gene
      expression in a single study but on consistent ones across multiple studies.

PMID- 16960972
TI  - On the inference of parsimonious indel evolutionary scenarios.
AB  - Given a multiple alignment of orthologous DNA sequences and a phylogenetic tree
      for these sequences, we investigate the problem of reconstructing a most
      parsimonious scenario of insertions and deletions capable of explaining the gaps
      observed in the alignment. This problem, called the Indel Parsimony Problem, is a
      crucial component of the problem of ancestral genome reconstruction, and its
      solution provides valuable information to many genome functional annotation
      approaches. We first show that the problem is NP-complete. Second, we provide an
      algorithm, based on the fractional relaxation of an integer linear programming
      formulation. The algorithm is fast in practice, and the solutions it produces
      are, in most cases, provably optimal. We describe a divide-and-conquer approach
      that makes it possible to solve very large instances on a simple desktop machine,
      while retaining guaranteed optimality. Our algorithms are tested and shown
      efficient and accurate on a set of 1.8 Mb mammalian orthologous sequences in the
      CFTR region.

PMID- 16960973
TI  - Applying Robust Directional Similarity based Clustering approach RDSC to
      classification of gene expression data.
AB  - Despite the fact that the classification of gene expression data from a cDNA
      microarrays has been extensively studied, nowadays a robust clustering method,
      which can estimate an appropriate number of clusters and be insensitive to its
      initialization has not yet been developed. In this work, a novel Robust
      Clustering approach, RDSC, based on the new Directional Similarity measure is
      presented. This new approach RDSC, which integrates the Directional Similarity
      based Clustering Algorithm, DSC, with the Agglomerative Hierarchical Clustering
      Algorithm, AHC, exhibits its robustness to initialization and its capability to
      determine the appropriate number of clusters reasonably. RDSC has been
      successfully employed to both artificial and benchmarking gene expression
      datasets. Our experimental results demonstrate its distinctive superiority over
      the conventional method Kmeans and the two typical directional clustering
      algorithms SPKmeans and moVMF.

PMID- 16960974
TI  - An amino acid substitution matrix for protein conformation identification.
AB  - Amino acid substitution matrices play an essential role in protein sequence
      alignment, a fundamental task in bioinformatics. Most widely used matrices, such
      as PAM matrices derived from homologous sequences and BLOSUM matrices derived
      from aligned segments of PROSITE, did not integrate conformation information in
      their construction. There are a few structure-based matrices, which are derived
      from limited data of structure alignment. Using databases PDB_SELECT and DSSP, we
      create a database of sequence-conformation blocks which explicitly represent
      sequence-structure relationship. Members in a block are identical in conformation
      and are highly similar in sequence. From this block database, we derive a
      conformation-specific amino acid substitution matrix CBSM60. The matrix shows an
      improved performance in conformational segment search and homolog detection.

PMID- 16960975
TI  - The role of the mitochondria in human aging and disease: from gene to cell
      signaling. Proceedings of the second scientific meeting of the Asian Society for
      Mitochondrial Research and Medicine. April 1-2, 2004. Taipei, Taiwan.

PMID- 16960976
TI  - Novel agents in the treatment of lung cancer: advances in EGFR-targeted agents.
      Proceedings of the Third Cambridge Conference. September 23-24, 2005. Cambridge,
      Massachusetts, USA.

PMID- 16960977
TI  - UV exposure guidance: a balanced approach between health risks and health
      benefits of UV and vitamin D. Proceedings of an international workshop,
      International Commission on Non-ionizing Radiation Protection. October 17-18,
      2005. Munich, Germany.

PMID- 16960978
TI  - Dasatinib in chronic myelogenous leukemia.

PMID- 16960979
TI  - Vitamins C and E and the prevention of preeclampsia.

PMID- 16960980
TI  - Measured and estimated glomerular filtration rate.

PMID- 16960981
TI  - Hematopoietic stem-cell transplantation.

PMID- 16960982
TI  - 5-hydroxytryptamine receptors in the human cardiovascular system.
AB  - The human cardiovascular system is exposed to plasma 5-hydroxytryptamine (5-HT,
      serotonin), usually released from platelets. 5-HT can produce harmful acute and
      chronic effects. The acute cardiac effects of 5-HT consist of tachycardia
      (preceded on occasion by a brief reflex bradycardia), increased atrial
      contractility and production of atrial arrhythmias. Acute inotropic, lusitropic
      and arrhythmic effects of 5-HT on human ventricle become conspicuous after
      inhibition of phosphodiesterase (PDE) activity. Human cardiostimulation is
      mediated through 5-HT4 receptors. Atrial and ventricular PDE3 activity exerts a
      protective role against potentially harmful cardiostimulation. Chronic exposure
      to high levels of 5-HT (from metastatic carcinoid tumours), the anorectic drug
      fenfluramine and its metabolites, as well as the ecstasy drug 3,4
      methylenedioxymethamphetamine (MDMA) and its metabolite 3,4
      methylenedioxyamphetamine (MDA) are associated with proliferative disease and
      thickening of cardiac valves, mediated through 5-HT2B receptors. 5-HT2B receptors
      have an obligatory physiological role in murine cardiac embryology but whether
      this happens in humans requires research. Congenital heart block (CHB) is, on
      occasion, associated with autoantibodies against 5-HT4 receptors. Acute vascular
      constriction by 5-HT is usually shared by 5-HT1B and 5-HT2A receptors, except in
      intracranial arteries which constrict only through 5-HT1B receptors. Both 5-HT1B
      and 5-HT2A receptors can mediate coronary artery spasm but only 5-HT1B receptors
      appear involved in coronary spasm of patients treated with triptans or with
      Prinzmetal angina. 5-HT2A receptors constrict the portal venous system including
      oesophageal collaterals in cirrhosis. Chronic exposure to 5-HT can contribute to
      pulmonary hypertension through activation of constrictor 5-HT1B receptors and
      proliferative 5-HT2B receptors, and possibly through direct intracellular
      effects.

PMID- 16960983
TI  - Synthetic high density lipoproteins for the treatment of myocardial
      ischemia/reperfusion injury.
AB  - Synthetic high density lipoproteins (sHDL) are discoidal lipoprotein particles
      made of an apolipoprotein and a phospholipid, which mimic most, if not all, of
      the atheroprotective properties of plasma HDL, including stimulation of reverse
      cholesterol transport (RCT), prevention of endothelial dysfunction, and
      inhibition of lipid oxidation. sHDL are currently under development as a novel
      treatment for atherosclerotic cardiovascular disease. A number of preclinical
      studies have demonstrated the ability of single or multiple injections of sHDL to
      induce the regression of atherosclerotic plaques and prevent arterial restenosis.
      In the first phase II trial in patients with acute coronary syndromes, a short
      term treatment with sHDL containing the disulfide-linked dimer of the
      apolipoprotein A-IMilano variant (A-IM/A-IM) caused a remarkable reduction of
      atheroma volume. sHDL also display a direct cardioprotective activity in ex vivo
      and in vivo models of myocardial ischemia/reperfusion (I/R) injury, and may
      become a useful adjunctive therapy to improve clinical outcomes in patients with
      acute coronary syndromes or undergoing coronary procedures.

PMID- 16960984
TI  - Introduction to the newborn screening fact sheets.
AB  - Newborn screening fact sheets were last revised in 1996 by the Committee on
      Genetics of the American Academy of Pediatrics. These fact sheets have been
      revised again because of advances in the field, including technologic innovations
      such as tandem mass spectrometry, as well as greater appreciation of ethical
      issues such as informed consent. The fact sheets provide information to assist
      pediatricians and other professionals who care for children in performing their
      essential role within the newborn screening public health system. The newborn
      screening system consists of 5 parts: (1) newborn testing; (2) follow-up of
      abnormal screening results to facilitate timely diagnostic testing and
      management; (3) diagnostic testing; (4) disease management, which requires
      coordination with the medical home and genetic counseling; and (5) continuous
      evaluation and improvement of the newborn screening system. The following
      disorders are reviewed in the newborn screening fact sheets (which are available
      at www.pediatrics.org/cgi/content/full/118/3/e934): biotinidase deficiency,
      congenital adrenal hyperplasia, congenital hearing loss, congenital
      hypothyroidism, cystic fibrosis, galactosemia,homocystinuria, maple syrup urine
      disease, medium-chain acyl-coenzyme A dehydrogenase deficiency, phenylketonuria,
      sickle cell disease and other hemoglobinopathies,and tyrosinemia.

PMID- 16960985
TI  - Colo. losing last Medicaid HMO. 65,000-member plan will close by end of August.

PMID- 16960986
TI  - Consolidating resources. AmerisourceBergen deal will create no. 2 player.

PMID- 16960987
TI  - Workers get stake. Memphis hospital converts to employee stock plan.

PMID- 16960989
TI  - Congress: what standards? Health IT bill would curb some HHS regulations.

PMID- 16960990
TI  - Survey says: Grassley steamed. 35 not-for-profits opt out of voluntary GAO comp
      study.

PMID- 16960991
TI  - The wait goes on. Patient Safety Act still not implemented after a year.

PMID- 16960992
TI  - Feds investigating devicemakers. Experts predict Medtronic settlement is first of
      many.

PMID- 16960993
TI  - Caps cause worries. Doc payments could be limited for imaging.

PMID- 16960994
TI  - Endoscopic appearance of annular pancreas in a patient with Schinzel-Giedon
      syndrome.

PMID- 16960995
TI  - Measles outbreak and response in Fiji, February-May 2006.

PMID- 16960996
TI  - Performance of acute flaccid paralysis (AFP) surveillance and incidence of
      poliomyelitis, 2005-2006 (data received in WHO headquarters as of 22 August
      2006).

PMID- 16960997
TI  - Is that lab necessary?

PMID- 16960999
TI  - [Acute myocarditis and death--are we always late?].

PMID- 16960998
TI  - [Unexpected sudden death after percutaneous coronary intervention].
AB  - BACKGROUND: Myocarditis is one of several important differential diagnoses in
      patients presenting with chest pain or symptoms of heart failure. The prevalence
      of myocarditis is probably underestimated. In young patients with sudden cardiac
      death, myocarditis is a common finding at autopsy. MATERIAL AND METHODS: A
      previously healthy 54-year-old man presented with a first episode of chest pain.
      Smoking was the only risk factor for coronary artery disease. RESULTS: Plasma
      levels of both Troponin-I and CK-MB mass were negative at admission, but were
      elevated in a second sample. A subtotal stenosis in the left anterior descending
      artery was treated with PCI. The patient was discharged after four days. He was
      found dead at home six days after PCI. Autopsy revealed a massive myocarditis, no
      signs of myocardial necrosis and only minor coronary artery disease.
      INTERPRETATION: This case illustrates the importance of keeping less frequent
      differential diagnoses in mind when patients present with chest pain. Also, this
      case underscores the importance of keeping a high autopsy rate; for feedback to
      clinicians, for correct cause-of-death statistics and for research.

PMID- 16961000
TI  - Should I have been killed at birth?

PMID- 16961001
TI  - The stuttering doctor's 'monster study'.

PMID- 16961002
TI  - The environmental and occupational health sciences.

PMID- 16961003
TI  - Changes in blood trihalomethane concentrations resulting from differences in
      water quality and water use activities.
AB  - Water disinfection is extremely important for the protection of public health;
      however, it also forms by-products, including trihalomethanes (THMs). Previous
      studies of health effects from disinfection by-products have lacked accurate
      methods to quantify exposure over time. As a first step in establishing a better
      system for exposure assessment, the authors investigated which household water
      use activities cause a significant increase in internal dose concentrations of
      THMs. In this study, 7 subjects in 2 different cities carried out 12 common
      activities that involved water use. In 3 of these activities-bathing, showering,
      and washing dishes by hand-the blood concentrations of THMs increased
      substantially. Further analysis of the data suggested that tap water
      concentrations primarily controlled the blood concentrations from bathing
      exposure, whereas tap water concentrations and ambient air concentrations
      resulting from water use affected the blood concentrations from showering
      exposure. Further studies will focus on variables in these activities that can
      alter exposure.

PMID- 16961004
TI  - Genetic influences on the retention of inorganic mercury.
AB  - Mercury is eliminated as glutathione (GSH) conjugates. GSH production is mediated
      by glutamyl-cysteine ligase (GCL), and conjugation by glutathione S-transferases
      (GST). This study tested if polymorphisms in GCL and GST genes modify mercury
      retention in humans exposed to elemental mercury vapor. Total mercury
      concentrations in whole blood, plasma and urine, and genotypes for GCLC, GCLM,
      GSTA1, GSTM1, GSTP1, and GSTT1 were determined in 309 gold miners, gold buyers
      and controls. The presence of the GCLM-588T allele was associated with increased
      blood, plasma and urine mercury levels. These results indicate that genotypes
      with decreased GSH availability for mercury conjugation affect the metabolism of
      inorganic mercury.

PMID- 16961005
TI  - Childhood lead poisoning in Washington state: A statewide survey.
AB  - Although childhood lead poisoning is an important health issue in the United
      States, it is not distributed evenly across the country. To estimate the
      prevalence of childhood lead poisoning in Washington State, the authors conducted
      a birth certificate follow-back survey of 1- to 2-year-old children. Interviewers
      visited participating families at their homes to conduct blood lead tests with a
      portable testing device. The estimated prevalence of lead poisoning for all 1- to
      2-year-old children in the state was 0.9% (95% confidence interval [CI]: 0.3
      2.7); for Hispanic children in central Washington, it was 3.7% (95% CI: 1.3
      10.2), and their risk of lead poisoning was significantly higher than that of all
      other children in the state (relative risk [RR] = 5.8, 95% CI: 1.3-24.9). Lead
      poisoning prevalence in Washington State children is lower than the US average
      and is highest among Hispanic children in central Washington.

PMID- 16961006
TI  - Environmental determinants of Parkinson's disease.
AB  - Increasing toxicologic and epidemiologic evidence suggests that pesticides and
      other environmental exposures are associated with idiopathic Parkinson's disease.
      Using a case-control study, the authors examined the impact of farming, pesticide
      use, rural residence, and well water use (including critical periods of childhood
      exposure) on the risk of Parkinson's disease. After adjustment for confounding, >
      or = 40 years of well-water exposure (compared to no well water use) was
      associated with an increased risk of Parkinson's disease (OR = 7.1; 95% CI: 2.3
      22.1). The authors found an increased risk of Parkinson's disease (OR = 2.1; 95%
      Cl: 0.7-6.4) for well water use during the first 20 years of life (compared with
      <20 years of exposure) and saw some suggestion of an exposure-response
      relationship with increasing childhood exposure. Farming and pesticide use
      (occupational or residential) was not associated with Parkinson's disease but
      exposure assessment limitations warrant further investigation.

PMID- 16961007
TI  - Application of real-time particle sensors to help mitigate exposures of wildland
      firefighters.
AB  - High particulate exposures have been demonstrated to decrease lung function among
      firefighters. In this article, the authors demonstrated the feasibility of using
      small real-time particle sensors to inform wildland firefighters so they may make
      informed decisions on the use of personal respiratory protection. Using 1 mg/m3
      as an indicator point for use of appropriately designed respiratory protection,
      such sensors could help prevent 16% to 74% of particulate exposure during
      prescribed burns when firefighters assess exposure as low or medium. Adherence to
      such a guideline for the use of respiratory protection would involve its
      deployment during 3% to 22% of individual 8-hour shifts. In addition, data
      logging sensors would provide a valuable tool for tracking exposure to
      particulates among wildland firefighters for occupational health monitoring.

PMID- 16961008
TI  - Blood lead concentrations in maternal and cord blood evaluated by two analytic
      methods.
AB  - In this study the authors determined the relationship between blood lead
      concentrations in pregnant women and newborns, using graphite furnace atomic
      absorption spectrometry (GFAAS) and the LeadCare System (LCS). Fifty-five
      pregnant women admitted for delivery from June to August 2002 at a hospital in
      Brazil were included in the study. Blood samples were taken from the women and
      from umbilical cords to determine serum lead concentrations. Only 3 women had
      blood lead concentrations > or = 0.48 micromol/L. There were correlations between
      lead concentrations in women and newborns using either GFAAS (r = 0.83, p < .001)
      or the LCS (r = 0.75, p < .001). However, there were no statistically significant
      correlations between the GFAAS and LCS methods, probably because most of the
      women did not have high concentrations of lead (> or = 0.48 micromol/L).
      Considering the discrepancy the authors found between the LCS method and the
      traditional GFAAS method, the authors advise against using the LCS method,
      especially in populations with levels of lead < or = 0.48 micromol/L.

PMID- 16961009
TI  - Risk of cancer as a result of community exposure to gasoline vapors.

PMID- 16961010
TI  - Operant conditioning and some aspects of the psychotherapeutic process.
AB  - Operant conditioning studies demonstrate that an experimenter can alter the
      content of verbal communication and other forms of behaviour by the use of
      minimal cues. Most important is that this can take place without the conscious
      awareness on the part of the subject. Parallels between studies of operant
      conditioning and of psychotherapy suggest that operant conditioning may be one of
      the mechanisms mediating change during psychotherapy without either therapist or
      patient knowing that this is so. Application of this postulate to the
      psychotherapeutic process integrates some clinical and experimental findings and
      should prove a useful addition to the psychotherapist's understanding of factors
      operative in the psychotherapeutic process.

PMID- 16961011
TI  - Operant conditioning of schizophrenic children.
AB  - Though there is little agreement concerning the diagnosis, incidence or etiology
      of childhood schizophrenia, until recently most authors agree there is no
      effective treatment. Operant conditioning is reported to succeed where other
      therapies have failed. Twenty children diagnosed according to Creak's criteria in
      two groups matched for age, sex, duration of stay, Vineland score and amount of
      speech, were treated by either interpretive play therapy or operant conditioning.
      Emotional relatedness and self-identity, then imitation of behaviour and speech
      were conditioned with the positive reinforcements of candy. Tested before, during
      and after fifty 45-minute sessions, those in the operant-conditioning group had
      gained more speech and improved more on Vineland score. The relative efficacy of
      operant conditioning may be related to the greater ease with which the staff
      learned this technique and the need of these children for predictable routines.
      The experiment will continue with a crossover complex.

PMID- 16961012
TI  - The role of punishment in the in-patient treatment of psychiatrically disturbed
      children.
AB  - The role of punishment in the psychiatric in-patient treatment of nonpsychotic
      latency-age children with behaviourdisorders is discussed. Punishment is defined
      as the removal of previously existing positive reinforcers or the administration
      of aversive stimuli. Ways in which appropriate social behaviour may be acquired
      are briefly considered. These include reinforcement of desirable responses, non
      reinforcement of undesirable responses, reinforcement of incompatible responses
      and imitative learning. The reported effects of punishment on behaviour are
      reviewed and the psychological functions necessary before punishment can have the
      intended effects considered. For seriously disturbed children punishment is
      ineffective as a treatment technique. It reinforces pathological perceptions of
      self and adults even if it successfully suppresses behaviour. The frame of
      reference of the seriously disturbed child contraindicates the removal of
      positive reinforcers and verbal as well as physical aversive stimuli. Controls
      and punishments must be clearly distinguished. Controls continue only as long as
      the behaviour towards which they are directed. They do not include the deliberate
      establishment of an unpleasant state by the adult as a result of particular
      behaviour. Control techniques such as removal from a group may be necessary but
      when possible should be avoided in favour of techniques less likely to be
      misinterpreted. Avoidance of punishment in treatment makes even more important
      explicit expectations and provision of realistic controls. Natural laws may
      result in unpleasant experiences as an unavoidable result of certain behaviour.
      By definition such results can never be imposed by the adult. Treatment
      considerations may necessitate that the child be protected from the results of
      his actions. Avoidance of punishment requires a higher staff/child ratio, more
      mature and better trained staff. Sometimes children have previously been deterred
      from serious community acting out only by punishment. Should the therapeutic
      endeavours outlined not prevent such behaviour, treatment in a closed setting
      without punishment is indicated, not the use of punishment in an open centre.

PMID- 16961013
TI  - Treatment of a case of school phobia by reciprocal inhibition.
AB  - Behaviour therapy by reciprocal inhibition was undertaken on a moderately severe
      case of school phobia in an 11-year-old boy after an adequate trial of
      conventional therapy had failed to bring about lasting improvement. A fairly
      accurate estimate of expended therapy time follows: First admission to day-school
      (January 1964): Five initial sessions (30 minutes each) of relaxation by
      hypnosis. Eighteen sessions (20-30 minutes each) of reciprocal inhibition
      therapy, presenting an average of four hierarchies per session. Second admission
      to day-school (September 1964): Fifteen sessions (20-30 minutes each) of
      reciprocal inhibition therapy, presenting an average of seven hierarchies per
      session. This form of therapy was undertaken as a learning experience by the
      author and its very good results are in no way meant to imply that one approach
      is superior to another. Rather, this paper was prepared as a plea for tolerance
      on the part of all who concern themselves with the treatment of emotionally
      disturbed persons.

PMID- 16961014
TI  - RNA and memory: a re-evaluation of present data.
AB  - Studies on the beneficial effects of yeast RNA treatment on learning and memory
      in senile patients and in animal experimentation are reviewed in this paper.
      Experimental evidence is cited showing that yeast RNA is not incorporated into
      brain tissue and does not increase brain synthetic activity. Thus the therapeutic
      effects of RNA treatment cannot be explained in direct relation to the hypothesis
      that RNA within the brain encodes memory information. Evidence for stimulant
      action of RNA, mediated by uric acid, its primary metabolite, is presented as the
      basis for an alternative theory which would explain RNA action in pharmacological
      terms.

PMID- 16961015
TI  - Cytogenetic practice in a mental retardation clinic.
AB  - Chromosome abnormalities are known to be associated with a wide variety of
      psychiatric disorders varying from severe mental retardation to aberrant social
      behaviour. Principles and methods used in contemporary cytogenetic laboratories
      are discussed and an attempt is made to illustrate how the integration of these
      techniques can be of considerable value for diagnostic and genetic counselling
      purposes.

PMID- 16961016
TI  - Psychiatric implications of religious conversion.
AB  - Some of the literature concerning religious phenomena and conversion experience
      is reviewed. Three cases have been described in which there are several common
      factors leading to religious conversion - a specific unconscious conflict, a
      conscious conflict with which the individual is actively struggling, adolescence,
      and a fundamentalist religious belief. The cases presented are examples of each
      of three possible solutions to the patient's conflictual dilemma. A central
      feature of the psychodynamics in these cases is the resolution of an (Edipal
      conflict through delayed identification with the parent of the opposite sex.

PMID- 16961017
TI  - [Fencing in schizophrenia, technique of readaptation -- preliminary report].

PMID- 16961018
TI  - Collaboration between psychologists and psychiatrists in psychotherapy.

PMID- 16961019
TI  - Some comments on family and individual therapy.

PMID- 16961020
TI  - Cardiac symptoms and tachistoscopic recognition of the heart image.
AB  - This study investigates the relationship between cardiac symptoms and an
      individual's tachistoscopic awareness of the heart image. A group of 78 female
      college students were classified on the basis of heart symptomatology utilizing
      self-administered medical questionnaires. It was found that symptomatic subjects
      with more frequent disturbances required significantly longer to recognize an
      illustration of the heart. It was hypothesized that these subjects were less
      tachistoscopically aware of the heart image because of anxiety associated with
      this body area.

PMID- 16961021
TI  - A note on body movement during understimulation.

PMID- 16961022
TI  - Ernest Jones in Toronto--Part III. Publications by Ernest Jones, M.D. 1908-1913.

PMID- 16961023
TI  - Society's changing attitude to the idiot.

PMID- 16961024
TI  - Is opportunistic oral cancer screening by dentists feasible? An analysis of the
      patterns of dental attendance of a nationally representative sample over 10
      years.
AB  - OBJECTIVES: To assess whether or not opportunistic oral cancer screening by
      dentists to detect pre-malignant or early cancer lesions is feasible. The
      objective was to analyse the patterns of dental attendance of a national
      representative sample over a period of 10 years to ascertain whether individuals
      at high-risk of oral cancer would be accessible for opportunistic oral cancer
      screening. METHODS: Secondary analysis of data extracted from the British
      Household Panel Survey, a national longitudinal survey (n=5547). Analysis to
      ascertain whether patterns of attendance for dental check-ups for a period of 10
      years (1991-2001) were associated with risk factors for oral cancer such as age,
      sex, education, social class, smoking status and smoking intensity. RESULTS:
      Males, aged over 40 years, less educated manual workers and smokers were
      significantly less likely to attend for dental check-ups compared with females
      and younger, higher educated, higher socio-economic class non-smokers (p < 0.05).
      Throughout the 10-year period, young people, more than older people, had
      progressively lower odds ratios of attending. Those with more education used
      dental services more. Heavy smokers were infrequent attendees. CONCLUSIONS: This
      study suggests that opportunistic oral cancer screening by dentists is not
      feasible to include high-risk groups as they are not regular attendees over 10
      years. Those who would be screened would be the low-risk groups. However,
      dentists should continue screening all patients as oral precancers are also found
      in regular attendees. More should be done to encourage the high-risk groups to
      visit their dentists.

PMID- 16961025
TI  - Oral health status of children with syndromic craniosynostosis.
AB  - OBJECTIVE: To gain more information on the oral health status of subjects with
      syndromic craniosynostosis. DESIGN: A cross-sectional study. MATERIALS AND
      METHODS: The present study took place at the Hospital for Rehabilitation of
      Craniofacial Anomalies of University of Sao Paulo (HRAC-USP). The sample was 19
      patients with syndromic craniosynostosis (10 Apert, 5 Crouzon, 2 Pfeiffer and 2
      Saethre-Chotzen), aged 5 to 15 years. An assessment of plaque, caries and
      gingival indices, and evaluation of the efficacy of toothbrushing was carried
      out. The measurements included PHP index, dmft and DMFT indices, gingival index,
      comparison of PHP before and after non-supervised toothbrushing and between
      individuals with and without severe syndactyly. RESULTS: The patients displayed
      high plaque index and poor efficacy of toothbrushing, regardless of the presence
      of severe syndactyly; despite the plaque accumulation, the gingival index was not
      proportionally high. There was predominance of the D component for the DMFT
      index, which combined with the need for restorative treatment in 42.1% of the
      patients indicates poor access to dental care by these patients. CONCLUSIONS: The
      results show the need for a dental follow-up programme for these patients. Carers
      should be informed of the importance in aiding these patients during
      accomplishment of oral hygiene at home.

PMID- 16961026
TI  - Occlusal/dental anomalies found in a random sample of Nigerian schoolchildren.
AB  - OBJECTIVE: The aim of this study was to assess the occlusal/dental anomalies
      needing early treatment for maximal occlusal development among 11-12-year-olds in
      Ibadan, Nigeria. MATERIALS AND METHODS: An epidemiological survey of 361 school
      students, 171 (47.4%) males and 190 (52.6%) females, was carried out in Ibadan,
      Nigeria. Subjects were randomly selected from different schools in the city. One
      examiner, under natural illumination in the school premises, examined all the
      children. RESULTS: Prolonged retention of primary teeth with displacement of the
      permanent series was observed in 4.2% while dental anterior cross bite accounted
      for 5.5%. Oral habits with their deleterious effects on the occlusion were noted
      in 5.0%. Other findings were: clinically missing permanent teeth, 3.6%;
      supernumerary teeth, 1.4%; double teeth, 1.9%; carious lesions, 6.9%; conically
      shaped lateral incisors, 1.4%; and transposition, 0.6%. Proclination of the upper
      incisors with increased overjets of more than 5mm, as well as some fractures of
      the incisors, accounted for 22.4%. In all, 51.8% had one form of occlusal/dental
      need or another. No statistically significant gender differences were observed
      for all the various needs (p > 0.05) except the prevalence of supernumerary
      teeth, which was statistically higher in males (p < 0.05). CONCLUSION: Over half
      of the children could benefit from one interceptive need or the other for proper
      occlusal development. Routine dental check ups are very much encouraged in
      developing countries like Nigeria, as in other developed parts of the world.

PMID- 16961027
TI  - Trends in dental caries rates in 12- and 13-year-old schoolchildren from
      Florianopolis (Brazil) between 1971 and 2005.
AB  - PURPOSE: To estimate dental caries prevalence and severity among all 12- and 13
      year-old schoolchildren enrolled in a public school in 2005 and to establish
      comparisons with the results of studies previously conducted in the same school
      in 1971, 1997 and 2002. METHODS: A cross-sectional study involving 190 children
      was carried out. A single calibrated examiner collected the clinical data
      according to the World Health Organization (1997) criteria. RESULTS: The response
      rate was 90.0%. Between 1971 and 2005, the observed reduction in caries
      prevalence was 58.2%, whereas the mean DMFT Index declined from 9.2 to 0.8, which
      corresponds to a reduction of 91.3%. The significant caries index (SiC) reduced
      from 3.4 (CI 95% 3.0-3.8) in 2002 to 2.2 (CI 95% 1.8-2.5) in 2005. CONCLUSION:
      This study indicates an actual decline in dental caries prevalence and severity
      among the schoolchildren during the studied period, even though different
      diagnostic criteria were used.

PMID- 16961028
TI  - Trends in caries experience and fluorosis prevalence in 11- to 12-year-old
      Brazilian children between 1991 and 2004.
AB  - Investigating dental caries and fluorosis prevalence over time is an important
      measure for monitoring trends in oral health. PURPOSE: This work aimed to
      describe the prevalence of dental caries and dental fluorosis of 11- to 12-year
      old schoolchildren from Iracemapolis, Brazil, in 2004 (n=236) and to compare the
      current prevalence rates with those from previous surveys carried out in 1991
      (n=200), 1995 (n=160), 1997 (n=314) and 2001 (n=244). MATERIALS AND METHODS: The
      schoolchildren of both genders from all public schools were examined by two
      calibrated dentists (Kappa > 0.81), using dental probes and buccal mirrors under
      natural light in an outdoor setting. Dental caries and fluorosis were measured
      using the DMFT and Thylstrup-Fejerskov (T-F) indexes, respectively. The variation
      of DMFT index over time was assessed by analysis of regression and the fluorosis
      prevalence (T-F>1) was compared over time by the Chi-square test at 5%
      significance level. RESULTS: In 2004, the mean value for DMFT was 1.2; 50% of the
      children were caries-free, and 15.7% presented dental fluorosis (T-F>1). A
      significant caries reduction (82.1%) and a significant increase (685%) of
      fluorosis prevalence have been observed from 1991 to 2004 (p < 0.01). CONCLUSION:
      The results suggest a continuous decrease of dental caries experience and an
      increase of dental fluorosis prevalence in 11-to 12-year-old schoolchildren from
      this Brazilian town as well as indicate that further epidemiological surveys
      should be carried out in order to monitor these trends.

PMID- 16961029
TI  - Prevalence of dental caries in schoolchildren living in rural and urban areas:
      results from the first region-wide Italian survey.
AB  - PURPOSE: The collection of comprehensive epidemiological data for dental caries
      of Italian schoolchildren in both rural and urban areas. MATERIALS AND METHODS:
      The dft and DMFT indices were recorded from 27163 6-to-9-year-old children
      attending the primary schools of Abruzzo, a region of Central Italy, according to
      the World Health Organization recommendations. RESULTS: The number of surveyed
      children were 5413, 8359, 8362 and 5026 in the 6-, 7-, 8- and 9-year-old groups
      respectively; the percentages of children positive for caries were 39.5, 48.3,
      54.4 and 60.8 respectively. The mean dft (SD) values of the age groups were 1.57
      (2.67), 1.79 (2.59), 1.88 (2.47) and 2.02 (2.45) respectively, with mean DMFT
      (SD) values of 0.07 (0.37), 0.18 (0.62), 0.37 (0.90) and 0.55 (1.09)
      respectively. All outcomes were significantly greater in schoolchildren living in
      rural areas compared with those living in urban areas, and these differences were
      more pronounced in the permanent dentition of the older groups. Of particular
      note, there was a SiC Index (DMFT) of 2.22 for the 9-year-old children living in
      rural areas. CONCLUSION: This survey initially reports the dental caries
      prevalence in a very large sample of Italian schoolchildren and shows that the
      WHO global goal for 2000 has been largely achieved in 6-year-old children,
      although more efforts are needed to reach the new global goal for 2015. The large
      differences in caries prevalence between different areas (rural and urban) and
      their behaviour related to the age group of the samples constitute useful
      findings if prevention programs are to be established in Italy.

PMID- 16961030
TI  - Caries distribution in the dentition and significant caries index in Swedish 4
      year-old children 1980-2002.
AB  - PURPOSE: To analyse possible changes in the severity and distribution of dental
      caries within the dentition in five groups of 4-year-old children examined with
      the same methods and criteria between 1980 and 2002. MATERIALS AND METHODS: The
      material consisted of retrospective caries recordings from cross-sectional
      studies performed in 1980, 1987, 1992, 1997 and 2002 in Umea, Sweden. The
      distribution of dmfs within the dentition was analysed in the whole groups and in
      one third of each group with the highest dmfs-values (mSiC-index). RESULTS: When
      comparing the whole groups, no statistically significant changes were found over
      the years concerning total dmfs, or dmfs in molars and canines or in occlusal
      surfaces (p > 0.05). There was a significant increase in dmfs-values in incisors
      observed between 1980 and 1987, while a similar reduction was observed between
      1987 and 1992 (p < 0.05). When comparing subgroups constituting 33% of those with
      the highest dmfs-values for all teeth in each group, the mean values of dmfs for
      all teeth was higher in 2002 than in 1997 (6.0 compared with 5.3), but the rank
      sum test of dmfs-values displayed a non-significant difference (p > 0.05). There
      was, however, a statistically significant increase in the dmfs-values for molars
      and canines between 1997 and 2002 (p < 0.05). Between 1987 and 1992, a
      statistically significant decrease in dmfs-values in incisors (p < 0.01) was
      found, while the opposite trend occurred between 1992 and 1997 (p < 0.05).
      CONCLUSION: By analysing caries distribution within the dentition and in
      subgroups, trends can be detected over time that otherwise are obscured. The
      findings should be considered in future epidemiological studies, as even
      significant changes could be overlooked and disregarded.

PMID- 16961032
TI  - Important messages for state leaders.

PMID- 16961031
TI  - Risk indicators for a reduced marginal bone level in the individual.
AB  - PURPOSE: The aim of this study was to assess risk indicators for reduced marginal
      bone level in the individual, with emphasis on apical periodontitis. MATERIALS
      AND METHODS: Six hundred and sixteen randomly selected Danish adults (304 women
      and 312 men), mean age of 42 years, underwent a full-mouth radiographic survey.
      The marginal bone level was measured from the cemento-enamel junction to the
      marginal bone. The measurements were performed at the mesial (Am) and distal (Ad)
      aspect of the tooth. The marginal bone level for each individual was calculated:
      Aind = sigma Ateeth/nteeth, and Aind > or =4 mm was considered as reduced
      marginal bone level. The periapical status was assessed by the periapical index
      (PAI), which was dichotomised (healthy = PAI scores 1 and 2, and diseased = PAI
      scores 3, 4 and 5). Coronal restorations (crowns, fillings and inlays) and
      smoking status were also recorded. All variables were analysed in a logistic
      regression model with reduced marginal bone level as the outcome. RESULTS: The
      impact of age (odds ratio (OR) = 3.3), smoking (OR = 10.5) and apical
      periodontitis (OR = 4.7) on reduced marginal bone level was statistically
      significant (p < 0.01). CONCLUSIONS: Not surprisingly, this study showed that
      smoking and older age were risk indicators for having reduced marginal bone level
      > or =4 mm. Even when adjusted for these factors, individuals with > or =1 tooth
      with apical periodontitis were five times more at risk of having a reduced
      marginal bone level than those with no periapical infection.

PMID- 16961033
TI  - SAMHSA at the end of the Curie years. Interview by Michael J Stoil.

PMID- 16961034
TI  - Factoring in structure.

PMID- 16961035
TI  - Aiming to stimulate better outcomes.

PMID- 16961036
TI  - A new way to deliver psychiatric meds.

PMID- 16961037
TI  - Out of jail and into treatment.

PMID- 16961038
TI  - Calling for help.

PMID- 16961039
TI  - Ohio's new tool for data analysis.

PMID- 16961040
TI  - Early plan redesigns raise concerns.

PMID- 16961041
TI  - A new player on the scene.

PMID- 16961042
TI  - Working toward a better future.

PMID- 16961043
TI  - We are different.

PMID- 16961044
TI  - Optimizing adherence to treatment in patients with schizophrenia.

PMID- 16961045
TI  - The realities of the EHR revolution.

PMID- 16961046
TI  - In a crisis, first stop, look, and listen.

PMID- 16961047
TI  - Treatment of type 2 diabetes. Use of fixed-dose oral combinations.

PMID- 16961048
TI  - Treatment of type 2 diabetes. The addition of injection therapy.

PMID- 16961049
TI  - Peripheral arterial disease. A marker of morbidity and mortality.
AB  - Peripheral arterial disease of the lower extremities is a common manifestation of
      the atherosclerotic process. A heightened awareness of symptomatic and
      asymptomatic disease, as well as screening of at-risk patients, is imperative
      because of the increased risk of cardiovascular disease, cerebrovascular disease,
      and even death. This article describes the various symptoms, diagnostic tests,
      and therapies for this common, underdiagnosed, undertreated disease.

PMID- 16961050
TI  - Diagnosis and management of chronic hepatitis B in the primary care setting.
AB  - Chronic hepatitis B is a complex disease for which there are an increasing number
      of approved treatment options. Clinicians who strive to keep up to date on the
      diagnosis and treatment of hepatitis B will be in the best position to meet the
      challenge of managing patients with this serious infection.

PMID- 16961051
TI  - The clinical implications and management of concomitant hypertension and
      dyslipidemia.
AB  - Hypertension and dyslipidemia often coexist, increasing the risk of
      cardiovascular disease. Evidence suggesting that concomitant hypertension and
      dyslipidemia are compelling candidates for a unified approach to treating
      cardiovascular risk is reviewed in this article. The authors also discuss
      important new findings documenting the need for, and benefits of, a more
      integrated approach to treating this dangerous duo.

PMID- 16961052
TI  - Identification and treatment of alcohol use disorders in the perioperative
      period.
AB  - Patients with alcohol use disorders who undergo surgery face added risks and
      longer recovery time. Identification of such patients may reduce these risks,
      allow physicians to increase awareness of surgical requirements, and minimize
      postoperative complications. This article defines the alcohol problems
      encountered, describes preoperative screening tests and treatments, and discusses
      postoperative assessment and management of complications such as alcohol
      withdrawal syndrome.

PMID- 16961053
TI  - Genomic profiling in clinical oncology. The predictive value of genomic
      information in cancer management.
AB  - Genomic profiling is a significant addition to the clinician's armamentarium,
      enabling more specific diagnosis and targeted treatment of a wide range of
      diseases, including cancer. Although not yet widely used in a clinical setting,
      the new technology is providing detailed information about the particular genes
      expressed in malignant tissues. The predictive value of this information has been
      demonstrated in small clinical trials. The results of these and other
      groundbreaking studies are briefly reviewed.

PMID- 16961054
TI  - When back pain is not benign. A concise guide to differential diagnosis.
AB  - When back pain does not improve over time with standard treatment measures, there
      is often the fear that a serious but unrecognized underlying condition may be to
      blame. Proper evaluation to determine the cause of the back pain can ease the
      patient's mind and guide rehabilitation. In this article, Drs Siemionow and
      McLain discuss the characteristic signs and symptoms of the most common serious
      causes of unremitting back pain, as well as the appropriate methods to establish
      a diagnosis.

PMID- 16961055
TI  - Radioiodine imaging in the primary care of thyroid disease.
AB  - There are few indications for ordering a RAIU or a thyroid scan in a primary care
      setting. In suspected hyperthyroidism, a sensitive thyrotropin assay should be
      the initial test ordered. If the thyrotropin level is low or suppressed, and the
      diagnosis of thyroiditis vs Graves' hyperthyroidism is not clear, a RAIU test is
      appropriate. In the case of a euthyroid nodular goiter, fine-needle aspiration is
      the most accurate initial test to evaluate for malignancy. The primary indication
      for a scan in the case of a euthyroid nodular goiter is a low or suppressed
      thyrotropin level, because malignancy is rare in a hot nodule. If thyroid cancer
      or congenital hypothyroidism is encountered, referral to an endocrinologist is
      probably the most expedient and cost-effective way to proceed.

PMID- 16961056
TI  - Time to move. As various market and policy forces change, providers are
      gravitating to EMR environments.

PMID- 16961057
TI  - Vitreous opacities in one eye of an asymptomatic patient. Asteroid hyalosis.

PMID- 16961058
TI  - Large abdominal mass in an elderly man. Sclerosing mesenteritis.

PMID- 16961059
TI  - Is glucosamine MSM effective for osteoarthritis?

PMID- 16961060
TI  - How to work up terminal orgasmic hematospermia?

PMID- 16961061
TI  - Postgraduate Medicine patient notes: putting together a home first-aid kit.

PMID- 16961062
TI  - Affinity of corpora amylacea for oligonucleotides: sequence dependency and
      proteinaceous binding motif.
AB  - Corpora amylacea (CA) have an affinity to nucleic acids as shown by in situ
      hybridization experiments. However, little is known about the specificity of this
      interaction, as well as the mechanism involved. We investigated the ability of
      different probes of digoxigenin-labeled oligonucleotides corresponding to some
      specific neuronal receptors, both sense and antisense, to bind to CA from human
      autopsy brain tissue. The bound nucleotides were detected with antidigoxigenin
      antibody and the signal was further amplified using the tyramide signal
      amplification system. The affinity of binding varies with the sequence of
      nucleotides. The most intense signal is produced by the adenosine-2A receptor
      antisense probe and the least intense signal is produced by the N-methyl-D
      aspartate receptor sense probe. The affinity of binding for the same probe does
      not depend on the localization of CA in the central nervous system. Complete
      staining loss by proteinase K pretreatment in higher concentrations shows that
      the binding motif is partially proteinaceous. The circumferential but not the
      punctate internal staining is diminished by mild amylglucosidase pretreatment,
      suggesting a process of progressive apposition and condensation.

PMID- 16961063
TI  - Heterogeneous hyperactivity and distribution of ischemic lesions after focal
      cerebral ischemia in Mongolian gerbils.
AB  - Various types of poststroke hyperactivity exist in humans, but studies of each
      mechanism using animal models are scarce. We aimed to analyze the heterogeneity
      of postischemic hyperlocomotion and to identify the ischemic lesions responsible
      for postischemic hyperlocomotion in rodent models of focal ischemia. Mongolian
      gerbils underwent right common carotid artery occlusion (CCAO) for 10 or 20 min.
      At 24 h, 2 days, and 7 days postischemia, we performed quantitative and
      qualitative locomotor analysis and correlated these results with the extent of
      ischemic lesions. Intermittent explosive hyperlocomotion was induced transiently
      in a 10-min CCAO group at 24 h after ischemia and continual unexplosive
      hyperlocomotion persisted for 7 days in the 20-min CCAO animals. Selective
      neuronal death, confined to the hippocampal cornu ammonis 1 (CA1), was observed
      in the 10-min CCAO group and widespread cortical and basal ganglia infarction was
      observed in the 20-min CCAO group. Amyloid precursor protein was transiently
      observed in the hippocampus at 24 h postischemia in the 10-min CCAO animals,
      while it was widely distributed over the ischemic regions throughout the 7 days
      postischemia in the 20-min CCAO animals. Incidence maps and correlation analysis
      revealed hippocampal neuronal death of the CA1 sector and widespread hemispheric
      infarction, including the cortex, as the region responsible for the 10-min and 20
      min CCAO-induced hyperactivity, respectively. Two distinct types of locomotor
      hyperactivity were observed that varied with regard to the distribution of the
      ischemic lesion, that is, hippocampal neuronal death and widespread infarction
      involving the cortex. These two types of locomotor hyperactivity appear to be
      models of the different types of poststroke hyperactivity seen in stroke
      patients.

PMID- 16961064
TI  - Vascular complications in dementia with Lewy bodies: a postmortem study.
AB  - The effects of cerebrovascular lesions on DLB are not yet fully understood,
      whereas the development of Alzheimer's disease (AD) is known to be associated
      with cerebrovascular lesions. In this study, we investigated the frequency of
      concomitant cerebrovascular pathologies in autopsy-proven DLB cases (n = 25) in
      comparison with AD cases (n= 63). We also investigated the correlation between
      cerebrovascular pathologies and the clinical features of DLB cases. On gross
      inspection, five cases of DLB and seven cases of AD were complicated by cerebral
      hemorrhages and the difference was significant; most of the lesions in DLB were
      subdural hemorrhages, possibly related to trauma. Nine cases of DLB and 25 cases
      of AD had grossly identified infarctions, but no significant difference was
      observed. Three cases of DLB and four cases of AD had concomitant hemorrhages,
      while 10 cases of DLB and 43 cases of AD had infarcts on microscopic inspection.
      There was a significant difference in the frequency of microscopic infarcts
      between DLB and AD, whereas no significant difference was noted in the frequency
      of microscopic hemorrhages. In DLB cases without vascular complications, memory
      disturbance was common as the initial symptom, while parkinsonism was more common
      in those with vascular complications. However, no significant difference was
      observed between DLB cases with and without vascular complications with respect
      to the frequency of individual clinical symptoms over the whole clinical course.
      These findings suggest that grossly identified hemorrhages are more common in DLB
      because of trauma, while microinfarcts are less common in DLB than AD, although
      the reason remains unclear. Such vascular complications might affect the clinical
      manifestations, in particular, the initial symptom, of DLB.

PMID- 16961065
TI  - Role of endoglin and transforming growth factor-beta in progressive white matter
      damage after an ischemic stroke.
AB  - We morphologically examined human brains several years after a territorial
      ischemic stroke to assess the development of progressing white matter damage and
      its pathomechanisms. Our investigations focused on the role of TGF-beta, one of
      the factors whose expression increases after tissue damage, and its receptor
      endoglin in the propagation of postischemic injury. Examination of the white
      matter adjacent to the postapoplectic cavity revealed structural changes in the
      capillary vessels, disturbed microcirculation, and deep endothelial cell damage
      with DNA fragmentation in the TUNEL reaction. Many oligodendrocytes also revealed
      DNA damage and an increased expression of caspase-3. In the rarefied white
      matter, the microvessel immune reaction to TGF-beta was diminished while the
      expression of endoglin was heterogeneous: absent in some capillaries but
      increased in others in comparison to the vessels located more peripherally from
      the cavity and in the control material. We conclude that endoglin and TGF-beta
      can be involved in the development of the microangiopathy responsible for the
      propagation of postischemic white matter injury in humans. We suggest that
      disturbances in endoglin expression can influence TGF-beta signaling and,
      consequently, vessel structure and function. Pronounced endoglin expression can
      lead to decreased vessel wall integrity while a lack of the constitutively
      expressed protein is probably a mirror of deep vessel damage.

PMID- 16961066
TI  - Interleukin-18 and transforming growth factor-beta 1 plasma levels in Alzheimer's
      disease and vascular dementia.
AB  - Inflammation has been involved in the development of dementia in cerebrovascular
      diseases. To investigate the cellular activation of the peripheral immune system
      in patients with Alzheimer's disease (AD) and vascular dementia (VaD), we
      determined the presence of IL-18 and TGF-beta1 in the plasma by using ELISA. The
      levels of IL-18 and TGF-beta1 were significantly elevated in patients with AD and
      VaD compared to non-demented, age-matched subjects. We found an inverse
      correlation between the levels of IL-18 and TGF-beta1 in AD patients. In VaD
      patients, the correlation between IL-18 and TGF-beta1 reached a borderline
      positive value. Whereas, in the non-demented, age-matched subjects, a positive
      correlation between IL-18 and TGF-beta1 levels was observed. These findings
      indicate that IL-18 and TGF-beta1 elevation is associated with AD and VaD
      patients, confirming that the immune system might exert a remarkable role in the
      development and progression of neurodegenerative disorders. Moreover, as
      different modifications were detected in the patients affected by AD and VaD, we
      propose that IL-18 and TGF-beta1 plasma levels might represent possible
      differential biomarkers.

PMID- 16961067
TI  - Autopsy case of Creutzfeldt-Jakob disease with Met/Val heterozygosity at codon
      129 and type 1 protease-resistant prion protein presenting some florid-type
      plaques and many Kuru plaques in the cerebellum.
AB  - We report an atypical case of CJD. The clinical course was similar to a classic
      CJD phenotype, but histopathological study revealed several florid-type plaques
      in the amygdale and abundant Kuru plaques in the cerebellum that are atypical of
      classic CJD. Molecular analysis showed methionine/valine heterozygosity at codon
      129 and no pathogenic mutation in the coding region of the prion protein gene.
      Western immunoblots revealed type 1 protease-resistant prion protein (PrPres),
      and a ration analysis of PrPres showed a high ratio of the diglycosylated form
      and a low ratio of the non-glycosylated form. Our case could not be precisely
      classified in any of Parchi's six variants. It suggests the existence of some
      factors that determine the phenotypic variability other than the codon 129
      genotypes in the PrP gene or the physicochemical properties of PrPres.

PMID- 16961068
TI  - Desmoplastic infantile ganglioglioma with calcification.
AB  - Desmoplastic infantile gangliogliomas (DIGs) are rare intracranial, cystic
      tumors, usually detected within the first 2 years of life. Histologically, these
      tumors are characterized by intense desmoplasia and a divergent astrocytic and
      neuronal differentiation. Less than 60 well-documented cases of this extremely
      rare tumor are reported in the literature. We present the case of a 10-month-old
      male child presenting with a large, cystic, intracranial lesion and having the
      characteristic histological features of a DIG. In addition, the lesion also
      showed focal areas of calcification within the tumor, not usually considered a
      feature of this entity. The present case extends the reported spectrum of this
      rare entity and describes the unusual occurrence of calcification within the
      lesion.

PMID- 16961069
TI  - Chronic superior sagittal sinus thrombosis with phlebosclerotic changes of the
      subarachnoid and intracerebral veins.
AB  - An autopsy case of chronic thrombotic occlusion of the superior sagittal sinus
      (SSS) with an unusually protracted clinical course is reported. The patient was
      an 84-year-old man without any predisposing conditions for thrombosis. The
      clinical features were atypical and were characterized by recurrent cerebral
      subcortical hemorrhages. The autopsy revealed a large, organized thrombus in the
      SSS and extensive hemorrhagic infarction of the bilateral parasagittal region of
      the cerebral hemispheres. The hemorrhagic infarction was comprised of the
      aggregation of numerous minute foci of coagulation necrosis associated with
      petechial hemorrhages. Marked phlebosclerotic changes were observed in the
      subarachnoid and intracerebral veins, which were considered to be reactive
      changes of the venous walls against a persistent elevation in peripheral venous
      pressure caused by thrombosis of the SSS.

PMID- 16961070
TI  - Acute motor and sensory neuronopathy associated with small-cell lung cancer: a
      clinicopathological study.
AB  - A 48-year-old Chinese woman developed ascending motor paralysis while visiting
      Japan, leading to tetraplegia and respiratory failure over 2 weeks. The patient's
      course was complicated by anoxic encephalopathy. Nerve conduction studies
      revealed a severely decreased amplitude of compound muscle action potentials and
      a sural nerve biopsy specimen showed findings consistent with axonal-form
      Guillain-Barr6 syndrome. An autopsy, excluding the brain, demonstrated small-cell
      lung cancer that was not detected clinically, axonal-dominant degeneration in the
      nerve roots and distal peripheral nerves, and the loss of both myelin and axons
      in the dorsal spinal column. The spinal anterior horn cells were severely
      decreased and were accompanied by astrocytic reaction in all spinal segments with
      lymphocytic infiltration. A limited examination of the dorsal root ganglia did
      not show Nageotte nodules, but the infiltration of T cells was observed. Although
      the clinical course mimicked axonal-form Guillain-Barre syndrome, the autopsy
      demonstrated both sensory and motor neuronal involvement, as well as small-cell
      lung cancer. Although anti-Hu and antiganglioside antibodies were negative in the
      patient's serum, the para-neoplastic mechanism might have damaged the anterior
      horn and dorsal root ganglia cells, which subsequently led to secondary axonal
      degeneration. There has been a report on a case of paraneoplastic subacute motor
      neuronopathy, but the acute course described here has not been reported before.

PMID- 16961071
TI  - Cellular pathology in multiple system atrophy.
AB  - Multiple system atrophy (MSA) is a sporadic, adult-onset neurodegenerative
      disease, which is characterized by striatonigral degeneration,
      olivopontocerebellar atrophy, and preganglionic autonomic lesions in any
      combination. The histological hallmark is the presence of argyrophilic fibrillary
      inclusions in the oligodendrocytes, referred to as glial cytoplasmic inclusions
      (GCIs). Fibrillary inclusions are also found in the neuronal somata, axons, and
      nucleus. Neuronal cytoplasmic inclusions are frequently found in the pontine and
      inferior olivary nuclei. Since the discovery of alpha-synuclein as a major
      component of glial and neuronal inclusions in MSA, two neurodegenerative
      processes have been considered in this disease: one is due to the widespread
      occurrence of GCIs associated with oligodendroglia-myelin degeneration
      (oligodendrogliopathy) in the central nervous system, and the other is due to the
      filamentous aggregation of alpha-synuclein in the neurons in several brain
      regions. These two degenerative processes might synergistically cause neuronal
      depletion in MSA.

PMID- 16961072
TI  - Polyglutamine disease: recent advances in the neuropathology of dentatorubral
      pallidoluysian atrophy.
AB  - Polyglutamine diseases are hereditary neurodegenerative disorders that are caused
      by the expansion of a CAG repeat in the causative genes. They comprise at least
      nine disorders, including DRPLA, HD, and Machado-Joseph disease. Initially, the
      discovery of neuronal intranuclear inclusions (NIIs) in human brains and in a
      murine model of HD provided a plausible hypothesis that the expression of
      expanded polyglutamine stretches leads to NII formation, resulting in neuronal
      cell death in selective brain regions characteristic to each disease. Recent
      studies, however, suggest that nuclear dysfunction, especially transcriptional
      abnormalities caused by the diffuse intranuclear accumulation of mutant proteins,
      plays a pivotal role in the development and progression of clinical symptoms.
      Polyglutamine diseases have a similarity with neuronal storage disease, and this
      pathological process might become a target for the establishment of an effective
      therapy for these diseases.

PMID- 16961073
TI  - On autosomal dominant cerebellar ataxia (ADCA) other than polyglutamine diseases,
      with special reference to chromosome 16q22.1-linked ADCA.
AB  - Autosomal dominant cerebellar ataxia (ADCA) is a group of heterogeneous
      conditions. More than 20 genes or gene loci have been identified that are
      responsible for ADCA. Although expansions of the trinucleotide (CAG) repeat that
      encode polyglutamine are known to cause some forms of ADCA, growing knowledge
      about the genetic basis of ADCA indicates that many subtypes of ADCA are caused
      by mutations other than the CAG repeat/polyglutamine expansion. In this paper, we
      review ADCA caused by mutations other than polyglutamine expansions (i.e. "non
      polyglutamine diseases"). We also describe the neuropathology of chromosome
      16q22.1-linked ADCA, which appears to be the most common non-polyglutamine
      disease in Japan. What we find to be characteristic on the chromosome 16q22.1
      linked ADCA brain is the presence of atrophic Purkinje cells surrounded by the
      formation of amorphous material, the latter composed of the Purkinje cell
      dendrites stemming from the cell bodies, the presynaptic terminals innervated by
      certain neurons, and the astroglial processes. Such neuropathological findings
      seem to be unique for this disease.

PMID- 16961074
TI  - Spinocerebellar ataxia with ocular motor apraxia and DNA repair.
AB  - At least four disorders, ataxia telangiectasia (AT), an ataxia-telangiectasia
      like disorder, early-onset ataxia with ocular motor apraxia and hypoalbuminemia
      (EAOH)/ ataxia with oculomotor apraxia type 1 (AOA1), and ataxia with oculomotor
      apraxia type 2, are accompanied by ocular motor apraxia (OMA), which is an
      impairment of saccadic eye movement initiation. The characteristic pathological
      findings of EAOH/AOA1 and AT are a severe loss of Purkinje cells, severe myelin
      pallor of the posterior columns, and moderate neuronal loss in the dorsal root
      ganglia and anterior horn. Purkinje cells stimulate the fastigial nucleus and
      suppress omnipause neurons to initiate saccadic eye movement. The selective loss
      of Purkinje cells might cause OMA and disturb the cancellation of the vestibulo
      ocular reflex. These disorders have the following common clinical features:
      ataxia, involuntary movements, and peripheral neuronopathy. In addition, the
      causative genes for these disorders are associated with the DNA/RNA quality
      control system. The impairment of DNA/ RNA integrity results in selective
      neuronal loss in these recessive-inherited ataxias.

PMID- 16961075
TI  - Autosomal recessive spastic ataxia of Charlevoix-Saguenay.
AB  - Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) was originally
      found among the inhabitants of the Charlevoix-Saguenay region of Quebec, Canada.
      This disease is characterized by early-onset ataxia, spasticity, peripheral
      neuropathy, finger and foot deformities, and hypermyelination of the retinal
      nerve fibers. The mentality of the patients is usually intact. The principal
      neuropathology comprises atrophy of the upper vermis and the loss of Purkinje
      cells in the cerebellum. Although the lateral corticospinal tracts are
      degenerated, the precentral gyrus, dentate nucleus, and inferior olivary nucleus
      are intact. Recently, the gene responsible for ARSACS was determined to encode
      the sacsin protein in the Quebec patients. In 2004, we first reported a Japanese
      family with a SACS mutation. So far, we have identified the SACS mutations in a
      total of five Japanese families with ARSACS and analyzed the clinical features of
      eight patients. Interestingly, we found some atypical clinical features in the
      Japanese patients: a slightly later onset than that of the Quebec patients, an
      absence of myelinated retinal fibers, intellectual impairment, and a lack of
      spasticity. To date, there have been descriptions of non-Quebec patients with
      SACS mutations in Japan, Italy, Tunisia, and Turkey. Hereafter, as more SACS
      mutations are identified, the clinical spectrum of the "sacsinopathies" could
      expand.

PMID- 16961076
TI  - Predominant motor symptoms in a 74-year-old man with a small elongation in the
      spinocerebellar atrophy type 1 gene.
AB  - The patient was a 74-year-old man who developed gait and bulbar disturbances,
      which progressed for several years. His mother and a sister complained of a
      similar disturbance. On admission, generalized muscle atrophy and weakness were
      prominent, especially in the distal portions of the legs, with bulbar
      involvement. The patellar tendon reflexes were retained and the Achilles tendon
      reflexes were decreased with a positive right Babinski's sign. The ocular
      movements were restricted in vertical directions and, to a lesser extent, in
      horizontal directions. Sensory disturbance, ataxia, and extrapyramidal signs were
      not apparent on admission. A needle electromyogram demonstrated neurogenic
      changes. The laboratory examination was normal except for elevated blood glucose
      (320 mg/dL) and creatine kinase (1760 U/L). His general condition deteriorated so
      rapidly that intractable respiratory distress due to pneumonia led to a fatal
      outcome. The clinical diagnosis was motor neuron disease, although a familial
      background and a disturbance in ocular movements might have suggested other
      possibilities.

PMID- 16961077
TI  - Pacinian corpuscle in a lymph node.

PMID- 16961078
TI  - Failure modes of spinal cord stimulation hardware.
AB  - OBJECT: Epidural spinal cord stimulation (SCS) is effective at treating
      refractory pain. The failure modes of the implanted hardware, however, have not
      been well studied. A better understanding of this could aid in improving the
      current procedure or designing future devices. METHODS: The authors reviewed
      electronic charts and operative reports of 289 patients who had undergone SCS
      implantation between 1998 and 2002 at the Cleveland Clinic Foundation. Data were
      collected on demographics, type of hardware, date of implantation procedure,
      indication for treatment, time to failure, and failure mode. Data were then
      analyzed to identify significant differences. A total of 577 procedures were
      performed, 43.5% of which involved revision or removal of SCS hardware. The most
      common indication was complex regional pain syndrome 1, and this was followed by
      failed-back surgery syndrome. The median number of procedures per patient was
      two. Approximately 80% of all leads were the percutaneous type. The majority
      (62%) of leads were placed in the thoracic region, and 33.5% of all leads
      required revision. Poor pain relief coverage was the most common indication for
      revision. Surgically implanted leads broke twice as often as percutaneous leads.
      In 46% of the patients, hardware revision was required, and multiple revisions
      were necessary in 22.5%. Three-way ANOVA revealed significant differences in
      failure mode rates according to location (cervical compared with thoracic, p =
      0.037) and failure modes (p = 0.019). Laminotomy leads tended to break and
      migrate sooner than percutaneous leads. Thoracic leads became infected sooner
      than cervical leads. CONCLUSIONS: The results of this analysis of SCS hardware
      failures may be used as a basis for refining surgical technique and designing the
      next generation of SCS hardware.

PMID- 16961079
TI  - Complications of spinal cord stimulation, suggestions to improve outcome, and
      financial impact.
AB  - OBJECT: The long-term success of spinal cord stimulation is impeded by the high
      incidence of adverse events. The cost of complications to the healthcare budget
      is influenced by the time course needed to reverse the effect, and by the type of
      corrective measures required. Understanding the mechanism of complications and
      reducing them can improve the overall success rate and the cost factor. METHODS:
      The authors performed a retrospective analysis of data obtained in 160 patients
      treated during a 10-year period. For each category of complication, the level of
      healthcare resource use was assessed for each case and a unit cost was applied.
      The total cost of each complication was determined by summing across healthcare
      resource headings. All cost calculations were performed in Canadian dollars at
      2005 prices. To understand the mechanics of various hardware-related
      complications and how to avoid them, the authors have utilized the results of
      bench tests conducted at Medtronic, Inc. Fifty-one adverse events occurred in 42
      of the 160 patients. The complications were classified as either hardware related
      (39 events) or biological (12 events). The mean cost of complications during the
      10-year study period was dollar 7092 (range dollar 130 - dollar 22,406).
      CONCLUSIONS: Complications not only disrupt the effect of pain control but also
      pose an added expense to the already high cost of therapy. It is possible to
      reduce the complication rate, and thus improve the long-term success rate, by
      following the suggestions made in this paper, which are supported by the
      biomechanics of the human body and the implanted material.

PMID- 16961080
TI  - Cost-utility analysis of routine neurosurgical spinal surgery.
AB  - OBJECT: Cost-utility analysis is currently the preferred method with which to
      compare the cost-effectiveness of various interventions. The authors conducted a
      study to establish the cost-utility results of routine neurosurgery-based spinal
      interventions by examining patient-derived values. METHODS: Two hundred seventy
      patients undergoing surgery for cervical or lumbar radicular pain filled in the
      15-dimensional health-related quality of life (HRQOL) questionnaire before and 3
      months after surgery. Quality-adjusted life years (QALYs) were calculated using
      the utility data and the expected remaining life years of the patients. The mean
      HRQOL score (scale, 0-1) increased after cervical surgery (169 patients, mean age
      52 years, 40% women) from 0.81 +/- 0.11 preoperatively, to 0.85 +/- 0.11 at 3
      months, and after lumbar surgery (101 patients, mean age 54 years, 59% women)
      from 0.79 +/- 0.10 preoperatively, to 0.85 +/- 0.12 at 3 months (p < 0.001). Of
      the 15 dimensions of health, improvement in the following was documented in both
      groups: sleeping, usual activities, discomfort and symptoms, depression,
      distress, vitality, and sexual activity (p < 0.05). The cost per QALY gained was
      Euro 2774 and 1738 for cervical and lumbar operations, respectively. In cases in
      which surgery was delayed the cost per QALY was doubled. CONCLUSIONS: Spinal
      surgery led to a statistically significant and clinically important improvement
      in HRQOL. The cost per QALY gained was reasonable, less than half of that
      observed, for example, for hip replacement surgery or angioplasty treatment of
      coronary artery disease; however, a prolonged delay in surgical intervention led
      to an approximate doubling of the cost per QALY gained by the treatment.

PMID- 16961081
TI  - Detected and overlooked cervical spine injury in comatose victims of trauma:
      report from the Pennsylvania Trauma Outcomes Study.
AB  - OBJECT: This study was undertaken to determine whether a clinically useful rule
      could be formulated for identifying the presence of traumatic brain injury (TBI)
      in patients who are at exceptionally low risk of cervical spine injury. METHODS:
      The Pennsylvania Trauma Outcomes Study database was searched for cases of TBI in
      which the admission Glasgow Coma Scale (GCS) score was less than or equal to 8.
      Cases of cervical injury were identified based on diagnostic codes. Associations
      between cervical injury and various clinical variables were tested using chi
      square analysis. The probability of cervical injury was modeled using logistic
      regression. Decision tree models were constructed. Statistical determinants of
      overlooked cervical injury were examined. The prevalence of cervical injury among
      41,142 cases of TBI was 8%. Mechanism of injury, thoracolumbosacral (TLS)
      fracture, age, limb fracture, admission GCS score, hypotension, and facial
      fracture were associated with cervical injury and were incorporated into the
      following logistic regression model: probability = 1/(1 + exp[4.248 - 0.417 X
      mechanism -0.264 X age - 0.678 X TLS - 0.299 X limb - 0.218 X GCS - 0.231 X
      hypotension - 0.157 X facial]). The results of applying this model provided a
      rule for cervical spine clearance applicable to 28% of the cases with a negative
      predictive value (NPV) of 97.0%. Decision tree analysis yielded a rule applicable
      to 24% of the cases with an NPV of 98.2%. The prevalence of overlooked cervical
      injury in all individuals with severe TBI was 0.3%; the prevalence of overlooked
      cervical injury in patients with cervical injury was 3.9%. Overlooked cervical
      injury was less common in patients with associated TLS fractures (odds ratio
      0.453, 95% confidence interval 0.245-0.837). CONCLUSIONS: This analysis
      identified no acceptable rule to justify relaxing vigilance in the search for
      cervical injury in patients with severe TBI. Provider vigilance and consequent
      rates of overlooked cervical injury can be affected by environmental cues and
      presumably by other behavioral and organizational factors.

PMID- 16961082
TI  - Development and psychometric properties of the Vertebral Compression Fracture
      Pain and Functional Disability Questionnaire.
AB  - OBJECT: Vertebral compression fractures (VCFs) result in severe and disabling
      pain, diminished quality of life, and substantial medical costs. There exists no
      standard instrument with which to measure pain and functional status before and
      after treatment of VCFs. METHODS: A questionnaire was specifically developed to
      assess pain and disability in patients with VCFs before and after undergoing
      percutaneous polymethylmethacrylate-augmented vertebroplasty. The first section
      of the baseline questionnaire (before treatment) contains 11 items that address
      the patient's previous and current levels of back pain and distress. The second
      section of the baseline questionnaire lists 24 activities of daily living (ADLs),
      each measured on a four-point scale ranging from "able to do without pain" to
      "cannot do because of pain." The follow-up questionnaire (after treatment) is
      similar in format. Among 72 vertebroplasty-treated patients, the internal
      consistency reliability of the 24 ADLs ranged from 0.87 to 0.98, with similar
      results observed before and after treatment. Correlations of 0.29 to 0.72 were
      observed among the 24 ADLs and the internal measures of pain and distress
      measured on both visual analog and adjectival scales. Similar correlations (range
      0.35-0.63) were observed between the questionnaire and 10 dimensions of the
      Oswestry Disability Index's low-back pain questionnaire, an external instrument
      used to assess criterion-referenced validity. Evidence in support of the validity
      of the questionnaire was present before and after treatment. CONCLUSIONS: The
      Vertebral Compression Fracture Pain and Functional Disability Questionnaire
      appears to be a reliable and valid instrument for assessing back pain and
      functional ability in patients before and after treatment for VCFs.

PMID- 16961083
TI  - Predictive factors for dural tear and cerebrospinal fluid leakage in patients
      undergoing lumbar surgery.
AB  - OBJECT: A dural tear resulting in a cerebrospinal fluid (CSF) leak is a well
      known risk of lumbar spinal procedures. The authors hypothesized that the
      incidence of CSF leakage is higher in cases involving repeated operations and
      those in which the surgeon performing the surgery is less experienced; however,
      they postulated that the overall outcome of the patient would not be adversely
      affected by a dural tear. METHODS: An institutional review board-approved
      protocol at Louisiana State University Health Sciences Center, Shreveport, was
      initiated in August 2003 to allow prospective comparison of data obtained in
      patients in whom a CSF leak occurred (Group A) and those in whom no CSF leak
      occurred (Group B) during lumbar surgery. Basic demographic information,
      descriptive findings regarding the tear, history of other surgeries, hospital
      length of stay (LOS), and immediate disposition at the time of discharge were
      compared between the two groups. Seventy-seven patients were eligible for this
      study. One patient refused to participate. In 12 (15.8%) of 76 patients CSF
      leakage developed. In three patients the presence of a tear was questioned, and
      the patients were clinically treated as if a tear were present. The patients in
      Group A were older than those in Group B (59.8 +/- 16.9 and 49.4 +/- 13.6 years
      of age, respectively; p = 0.02, Fisher exact test). In terms of those with a
      history of surgery, there was no significant difference between patients with and
      patients without a CSF leak (three [25%] of 12 patients [Group A] compared with
      28 [43.8%] of 64 patients [Group B]; p = 0.34, two-sample t-test). In the 12
      patients with dural tears, nine (75%) were caused by a resident-in-training, and
      the Kerrison punch was the instrument most often being used at the time (55%).
      This is significantly greater than 50% at the 5% level (p = 0.044, binomial
      test). The authors were able to repair the tear primarily with suture in all but
      one patient, whose tear was along the nerve root sleeve. In all cases fibrin glue
      and a muscle/fat graft were used to cover the tear, and all patients were
      assigned to bed rest from 24 to 48 hours after the operation. In Group A one
      patient required rehabilitation at discharge. The LOS in Group A was greater than
      that in Group B (median 5 days compared with 3 days), but no additional
      complication was noted. CONCLUSIONS: The incidence of CSF leakage was 16% in 76
      patients, and there were no other complications. Older patient age and higher
      level of the surgeon's training were factors contributing to the incidence, but
      the history of surgery was not.

PMID- 16961084
TI  - Revision surgery of the lumbar spine: anterior lumbar interbody fusion followed
      by percutaneous pedicle screw fixation.
AB  - OBJECT: The aim of this study was to evaluate the efficacy of anterior lumbar
      interbody fusion (ALIF) augmented by percutaneous pedicle screw fixation (PSF)
      for revision surgery in the lumbar spine and to determine the prognostic factors
      affecting surgical outcomes. METHODS: The population included 54 consecutively
      treated patients in whom revision surgery involving ALIF with PSF was performed
      between 2001 and 2004. There were 22 men and 32 women, whose mean age was 59.5
      years (range 25-78 years). The diagnoses prior to revision ALIF were as follows:
      degenerative disc disease in 25 patients, instability/spondylolisthesis in 15,
      recurrent disc herniation in seven, and pseudarthrosis in seven. The mean follow
      up period was 24 months (range 12-52 months). The mean visual analog scale score
      for back and leg pain decreased, respectively, from 7.8 to 2.3 and 8.0 to 2.3 (p
      < 0.001). The mean Oswestry Disability Index score improved from 70 to 25% (p <
      0.001). Radiological evidence of fusion was noted in 52 of 54 patients. The mean
      preoperative segmental lordosis, whole lumbar lordosis, and sacral tilt were
      15.2, 35.5, and 28.3 degrees, respectively; these values were significantly
      increased to 20.4, 40.7, and 31.4degrees, respectively, after revision surgery (p
      < 0.001). The increase in sacral tilt was positively correlated with improvement
      in back pain (p = 0.028) and functional status (p = 0.025). CONCLUSIONS: The
      results demonstrate that ALIF followed by PSF can be an effective alternative in
      revision surgery of the lumbosacral spine in selected cases. Not only can solid
      fusion be achieved, sagittal alignment can also be restored in the majority of
      patients.

PMID- 16961085
TI  - Repetitive tensile stress to rat caudal vertebrae inducing cartilage formation in
      the spinal ligaments: a possible role of mechanical stress in the development of
      ossification of the spinal ligaments.
AB  - OBJECT: Mechanical stress has been considered one of the important factors in
      ossification of the spinal ligaments. According to previous clinical and in vitro
      studies, the accumulation of tensile stress to these ligaments may be responsible
      for ligament ossification. To elucidate the relationship between such mechanical
      stress and the development of ossification of the spinal ligaments, the authors
      established an animal experimental model in which the in vivo response of the
      spinal ligaments to direct repetitive tensile loading could be observed. METHODS:
      The caudal vertebrae of adult Wistar rats were studied. After creating a novel
      stimulating apparatus, cyclic tensile force was loaded to rat caudal spinal
      ligaments at 10 N in 600 to 1800 cycles per day for up to 2 weeks. The
      morphological responses were then evaluated histologically and
      immunohistochemically. After the loadings, ectopic cartilaginous formations
      surrounded by proliferating round cells were observed near the insertion of the
      spinal ligaments. Several areas of the cartilaginous tissue were accompanied by
      woven bone. Bone morphogenetic protein-2 expression was clearly observed in the
      cytoplasm of the proliferating round cells. The histological features of the rat
      spinal ligaments induced by the tensile loadings resembled those of spinal
      ligament ossification observed in humans. CONCLUSIONS: The findings obtained in
      the present study strongly suggest that repetitive tensile stress to the spinal
      ligaments is one of the important causes of ligament ossification in the spine.

PMID- 16961086
TI  - Spinal cord-fragment interactions following burst fracture: an in vitro model.
AB  - OBJECT: The purpose of the study was to develop an in vitro model of the bone
      fragment and spinal cord interactions that occur during a burst fracture and
      further the understanding of how the velocity of the bone fragment and the status
      of the posterior longitudinal ligament (PLL) affect the deformation of the cord.
      METHODS: An in vitro model was developed such that high-speed video and pressure
      measurements recorded the impact of a simulated bone fragment on sections of
      explanted bovine spinal cord. The model simulated the PLL and the posterior
      elements. The status of the PLL had a significant effect on both the maximum
      occlusion of the spinal cord and the time for occlusion to occur. Raising the
      fragment velocity led to an overall increase in the spinal cord deformation.
      Interestingly the dura mater appeared to have little or no effect on the extent
      of occlusion. CONCLUSIONS: These findings may indicate the importance of the
      dura's interaction with the cerebrospinal fluid in protecting the cord during
      this type of impact.

PMID- 16961087
TI  - Delayed postoperative spinal epidural hematoma causing tetraplegia. Case report.
AB  - The authors describe a case of postoperative spinal epidural hematoma (PSEH) that
      developed in a patient 9 days after he underwent laminoplasty. A PSEH is a rare
      but critical complication of spinal surgery that usually occurs within a few days
      of the procedure. The authors draw attention to the possibility of delayed PSEH
      and its triggering mechanism. In this case, a 59-year-old man with no history of
      bleeding disorder underwent cervical laminoplasty for mild myelopathy. On the 7th
      postoperative day computed tomography demonstrated no abnormal findings in the
      operative field. On the 9th postoperative day, while straining to defecate, the
      patient suddenly felt neck and shoulder pain, and tetraplegia rapidly developed.
      Magnetic resonance imaging demonstrated a huge epidural hematoma. The clot was
      evacuated during emergency revision surgery, during which the arterial bleeding
      from a split muscle wall was confirmed. The postoperative course after the
      revision surgery was uneventful and the patient had none of the previous symptoms
      1 year later. A PSEH causing paralysis can occur even more than a week after
      surgery. The possibility of a delayed-onset PSEH should be kept in mind, and
      prompt diagnosis should be made when a patient presents with paresis or paralysis
      after an operation. The authors recommend advising patients that for a while
      after surgery they avoid strenuous activity.

PMID- 16961088
TI  - Spinal cord compression from traumatic anterior cervical pseudomeningoceles.
      Report of three cases.
AB  - Pseudomeningoceles rarely develop after cervical trauma; in all reported cases
      the lesions have extended outside the spinal canal. The authors report the first
      known cases of anterior cervical pseudomeningoceles contained entirely within the
      spinal canal and causing cord compression and neurological injury. The authors
      retrospectively reviewed the cases of three patients with traumatic cervical
      spine injuries and concomitant compressive anterior pseudomeningoceles. The
      lesion was recognized in the first case when the patient's neurological status
      declined after he sustained a severe atlantoaxial injury; the pseudomeningocele
      was identified intraoperatively and decompressed. After the decompressive
      surgery, the patient's severe tetraparesis partially resolved. In the other two
      patients diagnoses of similar pseudomeningoceles were established by magnetic
      resonance imaging. Both patients were treated conservatively, and their mild to
      moderate hemiparesis due to the pseudomeningocele-induced compression abated. The
      high incidence of anterior cervical pseudomeningoceles seen at the authors'
      institution within a relatively brief period suggests that this lesion is not
      rare. The authors believe that it is important to recognize the compressive
      nature of these lesions and their potential to cause devastating neurological
      injury.

PMID- 16961089
TI  - Correlation of anomalous vascular and osseous anatomy in congenital kyphosis type
      I. Case report.
AB  - Congenital kyphosis Type I results from failure of formation of the vertebral
      body (VB). The clinical course is characterized by progressive deformity and
      neurological dysfunction unless the patient undergoes fusion. It has been
      postulated that failure of VB formation may be secondary to anomalies of the
      segmental arteries arising from the aorta. There is limited clinical evidence in
      the literature, however, to support this hypothesis. The authors report on the
      case of an adult patient with congenital kyphosis Type I in whom spinal
      angiography correlated vascular with vertebral anomalies. This 32-year-old man
      presented with back pain, lower-extremity paresthesias, and incomplete voiding,
      which had progressed over several years. Imaging revealed that the L-1 and L-2
      vertebrae had not fully formed, causing kyphotic deformity such that the anterior
      portion of T-12 nearly articulated with that of L-3; this anomaly produced
      significant mobility in flexion and extension. Magnetic resonance imaging
      revealed distal spinal cord atrophy and signal change on T2-weighted images.
      Spinal angiography showed that the right and left segmental arteries at both L-1
      and L-2 arose from a common trunk from the aorta. This was confirmed during
      subsequent T12-L3 anterior-posterior fusion. Postoperatively the patient
      experienced relief of pain and remained neurologically stable throughout a 3-year
      follow-up period. The presence of corresponding anomalies of the segmental
      arteries and vertebrae in this case of congenital kyphosis Type I indicates that
      a relationship may exist in the genesis of aberrant spinal vertebral and vascular
      structures.

PMID- 16961090
TI  - Three-dimensional ultrasonography navigation in spinal cord tumor surgery.
      Technical note.
AB  - The authors describe the technical application of three-dimensional (3D)
      ultrasonography navigation in spinal cord tumor surgery. The spinal cord is a
      complex neurological structure in which there is the potential for causing
      neurological morbidity during tumor resection. Standard neuronavigation systems
      based on computed tomography or C-arm images are not adapted to tumor surgery in
      the spinal cord. Since 2004 the authors have been using a 3D ultrasonography
      based neuronavigation system. During surgery, two-dimensional ultrasound images
      were acquired and reconstructed into 3D image data to assist in tumor resection.
      The navigation cameras read the position of a patient reference frame attached to
      a spinous process, the ultrasonography probe, and surgical instruments. Five- and
      10-MHz phased-array ultrasonography probes equipped with optical tracking frames
      were used for image data acquisition. Spinal cord tumors were visualized using
      ultrasonography, and 3D ultrasonography-guided tumor biopsy sampling and
      resection were performed. The practice of attaching the reference frame to a
      spinous process adjacent to the spinal cord tumor, as well as performing image
      acquisition just before starting the resection, reduced the possible sources of
      inaccuracy. The technical application of a navigation system based on
      intraoperative 3D ultrasound image reconstruction seems feasible and may have the
      potential of improving functional outcome in association with spinal cord tumor
      surgery.

PMID- 16961091
TI  - Expandable cage placement via a posterolateral approach in lumbar spine
      reconstructions. Technical note.
AB  - The authors describe a technique for inserting an expandable cage via a posterior
      extracavitary approach while protecting the segmental nerves. The advent of
      expandable cages has allowed the use of a less invasive anterior access to the
      spine, thereby decreasing the surgery-induced insult to the patient. In an
      attempt to minimize this trauma, the authors have used a posterolateral approach
      that has allowed them to perform neural decompression, anterior reconstruction
      with an expandable cage, and posterior stabilization with posterior pedicle
      screws. The authors describe their surgical technique of posterior
      circumferential decompression, which entails the use of an expandable cage that
      is inserted at 90 degrees, rotated in place where the corpectomy has been
      performed, and then expanded with special custom-made tools, thus respecting the
      segmental nerves of the lumbar spine. One case example is provided to illustrate
      the technique.

PMID- 16961092
TI  - Two-component signal transduction systems as key players in stress responses of
      lactic acid bacteria.
AB  - Lactic acid bacteria (LAB) continue as an important group of gram-positive
      bacteria that have been extensively exploited in food industries and various
      biotechnological applications. Some LAB species are, however, opportunistic
      pathogens and were reported to be associated with overwhelming number of human
      infections. During the use of LAB in industry or over the course of human
      infection, these bacteria are exposed to environmental stress. While LAB display
      adaptive mechanisms to cope with adverse conditions, the regulation of these
      mechanisms remains to be elucidated. Recent completion of genome sequencing of
      various LAB strains combined with the development of advanced molecular
      techniques have enabled the identification of a number of putative two-component
      signal transduction systems, also known as two-component regulatory systems
      (2CRS), in LAB. Examining the effect of deleting genes specifying putative 2CRS
      proteins in these organisms has revealed the involvement of 2CRS in the responses
      of LAB to different stresses. There are lines of evidence indicating that certain
      2CRS may mediate a general stress response in Enterococcus faecalis and
      Streptococcus pyogenes. This review highlights the influence of 2CRS on the
      physiology of LAB during optimal growth and survival/growth on exposure to
      environmental stress.

PMID- 16961093
TI  - Materials in the design of kettles.
AB  - This article reviews the materials used in the production of kettles since the
      Victorian times, why they have changed over time, and what material may be used
      in the future for kettle production, but first, to investigate what materials
      have been used in the production of kettles, the use of the item needs to be
      understood. The definition of a kettle is: "A covered metal or plastic container
      with handle and shaped opening for pouring used for boiling water."

PMID- 16961094
TI  - The chemistry of the bio-control agent, Trichoderma harzianum.
AB  - The role of 6-n-pentyl-2H-pyran-2-one and other metabolites of the fungus
      Trichoderma harzianum, in its application as a bio-control agent, is discussed.

PMID- 16961095
TI  - Quality assuring managed care.

PMID- 16961096
TI  - Viewing Kaiser Permanente via the logistician lens.
AB  - PURPOSE: The aim of this paper is to undertake a holistic comparison between NHS
      and Kaiser Permanente (KP) healthcare delivery systems.
      DESIGN/METHODOLOGY/APPROACH: The paper reviews in detail the many papers and
      communications published on KP via the "logistics lens" which is focussed on
      smooth patient flow from onset of problem to completion of treatment. FINDINGS:
      The paper finds that healthcare "best practice" is readily related to
      conventional supply chain performance metrics and engineering change model
      attributes. Much of the apparent success of KP is due to cultural and
      organisational factors. A noteworthy example deserving wide dissemination and
      application is in the effectiveness of interfaces between clinicians and
      managers. RESEARCH LIMITATIONS/IMPLICATIONS: This review exposes the need for the
      NHS to be driven by end-to-end processing times rather than the present salami
      principle of separating in-patient, out-patient and other queues into neat
      statistics, which can be meaningless to an individual patient. PRACTICAL
      IMPLICATIONS: Introduces clinicians and healthcare professionals to a range of
      tools and techniques for engineering "best practice". This method is well
      understood and proven in other areas of application. Particular aspects of the KP
      study are thus confirmatory of what is actually happening in small pockets of the
      NHS. ORIGINALITY/VALUE: The paper provides a new perspective on the performance
      of healthcare supply chains. New knowledge and deeper understanding of the
      mechanisms of success emerge from a study adopting a different viewpoint.

PMID- 16961097
TI  - Pathways, networks and choice in health care.
AB  - PURPOSE: The purpose of the paper is to present an alternative to the supply
      chain model of health care delivery that currently informs most thinking about
      the design of care processes. DESIGN/METHODOLOGY/APPROACH: The paper draws on
      arguments from systems theories and public administration, to generate an
      analysis of the nature of health care processes. It sets out a model of services
      characterised by treatment and care needs that vary over time, that are
      inherently uncertain, involve frequent assessment and re-assessment, and provide
      patients and service providers with choices about treatment and care. Evidence
      from an evaluation of intermediate care is used to illustrate the analysis.
      FINDINGS: The analysis suggests that both the supply chain and a more network
      like model of health care processes can help us to understand health care
      processes. The two are complementary. RESEARCH LIMITATIONS/IMPLICATIONS: Largely
      conceptual in nature. The empirical evidence is taken from one study. The ideas
      are presented to stimulate thinking rather than to prove an argument. PRACTICAL
      IMPLICATIONS: The conceptualisation of care processes as network-like has
      implications for the way in which we think about the design and performance of
      health care systems. ORIGINALITY/VALUE: There have been few publications that
      seek to use both systems and network approaches to understand health care
      processes.

PMID- 16961098
TI  - Touch-screen versus paper-and-pen questionnaires: effects on patients'
      evaluations of quality of care.
AB  - PURPOSE: The aim of the paper is to compare the computer administration method
      (touch-screen) with the original paper-and-pen approach when measuring patients'
      perceptions of care quality. DESIGN/METHODOLOGY/APPROACH: The study group
      consisted of 199 patients who responded to touch-screen and 219 who responded to
      paper-and-pen questionnaires, receiving care between January and March 2003 at
      two out-patient clinics in one county in Sweden. The response rate was 75 per
      cent. A modified version of the quality from the patient's perspective
      questionnaire was used. FINDINGS: Two main findings emerged: first, both methods
      yielded almost identical results in quality of care ratings, and second, the
      touch-screen method was perceived to be easier to use and to take less time to
      complete. ORIGINALITY/VALUE: The paper shows that both methods are acceptable,
      but the touch-screen method appears to be preferred by patients.

PMID- 16961099
TI  - Using the balanced scorecard to measure Chinese and Japanese hospital
      performance.
AB  - PURPOSE: The objective of the paper is to confirm the feasibility and value of
      using the balanced scorecard (BSC) to measure performance in two hospitals in
      different countries. DESIGN/METHODOLOGY/APPROACH: One hospital from China and
      another from Japan were chosen and key indicators were selected according to the
      BSC framework. A comparative hospital performance measurement model was set up
      using the BSC framework to comprehensively compare hospital performance in two
      countries. FINDINGS: The BSC was found to be effective for underlining existing
      problems and identifying opportunities for improvements. The BSC also revealed
      the hospitals' contribution to performance improvement of each country's total
      health system. RESEARCH LIMITATIONS/IMPLICATIONS: Hospital performance
      comparisons between countries using the BSC depend on the selection of feasible
      and appropriate key performance indicators, which is occasionally limited by data
      collection problems. ORIGINALITY/VALUE: The first use of the BSC to compare
      hospital performance between China and Japan shows benefits that not only
      suggests performance improvements in individual hospitals but also reveals
      effective health factors allowing implementation of valid national health
      policies.

PMID- 16961101
TI  - Patient-centredness.

PMID- 16961100
TI  - HACCP and the management of healthcare associated infections: are there lessons
      to be learnt from other industries?
AB  - PURPOSE: Hospital cleaning and healthcare associated infections (HCAIs) continue
      to attract adverse media attention and consumer concern. Parallels exist with
      similar publicity relating to cleaning and food safety in the food industry
      almost 13 years earlier. This paper examines some of the management solutions
      developed in the food industry, and discusses their application to healthcare
      delivery. DESIGN/METHODOLOGY/APPROACH: The food industry is managing food safety
      by adopting a dual approach based on pre-requisite programmes and Hazard Analysis
      Critical Control Points (HACCP). How these differ is described and how the
      approaches and terminology can be adapted for use in healthcare is discussed.
      FINDINGS: The food industry is moving towards external certification of safety
      using national and international standards. The HACCP approach, a management tool
      and a central requirement of these standards, is evolving and there is interest
      worldwide from the healthcare community. Its application to the decontamination
      of endoscopes, using conventional HACCP, is presented, as well as suggestions for
      a simplified format for managing patient-related procedures. Taking this type of
      approach to the management of HCAIs could provide greater transparency, reduce
      infection rates and increase consumer confidence. PRACTICAL IMPLICATIONS:
      Potential problems in adopting HACCP, including cost and human resource, are
      discussed. ORIGINALITY/VALUE: The HACCP method/approach has previously been
      mentioned in the medical literature but this paper is one of the few to examine,
      from basic principles, its infection control application within a broader
      approach to quality assurance.

PMID- 16961102
TI  - "Personal excellence" as a value for health professionals: a patient's
      perspective.
AB  - PURPOSE: To bring to the attention of health care professionals a framework and
      set of ideas for conceptualising a typical patient's experience and ways to
      respond out of a subjective inner quality called personal excellence.
      DESIGN/METHODOLOGY/APPROACH: This paper essays the viewpoint of the author on a
      selection of his experiences as a patient over 19 hospital admissions during his
      lifetime. He integrates these findings with his understanding of personal
      construct psychology, the psychology of change and the Greek philosophical
      concept of "arete" or excellence. FINDINGS: The paper offers a theory that
      patients experience three kinds of emotions or anguish when admitted to hospitals
      called threat, fear and anxiety. These three ways of interpreting an experience
      of change are based on the diagnostic constructs of transition from the
      psychology of personal constructs or the psychology of change. The paper asserts
      that a holistic approach is more likely to be delivered by health care staff with
      a calling than those who are merely doing a job or pursuing a career.
      ORIGINALITY/VALUE: This paper is significant in that it draws on authentic
      experiences of a patient that are conceptualised into a coherent framework and
      linked to a well-accepted theory within the science of psychology. Further it
      offers an alternative to essays on quality that are confined to objective
      features only. It offers a way, via the philosophical concept of "arete" to tap
      into the subjective attitudinal dimension of quality that is often the lever or
      more often the impediment to enabling quality improvement programmes to be
      effective.

PMID- 16961103
TI  - The use of collaboration in personal outcomes.
AB  - PURPOSE: As part of its restructuring and commitment to collaboration and
      advances in healthcare, the author's organisation has recently adopted personal
      outcomes to ensure that services are aligned to meet patient needs more
      effectively. The purpose of this paper is to evaluate this advancement in
      healthcare in the light of recent research findings, changing policies and the
      author's own understanding. DESIGN/METHDODOLOGY/APPROACH: The paper introduces
      the concept of collaboration as a means of achieving personal outcomes. In
      addition, the paper puts forward suggestions as to how the nurse can foster
      interdisciplinary/multidisciplinary teamwork, utilising the core concepts of the
      advanced nurse practitioner, namely transformational leadership, in support of
      this. FINDINGS: While success stories of personal outcomes abound much of it
      anecdotal based. Therefore, the need to initiate research in this area is of
      paramount importance as the latter would be helpful in examining meaningful
      quality outcomes. Reform in structure, finance and policy will also be necessary,
      as these are vital ingredients to the success of personal outcomes. Despite the
      overlapping conflict of Irish government policy, the extra finance announced in
      the 2005 Budget can only serve to assist organisations in achieving accreditation
      through initiatives like personal outcomes. Central to the success of personal
      outcomes, is to engage in collaborative practice by way of fostering
      interdisciplinary/multidisciplinary team working. RESEARCH
      LIMITATIONS/IMPLICATIONS: Further study of the impact on patient outcomes of
      collaboration is warranted. ORIGINALITY/VALUE: The paper examines organisational,
      professional and interpersonal challenges.

PMID- 16961104
TI  - Measuring quality in services for children with an intellectual disability.
AB  - PURPOSE: To evaluate the application of one particular quality measurement tool,
      the SERVQUAL instrument, as a potential mechanism to measure quality in services
      for children with disabilities DESIGN/METHODOLOGY/APPROACH: Staff and family of
      children with an intellectual disability in two organisations providing
      specialist therapy and day completed an adapted SERVQUAL questionnaire. A total
      of 81 SERVQUAL questionnaires were distributed and 59 questionnaires were
      returned (response rate of 73 per cent). FINDINGS: The SERVQUAL instrument can be
      considered as a useful diagnostic tool to identify particular strengths and areas
      for improvement in services for people with disabilities as the instrument lends
      itself for the monitoring of the effectiveness of quality improvement initiatives
      over time. The findings also showed relatively high customer expectations and the
      organisations involved in this research are currently not meeting all of these
      high expectations as significant quality gaps were found in the areas of
      reliability and responsiveness. RESEARCH LIMITATIONS/IMPLICATIONS: The sample
      size was relatively small and the measurement of quality using the SERVQUAL
      instrument remains a challenge, due to the conceptual and empirical difficulties.
      PRACTICAL IMPLICATIONS: The SERVQUAL instrument is probably most be attractive to
      service managers and funding organisations because of its ability to identify
      gaps in the quality of the service. ORIGINALITY/VALUE: The tool had been used to
      measure quality in services for people with disabilities and the research has
      shown that this tool might be an important additional quality measurement tool
      for services.

PMID- 16961105
TI  - Moral distress in the pediatric intensive care unit: the impact on pediatric
      nurses.
AB  - PURPOSE: The purpose of this paper is to explore the concept of moral distress in
      particular as it impacts on the pediatric intensive care nurse caught between
      caring for infants and children who would not otherwise be alive were it not for
      the advances of modern medical technology, and their personal beliefs concerning
      the societal value of life at any cost. DESIGN/METHODOLOGY/APPROACH: Describes
      cases and real incidents to illustrate the moral distress experienced by-these
      nurses caught between caring for the children and at the same time interacting
      with the families. Such families are too often living on hope, with a profound
      faith in the ever advancing world of medical technology to keep loved ones alive
      with little thought to the consequences. FINDINGS: Suggests that the impact of
      moral distress on pediatric nurses, particularly as it relates to burnout, may
      well jeoparidize their ability to deliver effective care and is another
      unrecognized cost in the medical world. PRACTICAL IMPLICATIONS: Suggests that an
      ethical approach to care is necessary through hard to answer questions. Due to
      the fact that such questions are not often addressed, the author suggests
      consideration be given to medical ethicists to mediate and assist those caught in
      this dilemma. ORIGINALITY/VALUE: This paper will be of value to those concerned
      with how medical and life-saving technologies are outstripping our human
      abilities to comprehend and live with the consequences, and some of the ethical
      issues that arise.

PMID- 16961106
TI  - Consumer beware: a few words about accreditation.
AB  - PURPOSE: The purpose of this paper is to point out the dangers inherent in
      choosing schools or programs from the internet, particularly in the field of
      health services, which may not be accredited, and therefore not recognized either
      by other institutions or by employers. DESIGN/METHODOLOGY/APPROACH: The problem
      is described and some of the better known American accrediting agencies are
      listed. PRACTICAL IMPLICATIONS: The paper has practical implications in terms of
      providing useful steps for anyone interested in exploring a health services
      career through ongoing education. ORIGINALITY/VALUE: The paper represents a
      viewpoint from the perspective of an American accreditation consultant who is
      familiar with the organizational and program accreditation system in the USA.

PMID- 16961107
TI  - The value of a mission statement in an association of not-for-profit hospitals.
AB  - PURPOSE: When a mission statement is introduced to enhance the quality of health
      care management, it is vital to assess the actual impact. This article aims to
      consider the effect of introducing a single mission statement into an association
      of 18 not-for-profit hospitals by investigating the views of different groups of
      employees. DESIGN/METHODOLOGY/APPROACH: The paper explores the impact a mission
      statement has had by examining questionnaire responses from different groups of
      staff including the designers of the mission statement and those at the delivery
      point of services. FINDINGS: The study's outcomes indicate the value of examining
      the views of staff that are not in senior management. The evaluation of the
      mission statement's impact by senior managers was at variance with that of other
      staff. ORIGINALITY/VALUE: The findings highlight the inadequacy of only examining
      senior management's opinions when considering the benefits of having introduced a
      mission statement into an organisation. In this study we identify those who
      originated or contributed to the mission statement in the first place. Once
      launched, a mission statement can have an impact throughout all staff, and that
      information needs to be captured in any assessment. This is consistent with the
      high rating normally given to a mission statement being an aid to motivating all
      staff. An important dimension of this study is the impact of a single mission
      statement throughout a group of dissimilar hospitals.

PMID- 16961108
TI  - Life enrichment programme; enhanced dining experience, a pilot project.
AB  - PURPOSE: The purpose of this pilot project is to highlight how food intake,
      nutrition status and quality of life could be improved for long stay residents of
      a community nursing unit and demonstrate that assisted feeding can be a more
      dignified experience for them. DESIGN/METHODOLOGY/APPROACH: A good dining
      experience involves not just the food, but also its presentation and the
      environment in which it is served. A review of the literature identified projects
      with similar objectives but differing approaches. A survey of residents informed
      the planning phase. A home style dining room was created with a more traditional
      ambiance and decoration. The pace of dining was leisurely. Personal choice and
      independence in eating were supported. A schedule of dining activities was
      delivered by two staff facilitators. FINDINGS: Eight dining sessions facilitated
      23 residents over three months. "Minced" meals were not served, help was given to
      cut up meat and cues or prompts offered to maximize independence and demonstrate
      the value of this approach to care staff. ORIGINALITY/VALUE: The project
      illustrated the advantages of stepping outside the purely clinical framework in
      addressing issues around poor food intake. It highlighted and how small but
      valuable changes can be implemented even where resources and space is limited.
      Involvement with the project allowed staff to observe and reflect on the benefits
      of enhancing the social and aesthetic aspects of dining.

PMID- 16961109
TI  - Quality assessment of family planning services in urban health centers of Shahid
      Beheshti Medical Science University, 2004.
AB  - PURPOSE: Quality of family planning services is now considered as a global
      concern and importance. The purpose of the present study is to assess quality of
      family planning services in the urbanhealth centers of Shahid Beheshti Medical
      Science University. DESIGN/METHODOLOGY/APPROACH: This was a descriptive study to
      assess structure, process and outcome of the family planning care services. A
      total of 15 health centers of Shahid Beheshti Medical Science University were
      randomized and the quality of provided care by 65 family planning care providers
      of these health centers were observed and assessed using checklists. A total of
      75 family planning clients were interviewed to assess their knowledge about their
      selected family planning method all of whom completed the related forms of
      satisfaction with the services. The tools for data collection were two
      observational checklists, and two questionnaires with subsequent data analyzed
      using SPSS 11.5. In total 75 clients with an average age 24 (7 +/- 4) (mean +/-
      SD) participated in the study. The provision of family planning services by 65
      providers was assessed by observation at three intervals. Of the providers, 60
      (92.3 per cent) were midwives. FINDINGS: Mean satisfaction score of clients was
      83.3 +/- 9.05 percent meaning clients were highly satisfied with the services.
      Mean knowledge score of clients about their family planning method of use was
      59.1 +/- 18 percent, which shows their moderate knowledge about their method of
      use. ORIGINALITY/VALUE: A more advanced tool to assess quality of care of family
      planning services with more focus on special care for the contraceptives was
      developed. Quality of care in family planning services of Shahid Beheshti Medical
      Science University health centers showed adequate facilities and equipment and to
      have trained personnel however their client's knowledge about the selected method
      was moderate. Therefore, interventional programs are needed to improve counseling
      and the educational process of clients, which should be considered in future
      research and planning of the programs.

PMID- 16961110
TI  - The meaning of evidence-based nursing.

PMID- 16961111
TI  - Nurses' fears and professional obligations concerning possible human-to-human
      avian flu.
AB  - This survey aimed to illustrate factors that contribute to nurses' fear when
      faced with a possible human-to-human avian flu pandemic and their willingness to
      care for patients with avian flu in Taiwan. The participants were nursing
      students with a lesser nursing credential who were currently enrolled in a
      bachelor degree program in a private university in southern Taiwan. Nearly 42% of
      the nurses did not think that, if there were an outbreak of avian flu, their
      working hospitals would have sufficient infection control measures and equipment
      to prevent nosocomial infection in their working environment. About 57% of the
      nurse participants indicated that they were willing to care for patients infected
      with avian influenza. Nurses' fear about an unknown infectious disease, such as
      the H5N1 influenza virus, could easily be heightened to levels above those
      occurring during the 2003 severe acute respiratory syndrome outbreak in Taiwan.

PMID- 16961112
TI  - Opportunities and obstacles for good work in nursing.
AB  - Good work in nursing is work that is scientifically effective as well as morally
      and socially responsible. The purpose of this study was to examine variables that
      sustain good work among entering nurses (with one to five years of experience)
      and experienced professional nurses despite the obstacles they encounter. In
      addition to role models and mentors, entering and experienced nurses identified
      team work, cohesiveness and shared values as levers for good work. These nurses
      used prioritization, team building and contemplative practices to overcome
      obstacles. Entering professional nurses tended to avoid conflict in the work
      setting. Experienced nurses reported forming teams of decision makers who share
      similar values to resolve conflict. These findings have implications for nurse
      education and nursing practice. Reflection on the importance of values and virtue
      in sustaining good work is important. Entering professional nurses should be
      encouraged to seek positive role models and reflect on the lessons that can be
      learned from experienced exemplary nurses.

PMID- 16961113
TI  - An Iranian perspective on patients' rights.
AB  - The aim of this phenomenological research study carried out in Iran was to
      capture the meaning of patients' rights from the lived experiences of patients
      and their companions. To achieve this, 12 semistructured interviews were
      conducted during 2005 in a teaching hospital in Tehran with patients and/or their
      companions. In addition, extensive field notes were compiled during the
      interviews. The data were analyzed using Benner's thematic analysis. The themes
      captured were classified into three main categories, with certain themes
      identified within each category. The categories were: (1) the concept of
      patients' rights; (2) barriers to patients' rights; and (3) facilitators of
      patients' rights. The distinctive themes within each of the categories were
      identified as: (1a) receiving real care, (1b) focus on the patient, and (1c)
      equality and accessibility; (2a) dissatisfaction with caregivers, and (2b)
      specific work environment limitations; (3a) the patient's companion, (3b) a
      responsible system, and (3c) the public's awareness of rights. Although certain
      themes identified closely resemble those identified in international patients'
      bills of rights, the current study focused on themes that are particularly
      relevant to the Iranian sociocultural context.

PMID- 16961114
TI  - Conditions for patient participation and non-participation in health care.
AB  - This study explored patients' experiences of participation and non-participation
      in their health care. A questionnaire-based survey method was used. Content
      analysis showed that conditions for patient participation occurred when
      information was provided not by using standard procedures but based on individual
      needs and accompanied by explanations, when the patient was regarded as an
      individual, when the patient's knowledge was recognized by staff, and when the
      patient made decisions based on knowledge and needs, or performed self-care.
      Thus, to provide conditions for true patient participation, professionals need to
      recognize each patient's unique knowledge and respect the individual's
      description of his or her situation rather than just inviting the person to
      participate in decision making.

PMID- 16961115
TI  - Understanding privacy in occupational health services.
AB  - The aim of this study was to gain a deeper understanding of privacy in
      occupational health services. Data were collected through in-depth theme
      interviews with occupational health professionals (n = 15), employees (n = 15)
      and employers (n = 14). Our findings indicate that privacy, in this context, is a
      complex and multilayered concept, and that companies as well as individual
      employees have their own core secrets. Co-operation between the three groups
      proved challenging: occupational health professionals have to consider carefully
      in which situations and how much they are entitled to release private information
      on individual employees for the benefit of the whole company. Privacy is thus not
      an absolute right of an individual, but involves the idea of sharing
      responsibility. The findings open up useful new perspectives on ethical questions
      of privacy and on the development of occupational health practices.

PMID- 16961116
TI  - Belgian nurses' views on codes of ethics: development, dissemination,
      implementation.
AB  - The aim of this study was to explore how Belgian nurses view issues related to
      the development, dissemination and implementation of a code of ethics for nurses.
      Fifty nurses took part in eight focus groups. The participants stated that, on
      the whole, a code of ethics for nurses would be useful. They stressed that a code
      should be a practical and useful instrument developed by nurses for nurses, and
      that it should be formulated and presented in a practical way, just as
      educational courses dealing specifically with codes of ethics require a practical
      approach to be effective. They emphasized that the development of a code should
      be an ongoing process, enabling nurses to provide input as they reflect on the
      ethical issues dealt with in the code and apply the code in their practice.
      Finally, they stressed the need for support at institutional level for the
      effective implementation of a code.

PMID- 16961117
TI  - Moral deliberation in psychiatric nursing practice.
AB  - Moral deliberation has been receiving more attention in nursing ethics. Several
      ethical conversation models have been developed. This article explores the
      feasibility of the so-called CARE (Considerations, Actions, Reasons, Experiences)
      model as a framework for moral deliberation in psychiatric nursing practice. This
      model was used in combination with narrative and dialogical approaches to foster
      discourse between various stakeholders about coercion in a closed admission
      clinic in a mental hospital in the Netherlands. The findings demonstrate that the
      CARE model provides a substantial framework for structuring moral deliberations.
      Narratives and dialogue are useful tools for broadening issues in conversations,
      to engage various stakeholders (including patients), and to gain shared
      understandings.

PMID- 16961118
TI  - An assessment of medical ethics education.

PMID- 16961119
TI  - Co-operation or catastrophe.

PMID- 16961120
TI  - Global health and national security: the need for critical engagement.
AB  - The security and foreign policy communities have increasingly addressed global
      health problems as threats to national security. Global health is a humanitarian
      endeavour that seeks to improve the world's health including the most vulnerable
      peoples, while national security works to protect the interests of people within
      a given state. The major statements of security policy by the United States and
      United Kingdom link the self-protective interests of national security with the
      humanitarian objectives of global health. While there is potential to expand
      global health activities through partnership with the security and foreign policy
      communities, treating global health issues as national security threats may focus
      attention disproportionately on countries or diseases which pose security threats
      to wealthy nations, rather than on the greatest threats to global health. The
      global health community should carefully scrutinise areas where global health and
      national security interests overlap.

PMID- 16961121
TI  - Impact of proliferation of small arms and light weapons in south Asia.
AB  - Small arms and light weapons (SALW) cause much death and injury around the world,
      through war, homicide and suicide. The problems of SALW in south Asia have to be
      seen within a global context, but the region itself has special concerns which
      must be understood by the world. Ultimately these issues will only be resolved
      through international co-operation, which in turn requires people to become
      active in urging their political leaders to take the right path.

PMID- 16961122
TI  - Health implications of small arms and light weapons in eastern Uganda.
AB  - Injuries due to small arms and light weapons (SALW) are common in developing
      countries with ongoing collective violence, or those that exist in a post
      conflict state. Uganda has a long history of armed conflict, but little
      quantitative evidence is available about the extent of the problem of SALW. We
      performed a review of all injuries due to SALW at Mbale Regional Hospital in
      eastern Uganda for the six-year period 1998-2003. Using a standardised
      questionnaire, we recorded information from over 200 cases concerning the
      characteristics of the victim, the incident, the weapon used and the care
      received. The majority involved males and occurred in the context of conflict
      within tribal communities, or armed robberies throughout the region. Each injury
      is of significant cost to the healthcare system and to the victim. Prevention,
      through limiting the availability of the 'vector' of disease (SALW), is a key
      part of the solution to this problem.

PMID- 16961123
TI  - The end of biomilitary realism? Rethinking biomedicine and international
      security.
AB  - Medicine and politics have a common aim, the welfare of people, and the ideas and
      language of one influence the other. There are parallels between medicine,
      particularly its more cutting-edge aspects, and international affairs; and the
      more aggressive forms of medicine, like the more aggressive forms of
      international relationships, seem to be about short-term gain, based on little
      evidence, with longer-term negative consequences as the full impact of the action
      becomes clear. Modem medicine has been very effective in curative methods, but
      the fundamentals of public health, which receive less kudos, have perhaps had
      more beneficial effects. The world of international affairs can learn much from a
      holistic and public health approach.

PMID- 16961124
TI  - Intergroup atrocities in war: a neuroscientific perspective.
AB  - Studying the most extreme outcomes of intergroup hatred--murder, mass killings
      and genocides--has long been part of historical and social research.
      Neuroscientists and psychologists have also been interested in interpersonal and
      intergroup violence. This article considers the question of how atrocities arise
      from a neuroscientific perspective, focusing on war as the context in which they
      most often occur. It describes relevant aspects of brain function, relates them
      to social psychological research on intergroup hostility and applies the
      resulting framework to a case study: the US prison camp at Guantanamo Bay.

PMID- 16961125
TI  - An end to nuclear madness: IPPNW European Meeting, Aubagne.

PMID- 16961126
TI  - Osteogenesis imperfecta.

PMID- 16961127
TI  - Skull base abnormalities in osteogenesis imperfecta: a cephalometric evaluation
      of 54 patients and 108 control volunteers.
AB  - OBJECT: Osteogenesis imperfecta (OI), which usually results from mutations in
      type I collagen genes, causes bone fragility and deformities. The head is often
      abnormally shaped, and changes in skull base anatomy in the form of basilar
      impression and basilar invagination have been reported. The authors analyzed the
      skull base anatomy on standardized lateral cephalograms from 54 patients with OI
      (Types I, III, and IV) and 108 control volunteers. They were surprised to find
      that the previously used diagnostic measures for basilar abnormality in patients
      with OI were exceeded in 6.5 to 7.4% of the controls, and hence needed to be
      reevaluated. METHODS: The authors calculated the distance from the odontoid
      process to four reference lines, including a novel one, in the controls. The
      normal mean distances were exceeded by more than two standard deviations (SDs) in
      28.3 to 35.2%, and by more than three SDs in 13.2 to 16.6% of the patients with
      OI. The latter figures reliably reflect the prevalence of basilar impression. As
      a sign of basilar invagination the odontoid process protruded into the foramen
      magnum or reached the foramen magnum level in 22.2% of the patients with OI,
      whereas none of the controls showed this feature. Platybasia (an anterior cranial
      base angle > 146 degrees) was present in 11.1% of the patients but in none of the
      controls. CONCLUSIONS: Platybasia, basilar impression, and basilar invagination
      were often coexpressed, but each was also present as an isolated abnormality.
      These three abnormalities and wormian bones were predominantly found in OI Types
      III and IV as well as in patients exhibiting dentinal abnormality.

PMID- 16961128
TI  - Brain metastasis.

PMID- 16961129
TI  - Results of a phase II trial of the GliaSite radiation therapy system for the
      treatment of newly diagnosed, resected single brain metastases.
AB  - OBJECT: The aim of this study was to evaluate the effectiveness of brachytherapy
      using the GliaSite Radiation Therapy System in patients with a newly diagnosed
      resected single brain metastasis. The primary end point of the study was local
      tumor control. The secondary end points included patient survival, distant brain
      recurrence, quality of life, and treatment toxicity. METHODS: The authors
      conducted a prospective multiinstitutional phase II study of GliaSite
      brachytherapy prescribed at a 60-Gy dose administered to a 1-cm depth after
      resection of a single brain metastasis. No whole-brain radiation therapy was
      given. Patients were assessed at 1 and 3 months after brachytherapy and every 3
      months thereafter for up to 2 years. Seventy-one patients were enrolled at 13
      centers. A GliaSite balloon catheter was implanted in 62 patients. Fifty-four
      patients received brachytherapy. The median patient age was 60 years. The most
      common tumor (54%) was non-small cell lung cancer. Fifty-seven percent of
      patients had brain metastasis only, whereas 43% had extracranial metastasis. The
      median final administered dose was 60 Gy. The magnetic resonance imaging-
      determined local control rate, based on several different methods, was 82 to 87%.
      Both the median patient survival time and the median duration of functional
      independence were 40 weeks. Among the 35 patients who died, the cause of death
      was neurological in 11%. Thirteen patients underwent reoperation for suspected
      tumor recurrence or radiation necrosis, and histological diagnoses included
      radiation necrosis without tumor (nine patients), radiation necrosis mixed with
      tumor (two patients), and tumor only (two patients). Extracranial metastasis,
      tumor size, and radiation necrosis were significant factors affecting patient
      survival. CONCLUSIONS: In patients with a resected single brain metastasis,
      GliaSite brachytherapy leads to a local control rate, median patient survival
      time, and duration of functional independence similar to those achieved with
      resection plus whole-brain radiation therapy.

PMID- 16961130
TI  - Phase II study of nimustine, carboplatin, vincristine, and interferon-beta with
      radiotherapy for glioblastoma multiforme: experience of the Kyoto Neuro-Oncology
      Group.
AB  - OBJECT: This Phase II study was performed to determine the safety, tolerability,
      and efficacy of combining nimustine (ACNU)-carboplatin-vincristine-Interferon
      beta (IFNbeta) chemotherapy. METHODS: Ninety-seven patients with Karnofsky
      Performance Scale scores of 50 or greater were enrolled in the study. Nimustine
      (60 mg/m2), carboplatin (110 mg/m2), vincristine (0.6 mg/m2), and IFNbeta (10
      microg) were administered on Day 1 concomitant with radiotherapy (63 Gy);
      vincristine (0.6 mg/m2) and IFNbeta (10 microg) on Days 8 and 15; and IFNbeta
      alone (10 microg) three times per week throughout the course of radiotherapy.
      Fifty-six days after radiotherapy ended, the time schedule for chemotherapy was
      reset and ACNU, carboplatin, vincristine, and IFNbeta were again administered on
      the new Day 1 and vincristine and IFNbeta on the new Days 8 and 15. This course
      was repeated every 56 days. Instances of nonhematological toxicity were rare and
      mild. During the course of radiotherapy, the percentages of patients who
      experienced Grade 3 toxicity were 14% with neurocytopenia and 7% with
      thrombocytopenia. Seven percent of all adjuvant chemotherapy cycles following
      radiotherapy were associated with Grade 3 toxicity, as manifested in
      neurocytopenia or thrombocytopenia. No instance of Grade 4 toxicity was observed.
      The median duration of progression-free survival was 10 months (95% confidence
      interval [CI] 8-12 months) and the median duration of overall survival was 16
      months (95% CI 13-20 months). CONCLUSIONS: The combination of ACNU-carboplatin
      vincristine-IFNbeta chemotherapy and radiotherapy is safe and well tolerated, and
      may prolong survival in patients with glioblastoma multiforme.

PMID- 16961131
TI  - Balloon-assisted coil embolization of intracranial aneurysms.

PMID- 16961132
TI  - Complications of balloon-assisted coil embolization of intracranial aneurysms.

PMID- 16961133
TI  - Balloon-assisted coil embolization of intracranial aneurysms: incidence,
      complications, and angiography results.
AB  - OBJECT: The aim of this study was to assess the incidence, indications,
      complications, and angiography results associated with balloon-assisted coil
      embolization (BACE) of intracranial aneurysms and to compare these factors with
      those for conventional coil embolization (CE). METHODS: Between 1995 and 2005,
      827 intracranial aneurysms in 757 consecutive patients were packed with coils.
      Balloon-assisted coil embolization was used in 8.6% (71 of 827) of the coil
      insertion procedures and was more frequently used in large aneurysms, unruptured
      lesions, and those located on the vertebrobasilar system and carotid artery.
      Procedure-related complications leading to death or dependency were significantly
      higher in BACEs (14.1%) compared with those in CEs (3%). Packing densities and
      the results of 6-month follow-up angiography studies did not differ significantly
      between the two types of treatments. There was a strong trend for a higher
      retreatment rate in the aneurysms treated with BACE. CONCLUSIONS: Balloon
      assisted coil embolization of intracranial aneurysms is associated with a high
      complication rate and should only be used if conventional CE of these lesions is
      impossible or has failed and if anticipated surgical risks are too high. The BACE
      procedure does not improve the occlusion rates of the aneurysms on follow-up
      evaluation.

PMID- 16961134
TI  - Blood blister-like aneurysms at nonbranching sites of the internal carotid
      artery.
AB  - OBJECT: The clinical features of blood blister-like aneurysms (BBAs) that arise
      at nonbranching sites of the internal carotid artery (ICA) differ from those of
      saccular aneurysms. In this study, the authors attempt to describe optimal
      treatments for BBAs, which have yet to be clearly established. METHODS: Ten of
      483 patients with aneurysmal subarachnoid hemorrhage who had been seen at the
      authors' institution between March 2001 and June 2005 had intraoperatively
      confirmed BBAs at nonbranching sites of the ICA. All ten patients were women
      between the ages of 37 and 64 years (mean age 49.3 years); five had a history of
      hypertension. The BBAs were localized to the right side of the ICA in seven
      cases. All patients were successfully treated; clipping was undertaken in six,
      clipping combined with wrapping in three, and trapping in one. These methods were
      used in conjunction with various other surgical techniques such as brain
      relaxation by draining cerebrospinal fluid, anterior clinoidectomy, exposing the
      cervical ICA, gentle subpial dissection (for aneurysms that adhered to the
      frontal lobe), complete trapping of the ICA before clipping, and protecting the
      brain. Clip slippage occurred at the end of dural closing in two cases; the
      aneurysm was completely obliterated using multiple clips combined with ICA
      stenosis in one of these cases and ICA trapping with good collateral flow in the
      other. An excellent clinical outcome was achieved in eight patients, whereas two
      patients were disabled from massive vasospasm. The authors retrospectively
      reviewed radiological and surgical data in all cases to determine which treatment
      methods produced a favorable outcome. CONCLUSIONS: Blood blister-like aneurysms
      located at nonbranching sites of the ICA are difficult to treat. Preoperative
      awareness and careful consideration of these lesions during surgery can prevent
      poor clinical outcomes.

PMID- 16961135
TI  - Three-dimensional rotational angiography guidance for aneurysm surgery.
AB  - OBJECT: The aim of this study was to investigate the feasibility of integrating
      three-dimensional rotational angiography (3D-RA) data into a surgical navigation
      system and to assess its accuracy and potential clinical benefit. METHODS: The
      study cohort consisted of 16 patients with 16 intracranial aneurysms who had been
      scheduled for routine or emergency surgery. Rotational angiography data were
      exported using a virtual reality modeling language file format and imported into
      the BrainLAB VectorVision2 image-guided surgery equipment. During 3D-RA the
      position of the head was measured using a special headframe. The authors also
      determined the accuracy of 3D-RA image guidance and the clinical benefit as
      judged by the surgeon, including, for example, early identification of branching
      vessels and the aneurysm. There was good correspondence between the 3D-RA-based
      navigation data and the intraoperative vascular anatomy in all cases, with a
      maximum error of 9 degrees of angulation and 9 degrees of rotation. In eight
      cases, the surgeon determined that the 3D-RA image guidance facilitated the
      surgical procedure by predicting the location of the aneurysm or the origin of a
      branching artery that had been covered by brain tissue and blood clots.
      CONCLUSIONS: The integration of 3D-RA into surgical navigation systems is
      feasible, but it currently requires a new perspective-registration technique. The
      intraoperative 3D view provides useful information about the vascular anatomy and
      may improve the quality of aneurysm surgery in selected cases.

PMID- 16961136
TI  - Influence of intraventricular hemorrhage and occlusive hydrocephalus on the long
      term outcome of treated patients with basal ganglia hemorrhage: a case-control
      study.
AB  - OBJECT: Only limited data exist addressing the long-term outcome of patients with
      ganglionic hemorrhage complicated by intraventricular hemorrhage (IVH) and
      hydrocephalus that requires an external ventricular drain (EVD). The aim of this
      study was to compare the long-term outcome of patients with pure ganglionic
      hemorrhage and those requiring an EVD due to additional IVH and hydrocephalus.
      METHODS: For this study, 116 patients with supratentorial ganglionic hemorrhage
      and occlusive hydrocephalus were screened. To avoid any bias the authors excluded
      all patients with nonprimary intracerebral hemorrhage as well as those who
      received no treatment. Forty patients with IVH and subsequent hydrocephalus were
      examined, and 40 more patients with pure ganglionic hematomas were matched with
      regard to age, sex, Glasgow Coma Scale score, need for mechanical ventilation,
      and, in particular, hematoma volume. Outcome analysis was performed using the
      Barthel Index and the modified Rankin Scale (mRS). The mean hematoma volume was
      25.3 +/- 15.2 ml. The overall long-term outcome was unfavorable (mRS Score 4-6)
      in 59% of all patients. Good outcome (mRS score < 4) was observed in 25 (62.5%)
      of 40 patients with hematoma volumes less than 25 ml, compared with eight (20%)
      of 40 who had hematoma volumes greater than 25 ml (p < 0.05, chi-square test).
      The need for an EVD was not associated with a worse long-term outcome in patients
      with comparable hematoma volumes. In contrast, the duration of treatment in the
      intensive care unit was longer for patients with EVDs than for those who had pure
      ganglionic hematomas (16 [range 5-29] days compared with 8 [range 2-19] days; p <
      0.05, Mann-Whitney U-test), regardless of hematoma volume. CONCLUSIONS: The long
      term outcome of treated patients with supratentorial ganglionic hemorrhage with
      ventricular involvement and occlusive hydrocephalus is comparable to that of
      patients with similar hematoma volumes but no IVH.

PMID- 16961137
TI  - The role of MMP-2 and MMP-9 polymorphisms in sporadic intracranial aneurysms.
AB  - OBJECT: Matrix metalloproteinases (MMPs) are a family of endopeptidases that
      mediate vascular remodeling by degrading extracellular matrix components, such as
      collagen and elastin. On the basis of accumulating evidence that implicates
      increased MMP-2 (gelatinase A) and MMP-9 (gelatinase B) amounts and activity in
      the pathogenesis of aneurysms, the authors investigated the genetic association
      between polymorphisms in MMP-2 and MMP-9 and sporadic intracranial aneurysms.
      METHODS: Eight polymorphisms located in MMP-2 and MMP-9 were genotyped, and the
      association of these variations with disease was assessed in a Caucasian
      population consisting of 125 patients with intracranial aneurysms and 234
      ethnically matched healthy volunteers. Polymorphisms in the MMP-2 gene and the
      haplotypes generated from these polymorphisms were not associated with the
      occurrence of intracranial aneurysms. However, a polymorphism located in the 3'
      untranslated region of MMP-9 showed a significant association with disease in the
      study population, with individuals carrying the TT genotype at increased risk for
      developing intracranial aneurysms (odds ratio 1.91, p = 0.005). Haplotypes
      containing the T allele of this polymorphism also showed a comparable association
      with disease. Similar results were obtained in an analysis of these polymorphisms
      in a subgroup of patients who presented with ruptured aneurysms. CONCLUSIONS: The
      study findings support a role for MMP-9, but not MMP-2, in the pathogenesis of
      intracranial aneurysms.

PMID- 16961138
TI  - Lysis of intracerebral hematoma with stereotactically implanted tissue
      plasminogen activator polymers in a rabbit model.
AB  - OBJECT: Currently no adequate surgical treatment exists for spontaneous
      intracerebral hemorrhage (ICH). Implantable polymers can be used effectively to
      deliver therapeutic agents to the local site of the pathological process, thus
      reducing adverse systemic effects. The authors report the use of stereotactically
      implanted polymers loaded with tissue plasminogen activator (tPA) to induce lysis
      of ICH in a rabbit model. METHODS: Ethylene vinyl acetate (EVAc) polymers were
      loaded with bovine serum albumin (BSA) only or with BSA plus tPA. In vitro
      pharmacokinetic (three polymers) and thrombolysis (12 polymers) studies were
      performed. For the in vivo study, 12 rabbits were fixed in a stereotactic frame,
      and 0.2 ml of clotted autologous blood was injected into the right frontal lobe
      parenchyma. After 20 minutes, control BSA polymers were stereotactically
      implanted at the hemorrhage site in six rabbits, and experimental BSA plus tPA
      polymers were implanted in six rabbits. Animals were killed at 3 days, and blood
      clot volume was assessed. The pharmacokinetic study showed release of 146 ng of
      tPA over 3 days. The tPA activity correlated with in vitro thrombolysis. In the
      in vivo study, the six animals treated with tPA polymers had a mean (+/- standard
      error of the mean [SEM]) thrombus volume of 1.43 +/- 0.29 mm3 at 3 days, whereas
      the six animals treated with blank (BSA-only) polymers had a mean (+/- SEM)
      thrombus volume of 19.99 +/- 3.74 mm3 (p < 0.001). CONCLUSIONS: Ethylene vinyl
      acetate polymers release tPA over the course of 3 days. Stereotactic implantation
      of tPA-loaded EVAc polymers significantly reduced ICH volume. Polymers loaded
      with tPA may be useful clinically for lysis of ICH without the side effects of
      systemic administration of tPA.

PMID- 16961139
TI  - Prolongation of survival following depletion of CD4+CD25+ regulatory T cells in
      mice with experimental brain tumors.
AB  - OBJECT: Regulatory CD4+CD25+ T cells have been shown to play an important role in
      the regulation of the immune response. Whereas the presence of these cells has
      been associated with immune suppression, the lack of regulatory T (Treg) cells
      has been shown to induce autoimmunity. The purpose of this study was to define
      the role of Treg cells in tumors of the central nervous system (CNS). METHODS:
      The authors implanted syngeneic GL261 tumor cells in the brains or flanks of
      C57BL/6 mice. The resulting tumors were later removed at specific time points,
      and the presence of tumor-infiltrating lymphocytes was analyzed by performing
      flow cytometry for the presence of Treg cells. In a separate experiment, mice
      with GL261 tumors were treated with injections of anti-CD25 monoclonal antibody
      (mAb) to determine whether depletion of Treg cells may have an impact on the
      length of survival in mice with brain tumors. Tumor-infiltrating lymphocytes
      isolated from mice with GL261 tumors were found to have a significant increase in
      the presence of Treg cells compared with control lymphocytes (p < 0.05).
      Moreover, Treg cells isolated in murine brain tumors expressed FoxP3, CTLA-4, and
      CD62L. Mice treated with anti-CD25 mAb lived significantly longer than tumor
      bearing control animals (p < 0.05). An analysis of brains in surviving animals
      showed a depletion of CD4+CD25+ T cells. CONCLUSIONS: The results of this study
      indicate that CD4+CD25+ Treg cells play an important role in suppressing the
      immune response to CNS tumors. These Treg cells may therefore represent a
      potentially novel target for immunotherapy of malignant gliomas.

PMID- 16961140
TI  - Gene expression and molecular changes in cerebral arteries following subarachnoid
      hemorrhage in the rat.
AB  - OBJECT: The authors investigated early changes in the cerebral arteries of rats
      that occur after subarachnoid hemorrhage (SAH). METHODS: Messenger RNA was
      investigated by performing microarray and quantitative real-time polymerase chain
      reaction (PCR) analyses, and protein expression was shown by performing
      immunohistochemical studies. The array data indicated that the initial processes
      that occur after SAH involve activation of genes involved in angiogenesis,
      inflammation, and extracellular matrix (ECM) remodeling. The real-time PCR
      investigation confirmed upregulation of genes that were observed using the
      microarray to be regulated, including iNOS, MMP13, and cxcl2. The authors also
      verified the upregulation of previously implicated genes for G-protein-coupled
      receptors (endothelin B [ETB], angiotensin 1 [AT1], and AT2) and
      metalloproteinase 9. The results of an immunohistochemical study confirmed that
      receptor genes that were seen to be regulated produced an increase in protein
      expression. Double immunostaining of rat cerebral arteries with endothelial cell-
      or smooth-muscle cell-specific antibodies verified that an increase in ETB, 5
      hydrotryptamine (5-HT1B), and 5-HT1D receptor expression occurs in smooth-muscle
      cells. CONCLUSIONS: Processes occurring after SAH lead to enhanced arterial
      contractility and ECM remodeling either directly or through angiogenesis and
      inflammation. These processes are active via an increase in metalloproteinase
      expression, the presence of proangiogenic factors, and the expression of
      proinflammatory genes.

PMID- 16961141
TI  - Focal disruption of the blood-brain barrier due to 260-kHz ultrasound bursts: a
      method for molecular imaging and targeted drug delivery.
AB  - OBJECT: The goal of this study was to explore the feasibility of using low
      frequency magnetic resonance (MR) image-guided focused ultrasound as a
      noninvasive method for the temporary disruption of the blood-brain barrier (BBB)
      at targeted locations. METHODS: Rabbits were placed inside a clinical 1.5-tesla
      MR imaging unit, and sites in their brains were targeted for 20-second burst
      sonications (frequency 260 kHz). The peak pressure amplitude during the burst
      varied between 0.1 and 0.9 MPa. Each sonication was performed after an
      intravenous injection of an ultrasound contrast agent (Optison). The disruption
      of the BBB was evaluated with the aid of an injection of an MR imaging contrast
      agent (MAG-NEVIST). Additional tests involving the use of MION-47, a 20-nm
      magnetic nanoparticle contrast agent, were also performed. The animals were
      killed at different time points between 3 minutes and 5 weeks postsonication,
      after which light or electron microscopic evaluation was performed. The threshold
      for BBB disruption was approximately 0.2 MPa. More than 80% of the brain sites
      sonicated showed BBB disruption when the pressure amplitude was 0.3 MPa; at 0.4
      MPa, this percentage was greater than 90%. Tissue necrosis, ischemia, and
      apoptosis were not found in tissue in which the pressure amplitude was less than
      0.4 MPa; however, in a few areas of brain tissue erythrocytes were identified
      outside blood vessels following exposures of 0.4 MPa or higher. Survival
      experiments did not show any long-term adverse events. CONCLUSIONS: These results
      demonstrate that low-frequency ultrasound bursts can induce local, reversible
      disruption of the BBB without undesired long-term effects. This technique offers
      a potential noninvasive method for targeted drug delivery in the brain aided by a
      relatively simple low-frequency device.

PMID- 16961142
TI  - Recurrent late cerebral necrosis with aggressive characteristics after
      radiosurgical treatment of an arteriovenous malformation. Case report.
AB  - /Late cerebral radiation necrosis usually occurs within 3 years of stereotactic
      radiosurgery. The authors report on a case of recurrent radiation necrosis with
      rapid clinical deterioration and imaging findings resembling those of a malignant
      glioma. This 68-year-old man, who had a history of a left posterior temporal and
      thalamic arteriovenous malformation (AVM) treated with linear accelerator
      radiosurgery 13 years before presentation and complicated by radiation necrosis
      11 years before presentation, exhibited new-onset mixed aphasia, right
      hemiparesis, and right hemineglect. Imaging studies demonstrated hemorrhage and
      an enlarging, heterogeneously enhancing mass in the region of the previously
      treated AVM. The patient was treated medically with corticosteroid agents, and
      stabilized temporarily. Unfortunately, his condition worsened precipitously soon
      thereafter, requiring the placement of a shunt for relief of obstructive
      hydrocephalus. Further surgical intervention was offered, but the patient's
      family opted for hospice care instead. The patient died 10 weeks after initially
      presenting to the authors' institution, and the results of an autopsy
      demonstrated radiation necrosis. Symptomatic radiation necrosis can occur more
      than a decade after stereotactic radiosurgery, necessitating patient follow up
      during a longer period of time than currently practiced. Furthermore, there is a
      need for more careful reporting on the natural history of such cases to clarify
      the pathogenesis of very late and recurrent radiation necrosis after radiosurgery
      and to define patient groups with a higher risk for these entities.

PMID- 16961143
TI  - Oligodendroglioma of the pineal region. Case report.
AB  - The authors describe an oligodendroglioma of the pineal region in a 59-year-old
      woman. The patient presented with intermittent confusion, memory disturbance, and
      headache associated with a cystic pineal region mass demonstrated on magnetic
      resonance imaging. Gross-total resection was performed via a suboccipital
      supratentorial approach. Pathological and genetic evaluation showed the tumor to
      be an anaplastic oligodendroglioma. Although the spectrum of tumors arising
      within the region of the pineal gland is broad, to the authors' knowledge this is
      the first report of an oligodendroglioma occurring in this area.

PMID- 16961144
TI  - Tako-tsubo cardiomyopathy: reversible heart failure with favorable outcome in
      patients with intracerebral hemorrhage. Case report.
AB  - In patients with intracerebal hemorrhage, cardiac dysfunction is a common
      phenomenon. Tako-tsubo cardiomyopathy is characterized by complete reversibility
      and therefore may constitute an entity with a favorable outcome. In this case
      report the authors describe a previously healthy 23-year-old man with no history
      of cardiac disease who suffered a severe fourth ventricular hemorrhage due to an
      angioma of the vermis cerebelli. After emergency surgery, progressive
      tachycardia, fibrillation, and electromechanical decoupling developed in the
      patient. An echocardiogram revealed left ventricular apical akinesia and basal
      hyperkinesis characteristic of tako-tsubo cardiomyopathy. One week after
      admission, cardiac function was normal. Tako-tsubo cardiomyopathy differs from
      common cardiac dysfunction in its reversible nature. This characteristic must be
      taken into consideration when treating patients with intracerebral hemorrhage to
      avoid misclassification of the disease.

PMID- 16961145
TI  - Angiographically occult, progressively expanding, giant vertebral artery
      aneurysm. Case report.
AB  - Hunterian ligation is a well-known treatment for complex aneurysms not amenable
      to direct microsurgical clip application. After proximal parent vessel occlusion,
      cerebral angiography is typically used to confirm aneurysm thrombosis. The
      authors report on a vertebral artery (VA) aneurysm that had progressively
      expanded and caused brainstem compression after hunterian ligation, despite
      nondiagnostic findings on both conventional and computed tomography (CT)
      angiography at multiple time points. This 64-year-old woman underwent hunterian
      ligation of a 1.8-cm VA aneurysm at the origin of the right posterior inferior
      cerebellar artery. An immediately postoperative conventional angiogram and follow
      up CT angiograms obtained 5 and 6 years postligation confirmed complete
      obliteration of the lesion. Nine years after the initial surgery, however, the
      patient experienced neurological deterioration. Although CTs showed substantial
      aneurysm enlargement together with pontine compression, angiograms once again
      demonstrated complete right VA occlusion with no retrograde filling of the
      aneurysm. On reexploration, the aneurysm was effectively debulked, clipped, and
      obliterated. Arterial bleeding was found in the lesion neck, as was evidence of
      microrecanalization. Hunterian ligation for complex aneurysms carries the risk of
      microrecanalization and lesion expansion despite nondiagnostic angiography.
      Although this ligation procedure remains a viable treatment option in carefully
      selected patients, an extended follow-up evaluation period may be required even
      when imaging suggests aneurysm obliteration.

PMID- 16961146
TI  - Central brain herniation secondary to fulminant acute disseminated
      encephalomyelitis: implications for neurosurgical management. Case report.
AB  - Acute disseminated encephalomyelitis (ADEM), also known as postinfectious
      encephalomyelitis, is an immunologically mediated demyelinating disorder
      affecting the central nervous system that typically occurs after infection or
      vaccination. The prognosis of ADEM is generally favorable. In a small subset of
      patients with ADEM, however, fulminant cerebral edema requiring neurosurgical
      intervention will develop. Few recommendations are available to help the
      neurosurgeon in dealing with such cases. In this report, the authors present the
      case of a patient with ADEM in whom central brain herniation developed secondary
      to medically intractable cerebral edema. The authors review the salient features
      of the disease and suggest a role for neurosurgeons in cases of fulminant ADEM.

PMID- 16961147
TI  - Very low pressure hydrocephalus. Report of two cases.
AB  - Low-pressure hydrocephalus is an extremely rare condition. Authors of the few
      previous reports on this subject have suggested that symptoms are gradual in
      onset and successfully treated. In this report the authors presented two unique
      cases of very low pressure hydrocephalus in which the patients experienced rapid
      deterioration requiring negative-pressure cerebrospinal fluid drainage to achieve
      the best possible neurological function; outcomes in both patients ultimately
      were poor. The constellation of findings suggests that this may be a distinct
      clinical entity.

PMID- 16961148
TI  - Retrograde suction decompression of giant paraclinoid aneurysms using a No. 7
      French balloon-containing guide catheter. Technical note.
AB  - The treatment of large and giant paraclinoid carotid artery (CA) aneurysms often
      requires the use of suction decompression for safe and effective occlusion. Both
      open and endovascular suction decompression techniques have been described
      previously. In this article the authors describe a revised endovascular suction
      decompression technique that provides several advantages in the treatment of
      large and giant paraclinoid and CA aneurysms. A 51-year-old woman presented with
      a relatively brief history of progressive visual loss in the right eye,
      nonspecific headache, and an afferent pupillary defect. After angiography studies
      had been obtained, it was determined that she had a giant right paraclinoid
      internal CA aneurysm with a dome size of approximately 26 mm on the right and a
      neck diameter of 10 mm. A modified technique was performed in which suction
      decompression was used. With the aid of a No. 7 French Concentric balloon guide
      catheter (Concentric Medical, Inc., Mountain View, CA) and application of a
      temporary clip distal to the aneurysm, the aneurysm was trapped and decompressed
      using retrograde suction through the guide catheter when the balloon was
      inflated. After satisfactory placement of three permanent clips, an
      intraoperative angiogram obtained through the same guide catheter confirmed CA
      patency. The aneurysm was then punctured and aspirated, ensuring complete
      occlusion of the aneurysm sac and reconstruction of the parent vessel. The
      patient made an excellent recovery and did not suffer any complications. She did
      not experience worsening in her vision. This technical modification to
      endovascular suction decompression allows several potential advantages, including
      higher volume decompression and the ability to deliver endovascular devices to
      distal arterial locations.

PMID- 16961149
TI  - Establishing tumor cell lines from aggressive telomerase-positive chordomas of
      the skull base. Technical note.
AB  - Permanent cell cultures are invaluable tools for understanding the biological
      characteristics of tumors. In the present study the authors report on the
      establishment of permanent human cell lines from three cases of aggressive
      chordomas of the clival region. All of the parental tumors showed telomerase
      activity. Cultured chordoma cells had a doubling time of 5 to 7 days and grew as
      a monolayer of cells that retained both the immunophenotype and the p53 status of
      the parental tumor. In vitro, chordoma cells overexpressed telomerase, supporting
      the hypothesis that this enzyme is required for the immortalization process.

PMID- 16961150
TI  - Intraoperative ventricular puncture during supraorbital craniotomy via an eyebrow
      incision. Technical note.
AB  - The authors determined the landmarks and coordinates for intraoperative
      ventricular puncture directly from the supraorbital craniotomy opening via an
      eyebrow incision. Fifty magnetic resonance (MR) imaging studies were obtained
      from patients with no pathological cerebral characteristics or ventricular
      distortion. The cerebral entry point of the ventriculostomy was located directly
      under the key bur hole (just behind the zygomatic process of the frontal bone) at
      the base of the frontal lobe because it represents a stable, reliable point that
      can be used as the bur hole during supraorbital craniotomy via an eyebrow
      incision. From this point, the coordinates for lateral ventricular puncture were
      determined using MR imaging studies and neuronavigational software. The cerebral
      entry point of the ventriculostomy was situated directly under the key bur hole
      at the base of the frontal lobe. The catheter was directed at a 45 degrees angle
      to the midline and a 20 degrees angle up from an imaginary line parallel to the
      orbitomeatal line. The catheter will usually be inserted into the ventricle at a
      point 5 cm deep to the cortex and may be inserted as deep as 6.5 cm. Using this
      technique, the frontal horn of the lateral ventricle can be easily tapped. The
      landmark required for this technique is readily available in all patients.

PMID- 16961151
TI  - Personal recollections of Walter E. Dandy and his brain team.
AB  - Walter Edward Dandy (1886-1946) began his surgical training at the Johns Hopkins
      Hospital in 1910 and joined the faculty in 1918. During the next 28 years at
      Johns Hopkins, Dandy established a neurosurgery residency training program that
      was initially part of the revolutionary surgical training system established by
      William S. Halsted but eventually became a separate entity. Dandy's residents
      were part of his "Brain Team," a highly efficient organization that allowed Dandy
      to perform over 1000 operations per year, not counting ventriculograms. This team
      also provided rigorous training in the Halsted mold for the neurosurgical
      residents. Although exacting and demanding, Dandy was universally admired by his
      residents and staff. This article describes Dandy's neurosurgical residency
      program at Johns Hopkins, and provides personal recollections of training under
      Walter Dandy.

PMID- 16961152
TI  - Bo Sung Sim (1924-2001): a pioneer of neurosurgery in Korea.
AB  - Bo Sung Sim (1924-2001) stands as a prominent figure in the history of Korean
      neurosurgery. His devoted contributions have led to the fruitful development of
      modern neurosurgery in Korea. Sim practiced advanced neurosurgical techniques,
      undertook basic research, was passionate about education in the early years of
      neurosurgery in Korea, and played an essential role in founding the Korean
      Neurosurgical Society. Sim was a true neurosurgeon-a teacher, a scientist, and a
      superb pioneer in Korean neurosurgery.

PMID- 16961153
TI  - Ependymoma.

PMID- 16961154
TI  - Brain O2.

PMID- 16961155
TI  - Brain O2.

PMID- 16961156
TI  - Ventriculostomy infections.

PMID- 16961157
TI  - Clinical impact of CYP2C19 polymorphism on the action of proton pump inhibitors:
      a review of a special problem.
AB  - Proton pump inhibitors (e.g. omeprazole/esomeprazole, lansoprazole, pantoprazole,
      rabeprazole) have a prominent role in the short- and long-term management of acid
      related intestinal disease. They are eliminated by the hepatic route and the
      polymorphic CYP2C19 is involved in their metabolism. Three phenotypes have been
      identified in various populations: extensive metabolizers (homEM), poor
      metabolizers (PM) and individuals carrying one wild type and one mutant allele
      (hetEM). Therefore, systemic drug exposure (AUC) varies widely between these
      three populations and the AUC for omeprazole, lansoprazole and rabeprazole are
      approximately 7.5-, 4.5- and 4-fold higher in PM than in homEM. Since the
      pharmacodynamic response to proton pump inhibitors (PPIs) is related to their
      AUC, intragastric pH is much more elevated in PM (median around 6) and hetEM (4 -
      5) than in homEM (3 - 4). This genotype-dependent increase in AUC and
      intragastric pH has clinical consequences because the healing rate in peptic
      ulcer (PU, target pH > or = 3) and gastroesophageal reflux disease (GERD, target
      pH > or = 4) and the eradication of Helicobacter pylori (Hp) depend on a long
      lasting (> or = 16 hours) and effective inhibition of acid secretion. Several
      clinical studies have shown that PM and hetEM benefit from an approximately 18%
      higher Hp eradication rate compared to homEM when standard dosages of PPIs are
      administered orally. In our own study with lansoprazole (+ amoxicillin,
      clarithromycin, metronidazole) the eradication rates were 100, 98 and 80% in PM,
      hetEM and homEM, respectively, and in patients with GERD treated with
      lansoprazole (30 mg/day) the healing rates after 8 weeks were much higher in PM
      (85 - 100%) and hetEM (68 - 95%) than in homEM (46 - 77%). In a further study
      with esomeprazole (40 mg/day) in 205 patients with GERD we were surprised to
      observe that the healing rate after 4 weeks was not dependent on the CYP2C19
      genotype. In an accompanying pharmacokinetic trial in 10 patients with GERD, both
      esomeprazole and 5-OH-esomeprazole (formed by CYP2C19) plasma levels and those of
      omeprazole-sulfone (formed by CYP3A4) were determined. Based on the calculated
      metabolic ratios it could be shown that CYP3A4 plays a major role in kinetics of
      esomeprozale, particularly after multiple dosing when there is a metabolic shift
      in favor of the formation of the sulfone. In conclusion, for most PPIs the
      activity of CYP2C 19 determines the level of drug exposure (AUC), pharmacodynamic
      response (elevation of intragastric pH and serum levels of gastrin) and clinical
      outcome (Hp eradication, healing rates of PU and GERD). Thus, a genotype-adjusted
      dosage regimen will improve therapeutic efficacy of PPIs.

PMID- 16961158
TI  - Maturational changes in the in vivo activity of CYP3A4 in the first months of
      life.
AB  - OBJECTIVE: To document maturational changes of the in vivo activity of CYP3A4 in
      the first months of life. METHODS: The contribution of tramadol (M), O-demethyl
      tramadol (M1, CYP2D6-mediated) and N-demethyl tramadol (M2, CYP3A4-mediated) to
      the overall elimination of tramadol and the log M/M2 was assessed in 24-hour
      urine collections during continuous intravenous tramadol administration.
      Correlations with perinatal characteristics (postnatal age (PNA) and
      postmenstrual age (PMA)) were studied. RESULTS: Of the total amount of tramadol
      administered in a 24-hour interval to 25 neonates and young infants (PMA 25 - 53
      weeks), 34.5% (SD 6.1) were retrieved in the urine as parent compound or
      metabolite in a 24-hour interval. This retrieved material consisted primarily of
      tramadol 79% (SD 18), M1 10% (SD 17) and M2 3% (SD 3.4). The contribution of M
      (r2 = -0.53), M1 (r2 = 0.46) and M2 (r2 = 0.16) to overall M elimination
      correlated with increasing PMA. The mean log M/M2 was 1.44 (SD 0.46) and there
      was an inverse correlation between the log M/M2 ratio and PMA (r2 = -0.43, 95% CI
      for r = -0.84 to -0.34, p = 0.0006) and PNA (r2 = -0.25, 95% CI for r = -0.78 to 
      0.16, p = 0.008). The maturational half-life of the log M/M2 ratio was 16 - 20
      weeks. In a multiple regression model, PMA was the only significant variable
      accounting for the interindividual variability in log M/M2. CONCLUSIONS: PMA was
      found to be the most important maturational change determing the in vivo activity
      of CYP3A4. The activity of CYP3A4 is relatively delayed in the first months of
      life compared to the developmental changes in CYP2D6 activity described earlier,
      however, the overall weak correlations reflect that PMA explains only in part the
      interindividual variability observed.

PMID- 16961159
TI  - Glucocorticoid treatment in patients with septic shock: effects on vasopressor
      use and mortality.
AB  - Corticosteroids were proposed for the treatment of sepsis as early as 1940.
      Several RCTs cast serious doubts on the usefulness of high dose corticosteroids
      and doubt still persists regarding the efficacy of replacement therapy. Adrenal
      insufficiency (non-responders to the 250 microg corticotropin test: increase in
      cortisol < 9 microg/dl) is present in about half of patients with septic shock
      and is associated with higher rates of refractory hypotension and mortality.
      Peripheral glucocorticoid resistance, which may even occur more frequently, can
      be easily assessed at bedside using skin tests. Cortisol antagonizes the
      migration of inflammatory cells, the synthesis or action of virtually all
      proinflammatory mediators, promotes virtually all anti-inflammatory components
      and enhances humoral immunity by means of transcriptional interference between
      its receptor and both AP-1 and NF-kappaB. Cortisol mediates cardiovascular
      tolerance to endotoxin and the maintenance of vascular sensitivity to
      catecholamines. Low doses (about 300 mg daily for 5 days or more) of
      hydrocortisone increase vasoconstrictor response to catecholamines in animals, in
      healthy volunteers challenged with LPS and in several RCTs. Hydrocortisone also
      increases arterial pressure and decreases the duration of shock. A meta-analysis
      of all available clinical controlled studies showed a reduction in 28 days, all
      cause mortality with glucocorticoids (RR = 0.88, 95% CI: 0.78 - 1.00; p = 0.04).
      However, there was a significant heterogeneity across the trials (p = 0.006). On
      the other hand, analysis of studies where low doses of glucocorticoids were given
      for prolonged periods showed a 24% reduction in the risk of all-cause mortality
      at 28 days in treated patients (RR = 0.76, 95% CI: 0.64 - 0.90; p = 0.002)
      without heterogeneity across the trials (p = 0.28). In conclusion, in severe
      sepsis, high doses of corticosteroids should not be given. Septic shock should be
      treated with a replacement dose of hydrocortisone.

PMID- 16961160
TI  - Dipyridamole/aspirin combination in secondary stroke prevention: effects on
      absolute myocardial blood flow and coronary vascular resistance.
AB  - OBJECTIVE: In the European Stroke Prevention Study (ESPS 2), oral administration
      of a fixed combination of 200 mg extended-release dipyridamole and 25 mg aspirin
      (twice daily) after ischemic stroke or transient ischemic attack, significantly
      reduced the risk of stroke compared to placebo as well as compared to aspirin or
      dipyridamole alone. However, the i.v. application of dipyridamole over 4 - 6 min
      is known to increase myocardial blood flow up to 6-fold, and thereby potentially
      provoke ischemic wall motion abnormalities in patients with coronary artery
      disease. We therefore assessed the cardiac side effects of the
      dipyridamole/aspirin combination on absolute myocardial blood flow (MBF) and
      coronary vascular resistance (CVR). METHODS: MBF and CVR were measured using 150
      water positron emission tomography in 24 patients after stroke or transient
      ischemic attack, before and 6.7 +/- 1.9 days after starting the
      dipyridamole/aspirin combination (Aggrenox) therapy. RESULTS: Resting MBF
      increased by 39% (max. 112%), from 0.92 +/- 0.13 (ml x g(-1) x min(-1)) at
      baseline to 1.28 +/- 0.27 (ml x g(-1) x min(-1)) under ongoing
      dipyridamole/aspirin combination therapy (p < 0.0005). CVR consecutively
      decreased from 105.3 +/- 16.9 to 74.1 +/- 16.5 (mmHg x ml(-1) x g x min) (p <
      0.0005). The relative increase in MBF correlated negatively with the body surface
      area. No correlation was found between relative MBF increase and duration of
      dipyridamole/aspirin combination therapy (range 4 - 10 days). CONCLUSIONS: Orally
      administered dipyridamole/aspirin combination therapy in secondary stroke
      prevention increases MBF and decreases CVR significantly. These cardiac side
      effects of the dipyridamole/aspirin combination should be taken into account in
      stroke patients with proven or suspected coronary artery disease, particularly in
      combination with a small body surface area.

PMID- 16961161
TI  - Pharmacokinetic interaction between ketoconazole and SPP301 in healthy
      volunteers.
AB  - BACKGROUND: SPP301 is a potent and highly selective ETA receptor blocker. The
      primary aim of the present study was to investigate the effect of the potent
      CYP3A4 inhibitor ketoconazole on the pharmacokinetics of SPP301. METHODS: In a
      randomized, open-label 2-period oral crossover study, 12 healthy male subjects
      received treatments A and B. Treatment A consisted of 200 mg ketoconazole once
      daily on Days 1 - 4 and concomitantly 5 mg SPP301 on Day 3. Treatment B consisted
      of 5 mg SPP301 administered alone. Plasma concentrations of SPP301 and its
      hydroxymethyl metabolite were measured by LC-MS/MS. RESULTS: Ketoconazole
      coadministration increased the systemic availability of SPP301 and its
      hydroxymethyl metabolite 3-fold and prolonged their half-lives by a factor of 2.
      The ratios of least square means (90% CI) of pharmacokinetic parameters in the
      presence and absence of ketoconazole for SPP301 and its metabolite were C(max)
      (maximum plasma concentration) 1.22 (1.13, 1.32) and 1.2 (1.05, 1.37), AUC(0
      infinity) (area under the plasma concentration-time curve from time zero to
      infinity) 3.16 (2.84, 3.51) and 3.14 (2.49, 3.70) and t1/2 (apparent terminal
      half-life) 2.21 (1.55, 2.87) and 2.00 (1.17, 2.84), i.e. an increase of systemic
      exposure by a factor of 3.2, with individual exposures increasing up to 5.9-fold.
      Single oral doses of SPP301 were well tolerated when administered alone or
      together with multiple doses of ketoconazole. CONCLUSION: In the presence of
      potent CYP3A4 inhibitors exposure of SPP301 may be increased up to 6-fold.

PMID- 16961162
TI  - Possible macular exanthema associated with linezolid therapy.
AB  - OBJECTIVE: To report a case of macular exanthema associated with linezolid
      therapy. CASE SUMMARY: A 54-year-old white man diagnosed as having laryngeal
      epidermoid carcinoma attended our emergency department because of fatigue, fever,
      neck pain and a fistulized fixed mass in the right side of the neck with purulent
      exudation. Treatment with amoxicillin/clavulanic acid 875 mg/125 mg p.o. every 8
      hours as empirical therapy was started. Cultures of the exudates from the fistula
      confirmed the presence of methicillin-resistant Staphylococcus aureus (MRSA).
      Amoxicillin/clavulanic acid was discontinued and therapy was started with
      linezolid 600 mg p.o. every 12 hours but 5 days after commencing linezolid the
      patient came to our emergency room because of generalized erythematous macular
      eruptions. A diagnosis of severe and generalized macular exanthema induced by
      linezolid was made. Administration of linezolid was suspended and there was an
      improvement in the skin lesions and general state of health. The patient was
      discharged without further symptoms. DISCUSSION: In this case, there was a close
      temporal correlation between drug exposure and the onset of symptoms. When
      linezolid was discontinued, the skin lesions resolved quickly and the general
      condition of the patient improved. Furthermore, linezolid was the only drug added
      before the cutaneous lesions appeared. It is possible that the adverse reaction
      was associated with administration of amoxicillin/clavulanic acid. However, the
      patient had been treated with this antibiotic previously without appearance of
      any cutaneous reaction. An objective causality assessment revealed that an
      adverse effect was possible. CONCLUSION: Based on our observations, we conclude
      that linezolid was the most likely cause of the adverse reaction. Clinicians
      should be aware of this infrequent but severe reaction.

PMID- 16961163
TI  - Potentially inappropriate prescribing for insomnia in elderly outpatients in
      Taiwan.
AB  - OBJECTIVE: This study was based on Taiwan's National Health Insurance (NHI) claim
      records with the aim of identifying specific types of potentially inappropriate
      sedative-hypnotic prescribing in elderly outpatients with insomnia. The
      potentially inappropriate prescribing included duplicate treatment, excessive
      dosage and duration or treatment and prescribing of hypnotics that are too long
      acting. MATERIAL AND METHODS: This cross-sectional study was based on annual
      outpatient claim data for 2001 released by Taiwan's Bureau of National Health
      Insurance (BNHI). A subset was created for patients aged 65 years or older and
      coded as having insomnia. Physician consultation claim data were extracted and
      merged in 1 claim file consisting of ICD-9-CM codes, patient demographic data,
      specialty of physicians, medical institution code and pharmaceutical prescription
      content. RESULTS: Elderly patients with insomnia constituted 216,994 of the
      1,000,193 files surveyed on outpatient claims in 2001. The mean age was 74.33
      years and gender distribution was nearly equal. Of the prescribed sleep
      medications, 41.26% were hypnotic benzodiazepines, 29.36% were hypnotic non
      benzodiazepines and 29.38% were sedative-anxiolytics. Approximately 1 in 25
      patients (4.12%) of all the patients prescribed hypnotics received duplicate
      treatment, 1 in 8 an inappropriately (12.27%) high dosage (daily dose > 1.5 DDD,
      Defined Daily Dose), 1 in 3 (32.25%) more than 28 DDD per prescription and 1 in 6
      (17.52%) a drug with an effect which was too prolonged. Physicians tended to
      consider patient gender but not age when prescribing. Clear trends were found
      between the specialty of the physician and the type of inappropriate prescribing.
      The type of medical institution was significantly related only to the excessive
      quantity of medication prescribed. CONCLUSIONS: Elderly people in Taiwan with
      insomnia receive potentially inappropriate prescriptions for sleep medications.
      Similar data could possibly be extracted from similar databases in other
      countries throughout the world. Some of these potentially inappropriate
      prescriptions are avoidable in terms of restricting the length of outpatient
      sedative-hypnotic treatment, introducing hypnotics in small dosage forms and
      continuously educating clinicians on the safety of geriatric medication.

PMID- 16961164
TI  - Nephro-pharmacology.

PMID- 16961165
TI  - Nebivolol: a review of its clinical and pharmacological characteristics.
AB  - Nebivolol is a cardioselective lipophilic beta-blocker devoid of intrinsic
      sympathomimetic and membrane-stabilizing actions. The pharmacological profile
      differs from that of conventional cardioselective beta3-blockers in that it
      displays nitric oxide- (NO) mediated vasodilator activity. The net hemodynamic
      effect of nebivolol is the result of a balance between the depressant effects of
      beta3-blockade and an action that tends to maintain cardiac output, presumably
      connected with its afterload reducing vasodilator effect. Recent studies suggest
      that nebivolol may also restore endothelial dysfunction. Long-term follow-up
      studies indicate that the compound is efficacious and safe both in patients with
      mild hypertension and those with stable angina. An interesting effect of chronic
      nebivolol therapy in elderly patients with mild hypertension is the reversal of a
      depressor effect into a pressor effect on standing. This action indicates that
      nebivolol has advantages over other antihypertensive drugs and that it may
      protect elderly hypertensive patients from orthostatic complaints. The
      observation that nebivolol improves exercise capacity in non-claudicant
      hypertensives is also of clinical interest. Nebivolol resembles serotonin
      reuptake inhibitors in that it is metabolized by CYP450 2D6 and, therefore,
      concomitant treatment with serotonin uptake inhibitors may lead to overdosing.
      Nebivolol compared to placebo does not significantly reduce the mortality risk in
      elderly subjects. The effects of biological age and comorbidities may be
      responsible for this finding. In conclusion, clinical studies suggest that
      nebivolol is effective and safe in patients with hypertension, angina pectoris
      and heart failure. The beneficial effects on endothelial function, autonomic
      control and exercise capacity are of considerable clinical interest.

PMID- 16961166
TI  - Gabapentin versus nortriptyline in post-herpetic neuralgia patients: a
      randomized, double-blind clinical trial--the GONIP Trial.
AB  - BACKGROUND: Gabapentin and nortriptyline have not been compared in a randomized
      trial in post-herpetic neuralgia (PHN). The present study was, therefore,
      undertaken to determine their comparative efficacy and tolerability in the
      treatment of post-herpetic neuralgia. PATIENTS AND METHODS: The study was a
      randomized, double-blind, parallel-group trial of 9 weeks duration. Adult PHN
      patients with history of > 8 weeks of PHN pain after healing of rash, a pain
      intensity of at least 40 mm on a 100 mm visual analog scale at screening and at
      randomization, and average pain score of at least 4 on the Likert scale during
      the baseline week were included in the study. Gabapentin and nortriptyline were
      given in incremental doses at 2-weekly intervals till a maximum tolerated dose
      was obtained. The primary efficacy parameter was change in pain score (11-point
      Likert scale) from baseline to the end of the study period. RESULTS: 70 patients
      were available for intention-to-treat analysis. The average pain scores on the
      Likert scale were significantly reduced at the end of study in both the treatment
      groups with 47.6% and 42.8% reduction in pain scores in nortriptyline and
      gabapentin groups, respectively. Patients showed significant improvement in sleep
      scores in both the treatment groups nortriptyline (46.0%) and gabapentin (52.0%).
      The VAS and the SF-MPQ scores for pain were significantly reduced in both the
      groups. Gabapentin was, however, better tolerated as compared to nortriptyline.
      CONCLUSION: Gabapentin was shown to be equally efficacious but was better
      tolerated compared to nortriptyline and can be considered a suitable alternative
      for the treatment of PHN.

PMID- 16961167
TI  - Effect of ACE and AT-2 inhibitors on mortality and progression to
      microalbuminuria in a nested case-control study of diabetic nephropathy in
      diabetes mellitus type 2: results from the GENDIAN study.
AB  - INTRODUCTION: There is an established role of clinical risk factors such as
      arterial hypertension and smoking in causing cardiovascular morbidity and
      diabetic nephropathy (DNP). Genetic factors increase the risk for DNP. To examine
      the genetic risk, we initiated a case-control study with predefined follow-up
      examinations. We describe the study design and baseline characteristics under
      special consideration of comedication, and give preliminary results of the 4-year
      follow-up. METHODS: We enrolled all 477 patients with DNP receiving maintenance
      hemodialysis in 30 centers in Southern Germany between August 1999 and January
      2000. As controls, we enrolled all 482 diabetes mellitus type 2 patients without
      urinary microalbuminuria in two examinations on consecutive days and without
      other signs of renal disease in a large diabetes clinic from September 2000 to
      September 2001. Follow-up examinations are performed 4 and 6 years after
      inclusion by questionnaire and telephone interview to determine mortality and new
      morbidity. Controls progressing to novel DNP at follow-up, as defined by
      semiquantitative dipstick urinary albumin/creatinine ratio > 30 mg/g, are defined
      as cases in the study's nested case control component. RESULTS: At study
      inclusion in cases and controls, respectively, mean age was 67.3 +/- 8.2 and 58.1
      +/- 11.2 years and duration of diabetes mellitus was 15.6 +/- 9.6 (at dialysis
      initiation) and 11.0 +/- 8.6 years. 328 controls (of which 25 had died and 14 did
      not perform urinalysis) were subjected to follow-up at 4 years, at a mean of 3.5
      +/- 0.8 years after inclusion. 51.2% (n = 148) of living controls remained
      normalbuminuric, 33.9% (n = 98) had microor macroalbuminuria, and in 14.9% (n =
      43) the dipstick test was inconclusive. There was no significant difference in
      progression to micro- or macroalbuminuria between controls treated with ACE or AT
      2 inhibitors at baseline or not. Renal function as estimated by the abbreviated
      MDRD formula declined from 86.8 +/- 21.0 to 82.5 +/- 22.3 ml/min/1.73 m2 (p <
      0.001). The decline was significant in patients on ACE or AT-2 inhibitors at
      baseline and not in patients without such medication at baseline. DISCUSSION:
      GENDIAN is a large case-control study designed to evaluate clinical and genetic
      determinants of DNP and other complications of long-standing diabetes mellitus
      type 2. We observed an association of ACE or AT-2 inhibitor therapy with
      cardiovascular comorbidity and a significant decline in renal function after a 4
      year follow-up.

PMID- 16961168
TI  - Absorption characteristics of EC-MPS--an enteric-coated formulation of
      mycophenolic sodium.
AB  - Enteric-coated mycophenolate sodium is an advanced formulation delivering
      mycophenolic acid (MPA), designed to improve MPA-related upper gastrointestinal
      adverse events by delaying MPA release until the small intestine. OBJECTIVE: Two
      studies were undertaken to identify the absolute bioavailability and dose
      proportionality of enteric-coated mycophenolate sodium in stable renal transplant
      patients receiving cyclosporine. METHODS: Study 1: The mean MPA AUC(0-t) was
      shown to be greater after MPA infusion than after oral enteric-coated
      mycophenolate sodium (42.1 vs. 28.9 microg x h/ml). Mean absolute bioavailability
      was 0.71 +/- 0.21 (SD). Study 2: The AUC(0-t) and C(max) for MPA were
      proportional to the dose of enteric-coated mycophenolate sodium, similarly mean
      AUC(0-infinity) and C(max) for MPA glucuronide were proportional to dose
      administered. RESULTS AND CONCLUSIONS: In patients receiving cyclosporine the
      absolute bioavailability of MPA provided by enteric-coated mycophenolate sodium
      is equivalent to that provided by mycophenolate mofetil when administered in
      combination with cyclosporine, and exhibits dose-proportionality. Enteric-coated
      mycophenolate sodium was well tolerated from 180 - 2,160 mg with no serious
      adverse events reported.

PMID- 16961169
TI  - Pharmacokinetics and bioequivalence evaluation of two gabapentin preparations
      after a single oral dose in healthy Korean volunteers.
AB  - OBJECTIVE: To evaluate the bioequivalence of a single oral 400 mg dose of 2
      gabapentin preparations in healthy male Korean volunteers. SUBJECTS, MATERIALS
      AND METHODS: The study was conducted as a randomized, 2-period crossover design
      in 26 healthy male Korean volunteers who received a single oral dose of 400 mg
      gabapentin capsule in each study period. There was a 7-day washout period between
      the doses. Serum concentrations of gabapentin up to 24 hours after the
      administration were determined using a validated HPLC method with fluorescence
      detection. In addition, in vitro dissolution profiles of both preparations were
      examined. The pharmacokinetic parameters such as AUC(0.t) (the area under the
      curve from zero to the time), AUC(0-infinity) (the area under the curve from zero
      to infinity), C(max) (maximum serum concentration), t(max) (time to reach C(max))
      and t1/2 (terminal half-life) were analyzed by noncompartmental analysis, and the
      analysis of variance (ANOVA) was carried out using logarithmically transformed
      AUC(0-t), AUC(0-infinity) and C(max) and untransformed t(max). RESULTS: In vitro
      dissolution profiles were very similar at all media. There were no significant
      differences between the two preparations in AUC(0-t), AUC(0-infinity) and C(max).
      The point estimates (90% confidence intervals) for AUC(0-t), AUC(0-infinity) and
      C(max) were 1.0319 (0.9142 - 1.1647), 1.0127 (0.8458 - 1.2127) and 0.9796 (0.8670
      - 1.1069), respectively, satisfying the bioequivalence criteria of 0.80 - 1.25 as
      proposed by the US FDA and the Korean legislation. No statistically significant
      difference was found for tmax and t1/2 values. CONCLUSION: From the results of
      the present study, it is indicated that the two preparations of gabapentin are
      bioequivalent and it can be assumed that they are therapeutically equivalent and
      exchangeable in clinical practice.

PMID- 16961170
TI  - Use of promethazine in infants in primary care.

PMID- 16961171
TI  - A pharmacokinetic model of the gastrointestinal tract consisting of two segments
      can describe the concentration-time course of itraconazole.

PMID- 16961172
TI  - A new predictor of risk for sudden cardiac death.
AB  - BACKGROUND: Long-chain fatty acids, particularly omega-3 fatty acids found
      primarily in fish oil, are beneficial in different physiological conditions in
      the human body. High intake of omega-3 fatty acids has been found to have a
      strong inverse relationship to sudden cardiac death. An index showing the
      relationship between different fatty acids in the blood could be an important
      risk indicator for sudden cardiac death. METHODS: Whole-blood samples from the
      fingertip were collected and fatty acids were measured by a new simple method
      using direct transmethylation. Two groups were compared: subjects who had been
      taking fish oil daily during the last 6 years, and subjects who had not been
      taking fish oil. RESULTS: Six different fatty acid indices were calculated. Five
      of them take both DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) into
      consideration, and the sixth includes only EPA and not DHA in the calculation.
      This latter index, the ratio between EPA and arachidonic acid, gave the best
      result, with the largest difference between the two groups. This index varied
      between 5 and 118 among the different individuals; 70% of the fish oil consumers
      having an index > or =50. Based on the present knowledge about the relationship
      between blood levels of omega-3 fatty acids and sudden cardiac death obtained
      from studies of 14,000 individuals, a subject with an index below 50 should be
      advised to increase his/her intake of omega-3 fatty acids. CONCLUSION: The
      EPA/arachidonic acid index may be an important new predictor of risk for sudden
      cardiac death, and reflects the individual requirement for consumption of omega-3
      fatty acids.

PMID- 16961173
TI  - Risk group for hip fracture in elderly women identified by primary care
      questionnaire--clinical implications.
AB  - BACKGROUND: Every fourth Swedish woman suffers hip fracture during life-time.
      Several methods for fall and fracture prevention are known. In this study we
      identify women at high hip fracture risk in a primary care population, describing
      their needs for possible fracture prevention as well. METHODS: Cross-sectional
      questionnaire study for self-assessment by randomly chosen elderly women (n=100)
      over 70 years of age in a Primary health Care district at 1998. Questionnaire was
      designed from previous validated study. Follow-up study after three years
      performed at 2001. RESULTS: Response rate was 92% (n=92, mean age 78) and 90%
      (n=83) answered the main 40 questions. 30% had at least two of four major risk
      factors for hip fracture; age over 80 years, body weight below 60 kg, recent fall
      and previous fragility fracture. The recall ability for at least two of these
      four risk factors was 93% in follow-up study after three years (relative risk =
      8.0 with 95% confidence interval 3.5 to 18). 34% of the women had experienced any
      fracture since the age of 50. Only 22% of the women with previous fragility
      fracture had any pharmacological treatment for osteoporosis. 26% had falls in the
      preceding 12 months, mainly at home. Needs for fracture prevention were found in
      34% (27 women). CONCLUSIONS: Age, weight, recent falls or previous fragility
      fracture were common and important clinical risk factors for hip fracture with
      good recall ability after three years. By using this questionnaire in a Primary
      health Care district we identified women at high fracture risk. Needs for
      fracture prevention were observed for one third.

PMID- 16961174
TI  - Ropivacaine may have advantages compared to bupivacaine in porcine endotoxemic
      shock.
AB  - Patients that undergo major abdominal surgery often receive epidural
      postoperative analgesia. Septic complications are frequently seen in this cohort.
      In a porcine model of endotoxemic shock, resembling human gram-negative septic
      shock, we evaluated the effects of two widely used local anaesthetics,
      bupivacaine and ropivacaine given intravenously. In the endotoxin-ropivacaine
      group mixed venous saturation and platelet count were higher as compared to
      endotoxemic controls. Mean arterial blood pressure and platelet count were higher
      in ropivacaine-endotoxin pigs than in bupivacaine-endotoxin ones. Bupivacaine
      augmented endotoxin-mediated decrease in left ventricular stroke work index.
      Ropivacaine displays pathophysiological advantages compared to bupivacaine in
      septic shock, which may be explained by improved tissue perfusion by ropivacaine.

PMID- 16961175
TI  - External quality assessment of HbA(1c) for point of care testing.
AB  - OBJECTIVES: To evaluate the long term total imprecision of HbA(1c) testing within
      the county of Uppsala in relation to the Swedish analytical goal of coefficient
      of variation (CV) < 3% for HbA(1c) and to study the cost of an external quality
      assurance program for point-of-care HbA(1c) The county uses Bayer DCA 2000 for
      point-of-care HbA(1c) testing currently having 23 of these instruments. METHODS:
      Method imprecision was assessed by analysis of patient samples performed as split
      samples during a 3 year period (2002-2004) as part of the quality assurance
      program for point-of-care HbA(1c) testing. The samples were first analysed on a
      Bayer DCA 2000 and the samples were then sent to the centralised laboratory for
      reanalysis with an HPLC system (Variant II, Biorad). The testing was performed
      approximately 8 times per year with each instrument. RESULTS: The median CV
      between the HPLC method and the point-of-care instruments for each unit was
      slightly higher than 3%. CONCLUSION: The DCA 2000 systems have an acceptable
      imprecision and agreement with the central laboratory. The test results show
      acceptable agreements within the county regardless where the patient is tested.
      The cost of the external quality assurance program is calculated to be
      approximately SEK 1340 (Euro 150) per instrument.

PMID- 16961176
TI  - Evaluation of Dade Behring N Latex Cystatin C reagent on Abbott ci8200.
AB  - Plasma cystatin C has been shown in several studies to be superior to plasma
      creatinine for estimation of glomerular filtration rate (GFR). Reporting cystatin
      C results in mL/min using conversion formulas for transforming cystatin C
      expressed as mg/L to GFR expressed as mL/min has greatly facilitated the clinical
      use of the marker. At our hospital we have an increasing demand for cystatin C
      and at present we perform over 1400 cystatin C analyses a month. The test is
      available at all hours. This in combination with the volume emphasises the need
      to have the assay close to the routine chemistry instrument to reduce handling
      time per test and time to report test results. We have thus evaluated the Dade
      Behring N Latex Cystatin C assay (Dade Behring, Deerfield, IL, USA) on Architect
      ci8200 (Abbott Laboratories, Abbott Park, IL, USA). The nephelometric method on
      the ProSpec (Dade Behring) and the turbidimetric method on Architect ci8200
      showed very good agreement (y = 1.0072x + 0.0042; R2 = 0.987). Accordingly,
      running the cystatin C analyses on a chemistry instrument (Architect ci8200)
      would be proper to increase the availability of the analysis and reduce
      turnaround times.

PMID- 16961177
TI  - A morphometric study on the endometrium of rat uterus in hypothyroid and
      thyroxine treated hypothyroid rats.
AB  - Hypothyroidism increases the rate of pregnancy loss. Other manifestations include
      menstrual disorder, and infertility. Serum levels of gonadotropins are low in
      hypothyroid patients. Though studies of uterine ultrastructure are well
      established as approaches to investigating the pathophysiology of infertility,
      they have scarcely been extended to the study of hypothyroid related infertility.
      The present study investigates the effect of hypothyroidism on the ultrastructure
      of uterine epithelium. Three groups of Wistar rats were studied. Two groups were
      initially made hypothyroid using methimazole, and the third group was an
      untreated control. One hypothyroid group was given daily injections of thyroxine
      for six weeks. The uteri were removed in all three groups, and processed for
      transmission electron microscopy and morphometry. It was found that absolute
      epithelial cell volume was decreased in hypothyroidism. The volume of the nucleus
      had decreased though its relative volume in the cell had increased. The height of
      the luminal epithelium in hypothyroid rats also decreased by (33.8%) as compared
      with controls. Basement membrane thickness was significantly increased in
      hypothyroidism. The changes were all substantially abrogated by the
      administration of thyroxine. This study suggests that thyroid hormones might be
      importantly concerned in the maintenance of the normal structure of uterine
      epithelial cells.

PMID- 16961178
TI  - Malacoplakia and spermatic granuloma complicating vasectomy.
AB  - Malacoplakia is a granulomatous disease with a histiocytic infiltrate containing
      calcified structures called Michaelis-Gutmann bodies. These structures are
      considered to represent an abnormal response to infection involving defective
      lysosomes and abnormal microbubular assembly. The disease most frequently
      involves urinary and genital tracts, but has also been described from most other
      organs. Here we present the first case of malacoplakia only involving the vas
      deferens.

PMID- 16961179
TI  - Gene expression analysis of ectopic bone formation induced by electroporatic gene
      transfer of BMP4.
AB  - Implantation of bone morphogenetic protein (BMP) using a carrier or by BMP gene
      transfer into rodent muscle can induce bone formation. Implanted BMP becomes
      bioactive immediately after implantation. In BMP gene transfer, there is a time
      lag between the secretion of gene products and bone formation. We analyzed the
      gene expression of chondrogenic and osteogenic specific markers in the process of
      ectopic bone formation by using semi-quantitative RT-PCR. A plasmid vector
      containing mouse BMP4 gene (pCAGGS-BMP4) was transferred into the gastrocnemius
      muscles of mice using electroporation. Histological examination revealed the
      process of endochondral bone formation in the pCAGGS-BMP4 transferred muscles. As
      chondrogenic markers, aggrecan gene maximal expression was detected on day 7 and
      decreased by day 14, and for collagen X the gene maximal expression was on day
      10. As osteogenic markers, osteocalcin (OCN), bone sialoprotein (BSP) and
      osteopontin (OPN) gene expressions were clearly detected from day 10 and then
      increased by day 14. In conclusion, the present study proved that ectopic bone
      formation by BMP4 gene transfer into the muscle induced endochondral ossification
      that corresponded well with that to that by implantation of demineralized bone
      matrix.

PMID- 16961180
TI  - SAPHO syndrome with a tumour-like bony proliferative lesion in distal femur. A
      case report.
AB  - SAPHO syndrome is a group of bone and joint abnormalities associated with skin
      lesions. A 29-year-old male presented with severe acne on his trunk and anterior
      chest wall, right knee and foot pain. Radiographs and magnetic resonance images
      showed hyperostosis in the sternocostoclavicular region, sclerosis of one-third
      of the right distal 5th metatarsal bone and bony outgrowth from the medial
      condyle of the right femur. The histological findings of the biopsy specimen were
      consistent with-those of old osteomyelitis. All fungal and microbacterial
      cultures were negative. Pain and swelling of the right knee and foot repeated
      remission and aggravation. There were no radiological changes of the above
      mentioned lesions noted within 4-years follow-up.

PMID- 16961181
TI  - Ollier's disease treated with grafting using alpha-tricalcium phosphate cement. A
      case report.
AB  - Ollier's disease is a rare disorder characterized by multiple enchondromas with a
      unilateral predominance, especially in fingers in early childhood. We experienced
      a case of Ollier's disease treated four times with simple curettage from the age
      of 2 years and alpha-tricalcium phosphate cement grafting at the age of 21 years.
      The forth curettage was performed when the patient was 15 years old and
      preoperative X-rays had shown remarkable finger deformities. Postoperative
      casting of the involved joints was necessary to prevent fractures but led to some
      finger contractures. Following X-rays demonstrated incredible improvement of the
      appearance. This suggests that simple curettage alone at an early stage of
      Ollier's disease provide cosmetic improvement. At the age of 21 years our patient
      showed enlargement of the intramedullary finger lesions again. Some lesions
      seemed to be impending pathological fractures. This time we chose alpha
      tricalcium phosphate cement to fill the cavities after curettage had been carried
      out. Harvesting a large amount of autologous bone was not required. All
      activities of daily life could be resumed immediately after surgery and none of
      the finger joints showed further restriction of motion. X-rays taken three years
      after the operation showed new bone ingrowth surrounding the material with little
      evidence of absorption. To our knowledge, this may be the first case of Ollier's
      disease treated with artificial bone grafting reported in the English literature.

PMID- 16961182
TI  - Osteolipoma arising adjacent to the sternoclavicular joint. A case report.
AB  - A 45-year-old woman presented with one-year history of a mass on her chest.
      Computed tomography and magnetic resonance imaging demonstrated a tumour near the
      sternoclavicular joint. The tumour was diagnosed as osteolipoma histologically
      after resection. Osteolipoma is a rare tumour and this may be the first report of
      osteolipoma arising adjacent to the sternoclavicular joint.

PMID- 16961183
TI  - Ankle dislocation without accompanying malleolar fracture. A case report.
AB  - Dislocation of the tibiotalar joint without associated fracture is rare. We
      present here a 21-year-old man who sustained open posteromedial dislocation of
      the left ankle without malleolar facture when he jumped and sprained his right
      ankle while playing basketball. The most likely mechanism is forced flexion
      applied to the ankle joint leading to a rupture of the anterior capsule and
      lateral structures of the ankle followed by an accelerating inversion stress
      leading to a posteromedial dislocation of the talus from the tibial condyle.
      Transient paresthesia was noted in the area of the superficial peroneal nerve. At
      surgery, the anterior part of the tibiotalar joint capsule and anterior
      talofibular ligament were detached from their original sites. The calcaneofibular
      ligament was also detached with its associated periosteum and a tiny avulsed bony
      fragment. The articular facets of the tibia and talus were intact. The treatment
      consisted of wound irrigation, debridement, reduction and capsular suture
      followed by immobilization with a short leg cast. About 10 degrees of loss in the
      range of dorsiflexion was observed. The patient achieved good long-term
      functional results.

PMID- 16961184
TI  - Operative treatment by external fixation for polyostotic fibrous dysplasia in the
      elbow joint. A case report.
AB  - Fibrous dysplasia is a condition in which normal skeletal bone changes into
      fibroblastic stroma and immature bone. We report our experience of a unilateral
      external fixator applied for the treatment of polyostotic fibrous dysplasia
      arising in the elbow. The patient was a 38 year-old man. His main complaint was
      left elbow pain and a mass, which increased in size. The histological diagnosis
      from the needle biopsy was fibrous dysplasia. An articulated unilateral external
      fixator was used for immobilization. The lesions in the left distal humerus and
      proximal ulna were curetted and cancellous bone was packed into the cavity. An
      external fixator (Elbow Fixator, Orthofix Inc., McKinney, USA) was applied from
      the proximal humeral shaft to the distal ulnar shaft for postoperative tentative
      immobilization and preservation of the affected elbow joint movement. At two
      years after the operation, the range of motion of the affected elbow was 90
      degrees in flexion and -35 degrees in extension. The range of motion in pronation
      and supination of the left forearm was normal. No evidence of recurrence was
      noted at two years after surgery. The merits of using an external fixator were:
      an earlier start of range of motion exercises, and a decrease in the risk of
      tumor dissemination.

PMID- 16961185
TI  - Three-dimensional finite element stress and strain analysis of a transfemoral
      osseointegration implant.
AB  - The percutaneous transfemoral osseointegration implant is an alternative
      technique for direct prosthetic limb attachment. In order to investigate the
      stress and strain in the transfemoral osseointegration implant system, finite
      element (FE) analyses were carried out using three-dimensional femur-implant
      models and the commercial FE software ABAQUS. The three-dimensional femoral model
      was reconstructed from presurgery CT scans of an above-knee amputee. The implant
      was then inserted into the femoral model using Boolean operations in CAD
      software. Under a typical walking load, stress and strain from the femur-implant
      FE model were investigated. Stress concentrations were found near to the distal
      and proximal regions of the femur. To study the effect of different contact
      ratios between femur and implant, FE analyses were carried out using different
      implant diameters. The results showed that there were local stress variations
      near the contact discontinuity areas. A comparison was also made between the
      results of this study and a previous study using axisymmetric FE models. The
      results of the two studies revealed different stress levels, but good correlation
      was found in the overall stress distribution.

PMID- 16961186
TI  - Intraoperative knee anthropometrics: correlation with cartilage wear.
AB  - Accurate knee morphology is of value in determining the correct sizing of
      prosthetic implants. Intraoperative measurement of key linear dimensional
      variables was carried out on 196 Caucasian knees (osteoarthritic patients: 68
      male and 128 female). Of the 196 knees measured, 70 had extensive cartilage
      degeneration. Statistical analysis was carried out on this large sample size of
      data. Summary statistics and correlation coefficients between variables were
      determined and compared between subgroups. Male knees were on average larger than
      female knees. Higher correlation was found between variables for males than
      between variables for females. Overall, the patellar dimensions were seen to
      correlate least well with other anatomical variables. High correlation between
      femoral variables supports current femoral sizing procedure, although routine
      patellar resection practices are called into question. Average values for the 70
      knees with extensive cartilage degeneration were significantly smaller (P < 0.01)
      than their counterparts for the other 126 knees. For a measurement not containing
      cartilage, such as femoral epicondylar width, this difference cannot be accounted
      for by the loss of cartilage owing to wear. This suggests that, for similar
      height and weight, a naturally narrower femoral epicondylar width may be
      associated with severe osteoarthritis.

PMID- 16961187
TI  - The biophysical effects of a single impact load on human and bovine articular
      cartilage.
AB  - Impact injury to a joint is a known risk factor for the subsequent development of
      secondary osteoarthritis. An in vitro model, employing a drop-tower loading
      machine, was used to examine the effect of an impact load on isolated articular
      cartilage explants from human and bovine femoral heads. Two different types of
      impact experiment were performed. In the first, 4 mm diameter explants were
      loaded using a plane-ended impactor. In the second, a modified impactor was
      developed that had a central 4 mm diameter plane-ended indentor which was used to
      load the centre of 8 mm diameter explants. This enabled the unloaded outer ring
      of each explant to be compared with the loaded central core. The modulus values
      measured using the impactor were found to be higher, compared with the indentor
      in both species. Scanning electron microscopy showed that cartilage surrounding
      the loaded central region of the 8 mm explants protected the indented tissue, and
      these explants showed less damage than the 4 mm samples that were fully impacted.
      In addition, human cartilage was found to be less damaged than bovine, possibly
      as a consequence of the different structure as well as of a greater thickness.
      Both the source of the tissue and the nature of the impact affected the type of
      damage observed.

PMID- 16961188
TI  - The effects of proteins on the friction and lubrication of artificial joints.
AB  - The tribological testing of artificial hip and knee joints in the laboratory has
      been ongoing for several decades. This work has been carried out in an attempt to
      simulate the loading and motion conditions applied in vivo and, therefore, the
      potential for the success of the joint. However, several different lubricants
      have been used in these tests. The work documented in this paper compares results
      obtained using different lubricants and makes suggestions for future work. Hip
      joints and knee joints of different material combinations were tested in a
      friction simulator to determine their friction and lubrication properties. Both
      carboxymethyl cellulose (CMC) fluids and bovine serum (with CMC fluids added)
      were used as the lubricants. These were prepared to various viscosities to
      produce the Stribeck plots. Human synovial fluid, of just one viscosity, was used
      as the lubricant with some of the joints to give a true comparison with
      physiological lubricants. The results showed that, in most cases, the lubricant
      had a significant effect on the friction developed between the joint surfaces.
      This is thought to be due to the proteins that are present within the bovine
      serum adsorbing to the bearing surfaces, creating 'solid-like' films which rub
      together, protecting the surfaces from solid-to-solid contact. This would be
      beneficial in terms of wear but can either increase or decrease the friction
      between the contacting surfaces. It is important to simulate the conditions in
      vivo as closely as possible when testing these joints to try to obtain a better
      comparison between the joints and to simulate more accurately the way that these
      joints will operate in the body. In an attempt to simulate synovial fluid, bovine
      serum seems to be the most popular lubricant used at present. It would be
      beneficial, however, to develop a new synthetic lubricant that more closely
      matches synovial fluid. This would allow us to predict more accurately how these
      joints would operate long-term in vivo.

PMID- 16961189
TI  - Importance of head diameter, clearance, and cup wall thickness in
      elastohydrodynamic lubrication analysis of metal-on-metal hip resurfacing
      prostheses.
AB  - The main design features of metal-on-metal (MOM) hip resurfacing prostheses in
      promoting elastohydrodynamic lubrication were investigated in the present study,
      including the femoral head diameter, the clearance, and the cup wall thickness.
      Simplified conceptual models were developed, based on equivalent uniform wall
      thicknesses for both the cup and the head as well as the support materials
      representing bone and cement, and subsequently used for elastohydrodynamic
      lubrication analysis. Both typical first- and second-generation MOM hip
      resurfacing prostheses with different clearances and cup wall thicknesses were
      considered with a fixed large bearing diameter of 50 mm, as well as a 28 mm
      diameter MOM total hip replacement bearing for the purpose of comparison. The
      importance of the head diameter and the clearance in promoting elastohydrodynamic
      lubrication was confirmed. Furthermore, it was also predicted that a relatively
      thin acetabular cup in the more recently introduced second-generation MOM hip
      resurfacing prostheses would be capable of improving elastohydrodynamic
      lubrication even further.

PMID- 16961190
TI  - A pilot study in the application of texture relief for digitally designed facial
      prostheses.
AB  - This pilot research aims to identify and assess suitable technologies that may be
      used to capture, create, and produce fine textures and wrinkles that may be
      incorporated into computer aided prosthesis design and production techniques. A
      range of suitable technologies is identified and two methods that may be used in
      different prosthetic rehabilitation situations are assessed: the creation of
      three-dimensional relief in a computer aided design environment and the capture
      of facial anatomy and texture using fringe-projection surface scanning. Patterns
      were produced using the suitable rapid prototyping processes identified, and
      these were assessed by a qualified and experienced prosthetist. The suitability
      of the technologies is commented upon, limitations discussed, and future
      directions identified.

PMID- 16961191
TI  - Virtual reality and a haptic master-slave set-up in post-stroke upper-limb
      rehabilitation.
AB  - Since the number of stroke patients is ever growing, and since studies show that
      the patients can benefit from more exercise, the possible use of virtual reality
      and haptic devices in the rehabilitation of stroke patients is researched.
      Besides offering more independent and challenging exercise possibilities, the
      inherent registration capabilities of the haptic devices open up the possibility
      of monitoring patients' motions in an objective way. This research results in the
      implementation of a VR mock-up of an exercise in which patients use both hands
      and a stick to push away a ball that is tossed at them. In this mock-up, two FCS
      HapticMasters are used in a master-slave set-up to mimic the behaviour of the
      stick. The implementation of the scene shows that there are currently
      limitations, in the hardware as well as in the software, that cause the virtual
      exercise to behave differently to the real-life exercise. Consequences for the
      therapeutic value are subject to further research.

PMID- 16961192
TI  - Survive, help, learn: experience of a medical journal in war and post-war times.
AB  - Medical journals and their editors have a unique responsibility in armed
      conflicts. The experience of the Croatian Medical Journal during and after the
      1991-1995 war in Croatia shows how a medical journal can survive, help others and
      learn in times of war. The first duty of a medical journal in such circumstances
      is to publish scientific articles on various aspects of war medicine, and to
      document cases of human rights abuses. In small scientific communities, editors
      can offer their expertise and assist authors in writing and publishing war
      related research and reports. In post-conflict period, medical journals have a
      responsibility to participate in peace-building and reconciliation efforts. They
      can do so by publishing good scientific articles regardless of their place or
      country of origin, re-establishing contacts with colleagues from the opposing
      sides, striving for the multiethnic or multinational Editorial and Advisory
      Boards, and engaging in collaborative research and regional initiatives.

PMID- 16961193
TI  - Impact of war on the household environment and domestic activities: vital lessons
      from the civil war in Lebanon.

PMID- 16961194
TI  - Why does Sweden have the lowest childhood injury mortality in the world? The
      roles of architecture and public pre-school services.
AB  - Of interest is how some countries have achieved a profound reduction of child
      injury mortality. Still little is reported on the impact of a combination of
      urban planning, social welfare development and safety measures. We therefore
      present trends in childhood (0-14 years) injury mortality in Sweden 1966-2001 and
      discuss the factors behind any reductions observed. Annual total and cause
      specific injury mortality rates were computed by age subgroups and gender. Trend
      analyses were performed with year as independent and mortality rate as dependent
      variable. A piecewise linear function was fitted to the annual mortality rates.
      Data were categorized into five 7-year intervals. In total, there were 5264
      deaths due to injury in the study population during the period 1966-2001, of
      which 3368 (64%) were of boys and 1896 (36%) girls. The most frequent external
      cause of death was transport injury (48%), drowning (14%), homicide (5.8%), fire
      (5%), and fall (2.7%). About 66% (n=3474) of deaths occurred during the first
      half of the study period (1966-1981) with an average incidence rate of mortality
      13.0 compared to 5.6 per 100,000 inhabitants during the second half of the period
      (1982-2001). For total injuries, there was a statistically significant decrease
      in mortality among all subgroups of children in both sexes. The slopes are
      greater among the younger children (0-4, 5-9 years) than the older ones (10-14
      years). Several factors behind this strong decline of childhood injury mortality
      of interest to evaluate are (i) the implementation of the functionalist
      architectural style including transport separation, legislation and safety in
      cars; (ii) the expansion of public child day-care centers including more
      organized leisure activities; (iii) the establishment of long-term nationwide
      mandatory program for swim training among school children and (iv) local child
      safety programs considering differences in exposure to risk between urban and
      rural areas.

PMID- 16961195
TI  - The good news about smoking: how do U.S. newspapers cover tobacco issues?
AB  - Media advocacy, or advocacy seeking media attention, can shape the policy
      environment, but the relationship between the nature of news media coverage of
      public health topics and policy outcomes has received insufficient research
      attention. We present the first large-scale study of news coverage of tobacco to
      focus on the potential impact for policy outcomes. Through our analysis of 9859
      tobacco-focused news articles from ioo leading US daily newspapers between 2001
      and 2003 we examined whether tobacco issues are newsworthy, and if so, whether
      coverage is favorable to policy progress. We found strong evidence for news
      worthiness, and a tendency for coverage to highlight policy approaches to
      tackling tobacco. Coverage emphasized successes rather than setbacks, and
      newspaper editors lent support to tobacco control positions. There were, however,
      areas that did not garner sufficient attention to sustain a meaningful policy
      message. Our analysis of coverage of controversial issues also revealed areas
      where tobacco control efforts seem to pushing against ideological boundaries.

PMID- 16961196
TI  - Motor vehicle deaths: failed policy analysis and neglected policy.
AB  - The author of a recent book inferred that the slowed decline in U.S. vehicle
      fatality rates in the 1990 s relative to other industrialized countries resulted
      from too much emphasis on vehicle factors. He claimed that Canada had the same
      vehicle mix but a lower fatality rate. Actually, U.S. death rates by make and
      model applied to Canadian vehicle sales indicates that Canada's death rate would
      be the same as the U.S. if Canada had the same vehicle mix and annual miles
      driven. The U.S. had much greater growth in sales of large SUVs and pickup trucks
      that are heavier and stiffer than passenger cars, contributing to excess deaths
      of other road users in collisions. They are also more unstable, contributing to
      excess deaths of their occupants in rollovers. Lack of policy regarding these
      vehicle characteristics is the primary reason for the attenuated decline in
      vehicular fatality rates.

PMID- 16961197
TI  - In what direction is the Canadian healthcare system evolving?

PMID- 16961198
TI  - The publishing gap between rich and poor: the focus of AuthorAID.

PMID- 16961199
TI  - Thermal stability of penicillin G acylase : effect of stabilizing agents.
AB  - The role of sugars, polyhydroxy compounds, phenylacetic acid and 6
      aminopenicillanic acid in stabilization of immobilized penicillin G acylase
      (IMPGA) was studied. The loss in the activity of IMPGA at 50 degrees C, 2 h,
      after incorporation of sucrose and mannitol at 0.1 M concentration was 16 and 18%
      respectively; the loss in the activity of the enzyme under these conditions in
      the absence of stabilizing agents was 40%.

PMID- 16961200
TI  - Optimisation of nutritional requirements and process control parameters for the
      production of HA-2-91, a new tetraene polyene antibiotic.
AB  - HA-2-91, a new tetraene polyene antibiotic produced during submerged fermentation
      of Streptomyces arenae var ukrainiana. Optimisation of nutritional requirements
      and process control parameters were studied for higher productivity of HA-2-91
      during fermentative production in shaken flasks using complex media. Experimental
      findings indicate that jowar starch (Sorghum vulgare) is the best carbon source
      while cornsteep liquor in combination with peanut meal are the best nitrogen
      sources. Exogenous addition of amino acids, divalent cations and fatty acids
      suppressed the productivity of HA-2-91. Incorporation of glucose into the
      production medium above 5% (w/v) results in inhibition of productivity of HA-2-91
      which may be due to catabolite regulation. The concentration of phosphate ions
      above 10 ppm also showed similar suppression effect on the productivity of HA-2
      91. However, ferrous ions at 100 ppm showed slight stimulatory effect on the
      production of HA-2-91. The optimum process control parameters for the production
      of HA-2-91 were found to be temperature, 28 degrees C; inoculum concentration
      from seed to production medium, 1% (v/v); pH and volume of production medium 6.5
      and 100 ml respectively; and fermentation cycle time, 120 hours.

PMID- 16961201
TI  - Preliminary studies on production of extracellular lipase by an isolate from soil
      : Aspergillus flavus oryzae.
AB  - In our routine screening programme, using agar diffusion assay method, lipolytic
      activity was detected around a colony of a fungus. The fungus was isolated from a
      soil sample which was brought from a location near oil-mill. This lipolytic
      fungus was then identified to belong to Aspergillus flavus oryzae. A medium was
      then formulated and optimized which would not only support good growth but also
      would yield good extracellular lipolytic activity. It was observed that a
      conventional carbohydrate-protein containing medium supported good growth of the
      fungus but moderate lipase activity, whereas, a hydrocarbon containing medium,
      although supported relatively less growth, yielded much more lipase activity.

PMID- 16961202
TI  - Seed borne nature of Azotobacter chroococcum in chilli (Capsicum annum) and its
      role in seed germination and plant growth.
AB  - Investigations were carried out on seed borne nature of Azotobacter chroococcum
      in chilli and their role in plant growth at the Department of Agriculture
      Microbiology, University of Agricultural Sciences, Dharwad. Azotobacter
      chroococcum were isolated from both surface sterilized and unsterilized seeds of
      14 varieties of chilli at different stages of fruit maturity. Inoculation with
      these strains increased the seed germination, root, shoot length and total dry
      matter content of chilli plants significantly in both sterilized and unsterilized
      soil., the results of which are presented.

PMID- 16961203
TI  - A new streptomycete producing diphenyl sulfone antibiotic--S. sulfonensis.
AB  - About 359 actinomycetes were isolated from 8 different natural substrates
      collected from different parts of Andhra Pradesh. The isolates were screened on
      the basis of their inhibitory effect against test organisms. Finally one potent
      antibiotic producer was chosen having broad-spectrum activity against Gram
      positive and Gram-negative bacteria and it was found to produce a diphenyl
      sulfone antibiotic. On the basis of morphological, cultural, physiological and
      biochemical characters, the diphenyl sulfone antibiotic producer was identified
      as a new species and was designated as S. sulfonensis.

PMID- 16961204
TI  - Pharmacological evaluation of some bioactive plant products on albino rats.
AB  - The study comprises the pharmacological trials with essential oils of Caesulia
      axillaris, Ocimum gratissimum and Mentha arvensis which have shown strong
      antifungal property. The biochemical analysis of blood and serum of albino rats
      fed with the oil treated diet for sixty days exhibited nonanimal toxic nature of
      the oils. The study reveals the possibility of further exploitation of the oils
      as safe antifungal agents of plant origin.

PMID- 16961205
TI  - Exopolysaccharide production by some rhizobium strain in culture.
AB  - Eight Rhizobium strains were screened for exopolysaccharide production during
      growth in yeast extract mannitol medium. A strain of Rhizobium loti produced more
      than 250 mg of exopolysaccharide/100 ml of culture during the stationary phase of
      growth. Exopolysaccharide production was favoured by maltose and mannitol but N2
      supplementation could not affect the production siginificantly. Preliminary
      studies indicate that the polymer contains 16% protein and 73.5% carbohydrate
      being composed of glucose, galactose and glucuronic acid.

PMID- 16961206
TI  - ELISA using enzyme penicillinase for the detection of IgG antibodies to
      Trypanosoma evansi in sera of experimentally infected rabbits.
AB  - An Enzyme Linked Immunosorbent Assay (ELISA) using penicillinase as an enzyme
      marker has been developed for the detection of IgG antibodies in the sera of
      Trypanosoma evansi infected rabbits. Anti-T. evansi IgG antibodies were detected
      on 10th day after the infection and thereafter antibody titre rose progressively
      for 18 days. The developed assay is simple (end result assessed visually) and
      reproducible (4.4 and 14.0 percentage of intra and inter coefficient of variation
      respectively).

PMID- 16961207
TI  - Synthesis and antibacterial activity of some Schiff bases and 4-thiazolidinones.
AB  - Some new schiff bases (1a-d) 4-thiazolidinones (2a-d) have been synthesised and
      tested for their antibacterial activity. The structures of these compounds have
      been established on the basis of elemental analysis and spectral data (IR and H1
      NMR).

PMID- 16961208
TI  - Population dynamics of antibiotic producing actinomycetes from Avadh soils of U.
      P., India.

PMID- 16961210
TI  - [Photon avalanche upconversion in Er3+-doped telluride glass excited by 980 nm
      laser].
AB  - By laser excitation at the wavelength of 980 nm, efficient upconversion emission
      at 550 nm was observed in Er3+ doped telluride glass. The upconversion intensity
      varies nonlinearly with the excitation power with a threshold of 44 mW. The
      photon response time, of the order of tens of milliseconds, is much longer than
      the emission lifetimes. Moreover, the response time decreases with the increase
      in excitation power. The power dependence of the intensity and response time
      indicates that the green emission is generated through photon avalanche
      upconversion. Compared with 690 or 579 nm excitation wavelength, 980 nm is more
      efficient.

PMID- 16961209
TI  - Effect of some essential oils on microorganisms.
AB  - The essential oils tested viz., Cardiaca Oil, Mentha Oil, Artemisia Oil and
      Geranium Oil against pathogenic bacterial and fungal strains. Significant
      activity of all oils was found against all microorganisms. All the four oils
      showed a higher inhibition against all the microorganisms, except S. epidermidis
      at different level of concentrations used (1000 ppm and 500 ppm). It is clearly
      indicated that inhibition activity increased approximately 1 to 2 folds at 1000
      ppm concentration as compared to 500 ppm. S. epidermidis has shown resistant
      towards all the oils at both the concentration while M. smegmatis and S. mutans
      have shown higher inhibition as compared to S. epidermidis.

PMID- 16961211
TI  - [The fluorescence emission of water at upconversion of frequency by laser induced
      fluorescence].
AB  - The fluorescence spectra of several types of water samples in combination with
      laser-induced fluorescence (LIF) measurements using 532 nm wavelength excitation
      source were measured in the laboratory, and the fluorescence matters such as
      dissolved organic matter (DOM), chlorophyll a (Chl a) and carotenoids were
      pointed out with spectral fluorescent signature (SFS) technique. It is considered
      that the peak at 455 nm in the spectrum is contributed by carotenoid (PPC).
      Finally, the dynamic model of PPC's fluorescence emission is showed.

PMID- 16961212
TI  - [The preparation and spectroscopic characteristics of ytterbium silicate
      glasses].
AB  - Yb3+-doped silicate glasses were prepared at high temperature, which had a small
      non-linear refractive index coefficient n2 (1.62), lower transformation
      temperature and lower softening temperature (540 degrees C and 585 degrees C,
      respectively). The absorption spectrum from 850 to 1100 nm showed that the main
      peak was at 975 nm with two subpeaks near 908 nm and 944 nm, respectively.
      Emission peak was at 1,010 nm in the fluorescence spectrum with a 65.5 nm
      fluorescence half-line width. The integrated absorption cross section, stimulated
      emission cross section and fluorescence time were caculated to be 3.44 X 10(4)
      pm2, 0.71 pm2 and 1.05 ms, respectively, which satisfy the requirements of laser
      glasses.

PMID- 16961213
TI  - [The influence of frequency on solid state cathodoluminescence].
AB  - Solid state cathodoluminescence (SSCL) is a new mechanism of light emission in
      organic-inorganic system. In the present article, we get SSCL under sinusoidal
      alternating-current voltage with a structure of ITO/SiO2/MEH-PPV/SiO2/Al. The
      spectra have two peaks: 410 and 580 nm, which obey molecular theory and band
      model, respectively. The temporal behaviors of both peaks in SSCL are studied
      with a new method of estimating lifetime in frequency domain. The intensity of
      the peak at 410 nm decreases as the frequency of the driving voltage increases,
      and the intensity of the peak at 580 nm increases as the frequency of the driving
      voltage increases. The difference in the dependence of light intensity on the
      frequency of excitation comes from the difference in the lifetime of the two
      peaks. The lifetime of short wavelength emission is found to be less than 5 ms
      while that of long wavelength emission is more than 0.05 ms.

PMID- 16961214
TI  - [Study of spectral property of Er3+-doped TiO2].
AB  - Spectral property of Er3+-doped TiO2 prepared with gel method using absolute
      alcohol, glacial acetic acid and tetrabutyl titanate was studied. The Stokes
      emission spectra at 488 nm and upconversion emission spectra at 980 nm of the
      material were measured. In the visible range, green and red light was observed
      with green light corresponding to 2H(11/2), 4S(3/2)-->4I(15/2) transition of
      Er3+, and red light corresponding to 4F(9/2)-->4I(15/2) transition of Er3+. The
      green and red light are both two-phonon process from the curve of In Ivis-ln Iin,
      as the light intensity is directly proportional to the square of pump power.
      Elementary studies of the upconversion process were conducted.

PMID- 16961215
TI  - [The time-evolution study on the laser-induced oxygen plasmas spectra].
AB  - The present paper reports the results of spectroscopic study on the oxygen plasma
      induced by a pulsed laser with a wavelength of 1.06 microm. The gas samples were
      pure oxygen (99.9999%) and the spectral range was from 300 to 900 nm. The
      temporal behavior of the spectra was measured. The experiment results showed that
      the spectra could be divided into continuous spectra and line spectra. Each
      component of the spectra attenuated according to the disparate mode along
      temporal development. The microcosmic physical processes and mechanisms were
      analyzed. The reason for the longer plasma spectral lifetime was discussed. These
      works were helpful to better understanding of the microscopic mechanisms during
      the decay of the laser-induced air plasmas, and also provide more experimental
      evidences for prolonging the decay time of plasmas in some technical
      applications.

PMID- 16961216
TI  - [Spectral properties of carbazole molecules and three-photon induced lasing].
AB  - Spectral properties of a series of new heterocyclic molecules were studied in the
      present work. The spectral experimental results show that the two-photon
      absorption cross-sections of these new molecules are dependent on their charge
      transfer dipole moments, which relate to the donor acceptor end groups. At high
      density pumping, the spectral and temporal properties of the high directional
      emission of a new molecule with two-photon absorption cross-section of 617.3 GM
      demonstrate that three-photon induced lasing occurs.

PMID- 16961217
TI  - [2+1, 1+1 and 1+1+1 multiphoton resonant ionization of manganese atom].
AB  - Resonance ionization spectroscopy (RIS) is an important technique for trace
      analyses. In the present paper, based on the population rate equations, "2+1",
      "1+1" and "1+1+1" multiphoton resonant ionization processes of Mn atom are
      studied by computer simulation. The phenomena and the threshold condition of
      saturated excitation and ionization processes are discussed. The threshold laser
      intensities for saturated ionization of Mn atom with different RIS schemes are
      calculated. With the typical Q-switched laser duration of 10 ns, the obtained
      saturation threshold laser intensity for the ionization steps in all the resonant
      ionization processes of Mn is about 10(8) W x cm(-2) with the exception of the
      "1+ 1" resonant ionization of Mn which is 3 orders of magnitude lower. The
      obtained threshold laser intensity for the saturated excitation steps is about
      10(2)-10(3) W x cm(-2) in "1+1" and "1+1+1" ionization processes. It is also
      shown that the threshold laser intensity required for saturated excitation and
      ionization processes turns smaller with the laser duration prolonged.

PMID- 16961218
TI  - [Terahertz time-domain spectroscopic study of carbon monoxide].
AB  - Terahertz time-domain spectroscopy is a new coherent spectral technique based on
      femtosecond laser technology. The radiation band belongs to far infrared. This
      paper presents the absorption spectra of carbon monoxide measured by terahertz
      time-domain spectroscopy in the frequency range between 0.2 and 2.5 THz. The
      experimental results indicate that the carbon monoxide has many distinct
      characteristic spectra between 0.2 and 2.5 THz which agree with the calculated
      results. The absorption peaks become sharper with decreasing the pressure. This
      work establishes the basic spectra data for the future identification and
      characterization of carbon monoxide, and it is very significative to measure the
      harmful substance in the atmosphere by terahertz technology.

PMID- 16961219
TI  - [The analysis of vibrational structure of the electronic spectra of diatomic
      molecules].
AB  - On the basis of the spectrum term of a electronic rotational-vibrational energy
      level, the law of vibrational band sequences and progressions in diatomic
      molecules was analysed. According to the law, the Deslandres table and its nature
      were summarized. How to indicate the measured values of a electronic-vibrational
      spectrum was illustrated by taking the Swan band spectra of the C2 molecule as an
      example. In the example, the measured values were put in order which formed the
      Deslandres table in terms of the law of vibrational structure. The authors can
      gain some important data, such as anharmonicity constants and harmonic oscillator
      frequencies in different vibrational states, concerning the band spectra of
      molecules. Furthermore, the formula of wave numbers of every band spectrum was
      derived.

PMID- 16961220
TI  - [The study of infrared background radiation of earth and atmosphere by airborne
      FTIR spectrometer].
AB  - The present article describes the experiment of airborne Fourier transform
      infrared (FTIR) spectrometer detecting the background radiation of earth and
      atmosphere. Considering the surface radiation and atmospheric absorbance and
      emission, the expression of radiations measured by airborne FTIR is given. It is
      indicated that the background radiations depend on four parameters: surface
      temperature, surface emissivity, atmospheric transmission and temperature. Based
      on theoretic analysis the measured spectra are compared and analyzed according to
      the differences in altitude and surface. Spectral characters of infrared
      background radiation are described.

PMID- 16961221
TI  - [FTIR and thermal analysis study of GAP and GAP/B].
AB  - The thermal decomposition of GAP and GAP/B in air and nitrogen were studied by
      FTIR and TG-DTG. The analysis by FTIR and TG-DTG shows that the azide group
      elimination reactions of GAP begin at about 170 degrees C and finish around 250
      degrees C, and the depolymerization of GAP delays by 40 degrees C; Boron changes
      the mechanism of thermal decomposition process of GAP, and the results show that
      GAP/B starts losing mass between 55 and 70 degrees C, which is much earlier than
      GAP itself does. Furthermore, the depolymerization of GAP almost takes place at
      the same temperature with the azide group elimination. Some kinetics parameters
      of the reactions were calculated based on Kissinger's processing methods. The
      results show that the activation energies of the thermal decomposition of GAP and
      GAP/B are lower and the reactions are easier to occur under air. The possible
      reason is that the oxygen containing thermal decomposition of GAP has happened.

PMID- 16961222
TI  - [Study on real-time control of extraction procedure of Furitus gardenia by near
      infrared spectroscopy].
AB  - A new approach to the real-time control of extraction procedures based on fiber
      optic near infrared spectroscopy (NIR) was described. Various extraction samples
      of gardenia were rapidly scanned by NIR, and the SIMCA monitoring model was
      developed. The model was applied to evaluate the extraction procedures of 26
      unknown samples, and all the samples from abnormal procedures were successfully
      identified. It is suggested that near infrared spectroscopy, combined with SIMCA
      method, is a rapid, convenient and efficient tool for real-time procedure
      monitoring, which needs no quantitative determination and can effectively monitor
      whether the current procedure is in normal or not. The presented approach,
      therefore, offers a new way for the quality control in real-time of traditional
      Chinese medicine.

PMID- 16961223
TI  - [Study on near-infrared absorption mechanism of alkali lignin].
AB  - The results showed that o-quinone and q-quinone had strong absorption while
      vanillin had nearly no absorption in the 800-900 nm range of near-infrared
      spectroscopy through the comparison of their near-infrared absorption spectra. It
      was proved that quinone structure of alkali lignin had strong absorption in the
      800-900 nm range of near-infrared spectroscopy. The change in the absorbency of
      oleander milled wood lignin treated with NaOH and Na2 S before and after is
      greater than that in the absorbency of ginkgo milled wood lignin treated with
      NaOH and Na2 S before and after because more quinone structure was formed in the
      process of oleander milled wood lignin treated with NaOH and Na2 S. The finding
      well explained that cooking liquor of hardwood was much stronger than that of
      softwood while their pulp kappa number was very near.

PMID- 16961224
TI  - [Near infrared spectroscopy of wood sections and rapid density prediction].
AB  - In the present report, the use of calibrated near infrared (NIR) spectroscopy for
      rapid prediction of solid wood density is described. NIR spectra were obtained
      from the three sections (cross, radial and tangential section) of each Chinese
      fir sample. The authors found that the spectra of the three sections are
      different and the correlation coefficients between the laboratory-determined
      density and the NIR-fitted data are different, too. The prediction results showed
      that the model based on NIR spectra taken from the cross section is the best, and
      the correlation coefficients are 0.94 (cross), 0.85 (radial) and 0.81
      (tangential), respectively. Using the cross model to predict the density of
      unknown wood samples, we can see: r2 is 0.977 and the standard deviation (STDEV)
      is only 0.006.

PMID- 16961225
TI  - [Detection of pear firmness using near infrared diffuse reflectance
      spectroscopy].
AB  - The objective of the present research was to study the potential of NIR diffuse
      reflectance spectroscopy as a way for nondestructive measurement of the firmness
      of "Xueqing" pear. NIR spectral data were collected in the spectral region
      between 800 nm and 2,630 nm, but only the data between 800 nm and 2,500 nm were
      used for the analysis. Spectral data smoothing of different gaps using Savitsky
      Goaly method was discussed both qualitatively and quantitatively. The results
      showed that the smoothing of NIR original spectra had little influence on
      spectral data analysis. Statistical models were developed using partial least
      square method. Models for three kinds of mathematical treatments of spectra
      (original, first derivative and second derivative) were established in three
      spectral regions: 800-2,500 nm, 800-1,890 nm and 832-872 nm. The original spectra
      showed better results than the first derivative spectra and second derivative in
      all the three spectral regions. And for the three spectral regions, the full
      wavelength range of 800-2,500 nm offered the best result. The PLS model of
      original spectra in the range of 800-2,500 nm gave best predictions of pear
      firmness, with correlation coefficient (r) of 0.869 and root mean square errors
      of calibration (RMSEC) of 3.88 N for the calibration sample set and with
      correlation coefficient (r) of 0.840 and root mean square error of prediction
      (RMSEP) of 4.26 N for the validation sample set. The results of the study show
      that NIR diffuse reflectance specroscopy can be used to predict the firmness of
      "Xueqing" pear.

PMID- 16961226
TI  - [Study on the wax enhancement for the unearthed jade wares by FTIR technique from
      ancient tombs of Shang-Zhou period in Henglingshan site of Boluo county Guangdong
      Province].
AB  - The ancient tombs of Henglingshang site in boluo county are the most significant
      graveyard site of Shang-Zhou period in Guangdong province as yet. Based on a
      series of scientific studies on the jade samples from these tombs, the authors
      found that there are 2-3 characteristic peaks at 2,960 cm(-1) (quite poor), 2,920
      and 2,853 cm(-1) in the infrared spectra. According to the tests and analyses of
      the infrared spectra of pure waxes and other modern jade wares treated with wax,
      the authors believe that these unearthed jade wares were enhanced with wax and
      the ancestors of Lingnan region in Shang-Zhou period (1600B.C.-221 B.C.) probably
      understood treating jade wares with wax to enhance their appearance.

PMID- 16961227
TI  - [Rapid and robust partial least squares regression and its application to NIR
      spectroscopy analysis].
AB  - Modern near infrared spectroscopy (NIRS), as an indirect analytical technique, is
      used to carriy out quantitative analysis of unknown samples by establishing a
      model with calibration samples. Taking into account the low sensitivity and poor
      disturbance rejection of NIRS, a new robust version of the SIMPLS algorithm was
      constructed from a robust covariance matrix for high-dimensional data and robust
      linear regression in the present paper. Because SIMPLS was based on the empirical
      cross-covariance matrix between the response variables and the regressors and on
      linear least squares regression, the results were affected by abnormal
      observations in the data set. In order to eliminate their negative impact on the
      accuracy and reliability of the model, a simple multivariate outlier-detection
      procedure and a robust estimator for the covariance matrix were embedded in the
      SIMPLS regression framework, based on the use of information obtained from
      projections onto the directions that maximize and minimize the kurtosis
      coefficient of the projected data. Finally, application of the proposed kurtosis
      SIMPLS method to the NIR analysis was presented with a comparison to the SIMPLS.
      The results show that kurtosis-SIMPLS method not only finds out the very outliers
      from the data set with less computational cost, but also holds better prediction
      performance and steady capability for the normal samples.

PMID- 16961228
TI  - [The characteristic IR spectra of microcystin-LR].
AB  - The IR spectra of mincrocystin-LR (mLR) were studied by Fourier transform
      infrared spectroscopy in the scanning range of 4,000-600 cm(-1). The
      characteristic IR spectra from main function groups such as monosubstituted
      benzene, guanidine residues and gamma-carboxylic groups etc have been identified.

PMID- 16961229
TI  - [The IR spectra of complexes of 2-hydroxy-2-ferrocenylpropylamine with Ni(II),
      Cu(II), Zn(II), Cd(II) and Hg(II)].
AB  - alpha-Cyano-alpha-ferrocenylethoxytrimethylsilame was prepared by the addition of
      trimethysilyl cyanide to acetylferrocene. 2-Hydroxy-2-ferrocenylpropylamine(FcA)
      was synthesized by the reduction of alpha-cyano-alpha
      ferrocenylethoxytrimethylsilame with lithium aluminum hydride. A series of
      coordinate complexes--FcA-Ni(II), FcA-Cu(II), FcA-Zn(II), FcA-Cd(II) and FcA
      Hg(II) were obtained through coordination of this ligand with MCl2 (M= Ni, Cu,
      Zn, Cd and Hg). The FTIR spectra of the complexes and ligand were obtained in the
      range of 4 000-400 cm(-1). Their major bands were assigned and compared. The
      results showed that in all complexes some bands(upsilonO-H, upsilonN-H sigmaO-H,
      sigmaN-H) were shifted to lower wave number, and some(upsilonC-N, upsilonO-N)
      were shifted to higher wave number. The aminoalcohol groups and metal ions were
      bound with coordinated bond.

PMID- 16961230
TI  - [Novel application of FTIR to the analysis of sweet pepper seeds and tomato seeds
      with space mutation].
AB  - Comparative study of the sweet pepper and tomato seeds lines with space mutation
      and corresponding conventional seeds was carried out with FTIR, in an attempt to
      search for the influence of space environment upon mutation. The similarities
      among space seeds lines are: the absorbance at near 1,160-1,061 cm(-1) increased.
      This result shows that the stretching vibration of C-O on the structure of
      carbohydrates was enhanced by space mutation. The special mutations are: (1) The
      absorbance at 2,854 cm(-1) of space sweet pepper was enhanced, showing that the
      stretching vibration of CH2 was stronger; (2) The absorbance at 1,160 cm(-1) of
      cherry tomato seeds lines was increased notably, indicating that the stretching
      vibration of C-O on the structure of carbohydrates was stronger. The results show
      that the space environment could notably increase the carbohydrates in the tomato
      seeds. The space sweet pepper and tomato seeds lines, which produced similar
      mutation, could be influenced by microgravity in space. The special mutations are
      the results of the influence of universe radiation in space.

PMID- 16961231
TI  - [Analysis and characterization of fingerprint infrared spectra for ecology
      planted Coptis chinensis].
AB  - The fingerprint features of infrared spectra for Coptis chinensis in different
      shading conditions (shelf, firry wood, corn wood) and with different ages (one
      year to five years) were studied. According to the ratio of characteristic peaks,
      the rules of the influence of shadings and ages on Coptis chinensis growth were
      illustrated, which confirms the feasibility of ecological planting technique for
      Coptis chinensis. Fourier transform infrared (FTIR) spectroscopy was used to
      analyze the influence of growing conditions on the growth of Coptis chinensis.
      The shadings and ages have no obvious influence on the quality of Coptis
      chinensis root, which is consistent with the results of HPLC. The quality of
      Coptis chinensis with ecological planting is identical with those in shelves.
      Infrared technique provides a meaningful guide to standardized planting of
      medicinal plants.

PMID- 16961232
TI  - [Surface-enhanced Raman spectra and electrochemical studies on the inhibition of
      nickel corrosion by imidazole].
AB  - Surface-enhanced Raman scattering (SERS) spectrum of imidazole adsorbed on a
      nickel electrode in 0.1 mol x L(-1) KCl solution was investigated as a function
      of applied potential. The corrosion inhibition effects of imidazole on the nickel
      electrodes in 0.1 mol x L(-1) KCl solution were investigated by using both cyclic
      voltagram and Tafel plot. The results indicated that imidazole was adsorbed on Ni
      electrode with tilted or perpendicular orientation due to the maximum enhancement
      of the in-plane vibration modes. The appearance of the peak at 1,173 cm(-1) (i.
      e. NH deformation) further supported the adsorption of neutral imidazole
      molecules in a neutral solution. A low-wave number band appeared at 214 cm(-1)
      was assigned to the Ni-N stretch, considering the interaction between imidazole
      molecules and the metal surface via N-atom. The molecules had maximum adsorption
      at -1.3 V. At higher negative potentials, the adsorption decreased gradually,
      which resulted in weaker inhibition effect.

PMID- 16961233
TI  - [A comparative Raman study of carbon nanotubes allays].
AB  - A series of comparative Raman study of carbon nanotubes arrays prepared by
      thermal chemical vapor deposition are reported. The results suggest that the G
      mode and D mode of carbon nanotubes (CNTs) arrays are all downshifted as compared
      to that of polycrystalline graphite, and the shifted number in well-aligned CNTs
      arrays is more than that in misaligned CNTs arrays. Moreover, the intensity ratio
      ID/IG indicates the ordering in CNTs arrays. A lower ID/IG means a higher
      graphitization and less amorphous carbon in CNTs arrays.

PMID- 16961234
TI  - [Fuzzing pattern recognition study on Raman spectrum of tumor peripheral tissue].
AB  - On the basis of some theories about fuzzing pattern recognition, the present
      article studied the data preprocessing of the Raman spectrum of tumor peripheral
      tissue, and feature extraction and selection. According to these features the
      authors improved the leaning towards the bigger membership function of
      trapezoidal distribution. The authors built the membership function of Raman
      spectrum of tumor peripheral tissue which belongs to malignant tumor on the basis
      of 40 specimens, and designed the classifier. The test of other 40 specimens
      showed that the discrimination of malignant tumor is 82.4%, while that of
      beginning tumor is 73.9%.

PMID- 16961235
TI  - [A new method for concentration determination of crude oil sample using three
      dimensional synchronous fluorescence spectra].
AB  - In the spectral investigation of crude oil samples, it has been found that the
      synchronous fluorescence spectra (SFS) of the crude oil sample varied with the
      concentration in both the intensity and the location of peaks. Considering the
      information about both the changes in SFS, a new method for the concentration
      determination of crude oil sample using three-dimensional synchronous
      fluorescence was developed and introduced in the present paper. A number of
      samples have been investigated to verify the feasibility of the method. The
      concentration of each sample has been determined with a deviation under 3% in the
      concentration range from 10(-4) to 1.0 g x L(-1). All the results suggest that
      the newly developed method may become an useful means in petroleum logging.

PMID- 16961236
TI  - [Quantum chemistry study on fluorescence spectra of three flavonoid compounds].
AB  - A theoretical study on three flavonoid compounds by semi-empirical method is
      presented in the present paper. Their geometric configurations were optimized by
      the semi-empirical method RHF/PM3. For all the optimal configurations, there is
      no imaginary frequency in vibrational analyses. On this basis, the electronic
      spectra were calculated by CIS method. All the calculated results are basically
      consistent with experimental values.

PMID- 16961237
TI  - [Fluorescence and resonance scattering spectral properties of TiO2 nanoparticle
      in water phase].
AB  - Nanometer-sized TiO2 sol was prepared by a microwave high-pressure method using
      terabuty titanate (TBTi) as a precursor, and was contrasted with the one prepared
      by Ti(SO4)2 hydrolysis method. Fluorescence and resonance scattering spectral
      properties of TiO2 nanoparticles prepared by the two different precursors were
      considered. The one using TBTi as precursor exhibits a resonance scattering peak
      at 320 nm, a synchrotron scattering peak at 470 nm, and three fluorescence
      emission peaks at 350, 400 and 470 nm, respectively. The other one prepared by
      Ti(SO4)2 has a resonance scattering peak at 340 nm, a synchrotron scattering peak
      at 470 nm, and two fluorescence emission peaks at 400 and 470 nm, respectively.
      Influences of the reaction conditions on the resonance scattering intensity are
      consistent with those on the fluorescence, but the resonance scattering intensity
      is stronger than the fluorescence intensity.

PMID- 16961238
TI  - [Resolution of synchronous fluorimetric spectrum for carbaryl and coumaphos and
      its application study].
AB  - The synchronous fluorimetric method for the simultaneous determination of
      carbaryl and coumaphos is described. In the Britton-Robinson buffer at pH 3.0,
      synchronous scanning with deltalambda= 60 nm was carried out, and the overlapped
      fluorimetric spectra were better separated. The two synchronous fluorimetric
      peaks are located at 280 and 322 nm respectively, and can be used for the
      determination of these two pesticides. No preliminary separation is needed. The
      method is simple, rapid and successfully applied to the analysis of food samples.
      The linear ranges of the calibration curves for carbaryl and coumaphos are 0.016
      0.384 microg x mL(-1) and 0.016-0.320 microg x mL(-1), respectively. The limits
      of detection are 0.015 microg x mL(-1) for carbaryl, and 0.010 microg x mL(-1)
      for coumaphos.

PMID- 16961239
TI  - [A new fluorescence quenching method for the determination of trace ClO2 in water
      using silver nanoparticles].
AB  - In pH 9.1 NH4Cl-NH3 x H2O buffer solution, there is a fluorescence peak at 470 nm
      for silver nanoparticles. A fluorescence quenching takes place when it was
      oxidized by ClO2. The intensity of fluorescence quenching is linear with the
      concentration of ClO2 in the range of 0.0011-0.185 microg x mL(-1). The detection
      limit is 0.004 7 microg x mL(-1). A new fluorescence method has been proposed for
      the determination of ClO2 in water samples with satisfactory results.

PMID- 16961240
TI  - [Study on fluorescence spectral behavior of trimethoxyphenylflurone with gallium
      in microemulsion].
AB  - In the present paper, the fluorescence spectral behavior of gallium with
      trimethoxyphenylflurone (TM-PF) in microemulsion was studied. In the buffer
      medium of HAc-NaAc at pH 4.95, the fluorescence intensity is in proportion to the
      concentration of gallium (III) in the range of 0-0.045 microg x mL(-1). The CTMAB
      microemulsion was efficiently used to enhance the sensibility and stability of
      the system, and the limits of detection were 1.2 ng x mL(-1). The coexistent
      metal ions can be separated and gallium can be enriched by the extraction of
      butyl acetate, greatly improving the selectivity and sensibility of the system.
      The method possesses high sensitivity as well as high selectivity. It can be used
      to determine trace amount of gallium in ore samples successfully.

PMID- 16961241
TI  - [Study on surface-capped CdS nanoparticles as fluorescence probes].
AB  - In the present paper, CdS nanoparticles of different size surface-capped with
      thiourea [expressed as CdS/SC(NH2)2] were prepared by sol-gel method, and
      characterized by XRD, TEM, IR and PL. The results show that the molar ratio of
      thiourea to cadmium ion has influence on the size and luminescence properties of
      the nanoparticles. With increasing the mdar ratio of thiourea to cadmium ion in
      the reactant, the size of the nanoparticles decreases, and the maximum emission
      wavelength of the nanoparticles shows an obvious blue shift due to quantum
      confinement effect. The effect of calf thymus deoxyribonucleic acid (ct-DNA) on
      the fluorescence spectrum of the CdS/SC(NH2)2 nanoparticles was also studied. The
      result shows that the intensity of fluorescence spectrum of the nanoparticles is
      quenched by ct-DNA, which is probably caused by the electrostatic interaction
      between CdS/SC(NH2)2 nanoparticles and ct-DNA. The CdS/SC(NH2)2 nanoparticles are
      hopeful of being used as fluorescence probes in DNA determination.

PMID- 16961242
TI  - [Synthesis and spectroscopy of K7[P2Mo4W13M(H2O)O61] (M= Cr, Fe) and their
      organic composite materials].
AB  - The Dawson heteropoly complexes K7[P2Mo4W13M(H2O)O61] (M= Cr(1), Fe(2)) and their
      organic composite materials formed by (E)-N-butyl-4-(2-(4'
      dimethylaminophenyl)ethenyl)pyridinium cation and compound 1 (or 2) with the
      stoichiometry of (C19H25N2)(6)K3[P2Mo4W13MO62](M=Cr(3), Fe(4)) were synthesized
      and characterized by elemental analyses, thermogravimetric and differential
      thermal analyses, and IR, UV-Vis, solid diffuse reflectance UV-Vis-near IR, X-ray
      photoelectron and fluorescence spectroscopy. The results of spectra show that
      compounds 1 and 2 have Dawson structure, inorganic-organic composite materials
      are formed between the hemicyanine cations and the heteropoly anions, and the
      charge transfer occurs from the hemicyanine cations to the heteropoly anions in 3
      and 4 complexes. The interaction between the hemicyanine cations and the
      heteropoly anions in the solid powder is stronger than that in the fluid
      solution. The compounds reported in this paper are interesting as nonlinear
      optical materials.

PMID- 16961243
TI  - [The change in optical spectra from solid and liquid solution of copper
      phthalocyanines derivatives].
AB  - In the present work, the change in electronic absorption spectra from three
      copper phthalocyanines (CuPc, tb-CuPc, oo-CuPc) in different environments was
      investigated. The mechanism of red shift Q-band absorption from the three species
      in an organic solvent before and after protonation was discussed. This was used
      to compare with those dispersed in solid films. The relation between the
      molecular interactions and the spectra change was studied. In a combination of
      POM, DSC and XRD techniques, the structure and morphology of the thin films were
      characterised. It was found that the molecules in the doped matrices of PC were
      associated or aggregated. This association and hence the corresponding change in
      absorption spectra cannot be altered by the modification of dopant concentration.

PMID- 16961244
TI  - [Synthesis and spectral properties of a new europium strontium oxide SrEu2O4].
AB  - A new europium strontium oxide was synthesized by high-temperature solid state
      reaction of SrCO3 with Eu2O3 in air. The new multiple oxide was characterized by
      use of XRD, TG/DTA and fluorescence spectra. The XRD results show that the
      molecular formula of the europium strontium oxide is SrEu2O4, whose structure is
      isostructural with that of BaEu2O4 reported earlier. The excitation spectrum of
      SrEu2O4 displays a broad double peaks band with one peak around 257 nm and the
      other around 280 nm. This broad band is attributed to the charge transfer
      transition of Eu3+-O2- bonds. Excited with a radiation of 280 nm, SrEu2O4 emits
      strong red light which is assigned to the 5D0-->7F2 electric dipole transition of
      Eu3+.

PMID- 16961245
TI  - [Hydrothermal synthesis of Co9S8 nanocrystalline aggregations and spectral
      study].
AB  - Co9S8 nanocrystalline aggregations were synthesized in hydrazine hydrate (N2H4 x
      H2O) solvent at 180 degrees C for 12 h through a hydrothermal method using cobalt
      sulfate hydrate (CoSO4 x 7H2O) and sodium sulfate (Na2SO3) as the starting
      materials. The prepared samples were characterized using X-ray diffraction (XRD),
      field-emission scanning electron microscope (FE-SEM), and transmission electron
      microscope (TEM). FTIR spectrum was measured using Fourier-transform infrared
      spectrometer. The results showed that the products were mainly composed of Co9S8
      hexagonal flakes, which were about 2.1 microm in diameter and 200 nm in
      thickness. The flakes consisted of Co9S8 nanocrystallites with an average size of
      2.5 nm.

PMID- 16961246
TI  - [Extraction and spectral properties analysis of innoxious ultraviolet
      absorbents].
AB  - Some dozens of ultraviolet absorbents were extracted from leaves of pure natural
      plants, such as frangipani, mango, and sweet-scented osmanthus. Then the spectral
      properties of these ultraviolet absorbents were analyzed. The plant that has the
      best effect of absorbing ultraviolet ray was selected by comparing one with the
      others. And the method of extracting ultraviolet absorbent was studied. The
      results showed that the method, which used leaves of mango as material, distilled
      water as extracted solvent, and alcohol as precipitator, was satisfactory. When
      the concentration of ultraviolet absorbent solution is 1% (w/w), the ultraviolet
      ray transmission is smaller than 1% in 200-400 nm. The rate of production is
      1.5%. It is innoxious.

PMID- 16961247
TI  - [Study on spectral properties of tri-functional polymers containing terbium
      complex].
AB  - In the present paper, a kind of tri-functional polymer containing terbium complex
      was synthesized. The spectral properties were studied by means of FTIR, UV-Vis,
      and TOF-SIMS. The results indicated that the polymer contained the oxadiazole
      group, carbazole group and terbium complex. The fluorescence property was
      investigated in different states. In solution, the spectra consisted of the
      emission band from the pi-->pi* transition of the oxadiazole and carbazole group
      and the emission peaks from the transitions between the 4f states of terbium. In
      solid state, the emission from the oxadiazole and carbazole group was suddenly
      suppressed, and the result also indicated that the efficiency of energy transfer
      in the solid state is much higher than that in solution. The polymer emits pure
      green light under the UV light in solid state.

PMID- 16961248
TI  - [The influence of temperature change on determined concentrations of dissolved
      organic matter in water].
AB  - The influence of temperature change on the determined concentrations of dissolved
      organic matter (DOM) in water was investigated by laser induced fluorescence
      (LIF) technique in laboratory. The temperature was altered within the range of 20
      to 75 degrees C, and the intensity of DOM fluorescence and water Raman scattering
      were found to decrease with rising temperature. A linear fit of the normalized
      fluorescence intensity versus temperature yielded a mean value of the temperature
      coefficient of -5.24 x 10(-4) x degrees C(-1), and a mean value of the
      temperature coefficient of -3.42 x 10(-3)(mg x L(-1)) x degrees C(-1) was
      obtained according to the relationship between normalized fluorescence intensity
      and concentration of DOM. The temperature change will cause relative changes of
      up to 8.45% in DOM concentration within the range of 20 to 75 degrees C if we
      assume that the normalized fluorescence intensity remains the same.

PMID- 16961249
TI  - [Reaction mechanism of cefotaxime with human serum albumin].
AB  - The reaction mechanism of cefotaxime with human serum albumin (HSA) and the
      affinity between cefotaxime and beta-lactamase were investigated by spectrometry
      and spectrofluorimetry. The interaction dissociation constants of human serum
      albumin and cefotaxime were determined from a double reciprocal Lineweaver-Burk
      plot. The binding distance and transfer efficiency between cefotaxime and HSA
      were also obtained according to the theory of Forster non-radiation energy
      transfer. The result suggested that the main binding force between cefotaxime and
      HSA is electrostatic force interaction. The high beta-lactamase stability of
      cefotaxime may be correlative with its molecular structure. The antibiotic
      activity and valence are connected with transfer efficiency and dissociation
      constant. The effect of cefotaxime on the conformation of HSA was also analyzed
      using synchronous fluorescence spectrometry.

PMID- 16961250
TI  - [Preparation and structural characterization of ZnTHPP/TiO2 hybrid material].
AB  - Using sol-gel method to make tetra-meso (hydroxylphenyl) zinc porphyrin (ZnTHPP)
      trapped in inorganic networks of TiO2, a new organic/inorganic hybrid material
      was prepared. The structures and morphology of this material were characterized
      by thermogravimetric analyses (TGA), infrared spectrum (FTIR), UV-Vis spectrum
      (UV), diffuse reflectance spectroscopy (DRS), and scanning electron microscopy
      (SEM), indicating that ZnTHPP/TiO2 hybrid material possessed excellent
      thermostability, and ZnTHPP was trapped in TiO2 network with chemical bonds. In
      addition, ZnTHPP embedding can enlarge the absorption range of light for TiO2
      effectivelly.

PMID- 16961251
TI  - [Synthesis and spectral characterization of rare-earth-3-hydroxyl-2-naphthalinate
      phenanthroline compounds].
AB  - The solid rare-earth (RE=Tb, Eu, Sm, Nd) compounds with 3-hydroxyl-2-naphthalinic
      acid (L) and phenanthroline (phen) were synthesized in ethanol solution in the
      present work. Their compositions were determined to be REL4 x phen2 x Na x H2O by
      the element analysis, infrared and ultraviolet absorption spectra, and DTA-TGA,
      respectively. The spectral properties of the compounds were studied tentatively,
      and the coordination mode of carboxyl group was deduced to be bridged style to
      chelate the rare-earth and sodium ions to form an infinite chain structural
      complex. The sodium and rare-earth ions are six-coordinated and eight-coordinated
      geometry respectively.

PMID- 16961252
TI  - [Study on the oxidation of solutions of aniline and phenol on Ti/SnO2-Sb2O5
      electrode by UV-Vis spectroscopy and HPLC].
AB  - The electrocatalytic oxidation and degradation of phenol and aniline were studied
      at Ti/SnO2-Sb2O5 electrode by UV-Vis spectroscopy and high performance liquid
      chromatography (HPLC). It is shown that hydroquinone, benzoquinone and maleic
      acid are the same intermediates and products during oxidation of both aniline and
      phenol. This indicates that the oxidation of the two compounds probably has the
      same degradation routes. The electropolymerization of anilines results in
      different oxidation and degradation course of aniline and phenol.

PMID- 16961253
TI  - [Synthesis of N'1, N'2-Bis[(1E)-(2-hydroxyphenyl)methylene]- ethanedihydrazide
      and its application to determination of Zn(II)].
AB  - A reagent of N'1,N'2-bis[(1E)-(2-hydroxyphenyl)methylene]ethanedihydrazide (DSOD)
      was synthesized, and characterized by IR spectra and element analysis. A highly
      sensitive fluorimetric method for the determination of trace amounts of zinc was
      proposed based on the reaction of Zn2+ with DSOD in ethanol at pH 7.00. The
      linear range of the method was 0-65.0 microg x L(-1) with a detection limit of
      0.30 microg x L(-1). The interferences of 16 common ions were investigated and
      the results showed that the DSOD had a good selectivity. The analytical results
      of detecting trace amounts of Zn2+ in zinc rich salt and hair by this method were
      satisfactory.

PMID- 16961254
TI  - [Spectrophotometric determination of chondroitin sulfate with victory blue B].
AB  - In pH 4.0 acetic acid-sodium acetate buffer solution, cationic dye victory blue B
      shows an absorption peak at 614 nm, and the absorption peak decreases after it
      reacts with chondroitin sulfate to form association particles. The decrease in
      absorption value is linear with chondroitin sulfate concentration in the range of
      0. 1-5 microg x mL(-1), and the correlation efficient is 0.9986. The method was
      applied to the determination of chondroitin sulfate in synthesis samples and real
      samples with rapidity, simplicity and good accuracy.

PMID- 16961255
TI  - [Rate of controlled-release urea pervasion through membrane determined by
      ultraviolet spectrophotometry].
AB  - Application of controlled-release nitrogenous fertilizers can improve the
      efficiency of fertilizers and reduce the environmental pollution. Controlled
      release urea (coated urea) is one of the controlled-release nitrogenous
      fertilizers developed quickly in the recent years. The rate of controlled-release
      urea pervasion through membrane is the most important index of the capacity of
      controlled release. There is a maximum absorption at lambda=426 nm with complex
      in acidic solution, using p-dimethylaminozenzaldehyde as color reagent, and the
      absorbance exhibits a linear reponses to the urea concentration over the range of
      7.5-210 microg x mL(-1). The method for determining the rate of controlled
      release urea pervasion through membrane was realized through determining the
      content of urea in the liquor, the recovery efficiency of the method is 96.1%
      103.9%.

PMID- 16961256
TI  - [Determination of trace elements in Niuhuang Jiedu tablets by microwave digestion
      and ICP-AES].
AB  - Niuhuang Jiedu tablets were digested with HNO3-H2O2 system by microwave
      digestion. The fourteen trace elements of As, Ca, Mg, Al, Mn, Sr, Ba, Se, Ni, Cd,
      Cu, Zn, Mo and Pb in the solution were determined by ICP-AES. The ICP-AES result
      proved to be reliable by adding standard recovery experiment to the process. By
      comparison with the result of chemical experiment, thr present method was
      accurate, quickly-accessible, and convenient. It was used for Niuhuang Jiedu
      tablets with result satisfactory.

PMID- 16961257
TI  - [Chip-based capillary electrophoresis on-line coupled with atomic fluorescence
      spectrometry and its application to rapid speciation analysis].
AB  - Chip-based capillary electrophoresis (chip-CE) is under rapid progress due to its
      high efficiency, fast separation, little sample consumption and integration. Due
      to the short optical path (30-50 microm), the conventional UV absorbance cannot
      satisfy the chip detection needs. Atomic fluorescence spectrometer (AFS) is a
      selective and sensitive detector for hydride-forming elements. With the strong
      points of low cost and easy operation, AFS is attractive as an ideal detector of
      chip-CE for mercury, arsenic and selenium, etc. A few important practical aspects
      of coupling chip-CE to AFS are critically discussed. These include the design of
      the chip, chip-AFS interface, gas-liquid separator, AFS atomizer, and elimination
      of the effect of backpressure on separation. The application of the developed
      chip-CE-AFS to the mercury speciation analysis is highlighted.

PMID- 16961258
TI  - [Precipitation trapping with phenylfluorone and determination of trace gallium,
      germanium, molybdenum and indium by GFAAS].
AB  - The preconcentration of trace gallium, germanium, molybdenum and indium by
      trapping with precipitation of phenylfluorone (PF), and the determination of the
      elements by GFAAS were developed. The effects such as those of acidity, amounts
      of PF, aging time, volume of test solution, and the coexistent ions on the
      preconcentration of the trace elements were examined in detail. The optimum
      conditions of preconcentration for Ga(III) were pH approximately 2 test solution
      500 mL with added 10.00 mg x mL(-1) PF (2.00 mL) and aging for 4 h, those for
      Ge(IV) were pH approximately 2 test solution 500 mL with added 10.00 mg x mL(-1)
      PF (4.00 mL) and aging for 10 h, those for Mo(V) were pH approximately 3 test
      solution 1 000 mL with added 10.00 mg x mL(-1) PF (3.00 mL) and aging for 6 h,
      and those for In(III) were pH approximately 5 test solution 100 mL with added
      10.00 mg x mL(-1) PF (3.00 mL) and aging for 10 h. The experiment results showed
      that the main contribution to trapping trace gallium, germanium, molybdenum and
      indium with PF precipitation was post-precipitation instead of coprecipitation.
      The detection limits (3s) were 0.12 ng x mL(-1) for gallium, 0.30 ng x mL(-1) for
      germanium, 0.046 ng x mL(-1) for molybdenum and 2.7 ng x mL(-1) for indium. The
      developed methods were successfully applied to the determination of trace amount
      of the elements in water samples, geological standard reference materials, and
      zinc concentrate samples by graphite furnace atomic absorption spectrometry.

PMID- 16961259
TI  - [Determination of As, Pb, Sn, Sb and Bi in high temperature iron and nickel-based
      alloy by graphite furnace atomic absorption spectrometry combined with liquid
      liquid extraction].
AB  - A method was developed for the determination of As, Pb, Sn, Sb and Bi in high
      temperature iron and nickel-based alloy by graphite furnace atomic absorption
      spectrometry combined with liquid-liquid extraction. These elements formed
      complexes with I- ions and were subsequently extracted into MIBK to be separated
      from matrix elements. The effects of remnant matrix elements were studied in
      detail. Meanwhile, the interferences of other elements, such as W, Nb and Ta,
      were eliminated with masking method. The recovery rates for As, Pb, Sn, Sb and Bi
      are in the range of 93%-99%, and the relative standard deviations are from 8.8%
      to 12%.

PMID- 16961260
TI  - [Determination and analysis of trace element manganese and amino acids content in
      aloe tea].
AB  - The content of trace element manganese in aloe tea was determined by atomic
      absorption spectrophotometry. The contents of 17 kinds of amino acids in aloe tea
      were determined with amino acids instrumentation. The results showed that there
      are comparatively rich manganese and amino acids in aloe tea. The content of
      manganese in red tea is more than in green tea, and the dissolving ratio is more
      than 50% in boiled water, and first dissolving ratio is more than second
      dissolving ratio, which is more than third dissolving ratio. There are 7 kinds of
      amino acids essential to human body, among which are comparatively high aspartic
      acid, glutamic acid and leucine in aloe tea. It's outstanding characteristic is
      comparatively high content of manganese in aloe health tea. It has provided
      useful data for probing into the relationship between trace elements and amino
      acids in aloe health tea and health care function.

PMID- 16961261
TI  - [Determination of six metal elements in plant Bupleurum scorzoneri folium Willd.
      by flame atomic absorption spectrophotometry (FAAS)].
AB  - The objective in this paper was to determine the amount of metal elements in the
      Plant Bupleurum scorzoneri folium Willd. by flame atomic absorption
      spectrophotometry (FAAS). FAAS method was established for the determination of
      Ca, Mg, Fe, Cu, Zn and Pb in the Plant Bupleurum scorzoneri folium Willd. after
      digestion with HNO3-HClO4 (V : V= 4 : 1) at 90-95 degrees C and at normal
      pressure. In the meantime, the optimum parameters of FAAS and the effects of
      solution medium on the results were studied. The analytical results of Ca, Mg,
      Fe, Cu and Zn were 5,588.9, 1,790.5, 869.3, 78.4, 44.3 microg x g(-1)
      respectively, and Pb was not checked out in the samples. The results showed that
      the recovery of standard addition was 99.57%-102.10%, the relative standard
      deviation (n= 9) was 0.18%-2.26%. The method is quick, simple and convenient, and
      the results are satisfactory.

PMID- 16961262
TI  - [Classification and application principles of optical-fibre transducer].
AB  - One of the new transducers is optical-fiber transducer, which has a wideying
      application prospect. The present paper describes the principles, classifications
      and advantages of the fiber sensor, and also reports the basic features and the
      outline of the application of the fiber sensors in types of intensity, phase and
      polarization modulation.

PMID- 16961263
TI  - [Linear scanning analysis of prehistoric human bones in Xigongqiao Site,
      Tengzhou, Shandong Province by use of SEM-EDS].
AB  - Ancient human bones in Xigongqiao Site, Tengzhou, Shandong Province, were
      analyzed by use of SEM-EDS. SEM indicated that the microstructure of Haversian
      system was destroyed under the impact of bone diagenesis. The apparent difference
      in elemental distribution in the bone cross section showed that the enrichment or
      loss of elements can occur not only in the inner and outer surface, but also in
      the middle. This study will have great influence on how to deal with the ancient
      human bones before any palaeodietary research in the future.

PMID- 16961264
TI  - Expression of recombinant baculovirus carrying Schistosoma japonicum 26 ku GST in
      mammalian cells.
AB  - In order to construct recombinant baculovirus carrying Schistosoma japonicum 26
      ku glutathione S-transferase gene (Sj26), and observe the expression of Sj26 in
      mammalian cells, the Sj26 gene was amplified with plasmid pGEX-3X as template by
      PCR, and then recombined into T vector for sequencing. Sj26 gene was inserted
      into the downstream of CMV promoter of donor plasmid pFBDGC, and the recombinant
      donor plasmid pFBDGC-Sj26 transformed into DH10Bac, then the recombinant bacmid
      AcCMVSj26 was isolated and transfected into Sf9 cells. The recombinant
      baculovirus was harvested and final titer of vAcCMVSj26 was measured. BHK cells
      were transducted with recombinant baculovirus in vitro. By using Western blot,
      the expression of 26 ku glutathione S-transferase (GST) was detected. The results
      showed that after enzyme digestion and sequencing, the donor plasmid was
      successfully constructed. PCR confirmed that pFBDGC-Sj26 and Bacmid homologous
      recombination occurred in E. coli. After transfection of Sf9 cells with
      recombinant Bacmid, recombinant baculovirus was replicated in Sf9 cells and
      expressed green fluorescent protein. PCR further revealed recombinant baculovirus
      contained Sj26. The titer of the harvested baculovirus was 1.24 x 10(8). Western
      blot demonstrated that recombinant baculovirus could express 26 ku GST in BHK
      cells. It was concluded that Sj26 recombinant baculovirus was successfully
      constructed, and the 26 ku GST was expressed in mammalian cells.

PMID- 16961265
TI  - Effect of electroacupuncture on reperfusion ventricular arrhythmia in rat.
AB  - Protective effect and mechanism of electroacupuncture (EA) on acute reperfusion
      ventricular arrhthmia was investigated. Ventricular arrhythmia was induced by
      occlusion of the proximal left anterior descend (LAD) branch of coronary artery
      for 5 min and followed with 15 min reperfusion. EA on acupoint "Neiguan",
      "Jianshi" was performed at 30 min before ligation and continued another 5 min
      during ischemia. Isoprenaline (20, 30 and 50 microg/kg) or atropine (1 mg/ kg)
      was intravenously injected at 5 min before ischemia. The results showed that EA
      significantly decreased the incidence of ischemia/reperfusion (I/R) induced
      ventricular tachycardia (VT), ventricular fibrillation (VF) and mortality as
      compared to I/R group. Atropine partially suppressed the EA's effect of
      antiarrhythmia; Isoprenaline increased the incidence and severity of reperfusion
      arrhythmia, which was inhibited by EA, but this inhibition of EA was blocked with
      increasing dose of isoprenaline. The results indicated that EA treatment could
      prevent the occurrence of reperfusion ventricular arrhythmia in rats with
      myocardial ischemia, and its mechanism might be related to the regulation of EA
      on the beta-adrenoceptors and M-cholinergic receptor activation in myocardium.

PMID- 16961266
TI  - Effect of truncated-ApoE4 overexpression on tau phosphorylation in cultured N2a
      cells.
AB  - The carboxyl-terminal amino acids 272-299-truncated apoE4 (delta272-299) is the
      main fragments of apoE4 hydrolysate in neurons. The effects of truncated-ApoE4
      (delta272-299) overexpression on tau phosphorylation in cultured N2a cells were
      investigated. The truncated-apoE4 (delta272-299) cDNA was subcloned into pEGFP-c3
      to form recombinant pEGFP-T-apoE4. pEGFP-c3, pEGFP-T-apoE4 and pEGFP-apoE4 were
      transfected into N2a cells respectively by lipofectamine 2000 method. After 24-
      48 h, tau phosphorylation was detected by Western blot assay and glycogen
      synthase kinase-3 (GSK-3) activity by using GSK-3 activity assay. The results
      showed that the overexpression of both full length-apoE4 and truncated apoE4
      fragments in N2a cells induced a dramatic increase in phosphorylation of tau at
      Ser202 sites and the activation of GSK-3 as compared with untransfected cells,
      most significantly in the cells transfected with pEGFP-T-apoE4 (P < 0.05). It was
      concluded that in vitro overexpression of truncated-ApoE4 (delta272-299) can
      result in tau hyperphosphorylation in N2a cells by activating GSK-3, suggesting
      truncated-ApoE4 (delta272-299) might contribute the pathogenesis of Alzheimer
      disease.

PMID- 16961267
TI  - Different effects of capsaicin on I(A) and I(K) in pain-conduct neurons of rats.
AB  - The different effects of capsaicin on I(A) and I(K) currents in pain-conduct
      neurons of trigeminal ganglia (TG) were investigated. In cultured TG neurons of
      rats, whole-cell patch clamp techniques were used to record the I(A) and I(K)
      before and after capsaicin perfused. Results revealed that 1 micromol/L capsaicin
      could inhibit the amplitude of I(A) by 48.2% (n = 10, P < 0.05), but had no
      inhibitory effect on I(K) (n = 7, P > 0.05). Ten micromol/L capsaicin could
      significantly inhibit the amplitude of I(A) by 93.2% (n = 8, P < 0.01), but only
      slightly inhibit the amplitude of I(K) by 13.2% (n = 7, P < 0.05). Neither 1
      micromol/L nor 10 micromol/L capsaicin had effects on the active curve of I(A)
      and I(K). It was concluded that capsaicin could selectively inhibit the I(A)
      current, and this effect might involve in the analgesic mechanisms of capsaicin.

PMID- 16961268
TI  - Evaluation of 99mTc labeled diadenosine tetraphosphate as an atherosclerotic
      plaque imaging agent in experimental models.
AB  - The potential of 99mTc labeled P1, P4-di (adenosine-5')-tetraphosphate (Ap4A) for
      imaging experimental atherosclerotic plaques was evaluated in New Zealand white
      (NZW) rabbits. To label the 99mTc to Ap4A, stannous tartrate solution was used.
      99mTc-Ap4A was purified on a Sephadex G-25 column. The radiochemistry purities of
      99mTc-Ap4A were 85% to 91%. Biodistribution study revealed 99mTc-Ap4A cleared
      from blood rapidly. Thirty min after 99mTc-Ap4A administrated on NZW
      atherosclerotic rabbits, lesion to blood (target/blood, T/B) ratio was 3.17 +/-
      1.27, and lesions to normal (target/non-target, T/NT) ratio was 5.23 +/- 1.87.
      Shadows of atherosclerotic plaques were clearly visible on radioautographic film.
      Aortas with atherosclerotic plaques also could be seen on ex vivo gamma camera
      images. Atherosclerotic abdominal aortas were clearly visible on in vivo images
      15 min to 3 h after 99mTc-Ap4A administration. 99mTc-labeled Ap4A can be used for
      rapid noninvasive detection of experimental atherosclerotic plaque.

PMID- 16961269
TI  - Detection of ischemic myocardium with a new hypoxic tissue targeting tracer
      99Tc(m)-HL91.
AB  - The imaging appearances of 99Tc(m)-HL91, a new hypoxic imaging agent, in ischemic
      myocardium were studied and the value of 99Tc(m)-HL91 in the evaluation of
      regional ischemic viable myocardium was explored. Acute myocardial ischemia
      models were made by coronary artery legations in 18 rats and randomly divided
      into 2 groups: 99Tc(m)-HL91 group and 99Tc(m)-MIBI group. Evan blue infusion
      during ischemia and TTC staining after operation were used to delineate the area
      of ischemic and viable myocardium. The isolated heart was sliced in the short
      axis and then autoradiography was performed. The electron microscopic examination
      was also done for the myocardial samples. 99Tc(m)-HL91 and 99Tc(m)-MIBI uptake
      activities (counts/g) were measured in the area of ischemic myocardium (T) and
      normal myocardium (NT) separately. The uptake ratios of 99Tc(m)-HL91 and that of
      99Tc(m)-MIBI in ischemic myocardium were calculated as T/NT. It was found that
      the normal myocardium was blue and ischemic or infarct myocardium was negative
      with Evans blue in all experiment rats. Both the normal and ischemic myocardium
      was in red color with TTC staining. In the 99Tc(m)-HL91 group the ischemic
      myocardium showed much higher uptake over normal myocardium, that was
      demonstrated both in the autoradiography and quantitative analysis. The
      ischemic/normal activity ratios were 1.634 +/- 0.354. It was suggested that
      99Tc(m)-HL91 might accumulate in ischemic and viable myocardium, which is helpful
      in the evaluation of hypoxic but viable myocardium and potentially used as a
      imaging agent to assess myocardial viability.

PMID- 16961270
TI  - Effects of insulin treatment on intracellular lipid metabolism in liver of
      diabetic rats.
AB  - The effects and the mechanism of insulin treatment on intracellular lipid
      metabolism in liver of diabetic rats were evaluated. Type 2 diabetic rats were
      induced by injecting the streptozotocin (25 mg/kg) and fat rich food. According
      to the results of oral glucose tolerance test (OGTT) and glucose-induced insulin
      secretion test (IRT), the rats were divided into two groups: untreated group (UT)
      and insulin-treated group (IT). Normal rats (NC) served as controls. The
      treatment with either Humulin N (4--6 U/kg every day), or saline lasted for 4
      weeks. Body weight, OGTT, IRT, blood lipids, intracellular lipids in liver,
      hepatic fatty acid oxidation and the activity of fatty acid synthase (FAS) were
      detected. The change of liver histology was observed. The insulin sensitivity
      index (ISI) was applied to assess the status of insulin resistance. The results
      showed that as compared with NC group, the plasma and hepatic intracellular
      Triglyceride (TG), total cholesterol (TC) and free fatty acids (FFAs) were
      increased significantly in UT group (P < 0.05), and lipid droplets could be seen
      dispersedly in the liver specimens, the hepatic fatty acid oxidation was
      increased markedly (P < 0.05), while the fatty acid synthase activity decreased
      (P < 0.05). Insulin treatment resulted in a further accumulation of lipids in
      liver by 55.7%, 19.87% and 22.2% increase in TG, TC, FFAs respectively. The size
      of hepatocytes was enlarged and the cells were filled with fat drops. Plasma
      lipids showed little decrease and still significantly higher than those in NC
      group after the insulin treatment. Meanwhile, insulin treatment was companied by
      20% decrease in the rate of fatty acid oxidation and 31% increase in hepatic FAS
      activity compared to UT group. It was concluded that treatment with insulin on
      type 2 diabetic rat increases hepatic intracellular lipid accumulation by
      inhibiting hepatic fatty acid oxidation and activating FAS.

PMID- 16961271
TI  - Expression of resistin protein in normal human subcutaneous adipose tissue and
      pregnant women subcutaneous adipose tissue and placenta.
AB  - The expression of resistin protein in normal human abdominal, thigh, pregnant
      women abdominal, non-pregnant women abdominal subcutaneous adipose tissue and
      placenta and the relationship between obesity, type 2 diabetes mellitus (T2DM),
      pregnant physiological insulin resistance (IR) and gestational diabetes mellitus
      (GDM) was investigated. The expression of resistin protein in normal human
      abdominal, thigh, pregnant women abdominal, non-pregnant women abdominal
      subcutaneous adipose tissue and placenta was detected by using Western blotting
      method. Fasting serum glucose concentration was measured by glucose oxidase
      assay. Serum cholesterol (CHOL), serum triglycerides (TG), serum HDL cholesterol
      (HDL-C) and serum LDL cholesterol (LDL-C) were determined by full automatic
      biochemical instrument. Fasting insulin was measured by enzyme immunoassay to
      calculate insulin resistance index (IRI). Height, weight, systolic blood pressure
      (SBP) and diastolic blood pressure (DBP) were measured to calculate body mass
      index (BMI) and body fat percentage (BF %). Resistin protein expression in
      pregnant women placental tissue (67 905 +/- 8441) (arbitrary A values) was much
      higher than that in subcutaneous adipose tissue in pregnant women abdomen (40 718
      +/- 3818, P < 0.01), non-pregnant women abdomen (38 288 +/- 2084, P < 0.01),
      normal human abdomen (39 421 +/- 6087, P < 0.01) and thigh (14 942 +/- 6706, P <
      0.001) respectively. The resistin expression in abdominal subcutaneous adipose
      tissue showed no significant difference among pregnant, non-pregnant women and
      normal human, but much higher than that in thigh subcutaneous adipose tissue (P <
      0.001). Pearson analysis revealed that resistin protein was correlated with BMI
      (r = 0.42), fasting insulin concentration (r = 0.38), IRI (r = 0.34), BF % (r =
      0.43) and fasting glucose (r = 0.39), but not with blood pressure, CHOL, TG, HDL
      C and LDL-C. It was suggested that resistin protein expression in human abdominal
      subcutaneous adipose tissue was much higher than that in human thigh subcutaneous
      adipose tissue. Resistin was closely related with central obesity, leading to IR,
      subsequently obesity and T2DM. Resistin protein expression in placental tissue
      was much higher than that in subcutaneous adipose tissue in normal human abdomen,
      pregnant abdomen, non-pregnant women abdomen and thigh. It was indicated that
      resistin protein could be secreted from human placental tissue. Resistin might be
      one of the factors that lead to pregnant physiological IR and GDM.

PMID- 16961272
TI  - Effects of mycophenolic acid on high glucose-induced expression of TGF-beta and
      CTGF in mesangial cells.
AB  - The effects of mycophenolic acid (MPA) on high glucose-induced expression of
      transforming growth factor-beta (TGF-beta) and connective tissue growth factor
      (CTGF) in mesangial cells (MC) were investigated. Rat MC were cultured in the
      presence of different concentrations of MPA (1.0 and 10.0 micromol/L) or MPA plus
      high glucose for 72 h. The expression of TGF-beta and CTGF was detected by
      Western blot. The results showed that high glucose could induce the expression of
      TGF-beta and CTGF in MC, but MPA could inhibit this effects. MPA did not
      influence the expression of TGF-beta and CTGF in normal glucose. It was concluded
      that MPA might prevent the progression of diabetic nephropathy by inhibiting the
      expression of TGF-beta and CTGF in MC.

PMID- 16961273
TI  - A potential pathological role of angiopoietins expression in glomeruli during
      progressive glomerulisclerosis related to podocyte injury.
AB  - A potential pathological role of angiopoietins (Ang) in glomeruli following
      podocyte injury-induced progressive glomerulosclerosis was explored. Eighty male
      Wistar rats were randomly allocated into sham operation group (Sham, n = 25),
      Uninephrectomy group (UPHT, n = 25) and Uninephrectomy+Daunorubicin group (DRB, n
      = 30). In DRB group, daunorubicin (5 mg/kg) was injected via tail vein on the 7th
      and 14th day after uninephrectomy. At week 1, 2, 4, 6 and 8 respectively
      following establishment of the animal model, 5 rats in Sham group and UPHT group,
      and 6 in DRB group were taken respectively for determining 24-h urinary protein
      excretion rate (24hUPER), blood urea nitrogen (BUN) and serum creatinine (Scr).
      The sections of kidneys were examined by an electric microscope, PAS staining,
      immunohistochemical staining and in situ hybridization histochemistry. The
      results showed that 24hUPER, BUN and Scr in DRB group were more than those in
      Sham group and UPHT group at the same time points, and there was a trend towards
      an increase on level of GSI in DRB group from week 2 to week 8. Electric
      microscopy revealed that podocyte injury presented in DRB group. The expression
      of Ang1 mRNA and protein in glomeruli of DRB group was decreased, while the
      expression of Ang2 protein in glomeruli of DRB group increased. Meanwhile, the
      expression of Ang1 mRNA had a negative correlation with the expression of Ang2
      mRNA, and the expression of Ang1 protein had a positive correlation with the
      expression of Ang1 mRNA, and had a negative correlation with 24hUPER, BUN, Scr,
      glomerular sclerotic index (GSI), the expression of Ang2 protein and CoIV
      protein. The expression of Ang2 protein had a positive correlation with the
      expression of Ang2 mRNA, and had a positive correlation with 24hUPER, BUN, Scr,
      GSI, the expression of CoIV protein. It was concluded that podocyte injury might
      lead to an alteration in the expression of Ang1 and Ang2 within glomeruli. Ang2
      may get rid of inhibition from Ang1 for downregulation of the Ang1 expression,
      which facilitate upregulation of the Ang2 expression in glomeruli to promote
      progressive glomerulosclerosis in the rats.

PMID- 16961274
TI  - Establishment of stable high expression cell line with green fluorescent protein
      and resistance genes.
AB  - In order to establish stable high expression cell lines, the eukaryotic
      expression vector pIRES2EGFP and recombinant plasmid pIRES2EGFP-TIM-3 were
      transfected into mammalian cells CHO by Lipofectamine. The transfected cells were
      cultivated under selective growth medium including G418 and green fluorescent
      protein (GFP) positive cells were sorted by FACS. Simultaneously, growing
      transfectants were selected only by G418 in the medium. The GFP expression in
      stably transfected cells was detected by FACS. Under selective growth conditions
      with G418, the percentage of GFP positive cells was reduced rapidly and GFP
      induction was low. In contrast, the percentages of GFP positive cells were
      increased gradually after FACS. By 3 rounds of GFP selection, the stable high
      expression cell lines were established. Furthermore, using FACS analysis GFP and
      the target protein TIM-3 co-expression in the stable transfectants cultured in
      nonselective medium was detected. Theses results demonstrated that the stably
      transfected cell lines that express high titer of recombinant protein can be
      simply and fleetly obtained by using GFP and selective growth medium.

PMID- 16961275
TI  - TGF-betal transgenic mouse model of thoracic irradiation: modulation of MMP-2 and
      MMP-9 in the lung tissue.
AB  - To investigate the effects of TGF-beta1 on the two gelatinases (MMP-2 and MMP-9),
      and their roles in lung remodeling after irradiation-induced lung injury.
      Expressions of TGF-beta1 were measured with western blot, and expressions of MMP
      2 and MMP-9 were analyzed with zymography in a -TGF-beta1 transgenic mouse model
      after thoracic irradiation with 12 Gy. We found expressions of TGF-beta1 in the
      lung from the transgenic mice were three folds as compared to those from control
      mice. With densitometrical analysis, we found a significant decrease in MMP-9
      activity in lung homogenates from the transgenic mice as compared with those from
      non-transgenic control mice 8 weeks after sham-irradiation (relative MMP-9
      activity: C: 1.000 0.1091; TG: 0.4772 +/- 0.470 (n = 8, P < 0.05). But MMP-2 was
      constitutively expressed in the lung homogenates from the transgenic mice as
      compared to those from control mice 8 weeks after sham-irradiation (relative MMP
      2 activity 8 weeks after sham-irradiation: C: 1.000 +/- 0.1556, TG: 1.0075 +/-
      0.1472). Eight weeks after thoracic irradiation with 12 Gy, we observed a
      significant increase of MMP-2 and MMP-9 activity in lung homogenates from both
      transgenic and normal mice. In TGF-beta1 transgenic mice relative MMP-9 activity
      was increased to 1.5321 +/- 0.2217 folds 8 weeks after thoracic irradiation with
      12 Gy as compared to those after sham-irradiation (1.000 +/- 0.2153), and
      relative MMP-2 activity was increased to 1.7142 +/- 0.4231 folds. Our results
      show that TGF-beta1 itself down-regulates activity of MMP-9, thereby decreases
      ECM degradation in lungs of TGF-beta1 transgenic mice. Also we find that ionizing
      irradiation upregulates both MMP-2 and MMP-9 activity. Over-expressions of MMP-9
      and MMP-2 after lung irradiation are involved in the inflammatory response
      associated with radiation-induced lung injury, and maybe further in radiation
      induced lung fibrosis.

PMID- 16961276
TI  - Effects of Survivin expression suppressed by short hairpin RNA on MCF-7 cells.
AB  - In order to investigate the effects of short hairpin RNA (shRNA) on the
      expression of Survivin, cell cycle and cell proliferation in MCF-7 cells, using a
      pEGFP vector which contained a U6 promoter shRNA plasmid targeted against
      survivin was constructed and transfected into MCF-7 cells. The change of the
      expression of Survivin and cell proliferation rates were detected by
      semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and MTT
      methods respectively. The change of cell cycle after transfection was analyzed by
      flow cytometry. The results indicated that the recombinant plasmid containing
      Survivin shRNA was constructed successfully, which could suppress the expression
      of Survivin at mRNA and protein level. The growth of MCF-7 cells was arrested in
      G1 phase of the cell cycle and the proliferation activity was suppressed after
      transfection. It was concluded that Survivin shRNA plasmid could knock down the
      expression of Survivin in MCF-7 cells specifically. In addition, Survivin shRNA
      plasmid could lead to G1 arrest and inhibit the proliferation of MCF-7 cells,
      which suggested that Survivin shRNA might be used as a new therapeutic method for
      breast cancer.

PMID- 16961277
TI  - Expression of cytokines IL-2, IL-10 and TNF-alpha in mice with herpes simplex
      viral encephalitis.
AB  - The expression of the cytokines IL-2, IL-10, TNF-alpha and their roles in mice
      with herpes simplex viral encephalitis (HSE) were studied. By using
      semiquantitative reverse transcription polymerase chain reaction (RT-PCR), the
      expressions of IL-2, IL-10 and TNF-alpha mRNA in control group, HSE group and
      acyclovir (ACV)-treated group were detected and the pathological changes of brain
      were observed. It was found that after HSV1 infection, the cerebral lesions of
      haemorrhage and necrosis in mice were observed under the microscopy, and the
      levels of IL-2, IL-10 and TNF-alpha were increased remarkably. After treatment
      with ACV after HSV1 infection, the cerebral lesions in mice were improved, the
      level of IL-2 maintained stable, IL-10 was increased consistently, and TNF-alpha
      was decreased significantly as compared with those in HSE group. In acute HSE,
      many cytokines are upregulated, including IL-2, IL-10 and TNF-alpha to eliminate
      virus and TH1 type response is dominant. In convalescence, there is a shift in
      the cytokine expression profile from TH1 profile to TH2 profile and the shift can
      inhibit the overexpression of immune response in animals. ACV has remarkable
      effects in the treatment of HSE.

PMID- 16961278
TI  - Difference of gene expression profiles between Barrett's esophagus and cardia
      intestinal metaplasia by gene chip.
AB  - The difference of gene expression profile changes in Barrett's esophagus (BE) and
      cardia intestinal metaplasia (CIM) epithelium was studied and the novel
      associated genes were screened in the early stage by cDNA microarray. The cDNA
      retro-transcribed from equal quantity mRNA from BE and CIM epithelial tissues
      were labeled with Cy3 and Cy5 fluorescence as probes. The mixed probe was
      hybridized with three pieces BiostarH-40s double dot human whole gene chip. The
      chips were scanned with a ScanArray 4000. The acquired images were analyzed using
      GenePix Pro 3.0 software. It was found a total of 141 genes were screened out
      that exhibited differentially expression more than 2 times in all three chips. It
      was identified that in gene expression profiles of BE, 74 genes were up-regulated
      and 67 down-regulated as compared with CIM. The comparison between the difference
      of gene expression profile changes in BE and CIM epithelia revealed that there
      existed the difference between BE and CIM at gene level. 141 genes with the
      expression more than two time were probably related to the occurrence and
      development of BE and the promotion or progress in adenocarcinoma.

PMID- 16961279
TI  - Experimental study of tissue-type plasminogen activator gene to prevent vein
      grafts stenosis.
AB  - The effects of in vivo local expression of recombined human tissue-type
      plasminogen activator (t-PA) gene on the thrombosis and neointima formation of
      vein grafts were explored. Jugular vein-to-artery bypass grafting was performed
      on 72 New Zealand white rabbits. The rabbits were divided into 3 groups according
      to the different processing methods: transfected t-PA gene group (n = 24), vector
      group (n = 24) and blank control group (n = 24). Samples of vein grafts were
      harvested at different time points after surgery. The expression of t-PA gene in
      vein graft was detected by RT-PCR and the synthesis of t-PA protein by Western
      Blot assay. The t-PA activity was measured by chromogenic substrate assay. The
      Cr51 labeled platelets accumulation in vein grafts was counted. The
      histopathological changes were compared in intima hyperplasia index among the
      three groups after operation. The results showed that at the 2nd, 5th, 14th and
      28th day after operation, RT-PCR and Western-blot confirmed the expression of t
      PA mRNA and protein at the site of gene transfer. The t-PA activity detected on
      the 2nd, 5th, 14th and 28th day in experimental group was 370.63 +/- 59.44,
      344.13 +/- 48.47, 252.87 +/- 51.80 and 161.75 +/- 68.94 U/g respectively, and
      disappeared on the 60th day and undetected in the control groups. The number of
      platelets accumulated in the vein grafts in gene group, vector group and blank
      control group was (85.04 +/- 21.58) 10(6), (225.87 +/- 85.13) 10(6) and (211.7 +/
      78.02) 10(6) respectively. The number of platelets accumulated in gene group was
      significantly fewer than that in the control groups. Morphometric analysis
      revealed that intimal hyperplasia was markedly reduced in the t-PA gene group as
      compared with that in the control groups. It was suggested that the local
      expression of t-PA gene in vein graft significantly inhibited the accumulation of
      platelets, thrombosis and concomitant intimal hyperplasia, by which stenosis of
      bypass graft could be prevented effectively.

PMID- 16961280
TI  - Smac/DIABLO promotes mitomycin C-induced apoptosis of bladder cancer T24 cells.
AB  - The enhancing effects of Smac gene on the mitomycin C-induced apoptosis of the
      bladder cancer cell line T24 were investigated. The Smac gene was transfected
      into bladder cancer cell line T24 under the induction of liposome. The intrinsic
      Smac level was detected by using immunohistochemistry and RT-PCR. The in vitro
      cellular growth activities were assayed by MTT colorimetry. Apoptosis was assayed
      by the flow cytometry. The results showed that as compared with the control
      cells, the apoptosis rate of T24 cells induced by mitomycin C was enhanced by
      transfected Smac gene. Flow cytometry revealed that, the apoptosis rate was
      18.84% and 33.52%, and 10.72% and 26.24% respectively in blank and transfected
      cells treated with 0.05 or 0.005 mg/mL mitomycin C (P < 0.05). It was concluded
      that Smac could enhance the apoptosis of T24 by mitomycin C, which could provide
      a useful experimental evidence for bladder cancer therapy.

PMID- 16961281
TI  - The use of calcaneal anatomic plate in arthroscopically-assisted open reduction
      and internal fixation of intra-articular calcaneal fractures.
AB  - To discuss and evaluate the method and effect of using calcaneal anatomic plate
      in treatment of intra-articular fractures of the calcaneus with assistant of
      arthroscope, 86 intra-articular fractures of the calcaneus in 78 patients were
      reduced by open reduction, and rigid fixation was made with calcaneal anatomic
      plate under assistant of arthroscope. The average follow-up duration was 18
      months (range 12-30 months). The effect of treatment was evaluated according to
      AOFAS and X-ray before and after operation. The results showed that 86 patients
      have obtained satisfactory reduction according to X-ray, and there was
      significant difference before and after operation (P < 0. 01), the total
      excellent and fine rate was 91.86%. Treating intra-articular fractures of the
      calcaneus with calcaneal anatomic plate under arthroscope may provide more chance
      to achieve anatomical reconstruction, which can lead to satisfied recovery of
      function and few complication.

PMID- 16961282
TI  - [Size analysis and the reference area of acetabulum-prosthesis-transplantation in
      different body positions. ].

PMID- 16961283
TI  - Construction and expression of human PTEN tumor suppressor gene recombinant
      adenovirus vector.
AB  - The recombinant defective adenovirus vector carrying human PTEN tumor suppressor
      gene was constructed by using AdEasy-1 system and its expression was detected in
      human breast cancer cell line MDA-MB-468. Human PTEN cDNA was cloned into
      adenovirus shuttle plasmid pAdTrack-CMV to generate a recombinant plasmid
      pAdTrack-CMV-PTEN, then homologeous recombination was carried out in the E. coli
      BJ5183 by contransforming linearized shuttle vector with adenovirus backbone
      plasmid pAdEasy-1. The newly recombined defective adenovirus vector Ad-PTEN
      containing green fluorescent protein (GFP) was packaged and propagated in 293
      cells. After being purified by cesium chloride gradient centrifugation, the
      adenovirus was transfected into human breast cancer cell line MDA-MB-468 in
      vitro. The expression of PTEN mRNA and protein in infected human breast cancer
      cell line MDA-MB-468 was detected by RT-PCR and Western blot respectively. The
      recombinant defective adenovirus vector carrying PTEN gene was constructed
      successfully. The viral titer of purified adenovirus was 2. 5 X 10(10) pfu/mL,
      and about 70% breast cancer cells were infected with Ad-PTEN when multiplicity of
      infection (MOI) reached 50. The exogenous PTEN mRNA and protein were expressed in
      MDA-MB-468 cells infected with Ad-PTEN by RT-PCR and Western blot. The
      recombinant defective adenovirus vector of PTEN gene was constructed successfully
      using AdEasy-1 system rapidly, which paved a sound foundation for gene study of
      breast cancer.

PMID- 16961284
TI  - Serum vascular endothelial growth factor-C and vascular endothelial growth factor
      level in patients with colorectal carcinoma and clinical significance.
AB  - Circulating vascular endothelial growth factor-C (VEGF-C) and vascular
      endothelial growth factor (VEGF) levels in patients with colorectal carcinoma
      were determined in order to assess their clinical significance as a diagnostic
      tool for monitoring lymph node metastasis. In 66 patients with colorectal
      carcinoma and 30 healthy controls, circulating VEGF-C and VEGF levels were
      assessed by using enzyme-linked immunosorbent assay (ELISA). Serum VEGF-C and
      VEGF levels were higher in patients with colorectal carcinoma than in healthy
      controls. Patients with lymph node metastasis had higher serum VEGF-C and VEGF
      levels than those without lymph node metastasis. The levels of VEGF-C and VEGF
      were higher in the invasion group than in the non-invasion group. Serum VEGF-C
      levels reached a sensitivity of 81% and a specificity of 76% with a cutoff value
      of 1438.0 pg/mL, whereas VEGF levels reached 72% sensitivity and 74% specificity
      at 240.2 pg/ mL. If 66 patients were divided into 4 groups according to the
      combined determination of VEGF-C and VEGF levels, the positive predictive value
      was 85.3%, the negative predictive value was 94.6%, and accuracy was 93.7%. It
      was suggested that circulating VEGF-C levels might provide additional information
      for distinguishing the absence from presence of lymph node metastasis in patients
      with colorectal carcinoma. The combined determination of VEGF-C and VEGF levels
      could be used as an important index for preoperatively clinical stage of
      colorectal carcinoma.

PMID- 16961285
TI  - Dynamic assessment of the focal hepatic lesion in rats using ultrasonic contrast
      agent.
AB  - The focal hepatic lesion caused by local injection of absolute alcohol in rats
      was evaluated with ultrasonic contrast agent and pathologic examination. Twenty
      adult Wistar rats weighing about 200 g were injected with absolute alcohol (0.05
      0.1 mL each one) on the exterior left lobe of the liver under the monitoring of
      ultrasound. Pulse inversion harmonic imaging was used to evaluate the focal
      lesion after bolus injection of ultrasonic contrast agent (0.05 mL/200 g) through
      caudal vein. Seven days later, the focal lesion was studied again as before. The
      exterior left lobe of liver with focal lesion was incised and underwent
      pathologic examination. The results showed that all of the focal lesions could be
      defined clearly after bolus injection of the ultrasonic contrast agent under the
      mode of pulse inversion harmonic imaging. There was good correlation between the
      size of the focal lesion measured by ultrasound on the 7th day after the
      "ablation" under the mode of pulse inversion harmonic imaging and that gotten by
      pathologic examination (P = 0.39). The focus size measured by ultrasound right
      after the ablation was larger than that gotten by pathologic examination (P =
      0.002). It was concluded that ultrasonic contrast agent plus pulse inversion
      harmonic imaging could be used to assess the size of the focal hepatic lesion
      caused by local injection of absolute alcohol in rats.

PMID- 16961286
TI  - Assessment of regional myocardial function in patients with hypertrophic
      cardiomyopathy by tissue strain imaging.
AB  - The value of tissue strain imaging (SI) in regional myocardial systolic and
      diastolic function assessment was studied. In 18 patients with nonobstructive
      hypertrophic cardiomyopathy (HCM) and 20 age-matched healthy subjects, regional
      myocardial longitudinal peak systolic strain in eject time (represented by
      epsilon(et)) was measured at basal, mid and apical segments of septal, lateral
      and posterior walls of the left ventricle (LV) and compared between groups.
      Epsilon(et) had no significant difference between segments in control group (P >
      0.05), which displayed a decreasing trend from basal segments to apical ones.
      Epsilon(et) in the HCM group was significantly decreased (P < 0.05) as compared
      with that in the healthy group. In the HCM group, epsilon(et) in the midseptum
      was significantly less than at the basal and apical septum, and was also less
      than at the rest LV walls in the same group (P < 0.01). The systolic reversed
      epsilon(et) was noticed in 35% of the hypertrophic segments in HCM group.
      Significantly negative correlation existed between the absolute value of
      epsilon(et) and wall thickness in the midseptum (r = -0.83). The post-systolic
      strain (PSS) segment number the and amplitudes in healthy group were
      significantly less than those in HCM group (P < 0.05). Both regional myocardial
      systolic and diastolic functions were impaired in hypertrophic or non
      hypertrophic segments in patients with the HCM, especially in hypertrophic
      segments. Strain imaging technique is a sensitive and accura tool in myocardial
      dysfunction assessment.

PMID- 16961287
TI  - Noninvasive detection of coronary artery stenosis using 16-slice spiral CT: a
      comparison with selective X-ray coronary angiography.
AB  - The role of 16-slice spiral CT was evaluated in the diagnosis of coronary
      stenosis, with selective X-ray coronary angiography (SCA) serving as the
      reference standard. Sixty-five patients who were suspected of having coronary
      heart disease, without percutaneous transluminal coronary angioplasty or coronary
      bypass-grafting, were investigated using 16-slice CT. Eight patients with pre
      scan heart rate of more than 80 beats/min were given beta-blockers. After the
      retrospectively ECG-gated axial imaging reconstruction, volume redering (VR),
      multi-planar reconstruction (MPR), curved MPR and maximum intensity projection
      (MIP) were used to reconstruct. Every segment of coronary artery with a diameter
      > or = 1.5 mm was assessed, and the presence on CT with a stenosis exceeding 50%
      diameter reduction was compared with that on SCA. The reasons which lead to some
      segments unevaluable were analysed. Compared with SCA, 93% coronary segments and
      94% main branches were evaluable. Residual cardiac motion artifacts, severe
      calcification and poor opacification made 58%, 28% and 14% of the remaining 60
      segments unevaluable respectively. Without routine administration of beta
      blockers, good coronary imaging quality can be acquired using 16-slice spiral CT.
      It is a reliable noninvasive method for detection of obstructive coronary artery
      disease.

PMID- 16961288
TI  - Experimental study of multi-slice spiral CT perfusion imaging in VX2 soft-tissue
      tumor of rabbits.
AB  - An experimental animal model of malignant soft-tissue tumor was established to
      investigate the applied value of multi-slice spiral CT perfusion imaging
      preliminarily. Ten New Zealand white rabbits which were implanted with VX2 tumor
      in either proximal thigh were subjected to CT plain scan and perfusion scan two
      weeks later respectively, then the original perfusion images were transmitted to
      AW4.0 Workstation. The functional maps and perfusion parameters including blood
      flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface
      (PS) were computed and analyzed. All the values of BF, BV and PS in VX2 soft
      tissue tumors were obviously higher while the MTT-values were lower than those in
      the normal muscular tissues significantly. It was suggested that multi-slice
      spiral CT perfusion imaging is an accurate, convenient and relatively safe
      functional imaging technique, and can give a quantitative assessment to
      angiogenesis and blood perfusion of soft-tissue tumors.

PMID- 16961290
TI  - Relationship between single nucleotide polymorphism in TNF-alpha gene promoter
      region and inhibitory effects of triptolide on TNF-alpha production in peripheral
      blood mononuclear cells of healthy humans.
AB  - The relationship between tumour necrosis factor-alpha (TNF-alpha) gene
      polymorphism and inhibitory effects of triptolide on TNF-alpha production from
      peripheral blood mononuclear cells (PBMC) of healthy humans was investigated.
      Genomic DNA from 41 healthy people was typed for TNF-alpha--308 polymorphism by
      allele-specific polymorphism chain reaction (AS-PCR). The TNF-alpha concentration
      in the supernatant was measured by ELISA. The results showed that the production
      of TNF-alpha from TNF-alpha--308 non-G/G genotype PBMC was higher than that from
      TNF-alpha--308 G/G genotype PBMC after stimulated by LPS. Triptolide could lower
      the production of TNF-alpha from G/ G genotype PBMC, but had no effect on the
      level of TNF-alpha from non-G/G genotype PBMC. It was concluded that TNF-alpha
      gene polymorphism was related to the TNF-alpha production from triptolide
      inhibited PBMC culture in healthy humans.

PMID- 16961289
TI  - Effect of triptolide on expression of receptor activator of nuclear factor-kappaB
      ligand in rat adjuvant induced arthritis.
AB  - The effect of triptolide (TP) on the expression of receptor activator of nuclear
      factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) was explored in rat
      adjuvant induced arthritis (AA). AA was induced in Wistar rats. Arthritis rats
      were treated with TP and methotrexate (MTX) at the onset (day 9) of arthritis. On
      the peak of arthritis (day 24), the expression of RANKL and OPG protein in the
      joints and RANKL mRNA in peripheral blood mononuclear cells (PBMC) was detected.
      TNF-alpha and IL-1beta levels in peripheral blood were determined. Bone erosion
      scores were also evaluated. The results showed that bone erosion scores in TP and
      MTX groups were lower than in AA group (P < 0.01); The expression levels of RANKL
      in the synovium (P < 0.01) and bone (P < 0.05), and OPG level in synovium (P <
      0.05) were lower in TP group than in AA group (P < 0.05). In TP group, the
      expression levels of RANKL mRNA and TNF-alpha, IL-1beta in PBMC were lower than
      in AA group (all P < 0.01). It was concluded that TP could inhibit rat adjuvant
      arthritis bone erosion by suppressing the expression of RANKL.

PMID- 16961291
TI  - Ursodeoxycholic acid in the treatment of intraheptic cholestasis of pregnancy.
AB  - In order to observe the effect of ursodeoxycholic acid (UDCA) in the treatment of
      intrahepatic cholestasis of pregnancy (ICP), 68 patients with ICP were equally
      divided into treatment group and control group at random. The patients in
      treatment group were administered with UDCA 300 mg three times every day and
      those in control group received a combination of 10% glucose, Vitamin C and
      Inosine. Itching scores, serum ALT and total bile acids (TBA) were measured
      before, during and after treatment. The results showed that as compared with
      those before treatment, itching scores, serum ALT and TBA were significantly
      reduced after treatment (P < 0.05). The occurrences of premature labor, fetal
      asphyxia and meconium staining in amniotic fluid were significantly lower in
      treatment group than in control group (P < 0.05). It was suggested that UDCA was
      an effective drug in the treatment of ICP.

PMID- 16961292
TI  - Experimental study on meiotic spindles and chromosomes of mouse mature (M II)
      stage oocytes under laser scanning confocal microscopy.
AB  - Taking the mouse as a model, the experimental method of observing the morphology
      of meiotic spindles and chromosomes in mature oocytes were investigated in order
      to evaluate the effects of various interventions on the quality of oocytes
      accurately and rapidly. Laser scanning confocal microscope (LSCM) was used to
      examine the meiotic spindles and chromosomes by the technologies of optical
      section and three-dimensional (3D) image reconstruction. The results showed that
      the configurations of meiotic spindles and chromosomes could be observed clearly
      by LSCM. The normal rate of meiotic spindles and chromosomes was 82% and 86%
      respectively. It was concluded that the LSCM was a valid instrument to observe
      the meiotic spindles and chromosomes of mature oocytes and could be used as a
      valid method to evaluate the quality of M II oocytes.

PMID- 16961293
TI  - Expression of endothelial nitric oxide synthase traffic inducer in the placenta
      of pregnancy induced hypertension.
AB  - The expression of endothelial nitric oxide synthase traffic inducer (NOSTRIN) in
      the placenta of the patients with pregnancy induced hypertension (PIH) was
      detected and its role in the pathogenesis of PIH was studied. The pathological
      changes in placental vessels were observed by HE staining. NO2-/NO3-, the stable
      metabolic end products of NO, was measured with nitrate reductase. The eNOS
      activity in placental tissues was assayed by spectrophotometry. Western blot
      analysis was applied to detect NOSTRIN expression. The incidence of thickening
      and fibronoid necrosis of placental vessels was significantly higher in women
      with PIH than in the normal group (P < 0.01). The levels of placental NO2-/NO3-
      in PIH patients (27.53 +/- 7.48 micromol/mg) were significantly lower than in
      normal group (54.27 +/- 9.53 micromol/mg, P < 0.01). The activity of eNOS was
      significantly decreased in PIH group (12.826 +/- 3.61 U/mg) as compared with that
      in normal group (21.72 +/- 3.83 U/mg, P < 0.01). Western blot analysis revealed
      that both groups expressed 58 kD NOSTRIN, but the protein level was significantly
      higher in women with PIH than in the normal group (P < 0.01). A significant
      negative correlation existed between the expression of NOSTRIN protein and the
      activity of eNOS in placental tissue of women with PIH (r = -0.57, P < 0.01). It
      was concluded that the level of NOSTRIN expression in placenta of women with PIH
      was increased, which may play an important role in the pathogenesis of PIH.

PMID- 16961294
TI  - Expression of MTA2 gene in ovarian epithelial cancer and its clinical
      implication.
AB  - In order to investigate the roles of MTA2 in the pathogenesis of ovarian
      epithelial cancer, the expression of MTA2 in 4 ovarian cell lines were detected
      by semi-quantitative RT-PCR and Western-blot assays. MTA2 expression in normal,
      borderline, benign and malignant epithelial ovarian tissues was
      immunohistochemically examined. The expression of MTA2 mRNA and protein was
      detected in all of 4 cell lines of ovarian epithelial cancer. The expression of
      MTA2 mRNA and protein was higher in strong migration cell lines than in weak
      migration ones. In borderline and malignant ovarian tissues tested, MTA2 staining
      was dramatically stronger than in normal and benign tissues (P < 0.01). The
      expression levels in malignant ovarian tissues were significantly higher than
      that in borderline epithelial ovarian tissues (P < 0.01). The expression of MTA2
      was correlated with clinical stage, histopathological grade and lymph node
      metastasis. It was concluded that the high expression of MTA2 was associated with
      more aggressive behaviors of epithelial ovarian cancer. MTA2 provides a novel
      indicator of ovarian cancer.

PMID- 16961295
TI  - Modulation of matrix metalloproteinase and TIMP-1 expression by TGF-beta1 in
      cultured human RPE cells.
AB  - In order to investigate the effects of TGF-beta1 on the expression of MMP-2, -9
      and TIMP-1 in human retinal pigment epithelial (RPE) cells, the third-sixth
      passage cultured RPE cells were treated with TGF-beta1 at different
      concentrations (0.01, 0.1, 1.0, 10 ng/mL), the expression of MMP-2, -9 and TIMP-1
      mRNA was detected by semi-quantitative RT-PCR assays. MMP-2, -9 and TIMP-1 mRNA
      were expressed in the cultured RPE cells. The values of MMP-2/beta-actin in the
      cells treated with 0.1, 1.0, 10 ng/mL TGF-beta1 were 1.04 +/- 0.04, 1.07 +/- 0.02
      and 1.11 +/- 0.03, respectively, significantly higher than in the control group
      (0.96 +/- 0.03, P < 0.05-0.01). The expression of MMP-2 mRNA could be up
      regulated by TGF-beta1, in a dose-dependent manner. The expression of MMP-9 mRNA
      in the cultured RPE cells was slightly up-regulated by various TGF-beta1
      concentrations treatment. The values of TIMP-1/beta-actin in the cells treated
      with 0.01 and 0.1 ng/ mL TGF-beta1 were 0.85 +/- 0.01 and 0.97 +/- 0.02
      respectively, significantly lower than in the control group (1.07 +/- 0.04, P <
      0.01), indicating that the expression of TIMP-1 mRNA was down-regulated by TGF
      beta1 at low concentrations. But along with the increase of TGF-beta1
      concentrations (1.0 and 10 ng/mL), the expression of TIMP-1 mRNA was slightly up
      regulated, not significantly different from that in the control group (P > 0.05).
      It was concluded that TGF-beta1 might play an important role in the up-regulation
      of the expression of MMP-2 in RPE cells and result in a directional shift in the
      balance between MMP and TIMP. This may be facilitated for RPE cells to migrate in
      the pathogenesis of vitreoretinopathy.

PMID- 16961296
TI  - Effects of CTLA4-Ig gene-modified dendritic cells on the corneal allografts.
AB  - In order to investigate the effects of mouse CTLA4Ig gene-modified dendritic
      cells (DCs) on the survival of the corneal allografts in rats, the plasmid
      PG?CTLA4Ig was transfected into DCs of F344 rats mediated by Lipofectamine 2000.
      The expression of CTLA4Ig was detected by immunofluorescent microscopy. The
      effects of donor DCs on the proliferation of T cells in Lewis rats (recipients)
      were tested by by CCK8. Corneal transplantation was performed from F344 rats to
      Lewis rats. The DCs modified with CTLA4Ig gene were injected into the Lewis rats
      on the day 0 and 3 after transplantation. The movement of the DCs after
      modification in vivo was observed by immunofluorescent microscopy, and the
      survival of corneal allografts was evaluated by Holland criterion. The results
      showed that the CTLA4Ig-modified DCs could restrain the proliferation of
      allogenetic T cells. The CTLA4Ig-modified DCs prolonged survival of corneal
      allografts. (P < 0.01). It was suggested that the injection of CTLA4Ig gene
      modified DCs could obviously inhabit the allograft rejection and prolong the
      survival of corneal allografts.

PMID- 16961297
TI  - Inhibitory effect of dexamethasone on TGF-beta1 expression of rabbit ciliary
      pigment epithelia cultured in vitro.
AB  - In order to elucidate the effect of dexamethasone on the expression of
      transforming growth factor-beta1 (TGF-beta1) in ciliary pigment epithelial (CPE)
      cells cultured in vitro, rabbit CPE cells were cultured in vitro, treated with
      DMEM medium containing 0, 1 x 10(-8), 5 x 10(-8), 10 x 10(-8) and 50 x 10(-8)
      mol/L dexamethasone respectively for 5 days. The TGF-beta1 expression was
      detected by immunohistochemistry Supervision methods and analyzed semi
      quantitatively by HMIAS-2000 image system. As opposed to in vivo, rabbit CPE
      cells expressed TGF-beta1 under cultured circumstance in vitro. The gray scales
      of the positive yellow staining in the groups of 1 x 10(-8), 5 x 10(-8), 10 x 10(
      8) and 50 x 10(-8) mol/L dexamethasone were 136.57 +/- 4.43, 140.20 +/- 6.10,
      142.98 +/- 2.99, 146.80 +/- 1.68 and 150.05 +/- 1.94 respectively. When the
      concentrations of dexamethasone were equal to or higher than 5 x 10(-8) mol/L
      and, the expression of TGF-beta1 was inhibited. 10(-7) mol/L dexamethasone showed
      a significant inhibition. It was suggested that CPE cells possess the potential
      ability of synthesizing and expressing TGF-beta1. The inhibition of TGF-beta1
      expression by dexamethasone may be beneficial to the treatment of proliferative
      vitroretinopathy, also exert some influence on the secretion of aqueous humor and
      ciliary inflammation.

PMID- 16961298
TI  - Measurement of intraocular pressure after LASIK by dynamic contour tonometry.
AB  - Changes of corneal properties induced by laser in situ keratomileusis (LASIK)
      results in low inaccurate intraocular pressure (IOP) readings by Goldmann
      applanation tonometry (GAT). Before and after LASIK, the applied value of IOP,
      measured by dynamic contour tonometry (DCT) in comparison to GAT, was evaluated.
      Before and 1, 4 weeks after LASIK, the IOP in 30 cases (60 eyes) was measured by
      GAT and DCT respectively. The obtained results were statistically processed by
      SPSS11.5 statistical software. The results showed that central corneal thickness
      (CCT) could affect GAT measurements but not DCT measurements. The comparison of
      IOP one and 4 weeks after LASIK revealed that the readings from GAT was
      separately decreased by 5.00 +/- 1.12 and 5.45 +/- 1.13 mmHg as compared with
      those before LASIK, while those from DCT had no significant difference. It was
      concluded that LASIK-induced changes of CCT could influence the accuracy of GAT
      measurements, but had no influence on those from DCT. DCT was more beneficial to
      the measurements of IOP in normal eyes and those subject to LASIK surgery.

PMID- 16961299
TI  - Localization of NKCC1 in the cochlea and morphology of the cochlea in NKCC1
      knockout mice.
AB  - The distribution of the Na-K-2Cl co-transporter (NKCC1) in the cochlear K+
      cycling pathway in cochlea and cochlear histological changes in the NKCC1
      knockout mice were investigated. By using immunohistochemistry and toluidine blue
      staining, the localization of NKCC1 in cochlea of the C57BL/6J mice and the
      cochlear histological changes in the NKCC1 knockout mice were observed. It was
      found that the NKCC1 was expressed mainly in the stria marginal cells and the
      fibrocytes in the inferior portion of the spiral ligament in the adult C57BL/6J
      mice. Subpopulation of the fibrocytes in the suprastrial region and the limbus
      was also moderately immunoreactive. While in the cochlea of the NKCC1 knockout
      mice, Reissner's membrane was collapsed and scala media disappeared, accompanied
      with the loss of inner hair cells, outer hair cells and the support cells. The
      tunnel of Corti was often absent. All the findings suggested the localization of
      NKCC1 in the cochlea was closely correlated with cochlear K+ cycling. Loss of
      NKCC1 led to the destruction of the cochlear structures, and subsequently
      influenced the physiological function of cochlea.

PMID- 16961300
TI  - Expression of CD40 and CD40L on peripheral blood mononuclear cells in patients
      with condyloma acuminatum.
AB  - To observe the expression of CD40/CD40L on peripheral blood mononuclear cells
      (PBMC) in patients with condyloma acuminatum (CA), flow cytometry was employed to
      examine the expression of CD40 and CD40L on PMBC in 36 patients with CA and 20
      healthy controls. Our results showed that mean level of CD40 expression in CA
      patients was significantly lower than that in the controls (6.58% +/- 2.74% vs
      14.81% +/- 6.12%, t = 5.703, P < 0.05); the average level of CD40L in CA patients
      was also significantly lower than that in the controls (0.73% +/- 0.54% vs 2.67%
      +/- 2.43%, t = 3.532, P < 0.05). Our results suggest that the reduced
      costimulatory interaction of CD40 and CD40L in CA patients may be one of the
      important factors responsible for the low cellular immunity.

PMID- 16961301
TI  - Relationship between family characteristics and aggressive behaviors of children
      and adolescents.
AB  - In order to identify family factors obviously relevant to aggression, and offer a
      theoretical foundation for the prevention of aggression, 4010 students from
      primary and secondary schools in 5 different areas in Hubei province were
      surveyed. The Child Behavior Checklist " parents' form" (Chinese version) and the
      four scales of Family Environment Scale were used. A multiple logistic regression
      was used to identify risk factors of children's and adolescents' aggressive
      behavior. The results showed that maternal education, paternal occupation, family
      type, parental child-rearing attitude and patterns, students' interpersonal
      relationship were significantly associated with the children's and adolescents'
      aggression. The risk factors of aggression were parental child-rearing patterns,
      peer relationship, teacher-student relationship, and family conflicts.

PMID- 16961302
TI  - Diagnosis of infectious mononucleosis by combined detection of atypical
      lymphocytes and transaminase.
AB  - In order to explore the value of combined detection of atypical lymphocytes (ATL)
      and transaminase (alanine aminotransferase, ALT; asparate aminotransferase, AST)
      in the diagnosis of infectious mononucleosis (IM), The data of blood routine and
      liver function were collected from 54 IM patients, 34 acute hepatitis (AH)
      patients, 44 upper respiratory infection (URI) patients in Union Hospital during
      March 2002 to March 2005. Same data were also collected from 40 healthy children
      as normal control. These data were analyzed retrospectively. Both proportion of
      atypical lymphocytes and enzyme activity of transaminase were elevated
      simultaneously (ALT > 40 IU/L, AST > 45 IU/L) in 57.4% (31/54) IM patients. There
      was significant difference (P < 0.01) between IM group and the other groups.
      Combined detection of atypical lymphocytes and transaminase can be regarded as a
      diagnostic marker of infectious mononucleosis.

PMID- 16961303
TI  - Analysis on antimicrobial resistance of clinical bacteria isolated from county
      hospitals and a teaching hospital.
AB  - The distinction of antimicrobial resistance of clinical bacteria isolated from
      county hospitals and a teaching hospital was investigated. Disc diffusion test
      was used to study the antimicrobial resistance of isolates collected from county
      hospitals and a teaching hospital. The data was analyzed by WHONET5 and SPSS
      statistic software. A total of 655 strains and 1682 strains were collected from
      county hospitals and a teaching hospital, respectively, in the year of 2003. The
      top ten pathogens were Coagulase negative staphylococci (CNS), E. coli,
      Klebsiella spp., S. areus, P. aeruginosa, Enterococcus spp., Enterobacter spp.,
      otherwise Salmonella spp., Proteus spp., Shigella spp. in county hospitals and
      Streptococcus spp., Acinetobacter spp., X. maltophilia in the teaching hospital.
      The prevalence of multi-drug resistant bacteria was 5% (4/86) of methicillin
      resistant S. areus (MRSA), 12% (16/133) and 15.8% (9/57) of extended-spectrum
      beta-lactamases producing strains of E. coli and Klebsiella spp., respectively,
      in county hospitals. All of the three rates were lower than that in the teaching
      hospital and the difference was statistically significant (P < 0. 01). However,
      the incidence of methicillin-resistant CNS (MRCNS) reached to 70% (109/156) in
      the two classes of hospitals. Generally, the antimicrobial resistant rates in the
      county hospitals were lower than those in the teaching hospital, except the
      resistant rates of ciprofloxacin, erythromycin, clindamycin, SMZco which were
      similar in the two classes of hospitals. There were differences between county
      hospitals and the teaching hospital in the distribution of clinical isolates and
      prevalence of antimicrobial resistance. It was the basis of rational use of
      antimicrobial agents to monitor antimicrobial resistance by each hospital.

PMID- 16961304
TI  - Topology characterization by MALDI-ToF-MS of enzymatically synthesized
      poly(lactide-co-glycolide).
AB  - Lipase catalyzed copolymerization of the monomers lactide and glycolide by
      Pseudomonas cepacia employing a molar ratio of 80L/20G has been studied. The
      copolymers were characterized by MALDI-ToF-MS, DSC, SEC and NMR. MALDI-ToF-MS has
      successfully been used not only to determine end groups and chemical composition
      but even the microstructure of the copolymers. We demonstrated that for this
      lipase catalyzed copolymerization, the main product of the reaction at 100
      degrees C was linear homopolymer of lactide while at 130 degrees C the main
      product was cyclic random copolymer.

PMID- 16961305
TI  - Synthesis of highly water-soluble fluorescent conjugated glycopoly(p-phenylene)s
      for lectin and Escherichia coli.
AB  - Two facile, convenient, and versatile synthetic approaches are used to covalently
      attach carbohydrate residues to conjugated poly(p-phenylene)s (PPPs) for highly
      water-soluble PPPs bearing alpha-mannopyranosyl and beta-glucopyranosyl pendants
      (polymers A and B), which highly fluoresce in phosphate buffer (pH 7.0). The post
      polymerization functionalization approach is to treat bromo-bearing PPP (polymer
      1) with 1-thiolethyl-alpha-D-mannose tetraacetate or 1-thiol-beta-D-glucose
      tetraacetate in THF solution in the presence of K(2)CO(3) at room temperature
      through formation of thioether bridges, affording polymer 2a or 2b. The
      prepolymerization functionalization approach is to polymerize a well-defined
      sugar-carrying monomer, affording polymer 2a. Polymers 2a and 2b were
      deacetylated under Zemplen conditions in methanol and methylene chloride
      containing sodium methoxide, affording polymers A and B, respectively. The
      multivalent display of carbohydrates on the fluorescent conjugated glycopolymer
      overcomes the characteristic low binding affinity of the individual carbohydrates
      to their receptor proteins. Titration of concanavalin A (Con A) to alpha-mannose
      bearing polymer A resulted in significant fluorescent quenching of the polymer
      with Stern-Volmer quenching constant of 4.5 x 10(7). Incubation of polymer A with
      Escherichia coli (E. coli) lead to formation of fluorescently stained bacterial
      clusters. Beta-glucose-bearing polymer B displayed no response to Con A and E.
      coli.

PMID- 16961306
TI  - Simultaneous phase transition of ELP tagged molecules and free ELP: an efficient
      and reversible capture system.
AB  - In this paper, we demonstrate proof-of-principle for a method that allows
      selective recovery of molecules present at very low concentrations in complex
      mixtures. The method makes use of an elastin-like polypeptide (ELP) as a
      coaggregant for the capture of an ELP tagged recombinant protein present at
      concentrations as low as 10 pM, with a recovery higher than 90%. This
      coaggregation process was found to be independent of the concentration, at least
      up to 10 pM concentration of the ELP tagged protein. The coaggregation process is
      highly specific as was demonstrated by spiking crude cell lysate with the ELP
      tagged recombinant protein to a final concentration of 1 nM and recovering more
      than 80% of it to a high level of purity. The method should be particularly
      useful for high-throughput proteomic studies, where small amounts of poorly
      expressed proteins could be recovered for analysis by mass spectrometry. In a
      more general context, the concept presented in this paper provides a method that
      is highly efficient, specific, and fully reversible, which should render it
      useful in areas other than recombinant protein purification.

PMID- 16961307
TI  - Chemical reaction at specific sites and reaction-induced self-assembly as
      observed by in situ and real time SANS: enzymatic polymerization to synthetic
      cellulose.
AB  - We have investigated the self-assembling process of cellulose artificially
      synthesized via enzymatic polymerization by means of in situ and time-resolved
      SANS (small-angle neutron scattering). The results elucidated the following: (i)
      Cellulose molecules synthesized at a special reaction site of the enzyme
      (cellulase) located on or near the smooth surface of self-assembled enzymes
      formed in the reaction medium. (ii) The synthesized molecules associated
      themselves via DLA (diffusion-limited association) and crystallized into fibrils.
      (iii) The fibrils formed the aggregates, which had surface fractal dimension D(s)
      increasing from 2 to 2.3 with the reaction time, on the smooth surface of the
      enzyme aggregates.

PMID- 16961308
TI  - Release of plasmid DNA from intravascular stents coated with ultrathin
      multilayered polyelectrolyte films.
AB  - Materials that permit control over the release of DNA from the surfaces of
      topologically complex implantable devices, such as intravascular stents, could
      contribute to the development of new approaches to the localized delivery of DNA.
      We report the fabrication of ultrathin, multilayered polyelectrolyte films that
      permit both the immobilization and controlled release of plasmid DNA from the
      surfaces of stainless steel intravascular stents. Our approach makes use of an
      aqueous-based, layer-by-layer method for the assembly of nanostructured thin
      films consisting of alternating layers of plasmid DNA and a hydrolytically
      degradable polyamine. Characterization of coated stents using scanning electron
      microscopy (SEM) demonstrated that stents were coated uniformly with an ultrathin
      film ca. 120 nm thick that adhered conformally to the surfaces of stent struts.
      These ultrathin films did not crack, peel, or delaminate substantially from the
      surface after exposure to a range of mechanical challenges representative of
      those encountered during stent deployment (e.g., balloon expansion). Stents
      coated with eight bilayers of degradable polyamine and a plasmid encoding
      enhanced green fluorescent protein (EGFP) sustained the release of DNA into
      solution for up to four days when incubated in phosphate buffered saline at 37
      degrees C, and coated stents were capable of mediating the expression of EGFP in
      a mammalian cell line without the aid of additional transfection agents. The
      approach reported here could, with further development, contribute to the
      development of localized gene-based approaches to the treatment of cardiovascular
      diseases or related conditions.

PMID- 16961309
TI  - Micellization phenomena of amphiphilic block copolymers based on methoxy
      poly(ethylene glycol) and either crystalline or amorphous poly(caprolactone-b
      lactide).
AB  - This study focuses on the aggregation behavior of the biodegradable amphiphilic
      block copolymers based on methoxy poly(ethylene glycol) (mPEG) as a hydrophilic
      block and either crystalline poly(caprolactone-b-l-lactide) (P(CL-LLA)) or
      amorphous poly(caprolactone-b-D,L-lactide) (P(CL-DLLA)) as a hydrophobic block.
      These block copolymers have a strong tendency to form micelles in aqueous medium,
      with very low critical micelle concentrations (CMCs). The CMC of P(CL-LLA)-b-mPEG
      is higher than that of P(CL-DLLA)-b-mPEG when the mPEG block has the same
      molecular weight. Furthermore, the partition equilibrium coefficient (K(v)) of
      pyrene in the micellar solution of P(CL-LLA)-b-mPEG copolymer was lower than that
      of P(CL-DLLA)-b-mPEG copolymer when the mPEG block was the same length. These
      differences were believed to be related to the physical state of the core-forming
      blocks, i.e., the crystalline P(CL-LLA) block and the amorphous P(CL-DLLA) block.
      The TEM images showed that micelles formed by P(CL-LLA)-b-mPEG assembled in a
      cylindrical morphology, whereas those formed by P(CL-DLLA)-b-mPEG took a
      classical spherical shape. In addition, with differential scanning calorimetry
      (DSC) and wide-angle X-ray diffraction (WAXD) analyses, it is believed that the
      crystallization tendency of the core-forming blocks is the main factor governing
      the morphology of micelles in water. A possible mechanism for the cylindrical
      assembly morphology was discussed.

PMID- 16961310
TI  - Synthesis, characterization, and pH-triggered dethreading of alpha-cyclodextrin
      poly(ethylene glycol) polyrotaxanes bearing cleavable endcaps.
AB  - The synthesis, characterization, and degradation kinetics of three alpha
      cyclodextrin (alpha-CD)-poly(ethylene glycol) (PEG) polyrotaxanes with endcaps
      that were installed using Cu(I)-catalyzed Huisgen cyclization is reported.
      PEG1500, azidated with azidoacetic acid, was threaded with alpha-CD to form a
      pseudopolyrotaxane that was then capped in up to 82% yield with three different
      substituents to provide polyrotaxanes that were either acid-, base-, or fluoride
      sensitive. NMR, GPC, XRD, and AFM methods were used to characterize the
      polyrotaxanes. Dethreading rates upon exposure to mild deprotection conditions
      were monitored by turbidity analysis. The vinyl ether-endcapped polyrotaxane is
      stable at pH 7 for 16 h but is solubilized at approximately 0.0211 min(-1) at pH
      4. The ester-endcapped polyrotaxane is solubilized at 0.0122 min(-1) at pH 12.1.
      Our results show that pH-triggerable polyrotaxanes can be readily and efficiently
      prepared from pseudopolyrotaxanes in high yield by Huisgen cyclization of azido-
      and alkynyl-modified precursors in the presence of Cu(I).

PMID- 16961311
TI  - Biological impact of polyacetal particles on loosening of isoelastic stems.
AB  - The aim of our study was to identify biological factors responsible for premature
      loosening of polyacetal hip stems. The results of histological analyses of the
      tissue around 11 total hip prostheses with loosened polyacetal femoral stems were
      compared to those obtained in a group of 11 total hip prostheses with loosened
      metal (CoCr) femoral components. A higher number of polymer wear particles
      surrounded by giant cells, more bone chips, and a more extensive necrosis were
      found around loosened polyacetal stems. Histomorphological characteristics of
      polyacetal wear particles containing BaSO(4) granules in the tissue around
      loosened polyacetal stems were described. Radiological evaluation of the wear of
      polyethylene cups suggested that elastic modulus of the stem had no influence on
      the wear of polyethylene cups. This study indicates that polyacetal wear
      particles have a great biological potential accelerating the process of
      loosening.

PMID- 16961312
TI  - Characterization by Raman microspectroscopy of the strain-induced conformational
      transition in fibroin fibers from the silkworm Samia cynthia ricini.
AB  - Raman microspectroscopy has been used to quantitatively study the effect of a
      mechanical deformation on the conformation and orientation of Samia cynthia
      ricini (S. c. ricini) silk fibroin. Samples were obtained from the aqueous
      solution stored in the silk gland and stretched at draw ratios (lambda) ranging
      from 0 to 11. Using an appropriate band decomposition procedure, polarized and
      orientation-insensitive spectra have been analyzed to determine order parameters
      and the content of secondary structures, respectively. The data unambiguously
      show that, in response to mechanical deformation, S. c. ricini fibroin undergoes
      a cooperative alpha-helix to beta-sheet conformational transition above a
      critical draw ratio of 4. The alpha-helix content decreases from 33 to 13% when
      lambda increases from 0 to 11, while the amount of beta-sheets increases from 15
      to 37%. In comparison, cocoon silk is devoid of alpha-helical structure and
      always contains a larger amount of beta-sheets. Although the presence of
      isosbestic points in different spectral regions reveals that the conformational
      change induced by mechanical deformation is a two-state process, our results
      suggest that part of the glycine residues might be incorporated into beta
      poly(alanine) structures. The beta-sheets are initially isotropically distributed
      and orient along the fiber axis as lambda increases, but do not reach the high
      level of orientation found in the cocoon fiber. The increase in the orientation
      level of the beta-sheets is found to be concomitant with the alpha --> beta
      conformational conversion, whereas alpha-helices do not orient under the applied
      strain but are rather readily converted into beta-sheets. The components assigned
      to turns exhibit a small orientation perpendicular to the fiber axis in stretched
      samples, showing that, overall, the polypeptide chains are aligned along the
      stretching direction. Our results suggest that, in nature, factors other than
      stretching contribute to the optimization of the amount of beta-sheets and the
      high degree of orientation found in natural cocoon silk.

PMID- 16961313
TI  - Morphological and optical characterization of polyelectrolyte multilayers
      incorporating nanocrystalline cellulose.
AB  - Aqueous layer-by-layer (LbL) processing was used to create polyelectrolyte
      multilayer (PEM) nanocomposites containing cellulose nanocrystals and
      poly(allylamine hydrochloride). Solution-dipping and spin-coating assembly
      methods gave smooth, stable, thin films. Morphology was studied by atomic force
      microscopy (AFM) and scanning electron microscopy (SEM), and film growth was
      characterized by X-ray photoelectron spectroscopy (XPS), ellipsometry, and
      optical reflectometry. Relatively few deposition cycles were needed to give full
      surface coverage, with film thicknesses ranging from 10 to 500 nm. Films prepared
      by spin-coating were substantially thicker than solution-dipped films and
      displayed radial orientation of the rod-shaped cellulose nanocrystals. The
      relationship between film color and thickness is discussed according to the
      principles of thin film interference and indicates that the iridescent properties
      of the films can be easily tailored in this system.

PMID- 16961314
TI  - Porous scaffolds from high molecular weight polyesters synthesized via enzyme
      catalyzed ring-opening polymerization.
AB  - Several aliphatic polyesters have been synthesized until now using enzyme
      catalyzed ring-opening polymerization (ROP) of different lactones, although their
      molecular weight, hence mechanical strength, was not sufficient enough to
      fabricate porous scaffolds from them. To achieve this target, 1,5-dioxepan-2-one
      (DXO) and epsilon-caprolactone (CL) were polymerized in bulk with Lipase CA as
      catalyst at 60 degrees C, and porous scaffolds were prepared from the polymers
      obtained thereof using a salt leaching technique. The CL/DXO molar feed ratio was
      varied from 1.5 to 10, and the reactivity ratios of CL and DXO were determined
      using the Kelen-Tudos method under such conditions of polymerization. NMR results
      showed a slightly lower CL/DXO molar ratio in the copolymers than in the feed due
      to high reactivity of DXO toward Lipase CA catalysis. The crystallinity of the
      PCL segment of the copolymers was affected by the presence of soft and amorphous
      DXO domains. The copolymers having high CL content were thermally more stable.
      The porosity of the scaffolds was in the range 82-88%, and the SEM analysis
      showed interconnected pores in the scaffolds. Of the two parameters which could
      affect the mechanical properties, viz., the copolymer composition and the
      scaffold pore size, the pore size showed a significant effect on the mechanical
      properties of the scaffolds. The porous scaffolds developed in this way for
      tissue engineering are free from toxic organometallic catalyst residues, and they
      are highly suitable for biomedical applications.

PMID- 16961315
TI  - Fabrication of protein nanotubes based on layer-by-layer assembly.
AB  - Nanotubes of cytochrome C (cyto-c) with glutaraldehyde (GA) or PSS based on the
      layer-by-layer (LbL) assembly through covalent binding and electrostatic
      adsorption have been fabricated. The combination of the template method and the
      LbL method for fabrication of nanotubes exhibits low cost, simplicity, and
      versatility. The tubular morphology of the assembled glutaraldehyde and
      cytochrome C film was demonstrated by scanning electron microscopy (SEM) and
      transmission electron microscopy (TEM) measurements. The components of the tubes
      were determined by energy-dispersive X- ray spectra (EDAX). It is found that the
      assembled tubes keep the proteins' biochemical activity and electronic activity
      by cyclic voltammograms. The measurements of ultraviolet spectra and circular
      dichroism (CD) on the assembled nanotubes confirmed the cyto-c existence in the
      tubes.

PMID- 16961316
TI  - Designer protein-based performance materials.
AB  - Repeat sequence protein polymer (RSPP) technology provides a platform to design
      and make protein-based performance polymers and represents the best nature has to
      offer. We report here that the RSPP platform is a novel approach to produce
      functional protein polymers that have both biomechanical and biofunctional blocks
      built into one molecule by design, using peptide motifs. We have shown that
      protein-based designer biopolymers can be made using recombinant DNA technology
      and fermentation and offer the ability to screen for desired properties utilizing
      the tremendous potential diversity of amino acid combinations. The technology
      also allows for large-scale manufacturing with a favorable fermentative cost
      structure to deliver commercially viable performance polymers. Using three
      diverse examples with antimicrobial, textile targeting, and UV-protective agent,
      we have introduced functional attributes into structural protein polymers and
      shown, for example, that the functionalized RSPPs have possible applications in
      biodefense, industrial biotechnology, and personal care areas. This new class of
      biobased materials will simulate natural biomaterials that can be modified for
      desired function and have many advantages over conventional petroleum-based
      polymers.

PMID- 16961317
TI  - Synthesis and characterization of biocompatible polymer interlayers on titanium
      implant materials.
AB  - A bifunctional copolymer series of (4-vinylbenzyl)phosphonic acid diethylester
      and N-acryloxysuccinimide was developed as an interlayer with the aim of
      immobilizing proteins on titanium surfaces. Copolymers with varying compositions
      were synthesized, and an alternating copolymerization of the two monomers was
      found. The copolymers form ultrathin films of about 2-8 nm on titanium surfaces
      in a simple dipping process, as estimated from the attenuation of the titanium X
      ray photoelectron spectroscopy (Ti-XPS) signal. The films were characterized by
      infrared spectroscopy, XPS, and time-of-flight secondary ion mass spectrometry.
      The results indicate that the immobilization is due to phosphonate groups, and
      thus the phosphonate content of the copolymers is decisive for the final film
      thickness. These polymer films were examined for their potential protein binding
      capacity by using trifluoroethylamine derivatization and subsequent XPS analysis
      as a reactivity assay.

PMID- 16961318
TI  - Quantification and confocal imaging of protein specific molecularly imprinted
      polymers.
AB  - We have employed FITC--albumin as the protein template molecule in an aqueous
      phase molecular imprinted polymer (HydroMIP) strategy. For the first time, the
      use of a fluorescently labeled template is reported, with subsequent
      characterization of the smart material to show that the HydroMIP possesses a
      significant molecular memory in comparison to that of the nonimprinted control
      polymer (HydroNIP). The imaging of the FITC--albumin imprinted HydroMIP using
      confocal microscopy is described, with the in situ removal of the imprinted
      protein displayed in terms of observed changes in the fluorescence of the
      imprinted polymer, both before and after template elution (using a 10% SDS/10%
      AcOH (w/v) solution). We also report the imaging of a bovine hemoglobin (BHb)
      imprinted HydroMIP using two-photon confocal microscopy and describe the effects
      of template elution upon protein autofluorescence. The findings further
      contribute to the understanding of aqueous phase molecular imprinting protocols
      and document the use of fluorescence as a useful tool in template
      labeling/detection and novel imaging strategies.

PMID- 16961319
TI  - Water-soluble poly(ethylenimine)-based nitric oxide donors: preparation,
      characterization, and potential application in hemodialysis.
AB  - A novel approach to potentially resolve serious thrombosis issues associated with
      kidney dialysis (hemodialysis) therapies is described. New water-soluble
      polymeric nitric oxide (NO) donors, based on the diazeniumdiolated branched
      poly(ethylenimine)s and their derivatives, are prepared and characterized. These
      macromolecular NO donors (with up to 4.15 micromol/mg of total NO release) are
      utilized as additives to the dialysate solution of model dialysis filters. The
      presence of these species can create a localized increase in NO levels at the
      high surface area dialysis fiber/blood interface within the hemodialyzers. Nitric
      oxide is a naturally occurring and potent anti-platelet agent and is expected to
      greatly decrease the risk of thrombosis in the dialysis units.

PMID- 16961320
TI  - Molecular orientation distributions in a biaxially oriented poly(L-lactic acid)
      film determined by polarized Raman spectroscopy.
AB  - Molecular orientation distributions in the crystalline and amorphous regions of a
      biaxially oriented poly(L-lactic acid) film were analyzed fully by polarized
      Raman spectroscopy. Raman bands at 926 and 875 cm(-1) were chosen for the
      determination of the most probable molecular orientation distribution functions
      for the crystalline and amorphous regions in the film. It was revealed that the
      PLLA molecules were oriented biaxially in both the crystalline and amorphous
      regions. The orientation distribution normal to the film surface was found to be
      broader in the amorphous regions than in the crystalline regions. Furthermore, a
      predominant unidirectional molecular orientation was observed in the crystalline
      regions, whereas the molecular orientation distribution in the amorphous regions
      was isotropic in the plane parallel to the film surface. The different behavior
      of the crystalline and amorphous regions suggests that each region underwent
      different deformation mechanisms during the film formation.

PMID- 16961321
TI  - Kinetics of enzymatic depolymerization of guar galactomannan.
AB  - A new mathematical model based on Michaelis Menten (MM) kinetics is developed to
      predict the changes in molecular weight distribution (MWD) during the enzymatic
      depolymerization of guar galactomannan. The model accounts for the effect of
      branching by considering the guar molecule as a substrate having three types of
      bonds with different MM kinetic parameters. The overall kinetics of the enzymatic
      reactions then can be represented in terms of composite kinetic parameters that
      are functions of the MM parameters for the individual bonds. The depolymerization
      is assumed to follow a random scission mechanism, in which an enzyme randomly
      attacks the substrate molecule at any one of the three types of bonds, and leaves
      the substrate on cleavage of the bond. Expressions for the variation in molecular
      weights during depolymerization are developed by applying moment generating
      techniques to the kinetic model. The model is evaluated against the complete MWD
      obtained using gel permeation chromatography. During the initial stages of
      depolymerization, the enzymatic reaction is in the zero-order regime of MM
      kinetics and the polydispersity index (PDI) increases with time. Subsequently,
      the PDI decreases as the depolymerization tends to follow first order kinetics.
      We also show that for a zero-order, random or nonrandom scission, the variation
      of PDI with time can exhibit a maximum. These analyses confirm that an increase
      in PDI during the depolymerization is not necessarily due to nonrandom scission,
      as previously concluded.

PMID- 16961322
TI  - Synthesis and hemocompatibility of biomembrane mimicing poly(carbonate urethane)s
      containing fluorinated alkyl phosphatidylcholine side groups.
AB  - In this article, we designed and synthesized biomembrane mimicing segmented
      poly(carbonate urethane)s containing fluorinated alkyl phosphatidylcholine (PC)
      side groups. To obtain these novel poly(carbonate urethane)s, a new diol with a
      long side chain fluorinated alkyl phosphatidylcholine polar headgroup (2-[2
      2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9-hexadecafluoro-10-ethoxy-decyloxy-N-(2-hydroxy-1
      hydroxymethyl-1-methyl-ethyl)-acetamide] phosphatidylcholine, HFDAPC) was first
      synthesized and characterized. Then a series of poly(carbonate urethane)s
      containing fluorinated alkyl phosphatidylcholine side groups were synthesized
      using methylenebis(phenylene isocyanate) (MDI), poly(1,6-hexyl-1,5-pentyl
      carbonate) diol (PHPCD), 1,4-butandiol (BDO), and HFDAPC. The obtained
      fluorinated phosphatidylcholine poly(carbonate urethane)s (FPCPCU) possessed high
      molecular weight, narrower molecular weight distribution, and good mechanical
      properties as characterized by GPC and Instron, showing an increased
      hydrophilicity and a possible arrangement of surface structure as characterized
      by water contact angle. XPS results indicated that the phosphatidylcholine polar
      headgroups have been indeed pulled out to the surface with the help of the
      migration of the fluorinated side chain that was directly connected with the
      phosphatidylcholine polar headgroup. A preliminary result by protein adsorption
      and platelet adhesion experiments suggested that only 5 approximately 12.5 mol %
      phosphatidylcholine could be enough for good hemocompatibility. The current work
      demonstrates a new synthetic approach that can be used to bring the bioactive PC
      groups to the surface of the PC-containing polyurethanes more effectively.

PMID- 16961323
TI  - Incorporation of alpha-amylase enzyme and a bioactive filler into hydrophilic,
      partially degradable, and bioactive cements (HDBCs) as a new approach to tailor
      simultaneously their degradation and bioactive behavior.
AB  - Hydrophilic, partially degradable, and bioactive cements (HDBCs) are starch
      containing cements intended to degrade partially in the human body and, in so
      doing, allow for bone ingrowth inside the pores formed during degradation.
      Therefore, the study of degradation and bioactivity behavior was performed to
      assess the suitability of the current HDBCs formulations to achieve those aims.
      The degradation profile of HDBCs was studied under different conditions,
      including incubation in phosphate-buffered saline (PBS) and PBS supplemented with
      alpha-amylase at different concentrations. Thermostable alpha-amylase was also
      added to some formulations to allow control of the degradation rate and its
      extent. In a second stage the simultaneous phenomena of enzymatic degradation and
      bioactivity (both in vitro) was studied. We observed that the degradation of
      starch present in HDBCs can be easily controlled by the amount of alpha-amylase
      added to the cement and high values of degradation may be achieved if high enough
      quantities of enzyme are incorporated. However, the maximum degradation extent is
      much more dependent on the total amount of starch present in the formulation than
      on the amount of enzyme added to it: for full pore connectivity, the amount of
      starch should be higher than the percolation threshold for a 3D specimen.
      Nonetheless, calcium phosphate was able to nucleate and spread in inner pores of
      the cement, formed due to degradation, if they were interconnected. For a more
      thorough covering of the pores with calcium phosphates the amount of starch
      present in HDBCs should be increased to be higher than the percolation threshold.

PMID- 16961325
TI  - Conformational modifications of alpha gliadin and globulin proteins upon complex
      coacervates formation with gum Arabic as studied by Raman microspectroscopy.
AB  - As a molecular model of gelatin-free coacervates, complexes of pea globulin and
      alpha gliadin proteins with gum arabic prepared at different acidic pH values are
      studied using Raman microspectrometry. Raman spectra confirm higher content of
      beta-sheets and random coils in pea globulin and dominating alpha-helical
      structures in alpha gliadin. For protein-gum arabic complexes, Raman data support
      the existence of specific pH conditions for optimal complex coacervation (pH 2.75
      for globulin and pH 3.0 for gliadin(1)), when (i) pH-induced conformational
      perturbations of free protein structure are the strongest and (ii) compensation
      of these perturbations by gum arabic is the most pronounced. Conformations
      implied in the protein-gum complexes are mainly beta-sheets in pea globulin and
      alpha-helix in alpha gliadin. The role of electrostatic and non-Coulombic
      interactions (intermolecular hydrogen bonds) in stabilizing of protein
      polysaccharide complexes is discussed in relation with the overall structure and
      the charge density profile of these two proteins.

PMID- 16961324
TI  - Glutaraldehyde cross-linking of lipases adsorbed on aminated supports in the
      presence of detergents leads to improved performance.
AB  - Lipases from Candida rugosa (CRL) and lipase isoforms A and B from Candida
      antarctica (CAL-A and CAL-B) were adsorbed on aminated supports in the presence
      of detergents to have individual lipase molecules. Then, one fraction was washed
      to eliminate the detergent, and both preparations were treated with
      glutaraldehyde. The presence of detergent during the cross-linking of the lipases
      to the support permitted an increase in the recovered activity (in some
      instances, even by a 10-fold factor). This activity was higher even than that
      exhibited by the just adsorbed lipases, suggesting that it was not a result of
      some protective effect of the detergent in the enzyme activity during
      glutaraldehyde chemical modification. Moreover, the enantioselectivity of the
      different enzyme preparations was very different if the glutaraldehyde was
      offered in the presence or in the absence of detergent, in some cases increasing
      the E value (even by a 7-fold factor in the case of CAL-A in the hydrolysis of
      (+/-)-2-hydroxy-4-phenylbutyric acid ethyl ester), in other cases even inverting
      the enantio preference (e.g., in the case of CRL). The irreversible chemical
      inhibition of the enzyme that was immobilized and cross-linked with
      glutaraldehyde in the presence of detergents was more rapid than that in the
      other preparations (by more than a 10-fold factor). This experiment reveals an
      exposition degree of the active serine in the preparation cross-linked with the
      support in the presence of detergent that is higher than that in the other
      preparations. The results suggested that different enzyme structures were
      "stabilized" by the glutaraldehyde treatment if performed in the presence or in
      the absence of detergent, and that, in the presence of detergent, a form of the
      lipase with the serine residue more exposed to the medium and much more active
      could be obtained. This strategy seems to be of general use to improve the lipase
      activity to be used in macroaqueous media.

PMID- 16961326
TI  - Gelatinization of starch in excess water: beyond the melting of lamellar
      crystallites. A combined wide- and small-angle X-ray scattering study.
AB  - The gelatinization of waxy rice, regular rice, and potato starch suspensions (66%
      w/w moisture) was investigated by real-time small-angle X-ray scattering (SAXS)
      and wide-angle X-ray diffraction (WAXD) during heating and by fast ramp
      differential scanning calorimetry (DSC). The high-angle tail of the SAXS patterns
      suggested the transition from surface to mass fractal structures in the DSC
      gelatinization range. Amylose plays a major role in determining the dimensions of
      the self-similar structures that develop during this process as the
      characteristic power-law scattering behavior extends to lower scattering angles
      for regular than for waxy starches. Crystallinity of A-type starches is lost in
      the temperature region roughly corresponding to the DSC gelatinization range. At
      the end of the gelatinization endotherm, the B-type potato starch showed residual
      crystallinity (WAXD), while SAXS-patterns exhibited features of remaining
      lamellar stacks. Results indicate that the melting of amylopectin crystallites
      during gelatinization is accompanied by the (exothermic) formation of amorphous
      networks.

PMID- 16961328
TI  - Acacia senegal gum: continuum of molecular species differing by their protein to
      sugar ratio, molecular weight, and charges.
AB  - The main chemical and physical features of the Acacia senegal exudate gum and its
      molecular fractions isolated by chromatographies were determined using a wide
      variety of methods. Three main molecular fractions were isolated after
      hydrophobic interaction chromatography (HIC) and biochemical analyses confirmed
      the presence of an arabinogalactan-peptide (FI), an arabinogalactan-protein
      (FII), and a glycoprotein (FIII) fraction as described commonly in the
      literature. Further purification of FIII using size exclusion chromatography
      revealed three distinct populations. A wide molecular weight distribution within
      each population with the presence of at least two distinct molecular species per
      population was identified by high performance size exclusion chromatography
      coupled to on line multi-angle laser light scattering (HPSEC-MALLS). In addition,
      both sugars content (neutral and uronic acids) and UV profiles revealed that FIII
      was composed of a continuum of molecular species differing both by their protein
      to-sugar ratio and molecular weight. FI and FII had average molecular weight M(w)
      of 2.86 x 10(5) and 1.86 x 10(6) g.mol(-1), respectively, and a low
      polydispersity index (M(w)()/M(n) approximately 1.3). The three populations
      identified in FIII after HIC separation had M(w) of 2.67 x 10(6), 7.76 x 10(5),
      and 2.95 x 10(5) g.mol(-1) and very low polydispersity indexes (1.13, 1.04, and
      1.01). Estimation of the polypeptide backbone length in the three fractions gave
      43, 2253, and 4443 amino acid residues, respectively, hydroxyproline (Hyp) and
      serine being the most prominent residues within FI and FII, Hyp and Asx
      (asparagine + aspartic acid) within FIII. Secondary structure prediction from
      circular dichroism data resulted in polyproline II, beta-sheet, and random coil
      structures for FII and FIII, whereas no secondary structure was identified in FI.
      The existence of exposed tryptophanyl residues to the solvent was noticed by
      fluorescence in FII and FIII, tryptophan residues being absent from FI. In
      addition, 8-5' non cyclic diferulic acid was identified to be covalently linked
      to carbohydrate moieties of FII. Infrared spectroscopy identified the different
      vibrations of saccharidic and peptidic bonds with absorbance amplitudes in
      agreement with sugar and protein elementary analyses. Titration measurements in
      order to evaluate the number of charges on total Acacia gum and its molecular
      fractions revealed that 100% of charges came from polysaccharidic moieties (i.e.,
      glucuronic acids) in FI. Charges coming from polysaccharidic moieties were of
      91.3% and 37.9% for FII and FIII, respectively, the remaining 8.7% and 62.1%
      charges in FII and FIII molecular fractions coming from the polypeptidic
      backbone.

PMID- 16961327
TI  - Application of a microfluidic reactor for screening cancer prodrug activation
      using silica-immobilized nitrobenzene nitroreductase.
AB  - The nitroreductase-catalyzed conversion of a strong electron-withdrawing nitro
      group to the corresponding electron-donating hydroxylamine is useful in a variety
      of biotechnological applications. Activation of prodrugs for cancer treatments or
      antibiotic therapy are the most common applications. Here, we show that a
      bacterial nitrobenzene nitroreductase (NbzA) from Pseudomonas pseudoalcaligenes
      JS45 activates the dinitrobenzamide cancer prodrug CB1954 and the proantibiotic
      nitrofurazone. NbzA was purified by affinity chromatography and screened for
      substrate specificity with respect to prodrug activation. To facilitate screening
      of alternate potential prodrugs, polyethyleneimine-mediated silica formation was
      used to immobilize NbzA with high immobilization yields and high loading
      capacities. Greater than 80% of the NbzA was immobilized, and enzyme activity was
      significantly more stable than NbzA in solution. The resulting silica
      encapsulated NbzA was packed into a microfluidic microreactor that proved
      suitable for continuous operation using nitrobenzene, CB1954, and the
      proantibiotic nitrofurazone. The flow-through system provides a rapid and
      reproducible screening method for determining the NbzA-catalyzed activation of
      prodrugs and proantibiotics.

PMID- 16961329
TI  - Synthesis and characterization of new micrometer-sized radiopaque polymeric
      particles of narrow size distribution by a single-step swelling of uniform
      polystyrene template microspheres for X-ray imaging applications.
AB  - Radiopaque micron-sized non-cross-linked polystyrene/poly(2
      methacryloyloxyethyl(2,3,5-triiodobenzoate)) particles of narrow size
      distribution were prepared by a single-step swelling of uniform polystyrene
      template microspheres with emulsion droplets of methylene chloride containing the
      initiator benzoyl peroxide and the iodinated monomer 2-methacryloyloxyethyl(2,3,5
      triiodobenzoate), followed by the polymerization of the monomer within the
      swollen template particles at 73 degrees C. Radiopaque micron-sized uniform cross
      linked polystyrene/poly(2-methacryloyloxyethyl(2,3,5-triiodobenzoate)
      divinylbenzene) composite particles were prepared similarly with emulsion
      droplets of methylene chloride containing divinylbenzene, in addition to the
      initiator and the iodinated monomer. Radiopaque micron-sized uniform cross-linked
      poly(2-methacryloyloxyethyl(2,3,5-triiodobenzoate)-divinylbenzene) particles were
      formed by dissolving the template polystyrene polymer belonging to the former
      cross-linked composite particles. Characterization of these novel radiopaque
      polymeric particles was performed by methods such as FTIR, TGA, DSC, SEM, XPS,
      elemental analysis, and light microscopy. The influence of the weight ratio [2
      methacryloyloxyethyl(2,3,5-triiodobenzoate)]/[polystyrene] and [2
      methacryloyloxyethyl(2,3,5-triiodobenzoate)]/[divinylbenzene] on the bulk and
      surface properties of the non-cross-linked and cross-linked particles,
      respectively was elucidated. The radiopacity of these iodinated particles was
      demonstrated by an imaging technique based on X-ray absorption usually used in
      hospitals. These novel radiopaque particles may be used for different X-ray
      imaging needs, e.g., blood pool, body organs, embolization, dental composition,
      implants, protheses, and nanocomposites.

PMID- 16961330
TI  - Self-assembly of monoglycerides in beta-lactoglobulin adsorbed films at the air
      water interface. Structural, topographical, and rheological consequences.
AB  - In this work, we have analyzed the structural, topographical, and surface
      dilatational characteristics of pure beta-lactoglobulin adsorbed films and the
      effect of the self-assembly of monoglycerides (monopalmitin or monoolein) in beta
      lactoglobulin films at the air-water interface. Measurements were performed in a
      single device that incorporates a Wilhelmy-type film balance, Brewster angle
      microscopy, and interfacial dilatational rheology. The structural and
      topographical characteristics of beta-lactoglobulin adsorbed and spread films are
      similar. However, the surface dilatational modulus of beta-lactoglobulin films
      shows a complex behavior depending on film formation. The self-assembly of
      monoglyceride in a beta-lactoglobulin adsorbed film has an effect on the
      structural, topographical, and dilatational properties of the mixed films,
      depending on the interfacial composition and the surface pressure (pi). At low
      pi, a mixed film of monoglyceride and beta-lactoglobulin may exist. At high pi
      (after the collapse of beta-lactoglobulin), the mixed films are dominated by
      monoglyceride molecules. However, the small amounts of collapsed beta
      lactoglobulin have a significant effect on the surface dilatational properties of
      the mixed films. Protein displacement by monoglyceride is higher for monopalmitin
      than for monoolein. However, some degree of interaction exists between proteins
      and monoglycerides, and these interactions are more evident in adsorbed films
      than in spread films.

PMID- 16961331
TI  - Mechanical degradation and changes in conformation of hydrophobically modified
      starch.
AB  - In this paper, we study the mechanical degradation and changes in conformation of
      a branched ultrahigh molar mass biomacromolecule, hydrophobically modified
      starch, as caused by high-pressure homogenization. The characterization was
      performed with asymmetrical flow field-flow fractionation (AsFlFFF) with
      multiangle light scattering (MALS) and refractive index detection. The starch
      which had been chemically modified with octenyl succinate anhydride (OSA) proved
      to be very large and polydisperse. Upon high-pressure homogenization, the molar
      mass and rms radius (r(rms)) decreased, and the extent of these changes was
      related to the turbulent flow conditions during homogenization. The treatment
      also induced an increase and scaling with size in the apparent density of the
      macromolecules. To further study the changes in conformation, it was necessary to
      calculate the hydrodynamic radii (r(h)). This can be determined numerically from
      the elution times in the analysis and the flow conditions in the AsFlFFF channel.
      The results showed that the treatment can cause a dramatic decrease in the
      quotient between r(rms) and r(h), suggesting major conformational changes. These
      results together could be interpreted as degradation and "crumpling" of the
      macromolecule, which would give a decrease in r(rms) and an increase in apparent
      density, together with a "fraying" of more outer parts of the macromolecule,
      which could give rise to the increase in r(h).

PMID- 16961332
TI  - Effects of molecular structure of the resins on the volumetric shrinkage and the
      mechanical strength of dental restorative composites.
AB  - To prepare a dental composite that has a low amount of curing shrinkage and
      excellent mechanical strength, various 2,2-bis[4-(2-hydroxy-3-methacryloyloxy
      propoxy) phenyl] propane (Bis-GMA) derivatives were synthesized via molecular
      structure design, and afterward, properties of their mixtures were explored. Bis
      GMA derivatives, which were obtained by substituting methyl groups for hydrogen
      on the phenyl ring in the Bis-GMA, exhibited lower curing shrinkage than Bis-GMA,
      whereas their viscosities were higher than that of Bis-GMA. Other Bis-GMA
      derivatives, which contained a glycidyl methacrylate as a molecular end group
      exhibited reduced curing shrinkage and viscosity. Methoxy substitution for
      hydroxyl groups on the Bis-GMA derivatives was performed for the further
      reduction of the viscosity and curing shrinkage. Various resin mixtures, which
      had the same viscosity as the commercial one, were prepared, and their curing
      shrinkage was examined. A resin mixture containing 2,2-bis[3,5-dimethyl, 4-(2
      methoxy-3-methacryloyloxy propoxy) phenyl] propane] (TMBis-M-GMA) as a base resin
      and 4-tert-butylphenoxy-2-methyoxypropyl methacrylate (t-BP-M-GMA) as a diluent
      exhibited the lowest curing shrinkage among them. The composite prepared from
      this resin mixture also exhibited the lowest curing shrinkage along with enhanced
      mechanical properties.

PMID- 16961333
TI  - Vibrational spectroscopy of biopolymers under mechanical stress: processing
      cellulose spectra using bandshift difference integrals.
AB  - Mechanical stretching of covalent bonds, for example when a fibrous polymer is
      loaded in tension, results in their stretching vibrational bands in the infrared
      or Raman spectrum being shifted to lower frequency. Conversely stretching a
      hydrogen bond shifts the stretching vibrational mode of the donor covalent X-H
      bond to higher frequency. These band shifts are small and difficult to detect in
      complex regions of the spectrum where differently affected bands overlap. This
      paper describes a method of integrating the difference spectra (spectrum under
      tensile strain minus spectrum at zero tensile strain) to recover the shape of the
      bands that are shifted and the spectral variation in bandshift. The application
      of this method to two sets of vibrational spectra of cellulose under tension is
      described. In one example, C-O-C stretching bands of highly crystalline tunicate
      cellulose were observed to shift to lower frequency under axial strain. In the
      other example, a group of overlapping O-D stretching bands in partially
      deuterated cellulose showed varied bandshifts under axial strain, some bandshifts
      being positive as expected due to extension of axially oriented hydrogen bonds
      while others were negative. The possibility of constructing spectral plots of
      bandshift has the potential to clarify the interpretation of overlapped, shifting
      bands in the vibrational spectra of polymers under tension.

PMID- 16961334
TI  - Novel biobased nanocomposites from soybean oil and functionalized organoclay.
AB  - Novel biobased nanocomposites have been prepared by the cationic polymerization
      of conjugated soybean oil (CSOY) or conjugated LoSatSoy oil (CLS) with styrene
      (ST) and divinylbenzene (DVB), and a reactive organomodified montmorillonite
      (VMMT) clay as a reinforcing phase. This filler has been prepared by the cationic
      exchange of sodium montmorillonite with (4-vinylbenzyl)triethylammonium chloride
      in aqueous solution. The nanostructures of the nanocomposites have been
      determined by using wide-angle X-ray diffraction (WAXD) and transmission electron
      microscopy (TEM), respectively. The results from WAXD and TEM indicate that a
      heterogeneous structure consisting of intercalation and partial exfoliation or an
      intercalation structure exists in the nanocomposites, depending on the amount of
      VMMT in the polymer matrix. The thermal, mechanical, and organic vapor barrier
      properties of the nanocomposites have been evaluated by dynamic thermal analysis,
      thermogravimetric analysis, mechanical testing, and toluene absorption. A
      significant improvement is observed in the thermal stability, the dynamic bending
      storage modulus, the compressive modulus, the compressive strength, the
      compressive strain at failure, and the vapor barrier performance for the CSOY--
      and CLS-based nanocomposites with 1-2 wt % VMMT loading, where some individual
      exfoliated silicate platelets occur. For example, the CLS-based nanocomposite
      with 1-2 wt % VMMT exhibits increases of 100-128%, 86-92%, and 5-7% in
      compressive modulus, compressive strength, and compressive strain at failure,
      respectively. CLS with higher unsaturation and reactivity affords nanocomposites
      with higher thermal stability and higher mechanical properties than CSOY.

PMID- 16961336
TI  - Solution-liquid-solid growth of semiconductor nanowires.
AB  - The serendipitously discovered solution-liquid-solid (SLS) mechanism has been
      refined into a nearly general synthetic method for semiconductor nanowires.
      Purposeful control of diameters and diameter distributions is achieved. The
      synthesis proceeds by a solution-based catalyzed-growth mechanism in which
      nanometer-scale metallic droplets catalyze the decomposition of metallo-organic
      precursors and crystalline nanowire growth. Related growth methods proceeding by
      the analogous vapor-liquid-solid (VLS) and supercritical fluid-liquid-solid
      (SFLS) mechanisms are known, and the relative attributes of the methods are
      compared. In short, the VLS method is most general and appears to afford
      nanowires of the best crystalline quality. The SLS method appears to be
      advantageous for producing the smallest nanowire diameters and for variation and
      control of surface ligation. The SFLS method may represent an ideal compromise.
      Recent results for SLS growth are summarized.

PMID- 16961337
TI  - Solution-based synthetic strategies for 1-D nanostructures.
AB  - One-dimensional (1-D) nanostructures of materials have received great research
      attention because of their unique photochemistry, photophysical, and electron
      transport properties different from those of bulky or nanoparticle materials. One
      of the main challenges in this field is how to precisely control the sizes,
      dimensionalities, compositions, and crystal structures of materials in nanoscale.
      This review summarizes the recent progress in the solution-based routes to
      prepare 1-D nanostructures, highlighting the contribution from this laboratory.
      Crystal structure as one of the inherent factors that may determine the growth
      behavior of the nanocrystals is emphasized in this paper. Particularly compounds
      with layered structures or anistropic crystal structures are given special
      attention in the controlled growth of 1-D nanostructures. This review aims to
      present a relatively general understanding of the correlation between the crystal
      structure and growth behavior of materials under solution-based conditions and
      show how to choose appropriate conditions for the growth of 1-D nanostructures.

PMID- 16961338
TI  - Solution-grown zinc oxide nanowires.
AB  - We review two strategies for growing ZnO nanowires from zinc salts in aqueous and
      organic solvents. Wire arrays with diameters in the nanoscale regime can be grown
      in an aqueous solution of zinc nitrate and hexamethylenetetramine. With the
      addition of poly(ethylenimine), the lengths of the wires have been increased to
      25 mum with aspect ratios over 125. Additionally, these arrays were made vertical
      by nucleating the wires from oriented ZnO nanocrystals. ZnO nanowire bundles have
      been produced by decomposing zinc acetate in trioctylamine. By the addition of a
      metal salt to the solution, the ZnO wires can be doped with a range of transition
      metals. Specifically, ZnO nanowires were homogeneously doped with cobalt and
      showed a marked deviation from paramagnetic behavior. We conclude by highlighting
      the use of these solution-grown nanowire arrays in dye-sensitized solar cells.
      The nanowire cells showed an improvement in the charge collection efficiency over
      traditional nanoparticle cells.

PMID- 16961339
TI  - One-dimensional colloidal gold and silver nanostructures.
AB  - One-dimensional (1-D) metallic nanoscale materials have long been of interest to
      many groups of scientists. Within the last 2 decades, great advances in the
      synthesis of metallic nanorods and nanowires have been made, with a variety of
      templating methods. More recently, bottom-up chemical syntheses of these
      materials have become increasingly reported in the literature. This Forum Article
      describes the synthesis, physical properties, and potential applications of 1-D
      metals, with an emphasis on silver and gold derived from studies in the authors'
      laboratories.

PMID- 16961340
TI  - Template-grown metal nanowires.
AB  - The growth of metal nanowires using membranes as hard templates is reviewed. The
      method provides access to arrays of single-crystal metal nanowires and to quasi
      one-dimensional metal nanostructures with controlled compositional variation
      along their length. Recent applications of these kinds of nanowires to problems
      in superconductivity, optical spectroscopy and sensing, and catalytic conversion
      of chemical to mechanical energy are reviewed.

PMID- 16961341
TI  - Stability and porosity enhancement through concurrent ligand extension and
      secondary building unit stabilization.
AB  - A trigonal nanosized carboxylate ligand, 1,3,5-tris[4'-carboxy(1,1'-biphenyl-4
      yl)]benzene (TCBPB), has been synthesized and applied in the construction of
      porous metal-organic frameworks (MOFs). A solvothermal reaction of TCBPB and a
      zinc salt in the presence of pyridine produces 1, an unstable MOF consisting of a
      tetrazinc secondary building unit (SBU) with labile terminal ligands. Changing
      pyridine to a noncoordinating base in the assembly procedure affords 2, a stable
      MOF with permanent porosity containing an octazinc SBU without labile terminal
      ligands.

PMID- 16961342
TI  - Ancillary ligand functionalization of cyanide-bridged S = 6 Fe(III)4Ni(II)4
      complexes for molecule-based electronics.
AB  - Treatment of 1-chloro-6-iodohexane or 1-chloro-10-iododecane with lithium
      tris(pyrazolyl)methanide, followed by potassium thioacetate, affords bifunctional
      1-S(acetyl)-tris(pyrazolyl)alkanes (L) (pz)3C(CH2)nSAc (n = 6, 1; 10, 2).
      Magnetic studies of {[(pzTp)Fe(III)(CN)3]4[Ni(II)L]4[OTf]4}.solvent (4, L = 1; 5,
      L = 2) boxes suggest that -(CH2)6 chains (4) limit intermolecular interactions
      while -(CH2)10 chains in 5 introduce crystallographic disorder and a distribution
      of relaxation times; 4 and 5 exhibit slow relaxation of the magnetization.

PMID- 16961343
TI  - Mechanistic studies of Hangman salophen-mediated activation of O-O bonds.
AB  - Stopped-flow kinetic studies of a HSX-Mn-SalophOMe (1) catalyst provide
      spectroscopic evidence for the direct generation of a manganese(V) oxo salophen
      from a manganese(III) perbenzoate. The O-O bond heterolysis reaction that
      produces the oxo is not facilitated by intramolecular proton transfer from the
      acid hanging group of the HSX platform. Instead, the hanging group stabilizes the
      catalyst against oxidative degradation and, consistent with recent predictions of
      theory, is geometrically matched to promote the end-on coordination of a H2O2
      substrate prior to its oxidation at the manganese(V) oxo center.

PMID- 16961344
TI  - Antiferromagnetic interaction achieved by a 3-D supramolecular CuII complex with
      pyrazino-fused TTF as the ligand, [CuCl2(BP-TTF)].
AB  - The diffusion reaction of TBA2Cu(II)Cl4 (TBA = tetrabutylammonium) and a N
      containing organic donor, BP-TTF [=bis(pyrazino)tetrathiafulvalene], yielded a 3
      D supramolecular Cu complex, [CuCl2(BP-TTF)] (1). The magnetic measurement of 1
      exhibits an antiferromagnetic interaction by fitting a Bonner-Fisher model from 2
      to 300 K with S = 1/2 and J = -3.5 K between Cu(IotaIota) mediated by self
      assembling donor columns.

PMID- 16961345
TI  - Chirality and magnetism in a novel series of isotypic borophosphates:
      M(II)[BPO4(OH)2] (M(II) = Mn, Fe, Co).
AB  - Three novel isotypic borophosphates M(II)[BPO4(OH)2] (M(II) = Mn, Fe, Co) have
      been hydrothermally synthesized and structurally characterized. The isotypic
      compounds crystallize in the chiral space group P3(1)21 or P3(2)21. Their crystal
      structures are characterized by edge-sharing helical M(II)O6-octahedral chains
      wound around 3(1) or 3(2) screw axes (along [001]) interconnected by
      borophosphate single chains of alternating BO2(OH)2 and PO4 tetrahedra
      perpendicular to [001], resulting in three-dimensional framework structures. The
      helical M(II)O6-octahedral chains lead to low-dimensional magnetic properties.

PMID- 16961347
TI  - 1D helical polymeric chain with a pseudo-5(3) screw axis formed by
      cuprophilicity. synthesis and crystal structure of copper(I) pivalate.
AB  - A coordination polymer, [Cu5(piv)5]n (piv = pivalate), was prepared by a thermal
      decomposition method. The unit cell of the crystal structure consisted of one
      right-handed helical chain and one left-handed helical chain, which were formed
      by an alternation of Cu(I) ions and carboxylate (O-C-O) groups. This chain
      possessed a pseudo-5(3) screw axis; the second-order structure was suggested to
      be realized by a balance between the cuprophilicity and a steric effect of the
      tert-butyl groups.

PMID- 16961346
TI  - Active-site models of bacterial nitric oxide reductase featuring tris-histidyl
      and glutamic acid mimics: influence of a carboxylate ligand on Fe(B) binding and
      the heme Fe/Fe(B) redox potential.
AB  - Active-site models of bacterial nitric oxide reductase (NOR) featuring a heme Fe
      and a trisimidazole- and glutaric acid-bound non-heme Fe (Fe(B)) have been
      synthesized. These models closely replicate the proposed active site of native
      NORs. Examination of these models shows that the glutamic acid mimic is required
      for both Fe(B) retention in the distal binding site and proper modulation of the
      redox potentials of both the heme and non-heme Fe's.

PMID- 16961348
TI  - Thermotropic mesomorphism of soft materials bearing carboxylate-supported mu4-oxo
      tetracupric clusters.
AB  - A new ligand containing long alkyl (octadecyl) chains was used to obtain the
      mesogenic complex [L2Cu4(mu4-O)(OAc)4].EtOH (1). This complex was thoroughly
      characterized and had its molecular structure solved by X-ray diffraction (XRD).
      Mesomorphic properties were demonstrated by means of polarized microscopy,
      differential scanning calorimetry, and XRD.

PMID- 16961349
TI  - Coordination of fluoro ligands toward sodium ions makes the difference: aqua
      sodium ions act as Bronsted acids in polymerization of vinyl ethers and styrenes.
AB  - In searching for aqua sodium species acting as Bronsted acids in catalysis, we
      explored the phenomenon that sodium tetrakis[3,5
      bis(trifluoromethyl)phenyl]borate dihydrate (NaBAr(F)4.2H2O) evidently provides
      one proton source to initiate the polymerization of vinyl ethers in anhydrous
      dichloromethane solutions. In addition, NaBAr(F)4 catalyzed efficiently in the
      polymerization of activated styrenes, such as p-methoxystyrene.

PMID- 16961350
TI  - New members in the Ni(n+1)(QO3)nX2 family: unusual 3D network based on Ni4ClO3
      cubane-like clusters in Ni7(TeO3)6Cl2.
AB  - Three new members in the family of nickel(II) tellurium(IV)/selenium(IV)
      oxyhalides generally formulated as Ni(n+1)(QO3)nX2 (Q = Te, X = Cl, n = 6, 10; Q
      = Se, X = Br, n = 4) have been synthesized by solid-state reactions of NiX2, QO2,
      and NiO (or Ni2O3) at high temperature. The structure of Ni7(TeO3)6Cl2 features a
      novel 3D network based on Ni4ClO3 cubane-like clusters with Te atoms located at
      the cavities of the network. Ni4ClO3 clusters are interconnected into a hexagonal
      layer through additional O...O edges. The neighboring two layers are further
      interconnected, via sharing of common Ni(II) atoms, into a novel 3D network. The
      3D open framework of Ni5(SeO3)4Br2 is built from 2D nickel(II) oxybromide layers
      bridged by Se and additional Ni atoms. The structure of Ni11(TeO3)10Cl2 features
      a condensed 3D network based on NiO5Cl, NiO6, and NiO5 polyhedra interconnected
      via corner and edge sharing, as well as O-Te-O bridges. The results of magnetic
      property measurements indicate that all three compounds display antiferromagnetic
      interactions between nickel(II) centers.

PMID- 16961351
TI  - Electronic structures and absorption spectra of linkage isomers of trithiocyanato
      (4,4',4' '-tricarboxy-2,2':6,2' '-terpyridine) ruthenium(II) complexes: a DFT
      study.
AB  - Black dye (BD), isomer 1 ([Ru(II)(H3-tctpy)(NCS)3](-1), where H3-tctpy = 4,4',4'
      '-tricarboxy-2,2':6,2' '-terpyridine) is known to be an excellent sensitizer for
      dye-sensitized solar cells and exhibits a very good near-IR photo response,
      compared to other ruthenium dyes. Because isothiocyanate is a linear ambidentate
      ligand, BD has three other linkage isomers, [Ru(H3-tctpy)(NCS)2(SCN)](-1), isomer
      2 and 2', and [Ru(H3-tctpy))(SCN)3](-1), isomer 3. In this study, we have
      calculated the geometry of BD and its isomers by DFT. Further, we have analyzed
      the bonding in these isomers using NBO methods. TDDFT calculations combined with
      scalar relativistic zero-order regular approximations (SR-ZORA) have been carried
      out to simulate the absorption spectra. Calculations have been performed for the
      isomers both in vacuo and in solvent (ethanol). The inclusion of the solvent is
      found to be important to obtain spectra in good agreement with the experiment.
      The first absorption bands are dominated by the metal-to-ligand charge transfer
      (MLCT) and ligand-to-ligand charge transfer (LLCT).

PMID- 16961352
TI  - Tuning the structural and magnetic properties of thermally robust coordination
      polymers.
AB  - Thermally robust materials of the M(5-X-pyrimidin-2-olate)2 type [M = Co, X = Cl
      (1(Cl)), X = Br (1(Br)), X = I (1(I)); M = Zn, X = Cl (2(Cl)), X = Br (2(Br)), X
      = I (2(I))] have been synthesized. Their X-ray powder diffraction structural
      characterization has revealed that they crystallize as I2d diamondoid frameworks,
      isomorphous to those of the pristine [M(pyrimidin-2-olate)2]n analogues (1(H), M
      = Co; 2(H), M = Zn). The magnetic measurements of the 1(X) series at magnetic
      fields of 100, 300, and 5000 Oe reveal a weak ferromagnetic ordering taking place
      below the Neel temperature (T(N) approximately 20 K), arising from spin canting
      phenomena of the antiferromagnetically coupled cobalt centers. Moreover, magnetic
      hysteresis studies carried out on the 1(X) series at 2 K reveal a strong
      dependence of both the coercive field H(coer) (2500, 1000, 775, and 500 Oe for
      1(Br), 1(Cl), 1(I), and 1(H), respectively) and the remnant magnetization M(rem)
      (0.0501 mu(B) for 1(Br) and 1(Cl), 0.0457 mu(B) for 1(I), and 0.0358 mu(B) for
      1(H)) on the 5-substituent of the pyrimidin-2-olates. The molecular alloys [Co(5
      Y-pyrimidin-2-olate)2] (Y = Cl/Br, 1(Cl/Br)) and [Co(5-Y'-pyrimidin-2-olate)2]
      (Y' = Br/I, 1(Br/I)) have also been prepared and characterized, proving that they
      have intermediate properties. These materials combine interesting functional
      properties, such as chemical inertness, magnetism, photoluminescence, and
      (although weak) SHG activity.

PMID- 16961353
TI  - Structural and magnetic properties of a complete halide series of Ni(II)
      complexes with a pyridine-containing 14-membered macrocycle.
AB  - The complete halide series of Ni(II) complexes containing the tetradentate
      macrocyclic ligand 3,11-dithia-7,17-diazabicyclo[11.3.1]heptadeca-1(17),13,15
      triene (L), was fully characterized by X-ray diffraction. The fluoro, chloro, and
      bromo complexes are dinuclear species with formula [{Ni(L)}2(mu-X)2]2+ (X =
      halide), whereas only mononuclear species with formula [Ni(Y)(solv)(L)]n+ (Y =
      halide or solvent molecule), were obtained with I. To date, the fluoro derivative
      is the first nonorganometallic coordination compound containing the Ni(mu-F)2Ni
      core. The magnetic properties of these halo complexes have been studied.
      Intramolecular interactions were observed in the three dinuclear complexes, being
      antiferromagnetic in the fluoro derivative and ferromagnetic in both the chloro
      and bromo ones. The two iodo derivatives are paramagnetic species, as would be
      expected for mononuclear octahedral Ni(II) complexes. Density functional theory
      calculations led us to relate the magnetic behaviors of these compounds to the
      values of the corresponding Ni-X-Ni(i) angle. The analysis of the singly occupied
      molecular orbitals gave a clear comprehension of the different magnetic exchange
      interactions found in these Ni(II) complexes.

PMID- 16961354
TI  - Evolution of the structural chemistry of vanadium organodiphosphonate networks
      and frameworks: structural consequences of fluoride incorporation in the
      development of stable phases with void channels.
AB  - Hydrothermal reactions of solutions containing a vanadate source, an
      organodiphosphonate, an organonitrogen component, and HF (V/P/O/F) yield a series
      of oxyfluorovanadium-diphosphonates with charge-compensation provided by
      organoammonium cations or hydronium cations. While V/P/O/F networks provide the
      recurrent structural motif, the linkage between the layers and the details of the
      polyhedral connectivities within the layers are quite distinct for the five
      structures of this study. [H2pip][V4F4O2(H2O)2{O3P(CH2)3PO3}2] (1) (pip =
      piperazine) is a conventional three-dimensional (3D) "pillared" layer structure,
      whose V/P/O/F networks are buttressed by the propylene chains of the
      diphosphonate ligands. In contrast, [H2en][V2O2F2(H2O)2{O3P(CH2)4PO3}] (2) and
      [H2en]2[V6F12(H2O)2{O3P(CH2)5PO3}2 {HO3P(CH2)5PO3H}] (3) are two-dimensional (2D)
      slablike structures constructed of pairs of V/P/O/F networks sandwiching the
      pillaring organic tethers of the diphosphonate ligands. Despite the common
      overall topology, the layer substructures are quite different: isolated {VO5F}
      octahedra in 2 and chains of corner-sharing {VO(3)F(3)} octahedra in 3. The 3D
      structure of [H2en]2[V7O6F4(H2O)2{O3P(CH2)2PO3}4].7H2O (4.7H2O) exhibits a layer
      substructure that contains the ethylene bridges of the diphosphonate ligands and
      are linked through corner-sharing octahedral {VO6} sites. The connectivity
      requirements provide large channels that enclose readily removed water of
      crystallization. The structure of [H3O][V3F2(H2O)2{O3P(CH2)2PO3}2].3.5H2O
      (5.3.5H2O) is also 3D. Because of the similiarity with 4.7H2O, it exhibits
      V/P/O/F layers that include the organic tethers of the diphosphonates and are
      linked through corner-sharing {VO6} octahedra. In contrast to the network
      substructure of 4.7H2O, which contains binuclear and trinuclear vanadium
      clusters, the layers of 5.3.5 H2O are constructed from chains of corner-sharing
      {VO4F2} octahedra. Thermal studies of the open framework materials 4 and 5 reveal
      that incorporation of fluoride into the inorganic substructures provides robust
      scaffoldings that retain their crystallinity to 450 degrees C and above. In the
      case of 4, dehydration does not change the powder X-ray diffraction pattern of
      the material, which remains substantially unchanged to 450 degrees C. In the case
      of 5, there are two dehydration steps, that is, the higher temperature process
      associated with loss of coordinated water. This second dehydration results in
      structural changes as monitored by powder X-ray diffraction, but this new phase
      is retained to ca. 450 degrees C. The materials of this study exhibit a range of
      reduced oxidation states: 1 is mixed valence V(IV)/V(III) while 2 and 4.7H(2)O
      are exclusively V(IV) and 3 and 5.3.5H2O are exclusively V(III). These oxidation
      states are reflected in the magnetic properties of the materials. The
      paramagnetism of 1 arises from the presence of V(III) and V(IV) sites and
      conforms to the Curie-Weiss law with C = 2.38 em K/(Oe mol) and = -66 K with
      mu(eff) (300 K) = 4.33 mu(B). Compounds 3-5 exhibit Curie-Weiss law dependence of
      magnetism on temperature with mu(eff) (300 K) = 5.45 mu(B) for 3 (six V(III)
      sites), mu(eff) = 4.60 mu(B) for 4 (seven V(IV) sites) and mu(eff) = 4.13 mu(B)
      for 5 (two V(III) sites). Compound 2 exhibits antiferromagnetic interactions, and
      the magnetism may be described in terms of the Heisenberg linear
      antiferromagnetic chain model for V(IV). The effective magnetic moment at 300 K
      is 2.77 mu(B) (two V(IV) sites).

PMID- 16961355
TI  - Assembling of dimeric entities of Cd(II) with 6-mercaptopurine to afford one
      dimensional coordination polymers: synthesis and scanning probe microscopy
      characterization.
AB  - The direct reaction between 6-mercaptopurine (6-MP) and Cd(II) under different
      conditions yields either [Cd2(6-MP)4(NO3)2](NO3)2 (1) or [Cd(6-MP-)2.2H2O]n (4).
      Compound 1 behaves as the building block of the polymer [Cd(6-MP2-)2]n[Ca(H2O)6]n
      (3), by deprotonation of 6-MP ligand. In the reaction of 1 to give 3, the
      dinuclear compound [Cd2(6-MP)4(H2O)2](NO3)4.2H2O (2) can be isolated as an
      intermediate. Polymers 3 and 4 convert into each other in water via deprotonation
      protonation reactions. The structures of compounds 1-3 have been determined by X
      ray diffraction. Given the small differences in the arrangement shown in the
      crystal structures of the polymer 4 and the polyanion of 3, the stabilities and
      energetics of the two arrangements have been examined by DFT calculations to
      determine the possibility of identifying new conformations of both polymers. In
      addition, the two polymers have been characterized on surfaces by means of AFM.
      The direct reaction between 6-MP and Cd(II) and the deprotonation of the polymer
      4 have proven to be useful routes for the isolation of one-dimensional systems on
      surfaces. The development of new strategies to characterize these types of
      polymers on surfaces opens the possibility to perform nanoscale studies on their
      properties and their potential use as nanomaterials.

PMID- 16961356
TI  - Helices versus zigzag chains: one-dimensional coordination polymers of Ag(I) and
      Bis(4-pyridyl)amine.
AB  - Five one-dimensional coordination polymers were prepared by the reaction of a
      bent bridging ligand, bis(4-pyridyl)amine (bpa), with an extensive series of AgX
      salts (X = CF3SO3, PF6, ClO4, NO3). The 1D polymer networks formed with AgCF3SO3
      (1), AgPF6 (2.MeCN), and AgClO4 (3.2MeCN) all incorporated MeCN and were found to
      adopt a zigzag arrangement. The networks formed with AgClO4 (4) and AgNO3 (5) did
      not contain any solvent and adopted a single-stranded helical arrangement. Two
      dimensional H-bonding networks were formed for 1 and 3.2MeCN, with network
      topologies 4.8(2) and (4, 4), respectively, whereas three-dimensional H-bonded
      networks of helices were formed for 4, showing an (8, 3)-a network topology, and
      5, showing the topology of the alpha-polonium net. The three-dimensional networks
      both exhibited 4-fold interpenetration. The NO3- anion in 5 appeared to be acting
      as a template for the 3D structure.

PMID- 16961357
TI  - An unprecedented asymmetric end-on azido-bridged copper(II) imino nitroxide
      complex: structure, magnetic properties, and density functional theory analysis.
AB  - The dinuclear copper(II) complex [Cu2(mu(1,1)-N3)2(im-2py)2(N3)2] [im-2py = 2-(2
      pyridyl)-4,4,5,5-tetramethylimidazolinyl-1-oxy] has been prepared and
      structurally characterized. The crystal structure consists of a dinuclear unit in
      which the Cu(II) ions are bridged by two azido ions in a end-on asymmetric
      fashion and the imino nitroxide radicals are chelating by the two imino N atoms.
      Accordingly, the magnetic susceptibility data were analyzed considering a linear
      spin-coupling scheme rad(1)-Cu(2)-Cu(3)-rad(4) (with Si = 1/2, i = 1-4), where
      the Heisenberg spin Hamiltonian assumes the general form -2Sigma(i)<(j)S(i)S(j).
      Considering only first-neighbor spin-coupling constants (J13 = J24 = J14 = 0),
      magnetic susceptibility measurements show that the copper(II) imino nitroxide rad
      Cu-(Cu-rad)(rad-Cu)-Cu-rad exchange coupling is ferromagnetic and large (J12 =
      J34 = J1 > +190 cm(-1)), as is expected for copper imino nitroxide species, and
      the copper-copper (rad)-Cu-Cu-(rad) coupling through the asymmetric double end-on
      azide bridges appeared antiferromagnetic and rather large [J23 = J2 = -43(2) cm(
      1)]. By contrast, a density functional theory analysis of the system through the
      computation of broken-symmetry-state energies resulted in J2 approximately 0 cm(
      1). This apparent paradox is resolved by introducing a second-neighbor rad-(Cu)
      Cu-(rad)(rad)-Cu-(Cu)-rad spin-coupling constant J13 = J24 = J3, which turns out
      to be antiferromagnetic both experimentally (when J2 is set equal to zero) and
      computationally.

PMID- 16961358
TI  - Toward rational construction of gold, gold-silver, and gold-mercury string
      complexes: syntheses, structures, and properties of [Au(Tab)2]2L2 (L = I and
      PF6), {[(Tab)2M][Au(CN)2]}2 (M = Au and Ag), and {[Hg(Tab)2][Au(CN)2]2} [Tab = 4
      (trimethylammonio)benzenethiolate].
AB  - The reaction of AuI with 2 equiv of TabHPF6 [TabH = 4
      (trimethylammonio)benzenethiol] in the presence of excess Et3N in
      dimethylformamide (DMF)/MeOH afforded a binuclear gold(I) complex
      [Au(Tab)2]2I2.2H2O (1). Anion exchange of 1 with NH4PF6 in DMF gave rise to the
      more soluble complex [Au(Tab)2]2(PF6)2 (2). Treatment of 2 with K[Au(CN)2]
      produced a tetranuclear gold(I) complex {[(Tab)2Au][Au(CN)2]}2 (3). Analogous
      reactions of two known mononuclear complexes [Ag(Tab)2](PF6) (4) and
      [Hg(Tab)2](PF6)2 (5) with 1 or 2 equiv of K[Au(CN)2] generated one Ag2Au2 complex
      {[(Tab)2Ag][Au(CN)2]}2 (6) and one Au/Hg complex {[Hg(Tab)2][Au(CN)2]2} (7),
      respectively. Compounds 1-3, 6, and 7 were fully characterized by elemental
      analysis, IR spectra, UV-vis spectra, 1H NMR, and single-crystal X-ray
      crystallography. 1 and 2 have a similar [Au(Tab)2]2(2+) dimeric structure in
      which the two [Au(Tab)2]+ cations are connected via one Au-Au aurophilic
      interaction. In the structure of 3 or 6, each of the two pairs of [M(Tab)2]+
      cation and [Au(CN)2]- anion is held together via ionic interactions to form a
      {[(Tab)2M][Au(CN)2]} species (M = Au, 3; Ag, 6). Two such species are further
      connected by one Au-Au aurophilic bonding interaction to form an uncommon Au(4)
      or Ag2Au2 linear string structure with three ligand-unsupported metal-metal
      bonds. For 7, the [Hg(Tab)2]2+ dication and the [Au(CN)2]2(2-) dianion are
      interconnected by the secondary Hg...N(CN) interactions to form a 1D chain
      structure. The thermal and luminescent properties of 1-3, 6, and 7 in solid state
      were also investigated.

PMID- 16961359
TI  - Structural diversity in 4,4'-trimethylenedipyridine-zinc phosphite hybrids:
      incorporation of neutral guest molecules in hybrid materials.
AB  - Six new zinc phosphite hybrids are prepared under a variety of reaction
      conditions from the primary building blocks, trimethylenedipyridine, zinc
      acetate, and phosphorous acid. Neutral guest molecules are incorporated into
      several of the structures. Under hydrothermal conditions at 130 degrees C, an
      anionic framework structure, 1, templated on trimethylenedipyridinium, is
      obtained while a neutral ladder structure, 2, is formed at room temperature.
      These reactions are done at an initial pH of 4.7-5.0. When the reaction is done
      at an initial pH of 7.8-8.0, a neutral layered motif is obtained with 1,3
      dipyridylpropane pillars and neutral guests in the interstitial space. Structures
      with water, phenol, and catechol as the guests, compounds 3, 4, and 5,
      respectively, are reported. The use of catechol as a template results in the
      breakup of the ZnPO sheet structure common to both 3 and 4. When amino acids,
      including alanine, were added to the reaction medium, a neutral three-dimensional
      framework, 6, is obtained with no incorporation of the potential template. The
      syntheses and structures of these new materials are reported.

PMID- 16961360
TI  - Dimethylammonium trichlorocuprate(II): structural transition, low-temperature
      crystal structure, and unusual two-magnetic chain structure dictated by
      nonbonding chloride-chloride contacts.
AB  - Catena(dimethylammonium-bis(mu2-chloro)-chlorocuprate), (CH3)2NH2CuCl3, forms
      chains of Cu2Cl6(2-) bifold dimers linked along the structural chain axis by
      terminal chlorides forming long semicoordinate bonds to adjacent dimers. The
      structural chains are separated by dimethylammonium ions that hydrogen bond to
      chloride ions of the dimers. A structural phase transition below room temperature
      removes disorder in the hydrogen bonding, leaving adjacent dimers along the chain
      structurally and magnetically inequivalent, with alternating ferromagnetic and
      antiferromagnetic pairs. The coupled dimers are magnetically isolated from each
      other along the structural chain axis by the long semicoordinate Cu-Cl bond.
      However, the dimers couple to like counterparts on adjacent chains via nonbonding
      Cl...Cl contacts. The result is two independent magnetic chains, one an
      alternating antiferromagnetic chain and the other an antiferromagnetic chain of
      ferromagnetically coupled copper dimers, which run perpendicular to the
      structural chains. This magnetostructural analysis is used to fit unusual low
      temperature (1.6 K) magnetization vs field data that display a two-step
      saturation. The structural phase transition is identified with neutron scattering
      and capacitance measurements, and the X-ray crystal structures are determined at
      room temperature and 84 K. The results appear to resolve long-standing confusion
      about the origins of the magnetic behavior of this compound and provide a
      compelling example of the importance of two-halide magnetic exchange.

PMID- 16961361
TI  - Ferromagnetic exchange interactions for Cu6(12+) and Mn6(12+) hexagons sandwiched
      by two B-alpha-[XW9O33]9- (X = As(III) and Sb(III)) ligands in D3d-symmetric
      polyoxotungstates.
AB  - Two novel Cu6 and Mn6 hexagon sandwiched polyoxometalates, [(CuCl)6(AsW9O33)2]12-
      (1a) and [(MnCl)6(SbW9O33)2]12- (2a), have been synthesized and characterized by
      X-ray single-crystal analysis and magnetic measurements. These complexes are D3d
      symmetric and were isolated as [n-BuNH3]+ salts from aqueous solutions: (n
      BuNH3)12[(CuCl)6(AsW9O33)2].6H2O (1), rhombohedral, R, a = 20.33(1) A, c =
      26.35(2) A, Z = 3 and (n-BuNH3)12[(MnCl)6(SbW9O33)2].6H2O (2). Six Cu (or Mn)
      atoms, each of which shows 5-fold coordination, make an approximately equatorial
      hexagon with a first-neighboring Cu...Cu (Mn...Mn) distance of 2.913(2) A
      (3.248(1) A) and a Cu-O-Cu (Mn-O-Mn) bond angle of 94.5(2) degrees (100.4(2)
      degrees ). The magnetic behavior investigated by magnetic susceptibility
      measurements shows the ferromagnetic exchange interactions with J/k = +12.7 K
      (J/hc = +8.82 cm(-1)) and a S = 3 ground state for 1 and J/k = +0.20 K (J/hc =
      +0.14 cm(-1)) and a S = 15 ground state for 2, when only J refers to the
      isotropic magnetic-exchange interactions for first-neighbor atoms of the
      approximately equilateral Cu6(12+) and Mn6(12+) hexagons. The single-crystal ESR
      spectroscopy of 1 under the orientation of the magnetic field along a Cu6
      hexagon's nearly 6-fold axis equal to the c axis on the variation of temperature
      supports the S = 3 ground state and allows an estimate of the zero-field (fine
      structure) energy separation between Sz = 0 and Sz = +/-1 of D = -0.182 K to be
      obtained.

PMID- 16961362
TI  - Hydrothermal synthesis and structural characterizations of two new germanates
      with a novel topological framework and unusual Ge4(OH)4 cubane.
AB  - Two new germanates, Ge7O12(OH)4 (C4N3H13)(0.5)(H2O)5 (1) and Ge7O12(OH)4(H2O)6
      (2) have been synthesized under hydrothermal conditions and characterized by IR
      spectroscopy, powder XRD, TG, and single-crystal X-ray diffraction. Compound 1
      crystallizes in cubic space group P3m (No. 215) with a = b = c = 7.7119(5) A, v =
      458.65(5) A(3), z = 1. Compound 2: cubic, P3m, a = b = c = 7.7653(17) A, v =
      457.48(17) A(3), z = 1. Both germanates keep the same topological novel inorganic
      framework, which is assembled from Ge4(OH)4 cubane and chiral intertwined Ge-O
      double helices.

PMID- 16961363
TI  - Trigonal-bipyramidal geometry induced by an external water ligand in a sterically
      hindered iron salen complex, related to the active site of protocatechuate 3,4
      dioxygenase.
AB  - A unique distorted trigonal-bipyramidal geometry observed for the non-heme iron
      center in protocatechuate 3,4-dioxygenase (3,4-PCD) was carefully examined
      utilizing a sterically hindered iron salen complex, which well reproduces the
      endogenous His2Tyr2 donor set with water as an external ligand. X-ray crystal
      structures of a series of iron model complexes containing bis(3,5
      dimesitylsalicylidene)-1,2-dimesitylethylenediamine indicate that a distorted
      trigonal-bipyramidal geometry is achieved upon binding of water as an external
      ligand. The extent of a structural change of the iron center from a preferred
      square-pyramidal to a distorted trigonal-bipyramidal geometry varies with the
      external ligand that is bound in the order Cl << EtO < H2O, which is consistent
      with the spectrochemical series. The distortion in the model system is not due to
      steric repulsions but electronic interactions between the external ligand and the
      iron center, as evidenced from the X-ray crystal structures of another series of
      iron model complexes with a less-hindered bis(3-xylylsalicylidene)-1,2
      dimesitylethylenediamine ligand, as well as by density functional theory
      calculations. Further spectroscopic investigations indicate that a unique
      distorted trigonal-bipyramidal geometry is indeed maintained even in solution.
      The present model study provides a new viewpoint that a unique distorted trigonal
      bipyramidal iron site might not be preorganized by a 3,4-PCD protein but could be
      electronically induced upon the binding of an external hydroxide ligand to the
      iron(III) center. The structural change induced by the external water ligand is
      also discussed in relation to the reaction mechanism of 3,4-PCD.

PMID- 16961364
TI  - Tuning of inter- versus intrachain magnetic interactions in cyano-bridged
      Ni(II)/M(III) (M = Cr, Fe, Co) chain complexes.
AB  - The reaction of [M(CN)6]3- (M = Cr3+, Fe3+, Co3+) with the nickel(II) complex of
      2,4-diamino-1,3,5-triazin-6-yl-{3-(1,3,5,8,12-pentaazacyclotetradecane)}
      ([NiL]2+) in excess of ANO3 or ACl (A = Li+, Na+, K+, Rb+, Cs+, NH4+) leads to
      the cyano-bridged dinuclear assemblies A{[NiL][M(CN)6]}.xH2O (x = 2-5). X-ray
      structures of Li{[NiL][Cr(CN)6]}.5H2O, NH4{[NiL][Cr(CN)6]}.3.5H2O,
      K{[NiL][Cr(CN)6]}.4H2O, K{[NiL][Fe(CN)6]}.4H2O, Rb{[NiL][Fe(CN)6]}.3.5H2O, and
      Cs{[NiL][Fe(CN)6]}.3.5H2O, as well as the powder diffractometry of the entire
      Fe(III) series, are reported. The magnetic properties of the assemblies are
      dependent on the monocation A and discussed in detail. New efficient pathways for
      ferromagnetic exchange between Ni(II) and Fe(III) or Cr(III) are demonstrated.
      Field dependencies of the magnetization for the Fe(III) samples at low
      temperature and low magnetic field indicate a weak interchain antiferromagnetic
      coupling, which is switched to ferromagnetic coupling at increasing magnetic
      field (metamagnetic behavior). The interchain magnetic coupling can be tuned by
      the size of the A cations.

PMID- 16961365
TI  - EPR investigation and spectral simulations of iron-catecholate complexes and iron
      peptide models of marine adhesive cross-links.
AB  - Electron paramagnetic resonance (EPR) spectra are presented for iron complexes of
      catecholate, tironate, and a 3,4-dihydroxyphenylalanine (DOPA)-containing peptide
      of sequence Ac-Ala-DOPA-Thr-Pro-CONH2 ("AdopaTP"). This peptide was prepared to
      model potential metal-protein cross-links in the adhesive used by marine mussels,
      Mytilus edulis, for affixing themselves to surfaces. Spectra are shown for iron
      bound to each ligand in mono, bis, and tris coordination environments. For
      example, the catecholate complexes {Fe(cat)}, {Fe(cat)2}, and [Fe(cat)3]3- are
      provided. Detailed simulations are presented to describe the origin of spectra
      for the iron-catecholate and iron-peptide species, which show that the spectral
      features can be accounted for only with the inclusion of D- and E-strain. The
      spectroscopy of each compound is shown under both anaerobic and aerobic
      conditions. When exposed to air, the high-spin Fe3+ signal of [Fe(AdopaTP)3]3-
      decreases and an organic radical is formed. No other sample exhibited an
      appreciable radical signal. These data are discussed in light of the biomaterial
      synthesis carried out by marine mussels.

PMID- 16961366
TI  - Hybrid inorganic-metalorganic compounds containing copper(II)-monosubstituted
      Keggin polyanions and polymeric copper(I) complexes.
AB  - Four hybrid inorganic-metalorganic compounds containing copper(II)
      monosubstituted Keggin polyoxotungstates, K3[Cu(I)(4,4'
      bpy)]3[SiW11Cu(II)O39].11H2O (1), (paraquat)3[SiW11Cu(II)O39].6H2O (2; paraquat =
      N,N'-dimethyl-4,4'-bipyridinium), K3[Cu(I)(4,4'-bpy)]3[GeW11Cu(II)O39].11H2O (3),
      and Na2[Cu(I)(4,4'-bpy)]3[PW11Cu(II)O39(H2O)].4H2O (4), have been synthesized
      under autogenous pressure hydrothermal conditions and characterized by elemental
      analysis and infrared spectroscopy (FT-IR). The crystal structures of 1, 2, and 4
      have been established by single-crystal X-ray diffraction. The crystal packings
      are characterized by the presence of monodimensional extended entities: either
      the polymeric polyanion [SiW11CuO39]n(6n-) (2), the cationic [Cu(4,4'-bpy)]n(n+)
      chain (4), or both simultaneously as in compound 1, where the inorganic and
      metalorganic sublattices are mutually perpendicular. To asses the influence of
      packing in the copper(I) complex structural diversity found in compounds 1 and 4,
      a search in the CSD database has been performed and the resulting geometrical
      features have been analyzed and compared with experimental crystallographic data
      and DFT calculations.

PMID- 16961367
TI  - Crystal retro-engineering: structural impact on silver(I) complexes with changing
      complexity of tris(pyrazolyl)methane ligands.
AB  - The preparation and structures of seven new silver(I) complexes involving the
      parent tris(pyrazolyl)methane unit, [C(pz)(3)], as the donor set,
      {[C6H5CH2OCH2C(pz)3]Ag}(BF4), {[C6H5CH2OCH2C(pz)3]2Ag3}(CF3SO3)3,
      {[HOCH2C(pz)3]Ag}(BF4), {[HOCH2C(pz)3]Ag}(CF3SO3), {[HC(pz)3]2Ag2(CH3CN)}(BF4)2,
      {[HC(pz)3]Ag}(PF6), and {[HC(pz)3]Ag}(CF3SO3), are reported. This project is
      based on a retro-design of our multitopic C6H(6-n)[CH2OCH2C(pz)3]n (pz =
      pyrazolyl ring, n = 2, 3, 4, and 6) family of ligands in such a way that each new
      ligand has one fewer organizational feature. The kappa2-kappa1 bonding mode of
      the [C(pz)3] units to two silvers, also observed with the multitopic ligands, is
      the dominant structural feature in all cases. Changing the counterion has
      important effects on the local structures and on crystal packing. When these
      structures are compared to similar ones based on the multitopic C6H(6
      n)[CH2OCH2C(pz)3]n ligands, it has been shown that the presence of the rigid
      parts (central arene core and the [C(pz)3] units) are important in order to
      observe highly organized supramolecular structures. The presence of the flexible
      ether linkage is also crucial, allowing all noncovalent forces to manifest
      themselves in a cumulative and complementary manner.

PMID- 16961368
TI  - Gold(I) and silver(I) mixed-metal trinuclear complexes: dimeric products from the
      reaction of gold(I) carbeniates or benzylimidazolates with silver(I) 3,5
      diphenylpyrazolate.
AB  - Trinuclear mixed-metal gold-silver compounds are obtained by the reaction of
      gold(I) carbeniate [Au(mu-C(OEt)=NC6H4-p-CH3)]3, TR(carb), or gold(I) imidazolate
      [Au-mu-C,N-1-benzyl-2-imidazolate]3, TR(bzim), with silver(I) pyrazolate [Ag(mu
      3,5-Ph2pz)]3. The crystalline products are mixed-ligand, mixed-metal dimeric
      products [Au(carb)Ag2(mu-3,5-Ph2pz)2], [Au2(carb)2Ag(mu-3,5-Ph2pz)].CH2Cl2,
      [Au(bzim)2Ag2(mu-3,5-Ph2pz)], and [Au2(bzim)2Ag(mu-3,5-Ph2pz)]. They have been
      characterized by elemental analysis and 1H NMR and mass spectrometry. The X-ray
      structure of [Au(carb)Ag2(mu-3,5-Ph2pz)2] shows it to be a dimer with two Ag...Au
      contacts between the trinuclear units of 3.083(2) and 3.310(2) A and with average
      intramolecular Ag...Ag and Au...Ag distances of approximately 3.3 and 3.2 A,
      respectively. The structure of [Au2(carb)2Ag(mu-3,5-Ph2pz)].CH2Cl2 is a dimer
      with one intermolecular Au...Au attraction of 3.3354(10) A and a short Ag...Au
      distance of approximately 3.42 A and intramolecular Ag...Au and Au...Au contacts
      of approximately 3.2 and approximately 3.3 A, respectively. Packing diagrams of
      both complexes show that the dimeric units are independent, similar to their
      parent molecules. The dimers of trinuclear [Au(carb)Ag2(mu-3,5-Ph2pz)2] and
      [Au2(carb)2Ag(mu-3,5-Ph2pz)].CH2Cl2 crystallize in the triclinic space group P (Z
      = 2), a = 9.688(3) A, b = 15.542(4) A, c = 23.689(6) A, alpha = 82.560(5) degrees
      , beta = 87.887(6) degrees , gamma = 78.060(5) degrees , and the orthorhombic
      space group Pca2(1) (Z = 4), a = 29.644(4) A, b = 7.4582(10) A, c = 30.473(4) A,
      respectively. The structure of [Au(bzim)Ag2(mu-3,5-Ph2pz)2] is a dimer with two
      metallophilic Ag...Au interactions of 3.14 A. The complex crystallizes in the
      monoclinic space group C2/c (Z = 4), a = 26.368(5) A, b = 15.672(3) A, c =
      17.010(3) A, beta = 102.206(3) degrees .

PMID- 16961369
TI  - 2-Aminopyrrolines: new chiral amidinate ligands with a rigid well-defined
      molecular structure and their coordination to Ti(IV).
AB  - The use of an amino-oxazolinate (NN(ox) = kappa2-2,6-dimethylphenylamido-4(S)
      isopropyloxazoline) as a chiral analogue to amidinate ligands in the chemistry of
      titanium was found to lead to undesired side reactions. The reaction of 2,6
      dimethylphenylamido-4(S)-isopropyloxazoline with [Ti(NMe2)4] afforded the
      bis(amidinato) complex [Ti(NN(ox))2(NMe2)2] (2) which was thermally converted to
      the ring-opened decomposition products [Ti(NN(ox)){kappa3-N(2,6
      C6H3Me2)C(NMe2)NC(iPr)CH2O}(NMe2)] (3) and [Ti{kappa3-N(2,6-C6H3Me2)C(NMe2)
      NC(iPr)CH2O}2] (4). The NMR spectra of 4 recorded at low temperature displayed
      two sets of resonances corresponding to two symmetric isomers in a 2:5 ratio, the
      probable geometries of which were established by ONIOM (QM/MM) simulations. To
      suppress ring opening of the oxazolines, their oxygen atom was formally replaced
      by a CH2 group in the synthesis of a series of amino-pyrroline protioligands 2
      RN(H)(5-C4H5NR') (HN(R)N(R')). Their reaction with [Ti(NMe2)4] gave the thermally
      stable complexes [Ti(N(R)N(R'))2(NMe2)2], of which three derivatives were
      characterized by X-ray diffraction. They are stereochemically dynamic and undergo
      reversible ligand rearrangements in solution, for which the activation parameters
      were determined by variable-temperature (1)H NMR spectroscopy.

PMID- 16961370
TI  - Influence of solvent and weak C-H...O contacts in the self-assembled [Pt2M4{CC(3
      OMe)C6H4}8] (M = Cu, Ag) clusters and their role in the luminescence behavior.
AB  - New alkynyl complexes [Pt2M4{CC(3-OMe)C6H4}8] (M = Ag 1, Cu 2) have been
      synthesized and their structures and properties compared to those of related
      [Pt2M4(CCPh)8] compounds. For the Pt-Ag derivatives, the X-ray structures of the
      discrete yellow solvate monomer, [Pt2Ag4{CC(3-OMe)C6H4}8].2THF ([1.2THF]), and
      the dark garnet unsolvated polymeric form, [Pt2Ag4{CC(3-OMe)C6H4}8](infinity)
      ([1](infinity)), are presented. The yellow form ([1.2THF]) exhibits a distorted
      octahedral geometry of the metal centers with the platinum atoms mutually trans
      and the four silver atoms in the equatorial plane. Pairs of Ag atoms are weakly
      bridged by THF molecules [mu-Ag2...O(THF)]. The garnet form ([1](infinity)) has
      an unprecedented infinite stacked chain of octahedral clusters linked by short
      Pt...Pt bonds (3.1458(8) A). In both forms, different types of weak C-H...O (OMe)
      hydrogen bonds are observed. For comparative purposes, we have also provided the
      crystal structures of the yellow monomer form, [Pt2Ag4-(CCPh)8].CHCl3, and the
      red dimer form, [Pt2Ag4(CCPh)8]2 (Pt-Pt 3.221(2) A). These clusters display
      intense photoluminescence in both solution and the solid state, at room
      temperature and 77 K. The emission observed for the yellow form [1.2THF] in the
      solid state is assigned to a 3MLM'CT [Pt(d)/pi(CCR) --> Pt(p(z))/Ag(sp)/pi(CCR)]
      state modified by Pt...Ag, Ag...Ag, and Ag...(THF) contacts. However, in the
      garnet form [1](infinity) and in 2, the emissions are related to the axial Pt-Pt
      bonds and are assigned as phosphorescence from a metal-metal-to-ligand charge
      transfer (3MMLCT) excited state ([1](infinity)), or an admixture of a metal-metal
      (Pt-Pt) centered 3(dsigmap(z)sigma) and 3MMLCT excited state (2). For 1, a
      remarkable quenching and a shift to higher energies in the emission is observed
      on changing from CH2Cl2 to THF, and for both 1 and 2, the emission spectra at 77
      K varies with the concentration, showing their tendency to stack even in glass.

PMID- 16961371
TI  - Substituent effects in five oxo-centered trinuclear rhodium(III) clusters.
AB  - We here report the rates of water substitution by methanol-d(4) for four new oxo
      centered trinuclear rhodium(III) clusters with different carboxylate-bridging
      ligands, [Rh3(mu3-O)(mu-O2CR)6(OH2)3]+ (R = CH2CH3, CH2CH2Cl, CH2Cl, and CHCl2),
      and [Rh3(mu3-O)(mu-O2CCH3)6(OH2)3]+. By varying the R group alkyl chain, water
      substitution rates were found to span almost 3 orders of magnitude (k(298K) = 1.2
      x 10(-2)-2.3 x 10(-5) s(-1)) and reflect the following trend R = CH2CH3 > CH3 >
      CH2CH2Cl > CH(2)Cl > CHCl2. Activation parameters for substitution point toward a
      dissociative activation pathway (DeltaH = 99-115 kJ mol(-1); DeltaS = 48-52 J
      mol(-1) K(-1)), indicating that there is little association with the incoming
      methanol molecule during the formation of the transition-state complex. Because
      the mechanism for substitution in all five trimers has a considerable
      dissociative character, substitution rates are likely very similar to water
      exchange rates. These data suggest that the kinetic reactivity of the ligated
      waters is heavily influenced by the inductive ability of the aliphatic
      substituents, but yet the mechanism of substitution remains virtually unchanged.
      Structural data are also reported for the four new rhodium(III) trimer salts as
      well as 103Rh NMR spectra. We find that 103Rh NMR chemical shifts span more than
      200 ppm and mirror the same reactivity trend found for the rates of water
      substitution (103Rh delta (9406-9620 ppm): R = CH2CH3 < CH3 < CH2CH2Cl < CH2Cl <
      CHCl2). Taken together, these data suggest a means for estimating water exchange
      rates for other oxo-centered rhodium(III) trimers from chemical shift data alone.

PMID- 16961372
TI  - Lanthanide triple-stranded helicates: controlling the yield of the
      heterobimetallic species.
AB  - Two unsymmetrical ditopic hexadentate ligands designed for the simultaneous
      recognition of two different trivalent lanthanide ions have been synthesized,
      L(AB2) and L(AB3), where A represents a tridentate benzimidazole-pyridine
      benzimidazole coordination unit, B2 a diethylamine-substituted benzimidazole
      pyridine-carboxamide one, and B3 a chlorine-substituted benzimidazole-pyridine
      carboxamide moiety. Under stoichiometric 2:3 (Ln/L) conditions, these ligands
      self-assemble with lanthanide ions to yield triple-stranded bimetallic helicates.
      The crystal structures of four helicates with L(AB3) of composition
      [LnLn'(L(AB3))3](ClO4)6.solv (CeCe, PrPr, PrLu, NdLu) show the metal ions
      embedded into a helical structure with a pitch of about 13.2-13.4 A. The metal
      ions lie at a distance of 9.1-9.2 A and are nine-coordinated by the three ligand
      strands, which are oriented in a HHH (head-head-head) fashion, where all ligand
      strands are oriented in the same direction. In the presence of a pair of
      different lanthanide ions in acetonitrile solution, the ligand L(AB3) shows
      selectivity and gives high yields of heterobimetallic complexes. L(AB2) displays
      less selectivity, and this is shown to be directly related to the tendency of
      this ligand to form high yields of HHT (head-head-tail) isomer. A fine-tuning of
      the HHH left arrow over right arrow HHT equilibrium and of the selectivity for
      heteropairs of Ln(III) ions is therefore at hand.

PMID- 16961373
TI  - Polyester-based carborane-containing dendrons.
AB  - New carborane-containing dendrons based on a 2,2-bis(hydroxymethyl)propanoic acid
      scaffold have been prepared for applications in boron neutron capture therapy. A
      generation-2 carborane-containing dendron carrying 40 boron atoms was the highest
      generation synthetically available due to the steric crowding. The structure of
      this dendron has been simulated by molecular dynamics. A 10-carbon linker
      carrying a carboxylic group has been installed at the focal point of the dendron
      to distance the attachment point from the sterically hindered core.

PMID- 16961374
TI  - Synthesis, crystal structures, and magnetic properties of cyano-bridged
      honeycomblike layers M(V)-Cu(II) (M = Mo, W) chelated by a macrocyclic ligand.
AB  - Two cyano-bridged Cu(II)-M(V) [M = Mo (2), W (3)] complexes formed by self
      assembly of octacyanometalates [M(CN)8]3- (M = Mo, W) with a new molecular
      precursor [Cu(L2)]2+ (1) (L2 = a macrocyclic ligand) in a 2:3 ratio have been
      investigated in terms of structures and magnetic behaviors. The M2Cu3 repeating
      unit of both bimetallic compounds is extended to a two-dimensional honeycomblike
      layered structure. The pendant ethyl groups on L2 noticeably influence the
      structural parameters around the Cu center. Compared with the system composed of
      a macrocycle without a side group, Cu-N(ax) (ax = axial) distances become shorter
      and the Cu-N(ax)-C(ax) angles are more bent for 2 and 3. The magnetic data denote
      that the Cu(II) and M(V) spins undergo explicit ferromagnetic interactions via CN
      bridges. From a structural and magnetic point of view, given that the Cu-N(ax)
      bond length in the tetragonally distorted octahedral Cu(II) environment is long
      enough, the overall ferromagnetic character remains despite the variation of Cu
      N(ax)-C(ax) angle in this system.

PMID- 16961375
TI  - Iron complexes of N-confused pyriporphyrin: NMR studies.
AB  - Insertion of iron(II) into 6,11,16,21-tetraaryl-3-aza-m-benziporphyrin (N
      confused pyriporphyrin, (PyPH)H) yielded the high-spin iron(II) complex,
      (PyPH)Fe(II)Br. The coordination of iron(II) to the perimeter nitrogen atom of
      (PyPH)Fe(II)Br resulted in the formation of the diiron species. Oxidation and
      oxygenation of (PyPH)Fe(II)Br were followed by 1H NMR spectroscopy. The addition
      of Br2 to the solution of (PyPH)Fe(II)Br in the absence of dioxygen results in a
      one-electron oxidation yielding the high-spin iron(III) N-confused pyriporphyrin
      [(PyPH)Fe(III)Br]+ which preserves the side-on interaction between the inverted
      pyridine ring and metal ion. The reaction of (PyPH)Fe(II)Br with dioxygen ends up
      with the formation of a five-coordinate species (PyPO)Fe(III)Br] ((PyPOH)H = 3
      aza-22-hydroxy-m-benziporphyrin, PyPO = the corresponding dianion) which is
      formed by oxygenation at the C(22) position. Coordination of a metal ion by 3-aza
      22-hydroxy-benziporphyrin imposes a steric constraint on the geometry of the
      ligand. The halide ligand of (PyPO)Fe(III)Br coordinates on one of the two
      inequivalent faces of the macrocycle, leading to two distinct species: syn and
      anti. The (1)H NMR spectra of paramagnetic iron(II) and iron(III) N-confused
      pyriporphyrin complexes have been examined. The characteristic patterns of
      pyrrole and pyridine resonances have been found to be diagnostic of the ground
      electronic state of iron and the donor nature of the C(22)H and N(3) centers. The
      enormous downfield H(22) paramagnetic shift, determined for the iron(II) N
      confused pyriporphyrin, provides a distinct resonance in a peculiar spectroscopic
      window (350-800 ppm) for a series of axial ligands which can be considered as a
      diagnostic sign of an agostic Fe(II)...{C(22)-H} interaction. Coordination of the
      pyridine moiety via the perimeter N(3) atom is reflected unambiguously by the
      H(2/4) resonance at 201 ppm.

PMID- 16961376
TI  - Synthesis and characterization of novel fluorophosphazene-derived
      cobaltacyclopentadienyl metallacycles: reagents for assembly of aryl-bridged
      fluorophosphazenes.
AB  - Reaction of (beta-phenylethynyl)pentafluorocyclotriphosphazene, F5P3N3C identical
      with CPh, with in situ generated eta5-(MeOC(O)C5H4)Co(PPh3)2 resulted in the
      formation of two isomers of cobaltacyclopentadienylmetallacycles, (eta(5)
      carbomethoxycyclopentadienyl)(triphenylphosphine)-2,5
      bis(pentafluorocyclotriphosphazenyl)-3,4-diphenyl cobaltacyclopentadiene (1) and
      (eta5-carbomethoxycyclopentadienyl)(triphenylphosphine)-2,4
      bis(pentafluorocyclotriphosphazenyl)-3,5-diphenyl cobaltacyclopentadiene (2),
      along with the sandwich compound [eta5-carbomethoxycyclopentadienyl]-[eta4-1,3
      bis(pentafluorocyclotriphosphazenyl)-2,4-diphenylcyclobutadiene]cobalt (3).
      Formation of cobaltacyclopentadienylmetallacycles or cyclobutadienylmetallocene
      having two fluorophosphazene units on vicinal carbon atoms of the rings was not
      observed in this reaction. Reaction of 1 with diphenylacetylene resulted in the
      formation of a novel aryl-bridged fluorophosphazene, 1,4
      bis(pentafluorocyclotriphosphazenyl)-2,3,5,6-tetraphenyl benzene (4), and the
      conversion of cobaltametallacycle to the sandwich compound, [eta5
      (MeOC(O)C5H4]Co(eta4-C4Ph4) (5). Reaction of 1 with phenylacetylene resulted in
      the formation of aryl-bridged fluorophosphazene, 1,4-bis(pentafluorophosphazenyl)
      2,3,5,-triphenyl benzene (6). New compounds 1-4 were structurally characterized.
      In compound 1, the two fluorophosphazene units were oriented in gauche form with
      respect to each other. However, in compounds 2 and 3, they were eclipsed to each
      other, and in compound 4, they were oriented anti to each other.

PMID- 16961377
TI  - 195Pt NMR study of the speciation and preferential extraction of Pt(IV)-mixed
      halide complexes by diethylenetriamine-modified silica-based anion exchangers.
AB  - A detailed 195Pt NMR study of the distribution of Pt(IV) complex species
      resulting from the aquation of H2PtCl6, H2PtBr6, and mixtures of H2PtCl6/H2PtBr6
      in water/dilute HClO4 has been carried out to obtain an understanding of the
      speciation in these solutions as relevant to the recovery of Pt(IV) complexes
      from process solutions. A species distribution plot of the [PtCl6]2-,
      [PtCl5(H2O)]-, and [PtCl4(H2O)2] shows that in equilibrated, relatively
      concentrated H2PtCl6 solutions ([Pt]t > 0.12 M), the [PtCl4(H2O)2] species is
      below the 195Pt NMR detection limit; for [Pt]t concentrations < 0.1 M, the
      relative concentrations of the [PtCl5(H2O)]- and [PtCl4(H2O)2] species increase
      significantly, as a result of relatively rapid aquation of the [PtCl6]2- and
      [PtCl5(H2O)]- complexes under these conditions. From this (195)Pt NMR data the
      aquation constants of [PtCl6]2- and [PtBr6]2- of log K6 approximately 1.75 +/-
      0.05 and log K6 approximately 2.71 +/- 0.15, respectively, have been determined
      at 30 degrees C. In mixtures of H2PtCl6/H2PtBr6 in water, a number of previously
      unidentified aquated complexes of the general formula [PtCl(5-n)Br(n)(H2O)]- (n =
      0-5) could be identified, including the possible geometrical isomers of these
      complexes. These 195Pt NMR assignments were confirmed by remarkably systematic,
      linear relationships between the 195Pt chemical shift increments induced by
      substitution of Cl- ions by n Br- ions in [PtCl(6-n)Br(n)]2- and [PtCl(5
      n)Br(n)(H2O)]- complexes. Preferential extraction of the [PtX6]2- (X = Cl, Br, or
      a mixture of the two halides) species over their corresponding aquated
      [PtX5(H2O)]- counterparts by silica-based diethylenetriamine anion exchangers
      could be demonstrated by means of 195Pt NMR spectroscopy.

PMID- 16961378
TI  - Gas-phase reactions of atomic lanthanide cations with sulfur hexafluoride:
      periodicity in reactivity.
AB  - Room-temperature reactions of sulfur hexafluoride (SF6) have been surveyed
      systematically with atomic lanthanide cations (Ln+, excluding Pm+) in the gas
      phase, using an inductively coupled plasma/selected-ion flow tube (ICP/SIFT)
      tandem mass spectrometer. Rate coefficients and product distributions were
      measured in helium at a pressure of 0.35 Torr and temperature of 295 K. All the
      Ln+ cations were observed to react efficiently (k/kc > 0.24) and predominantly by
      single and multiple F atom and fluoride abstraction to produce both LnFn+ and
      SFn+(where n = 1, 2, 3). The observed periodic trend in reaction efficiency along
      the lanthanide row matches the periodic trend in the electron-promotion energy of
      the Ln+ cation. A remarkable Arrhenius-like correlation is observed for the
      dependence of reactivity on promotion energy: the early and late lanthanide
      cations exhibit effective temperatures of 45 500 and 14 000 K, respectively. SFn+
      product ions are observed to be unreactive with SF6, whereas up to two molecules
      of SF6 have been observed to add to LnFn+ product ions under the experimental
      operating conditions of the ICP/SIFT tandem mass spectrometer.

PMID- 16961379
TI  - Prediction of second-order optical nonlinearity of trisorganotin-substituted beta
      Keggin polyoxotungstate.
AB  - The dipole polarizabilities, second-order polarizabilities, and origin of second
      order nonlinear optical (NLO) properties of trisorganotin-substituted beta-Keggin
      polyoxotungstate [XW9O37(SnR)3](11-n)- (X = P, Si, Ge, R = Ph; X = Si, R = PhNO2,
      PhCCPh) have been investigated by using time-dependent density functional
      response theory. This class of organic-inorganic hybrid complexes possesses a
      remarkably large molecular second-order NLO response, especially for
      [SiW9O37(SnPhCCPh)3]7- (system 5) with the static second-order polarizability
      (beta(vec)) computed to be 1569.66 x 10(-30) esu. Thus, these complexes have the
      possibility to be excellent second-order nonlinear optical materials. Analysis of
      the major contributions to the beta(vec) value suggests that the charge transfer
      from the heteropolyanion to the organic segment along the z-axis plays the key
      role in the NLO response of [XW9O37(SnR)3](11-n)-. The computed beta(vec) values
      increase as a heavy central heteroatom changes in the order Ge > Si > P.
      Furthermore, nitro substitution on the aryl segment and the lengthening of
      organostannic pi-conjugation are more important in enhancing the optical
      nonlinearity, especially for the latter factor. The present investigation
      provides important insight into the origin of the NLO properties of trisorganotin
      substituted heteropolyoxotungstate.

PMID- 16961380
TI  - Nitrite impurities are responsible for the reaction observed between vitamin B12
      and nitric oxide in acidic aqueous solution.
AB  - The reaction between aquacobalamin, Cbl(H2O), and NO was studied at low pH. As
      previously reported, the final product of the reaction is the same as that
      obtained in the reaction of NO and reduced Cbl(H2O), viz. Cbl(NO-). Nevertheless,
      this reductive nitrosylation is preceded by a faster reaction (accompanied by
      small absorbance changes) that depends on the HNO2 concentration but not on the
      NO concentration. Kinetic and UV-vis spectroscopic data show that Cbl(NO2-) is
      generated during this reaction. Spectroscopic data show that the
      dimethylbenzimidazole group trans to the NO2- ligand is protonated and partially
      dechelated at pH 1, by which a reaction with NO is induced. DFT calculations were
      performed to compare the ability of NO and NO2- to bind to cobalamin and their
      influence on the stability of the dimethylbenzimidazole group. The reductive
      nitrosylation reaction shows a quadratic dependence on the HNO2 concentration and
      an inverse dependence on the NO concentration. It also strongly depends on pH and
      is no longer observed at pH > 4. On the basis of earlier work performed on a
      series of Co(III) porphyrins, a mechanism is proposed that can quantitatively
      account for the HNO2 and NO dependencies. The reductive nitrosylation reaction is
      practically dominated by a back reaction, i.e., the reaction between Cbl(NO-) and
      HNO2, which accounts for the strange NO and HNO2 concentration dependencies
      observed.

PMID- 16961381
TI  - Electronic structure of mononuclear bis(1,2-diaryl-1,2-ethylenedithiolato)iron
      complexes containing a fifth cyanide or phosphite ligand: a combined experimental
      and computational study.
AB  - A series of mononuclear square-based pyramidal complexes of iron containing two
      1,2-diaryl-ethylene-1,2-dithiolate ligands in various oxidation levels has been
      synthesized. The reaction of the dinuclear species [Fe(III)2(1L*)2(1L)2]0, where
      (1L)2- is the closed shell di-(4-tert-butylphenyl)-1,2-ethylenedithiolate dianion
      and (1L*)1- is its one-electron-oxidized pi-radical monoanion, with [N(n-Bu)4]CN
      in toluene yields dark green crystals of mononuclear [N(n-Bu)4][Fe(II)(1L*)2(CN)]
      (1). The oxidation of 1 with ferrocenium hexafluorophosphate yields blue
      [Fe(III)(1L*)2(CN)] (1ox), and analogously, a reduction with [Cp2Co] yields
      [Cp2Co][N(n-Bu)4][Fe(II)(1L*)(1L)(CN)] (1red); oxidation of the neutral dimer
      with iodine gives [Fe(III)(1L*)2I] (2). The dimer reacts with the phosphite
      P(OCH3)3 to yield [Fe(II)(1L*)2{P(OCH3)3}] (3), and [Fe(III)2(3L*)2(3L)2] reacts
      with P(OC6H5)3 to give [Fe(II)(3L*)2{P(OC6H5)3}] (4), where (3L)2- represents 1,2
      diphenyl-1,2-ethylenedithiolate(2-). Both 3 and 4 were electrochemically one
      electron oxidized to the monocations 3ox and 4ox and reduced to the monoanions
      3red and 4red. The structures of 1 and 4 have been determined by X-ray
      crystallography. All compounds have been studied by magnetic susceptibility
      measurements, X-band EPR, UV-vis, IR, and Mossbauer spectroscopies. The following
      five-coordinate chromophores have been identified: (a) [Fe(III)(L*)2X]n, X = CN-,
      I- (n = 0) (1ox, 2); X = P(OR)3 (n = 1+) )3ox, 4ox) with St = 1/2, SFe = 3/2; (b)
      [Fe(II)(L*)2X]n, X = CN-, (n = 1-) (1); X = P(OR)3 (n = 0) (3, 4) with St = SFe =
      0; (c) [Fe(II)(L*)(L)X]n <--> [Fe(II)(L)(L*)X]n, X = CN- (n = 2-) (1red); X =
      P(OR)3 (n = 1-) (3red, 4red) with St = 1/2, SFe = 0 (or 1). Complex 1ox displays
      spin crossover behavior: St = 1/2 <--> St = 3/2 with intrinsic spin-state change
      SFe = 3/2 <--> SFe = 5/2. The electronic structures of 1 and 1(ox) have been
      established by density functional theoretical calculations: [Fe(II)(1L*)2(CN)]1-
      (SFe = 0, St = 0) and [Fe(III)(1L*)2(CN)]0 (SFe = 3/2, St = 1/2).

PMID- 16961382
TI  - Potentiometric titration of metal ions in ethanol.
AB  - The potentiometric titrations of Zn2+, Cu2+ and 12 Ln3+ metal ions were obtained
      in ethanol to determine the titration constants (defined as the at which the [
      OEt]/[Mx+]t ratios are 0.5, 1.5, and 2.5) and in two cases (La3+ and Zn2+) a
      complete speciation diagram. Several simple monobasic acids and aminium ions were
      also titrated to test the validity of experimental titration measurements and to
      establish new constants in this medium that will be useful for the preparation of
      buffers and standard solutions. The dependence of the titration constants on the
      concentration and type of metal ion and specific counterion effects is discussed.
      In selected cases, the titration profiles were analyzed using a commercially
      available fitting program to obtain information about the species present in
      solution, including La3+ for which a dimer model is proposed. The fitting
      provides the microscopic values for deprotonation of one to four metal-bound
      ethanol molecules. Kinetics for the La3+-catalyzed ethanolysis of paraoxon as a
      function of are presented and analyzed in terms of La3+ speciation as determined
      by the analysis of potentiometric titration curves. The stability constants for
      the formation of Zn2+ and Cu2+ complexes with 1,5,9-triazacyclododecane as
      determined by potentiometric titration are presented.

PMID- 16961383
TI  - Coordination chemistry of amine bis(phenolate) cobalt(II), nickel(II), and
      copper(II) complexes.
AB  - Cobalt(II), nickel(II), and copper(II) (1, 2, and 3) complexes of the dianionic
      form of the bis(phenolate) ligand N,N-bis(3,4-dimethyl-2-hydroxybenzyl)-N',N'
      dimethylethylenediamine (H2L) have been synthesized by electrochemical oxidation
      of the appropriate metal in an acetonitrile solution of the ligand. When copper
      is used as the anode, the addition of 1,10-phenanthroline to the electrolytic
      phase gave rise to a different compound [CuL]2.2CH3CN (4). The compounds
      [CoL]2.2CH3CN (1), [Ni2L2(H2O)].H2O (2), [CuL]2.3H2O (3), and [CuL]2.2CH3CN (4)
      were characterized by microanalysis, IR, electronic spectroscopy, FAB mass
      spectrometry, magnetic measurements and by single-crystal X-ray diffraction. The
      crystal structures show that the complexes have a dinuclear structure. In
      compounds 1, 3, and 4, two metal ions are coordinated by the two amine nitrogens
      and the two phenol oxygen atoms of a deprotonated pendant phenol ligand, with one
      phenolic oxygen atom from ligand acting as a bridge. In compounds 1 and 3, each
      metal center has a geometry that is closest to trigonal bipyramidal. Magnetic
      susceptibility data for both compounds show an antiferromagnetic coupling with 2J
      = -15 cm(-1) for the cobalt(II) complex and a strong antiferromagnetic coupling
      with 2J = -654 cm(-1) for the copper(II) complex. However, in 4 the geometry
      around the metal is closer to square pyramidal and the compound shows a lower
      antiferromagnetic coupling (2J = -90 cm(-1)) than in 3. The nickel atoms in the
      dimeric compound 2 are hexacoordinate. The NiN2O4 chromophore has a highly
      distorted octahedral geometry. In this structure, a dianionic ligand binds to one
      nickel through the two amine nitrogen atoms and the two oxygen atoms and to an
      adjacent nickel via one of these oxygen atoms. The nickel atoms are linked
      through a triple oxygen bridge involving two phenolic oxygens, each from a
      different ligand, and an oxygen atom from a water molecule. The two nickel ions
      in 2 are ferromagnetically coupled with 2J = 19.8 cm(-1).

PMID- 16961384
TI  - The solution structures and dynamics and the solid-state structures of
      substituted cyclopentadienyltitanium(IV) trifluorides.
AB  - Organotitanium fluorides (C5Me4R)TiF3 (R = H, Me, Et) sublimate with formation of
      crystalline dimers. From solution, we obtained crystals of dimers and tetramers.
      The tetramer [{(C5Me5)TiF3}4] irreversibly dissociates in the solid state to
      dimers (DeltaH = 8.33 kcal mol(-1)). The variable-temperature (1)H and (19)F NMR
      spectroscopy measurements of the toluene-d(8) solution of [{(C5Me5)TiF3}2]
      revealed at 202 K one monomeric, two dimeric (with C2h and Cs symmetry), two
      tetrameric (with D2 and C2v symmetry), and two trimeric (both C2 symmetry)
      molecules. With the increase in temperature and dilution of the solution, the
      composition of the solution shifts to the smaller molecules. The thermodynamic
      and activation parameters for the reversible dissociation of dimers to monomers
      in the solution are DeltaH = 9.2 kcal mol(-1), DeltaS = 24.2 cal mol(-1) K(-1),
      DeltaH(double dagger) = 12.2 kcal mol(-1), DeltaS(double dagger) = 9.7 cal mol(
      1) K(-1). The dissociation path with a weakly double-bridged transition-state
      dimer was proposed. The thermodynamic parameters for the reversible dissociation
      of the C2v tetramer to the dimers in solution are DeltaH = 7.9 kcal mol(-1) and
      DeltaS = 26.8 cal mol(-1) K(-1). From both tetramers, the D2 molecule is 0.34(5)
      kcal mol(-1) lower in enthalpy and 6.5(5) cal mol(-1) K(-1) lower in entropy than
      the C2v molecule. The structures of both trimers were proposed. The low
      temperature 19F NMR spectra of the CDCl3 solution of [{(C5Me5)TiF3}2] are
      consistent with equilibria of a monomer, two dimers (with C2h and Cs symmetry),
      and a trimer. The vapor pressure osmometric molecular mass determination of CDCl3
      solution of [{(C5Me5)TiF3}2] at 302 K is consistent with the equilibrium of the
      dimer and the monomer.

PMID- 16961385
TI  - Phosphine-mediated dehalogenation reactions of trichloro(N
      silyl)phosphoranimines.
AB  - The reaction of N-(trimethylsilyl)phosphoranimine Cl3P=NSiMe3 (1) with nBu3P or
      Ph3P yields the N-(dichlorophosphino)phosphoranimines nBu3P=NPCl2 (4a) or
      Ph3P=NPCl2 (4b), respectively. Detailed studies of this reaction indicate a
      mechanism that involves the reductive dechlorination of 1 by the tertiary
      phosphine to yield nBu3PCl2 (5a) or Ph3PCl2 (5b) with the apparent formation of
      the transient chlorophosphinimine ClP=NSiMe3 (6), followed by condensation of 5a
      or 5b with 1 to form 4a or 4b and Me3SiCl. Convincing evidence for the proposed
      mechanism was revealed by studies of the analogous reaction between the N
      (triphenylsilyl)phosphoranimine Cl3P=NSiPh3 (8) with nBu3P and Ph3P. These
      reactions quantitatively generated 5a and 5b and also allowed the correspondingly
      more stable chlorophosphinimine ClP=NSiPh3 (10) to be identified.

PMID- 16961386
TI  - Osmium(VII) fluorine compounds.
AB  - Of the four published osmium fluorine compounds in the oxidation state +7, OsO3F,
      OsO2F3, OsOF5, and OsF7, only one (OsOF5) is a real Os(VII) compound. OsO(3)F has
      obviously been OsO4. OsO2F3 in its two modifications is a mixed-valence
      Os(VI)/Os(VIII) compound, whereas a new compound Os2O3F7 is a mixed-valence
      OsV/Os(VIII) compound. The molecular structures of OsO3F, OsO2F3, and OsO3F2 are
      calculated. OsO3F2 seems to exist in two forms, with D3h and Cs symmetry. The
      original preparation of OsF7 could not be reproduced, only OsF6 has been
      obtained.

PMID- 16961388
TI  - KCaEr2CuS5: a new pentanary rare-earth layered chalcogenide without
      substitutional disorder.
AB  - A new pentanary rare-earth chalcogenide without substitutional disorder,
      KCaEr2CuS5, was obtained from reaction of the Er-Ca-Cu-S precursor with KBr flux
      by either a two-step flux method or a direct reaction of the mixture of the
      binary components (1Cu2S:2Er2S3:3CaS) with excess KBr as flux. KCaEr2CuS5
      crystallizes in the orthorhombic space group Cmcm (No. 63) with a = 3.9327(5) A,
      b = 13.410(2) A, c = 17.042(2) A, V = 898.8(3) A(3), Z = 4, R = 0.0632, and Rw =
      0.0627. The KCaEr2CuS5 structure consists of four different building units: ErS6
      octahedra, CaS6 octahedra, CuS4 tetrahedra, and KS6 trigonal prisms; it is
      characterized by [Er2CuS5]3- layers that are formed by the interconnection of
      double ErS6 octahedral chains with CuS4 tetrahedral chains in the a-c plane. K+
      and Ca2+ cations are located in the cavities defined by S2- anions between the
      [Er2CuS5]3- layers. KCaEr2CuS5 is a semiconductor with an estimated band gap of
      2.4 eV and shows a Curie-Weiss paramagnetic behavior in the 5-300 K range.

PMID- 16961387
TI  - Influence of the reaction conditions on the self-assembly of lead(II) 5
      sulfosalicylate coordination polymers with chelating amine ligands.
AB  - The synthesis and crystal structures of [Pb(Hssal)(2,2'-bipy)(DMF)]n (1),
      [Pb(Hssal)(2,2'-bipy)(H2O)]n (2), [Pb(Hssal)(phen)(DMF)]n (3), and
      [Pb3(ssal)2(phen)3]n (4) were reported, where Hssal2- and ssal3- are doubly and
      fully deprotonated 5-sulfosalicylates, 2,2'-bipy is 2,2'-bipyridine, and phen is
      1,10-phenanthroline. Compounds 1-4 were synthesized by the various reaction
      conditions, such as reaction temperature, molar ratio, and pH, and these
      structures are formed by infinite chains or layers where Pb(II) ions are linked
      by Hssal2- or ssal3- bridges. Compound 1, which has a ladderlike chain, was
      formed in DMF/H2O. Compound 2 with a H2O molecule coordinated to Pb(II) was
      prepared by a hydrothermal reaction. Compounds 3 and 4 were synthesized in a
      higher pH compared to compounds 1 and 2, containing the 2,2'-bipy ligand. In 1-3,
      5-sulfosalicylates are doubly deprotonated, whereas in 4, 5-sulfosalicylate is
      fully deprotonated. Coordination modes of Hssal2- and ssal3- ligands in 1-4 are
      novel and are first reported in this presentation. Although compounds 1 and 3
      have the same structural topology, their aromatic-aromatic interactions are
      significantly different. The coordination spheres of Pb(II) ions in 1 and 3 are
      holodirected, whereas in 2 and 4, they feature somewhat hemidirected properties
      with small holes or gaps. Compound 4 exhibits some interesting features that (1)
      there is not any solvent in the structure, (2) there are extensively aromatic
      aromatic stacking interactions among aromatic rings, and (3) there is also a weak
      interaction between Pb(II) atoms in the trinuclear motif.

PMID- 16961389
TI  - Prediction of pKa values of nido-carboranes by density functional theory methods.
AB  - A great parallel exists between metal complexes of cyclopentadienyl and arene
      ligands on one side and metal complexes of the nido derivatives of the
      icosahedral o-carborane clusters. With few exceptions, the metal complexation in
      the cluster can be viewed as the substitution of one or more bridging hydrogen
      atoms by the metal. Therefore, a necessary requirement for the complexation is
      the deprotonation of the nido cluster to generate a coordination site for that
      metal. The reaction to remove these protons, which most probably is one of the
      most commonly done processes in boron and metallaborane chemistry, is barely
      known, and no quantitative data are available on the magnitude of their pKa
      values. With the purpose of determining the acidity of nido-carboranes, a
      procedure to calculate the pKa values of nido boron clusters is presented in this
      paper for the first time. To this objective, some nido clusters have been
      selected and their geometry and NMR-spectroscopic properties have been studied,
      giving a good correlation between the theoretical and experimental data in both
      geometry distances and 11B NMR spectroscopy. Of notice is the result that proves
      that the singular carbon atom in the thermodynamic isomer of [C2B10H13]- is
      definitely part of the cluster and that its connection with the C2B3 face would
      be better defined by adding additional interactions with the two boron atoms
      nearest to the second cluster carbon. The pKa values of the nido species have
      been calculated by correlating experimental pK(a) values and calculated reaction
      Gibbs energies DeltaG(s). Some pKa values of importance are -4.6 and +13.5 for
      7,8-[C2B9H13] (1) and 7,8-[C2B9H12]- (2), respectively.

PMID- 16961390
TI  - 2,2'-Dipyridylketone (dpk) as ancillary acceptor and reporter ligand in complexes
      [(dpk)(Cl)Ru(mu-tppz)Ru(Cl)(dpk)]n+ where tppz = 2,3,5,6-tetrakis(2
      pyridyl)pyrazine.
AB  - The tppz-bridged diruthenium(II) complex [(dpk)(Cl)Ru(II)(mu
      tppz)Ru(II)(Cl)(dpk)](ClO4)2, [2](ClO4)2, and mononuclear
      [(dpk)(Cl)Ru(II)(tppz)](ClO4), [1](ClO4) [tppz = 2,3,5,6-tetrakis(2
      pyridyl)pyrazine, dpk = 2,2'-dipyridylketone], have been synthesized. The 260 mV
      separation between successive one-electron oxidation couples in [2]2+ translates
      to a relatively small comproportionation constant, Kc, of 2.5 x 10(4) for the
      intermediate. It is shown how electrochemical data (E(ox), E(red), Kc) reflect
      the donor/acceptor effects of ancillary ligands L in a series of systems
      [(L)ClRu(mu-tppz)RuCl(L)]n, particularly the competition between L and tppz for
      electron density from the metal. According to EPR (g1 = 2.470, g2 = 2.195, and g3
      = 1.873 at 4 K) the intermediate [2]3+ is a mixed-valent Ru(II)Ru(III) species
      which shows a rather narrow intervalence charge transfer (IVCT) band at 1800 nm
      (epsilon = 1500 M(-1) cm(-1)). The width at half-height (Deltanu(1/2)) of 700 cm(
      1) of the IVCT band is much smaller than the calculated value of 3584 cm(-1),
      obtained by using the Hush formula Deltanu(1/2) = (2310E(op))(1/2) (E(op) = 5556
      cm(-1), energy of the IVCT transition) which would be applicable to localized
      (Class II) mixed-valent Ru(II)Ru(III) systems. Valence delocalization in [2]3+ is
      supported by the uniform shift of the nu(C=O) band of the N,N'-coordinated dpk
      ligands from 1676 cm(-1) in the Ru(II)Ru(II) precursor to 1690 cm(-1) in the
      Ru(2.5)Ru(2.5) form, illustrating the use of the dpk acceptor to act as reporter
      ligand via the free but pi-conjugated organic carbonyl group. The apparent
      contradiction between the moderate value of Kc and the narrow IVCT band is being
      discussed considering "borderline" or "hybrid" "Class II-III" concepts of mixed
      valency, as well as coordination aspects, i.e., the bis-tridentate nature of the
      pi-acceptor bridging ligand. Altogether, the complex ions [1]+ and [2]2+ display
      four and five successive reduction processes, respectively, involving both tppz-
      and dpk-based unoccupied pi orbitals. The one-electron reduced form [2]+ has been
      assigned as a tppz*- radical-anion-containing species which exhibits a free
      radical-type EPR signal at 4K (g(parallel) = 2.002, g(perpendicular) = 1.994) and
      one moderately intense ligand-based low-energy band at 965 nm (epsilon = 1100 M(
      1) cm(-1)).

PMID- 16961391
TI  - Distinct water-exchange mechanisms for trinuclear transition-metal clusters.
AB  - Mechanisms for water exchange from the bioxo-capped M-M-bonded trinuclear
      clusters, [M3(mu3-O)2(mu-O2CCH3)6(OH2)3]2+ [M = Mo(IV) and W(IV)], were
      investigated using high-pressure 17O NMR and compared to our previous work on a
      similar Rh(III) trimer. Reaction rates decrease by more than a factor of 2 when
      pressure is increased from 6 to 250 MPa for the Mo(IV) trimer, while exchange
      rates increase by less than a factor of 1.2 (10-229 MPa) for the W(IV) trimer.
      From the pressure dependence of the reaction rate, activation volumes (DeltaV())
      were calculated to be DeltaV() = +8.0 (+/-0.4) cm(3) mol(-1) and DeltaV = -1.9
      (+/-0.2) cm(3) mol(-1) for the Mo(IV) cluster and W(IV) cluster, respectively,
      which is the largest difference ( approximately 10 cm(3) mol(-1)) in activation
      volumes for any pair of 4d-5d (and 3d-4d) transition metal species located within
      the same group of the periodic table. If we interpret these activation volumes in
      terms of Swaddle's semiempirical model, which he established for simple
      octahedral monomers (Associative (A) = DeltaV approximately -13; Interchange (I)
      = DeltaV approximately 0; or Dissociative (D) = DeltaV approximately +13), our
      results suggest that water exchange follows a dissociative-interchange (Id)
      mechanism for the Mo(IV) cluster and an associative-interchange (Ia) activation
      mode for the W(IV) trimer. These volumes exhibit a unique changeover in the water
      exchange mechanism despite considerable similarities in molecular structure and
      reactivity. This changeover could provide a standard for computational
      simulations of ligand-exchange pathways in molecules that are more complicated
      than monomers.

PMID- 16961392
TI  - Condensation of [Si3O9]6- anions in the solid state to the dimeric
      cyclotrisilicate anion [Si6O17]10-.
AB  - The structure of the silicate Rb10[Si6O17] containing a novel dimeric
      cyclotrisilicate anion is reported. The compound is formed by the reaction of a
      mixture of SiO2 and Rb at temperatures above 700 degrees C. Systematic
      investigations by means of differential thermal analysis and temperature
      dependent powder X-ray diffraction experiments revealed that the new compound
      evolved from Rb6[Si3O9], which occurred as an intermediate product. Thus, the
      dimeric anion [Si6O17]10- is formed by condensation of the monomeric
      cyclotrisilicate [Si3O9]6-. For both silicates, [Si6O17]10- and [Si3O9]6-, the
      characteristic ring vibration modes were observed in the IR spectrum. The
      structure of Rb10[Si6O17] was solved and refined from single-crystal X-ray
      diffraction data in the orthorhombic space group Pbca (No. 61). Synthesis and
      structure determination of Rb10[Si6O17] bridge the gap to show that the recently
      reported structures of Rb14[Si4][Si6O17] and Rb14[Ge4][Si6O17] are indeed
      fascinating intergrowth structures of the stable oxide Rb10[Si6O17] and the Zintl
      phases RbSi (Rb4Si4) and RbGe (Rb4Ge4), respectively.

PMID- 16961393
TI  - Cu2{[18]ane-N6} complexes: structures, magnetism, and phosphate monoester
      binding.
AB  - A novel Cu(II)2 complex of the [18]ane-N6 macrocycle ([18]ane-N6 = 1,4,7,10,13,16
      hexaazacyclooctadecane) was prepared from the reaction between [18]ane-N6 and
      Cu(II) salts such as Cu(NO3)2 and Cu(OAc)2. A structural study of the complex
      derived from Cu(OAc)2 (1) revealed a Cu(II)2 core encircled by a [18]ane-N6
      ligand and two mu-O-OAc ligands. The facile replacement of mu-O-OAc by a
      phosphate monoester [PO3(OR)2-] yielded a number of bis(phosphate
      monoester)dicopper complexes with ROPO3(2-) as hydrogen phosphate (HPO4(2-), 3a),
      phenyl phosphate [PO3(OPh)2-, 3b], glycerol 2-phosphate [PO3(OCH(CH2OH)2)2-, 3c],
      alpha-d-gluocose phosphate [PO3(C6H11O6)2-, 3d], and dl-alpha-glycerol phosphate
      [PO3(OCH2CHOHCH2OH)2-, 3e]. Structural studies of compounds 3a-d confirmed both
      the retention of the Cu2{[18]ane-N6} core and a mu-O-PO3(OR) coordination mode.
      Displacement of acetate by a phosphate monoester in an aqueous solution was
      accompanied by a significant change in the visible absorption, which enables the
      establishment of relative association constants of PO3(OR)2- on the order of
      10(4) in the unbuffered solution and 10(3) in the buffered solution (HEPES).
      Measurement of the magnetic susceptibility of compound 3a over the temperature
      range of 5-300 K and subsequent modeling revealed a weak antiferromagnetic
      coupling (J = -1.1 cm(-1)) between two Cu(II) centers.

PMID- 16961394
TI  - Are the NF4+ cations in NF4BF4 really nontetrahedral?
AB  - The crystal structure of NF4BF4 has been reexamined. The low-temperature X-ray
      structure and solid-state 19F MAS NMR spectra are in agreement with the
      conclusions reached from the vibrational spectra, that solid NF4+ salts contain
      only tetrahedral NF4+ cations. The alleged observation of two kind of
      nontetrahedral NF4+ cations in several previous crystal structures is attributed
      to incorrectly solved structures and, possibly, problems caused by disorder or
      twinning. It is further evidence for the dangers of over-reliance on crystal
      structures. Flawed crystal structures can give rise to either bad or unwarranted
      theory.

PMID- 16961395
TI  - Comprehensive survey of combinatorial library synthesis: 2005.

PMID- 16961396
TI  - Carboxyl-functional ionic liquids as scavengers: case studies on benzyl chloride,
      amines, and methanesulfonyl chloride.

PMID- 16961397
TI  - A platform for both solid-phase peptide nucleic acid oligomer synthesis and
      subsequent in situ detection and quantification of nucleic acid sequences.

PMID- 16961398
TI  - Method for the parallel synthesis of alpha-methylene-gamma-lactones from a
      fluorous acrylate.

PMID- 16961399
TI  - Microwave-assisted solution-phase parallel synthesis of 2,4,6-trisubstituted
      pyrimidines.

PMID- 16961400
TI  - High-throughput ester hydrolysis with catch-and-release isolation of carboxylic
      acids.

PMID- 16961401
TI  - Incorporation of the Wang linker upon cleavage from polystyrene-based resin to
      form O-(4-hydroxy)benzyl derivatives.

PMID- 16961402
TI  - Microwave-assisted reaction of 2'-hydroxychalcones with hydrazides to synthesize
      flavanone hydrazone and 4,5-dihydropyrazole derivatives.

PMID- 16961403
TI  - Efficient Pd(0)-mediated microwave-assisted arylation of 2-substituted
      imidazo[1,2-a]pyrimidines.
AB  - A short and practical synthesis of 2,3-substituted imidazo[1,2-a]pyrimidines,
      based on microwave-assisted Heck-type arylation of 2-substituted imidazo[1,2
      a]pyrimidines, was developed. A 45-membered library of 2,3-substituted
      imidazo[1,2-a]pyrimidines was obtained with good yields and purities using this
      optimized protocol.

PMID- 16961404
TI  - Application of lean manufacturing concepts to drug discovery: rapid analogue
      library synthesis.
AB  - The application of parallel synthesis to lead optimization programs in drug
      discovery has been an ongoing challenge since the first reports of library
      synthesis. A number of approaches to the application of parallel array synthesis
      to lead optimization have been attempted over the years, ranging from widespread
      deployment by (and support of) individual medicinal chemists to centralization as
      a service by an expert core team. This manuscript describes our experience with
      the latter approach, which was undertaken as part of a larger initiative to
      optimize drug discovery. In particular, we highlight how concepts taken from the
      manufacturing sector can be applied to drug discovery and parallel synthesis to
      improve the timeliness and thus the impact of arrays on drug discovery.

PMID- 16961406
TI  - A combinatorial approach to the study of particle size effects on supported
      electrocatalysts: oxygen reduction on gold.
AB  - A novel high-throughput technique has been developed for the investigation of the
      influence of supported metal particle size and the support on electrocatalytic
      activity. Arrays with a gradation of catalyst particle sizes are fabricated in a
      physical vapor deposition system that also allows selection of the support
      material. Simultaneous electrochemical measurements at all electrodes in the
      array, together with determination of the actual particle size distribution on
      each of the electrodes by transmission electron microscopy (TEM), then allows
      rapid determination of the activity as a function of catalyst center size. The
      procedure is illustrated using data for the reduction of oxygen on gold
      nanoparticles supported on both substoichiometric titanium dioxide (TiO(x)()) and
      carbon and the conclusions are verified using voltammetry at rotating disk
      electrodes. Gold centers with diameters in the range 1.4-6.3 nm were investigated
      and it is demonstrated that, with both supports, the catalytic activity for
      oxygen reduction decays rapidly for particle sizes below 3.0 nm. This may be
      observed as a decrease in current at constant potential or an increase in the
      overpotential for oxygen reduction.

PMID- 16961405
TI  - Optimization of polymerization conditions of furan with aniline for variable
      conducting polymers.
AB  - A high-throughput multiparameter optimization of chemical oxidative
      polymerization conditions has been developed for a facile synthesis of furan
      homopolymers and furan/aniline copolymers using a combinatorial method. The
      polymerization yield, molecular structure, and properties of the polymers would
      be optimized against typical polymerization parameters, including oxidant
      species, medium species, temperature, oxidant/monomer ratio, monomer
      concentration, dopant concentration, and furan/aniline comonomer ratio. The
      electrical conductivity, lead ion adsorptivity, chemical resistance, and thermal
      behavior of the polymers were also elaborated. It is found that only a
      combination of FeCl(3) and nitromethane as oxidant and medium, respectively, is
      appropriate for the furan homopolymerization. The homopolymerization yield
      increases consistently with an increase in the monomer concentration from 0.05 to
      0.2 M and the FeCl(3)/furan molar ratio from 0.25 to 1.25. Although the as
      prepared polyfuran exhibits very low conductivity, down to 10(-11) S cm(-1), the
      HCl- and HClO(4)-doped polyfurans possess much higher conductivities of 9.2 x 10(
      8) and 2.38 x 10(-5) S cm(-1), respectively. In addition, the conductivity of the
      furan/aniline copolymer rises steadily with increasing aniline content, although
      the copolymerization yield shows a minimum at the furan/aniline molar ratio of
      60/40, which is evidence of the occurrence of a real copolymerization between the
      furan and aniline monomers. The difficulty of synthesizing conducting polyfuran
      could be overcome to some extent by the polymerization in an appropriate
      condition optimized in this study. Particularly, the difficulty of synthesizing
      poly(furan-co-aniline) having much higher conductivity than the polyfuran would
      be largely conquered by chemical oxidative copolymerization of furan with
      aniline.

PMID- 16961408
TI  - Synthesis of functionalized quinolines via Ugi and Pd-catalyzed intramolecular
      arylation reactions.
AB  - Two types of quinoline scaffolds were constructed in a combinatorial format via
      the Ugi four-component reaction (U-4CR) and Pd-catalyzed intramolecular arylation
      reaction. The scope of this two-step synthetic sequence was examined from
      commercially available and synthetically accessible starting materials.

PMID- 16961409
TI  - Development of a mass-directed preparative supercritical fluid chromatography
      purification system.
AB  - In this paper, we report the development of a mass-directed supercritical fluid
      chromatography (SFC) purification system. We have addressed issues on software
      compatibility, the interface between the preparative SFC and the mass
      spectrometer, and fraction collection. Good peak shape and signal were achieved
      in the mass spectrometry (MS) trace, allowing accurate peak detection and
      reliable fraction collection. Simple modifications on a commercially available
      fraction collector enabled fractionation at atmospheric pressure with high
      recovery. The SFC/MS purification system has been used in support of high
      throughput library purification and has been proven to be a valuable tool in
      complementing our reversed-phase high-performance liquid chromatograph (RP
      HPLC/MS)-based technology platform.

PMID- 16961407
TI  - Fluorous mixture synthesis of two libraries with hydantoin-, and
      benzodiazepinedione-fused heterocyclic scaffolds.
AB  - Diversity-oriented synthesis (DOS) and fluorous mixture synthesis (FMS) are two
      aspects of combinatorial chemistry. DOS generates library scaffolds with
      skeletal, substitution, and stereochemistry variations, whereas FMS is a highly
      efficient tool for library production. The combination of these two aspects in
      solution-phase synthesis of two novel heterocyclic compound libraries is
      presented in this paper. Mixtures of different fluorous amino acids undergo [3 +
      2] cycloadditions followed by postcondensation reactions. The mixtures are then
      demixed by fluorous HPLC. Fluorous tags are removed by cyclization to afford
      hydantoin- and benzodiazepinedione-fused heterocyclic compounds as individual,
      pure, and structurally defined molecules. The application of MS-directed HPLC
      purification and parallel four-channel LC/MS analysis further increases the
      efficiency of FMS.

PMID- 16961410
TI  - Part 1. modular approach to obtaining diverse tetrahydroquinoline-derived
      polycyclic skeletons for use in high-throughput generation of natural-product
      like chemical probes.
AB  - A practical synthesis of a tetrahydroaminoquinoline scaffold (12) was developed
      that used a stereocontrolled aza Michael as the key reaction. Three
      tetrahydroquinoline alkaloid-like, tricyclic derivatives 16, 18, and 19 with
      different medium to macrocyclic ring skeletons were obtained, using this scaffold
      as the starting material, in a modular manner. The macrocyclic compounds with an
      isolated olefin and an electron-deficient olefin were obtained by ring-closing
      metathesis approaches. Compounds 16 and 18 are unique and contain bridged 10- and
      12-membered functionalized rings. The NMR studies of these compounds revealed
      interesting information on the conformation of the bicyclic scaffolds that was
      dependent on the nature and the size of the macrocyclic rings. Finally, this
      modular methodology, using compound 21 anchored onto the solid support,
      successfully led to the generation of different macrocyclic derivatives, 23, 25,
      and 27 in solid-phase synthesis. The solid-phase synthesis approach outlined in
      this article has the potential to generate tetrahydroquinoline-based tricyclic
      compounds containing different medium to macrocyclic architectures.

PMID- 16961411
TI  - Part 2: building diverse natural-product-like architectures from a
      tetrahydroaminoquinoline scaffold. Modular solution- and solid-phase approaches
      for use in high-throughput generation of chemical probes.
AB  - The solution- and solid-phase synthesis to obtain several natural-product-like,
      tetrahydroquinoline-based, polycyclic derivatives were developed. In one
      approach, two derivatives (38 and 41) having an eight-membered unsaturated lactam
      were successfully obtained both in solution and on solid support.

PMID- 16961412
TI  - Part 3. a novel stereocontrolled, in situ, solution- and solid-phase, Aza Michael
      approach for high-throughput generation of tetrahydroaminoquinoline-derived
      natural-product-like architectures.
AB  - With the goal of rapidly accessing tetrahydroquinoline-based natural-product-like
      polycyclic architectures, herein, we report an unprecedented, in situ,
      stereocontrolled Aza Michael approach in solution and on the solid phase. The
      mild reaction conditions required to reach the desired target are highly
      attractive for the use of this method in library generation. To our knowledge,
      this approach has not been used before, and it opens a novel route leading to a
      wide variety of tetrahydroquinoline-derived bridged tricyclic derivatives.

PMID- 16961413
TI  - Diverse 2-carboxamide-3-amino-substituted quinoxalines: synthesis and reactivity
      investigation for library generation.
AB  - Described herein is the development of a robust synthetic route applicable to
      parallel synthesis of diverse 2-carboxamide-3-amino-substituted quinoxalines. In
      addition to the scope and limitations of the methods developed, a purification
      strategy employing solid-phase extraction (SPE) and application of the methods to
      a small parallel array of compounds are discussed.

PMID- 16961414
TI  - Synthesis of platinum(II) chiral tetraamine coordination complexes.
AB  - The individual and combinatorial syntheses of individual as well as a mixture
      based diversity of 195 112 platinum(II) coordination complexes of chiral
      tetraamines are described. The use of both solid-phase synthesis and solution
      phase follow-on approaches were found to best afford the title compounds.

PMID- 16961415
TI  - Parallel synthesis of diarylureas and their evaluation as inhibitors of insulin
      like growth factor receptor.
AB  - Diarylurea (DAU) compounds, particularly species composed of a heteroaryl ring
      system conjugated through a urea linkage to a substituted arene, were previously
      identified by the screening of a diverse chemical library to be active against
      the insulin growth factor receptor (IGF-1R). DAU compounds 4{a,b} were
      synthesized in parallel by the coupling of aryl amines 2{a} with aryl isocyanates
      3{b}. Preparative RP-HPLC purification was found necessary to remove an impurity
      5{b}, the symmetric urea resulting from the hydrolytic degradation of aryl
      isocyanates. Two libraries of DAU compounds were prepared to perform preliminary
      optimization of the two-ring systems for inhibitory activity against IGF-1R. In
      the first library, we explored a series of heteroaryl ring systems and found the
      4-aminoquinaldine ring system to be optimal among those evaluated. The second
      library fixed the 4-aminoquinaldine ring system and we evaluated a series of
      substituted arenes conjugated to it. Overall, eight compounds based on the 4
      aminoquinaldine heteroaryl system were found to have moderate activity against
      IGF-1R with IC(50) values better than 40 microM.

PMID- 16961416
TI  - Combinatorial approach to the study of particle size effects in electrocatalysis:
      synthesis of supported gold nanoparticles.
AB  - A high-throughput method for physical vapor deposition has been applied to the
      synthesis of libraries of supported gold particles on amorphous substoichiometric
      TiO(x)() and carbon supports. The TiO(x)() substrate stoichiometry can be varied
      or kept constant across a supporting sample, and subsequent deposition of
      particle sizes on supports are controlled through the nucleation and growth
      process. TEM measurements indicate nucleation and growth of Au particles takes
      place, with the smallest particles initially observed at 1.4 nm with a maximum
      density of 5.5 x 10(12) cm(-2) on titania, and 2.6 nm with concomitantly lower
      density on carbon. The 1.4-nm particles on titania exhibit a binding energy shift
      in the Au(4f) core level of 0.3 eV from bulk gold, and the shift is approximately
      0.1 eV by the time particles grow to a mean size of 2.5 nm. These shifts are
      associated with final state effects, and the supported gold particles are
      metallic and appear to be relatively stable in air. When combined with
      appropriate substrates and screening techniques, this method provides a highly
      controllable method for the high-throughput synthesis of model supported
      catalyst.

PMID- 16961418
TI  - Prevalence and consequences of the dual diagnosis of substance abuse and severe
      mental illness.
AB  - The co-occurrence of a severe mental illness and a substance use or abuse
      disorder is common in the United States as well as internationally and could be
      considered as more the expectation than the exception when assessing patients
      with serious mental illness. Substance use disorders can occur at any phase of
      the mental illness, perhaps even inducing psychosis. Causes of this comorbidity
      may include self-medication, genetic vulnerability, environment or lifestyle,
      underlying shared origins, and/or a common neural substrate. The consequences of
      dual diagnosis include poor medication compliance, physical comorbidities and
      poor health, poor self-care, increased suicide risk or aggression, increased
      sexual behavior, and possible incarceration. All of these factors contribute to a
      greater health burden, which reduces the health care system's capacity to
      adequately treat patients. Therefore, screening, assessment, and integrated
      treatment plans for dual diagnosis that can address both the addiction disorder
      and the mental illness are recommended in order to provide accurate treatment,
      after-care, and other health care to accommodate patients' social and vocational
      needs.

PMID- 16961419
TI  - Psychosocial interventions for the long-term management of patients with severe
      mental illness and co-occurring substance use disorder.
AB  - People with severe mental illness and co-occurring substance use disorders, also
      referred to as dual disorders, experience worse outcomes over the long term than
      people without co-occurring substance abuse. Integrated treatment of both
      disorders has been shown to be more effective than separate treatments offered in
      parallel or in sequence. The principles and strategies of integrated dual
      disorder treatment (IDDT) include integration of treatments for the mental
      illness and the addiction, use of strategies to engage people in treatment, use
      of pharmacologic and psychosocial interventions that are matched to the patient's
      stage of change, and use of a long-term perspective. The stages of change, the
      stages of treatment, and the psychosocial strategies used at each stage of
      treatment are outlined.

PMID- 16961420
TI  - Adolescent substance abuse and psychiatric comorbidities.
AB  - Substance use disorders have a serious impact on adolescents because these
      disorders have high prevalence rates and frequent associations with psychiatric
      disorders. Surveys of adolescent behaviors and substance use show that alcohol is
      the most common substance abused by adolescents. Despite the high rates of
      current alcohol use and binge drinking among adolescents, current diagnostic
      criteria are problematic. Adolescents may have a developing problem with
      substance dependence but not meet criteria for either substance abuse or
      dependence. At-risk adolescents, called "diagnostic orphans," may meet only 1 or
      2 criteria for alcohol dependence and no abuse criteria and therefore do not
      receive an alcohol use disorder diagnosis from the Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition, Text Revision. Adolescents with
      substance use disorders tend to have higher rates of comorbid psychiatric
      disorders and are more likely to report a history of trauma and physical and/or
      sexual abuse than adolescents without a substance use disorder. In addition,
      psychiatric disorders in adolescents often predate the substance use disorder.
      Once the substance use disorder develops, the psychiatric disorder may be further
      exacerbated.

PMID- 16961421
TI  - Management of comorbid bipolar disorder and substance abuse.
AB  - Bipolar disorder is a severe and often chronic disorder with lifetime prevalence
      rates of bipolar spectrum disorders of up to 6.5% in the general population.
      Patients with bipolar disorder frequently report co-occurring substance use
      disorders, and the rates of alcohol and other substance use disorders are
      significantly higher in persons with bipolar disorder than in the general
      population. The present review discusses why people with bipolar disorder use
      substances, provides an overview of the impact of alcohol and other substance use
      on the course of bipolar disorder, and outlines the treatment options currently
      available to patients with co-occurring bipolar disorder and substance abuse. Our
      aim is to summarize the existing data on the pharmacologic treatment options and
      to include the most recent published data whenever possible. Three randomized,
      placebo-controlled studies of dual-diagnosis patients treated with carbamazepine,
      lithium, and valproate are discussed. The results are generally positive and
      support the use of these agents in dual-diagnosis patients. Open-label studies
      are also presented, and the need for controlled data is outlined. The review also
      briefly discusses the psychotherapeutic approaches to patients with comorbid
      bipolar and substance use disorders.

PMID- 16961422
TI  - Treatment of schizophrenia and comorbid substance abuse: pharmacologic
      approaches.
AB  - Co-occurring substance use disorder is common among patients with schizophrenia,
      and its presence greatly worsens the course of schizophrenia. A number of
      theories have been introduced to explain the increased rate of substance use
      disorder in these patients. These theories include the notion that substance use
      could trigger psychotic symptoms in vulnerable individuals and the idea that the
      substances are used to self-medicate symptoms of schizophrenia. Our group and
      others have advanced a neurobiological hypothesis to explain this comorbidity
      that a mesocorticolimbic brain reward circuit underlies the substance use
      disorder in patients with schizophrenia. Treatment of substance use disorder in
      these patients is best done with integrated treatment programs that combine
      psychosocial interventions with pharmacotherapy. Recent data suggest that the
      atypical antipsychotic clozapine and perhaps other atypical agents may lessen
      substance use in patients with schizophrenia. My colleagues and I have proposed
      that clozapine's effect in these patients may be related to its ability to
      decrease the brain reward circuit dysfunction. Research is continuing on the use
      of atypical antipsychotics in patients with schizophrenia and comorbid substance
      abuse. The adjunctive use of naltrexone or other agents also may be helpful.
      Further research on the optimal pharmacologic approach to patients with dual
      diagnosis is needed.

PMID- 16961423
TI  - Introduction: new developments in the treatment of attention
      deficit/hyperactivity disorder.

PMID- 16961424
TI  - Fundamentals of attention-deficit/hyperactivity disorder: circuits and pathways.
AB  - Neuropsychological and imaging studies have shown that attention
      deficit/hyperactivity disorder (ADHD) is associated with alterations in
      prefrontal cortex (PFC) and its connections to striatum and cerebellum. Research
      in animals, in combination with observations of patients with cortical lesions,
      has shown that the PFC is critical for the regulation of behavior, attention, and
      affect using representational knowledge. The PFC is important for sustaining
      attention over a delay, inhibiting distraction, and dividing attention, while
      more posterior cortical areas are essential for perception and the allocation of
      attentional resources. The PFC in the right hemisphere is especially important
      for behavioral inhibition. Lesions to the PFC produce a profile of
      distractibility, forgetfulness, impulsivity, poor planning, and locomotor
      hyperactivity. The PFC is very sensitive to its neurochemical environment, and
      optimal levels of norepinephrine and dopamine are needed for proper PFC control
      of behavior and attention. Recent electrophysiologic studies in animals suggest
      that norepinephrine enhances "signals" through postsynaptic alpha2A-adrenoceptors
      in PFC, while dopamine decreases "noise" through modest levels of D1-receptor
      stimulation. Blockade of alpha2-receptors in the monkey PFC re-creates the
      symptoms of ADHD, resulting in impaired working memory, increased impulsivity,
      and locomotor hyperactivity. Genetic alterations in catecholamine pathways may
      contribute to dysregulation of PFC circuits in this disorder. Stimulant
      medications may have some of their therapeutic effects by increasing endogenous
      stimulation of alpha2A-adrenoceptors and dopamine D1-receptors in the PFC,
      optimizing PFC regulation of behavior and attention.

PMID- 16961425
TI  - Candidate gene studies of attention-deficit/hyperactivity disorder.
AB  - A growing body of behavioral and molecular genetics literature has indicated that
      the development of attention-deficit/hyperactivity disorder (ADHD) may be
      attributed to both genetic and environmental factors. Family, twin, and adoption
      studies provide compelling evidence that genes play a strong role in mediating
      susceptibility to ADHD. Molecular genetic studies suggest that the genetic
      architecture of ADHD is complex, while the handful of genome-wide scans conducted
      thus far is not conclusive. In contrast, the many candidate gene studies of ADHD
      have produced substantial evidence implicating several genes in the etiology of
      the disorder. For the 8 genes for which the same variant has been studied in 3 or
      more case-control or family-based studies, 7 show statistically significant
      evidence of association with ADHD based on pooled odds ratios across studies: the
      dopamine D4 receptor gene (DRD4), the dopamine D5 receptor gene (DRD5), the
      dopamine transporter gene (DAT), the dopamine beta-hydroxylase gene (DBH), the
      serotonin transporter gene (5-HTT), the serotonin receptor 1B gene (HTR1B), and
      the synaptosomal-associated protein 25 gene (SNAP25). Recent pharmacogenetic
      studies have correlated treatment nonresponse with particular gene markers, while
      preclinical studies have increased our understanding of gene expression paradigms
      and potential analogs for human trials. This literature review discusses the
      relevance and implications of genetic associations with ADHD for clinical
      practice and future research.

PMID- 16961426
TI  - Executive functions in attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: To examine the association between weaknesses in executive functions
      and attention-deficit/hyperactivity disorder (ADHD). METHOD: Empirical studies
      examining executive functions in ADHD samples were reviewed, with particular
      attention to results of recent meta-analyses. RESULTS: ADHD is associated with
      impaired performance on measures of response inhibition, working memory, and
      other aspects of executive functions, yet data also suggest significant
      neuropsychological variability within and across ADHD samples. CONCLUSION: ADHD
      may be best conceptualized as a neuropsychologically heterogeneous condition.
      More work is needed to characterize this heterogeneity and its clinical and
      pathophysiologic implications.

PMID- 16961427
TI  - ADHD and comorbidity in childhood.
AB  - In recent years, evidence has been accumulating regarding high levels of
      comorbidity between attention-deficit/hyperactivity disorder (ADHD) and a number
      of disorders, including mood and anxiety disorders and conduct disorder. Thus,
      ADHD is most likely a group of conditions, rather than a single homogeneous
      clinical entity, with potentially different etiologic and modifying risk factors
      and different outcomes. Follow-up studies of children with ADHD indicate that
      subgroups of subjects with ADHD and comorbid disorders have a poorer outcome as
      evidenced by significantly greater social, emotional, and psychological
      difficulties. Investigation of these issues should help to clarify the etiology,
      course, and outcome of ADHD.

PMID- 16961428
TI  - Mechanism of action of agents used in attention-deficit/hyperactivity disorder.
AB  - Several medications have been demonstrated effective in treating individuals with
      attention-deficit/hyperactivity disorder (ADHD). There appears to be some
      commonality in the physiologic mechanisms of action of these agents relevant to
      the treatment of ADHD. Either direct or indirect attenuation of dopamine and
      norepinephrine neurotransmission appears related to both the stimulant and
      nonstimulant medications efficacious in ADHD. However, important differences
      exist both between and within the specific classes of agents. Elucidating the
      various mechanisms of action of ADHD medications may lead to better choices in
      matching potential response to the characteristics (e.g., genotype) of
      individuals.

PMID- 16961429
TI  - Effectiveness outcomes in attention-deficit/hyperactivity disorder.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is common, chronic, and
      associated with significant functional impairment. It is highly treatable. It is
      therefore not only a major public health problem but also one that provides a
      unique opportunity in medicine to make a significant difference. This article
      will discuss the methodology needed to demonstrate empirically the impact of
      treatment on actual burden of illness in practice. Where efficacy studies
      demonstrate whether a treatment can work, effectiveness studies tell us whether
      they actually do work. Clinical trials exclude incompetent, non-compliant, and
      seriously comorbid patients, so that the information obtained from these trials
      tells us the most about the patients we see the least. Small differences in
      effect size in pivotal trials of efficacy have become a key variable for rating
      treatments as first line or second line, without consideration of effectiveness
      variables such as comorbidity, difficulty with appetite or sleep, patient
      preference, capacity for compliance, timing of functional impairment, and
      substance use. These effectiveness variables are less well studied, but critical
      to clinical decision making. In reality, fewer than 10% of our patients comply
      with and persist with treatment. To learn more about why patients are
      discontinuing treatment, we need to explore measures of effectiveness
      empirically. Effectiveness studies are also important to provide regulatory
      bodies with the data they need to balance the risk of treatment with the risk of
      failing to treat. Practical clinical trials and naturalistic follow-up studies
      will allow us to evaluate the true clinical impact of short-term efficacy trials.

PMID- 16961430
TI  - Cognitive-behavioral approaches to ADHD treatment in adulthood.
AB  - Attention-deficit/hyperactivity disorder (ADHD) in adolescence and adulthood is a
      chronic, distressing, and interfering neurobiologically based disorder that is
      primarily treated with medications. However, most individuals treated with
      medications continue to evidence at least some residual symptoms and functional
      impairments. These residual symptoms may be amenable to a structured, cognitive
      behavioral treatment approach. Recommendations for treatment of ADHD in
      adolescents and adults therefore call for psychosocial intervention concomitant
      with medications. This article is a review of the extant research on outcome
      studies of psychosocial interventions for adults with ADHD, including the
      successful randomized controlled trial of cognitive-behavioral therapy (CBT) my
      colleagues and I conducted. The article also includes a presentation of our model
      of treatment of residual ADHD in adulthood, which includes initiating CBT after
      medication stabilization, and an overview of the components of our specific CBT
      approach for residual ADHD that is geared toward adults and, potentially,
      adolescents.

PMID- 16961431
TI  - Primary care treatment of attention-deficit/hyperactivity disorder.
AB  - Primary care physicians should consider the role of families of patients with
      attention-deficit/ hyperactivity disorder (ADHD) not just in terms of their
      genetic relationship but also in terms of the role family can play in assisting
      in the treatment and management of the disorder. When first encountering a new
      case of ADHD, primary care physicians should confirm the diagnosis, identify
      comorbidities and other primary disorders, and develop a comprehensive assessment
      of the patient with ADHD that includes consideration of family-related
      influences. Management of multiple medical, mental health, and psychosocial
      problems over time will often be ineffective if ADHD is not adequately managed.
      The most effective management should be multimodal, with patients benefiting from
      caring professionals with special expertise in the treatment of ADHD as well as
      the primary care physician. Successful management of ADHD begins with
      establishing a therapeutic alliance with the patient and affected family that
      includes patient and family education and agreement on patient-specific goals,
      treatment, follow-up, and monitoring. As pharmacotherapy controls the core
      symptoms of ADHD, the primary care physician and treatment team should discuss
      with the patient other supportive interventions.

PMID- 16961432
TI  - Photosystem II heterogeneity of in hospite zooxanthellae in scleractinian corals
      exposed to bleaching conditions.
AB  - Increased ocean temperatures are thought to be triggering mass coral bleaching
      events around the world. The intracellular symbiotic zooxanthellae (genus
      Symbiodinium) are expelled from the coral host, which is believed to be a
      response to photosynthetic damage within these symbionts. Several sites of impact
      have been proposed, and here we probe the functional heterogeneity of Photosystem
      II (PSII) in three coral species exposed to bleaching conditions. As length of
      exposure to bleaching conditions (32 degrees C and 350 micromol photons m(-2) s(
      1)) increased, the QA- reoxidation kinetics showed a rise in the proportion of
      inactive PSII centers (PSIIx), where QB was unable to accept electrons. PSIIx
      contributed up to 20% of the total PSII centers in Pocillopora damicornis, 35% in
      Acropora nobilis and 14% in Cyphastrea serailia. Changes in Fv/Fm and amplitude
      of the J step along fast induction curves were found to be highly dependent upon
      the proportion of PSIIx centers within the total pool of PSII reaction centers.
      Determination of PSII antenna size revealed that under control conditions in the
      three coral species up to 60% of PSII centers were lacking peripheral light
      harvesting complexes (PSIIbeta). In P. damicornis, the proportion of PSIIbeta
      increased under bleaching conditions and this could be a photoprotective
      mechanism in response to excess light. The rapid increases in PSIIx and PSIIbeta
      observed in these corals under bleaching conditions indicates these physiological
      processes are involved in the initial photochemical damage to zooxanthellae.

PMID- 16961434
TI  - Analysis of light-induced conformational changes of Natronomonas pharaonis
      sensory rhodopsin II by time resolved electron paramagnetic resonance
      spectroscopy.
AB  - The nature and kinetics of the conformational changes leading to the activated
      state of NpSRII/NpHtrII157 were investigated by time-resolved electron
      paramagnetic resonance (TR-EPR) spectroscopy in combination with site-directed
      spin labeling (SDSL) on a series of spin labeled mutants of NpSRII. A structural
      rearrangement of the cytoplasmic moiety of NpSRII upon light activation was
      detected (helices B, C, F and G). The increase in distance between helices C and
      F in the M-trapped state of the complex observed in one double mutant is in line
      with the notion that an outward movement of helix F occurs upon receptor
      activation. The data obtained from the NpSRII/NpHtrII157 complex reconstituted in
      purple membrane lipids are compared with those obtained from the X-ray structure
      of the late M-state of the complex which shows some discrepancies. The results
      are discussed in the context also of other biophysical and EPR experimental
      evidences.

PMID- 16961435
TI  - Characterization of the interactions of fluorescent probes with proteins:
      coumarin 153 and 1,8-ANS in complex with holo- and apomyoglobin.
AB  - In order to provide a thorough characterization of a system with which to study
      the dielectric response of a protein, a well-defined system complex of a
      fluorescent probe and protein is required. We have argued that such a system is
      provided by coumarin 153 and apomyoglobin (Photochem. Photobiol. 79, 440-446
      [2004]). In order to demonstrate further that coumarin 153 exhibits negligible
      nonspecific binding to the surface of apomyoglobin, we study its interactions
      with both the apo and holo proteins. We further make a similar comparison with 8
      anilino-l-naphthalenesulfonic acid, for which an NMR structure with apomyoglobin
      has been obtained. Our results confirm the appropriateness of the system of
      coumarin 153 and apomyoglobin for the investigation of solvation by the protein
      matrix.

PMID- 16961436
TI  - Melanopsin triggers the release of internal calcium stores in response to light.
AB  - Melanopsin is the photopigment that confers photosensitivity upon intrinsically
      photosensitive retinal ganglion cells (ipRGCs). This subset of retinal ganglion
      cells comprises less than 2% of all RGCs in the mammalian retina. The paucity of
      melanopsin-positive cells has made studies on melanopsin signaling difficult to
      pursue in ipRGCs. To address this issue, we have established several cell lines
      consisting of a transformed human embryonic kidney cell line (HEK293) stably
      expressing human melanopsin. With these cell lines, we have investigated the
      intracellular rise in calcium triggered upon light activation of melanopsin. Our
      human melanopsin-expressing cells exhibit an irradiance-dependent increase in
      intracellular calcium. Control cells expressing human melanopsin, where the
      Schiff-base lysine has been mutated to alanine, show no responses to light.
      Chelating extracellular calcium has no effect on the light-induced increase in
      intracellular calcium suggesting that calcium is mobilized from intracellular
      stores. This involvement of intracellular stores has been confirmed through their
      depletion by thapsigargin, which inhibits a subsequent light-induced increase in
      intracellular calcium. Addition of the nonselective cation channel blocker
      lanthanum does not alter light-induced rises in intracellular calcium, further
      supporting that melanopsin triggers a release of internal calcium from internal
      stores. HEK293 cells stably expressing melanopsin have proven to be a useful tool
      to study melanopsin-initiated signaling.

PMID- 16961437
TI  - Intrinsic fluorescence polarization of amniotic fluid: II. Toward a noninvasive
      method for the determination of fetal lung maturity.
AB  - The present study compares two methods for the determination of fetal lung
      maturity: the novel intrinsic fluorescence polarization ratio (IFPR) and the
      commercial TDx-FLMII. Amniotic fluid (AF) samples were collected from 69 women
      during the second and third trimesters of singleton pregnancies. Thirty-three
      samples were tested for IFPR only after centrifugation, and the rest were
      examined both before and after centrifugation. Of the latter 33 samples, 29 were
      assessed for lung maturity with the TDx-FLMII method as well. The results showed
      that IFPR values decreased with the advance in gestational age (r = 0.77, p <
      0.05, n = 69). A significant correlation was found between IFPR of centrifuged
      and noncentrifuged samples (r = 0.94, p < 0.05, n = 36). A significant
      correlation was demonstrated between IFPR and TDx-FLMII values of centrifuged (r
      = 0.75, p < 0.05, n = 29) and noncentrifuged (r = 0.63, p < 0.05, n = 29) samples
      and moreover, samples considered mature by TDx-FLMII had low values of IFPR (n =
      10). It can be concluded that the IFPR method can utilize noncentrifuged AF, thus
      suggested as a potential noninvasive method.

PMID- 16961438
TI  - Health and information in Africa: the role of the journal Rural and Remote
      Health.

PMID- 16961439
TI  - Evaluation of an automated system for prior authorization: a COX-2 inhibitor
      example.
AB  - OBJECTIVE: To evaluate the effectiveness of an automated prior authorization (PA)
      system (SmartPA) in reducing use of and expenditures for cyclooxygenase-2 (COX-2)
      inhibitors. STUDY DESIGN: Before and after with control group. METHODS: After
      implementation of SmartPA in Missouri, changes in use of and expenditures for COX
      2 inhibitors, COX-2 substitutes (traditional nonsteroidal anti-inflammatory drugs
      [NSAIDs] and other products for pain), and gastrointestinal (GI) protective
      agents were compared between the Medicaid program of Missouri and that of a state
      with no PA program for COX-2 inhibitors. Subjects were continuously enrolled for
      the 24-month study period and had a claim for a COX-2 inhibitor in the 12-month
      baseline period. Analyses included comparison of means and linear regression.
      Regressions controlled for age, sex, risk for GI complications, severity of
      illness, and the interaction between state and risk. RESULTS: Changes in
      expenditures for COX-2 inhibitors, NSAIDs, other pain drugs, and GI-protective
      drugs were $256 higher, $56 lower, $21 higher, and $198 higher, respectively, in
      the control state among low-risk patients. Changes in expenditures were $102
      higher, $12 lower, $21 lower, and $185 higher, respectively, in the control state
      among high-risk patients. Results were similar for drug utilization. CONCLUSION:
      Implementation of SmartPA resulted in reduced use of and expenditures for COX-2
      inhibitors and reduced net expenditures for all pain and GI-protective
      medications. These effects were greatest for patients at low risk for GI
      complications.

PMID- 16961440
TI  - The effects of prescription drug copayments on statin adherence.
AB  - BACKGROUND: High copayments may present a barrier to medication adherence among
      patients with chronic conditions such as hyperlipidemia. OBJECTIVE: To assess the
      effects of statin copayments on statin adherence among individuals with employer
      based insurance. STUDY DESIGN: We used a cross-sectional time-series design, with
      patient as the cross section and month as the time unit. METHODS: Medical and
      pharmacy claims among continuously enrolled statin users were selected from the
      2000-2003 Medstat MarketScan database. Generalized estimating equation models
      were used to estimate the effects of copayment changes on statin adherence.
      Adherence was derived from the medication possession ratio, which represents the
      percentage of days on therapy each month. Separate estimates were obtained for
      new statin users (n = 142 341) and for continuing statin users (n = 92 344).
      RESULTS: Higher copayments were associated with lower statin adherence rates. A
      100% index copayment increase had a larger effect on monthly adherence (2.6 and
      1.1 percentage point decreases in adherence among new users and continuing users,
      respectively [both P < .01]) than a 100% copayment increase over time (a 1.1
      percentage point decrease among new users [P < .01] and a nonsignificant decrease
      among continuing users). In all models, new statin users were more price
      sensitive than continuing users. CONCLUSIONS: High copayments are a financial
      barrier to statin adherence. The index copayment amount can affect compliance
      with statin use. Given the relationship between statin use and decreased
      frequency of cardiovascular events and procedures, the implications of high
      copayments should be considered by policy makers.

PMID- 16961441
TI  - Effect of generic-only drug benefits on seniors' medication use and financial
      burden.
AB  - BACKGROUND: Generic-only drug benefits are a way to provide some coverage, as
      opposed to no coverage. OBJECTIVE: To examine how switching from brand name to
      generic-only drug coverage affected seniors' medication use and financial burden.
      STUDY DESIGN: Data are from a 2002 cross-sectional survey conducted for a
      separate study on benefit caps. Participants belonged to a Medicare managed care
      plan in one state and had $2000 capped brand name benefits in 2001 but generic
      only benefits in 2002. METHODS: Participants reported their cost-cutting
      strategies before and after the change to generic-only coverage, the medications
      affected, and their financial burden. We conducted bivariate and multivariate
      analyses of cost-cutting strategies and financial burden before and after
      implementation of generic-only benefits. RESULTS: Among 611 participants (63%
      response), rates of switching medications increased after discontinuation of
      brand name coverage (27% vs 8%, P < .001). Switches were from brand name drugs to
      generic equivalents (14%) (eg, Prozac to fluoxetine hydrochloride), to
      nonequivalent generics (26%) (eg, Paxil to fluoxetine), and to different brand
      name drugs (45%) (eg, Paxil to Zoloft). Ninety percent of brand name switches
      remained in the same therapeutic class (eg, selective serotonin reuptake
      inhibitors). After discontinuation of brand name coverage, participants reported
      higher rates of decreased medication use (28% vs 17%) and greater difficulty
      paying for prescriptions (65% vs 37%) (P < .001 for both). CONCLUSIONS: Changing
      from brand name benefits to generic-only drug coverage led many participants to
      switch to less expensive medications but also decreased medication use and
      increased financial burden. Insurers need to actively help patients adjust to a
      discontinuation of brand name coverage.

PMID- 16961442
TI  - Health plan pay-for-performance strategies.
AB  - OBJECTIVE: To examine health plan strategies, planning, development, and
      implementation of pay-for-performance programs (financial incentives for
      hospitals and physicians tied to quality and efficiency) at the community level,
      focusing on differences across markets. STUDY DESIGN: A fifth round of site
      visits to 12 nationally representative metropolitan areas between January 2005
      and June 2005, based on more than 1000 protocol-driven interviews with
      representatives from health plans, provider organizations, employers, and policy
      makers. METHODS: In each of 12 communities, we interviewed several executives
      from 35 health plans, including chief executive officers, marketing executives,
      and network contracting directors. Additional perspectives were obtained from
      representatives of employers, large medical groups, and hospital systems.
      RESULTS: Growing numbers of health plans are developing and implementing pay-for
      performance programs for physicians and hospitals. Although in their early
      stages, plans' customized programs show substantial design variation within and
      across markets. This design variation reflects local conditions that include
      information technology capabilities, data availability, relative leverage of
      health plans and providers, willingness of providers to participate, and employer
      influence. The concerns of providers include the administrative burden of health
      plans' customized programs and the potential for conflicting financial
      incentives. CONCLUSIONS: Most health plans are committed to pay-for-performance
      programs. Although providers would prefer health plans in their communities to
      use a single standardized set of measures and methods, this is unlikely given
      local market environments. A national effort directed at standardization might
      significantly reduce the extent of customization but also may limit the
      opportunities for local collaboration with providers.

PMID- 16961443
TI  - Physicians' perceptions of relevant prescription drug costs: do costs to the
      individual patient or to the population matter most?
AB  - OBJECTIVES: Physicians may be aware of at least 2 types of costs when
      prescribing: patient's out-of-pocket costs and the actual costs of the
      medication. We evaluated physicians' perceptions about relevant costs for
      prescription drugs and the importance of communication about these costs. STUDY
      DESIGN: Mailed survey to a random sample of 1200 physician members of the
      California Medical Association, and a phone survey of a sample of nonresponders.
      METHODS: Descriptive statistics of survey items, McNemar's test to compare survey
      item responses, and logistic regression to evaluate the relationship between
      physician, practice, and system variables and physicians' perceptions of relevant
      medication costs. RESULTS: Of respondents with correct addresses, 49.6% responded
      to the survey; 13% of nonresponders were contacted by phone. Approximately 91%
      and 80% of physicians reported that it is important to manage patients' out-of
      pocket costs and total medication costs, respectively. When comparing the
      relative importance of managing the 2 types of costs, 59% of physicians agreed
      that managing patients' out-of-pocket costs was more important than managing the
      total medication costs and only 16% disagreed. Physicians believed it was more
      important to discuss out-of-pocket costs than total costs with patients (P <
      .0001), but only 15% of physicians reported discussing out-of-pocket costs
      frequently and 5% reported talking about total medication costs frequently.
      Physicians who managed more Medicare patients had a greater likelihood than
      physicians managing fewer Medicare patients of prioritizing out-of-pocket cost
      rather than total cost management (P = .038), and generalists had a greater
      likelihood than medical subspecialists (P = .046). CONCLUSIONS: Physicians
      prioritize managing out-of-pocket costs over total medication costs. Pharmacy
      benefit designs that use patient out-of-pocket cost incentives to influence
      utilization are addressing the costs to which physicians may be most responsive.
      When physicians face conflicts between managing patients' out-of-pocket costs and
      total costs, they will likely try to protect the patients' resources at the
      expense of the insurer or society. Efforts to align patients', insurers', and
      societies' incentives will simplify prescribing decisions and result in better
      value in prescribing.

PMID- 16961444
TI  - Employer-sponsored insurance coverage of smoking cessation treatments.
AB  - OBJECTIVE: To investigate the costs and benefits of covering smoking cessation
      interventions from insurers' and employers' perspectives. STUDY DESIGN: A Monte
      Carlo model was used to simulate smoking status and health expenditures in a
      hypothetical population of employees over a period of 20 years. METHODS:
      Population characteristics were drawn from the 1997-2002 National Health
      Interview surveys. Multivariate regressions using a number of publicly available
      datasets from 1996-2002 generated transition probabilities for the simulation.
      The costs and benefits of scenarios where smoking cessation treatments were
      covered were compared with a scenario where none were covered. Sensitivity to
      parameter estimates was evaluated. RESULTS: By the final simulation year,
      insurers had benefit-cost ratios of 0.56 to 1.67 with per member per month costs
      of -$0.22 to $0.43. The earliest year at which savings were achieved for insurers
      was year 8. Employers saw benefit-cost ratios of 1.88 to 5.58 by the final
      simulation year with per member per month costs of -$1.23 to -$0.15. Employers
      achieved savings as early as year 3 and as late as year 8. Models were sensitive
      to the rate at which population members were assumed to exit the insurer or
      employer. CONCLUSION: Both insurers and employers may add smoking cessation
      benefits at minimal burden to their members and with potential savings,
      particularly where the population of interest is relatively stable.

PMID- 16961445
TI  - Failure to demonstrate an impact of computerized physician order entry embedded
      reminders.

PMID- 16961446
TI  - The Impact of an HIV and AIDS Life Skills Program on Secondary School Students in
      KwaZulu-Natal, South Africa.
AB  - The evaluation of the Department of Educations' life skills program on HIV and
      AIDS prevention among Grade 9 students in 22 randomly allocated schools in
      KwaZulu-Natal, South Africa, showed only a significant increase in student
      knowledge about HIV/AIDS in the intervention group compared with the control
      group. No effects were found on safe sex practices (condom use, sexual
      intercourse) or on measures of psychosocial determinants of these practices
      (attitude and self-efficacy). A process evaluation among the teachers showed that
      some implemented the program fully (seven schools) and some partially (four
      schools). An exploratory analysis showed that students who received the full
      intervention were more positive in their perceptions about sexual behavior and
      social connectedness (at 10-month follow-up) and reported less sex and more
      condom use (at 6-month follow-up) than students in the partial and control
      groups. These limited effects therefore call for further analysis of the content
      and implementation strategies used in the classroom.

PMID- 16961447
TI  - Efficacy of an American alcohol and HIV prevention curriculum adapted for use in
      South Africa: results of a pilot study in five township schools.
AB  - The high prevalence of HIV among young people in African countries underscores a
      pressing need for effective prevention interventions. Adapting school-based
      prevention programs developed in the United States for use in African schools may
      present an alternative to the time-consuming process of developing home-grown
      programs. The researchers report the results of a pretest-posttest field trial of
      an alcohol/HIV prevention curriculum adapted from an American model and delivered
      to ninth-grade students in five South African township schools. The revised
      intervention was based primarily on the Project Northland alcohol prevention and
      Reducing the Risk safer sex programs. The researchers found significant
      differences in change from baseline to follow-up between students in intervention
      and comparison groups on intentions to use a condom; drinking before or during
      sex; and, among females, sex refusal self-efficacy. The results of the field
      trial suggest that behavioral interventions developed in Western countries may be
      rapidly adapted to work in other cultural contexts.

PMID- 16961448
TI  - A controlled study of a spirituality-focused intervention for increasing
      motivation for HIV prevention among drug users.
AB  - Spiritual Self-Schema (3-S) therapy is a manual-guided intervention for
      increasing motivation for HIV prevention that integrates a cognitive model of
      self within a Buddhist framework suitable for people of all faiths. In this
      controlled study, 72 methadone-maintained clients received either standard care
      and 8 weeks of 3-S therapy, or standard care alone. At treatment completion, 3-S
      clients reported significantly greater increases in spiritual practices,
      expression of spiritual qualities, and motivation for HIV prevention. They were
      also less likely to have engaged in HIV risk behavior. Correlational analyses
      showed that attendance at 3-S therapy sessions was significantly positively
      related to spiritual practice at treatment completion and to motivation for HIV
      prevention, and that both attendance at 3-S sessions and motivation for HIV
      preventive behavior were significantly negatively related to HIV risk behavior.
      Completion of 3-S therapy predicted posttreatment HIV preventive behavior,
      controlling for pretreatment behavior, demographics, and addiction severity
      measures (odds ratio = 8.89; 95% confidence interval = 1.62-48.93).

PMID- 16961449
TI  - A survey of MSM HIV prevention outreach workers in Chennai, India.
AB  - The present formative study sought to describe issues relevant to HIV prevention
      among men who have sex with men (MSM) in South India by surveying 62 MSM outreach
      workers from three non governmental organizations in Chennai. Although 92%
      reported having sex with men, only 74% identified as gay and 27% were married.
      Only half of these men reported having been tested for HIV. More than half of the
      sample reported that they would rather not know they had HIV until they were
      sick, and almost half indicated that they would rather end their life than live
      with the disease. Eighty-five percent of the sample reported having experienced
      varying levels of harassment from police, and 86% reported varying levels of
      harassment from others. These data point to several important barriers to HIV
      prevention among MSM in South India and lay the groundwork for enhancing the use
      of outreach workers to play a role in HIV prevention in this population.

PMID- 16961450
TI  - Gender, work, and HIV risk: determinants of risky sexual behavior among female
      entertainment workers in China.
AB  - We proposed to integrate cognitive and social factors in the study of unprotected
      commercial sex. Data from 159 female entertainment workers from 15 establishments
      in Shanghai who reported commercial sex in the month prior to interview were used
      to test the approach. Two-sample t tests and multivariate logistic regression
      were conducted to examine if and how individual cognitive and social influence
      factors affect the odds of consistent condom use. About 21% of participants
      reported consistent condom use. Both individual cognitive and social influence
      factors were important correlates of condom use; models containing either alone
      suffered significantly in explanatory power. Perceived easiness in condom use was
      the most proximate determinant of condom use. It helped to translate HIV
      knowledge and prevention motivation into behavior and to mediate the impact of
      sexual relationship power. Prevention intervention is urgently needed and should
      focus on self-efficacy training and promoting supportive social and working
      environments.

PMID- 16961451
TI  - Correlates of nonparticipation in an HIV prevention program for MSM.
AB  - Providing HIV prevention services to high-risk individuals remains challenging.
      We assessed factors associated with nonparticipation among high-risk, sexually
      active MSM found eligible to participate in a brief, telephone-delivered HIV
      prevention trial designed to evaluate the efficacy of motivational enhancement
      therapy (the Sex Check). Two levels of nonparticipation are evaluated: eligible
      participants who did versus those who did not complete their baseline/enrollment
      interview, and enrolled participants who did versus those who did not attend any
      of their counseling sessions. Nonenrollers were younger, less educated, more
      closeted, and were more likely to report sex with an injection drug using
      partner. Enrolled participants who did not engage in their counseling session(s)
      were less educated, reported greater use of alcohol and drugs during sex and use
      of injection drugs. Innovative methods to reduce barriers to engaging high-risk,
      sexually active MSM in risk reduction counseling are needed.

PMID- 16961452
TI  - Development of a curriculum to enhance community-based organizations' capacity
      for effective HIV prevention programming and management.
AB  - Community-based organizations (CBOs), particularly minority-based CBOs, are
      instrumental in the delivery of HIV/AIDS prevention programs and services.
      Despite a tremendous need, many CBOs lack the capacity to plan, implement, and
      evaluate targeted prevention interventions to serve culturally diverse
      populations. This article describes a comprehensive, innovative curriculum for
      building capacity within CBOs providing HIV prevention programming. An overview
      of the process through which the Centers for Disease Control and
      Prevention/Association of Schools of Public Health Institute for HIV Prevention
      Leadership evolved is discussed. The development of the curriculum occurred in
      four phases: needs assessment, curricular design, implementation, and evaluation.
      A description of the Institute's evaluation strategies and procedures are
      described. Selected preliminary evaluation results from two cohorts of
      participants indicate significant knowledge gains and high levels of satisfaction
      with the Institute sessions, assignments, and faculty. The Institute's model
      shows promise for the provision of capacity building education at the individual
      and organizational level for community-based professionals implementing HIV
      prevention programs.

PMID- 16961453
TI  - An oxygen imaging system for medical applications: preliminary results.
AB  - The examination of functional processes in tissue is gaining importance in
      medical research. As a result the imaging and monitoring of biochemical
      parameters in vivo is the goal of many imaging methods. One key parameter in
      photodynamic therapy (PDT) is the molecular oxygen concentration. Two-dimensional
      monitoring of oxygen is demanded for PDT but has not yet been achieved. The use
      of optical methods provides a possible means of measuring molecular oxygen. The
      basis of this method is the measurement of the luminescence lifetime of a dye
      that is quenched by molecular oxygen. The molecular oxygen concentration can be
      monitored two-dimensionally by pixel-wise determination of the luminescence
      lifetime with a CCD-camera. A new O(2)-imaging system based on this principle is
      presented in this article. The dye Ru(bpy)(3)(2+) is quenched by molecular oxygen
      and was used in the first experiments with the system.

PMID- 16961454
TI  - [First results of the investigation of the stability and tissue integration of a
      degradable, elastomeric copolymer in an animal model].
AB  - The stability and tight integration into adjacent tissue of a novel, degradable,
      elastic copolymer were examined in an animal model. The biomaterial was used for
      the reconstruction of a gastric wall defect in Sprague-Dawley rats (n=42) to test
      the polymeric material under the extreme chemical, enzymatical and mechanical
      conditions of the stomach. In the control group (n=21) the same defect of the
      gastric wall was primarily closed without biomaterial implantation. In the
      baseline group (n=21) the animals were kept under standard conditions without any
      surgical procedure. The implantation periods were 1 week, 4 weeks and 6 months.
      The animals' weight was determined preoperatively and before explantation. After
      explantation, air was pumped into the stomach and the pressure was measured by
      using a pressure-gauge in order to test whether the surgically produced union of
      the stomach wall and the polymer patch was gas-tight. After 1 week of
      implantation time a statistically significant increase of the body weight of the
      animals was found only in the baseline group. Four weeks and 6 months after the
      abdominal surgical procedure, a statistically significant increase of the
      animals' weight was found in the implantation group, the control and the baseline
      group. Gastrointestinal complications like fistula, perforation or peritonitis
      did not occur in any of the animals. The measurement of the stomach pressure
      after maximal gas insufflation did not show significant differences between the
      implantation group, the control and the baseline group in any of the time periods
      investigated. Despite very high strains of the gastric wall, no gas leakage was
      detected. There was a tight connection between the polymer and the adjacent
      stomach wall in all animals investigated. An adequate mechanical stability of the
      biomaterial was detectable under the extreme pathophysiological conditions of the
      stomach milieu. A fast and unfavourable degradation of the degradable polymer was
      not found in any of the animals. Further investigations are needed to analyse the
      mechanisms of the tissue integration of the biomaterial as well as the
      degradation kinetic of the polymer and the process of the tissue remodeling. The
      knowledge of these processes is necessary to adapt the novel biomaterial and thus
      prepare it for the use and implantation in different body locations and to
      develop novel therapeutical options in medicine.

PMID- 16961455
TI  - [Designing a surgical device for harvesting autologous fascia lata grafts as a
      minimal invasive procedure].
AB  - AIMS: Fascia lata is used in different shapes and sizes as a graft material in
      surgical procedures. The conventional method of harvesting a fascia lata graft is
      through a long skin incision on the lateral aspect of the thigh. Minimal invasive
      procedures have been established to reduce the disadvantages of an extensive
      surgical approach for obtaining the autotransplant. However, they do not
      facilitate to suture the remaining fascia after harvesting the transplant and
      therefore bear the risk of a symptomatic herniation of the muscle belly. The aim
      of this study was to design a surgical device to harvest a fascia lata graft and
      close the resulting fascia defect as a minimal invasive procedure. MATERIALS AND
      METHODS: The prototype was tested in 11 human cadaver specimens. It was
      introduced subcutanously via two small skin incisions. The device contained a
      special fixation- and working mechanism which enabled the fascial closure using a
      continuous suture. After the harvest procedure, both the transplant and the
      sutured fascia lata were examined. RESULTS: The experiments demonstrated the
      suitability of this method for minimal invasive harvesting of fascia lata. The
      removed transplants complied in all experiments with the expected dimensions. The
      continuous suture of the femoral fascia ran with accurate gaps between the
      sutures and constant tension without dehiscence. Neither the transplant nor the
      tissue in the region of harvest have shown unduly macroscopic damage due to the
      use of the device. CONCLUSION: The designed prototype can be used for harvesting
      a fascia lata graft and repairing the resulting defect minimal invasively.
      Clinical implementation seems possible. However, improvements could be made
      mainly concerning the handling of the device.

PMID- 16961456
TI  - [The influence of laser irradiation of low-power density on an experimental
      cartilage damage in rabbit knee-joints: an in vivo investigation considering
      macroscopic, histological and immunohistochemical changes].
AB  - In a total of 45 rabbits, knee-joint arthrosis was induced according to the Hulth
      & Telhag model. Depending on the post-operative survival time, the cartilage was
      investigated macroscopically, histologically and immunohistochemically (within a
      period of 10 days to 8 months). Thereafter, the influence of laser irradiation at
      a wavelength of 692.6 nm and energy densities of 1 and 4 J/cm2 on the cartilage
      morphology seven days following the exposure was examined. After joint
      instability surgery it was found out that the cartilage changes in the main
      stress area (MSA) and in regions outside the main stress area (ROMSA) progressed
      differently. Various qualitative and semi-quantitative changes were found for
      collagens I, II, IV and V, and for the glycoproteins fibronectin and tenascin.
      Immunohistochemically, there was a growing expression of collagen I in the apical
      layers, collagen II showed a stronger pericellular expression, and collagen IV
      showed, after an initial growth of the pericellular expression, a reduced
      territorial expression and a stronger apical-interterritorial expression in the
      osteoarthrotic cartilage. For fibronectin, the cellular expression turned out to
      grow in the ROMSA. In the MSA it decreased, but at the same time the
      interterritorial expression grew. For Tanascin, there was a decrease of the
      interterritorial expression in the radial zone while the pericellular and
      interterritorial expression of the apical layers of the osteoarthrotic cartilage
      grew. Lasing proved to significantly influence the osteoarthrotically changed
      cartilage when applied at an energy density of 1 J/cm2, i.e., the morphological
      changes had not yet progressed to the extent the control group had. Both the
      chondrocyte density and the glucosaminoglycan content turned out to be higher.
      When lasing was applied at higher energy densities, no significant difference
      among the control groups was found. Thus, it could be demonstrated in vivo that
      an arthrotic process decelerates through the influence of laser light of low
      energy densities.

PMID- 16961457
TI  - [Analysis of the periprosthetic femoral bone reaction after uncemented total hip
      arthroplasty with computertomography assisted osteodensitometry in vivo: 6-year
      follow-up].
AB  - AIMS: We prospectively analyzed the cancellous and cortical periprosthetic
      femoral bone reaction after implantation of a cementless total hip arthroplasty
      with computertomography assisted osteodensitometry after a mean of 1 and 6 years.
      MATERIALS AND METHODS: Twenty-one patients (O age at implantation: 52 years) with
      osteoarthrits of the hip joint received 21 cementless hip prostheses with a three
      dimensionally tapered design. All patients were analyzed clinically, with CT
      osteodensitometry and plain radiography after a mean of 10 days, at 1 and 6 years
      postoperatively. Cancellous and cortical bone density was evaluated automatically
      using a special software tool. RESULTS: The proximal region of the stem showed
      progessive cortical (O -15% 1 year, -25% 6 years post-OP) and cancellous (O -26%
      1 year, -49% 6 years post-OP) bone density loss. Cortical bone density loss was
      lower and non-progressive at the diaphysis (O -7% 1 year, -9% 6 years post-OP)
      and the distal region (O -6% 1 year, -4% 6 years post-OP) of the stem. All stems
      showed no signs of loosening on plain radiography and good clinical results
      according to the Harris hip score. CONCLUSION: Computertomography assisted
      osteodensitometry is the only method which allows discrimination between
      periprosthetic cortical and cancellous bone density changes in vivo. The analyzed
      uncemented stem fixates at the diaphysis and distal region. Due to the changed
      biomechanical loading after stem implantation, progressive proximal cancellous
      bone density loss was measured for the first time in vivo. Its role in the
      pathogenesis of implant loosening is still unknown and needs to be further
      elucidated.

PMID- 16961458
TI  - [Influence of patellar position on tibial rotation after total knee
      arthroplasty].
AB  - AIM: Common total knee arthroplasty leads to resection of the anterior cruciate
      ligament. Lacking the ligamentous guidance, tibial rotation depends on different
      factors, i.e., muscle vectors. The present study measured the influence of the
      knee extensor mechanism determined by the mediolateral patella position on tibial
      rotation after implantation of two different knee prostheses. MATERIALS AND
      METHODS: Physiologic tibial rotation and mediolateral patella translation were
      measured in ten fresh-frozen knee specimens. After implantation of the Interax-
      and Genesis II-prosthesis in each five of the ten specimens, kinematic
      measurements were made again with a determination of significant alterations.
      RESULTS: The maximal medial patella position relative to the centre of the tibia
      was -6.6 mm (representing lateralisation); the maximal external tibial rotation
      was 4.1 degrees. After implantation of the Genesis II-prosthesis the external
      tibial rotation was reduced (p=0.03) with a relatively medialised patella
      (p=0.01), whereas after implantation of the Interax-prosthesis the external
      tibial rotation was increased (p=0.01) while the patella was measured to be
      lateralised similar to physiologic conditions. CONCLUSION: The results of the
      current study revealed a potential influence of mediolateral patella position on
      tibial rotation following total knee arthroplasty, while both prosthesis systems
      were not able to reproduce physiologic joint kinematics.

PMID- 16961459
TI  - Drug targeting to the brain.
AB  - The central nervous system (CNS) is a sanctuary site and is protected by various
      barriers. These regulate brain homeostasis and the transport of endogenous and
      exogenous compounds by controlling their selective and specific uptake, efflux,
      and metabolism in the brain. Unfortunately, potential drugs for the treatment of
      most brain diseases are therefore often not able to cross these barriers. As a
      result, various drug delivery and targeting strategies are currently being
      developed to enhance the transport and distribution of drugs into the brain. Here
      we discuss briefly the biology and physiology of the blood-brain barrier (BBB)
      and the blood-cerebro-spinal-fluid barrier (BCSFB), and, in more detail, the
      possibilities for delivering large-molecular-weight drugs by local and global
      delivery and by viral and receptor-mediated nonviral drug delivery to the (human)
      brain.

PMID- 16961460
TI  - A new assay for nitric oxide reductase reveals two conserved glutamate residues
      form the entrance to a proton-conducting channel in the bacterial enzyme.
AB  - A specific amperometric assay was developed for the membrane-bound NOR [NO
      (nitric oxide) reductase] from the model denitrifying bacterium Paracoccus
      denitrificans using its natural electron donor, pseudoazurin, as a co-substrate.
      The method allows the rapid and specific assay of NO reduction catalysed by
      recombinant NOR expressed in the cytoplasmic membranes of Escherichia coli. The
      effect on enzyme activity of substituting alanine, aspartate or glutamine for two
      highly conserved glutamate residues, which lie in a periplasmic facing loop
      between transmembrane helices III and IV in the catalytic subunit of NOR, was
      determined using this method. Three of the substitutions (E122A, E125A and E125D)
      lead to an almost complete loss of NOR activity. Some activity is retained when
      either Glu122 or Glu125 is substituted with a glutamine residue, but only
      replacement of Glu122 with an aspartate residue retains a high level of activity.
      These results are interpreted in terms of these residues forming the mouth of a
      channel that conducts substrate protons to the active site of NOR during
      turnover. This channel is also likely to be that responsible in the coupling of
      proton movement to electron transfer during the oxidation of fully reduced NOR
      with oxygen [U. Flock, N. J. Watmough and P. Adelroth (2005) Biochemistry 44,
      10711-10719].

PMID- 16961461
TI  - Cardiac mitochondrial cGMP stimulates cytochrome c release.
AB  - Although the existence of cardiac mitochondrial cGMP has been reported previously
      [Kimura and Murad (1974) J. Biol. Chem. 249, 6910-6916], the physiological and
      pathophysiological properties of cGMP in cardiac mitochondria have remained
      unknown. The aim of the present study was to clarify whether cardiac
      mitochondrial cGMP regulates the apoptosis of cardiomyocytes. In the presence of
      GTP, the NO donors SNAP (S-nitroso-N-acetyl-DL-penicillamine; 1 mmol/l) and SNP
      (sodium nitroprusside; 1 mmol/l) each markedly increased the cGMP level in a
      highly purified mitochondrial protein fraction prepared from left ventricular
      myocytes of male Wistar rats, and these increases were inhibited by 1 micromol/l
      ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), an inhibitor of NO-sensitive
      guanylate cyclase. In purified mitochondria, both SNAP (1 mmol/l) and the
      membrane-permeant cGMP analogue 8-Br-cGMP (8-bromo-cGMP; 1 mmol/l), but not cGMP
      (1 mmol/l), increased cytochrome c release from succinate-energized mitochondria
      without inducing mitochondrial swelling and depolarization of the mitochondrial
      membrane as factors of activation of MPT (mitochondrial permeability transition).
      The cytochrome c release mediated by SNAP was inhibited in the presence of 1
      micromol/l ODQ. On the other hand, 1 mmol/l SNAP induced apoptosis in primary
      cultured adult rat cardiomyocytes in a time-dependent manner, and this induction
      was significantly inhibited in the presence of ODQ. Furthermore, apoptosis
      induced in primary cultured cardiomyocytes by hypoxia/re-oxygenation was also
      inhibited by ODQ. These results suggest that the acceleration of cGMP production
      in cardiac mitochondria stimulates cytochrome c release from mitochondria in an
      MPT-independent manner, resulting in apoptosis.

PMID- 16961463
TI  - Signal transduction therapy in haematological malignancies: identification and
      targeting of tyrosine kinases.
AB  - Tyrosine kinases play key roles in cell proliferation, survival and
      differentiation. Their aberrant activation, caused either by the formation of
      fusion genes by chromosome translocation or by intragenic changes, such as point
      mutations or internal duplications, is of major importance in the development of
      many haematological malignancies. An understanding of the mechanisms by which BCR
      ABL contributes to the pathogenesis of chronic myeloid leukaemia led to the
      development of imatinib, the first of several tyrosine kinase inhibitors to enter
      clinical trials. Although the development of resistance has been problematic,
      particularly in aggressive disease, the development of novel inhibitors and
      combination with other forms of therapy shows promise.

PMID- 16961462
TI  - The C-terminus of CIS defines its interaction pattern.
AB  - Proteins of the SOCS (suppressors of cytokine signalling) family are
      characterized by a conserved modular structure with pre-SH2 (Src homology 2), SH2
      and SOCS-box domains. Several members, including CIS (cytokine-inducible SH2
      protein), SOCS1 and SOCS3, are induced rapidly upon cytokine receptor activation
      and function in a negative-feedback loop, attenuating signalling at the receptor
      level. We used a recently developed mammalian two-hybrid system [MAPPIT
      (mammalian protein-protein interaction trap)] to analyse SOCS protein-interaction
      patterns in intact cells, allowing direct comparison with biological function. We
      find that, besides the SH2 domain, the C-terminal part of the CIS SOCS-box is
      required for functional interaction with the cytokine receptor motifs examined,
      but not with the N-terminal death domain of the TLR (Toll-like receptor) adaptor
      MyD88. Mutagenesis revealed that one single tyrosine residue at position 253 is a
      critical binding determinant. In contrast, substrate binding by the highly
      related SOCS2 protein, and also by SOCS1 and SOCS3, does not require their SOCS
      box.

PMID- 16961464
TI  - Improved usability of the minimal model of insulin sensitivity based on an
      automated approach and genetic algorithms for parameter estimation.
AB  - Minimal model analysis of glucose and insulin data from an IVGTT (intravenous
      glucose tolerance test) is widely used to estimate insulin sensitivity; however,
      the use of the model often requires intervention by a trained operator and some
      problems can occur in the estimation of model parameters. In the present study, a
      new method for minimal model analysis, termed GAMMOD, was developed based on
      genetic algorithms for the estimation of model parameters. Such an algorithm does
      not require the fixing of initial values for the parameters (that may lead to
      unreliable estimates). Our method also implements an automated weighting scheme
      not requiring manual intervention of the operator, thus improving the usability
      of the model. We studied a group of 170 women with a history of previous
      gestational diabetes. Results obtained by GAMMOD were compared with those
      obtained by MINMOD (a traditional gradient-based algorithm for minimal model
      analysis). Insulin sensitivity by GAMMOD was (3.86+/-0.19) compared with (4.33+/
      0.20) x 10(-4) micro-units.ml(-1) x min(-1) by MINMOD; glucose effectiveness was
      0.0236+/-0.0005 compared with 0.0229+/-0.0005 min(-1) respectively. The
      difference in the estimation by the two methods was within the precision expected
      for such metabolic parameters and is probably of no clinical relevance. Moreover,
      both the coefficient of variation of the estimated parameters and the error of
      fit were generally lower in GAMMOD, despite the fact that it does not require
      manual intervention. In conclusion, the GAMMOD approach for parameter estimation
      in the minimal model provides a reliable estimation of the model parameters and
      improves the usability of the model, thus facilitating its further use and
      application in a clinical context.

PMID- 16961466
TI  - Advances in small animal oncology.

PMID- 16961465
TI  - The activity of the dinuclear cobalt-beta-lactamase from Bacillus cereus in
      catalysing the hydrolysis of beta-lactams.
AB  - Metallo-beta-lactamases are native zinc enzymes that catalyse the hydrolysis of
      beta-lactam antibiotics, but are also able to function with cobalt(II) and
      require one or two metal-ions for catalytic activity. The hydrolysis of
      cefoxitin, cephaloridine and benzylpenicillin catalysed by CoBcII (cobalt
      substituted beta-lactamase from Bacillus cereus) has been studied at different
      pHs and metal-ion concentrations. An enzyme group of pK(a) 6.52+/-0.1 is found to
      be required in its deprotonated form for metal-ion binding and catalysis. The
      species that results from the loss of one cobalt ion from the enzyme has no
      significant catalytic activity and is thought to be the mononuclear CoBcII. It
      appears that dinuclear CoBcII is the active form of the enzyme necessary for
      turnover, while the mononuclear CoBcII is only involved in substrate binding. The
      cobalt-substituted enzyme is a more efficient catalyst than the native enzyme for
      the hydrolysis of some beta-lactam antibiotics suggesting that the role of the
      metal-ion is predominantly to provide the nucleophilic hydroxide, rather than to
      act as a Lewis acid to polarize the carbonyl group and stabilize the oxyanion
      tetrahedral intermediate.

PMID- 16961467
TI  - Clinical approach to renal neoplasia in budgerigars (Melopsittacus undulatus).
AB  - Renal neoplasia in budgerigars (Melopsittacus undulatus) is seen regularly in
      general practice and is of interest to many practicing veterinary surgeons. This
      review article provides an overview of the current knowledge and the most recent
      reports in avian literature regarding renal tumours in budgerigars, with the
      emphasis on clinical diagnosis and treatment. The high prevalence of renal
      neoplasia in budgerigar is discussed, with notes on the most commonly diagnosed
      tumours, possibility of metastases, sex and age predisposition. The possibility
      of ultrasonography and radiography in the diagnosis of this pathological
      condition are compared as well as the possible role of blood and urine analyses.
      Two studies are described, both of which investigate the possible involvement of
      a retrovirus as the aetiological agent.

PMID- 16961468
TI  - Subtotal intracapsular prostatectomy as a useful treatment for advanced-stage
      prostatic malignancies.
AB  - OBJECTIVES: Palliative surgery for advanced-stage prostatic cancers was tested
      with regard to survival rate and complications in a prospective randomised
      clinical study of dogs. Currently, therapeutic approaches have a grave long-term
      prognosis in clinically significant prostatic cancer. METHODS: Of 167 dogs with
      prostatic disorders, 24 were diagnosed with prostatic cancer. Eleven dogs
      underwent subtotal intracapsular prostatectomy, while in 10 dogs total
      prostatectomy was performed. The remaining three dogs were euthanased at their
      owner's request. Dogs treated by subtotal intracapsular prostatectomy and those
      treated by total prostatectomy were followed until their death. RESULTS: It was
      found that dogs treated by subtotal intracapsular prostatectomy survived 5.63
      times longer (mean [sd] 112.0 [63.03] days) than those treated by total
      prostatectomy (19.9 [10.67] days) (P<0.01). Moreover, a significant decrease in
      postoperative complications after subtotal intracapsular prostatectomy was
      recorded, especially with regard to urinary incontinence. CLINICAL SIGNIFICANCE:
      It was concluded that, in the authors' facility, treatment of prostatic cancer by
      subtotal intracapsular prostatectomy was superior to that by total prostatectomy,
      with respect to both postoperative survival and serious complications.

PMID- 16961469
TI  - Prospective evaluation of a peripherally administered three-in-one parenteral
      nutrition product in dogs.
AB  - OBJECTIVES: Peripheral parenteral nutrition is an option for short-term
      nutritional support in dogs which cannot be supported with enteral nutrition. The
      objective of this study was to examine the use of a three-in-one, 840 mOsmol/l
      peripheral parenteral nutrition product containing amino acids, lipids and
      glucose in separate compartments in dogs. METHODS: Nine dogs were administered
      the three-in-one product, and two dogs were administered the amino acid part of
      the product, via a peripheral vein. Dogs were monitored for mechanical and
      metabolic complications. RESULTS: Mechanical complications (apparent thrombus or
      thrombophlebitis) caused failure of infusion at a median of 36 hours. None of the
      dogs appeared to develop catheter-related sepsis. Using a 10-hour infusion period
      appeared to decrease the incidence of line failure. Mild and clinically non
      significant hyperglycaemia was the only metabolic complication. In four of the
      dogs, serum folate, cobalamin and homocysteine concentrations were determined
      before and after peripheral parenteral nutrition administration. Oral and
      parenteral administration of methionine has been previously associated with
      lowered serum folate concentrations. Low serum folates and the subsequent
      hyperhomocysteinaemia have been associated with venous endothelial damage and
      venous thrombus in other species. Serum cobalamin also affects homocysteine
      metabolism. Median serum folate, cobalamin and homocysteine concentrations were
      not affected by the short-term administration of this three-in-one product.
      CLINICAL SIGNIFICANCE: Using the product for 24 hours/day may require catheter
      replacement due to line failure. Other than line failure, which may be improved
      by 10- to 12-hour infusion times, this product was found to be safe and practical
      for short-term peripheral parenteral nutrition in dogs.

PMID- 16961470
TI  - Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis in the
      cavalier King Charles spaniel.
AB  - OBJECTIVES: To record a previously unreported congenital and hereditary condition
      affecting the eyes and skin in the cavalier King Charles spaniel. METHODS:
      Nineteen cases (13 litters) were investigated, with particular reference to eye
      and skin clinical signs. In addition, five generation pedigrees were obtained and
      studied from all cases with the exception of one. RESULTS: The eye signs were due
      to keratoconjunctivitis sicca, a common ocular disease in the dog, but rarely of
      congenital origin. The skin signs were of an ichthyosiform dermatosis; ichthyosis
      being a rare skin disease in the dog. In human beings, ichthyosis is a similar
      disease, mainly inherited and with a neonatal onset, and sometimes accompanied by
      other developmental defects. In the cavalier King Charles spaniel, the coat
      abnormality was noted at birth by the breeders as a 'curly coat', with
      deterioration of the skin signs as the animal became adult. CLINICAL
      SIGNIFICANCE: These two conditions occurring together in this breed is well
      recognised by some breeders but rarely by the veterinary profession. Successful
      treatment is not possible, although some improvement, particularly of the
      keratoconjunctivitis sicca, can be obtained. The probable hereditary nature of
      the condition is an important factor for control.

PMID- 16961471
TI  - Comparison of radiography and magnetic resonance imaging for evaluating the
      extent of nasal neoplasia in dogs.
AB  - OBJECTIVES: Magnetic resonance imaging (MRI) is increasingly used in veterinary
      practice and, in some centres, is part of the diagnostic work-up of small animals
      with nasal disease. However, there are no published studies which critically
      evaluate the use of magnetic resonance imaging for this purpose. The purpose of
      this work was to assess the changes seen using magnetic resonance imaging and to
      compare them with radiography. METHODS: The study included 12 dogs that had
      undergone both radiography and magnetic resonance imaging of the nasal cavity and
      had a histopathological diagnosis of malignant nasal neoplasia. Two pairs of
      board-certified radiologists scored the radiographs and the MRI scans, evaluating
      10 signs of abnormality using a simple scoring system. Magnetic resonance imaging
      features were described in detail, and radiographic and magnetic resonance
      imaging scores for each sign as well as total scores were compared. RESULTS:
      Magnetic resonance imaging often showed that the tumour was more extensive than
      it had appeared on radiography but occasionally showed that radiographs had
      overestimated its size. Although radiography was reliable for assessment of the
      presence and size of a mass and for the extent of turbinate destruction, it
      usually failed to show occlusion of the major airway passages that were evident
      on magnetic resonance imaging. Extension of the tumour into the opposite nasal
      cavity, frontal sinus, orbit and cranial cavity was shown much better on magnetic
      resonance imaging. CLINICAL SIGNIFICANCE: Minor but significant extension beyond
      the nasal cavity, which is important for treatment planning and prognosis,
      requires magnetic resonance imaging for demonstration, although radiography shows
      major changes reliably.

PMID- 16961472
TI  - Surgical resection of a primary tracheal fibrosarcoma in a dog.
AB  - A four-year-old, entire male Rottweiler was presented with a history of
      respiratory distress. A tracheal mass was diagnosed on thoracic radiographs and
      tracheoscopy. Surgical excision of three tracheal rings incorporating the tumour
      was performed. The mass was found to be a low-grade fibrosarcoma. Twenty-four
      months later, the owner reported that there was no recurrence of respiratory
      distress and the dog appeared to be doing well clinically. This case of primary
      tracheal fibrosarcoma suggests that this type of tumour should be listed in the
      differential diagnoses for tracheal neoplasia in dogs and that surgical treatment
      alone may be curative.

PMID- 16961473
TI  - Apocrine adenocarcinoma of possible sweat gland origin in a male rabbit.
AB  - A five-year-old, male crossbreed rabbit was referred for acute caudal abdominal
      swelling. On physical examination, the rabbit was slightly depressed and showed
      an enlarged subcutaneous cyst in the caudal abdomen and an adjacent small,
      ulcerated solid mass. A drainage tube was placed in the cystic area, and surgical
      resection of the solid mass was performed. The histopathological diagnosis of the
      mass was apocrine adenocarcinoma. To the authors' knowledge, this report
      describes the first case of spontaneous apocrine adenocarcinoma of possible sweat
      gland origin in a male rabbit.

PMID- 16961474
TI  - Multiple limbal haemangiosarcomas in a border collie dog: management by lamellar
      keratectomy/sclerectomy and strontium-90 beta plesiotherapy.
AB  - An eight-year-old, neutered, male border collie dog was presented with a six-week
      history of left ocular discomfort and a raised, red mass at the lateral limbus.
      The right eye had been enucleated approximately 12 months previously following
      suspected trauma when the eye had become red and painful. The mass was excised
      using superficial keratectomy/sclerectomy and the surgery site was treated with
      strontium-90 beta radiation. Histopathological findings were consistent with a
      diagnosis of haemangiosarcoma. Immunohistochemical staining showed uniform
      expression of CD31 in neoplastic cells, confirming their endothelial origin. Two
      further treatments with strontium-90 beta radiation were applied to the surgical
      site at weekly intervals. Twenty-six weeks after surgery, a second, raised, red
      limbal mass became apparent at the medial limbus of the left eye. Surgical
      excision and adjuvant strontium-90 beta plesiotherapy were performed as described
      for the initial tumour. Routine histopathological analysis confirmed
      haemangiosarcoma at this site. Eighty-six weeks following the initial
      presentation, no recurrence of ocular haemangiosarcoma was evident.

PMID- 16961475
TI  - Intermandibular malignant mesenchymoma in a crossbreed dog.
AB  - A 12-year-old German shepherd crossbreed dog was presented with a submandibular
      mass that was initially diagnosed as myxosarcoma on incisional biopsy. Chest
      radiographs were taken for staging, and magnetic resonance imaging was performed
      to assess the feasibility of cytoreductive surgery before adjuvant radiotherapy.
      The dog underwent debulking surgery, and histology permitted reclassification of
      the tumour as a malignant mesenchymoma (with myxosarcomatous and osteosarcomatous
      differentiation). The dog was subsequently treated with four fractions of
      radiotherapy given at seven-day intervals and three doses of carboplatin. The dog
      remained stable following therapy until its condition acutely deteriorated, and
      it was euthanased 153 days after surgery. On postmortem examination, there were
      no signs of local tumour recurrence, but metastases were observed both in the
      thorax and in the abdomen.

PMID- 16961476
TI  - What is your diagnosis? Mast cell tumour.

PMID- 16961477
TI  - Lung lobe torsion in a Yorkshire terrier.

PMID- 16961478
TI  - X-linked Chronic Granulomatous Disease.

PMID- 16961479
TI  - Examining the risk of anal sac gland carcinoma in cocker spaniels.

PMID- 16961480
TI  - Plagiarism, copyright violation, and dual publication: are you guilty?

PMID- 16961482
TI  - Afghanistan: an overview of ground water resources and challenges.

PMID- 16961484
TI  - Electrical resistance sensors record spring flow timing, Grand Canyon, Arizona.
AB  - Springs along the south rim of the Grand Canyon, Arizona, are important
      ecological and cultural resources in Grand Canyon National Park and are discharge
      points for regional and local aquifers of the Coconino Plateau. This study
      evaluated the applicability of electrical resistance (ER) sensors for measuring
      diffuse, low-stage (<1.0 cm) intermittent and ephemeral flow in the steep, rocky
      spring-fed tributaries of the south rim. ER sensors were used to conduct a
      baseline survey of spring flow timing at eight sites in three spring-fed
      tributaries in Grand Canyon. Sensors were attached to a nearly vertical rock wall
      at a spring outlet and were installed in alluvial and bedrock channels. Spring
      flow timing data inferred by the ER sensors were consistent with observations
      during site visits, with flow events recorded with collocated streamflow gauging
      stations and with local precipitation gauges. ER sensors were able to distinguish
      the presence of flow along nearly vertical rock surfaces with flow depths between
      0.3 and 1.0 cm. Laboratory experiments confirmed the ability of the sensors to
      monitor the timing of diffuse flow on impervious surfaces. A comparison of flow
      patterns along the stream reaches and at springs identified the timing and
      location of perennial and intermittent flow, and periods of increased
      evapotranspiration.

PMID- 16961485
TI  - A mechanism for anomalous decline in radon precursory to an earthquake.
AB  - Mechanisms for interpreting anomalous decreases in radon in ground water prior to
      earthquakes are examined with the help of a case study to show that radon
      potentially is a sensitive tracer of strain changes in the crust preceding an
      earthquake. The 2003 Chengkung earthquake of magnitude (M) 6.8 on December 10,
      2003, was the strongest earthquake near the Chengkung area in eastern Taiwan
      since 1951. The Antung radon-monitoring station was located 20 km from the
      epicenter. Approximately 65 d prior to the 2003 Chengkung earthquake, precursory
      changes in radon concentration in ground water were observed. Specifically, radon
      decreased from a background level of 780 pCi/L to a minimum of 330 pCi/L. The
      Antung hot spring is situated in a fractured block of tuffaceous sandstone
      surrounded by ductile mudstone. Given these geological conditions, we
      hypothesized that the dilation of brittle rock mass occurred at a rate faster
      than the recharge of pore water and gas saturation developed in newly created
      cracks preceding the earthquake. Radon partitioning into the gas phase may
      explain the anomalous decrease of radon precursory to the 2003 Chengkung
      earthquake. To support the hypothesis, vapor-liquid, two-phase radon-partitioning
      experiments were conducted at formation temperature (60 degrees C) using
      formation brine from the Antung hot spring. Experimental data indicated that the
      decrease in radon required a gas saturation of 10% developed in rock cracks. The
      observed decline in radon can be correlated with the increase in gas saturation
      and then with the volumetric strain change for a given fracture porosity.

PMID- 16961486
TI  - Modeling effects of multinode wells on solute transport.
AB  - Long-screen wells or long open boreholes with intraborehole flow potentially
      provide pathways for contaminants to move from one location to another in a
      ground water flow system. Such wells also can perturb a flow field so that the
      well will not provide water samples that are representative of ground water
      quality a short distance away from the well. A methodology is presented to
      accurately and efficiently simulate solute transport in ground water systems that
      include wells longer than the grid spacing used in a simulation model of the
      system and hence are connected to multiple nodes of the grid. The methods are
      implemented in a MODFLOW-compatible solute-transport model and use MODFLOW's
      Multi-Node Well Package but are generic and can be readily implemented in other
      solute-transport models. For nonpumping multinode wells (used to simulate open
      boreholes or observation wells, for example) and for low-rate pumping wells (in
      which the flow between the well and the ground water system is not
      unidirectional), a simple routing and local mixing model was developed to
      calculate nodal concentrations within the borehole. For high-rate pumping
      multinode wells (either withdrawal or injection, in which flow between the well
      and the ground water system is in the same direction at all well nodes), complete
      and instantaneous mixing in the wellbore of all inflows is assumed.

PMID- 16961488
TI  - The influence of well hydraulics on the spatial distribution of well
      incrustations.
AB  - In many cases, the operation of wells is hampered by the formation of mineral
      incrustations. From field studies, it is known that the distribution of
      incrustations in wells is quite inhomogeneous. Flow models were calculated to
      assess the hydraulic background of this phenomenon. For horizontal flow, the
      screen section facing the natural flow direction receives the majority of the
      total inflow. This phenomenon increases with increasing natural gradients of
      flow. The vertical distribution of water intake is also quite inhomogeneous. In
      partially penetrating wells, the uppermost part of the screen receives much more
      inflow than the deeper screen sections. These flow inhomogenities involve
      elevated flow velocities and may cause increased influx of shallow, oxygenated
      water, all conditions favorable for incrustation growth. Field investigations on
      incrusting wells clearly show that the identified screen areas of elevated flow
      are indeed much more prone to incrustation deposition. Such sections require more
      attention during rehabilitations. A suction flow control device can help to
      homogenize the inflow but can cause elevated entrance loss when affected by
      incrustation buildup itself.

PMID- 16961487
TI  - An assessment of aquifer storage recovery using ground water flow models.
AB  - Owing to increased demands on ground water accompanied by increased drawdowns,
      technologies that use recharge options, such as aquifer storage recovery (ASR),
      are being used to optimize available water resources and reduce adverse effects
      of pumping. In this paper, three representative ground water flow models were
      created to assess the impact of hydrogeologic and operational parameters/factors
      on recovery efficiency of ASR systems. Flow/particle tracking and solute
      transport models were used to track the movement of water during injection,
      storage, and recovery. Results from particle tracking models consistently
      produced higher recovery efficiency than the solute transport models for the
      parameters/properties examined because the particle tracking models neglected
      mixing of the injected and ambient water. Mixing between injected and ambient
      water affected recovery efficiency. Results from this study demonstrate the
      interactions between hydrogeologic and operational parameters on predictions of
      recovery efficiency. These interactions are best simulated using coupled
      numerical ground water flow and transport models that include the effects of
      mixing of injected water and ambient ground water.

PMID- 16961489
TI  - A new method to characterize hydraulic short-circuits in defective borehole
      seals.
AB  - A new approach has been developed to detect, characterize, and quantify hydraulic
      short-circuits in boreholes with faulty seals. The methodology, applicable to an
      aquifer-aquitard-aquifer system, involves a series of successive, constant-rate
      pumping tests in the lower aquifer while determining the leakage rate with a
      simultaneous nonreactive tracer test. During each pumping step, the tracer is
      injected under constant concentration and constant hydraulic head from a
      piezometer in the upper aquifer. If a seal defect exists, the tracer will follow
      the leak and will be recovered from the pumped water. The theoretical equations
      relate the leakage rate, the pumping rate, the concentration of the injected
      tracer, and the recovered concentration. Leakage rates can be determined for any
      pumping rate. The theory is tested using numerical analysis and a full-scale
      field test.

PMID- 16961490
TI  - Containment criterion for contaminant isolation by cutoff walls.
AB  - A rigorous solution is developed from first principles to guide the preliminary
      design of cutoff walls installed to contain the migration of contaminants from
      source zones. The full analytic solution is used to develop a criterion for
      determining the configuration and hydraulics of optimal wall designs. The
      solution is used to demonstrate the interaction between the properties of the
      wall, the Darcy flux, and the concentration of contaminants at the outside face
      of the well. For a particular wall design, the containment criterion can be used
      to estimate the long-term concentration that will develop at the outside face of
      the wall. Alternatively, for a given concentration on the outside face of the
      cutoff wall, the containment criterion can be used to estimate the Darcy flux
      required to balance the outward diffusion of contaminants. The results of
      numerical simulations are presented to evaluate the analytic approach. The
      numerical results confirm that for a wall with known transport properties, a
      specified Darcy flux is associated with a unique outside contaminant
      concentration.

PMID- 16961491
TI  - Influence of small-scale heterogeneities on contaminant transport in fractured
      crystalline rock.
AB  - We present a sequence of purely advective transport models that demonstrate the
      influence of small-scale geometric inhomogeneities on contaminant transport in
      fractured crystalline rock. Special weight is placed on the role of statistically
      generated variable fracture apertures. The fracture network geometry and the
      aperture distribution are based on information from an in situ radionuclide
      retardation experiment performed at Grimsel test site (Swiss Alps). The obtained
      breakthrough curves are fitted with the advection dispersion equation and
      continuous-time random walks (CTRW). CTRW is found to provide superior fits to
      the late-arrival tailing and is also found to show a good correlation with the
      velocity distributions obtained from the hydraulic models. The impact of small
      scale heterogeneities, both in fracture geometry and aperture, on transport is
      shown to be considerable.

PMID- 16961492
TI  - Estimating background and threshold nitrate concentrations using probability
      graphs.
AB  - Because of the ubiquitous nature of anthropogenic nitrate (NO3(-)) in many parts
      of the world, determining background concentrations of NO3(-) in shallow ground
      water from natural sources is probably impossible in most environments. Present
      day background must now include diffuse sources of NO3(-) such as disruption of
      soils and oxidation of organic matter, and atmospheric inputs from products of
      combustion and evaporation of ammonia from fertilizer and livestock waste.
      Anomalies can be defined as NO3(-) derived from nitrogen (N) inputs to the
      environment from anthropogenic activities, including synthetic fertilizers,
      livestock waste, and septic effluent. Cumulative probability graphs were used to
      identify threshold concentrations separating background and anomalous NO(3)-N
      concentrations and to assist in the determination of sources of N contamination
      for 232 spring water samples and 200 well water samples from karst aquifers.
      Thresholds were 0.4, 2.5, and 6.7 mg/L for spring water samples, and 0.1, 2.1,
      and 17 mg/L for well water samples. The 0.4 and 0.1 mg/L values are assumed to
      represent thresholds for present-day precipitation. Thresholds at 2.5 and 2.1
      mg/L are interpreted to represent present-day background concentrations of NO(3)
      N. The population of spring water samples with concentrations between 2.5 and 6.7
      mg/L represents an amalgam of all sources of NO3(-) in the ground water basins
      that feed each spring; concentrations > 6.7 mg/L were typically samples collected
      soon after springtime application of synthetic fertilizer. The 17 mg/L threshold
      (adjusted to 15 mg/L) for well water samples is interpreted as the level above
      which livestock wastes dominate the N sources.

PMID- 16961493
TI  - Developing a long-term monitoring network under uncertain flowpaths.
AB  - A long-term monitoring well network is developed using complementary and simple
      approaches in conjunction with a stochastic ground water flow and transport
      model. The development is illustrated for a case study of a U.S. nuclear testing
      site (Shoal) that is undergoing environmental restoration. The network design
      builds on three different, yet complementary, tools for locating the monitoring
      wells with a main objective of detection monitoring. The first tool is applied to
      select potential siting horizons where monitoring wells could be located. The
      second tool is used to place monitoring wells in locations with high success
      probability. The success here is defined as the detection of migrating stochastic
      plumes before a certain mass percentage reaches a compliance boundary. The third
      tool is used to analyze detection efficiency of multiple combinations of three
      wells. Seventy-six different three-well networks are selected from 20 candidate
      locations and are evaluated for detection efficiency. From the 76 networks
      analyzed, 28 attain detection efficiency close to or above 70%. The results of
      the different analyses provide multiple alternatives for the locations of the
      three wells, which will become part of the long-term monitoring network at Shoal.
      A number of combinations are equally good, and the final choice will depend on
      practical considerations and future agreements between model sponsor and
      regulators.

PMID- 16961494
TI  - Local hydraulic gradient estimator analysis of long-term monitoring networks.
AB  - Three measurements of head at unique locations form a three-point estimator of
      the local magnitude and orientation of the hydraulic gradient. The relative head
      measurement error (RHME) is defined here as the measurement error normalized by
      the head drop across the three-point estimator. Monte Carlo simulation results
      show that estimators with base to height ratios between 0.5 and 5.0 and that are
      large enough to keep the RHME below 0.05 create the most accurate gradient
      estimates and provide criteria for identifying good estimators. These criteria
      are applied to an example ground water monitoring network design problem in the
      Culebra dolomite near the Waste Isolation Pilot Plant repository to both analyze
      temporal changes and modify and expand the current monitoring network. Limiting
      the three-point estimators to those that meet the shape and RHME criteria reduces
      the number of possible estimators by >50% and leads to approximately 1 order of
      magnitude decrease in the average estimated magnitude of the gradient relative to
      using all estimators. Application of these criteria also reduces the variability
      in estimated gradient magnitude and orientation between the two time periods of
      measurements. Redundant wells in the network are identified by removing each
      existing well in turn and determining which removals yield the smallest decrease
      in the number of acceptable estimators. Optimal new well locations are identified
      by mapping the increase in total number of acceptable estimators for a single new
      well placed in the study domain.

PMID- 16961495
TI  - Well vulnerability: a quantitative approach for source water protection.
AB  - The concept of vulnerability of drinking water sources is reviewed, and a
      quantitative approach for assessing well vulnerability for complex three
      dimensional ground water systems is developed. The approach focuses on the
      relative expected impact of potential contaminant sources at unknown locations
      within a well capture zone, providing relative measures of intrinsic well
      vulnerability, including the expected times of arrival of a contaminant, the
      dispersion-related reduction in concentration, the time taken to breach a certain
      quality objective, and the corresponding exposure times. Thus, the result of the
      analysis includes the usual advective travel time information used in
      conventional wellhead protection analysis, plus a set of selected quantitative
      measures expressing the expected impact. The technique is based on adjoint theory
      and combines forward- and backward-in-time transport modeling using a standard
      numerical flow and transport code. The methodology is demonstrated using the case
      study of a complex glacial multiaquifer system in Ontario. The new approach will
      be useful in helping water managers develop more physically based and
      quantitative wellhead protection strategies.

PMID- 16961496
TI  - General database for ground water site information.
AB  - In most cases, analysis and modeling of flow and transport dynamics in ground
      water systems require long-term, high-quality, and multisource data sets. This
      paper discusses the structure of a multisite database (the H+ database) developed
      within the scope of the ERO program (French Environmental Research Observatory,
      http://www.ore.fr). The database provides an interface between field
      experimentalists and modelers, which can be used on a daily basis. The database
      structure enables the storage of a large number of data and data types collected
      from a given site or multiple-site network. The database is well suited to the
      integration, backup, and retrieval of data for flow and transport modeling in
      heterogeneous aquifers. It relies on the definition of standards and uses a
      templated structure, such that any type of geolocalized data obtained from wells,
      hydrological stations, and meteorological stations can be handled. New types of
      platforms other than wells, hydrological stations, and meteorological stations,
      and new types of experiments and/or parameters could easily be added without
      modifying the database structure. Thus, we propose that the database structure
      could be used as a template for designing databases for complex sites. An example
      application is the H+ database, which gathers data collected from a network of
      hydrogeological sites associated with the French Environmental Research
      Observatory.

PMID- 16961497
TI  - Determining anisotropic transmissivity using a simplified Papadopulos method.
AB  - The straight-line method presented by Papadopulos requires a minimum of three
      observation wells for determining the transmissivity tensor of a homogeneous and
      anisotropic aquifer. A simplification of this method was developed for fractured
      aquifers where the principal directions of the transmissivity tensor are known
      prior to implementation, such as when fracture patterns on outcropping portions
      of the aquifer may be used to infer the principal directions. This new method
      assumes that observation wells are drilled along the two principal directions
      from the pumped well, thus reducing the required number of observation wells to
      two. This method was applied for an aquifer test in the fractured Navajo
      Sandstone of southwestern Utah and yielded minimum and maximum principal
      transmissivity values of 70 and 1800 m(2)/d, respectively, indicating an
      anisotropy ratio of approximately 24 to 1.

PMID- 16961498
TI  - Miniaturization of the flowing fluid electric conductivity logging technique.
AB  - An understanding of the hydraulic properties of the aquifer and the depth
      distribution of salts is critical for evaluating the potential of ground water
      for conjunctive water use and for maintaining suitable ground water quality in
      agricultural regions where ground water is used extensively for irrigation and
      drinking water. The electrical conductivity profiles recorded in a well using the
      flowing fluid electric conductivity (FEC) logging method can be analyzed to
      estimate interval-specific hydraulic conductivity and estimates of the salinity
      concentration with depth. However, operating irrigation wells commonly allow
      limited access, and the traditional equipment used for FEC logging cannot fit
      through the small access pipe intersecting the well. A modified, miniaturized FEC
      logging technique was developed for use in wells with limited access. In
      addition, a new method for injecting water over the entire screened interval of
      the well reduces the time required to perform FEC logging.

PMID- 16961499
TI  - A real-time, interactive steering environment for integrated ground water
      modeling.
AB  - We present in this note an innovative software environment, called Interactive
      Ground Water (IGW), for unified deterministic and stochastic ground water
      modeling. Based on efficient computational algorithms, IGW allows simulating
      three-dimensional (3D) unsteady flow and transport in saturated media subject to
      systematic and "random" stresses and geological and chemical heterogeneity.
      Adopting a new computing paradigm, IGW eliminates the fragmentation in the
      traditional modeling schemes and allows fully utilizing today's dramatically
      increased computing power. For many problems, IGW enables real-time modeling,
      visualization, mapping, and analysis. The software environment functions as a
      "numerical laboratory" in which an investigator may freely explore the following:
      creating visually an aquifer system of desired configurations, interactively
      applying stresses and boundary conditions, and then investigating and visualizing
      on the fly the geology and flow and transport dynamics. At any time, a researcher
      can pause to interact dynamically with virtually any aspects of the modeling
      process and then resume the integrated visual exploration; he or she can
      initiate, pause, or resume particle tracking, plume modeling, subscale modeling,
      stochastic modeling, monitoring, and budget analyses. IGW continually provides
      results that are dynamically processed, overlaid, and displayed. It dynamically
      merges modeling inputs and outputs into composite two-dimensional/3D images
      integrating related data to provide a more complete view of the complex interplay
      among the geology, hydrology, flow system, and transport. These unique
      capabilities of real-time modeling, steering, analysis, and mapping expand the
      utility of models as tools for research, education, and professional
      investigations.

PMID- 16961500
TI  - A visual basic spreadsheet macro for recession curve analysis.
AB  - A Visual Basic program for an Excel spreadsheet was written to construct a master
      recession curve (MRC), using the adapted matching strip method, for recession
      analysis of ground water level time series. The program uses five different
      linear/nonlinear regression models to adjust individual recession segments to
      their proper positions in the MRC. The program can also be used to analyze the
      recession segments of other time series, such as daily stream discharge or stage.
      Some examples of field data from Croatia are used to illustrate the usefulness of
      its application.

PMID- 16961501
TI  - Friedrich Schwille: an historical appreciation.

PMID- 16961502
TI  - Does ultraviolet radiation affect vaccination efficacy?

PMID- 16961503
TI  - Delayed complications of sulfur mustard poisoning in the skin and the immune
      system of Iranian veterans 16-20 years after exposure.
AB  - BACKGROUND: Extensive cutaneous burns caused by alkylating chemical warfare agent
      sulfur mustard (SM) have been associated with the severe suppression of the
      immune system in humans. We aimed to study the association between late cutaneous
      and immunological complications of SM poisoning. METHODS: Skin examination was
      performed on all SM-poisoned Iranian veterans in the province of Khorasan, Iran,
      who had significant clinical complications, and their SM intoxication was
      confirmed by toxicological analysis. Light microscopy was performed on eight skin
      biopsies. Blood cell counts, serum immunoglobulin and complement factor, as well
      as flow cytometric, analyses were performed on all the patients. The severity of
      cutaneous complications were classified into four grades and compared with
      hematological and immunological parameters, using Spearman's rank correlation
      test. RESULTS: Forty male subjects, confirmed with SM poisoning 16-20 years
      earlier, were studied. The main objective findings were hyperpigmentation (55%),
      dry skin (40%), multiple cherry angiomas (37.5%), atrophy (27.5%), and
      hypopigmentation (25%). Histopathologic findings were nonspecific and compatible
      with hyperpigmented old atrophic scars. Except for the hematocrit and C4 levels,
      hematological and immunological parameters revealed no significant correlation
      with the severity grades of cutaneous complications. CONCLUSION: Sulfur mustard
      is an alkylating agent with prolonged adverse effects on both the skin and the
      immune system. Although skin is a major transporting system for SM's systemic
      absorption, there is probably no correlation between the severity of late
      cutaneous and immunological complications of SM poisoning.

PMID- 16961504
TI  - Monoclonal gammopathies and malignancies in patients with chronic urticaria.
AB  - BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) has been
      described in association with chronic urticaria (CU) in patients with Schnitzler
      syndrome. Chronic urticaria may be a manifestation of hematologic malignancies.
      METHODS: This study was conducted to evaluate the frequency and characteristics
      of MGUS or malignancy in patients with CU. The Mayo Clinic electronic database
      was reviewed to identify patients with the diagnosis of CU. RESULTS: Of the 1639
      patients presenting with CU between 1994 and 2001, 797 (49%) underwent laboratory
      evaluation for the presence of a coexisting monoclonal protein. Forty-seven CU
      patients had MGUS, 142 had a malignancy, and 24 had both. Fifteen percent of CU
      patients with MGUS had a hematologic malignancy compared with 0.9% of CU patients
      without MGUS (P < 0.001). Patients presenting with a new diagnosis of CU at an
      older age (> 56 years) were more likely to have associated underlying MGUS. The
      occurrence of MGUS in this group was higher than the reported incidence of MGUS
      in the general population. CONCLUSIONS: Patients with CU younger than 43 years
      were unlikely to have associated MGUS or malignancy. A higher percentage of
      patients with CU and MGUS had an associated diagnosis of hematologic malignancy.

PMID- 16961505
TI  - Cutaneous squamous cell carcinoma of the lower limbs in Goiania, Goias, Brazil.
AB  - BACKGROUND: Cutaneous squamous cell carcinoma is a common malignant neoplasm that
      affects areas that are exposed to the sun in fair-skinned people. It occurs less
      frequently on the lower limbs where other etiological factors are involved.
      OBJECTIVE: To determine the epidemiological aspects of cutaneous squamous cell
      carcinoma of the lower limbs in Goiania. METHODOLOGY: Forty-three cases of
      cutaneous squamous cell carcinoma of the lower limbs from the Cancer Registry of
      the Population Base of Goias, for the period between 1995 and 1999, were included
      in the study. RESULTS: Among the cases of cutaneous squamous cell carcinoma
      registered in this 5-year interval, 43 (4.6%) represented cases affecting the
      lower limbs. Of these individuals, seven (16.3%) were male and 36 (83.7%) female
      (P < 0.001). Those in the age group of 60 years and above represented 90.7% of
      the cases (P < 0.001). None of the patients had metastasis. CONCLUSION: Cutaneous
      squamous cell carcinomas on the lower limbs are more frequently seen in women
      older than 60 years of age, and they rarely metastasize.

PMID- 16961506
TI  - Microscopic study of normal skin in cases of mycosis fungoides.
AB  - BACKGROUND: During therapy of patients with mycosis fungoides (MF) at the
      Department of Dermatology, Kasr El-Aini Hospital, follow-up biopsies are
      routinely taken every 2 months. It was noticed that lesions of MF might become
      clinically normal during treatment, and yet still show microscopical evidence of
      MF. This finding raised the possibility that clinically normal skin in MF could
      be microscopically involved. AIM: The aim of our work was to evaluate the degree
      of histopathological involvement of normal-looking skin in patients with MF.
      PATIENTS AND METHODS: Thirty patients with stage IB were biopsied from their
      normal skin. Two biopsies were taken: one proximal (2 cm) and the other distal (>
      5 cm) from any visible lesion. Ten normal controls were included in the study.
      All specimens were stained with H&E and examined microscopically. The
      microscopical diagnosis was confirmed by immunophenotyping. RESULTS:
      Epidermotropism was detected in 21 (70%) of the proximal skin biopsies and 14
      (47%) of the distal skin biopsies, whereas no biopsy from the control group
      showed epidermotropism. All the proximal skin biopsies showed dermal infiltrate
      and 90% of the biopsies from the distal normal skin showed dermal infiltrate
      (mostly superficial perivascular). CONCLUSION: Normal skin in patients with MF
      could be affected microscopically and this may raise questions regarding the
      credibility of the current staging classification of MF, and may necessitate
      taking biopsies from normal skin before starting topical treatment. During MF
      treatment, biopsies from cured lesions are required before starting withdrawal.

PMID- 16961507
TI  - Autoimmune subepidermal blistering diseases in Uganda: correlation of
      autoantibody class with age of patients.
AB  - BACKGROUND: No data are available on the incidence and immunoreactivity of
      autoimmune subepidermal blistering skin diseases in East Africa. METHODS: All
      patients with frank blisters/erosions on the skin and/or mucous membranes that
      attended the Department of Dermatology at Mbarara University, Uganda, from May
      2000 to June 2002, were investigated. The diagnosis was based on the clinical
      presentation and on the presence of circulating autoantibodies detected by
      indirect immunofluorescence microscopy on 1 m NaCl-split human skin and by
      Western blotting of recombinant and cell-derived forms of BP180, BP230, and type
      VII collagen. RESULTS: Twenty-two patients with autoimmune subepidermal
      blistering skin disorders were identified, including nine with bullous pemphigoid
      (41%), four with linear immunoglobulin A (IgA) disease (18%), three with mucous
      membrane pemphigoid (14%), two with linear IgG/IgA bullous dermatosis (9%), and
      one each with cicatricial pemphigoid and epidermolysis bullosa acquisita (5%). In
      addition, two patients with immunoreactivity to both the epidermal and dermal
      side of salt-split skin by indirect immunofluorescence microscopy, who were
      unreactive to type VII collagen, were provisionally diagnosed as "mixed
      pemphigoid" (9%). In patients with subepidermal blistering diseases, IgG
      reactivity correlated significantly with old age, whereas younger patients
      preferentially developed IgA autoantibodies (P = 0.024). CONCLUSIONS: The age of
      patients with autoimmune subepidermal blistering diseases appears to influence
      the immunoglobulin class of autoantibodies. The high frequency of IgA
      autoantibodies in Ugandan patients may be explained by the age distribution of
      the Ugandan population.

PMID- 16961508
TI  - Hypocomplementemic urticarial vasculitis: a rare presentation of systemic lupus
      erythematosus.
AB  - BACKGROUND: Urticarial vasculitis is a small-vessel vasculitis, presenting
      clinically as persistent urticarial skin lesions and microscopically as
      leucocytoclastic vasculitis. Hypocomplementemic urticarial vasculitis syndrome
      (HUVS) is a distinct type of urticarial vasculitis with multiorgan involvement,
      whose etiology and link with other diseases are still unknown. Some authors have
      suggested that HUVS can be accompanied by systemic lupus erythematosus (SLE), and
      others believe that it is a rare subtype of SLE. Urticarial vasculitis is seen in
      7-8% of SLE, while 50% of HUVS patients are diagnosed with SLE. OBSERVATIONS AND
      RESULTS: We report a case of HUVS associated with SLE with fatal outcome
      unresponsive to the combination of systemic corticosteroids and azathioprine.
      CONCLUSIONS: SLE and HUVS share both clinical and laboratory features and are
      probably not separate entities. It is mostly likely that HUVS and SLE fall into
      the same spectrum of autoimmune diseases. HUVS is probably a subset of SLE. As
      both diseases can fatally, it should be kept in mind that the overlap of SLE and
      HUVS may exhibit a relatively rapid progression and poor prognosis.

PMID- 16961509
TI  - Fixed drug eruption in Nigeria.
AB  - Fixed drug eruption (FDE) causes cosmetic embarrassment in Nigerian patients,
      particularly when the characteristic hyperpigmented patches affect the face and
      lips. Drugs that have been implicated in the etiology of FDE, and the sites of
      lesions, may vary from country to country. Antimalarials, such as Fansidar,
      Fancimef, Maloxine, Amalar, and Metakelfin, were the most common offending
      agents, accounting for 38% of FDEs, followed by trimethoprim + sulfamethoxazole
      (co-trimoxazole) (28%), dipyrones (10%), Butazolidin (6%), thiacetazone (6%),
      metronidazole (4%), paracetamol (3%), and naproxen (3%). Lesions induced by the
      combination of sulfadoxine and pyrimethamine (in antimalarials) mainly involved
      the face and lips. In most cases, patients took these sulfa-containing
      antimalarials in combination with numerous other drugs, particularly analgesics.
      Unlike chloroquine-induced pruritus, which affects most Africans, the association
      between antimalarials and FDE has not been well documented in our region. Co
      trimoxazole was associated more often than antimalarials with FDEs involving the
      mucocutaneous junctions of the genitalia and lips. Males with genital lesions on
      the glans penis represented 11 (48%) of those with co-trimoxazole
      hypersensitivity. The trunk and limbs were affected mainly by pyrazoles and
      Butazolidin, respectively; however, solitary lesions on the trunk were usually
      due to co-trimoxazole, whereas solitary lesions on the limbs were associated with
      Butazolidin.

PMID- 16961510
TI  - Ivermectin treatment of three cases of demodecidosis during human
      immunodeficiency virus infection.
AB  - Demodecidosis is an ectoparasitosis that is infrequently observed in subjects
      with human immunodeficiency virus (HIV) infection. It has a rosacea-like
      presentation. We present three cases in patients with acquired immunodeficiency
      syndrome (AIDS). Two of these patients had a profuse eruption, and all three
      cases were cured by ivermectin. The single-dose treatment could be repeated in
      cases of subsequent recurrence. Ivermectin thus seems to be a good alternative in
      the treatment of demodecidosis in patients with HIV infection.

PMID- 16961511
TI  - Incidence of multiple myiases in breasts of rural women and oral infection in
      infants from the human warble fly larvae in the humid Tropic-Niger Delta.
AB  - Twenty-eight rural women of the Niger Delta were infected with the human warble
      fly (Tumbu fly) larva, Cordylobia anthropophaga, and of the women examined, 22
      (78.5%) were nursing-mothers. Among the percentage of women with cutaneous
      myiasis, 20 had multiple myiases in their breasts. Larvae were also extracted
      from the upper and lower lips of breast-fed infants. A positive correlation was
      drawn between the incidence of breast and oral myiases.

PMID- 16961512
TI  - Onychoprotothecosis: report of the first case in Brazil.
AB  - The present report describes a case of onychoprotothecosis caused by Prototheca
      wickerhamii in a nonimmunocompromized female. Dermatological examination showed
      yellowish discoloration of the left and right forefinger nails, showing
      onicolysis and hyperkeratosis. The repeated isolation of the algae Prototheca
      (organisms morula-like) as well as the repeated culture in media, Sabouraud agar,
      confirmed the diagnosis. The patient was successfully treated with tioconazol 1%
      topic solution. The aim of this paper was to present a rare condition.

PMID- 16961513
TI  - Cutaneous Crohn's disease.

PMID- 16961514
TI  - Generalized linear porokeratosis.
AB  - A 23-year-old woman was seen for widespread skin lesions present since the age of
      2.5 years. Twenty years ago, she developed a brown macular lesion on her right
      buttock. The lesion became hyperkeratotic and subsequently spread through the
      posterior aspect of her right leg. It later spread to the right side of the trunk
      and to the right arm. When she was 9 years old, she developed similar lesions on
      her left arm and leg. After she was 13 years old, no new skin lesions appeared.
      There was no family history of similar lesions. On examination, there were
      numerous linear and whorled, reddish-brown, hyperkeratotic plaques, with central
      atrophy and raised borders, following Blaschko's lines on all of the extremities.
      These lesions on the extremities extended to the dorsum of the hands and feet
      (Fig. 1). She had hyperkeratotic lesions on the pressure points of both of the
      soles, but no palm involvement. The number of lesions on the right side was
      greater than that on the left. Reddish-brown annular plaques with central atrophy
      and raised borders, appearing in zosteriform configuration, and numerous
      individual 2-3-mm erythematous lichenoid papules were observed on the right side
      of the thorax and the right inguinal region (Fig. 2). No face, scalp, or mucous
      membrane involvement was seen. The nails of the second and fifth fingers of the
      right hand and the nail of the third finger of the left hand showed nail
      dystrophy with longitudinal ridges and pterygium. All the nails of the right foot
      and the nails of the first and fifth toes of the left foot showed dystrophic
      changes with subungual keratosis. The patient was otherwise in good health. Two
      biopsy specimens taken from a hyperkeratotic plaque and a lichenoid papule showed
      an epidermal invagination with angulated parakeratotic tier, denoting cornoid
      lamella. The epidermis just underneath the cornoid lamella displayed
      vacuolization and the granular layer was absent. The adjacent epidermis was
      atrophic, and hydropic degeneration within the basal cell layer was seen. In the
      dermis, a nonspecific, mild, chronic, inflammatory cell infiltrate,
      telangiectatic vessels, and pigment-laden macrophages were present. These
      findings were consistent with linear porokeratosis (Fig. 3). Microscopic
      examinations and mycologic cultures of the nails were negative. We decided to
      treat our case systemically with retinoids, but the patient refused this therapy.
      So, topical tretinoin 0.05% was started once a day. A marked improvement was
      observed in hyperkeratosis through the first 4 weeks of treatment and plateaued
      at 8 weeks. After 10 weeks, the lesions had almost disappeared. We planned to
      continue the applications every other day. One year later, she remains stable
      with application of topical tretinoin 0.05% twice a week and is satisfied with
      the final appearance. She is under regular follow-up.

PMID- 16961515
TI  - Psoriasiform and palmoplanter pustular lesions induced after Kawasaki disease.
AB  - A 7-month-old boy was referred to us because of psoriatic lesions on the
      bilateral cheeks and on the extensor region of the left upper arm at the same
      site of his vaccination for tuberculosis 4 months previously (Fig. 1a,b). He also
      presented with small pustules scattered on the palms and soles (Fig. 1c).

PMID- 16961516
TI  - Subcutaneous panniculitis-like T-cell lymphoma presenting as venous stasis
      ulceration.

PMID- 16961517
TI  - Cutaneous sclerosing perineurioma of the digit.
AB  - An 11-year-old Japanese girl noticed a small nodule, with mild tenderness, on the
      right index finger 5 years before visiting our outpatient clinic. She had no
      familial history of neurofibromatosis or past history of traumatic injury at the
      site of the tumor. Physical examination revealed a slightly elevated,
      subcutaneous, nodular tumor in the volar aspect between the proximal and distal
      interphalangeal joints of the digit (Fig. 1A). By magnetic resonance imaging
      examination, the tumor showed low density on both T1- and T2-weighted images, and
      was located just adjacent to the tendon with no invasive signs. The tumor was
      extirpated; at operation, it was well circumscribed and mobile without adhesion
      to adjacent tendon or nerve, and was easily removed. Grossly, the tumor was a
      well-circumscribed, firm nodule (10 mm x 8 mm x 5 mm in size) (Fig. 1B). The cut
      surface was whitish, homogeneous, and solid without cystic lesions.
      Histologically, it was an unencapsulated, paucicellular dense, fibrous nodule
      with a concentric circular arrangement of collagen bundles (Fig. 2A). Amongst the
      fibrous bundles, a small number of ovoid/epithelioid or plump spindle cells were
      arranged in a corded, trabecular, or whorled (onion bulb-like) pattern (Fig. 2B);
      a storiform pattern was not noted. These cells were relatively uniform and had a
      somewhat elongated, slightly hyperchromatic nucleus with fine granular chromatin.
      Neither nuclear pleomorphism nor multinucleated cells were evident, and necrosis
      and mitotic figures were not observed. Periodic acid-Schiff (PAS) stain after
      diastase digestion highlighted the corded or whorled pattern of the tumor cells
      by encasing them. For immunohistochemical examination, formalin-fixed, paraffin
      embedded serial tissue sections were stained by a labeled streptavidin-biotin
      method. The tumor cells were positive for vimentin and epithelial membrane
      antigen (EMA) (Fig. 3A), and negative for pan-cytokeratin, carcinoembryonic
      antigen (CEA), CD34, alpha-smooth muscle actin, desmin, and CD68. Type IV
      collagen and laminin (Fig. 3B) were detected along the cords or whorls of the
      tumor cells, similar to the staining pattern of the diastase-PAS reaction.
      Schwann cells and axonal components, immunoreactive for S100 protein and
      neurofilament, respectively, were focally detected just adjacent to the cords or
      whorls, although the tumor cells per se did not express these proteins.
      Consequently, the tumor was found to be perineurial in origin and was diagnosed
      as cutaneous sclerosing perineurioma.

PMID- 16961518
TI  - Bullous pemphigoid in a patient with psoriasis during the course of PUVA therapy:
      study by ELISA test.
AB  - A 65-year-old woman had a history of deep vein thrombosis and depression.
      Psoriasis was diagnosed in 1986 and various topical and systemic therapies,
      singly or in combination, were prescribed: tar, topical corticosteroids,
      cyclosporine, etretinate, and methotrexate. Two courses of oral and one course of
      bath psoralen plus UVA (PUVA) therapy (cumulative dose, 467 J/cm(2)) and UVB
      (2.96 J/cm(2)) had been given. In January 1999, she developed a flare of
      generalized psoriasis. In May 1999, therapy with PUVA (8-methoxypsoralen) plus
      topical acetonide triamcinolone 0.1% was initiated. At the time, she was taking
      acenocoumarol, lorazepam, and hydroxyzine chlorhydrate. In August 1999, at
      session 30, when the dose of UVA was 9 J/cm(2), and the total dose was 205
      J/cm(2), a bulla appeared on the dorsum of the toe and was controlled with
      topical antibiotics. Five further sessions of PUVA were given and a generalized
      itching bullous eruption appeared all over the body. PUVA was stopped and the
      patient was hospitalized. On physical examination, extensive psoriatic plaques
      plus vesicles and bullae on the normal skin and on psoriatic lesions were
      observed all over the body (Fig. 1). Histopathologic study of a lesion showed a
      subepidermal vesicle containing fibrin, neutrophils, and a few eosinophils. No
      sunburn cells were observed (Fig. 2). The direct immunofluorescence (DIF) test of
      perilesional uninvolved skin revealed immunoglobulin G (IgG) (Fig. 3) and C3 at
      the dermal-epidermal junction. The DIF study using the patient's skin, previously
      treated with 1 m NaCl, localized the IgG at both the epidermal and dermal sides
      of the basement membrane zone (Fig. 4). Bullous pemphigoid (BP) was diagnosed and
      therapy with prednisone (60 mg/day) was started. The disease was well controlled
      in 3 weeks. The dose of prednisone was tapered and stopped 20 months later,
      without any recurrence. Study of the antibodies by the indirect
      immunofluorescence (IIF) test, using monkey esophagus and guinea pig as
      substrate, was positive at a titer of 1/160 in September 1999. The titer
      decreased to 1/10 in January 2000, and was negative in July 2000. An enzyme
      linked immunosorbent assay (ELISA) test, performed using the commercial kit MBL,
      which identifies antibodies directed against epitopes of the extracellular
      fragment NC16 of antigen 2 of BP, was positive at 15 U/mL (normal value, < 9
      U/mL) in September 1999, and negative in July 2000 (Table 1).

PMID- 16961519
TI  - Paraneoplastic pemphigus resembling linear IgA bullous dermatosis.
AB  - A 69-year-old Chinese man presented in 2001 with a blistering eruption over the
      upper and lower limbs associated with oral ulceration for 1 month. He had stage
      IIIA follicular small cell cleaved non-Hodgkin's lymphoma diagnosed 5 years
      previously, and had received several lines of palliative chemotherapy, including
      two courses of chlorambucil, six cycles of cyclophosphamide, adriamycin,
      vincristine, and prednisolone (CHOP), and two four-cycle courses of rituximab,
      with disease stabilization at the time of presentation. Examination revealed
      erythematous, annular plaques with raised, urticarial borders studded with tense
      bullae and vesicles over the thighs. Some lesions were arciform and annular, with
      vesicles arranged in a ring at the border (Fig. 1). There was involvement of the
      feet with desquamation at the tips of the toes (Fig. 2). Severe erosions with
      hemorrhagic crusts on the lips, tongue, and buccal mucosa were seen. Herpes
      simplex virus serology was negative. A biopsy specimen from a vesicle on the left
      thigh showed suprabasal acantholysis (Fig. 3), some apoptotic keratinocytes (Fig.
      4), satellite cell necrosis in the epidermis, and a superficial perivascular
      infiltrate of lymphocytes and eosinophils. Direct immunofluorescence showed
      intercellular immunoglobulin G (IgG) and C3 within the epidermis and along the
      basement membrane zone. Indirect immunofluorescence on monkey esophagus was
      positive for anti-intercellular antibody at a titre of 1/160 and positive on rat
      bladder at a titre of 1/80. A presumptive diagnosis of paraneoplastic pemphigus
      was made. This was later confirmed by the presence of antibodies against
      envoplakin (210 kDa), periplakin (190 kDa), and desmoglein 1 on
      immunoprecipitation studies. He was started on prednisolone 60 mg/day (1
      mg/kg/day), with complete resolution of skin lesions within 1 week, but
      persistence of oral ulcers. Cyclophosphamide was added at a low dose of 1
      mg/kg/day as he had baseline leukopenia. Cyclosporine was later added to a
      maximum of 4 mg/kg/day with only mild improvement of the oral lesions. He
      declined rituximab therapy. He died 2 months later from fulminant pneumonia.

PMID- 16961520
TI  - Lingual traumatic ulceration (Riga-Fede disease).
AB  - An 11-month-old male infant was referred to our clinic because of a painful ulcer
      of approximately 5 months' duration on the ventral surface of the tongue (Fig.
      1). On physical examination, the lesion was circular (3 cm x 2 cm) with
      erythematous, raised, and indurated borders. No pathologic findings emerged from
      the laboratory data, neurologic examination, or clinical history. The family
      history was also negative for developmental disorders and congenital syndromes.
      No biopsy was performed in view of the age of the infant, the particular site of
      the lesion, and the clinical evidence of diagnosis. The treatment included
      odontologic cream (methylvinylether/maleic acid) as a protective shield, a
      collutorium (chlorhexidine 0.2%), and the use of a teething ring. Complete
      healing of the lesion (Fig. 2) occurred within 3 weeks.

PMID- 16961521
TI  - Successful treatment of a widespread cutaneous Mycobacterium fortuitum infection
      with levofloxacin.

PMID- 16961522
TI  - Elastofibroma dorsi: histologic and echographic considerations.
AB  - BACKGROUND: Elastofibroma dorsi is a relatively rare soft-tissue tumor of the
      elderly with typical localization to the subscapular area. To date, few cases
      have been reported in the dermatology literature. The differential diagnosis
      includes frequently observed subcutaneous neoplasms such as lipoma, fibrolipoma
      or more aggressive tumors. The diagnosis is made with histologic examination.
      CASE REPORT: We present a typical case of elastofibroma dorsi, studied with
      ultrasound investigation and color-power Doppler, and discuss the correlation
      with the histologic picture. CONCLUSIONS: Considering the strict correspondence
      between the characteristic histologic findings of elastofibroma and the specific
      ultrasound pattern, we believe that ultrasound investigation with color and power
      Doppler allows, in typical cases, a definitive diagnosis of elastofibroma.

PMID- 16961523
TI  - Treatment of lichen sclerosus with antibiotics.
AB  - Current therapy for lichen sclerosus centers on topical steroids, particularly
      clobetasol propionate. As some evidence suggests an infectious etiology owing to
      Borrelia, we studied the effect of penicillin and cephalosporin therapy on
      patients with lichen sclerosus who had responded poorly to treatment with potent
      topical corticosteroids. Fifteen patients with lichen sclerosus were treated for
      3-21 months with either penicillin or cephalosporins in an observational study.
      Thirteen patients (nine women, four men) received penicillin, including
      intramuscular penicillin G benzathine suspension and/or oral penicillin V
      potassium, amoxicillin, or amoxicillin/clavulanate potassium. Two additional men
      received cephalosporins, either intramuscular ceftriaxone sodium or oral
      cefadroxil monohydrate. All patients showed a significant response, evident
      within a few weeks. Most striking was the rapid relief of pain, pruritus and
      burning. Four patients cleared completely, four experienced marked improvement,
      and the remaining seven had a favorable improvement of symptoms with incomplete
      clearing of lesions. We recommend treatment of lichen sclerosus with either
      intramuscular ceftriaxone every 3 weeks or intramuscular penicillin every 2-3
      weeks. The addition of oral penicillin or cephalosporin presumably helps maintain
      antibiotic blood levels and may be a sufficient treatment in some cases.

PMID- 16961524
TI  - Psoriasis narratives: how qualitative research is of value in dermatology
      research.

PMID- 16961525
TI  - Cutaneous paragonimiasis with flare up after treatment: a clinical case from
      Laos.

PMID- 16961526
TI  - The search for topical treatments for seborrheic keratoses continues.

PMID- 16961527
TI  - Drug-induced subacute cutaneous lupus erythematosus resulting from ticlopidine.

PMID- 16961528
TI  - Clinical recurrence of actinic keratosis following marginal biopsy: a
      retrospective study.

PMID- 16961529
TI  - Comparison of intralesional meglumine antimoniate, cryotherapy and their
      combination in the treatment of cutaneous leishmaniasis.

PMID- 16961530
TI  - Ice cream headaches with cryotherapy of actinic keratoses.

PMID- 16961531
TI  - Intravenous immunoglobulin in toxic epidermal necrolysis.

PMID- 16961532
TI  - Granuloma annulare associated with hypercalcemia secondary to
      hyperparathyroidism.

PMID- 16961533
TI  - Subungual squamous cell carcinoma of the first toe.

PMID- 16961534
TI  - Pemphigoid gestationis complicating a pregnancy following in vitro fertilization
      and intracytoplasmic sperm injection.

PMID- 16961535
TI  - "Intriguing" repercussions of primary neuritic leprosy during the evolution of
      leprosy across the leprosy spectrum.

PMID- 16961536
TI  - Erythema multiforme-like drug eruption caused by sennoside.

PMID- 16961537
TI  - Muir-Torre syndrome: a case of two brothers.

PMID- 16961538
TI  - Azithromycin, ineffective in the treatment of old-world cutaneous leishmaniasis.

PMID- 16961539
TI  - A novel keratin 9 gene mutation (Met156Arg) in a Japanese patient with
      epidermolytic palmoplantar keratoderma.

PMID- 16961540
TI  - Successful treatment with topical tetracycline of oral white sponge nevus
      occurring in a patient with systemic lupus erythematosus.

PMID- 16961541
TI  - A case of juvenile subcorneal pustular dermatosis successfully treated with
      acitretin.

PMID- 16961542
TI  - Pimecrolimus is effective in Fox-Fordyce disease.

PMID- 16961543
TI  - Scalp necrosis and ulceration secondary to heroin injection.

PMID- 16961544
TI  - Regression of secondary plane xanthomas using cyclosporine A.

PMID- 16961545
TI  - Serum and erythrocyte adenosine deaminase activities in patients with Behcet's
      disease.
AB  - OBJECTIVES: Adenosine deaminase (ADA) is a non-specific marker of the activation
      of the T cell, which has an important role in the etiology of Behcet's disease
      (BD). The purpose of this study was to investigate the determination of ADA
      activity as an index of T-lymphocyte function in BD, which is known to have an T
      cell-mediated immune response. MATERIALS AND METHODS: Adenosine deaminase
      activities in both serum and erythrocytes were measured in 23 untreated patients
      with BD and in 20 healthy controls. The patients with BD were divided into two
      groups: active (n = 10) and inactive (n = 13). RESULTS: When compared with the
      control group, serum ADA activity was high (P < 0.01) and erythrocyte ADA
      activity was significantly low (P < 0.01) in BD. Serum ADA activity of active BD
      was higher than that of inactive BD (P < 0.01), but erythrocyte ADA activity was
      found to be lower in active BD than inactive BD (P < 0.01). COMMENT: These
      findings may provide an additional benefit for the diagnosis of BD and sub-typing
      of active and inactive BD.

PMID- 16961546
TI  - Analytic considerations in economic evaluations of multinational cardiovascular
      clinical trials.
AB  - OBJECTIVES: The growing number of economic evaluations that use data collected in
      multinational clinical trials raises numerous questions regarding their execution
      and interpretation. Although recommendations for conducting economic evaluations
      have been widely disseminated, relatively little guidance has been given for
      conducting economic evaluations alongside clinical trials, particularly
      multinational trials. METHODS: Building on a literature review that was conducted
      in preparation for an expert workshop, we evaluated a subset of methodological
      issues related to conducting economic evaluations alongside multinational
      clinical trials. RESULTS: We found wide variation in the types of costs included
      as part of the analyses and in the methods used to assign costs to
      hospitalization events. Furthermore, we found that the extrapolation of costs and
      survival outcomes beyond the trial period is an inconsistent practice and is
      often not dependent on whether a survival benefit was observed in the trial or on
      the epidemiology or practice patterns in the country to which the findings are
      directed. CONCLUSIONS: Although the limited sample size precluded a quantitative
      analysis of trial characteristics and their associations with the methodologies
      employed, our findings highlight the need for more guidance to analysts regarding
      the execution of economic evaluations using data from multinational clinical
      trials. As the research community grapples with the complexities of
      methodological and logistical issues involved in multinational economic
      evaluations, the development of a standardized format to report the basic
      methodological characteristics of such studies would help to improve transparency
      and comparability for other analysts and decision-makers.

PMID- 16961547
TI  - Implantable or external defibrillators for individuals at increased risk of
      cardiac arrest: where cost-effectiveness hits fiscal reality.
AB  - OBJECTIVES: Implantable cardioverter defibrillators (ICDs) are highly effective
      at preventing cardiac arrest, but their availability is limited by high cost.
      Automated external defibrillators (AEDs) are likely to be less effective, but
      also less expensive. We used decision analysis to evaluate the clinical and
      economic trade-offs of AEDs, ICDs, and emergency medical services equipped with
      defibrillators (EMS-D) for reducing cardiac arrest mortality. METHODS: A Markov
      model was developed to compare the cost-effectiveness of three strategies in
      adults meeting entry criteria for the MADIT II Trial: strategy 1, individuals
      experiencing cardiac arrest are treated by EMS-D; strategy 2, individuals
      experiencing cardiac arrest are treated with an in-home AED; and strategy 3,
      individuals receive a prophylactic ICD. The model was then used to quantify the
      aggregate societal benefit of these three strategies under the conditions of a
      constrained federal budget. RESULTS: Compared with EMS-D, in-home AEDs produced a
      gain of 0.05 quality-adjusted life-years (QALYs) at an incremental cost of $5225
      ($104,500 per QALY), while ICDs produced a gain of 0.90 QALYs at a cost of
      $114,660 ($127,400 per QALY). For every $1 million spent on defibrillators, 1.7
      additional QALYs are produced by purchasing AEDs (9.6 QALYs/$million) instead of
      ICDs (7.9 QALYs/$million). Results were most sensitive to defibrillator
      complication rates and effectiveness, defibrillator cost, and adults' risk of
      cardiac arrest. CONCLUSIONS: Both AEDs and ICDs reduce cardiac arrest mortality,
      but AEDs are significantly less expensive and less effective. If financial
      constraints were to lead to rationing of defibrillators, it might be preferable
      to provide more people with a less effective and less expensive intervention (in
      home AEDs) instead of providing fewer people with a more effective and more
      costly intervention (ICDs).

PMID- 16961548
TI  - Eliciting stated preferences for health-technology adoption criteria using paired
      comparisons and recommendation judgments.
AB  - OBJECTIVES: The principal aim of this study was to illustrate applying discrete
      choice methods for eliciting preferences for technology adoption criteria,
      including threshold values for cost-effectiveness ratios. A secondary objective
      was to compare the criteria weights of a sample of industry stakeholders with the
      results obtained from a study of National Institute for Health and Clinical
      Excellence (NICE) recommendations. METHODS: We administered a two-stage stated
      preference (SP) question format to a sample of respondents who have expertise in
      applying economic analysis to technology adoption decisions. We elicited paired
      comparisons and recommendation judgments for similar criteria from a sample of
      International Society for Pharmacoeconomics and Outcomes Research members.
      Respondents evaluated nine pairs of hypothetical drugs, first indicating which
      drug was "better," then indicating what they would recommend to a reimbursement
      authority such as the National Health Service. Stated-choice studies often obtain
      only paired-comparison judgments. RESULTS: Parameter estimates from the initial
      paired-comparison question indicate only incremental cost-effectiveness ratio and
      number of affected patients influence evaluations. These two factors have
      identical weights in the second recommendation question, but all four factors
      were considered in determining the recommendation threshold. Our sample was more
      willing than NICE to accept trade-offs between cost-effectiveness and other drug
      features and was less concerned about cost-effectiveness ratios and information
      uncertainty. Nevertheless, our sample was in agreement with NICE about the
      importance of the number of patients who would benefit as a criterion for
      influencing adoption recommendations. CONCLUSION: This study demonstrates that
      including a question allowing respondents the opportunity to reject both
      alternatives in a forced-choice paired comparison can be important for obtaining
      accurate preference estimates. Our results demonstrate that SP methods offer a
      feasible means of quantifying a broad set of valuations that incorporate the
      preferences of patient, citizen, payer, and other stakeholder groups.

PMID- 16961549
TI  - Development of a Smiling Touchscreen multimedia program for HRQoL assessment in
      subjects with varying levels of literacy.
AB  - OBJECTIVE: As low literacy affects the assessment of health-related quality of
      life (HRQoL) in several ways (e.g., subject eligibility and cost of
      administration), better approaches to HRQoL assessment in subjects with varying
      literacy levels are needed. METHODS: We developed a multimedia touchscreen
      program (the Smiling Touchscreen, ST) to administer HRQoL instruments to subjects
      with varying levels of Chinese language and computer literacy, using an iterative
      process where patients' input on design, clarity of instructions, and user
      friendliness were repeatedly gathered and incorporated in development. The ST
      thus has several user-friendly features for low-literacy subjects (e.g.,
      presentation of individual items using visual and auditory stimuli, voice-text
      synchronization, and visual analog scale with a touch and drag function), which
      we evaluated using qualitative and quantitative methods. RESULTS: The ST was well
      accepted by subjects (n = 66, 76% female, median [interquartile] age: 49.0 [40.0,
      56.0]) with high (n = 43) or low (n = 23) literacy, 98% of whom found it easy or
      very easy to use, and 85% found the voice-text synchronization feature useful. In
      low-literacy subjects without computer experience (30%), none reported any
      difficulties using the ST. The median (interquartile) time spent to complete the
      ST (four Instruction and Practice screens, 24 questions, one visual analog scale)
      for high- and low-literacy groups was 13.9 (9.6, 23.9) and 23.2 (15.8, 26.5)
      minutes, respectively. Among subjects expressing a preference (n = 47), 21 (47%)
      favored the ST over interviewer- or self-administration. CONCLUSION: The ST is
      well accepted by subjects with varying literacy levels, including those without
      computer experience. It is thus a promising new approach for HRQoL assessment
      among subjects with varying literacy levels.

PMID- 16961550
TI  - Validation of the revised 10-item HIV Treatment Satisfaction Questionnaire status
      version and new change version.
AB  - OBJECTIVES: Previous validation of the HIV Treatment Satisfaction Questionnaire
      status version (HIVTSQs) found that nine of the 10 items performed well, but the
      demands item needed revision. This study investigated the psychometric properties
      of the revised HIVTSQs and new change version (HIVTSQc). METHODS: English
      speaking Americans completed the HIVTSQs at baseline and Week 48 of a clinical
      trial of HIV treatments, and the HIVTSQc at Week 48. Demographic and viral load
      information was collected. Psychometric validation used item frequency
      distributions, Confirmatory Factor Analysis (CFA), item-total correlations,
      Cronbach's alpha, Spearman's rank correlation, Kruskal-Wallis and Mann-Whitney
      tests. RESULTS: At baseline, 126 of the 152 patients completed the HIVTSQs fully
      (100 of 106 at Week 48). The negatively skewed distribution of the revised
      demands item resembled that of the other nine, with comparable missing data. CFA
      (baseline and Week 48) supported the general satisfaction/clinical subscale
      (alpha 0.83; 0.85), lifestyle/ease subscale including demands (alpha 0.82; 0.85),
      and 10-item treatment satisfaction scale (alpha 0.89; 0.91). Subscale and scale
      scores differed significantly between ethnic groups. Viral load was not
      significantly related to subscale or scale scores. At Week 48, 97 of 106 patients
      completed the HIVTSQc fully. All items had negatively skewed distributions. CFA
      supported two subscales (general satisfaction/clinical change alpha 0.85;
      lifestyle/ease change alpha 0.88) and 10-item treatment satisfaction change scale
      (alpha 0.92). Viral load change between baseline and Week 48 correlated
      significantly with patients' perceptions of change in HIV control (control(c)
      item), but not with scale or subscale scores. CONCLUSION: The excellent
      psychometric properties of the HIVTSQs and HIVTSQc support their use in clinical
      trials.

PMID- 16961551
TI  - Analyses of cost data in economic evaluations conducted alongside randomized
      controlled trials.
AB  - OBJECTIVE: The adoption and diffusion of new medical treatments depend
      increasingly on evidence of costs and cost-effectiveness. This evidence is
      increasingly being generated from economic data collected in randomized clinical
      trials. The objective of this article is to evaluate the statistical methods used
      for analysis of cost data in economic evaluations conducted alongside randomized
      controlled trials. METHODS: Systematic review of economic evaluations based on
      patient-level cost or resource-use data collected in randomized trials was
      published in 2003. One hundred fifteen articles were identified from the MEDLINE
      database. The use of statistical methods for 1) joint comparison of costs and
      effects and assessment of stochastic uncertainty, 2) incremental cost estimation,
      and 3) handling of incomplete or censored cost data was evaluated. RESULTS: Only
      42 (37%) of the 115 economic evaluations presented a cost-effectiveness ratio or
      estimated net benefits and 24 (57%) of these reported the uncertainty of this
      statistic. A comparison of costs alone was more common with 92 (80%) of the 115
      studies statistically comparing costs between treatment groups. Of these, about
      two-thirds (62; 68%) used at least one statistical test appropriate for drawing
      inferences for arithmetic means. Incomplete cost data were reported in 67 (58%)
      studies with only two using a published statistical approach for handling
      censored cost data. CONCLUSION: The quality of statistical methods used in
      economic evaluations conducted alongside randomized controlled trials was poor in
      the majority of studies published in 2003. Adoption of appropriate statistical
      methods is required before the results from such studies can consistently provide
      valid information to decision-makers.

PMID- 16961552
TI  - A dollar is a dollar is a dollar--or is it?
AB  - It is normally stated that an economic evaluation should take the societal
      perspective and that this implies the incorporation of all costs and effects,
      regardless of where these occur. Nevertheless, this broad perspective may be in
      conflict with the narrower perspective of the health-care decision-makers we are
      usually trying to aid. In this article, it is argued that not all costs have to
      be considered equally important for health-care decision-making and that there is
      a discrepancy between the economically preferred societal perspective and the aim
      of aiding health-care decision-makers. This is related to the concept of local
      rationality. Three reasons why some costs may be considered more important for
      health-care decision-makers than others are: 1) relevance; 2) equity; and 3)
      responsibility. We suggest that it may be useful to adopt a two-perspective
      approach as a standard, presenting one cost-effectiveness ratio following a
      strict health-care perspective and one following the common societal perspective.
      The health-care perspective may assist the health-care policymaker better in
      achieving health-care goals, while the societal perspective indicates whether the
      local rationality of the narrow health-care perspective is also in line with
      societal optimality. More research on actual decisions should provide more
      insight into the relative weights attached to different types of costs.

PMID- 16961553
TI  - Assessing the direct costs of treating nonvalvular atrial fibrillation in the
      United States.
AB  - OBJECTIVE: To determine the health-care resource use and costs attributable to
      treating atrial fibrillation (AF) in the United States. METHODS: Retrospective
      analyses of three federally funded US databases (2001 data): 1) hospital
      inpatient stays (the Healthcare Cost and Utilization Project [HCUP]); 2)
      physician office visits (the National Ambulatory Medical Care Survey [NAMCS]);
      and 3) emergency department (ED) and hospital outpatient department visits (OPD)
      (the National Hospital Ambulatory Medical Care Survey [NHAMCS]). Identification
      of AF medical encounters was based on occurrence of AF-specific International
      Classification of Diseases (9th Edition)--Clinical Modification (ICD-9-CM)
      diagnosis code 427.31 (principal discharge diagnosis for inpatient setting; any
      diagnosis field for other settings). For the 10 most common principal discharge
      diagnoses in the inpatient setting, case-control comparison analyses were
      performed to estimate annual incremental costs of AF as a comorbid discharge
      diagnosis for hospital stays. Regression models were used to assess the impact of
      AF on hospitalization costs. Costs were estimated in year 2005 US dollars.
      RESULTS: Approximately 350,000 hospitalizations, 5.0 million office visits,
      276,000 ED visits, and 234,000 OPD were attributable to AF annually within the
      United States. Total annual costs for treatment of AF were estimated at $6.65
      billion, including $2.93 billion (44%) for hospitalizations with a principal
      discharge diagnosis of AF, $1.95 billion (29%) for the incremental inpatient cost
      of AF as a comorbid diagnosis, $1.53 billion (23%) for outpatient treatment of
      AF, and $235 million (4%) for prescription drugs. In all regressions, AF was a
      significant contributor to hospital cost. CONCLUSIONS: Treatment of AF represents
      a significant health-care burden with the costs of treating AF in the inpatient
      setting outweighing the costs of treating AF in the office, emergency room or
      hospital outpatient settings. Further research is needed to fully capture the
      costs of treating AF.

PMID- 16961554
TI  - Cost-effectiveness of olanzapine as a first-line treatment: a comment.

PMID- 16961557
TI  - Fostering the relationship between environmental health and nursing.

PMID- 16961558
TI  - Geographic information systems: a new tool for environmental health assessments.
AB  - OBJECTIVES: (1) To develop tools for health care professionals and communities to
      assess environmental exposures and (2) to evaluate the utility of integrating
      patient-reported environmental health information with geographic information
      systems (GIS) mapping of environmental data in a pilot study. METHODS: A survey
      was used to collect self-reported environmental exposure and health data from a
      convenience sample of people at an urban community health center (N=101).
      Environmental exposure and census information were obtained from federal
      agencies. Analysis was performed using descriptive statistics and GIS. RESULTS:
      Frequent environmental health risk factors were reported, such as older housing
      (93%) and household smoking (78%). Health problems including asthma (54%) and
      lead poisoning (14%) were reported. Odds ratios indicated a statistically
      significant relationship between mold/mildew and reporting asthma. GIS was found
      to be a useful tool in displaying environmental risk factors and potentially
      associated health effects. CONCLUSIONS: Given the important role that
      environmental health risks can play in public health, it is critical that
      community/public health nurses begin to integrate environmental health assessment
      skills into their professional practices. Simple community surveys can be an
      effective means to raise awareness about environmental health risk factors and
      utilizing GIS can further enhance the accessibility of the combined exposure and
      health information.

PMID- 16961559
TI  - Rural parents' perceptions of risks associated with their children's exposure to
      radon.
AB  - OBJECTIVES: To examine the level of awareness of radon issues, correlates of
      elective testing behaviors, and the accuracy of risk perception for radon
      exposures among rural residents receiving public health services. DESIGN: A cross
      sectional design was used in which questionnaire data and household analytic data
      for radon levels were collected from a nonprobabilistic sample of rural
      households. SAMPLE: Thirty-one rural households with 71 adults and 60 children
      participated in the study. Primary household respondents were female (100%),
      Caucasian (97%), and primarily (94%) between 21 and 40 years of age. MEASUREMENT:
      Questionnaire data consisted of knowledge and risk perception items about radon
      and all homes were tested for the presence of radon. RESULTS: The prevalence of
      high airborne radon (defined as> or=4 pCi/l) was 32%. More than a third of the
      sample underestimated the seriousness of health effects of radon exposure, 39%
      disagreed that being around less radon would improve the long-term health of
      their children, and 52% were unsure whether radon could cause health problems.
      After adjusting for chance, only 21% of the subjects correctly understood their
      risk status. CONCLUSIONS: This study provides preliminary evidence that low
      income rural citizens do not understand their risk of radon exposure or the
      deleterious consequences of exposure.

PMID- 16961560
TI  - Evaluation of a multistate faith-based program for children affected by natural
      disaster.
AB  - OBJECTIVES: To systematically evaluate Camp Noah, a faith-based intervention for
      children affected by natural disaster: to assess the extent to which the camps
      were carried out according to the program design, to describe how the Camp Noah
      program was implemented, and to explore Camp Noah program effects on children.
      DESIGN: Qualitative survey. SAMPLE: Twenty-eight local, state, and national
      stakeholders. MEASUREMENT: Open-ended interviews. RESULTS: Although camps adhered
      to the curriculum, many implementation weaknesses resulted from a lack of clear
      program structure and written procedures. Stakeholders observed that children
      generally were able to process their disaster experiences in the camp, and some
      children exhibited increased understanding of God's role in their disaster
      experience. Stakeholders also described parent reports of increased coping skills
      related to weather among some children. Lastly, stakeholders both observed
      positive effects of Camp Noah on children's behaviors and symptoms and described
      changes reported to them by parents. CONCLUSIONS: Every year, thousands of
      children suffer emotionally as a result of natural disaster in the United States.
      With public health nursing support and improvements in infrastructure, Camp Noah
      may be a promising intervention to address this important public health problem.

PMID- 16961561
TI  - Using a site visit to a contaminated location as a focus for environmental health
      education for academic and public health nurses.
AB  - We describe a conference initiative that is distinguished by the use of a
      "community case study" to increase the knowledge and skills of nursing faculty
      and public health nurses in environmental health and to provide networking
      support to facilitate infusion of environmental health into nursing curricula and
      public health nursing practice. The Institute of Medicine's (1995) general
      environmental health competencies for nurses provided the conference framework.
      Woburn, Massachusetts, a Superfund site, served as the community case study to
      illustrate a complex environmental health problem. Over an extended period of
      time, Woburn was contaminated with multiple chemicals that eventually
      contaminated the drinking water supply; a cluster of childhood leukemia cases was
      linked subsequently to the Superfund site contaminants. A 6-hr interpreted
      walking and bus tour of the Superfund site enabled us to visit the premises of
      responsible parties, the vapor extraction fields, the capped Well H in the wooded
      wetlands, and to tour the affected neighborhood. This intensive, hands-on
      approach to learning environmental health content and skills that incorporated
      multiple learning strategies serves as a model for developing future conferences
      for public health nurses and nursing faculty.

PMID- 16961562
TI  - Open the door whenever opportunity knocks.
AB  - The Community Environmental Health Program/Community Outreach and Education
      Program (CEHP/COEP) New Mexico Center for Environmental Health Sciences has
      learned that listening and responding to opportunities that arise in local
      communities can be a more effective means of reaching health care providers, lay
      health workers, and community members than structured plans of action. While
      specific opportunities that have occurred in New Mexico may be unique, they are
      presented here with the hope that they might suggest new strategies to the reader
      and help to identify parallel opportunities in other communities. The paper is
      organized around three major opportunities to which CEHP/COEP has responded: (1)
      the need for more informed health care in communities with unique and complex
      environmental and occupational exposures due to their proximity to National
      Laboratories; (2) the need for resources on environmental health within local
      provider networks and issue-specific groups; and (3) the need for community
      environmental health projects within the College of Nursing. CEHP/COEP's
      responses, observations, and lessons learned through these experiences are
      discussed. In the end, the major lesson is that the ability to respond to
      opportunities requires flexibility and creativity; by sticking doggedly to plans,
      valuable-and sometimes more profitable and productive-opportunities may be
      missed.

PMID- 16961563
TI  - Incorporating a built environment module into an accelerated second-degree
      community health nursing course.
AB  - Environmental quality is a leading indicator of population health. Environmental
      health content has been integrated into the curriculum of an Accelerated Bachelor
      of Science in Nursing program for second-degree students through development of
      an environmental health nursing module for the final-semester community health
      nursing course. The module was developed through collaboration between two
      professional schools at Duke University (the School of Nursing and the Nicholas
      School of the Environment and Earth Sciences). It focused on the role of the
      built environment in community health and featured a mix of teaching strategies,
      including five components: (1) classroom lecture with associated readings, (2)
      two rounds of online small-group student discussions, (3) assessment of the built
      environment in local neighborhoods by student teams, (4) team presentation of the
      neighborhood assessments, and (5) individual student papers synthesizing the
      conclusions from all team presentations. The goal of the module was to provide
      nursing students with an organizing framework for integrating environmental
      health into clinical practice and an innovative tool for understanding community
      level components of public health.

PMID- 16961564
TI  - Challenges and successes of infusing environmental health content in a nursing
      program.
AB  - Environmental health has received minimal attention in nursing curricula over the
      past decade, despite efforts by the Institute of Medicine (1995) and others to
      advance the environmental health agenda in nursing education, practice, and
      research. This paper describes an initiative that was first funded as a part of
      the Environmental Health Scholars Program in 2000 to incorporate environmental
      health into master's and undergraduate nursing programs at one university.
      Evaluation of this initiative highlights the challenges and successes experienced
      in this academic setting. A number of recommendations based on this experience
      and the literature are offered. There is a perceived need to define the critical
      body of knowledge and skills in environmental health and to develop tools to
      enable educators and practitioners to apply this knowledge in public health
      nursing and other specialty practices. In tandem, opportunities and incentives
      are needed to encourage faculty development and the infusion of environmental
      health into existing curricula. Changes are also needed across practice settings
      to proactively address environmental health issues so that environmental health
      becomes and remains an integral part of nursing.

PMID- 16961565
TI  - Does Dixon's Integrative Environmental Health Model inform an understanding of
      rural parents' perceptions of local environmental health risks?
AB  - A qualitative study of parents' perceptions of local environmental health risks
      was conducted to assess the fit between concepts from Dixon's Integrative
      Environmental Health Model (DIEH model) and field-generated data. This research
      was part of a prospective study addressing environmental exposures of rural low
      income children. Home visit data from 11 parents were analyzed (1) thematically
      and (2) according to DIEH concepts. These complementary analyses allowed the
      researchers to examine perceptions that were congruent with or diverged from the
      DIEH model. Findings revealed that participants were concerned about children's
      exposure to pathogenic molds and cigarette smoke and felt uninformed about risks
      and prevention strategies. Barriers to preventive actions included families' lack
      of time and a disinterest in brochures. Participants reported being "stuck" in
      substandard housing by poverty and family demands. They expressed concern about
      risks, but were unsure "what to worry about." Results provided the researchers
      with confidence that the DIEH model aligned with participants' cognitive
      constructions of risk. As a result, the DIEH model was incorporated into the
      conceptualization for the clinical trial phase of the study. This type of check
      between a theoretical approach and field data can be a helpful intermediate step
      for researchers involved in multiyear studies.

PMID- 16961567
TI  - The Spanish influenza of 1918 in St. Louis, Missouri.
AB  - In view of current concern about a possible pandemic of virulent avian influenza,
      it is timely to revisit the public health response to the "Spanish" influenza of
      1918. St. Louis, Missouri, was the most successful of nine largest cities in
      limiting the death toll from influenza and pneumonia through the use of public
      health measures during the first 8 weeks of the epidemic. A second wave of cases
      increased the final death rate, but it remained below that of other major cities.
      Public health officials attributed the lower death rate to the early and rigorous
      ban on public gatherings.

PMID- 16961566
TI  - A case study in the use of community-based participatory research in public
      health nursing.
AB  - There is growing demand for research using a community-based participatory (CBPR)
      approach. CBPR requires that the academic research team actively partner with
      community members and stakeholders in the entire research process. The community
      members are full partners with the researchers in relation to the development and
      implementation of the study, analysis of the data, and dissemination of the
      findings. The purpose of this article is to review four basic principles of CBPR
      and provide an example of how these CBPR principles were used in an ethnographic
      study related to the culture of African American infant health. In the pilot
      study, CBPR provided the framework for recruitment and retention of participants,
      ongoing data analysis, and dissemination of findings. Using CBPR provided the
      researchers an introduction into the selected community. Community members served
      as key informants about the culture of the community and provided access to
      potential participants. The community partners contributed to analysis of
      emerging themes and in the dissemination of findings to the community,
      stakeholders, and the scientific community. CBPR provides opportunities for
      community health nurse researchers to conduct research with vulnerable
      populations and sets the stage for implementing evidenced-based nursing
      interventions in the community.

PMID- 16961568
TI  - Diazepam administration prevents testosterone decrease and lipofuscin
      accumulation in testis of mouse exposed to chronic noise stress.
AB  - Lipofuscin is an autofluorescent and undegradable material, which accumulates in
      tissues during ageing and under different types of stress. Among these, oxidative
      stress represents a major trigger for lipofuscin formation. However, prolonged
      noise exposure is also an effective stressful stimuli. Diazepam may inhibit
      lipofuscinogenesis in liver and prevent the noise-induced reduction of the
      steroidogenesis in the adrenal gland. The aim of the study was to ascertain
      whether chronic noise exposure causes lipofuscin accumulation in mouse testis,
      and to evaluate the effects of diazepam administration. Eight-week old mice were
      either exposed for 6 weeks (6 h day(-1)) to white-noise (group A), or received
      diazepam (3 mg kg(-1), i.p.) before noise exposures (group B), while a further
      group was used as control (group C). Light fluorescence and transmission electron
      microscopy revealed lipofuscin in large amounts in the Leydig cells in mice of
      group A, which concomitantly had low serum testosterone levels; pre-treatment
      with diazepam occluded both effects. The present study indicates that: (i)
      chronic noise exposure causes lipofuscin accumulation at the level of the Leydig
      cells and a decrease in testosterone; (ii) all these effects are suppressed by
      pre-treatment with diazepam. As the Leydig cells represent the only cellular type
      of the interstitial testicular tissue having peripheral benzodiazepine receptors,
      these results could be explained by the capacity of the peripheral benzodiazepine
      receptors to prevent reactive oxygen species damage and to increase the
      resistance of these cells to oxidative stress.

PMID- 16961569
TI  - Effect of Black maca (Lepidium meyenii) on one spermatogenic cycle in rats.
AB  - Lepidium meyenii (Maca) grows exclusively between 4000 and 4500 m above sea level
      in the Peruvian central Andes. The hypocotyls of this plant are traditionally
      used in the Andean region for their supposed fertility-enhancing properties. The
      hypocotyls have different colours. Of these, Black maca has better effects on
      spermatogenesis. The present study aimed to test the hypothesis that Black maca
      has early effects during a spermatogenic cycle (12 days) of male rats. For this,
      testicular spermatid, epididymal sperm and vas deferens sperm counts were
      measured after 1, 3, 5, 7 and 12 days of treatment with Black maca. Aqueous
      extract of Black maca was given orally by daily gavage at a dose of 2 g kg(-1).
      In a spermatogenic cycle, compared with day 1, daily sperm production (DSP) was
      lower at day 7 (control), whereas with Black maca, the difference was observed at
      day 12. Epididymal sperm count was higher in rats treated with Black maca at days
      1, 3 and 7, but similar to controls at days 5 and 12; similarly sperm counts in
      vas deferens was higher in rats treated with Black maca in days 3, 5 and 7, but
      similar to controls at days 1 and 12. From this, it is suggested that first
      action of Black maca was at epididymal level increasing sperm count after 1 day
      of treatment, whereas an increase in sperm count was observed in vas deferens at
      day 3 of treatment. Finally, an increase in DSP was observed after 7 days of
      treatment with Black maca. Testicular testosterone was not affected after 7 days
      treatment with Black maca. In conclusion, Black maca affects sperm count as early
      as 1 day after beginning of treatment.

PMID- 16961570
TI  - Decreased polyunsaturated and increased saturated fatty acid concentration in
      spermatozoa from asthenozoospermic males as compared with normozoospermic males.
AB  - The lipid composition of the sperm membrane has been shown to exert a significant
      effect upon the functional quality of spermatozoa. We have studied fatty acid
      composition of the phospholipids in spermatozoa in asthenozoospermic and
      normozoospermic men and determined the ratio of polyunsaturated fatty acids
      (PUFAs) to saturated fatty acids of spermatozoa of these two groups. Fatty acid
      concentration of spermatozoa was determined in 15 asthenozoospermic and eight
      normozoospermic semen samples by thin layer chromatography and gas
      chromatography. The most abundant polyunsaturated and saturated fatty acids in
      normozoospermic samples were docosahexaenoic acid (DHA 22 : 6 omega3, 98.5 +/-
      4.5 nmol per 10(8) spermatozoa, mean +/- SE) and palmitic acid (103 +/- 17 nmol
      per 10(8) spermatozoa) respectively. The mean +/- SE values of DHA and palmitic
      acid in asthenozoospermic samples were 53.9 +/- 11.6 and 145 +/- 14.7 nmol per
      10(8) spermatozoa respectively. Compared with normozoospermic samples,
      asthenozoospermic samples showed lower levels of PUFA and higher amount of
      saturated fatty acids. The mean +/- SE ratios of sperm PUFA/saturated fatty acids
      in asthenozoospermic and normozoospermic samples were 0.66 +/- 0.06 and 1.45 +/-
      0.16 (P < 0.001) respectively. This study demonstrates that spermatozoa of
      asthenozoospermic men have lower levels of PUFA compared with saturated fatty
      acids. This may be contributory to the poor motility noted in samples from these
      men.

PMID- 16961571
TI  - The role of paternal chromosomes and sperm morphology on the outcome of
      intracytoplasmic sperm injection.
AB  - The study investigated the possible relationship between the X/Y chromosomes
      bearing spermatozoa and the outcome of intracytoplasmic sperm injection (ICSI)
      therapy and morphological appearance/shape (Tygerberg criteria) of the sperm cell
      injected into the oocyte during ICSI therapy and fertilisation. Thirty-nine
      patients were recruited for the study from an assisted reproductive programme.
      Semen samples were prepared by using gradient centrifugation techniques. Prior to
      injection sperm images were captured using high-quality video graphic equipment.
      Sperm selection was based on the concept of 'best-looking' spermatozoa i.e.
      spermatozoa lacking gross and obvious malformations such as broken necks,
      cytoplasmic droplets, amorphous or elongated heads. Photomicrographs of each
      sperm cell were produced from video footage. The photographical material was used
      to determine the basic shape and the actual length-to-width ratio of the injected
      sperm heads. Embryo biopsies and fluorescent in situ hybridisation (FISH) was
      performed on 12 randomly selected couples from a set of 39. Embryos were
      evaluated on day 3 for development and embryo transfer. Embryo biopsies and FISH
      analyses were performed on those embryos that showed no developmental potential
      following injection. It was found that 70% of the embryos that showed no
      developmental potential were Y chromosome-bearing embryos. The sperm selection
      process for ICSI based on the approach of choosing the 'best-looking'
      spermatozoon in the ejaculate seems to provide cells that can be classified as
      normal based on the length-to-width ratio set by the World Health Organization
      for normal cells.

PMID- 16961572
TI  - Effects of exposure of pre-pubertal boars to di(2-ethylhexyl) phthalate on their
      frozen-thawed sperm viability post-puberty.
AB  - Late effects of pre-pubertal oral exposure to di(2-ethylhexyl) phthalate (DEHP),
      a plastic softener used in, for example, polyvinyl chloride-products, on semen
      quality in young boars have not been clear-cut. The aim of this study was to
      determine whether stress imposed on spermatozoa would reveal such effects. Semen
      was collected from post-pubertal boars (8-9 months of age), which had been
      exposed to 300 mg kg(-1) body weight of DEHP per os three times a week from 3 to
      7 weeks of age and from control siblings given placebo (water). The semen was
      cryopreserved and examined for plasma membrane integrity post-thaw using the
      short hypo-osmotic swelling test and flow cytometry (propidium iodide /SYBR-14).
      Sperm motility was assessed by computer-assisted sperm analysis. No significant
      difference in plasma membrane integrity could be found between the groups. The
      DEHP-exposed group had a significantly lower percentage of linearly motile
      spermatozoa at 30 min (P < 0.05) and 120 min (P < 0.001) after thawing, and a
      larger amplitude of lateral displacement of the head 120 min after thawing (P <
      0.05), compared with controls. In summary, spermatozoa from boars pre-pubertally
      exposed to low doses of DEHP, showed kinematic deviations post-thaw that could be
      related to DEHP exposure.

PMID- 16961573
TI  - Testicular venous sampling in determining the possible origin of tumour markers
      and its influence on management.
AB  - Testicular vein sampling is a well-known technique in the investigation of
      testicular function, or in determining the origin of certain plasma protein
      markers. We describe the application of this technique in the case of a patient
      who had previously undergone right radical orchidectomy for testicular teratoma,
      to discover the source of persistently raised tumour markers following the
      operation. We found this diagnostic tool useful in avoiding unnecessary
      procedures of the remaining testis and in guiding further treatment.

PMID- 16961575
TI  - A new, broad-spectrum azole antifungal: posaconazole--mechanisms of action and
      resistance, spectrum of activity.
AB  - Posaconazole, a new triazole antifungal, exerts principally the same mechanism of
      action as the other azole derivatives, i.e. it inhibits the ergosterol production
      by binding and inhibiting the lanosterol-14alpha-demethylase which is present in
      almost all fungi except Pneumocystis and Pythium. Posaconazole has an exquisitely
      high affinity to this target. Since posaconazole has a chemical structure
      different from fluconazole and voriconazole, it can interact with an additional
      domain of the target so that it may inhibit even mutated strains resistant to
      fluconazole and voriconazole. In addition posaconazole is a bad substrate for
      efflux pumps in fungi, so it can stay active when other azoles are already
      inactive. Furthermore, the spectrum of posaconazole is rather large including
      also some zygomycetes resistant to other azoles. In conclusion, posaconazole is
      actually the most potent azole derivative used in medicine. A combination of
      posaconazole with other groups of antifungals may have a favourable effect. There
      are several methods to test the in vitro activities of posaconazole including the
      E-test, though interpretive breakpoints are still lacking.

PMID- 16961576
TI  - Antifungal efficacy and pharmacodynamics of posaconazole in experimental models
      of invasive fungal infections.
AB  - Posaconazole is a novel lipophilic antifungal triazole with potent and broad
      spectrum activity against opportunistic, endemic and dermatophytic fungi. This
      activity extends to organisms that are often refractory to existing triazoles,
      amphotericin B or echinocandins such as Candida glabrata, Candida krusei,
      Aspergillus terreus, Fusarium spp. and the Zygomycetes. A large number of
      experimental animal models of invasive fungal infections has demonstrated the
      potent and broad-spectrum efficacy of posaconazole in vivo, both in normal and in
      immunocompromised animals. Consistent with these preclinical data, posaconazole
      showed strong a antifungal efficacy in phase II and phase III clinical trials in
      immunocompromised patients with oropharyngeal and oesophageal candidiasis and as
      salvage therapy in patients with invasive fungal infections, and was effective as
      antifungal prophylaxis in high-risk patients. This paper reviews the preclinical
      disposition, antifungal efficacy and pharmacodynamics of posaconazole in and its
      implications for treatment and prevention of invasive fungal infections.

PMID- 16961577
TI  - HPLC analysis of the antifungal agent posaconazole in patients with
      haematological diseases.
AB  - Posaconazole is a new antifungal drug used in prophylaxis and therapy of fungal
      infections in patients with immunodeficiency. In the clinical development,
      posaconazole exhibits variable oral bioavailability. Hence drug monitoring is
      recommended. For this purpose, a rapid and a convenient high-performance liquid
      chromatography (HPLC) method has been developed. To 200 mul serum, 50 mul
      internal standard (itraconazole) was added. After precipitation of the proteins
      with acetonitrile, the clear supernatant was evaporated in a centrifugal
      evaporator, and the residue was dissolved in the HPLC elution. Separation was
      done on a chromatography performed by injecting a 50 mul aliquot of the
      resuspended sample onto a Multohyp C18 BDS column (250 x 4 mm). Column
      temperature was maintained at 50 degrees C. The flow rate was 1 ml min(-1).
      Retention time of posaconazole was about 9 min and those of itraconazole was 17
      min. The limit of quantification was 50 mug l(-1) and the limit of detection
      about 10 mug l(-1). Until now the concentration of posaconazole was measured in
      14 patients (64 samples). After a daily dosage of 600-800 mg posaconazole the
      serum concentrations varied between 100 and 3000 mug l(-1) (582 +/- 579 mug l(
      1)). Oral bioavailability was especially low in patients with cytostatic therapy
      and/or bone marrow transplantation. Further studies are needed to establish the
      therapeutic range of the posaconazole concentrations.

PMID- 16961578
TI  - Second-line treatment in invasive mould infections.
AB  - A prevalence of up to 30% of invasive fungal infections (IFI) has been reported
      from autopsy studies in patients treated for haematological malignancies. Despite
      substantial advances in the last decade, IFI are still associated with a
      mortality of up to more than 70%, in particular for those patients suffering from
      invasive aspergillosis. Some progress has been made in diagnostics with the
      advent of new non-culture based tools and the improvement of imaging techniques.
      However, the response rates are about 40-60% in the first-line treatment of IFI.
      Salvage therapy will be necessary for those being intolerant or refractory
      towards the respective first-line antifungal. Following a long period of
      stagnation, there has been a considerable progress during the last five years in
      the treatment of refractory IFI. This review highlights the new treatment options
      for the salvage setting in the context of the state-of-the-art management of IFI
      in cancer patients.

PMID- 16961579
TI  - Successful treatment of disseminated mucormycosis with a combination of liposomal
      amphotericin B and posaconazole in a patient with acute myeloid leukaemia.
AB  - The combination of resection of infected tissue and antifungal therapy is the
      treatment of choice in mucormycosis. In disseminated mucormycosis, where surgery
      is impossible, the mortality is almost 90%. We report the first case of
      disseminated mucormycosis that was cured with a combination therapy of liposomal
      amphotericin B and posaconazole without surgical intervention.

PMID- 16961580
TI  - Rhinocerebral zygomycosis in a young girl undergoing allogeneic stem cell
      transplantation for severe aplastic anaemia.
AB  - We report on a 10-year-old girl with severe aplastic anaemia who developed
      rhinocerebral infection caused by Absidia corymbifera and a possible co-infection
      caused by Alternaria alternata. Despite prolonged neutropenia, therapy with
      liposomal amphotericin B and posaconazole improved the clinical condition.
      Subsequently, the girl underwent allogeneic haematopoietic stem cell
      transplantation (HSCT) for the underlying disease, but the fungal infection
      remained under control with the antifungal treatment. No severe side effect of
      the antifungal drugs was noted. Unfortunately, the girl died 5 months after HSCT
      due to disseminated adenovirus infection.

PMID- 16961581
TI  - Posaconazole for treatment of refractory invasive fungal disease.
AB  - Invasive fungal infections are usually associated with immunocompromised states
      About 40-60% of these patients are refractory to standard antifungal therapy We
      describe the effect of posaconazole in the treatment of a 12 years-old girl with
      uncontrolled diabetes mellitus with life-threatening cerebral mucor mycosis and a
      4 year old girl boy with chronic granulomatous disease presenting with invasive
      Aspergillus nidulans infection.

PMID- 16961582
TI  - Salvage therapy of refractory chronic disseminated candidiasis in a patient with
      acute myeloid leukaemia and secondary prophylaxis during allogeneic stem cell
      transplantation.
AB  - We report on the treatment course of a 27-year-old male patient with acute
      myeloid leukaemia M1 and chronic disseminated candidiasis. After induction
      chemotherapy, the patient developed oesophageal candidiasis while participating
      in a voriconazole vs. placebo prophylaxis trial. He was then switched to oral
      fluconazole 400 mg q.i.d. After 6 days of futile fluconazole therapy he was
      switched to caspofungin 50 mg q.i.d. Caspofungin dose was later increased to 100
      mg q.i.d after disseminated candidiasis with involvement of lung, spleen and
      liver was diagnosed. Following 63 days of caspofungin without resolution of
      symptoms, i.e. being persistently febrile, and emergence of soft tissue Candida
      abscesses, he was included into a trial allowing compassionate use of
      posaconazole as salvage therapy for refractory invasive fungal infections.
      Symptoms rapidly resolved under posaconazole 200 mg q.i.d. treatment and the
      patient was able to undergo allogeneic haematopoietic stem cell transplantation
      on secondary prophylaxis with posaconazole.

PMID- 16961583
TI  - A novel missense mutation responsible for factor VII deficiency in research
      Beagle colonies.
AB  - BACKGROUND: Canine factor VII (cFVII) deficiency, an autosomal recessive trait
      originally identified in research Beagles, is associated with a mild to moderate
      bleeding tendency. OBJECTIVE: Our aim was to identify and characterize the
      mutation causing cFVII deficiency. METHODS: In order to sequence the coding
      regions of the cFVII gene, we cloned the cFVII cDNA. Genomic DNA and plasma from
      FVII-deficient Beagles and obligate carriers were utilized. RESULTS: In all FVII
      deficient dogs, we identified a single causative G to A missense mutation in exon
      5, encoding the second epidermal growth factor-like domain, resulting in
      substitution of glycine 96 by glutamic acid, with plasma FVII coagulant activity
      of <or = 4% in affected Beagles. In vitro expression indicated that the majority
      (96%) of cFVII-G96E protein was retained intracellularly. In addition, analysis
      of purified recombinant wild-type and mutant cFVII proteins demonstrated reduced
      activity of the mutant (< 2%) compared with wild-type. Rotational
      thromboelastometry revealed a severe impairment of clotting activity in affected
      Beagles, and heterozygotes also exhibited changes in coagulation-based assays.
      Using a mutation-specific polymerase chain reaction/restriction digest that
      allows rapid identification of the G96E mutation, we surveyed a US research
      Beagle colony and identified a mutant allelic frequency of 31%. CONCLUSIONS: We
      have identified a single causative mutation for cFVII deficiency that may have
      implications for pharmacotoxicologic research, because reduced FVII coagulant
      activity may alter hemostatic and/or cardiovascular endpoints in this commonly
      used animal species.

PMID- 16961584
TI  - The potential role of antiplatelet agents in modulating inflammatory markers in
      atherothrombosis.
AB  - Atherothrombosis is the process that links atherosclerotic lesion development
      with unpredictable and life-threatening ischemic vascular events such as angina,
      myocardial infarction, transient ischemic attack, and stroke. Atherothrombosis is
      triggered when an unstable atherosclerotic lesion is ruptured, leading to
      platelet activation and thrombus formation. Inflammatory mediators are
      responsible for lesion instability leading to rupture, and in recent years
      atherothrombosis and its underlying condition of atherosclerosis have come to be
      recognized as manifestations of inflammatory disease. Inflammatory mediators may
      therefore serve as early markers of atherothrombosis. Measurement of early
      markers may be used to predict future ischemic events and improve risk
      stratification in patients following diagnosis of atherothrombotic disease. In
      addition, detection of such markers may help to optimize the use of current
      therapies to manage atherothrombosis. Molecules that may serve as early markers
      of atherothrombotic disease include C-reactive protein, CD40 ligand,
      myeloperoxidase, pregnancy-associated plasma protein and plasminogen activator
      inhibitor-1. Early indications are that levels of these markers are influenced by
      therapies currently in use in the treatment of atherothrombotic conditions,
      including antiplatelet agents. Ongoing studies will provide further insight into
      routine assessment of inflammatory markers as a guide to the management of
      patients with atherothrombosis.

PMID- 16961585
TI  - Thrombin-triggered platelet apoptosis.
AB  - BACKGROUND: Thrombin is primarily known as a coagulation factor and as an inducer
      of platelet activation and aggregation. It has been reported that thrombin
      modulates apoptosis of nucleated cells. OBJECTIVES: The current study
      investigated whether thrombin can affect apoptosis in anucleated human platelets.
      METHODS: Using flow cytometry, we studied platelet apoptosis at the single-cell
      level, analyzing markers of mitochondrial and cytoplasmic apoptosis. Western
      blotting was also employed, in addition to flow cytometry, for determining the
      expression of Bcl-2 family proteins. RESULTS: We found that human alpha-thrombin
      induced four key manifestations of apoptosis in human platelets: (i)
      mitochondrial inner transmembrane potential (DeltaPsi m) depolarization; (ii)
      strong expression of pro-apoptotic Bax and Bak proteins but only weak expression
      of anti-apoptotic Bcl-2 protein; (iii) caspase-3 activation; and (iv)
      phosphatidylserine (PS) exposure. CONCLUSIONS: This study demonstrates that,
      aside from its 'classical' function as an inducer of platelet activation,
      thrombin can trigger platelet apoptosis, where it acts as a death ligand. These
      data indicate that thrombin triggers platelet apoptosis by impacting on several
      intracellular apoptotic targets, including shifting the balance between Bcl-2
      regulatory proteins in a pro-apoptotic direction, depolarizing the inner
      mitochondrial membrane, activating the executioner caspase-3, and stimulating
      aberrant exposure of PS on the platelet surface.

PMID- 16961587
TI  - Abstracts of Australian Gastroenterology Week. October 11-14, 2006. Adelaide,
      South Australia, Australia.

PMID- 16961586
TI  - Prothrombotic factors enhance heparin-induced thrombocytopenia and thrombosis in
      vivo in a mouse model.
AB  - BACKGROUND: Heparin-induced thrombocytopenia/thrombosis (HIT/T) is a common cause
      of life- and limb-threatening thrombosis. The development of antibodies that
      react with complexes of heparin and platelet factor 4 (PF4) is fundamental to the
      development of the disease. However, anti-PF4/heparin antibodies are far more
      common than is HIT/T and there is less understanding of the factors that
      contribute to thrombosis in only a subset of patients. OBJECTIVES: Both
      qualitative and quantitative differences in multiple factors (e.g. antibodies,
      heparin and platelets) may influence the clinical course of patients who develop
      anti-PF4/heparin antibodies. We examined the hypothesis that host-specific
      factors, such as comorbid prothrombotic conditions, would exacerbate the
      pathologic effects of anti-PF4/heparin antibodies. METHODS AND RESULTS: A mouse
      model transgenic for human Fcgamma RIIa and PF4 and null for mouse PF4 was used
      to study the influence of prothrombotic conditions on the effects of anti
      PF4/heparin antibodies in vivo. To simulate a prothrombotic milieu, mice were fed
      a hypercholesterolemic diet (HD). HD-fed mice had elevated plasma cholesterol,
      increased platelet reactivity and increased endothelial activation relative to
      mice fed a standard diet (SD). Age- and sex-matched mice from each diet group
      were treated with an anti-PF4/heparin antibody and heparin. HD-fed mice developed
      more severe thrombocytopenia than similarly treated SD-fed mice. Mice with
      moderate to severe thrombocytopenia had elevated plasma levels of thrombin
      antithrombin complexes, indicative of increased thrombin generation in vivo.
      Platelet-fibrin thrombi were observed in multiple organs of HD-fed mice that
      developed severe thrombocytopenia. CONCLUSIONS: Host-specific factors, such as
      prothrombotic changes in platelet reactivity and/or endothelial activation, may
      influence the development of thrombosis in a subset of patients who develop anti
      PF4/heparin antibodies.

PMID- 16961588
TI  - Mi-2 chromatin remodeling factor functions in sensory organ development through
      proneural gene repression in Drosophila.
AB  - Mi-2, the central component of the nucleosome remodeling and histone
      deacetylation (NuRD) complex, is known as an SNF2-type ATP-dependent nucleosome
      remodeling factor. No morphological mutant phenotype of Drosophila Mi-2 (dMi-2)
      had been reported previously; however, we found that rare escapers develop into
      adult flies showing an extra bristle phenotype. The dMi-2 enhanced the phenotype
      of ac(Hw49c), which is a dominant gain-of-function allele of achaete (ac) and
      produces extra bristles. Consistent with these observations, the ac-expressing
      proneural clusters were expanded, and extra sensory organ precursors (SOP) were
      formed in the dMi-2 mutant wing discs. Immunostaining of polytene chromosomes
      showed that dMi-2 binds to the ac locus, and dMi-2 and acetylated hisotones
      distribute on polytene chromosomes in a mutually exclusive manner. The chromatin
      immunoprecipitation assay of the wing imaginal disc also demonstrated a binding
      of dMi-2 on the ac locus. These results suggest that the Drosophila Mi-2/NuRD
      complex functions in neuronal differentiation through the repression of proneural
      gene expression by chromatin remodeling and histone deacetylation.

PMID- 16961589
TI  - Programmed cell death of the ovarian nurse cells during oogenesis of the silkmoth
      Bombyx mori.
AB  - In the present study, we describe the features of programmed cell death of the
      ovarian nurse cells occurring during vitellogenesis of the silkmoth Bombyx mori.
      At developmental stage 5, the nurse cells occupy one-half of the follicular
      volume and obtain a rather spherical shape, while the nurse cell nuclei appear
      large and elongated, forming impressive projections. At the following stage,
      stage 6, the nurse cells decrease in size and their shape becomes elliptic. The
      nuclei remain elongated, being also characterized by large lobes. The lobes of
      the ramified nurse cell nuclei seem to retain the nucleus in the center of the
      cell during the dumping of the nurse cell cytoplasm into the growing oocyte. At
      stage 7, membrane enclosed vacuoles can be easily detected into the nurse cells
      cytoplasm. Ultrastructural analysis and fluorescent microscopy using mono-dansyl
      cadaverine staining of these vacuoles also reveal that they represent
      autolysosomes. Caspase activity is detected during stage 7, as it is demonstrated
      by using the Red-VAD-FMK staining reagent. At developmental stages 8 and 9, the
      nurse cells exhibit chromatin condensation, DNA fragmentation and caspase
      activity. Finally, during the following stage 10, the nuclear remnants are
      assembled into apoptotic vesicles, which, after being phagocytosed, are observed
      in the cytoplasm of adjacent follicle cells. We propose that apoptosis and
      autophagy operate synergistically during vitellogenesis of B. mori, in order to
      achieve an efficient and rapid clearance of the degenerated nurse cell cluster.

PMID- 16961590
TI  - Role of Gbx2 and Otx2 in the formation of cochlear ganglion and endolymphatic
      duct.
AB  - The boundary of gene expression of transcription factors often plays a role in
      making a signaling center in development. In the otic vesicle, Gbx2 is expressed
      in the dorso-medial region including the endolymphatic duct, and Otx2 in the
      ventral region. Fgf10 is expressed between their expression boundaries, and the
      cochleovestibular ganglion develops close to the medial side of the Fgf10
      expressing domain. Similar expression patterns are observed in the central
      nervous system, where Otx2 and Gbx2 expression abut at the mid-hindbrain
      boundary, and the repressive interaction between Otx2 and Gbx2 defines the mid
      hindbrain boundary. These analogous expression patterns raise a question about
      the role of the interaction between Gbx2 and Otx2 in the otic vesicle. To address
      this, we misexpressed Gbx2 and Otx2 to the otic epithelium. Ectopic Gbx2
      expression could repress Otx2 expression and vice versa. In addition, Fgf10
      expression was repressed and cochlear ganglion formation was interfered with.
      Moreover, endolymphatic duct was severely hypomorphic in the Otx2 misexpressing
      embryos. These results suggest that the interaction between Gbx2 and Otx2 in
      developing inner ear defines Fgf10 expression domain to induce the cochlear
      ganglion. It is also suggested that Gbx2 expression is important for the
      formation of the endolymphatic duct.

PMID- 16961591
TI  - Role of hunchback in segment patterning of Locusta migratoria manilensis revealed
      by parental RNAi.
AB  - In long germ embryos, all body segments are specified simultaneously during the
      blastoderm stage. In contrast, in short germ embryos, only the anterior segments
      are specified during the blastoderm stage, leaving the rest of the body plan to
      be specified later. The striking embryological differences between short and long
      germ segmentation imply fundamental differences in patterning at the molecular
      level. To gain insights into the segmentation mechanisms of short germ insects,
      we have investigated the role of the homologue of the Drosophila gap gene
      hunchback (hb) in a short germ insect Locusta migratoria manilensi by paternal
      RNA interference (RNAi). Phenotypes resulting from hb knockdown were categorized
      into three classes based on severity. In the most extreme case, embryos developed
      the most anterior structures only, including the labrum, antennae and eyes. The
      following conclusions were drawn: (i) L. migratoria manilensis hb (Lmm'hb)
      controls germ band morphogenesis and segmentation in the anterior region; (ii)
      Lmm'hb may function as a gap gene in a wide domain including the entire gnathum
      and thorax; and (iii) Lmm'hb is required for proper growth of the posterior germ
      band. These findings suggest a more extensive role for L. migratoria manilensis
      hunchback in anterior patterning than those described in Drosophila.

PMID- 16961592
TI  - Genomic organization, alternative splicing, and multiple regulatory regions of
      the zebrafish fgf8 gene.
AB  - Fgf8 is among the members of the fibroblast growth factor (FGF) family that play
      pivotal roles in vertebrate development. In the present study, the genomic DNA of
      the zebrafish fgf8 gene was cloned to elucidate the regulatory mechanism behind
      the temporally and spatially restricted expression of the gene in vertebrate
      embryos. Structural analysis revealed that the exon-intron organization of fgf8
      is highly conserved during vertebrate evolution, from teleosts to mammals. Close
      inspection of the genomic sequence and reverse transcription-polymerase chain
      reaction analysis revealed that zebrafish fgf8 encodes two splicing variants,
      corresponding to Fgf8a and Fgf8b, among the four to seven splicing variants known
      in mammals. Misexpression of the two variants in zebrafish embryos following mRNA
      injection showed that both variants have dorsalizing activities on zebrafish
      embryos, with Fgf8b being more potent. Reporter gene analysis of the
      transcriptional regulation of zebrafish fgf8 suggested that its complicated
      expression pattern, which is considered essential for its multiple roles in
      development, is mediated by combinations of different regulatory regions in the
      upstream and downstream regions of the gene. Furthermore, comparison of the
      genomic sequence of fgf8 among different vertebrate species suggests that this
      regulatory mechanism is conserved during vertebrate evolution.

PMID- 16961593
TI  - Hindgut specification and cell-adhesion functions of Sphox11/13b in the endoderm
      of the sea urchin embryo.
AB  - Sphox11/13b is one of the two hox genes of Strongylocentrotus purpuratus
      expressed in the embryo. Its dynamic pattern of expression begins during
      gastrulation, when the transcripts are transiently located in a ring of cells at
      the edge of the blastopore. After gastrulation, expression is restricted to the
      anus-hindgut region at the boundary between the ectoderm and the endoderm. The
      phenotype that results when translation of Sphox11/13b mRNA is knocked down by
      treatment with morpholino antisense oligonucleotides (MASO) suggests that this
      gene may be indirectly involved in cell adhesion functions as well as in the
      proper differentiation of the midgut-hindgut and midgut-foregut sphincters. The
      MASO experiments also reveal that Sphox11/13b negatively regulates several
      downstream endomesoderm genes. For some of these genes, Sphox11/13b function is
      required to restrict expression to the midgut by preventing ectopic expression in
      the hindgut. The evolutionary conservation of these functions indicates the
      general roles of posterior Hox genes in regulating cell-adhesion, as well as in
      spatial control of gene regulatory network subcircuits in the regionalizing gut.

PMID- 16961594
TI  - Treatment of coumarin-associated coagulopathy: a systematic review and proposed
      treatment algorithms.
AB  - BACKGROUND: An excessive anticoagulant effect because of coumarins is frequently
      encountered. OBJECTIVE: To review available literature on the management of
      warfarin-associated coagulopathy and to propose evidence-based treatment
      algorithms. METHODS: Data sources were Medline and Embase. Papers published
      between 1966 and December 2005 describing randomized trials or prospective cohort
      studies evaluating treatments for coumarin-associated coagulopathy were
      abstracted. RESULTS: Low dose oral vitamin K rapidly and reliably returns the
      international normalized ratio (INR) to the usual therapeutic range in non
      bleeding patients. Simple withholding of acenocumarol results in rapid correction
      of its anticoagulant effect. The impact of oral vitamin K on phenprocumon
      associated coagulopathy cannot be determined from available literature.
      Intravenous vitamin K and coagulation factors should be given to patients with
      major or life-threatening hemorrhage. The optimal dose and type of coagulation
      factor is not known. CONCLUSIONS: Vitamin K therapy is an effective treatment for
      INR prolongation in patients with coumarin-associated coagulopathy; coagulation
      factor replacement is required, in addition, in patients with major bleeding or
      with indication for immediate correction of their INR. Clinical trials powered to
      detect differences in rates of bleeding and thrombosis are now required to
      determine if vitamin K reduces the risk of bleeding without causing thrombosis in
      non-bleeding patients with prolonged INR.

PMID- 16961595
TI  - Angiogenin: a review of the pathophysiology and potential clinical applications.
AB  - Angiogenin is a member of the ribonuclease (RNase) superfamily: enzymes of innate
      substrate specificity, but divergent functional capacities. Angiogenin is a
      normal constituent of the circulation and contained in a vasculature that rarely
      undergoes proliferation, but in some physiological and pathological conditions
      its levels increase in blood, promoting neovascularization. Hence, angiogenesis
      is a common pathophysiological attribute of angiogenin. In malignant disease, the
      most studied pathological state in regard to angionenin, abnormally high levels
      are seen, which may be of prognostic significance. Angiogenin has also been
      studied in other non-malignant pathological states. The aim of this review
      article is to provide an overview of the biochemistry and physiology of
      angiogenin, specifically in relation to the human pathological states where
      angiogenin has been implicated and finally, its potential clinical applications.

PMID- 16961596
TI  - Venous thromboembolism and atherosclerosis: common denominators or different
      diseases?

PMID- 16961597
TI  - Venous thromboembolism and the risk of subsequent symptomatic atherosclerosis.
AB  - BACKGROUND: Recently, we reported an association between asymptomatic carotid
      atherosclerosis and venous thromboembolism (VTE) of unknown origin. We
      hypothesized that patients with VTE of unknown origin would be at a higher risk
      of developing symptomatic atherosclerosis than patients with VTE induced by known
      risk factors. METHODS: To examine this hypothesis, we studied 1,919 consecutive
      patients followed prospectively after their first VTE episode. The primary
      outcome was non-fatal and fatal symptomatic atherosclerotic disease in patients
      with VTE of unknown origin as compared to those with secondary VTE. An
      independent committee assessed all study outcomes, and adjusted hazard ratios
      (HR) were calculated using the Cox's proportional hazards model. RESULTS: After a
      median follow-up of 48 and 51 months, respectively, at least one symptomatic
      atherosclerotic complication was detected in 160 of the 1,063 patients (15.1%)
      with VTE of unknown origin, and in 73 of the 856 (8.5%) with secondary VTE. After
      adjusting for age and other risk factors of atherosclerosis, the HR for
      symptomatic atherosclerotic complications in patients with VTE of unknown origin
      compared to those with secondary VTE was 1.6 (95% confidence intervals; CI: 1.2
      2.0). When the analysis was restricted to patients without previous symptomatic
      atherosclerosis, the HR became 1.7 (95% CI: 1.1-2.4). CONCLUSIONS: Patients with
      VTE of unknown origin have a 60% higher risk of developing symptomatic
      atherosclerotic disease than do patients with secondary venous thrombosis.

PMID- 16961598
TI  - Subclinical atherosclerosis and the risk of future venous thrombosis in the
      Cardiovascular Health Study.
AB  - BACKGROUND: Recent reports have suggested an association of atherosclerosis with
      risk of venous thrombosis. OBJECTIVE: To confirm whether subclinical
      atherosclerosis is a risk factor for venous thrombosis (VT) among men and women
      age 65 and older. METHODS: Participants of the Cardiovascular Health Study (n =
      4,108) without baseline clinical cardiovascular disease, anticoagulant use or
      previous VT were followed for a median of 11.7 years after non-invasive
      assessment of subclinical atherosclerosis using carotid ultrasound (intima-media
      thickness and presence of plaques), ankle-brachial blood pressure index and
      electrocardiogram. Each event was classified as idiopathic or secondary. We used
      Cox proportional hazards regression to estimate the relative risk of overall and
      idiopathic VT for individuals with and without baseline subclinical
      atherosclerosis. RESULTS: There were 133 first time VT events. No subclinical
      atherosclerosis measures were associated with increased risk of overall or
      idiopathic VT. The adjusted relative risks of overall and idiopathic VT for
      presence of any type of subclinical disease were 0.60 (95% confidence interval
      0.39-0.91) and 0.32 (0.18-0.59), respectively. Most of this association was
      explained by an inverse association of high-risk carotid plaques (prevalent in
      54% of those at risk) with VT. CONCLUSION: Non-invasively measured subclinical
      atherosclerosis was not associated with increased risk of overall or idiopathic
      VT in this observational study. Carotid plaques and arterial events during follow
      up were inversely associated, a finding that requires further study.

PMID- 16961599
TI  - Why should statins prevent venous thromboembolism? A systematic literature search
      and a call for action.

PMID- 16961600
TI  - Absolute risk of venous and arterial thrombosis in HIV-infected patients and
      effects of combination antiretroviral therapy.

PMID- 16961601
TI  - Preliminary laboratory based diagnostic criteria for immune thrombocytopenic
      purpura: evaluation by multi-center prospective study.
AB  - BACKGROUND: We proposed diagnostic criteria for immune thrombocytopenic purpura
      (ITP) by modifying the existing guidelines for diagnosis of ITP and by
      incorporating laboratory tests found useful for predicting its diagnosis, for
      example erythrocyte count, leukocyte count, anti-GPIIb/IIIa antibody-producing B
      cells, platelet-associated anti-GPIIb/IIIa antibodies, percentage of reticulated
      platelets, and plasma thrombopoietin. OBJECTIVE AND METHODS: To validate our
      criteria, we conducted a multi-center prospective study involving 112 patients
      with thrombocytopenia and a morphologically normal peripheral blood film at the
      first visit. Each patient underwent a physical examination, routine laboratory
      tests, and specialized tests for the anti-GPIIb/IIIa antibody response and
      platelet turnover. RESULTS: Ninety-one patients (81%) satisfied the proposed
      criteria at first visit. Clinical diagnosis was made by skilled hematologists > 6
      months after the first visit; ITP was diagnosed in 88 patients and non-ITP
      disorders in 24. The proposed criteria had 98% sensitivity, 79% specificity, a
      95% positive predictive value, and a 90% negative predictive value. A relatively
      low specificity appears to be attributed to a few patients who had both ITP and
      aplastic anemia or myelodysplastic syndrome. CONCLUSIONS: Our preliminary
      diagnostic criteria based on ITP-associated laboratory findings were useful for
      the differential diagnosis of ITP, but additional evaluations and modifications
      will be necessary to develop criteria that can be used routinely.

PMID- 16961602
TI  - Fatal pulmonary embolism and fatal bleeding in cancer patients with venous
      thromboembolism: findings from the RIETE registry.
AB  - OBJECTIVES: To examine the clinical characteristics and outcomes of cancer
      patients with venous thromboembolism (VTE) in order to identify factors that
      place these patients at an increased risk for fatal pulmonary embolism (PE) or
      fatal bleeding. PATIENTS AND METHODS: Registro Informatizado de la Enfermedad
      Trombo Embolica (RIETE) is a prospective registry of consecutive patients with
      symptomatic, objectively confirmed, acute VTE. RESULTS: Up to January 2006, a
      total of 14 391 patients with symptomatic acute VTE were enrolled in RIETE, of
      whom 2945 (20%) had cancer. During the 3-month follow-up period the frequency of
      fatal PE in cancer patients was 2.6%, and that of fatal bleeding 1.0%. These
      frequencies were significantly higher than in VTE patients without cancer (1.4%
      and 0.3%, respectively). In patients with cancer, abnormal renal function,
      metastatic disease, recent major bleeding and recent immobility for >or= 4 days
      (42% of the 108 patients who died from PE or bleeding had recent immobility) were
      factors independently associated with an increased risk for both fatal PE and
      fatal bleeding. In addition, PE diagnosis on admission was an independent risk
      factor for fatal PE, while body weight < 60 kg was an independent risk factor for
      fatal bleeding. CONCLUSIONS: Both fatal PE and fatal bleeding are more common in
      cancer patients with VTE than in those patients without cancer. In cancer
      patients, abnormal renal function, metastatic disease, recent major bleeding and
      recent immobility for >or= 4 days are associated with an increased risk for both
      fatal PE and fatal bleeding.

PMID- 16961603
TI  - Prior use of antithrombotic agents and neurological functional outcome at
      discharge in patients with ischemic stroke.
AB  - BACKGROUND: Studies in experimental animals have suggested that antithrombotic
      agents may have a neuroprotective effect after an ischemic injury. The aim of
      this study was to analyze the effect of prior use of antithrombotic agents
      (antiplatelets or anticoagulants) on neurological functional outcome in patients
      with acute ischemic stroke. SUBJECTS AND METHODS: Consecutive patients included
      in the Perugia Stroke Registry were considered for this analysis. Neurological
      functional outcome was evaluated at discharge using the modified Rankin Scale
      (mRS >or= 3 disabling stroke). RESULTS: Of the 1921 patients included in the
      analysis (mean age 76.3 +/- 12.5 years; 53% males), 662 (34.5%) were on
      antithrombotic treatment (581 antiplatelets, 71 anticoagulants and 10
      antiplatelets associated with anticoagulants). One hundred and twenty-two
      patients (6.4%) died in hospital; at discharge 712 patients (37.1%) were disabled
      and 1,087 patients (56.6%) were non-disabled. Fifty-four (44.3%) of the deceased
      patients and 270 (37.9%) of disabled patients were on antithrombotic treatment,
      while 338 (31.1%) non-disabled patients were taking antithrombotic agents. From
      multivariate analysis, age and stroke severity were associated with an adverse
      outcome. Male gender, dyslipidemia, stroke due to small vessel disease and no
      history of previous stroke were associated with an improved outcome, while no
      correlation was found between prior use of antithrombotic agents and outcome
      (mortality odds ratio; OR = 1.32, 95% confidence interval; CI 0.85-2.04; P =
      0.20, mortality or disability OR = 0.95, 95% CI 0.72-1.25; P = 0.80). CONCLUSION:
      Prior use of antithrombotic agents does not improve the functional outcome in
      patients with acute ischemic stroke.

PMID- 16961604
TI  - Molecular weight fibrinogen variants determine angiogenesis rate in a fibrin
      matrix in vitro and in vivo.
AB  - BACKGROUND: During wound repair, fibrin acts both as a barrier to prevent blood
      loss and as a temporary matrix for the invasion and ingrowth of endothelial and
      tissue cells. A well-controlled angiogenesis process in the fibrinous exudate
      matrix is crucial for optimal wound healing. The composition and structure of the
      fibrin matrix are important determinants of the invasion of endothelial cells and
      capillary-tube formation into the matrix. OBJECTIVE: Fibrinogen circulates in a
      high and low molecular weight form (HMW and LMW, respectively) and the purpose of
      this study was to investigate how fibrin matrices from these naturally occurring
      fibrinogen variants influence angiogenesis. Angiogenesis was studied using an in
      vitro model in which human microvascular endothelial cells (hMVEC) were cultured
      on three-dimensional fibrin matrices from different fibrinogen forms, and using
      two in vivo mouse models. RESULTS: The in vitro angiogenesis in an HMW-fibrin
      matrix shows increased cell and tubular structure ingrowth compared with
      unfractionated fibrin matrix (median increase 58%, range 46-234%). The ingrowth
      of tubular structures in an LMW-fibrin matrices is decreased when compared with
      unfractionated fibrin (median decrease 70%, range 67-100%). Similar results were
      observed for in vivo angiogenesis. CONCLUSIONS: The naturally occurring
      fibrinogen variants HMW- and LMW-fibrin modulate the angiogenic capacity of
      endothelial cells in fibrin matrices. The different effects of the molecular
      weight fibrinogen variants provide further insight in the matrix characteristics
      in angiogenesis and could possibly be applied in the context of tissue
      engineering and wound healing.

PMID- 16961605
TI  - Effects of factor XI deficiency on ferric chloride-induced vena cava thrombosis
      in mice.
AB  - BACKGROUND: Increased plasma levels of coagulation factor (F) XI are a risk
      factor for venous thrombosis. OBJECTIVE: To further explore the relationship
      between FXI and venous thrombosis, we evaluated FXI-deficient and wild-type mice
      in a ferric chloride (FeCl(3))-induced vena cava thrombosis model. METHODS AND
      RESULTS: Thrombosis was induced by 3-min topical application of filter papers
      containing increasing concentrations of FeCl(3) and the thrombus was measured at
      30 min. In contrast to wild-type mice, FXI-deficient mice failed to form a
      thrombus with 5% FeCl(3,) and were partially protected against 7.5% and 10%
      FeCl(3,) respectively. The protective effect was substantially stronger than a
      high dose of heparin (1,000 units kg(-1), i.v.), clopidogrel (30 mg kg(-1), p.o.)
      or argatroban (30 mg kg(-1), i.p.). These antithrombotic agents resulted in off
      scale bleeding in a tail bleeding time assay, whereas the bleeding time of FXI
      deficient mice was unchanged compared to wild-type mice. In addition to its known
      effect on the coagulation cascade, enhanced clot lysis was demonstrated in FXI
      deficient mouse and human plasma compared to those supplemented with FXIa.
      CONCLUSION: Given the strong antithrombotic efficacy (possibly contributed by
      strong anticoagulant activity associated with increased fibrinolytic activity)
      and mild bleeding diathesis associated with FXI deficiency, therapeutic
      inhibition of FXI may be a reasonable therapeutic strategy to treat or prevent
      venous thrombosis.

PMID- 16961606
TI  - A comparison of the beta-D-xyloside, odiparcil, to warfarin in a rat model of
      venous thrombosis.
AB  - BACKGROUND: A significant need exists for new chronic oral anticoagulation
      therapies to replace warfarin. Previous studies have shown that beta-D-xylosides,
      which prime glycosaminoglycan (GAG) synthesis, have antithrombin and
      antithrombotic activity. In the following report, a new orally active beta-D
      xyloside (odiparcil) has been characterized in a rat model of venous thrombosis
      and its efficacy and bleeding liability compared to warfarin. Additionally,
      studies were conducted to investigate odiparcil's ex vivo antithrombin and
      antiplatelet activity, and also to explore the potential utility of protamine
      sulfate as a neutralizing agent. METHODS AND RESULTS: In vivo thrombosis studies
      were conducted in a rat inferior vena cava model, and bleeding studies in a rat
      tail transection model. Following oral dosing, warfarin and odiparcil produced
      dose-related suppression of thrombus formation. A therapeutically relevant dose
      of warfarin in this model (international normalized ratio; INR 3.0) achieved
      approximately 65% inhibition of thrombus formation. Warfarin caused dose-related
      significant increases in bleeding indices. Odiparcil antithrombotic activity was
      limited by its mechanism to a maximum suppression of thrombus formation of 65
      70%, and did not prolong bleeding indices. Additionally, odiparcil-induced
      heparin cofactor II (HCII)-dependent antithrombin activity was shown to be a
      function of dermatan sulfate-like GAG production. Other than thrombin-related
      effects, no odiparcil effects on platelet function were observed. In antidote
      studies, it was demonstrated that odiparcil-induced antithrombotic activity could
      be partially neutralized by protamine sulfate. CONCLUSIONS: These experiments
      suggest that an antithrombotic approach based upon xyloside induction of
      circulating GAGs may have the potential to approximate the efficacy of warfarin
      and yet with a reduced risk to hemostasis.

PMID- 16961607
TI  - In vitro characterization of missense mutations associated with quantitative
      protein S deficiency.
AB  - OBJECTIVE: To elucidate the molecular consequences of hereditary protein S (PS)
      deficiency, we investigated the in vitro synthesis of the PS missense mutants in
      COS-1 cells and their activated protein C (APC) cofactor activities. PATIENTS:
      Four patients with quantitative PS deficiency suffering from venous thrombosis
      were examined. RESULTS: We identified three distinct novel missense mutations,
      R275C, P375Q and D455Y, and two previously reported missense mutations, C80Y and
      R314H. The P375Q and D455Y mutations were found in one patient and observed to be
      in linkage on the same allele. The R314H mutant showed the lowest level of
      expression (32.7%), and the C80Y, P375Q + D455Y, and R275C mutants exhibited a
      moderate impairment of expression, that is, 43.8%, 49.5%, and 72.3% of the wild
      type, respectively. Furthermore, pulse-chase experiments demonstrated that all
      mutants showed impaired secretion and longer half-lives in the cells than the
      wild type PS. In the APC cofactor assays, the C80Y mutant showed no cofactor
      activity, and the R275C mutant showed reduced activity, 62.3% of the wild type
      PS, whereas the R314H and P375Q + D455Y mutants exhibited normal cofactor
      activity. CONCLUSION: These data indicate that the C80Y and R275C mutations
      affect the secretion and function of the PS molecule, and that the R314H and
      P375Q + D455Y mutations are responsible for only secretion defects, causing the
      phenotype of quantitative PS deficiency observed in the patients.

PMID- 16961608
TI  - Plasma protein S activity correlates with protein S genotype but is not sensitive
      to identify K196E mutant carriers.
AB  - BACKGROUND: Protein S (PS) is an anticoagulant protein that functions as a
      cofactor for activated protein C (APC), and congenital PS deficiency is a well
      known risk factor for the development of deep vein thrombosis (DVT). Recently, we
      and others identified the K196E missense mutation in the second epidermal growth
      factor-like domain of PS as a genetic risk factor for DVT in the Japanese
      population. The incidence of this mutation is high in the Japanese population.
      OBJECTIVES: In the present study, we investigated the relationship between plasma
      PS activity and the presence of the K196E mutation. PATIENTS AND METHODS: We
      measured PS activity as a cofactor activity for APC in 1,862 Japanese individuals
      and determined the PS K196E genotype in this population. RESULTS: Individuals
      heterozygous for the mutant E-allele had lower plasma PS activity than wildtype
      subjects (mean +/- SD, 71.9 +/- 17.6%, n = 34 vs. 87.9 +/- 19.8%, n = 1,828, P <
      0.0001). However, the PS activity of several heterozygous individuals (n = 8) was
      greater than the population average. In contrast, multiple wildtype subjects (n =
      26) had PS activity less than 2 SD below the population mean, indicating that
      other genetic or environmental factors affect PS activity. CONCLUSIONS: Plasma PS
      activity itself is not suitable for identifying PS 196E carriers and other
      methods are required for carrier detection.

PMID- 16961609
TI  - Distinct antithrombotic consequences of platelet glycoprotein Ibalpha and VI
      deficiency in a mouse model of arterial thrombosis.
AB  - BACKGROUND: Collagen and von Willebrand factor (VWF) are considered essential to
      initiate platelet deposition at sites of vascular injury, but their respective
      roles remain to be elucidated. METHODS: We used a model of carotid artery
      thrombosis induced by a ferric chloride injury to compare the time to first
      occlusion and occlusion rate at 25 min postinjury in mice lacking the collagen
      receptor, glycoprotein (GP) VI, or the ligand-binding domain of the VWF receptor,
      GP Ibalpha. RESULTS: In normal mice used as controls (n = 12), a complete
      obstruction of blood flow developed within 8.05 +/- 0.47 min (mean +/- SEM), and
      the occlusion rate was 100%. The results were variable in 26 GP VI(-/-) mice. The
      artery never occluded in eight mice, but the time to first occlusion in the
      remaining 18 (8.36 +/- 0.27 min) was not different from normal (P = 0.556).
      Nonetheless, the occlusion rate was 42%, because in seven mice the occluded
      artery reopened and stayed patent at 25 min. In contrast, the artery never
      occluded in 12 mice lacking GP Ibalpha. In ex vivo perfusion experiments, GP VI(
      /-) platelets failed to form thrombi onto collagen type I fibrils, but formed
      thrombi of normal size when exposed to endothelial or fibroblast extracellular
      matrix. CONCLUSIONS: Absence of GP Ibalpha function has a more profound
      antithrombotic effect in vivo than absence of the GP VI-dependent pathway of
      collagen-induced adhesion/activation. Components of the extracellular matrix may
      elicit a thrombogenic response in the absence of GP VI but not GP Ibalpha.

PMID- 16961610
TI  - Recombinant factor VIIa reverses the inhibitory effect of aspirin or aspirin plus
      clopidogrel on in vitro thrombin generation.
AB  - BACKGROUND: Antiplatelet drugs constitute the therapy of choice for acute
      coronary syndromes, but bleeding can be a side-effect requiring treatment.
      Restoration of normal platelet activity is also mandatory before urgent surgery.
      This study investigated: (a) whether a regimen of aspirin or clopidogrel plus
      aspirin significantly inhibited platelet thrombin generation (TG); and (b) the
      reversal of this inhibition by recombinant activated factor VII (rFVIIa). METHODS
      AND RESULTS: TG was evaluated by the lag time, time to peak, peak of TG, and area
      under the curve after 35 min of assay (AUC(0 --> 35 min)). These measures were
      examined by the calibrated automated thrombography method in 22 healthy
      volunteers, 22 volunteers after a 100 mg day(-1) aspirin intake (200 mg first
      day) for 5-7 days, and 22 healthy volunteers after aspirin 100 mg day(-1) (200 mg
      first day) plus clopidogrel 75 mg day(-1) (300 mg first day) for 4-7 days. The TG
      parameters were measured under basal conditions and after platelet stimulation by
      sodium arachidonate (AA), adenosine 5'-diphosphate (ADP), collagen and rFVIIa in
      normal non-aspirinated as well as in vivo aspirinated platelet-rich plasma (PRP)
      or aspirin plus clopidogrel PRP. Lag time was shorter (P < 0.05), and peak of TG
      and AUC(0 --> 35 min) were significantly greater (P < 0.01 for both), in PRP
      activated with ADP, collagen, AA or FVIIa than in non-activated PRP from normal
      subjects. Both non-activated PRP and activated PRP prepared from platelets
      obtained from volunteers after aspirin intake showed significant prolongation of
      the time parameters but there was less effect on peak of TG and AUC(0 --> 35
      min). For most parameters, aspirin plus clopidogrel administration showed to be
      more effective compared with the effect obtained by aspirin alone. When rFVIIa
      was added to ASA-PRP or ASA + Clop PRP, lag time (P < 0.001 for all) and time to
      peak (P < 0.001-0.017) were significantly shortened, indicating that rFVIIa
      reverses the inhibitory effect of these anti-aggregating agents. CONCLUSION:
      Platelets activated by AA, ADP, collagen or FVIIa triggered TG. This effect was
      inhibited by aspirin plus clopidogrel, suggesting an additional benefit of this
      drug combination for preventing thrombosis. rFVIIa reverses the inhibitory effect
      of aspirin or aspirin plus clopidogrel, and could be useful for bleeding
      complications or when acute surgery is needed during treatment with these
      antiplatelet drugs.

PMID- 16961611
TI  - Blood platelets activate the classical pathway of human complement.
AB  - OBJECTIVE: Activation of the complement system plays a key role in inflammation
      associated with vascular injury. Recently, platelet P-selectin was shown to
      activate C3 via the alternative pathway of human complement. As platelets also
      posses binding sites for C1q, the recognition unit of the classical complement
      pathway, the present study examined classical pathway activation on platelets.
      METHODS: Complement activation was assessed by either a solid phase enzyme-linked
      immunosorbent assay (ELISA) or flow cytometry. RESULTS: Using the ELISA approach,
      2- to 10-fold increases (P < 0.001) in C1q and C4d deposition were demonstrated
      on adherent platelets following exposure (60 min 37 degrees C) to diluted (1/10)
      human plasma or serum. Similar results were obtained by flow cytometry using
      activated platelets in suspension. C1q and C4d deposition on platelets was
      accompanied by an approximately 4-fold increase in fluid phase C4d and C3a
      generation. Consistent with activation of the classical complement pathway, C4
      cleavage failed to occur in serum depleted of C1q but was unchanged in factor B
      deficient serum. C4 activation was enhanced by platelet stimulation using
      chemical (SFLLRN peptide) or mechanical (shear) means, and decreased following
      platelet exposure to plasmin. These treatments were accompanied by changes in
      platelet surface gC1qR/p33 expression, a cellular C1q binding protein. In
      purified systems, recombinant gC1qR/p33 supported C4 activation, in a C1q
      dependent manner. CONCLUSION: These data provide the first evidence for C1q
      dependent classical complement pathway activation on platelets, and support a
      role for gC1qR/p33 in this process. However, monoclonal antibodies (mAb) to
      gC1qR/p33 produced only modest (20% +/- 8%, mean +/- SD, n = 5) reductions in C4
      activation on platelets. Thus, further studies are required to investigate the
      involvement of additional platelet membrane constituents in classical complement
      pathway activation.

PMID- 16961612
TI  - Platelet hyperreactivity generalizes to multiple forms of stimulation.
AB  - BACKGROUND: Although platelet hyperreactivity constitutes an important
      cardiovascular risk factor, standardized methods for its measurement are lacking.
      We recently reported that aggregometry using a submaximal concentration of
      epinephrine identifies individuals with in vitro platelet hyperreactivity; this
      hyperreactivity was reproducible on multiple occasions over long periods of time.
      OBJECTIVE AND METHODS: To better understand this aberrant reactivity, we studied
      in a large group of subjects (n = 386) the relationship between healthy
      individuals' platelet reactivity to epinephrine and their platelet phenotype as
      measured by other functional assays. RESULTS: Subjects with hyperreactivity to
      epinephrine were more likely to exhibit hyperfunction in each major aspect of
      platelet activity, including adhesion (response to low-dose ristocetin; P <
      0.001), activation (surface P-selectin expression and PAC-1 binding after
      stimulation; P <or= 0.003) and aggregation to other agonists [no agonist,
      adenosine diphosphate (ADP), arachidonic acid, collagen, collagen-related peptide
      and ristocetin; P <or= 0.025] and to applied shear stress (PFA-100 and cone-and
      plate viscometer; P < 0.05). These differences persisted after adjusting for
      demographic and hematologic differences between groups. We studied candidate
      genes relevant to epinephrine-mediated platelet activation and found that
      hyperreactivity to epinephrine was associated with a polymorphism on the gene
      (GNB3) encoding the beta-3 subunit of G proteins (P = 0.03). CONCLUSIONS: Robust
      aggregation to a submaximal concentration of epinephrine establishes a true
      hyperreactive platelet phenotype that is 'global' as opposed to agonist specific;
      detection of this phenotype could be useful for studying patients at risk for
      arterial thrombosis. The mechanisms underlying hyperreactivity to different types
      of platelet stimulation may share common signaling pathways, some of which may
      involve specific G protein subunits.

PMID- 16961613
TI  - Is chronic liver disease associated with a bleeding diathesis?

PMID- 16961614
TI  - Methodological issues with coagulation testing in patients with liver disease.

PMID- 16961615
TI  - Consequences of abnormal hemostasis tests for clinical practice.

PMID- 16961616
TI  - Hemostasis in chronic liver disease.

PMID- 16961617
TI  - How to concile bleeding and thrombotic tendency in liver cirrhosis?

PMID- 16961618
TI  - Successful outcome of using recombinant activated factor VII (rFVIIa) in liver
      biopsy in a patient with liver failure.

PMID- 16961619
TI  - Duration of symptoms and D-dimer testing in the ruling-out of venous
      thromboembolism.

PMID- 16961620
TI  - Cholesteryl ester transfer protein genotypes associated with venous thrombosis
      and dyslipoproteinemia in males.

PMID- 16961621
TI  - Phase 2, randomized, double-blind, placebo-controlled, multicenter clinical
      evaluation of recombinant human thrombin in multiple surgical indications.

PMID- 16961622
TI  - Acquired von Willebrand disease: potential contribution of the VWF:CB to the
      identification of functionally inhibiting auto-antibodies to von Willebrand
      factor.

PMID- 16961623
TI  - von Willebrand factor collagen binding assay in von Willebrand disease type 2A,
      2B, and 2M.

PMID- 16961624
TI  - Barriers to the long-term use of low-molecular weight heparins for treatment of
      cancer-associated thrombosis.

PMID- 16961625
TI  - Circulating tissue factor accumulates in thrombi, but not in hemostatic plugs.

PMID- 16961626
TI  - A prospective replication study of five gene variants previously associated with
      risk of myocardial infarction.

PMID- 16961627
TI  - Role of the P2Y12 gene polymorphism in platelet responsiveness to clopidogrel in
      healthy subjects.

PMID- 16961628
TI  - More on: platelet function analyser (PFA)-100 closure time in the evaluation of
      platelet disorders and platelet function.

PMID- 16961629
TI  - Severe strongyloidiasis in corticosteroid-treated patients.
AB  - Severe strongyloidiasis, caused by Strongyloides stercoralis, is a preventable
      life-threatening disease that can occur in any corticosteroid-treated patient who
      has travelled to a country with infested soil, even if the contact occurred up to
      30 years previously. This diagnosis should be considered in corticosteroid
      treated patients who experience either unusual gastrointestinal or pulmonary
      symptoms, or who suffer from unexplained sepsis caused by Gram-negative bacilli.
      Peripheral eosinophilia is not observed systematically and, even if present, is
      moderate in most cases. Ivermectine is the best prophylactic and therapeutic
      option, and thiabendazole should no longer be used. However, guidelines for the
      prevention and management of S. stercoralis infection in such patients have not
      yet been established.

PMID- 16961630
TI  - Clinical manifestations, treatment and outcome of Paecilomyces lilacinus
      infections.
AB  - The fungus Paecilomyces lilacinus is an emerging pathogen that causes severe
      human infections, including devastating oculomycosis. Usually, it shows low
      susceptibility to conventional antifungal drugs in vitro, and variable
      susceptibility to novel triazoles. A review of the published literature
      identified 119 reported cases of human infection by P. lilacinus between 1964 and
      2004. Most were cases of oculomycosis (51.3%), followed by cutaneous and sub
      cutaneous infections (35.3%), and a smaller group of miscellaneous infections
      (13.4%). Lens implantation is the most frequent predisposing factor for
      oculomycosis. Cutaneous and sub-cutaneous infections occur mainly in solid organ
      and bone marrow transplant recipients, although surgery and primary or acquired
      immunodeficiency are also relevant predisposing factors. Infections in apparently
      immunocompetent patients have also been reported. Surgical debridement combined
      with antifungal drug therapy, or the correction of predisposing factors, such as
      neutropenia, are usually required to obtain improvement. Treatment with
      traditional antifungal drugs often fails. Voriconazole has demonstrated good
      activity in both cutaneous and ocular infections in the few cases in which this
      drug has been used. The new triazoles ravuconazole and posaconazole show good in
      vitro activity against P. lilacinus and could be promising therapeutic
      alternatives.

PMID- 16961631
TI  - Susceptibility to diphtheria in adults: prevalence and relationship to gender and
      social variables.
AB  - Recent outbreaks of diphtheria have drawn attention to the re-emergence of this
      disease. This study investigated susceptibility to diphtheria in north-east
      Germany and its relationship to gender and social factors. A study population of
      4275 individuals recruited for the population-based Study of Health in Pomerania
      (SHIP) was available for analysis. IgG antibodies against diphtheria toxin were
      determined by ELISA and were used to define susceptibility to diphtheria (i.e.,
      IgG titres < 0.1 IU/mL). The prevalence of susceptibility to diphtheria was
      32.4%. Multivariate analysis revealed 45% increased odds of women being
      susceptible to diphtheria. Women who had not received diphtheria toxoid
      vaccination during the previous 10 years had four-fold increased odds of being
      susceptible to diphtheria toxin compared with unvaccinated men. None of the
      social factors investigated was associated with susceptibility status. It was
      concluded that a high proportion of middle-aged adults was susceptible to
      diphtheria. Women lacked seroprotection more often than men, which might be
      explained, in part, by gender-specific immune responses following vaccination.
      There is a need for information campaigns to improve public awareness of these
      problems.

PMID- 16961632
TI  - Prevalence and correlates of diphtheria toxoid antibodies in children and adults
      in Israel.
AB  - A seroepidemiological study was performed to evaluate immunity to diphtheria and
      to determine the correlates of diphtheria toxoid antibody levels among children
      and adults in Israel. In total, 3,185 sera from an age-stratified sample of
      children and adults, obtained in 2000-2001, were tested for diphtheria toxoid
      antibodies by an in-house double-antigen ELISA. A level of <or=0.01 IU/mL (no
      immune protection or seronegativity) was found in 168 (5.3%) of the 3,185
      subjects, 639 (20.1%) had antibody levels of 0.011-0.099 IU/mL (basic immunity or
      low seropositivity), and 2,378 (74.7%) had antibody levels >or=0.1 IU/mL (full
      protection or seropositivity). Seronegativity increased significantly in subjects
      aged >50 years, reaching levels of 9.7%, 12.6% and 18.9% in the groups aged 50
      54, 55-59 and >60 years, respectively (p 0.001), with rates of basic immunity
      following a similar pattern. Subjects born abroad had higher seronegativity rates
      than those born in Israel (7.7% vs. 4.9%; p 0.019). No difference in diphtheria
      toxoid antibody levels was found according to other demographical variables, such
      as gender, Jewish or Arab ethnicity, urban or rural settlements, and the
      subjects' place of residence. The level of immunity to diphtheria among children
      and adults in Israel was satisfactory, with the exception of individuals aged >50
      years. The risk of diphtheria outbreaks is low, but sporadic cases may occur
      among individuals lacking basic immunity against the disease.

PMID- 16961633
TI  - Risk-factors for gastrointestinal colonisation with resistant Enterobacteriaceae
      among hospitalised patients: a prospective study.
AB  - This study assessed the incidence of gastrointestinal colonisation by resistant
      Enterobacteriaceae among hospitalised patients, and identified risk-factors for
      ceftazidime and ofloxacin resistance. A prospective cohort study was performed in
      five wards in a French teaching hospital during a 2-year period. Patients
      hospitalised for > 48 h were enrolled between 17 April 2000 and 30 April 2002. A
      rectal swab was taken at admission, then once-weekly and/or on the day of
      discharge. In total, 933 patients were investigated and 585 amoxycillin-resistant
      isolates were obtained. Resistance rates for ceftazidime and ofloxacin were 9.4%
      and 4.8%, respectively. Multivariate analysis indicated that previous
      hospitalisation (p < 0.004) and exposure to amoxycillin-clavulanate (p < 0.003)
      and ceftriaxone (p < 0.002) were associated significantly with ceftazidime
      resistance. Hospitalisation in the urology ward (p < 0.02) and previous exposure
      to fluoroquinolones (p < 0.01) were the two independent risk-factors associated
      with ofloxacin resistance. The results of the study confirmed that antibiotic use
      selected resistant Enterobacteriaceae from the gut flora. Resistance was observed
      mostly in patients with previous antibiotic exposure and previous hospitalisation
      in wards with a high antibiotic selection pressure.

PMID- 16961634
TI  - Factors associated with multidrug-resistant bacteria in secondary peritonitis:
      impact on antibiotic therapy.
AB  - Secondary peritonitis includes community-acquired and nosocomial peritonitis.
      These intra-abdominal infections have a common pathogenesis but some
      microbiological differences, particularly with respect to the type of bacteria
      recovered and the level of antimicrobial susceptibility. This report describes a
      prospective observational study of 93 consecutive patients with secondary
      peritonitis during an 11-month period. Community-acquired peritonitis accounted
      for 44 cases and nosocomial peritonitis for 49 cases (post-operative in 35
      cases). Fifteen multidrug-resistant (MDR) bacteria were recovered from 14
      patients. In univariate analysis, the presence of MDR bacteria was associated
      significantly with pre-operative and total hospital lengths of stay, previous use
      of antimicrobial therapy, and post-operative antimicrobial therapy duration and
      modifications. A 5-day cut-off in length of hospital stay had the best
      specificity (58%) and sensitivity (93%) for predicting whether MDR bacteria were
      present. In multivariate analysis, only a composite variable associating pre
      operative hospital length of stay and previous use of antimicrobial therapy was a
      significant independent risk-factor for infection with MDR bacteria. In
      conclusion, knowledge of these two factors may provide a more rational basis for
      selecting initial antimicrobial therapy for patients with secondary peritonitis.

PMID- 16961635
TI  - Central venous catheter-related Stenotrophomonas maltophilia bacteraemia and
      associated relapsing bacteraemia in haematology and oncology patients.
AB  - This retrospective study investigated the clinical significance and impact of
      Stenotrophomonas maltophilia bacteraemia in 49 haematology and oncology patients
      at a tertiary referral medical centre in Taipei between July 1999 and December
      2003. Sixteen patients had 24 episodes of central venous catheter (CVC)-related
      bacteraemia, with the main clinical characteristics being a nosocomial
      bacteraemia (100%), preceding antibiotic therapy (94%), bacteraemia developed in
      a general ward (87%), immunosuppressive therapy (75%), in-situ CVC-related
      bacteraemia (75%), and neutropenia (63%). Only four (25%) patients had
      inflammatory signs at the CVC site following diagnosis of bacteraemia. Five
      patients had recurrent bacteraemia, with risk-factors being long-lasting (>10
      days) neutropenia (p 0.036) and an initial failure to remove the CVC (p 0.001).
      These cases did not involve re-infection, as the same S. maltophilia strain was
      identified following random amplified polymorphic DNA (RAPD) analysis of the
      initial and subsequent isolates. However, relapses could occur after long latency
      periods (maximum, 200 days). Most patients were cured after removal of the CVC,
      even without appropriate antibiotic treatment. Physicians should have a high
      index of suspicion for CVC-related bacteraemia with haematology and oncology
      patients with CVCs and S. maltophilia bacteraemia. In addition to appropriate
      antibiotic therapy, removal of the CVC is crucial for successful treatment of CVC
      related S. maltophilia bacteraemia and prevention of relapses.

PMID- 16961636
TI  - O148 Shiga toxin-producing Escherichia coli outbreak: microbiological
      investigation as a useful complement to epidemiological investigation.
AB  - An outbreak of Shiga toxin-producing Escherichia coli (STEC) O148 infection
      occurred among wedding attendees in France in June 2002. A retrospective cohort
      study was performed and ten cases were identified, including two adults with
      haemolytic uraemic syndrome (HUS). The analytical study revealed that > 80% of
      affected individuals had eaten lightly roasted mutton and poultry pate, but only
      the consumption of pate tended to be associated with illness (relative risk 3.4;
      95% CI 0.8-14.4). Left-overs (cooked mutton and raw offal) and processed foods
      (pate) from the same batches as served at the party were sampled. Human, food and
      environmental samples were examined for the Shiga toxin (stx) gene and virulence
      traits by PCR. Stx-positive samples were cultured for STEC. HUS cases were tested
      for serum antibodies against 26 major STEC serogroups. An STEC O26 strain (stx1,
      eae, ehxA) was isolated from one case with diarrhoea, and an STEC O148 strain
      (stx2c) from one case of HUS. Serum antibodies against O26 were not detected in
      either of these patients; antibodies against O148 were not tested. Three STEC
      strains were isolated from the mutton and the offal (stx2c, O148), and two from
      the pate (stx2c, O-X and O-Y). The isolates from the mutton were
      indistinguishable from the human stx2c isolate, whereas the pate isolates
      differed. Although four different STEC strains were identified in patients and
      foods, the results of molecular subtyping, in conjunction with analysis of food
      consumption patterns, strongly suggested that this outbreak was caused by mutton
      contaminated with STEC O148.

PMID- 16961637
TI  - Salmonella enterica serotype Virchow: epidemiology, resistance patterns and
      molecular characterisation of an invasive Salmonella serotype in Israel.
AB  - This study outlines the unique epidemiology of Salmonella enterica serotype
      Virchow in Israel. Between 1997 and 2002, the overall incidence of non-typhoid
      Salmonella enterica (NTS) decreased from 69.3 to 53.3 infections/100,000
      population, but the incidence of S. Virchow increased (from 7.2 to 9.1
      infections/100,000). Since 2000, S. Virchow has become the second-ranking NTS
      isolate, accounting for 17% and 27% of all stool and blood NTS isolates,
      respectively. Infants aged < 1 year had the highest incidence of isolation from
      stools (92.8/100,000). The incidence of isolation from blood was highest for
      infants aged <1 year (4.4/100,000). Only 6% of isolates were susceptible to all
      ten antibiotic agents tested; 34% were resistant to one agent, 54% to one to
      three agents, and 40% to four to six agents. A high proportion of the tested
      isolates were resistant to nalidixic acid (89%), streptomycin (56%), tetracycline
      (43%), trimethoprim-sulphamethoxazole (38%) and chloramphenicol (28%), but none
      to ciprofloxacin or ceftriaxone. Pulsed-field gel electrophoresis revealed two
      closely related clusters, each containing a predominant pulsotype. Coupled with
      its invasive propensity, the increasing incidence of highly resistant S. Virchow
      in Israel is of real concern. Future research should focus on the sources of S.
      Virchow in the food chain in order to institute effective control measures.

PMID- 16961638
TI  - The possible significance of Clostridium spp. in blood cultures.
AB  - The significance of Clostridium spp. in blood cultures was evaluated by two
      methods. In the first part of the study, a group of 80 patients with Clostridium
      spp. bacteraemia was compared with a group of 100 patients with Bacillus spp. in
      blood cultures, making the assumption that Bacillus almost invariably represents
      contamination (pseudobacteraemia). Significant differences were found between the
      two groups, suggesting that growth of Clostridium did not represent
      pseudobacteraemia. Patients with Clostridium bacteraemia were older, had a higher
      frequency of gastrointestinal disease (especially colorectal tumours), were
      associated more frequently with polymicrobial bacteraemia, and had a higher
      mortality rate. In the second part of the study, each of the 80 cases of
      Clostridium bacteraemia was evaluated individually for clinical relevance by an
      infectious diseases expert. In two-thirds of the cases, isolates of Clostridium
      from blood were considered to be of clinical relevance, whereas in one-third of
      cases, the clinical significance of this finding was doubtful. It was concluded
      that growth of Clostridium spp. in blood cultures, even in the absence of one of
      the histotoxic syndromes, is often of clinical significance, and that such
      findings should be properly evaluated and not ignored.

PMID- 16961639
TI  - Occurrence of qnrA-positive clinical isolates in French teaching hospitals during
      2002-2005.
AB  - Bacteria harbouring the novel qnrA plasmid-mediated mechanism of quinolone
      resistance have been described in different countries, but the frequency of their
      occurrence has not been investigated. In total, 1,468 clinical isolates of
      Enterobacteriaceae with quinolone resistance or extended-spectrum beta-lactamase
      (ESBL) phenotypes were collected from eight teaching hospitals in France during
      2002-2005 and screened for qnrA. Overall, 28 isolates (22 Enterobacter cloacae,
      three Klebsiella pneumoniae, one Citrobacter freundii, one Klebsiella oxytoca and
      one Proteus mirabilis) were positive for qnrA, representing 1.9% of all isolates,
      3.3% of ESBL-producing isolates (22% of the E. cloacae isolates) and 0% of non
      ESBL-producing isolates. The prevalence of qnrA among consecutive ESBL-producing
      isolates in 2004 from the eight hospitals was 2.8% (18/639). Of the qnrA-positive
      isolates, 100% were intermediately-resistant or resistant to nalidixic acid, and
      75% to ciprofloxacin. Twenty-one of the 22 qnrA-positive E. cloacae isolates were
      obtained from two hospitals in the Paris area, and molecular typing and plasmid
      content analysis showed clonal relationships for five, three and two isolates,
      respectively. The qnrA genetic environment was similar to that of the In36
      integron. The remaining two isolates had qnrA variants (30 and 29 nucleotide
      differences, respectively, compared with the original sequence) and an unknown
      genetic environment. The ESBL gene associated with qnrA was bla(SHV-12) in most
      of the isolates, but bla(PER-1) and bla(SHV-2a) were found in two isolates. In
      France, it appears that qnrA-positive isolates are predominantly E. cloacae
      isolates producing SHV-12, and may be associated with the dissemination of an
      In36-like integron.

PMID- 16961640
TI  - Plasmid-mediated quinolone resistance determinant qnrS in Enterobacter cloacae.
AB  - PCR was used to investigate the occurrence of the plasmid-encoded quinolone
      resistance determinants qnrA and qnrS among diarrhoeagenic enterobacterial
      isolates recovered from Hanoi, Vietnam, during the period March 2001 to April
      2002. In total, 162 Escherichia coli isolates, 28 Shigella isolates and three
      Enterobacter cloacae isolates were negative for qnrA, while a single Ent. cloacae
      isolate harboured a 50-kb qnrS-positive conjugative plasmid. Cloning and
      sequencing identified a qnrS gene bracketed by open reading frames identical to
      those surrounding the qnrS gene of a Shigella flexneri isolate from Japan,
      thereby suggesting a common mechanism of acquisition.

PMID- 16961641
TI  - Conventional and molecular investigation of meningococcal isolates in relation to
      two outbreaks in the area of Athens, Greece.
AB  - Two local outbreaks caused by serogroup B Neisseria meningitidis occurred in the
      Athens area of Greece during 2003. In total, 30 N. meningitidis isolates from
      patients and carriers, as well as sporadic cases, were investigated by
      conventional techniques (serogroup, serotype and serosubtype), multilocus
      sequence typing (MLST), analysis of variable number tandem repeats (VNTR) and
      random amplified polymorphic DNA (RAPD) analysis. Compared with the two other
      molecular techniques, VNTR analysis was a simple, reliable and highly
      discriminatory method for fine typing of meningococcal isolates, showing a good
      correlation with the epidemiological data for the two outbreaks analysed.

PMID- 16961642
TI  - Characterisation of Neisseria meningitidis C:2b:P1.2,5 isolates in Poland.
AB  - This study aimed to characterise Neisseria meningitidis C:2b:P1.2,5 isolates from
      Poland, which have now become predominant among serogroup C isolates in this
      country. Overall, 44 isolates (25 invasive and 19 from contact carriers) were
      typed by whole-cell ELISA and pulsed-field gel electrophoresis. Additionally, the
      invasive isolates were analysed by multilocus sequence typing, which revealed
      that they all belonged to the ST-8 complex/cluster A4. The emergence of this
      clone in other countries has resulted in mass immunisation campaigns and has been
      associated with a higher level of decreased susceptibility to penicillin; however
      the present study detected only one isolate that was penicillin-non-susceptible.

PMID- 16961643
TI  - Treatment of bone and joint infections caused by Gram-negative bacilli with a
      cefepime-fluoroquinolone combination.
AB  - A 3-year retrospective study evaluated the effectiveness and safety of cefepime
      plus a fluoroquinolone for treating bone and joint infections caused by Gram
      negative bacilli (GNB) in 28 patients. Intra-operative cultures yielded primarily
      Pseudomonas spp. and Enterobacter cloacae. Full recovery (cure) was observed in
      79% of patients. There were no serious adverse effects and no resistant organisms
      were isolated. The results of the study confirmed the safety and effectiveness of
      cefepime combined with a fluoroquinolone for the treatment of bone and joint
      infections caused by Gram-negative bacilli.

PMID- 16961645
TI  - New phage type among methicillin-resistant Staphylococcus aureus associated with
      a local outbreak in Belgium during 2002.
AB  - In total, 150 methicillin-resistant Staphylococcus aureus (MRSA) isolates
      collected during 2002 from a general Belgian hospital were phage-typed at routine
      test dilution x 100. The majority (45%) belonged to phage group (J)*, while 10%
      were classified as a new phage type 29/(42E)/54/(D11)*. The isolates belonging to
      this new type carried the aac(6')-aph(2'') and the aph(3') aminoglycoside
      resistance genes and showed high-level resistance to oxacillin. Molecular typing
      revealed that they belonged to the multiresistant clonal pulsed-field gel
      electrophoresis (PFGE) type D8. PFGE group D, characterised as genotype ST228
      MRSA-I, has been present in Belgian hospitals since 1999.

PMID- 16961644
TI  - Implication of biofilm formation in the persistence of urinary tract infection
      caused by uropathogenic Escherichia coli.
AB  - Escherichia coli is the most frequent microorganism involved in urinary tract
      infection (UTI). Acute UTI caused by uropathogenic E. coli (UPEC) can lead to
      recurrent infection, which can be defined as either re-infection or relapse. E.
      coli strains causing relapse (n = 27) and re-infection (n = 53) were analysed. In
      vitro production of biofilm, yersiniabactin and aerobactin was significantly more
      frequent among strains causing relapse. Biofilm assays may be helpful in
      selecting patients who require a therapeutic approach to eradicate persistent
      biofilm-forming E. coli strains and prevent subsequent relapses.

PMID- 16961646
TI  - Evaluation of the CLSI cefoxitin 30-microg disk-diffusion method for detecting
      methicillin resistance in staphylococci.
AB  - Methicillin susceptibility of 415 staphylococcal isolates from Chinese hospitals
      was assessed using the CLSI disk-diffusion method with a cefoxitin 30-microg disk
      in comparison with an oxacillin 1-microg disk. PCR-based detection of mecA was
      the reference standard. The cefoxitin 30-microg disk performed with almost the
      same high level of accuracy as the oxacillin 1-microg disk in detecting
      methicillin resistance in Staphylococcus aureus. For coagulase-negative
      staphylococci (CoNS), the sensitivity of the cefoxitin 30-microg disk was 90.5%,
      compared with 83.4% for the oxacillin 1-microg disk. Confirmatory testing of
      isolates with borderline susceptibility and revision of the cefoxitin breakpoint
      are proposed in order to categorise CoNS more accurately.

PMID- 16961647
TI  - Investigation of suspected laboratory cross-contamination: interpretation of
      single smear-negative, positive cultures for Mycobacterium tuberculosis.
AB  - Restriction fragment length polymorphism (RFLP) analysis can be used to assess
      genetic relatedness of Mycobacterium tuberculosis isolates. This study reports a
      collaborative investigation of false-positive cultures for M. tuberculosis,
      suspected when the DNA fingerprint from an index case matched an
      epidemiologically improbable source case. RFLP analysis matched fingerprints in
      ten of 16 cases of suspected laboratory contamination to four separate smear
      positive sources that were processed on the same day in the same laboratory. All
      single smear-negative, positive cultures processed on the same day as smear
      positive specimens should be reviewed on a case-by-case basis to identify
      possible false-positive cultures.

PMID- 16961648
TI  - Fine needle aspiration cytology: a survey of current European practice.
AB  - Fine needle aspiration cytology (FNAC) is practised widely throughout Europe. The
      majority of countries have dedicated cytopathologists as well as
      histopathologists practicing cytology. Despite this, FNAC is performed mostly by
      clinicians and radiologists except in the larger centres with dedicated staff
      with a special interest in cytopathology. The advent of One-Stop diagnostic
      services and image-guided procedures are prompting further development of FNAC
      clinics where cytopathologists take their own samples, issue reports in the same
      clinical session and take extra material for ancillary tests to complete the
      diagnosis. The volume of FNAC work varies accordingly; in dedicated centres FNAC
      represents up to 80% of the workload whilst, in the majority of countries, it
      represents one quarter or less. Hence, the rate of inadequate FNAC varies widely,
      depending on the local sampling policies and the organ, but does not exceed 25%
      in any of the countries. The most sampled organs are breast and thyroid, followed
      by lymph nodes. Most countries have dedicated training in cytopathology for
      pathology trainees, the duration varying between 6 months and 2 years of the
      total training time. This discussion, focusing on European practices, highlights
      the heterogeneity of FNAC activity but also its success in many centres where it
      is practiced to a high standard, particularly in breast, thyroid and lymph node
      pathology. The relatively high rate of inadequate material in some centres
      reflects local policies and calls for greater uniformity of FNAC practice,
      particularly specimen sampling. To achieve this, the future direction should
      concentrate on specialist training, to include performing as well as interpreting
      FNAC, as part of the curriculum. Current emphasis on web-based training may not
      provide first hand experience of the FNAC procedure and should be supplemented by
      attending FNAC clinics and developing the technique to its full potential.

PMID- 16961649
TI  - Cytology is useful in breast screening: results and long-term follow-up of the
      Singapore Breast Screening Pilot Project.
AB  - OBJECTIVE: The Singapore Breast Screening Pilot Project (SBSPP) was embarked upon
      (1994-1997) to determine if mammography was useful in early breast cancer
      detection among Asian women. PATIENTS AND MEASUREMENTS: Of 28 231 women screened,
      fine needle aspiration cytology (FNAC) was performed in 232 individuals as part
      of the triple assessment. RESULTS: Absolute and complete sensitivities for the
      diagnosis of carcinoma were 46.7% and 82.2%, respectively, based on the results
      of FNAC. Specificity was 63.3%. The inadequate rate was 31%. Five women who were
      considered cancer-free on triple assessment and, in two cases open diagnostic
      biopsy during the SBSPP, subsequently developed breast cancer after a median
      follow-up of 6 years. CONCLUSION: Although our FNAC results compared relatively
      well with international standards, they reflect a small cohort, and may face
      additional difficulties in a larger programme.

PMID- 16961650
TI  - Mastopathic fibroadenoma of the breast: a pitfall of aspiration cytology.
AB  - OBJECTIVE: To assess the correlation between cytological diagnoses and
      histological subtypes of fibroadenoma (FA) and to clarify the cytological
      features of a specific group of FA displaying variable features similar to
      fibrocystic disease (mastopathic type, MFA), and to evaluate the significance of
      this subtype in cytological diagnosis. METHODS: A review of 141 cases of
      histologically proven FA was performed. We re-classified them into four subtypes
      according to Kinoshita's criteria [Jpn J Breast Cancer6 (1991) 377] and further
      selected 92 cases for which both fine needle aspiration (FNA) smears and
      histological specimens were available. Among them, 18 cases of MFA and their
      cytological smears were selected for the present study. RESULTS: There was
      significant correlation between MFA and cytological diagnosis of 'indeterminate'
      or 'suspicious for malignancy' (P < 0.01). Although no false-positive diagnosis
      was experienced in our series, 56% of the MFAs (10/18) had cytological diagnoses
      of indeterminate or were included in the category 'suspicious for malignancy'.
      Smears from MFA revealed high cellularity (9/18 smears had more than 10
      epithelial clusters each composed of more than 50 cells), presence of cellular
      discohesiveness (13/18, 72.2%), but only mild nuclear atypia (5/18, 27.8%).
      Anisonucleosis was present in fewer than half the cases and no apparent condensed
      chromatin was identified. CONCLUSION: We highlight the significance of
      subclassification of MFA in aspiration cytology of breast. MFA had a
      significantly higher chance of falling into the 'suspicious for malignancy' or
      'indeterminate' diagnostic category in aspiration cytology. It might be a
      diagnostic challenge for cytopathologist to identify this subtype of FA in FNA
      smears.

PMID- 16961651
TI  - FNA of breast fibroadenoma: observer variability and review of cytomorphology
      with cytohistological correlation.
AB  - OBJECTIVE: To determine the observer variability in reporting fibroadenoma of the
      breast by fine needle aspiration (FNA) and to review the cytomorphological
      features of the lesion with cytohistological correlation. METHODS: Retrospective
      analysis of FNA smears from 110 cases diagnosed as fibroadenoma of which surgical
      pathology follow-up was available in 33. Two pathologists were asked to
      categorize smears from 67 cases of breast lesions while blinded to the clinical
      finding as fibroadenoma, epithelial hyperplasia (usual and atypical) and
      malignant. All fibroadenoma (33) and cancer (15) cases were biopsy-proven. The
      same set of slides was re-circulated to one of the pathologists, and his first
      and second round results were compared. RESULTS: Pre-review cytohistological
      correlation was attained in 32 of 33 cases of fibroadenoma (97%). The overall
      agreement between the two observers was 87% [Kappa = 0.74, 95% confidence
      interval (CI) 0.72-0.76]. Cytohistological correlation was achieved in 26 of 33
      (79%) cases. Intra-observer agreement was 91% (Kappa = 0.82, 95% CI 0.89-0.93)
      with cytohistological correlation in 29 of 33 (87%) cases. Causes of diagnostic
      errors included marked dissociation, pleomorphism, poorly cellular smears from
      hyalinized fibrodenoma, lacational changes and apocrine metaplasia with cystic
      changes. Multinucleated giant cells were frequently encountered in FNA smears
      from fibroadenoma (31.8%), but in none of the lumpectomy specimens. Their
      histiocytic nature was suggested by immunohistochemistry. CONCLUSION: FNA was a
      highly sensitive method for the diagnosis of fibroadenoma. Current cytological
      criteria were reliable and gave high inter- and intra-observer reproducibility.

PMID- 16961652
TI  - Fine needle aspiration cytology of the thyroid: a comparison of 5469 cytological
      and final histological diagnoses.
AB  - OBJECTIVE: We evaluated the efficacy of fine needle aspiration cytology (FNAC) of
      the thyroid in a series of 5469 lesions with histological control and studied the
      causes of, and the possibility of reducing the limitations of the method.
      METHODS: FNAC was always performed by a pathologist under the guidance of a
      clinician, using a 22-gauge needle. Generally two aspirations were carried out,
      and usually four slides were obtained for each nodule; they were then stained
      with May-Grunwald-Giemsa and with Papanicolaou. The cytological diagnoses were
      classified in four groups: inadequate, benign, suspicious and malignant. RESULTS:
      We obtained a complete sensitivity of 93.4%, a positive predictive value of
      malignancy of 98.6%, and a specificity of 74.9%. At histological control, the
      cytological diagnosis of Hurthle cell neoplasm corresponded to a significantly
      higher incidence of malignant neoplasms than the diagnosis of non-Hurthle cell
      follicular neoplasm (32.1% versus 15.5%). There were 66 false-negative findings,
      the main cause of diagnostic error (24 cases) being failure to recognize the
      follicular variant of papillary carcinoma. The number of inadequate FNACs was low
      (4.2%). CONCLUSION: Our study confirmed the great efficacy of thyroid FNAC. A
      cytological diagnosis of Hurthle cell neoplasm should be considered an indicator
      of high risk. Awareness that failure to recognize the follicular variant of
      papillary carcinoma was the main problem in the interpretation of thyroid FNAC
      should lead to a decrease of false-negative diagnoses. The inadequate rate was
      very low, as it was the pathologist personally who performed the needle
      aspiration.

PMID- 16961653
TI  - Ultrasound-guided fine needle aspiration cytology in the diagnosis and management
      of thyroid nodules.
AB  - OBJECTIVE: To examine the accuracy of fine needle aspiration cytology (FNAC) in
      the diagnosis of thyroid nodules and compare the inadequacy rates for ultrasound
      guided and freehand FNAC. METHODS: A retrospective study of 434 patients with
      thyroid nodules who underwent diagnostic FNAC over a 2-year period. Cytological
      diagnoses have been compared with the histological assessment of resection
      specimens in 69 cases. RESULTS: The inadequacy rate was significantly lower from
      ultrasound guided FNAC (24/373 cases, 6.4%) than from freehand FNAC (8/61 cases,
      13.1%) (P = 0.043). Seventy-six percentage of patients had a non-neoplastic
      cytological diagnosis and, after multidisciplinary review, the patients were
      reassured and assigned to clinical follow-up. Sixty-seven patients had a
      resection for cytological appearances consistent with non-neoplastic disease (n =
      34), suspicious of follicular neoplasia (n = 23), or suspicious of malignancy (n
      = 10), and two patients had resections following inadequate cytology with
      ultrasound appearances suspicious of a neoplasm. The overall accuracy of FNAC
      analysis for malignancy was 97.0%, with sensitivity 83.3%, specificity 98.0%,
      positive predictive value 71.4% and negative predictive value 98.4%. The overall
      accuracy of FNAC analysis for the prediction of neoplasia was 97.5%, with
      sensitivity 80.5%, specificity 97.8%, positive predictive value 89.2% and
      negative predictive value 95.9%. Difficulties in cytological diagnosis were
      associated with lymphoid infiltrates and with degenerative changes in follicular
      adenomas. CONCLUSION: Ultrasound-guided FNAC has a significantly lower yield of
      inadequate aspirates than palpable FNAC. The ability of FNAC to predict neoplasia
      in 89% patients and to exclude neoplasia in 95.9% patients makes an important
      contribution to the multidisciplinary assessment of patients.

PMID- 16961654
TI  - Comparative cytomorphology of skin, lymph node, liver and bone marrow in patients
      with lepromatous leprosy.
AB  - OBJECTIVE: The aim of this study was to compare the cytological changes in skin,
      lymph nodes, liver and bone marrow in patients with lepromatous leprosy. METHODS:
      Skin lesion, lymph node, liver and bone marrow aspirates were analysed. May
      Grunwald-Giemsa (MGG) and Ziehl-Neelsen (Z-N) stains were employed. Comparative
      cytomorphology was studied. RESULTS: Twenty patients with lepromatous leprosy
      were studied. Lepra cells (LC) predominated in the skin aspirates of 12 patients
      with lepromatous leprosy (LL), lymphocytes accompanied LC in eight patients with
      borderline-lepromatous (BL) leprosy. Three patients of LL leprosy and two of BL
      leprosy in type 2 reaction additionally had numerous neutrophils. Two patterns of
      lymph node aspirates were seen: partial replacement with few LC in a reactive
      lymphoid background (10), complete replacement with either only LC or LC in a
      background of degenerating neutrophils (10), the latter a feature of type 2
      reaction. Liver aspiration was performed in seven patients and of bone marrow in
      eight patients. Occasional LC were present in five liver-aspirated patients,
      steatosis and Kupffer cell hyperplasia in four patients, and myelopoiesis in two
      patients. Bone marrow smears invariably had occasional LC and a relative increase
      in mature plasma cells; sea-blue histiocytes were seen in six patients.
      CONCLUSION: Lepra cells predominated in skin and lymph node aspirates with
      complete replacement. In comparison, liver, bone marrow and lymph node aspirates
      with partial replacement were dominated by a preponderance of cells native to
      these organs with only few or occasional LC.

PMID- 16961655
TI  - Diagnosing amyloid goitre with thyroid aspiration biopsy.
AB  - OBJECTIVE: The aim of the study was to evaluate the value of fine needle
      aspiration biopsy of the thyroid as a tool for diagnosing amyloid goitre and
      assess how amyloidosis affects thyroid tissue and thyroid function. METHODS:
      Clinical and laboratory evaluation of 50 patients with secondary systemic
      amyloidosis was done, and goitre was found in 38 of them. All 38 patients
      underwent thyroid aspiration biopsy. Tissue samples were stained with
      haematoxylin and eosin, May-Grunwald-Giemsa, crystal violet and Congo red.
      RESULTS: Of the 38 cases of amyloid goitre, 10 showed euthyroid sick syndrome,
      two showed primary hyperthyroidism, two showed hypothyroidism and one showed
      subacute thyroiditis. The serum levels of thyroid hormones and thyroid
      stimulating hormone were normal in the remaining patients. Thirty-five of the 38
      patients (92%) showed amyloidosis after thyroid aspiration. One of these patients
      had papillary carcinoma in addition to amyloid goitre. Ten patients underwent
      subtotal thyroidectomy, and one patient underwent total thyroidectomy after
      aspiration. Microscopic evaluation revealed that the thyroid parenchyma in all
      patients was largely replaced with amyloid and adipose tissue. CONCLUSION: Fine
      needle aspiration of the thyroid is a valuable and sensitive method for
      diagnosing amyloid goitre, especially because it is a safe and easily performed
      procedure. Further, amyloid goitre has no significant influence on thyroid
      function even when it causes extensive parenchyma replacement.

PMID- 16961656
TI  - The diagnostic value of on-site cytopathological evaluation and cell block
      preparation in fine-needle aspiration cytology of liver masses.
AB  - OBJECTIVE: The aims of this study were to evaluate the typing accuracy of
      conventional smear (CS), cell block (CB) preparations and combined use of both
      procedures (CS + CB) for the diagnosis of hepatic malignancies and to determine
      whether immediate on-site cytopathological evaluation improves the diagnostic
      yield of liver fine-needle aspiration cytology (FNAC). METHODS: Ultrasound-guided
      FNABs were performed on 323 consecutive cases with liver masses between December
      2002 and December 2004. Histologically and/or clinically correlated 167 cases
      were included in the study. Preliminary FNAB results, results of CS, CB, and
      combined use of CS and CB were compared regarding diagnostic sensitivity,
      specificity, and accuracy for the diagnosis of malignancy. Subtyping accuracies
      of different methods were also compared. RESULTS: The sensitivity of on-site
      cytopathological examination and CS were both 92.8%. The sensitivity of CS + CB
      was slightly better than that of CB (93.5% versus 84.8%). Specificity of all
      procedures was achieved 100%. Diagnostic accuracy of on-site cytopathological
      evaluation, CS, CB, and CS + CB were 93.9%, 93.9%, 87.2%, and 94.5%,
      respectively. A specific subtype diagnosis of malignant tumours could be rendered
      accurately on the basis of preliminary diagnosis in 71%, CS in 75.4%, CB in 78.3%
      and combined approach in 92% of cases. In terms of typing accuracy, 87.5% of
      HCCs, 93.2% of adenocarcinomas, 92.3% of neuroendocrine carcinomas, 100% of
      lymphomas and 100% of other malignant tumours were correctly subclassified in the
      final cytopathological diagnosis. The agreement between preliminary diagnosis and
      final cytopathological diagnosis was 77.2%. CONCLUSION: With use of on-site
      cytopathological evaluation and combined use of CS and CB, the diagnostic
      accuracy of liver tumours approaches 100% and also significantly improve
      diagnostic and subtyping accuracy of liver malignancies.

PMID- 16961657
TI  - Role of ancillary techniques in diagnosing and subclassifying non-Hodgkin's
      lymphomas on fine needle aspiration cytology.
AB  - Non-Hodgkin's lymphomas (NHL) are tumours of the lymphoid cells. During the
      process of development of lymphoid cells, neoplasia may evolve at any point.
      Neoplastic cells usually carry the imprint of cell of origin at the stage of
      origin. Various types of NHL may have similar morphology with wide variation in
      origin, immunophenotype and other biological features. Different ancillary
      laboratory techniques may help to overcome the limitations of morphology in this
      aspect. The commonly used ancillary techniques in lymphomas are
      immunocytochemistry (IC), flow cytometry, Southern blot (SB) technique,
      polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH). In
      addition, laser scanning cytometry (LSC) and DNA microarray technologies are in
      the research phase. Various laboratory techniques are used for immunophenotyping,
      demonstration of monoclonality, identification of chromosomal translocation,
      assessment of cell kinetics and expression of mRNA in the tumour cells. Flow
      cytometry helps in rapid immunophenotying of NHL and it has an added advantage
      over IC in recognizing the co-expression of CD markers. Fine needle aspiration
      cytology (FNAC) combined with flow immunophenotyping may help us to diagnose and
      subclassify certain NHLs, such as follicular lymphoma and mantle cell lymphoma,
      which were previously recognized as pure morphological entities. Loss of
      morphology is one of the important limitations of flow cytometry. LSC can
      overcome this limitation by studying morphology along with the immunophenotyping
      pattern of individual cells. Chromosomal changes in NHL can be identified by SB,
      PCR and FISH. Molecular diagnosis of NHL helps in diagnosis, subclassification,
      prognostic assessment and even in planning of therapy. DNA microarray is a
      relatively newer and promising technology. It gives information about the
      expression of several thousands of genes in a tumour in a single experiment. In
      the near future, FNAC combined with ancillary techniques may play a major role in
      diagnosis, subclassification and management of lymphomas.

PMID- 16961658
TI  - Cutaneous squamous cell carcinoma metastatic to chronic lymphocytic leukaemia:
      diagnostic potential of fine needle aspiration cytology.
AB  - OBJECTIVE: The phenomenon of cancer-to-cancer metastasis of cutaneous squamous
      cell carcinoma (SCC) and chronic lymphocytic leukaemia (CLL)/small lymphocytic
      lymphoma (SLL) is a rare event and only occasionally documented in the medical
      literature. METHODS: Two patients with SCC of the skin that were previously
      treated for CLL are presented. Both had palpable lymph nodes in the neck and fine
      needle aspiration cytology (FNAC) was performed to evaluate the pathological
      process. In addition, the literature on cutaneous SCC metastatic to CLL/SLL with
      special emphasis on the role of FNAC in this specific clinical situation was
      reviewed. RESULTS: On examination of the FNAC smear, cancer-to-cancer metastasis
      of cutaneous SCC to lymph node replaced by CLL was found. In one of the patients,
      light microscopy examination of the smear was complemented by immunostaining of
      atypical cells with cytokeratin antibodies and immunophenotyping of lymphoid
      cells by flow cytometry. In addition to our two patients, nine cases of cutaneous
      SCC metastatic to CLL/SLL have been reported in the literature, and in only one
      was the diagnosis made by FNAC. CONCLUSION: FNAC supported by ancillary
      immunocytological techniques could also be used in diagnosis of specific clinical
      situations such as cancer-to-cancer metastasis of the tandem of SCC-CLL/SLL.

PMID- 16961659
TI  - Thyroid tumour in a child previously treated for neuroblastoma.

PMID- 16961661
TI  - Cerebrospinal fluid findings in central neurocytoma.

PMID- 16961660
TI  - Abnormal glandular cells in a cervical smear.

PMID- 16961662
TI  - Cell cannibalism in ductal carcinoma of breast.

PMID- 16961663
TI  - Cytology of epithelioid sarcoma.

PMID- 16961664
TI  - Fine needle aspiration and core biopsy from a 43-year-old man with multiple
      abdominal masses.

PMID- 16961665
TI  - Cytological findings of a primitive neuroectodermal tumour presenting as a
      parotid mass.

PMID- 16961666
TI  - Metastatic lobular carcinoma of breast presenting on a routine cervical smear.

PMID- 16961667
TI  - Clinical aspects of parvovirus B19 infection.
AB  - Parvovirus B19 is a significant human pathogen that causes a wide spectrum of
      clinical complications ranging from mild, self-limiting erythema infectiosum in
      immunocompetent children to lethal cytopenias in immunocompromised patients and
      intrauterine foetal death in primary infected pregnant women. The infection may
      also be persistent and can mimic or trigger autoimmune inflammatory disorders.
      Another important clinical aspect to consider is the risk of infection through
      B19-contaminated blood products. Recent advances in diagnosis and pathogenesis,
      new insights in the cellular immune response and newly discovered genotypes of
      human parvoviruses form a platform for the development of modern therapeutic and
      prophylactic alternatives.

PMID- 16961668
TI  - Who should receive a statin these days? Lessons from recent clinical trials.
AB  - The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins are the
      most successful cardiovascular drugs of all time. By interrupting cholesterol
      synthesis in the liver, they activate hepatocyte low-density lipoprotein (LDL)
      receptors and produce consistent and predictable reductions in circulating LDL
      cholesterol with resulting reproducible improvements in cardiovascular risk by
      retarding or even regressing the march of atherosclerosis in all major arterial
      trees (coronary, cerebral and peripheral). Clinical trials have demonstrated
      their capacity not only to extend life, but also to improve its quality by
      retarding the progression of diabetes mellitus and chronic renal disease and by
      enhancing central and peripheral blood flow. They are amongst the most
      extensively investigated pharmaceutical agents in current clinical use. In
      cardiovascular end-point trials they have proven ability to help prevent that
      first and all important myocardial infarction and to reduce the likelihood of a
      recurrence in those who do succumb. They are equally effective in men and women
      of all ages and at all levels of cardiovascular risk, whether caused by
      hypercholesterolaemia, hypertension, cigarette smoking, diabetes mellitus or the
      metabolic syndrome. In addition, they improve the outlook of patients with
      familial hypercholesterolaemia whose LDL receptor function is deficient or
      defective; and all of this comes at minimal risk to the recipient. Their most
      important potential side effect is myopathy, which on very rare occasions may
      lead to rhabdomyolysis. Clinical experience shows that myopathic symptoms with
      creatine kinase levels raised to more than 10 times the upper limit of normal is
      seen in <0.01% of recipients and progression to fatal rhabdomyolysis because of
      renal failure has been recorded in only 0.15 cases per million prescriptions.
      Liver function abnormalities are also, rarely, seen. Again, the frequency of
      raised aspartate or alanine aminotransferase to more than three times the normal
      limit is encountered in no more than 1-2% of all treated patients and is
      completely reversible upon withdrawal of treatment. Progression to hepatitis or
      liver failure does not occur. This constellation of benefits with little side
      effect penalty has resulted in the comparison of statins with antibiotics in the
      global battle against cardiovascular disease.

PMID- 16961670
TI  - Breathlessness, phlegm and mortality: 26 years of follow-up in healthy middle
      aged Norwegian men.
AB  - OBJECTIVES: It is well known that pulmonary function is associated with all-cause
      and cardiovascular (CV) death. Less is known about the association between
      respiratory symptoms and mortality and whether such an association is independent
      of physical fitness. In this study, we assessed the association of breathlessness
      and productive cough with CV and all-cause mortality over 26 years. DESIGN:
      Prospective occupational cohort study. SETTING AND SUBJECTS: In 1972-75, 1999
      apparently healthy men aged 40-59 years were recruited to the study from five
      companies in Oslo, Norway. At study entry clinical, physiological and biochemical
      parameters including respiratory symptoms, spirometry, and an objective
      assessment of physical fitness were measured in all subjects, of whom 1,623 had
      acceptable spirometry. The data was analysed using Cox proportional hazards
      analysis, adjusting for age, lung function, physical fitness, and other possible
      confounders, with mortality until 2000. RESULTS: After 26 years (range 25-27),
      615 men (38%) had died, of whom 308 (50%) from CV deaths. In multivariable
      proportional hazards models, 'having phlegm winter mornings' [hazard ratio (HR)
      1.30, P = 0.01], 'breathlessness when hurrying/walking uphill' (HR 1.43, P =
      0.005) and combinations of the two symptoms remained significant predictors of
      all-cause mortality. None of six respiratory symptoms were significant predictors
      of CV mortality in multivariable models. CONCLUSIONS: Phlegm, breathlessness and
      combinations of them were associated with all-cause mortality, even after
      adjusting for physical fitness, known CV and other risk factors such as smoking,
      and lung function. The finding of an association also after adjustment for
      physical fitness is new. In contrast, none of the six respiratory symptoms
      individually or in combination were associated with CV mortality in multivariable
      analysis.

PMID- 16961669
TI  - Cognitive-behavioural stress management does not improve biological
      cardiovascular risk indicators in women with ischaemic heart disease: a
      randomized-controlled trial.
AB  - OBJECTIVES: Psychosocial factors, such as stress and vital exhaustion, are
      associated with an increased risk of cardiovascular events, and women report more
      psychosocial ill-being after an acute myocardial infarction than men. We have
      earlier shown that a cognitive-behavioural intervention in women with ischaemic
      heart disease (IHD) improved psychosocial well-being. In the present study, we
      tested the hypothesis that the improvement in psychosocial well-being is
      associated with an improvement in biochemical indicators of cardiovascular risk.
      DESIGN: Randomized-controlled trial in northern Sweden. SETTING: Outpatient care.
      SUBJECTS: Women with IHD were randomized to either a 1-year cognitive-behavioural
      stress management programme or usual care. Of the 159 women who completed the
      study, 77 were in the intervention group, and 82 in the control group.
      INTERVENTIONS: A 1-year cognitive-behavioural stress management programme versus
      conventional care. RESULTS: Group assignment was not found to be a determinant of
      waist circumference, high sensitive C-reactive protein (hs-CRP), fibrinogen, von
      Willebrand factor (vWF), plasminogen activator inhibitor type 1 (PAI-1) activity,
      tissue plasminogen activator (tPA) activity, tPA antigen, tPA-PAI-1 complex,
      leptin, or HOMA2 insulin resistance index (HOMA2-IR) at follow up. Changes in
      psychosocial variables were not associated with changes in any of the biological
      risk indicators. CONCLUSIONS: Even if our cognitive-behavioural stress management
      programme had effects on proximal targets, such as stress behaviour and vital
      exhaustion, we found no improvement in intermediate biochemical targets related
      to the metabolic syndrome and IHD. Our results challenge the proposition that the
      relationship between psychological well-being and biological cardiovascular risk
      indicators is a direct cause-effect phenomenon.

PMID- 16961671
TI  - Hyperthermia is a surrogate marker of inflammation-mediated cause of brain damage
      in acute ischaemic stroke.
AB  - The influence of temperature on the outcome observed in experimental models of
      ischaemic stroke has not been definitively proved in patients with stroke.
      Interleukin-6 (IL-6) acts as important endogenous pyrogen, and it is an important
      regulator of spontaneous body temperature during cerebral ischaemia. The
      objective of this study was to determine, during the acute phase of cerebral
      ischaemia, the potential relationship between proinflammatory cytokines and
      hyperthermia as a cause of larger cerebral infarcts. PATIENTS AND METHODS: We
      studied 229 patients with a first-ever acute hemispheric infarction admitted
      within the first 24 h from onset of symptoms. On admission, axillary temperature
      was recorded and blood chemistry studies and cranial computed tomography were
      performed. We classified body temperature into two groups: hyperthermia (>or=37.5
      degrees C) and normothermia (<37.5 degrees C). We determined proinflammatory
      markers [IL-6, tumour necrosis factor-alpha (TNF-alpha), intercellular adhesion
      molecule (ICAM-1) and vascular cellular adhesion molecule] on admission. Two
      outcome variables were evaluated: (i) infarct volume; (ii) Canadian Stroke Scale
      (CSS) at 3 months (CSS <or= 7 was considered poor outcome and CSS > 7 good
      outcome). RESULTS: Patients with hyperthermia had higher infarct volume [46.5
      (9.8-78.5) cm(3) vs. 19.1 (5.0-23.5) cm(3); P < 0.0001], as well as poor outcome
      at 3 months. Plasma levels of IL-6, TNF-alpha and ICAM-1 were significantly
      higher in the group of patients with hyperthermia than in the normothermic group.
      There was a significant correlation between body temperature on admission and
      infarct volume (r = 0.302; P < 0.0001), and between proinflammatory markers (IL-6
      and TNF-alpha) and infarct volume. A significant association was also found
      between proinflammatory markers (IL-6, TNF-alpha, and ICAM-1) and poor outcome.
      However, after adjustment for potential confounders, hyperthermia was not
      independently associated with either larger infarct volume or with poor outcome
      at 3 months. CONCLUSIONS: Inflammatory mediators play a role in acute ischaemic
      brain damage independently of hyperthermia.

PMID- 16961672
TI  - Effects of antihypertensive drug treatments on fracture outcomes: a meta-analysis
      of observational studies.
AB  - OBJECTIVE: To quantitatively pool findings from observational studies on the risk
      of fracture outcomes associated with exposure to five antihypertensive drug
      classes: angiotensin-converting enzyme (ACE) inhibitors, diuretics (in particular
      thiazide diuretics), beta-blockers, calcium-channel blockers and alpha-blockers.
      DESIGN: Systematic review and meta-analysis. DATA SOURCES: Publications listed in
      the MEDLINE, EMBASE and LILACS databases, the ISI proceedings, and bibliographies
      of retrieved articles. Sources were searched from the earliest possible dates
      through December 2005. REVIEW METHODS: We included case-control and cohort
      studies presenting relative risks and confidence intervals (CIs) for the
      association between exposure to antihypertensive agents and fracture outcomes.
      Data were extracted onto a standardized computer worksheet. Study quality was
      assessed using a 10-point questionnaire specific to case-control or cohort study
      design. RESULTS: Fifty-four studies were identified. Pooled estimates were
      computed using the software HEpiMA. The pooled relative risk (RR) of any fracture
      with use of thiazide diuretics was 0.86 (95% CI 0.81-0.92) and 1.14 (95% CI 0.84
      1.54) with use of nonthiazide diuretics. There was a statistically significant
      reduction of any fracture with use of beta-blockers, (RR 0.86, 95% CI 0.70-0.98).
      The one study with ACE inhibitor data showed protection (RR 0.81, 95% CI 0.73
      0.89). No significant associations were found between fractures and exposure to
      alpha-blockers or calcium-channel blockers. CONCLUSIONS: Thiazide diuretics and
      beta-blockers appear to lower the risk of fractures in older adults. However,
      these agents cannot be recommended as preventive therapies for fractures until
      data from randomized controlled trials have established their efficacy. Patients
      who use these inexpensive drugs as treatments for hypertension may also benefit
      from a reduction in fracture risk.

PMID- 16961673
TI  - Effects on mortality of abciximab in ST-elevation myocardial infarction treated
      with percutaneous coronary intervention including stent implantation.
AB  - OBJECTIVES: To investigate the effects of abciximab on mortality in ST-elevation
      myocardial infarction (STEMI) treated with percutaneous coronary intervention
      (PCI) including stent implantation. DESIGN: Meta-analysis of three selected
      randomized studies and analysis of data from the Swedish Coronary Angiography and
      Angioplasty Registry (SCAAR). SUBJECTS: Pooled data from randomized studies
      containing in total 1,736 patients undergoing PCI with stent implantation because
      of STEMI with duration between symptom and treatment <12 h, and 7,436 patients
      from SCAAR treated with PCI because of STEMI (52% treated with abciximab) in
      Sweden 2000-2004. RESULTS: Analyses of pooled data showed that abciximab was
      associated with a decreased risk of reinfarction [odds ratio (OR) 0.38] and
      urgent target vessel revascularization (OR 0.38) at 30 days. No effect was seen
      on mortality at 30 days or 6 months. Multivariate analysis of data from SCAAR
      showed that abciximab reduced the risk of death during 14 months of follow-up
      (hazard ratio 0.82). CONCLUSIONS: The results are encouraging and support the
      ACC/AHA and ESC recommendation to use abciximab in treatment of STEMI with PCI
      including stent implantation. Considering that the pooled results from previous
      trials showed no effect of abciximab on mortality and the registry part of the
      present study was observational, the results encourage carrying out new
      randomized studies of abciximab in STEMI treated with PCI, including stent
      implantation, with sufficient size and length of follow-up.

PMID- 16961674
TI  - Effectiveness of written guidelines on the appropriateness of thromboprophylaxis
      prescriptions for medical patients: a prospective randomized study.
AB  - OBJECTIVE: To assess the effectiveness of providing doctors with written
      thromboprophylaxis prescription aids based on current recommendations. DESIGN: A
      prospective trial of specific anticoagulant prescription forms: a 1-day survey
      before and after the intervention in each centre. SETTING: 30 Internal Medicine
      departments of Assistance Publique-Hopitaux de Paris. SUBJECTS: All inpatients
      were included, except those who were either admitted or discharged on the day of
      the survey, and those receiving curative anticoagulant treatment. INTERVENTIONS:
      The study included three parts: (i) a 1-day baseline survey; (ii) over the
      following 3-month period, departments were randomized into two groups: all
      practitioners in wards allocated to the intervention group were required to
      systematically use specific anticoagulant prescription forms, whilst doctors in
      the control group continued prescribing according to their usual practices and
      (iii) a 1-day postintervention survey. MAIN OUTCOME MEASURE: The proportion of
      prescriptions in accordance with the recommendations. RESULTS: 1,469 patients
      were included. The intervention produced a significant reduction in the frequency
      of over-prescriptions, from 25% to 14% of the patients who did not meet the
      guideline criteria (adjusted OR: 0.3; 95% CI: 0.1-0.8). Using specific forms did
      not improve under-prescription of anticoagulants. A little over 60% of the
      patients who met guideline criteria for thromboprophylaxis were prescribed
      anticoagulants in both intervention and control wards, either at baseline or
      after intervention. CONCLUSIONS: Multitargeted interventions using a variety of
      means and strategies should still be considered to improve prescriptions that may
      have a significant impact on health expenses and, most importantly, on patients
      outcomes.

PMID- 16961675
TI  - C-reactive protein, heart rate variability and prognosis in community subjects
      with no apparent heart disease.
AB  - OBJECTIVES: Increased C-reactive protein (CRP) and reduced heart rate variability
      (HRV) both indicate poor prognosis. An inverse association between HRV and CRP
      has been reported, suggesting an interaction between inflammatory and autonomic
      systems. However, the prognostic impact of this interaction has not been studied.
      We thus investigated the prognostic impact of CRP, HRV and their combinations.
      DESIGN: Population-based study. SUBJECTS: A total of 638 middle-aged and elderly
      subjects with no apparent heart disease from community. METHODS: All were studied
      by clinical and laboratory examinations, and 24-h Holter monitoring. Four time
      domain measures of HRV were studied. All were prospectively followed for up to 5
      years. RESULTS: Mean age was 64 years (55-75). During the follow-up, 46 total
      deaths and 11 cases of definite acute myocardial infarction were observed. Both
      CRP and three of four HRV measures were significantly associated with increased
      rate of death or myocardial infarction. In a Cox model with CRP >or=2.5 microg
      mL(-1), standard deviation for the mean value of the time between normal
      complexes <or=100 ms, and their combination, hazard ratio and 95% CI for subjects
      with both abnormalities was 3.20 (1.55-6.56), P = 0.0016, and for subjects with
      either abnormality 1.63(0.83-3.20), P = 0.15, after adjustment for conventional
      risk factors. The combination of CRP and other measures of HRV gave similar
      results. This indicates an interaction between CRP and HRV with a synergistic
      effect. CONCLUSIONS: The combination of CRP and HRV or heart rate (HR) predicts
      death and myocardial infarction with synergism, indicating interaction between
      inflammatory and autonomic systems with a prognostic significance.

PMID- 16961676
TI  - Evaluation of a primary care-oriented brief counselling intervention for obesity
      with and without orlistat.
AB  - OBJECTIVE: There is a significant need for an obesity treatment model suitable
      for the primary care environment. We examined the effectiveness of a brief
      counselling intervention alone, in combination with orlistat, and drug-alone in a
      12-month randomized-clinical trial at a medical school obesity centre. METHODS:
      Participants (N = 250) with body mass index (BMI) >or=27 were randomized. Changes
      in body weight, lipids, blood pressure and serum glucose were examined. Drug
      adherence and attendance were also evaluated. RESULTS: Completers analysis was
      conducted on 136 participants with data at baseline, 6 and 12 months and
      intention-to-treat analyses (ITT) for the total sample. Amongst completers,
      participants in the drug only (P = 0.012) and drug + brief counselling (P =
      0.001) groups lost more weight (mean +/- SD: -3.8 +/- 5.8 kg and -4.8 +/- 4.4 kg,
      respectively) than participants in the brief counselling only group at 6 months (
      1.7 +/- 3.3 kg), but there were no significant group differences at 12 months.
      ITT model results were similar to completers at 6 months and remained significant
      at 12 months, but the weight losses were more modest (<3 kg) for both groups
      receiving orlistat. For brief counselling alone, participants gained weight (1.7
      +/- 4.2 kg). Cardiovascular disease (CVD) parameter changes were negligible.
      CONCLUSIONS: Pharmacotherapy alone or combined with brief counselling resulted in
      modest weight losses that had minimal impact on cardiovascular parameters, but
      were greater than brief counselling alone. Whilst brief interventions and primary
      pharmacotherapy have been suggested as viable treatments for implementation in
      primary care settings, our study suggests that such minimal interventions provide
      minimal benefits.

PMID- 16961677
TI  - Dietetics - a changing profession.

PMID- 16961678
TI  - Validation and reproducibility of a semi-quantitative Food Frequency
      Questionnaire for use in elderly Swiss women.
AB  - OBJECTIVE: The principal aim of this study was to develop a Swiss Food Frequency
      Questionnaire (FFQ) for the elderly population for use in a study to investigate
      the influence of nutritional factors on bone health. The secondary aim was to
      assess its validity and both short-term and long-term reproducibility. DESIGN: A
      4-day weighed record (4 d WR) was applied to 51 randomly selected women of a mean
      age of 80.3 years. Subsequently, a detailed FFQ was developed, cross-validated
      against a further 44 4-d WR, and the short- (1 month, n = 15) and long-term (12
      months, n = 14) reproducibility examined. SETTING: French speaking part of
      Switzerland. SUBJECTS: The subjects were randomly selected women recruited from
      the Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture
      cohort study. RESULTS: Mean energy intakes by 4-d WR and FFQ showed no
      significant difference [1564.9 kcal (SD 351.1); 1641.3 kcal (SD 523.2)
      respectively]. Mean crude nutrient intakes were also similar (with nonsignifcant
      P-values examining the differences in intake) and ranged from 0.13 (potassium) to
      0.48 (magnesium). Similar results were found in the reproducibility studies.
      CONCLUSION: These findings provide evidence that this FFQ adequately estimates
      nutrient intakes and can be used to rank individuals within distributions of
      intake in specific populations.

PMID- 16961679
TI  - Differences in the quantitative and qualitative performance of a calcium-specific
      food frequency questionnaire across age and sex.
AB  - OBJECTIVE: To examine putative differences in the quantitative and qualitative
      performance of a food frequency questionnaire (FFQ) for assessing dietary calcium
      intake across age and sex in the Greek population. MATERIALS AND METHODS: A total
      of 351 children (189 girls and 162 boys, aged 11.9 +/- 1.2 years), 260 adults
      (192 women and 68 men, aged 29.6 +/- 2.7 years) and 390 elderly individuals (317
      women and 73 men, aged 68.6 +/- 4.6 years) were recruited. Estimates of calcium
      intake from the 30-item FFQ were compared with those from a multi-pass 24-h
      recall. RESULTS: The FFQ significantly underestimated mean calcium intake in all
      age groups and both sexes (P < 0.05). The magnitude of underestimation, however,
      was greater in adults (-207 +/- 344 mg day(-1)), less in the elderly (-137 +/-
      310 mg day(-1)) and even less in children (-74 +/- 340 mg day(-1); P < 0.025),
      with no differences between sexes. Calcium intakes by the two methods were
      positively and significantly correlated in all study groups (r = 0.536-0.739, P <
      0.001). Cohen's weighted kappa statistic ranged from 0.39 to 0.57, indicating
      moderate agreement between the two methods. The 95% limits of agreement were
      comparably wide across age and sex (boys: -762, 585 mg day(-1); girls: -747, 624
      mg day(-1); adult men: -972, 505 mg day(-1); adult women: -867, 412 mg day(-1);
      elderly men: -858, 486 mg day(-1); elderly women: -732, 480 mg day(-1)). A
      significant association between age, sex and the classification of individuals as
      true/false positive/negative was detected (P < 0.001), implying that sensitivity,
      specificity, positive and negative predictive values of the FFQ were not
      independent of the age and sex of the participants. Gross misclassification by
      the FFQ ranged from 0% to 4.2%, whereas 75.3-87.3% of the subjects were correctly
      classified. In this respect, the FFQ performed similarly across the study groups
      (P = 0.065). Without controlling for age, however, gross misclassification
      appeared to be higher in females than in males (3.2% versus 0.7%, respectively, P
      = 0.048). CONCLUSIONS: There may be several significant differences in the
      quantitative and qualitative performance of a calcium-specific FFQ across age and
      sex. This should be taken into account when attempting to evaluate dietary
      calcium intake in men and women or in different age groups, as some of the
      differences between study groups may actually be due to the different response of
      these groups to the FFQ.

PMID- 16961680
TI  - Unidentified under-nutrition: dietary intake and anthropometric indices in a
      residential care home population.
AB  - BACKGROUND: Research investigating the nutritional status of older people in
      residential care homes is scant. OBJECTIVE: To determine the anthropometric
      measures and dietary intakes of older people in this setting as a basis for
      future intervention studies. METHODS: Dietary intake was assessed using 3-day
      weighed food records, nutritional status was evaluated using anthropometric
      measurements (knee height to predict standing height, and body weight). Catering
      provision was assessed using a computer-based menu assessment tool (CORA).
      RESULTS: Mean body mass index (BMI) for the 34 participants was 22.2 kg m(2)
      (range 14.5-34.4). Six participants (17.6%) had a BMI < or =18.5 kg m(2) with a
      further seven identified as having a BMI >18.5 but <20 kg m(2). Only two subjects
      with BMI <18.5 kg m(2) were prescribed oral supplements. In both men and women,
      recorded mean energy intakes were below current estimated average requirements by
      24% and 22% respectively. CONCLUSION: Despite adequate food provision, under
      nutrition was prevalent and, in the majority of cases, unidentified and
      untreated. A larger study is warranted to investigate whether improved
      nutritional intake is achievable through dietary modification. These data
      indicate that a sample size of around 60, with 90% power and at the 5%
      significance level, is required to detect a difference of 1674 kJ between groups
      of residents in an intervention study following a cluster randomized design.

PMID- 16961681
TI  - One year follow-up of overweight and obese hypertensive adults following
      intensive lifestyle therapy.
AB  - OBJECTIVE: To examine the long-term effect on weight maintenance and dietary
      habits of participants in a clinical trial for weight loss. SETTING: Community
      based residents living in Maryland. PARTICIPANTS: Forty-four hypertensive,
      overweight adults who participated in a randomized clinical trial of weight loss.
      Participants were randomized to an intensive 'lifestyle' intervention or a
      'monitoring' group. MAIN OUTCOME MEASURES: Weight, self-reported current intake
      of fat and fruit/fibre and self-reported barriers to maintain weight loss were
      assessed 1 year after the completion of the Diet, Exercise and Weight-loss
      Intervention Trial (DEW-IT) trial. ANALYSIS: t-tests were used to compare groups
      for differences in continuous variables and chi-square tests were used to compare
      groups for categorical variables. RESULTS: Fourty-two of the 44 DEW-IT subjects
      participated in the follow-up study. Overall, 55% (12/19) of the lifestyle
      intervention group remained at or below their baseline weight at 1 year, compared
      with 48% (11/23) of the monitoring group (P = 0.32). However, during that year,
      95% (18/19) of the lifestyle intervention group and 52% (12/23) of the monitoring
      group gained weight from the end of the study. Both groups reported similar
      intake of fruits/vegetables (servings day(-1)), dietary fibre (g day(-1)) and fat
      (g day(-1)). CONCLUSIONS AND IMPLICATIONS: The majority of participants who lost
      weight during the trial regained weight during the course of 1 year. A successful
      intensive 2-month programme of lifestyle modification (DEW-IT) was ineffective
      for long-term maintenance of weight loss.

PMID- 16961682
TI  - The impact of percutaneous endoscopic gastrostomy feeding upon daily life in
      adults.
AB  - BACKGROUND: The provision of home enteral tube feeding in adults has increased in
      the UK. This study explored how percutaneous endoscopic gastrostomy (PEG) feeding
      impacts on daily lives of adult patients, from the patients' and carers'
      perspectives. METHODS: A semi-structured interview approach was developed to
      obtain participants' views of the impact of living with a PEG. A cross-sectional
      qualitative purposive sampling design was employed. Thirty-four semi-structured
      interviews were conducted (15 adult patients and 19 carers) and data were
      analysed descriptively and thematically. RESULTS: Difficulties arising from PEG
      feeding included vomiting, diarrhoea, infection of the PEG site and leakage. The
      key issues that emerged included relief of pressure to consume an oral diet,
      disturbed sleep, restricted ability to go out, restricted choice of clothing,
      difficulties finding a place to feed, missing being able to eat and drink, social
      occasions, negative attitudes of others towards feeding and the burden placed on
      family members. CONCLUSIONS: The key themes that emerged from participants were
      diverse and highlight a need for increased social support for both patients and
      their carers, planned on an individual basis.

PMID- 16961683
TI  - An evaluation of renal inpatient meals against Renal Nutrition Group standards.
AB  - BACKGROUND: The Renal Nutrition Group (RNG) of the British Dietetic Association
      has developed standards for the nutritional composition of meals provided to
      renal patients in hospital. However, no data are available as to whether these
      are achievable. The purpose of this study was to determine whether renal
      inpatient meals can meet the standards set by the RNG. METHOD: A prospective 10
      day weighed food analysis of hospital meals provided to renal patients was
      undertaken. Two sample meals were analysed at each mealtime to include (1) the
      most energy dense choice and (2) the most frequent patient choice (FPC). RESULTS:
      Energy dense choice meals achieved the standard for protein provision on 90% of
      days, but provided too little energy on 100% of days (for men) and on 30% of days
      (for women). Although daily standards for potassium were met on 70% of days,
      those for sodium and phosphate were exceeded. FPC meals met the daily standards
      for potassium, sodium and phosphate on at least 80% of days, but provided too
      little protein on 40% of days and too little energy on 100% of days (for men and
      women). CONCLUSION: The majority of hospital meals fail to meet the RNG
      standards. Problems exist in providing sufficient energy and protein whilst
      restricting sodium, potassium and phosphate.

PMID- 16961684
TI  - Home delivery of dietary products in inherited metabolic disorders reduces
      prescription and dispensing errors.
AB  - In the UK, for patients with inherited metabolic disorders (IMD) the traditional
      system for acquiring essential dietary products [patient prompted prescriptions
      generated by a medical general practitioner (GP) and dispensed by a chemist] is
      problematic. OBJECTIVE: To investigate the efficacy of a home delivery service
      (HDS) for essential dietary products (EDP) (i.e. protein substitutes, milk
      replacements, energy and vitamin and mineral supplements) for subjects with IMD,
      particularly examining any prescription and dispensing errors, metabolic control
      and consumer satisfaction. METHODS: A prospective, controlled, home delivery
      trial for EDP was conducted in patients with IMD for 12 months. Sixty-two
      patients with IMD [50 with phenylketonuria (PKU); 12 with other IMD: aged 6
      months-30 years] were recruited. Thirty subjects used a monthly HDS (Homeward:
      Nutricia) to receive EDP, 32 remained on the traditional system. Each month, the
      HDS checked home stock levels of EDP, obtained their prescriptions directly from
      GP's, and then delivered them to the subjects' homes. An independent researcher
      completed monthly telephone interviews with patients/parents about any EDP
      prescription errors or delay in receipt. RESULTS: Incorrect protein substitute
      was dispensed once by the HDS compared with nine subjects who had 12 errors in
      the control group (P = 0.01); incorrect flavours of protein substitute were
      dispensed to the home delivery group once compared with eight subjects getting 11
      errors via the chemist (P = 0.03). The HDS delayed delivery of protein substitute
      for one subject on three occasions compared with 39 occasions in 16 subjects via
      the chemist (P = 0.001). In patients with PKU, plasma phenylalanine control
      deteriorated in the control group (P < 0.05) but not in the HDS group.
      CONCLUSIONS: The long-term use of a HDS for EDP in IMD is safer, effective and
      more reliable than conventional systems.

PMID- 16961685
TI  - Acculturation and education level in relation to quality of the diet: a study of
      Surinamese South Asian and Afro-Caribbean residents of the Netherlands.
AB  - BACKGROUND: To consider the changes in overall diet quality following migration
      we examined the associations of acculturation variables and education level with
      diet in Surinamese South Asian and Surinamese Afro-Caribbean origin on the one
      hand, and ethnic Dutch residents of the Netherlands on the other. Surinam is a
      former Dutch colony in South America. METHODS: We randomly selected men and women
      aged 35-60 years: ethnic Dutch, n = 552; South Asian, n = 306; Afro-Caribbean, n
      = 660. Intakes of fruit, vegetables, red meat, fish, vegetable oils, breakfast
      and salt were measured using a short questionnaire that formed the basis for a
      'diet quality indicator' score. Highest education was measured and acculturation
      of the Surinamese groups was assessed by age at migration, number of resident
      years and a scale measure of social contacts with ethnic Dutch. RESULTS: Compared
      with ethnic Dutch, both Surinamese groups scored higher on overall diet quality
      (P < or = 0.001) but some aspects of diet (breakfast and salt use) were less
      prudent. Education was positively associated with diet quality in ethnic Dutch (P
      < or = 0.01), but not consistently so in Surinamese. Associations with social
      contact with ethnic Dutch varied for different quality aspects of the diet.
      Residence duration (mean = 22 years) and age at migration (mean = 21 years) were
      not associated with diet. CONCLUSIONS: A greater degree of acculturation does not
      necessarily lead to a less healthful diet in migrants. In addition, the
      association of education level with diet may differ for migrant groups. The diet
      of migrants differ from host populations, suggesting that migrant groups should
      be considered in the development of nutrition health promotion activities.

PMID- 16961689
TI  - A mechanical perspective on intestinal tone and gas motion.

PMID- 16961690
TI  - Advances in ontogeny of the enteric nervous system.
AB  - The neurons and glia that comprise the enteric nervous system (ENS), the
      intrinsic innervation of the gastrointestinal tract, are derived from vagal and
      sacral regions of the neural crest. In order to form the ENS, neural crest
      derived precursors undergo a number of processes including survival, migration
      and proliferation, prior to differentiation into neuronal subtypes, some of which
      form functional connections with the gut smooth muscle. Investigation of the
      developmental processes that underlie ENS formation has progressed dramatically
      in recent years, in no small part due to the attention of scientists from a range
      of disciplines on the genesis of Hirschsprung's disease (aganglionic megacolon),
      the major congenital abnormality of the ENS. This review summarizes recent
      advances in the field of early ENS ontogeny and focuses on: (i) the
      spatiotemporal migratory pathways followed by vagal and sacral neural crest
      derived ENS precursors, including recent in vivo imaging of migrating crest cells
      within the gut, (ii) the roles of the RET and EDNRB signalling pathways and how
      these pathways interact to control ENS development, and (iii) how perpendicular
      migrations of neural crest cells within the gut lead to the formation of the
      myenteric and submucosal plexi located between the smooth muscle layers of the
      gut wall.

PMID- 16961691
TI  - Gastro-oesophageal reflux of liquids and gas during transient lower oesophageal
      sphincter relaxations.
AB  - Some transient lower oesophageal sphincter relaxations (TLOSRs) are accompanied
      by gastro-oesophageal reflux and others are not. We aimed to investigate what
      factors determine the occurrence and type of reflux during TLOSRs. In 12 healthy
      subjects prolonged high-resolution manometry was performed. Reflux was detected
      using pH-impedance monitoring. A total of 219 TLOSRs were detected; no
      differences were observed between the duration of TLOSRs with liquid-containing
      reflux (20.2 +/- 1.0 s), gas reflux (17.0 +/- 1.0 s) and no reflux (19.0 +/- 1.0
      s). Trans-sphincteric pressure gradient was similar in TLOSRs with liquid reflux
      (1.6 +/- 0.1 kPa), gas reflux (1.5 +/- 0.1 kPa) and no reflux (1.7 +/- 0.3 kPa).
      Prevalence, duration and amplitude of oesophageal pre-contractions and
      sphincteric after-contractions were not different for TLOSRs with and without
      reflux. The total number of TLOSRs decreased significantly from 8.2 +/- 0.8 in
      the first to 5.7 +/- 0.5 in the second and 4.4 +/- 0.6 in the third 70-min
      recording period. The number of TLOSRs accompanied by liquid-containing reflux
      decreased from 4.7 +/- 0.9 to 3.0 +/- 0.4 to 1.6 +/- 0.4, while the numbers of
      TLOSRs with gas reflux remained unchanged (2.1 +/- 0.6-2.1 +/- 0.7-2.2 +/- 0.6).
      Besides, time after the meal, no differences were observed in the characteristics
      of TLOSRs with and without gastro-oesophageal reflux. We conclude that factors,
      other than TLOSR characteristics, are important of whether or not a TLOSR is
      reflux-related.

PMID- 16961692
TI  - Regional gastric emptying abnormalities in functional dyspepsia and gastro
      oesophageal reflux disease.
AB  - To characterize proximal and distal stomach emptying in functional dyspepsia (FD)
      and gastro-oesophageal reflux disease (GORD). Eighty-three patients underwent
      gastric emptying (GE) scintigraphy and symptom scoring for the evaluation of
      upper gastrointestinal symptoms and were divided into three groups: FD (n = 25),
      GORD (n = 20) and FD + GORD (n = 38). Total, proximal and distal gastric
      retention were determined scintigraphically and compared with normal controls.
      Delayed total GE was observed in each subgroup: FD (56%), GORD (45%) and FD +
      GORD (55%). Greater proximal gastric retention was observed after meal ingestion
      in GORD compared to FD. Greater distal gastric retention was observed in FD and
      FD + GORD but it was only mild in GORD. Nausea, vomiting, early satiety,
      distention and regurgitation were associated with proximal gastric retention
      whereas there was no symptom associated with distal gastric retention. Multiple
      regression demonstrated total gastric retention at 30 min and 1 h was positively
      correlated with regurgitation whereas early proximal gastric retention was
      positively correlated with regurgitation and negatively correlated with nausea.
      Selective abnormalities of proximal and distal stomach emptying were demonstrated
      in GORD and FD. GORD and FD symptoms were associated with proximal gastric
      retention suggesting that proximal stomach motor function may be important in the
      pathogenesis of symptoms associated with these disorders.

PMID- 16961693
TI  - Intestinal tone and gas motion.
AB  - The intestine propels and evacuates large gas loads without detectable phasic
      contractions by manometry. We hypothesized that intestinal gas motion is produced
      by changes in gut tone and capacitance. In 13 healthy subjects, changes in
      duodenal tone were measured by a barostat during continuous perfusion of lipids
      (Intralipid, 1 kcal min(-1)) into the duodenum for 60 min. In separate groups,
      the effects of jejunal gas infusion (N2, CO2 and O2 in venous proportions at 12
      mL min(-1) starting after 15 min lipid perfusion) and sham infusion were tested.
      Gas outflow was collected continuously via an intrarectal cannula. Duodenal lipid
      perfusion produced a rapid duodenal relaxation (volume increased by 48 +/- 18%; P
      < 0.01 vs basal). Gas infusion increased gas evacuation (184 +/- 59 mL), and this
      was associated with a tonic contraction of the duodenum (R = 0.86; P < 0.01) that
      completely reverted the lipid-induced duodenal relaxation (volume decreased by 42
      +/- 13%; P < 0.05). During sham infusion only 52 +/- 28 mL of gas were evacuated
      (P < 0.05 vs gas infusion), and the duodenum remained relaxed due to the effect
      of lipids (0 +/- 1% volume reduction; ns). In conclusion, intestinal gas
      propulsion and clearance is associated with a tonic contraction of the gut wall
      and reduced gut capacitance.

PMID- 16961694
TI  - Effect of female sex hormone supplementation and withdrawal on gastrointestinal
      and colonic transit in postmenopausal women.
AB  - Females are disproportionately affected by constipation, which is often
      aggravated during pregnancy. Bowel function also changes during the luteal phase
      of the menstrual cycle. The aim was to compare the effects of acute
      administration of female sex steroids on gastric emptying, small bowel transit
      and colonic transit in healthy postmenopausal subjects. A second aim was to
      determine whether withdrawal of the hormones was associated with a change in
      transit. Forty-nine postmenopausal females were randomized to receive for 7 days
      400 mg day(-1) micronized progesterone, 0.2 mg day(-1) oestradiol, combination of
      the two, or placebo. Treatment groups were balanced on age. Participants
      underwent whole gut transit measurement by scintigraphy using a 99m-labeled
      technetium-egg meal and 111-labeled indium-charcoal via a delayed-release
      capsule. Transit measurement was repeated after withdrawal of the study
      medications. The primary endpoints were ascending colon (AC) emptying half-life
      time (t1/2) and colonic geometric centre (GC) at 24 h. Secondary analysis
      variables were GC at 4 and 48 h, gastric emptying t1/2 and colonic filling at 6
      h. There was a significant overall effect of progesterone on colonic transit with
      shorter AC emptying t1/2 and significantly greater colonic GC at 48 h. No transit
      endpoints were altered by oestradiol or combined hormonal treatment relative to
      placebo. Oestradiol and progesterone resulted in looser stool consistency.
      Withdrawal of the hormone supplement was not associated with significant
      alteration in transit. Micronized progesterone does not retard colonic transit in
      postmenopausal females.

PMID- 16961695
TI  - The influence of the novel 5-HT1A agonist R137696 on the proximal stomach
      function in healthy volunteers.
AB  - As fundic dysaccommodation represents one of the pathophysiological mechanisms
      underlying functional dyspepsia, gastric relaxant agents may serve as a new
      treatment of this disorder. Previous studies have suggested the involvement of
      5HT1 receptors in the control of gastric tone. Our aim was to study the effect of
      R137696, a novel 5HT1A agonist, on fundus sensorimotor function in healthy
      volunteers. The effect of single oral doses (1-2 mg) R137696 was evaluated in a
      double-blind, placebo-controlled manner on fasting fundic volume, visceral
      perception, distension-evoked symptoms and fundic compliance in 21 healthy male
      subjects. R137696 increased the proximal stomach volumes in a dose-dependent
      manner. Distention-evoked symptoms or distention and discomfort threshold were
      not altered by R137696. A logistic regression model, characterizing the
      relationships between the volume and the visual analogue scale score for
      dyspeptic symptoms (nausea, fullness, discomfort, pain and satiety) as a
      sigmoidal curve, revealed that R137696 had no effect on distension-induced
      discomfort, fullness, pain and satiety compared to placebo. R137696 relaxes the
      gastric fundus in fasting conditions but has no effect on distension-evoked
      dyspeptic symptoms in healthy volunteers.

PMID- 16961696
TI  - The nocturnal jejunal migrating motor complex: defining normal ranges by study of
      51 healthy adult volunteers and meta-analysis.
AB  - Interdigestive human small bowel motility is characterized by the migrating motor
      complex (MMC). The aims of this study were to: (i) establish the normal range of
      variables of the nocturnal jejunal MMC and (ii) incorporate these data in a
      subsequent meta-analysis. Eighty-one recordings were performed by prolonged (24
      h) ambulatory manometry in 51 subjects in two centres. Quantitative analysis was
      undertaken of 419 Phase III and 332 Phase II episodes. Adjusted mean values of
      seven variables were calculated using a mixed-effects model. Meta-analysis of
      pooled published data to generate a reliable 95% reference range was also
      performed. Adjusted mean values and confidence intervals are presented for all
      seven variables. Intrasubject variances were large in comparison with
      intersubject. Meta-analysis of 19 studies (356 pooled patients) meeting inclusion
      criteria produced wide reference ranges. At least five such ranges are useful for
      the detection of abnormality in the individual. This is the largest study of
      normal volunteers presented to date, with ranges for many variables produced
      using appropriate statistical methodology. A model for definition of abnormality
      has been proposed. We recommend that these data may be used by investigators in
      this field as a complement to other existing indicators of small bowel
      dysmotility.

PMID- 16961697
TI  - Hyperexcitability of convergent colon and bladder dorsal root ganglion neurons
      after colonic inflammation: mechanism for pelvic organ cross-talk.
AB  - Clinical studies reveal concomitant occurrence of several gastrointestinal and
      urologic disorders, including irritable bowel syndrome and interstitial cystitis.
      The purpose of this study was to determine the mechanisms underlying cross-organ
      sensitization at the level of dorsal root ganglion (DRG) after acute and subsided
      gastrointestinal inflammation. DiI (1,1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate) and Fast Blue were injected into the
      distal colon and urinary bladder of male rats, respectively. Convergent DRG
      neurons were found in L1-L3 and L6-S2 ganglia with an average distribution of 14%
      +/- 2%. The resting membrane potential (RMP) of cells isolated from upper lumbar
      (UL) ganglia was -59.8 +/- 2.7 mV, whereas lumbosacral (LS) neurons were more
      depolarized (RMP = -49.4 +/- 2.1 mV, P < or = 0.05) under control conditions.
      Acute trinitrobenzene sulfonic acid (TNBS) colitis (3 days) decreased voltage and
      current thresholds for action potential firing in LS but not UL convergent
      capsaicin-sensitive neurons. This effect persisted for 30 days in the absence of
      overt colonic inflammation. The current threshold for action potential (AP)
      firing in UL cells was also decreased from 165.0 +/- 24.5 pA (control) to 85.0 +/
      19.1 pA at 30 days (P < or = 0.05), indicating increased excitability. The
      presence of a subpopulation of colon-bladder convergent DRG neurons and their
      persistent hyperexcitability after colonic inflammation provides a basis for
      pelvic organ cross-sensitization.

PMID- 16961698
TI  - Involvement of cannabinoid receptors in inflammatory hypersensitivity to colonic
      distension in rats.
AB  - Activation of cannabinoid CB1 and CB2 receptors is known to attenuate nociception
      and hyperalgesia in somatic inflammatory conditions. The aim of this study was to
      determine whether cannabinoids modulate colonic sensitivity in basal and
      inflammatory conditions. The effects of CB1 and CB2 receptor agonists and
      antagonists on the abdominal contractile response to colorectal distension (CRD)
      in basal conditions and after 2,4,6-trinitrobenzenesulphonic acid-induced colitis
      were investigated. As previously described, colitis triggered a hypersensitivity
      to CRD. In basal conditions, both CB1 (WIN 55212-2) and CB2 (JWH 015) agonists
      reduced the abdominal response to CRD at a dose of 1 mg kg(-1), i.p. Both
      compounds were active at a lower dose (0.1 mg kg(-1)) abolishing the
      hypersensitivity induced by colitis. Administered alone, CB1 (Rimonabant) and CB2
      (SR 144528) receptor antagonists (10 mg kg(-1)) had no effect on basal
      sensitivity. In contrast, the CB1, but not the CB2, receptor antagonist enhanced
      colitis-induced hyperalgesia. It is concluded that colonic inflammation enhances
      the antinociceptive action of CB1 and CB2 receptor agonists, and activates an
      endogenous, CB1 receptor mediated, antinociceptive pathway.

PMID- 16961699
TI  - Objective investigation of the sleep-wake cycle in adults with intellectual
      disabilities and autistic spectrum disorders.
AB  - BACKGROUND: Disturbances in circadian rhythm functioning, as manifest in abnormal
      sleep-wake cycles, have been postulated to be present in people with autistic
      spectrum disorders (ASDs). To date, research into the sleep-wake cycle in people
      with ASDs has been primarily dependant on third-party data collection. METHOD:
      The utilization of non-invasive objective recording technologies such as
      actigraphy permits investigation of both sleep and circadian rhythm functioning
      in people with ASDs, together with the collection of data on daytime activity.
      RESULTS: Data were collected from 31 participants with intellectual disabilities
      living in supported community-based residential provision aged between 20 and 58
      years, of whom 14 had an ASD. Analysis indicated that there were no significant
      differences in sleep patterns and circadian rhythm function between those
      participants with an ASD and those without. CONCLUSIONS: The mean scores of the
      participants as a whole indicated abnormalities in the two key circadian rhythm
      parameters of interdaily stability and intradaily variability. The implications
      of these findings for both clinical practice and theory are discussed.

PMID- 16961700
TI  - Prevalence of gastrointestinal disorders in adult clients with pervasive
      developmental disorders.
AB  - BACKGROUND: In clients with pervasive developmental disorders (PDD), some authors
      have noticed the presence of gastrointestinal disorders and behavioural
      disorders. An augmented prevalence of different histological anomalies has also
      been reported. The aim of our study is to highlight the prevalence of
      gastrointestinal disorders in this adult with PDD sample and to demonstrate the
      importance of accurate evaluation of gastrointestinal disorders in clients with
      PDD. METHODS: The present comparative study involved 118 clients. Our research
      was motivated by the clinical observation that behavioural disorders sometimes
      disappeared with administration of anti-gastric acid or anti-ulcerous
      medications. It focused on two samples of clients with intellectual disability -
      those with associated PDD and those without. The presence of gastrointestinal
      disorders was assessed retrospectively on the basis of hospital records. RESULTS:
      The prevalence of gastrointestinal disorders reported in clinical files was 48.8%
      in clients with PDD, as compared with 8.0% in non-PDD clients (P < 0.00001).
      CONCLUSION: Gastrointestinal disorders, and especially gastro-oesophageal reflux,
      if neglected, may contribute to behavioural disorders in PDD clients. Moreover,
      gastrointestinal disorders may be considered as a feature of PDD. We highlight
      the fact that somatic disorders may coexist in persons with PDD.

PMID- 16961701
TI  - Comprehensive health assessments during de-institutionalization: an observational
      study.
AB  - BACKGROUND: People with intellectual disability (ID) leaving institutions pass
      through a transition stage that makes them vulnerable to inadequate health care.
      They enter into community care under general practitioners (GPs) who are often
      untrained and inexperienced in their needs. Specifically designed health reviews
      may be of assistance to both them and their new GPs as they go through that
      phase. METHODS: This research aimed to investigate the effectiveness of a
      specially designed health review, the comprehensive health assessment program
      (CHAP) health review, in a group of adults as they transitioned out of the care
      of the last institution for people with ID in Tasmania. There were 25 residents
      reviewed by their GPs. RESULTS: The CHAP reviews picked up a number of health
      conditions and stimulated health promotion activities. Some of the findings were:
      a high number of abnormal Body Mass Indexes (19/23), immunizations given (13/23),
      vision impairment reported (2/23), mental health issues recorded (4/23) and skin
      abnormalities described (17/23). There were 22 referrals made to other health
      professionals (Australian Hearing Service 4, dentists 3, optometrists 3,
      psychiatrists 2, neurologists 2, ophthalmologist 1, urologist 1, ultrasound 1,
      mammogram 1, family planning 1, physiotherapist 1, continence nurse 1 and
      respiratory physician 1). These were in addition to various requests for
      pathology. CONCLUSIONS: The CHAP health review was effective in identifying a
      number of health issues in the population of people with ID as they transitioned
      out of institutional care into the general community.

PMID- 16961702
TI  - Literacy achievement of children with intellectual disabilities and differing
      linguistic backgrounds.
AB  - BACKGROUND: The aim of the present study was to examine the literacy achievement
      of 10- to 12-year-old native and non-native children with intellectual
      disabilities (ID) living in the Netherlands. An intriguing question within this
      context was whether the second language learning non-native children with ID
      would show a double disadvantage when compared with their monolingual Dutch peers
      with no ID. METHODS: Dutch literacy scores in the domains of word decoding,
      vocabulary, syntax and text were therefore compared for: (1) intellectually
      disabled native Dutch children; (2) intellectually disabled non-native children;
      (3) normally developing native Dutch children; and (4) normally developing non
      native children. The interrelations between literacy subskills were also compared
      for native vs. non-native children with ID. RESULTS: The native and non-native
      students diagnosed as intellectually disabled produced substantially lower
      literacy scores than their non-disabled peers. The differences between the native
      (L1) and non-native (L2) children in regular vs. special education were found to
      depend on the aspect of literacy considered. Word decoding and language skills
      turned out to significantly predict the children's reading comprehension,
      although some differences in the strength of relationships could also be
      evidenced. CONCLUSIONS: The literacy achievement of intellectually disabled
      children with differing linguistic backgrounds generally falls behind that of
      their non-disabled peers. For word decoding, the non-native children in regular
      and special education were generally able to keep up with their native peers. For
      higher-order literacy abilities closely related to the mental lexicon, sentence
      processing and text processing, however, significant differences in the
      performances of the native (L1) and non-native (L2) children in regular vs.
      special education were found, suggesting a double disadvantage for the non-native
      children in special education.

PMID- 16961703
TI  - Assessing the effects of stimulation versus microswitch-based programmes on
      indices of happiness of students with multiple disabilities.
AB  - BACKGROUND: Stimulation and microswitch-based programmes are considered main
      strategies to promote indices of happiness in students with multiple
      disabilities. However, only limited attempts have been made to assess the
      relative effects of the two programmes. This study conducted such an assessment
      with seven students with multiple disabilities. METHODS: The first four phases of
      the study served to: (1) provide the students with a systematic exposure to each
      of the programmes; and (2) measure the programmes' effects on indices of
      happiness by comparing them with baseline levels. The fifth phase served to
      compare the programmes with each other. RESULTS: The first four phases of the
      study showed that the microswitch-based programme produced a significant increase
      in indices of happiness for all seven students, and the stimulation programme
      produced a significant increase for six students. During the fifth phase of the
      study (i.e. when the two programmes were alternated), the microswitch-based
      programme promoted significantly higher indices of happiness than the stimulation
      programme for four of the seven students. CONCLUSIONS: Microswitch-based
      programmes might be deemed preferable to stimulation programmes because they can
      promote higher or comparable indices of happiness while promoting the acquisition
      of adaptive responses and self-determination.

PMID- 16961704
TI  - Parenting stress of mothers and fathers of young children with cognitive delays
      in Vietnam.
AB  - BACKGROUND: This research examined the effects of child and family variables on
      stress experienced by mothers and fathers of young children with cognitive delays
      in Vietnam. METHODS: The mothers (n = 106) and fathers (n = 93) whose children
      (age range = 3-6 years) were identified as having cognitive delays participated
      in the interview survey. The survey consisted of a set of the standardized
      questionnaires that were translated into Vietnamese and assessed for the content
      validity in the Vietnamese context. RESULTS: Mothers experienced more stress than
      fathers. Path analyses were conducted for mothers and fathers separately. Mothers
      with female children, those with children of lower intellectual functioning, and
      those whose husbands had health conditions experienced more stress than the other
      mothers. Fathers with lower economic status and a smaller social support network
      were more stressed than the other fathers. Both mothers and fathers were more
      stressed when they experienced stronger stigma, although the effects were not
      significant when other variables were considered together in path analyses.
      CONCLUSIONS: The findings revealed traditional gender roles. Mothers were more
      affected by the child's characteristics and the spouse's functioning; they
      anticipated future problems related to the child's functioning more than fathers
      did. Fathers were more affected by concerns about the family's connection to the
      wider world such as economic issues and the social support network. Longitudinal
      studies of how social support and stigma affect families would be valuable.

PMID- 16961705
TI  - Vitamin D and fractures in people with intellectual disability.
AB  - BACKGROUND: People with intellectual disability (ID) are thought to be at an
      increased risk of fractures. The extent of this increase in risk has been
      incompletely documented in the literature, and the underlying reasons remain to
      be elucidated. METHODS: The aims of our study were to document the vitamin D
      status and fracture incidence in an intellectually disabled population, to test
      for associations between vitamin D status and possible risk factors for reduced
      vitamin D levels, and to determine the efficacy of oral vitamin D supplementation
      in restoring appropriate vitamin D levels in those found to be vitamin D
      insufficient. A 5-year retrospective audit of fractures in 337 individuals with
      ID receiving health care at a residential facility was performed. Data analysed
      included age, gender, mobility, dietary status, incident fractures, medications
      and 25-hydroxyvitamin D levels. Vitamin D insufficient individuals received oral
      vitamin D supplementation, and had repeat testing to assess treatment efficacy.
      RESULTS: In total, 57% of individuals tested were found to be vitamin D
      insufficient. Vitamin D insufficiency was strongly correlated with reduced
      mobility (P < 0.001) and difficulty with consuming solids (P < 0.001). However,
      the correlation between vitamin D levels and fractures was not significant (P =
      0.3). Oral vitamin D supplementation using cholecalciferol (vitamin D3) 100,000
      IU every 4 months was effective in correcting vitamin D insufficiency. Sixty
      eight fractures occurred over the study period in 52 individuals, a rate of 1
      fracture every 23.8 person years. A total of 55% of these fractures involved the
      extremities. Fractures were more common in men than in women. Peripheral
      fractures (hand, foot, wrist, ankle) accounted for 54% of all fractures, and were
      particularly prevalent in the most mobile individuals. CONCLUSIONS: Fractures and
      vitamin D insufficiency are relatively common in people with ID. This study did
      not find a significant association between vitamin D insufficiency and fractures
      in the study population. Oral vitamin D supplementation is effective in restoring
      normal vitamin D levels, and should be considered routinely for those at the
      highest risk.

PMID- 16961706
TI  - Dementia and mortality in persons with Down's syndrome.
AB  - BACKGROUND: Numerous studies have documented that persons with Down's syndrome
      (DS) are at an increased risk of Alzheimer's disease (AD). However, at present it
      is still not clear whether or not all persons with DS will develop dementia as
      they reach old age. METHODS: We studied 506 people with DS, aged 45 years and
      above. A standardized assessment of cognitive, functional and physical status was
      repeated annually. If deterioration occurred, the patients were examined and the
      differential diagnosis of dementia was made according to the revised Dutch
      consensus protocol and according to the ICD-10 Symptom Checklist for Mental
      Disorders. We compared our findings with those reported in the literature.
      RESULTS: The overall prevalence of dementia was 16.8%. Up to the age of 60, the
      prevalence of dementia doubled with each 5-year interval. Up to the age of 49,
      the prevalence is 8.9%, from 50 to 54, it is 17.7%, and from 55 to 59, it is
      32.1%. In the age category of 60 and above, there is a small decrease in
      prevalence of dementia to 25.6%. The lack of increase after the age of 60 may be
      explained by the increased mortality among elderly demented DS patients (44.4%)
      in comparison with non-demented patients (10.7%) who we observed during a 3.3
      year follow-up. There was no decrease in incidence of dementia in the age group
      of 60 and above. Our findings are very similar to those published in the
      literature. Patients with dementia were more frequently treated with
      antiepileptic, antipsychotic and antidepressant drugs. The history of depression
      was strongly associated with dementia. CONCLUSIONS: Our study is one of the
      largest population-based studies to date. We found that despite the exponential
      increase in prevalence with age, the prevalence of dementia in the oldest persons
      with DS was not higher than 25.6%.

PMID- 16961709
TI  - Role of interleukin-17F in chronic inflammatory and allergic lung disease.
AB  - IL-17 family members belong to a distinct category of cytokines that coordinate
      local tissue inflammation by inducing the release of pro-inflammatory and
      neutrophil-mobilizing cytokines. The importance of the IL-17 family in
      inflammatory and autoimmune disease is becoming increasingly apparent. IL-17F is
      a recently discovered member of the IL-17 family that has a number of biological
      activities through induction of various cytokines, chemokines, and mediators. IL
      17A, the founding member of the IL-17 family, and IL-17F are produced by several
      inflammatory cells, including activated T cells, in response to infectious and
      antigenic stimuli. Overexpression of IL-17A or IL-17F in the lungs results in
      induction of CXC chemokines and neutrophil recruitment. In a case-control study
      of 1125 unrelated Japanese subjects, a His161 to Arg161 (H161R) substitution in
      the third exon of the IL17F gene was shown to be associated with asthma and
      chronic obstructive pulmonary disease (COPD). Functionally, this variant failed
      to induce cytokines and chemokines, and interestingly, was able to antagonize the
      activity of wild-type IL-17F. These results provide an experimental basis for the
      observed genetic association with chronic inflammatory lung diseases, and also
      suggest the potential therapeutic utility of this antagonistic variant of IL-17F.
      Given that asthma and COPD are complex diseases involving a number of genetic and
      environmental factors, the genetic impact of IL-17F H161R with regard to the
      development of chronic airway inflammation likely varies among individuals with
      different genetic backgrounds and environmental exposures.

PMID- 16961710
TI  - Killed Mycobacterium vaccae suspension in children with moderate-to-severe atopic
      dermatitis: a randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: The hygiene hypothesis is often proposed to explain the high
      prevalence of atopy in the western world. Dysregulation of the immune system may
      result from inadequate exposure to micro-organisms such as mycobacteria. A small
      trial suggested that a killed extract of Mycobacterium vaccae ameliorates atopic
      dermatitis (AD). OBJECTIVES: To confirm in a large clinical trial whether killed
      M. vaccae ameliorates AD in 5-16-year-old children. METHODS: This was a
      randomized, placebo-controlled, double-blind, multi-centre study of the effect of
      intradermal injection of killed M. vaccae (0.1 or 1 mg) on patients, aged 5-16,
      with moderate-to-severe AD. Patients were followed up for 24 weeks. The primary
      end point was the change in severity of AD at 12 weeks, assessed using the six
      area, six-sign, atopic dermatitis (SASSAD) score. Secondary end points included
      changes in disease extent, patient's global assessment and children's dermatology
      life quality index. RESULTS: There were 166 patients randomized. The mean SASSAD
      score fell to a similar degree at week 12 in all treatment arms: from 33 to 24,
      (26%) in the high-dose group, from 30 to 23 (25%) in the low-dose group and from
      36 to 27 (24%) in the placebo group (P>0.05). Secondary end points followed the
      same trend. Adverse events were generally those expected to occur in this
      population. Injection site reactions occurred in 32 patients at week 4.
      CONCLUSIONS: M. vaccae was no more effective than the placebo in ameliorating the
      severity of AD.

PMID- 16961711
TI  - Contact with livestock--a protective effect against allergies and asthma?
AB  - BACKGROUND: A 'protective farm factor' possibly related to livestock exposure is
      hypothesized to reduce the risk for allergic sensitization. OBJECTIVE: The
      purpose of this study was to determine whether 4-H club youth, who have
      opportunities for contact with livestock through club activities, have reduced
      risks of respiratory and allergic symptoms according to residence on a farm or
      exposure to livestock. METHODS: A cross-sectional postal survey was completed by
      British Columbia 4-H members 8-20 years of age; a subset underwent skin prick
      testing as well. The association of farm residence and livestock exposure
      variables with symptoms were evaluated using logistic regression with adjustment
      for age, sex, cat and/or dog ownership, parental history of allergic disease,
      parental education, number of older siblings and exposure to smokers at home.
      RESULTS: Questionnaires were completed by 1158 participants (response rate
      50.3%); of these, a subset of 317 had skin prick tests (SPTs) (response rate
      64.4%). Current residence on a farm was associated with a lower prevalence of
      ever having wheeze and asthma, as well as symptoms of atopic dermatitis.
      Variables relating to residence in a farm or rural area with livestock were more
      strongly associated with respiratory and allergic symptoms than were the
      livestock exposure variables such as frequency of contact and hours of barn use.
      The adjusted odds ratios for living in a farm residence in comparison with a
      rural non-livestock area were 0.49 (95% confidence interval (CI) 0.27-0.89) for
      diagnosed asthma, 0.51 (95% CI 0.30-0.85) for allergic rhinitis and 0.45 (95% CI
      0.24-0.84) for atopic dermatitis. CONCLUSION: Our findings suggest that some
      aspects of the farm environment, not just attributable to contact with livestock,
      were protective for respiratory and allergic conditions among 4-H youth.

PMID- 16961712
TI  - Most of diaplacentally transferred allergen is retained in the placenta.
AB  - BACKGROUND: Transplacental transfer of nutritive and inhalant allergens has been
      described being potentially responsible for a series of events leading to antigen
      specific immune responses in the fetus. As such, cord blood T cell responses
      appear ubiquitously. However, studies failed to reveal a consistent dose-response
      relationship between antenatal allergen exposure and allergen-specific cellular
      reactivity in cord blood. OBJECTIVE: To examine the transfer process of allergens
      (ovalbumin (OVA), beta-lactoglobulin (BLG), birch pollen allergen Bet v1) in
      placental tissue (BeWo cell line, ex vivo placenta model). METHODS: The
      choriocarcinoma cell line BeWo was used to study the allergen uptake and transfer
      experiments in vitro. In the ex vivo placenta model the contribution of different
      placental compartments was evaluated. For this, immuno-histochemistry, immuno
      electronmicroscopy and ELISA techniques were applied using monoclonal antibodies
      to Bet v1, OVA and -BLG. RESULTS: In vitro transfer studies on a BeWo cell-layer
      revealed an intracellular allergen uptake and a trans-trophoblastic allergen
      transfer, which was temperature- and concentration dependent, pH sensitive and
      asymmetric. Allergen-specific staining of placental tissue after allergen
      perfusion (BLG) demonstrated bulk of the allergen in the syncytio-trophoblastic
      cell layer and minor staining in the villous stroma and in the endothelium of
      fetal vessels. Immunogold staining revealed an accumulation of the perfused
      allergen in the trophoblastic basement membrane. CONCLUSION: In vitro/ex vivo
      trans-trophoblastic and trans-placental allergen transfer is shown with an
      accumulation of most of the allergen in placental tissues, potentially explaining
      the missing direct dose-response relationship between prenatal (maternal)
      allergen exposure and allergen-specific cellular reactivity in cord blood.

PMID- 16961713
TI  - Association between air pollution and asthma admission among children in Hong
      Kong.
AB  - OBJECTIVE: To examine the association of air pollutants with hospital admission
      for childhood asthma in Hong Kong. METHODS: Data on hospital admissions for
      asthma, influenza and total hospital admissions in children aged < or =18 years
      at all Hospital Authority hospitals during 1997-2002 were obtained. Data on daily
      mean concentrations of particles with aerodynamic diameter <10 microm (i. e.
      PM10) and <2.5 microm (i. e. PM2.5), nitrogen dioxide (NO2), sulphur dioxide
      (SO2), and ozone (O3) and data on meteorological variables were associated with
      asthma hospital admissions using Poisson's regression with generalized additive
      models for correction of yearly trend, temperature, humidity, day-of-week effect,
      holiday, influenza admissions and total hospital admission. The possibility of a
      lag effect of each pollutant and the interaction of different pollutants were
      also examined. RESULTS: The association between asthma admission with change of
      NO2, PM10, PM2.5 and O3 levels remained significant after adjustment for multi
      pollutants effect and confounding variables, with increase in asthma admission
      rate of 5.64% (3.21-8.14) at lag 3 for NO2, 3.67% (1.52-5.86) at lag 4 for PM10,
      3.24% (0.93-5.60) at lag 4 for PM2.5 and 2.63% (0.64-4.67) at lag 2 for O3.
      Effect of SO2 was lost after adjustment. CONCLUSION: Ambient levels of PM10,
      PM2.5) NO2 and O3 are associated with childhood asthma hospital admission in Hong
      Kong.

PMID- 16961714
TI  - Association of interferon-gamma and interferon regulatory factor 1 polymorphisms
      with asthma in a family-based association study in Taiwan.
AB  - BACKGROUND: Asthma is a multi-factorial disorder caused by complex interactions
      between genetic and environmental factors. IFN-gamma and IFN regulatory factor 1
      (IRF-1) affect Th1/Th2 cytokine balance, and influence the differentiation of Th2
      cells, which influence the development of asthma. OBJECTIVE: This study
      investigated CA repeats polymorphism of the IFN-gamma gene and GT repeats
      polymorphism of the IRF-1 gene, which may predispose individuals to asthma
      pathogenesis. METHODS: In the present study, we used the
      transmission/disequilibrium test (TDT) to investigate the relationship between
      asthma and the IFN-gamma and IRF-1 polymorphisms by studying 348 subjects
      composed of 232 parents and 116 asthmatic children. RESULTS: For global TDT test,
      IFN-gamma CA repeats and IRF-1 GT repeat polymorphisms showed a significant
      association with asthma in children (P=0.009 and 0.017, respectively). We
      demonstrated that 13 CA repeats (138 bp) of IFN-gamma gene and 11 GT repeats (306
      bp) of IRF-1 gene are significantly preferentially transmitted to asthmatic
      children (T/NT=89/61, chi2=8.43, P<0.005 and T/NT=75/49, chi2=8.18, P<0.005,
      respectively). The offspring will have an increased risk of asthma when their
      parents transmit IFN-gamma 13 CA repeats (OR=1.83, P=0.009) and IRF1 11 GT
      repeats (OR=1.88, P=0.007) to them. But we observed that the IFN-gamma and IRF-1
      polymorphisms are not associated with IgE concentrations. CONCLUSION: These
      findings provide strong evidence of which IFN-gamma CA repeat and IRF-1 GT repeat
      polymorphisms influence the risk of asthma for children in Taiwan.

PMID- 16961715
TI  - Relationship between neurokinin 2 receptor gene polymorphisms and serum vascular
      endothelial growth factor levels in patients with toluene diisocyanate-induced
      asthma.
AB  - BACKGROUND: Among the various pathogenic mechanisms of toluene diisocyanate (TDI)
      induced asthma, a contribution from neurogenic inflammation has been suggested.
      OBJECTIVE: To evaluate neurokinin 2 receptor (NK2R) gene polymorphisms in
      association with the clinical phenotype of TDI-induced asthma, 70 TDI-induced
      occupational asthma (TDI-OA)patients, 59 asymptomatic exposed controls (AEC), and
      93 unexposed healthy controls (NC) were enrolled in the study. METHODS: Two
      single-nucleotide polymorphisms (SNPs) of NK2R, 7853G>A (Gly231Glu) and 11 424G>A
      (Arg375His), were genotyped using a single base extension method. The levels of
      PC20 methacholine, specific IgE and IgG to TDI-human serum albumin conjugate, and
      serum vascular endothelial growth factor (VEGF), matrix metalloproteinase-9, and
      TGF-beta1 were compared according to the NK2R genotypes of the subjects with TDI
      OA and AEC. RESULTS: No significant differences in allele, genotype, or haplotype
      frequencies of these two SNPs were noted among the three groups (P>0.05,
      respectively). Moreover, subjects with the NK2R 7853GG genotype had higher serum
      VEGF levels than those with GA or AA among the TDI-exposed workers (P=0.040).
      CONCLUSION: The NK2R 7853GG genotype may contribute to increased serum VEGF
      levels, which result in airway inflammation after TDI exposure.

PMID- 16961716
TI  - Levocetirizine in persistent allergic rhinitis and asthma: effects on symptoms,
      quality of life and inflammatory parameters.
AB  - Background Levocetirizine (LCZ) has been shown to be effective in allergic
      rhinitis. We evaluated its clinical efficacy, antinflammatory actions and its
      effects on quality of life (QoL) with a specific instrument in the asthma
      rhinitis comorbidity. Methods Fifty adult patients with persistent rhinitis
      with/without asthma were enrolled. After a 1-week run-in for baseline evaluation,
      they were randomized to LCZ or placebo for 8 weeks. Cromolyn and salbutamol were
      permitted on demand. Rhinoconjunctivitis and asthma symptoms were evaluated by
      diary cards. QoL was assessed by the specific Rhinasthma questionnaire and the
      generic SF-36 at different time-points. Nasal scrapings and lavages were also
      performed for inflammatory cell count and mediator assessment. Results Ten
      patients dropped out for unrelated reasons and the remaining completed the study
      with no side-effect. Symptoms began to decrease in the active group at the second
      week of treatment when the difference with the placebo group became significant
      (0.05) and so remained until the end of the trial. Starting from 2 weeks of
      therapy, there was a significant decrease vs. baseline in all the four components
      of the Rhinasthma questionnaire only in the active group. The intergroup
      comparison became significant (P<0.05) at 4 weeks. The SF-36 detected only
      sporadic differences between groups. Eosinophils and neutrophils in nasal
      scraping were significantly decreased in the LCZ group vs. baseline at all times.
      Nasal mediators were under the detection limits and no analysis could be
      performed. In the active group, only two patients used rescue medications
      compared with 13 patients in the placebo group. Conclusions LCZ is clinically
      effective and capable of improving the rhinitis-asthma-related QoL.

PMID- 16961717
TI  - Airborne exposure to wheat allergens: measurement by human immunoglobulin G4 and
      rabbit immunoglobulin G immunoassays.
AB  - BACKGROUND: Exposure to airborne wheat allergens in the bakery trade is
      associated with a high risk of occupational allergy and asthma. Control and
      reduction of allergen exposure require relatively simple but reliable monitoring
      techniques. We developed new rabbit IgG-based enzyme immunoassays (EIA) for wheat
      allergens, which might be a convenient alternative for the thus far used human
      IgG4 inhibition assay. METHODS: The reactivity and specificity of rabbit
      antibodies were assessed by EIA and immunoblotting, and compared with those of
      IgE from wheat-sensitized bakers, and with the antibodies used in the IgG4
      inhibition EIA. An IgG inhibition and a sandwich EIA were developed for analysis
      of airborne dust samples. RESULTS: Human IgG4 and rabbit IgG inhibition EIAs had
      comparable sensitivities, with limits of detection (LOD) between 18 and 88 ng/mL,
      while the sandwich EIA was much more sensitive (LOD<0.2 ng/mL). Human IgG4 and
      rabbit IgG reacted in immunoblotting with most of the IgE-binding wheat proteins,
      although with quantitative differences. All three assays showed a strong reaction
      with wheat proteins, and some cross-reactivity with rye and barley, but were
      further highly specific for cereal flour proteins. Concentrations measured with
      the three EIAs in 432 airborne dust samples were highly correlated (r>0.95) and
      their absolute values showed less than 10-20% differences. CONCLUSION: The rabbit
      IgG EIAs are valid substitutes for the human IgG4 inhibition EIA, with important
      practical advantages. The inhibition EIA is recommended for routine wheat
      allergen measurements. The sandwich EIA may be used to measure low allergen
      levels, as in short task-related exposure measurements or in subfractions of
      airborne dust samples.

PMID- 16961718
TI  - An amplified sandwich EIA for the measurement of soy aeroallergens.
AB  - BACKGROUND: Soy hull low-molecular-weight (SHLMW) allergens were responsible for
      the soy asthma epidemics in Barcelona, with one 7.5 kDa protein (Gly m 1) being
      the main IgE-binding component. The aims of this study were to develop a
      sensitive sandwich enzyme immunoassay (EIA) using rabbit polyclonal antibodies to
      measure low levels of SHLMW allergens, and to compare this method with the
      previously described human IgE EIA-inhibition technique. METHODS: IgG was
      isolated from serum of rabbits immunized with a chromatographically purified
      SHLMW extract (SHLMWE). Antibody-binding profiles were compared with those of
      human IgE anti-soy protein antibodies by Western blot analysis. An amplified
      sandwich EIA was developed using the purified SHLMWE as a calibration standard.
      Results were expressed in nanograms per millilitre. To compare the two assays, 54
      air samples were analysed by both methods. RESULTS: SDS-PAGE of the SHLMWE
      revealed four bands of 6, 8, 15 and 17 kDa. Gly m 1 in the SHLMWE was identified
      by fingerprinting. The detection limit of the assay was 40 pg/mL. The two methods
      correlated well (r=0.89; P<0.001). The allergen concentration was detected in all
      54 (100%) samples by the sandwich EIA but in only 37 (68.5%) by the EIA
      inhibition. CONCLUSIONS: The amplified sandwich EIA for SHLMW components has a
      high sensitivity and appeared to be a useful tool for the measurement of airborne
      SHLMW allergens, even at relatively low concentrations. Moreover, the method uses
      rabbit antibodies at high dilutions and does not require human sera, with limited
      availability and quantitative and qualitative pool-to-pool variability.

PMID- 16961719
TI  - Increased expression of collagen receptors: alpha1beta1 and alpha2beta1 integrins
      on blood eosinophils in bronchial asthma.
AB  - BACKGROUND: Eosinophils are one of the major effector cells in bronchial asthma.
      Their infiltration of airways correlates with the asthma severity. Recruitment
      and activation of eosinophils are partially mediated by integrins alpha4beta1 and
      alpha4beta7. Collagens type I and IV constitute important components of
      extracellular matrix and vascular basement membrane, respectively. Therefore,
      collagen-binding integrins (alpha1beta1 and alpha2beta1) may also play a role in
      eosinophil lung infiltration. OBJECTIVE: To evaluate the possible presence of
      alpha1beta1 and alpha2beta1 integrins on peripheral blood eosinophils from
      asthmatic subjects. METHODS: Collagen receptors were studied on eosinophils
      separated by immunomagnetic CD16-negative method from healthy donors (n=13) and
      patients with moderate persistent atopic bronchial asthma (n=15). Surface
      receptor identification was performed by flow cytometry and cell adhesion assay.
      RESULTS: Eosinophils isolated from the patients showed increased expression of
      both alpha1beta1 and alpha2beta1 integrins as compared with healthy controls.
      Moreover, adhesive function of eosinophils to collagen type IV was inhibited by
      snake venom disintegrins: viperistatin and obtustatin. These disintegrins contain
      KTS active motif and are specific inhibitors of alpha1beta1 integrin. CONCLUSION:
      We demonstrated for the first time that collagen receptors: alpha1beta1 and
      alpha2beta1 integrins are overexpressed on the surface of peripheral blood
      eosinophils of asthmatic subjects. Further studies may reveal potential
      application of KTS-disintegrins or their structural analogs for therapy of
      bronchial asthma.

PMID- 16961722
TI  - Oxidative stress as the leading cause of acute myocardial infarction in
      diabetics.
AB  - The risk factors, such as hypertension and metabolic syndrome, tend to promote
      heart pathology. These risk factors can aggravate concomitant heart insults as
      well. Diabetes mellitus represents one of the most important risk factors for the
      development of heart pathology. By itself it represents a source of vascular and
      heart dysfunction through formation of reactive oxygen species (ROS) and can
      compromise the recovery from cardiovascular diseases. This review focuses on the
      evidence that cellular oxidative stress is the leading cause of the worst outcome
      of myocardial infarction (MI) in diabetics. Hyperglycemia is viewed in this
      article as the primary mediator of a cascade of heart damaging events, starting
      from ROS formation and leading to myocardial ischemia, inflammation and death of
      myocytes. This article also provides insights into why diverse therapeutic
      interventions, which have in common the ability to reduce oxidative stress and
      inflammation, can impede or delay the onset of complications of myocardial
      infarction in diabetic patients.

PMID- 16961720
TI  - Airway hyper-responsiveness in allergic asthma in guinea-pigs is mediated by
      nerve growth factor via the induction of substance P: a potential role for trkA.
AB  - BACKGROUND: The neurotrophin nerve growth factor (NGF) has been implicated as a
      mediator in allergic asthma. Direct evidence that inhibition of NGF-induced
      activation of neurotrophin receptors leads to improvement of airway symptoms is
      lacking. We therefore studied the effects of inhibitors of NGF signal
      transduction on the development of airway hyper-responsiveness (AHR) and
      pulmonary inflammation in a guinea-pig model for allergic asthma. METHODS: Airway
      responsiveness to the contractile agonist histamine was measured in vivo in
      guinea-pigs that were sensitized and challenged with ovalbumin (OVA).
      Inflammatory cell influx and NGF levels were determined in bronchoalveolar lavage
      fluid (BALF). Substance P, a key mediator of inflammation, was measured in lung
      tissue by radioimmunoassay, while substance P immunoreactive neurons in nodose
      ganglia were measured by immunohistochemistry. RESULTS: OVA challenge induced an
      AHR after 24 h in OVA-sensitized guinea-pigs. This coincided with an increase in
      the amount of NGF in BALF. Simultaneously, an increase in the percentage of
      substance P immunoreactive neurons in the nodose ganglia and an increase in the
      amount of substance P in lung tissue were found. We used tyrosine kinase
      inhibitors to block the signal transduction of the high-affinity NGF receptor,
      tyrosine kinase A (trkA). Treatment with the tyrosine kinase inhibitors (K252a or
      tyrphostin AG879) both inhibited the development of AHR, and prevented the
      increase in substance P in the nodose ganglia and lung tissue completely whereas
      both inhibitors had no effect on baseline airway resistance. Neither treatment
      with K252a or tyrphostin AG879 changed the influx of inflammatory cells in the
      BALF due to allergen challenge. CONCLUSIONS: We conclude that substance P plays a
      role in the induction of AHR in our model for allergic asthma which is most
      likely mediated by NGF. As both tyrosine kinase inhibitors AG879 and K252a show a
      similar inhibitory effect on airway function after allergen challenge, although
      both tyrosine kinase inhibitors exhibit different non-specific inhibitory effects
      on targets other than trkA tyrosine kinases, it is likely that the induction of
      substance P derived from sensory nerves is mediated by NGF via its high-affinity
      receptor trkA.

PMID- 16961723
TI  - DY-9760e, a novel calmodulin inhibitor, exhibits cardioprotective effects in the
      ischemic heart.
AB  - DY-9760e (3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1
      (4-imidazolylmethyl)-1H-indazole dihydrochloride-3.5 hydrate) inhibits Ca(2+)/CaM
      dependent nitric oxide synthase (NOS), thereby inhibiting nitric oxide (NO)
      production. In cardiomyocytes from ischemic rat heart NO and superoxide levels
      are increased causing protein tyrosine nitration. In hearts subjected to
      ischemia/reperfusion DY-9760e totally abolishes protein tyrosine nitration.
      Notably, DY-9760e also inhibits calpain and cas-pase-3 activation that occurs
      prior to apoptosis in cardiomyocytes. In ischemic hearts fodrin is the substrate
      for calpain. DY-9760e inhibits fodrin breakdown in the peri-infarct area rather
      than in the infarct core. In the ischemic rat brain DY-9760e inhibits caspase-3
      induced proteolysis of calpastatin, an endogenous calpain inhibitor, suggesting
      that crosstalk between calpain and caspase-3 is mediated by calpastatin
      breakdown. Thus, DY-9760e rescues neurons and cardiomyocytes from ischemic injury
      by inhibiting crosstalk between calpain and caspase-3 as well as protein tyrosine
      nitration.

PMID- 16961724
TI  - CPU86017: a novel Class III antiarrhythmic agent with multiple actions at ion
      channels.
AB  - CPU86017 is a novel Class III antiarrhythmic agent derived from berberine and
      with an improved pharmacological profile, solubility and bioavailability. It is
      active in suppressing arrhythmias in several animal models. The ED(50) of
      CPU86017 for suppressing ischemia/reperfusion arrhythmias in rats was 0.22 mg/kg
      against 2.23 mg/kg for lidocaine. CPU86017 is about 10-fold more potent than
      lidocaine. It blocks I(K(R.tail)), I(K(S)), and I(Ca(L)) currents with IC(50)
      values of 25, 14.4, and 11.5 microM, respectively. The plasma t(1/2) of CPU86017,
      i.v. bolus, in rabbits and dogs is approximately 90 min. The effective plasma
      levels of CPU86017 in rabbits required to delay the appearance of oubain-induced
      ventricular arrhythmias is in the range of 0.13-0.31 microg/mL. Higher levels of
      the drug are required to eliminate ventricular arrhythmias produced by two-stage
      ligation of the coronary artery in anesthetized dogs. Drug levels in myocardium
      are much higher than in plasma. CPU80617 has an antioxidant effect that is likely
      to contribute to its antiarrhythmic activity. The abnormal expression of the
      ryanodine receptor type 2 (RyR2) and of FKBP12.6 is reduced by CPU80617 during
      its ventricular tachyarrhythmia-suppressing action. CPU86017 appears to be a
      promising antiarrhythmic agent with a cardioprotective action. It can be expected
      to protect from malignant arrhythmias and sudden cardiac death by suppressing
      molecular events caused by channelopathies.

PMID- 16961725
TI  - Role of adenosine as adjunctive therapy in acute myocardial infarction.
AB  - Although early reperfusion and maintained patency is the mainstay therapy for ST
      elevation myocardial infarction, experimental studies demonstrate that
      reperfusion per se induces deleterious effects on viable ischemic cells. Thus
      "myocardial reperfusion injury" may compromise the full potential of reperfusion
      therapy and may account for unfavorable outcomes in high-risk patients. Although
      the mechanisms of reperfusion injury are complex and multifactorial, neutrophil
      mediated microvascular injury resulting in a progressive decrease in blood flow
      ("no-reflow" phenomenon) likely plays an important role. Adenosine is an
      endogenous nucleoside found in large quantities in myocardial and endothelial
      cells. It activates four well-characterized receptors producing various
      physiological effects that attenuate many of the proposed mechanisms of
      reperfusion injury. The cardio-protective effects of adenosine are supported by
      its role as a mediator of pre- and post-conditioning. In experimental models,
      administration of adenosine in the peri-reperfusion period results in a marked
      reduction in infarct size and improvement in ventricular function. The
      cardioprotective effects in the canine model have a narrow time window with the
      drug losing its effect following three hours of ischemia. Several small clinical
      studies have demonstrated that administration of adenosine with reperfusion
      therapy reduces infarct size and improves ventricular function. In the larger
      AMISTAD and AMISTAD II trials a 3-h infusion of adenosine as an adjunct to
      reperfusion resulted in a striking reduction in infarct size (55-65%). Post hoc
      analysis of AMISTAD II showed that this was associated with significantly
      improved early and late mortality in patients treated within 3.17 h of symptoms.
      An intravenous infusion of adenosine for 3 h should be considered as adjunctive
      therapy in high risk-patients undergoing reperfusion therapy.

PMID- 16961726
TI  - Pharmacologic profile and therapeutic potential of NCX 4016, a nitric oxide
      releasing aspirin, for cardiovascular disorders.
AB  - NCX 4016, 2-(acetyloxy)benzoic acid 3-[(nitrooxy)methyl]phenyl ester, is a new
      molecule in which a nitric oxide (NO)-releasing moiety is covalently linked to
      aspirin. After enzymatic metabolism, NCX 4016 releases both components. In vitro
      and in some animal models, these components exert their pharmacologic effects
      simultaneously. Nitric oxide (NO) is a small gaseous molecule that exerts several
      activities which may prevent atherothrombotic disorders. Moreover, it displays a
      protective activity on the gastric mucosa. NCX 4016 has been shown to inhibit
      platelet activation in vitro more effectively than aspirin, to inhibit smooth
      muscle cell proliferation, to exert an endothelial cell protective activity and
      to suppress the function of several inflammatory cells potentially involved in
      atherothrombosis. In animal models, NCX 4016 protected from platelet
      thromboembolism, prevented restenosis in atherosclerosis-prone animals, protected
      the heart from ischemia/reperfusion injury, and induced neoangiogenesis in
      critically ischemic limbs. Moreover, it displayed little or no gastric toxicity
      and appeared to protect stomach from noxious stimuli, including aspirin. NCX 4016
      has been evaluated in healthy volunteers and found to inhibit platelet cyclo
      oxygenase-1 (COX-1) similarly to or slightly less than aspirin, to raise the
      circulating levels of NO-degradation products, and to have little or no gastric
      toxicity in short term studies. In particular, in phase II studies, NCX 4016 had
      favorable effects on effort-induced endothelial dysfunction in intermittent
      claudication and on platelet-activation parameters elicited by short-term
      hyperglycemia in type II diabetics. In patients with type II diabetes the effects
      of NCX 4016 on microalbuminuria and on some hemodynamic parameters were
      promising. The pharmacokinetics of in vivo aspirin- and NO- released by NCX 4016,
      as well as the bioavailability of the two molecules, were not yet adequately
      studied. Also, the long-term tolerability of NCX 4016, as well as its possible
      effectiveness in preventing ischemic cardiovascular events and progression of
      atherosclerosis, should be explored.

PMID- 16961727
TI  - Cardiovascular therapeutic aspects of soluble epoxide hydrolase inhibitors.
AB  - Soluble epoxide hydrolase (sEH) is an enzyme responsible for the conversion of
      lipid epoxides to diols by the addition of water. Biological actions on the
      cardiovascular system that are attributed to epoxides include vasodilation,
      antiinflammatory actions and vascular smooth muscle cell antimigratory actions.
      Conversion of arachidonic acid epoxides to diols by sEH diminishes the beneficial
      cardiovascular properties of these epoxyeicosano-ids. Cardiovascular diseases in
      animal models and humans have been associated with decreased epoxygenase activity
      or increased sEH activity and these changes are responsible for the progression
      of the disease state. More recently, sEH gene polymorphisms in the human
      population have been associated with increased risk for cardiovascular diseases.
      Thus the biological actions of epoxyeicosanoids and the sEH enzyme are ideal
      therapeutic targets for cardiovascular diseases. The rapid development of 1,3
      disubstituted urea based sEH inhibitors over the past five years has resulted in
      a number of studies demonstrating cardiovascular protection. sEH inhibitors have
      antihypertensive and antiinflammatory actions and have been demonstrated to
      decrease cerebral ischemic and renal injury in rat models of hypertension. These
      findings of beneficial actions in animal models of disease position the sEH
      enzyme as a promising therapeutic target for cardiovascular diseases.

PMID- 16961728
TI  - Successful percutaneous coronary intervention using bivalirudin in a patient with
      chronic lymphocytic leukemia and thrombocytopenia.
AB  - A patient with chronic lymphocytic leukemia and thrombocytopenia who underwent
      percutaneous coronary intervention (PCI) and stenting is presented. Patients with
      these concomitant diseases who require invasive cardiac procedures are at
      increased risk for ischemic and bleeding complications and the choice of
      anticoagulation in these patients is critical. In the present case,
      anticoagulation was achieved with the direct thrombin inhibitor bivalirudin. No
      complications were reported, and the patient tolerated the procedure well. This
      case suggests that bivalirudin may be safely used in patients who are at an
      increased risk of bleeding undergoing PCI.

PMID- 16961729
TI  - Reply to Pich et al.: intrasinusoidal bone marrow infiltration and splenic
      marginal zone lymphoma: a quantitative study.

PMID- 16961731
TI  - The 5' stem-loop and its role in mRNA stability in maize S cytoplasmic male
      sterility.
AB  - The co-transcribed orf355-orf77 region of the mitochondrial genome is associated
      with S cytoplasmic male sterility (CMS-S) in maize; the amounts of its 1.6- and
      2.8-kb transcripts were previously shown to be greatly reduced in fertility
      restored microspores relative to the amounts in sterile plants. To investigate
      the mechanism underlying this reduction, detailed analysis of the 5' and 3'
      termini of these transcripts was conducted. Using 3' RACE analysis, the
      polyadenylation sites of the 1.6- and 2.8-kb transcripts were mapped adjacent to
      a 3' stem-loop, which may play an important role in stabilizing their 3' ends. No
      difference was found between the polyadenylation sites in sterile and fertility
      restored microspores that could account for the differences in orf355-orf77
      transcript levels. The 5' terminus of the 1.6-kb transcript was further studied
      by primer extension; the result revealed that there was a deletion of nine
      nucleotides only in fertility-restored microspores, and that this deletion
      eliminated a 5' stem-loop sequence. We propose that the elimination of the 5'
      stem-loop in the fertility-restored microspores could be the cause of the
      degradation of the 1.6-kb transcript. Because the 2.8-kb transcript can be
      cleaved to generate the 1.6-kb transcript, the amount of the 2.8-kb transcript is
      also reduced in fertility-restored microspores.

PMID- 16961732
TI  - Ethylene-induced stomatal closure in Arabidopsis occurs via AtrbohF-mediated
      hydrogen peroxide synthesis.
AB  - Ethylene is a plant hormone that regulates many aspects of growth and
      development. Despite the well-known association between ethylene and stress
      signalling, its effects on stomatal movements are largely unexplored. Here,
      genetic and physiological data are provided that position ethylene into the
      Arabidopsis guard cell signalling network, and demonstrate a functional link
      between ethylene and hydrogen peroxide (H(2)O(2)). In wild-type leaves, ethylene
      induces stomatal closure that is dependent on H(2)O(2) production in guard cells,
      generated by the nicotinamide adenine dinucleotide phosphate hydrogen (NADPH)
      oxidase AtrbohF. Ethylene-induced closure is inhibited by the ethylene
      antagonists 1-MCP and silver. The ethylene receptor mutants etr1-1 and etr1-3 are
      insensitive to ethylene in terms of stomatal closure and H(2)O(2) production.
      Stomata of the ethylene signalling ein2-1 and arr2 mutants do not close in
      response to either ethylene or H(2)O(2) but do generate H(2)O(2) following
      ethylene challenge. Thus, the data indicate that ethylene and H(2)O(2) signalling
      in guard cells are mediated by ETR1 via EIN2 and ARR2-dependent pathway(s), and
      identify AtrbohF as a key mediator of stomatal responses to ethylene.

PMID- 16961733
TI  - A role for caleosin in degradation of oil-body storage lipid during seed
      germination.
AB  - Caleosin is a Ca(2+)-binding oil-body surface protein. To assess its role in the
      degradation of oil-bodies, two independent insertion mutants lacking caleosin
      were studied. Both mutants demonstrated significant delay of breakdown of the
      20:1 storage lipid at 48 and 60 h of germination. Additionally, although
      germination rates for seeds were not affected by the mutations, mutant seedlings
      grew more slowly than wild type when measured at 48 h of germination, a defect
      that was corrected with continued growth for 72 and 96 h in the light. After 48 h
      of germination, wild-type central vacuoles had smooth contours and demonstrated
      internalization of oil bodies and of membrane containing alpha- and delta
      tonoplast intrinsic proteins (TIPs), markers for protein storage vacuoles. In
      contrast, mutant central vacuoles had distorted limiting membranes displaying
      domains with clumps of the two TIPs, and they contained fewer oil bodies. Thus,
      during germination caleosin plays a role in the degradation of storage lipid in
      oil bodies. Its role involves both the normal modification of storage vacuole
      membrane and the interaction of oil bodies with vacuoles. The results indicate
      that interaction of oil bodies with vacuoles is one mechanism that contributes to
      the degradation of storage lipid.

PMID- 16961734
TI  - Early infection of scutellum tissue with Agrobacterium allows high-speed
      transformation of rice.
AB  - Several approaches have recently been adopted to improve Agrobacterium-mediated
      transformation of rice, both to generate the large number of T-DNA insertion
      plants needed for functional analysis of the rice genome, and for production of
      rice with additional agronomical value. However, about 3 months of in vitro
      culture is still required for isolation of transgenic rice plants. Here, we
      report the competency of scutellum tissue from 1-day pre-cultured seeds for
      Agrobacterium-mediated transformation. Furthermore, early infection of rice seeds
      with Agrobacterium enhanced efficient selection of transformed calli. Using our
      system, we successfully regenerated transgenic rice plantlets within a month of
      the start of the aseptic culture of mature seeds. Our new system should reduce
      the somaclonal variation accompanying prolonged culture of rice cells in the
      dedifferentiated state and facilitate the molecular breeding of rice.

PMID- 16961736
TI  - Introduction: new approaches to the detection and management of inflammatory
      bowel disease: from genetic testing to treatment strategies.

PMID- 16961737
TI  - Review article: genetic susceptibility and application of genetic testing in
      clinical management of inflammatory bowel disease.
AB  - The volume of research undertaken on the genetic susceptibility of inflammatory
      bowel disease (IBD) has been tremendous, and over 10 chromosomal regions have
      been identified by genome-wide scanning. Fine-mapping approaches and candidate
      gene studies have already led to the identification of several susceptibility
      genes, including CARD15 (NOD2), DLG5, novel organic cation transporter (OCTN) 1
      and 2, and CARD4 (NOD1). The CARD15 gene is the most understood at present and
      explains around 20% of the genetic predisposition to Crohn's disease. Although
      the clinical implications of genetic testing are limited at present, genetic
      research has advanced our understanding of the clinical heterogeneity and the
      complex interactions between genetic and environmental risk factors in IBD. Genes
      also interfere with the metabolism of drugs and may influence the clinical
      response and drug-related toxicity. Ultimately, researchers and clinicians aim to
      personalize medicine based on a patient's genotype, although azathioprine
      (thiopurine methyltransferase polymorphisms) is the only drug to date where
      pharmacogenetics has shown clinical relevance in IBD. In the future, it is
      anticipated that genetic markers will be implemented in an integrated molecular
      diagnostic and prognostic approach to managing our patients.

PMID- 16961738
TI  - Review article: the role of bacteria in onset and perpetuation of inflammatory
      bowel disease.
AB  - We review the evidence that strongly suggests a role of the intestinal microbiota
      in the onset and perpetuation of inflammatory bowel disease (IBD). Experimental
      studies consisted of suppressing micro-organisms from the microbiota (using germ
      free or gnotoxenic animals or antibiotics), introducing new micro-organisms or
      microbial components (e.g. probiotics, CpG-DNA) or selectively increasing some
      endogenous bacteria (e.g. using prebiotics). Intervention studies were performed
      in patients or animal models of spontaneous or chemically-induced colitis.
      Information was also obtained from observational studies that described the
      composition of the faecal and mucosal microbiota at various stages of the disease
      process and in controls. Many have used culture-independent techniques that
      identify bacteria based on the nucleic acid sequence of ribosomal RNA molecules.
      Microbiota in patients with IBD seem to be characterized by high concentrations
      of bacteria in contact with the mucosa, instability, the presence of high numbers
      of unusual bacteria and sometimes a reduction in the biodiversity. Studies
      searching for a generalized or localized dysbiosis in IBD are discussed, as well
      as those trying to identify bacterial molecules and receptors, which may be
      implicated in triggering the inflammatory process.

PMID- 16961739
TI  - Review article: capsule endoscopy - are all small intestinal lesions Crohn's
      disease?
AB  - Capsule endoscopy is the gold-standard examination for the diagnosis of Crohn's
      disease (CD) of the small intestine. Its incremental yield over other imaging
      modalities is above 30%. It is important to keep in mind that over 10% of healthy
      subjects demonstrate mucosal breaks and erosions in their small intestinal
      mucosa. Thus, one should refrain from diagnosing CD based on the existence of a
      few erosions and ulcers of the small intestine. Such erosions and ulcers may in
      fact be the result of non-steroidal anti-inflammatory drug intake and other
      pathological conditions such as lymphoid hyperplasia, lymphoma and radiation
      enteritis. Non-steroidal anti-inflammatory drug intake should, therefore, be
      excluded as a cause prior to relating the presence of lesions to CD. Misdiagnosis
      of CD may be harmful to the patient because if unresponsive, intensification of
      therapy may occur and occasionally an unnecessary operation may be performed. At
      the same time, the patient may also be deprived of the appropriate therapy for
      the treatment of their condition.

PMID- 16961740
TI  - Review article: can post-operative recurrence in Crohn's disease be prevented?
AB  - The decision regarding prophylactic treatment after surgery in Crohn's disease
      (CD) requires a good estimation of the risk of recurrence. It is also important
      to consider the consequences of recurrence for the patient, and the risks and
      benefits of treatment, bearing in mind that it will be given over a long period.
      Several drugs have been tried to decrease the risk of recurrence. Corticosteroids
      and budesonide have proved to be ineffective. Mesalazine has significant efficacy
      in some, but not all trials, and a meta-analysis has established that it
      decreases the absolute risk by 10-15% after 1-2 years. Mercaptopurine seemed to
      be effective in a recent study. Metronidazole and ornidazole have significant
      efficacy, but cannot be tolerated for long periods. Probiotics represent a new
      approach, but evidence for their efficacy in CD is still lacking. In the past,
      the strategy was to give no treatment until clinical recurrence. Another approach
      is to give no treatment, and then to treat the patient according to severity of
      endoscopic recurrence. Alternative strategies include treating all patients with
      mesalazine until either severe endoscopic or clinical recurrence occurs, and then
      to use azathioprine/mercaptopurine, or to give azathioprine/mercaptopurine
      immediately, especially in high-risk patients.

PMID- 16961741
TI  - Review article: recurrence of Crohn's disease after surgery - the need for
      treatment of new lesions.
AB  - Crohn's recurrence is the appearance of objective signs - defined radiologically,
      endoscopically or pathologically - of Crohn's disease in the bowel of a patient
      who has previously had a resection of all macroscopically diseased tissue. New
      lesions can be visualized endoscopically within weeks to months after ileal
      resection and ileocolonic anastomosis in the neoterminal ileum. The evolution of
      these lesions mimics the natural history of ileal Crohn's disease at the onset.
      If we are able to prevent recurrence of early lesions, we will probably interrupt
      the natural course of the disease. The drugs tested to date include different 5
      aminosalicylate formulations, nitro-imidazole antibiotics, steroids and
      azathioprine. None of these therapies has convincingly been shown to prevent
      recurrent lesions. Metronidazole and ornidazole are effective, but cannot be used
      in the long-term because of side effects. Since there is a lag time of months to
      years between the development of recurrent lesions in the bowel and the
      recurrence of symptoms, we recommend performing imaging of the bowel 6 months
      after the operation to assess the severity of recurrence, and basing the further
      treatment strategy on this assessment.

PMID- 16961742
TI  - Review article: should we treat symptoms or lesions in Crohn's disease? The case
      for treating symptoms.
AB  - Apart from treating symptoms, mucosal healing is a reasonable aim of therapy in
      Crohn's disease. In most patients, however, the disease takes a mild course and
      treating symptoms seems sufficient. Eliminating lesions may change the course of
      the disease long-term but this has not yet been proven. Thus far we need to treat
      symptoms efficiently and may attempt to restore bacterial epithelial interaction.

PMID- 16961743
TI  - Review article: high-dose aminosalicylates to induce and maintain remissions in
      ulcerative colitis.
AB  - Sulfasalazine was the first aminosalicylate to be used for induction and
      maintenance therapy of ulcerative colitis (UC). Initial trials demonstrated a
      dose response that was compromised by dose-related intolerance. Recognition that
      the 5-aminosalicylic acid moiety (5-ASA, mesalazine) is the active ingredient of
      sulfasalazine has allowed the development of sulpha-free formulations of
      mesalazine and alternative azo-bond derivatives (olsalazine, balsalazide) that
      substantially reduce the dose-related (and allergic) consequences of the
      sulfapyridine moiety of sulfasalazine. Dose-ranging studies of mesalazine
      formulations for induction of remission have demonstrated increased efficacy of
      oral mesalazine up to 4-4.8 g/day, particularly in patients with more moderate
      disease activity. Combination therapy with oral and rectal mesalazine provide
      additional efficacy for patients with both distal and extensive colitis. The
      mesalazine formulations have dose-related benefits without dose-related side
      effects. In contrast, the azo-bond formulations are compromised by secretory
      diarrhoea at doses providing greater than 2-2.4 g/day of mesalazine. There are
      less data regarding dose-related benefits of aminosalicylates to maintain
      remissions in UC greater than 1.6 g/day of mesalazine, although the absence of
      dose-related side effects allows continuation of the same inductive dose through
      maintenance treatment without dose-related toxicity.

PMID- 16961744
TI  - Review article: aminosalicylates for distal colitis.
AB  - About two-thirds of patients with ulcerative colitis have an inflammatory
      involvement distal to the splenic flexure and therefore may be effectively
      treated with topical treatment. This allows the delivery of the active drug
      directly to the site of inflammation, limiting the systemic absorption and the
      potential side effects. Topical aminosalicylate therapy is the most effective
      approach, provided that the formulation reaches the upper extent of the disease.
      Suppositories should be considered the treatment of choice for proctitis and
      distal sigmoiditis. A 1 g Pentasa-suppository once daily induces a quicker
      clinical and endoscopic remission and was better tolerated than a 500-mg
      suppository twice daily. Enemas, foams and gel, thanks to their proximal spread,
      should be the treatment of choice for proctosigmoiditis and left-sided colitis.
      Oral aminosalicylates are less effective than topical therapies for patients with
      active disease; however, a combination of oral and topical aminosalicylates can
      be successfully tried in refractory patients. Topical aminosalicylates also play
      an important role in the maintenance of remission, and the combination of oral
      plus rectal 5-aminosalicylate is superior to the single agent. Patients who
      prefer not to continue on long-term rectal therapy can be treated with oral
      aminosalicylates.

PMID- 16961745
TI  - Review article: how to control and improve adherence to therapy in inflammatory
      bowel disease.
AB  - Any chronic disease is a risk situation for non-adherence to treatment. This
      results in suboptimal medication, and poor disease control. Adherence and
      compliance are directly related to therapeutic success, which is further
      complicated in inflammatory bowel disease patients. There is a wide array of
      circumstances that increase the likelihood of non-compliance in a given patient:
      difficult-to-follow treatment schedules (multiple doses and multiple drugs),
      insufficient patient information, longer evolution of the disease and inactive
      disease. Depression, male gender, active employment and living alone are also
      associated with poorer adherence to therapy. Monitoring drug intake is possible
      in many circumstances, directly or indirectly (urinary salicylate levels;
      erythrocyte metabolites and increased mean corpuscular volume and bilirubin in
      patients under azathioprine; blood levels of ciclosporin or tacrolimus). However,
      such measures are probably better utilized for dose adjustment and not for the
      identification of non-compliant patients. High-risk patients are a target group
      in which pre-emptive intervention could ensure better compliance. If the question
      of non-adherence arises, for instance, as a possible cause of therapy failure,
      the patient should be carefully approached. This should take into consideration
      factors that may be corrected and, most importantly, should aim at building a
      better patient-doctor relationship.

PMID- 16961746
TI  - Review article: what are the important endoscopic lesions for detection of
      dysplasia in inflammatory bowel disease?
AB  - It is recognized that inflammatory bowel diseases predispose to colorectal
      adenocarcinoma. Early detection of precursor lesions and subsequent treatment may
      prevent cancer development and this is possible with colonoscopy and biopsy.
      Inflammatory bowel disease-associated precursor lesions (dysplasia =
      intraepithelial neoplasia) must be distinguished from sporadic adenomas,
      occurring in non-colitic mucosa. Macroscopic lesions suspected of harbouring
      precursor lesions include irregular 'polypoid or elevated' lesions, which are
      usually broad-based and 'flat' lesions. Flat lesions are more common than
      elevated lesions and they are usually smaller. Chromoendoscopy increases the
      detection rate substantially as it allows targeted biopsies from suspicious
      lesions that increase the diagnostic yield of dysplasia. Ultimately, the
      combination of chromoendoscopy, or more advanced endoscopic techniques, and
      targeted biopsies may become the standard approach, rather than random biopsy
      sampling.

PMID- 16961747
TI  - Review article: colorectal cancer surveillance in ulcerative colitis - what
      should we be doing?
AB  - Different societies have published guidelines for colorectal cancer (CRC)
      surveillance in ulcerative colitis (UC). While it would seem that most
      gastroenterologists and endoscopists agree with these guidelines, different
      studies have shown that in clinical practice, the concept of dysplasia is not
      fully understood, and therefore, the guidelines are not always followed.
      According to some studies, the reason why gastroenterologists do not follow the
      recommendations is inadequate education. The main advance in recent years in this
      subject is in endoscopic diagnosis of dysplasia. The magnification and
      chromoendoscopy allow targeted biopsies to be taken. Some studies indicate that
      nontargeted biopsies are not useful in ruling out dysplasia. It is also important
      to realize that most dysplasia is visible in conventional colonoscopy. In
      colonoscopy, it is not only significant to detect dysplasia-associated lesions or
      masses; the endoscopist should also be trained to detect, in the course of
      conventional exploration, subtle changes in colour or in mucosal surfaces that
      imply dysplasia. Adherence to guidelines had been extensively assessed in other
      disease conditions (asthma, hypertension, etc.). According to our knowledge there
      are no such data regarding CRC surveillance in UC. Some barriers that may affect
      physicians include: (i) knowledge (lack of awareness or lack of familiarity);
      (ii) attitudes (lack of agreement, lack of self-efficacy, lack of outcome
      expectancy, or the inertia of previous practice) and (iii) behaviour (external
      barriers). In conclusion, we need new guidelines for CRC surveillance in UC,
      which must take into account the advances in risk factors of dysplasia and new
      technologies to study colon dysplasia.

PMID- 16961748
TI  - Review article: the effect of aminosalicylates and immunomodulation on cancer
      risk in inflammatory bowel disease.
AB  - Ulcerative colitis and, maybe to a similar extent, Crohn's disease are associated
      with an increased risk of colorectal carcinoma. As a consequence of this
      increased risk, surveillance strategies have been proposed to prevent colorectal
      carcinoma through early detection of dysplasia, which may herald malignant
      disease. These surveillance strategies are controversial for several reasons
      discussed in this review. It may be concluded from the relevant studies that
      regular use of at least 1.2 g of mesalazine per day may effectively prevent about
      two out of three colon cancers in ulcerative colitis. In contrast, there seems to
      be no role for either mercaptopurine or folic acid in protection from colon
      cancer.

PMID- 16961749
TI  - Review article: saving the colon in severe colitis - the case for medical
      therapy.
AB  - The choice between ciclosporin (CsA), infliximab (IFX) and surgery for severe
      colitis not responding to intensive intravenous treatment, is challenging. With
      the advent of vislizumab and alternatives such as tacrolimus or
      leucocytapheresis, decisions will get harder. This article reviews the evidence
      for each intervention, draws attention to disparities in the definition of severe
      colitis between different trials and gives practical guidance. Early medical
      decision making is critical. Standard intensive treatment with intravenous
      steroids is still the first-line approach. Progress should be monitored
      objectively using a simple predictive index. Rescue therapy with CsA (oral 5
      mg/kg or 2 mg/kg iv) or IFX (5 mg/kg) should be started on the third day of
      intensive treatment if predictive factors are poor (e.g. C-reactive protein > 45
      mg/L). Physicians should discuss with their patients that there is just one
      attempt at rescue therapy, because only one patient death, as a consequence of
      delayed colectomy, changes the balance of benefit between medicine and surgery.

PMID- 16961750
TI  - Review article: colon-saving medical therapy vs. colectomy in ulcerative colitis 
      the case for colectomy.
AB  - In the era of expanding medical therapy for ulcerative colitis, surgery is still
      a very valid option in those patients, where medicine is not able to control
      symptoms, both in the acute and chronic stages, and also for those at risk of
      developing a cancer. The ileal pouch-anal anastomosis (IPAA) will, for the vast
      majority of patients, give a very acceptable functional outcome. There is a risk
      of surgical complications and pouchitis; however, mortality is very low and
      compares well with medical therapy. Reduced female fertility is a concern but
      compared with the preoperative state, overall sexual function is largely
      improved. The ileorectal anastomosis is undergoing a revival and can be used
      especially in the case of female fertility concerns. Either the continent
      ileostomy or a conventional ileostomy is an option for those 10-15% of patients
      who will eventually experience pouch failure, usually either because of septic
      complications or an unacceptable bowel function. Quality of life following both
      these options, and IPAA, is excellent and does not differ from that of the
      matched background population.

PMID- 16961751
TI  - Review article: biological drugs in Crohn's disease.
AB  - Biological drugs have opened new therapeutic horizons for treating Crohn's
      disease (CD), but have also brought with them issues related to immunogenicity,
      long-term efficacy, safety and cost. At present, inhibitors tumour necrosis
      factor and adhesion molecules are the most advanced in use and development. When
      treating luminal disease with infliximab, two-thirds of patients respond
      initially. The ACCENT 1 study demonstrated that 28% of initial responders are in
      remission for 1 year. Infliximab has also had a major impact on the management of
      Crohn's anorectal fistulas. The ACCENT 2 study demonstrated initial response in
      two-thirds of patients. One-fifth of all treated patients were healed at 1 year.
      Infliximab diminished the need for further surgery. Magnetic resonance imaging
      scanning allows the extent of deep healing to be assessed and may influence the
      duration of treatment. The Mayo Clinic experience in 500 patients demonstrated 6%
      serious adverse events related to infliximab. The TREAT registry will provide
      long-term safety data on a larger group of patients. Concurrent immunosuppressive
      drugs and pre-infusion steroids can decrease antibody formation to infliximab.
      Screening for tuberculosis (TB) diminishes the rate of TB activation. Biological
      drugs can offer great therapeutic benefit, but their use must be considered in
      context.

PMID- 16961752
TI  - Review article: the intestinal lumen as a therapeutic target in inflammatory
      bowel disease.
AB  - Undigested carbohydrates reaching the colon can act as competitors for epithelial
      bacterial receptors, making it difficult for noncommensal bacteria to adhere to
      them. On the contrary, fermentation of these carbohydrates by anaerobic flora
      produces - among other substrates - butyrate that is involved in numerous
      important metabolic processes. These include the provision of energy to the
      colonocytes, the enhancement of sodium and water absorption and the synthesis of
      mucus and cell membranes. In addition, butyrate inhibits the nuclear
      translocation of the transcription factor NFkappaB, which exerts a potent anti
      inflammatory activity. Clinical experience with probiotics in inflammatory bowel
      disease (IBD) is controversial. Whereas some probiotic preparations appear to be
      useful in ulcerative colitis (UC) and pouchitis, most attempts to use probiotics
      for treating or preventing recurrence in Crohn's disease have failed. It should
      be pointed out that - unlike in the small bowel - the colon and ileal pouches are
      well-established microbiological ecosystems with increasing amounts of a wide
      variety of bacterial strains. These bacterial strains have a high degree of
      metabolic interaction with luminal nutrients and a greater probability of
      developing dysbiosis. With this in mind, the rationale for using pre- and
      probiotics appears to be stronger for colonic IBD (UC or Crohn's colitis) and
      pouchitis than for IBD mostly involving the small bowel.

PMID- 16961753
TI  - Can differences in breast cancer utilities explain disparities in breast cancer
      care?
AB  - BACKGROUND: Black, older, and less affluent women are less likely to receive
      adjuvant breast cancer therapy than their counterparts. Whereas preference
      contributes to disparities in other health care scenarios, it is unclear if
      preference explains differential rates of breast cancer care. OBJECTIVE: To
      ascertain utilities from women of diverse backgrounds for the different stages
      of, and treatments for, breast cancer and to determine whether a treatment
      decision modeled from utilities is associated with socio-demographic
      characteristics. PARTICIPANTS: A stratified sample (by age and race) of 156
      English-speaking women over 25 years old not currently undergoing breast cancer
      treatment. DESIGN AND MEASUREMENTS: We assessed utilities using standard gamble
      for 5 breast cancer stages, and time-tradeoff for 3 therapeutic modalities. We
      incorporated each subject's utilities into a Markov model to determine whether
      her quality-adjusted life expectancy would be maximized with chemotherapy for a
      hypothetical, current diagnosis of stage II breast cancer. We used logistic
      regression to determine whether socio-demographic variables were associated with
      this optimal strategy. RESULTS: Median utilities for the 8 health states were:
      stage I disease, 0.91 (interquartile range 0.50 to 1.00); stage II, 0.75 (0.26 to
      0.99); stage III, 0.51 (0.25 to 0.94); stage IV (estrogen receptor positive),
      0.36 (0 to 0.75); stage IV (estrogen receptor negative), 0.40 (0 to 0.79);
      chemotherapy 0.50 (0 to 0.92); hormonal therapy 0.58 (0 to 1); and radiation
      therapy 0.83 (0.10 to 1). Utilities for early stage disease and treatment
      modalities, but not metastatic disease, varied with socio-demographic
      characteristics. One hundred and twenty-two of 156 subjects had utilities that
      maximized quality-adjusted life expectancy given stage II breast cancer with
      chemotherapy. Age over 50, black race, and low household income were associated
      with at least 5-fold lower odds of maximizing quality-adjusted life expectancy
      with chemotherapy, whereas women who were married or had a significant other were
      4-fold more likely to maximize quality-adjusted life expectancy with
      chemotherapy. CONCLUSIONS: Differences in utility for breast cancer health states
      may partially explain the lower rate of adjuvant therapy for black, older, and
      less affluent women. Further work must clarify whether these differences result
      from health preference alone or reflect women's perceptions of sources of
      disparity, such as access to care, poor communication with providers, limitations
      in health knowledge or in obtaining social and workplace support during therapy.

PMID- 16961754
TI  - Description of a research-based health activism curriculum for medical students.
AB  - INTRODUCTION: Few curricula train medical students to engage in health system
      reform. AIM: To develop physician activists by teaching medical students the
      skills necessary to advocate for socially equitable health policies in the U.S.
      health system. SETTING: Montefiore Medical Center, the University Hospital of the
      Albert Einstein College of Medicine, Bronx, NY. PROGRAM DESCRIPTION: We designed
      a 1-month curriculum in research-based health activism to develop physician
      activists. The annual curriculum includes a student project and 4 course
      sections;health policy, research methods, advocacy, and physician activists as
      role models; taught by core faculty and volunteers from academic institutions,
      government, and nongovernmental organizations. PROGRAM EVALUATION: From 2002 to
      2005, 47 students from across the country have participated. Students reported
      improved capabilities to generate a research question, design a research
      proposal,and create an advocacy plan. DISCUSSION: Our curriculum demonstrates a
      model for training physician activists to engage in health systems reform.

PMID- 16961757
TI  - The genetic of alcoholism: learning from 50 years of research.

PMID- 16961758
TI  - Alcohol-related genes: contributions from studies with genetically engineered
      mice.
AB  - Since 1996, nearly 100 genes have been studied for their effects related to
      ethanol in mice using genetic modifications including gene deletion, gene
      overexpression, gene knock-in, and occasionally by studying existing mutants.
      Nearly all such studies have concentrated on genes expressed in brain, and the
      targeted genes range widely in their function, including most of the principal
      neurotransmitter systems, several neurohormones, and a number of signaling
      molecules. We review 141 published reports of effects (or lack thereof) of 93
      genes on responses to ethanol. While most studies have focused on ethanol self
      administration and reward, and/or sedative effects, other responses studied
      include locomotor stimulation, anxiolytic effects, and neuroadaptation
      (tolerance, sensitization, withdrawal). About 1/4 of the engineered mutations
      increase self-administration, 1/3 decrease it, and about 40% have no significant
      effect. In many cases, the effects on self-administration are rather modest
      and/or depend on the specific experimental procedures. In some cases, genes in
      the background strains on which the mutant is placed are important for results.
      Not surprisingly, review of the systems affected further supports roles for
      serotonin, gamma-aminobutyric acid, opioids and dopamine, all of which have long
      been foci of alcohol research. Novel modulatory effects of protein kinase C and G
      protein-activated inwardly rectifying K+ (GIRK) channels are also suggested. Some
      newer research with cannabinoid systems is promising, and has led to ongoing
      clinical trials.

PMID- 16961759
TI  - The alcohol-preferring P rat and animal models of excessive alcohol drinking.
AB  - The alcohol-preferring, P, rat was developed by selective breeding to study
      ethanol drinking behavior and its consequences. Characterization of this line
      indicates the P rat meets all of the criteria put forth for a valid animal model
      of alcoholism, and displays, relative to their alcohol-non-preferring, NP,
      counterparts, a number of phenotypic traits associated with alcohol abuse and
      alcoholism. Behaviorally, compared with NP rats, P rats are less sensitive to the
      sedative and aversive effects of ethanol and more sensitive to the stimulatory
      effects of ethanol. Neurochemically, research with the P line indicates the
      endogenous dopaminergic, serotonergic, GABAergic, opiodergic, and peptidergic
      systems may be involved in a predisposition for alcohol abuse and alcoholism.
      Paralleling the clinical literature, genetically selected P rats display levels
      of ethanol intake during adolescence comparable to that seen during adulthood.
      Binge drinking has been associated with an increased risk for health and other
      problems associated with ethanol abuse. A model of binge-like drinking during the
      dark cycle indicates that P rats will consume 6 g/kg/day of ethanol in as little
      as three 1-hour access periods/day, which approximates the 24-hour intake of P
      rats with free-choice access to a single concentration of ethanol. The alcohol
      deprivation effect (ADE) is a transient increase in ethanol intake above baseline
      values upon re-exposure to ethanol access after an extended period of
      deprivation. The ADE has been proposed to be an animal model of relapse behavior,
      with the adult P rat displaying a robust ADE after prolonged abstinence. Overall,
      these findings indicate that the P rat can be effectively used in models
      assessing alcohol-preference, a genetic predisposition for alcohol abuse and/or
      alcoholism, and excessive drinking using protocols of binge-like or relapse-like
      drinking.

PMID- 16961760
TI  - The alcohol-preferring AA and alcohol-avoiding ANA rats: neurobiology of the
      regulation of alcohol drinking.
AB  - The AA (alko, alcohol) and ANA (alko, non-alcohol) rat lines were among the
      earliest rodent lines produced by bidirectional selection for ethanol preference.
      The purpose of this review is to highlight the strategies for understanding the
      neurobiological factors underlying differential alcohol-drinking behavior in
      these lines. Most early work evaluated functioning of the major neurotransmitter
      systems implicated in drug reward in the lines. No consistent line differences
      were found in the dopaminergic system either under baseline conditions or after
      ethanol challenges. However, increased opioidergic tone in the ventral striatum
      and a deficiency in endocannabinoid signaling in the prefrontal cortex of AA rats
      may comprise mechanisms leading to increased ethanol consumption. Because complex
      behaviors, such as ethanol drinking, are not likely to be controlled by single
      factors, system-oriented molecular-profiling strategies have been used recently.
      Microarray based expression analysis of AA and ANA brains and novel data-mining
      strategies provide a system biological view that allows us to formulate a
      hypothesis on the mechanism underlying selection for ethanol preference. Two main
      factors appear active in the selection: a recruitment of signal transduction
      networks, including mitogen-activated protein kinases and calcium pathways and
      involving transcription factors such as Creb, Myc and Max, to mediate ethanol
      reinforcement and plasticity. The second factor acts on the mitochondrion and
      most likely provides metabolic flexibility for alternative substrate utilization
      in the presence of low amounts of ethanol.

PMID- 16961761
TI  - The UChA and UChB rat lines: metabolic and genetic differences influencing
      ethanol intake.
AB  - Ethanol non-drinker (UChA) and drinker (UChB) rat lines derived from an original
      Wistar colony have been selectively bred at the University of Chile for over 70
      generations. Two main differences between these lines are clear. (1) Drinker rats
      display a markedly faster acute tolerance than non-drinker rats. In F2 UChA x
      UChB rats (in which all genes are 'shuffled'), a high acute tolerance of the
      offspring predicts higher drinking than a low acute tolerance. It is further
      shown that high-drinker animals 'learn' to drink, starting from consumption
      levels that are one half of the maximum consumptions reached after 1 month of
      unrestricted access to 10% ethanol and water. It is likely that acquired
      tolerance is at the basis of the increases in ethanol consumption over time. (2)
      Non-drinker rats carry a previously unreported allele of aldehyde dehydrogenase-2
      (Aldh2) that encodes an enzyme with a low affinity for Nicotinamide-adenine
      dinuclectide (NAD+) (Aldh2(2)), while drinker rats present two Aldh2 alleles
      (Aldh2(1) and Aldh2(3)) with four- to fivefold higher affinities for NAD+.
      Further, the ALDH2 encoded by Aldh2(1) also shows a 33% higher Vmax than those
      encoded by Aldh2(2) and Aldh2(3). Maximal voluntary ethanol intakes are the
      following: UChA Aldh2(2)/Aldh2(2) = 0.3-0.6 g/kg/day; UChB Aldh2(3)/Aldh2(3) =
      4.5-5.0 g/kg/day; UChB Aldh2(1)/Aldh2(1) = 7.0-7.5 g/kg/day. In F2 offspring of
      UChA x UChB, the Aldh2(2)/Aldh2(2) genotype predicts a 40-60% of the alcohol
      consumption. Studies also show that the low alcohol consumption phenotype of
      Aldh2(2)/Aldh2(2) animals depends on the existence of a maternally derived low
      activity mitochondrial reduced form of nicotinamide-adenine-dinucleotide (NADH)
      ubiquinone complex I. The latter does not influence ethanol consumption of
      animals exhibiting an ALDH2 with a higher affinity for NAD+. An illuminating
      finding is the existence of an 'acetaldehyde burst' in animals with a low
      capacity to oxidize acetaldehyde, being fivefold higher in UChA than in UChB
      animals. We propose that such a burst results from a great generation of
      acetaldehyde by alcohol dehydrogenase in pre-steady-state conditions that is not
      met by the high rate of acetaldehyde oxidation in mitochondria. The acetaldehyde
      burst is seen despite the lack of differences between UChA and UChB rats in
      acetaldehyde levels or rates of alcohol metabolism in steady state. Inferences
      are drawn as to how these studies might explain the protection against alcoholism
      seen in humans that carry the high-activity alcohol dehydrogenase but metabolize
      ethanol at about normal rates.

PMID- 16961762
TI  - Phenotypic characterization of genetically selected Sardinian alcohol-preferring
      (sP) and -non-preferring (sNP) rats.
AB  - Sardinian alcohol-preferring (sP) and -non-preferring (sNP) rats are one of the
      pairs of rat lines selectively bred for high and low alcohol preference and
      consumption, respectively, under the homecage, continuous two-bottle choice
      regimen. sP rats meet most of the fundamental criteria for an animal model of
      alcoholism, in that they voluntarily consume sufficient amounts of alcohol to
      achieve significant blood alcohol levels and produce psychopharmacological
      effects, including anxiolysis and motor stimulation. sP rats are also willing to
      'work' (such as lever-pressing) for alcohol. Chronic alcohol drinking in sP rats
      results in the development of tolerance to a given effect of alcohol
      (specifically, motor incoordination) and relapse-like drinking (the alcohol
      deprivation effect). Conversely, sNP rats avoid alcohol virtually completely;
      their avoidance for alcohol being resistant even to an environmental manipulation
      such as long-term exposure to alcohol plus sucrose. sP and sNP rats have been
      characterized for different phenotypes, possibly associated to their different
      alcohol preference and consumption. In comparison with sNP rats, alcohol-naive sP
      rats displayed (1) more anxiety-related behaviors; (2) higher initial sensitivity
      to the locomotor stimulating and sedative/hypnotic effects of alcohol; and (3)
      lower sensitivity to the aversive effects of alcohol. The present paper reviews
      the data collected to date on alcohol drinking behavior and other alcohol-related
      behaviors in sP and sNP rats. The behavioral profile of sP rats is also compared
      with that of other lines of selectively bred alcohol-preferring rats and the
      heterogeneity resulting from this comparison is discussed in terms of different
      animal models for the different forms of alcoholism.

PMID- 16961763
TI  - Genetically selected Marchigian Sardinian alcohol-preferring (msP) rats: an
      animal model to study the neurobiology of alcoholism.
AB  - The present article provides an up-to-date review summarizing almost 18 years of
      research in genetically selected Marchigian Sardinian alcohol-preferring (msP)
      rats. The results of this work demonstrate that msP rats have natural preference
      for ethanol characterized by a spontaneous binge-type of drinking that leads to
      pharmacologically significant blood ethanol levels. This rat line is highly
      vulnerable to relapse and presentation of stimuli predictive of alcohol
      availability or foot-shock stress can reinstate extinguished drug-seeking up to 8
      months from the last alcohol experience. The msP rat is highly sensitive to
      stress, shows an anxious phenotype and has depressive-like symptoms that recover
      following ethanol drinking. Interestingly, these animals have an up-regulated
      corticotrophin releasing factor (CRF) receptor 1 system. Clinical studies have
      shown that alcoholic patients often drink ethanol in the attempt to self-medicate
      from negative affective states and to search for anxiety relief. We propose that
      msP rats represent an animal model that largely mimics the human alcoholic
      population that due to poor ability to engage in stress-coping strategies drink
      ethanol as a tension relief strategy and for self-medication purposes.

PMID- 16961764
TI  - Modulation of high alcohol drinking in the inbred Fawn-Hooded (FH/Wjd) rat
      strain: implications for treatment.
AB  - The Fawn-Hooded rat (FH/Wjd) is an inbred alcohol-preferring rat strain, unlike
      most of the other strains that were selectively bred for high alcohol intake and
      preference. It was chosen for study some 16 years ago because of a reported
      mutation that disrupted platelet serotonin function. Although the FH/Wjd rat has
      high alcohol intake (>5 g/kg/day) and preference (>65%), interbreeding with an
      alcohol-non-preferring inbred strain suggested that these measures are unrelated
      to the serotonin abnormality. Similarly, the exaggerated immobility of the FH/Wjd
      rats in the forced swim test did not correlate with the high alcohol intake. Many
      compounds have been tested in the FH/Wjd rats after both acute and chronic
      treatment and a substantial number of them have proved effective. However, as the
      case with opiate antagonists, tolerance to the effects of the drug can develop.
      An up-regulation of opioid receptors accompanied the chronic treatment and this
      mechanism may account for the development of tolerance. Tolerance to opiate
      antagonists has also been demonstrated in two of the selectively bred alcohol
      preferring rat lines, but it is unknown whether this process may contribute to
      the relapses seen in individuals being treated with naltrexone. Other drugs that
      reliably decrease alcohol intake in the FH/Wjd rats include the 5
      hydroxytryptamine-2A receptor antagonist, amperozide, the mGlu5 receptor
      antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) and herbal
      derivatives such as ibogaine, St. John's wort and kudzu extract. Thus, studies in
      the FH/Wjd rat have led to the discovery of a wide variety of targets for the
      development of novel agents to treat alcoholism. The fact that several of these
      drugs were shown to reduce alcohol intake in some of the selectively bred alcohol
      preferring rat lines and/or alcohol-preferring vervet monkeys increases our
      confidence that they are good candidates for further development.

PMID- 16961765
TI  - Non-human primate models of inheritance vulnerability to alcohol use disorders.
AB  - Many animal species have been used to model certain aspects of alcohol use and
      addiction. However, there are complex behavioral and social features of alcohol
      use disorders that are not easily modeled in animal species. This review
      considers both the limitations and advantages of using a non-human primate to
      model alcohol use disorders and discusses how non-human primates can be
      particularly useful for studying how genetic variants interact with social
      factors, temperament and alcohol response as motivating factors for alcohol
      consumption and abstinence. Genetic variants in rhesus macaques (Macaca mulatta)
      that are functionally equivalent to those increasing addiction vulnerability in
      humans influence temperament, stress reactivity and alcohol response in addition
      to voluntary alcohol consumption. Non-human primate models may also have
      translational value for understanding of how variants within addiction and abuse
      vulnerability genes influence alcohol-induced neuroadaptation, neuropathology and
      treatment response.

PMID- 16961766
TI  - The genetics of alcoholism: identifying specific genes through family studies.
AB  - Alcoholism is a complex disorder with both genetic and environmental risk
      factors. Studies in humans have begun to elucidate the genetic underpinnings of
      the risk for alcoholism. Here we briefly review strategies for identifying
      individual genes in which variations affect the risk for alcoholism and related
      phenotypes, in the context of one large study that has successfully identified
      such genes. The Collaborative Study on the Genetics of Alcoholism (COGA) is a
      family-based study that has collected detailed phenotypic data on individuals in
      families with multiple alcoholic members. A genome-wide linkage approach led to
      the identification of chromosomal regions containing genes that influenced
      alcoholism risk and related phenotypes. Subsequently, single nucleotide
      polymorphisms (SNPs) were genotyped in positional candidate genes located within
      the linked chromosomal regions, and analyzed for association with these
      phenotypes. Using this sequential approach, COGA has detected association with
      GABRA2, CHRM2 and ADH4; these associations have all been replicated by other
      researchers. COGA has detected association to additional genes including GABRG3,
      TAS2R16, SNCA, OPRK1 and PDYN, results that are awaiting confirmation. These
      successes demonstrate that genes contributing to the risk for alcoholism can be
      reliably identified using human subjects.

PMID- 16961767
TI  - Targeting treatments for alcohol dependence: the pharmacogenetics of naltrexone.
AB  - Alcohol dependence is one of the leading causes of morbidity worldwide, yet only
      a minority of those afflicted engages in treatment. While increasing access to
      treatment is an important public health approach, increasing the success of
      treatment is also likely to lead to greater engagement. However, alcohol
      dependence is a complex disorder likely to consist of several biological
      subtypes. Recent evidence from a number of different studies has suggested that
      genetic variation in the mu-opioid receptor has a significant influence on
      clinical presentation of alcohol problems and response to treatment with an
      opioid antagonist. Most notably, the A118G polymorphism of the mu-receptor gene
      has been demonstrated to predict clinical response to naltrexone in alcohol
      dependent individuals. This article reviews the biological correlates and
      outlines a scientific agenda for better understanding the role of opioid
      neurotransmission in the etiology, maintenance and treatment of alcohol
      dependence.

PMID- 16961768
TI  - Microarrays: a monitoring tool for transplant patients?
AB  - Microarray technology holds a distinct advantage over traditional genomic
      methods, with the unique capability to rapidly generate multiple global gene
      expression profiles in parallel. This technology is quickly gaining widespread
      use in many areas of science and medicine because it can be easily adapted to
      study many experimental questions, particularly relating to disease
      heterogeneity. Microarray experiments have begun to advance our understanding of
      the underlying molecular processes in solid organ transplantation; however,
      several obstacles must be overcome before this technology is ready for
      application in the clinical setting. This article will review the current
      applications of microarray technology in the field of transplantation, and
      discuss the potential impact of this technology on monitoring of solid organ
      transplant recipients.

PMID- 16961769
TI  - Thrombotic microangiopathy after kidney transplantation.
AB  - Two forms of post-transplant thrombotic microangiopathy (TMA) may be recognized:
      recurrent TMA and de novo TMA. Recurrent TMA may occur in patients who developed
      a nondiarrhoeal form of haemolytic uraemic syndrome (HUS) being particularly
      frequent in patients with autosomal recessive or dominant HUS. The recurrence is
      almost the rule in patients with mutation in complement factor H gene. Most
      patients eventually lose the graft. Treatment with plasma infusions or
      plasmapheresis is often disappointing, but few cases may be rescued. Intravenous
      immunoglobulins and rituximab have also been successful in anedoctic cases. De
      novo TMA is rarer. A number of factors including viral infection may be
      responsible of de novo TMA, but in most cases TMA is triggered by calcineurin
      inhibitors or mTOR inhibitors. The clinical presentation of de novo TMA may be
      variable with some patients showing clinical and laboratory features of HUS while
      others showing only a progressive renal failure. The prognosis is less severe
      than with recurrent TMA. Complete withdrawal of the offending drug may lead to
      improvement in many cases. The addition of plasma exchange may result in graft
      salvage in about 80% of cases.

PMID- 16961770
TI  - Conventional versus piggyback technique of caval implantation; without extra
      corporeal veno-venous bypass. A comparative study.
AB  - Conventional orthotopic liver transplantation (CON-LT) involves resection of
      recipient cava, usually with extra-corporeal circulation (veno-venous bypass,
      VVB), while in the piggyback technique (PC-LT) the cava is preserved. Along with
      a temporary portacaval shunt (TPCS), better haemodynamic maintenance is purported
      with PC-LT. A prospective, consecutive series of 384 primary transplants (2000
      2003) were analysed, 138 CON-LT (with VVB) and 246 PC-LT (54 without TPCS).
      Patient/donor characteristics were similar in the two groups. PC-LT required less
      usage of fresh-frozen plasma and platelets, intensive care stay, number of
      patients requiring ventilation after day 1 and total days spent on ventilator.
      The results were not different when comparing, total operating and warm ischaemia
      time (WIT), red cell usage, requirement for renal support, day 3 serum creatinine
      and total hospital stay. TPCS had no impact on outcome other than WIT (P = 0.02).
      Three patients in PC-LT group (three of 246;1.2%) developed caval outflow
      obstruction (P = 0.02). There was no difference in short- or long-term graft or
      patient survival. PC-LT has an advantage over CON-LT unsing VVB with respect to
      intraoperative blood product usage, postoperative ventilation requirement and ITU
      stay. VVB is no longer required and TPCS may be used selectively in adult
      transplantation.

PMID- 16961771
TI  - Comparing two ureter reimplantation techniques in kidney transplant recipients.
AB  - We compared the incidence of urological and anastomotic complications for the
      ureteroureterostomy and Lich-Gregoir techniques in kidney transplant recipients.
      Between May 2003 and February 2004, 75 kidney transplant recipients from living
      donors were divided into two similar groups to receive ureteroureterostomy (n =
      41, 28 male, 13 female) and Lich-Gregoir techniques (n = 34, 24 male, 10 female)
      for ureteral reimplantation. Patients with vesicoureteral reflux (VUR) to the
      native kidneys were excluded from the study. The urological complications
      included complicated hematuria, ureteral stenosis, symptomatic VUR, recurrent
      urinary tract infection (UTI). There was no statistical significance between two
      groups in terms of gender, age, end-stage renal disease etiology, human leucocyte
      antigen (HLA) mismatch numbers, type and duration of dialysis, and cold ischemia
      time. The incidence of urologic and anastomotic complications was 12%.
      Complications in the Lich-Gregoir group included symptomatic VUR in 8.8% and
      stent migration in 2.9% of cases. Complications observed in the
      ureteroureterostomy group were ureteral stricture 7.3% and complicated hematuria
      in 4.9% of cases. However, symptomatic reflux was not observed in the
      ureteroureterostomy group. UTI frequency was similar in both groups.
      Ureteroureterostomy can be safely performed as a primary choice in kidney
      transplant recipients.

PMID- 16961772
TI  - Hepatic steatosis is associated with intrahepatic cholestasis and transient
      hyperbilirubinemia during regeneration after living donor liver transplantation.
AB  - A clear understanding of the mechanisms in steatotic livers that trigger
      cholestasis or hyperbilirubinemia after living donor liver transplantation (LDLT)
      remains elusive. We hypothesized that microarchitectural disturbance might occur
      within regenerating steatotic livers without impairment of hepatic proliferative
      activity. Liver biopsy specimens from 67 LDLT recipients taken at the 10th
      postoperative day were scored for the numbers of portal tracts per area (nPT/A)
      of liver tissue and for intrahepatic cholestasis, and immunostained by
      proliferating cell nuclear antigen (PCNA) and Ki-67. The preoperative degree of
      macrovesicular steatosis (MaS) was independently associated with cholestasis
      after LDLT (P < 0.001). Serum total bilirubin results on the 1st, 3rd, and 7th
      days post-LDLT in MaS+ (5-30% of MaS; n = 37) patients were significantly higher
      than those in MaS- (<5% of MaS; n = 30) patients (P = 0.030, 0.042, and 0.019,
      respectively). Mean numbers of positively stained hepatocytes were 53.1 +/- 12.0
      in patients with MaS and 48.0 +/- 17.1 in those without MaS by PCNA (P = 0.390),
      and 24.4 +/- 10.5 and 24.0 +/- 14.0 by Ki-67 (P = 0.940). However, a significant
      negative correlation was found between the degree of MaS and nPT/A (P = 0.013),
      and nPT/A was correlated with the grade of histological cholestasis (r = 0.350, P
      = 0.039). Intrahepatic cholestasis and hyperbilirubinemia after LDLT could be
      caused by scanty morphologic change of portal tract during steatotic liver
      regeneration.

PMID- 16961773
TI  - Long-term results (10 years) of a prospective trial comparing Lo-tact-1
      monoclonal antibody and anti-thymocyte globulin induction therapy in kidney
      transplantation.
AB  - To evaluate long-term patient and graft survival, and the incidence of acute and
      chronic rejection, infectious diseases and malignancies following induction
      therapy with a rat monoclonal interleukin 2 receptor antibody, Lo-Tact-1, or anti
      thymocyte globulin (ATG). Forty first-time kidney transplant patients were
      prospectively randomized to two groups between May 1990 and June 1991. Twenty
      recipients were treated with Lo-Tact-1 (group 1) and the other 20, with ATG
      (group 2) during the first 14 days of the transplantation protocol. All patients
      were treated with azathioprine, steroids and cyclosporin A. Data were collected
      over 10 years. Median age was 42.1 years in group 1 and 39.3 years in group 2.
      Six recipients died during the 10 years of follow-up. All had functioning grafts.
      Death-censored graft survival was 35% in group 1 and 45% in group 2 after 10
      years (P = NS). The number of acute rejection was similar in the two groups.
      Chronic allograft rejection was significantly more frequent in group 2 (n = 9)
      than in group 1 (n = 3), P < 0.05. Viral and bacterial infections were more
      frequent in group 2 than in group 1 (respectively 8 vs. 2 and 16 vs. 10, P <
      0.05). Three patients had cancer. Although both Lo-tact-1 and ATG effectively
      prevented acute renal rejection, fewer bacterial and viral infections and cases
      of chronic allograft rejection were observed in Lo-tact-1-treated patients after
      10 years of follow-up, demonstrating the potential value of this treatment for
      kidney transplantation.

PMID- 16961774
TI  - The calcineurin activity profiles of cyclosporin and tacrolimus are different in
      stable renal transplant patients.
AB  - Cyclosporin and tacrolimus remain the cornerstone immunosuppressive drugs in
      organ transplantation. Dosing and monitoring these drugs is based on
      pharmacokinetic protocols, but measuring a pharmacodynamic parameter, calcineurin
      phosphatase (CaN) activity, could be a valuable supplement in determining optimal
      doses. Forty stable renal transplant patients were investigated three times in a
      6-month period. Blood samples were drawn at 0, 1, 2, 3 and 4 h after oral intake
      of tacrolimus (FK) or cyclosporin at days 1 and 180. At day 90, one blood sample
      at trough level (FK) or C2 level (cyclosporin A, CsA) was drawn. CaN activity was
      determined in whole blood as the release of 32P from a phosphorylated peptide.
      Activity of the 32P was quantitated by liquid scintillation and results converted
      to Units CaN, utilizing a calibration curve with CaN. We demonstrated that
      calcineurin activity profiles at days 1 and 180 were the same for both drugs.
      Furthermore, we found that patients treated with tacrolimus or cyclosporin
      displayed different calcineurin activity profiles. We found that cyclosporin
      displayed greater calcineurin inhibition than tacrolimus. We have demonstrated
      that the two drugs exert significantly different effects on calcineurin activity
      in renal transplant patients with stable, well-functioning grafts and that
      tacrolimus-treated patients can maintain good, stable graft function with minimal
      CaN inhibition.

PMID- 16961775
TI  - Hepatitis B virus immunization with an adjuvant containing vaccine after liver
      transplantation for hepatitis B-related disease: failure of humoral and cellular
      immune response.
AB  - Long-term hepatitis B reinfection prophylaxis after liver transplantation with
      hepatitis B immunoglobulin (HBIG) and nucleoside analogues is expensive and
      inconvenient. Studies evaluating humoral immune responses to hepatitis B virus
      (HBV) vaccines showed conflicting results. Best results were achieved under
      continuous HBIG administration with an adjuvant-containing HBsAg vaccine. In the
      present study, 8 patients who had been HBsAg positive and HBV DNA negative prior
      to liver transplantation were immunized with HBsAg-vaccine containing the
      adjuvant 3-deacylated monophosphoryl-lipid-A. Vaccination was started after
      discontinuation of HBIG. Six vaccinations were administered at weeks 0, 2, 4, 12,
      16 and 24. Humoral (anti-HBs titres) and cellular (enzyme-linked immunospot assay
      and fluorescence-activated cell sorting analysis) immune responses were studied.
      Only one of eight patients responded with a humoral immune response (maximum anti
      HBs titre 561 U/l). In this patient, decrease of anti-HBs titre before
      vaccination was significantly slower than in the other seven patients and anti
      HBs did not become negative before first vaccination. A T-cell response to HBsAg
      could not be detected in any of the patients. The responder was the only patient
      who showed a T-cell response to HBcAg. In conclusion, the adjuvant-containing
      vaccine did not induce a humoral or a detectable cellular immune response in most
      patients. Patient-related preconditions and concomitant HBIG administration
      should be further investigated as possible predictors for response.

PMID- 16961776
TI  - Effect of rapamycin on renal ischemia-reperfusion injury in mice.
AB  - The aim of this study was to determine the effect of rapamycin on renal ischemia
      reperfusion injury (IRI) in mice. Renal IRI was induced in male BALB/c mice by
      clamping both renal pedicles for 45 min. The mice were treated with either
      vehicle or rapamycin (2 mg/kg/day) by oral gavage, starting 1 day before the IRI
      and continued daily till killing. The mice were killed on days 1, 3 and 7 after
      the operation. The severity of the renal IRI was assessed by serum creatinine
      levels and renal histology. Proliferation of renal tubular cells was quantified
      by immunohistochemical staining for proliferating cell nuclear antigen (PCNA).
      One day after the IRI, the serum creatinine levels of rapamycin-treated mice were
      significantly higher than those of the vehicle-treated mice. Kidney sections from
      rapamycin-treated mice showed more marked tubular damage and significantly lower
      number of PCNA-positive cells. The number of PCNA-positive cells in the rapamycin
      treated mice remained significantly lower on day 3 after the IRI. By day 7 after
      the IRI, the serum creatinine levels, renal histology and positive PCNA staining
      in the kidney sections became similar between the two treatment groups. We
      conclude that in this murine model of renal IRI, rapamycin treatment aggravates
      renal IRI during the first 3 days after the insult. This effect might be
      mediated, at least partly, through inhibition of renal tubular cell
      proliferation.

PMID- 16961777
TI  - Prolonged survival of rat whole-limb allografts treated with cyclophosphamide,
      granulocyte colony-stimulation factor and FK506.
AB  - We evaluated the efficacy of a new protocol using cyclophosphamide (CYP),
      granulocyte colony-stimulation factor (G-CSF) and FK506 to induce high level
      chimerism following rat whole-limb allotransplantation. The present study
      investigated the dose requirement and toxicity of CYP monotherapy in inducing
      stable bone marrow chimerism. Fifty-six whole-limb allotransplants from LacZ
      transgenic rats to LEW rats were performed. CYP at a dose of 100 mg to 200 mg/kg
      was injected 2 days before transplantation and G-CSF of 25 microg/kg/day was
      given for 4 days. FK506 was used for 28 days at 1 mg/kg/day. The level of
      chimerism was evaluated by semi-quantitative polymerase chain reaction. The
      survival of limb allografts in recipients treated with CYP of 150 mg/kg was
      significantly prolonged to 107 days. The onset of rejection was more prolonged to
      158 days in recipients with CYP of 200 mg/kg, with two of eight grafts surviving
      >1 year and three recipients (38%) showed chronic, nonlethal GVHD with a high
      level of bone marrow chimerism. Limb allografting could contribute to chimerism
      in the recipient. Pretreatment with CYP had the dose-dependent effects of
      prolonging the survival of limb allografts. A CYP dose of 200 mg/kg appears to
      significantly prolong limb graft survival but frequently causes chronic nonlethal
      GVHD in the longer surviving recipients.

PMID- 16961778
TI  - Liver transplantation for the treatment of nonresectable metastatic duodenal
      paraganglioma.

PMID- 16961782
TI  - One-year prevalence and socio-cultural aspects of chronic headache in Turkish
      immigrants and German natives.
AB  - The aim of this research was to study the prevalence of chronic headache (CH) and
      associated socio-cultural factors in Turkish immigrants and native Germans. Five
      hundred and twenty-three Turkish and German company employees were screened using
      a standard questionnaire. Those who suffered from headaches were also examined by
      a neurologist. Complete data were available for 471 (90%) subjects. Thirty-four
      participants (7.2%) had CH. Two independent factors for association with CH could
      be identified: overuse of acute headache medication (OR = 72.5; 95% CI 25.9
      202.9), and being a first-generation Turkish immigrant compared with native
      Germans (OR = 4.4; 95% CI 1.4-13.7). In contrast, the factor associated with
      chronic headache was not increased in second-generation Turkish immigrants.
      Medication overuse was significantly more frequent in first-generation Turkish
      immigrants (21.6%) compared with second-generation Turkish immigrants (3.3%) and
      native Germans (3.6%; chi(2) = 38.0, P < 0.001). First-generation Turkish
      immigrants did not contact headache specialists at all, compared with 2.8% of
      second-generation Turkish immigrants and 8.8% of native Germans (chi(2) = 118.4,
      P < 0.001). Likewise no first-generation Turkish immigrant suffering from CH
      received headache preventive treatment, compared with 6.6% of native Germans
      (chi(2) = 19.1, P = 0.014). The data from this cross-sectional study reveal a
      high prevalence of chronic headache as well as a very low utilization of adequate
      medical care in first-generation Turkish immigrants in Germany.

PMID- 16961783
TI  - Cervical spine joint hypermobility: a possible predisposing factor for new daily
      persistent headache.
AB  - The objective of this study was to suggest that joint hypermobility (specifically
      of the cervical spine) is a predisposing factor for the development of new daily
      persistent headache (NDPH). Twelve individuals (10 female, 2 male) with primary
      NDPH were evaluated by one of two physical therapists. Each patient was tested
      for active cervical range of motion and for the presence of excessive
      intersegmental vertebral motion in the cervical spine. All patients were screened
      utilizing the Beighton score, which determines degree of systemic hypermobility.
      Eleven of the 12 NDPH patients were found to have cervical spine joint
      hypermobility. Ten of the 12 NDPH patients had evidence of widespread joint
      hypermobility with the Beighton score. Based on our findings we suggest that
      joint hypermobility, specifically of the cervical spine, may be a predisposing
      factor for the development of NDPH.

PMID- 16961784
TI  - Blink reflex R2 amplitudes in cervicogenic headache, chronic tension-type
      headache and migraine.
AB  - Blink reflex R2 amplitude was investigated in seven patients with cervicogenic
      headache (CEH), 12 patients with chronic tension-type headache, 23 patients with
      migraine (10 with aura) and 17 headache-free controls. Standard electrical
      stimulation of the supraorbital nerve was applied and the response was recorded
      from the ipsilateral and the contralateral orbicularis oculi muscles. Low R2
      amplitude was found in CEH patients compared with control subjects. Headache is
      unilateral in CEH and the ipsilateral and contralateral responses after
      stimulation on the painful side were most depressed. R2 amplitude was not
      significantly affected in migraine and tension headache patients. The results
      suggest that lower brainstem excitability is reduced in CEH. A state of
      hypoactivity may be present in caudal trigeminal nucleus neurons on the
      symptomatic side.

PMID- 16961785
TI  - Discontinuation of medication overuse in headache patients: recovery of
      therapeutic responsiveness.
AB  - It is generally accepted that ongoing medication overuse nullifies the effect of
      prophylactic treatment, although few data support this contention. We set out to
      describe the treatment outcome in patients withdrawn from medication overuse and
      relate any improvement to a renewed effect of prophylaxis. For patients with
      probable medication-overuse headache (pMOH), treated and dismissed from the
      Danish Headache Centre in 2002 and 2003, we assed, from prospective headache
      diaries, the headache frequency before and after withdrawal of offending drugs
      and compared these frequencies with the headache frequency at dismissal. Among
      1326 patients, 337 had pMOH. Eligible were 175, mean age 49 years, male/female
      ratio 1 : 2.7. Overall, there was a 46% decrease in headache frequency from the
      first visit to dismissal (P < 0.0001). Patients with no improvement 2 months
      after complete drug withdrawal (N = 88) subsequently responded to pharmacological
      and/or non-pharmacological prophylaxis with a 26% decrease in headache frequency
      as measured from the end of withdrawal to dismissal (P < 0.0001). At dismissal,
      47% were on prophylaxis. Former non-responders to medical prophylaxis had a 49%
      decrease in headache frequency from first visit to dismissal (P < 0.0001),
      whereas those who had never received prophylaxis had a 56% reduction (P <
      0.0001). This difference was not statistically significant (P = 0.22). Almost all
      MOH patients benefit from drug withdrawal, either just from the withdrawal or by
      transformation from therapeutic non-responsiveness to responsiveness. According
      to the International Classification of Headache Disorders, 2nd edn, the MOH
      diagnosis requires improvement after drug withdrawal. Our data suggest that these
      diagnostic criteria are too strict.

PMID- 16961786
TI  - Zonisamide for migraine prophylaxis in refractory patients.
AB  - Zonisamide is a new antiepileptic drug with multiple mechanisms of action and a
      favourable pharmacokinetic profile. Preliminary data suggest that zonisamide may
      be effective in migraine prophylaxis. We evaluated the efficacy and tolerability
      of zonisamide for migraine prophylaxis in refractory patients. We reviewed the
      charts of adult patients with International Headache Society-defined episodic
      migraine (EM) or with transformed migraine (TM) according to the Silberstein
      Lipton criteria, who had been treated with zonisamide at our out-patient clinic
      for at least 60 days. Demographic data, zonisamide dosage and duration of
      treatment were collected and analysed. Headache frequency, attack duration,
      headache severity and headache-related disability before and after treatment
      initiation with zonisamide were compared. Thirty-three patients were included in
      the study (average age 43.9 +/- 8.4 years; 23 (70%) with TM and 10 (30%) with
      EM). The patients had failed an average of 6.2 migraine prophylactic drugs prior
      to zonisamide. The average zonisamide daily dose was 337.9 +/- 146.3 mg and the
      average duration of treatment was 186.4 +/- 174.0 days. The average number of
      days with headache per month was reduced in the entire study population from 20.7
      +/- 9.5 before zonisamide treatment to 18.0 +/- 11.3 after its initiation (P =
      0.06) [in TM from 24.7 +/- 7.3 to 21.0 +/- 10.7 (P = 0.06); in EM from 11.6 +/-
      7.6 to 11.0 +/- 9.7 (P = NS)]. No significant changes in other headache
      parameters were found. Fourteen patients (42.4%) reported adverse events (AEs),
      the most common of which was fatigue. Most patients (12/14, 85.7%) rated AEs as
      mild or moderate. In this group of refractory migraine patients, zonisamide
      therapy did not result in a statistically significant beneficial effect on
      headache or on associated symptoms.

PMID- 16961787
TI  - A prospective, open-label, long-term study of the efficacy and tolerability of
      topiramate in the prophylaxis of chronic tension-type headache.
AB  - This open study evaluates the effectiveness and safety of topiramate for the
      prophylaxis of chronic tension-type headache. Fifty-one patients were enrolled,
      of whom 46 completed 24 weeks of treatment with topiramate. Daily dosing was
      titrated from 25 mg to 100 mg by treatment week 4. The primary efficacy parameter
      was headache frequency at weeks 13-24 compared with baseline. Headache frequency
      declined from 23.50 +/- 5.32 days (baseline, mean, SD) to 12.58 +/- 6.28 days at
      weeks 13-24 (P < 0.0001), with frequency of severe headaches dropping from 8.18
      to 3.14 days (P < 0.0001). The average headache intensity dropped from 6.13 to
      2.07 on the visual analogue scale (P < 0.0001). These parameters were not
      significantly reduced at weeks 5-12. A 50% reduction in headache frequency was
      achieved in 73% of patients at weeks 13-24. Also improved were mood, sleep,
      quality of life (all parameters, P < 0.0001) as well as the Beck Depression
      Inventory-II (P < 0.0001). In addition, a highly significant weight loss of 2.14
      kg (mean) was observed between baseline (71.64 +/- 10.65 kg) and week 24 [69.50
      +/- 10.04 kg (SD)] (P < 0.0001). There were only few side-effects, none of these
      rated severe. The results provide preliminary confirmation of the efficacy and
      tolerability of topiramate in the prophylaxis of chronic tension-type headache.

PMID- 16961788
TI  - The prevalence of premonitory symptoms in migraine: a questionnaire study in 461
      patients.
AB  - Migraine attacks are often preceded by premonitory symptoms. Prevalence rates of
      migraine patients reporting one or more premonitory symptoms show considerable
      variability and rates range between 12% and 79%. Sources of variability might be
      differences in study population or research design. Using a questionnaire, we
      retrospectively studied the prevalence of 12 predefined premonitory symptoms in a
      clinic-based population. Of 461 migraine patients, 374 (81%) responded. At least
      one premonitory symptom was reported by 86.9% and 71.1% reported two or more. The
      most frequently reported premonitory symptoms were fatigue (46.5%), phonophobia
      (36.4%) and yawning (35.8%). The mean number of premonitory symptoms per person
      was 3.2 (+/- 2.5). Women reported 3.3 premonitory symptoms compared with 2.5
      symptoms in men (P = 0.01). Age, education, migraine subtype (with or without
      aura) and mean attack frequency had no effect on the mean number of symptoms per
      individual. In conclusion, premonitory symptoms are frequently reported by
      migraine patients. Sensitivity and specificity of premonitory symptoms for
      migraine need to be assessed using prospective methods.

PMID- 16961789
TI  - Functional gastrointestinal disorders in migrainous children: efficacy of
      flunarizine.
AB  - The aim of this study was to evaluate the prevalence of functional
      gastrointestinal disorders (FGIDs) in children with migraine headache and the
      effects of flunarizine on gastrointestinal manifestations. We studied 50
      migrainous children (mean age 8.63 years). The clinical pattern and the diagnosis
      of FGIDs were obtained from structured questionnaires. All subjects underwent
      measurement of total gastric emptying time (TGEt) performed by real-time
      ultrasonography of the gastric antrum at baseline (T0). In the second part of the
      study, we evaluated 10 migrainous children (mean age 9.8 years) with associated
      FGIDs. In these 10 patients, repeated TGEt evaluation together with a detailed
      symptom history was obtained after 1 (T1) and 2 months (T2) of treatment with
      flunarizine. Control groups were composed of 10 migrainous children without FGIDs
      (mean age 9.2 years) and nine sex- and age-matched healthy children.
      Gastrointestinal disorders were present in 70% of the patients. Migrainous
      children with FGIDs had significantly (P < 0.01) more prolonged TGEt than
      subjects without FGIDs. Prior to therapy, all migrainous children with FGIDs had
      prolongation of TGEt compared with controls (P < 0.05). Patients on flunarizine
      had a significant decrease in TGEt at both 1 (P < 0.01) and 2 months (P = 0.002)
      of therapy. The mean frequency of abdominal pain per month was significantly (P <
      0.001) reduced at T1 compared with T0. The mean frequency of vomiting per month
      was significantly decreased at T1 (P < 0.05) and even more so at T2 (P < 0.01).
      Finally, the mean frequency of headache per month was significantly reduced only
      at T2 (P < 0.05), whereas the mean duration of headache was significantly
      decreased at T1 (P < 0.01) with no difference between T1 and T2. Most children
      with migraine report FGIDs, associated with a delayed gastric emptying.
      Flunarizine decreases the frequency and duration of migrainous episodes as well
      as the gastrointestinal symptoms.

PMID- 16961790
TI  - Short-lasting headaches in children.
AB  - Short-lasting headaches have been studied infrequently in children and it is not
      known if the main categories of primary headaches of this type in adults are
      applicable to children. We report our experience with a group of 20 children with
      a brief headache. Two patients had a secondary headache. One patient had a
      headache with some clinical characteristics of paroxysmal hemicrania. The
      remaining 17 had a very brief headache. They were in many aspects comparable to
      others from previous studies on idiopathic stabbing headache in children: no
      associated symptoms, no other associated headache, frequent family history of
      migraine. They differed, however, in the younger age of the patients and the more
      frequent extratrigeminal location of the pain. Extratrigeminal ice-pick pain may
      be a variant of idiopathic stabbing headache, more prevalent in young children.

PMID- 16961791
TI  - Tryptophan depletion increases nausea, headache and photophobia in migraine
      sufferers.
AB  - Sensitivity to light was investigated 5 and 8 h after consumption of an amino
      acid drink which contained L-tryptophan (balanced amino acid condition: 19
      controls and 22 migraine sufferers) or which produced a short-term reduction in
      brain serotonin synthesis by omitting L-tryptophan (tryptophan depletion
      condition: 16 controls and 16 migraine sufferers). Migraine sufferers reported
      more intense nausea, headache, glare- and light-induced pain than controls. In
      addition, glare- and light-induced pain were greater in the tryptophan depletion
      condition than in the balanced amino acid condition, in both migraine sufferers
      and controls. Eight hours after the amino acid drink, after participants had
      completed tests of pain sensitivity and motion sickness provocation, tryptophan
      depletion augmented headache in migraine sufferers and aggravated nausea in
      migraine sufferers and controls. These findings suggest that a reduction in brain
      synthesis of serotonin intensifies photophobia and other migrainous symptoms and
      thus might contribute to the pathogenesis of migraine.

PMID- 16961792
TI  - Nummular headache: three new cases.
AB  - Nummular headache is proposed as a distinct type of headache in the Appendix of
      the second edition of the International Classification of Headache Disorders
      (ICHD-II). It is a chronic condition, with the following characteristics: pain is
      felt on a small circumscribed cranial area; pain is of mild to moderate
      intensity; there is no evidence of a structural abnormality. Herein, three cases
      fulfilling the ICHD-II proposed criteria (code A13.7.1) for nummular headache are
      reported.

PMID- 16961793
TI  - Medulloblastoma induces unusual headache with clinical picture of basilar-type
      migraine complicated by ischaemic infarcts.

PMID- 16961794
TI  - Ophthalmoplegic migraine presenting in infancy: a self-reported case.

PMID- 16961795
TI  - Is it a rational choice to treat with lumbar epidural blood patch headache caused
      by spontaneous cervical CSF leak?

PMID- 16961796
TI  - Acute migraine-associated borderzone cerebellar infarction.

PMID- 16961797
TI  - Association between chronic paroxysmal hemicrania and primary trochlear headache:
      pathophysiology and treatment.

PMID- 16961798
TI  - Ophthalmoplegic migraine: an unresolved problem.

PMID- 16961799
TI  - Acetylsalicylic acid, paracetamol and caffeine combination in headache.

PMID- 16961800
TI  - Medication overuse headache: type I and type II.

PMID- 16961802
TI  - A community-based study of Helicobacter pylori therapy using the strategy of
      test, treat, retest, and re-treat initial treatment failures.
AB  - BACKGROUND: Although eradication of Helicobacter pylori infection can decrease
      the risk of gastric cancer, the optimal regimen for treating the general
      population remains unclear. We report the eradication rate (intention-to-treat
      and per protocol) of a community-based H. pylori therapy using the strategy of
      test, treat, retest, and re-treat initial treatment failures. MATERIALS AND
      METHODS: In 2004, a total of 2658 residents were recruited for 13C-urea breath
      testing. Participants with positive results for infection received a standard 7
      day triple therapy (esomeprazole 40 mg once daily, amoxicillin 1 g twice daily,
      and clarithromycin 500 mg twice daily), and a 10-day re-treatment (esomeprazole
      40 mg once daily, amoxicillin 1 g twice daily, and levofloxacin 500 mg once
      daily) if the follow-up tests remained positive. Both H. pylori status and side
      effects were assessed 6 weeks after treatment. RESULTS: Among 886 valid
      reporters, eradication rates with initial therapy were 86.9% (95% confidence
      interval [CI]: 84.7-89.1%) and 88.7% (95%CI: 86.5-90.9%) by intention-to-treat
      and per protocol analysis, respectively. Re-treatment eradicated infection in
      91.4% (95%CI: 86-96.8%) of 105 nonresponders. Adequate compliance was achieved in
      798 (90.1%) of 886 subjects receiving the initial treatment and in all 105 re
      treated subjects. Mild side-effects occurred in 24% of subjects. Overall
      intention-to-treat and per protocol eradication rates were 97.7% (95%CI: 96.7
      98.7%) and 98.8% (95%CI: 98.5-99.3%), respectively, which were only affected by
      poor compliance (odds ratio, 3.3; 95%CI, 1.99-5.48; p < .0001). CONCLUSIONS: A
      comprehensive plan using drugs in which the resistance rate is low in a
      population combined with the strategy of test, treat, retest, and re-treat of
      needed can result in virtual eradication of H. pylori from a population. This
      provides a model for planning country- or region-wide eradication programs.

PMID- 16961803
TI  - Polymorphisms in cytokine genes and risk of Helicobacter pylori infection among
      Jamaican children.
AB  - BACKGROUND: Infection by Helicobacter pylori is often acquired during childhood.
      Recent studies suggest that inflammatory cytokines may play a role in
      susceptibility to, and disease phenotype caused by, H. pylori infection, but the
      association of host genetic variability with risk of H. pylori infection has not
      been studied in children. METHODS: We investigated the relationship between the
      risk of H. pylori antibody positivity and cytokine gene polymorphisms among 199
      two-year-old Jamaicans. H. pylori seropositivity was determined by a validated
      research enzyme-linked immunosorbent assay. Real-time Taqman polymerase chain
      reaction was used to determine variants at 17 loci in 11 cytokine genes (IL1A,
      IL1B, IL2, TNF, TLR4, IL4, IL6, IL10, IL10RA, IL12A and IL13). We estimated the
      odds ratio and the 95% confidence interval for the association of genetic
      polymorphisms with H. pylori seropositivity, using logistic regression. RESULTS:
      Forty (20.1%) of 199 children were seropositive. Children's H. pylori
      seropositivity correlated highly with maternal H. pylori seropositivity (OR =
      7.98, 95% CI = 1.05-60.60, p = .02). Children carrying IL1A-889T had a lower risk
      of H. pylori positivity, compared to those carrying -889C, with each T allele
      associated with 43% risk reduction (OR = 0.57, 95% CI = 0.33-0.99, p-trend =
      .05). No other loci we examined were associated with the risk of H. pylori
      seropositivity. CONCLUSIONS: The IL1A-889 T allele, known to express a higher
      level of cytokine IL-1alpha, is associated with a lower risk of H. pylori
      infection among Jamaican children. Our finding supports the hypothesis that an
      upregulation of pro-inflammatory cytokines may protect against persistent H.
      pylori colonization.

PMID- 16961804
TI  - Helicobacter pylori recurrence in patients with duodenal ulcer: Clinical,
      endoscopic, histologic, and genotypic aspects. A 10-year Brazilian series.
AB  - BACKGROUND: Recurrence infection following successful eradication of Helicobacter
      pylori is usually low, except for countries with high prevalence of H. pylori.
      The aim of this study was to verify H. pylori recurrence rate in patients with
      duodenal ulcer after eradication and the possible relationship with environmental
      factors, histologic pattern of the mucosa and bacterial genotype. MATERIALS AND
      METHODS: One-hundred and ninety-four patients with an active duodenal ulcer and
      who were successfully treated for H. pylori infection from 1990 to 1999 were
      studied. A questionnaire was answered about their living conditions, and a 14C
      urea breath test was performed. Patients with a positive breath test underwent an
      upper endoscopy to investigate for possible ulcer recurrence; gastric biopsy
      samples were than collected for rapid urease test and for histologic assessment.
      H. pylori vacA and cagA genotype was determined by polymerase chain reaction in
      those samples with positive urease test. RESULTS: H. pylori infection was
      detected in 11 patients (recurrence rate of 5.7%) that were not associated with
      the type of bacterial virulence. In 10 patients the ulcer was healed and all of
      them were clinically asymptomatic. In eight, histology showed an intensification
      of gastritis. All 11 patients had adequate housing and sanitary conditions and no
      other risk for H. pylori recurrence was identified. CONCLUSIONS: The recurrence
      rate of H. pylori in Brazil was higher than that reported in developed countries,
      but lower than usually reported in developing ones. Ulcer relapse rarely occurs
      even in long-term follow up.

PMID- 16961805
TI  - Comparison of amoxicillin-metronidazole plus famotidine or lansoprazole for
      amoxicillin-clarithromycin-proton pump inhibitor treatment failures for
      Helicobacter pylori infection.
AB  - BACKGROUND: Proton pump inhibitor-amoxicillin-metronidazole is recommended as
      second-line Helicobacter pylori therapy in Japan. The authors assessed the
      efficacy and safety of second-line eradication using the H2-receptor antagonist
      famotidine as a substitute for proton pump inhibitor. MATERIALS AND METHODS:
      Sixty-one patients who failed in first-line H. pylori eradication using proton
      pump inhibitor-clarithromycin-amoxicillin were randomly assigned to either second
      line therapy including metronidazole: a 7-day course of lansoprazole 30 mg,
      amoxicillin 750 mg, and metronidazole 250 mg, b.i.d. (lansoprazole group); or a 7
      day course of famotidine 40 mg, amoxicillin 750 mg, and metronidazole 250 mg,
      b.i.d. (famotidine group). Eradication was assessed for each group at least 4
      weeks after completing eradication therapy. Drug susceptibility test was
      performed using 57 strains in pretreatment to clarithromycin, metronidazole, and
      amoxicillin. RESULTS: Prior to second-line H. pylori eradication, the rate of
      resistance to clarithromycin was high at 84% (48/57). Similarly, resistance to
      metronidazole was low at 5.3% (3/57); however, no amoxicillin-resistant strains
      were found. The eradication rates for both lansoprazole and famotidine treatment
      groups were high at 97% (29/30) and 94% (29/31), respectively. CONCLUSIONS:
      Famotidine treatment including metronidazole-amoxicillin as second-line therapy
      provided a high eradication rate similar to lansoprazole therapy. Famotidine is
      therefore expected to serve as a useful H. pylori eradication regimen in patients
      with proton pump inhibitor allergy, an economic benefit in terms of reduced
      health-care costs is also anticipated.

PMID- 16961806
TI  - Prevalence and mechanisms of resistance to fluoroquinolones in Helicobacter
      pylori strains from patients living in Belgium.
AB  - BACKGROUND: Because of the increasing resistance of Helicobacter pylori against
      metronidazole and clarithromycin, alternative regimens including newer
      fluoroquinolones have been developed. We aimed to assess the prevalence as well
      as the mechanisms of this resistance in clinical isolates originating from
      patients living in Belgium. METHODS: Minimal inhibitory concentration (MIC)
      values of ciprofloxacin, levofloxacin, and moxifloxacin were determined by Etest
      method on 488 H. pylori isolates originating from patients who underwent upper
      gastrointestinal endoscopy at 10 different centers. Resistant strains (MIC values
      > 1 microg/ml) were evaluated for the presence of point mutations in the
      quinolone resistance-determining region (QRDR) of the gyrA by amplification and
      nucleotide sequence. RESULTS: Eighty-two (16.8%) of the strains were found
      resistant to all fluoroquinolones and 70 of these were further analyzed.
      Homogeneous and heterogeneous resistance were observed in 55 (78.6%) and in 15
      (21.4%) of the strains, respectively. QRDR sequencing revealed various mutations
      of the codons corresponding to Asn-87 and Asp-91 in all isolates with homogeneous
      resistance. However, in 12 of 15 strains displaying heterogenous resistance,
      mutations were only detected after subcultures of isolated colonies growing
      within the ellipse inhibition zone of the E-test. Amino acid substitutions in the
      QRDR of GyrA could not be directly related with the MIC values of the isolates.
      Fluoroquinolone-resistant mutants were easily selected in vitro at frequencies
      ranging between 10(-6) and 10(-7). Such selected mutants stably persisted after
      several serial passage in antibiotic-free agar. CONCLUSIONS: These results
      suggest that H. pylori resistance to fluoroquinolones is occurring at a high
      frequency in the Belgian population and that it is essentially mediated through a
      variety of point mutations occurring in a few loci of GyrA. As a consequence, we
      strongly suggest to determine the susceptibility of the infecting isolates to
      fluoroquinolones before administration of an anti-H. pylori regimen including
      these agents.

PMID- 16961807
TI  - Acute symptomatic gastritis due to Helicobacter heilmannii.
AB  - Helicobacter heilmannii is a Gram-negative spiral-shaped organism predominantly
      associated with zoonotic infection. Human pathology has also been described, but
      acute symptoms with complete resolution have been infrequently reported. We
      present a 50-year-old man in whom H. heilmannii gastritis presented as an acute
      febrile illness and was successfully treated with antibiotics and proton pump
      inhibitor. Epidemiology, diagnosis, and treatment of similar cases are reviewed.

PMID- 16961808
TI  - Helicobacter pylori infection and CagA protein translocation in human primary
      gastric epithelial cell culture.
AB  - BACKGROUND: Increasing evidence has shown that Helicobacter pylori CagA protein
      translocation into gastric epithelial cells plays an important role in the
      development of gastric inflammation and malignancy. Translocated CagA undergoes
      tyrosine phosphorylation in gastric adenocarcinoma cell line cells, and CagA
      involves disruption of cellular apical-junction complex in Madin-Darby canine
      kidney cells. METHODS: To elucidate whether these events take place in normal
      human gastric epithelium, we infected human primary gastric epithelial cells with
      H. pylori. RESULTS: Our results demonstrate that CagA protein was translocated
      into primary gastric epithelial cells and tyrosine phosphorylated. The
      translocated CagA induces cytoskeletal rearrangement and the disruption of tight
      junctions in primary gastric epithelial cells. CONCLUSIONS: This study provides
      direct evidence of the modulation of gastric epithelial cells by CagA protein
      translocation, and advances our understanding of the pathogenesis of H. pylori
      infection.

PMID- 16961809
TI  - Urea, fluorofamide, and omeprazole treatments alter helicobacter colonization in
      the mouse gastric mucosa.
AB  - BACKGROUND: Helicobacter pylori is a causative agent of gastric and duodenal
      ulcers and gastric cancer. Its urease enzyme allows survival in acid conditions
      and drives bacterial intracellular metabolism. We aimed to investigate the role
      of urease in determining the intragastric distribution of Helicobacter species in
      vivo. MATERIALS AND METHODS: The C57BL/6 mouse model of gastritis was used for
      infection with Helicobacter felis (CS1) or H. pylori (SS1). Urease-modulating
      compounds urea and/or fluorofamide (urease inhibitor) were administered to mice
      over 7 days. Concurrent gastric acid inhibition by omeprazole was also examined.
      Bacterial distribution in the antrum, body, antrum/body, and body/cardia
      transitional zones was graded "blindly" by histologic evaluation. Bacterial
      colony counts on corresponding tissue were also conducted. RESULTS: Urease
      inhibition by fluorofamide decreased H. pylori survival in most gastric regions
      (p < .05); however, there were no marked changes to H. felis colonization after
      this treatment. There was a consistent trend for decreased antral colonization,
      and an increase in antrum/body transitional zone and body colonization with
      excess 5% or 6% (w/v) urea treatment. Significant reductions of both Helicobacter
      species were observed with the co-treatment of urea and fluorofamide (p < .05).
      Collateral treatment with omeprazole did not alter H. pylori colonization
      patterns caused by urea/fluorofamide. CONCLUSIONS: Urease perturbations affect
      colonization patterns of Helicobacter species. Combined urea and fluorofamide
      treatment reduced the density of both Helicobacter species in our infection
      model.

PMID- 16961810
TI  - Apoptosis in Helicobacter pylori gastritis is related to cagA status.
AB  - BACKGROUND: Helicobacter pylori infection increases gastric epithelial cell
      apoptosis; however, the influence of cagA status is still controversial. We aimed
      to investigate if cagA status is related to apoptosis in H. pylori gastritis at
      different anatomic sites of the gastric mucosa. MATERIALS AND METHODS: We studied
      by immunohistochemistry (streptavidin-biotin method) pro-apoptotic (Bax and Bak)
      and antiapoptotic (Bcl-2 and Bcl-x) proteins expression, scored from 0 to 4, in
      gastric biopsies, at the antrum (lesser and greater curvatures), incisura, and
      corpus (greater curvature) from 50 patients with H. pylori gastritis (22 males,
      28 females, median age 40 years) and eight non-infected patients (6 males, median
      age 39.6 years). H. pylori and cagA status were determined by polymerase chain
      reaction. RESULTS: Apoptotic proteins were expressed in a granular pattern, in
      the cytoplasm of foveolar cells; Bax and Bak expression was higher than Bcl-2 and
      Bcl-x in most cases and was significantly higher in patients infected by cagA
      positive strains than in those infected by cagA-negative strains (p = .001). Bak
      expression was higher at the lesser curvature (antrum and incisura) than in the
      other regions (p = .002) and was correlated with atrophy. Anti-apoptotic proteins
      were significantly more expressed at the antral lesser curvature than in the
      other regions of the stomach (Bcl-2: p = .02; Bcl-x: p < .001). CONCLUSIONS:
      Infection with cagA-positive strains is significantly associated with
      overexpression of pro-apoptotic proteins in the gastric mucosa, mainly at the
      antral lesser curvature, which may have a role on atrophy development. Anti
      apoptotic proteins were also overexpressed at the lesser curvature, which may
      occur to keep epithelial cell turnover or might be related to malignant
      transformation.

PMID- 16961811
TI  - In vitro and in vivo complementation of the Helicobacter pylori arginase mutant
      using an intergenic chromosomal site.
AB  - BACKGROUND: Gene complementation strategies are important in validating the roles
      of genes in specific phenotypes. Complementation systems in Helicobacter pylori
      include shuttle vectors, which transform H. pylori at relatively low frequencies,
      and chromosomally based approaches. Chromosomal complementation strategies are
      susceptible to polar effects and disruption of other H. pylori genes, leading to
      unwanted pleiotropic effects. MATERIALS AND METHODS: A new complementation
      strategy was developed for H. pylori by utilizing a suicide plasmid vector that
      contains fragments of an H. pylori intergenic region (hp0203-hp0204), a
      chloramphenicol acetyltransferase cassette (cat), and a multiple-cloning site.
      Genes of interest could be cloned into the intergenic plasmid and the genes
      integrated into H. pylori by homologous recombination into the intergenic
      chromosomal region without disrupting any annotated H. pylori gene. The
      complementation system was validated using the gene encoding arginase (rocF).
      RESULTS: A rocF mutant unable to hydrolyze or consume l-arginine regained these
      functions by complementation with the wild-type rocF gene. Complemented strains
      also had restored arginase protein as determined by Western blot analysis. The
      complementation system could be successfully applied to multiple H. pylori
      strains. The intergenic region varied in length and sequence across 17 H. pylori
      strains, but the flanking-3' ends of the hp0203 and hp0204 coding regions were
      highly conserved. Inserting a cat cassette and wild-type rocF into the intergenic
      region did not alter the ability of strain SS1 to colonize mice. CONCLUSIONS:
      This complementation strategy should greatly facilitate genetic experiments in H.
      pylori.

PMID- 16961812
TI  - Deficiency in OGG1 protects against inflammation and mutagenic effects associated
      with H. pylori infection in mouse.
AB  - BACKGROUND: Helicobacter pylori infection is associated with gastric cancer.
      Study with the Big Blue mouse model has reported a mutagenic effect associated
      with the H. pylori infection, as a result in part of oxidative DNA damage. The
      present work investigates the consequences of a deficiency in the OGG1 DNA
      glycosylase, responsible for the excision of 8-oxo guanine, on the inflammatory
      and genotoxic host response to the infection. MATERIALS AND METHODS: Big Blue
      Ogg1-/- C57BL/6 mice were orally inoculated with H. pylori strain SS1 or vehicle
      only, and sacrificed after 1, 3, or 6 months. The serologic response, histologic
      lesions, mutant frequency, and spectra of mutations were assessed in the stomach
      and compared to what observed in the wild-type (Wt) context. RESULTS:
      Inflammatory lesions induced in the gastric mucosa of H. pylori-infected mice,
      corresponding to a moderate gastritis, were less severe in Ogg1-/- than in Wt Big
      Blue mice. Analysis of antimicrobial humoral immunity exhibited a lower IgG2a
      serum level (Th1 response) after 6 months of infection in Ogg1-/- than in the Wt
      mice. In these conditions, the H. pylori-SS1 infection in the Ogg1-/- mice did
      not induce a mutagenic effect at the gastric epithelial cells level, either after
      3 or 6 months. CONCLUSIONS: The inactivation of the OGG1 DNA glycosylase in mouse
      leads to less severe inflammatory lesions and abolished the mutagenic effect at
      the gastric epithelial cells level, induced by the H. pylori infection. These
      data suggest for the OGG1deficiency a protective role against inflammation and
      genotoxicity associated to the H. pylori infection.

PMID- 16961813
TI  - Monoclonal gammopathy of undetermined significance and Russell body formation in
      Helicobacter pylori gastritis.
AB  - BACKGROUND: Infection by Helicobacter pylori has been linked to monoclonal
      gammopathy of undetermined significance (MGUS). MGUS is thought to develop due to
      chronic antigenic stimulation in people with a specific genetic predisposition.
      METHODS AND RESULTS: We describe a patient presenting with dyspepsia associated
      with H. pylori-related erosive gastritis. Histopathologic findings revealed
      infiltration with plasma cells containing accumulated condensed intercisternal
      immunoglobulins, the so-called 'Russell bodies'. In addition, MGUS was present
      with total immunoglobulins within the normal range but a significantly decreased
      serum concentration of IgG subtype 3. Molecular analyses demonstrated IgH
      formation, T-cell receptor gamma rearrangement, and alterations within the IgHG3
      gene sequence. Following H. pylori eradication, gastritis and dyspepsia gradually
      resolved but MGUS persisted for at least 22 months. CONCLUSIONS: This is the
      first report to demonstrate that upon infection with H. pylori, an impaired
      secretory capacity of plasma cells due to specific molecular changes can present
      as Russell body gastritis. The molecular findings question a pathogenetic link
      between Russell bodies and H. pylori, but suggest genetic alterations in the
      immunoglobulin locus as the possible cause for both MGUS and Russell body
      gastritis.

PMID- 16961814
TI  - A review of autoimmune skin diseases in domestic animals: I - superficial
      pemphigus.
AB  - In humans, the pemphigus denomination encompasses a group of autoimmune
      blistering skin diseases with intraepidermal separation resulting from cell-cell
      detachment by acantholysis. Entities are classified based on the level of
      blistering in the epidermis, and both superficial (pemphigus foliaceus, IgA
      pemphigus) and deep (pemphigus vulgaris, pemphigus vegetans and paraneoplastic
      pemphigus) variants are recognized. In domestic animals, subsets of pemphigus
      have been recognized since the mid-1970s, and the disease classification
      resembles that used for human patients. This article reviews up-to-date knowledge
      on the epidemiology, clinical signs, histopathology, immunopathology and
      treatment outcome of superficial pemphigus in domestic animals. Detailed
      information on canine, feline, equine and caprine pemphigus foliaceus, canine and
      feline pemphigus erythematosus and canine panepidermal pustular pemphigus is
      provided.

PMID- 16961815
TI  - Studies on the role of routes of allergen exposure in high IgE-producing beagle
      dogs sensitized to house dust mites.
AB  - The current study aimed to investigate the role played by oral, epicutaneous, and
      inhalation routes of exposure to house dust mites (HDM). The colony of high IgE
      producing beagle dogs has been shown to develop pruritic dermatitis compatible
      with atopic dermatitis following environmental exposure (EE) to HDM. In crossover
      experiments, the response to EE was compared to two modified challenges, oral
      exposure (OE) and snood and muzzle exposure (SME). For OE, HDM were fed daily for
      3 days. For SME, ingestion of allergen was prevented but there was inhalation and
      epicutaneous exposure to all body regions except to one ear. In all experiments,
      dogs were challenged for three consecutive days, and evaluated before, 6 h after
      exposure and daily thereafter, for 5 days. After a wash-out period, groups were
      crossed-over so that each dog was randomly challenged to all three protocols.
      Clinical scores were analysed using least squares analysis of variance. All dogs
      developed pruritic dermatitis regardless of the protocol. With OE, lesions
      developed in the same body regions as with EE although scores were lower. This
      difference became more evident after the first 3 days when OE scores decreased
      and EE scores continued to increase. The scores of covered and uncovered ears did
      not differ with SME. Scores for the remainder of the body were significantly
      lower than for EE. The development of lesions on covered ears supports the
      importance of inhalation or a systemic reaction to epicutaneous exposure in other
      areas. It is concluded that all routes are important and have additive effects,
      that route of exposure does not determine the distribution of lesions and that
      continuous epicutaneous exposure probably plays the most important role.

PMID- 16961816
TI  - Evaluation of Th1-like, Th2-like and immunomodulatory cytokine mRNA expression in
      the skin of dogs with immunomodulatory-responsive lymphocytic-plasmacytic
      pododermatitis.
AB  - The term immunomodulatory-responsive lymphocytic-plasmacytic pododermatitis (ImR
      LPP) has previously been proposed to denote a subpopulation of dogs with
      idiopathic pododermatitis. The objective of this study was to quantify the
      expression of mRNA encoding Th(1)-like [interferon (IFN)-gamma, interleukin (IL)
      2 and IL-12], Th(2)-like [IL-4 and IL-6] and immunomodulatory cytokines [IL-10
      and transforming growth factor (TGF)-beta] in lesional ImR-LPP, nonlesional ImR
      LPP and healthy control pedal skin. Gene transcripts were quantified using TaqMan
      real-time reverse transcriptase-polymerase chain reaction assays. The skin of
      dogs with ImR-LPP had significant overexpression of IL-6 mRNA (P < 0.05) and
      significant underexpression of IL-12 mRNA (P < 0.01) compared to healthy
      controls. In addition, lesional ImR-LPP skin had significantly higher levels of
      IL-10 transcripts compared to healthy control pedal skin (P < 0.05). Although not
      attaining significance (P = 0.07), a trend towards reduced TGF-beta mRNA
      expression in lesional ImR-LPP skin was also evident. There were no significant
      differences in the levels of IFN-gamma or IL-2 mRNA transcripts among the three
      skin sample sources. IL-4 mRNA was detected in only one lesional sample. These
      results suggest that the pathogenesis of ImR-LPP may be associated with a T-cell
      mediated inflammatory response characterized by impaired Th(1)-like, but enhanced
      Th(2)-like cytokine expression.

PMID- 16961817
TI  - Rapid detection of Arthroderma vanbreuseghemii in rabbit skin specimens by PCR
      RFLP.
AB  - Three commercial rabbit farms independently reported suspected dermatophyte
      infections during 2004. Cultures confirmed that the infection was caused by the
      zoophilic Tricophyton mentagrophytes, while mating studies and sequencing of the
      internal transcribed spacer (ITS)1/4 polymerase chain reaction products, directly
      amplified from skin lesions and from pure culture isolates, established its
      Arthroderma vanbreuseghemii lineage. Subsequently, the corresponding DdeI
      restriction profiles of the ITS1/4 PCR products matched one of the two published
      T. mentagrophytes complex profiles. Sequence analysis of the published ITS
      sequences predicted distinct DdeI restriction sites for Arthroderma benhamiae and
      A. vanbreuseghemii, while all DdeI-generated restriction fragment length
      polymorphisms of the rabbit isolates were identical to those of A.
      vanbreuseghemii. The proposed procedure can be used for rapid dermatophyte
      detection and presumptive T. mentagrophytes identification.

PMID- 16961818
TI  - Isolation of Microsporum canis from the hair coat of pet dogs and cats belonging
      to owners diagnosed with M. canis tinea corporis.
AB  - Microsporum canis has been frequently isolated from human cases of tinea capitis
      and tinea corporis. The infection may be acquired from infected animals with
      cutaneous lesions but also from asymptomatic carriers or from the environment. As
      asymptomatic M. canis carriers are considered to be a critical factor in the
      epidemiology of dermatophytosis in humans, this study investigated the
      relationship between the presence of dermatophytes on the hair coats of dogs and
      cats without cutaneous lesions and the occurrence of the disease in their
      respective owners. A total of 136 dogs and 248 cats were sampled from January
      1999 to January 2005. Seventy-eight animals (22 dogs and 56 cats) belonged to
      individuals affected by tinea corporis caused by M. canis and 306 (114 dogs and
      192 cats) to individuals without dermatophytosis. Age, sex, breed, habitat and
      season were recorded for each animal and examined as potential risk factors.
      Dermatophytes were isolated from 20.5% of the dogs and 28.2% of the cats.
      Microsporum canis was isolated from 36.4% of dogs cohabiting with owners
      diagnosed with tinea corporis but it was never isolated from dogs whose owners
      had no lesions. By contrast, M. canis was isolated from 53.6% of cats cohabiting
      with owners diagnosed with tinea corporis and from 14.6% of cats whose owners had
      no signs of the disease. These results clearly indicate that both cats and dogs
      should be considered as a major source of pathogenic dermatophytes for humans
      even when they do not present clinical signs of dermatophytosis.

PMID- 16961819
TI  - Screening of Staphylococcus aureus, Staphylococcus intermedius, and
      Staphylococcus schleiferi isolates obtained from small companion animals for
      antimicrobial resistance: a retrospective review of 749 isolates (2003-04).
AB  - Companion animal staphylococcal isolate antibiograms were screened
      retrospectively to determine the frequency of methicillin-resistant (MR)
      infection by Staphylococcus aureus, Staphylococcus intermedius, and
      Staphylococcus schleiferi. Rates of MR were: S. aureus 35%, S. intermedius 17%,
      and S. schleiferi 40%. Frequency of isolation of methicillin-resistant S. aureus
      (MRSA) from dogs and cats was similar, whereas methicillin-resistant S.
      intermedius (MRSI) and methicillin-resistant S. schleiferi (MRSS) were
      significantly more common in dogs. MRSS was more commonly associated with
      superficial (skin and ear canal) infections, whereas MRSA was more commonly
      associated with deep infections. The MR strain resistance pattern to other
      classes of antibiotics was also investigated. MRSA was resistant to the most
      classes of antibiotics, followed by MRSI, while MRSS maintained the most
      favourable susceptibility profile. MR staphylococci may pose a significant risk
      to animal and public health. Therefore, to avoid selecting for resistant strains
      in cases of suspected staphylococcal infection, clinicians should consider
      culture and susceptibility testing early in the course of treatment.

PMID- 16961820
TI  - Comparison of clinical history and dermatologic findings in 29 dogs with severe
      eosinophilic dermatitis: a retrospective analysis.
AB  - The medical records and histopathological sections of 29 dogs diagnosed with a
      unique eosinophilic dermatitis resembling Wells' syndrome were reviewed in an
      attempt to elucidate the pathogenesis of this syndrome. The medical records were
      reviewed for information on dermatological lesion appearance, systemic signs in
      other organ systems, clinical analyte abnormalities, and drug therapy.
      Histological sections of dogs with moderate to severe eosinophilic dermatitis
      without folliculitis and furunculosis were reviewed and evaluated for the
      presence of collagen flame figures. Three categories of patients were found.
      Category 1 consisted of 17 dogs treated for vomiting and/or diarrhoea (often
      haematochezia or haematemesis) prior (mean: 4.6 days) to the onset of skin
      lesions. Fourteen category 1 dogs had erythematous lesions (macules, papules or
      plaques) that were most pronounced on the abdomen. Sixteen of the 17 dogs
      received multiple classes of drugs, and 59% were hypoalbuminemic. Category 2
      consisted of five dogs that had skin lesions and gastrointestinal signs at
      presentation and four of these dogs were hypoalbuminemic. Category 3 included
      seven dogs without enteric illness. A positive drug score was found in six
      category 1 dogs and one each from categories 2 and 3. Eighteen cases had
      eosinophilic dermatitis without flame figures, seven cases had early flame
      figures and four had well-developed flame figures. These changes did not
      correlate with the categories of clinical presentation. More than 50% of the dogs
      developed eosinophilic dermatitis following treatment for severe gastrointestinal
      disease. The authors propose that this represents a unique syndrome that may have
      causal drug association.

PMID- 16961821
TI  - Objective measurement of pruritus in dogs: a preliminary study using activity
      monitors.
AB  - Pruritus is an important clinical sign and quality-of-life measure in canine
      dermatology, but can be difficult to assess objectively. Several studies in
      humans have used activity monitors to measure nocturnal scratching in patients
      with atopic dermatitis. The results correlate with observation of scratching,
      scoring in atopic dermatitis indices and levels of inflammatory chemokines. The
      aim of this study was to examine whether an activity monitor could be used to
      detect elevated interexercise (i.e. 'resting') activity in atopic dogs compared
      to healthy dogs. Five healthy dogs and six dogs with atopic dermatitis were
      fitted with a collar-mounted activity monitor (Actiwatch) that recorded the piezo
      electric voltage generated over 15-s epochs for 7 days. Data from defined periods
      of exercise, playing, etc., were disregarded. Within each group, median (+/-
      interquartile range) epoch activity was similar during the day (atopic 21.0 [9.8
      24.8]; healthy 5.1 [4.6-6.0]) and evening (atopic 19.1 [10.9-25.2]; healthy 5.8
      [5.3-11.7]), and significantly lower overnight (atopic 5.8 [4.1-15.7]; healthy
      2.5 [1.6-4.4]) (Mann-Whitney test; P < 0.05). The mean epoch activity, however,
      was significantly higher in atopic dogs compared to healthy dogs for all three
      time periods (P < 0.05). This study provides preliminary evidence that activity
      monitors could objectively assess canine pruritus in the normal home environment.

PMID- 16961823
TI  - Proceedings of the 10th International Congress of the European Association for
      Veterinary Pharmacology and Toxicology (EAVPT), Turin, Italy, 17-22 September
      2006.

PMID- 16961916
TI  - Synchronous mucinous adenocarcinoma of the rectosigmoid seeding onto a pre
      existing anal fistula.
AB  - Carcinoma within a long-standing fistula-in-ano is rare and may be defined by
      specific neoplastic involvement of the fistulous track in the absence of rectal
      mucosal carcinoma. The presence of a carcinoma of mucinous histology occurring
      synchronously in the perianal region and the colon is exceptionally rare. We
      present a case with a review of the literature concerning its aetiopathogenesis
      and treatment. A 72-year-old man with a 2 months history of dark red rectal
      bleeding and mucus per rectum with alternating constipation and diarrhoea, was
      observed. Clinical examination and a barium enema showed a perianal fistula and
      an annular stenosing lesion of the rectosigmoid. Preoperative CT scan confirmed
      the colonic lesion. Colonic resection and wide fistula excision were performed.
      Histology showed an adenocarcinoma with a clear resection margins. The fistula
      also showed a similar histology. Chemoradiation (5-Fluorouracil (425 mg/m2) and
      Leucovorin (20 mg/m2) with 4500 cGy external beam radiotherapy was utilized.
      Subsequent clinical follow-up and CT examination of the patient has not revealed
      recurrent disease at 14 months.

PMID- 16961917
TI  - Arch vessel injury: geometrical considerations. Implications for the mechanism of
      traumatic myocardial infarction II.
AB  - BACKGROUND: Various types of vascular injury have been reported in the medical
      literature; the isthmic part of the aorta is at particularly high risk of
      traumatic rupture. Early diagnosis results in better survival, justifying the
      search for potential risk factors and diagnostic tests. The aim of this research
      was to investigate the complex mechanism of blunt injury to the vascular wall
      with particular focus on the branching region of the vessels. Geometric
      peculiarities were investigated. METHODS: Multi-phase equations have been used.
      The system of equations with certain boundary conditions was solved numerically
      by applying the finite-difference method with order of approximation equal to
      0.0001. RESULTS: The degree of curvature (the Dean number) is highly informative
      about the shear stress on the external surface of the vessel. An important
      function of the blood flow on the external wall is to destroy rouleaux. The
      viscosity of phase 2 (f2) exceeds, by many times, the viscosity of phase 1 (f1).
      The major stress created by blood flow is expressed as the shear stress of f2.
      The volume fraction of rouleaux depends to a greater degree on the concentration
      of erythrocytes (expressed as the viscosity of the mixture) than on the shear
      stress. The peculiarities of rouleaux formation were assessed and their impact on
      the local shear stress and, therefore, on the internal wall was determined in
      relation to the erythrocyte concentration. CONCLUSION: The results of this
      research take into account certain geometrical peculiarities of the branching
      part of the vessel. The mathematical model created in this study will improve our
      understanding of the complex mechanism of blunt injury to the vascular wall and,
      therefore, conditions such as aortic rupture and traumatic acute myocardial
      infarction.

PMID- 16961918
TI  - Short-term arginine deprivation results in large-scale modulation of hepatic gene
      expression in both normal and tumor cells: microarray bioinformatic analysis.
AB  - BACKGROUND: We have reported arginine-sensitive regulation of LAT1 amino acid
      transporter (SLC 7A5) in normal rodent hepatic cells with loss of arginine
      sensitivity and high level constitutive expression in tumor cells. We
      hypothesized that liver cell gene expression is highly sensitive to alterations
      in the amino acid microenvironment and that tumor cells may differ substantially
      in gene sets sensitive to amino acid availability. To assess the potential number
      and classes of hepatic genes sensitive to arginine availability at the RNA level
      and compare these between normal and tumor cells, we used an Affymetrix
      microarray approach, a paired in vitro model of normal rat hepatic cells and a
      tumorigenic derivative with triplicate independent replicates. Cells were exposed
      to arginine-deficient or control conditions for 18 hours in medium formulated to
      maintain differentiated function. RESULTS: Initial two-way analysis with a p
      value of 0.05 identified 1419 genes in normal cells versus 2175 in tumor cells
      whose expression was altered in arginine-deficient conditions relative to
      controls, representing 9-14% of the rat genome. More stringent bioinformatic
      analysis with 9-way comparisons and a minimum of 2-fold variation narrowed this
      set to 56 arginine-responsive genes in normal liver cells and 162 in tumor cells.
      Approximately half the arginine-responsive genes in normal cells overlap with
      those in tumor cells. Of these, the majority was increased in expression and
      included multiple growth, survival, and stress-related genes. GADD45, TA1/LAT1,
      and caspases 11 and 12 were among this group. Previously known amino acid
      regulated genes were among the pool in both cell types. Available cDNA probes
      allowed independent validation of microarray data for multiple genes. Among genes
      downregulated under arginine-deficient conditions were multiple genes involved in
      cholesterol and fatty acid metabolism. Expression of low-density lipoprotein
      receptor was decreased in both normal and tumor cells. CONCLUSION: Arginine
      sensitive regulation appears to be an important homeostatic mechanism to
      coordinate cell response and nutrient availability in hepatic cells. Genes
      predicted as arginine-responsive in stringent microarray data analysis were
      confirmed by Northern blot and RT-PCR. Although the profile of arginine
      responsive genes is altered and increased, a considerable portion of the
      "arginome" is maintained upon neoplastic transformation.

PMID- 16961919
TI  - Scanning sequences after Gibbs sampling to find multiple occurrences of
      functional elements.
AB  - BACKGROUND: Many DNA regulatory elements occur as multiple instances within a
      target promoter. Gibbs sampling programs for finding DNA regulatory elements de
      novo can be prohibitively slow in locating all instances of such an element in a
      sequence set. RESULTS: We describe an improvement to the A-GLAM computer program,
      which predicts regulatory elements within DNA sequences with Gibbs sampling. The
      improvement adds an optional "scanning step" after Gibbs sampling. Gibbs sampling
      produces a position specific scoring matrix (PSSM). The new scanning step
      resembles an iterative PSI-BLAST search based on the PSSM. First, it assigns an
      "individual score" to each subsequence of appropriate length within the input
      sequences using the initial PSSM. Second, it computes an E-value from each
      individual score, to assess the agreement between the corresponding subsequence
      and the PSSM. Third, it permits subsequences with E-values falling below a
      threshold to contribute to the underlying PSSM, which is then updated using the
      Bayesian calculus. A-GLAM iterates its scanning step to convergence, at which
      point no new subsequences contribute to the PSSM. After convergence, A-GLAM
      reports predicted regulatory elements within each sequence in order of increasing
      E-values, so users have a statistical evaluation of the predicted elements in a
      convenient presentation. Thus, although the Gibbs sampling step in A-GLAM finds
      at most one regulatory element per input sequence, the scanning step can now
      rapidly locate further instances of the element in each sequence. CONCLUSION:
      Datasets from experiments determining the binding sites of transcription factors
      were used to evaluate the improvement to A-GLAM. Typically, the datasets included
      several sequences containing multiple instances of a regulatory motif. The
      improvements to A-GLAM permitted it to predict the multiple instances.

PMID- 16961920
TI  - The pathogenesis of HIV infection: stupid may not be so dumb after all.
AB  - In the mid-1990's, researchers hypothesized, based on new viral load data, that
      HIV-1 causes CD4+ T-cell depletion by direct cytopathic effect. New data from non
      human primate studies has raised doubts about this model of HIV-1 pathogenesis.
      Despite having high levels of viremia, most SIV infections are well tolerated by
      their natural hosts. Two recent studies of these models provide information,
      which may be useful in determining how HIV-1 causes CD4+ T-cell loss. A full
      understanding of pathogenesis may lead to novel therapies, which preserve the
      immune system without blocking virus replication.

PMID- 16961921
TI  - AgBase: a functional genomics resource for agriculture.
AB  - BACKGROUND: Many agricultural species and their pathogens have sequenced genomes
      and more are in progress. Agricultural species provide food, fiber,
      xenotransplant tissues, biopharmaceuticals and biomedical models. Moreover, many
      agricultural microorganisms are human zoonoses. However, systems biology from
      functional genomics data is hindered in agricultural species because agricultural
      genome sequences have relatively poor structural and functional annotation and
      agricultural research communities are smaller with limited funding compared to
      many model organism communities. DESCRIPTION: To facilitate systems biology in
      these traditionally agricultural species we have established "AgBase", a curated,
      web-accessible, public resource http://www.agbase.msstate.edu for structural and
      functional annotation of agricultural genomes. The AgBase database includes a
      suite of computational tools to use GO annotations. We use standardized
      nomenclature following the Human Genome Organization Gene Nomenclature guidelines
      and are currently functionally annotating chicken, cow and sheep gene products
      using the Gene Ontology (GO). The computational tools we have developed accept
      and batch process data derived from different public databases (with different
      accession codes), return all existing GO annotations, provide a list of products
      without GO annotation, identify potential orthologs, model functional genomics
      data using GO and assist proteomics analysis of ESTs and EST assemblies. Our
      journal database helps prevent redundant manual GO curation. We encourage and
      publicly acknowledge GO annotations from researchers and provide a service for
      researchers interested in GO and analysis of functional genomics data.
      CONCLUSION: The AgBase database is the first database dedicated to functional
      genomics and systems biology analysis for agriculturally important species and
      their pathogens. We use experimental data to improve structural annotation of
      genomes and to functionally characterize gene products. AgBase is also directly
      relevant for researchers in fields as diverse as agricultural production, cancer
      biology, biopharmaceuticals, human health and evolutionary biology. Moreover, the
      experimental methods and bioinformatics tools we provide are widely applicable to
      many other species including model organisms.

PMID- 16961922
TI  - Severe osteomyelitis caused by Myceliophthora thermophila after a pitchfork
      injury.
AB  - BACKGROUND: Traumatic injuries occurring in agricultural settings are often
      associated with infections caused by unusual organisms. Such agents may be
      difficult to isolate, identify, and treat effectively. CASE REPORT: A 4-year-old
      boy developed an extensive infection of his knee and distal femur following a
      barnyard pitchfork injury. Ultimately the primary infecting agent was determined
      to be Myceliophthora thermophila, a thermophilic melanized hyphomycete, rarely
      associated with human infection, found in animal excreta. Because of resistance
      to standard antifungal agents including amphotericin B and caspofungin, therapy
      was instituted with a prolonged course of terbinafine and voriconazole.
      Voriconazole blood levels demonstrated that the patient required a drug dosage
      (13.4 mg/kg) several fold greater than that recommended for adults in order to
      attain therapeutic blood levels. CONCLUSION: Unusual pathogens should be sought
      following traumatic farm injuries. Pharmacokinetic studies may be of critical
      importance when utilizing antifungal therapy with agents for which little
      information exists regarding drug metabolism in children.

PMID- 16961923
TI  - Global gene expression during stringent response in Corynebacterium glutamicum in
      presence and absence of the rel gene encoding (p)ppGpp synthase.
AB  - BACKGROUND: The stringent response is the initial reaction of microorganisms to
      nutritional stress. During stringent response the small nucleotides (p)ppGpp act
      as global regulators and reprogram bacterial transcription. In this work, the
      genetic network controlled by the stringent response was characterized in the
      amino acid-producing Corynebacterium glutamicum. RESULTS: The transcriptome of a
      C. glutamicum rel gene deletion mutant, unable to synthesize (p)ppGpp and to
      induce the stringent response, was compared with that of its rel-proficient
      parent strain by microarray analysis. A total of 357 genes were found to be
      transcribed differentially in the rel-deficient mutant strain. In a second
      experiment, the stringent response was induced by addition of DL-serine
      hydroxamate (SHX) in early exponential growth phase. The time point of the
      maximal effect on transcription was determined by real-time RT-PCR using the
      histidine and serine biosynthetic genes. Transcription of all of these genes
      reached a maximum at 10 minutes after SHX addition. Microarray experiments were
      performed comparing the transcriptomes of SHX-induced cultures of the rel
      proficient strain and the rel mutant. The differentially expressed genes were
      grouped into three classes. Class A comprises genes which are differentially
      regulated only in the presence of an intact rel gene. This class includes the non
      essential sigma factor gene sigB which was upregulated and a large number of
      genes involved in nitrogen metabolism which were downregulated. Class B comprises
      genes which were differentially regulated in response to SHX in both strains,
      independent of the rel gene. A large number of genes encoding ribosomal proteins
      fall into this class, all being downregulated. Class C comprises genes which were
      differentially regulated in response to SHX only in the rel mutant. This class
      includes genes encoding putative stress proteins and global transcriptional
      regulators that might be responsible for the complex transcriptional patterns
      detected in the rel mutant when compared directly with its rel-proficient parent
      strain. CONCLUSION: In C. glutamicum the stringent response enfolds a fast answer
      to an induced amino acid starvation on the transcriptome level. It also showed
      some significant differences to the transcriptional reactions occurring in
      Escherichia coli and Bacillus subtilis. Notable are the rel-dependent regulation
      of the nitrogen metabolism genes and the rel-independent regulation of the genes
      encoding ribosomal proteins.

PMID- 16961924
TI  - High level expression of human epithelial beta-defensins (hBD-1, 2 and 3) in
      papillomavirus induced lesions.
AB  - BACKGROUND: Epithelial defensins including human beta-defensins (hBDs) and alpha
      defensins (HDs) are antimicrobial peptides that play important roles in the
      mucosal defense system. However, the role of defensins in papillomavirus induced
      epithelial lesions is unknown. RESULTS: Papilloma tissues were prospectively
      collected from 15 patients with recurrent respiratory papillomatosis (RRP) and
      analyzed for defensins and chemokine IL-8 expression by quantitative, reverse
      transcriptase polymerase chain reaction (RT-PCR) assays. HBD-1, -2 and -3 mRNAs
      were detectable in papilloma samples from all RRP patients and the levels were
      higher than in normal oral mucosal tissues from healthy individuals.
      Immunohistochemical analysis showed that both hBD-1 and 2 were localized in the
      upper epithelial layers of papilloma tissues. Expression of hBD-2 and hBD-3
      appeared to be correlated as indicated by scatter plot analysis (r = 0.837, p <
      0.01) suggesting that they were co-inducible in papillomavirus induced lesions.
      Unlike hBDs, only low levels of HD5 and HD6 were detectable in papillomas and in
      oral mucosa. CONCLUSION: Human beta-defensins are upregulated in respiratory
      papillomas. This novel finding suggests that hBDs might contribute to innate and
      adaptive immune responses targeted against papillomavirus-induced epithelial
      lesions.

PMID- 16961925
TI  - Diabetes alters vascular mechanotransduction: pressure-induced regulation of
      mitogen activated protein kinases in the rat inferior vena cava.
AB  - BACKGROUND: Diabetes mellitus is an important risk factor for increased vein
      graft failure after bypass surgery. However, the cellular and molecular
      mechanism(s) underlying vessel attrition in this population remain largely
      unexplored. Recent reports have suggested that the pathological remodeling of
      vein grafts may be mediated by mechanically-induced activation of the mitogen
      activated protein kinase (MAPK) signaling pathways and the MAPK-related induction
      of caspase-3 activity. On the basis of these findings, we hypothesized that
      diabetes may be associated with alterations in how veins "sense" and "respond" to
      altered mechanical loading. METHODS: Inferior venae cavae (IVC) from the non
      diabetic lean (LNZ) and the diabetic obese (OSXZ) Zucker rats were isolated and
      incubated ex vivo under basal or pressurized conditions (120 mmHg). Protein
      expression, basal activation and the ability of increased pressure to activate
      MAPK pathways and apoptosis-related signaling was evaluated by immunoblot
      analysis. RESULTS: Immunoblot analyses revealed differential expression and
      activation of extracellular signal-regulated kinase (ERK1/2), p38 and c-Jun NH2
      terminal kinase (JNK) MAPKs in the IVCs of diabetic rats as compared to non
      diabetic rats. In particular, the expression and basal phosphorylation of p38beta
      (52.3 +/- 11.8%; 45.8 +/- 18.2%), JNK 1- (21.5 +/- 9.3%; 19.4 +/- 11.6%) and
      JNK3-MAPK (16.8 +/- 3.3%; 29.5 +/- 17.6%) were significantly higher (P < 0.05) in
      the diabetic vena cava. An acute increase in IVC intraluminal pressure failed to
      increase the phosphorylation of ERK1-, JNK-2, or any of the p38-MAPKs in the
      diabetic obese Zucker rats. Also, IVC loading in the LNZ led to a 276.0 +/- 36.0%
      and 85.8 +/- 25.1% (P < 0.05) increase in the cleavage of caspase-3 and caspase
      9, respectively, with no effect on these molecules in the OSXZ. No differences
      were found in the regulation of Bax and Bcl-2 between groups. However, basal
      expression levels of Akt, phospho-Akt, PTEN, phospho-PTEN and phospho-Bad were
      higher in the diabetic venae cavae (P < 0.05). CONCLUSION: These data suggest
      that diabetes is associated with significant alteration in the ability of the
      vena cava to activate MAPK- and apoptosis-related signaling. Whether these
      changes are associated with the increased vein graft attrition seen in the
      diabetic population will require further investigation.

PMID- 16961927
TI  - Immunohistochemical analysis of an ectopic endometriosis in the uterine round
      ligament.
AB  - A rare case of the inguinal endometriosis was reported with immunohistochemical
      analysis. A 28-year-old woman had a thumb-sized tumor in the right groin for two
      years with a gradual increase in size and pain. An operation revealed an elastic
      hard tumor with an unclear margin and adhesion to the uterine round ligament. The
      histology showed irregular proliferation of the endometrial glands and stroma.
      The glandular epithelium stained weakly positive against CD125 antibody and the
      stromal matrix stained strongly positive against CD10 antibody. The nucleus in
      both the epithelial and stromal cells stained strongly positive against
      progesterone and estrogen receptor antibodies, and the cytoplasm in both types of
      cells stained moderately positive against COX-2 (cyclooxygenase-2) antibody. In
      conclusion, the combination of estrogen or progesterone receptor antibody for the
      nucleus and CD10 or COX-2 antibody for the cytoplasm could enhance the accuracy
      of diagnosis for ectopic endometriosis.

PMID- 16961926
TI  - Translocation and potential neurological effects of fine and ultrafine particles
      a critical update.
AB  - Particulate air pollution has been associated with respiratory and cardiovascular
      disease. Evidence for cardiovascular and neurodegenerative effects of ambient
      particles was reviewed as part of a workshop. The purpose of this critical update
      is to summarize the evidence presented for the mechanisms involved in the
      translocation of particles from the lung to other organs and to highlight the
      potential of particles to cause neurodegenerative effects. Fine and ultrafine
      particles, after deposition on the surfactant film at the air-liquid interface,
      are displaced by surface forces exerted on them by surfactant film and may then
      interact with primary target cells upon this displacement. Ultrafine and fine
      particles can then penetrate through the different tissue compartments of the
      lungs and eventually reach the capillaries and circulating cells or constituents,
      e.g. erythrocytes. These particles are then translocated by the circulation to
      other organs including the liver, the spleen, the kidneys, the heart and the
      brain, where they may be deposited. It remains to be shown by which mechanisms
      ultrafine particles penetrate through pulmonary tissue and enter capillaries. In
      addition to translocation of ultrafine particles through the tissue, fine and
      coarse particles may be phagocytized by macrophages and dendritic cells which may
      carry the particles to lymph nodes in the lung or to those closely associated
      with the lungs. There is the potential for neurodegenerative consequence of
      particle entry to the brain. Histological evidence of neurodegeneration has been
      reported in both canine and human brains exposed to high ambient PM levels,
      suggesting the potential for neurotoxic consequences of PM-CNS entry. PM mediated
      damage may be caused by the oxidative stress pathway. Thus, oxidative stress due
      to nutrition, age, genetics among others may increase the susceptibility for
      neurodegenerative diseases. The relationship between PM exposure and CNS
      degeneration can also be detected under controlled experimental conditions.
      Transgenic mice (Apo E -/-), known to have high base line levels of oxidative
      stress, were exposed by inhalation to well characterized, concentrated ambient
      air pollution. Morphometric analysis of the CNS indicated unequivocally that the
      brain is a critical target for PM exposure and implicated oxidative stress as a
      predisposing factor that links PM exposure and susceptibility to
      neurodegeneration. Together, these data present evidence for potential
      translocation of ambient particles on organs distant from the lung and the
      neurodegenerative consequences of exposure to air pollutants.

PMID- 16961928
TI  - Multiplatform genome-wide identification and modeling of functional human
      estrogen receptor binding sites.
AB  - BACKGROUND: Transcription factor binding sites (TFBS) impart specificity to
      cellular transcriptional responses and have largely been defined by consensus
      motifs derived from a handful of validated sites. The low specificity of the
      computational predictions of TFBSs has been attributed to ubiquity of the motifs
      and the relaxed sequence requirements for binding. We posited that the inadequacy
      is due to limited input of empirically verified sites, and demonstrated a
      multiplatform approach to constructing a robust model. RESULTS: Using the TFBS
      for the estrogen receptor (ER)alpha (estrogen response element [ERE]) as a model
      system, we extracted EREs from multiple molecular and genomic platforms whose
      binding to ERalpha has been experimentally confirmed or rejected. In silico
      analyses revealed significant sequence information flanking the standard binding
      consensus, discriminating ERE-like sequences that bind ERalpha from those that
      are nonbinders. We extended the ERE consensus by three bases, bearing a terminal
      G at the third position 3' and an initiator C at the third position 5', which
      were further validated using surface plasmon resonance spectroscopy. Our
      functional human ERE prediction algorithm (h-ERE) outperformed existing
      predictive algorithms and produced fewer than 5% false negatives upon
      experimental validation. CONCLUSION: Building upon a larger experimentally
      validated ERE set, the h-ERE algorithm is able to demarcate better the universe
      of ERE-like sequences that are potential ER binders. Only 14% of the predicted
      optimal binding sites were utilized under the experimental conditions employed,
      pointing to other selective criteria not related to EREs. Other factors, in
      addition to primary nucleotide sequence, will ultimately determine binding site
      selection.

PMID- 16961929
TI  - Family and home correlates of television viewing in 12-13 year old adolescents:
      the Nepean Study.
AB  - BACKGROUND: Few young people meet television viewing guidelines. PURPOSE: To
      determine the association between factors in the family and home environment and
      watching television, including videos and DVDs, in early adolescence. METHODS:
      Cross-sectional, self-report survey of 343 adolescents aged 12-13 years (173
      girls), and their parents (338 mothers, 293 fathers). Main measures were factors
      in the family and home environment potentially associated with adolescents
      spending >or= 2 hours per day in front of the television. Factors examined
      included family structure, opportunities to watch television/video/DVDs,
      perceptions of rules and regulations on television viewing, and television
      viewing practices. RESULTS: Two-thirds of adolescents watched >or= 2 hours
      television per day. Factors in the family and home environment associated with
      adolescents watching television >or= 2 hours per day include adolescents who have
      siblings (Adjusted Odds Ratio [95%CI] AOR = 3.0 [1.2, 7.8]); access to pay
      television (AOR = 2.0 [1.1, 3.7]); ate snacks while watching television (AOR =
      3.1 [1.8, 5.4]); co-viewed television with parents (AOR = 2.3 [1.3, 4.2]); and
      had mothers who watched >or= 2 hours television per day (AOR = 2.4 [1.3, 4.6]).
      CONCLUSION: There are factors in the family and home environment that influence
      the volume of television viewed by 12-13 year olds. Television plays a central
      role in the family environment, potentially providing a means of recreation among
      families of young adolescents for little cost. Interventions which target family
      television viewing practices and those of parents, in particular, are more likely
      to be effective than interventions which directly target adolescent viewing
      times.

PMID- 16961930
TI  - Somatic deletion of the NF1 gene in a neurofibromatosis type 1-associated
      malignant melanoma demonstrated by digital PCR.
AB  - BACKGROUND: Neurofibromatosis type 1 (NF1) is the most common hereditary
      neurocutaneous disorder and it is associated with an elevated risk for malignant
      tumors of tissues derived from neural crest cells. The NF1 gene is considered a
      tumor suppressor gene and inactivation of both copies can be found in NF1
      associated benign and malignant tumors. Melanocytes also derive from neural crest
      cells but melanoma incidence is not markedly elevated in NF1. In this study we
      could analyze a typical superficial spreading melanoma of a 15-year-old boy with
      NF1 for loss of heterozygosity (LOH) within the NF1 gene. Neurofibromatosis in
      this patient was transmitted by the boy's farther who carried the mutation NF1 c.
      5546 G/A. RESULTS: Melanoma cells were isolated from formalin-fixed tissue by
      liquid coverslip laser microdissection. In order to obtain statistically
      significant LOH data, digital PCR was performed at the intragenic microsatellite
      IVS27AC28 with DNA of approx. 3500 melanoma cells. Digital PCR detected 23
      paternal alleles and one maternal allele. Statistical analysis by SPRT confirmed
      significance of the maternal allele loss. CONCLUSION: To our knowledge, this is
      the first molecular evidence of inactivation of both copies of the NF1 gene in a
      typical superficial spreading melanoma of a patient with NF1. The classical
      double-hit inactivation of the NF1 gene suggests that the NF1 genetic background
      promoted melanoma genesis in this patient.

PMID- 16961931
TI  - Ritual plants of Muslim graveyards in northern Israel.
AB  - This article surveys the botanical composition of 40 Muslim graveyards in
      northern Israel, accompanied by an ethnobotanical study of the folkloristic
      traditions of the use of these plants in cemeteries. Three groups of plants were
      found to be repeated systematically and were also recognized for their ritual
      importance: aromatics herbs (especially Salvia fruticosa and Rosmarinus
      officinalis), white flowered plants (mainly Narcissus tazetta, Urginea maritima,
      Iris spp. and Pancratium spp.) and Cupressus sempervirens as the leading cemetery
      tree. As endemic use we can indicate the essential role of S. fruticosa as the
      main plant used in all human rites of passage symbolizing the human life cycle.
      The rosemary is of European origin while the use of basil is of Indian influence.
      The use of white flowers as cemeteries plants reflects an old European influence
      and almost the same species are used or their congeners. Most of the trees and
      shrubs that are planted in Muslim cemeteries in Israel have the same use in
      ancient as well in modern European cultures. In conclusion, our findings on the
      occurrence of plants in graveyards reflect the geographic situation of Israel as
      a crossroads in the cultural arena between Asia and Europe. Most of the
      traditions are common to the whole Middle East showing high relatedness to the
      classical world as well as to the present-day Europe.

PMID- 16961932
TI  - The toxicity of cadmium and resulting hazards for human health.
AB  - Cadmium (Cd) has been in industrial use for a long period of time. Its serious
      toxicity moved into scientific focus during the middle of the last century. In
      this review, we discuss historic and recent developments of toxicological and
      epidemiological questions, including exposition sources, resorption pathways and
      organ damage processes.

PMID- 16961933
TI  - Extrapontine myelinolysis presenting as acute parkinsonism.
AB  - BACKGROUND: Extrapontine myelinolysis presenting with extra pyramidal features
      suggestive of parkinsonism may be a challenging clinical syndrome. Clinicians
      should maintain their vigilance while correcting electrolyte imbalances,
      especially with associated co-morbidity. CASE PRESENTATION: A 41-year-old woman
      presented with acute parkinsonism like features while on a holiday. This followed
      slow correction of hyponatraemia after repeated vomiting. MRI changes were
      suggestive of Extrapontine myelinolysis(EPM). This case is at variance with four
      previous cases reported in the medical literature in that the patient made a full
      clinical recovery and the MR changes resolved with symptomatic support alone.
      CONCLUSION: Extrapontine myelinolysis could make a complete recovery with
      symptomatic support alone. During hyponatraemia correction, rapid osmotic shifts
      of fluid that cause hypernatremia, causes myelinolysis rather than absolute serum
      sodium level. Even gradual correction of hyponatraemia can produce myelinolysis,
      especially with pre-existing malnourishment, alcoholism, drug misuse, Addison's
      disease and immuno-suppression. Pallidial sparing is typical of EPM in MRI scans.

PMID- 16961934
TI  - Hypoxia induces telomerase reverse transcriptase (TERT) gene expression in non
      tumor fish tissues in vivo: the marine medaka (Oryzias melastigma) model.
AB  - BACKGROUND: Current understanding on the relationships between hypoxia, hypoxia
      inducible factor-1 (HIF-1) and telomerase reverse transcriptase (TERT) gene
      expression are largely based on in vitro studies in human cancer cells. Although
      several reports demonstrated HIF-1- mediated upregulation of the human TERT gene
      under hypoxia, conflicting findings have also been reported. Thus far, it remains
      uncertain whether these findings can be directly extrapolated to non-tumor
      tissues in other whole animal systems in vivo. While fish often encounter
      environmental hypoxia, the in vivo regulation of TERT by hypoxia in non
      neoplastic tissues of fish remains virtually unknown. RESULTS: The adult marine
      medaka (Oryzias melastigma) was employed as a model fish in this study. We have
      cloned and characterized a 3261-bp full-length TERT cDNA, omTERT, which encodes a
      protein of 1086 amino acids. It contains all of the functional motifs that are
      conserved in other vertebrate TERTs. Motif E is the most highly conserved showing
      90.9-100% overall identity among the fish TERTs and 63.6% overall identity among
      vertebrates. Analysis of the 5'-flanking sequence of the omTERT gene identified
      two HRE (hypoxia-responsive element; nt. - 283 and - 892) cores. Overexpression
      of the HIF-1alpha induced omTERT promoter activity as demonstrated using
      transient transfection assays. The omTERT gene is ubiquitously expressed in fish
      under normoxia, albeit at varying levels, where highest expression was observed
      in gonads and the lowest in liver. In vivo expression of omTERT was significantly
      upregulated in testis and liver in response to hypoxia (at 96 h and 48 h,
      respectively), where concomitant induction of the omHIF-1alpha and erythropoietin
      (omEpo) genes was also observed. In situ hybridization analysis showed that
      hypoxic induction of omTERT mRNA was clearly evident in hepatocytes in the caudal
      region of liver and in spermatogonia-containing cysts in testis. CONCLUSION: This
      study demonstrates for the first time, hypoxic regulation of TERT expression in
      vivo in a whole fish system. Our findings support the notion that hypoxia
      upregulates omTERT expression via omHIF-1 in non-neoplastic fish liver and testis
      in vivo. Overall, the structure and regulation of the TERT gene is highly
      conserved in vertebrates from fish to human.

PMID- 16961935
TI  - Follow-up of newborns treated with extracorporeal membrane oxygenation: a
      nationwide evaluation at 5 years of age.
AB  - INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is a supportive
      cardiopulmonary bypass technique for babies with acute reversible
      cardiorespiratory failure. We assessed morbidity in ECMO survivors at the age of
      five years, when they start primary school and major decisions for their school
      careers must be made. METHODS: Five-year-old neonatal venoarterial-ECMO survivors
      from the two designated ECMO centres in The Netherlands (Erasmus MC--Sophia
      Children's Hospital in Rotterdam, and University Medical Center Nijmegen) were
      assessed within the framework of an extensive follow-up programme. The protocol
      included medical assessment, neuromotor assessment, and psychological assessment
      by means of parent and teacher questionnaires. RESULTS: Seventeen of the 98
      children included in the analysis (17%) were found to have neurological deficits.
      Six of those 17 (6% of the total) showed major disability. Two of those six
      children had a chromosomal abnormality. Three were mentally retarded and
      profoundly impaired. The sixth child had a right-sided hemiplegia. These six
      children did not undergo neuromotor assessment. Twenty-four of the remaining 92
      children (26%) showed motor difficulties: 15% actually had a motor problem and
      11% were at risk for this. Cognitive delay was identified in 11 children (14%).
      The mean IQ score was within the normal range (IQ = 100.5). CONCLUSION: Neonatal
      ECMO in The Netherlands was found to be associated with considerable morbidity at
      five years of age. It appeared feasible to have as many as 87% of survivors
      participate in follow-up assessment, due to cooperation between two centres and
      small travelling distances. Objective evaluation of the long-term morbidity
      associated with the application of this highly invasive technology in the
      immediate neonatal period requires an interdisciplinary follow-up programme with
      nationwide consensus on timing and actual testing protocol.

PMID- 16961936
TI  - The effect of socioeconomic status on three-year mortality after first-ever
      ischemic stroke in Nanjing, China.
AB  - BACKGROUND: Low socioeconomic status (SES) is associated with increased mortality
      after stroke in developed countries. This study was performed to determine
      whether a similar association also exists in China. METHODS: A total of 806
      patients with first-ever ischemic stroke were enrolled in our study. From August
      1999 to August 2005, the three-year all-cause mortality following the stroke was
      determined. Level of education, occupation, taxable income and housing space were
      used as indicators for SES. Stepwise univariate and multivariate COX proportional
      hazards models were used to study the association between the SES measures and
      the three-year mortality. RESULTS: Our analyses confirmed that occupation,
      taxable income and housing space were significantly associated with three-year
      mortality after first-ever stroke. Manual workers had a significant hazard ratio
      of 5.44 (95% CI 2.75 to 10.77) for death within three years when compared with
      non-manual workers. Those in the zero income group had a significant hazard ratio
      of 5.35 (95% CI 2.95 to 9.70) and those in the intermediate income group 2.10
      (95% CI 1.24 to 3.58) when compared with those in the highest income group. Those
      in two of the three groups with the smallest housing space also had significant
      hazard ratios of 2.06 (95% CI 1.16 to 3.65) and 1.68 (95% CI 1.12 to 2.52) when
      compared with those in group with the largest housing space. These hazard ratios
      remained largely unchanged after multivariate adjustment for age, gender,
      baseline cardiovascular disease risk factors, and stroke severity. The analyses
      did not confirm an association with educational level. CONCLUSION: Lower SES has
      a negative impact on the outcome of first-ever stroke in Nanjing, China. This
      confirms the need to improve preventive and secondary care for stroke among low
      SES groups.

PMID- 16961937
TI  - Emergence of physiological rhythmicity in term and preterm neonates in a neonatal
      intensive care unit.
AB  - BACKGROUND: Biological rhythmicity, particularly circadian rhythmicity, is
      considered to be a key mechanism in the maintenance of physiological function.
      Very little is known, however, about biological rhythmicity pattern in preterm
      and term neonates in neonatal intensive care units (NICU). In this study, we
      investigated whether term and preterm neonates admitted to NICU exhibit
      biological rhythmicity during the neonatal period. METHODS: Twenty-four-hour
      continuous recording of four physiological variables (heart rate: HR recorded by
      electrocardiogram; pulse rate: PR recorded by pulse oxymetry; respiratory rate:
      RR; and oxygen saturation of pulse oxymetry: SpO2) was conducted on 187 neonates
      in NICU during 0-21 days of postnatal age (PNA). Rhythmicity was analyzed by
      spectral analysis (SPSS procedure Spectra). The Fisher test was performed to test
      the statistical significance of the cycles. The cycle with the largest peak of
      the periodogram intensities was determined as dominant cycle and confirmed by
      Fourier analysis. The amplitudes and amplitude indexes for each dominant cycle
      were calculated. RESULTS: Circadian cycles were observed among 23.8% neonates in
      HR, 20% in PR, 27.8% in RR and 16% in SpO2 in 0-3 days of PNA. Percentages of
      circadian cycles were the highest (40%) at < 28 wks of gestational age (GA),
      decreasing with GA, and the lowest (14.3%) at > or = 37 wks GA within 3 days of
      PNA in PR and were decreased in the later PNA. An increase of the amplitude with
      GA was observed in PR, and significant group differences were present in all
      periods. Amplitudes and amplitude indexes were positively correlated with
      postconceptional age (PCA) in PR (p < 0.001). Among clinical parameters, oxygen
      administration showed significant association (p < 0.05) with circadian rhythms
      of PR in the first 3 days of life. CONCLUSION: Whereas circadian rhythmicity in
      neonates may result from maternal influence, the increase of amplitude indexes in
      PR with PCA may be related to physiological maturity. Further studies are needed
      to elucidate the effect of oxygenation on physiological rhythmicity in neonates.

PMID- 16961940
TI  - The impact of sleep deprivation and task difficulty on networks of fMRI brain
      response.
AB  - Previous fMRI research has found altered brain response after total sleep
      deprivation (TSD), with TSD effects moderated by task difficulty. Specific models
      of the impact of sleep deprivation and task difficulty on brain response have yet
      to be developed. Differences in networks of fMRI measured brain response during
      verbal encoding in sleep deprived and well-rested individuals were examined with
      structural equation modeling (SEM). During fMRI scanning, 23 healthy volunteers
      memorized words either easy or difficult to recall, 12 (well-rested) and 36 hours
      (sleep deprived) after awaking. A priori models that linked specified regions of
      interest were evaluated, with the focus on the extent to which two left parietal
      regions interacted with the left inferior frontal gyrus (Model 1) or with the
      right inferior frontal gyrus (Model 2). Task difficulty, not TSD, determined
      which model fit the brain response data; Model 2 fit best for hard words before
      and after TSD, whereas Model 1 fit best for easy words. TSD altered the patterns
      of interaction within each of the best fitting models: prefrontal interactions
      with the left inferior parietal lobe were diminished and intra-parietal
      interactions increased. Sleep deprivation and item difficulty produce different
      effects on brain networks involved in verbal learning.

PMID- 16961938
TI  - Efficacy of bifenthrin-impregnated bednets against Anopheles funestus and
      pyrethroid-resistant Anopheles gambiae in North Cameroon.
AB  - BACKGROUND: Recent field studies indicated that insecticide-treated bednets
      (ITNs) maintain their efficacy despite a high frequency of the knock-down
      resistance (kdr) gene in Anopheles gambiae populations. It was essential to
      evaluate ITNs efficacy in areas with metabolic-based resistance. METHODS:
      Bifenthrin was used in this experiment because it is considered a promising
      candidate for bednets impregnation. Nets were treated at 50 mg/m2, a dose that
      has high insecticidal activity on kdr mosquitoes and at 5 mg/m2, a dose that
      kills 95% of susceptible mosquitoes under laboratory conditions with 3 minutes
      exposure. Bednets were holed to mimic physical damage. The trial was conducted in
      three experimental huts from Pitoa, North-Cameroon where Anopheles gambiae
      displays metabolic resistance and cohabits with An. funestus. RESULTS: Bifenthrin
      at 50 mg/m2 significantly reduced anophelines' entry rate (>80%). This was not
      observed at 5 mg/m2. Both treatments increased exophily in An. gambiae, and to a
      lesser extent in An. funestus. With bifenthrin at high dosage, over 60% reduction
      in blood feeding and 75-90% mortality rates were observed in both vectors.
      Despite presence of holes, only a single An. gambiae and two An. funestus females
      were collected inside the treated net, and all were found dead. The same trends
      were observed with low dosage bifenthrin though in most cases, no significant
      difference was found with the untreated control net. CONCLUSION: Bifenthrin
      impregnated bednets at 50 mg/m2 were efficient in the reduction of human-vector
      contact in Pitoa. Considerable personal protection was gained against An.
      funestus and metabolic pyrethroid resistant An. gambiae populations.

PMID- 16961941
TI  - Motor learning in children with spina bifida: intact learning and performance on
      a ballistic task.
AB  - Learning and performance on a ballistic task were investigated in children with
      spina bifida meningomyelocele (SBM), with either upper level spinal lesions (n =
      21) or lower level spinal lesions (n = 81), and in typically developing controls
      (n = 35). Participants completed three phases (20 trials each) of an elbow
      goniometer task that required a ballistic arm movement to move a cursor to one of
      two target positions on a screen, including (1) an initial learning phase, (2) an
      adaptation phase with a gain change such that recalibration of the ballistic arm
      movement was required, and (3) a learning reactivation phase under the original
      gain condition. Initial error rate, asymptotic error rate, and learning rate did
      not differ significantly between the SBM and control groups. Relative to
      controls, the SBM group had reduced volumes in the cerebellar hemispheres and
      pericallosal gray matter (the region including the basal ganglia), although only
      the pericallosal gray matter was significantly correlated with motor adaptation.
      Congenital cerebellar dysmorphology is associated with preserved motor skill
      learning on voluntary, nonreflexive tasks in children with SBM, in whom the
      relative roles of the cerebellum and basal ganglia may differ from those in the
      adult brain.

PMID- 16961942
TI  - Self-regulation and social and behavioral functioning following childhood
      traumatic brain injury.
AB  - This study examined the impact of childhood traumatic brain injury (TBI) on self
      regulation and social and behavioral functioning, and the role of self-regulation
      as a predictor of children's social and behavioral functioning. Participants
      included 65 children with moderate to severe TBI and 65 children without TBI, all
      between 6 and 11 years of age. Self-regulation and social and behavioral
      functioning were assessed 2 to 5 years following injury. Children with TBI
      displayed deficits in self-regulation and social and behavioral functioning,
      after controlling for socioeconomic status (SES), although the magnitude of the
      deficits was not related to injury severity. Self-regulation accounted for
      significant variance in children's social and behavioral functioning, after
      controlling for SES and group membership. Self-regulation may be an important
      determinant of children's social and behavioral functioning following TBI.

PMID- 16961943
TI  - Motor persistence and inhibition in autism and ADHD.
AB  - The present study compared performance of children with Attention
      Deficit/Hyperactivity Disorder (ADHD) and high functioning autism (HFA) with that
      of controls on 4 tasks assessing 2 components of motor control: motor response
      inhibition and motor persistence. A total of 136 children (52 ADHD, 24 HFA, 60
      controls) ages 7 to 13 years completed 2 measures of motor inhibition
      (Conflicting Motor Response and Contralateral Motor Response Tasks) and 2
      measures of motor persistence (Lateral Gaze Fixation and NEPSY Statue). After
      controlling for age, IQ, gender, and basic motor speed, children with ADHD
      performed significantly more poorly than controls on the Conflicting Motor
      Response and Contralateral Motor Response Tasks, as well as on Statue. In
      contrast, children with HFA achieved lower scores than controls only on measures
      of motor persistence, with no concomitant impairment on either motor inhibition
      task. These results are consistent with prior research that has demonstrated
      relatively spared motor inhibition in autism. The findings highlight the utility
      of brief assessments of motor control in delineating the unique neurobehavioral
      phenotypes of ADHD and HFA.

PMID- 16961944
TI  - The effect of cataract surgery on neuropsychological test performance: a
      randomized controlled trial.
AB  - Recent cross-sectional studies have reported strong associations between visual
      and cognitive function, and longitudinal studies have shown relationships between
      visual and cognitive decline in late life. Improvement in cognitive performance
      after cataract surgery has been reported in patients with Mild Cognitive
      Impairment. We investigated whether improving visual function with cataract
      surgery would improve neuropsychological performance in healthy older adults. A
      randomized clinical trial of cataract surgery performed at acute hospitals was
      conducted on 56 patients (mean age 73) with bilateral cataract, after excluding a
      total of 54 patients at the screening stage, of whom 53 did not meet visual
      acuity criteria and one did not have cataract. In-home assessments included
      visual and neuropsychological function, computerized cognitive testing and health
      questionnaires. Results showed no cognitive benefits of cataract surgery in
      cognitively normal adults. We conclude that visual improvement following cataract
      surgery is not strongly associated with an improvement in neuropsychological test
      performance in otherwise healthy adults. Joint associations between visual and
      cognitive function in late life are likely to be due to central factors, and
      unlikely to be strongly related to eye disease. Short-term increased neural
      stimulation from improved visual function does not appear to affect cognitive
      performance.

PMID- 16961945
TI  - Self-generated learning in people with multiple sclerosis.
AB  - Memory impairment is among the most common cognitive deficits in people with
      multiple sclerosis (MS). To remediate this problem, recent research has evaluated
      the benefits of self-generated encoding. These nascent investigations reveal that
      people with MS who have mild memory impairment demonstrate a significant memory
      benefit from self-generated encoding compared with didactic learning. To extend
      prior research, the present experiment included MS patients with moderate-severe,
      rather than just mild, memory impairment. Additionally, the experiment evaluated
      whether self-generated encoding improves memory for activities of daily living
      instead of abstract words. Specifically, the experiment determined whether self
      generated encoding enhanced memory for names, appointments, and object locations.
      In agreement with and extending prior research, MS patients remembered more
      information if it was self-generated rather than didactically presented, and this
      finding occurred despite moderate-severe memory impairment. Furthermore, compared
      with didactic encoding, self-generation enhanced recall of activities of daily
      living. Implications of these findings for cognitive rehabilitation and the
      nature of memory impairment in MS are discussed.

PMID- 16961946
TI  - The attenuation of auditory neglect by implicit cues.
AB  - This study examined implicit semantic and rhyming cues on perception of auditory
      stimuli among nonaphasic participants who suffered a lesion of the right cerebral
      hemisphere and auditory neglect of sound perceived by the left ear. Because
      language represents an elaborate processing of auditory stimuli and the language
      centers were intact among these patients, it was hypothesized that interactive
      verbal stimuli presented in a dichotic manner would attenuate neglect. The
      selected participants were administered an experimental dichotic listening test
      composed of six types of word pairs: unrelated words, synonyms, antonyms,
      categorically related words, compound words, and rhyming words. Presentation of
      word pairs that were semantically related resulted in a dramatic reduction of
      auditory neglect. Dichotic presentations of rhyming words exacerbated auditory
      neglect. These findings suggest that the perception of auditory information is
      strongly affected by the specific content conveyed by the auditory system.
      Language centers will process a degraded stimulus that contains salient language
      content. A degraded auditory stimulus is neglected if it is devoid of content
      that activates the language centers or other cognitive systems. In general, these
      findings suggest that auditory neglect involves a complex interaction of intact
      and impaired cerebral processing centers with content that is selectively
      processed by these centers.

PMID- 16961947
TI  - The role of the basal ganglia in the control of automatic visuospatial attention.
AB  - Cognitive impairments in patients with basal ganglia dysfunction are primarily
      revealed where performance relies on internal, voluntary control processes.
      Evidence suggests that this also extends to impaired control of more automatic
      processes, including visuospatial attention. The present study used a non
      predictive peripheral cueing paradigm to compare and contrast visuospatial
      deficits in patients with Parkinson's disease (PD) with those previously revealed
      in patients with Huntington's disease (HD) (Fielding et al., 2006a). Compared to
      age-matched controls, both PD and HD patients exhibited increased distractibility
      or poor fixation, however only PD patients responded erroneously to cue stimuli
      more frequently than control subjects. All subjects demonstrated initial
      facilitation for valid versus invalid cues following the shorter stimulus-onset
      asynchronies (SOAs) and a performance decrement at the longer SOAs (inhibition of
      return), although there was a clear differentiation between these groups for
      immediate SOAs. Unlike both control and PD subjects, where IOR manifested between
      350 and 1000 msec, IOR was evident as early as 150 msec for HD patients. Further,
      for PD patients, spatially valid cues resulted in hyper-reflexivity following 150
      msec SOAs, with saccadic latencies shorter than those generated in response to un
      cued targets. Thus contrasting deficits were revealed in PD and HD, emphasizing
      the important contribution of the basal ganglia in the control of more automatic
      behaviors

PMID- 16961948
TI  - Motivational processes and autonomic responsivity in Asperger's disorder:
      evidence from the Iowa Gambling Task.
AB  - Asperger's disorder (ASP), like other autism spectrum disorders, is associated
      with altered responsiveness to social stimuli. This study investigated learning
      and responsiveness to nonsocial, but motivational, stimuli in ASP. We examined
      choice behavior and galvanic skin conductance responses (SCRs) during the Iowa
      Gambling Task (IGT; Bechara et al., 1994) in 15 adolescents and young adults with
      ASP and 14 comparison subjects. We examined aspects of learning, attention to
      wins and losses, and response style with a formal cognitive model, the Expectancy
      Valence Learning model (Busemeyer & Stout, 2002). The ASP group did not differ
      from the comparison group in proportions of selections from advantageous decks.
      However, ASP participants showed a distinct pattern of selection characterized by
      frequent shifts between the four IGT decks, whereas comparison participants
      developed clear deck preferences. SCR results showed some evidence of reduced
      responsiveness in the ASP group during the IGT. Results from the cognitive model
      indicated that, in contrast to the comparison group, the ASP group's selections
      were less consistent with the motivational significance they assigned to decks.
      Findings are discussed in the context of the neurobiological substrates
      associated with IGT performance.

PMID- 16961949
TI  - Working memory deficits in multiple sclerosis: comparison between the n-back task
      and the Paced Auditory Serial Addition Test.
AB  - Working memory (WM) deficits are common in multiple sclerosis (MS). The Paced
      Auditory Serial Addition Test (PASAT) is used frequently to measure WM in
      clinical settings. The n-back paradigm is used often in experimental studies of
      WM. One unique component of the n-back task is that it provides a measure of
      reaction time (RT), an additional behavioral index of processing speed and task
      difficulty. Despite the use of both tasks to measure WM, their common variance
      has not been documented. We tested 32 MS patients and 20 controls; performance
      measures were obtained for both tasks. Compared with controls, MS patients
      generally had poorer performance on both the PASAT and n-back task. MS patients
      also had slower RTs on the n-back than controls and showed more slowing than
      controls as a function of WM load. Correlational analyses showed a high
      correspondence between performance measures on the PASAT and n-back. Principal
      components analysis pointed to a common feature of the PASAT, n-back, and
      specific other neuropsychological measures, that is, processing speed. Although
      the PASAT and n-back were shown to have a significant amount of shared variance,
      each test has specific advantages and disadvantages for use in clinical
      populations.

PMID- 16961950
TI  - Detection of inadequate effort on the California Verbal Learning Test-Second
      edition: forced choice recognition and critical item analysis.
AB  - The Forced Choice Recognition (FCR) and the Critical Item Analysis (CIA) indices
      of the California Verbal Learning Test-II (CVLT-II) have been identified by the
      CVLT-II test developers as potentially useful, brief screening indicators of
      effort in neuropsychological assessment. This retrospective study analyzes
      performance on these measures in three groups: (1) clinically referred
      individuals; (2) forensically referred individuals not suspected of inadequate
      effort; and (3) forensically referred individuals whose performance on
      freestanding tests of effort suggested inadequate effort. Performances on FCR
      were analyzed for their relation to actual memory impairment and with regard to
      concrete and abstract distractor endorsement. FCR and CIA performances were
      analyzed for agreement with formal tests of inadequate effort and their test
      characteristics. Incremental validity was assessed by hierarchical logistic
      regression with previously identified indices for detection of inadequate effort
      on the CVLT. Results indicate that (1) FCR and CIA performances are not related
      to decreased memory performance; (2) FCR and CIA indices exhibit higher
      specificity and lower sensitivity, with higher positive predictive value than
      negative predictive value; and (3) FCR and CIA indices exhibit modest incremental
      validity with previously identified indices. Implications for use of FCR and CIA
      indices in inadequate effort detection are discussed

PMID- 16961951
TI  - Impulsivity, reward sensitivity, and decision-making in subarachnoid hemorrhage
      survivors.
AB  - Subarachnoid hemorrhage (SAH) survivors often report psychosocial and emotional
      changes, including a diminished capacity for decision making. However, systematic
      investigations into the nature of the changes have been limited to those patients
      surviving SAH secondary to aneurysms of the anterior communicating artery. This
      study aimed to explore the nature of decision making in survivors of SAH
      secondary to aneurysms of the middle cerebral or posterior communicating artery
      using a series of computerized tasks. Twenty SAH survivors and 20 matched
      controls completed a battery of computerized decision-making tasks. These
      included tasks examining an individual's ability to make probabilistic choices
      and risk-taking behavior, as well as tasks examining aspects of impulsivity. The
      results revealed two key patterns of abnormal decision-making behavior in the SAH
      survivors: altered sensitivity to both reward and punishment, and impulsive
      responding. These complex deficits may contribute to difficulties in daily living
      resulting from apathy, poor judgment, or inhibition in SAH survivors.

PMID- 16961953
TI  - Body side of motor symptom onset in Parkinson's disease is associated with memory
      performance.
AB  - The relation of body side of motor symptom onset in Parkinson's disease (PD) to
      memory measures associated with hemispheric dominance was examined. Fourteen
      patients with right body side motor symptom onset (RPD, inferred left hemisphere
      dysfunction) and 16 patients with left side onset (LPD, right hemisphere
      dysfunction) were administered measures of verbal (Hopkins Verbal Learning Test
      Revised) and visual memory (Brief Visual Memory Test-Revised), that require
      similar task demands and are associated with left or right hemisphere dominance,
      respectively. The LPD group demonstrated poorer visual than verbal memory, both
      within group and in comparison to the RPD group. By contrast, the RPD group
      showed poorer verbal than visual memory within group. These findings suggest that
      side of motor symptom onset is associated with asymmetrical memory dysfunction.

PMID- 16961954
TI  - The Iowa gambling task as a measure of decision making in women with bulimia
      nervosa.
AB  - Persistent chaotic feeding behavior (i.e., bingeing and purging), despite
      consequent adverse health and psychosocial consequences, is central to the
      definition and diagnosis of bulimia nervosa (BN). Repeatedly choosing immediate
      short-term gratification when long-term consequences are deleterious may reflect
      deficits in decision-making ability. However, to date, there has been no
      systematic examination of decision-making ability in individuals diagnosed with
      BN. In the present study, 20 undergraduate women with minimal bulimic symptoms
      (Control Group) and 20 with a diagnosis of BN (BN Group) were administered the
      Iowa Gambling Task (GT). Results indicated that the BN Group performed
      significantly worse on the GT in comparison to the Control Group and GT
      performance was negatively correlated with bulimic symptomatology. The presence
      of BN symptoms also predicted GT performance above and beyond demographic
      variables and depressive symptoms. These findings provide evidence for the
      presence of decision-making deficits in individuals with BN.

PMID- 16961952
TI  - Neuropsychological and neuroimaging changes in preclinical Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a common, devastating form of dementia. With the
      advent of promising symptomatic treatment, the importance of recognizing AD at
      its very earliest stages has increased. We review the extant neuropsychological
      and neuroimaging literature on preclinical AD, focusing on longitudinal studies
      of initially nondemented individuals and cross-sectional investigations comparing
      at-risk with normal individuals. We systematically reviewed 91 studies of
      neuropsychological functioning, structural neuroimaging, or functional
      neuroimaging in preclinical AD. The neuropsychological studies indicated that
      preclinical AD might be characterized by subtle deficits in a broad range of
      neuropsychological domains, particularly in attention, learning and memory,
      executive functioning, processing speed, and language. Recent findings from
      neuroimaging research suggest that volume loss and cerebral blood flow or
      metabolic changes, particularly in the temporal lobe, may be detected before the
      onset of dementia. There exist several markers of a preclinical period of AD, in
      which specific cognitive and biochemical changes precede the clinical
      manifestations. The preclinical indicators of AD reflect early compromise of
      generalized brain integrity and temporal lobe functioning in particular.

PMID- 16961955
TI  - Everyday memory functioning in obsessive- compulsive disorder.
AB  - Memory performance in obsessive-compulsive disorder (OCD) is discussed as a
      pathogenetic risk factor for the emergence of OCD, particularly checking
      compulsions. At present, however, findings are mixed and little is known about
      memory performance in tasks relevant to everyday functioning in patients with
      OCD. For the present study, memory performance was assessed in 31 patients
      diagnosed with OCD and 33 healthy controls with the Rivermead Behavioural Memory
      Test (RBMT), which covers a wide range of verbal and nonverbal memory components
      as well as prospective memory. OCD patients performed comparably to healthy
      controls on the memory task for verbal, nonverbal, and prospective memory (p >
      .1). According to norm values, memory performance was unimpaired in most OCD
      patients. The present findings further challenge a broad account of the "memory
      deficit" hypothesis of OCD and compulsive checking, respectively.

PMID- 16961956
TI  - Impairment of memory organization in patients with schizophrenia or schizotypal
      disorder.
AB  - Verbal learning and the organization of memory in patients with schizophrenia or
      schizotypal disorder were compared with normal subjects. Three indices of memory
      organization (semantic clustering, serial clustering, and subjective clustering)
      were calculated from participants' responses on the Japanese Verbal Learning
      Test. Schizophrenic and schizotypal patients showed similar decrements in
      semantic organization compared with normal subjects. Neither patient group showed
      any effect of learning on their use of semantic organization, although both
      groups recalled more items as the number of trials increased. These results
      suggest that impairment of memory organization is a common characteristic of
      schizophrenia spectrum disorders.

PMID- 16961957
TI  - Everyday actions are activities of daily living.

PMID- 16961961
TI  - Monge: The Verriest lecture, Lyon, July 2005.
AB  - In 1789, when neither the physical basis of hue nor the retinal basis of color
      perception was established, the mathematician Gaspard Monte stated firmly that
      our color perceptions do not depend on the absolute value of the physical
      variable, but are influenced by the context and in particular by our estimate of
      the illuminant. He used this insight to explain color contrast effects and the
      Paradox of Monge (the desaturation of red objects seen through a red filter). He
      proposed that we can estimate the chromaticity of the illuminant in any scene
      because all surfaces reflect to us varying mixtures of (i) the body color and
      (ii) a specular component that represents the illuminant. He also realized that
      white objects have a special property: Provided that they are illuminated by a
      single illuminant, such objects exhibit no variation in chromaticity across their
      surface. Thus at least one of the unique hues exists as an external reference on
      which observers can agree. It is suggested that other unique hues may also have a
      basis in the external world.

PMID- 16961962
TI  - Surface color perception in three-dimensional scenes.
AB  - Researchers studying surface color perception have typically used stimuli that
      consist of a small number of matte patches (real or simulated) embedded in a
      plane perpendicular to the line of sight (a "Mondrian," Land & McCann, 1971).
      Reliable estimation of the color of a matte surface is a difficult if not
      impossible computational problem in such limited scenes (Maloney, 1999). In more
      realistic, three-dimensional scenes the difficulty of the problem increases, in
      part, because the effective illumination incident on the surface (the light
      field) now depends on surface orientation and location. We review recent work in
      multiple laboratories that examines (1) the degree to which the human visual
      system discounts the light field in judging matte surface lightness and color and
      (2) what illuminant cues the visual system uses in estimating the flow of light
      in a scene.

PMID- 16961964
TI  - Color naming, unique hues, and hue cancellation predicted from singularities in
      reflection properties.
AB  - Psychophysical studies suggest that different colors have different perceptual
      status: red and blue for example are thought of as elementary sensations whereas
      yellowish green is not. The dominant account for such perceptual asymmetries
      attributes them to specificities of the neuronal representation of colors.
      Alternative accounts involve cultural or linguistic arguments. What these
      accounts have in common is the idea that there are no asymmetries in the physics
      of light and surfaces that could underlie the perceptual structure of colors, and
      this is why neuronal or cultural processes must be invoked as the essential
      underlying mechanisms that structure color perception. Here, we suggest a
      biological approach for surface reflection properties that takes into account
      only the information about light that is accessible to an organism given the
      photopigments it possesses, and we show that now asymmetries appear in the
      behavior of surfaces with respect to light. These asymmetries provide a
      classification of surface properties that turns out to be identical to the one
      observed in linguistic color categorization across numerous cultures, as pinned
      down by cross cultural studies. Further, we show that data from psychophysical
      studies about unique hues and hue cancellation are consistent with the viewpoint
      that stimuli reported by observers as special are those associated with this
      singularity-based categorization of surfaces under a standard illuminant. The
      approach predicts that unique blue and unique yellow should be aligned in
      chromatic space while unique red and unique green should not, a fact usually
      conjectured to result from nonlinearities in chromatic pathways.

PMID- 16961963
TI  - Three-dimensional shape perception from chromatic orientation flows.
AB  - The role of chromatic information in 3-D shape perception is controversial. We
      resolve this controversy by showing that chromatic orientation flows are
      sufficient for accurate perception of 3-D shape. Chromatic flows required less
      cone contrast to convey shape than did achromatic flows, thus ruling out
      luminance artifacts as a problem. Luminance artifacts were also ruled out by a
      protanope's inability to see 3-D shape from chromatic flows. Since chromatic
      orientation flows can only be extracted from retinal images by neurons that are
      responsive to color modulations and selective for orientation, the psychophysical
      results also resolve the controversy over the existence of such neurons. In
      addition, we show that identification of 3-D shapes from chromatic flows can be
      masked by luminance modulations, indicating that it is subserved by orientation
      tuned neurons sensitive to both chromatic and luminance modulations.

PMID- 16961965
TI  - Color constancy in natural scenes explained by global image statistics.
AB  - To what extent do observers' judgments of surface color with natural scenes
      depend on global image statistics? To address this question, a psychophysical
      experiment was performed in which images of natural scenes under two successive
      daylights were presented on a computer-controlled high-resolution color monitor.
      Observers reported whether there was a change in reflectance of a test surface in
      the scene. The scenes were obtained with a hyperspectral imaging system and
      included variously trees, shrubs, grasses, ferns, flowers, rocks, and buildings.
      Discrimination performance, quantified on a scale of 0 to 1 with a color
      constancy index, varied from 0.69 to 0.97 over 21 scenes and two illuminant
      changes, from a correlated color temperature of 25,000 K to 6700 K and from 4000
      K to 6700 K. The best account of these effects was provided by receptor-based
      rather than colorimetric properties of the images. Thus, in a linear regression,
      43% of the variance in constancy index was explained by the log of the mean
      relative deviation in spatial cone-excitation ratios evaluated globally across
      the two images of a scene. A further 20% was explained by including the mean
      chroma of the first image and its difference from that of the second image and a
      further 7% by the mean difference in hue. Together, all four global color
      properties accounted for 70% of the variance and provided a good fit to the
      effects of scene and of illuminant change on color constancy, and, additionally,
      of changing test-surface position. By contrast, a spatial-frequency analysis of
      the images showed that the gradient of the luminance amplitude spectrum accounted
      for only 5% of the variance.

PMID- 16961966
TI  - Color constancy in natural scenes with and without an explicit illuminant cue.
AB  - Observers can generally make reliable judgments of surface color in natural
      scenes despite changes in an illuminant that is out of view. This ability has
      sometimes been attributed to observers' estimating the spectral properties of the
      illuminant in order to compensate for its effects. To test this hypothesis, two
      surface-color-matching experiments were performed with images of natural scenes
      obtained from high-resolution hyperspectral images. In the first experiment, the
      sky illuminating the scene was directly visible to the observer, and its color
      was manipulated. In the second experiment, a large gray sphere was introduced
      into the scene so that its illumination by the sun and sky was also directly
      visible to the observer, and the color of that illumination was manipulated.
      Although the degree of color constancy varied across this and other variations of
      the images, there was no reliable effect of illuminant color. Even when the sky
      was eliminated from view, color constancy did not worsen. Judging surface color
      in natural scenes seems to be independent of an explicit illuminant cue.

PMID- 16961967
TI  - Global integration of local color differences in transparency perception: An fMRI
      study.
AB  - In normal viewing, the visual system effortlessly assigns approximately constant
      attributes of color and shape to perceived objects. A fundamental component of
      this process is the compensation for illuminant variations and intervening media
      to recover reflectance properties of natural surfaces. We exploited the
      phenomenon of transparency perception to explore the cortical regions implicated
      in such processes, using fMRI. By manipulating the coherence of local color
      differences around a region in an image, we interfered with their global
      perceptual integration and thereby modified whether the region appeared
      transparent or not. We found the major cortical activation due to global
      integration of local color differences to be in the anterior part of the
      parahippocampal gyrus. Regions differentially activated by chromatic versus
      achromatic geometric patterns showed no significant differential response related
      to the coherence/incoherence of local color differences. The results link the
      integration of local color differences in the extraction of a transparent layer
      with sites activated by object-related properties of an image.

PMID- 16961968
TI  - L and M cone proportions in polymorphic New World monkeys.
AB  - Platyrrhine monkeys typically have only a single X-chromosome opsin gene. Alleles
      of this gene code for multiple versions of middle- to long-wavelength cone
      photopigments. X-chromosome inactivation provides heterozygous females with a
      retinal mosaic of cones containing either of two types of M and L pigment, thus
      establishing the photopigment basis for trichromatic color vision. This study
      examined the proportions of L and M cones created by this process. For that
      purpose, electroretinogram flicker photometry was used to obtain complete
      spectral sensitivity functions from 60 heterozygous female monkeys drawn from
      seven genera of platyrrhine monkeys. To obtain estimates of cone proportions,
      these functions were subsequently fit with linear combinations of L and M cone
      fundamentals that were derived from similar recordings made on conspecific
      animals having only one type of M/L pigment. Consistent with a random X
      chromosome inactivation process, the average L:M cone weighting across the sample
      was close to unity. At the same time, there were significant individual
      variations in L:M cone proportions. The genesis of this variation and its
      implications for seeing are discussed.

PMID- 16961969
TI  - Mutually exclusive expression of the L and M pigment genes in the human
      retinoblastoma cell line WERI: Resetting by cell division.
AB  - The key steps in the evolution of full trichromatic color vision in primates
      include duplication of the ancestral pigment gene to form the L and M pigment
      gene array on the X chromosome, mutually exclusive expression of the L and M
      pigment genes in cone photoreceptors, and formation of a retinal mosaic with
      randomly distributed L and M cones. Previous work using transgenic mice has
      indicated that a locus control region adjacent to this array of genes plays an
      important role in their mutually exclusive expression in respective cone cells
      (Smallwood et al., 2002). However, the mechanism by which this is accomplished is
      unknown. We searched for a cellular model system to investigate the mechanism of
      this mutually exclusive expression. We previously showed that the
      undifferentiated human retinoblastoma cell line WERI expresses L and M cone opsin
      but not rod opsin genes. We now show that WERI cells express the L and M pigment
      genes in a mutually exclusive manner, in that either L or M pigment mRNA is
      expressed in a single cell. Importantly, clonal analysis showed that single WERI
      cells that express either L or M generate, upon cell division produce, a mixed
      population of L- or M-expressing cells. These results indicate, first, that cell
      division resets L or M pigment gene expression, most likely due to disassembly
      and reassembly of LCR-promoter DNA-protein complexes during cell division.
      Second, a retinal mosaic with near-random distribution of L and M cones may have
      been generated automatically after duplication of the ancestral gene to form the
      L and M pigment genes. Third, determination of L and M cone identity may not
      require external molecular cues during differentiation, and is consistent with
      the idea that L and M cones are not intrinsically different.

PMID- 16961970
TI  - Topography of long- and middle-wavelength sensitive cone opsin gene expression in
      human and Old World monkey retina.
AB  - The topographical distributions of the relative ratio of long- (L) and middle-
      (M) wavelength sensitive cone opsin messenger RNA (mRNA) in human and baboon
      retinas were mapped using real-time polymerase chain reaction. The L:M mRNA ratio
      increased in a central-to-peripheral gradient in both species, being quite
      pronounced for humans.

PMID- 16961971
TI  - An urn model of the development of L/M cone ratios in human and macaque retinas.
AB  - A model of the development of L/M cone ratios in the Old World primate retina is
      presented. It is supposed that during gestation, the cone cycles randomly between
      states in which it transcribes either L or M opsin. The current state determines
      and increases the probability that it will transcribe the same opsin in future
      cycles. These assumptions are sufficient to formalize the process as a Markov
      chain that can be modeled as an urn containing two types of balls, L and M.
      Drawing one ball results in the increase of its species and the decrease of the
      other. Over the long run, the urn will become populated with a single type of
      ball. This state corresponds to the photoreceptor adopting a fixed identity for
      its lifetime. We investigate the effect of the number of states and the rule that
      regulates the advantage of transition toward one cone type or another on the
      relation between fetal and adult L/M cone ratios. In the range of 100 to 1000
      states, small variations of the initial L/M ratio or the transition advantage can
      each generate large changes in the final L/M ratio, in qualitative accord with
      the variation seen in human adult retinas. The time course to attain stable L/M
      ratios also varies with these parameters. If it is believed that the cycling
      follows a circadian rhythm, then final L/M cone ratios would be expected to
      stabilize shortly after birth in the human being and the macaque.

PMID- 16961972
TI  - Compound heterozygous CNGA3 mutations (R436W, L633P) in a Japanese patient with
      congenital achromatopsia.
AB  - Congenital achromatopsia is a stationary retinal disorder with autosomal
      recessive inheritance that is characterized by loss of color discrimination, low
      visual acuity, photophobia, and nystagmus. This disorder has been shown to be
      associated with CNGA3, CNGB3, and GNAT2 mutations, and the frequency of mutations
      in the CNGA3 gene (encoding alpha subunit of the cone-specific cGMP-gated cation
      channel) was 23-33% in European populations. The aim of this study was to test
      the hypothesis that CNGA3 mutations are also responsible for congenital
      achromatopsia in Japanese patients. DNA from venous blood samples from a total of
      14 patients from 13 Japanese pedigrees was prepared. Mutation screening of the
      CNGA3 gene was performed using direct sequencing and PCR-single-strand
      conformation polymorphism analysis. Compound heterozygous missense mutations
      (p.R436W and p.L633P, the latter of which was novel) were identified in one
      patient only, a 22-year-old female. Neither of these two mutations was found in
      150 Japanese control individuals. The patient's parents and sister carried one of
      these mutations each but were not affected. No mutations in the CNGB3 or GNAT2
      genes were identified in the patient. Clinically, best-corrected visual acuity
      was 0.1 in both eyes. No specific findings were obtained in funduscopy. Optical
      coherence topography revealed a normal foveal thickness but a 20% decrease in
      parafoveal thickness. Ganzfeld full-field electroretinograms (ERGs) showed normal
      responses in rod and mixed rod-plus-cone ERGs but no response in cone or 30-Hz
      flicker ERGs. Spectral sensitivity on a white background revealed a curve with
      only one peak at around 500 nm, which fits the absorption spectrum of human
      rhodopsin. L633, conserved among vertebrate orthologs of human CNGA3, is a
      hydrophobic residue forming part of the carboxy-terminal leucine zipper (CLZ)
      domain, which is functionally important in the mediation of intracellular
      interactions. To our knowledge, this is the first report of a Japanese complete
      achromat with CNGA3 mutations, and of any patient with a missense mutation within
      the CLZ domain. The outcome suggests low frequency (7%, 1/14) of CNGA3 mutations
      in Japanese patients.

PMID- 16961974
TI  - Novel form of a single X-linked visual pigment gene in a unique dichromatic color
      vision defect.
AB  - In normal trichromats, the long- (L) and middle-wavelength-sensitive (M) pigment
      genes are arranged in a head-to-tandem array on the X chromosome. Two amino acids
      at positions 277 and 285, encoded by exon 5 of the L and M genes, respectively,
      are essential for the spectral difference between L and M pigments whose spectral
      peaks are at approximately 560 and 530 nm. Intragenic or intergenic unequal
      crossing-over commonly occurs between the highly homologous L and M genes,
      resulting in red-green color vision deficiencies. The dichromacy is usually
      associated with a single L gene for deuteranopia or a single 5' L-M 3' hybrid
      gene with M-gene exon 5 for protanopia. We clinically diagnosed a total of 88
      male dichromats using a Nagel model I anomaloscope, which included one
      unclassified subject in addition to 31 protanopes and 56 deuteranopes. The
      objective of this study was to characterize the phenotype of the subject and to
      determine the genotype of his X-linked pigment genes. The subject accepted not
      only any red-green mixture but also an extended yellow-scale range at each
      matching point (i.e. 20 to 32 scale units at the green primary and 3.5 to 6 scale
      units at the red primary). The slopes of regression lines were in the range of 
      0.34 to -0.23, while the mean slopes for the protanopes and deuteranopes were 
      0.38 and -0.01, respectively. Spectral sensitivity tests showed that the
      subject's curve was shifted between the protanope and deuteranope curves.
      Molecular analysis revealed a novel form of a single pigment gene with a unique
      arrangement of exon 5 (Y277 from the L gene and A285 from the M gene). The
      predicted lambdamax (541 to 546 nm) of the unique pigment was closer to the M
      than to the L pigment. Our outcome suggests that intragenic unequal crossing-over
      may have occurred between amino acid positions 279 and 283.

PMID- 16961973
TI  - A novel mutation in the short-wavelength-sensitive cone pigment gene associated
      with a tritan color vision defect.
AB  - Inherited tritan color vision deficiency is caused by defects in the function of
      the short-wavelength-sensitive (S) cones. This heterozygous group of disorders
      has an autosomal dominant pattern of inheritance. Amino acid variations of the S
      cone opsin are rare and all that have been identified thus far are associated
      with inherited tritan color vision defects. Here we report the identification of
      a 30-year-old male who made errors on standard color vision tests consistent with
      the presence of a mild tritan color vision deficiency. We tested the hypothesis
      that his color vision impairment was due to a mutation in the S cone photopigment
      gene. He was found to be heterozygous for a mutation that caused the amino acid
      proline to be substituted in place of a highly conserved leucine at amino acid
      position 56 in the S cone opsin. This mutation was absent in 564 S cone
      photopigment genes from 282 subjects who did not make tritan errors. Thus, we
      conclude that this mutation disrupts the normal function of S cones.

PMID- 16961975
TI  - Convergence of experimental multiple Rayleigh matches to peak L- and M
      photopigment sensitivity estimates.
AB  - Shift in the wavelength of peak sensitivity of the cone photo pigments is a major
      cause of inter-individual variations in the Rayleigh match. Normal color
      observers performed multiple Rayleigh matches (i.e., a series of seven Rayleigh
      type color matches using various sets of test and primary lights) in order to
      derive estimates of the M- and L-photo pigment wavelengths of maximum absorbance.
      We predicted the ratio of incident radiances Pr/Pg for a range of plausible
      values in terms of wavelength of the peak sensitivity of the M-cone and L-cone.
      An algorithm allowed us to adjust the values of the peak wavelength of the cone
      photo pigments in order to minimize the sum of squared differences between
      predicted and real results of matches. To create candidate M-cone and L-cone
      photo pigments that best predict the set of equation values, we used the low
      density spectral absorbance curves of the M-cone and L-cone photo pigments
      respectively, as tabulated by Stockman and Sharpe (2000), and shifted each
      template along a logarithmic wavelength scale. For all observers, the system of
      seven Rayleigh-like equations converges to a unique solution. M- and L-cone photo
      pigments are estimated separately. The distribution of the wavelength of maximum
      sensitivity of the photo pigments includes a cluster. Only a few women's results
      lie outside the cluster. The choice of the template has a considerable influence
      on the convergence of the algorithm.

PMID- 16961976
TI  - Independent variation of retinal S and M cone photoreceptor topographies: A
      survey of four families of mammals.
AB  - In mammals, cone photoreceptor subtypes are thought to establish topographies
      that reflect the species-relevant properties of the visual environment. Middle-
      to long-wavelength-sensitive (M) cones are the dominant population and in most
      species they form an area centralis at the visual axis. Short-wavelength
      sensitive (S) cone topographies do not always match this pattern. We here
      correlate the interrelationship of S and M cone topographies in representatives
      of several mammalian orders with different visual ecology, including man,
      cheetah, cat, Eurasian lynx, African lion, wild hog, roe deer, and red deer.
      Retinas were labeled with opsin antisera and S and M cone distributions as well
      as S/M cone ratios were mapped. We find that species inhabiting open environments
      show M cone horizontal streaks (cheetah, pig, deer). Species living in structured
      habitats (tiger, lynx, red deer) have increased S cone densities along the
      retinal margin. In species with active vision (cheetah, bear, tiger, man), S cone
      distributions are more likely to follow the centripetal M cone gradients. Small
      species show a ventral bias of peak S cone density which either matches the peak
      of M cone density in a temporal area centralis (diurnal sciurid rodents, tree
      shrews) or not (cat, manul, roe deer). Thus, in addition to habitat structure,
      physical size and specific lifestyle patterns (e.g. food acquisition) appear to
      underlie the independent variations of M and S cone topographies.

PMID- 16961977
TI  - Response of carp (Cyprinus carpio) horizontal cells to heterochromatic flicker
      photometry.
AB  - The objective of the present work was to determine the interaction of cone inputs
      in the response of horizontal cells using heterochromatic flicker photometry
      (HFP). Intracellular electrophysiological recordings were made in horizontal
      cells of isolated retinae of carp maintained in physiological solution, with the
      receptor side up. Sharp glass microelectrodes filled with 3 M KCl solution with
      resistances between 100 and 120 M Omega were used. Stimuli comprised six cycles
      of two 6-Hz sinusoidal light waves in counterphase adjusted for the same number
      of quanta: a green light (550 nm) from a monochromator with a Xenon lamp and an
      LED red light (628 nm). The stimulation program consisted of 10 steps with the
      550-nm wave at constant amplitude, while the 628-nm wave varied in increments of
      10% up to 100%, followed by another 10 steps with the 628-nm wave at constant
      amplitude while the 550-nm wave varied in increments of 10% up to 100%. We
      recorded responses from four different horizontal cell classes: H1 (monophasic,
      broadband, n = 37), H2 (biphasic, red-green color-opponent, n = 13), and H3
      (biphasic, blue-yellow color-opponent, n = 2) cone horizontal cells; and RH
      (monophasic, broadband, n = 3) rod horizontal cells. H1 and RH horizontal cells
      showed a similar cancellation point at a heterochromatic mixture consistent with
      mixed inputs from 630- and 550-nm cones. No cancellation point was found for the
      H2 cell class. Fish H1 cells add cone inputs and signal "luminance" in light
      levels appropriate for cone stimulation. The same occurs with RH cells, which
      also signal "luminance," but in light levels appropriate for rod work. For both
      cell classes there is an HFP cancellation point occurring at a combination of 628
      nm and 550-nm lights in opposing phase that leads to the cancellation of the
      cell's response. No cancellation was found for H2 and H3 cells, which are the
      chromatically opponent horizontal cells in lower vertebrates.

PMID- 16961979
TI  - Visual evoked potentials to red-green stimulation in schoolchildren.
AB  - The aim is to study chromatic visual evoked potentials (VEP) to isoluminant red
      green (R-G) stimulus in schoolchildren. Sixty children (7-19 years) with normal
      color vision were examined, 30 binocularly and 30 monocularly. The isoluminant
      point was determined for each child subjectively by using heterochromatic flicker
      photometry, and objectively from recordings. The stimulus was a 7 degrees circle
      composed of horizontal sinusoidal gratings, with spatial frequency 2
      cycles/degrees and 90% contrast, presented in onset-offset mode. VEP were
      recorded from Oz (mid-occipital) position. Age-dependent waveform changes and
      changes of the positive and negative wave were studied to both binocular and
      monocular R-G stimulation. Age-dependent waveform changes were observed to
      binocular and monocular R-G stimulation. In younger children the positive wave
      was prominent, whereas in older children also the negative wave became more
      evident. The latency of the positive wave decreased linearly with age to R-G
      binocular stimulation. To monocular stimulation no significant changes of the
      latency were observed. The amplitude of the positive wave dropped exponentially
      with age to binocular and monocular stimulation. The latency of the negative wave
      increased linearly with age to binocular and monocular stimulation, whereas the
      amplitude did not show age-dependent changes. These findings suggest that the
      chromatic VEP response undergoes evident age-dependent changes during the school
      age period.

PMID- 16961978
TI  - Do magnocellular and parvocellular ganglion cells avoid short-wavelength cone
      input?
AB  - We recently developed a new technique to measure cone inputs to visual neurons
      and used this technique to seek short-wavelength-sensitive (S) cone inputs to
      parasol, magnocellular (MC) and midget, parvocellular (PC) ganglion cells. Here,
      we compare our physiological measurements of S-cone weights to those predicted by
      a random wiring model that assumes cells' receptive fields receive input from
      mixed cone types. The random wiring model predicts the average weights of S-cone
      input to be similar to the total percentage of S-cones but with considerable
      scatter, and the S-cone input polarity to be consistent with that of PC cells'
      surround and of MC cells' center. This is not consistent with our physiological
      measurements. We suggest that the ganglion cells' receptive fields may have a
      mechanism to avoid S-cone inputs, as is the case in the H1 horizontal cells.
      Previous reports of S-cone inputs, in particular substantial input to MC cells,
      are likely to reflect variation in prereceptoral filtering and/or the failure to
      correct for variation in macular pigment.

PMID- 16961980
TI  - Transitions between color categories mapped with a reverse Stroop task.
AB  - In the reverse Stroop task, observers are instructed to ignore the ink color in
      which a color word is printed (the distractor color) and to respond to the
      meaning of the color word (the target). Reaction times (RTs) are faster with
      congruent combinations when the ink color matches the word than with incongruent
      combinations when the ink color does not match the word. We manipulated the
      distracting ink color from congruent to incongruent and measured the transition
      from facilitation to interference. In Experiment 1, we confirmed that this
      transition could be assessed independently from the contextual influence of
      particular sets of stimuli and responses, implying that the color space in which
      interference and facilitation occurs is generalizable. In Experiment 2, we
      obtained reverse Stroop data for transitions between red and yellow, yellow and
      green, green and blue, and blue and red, and compared them with independent
      estimates of color appearance obtained by hue scaling for the same chromaticity
      samples. We find that the magnitude of the reverse Stroop effect can provide a
      reliable index of the similarity of color appearance between the distracting
      chromaticity and the color category represented by the target color word.
      Moreover, it will allow us to quantify the mapping between the chromaticity space
      defined at the cone photoreceptors and a cognitive color space defined at an
      advanced level of neural processing.

PMID- 16961981
TI  - Absence of binocular summation, eye dominance, and learning effects in color
      discrimination.
AB  - We evaluated binocular summation, eye dominance, and learning in the Trivector
      and Ellipses procedures of the Cambridge Colour Test (CCT). Subjects (n = 36, 18
      30 years old) were recruited among students and staff from the University of Sao
      Paulo. Inclusion criteria were absence of ophthalmological complaints and best
      corrected Snellen VA 20/20 or better. The subjects were tested in three randomly
      selected eye conditions: binocular, monocular dominant eye, and nondominant eye.
      Results obtained in the binocular and monocular conditions did not differ
      statistically for thresholds measured along the protan, deutan, and tritan
      confusion axes (ANOVA, P > 0.05). No statistical difference was detected among
      discrimination ellipses obtained in binocular or monocular conditions (ANOVA, P >
      0.05), suggesting absence of binocular summation or of an effect of eye
      dominance. Possible effects of learning were examined by comparing successive
      thresholds obtained in the three testing conditions. There was no evidence of
      improvement as a function of testing order (ANCOVA, P > 0.05). We conclude that
      CCT thresholds are not affected by binocularity, eye dominance, or learning. Our
      results differ from those found by Verriest et al. (1982) using the Farnsworth
      Munsell 100 Hue test and Hovis et al. (2004) using the Farnsworth-Munsell panel D
      15 test.

PMID- 16961983
TI  - Temporal nulling of induction from spatial patterns modulated in time.
AB  - Temporally varying chromatic-inducing light was used to infer receptive-field
      organization. Time-varying shifts in color appearance within a test field were
      induced by a surrounding chromatic pattern; the shifts were then nulled by adding
      a time-varying stimulus to the test area so the observer perceived a steady test.
      This method measured chromatic induction without requiring an observer to judge
      the color appearance of the test. The induced color shifts were consistent with a
      +s/-s spatially antagonistic neural receptive field, which also accounts for
      color shifts induced by static chromatic patterns (Monnier & Shevell, 2003,
      Monnier & Shevell, 2004). The response of this type of receptive-field, which is
      found only in the visual cortex, increases with S-cone stimulation at its center
      and decreases with S-cone stimulation within its surround. The measurements also
      showed a negligible influence of temporal inducing frequency in the range 0.5-4
      Hz.

PMID- 16961982
TI  - Paradoxical shifts in human color sensitivity caused by constructive and
      destructive interference between signals from the same cone class.
AB  - Paradoxical shifts in human color (spectral) sensitivity occur on deep-red (658
      nm) background fields. As the radiance of the deep-red background is increased
      from low to moderate levels, the spectral sensitivity for detecting 15-Hz flicker
      shifts toward shorter wavelengths, although by more than is predicted by
      selective chromatic adaptation (e.g., Eisner & MacLeod, 1981; Stromeyer et al.,
      1987; Stockman et al., 1993). Remarkably, though, at higher background radiances,
      the spectral sensitivity then shifts precipitously back towards longer
      wavelengths. Here, we show that both effects are due in large part to destructive
      and constructive interference between signals generated by the same cone type.
      Contrary to the conventional model of the human visual system, the M- and L-cone
      types contribute not just the customary fast signals to the achromatic or
      luminance pathway, but also slower signals of the same or opposite sign. The
      predominant signs of the slow M- and L-cone signals change with background
      radiance, but always remain spectrally opposed (M-L or L-M). Consequently, when
      the slow and fast signals from one cone type destructively interfere, as they do
      near 15 Hz, those from the other cone type constructively interfere, causing the
      paradoxical shifts in spectral sensitivity. The shift in spectral sensitivity
      towards longer wavelengths is accentuated at higher temporal frequencies by a
      suppression of fast M-cone signals by deep-red fields.

PMID- 16961984
TI  - Induced steady color shifts from temporally varying surrounds.
AB  - The color appearance of a physically steady central region can appear to vary
      over time if a surrounding chromatic light varies in time. The induced temporal
      variation, however, is strongly attenuated at surround temporal frequencies above
      approximately 3 Hz. At these higher temporal frequencies, the central region
      appears steady (De Valois et al., 1986). The posited explanation is a cortical
      low-pass temporal filter. Here, we investigate whether higher temporal-frequency
      surrounds induce color shifts in the steady appearance of the central test.
      Surrounds modulated in time along the l or s chromatic direction of MacLeod
      Boynton color space were symmetric around equal-energy white (EEW). The temporal
      frequency of the surround was varied. If observers perceived the central test to
      be temporally modulating between two points in time, they set two separate
      matches to the extreme points of this modulation. If the central test appeared
      steady in time, then color matches were made to this steady appearance.
      Corroborating previous reports, measurements showed that surround temporal
      frequencies below approximately 3 Hz induced temporal modulation. At higher
      temporal frequencies, however, the surround induced steady color shifts, compared
      to a steady surround at its time average (EEW). The measurements imply that a
      nonlinear neural process affects chromatic induction from time-varying context.

PMID- 16961985
TI  - Inhibition or facilitation of return: Does chromatic component count?
AB  - Inhibitory effects have been reported when a target is preceded by a cue of the
      same color and location. Color-based inhibition was found using red and blue
      nonisoluminant stimuli (Law et al., 1995). Here we investigate whether this
      phenomenon depends on the chromatic subsystem involved by employing isoluminant
      colors varying along either the violet-yellow or purple-turquoise cardinal axis.
      Experiment 1 replicated Law et al.'s study: After fixating magenta, either a red
      or blue cue was presented, followed by a magenta "neutral attractor," and,
      finally, by a red or blue target. In Experiment 2, violet and yellow, cue or
      target, varied along a tritan confusion line in the CIE 1976 chromaticity
      diagram. In Experiment 3, purple and turquoise, cue or target, varied along a
      deutan confusion line in the CIE 1976 chromaticity diagram. Normal trichromats (n
      = 19) participated in all three experiments. In Experiment 1, color repetition
      indeed resulted in longer reaction times (RTs) (4.7 ms, P = 0.038). In Experiment
      2, however, no significant color repetition effect was found; RTs to violet and
      yellow were not significantly different, though tending toward slower responses
      (2 ms) for violet repetition but faster (5 ms) for yellow. Experiment 3 also
      showed no color repetition effect (P = 0.58); notably, RTs were overall faster
      for purple than for turquoise (22 ms, P 0.05), but faster for turquoise (7 ms, P
      > 0.05). These findings demonstrate that color repetition is not always
      inhibitory but may turn facilitatory depending on the colors employed. The
      results indicate that disengagement of attention is an unlikely mechanism to be
      the sole explanation of previously reported color-based inhibition of return. We
      suggest a complementary, perceptual explanation: response (dis)advantage depends
      on whether the stimuli are isoluminant and on the opponent chromatic subsystem
      involved. The choice of the colors employed and the cue-attractor-target
      constellation also may be of significance.

PMID- 16961986
TI  - Spatial and temporal chromatic contrast: Effects on chromatic discrimination for
      stimuli varying in L- and M-cone excitation.
AB  - Discrimination for equiluminant chromatic stimuli that vary in L- and M-cone
      excitation depends on the chromaticity difference between the test field and the
      surrounding area. The current study investigated the effect of the proximity in
      space and time of a surround to the test field on chromatic contrast
      discrimination. The experimental paradigm isolated spatial, temporal, and spatial
      and-temporal chromatic contrast effects on discrimination. Chromatic contrast
      discrimination thresholds were assessed by a four-alternative spatial forced
      choice procedure. Stimuli were either metameric to the equal energy spectrum, or
      varied in L-cone activation along a line of constant S-cone activation. A model
      based on primate parvocellular pathway physiology described the data. Spatial and
      temporal contrast produced equivalent reductions in chromatic discriminability as
      the chromatic difference between the test and surround increased. For all test
      chromaticities, discrimination was best in the absence of chromatic contrast.
      Chromatic contrast discrimination is determined by either the spatial or temporal
      contrast component of the signal.

PMID- 16961987
TI  - Cone opponency in the near peripheral retina.
AB  - Changes of color perception in the peripheral field are measured using an
      asymmetric simultaneous matching paradigm. The data confirm previous observations
      in that saturation changes can be neutralized if the test target is increased in
      size. However, this compensation does not apply to hue shifts. We show that some
      hues remain unchanged with eccentricity whereas others exhibit substantial
      changes. Here the color shifts are plotted in terms of a second-stage cone
      opponent model. The data suggest that the S-L+M channel is more robust to
      increasing eccentricity than the L-M channel. Observations are interpreted in
      terms of the known underlying morphological and physiological differences in
      these channels.

PMID- 16961988
TI  - The gap effect is exaggerated in parafovea.
AB  - In central vision, the discrimination of colors lying on a tritan line is
      improved if a small gap is introduced between the two stimulus fields. Boynton et
      al. (1977) called this a "positive gap effect." They found that the effect was
      weak or absent for discriminations based on the ratio of the signals of long-wave
      and middle-wave cones; and even for tritan stimuli, the gap effect was weakened
      when forced choice or brief durations were used. We here describe measurements of
      the gap effect in the parafovea. The stimuli were 1 deg of visual angle in width
      and were centered on an imaginary circle of radius 5 deg. They were brief (100
      ms), and thresholds were measured with a spatial two-alternative forced choice.
      Under these conditions we find a clear gap effect, which is of similar magnitude
      for both the cardinal chromatic axes. It may be a chromatic analog of the
      crowding effect observed for parafoveal perception of form.

PMID- 16961989
TI  - Do rods influence the hue of foveal stimuli?
AB  - To understand the generality and mechanisms of previously reported rod hue
      biases, we examined whether they are present for small foveal stimuli by
      comparing the wavelengths of the three spectral unique hues under dark-adapted
      and flash-bleached conditions. Rod green bias (shift of unique yellow) and rod
      blue bias (shift of unique green) were found for some observers with 1 degrees 
      diameter foveal stimuli, the size most likely to stimulate rods. Smaller stimuli
      (0.2 degrees and 0.6 degrees diameter), which were least likely to stimulate
      rods, produced no large or consistent differences between dark-adapted and
      bleached conditions. This suggests that rod hue biases result from the local
      stimulation of rods by light, not from remote suppression by dark-adapted,
      unstimulated rods, and not from bleaching light artifacts.

PMID- 16961990
TI  - The color of night: Surface color perception under dim illuminations.
AB  - Several studies document rudimentary color vision under dim illumination. Here,
      hue perceptions of paper color samples were determined for a wide range of light
      levels, including very low light levels where rods alone mediate vision. The
      appearances of 24 paper color samples from the OSA Uniform Color Scales were
      gauged under successively dimmer illuminations from 10-0.0003 Lux. Triads of
      samples were chosen representing each of eight basic color categories; red, pink,
      orange, yellow, green, blue, purple, and gray. Samples within each triad varied
      in lightness. Observers sorted samples into groups that they could categorize
      with specific color names. Above 0.32 Lux, observers sorted the samples into the
      originally chosen color groups with few exceptions. For 0.1-0.01 Lux, the red and
      orange samples were usually correctly identified as either red or orange. The
      remaining samples tended to be grouped into two categories, associated with the
      scotopic sample reflectance. The lowest reflectance samples were below threshold
      and were named black. The higher reflectance group was named predominately as
      green or blue-green (three observers; the fourth observer used blue or
      achromatic). At the three dimmest levels (< or = 0.0032 Lux) there continued to
      be conspicuous color percepts. Color categories were reliably assigned based on
      relative sample scotopic lightness. Of the samples above threshold, those with
      lower reflectance were classified as red or orange (all observers) and the higher
      reflectance samples as green or blue-green (three observers) or achromatic or
      blue (the fourth observer). Rods and L-cones presumably mediated color percepts
      at the intermediate light levels used in the study. At the three lowest light
      levels there were distinct color appearances mediated exclusively by rods. We
      speculate that at these light levels the visual system estimates probable colors
      based on prior natural experience.

PMID- 16961991
TI  - Dark-adapted rod suppression of cone flicker detection: Evaluation of receptoral
      and postreceptoral interactions.
AB  - Dark-adapted rods in the area surrounding a luminance-modulated field can
      suppress flicker detection. However, the characteristics of the interaction
      between rods and each of the cone types are unclear. To address this issue, the
      effect that dark-adapted rods have on specific classes of receptoral and
      postreceptoral signals was determined by measuring the critical fusion
      frequencies (CFF) for receptoral L-, M-, and S-cone and postreceptoral luminance
      ([L+M+S] and [L+M+S+Rod]) and chromatic ([L/(L+M)]) signals in the presence of
      different levels of surrounding rod activity. Stimuli were generated with a two
      channel photostimulator that has four primaries for a central field and four
      primaries for the surround, allowing independent control of rod and cone
      excitation. Measurements were made either with adaptation to the stimulus field
      after dark adaptation or during a brief period following light adaptation. The
      results show that dark-adapted rods maximally suppressed the CFF by approximately
      6 Hz for L-cone, M-cone, and luminance modulation. Dark-adapted rods, however,
      did not significantly alter the S-cone CFF. The [L/(L+M)] postreceptoral CFF was
      slightly suppressed at higher surround illuminances, that is, higher than
      surround luminances resulting in suppression for L-cone, M-cone, or luminance
      modulation. We conclude that rod-cone interactions in flicker detection occurred
      strongly in the magnocellular pathway.

PMID- 16961992
TI  - Foveal and extra-foveal influences on rod hue biases.
AB  - Green, blue and short-wavelength-red rod hue biases are strongest and most
      reliable with large, dimly-mesopic, extra-foveal stimuli but tend to diminish
      when stimuli are confined to a small area of the central fovea. This study
      explores how the stimulation of foveal and extra-foveal areas interact in
      determining rod hue biases, and whether large stimuli are as effective for
      revealing rod hue biases when foveally centered as when eccentrically centered.
      We assessed rod influence by measuring wavelengths of unique green and unique
      yellow (with 1-s duration, 1 log scot td stimuli and a staircase procedure) under
      bleached and dark-adapted conditions. We measured unique hues with foveally
      centered 2 degrees - and 7.4 degrees -diameter disks, a 7.4 degrees (outer) x 2
      degrees (inner) diameter annulus, and a 7 degrees -eccentric, 7.4 degrees 
      diameter disk. The rod green bias (shift of unique yellow locus) was typically
      <10 nm and remained fairly constant across spatial configurations, indicating no
      special foveal influence. The rod blue bias (shift of unique green) varied more
      among observers and spatial configurations, reaching up to 47 nm. However,
      stimuli covering the fovea typically produced no rod blue bias. Thus, the present
      results add differences in spatial dependence (i.e., foveal/extra-foveal
      interaction) between green and blue rod biases to previously demonstrated
      differences (e.g., differences in amount of light level dependence, in time
      course and in the spectral range influenced by each bias).

PMID- 16961993
TI  - Cone contrasts do not predict color constancy.
AB  - A successive, asymmetric color-matching paradigm was used to investigate the link
      between cone contrast and the stability of perceived colors. We measured the
      perceived color shifts of 10 Munsell samples, induced by test illuminant A,
      simulated in u'v' color space. The capacity of the visual system to resist these
      shifts, otherwise known as color constancy, is measured in terms of the Brunswik
      ratio, BR. Cone contrasts are calculated with respect to either the physical or
      perceived background. Subjective cone contrasts show a better fit to the von
      Kries law than those based on the physical background. Complete cone adaptation
      occurs when color constancy is high. However we show conditions where cone
      adaptation seems complete but color constancy is poor.

PMID- 16961994
TI  - Macular pigment and color discrimination.
AB  - An earlier modeling study of the effect of changes in macular pigment optical
      density (MPOD) on a wide range of surface colors is re-examined. That study
      reported changes in local chromaticity variance and in color spacing, some of
      which were incompatible with tritan-like confusions in normals associated with
      high-simulated MPOD. This disagreement might have arisen through the use of the
      von Kries correction for adaptation. The analysis is repeated, using 1782
      reflectance spectra of natural and man-made colors. These colors are segregated
      into an array of 25 equally populated cells in an analogue of the MacLeod-Boynton
      cone excitation diagram. Removing the von Kries correction restores compatibility
      with other experimental data. Differences between the results for normal and
      anomalous trichromats, noted in the earlier study, are confirmed. An analysis of
      local chromaticity variance across color space indicates the presence of
      systematic patterns. The earlier study also reported differences in results
      across observer types (for example, between normals and protanomals) and this is
      addressed here by utilizing fundamentals defined by a variable photopigment
      template. Chromaticities are computed for the same 1782 reflectance spectra for
      normals and for a set of protanomals (for whom the anomalous L pigment is shifted
      between the normal L and M spectral locations). Colors are segregated into an
      array of 100 cells in an analogue of the MacLeod-Boynton cone excitation diagram.
      Changes in chromaticity variance with MPOD for these cells are mapped for normals
      and protanomals. Variance along the L/(L + M) axis is sensitive to the number of
      cells used for segmentation. It also increases with MPOD for normal observers but
      this trend reverses as the wavelength of maximum sensitivity of the L cone shifts
      towards shorter wavelengths (protanomalous locations).

PMID- 16961995
TI  - Visual sensitivity to color errors in images of natural scenes.
AB  - Simple color-difference formulae and pictorial images have traditionally been
      used to estimate the visual impact of color errors introduced by image
      reproduction processes. But the limited gamut of RGB cameras constrains such
      analyses, particularly of natural scenes. The purpose of this work was to
      estimate visual sensitivity to color errors introduced deliberately into pictures
      synthesized from hyperspectral images of natural scenes without gamut constraints
      and to compare discrimination thresholds expressed in CIELAB and S-CIELAB color
      spaces. From each original image, a set of approximate images with variable color
      errors were generated and displayed on a calibrated RGB color monitor. The
      threshold for perceptibility of the errors was determined in a paired-comparison
      experiment. In agreement with previous studies, it was found that discrimination
      between original and approximate images needed on average a CIELAB color
      difference DeltaEab* of about 2.2. Although a large variation of performance
      across the nine images tested was found when errors were expressed in CIELAB
      units, little variation was obtained when they were expressed in S-CIELAB units.

PMID- 16961996
TI  - Resolution of binocular rivalry: Perceptual misbinding of color.
AB  - Is neural binding of color and form required for perception of a unified colored
      object? Individual cells selectively tuned to both color and orientation are
      proposed to moot the binding problem. This study reveals perceptual misbinding of
      color, thereby revealing separate neural representations of color and form
      followed by a subsequent binding process. Low luminance-contrast, rivalrous
      chromatic gratings were presented dichoptically. Each grating had alternating
      chromatic and gray stripes (e.g., red/gray in the left eye, green/gray in the
      right eye). Observers viewed the two rivalrous, 2 cpd gratings for 1 min. The
      duration of exclusive visibility was measured for four percepts: left-eye
      stimulus, right-eye stimulus, fusion of the two colors, or a two-color grating
      (e.g. a red/green grating). The percept of a two-color grating (misbinding) was
      observed with Michelson luminance contrast in the grating up to 20%. In general,
      for a given level of luminance contrast either misbinding (low luminance
      contrast) or color mixture (high luminance contrast) was observed, but not both
      of them. The perceived two-color gratings show that two rivalrous chromaticities
      are both represented neurally when color and form are combined to give a unified
      percept. "Resolution" of competing chromatic signals from the two eyes is not
      restricted to color dominance and color mixture. The transition from misbinding
      to color mixture by increasing luminance contrast shows that luminance edges have
      an important role in correct localization of color.

PMID- 16961997
TI  - Color shifts induced by S-cone patterns are mediated by a neural representation
      driven by multiple cone types.
AB  - This study investigated chromatic induction from inhomogeneous background
      patterns. Previous work showed that a background pattern detected by only S cones
      induced strong color shifts in a nearby test area (Monnier & Shevell, 2003). In
      that work, the S-cone patterns were composed with constant L- and M-cone
      stimulation over the entire background; in terms of L and M cones, therefore, the
      background was uniform. S-cone stimulation was varied over space to produce S
      cone-isolated background patterns. These S-cone patterns, however, established
      spatial structure (the pattern) at both the receptoral level (S-cone stimulation)
      and the postreceptoral level (S/(L+M)). Here, these two levels of pattern
      representation were unconfounded to determine whether color shifts induced by S
      cone patterns were due to spatial structure within an S-cone-specific neural
      pathway versus a pathway that combines responses from S cones and other cone
      types (e.g. S/(L+M)). The results showed that the induced color shifts were
      mediated by signals within a pathway that combines responses from multiple cone
      types. These results are consistent with a +s/-s spatially antagonistic neural
      receptive field, which is found in some neurons in V1 and V2.

PMID- 16961998
TI  - Spatial profile of contours inducing long-range color assimilation.
AB  - Color induction was measured using a matching method for two spatial patterns,
      each composed of double contours. In one pattern (the standard), the contours had
      sharp edges to induce the Watercolor Effect (WCE); in the other, the two contours
      had a spatial taper so that the overall profile produced a sawtooth edge, or
      ramped stimulus. These patterns were chosen based on our previous study
      demonstrating that the strength of the chromatic WCE depends on a luminance
      difference between the two contours. Low-pass chromatic mechanisms, unlike
      bandpass luminance mechanisms, may be expected to be insensitive to the
      difference between the two spatial profiles. The strength of the watercolor
      spreading was similar for the two patterns at narrow widths of the contour
      possibly because of chromatic aberration, but with wider contours, the standard
      stimulus produced stronger assimilation than the ramped stimulus. This research
      suggests that luminance-dependent chromatic mechanisms mediate the WCE and that
      these mechanisms are sensitive to differences in the two spatial profiles of the
      pattern contours only when they are wide.

PMID- 16961999
TI  - A whiter shade of pale, a blacker shade of dark: Parameters of spatially induced
      blackness.
AB  - The surface-mode property of "blackness" is induced by simultaneous contrast with
      an adjacent, more luminant surround. As numerous studies have shown, the degree
      of blackness induced within an achromatic test field is a function of the
      relative luminance of the adjacent chromatic inducing field, but not of its hue.
      But in the converse case of chromatic test fields, susceptibility to blackening
      has been reported to vary with wavelength. The present study investigates this
      possibility, that some wavelengths are more susceptible. We also questioned
      whether "white" and "black" sensory components function as opposites in blackness
      appearance. We recorded the appearance of a central monochromatic test field of
      constant luminance (10 cd/m2), with wavelength ranging across the visible
      spectrum, while a broadband white annulus was set to six luminance levels ranging
      across three log steps. Three color-normal observers followed a color-naming
      technique. All six opponent-hue names and their combinations were response
      options; blackness and whiteness in the test field could therefore be reported
      independently. Of primary interest were the achromatic responses. When
      represented within a multidimensional space, these revealed the "white-to-black"
      dimension but in addition a quality (dimension) of "desaturation." Compared
      against chromatic properties of the test field, the results provide evidence that
      blackness is a function of inducing field brightness (not luminance). This result
      is in accord with observations made by Shinomori et al. (1997) using a different
      procedure. We conclude that blackness induction occurs at a stage of visual
      processing subsequent to the origin of the brightness signal from a combination
      of opponent-process channels.

PMID- 16962000
TI  - The discoloration illusion.
AB  - The discoloration illusion, a new visual phenomenon, is described. This
      phenomenon originates from the juxtaposition of eight chromatic parallel contours
      on a white background, creating a luminance gradient and enclosing a light red
      region. Under these conditions, the inner region appears white: the light red
      discolors and appears white with both surface color and luminous qualities. In
      two experiments, the discoloration illusion was (i) compared with the coloration
      effect of the watercolor illusion, obtained when the number of adjacent contours
      was reduced to at least two, and (ii) tested under several conditions useful for
      understanding the roles of the luminance gradient profile. The results suggest
      that discoloration is not a lightness illusion and does not depend on
      simultaneous contrast or on achromatic mechanisms, but more likely on chromatic
      mechanisms that, through the luminance chromatic gradient, provide cues about the
      interactions of light and surface and model the volume by depicting lights and
      shades. The discoloration illusion suggests a possible neural scenario where
      multiple juxtaposed contours may stimulate neurons, selective for different
      asymmetric luminance profiles and signaling not only the unilateral belongingness
      of the boundaries and the coloration effect but also the volumetric and the
      illumination effects.

PMID- 16962001
TI  - Effects of motion and configural complexity on color transparency perception.
AB  - We tested whether motion and configural complexity affect perceived transparency.
      A series of five coherent chromatic transformations in color space was applied
      across a figure: translation, convergence, shear, divergence and rotation. The
      stimuli consisted of a bipartite or a checkerboard configuration (10 x 10
      degrees), with a central static or moving overlay (5 x 5 degrees). Three
      different luminance conditions (the plane of chromatic transformation oriented
      toward higher, lower, or equal luminances) were also tested for each of three
      modulation depths. For each stimulus, the observer judged whether the overlay
      appeared transparent or not. The main results indicated an interaction between
      the type of chromatic transformation and stimulus motion and complexity. For
      example, convergences are judged to appear transparent significantly more often
      when motion is added for bipartite configurations, or when they are generated in
      a checkerboard configuration. Surprisingly, shears that have been reported to
      appear opaque, are more frequently reported to appear transparent with short
      vector lengths and when combined with motion. Other transformations are also
      affected by motion, although the effectiveness of figural complexity on
      transparency seems to depend on both the type of color shifts and the presence of
      motion. The results indicate that adding motion and stimulus complexity are not
      necessarily neutral with respect to the chromatic shifts evoking transparency.
      Thus, studies that have used motion to enhance transparency may yield different
      results about the color shifts supporting transparency perception from those that
      did not. The same might be supposed for stimulus complexity under some
      conditions.

PMID- 16962002
TI  - Color stimuli perception in presence of light scattering.
AB  - Perception of different color contrast stimuli was studied in the presence of
      light scattering: in a fog chamber in Clermont-Ferrand and in laboratory
      conditions where light scattering of similar levels was obtained, using different
      light scattering eye occluders. Blue (shortest wavelength) light is scattered in
      fog to the greatest extent, causing deterioration of vision quality especially
      for the monochromatic blue stimuli. However, for the color stimuli presented on a
      white background, visual acuity in fog for blue Landolt-C optotypes was higher
      than for red and green optotypes on the white background. The luminance of color
      Landolt-C optotypes presented on a LCD screen was chosen corresponding to the
      blue, green, and red color contributions in achromatic white stimuli (computer
      digital R, G, or B values for chromatic stimuli equal to RGB values in the
      achromatic white background) that results in the greatest luminance contrast for
      the white-blue stimuli, thus advancing the visual acuity for the white-blue
      stimuli. Besides such blue stimuli on the white background are displayed with a
      uniform, spatially unmodulated distribution of the screen blue phosphor emission
      over the entire area of the screen including the stimulus C optotype area. It
      follows that scattering, which has the greatest effect on the blue component of
      screen luminance, has the least effect on the perception of white-blue stimuli.

PMID- 16962003
TI  - Color scaling of discs and natural objects at different luminance levels.
AB  - Assigning a basic color name to an object and rating the amount of a particular
      hue is a fundamental visual capability. Traditional color scaling studies have
      used increment flashes or isoluminant stimuli of a homogeneous color. Natural
      objects, however, do not contain a single color but are characterized by a
      distribution of different chromatic hues. Here we study color scaling using
      photographs of natural fruit objects. Stimuli were either homogeneous spots,
      digital photographs of fruit objects (e.g., banana), or outline shapes of the
      fruit objects. Stimuli were displayed on a CRT monitor on a homogeneous white
      background; its luminance was varied above and below the medium gray. The
      chromaticity of the stimuli was varied in 36 equally spaced chromatic directions
      in the isoluminant plane of the Derrington-Krauskopf-Lennie (DKL) color space.
      For each stimuli, subjects rated the amount of red, green, blue, and yellow in
      the stimulus on a scale from 0-8. In agreement with earlier studies we found that
      the positions of the peak ratings for each color do not coincide with the
      cardinal axis of DKL color space and are largely invariant under changes of the
      background luminance. For the average rating we found a dependence on background
      luminance for all colors: yellow ratings increase with darker backgrounds,
      whereas ratings for the other colors, in particular green, decrease. For the
      fruit objects, we found a selective increase in the average color rating for the
      natural fruit color. For example, the average rating for yellow was 1.7 times
      higher for the banana images compared to disc stimuli. No such selective increase
      was found for outline shapes. We conclude that the distribution of hues in
      natural objects with a characteristic object color can have a profound effect on
      color scaling and color appearance.

PMID- 16962004
TI  - Achromatic parvocellular contrast gain in normal and color defective observers:
      Implications for the evolution of color vision.
AB  - The PC pathway conveys both chromatic and achromatic information, with PC neurons
      being more responsive to chromatic (L-M) than to achromatic (L+M) stimuli. In
      considering the evolution of color vision, it has been suggested that the dynamic
      range of chromatic PC-pathway processing is tuned to the chromatic content of the
      natural environment. Anomalous trichromats, with reduced separation of their L-
      and M-cone spectral sensitivities, have diminished chromatic input to PC-pathway
      cells. Dichromats, with absent L or M cones, should have no chromatic input to PC
      pathway cells. Therefore, the PC-pathway dynamic range of color defectives should
      be released from any constraint imposed by the chromatic environment. Here we ask
      whether this results in compensatory enhancement of achromatic PC-pathway
      processing in color defectives. This study employed a psychophysical method
      designed to isolate PC-pathway processing using achromatic stimuli. In a pulsed
      pedestal condition, a four-square stimulus array appeared within a uniform
      surround. During a trial, one of the test squares differed from the other three,
      and the observer's task was to choose the square that was different. A four
      alternative, forced-choice method was used to determine thresholds as a function
      of the contrast of the four-square array to the surround. Seven color defective
      and four normal observers participated. Results showed no systematic differences
      between normals and color defectives. There was no enhancement of achromatic
      processing as compensation for reduced chromatic processing in the PC-pathway
      system in color defectives. From physiological recordings, PC-pathway achromatic
      contrast gains of dichromatic and trichromatic New World primates and
      trichromatic Old World macaques have also been shown to be similar to each other.
      Our study and the animal studies imply that PC-pathway contrast gain parameters
      were regulated by factors other than the environmental chromaticity gamut, and
      may have arisen in a nontrichromatic common ancestor to both Old and New World
      primates.

PMID- 16962005
TI  - Normal and dichromatic color discrimination measured with transient visual evoked
      potential.
AB  - It would be informative to have an electrophysiological method to study, in an
      objective way, the effects of mercury exposure and other neurotoxics on human
      color vision performance. The purpose of the present work was to study human
      color discrimination by measuring chromatic difference thresholds with visual
      evoked potential (VEP). Six young normal trichromats (24 +/- 1 years old) and one
      deutan (26 years old) were tested. The stimuli consisted of sinusoidal
      isoluminant chromatic gratings made from chromaticity pairs located along four
      different color directions centered on two reference points. Heterochromatic
      flicker photometry (HFP) protocol was used to obtain the isoluminance condition
      for every subject and for all chromaticity pairs. Spatial frequency was 2
      cycles/deg. Presentation mode comprised onset (300 ms)/offset (700 ms) periods.
      As previously described, we found a negative deflection in the VEP which was
      related to the chromatic difference: as chromatic difference increased, amplitude
      increased and latency decreased. VEP response amplitude was plotted against
      distance in the CIE 1976 color space between the grating chromaticities and
      fitted with a regression line. We found color thresholds by extrapolating the
      fitting to null amplitude values. The thresholds were plotted in the CIE 1976
      color space as MacAdam ellipses. In normal trichromats the ellipses had small
      size, low ellipticity, and were vertically oriented. In the deutan subject, the
      ellipses had large size, high ellipticity, and were oriented towards the deutan
      copunctal locus. The VEP thresholds were similar to those obtained using grating
      stimuli and psychophysical procedures, however smaller than those obtained using
      pseudoisochromatic stimuli (Mollon-Reffin method). We concluded that transient
      VEP amplitude as a function of contrast can be reliably used in objective studies
      of chromatic discrimination performance in normal and altered human subjects.

PMID- 16962006
TI  - Anomalous trichromats' judgments of surface color in natural scenes under
      different daylights.
AB  - Deuteranomalous trichromacy, which affects medium-wavelength-sensitive cones, is
      more common than protanomalous trichromacy, which affects long-wavelength
      sensitive cones. The aim of the present work was to test the extent to which
      these two kinds of anomalous trichromacy affect surface-color judgments in the
      natural world. Simulations of 18 natural scenes under different daylight
      illuminants were presented on a high-resolution color monitor to 7
      deuteranomalous, 7 protanomalous, and 12 normal trichromatic observers, who had
      to discriminate between reflectance and illuminant changes in the images.
      Observers' ability to judge surface color was quantified by a standard color
      constancy index. Deuteranomalous trichromats performed as well as normal
      trichromats, but protanomalous trichromats performed more poorly than both. The
      results are considered in relation to the spectral coverage of cones, rod
      intrusion, and the characterization of anomalous trichromacy by the Rayleigh
      match.

PMID- 16962007
TI  - Color naming and categorization in inherited color vision deficiencies.
AB  - Dichromatic subjects can name colors accurately, even though they cannot
      discriminate among red-green hues (Jameson & Hurvich, 1978). This result is
      attributed to a normative language system that dichromatic observers developed by
      learning subtle visual cues to compensate for their impoverished color system.
      The present study used multidimensional scaling techniques to compare color
      categorization spaces of color-vision deficient (CVD) subjects to those of normal
      trichromat (NT) subjects, and consensus analysis estimated the normative effect
      of language on categorization. Subjects sorted 140 Munsell color samples in three
      different ways: a free sorting task (unlimited number of categories), a
      constrained sorting task (number of categories limited to eight), and a
      constrained naming task (limited to eight basic color terms). CVD color
      categories were comparable to those of NT subjects. For both CVD and NT subjects,
      a common color categorization space derived from the three tasks was well
      described by a three-dimensional model, with the first two dimensions
      corresponding to reddish-greenish and yellowish-bluish axes. However, the third
      axis, which was associated with an achromatic dimension in NTs, was not
      identified in the CVD model. Individual differences multidimensional scaling
      failed to reveal group differences in the sorting tasks. In contrast, the
      personal color naming spaces of CVD subjects exhibited a relative compression of
      the yellowish-bluish dimension that is inconsistent with the typical deutan-type
      color spaces derived from more direct measures of perceptual color judgments. As
      expected, the highest consensus among CVDs (77%) and NTs (82%) occurred in the
      naming task. The categorization behaviors studied in this experiment seemed to
      rely more on learning factors, and may reveal little about CVD perceptual
      representation of colors.

PMID- 16962008
TI  - Psychophysical assessment of magno- and parvocellular function in schizophrenia.
AB  - Recently developed psychophysical techniques permit the biasing of the processing
      of the stimulus by early visual channels so that responses reflect
      characteristics of either magno- or parvocellular pathways (Pokorny & Smith,
      1997). We used such techniques to test psychophysically whether the global
      magnocellular dysfunction reported in schizophrenia also affects early processes.
      Seven schizophrenic patients and 19 normal controls participated. The task was a
      four-alternative forced-choice luminance discrimination, using a 2 x 2
      configuration of four 1-deg squares. Target luminance threshold was determined in
      three conditions: the stimulus, including the target, was pulsed for 17 ms (pulse
      paradigm); the target was presented on a steady background of four squares
      (steady paradigm), or the target was presented alone (no background paradigm). We
      replicated previous results demonstrating magnocellular and parvocellular
      signatures in control participants. No evidence for an early magnocellular
      deficit could be detected as the thresholds of all schizophrenic observers were
      higher both in the steady paradigm (presumed magnocellular mediation) and in the
      pulse paradigm (presumed parvocellular mediation). Magnocellular dysfunction, if
      present in schizophrenia, must concern more integrated processes, possibly at
      levels at which parvocellular and magnocellular paths interact.

PMID- 16962009
TI  - Hyperoxia, hyperglycemia, and photoreceptor sensitivity in normal and diabetic
      subjects.
AB  - The aim of this study was to investigate the effects of an increase in the
      saturation of blood oxygen (SaO2) and/or serum glucose on photoreceptor
      sensitivity in normal subjects and in patients with diabetes mellitus. We
      monitored cone and rod sensitivity by recording dark-adaptation curves to both
      green and red test stimuli while inhaling either air (20% O2 + 80% N2) or 100%
      oxygen in 12 normal subjects and 12 diabetic patients with no (10) or mild (2)
      retinopathy. We also repeated the experiment in 10 of the normal subjects under
      hyperglycemia (mean serum glucose: 161 mg/dl). Results show that in normal
      subjects the dark-adapted cone sensitivity is improved by an increase in SaO2 or
      by hyperglycemia. Final rod sensitivity is unchanged during hyperoxia and during
      hyperglycemia when measured with a green test spot. However the kinetics of dark
      adaptation are altered during hyperglycemia, and an increase in final sensitivity
      is observed when measured with the red test spot. Inhalation of oxygen during
      hyperglycemia in normal subjects reduces cone sensitivity compared to that found
      during hyperglycemia alone (Pasteur effect). In diabetic subjects the dark
      adapted cone threshold is comparable to that found in normal subjects, and
      sensitivity also increases with an increase in SaO2. The final rod threshold,
      however, is impaired compared to that of the control group, and rod sensitivity
      is improved by increasing the SaO2. The results suggest that the metabolism of
      rods and cones may differ in normal subjects: in cones, the rate of metabolism
      can be augmented by increasing the available oxygen or glucose, whereas rods
      appear more insensitive to increased blood oxygen saturation and hyperglycemia.
      In diabetic subjects, both cone and rod metabolism can be increased by
      supplemental oxygen, indicative of an early rod deficit. The study lends weight
      to the hypothesis that dark-adapted rods in diabetics are hypoxic before the
      onset of retinopathy.

PMID- 16962010
TI  - Color space distortions in patients with type 2 diabetes mellitus.
AB  - Color vision impairment was examined in patients with type 2 diabetes mellitus
      (DM2) without retinopathy. We assessed the type and degree of distortions of
      individual color spaces. DM2 patients (n = 32), and age-matched controls (n = 20)
      were tested using the Farnsworth D-15 and the Lanthony D-15d tests. In addition,
      subsets of caps from both tests were employed in a triadic procedure (Bimler &
      Kirkland, 2004). Matrices of inter-cap subjective dissimilarities were estimated
      from each subject's "odd-one-out" choices, and processed using non-metric
      multidimensional scaling. Two-dimensional color spaces, individual and group (DM2
      patients; controls), were reconstructed, with the axes interpreted as the R/G and
      B/Y perceptual opponent systems. Compared to controls, patient results were not
      significant for the D-15 and D-15d. In contrast, in the triadic procedure the
      residual distances were significantly different compared to controls: right eye,
      P = 0.021, and left eye, P = 0.022. Color space configurations for the DM2
      patients were compressed along the B/Y and R/G dimensions. The present findings
      agree with earlier studies demonstrating diffuse losses in early stages of DM2.
      The proposed method of testing uses color spaces to represent discrimination and
      provides more differentiated quantitative diagnosis, which may be interpreted as
      the perceptual color system affected. In addition, it enables the detection of
      very mild color vision impairment that is not captured by the D-15d test. Along
      with fundoscopy, individual color spaces may serve for monitoring early
      functional changes and thereby to support a treatment strategy.

PMID- 16962011
TI  - Psychophysical estimation of the best illumination for appreciation of
      Renaissance paintings.
AB  - A variety of light sources are used in museum environments where the main concern
      is to prevent damaging effects of the light on paintings. Yet, the visual
      impression of an artistic painting is strongly influenced by the intensity and
      spectral profile of the illumination. The aim of this work was to determine
      psychophysically the spectral profile of the illumination preferred by observers
      when seeing paintings dated from the Renaissance epoque and to investigate how
      their preferences correlate with the color temperature of the illumination and
      with the chromatic diversity of the paintings. Hyperspectral images of five oil
      paintings on wood were collected at the museum and the appearance of the
      paintings under five representative illuminants computed. Chromatic diversity was
      estimated by computing the representation of the paintings in the CIELAB color
      space and by counting the number of nonempty unit cubes occupied by the
      corresponding color volume. A paired-comparison experiment using precise cathode
      ray tube (CRT) reproductions of the paintings rendered with several illuminant
      pairs with different color temperatures was carried out to determine observers'
      preference. The illuminant with higher color temperature was always preferred
      except for one pair where no clear preference was expressed. The preferred
      illuminant produced the larger chromatic diversity, and for the condition where
      no specific illuminant was preferred the number of colors produced by the
      illuminant pair was very similar, a result suggesting that preference could have
      been influenced by chromatic diversity.

PMID- 16962012
TI  - The effect of test distance on the CN lantern results.
AB  - The purpose of this study is to determine how the viewing distance affects the
      pass/fail results of the CN Lantern (CNLan). The CNLan is a color vision test
      designed for the railway industry. It presents 15 triplets of colored lights that
      could be any combination of red, green and yellow. The test was viewed from 4.6 m
      and 2.3 m. Sixty-seven color-defectives participated in the first part of the
      study. Sixty-six percent of the subjects repeated the experiment 10 days later.
      There was a significant (P < 0.05) decrease in the mean number of errors from 7.6
      to 4.3 as the distance decreased. There was also a corresponding increase in the
      percentage of subjects who passed from 9.0% at 4.6 m to 20.9% at the 2.3 m
      viewing distance. None of the subjects who passed at the longer distance failed
      at the shorter distance. The replication results were statistically identical to
      the first session (P > 0.05). Decreasing the CNLan viewing distance by 50% does
      decrease the number of errors and increase the pass rate. This indicates that
      some color-defectives could work in the railway yards where the sighting
      distances for the signal lights are shorter than on the main track.

PMID- 16962013
TI  - Color changes in the red-green plates of the 50-year-old AO HRR color vision
      test.
AB  - The original AO HRR color vision test has been considered by many as one of the
      best plate tests. It is still accepted by many governmental agencies for color
      vision certification. In their 1954 publication, Hardy, Rand, and Rittler stated
      that specially compounded inks were used for printing to avoid color changes with
      time. Fifty years later, it is both important and interesting to determine
      whether the wear and tear cause significant color changes. The chance finding of
      a never-used second edition offers an opportunity to evaluate the color changes.
      A GretagMacbeth Spectrolino spectrophotometer was used to measure the
      chromaticities of the never-used book, and an extensively used book. Four plates
      (#4, 7, 13, 16), selected randomly from the four red-green sections, were
      analyzed. The colored dots from each of the eight plates were plotted on a CIE
      chromaticity diagram. Isocolor lines were drawn to evaluate chromatic alignment.
      Chromaticities for plates #4 and 7 are significantly different between the two
      books. With regard to alignment with isocolor lines, the extensively used book is
      better than the never-used book for plate #4. There is significant misalignment
      on plate #7 for both books. Chromaticities for plates #13 and 16 are essentially
      identical between books, all with good alignment with isocolor lines. The overall
      comparison shows that the chromatic alignment characteristics of the extensively
      used book are not worse than the never-used book. Since colors in these plates
      have to be aligned with both the protan and deutan axes, any significant color
      changes would have disturbed this delicate requirement. The findings of many
      plates with good alignment, and the lack of differences on plates #13 and 16
      between books, suggest that there are no significant color changes over time.
      Differences between books on plates #4 and 7 were likely the result of the
      original printing process.

PMID- 16962014
TI  - An adaptation of the Cambridge Colour Test for use with animals.
AB  - Recently, molecular biological techniques have presented new opportunities for
      addressing questions concerning the neural mechanisms involved in color coding,
      thereby rousing renewed interest in animal color vision testing. We have modified
      a computer-based assessment tool, the Cambridge Colour Test, to make it suitable
      for use with animals. Here, the validity and reliability of the testing method
      were evaluated using squirrel monkeys. Because the chromatic stimuli and the
      achromatic backgrounds of the test consist of dots that vary in lightness, the
      stimulus parameters can be adjusted so that animals are not able to use luminance
      differences to make correct discriminations. Thus, in contrast to methods used
      previously, this test does not require that time be spent equating the luminance
      of each chromatic stimulus examined. Furthermore, the computer video-display
      based design of the testing apparatus can be easily replicated and adapted for
      use with many species in a variety of settings. In the present experiments, the
      squirrel monkeys' behavioral results agreed with the predictions for their color
      vision based on genetic analysis and electroretinography (ERG) spectral
      sensitivity data. Repeated measurements were highly consistent. Thus, an
      adaptation of the Cambridge Colour Test provides a valid and reliable method for
      testing color vision in animals.

PMID- 16962015
TI  - Normotonic cell shrinkage induced by Na+ deprivation results in apoptotic cell
      death in human epithelial HeLa cells.
AB  - Apoptosis is a major form of cell death that occurs in response to a variety of
      signals in both physiological and pathological situations. A hallmark of
      apoptosis is normotonic cell shrinkage, called apoptotic volume decrease (AVD),
      the process of which involves fluxes of K(+), Cl(-), and Na(+). Na(+) influx was
      suggested to be required in Fas-induced apoptosis in human Jurkat T cells,
      whereas Na(+) efflux was found to be associated with AVD and apoptosis in human
      HL-60 cells. Here we examined the effects of extracellular Na(+) deprivation on
      cell volume and viability in human epithelial HeLa cells. The incubation of HeLa
      cells in normotonic Na(+)-free Ringer solution resulted in persistent cell
      shrinkage after > or = 30 min and reduction in cell viability after > or = 1 h.
      After exposure to Na(+)-free solution for 5 h, a marked reduction in cell
      viability was found to be associated with an activation of caspase-3 without
      showing significant LDH release, indicating that the cells underwent apoptosis
      but not necrosis. Na(+) deprivation-induced cell shrinkage and apoptotic cell
      death were significantly inhibited by a blocker of Na(+)-K(+)-2Cl(-)
      cotransporter (NKCC) or of the reverse-mode operation of Na(+)/Ca(2+) exchanger
      (NCX), but not by a blocker of Na(+)/H(+) exchanger (NHE). Therefore it is
      concluded that Na(+) deprivation causes persistent cell shrinkage resulting from
      Na(+) efflux mainly via NKCC and NCX and thereafter leads to apoptotic death of
      HeLa cells. It is also suggested that normotonic cell shrinkage per se, if
      persistent, provides a sufficient condition for apoptosis induction.

PMID- 16962016
TI  - Lichen amyloidosis of the auricular concha: report of two cases and review of the
      literature.
AB  - Two cases of lichen amyloidosis of the auricular concha are presented here,
      supplementing the already approximately twenty cases of lichen amyloidosis of the
      auricular concha reported to date. The first patient is a 60-year-old woman who
      presented with a 4-year history of an itchy rash that started in the bowl of her
      left ear, and soon after appeared on the right side as well. The second patient
      is a 44-year-old woman who presented with a long-standing pruritic rash on her
      upper back. This had become noticeably darker over the past several years. In one
      of the two cases lichen amyloidosis of the auricular concha reported here,
      concomitant macular amyloidosis of the back was present. Combined cases of lichen
      and macular amyloidosis are termed biphasic amyloidosis, and provide support to
      the theory that these two variants of amyloidosis exist on the same disease
      spectrum.

PMID- 16962017
TI  - Fibroepithelioma of pinkus.
AB  - An 88-year-old woman presented with an 8-year history of a slowly enlarging
      growth on the suprapubic area. A shave excision of this lesion demonstrated
      fibroepithelioma of Pinkus (FEP). Fibroepithelioma of Pinkus is an indolent
      growing tumor that traditionally has been classified as a variant of the basal
      cell carcinoma. More recent evidence favors the classification of FEP as a
      variant of trichoblastoma. In this case report, we identified a large FEP with
      benign histologic features suggestive of a follicular origin as demonstrated in
      part by CK 20 staining and the presence of scattered Merkel cells within the
      tumor. The pathogenesis of FEP remains enigmatic, and the genetic basis has yet
      to be fully elucidated. Complete surgical resection is considered curative.

PMID- 16962018
TI  - Zosteriform lichen planus.
AB  - A 95-year-old woman presented with a 4-month history of a pruritic eruption
      involving her trunk, medial thighs, and lesions limited to the C5 dermatome of
      the left upper extremity. Punch biopsy supported a clinical diagnosis of
      zosteriform lichen planus. Linear lichen planus refers to lichen planus with a
      unilateral linear distribution. This variant may present as an example of the
      Wolf isotopic response, or more rarely, a de novo eruption on previously-normal
      skin. In very rare instances linear lichen planus presents in a segmental fashion
      corresponding to a dermatome and is termed zosteriform lichen planus.

PMID- 16962019
TI  - Muir-Torre syndrome.
AB  - A 65-year-old man with a history of multiple neoplastic and pre-neoplastic
      gastrointestinal lesions as well as urogenital carcinoma presented for evaluation
      of two asymptomatic skin-colored papules in the head and neck region. Biopsy
      revealed sebaceous neoplasms and immunohistochemical staining was negative for
      the presence of hMSH-2 protein in both specimens. These findings were consistent
      with a diagnosis of Muir-Torre syndrome in the setting of a prior history of
      visceral malignancies. Muir-Torre Syndrome is a rare autosomal dominant
      genodermatosis associated with mutations in mismatch repair proteins, hMSH-2 and
      hMLH-1, which predispose affected patients to visceral malignancies as well as
      sebaceous gland neoplasms.

PMID- 16962020
TI  - Elastosis perforans serpiginosa in a patient with trisomy 21.
AB  - A 12-year-old girl with trisomy 21 (Downs syndrome) presented with an approximate
      2-year history of an asymptomatic eruption on the right upper arm and left
      lateral neck that was clinically and histologically diagnostic of elastosis
      perforans serpiginosa (EPS). EPS is a perforating dermatosis affecting the face,
      ear, neck, extremities, or trunk. It occurs with greater frequency in persons
      with trisomy 21, as well as some other genetic syndromes and after D
      penicillamine therapy. It has also been reported as a sporadic, presumably
      unrelated disorder in several acquired diseases.

PMID- 16962021
TI  - Epidermolytic hyperkeratosis.
AB  - A 13-year-old boy presented to the dermatology clinic for treatment of a
      congenital ichthyosis with a history of generalized erythroderma and trauma
      related blistering at the time of birth. At the time of presentation he was noted
      to have red corrugated hyperkeratotic plaques involving the joint flexures,
      dorsal hands, and neck. Epidermolytic hyperkeratosis is a rare autosomal dominant
      genodermatosis that presents at birth with generalized erythema, blisters and
      erosions. In the subsequent months after birth erythema and blistering improves
      but patients go on to develop hyperkeratotic scaling that is especially prominent
      along the joint flexures, neck, hands and feet. The disease is caused by
      mutations in either keratin 1 or keratin 10. Treatment options include urea or
      alpha-hydroxy acid containing creams as well as topical and systemic retinoids.
      Epidermolytic hyperkeratosis is also known as bullous congenital ichthyosiform
      erythroderma (of Brocq) and disorder of cornification type 3.

PMID- 16962022
TI  - Metastatic basal cell carcinoma: a case report and literature review. How
      accurate is our incidence data?
AB  - A 55-year-old man presented to Skin Cancer Surgery Center of Sacramento in 1995
      for Mohs micrographic surgery of a 1.5-cm nodular basal cell carcinoma located on
      the right superior antihelix and scaphoid fossa. The tumor was excised by Mohs
      micrographic surgery. A recurrent basal cell carcinoma developed at the same site
      5 years later and was treated also by Mohs micrographic surgery. One year later
      (approximately 6 years after the diagnosis of the initial basal cell carcinoma),
      a right parotid mass was noted on routine physical exam. CT scan and fine needle
      aspiration of the mass revealed metastatic basal cell carcinoma. The patient
      underwent excision of the parotid mass followed by radiation therapy. He has done
      well for the past 2 years since the diagnosis of his metastatic lesion. Basal
      cell carcinoma is the most common malignancy in the world. The metastatic
      potential of this tumor has been a cause for concern to many of our patients. We
      report a case of basal cell carcinoma metastatic to the parotid gland and
      critically review the incidence data reported in the literature. We recommended
      the collection of more current and accurate incidence data for basal cell
      carcinoma and metastatic basal cell carcinoma.

PMID- 16962023
TI  - Chondroid syringoma: case report and review of the literature.
AB  - An 84-year-old man presented with an enlarging bluish, painless subcutaneous
      nodule on the glabella. The lesion had been excised 4 years prior and was
      diagnosed as chondroid syringoma, but had gradually regrown. The recurrent lesion
      was treated by surgical re-excision. Histopathological examination was again
      consistent with chondroid syringoma, and showed the following: 1) a chondroid
      matrix, 2) tubuloalveolar structures lined by a double epithelium, 3) ductal
      structures lined by a single epithelium, 4) nests of polygonal cells, and 5) the
      presence of keratinous cysts. Chondroid syringoma is a rare mixed tumor of the
      skin that was first described by Hirsch and Helwig. Characteristically, it is
      composed of a proliferation of epithelial cells set in a myxoid and chondroid
      matrix. Although chondroid syringomas are predominantly benign, malignant forms
      have been reported.

PMID- 16962024
TI  - Eccrine angiomatous hamartoma.
AB  - A 7-year-old girl presented with asymptomatic bruise-like hairy nodules on her
      right lower leg since 8 months of age. Histopathology demonstrated an increased
      number of blood vessels and eccrine glands, thicker collagen bundles, and a
      terminal hair follicle in catagen phase. The patient was diagnosed with multiple
      eccrine pilar angiomatous nevi, an unusual variant of eccrine angiomatous
      hamartomas. The natural course of eccrine angiomatous hamartomas is typically
      slow growth and benign behavior. Simple excision is usually curative and is
      reserved for painful or cosmetically disfiguring lesions. Our patient's nevus is
      large and multifocal, making excision more challenging.

PMID- 16962025
TI  - Acute hemorrhagic edema of infancy.
AB  - An 11-month-old boy initially presented to an outside hospital with fever,
      rhinorrhea, swelling, and papular lesions involving the left foot. He was
      diagnosed with necrotizing fasciitis and he subsequently underwent debridement of
      the lower left leg. Tissue cultures were submitted and were negative.
      Histopathological examination revealed a subcutaneous leukocytoclastic
      vasculitis. The patient was then transferred to the University of California
      Davis Medical Center at which time he was noted to have erythematous nontender
      annular and targetoid patches and plaques with purpuric centers; the lesions were
      scattered over the legs, right foot, flanks, and pinnae. The clinical and
      histopathological findings supported a diagnosis of acute hemorrhagic edema of
      infancy. Supportive care was maintained and the lesions and associated edema
      resolved. Acute hemorrhagic edema of infancy is a form of leukocytoclastic
      vasculitis that, despite a rapid and dramatic onset, has a benign prognosis.

PMID- 16962026
TI  - Necrobiotic xanthogranuloma treated with chlorambucil.
AB  - We report a case of necrobiotic xanthogranuloma that responded to treatment with
      chlorambucil. A 56-year-old man presented with a 5-year history of multiple,
      mildly pruritic, brown-to-violaceous plaques with central ulceration and atrophy
      involving the periorbital area, extremities, and trunk. Laboratory studies showed
      mild leukopenia and a monoclonal gammopathy of the IgG lambda type on serum
      protein immunoelectrophoresis. Histopathological evaluation revealed a dense
      histiocytic infiltrate with hyaline necrobiosis involving the dermis with
      extension to the subcutis. Multiple large multinucleated giant cells and
      scattered lymphocytes were seen. A diagnosis of necrobiotic xanthogranuloma was
      established. The patient was started on chlorambucil initially at 2 mg per day.
      The dose was later increased to 4 mg per day, which resulted in flattening and
      complete resolution of his skin lesions.

PMID- 16962027
TI  - Drug-induced linear IgA bullous dermatosis.
AB  - A 73-year-old man was admitted to the University of California Davis Medical
      Center for treatment of a pleural effusion and congestive heart failure. His
      hospital course was complicated by asymptomatic sustained ventricular tachycardia
      requiring placement of an implantable cardiac defibrillator. The patient was
      treated with vancomycin and cefazolin during the procedure. After 3 days he
      developed tense vesicles over the dorsal aspect of the hands. Perilesional skin
      biopsy showed subepidermal cleavage with a neutrophilic infiltrate. Direct
      immunofluorescence revealed granular IgA and C3 deposition along the dermal
      epidermal junction. A diagnosis of drug-induced linear IgA bullous dermatosis
      secondary to vancomycin was established. Linear IgA bullous dermatosis is a rare
      autoimmune blistering disorder with clinical features that can overlap with
      bullous pemphigoid and dermatitis herpetiformis. Drug-induced linear IgA bullous
      dermatosis is a less common variant that is correspondingly less well
      characterized. Although a variety of medications have been implicated, vancomycin
      is the most common associated drug.

PMID- 16962028
TI  - Melanocortin-1 receptor: loss of function mutations and skin cancer.
AB  - We present a red-haired patient who came to our clinic seeking information
      regarding his predisposition to skin cancer. We discuss the receptor involved in
      hair color and the allelic variants that lead to red hair. These variants are
      often characterized by loss of function mutations, which lead to a predisposition
      to non-melanoma skin cancers, with relative risks reaching as high as a 6.7 in
      one study. Most concerning, however, is that some of these loss of function
      mutations may act synergistically with genetic mutations that cause familial
      melanomas. Thus, red haired patients with familial melanoma syndromes have a
      greater risk of melanoma than those patients with familial melanoma syndromes
      alone.

PMID- 16962029
TI  - [Specificities of immunology...].

PMID- 16962030
TI  - [Autophagy and CD4 T lymphocyte destruction by HIV-1].

PMID- 16962031
TI  - [The rat Toxo1 locus controls the outcome of the toxoplasmic infection according
      to a mendelian mode].

PMID- 16962032
TI  - [Importance of the monitoring of the ARN in the mitochondria of Arabidopsis
      thaliana].

PMID- 16962033
TI  - [CB1 cannabinoid receptor antagonists: a novel approach for the treatment of
      liver fibrosis].

PMID- 16962034
TI  - [Endocytosis and Notch signalling].

PMID- 16962035
TI  - [Vertebrate origins: does the tunic make the man?].

PMID- 16962036
TI  - [KIR3DL2: a new step for the management of patients with Sezary syndrome].

PMID- 16962037
TI  - [Wnt and gastrointestinal stem cells: dangerous connections].

PMID- 16962038
TI  - [To prevent and cure the iron overloads, the hopes of hepcidin].

PMID- 16962039
TI  - [Tiktaalik: a breakthrough towards firm land].

PMID- 16962040
TI  - [Role of chromatin alterations in neurodegeneration induced by polyglutamine
      expanded ataxin-7].

PMID- 16962041
TI  - [Behavioural evidence of nonconscious semantic processing for emotional words].

PMID- 16962042
TI  - [Human embryonic stem cell and haematopoiesis: comparison with the mouse].

PMID- 16962043
TI  - [Notch activation during T-cell leukemogenesis in Ikaros-deficient mice].

PMID- 16962044
TI  - [Epithelial stem cells in the skin].

PMID- 16962046
TI  - [The immunological synapse: models facing facts].
AB  - The notion of immunological synapse is generally associated to a concentric
      structure (a core of T cell receptors surrounded by a ring of adhesion molecules)
      often called "mature synapse". This schematic view has been built on observations
      corresponding to peculiar experimental conditions: very high antigen
      concentration presented by surrogate APCs such as lipid bilayers or B lymphoma.
      These observations have been hastily constituted in a dogma that a "normal"
      synapse should look like this, should form only in the presence of antigen, and
      should trigger a "stop" signal that completely immobilizes the T cell. However,
      when analyzing the interaction between naive T cells and dendritic cells (DC),
      that are the only antigen-presenting cells able to activate naive T cells, a very
      different picture emerges. Firstly, T-DC synapses can form in the absence of
      antigen; therefore antigen recognition is not a prerequisite for synapse
      formation. Secondly, these antigen-independent synapses are likely to play
      several roles, including sensitization of T cells for later antigen detection,
      and delivery of survival signals. Thirdly, in vivo, naive T cells interacting
      with antigen-laden DC do not fully stop, but start to make transient contacts
      with DCs for a few minutes, before continuing their exploration. It is only after
      several hours of this process that T cells eventually immobilize. Fourthly, the
      structure of the T-DC synapse is clearly multifocal, the two cells interacting
      through several tens of tight appositions of a few tens of nm in diameter. These
      numerous tight appositions are reminiscent of the microclusters that have been
      recently described at the T-bilayer interface. Finally, synaptic signaling is not
      a transient initial event, but is sustained for hours. In particular, sustained
      activation of phosphatidylinositol 3-kinase allows the exclusion out of the
      nucleus of FoxO transcription factors, normally maintaining T cells in a
      quiescent state.

PMID- 16962047
TI  - [Processing of MHC class I presented antigens].
AB  - The immune defences of our organism against pathogens and malignant
      transformation rely to a large extent on surveillance by cytotoxic T lymphocytes.
      This surveillance in turn depends on the antigen processing system, which
      provides peptide samples of the cellular protein composition to MHC (major
      histocompatibility complex) class I molecules displayed on the cell surface. To
      continuously and almost in real time provide a representative sample of the array
      of proteins synthesized by the cell, this system exploits some fundamental
      pathways of the cellular metabolism, with the help of several dedicated players
      acting exclusively in antigen processing. Thus, a key element in the turnover of
      cellular proteins, protein degradation by cytosolic proteasome complexes, is
      exploited as source of peptides, by recruiting a minor fraction of the produced
      peptides as ligands for MHC class I molecules. These peptides can be further
      processed and adapted to the precise binding requirements of allelic MHC class I
      molecules by enzymes in the cytosol and endoplasmic reticulum. The latter
      compartment is equipped with several dedicated players helping peptide assembly
      with class I molecules. These include the TAP (transporter associated with
      antigen processing) membrane transporter pumping peptides into the ER, and
      tapasin, a chaperone with a structure similar to MHC molecules that tethers class
      I molecules awaiting peptide loading to the TAP transporter, and mediates
      optimization of MHC class I ligand by a still somewhat mysterious mechanism.
      Additional "house-keeping" chaperones that are known to act in concert in ER
      quality control, assist and control correct folding, oxidation and assembly of
      MHC class I molecules. While this processing system handles exclusively
      endogenous cellular proteins in most cells, dendritic cells employ one or several
      special pathways to shuttle exogenous, internalized proteins into the system, in
      a process referred to as cross-presentation. Deciphering the cell biological
      mechanism creating the link between the endosomal and secretory pathways that
      enables cross-presentation is one of the challenges faced by contemporary
      research in the field of MHC class I antigen processing.

PMID- 16962048
TI  - [Defect in lytic granule exocytosis: several causes, a same effect].
AB  - An in vivo disturbance of lymphocyte homeostasis occurs during the course of the
      hemophagocytic syndrome (HS). HS is a severe and often fatal syndrome resulting
      from potent and uncontrolled activation and proliferation of T-lymphocytes,
      mainly polyclonal CD8 lymphocytes, leading to excessive macrophage activation,
      high level of proinflammatory cytokine production and multiple deleterious
      effects. The onset of HS characterizes several inherited disorders in humans. In
      most of these conditions, the molecular defect impairs the granule-dependent
      cytotoxic activity of lymphocytes, thus highlighting the determinant role of this
      function in driving back the immune system to a state of equilibrium following
      infection. Several lines of evidence suggest that an increase in the expansion
      phase rather than a decrease in the contraction phase of the CD8+ T cells
      population characterizes the HS. Failure to kill antigen presenting cells through
      a transaction mechanism of cytotoxic cells should favor a sustained response,
      although the mechanism may be more complex than simple decrease of antigen load.
      Defect in the granule dependent cytotoxic function of lymphocytes result from
      perforin mutation in familial hemophagocytic lymphohistiocytosis type 2, from
      Munc13-4 (UNC13D) mutation in familial hemophagocytic lymphohistiocytosis type 3,
      from Rab27a mutation in Griscelli syndrome type 2, and from CHS/LYST mutation in
      Chediak-Higashi syndrome. The characterization of the molecular causes leading to
      these conditions identified Rab27a and Munc13-4 as two critical effectors of the
      exocytic machinery, required for the terminal transport/docking or priming of the
      cytotoxic granules, respectively. Different members of the Rab and Munc13 family
      of proteins are also used in neurotransmitter release at the neurological
      synapse, highlighting the similarity of the mechanisms regulating both secretory
      pathways. Future investigations regarding HS will continue to elucidate this
      exocytic pathway machinery and improve our understanding of how it finely
      regulates the immune response, an area that is likely to be useful for
      therapeutic intervention.

PMID- 16962049
TI  - [NK cells and innate immunity to malaria].
AB  - Innate immune response against Plasmodium falciparum (Pf), a causative agent of
      human malaria, is the result of several thousand years of co-evolution between
      the parasite and his host. An early IFN-gamma production during infection is
      associated with a better evolution of the disease. Natural killer (NK) cells are
      among the first cells in peripheral blood to produce IFN-gamma in response to Pf
      infected erythrocytes (Pf-E). NK cells are found in blood, in secondary lymphoid
      organs as well as in peripheral non-lymphoid tissues. They participate in host
      innate responses that occur upon viral and intracytoplasmic bacterial infections,
      but also during the course of tumor development and allogeneic transplantation.
      These lymphocytes are not only important players of innate effector responses,
      but also participate in the initiation and development of adaptive immune
      responses. In addition, direct sensing of Pf infection by NK cells induces their
      production of the proinflammatory chemokine IL-8, suggesting a role for NK cells
      in the recruitment and the activation of other cells during malaria infection.
      Several other cell subsets are involved in the innate immune response to Pf.
      Dendritic cells, macrophages, gamma delta T cells, NKT cells are able to sense
      the presence of the parasite. Along this line, the presence of IL-12 is necessary
      to NK cell IFN-gamma production and a functional cooperation takes place between
      macrophages and NK cells in the context of this parasitic infection. In
      particular, IL-18 produced by macrophages is a key factor for this NK response.
      However, the molecular basis of Pf-E recognition by NK cells as well as the
      functional role of NK cell responses during the course of the disease remain to
      be adressed.

PMID- 16962050
TI  - [Immunology of pregnancy: renewed interest].
AB  - The long-standing question of pregnancy immunological paradox has been generating
      renewed interest. Recent insights have emerged from studies in pregnant mice and
      humans demonstrating a number of mechanisms that prevent potentially harmful
      effects of maternal anti-paternal allo-antibodies (complement inhibition, partial
      deletion of maternal B cells specific of paternal antigens), cytotoxic CD8+ T
      cells (lack of HLA-A and HLA-B expression on trophoblast, local immunosuppressive
      molecules, transient tolerance of paternal allo-antigens specific T cells) and
      uterine NK cells directed against fetal-derived trophoblast cells (limited NK
      cytotoxic potential, trophoblast resistance to NK killing). Interestingly, it
      appears that not only decidual NK cell/trophoblast interactions are not harmful
      for the fetus but are beneficial for the placental vascularization and its
      subsequent development. A recent report has indeed demonstrated that during
      pregnancy most of the combinations of uterine KIR (killer cell immunoglobulin
      like receptor) NK cell receptors and fetal HLA-C molecules expressed by
      trophoblast led to normal pregnancies, whereas mothers lacking activating KIR of
      the AA genotype when the fetus possessed HLA-C of the C2 group were at a greatly
      increased risk of severe preeclampsia pathology.

PMID- 16962051
TI  - [Cytokine therapies in HIV infection].
AB  - The theoretical objectives of cytokine therapies in HIV infection are to impact T
      cell homeostasis and/or to improve immune functions or the mobilization of the
      HIV reservoir. Among cytokines, IL-2 and IL-7 are promising agents under clinical
      evaluation. Intermittent administration of IL-2 is by far the furthest studied
      strategy in HIV infection. This cytokine increases CD4 T lymphocytes in HIV
      infected individuals. Recent clinical data showed that this effect is sustained
      over years. IL-2 therapy induces a peripheral expansion of T cells as a
      consequence of prolonged survival of T cells and decreased immune activation.
      These effects suggest that a cytokine therapy may interfere with critical factors
      of HIV disease. Recent data provide arguments that IL-2 therapy improves immune
      functions in HIV-infected patients. Whether these effects may be translated into
      clinical benefits is under evaluation in ongoing phase III studies. The potential
      interest of IL-7 in the treatment of HIV-infection is based on its crucial role
      on T cell homeostasis both in thymic output and peripheral T proliferation and
      survival. Although no data in human are still available, recent studies provide
      arguments to assess this cytokine in HIV infection. Phase I studies are ongoing
      or planned.

PMID- 16962052
TI  - [Immunotherapy of cancer: promise and reality].
AB  - The notion that the immune system regulates cancer development is now well
      established. An overwhelming amount of data from animal models, together with
      compelling data from human patients, indicate that the immune system is
      instrumental in scanning and irradicating tumors. Analysis of individuals with
      congenital or acquired immunodeficiencies or patients undergoing
      immunosuppressive therapy has documented a highly elevated incidence of virally
      induced malignancies and cancers compared with immunocompetent individuals [1-3].
      During the last decade, thanks to the breakthoughts in understanding the
      molecular mechanisms responsible for immune activation, the tumor antigen
      identification, the dendritic cell biology, the immunogenecity of tumors, the
      immune escape mechanisms, the host-tumor relationship, we are facing a new area
      of tumor immunotherapy. The basic advances were translated in therapeutical
      applications and have changed the view of immunotherapy from "a dream scenario"
      to a clinical fourth modality to cancer treatments. Multiple cancer trials using
      active immunization with vaccines or adoptive immunotherapy have been conducted
      with only very limited success. There are still a number of issues that still
      need to be resolved including a better understanding of immune escape mechanisms.
      Cancer vaccines continue to be evaluated and may lead to the emergence of
      clinically useful new treatments. A comprehensive approach to define the
      intricate molecular program initiated by tumor cells to resist to escape and the
      immune system of the host may help in breaking down the barriers to a more
      adapted cancer immunotherapy.

PMID- 16962053
TI  - [Children'rights: how they are respected?].

PMID- 16962054
TI  - [1918 lurks in everybody's mind. The "Spanish" flu and us].
AB  - The 1918 pandemic is still unique in the history of flu pandemics. The
      pathogenicity of the virus was extreme, and young adults more than infants and
      old people were its main victims. Many a death was caused by complications. The
      response of the French authorities didn't live up to the emergency requirements.
      Hospitals being requisitioned by the military, the civilian population lacked
      everything: beds, doctors, nurses, ambulances, drugs. For want of preventive or
      curative medicine, authorities could have done very little at any rate: public
      health measures (quarantine and isolation of the sicks) were unable to stop
      contagion. More than the war itself, present day historians indict the war
      boosted increase in railways and sea communications between the continents and
      between the rear and the front. This momentous growth in transportation
      activities brought about a "bacterial equalization" throughout social categories
      and regions of the world. A most singular episode, whose historical chances to
      replicate within the next ten years are rather slim.

PMID- 16962055
TI  - [The Baron Guillaume Dupuytren].

PMID- 16962056
TI  - [The fragility of the US Supreme Court decision Roe v. Wade].

PMID- 16962059
TI  - Car following decisions under three visibility conditions and two speeds tested
      with a driving simulator.
AB  - The National Highway Traffic Safety Administration web site reports that rear-end
      collisions in the United States exceed 1.5 million per year, or approximately 23%
      of all vehicle crashes. Car following behavior and the decision-making habits of
      drivers seem fundamental to understanding how to avoid these rear-end crashes.
      The present research aimed to reveal factors that govern car following under
      conditions of reduced visibility. It employed a KQ-Vection high-fidelity driving
      simulator to measure the behavior of automobile drivers following a lead vehicle
      at 13.4 m/s (30 MPH) or 22.4 m/s (50 MPH) under three visibility conditions-
      clear or one of two densities of simulated fog. At the higher speed, fog
      conditions separated participants into a group that stayed within visible range
      of the lead car, even though the headway time violated the NHTSA recommendations
      for the speed involved, and another group that lagged beyond the visible range.
      Data were compared to the model of Van Winsum for car following (The human
      element in car following models. Transportation Research Part F 2, 1999).
      Contrast and image size measurements allowed comparison to a standard contrast
      sensitivity function and allowed estimation of the JND term in the Van Winsum
      model.

PMID- 16962060
TI  - Occupational injury in the French sea fishing industry: a comparative study
      between the 1980s and today.
AB  - This study aims at comparing two data bases related to occupational injuries in
      the French sea fishing industry: a data base created between 1977 and 1980, a
      data base created between 1996 and 2001. These bases were made from report forms
      filled out by fishermen after an accident. The study focuses on the accidents
      occurring when the vessel is in the process of fishing. In the 1980s, as well as
      today, the processing of fishing gear seems to be a very dangerous task,
      correlated with the risk of being "struck by, swept along, pinned" by the
      elements of the rigging and the risk of serious injuries. The processing and
      handling of the catch also cause a large amount of accidents; during these tasks,
      fishermen have to cope with two main risks: being "cut or pricked" and making an
      "excessive effort, awkward movement". Rate and features of occupational accidents
      do not show notable evolution. These findings lead us to question the different
      prevention measures implemented in France during the last few decades and to
      propose new prevention direction.

PMID- 16962061
TI  - Aligning confidence with accuracy: revisiting the role of feedback.
AB  - Evaluation point feedback was used to align confidence judgments with
      accurate/inaccurate responding to general knowledge questions. Rehearsal of item
      answer pairs and three evaluation systems based on a scoring rule had different
      effects on confidence, accuracy and their relationship. Using standard
      calibration measures (Yates, J.F., (1990). Judgment and Decision Making.
      Englewood Cliffs, NJ: Prentice Hall) we found that a point system comprising of
      both rewarding (positive) and punishing (negative) consequences produced the best
      performance across levels of knowledge in comparison to all-rewarding and all
      penalty rules.

PMID- 16962062
TI  - Identification, sequencing and expression of peroxidoxin genes from Leishmania
      aethiopica.
AB  - Cutaneous leishmaniasis (CL) is a painful, disfiguring and debilitating disease
      prevalent in Ethiopia and other countries around the world. In Ethiopia, CL is
      primarily caused by Leishmania aethiopica and less often by L. tropica and L.
      major. The intracellular survival mechanisms of Leishmania parasites are still
      not well understood. Recently a new family of antioxidant enzymes called
      peroxidoxins have been identified that play an important role in parasite
      survival. In this study, we have identified two distinct peroxidoxin genes (Pxn1
      and Pxn2) that are part of a multi-gene family in L. aethiopica. Protein sequence
      analysis showed that Pxn1 and Pxn2 are highly homologous to peroxidoxins from
      other Leishmania species. We have found that L. aethiopica Pxn1 is predominantly
      expressed in amastigotes and stationary phase promastigotes, whereas Pxn2 is
      constitutively expressed in the different stages of the parasite. This pattern of
      RNA expression is consistent with patterns seen in some Leishmania species, but
      not all. Data from this study will be helpful in enhancing vaccine strategies and
      drug studies targeted towards peroxidoxins.

PMID- 16962063
TI  - Real-time quantitative allele discrimination assay using 3' locked nucleic acid
      primers for detection of low-percentage mosaic mutations.

PMID- 16962064
TI  - Ysp2 mediates death of yeast induced by amiodarone or intracellular
      acidification.
AB  - Recently we have found that the drug amiodarone induces apoptosis in yeast, which
      is mediated by reactive oxygen species (ROS). Here we have used this finding as a
      tool to screen for genes involved in the death program. We have described a novel
      mitochondrial protein, Ysp2, acting in the amiodarone-induced death cascade.
      After amiodarone addition both the control and amiodarone-resistant ysp2-deleted
      cells formed ROS, but the mutant (unlike the control) did not undergo the
      mitochondrial thread-to-grain transition. To test whether the action of Ysp2 is
      amiodarone-specific we tried to induce PCD by other agents. We have found that
      acetic acid-induced PCD also depends on Ysp2. We also demonstrate that, like
      acetic acid, propionic acid or nigericin triggered intracellular acidification
      causing ROS-dependent death. We suggest that intracellular acidification results
      in the protonation of superoxide anion (O2-*) to form HO2, one of the most
      aggressive ROS, which in turn induces Ysp2-mediated PCD.

PMID- 16962065
TI  - Intimate partner violence and depressive symptoms in women: cognitive schemas as
      moderators and mediators.
AB  - In this study the role of cognitive schemas as moderators and mediators between
      intimate partner violence and depressive symptoms was examined. The sample
      consisted of 312 women who had suffered an abusive relationship. Participants
      completed measures of physical, psychological and sexual abuse, maladaptive
      cognitive schemas (disconnection and rejection, autonomy, and other
      directedness), and depression. The evidence for a moderation effect was low and
      mainly restricted to schemas of the impaired autonomy domain. In contrast, the
      results supported mediational models in which violence was associated to the
      cognitive schemas, and these in turn were associated to depressive symptoms.
      Mediation was partial, with the schemas of the disconnection and rejection domain
      explaining most of the association between violence and depression. Finally,
      several explanations for these findings are examined, and their implications for
      the concept and measure of the cognitive schemas are discussed.

PMID- 16962066
TI  - A randomized controlled trial of the effect of D-cycloserine on extinction and
      fear conditioning in humans.
AB  - Previous research has shown that D-cycloserine (DCS) facilitates extinction of
      Pavlovian fear conditioning in rats and enhances exposure therapy in humans. The
      aim of this study was to test the effect of DCS on extinction of fear
      conditioning in humans. In three experiments, 238 participants were given either
      DCS (50 or 500 mg) or placebo 2-3 h before extinction training following a
      differential shock conditioning paradigm. Clear extinction and recovery (return
      of fear) effects were observed on both skin conductance and self-reported shock
      expectancy measures in three studies. DCS had no influence on these effects. The
      same pattern was observed when the analysis was restricted to aware participants
      or to good conditioners, when fear-relevant cues (pictures of snakes) were used
      as the conditioned stimuli, or when analysis was restricted to heightened snake
      fearful participants. These results suggest that DCS may not enhance the
      extinction, or prevent the recovery, of learned fear in a differential Pavlovian
      conditioning paradigm in humans. Further experimental research is needed to
      better understand the mechanisms underlying the therapeutic effects of DCS.

PMID- 16962067
TI  - Critical role of the FERM domain in Pyk2 stimulated glioma cell migration.
AB  - The strong tendency of malignant glioma cells to invade locally into surrounding
      normal brain precludes effective surgical resection, reduces the efficacy of
      radiotherapy, and is associated with increased resistance to chemotherapy
      regimens. We report that the N-terminal FERM domain of Pyk2 regulates its
      promigratory function. A 3-dimensional model of the Pyk2 FERM domain was
      generated and mutagenesis studies identified residues essential for Pyk2
      promigratory function. Model-based targeted mutations within the FERM domain
      decreased Pyk2 phosphorylation and reduced the capacity of Pyk2 to stimulate
      glioma cell migration but did not significantly alter the intracellular
      distribution of Pyk2. Expression of autonomous Pyk2 FERM domain fragments
      containing analogous mutations exhibited reduced capacity to inhibit glioma cell
      migration and Pyk2 phosphorylation relative to expression of an autonomous wild
      type FERM domain fragment. These results indicate that the FERM domain plays an
      important role in regulating the functional competency of Pyk2 as a promigratory
      factor in glioma.

PMID- 16962068
TI  - Role of integrin-linked kinase in vascular smooth muscle cells: regulation by
      statins and angiotensin II.
AB  - Our goal was to characterize the role of integrin-linked kinase (ILK) in vascular
      smooth muscle cells (VSMC), which play a crucial role in atherogenesis.
      Transfection of VSMC with wild-type and dominant-negative ILK cDNA constructs
      revealed that ILK mediates migration and proliferation of VSMC but has no effect
      on VSMC survival. The pro-atherogenic mediator angiotensin II increases ILK
      protein expression and kinase activity while statin treatment down-regulates ILK
      in VSMC. Functionally, ILK is necessary for angiotensin II-mediated VSMC
      migration and proliferation. In VSMC transduced with dominant-negative ILK,
      statins mediate an additive inhibition of VSMC migration and proliferation, while
      transfection with wild-type ILK is sufficient to overcome the inhibitory effects
      of statin treatment on VSMC migration and proliferation. In vivo, ILK is
      expressed in VSMC of aortic sections from wild-type mice where it is down
      regulated following statin treatment and up-regulated following induction of
      atherosclerosis in apoE-/- mice. These data identify ILK as a novel target in
      VSMC for anti-atherosclerotic therapy.

PMID- 16962069
TI  - Angiogenic potential of CD44+ CD90+ multipotent CNS stem cells in vitro.
AB  - Although it is now clear that several subpopulations of neural stem cells (NSCs)
      exist during early development and adulthood, the angiogenic potential of NSCs
      remains a subject of debate. Here, we report that CD44(+) CD90(+) cells isolated
      from primary neurospheres can form vascular-tube structures in vitro. NSCs
      isolated from the mouse embryonic cortex formed neurospheres when cultured in
      serum-free medium containing 20ng/ml basic fibroblast growth factor (bFGF).
      CD44(+) CD90(+) cells were enriched from the neurospheres using an EPICS ALTRA
      flow cytometer, and antibodies against CD44 and CD90. The purified CD44(+)
      CD90(+) cells generated neurospheres, and differentiated into neurons and
      astrocytes. When the cells were inoculated into collagen gels and cultured with
      20% fetal bovine serum plus bFGF for 7 days, vascular tube-like structures were
      formed. These results indicate that CD44(+) CD90(+) cells have the ability to
      generate neurospheres and to form vascular tubes.

PMID- 16962070
TI  - 20(S)-Ginsenoside Rg3 prevents endothelial cell apoptosis via inhibition of a
      mitochondrial caspase pathway.
AB  - Ginseng, refering to the roots of the species of the genus Panax ginseng, has
      been widely used in traditional oriental medicine for its wide spectrum of
      medicinal effects, such as anti-inflammatory, anti-tumorigenic, adaptogenic, and
      anti-aging activities. Many of its medicinal effects are attributed to the
      triterpene glycosides known as ginsenosides. In this study, we report a novel
      anti-apoptotic activity of 20(S)-ginsenoside Rg3 ((20S)Rg3) and its underlying
      molecular mechanism in human endothelial cells (ECs). ECs undergo apoptosis
      associated with increased LEHDase (caspase-9) and DEVDase (caspase-3) activity
      and DNA fragmentation after 24h of serum deprivation. These apoptotic markers
      were suppressed by the addition of (20S)Rg3. (20S)Rg3 increased the expression of
      Bax and conversely decreased Bcl-2. (20S)Rg3 potently induced a rapid and
      sustained Akt activation and Bad phosphorylation, resulting in the inhibition of
      mitochondrial cytochrome c release. These anti-apoptotic activities of (20S)Rg3
      were significantly abrogated in cells expressing dominant negative Akt. Taken
      together, our results suggest that (20S)Rg3 prevents EC apoptosis via Akt
      dependent inhibition of the mitochondrial apoptotic signaling pathway. The novel
      property of (20S)Rg3 may be valuable for developing new pharmaceutical means that
      will control unwanted endothelial cell death at the site of vascular injury.

PMID- 16962071
TI  - Inhibition of inflammatory response in transgenic fat-1 mice on a calorie
      restricted diet.
AB  - Both n-3 fatty acids (n-3 FA) and calorie-restriction (CR) exert anti
      inflammatory effects in animal models of autoimmunity and inflammation. In the
      present study we investigated the synergistic anti-inflammatory effects of n-3 FA
      and CR on LPS-mediated inflammatory responses using fat-1 transgenic mice that
      generate n-3 FA endogenously. Wild-type (WT) and fat-1 mice were maintained on ad
      libitum (AL) or CR (40% less than AL) diet for 5 mo; splenocytes were cultured in
      vitro with/without LPS. Our results show: (i) no difference in body weights
      between WT and fat-1 mice on AL or CR diets, (ii) lower n-6/n-3 FA ratio in
      splenocytes from fat-1 mice on both AL and CR diets, (iii) significant reduction
      in NF-kappaB (p65/p50) and AP-1 (c-Fos/c-Jun) DNA-binding activities in
      splenocytes from fat-1/CR mice following LPS treatment, and (iv) significant
      reduction in kappaB- and AP-1-responsive IL-6 and TNF-alpha secretion following
      LPS treatment in splenocytes from fat-1/CR mice. The inhibition of LPS-mediated
      effects was more pronounced in fat-1/CR mice when compared to fat-1/AL or WT/CR
      mice. These data show that transgenic expression of fat-1 results in decreased
      pro-inflammatory n-6 FA, and demonstrate for the first time that splenocytes from
      fat-1 mice on CR diet exhibit reduced pro-inflammatory response when challenged
      with LPS. These results suggest that n-3 lipids with moderate CR may confer
      protection in autoimmune and inflammatory diseases.

PMID- 16962072
TI  - Substrate characterisation of a recombinant sulfotransferase SULT1 and mRNA
      expression in chub (Leuciscus cephalus) tissues.
AB  - We have studied the role and regulation of sulfonation of xenobiotics and
      endogenous substrates in Leuciscus cephalus, an abundant and environmentally
      relevant freshwater fish. A sulfotransferase 1 (SULT1) cDNA and promoter region
      was cloned from chub liver and the cDNA expressed in Escherichia coli. The
      translated protein displayed 51% and 50% amino acid identity to mSULT1D1,
      hSULT1A1, respectively. We identified two conserved co-substrate binding motifs
      for 3'-phosphoadenosine 5'-phosphosulfate: RKGxxGDWKxxFT and YPKSGTxW. The
      recombinant SULT displayed a strong preference towards the isoflavones genistein
      (K(m)=1.7 microM) and daidzein (K(m)=4.4 microM) and lesser activity towards the
      endogenous substrate dopamine. Based on sequence identity and substrate
      preferences, the SULT was classified as SULT1,3. SULT1,3 mRNA expression was
      highest in the liver and kidney with low levels expressed in brain, gonad, and
      gill. Mature males displayed higher hepatic SULT1,3 mRNA expression compared to
      females. Analysis of the promoter region revealed several putative half
      palindromic estrogen response elements (ERE).

PMID- 16962073
TI  - Protective effect of monosialoganglioside GM1 against chemically induced
      apoptosis through targeting of mitochondrial function and iron transport.
AB  - Exogenous treatment with monosialoganglioside GM1 has been described to afford
      protection against different apoptotic insults. However, the underlying
      mechanisms remain to be determined. In this study, we focused on the effect of
      GM1 on the apoptotic cascade induced by benzo[a]pyrene (B[a]P) in rat hepatic
      F258 epithelial cells. We first demonstrated that a co-treatment with GM1 (80
      microM) reduced B[a]P (50 nM)-induced apoptosis as evidenced by a decrease of
      both cell population exhibiting nuclear fragmentation and caspase 3 cleavage and
      activity. We next showed that the p53 phosphorylation and nuclear translocation
      as well as the intracellular alkalinization related to Na+/H+ exchanger 1 (NHE1)
      activation, two early events of the apoptosis induced by B[a]P, were not
      inhibited by GM1. In contrast, the late mitochondria-dependent acidification
      elicited by B[a]P was inhibited by GM1 co-treatment, and an inhibition of the
      oxidative stress was also observed. Because GM1 has been shown to reduce the low
      molecular weight iron content related to ethanol-induced oxidative stress, we
      finally investigated the involvement of iron under our conditions. Using the two
      iron chelators deferiprone and desferrioxamine, we clearly showed that iron
      played an important role in B[a]P-induced apoptosis in F258 cells, and that B[a]P
      treatment resulted in a significant GM1-sensitive increase in (55)Fe uptake. In
      conclusion, our results indicate that exogenous GM1 partly prevents B[a]P-induced
      apoptosis by interfering with mitochondria-related intracellular acidification
      and iron transport.

PMID- 16962074
TI  - A twin study of attention-deficit/hyperactivity disorder dimensions rated by the
      strengths and weaknesses of ADHD-symptoms and normal-behavior (SWAN) scale.
AB  - BACKGROUND: When symptom rating scales are used in the general population, there
      is severe skewness, with many individuals having no symptoms. While this has
      major implications for genetic designs that require extremely discordant and
      concordant (EDAC) siblings, little is known of the genetics of scales which seek
      to differentiate within the "no ADHD symptom" group. METHODS: Parents of
      Australian twins completed two attention-deficit/hyperactivity disorder (ADHD)
      questionnaires, the Australian Twin Behaviour Rating Scale (ATBRS), based on
      conventional DSM-IV symptom scores, and the Strengths and Weaknesses of ADHD
      Symptoms and Normal-Behavior (SWAN) scale, which includes above-average
      performance on attention and activity. The two scales were compared in two age
      groups of same-sex twins, 528 pairs aged 6 to 9 and 488 pairs aged 12 to 20.
      RESULTS: Parents reported higher levels of activity and attention in their twins
      when reporting using the SWAN scale than when using the ATBRS, and while the
      monozygotic (MZ) correlations were similar on both scales, the dizygotic (DZ)
      correlations were consistently higher on the SWAN. On DSM-IV based scales,
      parents exaggerated differences within those sibling pairs in the "with few ADHD
      symptoms" category. CONCLUSIONS: The SWAN may provide a more realistic
      description of the ADHD phenotype for the selection of twin and sibling pairs for
      genetic analysis.

PMID- 16962075
TI  - Neural substrates of knowledge of hand postures for object grasping and
      functional object use: evidence from fMRI.
AB  - A number of lines of evidence suggest that computation of hand posture differs
      for object grasping as compared to functional object use. Hand shaping for
      grasping appears to rely strongly upon calculations of current object location
      and volume, whereas hand shaping for object use additionally requires access to
      stored knowledge about the skilled manipulation specific to a given object. In
      addition, the particular hand postures employed for functional object use may be
      either prehensile (clenching, pinching) or non-prehensile (e.g., palming,
      poking), in contrast to the prehensile postures that are obligatory for grasping.
      In this fMRI study, we assessed the hypothesis that a left-hemisphere-lateralized
      system including the inferior parietal lobe is specifically recruited for the
      computation and recognition of hand postures for functional object use. Fifteen
      subjects viewed pictures of manipulable objects and determined whether they would
      be grasped with a pinch or clench (Grasp condition), functionally used with a
      pinch or clench (Prehensile Use condition), or functionally used with a palm or
      poke hand posture (Non-prehensile Use condition). Despite the fact that the
      conditions were equated for behavioral difficulty, significantly greater
      activations were observed in the left inferior frontal gyrus (IFG), posterior
      superior temporal gyrus (STG), and inferior parietal lobule (IPL) in Non
      prehensile Use trials as compared to Grasp trials. Comparison of Non-prehensile
      Use and Prehensile Use activations revealed significant differences only in the
      left IPL. These data confirm the importance of the left IPL in storing knowledge
      of hand postures for functional object use, and have implications for
      understanding the interaction of dorsal and ventral visual processing systems.

PMID- 16962077
TI  - Sex differences in brain expression of X- and Y-linked genes.
AB  - The X chromosome plays an important role in brain development and function, as
      evidenced by its disproportionately high content of genes whose mutations cause
      mental retardation. These X-linked brain genes may play a role in sexual
      differentiation if they are expressed at a higher level in XX females than in XY
      males, due to incomplete X inactivation in females. The expression of several X
      escapee genes is indeed higher in brain tissues from females when compared to
      males. In mouse, some of the sex differences are only found in adult brains but
      not in other tissues. Determining the brain expression pattern of these X escapee
      genes is important for a better understanding of their role in the neurological
      phenotypes of XO Turner syndrome.

PMID- 16962076
TI  - Increased extracellular concentrations of norepinephrine in cortex and
      hippocampus following vagus nerve stimulation in the rat.
AB  - The vagus nerve is an important source of afferent information about visceral
      states and it provides input to the locus coeruleus (LC), the major source of
      norepinephrine (NE) in the brain. It has been suggested that the effects of
      electrical stimulation of the vagus nerve on learning and memory, mood, seizure
      suppression, and recovery of function following brain damage are mediated, in
      part, by the release of brain NE. The hypothesis that left vagus nerve
      stimulation (VNS) at the cervical level results in increased extracellular NE
      concentrations in the cortex and hippocampus was tested at four stimulus
      intensities: 0.0, 0.25, 0.5, and 1.0 mA. Stimulation at 0.0 and 0.25 mA had no
      effect on NE concentrations, while the 0.5 mA stimulation increased NE
      concentrations significantly in the hippocampus (23%), but not the cortex.
      However, 1.0 mA stimulation significantly increased NE concentrations in both the
      cortex (39%) and hippocampus (28%) bilaterally. The increases in NE were
      transient and confined to the stimulation periods. VNS did not alter NE
      concentrations in either structure during the inter-stimulation baseline periods.
      No differences were observed between NE levels in the initial baseline and the
      post-stimulation baselines. These findings support the hypothesis that VNS
      increases extracellular NE concentrations in both the hippocampus and cortex.

PMID- 16962078
TI  - Ultrastructural anatomy of the renal nerves in rats.
AB  - The innervation within mammalian kidneys (intrinsic innervation) has been
      extensively described in the literature, particularly for rats. In contrast,
      there is still a lack of detailed description of the morphology of the extrinsic
      renal nerves leading to the kidney. The aim of the present study was to describe,
      in detail, the morphology of the renal nerves in rats. Left renal nerves were
      evaluated in 6 normal adult Wistar rats. After nerve recordings, in order to
      ascertain that the nerves studied were the extrinsic renal nerves, rats were
      killed and the nerves prepared for transmission electron microscopy. Morphometry
      was carried out with the aid of computer software. The total numbers of
      myelinated and unmyelinated fibers were 22+/-6 and 1246+/-110, respectively, with
      a ratio of unmyelinated/myelinated fiber of 109+/-26. The diameters of myelinated
      fibers showed an unimodal distribution with a peak at 3.0 microm but more than
      17% of the fibers showed diameters larger than 5 microm. Unmyelinated fiber
      distribution was unimodal, with peak between 0.5 and 0.7 microm. The present
      study adds new information on the morphology of renal nerves in rats and provides
      morphological basis for further studies involving the structural basis of altered
      renal responses in conditions such as hypertension, ageing, diabetes and
      peripheral neuropathies.

PMID- 16962079
TI  - Effects of short- and long-term estrogen and progesterone replacement on
      behavioral responses and c-fos mRNA levels in female rats after acute cocaine
      administration.
AB  - It is well established that there are estrous cycle differences in cocaine
      induced behavioral activity, implicating fluctuations in levels of estrogen and
      progesterone throughout the cycle in these alterations in behavior. However, the
      mechanisms by which steroids alter cocaine-induced behavioral responses have yet
      to be determined. The aim of this study was to determine whether short- or long
      term estrogen and progesterone administration differentially alters behavioral
      responses to cocaine. Estrogen (50 microg) was administered 30 min or 48 h before
      cocaine (15 mg/kg, i.p.) administration; progesterone (500 microg) was
      administered 30 min or 24 h before cocaine. Short-term estrogen replacement
      decreased cocaine-induced ambulations. Short-term progesterone decreased rearing,
      whereas long-term progesterone decreased ambulations. Although cocaine increased
      levels of c-fos mRNA, none of the estrogen or progesterone replacement paradigms
      affected this measure. Because long-term estrogen replacement has been shown to
      have no effect on locomotor activity after acute cocaine administration, our
      observations suggest that short-term estrogen may underlie behavioral
      alterations. These findings suggest that after acute cocaine administration,
      while estrogen may activate only membrane receptors to alter behavioral responses
      to cocaine, progesterone activates both nuclear and membrane receptors.

PMID- 16962080
TI  - Divergent projections of catecholaminergic neurons in the nucleus of the solitary
      tract to limbic forebrain and medullary autonomic brain regions.
AB  - The nucleus of the solitary tract (NTS) is a critical structure involved in
      coordinating autonomic and visceral activities. Previous independent studies have
      demonstrated efferent projections from the NTS to the nucleus
      paragigantocellularis (PGi) and the central nucleus of the amygdala (CNA) in rat
      brain. To further characterize the neural circuitry originating from the NTS with
      postsynaptic targets in the amygdala and medullary autonomic targets, distinct
      green or red fluorescent latex microspheres were injected into the PGi and the
      CNA, respectively, of the same rat. Thirty-micron thick tissue sections through
      the lower brainstem and forebrain were collected. Every fourth section through
      the NTS region was processed for immunocytochemical detection of tyrosine
      hydroxylase (TH), a marker of catecholaminergic neurons. Retrogradely labeled
      neurons from the PGi or CNA were distributed throughout the rostro-caudal
      segments of the NTS. However, the majority of neurons containing both retrograde
      tracers were distributed within the caudal third of the NTS. Cell counts revealed
      that approximately 27% of neurons projecting to the CNA in the NTS sent
      collateralized projections to the PGi while approximately 16% of neurons
      projecting to the PGi sent collateralized projections to the CNA. Interestingly,
      more than half of the PGi and CNA-projecting neurons in the NTS expressed TH
      immunoreactivity. These data indicate that catecholaminergic neurons in the NTS
      are poised to simultaneously coordinate activities in limbic and medullary
      autonomic brain regions.

PMID- 16962081
TI  - Hypertension downregulates the expression of brain-derived neurotrophic factor in
      the ischemia-vulnerable hippocampal CA1 and cortical areas after carotid artery
      occlusion.
AB  - We studied the effect of hypertension on brain damage and brain-derived
      neurotrophic factor (BDNF) expression in the hippocampal formation and cerebral
      cortex after permanent occlusion of bilateral common carotid arteries (CCA). Two
      groups of rats were used, including normotensive Wistar-Kyoto (WKY) rat and
      spontaneous hypertensive rat (SHR). Each group contained sham operation, 1 week
      and 4 weeks after bilateral CCA occlusion (n=5-10 in each time point). The blood
      pressure showed a significant elevation in WKY rats from 1 h after operation to 4
      weeks before sacrifice (P<0.05), but was not changed in SHR (P>0.05). However,
      rectal temperature showed no significant change after operation in WKY rat and
      SHR (P>0.05) and showed no significant difference at any time point between WKY
      rat and SHR (P>0.05). Hematoxylin and eosin staining showed SHR had a
      significantly larger necrotic volume than WKY rats (n=10 in each group, 6044+/
      6895 microm(3) vs. 144+/-174 microm(3), P<0.05) at 4 weeks after ischemia. In
      SHR, BDNF immunoreactivity and mRNA decreased significantly from 1 week to 4
      weeks in both the hippocampal CA1 and cortical areas (P<0.01) but decreased
      transiently in dentate gyrus. However, in WKY rats, BDNF immunoreactivity and
      mRNA decreased transiently at 1 week (P<0.05) and recovered at 4 weeks after
      cerebral ischemia. Our study demonstrates that after bilateral CCA occlusion,
      preexisting hypertension may aggravate the brain injury and downregulate the
      expression of BDNF immunoreactivity and mRNA in the ischemia-vulnerable
      hippocampal CA1 and cortical areas but not in ischemia-resistant dentate gyrus.

PMID- 16962082
TI  - Memory functions of children born with asymmetric intrauterine growth
      restriction.
AB  - OBJECTIVE: Learning difficulties are frequently diagnosed in children born with
      intrauterine growth restriction (IUGR). Models of various animal species with
      IUGR were studied and demonstrated specific susceptibility and alterations of the
      hippocampal formation and its related neural structures. The main purpose was to
      study memory functions of children born with asymmetric IUGR in a large-scale
      cohort using a long-term prospective paradigm. METHODS: One hundred and ten
      infants diagnosed with IUGR were followed-up from birth to 9 years of age. Their
      performance was compared with a group of 63 children with comparable gestational
      age and multiple socioeconomic factors. Memory functions (short-term, super- and
      long-term spans) for different stimuli types (verbal and visual) were evaluated
      using Visual Auditory Digit Span tasks (VADS), Rey Auditory Verbal Learning Test
      (Rey-AVLT), and Rey Osterrieth Complex Figure Test (ROCF). RESULTS: Children with
      IUGR had short-term memory difficulties that hindered both serial verbal
      processing system and simultaneous processing of high-load visuo-spatial stimuli.
      The difficulties were not related to prematurity, neonatal complications or
      growth catch-up, but were augmented by lower maternal education. Recognition
      skills and benefits from reiteration, typically affected by hippocampal
      dysfunction, were preserved in both groups. CONCLUSIONS: Memory profile of
      children born with IUGR is characterized primarily by a short-term memory deficit
      that does not necessarily comply with a typical hippocampal deficit, but rather
      may reflect an executive short-term memory deficit characteristic of anterior
      hippocampal-prefrontal network. Implications for cognitive intervention are
      discussed.

PMID- 16962083
TI  - Osteopontin expression in substantia nigra in MPTP-treated primates and in
      Parkinson's disease.
AB  - Parkinson's disease (PD) is characterised by the loss of dopaminergic neurones in
      the substantia nigra (SN) but the pathogenic mechanism remains unknown. Cell
      death involves oxidative stress and inflammatory mechanisms, and these may be
      altered by the actions of the glycosylated phosphoprotein osteopontin (OPN). OPN
      is present in the rat SN, but its presence in human and non-human primate brain
      has not been extensively studied. Both OPN mRNA and protein were present in the
      normal marmoset SN, and OPN protein was localised to nigral neurones although
      these were not dopaminergic cells and it was not present in glial cells. In
      contrast, OPN protein was found in dopaminergic neurones in the normal human SN
      but again not in glial cells with some accumulation in the extracellular matrix.
      Following MPTP treatment of common marmosets, OPN protein expression was
      decreased, although its mRNA levels were unchanged and it was not present in
      either activated microglia or astrocytes. In the SN in PD, OPN protein expression
      was decreased in the remaining dopaminergic neurones and it was present in
      activated microglia but not in astrocytes. This was not specific to PD as OPN
      protein expression was also decreased in the SN in multiple system atrophy and
      progressive supranuclear palsy with an identical localisation of the protein. The
      presence of OPN in the normal human and non-human primate SN coupled to its
      decreased expression following nigral cell degeneration suggests that it may play
      an important role in dopaminergic neurone survival.

PMID- 16962084
TI  - The glass transition temperatures of sugar mixtures.
AB  - We measured the glass transition temperatures of mono-, di-, and trisaccharide
      mixtures using differential scanning calorimeter (DSC) and analyzed these
      temperatures using the Gordon-Taylor equation. We found that the glass transition
      temperatures of monosaccharide-monosaccharide and disaccharide-disaccharide
      mixtures could be described by the conventional Gordon-Taylor equation. However,
      the glass transition temperatures of monosaccharide-disaccharide and
      monosaccharide-trisaccharide mixtures deviated from the conventional Gordon
      Taylor equation and the amount of deviation in the monosaccharide-trisaccharide
      mixtures was larger than those in the monosaccharide-disaccharide mixtures. From
      these results, we conclude that the size and shape of the sugars play an
      important role in the glass transition temperature of the mixtures.

PMID- 16962085
TI  - Mechanical stress enhances serotonin 2B receptor modulating brain natriuretic
      peptide through nuclear factor-kappaB in cardiomyocytes.
AB  - OBJECTIVE: Serotonin via serotonin 2B receptors (SR2BR) regulates cardiac
      embryonic development and adult heart functions. However, the role of SR2BR in
      the failing heart due to pressure overload is not well understood. METHODS:
      Wistar rats of aortic banding and neonatal cardiomyocyte with mechanical stretch
      were used as cardiomyopathy models. RESULTS: After two weeks of aortic banding
      surgery, serum serotonin, mRNA and protein expression of SR2BR increased
      significantly. The selective SR2BR antagonist, SB215505 (SB), significantly
      reduced the increase in heart weight, decreased heart wall thickness, left
      ventricular mass and the expression of the brain natriuretic peptide (BNP) but
      did not attenuate the up-regulation of SR2BR protein expression in rats after
      aortic banding for three weeks. After following in vitro mechanical stretch of
      cardiomyocytes and incubation with serotonin 1 muM, the level of SR2BR and BNP
      protein increased time-dependently. When transfected by specific siRNA of SR2BR
      or pretreated with caffeic acid phenethyl ester in cardiomyocytes, the increase
      of nuclear factor-kappaB (NF-kappaB) translocation and BNP protein induced by
      serotonin incubation plus mechanical stretch were both reversed. CONCLUSIONS:
      SR2BR expression is involved in pressure-induced cardiomyopathy and its
      downstream signaling may involve NF-kappaB to modulate BNP expression in
      cardiomyocyte.

PMID- 16962086
TI  - The role of the anticancer drug vinorelbine in lipid bilayers using differential
      scanning calorimetry and molecular modeling.
AB  - Differential scanning calorimetry (DSC) has been employed to investigate the
      thermal changes caused by the anticancer alkaloid drug vinorelbine in
      dipalmytoylphosphatidylcholine (DPPC) bilayers. The total enthalpy change was
      increased by the presence of the drug molecule, indicating a partial
      interdigitation of the lipid alkyl chains. The presence of cholesterol in DPPC
      bilayers including vinorelbine induced an obstruction of the interdigitation,
      since cholesterol interrupts the upraise of enthalpy change. Vinorelbine's
      interdigitation ability and stabilizing properties with the active site of the
      receptor have been compared with those of similar in structure amphipathic and
      bulky alkaloid vinblastine. The obtained results may in part explain their
      similar mechanism of action but different bioactivity.

PMID- 16962087
TI  - Association of human serum apolipoprotein A5 with lipid profiles affected by
      gender.
AB  - BACKGROUND: Apolipoprotein A5 (ApoA5) is present in human serum at a very low
      concentration. We developed a new method to determine ApoA5 concentration in
      human serum, and to investigate the correlation between serum ApoA5 and the lipid
      profiles in healthy subjects, and to analyze whether the correlation was affected
      by gender. METHODS: All the subjects (total 92, male 50, female 42) were healthy
      subjects without any medication. Lipids were measured enzymatically. An ELISA
      performed by a couple of monoclonal antibodies was used to measure serum ApoA5.
      RESULTS: The average ApoA5 concentration was 182.7+/-104.7 ng/ml ranging from 5.4
      to 455.6 ng/ml. Serum ApoA5 concentration was negatively correlated with TG in
      female (r=-0.496, P=0.001). In all subjects, ApoA5 concentration was positively
      correlated to HDL-C (r=0.453, P<0.001). This correlation was more predominant in
      female (r=0.617, P<0.001) than in male (r=0.289, P=0.042). ApoA5 concentration
      was negatively correlated to body mass index (BMI) with more significance in
      female than in male (r=-0.345, P=0.001 for all; r=-0.456, P=0.002 for female; r=
      0.198, P=0.167 for male). CONCLUSIONS: The serum concentration of ApoA5 was very
      low. The concentration of ApoA5 was negatively correlated with TG and BMI, but
      positively correlated with HDL-C. The correlations were affected by gender.

PMID- 16962088
TI  - Identification of N-ethylglycine in urine of cancer patients with metastatic bone
      disease.
AB  - BACKGROUND: Previously, a HPLC method for the determination of N-terminal prolyl
      dipeptides, proline and hydroxyproline in urine with fluorescence detection after
      pre-column derivatization with 4-(5,6-dimethoxy-2-phthalimidinyl)-2
      methoxyphenylsulfonyl chloride (DMS-Cl) [Inoue H, Iguchi H, Kono A, Tsuruta Y.
      Highly sensitive determination of N-terminal prolyl dipeptides, proline and
      hydroxyproline in urine by high-performance liquid chromatography using a new
      fluorescent labelling reagent, 4-(5,6-dimethoxy-2-phthalimidinyl)-2
      methoxyphenylsulfonyl chloride. J Chromatogr 1999;724:221-230] was developed to
      study the relation between those analytes and bone diseases. When the urinary
      analytes were measured, a large peak due to an unknown substance was recognized
      in the chromatograms of cancer patients with metastatic bone disease, although it
      was scarcely present in normal subjects. In this study, we identified the unknown
      substance. METHODS: The fluorescent fraction based on the unknown substance was
      collected using HPLC and the structure of the fluorescence product was analyzed
      with MS, (1)H NMR and (13)C NMR. RESULTS: The fluorescence product based on the
      unknown substance was established to be a DMS-derivative of N-ethylglycine.
      CONCLUSIONS: Excretion of N-ethylglycine in the urine of cancer patients with
      metastatic bone disease is recognized, although N-ethylglycine is scarcely
      excreted in the urine of normal subjects.

PMID- 16962089
TI  - Elevated hair levels of cadmium and lead in school children exposed to smoking
      and in highways near schools.
AB  - OBJECTIVES: Heavy metal pollution has become a serious health concern in recent
      years. Cadmium (Cd) and Lead (Pb) are toxic heavy metals. This study was aimed to
      determine the risk factors for high cadmium and lead levels in school children.
      DESIGN AND METHODS: The scalp hair samples were obtained from 760 children at 13
      schools in Istanbul. A questionnaire was prepared to gather information about
      demographic and socioeconomic characteristics of the children. Hair cadmium and
      lead concentrations were determined by atomic absorption spectrophotometer.
      RESULTS: Household exposure to smoking and attending a school near to Main
      Streets were found to be the most important risk factors for the high hair
      cadmium and lead levels in our study. CONCLUSION: These findings support the
      public health recommendations that children should not have household exposure to
      smoking, schools should not be near to the main streets and unleaded gasoline use
      should be promoted.

PMID- 16962090
TI  - Reading ability is negatively related to Stroop interference.
AB  - Stroop interference is often taken as evidence for reading automaticity even
      though young and poor readers, who presumably lack reading automaticity, present
      strong interference. Here the relationship between reading skills and Stroop
      interference was studied in a 7th-grade sample. Greater interference was observed
      in children diagnosed with reading disability (dyslexia) than in unimpaired
      children. Moreover, poorer reading skills were found to correlate with greater
      Stroop interference in the general school population. In correlation and
      regression analyses, interference was primarily associated with reading speed,
      with an additional unique contribution of reading accuracy. Color naming errors
      were few and not comparably related to reading skills. The relation of reading
      skill to Stroop interference was examined in computational modeling simulations.
      The production model of Roelofs [Roelofs, A. (2003). Goal-referenced selection of
      verbal action: modeling attentional control in the Stroop task. Psychological
      Review, 110, 88-125], in which interference is primarily due to word stimuli
      having direct access to word form encoding whereas color naming must pass through
      concept activation and lemma selection, was found to account well for the human
      data after imposing covariation constraints on parameters controlling word
      processing and blocking latency, in modifications not affecting the model's
      previous fit to other data. The connectionist model of Cohen, Dunbar, and
      McClelland [Cohen, J. D., Dunbar, K., & McClelland, J. L. (1990). On the control
      of automatic processes: a parallel distributed processing account of the Stroop
      effect. Psychological Review, 97, 332-361], in which interference is caused by
      differential route strength, implementing an automaticity account, approximated
      the observed patterns with network-wide parameter manipulations not specific to
      reading, such as processing speed and response threshold, likely to affect
      previously optimized performance. On the basis of the empirical and modeling data
      we argue for a direct link between reading skill and interference, beyond the
      effects of executive functioning.

PMID- 16962091
TI  - Patterns and trends in sediment toxicity in the San Francisco Estuary.
AB  - Widespread sediment toxicity has been documented throughout the San Francisco
      Estuary since the mid-1980s. Studies conducted in the early 1990s as part of the
      Bay Protection and Toxic Cleanup Program (BPTCP), and more recently as part of
      the Regional Monitoring Program (RMP) have continued to find sediment toxicity in
      the Estuary. Results of these studies have shown a number of sediment toxic
      hotspots located at selected sites in the margins of the Estuary. Recent RMP
      monitoring has indicated that the magnitude and frequency of sediment toxicity is
      greater in the winter wet season than in the summer dry season, which suggests
      stormwater inputs are associated with sediment toxicity. Additionally, spatial
      trends in sediment toxicity data indicate that toxic sediments are associated
      with inputs from urban creeks surrounding the Estuary, and from Central Valley
      rivers entering the northern Estuary via the Delta. Sediment toxicity has been
      correlated with a number of contaminants, including selected metals, PAHs and
      organochlorine pesticides. While toxicity identification evaluations (TIEs)
      suggest that metals are the primary cause of sediment toxicity to bivalve
      embryos; TIEs conducted with amphipods have been inconclusive.

PMID- 16962092
TI  - Characterization of the antinociceptive and anti-inflammatory activities of
      riboflavin in different experimental models.
AB  - Riboflavin, similar to other vitamins of the B complex, presents anti
      inflammatory activity but its full characterization has not yet been carried out.
      Therefore, we aimed to investigate the effect of this vitamin in different models
      of nociception, edema, fever and formation of fibrovascular tissue. Riboflavin
      (25, 50 or 100 mg/kg, i.p.) did not alter the motor activity of mice in the rota
      rod or the open field models. The second phase of the nociceptive response
      induced by formalin in mice was inhibited by riboflavin (50 or 100 mg/kg). The
      first phase of this response and the nociceptive behavior in the hot-plate model
      were inhibited only by the highest dose of this vitamin. Riboflavin (25, 50 or
      100 mg/kg, i.p.), administered immediately and 2 h after the injection of
      carrageenan, induced antiedema and antinociceptive effects. The antinociceptive
      effect was not inhibited by the pretreatment with cadmium sulfate (1 mg/kg), an
      inhibitor of flavokinase. Riboflavin (50 or 100 mg/kg, i.p., 0 and 2 h) also
      inhibited the fever induced by lipopolysaccharide (LPS) in rats. Moreover, the
      formation of fibrovascular tissue induced by s.c. implant of a cotton pellet was
      inhibited by riboflavin (50 or 100 mg/kg, i.p., twice a day for one week).
      Riboflavin (10 or 25 mg/kg, i.p.) also exacerbated the effect of morphine (2, 4
      or 8 mg/kg, i.p.) in the mouse formalin test. In conclusion, the study
      demonstrates the antinociceptive and anti-inflammatory activities of riboflavin
      in different experimental models. These results, associated with the fact that
      riboflavin is a safe drug, is approved for clinical use and exacerbates the
      antinociceptive effect of morphine, may warrant clinical trials to assess its
      potential in the treatment of different painful or inflammatory conditions.

PMID- 16962093
TI  - Comparison between effects of intravenous and nebulized histamine in guinea pigs:
      correlation between changes in respiratory mechanics and exhaled nitric oxide.
AB  - Nitric oxide (NO) is a marker of airway inflammation in humans, despite not
      having effects on basal bronchial tone. Inhibition of NO synthesis can lead to
      enhanced airway reactivity in humans and it is therefore of importance to
      understand how bronchial provocation can affect endogenous NO. Presently, we have
      studied the role of exhaled nitric oxide in airway reactivity by measuring
      changes in pulmonary mechanics in response to histamine in anaesthetized guinea
      pigs. Two groups were challenged i.v. and four groups were challenged by aerosol
      at different doses. One of the i.v. and one of the aerosol groups received an
      inhibitor of NO synthesis, N(omega)-nitro-L-arginine methyl ester (L-NAME), to
      reduce endogenous production of NO before histamine challenge. All animals with
      intact NO production showed a decrease in exhaled nitric oxide after challenge.
      There were positive correlations between the peak in exhaled nitric oxide and
      pulmonary resistance, and between the decrease in exhaled nitric oxide and lung
      compliance. L-NAME pretreatment increased the reactivity to aerosolized histamine
      but not to i.v. histamine. We conclude that the different ways of administration
      elicit different response patterns of exhaled nitric oxide, resistance, and
      compliance, even when compared at similar insufflation pressure changes. The
      effects of L-NAME suggest that, although different mechanisms might be
      responsible for the changes in pulmonary mechanics, inhibition of endogenous NO
      enhances decrements in pulmonary function when histamine is administered in an
      aerosol. The close relationship between changes in exhaled nitric oxide and
      changes in lung compliance and pulmonary resistance merits further studies on the
      relationship between NO and airway reactivity.

PMID- 16962094
TI  - Molecular interactions with obscurin are involved in the localization of muscle
      specific small ankyrin1 isoforms to subcompartments of the sarcoplasmic
      reticulum.
AB  - We report here on experiments aimed to characterise the molecular basis of the
      interactions between muscle-specific ankyrin1 isoforms localized on the
      sarcoplasmic reticulum and obscurin a protein associated with the contractile
      apparatus. A novel small muscle-specific ankyrin isoform, ank1.9 was identified
      that, similarly to the known ank1.5 isoform, was able to bind to obscurin in
      yeast two-hybrid assay and in pull-down experiments. Two distinct binding sites
      in the C-terminus of obscurin were found to mediate binding with ank1.5 and
      ank1.9. Interactions between ank1.5 and ank1.9 with recombinant proteins
      containing one or two of the binding sites of obscurin were confirmed by
      expressing recombinant proteins in NIH3T3 cells. In cultured myotubes, ank1.5 and
      ank1.9 colocalized with endogenous obscurin at the M-band region. In contrast
      with evidence of efficient binding between small ank1 isoforms and obscurin, in
      vitro interaction studies and transfection experiments in myotubes indicated that
      small ank1 isoforms do not efficiently interact with titin. Altogether, these
      results support a role of obscurin in mediating the subcellular localization of
      small ank1 isoforms in striated muscle cells. Given that the localization of
      small muscle-specific ank1 isoforms mirrors that of obscurin, we propose that
      obscurin and small ank1 isoforms may form stable interactions that may be
      relevant to connect the sarcoplasmic reticulum and the contractile apparatus in
      skeletal muscle cells.

PMID- 16962096
TI  - Identification of the Drosophila skpA gene as a novel target of the transcription
      factor DREF.
AB  - SKPa is component of a Drosophila SCF complex that functions in combination with
      the ubiquitin-conjugating enzyme UbcD1. skpA null mutation results in centrosome
      overduplication, unusual chromatin condensation, defective endoreduplication and
      cell-cycle progression. While the molecular mechanisms that regulate expression
      of the skpA gene are poorly understood, the DNA replication-related element (DRE)
      and the DRE-binding factor (DREF) play important roles in regulating
      proliferation-related genes in Drosophila and DRE (5'-TATCGATA) and DRE-like (5'
      CATCGATT) sequences were here found to be involved in skpA promoter activity.
      Thus both luciferase transient expression assays in cultured Drosophila S2 cells
      using skpA promoter-luciferase fusion plasmids and anti-lacZ immunostaining of
      various tissues from transgenic third instar larvae carrying the skpA promoter
      lacZ fusion genes provided supportive evidence. Furthermore, anti-SKPa
      immunostaining of eye imaginal discs from flies overexpressing DREF showed
      ectopic expression of protein in the region posterior to the morphogenetic furrow
      where DREF is overexpressed. Knockdown of DREF in some tissues where SKPa
      distribution is well known almost completely abrogated the skpA gene expression.
      These findings, taken together, indicate that the Drosophila skpA gene is a novel
      target of the transcription factor DREF.

PMID- 16962095
TI  - Molecular basis for the redox control of nuclear transport of the structural
      chromatin protein Hmgb1.
AB  - Oxidative stress can induce a covalent disulfide bond between protein and peptide
      thiols that is reversible through enzymatic catalysis. This process provides a
      post-translational mechanism for control of protein function and may also protect
      thiol groups from irreversible oxidation. High mobility group protein B1 (Hmgb1),
      a DNA-binding structural chromosomal protein and transcriptional co-activator was
      identified as a substrate of glutaredoxin. Hmgb1 contains 3 cysteines, Cys23, 45,
      and 106. In mild oxidative conditions, Cys23 and Cys45 readily form an
      intramolecular disulfide bridge, whereas Cys106 remains in the reduced form. The
      disulfide bond between Cys23 and Cys45 is a target of glutathione-dependent
      reduction by glutaredoxin. Endogenous Hmgb1 as well as GFP-tagged wild-type Hmgb1
      co-localize in the nucleus of CHO cells. While replacement of Hmgb1 Cys23 and/or
      45 with serines did not affect the nuclear distribution of the mutant proteins,
      Cys106-to-Ser and triple cysteine mutations impaired nuclear localization of
      Hmgb1. Our cysteine targeted mutational analysis suggests that Cys23 and 45
      induce conformational changes in response to oxidative stress, whereas Cys106
      appears to be critical for the nucleocytoplasmic shuttling of Hmgb1.

PMID- 16962097
TI  - Inhibition of Aurora kinases perturbs chromosome alignment and spindle checkpoint
      signaling in rat spermatocytes.
AB  - In somatic cells, integrity of cell division is safeguarded by the spindle
      checkpoint, a signaling cascade that delays the separation of sister chromatids
      in the presence of misaligned chromosomes. Aurora kinases play important roles in
      this process by promoting centrosome maturation, chromosome bi-orientation,
      spindle checkpoint signaling, and cytokinesis. To investigate the functions of
      Aurora kinases in male meiosis, we applied a small molecule Aurora inhibitor,
      ZM447439, to seminiferous tubules in vitro. Primary and secondary spermatocytes
      exposed to ZM447439 exhibit defects in the spindle morphology and fail to align
      their chromosomes at the metaphase plate. Moreover, the treated spermatocytes
      undergo a forced exit from the meiotic M-phase without cytokinesis. These results
      suggest that the activities of Aurora kinases are required for normal spindle
      assembly as well as for establishment and maintenance of proper microtubule
      kinetochore attachments and spindle checkpoint signaling in male mammalian
      meiosis.

PMID- 16962098
TI  - Induced cerebral hypothermia reduces post-hypoxic loss of phenotypic striatal
      neurons in preterm fetal sheep.
AB  - Perinatal hypoxic-ischemic injury of the basal ganglia is a significant cause of
      disability in premature infants. Prolonged, moderate cerebral hypothermia has
      been shown to be neuroprotective after experimental hypoxia-ischemia; however, it
      has not been tested in the preterm brain. We therefore examined the effects of
      severe hypoxia and the potential neuroprotective effects of delayed hypothermia
      on phenotypic striatal neurons. Preterm (0.7 gestation) fetal sheep received
      complete umbilical cord occlusion for 25 min followed by cerebral hypothermia
      (fetal extradural temperature reduced from 39.4+/-0.3 degrees C to 29.5+/-2.6
      degrees C) from 90 min to 70 h after the end of occlusion. Hypothermia was
      associated with a significant overall reduction in striatal neuronal loss
      compared with normothermia-occlusion fetuses (mean+/-SEM, 5.5+/-1.2% vs. 38.1+/
      6.5%, P<0.01). Immunohistochemical studies showed that occlusion resulted in a
      significant loss of calbindin-28 kd, glutamic acid decarboxylase isoform 67 and
      neuronal nitric oxide synthase-immunopositive neurons (n=7, P<0.05), but not
      choline acetyltransferase-positive neurons, compared with sham controls (n=7).
      Hypothermia (n=7) significantly reduced the loss of calbindin-28 kd and neuronal
      nitric oxide synthase, but not glutamic acid decarboxylase-immunopositive
      neurons. In conclusion, delayed, prolonged moderate head cooling was associated
      with selective protection of particular phenotypic striatal projection neurons
      after severe hypoxia in the preterm fetus. These findings suggest that head
      cooling may help reduce basal ganglia injury in some premature babies.

PMID- 16962099
TI  - Compound action potential of sensory tail nerves in the rat.
AB  - Assessment of the conduction velocity of motor fibers of the rat tail nerves has
      been used by some authors in the past, but very little is known about the sensory
      fibers. In 10 adult rats, weighing between 320 and 380 g, responses from the
      nerves and muscles of the tail have been recorded after stimulation at its root
      and tip. It was found that stimulation of the tip involved mainly sensory fibers,
      of which two main groups could be identified. One faster group, conducting within
      the range of 38-27 m/s, and one slower group with range 14-7 m/s. The bipolar
      recording configuration was found to be optimal for sensory recording.
      Stimulation of the tail root evoked a motor response, which was preceded by a
      very small neurographic activity, due to the fastest sensory fibers conducting
      antidromically. The conduction velocity of motor fibers was calculated to be
      approximately 19 m/s. Distance traveled by the volley can be assessed with
      excellent precision on the tail nerves; hence the calculated conduction
      velocities are highly reliable and reproducible. We propose that the tail nerves
      may be a useful tool for evaluation of conduction velocity of Abeta and Adelta
      afferents. As the technique is just minimally invasive, the test can be repeated
      a number of times in animals under chronic experimental conditions.

PMID- 16962101
TI  - Epidermal sphingolipids: metabolism, function, and roles in skin disorders.
AB  - Mammalian epidermis produces and delivers large quantities of glucosylceramide
      and sphingomyelin precursors to stratum corneum extracellular domains, where they
      are hydrolyzed to corresponding ceramide species. This cycle of lipid precursor
      formation and subsequent hydrolysis represents a mechanism that protects the
      epidermis against potentially harmful effects of ceramide accumulation within
      nucleated cell layers. Prominent skin disorders, such as psoriasis and atopic
      dermatitis, have diminished epidermal ceramide levels, reflecting altered
      sphingolipid metabolism, that may contribute to disease severity/progression.
      Enzymatic processes in the hydrolysis of glucosylceramide and sphingomyelin, and
      the roles of sphingolipids in skin diseases, are the focus of this review.

PMID- 16962100
TI  - Acetaldehyde promotes rapamycin-dependent activation of p70(S6K) and glucose
      uptake despite inhibition of Akt and mTOR in dopaminergic SH-SY5Y human
      neuroblastoma cells.
AB  - Alcohol intake is one of the important lifestyle factors for the risk of insulin
      resistance and type 2 diabetes. Acetaldehyde, the major ethanol metabolite which
      is far more reactive than ethanol, has been postulated to participate in alcohol
      induced tissue injury although its direct impact on insulin signaling is unclear.
      This study was designed to examine the effect of acetaldehyde on glucose uptake
      and insulin signaling in human dopaminergic SH-SY5Y cells. Akt, mammalian target
      of rapamycin (mTOR), ribosomal-S6 kinase (p70(S6K)), the eukaryotic translation
      initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) and insulin receptor
      substrate (IRS)-2 were evaluated by Western blot analysis. Glucose uptake and
      apoptosis were measured using [(3)H]-2-deoxyglucose uptake and caspase-3 assay,
      respectively. Short-term exposure (12 h) of acetaldehyde (150 muM) facilitated
      glucose uptake in a rapamycin-dependent manner without affecting apoptosis, IRS-2
      expression and insulin-stimulated glucose uptake in SH-SY5Y cells. Acetaldehyde
      suppressed basal and insulin-stimulated Akt phosphorylation without affecting
      total Akt expression. Acetaldehyde inhibited mTOR phosphorylation without
      affecting total mTOR and insulin-elicited response on mTOR phosphorylation.
      Rapamycin, which inhibits mTOR leading to inactivation of p70(S6K), did not
      affect acetaldehyde-induced inhibition on phosphorylation of Akt and mTOR.
      Interestingly, acetaldehyde enhanced p70(S6K) activation and depressed 4E-BP1
      phosphorylation, the effect of which was blunted and exaggerated, respectively,
      by rapamycin. Collectively, these data suggested that acetaldehyde did not
      adversely affect glucose uptake despite inhibition of insulin signaling cascade
      at the levels of Akt and mTOR, possibly due to presence of certain mechanism(s)
      responsible for enhanced p70(S6K) phosphorylation.

PMID- 16962102
TI  - Normal mode analysis as a prerequisite for drug design: application to matrix
      metalloproteinases inhibitors.
AB  - We demonstrate the utility of normal mode analysis in correctly predicting the
      binding modes of inhibitors in the active sites of matrix metalloproteinases
      (MMPs). We show the accuracy in predicting the positions of MMP-3 inhibitors is
      strongly dependent on which structure is used as the target, especially when it
      has been energy minimized. This dependency can be overcome by using intermediate
      structures generated along one of the normal modes previously calculated for a
      given target. These results may be of prime importance for further in silico drug
      discovery.

PMID- 16962103
TI  - Dammarenediol-II synthase, the first dedicated enzyme for ginsenoside
      biosynthesis, in Panax ginseng.
AB  - Panax ginseng produces triterpene saponins called ginsenosides, which are
      classified into two groups by the skeleton of aglycones, namely dammarane type
      and oleanane type. Dammarane-type ginsenosides dominate over oleanane type not
      only in amount but also in structural varieties. However, their sapogenin
      structure is restricted to two aglycones, protopanaxadiol and protopanaxatriol.
      So far, the genes encoding oxidosqualene cyclase (OSC) responsible for formation
      of dammarane skeleton have not been cloned, although OSC yielding oleanane
      skeleton (beta-amyrin synthase) has been successfully cloned from this plant. In
      this study, cDNA cloning of OSC producing dammmarane triterpene was attempted
      from hairy root cultures of P. ginseng by homology based PCR method. A new OSC
      gene (named as PNA) obtained was expressed in a lanosterol synthase deficient
      (erg7) Saccharomyces cerevisiae strain GIL77. LC-MS and NMR analyses identified
      the accumulated product in the yeast transformant to be dammarenediol-II,
      demonstrating PNA to encode dammarenediol-II synthase.

PMID- 16962104
TI  - A proposed model of fat packaging by exchangeable lipid droplet proteins.
AB  - Humans have evolved mechanisms of efficient fat storage to survive famine, but
      these mechanisms contribute to obesity in our current environment of plentiful
      food and reduced activity. Little is known about how animals package fat within
      cells. Five related structural proteins serve roles in packaging fat into lipid
      droplets. The proteins TIP47, S3-12, and OXPAT/MLDP/PAT-1 move from the cytosol
      to coat nascent lipid droplets during rapid fat storage. In contrast, perilipin
      and adipophilin constitutively associate with lipid droplets and play roles in
      sustained fat storage and regulation of lipolysis. Different tissues express
      different complements of these lipid droplet proteins. Thus, the tissue-specific
      complement of these proteins determines how tissues manage lipid stores.

PMID- 16962105
TI  - C-reactive protein inhibits in vitro oxidation of low-density lipoprotein.
AB  - C-reactive protein (CRP) is elevated in cardiovascular disease and binds to
      oxidized phosphatidylcholine (oxPtC) in the low-density lipoprotein (LDL)
      surface. In the present study, we tested if CRP influences the susceptibility of
      LDL to oxidation. At physiological concentrations of 1-7mug/ml, CRP strongly
      inhibited copper-mediated oxidation of LDL and phospholipid liposomes in a
      concentration-dependent manner. Similar concentrations of different monoclonal
      antibodies or albumin did not influence LDL oxidation. Antioxidant activity of
      CRP was inhibited by phosphocholine (PC), indicating that the observed activity
      involves binding of CRP to oxPtC. These results suggest that CRP may limit
      atherogenic oxidation of LDL in vivo.

PMID- 16962106
TI  - Cumulus coculture and cumulus-aided embryo transfer increases pregnancy rates in
      patients undergoing in vitro fertilization.
AB  - OBJECTIVE: To evaluate the effect of the use of cumulus-aided embryo transfer on
      pregnancy rates. To study the proximity of expanded cumulus cells to the
      developing embryo. To document by light microscopy the anchoring of day 3 to day
      4 embryos by the expanded cumulus cells. To demonstrate by transmission electron
      microscopy the cellular activity of the expanded cumulus cells. To evaluate the
      expression of growth factors (vascular endothelial growth factor, interleukin-6,
      insulin-like growth factor I) that are secreted by the cumulus cells. DESIGN: A
      comparative study of a group of women undergoing cumulus coculture and cumulus
      aided embryo transfer, with those who underwent cumulus coculture but did not
      undergo cumulus-aided embryo transfer. The endpoint was the achievement of
      pregnancy. SETTING: Department of Infertility Management and Assisted
      Reproduction, Jaslok Hospital and Research Centre, Mumbai, India. PATIENT(S):
      Five hundred seventeen women undergoing treatment for infertility using
      intracytoplasmic sperm injection and embryo transfer and fulfilling set criteria.
      To validate our initial results, we conducted a similar study on 208 women where
      randomization was performed. INTERVENTION(S): Embryos were cocultured with the
      patient's own cumulus cells and were transferred into the uterus with
      approximately 30 microL of the expanded cumulus cells. MAIN OUTCOME MEASURE(S):
      Pregnancy, implantation, and multiple gestation rates. RESULT(S): Our study
      demonstrated a significant increase in the implantation rate in the study group
      (group A) of 25.6% versus 14.5% in the control group (group B) and a significant
      increase in the pregnancy rate in the study group (group A) of 47.6% versus 34%
      achieved in the control group (group B). Although the incidence of multiple
      gestation was similar (38.6% in the study group and 32.9% in the control group),
      the higher-order multiple gestation rate was significantly more in the study
      group as compared with the control group (18.1% vs. 2.4%). Similar pregnancy and
      implantation rates were observed in the randomized study. CONCLUSION(S): This
      study demonstrates the efficacy of cumulus-aided embryo transfer, using
      autologous cumulus cells. It indicates a significant increase in implantation and
      pregnancy rates. The results suggest that cumulus cells play an important role in
      embryonic development, and that they may provide a mechanism to improve embryo
      uterine adhesion by physical proximity, and by secreting cytokines and growth
      factors required to aid the implantation process.

PMID- 16962107
TI  - Aberrant expression of apoptosis proteins and ultrastructural aberrations in
      uterine leiomyomas from patients with hereditary leiomyomatosis and renal cell
      carcinoma.
AB  - OBJECTIVE: To examine differences between sporadic and familial uterine
      leiomyomata related to expression of apoptosis-related proteins and tumor
      ultrastructure. DESIGN: Expression of apoptosis-related proteins was measured by
      immunohistochemistry. Tumor ultrastructure was evaluated by transmission electron
      microscopy. SETTING: Human genetics laboratory. PATIENT(S): Patients confirmed
      for hereditary leiomyomatosis and renal cell carcinoma (HLRCC), and anonymous
      archival sporadic leiomyoma patients. INTERVENTION(S): Samples for electron
      microscopy were collected from myomectomy and hysterectomy with informed consent.
      Other samples were archival. MAIN OUTCOME MEASURE(S): Intensity of
      immunohistochemistry staining and evaluation of electron micrographs. RESULT(S):
      Immunohistochemistry revealed increases in expression of antiapoptotic Bcl-2 and
      the proliferation factor proliferating cell nuclear antigen (PCNA) in both
      sporadic and HLRCC uterine leiomyomata. Furthermore, we observed an increase in
      antiapoptotic Bcl-x and a concurrent decrease in proapoptotic Bak solely in HLRCC
      leiomyomas. We also observed ultrastructural alterations in HLRCC and sporadic
      leiomyomas, particularly pertaining to extracellular matrix and intermediate
      filament aggregation. CONCLUSION(S): The observed alterations in expression of
      apoptosis-related proteins indicate a shift in both HLRCC and sporadic leiomyomas
      to increased resistance to apoptosis compared with myometrium, which appears to
      be stronger in HLRCC leiomyomas. The changes observed in HLRCC leiomyomas appear
      to be related to activation of the hypoxia pathways. The results suggest not only
      a partial overlap in the pathogenic mechanism of the two tumor types, but also
      intriguing differences.

PMID- 16962108
TI  - A selective cyclooxygenase-2 inhibitor suppresses the growth of endometriosis
      xenografts via antiangiogenic activity in severe combined immunodeficiency mice.
AB  - OBJECTIVE: To investigate the effects of a selective cyclooxygenase (COX)-2
      inhibitor on endometriosis xenografts in immunodeficient mice. DESIGN:
      Prospective placebo-controlled study. SETTING: An academic facility at a Japanese
      university graduate school of medicine. PATIENT(S): Eight human ovarian
      endometriomas from seven patients. ANIMAL(S): Twenty-three female severe combined
      immunodeficiency (SCID) mice. INTERVENTION(S): Human ovarian endometriomas were
      implanted into the peritonea of SCID mice. Vehicle alone or NS398 (a selective
      COX-2 inhibitor, 10 mg/kg of weight per day) were administered orally daily for
      56 days after implantation. Mice were killed on the 56th day. MAIN OUTCOME
      MEASURE(S): Change in explants size and immunohistochemical analyses to
      evaluating the proliferation index, apoptosis index, microvessel density, and
      labeling index assessing vascular endothelial growth factor and COX-2 expression
      by the endometriotic lesion. RESULT(S): NS398 significantly decreased implant
      size in comparison to vehicle alone (NS398 [medians, with range in brackets]:
      22.0% [19.0%-36.7%] vs. vehicle: 41.2% [31.0%-55.3%], P<.01). Microvessel density
      (85.3 per mm2 [53.9-157.0 per mm2] vs. 121.8 per mm2 [97.2-259.6 per mm2], P=.02)
      and the vascular endothelial growth factor (0.4 [0-1.1] vs. 0.6 [0.5-2.1], P=.03)
      and COX-2 (0.4 [0.4-0.5] vs. 0.6 [0.4-0.8], P=.03) labeling indices in stromal
      cells were significantly lower in the NS398 group than in the vehicle group.
      There were no differences in the proliferation or apoptosis indices between the
      two groups. CONCLUSION(S): Selective COX-2 inhibitors decreased the size of
      implants and effectively treated endometriosis.

PMID- 16962109
TI  - Ultrasonographic-guided embryo transfer does not enhance pregnancy rates compared
      with embryo transfer based on previous uterine length measurement.
AB  - OBJECTIVE: To compare pregnancy rates (PRs) after ultrasound-guided embryo
      transfer and embryo transfer based on ultrasonographic length measurement.
      DESIGN: Prospective intervention group combined with retrospective control group.
      SETTING: University fertility clinic. PATIENT(S): Patients undergoing IVF and
      intracytoplasmic sperm injection. INTERVENTION(S): Transabdominal
      ultrasonographic guidance at embryo transfer. MAIN OUTCOME MEASURE(S): Pregnancy
      and implantation rates. RESULT(S): In 367 ultrasound-guided embryo transfers
      clinical PR, ongoing PR, and implantation rate were 35.1%, 31.1%, and 24.3%,
      respectively. In 363 embryo transfers based on previous ultrasonographic length
      measurement, the rates were 33.9%, 29.5%, and 24.2%, respectively. There were no
      statistical significant differences between the groups. CONCLUSION(S):
      Ultrasonographic guidance does not show any benefit in terms of PR and
      implantation rate compared to previous ultrasonographic length measurement, an
      other precise and atraumatic transfer technique.

PMID- 16962110
TI  - Vascular endothelial growth factor and matrix metalloproteinase-2 expedite
      formation of endometriosis in the early stage ICR mouse model.
AB  - OBJECTIVE: To establish a mouse model for endometriosis and to evaluate roles of
      vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2)
      in the formation of disease. DESIGN: Experimental laboratory study. SETTING: A
      women's hospital in China. PATIENT(S) AND ANIMAL(S): Ten women with endometriosis
      and 10 control women, as well as ICR mice. INTERVENTION(S): Endometrial fragments
      were transplanted in the peritoneal cavities of mice at minilaparotomy.
      Transplants were observed and then removed for the assessment of morphology and
      immunohistochemical staining of VEGF and MMP-2. MAIN OUTCOME MEASURE(S):
      Observation of transplants, expression of VEGF and MMP-2. RESULT(S): On days 1
      and 2, glandular and stromal cells were viable at the margins of transplants. On
      day 3, the transplants were surrounded by mesothelial cells, and the endometrial
      glands and stromal cells were clearly viable at the interface. The scores of VEGF
      and MMP-2 of viable glandular cells of transplants were increased compared with
      the ones before transplantation. The scores of VEGF and MMP-2 of transplants from
      women with endometriosis were higher than those of control women. CONCLUSION(S):
      Endometrial transplants from the patients with endometriosis express more VEGF
      and MMP-2 than endometrium in control women, suggesting that VEGF and MMP-2 may
      expedite the formation of endometriosis in its early stage.

PMID- 16962111
TI  - Role of cytosolic malate dehydrogenase in oocyte maturation and embryo
      development.
AB  - OBJECTIVE: To elucidate the function of cytosolic malate dehydrogenase (Mor2) in
      oocyte maturation and embryo development using RNA interference (RNAi). DESIGN:
      Experimental animal study. SETTING: Research unit of university. ANIMAL(S):
      Female 4-week-old (C57/BL6) mice. INTERVENTION(S): Isolation of immature germinal
      vesicle (GV) oocytes or fertilized pronucleus (PN) embryos, microinjection of
      Mor2 double-stranded RNA (dsRNA), and reverse transcription and polymerase chain
      reaction (RT-PCR) analysis to investigate Mor2-specific messenger RNA (mRNA)
      knockdown. MAIN OUTCOME MEASURE(S): Relative changes in mRNA levels after
      microinjection of Mor2 dsRNA and in rates of oocyte maturation and
      preimplantation embryo development. RESULT(S): Mor2 mRNA mostly was knocked down
      in germinal vesicle- and metaphase I (MI)-arrested oocytes, compared with
      metaphase II (MII)-developed oocytes, after microinjection of Mor2 dsRNA and in
      vitro culture for 16 hours. In vitro oocyte maturation was significantly
      decreased (34%), compared with noninjected (73.4%) and buffer-injected (67.5%)
      control groups. The rate of blastocyst development (48.1%) was lower in the Mor2
      dsRNA-injected group than in buffer-injected control (88.2%). CONCLUSION(S): In
      the present study, the function of Mor2 was analyzed with the aid of RNAi. On the
      basis of the data obtained, we propose that Mor2 is an essential factor for
      oocyte maturation and embryo development in mouse.

PMID- 16962112
TI  - Effects of hyperglycemia on the differential expression of insulin and insulin
      like growth factor-I receptors in human normal peritoneal and adhesion
      fibroblasts.
AB  - OBJECTIVE: To determine whether the insulin receptor (IR), insulin-like growth
      factor-I receptor (IGF-IR), and IGF-I are expressed differentially in fibroblasts
      isolated from normal peritoneal and adhesion tissue before and after 24-hour
      treatment with increasing glucose concentrations. DESIGN: Prospective
      experimental study. SETTING: University medical center. PATIENT(S): Primary
      cultures of fibroblasts established from peritoneal and adhesion tissues of the
      same patients. INTERVENTION(S): Glucose treatment of the primary cultured
      fibroblasts for 24 hours with increasing concentrations of glucose (100-850
      mg/dL). MAIN OUTCOME MEASURE(S): Real-time polymerase chain reaction was used to
      measure messenger RNA (mRNA) levels for IR, IGF-IR, and IGF-I. Enzyme-linked
      immunosorbent assay was used to determine protein levels. RESULT(S): At the
      normal glycemic level (100 mg/dL), adhesion fibroblasts have significantly higher
      mRNA levels of the IR (7.96 +/- 0.15 vs. 6.97 +/- 0.16; P<.05), IGF-IR (7.72 +/-
      0.22 vs. 6.88 +/- 0.06; P<.05), and IGF-I (7.04 +/- 0.10 vs. 5.92 +/- 0.10;
      P<.05) when compared with normal fibroblasts, respectively. Data are expressed as
      log(mRNA/microg RNA). Normal fibroblasts respond to increasing glucose
      concentrations by increasing the expression levels of the IR, IGF-IR, and IGF-I,
      whereas adhesion fibroblasts respond by decreasing the expression of the IR, IGF
      IR, and IGF-I. CONCLUSION(S): The differential expression of the IR, IGF-IR, and
      IGF-I in adhesion fibroblasts may contribute to the pathogenesis of fibrosis
      observed in diabetic patients.

PMID- 16962113
TI  - Management of hydrosalpinx before or during in vitro fertilization-embryo
      transfer: a national postal survey in France.
AB  - Using an anonymous and sealed questionnaire sent to all French IVF centers, the
      current management of hydrosalpinx before or during IVF was evaluated.
      Laparoscopic salpingectomy was recommended and undertaken in less than half of
      the centers, even though several other treatments were reported and despite
      medical evidence for this surgical option.

PMID- 16962114
TI  - Adenosine triphosphate synthesis, mitochondrial number and activity, and pyruvate
      uptake in oocytes after gonadotropin injections.
AB  - OBJECTIVE: To determine the effects of gonadotropin injection on the energy
      generation of mature oocytes. DESIGN: Randomized prospective study. SETTING:
      Gamete and stem cell biotechnology laboratory at Seoul National University in
      Korea. ANIMAL(S): Twelve- to 15-week-old golden hamsters (Mesocricetus auratus).
      INTERVENTION(S): Injections of pregnant mare serum gonadotropin (PMSG; 5 or 15
      IU), of hCG (5 or 15 IU), or of PMSG and hCG (15 IU of each; PMSG + hCG group)
      were administered to female hamsters. MAIN OUTCOME MEASURE(S): Adenosine
      triphosphate (ATP) synthesis, mitochondrial population number and activity, and
      pyruvate uptake were measured. RESULT(S): Significant (P<.05) differences were
      found in the ATP levels; compared with the control (no injection), a dramatic
      increase was detected after injections of 15 IU of hCG or of 15 IU of PMSG and 15
      IU of hCG. In the same treatments, the mitochondrial population (mitochondrial
      DNA copy number) significantly increased, whereas mitochondrial activity measured
      by the ratio of activated to less-activated mitochondria did not change. A
      significant increase in pyruvate uptake was detected after the injections of 15
      IU of PMSG and 15 IU of hCG. CONCLUSION(S): The change in ATP synthesis activity
      was a major cause for the adverse effect of gonadotropins on oocyte development
      in the hamster. The injections of 15 IU of hCG, or of 15 IU of PMSG and 15 IU of
      hCG, dramatically increased the ATP level, the mitochondrial population number,
      and pyruvate uptake.

PMID- 16962115
TI  - The association between menopausal symptoms and quality of life in midlife women.
AB  - This cross-sectional study examined 1,096 midlife women, associating menopausal
      symptoms, including hot flashes, vaginal dryness, sore joints, incontinence,
      irritability, mood changes, and headache, with quality of life (QOL), as measured
      using Cantril's Ladder of Life. The results showed that low QOL may be
      significantly associated with feeling tense and mood changes, but not the other
      selected symptoms.

PMID- 16962116
TI  - The clomiphene citrate challenge test for the prediction of poor ovarian response
      and nonpregnancy in patients undergoing in vitro fertilization: a systematic
      review.
AB  - OBJECTIVE: To systematically review the value of the clomiphene citrate challenge
      test (CCCT) in the prediction of poor ovarian response and pregnancy in IVF.
      DESIGN: Systematic review. SETTING: All studies that evaluated the CCCT in the
      prediction of poor ovarian response or pregnancy after IVF. PATIENT(S):
      Infertility population undergoing an IVF treatment. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Poor ovarian response, nonpregnancy. RESULT(S): From the
      literature we identified and analyzed 12 studies on the CCCT according to preset
      criteria. In predicting poor response, the sensitivity and specificity of the
      CCCT varied from 35% to 93% and 47% to 98%, respectively. In predicting
      nonpregnancy, the sensitivity and specificity varied from 13% to 66% and 73% to
      97%, respectively. Because of heterogeneity among studies, a summary receiver
      operating characteristics (ROC) curve could not be estimated. Back-to-back
      comparison of the CCCT with basal FSH was possible in six studies. In predicting
      poor response, the sensitivity of the CCCT increased to some extent, whereas
      specificity did not increase or even diminished. In predicting nonpregnancy, the
      CCCT also showed an increase in sensitivity, counteracted by a decrease in
      specificity. CONCLUSION(S): Summary estimates of test accuracy for the CCCT in
      IVF are not possible, because of heterogeneity among individual studies. A
      subanalysis of studies comparing basal FSH and the full CCCT showed that the CCCT
      has hardly any additional value.

PMID- 16962117
TI  - Prostaglandin-endoperoxide synthase (PTGS1 and PTGS2) expression and
      prostaglandin production by normal monkey ovarian surface epithelium.
AB  - OBJECTIVE: To determine whether hCG regulates the expression of prostaglandin
      (PG) synthesis enzymes and the production of PGs by normal monkey ovarian surface
      epithelium (OSE). DESIGN: Experimental animal study. SETTING: Research
      laboratory. ANIMAL(S): Adult cynomolgus macaques. INTERVENTION(S): Monkeys
      received exogenous gonadotropins to stimulate multiple follicular development.
      Ovarian surface epithelium cells and whole ovaries were obtained before (0 hours)
      and 36 hours after an ovulatory dose of hCG. MAIN OUTCOME MEASURE(S): Ovarian
      surface epithelium expression of prostaglandin-endoperoxide synthase 1 (PTGS1)
      and PTGS2 proteins was determined by immunocytochemistry. Prostaglandin synthesis
      enzyme messenger RNA (mRNA) levels were determined by RT-PCR. Prostaglandin E2
      and PGF2alpha production was assessed by enzyme immunoassays. RESULT(S): Ovarian
      surface epithelium maintained in long-term culture expressed mRNA and protein for
      PTGS1 and PTGS2 (n = 6); inhibition of PTGS1, but not PTGS2, reduced PGE2
      synthesis (n = 3). Prostaglandin-endoperoxide synthase 1 was present in OSE of
      ovarian tissue sections obtained 0 (n = 4) and 36 (n = 3) hours after hCG; PTGS2
      was not detected. Ovarian surface epithelium collected 0 (n = 3) and 36 (n = 4)
      hours after hCG expressed mRNAs for PTGS1, PTGS2, and three PGE synthases; the
      ratio of PTGS2 to PTGS1 increased in response to hCG exposure. CONCLUSION(S):
      Monkey OSE expresses mRNA for PTGS1, PTGS2, and all PGE synthases and produces
      PGE2 both before and 36 hours after hCG. Detection of PTGS1, but not PTGS2,
      protein in OSE in vivo supports the hypothesis that PTGS1 is the enzyme
      responsible for PGE2 production by primate OSE in vivo.

PMID- 16962118
TI  - In vitro blastocyst development from serially split mouse embryos and future
      implications for human assisted reproductive technologies.
AB  - OBJECTIVE: To assess the efficacy of serial splitting of mouse embryos with
      respect to blastocyst development. DESIGN: Prospective study. SETTING: Commercial
      research facility. ANIMAL(S): Commercially available mouse embryos from B6C3F-1 x
      B6D2F-1. INTERVENTION(S): One, two, and three blastomeres were biopsied from two
      , four-, and six-cell embryos, respectively, and were inserted into empty zona
      pellucida recipients (first split). These embryos were cultured to reach their
      original cell number status and then were split again (second split). Once these
      embryos regained their original cell status, they were split yet again (third
      split). MAIN OUTCOME MEASURE(S): Blastocyst development of embryos split serially
      at the two-, four-, and six-cell stages. RESULT(S): The blastocyst development
      rate for two-, four-, and six-cell embryos subjected to a first split was 74.3%,
      75.0%, and 66.6%, respectively, as compared with 71.8%, 62.6%, and 48.4% (second
      split) and 48.4%, 38.1%, and 10.6% (third split). CONCLUSION(S): First and second
      splitting of cleavage-stage embryos has yielded high efficiency rates for
      blastocyst development when compared with the third splitting, which did not
      provide any beneficial advantage for further embryo splitting and multiplication.
      This is the first study reporting on three serial embryo splittings in a
      mammalian species. Embryo splitting may have significant impact and applications
      in human assisted reproductive technology.

PMID- 16962119
TI  - Clomiphene citrate inhibits gonadotropin-induced ovulation by reducing cyclic
      adenosine 3',5'-cyclic monophosphate and prostaglandin E2 levels in rat ovary.
AB  - OBJECTIVE: To determine whether clomiphene citrate (CC) inhibited gonadotropin
      induced ovulation by reducing cyclic adenosine 3',5'-cyclic monophosphate (cAMP)
      and prostaglandin E2 (PGE2) levels in ovary. If so, to determine whether E2
      coadministration could protect against these effects of CC. DESIGN: A controlled
      prospective study. SETTING: Laboratory research setting in the department of
      reproductive biomedicine at a national research institute in India. ANIMAL(S):
      Sixty sexually immature female rats that were 24-25 days of age. INTERVENTION(S):
      The sexually immature female rats were given a single injection (10 IU i.m.) of
      pregnant mare serum gonadotropin. After 48 hours, the rats were given single
      injections of hCG (10 IU) along with CC, with or without E2, for 16 hours. MAIN
      OUTCOME MEASURE(S): Number of superovulated COCs, ovary and uterus weight, FSH
      and LH levels in serum, and cAMP and PGE2 levels in ovary. RESULT(S): The
      superovulatory dose of gonadotropins significantly increased ovary and uterus
      weights, cAMP and PGE2 levels in ovary, and serum levels of FSH and LH.
      Coadministration of CC (10 mg/kg body weight) significantly reduced levels of
      cAMP, PGE2 in the ovary, ovary and uterus weights, and ovulation rate, whereas
      FSH and LH levels were not significantly altered. Supplementation of E2 protected
      against these inhibitory effects of CC and augmented levels of FSH and LH in
      serum. CONCLUSION(S): Clomiphene citrate inhibited gonadotropin-induced ovulation
      by reducing cAMP and PGE2 levels in the ovary, and E2 protected against these
      effects of CC on gonadotropin-induced ovulation in rat.

PMID- 16962120
TI  - Opposing viscerovisceral effects of surgically induced endometriosis and a
      control abdominal surgery on the rat bladder.
AB  - OBJECTIVE: To determine, in rats, how surgically induced endometriosis and a
      control surgery (partial hysterectomy; sutures in abdomen) affects micturition
      thresholds and bladder vascular permeability. DESIGN: Two animal studies, each
      performed in three groups of urethane-anesthetized rats in proestrus. SETTING:
      Academic facility. ANIMAL(S): Seventy-three female, regularly cycling Sprague
      Dawley rats studied in proestrus. INTERVENTION(S): Surgical induction of
      endometriosis (ENDO), surgical control (shamENDO), intact control (NoSURG), and
      bladder inflammation via intravesicular turpentine in all three groups. MAIN
      OUTCOME MEASURE(S): [1] Micturition thresholds (MTs; volume voiding thresholds),
      as measured by repetitive transurethral cystometry before and after bladder
      inflammation and [2] bladder inflammation, as assessed by extravasation of Evans
      Blue dye. RESULT(S): In the uninflamed bladder, MTs were significantly lower and
      dye extravasation significantly higher in ENDO rats than in shamENDO and NoSURG
      rats. Bladder inflammation increased dye extravasation in all groups and reduced
      MTs in the NoSURG and ENDO rats, but not in the shamENDO rats. CONCLUSION(S):
      Endometriosis reduces MTs and produces signs of inflammation in the healthy
      bladder. Surprisingly, the control surgical procedure (partial hysterectomy;
      sutures on mesenteric blood vessels) protects bladder reflexes from the influence
      of bladder inflammation, a condition that is named silent bladder inflammation.
      Such cross-system inducing and masking effects have important clinical relevance.

PMID- 16962121
TI  - A cDNA for European sea bass (Dicentrachus labrax) 11beta-hydroxylase: gene
      expression during the thermosensitive period and gonadogenesis.
AB  - Steroid P450 11beta-hydroxylase, encoded by the CYP11B gene, is a key
      mitochondrial enzyme for the production of 11-oxygenated androgens, which have
      been shown to be potent masculinising steroids in several fish species. In this
      study we have isolated a CYP11B cDNA of 1903 base pairs from the testis of
      European sea bass (Dicentrarchus labrax) encoding a predicted protein of 552
      amino acids. The amino acid identities to other vertebrate 11beta-hydroxylase
      proteins ranged from 66% to 72% to other fish; 45% to amphibian and 35-39% to
      mammalian. Southern blot indicated that a single CYP11B gene is present. Northern
      blot analysis detected two transcripts in testis and head kidney, one of the same
      size of the isolated clone and the other of 3.9 kb. Reverse transcriptase
      polymerase chain reaction showed abundant mRNA expression only in testis and head
      kidney, being residual in a range of other tissues. Expression of CYP11B and
      CYP19A (which encodes for ovarian aromatase) was detected from at least 4 days
      post-hatching and did not appear to be affected by rearing temperature (15 and 20
      degrees C) during the first 60 days, a period in which high temperatures promote
      masculinisation in European sea bass. Throughout, gonadogenesis (60-300 dph), a
      highly dimorphic pattern of CYP11B expression was consistent with a role of this
      gene in testicular development.

PMID- 16962122
TI  - Internet communities for recruitment of cancer patients into an Internet survey:
      a discussion paper.
AB  - The purpose of this paper is to provide future directions for the usage of
      Internet communities (ICs) for recruitment of research participants based on
      issues raised in an Internet survey among 132 cancer patients. About 317 general
      and 233 ethnic-specific Internet Cancer Support Groups and 1588 ethnic-specific
      ICs were contacted to recruit cancer patients. Research staff recorded issues and
      wrote memos during the recruitment process. The written memos and records were
      later analyzed using content analysis. The issues included: (a) difficulty in
      identifying appropriate ICs and potential participants, (b) meta-tags, (c)
      dominant white and women groups, (d) dynamics inside ICs, (e) difficulty in trust
      building, and (f) potential selection bias. The findings suggest that researchers
      thoroughly review the ICs' information, be recognizant of potential gender and
      ethnic issues and current trends in Internet interaction, and consider potential
      selection bias.

PMID- 16962123
TI  - Job satisfaction and its related factors: a questionnaire survey of hospital
      nurses in Mainland China.
AB  - BACKGROUND: The widespread nursing shortage is of concern in Mainland China and
      globally. Factors underpinning the increased mobility of the nursing workforce
      and their contribution to nurses' turnover thus merit attention. Understanding
      nurses' job satisfaction is important, as this is a key factor in nurses'
      turnover. OBJECTIVE: The study aimed to explore nurses' views and experience
      regarding different components of their working lives in Mainland China. METHODS:
      A cross-sectional survey design was selected and 512 nurses working in the
      medical and surgical departments in two teaching hospitals in Beijing completed
      questionnaires yielding a response rate of 81%. RESULTS: More than half of nurses
      (53.7%; n=275) were satisfied or very satisfied with their jobs and 15% (n=77)
      felt moderate to extreme occupational stress. The majority of the sample reported
      a high level of organizational commitment (63.7%; n=326) and professional
      commitment (85.9%; n=440) and only 5.9% (n=30) and 10.0% (n=51), respectively
      reported role conflict and role ambiguity often or very often. Nurses with a
      diploma or associate degree reported greater professional commitment and a lower
      level of role conflict than those with a bachelor degree (p<0.05), but there were
      no significant differences in job satisfaction, organizational commitment,
      occupational stress and role ambiguity by educational programme (p>0.05).
      CONCLUSIONS: Hospital nurses' positive feelings regarding their working lives may
      be influenced by developments in the health care system and the nursing
      profession in Mainland China. Nurses' educational level is an influencing factor
      on nurses' views and experiences of their working lives with the findings
      suggesting the need to develop a clinical career ladder for nursing staff in
      Mainland China.

PMID- 16962124
TI  - Pretreatments of chromatographic fingerprints for quality control of herbal
      medicines.
AB  - Pretreatments of chromatographic fingerprints are important for quality control
      of herbal medicines and they include data correction and data transformation. The
      data correction can reduce the variations of experimental procedures, and data
      transformation can put different weights on the different parts of the
      fingerprints. In this paper, a new target peak alignment (TPA) procedure has been
      proposed to correct the retention time shifts, multiplicative scattering
      correction (MSC) has been introduced for response correction. Then the similarity
      of the fingerprints with mean and median fingerprints is used to evaluate the
      quality of herbal medicines (HMs). Furthermore, different data transformation
      methods with kernel principal component analysis (PCA) have been applied to the
      data and their effects were discussed. The proposed approaches have been
      demonstrated by the essential oils data set of a herbal medicine, named
      Houttuynia cordata (HC), containing samples from different geographic origins.
      The experimental results indicate that the proposed approaches may be helpful in
      the quality control of herbal medicines by fingerprints.

PMID- 16962125
TI  - Analysis of xanthohumol and isoxanthohumol in different hop products by liquid
      chromatography-diode array detection-electrospray ionization tandem mass
      spectrometry.
AB  - An analytical methodology based on the sample extraction with methanol/formic
      acid by ultra-sonication and subsequent analysis by high-performance liquid
      chromatography with diode array detection is proposed for the determination of
      xanthohumol (XN) and isoxanthohumol (IXN) in different hop products. The identity
      of the compounds was confirmed by high-performance liquid
      chromatography/electrospray ionization tandem mass spectrometry in positive ion
      mode. The performance of the method was assessed by the evaluation of parameters
      such as absolute recovery, repeatability, linearity and limits of detection and
      quantitation. This methodology was applied to investigate the impact of the
      extraction process of the hop products on the amount of xanthohumol and
      isoxanthohumol. The ethanolic extract revealed to be the hop product richest in
      xanthohumol (3.75+/-0.05 g/100 g) relatively to the pellets (0.62+/-0.01 g/100 g)
      and supercritical CO2 extract (0.089+/-0.001 g/100 g).

PMID- 16962126
TI  - A comparison of liquid chromatography, capillary electrophoresis, and mass
      spectrometry methods to determine xyloglucan structures in black currants.
AB  - Different separation (HPAEC, RP-HPLC, CE) and identification (MALDI-TOF-MS, ESI
      MS(n)) techniques were compared to analyse oligosaccharides obtained after
      incubation of xyloglucan with endo-glucanase. It was possible to analyse
      xyloglucan oligosaccharides with each technique. Several techniques, including
      off line (HPAEC-MALDI-TOF-MS) or online (CE-ESI-MS(n), RP-HPLC-ESI-MS(n))
      connection provided complementary information on xyloglucan structure. Online CE
      MS and RP-HPLC-MS are described for the first time in xyloglucan analysis.
      Advantages and disadvantages of the techniques for different purposes such as
      structural characterisation of oligosaccharides or oligosaccharide profiling are
      discussed. Black currant xyloglucans had a rather simple XXXG-type structure with
      galactose and fucose containing side chains.

PMID- 16962127
TI  - Epinephrine QT stress testing in congenital long QT syndrome.
AB  - Epinephrine QT stress testing is an effective diagnostic tool to unmask concealed
      Long QT Syndrome (LQTS), particularly type 1 LQTS (LQT1). Unique responses have
      also been observed in patients with LQT2 and LQT3, making this test invaluable in
      the diagnostic work-up of LQTS. This article reviews the epinephrine QT stress
      test, explains the pathological basis of differential responses among patients
      and healthy individuals, and describes the methodology for conducting the test
      and the interpretation of the responses. We have also attempted to highlight the
      differences between the two major LQTS epinephrine QT stress test protocols, the
      Mayo protocol and the Shimizu protocol.

PMID- 16962128
TI  - Electrocardiogram dynamics for risk stratification in ST-segment elevation
      myocardial infarction--immediate and serially updated information on outcome.
AB  - Early and serially updated predictions of final infarct-size and clinical outcome
      -before, during and after reperfusion treatment of ST-elevation myocardial
      infarction might allow a more individualized treatment: High-risk patients with a
      predicted major loss of viable myocardium can be identified immediately or during
      therapy, at a stage when treatment may still be modified; and low-risk patients
      with predictions of small infarcts and good outcome already after standard
      primary reperfusion therapy can be identified and thereby avoid a possibly
      harmful intensified treatment. The necessary information for such predictions
      seem to be available from the standard 12-lead ECG and from ST-segment
      monitoring. Today this information, however, is not readily available in clinical
      practice. Automated algorithms need to be engineered for a broader use and for
      possibilities of a refined triage and thus for a more individualized strategy of
      reperfusion therapy.

PMID- 16962130
TI  - Potassium channel remodeling in cardiac hypertrophy.
AB  - Cardiac hypertrophy is an adaptive process against increased work loads; however,
      hypertrophy also presents substrates for lethal ventricular arrhythmias,
      resulting in sudden arrhythmic deaths that account for about one third of deaths
      in cardiac hypertrophy. To maintain physiological cardiac function in the face of
      increased work loads, hypertrophied cardiomyocytes undergo K(+) channel
      remodeling that provides a prolongation in action potential duration and an
      increase in Ca(2+) entry. Increased Ca(2+) entry, in turn, activates signaling
      mechanisms including a calcineruin/NFAT pathway to permit remodeling of the K(+)
      channels. This results in a positive feedback loop between the K(+) channel
      remodeling and altered Ca(2+) handling; this loop may represent a potential
      therapeutic target against sudden arrhythmic deaths in cardiac hypertrophy. The
      purposes of this review are to: (1) discuss types of K(+) channels and their mRNA
      that undergo remodeling in cardiac hypertrophy; (2) report on recent research on
      molecular mechanisms of K(+) channel remodeling; and (3) address physiological
      events underlying new therapeutic modalities to ameliorate arrhythmias and sudden
      death in cardiac hypertrophy.

PMID- 16962131
TI  - K+ transport and energetics in Kir6.2(-/-) mouse hearts assessed by 87Rb and 31P
      magnetic resonance and optical spectroscopy.
AB  - Cardiac sarcolemmal K(ATP) channels are crucial in adaptation to stress caused by
      metabolic inhibition and moderate exercise, which requires not only down
      regulation of energy spending, but also up-regulation of mitochondrial ATP
      synthesis. To investigate sarcolemmal and mitochondrial effects of a Kir6.2 (K(+)
      ion-selective subunit of the channel) knockout, we used non-invasive techniques
      ((87)Rb, (31)P NMR and optical spectroscopy) to study (1) K(+) fluxes, (2) high
      energy phosphates, (3) the cytochrome c oxidase redox state, (4) myoglobin
      deoxygenation, and (5) contractile function at the baseline and in response to
      metabolic uncoupling with 2,4-dintrophenol (DNP) and stimulation with
      isoproterenol in Langendorff-perfused mouse hearts. Comparison with control
      C57BL6 hearts demonstrated that the Kir6.2 knockout resulted in: (a) a lack of
      stimulation of the unidirectional potassium efflux from the hearts when K(ATP)
      channels were activated metabolically by DNP (50 muM, 20 min); (b) a decrease in
      ATP, but not phosphocreatine, at the baseline, that became even more pronounced
      when the hearts were subjected to stress due to metabolic inhibition or increased
      workload caused by isoproterenol infusion (0.1 microM, 20 min); (c) significantly
      higher reduction of cytochrome c oxidase in response to DNP uncoupling; (d) a
      blunted response to isoproterenol stimulation. Thus Kir6.2 knockout is associated
      with decreased tolerance of mouse hearts to metabolic inhibition and
      catecholamine stress.

PMID- 16962132
TI  - Changes in nucleoporin domain topology in response to chemical effectors.
AB  - Nucleoporins represent the molecular building blocks of nuclear pore complexes
      (NPCs), which mediate facilitated macromolecular trafficking between the
      cytoplasm and nucleus of eukaryotic cells. Phenylalanine-glycine (FG) repeat
      motifs are found in about one-third of the nucleoporins, and they provide major
      binding or docking sites for soluble transport receptors. We have shown recently
      that localization of the FG-repeat domains of vertebrate nucleoporins Nup153 and
      Nup214 within the NPC is influenced by its transport state. To test whether
      chemical effectors, such as calcium and ATP, influence the localization of the FG
      repeat domains of Nup153 and Nup214 within the NPC, we performed immuno-electron
      microscopy of Xenopus oocyte nuclei using domain-specific antibodies against
      Nup153 and Nup214, respectively. Ca2+ and ATP are known to induce conformational
      changes in the NPC architecture, especially at the cytoplasmic face, but also at
      the nuclear basket of the NPC. We have found concentrations of calcium in the
      micromolar range or 1 mM ATP in the surrounding buffer leaves the spatial
      distribution of the FG-repeat of Nup153 and Nup214 largely unchanged. In
      contrast, ATP depletion, calcium store depletion by EGTA or thapsigargin, and
      high concentrations of divalent cation (i.e. 2 mM Ca2+ and 2 mM Mg2+) constrain
      the distribution of the FG-repeats of Nup153 and Nup214. Our data suggest that
      the location of the FG-repeat domains of Nup153 and Nup214 is sensitive to
      chemical changes within the near-field environment of the NPC.

PMID- 16962133
TI  - Characterization of the reactivity determinants of a novel hairpin substrate of
      yeast RNase III.
AB  - RNase III enzymes form a conserved family of proteins that specifically cleave
      double-stranded (dsRNA). These proteins are involved in a variety of cellular
      functions, including the processing of many non-coding RNAs, mRNA decay, and RNA
      interference. Yeast RNase III (Rnt1p) selects its substrate by recognizing the
      structure generated by a conserved NGNN tetraloop (G2-loop). Mutations of the
      invariant guanosine stringently inhibit binding and cleavage of all known Rnt1p
      substrates. Surprisingly, we have found that the 5' end of small nucleolar RNA 48
      is processed by Rnt1p in the absence of a G2-loop. Instead, biochemical and
      structural analyses revealed that cleavage, in this case, is directed by a
      hairpin capped with an AAGU tetraloop, with a preferred adenosine in the first
      position (A1-loop). Chemical probing indicated that A1-loops adopt a distinct
      structure that varies at the 3' end where Rnt1p interacts with G2-loops.
      Consistently, chemical footprinting and chemical interference assays indicate
      that Rnt1p binds to G2 and A1-loops using different sets of nucleotides. Also,
      cleavage and binding assays showed that the N-terminal domain of Rnt1p aids
      selection of A1-capped hairpins. Together, the results suggest that Rnt1p
      recognizes at least two distinct classes of tetraloops using flexible protein RNA
      interactions. This underscores the capacity of double-stranded RNA binding
      proteins to use several recognition motifs for substrate identification.

PMID- 16962135
TI  - T cell receptor recognition via cooperative conformational plasticity.
AB  - Although T cell receptor cross-reactivity is a fundamental property of the immune
      system and is implicated in numerous autoimmune pathologies, the molecular
      mechanisms by which T cell receptors can recognize and respond to diverse ligands
      are incompletely understood. In the current study we examined the response of the
      human T cell lymphotropic virus-1 (HTLV-1) Tax-specific T cell receptor (TCR) A6
      to a panel of structurally distinct haptens coupled to the Tax 11-19 peptide with
      a lysine substitution at position 5 (Tax5K, LLFG[K-hapten]PVYV). The A6 TCR could
      cross-reactively recognize one of these haptenated peptides, Tax-5K-4-(3-Indolyl)
      butyric acid (IBA), presented by HLA-A*0201. The crystal structures of Tax5K
      IBA/HLA-A2 free and in complex with A6 reveal that binding is mediated by a
      mechanism of cooperative conformational plasticity involving conformational
      changes on both sides of the protein-protein interface, including the TCR
      complementarity determining region (CDR) loops, Valpha/Vbeta domain orientation,
      and the hapten-modified peptide. Our findings illustrate the complex role that
      protein dynamics can play in TCR cross-reactivity and highlight that T cell
      receptor recognition of ligand can be achieved through diverse and complex
      molecular mechanisms that can occur simultaneously in the interface, not limited
      to molecular mimicry and CDR loop shifts.

PMID- 16962134
TI  - Sites of interaction of a precursor polypeptide on the export chaperone SecB
      mapped by site-directed spin labeling.
AB  - Export of protein into the periplasm of Escherichia coli via the general
      secretory system requires that the transported polypeptides be devoid of stably
      folded tertiary structure. Capture of the precursor polypeptides before they fold
      is achieved by the promiscuous binding to the chaperone SecB. SecB delivers its
      ligand to export sites through its specific binding to SecA, a peripheral
      component of the membrane translocon. At the translocon the ligand is passed from
      SecB to SecA and subsequently through the SecYEG channel. We have previously used
      site-directed spin labeling and electron paramagnetic resonance spectroscopy to
      establish a docking model between SecB and SecA. Here we report use of the same
      strategy to map the pathway of a physiologic ligand, the unfolded form of
      precursor galactose-binding protein, on SecB. Our set of SecB variants each
      containing a single cysteine, which was used in the previous study, has been
      expanded to 48 residues, which cover 49% of the surface of SecB. The residues on
      SecB involved in contacts were identified as those that, upon addition of the
      unfolded polypeptide ligand, showed changes in spectral line shape consistent
      with restricted motion of the nitroxide. We conclude that the bound precursor
      makes contact with a large portion of the surface of the small chaperone. The
      sites on SecB that interact with the ligand are compared with the previously
      identified sites that interact with SecA and a model for transfer of the ligand
      is discussed.

PMID- 16962136
TI  - Ultra-high resolution crystal structure of HIV-1 protease mutant reveals two
      binding sites for clinical inhibitor TMC114.
AB  - TMC114 (darunavir) is a promising clinical inhibitor of HIV-1 protease (PR) for
      treatment of drug resistant HIV/AIDS. We report the ultra-high 0.84 A resolution
      crystal structure of the TMC114 complex with PR containing the drug-resistant
      mutation V32I (PR(V32I)), and the 1.22 A resolution structure of a complex with
      PR(M46L). These structures show TMC114 bound at two distinct sites, one in the
      active-site cavity and the second on the surface of one of the flexible flaps in
      the PR dimer. Remarkably, TMC114 binds at these two sites simultaneously in two
      diastereomers related by inversion of the sulfonamide nitrogen. Moreover, the
      flap site is shaped to accommodate the diastereomer with the S-enantiomeric
      nitrogen rather than the one with the R-enantiomeric nitrogen. The existence of
      the second binding site and two diastereomers suggest a mechanism for the high
      effectiveness of TMC114 on drug-resistant HIV and the potential design of new
      inhibitors.

PMID- 16962137
TI  - Mechanistic studies of mini-TAR RNA/DNA annealing in the absence and presence of
      HIV-1 nucleocapsid protein.
AB  - HIV-1 reverse transcription involves several nucleic acid rearrangements, which
      are catalyzed by the nucleocapsid protein (NC). Annealing of the trans-activation
      response element (TAR) DNA hairpin to a complementary TAR RNA hairpin, resulting
      in the formation of an extended 98-base-pair duplex, is an essential step in the
      minus-strand transfer step of reverse transcription. To elucidate the TAR RNA/DNA
      annealing reaction pathway, annealing kinetics were studied systematically by gel
      shift assays performed in the presence or absence of HIV-1 NC. Truncated 27
      nucleotide mini-TAR RNA and DNA constructs were used in this work. In the absence
      of NC, the annealing is slow, and involves the fast formation of an unstable
      extended "kissing" loop intermediate, followed by a slower strand exchange
      between the terminal stems. This annealing is very sensitive to loop-loop
      complementarity, as well as to nucleic acid concentration, ionic strength and
      temperature. NC stimulates the annealing approximately 5000-fold by stabilizing
      the bimolecular intermediate approximately 100 to 200-fold, and promoting the
      subsequent strand exchange reaction approximately 10 to 20-fold. NC concentration
      dependence studies suggest that there is a direct correlation between the amount
      of NC required to stabilize the intermediate and the amount needed to induce mini
      TAR aggregation. Whereas saturating levels of NC are required to efficiently
      aggregate nucleic acids, sub-saturating NC is sufficient to significantly enhance
      duplex destabilization. Equilibrium levels of mini-TAR RNA/DNA annealing were
      also measured under a variety of conditions. Taken together, the results
      presented here provide a quantitative accounting of HIV-1 NC's aggregation and
      duplex destabilizing activity, and provide insights into the universal nucleic
      acid chaperone activity of this essential viral protein.

PMID- 16962138
TI  - Methyl substituents at the 11 or 12 position of retinal profoundly and
      differentially affect photochemistry and signalling activity of rhodopsin.
AB  - The C-11=C-12 double bond of the retinylidene chromophore of rhodopsin holds a
      central position in its light-induced photoisomerization and hence the
      photosensory function of this visual pigment. To probe the local environment of
      the HC-11=C-12H element we have prepared the 11-methyl and 12-methyl derivatives
      of 11-Z retinal and incorporated these into opsin to generate the rhodopsin
      analogs 11-methyl and 12-methyl rhodopsin. These analog pigments form with much
      slower kinetics and lower efficiency than the native pigment. The initial
      photochemistry and the signaling activity of the analog pigments were
      investigated by UV-vis and FTIR spectroscopy, and by a G protein activation
      assay. Our data indicate that the ultrafast formation of the first
      photointermediate is strongly perturbed by the presence of an 11-methyl
      substituent, but much less by a 12-methyl substituent. These results support the
      current concept of the mechanism of the primary photoisomerization event in
      rhodopsin. An important stronghold of this concept is an out-of-plane movement of
      the C-12H element, which is facilitated by torsion as well as extended positive
      charge delocalization into the C-10-C-13 segment of the chromophore. We argue
      that this mechanism is maintained principally with a methyl substituent at C-12.
      In addition, we show that both an 11-methyl and a 12-methyl substitutent perturb
      the photointermediate cascade and finally yield a low-activity state of the
      receptor. The 11-methyl pigment retains about 30% of the G protein activation
      rate of native rhodopsin, while the 12-methyl chromophore behaves like an inverse
      agonist up to at least 20 degrees C, trapping the protein in a perturbed Meta-I
      like conformation. We conclude that the isomerization region of the chromophore
      and the spatial structure of the binding site are finely tuned, in order to
      achieve a high photosensory potential with an efficient pathway to a high
      activity state.

PMID- 16962139
TI  - Multisite promiscuity in the processing of endogenous substrates by human
      carboxylesterase 1.
AB  - Human carboxylesterase 1 (hCE1) is a drug and endobiotic-processing serine
      hydrolase that exhibits relatively broad substrate specificity. It has been
      implicated in a variety of endogenous cholesterol metabolism pathways including
      the following apparently disparate reactions: cholesterol ester hydrolysis (CEH),
      fatty acyl Coenzyme A hydrolysis (FACoAH), acyl-Coenzyme A:cholesterol
      acyltransfer (ACAT), and fatty acyl ethyl ester synthesis (FAEES). The structural
      basis for the ability of hCE1 to perform these catalytic actions involving large
      substrates and products has remained unclear. Here we present four crystal
      structures of the hCE1 glycoprotein in complexes with the following endogenous
      substrates or substrate analogues: Coenzyme A, the fatty acid palmitate, and the
      bile acids cholate and taurocholate. While the active site of hCE1 was known to
      be promiscuous and capable of interacting with a variety of chemically distinct
      ligands, these structures reveal that the enzyme contains two additional ligand
      binding sites and that each site also exhibits relatively non-specific ligand
      binding properties. Using this multisite promiscuity, hCE1 appears structurally
      capable of assembling several catalytic events depending, apparently, on the
      physiological state of the cellular environment. These results expand our
      understanding of enzyme promiscuity and indicate that, in the case of hCE1,
      multiple non-specific sites are employed to perform distinct catalytic actions.

PMID- 16962141
TI  - Whole-cell modeling framework in which biochemical dynamics impact aspects of
      cellular geometry.
AB  - A mathematical framework for modeling biological cells from a physicochemical
      perspective is described. Cells modeled within this framework consist of at least
      two regions, including a cytosolic volume encapsulated by a membrane surface. The
      cytosol is viewed as a well-stirred chemical reactor capable of changing volume
      while the membrane is assumed to be an oriented 2-D surface capable of changing
      surface area. Two physical properties of the cell, namely volume and surface
      area, are determined by (and determine) the reaction dynamics generated from a
      set of chemical reactions designed to be occurring in the cell. This framework
      allows the modeling of complex cellular behaviors, including self-replication.
      This capability is illustrated by constructing two self-replicating prototypical
      whole-cell models. One protocell was designed to be of minimal complexity; the
      other to incorporate a previously reported well-known mechanism of the eukaryotic
      cell cycle. In both cases, self-replicative behavior was achieved by seeking
      stable physically possible oscillations in concentrations and surface-to-volume
      ratio, and by synchronizing the period of such oscillations to the doubling of
      cytosolic volume and membrane surface area. Rather than being enforced externally
      or artificially, growth and division occur naturally as a consequence of the
      assumed chemical mechanism operating within the framework.

PMID- 16962140
TI  - Sarin experiences in Japan: acute toxicity and long-term effects.
AB  - Two terrorist attacks with the nerve agent Sarin affected citizens in Matsumoto
      and Tokyo, Japan in 1994 and 1995, killing 19 and injuring more the 6000. Sarin,
      a very potent organophosphate nerve agent, inhibits acetylcholinesterase (AchE)
      activity within the central, peripheral, and autonomic nervous systems. Acute and
      long-term Sarin effects upon humans were well documented in these two events.
      Sarin gas inhalation caused instantaneous death by respiratory arrest in 4
      victims in Matsumoto. In Tokyo, two died in station yards and another ten victims
      died in hospitals within a few hours to 3 months after poisoning. Six victims
      with serum ChE below 20% of the lowest normal were resuscitated from
      cardiopulmonary arrest (CPA) or coma with generalized convulsion. Five recovered
      completely and one remained in vegetative state due to anoxic brain damage. EEG
      abnormalities persisted for up to 5 years. Miosis and copious secretions from the
      respiratory and GI tracts (muscarinic effects) were common in severely to
      slightly affected victims. Weakness and twitches of muscles (nicotinic effects)
      appeared in severely affected victims. Neuropathy and ataxia were observed in
      small number (less than 10%) of victims, which findings disappeared between 3
      days and 3 months. Leukocytosis and high serum CK levels were common.
      Hyperglycemia, ketonuria, low serum triglyceride, hypopotassemia were observed in
      severely affected victims, which abnormalities were attributed to damage of the
      adrenal medulla. Oximes, atropine sulphate, diazepam and ample intravenous
      infusion were effective treatments. Pralidoxime iodide IV reversed cholinesterase
      and symptoms quickly even if administered 6 h after exposure. Post Traumatic
      Stress Disorder (PTSD) was less than 8% after 5 years. However, psychological
      symptoms continue in victims of both incidents. In summary, both potent toxicity
      and quick recovery from critical ill conditions were prominent features.
      Conventional therapies proved effective in Sarin incidents in Japan.

PMID- 16962142
TI  - Methotrexate induces seizure and decreases glutamate uptake in brain slices:
      prevention by ionotropic glutamate receptors antagonists and adenosine.
AB  - Methotrexate (MTX)-induced neurotoxicity may occur after intrathecal or systemic
      administration at low, intermediate and high doses for the treatment of malignant
      or inflammatory diseases. The mechanisms of MTX neurotoxicity are not totally
      understood, and appear to be multifactorial. In this study we characterized a
      model of MTX-induced seizures in mice to evaluate the convulsive and toxic MTX
      properties. Additionally, the effect of MTX-induced seizures on the activity of
      glutamate transporters, as well as the anticonvulsant role of MK-801, DNQX and
      adenosine on glutamate uptake in brain slices was investigated . MTX induced
      tonic-clonic seizures in approximately 95% of animals and pre-treatment with MK
      801, DNQX and adenosine prevented seizure in 80%, 62% and 50% of animals,
      respectively. Moreover, MTX leads 59% of mice to death, which was prevented in
      100% and 94% when animals received MK-801 and DNQX, respectively. Glutamate
      uptake decreased by 20% to 30% in cortical slices after MTX-induced seizures.
      Interestingly, when seizures were prevented by MK-801, DNQX or adenosine,
      glutamate uptake activity remained at the same level as the control group. Thus,
      our results demonstrate the involvement of the glutamatergic system in MTX
      induced seizures.

PMID- 16962143
TI  - Effect of anti-TNFalpha treatment on circulating endothelial progenitor cells
      (EPCs) in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity
      and mortality, which may be attenuated by anti-inflammatory treatment.
      Endothelial progenitor cells (EPCs) have the ability to differentiate into mature
      endothelium and have a potentially reparative role protecting against ischemia
      and atherosclerosis. OBJECTIVE: To investigate the effect of treatment with
      infliximab on the number and functional capacity of endothelial progenitor cells
      (EPCs) in patients with RA, as a possible mechanism for reducing cardiovascular
      morbidity in this disorder. METHODS:  PATIENTS: Active seropositive RA patients
      (N = 14) considered candidates for starting infliximab treatment, were recruited.
      Assessment, based on DAS-28, was performed before treatment and 14 days later.
      Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by the
      colony-forming unit (CFU) method. Endothelial phenotyping of CFU was performed by
      immunofluorescence employing antibodies to Tie-2 VEGF-receptor 2, and CD31. EPC
      Functional properties were evaluated by fibronectin adherance. RESULTS: A
      significant 33.4% increase (p < 0.001) in EPC levels was observed after
      infliximab. A 60% increase was noted in the EPC differentiation scale, (p <
      0.002) while a 37.6% increase was observed in mean EPC adhesion (p < 0.001).
      These changes were associated with a 17.5% decrease in the DAS-28 (p < 0.0001). A
      significant correlation was observed between the clinical response, reflected by
      changes in DAS-28 and the degree of increase in EPC CFUs. CONCLUSION: A single
      dose of infliximab improved the number and functional properties of EPCs, in
      parallel with an early clinical effect, suggesting a possible mechanism by which
      anti-inflammatory treatment may reduce cardiovascular risk in RA patients.

PMID- 16962144
TI  - Relationship among nitric oxide, leptin, ACTH, corticosterone, and IL-1beta, in
      the early and late phases of adjuvant arthritis in male Long Evans rats.
AB  - Leptin, a hormone regulating body weight, food intake, and metabolism, is
      associated with activation of immune cells and inflammation. In this study we
      analyzed levels of leptin, adrenocorticotropic hormone (ACTH), corticosterone,
      interleukin 1beta (IL-1beta), and nitric oxide (NO) production on days 10 and 22
      of adjuvant arthritis (AA) in male Long Evans rats to ascertain possible
      relationship of leptin with its modulators during the early and late phases of
      chronic inflammation. The circulating leptin levels were significantly reduced
      already on day 10 of AA compared to controls (1.97+/-0.22 ng/ml vs. 3.08+/-0.25
      ng/ml, p<0.05); on day 22 no significant further drop was observed (1.06+/-0.21
      ng/ml). Leptin mRNA in epididymal fat tissue was reduced in arthritic animals
      compared to controls on day 22 (0.61+/-0.09 vs. 1.30+/-0.1 arbU/GAPDH (p<0.01).
      IL-1beta concentration in spleen was enhanced on day 10 of AA (24.55+/-4.67
      pg/100 microg protein vs. 14.33+/-1.71 pg/100 microg protein; p<0.05); on day 22
      it did not differ from controls. ACTH and corticosterone levels were
      significantly elevated only on day 22 of AA (ACTH: 306.17+/-42.22 pg/ml vs.
      157.61+/-23.94 pg/ml; p<0.05; corticosterone: 5.24+/-1.38 microg/100 ml vs.
      1.05+/-0.23 microg/100 ml; p<0.01). Nitrate levels were enhanced similarly on
      days 10 (49.86+/-1.83 microM) and 22 of AA (43.58+/-2.17 microM), compared to
      controls (23.42+/-1.39 microM, p<0.001). These results show that corticosterone
      does not stimulate leptin production during AA. The suppression of leptin may be
      a consequence of permanent activation of NO, IL-1beta, and of lower weight gain.
      Circulating leptin does not seem to play a key role in the progression of chronic
      arthritis.

PMID- 16962145
TI  - Continued post-bleaching decline and changed benthic community of a Kenyan coral
      reef.
AB  - During the global coral bleaching event of 1997/1998 Kenyan reefs experienced
      between 50% and 90% coral mortality, with coral cover at Malindi being reduced
      from 35-45% (pre-bleaching) to 10-20%. Even before this event there was concern
      that these reefs were being impacted by increased sediment loads from the nearby
      Sabaki River. Here we report that since 1998 coral cover has declined yet further
      with, in 2004, means of 5.1% being recorded at North Reef (within the non-fished
      Malindi Marine National Park) and 2.3% on Leopard Reef (within the fished Marine
      Reserve). Prior to bleaching 55 coral genera were recorded from the area,
      currently we find only 23. Meanwhile algal cover, especially the calcareous green
      alga Halimeda, has increased, and on Leopard Reef is twice that on North Reef.
      Taken with the evidence of previous studies, these data suggest a combined impact
      of coral bleaching with sedimentation and fishing.

PMID- 16962146
TI  - The psychological, neurochemical and functional neuroanatomical mediators of the
      effects of positive and negative mood on executive functions.
AB  - In this review we evaluate the cognitive and neural effects of positive and
      negative mood on executive function. Mild manipulations of negative mood appear
      to have little effect on cognitive control processes, whereas positive mood
      impairs aspects of updating, planning and switching. These cognitive effects may
      be linked to neurochemistry: with positive mood effects mediated by dopamine
      while negative mood effects may be mediated by serotonin levels. Current evidence
      on the effects of mood on regional brain activity during executive functions,
      indicates that the prefrontal cortex is a recurrent site of integration between
      mood and cognition. We conclude that there is a disparity between the importance
      of this topic and awareness of how mood affects, executive functions in the
      brain. Most behavioural and neuroimaging studies of executive function in normal
      samples do not explore the potential role of variations in mood, yet the evidence
      we outline indicates that even mild fluctuations in mood can have a significant
      influence on neural activation and cognition.

PMID- 16962147
TI  - Development of action representation during adolescence.
AB  - During adolescence the body undergoes many physical changes. These changes
      necessitate an updating of internal models of action. Here, we tested the
      hypothesis that internal models undergo refinement between adolescence and
      adulthood. We investigated the chronometry of executed and imagined hand actions,
      which relies on internal models, in 40 adolescents (24 males; mean age 13.1
      years) and 33 adults (15 males; mean age 27.5 years). In two different motor
      imagery tasks, the time it took each participant to execute a hand movement was
      compared with the time it took them to imagine making that movement. For all
      participants, movement execution time significantly correlated with movement
      imagery time. However, there was a significant increase in the execution-imagery
      time correlation between adolescence and adulthood. Cognitive-motor efficiency
      per se did not change as indexed by both similar execution and imagery times on
      both tasks for the adolescents and adults. That it was only the correlation
      between imagined and executed actions that changed with age suggests that the
      developmental change was specific to generating accurate motor images and not a
      result of general cognitive improvement with age. The results support the notion
      that aspects of internal models are refined during adolescence. We suggest that
      this refinement may be facilitated by the development of parietal cortex during
      adolescence.

PMID- 16962148
TI  - Stress cardiovascular/autonomic interactions in mice.
AB  - Studies evaluated the role of the autonomic nervous system in the cardiovascular
      response to stress using radiotelemetric blood pressure (BP) recording coupled
      with autoregressive spectral analysis. Conscious male C57/BL6 mice with carotid
      arterial telemetric catheters were exposed to acute episodes of shaker stress
      before and after administration of cholinergic, beta1-adrenergic and alpha1
      adrenergic receptor antagonists. Pulse interval (PI) and systolic arterial
      pressure (SAP) were analyzed for variance and the low frequency (LF: 0.1-1.0 Hz)
      and high frequency (HF: 1-5 Hz) spectral components. Stress (5 min) increased BP
      and heart rate (HR) as well as PI and SAP variability. PI variance increased from
      41+/-6 to 75+/-14 ms2 while SAP variance increased from 25+/-5 to 55+/-9 mm Hg2.
      Autonomic blockade had specific effects on stress-induced changes in PI and SAP
      and their respective variability. Atropine reduced the tachycardia and abolished
      the increase in PI variance and its LF component. Data documents that in mice the
      cholinergic system is fundamental for the maintenance of HR variability. Atropine
      had no effects on the BP responses, either the increase in SAP or the variance
      associated with stress. Atenolol blocked the increase in PI and SAP variability
      induced by stress. Prazosin reduced the tachycardia produced by stress and
      blocked the increase in PI (only LF) and SAP variability. Using quantitative
      spectral analysis of telemetrically collected BP data in mice along with
      pharmacological antagonism, we were able to accurately determine the role of
      autonomic input in the mediation of the stress response. Data verify the role of
      sympathetic/parasympathetic balance in stress-induced changes in HR, BP and
      indices of variance.

PMID- 16962149
TI  - Ophiobolin E and 8-epi-ophiobolin J produced by Drechslera gigantea, a potential
      mycoherbicide of weedy grasses.
AB  - Drechslera gigantea, a fungal pathogen isolated from large crabgrass (Digitaria
      sanguinalis) and proposed as a potential mycoherbicide of grass weeds, produces
      phytotoxic metabolites in liquid and solid cultures. Ophiobolin A and three minor
      ophiobolins i.e., 6-epi-ophiobolin A, 3-anhydro-6-epi-ophiobolin A and ophiobolin
      I were obtained from the liquid culture broths. Interestingly and unexpectedly,
      ophiobolins also appeared in cultures of this fungus and they were isolated
      together with the known ophiobolins B and J, and designed as ophiobolin E and 8
      epi-ophiobolin J. They were characterized using essentially spectroscopic
      methods. It is noteworthy that D. gigantea produces such a plethora of bioactive
      organic substances. Some structure-activity relationship results are also
      discussed in this report.

PMID- 16962150
TI  - Phosphoproteins analysis in plants: a proteomic approach.
AB  - The study of phosphoproteome on a global scale represents one of the challenges
      in the post-genomic era. Here, we propose an integrated procedure starting from
      the crude protein extract, that consists of sequential purification steps, and
      ending up in the identification of phosphorylation sites. This involves (i) an
      enrichment in phosphoproteins with a commercially available chromatography
      matrix, (ii) a 2-D gel analysis of the enriched fraction followed by the
      selective staining with the phosphospecific fluorescent dye Pro-Q Diamond, (iii)
      a phosphopeptide capture, from the tryptic lysate of 2-D spots, using IMAC micro
      columns. In the end, the identification of the phosphoproteins and their
      corresponding phosphorylation sites were achieved by MALDI-TOF-TOF spectrometry.
      The method was applied to contrasting samples prepared from cell suspension
      cultures of Arabidopsis thaliana and roots of Medicago truncatula. The results
      obtained, demonstrated the robustness of the combination of two enrichment
      stages, sequentially at the protein and at the peptide levels, to analyse
      phosphoproteins in plants.

PMID- 16962151
TI  - A novel system to study adenovirus tropism to normal and malignant colon tissues.
AB  - We describe here a new organ culture system for the evaluation of viral tropism
      to colon carcinomas and normal colon tissues. Organ cultures of mouse and human
      colon retained viability for several days and thus facilitated studies of viral
      tropism. Two adenoviral vectors (AD) were compared in the study: AD5, that
      utilizes the CAR receptor, demonstrated poor infectivity to both normal and
      carcinoma tissues, while a capsid-modified-AD, recognizing haparan-sulfate
      receptor, demonstrated efficient infectivity of both tissues.
      Immunohistochemistry analysis demonstrated different viral tropism; while AD5
      infected only the colon epithelia, the capsid-modified-adeno infected both the
      epithelia and mesothelial layers. To investigate other determinants in the tissue
      that influence viral tropism, human cancer tissues were pretreated with
      collagenase and infected with the AD viruses. Increased infectivity and altered
      tropism were noted in the treated tumor tissue. Taken together, this ex vivo
      system indicated that receptor utilization and extracellular-matrix components
      influence AD viral tropism in solid tissues.

PMID- 16962152
TI  - Lack of neutralizing antibody response to HIV-1 predisposes to superinfection.
AB  - Occurrences of HIV-1 superinfection offer a unique opportunity to investigate the
      correlates of immune protection. Here we describe the neutralizing antibody
      responses of a cohort of recently infected individuals who were screened for HIV
      superinfection. Three individuals identified with HIV superinfection had less
      cross-protective and autologous neutralizing antibody response than their non
      superinfected case-controls. Neutralizing antibody may be crucial in the
      protection against superinfection and may explain why superinfection has only
      been documented following recent infection or treatment interruption. These data
      have considerable implications for vaccine development.

PMID- 16962153
TI  - Mosquito La protein binds to the 3' untranslated region of the positive and
      negative polarity dengue virus RNAs and relocates to the cytoplasm of infected
      cells.
AB  - The untranslated regions (UTRs) of the positive and negative strand RNAs of
      several viruses are major binding sites for cellular and viral proteins. Human La
      autoantigen is one of the cellular proteins that interacts with various positive
      strand RNA viral genomes including that of dengue virus (DEN) within the 5'- and
      3'-UTRs of positive (+) and the 3'-UTR of negative strand (-) RNA, and with the
      nonstructural proteins NS3 and NS5, that form DEN replicase complex. Since DEN
      replicates in human and mosquito cells, some functional interactions have to be
      conserved in both hosts. In the present report, we demonstrate that mosquito La
      protein interacts with the 3'-UTRs of (+) and (-) polarity viral RNAs. The
      localization of La protein, examined by confocal microscopy, indicates that La
      protein is redistributed in DEN-infected cells. Furthermore, the presence of La
      protein in an in vitro replication system inhibited RNA synthesis in a dose
      dependent manner, suggesting that La protein plays an important role in dengue
      virus replicative cycle.

PMID- 16962155
TI  - Matrix protein of VSV New Jersey serotype containing methionine to arginine
      substitutions at positions 48 and 51 allows near-normal host cell gene
      expression.
AB  - The matrix (M) protein of vesicular stomatitis virus (VSV) plays significant
      roles in the replication of VSV through its involvement in the assembly of virus
      particles as well as by facilitating the evasion of innate host cell defense
      mechanisms. The presence of methionine at position 51 (M51) of the matrix (M)
      protein of the VSV Indiana serotype (VSV(Ind)) has been proven to be crucial for
      cell rounding and inhibition of host cell gene expression. The M protein of
      VSV(Ind) with the substitution of M51 with arginine (R:M51R) results in the loss
      of inhibitory effects on host cell gene expression. The VSV(Ind) expressing the
      M(M51R) protein became the attractive oncolytic virus which is safer and more
      tumor-specific because the normal cells can clear the mutant VSV(Ind) easily but
      tumor cells are susceptible to the virus because a variety of tumor cells lack
      innate antiviral activities. We have studied the role of the methionines at
      positions 48 and 51 of the M protein of the New Jersey serotype of VSV (VSV(NJ))
      in the induction of cytopathic effects (CPE) and host cell gene expression. We
      have generated human embryonic kidney 293 cell lines inducibly expressing M
      proteins with M to R mutations at positions 48 and 51, either separately or
      together as a double mutant, and examined expression of heat shock protein 70
      (HSP70) as an indicator of host cell gene expression. We have also generated
      recombinant VSV(NJ) encoding the mutant M proteins M(M48R) or M(M48R+M51R) for
      the first time and tested for the expression of HSP70 in infected cells. Our
      results demonstrated that the M51 of VSV(NJ) M proteins has a major role in cell
      rounding and in suppressing the host cell gene expression either when the M
      protein was expressed alone in inducible cell lines or when expressed together
      with other VSV proteins by the recombinant VSV(NJ). Amino acid residue M48 may
      also have some role in cell rounding and in the inhibitory effects of VSV(NJ) M,
      which was demonstrated by the fact that the cell line expressing the double
      substitution mutant M(M48R+M51R) exhibited the least cytopathic effects and the
      least inhibitory effect on host cell gene expression.

PMID- 16962154
TI  - Contributions of E1A to mouse adenovirus type 1 pathogenesis following intranasal
      inoculation.
AB  - We investigated the role of mouse adenovirus type 1 (MAV-1) early region 1A (E1A)
      protein in adenovirus respiratory infection. Intranasal (i.n.) inoculation of
      mice with wild type (wt) virus induced chemokine and cellular inflammatory
      responses in the lung. We observed similar responses in mice infected with an E1A
      null mutant virus at the same dose, although the magnitude of these responses was
      lower. Levels of viral hexon gene expression were lower in the lung following
      infection with E1A-null virus than with wt virus. When input doses were adjusted
      so that equivalent viral loads were present following infection with varying
      doses of wt and E1A-null virus, we observed equivalent chemokine upregulation in
      the lung. Dissemination to the brain occurred following i.n. inoculation with
      equal doses of wt or E1A-null virus, but viral gene expression and viral loads
      were lower and the magnitude of chemokine responses was lower in brains of E1A
      null virus-infected mice. CD4 and CD8 T cells and neutrophils were recruited to
      the brains of mice infected with either wt or E1A-null virus. Together, these
      data suggest that MAV-1 E1A makes important contributions to viral replication in
      the lung and the brain following i.n. inoculation. However, E1A is not essential
      for the induction of inflammatory responses in the lung or for viral
      dissemination out of the lung.

PMID- 16962156
TI  - Cue combination in a combined feature contrast detection and figure
      identification task.
AB  - Target figures defined by feature contrast in spatial frequency, orientation or
      both cues had to be detected in Gabor random fields and their shape had to be
      identified in a dual task paradigm. Performance improved with increasing feature
      contrast and was strongly correlated among both tasks. Subjects performed
      significantly better with combined cues than with single cues. The improvement
      due to cue summation was stronger than predicted by the assumption of independent
      feature specific mechanisms, and increased with the performance level achieved
      with single cues until it was limited by ceiling effects. Further, cue summation
      was also strongly correlated among tasks: when there was benefit due to the
      additional cue in feature contrast detection, there was also benefit in figure
      identification. For the same performance level achieved with single cues, cue
      summation was generally larger in figure identification than in feature contrast
      detection, indicating more benefit when processes of shape and surface formation
      are involved. Our results suggest that cue combination improves spatial form
      completion and figure-ground segregation in noisy environments, and therefore
      leads to more stable object vision.

PMID- 16962157
TI  - Laboratory column study for remediation of MTBE-contaminated groundwater using a
      biological two-layer permeable barrier.
AB  - In this study, an in situ biological two-layer permeable reactive barrier system
      consisting of an oxygen-releasing material layer followed by a biodegradation
      layer was designed to evaluate the remediation effectiveness of MTBE-contaminated
      groundwater. The first layer containing calcium peroxide (CaO(2)) and other
      inorganic salts is to provide oxygen and nutrients for the immobilized microbes
      in the second layer in order to keep them in aerobic condition and maintain their
      normal metabolism. Furthermore, inorganic salts such as potassium dihydrogen
      phosphate (KH(2)PO(4)) and ammonium sulphate ((NH(4))(2)SO(4)) can also decrease
      the high pH caused by the alkali salt degraded from CaO(2). The second layer
      using granular expanded perlite as microbial carrier is able to biodegrade MTBE
      entering the barrier system. Batch experiments were conducted to identify the
      appropriate components of oxygen-releasing materials and the optimum pH value for
      the biodegradation of MTBE. At pH=8.0, the biodegradation efficiency of MTBE is
      the maximum and approximately 48.9%. A laboratory-scale experiment using two
      continuous upflow stainless-steel columns was then performed to evaluate the
      feasibility of this designed system. The fist column was filled with oxygen
      releasing materials at certain ratio by weight. The second column was filled with
      expanded perlite granules immobilizing MTBE-degrading microbial consortium.
      Simulated MTBE-contaminated groundwater, in which dissolved oxygen (DO) content
      was 0mg/L, was pumped into this system at a flow rate of 500mL/d. Samples from
      the second column were analyzed for MTBE and its major degradation byproduct.
      Results showed that MTBE could be removed, and its metabolic intermediate, tert
      butyl alcohol (TBA), could also be further degraded in this passive system.

PMID- 16962159
TI  - Structure-activity analysis of base and enzyme-catalyzed 4-hydroxybenzoyl
      coenzyme A hydrolysis.
AB  - In this study, the second-order rate constant k2 of base-catalyzed hydrolysis and
      the values of kcat, Km and kcat/Km of wild-type Pseudomonas sp. CBS3 4
      hydroxybenzoyl coenzyme A (4-HBA-CoA) thioesterase-catalyzed hydrolysis of 4-HBA
      CoA and its para-substituted analogs were measured. For the base-catalyzed
      hydrolysis, the plot of logk2 vs the sigma value of the para-substituents was
      linear with a slope (rho) of 1.5. In the case of the enzyme-catalyzed hydrolysis,
      the kcat/Km values measured for the para-substituted analogs defined substrate
      specificity. Asp32 was shown to play a key role in substrate recognition, and in
      particular, in the discrimination between the targeted substrate and other
      cellular benzoyl-CoA thioesters.

PMID- 16962160
TI  - Identifying the morphological signatures of hybridization in primate and human
      evolution.
AB  - Recent studies point to contact and possible admixture among contemporaneous
      hominin species during the Plio-Pleistocene. However, detection of hybridization
      in fossils-and especially fossil hominins-is contentious, and it is hindered in
      large part by our lack of understanding about how morphological hybridity is
      manifested in the primate skeleton. Here, we report on a study of known-pedigree,
      purebred yellow and olive baboons (n = 112) and their hybrids (n = 57), derived
      from the baboon colony of the Southwest Foundation for Biomedical Research. The
      hybrids were analyzed in two different groups: (1) F1 = olive x yellow first
      generation hybrids; (2) B1 = olive x F1 backcross hybrids. Thirty-nine metric
      variables were tested for heterosis and dysgenesis. Nonmetric data were also
      collected from the crania. Results show that these primate hybrids are somewhat
      heterotic relative to their parental populations, are highly variable, and
      display novel phenotypes. These effects are most evident in the dentition and
      probably indicate the mixing of two separately coadapted genomes and the
      breakdown in the coordination of early development, despite the fact that these
      populations diverged fairly recently. Similar variation is also observed in
      museum samples drawn from natural hybrid zones. The results offer a strategy for
      detecting hybrid zones in the fossil record; implications for interpreting the
      hominin fossil record are discussed.

PMID- 16962161
TI  - Mass transfer of soil indoors by track-in on footwear.
AB  - Inadvertent soil ingestion, especially by young children, can be an important
      route of exposure for many environmental contaminants. The introduction of
      exterior soil into the interior environment is a significant element of the
      exposure pathway. The unintentional collection of outside soil on footwear
      followed by subsequent deposition indoors is a principal route of soil ingress.
      Here we have investigated likely rates of dry and wet soil deposition on indoor
      hard surface flooring as a result of mass transfer from soiled footwear. In this
      pilot study, testing involved both single track-in events (with deposition
      resulting from a single progression of transfer steps) and multiple tracking
      actions (with deposition and dispersion resulting from repeated transfer steps).
      Based on soil mass recovery from the floor surface it was found that any
      contamination introduced by one-time track-in events was of limited spatial
      extent. In contrast, under repeated tracking conditions, with multiple soil
      incursions, widespread floor surface contamination was possible. Soil mass
      recovery was accomplished by brushing, by vacuum cleaner removal and by wet
      wiping. All the clean-up methods operated imperfectly and failed to remove all
      initially deposited soil. The level of floor surface soiling that resulted from
      the track-in tests, and the incomplete clean-up strongly suggest that under
      unrestricted transfer conditions rapid accumulation and dispersal of soil on
      indoor flooring is likely.

PMID- 16962162
TI  - 239+240Pu concentration and isotope ratio (240Pu/239Pu) in aerosols during high
      dust (Yellow Sand) period, Korea.
AB  - Concentration and isotope ratio of Pu were analyzed for aerosols collected at
      Anmyeondo located in the western coast of Korea using multiple collector
      inductively coupled plasma mass spectrometer equipped with desolvated micro
      concentric nebulizer. Aerosols were collected from June 2001 to April 2002 using
      high volume air sampler. The samples consist of high dust samples (Yellow Sand),
      and also low dust samples; maximum Al concentration was 74.2 microg/m(3) and
      minimum was 0.17 microg/m(3). Pu was concentrated using 0.1 ml TEVA resin columns
      after conc. HNO(3) extraction. Isotope dilution using (242)Pu spike and mass bias
      correction using (233)U and (236)U mixed solution enabled the quantification of
      Pu and measurement of isotope ratio simultaneously. The contribution of (238)U
      from both spikes and samples was minimized by careful chemical separation and
      optimization of spike concentration. The (238)U(1)H and tail contribution on
      (239)Pu peak were about 0.75 x 10(-5) and 1 x 10(-5) of (238)U intensity,
      respectively, and they were corrected from (239)Pu using externally determined
      ((238)U(1)H + tailing)/(238)U ratio and (238)U measurement during acquisition.
      The detection limits of this analytical procedure were 0.61 fg/ml and 0.56 fg/ml
      for (239)Pu and (240)Pu, respectively (4 nBq/m(3) and 12 nBq/m(3) for (239)Pu and
      (240)Pu, respectively). The precision of isotope ratio measurement was better
      than 2% for larger quantity than 20 fg of (239)Pu. In spring, maximum
      concentration of 0.580 microBq/m(3) for (239)Pu and 0.404 microBq/m(3) for
      (240)Pu was observed when Al concentration was maximum, so called as Yellow Sand
      event. Pu concentrations in aerosols are well correlated with Al, a tracer of
      soil dust. The ratios of Pu/Al were 0.0082 (microBq/microg) and 0.0055
      (microBq/microg) for (239)Pu/Al and (240)Pu/Al, respectively. Isotope ratios of
      Pu ((240)Pu/(239)Pu) in Yellow Sand samples show 0.191+/-0.014 close to those of
      global fallout. These facts indicate that Yellow Sand plays an important role in
      the behavior of Pu in the environment like other concomitant metals such as Al,
      Fe etc.

PMID- 16962163
TI  - Expression of the epidermal growth factor system in endometrioid endometrial
      cancer.
AB  - OBJECTIVE: The Epidermal Growth Factor (EGF) system is expressed in healthy
      premenopausal endometrium. We describe the expression of the four receptors,
      HER1, HER2, HER3, HER4 and the six ligands amphiregulin, transforming growth
      factor alpha (TGF-alpha), heparin binding EGF like growth factor (HB-EGF),
      betacellulin, epiregulin and EGF in endometrioid endometrial cancer. METHODS: We
      have uterine samples from 45 women with endometrioid endometrial cancer. As
      normal counterparts, endometrial samples from thirteen postmenopausal women, and
      previous data on fourteen premenopausal women were employed. Extracted RNA was
      analyzed by real-time PCR; the receptors and ligands were localized by
      immunohistochemistry. RESULTS: Three receptors (HER1, HER2 and HER4) and two
      detectable ligands (TGF-alpha and HB-EGF) are expressed significantly higher in
      endometrial cancer than in healthy postmenopausal endometrium. Cancer tissue show
      significantly lower expression of HER1 and HER3, and higher expression of HER4,
      amphiregulin, TGF-alpha and HB-EGF compared to premenopausal endometrium; no
      difference is seen in HER2. EGF is undetectable in all of the samples.
      Immunohistochemically the receptors locate to the epithelium and/or glands while
      the ligands locate to the stroma (amphiregulin), the stroma and the epithelium
      (TGF-alpha, epiregulin), the epithelium (betacellulin) or are not detectable (HB
      EGF, EGF). CONCLUSIONS: mRNA of all receptors and five ligands are present in
      endometrioid endometrial cancer, and the protein of all receptors and four
      ligands are identified by immunohistochemistry. The expression pattern in
      endometrioid endometrial cancer differs from the pattern in pre- and
      postmenopausal endometrium. The most remarkable finding is an increased level of
      HER4, a receptor which correlates to a favorable prognosis in other types of
      cancers.

PMID- 16962164
TI  - Evaluation of intrauterine antibiotic treatment of clinical metritis and retained
      fetal membranes in dairy cows.
AB  - Retained fetal membranes (RFM) and clinical metritis (CM) are frequently
      diagnosed disease conditions in dairy cows and considered of major economic
      impact due to negative effect on reproduction and milk production. The objective
      of this study was to evaluate the efficacy of i.u. tetracycline for the treatment
      of RFM and CM in dairy cows. Affected cows were randomly assigned to two groups;
      treatment group animals received i.u. 5g chlortetracycline twice weekly for 2
      wks, and no treatment group. A total of 1416 cows and 804 heifers in 5 herds
      calved during the study period. CM was diagnosed in 18.6% (inter farm range; 15.2
      23.5%) and 30% (19.4-42.3%) of cows and heifers, respectively. RFM was diagnosed
      in 13.1% (9.4-18.1%) and 9.2% (3.6-13.8%) of cows and heifers, respectively.
      Conception rates after first insemination were 38.3%, 42.5% and 18% in normal,
      treated and non-treated CM cows, respectively. Numbers of days open were 140.5,
      136.2 and 165.5 in normal, treated and non-treated CM cows, respectively. Based
      on 305-d corrected milk yield, cows and heifers affected by RFM and CM produced
      300-500kg less milk compared with their normal herd mates. Cows treated for CM
      produced 654kg more milk per 305-d corrected lactation compared to non-treated
      control cows. Treatment of RFM had no effect on reproductive performance or milk
      production. In conclusion, i.u. chlortetracycline treatment was proven to prevent
      the detrimental effect of CM on reproductive performance in heifers and cows and
      on milk production in cows only.

PMID- 16962165
TI  - The effect of homologous prostatic fluid on motility and morphology of dog
      epididymal spermatozoa extended and frozen in Biladyl with Equex STM paste or
      Andromed.
AB  - Although dog prostatic fluid decreases the longevity of ejaculated dog
      spermatozoa, it also increases their rate of motility and their fertility after
      vaginal insemination, as well as the fertility of epididymal spermatozoa after
      uterine insemination. These findings indicate a need to further characterize the
      effects of prostatic fluid on dog spermatozoa. This study was done to determine
      the effects (P<0.05) of homologous prostatic fluid added prior to cooling, after
      thawing, or at both times to epididymal spermatozoa from 21 dogs. The effects of
      two extenders were also determined. The one extender was Biladyl(*) with Equex
      STM paste(**) (BilEq) and the other Andromed(*) (Minitub, Tiefenbach, Germany
      (*); Nova Chemical Sales, Scituate, MA, USA (**)). The response variables were
      percentage progressively motile spermatozoa (Prog) and morphology after thawing.
      Prog was measured at various times until 8h after extension (unfrozen
      spermatozoa) or until 2h after thawing. Prog after thawing was higher with BilEq
      than Andromed, when no prostatic fluid was added prior to cooling, and when
      prostatic fluid was added after thawing. BilEq resulted in a higher mean
      percentage of spermatozoa with bent principle pieces than Andromed and the
      addition of prostatic fluid prior to cooling resulted in lower mean percentages
      of cytoplasmic droplets and bent principle pieces than when none was added. The
      optimal combination was BilEq with prostatic fluid added prior to cooling (in
      order to inhibit the development of bent principle pieces) and after thawing (to
      achieve higher motility until 1h after thawing). This study shows that BilEq is
      more suitable for the freezing of epididymal spermatozoa than Andromed and that
      prostatic fluid improves the freezability and post-thaw longevity of epididymal
      spermatozoa frozen in BilEq.

PMID- 16962166
TI  - The relationship between psychopathic traits measured by the Youth Psychopathic
      trait Inventory and psychopathology in a UK sample of conduct disordered boys.
AB  - The Youth Psychopathy traits Inventory (YPI) is a newly developed self-report
      measure of psychopathy. There are no studies looking at the validity of this
      measure in UK samples. We assessed 115 male adolescents (mean age 16.22 years)
      with DSM-IV conduct disorder on a range of measures including the YPI, Child
      Behaviour Checklist (CBCL) and the Impulsivity-Venturesomeness-Empathy
      Questionnaire (IVE). The YPI had showed the expected positive correlations with
      aggression, delinquency and impulsivity. The YPI was able to identify a
      "psychopathic-like" subgroup with higher impulsive/aggressive and delinquent
      scores and lower empathy. The YPI may be of value as a screening tool for cases
      that require further assessment and evaluation using interview based measures of
      psychopathic traits.

PMID- 16962167
TI  - Long-term stable fibrin gels for cartilage engineering.
AB  - It is essential that hydrogel scaffold systems maintain long-term shape stability
      and mechanical integrity for applications in cartilage tissue engineering. Within
      this study, we aimed at the improvement of a commercially available fibrin gel in
      order to develop a long-term stable fibrin gel and, subsequently, investigated
      the suitability of the optimized gel for in vitro cartilage engineering. Only
      fibrin gels with a final fibrinogen concentration of 25mg/ml or higher, a Ca(2+)
      concentration of 20mm and a pH between 6.8 and 9 were transparent and stable for
      three weeks, the duration of the experiment. In contrast, when preparing fibrin
      gels with concentrations out of these ranges, turbid gels were obtained that
      shrank and completely dissolved within a few weeks. In rheological
      characterization experiments, the optimized gels showed a broad linear
      viscoelastic region and withstood mechanical loadings of up to 10,000 Pa. Bovine
      chondrocytes suspended in the optimized fibrin gels proliferated well and
      produced the extracellular matrix (ECM) components glycosaminoglycans and
      collagen type II. When initially seeding 3 million cells or more per construct
      (5mm diameter, 2mm thick), after 5 weeks of culture, a coherent cartilaginous ECM
      was obtained that was homogenously distributed throughout the whole construct.
      The developed fibrin gels are suggested also for other tissue engineering
      applications in which long-term stable hydrogels appear desirable.

PMID- 16962169
TI  - Nuclear calcium signals during L-LTP induction do not predict the degree of
      synaptic potentiation.
AB  - The magnitude and/or duration of nuclear Ca(2+)-transients has been shown to dose
      dependently modulate gene transcription upon neuronal activation. This is an
      attractive model for synapse-to-nucleus communication. In order to encode
      synaptic information, these nuclear Ca(2+)-transients have to be correlated with
      changes in synaptic strength rather than changes in gene expression patterns. In
      this study, we analysed nuclear Ca(2+) signals during L-LTP induction. Using a
      combined approach of fEPSP recordings and two-photon imaging, these Ca(2+)
      signals were correlated with different degrees of synaptic potentiation in CA1
      hippocampal slices. To refine our analysis on the single-cell level, we developed
      a new approach called single-cell-excitability-probing (SCEP) to assay the
      plasticity outcome of individual cells by optical means. The degrees of synaptic
      potentiation we observed could be categorized into transcription independent,
      transcription-dependent and reduced transcription-dependent. There is no
      consistent dose-dependent relationship between these different degrees of
      synaptic potentiation and the magnitude, the decay time and the area under the
      curve of nuclear Ca(2+)-transients during L-LTP induction. This indicates that
      nuclear Ca(2+)-transients during induction are unsuited to grade the degree of
      plasticity in an analogue manner. We propose a role for nuclear Ca(2+) as a
      digital on/off switch for activating transcription.

PMID- 16962168
TI  - Biofunctionalization of collagen for improved biological response: scaffolds for
      corneal tissue engineering.
AB  - Residual dendrimer amine groups were modified with incorporate COOH group
      containing biomolecules such as cell adhesion peptides into collagen scaffolds.
      YIGSR, as a model cell adhesion peptide, was incorporated into both the bulk
      structure of the gels and onto the gel surface. The effects of the peptide
      modified collagen gels on corneal epithelial cell behavior were examined with an
      aim of improving the potential of these materials as tissue-engineering
      scaffolds. YIGSR was first chemically attached to dendrimers and the YIGSR
      attached dendrimers were then used as collagen crosslinkers, incorporating the
      peptide into the bulk structure of the collagen gels. YIGSR was also attached to
      the surface of dendrimer crosslinked collagen gels through reaction with excess
      amine groups. The YIGSR modified dendrimers were characterized by H-NMR and MALDI
      mass spectra. The amount of YIGSR incorporated into collagen gels was determined
      by (125)I radiolabelling at maximum to be 3.1-3.4 x 10(-2)mg/mg collagen when
      reacted with the bulk and 88.9-95.6 microg/cm(2) when attached to the surface.
      The amount of YIGSR could be tuned by varying the amount of peptide reacted with
      the dendrimer or the amount of modified dendrimer used in the crosslinking
      reaction. It was found that YIGSR incorporation into the bulk and YIGSR
      modification of surface promoted the adhesion and proliferation of human corneal
      epithelial cells as well as neurite extension from dorsal root ganglia.

PMID- 16962170
TI  - Regular analgesic use and risk of multiple myeloma.
AB  - Analgesic use has been implicated in the chemoprevention of a number of solid
      tumors, but to date no previous research has focused on the role of analgesics in
      the etiology of multiple myeloma (MM). We conducted a hospital-based case-control
      study of 117 patients with primary, incident MM and 483 age and residence matched
      controls without benign or malignant neoplasms. All participants received medical
      services at Roswell Park Cancer Institute in Buffalo, NY, and completed a
      comprehensive epidemiological questionnaire. Participants who reported analgesic
      use at least once a week for at least 6 months were classified as regular users;
      individuals who did not use analgesics regularly served as the reference group
      throughout the analyses. We used unconditional logistic regression analyses to
      compute crude and adjusted odds ratios (ORs) with corresponding 95% confidence
      intervals (CIs). Compared to non-users, regular aspirin users were not at reduced
      risk of MM (adjusted OR=0.99; 95% CI 0.65-1.49), nor were participants with the
      highest frequency or duration of aspirin use. A significant risk elevation was
      found for participants who were regular acetaminophen users (adjusted OR=2.95;
      95% CI 1.72-5.08). Further, marked increases in risk of MM were noted with both
      greater frequency (>7 tablets weekly; adjusted OR=4.36; 95% CI 1.70-11.2) and
      greater duration (>10 years; adjusted OR=3.26; 95% CI 1.52-7.02) of acetaminophen
      use. We observed no evidence of a chemoprotective effect of aspirin on MM risk,
      but observed significant risk elevations with various measures of acetaminophen
      use. Our results warrant further investigation in population-based case-control
      and cohort studies and should be interpreted with caution in light of the limited
      sample size and biases inherent in hospital-based studies.

PMID- 16962171
TI  - Confirmatory factor analysis of the Child Abuse Potential Inventory: results
      based on a sample of Chinese mothers in Hong Kong.
AB  - OBJECTIVES: To evaluate whether or not the original six-factor structure of the
      Child Abuse Potential (CAP) Inventory suggested by [Milner, J.S. (1986). The
      Child Abuse Potential Inventory: Manual (2nd ed.). DeKalb, IL: Psytec. Inc.] can
      be confirmed with data from a group of Chinese mothers in Hong Kong. METHOD:
      Eight hundred and ninety-seven mothers from 13 child care centers in Hong Kong
      successfully completed a set of structured questionnaires consisting, among
      others, of the 77-item Abuse Scale of the CAP Inventory. A confirmatory factor
      analysis (CFA) was performed to determine whether the data fits the factorial
      structure of the CAP Inventory identified by Milner (1986). RESULTS: The root
      mean square error of approximation (RMSEA) of the model epsilona) is 0.031,
      indicating a close fit of the model in relation to the degrees of freedom. On
      testing the close fit against the null hypothesis that Ho: epsilona<or=0.05, the
      associated p-value is almost one. This suggests that the probability that Ho is
      true is extremely high. The estimated expected value of the cross-validation
      index (ECVI) is 6.185, which is less than the ECVIsat (6.703), giving another
      indication on the fitness of the model. Other fit indices also provide support
      for the model fitness. CONCLUSION: The original six-factor structure of the CAP
      Inventory tested by CFA is acceptable. The theoretical constructs underlying the
      CAP Inventory are supported by data collected from Chinese mothers in Hong Kong.

PMID- 16962172
TI  - The "geography" of child maltreatment in Israel: Findings from a national data
      set of cases reported to the social services.
AB  - OBJECTIVES: This article examines the "geography" of reported cases of child
      maltreatment in Israel by determining its frequency and rates according to
      nationality, area of residence, and size and type of locality. METHOD: The study
      collected data at the local level in Israel based on reports to social services
      of cases of child maltreatment during 2000; locality is the unit of analysis.
      RESULTS: The rate of reported cases of child maltreatment was 17.8 per 1,000
      children in Israel in 2000. The rates varied, however, among different
      localities. They were lower in Arab localities (9 per 1,000 children) than in the
      Jewish ones (20 per 1,000), higher in large cities and other socioeconomic
      affluent localities (19 per 1,000), and varied according to the geographic area.
      CONCLUSIONS: This study demonstrates considerable variation in rates of reported
      cases of child maltreatment by locality and by population makeup. Thus, to
      fulfill the Israeli legislation of mandatory reporting of any reasonable
      suspicion of child maltreatment, the state should better develop policies and
      services that encourage reporting of child maltreatment among the Arab and
      ultraorthodox populations and in smaller or socioeconomic disadvantaged
      localities. Furthermore, the social services must build a bridge to the minority
      populations in Israel, developing their trust in these services and increasing
      their propensity to use them.

PMID- 16962173
TI  - Fetal alcohol spectrum disorders: a practical clinical approach to diagnosis.
AB  - In utero exposure to alcohol can have numerous adverse effects on a developing
      fetus. These effects represent a spectrum of structural anomalies and
      neurocognitive and behavioral disabilities that have recently been termed fetal
      alcohol spectrum disorders (FASD). Children at the most severe end of this
      spectrum and displaying the complete phenotype of characteristic facial
      anomalies, growth retardation and developmental abnormalities of the central
      nervous system are defined as having fetal alcohol syndrome (FAS). While FAS is
      the most readily clinically recognized form of FASD, other categories within the
      continuum of adverse effects due to prenatal alcohol exposure are becoming better
      defined. These include partial fetal alcohol syndrome (PFAS), alcohol-related
      birth defects (ARBD) and alcohol-related neurodevelopmental disorder (ARND). As
      more is learned regarding the exact manifestations of alcohol on brain
      development, these classifications may be expanded and/or refined. Because FASD
      represents a major public health concern, early recognition of at-risk children
      is important for initiating interventional strategies. Thus, the purpose of this
      report is to educate practicing physicians about the recognizable phenotypes of
      FASD in order to accurately identify these children and implement the most
      appropriate management plans.

PMID- 16962174
TI  - Incidence of eyelid cancers in Taiwan: a 21-year review.
AB  - PURPOSE: To describe the epidemiologic characteristics and incidence trends of
      primary eyelid cancers in the Chinese population in Taiwan between 1979 and 1999.
      DESIGN: Retrospective population-based cancer registry data review. PARTICIPANTS:
      A total of 1166 primary eyelid cancers coded to International Classification of
      Diseases 8 or 9, site 172.1 (malignant melanoma of eyelid) and 173.1 (other
      malignant neoplasm of eyelid) were retrieved from the Taiwan National Cancer
      Registry between January 1979 and December 1999. Of these, 1121 (96.1%) were
      histopathologically verified and were used for analysis. METHODS: Age- and gender
      specific incidence rates were calculated and were age-adjusted to the 2000 world
      standard population. Trends in incidence rates were estimated by calculating the
      annual percentage change. We further examined the effects of age, period of
      diagnosis, and birth cohort on incidence trends using age-period-cohort analysis.
      MAIN OUTCOME MEASURE: Age-standardized incidence rate. RESULTS: The mean age at
      diagnosis of eyelid cancers was 62.6+/-14.1 years. The average annual age
      standardized incidence rate was 3.2 per million during the study period. There
      was an overall increase of incidence rates from 1.5 per million in 1979 to 5.1
      per million in 1999, with an annual percentage change of 4.63% (P<0.001). The
      most common eyelid malignancy was basal cell carcinoma (BCC; 65.1%), followed by
      squamous cell carcinoma (12.6%), and sebaceous cell carcinoma (7.9%). The
      increasing rates were mainly driven by an increase in the incidence of BCC.
      Cohort effects were found to play a major role in terms of model fit for the
      incidence trends of BCC. CONCLUSIONS: These national data reveal a rapidly
      increasing incidence of eyelid cancers from 1979 to 1999 in Taiwan. Basal cell
      carcinoma dominates the incidence trends, and the significant cohort effects give
      a warning of increasing risk of BCC in younger birth cohorts.

PMID- 16962175
TI  - Prevalence and correlates of children's diagnosed eye and vision conditions.
AB  - PURPOSE: Little is known about the distribution of eye and vision conditions
      among children and about possible disparities in the distribution of these
      conditions. The purpose of this report is to describe the prevalence of diagnosed
      eye and vision conditions among children younger than 18 years in the United
      States. DESIGN: Repeated population-based cross-sectional study. PARTICIPANTS:
      Forty-eight thousand three hundred four members of randomly selected households
      in the U.S. who were younger than 18 years in the years 1996 through 2001 were
      analyzed. METHODS: The prevalence of children with diagnosed eye and vision
      conditions was estimated using self-reported information from the nationally
      representative Medical Expenditure Panel Surveys (MEPS) for 1996 through 2001.
      Descriptive statistics are presented, and the associations between the likelihood
      of diagnosed eye and vision conditions and child and family characteristics were
      assessed using logistic regression analyses adjusted for the complex survey
      design of MEPS. MAIN OUTCOME MEASURES: Prevalence of diagnosed eye and vision
      conditions and measures of the association between diagnosed eye and vision
      conditions and child and family characteristics. RESULTS: On average,
      approximately 6.8% (95% confidence interval [CI], 6.4%-7.2%) of children < 18
      years in the U.S. have a diagnosed eye and vision condition, ranging from 8.6%
      (95% CI, 7.8%-9.5%) in 1996 to 5.8% (95% CI, 5.2%-6.4%) in 2001. Excluding
      conjunctivitis, the 4 most common conditions were refractive disorders,
      potentially blinding disorders, trauma or injury, and other disorders not
      elsewhere classified. White children, children with more educated mothers, and
      children living in higher income families were more likely to have a diagnosed
      eye and vision condition. Hispanic children, children in very good or excellent
      health, and uninsured children were less likely to have any self-reported
      diagnosed eye and vision condition. CONCLUSIONS: This article presents a method
      for using MEPS to identify children younger than 18 years with eye and vision
      conditions. Although this method does not identify all children with eye and
      vision conditions, it does identify children with diagnosed eye and vision
      conditions. Results provide some evidence that underprivileged children may be
      underdiagnosed, undertreated, or both, placing them at risk for future problems.

PMID- 16962176
TI  - Neuropsychiatric symptoms and past manganese exposure in a ferro-alloy plant.
AB  - INTRODUCTION: Psychiatric manifestations have been reported in cases of
      manganism, and mood disorders are often observed in manganese (Mn) exposed
      workers. We examined neuropsychiatric symptoms among formerly Mn-exposed workers
      14 years after cessation of exposure. MATERIALS AND METHODS: A study was
      conducted in 1990 among workers from a ferro- and silico-Mn plant and unexposed
      working men referents from the same region in South-West Quebec. At follow-up in
      2004, 77 former Mn-workers and 81 referents agreed to participate and responded
      to a neuropsychiatric symptom checklist, the Brief Symptom Inventory (BSI);
      scores were transformed into T-scores based on a normative population. Cumulated
      exposure indices (CEI) were computed for each former Mn-worker. Linear and
      logistic regression analyses were used. RESULTS: Mean T-scores were significantly
      higher among former Mn-workers than referents on scales of Depression and
      Anxiety. Mean T-scores of psychological distress increased with the CEI tertiles,
      with significant associations for the scales Somatization, Depression, Anxiety
      and Hostility. Former Mn-workers in the two highest tertiles of CEI showed a
      higher risk for T-scores >or=63 for Hostility (OR, 7.5; 95% CI, 1.5-38.9),
      Depression (OR, 2.6; 95% CI, 1.1-8.4) and Anxiety (OR, 3.0; 95% CI, 1.1-8.4).
      CONCLUSION: These results suggest that past exposure to Mn may have lasting
      consequences on neuropsychiatric symptoms.

PMID- 16962177
TI  - Kraepelinian subtype and deficit syndrome in chronic schizophrenia.
AB  - The present study examined the clinical overlap between the Kraepelinian and
      deficit subtypes of schizophrenia. A total of 103 patients with schizophrenia
      were divided into four groups on the basis of the presence or absence of the two
      classifications, and the demographic and clinical characteristics of the groups
      were statistically compared. There was a significant overlap of Kraepelinian and
      deficit status, but nevertheless the retention of both classifications appears to
      be justified.

PMID- 16962178
TI  - Isolation of methicillin resistant Staphylococcus aureus from the surface and
      core of tonsils in children.
AB  - BACKGROUND: The rate of recovery methicillin resistant Staphylococcus aureus
      (MRSA) in tonsils that were removed because of recurrent Group A-beta-hemolytic
      streptococci (GABHS) tonsillitis was not previously reported. MRSA may serve as a
      potential source for the spread of these organisms to other body sites as well to
      other individuals. This study investigated the rate of recovery of MRSA as well
      as other aerobic organisms from tonsils that were removed because of recurrent
      GABHS infection. PATIENTS AND METHODS: Core and surface tonsillar cultures for
      aerobic bacteria were obtained from 44 children who had tonsillectomy because of
      recurrent GABHS tonsillitis. RESULTS: A total of 167 aerobic isolates were
      recovered from the core of the tonsils (3.8/specimen) and 151 (3.4/specimen) were
      isolated from the surface. The predominant isolates were alpha-hemolytic
      streptococci, GABHS, S. aureus, gamma-hemolytic streptococci, Haemophilus
      influenzae and Moraxella catarrhalis. Concordance in the recovery of all
      organisms was noted in 117 instances. Certain organisms (i.e. GABHS, S. aureus)
      were recovered more often from the tonsillar cores, where other (i.e. alpha
      hemolytic streptococci, gamma-hemolytic streptococci) were recovered more often
      from the tonsillar surface. Forty-four beta-lactamase-producing bacteria (BLPB)
      were recovered from 32 (75%) of the tonsillar cores, and 28 were isolated from 23
      (52%) of the tonsillar surfaces. The predominant BLPB were S. aureus, H.
      influenzae and M. catarrhalis. Seven isolates of MRSA were recovered from the
      cores and two were isolated from the surface. Five of the core isolates and the
      two surface isolates were also BLPB. All of the MRSA isolates were resistant to
      oxacillin, penicillin and erythromycin and were susceptible to clindamycin,
      trimethoprim-sulfamethoxazole and vancomycin. CONCLUSIONS: These data
      demonstrated that in recurrently GABHS infected tonsils, BLPB was recovered from
      over 75% of the tonsillar cores, core tonsillar cultures yielded more GABHS and
      S. aureus, and MRSA was isolated from 16% of the tonsils.

PMID- 16962179
TI  - Pulmonary arterial pressure in infants with laryngomalacia.
AB  - OBJECTIVE: Persistent upper airway obstruction may lead to increased pulmonary
      arterial pressure in childhood. Laryngomalacia is one of the most common causes
      of transient upper airway obstruction by laryngeal blockage in infants. The aim
      of the study is to evaluate the pulmonary arterial pressures in infants with
      laryngomalacia during infancy period. METHODS: Fifteen infants with
      laryngomalacia and 30 healthy controls were enrolled into this study. The
      pulmonary arterial pressures were measured by using Doppler echocardiography.
      Infants were also evaluated by clinical investigations, telecardiography and
      electrocardiography. RESULTS: Our results showed that infants with laryngomalacia
      may have significantly higher pulmonary arterial pressure than healthy subjects.
      Pressures of patient group were significantly decreased at the end of infancy
      period. CONCLUSIONS: Increased pulmonary arterial pressure levels due to
      laryngomalacia are reversible by during developmental process. Therefore, in
      symptomatic period, evaluation of infants with laryngomalacia by using Doppler
      echocardiography may be useful for monitoring pulmonary arterial pressure and
      following up the clinical outcome.

PMID- 16962180
TI  - Real-time PCR quantitation of hepatitis B virus total DNA and covalently closed
      circular DNA in peripheral blood mononuclear cells from hepatitis B virus
      infected patients.
AB  - It remains unclear whether hepatitis B virus (HBV) replicates in extrahepatic
      tissues, and particularly in peripheral blood mononuclear cells (PBMCs), which
      may serve as a reservoir for the maintenance of infection. A real-time PCR assay
      for the quantitation of total and covalently closed circular (ccc) HBV DNA in
      serum and in PBMCs was developed. This assay was highly sensitive (detection
      limit: 27 IU/mL), linear over a wide range (9 log10), and was displayed high
      inter- and intra-assay reproducibility for the quantitation of total DNA.
      Genotypes A to E were detected and the results were consistent with those
      obtained with the COBAS Amplicor HBV Monitor Test. The specificity of the
      methodology was increased by prior treatment with an enzyme that digests relaxed
      circular DNA, and the elimination of background signals from virus adsorbed to
      the surface of PBMCs. HBV DNA was detected in the serum and PBMCs of 12 HBsAg
      positive patients, with less than 1% in the cccDNA form. In conclusion, the
      quantitation of total and ccc HBV DNA in PBMCs is potentially useful as a non
      invasive marker, and may help to increase our knowledge of the natural history of
      hepatitis B.

PMID- 16962181
TI  - Interaction of raclopride and preparatory interval effects on simple reaction
      time performance.
AB  - In a series of three experiments, simple reaction time (RT) was characterized
      with respect to a variable preparatory interval (PI) in order to investigate the
      relationship between interval timing and RT. In Experiment 1, it was shown that
      RT decreases as a function of PI and that this effect varies with amount of
      training. In Experiment 2, RT was shown to increase during probe trials that used
      a novel 6.25s PI, suggesting that the specific durations of the PIs encoded
      during initial training contribute to the PI effect on RT. In Experiment 3, 100
      microg/kg i.p. of raclopride proportionally slowed RT as a function of the PI.
      These results are discussed within the context of neuropsychological models of
      interval timing and support an underlying role for cortico-striatal dopaminergic
      function in temporal processing and simple RT measurements.

PMID- 16962182
TI  - DNA binding and transactivation properties of the Schistosoma mansoni
      constitutive androstane receptor homologue.
AB  - SmCAR (Schistosoma mansoni constitutive androstane receptor) is a schistosome
      homologue of the CAR/PXR/VDR group of nuclear receptors. The P box sequence in
      the DNA binding domain (DBD) of SmCAR, which is essential in determining the DNA
      binding specificity of nuclear receptors, is different from its vertebrate
      homologues. Previous data demonstrates that SmCAR binds to a hormone response
      element containing a single half site AGTGCA as a monomer. SmRXR1 and SmRXR2 are
      two S. mansoni homologues of vertebrate retinoid X receptors (RXRs). RXRs usually
      heterodimerize with various nuclear receptors. Yeast-two hybrid analyses, in
      vitro pull-down and co-immunoprecipitation assays demonstrated that SmCAR
      interacts with SmRXR1 but not SmRXR2. Using chimeras consisting of the DBD of
      SmCAR and the ligand binding domain (LBD) of mouse (m) CAR, we show that despite
      a different P box, SmCAR DBD shares DNA binding specificity with mCAR. However,
      the SmCAR DBD does exhibit some of the DNA binding properties specific to SmCAR.
      Studies of the chimeras also demonstrated that the SmCAR DBD is able to
      heterodimerize with the DBD of human RXR, allowing high affinity DNA binding.
      Based on this study and previous results, we conclude that SmCAR may recognize
      its cognate hormone response element via two mechanisms: binding to DNA
      monomerically or heterodimerizing with SmRXR1. We also demonstrate that a
      transcription activation function-1 (AF-1) is located in the SmCAR A/B domain.

PMID- 16962183
TI  - Biochemical characterization of Trypanosoma brucei RNA polymerase II.
AB  - In Trypanosoma brucei, transcription by RNA polymerase II accounts for the
      expression of the spliced leader (SL) RNA and most protein coding mRNAs. To
      understand the regulation of RNA polymerase II transcription in these parasites,
      we have purified a transcriptionally active enzyme through affinity
      chromatography of its essential subunit, RPB4. The enzyme preparation is active
      in both promoter-independent and promoter-dependent in vitro transcription
      assays. Importantly, the enzyme is sensitive to alpha-amanitin inhibition, a
      hallmark of eukaryotic RNA polymerase II enzymes. Using mass spectrometric
      analysis we have identified the previously unobserved RPB12 subunit of T. brucei
      RNA polymerase II. TbRPB12 contains a conserved CX(2)CX(10-15)CX(2)C zinc binding
      motif that is characteristic of other eukaryotic RPB12 polypeptides. We also
      identified seven proteins that associate with T. brucei RNA polymerase II. While
      both bioinformatics and biochemical analysis have focused on the subunit
      structure of trypanosome RNA polymerases, this is the first study that reveals a
      functional RNA polymerase II enzyme.

PMID- 16962185
TI  - Actin based processes that could determine the cytoplasmic architecture of plant
      cells.
AB  - Actin polymerisation can generate forces that are necessary for cell movement,
      such as the propulsion of a class of bacteria, including Listeria, and the
      protrusion of migrating animal cells. Force generation by the actin cytoskeleton
      in plant cells has not been studied. One process in plant cells that is likely to
      depend on actin-based force generation is the organisation of the cytoplasm. We
      compare the function of actin binding proteins of three well-studied mammalian
      models that depend on actin-based force generation with the function of their
      homologues in plants. We predict the possible role of these proteins, and thus
      the role of actin-based force generation, in the production of cytoplasmic
      organisation in plant cells.

PMID- 16962184
TI  - Genome-wide analyses show that nuclear and cytoplasmic RNA levels are
      differentially affected by dioxin.
AB  - The aryl hydrocarbon receptor (AHR) mounts the body's main molecular defense
      against environmental toxicants by inducing a battery of genes encoding
      xenobiotic metabolizing proteins. The AHR is activated by polycyclic aromatic
      hydrocarbon toxicants, including the pervasive teratogen and carcinogen 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD or dioxin). The TCDD-activated AHR
      significantly changes the cytoplasmic mRNA levels of hundreds of genes, but
      little is known of the mechanism by which the activated AHR causes such a strong
      effect on global gene expression. We used high-density microarrays to compare
      nuclear and cytoplasmic RNA levels from untreated and TCDD-treated mouse
      embryonic fibroblasts (MEF) to test the hypotheses that (1) TCDD has a large
      impact on nuclear RNA levels and (2) that cytoplasmic RNA levels are dependent on
      nuclear RNA levels. We found that nuclear RNA levels are strongly affected by
      TCDD, and that nuclear and cytoplasmic RNA levels are only weakly correlated,
      indicating that other regulatory mechanisms are controlling cytoplasmic RNA
      levels. The nuclear RNAs most affected by TCDD encode proteins involved in
      nuclear RNA processing and transcription. We conclude that although the AHR
      regulates key xenobiotic metabolizing genes at the transcriptional level, a
      larger impact of the TCDD-activated AHR may be at post-transcriptional levels.

PMID- 16962186
TI  - Ca2+ signaling and early embryonic patterning during the blastula and gastrula
      periods of zebrafish and Xenopus development.
AB  - It has been proposed that Ca(2+) signaling, in the form of pulses, waves and
      steady gradients, may play a crucial role in key pattern forming events during
      early vertebrate development [L.F. Jaffe, Organization of early development by
      calcium patterns, BioEssays 21 (1999) 657-667; M.J. Berridge, P. Lipp, M.D.
      Bootman, The versatility and universality of calcium signaling, Nat. Rev. Mol.
      Cell Biol. 1 (2000) 11-21; S.E. Webb, A.L. Miller, Calcium signalling during
      embryonic development, Nat. Rev. Mol. Cell Biol. 4 (2003) 539-551]. With
      reference to the embryos of zebrafish (Danio rerio) and the frog, Xenopus laevis,
      we review the Ca(2+) signals reported during the Blastula and Gastrula Periods.
      This developmental window encompasses the major pattern forming events of
      epiboly, involution, and convergent extension, which result in the establishment
      of the basic germ layers and body axes [C.B. Kimmel, W.W. Ballard, S.R. Kimmel,
      B. Ullmann, T.F. Schilling, Stages of embryonic development of the zebrafish,
      Dev. Dyn. 203 (1995) 253-310]. Data will be presented to support the suggestion
      that propagating waves (both long and short range) of Ca(2+) release, followed by
      sequestration, may play a crucial role in: (1) Coordinating cell movements during
      these pattern forming events and (2) Contributing to the establishment of the
      basic embryonic axes, as well as (3) Helping to define the morphological
      boundaries of specific tissue domains and embryonic structures, including future
      organ anlagen [E. Gilland, A.L. Miller, E. Karplus, R. Baker, S.E. Webb, Imaging
      of multicellular large-scale rhythmic calcium waves during zebrafish
      gastrulation, Proc. Natl. Acad. Sci. USA 96 (1999) 157-161; J.B. Wallingford,
      A.J. Ewald, R.M. Harland, S.E. Fraser, Calcium signaling during convergent
      extension in Xenopus, Curr. Biol. 11 (2001) 652-661]. The various potential
      targets of these Ca(2+) transients will also be discussed, as well as how they
      might integrate with other known pattern forming pathways known to modulate early
      developmental events (such as the Wnt/Ca(2+)pathway; [T.A. Westfall, B. Hjertos,
      D.C. Slusarski, Requirement for intracellular calcium modulation in zebrafish
      dorsal-ventral patterning, Dev. Biol. 259 (2003) 380-391]).

PMID- 16962187
TI  - Toxicity of enzymatic oxidation products of spermine to human melanoma cells
      (M14): sensitization by heat and MDL 72527.
AB  - In situ formation of cytotoxic metabolites by an enzyme-catalyzed reaction is a
      recent approach in cancer chemotherapy. We demonstrate that multidrug resistant
      human melanoma cells (M14 ADR) are more sensitive than the corresponding wild
      type cells (M14 WT) to hydrogen peroxide and aldehydes, the products of bovine
      serum amine oxidase (BSAO)-catalyzed oxidation of spermine. Hydrogen peroxide was
      mainly responsible for the loss of cell viability. With about 20%, the aldehydes
      formed from spermine contribute also to cytotoxicity. Elevation of temperature
      from 37 degrees C to 42 degrees C decreased survival of both cell lines by about
      one log unit. Pre-treatment with N1,N4-bis(2,3-butadienyl)-1,4-butanediamine (MDL
      72527), a lysosomotropic compound, sensitized cells to toxic spermine
      metabolites. MDL 72527 (at 300 microM) produced in M14 cells numerous cytoplasmic
      vacuoles which, however, disappeared by 24 h, even in the presence of the drug.
      Mitochondrial damage, as observed by transmission electron microscopy, correlated
      better with the cytotoxic effects of the treatment than vacuole formation. Since
      the release of lysosomal enzymes causes oxidative stress and apoptosis, we
      suggest that the lysosomotropic effect of MDL 72527 is the major reason for its
      sensitizing effect.

PMID- 16962188
TI  - Differential regulation of lipopolysaccharide and Gram-positive bacteria induced
      cytokine and chemokine production in splenocytes by Galphai proteins.
AB  - Heterotrimeric Gi proteins play a role in lipopolysaccharide (LPS) and
      Staphylococcus aureus (SA) activated signaling leading to inflammatory mediator
      production. We hypothesized that genetic deletion of Gi proteins would alter
      cytokine and chemokine production induced by LPS and SA. LPS- and heat killed SA
      induced cytokine and chemokine production in splenocytes from wild type (WT),
      Galpha(i2) (-/-) or Galpha(i1/3) (-/-) mice were investigated. LPS- or SA-induced
      production of TNFalpha, IL-6, IFNgamma, IL-12, IL-17, GM-CSF, MIP-1alpha, MCP-1,
      MIG and IP-10 were significantly increased (1.2 to 33 fold, p<0.05) in
      splenocytes harvested from Galpha(i2)(-/-) mice compared with WT mice. The effect
      of Galpha(i) protein depletion was remarkably isoform specific. In splenocytes
      from Galpha(i1/3) (-/-) mice relative to WT mice, SA-induced IL-6, IFNgamma, GM
      CSF, and IP-10 levels were decreased (59% to 86%, p<0.05), whereas other LPS- or
      SA-stimulated cytokines and chemokines were not different relative to WT mice.
      LPS- and SA-induced production of KC were unchanged in both groups of the genetic
      deficient mice. Splenocytes from both Galpha(i2) (-/-) and Galpha(i1/3) (-/-)
      mice did not exhibit changes in TLR2 and TLR4 expression. Also analysis of
      splenic cellular composition by flow cytometry demonstrated an increase in
      splenic macrophages and reduced CD4 T cells in both Galpha(i2) (-/-) and
      Galpha(i1/3) (-/-) mice relative to WT mice. The disparate response of
      splenocytes from the Galpha(i2) (-/-) relative to Galpha(i1/3) (-/-) mice
      therefore cannot be attributed to major differences in spleen cellular
      composition. These data demonstrate that G(i2) and G(i1/3) proteins are both
      involved and differentially regulate splenocyte inflammatory cytokine and
      chemokine production in a highly Gi isoform specific manner in response to LPS
      and Gram-positive microbial stimuli.

PMID- 16962189
TI  - An epidemiologic study of late-term abortions in dairy cattle in Denmark, July
      2000-August 2003.
AB  - Abortion in dairy cows in well-managed dairies is not common but differences have
      been reported probably due to variation in animal health, nutrition and
      management, as well as difficulties in observing the aborted material. A 38-month
      study of 507 large Danish dairy herds revealed 3354 late-term abortions and
      224,419 calvings were recorded. During the study period, a total of 3717
      submissions were made to the Danish Institute for Food and Veterinary Research
      (DFVF). A broad spectrum of abortive agents was isolated but none were found to
      be statistically associated with abortions. The number of abortions in a month on
      a dairy was significantly (P<0.001) associated with the number of cows in the
      third trimester but explained only 11% (R(adj)(2)=0.114) of the variability of
      the reported abortions. A total of 23 herds (4.5%) reported 531 abortions
      (15.8%). Although a marginally significant (P=0.11) risk of increased abortions
      was found to exist in bovine viral diarrhea virus- (BVDV) infected herds, it
      could be at least partially explained by additional calvings in those herds.
      Temporal correlation between inseminations and abortions was statistically
      significant (P<0.001) with the highest correlation (r=0.47-0.51) after lagging
      abortions on insemination by 6-8 months. No indication of spatial clustering was
      detected for either specific-abortogenic pathogens or high aborting dairies using
      either Cuzick-Edwards' (P>0.17) or spatial scan tests (P>0.23). Ederer-Myers
      Mantel test was applied to 3 years of data on the highest aborting dairies and
      showed that July had nearly double the expected number of maximum monthly
      abortions (P<0.001). These findings provide further insight into the reported
      abortion pattern in Danish dairies and may facilitate planning future control
      programs.

PMID- 16962190
TI  - Simulating the impact of four control strategies on the population dynamics of
      Neospora caninum infection in Swiss dairy cattle.
AB  - A dynamic deterministic simulation model was developed to assess the impact of
      different putative control strategies on the seroprevalence of Neospora caninum
      in female Swiss dairy cattle. The model structure comprised compartments of
      "susceptible" and "infected" animals (SI-model) and the cattle population was
      divided into 12 age classes. A reference model (Model 1) was developed to
      simulate the current (status quo) situation (present seroprevalence in
      Switzerland 12%), taking into account available demographic and seroprevalence
      data of Switzerland. Model 1 was modified to represent four putative control
      strategies: testing and culling of seropositive animals (Model 2), discontinued
      breeding with offspring from seropositive cows (Model 3), chemotherapeutic
      treatment of calves from seropositive cows (Model 4), and vaccination of
      susceptible and infected animals (Model 5). Models 2-4 considered different sub
      scenarios with regard to the frequency of diagnostic testing. Multivariable Monte
      Carlo sensitivity analysis was used to assess the impact of uncertainty in input
      parameters. A policy of annual testing and culling of all seropositive cattle in
      the population reduced the seroprevalence effectively and rapidly from 12% to <1%
      in the first year of simulation. The control strategies with discontinued
      breeding with offspring from all seropositive cows, chemotherapy of calves and
      vaccination of all cattle reduced the prevalence more slowly than culling but
      were still very effective (reduction of prevalence below 2% within 11, 23 and 3
      years of simulation, respectively). However, sensitivity analyses revealed that
      the effectiveness of these strategies depended strongly on the quality of the
      input parameters used, such as the horizontal and vertical transmission factors,
      the sensitivity of the diagnostic test and the efficacy of medication and
      vaccination. Finally, all models confirmed that it was not possible to completely
      eradicate N. caninum as long as the horizontal transmission process was not
      interrupted.

PMID- 16962191
TI  - The child health/family income gradient: Evidence from England.
AB  - Recent studies using Canadian and US data have documented a positive relationship
      between family income and child health, with the slope of the gradient being
      larger for older than younger children [Case, A., Lubotsky, D., Paxson, C., 2002.
      Economic status and health in childhood: the origins of the gradient. American
      Economic Review 92, 1308-1334; Currie, J., Stabile, M., 2003. Socioeconomic
      status and child health: why is the relationship stronger for older children?
      American Economic Review 93, 1813-1823]. In this paper we explore whether or not
      these findings hold for England, analysing a sample of over 13,000 children (and
      their parents) drawn from the Health Survey for England. While we find consistent
      and robust evidence of a significant family income gradient in child health,
      using the subjective general health status measure, the slope of the gradient is
      very small. Moreover, we find no evidence that the slope of the gradient
      increases with child age. Furthermore, we find no evidence of such a gradient
      with more objective measures, based on nurse examinations and blood test results.
      Together these results suggest that family income is not a major determinant of
      child health in England. Finally, we provide some evidence that nutrition and
      family lifestyle choices have an important role in determining child health and
      that child health is highly correlated within the family.

PMID- 16962192
TI  - Working memory related gamma oscillations in schizophrenia patients.
AB  - Recent reports show that the capability of neural networks supporting high
      frequency synchronization is reduced in the brain of schizophrenia patients.
      Specifically, deficits in gamma activity have been shown in schizophrenia
      patients during perception and simple cognitive tasks. However little is known
      about alterations in gamma responses during complex and higher cognitive
      processing. The main objective of this study was to investigate modulation of
      event-related gamma responses in tasks varying working memory (WM) load in
      schizophrenia patients (N=10) and healthy controls (N=10). Gamma amplitude values
      were obtained for a simple choice reaction task, a low WM demand task, and a high
      WM demand task. During all three tasks schizophrenia patients showed
      significantly slower reaction times and higher error rates than controls. A
      gradual increase of gamma amplitudes after stimulus onset was associated with
      increase of WM load in controls. In contrast, high amplitude gamma oscillations
      remained constant regardless of task difficulty in patients. These results
      suggest that healthy subjects used various cognitive strategies depending on task
      difficulty, while schizophrenia patients needed to initiate complex cognitive
      processes similar to those used during processing of novel contexts or stimuli
      even for the simple choice reaction task with low cognitive demand.

PMID- 16962193
TI  - Effects on c-Fos expression in the PAG and thalamus by selective input via
      tetrodotoxin-resistant afferent fibres from muscle and skin.
AB  - Nociceptive information from skin and muscle is differently processed at many
      levels of the central nervous system. However, with regard to nociceptive input
      from muscle to the thalamus, only few data are available. Here, we investigated
      the c-Fos expression in the thalamus and the periaqueductal grey matter (PAG)
      induced by electrical stimulation of tetrodotoxin-resistant (TTX-r), presumably
      nociceptive, afferent fibres. In addition, a comparison between the effects of
      TTX-r input from muscle and skin was made. In anaesthetised rats, a skin or a
      muscle nerve was stimulated electrically for 1h at an intensity supramaximal for
      unmyelinated fibres. To block TTX-sensitive afferents, TTX was applied to the
      sciatic nerve. c-Fos was visualized using DAB immunohistochemistry. Here we
      report for the first time that in the PAG and medial thalamus, the main effect of
      TTX-r input from muscle was a reduction in c-Fos expression, and that in some
      thalamic nuclei (e.g. posterior, reuniens, and central medial nuclei),
      significant differences in the number of c-Fos-positive cells were found after
      muscle and cutaneous input, respectively. The thalamic regions with the strongest
      effects of muscle input were the VL bilaterally and the VPL contralaterally
      (increase in c-Fos expression) as well as the rhomboid nucleus (decrease in c-Fos
      expression).

PMID- 16962194
TI  - Influence of harvest date and geographical location on kernel symptoms, fungal
      infestation and embryo viability of malting barley.
AB  - This study focused on the influence of harvest timing and geographical location
      on spring malting barley (potential malting variety) in terms of fungal
      infestation and seedling viability in symptomatic and asymptomatic kernels. The
      study was conducted over two consecutive crop years (2003-2004) at four locations
      in Slovakia. The following categories of the barley kernels were used for the
      assessment: kernels with black point symptoms (BPK), kernels with black cover on
      their surface (BCK), pink-colored kernels (PCK) and asymptomatic kernels (AK).
      The occurrence of various fungi was detected in all kernel categories ranging
      from 60 to 100%. The most frequent fungal contaminants were members of the genus
      Alternaria, recovered from BPK in the range of 52.6-69.85%, BCK (62.36-73.28%)
      and AK (55.35-69.58%). The prevalence of Alternaria spp. was recorded for each
      harvest time. Other dematiaceous fungi, Epicoccum nigrum and Cochliobolus sativus
      were found with medium frequency in the same three categories. However, C.
      sativus was recovered with a higher frequency in BPK (2.6-25.3%). In PCK, the
      most commonly recovered fungi were species of Fusarium with F. avenaceum (59.2
      93.2%) as the most prevalent. The infestation of kernels by fungi from other
      genera showed only low frequency within all the kernel categories investigated.
      There was no significant influence of the year and location on the proportion of
      the symptomatic kernel categories. Kernel germination was inhibited to a greater
      degree in the wetter and colder year. The strongest inhibition of germination
      ranging from 2.35 to 22.45% was recorded in PCK in all locations and both years.
      Germination declined from PCK to BCK (43.2-90.32%), and BPK (45.6-91.61%), while
      it was highest in AK at all harvest times (63-93.6%). This study found that the
      black covering symptoms (BCK) caused greater damage to viability of the kernels
      than black point symptoms (BPK). The delayed harvest time resulted not only in
      increasing numbers of discolored kernels and undesirable symptomatic kernel
      fractions but also in lower germination of the kernels tested.

PMID- 16962195
TI  - Use of whey protein beads as a new carrier system for recombinant yeasts in human
      digestive tract.
AB  - A new immobilizing protocol using whey protein isolates was developed to entrap
      recombinant Saccharomyces cerevisiae. The model yeast strain expresses the
      heterologous P45073A1 that converts trans-cinnamic acid into p-coumaric acid.
      Beads resulted from a cold-induced gelation of a whey protein solution (10%)
      containing yeasts (7.5 x 10(7)cells ml(-1)) into 0.1M CaCl(2). The viability and
      growth capability of yeasts were not altered by our entrapment process. The
      release and activity of immobilized yeasts were studied in simulated human
      gastric conditions. During the first 60 min of digestion, 2.2+/-0.9% (n=3) of
      initial entrapped yeasts were recovered in the gastric medium suggesting that
      beads should cross the gastric barrier in human. The P45073A1 activity of
      entrapped yeasts remained significantly higher (p<0.05) than that of free ones
      throughout digestion (trans-cinnamic acid conversion rate of 63.4+/-1.6% versus
      51.5+/-1.8% (n=3) at 120 min). The protein matrix seemed to create a
      microenvironment favoring the activity of yeasts in the stringent gastric
      conditions. These results open up new opportunities for the development of drug
      delivery system using recombinant yeasts entrapped in whey protein beads. The
      main potential medical applications include biodetoxication or the correction of
      digestive enzyme deficiencies.

PMID- 16962196
TI  - Slow release of molecules in self-assembling peptide nanofiber scaffold.
AB  - Biological hydrogels consisting of self-assembling peptide nanofibers are
      potentially excellent materials for various controlled molecular release
      applications. The individual nanofiber consists of ionic self-complementary
      peptides with 16 amino acids (RADA16, Ac-RADARADARADARADA-CONH(2)) that are
      characterized by a stable beta-sheet structure and undergo self-assembly into
      hydrogels containing approximately 99.5% w/v water. We report here on the
      diffusion properties of phenol red, bromophenol blue, 8-hydroxypyrene-1,3,6
      trisulfonic acid trisodium salt (pyranine, 3-PSA), 1,3,6,8-pyrenetetrasulfonic
      acid tetrasodium salt (4-PSA), and Coomassie Brilliant Blue G-250 (CBBG) through
      RADA16 hydrogels. The apparent diffusivity (D ) of phenol red (1.05+/-0.08 x 10(
      10) m(2) s(-1)) is higher than that of 3-PSA (0.050+/-0.004 x 10(-10) m(2) s(-1))
      and 4-PSA (0.007+/-0.002 x 10(-10) m(2) s(-1)). The difference in 3-PSA and 4-PSA
      diffusivities suggests that the sulfonic acid groups directly facilitate
      electrostatic interactions with the RADA16 fiber surface. Bromophenol blue and
      CBBG were not released from the hydrogel, suggesting that they interact strongly
      with the peptide hydrogel scaffold. The diffusivities (D ) of the dyes decreased
      with increasing hydrogel peptide concentration, providing an alternate route of
      controlling release kinetics. These results indicate that release profiles can be
      tailored through controlling nanofiber-diffusant molecular level interactions.

PMID- 16962197
TI  - Hypoxia-inducible gene expression system using the erythropoietin enhancer and 3'
      untranslated region for the VEGF gene therapy.
AB  - Gene therapy with the vascular endothelial growth factor (VEGF) gene is a
      potential treatment for many disorders or injuries with ischemia. However,
      unregulated expression of VEGF may induce pathological angiogenesis, promoting
      tumor growth, diabetic proliferative retinopathy and rupture of atherosclerotic
      plaque. Therefore, the effective regulation of the gene expression is one of the
      requirements for the VEGF gene therapy. In this research, we evaluated the
      hypoxia-inducible gene expression system with the erythropoietin (Epo) enhancer
      and the Epo 3'-untranslated region (UTR). The luciferase plasmids were
      constructed with the Epo enhancer (pEpo-SV-Luc), the Epo 3'-UTR (pSV-Luc-EpoUTR)
      or both (pEpo-SV-Luc-EpoUTR). The polyethylenimine/plasmid complexes were
      transfected to 293 or A7R5 cells and the cells were incubated under normoxia or
      hypoxia. The results showed that the Epo enhancer or Epo 3'-UTR increased the
      target gene expression under hypoxia. pEpo-SV-Luc-EpoUTR showed the highest
      luciferase expression. The VEGF expression plasmid with the Epo enhancer and 3'
      UTR was also constructed. The VEGF expression by pEpo-SV-VEGF-EpoUTR showed the
      highest specificity of the gene expression in the hypoxic cells. The results
      suggest that the VEGF plasmid with the Epo enhancer and the Epo 3'-UTR may be
      useful for gene therapy for ischemic diseases.

PMID- 16962198
TI  - Polyacetal and poly(ortho ester)-poly(ethylene glycol) graft copolymer
      thermogels: preparation, hydrolysis and FITC-BSA release studies.
AB  - Graft copolymers comprised of a polyacetal backbone with pendant poly(ethylene
      glycol) side-chains were prepared using a condensation reaction between a divinyl
      ethers, a diol and Fmoc-protected serinol, followed by deprotecting the amine and
      reacting the polyacetal with pendant amino groups with PEG-alpha-methoxy-omega
      succimidylcarbonate. A series of materials having lower critical solution
      temperature (LCST) between 25 and 60 degrees C has been prepared. Since LCST is
      determined by the hydrophilic-hydrophobic balance, and this in turn is determined
      by the molecular weight of the polyacetal backbone, the molecular weight of the
      grafted PEG and the amount grafted, materials having a desired LCST could be
      readily prepared. Incorporating FITC-BSA at 1 wt.% into the thermogel resulted in
      sustained release over about 100 days at pH 7.4 and 40 days at pH 5.5 without a
      burst and by reasonably linear kinetics. Incorporating FITC-BSA at 5 wt.% into
      the thermogel significantly increased delivery time at pH 5.5 and decreased the
      difference in delivery rates between pH 5.5 and pH 7.4. FITC-BSA is released by a
      predominantly erosion-controlled process and FITC-BSA depletion coincides closely
      with total gel dissolution. More rapidly eroding thermogels were prepared by
      replacing the polyacetal backbone with a poly(ortho ester) backbone. Such gels
      completely dissolved between 3 and 6 days. It is hoped that intermediate erosion
      rates can be achieved by preparing backbones containing both acetal and ortho
      ester linkages. Such materials have been prepared and shown to have LCST values
      in the desired range, but no erosion, or drug release studies have as yet been
      completed.

PMID- 16962199
TI  - A gas forming renal abscess in a person with diabetes mellitus and adult
      polycystic kidney disease.

PMID- 16962201
TI  - Optimization of the Monte Carlo code for modeling of photon migration in tissue.
AB  - The Monte Carlo method is frequently used to simulate light transport in turbid
      media because of its simplicity and flexibility, allowing to analyze complicated
      geometrical structures. Monte Carlo simulations are, however, time consuming
      because of the necessity to track the paths of individual photons. The time
      consuming computation is mainly associated with the calculation of the
      logarithmic and trigonometric functions as well as the generation of pseudo
      random numbers. In this paper, the Monte Carlo algorithm was developed and
      optimized, by approximation of the logarithmic and trigonometric functions. The
      approximations were based on polynomial and rational functions, and the errors of
      these approximations are less than 1% of the values of the original functions.
      The proposed algorithm was verified by simulations of the time-resolved
      reflectance at several source-detector separations. The results of the
      calculation using the approximated algorithm were compared with those of the
      Monte Carlo simulations obtained with an exact computation of the logarithm and
      trigonometric functions as well as with the solution of the diffusion equation.
      The errors of the moments of the simulated distributions of times of flight of
      photons (total number of photons, mean time of flight and variance) are less than
      2% for a range of optical properties, typical of living tissues. The proposed
      approximated algorithm allows to speed up the Monte Carlo simulations by a factor
      of 4. The developed code can be used on parallel machines, allowing for further
      acceleration.

PMID- 16962202
TI  - Feedback linearization based computer controlled medication design for automatic
      treatment of parturient paresis of cows.
AB  - Based on an existing model for calcium homeostatis (dynamics) and taking the help
      of feedback linearization philosophy of nonlinear control theory, two control
      design (medication) strategies are presented for automatic treatment of
      parturient paresis (milk fever) disease of cows. An important advantage of the
      new approach is that it results in a simple and straightforward method and
      eliminates the necessity of a significantly more complex neural network based
      nonlinear optimal control technique, as proposed by the author earlier. As an
      added advantage, unlike the neural network technique, the new approach leads to
      'closed form solution' for the nonlinear controller. Moreover, global asymptotic
      stability of the closed loop system is always guaranteed. Besides theoretical
      justifications, the resulting controllers (medication strategies) are validated
      from numerical simulation studies of the nonlinear system as well. Moreover, from
      a numerical study about the robustness of the algorithms with respect to
      parametric uncertainty, it was observed that the optimal control formulation is a
      better option over the dynamic inversion formulation.

PMID- 16962203
TI  - A new strategy for urinary sediment segmentation based on wavelet, morphology and
      combination method.
AB  - This paper presents a strategy for segmenting urinary sediment based on wavelet,
      morphology and combination method. Firstly, the wavelet transforms and morphology
      are used to get rid of the effect of the defocusing and get the subimages that
      include the particles. Then based on the characteristics of the subimages, edge
      detection and adaptive thresholding are employed adaptively. Finally, a
      simplified watershed algorithm for the overlapping particles is used. The
      experiment results show that the method can segment the defocusing urinary
      sediment images effectively and precisely.

PMID- 16962204
TI  - Genetic monitoring as a promising tool for conservation and management.
AB  - In response to ever-increasing anthropogenic changes to natural ecosystems,
      regional, national and international organizations have established guidelines
      for monitoring biological diversity. Most monitoring programs, however, do not
      take full advantage of the potential afforded by molecular genetic markers, which
      can provide information relevant to both ecological and evolutionary time frames,
      while costing less and being more sensitive and reliable than traditional
      monitoring approaches. As several molecular and computational approaches are
      relatively new, many technical and theoretical issues remain to be resolved.
      Here, we illustrate how DNA and population genetic data can provide valuable
      information, often unattainable via other approaches, for monitoring species of
      management, conservation and ecological interest.

PMID- 16962206
TI  - Simulation and analysis of solute transport in 2D fracture/pipe networks: the
      SOLFRAC program.
AB  - The Time Domain Random Walk (TDRW) method has been recently developed by Delay
      and Bodin [Delay, F. and Bodin, J., 2001. Time domain random walk method to
      simulate transport by advection-dispersion and matrix diffusion in fracture
      networks. Geophys. Res. Lett., 28(21): 4051-4054.] and Bodin et al. [Bodin, J.,
      Porel, G. and Delay, F., 2003c. Simulation of solute transport in discrete
      fracture networks using the time domain random walk method. Earth Planet. Sci.
      Lett., 6566: 1-8.] for simulating solute transport in discrete fracture networks.
      It is assumed that the fracture network can reasonably be represented by a
      network of interconnected one-dimensional pipes (i.e. flow channels). Processes
      accounted for are: (1) advection and hydrodynamic dispersion in the channels, (2)
      matrix diffusion, (3) diffusion into stagnant zones within the fracture planes,
      (4) sorption reactions onto the fracture walls and in the matrix, (5) linear
      decay, and (6) mass sharing at fracture intersections. The TDRW method is handy
      and very efficient in terms of computation costs since it allows for the one-step
      calculation of the particle residence time in each bond of the network. This
      method has been programmed in C++, and efforts have been made to develop an
      efficient and user-friendly software, called SOLFRAC. This program is freely
      downloadable at the URL (labo.univ
      poitiers.fr/hydrasa/intranet/telechargement.htm). It calculates solute transport
      into 2D pipe networks, while considering different types of injections and
      different concepts of local dispersion within each flow channel. Post-simulation
      analyses are also available, such as the mean velocity or the macroscopic
      dispersion at the scale of the entire network. The program may be used to
      evaluate how a given transport mechanism influences the macroscopic transport
      behaviour of fracture networks. It may also be used, as is the case, e.g., with
      analytical solutions, to interpret laboratory or field tracer test experiments
      performed in single fractures.

PMID- 16962207
TI  - Measuring behavioural susceptibility to obesity: validation of the child eating
      behaviour questionnaire.
AB  - The Child Eating Behaviour Questionnaire (CEBQ; [Wardle, J., Guthrie, C.A.,
      Sanderson, S., & Rapoport, L. (2001). Development of the children's eating
      behaviour questionnaire. Journal of Child Psychology and Psychiatry, 42, 963
      970]) is a parent-report questionnaire designed to assess eating styles related
      to obesity risk. It has been shown to have a robust factor structure and good
      internal reliability, but has not been validated against behavioural measures of
      eating. In the present study, associations were examined between three CEBQ
      scales (Satiety Responsiveness, SR; Food Responsiveness, FR; Enjoyment of Food,
      EF) and four aspects of eating behaviour (eating without hunger, caloric
      compensation, eating rate and energy intake at a meal) aggregated across up to
      five occasions, in a sample of 4-5-year olds. In multiple regression, the
      aggregated behavioural measures of eating explained 56% of the variance in SR,
      33% of the variance in FR and 40% of the variance in EF. These findings support
      the validity of the CEBQ as a parent-report instrument to assess 'obesogenic'
      eating behaviours in children. An easily-administered measure such as the CEBQ
      will be valuable in gathering data on the scale required to study the behavioural
      phenotype associated with obesity risk.

PMID- 16962208
TI  - An apple a day keeps the doctor away: children's evaluative categories of food.
AB  - This study explores how children evaluatively categorize foods based on their
      nutritional value. Three-year-olds, four-year-olds, seven-year-olds, and adults
      completed a task in which they categorized a list of 70 foods as healthy or
      junky. The results showed important developmental differences in participants'
      ability to accurately classify foods as healthy/junky and to provide relevant
      justifications for these classifications. These results suggest that a large
      amount of category learning occurs with development, especially as children
      incorporate different types of information about food nutrition into their
      evaluative category representations.

PMID- 16962209
TI  - Dose-dependent effects of peptide YY(3-36) on conditioned taste aversion in rats.
AB  - We used a conditioned taste aversion test to assess whether PYY(3-36) reduces
      food intake by producing malaise. Two-hour IV infusion of PYY(3-36) (8, 15, and
      30 pmol/kg/min) at dark onset in non-food-deprived rats produced a dose-dependent
      inhibition of feeding and a conditioned aversion to the flavored chow paired with
      PYY(3-36) infusion. In food-deprived rats, PYY(3-36) at 2 and 4 pmol/kg/min
      inhibited intake of a flavored saccharin solution without producing conditioned
      taste aversion, whereas higher doses (8 and 15 pmol/kg/min) inhibited saccharin
      intake and produced taste aversion. These results suggest that anorexic doses of
      PYY(3-36) may produce a dose-dependent malaise in rats, which is similar to that
      reported for PYY(3-36) infusion in humans. Previous studies have shown that PYY(3
      36) potently inhibits gastric emptying, and that gut distention can produce a
      conditioned taste aversion. Thus, PYY(3-36) may produce conditioned taste
      aversion in part by slowing gastric emptying.

PMID- 16962210
TI  - Involvement of G-protein betagamma subunits on the influence of inhibitory alpha2
      autoreceptors on the angiotensin AT1-receptor modulation of noradrenaline release
      in the rat vas deferens.
AB  - The influence of alpha2-autoreceptors on the facilitation of [3H]-noradrenaline
      release mediated by angiotensin II was studied in prostatic portions of rat vas
      deferens preincubated with [3H]-noradrenaline. Angiotensin II enhanced tritium
      overflow evoked by trains of 100 pulses at 8 Hz, an effect that was attenuated by
      the AT1-receptor antagonist losartan (0.3-1 microM), at concentrations suggesting
      the involvement of the AT1B subtype. The effect of angiotensin II was also
      attenuated by inhibition of phospholipase C (PLC) and protein kinase C (PKC)
      indicating that prejunctional AT1-receptors are coupled to the PLC-PKC pathway.
      Angiotensin II (0.3-100 nM) enhanced tritium overflow more markedly, up to 64%,
      under conditions that favor alpha2-autoinhibition, observed when stimulation
      consisted of 100 pulses at 8 Hz, than under poor alpha2-autoinhibition
      conditions, only up to 14%, observed when alpha2-adrenoceptors were blocked with
      yohimbine (1 microM) or when stimulation consisted of 20 pulses at 50 Hz.
      Activation of PKC with 12-myristate 13-acetate (PMA, 0.1-3 microM) also enhanced
      tritium overflow more markedly under strong alpha2-autoinhibition conditions.
      Inhibition of Gi/o-proteins with pertussis toxin (8 microg/ml) or blockade of
      Gbetagamma subunits with the anti-betagamma peptide MPS-Phos (30 microM)
      attenuated the effects of angiotensin II and PMA. The results indicate that
      activation of AT1-receptors coupled to the PLC-PKC pathway enhances noradrenaline
      release, an effect that is markedly favoured by an ongoing activation of alpha2
      autoreceptors. Interaction between alpha2-adrenoceptors and AT1-receptors seems
      to involve the betagamma subunits released from the Gi/o-proteins coupled to
      alpha2-adrenoceptors and protein kinase C activated by AT1-receptors.

PMID- 16962211
TI  - Emergence of a spermine-sensitive, non-inactivating conductance in mature
      hippocampal CA1 pyramidal neurons upon reduction of extracellular Ca2+:
      dependence on intracellular Mg2+ and ATP.
AB  - Large and protracted elevations of intracellular [Ca(2+)] and [Na(+)] play a
      crucial role in neuronal injury in ischemic conditions. In addition to excessive
      glutamate receptor activation, other ion channels may contribute to disruption of
      intracellular ionic homeostasis. During episodes of ischemia, extracellular
      [Ca(2+)] falls significantly. Here we report the emergence of an inward current
      in hippocampal CA1 pyramidal neurons in acute brain slices from adult mice upon
      reduction/removal of [Ca(2+)](e). The magnitude of the current was 100-300pA at 
      65mV holding potential, depending on intracellular constituents. The current was
      accompanied by intense neuronal discharge, observed in both whole-cell and cell
      attached patch configurations. Sustained currents and increased neuronal firing
      rates were both reversed by restoration of physiological levels of [Ca(2+)](e),
      or by application of spermine (1mM). The amplitudes of the sustained currents
      were strongly reduced by raising intracellular [Mg(2+)], but not by extracellular
      [Mg(2+)] increases. Elevated intracellular ATP also reduced the current. This
      conductance is similar in several respects to the "calcium-sensing, non-selective
      cation current" (csNSC), previously described in cultured mouse hippocampal
      neurons of embryonic origin. The dependence on intracellular [ATP] and [Mg(2+)]
      shown here, suggests a possible role for this current in disruption of ionic
      homeostasis during metabolic stress that accompanies excessive neuronal
      stimulation.

PMID- 16962212
TI  - Cognitive impairment and frontal-subcortical geriatric syndrome are associated
      with metabolic syndrome in a stroke-free population.
AB  - BACKGROUND: Metabolic syndrome (Met.S) consists of a conglomeration of obesity,
      hypertension, glucose intolerance, and dislipidemia. Frontal-subcortical
      geriatric syndrome (FSCS) is caused by ischemic disruption of the frontal
      subcortical network. It is unknown if Met.S is associated with FSCS. METHODS: We
      evaluated 422 community-dwelling elderly (> or =60) in Brazil. FSCS was defined
      as the presence of at least one frontal release sign (grasping, palmomental,
      snout, or glabellar) plus coexistence of > or =3 the following criteria: (1)
      cognitive impairment, (2) late-onset depression, (3) neuromotor dysfunction, and
      (4) urgency incontinence. All values were adjusted to age and gender. RESULTS:
      Met.S was present in 39.3% of all subjects. Cases without any of the FSCS
      components represented 37.2% ('successful neuroaging' group). People with 1-3 of
      the FSCS components ('borderline pathological neuroaging' group) were majority
      (52.6%), whereas those with 4-5 of these components (FSCS group) were minority
      (10.2%). Met.S was significantly associated with FSCS (OR=5.9; CI: 1.5-23.4) and
      cognitive impairment (OR=2.2; CI: 1.1-4.6) among stroke-free subjects. Number of
      Met.S components explained 30.7% of the variance on the number of FSCS criteria
      (P<0.001). If Met.S were theoretically removed from this population, prevalence
      of FSCS would decline by 31.6% and that of cognitive impairment by 21.4%.
      CONCLUSIONS: Met.S was significantly associated with a 5.9 and 2.2 times higher
      chance of FSCS and cognitive impairment, respectively. Met.S might be a major
      determinant of 'successful' or 'pathological' neuroaging in western societies.

PMID- 16962213
TI  - Heterogeneity of mild cognitive impairment and other predementia syndromes in
      progression to dementia.
AB  - Mild cognitive impairment (MCI) is thought to be a prodromal phase of Alzheimer's
      disease, but in population-based studies MCI classification is less consistent
      than in clinical series, suggesting that MCI is a heterogeneous descriptor and
      the outcome at follow-up depends on which population is studied and how MCI is
      defined. We discussed in the present paper the issue of the heterogeneity of MCI
      and other predementia syndromes, both in clinical presentation and progression to
      dementia, supported by the findings of the Italian Longitudinal Study on Aging
      (ILSA) and other population-based and clinical-based studies.

PMID- 16962214
TI  - Frontal connections and cognitive changes in normal aging rhesus monkeys: a DTI
      study.
AB  - Recent anatomical studies have found that cortical neurons are mainly preserved
      during the aging process while myelin damage and even axonal loss is prominent
      throughout the forebrain. We used diffusion tensor imaging (DT-MRI) to evaluate
      the hypothesis that during the process of normal aging, white matter changes
      preferentially affect the integrity of long corticocortical association fiber
      tracts, specifically the superior longitudinal fasciculus II and the cingulum
      bundle. This would disrupt communication between the frontal lobes and other
      forebrain regions leading to cognitive impairments. We analyzed DT-MRI datasets
      from seven young and seven elderly behaviorally characterized rhesus monkeys,
      creating fractional anisotropy (FA) maps of the brain. Significant age-related
      reductions in mean FA values were found for the superior longitudinal fasciculus
      II and the cingulum bundle, as well as the anterior corpus callosum. Comparison
      of these FA reductions with behavioral measures demonstrated a statistically
      significant linear relationship between regional FA and performance on a test of
      executive function. These findings support the hypothesis that alterations to the
      integrity of these long association pathways connecting the frontal lobe with
      other forebrain regions contribute to cognitive impairments in normal aging. To
      our knowledge this is the first investigation reporting such alterations in the
      aging monkey.

PMID- 16962216
TI  - Palmar shelf arthroplasty in the rheumatoid wrist revisited.

PMID- 16962215
TI  - Autologous neu DNA vaccine can be as effective as xenogenic neu DNA vaccine by
      altering administration route.
AB  - We examined the therapeutic efficacy of xenogenic human N'-terminal neu DNA
      vaccine and autologous mouse N'-terminal neu DNA vaccine on MBT-2 tumor cells in
      C3H mice. Intramuscular injection of xenogenic and autologous neu DNA vaccines
      produced comparable therapeutic efficacies. Mouse and human N'-neu DNA vaccine
      induced tumor infiltration of CD8(+) T cells, while the human vaccine was less
      effective at stimulating natural killer cells. Depletion of CD8(+) T cells
      abolished the therapeutic efficacy of both types of DNA vaccines. On the other
      hand, xenogenic neu DNA vaccine showed significantly better therapeutic efficacy
      than autologous DNA vaccine with gene gun immunization. Increased infiltration of
      CD8(+) T cells was correlated with enhanced therapeutic efficacy in the human N'
      neu group of mice. Therefore, intramuscular injection can enhance the therapeutic
      efficacy of autologous neu DNA vaccine.

PMID- 16962217
TI  - Posterior interosseous nerve palsy caused by osteoarthritic synovitis of the
      proximal radioulnar joint.

PMID- 16962218
TI  - Information seeking during "bad news" oncology interactions: Question asking by
      patients and their companions.
AB  - Previous research has investigated patient question asking in clinical settings
      as a strategy of information seeking and as an indicator of the level of active
      patient participation in the interaction. This study investigates questions asked
      by patients and their companions during stressful encounters in the oncology
      setting in the USA. We transcribed all questions patients and companions asked
      the oncologist during 28 outpatient interactions in which "bad news" was
      discussed (n = 705) and analyzed them for frequency and topic. Additionally, we
      analyzed the extent to which personal and demographic characteristics and
      independently obtained ratings of the oncologist-patient/companion relationships
      were related to question asking. Findings demonstrated that at least one
      companion was present in 24 (86%) of the 28 interactions and companions asked
      significantly more questions than patients. The most frequently occurring topics
      for both patients and companions were treatment, diagnostic testing, diagnosis,
      and prognosis. In general, personal and demographic characteristics were
      unrelated to question asking, but older patients asked fewer questions, while
      more educated patients asked more questions. With regard to ratings of the
      quality of the dyadic relationships, results showed that "trust" between the
      physician and companions was positively correlated and "conversational dominance
      by physician" was negatively correlated with the frequency of companion
      questions. Additionally, positive ratings of the relationship between physicians
      and companions were correlated with fewer patient questions. This study
      demonstrates that companions are active participants in stressful oncology
      interactions. Future research and physician training in communication would
      benefit from expanding the focus beyond the patient-physician dyad to the roles
      and influence of multiple participants in medical interactions.

PMID- 16962219
TI  - Socioeconomic position in childhood and in adulthood and functional limitations
      in midlife: Data from a nationally-representative survey of French men and women.
AB  - Research shows that lifetime socioeconomic circumstances are associated with
      adult health. Yet most studies to date have focused on mortality and additional
      data on morbidity outcomes are needed. Additionally, most research in this area
      has been conducted in Northern European countries or in the United States, and
      less is known about the extent of socioeconomic inequalities in health in other
      industrialized countries with different health and labour market characteristics.
      In this study, we examined the relationship between the socioeconomic trajectory
      from childhood to adulthood and functional limitations in midlife in France. We
      used data from a nationally-representative sample of French men and women
      conducted in 2002-2003 (the Life History survey). Participants (n = 4798) were 35
      64 years of age at the time of the survey. standardized morbidity ratios (SMRs)
      associated with different lifelong trajectories were estimated using indirect age
      standardization. Overall, the socioeconomic trajectory from childhood to
      adulthood was associated with functional limitations in midlife in both men and
      women. The experience of lifelong socioeconomic disadvantage was associated with
      SMRs of 1.44, p < 0.0001 in men and 1.21, p = 0.0207 in women. In men, the
      prevalence of functional limitations was low among those who experienced upward
      intergenerational mobility and high among those who experienced a downward
      trajectory during the course of their professional career. Additionally, the
      prevalence of functional limitations was elevated among men and women who
      experienced unemployment. These findings indicate that in French men and women,
      lifetime socioeconomic circumstances are associated with functional limitations
      in midlife. Understanding the mechanisms that underlie these health disparities
      will require additional studies of specific health outcomes.

PMID- 16962220
TI  - Barriers to condom purchasing: Effects of product positioning on reactions to
      condoms.
AB  - Correct and consistent condom use has been promoted as a method to prevent
      sexually transmitted infections including HIV. Yet research has repeatedly shown
      that people fail to use condoms consistently. One influence on the pervasive lack
      of condom use that has received relatively little attention is the context in
      which consumers are exposed to condoms (i.e., how condoms are displayed in retail
      settings). In this paper we present two studies explored variations in condom
      shelf placement and its effects on people's condom attitudes and acquisition.
      Study 1 explored the shelf placement of condoms in 59 retail outlets in
      Connecticut, USA and found that condoms were typically located in areas of high
      visibility (e.g., next to the pharmacy counter) and on shelves adjacent to
      feminine hygiene and disease treatment products. In Study 2, 120 heterosexual
      undergraduate students at the University of Connecticut were randomly assigned to
      evaluate condoms adjacent to sensual, positive, neutral, or negative products and
      found that overall men reported more positive attitudes and acquired more condoms
      when exposed to condoms in a sensual context compared to women in the same
      condition. Among women, condom attitudes were more positive in the context of
      neutral products; condom acquisition was strongest for women exposed to condoms
      in the positive aisles. These results suggest a gender-specific approach to
      condom promotion. Implications of these studies for HIV prevention, public
      health, and condom marketing strategies are discussed.

PMID- 16962221
TI  - Socioeconomic gradients in smoking among young women: A British survey.
AB  - Marked and increasing socioeconomic gradients in cigarette smoking are well
      established. Tracking these differentials among women requires appropriate
      measures of their socioeconomic position (SEP) which are equivalent across older
      and younger age groups. This study examines socioeconomic gradients in cigarette
      smoking by age among women aged 20-34, using a standard indicator of SEP (age
      left full-time education) and alternative indicators which take account of
      changes in women's educational levels across age cohorts. The study is based on a
      large cross-sectional British data set (n = 12,398), the Southampton Women's
      Survey, conducted 1998-2002. Poisson log-linear regression with adjusted variance
      was used to predict smoking status (ever smoked > or =1 cigarette a day for 1
      year, currently smoking > or =1 cigarette a day, and ex-smoker - ever-smoker not
      currently smoking > or =1 cigarette a day) in models which controlled for SEP,
      age and year of interview. Socioeconomic gradients in ever-smoking were marked
      but stable across age groups. With quitting more prevalent in the higher than
      lower socioeconomic groups, gradients in current smoking steepened across age
      groups, with significant age/SEP interactions. The socioeconomic patterning of
      ever, ex and current smoking was similar using both the standard and alternative
      measures of education, but interactions were less pronounced with the alternative
      measures. Socioeconomic indicators which take account of the recent and rapid
      increase in women's educational participation rates may provide a more reliable
      indication of age-related differentials in smoking status than standard measures.
      Nonetheless, both conventional and alternative measures point to stable
      socioeconomic differentials in rates of ever-smoking and widening differentials
      in current smoking across age groups. Our study confirms that addressing the link
      between socioeconomic disadvantage and tobacco use remains a major challenge for
      the tobacco control community.

PMID- 16962222
TI  - Rape perpetration by young, rural South African men: Prevalence, patterns and
      risk factors.
AB  - Sexual violence is a well-recognised global health problem, but there has been
      remarkably little research on men as perpetrators. The objectives of this paper
      are to describe the prevalence, patterns and factors associated with rape of an
      intimate partner and a woman who was not a partner with men aged 15-26 years in
      rural South Africa. The analysis presented here is of data collected during a
      baseline survey of participants in a cluster randomised controlled trial of an
      HIV behavioural intervention. A total of 1370 male volunteers were recruited from
      70 rural South African villages. They completed a questionnaire asking about
      background, sexual practices and perpetration of rape and intimate partner
      violence. Among these men 16.3% had raped a non-partner, or participated in a
      form of gang rape; 8.4% had been sexually violent towards an intimate partner;
      and 79.1% had done neither. The mean age of first rape was 17 years. There was
      overlap between rape of a non-partner and partner, in that 44.3% of men who raped
      an intimate partner had also raped a non-partner, but overall the great majority
      of men who raped did not disclose both types of rape. The factors associated with
      rape of an intimate partner and non-partner had similarities and differences.
      After adjusting for the other variables, both forms of rape were strongly
      associated with ever having been physically violent to a partner, having had
      transactional sex with a casual partner and more sexual partners. Non-partner
      rape was also associated with peer-related variables, including gang membership
      and peer pressure to have sex, and also drug use. Non-partner rape was more
      common among wealthier and relatively more socially advantaged men. Both types of
      rape were associated with having more adverse childhood experiences. There was
      considerable overlap between rape-associated factors and known HIV risk factors,
      suggesting a need for further research on the interface of rape and HIV, and
      integrated prevention programming.

PMID- 16962223
TI  - Action monitoring and perfectionism in anorexia nervosa.
AB  - To study action monitoring in anorexia nervosa, behavioral and EEG measures were
      obtained in underweight anorexia nervosa patients (n=17) and matched healthy
      controls (n=19) while performing a speeded choice-reaction task. Our main
      measures of interest were questionnaire outcomes, reaction times, error rates,
      and the error-related negativity ERP component. Questionnaire and behavioral
      results indicated increased perfectionism in patients with anorexia nervosa. In
      line with their perfectionism and controlled response style patients made
      significantly less errors than controls. However, when controlling for this
      difference in error rates, the EEG results demonstrated a reduced error-related
      negativity in the patient group. These seemingly contradictory outcomes of
      improved performance and reduced error monitoring are discussed in relation with
      indications of anterior cingulate cortex hypoactivity in anorexia nervosa
      patients.

PMID- 16962224
TI  - Quetiapine in combination with citalopram in patients with unipolar psychotic
      depression.
AB  - This 6-week, open-label, multicenter study evaluated the efficacy and safety of
      quetiapine in combination with citalopram in adult patients (n=25) with ICD
      10/DSM-IV unipolar psychotic depression. The primary endpoint was change from
      baseline to Week 6 in the Hamilton Depression Rating Scale (HAM-D-21) score.
      Secondary endpoints were change from baseline to Week 6 in the Brief Psychiatric
      Rating Scale (BPRS) and the Clinical Global Impression (CGI) Scale scores.
      Spontaneously reported adverse events (AEs), the Simpson Angus Scale (SAS), and
      the Udvalg for Kliniske Undersogelser (UKU) side effects rating scale scores were
      recorded. Patients' average age was 51.4 years and baseline weight was 72.6 kg.
      Quetiapine (50-750 mg/day, mean dose+/-SD: 303+/-118 mg/day), in combination with
      citalopram (20-60 mg/day, mean dose+/-SD: 34+/-12 mg/day), provided significant
      improvements in depression. Mean (+/- SD) HAM-D-21 was reduced to 13.25+/-10.87
      at Week 6 from a baseline value of 31.21+/-5.18. Significant improvement of
      psychotic symptoms (mean+/-SD) was indicated by the decrease from baseline
      (59.25+/-6.60) to Week 6 (35.25+/-15.60) in BPRS scores. No serious AEs occurred.
      The mean change in weight was +2.1 kg. Mean (+/- SD) weight at visit 1 was 72.72
      (+/-16.34) kg and mean (SD) weight at visit 4 was 74.79 (+/-18.69) kg. Quetiapine
      in combination with citalopram appears to be effective and is well tolerated in
      the treatment of unipolar psychotic depression. Further studies of larger, double
      blind, parallel-group design are warranted to confirm these findings.

PMID- 16962225
TI  - In vitro anti-microbial and in vivo cytokine modulating effects of different
      prepared Chinese herbal medicines.
AB  - The toxicity, antimicrobial and cytokine modulating effects of herbal medicines
      in treating periodontal diseases were evaluated in this study. Using the broth
      dilution method and disc agar diffusion test, in individual and combined decocted
      preparations, different concentrations of Ching-Wei-San and its individual herbal
      components, Coptidis rhizoma, Angelicae sinensis radix, Rehmanniae radixet
      rhizom, Moutan radicis cortex, and Cimicifuga foetida, were tested for in vitro
      inhibitory effects on three well-known plaque-causing bacteria, Porphyromonas
      gingivialis, Streptococcus sanguis, and Streptococcus mutans, and two common
      pathogens, Staphylococcus aureus and Escherichia coli. The cytokine modulating
      effects were evaluated in Balb/c mice. The results suggested that one milliliter
      Ching-Wei-San at the 25,000 mg/mL concentration daily for the mice had
      significantly high levels in the liver function indexes in the 3-day acute
      toxicity test and in both the liver and kidney function indexes in the 28-day
      subacute toxicity test (P<0.01). The 250 mg/mL Ching-Wei-San is comparable to 250
      mg/mL of tetracycline, and had similar inhibitory effects on the tested bacteria.
      Coptidis rhizoma (62.5 mg/mL) was the only individual herbal component to show
      100% inhibitory effects. The mean cytokine ratios of IL-2, IL-4, IFN-gamma, and
      TNF-alpha in Balb/c mice treated with individual herbal components were shown to
      be different from each other. Ching-Wei-San modulated the immunity of mice, up
      regulated IL-2, IL-4 and TNF-alpha, but down-regulated IFN-gamma. The effects of
      none of the individual herbal components alone can substitute for the cumulative
      effect of Ching-Wei-San.

PMID- 16962226
TI  - Restraint stress alters the duodenal expression of genes important for lipid
      metabolism in rat.
AB  - Stress, such as trauma and injury, is known to cause transcriptional changes in
      various tissues; however, there is little information on tissue-specific gene
      expression in response to stress. Here, we have examined duodenal gene expression
      in rats subjected to whole-body immobilization in order to elucidate the
      mechanism underlying the stress response in the duodenum--one of the tissues that
      is most sensitive to external stress. DNA microarray analysis revealed that the
      immobilization for 2 weeks caused great changes in gene expression in the rat
      duodenum: 165 genes exhibited more than a two-fold change in expression level
      (103 up-regulated; 62 down-regulated). In addition, functional classification of
      these genes showed that immobilization preferentially stimulated the expression
      of genes related to lipid metabolism, including genes encoding mitochondrial HMG
      CoA synthase, a key enzyme in ketogenesis; solute carrier 27A2, a fatty acid
      transporter; and dienoyl CoA reductase, a key enzyme in beta-oxidation. To
      elucidate the factors mediating these immobilization-induced changes, we treated
      rats and small intestinal IEC-6 cells with dexamethasone and hydrogen peroxide.
      In both rats and IEC-6 cells, treatment with dexamethasone induced changes in
      gene expression that mimicked the immobilization-mediated increase in expression
      of the mitochondrial HMG-CoA synthase and dienoyl CoA reductase transcripts,
      suggesting that stress-induced synthesis of glucocorticoid hormones mediates, at
      least in part, the stress response in the duodenum. These results suggest that
      immobilization may alter lipid metabolism in the small intestine by modifying the
      expression of specific genes through which the small intestine may seek to
      protect itself from stress-induced damage.

PMID- 16962227
TI  - Evaluation of monoquaternary pyridinium oximes potency to reactivate tabun
      inhibited human acetylcholinesterase.
AB  - Monoquaternary N-benzyl-4-hydroxyiminomethylpyridinium bromide (Py-4-H) and its
      analogous with diverse substituents introduced into the phenyl ring (Py-4-CH(3),
      Py-4-Br, Py-4-Cl and Py-4-NO(2)) were synthesized in order to examine their
      potency as reactivators of tabun-inhibited human erythrocyte acetylcholinesterase
      (AChE; EC 3.1.1.7). Within 24h, the reactivation of tabun-inhibited AChE reached
      80% with Py-4-CH(3), Py-4-Br and Py-4-Cl, 40% with Py-4-NO(2), and 30% with Py-4
      H. The overall reactivation rate constants were up to 5.0min(-1)M(-1). All oximes
      inhibited human AChE reversibly, and the inhibition potency increased in the
      following order Py-4-Br<Py-4-Cl<Py-4-CH(3)<Py-4-H<Py-4-NO(2). Although oximes Py
      4-H and Py-4-NO(2) did not show significant reactivation ability, these oximes
      might be of interest as pre-treatment drugs due to their high affinity for the
      native AChE. Docking studies were carried out to elucidate the differences in
      oximes potency. The orientations of all studied oximes in the active site of
      human AChE have been proposed by flexible ligand docking with AutoDock 3.0.
      Analyses of the obtained complexes revealed the presence of numerous hydrogen
      bonds and close contacts between the oximes and the residues in the active site.
      Final docked energies predicted correctly the relative order of the inhibition
      potency of compounds (except in the case of Py-4-CH(3)) as well as the most
      probable orientation of the best reactivator, Py-4-Br, which can result in an
      attack on the phosphorus atom of the tabun-phosphorylated human AChE.

PMID- 16962228
TI  - Comprehensive analysis of differential gene expression profiles on D
      galactosamine-induced acute mouse liver injury and regeneration.
AB  - Microarray analysis of RNA from d-galactosamine (GalN)-administered mouse livers
      was performed to establish a global gene expression profile during injury and
      regeneration stages at two different doses. A single dose of GalN at 266 or 26.6
      mg/kg body weight was given intraperitoneally, and the liver samples were
      obtained after 6, 24, and 72 h. Histopathologic studies enabled the
      classification of the D-galactosamine effect into injury (6, 24 h) and
      regeneration (72 h) stages. By using the Applied Biosystems mouse genome survey
      microarray, a total of 7267 out of 33,315 (21.8%) genes were found to be
      statistically reliable at p<0.05 by two-way ANOVA, and 1469 (4.4%) probes at
      false discovery rate <5% by significance analysis of microarray. Among the
      statistically reliable clones by both analytical methods, 389 genes were
      differentially expressed when compared with non-treated control, with more than a
      1.625-fold difference (which equals 0.7 in log(2) scale) at one or more GalN
      treatment conditions and with less than 1.625-fold difference at all three
      vehicle-treated conditions. Three hundred thirty six genes and 13 genes were
      identified as injury- and regeneration-specific genes, respectively, showing that
      most of the transcriptomic changes were seen during the injury stage.
      Furthermore, multiple genes involved in protein synthesis and degradation, mRNA
      processing and binding, and cell cycle regulation showed variable transcript
      levels upon acute GalN administration.

PMID- 16962229
TI  - The mysterious trace amines: protean neuromodulators of synaptic transmission in
      mammalian brain.
AB  - The trace amines are a structurally related group of amines and their isomers
      synthesized in mammalian brain and peripheral nervous tissues. They are closely
      associated metabolically with the dopamine, noradrenaline and serotonin
      neurotransmitter systems in mammalian brain. Like dopamine, noradrenaline and
      serotonin the trace amines have been implicated in a vast array of human
      disorders of affect and cognition. The trace amines are unique as they are
      present in trace concentrations, exhibit high rates of metabolism and are
      distributed heterogeneously in mammalian brain. While some are synthesized in
      their parent amine neurotransmitter systems, there is also evidence to suggest
      other trace amines may comprise their own independent neurotransmitter systems. A
      substantial body of evidence suggests that the trace amines may play very
      significant roles in the coordination of biogenic amine-based synaptic
      physiology. At high concentrations, they have well-characterized presynaptic
      "amphetamine-like" effects on catecholamine and indolamine release, reuptake and
      biosynthesis; at lower concentrations, they possess postsynaptic modulatory
      effects that potentiate the activity of other neurotransmitters, particularly
      dopamine and serotonin. The trace amines also possess electrophysiological
      effects that are in opposition to these neurotransmitters, indicating to some
      researchers the existence of receptors specific for the trace amines. While
      binding sites or receptors for a few of the trace amines have been advanced, the
      absence of cloned receptor protein has impeded significant development of their
      detailed mechanistic roles in the coordination of catecholamine and indolamine
      synaptic physiology. The recent discovery and characterization of a family of
      mammalian G protein-coupled receptors responsive to trace amines such as beta
      phenylethylamine, tyramine, and octopamine, including socially ingested
      psychotropic drugs such as amphetamine, 3,4-methylenedioxymethamphetamine, N,N
      dimethyltryptamine, and lysergic acid diethylamide, have revitalized the field of
      scientific studies investigating trace amine synaptic physiology, and its
      association with major human disorders of affect and cognition.

PMID- 16962230
TI  - Placenta increta: Use of dynamic MRI for diagnosis and evaluation of placental
      vascularity.

PMID- 16962231
TI  - Reducing topological defects in self-organizing maps using multiple scale
      neighborhood functions.
AB  - In this paper, we propose a method of reducing topological defects in self
      organizing maps (SOMs) using multiple scale neighborhood functions. The multiple
      scale neighborhood functions are inspired by multiple scale channels in the human
      visual system. To evaluate the proposed method, we applied it to the traveling
      salesman problem (TSP), and examined two indexes: the tour length of the solution
      and the number of kinks in the solution. Consequently, the two indexes are lower
      for the proposed method. These results indicate that our proposed method has the
      ability to reduce topological defects.

PMID- 16962232
TI  - Tumor of the conus medullaris treated with antituberculous therapy.
AB  - This case report concerns a 21-year-old man developing left leg paresis.
      Evaluation with magnetic resonance imaging (MRI) showed an intramedullary tumor
      in the conus region. He was planned for surgery but preoperative investigation
      indicated he had tuberculosis and the tumor was presumed to be a tuberculoma.
      Antituberculous therapy was started and the patient improved neurologically. The
      patient was followed clinically and with consecutive MRI during 2 years and the
      last MRI showed that the lesion had disappeared completely. Intramedullary
      tuberculomas are rare but important differential diagnosis in patients with
      spinal cord mass lesions. The role of medical and surgical treatment of
      intramedullary tuberculomas is discussed.

PMID- 16962233
TI  - Comparison of adsorption capacity of young brown coals and humic acids prepared
      from different coal mines in Anatolia.
AB  - Binding of Zn2+ and Cd2+ cations to relatively young brown coals YBC (lignite),
      humic acids (HAs) and commercial humic acid (CHA) were studied in aqueous media
      at pH 2.7-6 by polarographic method. This study was conducted to evaluate the
      removal of heavy metals in an aquatic system without prior treatment. The general
      principles of cation binding to YBC and humic materials are discussed. Sorption
      of heavy metal ions (Zn2+ and Cd2+) on samples of YBCs from three areas (Ilgin,
      Beysehir, and Ermenek) in the vicinity of the city of Konya in Anatolia (Turkey)
      were compared with sorption of these metal ions on HAs, prepared from these YBCs.
      The ability of both types of sorbent to remove metals from aqueous solutions was
      studied as a function of pH and concentration of initial metal solutions.
      Sorption depends strongly on pH, the origin of the YBC and on the nature of the
      metal ion. Whereas, for YBCs the main ligand groups seem to be carboxylate ions,
      this is not the case for the HA polymers, prepared from three YBCs, which differ
      substantially from properties of commercial samples of "HA". The process is very
      efficient especially in the case of low concentrations of pollutants in water,
      where common methods are either economically unfavorable or technically
      complicated. Of the two metal ions examined, Cd2+ was found to form the most
      stable HA complexes, followed by Zn. Effective removal of metals was demonstrated
      at pH-values of 5-5.7. The adsorption isotherm was measured at 25 degrees C,
      using adsorptive solutions at the optimum pH-value to determine the adsorption
      capacity. An important aspect of the proposed method was that the removal was
      performed on several metals at a pH-range in which a given metal undergoes an
      adsorption process making the method useful for wastewater treatment.

PMID- 16962234
TI  - Case study of the sonochemical decolouration of textile azo dye Reactive Black 5.
AB  - The decolouration and mineralization of reactive dye C.I. Reactive Black 5, a
      well-known representative of non-biodegradable azo dyes, by means of ultrasonic
      irradiation at 20, 279 and 817kHz has been investigated with emphasis on the
      effect of various parameters on decolouration and degradation efficiency.
      Characterization of the used ultrasound systems was performed using calorimetric
      measurements and oxidative species monitoring using Fricke and iodine dosimeter.
      Experiments were carried out with low frequency probe type, and a high-frequency
      plate type transducer at 50, 100 and 150W of acoustic power and within the 5
      300mg/L initial dye concentration range. Decolouration, as well as radical
      production, increased with increasing frequency, acoustic power, and irradiation
      time. Any increase in initial dye concentration results in decreased
      decolouration rates. Sonochemical decolouration was substantially depressed by
      the addition of 2-methyl-2-propanol as a radical scavenger, which suggests
      radical-induced reactions in the solution. Acute toxicity to marine bacteria
      Vibrio fischeri was tested before and after ultrasound irradiation. Under the
      conditions employed in this study, no toxic compounds were detected after 6h of
      irradiation. Mineralization of the dye was followed by TOC measurements.
      Relatively low degradation efficiency (50% after 6h of treatment) indicates that
      ultrasound is rather inefficient in overall degradation, when used alone.

PMID- 16962235
TI  - PANK2 gene analysis confirms genetic heterogeneity in neurodegeneration with
      brain iron accumulation (NBIA) but mutations are rare in other types of adult
      neurodegenerative disease.
AB  - Mutations in the pantothenate kinase 2 gene (PANK2) are the cause of pantothenate
      kinase associated neurodegeneration (PKAN), an autosomal recessive (AR) disorder
      characterized by motor symptoms as such as dystonia or parkinsonism, mental
      retardation, retinitis pigmentosa and iron accumulation in the brain. As many
      neurodegenerative conditions have similar clinical features we screened a number
      of adult and childhood onset movement disorders for PANK2 mutation. This included
      cases with neurodegeneration and brain iron accumulation, corticobasal
      degeneartion, progressive supranuclear palsy (PSP), Parkinson's disease (PD),
      multiple system atropy, giant axonal neuropathy (GAN), neuroaxonal dystrophy
      (NAD), Guam dementia and HARP syndrome (pallido-pyramidal syndrome and
      hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa and pallidal
      degeneration). From our series of patients one patient with PKAN and a
      progressive severe dystonic syndrome, cerebellar ataxia, retinitis pigmentosa and
      eventual anarthria had a novel combination of two compound heterozygote mutations
      identified in the PANK2 gene, G-->A transition at base 1238 (G411R) and a C-->A
      transition at base 1184 (A395E). In the patient with HARP syndrome two compound
      heterozygote mutations (Met327Thr and IVS5-1 G to T) in the PANK2 gene were
      found. No other mutations were found in any of the other patient groups,
      suggesting that PANK2 mutations are not associated with the aetiology of these
      adult degenerative conditions and confirms the genetic heterogeneity in
      neurodegeneration with brain iron accumulation.

PMID- 16962236
TI  - Ultrastructural features of hippocampal CA1 synapses with respect to synaptic
      enhancement following repeated PKA activation.
AB  - We reported previously that repeated activations, but not a single activation, of
      cyclic AMP-dependent protein kinase (PKA), led to a slowly developing (requiring
      approximately 1 week to develop) long-lasting (lasting > or = 3 weeks)
      enhancement of synaptic transmission efficiency in the organotypic slice culture
      of the rat hippocampus. It was accompanied by an increase in the number of
      synapses identified immunohistochemically. To answer the question of whether the
      "perforated synapse", which is known to occur transiently after the induction of
      long-term potentiation (LTP) in combination with the enlargement of postsynaptic
      density (PSD), is involved also in this slow/persistent synaptic enhancement, we
      examined the ultrastructural changes after the repeated activations of PKA. The
      answer was partially yes (occurrence of perforated synapses was increased) but
      partially no (the increase in the number of perforated synapses was not transient
      but persistent; mean apparent size of PSD did not increase). These results
      suggest that the mechanism of the slow/persistent synaptogenesis shares limited
      features with the mechanism of the quick/transient morphogenesis after LTP.

PMID- 16962237
TI  - Basal forebrain cholinergic lesions reduce heat shock protein 72 response but not
      pathology induced by the NMDA antagonist MK-801 in the rat cingulate cortex.
AB  - Non-competitive N-methyl-D-aspartate (NMDA) antagonists, in addition to their
      neuroprotective potential, possess neurotoxic properties and induce seizures and
      psychosis. MK-801 induces cytoplasmic vacuoles and heat shock protein in
      pyramidal neurones in the rodent posterior cingulate and retrosplenial cortex.
      The mechanism of this neurotoxicity is unclear, involving many neurotransmitter
      systems. The aim of this study was to investigate the role of cholinergic
      pathways from the nucleus basalis of Meynert in mediating MK-801-induced
      neurotoxicity. Cholinergic projections from the nucleus basalis of Meynert were
      lesioned by focal injection of 192-IgG-saporin (80 ng), which after 7 days
      reduced the number of cholinergic cell bodies by 70% in the lesioned nucleus
      compared to the uninjected nucleus. Following a unilateral cholinergic lesion, MK
      801 (5 mg/kg s.c.) induced expression of hsp72 mRNA (6 h) and HSP72 protein
      immunoreactivity (24 h) was reduced by 42 and 60%, respectively in the
      ipsilateral compared to the contralateral posterior cingulate. Despite this
      apparent protective effect, the unilateral cholinergic lesion did not affect the
      degree of neuronal vacuolation (6 h), necrosis (24 h) or the large and prolonged
      increase in cerebral blood flow which occurred over the first 9h following MK-801
      administration. These results demonstrate that cholinergic neurones in the
      nucleus basalis of Meynert play an important role in the heat shock response to
      NMDA antagonist-induced neurotoxicity but also reveal an unexpected divergence
      between the heat shock response and the pathophysiological response. This
      suggests that other cholinergic pathways or non-cholinergic mechanisms are
      responsible for the pathological changes induced by MK-801.

PMID- 16962239
TI  - A science of pain expression?

PMID- 16962238
TI  - Fear of movement/(re)injury in chronic pain: a psychometric assessment of the
      original English version of the Tampa scale for kinesiophobia (TSK).
AB  - The Tampa scale for kinesiophobia (TSK) was developed to measure fear of
      movement/(re)injury in chronic pain patients. Although studies of the Dutch
      adaptation of the TSK have identified fear of movement/(re)injury as an important
      predictor of chronic pain, pain-related avoidance behaviour, and disability,
      surprisingly little data on the psychometric properties of the original English
      version of the TSK are available. The present study examined the reliability,
      construct validity and factor structure of the TSK in a sample of chronic pain
      patients (n=200) presenting for an interdisciplinary functional restoration
      program. Consistent with prior evaluations of the Dutch version of the TSK, the
      present findings indicate that the English TSK possesses a high degree of
      internal consistency and is positively associated with related measures of fear
      avoidance beliefs, pain catastrophizing, pain-related disability and general
      negative affect. The TSK was not related to individual differences in physical
      performance testing as assessed using standardised treadmill and lifting tasks.
      Confirmatory factor analyses suggest that the TSK is best characterized by a
      three-factor trait method model that includes all 17 of the original scale items
      and takes into account the distinction between positively and negatively keyed
      items. The results of the present study provide important details regarding the
      psychometric properties of the original English version of the TSK and suggest
      that it may be unnecessary to remove the negatively keyed items in an attempt to
      improve scale validity.

PMID- 16962240
TI  - Preferential block of inactivation-deficient Na+ currents by capsaicin reveals a
      non-TRPV1 receptor within the Na+ channel.
AB  - Capsaicin elicits burning pain via the activation of the vanilloid receptor
      (TRPV1). Intriguingly, several reports showed that capsaicin also inhibits Na+
      currents but the mechanisms remain unclear. To explore this non-TRPV1 action we
      applied capsaicin to HEK293 cells stably expressing inactivation-deficient rat
      skeletal muscle Na+ mutant channels (rNav1.4-WCW). Capsaicin elicited a
      conspicuous time-dependent block of inactivation-deficient Na+ currents. The 50%
      inhibitory concentration (IC50) of capsaicin for open Na+ channels at +30 mV was
      measured 6.8+/-0.6 microM (n=5), a value that is 10-30 times lower than those for
      resting (218 microM) and inactivated (74 microM) wild-type Na+ channels. On-rate
      and off-rate constants for capsaicin open-channel block at +30 mV were estimated
      to be 6.37 microM(-1) s(-1) and 34.4 s(-1), respectively, with a calculated
      dissociation constant (KD) of 5.4 microM. Capsaicin at 30 microM produced
      approximately 70% additional use-dependent block of remaining rNav1.4-WCW Na+
      currents during repetitive pulses at 1 Hz. Site-directed mutagenesis showed that
      the local anesthetic receptor was not responsible for the capsaicin block of the
      inactivation-deficient Na+ channel. Interestingly, capsaicin elicited little time
      dependent block of batrachotoxin-modified rNav1.4-WCW Na+ currents, indicating
      that batrachotoxin prevents capsaicin binding. Finally, neuronal open Na+
      channels endogenously expressed in GH3 cells were as sensitive to capsaicin block
      as rNav1.4 counterparts. We conclude that capsaicin preferentially blocks
      persistent late Na+ currents, probably via a receptor that overlaps the
      batrachotoxin receptor but not the local anesthetic receptor. Drugs that target
      such a non-TRPV1 receptor could be beneficial for patients with neuropathic pain.

PMID- 16962241
TI  - Species diversity and seasonality of free-living ticks (Acari: Ixodidae) in the
      natural habitat of wild Marsh deer (Blastocerus dichotomus) in Southeastern
      Brazil.
AB  - This study evaluated the presence and seasonal activity of free-living ticks in
      remaining marsh areas by the Parana river, in Brazil. Eight field trips (once per
      season) for collection of ticks were performed during 2 years. Using CO2 traps,
      dragging, and visual inspection of vegetation, five free-living tick species were
      collected, in the following order of abundance: Amblyomma cajennense, Amblyomma
      dubitatum, Amblyomma triste, Amblyomma coelebs, and Amblyomma nodosum. The
      seasonal pattern of A. cajennense was characterized by the highest peaks for
      adult ticks in the summer/spring months, for nymphs in the winter and for larvae
      in the autumn and winter. A. dubitatum and A. triste presented similar seasonal
      patterns characterized by peaks of adult ticks in the autumn. Nymphs of A.
      dubitatum peaked in the winter of the first year and in the winter/spring of the
      second year. A. triste was the only species to be collected in significantly
      higher numbers in the marsh than in surrounding drier areas such as forest
      patches. Among domestic animals living close the marsh areas, horses were
      infested by Anocentor nitens, A. cajennense, and Boophilus microplus, bovines
      were infested solely by B. microplus, and dogs were infested by Rhipicephalus
      sanguineus. Adults of A. triste showed to be well adapted to the marsh
      environment. This result, at least partially, explains local previous
      observations on the association of A. triste with marsh deer, as this vertebrate
      host inhabits mainly the marsh area.

PMID- 16962242
TI  - Theileria parva infection in calves causes massive lymphocyte death in the
      thymus, spleen and lymph nodes without initial proliferation.
AB  - In a study of trends and magnitudes of lymphocytes proliferation, destruction or
      apoptosis eleven 3-month-old healthy calves were experimentally infected with the
      protozoan parasite Theileria parva, which is reported to cause lymphocyte
      proliferation. Four control calves were not infected. Infected and non-infected
      calves were sacrificed on days 9, 12, 16, 19, 23, 24 and 25 to examine lymphoid
      tissue changes and lymphocyte proliferation, apoptosis or necrosis in the thymus,
      spleen and lymph nodes. All infected calves developed severe East Coast fever,
      with enlargement of lymph nodes, dyspnoea, high fever and pulmonary oedema.
      Lymphocyte proliferation was not observed in lymph nodes, thymus and spleen;
      instead there were massive deaths of lymphocytes and other cells. The terminal
      severe disease caused massive lymphoid parenchyma coagulation terminating with
      caseation, organs and cells being undeterminable histologically. Tissues
      surrounding the lymph nodes were oedematous. Lymph node and thymus parenchyma
      were caseated and cortices and medulla indistinguishable because of severe
      lymphocyte and accessory cell deaths. The lymph node fibrous reticular stroma was
      necrotic and caseated. Lymphoid follicles in lymph nodes degenerated and lacked
      germinal centres. Lymph nodes, spleen and thymus were grossly enlarged, hardened,
      potato or cheese like, but microscopically very hypocellular and in the terminal
      disease acellular because of massive lymphocytes destruction. In the thymus there
      was extensive thymocyte and epithelioid cell necrosis and loss of distinction
      between cortex and medulla. The spleen white and red pulps were indistinguishable
      because of extensive lymphoid cell necrosis. The white pulp degenerated more than
      the red pulp. The massive lymphocyte deaths in the lymph nodes, thymus and
      spleen, without lymphocyte proliferation in this T. parva infection in calves
      leads to a conclusion that this parasite is lympho-destructive and lympho
      degenerative in vivo rather than lympho-proliferative.

PMID- 16962243
TI  - Macrocyclic lactone-resistant Parascaris equorum on stud farms in Canada and
      effectiveness of fenbendazole and pyrantel pamoate.
AB  - The aims of studies in 2002 and 2003 on three farms with 76 foals naturally
      infected with Parascaris equorum were to (i) identify if the nematode was
      resistant to ivermectin and moxidectin, and (ii) confirm the effectiveness of
      fenbendazole and pyrantel pamoate for the parasite. Twelve clinical trials, each
      with a Fecal Egg Count Reduction Test, were conducted on two Thoroughbred and one
      Standardbred farms in southwestern Ontario, Canada. In each trial, Parascaris
      eggs/g feces were estimated for each foal pre- and post-treatment using the
      Cornell-Wisconsin double flotation and Cornell-McMaster dilution techniques. On
      each farm and for each trial, foals were randomized into treatment groups.
      Treatments were ivermectin, moxidectin, fenbendazole, pyrantel pamoate
      administered at the manufacturers' recommended dosages, and some foals were
      untreated. The overall efficacy for ivermectin was 33.5% (19 foals) and for
      moxidectin 47.2% (28 foals). Fenbendazole (16 foals) and pyrantel pamoate (21
      foals) were highly effective for P. equorum each at 97.6%. For fenbendazole, 15
      foals had 100% and for pyrantel pamoate 17 foals had >97% with 14 at 100%.

PMID- 16962244
TI  - Swine infection with Trichinella spiralis: Comparative analysis of the mucosal
      intestinal and systemic immune responses.
AB  - The immune protective response developed by swine against Trichinella spiralis is
      not yet fully understood, particularly at the mucosal level. This study aimed to
      characterise intestinal immunity to T. spiralis by comparison with the systemic
      response in specifically pathogen-free pigs. For this purpose, the kinetics of
      cytokine and antibody production were assessed in the intestinal mucosa and serum
      of swine infected with T. spiralis for up to 60 days post-infection (dpi). An ex
      vivo model of jejunum mucosa culture was used to collect the supernatant as a
      source of antibodies (Abs). Mucosal antibodies were observed by Western blot from
      15 dpi, while serum antibodies were expressed from 20 dpi. Both sources of
      antibodies initially recognized a 110 kDa protein, followed by the identification
      of 35, 43/46 and 55/59 kDa proteins. IgG1 and IgA antibodies were strongly
      expressed within the mucosa. The expression levels of Type 1 (IFN-gamma, IL-12),
      Type 2 (IL-4, IL-6), pro-inflammatory (TNF-alpha) and regulatory (IL-10, TGF
      beta) cytokines were assessed by RT-PCR in the intestinal mucosa and spleen. Both
      IL-10 and IFN-gamma mRNA levels were increased in mucosa, whereas IL-6 and IL-12
      mRNA were expressed in spleen. Taken together, these results demonstrated a mixed
      Type 1/Type 2 profile, the Type 2 profile being dominant in the mucosa.

PMID- 16962245
TI  - A preliminary investigation of Ehrlichia species in ticks, humans, dogs, and
      capybaras from Brazil.
AB  - A molecular epidemiologic investigation in two Brazilian states (Rondonia and Sao
      Paulo) was undertaken to determine if Ehrlichia species responsible for human and
      animal ehrlichioses in North America could be found in Brazilian vectors,
      potential natural mammalian reservoirs and febrile human patients with a tick
      bite history. Samples, including 376 ticks comprising 9 Amblyomma species, 29
      capybara (Hydrochaeris hydrochaeris) spleens, 5 canine blood, and 75 human blood
      samples from febrile patients with history of tick bites were tested by a real
      time PCR assay targeting a fragment of the Ehrlichia dsb gene. Ehrlichia DNA was
      not detected in any tick, capybara or human samples. In contrast, 4 out of 5 dogs
      contained Ehrlichia canis DNA in their blood, which were sequenced, representing
      the first report of E. canis infecting dogs in the Amazon region of Brazil.
      Further studies are needed to evaluate the presence of other agents of human and
      animal ehrlichioses in Brazil.

PMID- 16962246
TI  - Epidemiology of flea infestation of ruminants in Libya.
AB  - The results of an epidemiological and clinical study of flea infestations of farm
      animals in northern Libya is reported. Of 12,130 sheep examined from 124 flocks,
      150 sheep were found to be infested with fleas from 50 different flocks. Likewise
      23 goats from 2981 examined, and 11 calves from 1124 cattle examined were
      infested No fleas were recovered from camels or horses. Of 1861 fleas recovered
      from farm livestock, 1857 were Ctenocephalides felis strongylus and 4 were Pulex
      irritans. Dogs from farms and local clinics were also examined. Eight farms dogs
      were found to be infested with P. irritans. Of 79 infested dogs examined in
      veterinary clinics, 53 were found infested with P. irritans, 11 with
      Ctenocephalides felis felis, 12 had a mixed infestation of P. irritans and C.
      felis felis. Single dogs had mixed infestation of P. irritans and C. canis; C.
      felis felis and C. canis; and P. irritans, C. felis felis and Echidnophaga
      gallinacia. C. felis felis was also found on 15 infested cats. C. felis felis was
      never found on large farm animals despite frequently sharing their environment
      with dogs or cats. Likewise C. felis stongylus was never isolated from dogs or
      cats. This is consistent with the hypothesis that C. felis strongylus has become
      adapted to large farm animals, whilst C. felis felis is better adapted to dogs
      and cats. However, four stockmen were found infested with a total of 176 C. felis
      strongylus, which suggests that this subspecies is also a potential zoonosis. A
      significantly higher proportion of intensive farms had animals with flea
      infestation compared to semi-intensive farms. Fleas were not found in nomadic
      herds. Infested farm animals often presented with excoriation, alopecia, pruritus
      and hyperkeratitis particularly on the lower limbs. These signs are consistent
      with the generation of flea-bite hypersensitivity.

PMID- 16962247
TI  - DNA arrays as predictors of efficacy of adjuvant/neoadjuvant chemotherapy in
      breast cancer patients: current data and issues on study design.
AB  - Chemotherapy provides variable benefit to patients with breast cancer, with
      usually modest but occasionally severe side effects. Hence, there is a need to
      identify predictive biomarkers for its efficacy. DNA arrays have been used in
      this setting as potential novel predictive diagnostic tools. Several gene
      signatures and single gene markers were proposed to predict response to
      chemotherapy. Although this technology offers interesting perspectives through
      large-scale analysis of the transcriptome, its ability to identify clinically
      relevant predictors is highly dependent on study design. In the present
      manuscript, we will review currently available results of breast cancer
      pharmacogenomics and focus on aspects of study design that are critical to
      reliably identify predictive biomarkers using DNA array technology. We will
      discuss whether studies should be done in the overall, unselected breast cancer
      population or in specific homogeneous molecular subclasses. Next, we will compare
      advantages and limitations of cohort-based and case-control studies. The choice
      of end-point to discriminate between sensitive and resistant patients will also
      be examined.

PMID- 16962248
TI  - Changes in salivary cortisol and corticosteroid receptor-alpha mRNA expression
      following a 3-week multidisciplinary treatment program in patients with
      fibromyalgia.
AB  - The aim of the present study was to investigate the effects of a 3-week
      residential multidisciplinary non-pharmacological treatment program (including
      individually prescribed aerobic exercise and cognitive-behavioral therapy) on
      fibromyalgia symptoms and hypothalamic-pituitary-adrenal (HPA) axis function.
      Salivary and venous blood samples were collected from 12 female patients with
      fibromyalgia (age: 25-58) the day before and the day after the treatment period:
      saliva, eight times (every two hours from 0800 to 2200 h); venous blood, at 0800
      h. Peripheral blood mononuclear cells (PBMC) were separated and analyzed for
      glucocorticoid receptor-alpha (GR-alpha) mRNA expression by semi-quantitative RT
      PCR, while the salivary cortisol concentration was determined by RIA. At the same
      time, pain and aerobic capacity were evaluated. Aerobic capacity improved at the
      end of the treatment program. The slope of the regression of salivary cortisol
      values on sampling time was steeper in all patients after treatment, indicating
      that the cortisol decline was more rapid. Concomitantly, the area under the
      cortisol curve "with respect to increase" (AUC(i)) was higher and there was a
      significant increase in GR-alpha mRNA expression in PBMC. The number of positive
      tender points, present pain, pain area and CES-D score were significantly reduced
      after the treatment, while the pressure pain threshold increased at most of the
      tender points. Our findings suggest that one of the active mechanisms underlying
      the effects of our treatment is an improvement of HPA axis function, consisting
      in increased resiliency and sensitivity of the stress system probably related to
      stimulation of GR-alpha synthesis by the components of the treatment.

PMID- 16962249
TI  - The role of antisocial and borderline personality features in substance
      dependence among incarcerated females.
AB  - This study examined the association of borderline personality disorder (BPD) and
      antisocial personality disorder (ASPD) with substance dependence among
      incarcerated females (N=105) as well as the influence of the co-occurrence of BPD
      and ASPD on psychosocial functioning in substance-dependent participants. The
      severity of BPD and ASPD both were associated with drug dependence, but BPD was
      not associated with alcohol dependence. After controlling for ASPD severity, BPD
      severity was no longer associated with drug dependence. The ASPD features of
      criminal activity and recklessness were most uniquely associated with drug and
      alcohol dependence (respectively). None of the BPD features was uniquely
      associated with alcohol or drug dependence after controlling for ASPD. A co
      occurring BPD diagnosis was associated with mood disturbance and experiential
      avoidance among substance-dependent participants. An ASPD diagnosis was
      associated with an earlier age at first arrest, along with greater childhood
      abuse and severity of alcohol dependence. These findings have important
      implications for further understanding and developing ways to help substance
      dependent incarcerated females.

PMID- 16962251
TI  - Renal corpuscle morphometry with increased reliability and high level of
      automation.
AB  - The paper presents an original computerized histometric technique for renal
      biopsies that outlines the role of quantitative information in the morphologic
      analysis of renal corpuscle (RC). We investigated 10 cases diagnosed as rapidly
      progressive glomerulonephritis (RPGN) by randomly selecting 10 RCs from each
      case. Our technique is based on two algorithms (implemented in the Zeiss KS400)
      that process digital color images for extracting the morphometric features at two
      levels: (1) of a single RC and (2) of a whole case. The algorithm operating at
      level (1) includes instruments especially designed for ensuring the accuracy in
      the identification of the regions occupied by the RC components; it evaluates the
      areas of the RC components and their percentages relative to the total area of
      the RC. The novelty of the instruments lies in the usage of intermediate
      recoloring for multifold thresholding segmentation and in the mutual validation
      of the regions provided by red-green-blue (RGB) and hue-lightness-saturation
      (HLS) segmentation. The algorithm operating at level (2) averages the data
      obtained from all the RCs considered in a case. The proposed technique offers a
      high level of automation; it is reliable and repeatable. The basic principles of
      the presented technique can also be adapted to the histometric approaches of
      other pathology domains. Results illustrate the utilization of the technique at
      both levels. The extraction of the RC morphometric features allows for
      establishing a significant correlation between the quantitative and qualitative
      information. This may contribute to a better understanding of the RPGN evolution
      and, implicitly, to the refinement of the diagnosis.

PMID- 16962250
TI  - DNA fragmentation factor (DFF45): expression and prognostic value in serous
      ovarian cancer.
AB  - This study investigated the expression of DNA fragmentation factor (DFF45), MIB
      1, and p53 in formalin-fixed, paraffin-embedded archival tissues of 50 ovarian
      serous carcinomas. In addition, 10 benign serous cystadenomas and 10 serous
      neoplasms of low malignant potential (LMP) were included in this DFF45
      immunostudy. With regard to quantity and intensity of positively stained cells,
      immunostaining for DFF45 was scored as low or strong. MIB-1 labeling indexes
      (LIs) were quantitated as the percentage of positively stained nuclei in 1000
      nuclei. For p53, at least 10% of tumor cells had to display nuclear staining to
      consider a case positive. DFF45 staining was noted predominantly in the nucleus.
      Low DFF45 expression was identified in all serous cystadenomas and in LMPs, as
      well as in 18 (36%) ovarian serous carcinomas. The latter displayed strong
      expression in 32 cases (64%). DFF45 immunoreactivity increased with FIGO stage
      and with grade (P=0.0213 and 0.0084, respectively), as well as with p53
      positivity (P=0.04), but not with MIB-1 LIs (P=0.076). A trend towards poor
      outcome was observed in patients whose tumors displayed high levels of DFF45
      immunoexpression (P=0.0187). Apoptotic bodies were consistently DFF45-negative.
      This study indicates that DFF45 expression is frequently upregulated in ovarian
      serous carcinomas and may serve as a marker of aggressive behavior with
      prognostic value.

PMID- 16962252
TI  - The effects of the Maillard reaction on the physical properties and cell
      interactions of collagen.
AB  - The non-enzymic glycation of collagen occurs as its turnover decreases during
      maturation, with complex carbohydrates accumulating slowly and the end-products
      of these reactions being permanent. The nature of these advanced glycation end
      reaction products (AGEs) can be categorised as: 1) cross-linking: intermolecular
      cross-linking may occur between two adjacent molecules and involve lysine to
      lysine or lysine to arginine residues. Several compounds have been characterised.
      They are believed to be located between the triple helical domains of adjacent
      molecules in the fibre resulting in major changes of the physical properties,
      primarily, fibre stiffness, thermal denaturation temperature and enzyme
      resistance, all of which increase slowly with age but the rate is accelerated in
      diabetes mellitus due to high glucose levels: 2) side-chain modifications: these
      changes alter the charge profile of the molecule affecting the interactions
      within the fibre and if they occur at specific sites can affect the cell-collagen
      interaction. Modification of arginine within the sites RGD and GFOGER recognised
      by the two specific integrins (alpha1beta2 and alpha2beta1) for collagen reduce
      cell interactions during turnover and for platelet interactions (alpha1beta2).
      These changes can ultimately affect repair of, for example, vascular damage and
      dermal wound healing in diabetes mellitus. Both types of modification are
      deleterious to the optimal properties of collagen as a supporting framework
      structure and as a controlling factor in cell matrix interactions. Glycation
      during ageing and diabetes is therefore responsible for malfunctioning of the
      diverse collagenous tissues throughout the body.

PMID- 16962253
TI  - Pictorial gaze cues do not enhance long-tailed macaques' performance on a
      computerised object-location task.
AB  - The perception of pictorial gaze cues was examined in long-tailed macaques
      (Macaca fascicularis). A computerised object-location task was used to explore
      whether the monkeys would show faster response time to locate a target when its
      appearance was preceded with congruent as opposed to incongruent gaze cues.
      Despite existing evidence that macaques preferentially attend to the eyes in
      facial images and also visually orient with depicted gaze cues, the monkeys did
      not show faster response times on congruent trials either in response to
      schematic or photographic stimuli. These findings coincide with those reported
      for baboons testing with a similar paradigm in which gaze cues preceded a target
      identification task [Fagot, J., Deruelle, C., 2002. Perception of pictorial gaze
      by baboons (Papio papio). J. Exp. Psychol. 28, 298-308]. When tested with either
      pictorial stimuli or interactants, nonhuman primates readily follow gaze but do
      not seem to use this mechanism to identify a target object; there seems to be
      some mismatch in performance between attentional changes and manual responses to
      gaze cues on ostensibly similar tasks.

PMID- 16962254
TI  - The association between change in social network characteristics and non-fatal
      overdose: results from the SHIELD study in Baltimore, MD, USA.
AB  - BACKGROUND: Social network factors have been reported to be associated with non
      fatal overdose. Yet, few studies have examined how changes in social network
      characteristics may influence overdose risk. The purpose of this study was to
      examine the relationship between changes in social network and non-fatal
      overdose. METHODS: Data for this study came from 659 participants enrolled in the
      Self-Help in Eliminating Life-Threatening Diseases (SHIELD) study, who reported
      details about their non-fatal overdose experience between enrollment and a follow
      up visit. Social network characteristics were described at both time points and
      net change in network composition was calculated. RESULTS: The sample was
      predominately male (56%), African-American (96%) and unemployed (78%). Experience
      of non-fatal overdose between time points was reported by 15%. Older age was
      associated with non-fatal overdose. Interaction between incarceration status and
      drug use was statistically significant. Protective factors were having a denser
      network at baseline and a network that became denser after adjusting for gender,
      homelessness, incarceration, drug use and total network size. CONCLUSIONS: Drug
      users' social networks are an important target for overdose prevention
      interventions. Further research on overdose risk and movement of specific network
      members in and out of networks is warranted.

PMID- 16962255
TI  - The effect of individual, program, and neighborhood variables on continuity of
      treatment among dually diagnosed individuals.
AB  - This study reviewed the medical charts of 271 patients diagnosed with co-morbid
      mental health and substance-use disorders who were discharged from a hospital
      acute inpatient unit to various outpatient treatment programs in Philadelphia.
      Geographic Information Systems (GIS) technology and logistic regression modeling
      were employed to investigate the effects of individual, neighborhood, and program
      level variables on arrival to the first treatment appointment within 30 days of
      discharge. Four models are presented. The results of the study suggest that
      having had three or more treatment episodes prior to inpatient hospitalization,
      and living in a neighborhood in which temporary or transitional, and presumably,
      other low income housing is located, increased the likelihood of patients
      continuing with treatment in the community. Discharge to the preadmission
      address, a chief complaint of bizarre behavior, close proximity of two or more
      liquor and/or beer stores, a high density of narcotics anonymous (NA) and/or
      alcoholics anonymous (AA) meetings within the neighborhood, an axis I diagnosis
      of substance-induced mood disorder, and a urine drug screen positive for heroin
      reduced the likelihood of attending outpatient treatment. We conclude that
      geographic and community variables as they relate to substance abuse may add an
      important dimension to our understanding of patient functioning and well being in
      the community following inpatient treatment.

PMID- 16962256
TI  - Phylogenomic analysis of non-ribosomal peptide synthetases in the genus
      Aspergillus.
AB  - Fungi from the genus Aspergillus are important saprophytes and opportunistic
      human fungal pathogens that contribute in these and other diverse ways to human
      well-being. Part of their impact on human well-being stems from the production of
      small molecular weight secondary metabolites, which may contribute to the ability
      of these fungi to cause invasive fungal infections and allergic diseases. In this
      study, we identified one group of enzymes responsible for secondary metabolite
      production in five Aspergillus species, the non-ribosomal peptide synthetases
      (NRPS). Hidden Markov models were used to search the genome databases of A.
      fumigatus, A. flavus, A. terreus, A. nidulans, and A. oryzae for domains
      conserved in NRPS proteins. A genealogy of adenylation domains was utilized to
      identify orthologous and unique NRPS among the Aspergillus species examined, as
      well as gain an understanding of the potential evolution of Aspergillus NRPS.
      mRNA abundance of the 14 NRPS identified in the A. fumigatus genome was analyzed
      using real-time reverse transcriptase PCR in different environmental conditions
      to gain a preliminary understanding of the possible functions of the NRPSs'
      peptide products. Our results suggest that Aspergillus species contain conserved
      and unique NRPS genes with a complex evolutionary history. This result suggests
      that the genus Aspergillus produces a substantial diversity of non-ribosomally
      synthesized peptides. Further analysis of these genes and their peptide products
      may identify important roles for secondary metabolites produced by NRPS in
      Aspergillus physiology, ecology, and fungal pathogenicity.

PMID- 16962257
TI  - No accelerated evolution of 3'UTR region in human for brain-expressed genes.
AB  - The difference in cognitive skills between humans and nonhuman primates is one of
      the major characters that define our own species. It was previously hypothesized
      that this divergence might be attributable to genetic differences at gene
      expression level, and the cis-regulating elements of gene 3'UTRs might play
      important roles in the post-transcriptional regulation of gene expression. In
      this study, we constructed a cDNA library from the prefrontal cortex of rhesus
      monkey and generated a total of 754 high-quality ESTs. Using rhesus macaque as
      outgroup, we calculated the evolutionary rates of the 3'UTRs of 52 brain
      expressed genes in humans and chimpanzees in order to dissect the role of natural
      selection during primate brain evolution. Comparison of 52 orthologous gene
      sequences of human and chimpanzee indicated that the mean substitution rates at
      nonsynonymous sites (K(a)), synonymous sites (K(s)) and 3'UTRs (K(3u)) are
      0.0024, 0.0116 and 0.0117, respectively. Relative rate tests and acceleration
      index tests demonstrated that only a few genes had significant rate divergence
      between human and chimpanzee. The 3'UTRs of the brain-expressed genes in primates
      has a similar evolutionary rate with the synonymous sites of the gene coding
      region, indicating a neutral evolution of the 3'UTR sequences in human.

PMID- 16962258
TI  - Characterization of a new beta-1,4-endoglucanase gene from the root-knot nematode
      Meloidogyne incognita and evolutionary scheme for phytonematode family 5 glycosyl
      hydrolases.
AB  - Cellulases from plant parasitic nematodes are encoded by multiple gene families
      and are thought to originate from horizontal gene transfer. Unraveling the
      evolution of these genes in the phylum will help understanding the evolution of
      plant parasitism in nematodes. Here we describe a new gene, named MI-eng-2, that
      encodes a family 5 glycosyl hydrolase (GHF5) with a predicted signal peptide and
      devoid of linker domain and cellulose-binding domain. The beta-1,4-endoglucanase
      activity of the protein MI-ENG-2 was confirmed in vitro and the transcription of
      the gene was localized in the secretory oesophageal glands of infective
      juveniles, suggesting that MI-ENG-2 is involved in plant cell wall degradation
      during parasitism. Phylogenetic and exon/intron structure analyses of beta-1,4
      endoglucanase genes in the order Tylenchida strengthen the hypothesis that
      nematode GHF5 genes result from horizontal gene transfer of a bacterial gene with
      a cellulose-binding domain. GHF5 gene families in Tylenchida result from gene
      duplications associated with occasional loss of the cellulose-binding domain and
      the linker domain during their evolution.

PMID- 16962259
TI  - Evaluation of LSSP-PCR for identification of Leptospira spp. in urine samples of
      cattle with clinical suspicion of leptospirosis.
AB  - We evaluated the use of low-stringency single specific primer PCR (LSSP-PCR) for
      genetically typing Leptospira directly from urine samples of cattle with clinical
      suspicion of leptospirosis. Urine samples obtained from 40 cattle with clinical
      suspicion of leptospirosis were amplified by specific PCR using the following
      primers: Internal 1/Internal 2 and G1/G2. The internal primers were designed from
      the gene sequence of the outer membrane lipoprotein Lip32 from Leptospira
      kirschneri, strain RM52. The PCR products were amplified with these two pairs of
      primers, which had approximately 497 and 285bp, respectively, and were
      subsequently used as a template for LSSP-PCR analysis. The genetic signatures
      from the leptospires which were present in the urine samples allowed us to make a
      preliminary identification of the leptospires by comparing the LSSP-PCR profiles
      obtained directly from urine samples with those from reference leptospires. The
      LSSP-PCR profiles obtained with the Internal 1 primer or with the G1 primer
      allowed the grouping of the leptospires into serogroups. LSSP-PCR was found to be
      a useful and sensitive approach capable of identifying leptospires directly from
      biological samples without the need for prior bacterial isolation. In conclusion,
      the LSSP-PCR technique may still be helpful in discriminating serogroups of
      Leptospira from different animal reservoirs, since the early identification of
      carrier animals and information on the shedding state are crucial to prevent the
      spread of leptospiral infection to other animals and humans.

PMID- 16962260
TI  - Identification of T-helper and linear B epitope in the hypervariable region of
      nucleocapsid protein of PPRV and its use in the development of specific
      antibodies to detect viral antigen.
AB  - Peste des petits ruminants is a highly contagious viral disease of small
      ruminants making its diagnosis difficult from the similar symptoms of Rinderpest.
      Computer based prediction algorithms was applied to identify antigenic
      determinants on the nucleocapsid (N) protein of PPRV. Specificity and
      antigenicity of each peptide was evaluated by solid phase ELISA. Six specific
      peptide sequences were evaluated in multiple antigenic peptide (MAP) form and
      immune response was evaluated by supplementing universal T-helper epitope human
      IL-1beta peptide (VQGEESNDK, amino acids 163-171). Out of the six peptides 19mer
      sequence corresponding to 454-472 region of N protein of PPRV was found to be
      highly immunogenic and specific to PPRV. Evaluation of overlapping peptides
      differing in length for this 452-472 region, showed minimum length of 14 amino
      acid residues were required for the stable affinity binding of antigen-antibody.
      The results of immunization and indirect ELISA indicated the presence of T-helper
      epitope at the N-terminal end and linear B epitope at the C-terminal region of
      454-472 19mer of nucleocapsid peptide of PPRV-nucleocapsid protein. The
      antipeptide antibodies developed against this region showed specificity to PPRV
      antigen differentiating it from RPV when used in indirect ELISA and western blot
      analysis.

PMID- 16962261
TI  - Greyhound meningoencephalitis: PCR-based detection methods highlight an absence
      of the most likely primary inducing agents.
AB  - Greyhound meningoencephalitis is currently classified as a breed-associated
      idiopathic central nervous system inflammatory disorder. The non-suppurative
      inflammatory response can be distinguished from the other breed-associated
      disorders based on histopathology and lesion topography, however the nature of
      the response primarily suggests a viral infection. In the present study PCR and
      RT-PCR technologies were employed on frozen cerebral tissue from confirmed cases
      of meningoencephalitis to target specific viruses and protozoa likely to be
      implicated and to exclude the presence of bacterial 16SrRNA. Secondly, degenerate
      primers were used to detect viruses of the herpesvirus and flavivirus families.
      In addition cerebral tissues were probed for West Nile Virus. Viral nucleic acid
      sequences to Borna disease virus, to louping ill, tick borne encephalitis, West
      Nile and other flaviviruses were not detected. Canine distemper virus was
      detected in one animal with 97% homology to strain A75/15. Degenerate PCR for
      herpesviruses detected viral amplification products in one animal with 90%
      homology to canine herpesvirus DNA polymerase gene. Protozoal amplification
      products were only detected in a single dog with pathological confirmation of a
      combination of lesions of greyhound meningoencephalitis and a protozoal
      encephalomyelitis. Neospora was confirmed with sequence homology to Austrian
      strain 1. Bacterial 16SrRNA was not detected. The present study supports previous
      observations that many of the known microbial causes of canine
      meningoencephalitis are not involved. Findings could reflect that the causal
      agent was not specifically targeted for detection, or that the agent is at
      undetectable levels or has been eliminated from brain tissue. The potential roles
      of genetics and of molecular mimicry also cannot be discounted.

PMID- 16962262
TI  - Evaluation of hemagglutinin subtype 1 swine influenza viruses from the United
      States.
AB  - Swine influenza viruses (SIV) of the hemagglutinin subtype 1 (H1) isolated from
      the United States (U.S.) have not been well-characterized in the natural host. An
      increase in the rate of mutation and reassortment has occurred in SIV isolates
      from the U.S. since 1998, including viruses belonging to the H1 subtype. Two
      independent animal studies were done to evaluate and compare the pathogenesis of
      10 SIV isolates dating from 1930 to currently circulating isolates. In addition,
      the hemagglutinin and neuraminidase genes of each isolate were sequenced for
      genetic comparison, and serological cross-reactivity was evaluated using all sera
      and virus combinations in hemagglutination inhibition and serum neutralization
      assays. Statistically significant differences in percentage of pneumonia and
      virus titers in the lung were detected between isolates, with modern isolates
      tending to produce more severe disease, have more virus shedding and higher viral
      titers. However, nasal shedding and virus titers in the lung were not always
      correlated with one another or lung lesions. Serologically, the classic
      historical H1N1 viruses tended to have better cross-reaction between historical
      sera and antigens, with moderate to good cross-reactivity with modern viral
      antigens. However, the modern sera were less reactive with historical viruses.
      Modern viruses tended to have less consistent cross-reactivity within the modern
      group. Overall, H1 isolates collected over the last 75 years from the U.S. pig
      population exhibit considerable variability in pathogenicity. There appears to be
      an increase in genetic and antigenic diversity coincident with the emergence of
      the swine triple reassortant H3N2 in 1998.

PMID- 16962263
TI  - Benzo(a)pyrene inhibits expression of inducible heat shock protein 70 in vascular
      endothelial cells.
AB  - Benzo(a)pyrene (BaP), a ubiquitous environmental pollutant known to cause many
      diseases including atherosclerosis, induces a dose-dependent reduction in the
      levels of the inducible Hsp70. To explore the mechanism underlying the reduction
      of Hsp70, we measured the levels of Hsp70, cytoplasmic and nuclear heat shock
      factor 1 (HSF1) in porcine aortic endothelial cells using Western blot, and then
      further characterized the binding ability of HSF1 and heat shock element (HSE) by
      electrophoretic mobility shift assay. We found that when porcine aortic
      endothelial cells were treated by 0.1-10 microM of BaP for 24 h, there was a
      significant reduction of Hsp70, cytoplasmic and nuclear HSF1 and the binding rate
      of HSF1 and HSE at 5, 10 microM of BaP but less effective at lower
      concentrations. The effect of BaP on the Hsp70 expression level was markedly
      attenuated by co-treatment with phorbol 12-myristate 13-acetate (PMA), an
      activator of protein kinase C (PKC). Staurosporine (STP), an inhibitor of PKC,
      blocked the effect of PMA treatment in combination with BaP. These results
      suggest that BaP might inhibit Hsp70 levels by reducing the expression of HSF1
      and decreasing binding of HSF1 and HSE via PKC-dependent signaling pathways that
      might be involved in the regulation of Hsp70 gene expression under BaP.

PMID- 16962264
TI  - Nutrition and fertility in dairy cattle. Proceedings of the symposium Dairy
      Solutions: Focus on Fertility, Dublin, Ireland, 27-28 October 2005.

PMID- 16962265
TI  - Prospects for improving reproductive performance through genetic selection.
AB  - Prospects for improving female fertility in dairy cattle using genetic selection
      are reviewed. Today's high producing cows have shorter estrous cycles, fewer
      standing events, shorter duration of estrus, and more frequent multiple
      ovulations. Although high milk production is often implicated as the cause of
      impaired fertility, the impact of inadequate body condition appears to be
      greater, as the latter has a significant impact on probability of conception,
      rate of embryonic loss, and proportion of anestrous animals. Genetic improvement
      of female fertility can be achieved by indirect selection for longevity or body
      condition score, or by direct selection for traits such as daughter pregnancy
      rate. Most leading dairy countries have implemented genetic evaluation systems
      for female fertility in the past decade, but refinement of these systems to
      account for hormonal synchronization, differences in the voluntary waiting
      period, exposure to natural service bulls, and other confounding factors is
      warranted. Recent work has focused on the development of data collection and
      genetic evaluation systems that will allow selection of bulls that have daughters
      that are resistant to common health disorders, including mastitis, lameness,
      ketosis, displaced abomasum, and metritis. Such systems will allow selection of
      animals that can remain healthy and fertile while producing large quantities of
      milk.

PMID- 16962266
TI  - Differential effects of progestogens, by type and regimen, on estrogen
      metabolizing enzymes in human breast cancer cells.
AB  - OBJECTIVES: To investigate the in vitro effects of five progestogens commonly
      used in hormone replacement therapy (HRT) on estrogen-metabolizing enzymes in
      human breast cancer cells. METHODS: The human hormone-dependent breast cancer
      cell lines T47D, MCF-7, and MCF-7aro were cultured with estradiol (E(2)) and
      progestogens. The mRNA levels of estrogen-metabolizing enzymes were determined by
      RT-PCR or Northern blot, and enzyme activities by radiolabeled substrates. Cell
      proliferation was measured by bromodeoxyuridine incorporation. In vitro models
      for continuous combined regimen (CCR) and sequential combined regimen (SCR) were
      established to mimic the in vivo conditions of HRT. RESULTS: Medroxyprogesterone
      acetate (MPA) plus E(2) (10(-8)M) stimulated the mRNA levels and activities of
      estrogen-activating enzymes aromatase (at 10(-8)M MPA), 17beta-hydroxysteroid
      dehydrogenase type 1 (17betaHSD1) (at 10(-6)M), and sulfatase (at 10(-8) to 10(
      6)M) compared to E(2) only. Progesterone also stimulated enzyme activity, but to
      a lower magnitude. Levonorgestrel, norethindrone, and dienogest showed no enzyme
      stimulation. The estrogen-inactivating enzymes 17beta-hydroxysteroid
      dehydrogenase type 2 and sulfotransferase were not affected by any of the
      progestogens tested. However, all the progestogens (at 10(-8) to 10(-6)M)
      inhibited E(2)-stimulated cell proliferation. While increased aromatase and
      17betaHSD1 activities were observed in the CCR model, no significant enzyme
      stimulation was observed in the SCR model. CONCLUSIONS: The present study
      suggested that progestogens exert different actions on estrogen-metabolizing
      enzymes in breast cancer cells dependent on the specific progestogen and regimen
      used. Further studies are needed to elucidate whether MPA, a progestogen
      currently used in HRT, leads to a higher risk of breast cancer development than
      other progestogens.

PMID- 16962267
TI  - A modified process for preparing cationic polylactide-co-glycolide microparticles
      with adsorbed DNA.
AB  - We have previously shown that cationic polylactide-co-glycolide (PLG)
      microparticles can be effectively used to adsorb DNA and generate potent immune
      responses in vivo. We now describe a modified and easier process containing a
      single lyophilization step to prepare these cationic PLG microparticles with
      adsorbed DNA. Cationic PLG microparticle formulations with adsorbed DNA were
      prepared using a modified solvent evaporation technique. Formulations with a
      fixed CTAB content and DNA load were prepared. The loading efficiency and 24h DNA
      release was evaluated for each formulation and compared to the earlier method of
      preparation. Select formulations were tested in vivo. The modified cationic PLG
      microparticle preparation method with a single lyophilization step, showed
      comparable physico-chemical behaviour to the two lyophilization steps process and
      induced comparable immune. The modified process with a single lyophilization step
      is a more practical process and can be utlized to prepare cationic PLG
      microparticles with adsorbed DNA on a large scale.

PMID- 16962268
TI  - Representation of acoustic signals in the human cochlea in presence of a cochlear
      implant electrode.
AB  - BACKGROUND: In subjects with remaining low frequency hearing, combined electric
      acoustic stimulation (EAS) of the auditory system is a new therapeutic
      perspective. Intracochlear introduction of a cochlear implant electrode, however,
      may alter the biomechanical properties of the inner ear and thus affect
      perception of acoustic stimuli. STUDY DESIGN: Based on histological observations
      of morphologic changes after cochlear implantation in cadaveric and post mortem
      studies the effects of basilar membrane (BM) stiffening in the ascending basal
      and middle turns of the cochlea due to close contact of the BM with the electrode
      were simulated in a 3D-computational finite element model of the inner ear. To
      verify our simulated results, pre- and postoperative pure-tone audiograms of 13
      subjects with substantial residual hearing, who underwent cochlear implantation,
      were evaluated. RESULTS: In the scenario of partial BM-fixation, acoustic energy
      of middle (2 kHz) and high (6 kHz) frequency was focused basally and apically to
      the fixed section, increasing BM displacement amplitudes up to 6 dB at a
      stimulation level of 94 dB (SPL). Lower frequencies were not affected by fixation
      in the basal and middle turn of the cochlea. In implanted subjects, a small but
      significant decrease of thresholds was observed at 1.5 kHz, a place in tonotopy
      adjacent to the tip region of the implanted electrode. CONCLUSION: Our model
      suggests that stiffening of the basilar membrane adjacent to an implanted
      electrode into the basal and middle cochlear turn did not affect BM movement in
      the low frequency area. Focussing of acoustic energy may increase perception in
      regions adjacent to the fixed section. Observations in implanted subjects were
      concordant with our model predictions. High frequencies, however, should not be
      amplified in patients using EAS to avoid disturbances in discrimination due to
      tonotopically incorrect frequency representation.

PMID- 16962269
TI  - Cochlear developmental defect and background-dependent hearing thresholds in the
      Jackson circler (jc) mutant mouse.
AB  - Jackson circler (jc) is a spontaneous, recessive mouse mutation that results in
      circling behavior and an impaired acoustic startle response. In this study, we
      refined the phenotypic and genetic parameters of the original jc mutation and
      characterized a new mutant allele, jc(2J). In open-field behavior tests,
      homozygous jc mutants exhibited abnormal circling and ambulatory behavior that
      was indistinguishable from that of phenotypically similar mutants with defects in
      the vestibule of the inner ear. The jc/jc and jc(2J)/jc(2J) mice had stable
      elevated auditory-evoked brainstem response (ABR) thresholds at the 16kHz
      stimulus of 88+/-9dB sound pressure levels (SPL) and 43+/-11dB SPL, respectively.
      Peak latencies and peak time intervals were normal in jc mutants. The jc mice
      showed no measurable distortion-product otoacoustic emissions (DPOAEs) above the
      system noise floor. In the mutant cochlea, the apical turn failed to form due to
      the developmental growth arrest of the cochlear duct at the level of the first
      turn at gestational day 13.5. In a large intrasubspecific intercross, jc
      localized to a 0.2cM interval at position 25cM on chromosome 10, which is
      homologous to the human 6q21 region. On CZECHII/Ei and CAST/Ei backgrounds jc/jc
      mutant hearing thresholds at the 16kHz stimulus were significantly lower than
      those observed on the C57BL/6J background, with means of 62+/-22dB SPL and 55+/
      18dB SPL, respectively. Genome-wide linkage scans of backcross, intercross, and
      congenic progeny revealed a complex pattern of genetic and stochastic effects.

PMID- 16962270
TI  - Course of hearing loss and occurrence of tinnitus.
AB  - Chronic tinnitus is often accompanied by a hearing impairment, but it is still
      unknown whether hearing loss can actually cause tinnitus. The association between
      the pitch of the tinnitus sensation and the audiogram edge in patients with high
      frequency hearing loss suggests a functional relation, but a large fraction of
      patients with hearing loss does not present symptoms of tinnitus. We therefore,
      investigated how the occurrence of tinnitus is related to the shape of the
      audiogram. We analyzed a sample where all patients had noise-induced hearing
      loss, containing 30 patients without tinnitus, 24 patients with tone-like
      tinnitus, and 17 patients with noise-like tinnitus. All patients had moderate to
      severe high-frequency hearing loss, and only minor to moderate hearing loss at
      low frequencies. We found that tinnitus patients had less overall hearing loss
      than patients without tinnitus. Moreover, the maximum steepness of the audiogram
      was higher in patients with tinnitus (-52.9+/-1.9 dB/octave) compared to patients
      without tinnitus (-43.1+/-2.4 dB/octave). Differences in overall hearing loss and
      maximum steepness between tone-like and noise-like tinnitus were not significant.
      For tone-like tinnitus, there was a clear association between the tinnitus pitch
      and the edge of the audiogram, with tinnitus pitch being on average 1.48+/-0.12
      octaves above the audiogram edge frequency, and 0.81+/-0.1 octaves above the
      frequency with the steepest slope. Our results suggest that the occurrence of
      tinnitus is promoted by a steep audiogram slope. A steep slope leads to abrupt
      discontinuities in the activity along the tonotopic axis of the auditory system,
      which could be misinterpreted as sound.

PMID- 16962271
TI  - Effects of three Chinese herbal medicines on plasma and liver lipids in mice fed
      a high-fat diet.
AB  - Chinese herbal medicines, Inchinko-to, Bofu-tsusho-san and Dai-saiko-to,
      containing 3, 18 and 8 components, respectively, have since long been used as an
      anti-inflammatory, antipyretic, choleretic and diuretic agent for liver disorders
      and jaundice, as an anti-obesity agent, a hypocholesterolemic agent for liver
      disorders and a therapeutic and/or preventive agent for cholesterol gallstone
      disease with hypertriglycerid-emia in China and Japan, respectively. In the
      present study, we investigated the effects of these three herbal medicines in
      young male mice fed a high-fat diet. Plasma levels of lipids and the numbers of
      the fatty droplets in the liver cytoplasm were markedly lowered by the diets
      supplemented with three herbal medicines. The liver weights and the body growth
      were reduced by the diet supplemented with Dai-saiko-to, which slightly affected
      the concentrations of total protein, albumin, creatinine or calcium, and the
      activity of lactate dehydrogenase. Thus, Dai-saiko-to, besides Bofu-tsusho-san,
      seems effective in the activities of anti-obesity, anti-hyperlipidemia and anti
      hyperlipids in liver cytoplasm, when used carefully.

PMID- 16962272
TI  - Appraisal of anti-inflammatory potential of the clubmoss, Lycopodium clavatum L.
AB  - Studies on four extracts prepared with petroleum ether, chloroform, ethyl acetate
      and methanol as well as the alkaloid fraction from the aerial parts of Lycopodium
      clavatum L. of Turkish origin using acetic acid-induced increase in capillary
      permeability assessment in mice revealed that only the chloroform extract and the
      alkaloid fraction displayed marked anti-inflammatory effect at a dose of 500mg/kg
      having percentage of inhibition 24.3 and 32.1, respectively, as compared to
      indomethacin, which exhibited 44.6% of inhibition at 10mg/kg dose. Bioassay
      guided fractionation of the alkaloid fraction of Lycopodium clavatum revealed
      that the alkaloidal-type of compounds might possibly be responsible for the anti
      inflammatory activity of the extract, which supports the folk medicinal
      utilization of the plant. Gas chromatographic-mass spectrophotometric analysis of
      the active alkaloid fraction revealed that lycopodine (84.5%) is the major
      component.

PMID- 16962273
TI  - Inhibitory effect of flavonoid baicalin on degranulation of human
      polymorphonuclear leukocytes induced by interleukin-8: potential role in
      periodontal diseases.
AB  - Baicalin is a flavonoid compound purified from the medicinal plant Scutellaria
      baicalensis Georgi and has been reported to possess anti-inflammatory activity
      through its ability to complex with chemokines and thus reduces the capacity of
      chemokines to bind and activate their receptors. In the present study, we
      investigated whether baicalin could block polymorphonuclear leukocytes (PMNs)
      degranulation induced by interleukin (IL)-8, a CXC chemokine. Human PMNs were
      isolated from the peripheral blood of periodontal healthy donors and incubated
      with various concentrations of IL-8 (preincubated with or without baicalin). The
      morphology of PMNs was examined by transmission electron microscopy and
      extracellular concentration of granule component matrix metalloproteinase-8 (MMP
      8) was detected by enzyme-linked immunosorbent assay (ELISA). Results showed that
      IL-8 could significantly induce MMP-8 release from PMNs when compared to control,
      and its inductive activity was concentration-dependent. But when preincubated
      with various concentrations of baicalin, the amount of MMP-8 release from PMNs
      decreased significantly. The present study concludes that baicalin could block
      MMP-8 release from PMNs induced by IL-8, which suggests that it may play an
      important role in the prevention and treatment of periodontal disease.

PMID- 16962274
TI  - "Mints", smells and traditional uses in Thessaloniki (Greece) and other
      Mediterranean countries.
AB  - The herbs of the "mint" group traded in the herbal market of Thessaloniki include
      eight taxa, members of two genera, Acinos (two species) and Mentha (four species
      and two hybrids). The essential oil content of 72 samples examined ranged from
      traces up to 1.69ml/100g of dry weight. Besides three almost scentless samples,
      the different "mints" are distinguished according to their prominent smell
      differences, i.e. samples with a pungent, musty and sweet type of smell. As a
      result, the commercial names attributed to them correspond to a particular type
      of smell and not to a particular taxon. A number of 29 medicinal uses were
      recorded in total. In most cases uses were not associated with particular taxa
      but were rather determined by plant smells. A literature survey has shown that
      the "mints" traded in Thessaloniki are also used as herbal medicines all over the
      Mediterranean area, with 67 different therapeutic uses. Among them the 22 uses,
      already mentioned by Dioscurides, show that the utilization of "mints" as herbal
      medicines in the Mediterranean countries has a long tradition.

PMID- 16962275
TI  - Mass spectral and NMR spectral data of two new designer drugs with an alpha
      aminophenone structure: 4'-methyl-alpha-pyrrolidinohexanophenone and 4'-methyl
      alpha-pyrrolidinobutyrophenone.
AB  - This study presents and discusses the nuclear magnetic resonance (NMR)
      spectroscopic and mass spectroscopic data of the new designer drug 4'-methyl
      alpha-pyrrolidinobutyrophenone (MPBP) and its homolog 4'-methyl-alpha
      pyrrolidinohexanophenone (MPHP) which were seized in 2004 and 2000 in Germany for
      the first time. The structure elucidation of the aliphatic part of MPBP was
      carried out by product ion spectroscopy of the immonium ion formed after electron
      ionization as well as with 1H and 13C NMR. Product ion spectroscopy of immonium
      ions again proved to be a powerful tool to determine the structure of designer
      drugs and to distinguish between isobaric structures of the alkyl-amino moiety.

PMID- 16962276
TI  - The role of the electron transport gene SDHC on lifespan and cancer.
AB  - Much attention has been focused on the hypothesis that oxidative damage
      contributes to cellular and organismal aging. A mev-1 mutation in the cytochrome
      b large subunit (SDHC) of complex II results in superoxide anion (O(2)(-))
      overproduction and therefore leads to apoptosis and precocious aging in the
      nematode Caenorhabditis elegans. To extend these data, a transgenic mouse cell
      line was constructed with a homologous mutation to mev-1. Many of the mutant
      nematode phenotypes (e.g., increased superoxide anion production, apoptosis) were
      recapitulated in the mouse. In addition, a significant fraction of the cells that
      survived apoptosis were transformed. These data support the notion that oxidative
      stress from mitochondria play an important role of both apoptosis, which leads to
      precocious aging, and cancer.

PMID- 16962277
TI  - Stress resistance in long-lived mouse models.
AB  - Cellular stress resistance has been observed in a variety of long-lived mouse
      systems. The Ames and Snell dwarf mice show altered hormonal profiles (low levels
      of growth hormone/IGF-1 and of other hormones). These altered hormonal profiles
      lead to physiological changes in cells, leading to increased resistance to
      multiple forms of stress including UV light, oxidative stress, heat, and the
      heavy metal cadmium. The cells also show resistance to carcinogen and senescence
      like growth arrest induced by ambient oxygen. Thus, cellular stress resistance
      may confer resistance to various diseases associated with stress insults. Stress
      resistance has also been observed in various long-lived mice (hemizygous knockout
      of igf-1r, a mutation in p66(shc), and klotho overexpression) and in vitro CR
      (Carolie Restriction) system. Many of the long-lived mouse systems show reduction
      or inhibition of the insulin/IGF-1-FOXO pathway, thus suggesting that there may
      be an overlapping mechanism for increased life span. The insulin/IGF-1-FOXO
      pathway interlocks to several signal transduction pathways through AKT, FOXO,
      JNK, and other components. Taken together, stress resistance may be an essential
      function in cells that leads to increased longevity. I will summarize molecular
      basis of stress resistance and further discuss stress resistance in other
      systems.

PMID- 16962278
TI  - Imaging features of benign adrenal cysts.
AB  - Benign adrenal gland cysts (BACs) are rare lesions with a variable histological
      spectrum and may mimic not only each other but also malignant ones. We aimed to
      review imaging features of BACs which can be helpful in distinguishing each
      entity and determining the subsequent appropriate management.

PMID- 16962279
TI  - Are the criteria of Tabar and Dean still relevant to radial scar?
AB  - OBJECTIVE: Aschoff's center of proliferation (ACP), poses significant problems of
      differential diagnosis both in imagery and histology with infiltrating carcinoma.
      Up to now the criteria of Tabar and Dean (classical criteria) are considered as
      diagnostically relevant. MATERIAL: A retrospective study of 113 cases, enabled us
      to study their clinical, radiological and histological aspects. RESULTS: The ACP
      is a subclinical and seldom palpable entity (12%). The radiological signs of ACP
      are quite variable. The classical criteria lack specificity and are observed only
      in 48% of our stellate images. Whereas the frequency of microcalcifications is
      high (58.5% of the cases), their presence and their type are not predictive of an
      associated malignancy. The echographic diagnosis of ACP could be made in 55% of
      the cases but the echographic semiology lacked specificity. We noticed an
      associated atypical epithelial hyperplasia in 28.5% of the cases, intraductal or
      lobular in situ carcinoma in 9% and/or a ductal invasive carcinoma in 2% of the
      cases. Neither tumor size, age of the patients, nor any radiological signs were
      predictive of such an association. CONCLUSIONS: The classical criteria are not
      completely reliable and are observed only in half of our stellate images, whereas
      microcalcifications are often present but are not predictive of an associated
      malignancy.

PMID- 16962280
TI  - Coronary calcium scoring with MDCT: the radiation dose to the breast and the
      effectiveness of bismuth breast shield.
AB  - OBJECTIVE: The purpose of our study was to determine the breast radiation dose
      during coronary calcium scoring with multidetector computerized tomography
      (MDCT). We also evaluated the degree of dose reduction by using a bismuth breast
      shield when performing coronary calcium scoring with MDCT. MATERIALS AND METHODS:
      The dose reduction achievable by shielding the adult (35 years or older) female
      breasts was studied in 25 women who underwent coronary calcium scoring with MDCT.
      All examinations were performed with a 16-MDCT scanner. To compare the shielded
      versus unshielded breast dose, the examinations were performed with (right
      breast) and without (left breast) breast shielding in all patients. With this
      technique the superficial breast doses were calculated. To determine the average
      glandular breast radiation dose, we imaged an anthropomorphic dosimetric phantom
      into which calibrated dosimeters were placed to measure the dose to the breast.
      The phantom was imaged using the same protocol. Radiation doses to the breasts
      with and without the breast shielding were measured and compared using the
      Student's t-test. RESULTS: The mean radiation doses with and without the breast
      shield were 5.71+/-1.1 mGy versus 9.08+/-1.5 mGy, respectively. The breast shield
      provided a 37.12% decrease in radiation dose to the breast with shielding. The
      difference between the dose received by the breasts with and without bismuth
      shielding was significant, with a p-value of less than 0.001. CONCLUSION: The
      high radiation during MDCT greatly exceeds the recommended doses and should not
      be underestimated. Bismuth in plane shielding for coronary calcium scoring with
      MDCT decreased the radiation dose to the breast. We recommend routine use of
      breast shields in female patients undergoing calcium scoring with MDCT.

PMID- 16962281
TI  - The levels of 5alpha-dihydrotestosterone in follicular fluid in healthy and
      atretic ovine follicles.
AB  - Dihydrotestosterone (DHT) induces follicular atresia under experimental
      conditions. However, whether it causes any antagonistic effect under natural
      condition is not known. In the present study, we investigated concentrations of
      DHT in follicular fluid and correlated them with concentrations of estradiol
      17beta (E2) and its androgen substrates, androstenedione (A4) and testosterone
      (T), in healthy and atretic follicles of sheep. Merino ewes were treated twice
      with PGF2alpha (PG) to synchronize estrus. The ovaries were recovered at 14 days
      after the second PG (luteal phase) or 24h after the third PG given 14 days after
      the second PG (follicular phase). Follicles were dissected and their size and
      appearance were recorded. Follicular fluid was collected from follicles larger
      than 3.5mm and concentrations of E2, progesterone (P4), A4, T and DHT were
      determined by RIA. The inhibitory effect of DHT on conversion of T to E2 was
      tested in cultured granulosa cells. Appreciable levels of DHT were observed in
      the follicular fluid of ovine preovulatory follicles. The levels of DHT were much
      lower than those of E2, A4 and T, irrespective of physiological conditions of
      follicles. No difference was found in DHT concentration between healthy and
      atretic follicles. Dihydrotestosterone marginally inhibited aromatization of T in
      granulosa cells but this effect was only observed when the levels of DHT were 10
      times higher than that of T in culture medium. These results indicate that DHT is
      present in ovine preovulatory follicles but its levels are not sufficient to
      exert any antagonistic effect on follicular development.

PMID- 16962282
TI  - Angiopoietins in malignancy.
AB  - BACKGROUND: Tumour growth is dependant upon the development of an adequate blood
      supply. This, in turn, is thought to depend upon a switch by the tumour, from a
      dormant to angiogenic state. Recent data suggest that this switch may occur when
      the balance of pro- and anti-angiogenic agents alters to promote angiogenesis.
      Angiopoietins may be involved in this balance. METHODS: An electronic literature
      search was performed with respect to angiopoietins from 1996 to the present.
      Published data from in-vitro and in-vivo studies were critically analysed. A
      specific focus was made of studies relating to tumour growth and vasculature.
      RESULTS: Since angiopoietin-1 was first described in 1996, three more
      angiopoietins have been described. All family members bind to the Tie-2 receptor.
      There is now a considerable accumulation of data that suggests they play a
      pivotal role in the development and stabilisation of tumour vasculature.
      angiopoietin-2 appears to be pro-angiogenic whilst angiopoietin-1 appears to be a
      stabilising factor. CONCLUSIONS: Recent trials of anti-angiogenic agents show
      promise in the treatment of solid human cancers. The angiopoietins are a new
      family of proteins that appear to be influential in the development of the tumour
      vasculature. Manipulation of the angiopoietin balance may provide a potential
      therapeutic target in human cancer.

PMID- 16962283
TI  - Kinetic characterization and in vitro toxicity evaluation of a luciferase less
      susceptible to HPV chemical inhibition.
AB  - Enzyme-based in vitro toxicity assays are often susceptible to inhibition by test
      compounds. A mutant luciferase selected to be less susceptible to inhibition by
      chloroform (CNBLuc03-06) and other high production volume (HPV) chemicals,
      consisting of three point mutations was created and characterized. The mutant
      luciferase was less inhibited by chloroform, other HPV chemicals and common
      surfactant release reagents (Triton-X and SDS) compared to the wild-type.
      Inhibition was shown to be competitive. CNBLuc03-06 was a factor of 1.5-3.2 more
      active than wild type and exhibited a much higher affinity for ATP. CNBLuc03-06
      was more thermostable than wild-type and also more active at pH values higher
      than 10. Both luciferases exhibited a significant tradeoff between activation and
      susceptibility to chemical inhibition in the presences of the reducing agent DTT.
      Inhibition to HPV chemicals was eliminated using an "optimum" formulation of DTT
      and co-solvent ethanol. The performance of CNBLuc03-06 in cell-based in vitro
      toxicity assays was shown to be superior to the current commercial formulation.

PMID- 16962284
TI  - Cleavage of tensin during cytoskeleton disruption in YTX-induced apoptosis.
AB  - Yessotoxin (YTX) is a marine algal toxin previously shown to induce apoptosis in
      L6 and BC3H1 myoblast cell lines. Disassembly of the F-actin cytoskeleton and
      cleavage of tensin, a cytoskeletal protein localised at the focal adhesion
      contacts, appear during this apoptotic process. Tensin binds to actin filaments
      at the focal adhesion contacts and it links the actin cytoskeleton to the
      extracellular matrix (ECM). This binding occurs via integrin receptors and it
      makes tensin a potential link between the actin cytoskeleton and signal
      transduction. This study evaluates disruption in the F-actin cytoskeleton and
      change of tensin in myoblast cell lines exposed to 100 nM YTX up to 72 h. YTX
      treatment cleaves tensin and makes it translocate to the cell centre. Tensin has
      normally a role in the maintenance of cell shape and YTX-treatment may therefore
      alter the shape of the cells. YTX exposure also induces formation of lamellas
      associated with pseudopodia. Alternative linkages and cytoskeletal proteins
      anchoring the actin filaments to focal contacts remain to be identified.

PMID- 16962285
TI  - The structure of worry: relations between positive/negative personality
      characteristics and the Penn State Worry Questionnaire.
AB  - The present studies investigated the structure, correlates, and predictors of
      worry, as assessed by the Penn State Worry Questionnaire (PSWQ), in a large
      nonclinical sample (N=1439). Exploratory factor analysis of the PSWQ in Study 1
      revealed a two-factor solution (Worry Engagement and Absence of Worry).
      Confirmatory factor analysis in Study 2 indicated that the two-factor solution
      provided a better fit to the data than a one-factor model. The PSWQ and its
      factors evidenced good internal consistency, and correlations with measures of
      positive and negative state-trait variables provided evidence for good convergent
      and discriminant validity in both studies. Evidence for the specificity of the
      two-factor solution was also found such that the Worry Engagement factor
      demonstrated higher correlations with negative state-trait variables than the
      Absence of Worry factor. However, path analyses in Study 3 examining predictors
      of worry provided support for a one-factor solution to the PSWQ. Furthermore,
      path analyses showed that trait anxiety significantly mediated the relationship
      between negative characteristics and worry, whereas trait anxiety inversely
      mediated the relationship between positive characteristics and worry. These
      findings support the use of the PSWQ in research examining the nature of worry
      and highlight how positive and negative characteristics may have unique relations
      with worry in the context of trait anxiety.

PMID- 16962286
TI  - Prenatal acoustic stimulation influences neuronal size and the expression of
      calcium-binding proteins (calbindin D-28K and parvalbumin) in chick hippocampus.
AB  - Prenatal auditory enrichment by species-specific sounds and sitar music enhances
      the expression of immediate early genes, synaptic proteins and calcium binding
      proteins (CaBPs) as well as modifies the structural components of the brainstem
      auditory nuclei and auditory imprinting area in chicks. There is also
      facilitation of postnatal auditory preference of the chicks to maternal calls
      following both types of sound stimulation indicating prenatal perceptual
      learning. To examine whether the sound enrichment protocol also affects the areas
      related to learning and memory, we assessed morphological changes in the
      hippocampus at post-hatch day 1 of control and prenatally sound-stimulated
      chicks. Additionally, the proportions of neurons containing calbindin D-28K and
      parvalbumin immunoreactivity as well as their protein levels were determined.
      Fertilized eggs of domestic chick were incubated under normal conditions of
      temperature, humidity, forced draft of air as well as light and dark (12:12h)
      photoperiods. They were exposed to patterned sounds of species-specific and sitar
      music at 65 dB for 15 min per hour over a day/night cycle from day 10 of
      incubation till hatching. The hippocampal volume, neuronal nuclear size and total
      number of neurons showed a significant increase in the music-stimulated group as
      compared to the species-specific sound-stimulated and control groups. However, in
      both the auditory-stimulated groups the protein levels of calbindin and
      parvalbumin as well as the percentage of the immunopositive neurons were
      increased. The enhanced proportion of CaBPs in the sound-enriched groups suggests
      greater Ca(2+) influx, which may influence long-term potentiation and short-term
      memory.

PMID- 16962287
TI  - Oxysterol-binding protein-related protein (ORP) 9 is a PDK-2 substrate and
      regulates Akt phosphorylation.
AB  - The oxysterol-binding protein and oxysterol-binding protein-related protein
      family has been implicated in lipid transport and metabolism, vesicle trafficking
      and cell signaling. While investigating the phosphorylation of Akt/protein kinase
      B in stimulated bone marrow-derived mast cells, we observed that a monoclonal
      antibody directed against phospho-S473 Akt cross-reacted with oxysterol-binding
      protein-related protein 9 (ORP9). Further analysis revealed that mast cells
      exclusively express ORP9S, an N-terminal truncated version of full-length ORP9L.
      A PDK-2 consensus phosphorylation site in ORP9L and OPR9S at S287 (VPEFS(287)Y)
      was confirmed by site-directed mutagenesis. In contrast to Akt, increased
      phosphorylation of ORP9S S287 in stimulated mast cells was independent of
      phosphatidylinositol 3-kinase but sensitive to inhibition of conventional PKC
      isotypes. PKC-beta dependence was confirmed by lack of ORP9S phosphorylation at
      S287 in PKC-beta-deficient, but not PKC-alpha-deficient, mast cells. Moreover, co
      immunoprecipitation of PKC-beta and ORP9S, and in vitro phosphorylation of ORP9S
      in this complex, argued for direct phosphorylation of ORP9S by PKC-beta,
      introducing ORP9S as a novel PKC-beta substrate. Akt was also detected in a PKC
      beta/ORP9S immune complex and phosphorylation of Akt on S473 was delayed in PKC
      deficient mast cells. In HEK293 cells, RNAi experiments showed that depletion of
      ORP9L increased Akt S473 phosphorylation 3-fold without affecting T308
      phosphorylation in the activation loop. Furthermore, mammalian target of
      rapamycin was implicated in ORP9L phosphorylation in HEK293 cells. These studies
      identify ORP9 as a PDK-2 substrate and negative regulator of Akt phosphorylation
      at the PDK-2 site.

PMID- 16962288
TI  - Cyclin A activity predicts clinical outcome in oral precancer and cancer.
AB  - Accurate, predictive assessment of the behaviour of oral cancers and precancers
      remains elusive. Increasing dysregulation of cell proliferation is a feature of
      carcinogenesis, and alterations in cyclin proteins regulating cell cycle
      progression are involved in enhanced cell proliferation. The authors of the
      present study have previously demonstrated increased proliferative activity in
      oral dysplastic lesions and poorly differentiated carcinomas, and hypothesize
      that cell proliferation can be used as a predictive agent in clinical management.
      In this preliminary study, immunohistochemical quantification of cyclin A
      expression was carried out for 33 excised oral lesions (ranging from mild
      dysplasia to invasive squamous cell carcinoma, SCC). Clinical outcome was
      determined as: no disease after 2 years follow-up, persistent disease, or further
      disease presentation. Labelling Indices (LIs) ranged from 5.5 to 32.1%, and
      whilst a trend to increased labelling in increasingly dysplastic and neoplastic
      tissue was seen, this was not statistically significant (P=0.06). High LIs were
      related to poor clinical outcome (P=0.003), suggesting a definite role for cyclin
      A measurement as a predictive tool in clinical management.

PMID- 16962289
TI  - The evaluation of antimuscarinic-induced convulsions in fasted rats after food
      intake.
AB  - The present study was performed to evaluate convulsions after food intake in
      fasted rats pretreated with scopolamine or atropine and to determine whether
      these convulsions respond to drugs found effective in fasted mice. Scopolamine
      (2.4 mg/kg) and atropine (2.4 mg/kg) were given intraperitoneally (i.p.) to rats
      fasted for 52h. Both drugs induced convulsions after animals were allowed to eat
      ad lib. Another group of fasted rats pretreated with saline, MK-801 (0.1mg/kg),
      clonidine (0.1mg/kg), chlorpromazine (2 and 4 mg/kg), valproate (200mg/kg),
      diazepam (1.5 and 2mg/kg) or gabapentin (50mg/kg) were treated i.p. with saline
      or scopolamine (2.4 mg/kg) and were allowed to eat ad lib. Clonidine, MK-801,
      chlorpromazine (4 mg/kg) and diazepam (2 mg/kg) reduced the incidence of
      scopolamine-induced convulsions in fasted rats. Gabapentin could only prolong the
      onset of convulsions. Neither treatment was effective against myoclonus of
      hindlimbs. Present results showed that fasted rats also develop antimuscarinic
      induced convulsions which do not completely respond to treatments found effective
      in convulsions of fasted mice.

PMID- 16962290
TI  - NR2B antagonists restrict spatiotemporal spread of activity in a rat model of
      cortical dysplasia.
AB  - Freeze-lesion-induced focal cortical dysplasia in rats closely resembles human
      microgyria, a neuronal migration disorder associated with drug-resistant
      epilepsy. Alterations in expression of N-methyl-D-aspartate receptors (NMDARs)
      containing NR2B subunits have been suggested to play a role in the
      hyperexcitability seen in this model. We examined the effect of NMDAR antagonists
      selective for NR2B subunits (Ro 25-6981 and ifenprodil) on activity evoked by
      intracortical stimulation in brain slices from freeze-lesioned rat neocortex.
      Whole-cell voltage-clamp recordings showed that Ro 25-6981 (1 microM)
      significantly reduced the response area of evoked postsynaptic currents in
      pyramidal cells from the paramicrogyral area whereas responses were unaffected in
      slices from control (sham operated) animals. Voltage-sensitive dye imaging was
      used to examine spatiotemporal spread of evoked activity in lesioned and control
      cortices. The imaging experiments revealed that peak amplitude, duration, and
      lateral spread of evoked activity in the paramicrogyral area was reduced by bath
      application of Ro 25-6981 (1 microM) and ifenprodil (10 microM). Ro 25-6981 had
      no effect on evoked activity in neocortical slices from control animals. The non
      selective NMDAR antagonist d-2-amino-5-phosphonvaleric acid (APV, 20 microM)
      reduced activity evoked in presence of 50 microM 4-aminopyridine (known to
      increase excitability by enhancing neurotransmitter release) in neocortical
      slices from control animals whereas Ro 25-6981 (1 microM) did not. These results
      suggest that NR2B subunit-containing NMDARs contribute significantly to the
      enhanced spatiotemporal spread of paroxysmal activity observed in vitro in the
      rat freeze-lesion model of focal cortical dysplasia.

PMID- 16962291
TI  - Effects of cerebrovascular risk factors on gray matter volume in adults aged 60
      64 years: a voxel-based morphometric study.
AB  - The effect of putative cerebrovascular risk factors on gray matter volume in a
      community-dwelling, non-demented 60- to 64-year-old cohort was investigated.
      Cranial T1-weighted MRI scans were obtained in 337 adults and voxel-based
      morphometric analyses were applied to detect regional gray matter volume
      differences related to hypertension, diabetes, smoking, and hyperlipidemia in men
      and women, respectively. Hypertension-related gray matter volume reduction was
      found in right superior, bilateral medial frontal, left superior temporal and
      left precentral gyri in men. No regional differences in gray matter related to
      hypertension were seen in women. Conversely, female but not male smokers had more
      gray matter volume in right fusiform gyrus and right temporal subgyral gray
      matter. No differences were observed in gray matter volume in association with
      diabetes or hyperlipidemia for men or women. Our results suggest that there are
      different patterns of regional effects in gray matter volume in relation to
      different cerebrovascular risk factors, and sex differences for the same risk
      factors.

PMID- 16962292
TI  - Mode of interaction of two fluorinated-hydrogenated hybrid amphiphiles with
      dipalmitoylphosphatidylcholine (DPPC) at the air-water interface.
AB  - Two-component Langmuir monolayers formed on 0.02 M Tris buffer solution (pH 7.4)
      with 0.13 M NaCl at 298.2K were investigated for two different fluorinated
      hydrogenated hybrid amphiphiles (F6PH5PPhNa and F8PH5PPhNa or F6 and F8,
      respectively) with DPPC. Surface pressure (pi), surface potential (DeltaV) and
      dipole moment (mu( perpendicular)) as a function of molecular surface area (A)
      were measured by employing the Whilhelmy method and an ionizing electrode method.
      From the A- and DeltaV-X(F6) (or X(F8)) curves, partial molecular surface area
      (PMA) and apparent partial molecular surface potential (APSP) were determined as
      a function of surface mole fraction (X(Fn)) at discrete surface pressures. Then,
      the behavior of occupied surface areas and surface potentials of the respective
      components could be made clearer. Compressibility (C(s)), elasticity (C(s)(-1)),
      and excess Gibbs energy (DeltaG((ex))) as a function of X(F6) (or X(F8)) were
      estimated at definite pressures. These physico-chemical parameters were found to
      reflect the mechanical strength of monolayer films formed. The regular solution
      theory being applied to DeltaG((ex)), the activity coefficients (f) as well as
      the interaction parameter (I(p)) between DPPC and two hybrid amphiphiles in the
      binary monolayers were evaluated. I(p) values thus obtained indicated that F8
      molecules interact more strongly with DPPC molecules than F6. Moreover, in order
      to better understand the morphological monolayer state, Langmuir-Blodgett (LB)
      films made from DPPC and fluorinated-hydrogenated hybrid amphiphiles were
      examined by atomic force microscopy (AFM). The miscibility of the two components
      in the monolayer state is evidenced by these thermodynamic quantities and AFM
      observations. Furthermore, AFM images demonstrated that F8 could more effectively
      disperse the ordered domains of DPPC than F6.

PMID- 16962293
TI  - Influence of parenteral fat emulsion Intralipos and citric acid on blood
      viscosity and erythrocyte morphology in vitro.
AB  - In most studies fat emulsion had been administered by enteral route. Recently a
      parenteral soybean-oil emulsion has been developed. In this study we assessed the
      effects of a parenteral soybean-oil emulsion (Intralipos) and citric acid on
      blood rheology and erythrocyte morphology in vitro. Porcine blood was incubated
      in vitro with increasing concentrations of fat emulsion Intralipos and citric
      acid at 37 degrees C for 1h. Viscosity of plasma and whole blood was measured
      using a FASCO-2050 digital viscometer. Red blood cell morphology was examined by
      light microscopy. The viscosity of whole blood represented an ascending dose
      dependence for different Intralipos concentrations at high shear rate of 90 and
      225 s(-1), however, it decreased with citric acid concentrations. On the other
      hand, the whole blood viscosity also declined with citric acid concentrations in
      presence of 30% Intralipos (v/v), and there is a minimal viscosity at 0.67%
      citric acid (v/v). There are some thorns on the blood membrane at 40% Intralipos
      as compared with control (no Intralipos addition), which indicates the Intralipos
      compound may affect blood cell membranes, and resulted in whole blood viscosity
      increase. We concluded that the intravenous soybean-oil preparation Intralipos
      interacts with the erythrocyte membrane, and citric acid could alleviate the
      whole blood viscosity.

PMID- 16962294
TI  - [Acute adrenal insufficiency in the newborn].
AB  - Neonatal acute adrenal insufficiency is a rare condition. Congenital adrenal
      hyperplasia with 21-hydroxylase defect appears to be the most frequent cause, but
      the neonatal screening has improved its potential severe outcome. The other
      causes and the various clinical presentations have been exposed, with a special
      reference to the salt-wasting syndrome. Among them, the severity of X-linked
      adrenal hypoplasia congenita (AHC) deserves special attention. Two other causes
      of adrenal hypoplasia have been recently discovered, i.e. a mutation of the SF-1
      gene and the syndrome IMAGe. Adrenal insufficiency secondary to ACTH deficiency
      is often unrecognised despite the risk of severe seizures and hypoglycaemia with
      brain damage. Finally, the hormonal diagnostic testing and the main therapeutic
      approach by corticosteroids have been indicated. The aim of this work is to focus
      the attention of paediatricians who examine a newborn because the risk of delayed
      diagnosis and fatal outcome may be limited if the clinical symptoms are soon
      recognized.

PMID- 16962295
TI  - Comparison between neural networks and multiple logistic regression to predict
      acute coronary syndrome in the emergency room.
AB  - OBJECTIVE: Patients with suspicion of acute coronary syndrome (ACS) are difficult
      to diagnose and they represent a very heterogeneous group. Some require immediate
      treatment while others, with only minor disorders, may be sent home. Detecting
      ACS patients using a machine learning approach would be advantageous in many
      situations. METHODS AND MATERIALS: Artificial neural network (ANN) ensembles and
      logistic regression models were trained on data from 634 patients presenting an
      emergency department with chest pain. Only data immediately available at patient
      presentation were used, including electrocardiogram (ECG) data. The models were
      analyzed using receiver operating characteristics (ROC) curve analysis,
      calibration assessments, inter- and intra-method variations. Effective odds
      ratios for the ANN ensembles were compared with the odds ratios obtained from the
      logistic model. RESULTS: The ANN ensemble approach together with ECG data
      preprocessed using principal component analysis resulted in an area under the ROC
      curve of 80%. At the sensitivity of 95% the specificity was 41%, corresponding to
      a negative predictive value of 97%, given the ACS prevalence of 21%. Adding
      clinical data available at presentation did not improve the ANN ensemble
      performance. Using the area under the ROC curve and model calibration as measures
      of performance we found an advantage using the ANN ensemble models compared to
      the logistic regression models. CONCLUSION: Clinically, a prediction model of the
      present type, combined with the judgment of trained emergency department
      personnel, could be useful for the early discharge of chest pain patients in
      populations with a low prevalence of ACS.

PMID- 16962296
TI  - A closed-loop hybrid physiological model relating to subjects under physical
      stress.
AB  - OBJECTIVE: The objective of this research study is to derive a comprehensive
      physiological model relating to subjects under physical stress conditions. The
      model should describe the behaviour of the cardiovascular system, respiratory
      system, thermoregulation and brain activity in response to physical workload.
      METHODS AND MATERIAL: An experimental testing rig was built which consists of
      recumbent high performance bicycle for inducing the physical load and a data
      acquisition system comprising monitors and PCs. The signals acquired and used
      within this study are the blood pressure, heart rate, respiration, body
      temperature, and EEG signals. The proposed model is based on a grey-box based
      modelling approach which was used because of the sufficient level of details it
      provides. Cardiovascular and EEG Data relating to 16 healthy subject volunteers
      (data from 12 subjects were used for training/validation and the data from 4
      subjects were used for model testing) were collected using the Finapres and the
      ProComp+ monitors. For model validation, residual analysis via the computing of
      the confidence intervals as well as related histograms was performed. RESULTS:
      Closed-loop simulations for different subjects showed that the model can provide
      reliable predictions for heart rate, blood pressure, body temperature,
      respiration, and the EEG signals. These findings were also reinforced by the
      residual analyses data obtained, which suggested that the residuals were within
      the 90% confidence bands and that the corresponding histograms were of a normal
      distribution. A higher intelligent level was added to the model, based on neural
      networks, to extend the capabilities of the model to predict over a wide range of
      subjects dynamics. CONCLUSION: The elicited physiological model describing the
      effect of physiological stress on several physiological variables can be used to
      predict performance breakdown of operators in critical environments. Such a model
      architecture lends itself naturally to exploitation via feedback control in a
      'reverse-engineering' fashion to control stress via the specification of a safe
      operating range for the psycho-physiological variables.

PMID- 16962297
TI  - Plasma phospholipid fatty acid composition as a biomarker of habitual dietary fat
      intake in an ethnically diverse cohort.
AB  - BACKGROUND AND AIM: As an evaluation of fatty acid intake measurement, our aim
      was to examine associations between diet and plasma phospholipid (PL) fatty
      acids, and whether these were modified by age, sex, country of birth, fasting
      status, use of cholesterol-lowering medication, body size, chronic disease and
      other lifestyle factors. METHODS AND RESULTS: Cross-sectional analysis of plasma
      PL fatty acid composition and dietary fatty acid intake over 12 months from a 121
      item food frequency questionnaire (FFQ) in 4439 men and women aged 40-69 years,
      born in Australia, Greece or Italy. Crude correlation coefficients ranged from
      0.18 to 0.40; and corrected correlation coefficients from 0.38 to 0.78 for total
      monounsaturated, polyunsaturated, n-6, n-3 fatty acids, oleic acid, linoleic
      acid, EPA and DHA. Weaker associations were observed for other fatty acids. The
      associations did not vary significantly by fasting status, use of lipid lowering
      medication or alcohol intake, but for some fatty acids did vary by sex, age, body
      mass index, country of birth, smoking and previous heart attack or diabetes.
      CONCLUSIONS: The FFQ provides useful information on intakes of mono- and
      polyunsaturated fatty acids. Correlations did not differ by fasting status, or
      use of lipid-lowering medication.

PMID- 16962298
TI  - Diffusion of naltrexone across reconstituted human oral epithelium and
      histomorphological features.
AB  - In transbuccal absorption a major limitation could be the low permeability of the
      mucosa which implies low drug bioavailability. The ability of naltrexone
      hydrochloride (NLX) to penetrate a resembling histologically human buccal mucosa
      was assessed and the occurrence of any histomorphological changes observed. We
      used reconstituted human oral (RHO) non-keratinised epithelium as mucosal section
      and a Transwell diffusion cells system as bicompartmental model. Buccal
      permeation was expressed in terms of drug flux (J(s)) and permeability
      coefficients (K(p)). Data were collected using both artificial and natural human
      saliva. The main finding was that RHO does not restrain NLX permeation. Drug
      transport across the epithelium was observed also in presence of various
      concentrations of penetration enhancers, without any significant differences. On
      the contrary, the flux throughout the mucosa was extensively affected by
      iontophoresis. Histologically, no sign of flogosis was observed in any specimen
      under experiment without iontophoresis, whereas cytoarchitectural changes, up to
      nuclear pycnosis or cellular swelling, were determined as a consequence of the
      application of electric fields.

PMID- 16962299
TI  - Sex-based divergence in head shape and diet in the Eastern lubber grasshopper
      (Romalea microptera).
AB  - Biologists are becoming increasingly aware of sex-based differences in
      ecologically important traits (locomotor performance, feeding morphology,
      thermoregulatory behavior). Yet, the overwhelming majority of these studies have
      been performed on vertebrates, despite often striking examples of sexual size
      dimorphism among the insects. Here, I tested whether adult male and female
      Eastern lubber grasshoppers differ in size/shape and feeding ecology. The
      morphological data clearly showed sex-based differences in several aspects of
      head and body size, with females being significantly larger in all aspects.
      Moreover, the sexes also differed in two aspects of size-adjusted morphology:
      head width and pronotum width, with females having relatively wider heads and
      thoraxes than males. Multiple regression analysis indicated that width of
      consumed foliage was positively related to pronotum width and foliage thickness
      was positively related to pronotum width, head width, and size-adjusted head
      width. Females consumed wider and thicker foliage (primarily smooth cord grass,
      Spartina alterniflora) than males, which most frequently consumed the narrow
      leafed forb hemp sesbania (Sesbania macrocarpa). Therefore, the sex-based
      differences in size and shape in this grasshopper are correlated with differences
      in consumed foliage shape.

PMID- 16962300
TI  - Fine structure of the organ of attachment of the teleost, Garra gotyla gotyla
      (Ham).
AB  - We describe the morphology of the attachment organ (AO) of the teleost, Garra
      gotyla gotyla (Cyprinidae). It is located ventrally around the mouth opening and
      used by the species for attachment to submerged rocks in sub-Himalayan streams
      and rivers where it lives. The AO consists of three crescentic parts and a
      central callus part. Scanning electron microscopy (SEM) shows the former to
      possess numerous tubercles, each of which bears about 23-27 curved spines. Light
      microscopy shows the epidermis of the tuberculated parts to possess one type of
      cell arranged into 7-8 rows. Transmission electron microscopy (TEM) reveals these
      cells to contain abundant tonofilaments (hence called the filament cells). The
      epidermis of the callus part possesses the filament cells and additionally mucous
      cells, which are absent in the tuberculated parts. The superficial epidermis is
      apparently keratinized (thickness: 5-8 microm), and a part of the cells of the
      outer row is modified into spines. These cells show a thick plasma membrane
      envelope and possess mucous granules (diameter: 0.1-0.3 microm) and bundles of
      tonofilaments. The cells of the inner two to four rows possess similar organelles
      and additionally, prominent Golgi bodies and rough endoplasmic reticulum.
      Immunohistochemically, the cells of the outer row and the spines stain positively
      for cytokeratin. The cells of the innermost rows (five to eight) possess few
      tonofilaments and no mucous granules. It is evident that the filament cells of
      the mid- to upper epidermis are specialized for the production of mucous granules
      and tonofilaments, which is unique for the teleost epidermis concerned. It
      appears that the tuberculated parts with spines assist in anchorage and
      interlocking with the substratum, while the central callus part probably utilizes
      both suction and frictional mechanisms, and mucous secretion protects the spines
      from damage during anchorage and abrasion.

PMID- 16962301
TI  - Hydrolysis of pectin: an enzymatic approach and its application in banana fiber
      processing.
AB  - Sediment samples were collected from different estuarine and marine areas along
      the West coast of India. Eighteen actinomycete cultures were isolated using
      starch casein agar and were screened for polygalacturonase activity by growing
      them on pectin-agar plates. Clear zones were visualized using 1% cetrimide. Out
      of the 18 strains screened ten cultures could effect hydrolysis of pectin. The
      above cultures were subjected to secondary screening under submerged
      fermentation. The actinomycete strain of Streptomyces lydicus was found to be a
      potent producer of polygalacturonase. Different growth media were screened for
      enzyme production and the best medium was selected for further studies. The crude
      enzyme was used for the treatment of raw banana fibers.

PMID- 16962302
TI  - Characterization of bacterial isolates from industrial wastewater according to
      probable modes of hexadecane uptake.
AB  - Bacterial isolates from industrial wastewater were characterized according to
      probable modes of hexadecane uptake based on data for cell surface
      hydrophobicity, emulsifying activity, glycoside content and surface tension of
      cell-free culture medium. The results obtained suggested that both modes of
      biosurfactant-enhanced hexadecane uptake by bacterial strains take place, direct
      uptake and alkane transfer. The increase in cell surface hydrophobicity and
      glycoside production by the strains suggested the existence of biosurfactant
      enhanced interfacial uptake of the alkane. Such mechanism is probably predominant
      for three isolates, Staphylococcus sp. HW-2, Streptococcus sp. HW-9 and Bacillus
      sp. HW-4. Secreted biosurfactants enhanced mainly alkane emulsification for most
      hydrophobic isolate Arthrobacter sp. HW-8, and micellar transfer for most
      hydrophilic isolate Streptococcus sp. HW-5. For other strains (67%) both
      mechanisms of biosurfactant-enhanced hexadecane uptake probably take place in
      similar degree, interfacial uptake and alkane emulsification. The results
      obtained could contribute to clarifying the natural relationships between the
      members of water ecosystem studied as well as will reveal potential producers of
      surface active compounds.

PMID- 16962303
TI  - Preparation and use of media for protease-producing bacterial strains based on by
      products from Cuttlefish (Sepia officinalis) and wastewaters from marine-products
      processing factories.
AB  - Cuttlefish powder (CFP) from Sepia officinalis by-products was prepared and
      tested as a fermentation substrate for microbial growth and protease production
      by several species of bacteria: Bacillus licheniformis, Bacillus subtilis,
      Pseudomonas aeruginosa, Bacillus cereus BG1, and Vibrio parahaemolyticus. All
      microorganisms studied grew well and produced protease activity when cultivated
      in medium containing only CFP indicating that the strains can obtain their carbon
      and nitrogen source requirements directly from whole by-product proteins.
      Moreover, it was found that the addition to the cuttlefish medium of diluted
      fishery wastewaters (FWW), generated by marine-products processing factories,
      enhanced the production of protease. Maximum activity was obtained when cells
      were grown in cuttlefish media containing 5-times or 10-times diluted FWW. Five
      times diluted FWW enhanced protease production by B. cereus BG1 and B. subtilis
      by 467% and 75% more than control media, respectively. The enhancement could have
      been due to the high organic content or high salts in FWW. As a result,
      cuttlefish by-products powder enriched with diluted FWW was found to be a
      suitable growth media for protease-producing strains. This new process, which
      converts underutilized wastes (liquid and solid) into more marketable and
      acceptable forms, coupled with protease production, can be an alternative way to
      the biological treatment of solid and liquid wastes generated by the cuttlefish
      processing industry.

PMID- 16962304
TI  - Antioxidant and anti-inflammatory effects of products from Croton celtidifolius
      Bailon on carrageenan-induced pleurisy in rats.
AB  - Croton celtidifolius Bailon, commonly known as Sangue-de-Adave or Pau-Andrade, is
      a tree found in the Atlantic forest of southern Brazil. It has been popularly
      used for the treatment of inflammatory and ulcerative disorders. Phytochemical
      analysis demonstrated the presence of flavonoids and proanthocyanidins in an
      ethyl acetate fraction (EAF) from C. celtidifolius Bailon. In this study, we have
      evaluated the effects of EAF and its sub-fractions (35 and 63, catechin) on
      inflammatory (cell migration and plasma extravasation) and oxidative (lipid
      peroxidation, superoxide dismutase (SOD) activity and superoxide anion
      production) parameters in carrageenan-induced pleurisy in rats. NO production was
      also measured by nitrite/nitrate levels. EAF and sub-fraction 63 (63SF) showed
      anti-inflammatory activity, as indicated by a reduction in plasma extravasation
      and cell migration (mainly polymorphonuclear leukocytes) to the pleural cavity.
      Furthermore, EAF treatment decreased the production of superoxide radical anion
      by cells isolated from the pleural cavity, while it did not affect the
      nitrite/nitrate levels in exudates. The results show that C. celtidifolius
      contains substances with antioxidant and anti-inflammatory activity that, at
      least in part, act by a modulation of oxidative stress by phenolic compounds.

PMID- 16962305
TI  - Forced chondrocyte expression of sonic hedgehog impairs joint formation affecting
      proliferation and apoptosis.
AB  - Proliferation and apoptosis are two fundamental processes that occur during limb
      development, and in particular in joint formation. To study the role of hedgehog
      proteins in limbs, we have misexpressed Sonic Hedgehog specifically in
      chondrocytes. We found that the appendicular skeleton was severely misshapen
      while pelvic and shoulder girdles developed normally. In particular, we detected
      fusion of the elbow/knee joint, no definite carpal/tarsal, metacarpal/metatarsal
      bones and absence of distinct phalanges, fused in a continuous cartilaginous rod.
      Molecular markers of joints, such as Gdf5 and sFrp2 were absent at presumptive
      joint sites and Tenascin C, a molecule associated with joint formation and
      expressed in permanent cartilage, was expressed in a wider region in transgenic
      animals as compared to the wild type. The ratio of proliferating to non
      proliferating chondrocytes was about two times higher in transgenic developing
      cartilage as compared to the wild type. Accordingly, the proapoptotic gene Bax
      was barely detectable in the growth plate of transgenic mice and Tunel assay
      showed the absence of apoptosis in presumptive joints at E15.5. Taken together,
      these results suggest that misexpression of Sonic Hedgehog causes apoptosis and
      proliferation defects leading to the lack of joint cavity and fusion of selected
      limb skeletal elements.

PMID- 16962306
TI  - Cultural symbolism of fish and the psychotropic properties of omega-3 fatty
      acids.
AB  - Fish is a food with unique psychotropic properties. Consumption of long-chain
      omega-3 fatty acids, rich in seafood, reduces depression, aggression and anger
      while improving mental well-being. We posit that symbols of fish have become
      linked to the emotional states induced by long-chain fatty acid by associative
      pairings, both conscious and unconscious. The limbic and hippocampal activity
      necessary for memory formation containing emotional content and the labeling of
      social context by cortical processes appears to be optimized by diets rich in
      long-chain omega-3 fatty acid. In this critical literature survey, we find that
      fish have been culturally labeled as symbols of emotional well-being and social
      healing in religious and medical practices among independent cultures, for at
      least six millennia. This understanding of the perception of fish as a
      symbolically healing or purifying food can assist current messages improving
      public health.

PMID- 16962307
TI  - Systemic corticosteroids in chronic obstructive pulmonary disease: an overview of
      Cochrane systematic reviews.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by symptoms of
      cough, sputum and breathlessness, which become worse during acute exacerbations.
      The airway inflammation associated with COPD has led to trials of the effect of
      systemic corticosteroids in COPD assessed in two Cochrane systematic reviews. In
      stable COPD, compared with placebo, oral corticosteroid treatment increased mean
      FEV(1) by 53 ml and mean 12-min walking distance by 29 m, but at an increased
      risk of any drug-related adverse event (OR 7.8). In acute exacerbations, oral
      corticosteroid treatment decreased the chance of treatment failure (OR 0.48),
      improved mean FEV(1) at 72 h by 140 ml and improved arterial blood gases, but
      increased the risk of drug-related adverse events (OR 2.3). Thus, treatment of
      stable and acute exacerbations of COPD with systemic corticosteroids results in
      statistically significant average benefits, but at an increased risk of adverse
      events. In stable COPD, there is little support for the use of systemic
      corticosteroid treatment, as data on long-term outcomes are lacking. For acute
      exacerbations, the evidence to support the use of systemic corticosteroids is
      stronger, but further research is required to define the optimum dose, route and
      duration.

PMID- 16962309
TI  - A novel microfluidic impedance assay for monitoring endothelin-induced
      cardiomyocyte hypertrophy.
AB  - Cardiac hypertrophy is an established and independent risk factor for the
      development of heart failure and sudden cardiac death. At the level of individual
      cardiac myocytes (heart muscle cells), the cell morphology alters (increase in
      cell size and myofibrillar re-organization) and protein synthesis is activated.
      In this paper, a novel cardiomyocyte-based impedance sensing system with the
      assistance of dielectrophoresis cell concentration is reported to monitor the
      dynamic process of endothelin-1-induced cardiomyocyte hypertrophy. A
      dielectrophoresis (DEP) microfluidic device is fabricated capable of
      concentrating cells from a dilute sample to form a confluent cell monolayer on
      the surface of microelectrodes. This device can increase the sensitivity of the
      impedance system and also has the potential to reduce the time for detection by a
      significant factor. To examine the feasibility of this impedance sensing system,
      cardiomyocytes are treated with endothelin-1 (ET-1), a known hypertrophic agent.
      ET-1 induces a continuous rise in cardiomyocyte impedance, which we interpret as
      strengthening of cellular attachments to the surface substrate. An equivalent
      circuit model is introduced to fit the impedance spectrum to fully understand the
      impedance sensing system.

PMID- 16962308
TI  - The case for Survivin as mitotic regulator.
AB  - Survivin has been proposed to inhibit apoptosis and to regulate cell division.
      However, controversy still exists as to whether Survivin can indeed execute these
      distinct functions and if Survivin somehow coordinates apoptosis and (abnormal)
      cell division. Recent evidence has demonstrated that Survivin acts as a subunit
      of the chromosomal passenger complex, which is essential for proper chromosome
      segregation and cytokinesis. Within this complex, the mitotic kinase Aurora B
      acts as the enzymatic core, whereas Survivin dictates chromosomal passenger
      complex localization. This function of Survivin appears to be conserved
      throughout evolution. Although these findings do not exclude a role for Survivin
      as apoptosis inhibitor, they make a very strong case for Survivin as mitotic
      regulator.

PMID- 16962310
TI  - A recombinant Fab fragment-based electrochemical immunosensor for the
      determination of testosterone in bovine urine.
AB  - This work describes the development of an electrochemical, recombinant Fab
      fragment-based immunosensor for the detection of testosterone in bovine urine.
      The sensor comprised of a testosterone conjugate on the surface of screen-printed
      electrodes, and recognition followed by an anti-testosterone Fab fragment. The
      use of an IgG-horseradish peroxidase conjugate determined the degree of
      competition. Chronoamperometry at a potential of +100 mV, was chosen to
      reductively measure the product of the catalysis of 3,3',5,5'
      tetramethylbenzidine catalysis. ELISA was primarily used to investigate the assay
      system, prior to transferring to SPEs. The final Fab-based sensor exhibited the
      linear range of 300-40,000 pg/ml with limit of detection of 90+/-13 pg/ml.
      Furthermore, the developed Fab sensor allowed for the determination of
      testosterone in bovine urine directly after dilution, omitting the necessity of
      extraction and hydrolysis. Comparison of administrated bovine urine samples
      between the developed Fab sensor and GC-MS data showed quantitative or semi
      quantitative results and enabled identification of suspicious samples for further
      extensive analysis by established analytical techniques. With simple sample
      preparation, low limit of detection, and good repeatability, the proposed method
      can offer alternative advantages as a primary screening tool for meat quality
      control.

PMID- 16962311
TI  - Peptides mediating interaction networks: new leads at last.
AB  - A growing number of protein interactions are found to be mediated by a large
      globular region in one protein binding to a comparatively short, peptide stretch
      in another. Regions that bind a common protein often show a similar sequence
      pattern or linear motif that mediates the binding. The past year has seen reports
      of new techniques that can uncover these motifs directly from interaction data.
      These studies have suggested that the fraction of interactions mediated by these
      regions is greater than previously anticipated. Concurrently, other work has
      demonstrated that it is possible to target these interactions using small
      molecules. Together these developments hold great promise for future efforts to
      target chemically precise details of complex systems.

PMID- 16962312
TI  - Axonal regulation of myelination by neuregulin 1.
AB  - Neuregulins comprise a family of epidermal growth factor-like ligands that
      interact with ErbB receptor tyrosine kinases to control many aspects of neural
      development. One of the most dramatic effects of neuregulin-1 is on glial cell
      differentiation. The membrane-bound neuregulin-1 type III isoform is an axonal
      ligand for glial ErbB receptors that regulates the early Schwann cell lineage,
      including the generation of precursors. Recent studies have shown that the amount
      of neuregulin-1 type III expressed on axons also dictates the glial phenotype,
      with a threshold level triggering Schwann cell myelination. Remarkably,
      neuregulin-1 type III also regulates Schwann cell membrane growth to adjust
      myelin sheath thickness to match axon caliber precisely. Whether this signaling
      system operates in central nervous system myelination remains an open question of
      major importance for human demyelinating diseases.

PMID- 16962313
TI  - Probing the transcriptome of neuronal cell types.
AB  - Distinct neuronal cell types acquire and maintain their identity by expressing
      different genes. Recently it has become feasible to measure this cell type
      specific expression by isolating and amplifying mRNA from small populations of
      fluorescently labeled neurons and probing this mRNA with microarrays. Prior to
      this, most neuronal gene expression studies used tissue homogenates or randomly
      selected single cells and were, therefore, not well suited to studying
      transcriptional differences between cell types. Microarray studies of purified
      cell types have enabled investigators to identify the transcriptional signatures
      of, for example, subtypes of pyramidal neurons and interneurons in the neocortex,
      modulatory dopaminergic and serotonergic neurons, and the striatal neurons that
      form the so-called 'direct' and 'indirect' pathways through the basal ganglia.
      These studies are opening up new approaches to understanding brain circuitry,
      plasticity and pathology and are refining the concept of the neuronal cell type.

PMID- 16962314
TI  - A trace of silence: memory and microRNA at the synapse.
AB  - Identifying the neural circuits that mediate particular behaviors and uncovering
      their plasticity is an endeavor at the heart of neuroscience. This effort is
      allied with the elucidation of plasticity mechanisms, because the molecular
      determinants of plasticity can be markers for the neurons and synapses that are
      modified by experience. Of particular interest is protein synthesis localized to
      the synapse, which might establish and maintain the stable modification of
      neuronal properties, including the pattern and strength of synaptic connections.
      Recent studies reveal that microRNAs and the RISC pathway regulate synaptic
      protein synthesis. Is synaptic activity of the RISC pathway a molecular signature
      of memory?

PMID- 16962315
TI  - Multinational clinical trials in oncology and post-trial benefits for host
      countries: where do we stand?
AB  - International collaboration has undoubtedly played a key role in the
      extraordinary progress we have witnessed in some areas of oncology in recent
      years. It has allowed us, for instance, to design trials large enough to depict
      very small benefits, as well as high-quality trials in less incident types of
      cancer. For different reasons, developing countries have also shown growing
      interest in this international effort and have been participating in many
      international trials. However, the ever-growing costs of novel anti-cancer
      treatments and technologies have created unprecedented difficulties for health
      economies in developing countries. Although the issue of individual benefit for
      patients must also be taken into account, the actual benefit for their society
      may be minimal. This paper discusses the ethics of including patients from non
      developed countries in clinical trials evaluating the role of treatments that are
      unlikely to be made available to them after the trial because of prohibitive
      costs. Upfront arrangements ensuring post-trial access to interventions that have
      been proven successful might be the best alternative to exclusion from the
      research.

PMID- 16962316
TI  - Prognostic significance of symptoms of hospitalised advanced cancer patients.
AB  - PURPOSE: To assess the prognostic value of symptoms in hospitalised advanced
      cancer patients. PATIENTS AND METHODS: A prospective analysis was performed of
      181 hospitalised patients referred to a Palliative Care Team. Comprehensive
      symptom questionnaire, functional status, estimated life expectancy and survival
      were assessed. Using a Cox regression model, a predictive survival model was
      built. RESULTS: Median survival: 53 d. Median number of symptoms: 4; 20 symptoms
      occurred in 10%. Multivariate analysis showed nausea, dysphagia, dyspnoea,
      confusion and absence of depressed mood as independent prognostic factors for
      survival (p<0.05) with relative risks of dying of 1.96, 1.81, 1.79, 2.35 and
      1.79, respectively. Patients with 2, 3 or 4 of these factors at the same time had
      a relative risk of dying of 2.7, 2.1 and 9.0, respectively. CONCLUSION: A cluster
      of factors comprising nausea, dysphagia, dyspnoea, confusion and absence of
      depressed mood may be used to accurately predict survival in hospitalised
      advanced cancer patients.

PMID- 16962317
TI  - High-grade glioma in children under 5 years of age: a chemotherapy only approach
      with the BBSFOP protocol.
AB  - The aim of this study was to evaluate a chemotherapy strategy that avoids
      radiotherapy in first-line treatment of young children with high-grade glioma. A
      total of 21 children under 5 years of age received the BBSFOP protocol,
      comprising seven cycles of three drug pairs (carboplatin/procarbazine,
      cisplatin/etoposide and vincristine/cyclophosphamide) administered over a 16
      month period. Radiotherapy was performed in case of recurrence/progression.
      Median age at diagnosis was 23 months. Histology was classified as World Health
      Organisation (WHO) grade III in 13 and grade IV in 8. Of the 13 children with a
      residual tumour, chemotherapy induced 2 partial responses (PR), 1 minor response
      (MR) and 1 stable disease (SD) with no recurrent disease. Five-year progression
      free survival was 35% and 5-year overall survival was 59%, with a median follow
      up of 5.2 years. At the last update, 12 children were alive (10 without
      radiotherapy). In conclusion, this study shows that an adjuvant chemotherapy
      first approach is safe and allows radiotherapy to be avoided in selected
      children.

PMID- 16962318
TI  - Expression of transcription factor Yin Yang 1 in human osteosarcomas.
AB  - The transcription factor Yin Yang 1 (YY1) is known to be present in some human
      cancer cell lines and its expression correlates with immune-mediated apoptosis.
      By using Western blot analysis, we have shown that the YY1 protein is strongly
      expressed in human osteosarcoma cells and localised mainly in the nucleus.
      Moreover, by using immunohistochemistry and RT-PCR techniques, we have analysed
      the expression of YY1 protein in biopsies from human osteosarcomas. The YY1
      protein was not detectable by immunohistochemistry in osteoid tissue. However,
      its expression was restricted to osteosarcoma tissues. These data were confirmed
      by densitometric analysis of RT-PCR for YY1 expression. Thus, YY1 gene activation
      appears to be an early event in the process of osteoblastic transformation and
      its detection may represent, together with the analysis of other established
      markers, a useful diagnostic tool in human osteosarcomas.

PMID- 16962319
TI  - Modelling of biological processes during aerobic treatment of piggery wastewater
      aiming at process optimisation.
AB  - A dynamic mathematical model was developed for the simulation of the aerobic
      treatment of piggery wastewater. This model includes the carbon oxidation, the
      nitrification and the denitrification. According to the experimental results
      obtained during this study, a modified version of the activated sludge model No.
      1 has been developed. The model includes (1) nitrite as intermediate of
      nitrification and denitrification, (2) the distinction between the anoxic
      heterotrophic yield and the aerobic heterotrophic yield, respectively equal to
      0.53 and 0.6 and (3) the first-order hydrolysis of the slowly biodegradable
      fraction. The calibration and the validation of the model was performed using
      experimental data from three experiments with two piggery wastewaters. A set of
      kinetic and stoichiometric parameters emerged from these tests. Except the
      kinetic of hydrolysis of the slowly biodegradable organic matter varying from 6
      to 25 gCOD(gCODday)(-1), all other parameters were similar for all experiments.
      The dissolved oxygen concentration was identified as the main variable
      influencing the nitrite accumulation during nitrification. In the calibrated
      model, the oxygen half-saturation coefficient of the ammonium oxidisers (0.3g
      O(2)m(-3)) was lower than for the nitrite oxidisers (1.1 gO(2)m(-3)), leading to
      nitrite accumulation when the dissolved oxygen concentration was low. Simulations
      with the proposed model could be very useful for improved design and management
      of biological treatment of piggery wastewaters, particularly in case of partial
      nitrification to nitrite directly followed by denitrification.

PMID- 16962320
TI  - Fixed-bed fermentation of rice straw and chicken manure using a mixed culture of
      marine mesophilic microorganisms.
AB  - A mixture of rice straw (80%) and chicken manure (20%) was pretreated and
      fermented to carboxylic acids by using a mixed culture of marine mesophilic
      microorganisms. Two sets of four fermentors, built from PVC pipes, were used for
      both biomass pretreatment and fermentation. Four 1L fermentors (F1-F4) were
      arranged in series, where liquid fermentation products were transferred from one
      fermentor to the other, to form a train. A liquid volume of 10mL and 15mL were
      transferred every four days for Trains A and B, respectively. The maximum total
      acid concentration for F1 in Train A was 34.2g/L and the maximum acid
      concentration in F2-F4 was approximately 44g/L. The maximum total acid
      concentration in F1 in Train B was 30.5g/L and the maximum acid concentration in
      F2-F4 was approximately 48g/L. The conversion in each of the fermentors in Train
      A varied from 0.821 to 0.879g VS digested/g VS fed and the yield was in the range
      0.489-0.609g total acids/g VS fed. The conversion and yield in Train B were 0.741
      0.914g VS digested/g VS fed and 0.563-0.669g total acids/g VS fed, respectively.
      The continuum particle distribution model (CPDM) predicted acid concentrations
      and retention times in the fixed-bed fermentation system with R(2) of 0.67-0.84
      in Trains A and B.

PMID- 16962321
TI  - Odour emissions from anaerobic piggery ponds. 2: improving estimates of emission
      rate through recognition of spatial variability.
AB  - Odour emission rates were measured for seven different anaerobic ponds treating
      piggery wastes at six to nine discrete locations across the surface of each pond
      on each sampling occasion over a thirteen month period. Significant variability
      in emission rates were observed for each pond. Measurement of a number of water
      quality variables in pond liquor samples collected at the same time and from the
      same locations as the odour samples indicated that the composition of the pond
      liquor was also variable. The results indicated that spatial variability was a
      real phenomenon and could have a significant impact on odour assessment
      practices. Considerably more odour samples would be required to characterise pond
      emissions than currently recommended by most practitioners, or regulatory
      agencies.

PMID- 16962322
TI  - Odour emissions from anaerobic piggery ponds. 1. Results of a three season, 14
      month survey.
AB  - Odour emission rates were measured for seven different anaerobic ponds treating
      piggery wastes at six to nine discrete locations across the surface of each pond
      on each sampling occasion over a 14-month period. Emission rate values varied
      between ponds, between seasons for the same pond and even for the same pond on
      different days of a sampling week. Average seasonal emission rates ranged from
      7.9 to 46.5OU/m(2)s, while average emission rates ranged from 16.0 to
      29.0OU/m(2)s. Factors potentially responsible for the variability in emission
      rates were investigated, including air and pond liquor temperatures, time of day
      of sample collection, season and the impact of a prolonged drought.

PMID- 16962323
TI  - Fermentability of eastern gamagrass, big bluestem and sand bluestem grown across
      a wide variety of environments.
AB  - Plant biomass has attracted interest as a feedstock for biofuels production, but
      much of this work has been focused on relatively few plant species. In this
      study, three relatively-unstudied species of warm-season perennial grasses, grown
      at multiple locations in the eastern and central US and harvested over a three
      year period, were examined for fermentability via in vitro ruminal gas production
      and dry matter digestibility assays, and near-infrared reflectance calibrations
      were developed for these fermentation parameters. Big bluestem (Andropogon
      gerardii Vitman) displayed greater fermentability than did sand bluestem
      (Andropogon hallii Hack) or eastern gamagrass [Tripsacum dactyloides (L.) L.],
      but displayed lower biomass yields. The bluestems also displayed lower N contents
      and less variation in fermentability over different growth environments
      (geographic locations and harvest years), suggesting a more consistent biomass
      quality than for eastern gamagrass. Thus, in addition to their use as forage for
      ruminant animals, bluestems may be of particular interest as feedstocks for
      bioconversion to ethanol and other products via direct microbial fermentation
      (consolidated bioprocessing) schemes, and thus merit additional efforts to
      enhance biomass yield potential.

PMID- 16962324
TI  - Characterization of manures from fish cage farming in Chile.
AB  - This study aims to characterize salmonid manures and to determine their potential
      use in agricultural soils. Sampling was carried out below salmon and trout cages
      in farms located in lakes and in the sea in the South of Chile during 2002-2003.
      Manure was analyzed for macronutrients, micronutrients and heavy metals. Results
      showed a high variability between samples and differences between sea and lake
      manure. Dry matter contents were low averaging c. 12-15%. Manures showed low OM
      contents with values <c. 15% and a neutral pH (c. 7.0). Both manures had low
      total N contents with values of <0.9%, more than 75% of which was in the organic
      form. Lake manure showed high contents of P (1.56%), Ca (3.89%), Fe (27,948 ppm),
      Mn (446 ppm), Al (31,789 ppm), As (5.13 ppm), Cd (1.04 ppm), Cr (18.8 ppm), Ni
      (12.3 ppm), Pb (3.5 ppm) and Zn (393 ppm). Sea manure had high contents of Mg
      (1.65% ppm), K (0.63%), Na (11.8%) and Cu (89 ppm). Salmonid manure had low
      nutrients and heavy metal contents and a potential use in agricultural soils,
      which could reduce the risks of water pollution on water from fish farming.

PMID- 16962325
TI  - Identification of novel inhibitors of UDP-Glc 4'-epimerase, a validated drug
      target for african sleeping sickness.
AB  - Novel inhibitors of Trypanosoma brucei and mammalian UDP-Glc 4'-epimerase were
      identified by screening a small library of natural products and commercially
      available drug-like molecules. The inhibitors possess low micromolar potency
      against the T. brucei and human enzymes in vitro, display a degree of selectivity
      between the two enzymes, and are cytotoxic to cultured T. brucei and mammalian
      cells.

PMID- 16962326
TI  - Rapid microwave-assisted fluorination yielding novel 5'-deoxy-5'-fluorouridine
      derivatives.
AB  - The preparation of (18)F-labeled ligands for positron emission tomography (PET)
      and the subsequent imaging have to be completed within a half-life of the neutron
      deficient isotope ((18)F=110 min). In this paper, we report a rapid fluorination
      approach to obtain 5'-deoxy-5'-fluoro-substituted uracil nucleoside analogues.
      Nucleophilic substitution at the 5'-position of the nucleosides was achieved
      within 45 min providing excellent yields of 75-92% by application of microwaves.

PMID- 16962327
TI  - The sentinel node concept: a critique of the critique.

PMID- 16962328
TI  - A new carbon fibre spring orthosis for children with plantarflexor weakness.
AB  - We tested a new orthosis with a carbon fiber spring constructed to enable energy
      storing during increasing dorsiflexion in mid-stance, and to use the energy at
      the end of stance phase to aid push-off. The orthosis was tested on children with
      plantarflexor weakness due to motor disorders. All subjects were tested with 3D
      gait analysis with both the new orthosis and with their regularly used orthosis.
      In this technical note, the results of three individuals are reported. The
      preliminary findings show increased dorsiflexion, altered knee kinematics and
      improved kinetic and temporo-spatial parameters. Although the carbon spring
      orthosis influenced the subjects' gait in different ways, we conclude that the
      tested subjects with plantarflexion weakness benefit from the carbon fiber spring
      orthoses during walking. The parents' and children's subjective impressions as
      acquired from a questionnaire were also positive.

PMID- 16962329
TI  - Valgus bracing in patients with medial compartment osteoarthritis of the knee. A
      gait analysis study of a new brace.
AB  - A new valgus brace was evaluated in 15 patients with medial osteoarthritis of the
      knee and a varus leg axis. Significant improvement of pain and function were
      found after 6 weeks of brace treatment. Gait analysis showed that the brace had a
      tendency of lowering the peak varus moment about the knee. This effect was more
      profound in the presence of higher initial varus deformity angle of the knee.
      Furthermore, bracing led to a small decrease of knee extension at the end of the
      swing phase and an increase of walking velocity. The mechanisms identified by
      gait analysis in this study may be of clinical importance for future developments
      in brace treatment.

PMID- 16962330
TI  - Synthesis of new chemical entities from paracetamol and NSAIDs with improved
      pharmacodynamic profile.
AB  - It was envisaged to combine high antipyretic activity of paracetamol into
      commonly used NSAIDs. To achieve this goal new chemical entities were synthesized
      by chemically combining paracetamol and NSAIDs, and biologically evaluated for
      their antipyretic, analgesic, anti-inflammatory and ulcerogenic potential. The
      acid chloride of parent NSAIDs was reacted with excess of p-aminophenol to yield
      the desired p-amidophenol derivatives (1B-7B). Acetate derivatives (1C-7C) of
      these phenols (1B-7B) were also prepared by their treatment with acetic
      anhydride, in order to see the impact of blocking the free phenolic group on the
      biological activity of the derivatives. All the synthesized p-amidophenol
      derivatives showed improved antipyretic activity than paracetamol with retention
      of anti-inflammatory activity of their parent NSAIDs. These compounds elicited no
      ulcerogenicity unlike their parent drugs.

PMID- 16962331
TI  - Inhibition of protein kinase C by dequalinium analogues: structure-activity
      studies on head group variations.
AB  - New dequalinium analogues and related heteroaromatic systems were synthesized and
      evaluated for inhibition of protein kinase Calpha. In vitro assays with
      recombinant human PKCalpha showed that the number of the aromatic ring head
      groups as well as their electron-richness, are critical factors that determine
      potency. The inhibitory strengths of the synthesized compounds are shown to
      correlate well with Mulliken charges on the head group ring nitrogen atoms making
      it possible to design likely candidate molecules having improved protein kinase
      Calpha inhibitory activity.

PMID- 16962332
TI  - Influence of terminal branching on the transdermal permeation-enhancing activity
      in fatty alcohols and acids.
AB  - In order to investigate the effect of terminal chain branching in the skin
      permeation enhancers, seven alcohols and seven acids with the chain length of 8
      12 carbons and terminal methyl or ethyl branching were prepared. Their
      transdermal permeation-enhancing activities were evaluated in vitro using
      theophylline as a model permeant and porcine skin, and compared to those of the
      linear standards. Terminal methyl branching increased the enhancing activity only
      in 12C acid, no effect was seen in the shorter ones. Terminal ethyl however
      produced a significant increase in activity. In the alcohols, the branching was
      likely to change the mode of action, due to a different relationship between the
      activity and the chain length.

PMID- 16962333
TI  - Identification of Photosystem I and Photosystem II enriched regions of thylakoid
      membrane by optical microimaging of cryo-fluorescence emission spectra and of
      variable fluorescence.
AB  - Oxygenic photosynthesis of higher plants requires linear electron transport that
      is driven by serially operating Photosystem II and Photosystem I reaction
      centers. It is widely accepted that distribution of these two types of reaction
      centers in the thylakoid membrane is heterogeneous. Here, we describe two optical
      microscopic techniques that can be combined to reveal the heterogeneity. By
      imaging micro-spectroscopy at liquid nitrogen temperature, we resolved the
      heterogeneity of the chloroplast thylakoid membrane by distinct spectral
      signatures of fluorescence emitted by the two photosystems. With another
      microscope, we measured changes in the fluorescence emission yield that are
      induced by actinic light at room temperature. Fluorescence yield of Photosystem
      II reaction centers varies strongly with light-induced changes of its
      photochemical yield. Consequently, application of moderate background irradiance
      induces changes in the Photosystem II fluorescence yield whereas no such
      modulation occurs in Photosystem I. This contrasting feature was used to identify
      regions in thylakoid membranes that are enriched in active Photosystem II.

PMID- 16962334
TI  - Characterization of asymmetric polymeric membranes by gas permeation.
AB  - Polycarbonate films (thickness 18, 25 and 38 microm) were irradiated by a beam of
      100MeV Ni7+ ion. The permeability for hydrogen and carbon dioxide was measured
      from both sides of membrane at increasing etching time. These membranes show
      larger permeability from the irradiation side, than the reverse side indicating
      the formation of conical tracks and asymmetrical membrane. The stopping range
      (Se) of 100MeV Ni7+ ion beam in polycarbonate is 22microm, for 18microm thick
      membrane the etching time at which the permeability increases rapidly is less
      than that of 38microm thick membrane, for both the gases. The difference in
      permeability from the two sides is attributed to the conical shape of the track
      generated by the ions. The controlled flow rate of the membrane leads to the
      design of a special type of gas filter.

PMID- 16962335
TI  - Interleukin-10 (IL-10) gene polymorphism as a potential host susceptibility
      factor in tuberculosis.
AB  - Several genes encoding for different cytokines may play crucial roles in host
      susceptibility to tuberculosis (TB), since the cytokine production capacity
      varies among individuals and depends on the cytokine gene polymorphism. The
      association of the cytokine gene polymorphisms with the development of TB was
      investigated in this study. DNA samples were obtained from a Turkish population
      of 81 patients with the different clinical forms of TB, and 50 healthy control
      subjects. All genotyping (IL-6, IL-10, IFN-gamma, TGF-beta and TNF-alpha)
      experiments were performed using sequence-specific primers PCR (PCR-SSP).
      Analysis of allele frequencies showed that IL-10 -1082 G allele frequency was
      significantly more common in TB patients than healthy controls (37.7% vs 23.0%,
      p: 0.014). No statistically significant differences were observed between the
      different clinical forms of the disease. These results suggest that the
      polymorphisms in IL-10 gene may affect susceptibility to TB and increase risk of
      developing the disease. To confirm the biological significance of our results,
      further studies should be performed on other population groups.

PMID- 16962337
TI  - Purification and characterization of the guinea pig sigma-1 receptor functionally
      expressed in Escherichia coli.
AB  - Sigma receptors once considered as a class of opioid receptors are now regarded
      as unique orphan receptors, distinguished by the ability to bind various
      pharmacological agents such as the progesterone (steroid), haloperidol (anti
      psychotic), and drugs of abuse such as cocaine and methamphetamine. The sigma-1
      receptor is a 223 amino acid protein, proposed to have two transmembrane
      segments. We have developed a scheme for the purification of the guinea pig sigma
      1 receptor following overexpression in Escherichia coli as a maltose binding
      protein (MBP) fusion and extraction with Triton X-100. Affinity chromatography
      using an amylose column and Ni2+ affinity column was used to purify the sigma-1
      receptor. The sigma-1 receptor purified by this method is a 26 kDa polypeptide as
      assessed by SDS-PAGE, binds sigma ligands with high affinity and can be
      specifically photoaffinity labeled with the sigma-1 receptor photoprobe, [125I]
      iodoazidococaine. Ligand binding using [3H]-(+)-pentazocine indicated that
      approximately half of the purified protein in Triton X-100 bound to radioligand.
      The MBP-sigma-1 receptor and the sigma-1 receptor in 0.5% triton were maximally
      stable for approximately two weeks at -20 degrees C in buffer containing 30%
      glycerol.

PMID- 16962336
TI  - Antipsychotic drugs disrupt normal development in Caenorhabditis elegans via
      additional mechanisms besides dopamine and serotonin receptors.
AB  - Antipsychotic drugs may produce adverse effects during development in humans and
      rodents. However, the extent of these effects has not been systematically
      characterized nor have molecular mechanisms been identified. Consequently, we
      sought to evaluate the effects of an extensive panel of antipsychotic drugs in a
      model organism, Caenorhabditis elegans, whose development is well characterized
      and which offers the possibility of identifying novel molecular targets. For
      these studies, animals were grown from hatching in the presence of vehicle
      (control) or antipsychotic drugs over a range of concentrations (20-160microM)
      and growth was analyzed by measuring head-to-tail length at various intervals.
      First-generation antipsychotics (e.g., fluphenazine) generally slowed growth and
      maturation more than second-generation drugs such as quetiapine and olanzapine.
      This is consistent with in vitro effects on human neuronal cell lines. Clozapine,
      a second-generation drug, produced similar growth deficits as haloperidol.
      Converging lines of evidence, including the failure to rescue growth with high
      concentrations of agonists, suggested that the drug-induced delay in development
      was not mediated by the major neurotransmitter receptors recognized by the
      antipsychotic drugs. Moreover, in serotonin-deficient tph-1 mutants, the drugs
      dramatically slowed development and led to larval arrest (including dauer
      formation) and neuronal abnormalities. Evaluation of alternative targets of the
      antipsychotics revealed a potential role for calmodulin and underscored the
      significance of Ca(2+)-calmodulin signaling in development. These findings
      suggest that antipsychotic drugs may interfere with normal developmental
      processes and provide a tool for investigating the key signaling pathways
      involved.

PMID- 16962338
TI  - Rare codon clusters at 5'-end influence heterologous expression of archaeal gene
      in Escherichia coli.
AB  - Proteins from hyperthermophilic microorganisms are attractive candidates for
      novel biocatalysts because of their high resistance to temperature extremes.
      However, archaeal genes are usually poorly expressed in Escherichia coli because
      of differences in codon usage. Genes from the thermoacidophilic archaea
      Sulfolobus solfataricus and Thermoplasma acidophilum contain high proportions of
      rare codons for arginine, isoleucine, and leucine, which are recognized by the
      tRNAs encoded by the argU, ileY, and leuW genes, respectively, and which are
      rarely used in E. coli. To examine the effects of these rare codons on
      heterologous expression, we expressed the Sso_gnaD and Tac_gnaD genes from S.
      solfataricus and T. acidophilum, respectively, in E. coli. The Sso_gnaD product
      was expressed at very low levels when the open reading frame (ORF) was cloned in
      pRSET and expressed in E. coli BL21(DE3), and was expressed at much higher levels
      in the E. coli BL21(DE3)-CodonPlus RIL strain, which contains extra copies of the
      argU, ileY, and leuW tRNA genes. In contrast, Tac_gnaD was expressed at similar
      levels in both E. coli strains. Comparison of the Sso_gnaD and Tac_gnaD gene
      sequences revealed that the 5'-end of the Sso_gnaD sequence was rich in AGA(arg)
      and ATA(Ile) codons. These codons were replaced with the codons commonly used in
      E. coli by polymerase chain reaction-mediated site-directed mutagenesis. The
      results of expression studies showed that a non-tandem repeat of rare codons is
      critical in the observed interference in heterologous expression of this gene. We
      concluded that the level of heterologous expression of Sso_gnaD in E. coli was
      limited by the clustering of the rare codons in the ORF, rather than on the rare
      codon frequency.

PMID- 16962339
TI  - Neuroanatomical correlates of penile erection evoked by photographic stimuli in
      human males.
AB  - The objective of this study was to identify the cerebral correlates of the early
      phase, and of low to moderate levels, of penile tumescence using for the first
      time a volumetric measure of the penile response. We hypothesized that (i)
      regions whose response had been found correlated with circumferential penile
      responses in previous studies would be identified with volumetric plethysmography
      and (ii) that other brain regions, including the amygdalae, would be found using
      the more sensitive volumetric measurement. In ten healthy males, functional
      magnetic resonance imaging (fMRI) was used to study brain responses to sexually
      stimulating photographs and to various categories of control photographs. Both
      ratings of perceived erection and penile plethysmography demonstrated an erectile
      response to the presentation of sexually stimulating photographs. Regions where
      the BOLD signal was correlated with penile volumetric responses included the
      right medial prefrontal cortex, the right and left orbitofrontal cortices, the
      insulae, the paracentral lobules, the right ventral lateral thalamic nucleus, the
      right anterior cingulate cortex and regions involved in motor imagery and motor
      preparation (supplementary motor areas, left ventral premotor area). This study
      suggests that the development of low levels of penile tumescence in response to
      static sexual stimuli is controlled by a network of frontal, parietal, insular
      and cingulate cortical areas and that penile tumescence reciprocally induces
      activation in somatosensory regions of the brain.

PMID- 16962340
TI  - Effects of human yolk sac endothelial cells on supporting expansion of
      hematopoietic stem/progenitor cells from cord blood.
AB  - In order to investigate the effects of human yolk sac-derived endothelial cells
      (hYSECs) on the expansion of human hematopoietic stem/progenitor cells (HS/PCs)
      from umbilical cord blood (UCB) in vitro, we purified hYSEC-like cells from 4-5
      week human yolk sacs, which were morphologically similar to endothelial cells and
      expressed CD31, CD144 and vWF characteristics of endothelial cells. Then we
      isolated CD34(+) cells from UCB in culture under three different conditions: with
      hematopoietic cytokines (CKs), contact-coculture or noncontact-coculture with
      hYSECs supplemented with CKs, and found that the contact-coculture system had the
      strongest expansion efficiency in the total cells' (TCs) ability to form HPP
      CFCs. Erythroid burst-forming units (BFU-E) increased 52.35-fold, 20.26-fold and
      27.77-fold, respectively, compared with pre-expansion. We detected that the mRNA
      of Notch ligands such as Jagged1, Delta1 and Delta4 could express in hYSECs after
      contacted culture with UCB-CD34(+) cells but not the noncontacted cells by RT-PCR
      analysis. Therefore, we concluded that the contact-coculture system supplemented
      with CKs could support the expansion of UCB-HS/PCs in vitro, especially high
      potential proliferative colony-forming cells (HPP-CFC) and BFU-E, perhaps owing
      to Notch signal pathway.

PMID- 16962342
TI  - How nursing personnel judge patients' pain.
AB  - The study examined how nurses, student nurses, and nurse's aides judge patients'
      level of pain from five indicators: facial grimacing, maintenance of abnormal
      body position, restriction of movement, complaints about pain, and signs of
      possible depression. In Toulouse, France, 214 participants were presented with 48
      vignettes describing an elderly patient suffering from osteoarthritis who showed
      various levels of these signs. The three most important factors in judging pain
      were the difficulty in making social contact with the patient, the patient's
      avoidance of changing position, and her avoidance of movements. The nurses put
      more emphasis on the difficulty in making social contact than did the student
      nurses and nurse's aides. In all groups, each sign of pain contributed
      independently and additively to the level of pain that the patient was thought to
      be experiencing.

PMID- 16962343
TI  - Low magnetic fields for flow propagators in permeable rocks.
AB  - Pulsed field gradient NMR flow propagators for water flow in Bentheimer sandstone
      are measured at low fields (1H resonance 2 MHz), using both unipolar and bipolar
      variants of the pulsed gradient method. We compare with propagators measured at
      high fields (1H resonance 85 MHz). We show that (i) measured flow propagators
      appear to be equivalent, in this rock, and (ii) the lower signal to noise ratio
      at low fields is not a serious limitation. By comparing different pulse
      sequences, we study the effects of the internal gradients on the propagator
      measurement at 2 MHz, which for certain rocks may persist even at low fields.

PMID- 16962344
TI  - Design and performance of a high pressure insert for use in a standard magic
      angle spinning NMR probe.
AB  - In this paper we describe the construction and performance of high pressure magic
      angle inserts made from the polymer PEEK. The inserts were designed to fit inside
      standard commercial 7 mm magic angle spinning rotors and spin at the maximum
      frequency of the probe. The sample volume of the inserts was 100 microL. A gas
      loading chamber that operates at room temperature is described. The performance
      of the inserts is discussed for a number of gases in terms of resolution as a
      function of spinning speed and leakage of the gas due to permeation through the
      polymer. Finally, some preliminary results are shown in relation to complex food
      materials.

PMID- 16962346
TI  - Expression of endothelin receptors in frog, chicken, mouse and human pigment
      cells.
AB  - Several reports have shown the participation of vasoactive endothelins (ETs) in
      the regulation of vertebrate pigment cells. In the present study, we identified
      ET receptors in pigment cells of vertebrate species by RT-PCR assays, and
      compared the differential expression of the various subtypes in each species by
      quantitative PCR. RT-PCR was performed with specific primers for ETC, ETA(X) or
      ETA in Xenopus laevis melanophores, ETA or ETB(2) in chicken melanocytes, ETA or
      ETB in murine (B-16, S-91 or Melan-A) or human (SK-Mel 23 or SK-Mel 28) melanoma
      cells, and the products obtained were confirmed by cloning and sequencing. The
      results showed the presence of ETA(X), but not ETA mRNA, and confirmed the
      expression of ETC in X. laevis melanophores. ETA and ETB(2) mRNAs were also
      demonstrated in chicken melanocytes. ETA and ETB receptor were identified in S
      91, B16 and Melan-A murine cells. In human melanoma cells, SK-Mel 23 and SK-Mel
      28, we confirmed the presence of ETB mRNA, and also found ETA mRNA. The
      comparison between the two subtypes present in the pigment cell of each species
      and among species demonstrated that the expression of ETAs in chicken, mouse, and
      human melanocytes is negligible, as is the expression of ETA(X) in Xenopus
      melanophores. The relative expression, as determined by quantitative PCR, was as
      follows: chicken ETB>SK-Mel 23 ETB>S91 ETB>>>Xenopus ETC, suggesting that the
      endothelin system plays a major role in avian and mammalian pigment cell
      regulation, as compared to lower vertebrates. The phylogenetic analysis revealed
      that subtype A receptors were probably the most primitive ET receptors, directly
      deriving from the ancestral type; all the other receptors, B subtypes and C,
      originated from diverse derivative molecules.

PMID- 16962345
TI  - Ciclesonide is more effective than budesonide in the treatment of persistent
      asthma.
AB  - BACKGROUND: Ciclesonide is a lung-activated inhaled corticosteroid that provides
      effective control of persistent asthma. The objective of this study was to
      compare the efficacy and safety of once-daily ciclesonide versus once-daily
      budesonide in patients with asthma. METHODS: A total of 399 patients with asthma
      were randomised to receive once-daily ciclesonide 320 microg ex-actuator
      (equivalent to 400 microg ex-valve) or once-daily budesonide 400 microg for 12
      weeks. The primary endpoint was forced expiratory volume in 1s (FEV(1)).
      Additional efficacy variables included forced vital capacity (FVC), peak
      expiratory flow (PEF), asthma symptoms, use of rescue medication and time to
      onset of effect. Adverse events were monitored throughout the study. RESULTS:
      Both ciclesonide and budesonide significantly increased FEV(1) from baseline (416
      and 321 ml, respectively; p<0.0001). The increase in FEV(1) was significantly
      greater in ciclesonide-treated patients (95% confidence interval: 0.016-0.174;
      p=0.019 versus budesonide). Similarly, ciclesonide and budesonide significantly
      improved FVC and PEF from baseline (p<0.0001), and significantly greater
      increases occurred with ciclesonide (p=0.034 and 0.019 versus budesonide,
      respectively). Analysis of morning PEF revealed an earlier onset of action for
      ciclesonide versus budesonide; a significant improvement was seen by day 2
      (p=0.039 versus baseline) with ciclesonide compared with day 7 for budesonide
      (p=0.047 versus baseline). Adverse events occurred with a similar incidence in
      both treatment groups. Neither treatment caused significant changes in urinary
      cortisol levels. CONCLUSION: Once-daily ciclesonide was more effective than once
      daily budesonide in improving FEV(1), FVC and PEF. Ciclesonide also had an
      earlier onset of action than budesonide in patients with persistent asthma. Both
      ciclesonide and budesonide had good safety and tolerability profiles.

PMID- 16962347
TI  - Detoxification rates of wild herbivorous woodrats (Neotoma).
AB  - The detoxification systems of mammalian herbivores are thought to have evolved in
      response to the ingestion of plant secondary compounds. Specialist herbivores
      consume high quantities of secondary compounds and are predicted to have faster
      rates of Phase 1 detoxification compared to generalist herbivores. We tested this
      hypothesis by comparing the performances of a specialist (Neotoma fuscipes) and
      generalist (Neotoma lepida) herbivore using hypnotic state assays. Herbivores
      foraging in nature were live trapped and injected with hexobarbital (100 mg/kg).
      We measured the length of time in the hypnotic state as the time in which the
      animal was unable to right itself twice in 30 s. The specialist metabolized
      hexobarbital 1.7 times faster than the generalist (F(1, 19) = 9.31, P = 0.007) as
      revealed by its significantly shorter time spent in the hypnotic state (56+/-9
      min vs. 87+/-8 min, respectively). The results are consistent with the hypothesis
      that specialists have faster rates of Phase 1 detoxification. This is the first
      evaluation of the detoxification capability of mammalian herbivores foraging
      under natural conditions. Hypnotic state assays have broad potential applications
      to the study of vertebrate-plant interactions.

PMID- 16962348
TI  - The cost of Latin American science Introduction for the second issue of CBP-Latin
      America.
AB  - Latin American researchers in science and engineering (S&E), including those in
      biology and biomedical sciences, are frequently exposed to unstable conditions of
      financial support, material and human resources, and a limited number of
      positions at public and private institutions. Such uncertainties impose
      continuous challenges for the scientific community which, in the best of cases,
      responds with careful planning and creativity, and in the worst scenario endures
      the migration of scientists to the USA or Europe. Still, the number of scientific
      publications from Latin American institutions in the last decade increased at a
      much faster rate than publications from the USA and Canada. A brief analysis per
      country of the gross domestic product (GDP) spent in research and development
      (R&D) and the S&E production reported by the Pascal bibliographic database
      suggests that the number and quality of S&E publications is directly proportional
      to the financial support for R&D. However, the investment in R&D in Latin America
      did not increase at the same rate (from 0.49 to 0.55% of GDP, from 1990 to 2003)
      at which S&E publications did in the same period (2.9-fold increase, from 1988 to
      2001). In Latin America, the traditional financial support for scientific
      research continues to be from federal and state government funds, associated in
      some cases with institutional funds that are mostly directed towards
      administrative costs and infrastructure maintenance. The aim of this introduction
      is to briefly discuss the production cost of articles published in refereed S&E
      journals, including the cost of the scientific research behind them, and, at the
      same time, to increase the awareness of the high quality of scientific research
      in Latin American institutions despite the many challenges, especially financial
      constraints, faced by their scientists. The second issue of Comparative
      Biochemistry and Physiology dedicated to Latin America ("The Face of Latin
      American Comparative Biochemistry and Physiology") celebrates, by means of 26
      manuscripts from five countries, the diversity and quality of biological science
      in the continent.

PMID- 16962349
TI  - Zinc attenuates forskolin-stimulated electrolyte secretion without involvement of
      the enteric nervous system in small intestinal epithelium from weaned piglets.
AB  - In a previous study, we found that secretagogue-stimulated electrolyte secretion
      was attenuated by dietary and serosal zinc in piglet small intestinal epithelium
      in Ussing chambers. Several studies show that the enteric nervous system (ENS) is
      involved in regulation of electrolyte and/or fluid transport in intestinal
      epithelium from many species. The aim of the present study is to examine the
      mechanisms behind the attenuating effect of zinc on electrolyte secretion and to
      study whether the ENS is involved in this effect of zinc in vitro. Twenty-four
      piglets (six litters of four piglets) were allocated randomly to one of two
      dietary treatments consisting of a basic diet supplemented with 100 mg zinc/kg
      (Zn(100)) or 2500 mg zinc/kg (Zn(2500)), as ZnO. All the piglets were killed at 5
      6 days after weaning and in vitro experiments with small intestinal epithelium in
      Ussing chambers were carried out. Furthermore, zinc, copper, alkaline phosphatase
      (AP) and metallothionein (MT) in mucosa, liver, and plasma were measured. These
      measurements showed that zinc status was increased in the Zn(2500) compared to
      the Zn(100) fed piglets. The in vitro studies did not confirm previous findings
      of attenuating effects of dietary zinc and zinc in vitro on the 5-HT induced
      secretion. But it showed that the addition of zinc at the serosal side attenuated
      the forskolin (FSK) (cAMP-dependent) induced ion secretion in epithelium from
      piglets fed with Zn(100) diet. Blocking the ENS with lidocaine or hexamethonium
      apparently slightly reduced this effect of zinc in vitro, but did not remove the
      effect of zinc. Consequently, it is suggested that zinc attenuates the cAMP
      dependent ion secretion mainly due to an effect on epithelial cells rather than
      affecting the mucosal neuronal pathway.

PMID- 16962350
TI  - Further characterization of the cathepsin L-associated protein and its gene in
      two species of the brine shrimp, Artemia.
AB  - The major cysteine protease in embryos and larvae of the brine shrimp Artemia
      franciscana is a heterodimer composed of a cathepsin L-like polypeptide of 28.5
      kDa and a 31.5 kDa polypeptide called the cathepsin L-associated protein or CLAP.
      In a previous study, CLAP was shown to be a cell adhesion protein containing two
      Fas I domains and two GTP/ATP binding sites known as Walker A and B motifs. Here,
      we have characterized CLAP and its genes to better understand the role of this
      protein in Artemia development. The polymerase chain reaction was used to
      investigate the structure of the CLAP gene in two species of Artemia, the New
      World bisexual diploid A. franciscana and the Old World parthenogenetic
      tetraploid Artemia parthenogenetica. The protein coding region of the CLAP gene
      from each species was 99.5% identical for a protein of 332 amino acids, while the
      3' non-coding region, representing nearly 45% of the gene, was only 86% identical
      between the two related species. However, while the CLAP gene is intronless in A.
      franciscana, in A. parthenogenetica the gene contained a mini-intron of 30 base
      pairs in the 3' non-coding region. The sequences representing the CLAP gene in A.
      franciscana and A. parthenogenetica have been entered into the NCBI database as
      AY757920 and DQ100385, respectively. Northern blot analysis showed that while the
      cathepsin L gene is expressed constitutively in Artemia franciscana embryos and
      young larvae, the CLAP gene is not expressed in late embryos and young larvae. In
      contrast, Western blots indicated that CLAP is present in developing embryos and
      young larvae, at least to the first larval molt, supporting results obtained
      previously showing CLAP's resistance to degradation by its dimeric partner,
      cathepsin L. At the protein level we showed that the GTP/ATP binding sites in
      CLAP are functional with rate constants of 0.024 and 0.022 for GTP and ATP
      hydrolase activity, respectively. GTP but not ATP also had a slight stimulatory
      effect on cathepsin L activity of the heterodimeric protease containing CLAP. Our
      results support the hypothesis that CLAP plays an important role in targeting and
      expression regulation of cathepsin L activity during early development of
      Artemia.

PMID- 16962351
TI  - 6-hydroxy-nicotine-inducible multilevel transgene control in mammalian cells.
AB  - The precise control of transgene expression is essential for biopharmaceutical
      manufacturing, gene therapy and tissue engineering. We have designed a novel
      conditional transcription technology, which enables reversible induction,
      repression and adjustment of desired transgene expression using the clinically
      inert 6-hydroxy-nicotine (6HNic). The 6-hydroxy-nicotine oxidase (6HNO) repressor
      (HdnoR), which manages nicotine metabolism in Arthrobacter nicotinovorans pAO1 by
      binding to a specific operator of the 6-hydroxy-nicotine oxidase (O(NIC)), was
      fused to the Krueppel-associated box protein of the human kox-1 gene (KRAB) to
      create a synthetic 6HNic-dependent transsilencer (NS) that controls chimeric
      mammalian promoters, which are assembled by cloning tandem O(NIC) operators 3' of
      a constitutive promoter. In the absence of 6HNic, NS binds to O(NIC) and silences
      the constitutive promoter, which otherwise drives high-level transgene expression
      when the NS-O(NIC) interaction stops in the presence of 6HNic. Generic NICE(ON)
      technology was compatible with a variety of constitutive viral and mammalian
      housekeeping promoters, each of which enabled specific induced, repressed,
      adjusted and reversible transgene expression profiles in Chinese hamster ovary
      (CHO-K1), baby hamster kidney (BHK-21) as well as in human fibrosarcoma (HT-1080)
      cells. NICE(ON) also proved successful in controlling multicistronic expression
      units for coordinated transcription of up to three transgenes and in the fine
      tuning of transcription-translation networks, in which RNA polymerase II- and III
      dependent promoters, engineered for 6HNic responsiveness, drove expression of
      siRNAs that triggered specific transgene knockdown. NICE(ON) represents a robust
      and versatile technology for the precise tuning of transgene expression in
      mammalian cells.

PMID- 16962352
TI  - Introducing glutathione biosynthetic capability into Lactococcus lactis subsp.
      cremoris NZ9000 improves the oxidative-stress resistance of the host.
AB  - This study describes how a metabolic engineering approach can be used to improve
      bacterial stress resistance. Some Lactococcus lactis strains are capable of
      taking up glutathione, and the imported glutathione protects this organism
      against H(2)O(2)-induced oxidative stress. L. lactis subsp. cremoris NZ9000, a
      model organism of this species that is widely used in the study of metabolic
      engineering, can neither synthesize nor take up glutathione. The study described
      here aimed to improve the oxidative-stress resistance of strain NZ9000 by
      introducing a glutathione biosynthetic capability. We show that the glutathione
      produced by strain NZ9000 conferred stronger resistance on the host following
      exposure to H(2)O(2) (150 mM) and a superoxide generator, menadione (30 microM).
      To explore whether glutathione can complement the existing oxidative-stress
      defense systems, we constructed a superoxide dismutase deficient mutant of strain
      NZ9000, designated as NZ4504, which is more sensitive to oxidative stress, and
      introduced the glutathione biosynthetic capability into this strain. Glutathione
      produced by strain NZ4504(pNZ3203) significantly shortens the lag phase of the
      host when grown aerobically, especially in the presence of menadione. In
      addition, cells of NZ4504(pNZ3203) capable of producing glutathione restored the
      resistance of the host to H(2)O(2)-induced oxidative stress, back to the wild
      type level. We conclude that the resistance of L. lactis subsp. cremoris NZ9000
      to oxidative stress can be increased in engineered cells with glutathione
      producing capability.

PMID- 16962353
TI  - Effect of the global redox sensing/regulation networks on Escherichia coli and
      metabolic flux distribution based on C-13 labeling experiments.
AB  - Escherichia coli has several elaborate sensing mechanisms for response to the
      availability of oxygen and the presence of other electron acceptors. Among them,
      the one component Fnr protein and the two-component Arc system coordinate the
      adaptive responses to oxygen availability. To systematically investigate the
      contribution of Arc- and Fnr-dependent regulation in catabolism, glucose-limited
      chemostat cultures were conducted on wild-type E. coli, an arcA mutant, an fnr
      mutant, and an arcAfnr double mutant strains under a well-defined semi-aerobic
      condition. The metabolic flux distributions of the cultures of these strains were
      estimated based on C-13 labeling experiments. It was shown that the oxidative
      pentose phosphate (PP) pathway was functioning at low level under semi-aerobic
      condition. The fluxes through pyruvate dehydrogenase (PDH) and tricarboxylic acid
      (TCA) cycle were found to be lower in the arcA mutant and the arcAfnr double
      mutant strains than that in the wild-type strain, although the expression of the
      genes involved in these pathways have been proved to be derepressed in the mutant
      strains ([Shalel-Levanon, S., San, K.Y., Bennett, G.N., 2005a. Effect of ArcA and
      FNR on the expression of genes related to the oxygen regulation and the
      glycolysis pathway in Escherichia coli under microaerobic growth conditions.
      Biotechnol. Bioeng. 92, 147-159; Shalel-Levanon, S., San, K.Y., Bennett, G.N.,
      2005c. Effect of oxygen, and ArcA and FNR regulators on the expression of genes
      related to the electron transfer chain and the TCA cycle in Escherichia coli.
      Metab. Eng. 7, 364-374]). The significantly higher lactate production in the
      arcAfnr double mutant strain was shown to be an indirect effect caused by the
      reduced pyruvate formate-lyase (PFL) and PDH fluxes as well as the intracellular
      redox state.

PMID- 16962355
TI  - [Elective radiotherapy of the regional lymph node areas in breast cancer].
AB  - In breast cancer patients, the incidence of involvement of the regional lymph
      nodes and the risk for developing a locoregional recurrence are highly influenced
      by several prognostic factors. A meta-analysis of the EBCTCG showed a reduction
      of about 70% of the locoregional recurrence rate with radiotherapy for all
      patients, independent of age, characteristics of the tumour or the administration
      of systemic treatment. At the same time, this meta-analysis confirmed that
      radiotherapy can lead to an increased risk for developing contralateral breast
      cancer and to an increase in the risk of non-breast cancer related mortality,
      mainly due to cardiac and pulmonary toxicity. Because of this, the net effect of
      regional radiotherapy will be strongly influenced by the individual risk factors
      of the patients and by the quality of the technical aspects of the radiotherapy.
      The thin line between the benefits of elective regional lymph node irradiation
      and the possible late toxicity for patients with early stage breast cancer is
      currently the subject of several prospective randomised trials, the results of
      which will only become available in several years. Moreover, recent developments
      in the field of novel prognostic factors will open completely new ways to be
      explored, which might give us new tools for estimating the individual
      benefit/risk ratio for every single patient.

PMID- 16962356
TI  - Differential gene expression by Paracoccidioides brasiliensis in host interaction
      conditions: representational difference analysis identifies candidate genes
      associated with fungal pathogenesis.
AB  - Paracoccidioides brasiliensis causes infection by the host inhalation of airborne
      propagules of the mycelia phase of the fungus. These particles reach the lungs,
      and disseminate to virtually all organs. Here we describe the identification of
      differentially expressed genes in studies of host-fungus interaction. We analyzed
      two cDNA populations of P. brasiliensis, one obtained from infected animals and
      the other an admixture of fungus and human blood thus mimicking the hematologic
      events of the fungal dissemination. Our analysis identified transcripts
      differentially expressed. Genes related to iron acquisition, melanin synthesis
      and cell defense were specially upregulated in the mouse model of infection. The
      upregulated transcripts of yeast cells during incubation with human blood were
      those predominantly related to cell wall remodeling/synthesis. The expression
      pattern of genes was independently confirmed in host conditions, revealing their
      potential role in the infection process. This work can facilitate functional
      studies of novel regulated genes that may be important for the survival and
      growth strategies of P. brasiliensis in humans.

PMID- 16962354
TI  - Functional analysis of mutations in TGIF associated with holoprosencephaly.
AB  - Holoprosencephaly (HPE) is the most common structural malformation of the
      forebrain and face in humans. Our current understanding of the pathogenesis of
      HPE attempts to integrate genetic susceptibility, evidenced by mutations in the
      known HPE genes, with the epigenetic influence of environmental factors.
      Mutations or deletions of the human TGIF gene have been associated with HPE in
      multiple population cohorts. Here we examine the functional effects of all
      previously reported mutations, and describe four additional variants. Of the
      eleven sequence variations in TGIF, all but four can be demonstrated to be
      functionally abnormal. In contrast, no potentially pathogenic sequence
      alterations were detected in the related gene TGIF2. These results provide
      further evidence of a role for TGIF in HPE and demonstrate the importance of
      functional analysis of putative disease-associated alleles.

PMID- 16962357
TI  - Eosinophils contribute to killing of adult Onchocerca ochengi within
      onchocercomata following elimination of Wolbachia.
AB  - Many filarial nematodes, including Onchocerca volvulus (the cause of human 'River
      Blindness'), have a mutually dependent relationship with Wolbachia bacteria.
      There has been much interest in Wolbachia as a chemotherapeutic target, since
      there are no macrofilaricidal drugs (i.e., lethal to adult worms) of low
      toxicity. Using the bovine parasite O. ochengi, we previously demonstrated that
      combined intensive and intermittent (COM) oxytetracycline treatment induces a
      sustained depletion of Wolbachia and is macrofilaricidal, whereas a short
      intensive regimen (SIR) is non-macrofilaricidal. To understand how targeting
      Wolbachia with oxytetracycline can lead to worm death, O. ochengi nodules
      (onchocercomata) were sequentially excised from cattle administered COM or SIR
      therapy, and cell infiltrates were microscopically quantified. Pre-treatment,
      worms were surrounded by neutrophils, with eosinophils rare or absent. At 8
      12weeks after either regimen, eosinophils increased around worms and were
      observed degranulating on the cuticle. However, with the SIR treatment,
      neutrophils returned to predominance by 48weeks, while in the COM group,
      eosinophilia persisted. These observations suggest that accumulation of
      degranulating eosinophils over a prolonged period is a cause rather than an
      effect of parasite death, and the macrofilaricidal mechanism of antibiotics may
      relate to facilitation of eosinophil infiltration around worms by ablation of
      Wolbachia-mediated neutrophilia.

PMID- 16962358
TI  - Molecular divergences of the Ornithodoros sonrai soft tick species, a vector of
      human relapsing fever in West Africa.
AB  - The soft tick Ornithodoros sonrai is recognized as the only vector of Borrelia
      crocidurae causing human relapsing fever in West Africa. Its determination has
      been exclusively based on morphological features, geographical distribution and
      vector competence. Some ambiguities persist in its systematics and may cause
      misunderstanding about West African human relapsing fevers epidemiology. By
      amplifying and aligning 16S and 18S rDNA genes in O. sonrai specimens collected
      from 14 distinct sites in Senegal and Mauritania, we showed the existence of four
      genetically different subgroups that were morphologically and ecologically
      identified as belonging to the same species. Within O. sonrai, intraspecific
      polymorphism was high (pairwise divergence from 0.2% to 16.4%). In all cases,
      these four subgroups formed a monophyletic clade sharing a common ancestor with
      East African soft ticks that transmit Borrelia duttoni human relapsing fever.
      From amplification of the flagellin gene of B. crocidurae we verified that all
      subgroups of O. sonrai were infected by B. crocidurae and may constitute vectors
      for this pathogen. All flagellin sequences were identical, refuting the
      hypothesis suggesting parallel evolution between O. sonrai and B. crocidurae.
      However, differences in infection rates were significant, suggesting different
      vector competences between subgroups of O. sonrai.

PMID- 16962359
TI  - Felid herpesvirus 1 glycoprotein G is a structural protein that mediates the
      binding of chemokines on the viral envelope.
AB  - Glycoprotein G (gG) orthologues have been described in several
      alphaherpesviruses. gG is expressed both as a membrane-anchored form on infected
      cells and as a secreted form. Recently, we reported that both forms of gG encoded
      by alphaherpesviruses infecting large herbivores and by Felid herpesvirus 1 (FeHV
      1) bind with high affinity to a broad range of CXC, CC and C-chemokines. Based on
      the viral species, gG has been reported either as a structural or a non
      structural protein. To date, the incorporation of FeHV-1 gG into virions has
      never been tested, nor the property of alphaherpesvirus structural gG to bind
      chemokines on the virion surface. In the present study, to address these
      questions, various FeHV-1 gG recombinant strains were produced using an original
      technique based on an infectious FeHV-1 BAC clone and restriction endonuclease
      mediated recombination. Using the recombinants produced, we were able to
      determine that FeHV-1 gG is a structural protein that acts as a chemokine-binding
      protein on the virion surface. In the light of these results, putative roles of
      gG in alphaherpesvirus infections are discussed, and an evolutionary scenario is
      proposed to explain the structural versus non-structural property of gG amongst
      alphaherpesviruses.

PMID- 16962360
TI  - A multivalent combination of experimental antituberculosis DNA vaccines based on
      Ag85B and regions of difference antigens.
AB  - Two candidate DNA vaccines based on the proteins CFP10 and CFP21 encoded by
      regions of difference (RDs) of Mycobacterium tuberculosis were evaluated
      individually and in multivalent combination with the immunodominant protein Ag85B
      for induction of protective immune responses against experimental tuberculosis.
      Experimental DNA vaccines induced substantial levels of cell-mediated immune
      responses as indicated by marked lymphocyte proliferation, significant release of
      the Th1 cytokines IFN-gamma and IL-12 (p40), and predominant cytotoxic T cell
      activity. High levels of antigen-specific IgG1 and IgG2a antibodies observed in
      the sera of immunized mice depicted strong humoral responses generated by DNA
      vaccine constructs. The multivalent combination of three DNA vaccine constructs
      induced maximal T cell and humoral immune responses. All the experimental
      vaccines imparted significant protection against challenge with M. tuberculosis
      H(37)Rv (in terms of colony-forming unit reduction in lungs and spleen) as
      compared to vector controls. The level of protection exhibited by multivalent DNA
      vaccine formulation was found to be equivalent to that of Mycobacterium bovis BCG
      observed both at 4 and 8 weeks post-challenge. These results show the protective
      potential of the multivalent DNA vaccine formulation used in this study.

PMID- 16962361
TI  - Clinical atovaquone-proguanil resistance of Plasmodium falciparum associated with
      cytochrome b codon 268 mutations.
AB  - Plasmodium falciparum resistance to atovaquone-proguanil has so far been
      associated with Y268S or Y268N mutations in cytochrome b, although these changes
      were identified in only seven of the 11 treatment failures. Here, we describe 10
      new cases of atovaquone-proguanil treatment failures among which the parasite
      resistance was confirmed in six cases, either by identifying correct plasma drug
      concentrations or by observing in vitro atovaquone resistance. Resistance was
      consistently associated with codon 268 mutations (Y268S or a previously
      unidentified mutation, Y268C). Notably, mutations were not detected before the
      treatment but only after the drug exposure.

PMID- 16962362
TI  - Finite element analysis of the penetrations of shear and normal vibrations into
      the soft tissues in a fingertip.
AB  - It is well accepted that the effects of mechanical vibration on the finger-hand
      arm system are strongly frequency-dependent: low frequency vibration can transmit
      from hand to arm, while high frequency vibration is absorbed in the local tissue
      of fingers. This assertion has not been validated directly. The purpose of the
      present study is to analyze the frequency- and deformation-dependent dynamic
      strains in the soft tissues in a fingertip that is subjected to vibration normal
      or tangential to the contact surface. The dynamic responses of the fingertip were
      analyzed using a multi-layered two-dimensional finite element model. The major
      anatomical substructures, i.e., skin, subcutaneous tissue, bone, and nail, are
      included in the model. The fingertip was found to have a major resonance around
      100-125 Hz and a second resonance around 250 Hz. The resonances of the fingertip
      are found to be independent of the direction of exposure (in normal or shear
      direction). The simulations further indicated that the dynamic strains induced by
      the vibration at low frequencies will penetrate deeper into the tissue (> 3 mm)
      while that at high frequencies will be concentrated in the superficial skin layer
      (< 0.8 mm). The model predictions are consistent with the published experimental
      observations.

PMID- 16962365
TI  - Insular pathology in Parkinson's disease patients with orthostatic hypotension.
AB  - Orthostatic hypotension (OH) in Parkinson's disease (PD) patients may be a
      significant source of morbidity and discomfort. Although peripheral ANS
      components have been associated with its development, central mechanisms are
      probably involved. The insular cortex is a central site of autonomic and limbic
      integration and neuropathologic studies have indicated its involvement in the
      neurodegenerative process of PD. To this end, we studied the neuropathology of
      the insular, temporal and parietal cortices in PD patients with and without OH.
      Our results suggest an association between the severity of PD-related
      neuropathology in the insular cortex and OH. Further research into the subject is
      warranted.

PMID- 16962366
TI  - Going back to Darwin's works.

PMID- 16962363
TI  - Stress-induced corneal epithelial apoptosis mediated by K+ channel activation.
AB  - One of the functional roles of the corneal epithelial layer is to protect the
      cornea, lens and other underlying ocular structures from damages caused by
      environmental insults. It is important for corneal epithelial cells to maintain
      this function by undergoing continuous renewal through a dynamic process of wound
      healing. Previous studies in corneal epithelial cells have provided substantial
      evidence showing that environmental insults, such as ultraviolet (UV) irradiation
      and other biohazards, can induce stress-related cellular responses resulting in
      apoptosis and thus interrupt the dynamic process of wound healing. We found that
      UV irradiation-induced apoptotic effects in corneal epithelial cells are started
      by the hyperactivation of K+ channels in the cell membrane resulting in a fast
      loss of intracellular K+ ions. Recent studies provide further evidence indicating
      that these complex responses in corneal epithelial cells are resulted from the
      activation of stress-related signaling pathways mediated by K+ channel activity.
      The effect of UV irradiation on corneal epithelial cell fate shares common
      signaling mechanisms involving the activation of intracellular responses that are
      often activated by the stimulation of various cytokines. One piece of evidence
      for making this distinction is that at early times UV irradiation activates a
      Kv3.4 channel in corneal epithelial cells to elicit activation of c-Jun N
      terminal kinase cascades and p53 activation leading to cell cycle arrest and
      apoptosis. The hypothetic model is that UV-induced potassium channel
      hyperactivity as an early event initiates fast cell shrinkages due to the loss of
      intracellular potassium, resulting in the activation of scaffolding protein
      kinases and cytoskeleton reorganizations. This review article presents important
      control mechanisms that determine Kv channel activity-mediated cellular responses
      in corneal epithelial cells, involving activation of stress-induced signaling
      pathways, arrests of cell cycle progression and/or induction of apoptosis.

PMID- 16962367
TI  - Combined genotoxic effects of radiation and a tobacco-specific nitrosamine in the
      lung of gpt delta transgenic mice.
AB  - It is important to evaluate the health effects of low-dose-rate or low-dose
      radiation in combination with chemicals as humans are exposed to a variety of
      chemical agents. Here, we examined combined genotoxic effects of low-dose-rate
      radiation and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), the most
      carcinogenic tobacco-specific nitrosamine, in the lung of gpt delta transgenic
      mice. In this mouse model, base substitutions and deletions can be separately
      analyzed by gpt and Spi- selections, respectively. Female gpt delta mice were
      either treated with gamma-irradiation alone at a dose rate of 0.5, 1.0 or 1.5
      mGy/h for 22 h/day for 31 days or combined with NNK treatments at a dose of 2
      mg/mouse/day, i.p. for four consecutive days in the middle course of irradiation.
      In the gpt selection, the NNK treatments enhanced the mutation frequencies (MFs)
      significantly, but no obvious combined effects of gamma-irradiation were
      observable at any given radiation dose. In contrast, NNK treatments appeared to
      suppress the Spi- large deletions. In the Spi- selection, the MFs of deletions
      more than 1 kb in size increased in a dose-dependent manner. When NNK treatments
      were combined, the dose-response curve became bell-shaped where the MF at the
      highest radiation dose decreased substantially. These results suggest that NNK
      treatments may elicit an adaptive response that eliminates cells bearing
      radiation-induced double-strand breaks in DNA. Possible mechanisms underlying the
      combined genotoxicity of radiation and NNK are discussed, and the importance of
      evaluation of combined genotoxicity of more than one agent is emphasized.

PMID- 16962364
TI  - Oxidative stress in glaucomatous neurodegeneration: mechanisms and consequences.
AB  - Reactive oxygen species (ROS) are generated as by-products of cellular
      metabolism, primarily in the mitochondria. Although ROS are essential
      participants in cell signaling and regulation, when their cellular production
      overwhelms the intrinsic antioxidant capacity, damage to cellular macromolecules
      such as DNA, proteins, and lipids ensues. Such a state of "oxidative stress" is
      thought to contribute to the pathogenesis of a number of neurodegenerative
      diseases. Growing evidence supports the involvement of oxidative stress as a
      common component of glaucomatous neurodegeneration in different subcellular
      compartments of retinal ganglion cells (RGCs). Besides the evidence of direct
      cytotoxic consequences leading to RGC death, it also seems highly possible that
      ROS are involved in signaling RGC death by acting as a second messenger and/or
      modulating protein function by redox modifications of downstream effectors
      through enzymatic oxidation of specific amino acid residues. Different studies
      provide cumulating evidence, which supports the association of ROS with different
      aspects of the neurodegenerative process. Oxidative protein modifications during
      glaucomatous neurodegeneration increase neuronal susceptibility to damage and
      also lead to glial dysfunction. Oxidative stress-induced dysfunction of glial
      cells may contribute to spreading neuronal damage by secondary degeneration.
      Oxidative stress also promotes the accumulation of advanced glycation end
      products in glaucomatous tissues. In addition, oxidative stress takes part in the
      activation of immune response during glaucomatous neurodegeneration, as ROS
      stimulate the antigen presenting ability of glial cells and also function as co
      stimulatory molecules during antigen presentation. By discussing current
      evidence, this review provides a broad perspective on cellular mechanisms and
      potential consequences of oxidative stress in glaucoma.

PMID- 16962368
TI  - Isolation and identification of non-chlorinated phenylbenzotriazole (non-ClPBTA)
      type mutagens in the Ho River in Shizuoka Prefecture, Japan.
AB  - We previously identified 2-[2-(acetylamino)-4-amino-5-methoxyphenyl]-5-amino-7
      bromo-4-chloro-2H-benzotriazole (PBTA) congeners as major mutagens in water
      concentrates from several rivers that flow in three different areas, i.e. Kyoto,
      Aichi, and Fukui Prefectures, in Japan. In synthesis studies, these PBTAs were
      shown to be formed from corresponding dinitrophenylazo dyes via non-chlorinated
      derivatives (non-ClPBTAs). However, only non-ClPBTA-1, i.e. 2-[2-(acetylamino)-4
      [bis(2-methoxyethyl)amino]-5-methoxyphenyl]-6-amino-4-bromo-2H-benzotriazole, had
      been detected as a minor contaminant in the Nishitakase River in Kyoto. In this
      study, analysis of mutagens in water concentrate from the Ho River, which flows
      through an area with a textile dyeing industry in Shizuoka Prefecture, Japan,
      allowed the isolation of four compounds (I, II, III, and IV). These four mutagens
      were identified as 2-[2-(acetylamino)-4-[N-(2-cyanoethyl)ethylamino]-5
      methoxyphenyl]-6-amino-4-bromo-2H-benzotriazole (non-ClPBTA-2), 2-[2
      (acetylamino)-4-[(2-hydroxyethyl)amino]-5-methoxyphenyl]-6-amino-4-bromo-2H
      benzotriazole (non-ClPBTA-3), 2-(2-acetylamino-4-amino-5-methoxyphenyl)-6-amino-4
      bromo-2H-benzotriazole (non-ClPBTA-4), and 2-[2-(acetylamino)-4-(diethylamino)-5
      methoxyphenyl]-6-amino-4-bromo-2H-benzotriazole (non-ClPBTA-7) by spectral data
      and co-chromatography using synthesized standards. Non-ClPBTA-3 and -7 were
      highly mutagenic in Salmonella typhimurium YG1024, inducing 159,000 and 178,000
      revertants/microg, respectively, in the presence of S9 mix. Like PBTAs, non
      ClPBTAs might have been produced from azo dyes during industrial processes in
      dyeing factories and released into rivers.

PMID- 16962369
TI  - Broad dissemination of Histomonas meleagridis determined by the detection of
      nucleic acid in different organs after experimental infection of turkeys and
      specified pathogen-free chickens using a mono-eukaryotic culture of the parasite.
AB  - Histomonas meleagridis, a flagellated protozoan parasite, is the causative agent
      of histomonosis (syn. histomoniasis, blackhead) in turkeys and chickens. The
      organs primarily affected by the parasite are the caeca and the liver. Until now,
      only few reports exist in which the parasite has been diagnosed in tissues other
      than those mentioned above. Hence, the aim of this study was to perform a
      systematic investigation of various organs of turkeys and specified pathogen-free
      chickens following an experimental infection with a mono-eukaryotic culture of
      Histomonas meleagridis in order to determine the dissemination of the flagellate
      in infected birds. Molecular methods like PCR and in situ hybridization were used
      for this purpose. For the first time, the DNA of the parasite could be detected
      in 13 different organs of infected turkeys by PCR including the proventriculus,
      duodenum, jejunum, caeca, pancreas, bursa of Fabricius, liver, kidney, spleen,
      heart, lung, thymus and the brain. Most of these findings were further confirmed
      by in situ hybridization. In contrast to the turkeys that all died shortly after
      the infection, all of the chickens survived without displaying any clinical
      symptoms. Even at necropsy, only mild pathological changes were observed in the
      caeca. Nevertheless, the parasite could also be detected in various organs of
      these birds, namely the caeca, bursa of Fabricius, kidney, heart and the brain.

PMID- 16962370
TI  - Gangliosides of the stroma layer participate in the interferon-gamma receptor
      dependent controls of myelopoiesis.
AB  - Stroma-mediated myelopoiesis depends upon growth-factors and an appropriate
      intercellular microenvironment, whose polarity is relevant for granulocyte
      macrophage colony stimulating factor (GM-CSF) mediated myeloid cell
      proliferation. Here we have studied qualitative and quantitative aspects of
      ganglioside participation in controls of the microenvironment required to sustain
      myelopoiesis. We analysed ganglioside synthesis, expression and shedding by two
      primary liver stromal cell cultures isolated from wild type and interferon-gamma
      (IFNgamma) receptor knockout mice. The latter one has a higher capacity to
      sustain myelopoiesis. FDC-P1 myeloid growth factor-dependent cell line was used
      as the reporter system, monitoring the cell survival and proliferation that
      reflect the bio-availability and the activity of GM-CSF. Although the two stromal
      cells synthesised the same gangliosides their relative content was quite
      different. FDC-P1 proliferation decreased in cultures in which ganglioside
      synthesis was inhibited in the stroma, as well as in presence of stroma cell
      supernatants in which GM3 was neutralised by the anti-GM3 monoclonal antibody.
      Addition of exogenous GM3 reverted the inhibition and sustained proliferation of
      FDC-P1 cells. FDC-P1 cells do not accumulate GM3, but they are able to take up
      the stroma-produced sphingolipids. Thus, stroma has a double role in sustaining
      myelopoiesis, providing both growth factor(s) and ganglioside(s) required for the
      optimal stimulation of the myeloid cell proliferation, and the IFNgamma mediated
      stroma-dependent controls of myelopoiesis are determinant for this cell
      interaction.

PMID- 16962371
TI  - The proinflammatory mediator Platelet Activating Factor is an effective substrate
      for human group X secreted phospholipase A2.
AB  - Platelet Activating Factor (PAF) is a potent mediator of inflammation whose
      biological activity depends on the acetyl group esterified at the sn-2 position
      of the molecule. PAF-acetylhydrolase (PAF-AH), a secreted calcium-independent
      phospholipase A(2), is known to inactivate PAF by formation of lyso-PAF and
      acetate. However, PAF-AH deficient patients are not susceptible to the biological
      effects of inhaled PAF in airway inflammation, suggesting that other enzymes may
      regulate extracellular levels of PAF. We therefore examined the hydrolytic
      activity of the recently described human group X secreted phospholipase A(2) (hGX
      sPLA(2)) towards PAF. Among different sPLA(2)s, hGX sPLA(2) has the highest
      affinity towards phosphatidylcholine (PC), the major phospholipid of cellular
      membranes and plasma lipoproteins. Our results show that unlike group IIA, group
      V, and the pancreatic group IB sPLA(2), recombinant hGX sPLA(2) can efficiently
      hydrolyze PAF. The hydrolysis of PAF by hGX sPLA(2) rises abruptly when the
      concentration of PAF passes through its critical micelle concentration suggesting
      that the enzyme undergoes interfacial binding and activation to PAF. In
      conclusion, our study shows that hGX sPLA(2) may be a novel player in PAF
      regulation during inflammatory processes.

PMID- 16962372
TI  - Bioaffinity-based an inexpensive and high yield procedure for the immobilization
      of turnip (Brassica rapa) peroxidase.
AB  - This study demonstrates the immobilization of carbohydrate containing turnip
      peroxidase on an inexpensive bioaffinity adsorbent, Concanavalin A-cellulose
      support. The bioaffinity support was prepared simply by incubating cellulose
      powder with jack bean extract at 4 degrees C. Cellulose powder adsorbed 30 mg
      concanavalin A/g of the matrix. Concanavalin A adsorbed cellulose has been
      employed for the simultaneous purification and immobilization of glycoenzymes
      directly from ammonium sulphate fractionated proteins of turnip. The obtained
      bioaffinity support was quite effective in high yield immobilization of
      peroxidase from turnip and it retained 672 U/g. Turnip peroxidase immobilized on
      concanavalin A-cellulose support retained 80% of the initial activity.
      Immobilized turnip peroxidase preparation was quite resistant against the
      denaturation mediated by pH, heat, urea, guanidinium-HCl, Surf Excel,
      cetyltrimethylammonium bromide and water-miscible organic solvents; dimethyl
      formamide, dioxane and n-propanol. Low concentration of detergents like Surf
      Excel and cetyltrimethylammonium bromide enhanced the activity of soluble and
      immobilized turnip peroxidase.

PMID- 16962373
TI  - Hope in parents of adolescents with cancer--factors endangering and engendering
      parental hope.
AB  - The purpose of the study was to describe hope in parents of adolescents with
      cancer. The data were collected by interviewing nine parents of six families
      (n=18) and analysed by inductive content analysis. Parents' hope implies an
      orientation towards life and the future, trust, togetherness and wishes. Hope is
      associated with suffering and despair and it is a life-promoting factor. Factors
      associated with parental hope relate to the adolescent, the adolescent's cancer
      and health status, the care received and the care-giving personnel, continuation
      of life, the parent him- or herself, economics, other people, faith and pets. The
      findings confirm the statement that hope appears to be central to parents having
      a child with cancer. The factors endangering and engendering hope are related to
      several dimensions of family life, suggesting that hope is a broad,
      multidimensional phenomenon. Engendering hope is important in nursing: hope is a
      life-sustaining factor, which helps the person to cope in difficult life
      situations. In caring for an adolescent with cancer and his or her parents, it is
      of utmost importance to minimize factors endangering parental hope and to foster
      factors that engender parental hope.

PMID- 16962374
TI  - PEDF: a potential molecular therapeutic target with multiple anti-cancer
      activities.
AB  - Pigment epithelium-derived factor (PEDF) is an endogenously produced protein that
      is widely expressed throughout the human body, and exhibits multiple and varied
      biological activities. Already established as a potent anti-angiogenic molecule,
      PEDF has recently shown promise as a potential anti-tumour agent, causing both
      direct and indirect tumour suppression. Here, we explore the unique anti-tumour
      properties of PEDF and discuss its role as an effective anti-angiogenic, anti
      proliferative and pro-differentiation factor. We also discuss the prospects for
      PEDF therapy and the need for a closer evaluation of issues such as delivery,
      stability and potential toxicity.

PMID- 16962375
TI  - MHC-peptide specificity and T-cell epitope mapping: where immunotherapy starts.
AB  - The evaluation and characterization of epitope-specific human leukocyte antigen
      (HLA)-restricted memory T-cell reactivity is an important step for the
      development of preventive vaccines and peptide-based immunotherapies for viral
      and tumor diseases. The past decade has witnessed the use of HLA-restricted
      peptides as tools to activate strong immune responses of naive or memory T cells
      specifically. This has fuelled an active search for methodological approaches
      focusing on HLA and peptide associations. Here, we outline new perspective on the
      emerging opportunity of evaluating HLA and peptide restriction by using novel
      approaches, such as quantitative real-time PCR, that can identify epitope
      specificities that are potentially useful in clinical settings.

PMID- 16962376
TI  - From barriers to bridges: chondroitin sulfate proteoglycans in neuropathology.
AB  - Emerging studies have revealed new roles for the neural extracellular matrix in
      neuropathologies. The structure of this matrix is unusual and uniquely enriched
      in chondroitin sulfate proteoglycans, particularly those of the lectican family.
      Historically, lecticans have attracted considerable interest in the normal and
      injured brain for their prominent roles as inhibitors of cellular motility,
      neurite extension and synaptic plasticity. However, these molecules are
      structurally heterogeneous, have distinct expression patterns and mediate unique
      interactions, suggesting that they might have other functions in addition to
      their traditional role as chemorepulsants. Here, we review recent work
      demonstrating unique modifications and structural microheterogeneity of the
      lecticans in the diseased CNS, which might relate to novel roles of these
      molecules in neuropathologies.

PMID- 16962377
TI  - Echocardiographic right ventricular strain analysis in chronic heart failure.
AB  - OBJECTIVE: We sought to compare the additive value of right ventricular (RV)
      function assessed by longitudinal systolic strain (epsilon% - ROI: 9.2 at 10.8
      mm) with cardiopulmonary exercise testing (CPET) or brain natriuretic peptide
      (BNP) in patients with heart failure (HF). METHOD: We studied 19-patients (age =
      56 +/- 8 years) in New York Heart Association HF class III-IV, who underwent
      standard and tissue Doppler echocardiography, CPET and BNP measurements on the
      same day. RV function was assessed by systolic strain (epsilon, %, ROI: 9.2-10.8
      mm) in the mid-segment. Clinical outcomes were examined at 6 months. RESULTS:
      epsilon (-19.9+/-6.8%) was correlated with BNP (R = 0.52, P = 0.02), slope
      VE/VCO(2) (R = -0.65, P = 0.003), peak VO(2) (R = 0.46, P = 0.04) and the maximal
      workload (Watts) developed during CPET (R = 0.54, P=0.02). During follow-up, 1
      patient died, 1-underwent heart transplantation, and 4 were re-hospitalized for
      worsening HF. Patients with major adverse cardiac events (MACE) had a
      significantly higher mean BNP concentration (852.8 ng/mL +/- 1114.3 vs. 201.4+ /-
      293.8, P = 0.03), higher VE/VCO(2) (41.3 +/- 3.6 vs. 35.0 +/- 4.8 P < 0.001) and
      lower epsilon (-13.9 +/- 4.9 vs. -22.2+ /- 5.8, P < 0.001) than patients who
      remained MACE-free. By multivariate analysis, ST was the only predictor of MACE.
      CONCLUSION: In HF-patients presenting, RV-function assessed by systolic epsilon
      was reliable, easily measurable and a stronger prognosticator than CPET or BNP.

PMID- 16962378
TI  - Acquired pulmonary artery branch stenosis caused by pulmonary thromboembolism.
AB  - We present a case of acquired pulmonary artery branch stenosis caused by
      pulmonary thromboembolism. The patient presented with symptoms mimicking aortic
      dissection. An emergent transesophageal echocardiogram showed a high gradient
      across the right pulmonary artery along with mobile thrombi. The vital importance
      making an accurate diagnosis and ruling out aortic dissection is emphasized in
      view of the need for urgent heparinization or thrombolysis for pulmonary
      thromboembolism as this is contraindicated in aortic dissection.

PMID- 16962379
TI  - Papillary fibroelastoma of the aortic valve: a rare cause of stroke.
AB  - We report a case of a 59-year-old woman with recurrent cerebrovascular insults
      caused by a papillary fibroelastoma of the aortic valve. Primary cardiac tumors
      are rare. Papillary fibroelastoma (PFE) is the most common valvular tumor and the
      second cardiac benign tumor after myxoma. The clinical presentation of PFE varies
      from asymptomatic to severe embolic complications. The tumor was surgically
      removed to avoid new embolic events.

PMID- 16962380
TI  - Efficacy, safety, and tolerability of oxcarbazepine monotherapy.
AB  - OBJECTIVE: This prospective, open-label, multicenter study evaluated the efficacy
      and tolerability of oxcarbazepine as monotherapy in patients with partial
      seizures who switched from their current antiepileptic drug (AED) monotherapy
      because of lack of efficacy or poor tolerability. METHOD: Patients (>or=12 years
      old) experiencing 2-40 seizures per month while receiving an AED were included.
      During a 16-week treatment phase, oxcarbazepine was initiated (8-10mg/kg for
      children; 600 mg/day for adults) and titrated up over 4 weeks while the existing
      AED was tapered off. Improvement in seizure frequency (defined as >or=50%
      reduction compared with baseline) was evaluated for all patients, as well as the
      subgroups of patients switched due to poor tolerability or lack of efficacy.
      RESULTS: Overall, 52% of patients experienced a 50% reduction in seizure
      frequency, 35% had a >or=75% reduction, and 18% were seizure-free. The most
      frequent (>10%) adverse events were dizziness, nausea, headache, somnolence, and
      fatigue. Overall, 17% of patients prematurely withdrew because of an adverse
      event; 62% of these withdrawals occurred during the conversion period.
      CONCLUSION: Oxcarbazepine as monotherapy may be a favorable treatment option for
      patients with partial seizures or poor tolerability of their existing monotherapy
      regimen.

PMID- 16962381
TI  - Robust analysis of biomarker data with informative missingness using a two-stage
      hypothesis test in an HIV treatment interruption trial: AIEDRP AIN503/ACTG A5217.
AB  - Clinical trial AIN503/A5217 investigates whether a period of early treatment with
      antiretroviral therapy might lower the viral setpoint in subjects recently
      infected with HIV-1. We consider two statistical issues. First, even under the
      null hypothesis control arm subjects are more likely than treatment arm subjects
      to be missing final outcome data because of disease progression. The analysis
      must adjust for this missing data, or it may be unacceptably biased. Second,
      comparing outcomes between treatment and control arms at identical times post
      randomization gives different information than comparing outcomes at the same
      amount of time off-therapy, as measured post-randomization. This may make
      interpretation of results problematic. We formulate the null hypothesis of the
      study as exchangeability under a time-shift between arms, which we call "time
      delay" between the study arms. This captures clinically relevant information, and
      allows us to formalize a two-stage hypothesis test in which stage one is a
      comparison between arms at identical times post-randomization, and stage two is a
      comparison between arms at identical times off-therapy, as measured post
      randomization. Importantly, within this framework we can show that the two-stage
      test can be adjusted for the missing data using a simple worst-rank substitution.

PMID- 16962382
TI  - African Americans and participation in clinical trials: differences in beliefs
      and attitudes by gender.
AB  - OBJECTIVES: To explore gender differences in perceptions of 1) barriers and
      motivators to participation in clinical trials and perceived need of clinical
      trials and 2) perceptions of risks and benefits of participation in clinical
      trials in African American men and women. METHODS: Focus groups were conducted
      among African American participants by gender. A total of 67 African American
      participated in the focus groups. All focus groups were audio-taped and
      transcribed verbatim. Data analysis was performed by combining the key elements
      of grounded theory and content analysis with the assistance of the qualitative
      software ATLAS.ti 5.0. RESULTS: Different themes emerged for men versus women.
      The business and economic of research were important to male participants. The
      researcher-participant relationship emerged as one of the strongest themes
      related to potential female participation in research. DISCUSSION: Focus group
      results indicate that African American men and women present different
      preferences, beliefs and barriers to participation. Men expressed the desire to
      know information on funding issues, financial benefit and impact of the research.
      Women expressed the desire to be treated respectfully and as an individual as
      opposed to just a study subject. Integrating gender preferences into researcher
      participant interactions, advertisement, informed consent delivery and
      advertisement of research studies may lead to increased participation rates.
      Discussing and presenting relevant information on clinical research funding
      mechanisms, and the business of clinical research with potential participants may
      be helpful in building trust with the researcher and the research team. Creating
      a process for information exchange and methods to minimize the power imbalance
      between the researcher and participant may also build trust and help participants
      feel more comfortable to participate in research.

PMID- 16962383
TI  - Gastrointestinal disturbances in eating disorders: clinical and neurobiological
      aspects.
AB  - Symptoms of the upper and lower gastrointestinal (gastrointestinal) tract have
      been described in anorexia nervosa and bulimia nervosa. Studies focusing on
      general outcome and medical comorbidity describe a worse outcome in the binge
      eating/purging subtype of anorexia nervosa compared to the restricting subtype.
      Both anorexia nervosa subtypes experience substantial delays in gastric emptying
      as well as constipation. These gastrointestinal disturbances may play a role in
      anorexia nervosa patients' difficulties with refeeding and weight restoration.
      Bulimia nervosa patients showed increased gastric emptying capacity, with delayed
      gastric emptying and diminished gastric relaxation. In addition, diminished
      release of cholecystokinin and abnormalities in enteric autonomic function were
      found in bulimia nervosa patients. These factors may play a role in the
      perpetuation of the disease. Gastrointestinal disturbances develop secondary to
      the disordered eating behaviour and the concomitant malnutrition and subside
      mostly with the resumption of normal food intake and body weight. Knowledge of
      these changes may be of critical importance in avoiding misdiagnosis and
      successful therapy.

PMID- 16962384
TI  - Passenger well-being in airplanes.
AB  - Passenger well-being is influenced by cabin environmental conditions which
      interact with individual passenger characteristics like age and health
      conditions. Cabin environment is composed of different aspects, some of which
      have a direct influence on gastrointestinal functions and may directly generate
      nausea, such as cabin pressure, oxygen saturation, and motion or vibration. For
      example, it has been shown that available cabin pressure during normal flight
      altitude can significantly inhibit gastric emptying and induce dyspepsia-like
      symptoms when associated with a fibre-rich meal. Other aspects of the cabin
      environment such as space and variability of seating, air quality, and noise,
      also have been shown to modulate (reduce or increase) discomfort and nausea
      during flights. Individual passenger characteristics and health status also have
      been demonstrated to increase vulnerability to adverse health outcomes and
      discomfort.

PMID- 16962385
TI  - Expression of Ndufb11 encoding the neuronal protein 15.6 during neurite outgrowth
      and development.
AB  - Neurite outgrowth (e.g. axonal or dendrite outgrowth) of neurons is necessary for
      the development and functioning of the central nervous system. It is well
      accepted that the differentiation of neurons and neurite outgrowth involve
      alterations in gene expression. Furthermore, mitochondria play a role in
      different aspects of neurite outgrowth. Here we show that the expression of
      Ndufb11, a gene encoding the mitochondrial protein NP15.6 is decreased in the
      course of neuronal differentiation. NP15.6 is homologous to the bovine protein
      ESSS, a component of the mitochondrial complex 1. The homologous human NDUFB11
      gene is localized to Xp11.3-Xp11.23, a region associated with neurogenetic
      disorders. The down-regulation of NP15.6 correlates with neurite outgrowth of
      PC12 cells induced by nerve growth factor. Furthermore, we analyzed the
      expression of Ndufb11 in the embryonic and adult mouse.

PMID- 16962386
TI  - Tissue, cellular and sub-cellular localization of the Vangl2 protein during
      embryonic development: effect of the Lp mutation.
AB  - Loop-tail (Lp) mice show a very severe neural tube defect, craniorachischisis,
      which is caused by mis-sense mutations in the Vangl2 gene. The membrane protein
      Vangl2 belongs to a highly conserved group of proteins that regulate planar
      polarity in certain epithelia, and that are also important for convergent
      extension movements during gastrulation and neurulation. A specific anti-Vangl2
      antiserum was produced and used to examine the tissue, cell type, and sub
      cellular localization of Vangl2 during embryogenesis. Vangl2 protein is expressed
      at high levels in the neural tube and shows a dynamic expression profile during
      neurulation. After neural tube closure, robust Vangl2 staining is detected in
      several neural and neurosensory tissues, including cerebral cortex, dorsal root
      ganglia, olfactory epithelium, retina, mechanosensory hair cells of the cochlea,
      and optic nerve. Vangl2 is also expressed during organogenesis in a number of
      tubular epithelia, including the bronchial tree, intestinal crypt/villus axis,
      and renal tubular segments derived from ureteric bud and from metanephric
      mesenchyme. Examination of Vangl2 localization in the neural tubes and cochleas
      of the normal and Lp/Lp embryos shows disruption of normal membrane localization
      of Vangl2 in independent alleles at Lp (Lp, Lp(m1Jus)) as well as overall
      decrease in the expression level.

PMID- 16962387
TI  - Electrochemical detection of E. coli 16S rDNA sequence using air-plasma-activated
      fullerene-impregnated screen printed electrodes.
AB  - A new DNA modified electrode for the electrochemical detection of 16S rDNA
      extracted from Escherichia coli (JCM1649) is proposed. The electrodes were
      fabricated by screen printing a fullerene-impregnated carbon ink onto a
      poly(methylmethacrylate) substrate and immobilizing a probe DNA on the surface
      after activating the electrode with air plasma. The results indicated a dramatic
      improvement in the surface coverage of the immobilized probe DNA, and of the
      reduction peak of the redox indicator (Co(phen)(3)(3+)) due to the incorporation
      of fullerene. By immobilizing the probe onto the fullerene-impregnated screen
      printed electrodes, the PCR product of the 16S rDNA extracted from E. coli was
      directly detected without any pretreatment. A well defined signal difference was
      observed between the perfectly matching oligonucleotide and the mismatching one,
      and it was possible to detect the target at the modified electrode. This method
      enabled us to clearly detect the two base mismatches in the ca. 1500-bases long
      16S rDNA sequence.

PMID- 16962388
TI  - The structure of the second cytosolic loop of the yeast mitochondrial ADP/ATP
      carrier AAC2 is dependent on the conformational state.
AB  - To detect structural changes in the second cytosolic loop of the mitochondrial
      ADP/ATP carrier of Saccharomyces cerevisiae AAC2, we prepared 20 single cysteine
      mutants by replacing each amino acid in the S213 to L232 region. All single
      cysteine mutants were fully functional, because they could restore growth on
      glycerol of a yeast strain lacking functional ADP/ATP carriers. First, these
      single-Cys mutants were treated with carboxyatractyloside to lock the carrier in
      the cytosolic state or with bongkrekic acid to generate the matrix state, and
      then with the membrane-impermeable SH reagent eosin-5-maleimide (EMA) to probe
      accessibility. The amino acid residues S213C, L214C, F231C and L232C were not
      labeled, indicating that these 4 residues must have been buried in the membrane,
      whereas the region between residues K215 and S230 is accessible to labeling and
      must, therefore, have protruded into the aqueous phase. Residue L218C showed
      strong resistance against EMA labeling regardless of the state of the carrier,
      but the reason for such behavior is unclear. On the contrary, the labeling of the
      residues between F227C and S230C was strongly dependent on the state of the
      carrier. Thus, the C-terminal region of the second cytosolic loop in AAC2 changes
      its environment when the carrier cycles between the matrix and cytosolic state.

PMID- 16962389
TI  - High performance liquid chromatography-electrospray ionization mass spectrometric
      determination of isosorbide 5-mononitrate in human plasma.
AB  - A novel, selective and sensitive high performance liquid chromatography-mass
      spectrometric (HPLC-MS) method has been developed for the determination of
      isosorbide 5-mononitrate (5-ISMN) in human plasma. With acetaminophen as internal
      standard, sample pretreatment involved one-step extraction with diethyl ether of
      0.5 mL plasma. Analysis was performed on an ACQUITY UPLC BEH C(18) column (100 mm
      x 2.1mm, 1.7 microm) with mobile phase consisting of acetonitrile-water (20:80,
      v/v). The detection was carried out by means of electrospray ionization mass
      spectrometry in negative ion mode with selected ion recording (SIR). Standard
      curves were linear (r(2)> or =0.99) over the concentration range of 1.04-1040
      ng/mL. The lower limit of quantification (LLOQ) was 1.04 ng/mL. The intra- and
      inter-day precisions (RSDs) were less than 8.6% and 13.4%, respectively, and the
      accuracy (RE) was within +/-0.45%. The method herein described was fully
      validated and successfully applied to the pharmacokinetic study of 5-ISMN in
      compound extended-release tablets in 18 healthy male volunteers after oral
      administration.

PMID- 16962390
TI  - Determination of tropisetron in human plasma by high performance liquid
      chromatographic method with UV detection and its application to a bioequivalence
      study.
AB  - A simple and sensitive high performance liquid chromatography method with UV
      detection was described for the determination of tropisetron in human plasma. The
      prepared sample solution was injected onto BDS-C(8) reversed column using a
      mixture of ammonium acetate (100 mM, PH adjusted to 4.3 with glacial acetic acid)
      and acetonitrile (80:20, v/v) as mobile phase. The wavelength of UV detector was
      set at 285 nm. No interference from any endogenous substances was observed during
      the elution of tropisetron and internal standard (ondansetron hydrochloride). The
      lower limit of quantification was evaluated to be 1 ng/mL. The method was used in
      a randomized crossover bioequivalence study of two different tropisetron
      preparations in 20 healthy volunteers.

PMID- 16962391
TI  - Quantification of serine enantiomers in rat brain microdialysate using Marfey's
      reagent and LC/MS/MS.
AB  - The ability to selectively measure serine enantiomer concentrations in rat brain
      microdialysate is essential during drug discovery to study the interaction of d
      serine with the N-methyl-d-aspartate (NMDA) subtype of the glutamate receptor.
      NMDA receptor-stimulating agents, such as d-serine, have been shown to reduce the
      negative symptoms and cognitive dysfunction in individuals with schizophrenia
      when added to conventional or atypical antipsychotic drug regimens. In the work
      presented here, an LC/MS/MS assay was developed and validated to simultaneously
      measure d-serine and l-serine concentrations in rat brain microdialysate. Reverse
      phase chromatographic resolution of the enantiomers was obtained through
      derivatization with 1-fluoro-2,4-dinitrophenyl-5-l-alanine amide (Marfey's
      reagent). The assay was validated to determine concentrations over the range of
      10-7500 ng/mL using electrospray ionization and multiple reaction monitoring
      (MRM). Both intra- and inter-day precision and accuracy were less than 16.5% (RE)
      and 7% (CV) for both analytes, respectively, and assay throughput was increased
      significantly relative to existing methodologies.

PMID- 16962392
TI  - Centrifugal partition chromatography as a tool for preparative purification of
      pea albumin with enhanced yields.
AB  - A new procedure including the use of centrifugal partition chromatography (CPC)
      is proposed to purify PA1b and its isoforms. These pea (Pisum sativum L.) seed
      proteins are toxic against weevils and can be used as an environment-friendly
      insecticide. CPC was applied to a whole albumin fraction prepared from pea flour.
      The butanol:aqueous TFA system used in CPC allowed the separation of PA1b from
      other albumins and a degree of purification above 95%. Compared to analytical
      procedures based on methanol extraction, anion exchange and then reversed-phase
      chromatography (RPC), CPC recovered PA1b in much better yield, which is
      indispensable for large-scale purification of a biodegradable insecticide.

PMID- 16962393
TI  - Chiral separation of Frovatriptan isomers by HPLC using amylose based chiral
      stationary phase.
AB  - A stereospecific HPLC method for separation of Frovatriptan enantiomers in bulk
      drug and pharmaceutical formulations was developed and validated on a normal
      phase amylose derivertized chiral column. The effects of the organic modifiers
      namely 2-propanol, ethanol and diethyl amine (DEA) in the mobile phase were
      optimized to obtain the best enantiomeric separation. Calibration curves were
      linear over the range of 200-6150 ng/mL, with a regression coefficient (R(2)) of
      0.9998. The limit of detection (LOD) and limit of quantification (LOQ) were 65
      ng/mL and 200 ng/mL, respectively. The method was accurate and precise and
      suitable for the intended purpose. Analysis results were compared with the
      results obtained by using a validated chiral CE method and found to be in very
      good agreement. This method can be successfully applied to the enantiomeric
      purity analysis of Frovatriptan in pharmaceutical bulk drug samples and
      formulations.

PMID- 16962394
TI  - Simultaneous determination of AMN107 and Imatinib (Gleevec, Glivec, STI571) in
      cultured tumour cells using an isocratic high-performance liquid chromatography
      procedure with UV detection.
AB  - A reversed phase high-performance liquid chromatographic (HPLC) method with UV
      detection was developed for the simultaneous determination of imatinib (Gleevec,
      Glivec, STI571) and AMN107 in cultured tumour cells, using clozapine as an
      internal standard. The compounds of interest were extracted by liquid-liquid
      extraction using TOXI-TUBES((R)) A extraction tubes. Chromatographic separation
      was performed on a Phenomenex Gemini C18 reversed phase column (150 mm x 2.0 mm,
      5 microm particle size), using a mixture of 65% CH(3)OH (methanol) and 35%
      NH(4)Ac (Ammonium acetate) buffer (20mM, pH 10). Separation was achieved under
      isocratic conditions at a flow rate of 0.5 ml/min. Imatinib, clozapine and AMN107
      are detected by UV detection at 260 nm. Calibration curves were linear from 50 to
      7500 ng/ml with correlation coefficients (r(2)) better than 0.998. The limit of
      quantitation (LOD) was 50 ng/ml. The method has been successfully applied to a
      cellular kinetics study.

PMID- 16962395
TI  - Determination of gambogic acid in human plasma by liquid chromatography
      atmospheric pressure chemical ionization-mass spectrometry.
AB  - A high-performance liquid chromatography-atmospheric pressure chemical ionization
      mass spectrometry (HPLC-APCI-MS) method was established for the determination of
      gambogic acid (GA) in human plasma using ursolic acid as the internal standard
      (I.S.). Plasma samples were extracted with ethyl acetate and separated on a
      Hanbon Lichrospher 5-C18 column with a mobile phase of acetonitrile
      tetrahydrofuran-water (70:23:7, v/v). Gambogic acid was determined by using
      atmospheric pressure chemical ionization (APCI) in a single quadrupole mass
      spectrometer. HPLC-APCI-MS was performed in the selected ion monitoring (SIM)
      mode using target ions at [M-H](-)m/z 627.4 for gambogic acid and [M-H](-)m/z
      455.4 for the I.S. Calibration curve was linear over the range of 3.108-4144
      microg/L. The lower limit of quantification was 3.108 microg/L. The intra- and
      inter-run precisions were less than 12.3 and 14.1%, respectively. The method has
      been successfully applied to study the pharmacokinetics of gambogic acid in
      patients with malignant tumour.

PMID- 16962396
TI  - An improved method for haptoglobin 1-1, 2-1, and 2-2 purification using
      monoclonal antibody affinity chromatography in the presence of sodium dodecyl
      sulfate.
AB  - Human haptoglobin (Hp) is classified as three phenotypes: Hp 1-1, 2-1, and 2-2.
      Previously, we had isolated this protein by affinity columns using either
      hemoglobin or monoclonal antibody (mAb) prepared against Hp beta-chain (clone 8B1
      3A). The isolated Hp from both methods, however, contaminates plasma
      apolipoprotein A-I (apoA-I). In the present report, we have developed a novel
      affinity column procedure using an mAb prepared against alpha-chain of Hp (clone
      3H8) for Hp purification. Plasma was first chromatographed onto the column
      followed by a normal wash with a buffer containing 0.12 M NaCl and 0.02 M
      phosphate, pH 7.4 (PBS). The bound proteins were then prewashed with a 0.04%
      sodium dodecyl sulfate (SDS)-PBS, pH 7.4, to remove the low-affinity bound apoA-I
      from Hp. Finally, the bound Hp was eluted with a 0.1% SDS-PBS, pH 11, and
      collected in tubes containing 1 M Tris-HCl, pH 6.8. As a result, the isolated Hp
      was devoid of apoA-I and was able to retain the biological function by forming an
      Hp-hemoglobin complex. The homogeneity of each isolated Hp 1-1, 2-1, or 2-2 was
      greater than 95% with an yield greater than 50%. The procedure described here is
      significantly improved in time consumption, recovery, and purity. The rationale,
      design, and optimization for each step are described in detail.

PMID- 16962397
TI  - Sensitive quantification of diphemanil methyl sulphate in human plasma by liquid
      chromatography-tandem mass spectrometry.
AB  - A simple detection system with a high-performance liquid chromatography (HPLC)
      with positive ionisation-tandem mass spectrometry (ESI-MS/MS) for determining
      diphemanil methylsulphate (DMS) levels in human plasma using 4
      diphemanylmethylene,1-methylpiperidine as an internal standard (I.S.), is
      proposed. The acquisition was performed with the multiple reactional monitoring
      (MRM) mode, by monitoring the transitions: m/z 278>262 for DMS and m/z 263>247
      for the I.S. The method involved a simple single-step deproteinisation with
      acetonitrile. The analyte was chromatographed on a Zorbax C18 reversed-phase
      chromatographic column by isocratic elution with 10(-3)M ammonium acetate and 10(
      3)M hexafluorobutyric acid, adjusted to pH 7.0 with ammoniac/acetonitrile (40/60,
      v/v). The results were linear over the studied range (0.5-50.0 ng mL(-1)) and the
      total analysis time for each run was 10 min. The mean extraction apparent
      recoveries expressed at the 95% intervals of confidence were 94-104% for DMS and
      92-106% for the I.S. The intra- and inter-assay precisions were 4.6-8.4% and 2.9
      10.6%, respectively. The limit of quantification was 0.15 ng mL(-1). The devised
      assay was successfully applied to the residual concentrations monitoring in
      infant.

PMID- 16962398
TI  - Simultaneous determination of ribavirin and ribavirin base in monkey plasma by
      high performance liquid chromatography with tandem mass spectrometry.
AB  - For the first time, a liquid chromatographic method with tandem mass
      spectrometric detection (LC-MS/MS) for the simultaneous determination of
      ribavirin and rabavirin base was developed and validated over the concentration
      range of 10-5,000 ng/ml, respectively, using a 0.025 ml monkey plasma sample.
      Ribavirin, ribavirin base, and the internal standards were extracted from monkey
      plasma via protein precipitation. After evaporation of the supernatant, the
      extract was reconstituted with 5% methanol (containing 0.1% formic acid) and
      injected onto the LC-MS/MS system. Optimum chromatographic separation was
      achieved on a Waters Atlantis dc18 (150 mm x 2.1mm, 5 microm) column with mobile
      phase run in gradient with 100% water containing 0.5% formic acid (A) and 90%
      acetonitrile (containing 0.5% formic acid (B). The flow rate was 0.4-0.6 ml/min
      with total cycle time of approximately 7.0 min. Post-column addition of
      acetonitrile (containing 0.1% formic acid) at 0.3 ml/min was used to increase the
      ionization efficiency in the MS source. The method was validated for sensitivity,
      linearity, reproducibility, stability and recovery. Lack of adverse matrix effect
      and carry-over was also demonstrated. The intra-day and inter-day precision and
      accuracy of the quality control (QC) samples were <9.0% relative standard
      deviation (R.S.D.) and 10.8% bias for ribavirin, and 10.3% R.S.D. and 11.3% bias
      for ribavirin base. The current specific, accurate and precise assay is useful in
      support of the toxicokinetic and pharmacokinetic studies of these compounds.

PMID- 16962399
TI  - Development of the fingerprints for the quality of the roots of Salvia
      miltiorrhiza and its related preparations by HPLC-DAD and LC-MS(n).
AB  - High-performance liquid chromatographic (HPLC) fingerprints were developed for
      identification of both lipophilic and hydrophilic components of the roots of
      Salvia miltiorrhiza and four related preparations. These samples were separated
      with an Agilent Zorbax Extend C(18) reserved-phase column (5 microm, 250 mm x 4.6
      mm) by linear gradient elution using water-phosphoric acid (100:0.026, v/v) and
      acetonitrile as mobile phase. The flow rate was 0.8 ml/min and the detector
      wavelength was set at 280 nm. Mean chromatograms and correlation coefficients of
      samples were calculated by the software "Similarity Evaluation System for
      Chromatographic Fingerprint of TCM". The correlation coefficients of Danshen and
      Fufang Danshen tablets (FDT) samples were in the range of 0.352-0.993 and 0.768
      0.987, respectively. The correlation coefficients of Compound Danshen dripping
      pills (CDDP), Danshen injection (DSI) and Xiangdan injection (XDI) samples were
      higher than 0.928, 0.850 and 0.960, respectively. It was the first time to
      identify 34 peaks by comparing with standard compounds and using liquid
      chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS(n))
      technique. All results indicated that the developed fingerprint assay could be
      readily utilized as a quality control method for S. miltiorrhiza and its related
      preparations.

PMID- 16962400
TI  - 1Alpha,25-dihydroxy-2beta(3-hydroxypropoxy)vitamin D3 (ED-71) suppressed callus
      remodeling but did not interfere with fracture healing in rat femora.
AB  - INTRODUCTION: Because osteoporotic patients are prone to fractures, it must be
      considered whether or not patients undergoing drug therapies should discontinue
      treatment after sustaining a non-vertebral fracture. This study has tested the
      effect of novel active vitamin D3 analog, 1alpha,25-dihydroxy-2beta(3
      hydroxypropoxy)vitamin D3 (ED-71), on the fracture healing comparing with a
      powerful anti-resorptive agent, alendronate, using a rat femoral fracture model.
      MATERIALS AND METHODS: Female SD rats (n=201) allocated into 6 groups were
      treated with MCT-vehicle and ED-71 at 0.025 and 0.05 microg/kg/day (EDL and EDH
      groups), and with saline-vehicle and alendronate at 5 and 10 microg/kg/day (ALL
      and ALH groups). After 4 weeks of pretreatment, osteotomy of the femur was
      performed. Treatment was continued until sacrifice at 6 and 16 weeks post
      fracture. Fracture callus was evaluated by soft X-ray radiography, pQCT,
      biomechanical testing and histomorphometry. RESULTS: At 16 weeks post-fracture,
      new cortical shell appeared in 100% of Control (MCT and saline-vehicle), EDL and
      EHL, and in 67% and 56% of ALL and ALH, respectively. ED-71 treatment showed
      insignificantly large callus area only at 6 weeks, while alendronate treatment
      induced bigger callus at both 6 and 16 weeks post-fracture. The lamellar/callus
      area was decreased only at 6 weeks by ED-71 treatment, but both at 6 and 16 weeks
      by alendronate treatment. Osteoclast number in callus surface was decreased in
      both ED-71 and alendronate treatment groups at 6 weeks and in EDH, ALL and ALH at
      16 weeks, indicating that ED-71 inhibits osteoclastic bone resorption, but its
      effect is less prominent than alendronate. Almost complete callus remodeling was
      observed in ED-71-treated groups at 16 weeks without any significant change in
      structural and material properties of fractured bone. CONCLUSIONS: ED-71
      suppression of callus remodeling by inhibiting osteoclastic bone resorption was
      mild and dose-dependent and did not interfere with natural fracture healing
      process at 16 weeks post-fracture.

PMID- 16962401
TI  - A highly potent inhibitor of cathepsin K (relacatib) reduces biomarkers of bone
      resorption both in vitro and in an acute model of elevated bone turnover in vivo
      in monkeys.
AB  - Cathepsin K is an osteoclast-derived cysteine protease that has been implicated
      as playing a major role in bone resorption. A substantial body of evidence
      indicates that cathepsin K is critical in osteoclast-mediated bone resorption and
      suggests that its pharmacological inhibition should result in inhibition of bone
      resorption in vivo. Here we report the pharmacological characterization of SB
      462795 (relacatib) as a potent and orally bioavailable small molecule inhibitor
      of cathepsin K that inhibits bone resorption both in vitro in human tissue and in
      vivo in cynomolgus monkeys. SB-462795 is a potent inhibitor of human cathepsins
      K, L, and V (K(i, app)=41, 68, and 53 pM, respectively) that exhibits 39-300-fold
      selectivity over other cathepsins. SB-462795 inhibited endogenous cathepsin K in
      situ in human osteoclasts and human osteoclast-mediated bone resorption with IC50
      values of approximately 45 nM and approximately 70 nM, respectively. The anti
      resorptive potential of SB-462795 was evaluated in normal as well as medically
      ovariectomized (Ovx) female cynomolgus monkeys. Serum levels of the C- and N
      terminal telopeptides of Type I collagen (CTx and NTx, respectively) and urinary
      levels of NTx were monitored as biomarkers of bone resorption. Administration of
      SB-462795 to medically ovariectomized or normal monkeys resulted in an acute
      reduction in both serum and urinary markers of bone resorption within 1.5 h after
      dosing, and this effect lasted up to 48 h depending on the dose administered. Our
      data indicate that SB-462795 potently inhibits human cathepsin K in osteoclasts,
      resulting in a rapid inhibition of bone resorption both in vitro and in vivo in
      the monkey. These studies also demonstrate the therapeutic potential of relacatib
      in the treatment of postmenopausal osteoporosis and serves to model the planned
      clinical trials in human subjects.

PMID- 16962404
TI  - Basic transplantation immunology.
AB  - Humans are protected from a daily onslaught of pathogenic organisms by an immune
      system that provides multiple layers of protection. Until solid organ
      transplantation became technically feasible in the early twentieth century, this
      constant state of surveillance for foreign cells that are associated with the
      immune response mostly was viewed as advantageous. Unfortunately for patients who
      have end-stage failure of heart, lungs, kidney, liver, and pancreas, the immune
      system is incapable of distinguishing between the presence of beneficial foreign
      tissue and harmful foreign pathogens; it mounts an effective attack against both.
      Improving our understanding of the factors that initiate and perpetuate the
      alloimmune response will result in the development of more refined and better
      tolerated immunosuppressive strategies.

PMID- 16962405
TI  - Infections complicating solid organ transplantation.
AB  - The requirements for immune suppression after solid organ transplantation
      increases the risk of infection with a myriad of organisms. There are many unique
      and evolving aspects of infection after solid organ transplantation. Advances in
      immunosuppressive therapy and improved protocols for infection prophylaxis have
      resulted in changes in the timing and clinical presentation of opportunistic
      infections. Vigilance in the diagnostic evaluation of suspected infection in the
      solid organ transplant recipient is essential. This article reviews the basic
      evaluation and treatment options for many of the infectious conditions peculiar
      to the immunosuppressed patient.

PMID- 16962406
TI  - The preoperative evaluation of the transplanted patient for nontransplant
      surgery.
AB  - With the improved success of solid-organ transplantation, there has been an
      increased willingness to transplant individuals previously felt to be unsuitable
      for such procedures. Factors such as age and various medical comorbidities are no
      longer considered contraindications to transplantation, and hence, an increasing
      number of recipients may require medical care not specifically related to the
      transplant. After transplantation, many of these patients may require elective or
      emergent surgery, making it important for all surgeons to be familiar with the
      factors that may influence surgical outcomes in this population, asa well asa
      factors that affect postoperative care. Most transplant centres use a team
      approach to manage these complex patients, relying on medical professionals
      experienced in their care and management. Close interaction with the transplant
      team is likely the single most important step in preparing the transplanted
      patient for surgery and managing their postoperative care.

PMID- 16962407
TI  - Perioperative management of immunosuppression.
AB  - Current immunosuppressive regimens typically consist of two phases: induction
      phase (medications given at the time of the initial transplant) and maintenance
      therapy. Induction medications are given to decrease the occurrence of early
      acute rejection, avoid or minimise corticosteroids, and potentially induce long
      term favourable immunoregulatory effects. As tolerance remains an elusive goal,
      life-long maintenance immunosuppression is required after all solid-organ
      transplantations. The various agents used in these two phases of
      immunosuppression are reviewed in this article. The similarities and differences
      between the agents within each class, with respect to efficacy and tolerability,
      are discussed.

PMID- 16962408
TI  - Perioperative concerns for transplant recipients undergoing nontransplant
      surgery.
AB  - At some time in a general surgeon's career it is likely that they will be asked
      to care for a surgical problem in a transplant recipient. In many instances, the
      treating surgeon may opt for transferring the patient to a transplant center more
      familiar with organ transplant recipients, but at other times transfer may not be
      the optimal option for the patient. This article is intended to touch on some of
      the more common situations that a general surgeon in community practice might
      encounter in dealing with organ transplant recipients, and highlight
      perioperative and in a few cases, intraoperative, concerns.

PMID- 16962409
TI  - Gastrointestinal complications following transplantation.
AB  - Gastrointestinal complications are common after kidney, liver, pancreas, heart,
      and lung transplantation. Complications can include gastrointestinal conditions
      preceding the transplantation, viral, fungal, and bacterial gastrointestinal
      infections, and gastrointestinal side effects of medications including
      immunosuppressive agents. Establishing the etiology of gastrointestinal
      complaints is often difficult because any one or a combination of these factors
      might be contributory in the same patient.

PMID- 16962411
TI  - Living kidney donation: evolution and technical aspects of donor nephrectomy.
AB  - For more than 40 years, living donor nephrectomy was performed through a flank
      incision drawn on the urologic experience with nephrectomy for cancer. Since its
      introduction one decade ago, laparoscopic donor nephrectomy has gained widespread
      acceptance and popularity; currently over one-half of donor nephrectomies in the
      United States are performed with this technique. The changing practice of donor
      nephrectomy resembles in many ways the evolution of minimally invasive in other
      subspecialties. The lessons learned from these technical developments are
      valuable and can be adapted by general surgeons and urologists when called upon
      to perform nephrectomy for organ donation or kidney disease.

PMID- 16962410
TI  - Hepatobiliary surgery: lessons learned from live donor hepatectomy.
AB  - The liver is unique in the rapid tissue regeneration occurs after resection or
      injury, and affords the surgeon the opportunity to safely remove up to 60% to 70%
      of the liver volume for treatment of cancer or for use as a live donor graft for
      transplantation. The complex development of the liver and biliary system in utero
      results in multiple and complicated anatomic variations. The hepatobiliary
      surgeon of today must be able to integrate a broadening array of radiologic and
      liver resection techniques that may improve patient safety and surgical outcome.
      Equally important is the ability to quickly recognize postoperative complications
      so that prompt intervention can be instituted. Successful outcome requires a
      balance between sound judgement, technical acumen, and attention to detail.
      Herein, we provide lessons learned from live donor liver transplantation that are
      directly applicable to any patient undergoing major hepatic resection.

PMID- 16962412
TI  - Orthopedic complications of solid-organ transplantation.
AB  - Organ transplantation has undeniably increased the longevity and quality of life
      of patients with end-stage organ failure. Its has, however, introduced the
      skeletal complications of (1) fragility fractures and decreased bone density due
      to pretransplant bone loss and immunosuppressive therapy, and (2) avascular
      necrosis leading to subchondral fracture and secondary osteoarthritis. This
      article reviews these two skeletal complications of solid-organ transplantation
      that lead to structural failure of bone and result in significant morbidity and
      reduced quality of life.

PMID- 16962413
TI  - Skin cancer after transplantation: a guide for the general surgeon.
AB  - The success of organ transplantation has been accompanied by serious concerns
      regarding the incidence and management of potentially catastrophic cutaneous
      carcinogenesis in transplant recipients. Delivery of the highest quality of care
      requires a concerted effort toward collaboration between multiple surgical and
      medical specialties. The purpose of this review is to provide the general surgeon
      with a practical, user-friendly guide to the important components of
      comprehensive dermatologic care for organ transplant recipients (OTRs) with
      references to more detailed sources of information.

PMID- 16962414
TI  - Tolerance, xenotransplantation: future therapies.
AB  - Solid organ transplantation is limited by an insufficient number of organs to
      meet the needs of a growing population of patients with end-organ failure. A
      second problem is that, after successful transplantation, many organs fail owing
      in large part to chronic immunologic injury or so called "chronic rejection". In
      other circumstances, the organ "outlives" the recipient, often because the
      recipient succumbs to medical conditions related to chronic immunosuppression.
      This review focuses on two future therapies that could solve these problems,
      specifically, tolerance induction to permit long-term patient and graft survival
      and xenotransplantation to provide an unlimited supply of donor organs. The
      primary focuses are the most promising ongoing transplantation research that
      could be encountered by clinical surgeons in the near future.

PMID- 16962416
TI  - Molecular cardiology and genetics in the 21st century--a primer.
AB  - The terminology and technology of molecular genetics and recombinant DNA have
      become an essential part of academic cardiology and will soon be applied at the
      bedside. The treatise includes a brief summary of the essentials of the DNA
      molecule, the more common techniques, and their application to genetics and
      molecular cardiology. It is written to be understood by physicians, scientists,
      and paramedical personnel who would not necessarily have a background in
      molecular biology. Inherent in the DNA molecule are three properties fundamental
      to all of the diagnostic and therapeutic applications, namely, the ability of DNA
      to separate into single strands, recombine (annealment or hybridization), and the
      presence of the negative charge enables DNA fragments to be separated easily by
      electrophoresis. Genetic linkage analysis of a family with an inherited disease
      enables one to identify the gene without knowing its protein product. Over 50
      diseases in cardiology due to single-gene disorders have been identified and
      multiple mutations have been detected. The new therapeutic frontier will be stem
      cells and nuclear transfer. Identification of genes responsible for coronary
      artery disease made possible by genome-wide single nucleotide polymorphism (SNP)
      mapping techniques paves the way for personalized medicine.

PMID- 16962419
TI  - MRI of the painful hip in athletes.

PMID- 16962420
TI  - Imaging of femoral acetabular impingement syndrome.

PMID- 16962421
TI  - Sports-related injuries of the knee: an approach to MRI interpretation.

PMID- 16962422
TI  - Imaging of anterior knee pain.

PMID- 16962423
TI  - MRI evaluation of the postoperative knee: special considerations and pitfalls.

PMID- 16962424
TI  - MRI of sports injuries of the ankle.

PMID- 16962425
TI  - Imaging sports medicine injuries of the foot and toes.

PMID- 16962426
TI  - Imaging of stress fractures in runners.

PMID- 16962427
TI  - Sports-related muscle injury in the lower extremity.

PMID- 16962428
TI  - MRI of osteochondral injuries of the knee and ankle in the athlete.

PMID- 16962429
TI  - The role of ultrasound in the evaluation of sports injuries of the lower
      extremities.

PMID- 16962430
TI  - CT Arthrography.

PMID- 16962432
TI  - Sharing the lessons from the past.

PMID- 16962433
TI  - Primary care issues for the healthy premature infant.
AB  - Premature infants born between 32 to 35 weeks' gestation have a 98% survival rate
      and comprise 84% of all preterm infants in the United States. These infants may
      have a relatively benign hospital course and may be considered by some to be a
      "healthy premature infant." At the time of discharge from the neonatal intensive
      care unit, infants will be gaining weight, feeding by mouth, and maintaining
      temperature homeostasis. Support of growth, feeding choices, management of
      gastroesophageal reflux, developmental issues, monitoring at home, and
      recommended special vaccinations are issues that primary care nurse practitioners
      will face in caring for preterm infants. This article is Part II of a three-part
      series focusing on the care of preterm infants after discharge from the neonatal
      intensive care unit. This installment will look specifically at preterm infants
      who are considered to be healthy preterm infants. Part I addressed issues related
      to all premature infants. Part III will focus on the primary care issues in
      medically complex premature infants.

PMID- 16962434
TI  - Herpes zoster in childhood.
AB  - Herpes zoster is caused by reactivation of latent varicella-zoster virus that
      resides in a dorsal root ganglion. Herpes zoster can develop any time after a
      primary infection. Because varicella vaccine is a live attenuated virus, herpes
      zoster can develop in a vaccine recipient. The incidence of herpes zoster among
      vaccine recipients is about 14 cases per 100,000 person-years. In young children,
      herpes zoster has a predilection for areas supplied by the cervical and sacral
      dermatomes. The most common complications are secondary bacterial infection,
      depigmentation, and scarring. Although the diagnosis of herpes zoster is based on
      a distinct clinical appearance, viral DNA analysis of the lesion by polymerase
      chain reaction or restriction fragment length polymorphism is necessary to
      differentiate wild from vaccine-type viruses. Acyclovir is the treatment of
      choice for herpes zoster.

PMID- 16962435
TI  - Shaken baby syndrome education: a role for nurse practitioners working with
      families of small children.
AB  - Nurse practitioners providing primary care to infants and children are in the
      optimal position to address the risk factors and long-term consequences of shaken
      baby syndrome (SBS), a severe form of child abuse, with parents before the child
      is discharged from the nursery or when they come for well-child visits. The
      purpose of this article is to provide a summary of research to date on SBS, state
      and federal efforts aimed at educating citizens about SBS, and the role of nurse
      practitioners in educating the persons who are caring for these vulnerable
      individuals regarding the prevention of SBS.

PMID- 16962436
TI  - Atopic dermatitis in Italian children: evaluation of its economic impact.
AB  - INTRODUCTION: The aim of our study was to evaluate the economic impact of atopic
      dermatitis (AD) on the family of young children affected by the disease in Italy.
      METHODS: Thirty-three families of young children affected by AD were asked to
      fill in a questionnaire about financial costs associated with providing health
      care during the past year for their child affected by AD. For each child AD
      severity was evaluated by using the SCORAD index. RESULTS: By analyzing the
      questionnaire, an annual average cost of 1254euro (about U.S. $1540) for each
      family was determined. Main expenses concern the use of moisturizing therapies,
      particular detergent, and private specialist consultations. Annual family average
      cost was lower for children with mild AD compared with those with moderate to
      severe AD. DISCUSSION: AD has a deep impact on the family budget, with an
      increasing cost in proportion to the increasing severity of the disease. These
      data support previous reports suggesting that the management of AD in children is
      complex and costly, altering the quality of life of children and their families.

PMID- 16962439
TI  - When do pediatric patients graduate?

PMID- 16962437
TI  - Appropriate use of nonprescription analgesics in pediatric patients.

PMID- 16962438
TI  - Premenstrual syndrome and premenstrual dysphoric disorder in adolescence.

PMID- 16962440
TI  - Is it just a seizure?

PMID- 16962441
TI  - Evidence-based practice: what is the evidence for medication adherence in
      children?

PMID- 16962442
TI  - Educating teens about vaccines.

PMID- 16962443
TI  - Environmental toxins.

PMID- 16962444
TI  - The elusive stomach ache.

PMID- 16962446
TI  - The development of Type 2 diabetes in youth.

PMID- 16962448
TI  - Trauma and the obstetric patient: collaboration in care.
AB  - Management of the obstetric patient who suffers a traumatic injury is critically
      dependent o well-coordinated, integrated care. The injured pregnant woman's first
      presentation usually is to the emergency room. Although the first priority is the
      stabilization of pregnancy and active involvement of the obstetric team within
      the trauma and critical care settings enhances patient care and potentiates
      optimal outcome for the mother and fetus.

PMID- 16962449
TI  - Shaken baby syndrome.
AB  - Unfortunately, head trauma caused by shaken baby syndrome is a common occurrence
      in infants and young children. The proper treatment and safety of these children
      can be enhanced by the nurse's ability to recognize features characteristic of
      this syndrome. If abuse is suspected, appropriate physicians, child-protective,
      and law-enforcement agencies should be notified immediately. Further research
      must be done to improve the understanding of the mechanisms associated with this
      disorder in the ultimate hope of improving the lives and outcome of infants and
      children.

PMID- 16962450
TI  - Intimate partner violence: implications for critical care nursing.
AB  - IPV presents a serious health risk to many women. Emergency and critical care
      nurses are in a prime position for identification of and intervention with these
      women. Careful assessment and recognition of symptoms and conditions associated
      with IPV helps nurses to identify victims and potential victims. Building a
      trusting and supportive environment, where women feel comfortable disclosing
      abuse, precedes effective intervention. Nursing practice can incorporate the
      myriad resources and successful programs to provide victims with quality care.
      Before discharge from the critical care unit or ED, nurses can help women to
      identify their risk and plan for safety. Effective nursing care in IPV combines
      the traditional critical care nursing skills synergistically with provision for
      the biopsychosocial needs of patients.

PMID- 16962451
TI  - Firearm violence in america: a growing health problem.
AB  - Firearm injury is a disease that afflicts many individuals in the United States,
      either directly or indirectly. Trauma and critical care nurses have direct
      experience with this life-threatening disease and recognize the high lethality.
      The magnitude of this health problem requires a focus on primary prevention. We
      recognize that any focus on firearm injury is often contentious and political;
      however, nurses bring a ready-made credibility and focus on evidence-based
      practice to the prevention of this disease.

PMID- 16962452
TI  - Workplace violence: a primer for critical care nurses.
AB  - This review illustrates the various types of workplace violence nurses can
      encounter in critical care settings. Lack of a clear definition of workplace
      violence impedes research on the topic; however, the typology offered by the
      UIIPRC provides a framework to guide further studies of physical and nonphysical
      workplace violence. Further investigation of individual and organizational
      factors will assist nurses and agencies in identifying effective methods to
      manage, prevent, educate, and respond to each type of workplace violence. Fear,
      burnout, anxiety, depression, and acute and posttraumatic stress disorders are
      some of the sequelae that can occur after an incident of workplace violence.
      Debriefing strategies should be a fundamental component of workplace violence
      policies to prevent the development of longterm consequences. Additional research
      is needed on all types of workplace violence, as well as research addressing the
      needs of specialized setting, such as critical care unit. Critical care nurses
      have valuable insights regarding the risks they face on their units and should be
      part of a multidisciplinary team developing policies and workplace violence
      prevention and education programs.

PMID- 16962453
TI  - Management of elder sexual abuse cases in critical care settings.
AB  - Elder sexual abuse remains a silent and often invisible crime in persons who have
      limited cognitive abilities. On occasion, physical injury to elders is serious
      enough to require hospitalization and at that point, critical care nurses swing
      into action. In addition to providing acute care interventions, nurses can
      collect important forensic evidence through documenting and photographing
      injuries and reporting suspected cases to proper authorities.

PMID- 16962454
TI  - Care of the critically ill patient with penetrating head injury.
AB  - Patients who have penetrating head injury all too often present with some of the
      most devastating and challenging intracranial injuries. The mechanisms of injury
      and associated neuropathology affect every body system and require a
      multidisciplinary approach. Evidence-based guidelines have been developed to
      offer some direction to clinicians involved in their care. Much remains
      scientifically unsubstantiated, however. Optimal management of critically ill
      patients who have penetrating head injury requires clinical expertise and care of
      the highest quality.

PMID- 16962455
TI  - Blast injuries: from triage to critical care.
AB  - Injuries from explosions are multilayered. Although blast injuries are thought of
      most often in a military context, all nurses need to be prepared to care for
      these casualties. Awareness of the multiple levels of injuries and the need to
      modify care based on the underlying pathology have reduced morbidity and
      mortality in patients who have complex and very critical injuries.

PMID- 16962456
TI  - The psychosocial effects of combat: the frequently unseen injury.
AB  - The psychosocial issues related to deployment and combat duty are complex.
      Deployment may result in psychiatric casualties that are either the result of
      inadequate coping with the stressors of deployment or acute stress reactions
      caused by the trauma of battle, that is, combat stress reactions. Combat duty is
      associated with traumatic events, deprivation, and exposure to war atrocities
      that may result in acute, delayed or chronic psychosocial issues during and afer
      returning from deployment. Although protective and mediating factors ar in place,
      11% to 17% of combat veterans are at risk for mental disorders in 3 to 4 months
      after return from combat duty. Combat veterans include service members directly
      involved in combat as well as those providing support to combatants, that is,
      nurses. All combat veterans are at risk for experiencing the negative effects of
      deployment. Frequent deployments of active duty, reserve, and National Guard
      members have become commonplace. This translates into a disruption of live for
      anyone associated with the military, as well as an increased focus on the
      psychosocial impact of combat across the nation. Modern warfare has resulted in
      multiple changes in policy that govern military operations. Initiatives that
      focus on the stabilization of service members and their families may impact
      mental health outcomes of service members returning from combat duty. An
      initiative toward decreasing the stigma of receiving mental health care is
      warranted. Mental health issues must be addressed before and during deployment to
      ensure optimum individual and unit functioning. Early identification and
      treatment of mental health problems may decrease the psychosocial impact of
      combat and thus prevent progression to more chronic and severe psychopathology
      such as depression and PTSD.

PMID- 16962457
TI  - Survivors' guilt following sudden traumatic loss: promoting early intervention in
      the critical care setting.
AB  - Survivors' guilt is a pervasive mental health issue that is often initially
      manifested by family members in the critical care unit. With increased awareness
      and enhanced targeted assessment, critical care nurses are in a unique position
      to begin the initial processes of adaptive coping and functional grief and
      bereavement in surviving family members. Because the trajectory of grief and
      bereavement are often complex and long term, the additional complication of
      survivors' guilt can lead to many psychosocial and physical manifestations and
      sequelae. However, with early identification and intervention relative to the
      underlying factors of survivors' guilt, including appropriate referral and
      psychoeducational intervention and resources, critical care nurses can enhance
      and extend their care to families in the throes of significant and sudden loss
      and intrapsychic trauma.

PMID- 16962458
TI  - Substance use and abuse in trauma: implications for care.
AB  - Trauma long has been associated with substance use and abuse. Caring for trauma
      patients who are intoxicated, withdrawing, or otherwise experiencing the negative
      outcomes of their substance use is difficult under the best of circumstances. The
      burden of this association can be described in many terms, from economic
      consequences, to health outcomes, to personal problems. Evidence indicates that
      untreated substance-associated trauma carries with it extended hospital stays,
      diminished quality of life, repeat emergency department use, and significant
      mortality and morbidity. No matter how one examines the burden of the association
      between substance use and trauma, one is left with the awareness that nurses can
      improve patient care through better screening, assessment, intervention, an
      evaluation. Because of the complex nature of the association between substance
      use and trauma, nursing care for these patients is difficult. Fig. 1 provides an
      overview of the factors to consider when planning care for these patients. Nurses
      need to focus on issues of temporality, directionality, and correlates of care as
      they plan for the needs of their patients. Only with careful considerations of
      these factors can the nurse clarify the confounding clinical presentation of the
      trauma overlaid on substance use. Evidence supports the need for all trauma
      patients to be screened for substance use and for those who have positive screens
      to receive early intervention. Although there is almost universal awarenes of the
      of the association between substance use and trauma and of the value of
      screening, screening rates for trauma patients are surprisingly low. Screening
      for substance use followed by BMI intervention is cost effective and should be
      implemented routinely. The high prevalence of substance-associated trauma,
      coupled with the heterogeneous nature of that association, warrants more study,
      particularly nursing research, to determine best-care practices. More research is
      needed to increase the understanding of patterns of use, etiologic models, and
      effective clinical care strategies. The need for this research is heightened by
      the awareness that substance-associated trauma is preventable, and the risk is
      modifiable. Nurses, everyday, are faced with the daunting challenge of meeting
      the health needs of trauma patients who have associated substance use. More
      research is needed to help nurses separate out the confounding health needs of
      these complex patients. That work has begun, and it assuredly will continue to
      support the need for high-quality nursing interventions to improve the health of
      trauma patients.

PMID- 16962459
TI  - A historical review of penetrating abdominal trauma.
AB  - The course of history changed because of the deaths of these two men. Although
      the world doesn't remember Chester Allan Arthur (JAG's Vice President), Theodore
      Roosevelt became one of our most popular presidents. Neither president's injuries
      were life-threatening, but they died of postoperative complications. The
      technology and treatment used for penetrating abdominal trauma have changed
      tremendously over the past 100 years. Both presidents would survive if they
      sustained their injuries today.

PMID- 16962460
TI  - Fire and smoke injuries.
AB  - The successful management of burns and related injuries requires a comprehensive
      team approach at a designated burn center. This team should consist of burn
      surgeons, burn nurses, respiratory therapists, physical therapists, occupational
      therapists, clinical nutritionists, social workers, chaplains, and other clinical
      consultants. This article focuses specifically on the management of thermal burns
      and inhalational injuries, with an emphasis on assessment, resuscitation, and
      critical care management. It also discusses special considerations related to
      burned trauma patients.

PMID- 16962461
TI  - Traumatic injury in the older adult from head to toe.
AB  - This review demonstrates essential issues to consider when caring for older
      trauma patients, including baseline physical status, mental health,
      comorbidities, and risk factors for sequelae and future injuries. The impact of a
      traumatic injury on older adults is complex. Issues of normal aging, functional
      status, chronic health conditions, and response to treatment affect health care
      and related decisions. Studies that have examined outcomes for older trauma
      patients to date have been mainly descriptive or confined to a single
      institution, limiting our ability to generalize. Other studies, using large data
      sets, have provided some information regarding possible primary prevention
      strategies, yet have limitations in the individual level detail collected.
      Nevertheless, this review also demonstrates the dearth of available evidence
      based recommendations that provides support to treatment protocols in this
      complex and diverse patient population. The lack of an evidence base to use in
      the management of older trauma patients demonstrates the critical need for
      research in this rapidly growing population. An example of one such area includes
      the use of pulmonary artery catheters in older trauma patients. Although evidence
      to date suggests that pulmonary artery catheters are of benefit in the management
      of patients with physiologic compromise, it is unclear whether using these
      published cardiac output management recommendations leads to improved outcomes.
      In light of newly published data suggesting equivocal benefit from use of
      pulmonary artery catheters, with increased side effects, this controversy is an
      important area for future research. Critical care nurses, with their emphasis on
      multidisciplinary, holistic practice, can expand their influence as essential
      members of the interdisciplinary team caring for older trauma patients by
      cultivating geriatric specialty knowledge. Older trauma patients would benefit
      greatly from this type of specialty nursing care during all phases of the
      recovery trajectory, particularly in terms of adequate symptom management and
      prevention of sequelae, as well as with timely and appropriate initiation of
      consultative services. Using the intersection of primary and secondary prevention
      as the overall guide for practice, critical care nurses and other health care
      providers who possess an understanding of aging processes and comorbid conditions
      can significantly improve outcomes for older adults with traumatic injuries.

PMID- 16962462
TI  - Rationale and process: International Society for Heart and Lung Transplantation
      guidelines for the care of cardiac transplant candidates--2006.

PMID- 16962463
TI  - Optimal pharmacologic and non-pharmacologic management of cardiac transplant
      candidates: approaches to be considered prior to transplant evaluation:
      International Society for Heart and Lung Transplantation guidelines for the care
      of cardiac transplant candidates--2006.

PMID- 16962464
TI  - Listing criteria for heart transplantation: International Society for Heart and
      Lung Transplantation guidelines for the care of cardiac transplant candidates-
      2006.

PMID- 16962465
TI  - Heart rhythm considerations in heart transplant candidates and considerations for
      ventricular assist devices: International Society for Heart and Lung
      Transplantation guidelines for the care of cardiac transplant candidates--2006.

PMID- 16962466
TI  - HLA-DR matching improves survival after heart transplantation: is it time to
      change allocation policies?
AB  - BACKGROUND: HLA matching has improved outcome in kidney transplantation but is
      not considered in current allocation policies in heart transplantation. The aim
      of this single-center study was to assess the impact of HLA matching on long-
      term outcome after heart transplantation. METHODS: The records of 240 consecutive
      heart transplant recipients (time period 1995 to 2002; mean age 51.8 +/- 11.7
      years; mean follow-up 5.9 +/- 1.8 years) were analyzed retrospectively. According
      to the renal allocation policy, HLA mismatches (MM) on the major antigen loci HLA
      A, HLA-B and HLA-DR were calculated, demonstrating 0 to 6 MM. Patients with
      primary graft failure were excluded from statistical analysis. RESULTS: Survival
      analysis revealed a statistically significant impact of HLA-DR MM on survival.
      Five-year survival was 90% in patients without HLA-DR MM (n = 10), 79% in
      patients with 1 HLA-DR MM (n = 113), and 68.1% in patients with 2 HLA-DR MM (n =
      117) (1 MM vs 2 MM: p < 0.05). Freedom from cardiac allograft vasculopathy after
      5 years was 89% in HLA-DR-identical recipients (n = 10), 61% in patients with 1
      HLA-DR MM (n = 102), 54% in patients with 2 HLA-DR MM (n = 104). Conventional
      matching with 6 mismatches over the three major HLA antigen loci revealed a trend
      toward a higher relative risk for adverse outcome in patients with increased MM.
      CONCLUSIONS: HLA-DR matching had a significant impact on survival after heart
      transplantation (HTx) at our center. In the effort to achieve the best
      comparative use of scarce donor organs the inclusion of HLA-DR matching into
      allocation policies might improve long-term outcome after HTx.

PMID- 16962467
TI  - Multicenter retrospective analysis of cardiovascular risk factors affecting long
      term outcome of de novo cardiac transplant recipients.
AB  - BACKGROUND: Previous risk factor studies in cardiac transplant patients have
      analyzed pre-transplant risk factors as they relate to outcomes. This study is
      the first in-depth multicenter assessment of ongoing post-transplant risk factors
      in heart transplant patients and their impact on 5-year outcomes. METHODS: We
      reviewed 280 heart transplant patients who survived > 1 year for the impact of
      post-transplant risk factors (hyperlipidemia, hypertension, diabetes, body mass
      index [BMI] and renal dysfunction: 8 to 18 possible measurements over 5 years) on
      outcomes, including death, cardiac allograft vasculopathy (CAV) and non-fatal
      major adverse cardiac events (NF-MACE). RESULTS: Upon multivariate Cox regression
      analysis, significant findings were high total-cholesterol for NF-MACE (relative
      risk [RR] = 4.34, confidence interval [CI] 1.35 to 13.98, p = 0.01), presence of
      diabetes for NF-MACE (RR = 3.96, CI 1.24 to 12.65, p = 0.02) and high serum
      creatinine for graft death (RR = 1.59, CI 1.35 to 1.87, p < 0.001). No covariates
      were found to be significant for CAV. Other significant risk factors by
      univariate Cox regression models with time-dependent covariates included BMI > or
      = 33 for graft death. CONCLUSIONS: Post-transplant risk factors of
      hypercholesterolemia and diabetes are associated with NF-MACE, whereas high serum
      creatinine and BMI > or = 33 are associated with graft death. Risk factor
      modification, including direct therapy to minimize risk factors, should be
      considered.

PMID- 16962468
TI  - Prostaglandin E1 testing in heart failure-associated pulmonary hypertension
      enables transplantation: the PROPHET study.
AB  - BACKGROUND: Elevated pulmonary vascular resistance (PVR) is relevant to prognosis
      of congestive heart failure and heart transplantation. Proof of reversibility by
      pharmacologic testing in potential transplantation candidates is important
      because it indicates a reduced probability of right ventricular failure or death
      in the early post-transplant period. This study aimed to clarify the possible
      extent of acute reversibility of elevated PVR in a large, consecutive cohort of
      heart transplant candidates. METHODS: This study included 208 consecutive
      patients (age 52 +/- 10 years, 89% men and 11% women, ejection fraction 21 +/-
      9%, Vo2max 12.6 +/- 4.2 ml/kg/min) being evaluated for heart transplantation in 7
      transplant centers in Germany and Switzerland. Testing was performed with
      increasing intravenous doses of prostaglandin E1 (PGE1; average maximum dose 173
      +/- 115 ng/kg/min for at least 10 minutes) in 92 patients exhibiting a baseline
      PVR of > 2.5 Wood units (WU) and/or a transpulmonary gradient (TPG) of > 12 mm
      Hg. RESULTS: PGE1 testing lowered PVR from 4.1 +/- 2.0 to 2.1 +/- 1.1 WU (p <
      0.01), increased cardiac output from 3.8 +/- 1.0 to 5.0 +/- 1.5 liters/min (p <
      0.01), and decreased TPG from 14 +/- 4 to 10 +/- 3 mm Hg (p < 0.01), mean
      pulmonary artery pressure (PAM) from 39 +/- 9 to 29 +/- 9 mm Hg (p < 0.01) and
      mean pulmonary capillary wedge pressure (PCWP) from 24 +/- 7 to 19 +/- 9 mm Hg (p
      < 0.01). Mean aortic pressure (MAP) decreased to 85% and systemic vascular
      resistance (SVR) to 65% of baseline values (p < 0.01). Symptomatic systemic
      hypotension was not observed. For the whole population the percentage of patients
      with PVR > 2.5 WU was reduced from 44.2% to 10.5% with PGE1. PVR decreased in
      each patient; only 2 patients (1%) remained ineligible for listing because of a
      final PVR of > 4.0 WU. TPG, ejection fraction and male gender were independent
      predictors of reversibility of PVR. CONCLUSIONS: Elevated PVR in heart transplant
      candidates is highly reversible and can be normalized during acute pharmacologic
      testing with PGE1.

PMID- 16962469
TI  - Delayed gastric emptying scintigraphy in cystic fibrosis patients before and
      after lung transplantation.
AB  - BACKGROUND: The purpose of this study was to assess the rate of gastric emptying
      (GE) in cystic fibrosis patients scheduled for lung transplantation. METHODS:
      Thirty patients (20 males, 10 females, 22.6 +/- 6.4 years) were evaluated by GE
      scintigraphy before (1.58 +/- 1.11 years) and early after (5.8 +/- 2.6 weeks)
      heart-lung transplantation (n = 13) or lung transplantation (n = 17). Solid
      retention rates at 2 hours (RR2) and 3 hours (RR3) and half-emptying times (T50)
      of solids and liquids obtained before transplantation were compared with those
      after transplantation. Data were also compared with those obtained from a control
      group of 53 healthy volunteers. RESULTS: Before surgery, 20 patients (67%) showed
      a delayed GE (T50 of solids: patients 160.86 +/- 59.21 minutes vs controls 75.43
      +/- 15.13 minutes, p < 0.0001), and 4 of them also had a delayed T50 of liquids.
      After surgery, the T50 of solids was considered unreliable (too much stasis) in
      24 patients. Thus, analyses were done on the basis of solid retention rates.
      Twenty-nine patients (97%) showed very delayed GE compared with controls (p <
      0.0001), 20 of whom also had a delayed T50 of liquids. RR2 and RR3 were
      significantly higher after surgery than before (RR2 = 86 +/- 17% and RR3 = 77 +/-
      22% vs 50 +/- 24% and 27 +/- 24% after and before surgery, respectively, p <
      0.0001). However, there was no correlation between pre- and post-transplantation
      scintigraphy results. CONCLUSIONS: Delayed GE of solids was a frequent
      abnormality in patients with end-stage cystic fibrosis, with a dramatic delay
      after surgery in almost all patients. These results emphasize the need for early
      management of such patients by dietary manipulation or prokinetic medications.

PMID- 16962470
TI  - Effect of clenbuterol on cardiac and skeletal muscle function during left
      ventricular assist device support.
AB  - BACKGROUND: High-dose clenbuterol (a selective beta2-adrenergic agonist) has been
      proposed to promote myocardial recovery during left ventricular assist device
      (LVAD) support, but its effects on cardiac and skeletal muscle are largely
      unknown. METHODS: Seven subjects with heart failure (5 ischemic, 2 non-ischemic)
      were started on oral clenbuterol 5 to 46 weeks post-LVAD implantation and up
      titrated to daily doses of 720 microg. The following procedures were performed at
      baseline and after 3 months of therapy: echocardiography at reduced support (4
      liters/min); cardiopulmonary exercise testing; body composition analysis; and
      quadriceps maximal voluntary contraction (MVC). Myocardial histologic analysis
      was measured at device implantation and explantation. RESULTS: There were no
      serious adverse events or arrhythmias. Creatine phosphokinase (CPK) was elevated
      in 4 subjects, with no clinical sequelae. No change in ejection fraction was
      seen. End-diastolic dimension increased significantly (4.73 +/- 0.67 vs 5.24 +/-
      0.66; p < 0.01), despite a trend toward increased LV mass. Body weight and lean
      mass increased significantly (75.5 +/- 17.9 vs 79.2 +/- 25.1 kg, 21.1 +/- 8.9 vs
      23.6 +/- 9.7 kg, respectively; both p < 0.05). Exercise capacity did not change,
      but MVC improved significantly from 37.0 +/- 15.7 to 45.8 +/- 20.6 kg (p < 0.05).
      No significant change in myocyte size or collagen deposition was seen.
      CONCLUSIONS: Cardiac function did not improve in this cohort of LVAD patients
      treated with high-dose clenbuterol. However, clenbuterol therapy increased
      skeletal muscle mass and strength and prevented the expected decrease in myocyte
      size during LVAD support. Further study will clarify its potential for cardiac
      and skeletal muscle recovery.

PMID- 16962471
TI  - Reverse remodeling of the myocardial extracellular matrix after prolonged left
      ventricular assist device support follows a biphasic pattern.
AB  - BACKGROUND: Collagens are important components of the extracellular matrix (ECM).
      Alterations in collagen structure and composition can lead to end-stage heart
      failure. Left ventricular assist devices (LVADs) are frequently used as a bridge
      to heart transplantation (HTx). In this study, we analyzed changes in composition
      of the collagens as well as the synthesis or degradation of these collagens after
      prolonged LVAD support. METHODS: The ECM volume was quantified after Picro-Sirius
      red staining. With immunohistochemistry (IHC), Type I and Type III collagen
      proteins were analyzed and, using quantitative polymerase chain reaction (PCR),
      collagen mRNA expression was analyzed. Collagen synthesis and degradation was
      studied by measuring N-terminal pro-peptide for Type I collagen (PINP), N
      terminal pro-peptide for Type III collagen (PIIINP) and carboxyterminal
      telopeptide for Type I collagen (ICTP) in plasma. Collagen composition was
      measured using the hydroxyproline/Sircol assay. RESULTS: The ECM volume increased
      in the first 200 days after LVAD implantation. At between 200 and 400 days the
      ECM volume decreased, but remained higher than pre-LVAD. After 400 days the ECM
      volume was smaller than the pre-LVAD volume. IHC did not show a significant
      difference pre- and post-LVAD for collagen composition. Collagen mRNA expression
      did not change but an augmented synthesis of collagen during the first month
      after LVAD support was detected upon measurement of plasma PINP and PIIINP
      levels. In addition, the quality of the collagen network improved. CONCLUSIONS:
      Reverse remodeling during LVAD support follows a biphasic pattern. Initially, an
      increase in Type I and Type III collagen turnover occurs, which is paralleled by
      a volume increase of the ECM. Subsequently, this turnover decreases as ECM volume
      decreases, which results in a restoration of the collagen network.

PMID- 16962472
TI  - Age-dependent chronic rejection after experimental heart transplantation.
AB  - BACKGROUND: The progressive decline of allograft function is predominantly a
      consequence of chronic rejection, but the etiology of this process is not fully
      understood. To evaluate the influence of age we performed heart transplantation
      in an experimental model of chronic rejection using inbred rats of different age.
      METHODS: Lewis rats served as donors and F344 rats were used as recipients. Young
      rats were 4 weeks of age, whereas adult rats were 4 months of age. Transplanted
      animals were grouped as follows: Group I, old to old; Group II, old to young;
      Group III, young to old; and Group IV, young to young. Intra-abdominal
      heterotopic heart transplantation was performed. Thereafter, functional
      evaluation was performed by daily palpation and surface electrocardiogram (ECG)
      to calculate the functional heart rejection index (fHRI). One month after
      transplantation the hearts were explanted and examined pathohistologically.
      RESULTS: Functional deterioration was noted in all groups, but all hearts were
      still beating when explanted. Young recipients and young donors showed
      significantly better results. Transplantation of young recipients led to a better
      fHRI (p < 0.001) and to a less critical chronic graft vasculopathy, especially
      when there was a young heart transplanted (p = 0.03). Furthermore, whenever a
      young donor heart was used, there was a better graft performance and less severe
      chronic rejection (p = 0.02). CONCLUSIONS: Experimental cardiac transplantation
      of young hearts leads to a better graft performance as well as to a lower
      incidence of a severe chronic graft disease. Thus, older donor age may adversely
      influence long-term performance of cardiac allografts.

PMID- 16962473
TI  - Assessment of cardiac allograft vasculopathy late after heart transplantation:
      when is coronary angiography necessary?
AB  - BACKGROUND: Cardiac allograft vasculopathy (CAV) represents a major prognostic
      factor in long-term survivors of heart transplantation (HTx). Reliable diagnosis
      of CAV late after HTx is important but remains the domain of invasive techniques
      such as coronary angiography. METHODS: To test alternative approaches, 54
      consecutive HTx recipients (mean time since HTx: 52 months) were studied with
      intravascular ultrasound (IVUS), angiography, dobutamine stress echocardiography
      and immunofluorescence staining against anti-thrombin III (AT-III) in
      endomyocardial biopsies. Univariate and multivariate predictors as well as
      receiver-operating-characteristic (ROC) curves of different sets of predictors
      were calculated. RESULTS: Using IVUS as reference standard, CAV was present in
      80% of subjects. Coronary angiography identified CAV correctly in only 44% of
      cases. If AT-III staining alone was used as a diagnostic criterion, CAV was
      correctly identified in 77% of subjects. In a multivariate analysis, only AT-III,
      donor age and echocardiography at rest emerged as independent predictors of CAV
      (p < 0.05 for all), yielding an excellent discriminative power. CONCLUSIONS: With
      almost equal reliability when compared with IVUS, CAV can be identified using
      information on donor age, wall motion score at rest and AT-III staining late
      after HTx. Coronary angiography may be limited to patients with a high
      probability score and should not be used routinely for surveillance of CAV.

PMID- 16962474
TI  - CD26/dipeptidylpeptidase IV-targeted therapy of acute lung rejection in rats.
AB  - BACKGROUND: CD26 is a T-cell co-stimulator, and interacts with adenosine
      deaminase, human immunodeficiency virus (HIV) Tat-1 protein and extracellular
      matrix. It possesses dipeptidylpeptidase IV (DPP IV) catalytic activity, which is
      linked to its co-stimulatory efficacy. We investigated the effect of specific DPP
      IV systemic activity inhibition on acute pulmonary rejection. METHODS: Rat single
      lung transplantation (Tx) was performed (LBNF1/LEW donor/recipient) in two groups
      (n = 12). Group I (n = 6) received daily treatment with a Pro-Pro
      diphenylphosphonate derivative (AB197), and Group II served as an untreated
      control. At Day 5 post-Tx, ventilatory parameters, cytotoxicity and mixed
      lymphocyte reaction were analyzed and staining for ISHLT rejection grade and
      proliferating cell nuclear antigen (PCNA) was performed. RESULTS: Treatment with
      AB192 abrogated acute rejection and preserved pulmonary function up to Day 5 post
      Tx for PO2 (Group II: 24.9 +/- 6.9 mm Hg; Group I: 149.5 +/- 24.3 mm Hg; p <
      0.001), PCO2 (Group II: 53.3 +/- 13.6 mm Hg; Group I: 39.0 +/- 9.8 mm Hg; p <
      0.05) and peak airway pressure (Group II: 50.7 +/- 17.2 mm Hg; Group I: 20.2 +/-
      10.0 mm Hg; p < 0.01). Controls showed moderate/severe rejection (ISHLT Grade A2
      or 3), grafts from inhibited hosts revealed no/mild rejection (Grade A0 to 2:
      Group II: 2.8 +/- 0.3; Group I: 1.25 +/- 1.0; p < 0.005). Proliferating cell
      nuclear antigen (PCNA) staining of rejection-associated cellular infiltrates
      showed a significant reduction in positivity in perivascular infiltrates (34 +/-
      11.5%; p < 0.05) and bronchial surface epithelium (31.7 +/- 10.6%; p < 0.05) in
      Group I vs Group II (55.9 +/- 8.4% and 57.2 +/- 4.5%). CONCLUSIONS: Irreversible
      enzymatic inhibition of DPP IV has been shown to abrogate acute pulmonary
      rejection, maintain pulmonary function, and preserve histomorphologic
      architecture. These results extend earlier findings and illustrate the role of
      CD26/DPP IV in alloantigen-mediated immune responses.

PMID- 16962475
TI  - Increased expression of the renin-angiotensin system and mast cell density but
      not of angiotensin-converting enzyme II in late stages of human heart failure.
AB  - BACKGROUND: The activation of the renin-angiotensin system (RAS) contributes to
      the progression of left ventricular dysfunction. A novel human homologue of the
      angiotensin-converting enzyme (ACE), named ACE2, has been described but its role
      in human heart failure (HF) has not been elucidated. Besides, there is
      controversy as to whether the major angiotensin II-forming-activity in heart is
      ACE or chymase released from mast cells. Furthermore, long-term blockade of
      nitric oxide (NO) synthesis has been shown to increase ACE activity. To assess
      the locally activated vasoactive mediators that may contribute to the ventricular
      deterioration process, we sought to simultaneously analyze their expression in
      failing hearts. METHODS: We analyzed left ventricular biopsies from 30 patients
      with heart failure undergoing heart transplantation and 12 organ donors. The mRNA
      levels of ACE, ACE2, chymase and endothelial nitric oxide synthase (eNOS), were
      quantified by real-time polymerase chain reaction and mast cell density was
      assessed by immunohistochemistry. The mRNA levels of the atrial natriuretic
      peptide (ANP) and the brain natriuretic peptide (BNP) were also quantified as
      controls. RESULTS: There was higher ACE and chymase mRNA expression and mast cell
      density in failing than in control myocardium and no changes in ACE2 expression
      were detected. eNOS mRNA levels were lower in failing hearts. Both ANP and BNP
      expression were higher in pathological than in control samples. CONCLUSIONS:
      These data document a decompensation of vasoactive systems that may contribute to
      the progressive impairment of the myocardial function in HF. On the other hand,
      ACE2 mRNA expression is not altered in human end-stage HF.

PMID- 16962476
TI  - Cellular mechanisms responsible for the inotropic action of insulin on failing
      human myocardium.
AB  - BACKGROUND: An increase in intracellular calcium transients is responsible for
      the positive inotropic effect of insulin on human myocardium, but the mechanisms
      involved in this increase in [Ca2+]i remain unclear. METHODS: We studied isolated
      trabeculae or cardiomyocytes from end-stage failing hearts of 38 patients
      undergoing heart transplantation. The effect of insulin on isometric twitch force
      (37 degrees C, 0.5 Hz) and L-type Ca2+ current (whole-cell voltage clamp) was
      assessed. RESULTS: Crystalline insulin increased the contractile force in a dose
      dependent manner (0.01 to 10 micromol/liter), with a maximum increase of 45 +/-
      8% (p < 0.05) at 1 micromol/liter. It also increased L-type Ca2+ peak current
      density by 26 +/- 6% (p < 0.05). This insulin-mediated positive inotropic effect
      was unchanged in the presence of propranolol (1 micromol/liter). Positive
      inotropy was partially independent of glucose. L-type Ca2+ channel blockade
      (diltiazem, 5 micromol/liter), and sarcoplasmic reticulum (SR) Ca2+-release
      channel blockade (ryanodine, 0.1 micromol/liter) did not affect the inotropic
      response to insulin. However, blockade of SR Ca2+-ATPase (cyclopiazonic acid, 10
      micromol/liter), inhibition of Na+-H+ exchange (HOE642, 10 micromol/liter), and
      inhibition of Na+-Ca2+ exchange (SEA0400, 1 micromol/liter) partially prevented
      the inotropic response to insulin. CONCLUSIONS: Positive inotropy of insulin was
      not related to catecholamine release and subsequent stimulation of beta
      adrenergic receptor, but it may enhance the activity of SR Ca2+-ATPase and trans
      sarcolemmal Ca2+ entry, mainly via reverse-mode Na+-Ca2+ exchange and insulin
      mediated activation of Na+-H+ exchange. We hypothesize that these changes in
      [Ca2+]i might be secondary to the activation of reverse-mode Na+-Ca2+ exchange,
      presumably via elevated intracellular Na+ concentration.

PMID- 16962477
TI  - N-terminal pro-brain natriuretic peptide, kidney disease and outcome in patients
      with chronic heart failure.
AB  - BACKGROUND: In patients with chronic heart failure (CHF), N-terminal pro-brain
      natriuretic peptide (NT-proBNP) provides relevant prognostic information, but its
      usefulness in the presence of kidney disease has been questioned. METHODS: We
      prospectively enrolled 142 patients with stable CHF and a wide spectrum of renal
      function (estimated glomerular filtration rates [eGFRs] ranging from 17.1 to
      100.3 ml/min/1.73 m2). Chronic kidney disease, defined as eGFR < 60 ml/min/1.73
      m2, was present in 63 patients (44%). NT-proBNP measurements were carried out on
      a bench-top analyzer (Elecsys 2010). Cardiac death or urgent cardiac
      transplantation were considered as a combined study end-point. RESULTS: During a
      follow-up of 383 +/- 237 days, 19 patients underwent a cardiac event (cardiac
      death, n = 17; urgent cardiac transplantation, n = 2). By multivariate Cox
      analysis, including clinical and laboratory variables, NT-proBNP and serum
      hemoglobin were independent prognostic predictors. In patients with NT-proBNP >
      1,129 pg/ml, outcome was significantly worse compared to patients with NT-proBNP
      < 1,129 pg/ml (event-free survival rate 67% vs 94% in those with NT-proBNP <
      1,129 pg/ml, p = 0.001). By linear regression analysis, NT-proBNP levels were
      related to New York Heart Association (NYHA) functional class (R = 0.41, p <
      0.001), and inversely related to eGFR (R = -0.29, p = 0.001) and to left
      ventricular ejection fraction (R = -0.43, p < 0.001). CONCLUSIONS: In CHF
      patients with and without kidney disease, NT-proBNP provides independent
      prognostic information. In such patients, NT-proBNP levels are not only
      reflective of a reduced clearance (i.e., a lower eGFR) but also of the severity
      of the underlying structural heart disease.

PMID- 16962478
TI  - Permanent pacing after cardiac transplantation in the era of extended donors.
AB  - BACKGROUND: Early results with bicaval anastomosis have shown a decreased
      requirement for permanent pacing (PPM) after transplantation (Tx). It is unclear
      whether this remains true in the current era of extended donor criteria. The
      objective of the present study was to characterize the need for post-Tx PPM
      requirements in the current bicaval era and to determine factors associated with
      need for pacing. METHODS: The local cardiac Tx database, hospital records and
      electrophysiology laboratory database were cross-referenced for information on
      patients in the pre-, peri- and post-Tx period. RESULTS: Between 2000 and 2004,
      88 patients received a cardiac Tx using bicaval anastomosis. At post-Tx, 18 of 88
      (20.5%) patients required a PPM. The incidence of single- and dual-chamber PPM
      was 31.3% and 68.7%, respectively. Mean donor age for patients requiring post-Tx
      PPM was 44.7 +/- 15.3 years compared with 35.7 +/- 14.4 years for those with no
      PPM requirement (p = 0.019). For every 5-year increase in donor age the risk for
      post-Tx PPM increased 1.234-fold (95% confidence interval [CI] 1.022 to 1.489, p
      = 0.0289). Recipient age, gender, amiodarone use, year of transplant, surgeon and
      surgical times were not associated with PPM requirements after cardiac Tx.
      CONCLUSIONS: Pacing requirements after heart transplantation, in the era of
      extended donor criteria, exceed the previously published rates of 0% to 5%. The
      advantage of bicaval anastomosis in decreasing pacing needs post-Tx does not
      exist in the era of extended donor criteria, specifically in the older donor age
      group.

PMID- 16962479
TI  - Post-mortem administration of urokinase in canine lung transplantation from non
      heart-beating donors.
AB  - BACKGROUND: We previously reported that post-mortem heparinization by closed
      chest cardiac massage within 30 minutes after cardiac arrest is beneficial in
      lung transplantation (LTx) from non-heart-beating donors (NHBDs) by preventing
      formation of microthrombi. In this study, we evaluated the effects of post-mortem
      administration of urokinase 60 minutes after cardiac arrest. METHODS: Left LTx
      was performed in 12 pairs of mongrel dogs. Donors were sacrificed and left at
      room temperature for 2 hours. In Group 1 (n = 6), heparin sodium (1,000 U/kg) was
      administered intravenously 60 minutes after cardiac arrest, then closed-chest
      cardiac massage was performed for 1 minute to distribute the heparin. In Group 2
      (n = 6), the donors were treated as in Group 1, except, in addition to heparin
      sodium, urokinase (120,000 U) was administered intravenously before and at the
      end of cardiac massage. After 2 hours of cardiac arrest, donor lungs were flushed
      with low-potassium dextran glucose solution. After left LTx, the right pulmonary
      artery was ligated, and recipients were followed up for 3 hours. Uni- and
      multivariate repeat analyses were performed to obtain statistical data. RESULTS:
      Group 2 had significantly better arterial oxygen tension, lower pulmonary
      vascular resistance and lower wet/dry weight ratio of the transplanted lung than
      Group 1. d-dimer level during the warm ischemia was significantly lower in Group
      2 than in Group 1. CONCLUSIONS: Post-mortem administration of urokinase along
      with heparin is beneficial in LTx from NHBDs by fibrinolytic action on already
      formed pulmonary microthrombi in the cadaver donor lungs.

PMID- 16962480
TI  - Ten-year follow-up of a prospective, randomized trial of BT563/bb10 versus anti
      thymocyte globulin as induction therapy after heart transplantation.
AB  - BACKGROUND: Alloantigen-activated T cells express high-affinity interleukin-2
      receptor (IL-2R). Specific blockade of this receptor has been associated with
      lower rejection episodes in clinical transplantation when compared with placebo.
      The first short-term results of the newer IL-2R antagonists are becoming
      available but little is known about the long-term effects of these drugs. The aim
      of the study was to compare the clinical efficacy of the IL-2R antagonist BT563
      with polyclonal rabbit anti-thymocyte globulin (ATG) in heart transplant
      recipients. METHODS: Forty patients undergoing cardiac transplantation were
      randomly assigned to receive either BT563 or rabbit ATG as induction therapy,
      combined with triple immunosuppression thereafter. Ten-year surveillance for
      rejection, infection, allograft vasculopathy and tumorgenicity was performed.
      Allograft rejection and vasculopathy were assessed by endomyocardial biopsy and
      coronary angiography, respectively. Screening for infection included blood, urine
      or tracheobronchial cultures and serology. RESULTS: No difference was detected in
      terms of 10-year survival between the two groups (50% for the IL-2R group and 70%
      for the ATG group, p = 0.16). Actuarial incidence of severe rejection was
      significantly higher in the IL-2R group (55% vs 10% at 10 years post-operatively,
      p = 0.028; 55% vs 5% during the first month post-operatively, p = 0.0005).
      Patients receiving ATG had a higher incidence of viral infection. Freedom from
      allograft vasculopathy was significantly higher in the ATG group (80% vs 60%, p =
      0.031). CONCLUSIONS: BT563/BB10 is less effective than ATG for prevention of both
      acute allograft rejection and allograft vasculopathy after cardiac
      transplantation. Clinically relevant infections or tumorgenicity were not
      increased with the use of ATG.

PMID- 16962481
TI  - Topical anesthesia with EMLA reduces pain during endomyocardial biopsy: a
      randomized trial.
AB  - Cardiac transplant recipients often anticipate and suffer varying degrees of
      discomfort during surveillance endomyocardial biopsy (EMBx). We performed a
      randomized, blinded, placebo-controlled trial to determine whether topical
      anesthetic was associated with reduced pain and to identify factors associated
      with increased pain perception during EMBx. In 225 EMBxs, use of the eutectic
      mixture of lidocaine and prilocaine (EMLA) decreased pain score (-7.3 compared
      with placebo; p = 0.04); the other significant predictors of increased pain
      scores were time to achieve access (+2.3 per minute; p = 0.001) and female gender
      (+12.7 compared with males; p = 0.003). Topical anesthetic cream is associated
      with decreased pain during EMBx, even after adjusting for other predictors of
      pain, including female gender and longer time to achieve access. A better
      understanding of the factors affecting pain during EMBx could improve the comfort
      level of this procedure.

PMID- 16962482
TI  - Effects of lung allocation score on waiting list rankings and transplant
      procedures.
AB  - The effect of the new lung allocation score on ranking of patients on the waiting
      list and the number of transplants performed is not known. We assessed this
      effect on our lung transplant program and conducted a simulation of lung
      transplants for the first few months of the new system, using the old waiting
      lists. Patients with idiopathic pulmonary fibrosis had improved rankings and
      patients with emphysema had worse rankings, but the number of transplants for
      each disease category did not change significantly compared with the simulated
      transplants.

PMID- 16962483
TI  - Sirolimus-associated interstitial pneumonitis in 3 heart transplant recipients.
AB  - Sirolimus-induced interstitial pneumonitis (SIP) has been reported mainly in
      renal transplant recipients. However, it has recently been reported with
      increasing frequency in heart transplantation (HT) patients switched from
      calcineurin inhibitors (CNIs) to sirolimus. We reviewed the medical records of 30
      patients who were treated with sirolimus. Twenty-seven patients were switched
      from a CNI, 2 patients were initially treated with sirolimus and in 1 patient
      sirolimus was used to treat a persistent cellular acute rejection. Three patients
      developed SIP. Symptoms included dry cough, shortness of breath and hypoxemia.
      High-resolution computed tomography (HRCT) scans showed patchy pulmonary
      consolidation in a peribronchial distribution or diffuse interstitial pulmonary
      infiltrates. Before onset of SIP, 2 patients had previous heart failure.
      Sirolimus discontinuation resulted in a complete resolution of symptoms. SIP is a
      common and severe adverse event (10%) in HT recipients treated with sirolimus.
      Drug discontinuation can dramatically improve clinical status. Previous lung
      injury may play a role in SIP pathogenesis.

PMID- 16962484
TI  - Graft-vs-host disease as a complication of lung transplantation.
AB  - We report a rare case of acute graft-vs-host disease (aGVHD) after a lung
      transplant. The patient presented with advanced disease manifested by skin rash,
      fever, diarrhea, liver dysfunction and severe pancytopenia. He went on to die of
      sepsis and multi-organ failure. aGVHD is a disease often confused with drug
      reactions or viral infection; therefore, it is important to have a high index of
      suspicion and to confirm the diagnosis early with tests for donor cell chimerism.
      Effective treatment is elusive but we are learning a great deal about the
      underlying mechanisms of this disease and hope to develop better treatment.

PMID- 16962485
TI  - Accrual issues in genitourinary cancer clinical trials.

PMID- 16962486
TI  - Treatment of intermediate-risk prostate cancer with brachytherapy without
      supplemental pelvic radiotherapy: a review of the H. Lee Moffitt Cancer Center
      experience.
AB  - PURPOSE: To determine the biochemical outcomes of patients with intermediate-risk
      prostate cancer treated at the H. Lee Moffitt Cancer Center with an I-125
      permanent seed implant without supplemental pelvic radiotherapy. METHODS AND
      MATERIALS: Under an institutional review board approved protocol, the charts of
      88 patients with intermediate-risk prostate cancer and a minimum follow-up of 36
      months treated with brachytherapy without supplemental pelvic radiotherapy were
      reviewed. Median follow-up for the whole cohort was 57 months (range 37-121).
      Biochemical failure was defined using the American Society for Therapeutic
      Radiology and Oncology definition. RESULTS: The 5-year biochemical failure-free
      survival for the cohort was 83%. Patients with perineural invasion had a worse
      biochemical outcome, which was statistically significant (perineural invasion vs.
      no perineural invasion, 5-year biochemical failure-free survival 64% vs. 89%, P =
      0.004). None of the following factors were found significant in this subset of
      patients: Gleason scores 6 versus 7, primary Gleason grades 3 versus 4,
      percentage of core positive <20% versus >20%, number of cores positive <2 versus
      2 versus >2, hormonal therapy versus no hormonal therapy, T1 versus T2, prostate
      specific antigen <10 versus >10, or > or =2 intermediate risk factors versus 1
      intermediate risk factor. CONCLUSIONS: Our data suggest that patients with
      intermediate-risk prostate cancer may be treated effectively with brachytherapy
      without supplemental pelvic radiotherapy. However, because of the limited nature
      of our study, we cannot exclude that patients with intermediate-risk prostate
      cancer may benefit from supplemental external beam radiotherapy.

PMID- 16962487
TI  - Risk of renal insufficiency in African-Americans after radical nephrectomy for
      kidney cancer.
AB  - PURPOSE: We conducted a retrospective review to evaluate the change in serum
      creatinine in an African-American population undergoing radical nephrectomy.
      MATERIALS AND METHODS: Race, and preoperative and follow-up creatinine data were
      extracted from the medical records of all patients who underwent radical
      nephrectomy performed by a single surgeon. Patients were classified as African
      American or black and non-African-American. The non-African-American group
      included Caucasian, Asian, and Hispanic patients. RESULTS: A total of 22 African
      American and 19 non-African-American patients were studied. Mean preoperative
      creatinine was 1.3 mg/dL in African-American patients and 1.1 in non-African
      American patients (P = 0.07). Average follow-up creatinine was 1.7 in the African
      Americans, with a mean change in creatinine of 0.4, compared to the non-African
      Americans, in which mean follow-up creatinine was 1.3 (P = 0.004) with a mean
      change of 0.2 (P = 0.048). Average follow-up creatinine was higher in African
      American hypertensive (2.0 mg/dl) compared with non-African-American hypertensive
      patients (1.4 mg/dl; P = 0.002). Average change in creatinine was also higher in
      African-American hypertensive versus non-African-American hypertensive patients
      (0.6 vs. 0.2 mg/dl, P = 0.048). There were no racial differences seen in
      normotensive cases. Average follow-up was 9.7 months for African-American and
      11.6 months for non-African-American patients. CONCLUSIONS: Our data indicate
      that race may be a significant risk factor for renal deterioration after radical
      nephrectomy.

PMID- 16962488
TI  - Reduced incidence of bony metastasis at initial prostate cancer diagnosis: data
      from CaPSURE.
AB  - PURPOSE: Despite stage migration as a result of screening, many individuals are
      diagnosed each year with metastatic (M+), as opposed to localized (M0), prostate
      cancer. This study describes features that characterize patients with M+ compared
      to those diagnosed with M0 disease. MATERIALS AND METHODS: Patients enrolled in
      the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a
      national, longitudinal registry of men with prostate cancer, formed the basis of
      this study. The prevalence, and changes with time, of patients with M+ and M0
      cancer by clinical and sociodemographic characteristics were examined. RESULTS:
      Of 10,113 patients diagnosed between 1990 and 2003, 266 (2.6%) had M+ disease at
      diagnosis. From 1990 to 1997, 4.2% of 4020 total patients had M+ versus 1.6% of
      6093 total patients diagnosed between 1998 and 2003 (odds ratio 0.34; 95%
      confidence interval 0.24-0.48; P < 0.0001). In univariate analysis, advanced age,
      higher prostate-specific antigen, Gleason grade, black race, lower income, and
      lower educational level were associated with M+ versus M0 disease (P < 0.01).
      However, in multivariate analysis, only higher serum prostate-specific antigen
      and higher Gleason grade, and not the sociodemographic variables, remained
      associated with M+ disease (P < 0.01). Patients with M+ diagnosed between 1998
      and 2003 are more likely to harbor high-grade (Gleason > or =8) primary tumors
      (62% vs. 45%, P = 0.02) than those diagnosed between 1990 and 1997. No changes in
      age, race, education, insurance status, or income were observed in the early
      versus late era. CONCLUSIONS: These findings show a reduction in the incidence of
      metastatic disease at initial prostate cancer diagnosis. Furthermore, biologic,
      rather than socioeconomic, factors are associated with this type of disease
      presentation.

PMID- 16962489
TI  - Complete response of bony metastatic bladder urothelial cancer to neoadjuvant
      chemotherapy and cystectomy.
AB  - We report on a 38-year-old male diagnosed with biopsy-proven bladder urothelial
      carcinoma metastatic to the bone, who had a complete response to neoadjuvant
      chemotherapy consisting of carboplatin and gemcitabine. The final pathology of
      his radical cystoprostatectomy revealed no residual cancer. The patient continues
      to be without evidence of disease 2 years postoperatively. This case shows that
      neoadjuvant chemotherapy with nonstandard regimens can yield responses in
      patients with bone metastases.

PMID- 16962490
TI  - A salutary tale of mistaken identity in testicular cancer.
AB  - This case report illustrates the importance of not relying on imaging alone. A 26
      year-old patient underwent an orchidectomy for mature teratoma; however, as he
      had abdominal lymphadenopathy, he was treated with 2 cycles of chemotherapy
      followed by retroperitoneal lymph node dissection. The abdominal histology
      revealed mature teratoma and he remained on intense surveillance. Three years
      later, computerized tomography (CT) indicated he had lung lesions and left hilar
      lymphadenopathy and, despite normal tumor markers, he was thought to have
      relapsed. He was treated with 2 cycles of second-line chemotherapy but there was
      no change in the lung lesions. He underwent a CT-guided biopsy which diagnosed
      sarcoidosis. He was kept under observation by the respiratory physicians and
      remains well. Sarcoidosis is commonly associated with lymphoma among other
      malignancies. In the Mayo series, they concluded there was a strong association
      between sarcoidosis and teratoma but cautioned against a causal relationship as
      both diseases are rare and found in the same age group. This case report reminds
      us to always consider the differential diagnoses, particularly if the imaging
      does not fit the rest of the clinical picture, and when in doubt obtain histology
      prior to treatment.

PMID- 16962491
TI  - 11C-acetate positron emission tomography for occult prostate cancer.
AB  - We report, to our knowledge previously not described, a case of occult prostate
      cancer, in which 11C-acetate positron emission tomography disclosed tumor
      manifestation after failure of conventional diagnostic procedures.

PMID- 16962493
TI  - Basic overview of current immunotherapy approaches in urologic malignancy.
AB  - The immune response to evolving prostate cancer is a complex and carefully
      orchestrated process. Such a response is initiated when immature dendritic cells
      take up and process tumor-associated antigens. These dendritic cells must then be
      activated in order to present peptides to helper (CD4) T cells. Cytolytic (CD8) T
      cells are next "licensed" to achieve full effector function by interacting with
      both antigen presenting cells and tumor-specific CD4 T cells. Finally, activated
      CD8 T cells traffic to sites of neoplasia and mediate killing by multiple
      mechanisms. This article provides a basic overview of these processes, and
      discusses the manner by which current clinical interventions seek to augment or
      initiate an antitumor immune response. Various compensatory mechanisms which
      serve to down-regulate an antitumor response are also examined.

PMID- 16962494
TI  - Granulocyte-macrophage colony-stimulating factor-transduced allogeneic cancer
      cellular immunotherapy: the GVAX vaccine for prostate cancer.
AB  - New approaches to therapeutics of advanced prostate cancer are urgently needed.
      GVAX (granulocyte-macrophage colony-stimulating factor [GM-CSF] gene transduced
      irradiated prostate cancer vaccine cells) offers the possibility that "host
      versus prostate cancer" immune responses can be generated in prostate cancer
      patients. Critical components involve the dendritic cell loading of candidate
      prostate cancer lymph node metastasis and candidate bone metastasis antigens
      derived from irradiated prostate cancer whole cells. GM-CSF acts at the
      vaccination site to enhance activation dendritic cells and antigen presentation
      to both the B-cell and T-cell arms of the immune system. GVAX preclinically-in
      both rat and transgenic prostate cancer models-has antitumor activity which has
      informed early clinical trial designs. Clinical investigations reviewed in this
      report suggest that vaccination is safe and immune tolerance can be broken
      against prostate cancer. Multi-institutional phase III investigation is currently
      underway to evaluate the impact of allogeneic prostate GVAX cellular
      immunotherapy on time to progression and overall survival in hormone refractory
      prostate cancer.

PMID- 16962495
TI  - Autologous renal cell cancer vaccines using heat shock protein-peptide complexes.
AB  - Investigations into the role of heat shock proteins (HSPs) in immune response
      have progressed well into a third decade, and indications of their use for the
      treatment of renal cell carcinoma (RCC) in the adjuvant setting will be revealed
      in the near future when a randomized phase III clinical trial is completed.
      Additional ongoing and planned randomized clinical trials will test the efficacy
      of HSP-based vaccines in more advanced stages of RCC. This review describes the
      compelling scientific rationale behind testing HSPs in RCC against the backdrop
      of other immunotherapeutic approaches in this indication.

PMID- 16962496
TI  - Immunotherapy for prostate cancer using prostatic acid phosphatase loaded antigen
      presenting cells.
AB  - Dendritic cells from patients with cancer are deficient in number and functional
      activity, leading to inadequate tumor immunosurveillance as a result of poor
      induction of T-cell antitumor responses. Loaded dendritic cell therapy is a
      vaccination strategy aimed at eliciting tumor antigen-specific, T-cell immune
      responses. Loaded dendritic cell therapy using prostatic acid phosphatase
      (APC8015; Provenge, Dendreon Corp., Seattle, WA) as an immunogen has shown a
      survival benefit in patients with metastatic hormone-refractory prostate cancer
      in a randomized phase III trial. This review will summarize the prostate cancer
      clinical trials using APC8015 and discuss the potential future role of APC8015 in
      prostate cancer treatment.

PMID- 16962497
TI  - Anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) immunotherapy for the treatment of
      prostate cancer.
AB  - Costimulatory pathway ligands and receptors can deliver either positive or
      negative signals to help determine the ultimate fate of activated T lymphocytes.
      Cytotoxic T lymphocyte antigen-4 (CTLA-4) represents one of the most extensively
      studied receptors in the costimulatory pathway and has recently been shown to
      function as a potent inhibitor of T cell-mediated immunity. T-cell expression of
      CTLA-4 indirectly facilitates tumor progression by restraining host antitumoral
      immunity. In contrast, administration of a monoclonal antibody to block CTLA-4
      function can alleviate restraints on T-cell activity to promote immune-mediated
      tumor regression. We review the preclinical and clinical experience with CTLA-4
      blockade as a promising immunotherapeutic approach to treat patients with
      advanced prostate cancer.

PMID- 16962498
TI  - Future directions for vaccine-based therapies.
AB  - During recent years, cancer vaccines have made encouraging progress toward
      becoming a clinically relevant form of biologic therapy. However, current vaccine
      approaches have shown only limited success in patients with cancer because of
      inadequate immune activation. Recent insights into the elements that regulate
      immune responsiveness have provided new opportunities to enhance the efficacy of
      cancer vaccines through multiple pathways that involve afferent and efferent arms
      of the immune system. This article presents a set of emerging strategies that
      have resulted from our recent efforts to boost tumor-associated antigen-specific
      immunity and improve patient outcome. These new insights represent important
      consideration for the design and development of more effective immunotherapies
      during the next decade.

PMID- 16962510
TI  - The art of assessing metronidazole toxicity.

PMID- 16962511
TI  - The limitations of pH monitoring for detecting gastroesophageal reflux.

PMID- 16962513
TI  - Endoscopy in Gynecology: Past, present, and future.

PMID- 16962514
TI  - Endoscopic surgery: a moment in time?

PMID- 16962516
TI  - GyneFix: a frameless intrauterine device.

PMID- 16962517
TI  - A large symptomatic leiomyoma of the round ligament.

PMID- 16962518
TI  - Presacral neurectomy for surgical management of pelvic pain associated with
      endometriosis: a descriptive review.
AB  - Pelvic pain associated with endometriosis is a common clinical problem. In
      approximately 20% of cases endometriosis-related pelvic pain is either minimally
      or not responsive to medical treatment; thus surgical treatment seems to be a
      valid option. The aim of this review is to describe presacral neurectomy surgical
      techniques, data regarding safety and efficacy of this procedure, its
      indications, and future research on its applications in clinical practice.

PMID- 16962519
TI  - Volume change of uterine myomas during pregnancy: do myomas really grow?
AB  - STUDY OBJECTIVE: To estimate changes in uterine myoma volume during pregnancy.
      DESIGN: Review of departmental electronic perinatal database and medical records.
      Canadian Task Force Classification II-3. SETTING: Obstetrical ultrasound unit in
      an academic tertiary care center. PATIENTS: One hundred-seven patients diagnosed
      with uterine myomas during pregnancy and who had two or more obstetrical
      ultrasounds in different periods of pregnancy. INTERVENTIONS: We analyzed the
      change in volume of uterine myomas between the first half of pregnancy (up until
      19 weeks), third quarter (20-30 weeks), and last quarter (31 weeks to term). The
      volume of largest uterine myoma was calculated using the formula Volume
      (mm3)=Pi/6x(length mm)x(width mm)x(height mm). MEASUREMENTS AND MAIN RESULTS: The
      mean age of the population was 31+/-6 years. Between the first and the second
      study periods, the percentage of uterine myomas that decreased in size was 55.1%
      (95% CI: 43-66), with a mean decrease in volume of 35%+/-4%; while the percentage
      of uterine myomas that enlarged was 44.9% (95% CI: 34-56), with a mean increase
      in volume of 69%+/-11%. Between the second and the third study periods, 75% (95%
      CI: 56-87) became smaller, with a mean decrease in volume of 30%+/-3%; while 25%
      (95% CI: 13-43) enlarged, with a mean increase in volume of 102%+/-62%.
      CONCLUSION: Contrary to common belief, we found that uterine myomas commonly
      decrease in volume over the course of pregnancy.

PMID- 16962520
TI  - Feasibility of laparoscopic extraperitoneal surgical staging for locally advanced
      cervical carcinoma in a gynecologic oncology fellowship training program.
AB  - STUDY OBJECTIVE: Feasibility of laparoscopic extraperitoneal surgical staging for
      locally advanced cervical carcinoma in a gynecologic oncology fellowship training
      program. DESIGN: Retrospective analysis (II-2) of all patients who underwent
      laparoscopic extraperitoneal surgical staging at Women and Children's Hospital
      for locally advanced cervical cancer between June 2002 and June 2005. SETTING:
      Gynecologic oncology fellowship training program at a University-County Hospital
      PATIENTS: Thirty-two patients with clinical stage IIB-IVA cervical carcinoma were
      identified. INTERVENTIONS: Laparoscopic extraperitoneal surgical staging for
      clinical stage IIB-IVA cervical cancer. MEASUREMENTS AND MAIN RESULTS: A total of
      32 cases of laparoscopic extraperitoneal surgical staging for locally advanced
      cervical cancer performed by fellows-in-training were identified. Fellows were
      first assistant surgeon in 10 cases, and operating surgeon in 22 cases. Each
      fellow was mentored an average of 5 cases as first assistant surgeon. As
      operating surgeon, all 22 fellow cases (100%) were successfully performed without
      conversion to laparotomy. Fellow mean operative time was 163 minutes. Fellow mean
      aortic nodal count was 14. Fellow mean blood loss was 42 mL. The mean hospital
      stay was 1.6 days. Overall, 2 patients (6.2%) experienced a complication from the
      procedure. Over one half (53%) of the patients reported a prior abdominal
      surgery. No lymphedema has been reported in patients who underwent laparoscopic
      extraperitoneal surgical staging with a median follow-up of 10 months. Surgical
      comorbidities such as hypertension, diabetes, and obesity were common in the
      study group. A steep surgical learning curve for the fellows was demonstrated by
      comparing mean operative times to academic year. Aortic nodal metastasis was
      detected in 25% of cases, and 14% were occult. CONCLUSIONS: It is feasible to
      teach laparoscopic extraperitoneal surgical staging to fellows-in-training. Our
      data suggest that by the end of training, fellows can become proficient with the
      procedure and are capable of surgical outcomes and complication rates comparable
      to reported literature.

PMID- 16962521
TI  - Fertility after treatment of Asherman's syndrome stage 3 and 4.
AB  - STUDY OBJECTIVE: To evaluate the efficacy of hysteroscopic adhesiolysis and
      subsequent fertility in patients with adhesions stage 3 and 4. DESIGN: A
      retrospective cohort study (Canadian Task Force classification II-2). SETTING: A
      tertiary referral center for hysteroscopic surgery. PATIENTS: Seventy-one
      patients with intrauterine permanent adhesions. INTERVENTIONS: Hysteroscopic
      surgery with monopolar energy (n=31) or bipolar energy (n=40). Uterine cavity
      with at least one free ostial area was restored after one (n=31), two (n=20),
      three (n=15), or four or more (n=5) surgical procedures RESULTS: Sixty-four
      patients were followed. Evaluation of the uterine cavity after surgery has been
      performed by hysteroscopy for all the patients. All patients had resumption of
      menses, except for two patients with a history of uterine artery embolization.
      Pregnancy index rate after the procedure was 28 (43.8%) of 64, and the live birth
      rate was 21 (32.8%) of 64. In patients 35 years of age or younger, 20 of 30
      (66.6%) conceived compared with 8 of 34 (23.5%) in patients older than 35 years
      (p=.01). Three patients had either hysterectomy (n=2) or hypogastric arteries
      ligation for placenta accreta with uneventful postoperative course. CONCLUSIONS:
      Hysteroscopic adhesiolysis can be performed for severe adhesions stage 3 and 4
      with safety and efficacy. Age is the main predictive factors of success: the
      pregnancies were at risk of abnormal placentation.

PMID- 16962522
TI  - The detection of ureteral injuries after hysterectomy.
AB  - STUDY OBJECTIVE: To identify the incidence and outcomes of ureteral injuries in
      patients undergoing hysterectomy, and to evaluate the effect of intraoperative
      cystoscopy and early postoperative ureteral jet ultrasonography. DESIGN:
      Retrospective comparative study (Canadian Task Force classification II-2).
      SETTING: Tertiary medical center. PATIENTS: Fifteen patients who experienced
      ureteral injuries while undergoing hysterectomy out of 4950 total patients during
      a 6-year period. INTERVENTIONS: All patients underwent hysterectomy, and
      intraoperative cystoscopy or early postoperative ureteral jet ultrasonography
      were used to evaluate ureteral integrity. MEASUREMENTS AND MAIN RESULTS: The
      incidence of ureteral injury recognized after hysterectomy was 0.32%, and all
      ureteral injuries occurred during laparoscopic hysterectomy. The initial
      detection of ureteral injury resulted from intraoperative cystoscopy in five
      patients, early postoperative ureteral jet ultrasonography in two patients, and
      signs and symptoms in eight patients. The patients whose injuries were detected
      by either intraoperative cystoscopy or early postoperative ureteral jet
      ultrasonography were diagnosed earlier (1.7 and 19.9 postoperative days,
      respectively; p<.01) and tended toward more conservative treatment (p=.119;
      OR=10; 95% CI 0.78-128.78) than those who were diagnosed based on signs and
      symptoms alone. CONCLUSIONS: Use of intraoperative cystoscopy or early
      postoperative ureteral jet ultrasonography leads to earlier diagnosis of
      posthysterectomy ureteral injury, thereby allowing for more conservative
      treatment.

PMID- 16962523
TI  - Validation of hysteroscopic view in cases of endometrial hyperplasia and cancer
      in patients with abnormal uterine bleeding.
AB  - STUDY OBJECTIVE: To validate hysteroscopic view with histology in cases of
      endometrial hyperplasia and cancer in patients with abnormal uterine bleeding
      (AUB) DESIGN: Retrospective study (Canadian Task Force classification II-3).
      SETTING: University teaching hospitals in Rio de Janeiro and Sao Paulo, and
      private office in Rio de Janeiro. PATIENTS: Four thousand and fifty-four patients
      with AUB in whom hysteroscopic views were complete and the histologic result was
      conclusive. INTERVENTION: Four thousand and fifty-four office hysteroscopies with
      complete views and conclusive histologic results. The material for histologic
      examination was obtained through biopsy of the lesion in an outpatient unit or
      through the resection of the entire lesion in patients who underwent surgery.
      Histology was considered the "gold standard" and compared with the hysteroscopic
      view. MEASUREMENTS AND MAIN RESULTS: In the histology of the 4054 examinations,
      613 (15.2%) were endometrial hyperplasia, and 105 (2.6%) were endometrial cancer.
      The most frequent hysteroscopic finding was endometrial polyps (31.2%). In
      endometrial hyperplasia, the sensitivity of the hysteroscopic view was 56.3% (95%
      CI 52.2%-60.2%), specificity was 89.1% (95% CI 88.0%-90.1%), positive predictive
      value (PPV) was 48.0% (95% CI 44.3%-51.7%), negative predictive value (NPV) was
      92.0% (95% CI 90.1%-92.9%), and accuracy was 72.7% (95% CI 70.7%-74.7%). Accuracy
      was defined as the proportion of correct results among the hysteroscopic
      examinations. In endometrial cancer, the sensitivity of the hysteroscopic view
      was 80.0% (95% CI 71.1%-87.2%), specificity was 99.5% (95% CI 99.2%-99.7%), PPV
      was 81.5% (95% CI 72.7%-88.5%), NPV was 99.5% (95% CI 99.2%-99.7%), and accuracy
      was 89.8% (95% CI, 85.9%-93.6%). In the 814 patients (20.0%) in whom the
      hysteroscopic view was normal, there were no false negatives for endometrial
      cancer; however, there were 37 (4.5%) false negatives for endometrial
      hyperplasia. In the histologic cases of endometrial cancer, 101 (96.2%)
      hysteroscopic views were compatible with cancer or hyperplasia (80.0% and 16.2%,
      respectively). Ninety-seven out of 103 hysteroscopic views with cancer findings
      (94.2%) had histologic diagnosis of cancer or hyperplasia (81.5% and 12.6%,
      respectively). CONCLUSION: It seems that even in face of good validity of
      hysteroscopic view for endometrial hyperplasia and cancer, histologic study is
      mandatory in the presence of any lesion as the hysteroscopic view cannot
      completely replace the histologic study in patients with AUB.

PMID- 16962524
TI  - A randomized blinded study of the incidence of postoperative nausea and vomiting
      in women after major gynecologic laparoscopic surgery.
AB  - STUDY OBJECTIVE: To estimate the incidence of postoperative nausea and vomiting
      (PONV) in women undergoing major gynecologic laparoscopic surgery with an
      expected surgical duration exceeding 1 hour and anticipated overnight
      hospitalization. DESIGN: Randomized, double-blind, placebo-controlled study.
      SETTING: This study was set at a university hospital. PATIENTS: One hundred forty
      female patients with an American Society of Anesthesiology (ASA) physical status
      I or II and scheduled for gynecologic inpatient laparoscopic surgery.
      INTERVENTIONS: Patients were randomly assigned to receive 1 mg granisetron (Group
      A, n=70), or saline solution (Group B, n=70) intravenously after induction of
      general anesthesia. MEASUREMENTS AND MAIN RESULTS: The endpoints were evaluated
      by the following parameters: the incidence of PONV, episodes of nausea, retching,
      vomiting, rescue antiemetics, and complete response. Patients were closely
      observed for 24 hours after administration of the study drug. The two groups were
      generally well balanced in terms of demographic variables. The surgical period
      was longer in the granisetron group compared with the saline solution group. The
      total incidence of PONV was 41/70 (59%) in patients who underwent inpatient
      gynecologic laparoscopic surgery when no prophylactic antiemetic was given.
      Administration of granisetron decreased the incidence of PONV (29/70 [41%] vs
      41/70 [59%], p<.05), the incidence of vomiting (18/70 [26%] vs 31/70 [44%],
      p<.05), and the proportions of patients requiring rescue antiemetics (14/70 [20%]
      vs 47/70 [67%], p<.01), but these results were not comparable to other studies.
      CONCLUSION: A long surgical period may have great impact on the PONV in women who
      undergo gynecologic laparoscopic surgery, which implies the need for skilled
      gynecologic laparoscopists.

PMID- 16962525
TI  - Mammary ductoscopy for the evaluation of nipple discharge and comparison with
      standard diagnostic techniques.
AB  - STUDY OBJECTIVE: To describe performance of breast duct endoscopy and compare the
      method with conventional diagnostic techniques. DESIGN: Canadian Task Force
      classification III. SETTING: Interdisciplinary Breast Unit of a university
      hospital. PATIENTS: Consecutive and unselected series of 15 female patients
      including 20 breasts with nipple discharge. INTERVENTIONS: Prospective data
      assessment on all patients with ductoscopy for nipple discharge between April
      2003 to April 2004. All preoperative (mammography, ultrasonography, nipple smear)
      and minimally invasive (galactography, fine needle aspiration cytologic study)
      diagnostics were evaluated and compared with ductoscopy. MEASUREMENTS AND MAIN
      RESULTS: Mammography on 20 breasts showed BI-RADS-I (5%), BI-RADS-II (50%), and
      BI-RADS-III (45%). Breast ultrasound scanning showed abnormalities, classified as
      BI-RADS-III equivalent lesions in all cases. Nipple smear showed in 69.2% a
      normal cytology and in most cases revealed a papilloma later (n=8/9). Unilateral
      galactography was performed in 46.7% who had spontaneous nipple discharge. Two
      galactography results were unremarkable, and open biopsy demonstrated 1 atypical
      ductal hyperplasia and papilloma. On 20 breasts of 15 women, 19 ductoscopies were
      successfully performed (95%). In 17 cases open biopsy followed ductoscopy, and 1
      ductal carcinoma in situ (DCIS), 3 atypical ductal hyperplasia (ADH), 1 ductal
      hyperplasia without atypias, and 12 ductal papillomas were found. CONCLUSION:
      Compared to nipple smear, the diagnostic value of ductoscopy in this study is
      superior but marginally inferior to galactography and highly specialized breast
      ultrasound scanning. Therefore ductoscopy needs to be evaluated on a larger
      scale, preferably in multicenter trials to further determine its potential and
      indications.

PMID- 16962526
TI  - Cavaterm thermal balloon endometrial ablation versus hysteroscopic endometrial
      resection to treat menorrhagia: the French, multicenter, randomized study.
AB  - STUDY OBJECTIVE: To compare the efficacy and safety of Cavaterm thermal balloon
      endometrial ablation with hysteroscopic endometrial resection. DESIGN:
      Multicenter randomized trial (Canadian Task Force classification I). SETTING:
      Departments of obstetrics and gynecology in French university hospitals.
      PATIENTS: Fifty-one women with menorrhagia unresponsive to medical treatment.
      INTERVENTIONS: Women were randomized to thermal destruction of the endometrium or
      to hysteroscopic endometrial resection. Women completed preoperative, 6-, and 12
      month postoperative pictorial charts to determine Higham blood loss scores and a
      satisfaction questionnaire. Operative time, discharge time, complication rate,
      and resumption of normal activities were evaluated for each group. MEASUREMENTS
      AND MAIN RESULTS: Amenorrhea rates were 36% (95% CI 19%-56%) and 29% (95% CI 8%
      51%) in the Cavaterm and the endometrial resection groups at 12 months,
      respectively (ns). Both treatments significantly reduced uterine bleeding. The
      median decrease in Higham score at 12 months was significantly higher in women
      treated by Cavaterm (377, range 108-1300) than in women treated by resection
      (255, range -82 to 555) (p=.006). A subsequent hysterectomy for recurrent
      bleeding was performed in 2 women, both previously treated by resection. The rate
      of women reporting good or excellent satisfaction was 89% (95% CI 72%-98%) in the
      Cavaterm group and 79% (95% CI 54%-94%) in the resection group at 12 months.
      Discharge time was significantly lower in women treated by Cavaterm, although
      postoperative pain at 1 hour was higher. There were no major complications in
      either group. CONCLUSIONS: Cavaterm thermal balloon ablation was as effective as
      hysteroscopic endometrial resection to treat menorrhagia, both resulting in a
      significant reduction in menstrual blood loss and high patient satisfaction.

PMID- 16962527
TI  - Laparoscopic findings, histopathologic evaluation, and clinical outcomes in women
      with chronic pelvic pain after hysterectomy and bilateral salpingo-oophorectomy.
AB  - STUDY OBJECTIVE: To laparoscopically evaluate the pelvis of patients with chronic
      pelvic pain after hysterectomy and bilateral salpingo-oophorectomy, to determine
      any associated factors to the pain. DESIGN: Retrospective cohort of patients with
      chronic pelvic pain after hysterectomy and bilateral salpingo-oophorectomy
      (Canadian Task Force Classification II-2). SETTING: University-affiliated
      teaching hospital. PATIENTS: From January 1990 through May 2002, 124 women with
      chronic pelvic pain after hysterectomy and bilateral salpingo-oophorectomy
      underwent laparoscopic and histopathologic evaluation of the pelvis.
      INTERVENTION: Diagnostic laparoscopy was performed to inspect the pelvis for any
      signs of pathology. If any abnormalities were visualized, they were treated with
      CO2 laser resection and sent for histopathologic evaluation. MAIN OUTCOME
      MEASURES: Laparoscopic and histopathologic findings of the pelvis, as well as
      subjective pain improvement after laparoscopy. CONCLUSION: The most common
      histopathologic findings at laparoscopy in women with chronic pelvic pain after
      hysterectomy and bilateral salpingo-oophorectomy included adhesions, adnexal
      remnants, and endometriosis. Laparoscopic treatment of any pelvic pathologic
      condition improved pain symptoms in these women.

PMID- 16962528
TI  - Clinical and quality-of-life outcomes after fertility-sparing laparoscopic
      surgery with bowel resection for severe endometriosis.
AB  - STUDY OBJECTIVE: To describe the effect of fertility-sparing laparoscopic
      excision of endometriosis and bowel resection on clinical and quality-of-life
      outcomes. DESIGN: Prospective observational cohort study (Canadian Task Force
      classification II-2). SETTING: Australian tertiary referral center for the
      surgical treatment of endometriosis. PATIENTS: Seven consecutive patients with
      known endometriosis involving the bowel. INTERVENTION: Laparoscopic resection of
      all endometriosis, including laparoscopic bowel resection with end-to-end
      anastomosis with or without temporary ileostomy. MEASUREMENTS AND MAIN RESULTS:
      Preoperative and 12-month postoperative data were collected by use of visual
      analogue scores for dysmenorrhea, nonmenstrual pelvic pain, dyspareunia, and
      dyschezia. Validated research tools (SF12, EuroQOL, and Sexual Activity
      Questionnaire) also assessed quality of life. Reduction in median pain scores at
      baseline was demonstrated and at 12 months after operation for dysmenorrhea 71
      (interquartile range 43-85) versus 5 (0-10); p=.028, nonmenstrual pelvic pain 74
      (48-85) versus 11 (0-18); p=.046, dyspareunia 66 (0-98) versus 5 (0-8); p=.080,
      and dyschezia 48 (20-64) versus 20 (0-40); p=.173. All measures of quality of
      life were improved at 12 months after surgery, although not reaching statistical
      significance because of the small sample size. All three women wishing to
      conceive after operation have been successful, resulting in three live births at
      term. There were few complications associated with this surgery. CONCLUSION:
      Fertility-sparing laparoscopic excision of endometriosis with bowel resection
      results in improvements in all aspects of pain and quality of life. Results
      appear to parallel published data for conservative resection of endometriosis not
      involving bowel. For women with severe endometriosis involving bowel, this
      surgical treatment provides a viable alternative to pelvic clearance and
      successfully maintains fertility.

PMID- 16962529
TI  - Laparoscopic resection of intestinal endometriosis: a 5-year experience.
AB  - STUDY OBJECTIVE: To describe the clinical manifestations, surgical techniques,
      and complications observed in patients undergoing laparoscopic resection of
      intestinal deeply infiltrating endometriosis (DIE). DESIGN: Prospective
      nonrandomized (Canadian Task Force Classification II-3). SETTING: University
      hospital and private practice. PATIENTS: We evaluated 125 patients with
      intestinal DIE treated from February 2000 through September 2005. INTERVENTIONS:
      Laparoscopic radical excision of DIE followed by resection of the rectosigmoid
      colon. MEASUREMENTS AND MAIN RESULTS: The clinical examination of our patients
      demonstrated that 66.4% of patients had tenderness, whereas 80.8% had nodules on
      the pouch of Douglas. In 95.2% we observed pain caused by cervical mobilization,
      and all the patients had pain during the pouch of Douglas mobilization. Regarding
      bowel infiltration, preoperative investigation with rectal endoscopic
      ultrasonography was positive in all cases. Endoscopic rectal ultrasonography
      demonstrated the depth of intestinal infiltration. Superficial lesions were
      observed in 9.6% of patients and muscularis involvement in 71.2%. The segmental
      resection was performed in most of the patients (92%) and the linear resection in
      6.4% of them. Median surgical time was 110 minutes, and the median hospital stay
      was 7 days after the surgery; the patients continued fasting for 3 to 7 days. The
      return to normal activity was achieved in a median 15 days after the surgery. The
      surgical procedure and the postoperative follow-up demonstrated no complications
      in 90.4% of the patients. Minor complications were observed in 4% of the cases.
      Major complications occurred in 5.6% of the patients, including 2 cases of
      intestinal fistulas (1.6%) and 3 cases of long-lasting urinary retention (2.4%).
      CONCLUSION: Clinical symptoms of patients with intestinal endometriosis are not
      specific. Operative laparoscopy is a safe and effective method to treat
      intestinal endometriosis. To avoid major complications, special attention must be
      paid to the intestinal anastomosis and to the nerve preservation.

PMID- 16962530
TI  - A comparative study of hysteroscopic sterilization performed in-office versus a
      hospital operating room.
AB  - STUDY OBJECTIVE: To compare hysteroscopic female sterilization procedures
      performed in-office versus a hospital operating room (OR) among newly trained
      physicians. DESIGN: Multisite hospital operating rooms and physician offices.
      PATIENTS: Women desiring permanent hysteroscopic sterilization. INTERVENTION:
      Hysteroscopic female sterilization with the Essure system. MEASUREMENTS AND MAIN
      RESULTS: Procedure time (scope in/scope out time), device placement rates, and
      incidence of complications and adverse events were compared. There was no
      significant difference in scope time between the 2 settings. There was no
      significant difference in placement rates, although the placement rate was
      somewhat higher in-office (91% vs 88%). There were no complications among any of
      the procedures, and the incidence of minor adverse events was extremely low in
      both settings (OR=2%, in-office=1%). CONCLUSION: There is no clear advantage to
      performing hysteroscopic sterilization in a hospital OR. Hysteroscopic
      sterilization can be performed safely and efficiently in an office setting.

PMID- 16962531
TI  - The use of lightly embalmed (fresh tissue) cadavers for resident laparoscopic
      training.
AB  - STUDY OBJECTIVE: The value of a cadaver training program in laparoscopic surgery
      has rarely been studied. As there is a dearth of cadaver training programs, it is
      important to evaluate them. The goal of this study was to estimate if our cadaver
      training program significantly and relatively rapidly taught residents
      laparoscopic surgical skills. DESIGN: Observational, timed comparative study
      (Canadian Task Force classification II-3). SETTING: University of Louisville
      School of Medicine, Fresh Tissue Laboratory, Louisville, KY. PARTICIPANTS: Twenty
      nine obstetric/gynecology residents (15 postgraduate year PGY 2 and 14 PGY 3)
      participated in the study. INTERVENTION: During 5 half days, we compared the
      performance of each postgraduate year (PGY) 2 and PGY 3 obstetric/gynecology
      resident to his or her own results on five outcome skills before and after
      training in lightly embalmed cadavers. The testing was performed at the beginning
      and at the end of the week so that all improvement was secondary only to the
      training experience with the cadaver. Residents were assessed using laparoscopic
      techniques in a physical-reality simulator for three outcomes: bead transfer
      time, number of beads transferred, and suturing time on a stuffed vinyl glove and
      in two specific areas of the cadaver pelvis, with one slightly more difficult
      than the other. Assessment of suturing time was made on the two distinct tasks
      using the embalmed cadavers. Although the number of residents was relatively
      small, it covered two levels for one year. MEASUREMENTS AND MAIN RESULTS: The
      residents were assessed on a simulator before and after laparoscopic surgical
      training on the cadaver. The median decrease in bead transfer time (task I,
      simulator) was 38.5 seconds (p=.02); 69% of the residents showed some reduction
      in time to complete this task. The median increase in the number of beads
      transferred (task II, simulator) was 2.5 beads (p=.0001); 72.4% of the residents
      transferred at least one more bead after training. The median decrease in suture
      time (task III, simulator) was 63.5 seconds (p=.001); 79.3% of the residents
      performed this task more quickly after training. The median decrease in suture
      time (task IV, cadaver) was 54.5 seconds (p=.001); 72.4% of the residents showed
      improved performance on this task after training. The median reduction in suture
      time (task V, cadaver) was 53.5 seconds (p<.001); 82.8% of the residents
      completed this task more quickly after training. CONCLUSIONS: This cadaver
      surgical training program appeared to significantly improve laparoscopic surgical
      techniques in PGY 2 and PGY 3 obstetric/gynecology residents in a relatively
      short time. This model teaches residents specific training in the handling and
      manipulation of tissue as well as practice in surgical techniques for adnexal
      surgery, pelvic dissection, laparoscopic hysterectomy, and dissection within the
      space of Retzius that is not possible with mechanical trainers.

PMID- 16962532
TI  - A randomized comparison of suturing techniques for episiotomy and laceration
      repair after spontaneous vaginal birth.
AB  - STUDY OBJECTIVE: To compare the continuous knotless technique of perineal repair
      with the interrupted method after spontaneous vaginal birth DESIGN: A randomized
      controlled trial. DESIGN CLASSIFICATION: Canadian Task Force Classification I.
      SETTING: This study was undertaken in a university hospital with more than 2200
      deliveries per year. The static population of this district includes a wide range
      of socioeconomic classes and is predominately white. PATIENTS: From May 1 to
      November 19, 2003, 214 primiparous women with a second-degree perineal tear or
      episiotomy were randomly allocated to either the continuous knotless technique
      (CKT; n=107) or the interrupted technique (IT; n=107) suturing method.
      INTERVENTIONS: The interrupted technique (IT) involves placing 3 layers of
      sutures whereas the continuous knotless technique (CKT) involves reapproximating
      vaginal trauma, perineal muscles, and skin with a loose, continuous, nonlocking
      technique. MEASUREMENTS AND MAIN RESULTS: The primary outcomes of the study were
      perineal pain (evaluated by visual analogue scale) at 48 hours and day 10 and
      dyspareunia 3 months after delivery. Secondary outcomes included suture removal,
      wound dehiscence, analgesia use up to 48 hours, and satisfaction with repair
      established at 3 and 12 months after childbirth. At day 10, 19 women had dropped
      out of the study. Significantly fewer women reported pain at 10 days with the CKT
      than with the IT (32.3% vs 60.4%; p<.001). Analgesia use up to 48 hours
      postpartum was less in the CKT group than in the IT group (33.6% vs 54.2%;
      p<.05). No difference was found in superficial dyspareunia at 3 months for the
      CKT versus the IT group. CONCLUSION: The use of a continuous knotless technique
      for perineal repair is associated with less short-term pain than techniques with
      interrupted sutures.

PMID- 16962533
TI  - A prospective comparison of morcellator and culdotomy for extracting of uterine
      myomas laparoscopically in nullipara.
AB  - We compare the removal of uterine myomas in 78 nulliparous women identified by
      ultrasound during laparoscopic myomectomy through culdotomy or by use of a power
      morcellator. Patients were divided into two groups. The culdotomy group was
      significantly longer. There were no significant differences in tumor size, total
      specimen weight, patient body weight, total operating time, blood loss, and
      postoperative stay between each group. Uterine myomas can be removed successfully
      through either port site in nullipara; however, because of reduced removal time,
      the power morcellator is preferred.

PMID- 16962534
TI  - Use of the NovaSure Impedance Controlled Endometrial Ablation System in patients
      with intracavitary disease: 12-month follow-up results of a prospective, single
      arm clinical study.
AB  - STUDY OBJECTIVE: To assess the safety and effectiveness of the NovaSure Impedance
      Controlled Endometrial Ablation System for the treatment of excessive uterine
      bleeding in premenopausal and postmenopausal women with intracavitary disease
      (polyps or myomas) up to 3 cm. DESIGN: Prospective, single-arm study. (Canadian
      Task Force Classification II-2.) SETTING: Academic medical center. PATIENTS: This
      clinical study was conducted in 65 women with menometrorrhagia with confirmed
      (type I and II) submucous myomas up to 3 cm with and without polyps.
      INTERVENTION: Patients were treated with the NovaSure System and received no
      hormonal or mechanical pretreatment to thin the endometrial lining or as a
      uterine pathologic condition shrinking agent. MEASUREMENTS AND MAIN RESULTS: All
      patients were diagnosed with intracavitary disease during office hysteroscopy.
      Patients completed menstrual questionnaires at the initial screening and at 1
      year after treatment. Twelve-month results demonstrated that the NovaSure System
      was effective in reducing excessive uterine blood loss. Success (defined as
      reduction to normal bleeding) was observed in 95% (95% CI: 86%-99%) of patients,
      with 69% (95% CI: 56%-80%) reporting amenorrhea at 1 year after treatment. The
      median treatment time (time of energy delivery) was 78 seconds (range 61-120
      seconds). All patients underwent the procedure under local or intravenous
      sedation. No intraoperative or postoperative adverse events were reported. There
      was a significant decrease in premenstrual symptoms and dysmenorrhea at 12 months
      after the procedure. Ninety-five percent (95% CI: 86%-99%) of patients were
      satisfied with the procedure. CONCLUSION: Clinical results of this study
      demonstrate that the NovaSure System is safe and effective in treatment of
      patients with menometrorrhagia caused by intracavitary disease up to 3 cm.

PMID- 16962535
TI  - Laparoscopic uterosacral uterine suspension: a minimally invasive technique for
      treating pelvic organ prolapse.
AB  - STUDY OBJECTIVE: To assess the surgical outcomes of laparoscopic uterosacral
      uterine suspension and describe the surgical technique. DESIGN: Retrospective
      chart review (Canadian Task Force classification II-3). SETTING: University
      tertiary medical center. PATIENTS: Twenty-three patients with symptomatic uterine
      prolapse and desire for uterine preservation who underwent surgical repair.
      INTERVENTION: Laparoscopic uterine uterosacral uterine suspension. MEASUREMENTS:
      Preoperative and postoperative evaluations were completed. The stage of pelvic
      organ prolapse was assessed using the ICS pelvic organ prolapse quantification
      (POP-Q) examination. Descriptive statistics and paired t testing were used for
      statistical analysis. RESULTS: Nineteen of 23 patients (82.6%) had preoperative
      prolapse stage 2 or greater. Nine patients (40.9%) had uterine prolapse beyond
      the hymen. After operation there were significant improvements in the stage of
      prolapse (2 vs 0, p<.01). The POP-Q scores for point C and D were significantly
      further away from the hymen after operation than compared with the preoperative
      values (-0.6 vs -7.8, and -5.0 vs -8.6; p<.01) respectively. There were no
      intraoperative complications. The estimated blood loss (mean+/-SD) was 111.5+/
      139.4 mL. The hospital stay (mean+/-SD) was 2.2+/-1.7 days. None of the patients
      had symptomatic prolapse during the mean follow-up of 15.9 months. CONCLUSION:
      Laparoscopic uterine suspension appears to be a safe and effective treatment
      option for uterine prolapse in patients who desire uterine preservation.

PMID- 16962536
TI  - A minimally invasive technique for management of the large adnexal mass.
AB  - STUDY OBJECTIVE: To describe our experience managing large pelvic masses through
      a minilaparotomy incision using a flexible, self-retaining wound retractor and
      exteriorized drainage by application of 2-octyl cyanoacrylate and a thin
      polyurethane membrane. DESIGN: Prospective nonrandomized trial (Canadian Task
      Force classification II-1). SETTING: Academic university hospital. PATIENTS: Ten
      women undergoing minilaparotomy for adnexal masses. INTERVENTIONS: After
      obtaining institutional review board approval, we identified 10 patients who
      underwent minilaparotomy for treatment of adnexal masses not thought to be
      amenable to laparoscopic surgical management and with clinical, radiographic, and
      laboratory evaluation consistent with a low probability of malignancy. Charts
      were reviewed and data collected. MEASUREMENTS AND MAIN RESULTS: The median mass
      size was 17.5 cm (range 9-30 cm), median incision length was 4.0 cm (range 3-5.5
      cm), median patient age was 29.5 years (range 19-41 years), median body mass
      index was 24.7 (range 19.4-30.7), median duration of surgery was 85 minutes
      (range 53-141 minutes). Blood loss was minimal in all cases and all patients were
      discharged on the day of surgery. There were no diagnoses of ovarian malignancy.
      Pathologic diagnoses included mature cystic teratomas, cystadenomas, and
      cystadenofibromas. There were no instances of intraabdominal leakage of cyst
      fluid. One patient required readmission for a postoperative ileus. CONCLUSION:
      Minimally invasive management is a reasonable alternative to traditional
      laparotomy in the setting of a large adnexal mass with low probability of
      malignancy. This technique allows adequate access and exposure while minimizing
      the risk of intraabdominal contamination, speeding patient recovery, and
      optimizing cosmetic results. Further, this approach can be converted to a
      laparoscopic staging procedure if a patient is found to have ovarian cancer.

PMID- 16962537
TI  - Disseminated intravascular coagulation after laparoscopic multiple myomectomy
      with use of icodextrin: a case report.
AB  - Uterine leiomyomas are by far the most common benign genital tumors. The
      prevalence rates vary from 20% to 50%. Myomectomy is a standard surgical
      treatment and is prescribed for patients who wish to preserve their fertility.
      The laparoscopic approach allows a shorter hospital stay, faster recovery, less
      intraoperative blood loss, less postoperative pain, and possibly fewer adhesions
      than abdominal myomectomy when performed by skilled surgeons. Myomectomy is
      associated with the risk of excessive blood loss and adhesions formation. Reports
      of disseminated intravascular coagulation complicating this type of surgery are
      rare, and no prior cases have been reported in the literature after the use of 4%
      icodextrin. Randomized trials support the use of absorbable adhesion barriers to
      reduce adhesion formation. A case of disseminated intravascular coagulation after
      laparoscopic multiple myomectomy with the use of 4% icodextrin solution is
      described.

PMID- 16962538
TI  - Experiences with a xenograft (acellular bovine collagen matrix) in gynecologic
      fistula repairs.
AB  - Urogenital fistulas are significant, though uncommon, complications of
      gynecologic surgery, and fistula repair can be a challenging surgery for even the
      most experienced gynecologist. An interposition xenograft (acellular bovine
      collagen matrix), derived from bovine pericardium, has been used to accomplish
      successful repairs. We report on five urogenital fistula cases in which an
      interposition xenograft was used in achieving a successful repair. The use of an
      interposition xenograft is a successful option in urogenital fistula repair.

PMID- 16962539
TI  - Tubal perforation by ESSURE microinsert: a tubal perforation?

PMID- 16962540
TI  - Tubal perforation by ESSURE microinsert: clearly not a tubal perforation but a
      cornual-uterine perforation.

PMID- 16962541
TI  - Correct terminology regarding total laparoscopic radical surgery means
      transection of the vagina and closure of the vaginal cuff laparoscopically.

PMID- 16962544
TI  - New technique to perform hysteroscopy in 'women with an intact hymen' is really
      just the vaginoscopic approach (no-touch technique).

PMID- 16962547
TI  - Relationship between antipyretic effects and cytokine levels in uncomplicated
      falciparum malaria during different treatment regimes.
AB  - We have previously shown that both chloroquine and paracetamol (acetaminophen)
      have antipyretic activity during treatment of acute uncomplicated Plasmodium
      falciparum malaria in children 1-4 years old. Here, we studied if this effect was
      accompanied by changes in plasma cytokine levels. The 104 children were treated
      with either chloroquine or sulfadoxine/pyrimethamine (SP) alone, SP+chloroquine
      or SP+paracetamol for 4 days. Cytokine levels were determined days 0, 2 and 3,
      body temperature every sixth hour until 72h and parasitemia once daily for 4
      days. At admission, body temperature correlated with levels of IL-10, IFN-gamma
      and IL-6, and parasitemia correlated with IL-10 and IL-6. Except for TNF-alpha
      and IL-1beta, where no significant effect was found, all cytokine levels (IL-10,
      IFN-gamma, IL-6, IL-12, IL-13, IL-18 and IL-4) decreased up to day 2 (p<0.05). IL
      6 levels continued to fall from days 2 to 3 (p<0.05), whereas increased levels
      were found for several cytokines (IL-12, IL-13, IL-18 and IL-1beta) (p<0.05). The
      antipyretic effects of chloroquine and paracetamol could not be related to any
      specific changes in the evaluated cytokine production or in Th1/Th2 or
      inflammatory/anti-inflammatory cytokine ratios. Alternative mechanisms for
      antipyretic effects and associations between fever and cytokine levels during
      uncomplicated P. falciparum malaria are therefore discussed.

PMID- 16962548
TI  - Thermofluor-based high-throughput stability optimization of proteins for
      structural studies.
AB  - Production of proteins well suited for structural studies is inherently difficult
      and time-consuming. Protein sample homogeneity, stability, and solubility are
      strongly correlated with the proteins' probability of yielding crystals, and
      optimization of these properties will improve success rates of crystallization.
      In the current study, we applied the thermofluor method as a high-throughput
      approach for identifying optimal protein formulation for crystallization. The
      method also allowed optimal stabilizing buffer compositions to be rapidly
      identified for each protein. Furthermore, the method allowed the identification
      of potential ligands, physiological or non-physiological, that can be used in
      subsequent crystallization trials. For this study, the thermally induced melting
      points were determined in different buffers as well as with additives for a total
      of 25 Escherichia coli proteins. Crystallization trials were set up together with
      stabilizing and destabilizing additives identified using thermofluor screening. A
      twofold increase in the number of crystallization leads was observed when the
      proteins were cocrystallized with stabilizing additives as compared with
      experiments without these additives. This suggests that thermofluor constitutes
      an efficient generic high-throughput method for identification of protein
      properties predictive of crystallizability.

PMID- 16962549
TI  - Chemical reduction of pterins to dihydropterins as substrates for enzymatic
      reactions.
AB  - Dihydropterins are important intermediates in various metabolic pathways,
      including the biosynthesis of tetrahydrofolate and tetrahydromethanopterin, a key
      coenzyme in the one-carbon metabolism of methanogenic Archaea. Some procedures
      for the reduction of pterins to dihydropterins may produce undesirable
      tetrahydropterin contaminants. This work describes a procedure for the rapid
      reduction of pterins to dihydropterins while minimizing tetrahydropterin
      production that may be particularly useful in producing substrates for enzyme
      reactions when the dihydropterin substrate cannot be purchased commercially.

PMID- 16962550
TI  - Development and comparison of nonradioactive in vitro kinase assays for NIMA
      related kinase 2.
AB  - NIMA (never in mitosis arrest)-related kinase 2 (Nek2) is a serine/threonine
      kinase required for centrosome splitting and bipolar spindle formation during
      mitosis. Currently, two in vitro kinase assays are commercially available: (i) a
      radioactive assay from Upstate Biotechnology and (ii) a nonradioactive
      fluorescence resonance energy transfer (FRET) assay from Invitrogen. However, due
      to several limitations such as radioactive waste management and lower
      sensitivity, a need for more robust nonradioactive assays would be ideal.
      Accordingly, we have developed four quantitative and sensitive nonradioactive
      Nek2 in vitro kinase assays: (i) a dissociation-enhanced lanthanide fluorescence
      immunoassay (DELFIA) using peptides identified from a physiologically relevant
      protein substrate, (ii) DELFIA using Nek2 itself, (iii) a homogeneous time
      resolved FRET assay termed LANCE, and (iv) A method of detecting phosphorylated
      products by HPLC. The DELFIA and LANCE assays are robust in that they generated
      more than 10-fold and 20-fold increases in signal-to-noise ratios, respectively,
      and are amenable to robotic high-throughput screening platforms. Validation of
      all four assays was confirmed by identifying a panel of small molecule ATP
      competitive inhibitors from an internal corporate library. The most potent
      compounds consistently demonstrated less than 100 nM activity regardless of the
      assay format and therefore were complementary. In summary, the Nek2 in vitro time
      resolved FRET kinase assays reported are sensitive, quantitative, reproducible
      and amenable to high-throughput screening with improved waste management over
      radioactive assays.

PMID- 16962551
TI  - Pharmacokinetics and tissue distribution of enrofloxacin and its metabolite
      ciprofloxacin in the Chinese mitten-handed crab, Eriocheir sinensis.
AB  - The pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin were
      investigated in the Chinese mitten-handed crab after a single intramuscular
      injection of enrofloxacin at 5.0mg/kg body weight. The tissue concentrations of
      enrofloxacin and ciprofloxacin were determined simultaneously by a high
      performance liquid chromatography (HPLC) method. The data were analyzed with
      Practical Pharmacokinetic Program 3P97. The highest average concentrations of
      enrofloxacin in liver, muscle, gill, and hemolymph were 3.93, 12.42, 16.73, and
      11.04 microg/g (ml), respectively. The elimination half-lives (t(1/2beta)) for
      enrofloxacin were 92.42, 64.86, 38.80, and 52.39 h, respectively. The AUC(0
      infinity) values for enrofloxacin were 304.80, 260.74, 288.30, and 269.24 microg
      h/ml, respectively. Ciprofloxacin could be detected in all four tissues. The
      respective values of main pharmacokinetics parameters Cmax, t(1/2beta), and AUC(0
      infinity) were 0.52 microg/g (ml), 38.38 h, and 35.06 microg h/ml for liver; 0.24
      microg/g (ml), 65.36 h, and 25.64 microg h/ml for muscle; 0.10 microg/g (ml),
      112.88 h, and 11.57 microg h/ml for gill; and 0.30 microg/g (ml), 93.33 h, and
      39.99 microg h/ml for hemolymph.

PMID- 16962552
TI  - Two-dimensional expression pattern analysis of protein kinases after separation
      by MicroRotofor/SDS-PAGE.

PMID- 16962553
TI  - Application of the DNA-specific dye EvaGreen for the routine quantification of
      DNA in microplates.

PMID- 16962554
TI  - A High-throughput two-phase partition assay to measure the activity of lipid
      metabolizing enzymes.
AB  - A new method to measure the activity of lipid-metabolizing enzymes is described.
      Subsequent to an enzymatic reaction, a two-phase system (organic/aqueous) is
      established by the addition of a phase partition scintillation fluid (PPSF). The
      PPSF serves as a scintillation fluid, a phase partition agent, and a
      carrier/separator of an organic-soluble radiolabeled reaction substrate or
      product. Applying an empirically derived set of conditions typically enhances the
      separation of substrate from product whereby one species is effectively
      solubilized in the PPSF. In situ partitioning of the radionuclide-containing
      organic/lipid phase from the aqueous phase occurs within individual wells of 96
      well or 384-well density PPSF-resistant microtiter plates without the requirement
      for multiple organic solvent extractions and aspirations, making this method
      applicable to high-throughput screening. The utility of this method for both
      kinetic characterization and high-throughput screening is demonstrated with
      acetyl-CoA carboxylase and fatty acid synthase.

PMID- 16962555
TI  - Study of human lung elastin degradation by different elastases using high
      performance liquid chromatography/mass spectrometry.
AB  - Elastin is a structural insoluble protein which gives elasticity to tissues and
      organs. Although its hydrophobic and highly cross-linked nature makes it a very
      durable polymer, degradation of elastin in relation with several pathological
      conditions, such as pulmonary emphysema, has been documented. Since different
      enzymes may be involved in elastolysis, it is of interest to determine which
      enzyme is responsible for the degradative effects observed in a certain disease.
      The aim of this work was to study elastin degradation by proteases from different
      families (serine, cysteine, and metalloproteases) using liquid chromatography
      coupled to mass spectrometry to characterize the elastin-derived peptides.
      Incubation of insoluble human elastin with different elastases revealed that,
      indeed, each protease degrades elastin in a preferential way giving rise to
      specific peptide patterns. This opens the possibility of using a given set of
      peptides as biomarkers for disease-related elastolysis.

PMID- 16962556
TI  - Exploring "one-shot" kinetics and small molecule analysis using the ProteOn XPR36
      array biosensor.
AB  - A ProteOn XPR36 parallel array biosensor was used to characterize the binding
      kinetics of a set of small molecule/enzyme interactions. Using one injection with
      the ProteOn's crisscrossing flow path system, we collected response data for six
      different concentrations of each analyte over six different target protein
      surfaces. This "one-shot" approach to kinetic analysis significantly improves
      throughput while generating high-quality data even for low-molecular-mass
      analytes. We found that the affinities determined for nine sulfonamide-based
      inhibitors of the enzyme carbonic anhydrase II were highly correlated with the
      values determined using isothermal titration calorimetry. We also measured the
      temperature dependence (from 15 to 35 degrees C) of the kinetics for four of the
      inhibitor/enzyme interactions. Our results illustrate the potential of this new
      parallel-processing biosensor to increase the speed of kinetic analysis in drug
      discovery and expand the applications of real-time protein interaction arrays.

PMID- 16962557
TI  - Magnetic-particles-based high-throughput genotyping method with dual-color
      fluorescence hybridization.

PMID- 16962558
TI  - Enolase takes part in a macromolecular complex associated to mitochondria in
      yeast.
AB  - In eucaryotes, glycolytic enzymes are classically regarded as being localised in
      the cytosol. Recently, we have shown that part of the cellular pool of the
      glycolytic enzyme, enolase, is tightly associated with the mitochondrial surface
      in the yeast Saccharomyces cerevisiae (N. Entelis, I. Brandina, P. Kamenski, I.A.
      Krasheninnikov, R.P. Martin and I. Tarassov, A glycolytic enzyme, enolase, is
      recruited as a cofactor of tRNA targeting toward mitochondria in Saccharomyces
      cerevisiae, Genes Dev. 20 (2006) 1609-1620). Here, using enzymatic assays, we
      show that all glycolytic enzymes are associated with mitochondria in yeast, to
      extents similar to those previously reported for Arabidopsis cells. Using
      separation of mitochondrial complexes by blue-native/SDS-PAGE and
      coimmunoprecipitation of mitochondrial proteins with anti-enolase antibodies, we
      found that enolase takes part in a large macromolecular complex associated to
      mitochondria. The identified components included additional glycolytic enzymes,
      mitochondrial membrane carriers, and enzymes of the TCA cycle. We suggest a
      possible role of the enolase complex in the channeling of pyruvate, the terminal
      product of glycolysis, towards the TCA cycle within mitochondria. Moreover, we
      show that the mitochondrial enolase-containing complex also contains the
      cytosolic tRNA(CUU)Lys, which is mitochondrially-imported, and its presumed
      import carrier, the precursor of the mitochondrial lysyl-tRNA synthetase. This
      suggests an unsuspected novel function for this complex in tRNA mitochondrial
      import.

PMID- 16962559
TI  - Structure and localization of an essential transmembrane segment of the proton
      translocation channel of yeast H+-V-ATPase.
AB  - Vacuolar (H+)-ATPase (V-ATPase) is a proton pump present in several compartments
      of eukaryotic cells to regulate physiological processes. From biochemical studies
      it is known that the interaction between arginine 735 present in the seventh
      transmembrane (TM7) segment from subunit a and specific glutamic acid residues in
      the subunit c assembly plays an essential role in proton translocation. To
      provide more detailed structural information about this protein domain, a peptide
      resembling TM7 (denoted peptide MTM7) from Saccharomyces cerevisiae (yeast) V
      ATPase was synthesized and dissolved in two membrane-mimicking solvents: DMSO and
      SDS. For the first time the secondary structure of the putative TM7 segment from
      subunit a is obtained by the combined use of CD and NMR spectroscopy. SDS
      micelles reveal an alpha-helical conformation for peptide MTM7 and in DMSO three
      alpha-helical regions are identified by 2D 1H-NMR. Based on these conformational
      findings a new structural model is proposed for the putative TM7 in its natural
      environment. It is composed of 32 amino acid residues that span the membrane in
      an alpha-helical conformation. It starts at the cytoplasmic side at residue T719
      and ends at the luminal side at residue W751. Both the luminal and cytoplasmatic
      regions of TM7 are stabilized by the neighboring hydrophobic transmembrane
      segments of subunit a and the subunit c assembly from V-ATPase.

PMID- 16962560
TI  - Driving fear and driving skills: comparison between fearful and control samples
      using standardised on-road assessment.
AB  - The present study explores driving skills in a group of 50 media-recruited
      driving-fearful and 50 control drivers, all of whom were women. Participants
      completed an on-road practical driving assessment with a professional driving
      instructor. Diagnostic as well as pre-post self-report and instructor driving
      assessments were conducted. Fearful drivers made more errors on the driving
      assessment than controls. However, the pattern of errors was identical for both
      groups, indicating that fear and anxiety may be associated with the number rather
      than the type of driving errors made. These differences remained when factors
      such as driving history, current driving frequency, and diagnosis were controlled
      using case selection. More research is needed to replicate the findings in more
      diverse samples. Additional work should also aim to clarify the specific role of
      driving skills in driving fear, which will facilitate treatment planning for
      exposure-based treatments and help identify cases where driving skills assessment
      may be appropriate.

PMID- 16962561
TI  - The classical srb4-138 mutant allele causes dissociation of yeast Mediator.
AB  - The Mediator complex is an essential co-activator for RNA polymerase II-dependent
      transcription in the budding yeast Saccharomyces cerevisiae. The S. cerevisiae
      core Mediator complex consists of three larger domains that are termed head,
      middle, and tail. The Med17 subunit is located within the head domain and is
      essential for cell viability. A temperature-sensitive allele of the MED17 gene
      known as srb4-138 causes all RNA polymerase II-dependent transcription to cease
      at the non-permissive temperature. The phenotype of srb4-138 allele has served as
      the main in vivo proof of the importance of Mediator, but the molecular basis for
      the effect of this mutant has not been determined. We here characterize Mediator
      from cells carrying the srb4-138 allele and find that the Mediator complex
      consistently breaks apart at the head/middle domain boundary even at lower
      temperatures. We find that both the head and middle domains are able to associate
      with the RNA polymerase independently of each other. Interestingly, both sub
      complexes are able to associate with an active promoter at the permissive
      temperature but at the non-permissive temperature the head domain is lost from
      the promoter.

PMID- 16962562
TI  - Neoplastic transformation and tumorigenesis associated with overexpression of
      IMUP-1 and IMUP-2 genes in cultured NIH/3T3 mouse fibroblasts.
AB  - Immortalization-upregulated protein 1 (IMUP-1) and immortalization-upregulated
      protein 2 (IMUP-2) genes have been recently cloned and are known to be involved
      in SV40-mediated immortalization. IMUP-1 and IMUP-2 genes were strongly expressed
      in various cancer cell lines and tumors, suggesting the possibility that they
      might be involved in tumorigenicity. To directly elucidate the functional role of
      IMUP-1 and IMUP-2 on neoplastic transformation and tumorigenicity, we stably
      transfected IMUP-1 and IMUP-2 into NIH/3T3 mouse fibroblast cells. Cellular
      characteristics of the neoplastic transformation were assessed by transformation
      foci, growth in soft agar, and tumor development in nude mice. We found that IMUP
      1 and IMUP-2 overexpressing cells showed altered growth properties, anchorage
      independent growth in soft agar and inducing tumor in nude mice. Furthermore,
      IMUP-1 and IMUP-2 transformants proliferated in reduced serum and shortened cell
      cycle. These results suggest that ectopic overexpression of IMUP-1 and IMUP-2 may
      play an important role in acquiring a transformed phenotype, tumorigenicity in
      vivo, and be related to cellular proliferation.

PMID- 16962563
TI  - Cell cycle-dependent regulation of kainate-induced inward currents in microglia.
AB  - Microglia are reported to have alpha-amino-hydroxy-5-methyl-isoxazole-4
      propionate/kainate (KA) types. However, only small population of primary cultured
      rat microglia (approximately 20%) responded to KA. In the present study, we have
      attempted to elucidate the regulatory mechanism of responsiveness to KA in GMIR1
      rat microglial cell line. When the GMIR1 cells were plated at a low density in
      the presence of granulocyte macrophage colony-stimulating factor, the
      proliferation rate increased and reached the peak after 2 days in culture and
      then gradually decreased because of density-dependent inhibition. At cell
      proliferation stage, approximately 80% of the GMIR1 cells exhibited glutamate
      (Glu)- and KA-induced inward currents at cell proliferation stage, whereas only
      22.5% of the cells showed responsiveness to Glu and KA at cell quiescent stage.
      Furthermore, the mean amplitudes of inward currents induced by Glu and KA at cell
      proliferation stage (13.8+/-3.0 and 8.4+/-0.6 pA) were significantly larger than
      those obtained at cell quiescent stage (4.7+/-0.8 and 6.2+/-1.2 pA). In the GMIR1
      cells, KA-induced inward currents were markedly inhibited by (RS)-3-(2
      carboxybenzyl) willardiine (UBP296), a selective antagonist for KA receptors. The
      KA-responsive cells also responded to (RS)-2-amino-3-(3-hydroxy-5-tert
      butylisoxazol-4-yl) propanoic acid (ATPA), a selective agonist for GluR5, in both
      GMIR1 cells and primary cultured rat microglia. Furthermore, mRNA levels of the
      KA receptor subunits, GluR5 and GluR6, at the cell proliferation stage were
      significantly higher than those at the cell quiescent stage. Furthermore, the
      immunoreactivity for GluR6/7 was found to increase in activated microglia in the
      post-ischemic hippocampus. These results strongly suggest that microglia have
      functional KA receptors mainly consisting of GluR5 and GluR6, and the expression
      levels of these subunits are closely regulated by the cell cycle mechanism.

PMID- 16962566
TI  - Bursting activity of neurons in the human anterior thalamic nucleus.
AB  - Single unit microelectrode recordings were obtained under local anesthesia in 5
      patients who underwent placement of deep brain stimulation electrodes in the
      anterior thalamic nucleus for control of intractable epilepsy. Of the 261 neurons
      recorded, 145 were in the anterior nucleus (AN), with the remainder ventral to AN
      in nucleus cucularis and dorsal dorsomedian nucleus (DM). 126 of the 261 neurons
      fired in bursts, and of these, 74 cells were analyzed in greater detail to
      characterize their bursting pattern. The bursts in 70% of the bursting neurons
      were characterized as low-threshold calcium spike (LTS) mediated bursts, on the
      basis of their intraburst firing pattern. The bursts of the remainder, although
      similar to LTS bursts, did not fulfil all of the criteria for an LTS burst and
      were termed atypical bursting cells. LTS and atypical bursting cells were found
      both within AN and in the nucleus cucularis and dorsal DM. The LTS bursting
      observed in these patients may be due to the altered electrophysiological state
      of the patients studied since LTS bursting in thalamus is usually only observed
      during sleep. This study describes for the first time the properties of this
      nucleus in humans and may be important in furthering our knowledge of thalamic
      mechanisms of epileptogenesis.

PMID- 16962565
TI  - Low affinity binding of the classical D1 antagonist SCH23390 in rodent brain:
      potential interaction with A2A and D2-like receptors.
AB  - Whereas structurally dissimilar D(1) antagonists competing for [(3)H]-SCH23390
      binding recognize primarily one site in striatum, two distinct affinity states
      are observed in both amygdala and hippocampus. The binding profile of SCH23390 is
      similar in both of these regions, with the high affinity site (K(D) approximately
      0.4 nM) consistent with D(1)/D(5) receptors. The appearance of the low affinity
      site (K(D) approximately 300 nM) is dependent upon the absence of MgCl(2), but
      independent of D(1) expression (i.e., still present in D(1) knockout mice).
      Although the density of high affinity state receptor is lower in hippocampus or
      amygdala of D(1) knockout mice, some residual binding remains, consistent with
      the known expression of D(5) receptors in these regions. Remarkably, in
      hippocampus, the affinity of the low affinity site is shifted rightward in the
      presence of the D(2) antagonist domperidone and is largely absent in the
      hippocampus of D(2) knockout animals. Additionally, this site is also shifted
      rightward in the presence of the A(2A) ligands SCH58261, CSC, or NECA, or in the
      absence of A(2A) receptors. The affinity of SCH23390 for this low affinity site
      is greater than seen for SCH23390 binding to D(2) receptors in heterologous
      expression systems, consistent with the hypothesis that both D(2) and A(2A)
      receptors are involved in the low affinity binding site. Therefore, we suggest
      that the heteromerization of D(2) and A(2A) receptors reported previously in
      vitro also may occur in the brain of both rats and mice.

PMID- 16962564
TI  - Maternal separation alters drug intake patterns in adulthood in rats.
AB  - Maternal separation/handling (MS/H) is an animal model of early life stress that
      causes profound neurochemical and behavioral alterations in pups that persist
      into adulthood. Many recent studies have used the MS/H model to study changes in
      drug effects in adulthood that are linked to behavioral treatments and stressors
      in the perinatal period. The drug effects focused on in this review are the
      reinforcing properties of the abused drugs, cocaine and alcohol. A striking
      finding is that variations in maternal separation and handling cause changes in
      ethanol and cocaine self-administration. Further, these changes indicate that
      various manipulations in the perinatal period can have long lasting effects of
      interest to biochemical pharmacologists. This article will review recent studies
      on ethanol and cocaine self-administration using the MS/H model and the
      neurochemical alterations that may play a role in the effects of MS/H on ethanol
      and cocaine self-administration. Studying the MS/H model can provide important
      clues into the vulnerability to drug abuse and perhaps identify a crucial window
      of opportunity for therapeutic intervention.

PMID- 16962567
TI  - Auditory semantic networks for words and natural sounds.
AB  - Does lexical processing rely on a specialized semantic network in the brain, or
      does it draw on more general semantic resources? The primary goal of this study
      was to compare behavioral and electrophysiological responses evoked during the
      processing of words, environmental sounds, and non-meaningful sounds in
      semantically matching or mismatching visual contexts. A secondary goal was to
      characterize the dynamic relationship between the behavioral and neural
      activities related to semantic integration using a novel analysis technique, ERP
      imaging. In matching trials, meaningful-sound ERPs were characterized by an
      extended positivity (200-600 ms) that in mismatching trials partly overlapped
      with centro-parietal N400 and frontal N600 negativities. The mismatch word-N400
      peaked later than the environmental sound-N400 and was only slightly more
      posterior in scalp distribution. Single-trial ERP imaging revealed that for
      meaningful stimuli, the match-positivity consisted of a sensory P2 (200 ms), a
      semantic positivity (PS, 300 ms), and a parietal response-related positivity (PR,
      500-800 ms). The magnitudes (but not the timing) of the N400 and PS activities
      correlated with subjects' reaction times, whereas both the latency and magnitude
      of the PR was correlated with subjects' reaction times. These results suggest
      that largely overlapping neural networks process verbal and non-verbal semantic
      information. In addition, it appears that semantic integration operates across
      different time scales: earlier processes (indexed by the PS and N400) utilize the
      established meaningful, but not necessarily lexical, semantic representations,
      whereas later processes (indexed by the PR and N600) are involved in the explicit
      interpretation of stimulus semantics and possibly of the required response.

PMID- 16962568
TI  - Activation of the central cholinergic system mediates the reversal of hypotension
      by centrally administrated U-46619, a thromboxane A2 analog, in hemorrhaged rats.
AB  - In the present study, we investigated the role of the central cholinergic system
      in mediating the pressor effect of intracerebroventricularly administrated U
      46619, a thromboxane A2 (TxA2) analog, in hemorrhaged hypotensive rats.
      Hemorrhage was performed by withdrawing a total volume of 2.1 ml of blood per 100
      g body weight over a period of 10 min. Intracerebroventricular (i.c.v.) injection
      of U-46619 (0.5, 1, 2 micro g) produced a dose- and time-dependent increase in
      arterial pressure and reversed the hypotension of this condition. Hemorrhage
      caused small increases in extracellular hypothalamic acetylcholine and choline
      levels. Intracerebroventricular administration of U-46619 (1 micro g) further
      increased the levels of extracellular acetylcholine and choline by 57% and 41%,
      respectively. Pretreatment with SQ-29548 (8 mug; i.c.v.), a selective TxA2
      receptor antagonist, completely abrogated the effects of subsequent injection of
      U-46619 (1 mug; i.c.v.) on arterial pressure and extracellular acetylcholine and
      choline levels. Pretreatment with mecamylamine (50 micro g; i.c.v.), a
      cholinergic nonselective nicotinic receptor antagonist, attenuated the pressor
      effect of U-46619 (1 micro g, i.c.v.) in hemorrhaged rats whereas pretreatment
      with atropine (10 micro g; i.c.v.), a cholinergic nonselective muscarinic
      receptor antagonist, had no effect. Interestingly, pretreatment of rats with
      methyllycaconitine (10 micro g; i.c.v.) or alpha-bungarotoxin (10 micro g;
      i.c.v.), selective antagonists of alpha-7 subtype nicotinic acetylcholine
      receptors (alpha7nAChRs), partially abolished the pressor effect of U-46619 (1
      micro g; i.c.v.) in the hypotensive condition. Pretreatment with a combination of
      mecamylamine plus methyllycaconitine or mecamylamine plus alpha-bungarotoxin
      attenuated the reversal effect of U-46619, but only to the same extent as
      pretreatment with either antagonist alone. In conclusion, i.c.v. administration
      of U-46619 restores arterial pressure and increases posterior hypothalamic
      acetylcholine and choline levels by activating central TxA2 receptors in
      hemorrhaged hypotensive rats. The activation of central nicotinic cholinergic
      receptors, predominantly alpha7nAChRs, partially acts as a mediator in the
      pressor responses to i.c.v. injection of U-46619 under these conditions.

PMID- 16962569
TI  - Grape juice causes endothelium-dependent relaxation via a redox-sensitive Src-
      and Akt-dependent activation of eNOS.
AB  - OBJECTIVES: An enhanced endothelial formation of nitric oxide (NO) and
      endothelium-derived hyperpolarizing factor (EDHF), is thought to contribute to
      the protective effect of moderate consumption of red wine on coronary diseases.
      The present study has characterized endothelium-dependent relaxations to Concord
      grape juice (CGJ), a non-alcoholic rich source of grape-derived polyphenols, in
      the coronary artery. METHODS: Porcine coronary artery rings were suspended in
      organ chambers for the measurement of changes in isometric tension in the
      presence of indomethacin. NO formation was assessed by electron spin resonance
      spectroscopy, and the phosphorylation of Src, Akt and endothelial NO synthase
      (eNOS) by Western blot analysis in cultured endothelial cells. RESULTS:
      Endothelium-dependent relaxations to CGJ were slightly but significantly reduced
      by L-NA, not affected by charybdotoxin (CTX) plus apamin (APA, two inhibitors of
      EDHF-mediated responses) whereas the combination of L-NA, CTX plus APA reduced
      maximal relaxation to about 50%. In the presence of CTX plus APA, relaxations to
      CGJ were markedly reduced by the membrane permeant mimetic of superoxide
      dismutase (SOD), MnTMPyP, the membrane permeant analogue of catalase
      polyethyleneglycol-catalase (PEG-catalase), PP2, an inhibitor of Src kinase, and
      by wortmannin, an inhibitor of the PI3-kinase. CGJ stimulated the formation of
      reactive oxygen species and the N(omega)-nitro-L-arginine-, PP2- and wortmannin
      sensitive formation of NO in endothelial cells. The formation of NO was
      associated with a redox-sensitive and time-dependent phosphorylation of Src, Akt
      and eNOS. CONCLUSIONS: CGJ induces endothelium-dependent relaxations of coronary
      arteries, which involve a NO-mediated component and also, to a minor extent, an
      EDHF-mediated component. In addition, CGJ-induced NO formation is due to the
      redox-sensitive activation of Src kinase with the subsequent PI3-kinase/Akt
      dependent phosphorylation of eNOS.

PMID- 16962570
TI  - Analysis of the most highly cited articles from the 50-year history of CCA.
AB  - BACKGROUND: The 50th anniversary of CCA in 2006 prompted analysis of the most
      highly cited articles from the Journal's history. METHODS: Lists of most highly
      cited CCA articles were obtained from Current Contents (1974, 1991) and CCA
      (2006); all based on the ISI/Thomson Scientific database. PubMed search
      identified country of origin. RESULTS: Distribution of the most highly cited CCA
      articles was skewed towards those with high total citations. From the beginning,
      these articles originated from a diverse group of countries. This diversity
      increased with time to include countries from 4 continents. The most highly cited
      articles emerged at least 8-16 years following their publication. During the
      first 35 years of the Journal, there was a significant positive correlation
      between the total number of citations and the publication date of cited articles.
      Initially, virtually all most highly cited articles were methods papers, whereas
      during the past 25 years less than half of them reported methods; clinical
      research papers and reviews making up the rest. CONCLUSIONS: Results of this
      analysis may help in editorial policy-making and marketing of the Journal and in
      assessing the impact of individual countries on the field, and may guide authors'
      decision in submitting articles to the Journal.

PMID- 16962571
TI  - Pediatric reference intervals for lipids and apolipoproteins on the VITROS 5,1 FS
      Chemistry System.
AB  - OBJECTIVES: Lipid biomarkers are integral in the assessment of dyslipidemia and
      cardiovascular risk, conditions that have become increasingly prevalent in
      pediatric populations. A comprehensive set of pediatric reference intervals for
      traditional or recently established lipid analytes is not currently available.
      DESIGN AND METHODS: 525 outpatient samples from a pediatric population were
      categorized into five age groups ranging from 0 to 20 years of age. Groups were
      further partitioned by gender. Serum or plasma samples were analyzed on the
      VITROS 5,1 FS Chemistry System for cholesterol and triglycerides by dry-film
      methods, direct HDL-C and LDL-C by selective detergent elimination, and
      apolipoproteins AI and B by immunoturbidimetry. Reference intervals were
      established by non-parametric methods at the 2.5th and 97.5th percentiles.
      RESULTS: Lipid levels show age- and gender-related differences, particularly
      during the first year of life and in young adults following puberty.
      Concentrations of total cholesterol, LDL-C, and apo B were lowest in the 12
      months after birth and remained relatively constant throughout childhood, but
      decreased for males in early adulthood. Triglyceride levels increased gradually
      throughout childhood and adolescence, and along with cholesterol, the upper
      limits of these intervals exceeded the recommended concentrations of lipid levels
      in children. For HDL-C and apo AI, no age- or sex-related differences were found
      until after puberty when values for males decreased slightly. CONCLUSIONS: Our
      current reference intervals in children and adolescents provide an important
      update for lipid markers and suggest earlier incidence of hypercholesterolemia
      when compared to previous ranges. Increased profiling of lipids is anticipated,
      and these will aid in the early assessment of cardiovascular risk in pediatric
      populations.

PMID- 16962572
TI  - Simulation of nasal flow by lattice Boltzmann methods.
AB  - The lattice Boltzmann method is used to calculate the incompressible, viscous
      flow of air through a model of a nasal cavity, used in experiments. Computations
      are performed for steady flows at the inspiration and expiration phase of nose
      breathing. Computed pressure distributions and friction coefficients compare well
      with Navier-Stokes solutions from a finite-volume method on structured,
      curvilinear grids. The comparison with conventional Navier-Stokes solvers shows
      several advantages of the lattice Boltzmann method in particular for bio-medical
      flow problems. These are the fast grid generation, the simple, granular
      algorithm, suited for efficient parallelization and the high flexibility for
      implementing complex boundary conditions and additional transport equations.
      Lattice Boltzmann methods are therefore efficient candidates for fast flow
      predictions in the frame of computer-aided rhino-surgery.

PMID- 16962573
TI  - Complementation rescue of Pdx1 null phenotype demonstrates distinct roles of
      proximal and distal cis-regulatory sequences in pancreatic and duodenal
      expression.
AB  - The unique, well-demarcated expression domain of Pdx1 within the posterior
      foregut suggests that investigating its transcriptional regulation will provide
      insight into mechanisms that regionally pattern the endoderm. Previous
      phylogenetic comparison identified conserved noncoding regions that stimulate
      transcriptional activity selectively in cultured pancreatic beta cells.
      Characterization of these regulatory elements is helping to dissect the
      transcription factor networks that operate within beta cells, which is important
      for understanding the etiology of beta cell dysfunction and diabetes, as well as
      for developing methods to produce beta cells in vitro for cell-based therapies.
      We recently reported that deletion of three proximally located conserved areas
      (Area I-II-III) from the endogenous Pdx1 locus resulted in severely reduced
      expression of Pdx1 in the pancreas, and a milder decrease in other foregut
      tissues. Here, we report transgene-based complementation experiments on Pdx1 null
      mice, which reveal that the proximal promoter/enhancer region, including Area I
      II-III, rescues the pancreatic defects caused by Pdx1 deficiency, but only weakly
      promotes expression of Pdx1 in the postnatal stomach and duodenum. These results
      reveal a role for distal cis-regulatory elements in achieving the correct level
      of extra-pancreatic Pdx1 expression, which is necessary for the production of
      duodenal GIP cells and stomach gastrin cells.

PMID- 16962574
TI  - Tissue remodeling during maturation of the Drosophila wing.
AB  - The final step in morphogenesis of the adult fly is wing maturation, a process
      not well understood at the cellular level due to the impermeable and refractive
      nature of cuticle synthesized some 30 h prior to eclosion from the pupal case.
      Advances in GFP technology now make it possible to visualize cells using
      fluorescence after cuticle synthesis is complete. We find that, between eclosion
      and wing expansion, the epithelia within the folded wing begin to delaminate from
      the cuticle and that delamination is complete when the wing has fully expanded.
      After expansion, epithelial cells lose contact with each other, adherens
      junctions are disrupted, and nuclei become pycnotic. The cells then change shape,
      elongate, and migrate from the wing into the thorax. During wing maturation, the
      Timp gene product, tissue inhibitor of metalloproteinases, and probably other
      components of an extracellular matrix are expressed that bond the dorsal and
      ventral cuticular surfaces of the wing following migration of the cells. These
      steps are dissected using the batone and Timp genes and ectopic expression of
      alphaPS integrin, inhibitors of Armadillo/beta-catenin nuclear activity and
      baculovirus caspase inhibitor p35. We conclude that an epithelial-mesenchymal
      transition is responsible for epithelial delamination and dissolution.

PMID- 16962575
TI  - Voltage-dependent calcium influx mediates maturation of myofibril arrangement in
      ascidian larval muscle.
AB  - Calcium signaling is important for multiple events during embryonic development.
      However, roles of calcium influx during embryogenesis have not been fully
      understood since routes of calcium influx are often redundant. To define roles of
      voltage-gated calcium channel (Cav) during embryogenesis, we have isolated an
      ascidian Cav beta subunit gene (TuCavbeta) and performed gene knockdown using the
      morpholino antisense oligonucleotide (MO). The suppression of Cav activity by
      TuCavbetaMO remarkably perturbed gastrulation and tail elongation. Further,
      larvae with normal morphology also failed to exhibit motility. Phalloidin
      staining showed that arrangement of myofibrils was uncoordinated in muscle cells
      of TuCavbetaMO-injected larvae with normal tail. To further understand the roles
      of Cav activity in myofibrillogenesis, we tested pharmacological inhibitions with
      ryanodine, curare, and N-benzyl-p-toluensulphonamide (BTS). The treatment with
      ryanodine, an intracellular calcium release blocker, did not significantly affect
      the motility and establishment of the myofibril orientation. However, treatment
      with curare, an acetylcholine receptor blocker, and BTS, an actomyosin ATPase
      specific inhibitor, led to abnormal motility and irregular orientation of
      myofibrils that was similar to those of TuCavbetaMO-injected larvae. Our results
      suggest that contractile activation regulated by voltage-dependent calcium influx
      but not by intracellular calcium release is required for proper arrangement of
      myofibrils.

PMID- 16962576
TI  - Inhibition of the Na+ -K+ -2Cl- -cotransporter in choroid plexus attenuates
      traumatic brain injury-induced brain edema and neuronal damage.
AB  - The present study was aimed to elucidate the possible role of Na+ -K+ -2Cl- 
      cotransporter (NKCC1) on traumatic brain injury-induced brain edema, cerebral
      contusion and neuronal death by using traumatic brain injury animal model.
      Contusion volume was verified by 2,3,5,-triphenyltetrazolium chloride monohydrate
      staining. NKCC1 mRNA expression was detected by RT-PCR and the protein expression
      of NKCC1 was measured by Western blot. We found that the expression of NKCC1 RNA
      and protein were up-regulated in choroid plexus apical membrane from 2 h after
      traumatic brain injury, peaked at 8 h, and lasted for 24 h. Rats in the
      experimental group displayed severe brain edema (water content: 81.45 +/- 0.32%
      compared with 78.38 +/- 0.62% of sham group) and contusion volume significantly
      increased 8 h after traumatic brain injury (864.14 +/- 28.07 mm3). Administration
      of the NKCC1 inhibitor bumetanide (15 mg/kg, I.V.) significantly attenuated the
      contusion volume (464.03 +/- 23.62 mm3) and brain edema (water content: 79.12 +/-
      0.28%) after traumatic brain injury. Our study demonstrates that NKCC1
      contributes to traumatic brain injury-induced brain edema and neuronal damage.

PMID- 16962577
TI  - The proconvulsant effects of the GABAA alpha5 subtype-selective compound RY-080
      may not be alpha5-mediated.
AB  - RY-080 (ethyl 8-ethynyl-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5
      a][1,4]benzodiazepine-3-carboxylate) is an imidazobenzodiazepine with 40-50-fold
      higher affinity for the benzodiazepine binding site of alpha5- rather than alpha1
      , alpha2- or alpha3-containing GABAA receptors. Previous data describing RY-080
      as being convulsant suggests that inverse agonists selective for the alpha5
      subtype may not be suitable for clinical development. In the present study, we
      show that RY-080 possesses inverse agonism for the alpha1 and alpha5 subtypes of
      human recombinant GABAA receptors and whilst not convulsant it was proconvulsant.
      Hence, with pentylenetetrazole alone, the dose predicted to give tonic
      convulsions in 50% of the mice (ED50) was 108 mg/kg whereas in the presence of 1
      and 10 mg/kg RY-080, the ED50s were 93 and 57 mg/kg, respectively. In vivo [3H]L
      655,708 and [3H]Ro 15-1788 binding assays showed that the subtype selectivity of
      RY-080 in vivo was 7-10-fold for alpha5-relative to alpha1- and alpha2/alpha3
      containing receptors (respective ID50 values of 0.93, 9.7 and 6.2 mg/kg) and is
      therefore much lower than seen in vitro. Consequently, it is not possible to
      define a dose of RY-080 which gives high occupancy of the alpha5 subtype without
      binding to other subtypes and accordingly the proconvulsant effects of RY-080
      cannot be attributed solely to the alpha5 subtype.

PMID- 16962578
TI  - Modulation of agmatine on calcium signal in morphine-dependent CHO cells by
      activation of IRAS, a candidate for imidazoline I1 receptor.
AB  - The present study investigated the effects of agmatine action on imidazoline I1
      receptor antisera-selected protein (IRAS), a candidate for imidazoline I1
      receptor, on prolonged morphine-induced adaptations of calcium signal and long
      lasting alterations in gene expression to further elucidate the role of IRAS in
      opioid dependence. Two cell lines, Chinese hamster ovary cells expressing mu
      opioid receptor alone (CHO-mu) and expressing mu opioid receptor and IRAS
      together (CHO-mu/IRAS), were used. After chronic treatment with morphine for 48
      h, naloxone induced a significant elevation of intracellular calcium
      concentration ([Ca2+]i) in CHO-mu and CHO-mu/IRAS cells. Agmatine (0.01-3 microM)
      concentration-dependently inhibited the naloxone-precipitated [Ca2+]i elevation
      when co-pretreated with morphine in CHO-mu/IRAS, but not in CHO-mu. Efaroxan, an
      imidazoline I1 receptor-preferential antagonist, completely reversed the effect
      of agmatine in CHO-mu/IRAS. Agmatine (1-10 microM) administration after chronic
      morphine exposure for 48 h partially decreased the [Ca2+]i elevation in CHO
      mu/IRAS which was entirely antagonized by efaroxan, but not in CHO-mu. In
      addition, agmatine (1 microM) co-pretreated with morphine attenuated the naloxone
      precipitated increases of cAMP-responsive element binding protein and
      extracellular signal-regulated kinase 1/2 phosphorylations and c-Fos expression
      in CHO-mu/IRAS. These effects were blocked by efaroxan as well. Taken together,
      these results indicate that the agmatine-IRAS action system attenuates the up
      regulations of Ca2+ signal and its downstream gene expression in morphine
      dependent model in vitro, providing additional evidence to support the
      contribution of IRAS to opioid dependence.

PMID- 16962579
TI  - Hypotonic shock stimulates ascorbate release from coronary artery endothelial
      cells by a Ca2+ -independent pathway.
AB  - In endothelial cells, anion channels open upon osmotic swelling during shear
      stress and hypotonic shock. Therefore, we examined the effects of hypotonic shock
      on release of the antioxidant anion ascorbate from pig coronary artery
      endothelial cells. Hypotonic shock potentiated ascorbate release from freshly
      isolated or cultured pig coronary artery endothelial cells; subsequently cultured
      endothelial cells were used. The hypotonic shock-induced increase in Asc release
      was rapid, depended on the degree of hypotonic shock, and not due to membrane
      leakiness. Stimulating P2Y2 like receptors in endothelial cells with ATP causes
      ascorbate release via a Ca2+ -mediated pathway. Hypotonic shock-induced release
      differed from the Ca2+-mediated Asc release because: (a) the increase in release
      with hypotonic shock was additive to that with ATP or A23187 (Ca2+ -ionophore),
      (b) apyrase, suramin or removing extracellular Ca2+ did not affect the hypotonic
      shock-stimulated release, (c) anion channel blockers inhibited the release by the
      two pathways differently, and (d) hypotonic shock increased the ascorbate release
      from endothelial cells and cultured smooth muscle cells whereas the Ca2+ 
      mediated ascorbate release occurred only in endothelial cells. Accumulation of
      ascorbate by endothelial cells was examined at extracellular ascorbate
      concentrations of 10 (Na+ -ascorbate symporter not saturated) and 5000 microM
      (Na+ -ascorbate symporter saturated). Hypotonic shock and A23187 decreased
      ascorbate accumulation at 10 microM ascorbate but increased it at 5000 microM.
      The effects of the two treatments were additive and also differed from each other
      with substitution of gluconate for extracellular chloride. Thus, ascorbate
      release from endothelial cells can be potentiated by two distinct pathways -
      hypotonic shock mediated and ATP/Ca2+ stimulated.

PMID- 16962580
TI  - Prevention of selenite-induced cataractogenesis by acetyl-L-carnitine: an
      experimental study.
AB  - Several studies have suggested that antioxidants retard the process of
      cataractogenesis by scavenging free oxygen radicals. The present study sought to
      assess the efficacy of the antioxidant acetyl-L-carnitine (ALCAR) in preventing
      selenite-induced cataractogenesis in an experimental setting. The first, in vitro
      phase of the study was performed on lenses from Wistar rats incubated for 24 h at
      37 degrees C in Dulbecco's Modified Eagle Medium (DMEM) alone (control, Group I),
      or in DMEM containing 100 microM of selenite (Group II) or in DMEM containing 100
      microM of selenite and 200 microM/ml ALCAR added at the same time as selenite
      (Group IIIa) or 30 min, 1 h or 2 h later (Groups IIIb, IIIc and IIId,
      respectively). Gross morphological examination of these lenses revealed dense
      opacification (cataract formation) in Group II, minimal opacification in some
      Group IIIa lenses and no opacification in Group I. The mean activities of the
      antioxidant enzymes catalase and glutathione peroxidase were significantly lower
      in Group II than in Group I or Group IIIa lenses, while malondialdehyde
      concentration (an indicator of lipid peroxidation) was significantly higher in
      Group II lenses than that in Group I or Group IIIa lenses. The second, in vivo
      phase of the study revealed dense opacification (cataract formation) in 100% of
      Wistar rat pups receiving subcutaneous sodium selenite alone (19 microM/kg body
      weight) but in only 37.5% of those receiving subcutaneous selenite and
      intraperitoneal ALCAR. These data suggest that ALCAR is able to significantly
      retard experimental selenite-induced cataractogenesis.

PMID- 16962581
TI  - Macrophage colony stimulating factor is a crucial factor for the intrinsic
      macrophage response in mice heterozygously deficient for the myelin protein P0.
AB  - Mouse mutants heterozygously deficient for the myelin protein P0 (P0+/-) resemble
      certain forms of human hereditary neuropathies. Endoneurial macrophages of
      intrinsic origin are intimately involved in the pathogenesis of the demyelinating
      neuropathy in these mutants. We have previously shown that deficiency for
      macrophage colony stimulating factor (M-CSF) prevents an increase of the number
      of endoneurial macrophages and alleviates the mutants' demyelinating phenotype.
      The aim of this study was to investigate which population of endoneurial
      macrophages - long-term resident macrophages or recently infiltrated macrophages 
      is affected by M-CSF deficiency. For this purpose, we generated bone marrow
      chimeric mice by transplanting GFP+ bone marrow into P0 mutants (P0+/-) and P0
      mutants that lack M-CSF (P0+/- mcsf-op). This enabled us to discriminate recently
      infiltrated short-term resident GFP+ macrophages from long-term resident GFP-
      macrophages. Three months after bone marrow transplantation, P0+/- mice
      expressing M-CSF showed a substantial upregulation and activation of both GFP-
      and GFP+ macrophages in femoral nerves when compared to P0+/+ mice. In contrast,
      in P0+/- mcsf-op mutants, both GFP- and GFP+ macrophages did not substantially
      increase. Only small numbers of GFP+ but no GFP- macrophages were activated and
      phagocytosed myelin in chimeric P0+/- mcsf-op mutants, possibly reflecting recent
      activation outside the endoneurium before entering the nerve. Our findings
      demonstrate that M-CSF is crucial for the activation, in situ increase and myelin
      phagocytosis of both long-term and short-term resident endoneurial macrophages in
      P0+/- myelin mutants. M-CSF is, therefore, considered as a target candidate for
      therapeutic strategies to treat human demyelinating neuropathies.

PMID- 16962582
TI  - Point source concentration of GDNF may explain failure of phase II clinical
      trial.
AB  - Significant differences have been reported in results from three clinical trials
      evaluating intraputamenal infusion of glial cell line-derived neurotrophic factor
      (GDNF) for the treatment of Parkinson's disease. To determine if problems in drug
      bioavailability could have contributed to the discrepancies between studies, we
      have analyzed the distribution of intraputamenally infused GDNF in the rhesus
      monkey brain using the delivery system and infusion protocol followed in a phase
      2 clinical trial that failed to achieve its primary endpoint. I125-GDNF was
      unilaterally infused into the putamen of three adult rhesus monkeys for 7 days.
      Three age- and sex-matched animals received vehicle infusions following identical
      procedures. GDNF levels in the brain, peripheral organs, blood and CSF were
      quantified and mapped by GDNF immunocytochemistry, GDNF ELISAs and I125
      measurements. Infused GDNF was found to be unevenly concentrated around the
      catheter, with tissue levels dropping exponentially with increasing distance from
      the point source of the single opening in the catheter tip. The volume of
      distribution of GDNF around the catheter, as determined by immunocytochemistry,
      varied over four-fold between animals ranging from 87 to 369 mm3. The
      concentration of GDNF around the catheter tip and limited diffusion into
      surrounding brain parenchyma support the hypothesis that drug bioavailability was
      limited to a small portion (2-9%) of the human putamen in the clinical trial
      using this catheter and infusion protocol.

PMID- 16962584
TI  - Functional analysis of a calcium-binding transcription factor involved in plant
      salt stress signaling.
AB  - Calcium is known to serve as a secondary messenger to mediate salt stress
      signaling pathway. We found a calcium-binding basic/helix-loop-helix-type
      transcription factor (AtNIG1) as a salt stress-responsive gene by using the
      suppression subtractive hybridization. The AtNIG1 was targeted into nucleus and
      bound to (45)Ca(2+), suggesting that AtNIG1 is a nuclear calcium-binding protein.
      In addition, AtNIG1 bound specifically to the E-box-DNA sequence (CANNTG), which
      is found in the promoter regions of many salt stress-related genes. Functional
      analyses with an atnig1-1 knockout mutant revealed that the mutant plants show
      enhanced sensitivity to salt stress. Further analyses indicated that the atnig1-1
      plants have reduced survival rate, fresh weight, chlorophyll content, and protein
      content upon salt stress, suggesting that the AtNIG1 plays a critical role in
      plant salt stress signaling. Therefore, this study represents that AtNIG1 is the
      first known calcium-binding transcription factor involved in plant salt stress
      signaling.

PMID- 16962583
TI  - Schistosoma bovis: plasminogen binding in adults and the identification of
      plasminogen-binding proteins from the worm tegument.
AB  - Schistosoma bovis is a ruminant haematic parasite that lives for years in the
      mesenteric vessels of the host. The aim of this work was to investigate the
      ability of adult S. bovis worms to interact with plasminogen, a central component
      in the host fibrinolytic system. Confocal microscopy analysis revealed that
      plasminogen bound to the tegument surface of the male-but not female-S. bovis
      worms and that this binding was strongly dependent on lysine residues. It was
      also observed that a protein extract of the worm tegument (TG) had the capacity
      to generate plasmin and to enhance the plasmin generation by the tissue-type
      plasminogen activator. Proteomic analysis of the TG extract identified 10
      plasminogen-binding proteins, among which the major ones were enolase,
      glyceraldehyde-3-phosphate dehydrogenase and actin. This study represents the
      first report about the binding of plasminogen to Schistosoma sp. proteins.

PMID- 16962585
TI  - The budding yeast Pichia pastoris has a novel Sec23p homolog.
AB  - In Pichia pastoris, coat protein complex II (COPII) vesicles form at discrete
      transitional ER (tER) sites. Analyzing COPII coat proteins in this yeast will
      help to reveal the mechanisms of tER organization. Here, we show that like
      Saccharomyces cerevisiae, P. pastoris contains essential SEC23 and SEC24 genes,
      as well as the non-essential SEC24 homolog LST1. In addition, P. pastoris
      contains a novel non-essential SEC23 homolog that we have designated SHL23. The
      products of all four genes are concentrated at tER sites. Deletion of SHL23 does
      not disrupt tER morphology. As judged by two-hybrid analysis, Sec23p associates
      with both Sec24p and Lst1p, whereas Shl23p associates selectively with Lst1p.
      These results suggest that P. pastoris COPII vesicles contain an Shl23p/Lst1p
      complex that is absent in S. cerevisiae.

PMID- 16962586
TI  - E2F factors rate controls the dual role of CDE/E2F composite element: a model of
      E2F-regulated gene expression in plant development.
AB  - The promoters of several E2F-regulated genes identified in plants contain a
      variety of E2F motifs, notably a composite element consisting of a "CDE-like
      element" C/GGCGG on one strand, described as repressor in animals, associated
      with an E2F element on the complementary strand. This detailed study throughout
      plant development using ribonucleotide reductase promoters, allows us to propose
      a model, where E2F and composite elements play a dual role. Such regulation is
      mainly conditioned by the availability of E2F factors in tissues and during the
      cell cycle in tobacco.

PMID- 16962587
TI  - Methylated polyphenols are poor "chemical" antioxidants but can still effectively
      protect cells from hydrogen peroxide-induced cytotoxicity.
AB  - Several polyphenolic compounds, including flavonoids and phenolic acids, were
      compared with their per-methylated forms in both chemical and cell-based assays
      for antioxidant capacity. Methylation largely eliminated "chemical" antioxidant
      capacity, according to ferric reducing antioxidant power and oxygen radical
      absorbance capacity assays. Methylation, however, only moderately reduced
      protection of human Jurkat cells in culture, from hydrogen peroxide-mediated
      cytotoxicity, at physiologically relevant concentrations. Neither methylated nor
      un-methylated compounds were detectably metabolized by the cells. It appears that
      the protective mechanism of polyphenolic antioxidants against high concentrations
      of hydrogen peroxide in human cells may be largely unrelated to chemical
      antioxidant capacity.

PMID- 16962588
TI  - Identification and characterization of selenoprotein K: an antioxidant in
      cardiomyocytes.
AB  - Selenoprotein K (SelK) is a newly identified selenoprotein. We showed that
      selenium incorporation into SelK was dependent on the 3'UTR of SelK mRNA. Sec
      insertion sequence (SECIS) RNA binding assays demonstrated that human SBP2 bound
      to the SelK SECIS element through the conserved non-Watson-Crick base pair
      quartet but not the AAT motif. Examination of the expression pattern revealed
      that human SelK mRNA was highly expressed in heart. Immunofluorescence analysis
      showed that SelK localized to the endoplasmic reticulum. Using SelK recombinant
      adenovirus, we found that overexpression of SelK attenuated the intracellular
      reactive oxygen species level and protected cells from oxidative stress-induced
      toxicity in cardiomyocytes. Our findings indicated that SelK is a novel
      antioxidant in cardiomyocytes and is related to the regulation of cellular redox
      balance.

PMID- 16962589
TI  - The nucleotide exchange factor activity of Grp170 may explain the non-lethal
      phenotype of loss of Sil1 function in man and mouse.
AB  - Recent genetic work characterized homozygous mutations in the SIL1 gene as cause
      for the neurodegeneration that is associated with Marinesco-Sjogren syndrome in
      man and the woozy mouse mutant. All reported mutations were expected to result in
      loss of Sil1 function. Sil1 has previously been shown to act as nucleotide
      exchange factor for the molecular chaperone immunoglobulin heavy chain binding
      protein (BiP) in the lumen of the endoplasmic reticulum (ER). In the yeast ER
      Lhs1p was shown to be able to substitute for Sil1p and to represent an
      alternative nucleotide exchange activity. Therefore, by analogy the mammalian
      ortholog of Lhs1p, Grp170, was suggested to be able to compensate for the loss of
      Sil1 function in many mammalian organs. Here we characterize mammalian Grp170 as
      alternative nucleotide exchange factor for BiP, thus providing a likely
      explanation for the non-lethal phenotype of the homozygous human and murine SIL1
      mutations.

PMID- 16962590
TI  - Peridinin-chlorophyll-protein reconstituted with chlorophyll mixtures:
      preparation, bulk and single molecule spectroscopy.
AB  - Reconstitution of the 16 kDa N-terminal domain of the peridinin-chlorophyll
      protein, N-PCP, with mixtures of chlorophyll a (Chl a) and Chl b, resulted in 32
      kDa complexes containing two pigment clusters, each bound to one N-PCP. Besides
      homo-chlorophyllous complexes, hetero-chlorophyllous ones were obtained that
      contain Chl a in one pigment cluster, and Chl b in the other. Binding of Chl b is
      stronger than that of the native pigment, Chl a. Energy transfer from Chl b to
      Chl a is efficient, but there are only weak interactions between the two
      pigments. Individual homo- and hetero-chlorophyllous complexes were investigated
      by single molecule spectroscopy using excitation into the peridinin absorption
      band and scanning of the Chl fluorescence, the latter show frequently well
      resolved emissions of the two pigments.

PMID- 16962591
TI  - About lipids and toxins.
AB  - Many mono or multicellular organisms secrete soluble proteins, referred to as
      protein toxins, which alter the behavior of foreign, or target cells, possibly
      leading to their death. These toxins affect either the cell membrane by forming
      pores or modifying lipids, or some intracellular target. To reach this target,
      they must cross one of the cellular membranes, generally that of an intracellular
      organelle. As described in this minireview, lipids play crucial roles in the
      intoxication process of most if not all toxins, by allowing/promoting binding,
      endocytosis, trafficking and/or translocation into the cytoplasm.

PMID- 16962593
TI  - Rab14 is part of the early endosomal clathrin-coated TGN microdomain.
AB  - Rab14 localizes to the Golgi/TGN and to early endosomes, but its biological
      function remains unclear. By structural modeling, we identified Rab14-specific
      residues and established a close relationship between the Rab2/Rab4/Rab14,
      Rab11/25 and Rab39 sub-groups within the Rab protein family. By quantitative
      confocal microscopy and by density centrifugation we show that Rab14 is part of
      the early endosomal AP-1 microdomain. Overexpression of a dominant-negative Rab14
      GTP-binding mutant that solely localizes to the Golgi donor compartment
      accelerated EGF degradation. We suggest that the AP-1 microdomain represents the
      interconnecting compartment in which Rab14 vesicles cycle between early endosomes
      and the Golgi cisternae.

PMID- 16962592
TI  - Honokiol causes the p21WAF1-mediated G(1)-phase arrest of the cell cycle through
      inducing p38 mitogen activated protein kinase in vascular smooth muscle cells.
AB  - Honokiol, an active component in extracts of Magnolia officinalis, has been
      proposed to play a role in anti-inflammatory, antioxidant activity, anti
      angiogenic and anti-tumor activity. Although honokiol has a variety of
      pharmacological effects on certain cell types, its effects on vascular smooth
      muscle cells (VSMC) are unclear. This issue was investigated in the present
      study, honokiol was found to inhibit cell viability and DNA synthesis in cultured
      VSMC. These inhibitory effects were associated with G1 cell cycle arrest.
      Treatment with honokiol blocks the cell cycle in the G1 phase, down-regulates the
      expression of cyclins and CDKs and up-regulates the expression of p21WAF1, a CDK
      inhibitor. While honokiol did not up-regulate p27, it caused an increase in the
      promoter activity of the p21WAF1 gene. Immunoblot and deletion analysis of the
      p21WAF1 promoter showed that honokiol induced the expression of p21WAF1 and that
      this expression was independent of the p53 pathway. Furthermore, the honokiol
      mediated signaling pathway involved in VSMC growth inhibition was examined. Among
      the relevant pathways, honokiol induced a marked activation of p38 MAP kinase and
      JNK. The expression of dominant negative p38 MAP kinase and SB203580, a p38 MAP
      kinase specific inhibitor, blocked the expression of honokiol-dependent p38 MAP
      kinase and p21WAF1. Consistently, blockade of p38 MAPK kinase function reversed
      honokiol-induced VSMC proliferation and cell cycle proteins. These data
      demonstrate that the p38 MAP kinase pathway participates in p21WAF1 induction,
      subsequently leading to a decrease in the levels of cyclin D1/CDK4 and cyclin
      E/CDK2 complexes and honokiol-dependent VSMC growth inhibition. In conclusion,
      these findings concerning the molecular mechanisms of honokiol in VSMC provides a
      theoretical basis for clinical approaches to the use therapeutic agents in
      treating atherosclerosis.

PMID- 16962594
TI  - Molecular determinants of dihydrouridine synthase activity.
AB  - Dihydrouridine is one of the most abundant modified bases in tRNA. However,
      little is known concerning the biochemistry of dihydrouridine synthase (DUS)
      enzymes. To identify molecular determinants that are necessary for DUS activity,
      we have developed a DUS-complementation assay in Escherichia coli. Using this
      assay, we have identified amino-acid residues that are critical for the activity
      of YjbN, an E. coli DUS. We also show that the aq1598 gene product, a putative
      DUS from Aquifex aeolicus, catalyzes dihydrouridine formation, providing the
      first biochemical demonstration that A. aeolicus encodes an active DUS.

PMID- 16962595
TI  - UCP3 in muscle wasting, a role in modulating lipotoxicity?
AB  - UCP3 has been postulated to function in the defense against lipid-induced
      oxidative muscle damage (lipotoxicity). We explored this hypothesis during
      cachexia in rats (zymosan-induced sepsis), a condition characterized by increased
      oxidative stress and supply of fatty acids to the muscle. Muscle UCP3 protein
      content was increased 2, 6 and 11 days after zymosan injection. Plasma FFA levels
      were increased at day 2, but dropped below control levels on days 6 and 11.
      Muscular levels of the lipid peroxidation byproduct 4-hydroxy-2-nonenal (4-HNE)
      were increased at days 6 and 11 in zymosan-treated rats, supporting a role for
      UCP3 in modulating lipotoxicity during cachexia.

PMID- 16962596
TI  - Cloning of three estrogen receptors (ER) from killifish (Fundulus heteroclitus):
      differences in populations from polluted and reference environments.
AB  - Epidemiological, wildlife, and laboratory studies support the hypothesis that
      chemicals released into the environment through anthropogenic activities are
      responsible for abnormalities of reproduction and development. Although the New
      Bedford Harbor (NBH) killifish population has survived and reproduced
      successfully for >50 yr ( approximately 20 generations), fish have high body
      burdens of the major NBH contaminants (polychlorinated biphenyls); elevated
      levels of P450 aromatase B and vitellogenin mRNA (markers of estrogen effect);
      and evidence of endocrine disruption. To investigate possible adaptive changes in
      the estrogen response system of NBH killifish, we cloned the estrogen receptors
      (ER) from killifish populations resident in NBH and a relatively unpolluted
      reference site (Scorton Creek MA, SC). ERalpha, -betaa, and -betab cDNAs encoding
      full-length polypeptides of 620, 543, and 672 amino acids, respectively, were
      identified. Each ER subtype had multiple splice variants, single nucleotide
      polymorphisms (SNPs), and a characteristic tissue distribution and developmental
      profile. As measured by real-time quantitative RT-PCR analysis, the overall
      tissue distribution of each ER was similar in NBH and SC fish, implying that the
      regulatory pathways which maintain tissue-specific expression are largely
      unchanged by long term pollutant exposure. Nonetheless, a striking difference was
      seen in the quantity of mRNA of the estrogen-inducible gene ERalpha, which was
      significantly lower in brain, liver and ovaries of reproductively active NBH as
      compared to SC females. Paradoxically, despite the "estrogenic" NBH environment,
      ERalpha mRNA levels did not differ in reproductively inactive NBH and SC females,
      or in males at the two sites at any time of year. We interpret results in NBH
      fish as due in part to a deficit of circulating estrogen, and in part to
      pollutant-mediated hyporesponsiveness of the ERalpha gene. In marked contrast to
      adult fish, ERalpha was elevated approximately 5-fold in NBH as compared to SC
      embryos/larvae, perhaps indicative of estrogenic chemicals in yolk. We conclude
      that contaminants in the NBH environment impact molecular components of the
      estrogen signaling pathways in resident killifish populations. Whether these
      changes are transient or heritable requires further study.

PMID- 16962597
TI  - Temporal profile of brain and pituitary GnRHs, GnRH-R and gonadotropin mRNA
      expression and content during early development in European sea bass
      (Dicentrarchus labrax L.).
AB  - A likely endocrine control mechanism for sexual differentiation in size-graded
      populations of European sea bass (Dicentrarchus labrax) is proposed by evaluating
      the brain expression and pituitary content of two forms of gonadotropin-releasing
      hormone (GnRH), namely sea bream (sbGnRH) and salmon (sGnRH), the pituitary
      expression of one subtype of GnRH receptor (dlGnRH-R-2A) and the three
      gonadotropin (GtH) subunits, namely glycoprotein alpha (GPalpha), follicle
      stimulating hormone beta (FSHbeta) and luteinizing hormone beta (LHbeta), as well
      as the pituitary and plasma LH levels between 50 and 300 days post-hatching
      (dph). Four gradings were conducted between 2 and 8 months after hatching,
      resulting in a population of large and small individuals, having 96.5% females
      (female-dominant population) and 69.2% males (male-dominant population),
      respectively, after the last grading. The onset of gonadal differentiation was
      different in the two sexes, and coincided with a peak of expression of sbGnRH or
      sGnRH. Furthermore, the expression of these GnRHs was correlated with the
      expression of dlGnRH-R-2A. Sex-related differences in the brain and pituitary
      content of sbGnRH were also found at the time of sexual differentiation.
      Moreover, the observed sexual dimorphism at the transcriptional or synthesis
      level of these GnRH forms suggests that a different neuro-hormonal regulation is
      operating according to sex. At the onset of sex differentiation, FSHbeta
      transcriptional activity reached maximal values, which were maintained until the
      completion of the process. The present study suggests a role for sbGnRH, sGnRH
      and the dlGnRH-R-2A during gonadal differentiation, possibly through enhancement
      of FSHbeta gene expression. In males, a different endocrine regulation seems to
      exist also during spermiogenesis and spermiation, when gene transcription,
      peptide synthesis and release of LH are of greater importance.

PMID- 16962598
TI  - The impact of hs C-reactive protein and other inflammatory biomarkers on long
      term cardiovascular mortality in patients with acute coronary syndromes.
AB  - We evaluated whether high circulating levels of serum amyloid A (SAA),
      fibrinogen, interleukin-6 (IL-6) or leukocytes count (LC), can provide any
      additional predictive value over that provided by hs C-reactive protein (hs-CRP)
      for the incidence of 5-year cardiovascular mortality, in 458 and 476 consecutive
      patients with ST-segment elevation myocardial infarction (STEMI) and non-ST
      segment elevation acute coronary syndromes (NSTE-ACS), respectively. By 5 years
      the incidence of cardiovascular mortality was 37.3% and 35.5% in patients with
      STEMI and NSTE-ACS, respectively. Each of the study inflammatory biomarkers
      conferred independent to clinical risk predictors (and to cardiac troponin I)
      long-term prognostic information (all p<0.05), but only LC provided additional
      predictive value over that provided by hs-CRP, in either cohort (p<0.05). By
      multivariate Cox regression analysis, hs-CRP (p<0.001 for both cohorts) and LC
      (p=0.009 and p<0.001 for STEMI and NSTE-ACS, respectively) were the only
      inflammatory biomarkers independently associated with the incidence of 5-year
      cardiovascular mortality. According to the present results high circulating
      levels of LC but not of SAA, fibrinogen or IL-6 can provide additional long-term
      predictive value over that provided by hs-CRP in patients with acute coronary
      syndromes.

PMID- 16962599
TI  - Measurement and modelling of x-direction apparent mass of the seated human body
      cushioned seat system.
AB  - For modelling purposes and for evaluation of driver's seat performance in the
      vertical direction various mechano-mathematical models of the seated human body
      have been developed and standardized by the ISO. No such models exist hitherto
      for human body sitting in an upright position in a cushioned seat upper part,
      used in industrial environment, where the fore-and-aft vibrations play an
      important role. The interaction with the steering wheel has to be taken into
      consideration, as well as, the position of the human body upper torso with
      respect to the cushioned seat back as observed in real driving conditions. This
      complex problem has to be simplified first to arrive at manageable simpler
      models, which still reflect the main problem features. In a laboratory study
      accelerations and forces in x-direction were measured at the seat base during
      whole-body vibration in the fore-and-aft direction (random signal in the
      frequency range between 0.3 and 30 Hz, vibration magnitudes 0.28, 0.96, and 2.03
      ms(-2) unweighted rms). Thirteen male subjects with body masses between 62.2 and
      103.6 kg were chosen for the tests. They sat on a cushioned driver seat with
      hands on a support and backrest contact in the lumbar region only. Based on these
      laboratory measurements a linear model of the system-seated human body and
      cushioned seat in the fore-and-aft direction has been developed. The model
      accounts for the reaction from the steering wheel. Model parameters have been
      identified for each subject-measured apparent mass values (modulus and phase).
      The developed model structure and the averaged parameters can be used for further
      bio-dynamical research in this field.

PMID- 16962600
TI  - Analysis of pesticides and metabolites in Spanish surface waters by isotope
      dilution gas chromatography/mass spectrometry with previous automated solid-phase
      extraction Estimation of the uncertainty of the analytical results.
AB  - A method based on isotope dilution gas chromatography/mass spectrometry (GC/MS)
      with automated solid-phase extraction (SPE) is described for the analysis of 32
      pesticides and metabolites in surface waters. This approach consist in the use of
      nine isotopically labelled representative pesticides as internal standards, which
      allows high accuracy (trueness and precision) and sensitivity for most analysed
      compounds, as it is required for isotope dilution-based methods. Uncertainties
      associated with pesticide determination in real samples were estimated using
      quality assurance/quality control (QA/QC) data. For most pesticides expanded
      uncertainty was below 40%, according to the commonly established requirements for
      analytical results. Ninety three Spanish surface waters collected in June-July
      and September-November 2004 were analysed. Concentration and occurrence of
      pesticides were evaluated. These parameters were higher in the summer than in the
      autumn period. In summer four pesticides were found in more than 50% of the
      analysed samples and four compounds were detected above the concentration level
      of 1 microg/l (atrazine, terbutylazine, 3,4-dichloroaniline and fenitrothion),
      while in autumn percentage of detection was below 50% for all pesticides and only
      one compound (terbutylazine) exceeded 1 microg/l.

PMID- 16962601
TI  - Identification and quantification of the constituents of madder root by gas
      chromatography and high-performance liquid chromatography.
AB  - The possibilities in the identification and quantitation of the constituents of
      Rubia tinctorum L.'s root, called also madder root, was described and compared by
      gas chromatography (GC)-MS, high-performance liquid chromatography (HPLC)
      UV/photodiode array detection (DAD) and HPLC-MS: chromatographic analyses were
      carried out in parallel, from the same samples/extracts/hydrolyzates.
      Anthraquinone glycosides, anthraquinones, carboxylic acids and sugars were
      determined directly in the presence of the matrix and in its extracts without and
      subsequently to hydrolyses. Hydrolyses were performed as a function of time, with
      hydrochloric and trifluoroacetic acids, as well as enzymatically. Data revealed
      that as hydrolyzing agent trifluoroacetic acid is to be preferred. Madder root's
      anthraquinones (pseudopurpurin/purpurin, alizarin, lucidin, munjistin,
      nordamnacanthal) were identified on the basis of their absorption spectra (HPLC
      DAD) and fragmentation patterns by GC-MS and HPLC-MS, equally. Reproducibility of
      anthraquinone's quantitation, by HPLC-DAD and GC-MS, in the concentration ranges
      of 4 x 10(-5) to 3 x 10(-2)g/g dried sample, provided an average reproducibility
      of 4.2% (varying between 0.9 and 9.4% relative standard deviation (RSD
      percentages)). Carboxylic acids (malic, citric, quinic, rosmarinic acids) and
      saccharides (xylose, ribose, fructose, glucose, sucrose, primverose) were
      quantified as their trimethylsilyl (oxime) ether/ester derivatives by GC-MS, in
      the concentration ranges of 10(-5)g to 10(-2)g/g dried sample, with an average
      reproducibility of 4.7% RSD.

PMID- 16962602
TI  - On-line capillary based quantitative analysis of a heterocyclic amine in human
      urine.
AB  - A high through-put miniaturised separation-quantification method for the
      heterocyclic aromatic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      (PhIP) in urine was developed. The limit of detection was of 0.65 fmol (0.14 pg)
      injected or 65 pM. Heterocyclic aromatic amines are mutagenic and carcinogenic
      compounds formed at low levels in protein-rich food during cooking. Due to the
      low concentrations and the high complexity of the matrix in which they exist
      (food, blood, and urine), and the often small sample volumes (capillary blood;
      urine, blood and milk from small animals), very sensitive and selective
      analytical methods are required for their detection. Miniaturization was
      accomplished by micro solid-phase extraction in capillaries with blue chitin as
      solid-phase, coupled on-line (in-capillary) to capillary electrophoresis with
      nanospray tandem mass spectrometric detection. This new technique provided a
      total analysis time of only 15 min, including extraction and separation, together
      with low sample and solvent consumption. Blue chitin showed high tolerance
      towards the urine matrix. Urine collected 12h after consumption of fried chicken
      contained 1.8 nmol L(-1) (0.40 pg microL(-1)) of PhIP.

PMID- 16962603
TI  - Fabrication, characterization, and formation mechanism of hollow spindle-like
      hematite via a solvothermal process.
AB  - As a novel hollow nanostructure, hollow spindle-like hematite with uniform size
      and morphology was solvothermally synthesized. These hollow polycrystalline
      particles with the length of 220-300 nm, the width of 70-100 nm, and the wall
      thickness of ca. 18 nm were characterized by TEM, FE-SEM, XRD, FT-IR, TGA,
      Mossbauer spectrum, and XPS methods. It was found that these hollow-structured
      particles were transformed from their original solid spindle particles. During
      the hollow structure formation process, the interiors of solid particles were
      preferentially dissolved while the retained exteriors were protected by
      coordinated sulfate ions. The formation mechanism was proposed as a coordination
      assisted dissolution process occurred in a reverse microemulsion system.

PMID- 16962604
TI  - Surface complexation mechanism and modeling in Cr(III) biosorption by a
      microalgal isolate, Chlorella miniata.
AB  - The mechanism involved in the removal of Cr(III) by a green microalgal isolate,
      Chlorella miniata, was examined based on a series of batch experiments and
      microscopic analyses, and a mathematical model was proposed. Results showed that
      Cr(III) biosorption increased with the increase of pH from 2.0 to 4.5, and no
      significant changes in biosorption outside this pH range. Langmuir isotherm
      indicated that the maximum Cr(III) sorption capacity of Chlorella miniata was
      14.17, 28.72, and 41.12 mg g(-1) biomass at pH 3.0, 4.0, and 4.5, respectively.
      Results from desorption studies, SEM (scanning electron microscopy), TEM
      (transmission electron microscopy), and EDX (energy-dispersive X-ray
      spectroscope) analyses confirmed that surface complexation was the main process
      involved in Cr(III) biosorption. Potentiometric titration revealed that carboxyl
      (pKa1 = 4.10), phosphonate (pKa2 = 6.36) and amine (pKa3 = 8.47) functional
      groups on the surface of Chlorella miniata were the possible sites for Cr uptake,
      and their average amounts were 0.53, 0.39, and 0.36 mmol g(-1) biomass,
      respectively. A surface complexation model further indicated that carboxyl group
      played the main role in Cr(III) complexation, with a binding constant of K11 =
      1.87 x 10(-4) and K12 = 6.11 x 10(-4) for Cr3+ and Cr(OH)2+, respectively. This
      model also suggested that the hydroxy species was more easily to complex with the
      cell surface of Chlorella miniata.

PMID- 16962606
TI  - Photopatterning in poly-L-lysine thin films using UV-enhanced hydrophilicity.
AB  - Deep UV lithography on poly-L-lysine thin films was used to generate microarrays
      with enhanced hydrophilicity. This was manifested as adsorption of ambient
      humidity from air by areas exposed to UV fluence around 5 J/cm2 and was made
      visible by phase-contrast microscopy. Kinetics of adsorption was investigated by
      a novel technique involving fabrication of submicrometer hydrophilicity grating
      by two-beam UV interferometry. In an aqueous colloidal medium, gold and
      polystyrene microspheres preferentially attach to areas that are relatively less
      hydrophilic, i.e., those areas not exposed to UV light. This observation provides
      a method for fabricating micro- and nanoporous arrays with controlled porosity.
      The technique is demonstrated with microspheres of sizes between 250 nm and 10
      microm.

PMID- 16962605
TI  - Metallomicellar catalysis: hydrolysis of phosphate monoester and phosphodiester
      by Cu(II), Zn(II) complexes of pyridyl ligands in CTAB micellar solution.
AB  - The catalytic hydrolysis of bis(p-nitrophenyl) phosphate (BNPP) and p-nitrophenyl
      phosphate (NPP) by metallomicelles composed of Cu(II) or Zn(II) complexes of
      bispyridine-containing alkanol ligands in CTAB micellar solution was investigated
      at 30 degrees C. The experimental results indicate that the complexes with a 1:1
      ratio of ligands to metal ions for ligands 1 (1,7-bis(6-hydroxymethyl-2-pyridyl)
      2,6-dioxaheptane) and 3 (1,4-bis[(6-hydroxymethyl-2-pyridyl)-2-oxapropyl]benzene)
      and a 1:2 ratio of ligands to metal ions for ligand 2 (1,14-bis(6-hydroxymethyl-2
      pyridyl)-2,13-dioxatetradecane) in CATB micellar solution are the active species
      for the catalytic hydrolysis of BNPP and NPP, respectively. The ternary complex
      kinetic model for metallomicellar catalysis was employed to obtain the relative
      kinetic and thermodynamic parameters, which demonstrated the catalytic mechanism
      for the hydrolysis of BNPP and NPP by metallomicelles.

PMID- 16962607
TI  - A concentration polarization model for the ultrafiltration of nonionic
      surfactants.
AB  - A theoretical model has been developed that describes ultrafiltration of nonionic
      surfactants. The model takes into account the fact that surfactants start to
      aggregate and form micelles at the critical micelle concentration. The model can
      be used to predict the performance of the membrane if the transport properties
      inside and at the membrane surface as well as the surfactant association
      behavior, are known. Three hydrophilic ultrafiltration membranes, made of
      regenerated cellulose, were used in the investigation. The cut-offs of the
      membranes were 10,000, 20,000, and 30,000 Da. The surfactant used in the
      investigation was the nonionic surfactant Triton X-100. The influence of the
      concentration of surfactant, transmembrane pressure and pure water flux were
      studied theoretically and experimentally. From the results presented in this work
      it can be concluded that the calculated values are in good agreement with
      experimental data.

PMID- 16962608
TI  - Dimerisation strategies for shark IgNAR single domain antibody fragments.
AB  - Immunoglobulin new antigen receptors (IgNARs) are unique single domain antibodies
      found in the serum of sharks. The individual variable (VNAR) domains bind antigen
      independently and are candidates for the smallest antibody-based immune
      recognition units (approximately 13 kDa). Here, we first isolated and sequenced
      the cDNA of a mature IgNAR antibody from the spotted wobbegong shark (Orectolobus
      maculatus) and confirmed the independent nature of the VNAR domains by dynamic
      light scattering. Second, we asked which of the reported antibody fragment
      dimerisation strategies could be applied to VNAR domains to produce small
      bivalent proteins with high functional affinity (avidity). In contrast to single
      chain Fv (scFv) fragments, separate IgNARs could not be linked into a tandem
      single chain format, with the resulting proteins exhibited only monovalent
      binding due solely to interaction of the N-terminal domain with antigen.
      Similarly, incorporation of C-terminal helix-turn-helix (dhlx) motifs, while
      resulting in efficiently dimerised protein, resulted in only a modest enhancement
      of affinity, probably due to an insufficiently long hinge region linking the
      antibody to the dhlx motif. Finally, generation of mutants containing half
      cystine residues at the VNAR C-terminus produced dimeric recombinant proteins
      exhibiting high functional affinity for the target antigens, but at the cost of
      50-fold decreased protein expression levels. This study demonstrates the
      potential for construction of bivalent or bispecific IgNAR-based binding reagents
      of relatively small size (approximately 26 kDa), equivalent to a monovalent
      antibody Fv fragment, for formulation into future diagnostic and therapeutic
      formats.

PMID- 16962609
TI  - Delineation of protein structure classes from multivariate analysis of protein
      Raman optical activity data.
AB  - Vibrational Raman optical activity (ROA), measured as a small difference in the
      intensity of Raman scattering from chiral molecules in right and left-circularly
      polarized incident light, or as the intensity of a small circularly polarized
      component in the scattered light, is a powerful probe of the aqueous solution
      structure of proteins. On account of the large number of structure-sensitive
      bands in protein ROA spectra, multivariate analysis techniques such as non-linear
      mapping (NLM) are especially favourable for determining structural relationships
      between different proteins. Here NLM is used to map a dataset of 80 polypeptide,
      protein and virus ROA spectra, considered as points in a multidimensional space
      with axes representing the digitized wavenumbers, into readily visualizable two
      and three-dimensional spaces in which points close to or distant from each other,
      respectively, represent similar or dissimilar structures. Discrete clusters are
      observed which correspond to the seven structure classes all alpha, mainly alpha,
      alphabeta, mainly beta, all beta, mainly disordered/irregular and all
      disordered/irregular. The average standardised ROA spectra of the proteins
      falling within each structure class have distinct features characteristic of each
      class. A distinct cluster containing the wheat protein A-gliadin and the plant
      viruses potato virus X, narcissus mosaic virus, papaya mosaic virus and tobacco
      rattle virus, all of which appear in the mainly alpha cluster in the two
      dimensional representation, becomes clearly separated in the direction of
      increasing disorder in the three-dimensional representation. This suggests that
      the corresponding five proteins, none of which to date has yielded high
      resolution X-ray structures, consist mainly of alpha-helix and disordered
      structure with little or no beta-sheet. This combination of structural elements
      may have functional significance, such as facilitating disorder-to-order
      transitions (and vice versa) and suppressing aggregation, in these proteins and
      also in sequences within other proteins. The use of ROA to identify proteins
      containing significant amounts of disordered structure will, inter alia, be
      valuable in structural genomics/proteomics since disordered regions often inhibit
      crystallization.

PMID- 16962610
TI  - Directed evolution of an anti-prion protein scFv fragment to an affinity of 1 pM
      and its structural interpretation.
AB  - Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative prion disease
      affecting cattle that is transmissible to humans, manifesting as a variant of
      Creutzfeldt-Jakob disease (vCJD) likely following the consumption of meat
      contaminated with BSE prions. High-affinity antibodies are a prerequisite for the
      development of simple, highly sensitive and non-invasive diagnostic tests that
      are able to detect even small amounts of the disease-associated PrP conformer
      (PrP(Sc)). We describe here the affinity maturation of a single-chain Fv antibody
      fragment with a binding affinity of 1 pM to a peptide derived from the
      unstructured region of bovine PrP (BoPrP (90-105)). This is the tightest peptide
      binding antibody reported to date and may find useful application in diagnostics,
      especially when PrP(Sc) is pretreated by denaturation and/or proteolysis for
      peptide-like presentation. Several rounds of directed evolution and off-rate
      selection with ribosome display were performed using an antibody library
      generated from a single PrP binder with error-prone PCR and DNA-shuffling. As the
      correct determinations of affinities in this range are not straightforward,
      competition biosensor techniques and KinExA methods were both applied and
      compared. Structural interpretation of the affinity improvement was performed
      based on the crystal structure of the original prion binder in complex with the
      BoPrP (95-104) peptide by modeling the corresponding mutations.

PMID- 16962611
TI  - Functional and structural role of amino acid residues in the even-numbered
      transmembrane alpha-helices of the bovine mitochondrial oxoglutarate carrier.
AB  - The mitochondrial oxoglutarate carrier exchanges cytosolic malate for 2
      oxoglutarate from the mitochondrial matrix. Orthologs of the carrier have a high
      degree of amino acid sequence conservation, meaning that it is impossible to
      identify residues important for function on the basis of this criterion alone.
      Therefore, each amino acid residue in the transmembrane alpha-helices H2 and H6
      was replaced by a cysteine in a functional mitochondrial oxoglutarate carrier
      that was otherwise devoid of cysteine residues. The effects of the cysteine
      replacement and subsequent modification by sulfhydryl reagents on the initial
      uptake rate of 2-oxoglutarate were determined. The results were evaluated using a
      structural model of the oxoglutarate carrier. Residues involved in inter-helical
      and lipid bilayer interactions tolerate cysteine replacements or their
      modifications with little effect on transport activity. In contrast, the majority
      of cysteine substitutions in the aqueous cavity had a severe effect on transport
      activity. Residues important for function of the carrier cluster in three regions
      of the transporter. The first consists of residues in the [YWLF]- [KR]-G-X-X-P
      sequence motif, which is highly conserved in all members of the mitochondrial
      carrier family. The residues may fulfill a structural role as a helix breaker or
      a dynamic role as a hinge region for conformational changes during translocation.
      The second cluster of important residues can be found at the carboxy-terminal end
      of the even-numbered transmembrane alpha-helices at the cytoplasmic side of the
      carrier. Residues in H6 at the interface with H1 are the most sensitive to
      mutation and modification, and may be essential for folding of the carrier during
      biogenesis. The third cluster is at the midpoint of the membrane and consists of
      residues that are proposed to be involved in substrate binding.

PMID- 16962612
TI  - The crystal structure of mouse Nup35 reveals atypical RNP motifs and novel
      homodimerization of the RRM domain.
AB  - The nuclear pore complex mediates the transport of macromolecules across the
      nuclear envelope (NE). The vertebrate nuclear pore protein Nup35, the ortholog of
      Saccharomyces cerevisiae Nup53p, is suggested to interact with the NE membrane
      and to be required for nuclear morphology. The highly conserved region between
      vertebrate Nup35 and yeast Nup53p is predicted to contain an RNA-recognition
      motif (RRM) domain. Due to its low level of sequence homology with other RRM
      domains, the RNP1 and RNP2 motifs have not been identified in its primary
      structure. In the present study, we solved the crystal structure of the RRM
      domain of mouse Nup35 at 2.7 A resolution. The Nup35 RRM domain monomer adopts
      the characteristic betaalphabetabetaalphabeta topology, as in other reported RRM
      domains. The structure allowed us to locate the atypical RNP1 and RNP2 motifs.
      Among the RNP motif residues, those on the beta-sheet surface are different from
      those of the canonical RRM domains, while those buried in the hydrophobic core
      are highly conserved. The RRM domain forms a homodimer in the crystal, in
      accordance with analytical ultracentrifugation experiments. The beta-sheet
      surface of the RRM domain, with its atypical RNP motifs, contributes to
      homodimerization mainly by hydrophobic interactions: the side-chain of Met236 in
      the beta4 strand of one Nup35 molecule is sandwiched by the aromatic side-chains
      of Phe178 in the beta1 strand and Trp209 in the beta3 strand of the other Nup35
      molecule in the dimer. This structure reveals a new homodimerization mode of the
      RRM domain.

PMID- 16962613
TI  - Mood improvement after deep brain stimulation of the internal globus pallidus for
      tardive dyskinesia in a patient suffering from major depression.
AB  - Deep brain stimulation (DBS) has the unique characteristic to very precisely
      target brain structures being part of functional brain circuits in order to
      reversibly modulate their function. It is an established adjunctive treatment of
      advanced Parkinson's disease and has virtually replaced ablative techniques in
      this indication. Several cases have been published relating effectiveness in
      neuroleptics-induced tardive dyskinesia. It is also investigated as a potential
      treatment of mood disorders. We report on the case of a 62 years old female
      suffering from a treatment refractory major depressive episode with comorbid
      neuroleptic-induced tardive dyskinesia. She was implanted a deep brain
      stimulation treatment system bilaterally in the globus pallidus internus and
      stimulated for 18 months. As well the dyskinesia as also the symptoms of
      depression improved substantially as measured by the Hamilton Rating Scale of
      Depression (HRSD) score and the Burke-Fahn-Marsden-Dystonia-Rating-Scale (BFMDRS)
      score. Scores dropped for HRSD from 26 at baseline preoperatively to 13 after 18
      months; and for BFMDRS from 27 to 17.5. This case illustrates the potential of
      deep brain stimulation as a technique to be investigated in the treatment of
      severe and disabling psychiatric and movement disorders. DBS at different
      intracerebral targets being actually investigated for major depression might have
      similar antidepressant properties because they interact with the same cortico
      basal ganglia-thalamocortical network found to be dysfunctional in major
      depression.

PMID- 16962615
TI  - Spatially discrete metapopulation models with directional dispersal.
AB  - We use an age-structured discrete-time metapopulation model linking two sub
      populations through larval transport and directed movements of adults to study
      the implications of linkages among subpopulations for the stability and
      resilience of exploited species. Our two-habitat model, a generalization of
      Fogarty's inshore-offshore lobster population model, includes isolated habitats
      under compensatory (monotone) or overcompensatory (oscillatory) dynamics [M.J.
      Fogarty, Implications of migration and larval interchange in American lobster
      (Homarus americanus) stocks: spatial structure and resilience, in: G.S. Jamieson,
      A. Campbell (Eds.), Proc. of North Pacific Symposium on Invertebrate Stock
      Assessment and Management, Can. Spec. Publ. Fish. Aquat. Sci. 125 (1998) 273].
      Pre-migration local dynamics are selected from general classes of functions that
      capture the effects of competition for resources via contest (compensatory) and
      scramble (overcompensatory) intraspecific competitions. We explore the
      implications of these mechanisms on the long-term survival of exploited species.
      In particular, we use threshold parameters R(d)1 for Habitat 1 and R(d)2 for
      Habitat 2 together with precise mathematical definitions to prove that species
      persistence is possible at high levels of fishing in one habitat and low to
      moderate levels of fishing in the other. Our results support Fogarty's conclusion
      that conservative management of larval source populations could contribute to the
      resilience of exploited species.

PMID- 16962616
TI  - Discontinuous Galerkin method for piecewise regular solutions to the nonlinear
      age-structured population model.
AB  - A discontinuous Galerkin approximation of the nonlinear Lotka-McKendrick equation
      is considered in the frequent case when the solution is only piecewise regular.
      An O(h(r+1/2)) error estimate for rth order polynomial finite elements is proved,
      as well as piecewise H(1)-regularity of the exact solution which guarantees the
      error estimate for r=0. Certain implementational details which improve the
      robustness of the method are also addressed.

PMID- 16962614
TI  - Inhibition of soluble epoxide hydrolase reduces LPS-induced thermal hyperalgesia
      and mechanical allodynia in a rat model of inflammatory pain.
AB  - Soluble epoxide hydrolases catalyze the hydrolysis of epoxides in acyclic
      systems. In man this enzyme is the product of a single copy gene (EPXH-2) present
      on chromosome 8. The human sEH is of interest due to emerging roles of its
      endogenous substrates, epoxygenated fatty acids, in inflammation and
      hypertension. One of the consequences of inhibiting sEH in rodent inflammation
      models is a profound decrease in the production of pro-inflammatory and
      proalgesic lipid metabolites including prostaglandins. This prompted us to
      hypothesize that sEH inhibitors may have antinociceptive properties. Here we
      tested if sEH inhibitors can reduce inflammatory pain. Hyperalgesia was induced
      by intraplantar LPS injection and sEH inhibitors were delivered topically. We
      found that two structurally dissimilar but equally potent sEH inhibitors can be
      delivered through the transdermal route and that sEH inhibitors effectively
      attenuate thermal hyperalgesia and mechanical allodynia in rats treated with LPS.
      In addition we show that epoxydized arachidonic acid metabolites, EETs, are also
      effective in attenuating thermal hyperalgesia in this model. In parallel with the
      observed biological activity metabolic analysis of oxylipids showed that
      inhibition of sEH resulted with a decrease in PGD2 levels and sEH generated
      degradation products of linoleic and arachidonic acid metabolites with a
      concomitant increase in epoxides of linoleic acid. These data show that
      inhibition of sEH may become a viable therapeutic strategy to attain analgesia.

PMID- 16962617
TI  - Long range dispersal and spatial pattern formation in biological invasions.
AB  - In this paper we explore the consequences of long distance dispersal in
      biological invasion processes through simulations using a recently developed
      cellular automaton model. We show that long distance dispersal generate
      characteristic spatial patterns with several stationary scale-invariant
      properties. In particular, the patterns display a main patch around the focus of
      spread, with a fractal border structure whose fractal dimension contains
      information about the main statistical properties of the dispersal mechanism. Our
      results are in agreement with field data of spread of invaders with long distance
      dispersal mechanisms.

PMID- 16962618
TI  - A multi-phase mathematical model of quorum sensing in a maturing Pseudomonas
      aeruginosa biofilm.
AB  - It is well known that sessile bacteria have a strong tendency to exist in a
      biofilm phenotype, whereby bacterial cells aggregate and produce a gel-like
      extracellular matrix, which, in an infection scenario, offers a significant
      barrier to attack by conventional antibiotics and the immune system. In this
      paper we develop a multi-phase model of a maturing Pseudomonas aeruginosa
      biofilm, allowing for the production and secretion of exopolysaccharide (EPS).
      The primary quorum-sensing system of P. aeruginosa (namely the lasR system) is
      believed to be required for full biofilm development, and we thus take the
      synthesis of EPS to be regulated by the cognate signal molecule, 3-oxo-C12-HSL.
      We also take EPS and signal production, along with bacterial growth, to be
      limited by oxygen availability, thus factoring in the nutrient poor conditions
      deep inside the biofilm. We use simulations to examine the role played by quorum
      sensing in the biofilm maturation process, and to investigate the effect of anti
      quorum sensing and antibiotic treatments on EPS concentration, signal level,
      bacterial numbers and biofilm growth rate. In addition, we undertake analysis of
      the associated travelling-wave behaviour.

PMID- 16962619
TI  - Visuomotor functions of the posterior parietal cortex.
AB  - In this special issue of Neuropsychologia leading experts in the field discuss
      controversies and advances in the role of the posterior parietal cortex (PPC) in
      visuomotor control. The papers are wide-ranging in their scope, covering monkey
      physiology and anatomy, functional imaging in humans and monkeys as well as
      transcranial magnetic stimulation and lesion studies in humans. The collection
      provides an important overview of the current state-of the-art in this area of
      research, including discussions on homologies between monkey and human parietal
      regions, the role of co-ordinate transformations and intermediate representations
      from vision to action, and reviews of controversial hot topics in this field.

PMID- 16962620
TI  - Sustainable waste management in the UK: the public health role.
AB  - This paper discusses waste management in the UK and its relationship with health.
      It aims to outline the role of health professionals in the promotion of waste
      management, and argues for a change in their role in waste management regulation
      to help make the process more sustainable. The most common definition of
      sustainable development is that by the Brundtland commission, i.e. "development
      that meets the needs of the present without compromising the ability of future
      generations to meet their own needs". Managing waste sites in a manner that
      minimises toxic impacts on the current and future generations is obviously a
      crucial part of this. Although the management of waste facilities is extremely
      complex, the Integrated Pollution Prevention and Control regime, which requires
      the input of public health professionals on the regulation of such sites, means
      that all waste management installations should now be operating in a fashion that
      minimises any toxicological risks to human health. However, the impacts upon
      climate change, resource use and health inequalities, as well as the effects of
      waste transportation, are currently not considered to be part of public health
      professionals' responsibilities when dealing with these sites. There is also no
      requirement for public health professionals to become involved in waste
      management planning issues. The fact that public health professionals are not
      involved in any of these issues makes it unlikely that the potential impacts upon
      health are being considered fully, and even more unlikely that waste management
      will become more sustainable. This paper aims to show that by only considering
      direct toxicological impacts, public health professionals are not fully
      addressing all the health issues and are not contributing towards sustainability.
      There is a need for a change in the way that health professionals deal with waste
      management issues.

PMID- 16962621
TI  - Health impact assessment and community involvement in land remediation decisions.
AB  - This paper describes a collaborative health impact assessment (HIA) of land
      remediation options at the site of a former smokeless fuel factory, where action
      had been delayed by conflict between stakeholders. The likely impacts of the
      processes involved on the physical and mental health of the community were
      examined in terms of the relevant scientific and medical literature, history of
      the site and evidence of local people. Although all remediation options were
      likely to have some adverse health effects, they could be mitigated by making
      choices based on the best evidence. The steering group concluded that the adverse
      effects of remediation would be relatively short term and could be justified by
      the medium- to long-term benefits of removing toxic substances. The HIA steering
      group's recommendations were accepted by the project working group, resulting in
      the resolution of long-running conflict between the residents, activists and
      those responsible for site remediation, which has now commenced.

PMID- 16962622
TI  - Community support is associated with better antiretroviral treatment outcomes in
      a resource-limited rural district in Malawi.
AB  - A study was carried in a rural district in Malawi among HIV-positive individuals
      placed on antiretroviral treatment (ART) in order to verify if community support
      influences ART outcomes. Standardized ART outcomes in areas of the district with
      and without community support were compared. Between April 2003 (when ART was
      started) and December 2004 a total of 1634 individuals had been placed on ART.
      Eight hundred and ninety-five (55%) individuals were offered community support,
      while 739 received no such support. For all patients placed on ART with and
      without community support, those who were alive and continuing ART were 96 and
      76%, respectively (P<0.001); death was 3.5 and 15.5% (P<0.001); loss to follow-up
      was 0.1 and 5.2% (P<0.001); and stopped ART was 0.8 and 3.3% (P<0.001). The
      relative risks (with 95% CI) for alive and on ART [1.26 (1.21-1.32)], death [0.22
      (0.15-0.33)], loss to follow-up [0.02 (0-0.12)] and stopped ART [0.23 (0.08
      0.54)] were all significantly better in those offered community support
      (P<0.001). Community support is associated with a considerably lower death rate
      and better overall ART outcomes. The community might be an unrecognized and
      largely 'unexploited resource' that could play an important contributory role in
      countries desperately trying to scale up ART with limited resources.

PMID- 16962623
TI  - Availability and metabolism of 77Se-methylseleninic acid compared simultaneously
      with those of three related selenocompounds.
AB  - Nutritional selenocompounds are considered to be transformed into the common
      intermediate selenide for utilization as selenoenzymes and/or for excretion as
      selenosugar and trimethylselenonium (TMSe). Therefore, selenocompounds can only
      be traced with a labeled selenium atom. Methylseleninic (MSA(IV)) has been
      proposed to be a third nutritional selenium source, the other two being inorganic
      selenocompounds and organic selenoamino acids, and to be a proximate
      selenochemical for producing the assumed biologically active form methylselenol.
      Here we applied a new tracer method to compare the availability and metabolism of
      MSA(IV) with those of three related selenocompounds under exactly identical host
      and tracing conditions. (82)Se-Selenite, (78)Se-selenate, (77)Se-MSA(IV) and
      (76)Se-methylselenonic acids (MSA(VI)) were simultaneously administered orally,
      each at the dose of 25 microg Se/kg body weight, to rats that had been depleted
      of endogenous natural abundance selenium with a single stable isotope ((80)Se).
      Time-related changes in the concentrations and/or distributions of the four
      labeled isotopes in the serum, liver, kidney, pancreas, lung and urine were
      determined simultaneously by inductively coupled argon plasma mass spectrometry
      (ICP MS) and/or HPLC-ICP MS. The availability with different isotope ratios was
      in the decreasing order of selenate>selenite=MSA(IV)>MSA(VI). Although selenate
      and MSA(VI) were distributed in organs and urine partly in their intact forms,
      MSA(IV) and selenite were not detected in the intact forms at all. MSA(IV) and
      MSA(VI) but not selenite or selenate produced TMSe in organs other than the
      liver, suggesting the transformation of MSA(IV) into methylselenol, and then
      either into selenide for the synthesis of selenoproteins and selenosugar or
      directly into TMSe. Thus, selenosugar and TMSe were produced widely in the
      organs. However, TMSe was not detected in the liver. The organ- and selenium
      source-specific production of TMSe was discussed as to the differences in
      selenium sources, and demethylation and methylation activity.

PMID- 16962624
TI  - Human adrenocarcinoma (H295R) cells for rapid in vitro determination of effects
      on steroidogenesis: hormone production.
AB  - To identify and prioritize chemicals that may alter steroidogenesis, an in vitro
      screening assay based on measuring alterations in hormone production was
      developed using the H295R human adrenocortical carcinoma cell line. Previous
      studies indicated that this cell line was useful to screen for effects on gene
      expression of steroidogenic enzymes. This study extended that work to measure the
      integrated response on production of testosterone (T), estradiol (E2), and
      progesterone/pregnenolone (P) using an ELISA. Under optimized culture and
      experimental conditions, the basal release of P, T and E2 into the medium was
      7.0+/-1.2 ng/ml, 1.6+/-0.4 ng/ml, and 0.51+/-0.13 ng/ml, respectively. Model
      chemicals with different modes of action on steroidogenic systems were tested.
      Exposure to forskolin resulted in dose-dependent increases in all three hormones
      with the greatest relative increase being observed for E2. This differed from
      cells exposed to prochloraz or ketoconazole where P concentrations increased
      while T and E2 concentrations decreased in a dose-dependent manner. In cells
      exposed to fadrozole, E2 decreased in a dose-dependent manner while T and P only
      decreased at the greatest dose tested. Aminoglutethimide decreased P and E2
      concentrations but increased T concentrations. Vinclozolin reduced both P and T
      but resulted in a slight increase in E2. The alteration in the patterns of
      hormone production in the H295R assay was consistent with the modes of action of
      the chemicals and was also consistent with observed effects of these chemicals in
      animal models. Based on these results, the H295R in vitro system has potential
      for high throughput screening to not only characterize the effects of chemicals
      on endocrine systems but also to prioritize chemicals for additional testing.

PMID- 16962625
TI  - Establishment of a protocol for the gene expression analysis of laser
      microdissected rat kidney samples with affymetrix genechips.
AB  - Laser microdissection in conjunction with microarray technology allows selective
      isolation and analysis of specific cell populations, e.g., preneoplastic renal
      lesions. To date, only limited information is available on sample preparation and
      preservation techniques that result in both optimal histomorphological
      preservation of sections and high-quality RNA for microarray analysis.
      Furthermore, amplification of minute amounts of RNA from microdissected renal
      samples allowing analysis with genechips has only scantily been addressed to
      date. The objective of this study was therefore to establish a reliable and
      reproducible protocol for laser microdissection in conjunction with microarray
      technology using kidney tissue from Eker rats p.o. treated for 7 days and 6
      months with 10 and 1mg Aristolochic acid/kg bw, respectively. Kidney tissues were
      preserved in RNAlater or snap frozen. Cryosections were cut and stained with
      either H&E or cresyl violet for subsequent morphological and RNA quality
      assessment and laser microdissection. RNA quality was comparable in snap frozen
      and RNAlater-preserved samples, however, the histomorphological preservation of
      renal sections was much better following cryopreservation. Moreover, the
      different staining techniques in combination with sample processing time at room
      temperature can have an influence on RNA quality. Different RNA amplification
      protocols were shown to have an impact on gene expression profiles as
      demonstrated with Affymetrix Rat Genome 230_2.0 arrays. Considering all the
      parameters analyzed in this study, a protocol for RNA isolation from laser
      microdissected samples with subsequent Affymetrix chip hybridization was
      established that was also successfully applied to preneoplastic lesions laser
      microdissected from Aristolochic acid-treated rats.

PMID- 16962626
TI  - Stings of edible jellyfish (Rhopilema hispidum, Rhopilema esculentum and
      Nemopilema nomurai) in Japanese waters.
AB  - Three edible jellyfish Rhopilema hispidum, R. esculentum and Nemopilema nomurai
      are virulent to humans. We monitored one patient that was stung sequentially by
      these three species of jellyfish. The first species caused a persistent eruption,
      the second produced significant pruritus and the last induced only cutaneous
      symptoms rather than severe systemic disorders reported for its Chinese
      counterpart. The lesions of these jellyfish species are characteristic and common
      in workers harvesting medusae. There is no significant incidence of symptoms by
      ingesting these animals.

PMID- 16962627
TI  - Discovery of novel [Arg49]phospholipase A2 isozymes from Protobothrops elegans
      venom and regional evolution of Crotalinae snake venom phospholipase A2 isozymes
      in the southwestern islands of Japan and Taiwan.
AB  - Protobothrops (formerly Trimeresurus) elegans, a Crotalinae snake, inhabits
      Ishigaki and Iriomote islands of the Sakishima Islands of Japan which are located
      between Okinawa island of Japan and Taiwan. Two phospholipase A(2) (PLA(2))
      isozymes were purified to homogeneity from P. elegans venom and sequenced. This
      led to a discovery of novel PLA(2) isozymes with Arg at position 49, that is,
      [Arg(49)]PLA(2) forms, named PeBP(R)-I and PeBP(R)-II. They are polymorphic at
      position 3, Val for PeBP(R)-I and Ile for PeBP(R)-II. The cDNAs encoding PeBP(R)
      I and PeBP(R)-II were cloned. The cDNA encoding an [Asp(49)]PLA(2) named PePLA(2)
      was also obtained. In contrast to PLA(2) isozymes from Protobothrops genus with
      122 amino acid residues, PeBP(R)-I and PeBP(R)-II are composed of 121 amino acid
      residues due to lack of Pro at position 90. They exhibited necrotic and edema
      inducing activities but no hemorrhagic activity was detected. A phylogenetic tree
      constructed for venom PLA(2) isozymes of Protobothrops genus and of related
      genera in the southwestern islands of Japan and Taiwan revealed that PeBP(R)-I
      and PeBP(R)-II of P. elegans are evolutionarily much closer to PmK49PLA(2), a
      [Lys(49)]PLA(2), from P. mucrosquamatus (Taiwan) than BPI and BPII, both
      [Lys(49)]PLA(2) forms, from P. flavoviridis (Amami-Oshima and Tokunoshima islands
      of Japan). Such evolutionary relationships are also seen in neutral
      [Asp(49)]PLA(2) isozymes from the three Protobothrops species. Thus, P. elegans
      is the species much closer to P. mucrosquamatus than P. flavoviridis. Their
      evolutionary distances seem to be well related to geological history of the
      islands where they have lived. In addition, it was clearly noted that Ovophis
      okinavensis (Amami-Oshima), which had formerly belonged to the Trimeresurus
      genus, and Trimeresurus stejnegeri (Taiwan) are the species fairly distant from
      Protobothrops genus.

PMID- 16962629
TI  - Comparison of the retinitis pigmentosa mutations in rhodopsin with a functional
      map of the C5a receptor.
AB  - We compare the known retinitis pigmentosa (RP) mutations in rhodopsin with
      mutational data obtained for the complement factor 5a receptor (C5aR), a member
      of the rhodopsin-like family of G protein-coupled receptors (GPCRs). We have
      performed genetic analyses that define residues that are required for C5aR
      folding and function. The cognate residues in rhodopsin are not preferentially
      mutated in RP, suggesting that the predominant molecular defect in RP involves
      more than simple misfolding or inactivation. Energy calculations are performed to
      elucidate the structural effects of the RP mutations. Many of these mutations
      specifically disrupt the environment of the retinal prosthetic group of
      rhodopsin, and these do not correspond to essential residues in C5aR. This may be
      because a retinal group is present in rhodopsin but not in C5aR. Another subset
      of RP mutations is more generally important for receptor structure, and these
      mutations correlate with essential residues of C5aR.

PMID- 16962628
TI  - Ability of herpes simplex virus vectors to boost immune responses to DNA vectors
      and to protect against challenge by simian immunodeficiency virus.
AB  - The immunogenicity and protective capacity of replication-defective herpes
      simplex virus (HSV) vector-based vaccines were examined in rhesus macaques. Three
      macaques were inoculated with recombinant HSV vectors expressing Gag, Env, and a
      Tat-Rev-Nef fusion protein of simian immunodeficiency virus (SIV). Three other
      macaques were primed with recombinant DNA vectors expressing Gag, Env, and a Pol
      Tat-Nef-Vif fusion protein prior to boosting with the HSV vectors. Robust anti
      Gag and anti-Env cellular responses were detected in all six macaques. Following
      intravenous challenge with wild-type, cloned SIV239, peak and 12-week plasma
      viremia levels were significantly lower in vaccinated compared to control
      macaques. Plasma SIV RNA in vaccinated macaques was inversely correlated with
      anti-Rev ELISPOT responses on the day of challenge (P value<0.05), anti-Tat
      ELISPOT responses at 2 weeks post challenge (P value <0.05) and peak neutralizing
      antibody titers pre-challenge (P value 0.06). These findings support continued
      study of recombinant herpesviruses as a vaccine approach for AIDS.

PMID- 16962630
TI  - Biodegradation of persistent polar pollutants in wastewater: comparison of an
      optimised lab-scale membrane bioreactor and activated sludge treatment.
AB  - The biodegradation of selected non-adsorbing persistent polar pollutants (P(3))
      during wastewater (WW) treatment was studied by comparing a lab-scale membrane
      bioreactor (MBR) running in parallel to activated sludge treatment (AST). The
      investigated P(3) are relevant representatives or metabolites from the compound
      classes: pesticides, pharmaceuticals, insect repellents, flame retardants and
      anionic surfactants. Analyses of all these P(3) at low ng L(-1) levels with
      sufficient standard deviations was performed in WW influents and effluents. Non
      degradable micropollutants, such as EDTA and carbamazepine were not eliminated at
      all during WW treatment by any technique. However, the MBR showed significant
      better removals compared to AST for the investigated poorly biodegradable P(3),
      such as diclofenac, mecoprop and sulfophenylcarboxylates. An application of such
      an in terms of sludge retention time optimised MBR may lead to a reduction of
      these P(3) in the watercycle.

PMID- 16962631
TI  - Exploration of remediation of acid rock drainage with clinoptilolite as sorbent
      in a slurry bubble column for both heavy metal capture and regeneration.
AB  - Preliminary work was carried out to explore a novel process for high-efficiency
      high-capacity remediation of acid rock drainage. Zn and other metal ions were
      adsorbed and desorbed in a laboratory Plexiglas slurry bubble column with natural
      clinoptilolite particles as sorbent. The results indicate that both adsorption
      and desorption in this medium have considerable advantages over those in the
      packed beds and rotating columns, leading to faster batch adsorption and
      desorption, as well as greater uptake of zinc. The adsorption order of
      clinoptilolite particles to different metal ions appeared to be Fe>Al>Cu>Zn>Mg>Mn
      on the basis of normalized concentrations. Smaller particles had significantly
      higher capacity and rates of the adsorption than larger particles for the same
      operating conditions.

PMID- 16962632
TI  - Remediation of PCB contaminated soils using iron nano-particles.
AB  - In this study, iron nano-particles were used to remediate PCB contaminated soil
      and an attempt was made to maximize PCB destruction in each treatment step. The
      results show that nano-particles do aid in the dechlorination process and high
      PCB destruction efficiencies can be achieved. The destruction efficiency during
      the preliminary treatment (mixing of soil and iron nano-particles in water) can
      be increased by increasing the water temperature. The maximum thermal destruction
      (pyrolysis/combustion of soil after preliminary treatment) of soil-bound PCBs
      occurs at 300 degrees C in air. A minimum total PCB destruction efficiency of 95%
      can be achieved by this process. The effect of changing treatment parameters such
      as type of mixing, time of mixing and mixing conditions and application of other
      catalysts like iron oxide and V(2)O(5)/TiO(2) was also investigated. It was found
      that at 300 degrees C in air, iron oxide and V(2)O(5)/TiO(2) are also good
      catalysts for remediating PCB contaminated soils.

PMID- 16962633
TI  - Aerobic degradation of di- and trichlorobenzenes by two bacteria isolated from
      polluted tropical soils.
AB  - Two polychlorinated biphenyl (PCBs)-degrading bacteria were isolated by
      traditional enrichment technique from electrical transformer fluid (Askarel)
      contaminated soils in Lagos, Nigeria. They were classified and identified as
      Enterobacter sp. SA-2 and Pseudomonas sp. SA-6 on the basis of 16S rRNA gene
      analysis, in addition to standard cultural and biochemical techniques. The
      strains were able to grow extensively on dichloro- and trichlorobenzenes.
      Although they failed to grow on tetrachlorobenzenes, monochloro- and
      dichlorobenzoic acids, they were able to utilize all monochlorobiphenyls, and
      some dichlorobiphenyls as sole sources of carbon and energy. The effect of
      incubation with axenic cultures on the degradation of 0.9 mM 1,4-dichlorobenzene,
      0.44 mM 1,2,3- and 0.43 mM 1,3,5-trichlorobenzene in mineral salts medium was
      studied. Approximately, 80-90% of these xenobiotics were degraded in 200 h,
      concomitant with cell increase of up to three orders of magnitude, while
      generation times ranged significantly (P<0.05) from 17-32 h. Catechol 1,2
      dioxygenase and catechol 2,3-dioxygenase activities were detected in crude cell
      free extracts of cultures pre-grown with benzoate, with the latter enzyme
      exhibiting a slightly higher activity (0.15-0.17 micromolmin(-1) mg of protein(
      1)) with catechol, suggesting that the meta-cleavage pathway is the most readily
      available catabolic route in the SA strains. The wider substrate specificity of
      these tropical isolates may help in assessing natural detoxification processes
      and in designing bioremediation and bioaugmentation methods.

PMID- 16962634
TI  - Ammonia triggers the promotion of oxidative stress in the aquatic macrophyte
      Myriophyllum mattogrossense.
AB  - The effect of increased ammonia content on sub-acute biochemical responses was
      assessed in the rooted submersed aquatic macrophyte Myriophyllum mattogrossense
      (common name: "Brazil Milfoil" or "Matogrosso Milfoil"), in a seven day aquarium
      experiment. The pH and temperature were monitored in order to determine the
      proportions of both ionized (NH4+) and un-ionized (NH3) forms of ammonia.
      Specific activities of several enzymes such as catalase (CAT), guaiacol
      peroxidase (POD), glutathione peroxidase (GPx) and glutathione S-transferase
      (GST's) were measured as well as the content of the soluble antioxidant
      glutathione and lipid peroxidation were determined as these parameters are
      considered as indicators of cell-level disorder. The results showed that ammonia
      is able to generate oxidative stress, expressed through an elevated GSH content
      and the enhancement of CAT, POD, GPx and GST's activities in treatments with
      elevated ammonia content. As the toxic mechanism of ammonia is a complex
      phenomenon, this work adds an additional point of view to explain in parts the
      oxidative stress generating effect of ammonia promoting oxidative stress.
      Additionally the different modes of action proposed by other research groups are
      discussed, thus trying to combine the various points of view.

PMID- 16962635
TI  - Transport of organic contaminants through salinity stratified water masses. A
      microcosm experiment.
AB  - A salt-wedge stratified microcosm, spiked with 31 target analytes, including
      PCBs, organochlorine and organophosphorous pesticides, triazines, organophosphate
      flame retardants and caffeine (an urban wastewater molecular marker), was setup.
      Compound behaviour was monitored during a four week period, by sampling at six
      different levels of the water column, in order to understand the transport and
      loss processes of the different classes of chemical substances. Compound
      transport from one water body to the other has been positively correlated with
      diffusion via their molar volume. Target analytes loss has been positively
      correlated with evaporation via their K(H) and with degradation via their halve
      lives. From these two processes, evaporation was found to be predominant using a
      multiparametric regression.

PMID- 16962636
TI  - Degradation of tetraphenylphosphonium bromide at high pH and its effect on
      radionuclide solubility.
AB  - Recently, tetraphenylphosphonium bromide (TPPB) has been used to remove
      technetium from some radioactive waste streams. However, before TPPB could be
      approved for use it was necessary to show that TPPB and its degradation products
      would not have a significant detrimental effect on post-closure performance of a
      radioactive waste repository. TPPB is known to be stable at neutral pH, however,
      under alkaline conditions it degrades by an alkaline hydrolysis mechanism to
      triphenylphosphonium oxide (TPPO). Degradation can also occur by radiolysis to
      produce triphenylphosphine (TPP). The kinetics of the alkaline hydrolysis
      degradation of TPPB is described and the solubility of europium, iodine, nickel,
      technetium(VII) and uranium(VI) in aqueous solutions of TPPB and its degradation
      products is reported. These results were used to support the use of TPPB in
      removing technetium from some waste streams.

PMID- 16962637
TI  - Concentration of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans
      and dioxin-like PCBs in human adipose tissue from Turkish men.
AB  - There is no previous report from Turkey on chemically determined polychlorinated
      dibenzo-para-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin
      like polychlorinated biphenyls (PCBs) in human tissues expressed as World Health
      Organization (WHO) toxic equivalents (TEQs). The objective of this study was to
      determine the occurrence of PCDDs/Fs, and dioxin-like PCBs in the general adult
      Turkish population. For this reason we measured adipose tissue concentrations of
      PCDDs/Fs and dioxin-like PCBs in 23 Turkish men living in Ankara,Turkey in 2004.
      PCDD/F concentrations ranged between 3.2 and 19.7 pg WHO-TEQ/g fat (5.34 and 42.7
      WHO-TEQ/g fat, respectively, including dioxin-like PCBs). The mean concentrations
      of WHO(PCDD/F)-TEQ and WHO(PCB)-TEQ were 9.2 and 6.67 pg/g on a lipid basis ,
      respectively. Samples were analyzed for PCDD/F and twelve dioxin-like PCB
      congeners using high resolution gas chromatography/high resolution mass
      spectrometry (HRGC/HRMS). This study is very important since it is the first
      report on PCDDs/Fs and dioxin-like PCB contamination in human adipose tissue from
      Turkey.

PMID- 16962638
TI  - Pilot survey monitoring pharmaceuticals and related compounds in a sewage
      treatment plant located on the Mediterranean coast.
AB  - A one-year monitoring study was performed to evaluate the occurrence, persistence
      and fate of a group of 14 organic compounds in a sewage treatment plant (STP)
      located in the south of Spain. These results are part of a more extensive study,
      financed by the Spanish Ministry of Research with the aim to evaluate the
      traceability of new pollutants on the Mediterranean coast and to determine the
      removal efficiency of sewage treatment plants (STP) for these pollutants. The
      compounds which have been analyzed include pharmaceuticals of various therapeutic
      categories (ibuprofen, acetaminophen, dipyrone, diclofenac, carbamazepine and
      codeine), pesticides (chlorfenvinfos and permethrin), caffeine, triclosan,
      bisphenol A and three of their more relevant metabolites (1,7-dimethylxanthine,
      carbamazepine 10,11-epoxide and 2,7/2,8-dichlorodibenzo-p-dioxin). An SPE/GC-MS
      multi-residue analytical method was developed and validated to facilitate
      simultaneous determination of these compounds in both influent and effluent
      wastewater. The method provided mean recoveries higher than 75%, with the
      exception of 2,7/2,8-dichlorodibenzo-p-dioxin, dipyrone and permethrin which
      exhibited recoveries lower than 22%. The overall variability of the method was
      below 14%. The method detection limit (LOD) was between 1 and 100 ng l(-1) and
      precision, which was calculated as relative standard deviation (RSD), ranged from
      1.8% to 11.2%. The application of the proposed method has allowed the
      identification of all the target compounds at mean concentrations which ranged
      from 0.12 to 134 microg l(-1) in the influent and from 0.09 to 18.0 microg l(-1)
      in the effluent. The removal efficiencies of the STP for these compounds varied
      from 20% (carbamazepine) to 99% (acetaminophen), but in all cases resulted
      insufficient in order to avoid their presence in treated water and subsequently
      in the environment.

PMID- 16962639
TI  - Polycyclic aromatic hydrocarbons in marine organisms from the Adriatic Sea,
      Italy.
AB  - Polycyclic aromatic hydrocarbons (PAHs) were analyzed in bivalves (Mitylus
      galloprovincialis), cephalopods (Todarodes sagittatus), crustaceans (Nephrops
      norvegicus) and fish (Mullus barbatus, Scomber scombrus, Micromesistius
      poutassou, Merluccius merluccius) in several pools coming from the Central
      Adriatic Sea. These marine organisms were selected because of their multitude,
      wide distribution and common use in the Italian diet, they were sampled and
      analyzed during the year 2004. Acenaphthene, benzo(a)pyrene,
      dibenz(a,h)anthracene, benzo(ghi)perylene and indeno(1,2,3-cd)pyrene showed
      levels below the instrumental detection limit in all samples. Fluorene,
      phenanthrene, anthracene, fluoranthene, benz(a)anthracene, benzo(b)fluoranthene
      and benzo(k)fluoranthene were detected at different concentrations in analyzed
      samples. Chrysene was detected only in mussels with very low values (average
      0.74ngg(-1) wet weight). PAHs composition pattern was dominated by the presence
      of PAHs with 3-rings (62%) followed from those with 4-rings (37%) and 5-rings
      (1%). Atlantic mackerel, European hake and blue whiting showed the highest PAH
      concentrations, ranging from 44.1 to 63.3ngg(-1) wet weight, the group of
      invertebrate organisms showed a level of contamination about three times lower
      than those of the vertebrate groups. Mediterranean mussels that did not present
      very high levels of contamination expressed as sum of PAHs showed one of the
      highest values of benzo(a)pyrene equivalents (BaPEs). Conversely the latter value
      was very low in Atlantic mackerel even if this species reported the highest total
      PAH concentrations. No significant correlation was observed between weight,
      length and trophic levels and total PAHs.

PMID- 16962640
TI  - Influence of humic substances on the photolysis of aqueous pesticide residues.
AB  - The present work investigated the direct and indirect photolysis of pesticide
      residues (atrazine, imazaquin, iprodione), in aqueous solutions and under UV
      visible radiation (280-480nm). Different kinds of humic substances (HS) were
      added to samples in order to evaluate their behaviour as possible photocatalysts
      and their effect on the photolysis of pesticides. The fulvic acids were purchased
      from the International Humic Substances Society, and they were added to samples
      in concentrations ranging from 1 to 150 mgl(-1). Titanium dioxide was used as the
      photocatalyst, in concentration ranging from 10 to 150 mgl(-1). Pesticides
      photolysis were measured by UV-visible absorption spectroscopy and differential
      pulse polarography with all used pesticides, reaching total degradation after 2h
      of irradiation, thus indicating a fast direct photolysis. Photocatalysis by
      TiO(2) could increase the pesticides photolysis rate up to 40%. This effect,
      however, was not observed for imazaquin photolysis. Again, except for imazaquin,
      HS presence showed a positive effect in increasing pesticide degradation, but
      only within specific concentration ranges (below 10mg l(-1) for iprodione and
      about 30mgl(-1) for atrazine). Above these ranges HS induce a decrease in the
      pesticides photolysis rate. Spin-trapping measurements by electronic paramagnetic
      resonance spectroscopy, using the spin-trap DMPO, showed that HS are able to
      photogenerate hydroxyl radicals, increasing the pesticides molecule degradation.
      However, the HS also react with the photogenerated hydroxyl radical, influencing
      the pesticide photolysis, leading to a decrease in the photolysis rate and
      causing it to be strongly dependent on the nature and concentration of residues
      in the water to be treated.

PMID- 16962641
TI  - Photo-induced degradation of diuron in aqueous solution by nitrites and nitrates:
      kinetics and pathways.
AB  - The photo-induced degradation of diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea)
      in aqueous solution under simulated solar irradiation has been investigated in
      the presence of NO3-/NO2- ions. The degradation rates were compared by varying
      environmental parameters including substrate and inducer concentrations, oxygen
      content and pH. The photoproducts were identified by extensive LC-ESI-MS and LC
      ESI-MS-MS studies after SPE preconcentration on prepacked cartridges. In both NO3
      and NO2- conditions, oxidation of the N-(CH3)2 terminus group is the main
      process leading to the N-monodemethylated (NHCH3), N-formyl (N(CH3)CHO) and the
      uncommon and unstable carbinolamine (N(CH3)CH2OH) by-products. Cl/OH substituted
      and nitrated phenylureas are formed minorily. Degradation pathways involving OH*
      and NO2* (or dimer) radicals as reactive species are proposed.

PMID- 16962642
TI  - QSPR/QSAR models for prediction of the physicochemical properties and biological
      activity of polybrominated diphenyl ethers.
AB  - Polybrominated diphenyl ethers (PBDEs) are a group of important persistent
      organic pollutants. In the present study, geometrical optimization and
      electrostatic potential calculations have been performed for all 209 PBDE
      congeners at the HF/6-31G level of theory. A number of statistically-based
      parameters have been obtained. Linear relationships between gas-chromatographic
      relative retention time (RRT), n-octanol/air partition coefficient (lgK(OA)), 298
      K supercooled liquid vapour pressures (lgp(L)), Henry's law constant (lgH) and Ah
      receptor binding affinity (-lgRBA) of PBDEs and the structural descriptors have
      been established by multiple regression method. The result shows that the
      quantities derived from electrostatic potential V(s,max),V(s,min),Pi, Sigma
      V+(S), V-(S) , nu, sigma 2(tot), and N-(v), together with the molecular volume
      (Vmc) can be well used to express the quantitative structure-property
      relationships of PBDEs, which proves the general applicability of this parameter
      set to a great extent. Good predictive capabilities have also been demonstrated.
      Based on these equations, the predicted values have been presented for those PBDE
      congeners whose experimentally determined physicochemical properties are
      unavailable. The QSAR model for the Ah receptor binding affinity is relatively
      poor, which can be ascribed to the complexity of factors which affect biological
      activity and the limitations of the present parameter set in describing steric
      characters of the molecule.

PMID- 16962643
TI  - Severe wear and tooth loss in wild ring-tailed lemurs (Lemur catta): a function
      of feeding ecology, dental structure, and individual life history.
AB  - The ring-tailed lemurs at Beza Mahafaly Special Reserve, Madagascar, exhibit a
      high frequency of severe wear and antemortem tooth loss. As part of a long-term
      study, we collected dental data on 83 living adult ring-tailed lemurs during 2003
      and 2004. Among these individuals, 192 teeth were scored as absent. The most
      frequently missing tooth position is M1 (24%). As M1 is the first tooth to erupt,
      its high frequency of absence (primarily a result of wear) is not remarkable.
      However, the remaining pattern of tooth loss does not correlate with the sequence
      of eruption. We suggest that this pattern is a function of 1) feeding ecology, as
      hard, tough tamarind fruit is a key fallback food of ring-tailed lemurs living in
      gallery forests; 2) food processing, as tamarind fruit is primarily processed in
      the P3-M1 region of the mouth; and 3) tooth structure, as ring-tailed lemurs
      possess thin dental enamel. The incongruity between thin enamel and use of a
      hard, tough fallback food suggests that ring-tailed lemurs living in riverine
      gallery forests may rely on resources not used in the past. When comparing dental
      health in the same individuals (n=50) between 2003 and 2004, we found that
      individual tooth loss can show a rapid increase over the span of one year,
      increasing by as much as 20%. Despite this rapid loss, individuals are able to
      survive, sometimes benefiting from unintentional assistance from conspecifics,
      from which partially processed tamarind fruit is obtained. Although less frequent
      in this population, these longitudinal data also illustrate that ring-tailed
      lemurs lose teeth due to damage and disease, similar to other nonhuman primates.
      The relationship between tooth loss, feeding ecology, dental structure, and
      individual life history in this population has implications for interpreting
      behavior based on tooth loss in the hominid fossil record.

PMID- 16962644
TI  - Questionnaire survey of exposure to lead in the domestic environment in Nigeria.
AB  - Environmental exposure to lead is a significant cause of morbidity and mortality
      in developed countries, particularly in children, but remains understudied in
      developing countries. While prevention is acknowledged as the best public health
      option, the level of knowledge about lead exposure in many developing countries
      is not known. We conducted a survey to evaluate the knowledge about lead exposure
      in Nigeria. Survey questionnaires were developed from the results of focus group
      discussions and published literature. 600 questionnaires were randomly
      distributed to adults living in Ibadan, South Western Nigeria in 2004. In
      addition, the knowledge of lead exposure was measured using a modified version of
      the Chicago Lead Knowledge Test (CLKT). Information on lead abatement and sources
      of household lead exposure were also obtained. Most respondents did not have a
      satisfactory level of knowledge about lead exposure in the domestic environment,
      how to prevent it and the role of nutrition in diminishing the impact of
      exposure. Younger people, female and increased years of schooling predict higher
      scores in the CLKT. Most respondents lived in rented homes; the majority of which
      were either built or last refurbished in the 1990s. Home owners and people living
      in homes built or last refurbished within 4 years of the study had higher mean
      CLKT scores. Our study showed that our respondents had very low levels of
      knowledge about the risk of domestic exposure to lead, particularly to children.
      We recommend that efforts should be made to increase awareness of this condition
      and that in Nigeria as in most development countries; this should be done through
      the maternal and child health care programs.

PMID- 16962645
TI  - Freeze-dried whole plasma: evaluating sucrose, trehalose, sorbitol, mannitol and
      glycine as stabilizers.
AB  - Several groups report stability results for freeze-dried whole plasma intended
      for use as a transfusion product [Hellstern P, Sachse H, Schwinn H, Oberfrank K.
      Manufacture and in vitro characterization of a solvent/detergent-treated human
      plasma. Vox Sang 1992;63:178-185; Trobisch H. Results of a quality-control study
      of lyophilized pooled plasmas which have been virally inactivated using a solvent
      detergent method (modified Horowitz procedure). Beitr Infusionsther 1991;28:92
      109; Hugler P, Trobish H, Neuman H, Moller, Sirtl C, Derdak M, Laubenthal H.
      Quality control of three different conventional fresh-frozen plasma preparations
      and one new virus-inactivated lyophilized pooled plasma preparation. Klin
      Wochenschr 1991;69:157-161; Krutvacho T, Chuansumrit A, Isarangkura P, Pintadit
      P, Hathirat P, Chiewsilp P. Response of hemophilia with bleeding to fresh dry
      plasma. Southeast Asian J Trop Med Public Health 1993;24:169-173; Chuansumrit A,
      Krasaesub S, Angchaisuksiri P, Hathirat P, Isarangkura P. Survival analysis of
      patients with haemophilia at the International Haemophilia Training Centre,
      Bangkok, Thailand. Haemophilia 2004;10:542-549]. Plasma coagulation properties
      are substantially impaired in these freeze-dried plasmas, while pH levels are
      close to alkaline. In this work, plasma supplemented with 60mM sucrose,
      trehalose, mannitol, sorbitol or glycine was freeze-dried. The samples were
      subjected to forced degradation at 40 degrees C for 10 days in order to quickly
      evaluate the effectiveness of the different stabilizers. Initial PT, APTT and TT
      values were 14.4+/-0. 5s, 31.4+/-1.5s and 18.3+/-0.6s, respectively. At the end
      of the degradation period, PT, APTT and TT were substantially prolonged, and were
      19.1+/-0. 5s, 43.1+/-0.6s and 26.1+/-1.0s, respectively. In the presence of
      glycine, at the end of the degradation period, PT, APTT and TT values remained
      close to the initial values and were 15.5+/-0. 4s, 35.7+/-0.9s and 19.4+/-0.2s,
      respectively. Percent activities of the coagulation factors V, VII, VIII, IX, X
      and the coagulation inhibitors protein C, protein S and antithrombin III were
      recorded. Factors V and VIII were most prone to degradation. Factor V and VIII
      activities, in control plasma, were approx. 44+/-3.5% and 58+/-2.3%, at the end
      of storage. In contrast, much higher factor V and VIII activities were maintained
      in the lyophilized glycine-supplemented plasma: approx. 60+/-3.5% and 74+/-7.0%,
      correspondingly. The most stable protein was protein C, which showed no signs of
      degradation under the testing conditions of this study. All tested stabilizers
      provided protection. Glycine, however, outperformed all tested polyols, providing
      superior preservation of plasma clotting properties. Thermograms of 60mM glycine
      in water and 60mM glycine in plasma show that, in the presence of plasma, glycine
      does not crystallize. The process of freeze-drying caused a complete loss of
      plasma pCO(2) (gas) and a substantial increase in plasma pH. Citric acid was
      found to be a suitable pH adjuster for lyophilized/rehydrated plasma.

PMID- 16962646
TI  - Changes in the extracellular matrix in periurethral tissue of women with stress
      urinary incontinence.
AB  - Changes in structural support of the urethra and bladder neck have been proposed
      as important factors in the pathogenesis of stress urinary incontinence (SUI). In
      this context, we undertook an ultrastructural study on the periurethral
      connective tissue with an emphasis on incontinent women with normotonic and
      hypotonic urethras. Small specimens of periurethral connective tissue were
      obtained by dissection during a tension-free vaginal tape-implantation procedure
      in 34 stress urinary incontinent postmenopausal women with a normotonic urethra
      and 9 stress urinary incontinent postmenopausal women with a hypotonic urethra.
      In the samples taken from stress-incontinent women with a normotonic urethra,
      intact elastic fibers were closely connected with collagen fibers, smooth muscle
      cells and fibrocytes. In the samples taken from stress-incontinent women with a
      hypotonic urethra, we detected irregular fragmented distribution of the elastin
      within the tissue. We assume that these structural changes lead to functional
      consequences, such as diminished tissue extensibility and loss of stability
      surrounding the female urethra. These altered connective tissue properties may
      affect the mechanism of urethral closure under stress (e.g., coughing) and
      therefore contribute to the occurrence of SUI with a hypotonic urethra.

PMID- 16962647
TI  - Palatal fusion - where do the midline cells go? A review on cleft palate, a major
      human birth defect.
AB  - Formation of the palate, the organ that separates the oral cavity from the nasal
      cavity, is a developmental process characteristic to embryos of higher
      vertebrates. Failure in this process results in palatal cleft. During the final
      steps of palatogenesis, two palatal shelves outgrowing from the sides of the
      embryonic oronasal cavity elevate above the tongue, meet in the midline, and
      rapidly fuse together. Over the decades, multiple mechanisms have been proposed
      to explain how the superficial mucous membranes disappear from the contact line,
      thus allowing for normal midline mesenchymal confluence. A substantial body of
      experimental evidence exists for cell death, cell migration, epithelial-to
      mesenchymal transdifferentiation (EMT), replacement through new tissue
      intercalation, and other mechanisms. However, the most recent use of gene
      recombination techniques in cell fate tracking disfavors the EMT concept, and
      suggests that apoptosis is the major fate of the midline cells during
      physiological palatal fusion. This article summarizes the benefits and drawbacks
      of histochemical and molecular tools used to determine the fates of cells within
      the palatal midline. Mechanisms of normal disintegration of the midline
      epithelial seam are reviewed together with pathologic processes that prevent this
      disintegration, thus causing cleft palate.

PMID- 16962648
TI  - The risk of endometrial cancer in women with BRCA1 and BRCA2 mutations. A
      prospective study.
AB  - OBJECTIVE: To evaluate the risk of endometrial cancer in women who carry a
      deleterious mutation in the BRCA1 or BRCA2 genes. PATIENTS AND METHODS: Women
      known to carry a BRCA1 or BRCA2 mutation, aged 45 to 70, were identified from an
      international registry and were followed prospectively. A total of 857 women
      completed a baseline questionnaire and one or more follow-up questionnaires.
      Study subjects were followed until diagnosis of endometrial cancer, ovarian
      cancer, death or the date of completion of the last questionnaire. The expected
      number of endometrial cancers was calculated using age and country-specific
      incidence rates. RESULTS: After an average follow-up period of 3.3 years, six
      women were diagnosed with endometrial cancer, compared to 1.13 cancers expected
      (SIR=5.3, p=0.0011). Four of these six patients used tamoxifen in the past. The
      risk among women who were never exposed to tamoxifen treatment was not
      significantly elevated (SIR=2.7, p=0.17), but among the 226 participants who had
      used tamoxifen (220 as treatment and six for the primary prevention of breast
      cancer) the relative risk for endometrial cancer was 11.6 (p=0.0004). CONCLUSION:
      The main contributor to the increased risk of endometrial cancer among BRCA
      carriers is tamoxifen treatment for a previous breast cancer. The risk and
      benefits of prophylactic hysterectomy should be discussed with women with a BRCA
      mutation considering tamoxifen therapy.

PMID- 16962649
TI  - Clozapine markedly elevates pregnenolone in rat hippocampus, cerebral cortex, and
      serum: candidate mechanism for superior efficacy?
AB  - Clozapine demonstrates superior efficacy in patients with schizophrenia, but the
      precise mechanisms contributing to this clinical advantage are not clear.
      Clozapine and olanzapine increase the GABAergic neuroactive steroid (NS)
      allopregnanolone, and it has been hypothesized that NS induction may contribute
      to the therapeutic actions of these agents. Pregnenolone administration improves
      learning and memory in rodent models, and decreases in this NS have been
      associated with depressive symptoms in humans. These pregnenolone characteristics
      may be relevant to the actions of antipsychotics. We therefore investigated
      potential pregnenolone alterations in rat hippocampus and cerebral cortex
      following clozapine, olanzapine, and other second generation agents as a
      candidate NS mechanism contributing to antipsychotic efficacy. In the first set
      of experiments, intact, adrenalectomized, and sham-operated male rats received
      vehicle or clozapine (20 mg/kg) IP. In the second set, male rats received
      vehicle, olanzapine (5 mg/kg), quetiapine (20 mg/kg), ziprasidone (10 mg/kg) or
      aripiprazole (5 mg/kg) IP. Pregnenolone levels were determined by gas
      chromatography/mass spectrometry. Clozapine markedly elevates pregnenolone in rat
      hippocampus, cerebral cortex, and serum; hippocampal levels were strongly
      correlated with serum levels (r=0.987). Olanzapine also elevates pregnenolone
      levels, but to a lesser degree than clozapine. Pregnenolone induction may
      contribute to the clinical actions of clozapine and olanzapine.

PMID- 16962650
TI  - Effects of osemozotan, ritanserin and azasetron on cocaine-induced behavioral
      sensitization in mice.
AB  - Repeated intermittent administration of psychostimulants causes behavioral
      sensitization in rodents. Previous studies using serotonin (5-HT) receptor
      ligands show that the 5-HT system is involved in cocaine-induced behavioral
      sensitization in rats, but the role of the 5-HT system has not been studied in
      mice. The present study examined the effects of the 5-HT(1A) receptor agonist
      osemozotan, the 5-HT(2) receptor antagonist ritanserin and the 5-HT(3) receptor
      antagonist azasetron on cocaine-induced behavioral sensitization in male ddY
      mice. Repeated administration of cocaine for 7 days enhanced cocaine-induced
      locomotor activity, and this sensitization was observed even after withdrawal for
      7-14 days. Cocaine-induced behavioral sensitization after a 7-day withdrawal was
      significantly reduced with the coadministration of osemozotan, ritanserin or
      azasetron with cocaine repeatedly for 7 days. A single injection of osemozotan or
      ritanserin before cocaine challenge also reduced repeated cocaine-induced
      behavioral sensitization. However, none of these ligands inhibited cocaine
      induced behavioral sensitization, when each drug was administered for 7 days
      after repeated cocaine administration. These results suggest that the central 5
      HT system plays a role in the development and expression, but not maintenance, of
      behavioral sensitization in cocaine-treated mice.

PMID- 16962651
TI  - Neurosteroids, neuroactive steroids, and symptoms of affective disorders.
AB  - Neurosteroids (NS) are steroids synthesized by the brain. Neuroactive steroids
      (NAS) refers to steroids that, independent of their origin, are capable of
      modifying neural activities. NAS bind and modulate different types of membrane
      receptors. The gamma amino butyric acid (GABA) and sigma receptor complexes have
      been the most extensively studied. Oxidized ring A reduced pregnanes,
      tetrahydroprogesterone (THP), and tetrahydrodeoxycorticosterone (THDOC) bind to
      the progesterone intracellular receptor (PR), and in this way can also regulate
      gene expression. Animal experimentation showed that salient symptoms of
      depression, viz., anxiety, sleep disturbances, and memory and sexual
      dysfunctions, are modulated by NAS. In turn, psychotropic drugs modulate NS and
      NAS levels. NS levels as well as NAS plasma concentrations change in patients
      with depression syndromes, the levels return to normal baseline with recovery,
      but normalization is not necessary for successful therapy. Results from current
      studies on the evolution of nervous systems, including evolutionary developmental
      biology as well as anatomical and physiological findings, almost preclude a
      categorical classification of the psychiatric ailments the human brain succumbs
      to. The persistence in maintaining such essentialist classifications may help to
      explain why up to now the search for biological markers in psychiatry has been an
      unrewarding effort. It is proposed that it would be more fruitful to focus on
      relationships between NAS and symptoms of psychiatric disorders, rather than with
      typologically defined disorders.

PMID- 16962652
TI  - Patient navigation and case management following an abnormal mammogram: a
      randomized clinical trial.
AB  - BACKGROUND: A high rate of low-income, ethnic minority women delay or fail to
      keep appointments following abnormal mammograms. This study was designed to test
      the effectiveness of a structured counseling and patient navigation intervention
      for improving follow-up rates at a large public sector medical center. METHODS:
      This randomized clinical trial, conducted in Los Angeles 2001-2002, included 204
      women with abnormal mammograms referred for follow-up who were then assigned to
      intervention or usual care. The primary outcome was the rate of follow-up through
      diagnostic resolution within eight months. RESULTS: The intervention resulted in
      a significant increase in the rate of adherence to follow-up through diagnostic
      resolution. The intervention group was much more likely to be adherent through
      diagnostic resolution than the control group (90% vs. 66%, OR=4.48, p<0.001) and
      were more likely to experience timely adherence than UC patients (77% vs. 57%,
      OR=2.5, p=0.01). Intervention effectiveness was not significantly different for
      women assigned to different levels of service intensity. CONCLUSIONS: Patient
      navigation and counseling driven by a structured clinical algorithm are highly
      effective strategies to improve diagnostic resolution follow-up among low-income,
      ethnic minority women with abnormal mammograms. The intervention algorithm and
      available training materials can be adapted for diverse care systems serving high
      risk women to decrease loss to follow-up.

PMID- 16962654
TI  - Crystal structure of a 70S ribosome-tRNA complex reveals functional interactions
      and rearrangements.
AB  - Our understanding of the mechanism of protein synthesis has undergone rapid
      progress in recent years as a result of low-resolution X-ray and cryo-EM
      structures of ribosome functional complexes and high-resolution structures of
      ribosomal subunits and vacant ribosomes. Here, we present the crystal structure
      of the Thermus thermophilus 70S ribosome containing a model mRNA and two tRNAs at
      3.7 A resolution. Many structural details of the interactions between the
      ribosome, tRNA, and mRNA in the P and E sites and the ways in which tRNA
      structure is distorted by its interactions with the ribosome are seen.
      Differences between the conformations of vacant and tRNA-bound 70S ribosomes
      suggest an induced fit of the ribosome structure in response to tRNA binding,
      including significant changes in the peptidyl-transferase catalytic site.

PMID- 16962653
TI  - SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt
      phosphorylation and substrate specificity.
AB  - Mammalian target of rapamycin (mTOR) controls cell growth and proliferation via
      the raptor-mTOR (TORC1) and rictor-mTOR (TORC2) protein complexes. Recent
      biochemical studies suggested that TORC2 is the elusive PDK2 for Akt/PKB Ser473
      phosphorylation in the hydrophobic motif. Phosphorylation at Ser473, along with
      Thr308 of its activation loop, is deemed necessary for Akt function, although the
      regulatory mechanisms and physiological importance of each phosphorylation site
      remain to be fully understood. Here, we report that SIN1/MIP1 is an essential
      TORC2/PDK2 subunit. Genetic ablation of sin1 abolished Akt-Ser473 phosphorylation
      and disrupted rictor-mTOR interaction but maintained Thr308 phosphorylation.
      Surprisingly, defective Ser473 phosphorylation affected only a subset of Akt
      targets in vivo, including FoxO1/3a, while other Akt targets, TSC2 and GSK3, and
      the TORC1 effectors, S6K and 4E-BP1, were unaffected. Our findings reveal that
      the SIN1-rictor-mTOR function in Akt-Ser473 phosphorylation is required for TORC2
      function in cell survival but is dispensable for TORC1 function.

PMID- 16962655
TI  - Changes in CRP, SAA and haptoglobin produced in response to ovariohysterectomy in
      healthy bitches and those with pyometra.
AB  - The aim of the study was to assess changes in serum C-reactive protein (CRP),
      serum amyloid A component (SAA) and haptoglobin (Hp) concentrations in healthy
      bitches and in those with pyometra undergoing ovariohysterectomy, and to
      establish the usefulness of such determinations for monitoring the postoperative
      period. Our results indicate that CRP and SAA determinations serve to evaluate
      the severity of the inflammatory process in pyometra since the concentrations of
      these acute phase proteins were increased immediately after surgery and
      diminished thereafter. The CRP and SAA response was rapidly produced while Hp
      concentrations increased in a more gradual manner. Thus, postoperative
      concentrations of CRP and SAA provide valuable information on the subsidence of
      the inflammatory response during the uneventful postoperative period. Our
      findings also suggest that acute phase proteins might be useful diagnostic
      markers of early postoperative complications.

PMID- 16962656
TI  - Stereological methods to assess tissue response for tissue-engineered scaffolds.
AB  - The stereological approach can provide an objective unbiased assessment of
      structural change in biological systems. In this review, we elucidate the basic
      principles of stereology and their implementation in the analysis of tissue
      response to tissue-engineering scaffolds. A brief outline of tissue response
      parameters that can be estimated using stereological approach is included. The
      focus is on frequently quantified parameters in tissue response, such as host
      tissue infiltration, inflammatory cell numbers, angiogenesis, fibrous tissue
      thickness, areas of calcification, and/or necrosis, among others. Special
      consideration is given to sampling techniques and how these techniques can
      influence the reliability of the obtained results as well as minimizing potential
      sources of bias. These basic principles are illustrated with practical examples,
      where measurements are performed and estimations calculated using conventional
      stereological techniques. As the next generation of biomaterials continue to be
      developed, it is essential that researchers develop a rigorous and unbiased
      method of performance quantification.

PMID- 16962657
TI  - Disassembly of layer-by-layer films of plasmid DNA and reducible TAT polypeptide.
AB  - This paper reports the disassembly of layer-by-layer (LbL) films of plasmid DNA
      and a reducible cationic polypeptide. To utilize a reducing microenvironment of
      cellular plasma membrane as a potential trigger, LbL films are assembled to
      contain both DNA and the TAT-based polypeptide (PTAT) with reducible disulfide
      bonds in the backbone. The assembly and disassembly processes are monitored by
      goniometry, ellipsometry, and atomic force microscopy (AFM). The structure of the
      PTAT films is compared with that of non-reducible poly(L-lysine) (PLL) films.
      Both PTAT and PLL films exhibit exponential growth but with the contact angle
      alternating between characteristic values. Ellipsometry and AFM show a gradual
      and complete disassembly of the PTAT but not the PLL films in a 24h period in the
      reducing environment in vitro. This study suggests a potential of using reducible
      LbL films for controlled DNA delivery.

PMID- 16962658
TI  - Development and mechanisms of fetal hypoxia in severe fetal growth restriction.
AB  - Severe fetal growth restriction (FGR) is often associated with hypoxia. We
      studied FGR hypoxia in an experimental model which is produced by exposing
      pregnant ewes to a hyperthermic environment. The study utilized simultaneous
      measurements of several relevant factors, e.g., uterine and umbilical blood flows
      and O(2) uptakes. Sixteen ewes were divided equally into control (C) and
      hyperthermic (HT) groups. Hyperthermia (40 degrees C for 12h/35 degrees C for
      12h; approximately 35% relative humidity, RH) was maintained for 80 days
      commencing at approximately 38 days gestational age (dGA term 147+/-3 days). All
      ewes were then placed in a control environment ( approximately 21 degrees C, 24h;
      approximately 30% RH) and studied at approximately 134 dGA. Mean HT placental and
      fetal weights were 39% and 45% of C, respectively (p<0.0001), umbilical O(2)
      uptake/kg fetus was 76% of C (p<0.01) and umbilical venous PO(2) was reduced
      (20.2 vs. 29.7 Torr, p<0.001). Contrary to the hypothesis that FGR hypoxia is due
      to maternal placental hypoperfusion, uterine flow was not reduced in relation to
      O(2) uptake. The uterine-umbilical venous PO(2) difference was enlarged (38 vs.
      23 Torr, p<0.0001). This difference is the expression of a balance between
      developmental changes in placental structure and oxidative metabolism, which have
      opposite effects in terms of fetal oxygenation. We postulate that FGR hypoxia
      results from disproportionate underdevelopment of those changes which allow for a
      progressive increase in umbilical O(2) uptake.

PMID- 16962660
TI  - The key to the gatekeepers: passive consent and other ethical issues surrounding
      the rights of children to speak on issues that concern them.

PMID- 16962659
TI  - Dynamic and static calcium gradients inside large snail (Helix aspersa) neurones
      detected with calcium-sensitive microelectrodes.
AB  - We have used quartz Ca2+-sensitive microelectrodes (CASMs) in large voltage
      clamped snail neurones to investigate the inward spread of Ca2+ after a brief
      depolarisation. Both steady state and [Ca2+]i transients changed with depth of
      penetration. When the CASM tip was within 20 microm of the far side of the cell
      the [Ca2+]i transient time to peak was 4.4+/-0.5s, rising to 14.7+/-0.7s at a
      distance of 80 microm. We estimate that the Ca2+ transients travelled
      centripetally at an average speed of 6 microm2 s(-1) and decreased in size by
      half over a distance of about 45 microm. Cyclopiazonic acid had little effect on
      the size and time to peak of Ca2+ transients but slowed their recovery
      significantly. This suggests that the endoplasmic reticulum curtails rather than
      reinforces the transients. Injecting the calcium buffer BAPTA made the Ca2+
      transients more uniform in size and increased their times to peak and rates of
      recovery near the membrane. We have developed a computational model for the
      transients, which includes diffusion, uptake and Ca2+ extrusion. Good fits were
      obtained with a rather large apparent diffusion coefficient of about 90+/-20
      microm2 s(-1). This may assist fast recovery by extrusion.

PMID- 16962661
TI  - Molecular characterization of two isoforms of defensin from hemocytes of the
      oyster Crassostrea gigas.
AB  - Antimicrobial peptides (AMPs) are important components of the host innate immune
      response against microbial invasion. We previously characterized the first AMP
      from an oyster, a defensin, that was shown to be continuously expressed in the
      mantle of Crassostrea gigas. In this study, we report the cDNA cloning of two new
      isoforms of the defensin AMP family (Cg-defh1 and Cg-defh2) from the hemocytes of
      the oyster. The deduced amino acid sequences reveal two peptides of 73 amino acid
      residues with a mature portion consisting of 43 amino acid residues. Cg-Defh1 and
      Cg-Defh2 share 86% amino acid identity and belong to the "arthropod-molluscs
      defensin family". qRT-PCR analyses indicate that Cg-defh2 is continuously
      expressed in the hemocytes of C. gigas. In addition, after a bacterial challenge,
      the level of Cg-defh2 transcripts decreases dramatically in the circulating
      hemocyte population and this decrease can be correlated with an increase of Cg
      defh2 transcripts in the gill and the mantle tissue, suggesting a possible
      migration of the hemocytes expressing Cg-defh2 towards the tissues implicated in
      the first defense barrier of the oyster. These results would suggest an important
      role of Cg-Defh2 in the oyster response to a microbial challenge.

PMID- 16962662
TI  - Fetal methylmercury exposure as measured by cord blood mercury concentrations in
      a mother-infant cohort in Hong Kong.
AB  - This study was designed to examine newborn infants in Hong Kong prenatally
      exposed to levels of methylmercury considered to increase risk of neurotoxic
      effects and to examine subject characteristics that modify the degree of prenatal
      mercury exposure. Mercury concentrations in 1057 sets of maternal and cord blood
      samples and 96 randomly selected maternal hair samples were measured. Subject
      characteristics were measured or collected by questionnaire. Of the 1057 cord
      blood samples collected only 21.6% had mercury concentrations less than 29 nmol/L
      (5.8 micro g/L). Median maternal hair mercury concentration was 1.7 ppm. The
      geometric mean cord to maternal blood mercury ratio was 1.79 to 1. Increasing
      maternal fish consumption and maternal age were found to be associated with
      increased cord blood mercury concentrations. Marine fish consumption increased
      cord blood mercury concentrations more than freshwater fish (5.09%/kg vs
      2.86%/kg). Female babies, maternal alcohol consumption and increasing maternal
      height were associated with decreased cord blood mercury concentrations. Pregnant
      women in Hong Kong consume large amounts of fish and as a result, most of their
      offspring have been prenatally exposed to moderately high levels of mercury. In
      this population, pregnant women should choose freshwater over marine fish and
      limit fish consumption.

PMID- 16962663
TI  - Neurobehavioral effects among inhabitants around mobile phone base stations.
AB  - BACKGROUND: There is a general concern on the possible hazardous health effects
      of exposure to radiofrequency electromagnetic radiations (RFR) emitted from
      mobile phone base station antennas on the human nervous system. AIM: To identify
      the possible neurobehavioral deficits among inhabitants living nearby mobile
      phone base stations. METHODS: A cross-sectional study was conducted on (85)
      inhabitants living nearby the first mobile phone station antenna in Menoufiya
      governorate, Egypt, 37 are living in a building under the station antenna while
      48 opposite the station. A control group (80) participants were matched with the
      exposed for age, sex, occupation and educational level. All participants
      completed a structured questionnaire containing: personal, educational and
      medical histories; general and neurological examinations; neurobehavioral test
      battery (NBTB) [involving tests for visuomotor speed, problem solving, attention
      and memory]; in addition to Eysenck personality questionnaire (EPQ). RESULTS: The
      prevalence of neuropsychiatric complaints as headache (23.5%), memory changes
      (28.2%), dizziness (18.8%), tremors (9.4%), depressive symptoms (21.7%), and
      sleep disturbance (23.5%) were significantly higher among exposed inhabitants
      than controls: (10%), (5%), (5%), (0%), (8.8%) and (10%), respectively (P<0.05).
      The NBTB indicated that the exposed inhabitants exhibited a significantly lower
      performance than controls in one of the tests of attention and short-term
      auditory memory [Paced Auditory Serial Addition Test (PASAT)]. Also, the
      inhabitants opposite the station exhibited a lower performance in the problem
      solving test (block design) than those under the station. All inhabitants
      exhibited a better performance in the two tests of visuomotor speed (Digit symbol
      and Trailmaking B) and one test of attention (Trailmaking A) than controls. The
      last available measures of RFR emitted from the first mobile phone base station
      antennas in Menoufiya governorate were less than the allowable standard level.
      CONCLUSIONS AND RECOMMENDATIONS: Inhabitants living nearby mobile phone base
      stations are at risk for developing neuropsychiatric problems and some changes in
      the performance of neurobehavioral functions either by facilitation or
      inhibition. So, revision of standard guidelines for public exposure to RER from
      mobile phone base station antennas and using of NBTB for regular assessment and
      early detection of biological effects among inhabitants around the stations are
      recommended.

PMID- 16962664
TI  - Eikenella corrodens in head and neck infections.
AB  - BACKGROUND: Eikenella corrodens (E. corrodens) is a Gram-negative facultative
      anaerobic bacillus that originally was thought to be an attenuated and indigenous
      bacterium. In recent years, a number of reports have documented that E. corrodens
      can be a potential pathogen not only in immunocompromised patients but also in
      hosts with normal immunity. We herein study E. corrodens infections of the head
      and neck encountered in our department. METHODS: Twenty-two consecutive patients
      treated in our department for E. corrodens infections of the head and neck were
      retrospectively analyzed. Microbial specimens were subjected to light microscopic
      examination, aerobic culture using chocolate and sheep blood agar media, and
      anaerobic culture using Brucella HK agar medium. Cultured bacteria were subjected
      to antimicrobial susceptibility tests by means of the broth microdilution method.
      RESULTS: There were 16 males and 6 females with an average age of 29.9 years. Two
      patients had malignancy, while the other patients had no particular risk factors
      or underlying diseases. Infected sites were the ear in 6 cases, pharynx in 12
      cases (tonsil in 10 cases), paranasal sinuses in 3 cases, and salivary gland in 1
      case. Seventeen patients suffered polymicrobial infections. Staphylococcus and
      Streptococcus were the most frequently detected pathogens coexisting with E.
      corrodens, and mixed infections of E. corrodens and Streptococcus milleri group
      bacteria were prone to form abscesses. Isolated E. corrodens was susceptible to
      third-generation cephems (MIC90 = 0.15-0.25 microg/ml), carbapenems (MIC90 < or =
      0.15 microg/ml), and new quinolones (MIC90 < or = 0.15 microg/ml), and resistant
      to oxacillin (MIC90 > 8 microg/ml), cefazolin (MIC90 > 4 microg/ml), macrolides
      (MIC90 = 4-8 microg/ml), and clindamycin (MIC90 > 4 microg/ml). CONCLUSIONS: E.
      corrodens infections of the head and neck occur most frequently in the tonsil
      even in hosts with normal immunity. Coexistence with Streptococcus milleri group
      bacteria and the use of ineffective antibiotics can be exacerbating factors.
      First-choice drugs for E. corrodens infections should be third-generation
      cephems, carbapenems, or new quinolones.

PMID- 16962665
TI  - A novel fluorescence-based cellular permeability assay.
AB  - Vascular permeability is a pathologic process in many disease states ranging from
      metastatic progression of malignancies to ischemia-reperfusion injury. In order
      to more precisely study tissue, and more specifically cell layer permeability,
      our goal was to create a fluorescence-based assay which could quantify
      permeability without radioactivity or electrical impedance measurements. Human
      aortic endothelial cells were grown in monolayer culture on Costar-Transwell
      clear polyester membrane 6-well cell culture inserts. After monolayer integrity
      was confirmed, vascular endothelial growth factor (VEGF(165)) at varying
      concentrations with a fixed concentration of yellow-green fluorescent 0.04 microm
      carboxylate-modified FluoSpheres microspheres were placed in the luminal chamber
      and incubated for 24 h. When stimulated with VEGF(165) at 20, 40, 80, and 100
      ng/ml, this assay system was able to detect increases in trans-layer flux of
      8.2+/-2.4%, 16.0+/-3.7%, 41.5+/-4.9%, and 58.6+/-10.1% for each concentration,
      respectively. This represents the first fluorescence-based permeability assay
      with the sensitivity to detect changes in the permeability of a cell layer to
      fluid flux independent of protein flux; as well as being simpler and safer than
      previous radioactive-and impedance-based permeability assays. With the
      application of this in vitro assay to a variety of pathologic conditions, both
      the dynamics and physiology relating to cellular permeability can be more fully
      investigated.

PMID- 16962666
TI  - Interventions with depressed mothers and their infants: modifying interactive
      behaviours.
AB  - BACKGROUND: Postpartum depression (PPD) has a prevalence ranging from 3% to 30%
      and is associated with serious infant growth and developmental problems.
      Interventions directed at improving maternal mood have been unsuccessful in
      producing changes in observed face-to-face interactions between mother and
      infant. The Keys to Caregiving (KTC) is an intervention program that helps
      parents to understand and respond to infant behaviours, with a goal of increasing
      positive affective expressions in infants. In this pilot study, KTC was used with
      mothers suffering from mild to moderate PPD and their infants. METHODS: PPD was
      confirmed by scores on the Edinburgh Postnatal Depression Scale and the Beck
      Depression Inventory. Eleven dyads completed the study. KTC was carried out in 5
      weekly group sessions, beginning at infant age of 3 months. Dyads were videotaped
      prior to and after KTC, using the Face-to-Face Still-Face paradigm, which
      assesses infants' responses during normal play and the effects of the Still-Face
      perturbation. The tapes were scored for infant facial emotion expressions.
      RESULTS: After intervention, infants displayed a marked increase in Interest and
      Joy when interacting face-to-face with their mothers, even though mothers'
      depression ratings did not change. LIMITATIONS: This pilot study is limited by
      lack of control dyads, however, it provides the foundation necessary for a full
      trial. CONCLUSIONS: This study suggests that intervention that focuses on what
      mothers do with their infants instead of how they feel can be effective in
      increasing infants' positive responsiveness and improving infant outcomes. Such
      interventions can be an essential component of treatment when mothers present
      with postpartum depression.

PMID- 16962667
TI  - A comparison of publication trends on avoidant personality disorder and social
      phobia.
AB  - The objective of this study was to ascertain the number of articles published per
      annum on the topics of avoidant personality disorder (APD) and social phobia (SP)
      in the period from 1973 to 2001. We hypothesized that while annual publication
      rates on SP would exhibit a sound growth, the number of scientific articles on
      APD published per annum would present a stagnant or declining trend. We performed
      a comprehensive literature review on APD and SP using the three largest existing
      databases for medical and psychological journals: MEDLINE, PsycINFO, and Web of
      Science. The references were gathered by means of the Reference Manager version
      9.5 software and transferred to an SPSS version 10 database for statistical
      analysis. The data were then input into regression models with the goal of
      predicting future growth of the scientific literature in these areas. The number
      of journal articles published annually on SP has steadily increased in the period
      from 1973 (1 article) to 2001 (118 articles). In contrast, the production of
      scientific literature on APD peaked in 1986 (5 articles) and subsequently
      declined. During the last decade reviewed, an average of fewer than two articles
      on APD was published per annum. Given the declining trend identified in this
      study, we believe that it is unlikely that the publication of scientific articles
      on APD will provide the empirical evidence required to validate this disorder in
      a foreseeable future. The permanence of APD on the rolls of the personality
      disorders should therefore be reassessed.

PMID- 16962668
TI  - The HSS3/4 enhancer of Crlz1-IgJ locus is another target of EBF in the pre-B cell
      stage of B cell development.
AB  - The HSS3/4 enhancer of Crlz1-IgJ locus was first characterized with regard to the
      activity of HSS1 IgJ promoter in the plasma cells, where both of HSS3/4 enhancer
      and HSS1 IgJ promoter were found to be opened simultaneously to drive the IgJ
      gene expression. Unexpectedly, the HSS3/4 enhancer was also found to be opened in
      the pre-B cells. However, this opening of HSS3/4 enhancer in the pre-B cells
      could not be related to the IgJ gene expression, because neither the IgJ promoter
      was opened nor its gene was expressed at the pre-B cell stage of B cell
      development. Instead, it was postulated that the opened HSS3/4 enhancer might act
      on some other nearby promoter in pre-B cells, which is now guessed to be the
      Crlz1 promoter located at 22.5 kb from it. In consistence with this pre-B cell
      specific opening of the HSS3/4 enhancer, a pre-B cell-specific in vivo footprint
      on a sequence similar to the EBF-binding consensus was detected within the
      enhancer. In this paper, we show that the protein causing the pre-B cell-specific
      in vivo footprint on a sequence similar to the EBF-binding consensus is truly EBF
      as judged by EMSA using various oligo-DNA competitors and anti-EBF antibodies.
      Also, as expected from other previous reports, EBF was shown to be expressed
      highly in pre-B cells, but very little or not in immature B, mature B and plasma
      cells using both the cell lines and FACS-sorted normal primary cells.
      Convincingly, mutations within the EBF site of HSS3/4 enhancer were shown to
      significantly impair the HSS3/4 enhancer activity in the pre-B cells, but not in
      the plasma cells.

PMID- 16962669
TI  - A novel accurate ACRS-PCR method with a digestion internal control for
      identification of wild type and YMDD mutants of hepatitis B virus strains.
AB  - As a consequence of the point mutation in the YMDD motif of the hepatitis B virus
      (HBV) polymerase gene, lamivudine-resistant mutants have been reported in chronic
      hepatitis B patients who underwent lamivudine therapy. The objective of the study
      was to develop a novel accurate artificially created restriction site (ACRS)
      method with a digestion internal control for identification of YMDD, YIDD and
      YVDD HBV strains. Three conserved, specific and diagnostic primers introducing
      NdeI, SspI and AleI cleavage sites were designed in order to identify YMDD, YIDD
      and YVDD strains, respectively; while, their reverse primers also modified with
      the above recognition sites in order to enzyme correctness monitoring and false
      outcome avoiding. Thirty-two chronic hepatitis B patients who had taken
      lamivudine for 1-3 years and checked by the Inno-LiPA HBV DR kit, were evaluated
      by the ACRS method and then compared to sequencing data. The results of the ACRS
      method revealed the YMDD mutant strain in 20 patients, YMDD plus YIDD pattern in
      1 patient, YMDD plus YVDD in 4 patients, the YIDD in 4 patients and mixed
      infection with each three strains in 1 patient. The sequencing and Inno-LiPA
      results were in agreement with the ACRS results. The novel ACRS method is a
      reliable, rapid and a cost-effective technique for determination of HBV strains
      with the wild type and YMDD mutant patterns.

PMID- 16962670
TI  - Identification of cell lines permissive for human coronavirus NL63.
AB  - Six cell lines routinely used in laboratories were tested for permissiveness to
      the infection with the newly identified human coronavirus NL63. Two monkey
      epithelial cell lines, LLC-MK2 and Vero-B4, showed a cytopathic effect (CPE) and
      clear viral replication, whereas no CPE or replication was observed in human lung
      fibroblasts MRC-5s. In Rhabdomyosarcoma cells, Madin-Darby-Canine-kidney cells
      and in an undefined monkey kidney cell line some replication was observed but
      massive exponential rise in virus yield lacked The results will lead to an
      improved routine diagnostic algorithm for the detection of the human coronavirus
      NL63.

PMID- 16962671
TI  - Nitric oxide-dependent changes in Schistosoma mansoni gene expression.

PMID- 16962672
TI  - Novel extended and branched N-terminal analogs of VIP.
AB  - The effects of vasoactive intestinal peptide (VIP) are primarily mediated through
      VPAC1 and VPAC2, receptors that are preferentially coupled to adenylate cyclase
      activation. As a large majority of the potent VIP antagonists have modifications
      in the N-terminal domain of the peptide, the effect of multiplication of this
      domain on VIP was examined with the aim of possibly amplifying peptide-receptor
      (VPAC1) activation. Several VIP analogs were designed and synthesized, each
      carrying multiplication of the N-terminal domain that was obtained by either
      linear tandem extension or by parallel branching. Circular dichorism (CD)
      analysis revealed that these extended/branched peptides maintained an alpha
      helical structure in organic environment, similar to VIP. A specific branched VIP
      analog was found to be slightly more potent towards VPAC1-related cAMP production
      as compared to VIP. This analog could have potential therapeutic value in several
      disorders, similar to VIP. Two branched N-terminal VIP sequences demonstrated
      superior receptor binding and activation as compared to two N-terminals in
      tandem. The results suggest that correct alignment of the VIP N-terminal region
      is important for receptor binding and activation. However, increased receptor
      binding was not directly associated with increased cAMP production suggesting
      steric dynamic interactions.

PMID- 16962673
TI  - The C-terminal CD47/IAP-binding domain of thrombospondin-1 prevents camptothecin-
      and doxorubicin-induced apoptosis in human thyroid carcinoma cells.
AB  - Camptothecin and doxorubicin belong to a family of anticancer drugs that exert
      cytotoxic effects by triggering apoptosis in various cell types. However there
      have only been few investigations showing that matricellular proteins like
      thrombospondin-1 (TSP-1) could be involved in the underlying mechanism of this
      cytotoxicity. In this report, using Hoechst reagent staining, reactive oxygen
      species production and caspase-3 activity measurement, we determined that both
      camptothecin and doxorubicin induced apoptosis in human thyroid carcinoma cells
      (FTC-133). On the one hand, we demonstrated that camptothecin and doxorubicin
      inhibited TSP-1 expression mainly occurring at the transcriptional level. On the
      other hand, drug-induced apoptosis determined by western blot analysis for PARP
      cleavage and caspase-3 activity measurement, was significantly decreased in
      presence of exogenous TSP-1. In order to identify the sequence responsible for
      this effect, we used the CD47/IAP-binding peptide 4N1 (RFYVVMWK), derived from
      the C-terminal domain of TSP-1, and known to play a role in apoptosis. Thus, in
      presence of 4N1, camptothecin and doxorubicin-induced pro-apoptotic activity was
      considerably inhibited. These findings suggest that induction of apoptosis by
      camptothecin or doxorubicin in FTC-133 cells is greatly dependent by a down
      regulation of TSP-1 expression and shed new light on a possible role for TSP-1 in
      drug resistance.

PMID- 16962674
TI  - Septal pacing preserving better left ventricular mechanical performance and
      contractile synchronism than apical pacing in patients implanted with an
      atrioventricular sequential dual chamber pacemaker.
AB  - BACKGROUND: Permanent pacing is the treatment for chronotropically incompetent
      hearts. However, the right ventricular (RV) apical pacing-induced asynchrony,
      even maintaining the atrioventricular (AV) sequential activation, has depressed
      left ventricular contractility. Whether RV septal pacing would less compromise
      the electromechanical performance of the left ventricle and the chronotropic
      effect on myocardial contractility, is unknown. METHODS: We prospectively studied
      42 patients without structural heart diseases and with symptomatic bradycardia.
      There were 10 patients receiving atrial pacing (AAI) pacemakers, 18 patients
      having AV sequential pacing at RV apex (DDDapx) and 14 patients being AV
      sequentially paced at septum (DDDspt). Echocardiography was performed before and
      within 72 h after the pacemaker implantation. The ventricular mechanical
      performance and asynchrony was compared in conditions of programmed rates of 60,
      80 and 100/min. RESULTS: Myocardial performance index was significantly better in
      DDDspt than in DDDapx patients (p=0.003). With faster programmed rate, the QRS/RR
      increased (p<0.05) in DDDapx patients with more inter- and intraventricular
      asynchrony, implicating the disadvantage of prolonged depolarization time. The
      DDDspt group demonstrated comparable parameters of diastolic function to AAI
      patients and preserved mechanical performance during accelerated pacing.
      CONCLUSIONS: RV septal pacing showed the advantages of shorter depolarization
      time, less ventricular contractile asynchrony, better mechanical performance and
      preserved chronotropic response on myocardial contractility in comparison with
      apical pacing.

PMID- 16962675
TI  - Dosimetric comparison of stereotactic body radiotherapy in different respiration
      conditions: a modeling study.
AB  - PURPOSE: To evaluate the dosimetric consequences for irradiated lung tissue for
      different respiration conditions for hypofractionated stereotactic body
      radiotherapy (SBRT). METHODS AND MATERIALS: Thirteen patients with lung lesion
      undergoing SBRT treatment in shallow breathing with abdominal compression (SB+AP)
      underwent additional multislice CT studies in free breathing (FB), deep
      inspiration and expiration breath hold (DIBH, DEBH). For each patient 6 different
      treatment plans were designed for the various respiration conditions applying
      standard (7/7/10 mm), reduced (5/5/5 mm) and individual margins. The FB plan with
      standard margins was used as a reference. The percentage of volume of the
      ipsilateral lung receiving total doses > or=12, 15> or= and > or=18 Gy, mean lung
      dose (D(mean)), NTCP corrected for fractionation effects and the total monitor
      units (MU) were evaluated. RESULTS: With DIBH it was possible to reduce all lung
      dose parameters by about 20%. Applying reduced margins in DIBH, this reduction
      was even increased to about 40%. The standard technique (SB+AP) with individual
      margins showed similar results as DIBH with standard margins. DEBH showed some
      improvement over FB only when reduced margins were applied. Only for 5/13
      patients NTCP values >1% were obtained. For these patients a significant NTCP
      reduction was achieved with DIBH techniques. CONCLUSIONS: In SBRT shallow
      breathing with abdominal compression produces acceptable results concerning lung
      DVHs. DIBH, especially with reduced margins, showed the best lung sparing. For
      the clinical implementation of such a technique some form of gating is advisable.
      However, there are some practical limitations due to high fractional doses.

PMID- 16962676
TI  - Dosimetric verification of 6 and 18 MV intensity modulated photon beams using a
      dedicated fluoroscopic electronic portal imaging device (EPID).
AB  - BACKGROUND AND PURPOSE: Intensity modulated radiation therapy offers a dose
      distribution improvement by modulating the two-dimensional X-ray fluence. This
      increases the treatment complexity from the planning phase to the verification
      one. Pre-treatment dosimetric verifications of each treatment field are strictly
      necessary, films and EPIDs are generally used for this purpose. In this paper we
      investigated the dosimetric characteristics of a commercially available
      fluoroscopic EPID "I'mRT QA" (Scanditronix-Wellhofer) (I-QA) based on charge
      coupled device camera (CCD) and we present a new method for optimising the EPID's
      response. MATERIALS AND METHODS: I-QA is an optically sealed EPID and it is
      designed for on-line two-dimensional measurements of relative dose distribution.
      Dose profiles measured in water with diodes and dose distributions measured in
      water-equivalent phantoms with films were compared with those obtained with the I
      QA for homogeneous and intensity modulated 6 and 18 MV photon beams. RESULTS AND
      CONCLUSIONS: I-QA measurements depend on the field size and on the two
      dimensional energy spectrum of the beam. The incoming beam was modified
      positioning a series of lead and plastic (RW3) slabs above the fluorescent screen
      to obtain a homogeneous response of the I-QA over the whole sensitive area. The
      thickness of lead and RW3 sheets was optimised to get the best matching between
      diodes, films and the I-QA measurements for each energy. Gamma index evaluations
      showed a correspondence between I-QA measurements and diode ones within 3% or 2
      mm for homogeneous and simple modulated fields, and within 5% or 3mm for complex
      modulated fields.

PMID- 16962677
TI  - Contralateral breast doses following radiotherapy of the breast and regional
      lymph nodes: Measurements and treatment planning calculations.
AB  - PURPOSE: To measure the dose distribution in the contralateral breast (CB)
      following radiotherapy of the breast and regional lymph nodes by a 4-field
      technique, and to examine whether related treatment planning calculations of CB
      doses reproduce the measurements. MATERIALS AND METHODS: CB doses were measured
      by thermoluminescence dosimetry on the surface of 8 patients and in an
      anthropomorphic phantom. Dose calculations at corresponding points of interest
      were performed by the treatment planning system Helax-TMS 6.1 using the pencil
      beam or the collapsed cone algorithm. RESULTS: The measured CB doses were
      typically between 1% and 15% of the prescribed dose. The dose decreased
      significantly both in the medial-lateral and cranial-caudal direction. The
      average ratio of the measured to the calculated CB dose was about 0.7 and 0.9 for
      the pencil beam and the collapsed cone algorithm, respectively. One of the
      treatment fields aimed at the regional lymph nodes and some of the chest wall
      gave the highest contribution to the CB dose. CONCLUSIONS: The dose distribution
      in the CB following locoregional radiotherapy of the breast and regional lymph
      nodes is quite inhomogeneous. The collapsed cone algorithm may be used for
      estimating doses to the CB. Some concern is raised regarding the current field
      arrangement and the consequences for the CB dose.

PMID- 16962678
TI  - Involvement of medullary GABAergic and serotonergic raphe neurons in respiratory
      control: electrophysiological and immunohistochemical studies in rats.
AB  - In the present study we first examined the possible involvement of the putative
      neurotransmitters gamma-aminobutyric acid (GABA) and serotonin (5-HT) in raphe
      induced facilitatory or inhibitory effects on the respiratory activity of rats.
      Secondly, we investigated the possibility of spinal projections of GABAergic and
      serotonergic neurons from the medullary raphe nuclei to the phrenic motor nucleus
      (PMN). We observed that an intravenous (i.v.) injection of (+)-bicuculline, a
      GABA(A) receptor antagonist, significantly reduced respiratory inhibition induced
      by electrical stimulation of the raphe magnus (RM) or the raphe obscurus (RO). On
      the other hand, an i.v. injection of methysergide, a broad-spectrum 5-HT receptor
      antagonist, significantly reduced the respiratory facilitation induced by
      electrical stimulation of the raphe pallidus (RP) or RO. By using a combined
      method of retrograde tracing with Texas Red injected into the PMN region at
      segments C4 and C5 and immunohistochemical labeling, we observed that glutamic
      acid decarboxylase (GAD; a GABA synthesizing enzyme) immunopositive and Texas Red
      double labeled neurons were predominantly localized in the RM, and additionally
      in the RO. However 5-HT immunopositive and Texas Red double-labeled neurons were
      predominantly localized in the RP, and additionally in the RO and RM. These
      findings suggest that RM-, or RO-induced inhibitory effects, are transmitted, at
      least in part, to the PMN via a direct GABAergic descending pathway. The RP-, or
      RO-induced facilitatory effects in rats however, are transmitted via a
      serotonergic descending pathway.

PMID- 16962679
TI  - Open-loop control of the biomass concentration within the growth phase of
      recombinant protein production processes.
AB  - Recombinant protein production processes are typically divided into two phases.
      In the first one, pure cell propagation takes place, while in the second one
      product formation is switched on within the cells by adding an inducer. In the
      initial biomass formation phase, the cell density is rather low and, hence, the
      measurement quantities that could be used to determine the process' state depict
      small values and are rather severely distorted by measurement noise. Because of
      these measurement problems, the fermentation cannot be reliably controlled by
      feedback control during this first production phase; instead, the process must be
      controlled in an open-loop fashion. The consequence, worked out in this paper, is
      to design substrate feed rate profiles for the growth phase in such a way that
      they are robust with respect to the main disturbances observed in practice. The
      robustness of the biomass formation is shown to be primarily dependent on the
      specific growth rate adjusted in the first hours. High batch-to-batch
      reproducibility can be obtained with exponential feeding profiles F(t)
      corresponding to specific growth rates micro(set) well below the maximal specific
      growth rate micro(max) of the organism. The reduction in the growth rate needed
      to obtain a robust process behavior depends on the inaccuracies in the initial
      biomass concentrations. Quantitative feed rate profiles were obtained by
      numerical simulation and these results were validated experimentally by means of
      a series of cultivation runs, where a recombinant pharmaceutical protein was
      produced. All experimental data confirmed the assumptions made in the robust
      process design study.

PMID- 16962680
TI  - Histaminase PEGylation: preparation and characterization of a new bioconjugate
      for therapeutic application.
AB  - Copper amine oxidase catalyses the oxidative deamination of primary amino groups
      of several biogenic amines, one of which is histamine, the principal chemical
      mediator of the first phase of allergic reactions. Looking forward to a possible
      future therapeutic application of this enzyme in the field of histamine-mediated
      afflictions, we developed a simple method for the purification of a histaminase
      from grass pea shoots, a source particularly enriched with the enzyme.
      Furthermore, in order to improve its therapeutic potential, in particular to
      reduce the high impurity due to its heterologous source, we conjugated the
      protein with poly(ethylene glycol) and tested the molecular, immunogenic and
      pharmacokinetic properties of the native and modified forms. The PEGylated enzyme
      showed molecular and enzymatic properties similar to those of the unmodified one,
      but the PEGylation extended the permanence of the injected drug in the body and
      eliminated its high immunogenic behaviour. The considerable ease of native
      histaminase production as well as the improved properties after PEGylation, make
      this engineered plant enzyme a suitable drug candidate for alternative treatment
      of histamine-mediated affections.

PMID- 16962681
TI  - Clinical and electrophysiological correlations in type 2 diabetes mellitus at
      diagnosis.
AB  - The purpose of this study was to evaluate, in newly diagnosed type 2 diabetes
      mellitus (DM): (1) the prevalence and staging of peripheral neuropathy, as well
      as its possible relationship with metabolic profile; (2) the clinical value of
      both the Diabetic Neuropathy Index (DNI) and the Diabetic Neuropathy Score (DNS),
      and their reciprocal concordance, as a screening method for neuropathy. Thirty
      nine newly diagnosed DM subjects underwent: neurological examination, nerve
      conduction studies (NCS), quantitative sensory system and cardiovascular
      autonomic function assessments. Peripheral neuropathy was observed in 72% of the
      subjects (its staging was similar to that of patients with longer disease
      history), while another 10% of them showed a borderline neuropathy. The Deep
      Breathing test was abnormal in 28% of the patients; postural hypotension was
      found in 6%. The same proportion (82%) of subjects who scored positively on the
      DNI showed altered NCS, while the quantitative sensory system assessments had a
      low sensitivity in order to detect the neuropathy. No correlation was found
      between metabolic indexes and DNI/DNS parameters. The high prevalence of
      peripheral and autonomic function alterations suggests that each newly diagnosed
      diabetic subject should be screened for neuropathy by the DNI, to reduce the
      negative prognostic influence of this complication.

PMID- 16962683
TI  - Hypothalamic clamp on insulin release by leptin-transgene expression.
AB  - The effects of sustained leptin action locally in the hypothalamus on the
      functional link between fat accrual and insulin secretion after chronic high fat
      diet (HFD) consumption in leptin-deficient ob/ob mice, and on the post-prandial
      insulin response in rats consuming regular chow diet (RCD), was examined in this
      study. A single intracerebroventricular (icv) injection of recombinant adeno
      associated virus vector encoding leptin gene (rAAV-lep) enhanced hypothalamic
      leptin-transgene expression in ob/ob mice consuming RCD and suppressed the time
      related weight gain and fat accumulation concomitant with abrogation of
      hyperinsulinemia and enhanced glucose tolerance. This increased hypothalamic
      leptin-transgene expression continued to impose insulinopenia and increased
      glucose tolerance but was ineffective in suppressing weight gain and fat
      accumulation after these mice were switched to chronic HFD consumption. A similar
      icv rAAV-lep pretreatment in rats consuming RCD markedly attenuated the post
      prandial rise in insulin release concomitant with suppressed weight and fat
      depots. These results show for the first time that a sustained hypothalamic
      leptin action can stably clamp pancreatic insulin secretion independent of the
      status of fat accrual engendered by diets of varying caloric enrichment. Thus,
      the efficacy of increased leptin afferent signaling in the hypothalamus to
      persistently restrain pancreatic insulin release and insulin resistance can be
      explored as an adjunct therapeutic modality to alleviate pathophysiological
      derrangements that confer type 2 diabetes.

PMID- 16962684
TI  - APP mRNA splicing is upregulated in the brain of biglycan transgenic mice.
AB  - Many of the risk factors for cerebrovascular disease and atherosclerosis also
      increase the risk of Alzheimer's disease, characterized by the cerebral
      deposition of beta-amyloid plaques resulting from the abnormal processing of the
      transmembrane amyloid precursor protein (APP). The initiating event of
      cholesterol-induced atherosclerosis is the retention and accumulation of
      atherogenic apolipoprotein B (apoB) together with low-density lipoproteins in the
      vascular intima. Biglycan, a member of the small leucine-rich protein family, was
      suspected of contributing to this process. The individual and combined
      overexpressions of biglycan and apoB-100 were therefore examined on the cortical
      APP mRNA levels of transgenic mice by means of semiquantitative PCR. As compared
      with the control littermates, transgenic biglycan mice had significantly
      increased cortical APP695 (122%) and APP770 (157%) mRNA levels, while the double
      transgenic (apoB(+/-)xbiglycan(+/-)) mice did not exhibit any changes. These
      results provide the first experimental evidence that the atherogenic risk factor
      biglycan alters APP splicing and may participate in the pathogenesis of both
      Alzheimer and vascular dementias.

PMID- 16962685
TI  - Immunoreactivity enhancement with chelators for increasing the detection
      sensitivity of human PrPSc by Western blotting.
AB  - Prion diseases are neurodegenerative disorders affecting humans as Creutzfeldt
      Jakob disease. The host-encoded prion protein (PrP(C)) will be converted into a
      structurally altered isoform (PrP(Sc)). PrP(Sc) differ in sizes and glycoform
      patterns and can be identified using molecular typing with Western blotting. The
      electrophoretic mobility of PrP(Sc) changes on treatment with metal ions or
      chelators prior to digestion with proteases. The effects of chelators applied to
      PrP(Sc) after protease digestion had not been examined in detail, we investigated
      these effects in this study. Application of EDTA, NTA and DTPA, and to a lesser
      extent EGTA, significantly enhanced PrP(Sc) signals in immunoblots. PrP(Sc)
      intensities increased two- to three-fold compared with untreated PrP(Sc). Since
      the immunoblot method is highly specific, sensitivity is the limiting factor.
      Enhancing sensitivity might be important in the determination of PrP(Sc) at
      levels close to or just below the limits of detection. It is to be expected that
      application of chelators to digested protein samples will increase the
      sensitivity of PrP(Sc) detection using the Western blot technique.

PMID- 16962686
TI  - A rat model of Parkinsonism shows depletion of dopamine in the retina.
AB  - The retinal dopamine (DA) deficiency is an important feature of the pathogenesis
      in Parkinson's disease (PD) visual dysfunction. Systemic inhibition of complex I
      (rotenone) in rats has been proposed as a model of PD. In this study, we
      investigated whether systemic inhibition of complex I can induce impairment of DA
      ergic cells in the retina, similar to the destruction of retinal cells found in
      PD patients. Rotenone (2.5mg/kg i.p., daily) was administered over 60 days.
      Neurochemically, rotenone treated rats showed a depletion of DA in the striatum
      and substantia nigra (SN). In addition, the number of retinal DA-ergic amacrine
      cells was significantly reduced in the rotenone treated animals. This study is
      the first one giving highlight towards a deeper understanding of systemic complex
      I inhibition (rotenone as an environmental toxin) and the connection between
      both, DA-ergic degeneration in the nigrostriatal pathway, and in the DA-ergic
      amacrine cells of the retina.

PMID- 16962688
TI  - Can an interview score sheet assist with student selection onto the bachelor of
      science/diploma of higher education (adult) nursing programme? Findings from a
      pilot study.
AB  - AIM: To develop an interview score sheet (ISS) to assist with the selection of
      student nurses on the Bachelor of Science (B.Sc.)/Diploma of Higher Education
      (DipHE) (Adult). METHOD: A pilot study was undertaken over a 6-month period to
      design and used a questionnaire to collect information on the candidate at
      interview. This questionnaire was called the "interview score sheet" (ISS). Using
      the ISS, each candidate was scored independently by two interviewers. MAIN
      OUTCOME MEASURES: The study was used to evaluate the usefulness of a score sheet
      at interview in aiding with the selection of candidates. Also the study was used
      to identify the demographics of the candidates and to assess the consistency of
      the scoring system. RESULTS: One hundred and twenty six candidates, ageing from
      16 to 51 years were interviewed over 6 months. Ninety of the candidates were
      accepted onto the course. The highest score achievable on the ISS was 40, and the
      lowest was 2. Of those candidates accepted (n=90) the average score was 28, and
      for those candidates rejected (n=36) the average score was 20.6. CONCLUSION: The
      ISS proved to be a useful tool to decide on candidate suitability. Those
      candidates accepted onto the course were more likely to be scored higher than
      those rejected. FUTURE STUDY: Correlation of scores with firstly the
      characteristics of the successful candidates, and secondly with the
      characteristics of those who did not complete the 3-year programme.

PMID- 16962689
TI  - Pertussis vaccine and infantile spasms.
AB  - The boy (case 1) at the age of 12 weeks started having attacks and jercked after
      the first injection of triple vaccine (diphtheria, retanus and whole cell
      pertussis) The electro-encephalogram (EEG) confirmed the typical features of
      hypsarrhythmia. Intramuscular ACTH was commenced for 2 weeks. No problem was
      reported until the age of 9 years when he started having attacks of jercking. He
      was treated with sodium valproate. The boy of the second case was a first cousin
      of case 1. At the age of 11 years the boy had momentary black outs. The EEG
      showed findings of idiopathic epilepsy. Treatment with sodium valproate was
      commenced. The children of both cases belong to a family in which there is a
      trendency to seizures. It seems unlikely the triple vaccine produced the
      infantile spasms in case 1.

PMID- 16962690
TI  - Therapeutic efficacy of vesicular stomatitis virus-based E6 vaccination in
      rabbits.
AB  - Millions of people worldwide are currently infected with human papillomaviruses
      (HPVs). A therapeutic HPV vaccine would have widespread applicability because HPV
      associated lesions are difficult to treat and may progress to carcinoma. We
      developed three attenuated VSV recombinants expressing the cottontail rabbit
      papillomavirus (CRPV) early protein E6 for use as vaccines. In cultured cells,
      two vectors expressed different levels of the E6 protein, and one expressed a
      ubiquitin-E6 fusion protein. All three were tested for therapeutic efficacy in
      the cottontail rabbit papillomavirus (CRPV)-rabbit model. Mock vaccination had no
      effect on papilloma growth. In contrast, inoculation with any of the VSV-E6
      vaccines reduced the rate of papilloma growth to as little as 24% the rate in the
      controls. In five experiments, these effects were achieved after a single
      immunization. Furthermore, complete papilloma regression occurred in some rabbits
      observed for 4 months. A VSV-based papillomavirus E6 vaccine could have
      significant advantages over other therapeutic HPV vaccine candidates described to
      date.

PMID- 16962691
TI  - Superficial acral fibromyxoma of the distal phalanx of the thumb.
AB  - Superficial acral fibromyxoma is an uncommon benign tumour which was first
      described recently (Fetsch et al., 2001, Human Pathology 32: 704-714). It has
      been reported several times since, suggesting it is more common than initially
      thought.

PMID- 16962692
TI  - A one-stage shoulder arthrodesis and Brooks Seddon pectoralis major to biceps
      tendon transfer for upper brachial plexus injuries.
AB  - Reconstructive procedures to optimise the function of patients with upper
      brachial plexus injuries are well described. From 1999 to 2005, nine patients
      underwent a single stage Brooks Seddon pectoralis major to biceps tendon transfer
      with a glenohumeral arthrodesis for restoration of elbow flexion and shoulder
      stability. All of these patients had sustained traumatic upper trunk brachial
      plexus injuries which had not responded to nerve repair, grafting or
      neurotisation or had a delayed presentation. Results were assessed using a
      goniometer and the Medical Research Council strength grading. At follow-up of
      28.5 months, the average arc of elbow flexion was 103 degrees and eight had good
      elbow flexion power. There was one failure. We had two complications, both
      related to humerus fractures below the arthrodesis plate. Both united with
      conservative treatment. Our experience has given encouraging results with a high
      level of patient satisfaction. Our indications, operative technique and results
      are presented.

PMID- 16962693
TI  - Women's status and child well-being: a state-level analysis.
AB  - We conducted an ecologic analysis of the relation between women's status and
      child well-being in the 50 United States. State-level women's status was assessed
      via four composite indices: women's political participation, economic autonomy,
      employment and earnings, and reproductive rights. Child well-being was measured
      via five outcomes: percentage of low birthweight babies, infant mortality, teen
      mortality, high school dropout rate, and teen birth rate. Higher state-level
      women's status on all indicators was associated with significantly better state
      level child well-being in unadjusted analyses. Several associations remained
      significant after adjusting for income inequality and state racial composition.
      Women's political participation was associated with a significantly lower
      percentage of low birthweight babies (p<.001) and lower teen birth rates (p<.05).
      Women's employment and earnings was associated with lower infant mortality
      (p<.05) and teen birth rates (p<.05). More economic and social autonomy for women
      was associated with better child outcomes on all measures (p<.01 all). Greater
      reproductive rights were associated with significantly lower infant mortality
      (p<.01). We conclude that child well-being is worse in states where women have
      lower political, economic, and social status. Women's status is an important
      aspect of children's social context which may impact their well-being. Multi
      level analyses of the association between state-level women's status and child
      well-being are needed.

PMID- 16962694
TI  - From rhetoric to reality: A systemic approach to understanding the constraints
      faced by Health For All initiatives in England.
AB  - The increased appreciation of the effects socio-ecological factors have on
      health, witnessed over the last few decades, has given rise to many
      international, national, and local Health For All (HFA) initiatives tasked with
      addressing them. However, such initiatives have had to operate within
      environments which were not specifically designed for them or for the new social
      (rather than medical) perspective on health they were based upon. As a result,
      they have been facing significant barriers and constraints to fulfilling their
      mission. This paper explores the constraints which are imposed on such
      initiatives by the various environments within which they are nested. Drawing
      upon our experience in evaluating European Healthy City (HC) projects and English
      Health Action Zones (HAZs), we develop a dynamic conceptual model which shows how
      the national, governmental policy, interorganisational, organisational, and
      initiative environments relate with each other and their cumulative effects on
      initiatives. We argue that this model, and the principles on which it is based,
      can be used constructively to identify constraints facing HFA-type initiatives in
      many countries. We use our case study of English HCs and HAZs to illustrate the
      applicability of the model in a particular national context. We, first, interpret
      the model to reflect differences and similarities between their respective
      environments and trace the sources of the different constraints they encountered.
      We, then, show how an alternative structural configuration could enable some of
      these constraints to be eliminated. We argue that what is needed for HFA
      initiatives to be able to fulfill their brief in full is for governments to
      rethink existing organisational structures and update them to match the evolution
      of ideas on health which have emerged over the last decades.

PMID- 16962695
TI  - Decentred comparative research: Context sensitive analysis of maternal health
      care.
AB  - Cross-national comparison is an important tool for health care research, but too
      often those who use this method fail to consider important inter-national
      differences in the social organisation of health care and in the relationship
      between health care practices and social experience. In this article we make the
      case for a context-sensitive and reflexive analysis of health care that allows
      researchers to understand the important ways that health care systems and
      practices are situated in time and place. Our approach--decentred comparative
      research--addresses the often unacknowledged ethnocentrism of traditional
      comparative research. Decentred cross-national research is a method that draws on
      the socially situated and distributed expertise of an international research team
      to develop key concepts and research questions. We used the decentred method to
      fashion a multilevel framework that used the meso level of organisation (i.e.,
      health care organisations, professional groups and other concrete organisations)
      as an analytical starting point in our international study of maternity care in
      eight countries. Our method departs from traditional comparative health systems
      research that is most often conducted at the macro level. Our approach will help
      researchers develop new and socially robust knowledge about health care.

PMID- 16962696
TI  - Protective effect of quercetin on experimental chronic cadmium nephrotoxicity in
      rats is based on its antioxidant properties.
AB  - Oxidative stress can play a key role in Cd-induced dysfunctions. Quercetin is a
      potent oxygen free radicals scavenger and a metal chelator. Our aim was to study
      the effect of quercetin on Cd-induced kidney damage and oxidative stress as well
      as its mechanism of action. Wistar rats were distributed in four experimental
      groups: control rats; Cd; quercetin and Cd+quercetin. Renal toxicity was
      evaluated by measuring urinary excretion of proteins, albumin, glucose and
      enzymes markers of tubular necrosis, as well as plasma concentration of
      creatinine. Plasma TBARS concentration and activity of antioxidant enzymes in
      kidney were also measured. Renal cell damage was assessed by electron microscopy.
      Animals that received both Cd and quercetin showed a better renal function than
      those receiving Cd alone. Cd-induced tubular lesions were markedly reduced in
      rats that also received quercetin. Cd-induced increase in plasma TBARS was
      prevented by the administration of quercetin. Total plasma antioxidants and renal
      superoxide dismutase and glutathione-reductase activities were higher in the
      group that received Cd and quercetin than in rats that received Cd alone.
      Quercetin administration does not modify the renal content or the urinary
      excretion of Cd. In conclusion, quercetin treatment prevents renal tubular damage
      and increased oxidative stress induced by chronic Cd administration, most
      probably throughout its antioxidant properties.

PMID- 16962697
TI  - Crystal structure of thrombin in complex with fibrinogen gamma' peptide.
AB  - Elevated levels of heterodimeric gamma(A)/gamma' fibrinogen 2 have been
      associated with an increased incidence of coronary artery disease, whereas a
      lowered content of gamma' chains is associated with an increased risk of venous
      thrombosis. Both situations may be related to the unique features of thrombin
      binding to variant gamma' chains. The gamma' peptide is an anionic fragment that
      binds thrombin with high affinity without interfering directly with substrate
      binding. Here we report the crystal structure of thrombin bound to the gamma'
      peptide, solved at 2.4 A resolution. The complex reveals extensive interactions
      between thrombin and the gamma' peptide mediated by electrostatic contacts with
      residues of exosite II and hydrophobic interactions with a pocket in close
      proximity to the Na(+) binding site. In its binding mode, the gamma' peptide
      completely overlaps with heparin bound to exosite II. These findings are
      consistent with functional data and broaden our understanding of how thrombin
      interacts with fibrinogen at the molecular level.

PMID- 16962698
TI  - Conformations of adducts formed between the genotoxic benzo[a]pyrene-7,8-dione
      and nucleosides studied by density functional theory.
AB  - Benzo[a]pyrene (BP) is a widely distributed environmental pollutant that is
      metabolized by mammalian cells to a variety of genotoxic and carcinogenic
      intermediates that form covalent adducts with cellular DNA. One such pathway
      involves the metabolic activation of BP by members of the aldo-keto-reductase
      (AKR) family of enzymes to the highly reactive ortho-quinone, benzo[a]pyrene-7,8
      dione (BPQ). This compound has been reported to react with the 2'
      deoxynucleosides, dA and dG, under physiological conditions. Four BPQ-dG adducts
      and two -dA adducts were identified by mass spectrometry and NMR methods [Balu et
      al. (2004) Chem. Res. Toxicol. 17, 827-838]. However, the detailed conformations
      and absolute configurations around the linkage site have not been resolved. In
      order to determine the full conformations of these purine adducts, we carried out
      quantum mechanical geometry optimization using density functional theory. In the
      case of the BPQ-guanine adducts, six possible structures, each of which consists
      of two isomers, were identified. However, in the case of the adenine adducts,
      only four isomers were identified. The results suggest that stereoisomeric adduct
      pairs are expected to adopt opposite orientations with respect to the 5'-->3'
      direction of the modified DNA strands. The stereochemistry-dependent variations
      in adduct orientation may produce different biological effects, as has been
      observed in the case of DNA adducts derived from other metabolites of polycyclic
      aromatic hydrocarbons.

PMID- 16962699
TI  - Interaction energy decomposition in protein-protein association: a quantum
      mechanical study of barnase-barstar complex.
AB  - Protein-protein interactions are very important in the function of a cell.
      Computational studies of these interactions have been of interest, but often they
      have utilized classical modelling techniques. In recent years, quantum mechanical
      (QM) treatment of entire proteins has emerged as a powerful approach to study
      biomolecular systems. Herein, we apply a semi-empirical divide and conquer (DC)
      methodology coupled with a dielectric continuum model for the solvent, to explore
      the contribution of electrostatics, polarization and charge transfer to the
      interaction energy between barnase and barstar in their complex form. Molecular
      dynamic (MD) simulation was performed to account for the dynamic behavior of the
      complex. The results show that electrostatics, charge transfer and polarization
      favor the formation of the complex. Our study shows that electrostatics dominates
      the interaction between barnase and barstar ( approximately 73%), while charge
      transfer and polarization are approximately 21% and approximately 6%,
      respectively. Close inspection of the polarization and charge-transfer effects on
      the charge distribution of the complex reveals the existence of two, well
      localized, regions in barstar. The first region includes the residues between P27
      and Y47 and the second region is between N65 and D83. Since no such regions could
      be detected in barnase clearly suggests that barstar is well optimized for
      efficiently binding barnase. Furthermore, using our interaction energy
      decomposition scheme, we were able to identify all residues that have been
      experimentally determined to be important for the complex formation and to
      suggest other residues never have been investigated. This suggests that our
      approach will be useful as an aid in further understanding protein-protein
      contacts for the ultimate goal to produce successful inhibitors for protein
      complexes.

PMID- 16962700
TI  - Photochemical probing of the B--a conformational transition in a linearized pUC19
      DNA and its polylinker region.
AB  - We induced the B-to-A conformational transition by ethanol in a linearized pUC19
      DNA. A primer extension method was used in combination with UV light irradiation
      to follow the transition, based on pausing of DNA synthesis due to the presence
      of damaged bases in the template. Primer extension data highly correlated with
      the results of another method monitoring the B-A transition, i.e. inhibition of
      restriction endonuclease cleavage of UV light-irradiated DNA. Primer extension
      enabled us to locate damaged nucleotides within the region of interest. Most
      damaged nucleotides were located in B-form trimers, exclusively containing both
      pyrimidine bases (TTC, TCT, CTC, and CTT), and in a cytosine tetramer. The amount
      of damaged bases decreased in the course of B-A transition. Some of the damage
      even disappeared in the A-form, which mainly concerns the C(4) and C(3) blocks.
      The cleavage was nearly restored in the A-form within this region (Eco88I). On
      the contrary the decrease of damage was less significant with thymine dimers,
      only dropping to 50-60% of the B-form level. Consequently, the cleavage with
      EcoRI and HindIII remained mostly as before the transition (75% and 60% of
      uncleaved DNA preserved). We found significant differences in the B- and A-form
      pattern of UV light-damaged bases within the same region (polylinker) of DNA
      embedded within long (plasmid) or short (127 bp fragment) DNA molecules. The B-A
      transition of the fragment was found less cooperative than with linearized
      plasmid, which was confirmed by both CD spectroscopy and restriction cleavage
      inhibition.

PMID- 16962701
TI  - Major invasive surgery for urologic cancer in octogenarians with comorbid medical
      conditions.
AB  - OBJECTIVES: We retrospectively reviewed the records of the octogenarian patients
      who underwent major surgery for urologic cancer at two institutions. The aims of
      our study were to assess intra- and postoperative morbidity and mortality rates,
      and to identify potential risk factors that can predict postoperative
      complications and, as a consequence, surgical outcome. METHODS: Fifty-five
      patients (median age: 83 yr) underwent major surgery for urologic cancer. Radical
      nephrectomy was performed in 27 patients, radical cystectomy with urinary
      diversion was done in 20 patients, and nephroureterectomy was performed in the
      remainder. Significant comorbidity was present in 51 patients. RESULTS: The
      perioperative mortality rate was 9%. The overall mortality rate was 69%; cancer
      specific mortality was 28%. Intraoperative complications occurred in 11% of
      patients. Postoperative intensive care monitoring was required in 29% of
      patients. The early postoperative complication rate was 33%. Only the presence of
      more than two comorbidities (p<0.05) and chronic obstructive lung disease (COLD)
      (p=0.017) resulted in independent prognostic factors for morbidity. Sixteen
      percent of patients developed a late postoperative complication within the first
      6 mo. Median hospital stay was 14 d (range: 6-55), and hospital stays were
      significantly longer among patients with complications (p<0.05). The 3-yr and 5
      yr overall survival rates were 36% and 26%, respectively; these rates were
      significantly lower in patients with COLD (p<0.01). There was no significant
      difference between cancer-specific and non-cancer-specific survival rates.
      CONCLUSIONS: Major surgery for urologic malignancies can be safely performed in
      selected octogenarian patients.

PMID- 16962702
TI  - Phytoestrogens as inhibitors of the human progesterone metabolizing enzyme
      AKR1C1.
AB  - Phytoestrogens are plant-derived, non-steroidal constituents of our diets. They
      can act as agonists or antagonists of estrogen receptors, and they can modulate
      the activities of the key enzymes in estrogen biosynthesis. Much less is known
      about their actions on the androgen and progesterone metabolizing enzymes. We
      have examined the inhibitory action of phytoestrogens on the key human
      progesterone-metabolizing enzyme, 20alpha-hydroxysteroid dehydrogenase (AKR1C1).
      This enzyme inactivates progesterone and the neuroactive 3alpha,5alpha
      tetrahydroprogesterone, to form their less active counterparts, 20alpha
      hydroxyprogesterone and 5alpha-pregnane-3alpha,20alpha-diol, respectively. We
      overexpressed recombinant human AKR1C1 in Escherichia coli, purified it to
      homogeneity, and examined the selected phytoestrogens as inhibitors of NADPH
      dependent reduction of a common AKR substrate, 9,10-phenantrenequinone, and
      progesterone. The most potent inhibitors were 7-hydroxyflavone, 3,7
      dihydroxyflavone and flavanone naringenin with IC(50) values in the low microM
      range. Docking of the flavones in the active site of AKR1C1 revealed their
      possible binding modes, in which they are sandwiched between the Leu308 and
      Trp227 of AKR1C1.

PMID- 16962703
TI  - The influence of activated carbon surface properties on the adsorption of the
      herbicide molinate and the bio-regeneration of the adsorbent.
AB  - In the present study, the effect of the textural and surface chemistry properties
      of the activated carbon were evaluated in a combined treatment system to remove
      the herbicide molinate from waters. The process consists of an initial adsorption
      step followed by the bio-regeneration of the activated carbon through the
      utilization of a defined bacterial mixed culture (DC), previously described as
      able to mineralize molinate. Molinate adsorption and partial bio-regeneration was
      favoured with activated carbons with larger pores, consisting mainly of meso and
      macropores. In order to study the effect of different surface chemical
      characteristics while maintaining the original textural properties, a commercial
      activated carbon was submitted to thermal and nitric acid treatments. The thermal
      treatment improved the molinate adsorption capacity of activated carbon. However,
      the bio-regeneration of the nitric acid oxidised activated carbon was slightly
      higher. With all the activated carbon materials used it was observed that the
      biological consumption of molinate present in the liquid phase displaced the
      equilibrium towards the activated carbon partial regeneration.

PMID- 16962704
TI  - Chemically and genetically immunocompromised mice are not more susceptible than
      immunocompetent mice to infection with Cryptosporidium muris.
AB  - The prevailing paradigm is that immunosuppressed individuals are more susceptible
      to infection and are at higher risk of infection from Cryptosporidium oocysts if
      present in drinking water. To test this hypothesis, three immune conditions were
      examined: genetically immunocompromised T cell deficient CD-1 nude mice, B and T
      cell deficient Fox Chase CB-17/IcrClB SCID mice, and chemically immunosuppressed
      C57Bl/6 mice. Chemical immunosuppression was induced with a single subcutaneous
      injection of methylprednisolone acetate (MPA) at 600 mg/kg. The MPA
      immunosuppressed C57Bl/6 mice were characterized by a sustained decrease in
      circulating CD3, CD4 and CD8 T-lymphocytes of greater than 80% and a similar
      decrease in B-lymphocytes. A sharp rise in circulating mature segmented
      neutrophils followed MPA injection, dropping sharply after 10-14 days, mirroring
      the decrease in lymphocytes. The cessation of oocyst production after MPA was not
      accompanied by a radical rise in circulating CD3 or CD4 T-lymphocytes, but rather
      a rise in CD8 T-lymphocytes. The ID50 for the MPA immunosuppressed C57Bl/6 mice
      was 122 oocysts, whereas the ID50 for the C57Bl/6 immunocompetent group was 44.
      The genetically immunocompromised mice showed similar differences. The ID50 for
      CD-1 nude mice was 166 oocysts compared to 64 in CD-1 immunocompetent mice. For
      Fox Chase CB-17/IcrClB SCID and the immunocompetent CB-17 mice, the ID50's were
      83 and 60 oocysts, respectively. These results suggest that the lack of an immune
      response does not increase the ability of C. muris to establish a productive
      infection and produce oocysts.

PMID- 16962705
TI  - In vitro culture, serologic and molecular analysis of Acanthamoeba isolated from
      the liver of a keel-billed toucan (Ramphastos sulfuratus).
AB  - Members of the genus Acanthamoeba are usually free-living amebae and are found in
      a variety of ecological niches including soil, fresh and brackish water, dust in
      air, filters of heating, ventilating, and air conditioning units, swimming pools
      and hot tubs, etc. Occasionally, they are also known to cause central nervous
      system infections in humans and other animals. We isolated into culture an amoeba
      from the liver tissue of a keel-billed toucan and identified it as Acanthamoeba
      sp. based on culture characteristics and immunofluorescent analysis. Further, we
      characterized the cultured amoeba and also the amoeba in the liver tissue as
      Acanthamoeba, genotype T4, by sequencing a diagnostic region of the nuclear small
      subunit ribosomal RNA gene.

PMID- 16962706
TI  - Seroprevalence of Neospora caninum in non-carnivorous wildlife from Spain.
AB  - Serum samples from 1034 non-carnivorous wildlife from Spain were tested for
      antibodies to Neospora caninum by competitive screening enzyme linked
      immunosorbent assay (ELISA) and confirmed by an indirect fluorescent antibody
      test (IFAT). High agreement was observed between results in both techniques
      (kappa value higher than 0.9). Prevalences of N. caninum antibodies positive by
      both techniques were 11.8% of 237 red deer (Cervus elaphus), 7.7% of 13 barbary
      sheep (Ammotragus lervia), 6.1% of 33 roe deer (Capreolus capreolus) and 0.3% of
      298 wild boar (Sus scrofa). In one of 53 hares (Lepus granatensis), antibodies
      were found in the ELISA but could not be confirmed by IFAT due to lack of sample.
      Antibodies to N. caninum were not found in any of 251 wild rabbits (Oryctolagus
      cuniculus), 79 fallow deer (Dama dama), 27 mouflon (Ovis ammon), 40 chamois
      (Rupicapra pyrenaica) and three Spanish ibex (Capra pyrenaica). Statistically
      significant differences were observed between N. caninum seroprevalence in red
      deer and management of hunting estates (open versus fenced) with higher
      prevalence in fenced estates, and among sampling sites. Seroprevalence was
      particularly high in some areas (MO estate in South-Central Spain or some estates
      of Catalonia, North-East Spain), while no contact with N. caninum was observed in
      others. Results indicate that in certain areas of Spain, N. caninum is present in
      wildlife, especially in red deer. These results have important implications in
      both sylvatic cycles and may influence the prevalence of infection in cattle
      farms in those areas. To our knowledge, this is the first report of antibodies to
      N. caninum in wildlife from Spain and the first report of N. caninum antibodies
      in barbary sheep and wild boar.

PMID- 16962707
TI  - Canine babesiosis: a Brazilian perspective.
AB  - Canine babesiosis is highly endemic in Brazil, caused by Babesia canis and
      Babesia gibsoni, both transmitted by Rhipicephalus sanguineus ticks. The present
      review argues for a more adequate method of characterizing the Babesia species
      infecting dogs and cats in different Brazilian endemic zones. It advocates for a
      comprehensive understanding of the biology of R. sanguineus ticks under Brazilian
      conditions in order to define the more effective preventive strategies against
      canine babesiosis and calls for partnerships between the public and private
      sectors for research on canine babesiosis and other vector-borne diseases in
      Brazil.

PMID- 16962708
TI  - Association between the presence of serum antibodies against Neospora spp. and
      fetal loss in equines.
AB  - A study of the association between the presence of serum antibodies against
      Neospora spp. and fetal loss was performed using serum samples of horses
      submitted to the laboratory for the detection of antibodies to Equine Herpesvirus
      1 and Equine Infectious Anemia Virus. The sera submitted for equine infectious
      anemia testing were from horses declared healthy and those submitted for the
      detection of antibodies to Equine Herpesvirus-1 were from mares with late
      clinical signs of reproductive disorders or males living in close contact with
      diseased mares. For the detection of Neospora spp. infection, the
      immunofluorescent antibody test was employed, using a cut-off titer of 50 as
      significant for the presence of antibodies. Among the 483 mares in the diseased
      group, 15.1% (73/483) was reactant, while 5.8% (19/325) was seropositive in the
      healthy group. The results show that late clinical signs of reproductive
      disorders in mares are positively associated (p<0.001) to infection with protozoa
      belonging to the genus Neospora and point to the fact that the participation of
      this group of coccidia in the genesis of reproductive disorders in equine must be
      investigated.

PMID- 16962710
TI  - Intraspecific variation of Echinococcus granulosus in livestock from Peru.
AB  - Echinococcus granulosus infection is a problem of public health in livestock
      rearing regions of Latin America, like in Peru. This species is characterized by
      the morphometry of the large and small rostellar hooks in both metacestodes and
      adult worms. The aim of this work was to study biometrical characteristics of
      rostellar hooks in hydatid cysts (lung and liver) from some Peruvian provinces
      (Arequipa, Cuzco, Huancavelica, Junin and Puno). The biometrical analysis was
      obtained in a digital system for image analysis. The following parameters were
      studied: area, perimeter, length and width total of the handle, the blade and the
      distance between the blade and the guard of large and small hooks. For
      statistical analysis Student's t-test and Analysis of Variance (ANOVA) with Pos
      test of Tukey were used, considering the values of p< or =0.05 as of statistic
      significance. All morphometric characters of large and small hooks were highly
      significant (p<0.000), when data were compared among the samples from the
      different provinces. Rostellar hooks in specimens from Huancavelica presented
      smallest measurements, whereas hooks in specimens from Junin were bigger in
      relation to the total and blade measurements. Generally, samples from Arequipa
      presented the biggest large hooks in relation to the handle parameters. The
      rostellar hooks of cattle and sheep hosts varied depending on the geographic
      localization, host and organ. Hooks recovered from the lungs were larger than
      those collected in the liver. It was concluded that morphometry using computer
      image analysis allows the characterization of E. granulosus. The rostellar hooks
      presented morphometric polymorphism.

PMID- 16962709
TI  - Characterization of an ecto-5'-nucleotidase (EC 3.1.3.5) activity in intact
      trophozoites of Trichomonas gallinae.
AB  - This study describes the enzymatic properties of an ecto-5'-nucleotidase in
      Trichomonas gallinae. The enzyme hydrolyzes nucleoside monophosphates at pH 7.2
      and is activated by divalent cations, such as magnesium. Ecto-5'-nucleotidase
      activity was insensitive to levamisole, tetramisole (alkaline phosphatase
      inhibitors), and AMPCP (adenosine 5'-[alpha,beta-methylene]diphosphate), an ecto
      5'-nucleotidase inhibitor, whereas 0.1mM ammonium molybdate (considered a potent
      inhibitor of 5'-nucleotidase activity) completely inhibited the enzyme activity.
      The apparent K(M) (Michaelis constant) and Vmax (maximum velocity) values for
      Mg2+-AMP were 466+/-57 microM and 3.7+/-0.59 nmolPi/min/10(6) trichomonads,
      respectively. Considering that trichomonads lack the ability to synthesize
      purines and pyrimidines de novo, the presence of an ecto-5'-nucleotidase in
      intact trophozoites of T. gallinae could be important in regulating the
      extracellular nucleotide levels and generating adenosine, essential for the
      survival strategies of the parasite.

PMID- 16962711
TI  - Fermented papaya preparation attenuates beta-amyloid precursor protein: beta
      amyloid-mediated copper neurotoxicity in beta-amyloid precursor protein and beta
      amyloid precursor protein Swedish mutation overexpressing SH-SY5Y cells.
AB  - Recent studies indicate that the deposition of beta-amyloid (Abeta) is related in
      the pathogenesis of Alzheimer's disease (AD), but the underlying mechanism is
      still not clear. The abnormal interactions of Abeta with metal ions such as
      copper are implicated in the process of Abeta deposition and oxidative stress in
      AD brains. In the present study, we established a new AD model, using which we
      found that copper triggered the Abeta neurotoxicity in SH-SY5Y cells
      overexpressing the Swedish mutant form of human APP (APPsw) in a concentration
      dependent manner. Fermented papaya preparation (FPP) has shown high free radical
      scavenging ability in vivo and in vitro. FPP post-treatment increased cell
      viability and decreased the intracellular [Ca2+]i, reactive oxygen species (ROS)
      generation such as hydroxyl free radical and superoxide anion and nitric oxide
      (NO) accumulation in the cell. Our results also show that FPP prevents the cell
      apoptosis through bax/bcl-2 sensitive pathway.

PMID- 16962712
TI  - Ectopic expression of doublecortin protects adult rat progenitor cells and human
      glioma cells from severe oxygen and glucose deprivation.
AB  - Doublecortin (DCX) is a microtubule-associated protein expressed in migrating
      neuroblasts. DCX expression is increased in subventricular zone (SVZ) cells
      migrating to the boundary of an ischemic lesion after induction of middle
      cerebral artery occlusion (MCAO) in adult rats and mice. We tested the hypothesis
      that DCX, in addition to being a marker of migrating neuroblasts, serves to
      protect neuroblasts from conditions of stress, such as oxygen and glucose
      deprivation (OGD). Using gene transfer technology, we overexpressed DCX in rat
      SVZ and U-87 human glioma cells. The cells remained viable against severe OGD, up
      to 32 h exhibiting 1% apoptosis compared with 100% apoptosis in control. In
      addition, these genetically modified cells upregulated expression of E-, VE- and
      N-cadherin, molecules that promote endothelial survival signals via the VE
      cadherin/vascular endothelial growth factor receptor-2/phosphoinositide 3-kinase
      (PI3-K)/AKT/beta-catenin pathway and inactivate the proapoptotic factor Bad. DCX
      overexpression also significantly increased cell migration in SVZ tissue explants
      and U-87 cells and significantly upregulated microtubule-associated protein-2
      (MAP2) and nestin protein levels in SVZ and U-87 cells compared with wild-type
      control cells. Knocking down DCX expression in DCX overexpressing SVZ and U-87
      cells with DCX small interfering RNA (siRNA), confirmed the specificity of DCX on
      cell survival against OGD, and the DCX induced upregulation of E-, VE- and N
      cadherin, MAP2 and nestin. In NIH3T3 cells, DCX overexpression had no effect on
      cell survival against OGD, and indicating that the protective effects of DCX was
      restricted to brain cells e.g. SVZ and U-87 cells. Our data suggest a novel and
      an important role for DCX as a protective agent for migrating neuroblasts and
      tumor cells.

PMID- 16962713
TI  - An activity-dependent increased role for L-type calcium channels in exocytosis is
      regulated by adrenergic signaling in chromaffin cells.
AB  - Chromaffin cells of the adrenal medulla represent a primary output of the
      sympathetic nervous system. Their electrical stimulation evokes the fusion of
      large dense core granules with the cell membrane and the exocytic release of
      multiple transmitter molecules into the circulation. There the transmitters
      contribute to the regulation of basic metabolism of the organism. Under
      physiological activity, granule fusion and transmitter release are limited by
      activity-dependent Ca(2+) influx, entering through multiple isoforms of voltage
      gated calcium channels. In this study we utilize perforated-patch voltage-clamp
      recordings and depolarize mouse chromaffin cells in situ with action potential
      like waveforms to mimic physiological firing. We measure calcium influx through
      specific isoforms and measure cell capacitance as an index of granule fusion.
      Combining these approaches we calculate specific stimulus-secretion efficiencies
      for L-type, N-type, P/Q-type and R-type calcium channels under varied
      physiological activity levels. Current influx through all channel subtypes
      exhibited an activity-dependent depression. As expected P/Q-type channels, while
      responsible for modest Ca(2+) influx, are tightly coupled to catecholamine
      secretion under all conditions. We further find that stimulation designed to
      match sympathetic input under the acute stress response recruits L-type channels
      to a state of enhanced stimulus-secretion efficiency. N- and R-type channels do
      not undergo activity-dependent recruitment and remain loosely coupled to the
      secretion. Thus, only L-type channels exhibit activity-dependent changes in their
      stimulus-secretion function under physiological stimulation. Lastly, we show that
      treatment with the beta-adrenergic agonist, isoproterenol, specifically blocks
      the increase in the stimulus-secretion function of L-type channels. Thus,
      increased cell firing specifically enhances stimulus-secretion coupling of L-type
      Ca(2+) channels in chromaffin cells in situ. This mechanism is regulated by an
      adrenergic signaling pathway.

PMID- 16962714
TI  - Cyclic AMP-inducible genes respond uniformly to seasonal lighting conditions in
      the rat pineal gland.
AB  - The encoding of photoperiodic information ensues in terms of the daily profile in
      the expression of cyclic AMP (cAMP)-inducible genes such as the arylalkylamine N
      acetyltransferase (AA-NAT) gene that encodes the rate-limiting enzyme in
      melatonin formation. In the present study, we compared the influence of the
      photoperiodic history on the cAMP-inducible genes AA-NAT, inducible cyclic AMP
      early repressor (ICER), fos-related antigen-2 (FRA-2), mitogen-activated protein
      kinase phosphatase-1 (MKP-1), nerve growth factor inducible gene-A (NGFI-A) and
      nerve growth factor inducible gene-B (NGFI-B) in the pineal gland of rats. For
      this purpose, we monitored the daily profiles of each gene in the same pineal
      gland under a long (light/dark 16:8) and a short (light/dark 8:16) photoperiod by
      measuring the respective mRNA amounts by real-time polymerase chain reaction
      analysis. We found that, for all genes under investigation, the duration of
      increased nocturnal expression is lengthened and, in relation to light onset, the
      nocturnal rise is earlier under the long photoperiod (light/dark 16:8).
      Furthermore, with the exception of ICER, all other cAMP-inducible genes tend to
      display higher maximum expression under light/dark 8:16 than under light/dark
      16:8. Photoperiod-dependent changes persist for all of the cAMP-inducible genes
      when the rats are kept for two cycles under constant darkness. Therefore, all
      cAMP-inducible genes are also influenced by the photoperiod of prior entrained
      cycles. Our study indicates that, despite differences regarding the expressional
      control and the temporal phasing of the daily profile, cAMP-inducible genes are
      uniformly influenced by photoperiodic history in the rat pineal gland.

PMID- 16962715
TI  - Working memory training decreases hippocampal neurogenesis.
AB  - The relationship between adult hippocampal neurogenesis and cognition appears
      more complex than suggested by early reports. We aimed to determine if the
      duration and task demands of spatial memory training differentially affect
      hippocampal neurogenesis. Adult male rats were trained in the Morris water maze
      in a reference memory task for 4 days, or alternatively working memory for either
      4 or 14 days. Four days of maze training did not impact neurogenesis regardless
      of whether reference or working memory paradigms were used. Interestingly, 2
      weeks of working memory training using a hidden platform resulted in fewer
      newborn hippocampal neurons compared with controls that received either cue
      training or no maze exposure. Stress is a well-established negative regulator of
      hippocampal neurogenesis. We found that maze training in general, and a working
      memory task in particular, increased levels of circulating corticosterone after 4
      days of training. Our study indicates that working memory training over a
      prolonged period of time reduces neurogenesis, and this reduction may partially
      be mediated by increased stress.

PMID- 16962716
TI  - On the participation of hippocampal p38 mitogen-activated protein kinase in
      extinction and reacquisition of inhibitory avoidance memory.
AB  - Inhibitory avoidance (IA) learning relies on the formation of an association
      between stepping down from a platform present in a certain context (conditioned
      stimulus; CS) with an aversive unconditioned stimulus (US; i.e. a footshock). A
      single CS-US pairing establishes a robust long-term memory expressed as an
      increase in step-down latency at testing. However, repeated retrieval of the
      avoidance response in the absence of the US induces extinction of IA memory. That
      is, recurring presentation of the CS alone results in a new learning indicating
      that the CS no longer predicts the US. Although the signaling pathways involved
      in the consolidation of IA and other fear-motivated memories have been profusely
      studied, little is known about the molecular requirements of fear memory
      extinction. Here we report that, as happens with its consolidation, extinction of
      IA long-term memory requires activity of the p38 subfamily of mitogen-activated
      protein kinases (MAPK) in the CA1 region of the dorsal hippocampus. Moreover, we
      found that inhibition of hippocampal p38MAPK blocked memory reacquisition after
      extinction without affecting either the increase in IA memory retention induced
      by a second training session or animal's locomotor/exploratory activity and
      anxiety state.

PMID- 16962717
TI  - Prolonged behavioral stress enhances synaptic connectivity in the basolateral
      amygdala.
AB  - Recently identified cellular and molecular correlates of stress-induced
      plasticity suggest a putative link between neuronal remodeling in the amygdala
      and the development of anxiety-like behavior. Rodent models of immobilization
      stress, applied for 10 consecutive days, have been reported to enhance anxiety,
      and also cause dendritic elongation and spine formation in the basolateral
      amygdala (BLA). Paradoxically, longer exposure to stress, which is also
      anxiogenic, fails to affect key molecular markers of neuronal remodeling in the
      BLA. This has raised the possibility of homeostatic mechanisms being triggered by
      more prolonged stress that could potentially dampen the morphological effects of
      stress in the BLA. Therefore, we examined the cellular and behavioral impact of
      increasing the duration of stress in rats. We find that prolonged immobilization
      stress (PIS), spanning 21 days, caused significant enhancement in dendritic
      arborization of spiny BLA neurons. Spine density was also enhanced along these
      elongated dendrites in response to PIS. Finally, this striking increase in
      synaptic connectivity was accompanied by enhanced anxiety-like behavior in the
      elevated plus-maze. Thus, we did not detect any obvious morphological correlate
      of adaptive changes within the BLA that may have been activated by prolonged and
      repeated application of the same stressor for 21 days. These findings add to
      accumulating evidence that structural encoding of aversive experiences, through
      enhanced availability of postsynaptic dendritic surface and synaptic inputs on
      principal neurons of the BLA, may contribute to the affective symptoms of stress
      disorders.

PMID- 16962718
TI  - Pituitary adenylate cyclase-activating polypeptide directly modulates the
      activity of proopiomelanocortin neurons in the rat arcuate nucleus.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) and the
      proopiomelanocortin (POMC)-derived peptide alpha-melanocyte-stimulating hormone
      (alpha-MSH) both regulate multiple neuroendocrine functions and feeding behavior.
      Two subtypes of PACAP receptor mRNAs, pituitary adenylate cyclase-activating
      polypeptide-specific receptor (PAC1-R) and pituitary adenylate cyclase-activating
      polypeptide/vasoactive intestinal polypeptide mutual receptor (VPAC2-R), are
      actively expressed in the arcuate nucleus of the hypothalamus, where POMC cell
      bodies are located. This observation led us to investigate the possible
      regulatory action of PACAP on rat POMC neurons. Double-labeling in situ
      hybridization histochemistry revealed that approximately 50% of POMC-producing
      neurons express PAC1-R and/or VPAC2-R mRNAs. The proportion of POMC neurons that
      also contain PAC1-R mRNA was homogeneous along the rostro-caudal axis of the
      arcuate nucleus while POMC-positive cell bodies expressing the VPAC2-R subtype
      were more abundant in the rostral region. Incubation of mediobasal hypothalamic
      explants with PACAP (10(-7) M; 30 min) increased POMC mRNA expression, and this
      effect was blocked by PACAP6-38 (10(-6) M). In contrast, incubation with
      vasoactive intestinal polypeptide (10(-7) M) did not affect POMC mRNA level.
      Incubation of hypothalamic fragments with PACAP (10(-7) M) caused a significant
      increase in alpha-MSH content in the tissue and in the incubation medium.
      Altogether, the present results reveal that exogenous PACAP, acting probably
      through PAC1-R, regulates the activity of POMC neurons in the rat hypothalamus.
      These data suggest that the effects of PACAP on the gonadotropin-releasing
      hormone neuroendocrine axis and the regulation of feeding behavior may be
      mediated, at least in part, through modulation of POMC neurons.

PMID- 16962719
TI  - Comparison of antinociceptive actions of standard analgesics in attenuating
      capsaicin and nerve-injury-induced mechanical hypersensitivity.
AB  - Intradermal capsaicin injection produces immediate spontaneous pain behaviors,
      and a secondary mechanical hypersensitivity (SMH) that is employed in the clinic
      as a model potentially predictive of human neuropathic pain. Presently, we have
      characterized capsaicin-induced SMH in rats, and compared pharmacological actions
      of standard analgesics in this and two nerve injury models, the L5/L6 spinal
      nerve ligation (SNL) and sciatic nerve chronic constriction injury (CCI) models.
      Intraplantar capsaicin produced dose-related SMH (enhanced paw withdrawal
      response to von Frey monofilament stimulation at an area away from injection
      site) that lasted for over 4 h. While pretreatment with a potent selective
      transient receptor potential vanilloid receptor-1 (TRPV1) antagonist A-425619 (1
      isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea) prevented development of
      acute nocifensive (flinching) behavior immediately following capsaicin injection
      (ED(50)=4.9 mg/kg), the compound failed to attenuate the SMH when administered 2
      h following capsaicin (10 microg/10 microl). Additional standard analgesics were
      also tested 3 h following intraplantar capsaicin in the SMH model. Comparison of
      their potencies in attenuating mechanical hypersensitivity in capsaicin, SNL and
      CCI models revealed similar ED(50)s for morphine (2.3 mg/kg, 1.6 mg/kg and 3.2
      mg/kg, respectively), gabapentin (33.1 mg/kg, 33.9 mg/kg and 26.3 mg/kg,
      respectively) and lamotrigine (9.1 mg/kg, 8.9 mg/kg and 15.5 mg/kg,
      respectively). Duloxetine produced 50-65% effect at the highest tested dose (50
      mg/kg), whereas the highest tested doses of morphine (10 mg/kg), gabapentin (85.5
      mg/kg) and lamotrigine (30 mg/kg) all produced >70% efficacy in capsaicin SMH,
      SNL and CCI models. In contrast, celecoxib and ibuprofen showed weak effects in
      all three models. All standard analgesics generally had weak efficacy in
      attenuating capsaicin-induced immediate acute flinching behavior when
      administered before capsaicin. These results provide further support to the
      suggestions that distinct pharmacological mechanisms underlie capsaicin-induced
      acute nocifensive and SMH behaviors, and certain neuronal mechanisms underlying
      neuropathic pain states are also contributory to capsaicin-induced SMH.

PMID- 16962720
TI  - Serotonin regulation of the human stress response.
AB  - Acute tryptophan depletion (ATD) is a technique that has been used to evaluate
      the effects on humans of acutely reducing serotonin neurotransmission. We have
      developed a model using a single breath of 35% CO(2) that activates the hormonal
      axis and produces autonomic and behavioural arousal, thus modelling a stress
      response. This study combines ATD and single breath 35% CO(2) inhalation to study
      stress responses in volunteers. A randomised, double-blinded, placebo-controlled,
      cross-over trial involving 14 healthy adult volunteers aged between 18 and 65
      years was undertaken. Subjects underwent double-blind tryptophan depletion over 2
      days and were then crossed over 1 week later. During each study day, at the time
      of peak depletion, participants were single blinded to receive a single breath of
      35% CO(2) or air. This was followed 40 min later by the other gas. Psychological
      outcomes were assessed with the Spielberger State Anxiety Inventory (SSAI),
      Visual Analogue Scales (VAS), Panic Inventory (PI), Panic and Agoraphobia Scale
      (PSI) and Beck Depression Inventory (BDI). Physiological outcome was measured by
      serial plasma cortisol, prolactin and tryptophan levels, pulse and blood
      pressure. Tryptophan depletion did not exacerbate 35% CO(2) inhalation effects on
      anxiety symptoms. Single breath CO(2) robustly increased plasma cortisol levels
      in comparison to an air inhalation; this was less certain for prolactin levels.
      ATD influenced the HPA axis (associated with higher cortisol levels), apparently
      independent of CO(2) or air inhalation stressors. ATD and 35% CO(2) inhalation
      both induced a pressor response and bradycardia in these normal volunteers.
      Thirty-five percent CO(2) inhalation and ATD independently activate the human
      stress response, but do not appear to produce synergistic effects when combined,
      at least for the conditions produced in this study.

PMID- 16962721
TI  - Estrogen or testosterone may be effective agents in the management of both
      multiple myeloma and Alzheimer's disease.

PMID- 16962722
TI  - Meniere's disease may be caused by common intraosseous dental pathology-
      Diagnosis using the comparative compression sign.
AB  - Meniere's disease has been ascribed to a disturbance of the vestibular apparatus
      or its connections within the Central Nervous System. Several hypotheses have
      been advanced regarding its aetiopathogenesis, but treatments based on these
      hypotheses have often not produced the desired results. Two cases are described
      where common intraosseous pathology within the lower half of the functional face,
      i.e. within the mandible and maxillae, was shown to be the cause of Meniere's
      disease. Together, these cases contributed to the chance discovery of the
      comparative compression sign which, when able to be elicited, may be considered
      pathognomonic for a dental origin of the condition. It is suggested that, in
      addition to other hypothesized causes involving the vestibular apparatus and the
      CNS, Meniere's disease and vertigo may also be caused by common, readily
      identifiable intraosseous dental pathology. These unexpected findings open up a
      new field for future research.

PMID- 16962723
TI  - Triquinane-based compounds as possible serotonin 5-HT(6) receptor antagonists for
      the treatment of Alzheimer's disease.
AB  - The recently discovered serotonin 5-HT(6) receptor is a novel target for the
      treatment of cognitive decline associated with neurodegenerative diseases such as
      Alzheimer's disease (AD). Several studies have shown that antagonism of this
      receptor leads to improved learning and memory. Two serotonin 5-HT(6) receptor
      antagonists are currently in Phase II clinical trials for cognitive enhancement.
      Striking structural similarities between the polycyclic features of some 5-HT(6)
      antagonists and those of the cis-syn-cis triquinane ring system led us to propose
      that triquinane-derived compounds may represent a novel class of 5-HT(6) receptor
      antagonists. Using computational methodologies, we propose a structure with
      features that may impart potent 5-HT(6) receptor antagonistic activities to the
      triquinane ring complex. Related compounds, once synthesized, may have possible
      utility in the treatment of cognitive decline associated with AD.

PMID- 16962724
TI  - Zinc sulfate could be potential agent for the treatment of Rett syndrome through
      increasing central BDNF levels.

PMID- 16962725
TI  - From latent incubation launched into hostile symptomatic pathology: A probable
      survival strategy for common respiratory infectious agents.
AB  - Common respiratory infections usually show a latent incubation period, followed
      by an acute stage. Finally, due to new synthesis of specific antibodies, the
      relative microorganisms undergo a massive eradication from hostile organism.
      Meanwhile, clinical symptoms induced by innate immunity mechanisms during these
      pathologies are assumed properly as host attempts for the expulsion of infectious
      agents. Some studies have demonstrated the existence of immuno-modulatory
      abilities by different infectious agents, which can inhibit inflammatory response
      and the development of respective symptoms by hostile organisms, especially
      during incubatory period. In contrast, after the incubatory period microorganisms
      induced immuno-inhibitory effects may undergo a reduction, and in the meantime
      clinical symptoms appear a few days before the hostile organism synthesizes
      specific antibodies, which can eradicate these pathogens. From the evolutionary
      viewpoint of microorganisms, maybe induction of pathologic symptoms even before
      the period of specific hostile antibody synthesis, but not at beginning of
      infection, could play a particular adaptive role. Such scenario first could
      assure a maximal multiplication for the infectious agents, whereas later attempts
      to support the host abandonment, even due to induction of clinical expulsive
      symptoms. The existence of related pathologies since ancient times leads to the
      suggestion that perhaps the induction of such diseases is not a purpose per se
      for such pathogens, but rather an instrument to provide for host abandonment on
      time to catch a next one, assuring therefore maximal successive reproduction.

PMID- 16962726
TI  - Mitogenic effect of Carthamus lanatus extracts, fractions and constituents.
AB  - Extracts, fractions and constituents of Carthamus lanatus were tested for their
      mitogenic effect on bone marrow cells in mice. Most of the studied samples
      inhibited cell proliferation and only the flavonoid glycoside rutin caused
      increasing of mitotic activity.

PMID- 16962727
TI  - Activity patterns of bushbuck (Tragelaphus scriptus) in Queen Elizabeth National
      Park.
AB  - Activity patterns and time budgets of bushbuck (Tragelaphus scriptus) were
      studied in a free-ranging population in Queen Elizabeth National Park, Uganda
      from August 2000 to January 2002. We investigated differences in activity
      patterns in relation to daytime, season, sun radiation, moonlight, age and sex.
      Bushbuck were found to show peak activities around sunrise and at dawn. No
      difference in the mean activity rates was found between the dry and wet season.
      Daytime activity was not predicted by differences in sun radiation, nor was
      nighttime activity predicted by the presence or absence of moonlight. We found
      the activity of adult territorial males to be strongly positively correlated with
      that of females, whereas the activity of young-adult non-territorial males was
      not significantly correlated with the activity of females. This suggests that
      young-adult males shift their peak activity to phases when adult territorial
      males are less active.

PMID- 16962728
TI  - A high level of strain variation within the Mycoplasma ovipneumoniae population
      of the UK has implications for disease diagnosis and management.
AB  - Mycoplasma ovipneumoniae is one of only two mycoplasma species associated with
      small ruminant disease in Britain and has been associated with an increasing
      number of disease outbreaks since 2002. This investigation used well-defined
      techniques to assess the variability of UK M. ovipneumoniae isolates, in an
      attempt to identify strain clusters within the population. Strains received for
      routine diagnosis between 2002 and 2004 were analysed using random amplified
      polymorphic DNA (RAPD) and pulsed field gel electrophoresis (PFGE). Of the 43
      samples screened 40 RAPD Hum-1, 41 RAPD Hum-4 and 40 PFGE profiles were observed.
      Composite data analysis divided strains into 10 similarity clusters with SDS-PAGE
      and Western blotting indicating that this DNA variability is translated into a
      pattern of variable protein expression. In order to assess the strains isolated
      within flocks two sets of samples, from diverse locations, were included in this
      test panel. The presence of variable isolates existing on the same farm may
      reflect animal movement and the introduction of asymptomatic, carrier, animals
      where M. ovipneumoniae is already established within a flock. These findings have
      significant implications regarding disease diagnosis and management.

PMID- 16962729
TI  - Stability of angiogenic agents, ginsenoside Rg1 and Re, isolated from Panax
      ginseng: in vitro and in vivo studies.
AB  - The study was designed to investigate the stability of ginsenoside Rg(1) (Rg(1))
      and Re (Re), two natural herbal compounds isolated from Panax ginseng, based on
      their activity to promote angiogenesis in vitro and in vivo. After being treated
      at different temperatures, pHs, and solvent species for distinct durations, the
      remaining activities of Rg(1) and Re on human umbilical vein endothelial cell
      (HUVEC) proliferation, migration, and tube formation were examined in vitro.
      Additionally, the remaining activity of each treated test agent, mixed in a
      growth factor-reduced Matrigel, in stimulating angiogenesis was evaluated
      subcutaneously in a mouse model. Basic fibroblast growth factor (bFGF) was used
      as a control. It was found in vitro that HUVEC proliferation, migration in a
      Transwell plate, and tube formation on Matrigel were all significantly enhanced
      in the presence of bFGF, Rg(1), or Re. However, after being treated at different
      temperatures, pHs, or solvent species, the remaining activity of bFGF on HUVEC
      behaviors reduced significantly. This observation was more significant with
      increasing the duration of treatment. In contrast, the activities of Rg(1) and Re
      remained unchanged throughout the entire course of the study. The in vivo results
      observed on day 7 after implantation showed that the blank control (Matrigel
      alone) was slightly vascularized. In contrast, the density of neo-vessels in the
      Matrigel plug mixed with bFGF, Rg(1), or Re was significantly enhanced. However,
      after being treated, the density of neo-vessels was significantly reduced in the
      Matrigel plug mixed with bFGF, while those of Rg(1) and Re remained unchanged.
      The aforementioned results suggested that Rg(1) and Re could be a novel group of
      nonpeptide angiogenic agents with a superior stability and may be used for the
      management of tissue regeneration.

PMID- 16962730
TI  - [Resistance of infectious agents involved in low respiratory tract infections in
      France].
AB  - This review concerning the major lower respiratory tract pathogens in France has
      for aim to describe the epidemiology of resistance to beta-lactams, macrolides,
      ketolides, and fluoroquinolones especially in Streptococcus pneumoniae and
      Haemophilus influenzae. It should also provide new insights on the mechanisms of
      acquired resistance and the level of resistance conferred, highlighting the
      related ecological impact. In the context of this XVth consensus conference, this
      review should contribute to the elaboration of guidelines for the treatment of
      lower respiratory tract infections in adults.

PMID- 16962731
TI  - Neonatal trauma.
AB  - A variety of traumatic lesions can occur during the neonatal period. Some of
      those lesions are clearly birth injuries due to delivery and others are caused by
      necessary procedures during intensive care in critically ill neonates. As usual
      patient history must be known and knowledge about the typical complications is
      necessary in order to select the appropriate imaging modality and thus enabling
      correct interpretation of those investigations by the radiologist. The purpose of
      this article is to present typical neonatal injuries, describe the underlying
      pathomechanisms and aetiology as well as the imaging findings.

PMID- 16962732
TI  - Image-guided interventions in neonates.
AB  - Minimally invasive interventional radiological procedures can be invaluable in
      the care of neonates and infants. These procedures have proven to be useful in a
      wide variety of clinical situations, improving patient care, comfort and safety.
      Most techniques in adult interventional radiology have been adapted for use in
      pediatric patients, covering the spectrum of diagnostic and therapeutic
      intervention. Procedural techniques are similar, but require considerations of
      patient size, sedation, and support personnel in order to render optimal care.
      Proper physician training is imperative to provide the necessary confidence and
      expertise, and post-procedural follow-up is required to maximize positive
      outcomes. This paper discusses many of the procedures that may be performed in
      neonates, and offers suggestions and techniques for successful outcomes.

PMID- 16962733
TI  - Determination of loratadine and its active metabolite in human plasma by high
      performance liquid chromatography with mass spectrometry detection.
AB  - A new sensitive and selective liquid chromatography coupled with mass
      spectrometry (LC/MS/MS) method for quantification of loratadine (LOR) and its
      active metabolite descarboethoxyloratadine (DSL) in human plasma was validated.
      After addition of the internal standard, metoclopramide, the human plasma samples
      (0.3 ml) were precipitated using acetonitrile (0.75 ml) and the centrifuged
      supernatants were partially evaporated under nitrogen at 37 degrees C at
      approximately 0.3 ml volume. The LOR, DSL and internal standard were separated on
      a reversed phase column (Zorbax SB-C18, 100 mmx3.0 mm i.d., 3.5 microm) under
      isocratic conditions using a mobile phase of an 8:92(v/v) mixture of acetonitrile
      and 0.4% (v/v) formic acid in water. The flow rate was 1 ml/min and the column
      temperature 45 degrees C. The detection of LOR, DSL and internal standard was in
      MRM mode using an ion trap mass spectrometer with electrospray positive
      ionisation. The ion transitions were monitored as follows: 383-->337 for LOR, 311
      ->(259+294+282) for DSL and 300-->226.8 for internal standard. Calibration curves
      were generated over the range of 0.52-52.3 ng/ml for both LOR and DSL with values
      for coefficient of determination greater than 0.994 by using a weighted (1/y)
      quadratic regression. The lower limits of quantification were established at 0.52
      ng/ml LOR and DSL, respectively, with an accuracy and precision less than 20%.
      Both analytes demonstrated good short-term, long-term, post-preparative and
      freeze-thaw stability. Besides its simplicity, the sample treatment allows
      obtaining a very good recovery of both analytes, around 100%. The validated
      LC/MS/MS method has been applied to a pharmacokinetic study of loratadine tablets
      on healthy volunteers.

PMID- 16962734
TI  - Effects of edaravone on N-methyl-D-aspartate (NMDA)-mediated cytochrome c release
      and apoptosis in neonatal rat cerebrocortical slices.
AB  - N-Methyl-D-aspartate-mediated neurotoxicity is known to involve nitric oxide
      production and to be augmented in an environment of reactive oxygen species. We
      used TUNEL staining and homogenous cytosolic immunoreactivity of cytochrome c in
      an acute brain slice preparation to investigate the influence of edaravone (3
      methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, on N-methyl-D
      aspartate-induced apoptosis. Cerebrocortical slices were obtained from parietal
      lobes of 7-day-old Sprague-Dawley rats, superfused with well-oxygenated
      artificial cerebrospinal fluid, and metabolically recovered. Subsequent 30-min
      exposures to 10 microM N-methyl-D-aspartate in treated and untreated slices were
      followed by 4 h of recovery superfusion with oxygenated artificial cerebrospinal
      fluid. Outcomes were compared for three groups of slices: "the N-methyl-D
      aspartate-only group"; "the edaravone treatment group", which had 20 microM
      edaravone present throughout and subsequent to N-methyl-D-aspartate exposure; the
      "control group", in which slices were superfused only with oxygenated artificial
      cerebrospinal fluid. At the conclusion of recovery (t = 4 h), the percentage of
      TUNEL-positive cells in the edaravone treatment group (7.0+/-3.3%) was
      significantly reduced from the percentage for the N-methyl-D-aspartate-only group
      (21.9+/-4.1%), and insignificantly greater than the percentage for the control
      group (3.4+/-2.1%). Percentages of cytochrome c positive cells at t = 1 h were
      significantly increased (p < 0.01) in the N-methyl-d-aspartate-only group (30.6+/
      1.9%) compared to percentages for both the control group (11.4+/-2.6%) and the
      edaravone treatment group (15.2+/-2.1%). Edaravone's reduction in TUNEL staining
      and cytochrome c release provides evidence of reactive oxygen species mechanisms
      and antioxidant benefits in cytochrome c-mediated apoptosis during N-methyl-D
      aspartate excitotoxicity.

PMID- 16962735
TI  - An LNA-based loss-of-function assay for micro-RNAs.
AB  - MicroRNAs (miRNAs) have recently emerged as being essential for development and
      for the control of cell proliferation/differentiation in various organisms.
      However, little is known about miRNA function and mode of action at the cellular
      level. We have designed a miRNA loss-of-function assay, based on chemically
      modified locked nucleic acids (LNA) antisense oligonucleotides and usable in
      tissue culture cells. We show that LNA/DNA mixed oligonucleotides form highly
      stable duplexes with miRNAs in vitro. Ex vivo, the target miRNA becomes
      undetectable in cells transfected with the antisense oligonucleotide. The effect
      is dose-dependent, long-lasting, and specific. Moreover, using a reporter assay,
      we show that antisense LNA/DNA oligonucleotides inhibit short non-coding RNAs at
      the functional level. Thus LNA/DNA mixmers represent powerful tools for
      functional analysis of miRNAs.

PMID- 16962737
TI  - L1210 cells cultivated under the selection pressure of doxorubicin or vincristine
      express common mechanisms of multidrug resistance based on the overexpression of
      P-glycoprotein.
AB  - Multidrug resistance of neoplastic tissue is often associated with the
      overexpression and increased drug transport activity of plasma membrane
      transporters like P-glycoprotein (P-gp), multidrug resistance associated proteins
      (MRPs) or breast cancer resistance protein, as well as with the elevation of the
      glutathione detoxification pathway. We have already described the overexpression
      of P-gp under the selection pressure of vincristine in L1210 mouse leukemia
      cells. In the present study, mechanisms of multidrug resistance induced in L1210
      cells cultivated in the presence of doxorubicin were analyzed. The selection
      pressure of both vincristine (yielding a resistant subline of L1210 cells, R(V))
      and doxorubicin (yielding a resistant subline of L1210 cells, R(D)) induced a
      dramatic depression of cell sensitivity to both drugs. Both R(V) and R(D) cells
      demonstrated a lack of ability to accumulate calcein/AM and fluo-3/AM as
      fluorescent substrates of P-gp and MRP. The retention of dyes could be reached in
      both cell sublines by the application of inhibitors of P-gp (like verapamil) but
      not by probenecid - an inhibitor of anion transporters, including MRPs. Massive
      protein bands, at a M(r) range of 130-180 kDa that interact with c219 antibody
      against P-gp, were detected in the crude membrane fraction isolated from both
      R(V) and R(D) (but not from L1210) cells by Western blot. The cytosolic activity
      of glutathione S-transferase was found to be similar in R(V) and R(D) cells and
      did not differ significantly from the activity ascertained in parental L1210
      cells. Neither the R(V) nor R(D) cell sublines differed considerably, as measured
      by cell ultrastructure. In conclusion, based on P-gp overexpression, both
      doxorubicin and vincristine induce a common multidrug resistance phenotype in
      L1210 cells.

PMID- 16962736
TI  - Sentinel node mapping and biopsy in thyroid cancer: a surgical perspective.
AB  - The clinical role of sentinel node biopsy (SNB) in thyroid cancer remains an open
      matter in literature. The main reason of this fact is that nodal disease is
      considered a non-relevant prognostic factor by some authors in differentiated
      thyroid cancer (DTC). Aim of this study was to investigate the efficacy of
      radiocolloid lymphoscintigraphy and of hand held gamma probe procedure for SNB in
      patients with DTC and its potential clinical role. Forty-one consecutive pts with
      a small thyroid nodule highly suspected for malignancy at fine-needle aspiration
      cytology (FNAC) and without clinical and ultrasonographic (US) evidence of lymph
      node involvement entered the study. All patients underwent lymphoscintigraphy 3
      hours before intervention using a 99mTc-nanocolloid solution. One single
      intratumoral injection of 4-9 MBq in 0.1-02 ml normal saline was obtained under
      US-guidance followed by a dynamic lymphoscintigraphy. After total thyroidectomy
      central and lateral compartments of the neck were scanned with a hand held gamma
      probe. The hottest node and any lymph node with a count rate of more than 10% of
      the hottest node were removed. SLNs were sent to frozen section analysis and a
      surgical enlargement of corresponding compartment was performed when at least one
      SLN was positive at histology. Preoperative lymphoscintigraphy was able to
      identify one node in six cases, two nodes in five cases, three nodes in 14 cases,
      four or more nodes in 16 cases. A papillary thyroid carcinoma (PTC) was diagnosed
      in 39 cases, a mixed papillary-medullary carcinoma in one case and a micro
      follicular adenoma in one case. In 21/40 patients (pts) positive lymph nodes were
      found: in 16/21 patient one node showed micrometastasis only, in 5/21 patients
      more nodes were metastatic. In particular in 11 cases the first hottest node was
      involved (true SLN), in 10 cases a second or third hot lymph node was involved.
      In our preliminary experience lymphoscintigraphy with 99mTc-nanocolloid resulted
      highly sensitive: in fact at least one lymph node was visualized in all cases and
      the surgeon was able to detect by means of hand held probe during intervention al
      least one hot SLN in all cases. In 21/40 pts (more than 50% of cases) metastatic
      lymph nodes were found despite preoperative clinical and US examination negative
      for lymph node involvement. In prospective SLN technique might be proposed as a
      relevant tool in lymphoadenectomy decision in DTC patients with a small tumor.

PMID- 16962738
TI  - DMRT gene cluster analysis in the platypus: new insights into genomic
      organization and regulatory regions.
AB  - We isolated and characterized a cluster of platypus DMRT genes and compared their
      arrangement, location, and sequence across vertebrates. The DMRT gene cluster on
      human 9p24.3 harbors, in order, DMRT1, DMRT3, and DMRT2, which share a DM domain.
      DMRT1 is highly conserved and involved in sexual development in vertebrates, and
      deletions in this region cause sex reversal in humans. Sequence comparisons of
      DMRT genes between species have been valuable in identifying exons, control
      regions, and conserved nongenic regions (CNGs). The addition of platypus
      sequences is expected to be particularly valuable, since monotremes fill a gap in
      the vertebrate genome coverage. We therefore isolated and fully sequenced
      platypus BAC clones containing DMRT3 and DMRT2 as well as DMRT1 and then
      generated multispecies alignments and ran prediction programs followed by
      experimental verification to annotate this gene cluster. We found that the three
      genes have 58-66% identity to their human orthologues, lie in the same order as
      in other vertebrates, and colocate on 1 of the 10 platypus sex chromosomes, X5.
      We also predict that optimal annotation of the newly sequenced platypus genome
      will be challenging. The analysis of platypus sequence revealed differences in
      structure and sequence of the DMRT gene cluster. Multispecies comparison was
      particularly effective for detecting CNGs, revealing several novel potential
      regulatory regions within DMRT3 and DMRT2 as well as DMRT1. RT-PCR indicated that
      platypus DMRT1 and DMRT3 are expressed specifically in the adult testis (and not
      ovary), but DMRT2 has a wider expression profile, as it does for other mammals.
      The platypus DMRT1 expression pattern, and its location on an X chromosome,
      suggests an involvement in monotreme sexual development.

PMID- 16962739
TI  - Gene expression profiling studies on Caenorhabditis elegans dystrophin mutants
      dys-1(cx-35) and dys-1(cx18).
AB  - The Caenorhabditis elegans genome contains a single dystrophin/utrophin
      orthologue, dys-1. Point mutations in this gene, dys-1(cx35) and dys-1(cx18),
      result in truncated proteins. Such mutants offer potentially valuable worm models
      of human Duchenne muscular dystrophy. We have used microarrays to examine genes
      expressed differentially between wild-type C. elegans and dys-1 mutants. We found
      106 genes (115 probe sets) to be differentially expressed when the two mutants
      are compared to wild-type worms, 49 of which have been assigned to six functional
      categories. The main categories of regulated genes in C. elegans are genes
      encoding intracellular signalling, cell-cell communication, cell-surface, and
      extracellular matrix proteins; genes in these same categories have been shown by
      others to be differentially expressed in muscle biopsies of muscular dystrophy
      patients. The C. elegans model may serve as a convenient vehicle for future
      genetic and chemical screens to search for new drug targets.

PMID- 16962740
TI  - Prenatal cocaine and morphine alter brain cyclin-dependent kinase 5 (Cdk5)
      activity in rat pups.
AB  - Pregnant rats received daily injections of saline, cocaine (20 mg/kg), morphine
      (2 mg/kg), or the combination of both drugs, on days 13-20 of gestation. Cyclin
      dependent kinase 5 (Cdk5) activity was then measured in the resulting pups on
      postnatal days 1, 7, 14 and 28. Cocaine resulted in a time dependent increase in
      brain Cdk5 activity which peaked on day 14. Morphine, in contrast, induced a
      decrease in Cdk5 activity which was also maximal on day 14. Combined
      administration of the two drugs led to smaller increases than those seen after
      cocaine alone. These findings demonstrate that prenatal drug exposure can modify
      postnatal activity of Cdk5 in the brain and raise the possibility that
      alterations in Cdk5 may play a role in some of the neural and behavioral effects
      produced by these treatments.

PMID- 16962741
TI  - Disc-repositioning surgery of the temporomandibular joint using bioresorbable
      screws.
AB  - For successful disc-repositioning surgery, following arthrotomy and disc recovery
      by the release of attachments, the disc must be fixed and stabilized in the
      correct relationship with the condyle and fossa. This report describes a new
      surgical technique for fixing the disc to the condyle using two resorbable
      screws.

PMID- 16962742
TI  - A population based elaboration of the role of age of onset on the course of
      schizophrenia.
AB  - BACKGROUND: Despite suggestions that an earlier age of onset and being male
      confer to a poorer course of schizophrenia, evidence regarding when these effects
      are most salient appears to be ambiguous. AIMS: To examine the relationship of
      age of first hospitalization and sex with the course of hospitalization in a
      population based cohort. METHOD: All first admissions for schizophrenia in a
      national population based cohort in Israel from 1978 to 1992 were followed
      through 1996 (n=12,071) using data from the National Psychiatric Hospitalization
      Case Registry of the State of Israel, a complete national registry of psychiatric
      admissions. Recursive partitioning was conducted to empirically determine cut-off
      points for age groups showing the greatest difference on the variables of
      interest. RESULTS: A younger age of first hospital admission was associated with
      a greater likelihood of having more than one hospital admission, longer first
      admissions, more hospital admissions and more inpatient days per year. Of
      patients with age of first admission below 17, 82.5% had more than one admission
      which decreased for subsequent age groups to 73.54% (18-28), 69.36% (29-31),
      62.88% (32-45), and 50.77% (over 45). Men had an earlier first admission than
      women, and had slightly more cut-off values. Irrespective of sex, the
      relationship between age at first admission and later hospitalization conformed
      to a linear trend. CONCLUSIONS: An earlier onset corresponds linearly with the
      severity of the course of illness and appears to have prognostic value.

PMID- 16962743
TI  - Effect of tea phenolics and their aromatic fecal bacterial metabolites on
      intestinal microbiota.
AB  - Tea is rich in polyphenols and other phenolics that have been widely reported to
      have beneficial health effects. However, dietary polyphenols are not completely
      absorbed from the gastrointestinal tract and are metabolized by the gut
      microflora so that they and their metabolites may accumulate to exert
      physiological effects. In this study, we investigated the influence of the
      phenolic components of a tea extract and their aromatic metabolites upon
      bacterial growth. Fecal homogenates containing bacteria significantly catalyzed
      tea phenolics, including epicatechin, catechin, 3-O-methyl gallic acid, gallic
      acid and caffeic acid to generate aromatic metabolites dependent on bacterial
      species. Different strains of intestinal bacteria had varying degrees of growth
      sensitivity to tea phenolics and metabolites. Growth of certain pathogenic
      bacteria such as Clostridium perfringens, Clostridium difficile and Bacteroides
      spp. was significantly repressed by tea phenolics and their derivatives, while
      commensal anaerobes like Clostridium spp., Bifidobacterium spp. and probiotics
      such as Lactobacillus sp. were less severely affected. This indicates that tea
      phenolics exert significant effects on the intestinal environment by modulation
      of the intestinal bacterial population, probably by acting as metabolic
      prebiotics. Our observations provide further evidence for the importance of
      colonic bacteria in the metabolism, absorption and potential activity of
      phenolics in human health and disease. The bioactivity of different phenolics may
      play an important role in the maintenance of gastrointestinal health.

PMID- 16962744
TI  - Resistance of surface-confined telomers with pendent glucosylurea groups against
      non-specific adsorption of proteins.
AB  - A disulfide-carrying random telomer with pendent D-glucosylurea groups (Cys
      poly(glucosylureaethyl methacrylate-r-ureaethyl methacrylate), Cys-Poly(GUMA-r
      UMA)) was obtained by UV-irradiation of GUMA and UMA in the presence of benzyl
      N,N-diethyldithiocarbamoyl (BDC) derivative which shows the abilities of
      initiation, transfer, and termination (iniferter). The disulfide-carrying telomer
      was accumulated on a gold electrode and colloidal gold-immobilized glass
      substrate, and the binding of various proteins to the surface of the polymer
      brush was examined by both cyclic voltammetry (CV) with hydroquinone as a probe,
      and localized surface plasmon resonance (LSPR) absorption method. The Cys
      Poly(GUMA-r-UMA) brush did not show a significant non-specific adsorption of
      proteins such as bovine serum albumin and egg white lysozyme. Furthermore, sugar
      binding proteins, concanavalin A (with an affinity for mannose and glucose) and
      wheat germ agglutinin (with an affinity for N-acetylglucosamine), were only
      slightly adsorbed to the GUMA-carrying brush, which is in contrast with the
      prompt and distinct binding of these proteins to the brushes composed of 2
      methacryloyloxyethyl D-glucopyranoside and 1-(6'-methacrylamido)hexyl-2-N
      acetoamido-2-deoxy-D-glucopyranoside, respectively. The glucosylurea group
      carrying telomer brush prepared here might be useful to provide a "bio-inert"
      surface in bio-medical fields.

PMID- 16962745
TI  - Biomimetics of silver nanoparticles by white rot fungus, Phaenerochaete
      chrysosporium.
AB  - Extracellular synthesis of silver nanoparticles by a white rot fungus,
      Phaenerochaete chrysosporium is reported in this paper. Incubation of P.
      chrysosporium mycelium with silver nitrate solution produced silver nanoparticles
      in 24h. These silver nanoparticles were characterized by means of UV-vis
      spectroscopy, X-ray diffraction analysis, scanning electron microscopy,
      transmission electron microscopy, and photoluminescence spectroscopy. The
      synthesized silver nanoparticles absorbed maximum at 470 nm in the visible
      region. XRD spectrum of the silver nanoparticles confirmed the formation of
      metallic silver. The SEM characterization of the fungus reacted on the Ag+
      indicated that the protein might be responsible for the stabilization of silver
      nanoparticles. This result was further supported by the TEM examination. Though
      shape variation was noticed, majority of the nanoparticles were found to be of
      pyramidal shape as seen under TEM. Photoluminescence spectrum showed a broad
      emission peak of silver nanoparticles at 423 nm when excited at 350 nm. Apart
      from eco-friendliness, fungus as bio-manufacturing unit will give us an added
      advantage in ease of handling when compared to other classes of microorganisms.

PMID- 16962746
TI  - [Child fever in tropical area: don't forget Borreliosis].

PMID- 16962747
TI  - How can information extraction ease formalizing treatment processes in clinical
      practice guidelines? A method and its evaluation.
AB  - OBJECTIVE: Formalizing clinical practice guidelines (CPGs) for a subsequent
      computer-supported processing is a challenging, but burdensome and time-consuming
      task. Existing methods and tools to support this task demand detailed medical
      knowledge, knowledge about the formal representations, and a manual modeling.
      Furthermore, formalized guideline documents mostly fall far short in terms of
      readability and understandability for the human domain modeler. METHODS AND
      MATERIAL: We propose a new multi-step approach using information extraction
      methods to support the human modeler by both automating parts of the modeling
      process and making the modeling process traceable and comprehensible. This paper
      addresses the first steps to obtain a representation containing processes which
      is independent of the final guideline representation language. RESULTS: We have
      developed and evaluated several heuristics without the need to apply natural
      language understanding and implemented them in a framework to apply them to
      several guidelines from the medical subject of otolaryngology. Findings in the
      evaluation indicate that using semi-automatic, step-wise information extraction
      methods are a valuable instrument to formalize CPGs. CONCLUSION: Our evaluation
      shows that a heuristic-based approach can achieve good results, especially for
      guidelines with a major portion of semi-structured text. It can be applied to
      guidelines irrespective to the final guideline representation format.

PMID- 16962748
TI  - Pharmaceutical and analytical characterisation of (2R)-(3-amino-2
      fluoropropyl)sulphinic acid, a GABAB receptor agonist.
AB  - (2R)-(3-amino-2-fluoropropyl)sulphinic acid (AFPSiA) is a potent GABAB agonist,
      which makes it a possible alternative in future GERD treatment. The degradation
      of AFPSiA was investigated to support the drug-development effort. The compound
      is too polar to be compatible with regular reversed-phase LC. Moreover, the
      compound and the degradation products cannot be detected by UV due to low
      absorption. Instead, the degradation of AFPSiA was followed by two different
      capillary electrophoresis methods with indirect UV detection and 1H NMR and 19F
      NMR. AFPSiA was very unstable in basic conditions and at temperatures above room
      temperature. The corresponding sulphonic acid and allylamine are formed via two
      separate degradation routes. Both these degradation products may cause unwanted
      side-effects in vivo. Aqueous solutions of AFPSiA were found to be more stable at
      pH between 1 and 3. It was suggested that AFPSiA should be stored frozen,
      preferably at -70 degrees C. In solid state, the compound can be stored at
      ambient conditions in closed vials with low relative humidity. A solid oral
      dosage form should be kept in a blister package.

PMID- 16962749
TI  - Solid lipid microparticles as a sustained release system for pulmonary drug
      delivery.
AB  - The controlled release of drugs for pulmonary delivery is a research field which
      has been so far rather unexploited but is currently becoming increasingly
      attractive. The introduction part of this research article first details the
      potential advantages of solid lipid microparticles (SLMs) as drug carrier
      compared to liposomes and polymeric microspheres. The aim of this work is to use
      SLMs to impart a sustained release profile to a model drug, salbutamol acetonide
      (SA). SA was synthesized from salbutamol in order to increase the lipophilicity
      of this molecule and thereby to increase its incorporation efficiency into SLMs.
      SA-loaded SLMs were then produced by a hot emulsion technique followed by high
      shear homogenisation and the manufacturing parameters were optimized using the
      experimental design methodology in order to reach a suitable particle size for
      pulmonary administration. Scanning electron micrographs showed that SLMs are
      spherical, have a smooth surface and that SA crystallizes outside of the
      particles when the drug loading is higher than 20%. This was confirmed by X-ray
      diffraction. SA in vitro release study from SLMs showed that the release rate
      increased with SA loading but remained in every case lower than the dissolution
      rate of pure SA.

PMID- 16962750
TI  - Studies on dissolution enhancement and mathematical modeling of drug release of a
      poorly water-soluble drug using water-soluble carriers.
AB  - Role of various water-soluble carriers was studied for dissolution enhancement of
      a poorly soluble model drug, rofecoxib, using solid dispersion approach. Diverse
      carriers viz. polyethylene glycols (PEG 4000 and 6000), polyglycolized fatty acid
      ester (Gelucire 44/14), polyvinylpyrollidone K25 (PVP), poloxamers (Lutrol F127
      and F68), polyols (mannitol, sorbitol), organic acid (citric acid) and
      hydrotropes (urea, nicotinamide) were investigated for the purpose. Phase
      solubility studies revealed AL type of curves for each carrier, indicating linear
      increase in drug solubility with carrier concentration. The sign and magnitude of
      the thermodynamic parameter, Gibbs free energy of transfer, indicated spontaneity
      of solubilization process. All the solid dispersions showed dissolution
      improvement vis-a-vis pure drug to varying degrees, with citric acid, PVP and
      poloxamers as the most promising carriers. Mathematical modeling of in vitro
      dissolution data indicated the best fitting with Korsemeyer-Peppas model and the
      drug release kinetics primarily as Fickian diffusion. Solid state
      characterization of the drug-poloxamer binary system using XRD, FTIR, DSC and SEM
      techniques revealed distinct loss of drug crystallinity in the formulation,
      ostensibly accounting for enhancement in dissolution rate.

PMID- 16962751
TI  - Nanoparticles based on N-trimethylchitosan: evaluation of absorption properties
      using in vitro (Caco-2 cells) and ex vivo (excised rat jejunum) models.
AB  - Among the chitosan derivatives, trimethylchitosan (TMC) has been shown to have
      penetration enhancement properties also in intestinal environment. In addition,
      the use of nanoparticulate systems has the advantage of protecting peptidic drugs
      from intestinal degradations, due to internalisation behaviour. Therefore, the
      aim of this paper was to evaluate nanoparticulate systems based on TMC. In
      particular the mucoadhesive and absorption enhancement properties of
      nanoparticles based on TMC with different quaternization degree (QD) intended for
      the intestinal administration of macromolecules (peptides) have been evaluated.
      Comparison with chitosan (CS.HCl) nanoparticles was made. The nanoparticles were
      loaded with fluorescein isothiocyanate dextran (FD4, MW 4400 Da), used as the
      model macromolecule. The intestinal penetration enhancement properties of
      nanoparticles were investigated in an in vitro Caco-2 cell model and an ex vivo
      rat jejunum model. The mucoadhesion of the nanosystems was evaluated using
      excised rat jejunum. All of the nanoparticulate systems interacted with the Caco
      2 cells decreasing the transepithelial electric resistance (TEER) and increasing
      Lucifer Yellow (LY) Papp (paracellular pathway marker). All the nanosystems
      improved FD4 Papp, with the exception of the nanoparticles based on TMC with the
      highest QD. In this case an entrapment of nanoparticles into Caco-2 cells was
      supposed. Analogous results were obtained using the excised rat jejunum model.
      The increase in QD of TMC was seen to favour the mucoadhesion, resulting in a
      prolonged residence time on intestinal mucosa. The nanoparticle penetration into
      excised rat jejunum tissue, observed by means of CLSM, suggested that the
      mucoadhesive properties delayed the absorption of nanoparticles, however they
      produced an increase in the contact time with intestinal epithelium, offering a
      better chance for internalisation. The improvement of mucoadhesion and of
      nanoparticle internalisation with respect to chitosan nanosystems makes the TMCs
      nanosystems suitable carriers for the intestinal absorption of peptides.

PMID- 16962752
TI  - The effects of capture spiral composition and orb-web orientation on prey
      interception.
AB  - Cribellar prey capture threads found in primitive, horizontal orb-webs reflect
      more light, including ultraviolet wavelengths, than viscous threads found in more
      derived, vertical orb-webs. Low web visibility and vertical orientation are each
      thought to increase prey interception and may represent key innovations that
      contributed to the greater diversity of modern, araneoid orb-weaving spiders.
      This study compares prey interception rates of cribellate orb-webs constructed by
      Uloborus glomosus (Uloboridae) with viscous orb-webs constructed by Leucauge
      venusta (Tetragnathidae) and Micrathena gracilis (Araneidae). We placed sectors
      of cribellar and viscous threads side by side in frames that were oriented either
      horizontally or vertically. The webs of both U. glomosus and L. venusta
      intercepted more prey when vertically oriented. In each orientation L. venusta
      webs intercepted more insects than did U. glomosus. Although this is consistent
      with the greater visibility of cribellar threads, the more closely spaced capture
      spirals of L. venusta may have contributed to this difference. Micrathena
      gracilis webs intercepted more prey than did U. glomosus webs, although web
      orientation did not affect the performance of this araneoid species. The stickier
      and more closely spaced capture spirals of M. gracilis may have enhanced the
      interception rates of this species and accounted for the greater number of
      smaller dipterans retained in its webs. The tendency for these slow, weak flight
      insects to be blown into both horizontal and vertical webs may account for
      similar interception rates of horizontal and vertical M. gracilis webs. These
      observations support the enhanced prey interception of vertically oriented orb
      webs, but offer only qualified support for the contributions of lower visibility
      viscous capture threads.

PMID- 16962753
TI  - Siderophore cross-utilization amongst nodule isolates of the cowpea miscellany
      group and its effect on plant growth in the presence of antagonistic organisms.
AB  - Nodule isolates from the cowpea miscellany group of legumes produced varying
      concentrations of catecholate and hydroxamate types of siderophores under iron
      limiting conditions. The nodule isolates differed with respect to siderophore
      cross-utilizing abilities; some were proficient at using siderophores of other
      nodule isolates (homologous siderophores) while others could utilize siderophores
      produced by other rhizospheric bacteria (heterologous siderophores). Utilization
      of siderophore of rhizospheric bacterium PsB, a plant pathogen, benefited the
      nodule isolate G11 in terms of growth under iron-limiting laboratory conditions,
      while PsB was clearly inhibited in the presence of G11. Plate assays showed that
      siderophore of G11 could withhold iron from PsB and hence PsB was inhibited in
      the presence of G11. Isolates G11 and PsB when applied simultaneously to peanut
      seedlings under sterile soil conditions, provided a clear advantage to the plant
      in terms of reduction in the inhibitory effect of PsB. The count of the nodule
      isolate G11 increased in the soil when co-inoculated with PsB, as compared to
      when inoculated alone. Thus, the increased growth of the plant can be attributed
      to the iron sequestration and plant growth promoting properties of G11. The
      isolate G11 could utilize the siderophores produced by many other rhizospheric
      isolates while the siderophore of G11 was not being utilized by these
      rhizospheric isolates.

PMID- 16962754
TI  - Biological and physiological characteristics of Neotyphodium gansuense symbiotic
      with Achnatherum inebrians.
AB  - Biological and physiological characteristics of Neotyphodium gansuense were
      compared with Neotyphodium coenophialum and Epichloe festucae at a range of
      temperatures and pH values, and on carbon and nitrogen amended media. N.
      gansuense was able to grow at 10-30 degrees C, but not at 5 degrees C, and slowly
      at 35 degrees C. The optimal temperature for both N. gansuense and N.
      coenophialum was 25 degrees C, but that of E. festucae was 20-25 degrees C. The
      optimal pH ranges for mycelial growth of N. gansuense, N. coenophialum and E.
      festucae were 5-9, 5-9 and 5-7, respectively. The Neotyphodium and Epichloe
      endophytes varied in their ability to grow on media containing different carbon
      and nitrogen nutrients. The preference of N. gansuense for carbon source was
      sucrose>glucose, lactose, sorbitol, inulin, maltose, mannitol, starch,
      fructose>xylose. Growth of all three endophytes tested was significantly improved
      by peptone, tryptone, casein, yeast extract and l-proline. Yeast extract,
      peptone, casein, tryptone, l-proline, potassium nitrate, ammonium oxalic acid and
      l-leucine significantly improved growth of N. gansuense. However, ammonium
      nitrite was not utilized at all by any tested endophyte. N. gansuense grew
      significantly better on potato dextrose agar (PDA) and oat meal agar (OMA) than
      on corn meal agar (CMA) and drunken-horse-grass agar (DA), and most slowly on
      water agar (WA) and saltwater nutrient agar (SNA).

PMID- 16962755
TI  - In vitro antifungal susceptibility of clinical isolates of Candida spp. obtained
      from patients with different predisposing factors to candidosis.
AB  - The increase in the number of infections caused by Candida species and the
      consequent use of antifungal agents favours an increase of resistant isolates.
      The aim of this study was to evaluate the antifungal susceptibility of Candida
      spp. isolates from patients with different systemic predisposing factors to
      candidosis. Seventy-nine Candida spp. isolates were assayed for in vitro
      susceptibility to amphotericin B, fluconazole, 5-flucytosine and itraconazole
      using the technique proposed by the Clinical and Laboratory Standards Institute
      (CLSI). Four C. albicans, one C. guilliermondii, four C. parapsilosis and two C.
      tropicalis isolates were resistant to amphotericin B. Only two isolate was
      resistant to itraconazole. All the isolates tested were susceptible to
      fluconazole and flucytosine. It could be concluded that the most efficient drugs
      against the Candida isolates studied were fluconazole and flucytosine and that
      all of the antifungal agents used in this study were effective against the
      Candida spp. isolates tested.

PMID- 16962756
TI  - Characterization of fibroblast morphology on bioactive surfaces using vertical
      scanning interferometry.
AB  - Tissue donor scarcity is a major hindrance to articular cartilage tissue
      engineering. Previous research shows that dermal fibroblasts express chondrocytic
      markers after seeding on aggrecan-coated surfaces. Since cell roundness appears
      to correlate with chondrocytic behavior of dermal fibroblasts, this study
      quantified roundness by measuring cell height and surface area-volume ratio. In
      addition to aggrecan as a surface coating, collagen type II and decorin, two
      other major extracellular matrix components of articular cartilage, were
      examined. Aggrecan, collagen type II, and decorin were coated onto a glass
      substrate using three application techniques: static drying, airbrush, and
      painting. Vertical scanning interferometry (VSI) is a novel technique that allows
      for the expedient morphological determination of single cells. Interferometry was
      used for the characterization of protein-coated surfaces in addition to
      characterizing the morphology of single dermal fibroblasts after 24 h of seeding.
      Fibroblast height was found to vary from 1.0 to 4.0 microm and protein coating,
      application technique, and seeding position were significant factors (p < 0.002).
      The largest cell heights were observed on aggrecan and collagen type II coated
      surfaces using the air brush and static applications. Additionally, variations
      were observed for surface area-volume ratio, ranging from 1.75 to 11.94 microm(
      1) with decorin resulting in the lowest ratio, followed by collagen type II and
      aggrecan. This study identifies optimal coating conditions for stimulating
      morphology in dermal fibroblasts that is characteristic of the chondrocytic
      phenotype. These conditions can be employed to attempt articular cartilage
      regeneration and bypass difficulties due to a paucity of donor tissue.

PMID- 16962757
TI  - Omega-3 fatty acid status in attention-deficit/hyperactivity disorder.
AB  - Lower levels of long-chain polyunsaturated fatty acids, particularly omega-3
      fatty acids, in blood have repeatedly been associated with a variety of
      behavioral disorders including attention-deficit/hyperactivity disorder (ADHD).
      The exact nature of this relationship is not yet clear. We have studied children
      with ADHD who exhibited skin and thirst symptoms classically associated with
      essential fatty acid (EFA) deficiency, altered plasma and red blood cell fatty
      acid profiles, and dietary intake patterns that do not differ significantly from
      controls. This led us to focus on a potential metabolic insufficiency as the
      cause for the altered fatty acid phenotype. Here we review previous work and
      present new data expanding our observations into the young adult population. The
      frequency of thirst and skin symptoms was greater in newly diagnosed individuals
      with ADHD (n = 35) versus control individuals without behavioral problems (n =
      112) drawn from the Purdue student population. A follow up case-control study
      with participants willing to provide a blood sample, a urine sample, a
      questionnaire about their general health, and dietary intake records was
      conducted with balancing based on gender, age, body mass index, smoking and
      ethnicity. A number of biochemical measures were analyzed including status
      markers for several nutrients and antioxidants, markers of oxidative stress,
      inflammation markers, and fatty acid profiles in the blood. The proportion of
      omega-3 fatty acids was found to be significantly lower in plasma phospholipids
      and erythrocytes in the ADHD group versus controls whereas saturated fatty acid
      proportions were higher. Intake of saturated fat was 30% higher in the ADHD
      group, but intake of all other nutrients was not different. Surprisingly, no
      evidence of elevated oxidative stress was found based on analysis of blood and
      urine samples. Indeed, serum ferritin, magnesium, and ascorbate concentrations
      were higher in the ADHD group, but iron, zinc, and vitamin B6 were not different.
      Our brief survey of biochemical and nutritional parameters did not give us any
      insight into the etiology of lower omega-3 fatty acids, but considering the
      consistency of the observation in multiple ADHD populations continued research in
      this field is encouraged.

PMID- 16962758
TI  - Dyspnoea at 6-min walk test in idiopathic pulmonary fibrosis: comparison with
      COPD.
AB  - The characteristics of dyspnoea in idiopathic pulmonary fibrosis (IPF) during a 6
      min walk test are not clear. This study was designed to evaluate dyspnoea and
      desaturation during the 6-min walk test in IPF in comparison with that in chronic
      obstructive pulmonary disease (COPD), which is one of the most studied chronic
      lung diseases. The 41 consecutive patients with IPF included in this study were
      assessed by a 6-min walk test and concurrent measures of disease severity. Forty
      one age-matched and resting PaO(2) value-matched COPD patients who had undertaken
      the test during the same period were selected as the control. Only O(2)
      saturation at the end of the test was an independent predictor of dyspnoea in IPF
      (r(2)=0.27, P=0.0005), whereas forced expiratory volume in 1s (FEV(1)) was the
      only predictor in COPD (r(2)=0.16, P=0.0096). Desaturation was significantly more
      severe in IPF (83.6+/-9.1% in IPF versus 88.0+/-5.9% in COPD, P<0.001). In
      contrast, dyspnoea assessed with the Borg scale was significantly more severe in
      COPD (3.6+/-2.1 in IPF versus 4.6+/-1.9 in COPD, P<0.05). O(2) saturation is an
      independent predictor of dyspnoea at the end of a 6-min walk test in IPF. In
      comparison with COPD, desaturation is more severe, although dyspnoea is milder.

PMID- 16962759
TI  - beta-amyloid or its precursor protein is found in epithelial cells of the small
      intestine and is stimulated by high-fat feeding.
AB  - In Alzheimer's disease (AD), beta-amyloid (Abeta) is deposited in extracellular
      matrices, initiating an inflammatory response and compromising cellular
      integrity. Epidemiological evidence and studies in animal models provide strong
      evidence that high-saturated-fat and/or cholesterol-rich diets exacerbate
      cerebral amyloidosis, although the mechanisms for this are unclear. Abeta
      contains hydrophobic domains and is normally bound to lipid-associated chaperone
      proteins. In previous studies, we have put forward the notion that Abeta is a
      regulatory component of postprandial lipoproteins (i.e., chylomicrons) and that
      aberrations in kinetics may be a contributing risk factor for AD. To explore this
      further, in this study, we utilized an immunohistochemical approach to determine
      if Abeta or its precursor protein is expressed in epithelial cells of the small
      intestine -- the site of chylomicron biogenesis. Wild-type mice were fed a low
      fat or a high-fat dietary regime and sacrificed, and their small intestines were
      isolated. We found that, in mice fed low-fat chow, substantial Abeta/precursor
      protein was found exclusively in absorptive epithelial cells of the small
      intestine. In contrast, no Abeta/precursor protein was found in epithelial cells
      when mice were fasted for 65 h. In addition, we found that a high-fat feeding
      regime strongly stimulates epithelial cell Abeta/precursor protein concentration.
      Our findings are consistent with the notion that Abeta may serve as a regulatory
      apolipoprotein of postprandial lipoproteins.

PMID- 16962760
TI  - Isoflavone-poor soy protein alters the lipid metabolism of rats by SREBP-mediated
      down-regulation of hepatic genes.
AB  - Soy intake acts hypolipidemically. Besides isoflavones, soy protein itself is
      suggested to influence plasma lipid concentrations. We investigated the effects
      of an alcohol-washed isoflavone-poor soy protein isolate on plasma and liver
      lipids and the hepatic expression of genes encoding proteins involved in
      cholesterol and fatty acid metabolism. Therefore, rats were fed diets containing
      200 g/kg of either ethanol-extracted soy protein isolate or casein over 22 days.
      Rats fed soy protein isolate had markedly lower concentrations of liver
      cholesterol and lower concentrations of triglycerides in the liver and in plasma
      than rats fed casein (P<.05). Rats fed soy protein isolate had lower relative
      mRNA concentrations of sterol-regulatory element-binding protein (SREBP)-2, 3
      hydroxy-3-methylglutaryl coenzyme A reductase, low-density lipoprotein receptor,
      cholesterol 7alpha-hydroxylase, apolipoprotein B, Delta9-desaturase and glucose-6
      phosphate dehydrogenase in the liver than rats fed casein (P<.05). Hepatic mRNA
      concentration of SREBP-1c tended to be lower in rats fed soy protein isolate
      (P<.10). Hepatic mRNA concentrations of insulin-induced gene (Insig) 1 and Insig
      2 and of microsomal triglyceride transfer protein, as well as plasma
      concentrations of free fatty acids, insulin and glucagon, were not different
      between the two groups. In conclusion, this study suggests that isoflavone-poor
      soy protein isolate affects cellular lipid homeostasis by the down-regulation of
      SREBPs and its target genes in the liver, which are involved in the synthesis of
      cholesterol and triglycerides.

PMID- 16962761
TI  - Amperometric detection of bilirubin from a micro-sensing electrode with a
      synthetic bilirubin imprinted poly(MAA-co-EGDMA) film.
AB  - Poly(methacrylic acid-co-ethyl glycol dimethylacrylate) (poly(MAA-co-EGDMA))
      imprinted with alpha-bilirubin was shown to be able to bind alpha-bilirubin in
      our previous work. In this work, the corresponding imprinted polymer thin film
      was synthesized onto a thiol treated Au electrode by surface grafting
      polymerization. Bilirubin was able to be detected by an Au electrode, however,
      the electrode was not be able to discriminate bilirubin from the other matrix
      components if clinical samples were used. Therefore, the imprinted material was
      introduced so that the modified Au electrode could specifically detect bilirubin.
      Optimal potential was found to be 0.55 V and this was set for the rest of
      experiments. The imprinting factor of 3.16 was confirmed by comparing the signals
      from the MIP-Au and the NIP (non-imprinted polymer)-Au electrode. Calibration of
      the bilirubin concentration with respect to the current by the MIP-Au electrode
      was made within the range of 5mg/dl and a detection sensitivity of 0.644
      microA/mg/dl (2.58 microA/cm(2)/mg/dl) was obtained. Furthermore, a linear
      correlation of the bilirubin concentration within 1.0mg/dl versus detection
      current was also achieved. Bilirubin was further detected by the MIP-Au electrode
      in the presence of fetal bovine serum (FBS). Repeated detection of bilirubin with
      at least three detection batches was performed and the reproducibility of the
      same piece of MIP-Au electrode was confirmed. The result was compared to those
      obtained from the serum and the solvent solution. The results indicated the
      feasibility of using the bilirubin imprinted poly(MAA-co-EGDMA) film as a sensing
      electrode for the clinical detection of bilirubin in serum.

PMID- 16962762
TI  - A portable potentiostat for the bilirubin-specific sensor prepared from molecular
      imprinting.
AB  - A portable amperometric potentiostat was designed and implemented in this work.
      It was developed to acquisit the current signals produced from bilirubin by an
      electrochemical sensor. Based on an SOC-based chip, this potentiostat has the
      merits of moderate accuracy, small size, low cost, and high portability. The
      bilirubin electrode was prepared by synthesizing a thin layer of bilirubin
      imprinted poly(methacrylic acid-co-ethylene glycol dimethacrylate) onto the Au
      layer. With the molecularly imprinted polymer (MIP) film, specific detection of
      bilirubin was successfully achieved. The cyclic voltammogram of the electrode was
      measured from this assembled potentiostat. The performance from a commercial
      potentiostat was considered rather stable and was used as a reference to examine
      and evaluate the performance of the assembled potentiostat. The detected current
      signals by the bilirubin sensing were obtained. Linear calibration with a
      sensitivity of 1.344+/-0.38 microA/mg dl was achieved. Our experimental results
      showed that the proposed potentiostat's performance could achieve sufficient
      performance. The evaluation was also made from the aspects such as reset time and
      steady-response time. The self-assembled potentiostat thus demonstrated its
      ability in precise detection of bilirubin from an electrode layered with the
      imprinted polymer film.

PMID- 16962763
TI  - A miniaturized germanium-doped silicon dioxide-based surface plasmon resonance
      waveguide sensor for immunoassay detection.
AB  - A surface plasmon resonance (SPR) waveguide immunosensor fabricated by germanium
      doped silicon dioxide was investigated in this study. The designed waveguide
      sensor consisted of a 10 microm SiO(2) substrate layer (n=1.469), a 10 microm Ge
      SiO(2) channel guide (n=1.492) and a 50 nm gold film layer for immobilization of
      biomolecules and SPR signal detection. The resultant spectral signal was measured
      by a portable spectrophotometer, where the sensor was aligned by a custom
      designed micro-positioner. The results of the glycerol calibration standards
      showed that the resonance wavelength shifted from 628 to 758 nm due to changes of
      refractive index from 1.36 to 1.418. Flow-through immunoassay on waveguide
      sensors also showed the interactions of protein A, monoclonal antibody (mAb ALV
      J) and avian leucosis virus (ALVs) resulted in wavelength shifting of 4.17, 3.03
      and 2.18 nm, respectively. The SPR dynamic interaction could also be demonstrated
      successfully in 4 min as the sensor was integrated with a lateral flow
      nitrocellulose strip. These results suggest that SPR detection could be carried
      out on designed waveguide sensor, and the integration of nitrocellulose strip for
      sample filtering and fluid carrier would facilitate applications in point-of-care
      portable system.

PMID- 16962764
TI  - Accommodating space, time and randomness in network simulation.
AB  - Interest in the possibility of dynamically simulating complex cellular processes
      has escalated markedly in recent years. This interest has been fuelled by three
      factors: the generally accepted value in understanding living processes as
      integrated systems; the dramatic increase in computational capability; and the
      availability of new or improved technology for making the quantitative
      measurements that are needed to drive and validate cellular simulations. Between
      the extremes of atom-scale and organism-scale simulation is a vast middle-ground
      requiring simulation strategies that are capable of dealing with a range of
      spatial, temporal and molecular abundance scales that are crucial for a
      comprehensive understanding of integrative cell biology. Although at an early
      stage, methodological improvements and the development of computational platforms
      provide some hope that simulations will emerge that can bridge the gap between
      network models and the true operation of the cell as a complex machine.

PMID- 16962765
TI  - Evolutionary systems biology: links between gene evolution and function.
AB  - The recent accumulation of genome-wide data on various facets of gene expression,
      function and evolution stimulated the emergence of a new field, evolutionary
      systems biology. Many significant correlations were detected between variables
      that characterize the functioning of a gene, such as expression level, knockout
      effect, connectivity of genetic and protein-protein interaction networks, and
      variables that describe gene evolution, such as sequence evolution rate and
      propensity for gene loss. The first attempts on multidimensional analysis of
      genomic data yielded composite variables that describe the 'status' of a gene in
      the genomic community. However, it remains uncertain whether different functional
      variables affect gene evolution synergistically or there is a single, dominant
      factor. The number of translation events, linked to selection for translational
      robustness, was proposed as a candidate for such a major determinant of protein
      evolution. These developments show that, although the methodological basis of
      evolutionary systems biology is not yet fully solidified, this area of research
      is already starting to yield fundamental biological insights.

PMID- 16962766
TI  - Experimental approaches to identify genetic networks.
AB  - Systems biology offers the promise of a fully integrated view of cellular
      physiology. To realize this potential requires the analysis of diverse genome
      wide datasets and the incorporation of these analyses into integrated networks.
      In the past decade, the budding yeast Saccharomyces cerevisiae has provided the
      benchmark for the design of such large-scale experiments. Many of these
      experimental approaches have been adopted and adapted to study other systems,
      including worm, fly, fish and mammalian cultured cells, using an ingenious set of
      molecular tools.

PMID- 16962767
TI  - Towards neural circuit reconstruction with volume electron microscopy techniques.
AB  - Electron microscopy is the only currently available technique with a resolution
      adequate to identify and follow every axon and dendrite in dense neuropil.
      Reconstructions of large volumes of neural tissue, necessary to reconstruct even
      local neural circuits, have, however, been inhibited by the daunting task of
      serially sectioning and reconstructing thousands of sections. Recent
      technological developments have improved the quality of volume electron
      microscopy data and automated its acquisition. This opens up the prospect of
      reconstructing almost complete invertebrate and sizable fractions of vertebrate
      nervous systems. Such reconstructions of complete neural wiring diagrams could
      rekindle the tradition of relating neural function to the underlying
      neuroanatomical circuitry.

PMID- 16962768
TI  - Synaptic communication between neurons and NG2+ cells.
AB  - Chemical synaptic transmission provides the basis for much of the rapid signaling
      that occurs within neuronal networks. However, recent studies have provided
      compelling evidence that synapses are not used exclusively for communication
      between neurons. Physiological and anatomical studies indicate that a distinct
      class of glia known as NG2(+) cells also forms direct synaptic junctions with
      both glutamatergic and GABAergic neurons. Glutamatergic signaling can influence
      intracellular Ca(2+) levels in NG2(+) cells by activating Ca(2+) permeable AMPA
      receptors, and these inputs can be potentiated through high frequency
      stimulation. Although the significance of this highly differentiated form of
      communication remains to be established, these neuro-glia synapses might enable
      neurons to influence rapidly the behavior of this ubiquitous class of glial
      progenitors.

PMID- 16962769
TI  - New methods and uses for fast optical scanning.
AB  - Advanced optical imaging techniques used in neurobiology commonly employ
      fluorescent molecules for studying the structure and function of neural tissue.
      To obtain adequate spatio-temporal resolution, sophisticated scanning schemes are
      used to manage the excitation light going to and emission light coming from
      objects under observation. Although the fundamental principles of these
      techniques remain the same, such as scanning point illumination and point
      detection for confocal imaging, their physical implementation is the subject of
      technological advance, for example, the advent of inertia-free discontinuous
      scanning schemes. In general, the aims of these technological advances are to
      improve the spatio-temporal resolution of and/or reduce potential photodamage
      caused by optical imaging in live neural tissue. The number of recent advances in
      scanning methods indicates their increasing importance in imaging techniques.

PMID- 16962770
TI  - Reduced folate carrier gene G80A polymorphism is associated with an increased
      risk of gastroesophageal cancers in a Chinese population.
AB  - Low folate intake has been associated with an increased risk of both oesophageal
      and gastric cancers. Reduced folate carrier (RFC1, also named SLC19A1) is an
      essential folate transporter and functions as a bidirectional anion exchanger,
      taking up folate cofactors and exporting various organic anions. A G80A
      polymorphism in RFC1 gene has been shown to be associated with alterations in
      folate and homocysteine metabolism in healthy individuals. In this study, we
      hypothesised that genetic variants in RFC1 may modulate risk of oesophageal
      cancer (EC) and gastric cancer (GC). To test this hypothesis, we evaluated the
      associations of the G80A polymorphism of RFC1 with EC and GC risk in a case
      control study of 216 EC and 633 GC cases and 673 cancer-free controls in a
      Chinese population. We found that compared with the 80GG/GA genotypes in the
      recessive model, the variant homozygote RFC1 80AA was associated with a
      significantly increased risk of EC (adjusted odds ratio (OR)=1.80, 95% confidence
      interval (CI)=1.29-2.51), GC (adjusted OR=1.59, 95% CI=1.25-2.02) and EC and GC
      combined (adjusted OR=1.63, 95% CI=1.30-2.04). In the dominant model, the risk
      associated with RFC1 80AA was also elevated in EC (OR=1.35, 95% CI=0.91-1.99), GC
      (OR=1.43, 95% CI=1.07-1.91) and EC and GC combined (adjusted OR=1.40, 95% CI=1.07
      1.83), compared with the 80GG genotype. The stratification analyses showed that
      effects of the RFC1 80AA genotype were more evident in subgroups of relatively
      older (60 years), female, non-smokers, and non-drinkers both in EC and GC.
      Although the exact biological mechanism of this association remains to be
      explored, our findings suggest possible involvement of RFC1 variant in the
      susceptibility of EC and GC. Further large and functional studies are needed to
      confirm our findings.

PMID- 16962771
TI  - Optimization of phycocyanin extraction from Spirulina platensis using factorial
      design.
AB  - Phycocyanin extraction from cyanobacteria Spirulina platensis was optimized using
      factorial design and response surface techniques. The effects of temperature and
      biomass-solvent ratio on phycocyanin concentration and extract purity were
      evaluated to determine the optimum conditions for phycocyanin extraction. The
      optimum conditions for the extraction of phycocyanin from S. platensis were the
      highest biomass-solvent ratio, 0.08 gmL(-1), and 25 degrees C. Under these
      conditions it's possible to obtain an extract of phycocyanin with a concentration
      of 3.68 mgmL(-1) and purity ratio (A(615)/A(280)) of 0.46.

PMID- 16962772
TI  - A novel series of imidazo[1,2-a]pyridine derivatives as HIF-1alpha prolyl
      hydroxylase inhibitors.
AB  - Utilizing modeling information from a recently resolved structure of human HIF
      1alpha prolyl hydroxylase (EGLN1) and structure-based design, a novel series of
      imidazo[1,2-a]pyridine derivatives was prepared. The activity of these compounds
      was determined in a human EGLN1 assay and a limited SAR was developed.

PMID- 16962773
TI  - Design, synthesis, and characterization of new embelin derivatives as potent
      inhibitors of X-linked inhibitor of apoptosis protein.
AB  - X-Linked inhibitor of apoptosis protein (XIAP) is a promising molecular target
      for the design of new anticancer drugs aiming at promoting apoptosis in cancer
      cells. We have previously identified embelin as an inhibitor of XIAP through
      computational structure-based database screening. Herein, we report the design,
      synthesis, and evaluation of new embelin analogues as inhibitors of XIAP. Our
      efforts led to the identification of new and more potent inhibitors. For example,
      compound 6g has a Ki value of 180 nM binding to XIAP BIR3, in a competitive
      binding assay and represents a promising lead compound for further optimization.

PMID- 16962774
TI  - Fluorinated and hemifluorinated surfactants derived from maltose: synthesis and
      application to handling membrane proteins in aqueous solution.
AB  - Two novel fluorinated surfactants have been obtained by grafting by radical
      reaction either a fluorocarbon or an ethyl end-capped fluorocarbon chain onto the
      double bond of beta-D-allyl maltose. The two compounds thus obtained form
      polydisperse aggregates in water. They can keep membrane proteins water-soluble,
      but the protein/surfactant complexes are polydisperse, which affects neither the
      native state nor the stability of the proteins.

PMID- 16962775
TI  - Separation of anti-angiogenic and cytotoxic activities of borrelidin by
      modification at the C17 side chain.
AB  - A set of novel borrelidin analogues have been prepared by precursor-directed
      biosynthesis. Structure-activity relationship analysis suggests that steric
      structural arrangement within the C17 side chain is important for differentiating
      cytotoxic and anti-angiogenic activities. A C17-cyclobutyl analogue 3 was found
      to have markedly increased selectivity for in vitro angiogenesis inhibition over
      cytotoxicity and is therefore potentially useful as an anticancer agent.

PMID- 16962776
TI  - The role of clathrin-dependent endocytosis in bacterial internalization.
AB  - Internalization of bacteria into mammalian host cells has been studied
      extensively in the past two decades. These studies have highlighted the amazingly
      diverse strategies used by bacterial pathogens to induce their entry in non
      phagocytic cells. The roles of actin and of the whole cytoskeletal machinery have
      been investigated in great detail for several invasive organisms, such as
      Salmonella, Shigella, Yersinia and Listeria. Recent results using Listeria
      highlight a role for the endocytosis machinery in bacterial entry, suggesting
      that clathrin-dependent endocytic mechanisms are also involved in internalization
      of large particles. This contrasts with the generally accepted dogma but agrees
      with previous studies of bacterial and viral infections and also of phagocytosis.

PMID- 16962777
TI  - Focus on membrane dynamics.

PMID- 16962778
TI  - Biophysical properties of lipids and dynamic membranes.
AB  - The lipid bilayer is a 3D assembly with a rich variety of physical features that
      modulate cell signaling and protein function. Lateral and transverse forces
      within the membrane are significant and change rapidly as the membrane is bent or
      stretched and as new constituents are added, removed or chemically modified.
      Recent studies have revealed how differences in structure between the two
      leaflets of the bilayer and between different areas of the bilayer can interact
      together with membrane deformation to alter the activities of transmembrane
      channels and peripheral membrane binding proteins. Here, we highlight some recent
      reports that the physical properties of the membrane can help control the
      function of transmembrane proteins and the motor-dependent elongation of internal
      organelles, such as the endoplasmic reticulum.

PMID- 16962780
TI  - Unloading reaction to electrical stimulation at neutral and supinated ankle
      positions.
AB  - An unloading reaction has been characterized as a modified flexor reflex (FR), in
      which the standing subjects decrease the load on the stimulated foot and increase
      the load on the contralateral side, but, without withdrawal of the stimulated
      foot. Different behavioral circumstances have been shown to modulate this reflex.
      It is not known whether unloading reactions can be modulated with a loaded
      supinated ankle position, which, in excess, may result in an ankle sprain injury.
      Since ankle sprain depends on the load applied to a supinated foot, our premise
      is that unloading reactions may protect the ankle from a sprain injury.
      Therefore, this study investigated how the unloading reactions were modulated
      during a loaded supinated ankle condition. We delivered non-nociceptive and
      nociceptive electrical stimulations on the lateral aspect of the ankle in
      standing subjects with the foot in neutral and in a supinated position. The
      magnitude and latencies of reflex responses were registered using kinetic and
      kinematic analyses and subsequently compared among the conditions. The analysis
      demonstrated greater reactions for the supinated ankle condition. The individuals
      also moved their whole body downwards and shifted the body weight to the non
      stimulated foot. Therefore, this study suggested that a modified type of the
      classic flexion reflex, i.e., unloading reaction, may be used as a strategy to
      unload a supinated ankle and potentially minimize the risk of ankle sprain
      injuries.

PMID- 16962781
TI  - Reliability of the three-dimensional pendulum test for able-bodied children and
      children diagnosed with cerebral palsy.
AB  - This prospective study compared the test-retest reliability of thirteen variables
      calculated from the pendulum test in able-bodied children to those of children
      diagnosed with cerebral palsy. Ten healthy children and 10 children with a
      primary diagnosis of cerebral palsy (CP) (mean age 13 years) participated in the
      study. Data were collected using a three-dimensional motion analysis system on
      two separate occasions 73+/-28 days apart. The between day reliability ICC scores
      of all variables were moderate to very high (0.60-0.98) for children with CP and
      high to very high (0.71-0.98) for able-bodied children. The children with CP
      demonstrated slower maximum angular velocity compared to the able-bodied children
      (202 degrees /s versus 293 degrees /s, p<0.01). The time to maximum angular
      velocity occurred sooner for children with CP compared to able-bodied children
      (0.22s versus 0.34s, p<0.001). For some children with CP, the knee motions
      demonstrated were not oscillations of decreasing magnitude. Therefore the
      integrals of knee motion in each plane were calculated. For both groups of
      subjects the largest integrals of motion were in the sagittal plane (knee
      flexion/extension). The able-bodied subject's integrals were twice as large
      compared to subjects diagnosed with CP (p<0.01). High test-retest reliability of
      the variables suggests that the pendulum test provides an objective and reliable
      method to assess quadriceps spasticity in children with cerebral palsy.

PMID- 16962782
TI  - Structure-activity relationship for inhibition of 5alpha-reductase by
      triterpenoids isolated from Ganoderma lucidum.
AB  - In humans, 5alpha-reductase is involved in the development of benign prostatic
      hyperplasia. Triterpenoids isolated from ethanol extracts of Ganoderma lucidum
      (Fr.) Krast (Ganodermataceae) inhibited 5alpha-reductase activity. The presence
      of the C-3 carbonyl group and of the C-26-alpha,beta-unsaturated carbonyl group
      was characteristic of almost all inhibitors isolated from G. lucidum.

PMID- 16962783
TI  - Synthesis of carbon-11 labeled fluorinated 2-arylbenzothiazoles as novel
      potential PET cancer imaging agents.
AB  - Fluorinated 2-arylbenzothiazoles are new potential antitumor drugs, which show
      potent and selective inhibitory activity against breast, lung, and colon cancer
      cell lines. Carbon-11 labeled fluorinated 2-arylbenzothiazoles may serve as novel
      probes for positron emission tomography (PET) to image tyrosine kinase in
      cancers. The preparation of 4-fluorinated 2-arylbenzothiazoles 4-fluoro-2-(3
      benzloxy-4-methoxyphenyl)benzothiazole (6a) and 4-fluoro-2-(3,4
      dimethoxyphenyl)benzothiazole (6b) was achieved by a modification of Jacobson
      thioanilide radical cyclization chemistry. Hydrogenolytic cleavage of the benzyl
      ether group of compound 6a using H(2)/Pd-C provided the precursor 4-fluoro-2-(3
      hydroxy-4-methoxyphenyl)benzothiazole (7) for radiolabeling. Synthesis of
      radiolabeling precursors and the reference standards 5- and 6-fluorinated
      arylbenzothiazoles (11c-n) was achieved via the reaction of o-aminothiophenol
      disulfides with substituted benzaldehydes under reducing conditions. The target
      radiotracers carbon-11 labeled 4-, 5-, and 6-fluorinated arylbenzothiazoles (3
      [(11)C]6b, 4-[(11)C]11c, 3-[(11)C]11c, 5-[(11)C]11f, 4-[(11)C]11f, 4-[(11)C]11i,
      3-[(11)C]11i, 5-[(11)C]11l, and 4-[(11)C]11l) were prepared by O
      [(11)C]methylation of the phenolic hydroxyl precursors (7, 11d, 11e, 11g, 11h,
      11j, 11k, 11m, and 11n) with [(11)C]methyl triflate and isolated by solid-phase
      extraction (SPE) purification in 30-55% radiochemical yields.

PMID- 16962784
TI  - QSAR studies about cytotoxicity of benzophenazines with dual inhibition toward
      both topoisomerases I and II: 3D-MoRSE descriptors and statistical considerations
      about variable selection.
AB  - Deoxyribonucleic acid (DNA) topoisomerases are involved in diverse cellular
      processes, such as replication, transcription, recombination, and chromosome
      segregation. Searching new compounds that inhibit both topoisomerases I and II is
      very important due to the deficiency of the specific inhibitors to overcome
      multidrug resistance (MDR). A QSAR study was developed, employing the 3D-MoRSE
      descriptors and a set of 64 benzophenazines in order to model the inhibition of
      the topoisomerases I and II, expressed by the cytotoxicity of these compounds
      (IC(50)) versus drug-resistant human small cell lung carcinoma line cell H69/LX4.
      A comparison with other approaches such as the Topological, BCUT, Galvez
      topological charge indexes, 2D autocorrelations, Randic molecular profile,
      Geometrical, RDF, and WHIM descriptors was carried out. The mathematical models
      were obtained by means of the multiple regression analysis (MRA) and the
      variables were selected using the genetic algorithm. The model relative to the 3D
      MoRSE descriptors was considered as the best, taking into account its statistical
      parameters. It was able to describe more than 82.2% of the variance in the
      experimental activity once the outliers were extracted.

PMID- 16962785
TI  - Determination of manganese valency in La1-xSrxMnO3 using ELNES in the (S)TEM.
AB  - In this article several experimentally identified Mn valence-sensitive ELNES
      quantities for the La1-xSrxMnO3 compound class are presented, namely the energy
      separations between Mn-L3 and O-Ka, between O-Kb and O-Ka edges, the Mn-L2,3
      white line intensity ratio, and the Mn-L3 line width. Valence sensitivities of
      these quantities are evaluated, and possible additional influences on them are
      considered. At high signal-to-noise ratio the two energy separations display most
      sensitively changes of the Mn valency. An experiment-based estimation of the
      total uncertainties of the quantities indicates that at low signal-to-noise
      ratio, which is the case when studying interface effects at high spatial
      resolution, again both energy separations allow to resolve the smallest valency
      changes.

PMID- 16962786
TI  - Brain-derived neurotrophic factor does not influence age at neurologic onset of
      Huntington's disease.
AB  - In Huntington's disease (HD), genetic factors in addition to the HD CAG repeat
      mutation play a significant role in determining age at neurologic onset. Brain
      derived neurotrophic factor (BDNF), a survival factor for striatal neurons, has
      been implicated as a target of regulation by huntingtin and is an attractive
      candidate as a genetic modifier. We tested this hypothesis by genotyping a SNP
      known to alter BDNF function (rs6265, also termed Val66Met) and a SNP associated
      with Alzheimer disease (BDNF C270T), along with two BDNF intronic SNPs
      (rs7103411, rs11030104), in 228 cases with extreme young onset and 329 cases with
      extreme old onset of HD. No differences were seen between groups for allele
      frequencies or genotype frequencies for any SNP. Furthermore, no association to
      onset age was seen in GEE models controlling for HD repeat size or in haplotype
      analyses of these SNPs. These results indicate that BDNF does not influence
      significantly the mechanisms in HD pathogenesis that lead to neurologic onset.

PMID- 16962787
TI  - Influence of astaxanthin, zeaxanthin and lutein on DNA damage and repair in UVA
      irradiated cells.
AB  - In order to gain more knowledge about the antioxidant role of the predominant
      carotenoids (lutein and zeaxanthin) of the human retina, this study investigated
      their antioxidant activity and capacity. Astaxanthin was also studied, because
      its structure is very close to that of lutein and zeaxanthin. The antioxidant
      activity of these molecules was evaluated using chemiluminescence techniques,
      with lucigenin and luminol as chemiluminogenic probes for the superoxide radical
      and hydrogen peroxide, respectively. It was found that all three carotenoids have
      similar superoxide-scavenging activity. The effect on the reduction of H(2)O(2)
      luminol chemiluminescence was present in the following order,
      zeaxanthin>astaxanthinlutein. Possible antioxidant capacity of these three
      compounds was sought using a biological system consisting of SK.N.SH human
      neuroblastoma and rat trachea epithelial cells subjected to oxidative stress from
      exposure to UVA radiation. In particular, we determined whether these compounds
      were capable of minimizing DNA damage and influencing the kinetics of DNA repair.
      DNA damage was assessed using the Comet assay, a rapid and sensitive single-cell
      gel electrophoresis technique used to detect primary DNA damage in individual
      cells. Neuroblastoma cells appeared more resistant to oxidative irradiation
      insult. The presence of carotenoids reduced DNA damage when rat epithelial cells
      were exposed to UVA radiation for 2min. A different result was obtained in
      experiments performed on neuroblastoma cells; in this case, the presence of
      carotenoid during UVA exposition increased the damage. The addition of
      carotenoids to epithelial cells after 2min of UVA exposition did not seem to
      improve the kinetics of DNA repair; on the contrary, zeaxanthin (after 60'
      incubation) and lutein (after 180' incubation) showed a genotoxic effect. The
      addition of carotenoids to neuroblastoma cells after 30' UVA exposition
      positively influences the kinetics of DNA repair in the first 15min of
      incubation. At longer exposition times, while the behaviour measured was not
      constant, a genotoxic effect was not observed. The data from this study provide
      additional information on the antioxidant and pro-oxidant activities of the
      predominant macular pigment carotenoids of the human retina.

PMID- 16962788
TI  - Effects of water deficit on photosystem II photochemistry and photoprotection
      during acclimation of lyreleaf sage (Salvia lyrata L.) plants to high light.
AB  - Acclimation of photosynthetic light reactions to high light requires adjustments
      in photosystem II (PSII) photochemistry and may be affected by environmental
      stresses, such as water deficit. In this study, we examined the effects of this
      stress on PSII photochemistry and photoprotection, with an emphasis on the role
      of carotenoids and tocopherols, during acclimation of lyreleaf sage (Salvia
      lyrata L.) plants to high light. Violaxanthin was rapidly converted to zeaxanthin
      under high light, the de-epoxidation state of the xanthophyll cycle reaching
      maximum levels of 0.97 after 10 days of high light exposure. Under a higher
      photoprotective demand caused by water deficit, plants showed significant
      decreases in beta-carotene and enhanced oxidation of alpha-tocopherol to alpha
      tocopherol quinone, which was followed by decreases in the F(v)/F(m) ratio. The
      levels of beta-carotene decreased more in water-stressed than irrigated plants
      during acclimation to high light, being particularly degraded (up to 73%) after
      14 days of water deficit. Tocopherol levels increased significantly during
      acclimation to high light, particularly under water deficit, which caused 6.6-
      and 10-fold increases in alpha-tocopherol and alpha-tocopherol quinone,
      respectively. We conclude that when xanthophyll cycle-dependent excess energy
      dissipation could not afford further protection during high light acclimation and
      the photoprotective demand increased in lyreleaf sage plants by water deficit,
      enhanced oxidation of alpha-tocopherol and beta-carotene occurred. As stress
      persisted, enhanced formation of reactive oxygen species might ultimately damage
      the PSII, as indicated by the reductions in the F(v)/F(m) ratio.

PMID- 16962789
TI  - Amyloid beta peptide adversely affects spine number and motility in hippocampal
      neurons.
AB  - Elevated levels of amyloid-beta peptide (Abeta) are found in Down's syndrome
      patients and alter synaptic function during the early stages of Alzheimer's
      disease. Dendritic spines, sites of most excitatory synaptic contacts, are
      considered to be an important locus for encoding synaptic plasticity. We used
      time-lapse two-photon imaging of hippocampal pyramidal neurons in organotypic
      slices to study the effects of Abeta on the development of dendritic spines. We
      report that exposure of hippocampal neurons to sub-lethal levels of Abeta
      decreased spine density, increased spine length and subdued spine motility. The
      effect of Abeta on spine density was reversible. Moreover, Abeta's effect on
      dendritic spine density was blocked by rolipram, a phosphodiesterase type IV
      inhibitor, suggesting the involvement of a cAMP dependent pathway. These findings
      raise the possibility that Abeta-induced spine alterations could underlie the
      cognitive defects in Alzheimer's disease and Down syndrome.

PMID- 16962790
TI  - Cerebellar 'transcriptome' reveals cell-type and stage-specific expression during
      postnatal development and tumorigenesis.
AB  - Disorders of cerebellar development can result in neurological disease and
      cancer. The identity of transcription factors that may uniquely mark and/or
      regulate development of single cerebellar cell types, however, is poorly
      understood. We used a library of approximately 1100 probes for expression of
      transcription factor (TF)-encoding genes (>70% of the mammalian 'transcriptome')
      to identify 227 genes with expression in developing neuronal and glial
      populations and 24 TFs that show cell-type- and stage-specific expression in
      granule cells, Purkinje cells and interneurons during postnatal cerebellar
      development. The utility of this panel is exemplified by analysis of
      medulloblastoma that shows upregulation of markers specific for early granule
      cell lineage, but not for other neuronal cell types, indicative of a unipotent
      precursor as well as a block in granule cell differentiation within the tumor. We
      propose that this atlas of the cerebellar transcriptome and the panel of 24
      validated markers will be generally useful in analyses of mutations affecting
      postnatal cerebellar development and neoplasia.

PMID- 16962791
TI  - In vitro reconstitution and preparative purification of complexes between the
      chemokine receptor CXCR4 and its ligands SDF-1alpha, gp120-CD4 and AMD3100.
AB  - CXCR4 belongs to the family of G protein-coupled receptors and mediates the
      various developmental and regulatory effects of the chemokine SDF-1alpha. In
      addition, CXCR4 acts as a co-receptor along with CD4 for the HIV-1 viral
      glycoprotein gp120. Recently, there has also been a small molecule described that
      antagonizes both SDF-1 and gp120 binding to CXCR4. The structural and mechanistic
      basis for this dual recognition ability of CXCR4 is unknown largely due to the
      technical challenges of biochemically producing the components of the various
      complexes. We expressed the human CXCR4 receptor using a modified baculovirus
      expression vector that facilitates a single step antibody affinity purification
      of CXCR4 to >80% purity from Hi5 cells. The recombinant receptor undergoes N
      linked glycosylation, tyrosine sulfation and is recognized by the 12G5
      conformation specific antibody against human CXCR4. We are able to purify CXCR4
      alone as well as complexed with its endogenous ligand SDF-1, its viral ligand
      gp120, and a small molecule antagonist AMD3100 by ion-exchange chromatography. We
      anticipate that the expression and purification scheme described in this paper
      will facilitate structure-function studies aimed at elucidating the molecular
      basis for CXCR4 recognition of its endogenous chemokine and viral ligands.

PMID- 16962792
TI  - Microstructure and crystallographic-texture of giant barnacle (Austromegabalanus
      psittacus) shell.
AB  - Barnacle shell is a very complex and strong composite bioceramic composed of
      different structural units which consist of calcite 15 microcrystals of very
      uniform size. In the study reported herein, the microstructural organization of
      these units has been examinated in detail with optical and scanning electron
      microscopy, and X-ray diffraction techniques. These analyses showed that the
      external part of the shell has a massive microstructure consisting of randomly
      oriented crystals. Toward the interior, the shell became organized in mineral
      layers separated by thin organic sheets. Each of these mineral layers has a
      massive microstructure constituted by highly oriented calcite microcrystals with
      their c-axes aligned [(001) fibre texture] perpendicular to the organic sheets
      and the shell surface. Interestingly, in another structural unit, the shell
      shield, the orientation of the c-axis calcite crystals shifts from being
      perpendicular to being parallel to the shell surface across its thickness. This
      study provides evidence that the organic matrix is responsible for the
      organization of the shell mineral and exterts strong a strict control on the
      polymorphic type, size and orientation of shell-forming crystals.

PMID- 16962793
TI  - Stress and immune responses in abalone: limitations in current knowledge and
      investigative methods based on other models.
AB  - Increasing mariculture of abalone focuses attention on their immune and stress
      responses. For abalone, as well as many invertebrates, the function and
      relationship of these systems and how in vitro tests relate to them are not fully
      understood. This review focuses on research into the immune system and stress
      response conducted on abalone and on aspects that can be monitored in vitro. To
      fill the considerable knowledge gaps, we discuss work on other invertebrate taxa,
      concentrating on those closest to abalone, and making explicit the phylogenetic
      relations involved. The stress response appears to be very similar to that in
      vertebrates, but interpreting most immune responses remains problematic.
      Phylogeny must be considered: immune function tests derived from research into
      vertebrates or distantly related invertebrates should not be used in abalone
      until they have been validated in abalone by studies of susceptibility to
      pathogens. We suggest phagocytic activity of haemocytes and their efficiency in
      clearing bacteria are reliable parameters to measure, because they have been
      directly related to immune competency and are consistently depressed by stress.
      Carefully designed assays of antimicrobial activity may also be useful. Important
      aims of future research will be to investigate the relationship between growth,
      stress and robust immunity, and to develop tests that can be run on production
      animals, which accurately depict immune status.

PMID- 16962794
TI  - Distinct spatial patterns of brain activity associated with memory storage and
      search.
AB  - The time it takes for a human participant to decide whether a given stimulus is
      an element of a remembered set increases approximately linearly with the number
      of elements in the set. Here we tested for and detected a spatial pattern of
      brain activity whose magnitude of expression during this memory search process
      correlates with set size. We then tested the idea that memory search simply
      involves a re-activation of neurons involved in remembering the set by
      statistically comparing the patterns of brain activity corresponding to memory
      search and set size dependent working memory maintenance. These patterns were
      significantly different, suggesting that memory search and working memory
      maintenance are mediated by distinct neural mechanisms.

PMID- 16962795
TI  - Health-related quality of life and costs in patients with osteoarthritis on
      waiting list for total knee replacement.
AB  - OBJECTIVES: To determine: (1) health-related quality of life (HRQL) in patients
      with severe osteoarthritis (OA) on a waiting list (WL) for total knee replacement
      (TKR) and to compare it with general Spanish reference population values (RPVs);
      (2) the influence of sociodemographic and clinical variables on HRQL dimensions
      and (3) the use and cost of resources related to knee OA. METHODS: Cross
      sectional study. HRQL was measured by Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) and Medical Outcomes Study 36 Item Short Form Health
      Survey (SF-36) questionnaires. Sociodemographic and disease characteristics, body
      mass index, pharmacological treatment and the cost and use of economic resources
      related to knee OA during the 6-months previous to baseline were recorded.
      Relationships were analyzed using linear regression models. RESULTS: One hundred
      consecutive outpatients (71 female, mean age 71+/-6.89 years, mean disease
      duration 11.84+/-10.52 years) were included. Patients showed worse HRQL measured
      by SF-36 than the reference population, mainly in physical function, physical
      role and bodily pain dimensions (P<0.05). A low number of visits to physicians
      were recorded (mean 0.62+/-1.04). Total mean direct medical costs were 200.24
      euro (95%CI 167.08-233.40) and total mean direct non-medical costs were 1234.87
      euro (95%CI 812.74-1657.00). CONCLUSIONS: The HRQL of patients on a WL is worse
      than that of the reference population. The main costs of these patients were on
      non-medical resources, mainly due to functional limitations and loss of autonomy.
      The results suggest little compliance with knee OA management guidelines.

PMID- 16962796
TI  - Differentiation potential of an immortalized non-tumorigenic human liver
      epithelial cell line as liver progenitor cells.
AB  - We report the differentiation potential of an immortalized non-tumorigenic human
      liver epithelial cell line, THLE-5b. Under basic culture conditions THLE-5b
      showed undifferentiated phenotypes. When grown as cell aggregates, THLE-5b
      exhibited a hepatocyte-like ultrastructure, ammonia metabolic activity and
      several other indicators that suggest hepatocytic maturation, including up
      regulation or induction of liver-specific genes such as albumin and tryptophane
      2,3-dioxygenase, and down-regulation of biliary cell markers such as gamma
      glutamyl transpeptidase (GGT). Under these conditions, transcriptional factors
      such as HNF-1 and HNF-4alpha were also up-regulated or induced. In Matrigel
      culture, expression of GGT was up-regulated. THLE-5b expressed both albumin and
      alpha 1-antitrypsin, but lost expression of CK19 in severe combined
      immunodeficient mice. Thus, THLE-5b can be aligned with progenitor cells, which
      are committed to the hepatocytic or biliary epithelial cell lineage. These
      results imply that bipotent progenitor cell populations similar to THLE-5b cells
      may exist in adult human liver.

PMID- 16962797
TI  - Protein profiling and transcript expression levels of heat shock proteins in
      17beta-estradiol-treated human MCF-7 breast cancer cells.
AB  - Using proteomics, proteins regulated by 17beta-estradiol (E2) were identified in
      human MCF-7 breast cancer cells; 26 proteins including heat shock proteins (Hsps)
      were differentially regulated by E2 in cells cultured in serum-free condition.
      When the transcript levels of these proteins and another Hsps were measured by
      real-time PCR, the transcripts encoding 6 proteins (Hsp56, Hsp90alpha, Hsp110,
      protein disulfide isomerase related protein, XTP3-transactivated protein A and
      stathmin 1) were significantly up-regulated and that encoding aminoacylase 1 was
      down-regulated by E2 in cells cultured with or without serum. The protein
      profiling and transcript expression patterns of E2-regulated proteins including
      Hsps in MCF-7 cells suggested the involvement of these proteins in breast
      carcinogenesis. Proteins (or transcripts) whose expression pattern is altered by
      E2 might be potent targets for treating breast cancer patients.

PMID- 16962798
TI  - Dacron patch infection after carotid angioplasty. A report of 6 cases.
AB  - OBJECTIVE: We describe our experience with Dacron patch infections after carotid
      endarterectomy (CEA). REPORT: From 633 patients undergoing carotid endarterectomy
      with Dacron patching, six re-presented with prosthetic infections. In 3 of the 6
      cases a neck haematoma had necessitated surgical revision after the original
      carotid surgery. Five patients underwent interposition vein grafting and 1 vein
      patch angioplasty. Postoperatively, 2 patients developed a repeat infection
      including the 1 patient with patch angioplasty. All patients were free of
      infection and neurological symptoms after a maximum follow-up of 56.5 months.
      CONCLUSION: Following the development of haemorrhage or wound complications
      careful clinical surveillance should be carried out after carotid reconstruction.

PMID- 16962799
TI  - The superficial cervical plexus block for postoperative pain therapy in carotid
      artery surgery. A prospective randomised controlled trial.
AB  - OBJECTIVES: Rapid and reliable neurological evaluation soon after carotid artery
      surgery is feasible with modern methods of general anesthesia, but postoperative
      pain therapy remains a challenge. Use of opioids can mask neurological deficits.
      We investigated whether superficial cervical plexus block reduced postoperative
      opioid consumption after carotid endarterectomy. DESIGN: Prospective, randomised,
      double-blinded, placebo controlled trial. METHODS: 46 patients undergoing
      unilateral carotid endarterectomy under general anesthesia were randomized to
      either superficial cervical block with ropivacaine (n=23) or placebo (n=23). A
      patient controlled analgesia device (PCA) delivering morphine was provided for
      all patients. Subjective pain levels (visual analog scale, VAS) were recorded.
      The primary outcome was total morphine consumption on discharge from the recovery
      room. Secondary outcomes included arterial pCO2 (as an indicator of central
      nervous effects of morphine) and patient satisfaction. RESULTS: No adverse
      effects of the superficial cervical plexus block were reported. Four patients in
      the placebo group were excluded because of other drug use post-operatively. Per
      protocol analysis compared 23 patients in ropivacaine group and 19 patients in
      the placebo group. The ropivacaine group had a significant reduction in morphine
      consumption (3.8+/-2.0 versus 12.9+/-4.0, p<0.001), lower maximal pain scores
      (2.6+/-2.0 versus 5.8+/-1.6, p<0.001), and paCO2 levels (39.0+/-2.6 versus 41.9+/
      3.4, p=0.008) at discharge from the recovery room. Patient satisfaction (1=very
      good to 6=insufficient) was substantially higher in the ropivacaine group (1.7+/
      0.7 versus 3.1+/-1.2, p<00.01). CONCLUSION: The significant and clinically
      relevant lower morphine consumption and pain score, as well as the substantially
      higher patient satisfaction demonstrate that superficial cervical plexus block
      provides effective pain relief for patients undergoing carotid endarterectomy.

PMID- 16962800
TI  - A novel technique for imaging with inhomogeneous fields.
AB  - We introduce a simple, efficient, low-SAR method for magnetic resonance imaging
      in the presence of a static field with a permanent, and possibly large gradient.
      The technique, which is called slant-slice imaging is essentially a spin-echo
      imaging sequence except that the imaging slice is oriented such that the static
      field gradient can be used in conjunction with applied gradients during readout.
      Data are collected for 2D slices. Unlike single point imaging techniques, entire
      lines of k-space are acquired with each readout. The slant-slice pulse sequence
      is used to obtain high quality images, using a clinical scanner to simulate a
      static field with a large permanent gradient. The effects of the inhomogeneity
      are quantified by two parameters nu and q, which are useful for assessing the
      utility of a magnet design for 3D-MR imaging.

PMID- 16962801
TI  - Observation of anomalous diffusion in excised tissue by characterizing the
      diffusion-time dependence of the MR signal.
AB  - This report introduces a novel method to characterize the diffusion-time
      dependence of the diffusion-weighted magnetic resonance (MR) signal in biological
      tissues. The approach utilizes the theory of diffusion in disordered media where
      two parameters, the random walk dimension and the spectral dimension, describe
      the evolution of the average propagators obtained from q-space MR experiments.
      These parameters were estimated, using several schemes, on diffusion MR
      spectroscopy data obtained from human red blood cell ghosts and nervous tissue
      autopsy samples. The experiments demonstrated that water diffusion in human
      tissue is anomalous, where the mean-square displacements vary slower than
      linearly with diffusion time. These observations are consistent with a fractal
      microstructure for human tissues. Differences observed between healthy human
      nervous tissue and glioblastoma samples suggest that the proposed methodology may
      provide a novel, clinically useful form of diffusion MR contrast.

PMID- 16962802
TI  - Colony specificity and chemotaxis in the compound ascidian Botryllus schlosseri.
AB  - We re-investigated the behavior of hemocytes during the non-fusion (rejection)
      reaction between genetically incompatible colonies of the ascidian Botryllus
      schlosseri. In the course of the reaction, hemocytes - mainly morula cells -
      crowd inside the blind ends of marginal vascular vessels (known as ampullae) of
      the colonial leading edge (LE) facing the foreign colony which suggests the
      occurrence of chemotactic attraction of circulating hemocytes towards the
      ampullar lumen. Then, cells migrate, through the ampullar tips, into the
      partially fused tunics and contribute to the formation of the necrotic spots
      along the contact borders which characterize the reaction. Studies on
      histological sections clearly indicate that, although morula cell concentration
      is always higher in ampullae of the LE than in those of the lateral (L) part of
      the colony, their frequency significantly increases in LE ampullae of rejecting
      colonies with respect to LE ampullae of both fusing and isolated colonies. In
      addition, in vitro chemotaxis experiments demonstrated that blood plasma from
      incompatible colonies can stimulate morula cell migration through polycarbonate
      filters and this passage is inhibited by antibodies raised against mammalian pro
      inflammatory cytokines. The possible nature and role of molecules recognized by
      anti-cytokine antibodies in hemocyte migration are discussed.

PMID- 16962803
TI  - cDNA-derived amino acid sequences of myoglobins from nine species of whales and
      dolphins.
AB  - We determined the myoglobin (Mb) cDNA sequences of nine cetaceans, of which six
      are the first reports of Mb sequences: sei whale (Balaenoptera borealis), Bryde's
      whale (Balaenoptera edeni), pygmy sperm whale (Kogia breviceps), Stejneger's
      beaked whale (Mesoplodon stejnegeri), Longman's beaked whale (Indopacetus
      pacificus), and melon-headed whale (Peponocephala electra), and three confirm the
      previously determined chemical amino acid sequences: sperm whale (Physeter
      macrocephalus), common minke whale (Balaenoptera acutorostrata) and pantropical
      spotted dolphin (Stenella attenuata). We found two types of Mb in the skeletal
      muscle of pantropical spotted dolphin: Mb I with the same amino acid sequence as
      that deposited in the protein database, and Mb II, which differs at two amino
      acid residues compared with Mb I. Using an alignment of the amino acid or cDNA
      sequences of cetacean Mb, we constructed a phylogenetic tree by the NJ method.
      Clustering of cetacean Mb amino acid and cDNA sequences essentially follows the
      classical taxonomy of cetaceans, suggesting that Mb sequence data is valid for
      classification of cetaceans at least to the family level.

PMID- 16962804
TI  - Barbary sheep (Ammotragus lervia): the structure of the adult beta-globin gene
      and the functional properties of its hemoglobin.
AB  - The adult beta-globin gene of Ammotragus lervia (Barbary sheep or aoudad) has
      been sequenced completely, including 185 base pairs of 5' flanking region and 168
      base pairs 3' to the stop codon, and compared with that of other caprines such as
      goat (Capra hircus), wild Corsico-Sardinian (Ovis aries musimon) and Cypriot (O.
      a. ophion) mouflons, and domestic sheep (Ovis aries). The gene was identified as
      being located on a triplicated four-gene set cluster containing the HBBA locus (A
      haplotype) as is the case of goat, sheep of the Hb A type and Corsico-Sardinian
      mouflon. Phylogenetic analyses support the evidence that caprines share a common
      ancestor that probably carried the A-haplotype and that a more recent deletion of
      a gene set gave rise to the duplicated cluster containing the HBBB locus (B
      haplotype) found in sheep of the Hb B type and Cypriot mouflon, which evolved
      independently. Data also suggests that the Ammotragus beta-globin gene is older
      than genes of the examined caprines and indicates it followed an independent
      evolution after separating from species having the same HBBA locus. Similarly,
      phylogenetic analyses of beta-globin chain sequences suggest a different
      evolution for globins coded by the HBBA locus with respect to the HBBB.
      Ammotragus beta-globin chain shows all the amino acids responsible for the low
      oxygen affinity of ruminant Hbs. Investigations on the oxygen transport
      properties indicate that the intrinsic oxygen affinity of aoudad Hb is higher
      than the Hb B of the domestic sheep and, at the same time, more similar to that
      of other A type Hbs, whereas in the presence of the Cl(-) effector the oxygen
      affinity is approximately the same as that of the other species.

PMID- 16962805
TI  - Establishment of sister chromatid cohesion at the S. cerevisiae replication fork.
AB  - Two identical sister copies of eukaryotic chromosomes are synthesized during S
      phase. To facilitate their recognition as pairs for segregation in mitosis,
      sister chromatids are held together from their synthesis onward by the
      chromosomal cohesin complex. Replication fork progression is thought to be
      coupled to establishment of sister chromatid cohesion, facilitating
      identification of replication products, but evidence for this has remained
      circumstantial. Here we show that three proteins required for sister chromatid
      cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes
      with, replication forks. The ring-shaped cohesin complex is loaded onto
      chromosomes before S phase in an ATP hydrolysis-dependent reaction. Cohesion
      establishment during DNA replication follows without further cohesin recruitment
      and without need for cohesin to re-engage an ATP hydrolysis motif that is
      critical for its initial DNA binding. This provides evidence for cohesion
      establishment in the context of replication forks and imposes constraints on the
      mechanism involved.

PMID- 16962806
TI  - Multiple meningiomas: clinical, radiological, surgical, and pathological findings
      with outcome in four cats.
AB  - The present report describes the clinical signs, magnetic resonance imaging (MRI)
      findings, surgical procedure, pathological findings and follow-up in four cats
      with multiple meningiomas; three castrated male and one spayed female domestic
      shorthair indoor cats, ranging in age from 11 to 14 years. In three of four cats,
      clinical signs at presentation were suggestive of a focal lesion. Three cats had
      two meningiomas and one had four meningiomas. Most of the tumours were
      supratentorial, one arose from the tentorium and one was infratentorial. The
      duration of presenting signs before surgery ranged from 10 days to 11 months.
      Postoperative MRI revealed complete gross tumour removal in three cases. In one
      cat with two cranial fossa meningiomas, subtotal excision with a small basal
      remnant (2 x 2 mm) of the ventral part of one meningioma lying on the floor of
      the skull, was observed. Based on histopathological architecture, six tumours
      revealed features of a transitional subtype meningioma, and four of a
      meningotheliomatous meningioma. In each cat, the multiple meningiomas were all
      assigned to the same histopathological group. The preoperative presenting signs
      had resolved by the follow-up examinations 4 weeks after surgery in two cats.
      Long-term follow-up evaluation revealed that surgically-induced or exacerbated
      neurological deficits in two cats had completely or almost completely resolved
      within 8 weeks of surgery. All patients are still alive 12 to 21 months after
      surgery and no clinical signs of recurrence could be detected at that time.

PMID- 16962807
TI  - Genome-wide transcriptional response of Yersinia pestis to stressful conditions
      simulating phagolysosomal environments.
AB  - Yersinia pestis is a Gram-negative coccobacillus causing the dangerous disease,
      plague. Survival of Y. pestis within host macrophages is important in the initial
      stages of infection. In our present work, DNA microarray was used to determine
      the expression profiles of Y. pestis strain 201 in response to in vitro
      simulating conditions of Mg(2+) limitation, polymyxin treatment and oxidative
      stress that could be found in phagolysosomal environment. It was demonstrated
      that Y. pestis made appropriate adaptive/protective responses to survive the
      stressful environments. There are the induced expression of antiphagocytic
      factors and Mg(2+) transporters under Mg(2+) limitation condition, the
      stimulation of drug/analogue sensitivity and glycerol assimilation after
      polymyxin treatment, and the differential expression in genes encoding stress
      responsive proteins, components of cell envelope, iron assimilation and
      regulatory functions in response to both Mg(2+) limitation and polymyxin
      treatment. Under oxidative stress, Y. pestis uses several mechanisms, especially
      including the induced expression of detoxification enzymes and DNA repair
      proteins, to protect from or repair the oxidative cell damages. This microarray
      analysis would provide the candidates for identifying genes or pathways required
      for growth and proliferation of Y. pestis in macrophages.

PMID- 16962809
TI  - [Sequential assessment of individually cultured embryos in IVF].
AB  - OBJECTIVE: It is a challenge for IVF centers to propose a method to select the
      most viable embryo to transfer, thereby minimizing the risk of multiple births.
      In this study, a prospective investigation was made to determine if non-invasive
      developmental markers on day 1 combined to conventional evaluation on day 2 can
      predict in vitro blastocyst development. PATIENTS AND METHODS: A total of 4190
      individually cultured embryos from patients undergoing IVF/ICSI treatment at the
      Tours University Hospital Center from January 2002 to December 2004 were
      included. Individual embryos were cultured in sequential media in microdrops
      under mineral oil from j1 to j5/j6 allowing to record their sequential growth
      until the blastocyst stage. RESULTS: The results showed a significant positive
      relationship between pattern 0 zygote, early cleavage, 4 cells embryos with < 20%
      fragmentation on day 2 and the rate of blastocyst development on day 5 (P <
      0.05). In our hands, zygote pattern does not bring additional benefit to better
      select embryo. DISCUSSION AND CONCLUSION: Zygote and early cleavage assessments
      on day 1, morphological appearance on day 2 are some other parameters related
      individually to blastocyst development on days 5 and 6. These parameters can be
      used collectively to establish a predictive in vitro sequential embryo assessment
      model for routine use in IVF clinics.

PMID- 16962810
TI  - [DNA sperm methylation in assisted reproductive techniques].
AB  - In the last few years, many tests were developed to study the fertilizing
      properties of the spermatozoa. However none of them was useful to obtain a
      prognostic factor. Indeed, the integrity of the spermatic DNA is also necessary
      to a successful fertilization for obtaining a pregnancy. DNA integrity could be
      evaluated by the measurement of the level of DNA methylation. Indeed, in the
      mammals, the methylation of the ADN is involved in diverse processes amongst them
      the regulation of the genome expression during the embryonic development. The
      objective of this study is to evaluate the impact of the level of methylation of
      the spermatic DNA in the success of in vitro fertilization (IVF), in terms of
      rate of fertilization, quality of the embryos and rate of pregnancy. The
      immunostaining of the 5-methylecytosine, then the quantification by image
      analysis or with flow cytometry, allowed an objective evaluation of the level of
      total methylation of spermatic DNA. Our data show that the level of DNA
      methylation influences neither the fertilization rate nor the embryos quality. On
      the other hand, the rate of pregnancy is decreased if the total level of DNA
      methylation is lower than a threshold value. The level of spermatic DNA
      methylation represents a new parameter of spermatic maturation.

PMID- 16962811
TI  - [Spermatozoon mitochondrial DNA].
AB  - Mitochondria play a primary role in cellular energetic metabolism, homeostasis
      and death. In spermatozoa, in particular, mitochondria produce the ATP necessary
      for motility. Mitochondrial functions depend, at least partially, on
      mitochondrial DNA (mtDNA). The mitochondrial genome, the transmission of which is
      exclusively maternal contributes to cytoplasmic heredity. Qualitative and
      quantitative mtDNA abnormalities have been associated with male infertility. This
      review focuses on the role of mtDNA in human fertility.

PMID- 16962812
TI  - [Ovarian tissue vitrification: Cortex and whole ovary in sheep].
AB  - OBJECTIVE: The aim of this study was to evaluate a cryopreservation technique by
      vitrification of cortex or whole ovaries in sheep, using two cryoprotectant
      solutions: VS1 and VS4 and to study their physical properties to avoid ice
      crystallisation by vitrification of whole sheep ovaries permeated with a
      cryoprotectant solution. ANIMALS AND METHODS: From 6-month-old ewes, whole sheep
      ovaries with their vascular pedicles were collected at the slaughterhouse or at
      the veterinary school and prepared for cryoprotectant toxicity tests and freezing
      procedure. Follicle viability was measured by trypan blue test and histological
      examination of ovary. The hemi-ovarian cortex was stored in liquid nitrogen. Four
      to six weeks after the first laparotomy, the controlateral ovary was removed and
      the vitrified-warmed hemi-ovary was sutured. Thermal properties of a
      cryoprotectant solution called VS4 (critical cooling rates [Vccr], vitreous
      transition temperature [Tg], end of melting temperature [Tm]) were measured by
      differential scanning calorimetry. RESULTS: No significant difference in follicle
      viability or normal follicle rates was observed between ovarian cortex exposed or
      non-exposed to cryoprotectant solutions. Nor was any significant difference
      observed before and after vitrification. Three pregnancies occurred, from which
      four lambs were born after autografts of vitrified ovarian cortex. With whole
      ovary, the decrease in the number of normal follicles was lower when frozen
      thawed ovaries were treated with VS4 (P = 0.04). There were less nuclear
      anomalies (P = 0.02). The Vccr of VS4 has been estimated to be 14.3+/-1.1 degrees
      C/min and Tg was -125.0+/-0.2 degrees C. Because the penetration of
      cryoprotectants was very low, Vccr was very high and the cooling speed did not
      allow cortex to vitrify. DISCUSSION AND CONCLUSIONS: Cryopreservation of cortex
      or whole ovary by vitrification seems a promising technique in reproductive
      medicine. The best histologic results were obtained with the VS4 cryoprotectant
      when whole ovary was vitrified.

PMID- 16962813
TI  - [Cryopreservation and transfer of pig in vivo embryos: State of the art].
AB  - The present review article describes the development of porcine cryopreservation
      and transfer of embryos and the sanitary regulations related to these
      technologies. Rapid progress has been made during the last decade in
      cryopreservation by using vitrification which involves a very rapid cooling rate.
      Currently, this technology is suitable for morulae and blastocysts and to date,
      more than 300 piglets are born after surgical transfers of vitrified embryos.
      Moreover, farrowings are obtained after non-surgical transfers of fresh or
      vitrified embryos. However, further improvements are required to permit the
      dissemination of these technologies in the near future. According to the
      recommendations of the International Embryo Transfer Society (IETS) regarding
      international transportation, embryos must be washed and cryopreserved with an
      intact zona pellucida. Transmission by embryo transfer of virus or bacteria to
      swine has been studied and rather converging results are now published. The risk
      of disease transmission by the embryo transfer is reduced. The major advantage of
      these technologies is the possibility to transport and store genetic material
      whilst reducing the risks of pathogen transmission.

PMID- 16962814
TI  - [The comparison of the process of five different vitrification devices].
AB  - Over the last decade, several methods have been designed to improve the survival
      rate of vitrificated embryos. Although some teams have succeeded, the main
      remaining drawback of these methods is that they do not provide a leak proof
      environment for cryopreserved biological samples. To respond to that demand in
      respect with the European reglementation, the Cryo Bio System company (CBS)
      designed the HSV High Security Vitrification Kit (HSV). This system is composed
      of three distinct parts, a High Security thermal-autogenic sealed clear straw, a
      capillary with its extremity in form of a gutter, and an introducer that can be
      mounted on the manipulation rod before introduction into the straw. In this
      study, we confirmed that the CBS vitrification kit is a suitable method for
      vitrification in association with a small amount of cryoprotector enriched
      viscous media such as 25 microM Ficool 400, 750 mM Sucrose, 1% Bovine albumin,
      20% Dimethyl Sulfoxide and 20% Ethylene glycol in a Phosphate buffered saline
      solution. We also evaluated the speed of the temperature decrease during
      vitrification in comparison with four other commercially available non-aseptic
      methods and showed the protective role of the CBS system during transfer. These
      physical data have now been confirmed biologically by P. Vanderzwalmen who
      obtained easily reproductible good results with human embryo using our method.
      Today, the HSV represents the unique aseptic alternative device (EC and FDA
      approved) for embryos, oocytes, and biological samples vitrification.

PMID- 16962815
TI  - [Sociological aspects of late fatherhood].
AB  - Starting from a sociological research on late parenthood, the article shows
      quantitative and qualitative lessons on the subject--in particular concerning the
      fathers' perspective. Late parenthood has declined over the 20th Century, to
      increase again since 1980. The further exploitation of the survey EHF 99 shows
      the processes and the socio-demographic of late fatherhood, over three
      generations. This phenomenon is tightly related to the multiple descents and
      family recombinings. We also observe in these configurations major age
      differences between spouses and late relationship. The social bipolarity of this
      phenomenon appears clearly as far as late motherhood is concerned, but is less
      clear concerning fatherhood, since more blue collars and non qualified men are
      concerned. This difference is due to the important role played by migrants in
      this phenomenon. A qualitative survey conducted on the basis of biographic
      interviews has underlined the gendered logics of late family founding. These
      logics are linked to the discrepancies due to man/woman differences regarding
      their respective calendar of fertility and to their attitude towards work. The
      interviews which provide an analysis of the biographical processes of late
      parenthood are organised according to postponement or renewal logics, in the form
      of refoundation or repetition. They are linked to self-introspection and to the
      negotiations at work within a couple.

PMID- 16962817
TI  - Changing geographies of access to medical education in London.
AB  - This paper highlights the need for health geographers to consider the social and
      cultural geographies of who gets to train as a doctor. The paper presents a case
      study of a scheme intended to widen access to medical education for working class
      students from inner London. This work examines the role of local education
      markets and cultures of education in shaping the aspirations and achievements of
      potential future doctors. It employs ethnographic data to consider how 'non
      traditional' learners acclimatise to medical school. Our findings indicate that
      the students who succeed best are those who can see themselves as belonging
      within the education system, regardless of their social and cultural background.

PMID- 16962816
TI  - Bandaged penis.
AB  - This is a case of a male in his late 30s who died due to acute myocardial
      ischemia. His penis was bandaged. The penis was inflamed and had infected
      abrasions. The possible relevances of such an incidental finding and its
      contribution to sudden death is explored. The case report shows photographs of
      the bandage in situ and its components, inflammation of frenulum, injury to the
      shaft, and the generalized inflamed and mildly swollen penis. These changes were
      considered to be caused by bites. The micro-photographic findings in the case
      were of acute myocardial ischemia, pulmonary oedema, and fatty liver.

PMID- 16962818
TI  - Role of nucleotide excision repair deficiency in intestinal tumorigenesis in
      multiple intestinal neoplasia (Min) mice.
AB  - Mice deficient in the Xeroderma pigmentosum group A (Xpa) gene are defective in
      nucleotide excision repair (NER) and highly susceptible to skin carcinogenesis
      after dermal exposure to UV light or chemicals. Min (multiple intestinal
      neoplasia) mice, heterozygous for a germline nonsense mutation in the tumor
      suppressor gene adenomatous polyposis coli (Apc), develop intestinal tumors
      spontaneously and show additional intestinal tumors after exposure to the food
      mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). In this study, we
      investigated the impact of loss of XPA function on PhIP-induced intestinal
      tumorigenesis in F1 offspring of Min/+ (Apc(+/-)) mice crossed with Xpa gene
      deficient mice. Apc(+/-) mice lacking both alleles of Xpa had higher
      susceptibility towards toxicity of PhIP, higher levels of PhIP-DNA adducts in the
      middle and distal small intestines, as well as in liver, and a higher number of
      small intestinal tumors at 11 weeks, compared with Apc(+/-) mice with one or two
      intact Xpa alleles. Localization of tumors was not affected, being highest in
      middle and distal small intestines in all genotypes. At 11 weeks of age, the
      number of spontaneous intestinal tumors was not significantly increased by
      homozygous loss of Xpa, but untreated Apc(+/-)/Xpa(-/-) mice had significantly
      shorter life-spans than their XPA-proficient littermates. Heterozygous loss of
      Xpa did not affect any of the measured end points. In conclusion, the Xpa gene
      and the NER pathway are involved in repair of bulky PhIP-DNA adducts in the
      intestines and the liver, and most probably of DNA lesions leading to spontaneous
      intestinal tumors. These results confirm a role of the NER pathway also in
      protection against cancer in internal organs, additional to its well-known
      importance in protection against skin cancer. An effect of Apc(+/-) on adduct
      levels, additional to that of Xpa(-/-), indicates that the truncated APC protein
      may affect a repair pathway other than NER.

PMID- 16962819
TI  - 3LGM2-modeling to support management of health information systems.
AB  - OBJECTIVE: Both regional health information systems (rHIS) and hospital
      information systems (HIS) need systematic information management. Due to their
      complexity information management needs a thorough description or model of the
      managed information system. METHODS: The three layer graph-based meta-model
      (3LGM(2)) and the 3LGM(2) tool provide means for effectively describing and
      modeling HIS by hospital functions, application systems and physical data
      processing components. The 3LGM(2) tool has been used to model parts of the
      information system of the health care system of the German federal state Saxony
      and of the Leipzig University Medical Centre. RESULTS: Experiences showed, that
      3LGM(2) is suitable for supporting information management even in rHIS. We
      explain some benefits for information management in regional as well as local
      settings. CONCLUSIONS: Acceptance of the 3LGM(2) depends strictly on its
      integration in management structures on the institutional, regional, and even
      national or European level.

PMID- 16962820
TI  - Maribavir sensitivity of cytomegalovirus isolates resistant to ganciclovir,
      cidofovir or foscarnet.
AB  - BACKGROUND: The cytomegalovirus (CMV) UL97 inhibitor drug maribavir (MBV) is
      undergoing clinical antiviral trials. OBJECTIVES: To assess the MBV sensitivity
      of CMV strains and isolates containing mutations that confer resistance to
      current antiviral drugs ganciclovir, cidofovir or foscarnet. STUDY DESIGN:
      Resistant clinical isolates and laboratory strains containing UL97 and or UL54
      DNA polymerase mutations were tested for sensitivity to all four drugs by
      standard plaque reduction assay and a reporter-based yield reduction assay.
      Sensitive control strains were also tested. RESULTS: Eleven CMV strains or
      isolates resistant to GCV, four resistant to FOS and two resistant to CDV, were
      all sensitive to MBV. These viruses represent four UL97 mutations and three UL54
      DNA polymerase mutations. The laboratory derived UL97 L397R mutant was highly MBV
      resistant but remained sensitive to the other three drugs. CONCLUSIONS: No cross
      resistance has been detected between viruses resistant to MBV and those resistant
      to one or more of the current CMV antiviral drugs, consistent with differences in
      their mechanisms of action.

PMID- 16962821
TI  - Laboratory surveillance of dengue virus in Central Brazil, 1994-2003.
AB  - BACKGROUND: In Brazil, dengue endemic and epidemic patterns indicate an upward
      trend in incidence and hospitalization in the past decade. OBJECTIVE: To report
      dengue circulating serotypes from 1994 to 2003 and the role of distinct serotypes
      on dengue clinical outcomes in Central Brazil. METHODS: Virological surveillance
      for dengue cases was conducted in the city of Goiania ( approximately 1,200,000
      population) from 1994 to 2003. Samples were tested using dengue IgM antibody (MAC
      ELISA) and/or virus isolation. Circulating subtypes and genotypes were identified
      by reverse transcriptase PCR (RT-PCR) and by restricted site-specific PCR (RSS
      PCR) patterns in selected samples. RESULTS: Adults (87.4%) were the most affected
      group and dengue fever accounted for the majority of the cases. Laboratory
      surveillance identified mainly DEN 1 serotype from 1994 to 2002 shifting to a
      high circulation of DEN 3 in 2003. The ratio of dengue fever to dengue with
      complications/DHF remained constant following the introduction of DEN 3.
      Diagnosis of dengue was confirmed in approximately 50% of the suspected cases
      enhanced by RT-PCR. RSS-PCR patterns for DEN 1 and DEN 3 corresponded to the
      circulating subtypes in the country. CONCLUSIONS: The result of virological
      surveillance did not suggest a major role of infecting DEN 3 serotype in
      increasing disease severity during its first-year spread in Central Brazil.

PMID- 16962822
TI  - Calcium-independent phospholipase A2 and apoptosis.
AB  - Apoptosis or programmed cell death is associated with changes in
      glycerophospholipid metabolism. Cells undergoing apoptosis generally release free
      fatty acids including arachidonic acid, which parallels the reduction in cell
      viability. The involvement of cytosolic group IVA phospholipase A(2)alpha
      (cPLA(2)alpha) in apoptosis has been the subject of numerous studies but a clear
      picture of the role(s) played by this enzyme is yet to emerge. More recently, the
      importance of lipid products generated by the action of a second phospholipase
      A(2), the group VIA calcium-independent phospholipase A(2) (iPLA(2)-VIA) in
      apoptosis has begun to be unveiled. Current evidence suggests that iPLA(2)-VIA
      derived lysophosphatidylcholine may play a prominent role in mediating the
      chemoattractant and recognition/engulfment signals that accompany the process of
      apoptotic cell death, and gives possibility to the efficient clearance of dying
      cells by circulating phagocytes. Other lines of evidence suggest that
      perturbations in the control of free arachidonic acid levels within the cells, a
      process that may implicate iPLA(2)-VIA as well, may provide important cellular
      signals for the onset of apoptosis.

PMID- 16962823
TI  - Biochemical properties and pathophysiological roles of cytosolic phospholipase
      A2s.
AB  - Phospholipase A(2) (PLA(2)) (EC 3.1.1.4) catalyzes hydrolysis of the sn-2 ester
      bond of glycerophospholipids. The enzyme is essential for the production of two
      classes of lipid mediators, fatty acid metabolites and lysophospholipid-related
      lipids, as well as being involved in the remodeling of membrane phospholipids.
      Among many mammalian PLA(2)s, cytosolic PLA(2)alpha (cPLA(2)alpha) plays a
      critical role in various physiological and pathophysiological conditions through
      generating lipid mediators. Here, we summarize the in vivo significance of
      cPLA(2)alpha, revealed from the phenotypes of cPLA(2)alpha-null mice, and
      properties of newly discovered cPLA(2) family enzymes. We also briefly introduce
      a quantitative lipidomics strategy using liquid chromatography-mass spectrometry,
      a powerful tool for the comprehensive analysis of lipid mediators.

PMID- 16962824
TI  - NF-kappaB independent inhibition of lipopolysaccharide-induced cyclooxygenase by
      a conjugated linoleic acid cognate, conjugated nonadecadienoic acid.
AB  - 10t, 12c-CLA was shown to inhibit COX-2 expression through the NF-kappaB pathway.
      In the current study, conjugated nonadecadienoic acid (CNA) was shown to decrease
      inducible COX-2 protein and mRNA and PGE(2) release to the similar extent as 10t,
      12c-CLA in Raw264.7 macrophage. However, unlike 10t, 12c-CLA, inhibition of COX-2
      mRNA/protein by CNA was independent of the NF-kappaB pathway. The data indicate
      the regulation of COX-2 by select conjugated fatty acids and hence their anti
      inflammatory actions could operate through different signal transduction
      pathways.

PMID- 16962825
TI  - The interfacial binding surface of phospholipase A2s.
AB  - For membrane-associated enzymes, which access substrate from either a monolayer
      or bilayer of the aggregate substrate, the partitioning from the aqueous phase to
      this phospholipid interface is critical for catalysis. Despite a large and
      expanding body of knowledge regarding interfacial enzymes, the biophysical steps
      involved in interfacial recognition and adsorption remain relatively poorly
      understood. The surface of the enzyme that contacts the phospholipid surface is
      referred to as its interfacial binding surface, or more simply, its i-face. The
      interaction of a protein's i-face with the aggregate substrate may simply control
      access to substrate. However, it can be more complex, and this interaction often
      serves to allosterically activate the enzyme on this surface. First we briefly
      review what is currently known about i-face structure and function for a
      prototypical interfacial enzyme, the secreted Phospholipase A2 (PLA2). Then we
      develop, characterize, compare, and discuss models of the PLA2 i-face across a
      subset of five homologous PLA2 family members, groups IA, IB, IIA, V, and X. A
      homology model of human group-V is included in this comparison, suggesting that a
      similar approach could be used to explore interfacial function of any of the PLA2
      family members. Despite moderate sequence identity, structural homology and
      sequence similarity are well conserved. We find that the residues predicted to be
      interfacial, while conserved structurally, are not highly conserved in sequence.
      Implications for this divergence on interfacial selectivity are discussed.

PMID- 16962826
TI  - Descriptive characteristics of NCAA Division I women lacrosse players.
AB  - The purpose of this investigation was to describe anthropometric and physical
      performance characteristics of Division I college female lacrosse players. An
      additional aim of the study was to examine positional differences in this sample
      of athletes. Eighty-four university lacrosse players (age=19.8+/-1.1 years;
      height=168.3+/-5.9 cm; body mass=64.7+/-6.9 kg) volunteered to participate and
      were evaluated at the end of their off-season. Test items included standing
      height, body mass, linear sprint speed (9.14-36.58 m), agility (pro-agility and
      Illinois), countermovement jump height and the 20 Meter Shuttle Run Test (MSRT).
      Standing height was different between positions, pairwise comparisons indicating
      that attackers were taller than defenders (p=0.029). No other dependent variable
      differed between positions. Homogeneity between positions for women's lacrosse
      players indicates that the tests used do not have a high discriminatory value or
      could reflect the lack of development of positional specificity due to relatively
      minimal playing experience by participants. Although positional distinctions were
      not observed in this study, quartiles and ranges provide evidence that
      performance in female lacrosse players varies markedly.

PMID- 16962827
TI  - Combined decrease of defined B and T cell subsets in a group of common variable
      immunodeficiency patients.
AB  - Common variable immunodeficiency disease (CVID) is a primary immune disorder
      affecting B cells and characterized by hypogammaglobulinemia and recurrent
      infections. To elucidate the clinical and immunological heterogeneity of this
      condition, we have studied B and T cell subsets in 25 CVID patients. In eleven of
      them, we observed a remarkable relative expansion of a B cell subpopulation
      (CD19(hi)/CD21(lo) cells) characterized by the absence of CD23 and the reduced
      expression of the chemokine receptors CXCR5 and CCR7. Our analyses demonstrated
      in these patients that the expansion of CD19(hi)/CD21(lo) cells correlates with a
      selective decrease of circulating naive and CD21(hi) memory B lymphocytes. The
      same group of patients displayed a simultaneous severe reduction of naive CD4+ T
      cells associated with decreased levels of T cell receptor excision circles. These
      observations suggest that a combined defect in generation of B and T
      subpopulations may account for the abnormal immunophenotype characterizing this
      subgroup of CVID patients.

PMID- 16962828
TI  - 3D geometry of a normal tricuspid annulus during systole: a comparison study with
      the mitral annulus using real-time 3D echocardiography.
AB  - AIM: This study was done to explore the 3D geometry of the normal tricuspid
      annulus and compare it with the mitral annulus (MA), using real-time 3D
      echocardiography (RT3DE) and newly developed 3D computer software. METHODS:
      Thirteen left ventricular (LV) and 13 right ventricular (RV) volumetric images
      were obtained using RT3DE from normal subjects. LV and RV volumetric data were
      segmented into 16 rotational apical planes (angle increment=11.25 degrees )
      around the rotational axis from the apex through the center of two annuli, using
      newly developed 3D software (TomTec, Co., Munich, Germany). Two hinge points of
      the MA and the TA were traced in each plane during early and late systole. The MA
      and the TA were then automatically reconstructed with those 32 traced points. 3D
      surface (3DMAA, 3DTAA) and 2D projected areas (2DMAA, 2DTAA) of the annuli were
      calculated automatically as well, from those fitted data. For a comparison
      between the two annuli, the 3D and 2D area measurements of both annuli were
      corrected (c) according to the height of each patient (c2DMAA, c2DTAA, c3DMAA,
      and c3DTAA). Non-planarity of the annuli was estimated by their non-planar angles
      (MA: the angle between the anterior and posterior parts of the annulus; TA: the
      angle between the septal and free wall parts of the annulus). RESULTS: The TA
      revealed a less non-planar saddle shape than did the MA, which had a
      significantly wider non-planar angle (167.7+/-3.2 vs 145.5+/-6.1 degrees ,
      p<0.01) and a round or oval appearance on the projected view. The c2DTAA was
      significantly larger than the c2DMAA during early systole (p<0.01). However,
      there was no significant difference between the c3DTAA and c3DMAA during early
      and late systole (p>0.01). CONCLUSION: We assessed the 3D geometry of the MA and
      the TA by 3D reconstruction using RT3DE and newly developed computer software.
      The TA had a less non-planar shape compared with the MA, with either a round or
      oval appearance on the projected view.

PMID- 16962829
TI  - Multiallelic disruption of the rictor gene in mice reveals that mTOR complex 2 is
      essential for fetal growth and viability.
AB  - The rapamycin-insensitive mTOR complex 2 (mTORC2) has been suggested to play an
      important role in growth factor-dependent signaling. To explore this possibility
      further in a mammalian model system, we disrupted the expression of rictor, a
      specific component of mTORC2, in mice by using a multiallelic gene targeting
      strategy. Embryos that lack rictor develop normally until E9.5, and then exhibit
      growth arrest and die by E11.5. Although placental defects occur in null embryos,
      an epiblast-specific knockout of rictor only delayed lethality by a few days,
      thereby suggesting other important roles for this complex in the embryo proper.
      Analyses of rictor null embryos and fibroblasts indicate that mTORC2 is a primary
      kinase for Ser473 of Akt/PKB. Rictor null fibroblasts exhibit low proliferation
      rates, impaired Akt/PKB activity, and diminished metabolic activity. Taken
      together, these findings indicate that both rictor and mTORC2 are essential for
      the development of both embryonic and extraembryonic tissues.

PMID- 16962830
TI  - Visceral and orofacial somatic afferent fiber terminals converge onto the same
      neuron in paratrigeminal nucleus: An electron microscopic study in rats.
AB  - The paratrigeminal nucleus (Pa5) receives visceral sensory inputs through the
      vagus (X) and glossopharyngeal (IX) nerves and somatic sensory inputs through the
      trigeminal (V) nerve. In the present study, transganglionic transport of the WGA
      HRP and Wallerian degeneration was used to identify whether two kinds of primary
      afferent fiber terminals converge onto a single neuron in the Pa5 at the
      utrastructural level. It was found that HRP-labeled and degenerated terminals
      originating from the IX and/or X nerves and infraorbital nerve formed
      asymmetrical synapses with unlabeled dendrites in the Pa5. Furthermore,
      approximately 7% (43/630) HRP-labeled and 31% (43/137) degenerated terminals
      formed synaptic connections with the same dendritic profiles simultaneously in
      the dorsal division of the Pa5. These results may provide a neuroanatomical
      substrate for integration of viscerosomatic sensory inputs associated with
      visceral and cardiovascular reflexes in the Pa5.

PMID- 16962831
TI  - Studies of interactions among cobalt(III) polypyridyl complexes, 6-mercaptopurine
      and DNA.
AB  - The interactions between cobalt polypyridyl coordination compounds
      Co(L)(3)(3+)(L=1,10-phenanthroline(phen), and bipyridine(bpy)),6-mercaptopurine
      and calf thymus DNA have been investigated using electrochemical methods(cyclic
      voltammetry, differential pulse voltammetry), electronic absorption spectroscopy
      and viscosity measurements. Results indicate that there is an obvious interaction
      equilibrium between Co(L)(3)(3+), 6-mercaptopurine and DNA. The phenomena are
      investigated for the first time, and believed to be helpful to use the anticancer
      drugs more efficiently.

PMID- 16962832
TI  - Application of microfluidic chip with integrated optics for electrophoretic
      separations of proteins.
AB  - This paper describes the fabrication, the characterization and the applications
      of a capillary electrophoresis microchip. This hybrid device (glass/PDMS)
      features channels and optical waveguides integrated in one common substrate. It
      can be used for electrophoretic separation and fluorimetric detection of
      molecules. The microfluidic performance of the device is demonstrated by
      capillary zone and gel electrophoresis of proteins.

PMID- 16962833
TI  - Determination of plasma thiol bound to albumin using affinity chromatography and
      high-performance liquid chromatography with fluorescence detection: ratio of
      cysteinyl albumin as a possible biomarker of oxidative stress.
AB  - We examined the influence of oxidative stress on the relative amounts of various
      albumin-bound thiols in human plasma. To determine the ratio of thiols existing
      as mixed disulfides following oxidation, we developed a method combining fast
      purification of albumin using affinity columns and high-performance liquid
      chromatography (HPLC) with fluorescence detection for low molecular weight thiols
      which were labeled after reduction. When the effect of exposure of plasma to
      radical oxygen species on binding of thiols to albumin was determined by the
      present method, significant increases in the ratio of cysteine bound to albumin
      (Alb-Cys) to total cysteine were clearly demonstrated.

PMID- 16962834
TI  - The role of an absolutely conserved tryptophan residue in octamer formation and
      stability in mitochondrial creatine kinases.
AB  - In most organisms, mitochondrial creatine kinase (MtCK) is present as dimers and
      octamers with the latter predominating under physiological conditions. An
      absolutely conserved tryptophan residue (Trp-264 in chicken sarcomeric MtCK)
      appears to play a key role in octamer stability. Recently, it has been shown that
      the sponge Tethya aurantia, a member of the most ancient group of living multi
      cellular animals, expresses an obligate, dimeric MtCK that lacks this absolutely
      conserved tryptophan residue, instead possessing a tyrosine in this position. In
      the present study we confirm that the absolutely conserved tryptophan residue is
      lacking in other sponge MtCKs where it is instead substituted by histidine or
      asparagine. Site directed mutations of the Trp-264 in expression constructs of
      chicken sarcomeric MtCK and the octameric MtCK from the marine worm Chaetopterus
      destabilized the octameric quaternary structure producing only dimers. A Tyr-
      >Trp mutation in an expression construct of the Tethya MtCK construct failed to
      produce octamerization; Tyr-->His and Tyr-->Asn mutations also yielded dimers.
      These results, in conjunction with analysis of homology models of Chaetopterus
      and Tethya MtCKs, strongly support the view that while the absolutely conserved
      tryptophan residue is important in octamer stability, octamer formation involves
      a complex suite of interactions between a variety of residues.

PMID- 16962835
TI  - Mutant of Bungarus fasciatus acetylcholinesterase with low affinity and low
      hydrolase activity toward organophosphorus esters.
AB  - Enzymes hydrolysing highly toxic organophosphate esters (OPs) are promising
      alternatives to pharmacological countermeasures against OPs poisoning. Bungarus
      fasciatus acetylcholinesterase (BfAChE) was engineered to acquire organophosphate
      hydrolase (OPase) activity by reproducing the features of the human
      butyrylcholinesterase G117H mutant, the first mutant designed to hydrolyse OPs.
      The modification consisted of a triple mutation on the (122)GFYS(125) peptide
      segment, resulting in (122)HFQT(125). This substitution introduced a nucleophilic
      histidine above the oxyanion hole, and made space in that region. The mutant did
      not show inhibition by excess acetylthiocholine up to 80 mM. The k(cat)/K(m)
      ratio with acetylthiocholine was 4 orders of magnitude lower than that of wild
      type AChE. Interestingly, due to low affinity, the G122H/Y124Q/S125T mutant was
      resistant to sub-millimolar concentrations of OPs. Moreover, it had hydrolysing
      activity with paraoxon, echothiophate, and diisopropyl phosphofluoridate (DFP).
      DFP was characterised as a slow-binding substrate. This mutant is the first
      mutant of AChE capable of hydrolysing organophosphates. However, the overall
      OPase efficiency was greatly decreased compared to G117H butyrylcholinesterase.

PMID- 16962836
TI  - The development of cerebral connections during the first 20-45 weeks' gestation.
AB  - We have correlated data on neuroanatomical organization and magnetic resonance
      imaging of transient fetal zones shown to contain connectivity elements (growing
      axons, synapses, dendrites). In the fetal phase, afferent fibres 'wait' within
      the subplate zone which is the most prominent lamina on histological and magnetic
      resonance images and is a substrate of endogenous neuronal activity. In early
      preterm the thalamocortical afferents accumulate within the superficial subplate
      and grow into cortical plate developing synapses. In late preterm, the resolution
      of the subplate and growth of cortico-cortical fibres into the cortical plate
      occur simultaneously with gyration. Both preterm phases characterize the
      coexistence of endogenous and sensory-driven circuitries and occurrence of the
      transient electrical phenomena. In neonates, the long cortico-cortical pathways
      stop growth, and the main histogenetic events are an elaboration of intracortical
      circuitry and synaptogenesis. In conclusion, the growth of the axonal pathways
      preterm explains their vulnerability and plasticity. In neonates the
      vulnerability is related to the intracortical circuitry.

PMID- 16962837
TI  - Diffusion tensor imaging of brain development.
AB  - Understanding early human brain development is of great clinical importance, as
      many neurological and neurobehavioral disorders have their origin in early
      structural and functional cerebral organization and maturation. Diffusion tensor
      imaging (DTI), a recent magnetic resonance (MR) modality which assesses water
      diffusion in biological tissues at a microstructural level, has revealed a
      powerful technique to explore the structural basis of normal brain development.
      In fact, the tissue organization can be probed non-invasively, and the age
      related changes of diffusion parameters (mean diffusivity, anisotropy) reveal
      crucial maturational processes, such as white matter myelination. Nevertheless,
      the developing human brain presents several challenges for DTI applications
      compared with the adult brain. DTI may further be used to detect brain injury
      well before conventional MRI, as water diffusion changes are an early indicator
      of cellular injury. This is particularly critical in infants in the context of
      administration of neuroprotective therapies. Changes in diffusion characteristics
      further provide early evidence of both focal and diffuse white matter injury in
      association with periventricular leukomalacia in the preterm infant. Finally,
      with the development of 3D fiber tractography, the maturation of white matter
      connectivity can be followed throughout infant development into adulthood with
      the potential to study correlations between abnormalities on DTI and ultimate
      neurologic/cognitive outcome.

PMID- 16962838
TI  - Age-related effect on the concentration of collagen crosslinks in human osteonal
      and interstitial bone tissue.
AB  - Collagen crosslinks are important to the quality of bone and may be contributors
      to the age-related increase in bone fracture. This study was performed to
      investigate whether age and gender effects on collagen crosslinks are similar in
      osteonal and interstitial bone tissues. Forty human cadaveric femurs were
      collected and divided into two age groups: middle-aged (42-63 years of age) and
      elderly (69-90 years of age) with ten males and ten females in each group (n =
      10). Micro-cores of bone tissue from both secondary osteons and interstitial
      regions in the medial quadrant of the diaphysis were extracted using a custom
      modified, computer-controlled milling machine. The bone specimens were then
      analyzed using high performance liquid chromatography to determine the effects of
      age and gender on the concentration of mature, enzymatic crosslinks (hydroxylysyl
      pyridinoline-HP and lysyl-pyridinoline-LP) and a non-enzymatic crosslink
      (pentosidine-PE) at these two microstructural sites. The results indicate that
      age has a significant effect on the concentration of LP and PE, while gender has
      a significant effect on HP and LP. In addition, the concentration of the
      crosslinks in the secondary osteons is significantly different from that in the
      interstitial bone regions. These results suggest that the amount of non-enzymatic
      crosslinking may increase while that of mature enzymatic crosslinking may
      decrease with age. Such changes could potentially reduce the inherent quality of
      the bone tissue in the elderly skeleton.

PMID- 16962839
TI  - Detection of hearing impairment and handicap in Paget's disease of bone using a
      simple scoring system: a case control study.
AB  - Paget's disease of bone is known to be associated with hearing loss but there are
      limited data on the prevalence of hearing impairment and handicap in people with
      Paget's disease. Previous published population studies have used patient
      completed questionnaires or review of GP records, none have included audiometry.
      80 Paget's subjects were selected at random from a hospital database, 75 (94%)
      entered the study and were matched by age and gender with 76 controls. All
      participants completed a screening questionnaire for hearing handicap, the HHIE
      S; a questionnaire on perception of hearing-related handicap, noise exposure,
      hearing aids and GP consultations regarding hearing; and audiometry. The results
      show significant problems from hearing loss in people with Paget's disease of
      bone. Paget's patients were significantly more likely to perceive hearing
      handicap (P=0.0001), 41% Paget's patients rated themselves moderate-severe
      compared to none of the controls. Paget's patients were significantly more likely
      to report difficulties such as hearing normal speech, watching TV or hearing over
      background noise (all P=0.0001). They were more likely to consult their GP due to
      hearing problems (P=0.004) or tinnitus (P=0.0001), or use a hearing aid
      (P=0.0001). Audiometry confirmed higher rates of deafness in Paget's patients.
      41/75 Paget's patients compared to 19/76 controls had at least 40 decibels
      hearing loss (dBHL) (P=0.0001). The HHIE-S proved to be an effective screening
      tool. A score of greater than 8 increased the odds ratio of detecting moderate
      hearing impairment (>40 dBHL) in people with Paget's disease by 5.1. The
      specificity of HHIE-S >8 as a screening tool to select for audiometry appears
      good, 1/46 (2%) of Paget's patients would have proved to have normal hearing
      thresholds. The sensitivity is better with worse hearing loss, 7/16 Paget's
      patients with moderate loss (>40 dBHL) and 2/25 with severe-profound loss (>60
      dBHL) would have been missed. In conclusion, 55% unselected Paget's patients have
      at least moderate levels of hearing loss, compared to 25% of age and gender
      matched controls. Paget's patients and controls under-reported hearing problems,
      many of which can be ameliorated. Screening for hearing problems in Paget's
      disease of bone can be done using the HHIE-S.

PMID- 16962841
TI  - Cognitive impairment.
AB  - As populations continue to age, the prevalence of dementia is expected to
      increase. AD is by far the most common cause of dementia. The clinical course of
      dementia represents the challenges that this disease presents. There are no truly
      effective therapies for treating dementia, and the cost effectiveness of ChEIs
      has been challenged; however, there has been an explosion of information about
      AD. Evidence-based practice parameters for diagnosis and management of dementia
      have been developed. There has been an increased interest in the possible
      prodromal states of dementia, such as MCI. The concept of MCI has risen in
      prominence in recent years; it is speculated that initiation of therapies early
      in the course of disease may be needed for them to be effective. Considering the
      enormous burdens that AD places on individuals and society, disease-modifying
      treatments for AD are needed desperately. There are promising avenues for the
      development of potentially disease-modifying therapies for this devastating
      disease.

PMID- 16962842
TI  - Mood disorders in the elderly.
AB  - Mood disorders in the elderly are a growing source of morbidity and mortality.
      Unfortunately, mood disorders in later life frequently are not diagnosed and
      treated. Appropriate, prompt diagnosis and treatment of late-life mood disorders
      can significantly improve the quality of life of patients and families and may
      prove life saving. Current treatments can help most older adults with mood
      disorders. Future treatments are promising, particularly for those with treatment
      resistant depression.

PMID- 16962843
TI  - Falls and their prevention in elderly people: what does the evidence show?
AB  - A large proportion of falls and fall injuries in older people is due to multiple
      risk factors, many of which probably can be modified or eliminated with targeted
      fall prevention interventions. These interventions must be feasible, sustainable,
      and cost effective to be practical for widespread use. The most promising
      prevention strategies involve multidimensional fall risk assessment and exercise
      interventions. Incorporating these intervention strategies whenever feasible into
      a fall prevention program seems to be the most effective means for fall
      prevention in older adults.

PMID- 16962844
TI  - Urinary incontinence: selected current concepts.
AB  - UI is highly prevalent in older adults and associated with excess comorbidity and
      increased mortality. Intensive screening and comprehensive clinical examination
      of all elders enables prompt detection, accurate classification, and appropriate
      treatment. OAB is the most common cause of persistent incontinence in the older
      adult. As with other types of UI, behavior modification is first-line treatment
      of OAB. Although antimuscarinic agents have been shown to be highly effective in
      the treatment of OAB, limited data are available regarding the safety and
      tolerability of these agents in older adults. Patients who fail to respond to
      noninvasive treatment or those in whom surgery may be appropriate should be
      referred to the urologist for evaluation and further management.

PMID- 16962845
TI  - Frailty.
AB  - Frailty is a common condition in older people. It now can be objectively defined
      by the Fried criteria. When recognized, early intervention should begin with the
      institution of endurance, resistance, and balance exercises. In men with
      testosterone deficiency a trial of testosterone replacement should be considered.
      Vitamin D deficiency needs to be recognized and treated. Appropriate treatment of
      underlying diseases, such as anemia, diabetes mellitus, and congestive heart
      failure, are a key management principle. In people who have frailty aggressive
      health promotion and disease prevention techniques can lead to an inhibition of
      the downward spiral to disability.

PMID- 16962846
TI  - Heart disease and aging.
AB  - CAD is the most common cause of death in older persons and was present in 43% of
      1,160 men and in 41% of 2,464 women, mean age 81 years. Hypertension was present
      in 60% of these older women and in 57% of these older men. The prevalence of
      valvular aortic stenosis, aortic regurgitation, mitral regurgitation, and MAC
      increases with age in older men and in older women. The prevalence and incidence
      of CHF increase with age. CHF is the most common cause of hospitalization in
      persons aged 65 years and older. The prevalence of normal LV ejection fraction
      associated with CHF increases with age and is higher in older women than in older
      men. The prevalence of chronic atrial fibrillation increases with age and was
      present in 16% of 1,160 older men and in 13% of 2,464 older women. Atrial
      fibrillation is an independent predictor of new coronary events and
      thromboembolic stroke in older persons. Older persons who have unexplained
      syncope should have 24-hour ambulatory electrocardiograms to determine whether
      pauses of longer than 3 seconds are present that require permanent pacemaker
      implantation.

PMID- 16962847
TI  - Heart failure in older adults.
AB  - Heart failure affects approximately 5 million Americans, half of whom are at
      least 75 years of age, and is the leading cause of hospital admission among older
      adults. Additionally, the prevalence of heart failure is increasing, largely
      owing to the aging of the population. Heart failure in older adults differs in
      many respects from heart failure that occurs during middle age, including an
      increased proportion of women, increasing prevalence of heart failure with
      preserved left ventricular systolic function, and a marked increase in the number
      of coexisting medical conditions. In light of these factors, this article reviews
      the epidemiology, pathophysiology, clinical features, and treatment of heart
      failure in older adults.

PMID- 16962848
TI  - Nutritional disorders in the elderly.
AB  - Undernutrition is common in older people and has serious adverse effects. Weight
      loss and low body weight are key markers. Correctable causes, such as depression,
      are common and should be sought. Structured efforts to encourage food intake,
      together with nutritional supplements, often are of benefit. It is hoped that a
      better understanding of the underlying mechanisms will lead to targeted
      treatments. Overweight and obesity also are common in older people, and are
      associated with morbidity and impaired function. It is probably appropriate to
      recommend weight loss to obese older people who have associated comorbidities,
      particularly reduced mobility, but seldom, if ever, for increased weight alone.

PMID- 16962849
TI  - Diabetes in the elderly.
AB  - We are approaching an epidemic of diabetes in the elderly. This epidemic and its
      associated complications will have a significant impact on quality of life in
      this age group. Recent studies suggest that diabetes can be prevented in a large
      number of patients with appropriate interventions. It seems that diabetes in this
      age group is metabolically distinct. As a result, the approach to therapy in the
      elderly differs from that in younger patients. Unfortunately, we still have huge
      gaps in our understanding of the pathogenesis and treatment of diabetes in the
      aged, and further studies are needed urgently.

PMID- 16962850
TI  - Assessment and management of chronic pressure ulcers in the elderly.
AB  - Pressure ulcers remain a complex and costly problem to the health care system. As
      the population ages, a greater number of individuals will be at high risk for
      developing pressure ulcers. An understanding of the physiologic changes that
      occur with aging skin is important in preventing and treating chronic wounds.
      Risk factor assessment and modification, when possible, can help to reduce the
      development of pressure ulcerations. Although the goal continues to be
      prevention, once a pressure ulcer does occur, a systematic and comprehensive
      approach to assessment and treatment is necessary to reduce healing times.

PMID- 16962851
TI  - Elders with epilepsy.
AB  - Why is it important to learn about epilepsy in the elderly? The answers are many.
      As this article has highlighted, compared with younger individuals epilepsy is
      more common and the causes are more structural and symptomatic than in younger
      patients (particularly stroke). The clinical presentation is different in the
      elderly. The diagnosis is more difficult and often delayed. The most common
      seizures are simple partial and complex partial seizures, which are more often
      extratemporal in location. Confusion and memory problems are common presenting
      symptoms and postictal deficits often are prolonged. The prognosis for epilepsy
      in the elderly generally is favorable for seizure control, but if untreated,
      depression and quality of life suffer and seizures frequently recur. Seizures
      respond well at lower serum concentrations of antiepileptic drugs but these
      patients are also more sensitive (less tolerant) to side effects at lower doses
      than younger adults.

PMID- 16962852
TI  - The older cancer patient.
AB  - Providing effective and tolerable cancer treatment for the growing number of
      older adult patients who have cancer will require an understanding of the role of
      aging, comorbidity, functional status, and frailty on treatment outcomes. The
      incorporation of CGA into the care of older patients who have cancer will ensure
      that the heterogeneity of this population is considered in the development of
      treatment plans. It also may improve outcomes by identifying and optimally
      treating comorbid conditions and functional impairments. Optimal treatment of the
      older adult patient who has cancer starts with careful delineation of goals
      through conversation. The treatment plan should be comprehensive and address
      cancer-specific treatment, symptom-specific treatment, supportive treatment
      modalities, and end-of-life care.

PMID- 16962853
TI  - Palliative care and pain management.
AB  - Palliative care aims to improve quality of life and relieve suffering for
      patients with advanced illness and those close to them by specifically addressing
      communication, symptom management, coordination of care, psychosocial and
      spiritual realms, grief and bereavement support, and legal and ethical concerns.
      It has an interdisciplinary focus and may co-exist with curative and life
      prolonging treatment. Palliative care is a key component of appropriate, routine
      medical care, especially for clinicians caring for older adults. In revisiting
      Mrs. B, the many needs of a typical elderly patient are apparent, as are the gaps
      in the current level of care. A discussion of prognosis and goals of care is a
      potential starting point. This includes obtaining input from an oncologist with
      regard to treatment options for Mrs. B's metastatic breast cancer and her
      pathologic hip fracture. Soliciting her treatment goals in the context of her
      chronic obstructive pulmonary disease and significant recent decline is the next
      challenge. Pain, dyspnea, constipation, anorexia, and anxiety could then be
      addressed with pointed assessment and symptom-specific management. Code status
      discussion, communication with her support network, and care coordination for her
      increased care needs would follow. Hospice should be introduced as a potential
      option. Advance care planning might also be initiated. Psychological and
      spiritual support needs could also be explored in time. Clearly, there is much to
      be done for Mrs. B and her loved ones in clarifying and coordinating whatever
      path comes to be. Older patients and their families face prolonged courses of
      chronic disease and gradual decline. Physicians caring for these patients need to
      be expert in the domains of palliative care so these patients and their families
      can receive the best quality of care while they are still living full lives and
      later as they approach the end of life.

PMID- 16962854
TI  - Andropause: a quality-of-life issue in older males.
AB  - Testosterone deficiency occurs commonly in men as they grow older. This
      deficiency often is associated with a decline in sexual activity and a loss of
      muscle mass. Testosterone replacement can reverse many of these effects. At
      present, no ideal form of testosterone replacement is available. Like the
      phosphodiesterase-5 inhibitors, testosterone replacement in older men is a
      quality of life issue.

PMID- 16962855
TI  - Aging and sexuality.
AB  - Sexuality, although only one aspect of one's being, plays an integral role during
      the aging process. This role has physical and psychologic ramifications. A
      healthy sexual attitude combined with addressing physical health needs provides a
      greater potential for enjoying a more fulfilled lifestyle as one ages. With aging
      come significant potential medical problems and associated psychologic
      disturbances. These issues present a challenge to those in the medical profession
      who treat this age group. It is important to those physicians accepting this
      responsibility to become extremely familiar with all the nuances affecting those
      in the golden years of their lives. This enormous responsibility requires
      knowledge, caring, compassion, understanding, and sensitivity. With luck, we will
      all reach those golden years and receive the freedom to experience and express
      sexuality that is most certainly deserved.

PMID- 16962857
TI  - Effective implementation of the Human Tissue Act.

PMID- 16962858
TI  - Recognising the rights of individuals with disabilities.

PMID- 16962859
TI  - The Health Systems Action Network: a promising start.

PMID- 16962860
TI  - Does the metabolic syndrome help to select patients requiring high statin dose?

PMID- 16962861
TI  - Medical therapy for premature ejaculation.

PMID- 16962862
TI  - Prevention of mortality from hepatitis B and hepatitis C.

PMID- 16962863
TI  - Universal prenatal herpes screening is a bad idea in pregnancy.

PMID- 16962864
TI  - Dissent over harm reduction for tobacco.

PMID- 16962865
TI  - Serial interviews for patients with progressive diseases.

PMID- 16962866
TI  - Drug bulletins: independent information for global use.

PMID- 16962867
TI  - Naeema Al Gasseer: defending public health in Iraq.

PMID- 16962868
TI  - Incubation period of human prion disease.

PMID- 16962869
TI  - Incubation period of human prion disease.

PMID- 16962870
TI  - Incubation period of human prion disease.

PMID- 16962872
TI  - Incubation period of human prion disease.

PMID- 16962873
TI  - The Trivacan study.

PMID- 16962874
TI  - The Trivacan study.

PMID- 16962875
TI  - Infant mortality among Australian Aboriginals.

PMID- 16962878
TI  - Financial deficits in the health services of the UK and Hungary.

PMID- 16962879
TI  - Chikungunya re-emergence: possible mechanisms.

PMID- 16962880
TI  - Alcohol abuse in Poland.

PMID- 16962881
TI  - Reduction of low-density lipoprotein cholesterol in patients with coronary heart
      disease and metabolic syndrome: analysis of the Treating to New Targets study.
AB  - BACKGROUND: Despite the prognostic value of metabolic syndrome for predicting
      cardiovascular events, few trials have investigated the effects of statin therapy
      on cardiovascular morbidity and mortality in patients with the metabolic
      syndrome. Our post hoc analysis of the Treating to New Targets (TNT) study
      assessed whether intensive lowering of low-density lipoprotein cholesterol with
      high-dose atorvastatin therapy results in cardiovascular benefits for patients
      with both coronary heart disease and the metabolic syndrome. METHODS: The TNT
      study was a prospective, double blind, parallel-group trial done at 256 sites in
      14 countries between April, 1998, and August, 2004, with a median follow-up of
      4.9 years. 10,001 patients were enrolled aged 35-75 years with clinically evident
      coronary heart disease. Our analysis includes 5584 patients with metabolic
      syndrome based on the 2005 NCEP ATP III criteria. Patients were randomly assigned
      to receive either atorvastatin 10 mg per day (n=2820) or 80 mg per day (n=2764).
      The primary outcome measure was time to first major cardiovascular event, defined
      as death from coronary heart disease, non-fatal non-procedure-related myocardial
      infarction, resuscitated cardiac arrest, or fatal or non-fatal stroke. FINDINGS:
      In patients with coronary heart disease and metabolic syndrome, mean on-treatment
      low-density lipoprotein cholesterol concentrations at 3 months were 2.6 mmol/L
      (99.3 mg/dL) with atorvastatin 10 mg, and 1.9 mmol/L (72.6 mg/dL) with
      atorvastatin 80 mg. At a median follow-up of 4.9 years, major cardiovascular
      events occurred in 367 (13%) patients receiving atorvastatin 10 mg, compared with
      262 (9.5%) receiving atorvastatin 80 mg (hazard ratio 0.71; 95% CI 0.61-0.84;
      p<0.0001). Irrespective of treatment assignment, significantly more patients with
      metabolic syndrome (11.3%) had a major cardiovascular event at a median of 4.9
      years than those without metabolic syndrome (8.0%; hazard ratio 1.44; 95% CI 1.26
      1.64; p<0.0001). This increased risk was significantly reduced by intensive
      therapy with atorvastatin 80 mg beyond that achieved with atorvastatin 10 mg.
      INTERPRETATION: These data indicate that patients with coronary heart disease and
      metabolic syndrome derive incremental benefit from high-dose atorvastatin
      therapy, irrespective of the presence of diabetes.

PMID- 16962882
TI  - Efficacy and tolerability of dapoxetine in treatment of premature ejaculation: an
      integrated analysis of two double-blind, randomised controlled trials.
AB  - BACKGROUND: No drugs are approved for treatment of premature ejaculation. Our aim
      was to determine the efficacy and tolerability of on-demand dapoxetine in
      patients with severe premature ejaculation. METHODS: We determined the efficacy
      of dapoxetine in a prospectively predefined integrated analysis of two 12-week
      randomised, double-blind, placebo-controlled, phase III trials of identical
      design done independently, in parallel, at 121 sites in the USA. Men with
      moderate-to-severe premature ejaculation in stable, heterosexual relationships
      took placebo (n=870), 30 mg dapoxetine (874), or 60 mg dapoxetine (870) on-demand
      (as needed, 1-3 h before anticipated sexual activity). The primary endpoint was
      intravaginal ejaculatory latency time (IELT) measured by stopwatch. Safety and
      tolerability were assessed. All analyses were done on an intention-to-treat
      basis. The trials are registered at ClinicalTrials.gov, numbers NCT00211107 and
      NCT00211094. FINDINGS: 672, 676, and 610 patients completed in the placebo, 30 mg
      dapoxetine, and 60 mg dapoxetine groups, respectively. Dapoxetine significantly
      prolonged IELT (p<0.0001, all doses vs placebo). Mean IELT at baseline was 0.90
      (SD 0.47) minute, 0.92 (0.50) minute, and 0.91 (0.48) minute, and at study
      endpoint (week 12 or final visit) was 1.75 (2.21) minutes for placebo, 2.78
      (3.48) minutes for 30 mg dapoxetine, and 3.32 (3.68) minutes for 60 mg
      dapoxetine. Both dapoxetine doses were effective on the first dose. Common
      adverse events (30 mg and 60 mg dapoxetine, respectively) were nausea (8.7%,
      20.1%), diarrhoea (3.9%, 6.8%), headache (5.9%, 6.8%), and dizziness (3.0%,
      6.2%). INTERPRETATION: On-demand dapoxetine is an effective and generally well
      tolerated treatment for men with moderate-to-severe premature ejaculation.

PMID- 16962883
TI  - Causes of death after diagnosis of hepatitis B or hepatitis C infection: a large
      community-based linkage study.
AB  - BACKGROUND: Hepatitis B and hepatitis C virus infections are common causes of
      death related to liver disease. In this large study, we aimed to investigate all
      cause mortality of the viruses in a community-based setting. METHODS: In the
      study population, 39,109 people had hepatitis B, 75,834 had hepatitis C, and 2604
      had hepatitis B and hepatitis C co-infection, notified to the New South Wales
      state health department, Australia, between 1990 and 2002. Their data were
      probabilistically linked to the National Death Index. Standardised mortality
      ratios for all causes of death were calculated and adjusted for age, sex, and
      calendar year. RESULTS: The number of deaths identified by the linkage were 1233
      (3.2%) for hepatitis B, 4008 (5.3)% for hepatitis C, and 186 (7.1)% for hepatitis
      B and C co-infection. Raised risk of liver-related death (standardised mortality
      ratios 12.2, 95% CI 10.7-13.9; 16.8, 15.4-18.3, and 32.9, 23.1-46.7, for
      hepatitis B, hepatitis C, and hepatitis B and C co-infected patients,
      respectively) and drug-induced death (1.4, 1.0-2.0; 19.3, 18.1-20.5; and 24.7,
      18.2-33.5, respectively) were detected. In people with hepatitis C, raised risk
      of dying from drug-related causes was significantly greater than from liver
      related causes (p=0.012), with the greatest excess risk in women aged 15-24 years
      (56.9, 39.2-79.9). INTERPRETATION: All groups had increased risk of liver-related
      death compared with the standard population, with the greatest excess in people
      diagnosed with hepatitis B and hepatitis C co-infection. Our data highlight that
      young people with hepatitis C and with co-infection face a higher mortality risk
      from continued drug use than from their infection, whereas the main cause of
      hepatitis B death was liver related.

PMID- 16962884
TI  - A kidney non-transplantable.

PMID- 16962885
TI  - Novel strategies for stimulating erythropoiesis and potential new treatments for
      anaemia.
AB  - As with many other therapeutic areas in modern-day medicine, scientific advances
      in drug development (using such techniques as recombinant DNA technology, site
      directed mutagenesis, pegylation of molecules, peptide library screening, and
      gene transfer) have resulted in the development of potential new agents and
      strategies for stimulating erythropoiesis. These advances are of possible benefit
      in treating anaemia due to various causes, including chronic renal failure.
      Several new treatments will soon become clinically available, while others are at
      present at an early stage of development but are nevertheless of scientific
      interest. We review these new therapeutic strategies, and discuss at what stage
      some of the newer products are in relation to their clinical development
      programme.

PMID- 16962886
TI  - Bridging the divide: global lessons from evidence-based health policy in Mexico.
AB  - During the past 6 years, Mexico has undergone a large-scale transformation of its
      health system. This paper provides an overview of the main features of the
      Mexican reform experience. Because of its high degree of social inequality,
      Mexico is a microcosm of the range of problems that affect countries at all
      levels of development. Its health system had not kept up with the pressures of
      the double burden of disease, whereby malnutrition, common infections, and
      reproductive health problems coexist with non-communicable disease and injury.
      With half of its population uninsured, Mexico was facing an unacceptable paradox:
      whereas health is a key factor in the fight against poverty, a large number of
      families became impoverished by expenditures in health care and drugs. The reform
      was designed to correct this paradox by introducing a new scheme called Popular
      Health Insurance (Seguro Popular). This innovative initiative is gradually
      protecting the 50 million Mexicans, most of them poor, who had until now been
      excluded from formal social insurance. This paper reports encouraging results in
      the achievement of the ultimate objective of the reform: universal access to high
      quality services with social protection for all.

PMID- 16962887
TI  - Vulvar ulceration with an unexpected underlying cause.

PMID- 16962888
TI  - Signaling pathways mediating chemotaxis in the social amoeba, Dictyostelium
      discoideum.
AB  - Chemotaxis, or cell migration guided by chemical cues, is critical for a
      multitude of biological processes in a diverse array of organisms. Dictyostelium
      discoideum amoebae rely on chemotaxis to find food and to survive starvation
      conditions, and we have taken advantage of this system to study the molecular
      regulation of this vital cell behavior. Previous work has identified
      phosphoinositide signaling as one mechanism which may contribute to directional
      sensing and actin polymerization during chemotaxis; a mechanism which is
      conserved in mammalian neutrophils. In this review, we will discuss recent data
      on genes and pathways governing directional sensing and actin polymerization,
      with a particular emphasis on contributions from our laboratory.

PMID- 16962889
TI  - We're not laughing.

PMID- 16962891
TI  - Capnography & MCI.

PMID- 16962894
TI  - Mixed reviews.

PMID- 16962896
TI  - The 80/20 rule.

PMID- 16962897
TI  - More time-savers for ambulance-washers.

PMID- 16962898
TI  - Networking 101.

PMID- 16962899
TI  - Case of the month. The details prevail.

PMID- 16962901
TI  - Is knowledge power?

PMID- 16962902
TI  - Aftermath. Five years after 9/11, health issues surface among EMS responders.

PMID- 16962903
TI  - Lessons learned from 9/11.

PMID- 16962904
TI  - Crushed. How proper treatment of Crush Syndrome saved police Sgt. John McLoughlin
      after 22 hours under WTC rubble.

PMID- 16962905
TI  - Live from Loma Linda. Telemedicine project brings tertiary care center to the
      field.

PMID- 16962906
TI  - Breathable PPE. New fabric blocks virus transmission.

PMID- 16962907
TI  - No comfort in the comfort room.

PMID- 16962908
TI  - Patient's voice in health professional education.

PMID- 16962909
TI  - Intimate examination teaching with volunteers: implementation and assessment at
      the University of Antwerp.
AB  - OBJECTIVES: Teaching intimate physical examinations in medical schools generates
      practical, didactical and ethical problems. At the University of Antwerp, a
      unique program with intimate examination assistants (IEA) was implemented for
      fifth year's undergraduate students. They learn gynaecological and urological
      skills in healthy volunteers. Technical, communicative and attitude aspects are
      taken into account. METHODS: Description of the implementation of the project.
      Assessment of the project by questionnaires, written reflections and round table
      conferences. RESULTS: The results provide detailed information about the
      student's perceptions of each component of the program as well as the perceptions
      of the IEA's and the teachers. CONCLUSION: The multilevel evaluation of the
      program supports the surplus value of working with IEA's in medical education.
      The eye-catcher in this program is the integration of clinical skills with
      communicative skills and attention for students' attitude. PRACTICE IMPLICATIONS:
      Working with IEA's for intimate examinations represents a benefit in medical
      education by lowering the student's threshold to perform the intimate physical
      examination on both men and women during their fulltime clerkships.

PMID- 16962910
TI  - Print information to inform decisions about mammography screening participation
      in 16 countries with population-based programs.
AB  - OBJECTIVE: To profile and compare the content and presentation of written
      communications related to informed decision-making about mammography. METHODS:
      Materials from 16 screening programs organized at the national or regional level
      were analyzed according to five major information domains suggested by the
      international literature. RESULTS: A majority of countries provided information
      on the program (interval, cost and quality). There was considerable variability
      in comprehensiveness of elements in the domains, e.g., test characteristics
      (false positive/negative) and pros and cons of screening. The majority noted the
      likelihood of recall for further tests, few commented on the risks of additional
      tests or finding unimportant tumors. The audit also found variation in
      presentation (words and pictures). CONCLUSIONS: Presentation of comprehensive,
      but balanced information on screening benefits and risks is complex and daunting.
      Issues such as framing effects, coupled with debate about screening efficacy are
      challenging to the design of effective information tools. The objective of
      increasing screening prevalence at the population level must be balanced with
      objectively presenting complete and clear information. Additional research is
      needed on how information (and mode of presentation) impact screening decisions.
      PRACTICE IMPLICATIONS: Public health officials need to articulate their
      objectives and review written communication according to important decision
      making domains.

PMID- 16962913
TI  - Thrombophilia and women's health: An overview.
AB  - Thrombophilia, whether inherited or acquired, is one of the hot topics in women's
      health. Several factors, some of which are specific to the female patient,
      enhance thrombus formation in the presence of thrombophilia and include oral
      contraception, hormone replacement therapy, pregnancy, and puerperium. Thrombotic
      events are not only restricted to venous thromboembolism but also are believed to
      cause repeated embryonic loss, fetal loss, placental abruption, intrauterine
      growth restriction, and severe pre-eclampsia. It seems that some thrombophilias,
      and a combination of thrombophilic factors, carry a greater risk than others for
      a given adverse outcome. The addition of LMWH to the armamentarium was associated
      with conceptual change in the practice of anticoagulation. Care should be
      exercised in the interpretation of various risks and the potential of
      anticoagulation as a remedy to reduce that risk.

PMID- 16962914
TI  - Inherited thrombophilias.
AB  - Many inherited thrombophilias have been detected and the pathophysiologic insight
      has increased tremendously during the last decades. Despite, however, the
      overwhelming observational evidence on the association between inherited
      thrombophilia and several women's health issues, including VTE, thus far the
      implications for clinical practice are uncertain. Although there is firm
      epidemiologic evidence that is helpful in counseling women who have inherited
      thrombophilia to prevent a first or recurrent VTE, the uncertainty is
      particularly present for women who have other pregnancy complications, such as
      recurrent pregnancy loss and pre-eclampsia. For this group, well-designed placebo
      controlled trials to assess the harm-benefit ratio are urgently needed.

PMID- 16962915
TI  - Acquired thrombophilia during pregnancy.
AB  - Acquired thrombophilic states are common causes of thrombosis and other forms of
      pregnancy-associated complications. A growing body of evidence is available to
      guide the use of anticoagulants in patients who have antiphospholipid antibodies;
      unfortunately, the results of these studies are conflicting, and solid, evidence
      based treatment recommendations cannot be made. Other forms of acquired
      thrombophilia are uncommon or of unknown clinical significance. Treatments aimed
      at mitigating the impacts of these states lack clear evidence to support their
      use.

PMID- 16962916
TI  - Screening for thrombophilia.
AB  - Thrombophilia screening may be useful in patients at high risk of VTE because it
      may improve clinical outcome. Family screening allows primary prophylaxis for
      high-risk situations and counseling of women considering hormonal therapy and
      pregnancy. Until we find useful and inexpensive screening tools, it is not
      recommended to test every patient or her/his relatives. Each index case should be
      carefully evaluated by an expert physician who should tailor the laboratory
      testing and treatment modalities.

PMID- 16962917
TI  - Monitoring the effects and managing the side effects of anticoagulation during
      pregnancy.
AB  - LMWHs are the major anticoagulant/antithrombotic treatment given to pregnant
      women to prevent and treat venous thromboembolism despite the absence of specific
      clinical trials. An emerging indication, the prevention of adverse pregnancy
      outcomes, is under investigation. During pregnancy, LMWHs seem to be safe and
      efficient. Some uncertainties remain about the management of rare potential side
      effects, particularly in the event of heparin intolerance and with cross
      reactivity to danaparoid sodium.

PMID- 16962918
TI  - Thrombophilia and the risk for venous thromboembolism during pregnancy, delivery,
      and puerperium.
AB  - The main inherited thrombophilias (antithrombin deficiency, protein C and S
      deficiency, FVL, the prothrombin gene variant, and MTHFR C677T homozygotes) have
      a combined prevalence in Western European populations of 15% to 20%. One or more
      of these inherited thrombophilias is usually found in approximately 50% of women
      who have a personal history of VTE. Obstetricians must therefore be aware of the
      interaction between thrombophilias and the procoagulant state of pregnancy and
      should have an understanding of additional risk factors that may act
      synergistically with thrombophilias to induce VTE. Such knowledge combined with
      the appropriate use of thromboprophylaxis and treatment in women who have
      objectively confirmed VTE continue to improve maternal and perinatal outcomes.

PMID- 16962919
TI  - Thrombophilia and recurrent pregnancy loss.
AB  - Many unanswered questions regarding thrombophilia and recurrent pregnancy loss
      exist. For example, does a true association exist? Are thrombotic mechanisms
      relevant? Is a second messenger necessary to cause the manifestation of
      thrombosis? At present it seems that thrombophilia are associated with and may
      even cause some cases of pregnancy loss. The role of treatment remains to be
      determined. Although the aim of physicians working in this field is entirely
      laudable, to allow childless couples to have children, it is necessary to have
      good evidence of effect before treatment is given to all patients. A serious
      ethical dilemma remains, however, namely should treatment that may be effective
      be denied to patients who have prior pregnancy losses? Denial of treatment is
      extremely distressing for the patient and the physician. The author's own
      practice is to offer treatment after a full explanation, particularly because
      treatment is generally prescribed in the antiphospholipid syndrome and justified
      in hereditary thrombophilias according to the report of Carp and colleagues,
      showing a 25% improvement in live birth rates in treated patients. When treatment
      fails, however, the embryo should be karyotyped to exclude chromosomal
      aberrations.

PMID- 16962920
TI  - Thrombophilia and adverse pregnancy outcome.
AB  - This article focuses on the clinical evaluation and management of women who have
      thrombophilia-related placental vascular complications, including fetal loss, pre
      eclampsia, intrauterine fetal growth restriction, and placental abruption. All
      are major causes of maternal and fetal adverse outcomes.

PMID- 16962921
TI  - Fetal and neonatal thrombophilia.
AB  - Thrombophilia of the fetus and neonate may contribute to higher prevalence of
      perinatal thrombosis. Due to the potential interaction between thrombophilic risk
      factors of the neonate and maternal thrombophilia and placental vasculopathy, we
      recommend thrombophilia assessment be performed in any child and in the mother in
      case of perinatal thrombosis. Further attention and larger prospective studies
      are required to establish the role of thrombophilic risk factors in the
      pathogenesis of any other perinatal complications.

PMID- 16962922
TI  - Exogenous sex hormones and thrombophilia.
AB  - Worldwide, hundreds of millions of women use exogenous estrogens in
      contraceptives or for postmenopausal hormone replacement. Exogenous estrogens
      increase the risk for venous and arterial thrombosis. This article reviews the
      use of exogenous sex hormones in women with thrombophilia.

PMID- 16962923
TI  - The obstetrical patient with a prosthetic heart valve.
AB  - Definitive recommendations on anticoagulation strategy in pregnant women who have
      prosthetic heart valves are lacking because of the paucity of prospectively
      collected data. The use of warfarin, UFH, LMWH, or any combination of these
      choices has potentially adverse outcomes for the mother and fetus. Although there
      is no treatment option that has proven to be completely satisfactory, there is
      agreement that failures are most often due to underdosing and the lack of
      intensive monitoring of anticoagulation. A careful discussion with the patient
      must be undertaken so that she and the clinician can come to a decision about the
      most appropriate protocol.

PMID- 16962924
TI  - Peripartum and perioperative management of the anticoagulated patient.
AB  - Management of the pregnant patient requiring anticoagulation in the peripartum
      period represents a significant clinical challenge. The peripartum period
      includes the most thrombogenic pregnancy-associated state and the intrapartum and
      immediate postpartum periods, when hemorrhage is and important concern. Clinical
      decisions depend on the type of antepartum anticoagulation, obstetric factors,
      risk of hemorrhage, and the risk and implications of thrombosis.

PMID- 16962925
TI  - The Seventh American College of Chest Physicians Guidelines for the antenatal and
      peripartum management of thrombophilia: A tutorial.
AB  - The latest guidelines for the prevention of venous thromboembolism were published
      by the American College of Chest Physicians in September 2004. This set of
      updated guidelines represents a discussion of treatments of venous thrombosis,
      thromboprophylaxis, and revision of those published in 2001. These guidelines
      propose some "official" recommendations for health-care providers for women
      during the peripartum period. The purpose of this article is to settle some
      ambiguity and to present these recommendations in a clinical format.

PMID- 16962926
TI  - Lung carcinogenesis: pivotal role of metals in tobacco smoke.
AB  - Although significant progress has been made in unraveling the molecular
      mechanisms responsible for tobacco smoke toxicity and carcinogenicity, only
      limited information is available concerning the mechanisms by which tar particles
      and the gaseous phase constituents of tobacco smoke participate and contribute to
      carcinogenic processes in lung cancer. The present review critically evaluates
      how metals contained in the tar particles and the gaseous phase of tobacco smoke
      play a leading role in the carcinogenic process, taking into consideration the
      physiology and pathophysiology of the bronchial epithelium. Overwhelmingly, the
      published data indicate that the bronchopulmonary epithelial cells may represent
      the first and most critical line of defense against cigarette smoke.

PMID- 16962927
TI  - Antioxidant and cytoprotective properties of high-density lipoproteins in
      vascular cells.
AB  - Beside their key role in the regulation of cholesterol homeostasis, HDL exhibit
      antioxidant and anti-inflammatory properties that participate to their general
      antiatherogenic effect. The purpose of this review is to summarize the recent
      findings on antioxidant activity and cytoprotective cell signalling elicited by
      HDL against oxidized LDL and proatherogenic agents in vascular cells. HDL exhibit
      an antioxidant activity efficient to prevent LDL oxidation, or to inactivate
      newly formed lipid oxidation products. The antioxidant ability of HDL is due to
      the apoprotein moiety and to the presence of associated enzymes, paraoxonase and
      PAF-Acetyl Hydrolase. HDL prevent the intracellular oxidative stress and the
      inflammatory response elicited by oxidized LDL (ox-LDL), by inhibiting the
      NFkappaB signalling pathway, and the subsequent inflammatory events (expression
      of adhesion molecules, recruitment and proliferation of mononuclear cells within
      the vascular wall). HDL prevent ox-LDL-mediated cell activation and
      proliferation, this being also attributed to the presence in HDL of sphingosine-1
      phosphate which modulates the migration and survival of vascular cells. Lastly,
      HDL inhibit apoptosis elicited by ox-LDL in vascular cells. Recent evidences
      indicate that, beside their strong antiatherogenic properties, HDL could exert
      their protective effect in diseases generally associated to inflammatory events.

PMID- 16962928
TI  - A pharmacogenomic study of atorvastatin effects on eNOS activity: do "statins"
      modulate blood nitrite levels and intravascular oxidant stress in susceptible
      individuals?

PMID- 16962929
TI  - eNOS gene T-786C polymorphism modulates atorvastatin-induced increase in blood
      nitrite.
AB  - Statins inhibit cholesterol synthesis and produce pleiotropic, cholesterol
      independent effects including endothelial NO synthase (eNOS) stimulation and
      increased expression. However, a functional polymorphism in the promoter of the
      eNOS gene (T-786C) reduces its activity and could modulate the response to
      statins. Here, we examined whether this polymorphism modulates the effects of
      atorvastatin on the plasma levels of markers of NO formation and oxidative
      stress. We genotyped 200 healthy subjects for this polymorphism, and 15 subjects
      with the TT genotype and 15 with the CC genotype were selected to receive placebo
      or atorvastatin 10 mg/day po for 14 days. To assess NO bioavailability, the
      plasma concentrations of nitrate, nitrite, and cGMP and the whole blood nitrite
      concentrations were determined after placebo or atorvastatin using an ozone-based
      chemiluminescence assay and an enzyme immunoassay. Thiobarbituric acid-reactive
      species (TBA-RS) were measured in the plasma to assess oxidative stress.
      Atorvastatin decreased cholesterol concentrations independent of genotype.
      Whereas atorvastatin produced no significant changes in plasma nitrite, nitrate,
      or cGMP concentrations in both genotype groups, atorvastatin increased whole
      blood nitrite concentrations and decreased plasma TBA-RS concentrations in the CC
      (but not in the TT) genotype group. These findings suggest that the T-786C
      polymorphism modulates the effects of atorvastatin on NO bioavailability and
      oxidative stress.

PMID- 16962930
TI  - The confounding effects of light, sonication, and Mn(III)TBAP on quantitation of
      superoxide using hydroethidine.
AB  - Previously, we showed that hydroethidine (HE) reacts with intracellular
      superoxide radical anion (O2-*) to form a unique fluorescent marker product, 2
      hydroxyethidium cation (2-OH-E+), that was not formed from HE reaction with other
      biologically relevant oxidants (H. Zhao et al. Proc. Natl. Acad. Sci. USA102:5727
      5732; 2005). Here we rigorously assessed the confounding effects of light,
      sonication, and Mn(III)TBAP on 2-OH-E+, the HE/O2-* reaction product. Results
      indicate that continuous exposure to visible light induced photo-oxidation of HE
      to ethidium cation (E+) by a 2-OH-E+ -dependent mechanism. Treatment of HE with
      ultrasound, a frequently used technique to lyse cell membranes, induced 2-OH-E+
      from in situ generation of O2-*. Mn(III)TBAP, a cell-permeable metal-porphyrin
      complex used as a catalytic antioxidant, reacts with HE to form E+. This finding
      provides an alternative interpretation for Mn(III)TBAP effects during the HE/O2-*
      reaction. In order to correctly interpret the HE reaction with O2-* in cells, it
      is therefore imperative that HE and HE-derived products be measured by HPLC. A
      new and improved HPLC-electrochemical (HPLC-EC) detection has been developed for
      analysis of intracellular O2-*. The HPLC-EC method is at least 10 times more
      sensitive than the HPLC-fluorescence technique for detecting O2-* in cells.

PMID- 16962931
TI  - PEP-1-SOD fusion protein efficiently protects against paraquat-induced
      dopaminergic neuron damage in a Parkinson disease mouse model.
AB  - Parkinson disease (PD) is a common neurodegenerative disorder characterized by
      the progressive loss of dopaminergic neurons in the substantia nigra (SN).
      However, the mechanism of the pathology of PD still remains poorly understood.
      Because the administration of the herbicide paraquat triggers selective
      dopaminergic neuronal cell death, exposure of mice to this herbicide is one
      valuable model for studying the pathological aspects of PD. In this study, we
      investigated the protective effects of PEP-1-SOD in vitro and in vivo under
      exposure to the herbicide paraquat. The viability of neuronal cells treated with
      paraquat was markedly increased by transduced PEP-1-SOD. When the PEP-1-SOD
      fusion protein was injected intraperitoneally into mice, a completely protective
      effect against dopaminergic neuronal cell death in the SN was observed. This
      protective effect was synergistically increased when the PEP-1-SOD was
      cotransduced with Tat-alpha-synuclein. These results suggest that PEP-1-SOD
      provides a strategy for therapeutic delivery in various human diseases related to
      reactive oxygen species, including PD.

PMID- 16962932
TI  - Alpha-tocopherol regulation of hepatic cytochrome P450s and ABC transporters in
      rats.
AB  - To test the hypothesis that supra-elevated hepatic alpha-tocopherol
      concentrations would up-regulate mechanisms that result in increased hepatic
      alpha-tocopherol metabolism and excretion, rats received daily subcutaneous alpha
      tocopherol injections (10 mg/100 g body wt) and then were sacrificed on Day 0 or
      12 h following their previous injection on Days 3, 6, 9, 12, 15, and 18. Liver
      alpha-tocopherol concentrations increased from 12 +/- 1 nmol/g (mean +/- SE) to
      819 +/- 74 (Day 3), decreased at Day 9 (486 +/- 67), and continued to decrease
      through Day 18 (338 +/- 37). alpha-Tocopherol metabolites and their intermediates
      increased and decreased similarly to alpha-tocopherol albeit at lower
      concentrations. There were no changes in known vitamin E regulatory proteins,
      i.e., hepatic alpha-tocopherol transfer protein or cytochrome P450 (CYP) 4F. In
      contrast, both CYP3A and CYP2B, key xenobiotic metabolizing enzymes, doubled by
      Day 6 and remained elevated, while P450 reductase increased more slowly.
      Consistent with the decrease in liver alpha-tocopherol concentrations, a protein
      involved in biliary xenobiotic excretion, p-glycoprotein, increased at Day 9,
      doubling by Day 15. Thus hepatic alpha-tocopherol concentrations altered hepatic
      proteins involved in metabolism and disposition of xenobiotic agents.

PMID- 16962933
TI  - Peroxynitrite induces HO-1 expression via PI3K/Akt-dependent activation of NF-E2
      related factor 2 in PC12 cells.
AB  - Peroxynitrite is a strong oxidant produced by rapid interaction between
      superoxide anion and nitric oxide radicals and induces oxidative stress and cell
      death. Treatment of PC12 cells with 3-morpholinosydnonimine (SIN-1), a generator
      of peroxynitrite, induced the expression of heme oxygenase-1 (HO-1), an
      antioxidant cytoprotective enzyme. Inhibition of the HO activity by zinc
      protoporphyrin IX or knockdown of HO-1 gene expression with siRNA exacerbated the
      SIN-1-induced apoptosis. After SIN-1 treatment, there was a time-related increase
      in nuclear localization and subsequent binding of NF-E2-related factor 2 (Nrf2)
      to the antioxidant-responsive element (ARE). Transfection of PC12 cells with
      dominant-negative Nrf2 abolished the SIN-1-induced increase in Nrf2-ARE binding
      and subsequent upregulation of HO-1 expression, leading to enhanced cell death.
      Upon exposure of PC12 cells to SIN-1, the phosphatidylinositol 3-kinase (PI3K)
      activity was increased in a time-dependent manner. Pretreatment of cells with
      LY294002, a pharmacologic inhibitor of PI3K or transfection with the kinase-dead
      mutant Akt abrogated the SIN-1-induced Nrf2 activation and HO-1 expression. Taken
      together, these results suggest that peroxynitrite activates Nrf2 via PI3K/Akt
      signaling and enhances Nrf2-ARE binding, which leads to upregulation of HO-1
      expression. The SIN-1-induced HO-1 upregulation may confer the adaptive survival
      response against nitrosative stress.

PMID- 16962934
TI  - Acute administration of vitamin E triggers preconditioning via K(ATP) channels
      and cyclic-GMP without inhibiting lipid peroxidation.
AB  - Vitamin E (VitE) is considered an antioxidant agent. One or more brief periods of
      ischemia (isc), followed by short reperfusion (rep), increase the tolerance of
      the heart to a subsequent prolonged ischemia, a phenomenon known as ischemic
      preconditioning (PC). Mitochondrial KATP channels (mitoKATP), cyclic-GMP (cGMP),
      and free radicals are involved in the mechanism of PC, whereas some antioxidants
      abolish this benefit. The purpose of this study was to evaluate the effect of
      VitE on infarct size, PC, and the oxidative status in vivo. Male rabbits were
      divided into seven groups and were subjected to myocardial ischemia (isc) and
      reperfusion (rep) with the following interventions: (1) control (no
      intervention); (2) E150 (iv VitE at a dose of 150 mg/kg for 75 min, starting 40
      min before index isc and lasting through 5 min of rep); (3) E300 (iv VitE 300
      mg/kg as previously described); (4) PC (two cycles of 5 min isc and 10 min rep),
      (5) combined E150-PC; and (6) combined E300-PC. In the last two groups VitE was
      given 40 min before index ischemia. Blood samples were taken for malondialdehyde
      (MDA) and conjugated dienes (CDs) measurement. In a second series of experiments
      heart tissue samples were taken at the time of long ischemia for MDA and CD
      determination and for cGMP assay. In order to test whether combined treatment
      with VitE (as the E150 group) and the mitoKATP blocker 5-hydroxydecanoic acid (5
      HD) changes the infarct size, an additional group was assessed in the first
      series of experiments. Tissue VitE concentration was evaluated in myocardium.
      VitE at both doses reduced the infarct size (19.7 +/- 2.8% for E150 and 18.8 +/-
      4.9% for E300 vs 47.4 +/- 2.6% in control, P < 0.05) without attenuating the
      effect of PC (10.2 +/- 3.1% for E150-PC, 12.4 +/- 2.2% for E300-PC, vs 13.5 +/-
      3.3% for PC). Combined VitE and 5-HD treatment abrogates this benefit (37.4 +/-
      6.5%, P < 0.05 vs E150 and NS vs control). VitE increases intracellular cGMP and
      CDs levels (P < 0.05 vs control) to the same extent as PC (P < 0.05 vs control),
      with no effect on MDA (P = NS between all the groups). Peripheral markers of
      oxidative stress are increased during reperfusion in all groups (P < 0.05 vs
      baseline). Overall, VitE limits infarct size via mitoKATP and cGMP, while
      preserving the benefit of ischemic PC.

PMID- 16962935
TI  - Increased toxicity by transforming growth factor-beta 1 in liver cells
      overexpressing CYP2E1.
AB  - Ethanol treatment causes an increase in expression of TGF-beta1 and CYP2E1 in the
      centrilobular area. Alcoholic liver disease is usually initiated in the
      centrilobular region of the liver. We hypothesized that the combination of TGF
      beta1 and CYP2E1 produces increased oxidative stress and liver cell toxicity. To
      test this possibility, we studied the effects of TGF-beta1 on the viability of
      HepG2 E47 cells that express human CYP2E1, and C34 HepG2 cells, which do not
      express CYP2E1. E47 cells underwent greater growth inhibition and enhanced
      apoptosis after TGF-beta1 treatment, as compared to the C34 cells. There was an
      enhanced production of reactive oxygen species (ROS) and a decline in reduced
      glutathione (GSH) levels in the TGF-beta1-treated E47 cells and the enhanced cell
      death could be prevented by antioxidants. The CYP2E1 inhibitor diallyl sulfide
      prevented the potentiated cell death in E47 cells validating the role of CYP2E1.
      Mitochondrial membrane potential declined in the TGF-beta1-treated E47 cells,
      prior to developing toxicity, and cell death could be prevented by
      trifluoperazine, an inhibitor of the mitochondrial membrane permeability
      transition. TGF-beta1 also produced a loss of cell viability in hepatocytes from
      pyrazole-treated rats with elevated levels of CYP2E1, compared to control
      hepatocytes. In conclusion, increased toxic interactions by TGF-beta1 plus CYP2E1
      can occur by a mechanism involving increased production of intracellular ROS and
      depletion of GSH, resulting in mitochondrial membrane damage and loss of membrane
      potential, followed by apoptosis. Potentiation of TGF-beta1-induced cell death by
      CYP2E1 may contribute to mechanisms of alcohol-induced liver disease.

PMID- 16962936
TI  - Cooperative activity of Ref-1/APE and ERp57 in reductive activation of
      transcription factors.
AB  - ERp57, a protein disulfide isomerase localized mainly in the endoplasmic
      reticulum, has also been found in lesser amounts in the cytosol and nucleus,
      where its function is still not characterized. We report here that ERp57 displays
      affinity for Ref-1, a protein involved in DNA repair as well as in the reduction
      and activation of transcription factors. Immunoprecipitation experiments showed
      that Ref-1 and ERp57 also interact in vivo in at least three types of cultured
      human cells, namely HepG2, M14, and Raji. Oxidative stress increased the amount
      of nuclear Ref-1 associated with ERp57. Moreover, ERp57 reduced by the
      thioredoxin-reductase/thioredoxin system stimulated the binding of AP-1 to its
      consensus sequence on DNA, and HeLa cells stably transfected and overexpressing
      ERp57 were protected against hydrogen peroxide-induced cell killing. Accordingly,
      ERp57 appears to cooperate with Ref-1 in the regulation of gene expression
      mediated by redox-sensitive transcription factors and in the adaptive response of
      the cell to oxidative insult.

PMID- 16962937
TI  - Systematic study on ROS production induced by oleic, linoleic, and gamma
      linolenic acids in human and rat neutrophils.
AB  - The effects of oleic, linoleic, and gamma-linolenic acids on the production of
      ROS by unstimulated and PMA-stimulated neutrophils were investigated by using
      five techniques: luminol- and lucigenin-amplified chemiluminescence, cytochrome
      c, hydroethidine, and phenol red reduction. Using lucigenin-amplified
      chemiluminescence, an increase in extracellular superoxide levels was observed by
      the treatment of neutrophils with the fatty acids. There was also an increase in
      intracellular ROS levels under similar conditions as measured by the
      hydroethidine technique. An increment in the intra- and extracellular levels of
      H2O2 was also observed in neutrophils treated with oleic acid as measured by
      phenol red reduction assay. In the luminol technique, peroxidase activity is
      required in the reaction of luminol with ROS for light generation. Oleic,
      linoleic, and gamma-linolenic acids inhibited the myeloperoxidase activity in
      stimulated neutrophils. So, these fatty acids jeopardize the results of ROS
      content measured by this technique. Oleic, linoleic, and gamma-linolenic acids
      per se led to cytochrome c reduction and so this method also cannot be used to
      measure ROS production induced by fatty acids. Oleic, linoleic, and gamma
      linolenic acids do stimulate ROS production by neutrophils; however, measurements
      using the luminol-amplified chemiluminescence and cytochrome c reduction
      techniques require further analysis.

PMID- 16962938
TI  - Effect of dietary virgin olive oil on urinary excretion of etheno-DNA adducts.
AB  - A significant protective effect against cancer and coronary heart disease has
      been attributed to the Mediterranean diet, in which olive oil is the main source
      of fat. Dietary antioxidants, as phenolic compounds from virgin olive oil, are
      candidates for reducing cancer risk by minimizing oxidatively derived DNA damage.
      Etheno-DNA adducts are formed as a result of oxidative stress and lipid
      peroxidation. To evaluate whether phenol-rich virgin olive oil influences urinary
      excretion of the etheno-DNA adducts epsilonAde, epsilondA, and epsilondC as
      markers of oxidative stress, a randomized, double-blinded, crossover trial with
      three intervention periods was conducted in 28 healthy men. Each intervention was
      of 3 weeks' duration and separated by 2-week washout periods. Twenty-five
      milliliters of similar olive oils, but with differences in their phenolic content
      (from 2.7 to 366 mg/kg), were supplied to each subject per day. The urinary
      excretion of the DNA adducts was assayed by LC-MS/MS in samples before and after
      consumption of high phenolic content olive oil (virgin). The 24-h excretion rate
      did not differ significantly between baseline and after virgin olive oil
      consumption: epsilonAde, 105.5 +/- 40.8 vs 116.4 +/- 53.4 pmol epsilonAde/24 h (p
      = 0.21); epsilondA, 37.9 +/- 24.8 vs 37.6 17 +/- 24.2 pmol epsilondA/24 h (p =
      0.93); and epsilondC, 218.7 +/- 157.2 vs 193.5 +/- 64.7 pmol epsilondC/24 h (p =
      0.37). Multiple regression analysis showed a significant association between
      etheno-DNA adduct excretion rate and the dietary intake of linoleic acid (C18:2,
      omega-6) in healthy men. Consumption of 25 ml per day of phenol-rich virgin olive
      oil for 3 weeks did not modify to a significant degree the urinary excretion of
      etheno-DNA adducts in 28 healthy volunteers.

PMID- 16962939
TI  - Cytotoxicity of myeloperoxidase/nitrite-oxidized low-density lipoprotein toward
      endothelial cells is due to a high 7beta-hydroxycholesterol to 7-ketocholesterol
      ratio.
AB  - Oxygenated cholesterols (oxysterols) formed during oxidation of low-density
      lipoprotein (LDL) are associated with endothelial dysfunction and atherogenesis.
      We compared the profile of oxysterols in modified human LDL obtained on reaction
      with myeloperoxidase/H2O2 plus nitrite (MPO/H2O2/nitrite-oxLDL) with that on Cu2+
      -catalyzed oxidation. The 7beta-hydroxycholesterol/7-ketocholesterol ratio was
      markedly higher in MPO/H2O2/nitrite-oxLDL than in Cu2+ -oxidized LDL (7.9 +/- 3.0
      versus 0.94 +/- 0.10). Like MPO/H2O2/nitrite-oxLDL, 7beta-hydroxycholesterol was
      cytotoxic toward endothelial cells through eliciting oxidative stress.
      Cytotoxicity was accompanied by DNA fragmentation and was prevented by the NADPH
      oxidase inhibitor apocynin, suggesting stimulation of NADPH oxidase-mediated O2-*
      formation. 7-Ketocholesterol was only cytotoxic when added alone, whereas a 1:1
      mixture with 7beta-hydroxycholesterol surprisingly was noncytotoxic. We conclude
      from our data that (i) 7beta-hydroxycholesterol is a pivotal cytotoxic component
      of oxidized LDL, (ii) 7-ketocholesterol protects against 7beta-hydroxycholesterol
      in oxysterol mixtures or oxLDL, (iii) the 7beta-hydroxycholesterol/7
      ketocholesterol ratio is a crucial determinant for cytotoxicity of oxidized LDL
      species and oxysterol mixtures, and (iv) the low share of 7-ketocholesterol
      explains the higher cytotoxicity of MPO/H2O2/nitrite-oxLDL than other forms of
      oxidized LDL. The dietary polyphenol (-)-epicatechin inhibited not only formation
      but also cytotoxic actions of both oxLDL and oxysterols.

PMID- 16962940
TI  - Transferrin inhibits stress-induced apoptosis in a beetle.
AB  - Transferrin in insects is known as an iron transporter, an antibiotic agent, a
      vitellogenin, and a juvenile hormone-regulated protein. We show here a novel
      functional role for insect transferrin. Stresses, such as iron overload,
      bacterial or fungal challenge, cold or heat shock, wounding, and H2O2 or paraquat
      exposure, cause upregulation of the beetle Apriona germari transferrin (AgTf)
      gene in the fat body and epidermis, and they cause increased AgTf protein levels.
      RNA interference (RNAi)-mediated AgTf reduction results in rapid induction of
      apoptotic cell death in the fat body during exposure to heat stress. The observed
      effect of AgTf RNAi indicates that AgTf inhibits heat stress-induced apoptotic
      cell death, suggesting a functional role for AgTf in defense and stress responses
      in the beetle.

PMID- 16962941
TI  - Nitric oxide modulates Gi-protein expression and adenylyl cyclase signaling in
      vascular smooth muscle cells.
AB  - We have previously shown that treatment of rats with the nitric oxide (NO)
      synthase inhibitor N6-nitro-L-arginine methyl ester for 4 weeks resulted in the
      augmentation of blood pressure and enhanced levels of Gialpha proteins. The
      present studies were undertaken to investigate if NO can modulate the expression
      of Gi proteins and associated adenylyl cyclase signaling. A10 vascular smooth
      muscle cells (VSMC) and primary cultured cells from aorta of Sprague-Dawley rats
      were used for these studies. The cells were treated with S-nitroso-N
      acetylpenicillamine (SNAP) or sodium nitroprusside (SNP) for 24 h and the
      expression of Gialpha proteins was determined by immunobloting techniques.
      Adenylyl cyclase activity was determined by measuring [32P]cAMP formation for
      [alpha-32P]ATP. Treatment of cells with SNAP (100 microM) or SNP (0.5 mM)
      decreased the expression of Gialpha-2 and Gialpha-3 by about 25-40% without
      affecting the levels of Gsalpha proteins. The decreased expression of Gialpha
      proteins was reflected in decreased Gi functions (receptor-independent and 
      dependent) as demonstrated by decreased or attenuated forskolin-stimulated
      adenylyl cyclase activity by GTPgammaS and inhibition of adenylyl cyclase
      activity by angiotensin II and C-ANP4-23, a ring-deleted analog of atrial
      natriuretic peptide (ANP) that specifically interacts with natriuretic peptide
      receptor-C (NPR-C) in SNAP-treated cells. The SNAP-induced decreased expression
      of Gialpha-2 and Gialpha-3 proteins was not blocked by 1H[1,2,4]oxadiazole[4,3
      a]quinoxalin-1-one, an inhibitor of soluble guanylyl cyclase, or KT5823, an
      inhibitor of protein kinase G, but was restored toward control levels by uric
      acid, a scavenger of peroxynitrite and Mn(111)tetralis (benzoic acid porphyrin)
      MnTBAP, a peroxynitrite scavenger and a superoxide dismutase mimetic agent that
      inhibits the production of peroxynitrite, suggesting that NO-mediated decreased
      expression of Gialpha protein was cGMP-independent and may be attributed to
      increased levels of peroxynitrite. In addition, Gsalpha-mediated stimulation of
      adenylyl cyclase by GTPgammaS, isoproterenol, and forskolin was significantly
      augmented in SNAP-treated cells. These results indicate that NO decreased the
      expression of Gialpha protein and associated functions in VSMC by cGMP
      independent mechanisms. From these studies, it can be suggested that NO-induced
      decreased levels of Gi proteins and resultant increased levels of cAMP may be an
      additional mechanism through which NO regulates blood pressure.

PMID- 16962942
TI  - Glutathione-peroxidase-1 null muscle progenitor cells are globally defective.
AB  - Mice lacking glutathione peroxidase-1 (Gpx1) have decreased resistance to
      systemically administered oxidants as well as infections, and sustain increased
      damage after ischemia-reperfusion injuries. However, stem or progenitor cell
      function in these animals has not been studied. We characterized patterns of
      proliferation, apoptosis, and differentiation of primary muscle progenitor cells
      (myoblasts) from Gpx1(-/-) mice. Myoblasts are the transit amplifying compartment
      of skeletal muscle. All aspects of myoblast biology are negatively affected by
      deletion of Gpx1. In particular, passaged, proliferating Gpx1(-/-) myoblasts,
      when induced to differentiate into fused multinucleated myotubes, show
      significant impairment, and form only a few immature myotubes. This defect occurs
      despite increased expression of the core regulators of muscle differentiation,
      the myogenic basic helix-loop-helix (bHLH) transcription factors, in the Gpx1(-/
      ) myoblasts. Furthermore, Gpx1(-/-) myoblasts exhibited decreased proliferation
      and increased apoptosis compared to wild-type cells. In vivo, muscle fiber areas
      are decreased in Gpx1(-/-) vs wild-type mice. These data suggest that Gpx1 is
      important for adult muscle progenitor cell function at many levels, is necessary
      for integrity of muscle differentiation, and that quiescent resident stem cell
      populations may be particularly vulnerable to peroxide-mediated damage.

PMID- 16962943
TI  - The hateful patient revisited: Relevance for 21st century medicine.
AB  - While the practice of medicine has changed over the years, including
      technological advances, access to medical information, and the narrowing of socio
      economic and educational gaps between the clinician and his/her patients, the
      importance of the doctor-patient relationship has not diminished over time. This
      can be a very rewarding interaction. However, many physicians experience a great
      deal of anger, inadequacy and frustration, and much of the actual practice of
      medicine may become a burden rather than a source of satisfaction. Physicians may
      encounter a subset of patients who engender strong negative feelings, despair and
      even downright malice. An understanding of the "hateful patient" can therefore be
      very informative to the physician. Several categories of such patients may be
      described, and sensitivity to the phenomenon will lead to improved physician well
      being, less self-destructive patient behavior and a lower risk of litigation.
      Several factors may assist the 21st century physician in managing the "hateful
      patient" in an empathic manner and in making some sense of why the patient has
      resorted to negative response patterns. Ultimately, a failure to consider these
      issues will result in poorer medical care and, no less important, reduced
      satisfaction of both patients and doctors. The intention of this article is to
      revisit the concept and to place it in the context of contemporary medical
      practice.

PMID- 16962944
TI  - An update on the etiology and diagnostic evaluation of a leukemoid reaction.
AB  - Persistent neutrophilic leukocytosis above 50,000 cells/muL when the cause is
      other than leukemia defines a leukemoid reaction. The diagnostic work-up consists
      of the exclusion of chronic myelogenous leukemia (CML) and chronic neutrophilic
      leukemia (CNL) and the detection of an underlying cause. The major causes of
      leukemoid reactions are severe infections, intoxications, malignancies, severe
      hemorrhage, or acute hemolysis. The present article points out the difficulties
      in the differential diagnosis of a leukemoid reaction and suggests an algorithm
      for a rational clinical and laboratory evaluation of this problematic entity.

PMID- 16962945
TI  - Mentoring in internal medicine.
AB  - Mentoring is a relationship aimed at fostering the development of the less
      experienced person. The internal medicine community has recently recognized the
      importance of this relationship in the advancement of careers in the profession.
      Preliminary evidence points to the importance of mentoring in achieving the
      mentee's goals without much suggestion that it could be harmful. It can be
      particularly helpful to women and minority junior faculty. We encourage academic
      institutions to help forge these relationships by developing their own formal
      systems of mentoring and to evaluate and report their efforts.

PMID- 16962946
TI  - Hospital at home for acute respiratory patients.
AB  - BACKGROUND: The issue of "hospital at home" (HAH) for acute respiratory patients
      is one that is still being debated, partly because economic, cultural and health
      service differences between locations imply that HAH schemes need to be tailored
      to local situations. The aim of the present study was to analyze the feasibility
      and effectiveness of HAH for patients with acute respiratory disease at our
      institution. METHODS: Of all the patients admitted to our institution via the
      emergency department during a 34-day subject enrollment period, 25 with diagnoses
      of respiratory infection, pneumonia, pulmonary insufficiency or exacerbated
      chronic obstructive pulmonary disease who were living within 25 km of our center
      and who were willing to receive HAH care were assigned to HAH. Fifty sex-matched
      controls with the same diagnoses were given conventional hospital care (CHC) as
      inpatients. The dependent variables evaluated included time to discharge,
      readmissions within 3 months and deaths within 3 months. RESULTS: There were no
      significant differences between the HAH and CHC groups with regard to age,
      diagnoses, physical and analytical findings, or co-morbidity, or with regard to
      deaths (HAH 16%, CHC 10%) or readmissions (HAH 17%, CHC 24%). Time to final
      discharge was significantly shorter for HAH patients (7 days) than for CHC
      patients (12 days). Some 95% of the HAH patients were satisfied and would choose
      HAH again. CONCLUSIONS: HAH seems feasible for appropriately selected acute
      respiratory disease patients presenting in our emergency department. It frees
      hospital beds for other patients, its readmission and mortality rates are no
      higher than for conventional hospitalization, and, in general, it is favorably
      evaluated by patients.

PMID- 16962947
TI  - PTHrP and insulin levels following oral glucose and calcium administration.
AB  - BACKGROUND: Parathyroid hormone-related peptide (PTHrP), identified as a tumor
      product, is responsible for humoral malignant hypercalcemia. Unlike PTH, PTHrP is
      found in almost every body tissue including pancreatic alpha, beta, delta, and pp
      cells, where it is processed into multiple secretory forms, co-packaged with
      insulin, and secreted in a regulated fashion in response to insulin
      secretagogues. Ionized calcium is a stimulator for the release of several peptide
      hormones. METHODS: In the present study, we examined the effect of an oral
      calcium (1 g elemental calcium) and glucose (75 g) load on insulin and PTHrP
      release in 16 healthy volunteers and of an oral calcium load in 16 non-insulin
      dependent diabetes mellitus (NIDDM) patients. Serum calcium, glucose, insulin,
      and PTHrP levels were determined at 0, 5, 10, 15, 30, and 60 min. RESULTS: Our
      results indicate that, at each time point, type 2 diabetic patients exhibited
      greater basal values of PTHrP than controls (200.3+/-110.5 pg/ml vs. 82.0+/-22.3
      pg/ml, respectively, p<0.0001). The PTHrP level was consistently higher in
      response to the glucose load than the calcium load at each time point observed
      (p<0.0001). NIDDM patients exhibited greater basal serum PTHrP levels than the
      control group. CONCLUSION: PTHrP was proven for the first time to be released
      from beta cells in parallel to insulin and in response to glucose stimulation.

PMID- 16962948
TI  - Serum interleukin-17 and its relationship to angiogenic factors in multiple
      myeloma.
AB  - BACKGROUND: Interleukin-17 (IL-17) is a CD4 T-cell-derived mediator of
      angiogenesis that stimulates vascular endothelial cell migration and regulates
      the production of a variety of proangiogenic factors, such as tumor necrosis
      factor-alpha (TNF-alpha) and vascular endothelial cell growth factor (VEGF).
      Angiogenesis is implicated in the progression of multiple myeloma (MM). METHODS:
      We measured serum levels of IL-17, TNF-alpha, and VEGF, as well as microvessel
      density (MVD) in 40 untreated MM patients. RESULTS: Levels of IL-17 in the sera
      of patients with MM were higher than those in matched controls; however, the
      difference did not reach statistical significance. Serum levels of both TNF-alpha
      and VEGF in MM patients were significantly higher than those in controls (p<0.001
      in both instances). Levels of IL-17 in MM patients, both stage II and stage III,
      were significantly higher than those of stage I patients (p=0.001 and p<0.001,
      respectively). Similarly, higher values of VEGF (p<0.001), TNF-alpha (p<0.001),
      and MVD (p<0.035) were associated with advanced disease stage. Serum values of IL
      17 in MM patients correlated positively not only with VEGF (Spearman's rho=0.606)
      and TNF-alpha (r=0.552; p<0.001 in both instances), but also with MVD (r=0.385,
      p=0.014). In addition, a positive correlation was found between serum values of
      VEGF and TNF-alpha (r=0.657, p<0.001), MVD and VEGF (r=0.353, p=0.026), and
      between MVD and TNF-alpha (r=0.506, p=0.001) in MM patients. CONCLUSION: These
      results suggest that IL-17 plays a role in the promotion of angiogenesis and
      associated disease progression in MM.

PMID- 16962949
TI  - Characteristic findings on 24-h ambulatory blood pressure monitoring in a series
      of patients with Parkinson's disease.
AB  - BACKGROUND: Patients with Parkinson's disease frequently present with orthostatic
      hypotension, prompting testing with 24-h ambulatory blood pressure monitoring
      (ABPM). The aim of our study was to identify characteristic patterns of blood
      pressure changes present on ABPM in a series of patients with Parkinson's
      disease. METHOD: We retrospectively identified 13 patients with Parkinson's
      disease who had undergone ABPM for evaluation of symptomatic orthostatic
      hypotension. The ABPM tracings were analyzed for the presence or absence of
      reversal of circadian pattern, postprandial hypotension, noncompensatory heart
      rate variability, and average daytime and nocturnal blood pressure values.
      RESULTS: Reversal of circadian rhythm was identified in 92.3%, postprandial
      hypotension in 100% and nocturnal hypertension in 100% of the cases. Some 61.5%
      of the patients exhibited daytime blood pressures in the prehypertensive range,
      and 23% had blood pressures in the stage 1 hypertension range per JNC 7
      classification. CONCLUSION: The characteristic findings on 24-h ABPM in this
      series of patients with Parkinson's disease were the presence of reversal of
      circadian rhythm (93%), postprandial hypotension (100%) and nocturnal
      hypertension (100%).

PMID- 16962950
TI  - Quality of life in patients with active sarcoidosis in Greece.
AB  - BACKGROUND: The health status of patients with sarcoidosis has rarely been
      studied, despite the increasing numbers of health-related quality of life
      publications on other respiratory diseases. The aim of this cross-sectional study
      was to investigate whether sarcoidosis affects quality of life (QoL), using
      specifically designed questionnaires for respiratory diseases as well as general
      health measures, and to compare these with pulmonary function indices. Our
      secondary aim was to determine whether these measurements are correlated with
      pulmonary function tests and duration of the disease. METHODS: Included in the
      study were 75 consecutive patients with histologically confirmed active
      sarcoidosis. Self-completed dyspnea scales (Borg's scale, oxygen cost diagram,
      modified MRC questionnaire) and health-related quality of life (HRQoL)
      questionnaires (St George's Respiratory Questionnaire, Quality of Well-Being, and
      Anxiety and Depression) were used. Pulmonary function tests, measurements of
      arterial blood gases at rest and after exercise, chest radiographs, and duration
      of disease were used for correlation. RESULTS: We found that QoL was affected in
      sarcoidosis patients in comparison with healthy controls. Secondly, we found that
      the duration of the disease was correlated with all three dyspnea scales under
      evaluation, as well as with the SGRQ questionnaire. Furthermore, a significant
      correlation was shown between lung function tests (FVC, % pred and FEV(1), %
      pred) and both the BORG dyspnea scale and the SGRQ questionnaire. CONCLUSION:
      Quality of life is affected in patients with active sarcoidosis. The SGRQ
      questionnaire could be a useful tool for the investigation of HRQoL in an active
      sarcoid population with varying degrees of lung function impairment. Future
      studies are needed to address the ability of these instruments to measure HRQoL
      in the course of this chronic disease.

PMID- 16962951
TI  - Tuberculosis treatment duration in France: From guidelines to daily practice.
AB  - BACKGROUND: Guidelines for tuberculosis (TB) recommend 6 months of treatment
      except for meningeal TB, where a 9- to 12-month course may be preferred. METHODS:
      In order to assess whether practices in France are in agreement with those
      guidelines, we performed an anonymous audit of the policy of French physicians,
      focusing on TB treatment duration and corticosteroid use according to the TB
      presentation. RESULTS: Sixty-six completed forms were analyzed. Reported
      treatment duration was usually 6 months for pulmonary TB (91% of physicians) and
      miliary TB (45%), 9 months for pulmonary TB in HIV-infected patients (42%) and
      for TB lymphadenitis (57%), and 12 months for TB meningitis (79%) and osteo
      articular TB (65%). Corticosteroid use was systematic for meningitis (80%) and
      pericarditis (65%). CONCLUSION: This study reveals discrepancies between
      guidelines and daily practice for TB treatment duration in France: We observed a
      very high reported rate of unnecessary, prolonged treatment for most
      extrapulmonary TB.

PMID- 16962952
TI  - Extremely elevated C-reactive protein.
AB  - BACKGROUND: C-reactive protein (CRP) is a widely used inflammatory marker. Yet,
      the clinical significance and outcome of extremely elevated CRP levels are poorly
      characterized. METHODS: We collected all patients seen at a university hospital
      in 2004 with at least one CRP level above 500 mg/l and retrospectively analyzed
      their electronic files, focusing on patient characteristics, clinical diagnosis,
      microbiology and vital outcome. RESULTS: CRP was above 500 mg/l in 130 patients
      with a median age of 62 years. Patient characteristics, settings, etiologies of
      inflammation, comorbidities and microbiology varied widely. Infections, mainly
      bacterial, accounted for 88% of episodes. Outcome was fatal in 36% of all
      patients and in 61% of patients with active malignancies. CONCLUSION: A wide
      variety of infections, especially bacterial, that are generally readily
      identified account for the majority of instances of extreme CRP elevation.
      Mortality is high, certainly in oncological patients.

PMID- 16962953
TI  - FLT3/D835 mutation and inversion of chromosome 16 in leukemic transformation of
      myelofibrosis.
AB  - We present an atypical case of myelofibrosis developing into secondary leukemia
      FAB subtype M4, with inversion of chromosome 16, FLT3/D835 point mutation and
      diffuse osteolytic lesions accompanied by elevated TNF-alpha. The simultaneous
      occurrence of these mutations reflects the progressive association of genetic
      lesions developing into secondary leukemia with a relatively benign course.

PMID- 16962954
TI  - Tumoral calcinosis: Clinical and biochemical aspects of a patient treated with
      vinpocetine.
AB  - We describe a tumoral calcinosis (TC) patient with a calcified mass around the
      hip joint. Once diagnosed, she was followed up with vinpocetine [14
      ethoxycarbonyl-(3alpha,16alpha-ethyl)/14,15-eburnamenine] treatment, which was
      reported to be effective in eliminating TC in a previous study. We think that
      vinpocetine contributed, at least in part, to the process of TC elimination.
      Although there are many reports about the surgical excision of calcified masses
      in TC, local recurrences are not uncommon. Our success with conservative
      treatment has encouraged us to refrain from surgical procedures in patients with
      TC.

PMID- 16962955
TI  - Successful treatment of prolonged agranulocytosis caused by acute parvovirus B19
      infection with intravenous immunoglobulins.
AB  - A 21-year-old previously healthy male presented with prolonged fever of 3 weeks
      duration and profound agranulocytosis that did not respond to treatment with
      granulocyte-stimulating factors. A bone marrow biopsy demonstrated an absence of
      myeloid lineage. Acute parvovirus B19 infection was diagnosed by the presence of
      both IgM and IgG anti-parvovirus antibodies. Two days treatment with intravenous
      immunoglobulins (IVIg) resulted in complete recovery. The role of treatment with
      immunoglobulins in acute and persistent parvovirus infection is discussed.

PMID- 16962956
TI  - Bartonella quintana prosthetic valve endocarditis detected by blood culture
      incubation beyond 10 days.
AB  - We describe the case of a 45-year-old man with mitral and aortic prosthetic valve
      replacement who presented with symptoms of subacute bacterial endocarditis.
      Bartonella quintana was grown from blood after prolonged culture. The course of
      the disease was complicated by splenic infarction, glomerulonephritis resulting
      in progressive renal insufficiency, and cerebroventricular hemorrhage. Notably,
      cardiac ultrasonography showed no extensive vegetations but a strand-like lesion.
      Culture-positive B. quintana prosthetic valve endocarditis in a formerly healthy
      subject represents a newly observed entity. It should be added to the
      differential diagnosis of prosthetic valve endocarditis, especially when it
      presents with features suggesting subacute bacterial endocarditis.

PMID- 16962957
TI  - Can the routine use of fluoroquinolones for community-acquired pneumonia delay
      the diagnosis of tuberculosis? A salutary case of diagnostic delay in a pilgrim
      returning from Mecca.
AB  - Guidelines advocate using fluoroquinolones as first-line treatment for community
      acquired pneumonia (CAP). However, the use of fluoroquinolones in patients with
      undiagnosed tuberculosis may cause a delay in the diagnosis of tuberculosis and
      may also promote the development of resistance to these drugs if used as
      monotherapy in undiagnosed tuberculosis. We illustrate the former with the
      following case report of a patient who developed tuberculosis after a pilgrimage
      to Mecca.

PMID- 16962958
TI  - Novel 1113delC menin gene mutation in a Polish family with multiple endocrine
      neoplasia type 1 syndrome.
AB  - We report the case of a 32-year-old male with hypercalcemia and recurrent
      nephrolithiasis as a symptom of primary hyperparathyroidism, hypoglycemia due to
      insulinoma, microprolactinoma, and a large, partially calcified tumor of the
      upper right leg. The patient underwent several surgical interventions including
      subtotal parathyreoidectomy, partial pancreatectomy, and percutaneous
      nephrolithotrypsy. Regular treatment with bromocriptine was required for
      normalization of serum prolactin concentration. His only sibling, a 26-year-old
      sister, suffered from microprolactinoma and had been treated with bromocriptine
      for 6 years. Their father had suffered from recurrent kidney stones and peptic
      ulcer and died at the age of 34. A novel 1113delC mutation within exon 7 of the
      menin gene was found in both siblings. This mutation results in a frame-shift
      with missense translation of the subsequent residual acids and preterm
      termination of the peptide at codon 357.

PMID- 16962959
TI  - Eosinophilic pleural effusion caused by simvastatin after 13 years of exposure.

PMID- 16962960
TI  - Cutaneous metastasis of unusual cause.

PMID- 16962961
TI  - A non-healing foot ulcer in a patient with type 2 diabetes mellitus.

PMID- 16962962
TI  - Human infections with Fusobacterium necrophorum.
AB  - Fusobacterium necrophorum is a Gram-negative anaerobic bacillus that can be a
      primary pathogen causing either localised abscesses and throat infections or
      systemic life-threatening disease. Systemic infections due to F. necrophorum are
      referred to as either Lemierre's disease/syndrome, post-anginal sepsis or
      necrobacillosis, but in the context of this mini-review, all are included under
      the umbrella term of 'invasive F. necrophorum disease' (IFND). Although IFND has
      been well documented for over a century, it is quite a rare condition and modern
      day clinicians of various medical disciplines are frequently unaware of this
      organism and the severity of symptoms that it can cause. IFND classically occurs
      in previously healthy young people although the factors that trigger the invasive
      process are not fully understood. There are countless descriptive case histories
      and small series of cases of IFND disease in the literature and although commonly
      referred to as a 'forgotten' disease, in truth, it is probably best described as
      a repeatedly 'discovered' disease, as it may not always be included in medical
      curricula, and neither is it mentioned in some major medical textbooks. There is
      some evidence that IFND may be on the increase, particularly in the UK. The
      potential reasons for this are considered in this review along with an historical
      overview, and updates on disease incidence, patient demography, pathogenesis and
      laboratory diagnosis.

PMID- 16962964
TI  - A DNA-centric look at protein-DNA complexes.
AB  - The availability of many DNA-protein structures makes their classification timely
      and important. In this issue of Structure, the method of Akinori Sarai and his
      collaborators (Prabakaran et al., 2006) utilizes aspects of the binding
      interactions and DNA properties to identify seven clusters of structures with a
      classification scheme that differs significantly from previous approaches.

PMID- 16962965
TI  - A new GNAT in bacterial signaling?
AB  - Acyl-amino acids were discovered in the search for novel therapeutic agents
      produced by uncultured microorganisms. In this issue of Structure, Van Wagoner
      and Clardy (2006) find that the N-acyl-amino acid synthase FeeM bound to acyl
      tyrosine is the latest member of the GCN5-related N-acyltransferase superfamily.

PMID- 16962966
TI  - PcrA helicase, a prototype ATP-driven molecular motor.
AB  - Despite extensive studies, the mechanisms underlying molecular motor function are
      still poorly understood. Key to the mechanisms is the coupling of ATP hydrolysis
      to conformational changes of the motor protein. To investigate this coupling, we
      have conducted combined quantum mechanical/molecular mechanical simulations of
      PcrA helicase, a strikingly simple motor that translocates unidirectionally along
      single-stranded DNA (ssDNA). Our results reveal a close similarity in catalytic
      site structure and reaction pathway to those of F1-ATPase, and these similarities
      include a proton relay mechanism important for efficient ATP hydrolysis and an
      "arginine finger" residue that is key to the coupling of the chemical reaction to
      protein conformational changes. By means of in silico mutation studies, we
      identified the residue Q254 as being crucial for the coupling of ssDNA
      translocation to the actual catalytic event. Based on the present result for PcrA
      helicase and previous findings for F1-ATPase, we propose a general mechanism of
      ATP-driven molecular motor function.

PMID- 16962967
TI  - Classification of protein-DNA complexes based on structural descriptors.
AB  - We attempt to classify protein-DNA complexes by using a set of 11 descriptors,
      mainly characterizing protein-DNA interactions, including the number of atomic
      contacts at major and minor grooves, conformational deviations from standard B-
      and A-DNA forms, widths of DNA grooves, GC content, specificity measures of
      direct and indirect readouts, and buried surface area at the complex interface.
      The cluster analyses were carried out for a unique set of 62 complexes including
      a variety of protein motifs, and 7 distinct clusters were revealed from the
      analyses. We found that some proteins with the same motif are classified into
      different clusters, whereas different proteins with distinct motifs are
      classified into the same cluster. These results suggest that the conventional
      motif-based classification of DNA binding proteins may not necessarily correspond
      to structural and functional properties of protein-DNA complexes, and that the
      present classification will help to identify common properties and rules that
      govern protein-DNA recognition.

PMID- 16962968
TI  - Amyloid formation may involve alpha- to beta sheet interconversion via peptide
      plane flipping.
AB  - The toxic component of amyloid is not the mature fiber but a soluble prefibrillar
      intermediate. It has been proposed, from molecular dynamics simulations, that the
      precursor is composed of alpha sheet, which converts into the beta sheet of
      mature amyloid via peptide plane flipping. alpha sheet, not seen in proteins,
      occurs as isolated stretches of polypeptide. We show that the alpha- to beta
      sheet transition can occur by the flipping of alternate peptide planes. The flip
      can be described as alphaRalphaL<-->betabeta. A search conducted within sets of
      closely related protein crystal structures revealed that these flips are common,
      occurring in 8.5% of protein families. The average "alphaL" conformation found is
      in an adjacent and less populated region of the Ramachandran plot, as expected if
      the flanking peptide planes, being hydrogen bonded, are restricted in their
      movements. This work provides evidence for flips allowing direct alpha- to beta
      sheet interconversion.

PMID- 16962969
TI  - Crystal structure of ethylbenzene dehydrogenase from Aromatoleum aromaticum.
AB  - Anaerobic degradation of hydrocarbons was discovered a decade ago, and
      ethylbenzene dehydrogenase was one of the first characterized enzymes involved.
      The structure of the soluble periplasmic 165 kDa enzyme was established at 1.88 A
      resolution. It is a heterotrimer. The alpha subunit contains the catalytic center
      with a molybdenum held by two molybdopterin-guanine dinucleotides, one with an
      open pyran ring, and an iron-sulfur cluster with a histidine ligand. During
      catalysis, electrons produced by substrate oxidation are transferred to a heme in
      the gamma subunit and then presumably to a separate cytochrome involved in
      nitrate respiration. The beta subunit contains four iron-sulfur clusters and is
      structurally related to ferredoxins. The gamma subunit is the first known protein
      with a methionine and a lysine as axial heme ligands. The catalytic product was
      modeled into the active center, showing the reaction geometry. A mechanism
      consistent with activity and inhibition data of ethylbenzene-related compounds is
      proposed.

PMID- 16962970
TI  - The crystal structure of the rare-cutting restriction enzyme SdaI reveals
      unexpected domain architecture.
AB  - Rare-cutting restriction enzymes are important tools in genome analysis. We
      report here the crystal structure of SdaI restriction endonuclease, which is
      specific for the 8 bp sequence CCTGCA/GG ("/" designates the cleavage site).
      Unlike orthodox Type IIP enzymes, which are single domain proteins, the SdaI
      monomer is composed of two structural domains. The N domain contains a classical
      winged helix-turn-helix (wHTH) DNA binding motif, while the C domain shows a
      typical restriction endonuclease fold. The active site of SdaI is located within
      the C domain and represents a variant of the canonical PD-(D/E)XK motif. SdaI
      determinants of sequence specificity are clustered on the recognition helix of
      the wHTH motif at the N domain. The modular architecture of SdaI, wherein one
      domain mediates DNA binding while the other domain is predicted to catalyze
      hydrolysis, distinguishes SdaI from previously characterized restriction enzymes
      interacting with symmetric recognition sequences.

PMID- 16962971
TI  - Correlation between protein stability cores and protein folding kinetics: a case
      study on Pseudomonas aeruginosa apo-azurin.
AB  - This paper reports a combined computational and experimental study of the
      correlation between protein stability cores and folding kinetics. An empirical
      potential function was developed, and it was used for analyzing interaction
      energies among secondary structure elements. Studies on a beta sandwich protein,
      Pseudomonas aeruginosa azurin, showed that the computationally identified
      substructure with the strongest interactions in the native state is identical to
      the "interlocked pair" of beta strands, an invariant motif found in most sandwich
      like proteins. Moreover, previous and new in vitro folding results revealed that
      the identified substructure harbors most residues that form native-like
      interactions in the folding transition state. These observations demonstrate that
      the potential function is effective in revealing the relative strength of
      interactions among various protein parts; they also strengthen the suggestion
      that the most stable regions in native proteins favor stable interactions early
      during folding.

PMID- 16962972
TI  - Mechanism of gating and ion conductivity of a possible tetrameric pore in
      aquaporin-1.
AB  - While substrate permeation through monomeric pores of aquaporins is well
      characterized, little is known about the possible tetrameric pore. AQP1 has been
      suggested to function as an ion channel upon cGMP activation, although this idea
      has been controversial. Taking a theoretical and experimental approach, we
      demonstrate that the current might arise through the tetrameric pore and propose
      a plausible mechanism for conduction and gating. In response to simulated ion
      permeation, immediate hydration of the putative central pore was facilitated by
      moderate conformational changes of pore-lining residues. cGMP is found to
      interact with an unusually arginine-rich, cytoplasmic loop (loop D) facilitating
      its outward motion, which is hypothesized to trigger the opening of a cytoplasmic
      gate. Physiological analyses of wild-type AQP1 and a designed mutant in which two
      arginines of the gating loop are replaced by alanine provide experimental support
      for identifying a key component of the proposed mechanism.

PMID- 16962973
TI  - FeeM, an N-acyl amino acid synthase from an uncultured soil microbe: structure,
      mechanism, and acyl carrier protein binding.
AB  - Attempts to access antibiotics by capturing biosynthetic genes and pathways
      directly from environmental DNA, which is overwhelmingly derived from uncultured
      bacteria, have revealed a large and previously unknown family of N-acyl amino
      acid synthases (NASs). The structure of the NAS FeeM reveals structural
      similarity to the GCN5-related N-acyl transferases and acylhomoserine lactone
      synthases. The overall structure has a central beta sheet with alpha helices on
      both sides. A bound product at a cleft in the beta sheet identifies the active
      site and the structural basis for catalysis, and sequence conservation in this
      region indicates a bias for recognition over speed. FeeM interacts with an acyl
      carrier protein (FeeL), and the structure, mutagenesis, and enzymatic
      measurements reveal that a small hydrophobic pocket in alpha helix 5 dominates
      binding of FeeM to FeeL. The structural and mechanistic analyses suggest that the
      products of FeeM could be bacterial signaling agents.

PMID- 16962974
TI  - The Ig doublet Z1Z2: a model system for the hybrid analysis of conformational
      dynamics in Ig tandems from titin.
AB  - Titin is a gigantic elastic filament that determines sarcomere ultrastructure and
      stretch response in vertebrate muscle. It folds into numerous Ig and FnIII
      domains connected in tandem. Data on interdomain arrangements and dynamics are
      essential for understanding the function of this filament. Here, we report a
      mechanistic analysis of the conformational dynamics of two Ig domains from the N
      terminus of titin, Z1Z2, by using X-ray crystallography, SAXS, NMR relaxation
      data, and residual dipolar couplings in combination. Z1Z2 preferentially adopts
      semiextended conformations in solution, with close-hinge arrangements
      representing low-probability states. Although interdomain contacts are not
      observed, the linker appears to acquire moderate rigidity via small, local
      hydrophobic interactions. Thus, Z1Z2 constitutes an adaptable modular system with
      restricted dynamics. We speculate that its preexistent conformation contributes
      to the selective recruitment of the binding partner telethonin onto the
      repetitive surface of the filament. The structural interconversion of four Z1Z2
      conformers is analyzed.

PMID- 16962975
TI  - The crystal structure of the Venezuelan equine encephalitis alphavirus nsP2
      protease.
AB  - Alphavirus replication and propagation is dependent on the protease activity of
      the viral nsP2 protein, which cleaves the nsP1234 polyprotein replication complex
      into functional components. Thus, nsP2 is an attractive target for drug discovery
      efforts to combat highly pathogenic alphaviruses. Unfortunately, antiviral
      development has been hampered by a lack of structural information for the nsP2
      protease. Here, we report the crystal structure of the nsP2 protease (nsP2pro)
      from Venezuelan equine encephalitis alphavirus determined at 2.45 A resolution.
      The protease structure consists of two distinct domains. The nsP2pro N-terminal
      domain contains the catalytic dyad cysteine and histidine residues organized in a
      protein fold that differs significantly from any known cysteine protease or
      protein folds. The nsP2pro C-terminal domain displays structural similarity to S
      adenosyl-L-methionine-dependent RNA methyltransferases and provides essential
      elements that contribute to substrate recognition and may also regulate the
      structure of the substrate binding cleft.

PMID- 16962976
TI  - Crystal structures of the thi-box riboswitch bound to thiamine pyrophosphate
      analogs reveal adaptive RNA-small molecule recognition.
AB  - Riboswitches are noncoding mRNA elements that bind small-molecule metabolites
      with high affinity and specificity, and they regulate the expression of
      associated genes. The thi-box riboswitch can exhibit a 1000-fold higher affinity
      for thiamine pyrophosphate over closely related noncognate compounds such as
      thiamine monophosphate. To understand the chemical basis of thi-box pyrophosphate
      specificity, we have determined crystal structures of an E. coli thi-box bound to
      thiamine pyrophosphate, thiamine monophosphate, and the structural analogs
      benfotiamine and pyrithiamine. When bound to monophosphorylated compounds, the
      RNA elements that recognize the thiamine and phosphate moieties of the ligand
      move closer together. This allows the riboswitch to recognize the monophosphate
      in a manner similar to how it recognizes the beta-phosphate of thiamine
      pyrophosphate. In the pyrithiamine complex, the pyrophosphate binding site is
      largely unstructured. These results show how the riboswitch can bind to various
      metabolites, and why the thi-box preferentially binds thiamine pyrophosphate.

PMID- 16962977
TI  - A highly strained nuclear conformation of the exportin Cse1p revealed by
      molecular dynamics simulations.
AB  - To investigate the stability of the open nuclear state of the exportin Cse1p and
      its closing mechanism at the atomic level, we have performed multiple molecular
      dynamics simulations. The simulations revealed a strikingly fast transition of
      Cse1p from the open conformation to the closed cytoplasmic form, consistent with
      the proposal that Cse1p represents a "spring-loaded molecule." The structure of
      the ring-shaped state obtained in the simulations is remarkably close to the
      crystal structure of the cytoplasmic state, though the open nuclear structure was
      used as the only input. The conformational change is initially driven by release
      of strain due to RanGTP/importin-alpha binding. Subsequently, a stable closed
      state is formed, driven by attraction of electrostatically complementary
      interfaces. These results are consistent with and extend previous proposals.
      Reverse-charge and neutral mutants remained in an open state. The simulations
      predict a detailed reaction pathway and resolve the role of suggested hinge
      regions.

PMID- 16962978
TI  - Identification and typing of Cameroonian isolates of P. malariae using monoclonal
      antibodies against P. brasilianum.
AB  - In the present study, monoclonal antibodies raised against Plasmodium brasilianum
      were used to demonstrate, for the first time, antigenic diversity in natural
      populations of Plasmodium malariae isolates and as diagnostic tool to detect low
      parasitaemia P. malariae infection. Seventeen McAbs reacting by indirect
      immunoflorescence antibody (IFA) assay with no other Plasmodium species than P.
      brasilianum, were shown to react with P. malariae and were used for typing 29 P.
      malariae isolates from hyperendemic areas in Yaounde and in three villages of
      South Cameroon with parasitaemia ranging from 0.01% to 1.8%. All 29 isolates were
      distinguished by their ability to react with certain antibodies and considered as
      representing different isolates of P. malariae. One of these McAbs (No. 14)
      recognized P. malariae isolates to both in Yaounde and from Mengang but not in
      Edou or in Nkol Mvae, which may recognize a specific epitope that is less common
      in strains found in these villages and provide evidence of regional variation
      within the P. malariae parasites. The McAbs Nos. 16 and 17 were used to determine
      their usefulness as diagnostic tools for 30 suspected blood samples that were
      collected from patients with fever and it became clear that they could detect sub
      microscopical infections of P. malariae. This study supports the concept of using
      of P. brasilianum as a substitute for P. malariae during immuno-diagnosis of
      malaria in endemic areas where PCR assay cannot be used for identification of the
      P. malariae parasites. In addition our results for the first time provide
      evidence of considerable antigenic diversity of clinical P. malariae isolates in
      Cameroon.

PMID- 16962979
TI  - Central role of interleukin-15 in human immunodeficiency virus (HIV)-infected
      patients with visceral leishmaniasis.
AB  - To evaluate clinical and immunological parameters, interleukin (IL)-15 production
      and outcome of patients with visceral leishmaniasis (VL), including HIV positive
      patients, we analyzed 48 cases of VL. Clinical manifestations and response to
      therapy were similar in VL/HIV- and VL/HIV+ patients. However, relapses were more
      frequent in patients with HIV infection. Low levels of IL-15 concentrations were
      found in HIV+ patients without VL. These levels were comparable to concentrations
      obtained in healthy donors. We found a relationship between response to therapy
      and IL-15 levels. We found increased levels of IL-15 in VL/HIV- and VL/HIV+
      patients with clinical and parasitological response to therapy. Our data
      demonstrate that VL in HIV-infected patients occurs in subjects with severe
      immunodeficiency and presents high rate of relapses. Low levels of IL-15 in
      illness patients and restored production in cured persons suggest that this
      cytokine could play a central role in immune responses during Leishmania/HIV co
      infection.

PMID- 16962980
TI  - Dr. Kashmiri Lal Mittal.

PMID- 16962981
TI  - The effect of the obstetrics and gynecology clerkship on students' interest in a
      career in obstetrics and gynecology.
AB  - OBJECTIVE: The goal of this study was to determine the influence of the third
      year obstetrics and gynecology (OB/GYN) clerkship on male and female medical
      students' interest in a career in OB/GYN. STUDY DESIGN: Third-year medical
      students were surveyed about anticipated career field before and at the
      completion of the OB/GYN clerkship. The percentage of students considering OB/GYN
      as a career was computed before and after the clerkship. A multiple regression
      analysis was performed to examine the influence of various demographic factors on
      interest in OB/GYN. A Chi-square test was performed to establish different
      effects on males and females. RESULTS: A total of 268 students (55%) completed
      both surveys. Eight percent (mostly females) considered an OB/GYN career pre
      clerkship and 15% post-clerkship. Interest in OB/GYN pre-clerkship was the
      strongest predictor of interest post-clerkship. CONCLUSION: The OB/GYN clerkship
      increases students' interest in a career in OB/GYN. Most males are not
      considering OB/GYN as a career choice before the start of the clerkship.

PMID- 16962982
TI  - Identifying decomposition products in extracts of cellular metabolites.
AB  - Most methods of analyzing intracellular metabolites require extraction of
      metabolites from the cells. A concern in these methods is underestimation of
      metabolite levels due to incomplete extraction. In comparing extraction methods,
      then, it would seem that the best method for extracting a particular metabolite
      is the one that gives the largest yield. In extracting Escherichia coli with
      different methanol:water mixtures, we observed that >or=50% water gave an
      increased yield of nucleosides and bases compared with <or=20% water, as
      determined by liquid chromatography-tandem mass spectrometry analysis of the
      resulting extracts. Spiking of the extracts with isotope-labeled nucleotides
      revealed, however, that the high yield of nucleosides and bases occurred due to
      decomposition of nucleotides in the water-rich condition, not due to good
      extraction. Spiking combined with isotope labeling provides a general approach to
      detecting decomposition products in extracts of cellular metabolites. For
      extraction of E. coli with methanol:water, cold temperature and a high methanol
      fraction minimize artifacts due to metabolite decomposition.

PMID- 16962983
TI  - Exploratory data analysis of DNA microarrays by multivariate curve resolution.
AB  - In this work, the application of a multivariate curve resolution procedure based
      on alternating least squares optimization (MCR-ALS) for the analysis of data from
      DNA microarrays is proposed. For this purpose, simulated and publicly available
      experimental data sets have been analyzed. Application of MCR-ALS, a method that
      operates without the use of any training set, has enabled the resolution of the
      relevant information about different cancer lines classification using a set of
      few components; each of these defined by a sample and a pure gene expression
      profile. From resolved sample profiles, a classification of samples according to
      their origin is proposed. From the resolved pure gene expression profiles, a set
      of over- or underexpressed genes that could be related to the development of
      cancer diseases has been selected. Advantages of the MCR-ALS procedure in
      relation to other previously proposed procedures such as principal component
      analysis are discussed.

PMID- 16962984
TI  - Disulfide isomerization and thiol-disulfide exchange of long neurotoxins from the
      venom of Ophiophagus hannah.
AB  - Selective reduction on the Cys28-Cys32 disulfide of Ophiophagus hannah
      neurotoxins, Oh-4 and Oh-5, revealed that isomerization of this disulfide linkage
      caused the two toxins to have distinct conformation and different retention time
      on a reversed-phase column. The Cys28-Cys32 disulfide of Oh-4 and Oh-5 was prone
      to form mixed disulfides with glutathione following pseudo-first-order kinetics.
      In addition to glutathionylated proteins, Oh-4 could be promoted to convert into
      Oh-5 by thiol compounds. Isomerization of Oh-5 into Oh-4 was not observed in the
      presence of thiol compounds. Dethiolation of glutathionylated proteins produced
      Oh-4 and Oh-5. Oxidation of the partially reduced toxin with reduced Cys28 and
      Cys32 was exclusively converted into Oh-5 regardless of the absence or presence
      of GSH/GSSG. Acrylamide quenching studies revealed difference in degree of
      exposure of the single Trp27 between Oh-4 and Oh-5. Synthesized peptides with
      substitution of Trp27 or Phe31 with Gly abolished entirely the formation of
      disulfide-linked dimeric product noted with the peptide of wild-type sequence.
      These results suggest that disulfide formation and isomerization of Cys28-Cys32
      could be regulated by thiolation, and that the bulky aromatic residues Trp27 and
      Phe31 facilitate favorably the occurrence of disulfide isomerization of Cys28
      Cys32.

PMID- 16962986
TI  - Characterization and kinetic analysis of enzyme-substrate recognition by three
      recombinant lactococcal PepVs.
AB  - The dipeptidases (PepVs) from three typical lactococcal strains, Lactococcus
      lactis subsp. lactis (L9), L. lactis subsp. cremoris (L6) and L. lactis subsp.
      hordniae (hT) were cloned and characterized. The metal-binding, catalytic, and
      substrate-binding sites are highly conserved among of them. A computer-generated
      three-dimensional model suggested that the amino acid differences between these
      PepVs were mostly located away from the active center. L9 PepV does not hydrolyze
      dipeptides bearing Pro or D-amino acid at the C-terminal amino acid. Unlike PepV
      from Lactobacillus delbrueckii, L9 PepV does not cleave beta-Asp-His, and has
      little ability to cleave dipeptides containing a beta-alanine. In addition, L9
      PepV has a much higher kcat for dipeptides with an N-terminal Ala but a
      significantly higher Km when the N-terminal amino acid is Gly. The substrate
      recognition profile of PepV is further discussed on the basis of the kinetic
      analysis and the structural model.

PMID- 16962985
TI  - Nrf2 regulates an adaptive response protecting against oxidative damage following
      diquat-mediated formation of superoxide anion.
AB  - Mouse embryonic fibroblasts derived from Nrf2-/- mice (N0) and Nrf2+/+ mice (WT)
      have been used to characterize both basal and diquat (DQ)-induced oxidative
      stress levels and to examine Nrf2 activation during exposure to DQ-generated
      superoxide anion. Microarray analysis revealed that N0 cells have similar
      constitutive mRNA expression of genes responsible for the direct metabolism of
      reactive oxygen species but decreased expression of genes responsible for the
      production of reducing equivalents, repair of oxidized proteins and defense
      against lipid peroxidation, compared to WT cells. Nonetheless, the basal levels
      of ROS flux and oxidative damage biomarkers in WT and N0 cells were not
      different. Diquat dibromide (DQ), a non-electrophilic redox cycling bipyridylium
      herbicide, was used to generate intracellular superoxide anion. Isolated
      mitochondria from both cell lines exposed to DQ produced equivalent amounts of
      ROS, indicating a similar cellular capacity to generate ROS. However, N0 cells
      exposed to DQ for 24-h exhibited markedly decreased cell viability and aconitase
      activity as well as increased lipid peroxidation and glutathione oxidation,
      relative to WT cells. 2',7'-Dichlorofluorescein fluorescence was not increased in
      WT and N0 cells after 30-min of DQ exposure. However, increased levels of ROS
      were detected in N0 cells but not WT cells after 13-h of DQ treatment.
      Additionally, total glutathione concentrations increased in WT, but not N0 cells
      following a 24-h exposure to DQ. DQ exposure resulted in activation of an
      antioxidant response element-luciferase reporter gene, as well as induction of
      Nrf2-regulated genes in WT, but not N0 cells. Thus the enhanced sensitivity of N0
      cells does not reflect basal differences in antioxidative capacity, but rather an
      impaired ability to mount an adaptive response to sustained oxidative stress.

PMID- 16962987
TI  - Avicins, natural anticancer saponins, permeabilize mitochondrial membranes.
AB  - Avicins are a class of natural saponins with selective pro-apoptotic activity in
      cancer cells. In this work, we studied the influence of avicins on metabolic
      state of rat liver mitochondria. Avicin-treated mitochondria underwent a
      significant decrease in oxygen consumption rate that was completely restored by
      addition of exogenous cytochrome c. On the other hand, avicins increased the
      rotenone-insensitive oxidation of external NADH in the presence of exogenous
      cytochrome c, long before high amplitude swelling of mitochondria was observed.
      The increase in external NADH oxidation was cyclosporin A-insensitive. Avicin G
      significantly accelerated hydroperoxide-induced oxidation of mitochondrial
      endogenous NAD(P)H, the drop of the inner membrane potential and the high
      amplitude swelling of mitochondria. The obtained data might explain selective
      induction of apoptosis in tumor cells by avicins. Based on other studies showing
      that tumor cells generate hydroperoxides with a very high rate, avicins could
      provide a new strategy of anticancer therapy by sensitizing cells with high
      levels of reactive oxygen species to apoptosis.

PMID- 16962988
TI  - Protein kinase Calpha can undergo membrane localization via an alternative
      phosphatidylinositol 4,5-bisphosphate-dependent pathway.
AB  - Protein kinase Calpha (PKCalpha) activation is known to be dependent on the
      metabolic product of phosphatidylinositol 4,5-bisphosphate (PIP2) by
      phospholipase C (PLC). Here we report that fibroblasts may have an additional
      PIP2-dependent mechanism for membrane localization of PKCalpha. We observed
      PKCalpha membrane localization in both wild type and PLCgamma1 -/- mouse
      embryonic fibroblasts. Treatment of cells with a specific PLC inhibitor U73122
      resulted in increased PIP2 levels and enhanced membrane localization of PKCalpha.
      PKCalpha levels in the membrane fraction decreased following incubation with
      PLCgamma, but increased following treatment with U73122 or addition of exogenous
      PIP2 in vitro. In addition, PKCalpha interacted with PIP2-conjugate bead and
      mixed micelles containing PIP2. Finally, we found that PIP2 is involved in
      syndecan-4-mediated membrane localization of PKCalpha. Taken together, these data
      suggest that PIP2 might contribute to directly regulating the membrane
      localization of PKCalpha.

PMID- 16962989
TI  - Structural transition of the inhibitory region of troponin I within the regulated
      cardiac thin filament.
AB  - Contraction and relaxation of cardiac muscle are regulated by the inhibitory and
      regulatory regions of troponin I (cTnI). Our previous FRET studies showed that
      the inhibitory region of cTnI in isolated troponin experiences a structural
      transition from a beta-turn/coil motif to an extended conformation upon Ca(2+)
      activation. During the relaxation process, the kinetics of the reversal of this
      conformation is coupled to the closing of the Ca(2+)-induced open conformation of
      the N-domain of troponin C (cTnC) and an interaction between cTnC and cTnI in
      their interface. We have since extended the structural kinetic study of the
      inhibitory region to fully regulated thin filament. Single-tryptophan and single
      cysteine mutant cTnI(L129W/S151C) was labeled with 1,5-IAEDANS at Cys151, and the
      tryptophan-AEDANS pair served as a donor-acceptor pair. Labeled cTnI mutant was
      used to prepare regulated thin filaments. Ca(2+)-induced conformational changes
      in the segment of Trp129-Cys151 of cTnI were monitored by FRET sensitized
      acceptor (AEDANS) emission in Ca(2+) titration and stopped-flow measurements.
      Control experiments suggested energy transfer from endogenous tryptophan residues
      of actin and myosin S1 to AEDANS attached to Cys151 of cTnI was very small and
      Ca(2+) independent. The present results show that the rate of Ca(2+)-induced
      structural transition and Ca(2+) sensitivity of the inhibitory region of cTnI
      were modified by (1) thin filament formation, (2) the presence of strongly bound
      S1, and (3) PKA phosphorylation of the N-terminus of cTnI. Ca(2+) sensitivity was
      not significantly changed by the presence of cTm and actin. However, the cTn-cTm
      interaction decreased the cooperativity and kinetics of the structural transition
      within cTnI, while actin filaments elicited opposite effects. The strongly bound
      S1 significantly increased the Ca(2+) sensitivity and slowed down the kinetics of
      structural transition. In contrast, PKA phosphorylation of cTnI decreased the
      Ca(2+) sensitivity and accelerated the structural transition rate of the
      inhibitory region of cTnI on thin filaments. These results support the idea of a
      feedback mechanism by strong cross-bridge interaction with actin and provide
      insights on the molecular basis for the fine tuning of cardiac function by beta
      adrenergic stimulation.

PMID- 16962990
TI  - Ganglioside GM2 modulates the erythrocyte Ca2+-ATPase through its binding to the
      calmodulin-binding domain and its 'receptor'.
AB  - We have previously demonstrated that gangliosides were able to modulate the
      plasma membrane Ca2+-ATPase (PMCA) from porcine brain synaptosomes and porcine
      erythrocytes [Y. Zhao, X. Fan, F. Yang, X. Zhang, Arch. Biochem. Biophys. 427
      (2004) 204-212 and J. Zhang, Y. Zhao, J. Duan, F. Yang, X. Zhang, Arch. Biochem.
      Biophys. 444 (2005) 1-6]. The results indicated that the PMCA from porcine
      erythrocytes responded to gangliosides was different from that from synaptosomes,
      suggesting that the effects of gangliosides on the PMCA are isoform specific.
      Most interestingly, GM2 activated the PMCA from porcine erythrocytes at lower
      concentrations, but inhibited it at higher concentrations. In the present study,
      we found that GD1b, GM1 and GM3 did not affect the calpain digested PMCA from
      porcine erythrocytes or the intact enzyme in the presence of calmodulin, while
      GM2 inhibited it. Moreover, a synthetic peptide of 17 amino acid residues
      corresponding to the 'receptor' of the calmodulin-binding domain of the enzyme
      interfered with the inhibition of the enzyme by GM2 in competition assays. Taken
      together, our results suggested that gangliosides GD1b, GM1, GM2 (lower
      concentrations) and GM3 stimulated the PMCA by the interaction with calmodulin
      binding domain, while the interaction of GM2 with the 'receptor' of the
      calmodulin-binding domain of the enzyme led to the inhibition of the enzyme.

PMID- 16962991
TI  - TRP1 interacting PDZ-domain protein GIPC forms oligomers and is localized to
      intracellular vesicles in human melanocytes.
AB  - PDZ proteins coordinate assembly of protein complexes that participate in diverse
      biological processes. GIPC is a multifunctional PDZ protein that interacts with
      several soluble and membrane proteins. Unlike most PDZ proteins, GIPC contains
      single PDZ domain and the mechanisms by which GIPC mediates its actions remain
      unclear. We investigated the possibility that in lieu of multiple PDZ domains,
      GIPC forms multimers. Here, we demonstrate that GIPC can bind to itself and that
      the PDZ domain is involved in GIPC-GIPC interaction. Gel filtration, sucrose
      gradient centrifugation and chemical cross-linking showed that whereas bulk of
      cytosolic GIPC was present as monomer, oligomers with an estimated molecular mass
      corresponding to GIPC homotrimer were readily detectable in the membrane
      fraction. Modeling of GIPC PDZ domain showed feasibility of trimerization.
      Immunogold electron microscopy showed that GIPC is present in clusters near
      vesicles. Our data suggest that oligomers of GIPC mediate its functions in
      melanocytes.

PMID- 16962992
TI  - Direct interaction between caldesmon and cortactin.
AB  - Actin polymerization and depolymerization plays a central role in controlling a
      wide spectrum of cellular processes. There are many actin-binding proteins in
      eukaryotic cells. Their roles in the remodeling of the actin architecture and
      whether they work cooperatively await further study. Caldesmon (CaD) is an actin
      binding protein present in nearly all mammalian cells. Cortactin is another actin
      binding protein found mainly in the cell cortex. There have been no reports
      suggesting that CaD and cortactin interact with each other or work as partners.
      Here, we present evidence that CaD binds cortactin directly by overlay, pull-down
      assays, ELISA, and by column chromatography. The interaction involves the N
      terminal region of cortactin and the C-terminal region of CaD, and appears to be
      enhanced by divalent metal ions. Cortactin competes with both full-length CaD and
      its C-terminal fragment for actin binding. Binding of cortactin partially
      alleviates the inhibitory effect of CaD on the actomyosin ATPase activity. Not
      only can binding be demonstrated in vitro, the two proteins also co-localize in
      activated cells at the cortex. Whether such interactions bear any functional
      significance awaits further investigation.

PMID- 16962993
TI  - Memoir on the decomposition of water and of the bodies that it holds in solution
      by means of galvanic electricity. 1805.

PMID- 16962994
TI  - When ambiguity hurts: social standards moderate self-appraisals in generalized
      social phobia.
AB  - Thirty-nine individuals with generalized social phobia (social anxiety disorder)
      and 39 nonclinical controls performed a public speech after receiving cues about
      social standards. Using a novel video manipulation paradigm, one third of
      participants received cues indicating that standards for performance were high,
      one third received cues that standards were low, and the remaining third were
      given no explicit information about expected standards (i.e., standards were
      ambiguous). Individuals with social phobia performed objectively worse than
      controls in all conditions, but rated their performance as being worse only in
      the high and ambiguous standards conditions. These results suggest that in social
      phobia, negative self-perception is context-dependent. Implications for the
      cognitive model and treatment are discussed.

PMID- 16962995
TI  - Pyrroloquinoline quinone (PQQ) prevents fibril formation of alpha-synuclein.
AB  - Pyrroloquinoline quinone (PQQ) is a noncovalently bound cofactor in the bacterial
      oxidative metabolism of alcohols. PQQ also exists in plants and animals. Due to
      its inherent chemical feature, namely its free-radical scavenging properties, PQQ
      has been drawing attention from both the nutritional and the pharmacological
      viewpoint. alpha-Synuclein, a causative factor of Parkinson's disease (PD), has
      the propensity to oligomerize and form fibrils, and this tendency may play a
      crucial role in its toxicity. We show that PQQ prevents the amyloid fibril
      formation and aggregation of alpha-synuclein in vitro in a PQQ-concentration
      dependent manner. Moreover, PQQ forms a conjugate with alpha-synuclein, and this
      PQQ-conjugated alpha-synuclein is also able to prevent alpha-synuclein amyloid
      fibril formation. This is the first study to demonstrate the characteristics of
      PQQ as an anti-amyloid fibril-forming reagent. Agents that prevent the formation
      of amyloid fibrils might allow a novel therapeutic approach to PD. Therefore,
      together with further pharmacological approaches, PQQ is a candidate for future
      anti-PD reagent compounds.

PMID- 16962996
TI  - Butyrylcholinesterase is present in the human epidermis and is regulated by H2O2:
      more evidence for oxidative stress in vitiligo.
AB  - The human epidermis holds the capacity for autocrine cholinergic signal
      transduction, but the presence of butyrylcholinesterase (BchE) has not been shown
      so far. Our results demonstrate that this compartment transcribes a functional
      BchE. Its activity is even higher compared to acetylcholinesterase (AchE).
      Moreover, we show that BchE is subject to regulation by H(2)O(2) in a
      concentration-dependent manner as it was recently described for AchE. Epidermal
      BchE protein expression and enzyme activities are severely affected by H(2)O(2)
      in vitiligo as previously demonstrated for AchE. Removal/reduction of H(2)O(2) by
      a pseudocatalase PC-KUS yields normal/increased protein expression and
      activities. H(2)O(2)-mediated oxidation of methionine residues in BchE was
      confirmed by FT-Raman spectroscopy. Computer simulation supported major
      alteration of the enzyme active site and its tetramerisation domain suggesting
      deactivation of the enzyme due to H(2)O(2)-mediated oxidation. Based on our
      results we conclude that H(2)O(2) is a major player in the regulation of the
      cholinergic signal via both AchE and BchE and this signal is severely affected in
      the epidermis of patients with active vitiligo.

PMID- 16962997
TI  - Cerulenin-mediated apoptosis is involved in adenine metabolic pathway.
AB  - Cerulenin, a fatty acid synthase (FAS) inhibitor, induces apoptosis of variety of
      tumor cells. To elucidate mode of action by cerulenin, we employed the proteomics
      approach using Schizosaccharomyces pombe. The differential protein expression
      profile of S. pombe revealed that cerulenin modulated the expressions of proteins
      involved in stresses and metabolism, including both ade10 and adk1 proteins. The
      nutrient supplementation assay demonstrated that cerulenin affected enzymatic
      steps transferring a phosphoribosyl group. This result suggests that cerulenin
      accumulates AMP and p-ribosyl-s-amino-imidazole carboxamide (AICAR) and reduces
      other necessary nucleotides, which induces feedback inhibition of enzymes and the
      transcriptional regulation of related genes in de novo and salvage adenine
      metabolic pathway. Furthermore, the deregulation of adenine nucleotide synthesis
      may interfere ribonucleotide reductase and cause defects in cell cycle
      progression and chromosome segregation. In conclusion, cerulenin induces
      apoptosis through deregulation of adenine nucleotide biosynthesis resulting in
      nuclear division defects in S. pombe.

PMID- 16962998
TI  - The central DNA flap of the human immunodeficiency virus type 1 is important for
      viral replication.
AB  - Reverse transcription of the human immunodeficiency virus type 1 is characterized
      by the formation of a DNA flap at the center of the viral cDNA in between the
      central polypurine tract (cPPT) and the central termination sequence (CTS). The
      importance of the DNA flap for HIV-1 replication has been questioned, whereas its
      importance for lentiviral vector performance is well accepted. To investigate
      this controversy, we re-evaluated the importance of the DNA flap for HIV-1
      replication. A flap negative HIV-1 virus showed a 10- to 100-fold replication
      defect in comparison with a WT strain. Further characterization of the DNA flap
      in the context of lentiviral vectors showed that mutations in the DNA-flap
      sequence did not affect the transduction efficiency. Finally, introduction of a
      second cPPT/CTS sequence resulted in the presence of two DNA flaps but no higher
      transduction efficiency.

PMID- 16962999
TI  - Protein kinase Cdelta participates in insulin-induced activation of PKB via PDK1.
AB  - PKCdelta has been shown to be activated by insulin and to interact with insulin
      receptor and IRS. PKB(Akt) plays an important role in glucose transport and
      glycogen synthesis. In this study, we investigated the possibility that PKCdelta
      may be involved in insulin-induced activation of PKB. Studies were conducted on
      primary cultures of rat skeletal muscle. PKB was activated by insulin stimulation
      within 5min and reached a peak by 15-30min. Insulin also increased the physical
      association between PKCdelta with PKB and with PDK1. The insulin-induced PKCdelta
      PKB association was PI3K dependent. PKB-PKCdelta association was accounted for by
      the involvement of PDK1. Overexpression of dominant negative PKCdelta abrogated
      insulin-induced association of PKCdelta with both PKB and PDK1. Blockade of
      PKCdelta also decreased insulin-induced Thr308 PKB phosphorylation and PKB
      translocation. Moreover, PKCdelta inhibition reduced insulin-induced GSK3
      phosphorylation. The results indicate that insulin-activated PKCdelta interacts
      with PDK1 to regulate PKB.

PMID- 16963000
TI  - Musical scale properties are automatically processed in the human auditory
      cortex.
AB  - While listening to music, we immediately detect 'wrong' tones that do not match
      our expectations based on the prior context. This study aimed to determine
      whether such expectations can occur preattentively, as indexed by event-related
      potentials (ERPs), and whether these are modulated by attentional processes. To
      this end, we recorded ERPs in nonmusicians while they were presented with
      unfamiliar melodies, containing either a pitch deviating from the equal-tempered
      chromatic scale (out-of-tune) or a pitch deviating from the diatonic scale (out
      of-key). ERPs were recorded in a passive experiment in which subjects were
      distracted from the sounds and in an active experiment in which they were judging
      how incongruous each melody was. In both the experiments, pitch incongruities
      elicited an early frontal negativity that was not modulated by attentional focus.
      This early negativity, closely corresponding to the mismatch negativity (MMN) of
      the ERPs, was mainly originated in the auditory cortex and occurred in response
      to both pitch violations but with larger amplitude for the more salient out-of
      tune pitch than the less salient out-of-key pitch. Attentional processes leading
      to the conscious access of musical scale information were indexed by the late
      parietal positivity (resembling the P600 of the ERPs) elicited in response to
      both incongruous pitches in the active experiment only. Our results indicate that
      the relational properties of the musical scale are quickly and automatically
      extracted by the auditory cortex even before the intervention of focused
      attention.

PMID- 16963001
TI  - Getting his act together: roles of glutamate, nitric oxide, and dopamine in the
      medial preoptic area.
AB  - Gonadal hormones have primarily slow, genomically mediated effects, but
      copulation requires rapid interactions with a partner. A major way in which
      hormones facilitate male sexual behavior is by increasing production of
      neurotransmitter receptors or of enzymes that regulate neurotransmitter synthesis
      or release. Dopamine is an important facilitative neurotransmitter, and the
      medial preoptic area (MPOA) is a critical integrative site for male sexual
      behavior. MPOA dopamine is released before and during mating and facilitates
      copulation, genital reflexes, and sexual motivation. Gonadal hormones regulate
      dopamine release in the MPOA of male rats in part by increasing nitric oxide
      synthase (NOS) in the MPOA; the resultant increase in production of nitric oxide
      (NO) increases both basal and female-stimulated dopamine release. Glutamate also
      increases dopamine release via increased production of NO. At least some of the
      glutamatergic inputs to the MPOA are from the medial amygdala (MeA) and bed
      nucleus of the stria terminalis (BNST), which mediate the female-stimulated
      increase in dopamine, which in turn enhances copulatory ability. Extracellular
      glutamate in the MPOA increases during copulation, especially during ejaculation,
      and increased glutamate facilitates copulation and genital reflexes. Previous
      sexual experience also facilitates copulation and confers resistance to
      impairment by various lesions, drugs, and stress. Experience enhances processing
      of sexual stimuli, and its effects require activation of glutamate NMDA receptors
      and NOS in the MPOA. Neuronal NOS is increased in the MPOA of experienced males.
      Therefore, glutamate, NO, and dopamine interact in the MPOA to facilitate mating
      and to enhance future sexual responsiveness.

PMID- 16963002
TI  - Role of androgens and glucocorticoids in the regulation of diazepam-binding
      inhibitor mRNA levels in male mouse hypothalamus.
AB  - In peripheral organs, gonadal and adrenal steroids regulate diazepam-binding
      inhibitor (DBI) mRNA expression. In order to further investigate the involvement
      of peripheral steroid hormones in the modulation of brain DBI mRNA expression, we
      studied by semiquantitative in situ hybridization the effect of adrenalectomy
      (ADX) and castration (CX) and short-term replacement therapy on DBI mRNA levels
      in the male mouse hypothalamus. Cells expressing DBI mRNA were mostly observed in
      the arcuate nucleus, the median eminence and the ependyma bordering the third
      ventricle. In the median eminence and the ependyma bordering the third
      ventricule, the DBI gene expression was decreased in ADX rats and a single
      injection of corticosterone to ADX rats induced a significant increase in DBI
      gene expression at 3 and 12 h time intervals without completely restoring the
      basal DBI mRNA expression observed in intact mice. In the arcuate nucleus, ADX
      and corticosterone administration did not modify DBI mRNA expression. CX down
      regulated DBI gene expression in the ependyma bordering the third ventricle. The
      administration of dihydrotestosterone (3-24 h) completely reversed the inhibitory
      effect of CX. In the median eminence and arcuate nucleus, neither CX or
      dihydrotestosterone administration modified DBI mRNA levels. These results
      suggest that the effects of glucocorticoids on the hypothalamo-pituitary
      adrenocortical axis and androgens on the hypothalamo-pituitary-gonadal axis are
      mediated by DBI.

PMID- 16963003
TI  - Maternal deprivation in the early versus late postnatal period differentially
      affects growth and stress-induced corticosterone responses in adolescent rats.
AB  - Periodic maternal deprivation (MD) in the early postnatal period leads to
      permanently altered responsibility of the hypothalamus-pituitary-adrenocortical
      (HPA) axis to various types of stress. However, no reports appear to have
      described the effect of periodic MD under different conditions on growth of the
      developing rat and responsibility of the HPA axis to immobilization stress in
      adolescent rats. Furthermore, although body weight changes are known to affect
      stress responsibility, their relationship under periodic MD is not clear. The
      present study therefore used 4 different types of periodic MD: for 12 h/day from
      postnatal day (P)1 to P6 (12E group); for 3 h/day from P1 to P6 (3E group); for
      12 h/day from P16 to P21 (12L group); and for 3 h/day from P16 to P21 (3L group).
      Mean body weights were less in the 3E and 12E groups than in the control group
      until at least 9 weeks old, although body weight gain in the 3L and 12L groups
      was only transiently affected. Stress-induced corticosterone levels in the 3E and
      12E groups did not return to basal levels until at least 330 min after the
      termination of stress, while temporal variations of stress-induced corticosterone
      levels did not differ significantly between the 3L, 12L and control groups.
      Periodic MD in the first postnatal week affected growth of developing rats and
      responsibility of the HPA axis to immobilization stress in adolescent rats, and
      the extent of this modification was larger with MD for 12 h/day than with MD for
      3 h/day. Conversely, periodic MD from P16 to P21 had little effect. Periodic MD
      in the postnatal period induces long-term effects on growth and stress
      responsibility of the HPA axis. Furthermore, a critical age of the pup at the
      time of MD exists as well as a critical length of MD for inducing these effects.

PMID- 16963004
TI  - An anti-major histocompatibility complex class I intrabody protects endothelial
      cells from an attack by immune mediators.
AB  - OBJECTIVE: In vitro endothelialization has significantly improved the overall
      outcome of artificial prostheses in cardiovascular bypass surgery. A drawback of
      this tissue-engineering method remains the limited availability of suitable
      autologous endothelial cells (EC), especially in aged patients. Allogeneic EC
      with high proliferative capacity represent a potentially valuable alternative to
      a patient-specific vascular transplant. However, such cells carry the risk of
      being rejected due to Major Histocompatibility Complex (MHC) mismatches. METHODS:
      We investigated the effects of a very potent, intracellularly expressed antibody
      directed against MHC class I molecules, referred to as alpha-rat MHC I single
      chain variable fragment (sFv) intrabody. The intrabody was stably expressed in
      rat aortic EC (RAEC) following lentiviral vector-mediated gene transfer. The
      functional consequence of the MHC I down-regulation was tested in an allogeneic
      setting in two different in vitro assays. RESULTS: Stable expression of the alpha
      rat MHC I sFv intrabody resulted in a highly efficient depletion of surface MHC
      I. Thereby those RAEC which displayed low MHC I levels over extended periods of
      time were protected against killing by allo-specific, cytotoxic T cells (CTL) and
      by allo-antibody/complement-mediated lysis. CONCLUSIONS: These results
      demonstrate that intrabody-mediated down-regulation of MHC I reduces the
      immunogenicity of RAEC which may provide a suitable alternative supply for the
      lining of vascular prostheses.

PMID- 16963005
TI  - Role of KATP channels in sepsis.
AB  - Sepsis is an infection-induced inflammatory syndrome responsible for
      approximately 10% of all deaths worldwide. While pathophysiological mechanisms
      remain to be fully unravelled, new insights and discoveries are yielding
      significant improvements in outcome, particularly in the high mortality
      conditions of shock and multi-organ failure. One potential target is the ATP
      sensitive potassium (K(ATP)) channel, an ion channel critical to the
      cardiovascular stress response. Excessive activation of the vascular channel is
      now recognised as a major cause of hypotension and vascular hyporesponsiveness to
      catecholamines in septic shock. Some researchers advocate therapeutic blockade of
      these channels; however, outside the vasculature, channel opening may actually
      represent a protective mechanism against cellular damage. In this review we
      critically examine the role of the K(ATP) channel in sepsis.

PMID- 16963006
TI  - Differential regulation of soluble and membrane CD40L proteins in T cells.
AB  - CD40 ligand is an important immunoregulatory protein expressed by T cells. This
      protein exists as two isoforms, a membrane glycoprotein and a truncated soluble
      form. Here we demonstrate that membrane and soluble CD40L (sCD40L) are
      differentially regulated depending upon the activation stimulus. In T cell
      receptor activated cells, both membrane and sCD40L proteins are expressed and
      CD28 costimulation further increases their expression. The dissection of TCR
      generated signals into calcium and PKC-dependent pathways demonstrates that
      calcium is sufficient to induce membrane CD40L yet insufficient for sCD40L. In
      contrast, sCD40L is preferentially induced by PKC. Moreover, sCD40L production is
      blocked by Zn(2+)-dependent metalloproteinase inhibitors while membrane CD40L is
      concurrently increased. This profile suggests the potential involvement of the
      ADAM-10 protease which was subsequently shown to cleave membrane CD40L to
      generate sCD40L. Given the role of sCD40L in numerous disease pathologies and its
      ability to activate proximal and distal immune responses, the regulated cleavage
      of CD40L may likely contribute to disease mechanisms.

PMID- 16963007
TI  - Does the signal for the activation of T cells originate from the antigen
      presenting cell or the effector T-helper?
AB  - The present view is that the antigen-presenting cell (APC) processes and presents
      simultaneously on its surface several different antigens that are displayed
      randomly (with respect to their being Self or Nonself) as peptide-MHC complexes.
      The naive T-cell interacting with its ligand on the APC is activated by "co
      stimulation," the first step on the pathway to effectors. This view ignores the
      requirement for associative recognition of antigen (ARA) in mediating both the
      Self-Nonself discrimination and the regulation of effector class. The
      introduction of ARA as a requirement for these two decision functions highlights
      a critical role for the effector T-helper (eTh) and necessitates rethinking the
      contribution of the APC.

PMID- 16963008
TI  - Identification of hepatitis C virus (HCV) 2a-derived epitope peptides having the
      capacity to induce cytotoxic T lymphocytes in human leukocyte antigen-A24+ and
      HCV2a-infected patients.
AB  - Since virus-specific cytotoxic T lymphocytes (CTLs) play a critical role in
      preventing the spread of hepatitis C virus (HCV), vaccine-based HCV-specific CTL
      induction could be a promising strategy to treat HCV-infected patients. In this
      study, we tried to identify HCV2a-derived epitopes, which can induce human
      leukocyte antigen (HLA)-A24-restricted and peptide-specific CTLs. Peripheral
      blood mononuclear cells of HCV2a-infected patients or healthy donors were
      stimulated in vitro with HCV2a-derived peptides, which were prepared based on the
      HLA-A24 binding motif. As a result, three peptides (HCV2a 576-584, HCV2a 627-635,
      and HCV2a 1085-1094) efficiently induced peptide-specific CTLs from HLA-A24(+)
      HCV2a-infected patients as well as healthy donors. The cytotoxicity was exhibited
      by peptide-specific CD8(+) T cells in an HLA-A24-restricted manner. In addition,
      the HCV2a 627-635 peptide was frequently recognized by immunoglobulin G of HCV2a
      infected patients. These results indicate that the identified three HCV2a
      peptides might be applicable to peptide-based immunotherapy for HLA-A24(+) HCV2a
      infected patients.

PMID- 16963009
TI  - Effect of gliclazide on DNA damage in human peripheral blood lymphocytes and
      insulinoma mouse cells.
AB  - Type 2 diabetes mellitus is associated with increased oxidative stress. Free
      radicals produced during this stress may damage various cellular components.
      Gliclazide, a second-generation sulfonylurea, is an oral hypoglycemic drug that
      possesses antioxidant properties. Therefore, gliclazide may diminish the harmful
      consequences of oxidative stress in diabetic patients. The aim of our study was
      to evaluate the action of gliclazide on DNA damage and repair in normal human
      peripheral blood lymphocytes and insulinoma mouse cells (beta-TC-6). DNA damage
      and repair were induced by hydrogen peroxide, gamma and ultraviolet radiation and
      MNNG (N-methyl-N'-nitro-N-nitrosoguanidine) in the presence or absence of
      gliclazide and were analysed by the alkaline comet assay. DNA double-strand
      breaks were assayed by pulsed-field gel electrophoresis. Gliclazide protected DNA
      of both kinds of cells from DNA damage induced by chemicals and radiations. These
      results suggest that gliclazide may diminish the risk of free radical-related
      diseases associated with type 2 diabetes mellitus and possibly cancer.

PMID- 16963010
TI  - Follow-up studies on glycosylated flavonoids and their complexes with vanadium:
      their anti-hyperglycemic potential role in diabetes.
AB  - The present study sought to evaluate the hypoglycemic activities of free
      glycosylated flavonoids and flavonoid complexes with vanadium(IV), (VO(IV)), on
      glycemia in experimental diabetic rats. Besides free kaempferol-3,7-O-(alpha)
      dirhamnoside and kaempferol-3-neohesperidoside, complexes of these flavonoids
      with VO(IV) were administered by different routes in order to compare the potency
      of the compounds as well as the efficacy of insulin or VO(IV) in lowering serum
      glucose. Wistar rats were made diabetic by alloxan. The glycemia was assessed at
      different times after the administering of compounds. The equilibrium constants
      were determined by potentiometric study and two species with VO(IV) are proposed
      at physiological pH, VOH(2)L(2) for kaempferitrin and VOHL for kaempferol-3
      neohesperidoside. The latter exhibited hypoglycemic activity at all times
      examined with 50 and 100 mg/kg and the former reduced the glycemia from 0 to 6h
      by i.p. route. The administering of the complexes or 0.0146 mmol/kg VO(IV)
      resulted in a serum glucose-lowering effect over time in the case of i.p.
      treatment. A marked hypoglycemic effect was observed for 0.5IU of insulin
      (67.5%); 0.0146 mmol VO(IV) (16.8%); 0.0294 mmol kaempferitrin-VO(IV) (17.8%) and
      0.0286 mmol kaempferol-3-neohesperidoside-VO(IV) (56.0%) at 3h after i.p.
      treatment when compared with respective zero time in diabetic groups. Kaempferol
      3-neohesperidoside-VO(IV) was 2.5 times more effective than VO(IV), twice as
      effective as the free compound and three times more effective than kaempferitrin
      VO(IV). This is of particular interest since kaempferol-3-neohesperidoside
      appears to represent a suitable ligand for VO(IV) to mimic the efficacy of
      insulin in lowering serum glucose levels.

PMID- 16963011
TI  - DNA-based diagnosis of methylmalonic aciduria and homocystinuria, cblC type in a
      Chinese patient presenting with mild developmental delay.

PMID- 16963012
TI  - Development of 2 alternative enzyme-linked immunosorbent assays for routine
      screening of glutamic acid decarboxylase autoantibodies.
AB  - BACKGROUND: Antibodies to GAD65 (GADA) are considered highly predictive humoral
      markers of the type 1 diabetes mellitus and also of the insulin requirement in
      adult-onset patients presumptively classified as type 2 diabetics or LADA.
      METHODS: We present 2 methods for GADA assessment. The first one (fluid phase,
      ELISA Protocol A) is carried out in a 2-step procedure in which serum GADA are
      first allowed to react with a fixed dose of GAD65-biotin in solution and the
      residual free antigen is later assayed by a conventional ELISA. In the second
      test (solid phase, ELISA Protocol B) GADA are measured in an ELISA that depends
      on the ability of divalent autoantibodies to form a bridge between immobilized
      TrxGAD65 and liquid-phase biotinylated TrxGAD65. RESULTS: All normal control
      samples scored negative in both variants of ELISA and RBA, hence specificity was
      100% for all methods; the relative sensitivity of ELISA Protocol A respect of the
      RBA was 94% and that of ELISA Protocol B was 76%. CONCLUSIONS: Although ELISA
      Protocol A exhibited a better performance in terms of relative sensitivity than
      ELISA Protocol B, the simplicity of execution and the intended use of the assay
      must also be taken in consideration for the final choice.

PMID- 16963013
TI  - Interactions of serum hsCRP with apoB, apoB/AI ratio and some components of
      metabolic syndrome amplify the predictive values for coronary artery disease.
AB  - BACKGROUND: Plasma high-sensitivity CRP (hsCRP) is a marker of inflammation, and
      it is reported to link with coronary artery disease (CAD). Interactions between
      elevated serum hsCRP and other unfavorable risk factors have been proposed to
      cause high risk for CAD. OBJECTIVES: To examine the potential interactions
      between serum hsCRP and lipids and non-lipidic risk factors. METHODS: Markers of
      inflammation, the profiles of serum (apo)(lipo) proteins as well as classical
      risk factors were determined in 270 clinically stable angiographically documented
      subjects. The patients were stratified into tertiles according to hsCRP
      distribution. RESULTS: The Framingham CAD scores, relative and absolute risk for
      CAD and the prevalence of diabetes mellitus and hypertension were significantly
      higher in 3rd relative to 1st tertile of hsCRP. Subjects with hsCRP levels in the
      upper tertile had significant higher levels of serum glucose, triglyceride,
      apolipoprotein (apo)B, apoB/apoAI ratio and the counts of total leukocyte and
      neutrophil and lower levels of HDL-C, albumin and the ratio of albumin/globulins.
      Analyses by bivariate correlation as well as linear regression showed that serum
      hsCRP was associated positively with the occurrence of diabetes and hypertension,
      the counts of total leukocyte and neutrophil and the levels of serum glucose,
      uric acid, apoB, apoB/apoAI ratio, alpha1- and alpha2-globulins and inversely
      with albumin, albumin/globulin ratio and HDL-C. By constructing dummy combined
      variables, elevated hsCRP accompanied with male sex, diabetes, hypertension and
      high levels of serum glucose, apoB, apoB/apoAI ratio and cholesterol exhibited
      amplified high risk for CAD. CONCLUSIONS: The results show that hsCRP does
      interact multiplicatively with apoB and some variables of metabolic syndrome. The
      simultaneous assessment of hsCRP and interactive risk factors enhances
      discriminating value for CAD. It is suggested to use hsCRP in conjunction with
      apoB or apoB/apoAI ratio instead of cholesterol ratios in global risk assessment.

PMID- 16963014
TI  - Phonotactic constraints help to overcome effects of schwa deletion in French.
AB  - In a crossmodal priming experiment, visual targets (e.g. RENARD, 'fox') were
      auditorily primed by either an intact [see text] 'the fox' or reduced form [see
      text] 'the fox' of the word. When schwa deletion gave rise to an initial cluster
      that respected the phonotactic constraints of French (e.g. [lapluz] 'the lawn' in
      which /pl/ is a legal word beginning in French), there was a processing cost for
      the targets primed by the reduced form of the word compared to intact primes
      (e.g. [see text] 'the lawn'). However, when schwa deletion produced an initial
      cluster that violated the phonotactic constraints of French (e.g. [see text],
      where /Rn/ is not allowed as a word beginning), there was no penalty for targets
      primed by reduced compared to intact forms of the word. Assuming that listeners
      change their phonemic percept when confronted with phonotactically illegal
      sequences (Segui, Frauenfelder, & Halle, 2001), phonotactic constraints may help
      to restore the deleted schwa in sequences like le renard [see text] in French.

PMID- 16963015
TI  - Intelligent agents technology applied to tasks scheduling and communications
      management in a critical care telemonitoring system.
AB  - This work presents an important part of our telemedicine system for critical care
      units: a distributed module based on intelligent agents technology that is
      dedicated to the process management of a network for medical monitoring,
      including distribution and control of processing tasks and bandwidth management.
      The system provides the real-time acquisition and analysis of physiological data,
      the graphical visualisation of these data, and their transmission to a central
      system charged with the collection and control of all the information concerning
      the patient, including knowledge-based systems (KBS) for medical reasoning.

PMID- 16963016
TI  - Epithelial cell adhesion in the developing Drosophila retina is regulated by
      Atonal and the EGF receptor pathway.
AB  - In the Drosophila retina, photoreceptor differentiation is preceded by
      significant cell shape rearrangements within and immediately behind the
      morphogenetic furrow. Groups of cells become clustered into arcs and rosettes in
      the plane of the epithelium, from which the neurons subsequently emerge. These
      cell clusters also have differential adhesive properties: adherens junction
      components are upregulated relative to surrounding cells. Little is known about
      how these morphological changes are orchestrated and what their relevance is for
      subsequent neuronal differentiation. Here, we report that the transcription
      factor Atonal and the canonical EGF receptor signalling cascade are both required
      for this clustering and for the accompanying changes in cellular adhesion. In the
      absence of either component, no arcs are formed behind the furrow, and all cells
      show low Armadillo and DE-cadherin levels, although in the case of EGFR pathway
      mutants, single, presumptive R8 cells with high levels of adherens junction
      components can be seen. Atonal regulates DE-cadherin transcriptionally, whereas
      the EGFR pathway, acting through the transcription factor Pointed, exerts its
      effects on adherens junctions indirectly, at a post-transcriptional level. These
      observations define a new function for EGFR signalling in eye development and
      illustrate a mechanism for the control of epithelial morphology by developmental
      signals.

PMID- 16963017
TI  - R-spondin3 is required for mouse placental development.
AB  - Mouse R-spondin3 (Rspo3) is a member of the R-spondin protein family, which is
      characterized by furin-like cysteine-rich domains and a thrombospondin type 1
      repeat. Rspo3 has been proposed to function as a secretory molecule that promotes
      the Wnt/beta-catenin signaling pathway. We generated mice bearing a mutant Rspo3
      allele in which a lacZ-coding region replaced the coding region of the first
      exon. The homozygous mutant mice died at about embryonic day 10, due to impaired
      formation of the labyrinthine layer of the placenta. Rspo3 was expressed in the
      allantoic component of the labyrinth. In the homozygous mutant placentas, fetal
      blood vessels did not penetrate into the chorion, and expression of Gcm1,
      encoding the transcription factor glial cells missing-1 (Gcm1), was dramatically
      reduced in the chorionic trophoblast cells. These findings suggest a critical
      role for Rspo3 in the interaction between chorion and allantois in labyrinthine
      development.

PMID- 16963018
TI  - EGF signaling overcomes a uterine cell death associated with temporal mis
      coordination of organogenesis within the C. elegans egg-laying apparatus.
AB  - We isolated cog-3(ku212) as a C. elegans egg-laying defective mutant that is
      associated with a connection-of-gonad defective phenotype. cog-3(ku212) mutants
      appear to have no connection between the vulval and the uterine lumens at the
      appropriate stage because the uterine lumen develops with a temporal delay
      relative to the vulva and, thus, is not present when the connection normally
      forms. The lack of temporal synchronization between the vulva and the uterus is
      not due to precocious or accelerated vulval development. Instead, global
      gonadogenesis is mildly delayed relative to development of extra-gonadal tissue.
      cog-3(ku212) mutants also have a specific uterine fate defect. Normally, four
      cells of the uterine pi lineage respond via their LET-23 epidermal growth factor
      like receptors to a vulval-derived LIN-3 EGF signal and adopt the uterine vulval
      1 (uv1) fate. In cog-3(ku212) mutants, these four pi progeny cells are set aside
      as a pre-uv1 population but undergo necrosis prior to full differentiation. A
      gain-of-function mutation in LET-23 EGF receptor and ectopic expression of LIN-3
      EGF within the proper temporal constraints can rescue the uv1 defect, suggesting
      that a signaling defect, perhaps due to the temporal delay, is at fault. In
      support of this model, we demonstrate that lack of vulval-uterine coordination
      due to precocious vulval development also leads to uv1 cell differentiation
      defects.

PMID- 16963019
TI  - A review of total dissolved copper and its chemical speciation in San Francisco
      Bay, California.
AB  - Following basin-wide contamination from industrial emissions and urban
      development, total dissolved copper concentrations in some regions of San
      Francisco Bay have exceeded national and state guidelines for water quality. In
      the face of dramatic improvements in wastewater treatment and point source
      control, persisting elevated dissolved copper concentrations in the Bay have
      prompted multiple studies and extensive monitoring of this estuary since 1989.
      Statistical analyses of monitoring data show that total dissolved copper
      concentrations have declined in the North (by 17%) and South (29%) San Francisco
      Bay as well as in the Southern Sloughs (44%) from 1993 to 2001. Concentrations
      remain elevated in the farthest reaches of the Bay (Delta and Estuary Interface),
      and in the Central Bay. Dissolved copper concentrations throughout the Bay have
      also been positively correlated (r = 0.632, P < 0.0005, n = 598) with dissolved
      organic matter, supporting results from complimentary chemical speciation studies
      which indicate that high-affinity copper-binding organic ligands dominate the
      chemical speciation of dissolved copper in the Bay. These organic ligands
      typically bind > 99.9% of the dissolved copper, effectively buffering the system
      against small changes in dissolved copper concentrations, and maintaining free
      Cu(2+) concentrations well below the toxicity threshold of ambient aquatic
      microorganisms. In response to these findings, site-specific water quality
      criteria for dissolved copper concentrations are now being developed by the
      Regional Water Quality Board to provide a more appropriate standard for copper
      toxicity in the Bay-one based on its chemical speciation and bioavailability.

PMID- 16963020
TI  - Mediation of glutamatergic receptors and nitric oxide on striatal dopamine
      release evoked by anatoxin-a. An in vivo microdialysis study.
AB  - In this work, the involvement of ionotropic glutamatergic receptors and nitric
      oxide on striatal dopamine release induced by anatoxin-a was investigated in
      conscious and freely-moving rats. To study the participation of glutamatergic
      receptors, the effects of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic
      acid (AMPA)/kainate receptors antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione
      (CNQX), and N-methyl-D-aspartate (NMDA) receptor antagonists, dizocilpine (MK
      801) and d(-)-2-amino-5-phosphonopentanoic acid (APV), were examined. The
      perfusion of 3.5 mM anatoxin-a increased the extracellular dopamine levels to
      701% relative to the basal. When CNQX was administered with 3.5 mM anatoxin-a,
      the increase of dopamine levels was 29% smaller than that observed with anatoxin
      a alone. When MK-801 and APV were administered, the effect of anatoxin-a was
      attenuated 26% and 25% respectively in terms of that observed with anatoxin-a
      alone. And with CNQX plus MK-801, the effect of anatoxin-a was 53% inhibited in
      terms of the effect of anatoxin-a alone. These results suggest that the striatal
      dopamine release induced by anatoxin-a is partly mediated by activation of both
      ionotropic glutamatergic receptors. Since the neuronal form of nitric oxide
      synthase (nNOS) produces nitric oxide (NO) primarily in response to activation of
      NMDA receptors, it was tested if NO could play any role in the effect of anatoxin
      a. Treatment with NOS inhibitors, L-nitro-arginine methyl ester (L-NAME) and d(-)
      2-amino-5-phosphonopentanoic acid (7-NI), induced decreased anatoxin-a effects of
      22% and 26% respectively. In conclusion, the present in vivo results demonstrate
      that anatoxin-a induced an indirect activation of ionotropic glutamatergic
      receptors (NMDA and AMPA/kainite receptors), which stimulate striatal dopamine
      release. On the other hand, activation of NMDA receptors may elicit NO increased
      levels enhancing dopamine release.

PMID- 16963021
TI  - Isorhamnetin prevent endothelial cell injuries from oxidized LDL via activation
      of p38MAPK.
AB  - The present investigation was undertaken to determine the protective effects of
      isorhamnetin on endothelial cell line EA.hy926 injuries induced by oxidized low
      density lipoprotein (ox-LDL) and to uncover some of the underlying mechanisms of
      these effects. Indices such as cell viability, lactate dehydrogenase (LDH), and
      nitric oxide (NO) release were measured to evaluate the protective effects of
      isorhamnetin. 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity,
      superoxide dismutase (SOD), superoxide and reactive oxygen species (ROS)
      generation were also detected to evaluate the antioxidant effects of
      isorhamnetin. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was used
      to confirm the expression of endothelial nitric oxide synthase (eNOS) mRNA and
      lectin-like ox-LDL receptor-1 mRNA. Western blotting was used to evaluate the
      protein expression of this receptor and eNOS, as well as p38-mitogen-activated
      protein kinase (p38MAPK) phosphorylation and NF-kappaB p65 translocation. As a
      result, cell viability decreased significantly (P<0.01) after 24 h treatment with
      ox-LDL, accompanied with apparent secretion disorders such as NO reduction and
      LDH increase. Pretreatment with isorhamnetin resulted in remarkable increase of
      cell viability (P<0.05) and modulation of secretion disorders mediated by ox-LDL
      in a concentration-dependent manner. Besides, ox-LDL led to upregulation of
      lectin-like ox-LDL receptor-1, phosphorylation of p38MAPK, translocation of NF
      kappaB, and downregulation of the eNOS expression in endothelial cells.
      Isorhamnetin pretreatment inhibited the ox-LDL-induced downregulation of eNOS,
      upregulation of lectin-like ox-LDL receptor-1, phosphorylation of the p38MAPK and
      translocation of NF-kappaB. Moreover, isorhamnetin exhibited strong antioxidant
      activity, which was shown by its inhibition effects on ox-LDL-induced superoxide,
      ROS overproduction and significant SOD reduction. The data indicated the
      protective effects of isorhamnetin on endothelial cell line EA.hy926 from ox-LDL
      induced cell injuries. These effects were obtained via inhibition of lectin-like
      ox-LDL receptor-1 upregulation, interference of ox-LDL-mediated intracellular
      signaling pathway (p38MAPK activation, NF-kappaB nuclear translocation, eNOS
      expression) and the antioxidant activity of isorhamnetin.

PMID- 16963022
TI  - TGF-beta2 inhibits AKT activation and FGF-2-induced corneal endothelial cell
      proliferation.
AB  - The corneal endothelial cells form a boundary layer between anterior chamber and
      cornea. This single cell layer is important to maintain cornea transparency by
      eliciting net fluid transport into the anterior chamber. Injuries of the corneal
      endothelial layer in humans lead to corneal swelling and translucence. This
      hindrance is thought to be due to limited proliferative capacity of the
      endothelial layer. Fibroblast growth factor 2 (FGF-2) and transforming growth
      factor-beta 2 (TGF-beta2) are both found in aqueous humor, and these two
      cytokines promote and inhibit cell growth, respectively. The intracellular
      signaling mechanisms by which TGF-beta2 suppresses the mitogenic response to FGF
      2, however, remain unclear. We have addressed this question by investigating
      potential crosstalk between FGF-2-induced and TGF-beta2-regulated intracellular
      signaling events in cultured bovine corneal endothelial (BCE) cells. We found
      that TGF-beta2 and FGF-2 oppositely affect BCE cell proliferation and TGF-beta2
      can override the stimulating effects of FGF-2 by increasing COX-2 expression in
      these cells. Consistent with these findings, overexpression of COX-2
      significantly reduced FGF-2-induced cell proliferation whereas a COX-2 specific
      inhibitor NS398 reversed the effect of TGF-beta2 on FGF-2-induced cell
      proliferation. The COX-2 product prostaglandin E2 (PGE-2) blocks FGF-2-induced
      cell proliferation. Whereas FGF-2 stimulates cell proliferation by activating the
      AKT pathway, TGF-beta2 and PGE-2 both inhibit this pathway. In accordance with
      the effect of PGE-2, cAMP also inhibits FGF-2-induced AKT activation. These
      findings suggest that the mitogenic response to FGF-2 in vivo in the corneal
      endothelial layer may be inhibited by TGF-beta2-induced suppression of the PI3
      kinase/AKT signaling pathway.

PMID- 16963023
TI  - Cooperation of isoforms of laminin-332 and tenascin-CL during early adhesion and
      spreading of immortalized human corneal epithelial cells.
AB  - The repair of corneal wounds requires both epithelial cell adhesion and
      migration. We have studied the early adhesion process of immortalized human
      corneal epithelial (HCE) cells and show by field emission scanning electron
      microscopy (FESEM) that the cells first adhere via foot-like process to the
      growth substratum and later present lamellar spreading. During early adhesion
      indirect immunofluorescence showed that the cells codeposited laminin (Lm) -332
      and the large subunit of tenascin-C (Tn-CL) as a demarcated plaque beneath the
      cells. Instead, unprocessed Lm-332 (alpha 3'32) was found in a wider area in
      cells showing lamellar spreading and was also prominently expressed in the
      cytoplasm of the migrating marginal cells in the in vitro wounded HCE cultures.
      Confocal laser scanning microscopy (CLSM) showed that the Golgi apparatus was
      located to the vicinity of the Lm-332/Tn-CL-containing adhesion plaque and
      accordingly treatment of the cells with demecolcine, dispersing the Golgi
      apparatus, prevented the formation of plaques. This suggests that formation of
      the adhesion plaque depends on a direct vectorial secretion of Lm-332 and Tn-CL
      to the culture substratum. Instead, cytochalasin B treatment disrupted
      microfilaments and arborized the cells but did not affect the deposition of Tn
      CL/Lm-332 as a plaque beneath the cells. The suggestion was supported by
      immunoprecipitation experiments which showed that Tn-CL and Lm alpha 3' chain
      were found in cell-free matrices on the culture substratum of spreading cells but
      not at all (Tn-CL) or much less (Lm-332) in the culture medium. Quantitative cell
      adhesion experiments showed that HCE cells did not adhere to plain Tn-C coat and
      that integrin (Int) alpha(3)beta(1) mediated the adhesion of HCE cells to
      purified Lm-332 and to Lm-332/Tn-C while Int beta4 did not mediate adhesion to
      these proteins. Taken together, our data suggest that Lm-332 and Tn-CL cooperate
      in early adhesion process of HCE cells. Furthermore, the results show that Lm
      3'32 isoform functions in the spreading of the cells beyond the early adhesion
      stage and appears to emerge into HCE cells starting to migrate in experimental
      wounds.

PMID- 16963024
TI  - Photochemical and thermal reactivity of kynurenine.
AB  - The thermal and photochemical reactivity of kynurenine (KN), a tryptophan
      metabolite found in human lenses, has been studied in aqueous solution. The
      decarboxylation reaction of KN, resulting in the formation of 4-hydroxyquinoline,
      is reported for the first time. Rate constants for KN deamination and
      decarboxylation were determined in the temperature range 50-90 degrees C. The
      quantum yields for KN photodecomposition under argon were measured to be Phi
      Ar=(2.0+/-0.2) x 10(-5) and under oxygen Phi O2=(1.1+/-0.1) x 10(-4).

PMID- 16963025
TI  - Enzyme conformational dynamics during catalysis and in the 'resting state'
      monitored by hydrogen/deuterium exchange mass spectrometry.
AB  - This work reports the use of electrospray mass spectrometry for studying the
      conformational dynamics of enzymes by amide hydrogen/deuterium exchange (HDX)
      measurements. A rapid-mixing quench-flow approach allows comparisons to be made
      between the HDX kinetics of free enzymes with those under steady-state
      conditions. Experiments carried out on carboxypeptidase B in the absence of
      substrate and in the presence of saturating concentrations of hippuryl-Arg result
      in HDX kinetics that are indistinguishable. This finding implies that the
      conformational dynamics that mediate HDX are not significantly different in the
      resting state of the enzyme and during substrate turnover.

PMID- 16963026
TI  - Analysis of short RNAs in the malaria parasite and its red blood cell host.
AB  - RNA interference (RNAi) is an RNA degradation process that involves short, double
      stranded RNAs (dsRNA) as sequence specificity factors. The natural function of
      the RNAi machinery is to generate endogenous short double-stranded RNAs to
      regulate gene expression. It has been shown that treatment of Plasmodium
      falciparum, the etiologic agent of malaria, with dsRNA induces degradation of the
      corresponding microRNA (miRNA), yet typical RNAi-associated genes have not been
      identifiable in the parasite genome. To clarify this discrepancy we set out to
      clone short RNAs from P. falciparum-infected red blood cells and from purified
      parasites. We did not find any short RNA that was not a rRNA or tRNA fragment.
      Indeed, only known human miRNAs were isolated in parasite preparations indicating
      that very few if any short RNAs exist in P. falciparum. This suggests a different
      mechanism than classical RNAi in observations of dsRNA-mediated degradation. Of
      the human miRNAs identified, the human miRNA mir-451 accumulates at a very high
      level in both infected and healthy red blood cells. Interestingly, mir-451 was
      not detectable in a series of immortalised cell lines representing progenitor
      stages of all major blood lineages, suggesting that mir-451 may play a role in
      the differentiation of erythroid cells.

PMID- 16963027
TI  - Moderate overexpression of AIB1 triggers pre-neoplastic changes in mammary
      epithelium.
AB  - Here we report a new model of pre-clinical breast cancer which has been generated
      by overexpressing the steroid receptor coactivator AIB1 at moderate levels in
      breast epithelium. Transgenic female mice display mammary hyperplasia at the
      onset of puberty, consistent with enhanced proliferation of primary mammary
      epithelial cultures and augmented levels of cyclin D1 and E-cadherin. Studies of
      BrdU incorporation revealed that AIB1 localizes to the nucleus during or after S
      phase, implicating a new role for AIB1 in cell-cycle progression subsequent to
      G1. Our findings suggest that moderate overexpression of AIB1 may represent one
      of the pre-neoplastic changes in breast tissue.

PMID- 16963028
TI  - Diffusion of the mu opioid receptor at the surface of human neuroblastoma SH-SY5Y
      cells is restricted to permeable domains.
AB  - Previous single-molecule studies have shown a long-term diffusion superimposed to
      a short-term confinement of the human mu opioid (hMOP) receptors at the surface
      of heterologous cells. However, additional ensemble average measurements are
      required to reach a complete understanding of the undergoing process. Here, we
      analyse, by fluorescence recovery after photobleaching measurements, the lateral
      diffusion of fully functional T7-EGFP-hMOP receptors in neuroblastoma SH-SY5Y
      cells naturally expressing a low level of the wild-type receptor. Experiments
      carried out at variable observation radii demonstrate the restriction of the
      receptors diffusion to sub-micrometer sized domains. Furthermore, consistently
      with the long-term single-molecule data, the domains are found permeable.

PMID- 16963029
TI  - Interactions between PII proteins and the nitrogenase regulatory enzymes DraT and
      DraG in Azospirillum brasilense.
AB  - In Azospirillum brasilense ADP-ribosylation of dinitrogenase reductase (NifH)
      occurs in response to addition of ammonium to the extracellular medium and is
      mediated by dinitrogenase reductase ADP-ribosyltransferase (DraT) and reversed by
      dinitrogenase reductase glycohydrolase (DraG). The P(II) proteins GlnB and GlnZ
      have been implicated in regulation of DraT and DraG by an as yet unknown
      mechanism. Using pull-down experiments with His-tagged versions of DraT and DraG
      we have now shown that DraT binds to GlnB, but only to the deuridylylated form,
      and that DraG binds to both the uridylylated and deuridylylated forms of GlnZ.
      The demonstration of these specific protein complexes, together with our recent
      report of the ability of deuridylylated GlnZ to be sequestered to the cell
      membrane by the ammonia channel protein AmtB, offers new insights into the
      control of NifH ADP-ribosylation.

PMID- 16963030
TI  - Effects of dydrogesterone and of its stable metabolite, 20-alpha
      dihydrodydrogesterone, on nitric oxide synthesis in human endothelial cells.
AB  - OBJECTIVE: To investigate the effects of P, medroxyprogesterone acetate (MPA),
      and dydrogesterone (DYD) and its metabolite, 20-alpha-dihydrodydrogesterone (DHD)
      on endothelial synthesis of nitric oxide (NO) and characterize the signaling
      events recruited by these compounds. The Women's Health Initiative trial reports
      an excess of heart disease in postmenopausal women receiving MPA. DESIGN: Cell
      culture. SETTING: Research laboratory. PATIENT(S): Human endothelial cells from
      umbilical vein. INTERVENTION(S): Treatments with P, MPA, DYD, or DHD. MAIN
      OUTCOME MEASURE(S): Measure of NO release, endothelial nitric oxide synthase
      (eNOS) activity and expression, and activation of ERK 1/2 and Akt. RESULT(S): The
      administration of DYD alone or in combination with estrogen to endothelial cells
      results in neutral effects on NO synthesis and on the activity and expression of
      eNOS. In parallel, the stable metabolite DHD acts similarly to natural P,
      enhancing the expression of eNOS and inducing rapid activation of the enzyme
      through the regulation of the ERK 1/2 mitogen-activated protein kinase cascade.
      20-Alpha-dihydrodydrogesterone and P also potentiate eNOS induction by E2. On the
      contrary, MPA does not trigger eNOS enzymatic activation and decreases the extent
      of eNOS induction by E2. CONCLUSION(S): These findings support the concept that
      synthetic progestins act differently on vascular cells and that hormonal
      preparations may differ as to their cardiovascular effects.

PMID- 16963032
TI  - Mevastatin inhibits proliferation of rat ovarian theca-interstitial cells by
      blocking the mitogen-activated protein kinase pathway.
AB  - OBJECTIVE: To evaluate mechanisms involved in mevastatin-induced inhibition of
      proliferation of ovarian theca-interstitial cells. DESIGN: In vitro study.
      SETTING: Academic laboratory. ANIMAL(S): Immature Sprague-Dawley female rats.
      INTERVENTION(S): Ovarian theca-interstitial cells were cultured without and with
      mevastatin in the presence and absence of serum, mevalonic acid, and/or insulin.
      MAIN OUTCOME MEASURE(S): Proliferation was assessed by determination of DNA
      synthesis by thymidine incorporation assay. Activation of extracellular signal
      regulated kinase (Erk1/2) and of Akt/protein kinase B (PKB) was determined by
      ELISA. RESULT(S): Mevastatin induced a concentration-dependent inhibition of
      theca-interstitial cell proliferation in the absence and in the presence of
      serum. Inhibitory effects of mevastatin were partly abrogated by mevalonic acid
      and by insulin. Mevastatin blocked basal and insulin-induced phosphorylation of
      ERK1/2. In contrast, mevastatin had no significant effect on either basal or
      insulin-induced phosphorylation of Akt/PKB. CONCLUSION(S): Mevastatin inhibits
      proliferation of theca-interstitial cells by a mechanism that involves depletion
      of mevalonic acid and selective inhibition of basal and insulin-induced activity
      of Erk1/2 pathway, but not Akt/PKB pathway. These effects of mevastatin may be a
      result of decreased isoprenylation of small GTPases.

PMID- 16963033
TI  - Effects of L-norgestrel on the endothelium-dependent relaxation response of
      rabbit clitoral cavernous smooth muscles.
AB  - OBJECTIVE: To determine the effect of a popular oral contraceptive, L-norgestrel
      (a synthetic progestogen), on relaxing response of clitoral cavernous smooth
      muscles. DESIGN: Prospective, randomized study. SETTING: Academic facility.
      ANIMAL(S): Thirty adult female New Zealand White rabbits. INTERVENTION(S): We
      conducted isometric tension studies with norepinephrine, endothelium-dependent
      (acetylcholine) and endothelium-independent (sodium nitroprusside) vasodilators,
      and L-norgestrel. The effects of nonspecific nitric oxide synthase inhibitor
      (N(w)-nitro-L-arginine methyl ester) and the potassium channel blockers (1 and 10
      mM tetraethylammonium as well as 10 microM glibenclamide) on the reactivities of
      clitoral cavernous strips were investigated. MAIN OUTCOME MEASURE(S): Causation
      and power of developed tension after treatment. RESULT(S): Acetylcholine, sodium
      nitroprusside, and L-norgestrel produced concentration-dependent relaxation of
      the norepinephrine-precontracted strips. Both endothelium removal and treatment
      with 10 microM N(w)-nitro-L-arginine methyl ester completely inhibited the
      relaxation response to acetylcholine and L-norgestrel, and supplementation with
      10 mM L-arginine partially reversed the inhibition. Incubation with either
      tetraethylammonium (TEA) or glibenclamide reduced the L-norgestrel-induced
      relaxation in a dose-independent manner. CONCLUSION(S): The L-norgestrel-induced
      relaxation of the clitoral cavernous smooth muscle is endothelium and nitric
      oxide dependent and may be related to more than two types of potassium channels
      activation.

PMID- 16963034
TI  - The Pregnancy in Polycystic Ovary Syndrome study: baseline characteristics of the
      randomized cohort including racial effects.
AB  - OBJECTIVE: To report the baseline characteristics and racial differences in the
      polycystic ovary syndrome (PCOS) phenotype from a large multicenter clinical
      trial (PPCOS). DESIGN: Double-blind, randomized trial of three treatment regimens
      (with extended release metformin or clomiphene citrate). SETTING: Academic
      medical centers. PATIENT(S): Six hundred twenty-six infertile women with PCOS,
      aged 18-39 years, with elevated T levels and oligomenorrhea (exclusion of
      secondary causes), seeking pregnancy, with > or = 1 patent fallopian tube, normal
      uterine cavity, and a partner with sperm concentration > or = 20 x 10(6)/mL in >
      or = 1 ejaculate. INTERVENTION(S): Baseline characterization. MAIN OUTCOME
      MEASURE(S): Historical, biometric, and biochemical measures of PCOS. RESULT(S):
      There were no significant differences in baseline variables between treatment
      groups. The overall mean (+/-SD) age of the subjects was 28.1 +/- 4.0 years, and
      the mean body mass index was 35.2 kg/m2 (+/-8.7). Polycystic ovaries (PCOs) were
      present in 90.3% of the subjects, and the mean volume of each ovary was 10 cm3 or
      more. Of the subjects, 7% had ovaries that were discordant for PCO morphology. At
      baseline, 18.3% of the subjects had an abnormal fasting glucose level (> 100
      mg/dL). Asians tended to have a milder phenotype, and whites and African
      Americans were similar in these measures. CONCLUSION(S): The treatment groups
      were well matched for baseline parameters, and we have added further information
      to the PCOS phenotype.

PMID- 16963035
TI  - Long-term effects of tibolone on circulating levels of vascular cell adhesion
      molecules and E-selectin in postmenopausal women.
AB  - OBJECTIVE: Adherence of lymphocytes and monocytes to cell adhesion molecules
      (vascular cell adhesion molecules [VCAMs]) expressed by activated endothelial
      cells is the first step in the development of atherosclerotic disease. It is
      known that administration of tibolone for 8 weeks reduces serum levels of VCAMs
      in postmenopausal women. We evaluated the effects of the administration of
      tibolone in postmenopausal women for 1 year. DESIGN: Randomized, placebo
      controlled, crossover trial. SETTING: Healthy volunteers in an academic
      environment. PATIENT(S): Thirty-six healthy women in postmenopause since 1-4
      years. INTERVENTION(S): Group A received 2.5 mg/d of tibolone and group B
      received placebo for 12 months; treatment was subsequently crossed over for 1
      month. MAIN OUTCOME MEASURE(S): Serum concentrations of VCAM-1, intercellular
      adhesion molecule-1 (ICAM-1), and E-selectin were evaluated at baseline and at 6,
      12, and 13 months. RESULT(S): Baseline concentration of VCAM-1, ICAM-1, and E
      selectin were similar in both groups. At months 6 and 12, mean concentrations of
      VCAM-1, ICAM-1, and E-selectin decreased significantly in group A but not in
      group B. At month 13, levels returned to baseline in group A, whereas they
      decreased significantly in group B. CONCLUSION(S): Tibolone causes a rapid and
      sustained decrease in circulating levels of VCAMs; the effect is lost soon after
      stopping the treatment. Tibolone induces favorable changes in endothelial
      function and may exert a direct cardiovascular protective effect in
      postmenopausal women.

PMID- 16963036
TI  - Comparative effects of estradiol, raloxifene, and genistein on the uterus of
      ovariectomized mice.
AB  - To explore the uterine effects of administration of compounds that exert their
      bone-sparing functions through estrogen receptors, we administered 17beta-E2,
      raloxifene, or genistein to ovariectomized mice and analyzed the uterus weight
      and histology 4 weeks after beginning the treatments. Results indicated that
      raloxifene and genistein have partial agonistic properties on the uterus in
      estrogen-depleted mice, and that genistein induced apoptosis and several atypias
      in the glandular epithelium of endometrium, as demonstrated in hematoxylin-eosin
      stained histological sections.

PMID- 16963037
TI  - Association of a single dose of gonadotropin-releasing hormone antagonist with
      nitric oxide and embryo quality in in vitro fertilization cycles.
AB  - The patients undertaking a single-dose protocol for GnRH antagonist were
      associated with elevated serum and follicular levels of nitric oxide (NO) and
      decreased embryo quality scores compared with those who underwent the long
      protocol for GnRH agonist. The relatively poor embryo quality may be NO related
      instead of Fas related.

PMID- 16963038
TI  - Benefit of intracytoplasmic sperm injection in patients with a high incidence of
      triploidy in a prior in vitro fertilization cycle.
AB  - OBJECTIVE: To test the hypothesis that intracytoplasmic sperm injection (ICSI)
      overcomes a high incidence of tripronucleate zygotes resulting from standard
      insemination in a previous cycle. DESIGN: A retrospective analysis of matched
      pair cycles. SETTING: Assisted reproductive technologies (ART) program of Brigham
      and Women's Hospital. PATIENT(S): Ninety-five patients with a > or = 20%
      incidence of tripronucleate zygotes in an IVF cycle with use of ICSI in a
      subsequent attempt. INTERVENTION(S): Cycles with either standard insemination or
      ICSI. MAIN OUTCOME MEASURE(S): Incidence of diploid (2pn) and triploid (3pn)
      zygotes and number and quality of embryos obtained. RESULT(S): Patient age,
      ampules of gonadotropin used, peak E2, number of follicles at hCG trigger, and
      total number of oocytes were all significantly higher in the ICSI cycles, but the
      number of mature oocytes did not differ. After ICSI, the percentage of 2pn was
      higher (65.0% vs. 34.1%) and the percentage of 3pn was lower (5.0% vs. 33.9%)
      than after IVF, and more diploid embryos were obtained with ICSI (5.5 +/- 3.7 vs.
      3.4 +/- 2.2 [mean +/- SD]). There was no difference in embryo quality between the
      two groups. CONCLUSION(S): ICSI appears beneficial in women with a high 3pn
      occurrence from IVF because it increases the number of diploid zygotes without
      affecting embryo quality.

PMID- 16963039
TI  - Twin pregnancy outcome among cases of spontaneous conception, intrauterine
      insemination, and in vitro fertilization/intracytoplasmic sperm injection.
AB  - In a retrospective university hospital-based study of spontaneously conceived
      (SC), intrauterine insemination (IUI), and in vitro
      fertilization/intracytoplasmic sperm injection (IVF/ICSI) groups, this study
      finds maternal complications or the neonatal outcomes of twins to be similar
      between the groups.

PMID- 16963040
TI  - Ovarian stimulation with daily late follicular phase administration of low-dose
      human chorionic gonadotropin for in vitro fertilization: a prospective,
      randomized trial.
AB  - OBJECTIVE: Evaluate the effectiveness of a new ovarian stimulation (OS) protocol
      before IVF. DESIGN: Prospective clinical randomized trial. SETTING: Private
      centers. PATIENT(S): Three hundred and twenty-three intended-to-treat women
      candidates for IVF. INTERVENTION(S): Patients were divided into three groups and
      administered the following treatments: group A, recombinant hFSH from day 3 until
      follicles reached 13-14 mm, when recombinant hFSH was lowered to 75 IU daily and
      daily injections of 200 IU of hCG and a GnRH antagonist were administered until
      final maturation; group B, recombinant hFSH and a GnRH antagonist; group C,
      recombinant hFSH and a GnRH agonist. MAIN OUTCOME MEASURE(S): Primary outcome was
      the number of mature oocytes. Secondary outcomes included average initial and
      total recombinant hFSH dosage, serum E2 level on day of ovulation, number of
      oocytes retrieved, fertilization, number of top-quality embryos, endometrial
      thickness, implantation rate, pregnancy rate (PR), and incidence of ovarian
      hyperstimulation syndrome (OHSS). RESULT(S): The numbers of oocytes retrieved,
      mature oocytes, fertilization, top-quality embryos, and embryos transferred were
      comparable in all groups. Implantation rate, PR, and incidence of OHSS were also
      comparable. The total dose of recombinant hFSH was significantly lower in group A
      (1,674.7 +/- 59.4 IU, vs. 2,197.9 +/- 77.8 IU in group B and 2,156.7 +/- 80.9 IU
      in group C). CONCLUSION(S): This new OS protocol permits follicles and oocytes to
      fully develop, helps generate top-quality embryos, avoids premature ovulation,
      establishes clinical pregnancies, reduces administration of recombinant hFSH,
      minimizes costs, and does not increase the chances of OHSS.

PMID- 16963041
TI  - Plasma adrenomedullin levels in patients with polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate adrenomedullin levels in patients with polycystic ovary
      syndrome (PCOS). DESIGN: Prospective study. SETTING: Department of obstetrics and
      gynecology in a university hospital. PATIENT(S): Thirty-eight women with PCOS and
      29 healthy control subjects were enrolled in the study. INTERVENTION(S): Plasma
      adrenomedullin, serum androstenedione, free T, T, DHEAS, SHBG, thyrotropin, PRL,
      FSH, LH, and E2 were measured in each subject. Insulin resistance was estimated
      by fasting insulin level, fasting glucose:insulin ratio and 75-g glucose
      tolerance test for 2 hours. MAIN OUTCOME MEASURE(S): Plasma adrenomedullin levels
      and correlations among adrenomedullin and gonadotropins, female sex steroids,
      androgens, and insulin resistance. RESULT(S): There was no significant difference
      concerning plasma adrenomedullin concentrations between the groups. In patients
      with PCOS, fasting glucose, fasting insulin, body mass index, and free T were
      inversely correlated with the plasma adrenomedullin. Plasma adrenomedullin was
      significantly correlated with glucose:insulin ratio. After controlling for body
      mass index, there were no significant correlations between the above-mentioned
      parameters. CONCLUSION(S): Adrenomedullin may play a role in regulating the
      insulin metabolism in patients with PCOS.

PMID- 16963042
TI  - Current trends in the treatment of infertility in men with spinal cord injury.
AB  - OBJECTIVE: To determine current use of penile vibratory stimulation (PVS),
      electroejaculation (EEJ), and intrauterine insemination (IUI) in treatment of
      infertility in men with spinal cord injury (SCI). DESIGN: Prospective survey,
      retrospective chart review, and literature review. SETTING: Major university
      medical center. PATIENT(S): Male SCI patients and female partners.
      INTERVENTION(S): A survey administered to professionals determined current
      treatment methods for infertility in couples with SCI male partners. MAIN OUTCOME
      MEASURE(S): Sperm retrieval methods, ejaculation success rates, total motile
      sperm (TMS), IUI application, and IUI outcomes. RESULT(S): Twenty-eight percent
      of surveyed professionals do not retrieve sperm from ejaculates of SCI patients,
      relying instead on retrieval from reproductive tissues. Reasons for not offering
      PVS or EEJ were lack of familiarity, training, or equipment. Thirty-four percent
      do not offer IUI to these couples. Chart review showed that semen could be
      retrieved by PVS or EEJ in 95% of patients. Fifty-three percent and 43% of trials
      had TMS >5 and >10 x 10(6), respectively. Of survey respondents performing IUI,
      42% lacked enough data to estimate pregnancy rates (PRs) in these couples.
      Literature review showed IUI PRs between 9% and 18% per cycle and 30% and 60% per
      couple. CONCLUSION(S): Based on ejaculation success rates, TMS yields, and IUI
      outcomes, the methods of PVS, EEJ, and IUI warrant consideration in centers not
      currently offering these options for couples with SCI male partners.

PMID- 16963043
TI  - Citation classics in Fertility and sterility, 1975-2004.
AB  - The Science Citation Index of the Institute for Scientific Information was
      searched to identify the 102 most frequently cited articles in the Fertility and
      Sterility journal for the past 30 years. Identification of the citation classic
      articles provides resourceful perspectives on the evolution of Fertility and
      Sterility and reproductive medicine.

PMID- 16963044
TI  - Ongoing pregnancies after vitrification of human oocytes using a combined
      solution of ethylene glycol and dimethyl sulfoxide.
AB  - OBJECTIVE: To evaluate a vitrification solution using a mixture of two
      cryprotectant agents, dimethyl sulfoxide and ethylyne glycol plus sucrose, on the
      survival of human oocytes. DESIGN: Clinical study of cryopreservation of human
      metaphase II (MII) oocytes by vitrification. SETTING: University-affiliated IVF
      center. PATIENT(S): Infertile couples who agreed to have their surplus oocytes
      vitrified during the fresh IVF cycle. INTERVENTION(S): Vitrification of surplus
      oocytes subsequently used in the next cycle and assisted fertilization by
      intracytoplasmic sperm injection. MAIN OUTCOME MEASURE(S): Morphologic survival
      and normal fertilization, embryo development, and clinical outcome. RESULT(S): A
      total of 53 surplus MII oocytes from 6 patients were vitrified, of which 24 were
      thawed, resulting in 18 which survived morphologically (75%). Following
      insemination, 14 of the 18 surviving eggs were fertilized (77.7%). All zygotes
      developed into viable embryos that were replaced into each patient's uterus,
      resulting in two healthy pregnancies: one singleton and one twin. The pregnancies
      were ongoing. CONCLUSION(S): Cryopreservation of human MII oocytes by
      vitrification appears to be a promising procedure, though to assure optimal
      effectiveness of this protocol further studies should be undertaken.

PMID- 16963045
TI  - Correlation between first-trimester uterine artery Doppler indices and maternal
      serum free beta-human chorionic gonadotropin and pregnancy-associated plasma
      protein A.
AB  - OBJECTIVE: To assess the correlation between first-trimester uterine artery
      Doppler measurements and maternal serum levels of free beta-hCG and pregnancy
      associated plasma protein A (PAPP-A). DESIGN: Observational study. SETTING:
      Teaching hospital. PATIENT(S): Four hundred thirty-three women at 10-14 weeks of
      gestation. INTERVENTION(S): Doppler ultrasound of the uterine arteries.
      Fluorimetric immunoassays for free beta-hCG and PAPP-A. MAIN OUTCOME MEASURE(S):
      Uterine artery mean resistance index (RI), pulsatility index (PI), and number of
      early diastolic notches. Maternal serum levels of free beta-hCG and PAPP-A.
      RESULT(S): There were 401 uncomplicated pregnancies. In this group, free beta-hCG
      and PAPP-A did not significantly correlate with uterine artery RI or PI (r values
      between -0.089 and 0.029, all nonsignificant). Free beta-hCG and PAPP-A levels
      did not significantly change with the number of notches. Uterine artery
      resistance and PAPP-A levels were independently correlated with birth weight.
      CONCLUSION(S): Preliminary evidence suggests that first-trimester uterine artery
      Doppler measurements do not correlate with maternal serum levels of free beta-hCG
      and PAPP-A. This may allow their combined use in multivariate screening for
      pregnancy complications.

PMID- 16963046
TI  - Human testicular protein NYD-SP16 is involved in sperm capacitation and the
      acrosome reaction.
AB  - OBJECTIVE: To investigate the functional role of human testicular protein NYD
      SP16. DESIGN: Controlled experimental study. SETTING: University research
      laboratory. ANIMAL(S): ICR strain of mice. INTERVENTION(S): Testicular tissue and
      sperms were collected from 12- to 16-week-old male mice; cumulus-oocyte complexes
      were harvested from mature female mice after inducing superovulation. MAIN
      OUTCOME MEASURE(S): Expression of NYD-SP16 in mouse testis was analyzed by
      immunohistochemistry, its localization in mouse sperm was evaluated by
      immunofluorescence, and the functional role of NYD-SP16 in the process of
      fertilization was determined by CTC staining and in vitro fertilization.
      RESULT(S): In mouse testis, NYD-SP16 was immunolocalized to elongating spermatids
      and the staining was confined to the head. Immunoreactivity in mouse sperm was
      mainly seen in the acrosomal region and this expression pattern was not altered
      in capacitated sperm. However, after the acrosome reaction (AR), the intensity of
      the fluorescence staining attenuated significantly. NYD-SP16 antiserum
      significantly inhibited mouse sperm capacitation and the AR in a concentration
      dependent manner and the presence of anti-NYD-SP16 serum, during co-incubation of
      gametes, produced a concentration-dependent decrease in the percentage of
      zygotes. CONCLUSION(S): NYD-SP16 protein is a component of sperm acrosome, which
      plays a functional role in sperm capacitation and the AR and is consequently
      necessary for fertilization.

PMID- 16963047
TI  - Prostacyclin enhances mouse embryo development and hatching but not increased
      embryonic cell number and volume.
AB  - OBJECTIVE: To evaluate in vitro effects of prostacyclin (PGI2), we cultured mouse
      embryos with a PGI2 analogue, because human fallopian tube cells synthesize
      abundant amounts of PGI2. DESIGN: Animal model. SETTING: Animal study in a
      private infertility clinic. ANIMAL(S): Mouse embryos. INTERVENTION(S): In vitro
      effects of PGI2 analogue on mouse embryos. MAIN OUTCOME MEASURE(S): Development
      rate, blastocyst volume, rate of complete hatching, and cell number of hatched
      blastocysts. RESULT(S): Exposure to PGI2 analogue during the four-cell to morula
      stages was critical to enhanced embryo development and hatching but did not
      increase blastocyst volume or cell number of hatched blastocysts. The effects of
      PGI2 analogue were statistically significant at 1.0 micromol/L and 2.0 micromol/L
      in human tubal fluid medium, with or without 1% bovine serum albumin.
      CONCLUSION(S): Prostacyclin analogue enhanced embryo development and hatching,
      but PGI2 did not increase number of cells in hatched blastocysts or blastocyst
      volume.

PMID- 16963048
TI  - Pup birth from mouse oocytes in preantral follicles derived from vitrified and
      warmed ovaries followed by in vitro growth, in vitro maturation, and in vitro
      fertilization.
AB  - OBJECTIVE: To determine an optimum condition for vitrification of various animal
      species and to examine the developing capacity into pups of mouse oocytes in
      preantral follicles originating from cryopreserved ovaries. DESIGN: Experimental
      animal study. SETTING: Laboratory environment. ANIMAL(S): Normal (C57BL/6 x DBA2)
      F1 mice. INTERVENTION(S): Vitrification of animal ovaries using polyester sheets
      as a storage device; collection of oocyte-granulosa cell complexes by enzymatic
      treatment; and in vitro growth (IVG), in vitro maturation (IVM), and IVF, with
      embryo transplantation to pseudopregnant mice. MAIN OUTCOME MEASURE(S):
      Histological analysis of vitrified and warmed ovaries from several animal
      species; measurement of successful rates in IVG, IVM, and IVF of mouse oocytes in
      oocyte-granulosa cell complexes collected from the vitrified and warmed ovaries;
      and achievement of pup birth. RESULT(S): The vitrification method used was
      effective for storage of various animal ovaries. The oocytes enclosed in
      preantral follicles that were yielded from the vitrified-warmed ovaries preserved
      the capacity for developing into pups after IVG, IVM, and IVF. CONCLUSION(S): The
      findings indicated that ovarian cryopreservation by vitrification and subsequent
      IVG, IVM, and IVF are promising methods for restoring young cancer patients'
      fertility. The practical information presented here is applicable to human
      ovarian tissues.

PMID- 16963049
TI  - IGF-I is distinctly located in the bony fish pituitary as revealed for
      Oreochromis niloticus, the Nile tilapia, using real-time RT-PCR, in situ
      hybridisation and immunohistochemistry.
AB  - In bony fish, IGF-I released from the liver under the control of pituitary GH is
      the main endocrine regulator of growth, maintenance and development, and the
      amount of circulating IGF-I regulates synthesis and release of GH. In mammals and
      amphibia, evidence indicates that anterior pituitary endocrine cells also contain
      IGF-I. However, only preliminary and conflicting data exist on IGF-I gene
      expression in bony fish pituitary. Thus, we investigated the presence of IGF-I in
      the tilapia (Oreochromis niloticus) pituitary by quantitative real-time RT-PCR,
      in situ hybridisation and immunohistochemistry. The absolute amount of IGF-I mRNA
      in the whole pituitary (7.4+/-3.3 x 10(-3)pg/microg total RNA) was 1000-times
      lower than in liver (7.5+/-3.1 pg/microg total RNA). IGF-I peptide occurred in
      both neuro- and adenohypophysis but IGF-I gene expression was mainly restricted
      to the adenohypophysis. In the neurohypophysis, only few cells, probably
      pituicytes, contained IGF-I mRNA whereas IGF-I peptide was found also in numerous
      axons in the pars nervosa. In the adenohypophysis, both IGF-I mRNA and peptide
      were present in the majority of ACTH cells in all individuals investigated. In
      alpha-MSH cells, only IGF-I mRNA but no IGF-I peptide was detected likely
      suggesting an immediate release of IGF-I after synthesis. IGF-I mRNA and peptide
      were further observed in GH cells but their presence showed pronounced inter
      individual differences likely due to the physiological, e.g., nutritional, status
      of the individual. IGF-I released from the GH cells may serve as auto/paracrine
      mediator of a negative feedback mechanism in addition to liver-derived endocrine
      IGF-I. Generally, the constitutive synthesis of IGF-I in ACTH cells and the
      varying content in GH and alpha-MSH cells suggest particular roles for IGF-I.
      Local IGF-I may regulate synthesis and release of pituitary hormones in an
      autocrine and/or paracrine manner as well as prevent apoptosis and stimulate
      proliferation of endocrine cells.

PMID- 16963050
TI  - The distribution of squalene and non-cholesterol sterols in lipoproteins in type
      2 diabetes.
AB  - BACKGROUND: Lipoprotein distribution of non-cholesterol sterols was studied to
      evaluate in which lipoproteins they are carried in type 2 diabetes with body
      weight ranging from normal to overweight. METHODS: Serum and lipoprotein squalene
      and non-cholesterol sterols were quantitated with gas-liquid chromatography in 33
      diabetic subjects separated into normal (BMI < or = 25 kg/m2, n=10) and
      overweight (BMI > 25 kg/m2, n=23) groups. RESULTS: Two-thirds of the non
      cholesterol sterols were carried in LDL and one-fifth in HDL, whereas squalene
      was mainly in VLDL and LDL in both groups. In overweight versus normal weight
      subjects, the absorption marker concentrations and ratios to cholesterol in serum
      and lipoproteins were lower and those of synthesis higher. In both groups the
      synthesis and absorption markers were interrelated in all lipoproteins suggesting
      intact regulation of cholesterol metabolism. The absorption marker ratios to
      cholesterol were mostly carried in HDL (cholestanol) and IDL (campesterol and
      sitosterol), and synthesis markers in VLDL and IDL regardless of overweight.
      Synthesis marker ratios were underestimated in serum versus VLDL and IDL, and
      those of absorption markers in serum versus IDL and HDL (p<0.05 for all).
      Squalene was related to lathosterol in all lipoprotein fractions (e.g., in LDL
      r=+0.501, p<0.01) suggesting that in diabetes squalene, too, is an indicator of
      cholesterol synthesis. CONCLUSIONS: The absorption sterols are carried in IDL and
      HDL, and the synthesis markers in VLDL and IDL regardless of weight. The
      lipoprotein squalene and non-cholesterol sterol ratios were under- or
      overestimated in serum, and whether their evaluation in lipoproteins versus in
      serum only gives better information on cholesterol metabolism should be
      investigated further also in normal population.

PMID- 16963051
TI  - Activation of peripheral and in vivo transmigrated neutrophils in patients with
      stable coronary artery disease.
AB  - Accumulating evidence support a role of neutrophils in coronary artery disease
      (CAD). However little is known about the action of neutrophils at a local
      inflammatory site represented by an atherosclerotic plaque. To gain insight into
      these issues, we applied a skin blister model that permits analyses of in vivo
      transmigrated neutrophils. We hypothesised that the chronic inflammation in
      stable CAD mediates priming of neutrophils that impacts the out-come of
      neutrophil action at an inflammatory site. Thirteen patients with
      angiographically verified CAD were eligible for study entry together with 13 age
      and sex matched controls. Markers of inflammation (IL-6 and CRP), neutrophil
      activation (IL-8 and MMP-9/NGAL), and functional aspects (CD11b up-regulation and
      intracellular H(2)O(2) production) of peripheral and in vivo transmigrated
      neutrophils were studied. Systemic IL-8 and MMP-9/NGAL concentrations were
      significantly increased in patients indicating a primed state in circulating
      neutrophils. In vivo transmigrated neutrophils in stable CAD patients had an
      increased propensity to release MMP-9/NGAL and a reduced capacity to up-regulate
      CD11b and to produce hydrogen peroxide. These aberrations at the inflammatory
      site may be a consequence of a primed state of circulating neutrophils and point
      towards potential mechanisms whereby neutrophils at a local inflammatory site may
      contribute to the pathogenesis of CAD.

PMID- 16963052
TI  - Non-transferrin-bound iron is associated with plasma level of soluble
      intercellular adhesion molecule-1 but not with in vivo low-density lipoprotein
      oxidation.
AB  - BACKGROUND: Excess body iron is associated with increased cardiovascular disease
      risk, possibly via non-transferrin-bound iron (NTBI)-mediated enhancement of
      inflammation and oxidation of low-density lipoprotein (LDL). METHODS: We assessed
      this proposed atherosclerotic mechanism of body iron by determining the
      relationship of levels of serum iron parameters, including NTBI, with plasma
      markers of inflammation and LDL oxidation in 232 subjects who visited the
      outpatient clinic for hemochromatosis family screening. RESULTS: Plasma level of
      soluble intercellular adhesion molecule-1 (sICAM-1) was positively related to
      ferritin (standardized beta coefficient 0.16) and to NTBI (0.185) and negatively
      to total iron-binding capacity (TIBC, -0.166). Significant higher levels of sICAM
      1 were found for subjects in the highest quartile of NTBI compared to the lowest
      quartile of NTBI (122 microg/L (107-141) and 106 microg/L (89-125), median
      (interquartile range), p<0.001). Odds ratio of subjects having sICAM-1 level
      above 134 microg/L (75th percentile) in the highest and lowest quartile of NTBI
      amounted 2.3. White blood cell count was positively related to ferritin (0.149).
      High-sensitivity C-reactive protein, interleukin-6, interleukin-8, oxidized LDL,
      oxidized LDL/apolipoprotein B and IgG and IgM antibodies to oxidized LDL were not
      related to any of the markers of iron status. CONCLUSION: Excess body iron,
      reflected by elevated serum ferritin and NTBI and decreased TIBC, is associated
      with increased plasma level of sICAM-1 but not with markers of in vivo LDL
      oxidation.

PMID- 16963053
TI  - Angiotensin II increases expression and secretion of cathepsin F in cultured
      human monocyte-derived macrophages: an angiotensin II type 2 receptor-mediated
      effect.
AB  - Increasing evidence suggests that cathepsins and angiotensin II (AngII)
      participate in atherosclerosis, particularly in remodeling of the extracellular
      matrix of the inflamed arterial intima. Here, we show that AngII induces mRNA
      expression of cathepsin F, a member of the cysteine protease family, in human
      monocyte-derived macrophages. AngII did not affect the amount of intracellular
      cathepsin F protein, but significantly enhanced its secretion by the treated
      cells. The stimulatory effect of AngII was mediated by the AngII type 2 (AT(2))
      receptor, as demonstrated by the ability of the AT(2)-receptor antagonist
      PD123319 to block the AngII-induced increase in cathepsin F secretion. Our
      present data demonstrate a novel proatherogenic role for AngII, namely its
      ability to enhance secretion of lysosomal cathepsin F by monocyte-derived
      macrophages.

PMID- 16963054
TI  - A low level of C-reactive protein in Japanese adults and its association with
      cardiovascular risk factors: the Japan NCVC-Collaborative Inflammation Cohort
      (JNIC) study.
AB  - High-sensitivity C-reactive protein (hs-CRP) levels vary remarkably by race and
      ethnic group. We examined hs-CRP levels and their association with cardiovascular
      risk factors in the Japanese general population. The Japan National
      Cardiovascular Center (NCVC)-collaborative Inflammation Cohort (JNIC) Study
      recruited 5213 men and 7071 women aged > or = 40 years from seven communities in
      Japan during 2002-2004. hs-CRP was measured using nephelometry calibrated with
      CRM 470, the international plasma protein reference material. Traditional
      cardiovascular risk factors and their aggregation were studied in multivariate
      logistic models, stratified by overweight status. Median hs-CRP levels in men and
      women were 0.60 and 0.45 mg/L, respectively. The percentage of subjects with hs
      CRP levels < 1.0, 1.0-3.0, and > 3.0 mg/L was 67.4%, 22.0%, and 10.6% in men,
      respectively, and 76.3%, 16.7%, and 7.0% in women. hs-CRP levels showed
      significant linear associations with traditional risk factors. Overweight,
      hypertension, dyslipidemia (men only), smoking (men only), and diabetes (women
      only) contributed significantly to elevated hs-CRP levels. Overweight individuals
      with hypertension, dyslipidemia, and diabetes had a high prevalence of elevated
      hs-CRP levels in both sexes. Japanese adults have very low hs-CRP levels. An
      aggregation of metabolic risk factors is associated with elevated hs-CRP levels
      among overweight individuals, particularly in women.

PMID- 16963055
TI  - Suppression of hypercholesterolemic atherosclerosis by pentoxifylline and its
      mechanism.
AB  - Reactive oxygen species (ROS) have been implicated in the development of
      hypercholesterolemic atherosclerosis. Hypercholesterolemia increases the levels
      of platelet activating factor (PAF) and cytokines which are known to stimulate
      granulocytes and endothelial cells to produce ROS. Pentoxifylline (PTX) is an
      inhibitor of cytokines and PAF and would reduce the generation of ROS by
      granulocytes and endothelial cells. PTX therefore would be expected to reduce the
      development of hypercholesterolemic atherosclerosis. New Zealand white female
      rabbits were assigned to four groups: Group I (n=12), control; Group II (n=5),
      PTX control (40 mg/kg body weight daily orally); Group III (n=13), 0.5%
      cholesterol; Group IV (n=9), 0.5% cholesterol+PTX (40 mg/kg body weight daily
      orally). Blood samples were collected before (0 time) and after 1 and 2 months on
      experimental diets for measurement of serum triglycerides (TG), total cholesterol
      (TC), LDL-C, HDL-C and serum malondialdehyde (MDA), a lipid peroxidation product.
      At the end of 2 months the aorta was removed for measurement of atherosclerotic
      plaques, MDA, and aortic tissue chemiluminescence (Ao-CL), a marker for
      antioxidant reserve. Rabbits in Group III developed atherosclerosis (56.61+/
      6.90% of the intimal surface of aorta was covered with atherosclerotic plaques)
      which was associated with an increase in the serum TG, TC, LDL-C, HDL-C, TC/HDL
      C, MDA and aortic MDA and antioxidant reserve. PTX reduced the development of
      atherosclerosis by 38.1% and this was associated with decreases in serum MDA by
      32%, aortic MDA by 37%, and antioxidant reserve by 17.3% without changes in the
      serum lipids. These results suggest that ROS generated during
      hypercholesterolemia via cytokines and PAF may in part contribute to the
      development of hypercholesterolemic atherosclerosis and that suppression of
      production and activity of cytokines and PAF may reduce the development of
      hypercholesterolemic atherosclerosis.

PMID- 16963056
TI  - High-performance liquid chromatography determination of phenyllactic acid in MRS
      broth.
AB  - Phenyllactic acid (PLA) is an organic acid produced by some strains of lactic
      acid bacteria (LAB) and concentrations higher than 7.5 mg/ml inhibit growth of
      moulds and yeasts. Since PLA can be used to select LAB, a rapid, simple and cheap
      method for its determination is desirable. Typical methods for its analysis in
      broth are time-consuming, analytically complicated, and have poor recoveries.
      Herein we propose a simple and rapid method that does not require extraction, but
      only microfiltration of broth before injection in HPLC. The improved
      chromatographic conditions allow separation and quantification of PLA with a
      recovery of 98.7%. The method is highly reproducible with an intraday
      repeatability of the total peak area of 2.00%, while an interday repeatability of
      2.69%.

PMID- 16963057
TI  - Determination and characterization of phytochelatins by liquid chromatography
      coupled with on line chemical vapour generation and atomic fluorescence
      spectrometric detection.
AB  - Liquid chromatography (LC) coupled on line with UV/visible diode array detector
      (DAD) and cold vapour generation atomic fluorescence spectrometry (CVGAFS) has
      been developed for the speciation, determination and characterization of
      phytochelatins (PCs). The method is based on a bidimensional approach, e.g. on
      the analysis of synthetic PC solutions (apo-PCs and Cd(2+)-complexed PCs) (i) by
      size exclusion chromatography coupled to UV diode array detector (SEC-DAD); (ii)
      by the derivatization of PC -SH groups in SEC fractions by p
      hydroxymercurybenzoate (PHMB) and the indirect detection of PC-PHMB complexes by
      reversed phase liquid chromatography coupled to atomic fluorescence detector
      (RPLC-CVGAFS). MALDI-TOF/MS (matrix assisted laser desorption ionization time of
      flight mass spectrometry) analysis of underivatized synthetic PC samples was
      performed in order have a qualitative information of their composition.
      Quantitative analysis of synthetic PC solutions has been performed on the basis
      of peak area of PC-PHMB complexes of the mercury specific chromatogram and
      calibration curve of standard solution of glutathione (GSH) complexed to PHMB (GS
      PHMB). The limit of quantitation (LOQ) in terms of GS-PHMB complex was 90 nM (CV
      5%) with an injection volume of 35 microL, corresponding to 3.2 pmol (0.97 ng) of
      GSH. The method has been applied to analysis of extracts of cell cultures from
      Phaeodactylum tricornutum grown in Cd-containing nutrient solutions, analysed by
      SEC-DAD-CVGAFS and RPLC-DAD-CVGAFS.

PMID- 16963058
TI  - Programmed cross flow asymmetrical flow field-flow fractionation for the size
      separation of pullulans and hydroxypropyl cellulose.
AB  - Different functions for the programming of the cross flow in asymmetrical flow
      field-flow fractionation were studied with the aim to find the flow conditions
      most suitable for the molar mass distribution analysis of high molecular weight
      polysaccharides. A mixture of four differently sized pullulans covering the molar
      mass range 5.8 x 10(3)-1.6 x 10(6) g mol(-1) were used as a model sample. Two
      types of programs were studied, linear and exponential decays, both with and
      without initial periods of a constant cross flow. For comparison, nonprogrammed
      runs, i.e. using constant cross flow, were studied. It was found that
      exponentially decaying cross flow gave the most uniform molar mass selectivity
      across the fractogram. The programmed cross flow was applied to the molar mass
      distribution analysis of a technical quality of hydroxypropyl cellulose.

PMID- 16963059
TI  - Analysis of synthetic 19-norsteroids trenbolone, tetrahydrogestrinone and
      gestrinone by gas chromatography-mass spectrometry.
AB  - Tetrahydrogestrinone, gestrinone and trenbolone are synthetic 19-norsteroids with
      androgenic properties sharing a labile conjugated ketotrienyl motif. Their LC-MS
      analyses tend to overcome classical derivatization problems, a shortcoming to the
      use of GC-MS. Therefore, alternative derivatization procedures were evaluated.
      The procedure with methoxylamine: pyridine followed by TMSImid: MSTFA gave the
      best results. This is attributed to the stability of the MO-TMS derivatives
      hindering the formation of artifacts and tautomerism. A full method is presented
      including SPE, hydrolysis and liquid-liquid extraction. It was possible to
      confirm the analytes below 2 ng/mL in urine, being the method robust and cost
      effective also for screening proposes.

PMID- 16963060
TI  - Development of gas chromatography-mass spectrometry following microwave
      distillation and simultaneous headspace single-drop microextraction for fast
      determination of volatile fraction in Chinese herb.
AB  - In this work, for the first time, microwave distillation (MD) coupled with
      simultaneous headspace single-drop microextraction (HS-SDME) was developed for
      the determination of the volatile components in the Chinese herb, Artemisia
      capillaris Thunb. The volatile components were rapidly isolated by MD, and
      simultaneously extracted and concentrated by using a dodecane microdrop. The
      volatile oil extracted in the microdrop solvent was analyzed by gas
      chromatography-mass spectrometry (GC-MS). The experimental parameters of solvent
      selection, microdrop volume, microwave power, irradiation time and sample amount
      were investigated, and the method precision was also studied. The optimal
      parameters were extraction solvent of dodecane, solvent volume of 2.0 microL,
      microwave power of 400 W, irradiation time of 4 min, and sample amount of 2.0 g.
      Thirty-five volatile compounds present in Artemisia capillaris Thunb. were
      identified by using the proposed method, which were identical with those obtained
      by the conventional steam distillation method. The experimental results showed
      that MD-HS-SDME is a simple, rapid, reliable, and solvent-free technique for the
      determination of volatile compounds in Chinese herbs.

PMID- 16963061
TI  - Validation and evaluation of a high performance liquid chromatographic method for
      the determination of aluminium in wine.
AB  - A new method is reported for the determination of aluminium in wine by HPLC,
      involving derivatisation with 8-hydroxyquinoline (oxine) in the presence of
      micelles resulting in the formation of a fluorescent derivative. The complex is
      separated on a C18 column using a mobile phase of oxine - SDS - 35% acetonitrile,
      in a pH 7 buffer. The method was validated in the range 0.125-2 mg/l in a
      synthetic wine. The method was applied to the determination of aluminium in
      white, rose and red wines and results compared with those obtained by atomic
      absorption (GFAA). Aluminium concentrations found by HPLC in white wines were
      greater than those found in red wines. Further investigation using a polyphenol
      enriched white wine revealed a statistically significant inverse relationship
      between wine polyphenol content and the aluminium concentration determined by
      HPLC. The method may therefore be envisaged for the determination of unbound
      aluminium in wine.

PMID- 16963062
TI  - Rupture of thin films with resonant substrate patterning.
AB  - We study the stability and rupture of thin liquid films on patterned substrates.
      It is shown that striped patterning on a length scale comparable to that of the
      spinodal instability leads to a resonance effect and an imperfect bifurcation of
      equilibrium film shapes. Weakly nonlinear analysis gives predictions for film
      shapes, stability, growth rates, and rupture times, which are confirmed by
      numerical solution of the thin-film equation. Film behavior is qualitatively
      different in the resonant patterning regime, but with sufficiently large domains
      rupture occurs on a spinodal length scale regardless of patterning. Instabilities
      transverse to the patterning are examined and shown to behave similarly as
      disturbances to films on uniform substrates. We explain some previously reported
      effects in terms of the imperfect bifurcation.

PMID- 16963063
TI  - Electroosmosis in porous solids for high zeta potentials.
AB  - When surface potentials (or the surface charges) are high, the exponential term
      on the right-hand side of the Poisson-Boltzmann equation cannot be linearized.
      This nonlinear regime is systematically studied for various porous media and
      various physicochemical conditions. As in the linear regime, the numerical data
      for the electroosmotic coefficient when made dimensionless are shown to follow
      the semianalytical solution derived for a plane Poiseuille flow. Therefore, this
      coefficient can be deduced either from the specific surface or from the
      permeability and the formation factor.

PMID- 16963064
TI  - The effects of noise on computerized electrocardiogram measurements.
AB  - Computerized measurements provide objective and reproducible assessments of the
      electrocardiogram (ECG). These measurements may be affected by noise or other
      lead quality issues. The effects of noise on the repeatability of computer
      measured PR interval, QRS duration, QT interval, P/QRS/T axes, and ST levels were
      examined. METHODS: The 125 ECGs of the Common Standards for Quantitative
      Electrocardiography (CSE) measurement database (MO1 series) were merged with
      records from the MIT Noise Stress Test database. For each CSE ECG, 720 unique
      noise ECGs were created, for a total of 90,000 noisy ECGs. Computerized
      measurements from the noisy ECGs were compared to the original ECG measurements.
      The repeatability of the measurements was assessed as a function of a lead
      quality score. RESULTS: The repeatability of the measurements was found to be in
      excellent agreement with the original ECG measurements when the noise level was
      no worse than that of the original ECGs. Noise did not introduce any bias to the
      measurements, although not surprisingly, the variation of the errors increased as
      the lead quality degraded.

PMID- 16963065
TI  - Electrocardiogram on a chip: overview and first experiences of an
      electrocardiogram manufacturer of medium size.
AB  - The integration of an electrocardiogram (ECG) device into a chip is already well
      known in the field of implanted devices, such as pacemakers. For noninvasive
      electrocardiology, this approach has not been used on a broad scale commercially.
      The extension of electrocardiology to telemetry, home care, and special
      applications as in magnetic resonance imaging has spawned a new interest in
      highly miniaturized ECG devices. In our company, we are aiming for using highly
      integrated devices exactly in these fields. On one hand, the home monitoring
      market ("eHealth," "pHealth") requires small and lightweight devices ("ECG in an
      electrode"); on the other hand, the use of an ECG device within a hostile
      environment as in an magnetic resonance imaging machine with strong
      electromagnetic fields requires small dimensions of the device. Of these 2
      fields, the one of home monitoring is the most promising. There is a large
      population in need of such monitoring (eg, patients with congestive heart
      failure), and the cost issue in medical care drives the market in this direction.
      Projects in both fields will be presented as well as the first experiences as a
      middle-sized manufacturer in trying to produce an integrated ECG "device."

PMID- 16963066
TI  - Measuring mechanical function in the failing heart.
AB  - A common pathology in heart failure is a detrimental change in the mechanics of
      both contraction and filling. In familial hypertrophic cardiomyopathy, a genetic
      disease characterized by left ventricular hypertrophy and myofiber disarray, left
      ventricular diastolic dysfunction is common and contributes to congestive heart
      failure. In dilated cardiomyopathy, a common correlate to reduced wall thickening
      and increased chamber volume is an asynchronous activation of the left ventricle
      due to left bundle branch block. Local measures of the timing and magnitude of
      myocardial shortening and relaxation can be obtained with magnetic resonance (MR)
      tissue tagging, MR cine phase contrast, or MR cine displacement encoding. In
      familial hypertrophic cardiomyopathy, these methods have been shown to quantify
      the restrictive filling of the ventricle. Characterizing the regions of the
      failing heart which are activated late has allowed investigators to measure the
      change in protein expression in those regions compared to normal myocardium.
      Also, these MR imaging methods have led to a better quantification of the
      asynchronous activation in dilated cardiomyopathy, which can be used to predict
      response to resynchronization therapy with pacing.

PMID- 16963067
TI  - Thirty-year electrocardiographic follow-up after repair of tetralogy of Fallot or
      atrial septal defect.
AB  - BACKGROUND AND PURPOSE: Knowledge about long-term electrocardiographic changes
      after surgery for congenital heart disease is limited. METHODS: Eleven patients
      with corrected tetralogy of Fallot (ToF) and 14 with corrected atrial septal
      defect (ASD) were followed up at 20 and 30 years after surgery. RESULTS:
      Approximately 50% of the ASD group developed prolonged QRS duration. In the ToF
      group, 7 increased QRS duration by more than 20 milliseconds. Nearly all had
      right bundle-branch block, and 30% of them also had bifascicular block. Two in
      the ASD group developed first grade atrioventricular block. Five ASD and 6 ToF
      had prolonged corrected QT duration in the late postoperative phase. CONCLUSIONS:
      Even after primarily good results of surgery in congenital heart disease, unknown
      late effects may occur not only in complex lesions such as ToF but also after ASD
      correction. Regular medical checkups are important after surgical correction in
      congenital heart disease.

PMID- 16963068
TI  - Electrocardiographic findings in patients with cryptogenic ischemic stroke and
      patent foramen ovale.
AB  - BACKGROUND: A characteristic electrocardiogram (ECG) pattern called crochetage
      has been described in patients with atrial septal defects. Nevertheless, there
      are discrepancies regarding its frequency in patients with patent foramen ovale
      (PFO). OBJECTIVE: We analyzed the ECGs of patients who had cryptogenic stroke to
      study crochetage and other possible patterns in relation to PFO. METHODS: We
      prospectively included consecutive patients who have had a cryptogenic stroke and
      are undergoing a right-to-left shunt (RLS) study with transesophageal
      echocardiography and simultaneous transcranial Doppler. Two blinded and
      independent cardiologists analyzed the ECGs for crochetage, defined as a notch
      near the apex of the R wave in inferior limb leads, P wave abnormalities, and
      right bundle branch block (RBBB). RESULTS: We studied 104 patients whose mean age
      was 55.1 +/- 12.7 years; 60.6% were men. PFO was detected in 40.4% of patients.
      Cardiologists recorded crochetage in 26.2% of patients with PFO and 14.5% of
      patients without PFO (P = .204) and RBBB in 19% and 8% of patients, respectively
      (P = .132). P wave abnormalities were also detected in 54.8% of patients with PFO
      and 35.5% of patients without PFO (P = .070). In patients with PFO, biphasic P
      waves were more frequent in small RLS (P = .006). Although higher frequencies of
      crochetage in small RLS and RBBB in moderate RLS were detected, these differences
      did not reach statistical significance (P = .067 and P = .05, respectively).
      CONCLUSION: There is no characteristic ECG pattern to identify the patients with
      cryptogenic stroke.

PMID- 16963069
TI  - Correlation between results of head-up tilt test and clinical features in
      patients with syncope or presyncope.
AB  - BACKGROUND: Head-up tilt test (HUTT) is a well-established diagnostic tool in
      patients with suspected vasovagal syncope. Identification of factors that predict
      a positive HUTT result could simplify diagnostic steps. The aim of this study was
      to assess the correlation between clinical characteristics of patients with
      suspected neurocardiogenic syncope or presyncope and results of HUTT. MATERIALS
      AND METHODS: The study group consisted of 90 patients (55 men, 35 women; mean
      age, 43.2 +/- 17 years) with a history of syncope or presyncope. Cardiological
      and neurologic test findings were normal in every patient. The patients were
      tilted to a 70 degrees position for 45 minutes. If the first phase produced a
      negative response, the patients received 400 mug of sublingual nitroglycerin for
      the second phase and continued to be tilted for an additional 15 minutes.
      RESULTS: Sixty-four patients had a positive HUTT result, characterized by a
      vasodepressive response in 26 patients, mixed response in 24 patients, and
      cardioinhibitory response in 14 patients. In logistic regression analysis, the
      presence of prodromal symptoms was a predictor of a positive HUTT result (P =
      .002). CONCLUSION: We showed that the prognostic performance of clinical
      features, including the time interval between the last episode and HUTT, the
      number of syncope or presyncope episodes, age, and sex, was not ideal. The
      presence of prodromal symptoms might be more likely to predict a positive
      response during HUTT.

PMID- 16963070
TI  - Genotype-specific ECG patterns in long QT syndrome.
AB  - Different genetic types of the long QT syndrome (LQTS) are associated with
      distinct ECG manifestations, which relate to the type and magnitude of ion
      channel dysfunction. The QTc duration does not differentiate LQTS types, and
      therefore other static and dynamic ECG parameters reflecting changes in T wave
      morphology are used to describe phenotypic expression of different LQTS
      genotypes. LQT1 carriers usually have broad-based T waves, LQT2 carriers show low
      amplitude T waves with high incidence of notches, and LQT3 carriers frequently
      have extended ST segment with relatively narrow peaked T wave. This phenotypic
      differentiation could be enhanced by quantifying additional ECG parameters
      reflecting components of repolarization morphology as well as to evaluate
      dynamics of repolarization parameters. Heart rate dependency and dynamic behavior
      of repolarization parameters differ by genotype and further show that genotype
      indicates ECG phenotype in patients with LQTS. However, there is a substantial
      variation in repolarization abnormalities observed in the same subject and in the
      members of the same family indicating large differences in gene penetrance. In
      conclusion, comprehensive analyses of static and dynamic features of
      repolarization provide unique opportunity to understand electrophysiology of
      cardiac repolarization.

PMID- 16963071
TI  - Understanding proarrhythmic potential in therapeutic drug development: alternate
      strategies for measuring and tracking repolarization.

PMID- 16963072
TI  - Body-surface potential mapping to aid ablation of scar-related ventricular
      tachycardia.
AB  - We investigated whether body-surface potential mapping (BSPM) during catheter
      ablation of scar-related ventricular tachycardia (VT) could assist with the
      identification of VT exit sites. The study population consisted of 9 patients who
      underwent catheter ablation for VT, among whom 12 induced VTs with known exit
      sites were identified by entrainment criteria, pace mapping, or site of
      successful ablation. Paced activation was initiated at various intracardiac sites
      (20 +/- 4 sites per patient, a total of 180) documented by nonfluoroscopic
      electroanatomic mapping. During all episodes of VT and pacing, patients had a 120
      lead electrocardiogram recorded, and we analyzed these electrocardiographic data-
      by means of a similarity coefficient (SC) calculated over 100 milliseconds after
      the initiation of depolarization--to assess the similarity between the BSPM
      sequences occurring during VTs and those induced by pacing. Based on 245
      observations, the relationship between the SC and the distance of the pacing site
      from the VT exit site was then obtained for each individual VT by linear
      regression analysis: the distance D (in millimeters) from the VT exit site was
      related to SC by the regression equation D = slope (1 - SC2) + intercept. The
      parameters in this equation varied widely for the 12 VTs, but, in general, the
      nearer the pacing site was to the exit site, the better the goodness of match.
      This suggests that, although there is no universally applicable relationship
      between D and SC, BSPM could provide a useful adjunct to standard pace mapping,
      although additional processing--namely, an inverse calculation of epicardial
      potentials/isochrones--may be needed to reliably identify VT exit sites from body
      surface electrocardiograms.

PMID- 16963073
TI  - Location of Q-wave myocardial infarction in the era of cardiac magnetic resonance
      imaging techniques.

PMID- 16963074
TI  - Non-invasive flow cytometric monitoring of pHi in cell culture processes using
      EGFP.
AB  - We have described a new method for monitoring of cell culture processes using
      green fluorescent protein (GFP) fluorescent intensity. GFP has been used as a non
      invasive fluorescent reporter for various cellular processes. In this study,
      enhanced (EGFP) was found to be a very sensitive indicator of pHi in in vitro
      cell culture, and responded rapidly to extracellular pH (pHe) changes. EGFP
      transfected cells were evaluated for pHi changes by flow cytometry, by measuring
      EGFP fluorescent intensity, and compared to that of the pH-sensitive fluoroprobe,
      SNARF. EGFP intensity was found to reflect pHi values of cells at different pHe
      in the presence of nigericin and was affected by the addition of HCl and NaOH.
      Significant changes in pHi were detected at different stages of batch culture and
      when using different cell density and media composition. The EGFP assay can be
      used to minimise the perturbation of cells and processes under study, thus
      leading to accurate information about the physiological state of single cells in
      a population. The results establish the application of EGFP as a non-invasive
      indicator of pHi for monitoring of mammalian cell culture processes.

PMID- 16963075
TI  - Apyrene sperm from the triploid donors restore fecundity of cryopreserved semen
      in Bombyx mori.
AB  - Female moths of Bombyx mori were artificially inseminated with cryopreserved
      semen. The fertility of inseminated females varied from 0% to 76.9% depending on
      the strain. Addition of fresh semen from triploid males, which are infertile but
      whose semen includes intact apyrene sperm, greatly improved fecundity of
      cryopreserved semen from normal males. Frozen apyrene sperm from the triploid
      donors also improved the fecundity of females, inseminated with cryopreserved
      normal semen, but less than fresh semen from triploid males. Fertilization
      success in B. mori requires the presence of both, intact eupyrene and apyrene
      sperm. Our results show that eupyrene sperm tolerate the cryopreservation process
      better than apyrene sperm. Hence, we recommend to add apyrene sperm from the
      triploid donors as helper sperm routinely to cryopreserved semen in artificial
      insemination. This may advance the application of cryopreservation as a routine
      technique to maintain silkworm resources. The technique may also be applicable to
      other moth and butterfly species which, like B. mori, possess eupyrene and
      apyrene sperm.

PMID- 16963076
TI  - A new RXR agonist, HX630, suppresses intimal hyperplasia in a mouse blood flow
      cessation model.
AB  - The nuclear receptor retinoid X receptor (RXR) forms heterodimers with other
      nuclear receptors and exerts anti-inflammatory effects. RXR is implicated in the
      progression of arteriosclerosis; however, the effects of selective RXR activation
      on smooth muscle cell (SMC) proliferation are unknown. We synthesized a novel RXR
      agonist, HX630, and examined its effect on vascular SMC (VSMC) proliferation.
      Male C57BL/6 mice (n=15) were subjected to ligation of the left carotid artery
      and fed 5 or 10 mg/kg/day HX630 for 4 weeks. HX630-fed mice showed significantly
      suppressed intimal hyperplasia progression compared to that in control mice
      (0.286+/-0.093 vs. 1.022+/-0.134 intima/media ratio, P<0.05).
      Immunohistochemistry of the carotid artery showed that HX630 suppressed cytokine
      and adhesion molecule staining in lesions undergoing intimal thickening.
      Interleukin (IL)-1beta-induced VSMC proliferation was inhibited by HX630 and the
      expression of IL-6 mRNA and protein in VSMCs was suppressed. The RXR agonist
      HX630 exerts antiproliferative effects in VSMCs in vivo and in vitro. Thus, the
      RXR may serve as a therapeutic target for vascular injury and intimal thickening.

PMID- 16963077
TI  - Dietary fish oil reduces the occurrence of early afterdepolarizations in pig
      ventricular myocytes.
AB  - Fish oil reduces sudden cardiac death in post myocardial infarction patients.
      Life-threatening arrhythmias in heart failure are associated with repolarization
      abnormalities leading to EAD(1) formation. We examined the effects of
      incorporated fish oil omega3-PUFAs(2) on EAD formation in pig myocytes. Pigs were
      fed a diet rich in fish oil or sunflower oil (control) for 8 weeks. Myocytes were
      isolated by enzymatic dissociation and patch-clamped. Susceptibility to EAD
      formation was tested using E4031 (5 microM), a blocker of I(Kr). The fish oil
      diet in pigs resulted in increased incorporation of omega3-PUFAs in the
      sarcolemma of the myocytes compared to the control diet and caused a reduced
      occurrence of E4031-induced EADs in pig myocytes. A shorter action potential, a
      reduced action potential prolongation in response to E-4031 and a reduced
      reactivation of I(Ca,L) by omega3-PUFAs may explain the observed reduction in
      EADs. A diet rich in fish oil protects against EAD formation.

PMID- 16963078
TI  - Cardiomyocyte-restricted deletion of connexin43 during mouse development.
AB  - Although the gap junction protein Connexin43 (Cx43) is expressed in various cell
      types during embryonic development, mice with a global inactivation of Cx43
      survive until birth but die perinatally due to an obstruction of the right
      ventricular outflow tract of the heart. To analyze the functional role of Cx43
      gap junction channels in cardiomyocytes of the developing and early postnatal
      heart, we used alphaMyHC-Cre mice to ablate Cx43 expression selectively in
      cardiomyocytes during development. We found efficient ablation of Cx43 in
      cardiomyocytes during embryonic development starting at embryonic day (ED) 9.5 in
      the ventricular wall. Analyses of cardiac Cx43 protein at birth indicated
      complete loss of Cx43 expression in cardiomyocytes. All mice homozygously
      deficient for Cx43 in cardiomyocytes died until postnatal day (PD) 16.
      Heterozygous inactivation of Cx43 in cardiomyocytes neither altered atrial nor
      ventricular activation, but homozygous ablation led to changes in ventricular
      activation, i.e. significant decrease of the QRS-amplitude and prolonged QRS
      duration already at PD 4. Cardiac morphology was similar to controls until PD 1,
      but subtle morphological changes were found in a subgroup of mutant mice at later
      stages. Besides narrowing of the ventricular outlet region at PD 6, hypertrophy
      of ventricular myocardium was found at PD 12. Our data indicate that complete
      inactivation of cardiac Cx43 during development predisposes hearts to develop
      postnatal morphological alterations, which differ from outflow tract obstructions
      described for Cx43 null mice. In addition, complete loss of cardiac Cx43 protein
      during development correlates with slowed ventricular activation at PD 4, impairs
      viability during development, and leads to death of all mutant mice until PD 16.

PMID- 16963079
TI  - Structure of Leishmania mexicana phosphomannomutase highlights similarities with
      human isoforms.
AB  - Phosphomannomutase (PMM) catalyses the conversion of mannose-6-phosphate to
      mannose-1-phosphate, an essential step in mannose activation and the biosynthesis
      of glycoconjugates in all eukaryotes. Deletion of PMM from Leishmania mexicana
      results in loss of virulence, suggesting that PMM is a promising drug target for
      the development of anti-leishmanial inhibitors. We report the crystallization and
      structure determination to 2.1 A of L. mexicana PMM alone and in complex with
      glucose-1,6-bisphosphate to 2.9 A. PMM is a member of the haloacid dehalogenase
      (HAD) family, but has a novel dimeric structure and a distinct cap domain of
      unique topology. Although the structure is novel within the HAD family, the
      leishmanial enzyme shows a high degree of similarity with its human isoforms. We
      have generated L. major PMM knockouts, which are avirulent. We expressed the
      human pmm2 gene in the Leishmania PMM knockout, but despite the similarity
      between Leishmania and human PMM, expression of the human gene did not restore
      virulence. Similarities in the structure of the parasite enzyme and its human
      isoforms suggest that the development of parasite-selective inhibitors will not
      be an easy task.

PMID- 16963080
TI  - Engineering, biophysical characterisation and binding properties of a soluble
      mutant form of annexin A2 domain IV that adopts a partially folded conformation.
AB  - The four approximately 75-residue domains (repeats) that constitute the annexin
      core structure all possess an identical five-alpha-helix bundle topology, but the
      physico-chemical properties of the isolated domains are different. Domain IV of
      the annexins has previously been expressed only as inclusion bodies, resistant to
      solubilisation. Analysis of the conserved, exposed hydrophobic residues of the
      four annexin domains reveals that domain IV contains the largest number of
      hydrophobic residues involved in interfacial contacts with the other domains. We
      designed five constructs of domain IV of annexin A2 in which several interfacial
      hydrophobic residues were substituted by hydrophilic residues. The mutant domain,
      in which all fully exposed hydrophobic interfacial residues were substituted, was
      isolated as a soluble protein. Circular dichroism measurements indicate that it
      harbours a high content of alpha-helical secondary structure and some tertiary
      structure. The CD-monitored (lambda=222 nm) thermal melting profile suggests a
      weak cooperative transition. Nuclear magnetic resonance (1H-15N) correlation
      spectroscopy reveals heterogeneous line broadening and an intermediate spectral
      dispersion. These properties are indicative of a partially folded protein in
      which some residues are in a fairly structured conformation, whereas others are
      in an unfolded state. This conclusion is corroborated by 1-anilinonaphthalene-8
      sulfonate fluorescence (ANS) analyses. Surface plasmon resonance measurements
      also indicate that this domain binds heparin, a known ligand of domain IV in the
      full-length annexin A2, although with lower affinity.

PMID- 16963081
TI  - The paradoxical behavior of a highly structured misfolded intermediate in RNA
      folding.
AB  - Like many structured RNAs, the Tetrahymena group I ribozyme is prone to
      misfolding. Here we probe a long-lived misfolded species, referred to as M, and
      uncover paradoxical aspects of its structure and folding. Previous work indicated
      that a non-native local secondary structure, termed alt P3, led to formation of M
      during folding in vitro. Surprisingly, hydroxyl radical footprinting,
      fluorescence measurements with site-specifically incorporated 2-aminopurine, and
      functional assays indicate that the native P3, not alt P3, is present in the M
      state. The paradoxical behavior of alt P3 presumably arises because alt P3 biases
      folding toward M, but, after commitment to this folding pathway and before
      formation of M, alt P3 is replaced by P3. Further, structural and functional
      probes demonstrate that the misfolded ribozyme contains extensive native
      structure, with only local differences between the two states, and the misfolded
      structure even possesses partial catalytic activity. Despite the similarity of
      these structures, re-folding of M to the native state is very slow and is
      strongly accelerated by urea, Na+, and increased temperature and strongly impeded
      by Mg2+ and the presence of native peripheral contacts. The paradoxical
      observations of extensive native structure within the misfolded species but slow
      conversion of this species to the native state are readily reconciled by a model
      in which the misfolded state is a topological isomer of the native state, and
      computational results support the feasibility of this model. We speculate that
      the complex topology of RNA secondary structures and the inherent rigidity of RNA
      helices render kinetic traps due to topological isomers considerably more common
      for RNA than for proteins.

PMID- 16963082
TI  - Direct analysis of backbone-backbone hydrogen bond formation in protein folding
      transition states.
AB  - Here we investigate the role of backbone-backbone hydrogen bonding interactions
      in stabilizing the protein folding transition states of two model protein
      systems, the B1 domain of protein L (ProtL) and the P22 Arc repressor. A backbone
      modified analogue of ProtL containing an amide-to-ester bond substitution between
      residues 105 and 106 was prepared by total chemical synthesis, and the
      thermodynamic and kinetic parameters associated with its folding reaction were
      evaluated. Ultimately, these parameters were used in a Phi-value analysis to
      determine if the native backbone-backbone hydrogen bonding interaction perturbed
      in this analogue (i.e. a hydrogen bond in the first beta-turn of ProtL's beta
      beta-alpha-beta-beta fold) was formed in the transition state of ProtL's folding
      reaction. Also determined were the kinetic parameters associated with the folding
      reactions of two Arc repressor analogues, each containing an amide-to-ester bond
      substitution in the backbone of their polypeptide chains. These parameters were
      used together with previously established thermodynamic parameters for the
      folding of these analogues in Phi-value analyses to determine if the native
      backbone-backbone hydrogen bonding interactions perturbed in these analogues
      (i.e. a hydrogen bond at the end of the intersubunit beta-sheet interface and
      hydrogen bonds at the beginning of the second alpha-helix in Arc repressor's beta
      alpha-alpha structure) were formed in the transition state of Arc repressor's
      folding reaction. Our results reveal that backbone-backbone hydrogen bonding
      interactions are formed in the beta-turn and alpha-helical transition state
      structures of ProtL and Arc repressor, respectively; and they were not formed in
      the intersubunit beta-sheet interface of Arc repressor, a region of Arc
      repressor's polypeptide chain previously shown to have other non-native-like
      conformations in Arc's protein folding transition state.

PMID- 16963083
TI  - Structure of the Escherichia coli heptosyltransferase WaaC: binary complexes with
      ADP and ADP-2-deoxy-2-fluoro heptose.
AB  - Lipopolysaccharides constitute the outer leaflet of the outer membrane of Gram
      negative bacteria and are therefore essential for cell growth and viability. The
      heptosyltransferase WaaC is a glycosyltransferase (GT) involved in the synthesis
      of the inner core region of LPS. It catalyzes the addition of the first L-glycero
      D-manno-heptose (heptose) molecule to one 3-deoxy-D-manno-oct-2-ulosonic acid
      (Kdo) residue of the Kdo2-lipid A molecule. Heptose is an essential component of
      the LPS core domain; its absence results in a truncated lipopolysaccharide
      associated with the deep-rough phenotype causing a greater susceptibility to
      antibiotic and an attenuated virulence for pathogenic Gram-negative bacteria.
      Thus, WaaC represents a promising target in antibacterial drug design. Here, we
      report the structure of WaaC from the Escherichia coli pathogenic strain RS218
      alone at 1.9 A resolution, and in complex with either ADP or the non-cleavable
      analog ADP-2-deoxy-2-fluoro-heptose of the sugar donor at 2.4 A resolution. WaaC
      adopts the GT-B fold in two domains, characteristic of one glycosyltransferase
      structural superfamily. The comparison of the three different structures shows
      that WaaC does not undergo a domain rotation, characteristic of the GT-B family,
      upon substrate binding, but allows the substrate analog and the reaction product
      to adopt remarkably distinct conformations inside the active site. In addition,
      both binary complexes offer a close view of the donor subsite and, together with
      results from site-directed mutagenesis studies, provide evidence for a model of
      the catalytic mechanism.

PMID- 16963084
TI  - Structure of Aart, a designed six-finger zinc finger peptide, bound to DNA.
AB  - Cys2-His2 zinc fingers are one of the most common types of DNA-binding domains.
      Modifications to zinc-finger binding specificity have recently enabled custom DNA
      binding proteins to be designed to a wide array of target sequences. We present
      here a 1.96 A structure of Aart, a designed six-zinc finger protein, bound to a
      consensus DNA target site. This is the first structure of a designed protein with
      six fingers, and was intended to provide insights into the unusual affinity and
      specificity characteristics of this protein. Most protein-DNA contacts were found
      to be consistent with expectations, while others were unanticipated or
      insufficient to explain specificity. Several were unexpectedly mediated by
      glycerol, water molecules or amino acid-base stacking interactions. These results
      challenge some conventional concepts of recognition, particularly the finding
      that triplets containing 5'A, C, or T are typically not specified by direct
      interaction with the amino acid in position 6 of the recognition helix.

PMID- 16963085
TI  - Domain swapping in p13suc1 results in formation of native-like, cytotoxic
      aggregates.
AB  - The field of protein aggregation has been occupied mainly with the study of beta
      strand self-association that occurs as a result of misfolding and leads to the
      formation of toxic protein aggregates and amyloid fibers. However, some of these
      aggregates retain native-like structural and enzymatic properties suggesting
      mechanisms other than beta-strand assembly. p13suc1 is a small protein that can
      exist as a monomer or a domain-swapped dimer. Here, we show that, under native
      conditions, p13suc1 forms three-dimensional domain-swapped aggregates, and that
      these aggregates are cytotoxic. Thus, toxicity of protein aggregates is not only
      associated with beta-rich assemblies and amyloid fibers, involving non-native
      interactions, but it can be induced by oligomeric misassembly that maintains
      predominantly native-like interactions.

PMID- 16963086
TI  - Dcs2, a novel stress-induced modulator of m7GpppX pyrophosphatase activity that
      locates to P bodies.
AB  - The eukaryotic "scavenger" type decapping enzyme, an m(7)GpppX pyrophosphatase,
      is active in cellular mRNA metabolism and thereby influences posttranscriptional
      gene expression. The yeast version of this enzyme, Dcs1, catalyses cleavage of
      5'end m(7)G-oligoribonucleotide fragments generated by 3'-->5' exonucleolytic
      decay, and cleavage of m(7)GDP generated by Dcp1/Dcp2-mediated decapping in the
      5'-->3' decay pathway. We show that Dcs1 is active as a homodimer with low KM
      values for cleavage of m(7)GpppG (0.14 microM) and m(7)GDP (0.26 microM).
      Previous work showed that the paralogous DCS2 gene is transcriptionally induced
      via the amp-PKA pathway as yeast enters diauxie. The resulting Dcs2 protein forms
      a heterodimer together with Dcs1, both modulating Dcs1 substrate specificity and
      suppressing its k(cat). Since Dcs2 is recruited into cytoplasmic P bodies, its
      inhibitory function may be focused in these centres of mRNA storage/turnover.
      Dcs2 is therefore a novel type of stress-induced regulatory protein that
      modulates m(7)GpppX pyrophosphatase activity. Moreover, inhibition of Dcs1
      activity by Dcs2, like depletion of Dcs1, reduces chronological life span,
      possibly by modulating m(7)G misincorporation into nucleic acids. This could
      potentially link control of mRNA metabolism with senescence.

PMID- 16963087
TI  - Remission and cognitive ability in a cohort of patients with schizophrenia.
AB  - INTRODUCTION: Patients with schizophrenia were studied regarding their ability of
      achieving symptomatic remission. It was found that only approximately one-third
      of the patients fulfilled the criteria for remission. The importance of cognitive
      performance was studied to decide whether cognitive ability is a contributing
      factor for achieving remission. MATERIALS AND METHODS: A homogeneous cohort of
      211 patients, of whom 76 patients attained remission (36%), and 135 patients
      (64%) failed to, was studied. Remission was decided by the use of eight items
      from the PANSS in which none of these items should have a score above three
      points. The patients were also tested on a comprehensive battery of cognitive
      tests including vigilance, working memory, long-term memory, executive
      functioning, learning performance, visuomotor speed/efficacy, cognitive
      flexibility and pre-morbid functioning. RESULTS: Marked differences were
      exhibited in the cognitive abilities in all domains of patients who had attained
      remission in comparison with those who had not. DISCUSSION: This study highlights
      the importance of cognitive performance as one possible predictor of remission.
      Patients without remission had lower cognitive ability and may have more
      difficulty in benefiting from, or complying with their treatment. As a
      consequence, various forms of supportive treatment might increase the likelihood
      of remission.

PMID- 16963088
TI  - mGlu1 receptor blockade attenuates cue- and nicotine-induced reinstatement of
      extinguished nicotine self-administration behavior in rats.
AB  - Glutamatergic neurotransmission is believed to be critically involved in the
      acquisition and maintenance of drug addiction. The present study evaluated the
      role of metabotropic glutamate (mGlu) 1 receptors in the reinstatement of
      nicotine-seeking behavior. Rats were trained to nose-poke to receive response
      contingent intravenous infusions of nicotine (0.01 mg/kg/infusion, free base).
      Following the subsequent extinction phase, reinstatement tests were conducted in
      animals that were exposed either to response-contingent presentations of the
      nicotine-associated discrete light cues or to non-contingent nicotine priming
      injection (0.3mg/kg, s.c., salt) just prior to the test session. In a separate
      experiment, rats were subjected to the nearly identical response-reinstatement
      procedure but operant responding was established using food pellets instead of
      nicotine infusions. Pretreatment with the mGlu1 receptor antagonist EMQMCM
      (JNJ16567083, (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone
      methanesulfonate) significantly inhibited cue-induced reinstatement of nicotine
      seeking behavior (5 and 10, but not 2.5 mg/kg). EMQMCM (5 mg/kg) also prevented
      nicotine priming-induced reinstatement of nicotine-seeking behavior. At the
      highest tested dose only (10 mg/kg), EMQMCM attenuated cue-induced reinstatement
      of food-seeking behavior. Taken together with the previous reports, the present
      findings further suggest that blockade of mGlu1 receptors may be beneficial for
      preventing relapse to tobacco smoking in nicotine-dependent individuals.

PMID- 16963089
TI  - Chorda tympani nerve transection alters linoleic acid taste discrimination by
      male and female rats.
AB  - Taste is intimately associated with food choice, yet little is known about the
      role of taste in preferences for dietary fat, a major component of many foods. We
      measured the taste threshold for linoleic acid (LA), an essential free fatty acid
      found in dietary fat, before and after bilateral transections of the chorda
      tympani nerve (CTX) in adult male and female rats. We conditioned a taste
      aversion to 88 microM LA and assessed the generalization of the aversion to lower
      LA concentrations to determine LA discrimination thresholds. We discovered that
      female rats had a lower LA discrimination threshold (approximately 2.75 microM
      LA) than did male rats (approximately 11 microM LA). In another set of animals,
      we performed CTX and found that CTX elevated LA threshold to the same level
      (approximately 22 microM LA) in male and female rats. Finally, we evaluated
      licking responses to 11, 22, 44 and 88 microM LA mixed in sucrose by male rats
      and ovariectomized (OVX) female rats treated with estradiol benzoate or oil
      vehicle. All rats increased licking to increasing LA concentrations, but OVX rats
      responded to a lower LA concentration (22 microM) than did males (44 microM) in
      10-s trials. However, estradiol did not affect this outcome. Collectively, these
      experiments show that male and female rats use taste to discriminate LA and that
      the chorda tympani nerve, which innervates taste buds on the anterior tongue,
      plays a role in this discrimination. Furthermore, sex differences in fat
      preferences may depend on differences in fatty acid taste thresholds as well as
      on the taste stimuli with which fat is combined.

PMID- 16963090
TI  - Environmental factors influence on chemical polymorphism of the essential oils of
      Lychnophora ericoides.
AB  - Lychnophora ericoides is a Brazilian medicinal plant used in folk medicine as an
      anti-inflammatory and analgesic agent. The essential oils from leaves of two
      populations with and without scent, collected at 2-month intervals during an 1
      year period, were analysed by GC-MS. The results were submitted to principal
      component and cluster analysis which allowed two groups of essential oils to be
      distinguished with respect to sampling site and scent: cluster I (Vianopolis
      site, with specimens exhibiting an aromatic scent) containing a high percentage
      of alpha-bisabolol (44.7-76.4%) and alpha-cadinol (10.9-23.5%), and cluster II
      (Cristalina site, with specimens without scent) characterised by a high content
      of (E)-nerolidol (31.3-47.1%) and ar-dihydro-turmerone (4.8-15.4%). The canonical
      discriminant analysis showed that using the data set of the seven sampling months
      and (E)-nerolidol and alpha-bisabolol as predictable variables, it was possible
      to distinguish between the samples harvested according to Cerrado seasons, dry
      winter (May-September) and humid summer (November-March). In addition, canonical
      correlation analysis between the soil sampling sites and the populations revealed
      a significant relationship between oil components and edaphic factors. Oxygenated
      sesquiterpenes and potential acidity, Al saturation, cationic exchange capacity,
      silt, and sand load as the first canonical variate were fairly strongly related
      to samples collected in Vianopolis site. On the other hand, monoterpenes and
      sesquiterpene hydrocarbons were strongly related to chemical balance in soils
      (organic matter, P and base saturation), which is related to samples at the
      Cristalina site. The chemovariation observed appears to be environmentally
      determined.

PMID- 16963091
TI  - Metabolic profiling of in vitro micropropagated and conventionally greenhouse
      grown ginger (Zingiber officinale).
AB  - Ginger is an important medicinal and culinary herb, known worldwide for its
      health promoting properties. Because ginger does not reproduce by seed, but is
      clonally propagated via rhizome division and replanting, it is susceptible to
      accumulation and transmittance of pathogens from generation to generation. In
      addition, such propagation techniques lead to slow multiplication of particularly
      useful stocks. We have developed an in vitro propagation method to alleviate
      these problems. Metabolic profiling, using GC/MS and LC-ESI-MS, was used to
      determine if chemical differences existed between greenhouse grown or in vitro
      micropropagation derived plants. Three different ginger lines were analyzed. The
      constituent gingerols and gingerol-related compounds, other diarylheptanoids, and
      methyl ether derivatives of these compounds, as well as major mono- and
      sesquiterpenoids were identified. Principal component analysis and hierarchical
      cluster analysis revealed chemical differences between lines (yellow ginger vs.
      white ginger and blue ring ginger) and tissues (rhizome, root, leaf and shoot).
      However, this analysis indicated that no significant differences existed between
      growth treatments (conventional greenhouse grown vs. in vitro propagation derived
      plants). Further statistical analyses (ANOVA) confirmed these results. These
      findings suggest that the biochemical mechanisms used to produce the large array
      of compounds found in ginger are not affected by in vitro propagation.

PMID- 16963092
TI  - Secondary and tertiary isoquinoline alkaloids from Xylopia parviflora.
AB  - From the secondary and tertiary alkaloidal fractions of the root and the bark of
      Xylopia parviflora (Annonaceae), the isoquinoline alkaloids, 10,11-dihydroxy-1,2
      dimethoxynoraporphine and parvinine were isolated, along with 39 known alkaloids.
      Their structures were determined on the basis of analysis of spectroscopic data.

PMID- 16963093
TI  - Evaluation of synthetic repellents on mosquito nets in experimental huts against
      insecticide-resistant Anopheles gambiae and Culex quinquefasciatus mosquitoes.
AB  - Owing to the development of pyrethroid resistance in Anopheles gambiae, there is
      a need to develop chemical alternatives for use on mosquito nets. Synthetic
      insect repellents are widely used for personal protection as skin or clothing
      applications. The efficacy of repellent-treated nets (RTN) was evaluated in
      experimental huts in Cote d'Ivoire against pyrethroid-resistant populations of
      An. gambiae and Culex quinquefasciatus. The repellents tested were DEET (N,N
      diethyl-3-methylbenzamide) at 7.9 g/m2 and two formulations of ethyl
      butylacetylaminopropionate (IR3535) at 7.6 g/m2 and 7.3 g/m2. Over 45 nights
      there was a 74-82% reduction in the number of An. gambiae entering the huts
      containing RTNs but no significant reduction in entry of C. quinquefasciatus.
      There was a 63-64% reduction in the proportion of An. gambiae blood feeding but
      no reduction in the proportion of C. quinquefasciatus blood feeding in huts with
      RTNs. An unexpected result was the 69-76% mortality of An. gambiae and 51-61%
      mortality of C. quinquefasciatus in huts containing RTNs. Treated filter paper
      bioassays in WHO test kits confirmed that confined contact with DEET induces
      mortality. The DEET-based product provided better and longer protection; tunnel
      test bioassays confirmed that residual activity lasted for up to 6 weeks.
      Application of repellents to nets warrants further investigation and development.

PMID- 16963094
TI  - Phospholipase B activity and organophosphorus compound toxicity in cultured
      neural cells.
AB  - Organophosphorus compounds (OP) such as phenyl saligenin phosphate (PSP) and
      mipafox (MPX) which cause delayed neuropathy, inhibit neuropathy target esterase
      (NTE), while OPs such as paraoxon (PXN) react more readily with
      acetylcholinesterase. In yeast and mammalian cell lines, NTE has been shown to
      have phospholipase B (PLB) activity which deacylates intracellular
      phosphatidylcholine to glycerophosphocholine (GroPCho) and can be detected by
      metabolic labeling with [(14)C]choline. Here we investigated PLB activity in
      primary cultures of mouse neural cells. In cortical and cerebellar granule
      neurons and astrocytes, [(14)C]GroPCho labeling was inhibited by PSP and MPX:
      phenyl dipentylphosphinate (PDPP), a non-neuropathic NTE inhibitor, was more
      potent, while PXN, was substantially less so. In all three cell types, conversion
      of [(14)C]phosphatidylcholine to [(14)C]GroPCho over 24 h was relatively small
      (2.3-14%). Consequently, even with >80% inhibition of [(14)C]GroPCho production,
      increased [(14)C]phosphatidylcholine was not detected. At concentrations of 1-10
      microM, only PSP was cytotoxic to cortical and cerebellar granule neurons after
      24-h exposure. Moreover, dramatic changes in glial cell morphology were induced
      by PSP, but not PDPP or MPX, with rapid (2-3 h) rounding up of astrocytes and of
      Schwann cells in cultures of dissociated mouse dorsal root ganglia. We conclude
      that PLB activity is present in a variety of cultured mouse neural cell types but
      that acute loss of this activity is not cytotoxic. Conversely, the rapid toxic
      effects of PSP in vitro suggest that a serine hydrolase distinct from NTE is
      required continuously by neurons and glia.

PMID- 16963095
TI  - Cell-specific adaptation of two flaviviruses following serial passage in mosquito
      cell culture.
AB  - West Nile Virus (WNV) is a mosquito-borne flavivirus that was introduced into the
      U.S. in the New York City area in 1999. Despite its successful establishment and
      rapid spread in a naive environment, WNV has undergone limited evolution since
      its introduction. This evolutionary stability has been attributed to compromises
      made to permit alternating cycles of viral replication in vertebrate hosts and
      arthropod vectors. Outbreaks of a close relative of WNV, St. Louis encephalitis
      virus (SLEV), occur in the U.S. periodically and are also characterized by
      limited genetic change overtime. We measured both phenotypic and genotypic
      changes in WNV and SLEV serially passaged in mosquito cell culture in order to
      clarify the role of an individual host cell type in flavivirus adaptation and
      evolution. Genetic changes in passaged WNV and SLEV were minimal but led to
      increased relative fitness and replicative ability of the virus in the homologous
      cell line C6/36 mosquito cells. Similar increases were not measured in the
      heterologous cell line DF-1 avian cells. These phenotypic changes are consistent
      with the concept of cell-specific adaptation in flaviviruses.

PMID- 16963096
TI  - Molecular evolution of porcine circovirus type 2 genomes: phylogeny and
      clonality.
AB  - Porcine circoviruses (PCVs) type 1 (PCV1) and type 2 (PCV2) show high levels of
      nucleotide similarity, but PCV1 is considered non-pathogenic and PCV2 has been
      associated with several disease outcomes in pigs, mainly postweaning
      multisystemic wasting syndrome (PMWS). After exploring different topologies of
      the origin of PCVs, it was concluded that PCV1 and PCV2 seem to have a common
      origin. On the other hand, PCV2 could be divided into two groups (1 and 2) and
      eight clusters (1A to 1C and 2A to 2E), but none of those was apparently
      associated with disease status or geographic area. When phylogenetic trees
      constructed with the whole PCV2 genome, the cap or the rep genes were compared,
      some incongruence was identified. The possible existence of recombination was
      evaluated and cluster 1B was found to have a possible recombinant origin.
      Selective pressure was detected in all parts of the PCV2 genome, especially in
      the rep gene. Finally, the cap gene was the more suitable phylogenetic and
      epidemiological marker for PCV2, despite the fact that the virus can undergo
      recombination mainly within the first part of the rep region.

PMID- 16963097
TI  - Radial density distribution and symmetry of a Potexvirus, narcissus mosaic virus.
AB  - Narcissus mosaic virus is a Potexvirus, a member of the Flexiviridae family of
      filamentous plant viruses. Fiber diffraction patterns from oriented sols of
      narcissus mosaic virus have been used to determine the symmetry and structural
      parameters of the viral helix. The virions have a radius of 55+/-5 A. The viral
      helix has a pitch of 34.45+/-0.5 A, with 7.8 subunits per turn of the helix. We
      conclude that all members of the Potexvirus genus have close to 8 subunits per
      helical turn.

PMID- 16963098
TI  - Tomato spotted wilt virus Gc and N proteins interact in vivo.
AB  - Tomato spotted wilt virus (TSWV) virions consist of a nucleocapsid core
      surrounded by a membrane containing glycoproteins Gn and Gc. To unravel the
      protein interactions involved in the membrane acquisition of RNPs, TSWV
      nucleocapsid protein (N), Gn and Gc were expressed and analyzed in BHK21 cells.
      Upon coexpression of Gn, Gc and N, a partial colocalization of N with both
      glycoproteins was observed in the Golgi region. In contrast, upon coexpression of
      Gc and N in the absence of Gn, both proteins colocalized to a distinct non-Golgi
      perinuclear region. Using FLIM and FRET, interaction was demonstrated between N
      and Gc, but not between N and Gn, and was only observed in the region where both
      proteins accumulated. The genuine character of N-Gc interaction was confirmed by
      its presence in purified virus and RNP preparations. The results are discussed in
      view of TSWV particle assembly taking place at the Golgi complex.

PMID- 16963099
TI  - Synthesis, proteolytic processing and complex formation of N-terminally nested
      precursor proteins of the Rift Valley fever virus glycoproteins.
AB  - The genomic M RNA segment of Rift Valley fever virus is transcribed to produce a
      single mRNA with multiple translation initiation sites. The products of
      translation are an N-terminal nested series of polyproteins. These polyproteins
      enter the secretory system of the host cell and are proteolytically processed to
      yield the mature virion glycoproteins, Gn and Gc, and two non-structural
      glycoproteins. By means of pulse-chase immune precipitation experiments we
      identify the Gn and Gc precursor molecules and also show that signal peptidase
      cleavage is required for mature Gn and Gc production. We also demonstrate that a
      hydrophobic domain at the N-terminus of Gn acts as a signal peptide only in the
      context of the polyprotein precursors that initiate at the second, fourth or
      fifth AUGs. In addition, we document that formation of Gn/Gc heteromeric
      complexes occur rapidly (<5 min) and can occur prior to signal peptidase
      processing of Gn, suggesting that this complex forms in the endoplasmic
      reticulum. Interestingly, Gc can form a complex with a glycoprotein that has been
      considered nonstructural, a discovery that has implications for both the topology
      and potential packaging of this glycoprotein.

PMID- 16963100
TI  - Virus removal within a soil infiltration zone as affected by effluent
      composition, application rate, and soil type.
AB  - The column studies presented in this paper simulated the infiltrative surface of
      onsite wastewater systems where effluent is applied and where a biomat may form.
      Two bacteriophages, MS-2 and PRD-1, were used as surrogates for human pathogenic
      enteric viruses during two tracer tests. A vacuum manifold was used to simulate
      the drainage effects of an underlying unsaturated soil profile, allowing for the
      collection of percolate samples at 4 cm immediately below the infiltrative
      surface. The impact of effluent applied (septic tank effluent (STE) or a
      simulated ground water), soil type (medium sand or sandy loam), hydraulic loading
      rate (5 or 25 cm/day) and method of application (four equivalent daily doses or
      24 equivalent micro-doses per day) on the removal of viruses were investigated.
      These unsaturated mini column experiments demonstrated that the removal of
      viruses within an infiltrative surface zone (of approximately 4 cm) generally
      improved over time under the conditions studied. An exception occurred in sand
      filled columns dosed with STE where the removal of PRD-1 decreased after a period
      of effluent application. Statistical analysis conducted on the calculated percent
      removal demonstrated that the quality of the effluent applied to the infiltrative
      surface is important for removal of MS-2 and PRD-1. Hydraulic loading rate also
      proved important in the removal of viruses. At the time of tracer test 2, columns
      dosed at the higher HLR (25 cm/day) had higher percent removals for both MS-2 and
      PRD-1. Soil type altered the removal of PRD-1 at the time of the second tracer
      test, at which time sandy loam had higher removal rates for PRD-1. No significant
      differences were observed between columns dosed four times daily and those dosed
      24 times daily for either bacteriophage at either of the tracer test time points.
      These data suggest that over a relatively short period of operation the
      infiltrative surface of soil based wastewater treatment systems can achieve much
      higher removal then initially measured shortly after startup.

PMID- 16963101
TI  - The ageing effect on the bioaccessibility and fractionation of arsenic in soils
      from China.
AB  - Ingestion of contaminated soil has been recognized as an important exposure
      pathway of arsenic for humans, especially for children through outdoor hand-to
      mouth activities. An improved sequential extraction procedure was employed in an
      attempt to reveal the relationship between bioaccessibility and fractionation of
      As in five soils from China. Arsenic bioaccessibility in acidic ( approximately
      pH 4.5) soils reached approximately stable levels after a sharp decline within
      one week of ageing. In contrast, As bioaccessibility in higher pH (>6.0) soils
      was found to be significantly higher and took two weeks of ageing to reach stable
      levels. The artificially added As was more labile than indigenous As. The main
      proportions of added As were found in the specifically sorbed and amorphous and
      poorly-crystalline hydrous Fe/Al oxide-bound fractions. Correlation analysis
      shows that the non-specifically and specifically sorbed As are likely to
      constitute the main proportion of bioaccessible soil As. The soil content of
      amorphous and crystalline Fe/Al oxides and soil pH appear to be the key factors
      controlling, not only the time needed to reach a steady state, but also the
      magnitude of the bioaccessibility of As added to the soils.

PMID- 16963102
TI  - The fate of isoproturon in a freshwater microcosm with Lemna minor as a model
      organism.
AB  - Degradation, bioaccumulation and volatile loss of the 14C-labeled phenylurea
      herbicide isoproturon (IPU) was examined in a freshwater microcosm with the free
      floating macrophyte species Lemna minor during a 21-day exposure time.
      Isoproturon volatilisation was very low with 0.13+/-0.01% of the initially
      applied herbicide. Only a minor amount of the herbicide was completely
      metabolised, presumably by rhizosphere microorganisms and released as 14CO2. In
      total, about 9% isoproturon was removed from the aquatic medium during 21 days.
      The major portion of the pesticide was removed by bioaccumulation of Lemna minor
      (5.0+/-0.8%) and the bioconcentration factor (BCF) based on freshweight was
      15.8+/-0.2. However, this study indicated a high persistence of IPU in freshwater
      ecosystems and a potential hazard due to bioaccumulation in non-target species.
      The novel experimental system of this study, developed for easy use and multiple
      sampling abilities, enabled quantitatively studying the fate of isoproturon and
      showed high reproducibility with a mean average (14)C-recovery rate of 97.1+/
      0.7%.

PMID- 16963103
TI  - Effects of tributyltin on the energy metabolism of pen shell (Atrina pectinata
      japonica).
AB  - We examined the effects of tributyltin (TBT) on aerobic and anaerobic energy
      metabolism of pen shell (Atrina pectinata japonica). We exposed pen shells to TBT
      at nominal concentrations of 0 (control) and 1.0microg/l for 72h under aerobic
      condition. At the end of the exposure, half of the pen shells in each treatment
      were wrapped in plastic wrap to simulate exposure to hypoxia and held at 25
      degrees C for another 12h. The concentrations of the products of energy
      metabolism, namely lactate, pyruvate, fumarate and succinate, in adductor muscle
      were measured. The exposure to TBT under aerobic condition significantly elevated
      lactate, pyruvate and fumarate concentrations (p<0.001). After subsequent
      exposure to anaerobic condition, the mean concentration of succinate in the TBT
      treatment group was 64% of that in the control group, but there were no
      significant differences. Our results suggest that the energy metabolism of pen
      shell is disrupted by exposure to TBT.

PMID- 16963104
TI  - Thallium in fractions of soil formed on floodplain terraces.
AB  - Two soils formed on the floodplain terrace of a rivulet flowing through the zinc
      lead ore exploration area polluted with thallium and one soil from a floodplain
      terrace of the reference area were investigated in terms of thallium distribution
      between soil fractions. Such type of soil is formed on river floodplain terraces
      next to the main river channel and its composition records the history of river
      pollution. A sequential extraction of soil according to the BCR protocol was
      performed with an additional initial stage of extraction with water. Apart from
      labile thallium, thallium entrapped in the residual parent matter was also
      determined. Thallium was determined by flow-injection differential-pulse anodic
      stripping voltammetry. In all three cases, the major fraction is thallium
      entrapped in parent matter. Top soil from the polluted area contains 49.3%
      thallium entrapped in the residual parent matter, the bottom soil contains 41%
      while the reference soil contains 80% in this fraction. The major part of labile
      thallium is located in the reducible fraction (27.7% of total thallium in the top
      soil, 27% in the bottom soil and 12.4% of the reference soil). Second in terms of
      significance is the fraction of oxidizable thallium. The top soil contains 12% of
      total thallium concentration, the bottom soil contains 19% of total
      concentration, while the reference soil contains 4.1% of total concentration. The
      acid soluble/exchangeable fraction of thallium has almost the same significance
      as the oxidizable fraction. The top soil contains 10.4% of the total
      concentration, while the bottom soil contains 12% of the total concentration.
      Water soluble thallium concentration is very small. Comparison of the top and the
      bottom soil show that thallium has not been transported from the river channel
      onto the floodplain terrace over a long period.

PMID- 16963105
TI  - Transformation of phenol, catechol, guaiacol and syringol exposed to sodium
      hypochlorite.
AB  - Germs, xenobiotics and organic matter that influence the colour, turbidity and
      organoloeptic properties of water are removed by chlorination. Unfortunately,
      chlorine oxidants including sodium hypochlorite, used in water treatment induce
      processes that partly convert the treated compounds to unwanted chlorinated
      derivatives. The purpose of this work was to analyse the efficiency of
      transformation of phenol, catechol, guaiacol and syringol exposed to sodium
      hypochlorite and determine the intermediates formed during oxidative conversion
      of these compounds. The analysis was performed in aerobic conditions, both in
      acidic (pH 4.0) and alkaline (pH 8.0) medium. The effectiveness of transformation
      was slightly higher in acidic in comparison to alkaline conditions. Some
      chlorophenols, such as 2-chlorophenol, 2,4-dichlorophenol, 2,4,5-trichlorophenol
      and pentachlorophenol were determined as the products of phenol conversion.
      Chlorophenols were also formed during catechol, guaiacol and syringol
      transformation by replacement of hydroxy and methoxy residues by chlorine atoms.
      Moreover, some chlorocatechols and chlorinated methoxyphenols were determined
      during catechol and methoxyphenols transformations. Higher concentrations of
      chlorinated compounds were observed in the alkaline environment during phenol
      transformation. Conversion of catechol and methoxyphenols generated higher
      amounts of chlorinated intermediates in the acidic medium. In samples carboxylic
      acids like acetic and formic acids were determined. The formation of these
      compounds was the result of the cleavage of aromatic structure of phenols.

PMID- 16963106
TI  - Effects of sulfur dioxide, hydrogen peroxide and sulfuric acid on the de novo
      synthesis of PCDD/F and PCB under model laboratory conditions.
AB  - In a laboratory model system consisting of fly ash from municipal waste
      incinerator, CuCl2 x 2H2O, NaCl and activated carbon in N2 + 10% O2 atmosphere,
      the de novo synthetic reactions of formation of polychlorinated dibenzo-p-dioxins
      (PCDDs), dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) were studied
      under laboratory conditions in the presence of sulfur dioxide, hydrogen peroxide,
      and sulfuric acid. It has been found that the formation of PCDD is suppressed by
      sulfur dioxide more efficiently than the formation of PCDF. A similar effect has
      also been observed in the presence of hydrogen peroxide. The formation of PCDF is
      strongly suppressed in the presence of sulfuric acid. On the basis of the
      experimental results and thermodynamic calculations, the following mechanisms are
      proposed and discussed: oxidative destruction of PCDD and PCDF oxygen rings,
      conversion of cupric chloride and possibly also cupric oxide into the non
      reactive sulfate, and the Deacon oxychlorination processes catalyzed by cupric
      chloride.

PMID- 16963107
TI  - Diel cycles of arsenic speciation due to photooxidation in acid mine drainage
      from the Iberian Pyrite Belt (Sw Spain).
AB  - Twenty four hours diel cycles of arsenic speciation in Acid Mine Drainage (AMD)
      due to photooxidation have been reported for the first time. AMD samples were
      taken during 48 h (31st March and 1st April, 2005) at 6 h intervals from the
      effluent of a massive abandoned polymetallic sulphide mine of the Iberian Pyrite
      Belt (Sw Spain). Samples were preserved in situ using cationic exchange prior to
      analysis by coupled high performance liquid chromatography, hydride generation
      and atomic fluorescence spectrometry (HPLC-HG-AFS) for arsenic speciation. The
      results indicated the presence of inorganic arsenic species with daily means of
      262mugl(-1) for As(V) and 107 microg l(-1) for As(III). No marked diel trend was
      observed for As(V). However, a marked diel trend was observed for As(III) in the
      two studied days, with maximum concentrations during nighttime (141-143 microg l(
      1)) and minimum concentrations at daytime (72-77 microg l(-1)). This difference
      in concentration during daytime and nighttime is ca. 100%. A similar diel cycle
      was observed for iron. An explanation for the arsenic diel cycles observed is the
      light induced photooxidation of As(III) and the elimination of As(V) due to its
      adsorption onto Fe precipitates during the daytime. Furthermore, the diel changes
      in arsenic speciation emphasize the importance of designing suitable sampling
      strategies in AMD systems.

PMID- 16963108
TI  - Trabecular bone ontogeny in the human proximal femur.
AB  - Ontogenetic changes in the human femur associated with the acquisition of bipedal
      locomotion, especially the development of the bicondylar angle, have been well
      documented. The purpose of this study is to quantify changes in the three
      dimensional structure of trabecular bone in the human proximal femur in relation
      to changing functional and external loading patterns with age. High-resolution X
      ray computed tomography scan data were collected for 15 juvenile femoral
      specimens ranging in age from prenatal to approximately nine years of age. Serial
      slices were collected for the entire proximal femur of each individual with voxel
      resolutions ranging from 0.017 to 0.046 mm depending on the size of the specimen.
      Spherical volumes of interest were defined within the proximal femur, and the
      bone volume fraction, trabecular thickness, trabecular number, and fabric
      anisotropy were calculated in three dimensions. Bone volume fraction, trabecular
      number, and degree of anisotropy decrease between the age of 6 months and 12
      months, with the lowest values for these parameters occurring in individuals near
      12 months of age. By age 2-3 years, the bone volume, thickness, and degree of
      anisotropy increase slightly, and regions in the femoral neck become more
      anisotropic corresponding to the thickening of the inferior cortical bone of the
      neck. These results suggest that trabecular structure in the proximal femur
      reflects the shift in external loading patterns associated with the initiation of
      unassisted walking in infants.

PMID- 16963109
TI  - Whole blood mercury and selenium concentrations in a selected Austrian
      population: does gender matter?
AB  - BACKGROUND: Data on mercury exposure of the Austrian population were inadequate.
      This study was performed to determine the causal factors underlying mercury
      exposure and selenium concentrations, and to estimate the gender-related health
      impacts. METHODOLOGY: Venous blood samples of 78 women and 81 men were drawn at
      the Austrian Red Cross, Vienna. Mercury contents in acid-digested whole blood
      samples were measured after amalgam enrichment by CV-AAS, and selenium by AAS
      (heated quartz-cell) after hydrid formation. RESULTS: The average total mercury
      blood content of Austrians was low (2.38+/-1.55 microgL(-1); N=152). Mercury and
      selenium concentrations were not different between the genders (P>0.05) but we
      observed discrepancies regarding the causal factors. Mercury levels in men were
      influenced not only by fish consumption but also by age, education level, and
      amalgam fillings, whereas in women, only the diet (fish/seafood, red wine
      consumption) determined blood mercury (P<0.05). Moreover, only the males
      indicated a depressive effect of dental amalgam on hematocrit (P<0.05). Regarding
      selenium, age and alcohol consumption led to lower concentrations in men, whereas
      a high-level education had the opposite effect; no determinant was found for
      women. For the whole study group, a significant effect of chronic disease on
      selenium levels could be detected (P<0.05). 18% of women and 13% of men showed
      marginal selenium deficiency (blood selenium<65 microgL(-1)). Selenium and
      mercury concentrations were not correlated. CONCLUSIONS: Our results indicate the
      need to evaluate and integrate gender-related findings in metal toxicology and
      trace element research, because different causal factors require different
      preventive measures to reduce mercury exposure and the risk of low selenium
      concentrations. Future research is needed on the gender- and age-related
      differences in fish/seafood consumption habits, the modifications of mercury
      toxicokinetics through sex hormones, the selenium supply in Austria, and the
      clinical relevance of a low selenium status.

PMID- 16963110
TI  - Localization of group-1 allergen Zea m 1 in the coat and wall of maize pollen.
AB  - The pollen surface consists of an outermost coat and an underlying wall. It makes
      the initial contact with the stigma surface during sexual reproduction. To date,
      only two proteins have been identified from the maize pollen coat. Zea m 1 (beta
      expansin 1) is the major group-1 allergen in maize pollen, but its presence and
      localization in the pollen coat and wall has not yet been explored. In the
      present study, immunoblot analysis using an antibody directed against group-1
      allergen revealed that a small amount of Zea m 1 exists in the pollen coat
      fraction prepared using a diethyl ether wash. Immunogold labeling also showed
      that the extracellular localization of Zea m 1 was mainly restricted to the
      tectum and the foot layer of the exine (the outer pollen wall), and gold
      particles immunolabelling Zea m 1 were unevenly dispersed throughout the pollen
      coat and wall. Moreover, a substantial amount of Zea m 1 was localized in the
      cytoplasm of the pollen interior. The presence of Zea m 1 in the pollen coat and
      wall suggests that Zea m 1 may play a potential role in pollen germination on the
      stigma.

PMID- 16963111
TI  - Lymphatic mapping and sentinel node biopsy in women with high-risk endometrial
      cancer.
AB  - OBJECTIVE: To evaluate fundal injection of blue dye and radiocolloid for
      lymphatic mapping and sentinel node identification in women with high-risk
      endometrial cancer. METHODS: At laparotomy, 18 women with high-risk endometrial
      cancer had isosulfan blue and technitium-99 radiocolloid injected into the
      uterine fundus subserosally. Sentinel nodes were then identified either by direct
      observation of blue dye, by radioactive counts using a handheld gamma counter, or
      by a combination of both methods. The number and location of sentinel node(s)
      were recorded and compared with the final lymph node specimens after hysterectomy
      and selective lymphadenectomy. RESULTS: A sentinel node was identified in only 8
      (45%) of the cases. Four patients had sentinel nodes only in the pelvis, 2 had
      sentinel nodes in the pelvis and above the bifurcation of the aorta, and 2
      patients had sentinel nodes above the bifurcation of the aorta only. Seven (88%)
      patients had unilateral drainage of dye and the radiocolloid; the other patient
      had bilateral drainage. No patients had metastatic disease to sentinel or
      nonsentinel lymph nodes. CONCLUSIONS: Subserosal fundal injection of blue dye and
      the radiocolloid is a poor technique for identifying sentinel lymph nodes in
      patients with high-risk endometrial cancer.

PMID- 16963112
TI  - EGFR expression is associated with groin node metastases in vulvar cancer, but
      does not improve their prediction.
AB  - OBJECTIVES: High morbidity of elective inguinofemoral lymphadenectomy in early
      stage vulvar cancer patients urges the need for defining a group of low-risk
      patients in whom inguinofemoral lymphadenectomy can be safely omitted. Aim of the
      study was to evaluate whether in addition to 'classic' clinicopathological
      factors determination of EGFR expression in vulvar cancer can be helpful in
      defining such a 'low-risk' group. METHODS: Formalin-fixed paraffin-embedded tumor
      tissue samples of 197 surgically treated T1/2 patients were collected in a Tissue
      Micro Array (TMA). On this TMA, immunohistochemistry for EGFR was performed.
      Logistic regression analyses were performed including histopathological
      characteristics with the presence of nodal metastases as outcome. A predictive
      model was constructed, and absolute risks were calculated. RESULTS: EGFR
      expression was present in 68% of the vulvar tumors and related to the presence of
      lymph node metastases (OR 2.12, 95% CI 1.09-4.10). Our predictive model with only
      clinicopathological factors was able to define a group of patients with a
      likelihood of absence of lymph node metastases of 13% (95% CI 5-36), which could
      be decreased to 6% (95% CI 0-29) after inclusion of EGFR expression (p=0.07).
      CONCLUSIONS: EGFR expression is present in the majority of vulvar tumors and is
      associated with groin node metastases in vulvar cancer. Current classic
      clinicopathological predictive factors for inguinofemoral lymph node metastases
      with or without EGFR analysis are not strong enough for identification of
      "sufficiently low" risk T1/2 vulvar cancer patients. Our predictive model
      approach however is excellent for evaluation of new cell biological parameters,
      associated with clinical outcome.

PMID- 16963113
TI  - NMDA antagonist AP-5 increase environmentally induced cocaine-conditioned
      locomotion within the nucleus accumbens.
AB  - An environment previously associated with cocaine use can elicit cravings, even
      in the absence of the drug, which may be due to the formation of strong
      associations between the environment and the drug. These associations can result
      from motor learning and reinforcing effects of cocaine, and may be mediated in
      part by ionotropic glutamate receptors in the nucleus accumbens (N.Acc.). To
      determine whether NMDA receptor activity in the N.Acc. affects the expression of
      conditioned locomotion, rats were trained using an environment-elicited cocaine
      conditioning paradigm. Rats trained to pair a cocaine injection with an
      environment showed an increased locomotor activity when tested in the drug-paired
      environment, whereas rats injected with cocaine in their home cages did not
      exhibit greater locomotion. Significantly greater locomotor activity occurred in
      trained animals that received an infusion of AP-5, a NMDA receptor antagonist,
      into the N.Acc. These results suggest that animals trained to associate
      environmental cues with cocaine become conditioned to this environment.
      Furthermore, our finding demonstrates that NMDA receptor activation within the
      N.Acc. modulates cocaine-induced conditioning.

PMID- 16963114
TI  - Cryopreservation of immature and in vitro matured porcine oocytes by solid
      surface vitrification.
AB  - Cryopreservation of normal, lipid-containing porcine oocytes has had limited
      practical success. This study used solid surface vitrification (SSV) of immature
      germinal vesicle (GV) and mature meiosis II (MII) porcine oocytes and evaluated
      the effects of pretreatment with cytochalasin B, cryoprotectant type
      (dimethylsulfoxide (DMSO), ethylene glycol (EG), or both), and warming method
      (two-step versus single-step). Oocyte survival (post-thaw) was assessed by
      morphological appearance, staining (3',6'-diacetyl fluorescein), nuclear
      maturation, and developmental capacity (after in vitro fertilization). Both GV
      and MII oocytes were successfully vitrified; following cryopreservation in EG,
      more than 60% of GV and MII stage porcine oocytes remained intact (no significant
      improvement with cytochalasin B pretreatment). Oocytes (GV stage) vitrified in
      DMSO had lower (P<0.05) nuclear maturation rates (31%) than those vitrified in EG
      (51%) or EG+DMSO (53%). Survival was better with two-step versus single-step
      dilution. Despite high survival rates, rates of cleavage (20-26%) and blastocyst
      formation (3-9%) were significantly lower than for non-vitrified controls (60 and
      20%). In conclusion, SSV was a very simple, rapid, procedure that allowed normal,
      lipid-containing, GV or MII porcine oocytes to be fertilized and develop to the
      blastocyst stage in vitro.

PMID- 16963115
TI  - Genetic variation in fertility of heat-stressed male mice.
AB  - The damaging effects of heat stress on male fertility are evident in developing
      spermatozoa expressed in ejaculates 18-28 days post-stress in mice. Our
      objectives were to: (1) assess genetic variation in fertility of heat-stressed
      male mice and (2) determine response to selection for fertility after heat stress
      in male mice. Mature male mice were exposed to heat stress (35+/-1 degrees C;
      n=50) or control (21+/-1 degrees C; n=10) conditions for 24h (day 0) and then
      hemicastrated for tissue collection. Two periods of mating tests followed, period
      1 (from days 3 to 11) when no reductions in fertility were anticipated, and
      period 2 (days 18-26) when variation in fertility was expected. Period 2 pregnant
      females were sacrificed in late gestation. Males were indexed by multiplying
      overall mean ovulation rate by pre-implantation survival and number of pregnant
      period 2 mates. The five highest and five lowest ranking males were identified as
      heat stress resistant and susceptible, respectively. Resistant males were
      61.2units superior in the index, 57.5% greater in pregnancy rate, and 57.6 total
      fetuses greater than susceptible males. Progeny of resistant sires were superior
      to progeny of susceptible sires in estimated breeding value by 4.5units for the
      index, 4.1% for pregnancy rate, and 5.2 fetuses (P<0.0001). Heritability
      estimates for the index, pregnancy rate, and number of fetuses ranged from 0.09
      to 0.13, suggesting male fertility following heat stress is heritable and
      responds to selection.

PMID- 16963116
TI  - Surface modification of poly(hydroxybutyrate) films to control cell-matrix
      adhesion.
AB  - Tailoring surface properties of degradable polymer scaffolds is key to progress
      in various tissue engineering strategies. Poly(3-hydroxybutyrate) and poly(3
      hydroxybutyrate-co-4-hydroxybutyrate) thin films were modified by low pressure
      ammonia plasma, low pressure water vapour plasma, or immersion in a sodium
      hydroxide solution to elaborate means to control the cell-matrix adhesion of
      human umbilical cord vein endothelial cells grown on these materials. Fibronectin
      (FN) heteroexchange and cell adhesion were correlated to the physicochemical
      characteristics of the modified polymer surfaces which were investigated by X-ray
      photoelectron spectroscopy (XPS), scanning force microscopy (SFM), electrokinetic
      measurements, and contact angle measurements. All treatments increased the
      hydrophilicity of the polymer samples, which could be accounted to newly created
      amine or carboxyl functionalities for ammonia plasma or water vapour plasma
      treatments, respectively, and ester hydrolysis for treatments with alkaline
      aqueous solutions. Main features of cell adhesion and FN reorganisation-evaluated
      after 1h and after 5 days-could be attributed to the anchorage strength of pre
      coated FN layers at the polymer surface, which was, in turn found to be triggered
      by the type of modification applied. In line with earlier studies referring to
      different materials cell adhesion and matrix reorganisation were shown to be
      sensitively controlled through the physicochemical profile of
      poly(hydroxybutyrate) surfaces.

PMID- 16963117
TI  - Enrichment of osteogenic cell populations from rat bone marrow stroma.
AB  - The presence of multiple cell types in bone marrow and their varying proportions
      from isolation to isolation may count for the considerable variation in the
      outcome of different experiments. The presence of these multiple subpopulations
      suggests a need for a method that can purify the osteogenic component, i.e.
      osteoprogenitors, from other components. The availabilities of monoclonal
      antibodies recognizing subpopulations of osteoblasts are providing means for
      antibody-based methods. The cell surface antigens STRO-1, ALP and HOP-26 were
      used for cell sorting experiments with fluorescence activated cell sorting
      (FACS). These cell populations were analyzed on differential gene expression,
      cell proliferation and differentiation into the osteoblastic lineage. The oligo
      microarray results showed that only the ALP positive cell population expressed
      genes of the extracellular matrix; like different collagens, ECM-1 and matrix
      protease MMP-14. The real-time polymerase chain reaction (QPCR) results showed
      that STRO-1 and ALP positive cells had an upregulation in expression of
      lipoprotein lipase, osteocalcin, and collagen type I. Integrin beta-3 was only
      upregulated for ALP positive cells, while for these cells downregulation occurred
      for the genes myosine, alkaline phosphatase and integrin beta-1. HOP-26 positive
      cells showed an upregulation in collagen type I compared to control group. The
      DNA analysis revealed that the cells of the control group and the HOP-26 positive
      cells showed a 5 times higher cell growth compared to the STRO-1 and ALP positive
      cells. The alkaline phosphatase activity showed no activity for the control
      group. The STRO-1 and ALP positive cells had a higher activity compared to the
      HOP-26 positive. The calcium measurements revealed only for the control group
      calcium at day 24. Based on the results of our study, we conclude that the FACS
      method had no negative effect on the proliferating as well as differentiating
      response of the cells. Further, we conclude that by using an antibody-based cell
      selection method, different cell populations with different mRNA expression
      profiles and different osteogenic characteristics can be obtained.

PMID- 16963118
TI  - The mechanical properties and osteoconductivity of hydroxyapatite bone scaffolds
      with multi-scale porosity.
AB  - The relative osteoconductivity and the change in the mechanical properties of
      hydroxyapatite (HA) scaffolds with multi-scale porosity were compared to
      scaffolds with a single pore size. Non-microporous (NMP) scaffolds contained only
      macroporosity (250-350 microm) and microporous (MP) scaffolds contained both
      macroporosity and microporosity (2-8 microm). Recombinant human bone
      morphogenetic protein-2 (rhBMP-2) was incorporated into all scaffolds via gelatin
      microspheres prior to implantation into the latissimus dorsi muscle of Yorkshire
      pigs. After 8 weeks, only the MP scaffolds contained bone. The result
      demonstrates the efficacy of the MP scaffolds as drug carriers. Implanted and as
      fabricated scaffolds were compared using histology, microcomputed tomography,
      scanning electron microscopy, and compression testing. Implanted scaffolds
      exhibited a stress-strain response similar to that of cancellous bone with
      strengths between those of cancellous and cortical bone. The strength and
      stiffness of implanted NMP scaffolds decreased by 15% and 46%, respectively.
      Implanted MP scaffolds lost 30% of their strength and 31% of their stiffness.
      Bone arrested crack propagation effectively in MP scaffolds. The change in
      mechanical behavior is discussed and the study demonstrates the importance of
      scaffold microporosity on bone ingrowth and on the mechanical behavior of HA
      implant materials.

PMID- 16963119
TI  - The effect of heparin-functionalized PEG hydrogels on three-dimensional human
      mesenchymal stem cell osteogenic differentiation.
AB  - Poly(ethylene glycol) (PEG) hydrogels functionalized with heparin were utilized
      as a three-dimensional culture system for human mesenchymal stem cells (hMSCs).
      Heparin-functionalized hydrogels supported hMSC viability, as quantified through
      live/dead imaging, and induced osteogenic differentiation, as measured by
      increased alkaline phosphatase (ALP) production and osteopontin (OPN) and
      collagen I (COL I) gene expression over the 5-week study. Further exploration of
      the potential mechanism of heparin-induced osteogenic differentiation was
      performed. Specifically, the availability of bone morphogenetic protein 2 (BMP2)
      and fibronectin (FN) in the culture system was controlled and hMSC osteogenic
      differentiation was evaluated as a function of the microenvironment. BMP2
      availability increased both ALP production and OPN gene expression, while FN
      increased ALP production, but not OPN gene expression. Furthermore,
      immunostaining of integrin expression revealed that viability and differentiation
      were differentially affected by integrin production, where both alpha5beta1 and
      alphavbeta3 integrin-ligand interactions supported viability, while only the
      alpha5beta1 integrin played a role in hMSC osteogenic differentiation.

PMID- 16963120
TI  - KN-62 analogues as potent differentiating agents of HL-60 cells.
AB  - KN-62, an inhibitor of the calmodulin-dependent protein kinases (CaMKs), enhances
      the terminal differentiation of retinoic acid sensitive human myeloid leukemia
      cell lines. In an effort to identify additional CaMK inhibitors that exhibit more
      potent activity in triggering leukemia cell differentiation, we synthesized 45
      analogues of KN-62 and determined their ability to induce HL-60 cell
      differentiation. Sixteen of these novel analogues exhibited significant
      differentiation-inducing activity, and one analogue, AS-004, was five times more
      potent than KN-62 in inhibiting proliferation and inducing differentiation of HL
      60 cells. Such KN-62 analogues and/or related compounds may prove useful in
      treating promyelocytic leukemia.

PMID- 16963121
TI  - The Ca(v)2.3 voltage-gated calcium channel in epileptogenesis--shedding new light
      on an enigmatic channel.
AB  - The Ca(v)2.3 encoded Ca2+ channel is probably one of the least well-understood
      voltage-gated calcium channels in terms of physiology, pharmacology and clinical
      relevance. Here we provide a detailed insight into the functional involvement of
      Ca(v)2.3 in etiology and pathogenesis of both convulsive and non-convulsive
      seizures. In the CNS, Ca(v)2.3 containing E/R-type Ca2+ channels are involved in
      triggering epileptiform discharges by significantly contributing to plateau
      potentials and afterdepolarisations. Pharmacological analysis further revealed
      that various antiepileptic drugs specifically target Ca(v)2.3 VGCCs capable of
      blocking epileptiform burst activity. Whereas electroencephalographic recordings
      in Ca(v)2.3-/- mice did not reveal any ictal-like discharges, seizure
      susceptibility was dramatically reduced in Ca(v)2.3-/- animals compared to
      controls, further supporting the observation that Ca(v)2.3 is an important factor
      in triggering epileptiform activity in neuronal populations. Although some
      aspects of its relationship to epilepsy have been uncovered, further functional
      characterization of Ca(v)2.3 in etiology and pathogenesis of human epileptic
      syndromes as well as development of new antiepileptic drugs specifically
      targeting Ca(v)2.3 turns out to become indispensable.

PMID- 16963122
TI  - Synthesis, structural characterization and influence on the phagocytic activity
      of human neutrophils of thiazoline and thiazine derivative ligands and their
      zinc(II) complexes.
AB  - The zinc(II) complexes dichloro[2-(3,4-dichlorophenyl)imino-kappaN-(2-thiazolin
      kappaN-2-yl)thiazolidine]zinc(II) (1) and dichloro[2-(3,4-dichlorophenyl)imino
      kappaN-(4H-5,6-dihydro-1,3-thiazin-kappaN-2-yl)tetrahydrothiazine]zinc(II) (2)
      have been isolated and characterized in the solid state by X-ray diffraction,
      elemental analysis and IR spectra. In both complexes, the environment around the
      zinc(II) ion may be described as a distorted tetrahedral geometry, with the
      metallic atom coordinated to two chlorine atoms [Zn-Cl(1)=2.218(1)A; Zn
      Cl(2)=2.221(1)A], one imino nitrogen [Zn-N(3)=2.042(2)A] and one thiazoline
      nitrogen [Zn-N(1)=2.022(2)A] in complex 1 and to two chlorine atoms [Zn
      Cl(1)=2.216(1)A; Zn-Cl(2)=2.192(1)A], one imino nitrogen [Zn-N(3)=2.045(2)A] and
      one thiazine nitrogen [Zn-N(1)=2.039(2)A] in complex 2. In addition, we also
      report in this study the crystal structure of the 2-(3,4-dichlorophenyl)imino-N
      (2-thiazolin-2-yl)thiazolidine (TdTn) ligand as well as the synthesis and
      characterization by X-ray diffraction, (1)H and (13)C NMR spectra, elemental
      analysis, IR and electronic spectra of the 2-(3,4-dichlorophenyl)imino-N-(4H-5,6
      dihydro-1,3-thiazin-2-yl)tetrahydrothiazine (TzTz) ligand. Besides, we study the
      phagocytic function in humans neutrophils treated with each complex and ligand
      aforementioned.

PMID- 16963123
TI  - Reduction of plastocyanin by tyrosine-containing oligopeptides.
AB  - Oxidized plastocyanin (PC) was reduced with TyrTyrTyr and LysLysLysLysTyrTyrTyr
      (KKKKYYY) oligopeptides at neutral pH. The TyrTyrTyr site of the peptides
      provided an electron to the copper active site of PC, whereas the tetralysine
      site of KKKKYYY functioned as the recognition site for the negative patch of PC.
      The reciprocal initial rate constant (1/k(int)) increased linearly with the
      reciprocal TyrTyrTyr concentration and proton concentration, although the
      electron transfer rate decreased gradually with time. The results showed that PC
      was reduced by the deprotonated species of TyrTyrTyr. A linear increase of log
      k(int) with increase in the ionic strength was observed due to decrease in the
      electrostatic repulsion between negatively charged PC and deprotonated
      (TyrTyrTyr)(-). PC was reduced faster by an addition of KKKKYYY to the PC
      TyrTyrTyr solution, although KKKKYYY could not reduce PC without TyrTyrTyr. The
      ESI-LCMS spectrum of the products from the reaction between PC and TyrTyrTyr
      showed molecular ion peaks at m/z 1015.7 and 1037.7, which suggested formation of
      a dimerized peptide that may be produced from the reaction of a tyrosyl radical.
      The results indicate that PC and the tyrosine-containing oligopeptides form an
      equilibrium, PC(ox)/(oligopeptide)(-)-->/<--PC(red)/(oligopeptide)(*). The
      equilibrium is usually shifted to the left, but could shift to the right when the
      produced oligopeptide radical reacts with unreacted peptides. For the reaction of
      PC with KKKKYYY in the absence of TyrTyrTyr, the produced KKKK(YYY)(*) radical
      peptide could not react with other KKKKYYY peptides, since they were positively
      charged. In the presence of both KKKKYYY and TyrTyrTyr, PC may interact
      effectively with KKKKYYY through its tetralysine site and receive an electron
      from its TyrTyrTyr site, where the produced KKKK(YYY)(*) may interact with
      TyrTyrTyr peptides.

PMID- 16963124
TI  - Lipids in photosynthetic reaction centres: structural roles and functional holes.
AB  - Photosynthetic proteins power the biosphere. Reaction centres, light harvesting
      antenna proteins and cytochrome b(6)f (or bc(1)) complexes are expressed at high
      levels, have been subjected to an intensive spectroscopic, biochemical and
      mutagenic analysis, and several have been characterised to an informatively high
      resolution by X-ray crystallography. In addition to revealing the structural
      basis for the transduction of light energy, X-ray crystallography has brought
      molecular insights into the relationships between these multicomponent membrane
      proteins and their lipid environment. Lipids resolved in the X-ray crystal
      structures of photosynthetic proteins bind light harvesting cofactors, fill intra
      protein cavities through which quinones can diffuse, form an important part of
      the monomer-monomer interface in multimeric structures and may facilitate
      structural flexibility in complexes that undergo partial disassembly and repair.
      It has been proposed that individual lipids influence the biophysical properties
      of reaction centre cofactors, and so affect the rate of electron transfer through
      the complex. Lipids have also been shown to be important for successful
      crystallisation of photosynthetic proteins. Comparison of the three types of
      reaction centre that have been structurally characterised reveals interesting
      similarities in the position of bound lipids that may point towards a generic
      requirement to reinforce the structure of the core electron transfer domain. The
      crystallographic data are also providing new opportunities to find molecular
      explanations for observed effects of different types of lipid on the structure,
      mechanism and organisation of reaction centres and other photosynthetic proteins.

PMID- 16963125
TI  - Electrical high frequency stimulation of the caudate nucleus induces local GABA
      outflow in freely moving rats.
AB  - Electrical high frequency stimulation of the globus pallidus internus or the
      subthalamic nucleus has beneficial motor effects in advanced Parkinson's disease.
      The mechanisms underlying these clinical results remain, however, unclear. From
      previous in vitro studies it is proposed that the gamma-aminobutyric acid (GABA)
      system is involved in the effectiveness of electrical high frequency stimulation
      (HFS). In these experiments, we developed an in vivo model that allows for
      simultaneous and collocated microdialysis and HFS by electrical pulses of 124 Hz
      in the caudate nucleus of freely moving rats. GABA and glutamate outflow were
      sampled by microdialysis technique and quantified after pre-column o
      phthaldialdehyde sulphite derivatization using HPLC with electrochemical
      detection. As the most outstanding result, we could demonstrate that high
      frequency stimulation significantly increased basal GABA outflow without
      affecting glutamate levels in freely moving rats.

PMID- 16963126
TI  - Non-pharmacological treatments in the management of rapid cycling bipolar
      disorder.
AB  - BACKGROUND: Rapid cycling (RC) bipolar disorder is often treatment-resistant to
      pharmacotherapy. Non-pharmacological methods, however, are reasonable
      considerations in treatment refractory cases of bipolar patients. Thus, such
      methods may be useful in the management of RC, especially when drugs are not
      shown to be effective. METHOD: This review is based on studies of all major non
      pharmacological methods which are used in the management of bipolar disorder, by
      focusing on data regarding patients with a RC pattern of the illness. RESULTS:
      Regarding biological treatments, for electroconvulsive therapy and sleep
      deprivation, there exists some evidence that they might be efficacious in RC
      patients for acute treatment as well as for prophylaxis from recurrences. Light
      therapy has not been shown to be efficacious in RC, while no published data exist
      for transcranial magnetic stimulation and vagus nerve stimulation. The non
      biological treatments include psychotherapeutic and psychosocial interventions;
      these have not been tried particularly on RC patients, but their use should be
      expected to contribute to the overall management of the RC pattern as it does to
      that of mood disorder in general. LIMITATIONS: Many data on which this review is
      based are drawn from case reports or non-randomised trials. CONCLUSIONS: Non
      pharmacological methods, either biological or non-biological (psychotherapies and
      psychoeducation), may be applied in the management of RC patients. These methods
      might be used in combination with the administration of drug treatment, based on
      the clinical experience of the physician and the individual characteristics of
      the patient.

PMID- 16963127
TI  - Altered expression of interleukin-18 in the ectopic and eutopic endometrium of
      women with endometriosis.
AB  - OBJECTIVE: This study has investigated the expression of interleukin (IL)-18 in
      the eutopic and ectopic endometrium of women with endometriosis and the role of
      IL-18 on the pathogenesis of endometriosis. METHODS: Endometriotic tissue
      specimens and endometrium specimens were obtained from patients with
      endometriosis. IL-18 protein was determined by immunohistochemical analysis.
      Expression levels of IL-18 mRNA were analyzed by reverse transcriptase (RT)-PCR.
      RESULTS: IL-18 was detected in the glandular epithelial and stromal cells of
      eutopic and ectopic endometrium. RT-PCR analysis showed that endometrial IL-18
      mRNA expression levels were significantly higher at the secretory phase than the
      proliferative phase in normal women, but not in patients with endometriosis. IL
      18 mRNA expression levels were lower in the ectopic endometrium than in the
      eutopic endometrium of women with endometriosis. IL-18 mRNA levels in both
      ectopic and eutopic endometrium of patients with endometriosis were lower than in
      endometrium of women without endometriosis. CONCLUSION: Ectopic and eutopic
      endometrial IL-18 was down-regulated in women with endometriosis, suggesting that
      IL-18 might play a pathogenic role in the formation of endometriosis.

PMID- 16963128
TI  - T cell homeostasis in steady state and lymphopenic conditions.
AB  - Homeostasis in the immune system is an important principle ensuring that the
      numbers of peripheral lymphocytes are kept more or less constant despite numerous
      disturbances in the immune system during the lifetime of an organism. Mechanisms
      relating to maintenance of homeostasis have mainly been investigated in
      experimental systems exhibiting extreme lymphopenic conditions in which the
      behavior of adoptively transferred lymphocytes is assessed in the absence of
      endogenous lymphocytes. While these experimental systems have yielded important
      insight into mechanisms that shape the survival and expansion potential of T
      cells, their extrapolation to normal steady state conditions that do not involve
      extreme lymphopenia has sometimes been difficult. We review here the different
      scenarios of homeostatic control mechanisms in steady state as well as severely
      or partially lymphopenic environments.

PMID- 16963129
TI  - Multiple recombinant ELISA for the detection of bovine viral diarrhoea virus
      antibodies in cattle sera.
AB  - The most immunogenic proteins (E0, E2 and NS3) of bovine viral diarrhoea virus
      (BVDV) (NADL strain) were expressed in the baculovirus/insect cells system.
      Recombinant antigens were applied to the design of enzyme immunoabsorbent assays
      (ELISAs) for the detection of specific antibodies in cattle sera. The assays
      developed were shown to be highly sensitive and specific in comparison with the
      viral neutralization test, which is the reference test for the serological
      diagnosis of BVDV. The present results demonstrate the contribution of each
      recombinant antigen to determine clearly the pattern of anti-BVDV antibodies in
      bovine serum samples.

PMID- 16963130
TI  - Increased adamantane resistance in influenza A(H3) viruses in Australia and
      neighbouring countries in 2005.
AB  - The prevention and control of disease caused by seasonal and potential pandemic
      influenza viruses is currently managed by the use influenza vaccines and
      antivirals. The adamantanes (amantadine and rimantadine) were the first
      antivirals licensed for use against influenza A viruses and have been used
      extensively in some countries. Since the early 2000s increased resistance to
      these drugs has been reported especially in the A(H3) viruses. In this study we
      analysed recent human influenza A strains isolated in Australia and regionally
      for evidence of resistance to adamantanes and found evidence of significant
      resistant emerging during 2005.

PMID- 16963131
TI  - Mobilization of PCBs from blubber to blood in northern elephant seals (Mirounga
      angustirostris) during the post-weaning fast.
AB  - Northern elephant seals (Mirounga angustirostris) are characterized by extended
      fasting during which they rely entirely on their own body reserves. During fasts,
      lipids are mobilized from blubber to match the energy requirements of the animal.
      This transfer frees toxic fat-soluble pollutants into the blood circulation,
      which may exert adverse health effects, especially in young and developing
      animals. We investigated the dynamics of mobilization of polychlorinated
      biphenyls (PCBs) from the blubber of northern elephant seal pups during the post
      weaning fast. Longitudinal samples of blubber and serum were collected from free
      ranging animals throughout the fast at Ano Nuevo, California. Blubber biopsies
      were separated into inner and outer layers. The PCB profiles of blubber and serum
      consisted mainly of penta- (PCB-101, -110, -118), hexa- (PCB-138, -153) and hepta
      (PCB-180, -183, -187) chlorobiphenyls, which accounted for almost 90% of the
      total PCB burden. Total PCB concentrations in inner blubber increased
      significantly between early and late fasting (563.6+/-162.0 microg/kg lipids at
      early versus 911.6+/-513.1 microg/kg lipids at late fasting) whereas they
      remained fairly constant in outer blubber (572.6+/-134.8 microg/kg lipids at
      early versus 659.2+/-158.8 microg/kg lipids at late fasting). A corresponding
      rise of PCB concentrations was observed in serum during the second half of the
      fast (3.8+/-1.1 microg/l serum at early versus 7.2+/-0.9 microg/l at late
      fasting). The longitudinal changes in circulating total PCBs could not be
      explained by the changes in serum lipid fractions (cholesterol, phospholipids,
      triacylglycerols and free fatty acids). The increases in total PCB concentrations
      in inner blubber and serum were more pronounced in leaner animals, which suggests
      that they might be more at risk to potential toxic effects.

PMID- 16963132
TI  - Comparative in vitro metabolism of benzo[a]pyrene by recombinant zebrafish CYP1A
      and liver microsomes from beta-naphthoflavone-treated rainbow trout.
AB  - The zebrafish (Danio rerio) is a sensitive non-mammalian model used for studying
      polycyclic aromatic hydrocarbon (PAH)-induced chemical carcinogenesis. The
      susceptibility of zebrafish to PAH-induced carcinogenesis may be related to the
      ability of the zebrafish P450s to bioactivate these procarcinogens. As a part of
      our overall effort to identify the various P450 enzymes that are involved in the
      activation and detoxification of PAHs in zebrafish, therefore, we have examined
      the ability of recombinant zebrafish CYP1A (zCYP1A) expressed in yeast to
      metabolize BaP in vitro. Comparison studies also were conducted with liver
      microsomes from beta-naphthoflavone (BNF)-treated rainbow trout (Oncorhynchus
      mykiss). Results demonstrated that the trout liver microsomes were almost twice
      as active as zCYP1A in oxidizing BaP, with Vmax values of 1.7 and 0.94
      nmol/min/nmol P450 for trout and zebrafish preparations, respectively. Like trout
      CYP1A1, cDNA-expressed zCYP1A was found to oxidize BaP to phenols, quinones and
      diols (BaP-7,8-diol and BaP-9,10-diol) in the presence of exogenous human
      microsomal epoxide hydrolase (hEH). BaP-7,8-diol is the precursor of the ultimate
      carcinogen, BaP-7,8-diol-9,10-epoxide (BaPDE). The ability of zCYP1A to
      bioactivate BaP was confirmed by the formation of DNA adducts when calf thymus
      DNA was added to the incubation mixture. BaP-DNA binding was enhanced by the
      addition of hEH to the incubation mixture. HPLC analysis of the [33P]-postlabeled
      DNA adducts showed the formation of at least four adducts mediated by both zCYP1A
      and trout liver microsomes, and one of these adducts co-migrated with BaPDE-dG in
      HPLC analysis. The addition of hEH to the incubation mixture decreased the
      formation of BaPDE-dG by zCYP1A and by trout liver microsomes while increasing
      the formation of an unidentified DNA adduct in the case of zCYP1A. zCYP1A also
      mediated the binding of BaP to protein, providing further evidence that this
      enzyme is capable of oxidizing BaP to reactive metabolites that bind to
      macromolecules. It thus appears that zCYP1A may play an important role in BaP
      induced carcinogenesis in the zebrafish model by catalyzing the sequential
      formation of the ultimate diol epoxide carcinogenic metabolite of BaP.

PMID- 16963133
TI  - N-terminal positively charged amino acids, but not their exact position, are
      important for apicoplast transit peptide fidelity in Toxoplasma gondii.
AB  - The non-photosynthetic plastid - or apicoplast - of Toxoplasma gondii and other
      apicomplexan parasites is an essential organelle and promising drug target. Most
      apicoplast proteins are encoded in the nucleus and targeted into the organelle
      through the apicoplast's four membranes courtesy of a bipartite N-terminal leader
      sequence comprising of an endomembrane signal peptide followed by a plastid
      transit peptide. Apicoplast transit peptides, like plant plastid transit
      peptides, have no primary consensus, are variable in length and may be
      distinguishable only by a relative depletion of negative charged residues and
      consequent enrichment in basic residues. In this study we examine the role of
      charged residues within an apicoplast transit peptide in T. gondii by point
      mutagenesis. We demonstrate that positive charged residues, combined with the
      absence of negatively charged amino acids, are essential for apicoplast transit
      peptide fidelity, as also observed in P. falciparum. Furthermore, we show that
      positive charge is more important at the transit peptide's N-terminus than its C
      terminus, and that the nature of the positive residue and the exact position of
      the N-terminal positive charge are not important. These results suggest that a
      simple, rule-based prediction for T. gondii transit peptides, similar to that
      successfully implemented for P. falciparum should help to identify apicoplast
      proteins and facilitate the identification of drug targets in this important
      human pathogen.

PMID- 16963134
TI  - Involvement of multiple signaling pathways in PACAP-induced EM66 secretion from
      chromaffin cells.
AB  - Secretoneurin (SN) and EM66 are two highly conserved peptides that derive from
      the processing of secretogranin II (SgII), one of the major constituents of
      chromaffin cell secretory vesicles. It has been shown that PACAP regulates SgII
      gene transcription and SN release in bovine adrenochromaffin cells. The aim of
      the present study was to localize and characterize EM66 in the bovine adrenal
      gland, and to examine the signaling pathways activated by PACAP to regulate the
      secretion of EM66 from cultured chromaffin cells. Double immunohistochemical
      labeling showed an intense EM66-immunoreactive (EM66-IR) signal in TH-positive
      medullary chromaffin cells of the adrenal gland. HPLC analysis combined with RIA
      detection revealed, in adrenal medulla extracts and cultured chromaffin cell
      media, the presence of a major EM66-IR peak co-eluting with the recombinant
      peptide. PACAP dose-dependently stimulated EM66 release from chromaffin cells
      (ED(50)=4.8 nM). The effect of PACAP on EM66 secretion was observed after 6 h of
      treatment and increased to reach a 2.6-fold stimulation at 48 h. The nonselective
      calcium channel blocker NiCl(2), the cytosolic calcium chelator BAPTA-AM and the
      L-type calcium channel blocker nimodipine significantly inhibited the stimulatory
      effect of PACAP on EM66 release. The secretory response to PACAP was also
      significantly lowered by the protein kinase A inhibitor H89 and by the protein
      kinase C inhibitor chelerythrine. Concomitant administration of chelerythrine,
      H89, NiCl(2) and BAPTA totally abolished PACAP-stimulated EM66 secretion. The
      MAPK inhibitors U0126 and SB203580 respectively decreased by 63% and 72% PACAP
      evoked EM66 release. These results indicate that, in bovine adrenal medulla, SgII
      is processed to generate the EM66 peptide and that PACAP activates multiple
      signaling pathways to regulate EM66 release from chromaffin cells, suggesting
      that EM66 may act downstream of the trans-synaptic stimulation of the adrenal
      medulla by neurocrine factors.

PMID- 16963135
TI  - Ontogeny of PACAP receptors in the human cerebellum: perspectives of therapeutic
      applications.
AB  - It is now well established that pituitary adenylate cyclase-activating
      polypeptide (PACAP) exerts anti-apoptotic and pro-differentiating actions during
      development of the rodent cerebellum. Cell signaling involved in the neurotrophic
      effects of PACAP has been precisely investigated. In particular, PACAP is a
      potent inhibitor of the mitochondrial apoptotic pathway through an ERK- and PKA
      dependent mechanism. However, transposition of the neurodevelopmental activities
      of PACAP to the human cerebellum remains speculative, essentially because of the
      lack of data concerning the PACAP-ergic system. The present review is based on
      recent results that provide the first molecular, pharmacological and anatomical
      characterizations of PACAP receptors in the developing human cerebellum. It is
      now clearly established that the distribution pattern of PAC1-R and VPAC1-R mRNA
      in the human cerebellum is very similar to that already described in rodents.
      [(125)I]PACAP27 binding sites are closely associated with germinative
      neuroepithelia in fetal stages and with mature granule cells in infants and
      adults. Pharmacological characterization revealed that, in fetuses, PACAP binding
      sites exhibit a PAC1-R profile while, in adult patients, they correspond to a
      heterogeneous population of PAC1-R and VPAC(1/2)-R. Altogether, these data
      provide the first evidence that PACAP may exert neurodevelopmental functions in
      the human cerebellum.

PMID- 16963136
TI  - An ITIM-like motif within the CCK2 receptor sequence required for interaction
      with SHP-2 and the activation of the AKT pathway.
AB  - SHP-2 is a tyrosine phosphatase which functions as a positive regulator
      downstream of RTKs, activating growth-stimulatory signalling pathways. To date,
      very few G protein-coupled receptors (GPCRs) have been shown to be connected to
      SHP-2 and very little is known about the positive role of SHP-2 in GPCR
      signalling. The CCK2 receptor (CCK2R), a GPCR, is now recognized to mediate
      mitogenic effects of gastrin on gastrointestinal cells. In the present study, we
      demonstrate the role of SHP-2 in the activation of the AKT pathway by the CCK2R
      in COS-7 cells transfected with the CCK2R and in a pancreatic cancer cell line
      expressing the endogenous receptor. Using surface plasmon resonance analysis, we
      identified a highly conserved ITIM motif, containing the tyrosine residue 438,
      located in the C-terminal intracellular tail of the CCK2R which directly
      interacts with the SHP-2 SH2 domains. The interaction was confirmed by pull down
      assays and co-immunoprecipitation of the receptor with SHP-2. This interaction
      was transiently increased following gastrin stimulation of the CCK2R and
      correlated with the tyrosine phosphorylation of SHP-2. Mutational analysis of the
      key ITIM residue 438 confirmed that the CCK2R ITIM sequence is required for
      interaction with SHP-2 and the activation of the AKT pathway.

PMID- 16963138
TI  - Inequality and mortality: long-run evidence from a panel of countries.
AB  - We investigate whether changes in economic inequality affect mortality in rich
      countries. To answer this question we use a new source of data on income
      inequality: tax data on the share of pretax income going to the richest 10% of
      the population in Australia, Canada, France, Germany, Ireland, the Netherlands,
      New Zealand, Spain, Sweden, Switzerland, the UK, and the US between 1903 and
      2003. Although this measure is not a good proxy for inequality within the bottom
      half of the income distribution, it is a good proxy for changes in the top half
      of the distribution and for the Gini coefficient. In the absence of country and
      year fixed effects, the income share of the top decile is negatively related to
      life expectancy and positively related to infant mortality. However, in our
      preferred fixed-effects specification these relationships are weak, statistically
      insignificant, and likely to change their sign. Nor do our data suggest that
      changes in the income share of the richest 10% affect homicide or suicide rates.

PMID- 16963137
TI  - Effects of rivastigmine on actigraphically monitored motor activity in severe
      agitation related to Alzheimer's disease: a placebo-controlled pilot study.
AB  - Acetylcholinesterase inhibitors (AChEIs) are effective in the treatment of
      cognitive symptoms in Alzheimer's disease (AD). Because the behavioral and
      psychological symptoms of dementia (BPSD) have also been attributed to central
      cholinergic deficits, we examined whether the AChEI rivastigmine can reduce motor
      activity as measured in a rater-independent manner by wrist actigraphy in
      agitated AD patients. A total of 20 consecutive AD inpatients (13 females, 7
      males, 80.4+/-9.1 years, S.D.) were included from our geriatric psychiatry unit,
      all of whom were exhibiting agitated behavior not attributable to delirium.
      Patients were assigned randomly and in a single-blinded fashion to rivastigmine
      3mg or placebo for 14 days. Motor activity levels were monitored using an
      actigraph worn continuously on the wrist of the non-dominant hand. At the
      beginning and end of the study, patients were assessed using the Neuropsychiatric
      Inventory (NPI) and Nurses' Observation Scale for Geriatric Patients (NOSGER).
      Patients in the rivastigmine group exhibited less agitation than placebo
      recipients on the NPI-agitation subscale, but not on NOSGER. Actigraphic
      measurements showed a tendency towards reduced motor activity in the rivastigmine
      group. Because rivastigmine usually exerts its main effects after a longer period
      of time, the short-term effects seen in our study justify further controlled
      clinical trials examining the use of rivastigmine in BPSD by means of actigraphy.

PMID- 16963139
TI  - Novel multiplex PCR approaches for the simultaneous detection of human pathogens:
      Escherichia coli 0157:H7 and Listeria monocytogenes.
AB  - Escherichia coli 0157:H7 and Listeria monocytogenes are the two most important
      food-borne human pathogens. To develop a single, rapid and sensitive PCR based
      test for simultaneous detection of both the organisms, fliCh7 and iap gene
      specific primers were used respectively for E. coli 0157:H7 and L. monocytogenes.
      Initially, with equal quantities of purified genomic DNAs of these organisms a
      multiplex PCR reaction was standardized to yield uniform amplification of both
      targets. Although, this assay detected E. coli 0157:H7 with high sensitivity, it
      failed to pick up L. monocytogenes after several hours of enrichment in broth
      medium initially spiked with equal numbers of live cells. This was found to be
      due to unequal growth of these organisms leading to disparity in the amount of
      template DNAs represented in the DNA preparation applied for conventional
      multiplex PCR amplification. To circumvent this, we have developed a modified
      method of enrichment and harvesting leading to highly sensitive and rapid single
      reaction PCR detection of both pathogens. We have also successfully developed two
      novel multiplex PCR formats for the generation of uniform PCR signals. Some of
      these methods might find broader application for the simultaneous detection of
      different combinations of multiple pathogens.

PMID- 16963140
TI  - Rehabilitation of adaptive immunity and regeneration of beta cells.
AB  - Type 1 Diabetes (T1D) is an autoimmune disease resulting from the destruction of
      pancreatic insulin-producing beta cells that most frequently occurs in
      genetically predisposed children. Recent observations illustrating the
      regenerative capability of the endocrine pancreas in addition to advances in stem
      cell and gene therapy technologies enable the exploration of alternatives to
      allogeneic islet transplantation. Living-cell-mediated approaches can abrogate
      autoimmunity and the consequent destruction of beta cells without the need for
      immunosuppressive drugs. Such approaches can be used as a foundation for new
      protocols that more easily translate to the clinical setting. The twin goals of
      controlling autoimmune disease and promoting stable regeneration of insulin
      producing beta cells should be considered the cornerstones of the successful
      development of a cure for this chronic disease.

PMID- 16963141
TI  - Identification of novel enzymes with different hydrolytic activities by
      metagenome expression cloning.
AB  - Metagenome cloning has become a powerful tool to exploit the biocatalytic
      potential of microbial communities for the discovery of novel biocatalysts. In a
      novel variant of direct expression cloning, metagenomic DNA was isolated from
      compost by a modified direct lysis method, purified by size exclusion
      chromatography and cloned into an expression vector allowing bidirectional
      transcription. Transformation of Escherichia coli DH5alpha resulted in a
      metagenomic expression library with an average insert size of 3.2 kb. To estimate
      the functional diversity of the constructed library, it was screened by different
      approaches based on functional heterologous expression. A large number of active
      clones were identified, including lipolytic enzymes, amylases, phosphatases and
      dioxygenases. Molecular analysis of one important class of industrial
      biocatalysts, the lipolytic enzymes, confirmed the novelty and dissimilarity of
      all recovered genes, which exhibited only limited similarity to known enzymes.
      Equally, the novelty of another three genes encoding phosphatase or dioxygenase
      activity, respectively, was shown. These results demonstrate the suitability of
      this direct cloning approach, which comprised a dual-orientation expression
      vector and a simple one-step DNA purification method, for the efficient discovery
      of numerous active novel clones. By this means it provides an efficient way for
      the rapid generation of large libraries of hitherto unknown enzyme candidates
      which could be screened for different specific target reactions.

PMID- 16963143
TI  - Characterizing the structure/function parameter space of hydrocarbon-conjugated
      branched polyethylenimine for DNA delivery in vitro.
AB  - Polyethylenimine is a popular DNA transfection reagent, and many approaches have
      been explored to further enhance its transfection efficiency. Substitution of
      branched polyethylenimine's primary amine groups is an attractive approach
      because it is amenable to a variety of chemistries and is also implicated as a
      primary factor in its cytotoxicity. The purpose of this work was to serially
      substitute saturated hydrocarbons to branched polyethylenimine and determine what
      structure/function relationships exist between the hydrocarbon length and its
      degree of substitution, relative to transfection efficiency in multiple cell
      lines. Specifically, acetate, butanoate and hexanoate were conjugated to branched
      polyethylenimine (M(w) = 25,000) using an aqueous condensation protocol.
      Transfections were performed in culture using HeLa, NIH/3T3 and Clone 9 cell
      lines. Biophysical characteristics of the polyelectrolyte complexes were also
      measured (hydrodynamic diameter, relative binding affinity) and correlated to
      transfection efficiency. The results show that substitution of the primary amines
      generally increases transfection efficiency relative to unconjugated
      polyethylenimine, but increasing the degree of substitution beyond approximately
      25 mol% generally decreases transfection efficiency from the optimum.
      Additionally, increasing hydrocarbon length generally decreased transfection
      efficiency. There was little correlation between particle size and binding
      efficiency to transfection efficiency.

PMID- 16963142
TI  - The chemokine receptor homologue encoded by US27 of human cytomegalovirus is
      heavily glycosylated and is present in infected human foreskin fibroblasts and
      enveloped virus particles.
AB  - Human cytomegalovirus (HCMV), a member of the beta-herpesvirus family, encodes
      four homologues of cellular G protein-coupled receptors (GPCRs). One of these,
      the protein product of HCMV open reading frame (ORF) UL33, has been identified in
      HCMV-infected cells and virus particles and shown to be heat-aggregatable and N
      glycosylated. Another, the product of ORF US28, has been functionally
      characterized as a beta-chemokine receptor. Here we report the use of RT-PCR,
      coupled in vitro transcription-translation, immunoprecipitation, and Western
      immunoassays to (i) show that RNA from the open reading frame US27 appears
      predominantly during the late phase of replication; (ii) identify the protein
      encoded by HCMV US27 in infected cells and enveloped virus particles; (iii)
      demonstrate that the US27-encoded protein is heterogeneously N-glycosylated and
      resolves as two species following treatment with peptide N-glycosidase F; and
      (iv) show that both the recombinant and deglycoylated infected cell US27 protein
      aggregate when heated in the presence of SDS prior to electrophoresis in
      polyacrylamide gels, a property which is abrogated with the addition of urea to
      sample buffer.

PMID- 16963144
TI  - Intracellular drug delivery by sulfatide-mediated liposomes to gliomas.
AB  - We described here a liposomal carrier system in which the targeting ligand was
      sulfatide, a glycosphingolipid known to bind several extracellular matrix (ECM)
      glycoproteins whose expression was highly up-regulated in many tumors. In vitro
      experiments with human glioma cell lines demonstrated that robust intracellular
      uptake of the liposomes depended specifically on the presence of sulfatide as the
      key liposomal component. Significant amount of the liposomes remained largely
      intact in the cytoplasm for hours following their internalization. When
      anticancer drug doxorubicin (DOX) was encapsulated in such liposomes, most of the
      drug was preferably delivered into the cell nuclei to exert its cytotoxicity. Use
      of this drug delivery system to deliver DOX for treatment of tumor-bearing nude
      mice displayed much improved therapeutic effects over the free drug or the drug
      carried by polyethylene glycol (PEG)-grafted liposomes. Our results demonstrate a
      close link between effective intracellular uptake of the drug delivery system and
      its therapeutic outcome. Moreover, the sulfatide-containing liposomes (SCL) may
      represent an interesting ligand-targeted drug carrier for a wide spectrum of
      cancers in which sulfatide-binding ECM glycoproteins are expressed.

PMID- 16963145
TI  - Stability of poly(D,L-lactide-co-glycolide) and leuprolide acetate in in-situ
      forming drug delivery systems.
AB  - In-situ forming drug delivery systems are prepared by dissolving a drug and a
      biodegradable polymer (poly(D,L-lactide-co-glycolide), PLGA) in a biocompatible
      organic solvent (In-situ implant, ISI) or further emulsified into an external
      phase (oil or aqueous solution), resulting in oil-in-oil or oil-in-water
      emulsions (In-situ forming microparticles, ISM). The chemical stability of PLGA
      and the drug is a major concern. In this study, the stability of PLGA and
      leuprolide acetate in the in-situ forming systems and lyophilized sponges was
      investigated. The degradation of PLGA increased with increasing storage
      temperature and water content in the biocompatible solvents. A faster degradation
      occurred in polar protic solvents (2-pyrrolidone, PEG 400, triethyl citrate) than
      in polar aprotic solvents (N-methyl-2-pyrrolidone, DMSO, triacetin, ethyl
      acetate). The presence of leuprolide acetate significantly accelerated PLGA
      degradation, especially in solution state. PLGA was stable in oily suspensions at
      4 degrees C and degraded only slightly faster than solid powder at 25 degrees C.
      No interaction between the oils and the PLGA was observed as indicated by an
      unchanged T(g) of approx. 47 degrees C. PLGA underwent a slight degradation at 4
      degrees C after 150 days in water and saturated sodium chloride solution. The
      degradation was slower in saturated sodium chloride solution than in water at 25
      degrees C. Residual acetic acid in lyophilized sponges facilitated the PLGA
      degradation in contrast to dioxane. Leuprolide acetate did not affect the PLGA
      stability negatively. However, lidocaine significantly enhanced the polymer
      degradation in the sponges. Finally, leuprolide acetate was chemically stable in
      the sponges, the oils and the polymer solutions in suspension state, but unstable
      (aggregation) when dissolved in the polymer solutions and stored at 25 degrees C
      and 40 degrees C.

PMID- 16963146
TI  - Hyperhomocysteinemia induces insulin resistance in male Sprague-Dawley rats.
AB  - Association between elevated plasma homocysteine levels and insulin resistance
      has been reported, however, whether hyperhomocysteinemia induces insulin
      resistance or it is actually hyperinsulinemia that causes elevated plasma
      homocysteine levels, the direction of causality in this association is not still
      clear. In this study, we examined the hypothesis that hyperhomocysteinemia may
      cause hyperinsulinemia leading to insulin resistance in rats. Plasma glucose,
      insulin and total homocysteine concentrations were determined in two groups of
      male Sprague-Dawley rats, a test group that administered with homocysteine and a
      control group with no homocysteine in daily drinking water before and after 50
      days. Oral glucose tolerance tests were also performed in control and test groups
      before and after 50 days. Mean fasting plasma insulin level was significantly
      higher (42.5+/-20.4 mU/L versus 23.2+/-5.9 mU/L, p=0.01), whereas mean glucose:
      insulin ratio was significantly lower in test rats than in control rats (0.12+/
      0.07 versus 0.17+/-0.05, p=0.04) after 50 days. In addition, mean homeostasis
      assessment insulin resistance index was significantly higher in test rats than in
      control rats (7.5+/-3.5 versus 4.0+/-1.6, p=0.02) after 50 days. The mean plasma
      glucose level was not significantly different (4.1+/-1.1 mmol/L versus 3.9+/-0.8
      mmol/L, p=0.57) between controls and test rats, however, the results from oral
      glucose tolerance tests showed the development of insulin resistance in test rats
      after 50 days administration of homocysteine. Results from this in vivo study
      suggest that homocysteine can cause insulin resistance and this relationship may
      need to be considered when evaluating the role of plasma homocysteine as a risk
      factor in patients with obesity and type II diabetes.

PMID- 16963147
TI  - Seasonal variation in the diagnosis of type 1 diabetes in south-east Sweden.
AB  - With the aim to survey the seasonal pattern of diagnosis of type 1 diabetes we
      included all 1903 children <16 years of age and who had been diagnosed with type
      1 diabetes between 1977 and 2001 in the south-east of Sweden. To investigate the
      seasonal pattern a mixture of two cosine functions was included in a logistic
      regression model. There was a clear seasonal variation over the years (p<0.001).
      Children in the oldest age group (11-15 years) showed the most obvious seasonal
      variation (p<0.001). Children with a short duration of symptoms had about the
      same seasonal variation as children with a long duration. Both children with and
      without an infection 3 months prior to diagnosis showed significant seasonal
      variation (p<0.001) although the seasonal pattern differed between the two groups
      (p<0.001). As the incidence of diabetes increased during the 25 years the study
      period was divided into periods of 5 years and it was only during the two last
      periods that significant seasonal variation occurred. There is a clear seasonal
      variation in diagnosis of type 1 diagnosis in children and the results suggest
      that children with a less aggressive disease process at diagnosis were most
      responsible for this variation. Children with and without prior infection showed
      a different seasonal pattern.

PMID- 16963148
TI  - Methicillin-resistant Staphylococcus aureus (MRSA) isolation from diabetic foot
      ulcers correlates with nasal MRSA carriage.
AB  - Methicillin-resistant Staphylococcus aureus is increasingly isolated from
      diabetic foot ulcers, and may be associated with an adverse prognosis. We have
      explored the relationship between MRSA isolation from foot ulcers and nasal MRSA
      carriage. Over a 12 month period, 65 consecutively attending patients with
      diabetic foot ulceration were recruited. Demographic information was collected,
      and the ulcer and nose swabbed bacteriologically using standard techniques. The
      patients were mean age 61 year, diabetes duration 14 year, and HbA1c 8.5%. There
      were 61% male and 85% with type 2 diabetes. Ulcers were neuropathic in 55%,
      ischaemic in 14% and neuroischaemic in 31%. MRSA was isolated from 12 (19%)
      ulcers, and 11 (17%) had nasal carriage. Of the MRSA positive ulcer patients 7/12
      (58%) had nasal MRSA carriage, compared with 4/53 (8%) with MRSA negative ulcers
      (p<0.0003). We conclude that nasal MRSA carriage in diabetic patients is a
      significant risk factor for foot ulcer MRSA infection.

PMID- 16963149
TI  - Possible relevance of alpha lipoic acid contained in a health supplement in a
      case of insulin autoimmune syndrome.
AB  - The insulin autoimmune syndrome is characterized as producing polyclonal or
      monoclonal anti-insulin autoantibodies in a patient with no previous history of
      exposure to exogenous insulin. The patient is 44-year-old Japanese woman and she
      had symptoms of hypoglycaemia without exposure to exogenous insulin. The patient
      was considered to have IAS because high titre of anti-insulin autoantibodies (96
      98%: bound/total) were found in her serum. Her HLA DR beta1 DNA sequences
      analysis revealed that she has the DRB1(*)0406 and DRB1(*)0901. Our patient have
      been taken alpha lipoic acid (ALA) before onset. SH group compounds are known to
      play an important role in the pathogenesis of IAS, and ALA contains SH. From
      these data, we propose the possibility of the correlation between pathogenesis of
      IAS and ALA, and it will be important to pay attention for ALA as a cause of
      hypoglycemia in such cases.

PMID- 16963150
TI  - Diabetes associated with a low serum uric acid level in a general Chinese
      population.
AB  - OBJECTIVE: Serum uric acid (UA) is reported as an important marker of
      hypertension, coronary heart disease, and diabetes; diabetic subjects have low UA
      levels. The relationship between UA and fasting plasma glucose (FPG) and 2-h
      plasma glucose concentrations in non-diabetic subjects as well as in diabetic
      subjects in general population is not well known. This was investigated in a
      general Chinese population. METHODS: A stratified, random cluster sampling method
      was performed to select a representative sample of general population aged 20-74
      years in Qingdao in 2002. A total of 1288 men and 2344 women participated in the
      survey. The mean UA concentration was calculated for small glucose intervals and
      the trend was tested using general linear model. RESULTS: The mean concentrations
      of UA were 381, 393, 371, and 345 micromol/l in men with FPG of <6.1, 6.1-6.9, >
      or =7.0 mmol/l (newly diagnosed diabetes), and in those with prior history of
      diabetes. They were 308, 322, 301, and 293 micromol/l, respectively, in women.
      The UA levels declined with increasing FPG levels in individuals with newly
      diagnosed diabetes, with standardized coefficient of -0.26 in men and -0.20 in
      women, after multivariate adjustment for age, body mass index, triglycerides, and
      cardiovascular disease history. The relationship between 2-h glucose and UA was
      not as clear as that for FPG. CONCLUSION: Serum UA levels tended to increase with
      increasing FPG levels in non-diabetic individuals, but decrease in diabetic
      individuals.

PMID- 16963151
TI  - Increased intima-media thickness of the carotid artery in Japanese female type 2
      diabetic patients with 'midband lipoprotein'.
AB  - Among a number of different lipoprotein abnormalities, 'midband lipoprotein'
      migrating at a position between LDL and VLDL on polyacrylamide gel
      electrophoresis (PAGE), is an atherogenic lipoprotein and intima-media thickness
      (IMT) of the carotid artery is a useful marker of atherosclerotic diseases. The
      present study evaluated relationships between the presence of 'midband
      lipoprotein' and carotid IMT in subjects with type 2 diabetes. The average IMT of
      the carotid artery was determined from the means of maximal thicknesses of both
      left and right common carotid arteries, carotid bulb, and internal carotid artery
      using ultrasound B mode imaging in 118 Japanese patients (72 men, 46 women) and
      43 healthy controls. Multivariate regression analyses indicated that the duration
      of diabetes and presence of 'midband lipoprotein' were independent determinants
      of carotid artery IMT in 46 female subjects with diabetes, and these subjects
      were then subclassified into midband-positive (n=24) and midband-negative (n=22)
      groups. IMT of the carotid artery was significantly different between midband
      positive (0.98+/-0.32mm) and midband-negative (0.79+/-0.17mm) groups (P=0.02).
      These findings suggest that 'midband lipoprotein' is a possible risk factor for
      IMT of the carotid artery in Japanese female type 2 diabetic patients.

PMID- 16963152
TI  - Type 2 diabetes and hearing loss in personnel of the Self-Defense Forces.
AB  - The association of type 2 diabetes with hearing loss was evaluated in middle-aged
      male personnel of the Self-Defense Forces (SDFs). Hearing loss was defined as the
      pure-tone average (PTA) of the thresholds frequency at 0.5, 1, 2, and 4 kHz
      greater than 25 dB hearing levels (HL) in the worse ear. Diabetes status was
      determined by self-report of physician-diagnosed diabetes or by oral glucose
      tolerance test (OGTT). Of 699 subjects studied (age 52.9+/-1.0 years), 103
      subjects were classified as having type 2 diabetes. Fasting plasma glucose of
      diabetic subjects was 120+/-19 mg/dl. Hearing loss levels were (worse) higher
      among diabetic subjects compared with subjects with normal glucose tolerance
      (NGT) (30.7+/-13.0 dB versus 27.4+/-12.3 dB, P=0.014). Hearing loss was more
      prevalent among diabetic subjects than among subjects with normal glucose
      tolerance (60.2% versus 45.2%, P=0.006). The odds ratio (OR) of type 2 diabetes
      for the presence of hearing loss was 1.87 (95% confidence interval 1.20-2.91,
      P=0.006) in a logistic regression analysis adjusted for age, rank, cigarette
      smoking and ethanol consumption. These results suggest that type 2 diabetes is
      associated with hearing loss independently of lifestyle factors in middle-aged
      men.

PMID- 16963153
TI  - GCK and HNF1alpha mutations and polymorphisms in Polish women with gestational
      diabetes.

PMID- 16963154
TI  - SPATCLUS: an R package for arbitrarily shaped multiple spatial cluster detection
      for case event data.
AB  - This paper describes an R package, named SPATCLUS that implements a method
      recently proposed for spatial cluster detection of case event data. This method
      is based on a data transformation. This transformation is achieved by the
      definition of a trajectory, which allows to attribute to each point a selection
      order and the distance to its nearest neighbour. The nearest point is searched
      among the points which have not yet been selected in the trajectory. Due to the
      trajectory effects, the distance is weighted by the expected distance under the
      uniform distribution hypothesis. Potential clusters are located by using multiple
      structural change models and a dynamic programming algorithm. The double maximum
      test allows to select the best model. The significativity of potential clusters
      is determined by Monte Carlo simulations. This method makes it possible the
      detection of multiple clusters of any shape.

PMID- 16963155
TI  - Biodegradation of hydrocarbons vapors: Comparison of laboratory studies and field
      investigations in the vadose zone at the emplaced fuel source experiment, Airbase
      Vaerlose, Denmark.
AB  - The natural attenuation of volatile organic compounds (VOCs) in the unsaturated
      zone can only be predicted when information about microbial biodegradation rates
      and kinetics are known. This study aimed at determining first-order rate
      coefficients for the aerobic biodegradation of 13 volatile petroleum hydrocarbons
      which were artificially emplaced as a liquid mixture during a field experiment in
      an unsaturated sandy soil. Apparent first-order biodegradation rate coefficients
      were estimated by comparing the spatial evolution of the resulting vapor plumes
      to an analytical reactive transport model. Two independent reactive numerical
      model approaches have been used to simulate the diffusive migration of VOC vapors
      and to estimate degradation rate coefficients. Supplementary laboratory column
      and microcosm experiments were performed with the sandy soil at room temperature
      under aerobic conditions. First-order kinetics adequately matched the lab column
      profiles for most of the compounds. Consistent compound-specific apparent first
      order rate coefficients were obtained by the three models and the lab column
      experiment, except for benzene. Laboratory microcosm experiments lacked of
      sensitivity for slowly degrading compounds and underestimated degradation rates
      by up to a factor of 5. Addition of NH3 vapor was shown to increase the
      degradation rates for some VOCs in the laboratory microcosms. All field models
      suggested a significantly higher degradation rate for benzene than the rates
      measured in the lab, suggesting that the field microbial community was superior
      in developing benzene degrading activity.

PMID- 16963156
TI  - WCS120 protein family and proteins soluble upon boiling in cold-acclimated winter
      wheat.
AB  - The amount of proteins soluble upon boiling (especially WCS120 proteins) and the
      ability to develop frost tolerance (FT) after cold acclimation was studied in two
      frost-tolerant winter wheat cultivars, Mironovskaya 808 and Bezostaya 1. Protein
      gel blot analysis, mass spectrometry (MS) and image analysis of two-dimensional
      gel electrophoresis (2-DE) gels were used to identify and/or quantify the
      differences in protein patterns before (non-acclimated, NA) and after 3 weeks of
      cold acclimation (CA) of the wheats, when FT increased from -4 degrees C (lethal
      temperature (LT(50)), for both cultivars) to -18.6 degrees C in Bezostaya 1 and 
      20.8 degrees C in Mironovskaya 808. Only WCS120 protein was visible in NA leaves
      while all five WCS120 proteins were induced in the CA leaves. Mironovskaya 808
      had higher accumulation of three members of WCS120 proteins (WCS120, WCS66 and
      WCS40) than Bezostaya 1. MS analysis of total sample of proteins soluble upon
      boiling showed seven COR proteins in the CA samples and only three COR proteins
      in the NA samples of cultivar Mironovskaya 808 (MIR). In conclusion, the level of
      the accumulation of WCS120, WCS66 and WCS40 distinguished our two frost-tolerant
      winter wheat cultivars. Moreover, the differences of CA and NA samples of the MIR
      were shown by liquid chromatography (LC)-tandem mass spectrometry (MS/MS).

PMID- 16963157
TI  - Dmt-Tic-NH-CH2-Bid (UFP-502), a potent DOP receptor agonist: in vitro and in vivo
      studies.
AB  - Knockout and pharmacological studies demonstrated that the activation of delta
      opioid peptide (DOP) receptors produces antidepressant-like effects in rodents.
      Here we report the results obtained with the novel DOP ligand H-Dmt-Tic-NH-CH(2)
      Bid (UFP-502). UFP-502 bound with high affinity (pK(i) 9.43) to recombinant DOP
      receptors displaying moderate selectivity over MOP and KOP. In CHO(hDOP)
      [(35)S]GTPgammaS binding and mouse vas deferens experiments, UFP-502 behaved as a
      potent (pEC(50) 10.09 and 10.70, respectively) full agonist. In these
      preparations, naloxone, naltrindole and N,N(CH(3))(2)Dmt-Tic-OH showed similar
      pA(2) values against UFP-502 and DPDPE and the same rank order of potency. In
      vivo in mice, UFP-502 mimicked DPDPE actions, producing a significant reduction
      of immobility time after intracerebroventricular administration in the forced
      swimming test and a clear antinociceptive effect after intrathecal injection in
      the tail withdrawal assay. However, while the effects of DPDPE were fully
      prevented by naltrindole those evoked by UFP-502 were unaffected (tail withdrawal
      assay) or only partially reversed (forced swimming test). In conclusion, UFP-502
      represents a novel and useful chemical template for the design of selective
      agonists for the DOP receptor.

PMID- 16963158
TI  - Effects of oral preload, CCK or bombesin administration on short term food intake
      of melanocortin 4-receptor knockout (MC4RKO) mice.
AB  - We investigated whether either heterozygous (HET) or homozygous (knockout, KO)
      disruption of the melanocortin type 4 receptor (MC4R) gene alters post ingestive
      responsiveness of mice. Specifically, we tested the hypothesis that hyperphagia
      in MC4RKO mice might be due to a deficit in processes that sustain intermeal
      intervals (satiety) and/or processes that terminate ongoing episodes of eating
      (satiation). To test satiety, mice drank an oral preload and then we monitored
      intake of a subsequent liquid diet test meal. To test satiation, we examined the
      effect of exogenous administration of cholecystokinin (CCK) and bombesin (BN) on
      the size of a liquid diet meal. Experiment 1 was comprised of two studies. In the
      first, we determined that the intake of all three genotypes following fasts of
      either 6, 12, or 24h were comparable, and so chose 12h deprivation for the
      subsequent studies. In the second, 12h fasted mice were allowed to consume a
      fixed preload, approximately 50% of their expected mean intake and, following
      delays of either 30 or 60 min, were allowed to consume to satiation. Compared
      with no preload, the preload significantly reduced meal size comparably in all
      three genotypes. The reduction in intake was greater when the test meal was
      presented 30 compared with 60 min after the preload, again with no genotype
      differences in this decay of satiety. In experiment 2, we administered either CCK
      or BN and examined suppression of meal size after a 12h fast. Mice were tested
      repeatedly with CCK-8 (2, 6, or 18 microg/kg ip) or BN (2, 4 or 8 microg/kg ip)
      with vehicle injection days intervening. The 30 min intakes of HET and KO mice
      were suppressed more than those of WT following either CCK or BN. These
      experiments suggest that diminished responsiveness to nutrients or gut satiety
      hormones is not responsible for hyperphagia in MC4RKO mice.

PMID- 16963159
TI  - Isolation and biochemical characterization of peptides presenting antimicrobial
      activity from the skin of Phyllomedusa hypochondrialis.
AB  - Amphibian antimicrobial peptides have been known for many decades and several of
      them have been isolated from anuran species. Dermaseptins are among the most
      studied antimicrobial peptides and are found in the skin secretion of tree frogs
      from the Phyllomedusinae subfamily. These peptides exert a lytic action on
      bacteria, protozoa, yeast, and filamentous fungi at micromolar concentrations,
      but unlike polylysines, present little hemolytic activity. In this work, two
      antimicrobial peptides were isolated from the crude skin secretion of
      Phyllomedusa hypochondrialis and tested against Gram-positive and Gram-negative
      bacteria, presenting no hemolytic activity at the tested concentrations. One of
      them was identified with the recently reported peptide PS-7 belonging to the
      phylloseptin family, and another was a novel peptide, named DPh-1, which was
      fully purified, sequenced by 'de novo' mass spectrometry and grouped into
      Dermaseptins (DPh-1).

PMID- 16963160
TI  - The antimicrobial peptide cathelicidin interacts with airway mucus.
AB  - Antimicrobial peptides (AMPs) and mucins are components of airway secretions and
      both contribute to the innate host defense system. At neutral pH, AMPs are
      positively charged, mucins negatively. It was the aim of the study to test
      whether these opposite charges result in interactions between AMPs and mucins. We
      measured binding of mucins isolated from porcine gastric mucosa to the
      cathelicidin LL-37 coated to multiwell plates and found that LL-37
      electrostatically interacts with mucins. Circular dichroism spectra of the
      peptide revealed the induction of alpha-helical conformation by mucins. Addition
      of mucins to solutions of LL-37 significantly decreased the antimicrobial
      activity of the peptide against Pseudomonas aeruginosa and Streptococcus
      pneumoniae. We then tested whether LL-37 is bound to mucins in airway secretions
      from human subjects and found that a significant proportion of the peptide and
      its propeptide are bound to high molecular weight components. Together these data
      show that cationic AMPs interact with anionic mucins in airway secretions.
      Functions of AMPs are modulated by this interaction.

PMID- 16963161
TI  - Methylene blue prevents methylmalonate-induced seizures and oxidative damage in
      rat striatum.
AB  - Methylene blue (MB) is a thiazine dye with cationic and lipophilic properties
      that acts as an electron transfer mediator in the mitochondria. Due to this
      metabolic improving activity and free radicals scavenging effects, MB has been
      used in the treatment of methemoglobinemia and ifosfamide-induced encephalopathy.
      Considering that methylmalonic acidemia consists of a group of inherited
      metabolic disorders biochemically characterized by impaired mitochondrial
      oxidative metabolism and reactive species production, we decided to investigate
      whether MB, protects against the behavioral and neurochemical alterations
      elicited by the intrastriatal injection of methylmalonate (MMA). In the present
      study we showed that intrastriatal injection of MB (0.015-1.5nmol/0.5microl)
      protected against seizures (evidenced by electrographic recording), protein
      carbonylation and Na(+),K(+)-ATPase inhibition ex vivo induced by MMA
      (4.5micromol/1.5microl). Furthermore, we investigated whether convulsions
      elicited by intrastriatal MMA administration are accompanied by striatal protein
      carbonyl content increase and changes in Na(+),K(+)-ATPase activity in rat
      striatum. The effect of MB (0.015-1.5nmol/0.5microl) and MMA
      (4.5micromol/0.5microl) on striatal NO(x) (NO(2) plus NO(3)) content was also
      evaluated. Statistical analysis revealed that the MMA-induced NO(x) content
      increase was attenuated by intrastriatal injection of MB and the duration of
      convulsive episodes correlated with Na(+),K(+)-ATPase inhibition, but not with
      MMA-induced total protein carbonylation. In view of that MB decreases MMA-induced
      neurotoxicity assessed by behavioral and neurochemical parameters, the authors
      suggest that MB may be of value to attenuate neurological deficits of
      methylmalonic acidemic patients.

PMID- 16963162
TI  - Differential activation of protein kinase C isoforms following chemical ischemia
      in rat cerebral cortex slices.
AB  - The aim of the current study was to characterize the effects of chemical ischemia
      and reperfusion at the transductional level in the brain. Protein kinase C
      isoforms (alpha, beta(1), beta(2), gamma, delta and epsilon) total levels and
      their distribution in the particulate and cytosolic compartments were
      investigated in superfused rat cerebral cortex slices: (i) under control
      conditions; (ii) immediately after a 5-min treatment with 10mM NaN(3), combined
      with 2mM 2-deoxyglucose (chemical ischemia); (iii) 1h after chemical ischemia
      (reperfusion). In control samples, all the PKC isoforms were detected;
      immediately after chemical ischemia, PKC beta(1), delta and epsilon isoforms
      total levels (cytosol+particulate) were increased by 2.9, 2.7 and 9.9 times,
      respectively, while alpha isoform was slightly reduced and gamma isoform was no
      longer detectable. After reperfusion, the changes displayed by alpha, beta(1),
      gamma, delta and epsilon were maintained and even potentiated, moreover, an
      increase in beta(2) (by 41+/-12%) total levels became significant. Chemical
      ischemia-induced a significant translocation to the particulate compartment of
      PKC alpha isoform, which following reperfusion was found only in the cytosol. PKC
      beta(1) and delta isoforms particulate levels were significantly higher both in
      ischemic and in reperfused samples than in the controls. Conversely, following
      reperfusion, PKC beta(2) and epsilon isoforms displayed a reduction in their
      particulate to total level ratios. The intracellular calcium chelator, 1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, 1mM, but not the N-methyl-d
      asparate receptor antagonist, MK-801, 1muM, prevented the translocation of
      beta(1) isoform observed during ischemia. Both drugs were effective in
      counteracting reperfusion-induced changes in beta(2) and epsilon isoforms,
      suggesting the involvement of glutamate-induced calcium overload. These findings
      demonstrate that: (i) PKC isoforms participate differently in
      neurotoxicity/neuroprotection events; (ii) the changes observed following
      chemical ischemia are pharmacologically modulable; (iii) the protocol of in vitro
      chemical ischemia is suitable for drug screening.

PMID- 16963163
TI  - CCK-8 induces NGF and BDNF synthesis and modulates TrkA and TrkB expression in
      the rat hippocampus and septum: Effects on kindling development.
AB  - In our previous studies, we demonstrated that intraperitoneal (i.p.) injections
      with the neurotransmitter/neuromodulatory peptide Cholecystokinin-8 (CCK-8)
      stimulate the synthesis of the neurotrophin nerve growth factor (NGF) resulting
      in the structural and functional recovery of neuronal damage. This neurotrophin
      mediated neuroprotective action of CCK-8 has opened a new perspective for a
      better understanding of the CCK neurobiological and pharmacological properties.
      To explore the possible beneficial effects of the CCK-induced increase of
      neurotrophin availability in brain, we compared the effects of i.p. CCK-8 in
      healthy rats and in a chemical kindling model using a subconvulsive dose of
      pentylenetetrazol (PTZ). Behavioural changes were monitored during treatment and
      classified according to a six-point scale. After 3 weeks of treatment (12
      trials), the PTZ group of rats manifested generalized clonic-tonic seizures
      (Class 5 behaviour). For this reason, this time point was chosen to compare the
      effects of CCK-8 treatment on the expression of NGF, the brain derived
      neurotrophin factor (BDNF) and their receptors in the septum and hippocampus. We
      found that repeated i.p. injections with CCK-8 in adult rats result in: (1) an
      increase of NGF and BDNF protein and mRNA levels in the septum and hippocampus;
      (2) a down-regulation of TrkA and p75NTR and an up-regulation of TrkB; (3)
      reduced susceptibility to develop chemical kindling; (4) recovery of the PTZ
      induced changes in the expression of neurotrophin receptors in the septal and
      hippocampal tissues. This data clearly indicates that CCK-induced variation of
      neurotrophin synthesis in brain is able to influence the susceptibility to
      develop seizures in adult rats most probably by counteracting the progressive
      neuronal dysfunction and/or damage.

PMID- 16963164
TI  - Age-dependent axonal degeneration in an Alzheimer mouse model.
AB  - Some neurodegenerative diseases including Alzheimer's disease (AD) and
      amyotrophic lateral sclerosis (ALS) exhibit prominent defects in axonal
      transport. These defects can manifest as axonal swellings or spheroids, which
      correspond to axonal enlargements and aberrant accumulation of axonal cargoes,
      cytoskeletal proteins and lipids. Recently, a controversial scientific debate
      focussed on the issue whether Abeta serves as a trigger for aberrant axonal
      transport in the pathophysiology of AD. Prominent axonopathy has been shown to be
      induced by overexpression of proteins involved in several neurodegenerative
      diseases. Neurofilament, apolipoprotein E, Niemann-Pick protein and Tau
      transgenic mice with axonal trafficking deficits have been reported. Furthermore,
      motor deficits are frequently observed in patients with AD, which has been
      attributed to the typical tauopathy in post-mortem brain tissue. In the present
      report, we analyzed axonal neuropathology in the brain and spinal cord of a
      transgenic mouse model with abundant intraneuronal Abeta42 production and provide
      compelling evidence for axonal degeneration. The APP/PS1ki mice showed
      characteristic axonal swellings, spheroids, axonal demyelination and ovoids,
      which are myelin remnants of degenerated nerve fibers in an age-dependent manner.
      Abundant accumulation of intraneuronal N-modified Abeta, Thioflavin S-positive
      material and ubiquitin was found within the somatodendritic compartment of
      neurons. We conclude that the intraneuronal accumulation of Abeta-amyloid
      peptides is followed by axonal degeneration, and thus might be a causative factor
      for the axonal changes seen in AD.

PMID- 16963165
TI  - Granulocyte macrophage colony-stimulating factor as an adjuvant for hepatitis B
      vaccination: a meta-analysis.
AB  - The efficacy of granulocyte macrophage colony-stimulating factor (GM-CSF) to
      enhance the immune response to hepatitis B virus vaccine has been object of
      several reports. We searched for randomized controlled clinical trials comparing
      GM-CSF given concomitantly to hepatitis B virus vaccine to vaccine given alone or
      with placebo. Data on rates of seroconversion (anti-HBs titers >10 IU/ml) from 13
      studies (734 subjects) produced combined estimates that favored GM-CSF as
      compared to controls: rate ratio after a single immunization was 1.54 [95%
      confidence interval (CI), 1.04-2.27] and 1.20 (95% CI, 1.02-1.42) at the end of
      the vaccination cycle. Using a logistic approach a significant dose/response
      effect of GM-CSF was seen. Moreover, in renal failure patients who have responded
      to the vaccine, GM-CSF increased anti-HBs titers. Our findings suggest that GM
      CSF induced a significant effect in terms of response rate and achievement of an
      earlier seroconversion to the vaccine in the overall populations examined, in
      renal failure patients and in healthy individuals.

PMID- 16963166
TI  - Concentration ratios for small mammals collected from the exposed sediments of a
      137Cs contaminated reservoir.
AB  - (137)Cs concentration ratios were computed for small mammals collected from the
      dried sediments of a partially drained, contaminated reservoir. Soil (137)Cs
      activity concentrations were heterogeneous on small and large spatial scales and
      had a geometric mean of 253 (range 23-2110) Bq/kg dry weight. Mean (137)Cs
      activity concentrations in composite cotton rat Sigmodon hispidus and cotton
      mouse Peromyscus gossypinus samples averaged 2480 (range 556-6670) and 471 (range
      96-1000) Bq/kg whole body dry weight, respectively. About 50% of the variance in
      cotton rat tissue (137)Cs activity was explained by variation in soil (137)Cs
      activity. Soil-to-animal dry weight concentration ratios averaged 6.0 for cotton
      rats and 1.2 for cotton mice and were generally similar to (137)Cs concentration
      ratios for herbivorous, homeothermic animals from other contaminated ecosystems.
      In the RESRAD-BIOTA dose model, the default wet-weight concentration ratio for
      (137)Cs in terrestrial animals is 110 resulting in an estimate of internal and
      external radiation doses to terrestrial biota that is 44 times more than the dose
      calculated with the actual measured wet-weight concentration ratio for cotton
      rats (1.6). These results show that site-specific concentration ratios can
      significantly affect the estimation of dose.

PMID- 16963167
TI  - Continuity of care and the European working time directive: a maxillofacial
      perspective.
AB  - The European Working Time Directive (EWTD) was introduced in 1993 and was
      heralded as both a challenge and an opportunity for the NHS to modernize its
      services Continuity of care is usually viewed as the ongoing relationship between
      a patient and a single practitioner. Fragmentation of this continuity by many
      doctors being involved in a patient's management may weaken this relationship.
      The effect of the EWTD on junior doctors training in various specialities is well
      studied, we however were interested to assess the effect of the EWTD on the
      patient-doctor relationship in a maxillofacial setting and aimed for this paper
      to serve as an indicator of current practice and facilitate future research in
      this area. Seventy-five consecutive patients were studied with 72 patient
      proformas analysed. Our findings show greater same consultant patient contact
      than that of the specialist registrars and senior house officers. We feel that
      this is largely due to new work patterns introduced through the advent of the
      EWTD.

PMID- 16963168
TI  - Environmental contaminants in arctic foxes (Alopex lagopus) in Svalbard:
      relationships with feeding ecology and body condition.
AB  - Adipose tissues from 20 arctic foxes (Alopex lagopus) of both sexes from Svalbard
      were analysed for polybrominated diphenyl ether (PBDE), polychlorinated biphenyl
      (PCB), p,p'-dichlorodiphenyltrichloroethane (DDE), chlordane, and
      hexachlorobenzene (HCB) concentrations. Gender (0.43<p<0.97) and age
      (0.15<p<0.95) were not significantly related to any of the organohalogen groups.
      Body condition showed a significant inverse relationship with SigmaPBDE,
      SigmaChlordane and HCB, suggesting that increased tissue contaminant
      concentrations are associated with depletion of adipose tissue. The seasonal
      cyclic storage and mobilisation of adipose tissue, characteristic in Arctic
      wildlife, may then provide increased input of contaminants to sensitive, vital
      effect organs. Trophic position was estimated by delta(15)N from muscle samples
      and showed significantly positive relationship with all contaminants, with the
      exception of HCB concentrations. This indicates that foxes feeding at high
      trophic levels had higher tissue contaminant levels as a result of
      bioaccumulation in the food chain.

PMID- 16963169
TI  - Mechanisms of silica-induced IL-8 release from A549 cells: initial kinase
      activation does not require EGFR activation or particle uptake.
AB  - Understanding how mineral particles trigger cellular responses is crucial in
      order to elucidate what characteristics determine their harmful effects. It is
      not clear whether cellular effects are triggered through the cell membrane or
      require particle uptake. However, studies with asbestos suggest that activation
      of the epidermal growth factor receptor (EGFR) may be important. We have
      previously reported that crystalline silica-induced interleukin (IL)-8 release
      from human lung epithelial cells (A549) was regulated through Src family kinases
      (SFKs) and the mitogen-activated protein kinases (MAPKs) p38 and extracellular
      signal-regulated kinase (ERK)-1 and -2. The present study shows that SFK and p38
      phosphorylation increased almost immediately upon crystalline silica exposure,
      whereas ERK1/2 phosphorylation increased after 10 min of exposure. The p38
      inhibitor SB202190 increased the silica-induced ERK1/2 phosphorylation suggesting
      that p38 activity may attenuate activation of ERK1/2. Scanning electron
      microscopy showed that some silica particles were phagocytosed between 1 and 4h
      of exposure, but that the majority remained bound by microvilli on the cell
      surface. The EGFR inhibitor AG1478 attenuated both silica-induced IL-8 release
      and phosphorylation of SFKs and ERK1/2. However, AG1478 also inhibited the
      respective background levels, and the EGFR was not phosphorylated at the onset of
      silica exposure. The results suggest that crystalline silica triggers p38 and SFK
      ERK1/2 signaling through interactions with membrane components as both pathways
      were rapidly activated prior to particle internalization. However, the silica
      induced up-regulation of IL-8 release through the SFK-ERK1/2 pathway does not
      appear to be initiated through activation of the EGFR, although basal EGFR
      activity may affect the magnitude of the responses.

PMID- 16963170
TI  - The mouse lymphoma thymidine kinase assay for the assessment and comparison of
      the mutagenic activity of cigarette mainstream smoke particulate phase.
AB  - The mouse lymphoma thymidine kinase assay (MLA) has been optimized to
      quantitatively determine the in vitro mutagenicity of cigarette mainstream smoke
      particulate phase. To test whether the MLA is able to discriminate between
      different cigarette types, specially constructed cigarettes each containing a
      single tobacco type - Bright, Burley, or Oriental - were investigated. The
      mutagenic activity of the Burley cigarette was statistically significantly lower,
      up to approximately 40%, than that of the Bright and Oriental cigarettes. To
      determine the impact of two different sets of smoking conditions, American-blend
      cigarettes were smoked under US Federal Trade Commission/International
      Organisation for Standardisation conditions and under Massachusetts Department of
      Public Health (MDPH) conditions. Conventional cigarettes - eight from the US
      commercial market plus the Reference Cigarettes 1R4F and 2R4F - and an
      electrically heated cigarette smoking system (EHCSS) prototype were tested. There
      were no statistically significant differences between the two sets of smoking
      conditions on a per mg total particulate matter basis, although there was a
      consistent trend towards slightly lower mutagenic activity under MDPH conditions.
      The mutagenic activity of the EHCSS prototype was distinctly lower than that of
      the conventional cigarettes under both sets of smoking conditions. These results
      show that the MLA can be used to assess and compare the mutagenic activity of
      cigarette mainstream smoke particulate phase in the comprehensive toxicological
      assessment of cigarette smoke.

PMID- 16963172
TI  - Influence of naltrexone administration on dehydroepiandrosterone sulfate levels
      in male and female participants.
AB  - Dehydroepiandrosterone sulfate (DHEAS) is an excitatory neurosteroid with anti
      glucocorticoid properties. Endogenous opioid system blockade is known to activate
      the hypothalamic-pituitary-adrenal axis and other hormonal systems. However, the
      literature is sparse regarding the extent to which this blockade acutely
      influences DHEAS activity. Further, the stability of DHEAS concentrations across
      short term laboratory studies is not well established. The current study examined
      these issues in human participants. Using a double-blind, counterbalanced design,
      50mg of naltrexone and placebo were administered. Repeated salivary samples were
      then obtained over a 3h period while participants completed a nociceptive testing
      paradigm. DHEAS and cortisol concentrations were determined. Naltrexone
      administration was associated with an increase in cortisol concentrations;
      however, DHEAS was unaffected by naltrexone and did not vary across the course of
      the study. This finding is an important contribution to the methodological
      literature, and may be used to verify the stability of DHEAS for future
      investigations.

PMID- 16963171
TI  - A prospective randomised clinical trial of one bis-GMA-based and two ormocer
      based composite restorative systems in class II cavities: three-year results.
AB  - OBJECTIVES: Ormocer composites, consisting of a silicon-based polymer, have been
      developed recently as a tooth-coloured restorative material. The purpose of this
      prospective randomised clinical trial was to evaluate the performance of two
      small-particle hybrid ormocer-based restorative systems (AD, Admira/Admira Bond,
      VOCO; DE, Definite/Etch & Prime 3.0, Dentsply) and one small-particle hybrid bis
      GMA-based composite restorative system (TC, Tetric-Ceram/Syntac, Ivoclar
      Vivadent) in occlusal stress-bearing restorations. METHODS: One hundred and
      twenty-eight occlusal-proximal restorations (44 AD, 43 DE and 41 TC) were placed
      according to the manufacturer's instructions in thirty-two adult patients. Their
      clinical performance was scored according to the USPHS criteria and evaluation of
      bite-wing radiographs. RESULTS: After 3 years, four AD, five DE and four TC
      restorations had failed due to fracture or marginal gap formation. Surface
      roughness improved significantly when compared to the baseline in AD and TC
      (Friedman test, p<0.05) during the first year but returned to baseline values
      after 3 years. DE had a significant tendency towards discolouration (p<0.05).
      Bite-wing radiographs showed two AD and one TC restorations with internal
      porosities. ANOVA showed that larger restorations (> or = 3 surfaces) showed
      significantly more degradation than smaller ones. CONCLUSIONS: In a group of
      class II restorations, there was no significant difference in failures after 3
      years between ormocer-based and bis-GMA-based restorative systems.

PMID- 16963174
TI  - Use of a progestogen only preparation containing desogestrel in the treatment of
      recurrent pelvic pain after conservative surgery for endometriosis.
AB  - OBJECTIVE: To assess the effect of a new progestin progestogen only pill
      (desogestrel) versus an oral contraceptive in the treatment of recurrent
      endometriosis. STUDY DESIGN: A randomized prospective clinical study. A group of
      women with endometriosis (n=40) who showed recurrent dysmenorrhea and/or pelvic
      pain after conservative surgery, and did not desire a pregnancy. Continuous
      treatment for 6 months with desogestrel (75 microg/d) (n=20) versus a combined
      oral contraceptive (ethinyl estradiol 20 microg plus desogestrel 150 microg)
      (n=20) was performed. RESULTS: A significant improvement of both pelvic pain and
      dysmenorrhea was observed following each type of treatment (P<0.001). The use of
      desogestrel progestogen only pill was associated with a breakthrough bleeding in
      20% patients, while a significant body weight increase was observed in 15% after
      oral contraceptive. CONCLUSIONS: Both desogestrel and an oral estro-progestinic
      were effective, safe and low cost therapy of pain symptoms after endoscopic
      surgery for endometriosis, the former showing an impact on breakthrough bleeding,
      the later an incidence on body weight increase.

PMID- 16963176
TI  - Identifying crop vulnerability to groundwater abstraction: modelling and expert
      knowledge in a GIS.
AB  - Water use is expected to increase and climate change scenarios indicate the need
      for more frequent water abstraction. Abstracting groundwater may have a
      detrimental effect on soil moisture availability for crop growth and yields. This
      work presents an elegant and robust method for identifying zones of crop
      vulnerability to abstraction. Archive groundwater level datasets were used to
      generate a composite groundwater surface that was subtracted from a digital
      terrain model. The result was the depth from surface to groundwater and
      identified areas underlain by shallow groundwater. Knowledge from an expert
      agronomist was used to define classes of risk in terms of their depth below
      ground level. Combining information on the permeability of geological drift types
      further refined the assessment of the risk of crop growth vulnerability. The
      nature of the mapped output is one that is easy to communicate to the intended
      farming audience because of the general familiarity of mapped information. Such
      Geographic Information System (GIS)-based products can play a significant role in
      the characterisation of catchments under the EU Water Framework Directive
      especially in the process of public liaison that is fundamental to the setting of
      priorities for management change. The creation of a baseline allows the impact of
      future increased water abstraction rates to be modelled and the vulnerability
      maps are in a format that can be readily understood by the various stakeholders.
      This methodology can readily be extended to encompass additional data layers and
      for a range of groundwater vulnerability issues including water resources,
      ecological impacts, nitrate and phosphorus.

PMID- 16963178
TI  - Testicular cancer variations in time and space in Europe.
AB  - OBJECTIVES: Testicular cancer (TC) is the most common malignancy in young men. A
      review of all published articles on TC incidence revealed an increased incidence
      in Northern and Central Europe. We extended the analysis to the whole of Europe
      by using all data available, notably from registries. METHODS: We performed a
      PubMed search and selected articles dealing with TC incidence. We obtained
      additional information from data of European registries through the eight volumes
      of the Cancer Incidence in Five Continents, IARC Scientific Publications.
      RESULTS: Since the Second World War, TC incidence has been increasing in nearly
      all European countries. It has doubled in several countries, including France,
      since 1970. We observed that the increase followed a gradient: the highest rate
      is centred in Denmark and Germany, and decreases progressively in a centrifugal
      manner. CONCLUSIONS: TC incidence is increasing throughout Europe, but wide
      discrepancies exist between the different countries. The reasons for such a
      phenomenon are still unclear although environmental factors are strongly
      suspected, which could have an impact on male fertility. From a public health
      perspective, further research using cases collected through national and regional
      population-based registers and case-control studies must be strongly encouraged.

PMID- 16963179
TI  - New frontiers in intravesical therapies and drug delivery.
AB  - OBJECTIVES: The intravesical route permits site-specific delivery of drugs with a
      reduced side-effect profile as compared to oral delivery systems, either by
      avoiding first-pass metabolism or by obtaining a local effect. We investigated
      mechanisms related to urothelium permeability and new physical and chemical
      developments in intravesical drug delivery that potentially permit successful
      treatment of several bladder dysfunction. METHODS: A literature review. RESULTS:
      Pharmacologic agents increasing urothelial permeability and useful for clinical
      purposes have been described, such as dimethylsulfoxide, protamine sulphate,
      chitosan, and nystatin. Among physical approaches, electromotive drug
      administration appears to be more effective than intravesical passive diffusion
      in delivering drugs through the urothelium into deeper layers of the bladder.
      Experimental and clinical reports demonstrated that electric current
      significantly increases the transport of local anaesthetics, mytomicin C,
      oxybutynin, resiniferatoxin, epinephrine, and dexamethasone. Among new chemical
      approaches, cell-penetrating peptides posses the ability to translocate
      macromolecular drugs across membranes of urothelial cells. The therapeutic
      benefits of sustained delivery afforded by thermosensitive hydrogel, which forms
      a depot for hydrophilic and hydrophobic drugs, have been demonstrated by
      delivering anti-inflammatory drugs. Liposomes improve the aqueous solubility of
      several hydrophobic drugs such as taxol, amphotericin, and capsaicin.
      CONCLUSIONS: Electromotive drug administration, new in situ delivery systems, and
      bioadhesive liposomes may make it possible to extend intravesical therapy and
      drug administration to many bladder diseases. Research to expand knowledge of the
      chemical and physical properties of the bladder and processes regulating drug
      transport across biologic membranes is needed to make this a reality.

PMID- 16963180
TI  - Enrichment and ecosystem stability: effect of toxic food.
AB  - Enrichment in resource availability theoretically destabilizes predator-prey
      dynamics (the paradox of enrichment). However, a minor change in the resource
      stoichiometry may make a prey toxic for the predator, and the presence of toxic
      prey affects the dynamics significantly. Here, theoretically we explore how, at
      increased carrying capacity, a toxic prey affects the oscillation or
      destabilization of predator-prey dynamics, and how its presence influences the
      growth of the predator as well as that of a palatable prey. Mathematical analysis
      determines the bounds on the food toxicity that allow the coexistence of a
      predator along with a palatable and a toxic prey. The overall results demonstrate
      that toxic food counteracts oscillation (destabilization) arising from enrichment
      of resource availability. Moreover, our results show that, at increased resource
      availability, toxic food that acts as a source of extra mortality may increase
      the abundance of the predator as well as that of the palatable prey.

PMID- 16963181
TI  - Rugosin E, an ellagitannin, inhibits MDA-MB-231 human breast cancer cell
      proliferation and induces apoptosis by inhibiting nuclear factor-kappaB signaling
      pathway.
AB  - In this study, we first report the chemopreventive effect of rugosin E in human
      breast cancer cell line, MDA-MB-231. Treatment with rugosin E decreased the cell
      proliferation of MDA-MB-231 cells in a dose-dependent manner. Rugosin E treatment
      arrested MDA-MB-231 cells at G0/G1 phase. This effect was strongly associated
      with concomitant decrease in the level of cyclin D1, cyclin D2, cyclin E, cdk2,
      cdk4, and cdk6, and increase of p21/WAF1. In addition, rugosin E also induced
      apoptotic cell death. Rugosin E increased in the expression of Bax, Bak, and Bcl
      Xs, but decreased the levels of Bcl-2 and Bcl-X(L), and subsequently triggered
      mitochondria apoptotic pathway (release of cytochrome c, activation of caspase-9,
      and caspase-3). In addition, pre-treatment of cells with caspase-9 inhibitor
      blocked rugosin E-induced cell proliferation and apoptosis, indicating caspase-9
      activation was involved in rugosin E-mediated MDA-MB-231 cells apoptosis. Rugosin
      E inhibited the constitutively activated and inducible NF-kappaB in both its DNA
      binding activity and transcriptional activity. Furthermore, rugosin E also
      inhibited the TNF-alpha-activated NF-kappaB-dependent reporter gene expression of
      cyclin D1, c-Myc, XIAP, Bcl-2, and Bcl-X(L) were all downregulated by rugosin E.
      Our results indicated that rugosin E inhibits the activation of NF-kappaB, and
      this may provide a molecular basis for drug development in the prevention and
      treatment of cancer by rugosin E.

PMID- 16963182
TI  - Integrated pollution prevention and control for heavy ceramic industry in Galicia
      (NW Spain).
AB  - The heavy ceramic industry (building materials and refractory products
      manufacture) is an important source of pollutants to the environment. For this
      reason these industrial sub-sectors are included in prevention and control
      pollution policies, specifically those of the European Union. The IPPC Directive
      pays particular attention to the mineral industries, not least to the ceramic
      industry (epigraph 3.5, Annex I). In this paper, a methodology which is being
      applied to support IPPC installations and the competent administrative authority
      in Galicia (NW Spain) is presented. For that, the Galician heavy ceramic industry
      is analysed, as also are the ways to study the Best Available Techniques (BAT)
      with a view to establishing the emission limit values (ELV) for each specific
      case. Hence, a technological state of the art has been carried out for both sub
      sectors, from the point of view of implementation of the IPPC in Galicia.
      Following this, the processes are described briefly and an analysis of the
      consumption and emission levels of the main pollutants is made. An inventory that
      includes the best environmental practices and the preventive and abatement
      candidate techniques as BAT was elaborated for both considered sub-sectors. An
      information data sheet for each candidate BAT is presented as a method to help
      both the industries and the competent authority to identify a candidate technique
      of the inventory as BAT. Three illustrative examples of the application of this
      procedure are presented for different emissions to environmental media for
      Galician installations.

PMID- 16963184
TI  - Placebo analgesia is accompanied by large reductions in pain-related brain
      activity in irritable bowel syndrome patients.
AB  - Previous experiments found that placebos produced small decreases in neural
      activity of pain-related areas of the brain, yet decreases were only
      statistically significant after termination of stimuli and in proximity to when
      subjects rated them. These changes could reflect report bias rather than
      analgesia. This functional magnetic resonance imaging (fMRI) study examined
      whether placebo analgesia is accompanied by reductions in neural activity in pain
      related areas of the brain during the time of stimulation. Brain activity of
      irritable bowel syndrome patients was measured in response to rectal distension
      by a balloon barostat. Large reductions in pain and in brain activation within
      pain-related regions (thalamus, somatosensory cortices, insula, and anterior
      cingulate cortex) occurred during the placebo condition. Results indicate that
      decreases in activity were related to placebo suggestion and a second factor
      (habituation/attention/conditioning). Although many factors influence placebo
      analgesia, it is accompanied by reduction in pain processing within the brain in
      clinically relevant conditions.

PMID- 16963183
TI  - The relationship of adult attachment dimensions to pain-related fear,
      hypervigilance, and catastrophizing.
AB  - Despite the prominence of fear-avoidance models of chronic pain, there is a
      paucity of research regarding the origins of pain-related fear. Based on the
      premise that insecure attachment could be a developmentally based origin of
      elevated fear of pain, associations between adult attachment dimensions and
      constructs included in fear-avoidance models of chronic pain were investigated.
      Consistent with Bartholomew and Horowitz's [Bartholomew K, Horowitz LM.
      Attachment styles among young adults: a test of a four-category model. J Pers Soc
      Psychol 1991;61:226-44.] model, attachment was conceptualized as being comprised
      of a model of self dimension (i.e., degree of anxiety regarding rejection based
      on beliefs of personal unworthiness) and a model of others dimension (i.e.,
      degree of interpersonal mistrust and discomfort with interpersonal closeness). A
      large university student sample free of chronic pain (N=278) completed a measure
      of adult romantic attachment (i.e., Experiences in Close Relationships
      Questionnaire; [Brennan KA, Clark CL, Shaver PR. Self-report measurement of adult
      attachment: an integrative overview. In: Simpson JA, Rholes WS, editors.
      Attachment theory and close relationships. New York: The Guilford Press, 1998. p.
      46-76.]), the Fear of Pain Questionnaire-III [McNeil DW, Rainwater AJ.
      Development of the fear of pain questionnaire - III. J Behav Med 1998;21:389
      410.], the Pain Vigilance and Awareness Questionnaire [McCracken LM. Attention to
      pain in persons with chronic pain: a behavioural approach. Behav Ther 1997;28:271
      84.], and the Pain Catastrophizing Scale [Sullivan MJ, Bishop SR, Pivik J. The
      pain catastrophizing scale: development and validation. Psychol Assess 1995;7:24
      532.]. It was hypothesized that insecure attachment would be positively
      associated with reports of pain-related fear, hypervigilance, and catastrophizing
      and that the model of self dimension would be the attachment variable most
      strongly associated with these variables. Correlation and multiple regression
      analyses supported these hypotheses. The model of self dimension had significant
      positive associations with each of the fear-avoidance constructs. The model of
      others dimension had a significant positive association with pain
      catastrophizing, but was not significantly associated with fear of pain and pain
      hypervigilance. Future research directions and potential clinical implications
      are discussed.

PMID- 16963185
TI  - Anti-allodynic effects of peripheral delta opioid receptors in neuropathic pain.
AB  - The analgesic effects of local administration of opioid agonists into peripheral
      tissues in alleviating pain have been well documented in both clinical and
      preclinical studies, although few studies have examined their effects in
      neuropathic pain. In this study, we investigated the anti-allodynic effects of
      peripherally acting delta opioid receptor (DOR) agonists in a rat model of
      neuropathic pain. Peripheral nerve injury (PNI) produced a time-dependent
      decrease in mechanical withdrawal thresholds that was attenuated by local
      administration into the hind paw of either morphine or the DOR agonist deltorphin
      II. Using Western blotting techniques, no change in DOR protein expression was
      detected in DRG ipsilateral to the site of injury compared to contralateral.
      However, an up-regulation of DOR protein was found in neuropathic DRG compared to
      sham, suggesting that there may be a bilateral increase in the expression of DOR
      following PNI. Results obtained from immunohistochemical studies confirmed up
      regulation in small and large DRG neurons in neuropathic compared to sham
      animals. Additionally, there was an increase in DOR protein within the
      ipsilateral sciatic nerve of neuropathic animals compared to sham and
      contralateral neuropathic conditions indicating the occurrence of receptor
      trafficking to the site of injury. Taken together, our findings suggest that
      functional peripheral DORs are present in sensory neurons following PNI and
      validate the development of selective DOR agonists for alleviating neuropathic
      pain.

PMID- 16963186
TI  - Chemical radiculitis.
AB  - The theory of chemical radiculitis had been put forward about 30 years ago, but
      as yet it has not been proved by clinical studies. The aim of the current studies
      was to determine whether the annular tear of a painful disc proved by discography
      is the cause of radiating leg pain (radiculopathy) in patients with discogenic
      low back pain. Forty-two patients with discogenic low back pain at single disc
      level with concomitant radiating leg pain were studied in order to analyse the
      relationship between site of annular tear and side of radiating leg pain.
      Electromyogram and motor nerve conduction velocity were monitored to examine
      nerve root injury. The current studies found that there was a significant
      positive correlation between the site of annular tear and the side of radiation
      pain. Abnormalities of electromyogram and reduction of motor nerve conduction
      velocity were found on the side of radiating leg pain. The studies indicated that
      leakage of chemical mediators or inflammatory cytokines, which are produced in
      the painful disc, into epidural space through annular tear could lead to injury
      to adjacent nerve roots, and it might constitute the primary pathophysiologic
      mechanism of radiating leg pain in patients with discogenic low back pain but
      with no disc herniation.

PMID- 16963188
TI  - Characterization of Saccharomyces cerevisiae Atm1p: functional studies of an ABC7
      type transporter.
AB  - Saccharomyces cerevisiae Atm1p has been cloned, over-expressed and purified from
      a yeast expression system. The sequence includes both the soluble ATPase and
      transmembrane-spanning domains. With the introduction of an N-terminal Kozak
      sequence and a C-terminal (His)(6)-tag, a yield of 1 mg of Atm1p was obtained
      from 3 g wet yeast cells, which is comparable to other membrane-associated
      proteins isolated from eukaryotic expression systems. The ATPase activity of
      Atm1p is sensitive to sodium vanadate, a P-type ATPase inhibitor, with an IC(50)
      of 4 microM. MgADP is a product inhibitor for Atm1p with an IC(50) of 0.9 mM. The
      Michaelis-Menten constants V(max), K(M) and k(cat) of Atm1p were measured as
      8.7+/-0.3 microM/min, 107+/-16 microM and 1.24+/-0.06 min(-1), respectively. A
      plot of ATPase activity versus concentration of Atm1p exhibits a nonlinear
      relationship, suggesting an allosteric response and an important role for the
      transmembrane domain in mediating both ATP hydrolysis and MgADP release. The
      metal dependence of Atm1p ATPase activity demonstrated a reactivity order of
      Mg(2+)>Mn(2+)>Co(2+), while each divalent ion was found to be inhibitory at
      higher concentrations. The activation and inhibitory effect of phospholipids
      suggest that formation of a lipid-micelle complex is important for enzymatic
      activity and stability. Structural analysis of Atm1p by CD spectroscopy suggested
      a similarity of secondary structure to that found for other members of this ABC
      protein family.

PMID- 16963187
TI  - Sterol 14alpha-demethylase cytochrome P450 (CYP51), a P450 in all biological
      kingdoms.
AB  - The CYP51 family is an intriguing subject for fundamental P450 structure/function
      studies and is also an important clinical drug target. This review updates
      information on the variety of the CYP51 family members, including their
      physiological roles, natural substrates and substrate preferences, and catalytic
      properties in vitro. We present experimental support for the notion that specific
      conserved regions in the P450 sequences represent a CYP51 signature. Two possible
      roles of CYP51 in P450 evolution are discussed and the major approaches for CYP51
      inhibition are summarized.

PMID- 16963189
TI  - Social experience influences hypothalamic oxytocin in the WHHL rabbit.
AB  - Social experience influences behavior and the progression of atherosclerosis in
      the Watanabe Heritable Hyperlipidemic (WHHL) rabbit, such that WHHL rabbits
      exposed to a consistent, stable social experience exhibited more affiliative
      social behavior and less aortic atherosclerosis compared to other social groups.
      Oxytocin (OT) has been implicated in the expression of social behavior, stress
      responses, and may provide a mechanism by which social experience influences
      atherogenesis in WHHL rabbits. The current study examined acute and chronic
      changes in central and peripheral OT before and after WHHL rabbits were exposed
      to one of three social conditions. Cannula implanted adjacent to the hypothalamic
      paraventricular nucleus (PVN) allowed chronic sampling of extracellular OT
      concentration via microdialysis. Rabbits were exposed to one of three social
      conditions: an Unstable group, with initially unfamiliar rabbits paired daily for
      4h during the initial week and similarly paired with a different, unfamiliar
      rabbit each week; a Stable group; with the same 2 littermates paired daily for 4h
      the entire study; and an Individually Caged group. Dialysates from the PVN and
      blood from the marginal ear vein were collected twice, 20 days apart, from
      rabbits before and after 2h of exposure to their respective social condition.
      Dialysates were assayed for OT and plasma was assayed for OT, catecholamines and
      glucocorticoids. There were no changes in PVN OT in any group following the
      initial social experience. In contrast, after 20 consecutive days of exposure to
      their respective social condition, PVN OT increased significantly in the Unstable
      group, but was relatively unchanged in the Stable group following the social
      experience on day 22. Peripheral OT was not altered in any group following the 2h
      social experience on day 1 or 22. The concentration of peripheral OT was the
      highest in the Stable group at all times. The Stable group also exhibited
      significantly less aortic atherosclerosis, consistent with earlier findings from
      our laboratory. Data from the present study suggest that the type of social
      experience WHHL rabbits are exposed influences PVN OT, social behavior and the
      progression of atherosclerosis in the WHHL rabbit model of disease.

PMID- 16963190
TI  - Behavioural epigenetics and psychiatric disorders.

PMID- 16963191
TI  - The inflammatory response recapitulates phylogeny through trophic mechanisms to
      the injured tissue.
AB  - The post-traumatic local acute inflammatory response is described as a succession
      of three functional phases of possible trophic significance: 1. Nervous or
      immediate (ischemia-reperfusion); 2. Immune or intermediate (infiltration by
      inflammatory and bacterial cells) and 3. Endocrine or late (angiogenesis with
      regeneration and/or cicatrization). Each of these phases emphasizes the trophic
      role of the mechanisms in the damaged tissue. Hence, the nervous phase is
      predominated by nutrition by diffusion; in the immune phase trophism is mediated
      by inflammatory cells and bacteria and, finally, in the endocrine phase, the
      blood circulation and oxidative metabolism play the most significant nutritive
      role. Since these trophic mechanisms are of increasing complexity, progressing
      from anoxia to total specialization in the use of oxygen to obtain usable energy,
      it could be speculated that they represent the successive reappearance of the
      stages that take place during the evolution of life on Earth, from ancient times
      without oxygen. In this sense, the inflammatory response could recapitulate
      phylogeny through the successive expression of pathophysiologic mechanisms that
      have a trophic meaning to the injured tissue.

PMID- 16963192
TI  - A revised timeline for biological agents: revisiting the early years of the germ
      theory of disease.
AB  - An agreed upon timeline for the initial, scientifically-informed use of
      biological agents typically begins with the Japanese Army in Manchuria and China
      prior to the generalized outbreak of World War II (1932 until 1945). The process
      included human experimentation with multiple biological agents followed by their
      release in combat (e.g. the plague bacillus) targeting military personnel and
      civilians. Two postulates are used support these dates. First, allegations of
      earlier bacteriological weapon experimentation and/or use represented the
      accidental, small scale, and sporadic dispersion of infectious agents preceding
      the Germ Theory of Disease. Therefore, attempts prior to the Twentieth Century
      were uninformed scientifically and are not considered representative. Later, as
      the Germ Theory was maturing, the hypothetical timeline was derived, in part
      retrospectively, from reputable historical sources (the Trillat Report and The
      League of Nations) published immediately upon the conclusion of World War I.
      These documents explicitly testified to the total absence of bacteriological
      weapons in any form (experimentation or battlefield application) directed at
      human subjects-in stark contrast to the utilization of chemical agents-during the
      course of that war. Therefore the Japanese Army in Manchuria became time zero.
      Recently, evidence previously hidden from outside study has surfaced
      demonstrating that a small group of Turkish physicians injected typhus
      contaminated serum into Armenian civilians during WWI. Although controversy
      persists regarding primary intent-immunization, experimentation on human
      subjects, or the introduction of a crude biological weapon-the discovery might
      suggest a revision to the accepted timeline. The primitive efforts with
      contaminated serum that occurred during the First World War may seem trivial,
      especially when compared to overall fatalities during that conflict, but they did
      include the informed and fatal application of microbial agents. Furthermore, the
      actions may have influenced certain behaviors that followed in World War II.

PMID- 16963193
TI  - Challenges in implementing a cervical screening program in South Africa.
AB  - BACKGROUND: The Cervical Health Implementation Project was initiated with the aim
      of developing and evaluating health system interventions for improving public
      sector cervical screening services. The project was conducted between January
      2001 and May 2003 in three districts in South Africa. This paper describes the
      districts, interventions and their evaluation, and discusses the implications of
      these findings for the roll out of a national cervical screening program.
      METHODS: A pretest/post-test study design was employed. The following
      interventions were developed and implemented: health worker training workshops,
      health system tools and protocols and a community awareness program. Pre- and
      post-intervention facility audits, key informant interviews, staff knowledge,
      attitude and practice (KAP) surveys and client KAP surveys were conducted. Clinic
      records and cytology laboratory data were reviewed. RESULTS: Service
      organization, availability of screening equipment and education and communication
      materials improved. The proportion of staff who knew the screening policy
      increased from 43% to 82%; and 68% of staff agreed with the screening policy
      after, as opposed to 23% before the intervention. In two of the districts,
      cytology turnaround times continued to be long. Only 50% of women with a high
      grade squamous intraepithelial lesion had a colposcopy and biopsy within 6 months
      of a Pap smear. Although the number of new smears performed in the three
      districts increased from 1544 in 2001 to 2801 in 2002, overall the coverage
      remained less than 4%. CONCLUSION: This project highlights the considerable
      challenges that need to be addressed to effectively implement the national
      screening policy.

PMID- 16963194
TI  - Women's perceptions and social barriers determine compliance to cervical
      screening: results from a population based study in India.
AB  - BACKGROUND: Success of cervical screening initiatives depends on high
      participation of the target population, which in turn is determined by the
      women's perceptions, health orientation and other socio-cultural issues. The
      present study identifies the immediate social and cultural barriers that prevent
      women to attend cervical screening facilities. METHODS: Women non-compliant to a
      community-based cervical screening program were identified. From them 500 were
      randomly selected for interview using a structured questionnaire that was
      designed on the basis of feedbacks received from several focused group
      discussions. Questionnaire listed 24 possible reasons for non-compliance. The
      women were asked to select the most pertinent reason(s) for her non-attendance or
      to reveal if they had any reason other than the listed ones. RESULTS: A total of
      469 non-compliant women were interviewed. They had significantly lower literacy
      rate compared to the compliant women (OR=2.25; 95% CI: 1.23-4.13). Nearly half of
      the interviewed women responded that they themselves opted to stay away from the
      program. Most common reasons cited for non-attendance in this group were
      reluctance to go for medical test in the absence of any symptoms and apprehension
      to have a test that detects cancer. Second major group of responders comprised of
      women who were willing, yet could not attend due to various hurdles. Most common
      hurdles were inability to leave household chores, pre-occupation with family
      problems and lack of approval from husbands. CONCLUSIONS: Modification of health
      behavior through education and social empowerment of women are essential for a
      population based cervical screening program to succeed in India.

PMID- 16963195
TI  - Psychosocial factors associated with the adherence to a colorectal cancer
      screening program.
AB  - BACKGROUND: Although colorectal cancer (CRC) is one of the most commonly
      diagnosed cancers and a major cause of cancer related mortality, very little is
      known about why screening adherence rates are low. First-degree relatives of CRC
      patients are the largest group of individuals at increased risk of CRC.
      Psychosocial factors related to CRC screening adherence were examined in a sample
      of siblings of individuals diagnosed with CRC. METHOD: To identify psychosocial
      factors related with participation in cancer screening examinations, 90 siblings
      of CRC patients were recruited. Adherence to screening by fecal occult blood
      test, flexible sigmoidoscopy and colonoscopy was the relevant factor.
      Sociodemographic variables, health locus of control (HLOC), perceived social
      support, knowledge about CRC and coping strategies were independent measures.
      RESULTS: Significant differences were found in age, gender, retirement status,
      knowledge of sibling's illness, HLOC-powerful others, coping strategies (positive
      thinking, blaming others, seeking social support), perceived social support types
      (listening, affective, material) and social support sources (friends, work
      colleagues and health staff). Using stepwise logistic regression, the strongest
      predictor of adherence was knowledge of sibling's illness. CONCLUSIONS: The
      findings suggest that effective strategies to increase participation in CRC
      screening may include efforts to improve knowledge of sibling's illness, material
      social support and advice from health staff.

PMID- 16963196
TI  - No association between XRCC1 and XRCC3 gene polymorphisms and breast cancer risk:
      Iowa Women's Health Study.
AB  - BACKGROUND: Genetic variation in DNA repair may contribute to differences in the
      susceptibility of several cancers. We evaluated two polymorphisms in the base
      excision repair pathway (BER) (XRCC1; Arg194Trp and Arg399Gln) and one
      polymorphism in the double strand DNA repair pathway (XRCC3; Thr241Met) for their
      association with breast cancer risk. METHODS: The association was analyzed in a
      nested case control study of 460 breast cancer cases and 324 cancer-free controls
      within the Iowa Women's Health Cohort. DNA was obtained from blood samples or
      paraffin embedded tissues (PET) and all samples were genotyped by one of three
      genotyping platforms-PCR-RFLP, PCR-INVADER, or Sequenom. RESULTS: None of the
      three polymorphisms studied were significantly associated with breast cancer risk
      (XRCC1: Arg194Trp (OR=1.21, 95% CI: 0.78-1.88); Arg399Gln (OR=1.20, 95% CI: 0.80
      1.79); XRCC3: Thr241Met (OR=1.04, 95% CI: 0.76-1.41). CONCLUSIONS: These results
      suggest that independently these polymorphisms of XRCC1 and XRCC3 genes do not
      contribute significantly to the genetic susceptibility of breast cancer.

PMID- 16963197
TI  - Nipple aspirate fluid color is associated with breast cancer.
AB  - BACKGROUND: Fluid can be non-invasively aspirated from the breast nipple (nipple
      aspirate fluid, NAF). NAF may have many colors, including clear, white, yellow,
      green, and red/brown. While bloody spontaneous nipple discharge has been linked
      with breast cancer, the association of NAF color with cancer is not established.
      Our hypothesis was that red/brown NAF color was associated with breast cancer.
      The purpose of this study was to assess (1) if red/brown NAF is associated with
      the presence and progression of breast cancer, (2) the influence of prior needle
      or surgical biopsy on NAF color, and (3) if an association between NAF color and
      breast cancer was found, to develop a cancer predictive model including NAF color
      and cytology, and clinical information. METHODS: Specimens were obtained from 848
      breasts between 1999 and 2004 after subjects enrolled in an IRB approved protocol
      to evaluate biologic markers of breast cancer. Cytologic evaluation was performed
      on Papanicolaou-stained cytospin preparations of NAF. RESULTS: Red/brown NAF was
      associated with breast cancer when considering all samples (p<0.001) and samples
      from women who did not undergo recent surgery (p=0.005). Needle biopsy did not,
      but surgical biopsy did influence NAF color. For the 327 women with NAF collected
      from both breasts, there was a significant association between red/brown NAF
      color and the presence of breast cancer (p=0.005). Red/brown NAF was more common
      in breasts with ductal carcinoma in situ than atypical hyperplasia (p=0.008). The
      optimal model, included NAF color, cytology, and age, was 92% sensitive and 61%
      specific in predicting if a woman had breast cancer. CONCLUSIONS: NAF color was
      associated with the presence of breast cancer and the progression from precancer
      to cancer in a population of women who presented to a breast cancer evaluation
      clinic. NAF color contributed to a highly predictive breast cancer detection
      model. Additional studies are warranted to determine the usefulness of NAF color
      in the assessment of women who present for breast cancer evaluation.

PMID- 16963198
TI  - Antimutagenic, antioxidant and antimicrobial properties of Maytenus krukovii
      bark.
AB  - The hydroalcoholic extract of Maytenus krukovii bark was investigated for its in
      vitro mutageno-protective activities by means of the Ames Salmonella/microsome
      assay. The extract showed an inhibitory effect in both T98 and T100 strains
      against the mutagenic activity of promutagen 2-aminoanthracene but was not
      protective against directly acting mutagens sodium azide and 2-nitrofluorene.
      When tested as a radical scavenger and antioxidant it produced a dose-dependent
      inhibition. The extract did not show significant antibacterial properties, and
      was weakly active against dermatophyte and phytopathogenic fungi, but inhibited
      the growth of phytopathogen Pithyum ultimum.

PMID- 16963199
TI  - Effects of beta-carotene supplementation on chick growth, immune status and
      behaviour in the grey partridge, Perdix perdix.
AB  - Carotenoids are important for various functions during chick development. Since
      these pigments cannot be synthesized, they can be considered limited resources
      that the mother optimally allocates between herself and her offspring (maternal
      effect). Some studies have examined the effects of carotenoids on growth and
      immune function but little is known about their role in behaviour. In this study
      of the grey partridge, we conducted two supplementation experiments: (1) laying
      females were fed with beta-carotene enriched or impoverished diets; (2) chicks
      were fed directly with beta-carotene enriched or impoverished diets. We then
      evaluated the effects of this carotenoid on chick growth, immunocompetence and
      anti-predator behaviour (reactions to a raptor model). In the first experiment,
      the beta-carotene enriched diet given to mothers did not cause any difference in
      chick physiology. In the second experiment, beta-carotene supplementation of
      chicks had a significant beneficial effect on their growth and immune response,
      although their behavioural reactions did not differ in relation to the diet.
      Therefore, beta-carotene supplementation had beneficial effects on growth and
      immunocompetence only when directly supplied to chicks. The beneficial effect
      reported in other species for begging or pecking behaviours was not confirmed for
      the anti-predator behaviour of grey partridge chicks.

PMID- 16963200
TI  - A unique amino acid substitution, T126I, in human genotype C of hepatitis B virus
      S gene and its possible influence on antigenic structural change.
AB  - Amino acid substitutions in the S gene of hepatitis B virus (HBV), especially in
      the 'a' determinant region, have been suggested to affect the antigenicity of the
      virus and the clinical outcome of the infected patient. However, no convincing
      evidence has been presented for this hypothesis, partly because the 3D structure
      of the S protein has not been determined. Comparative analysis of viral genes
      offers an approach to testing this hypothesis, as it may reveal signals of
      natural selection and provide insights into the functional significance of the
      observed amino acid substitutions. In this study, we analyze HBV S gene sequences
      obtained from 24 patients infected with HBV genotypes B or C, together with 16
      representative viral strains of HBV genotypes A-F retrieved from GenBank. We use
      phylogenetic methods to infer evolutionary changes among HBV genotypes and to
      identify amino acid residues potentially under positive selective pressure.
      Furthermore, we employ the fragment assembly method to predict structural changes
      in the S protein. The results showed that an amino acid substitution within the
      'a' determinant, T126I, was unique to genotype C, may affect the antigenicity of
      the HBsAg, and may result in poorer clinical outcomes of patients infected with
      genotype C viral strains. We suggest that an integrated approach of evolutionary
      comparison and structural prediction is useful in generating hypotheses for
      further laboratory validation.

PMID- 16963201
TI  - Uterine and serum cytokine arrays in the mouse during estrus.
AB  - Cytokines govern uterine immunology and embryo receptivity and are increasingly
      recognized for their embryotrophic roles. While supplementing culture media with
      cytokines may improve embryo development/viability in vitro, little is known
      about their physiological profiles in vivo, and hence which are likely to be
      uterine immunoregulators and embryotrophins. Therefore, this study profiled 23
      cytokines in uterine fluid and serum from individual naturally cycling estrous
      mice. Samples were analyzed by fluid-phase multiplex immunoassays for interleukin
      (IL)-1alpha, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IL-12 (p40), IL-12
      (p70), IL-13, IL-17, eotaxin, granulocyte-colony stimulating factor (G-CSF),
      granulocyte macrophage-colony stimulating factor (GM-CSF), interferon (IFN)
      gamma, keratinocyte-derived chemokine (KC), monocyte chemoattractant protein
      (MCP)-1, macrophage inflammatory protein (MIP)-1alpha MIP)-1beta regulated upon
      activation, normal T-cell expressed and secreted (RANTES) and tumor necrosis
      factor (TNF)-alpha. There was a marked divergence in cytokine concentrations
      between uterine fluid and serum. The former was dominated by G-CSF, eotaxin, KC
      and IL-1alpha, and had significantly higher levels of IL-1beta, IL-2, IL-3, IL-4,
      IL-6, IL-9, GM-CSF, MIP-1alpha, MIP-1beta and RANTES. Serum had significantly
      higher IL-12 (p40), IL-12 (p70), IL-17 and IFN-gamma concentrations. No
      significant differences in IL-5, IL-10, IL-13, MCP-1 or TNF-alpha profiles were
      noted. These data indicated a strict compartmentalization of uterine cytokines,
      with G-CSF as a major cytokine at estrous. Results are discussed with respect to
      immune cell function, post-coital paternal antigen processing, estrous cyclicity,
      and endometrial angiogenesis, cell turnover and differentiation.

PMID- 16963202
TI  - Caprine luteinizing hormone isoforms during the follicular phase and anestrus.
AB  - The relative proportion of the circulating luteinizing hormone isoforms in goats
      during follicular phase (pre-ovulatory peak; F) and anestrus (A) was
      investigated. Estrus was synchronized in six goats with a prostaglandin analogue.
      After estrus was detected, blood samples were taken at 1 h intervals for 24 h.
      Four anestrous goats received 100 microg i.v. of GnRH and blood samples were
      collected every 15 min for 5 h. Samples with the greatest LH concentration in
      follicular phase and after GnRH administration (anestrus) were analyzed by
      chromatofocusing and eluted with a pH gradient from 10.5 to 3.5. For
      quantification purposes eluted LH was grouped into basic (pH> or =7.5), neutral
      (pH 7.4-6.5) and acidic isoforms (pH< or =6.4) as well as by pH unit. In both
      physiological conditions (PC), basic and acidic isoforms were greater than the
      neutral. With this grouping criteria, there was an interaction between PC and pH
      group, with the proportion of neutral isoforms being greater (p<0.05) in A
      (12.0+/-0.8%) as compared with F (5+/-2%). Analysis by pH unit showed a very
      basic group of eluted isoforms (pH> or =10), which amounted to a percentage of
      6.0+/-0.4% of the total observed during A, and 3+/-1% during F (p<0.05).
      Predominant isoforms in A eluted in the pH range 9.99-9.0 (42+/-3%) as compared
      to 7+/-3% (p<0.01) in that pH range in F. In contrast, the predominant isoforms
      in F eluted in the pH range 8.99-8.0, representing 55+/-8%, while in A the
      proportion was 11+/-2% (p<0.01). Isoforms eluted at the pH range 7.9-7
      represented a significantly greater proportion during A (5.0+/-0.6%) as compared
      with F (3+/-1%). This is the first report on goat LH circulating isoforms. During
      A the LH isoforms secreted by the pituitary are more basic than during F.

PMID- 16963203
TI  - Embryo survival in dairy cows managed under pastoral conditions.
AB  - Efficient pasture-based milk production systems require a compact calving pattern
      aligned to the onset of the grazing season, a 365-day calving interval and low
      culling rates for infertility. Achievement of these targets requires high herd
      reproductive performance. While high genetic merit Holstein cows produce more
      milk in grass-based systems their fertility is compromised. Management of the
      modern high genetic merit Holstein dairy cow presents a major challenge in
      pasture-based systems of production. It appears that the extent of early embryo
      loss is greater (up to 20% points greater) in the modern high-producing dairy cow
      and that a much higher proportion of the embryos die before day 7 following
      insemination in contrast to heifers and lower yielding cows. About 7-8% of
      pregnancies are lost between days 30 and 90 of gestation with no evidence that
      loss rate is related to cow genetic merit, parity or level of production.
      Systemic concentrations of progesterone during both the cycle preceding and
      following insemination affect embryo survival rate with evidence that too low or
      indeed too high a concentration of progesterone been negatively associated with
      embryo survival rate. Peripheral concentrations of both progesterone and
      oestradiol are lowered by increased plane of feed intake due to increased
      metabolic clearance rate of the steroids, which is related to liver blood flow.
      It appears that high producing dairy cows have an increased risk of embryo death
      as a result of lowered peripheral concentrations of progesterone as a consequence
      of increased hepatic metabolism of progesterone. Uterine expression of mRNA for
      progesterone receptor, oestradiol receptor and retinol binding protein mRNA
      appears to be sensitive to changes in peripheral concentrations of progesterone
      during the first week after AI. It would appear that energy balance and dry
      matter intake during the 4 weeks, immediately after calving are critically
      important in determining conception rate when cows are inseminated at 70-100 days
      post-calving. Concentrate supplementation of cows at pasture during the breeding
      period has minimal affects on conception rates though sudden reduction in dietary
      intake should be avoided. For pasture-based systems of milk production more
      balanced breeding strategies, with greater emphasis on fertility and feed intake
      must be developed.

PMID- 16963204
TI  - Postmenopausal status, hypertension and obesity as risk factors for malignant
      transformation in endometrial polyps.
AB  - OBJECTIVES: We analyzed clinical data and pathological features of six cases of
      malignant endometrial polyps, to compare these with other examples reported in
      literature and to define the features of endometrial cancer arising in polyps.
      Moreover, to clarify the mechanisms of carcinogenesis in malignant endometrial
      polyps we examined the expression of cyclooxygenase-2 (COX-2), P53 and Ki 67 and
      their relationships with clinicopathologic characteristics. METHODS: The surgical
      pathology files of the Pathology Department of Parma University were searched for
      cases of endometrial polyps with nests of endometrial carcinomas, from the years
      2002-2005. Clinical records, histological slides of endometrial curetting,
      hysterectomy with salpingo-oophorectomy specimens and pelvic lymph nodes were
      reviewed in each case. The main pathological features analyzed were histological
      types of endometrial cancer and the stage of development of neoplasm. The
      presence of other malignancies in the genital tract were also considered.
      Immunohistochemical staining was done using antibodies COX-2, p53 and Ki 67.
      RESULTS: In our study, all malignant endometrial polyps had been detected in
      postmenopausal women. The majority of our patients with malignant endometrial
      polyps had risk factors for the development of endometrial carcinoma such as
      hypertension, obesity and unopposed estrogen therapy. Unlike other studies, no
      patients had a history of previous breast carcinoma and Tamoxifen treatment. The
      most common subtypes of endometrial carcinoma in malignant polyps are
      endometrioid carcinoma and serous papillary carcinoma. Endometrial carcinoma
      arising in endometrial polyps is an early endometrial carcinoma with good
      prognosis, except for papillary serous carcinoma, which can be associated with
      multiple omental involvement, despite low stage of development in the uterus.
      Immunohistochemical study showed that COX-2 expression was found in cytoplasm of
      tumor cells and this was elevated in all cases, independently of the grade and
      the stage of development of the malignancy, histological subtype and deep
      invasion of myometrium. P53 and Ki 67 expression, detected in the nuclei of
      neoplastic cells, was not correlated with COX-2 immunoreactivity, but these
      markers were associated with more advanced stage, grading, and histologic
      subtypes of tumor. CONCLUSIONS: Postmenopausal status, hypertension, obesity
      could all be considered as risk factors for carcinomatous transformation within
      endometrial polyps in women without a history of breast carcinoma and Tamoxifen
      treatment. However, our series is small (only six cases considered) and further
      studies are necessary to confirm this hypothesis. In the current study,
      immunohistochemical data reveal that COX-2 expression may be associated with the
      carcinogenesis in endometrial carcinomas arising in endometrial polyps, but this
      antibody is not correlated with tumor aggressiveness, P53 and Ki 67 expression.
      P53 and Ki 67 overexpression, instead, are associated with advanced stage,
      histologic subtype and deep myometrial invasion of neoplasm.

PMID- 16963205
TI  - Female psychopathologic profile during menopausal transition: a preliminary
      study.
AB  - OBJECTIVES: To evaluate the psychopathological profile and the incidence of major
      depressive disorders in consecutive women attending a Menopause Clinic. METHODS:
      Women attending outpatient menopause clinic at Filippo del Ponte Hospital in
      Varese (Italy), referring to the centre from 1 March to 30 April 2005, were
      invited to fill up a specific questionnaire while waiting for the visit. The
      questionnaire included demographics and history (e.g. current or past use of
      antidepressant drugs); symptoms check list (SCL-90-R); Beck depression inventory
      (BDI). RESULTS: Sixty-four women were enrolled to the study. On the SCL-90-R,
      "somatic" symptoms cluster was the most frequent. Patients diagnosed as depressed
      using the Beck depression inventory (BDI) were 18 (28.1%). Thirteen (70%) of
      currently depressed women presented a positive history of depressive disorders.
      The analysis of depressed women according to previous depressive disorders
      revealed higher scores for women with positive history in both scales. Depressed
      patients have a significantly lower mean age compared to non-depressed patients
      (53.3+/-6.2 years versus 57.33+/-4.9 years, p=0.023). CONCLUSIONS: Our
      preliminary data show a high correlation between a history of depressive disorder
      and recurrence of depression in the menopausal period. Perimenopause seems to be
      a higher risk period for the development of a depressive disease compared to
      menopausal status. The somatization cluster warrants further investigation.

PMID- 16963206
TI  - Qualities and attributes desired in menopause clinicians.
AB  - OBJECTIVE: To assess the qualities and attributes desired in menopause
      clinicians. DESIGN: Women > or =45 years of age (n=72) were surveyed about the
      qualities and attributes desired in their physician. Surveys were performed in
      physician waiting rooms in Connecticut. RESULTS: Although fewer men are entering
      the practice of ObGyn, more than 88% of peri- and post-menopausal women believe
      that gender does not affect the quality of their women's health provider. Among
      the 68 women from whom valid data were obtained, experience (95.6%), knowledge
      (95.6%), and ability (92.6%) were the most important qualities. Only 4.2% listed
      gender in the top three most important qualities. If the patient's visit was for
      wellness- and screening-related issues, 6.6% (n=4) preferred a male, 13.1% (n=8)
      preferred a female, and 80.3% (n=49) had no preference for gender. The percentage
      of patients preferring to see a female was slightly higher (29.2%) if the visit
      was for a pelvic exam, while the percentage preferring to see a male (14.5%) was
      greater if care involved gynecological surgery. CONCLUSIONS: As medical practices
      meet the increasing demand of menopausal women, it is helpful to know the
      qualities and attributes that patients desire. Menopause clinicians should seek
      to convey experience, knowledge, and competence to their patients. A menopause
      practice should strive for a well-diversified team that will bring these
      qualities to menopausal patients. Given the shifting balance of male and female
      ObGyn providers, when hiring providers or establishing a menopause clinic, it is
      helpful to know that gender diversification is of minor importance.

PMID- 16963207
TI  - Platelet adsorption and hemolytic properties of liquid crystal/composite
      polymers.
AB  - The aim of this study is to investigate how the presence of liquid crystal,
      cholesteryl oleyl carbonate, embedded into polymers (PMMA, Eb270, PU) affects the
      biocompatibility of composite membranes with human blood. The effects of
      different surface textures of composite membranes on platelet adhesion and
      platelet activation were evaluated as well. The adhesion and geometric
      deformation of platelets were demonstrated by SEM. The quantitative assay of
      platelet activation was determined by measuring the production of P-Selectin, and
      by measurement of the blood clotting index when PRP blood was incubated with pure
      polymer films and composite membranes. Moreover, the hemolysis studies on the
      damage to red blood cells were performed to gain information on the
      hemocompatibility of these biomaterials. The results showed that inclusion of
      cholesteryl oleyl carbonate (COC) embedded in composite membranes, improves their
      biocompatibility with respect to a substantial reduction of platelet adhesion and
      the controlled decrease of platelet activation. As the COC content of composite
      membranes was increased, the value of the blood clotting index increased and the
      production of P-Selectin decreased. The results also showed that the presence of
      COC resulted in a decrease of hemolysis ratios. Comparing among three different
      composite membranes, the best biocompatibility is achieved when PU/COC> or
      ==Eb270/COC>PMMA/COC. The in vitro studies performed in this work suggest that it
      may be reasonable to use liquid crystal COC as a mean of surface modification to
      improve the blood compatibility of biopolymers.

PMID- 16963208
TI  - Release characteristics of anionic drug compounds from liquid crystalline gels
      III. Chemical and iontophoretic enhancement of delivery across non-rate-limiting
      membranes.
AB  - This paper investigates the release and transport of a range of anionic drugs
      from liquid crystalline gels using chemical and physical enhancement techniques.
      Previous papers [Fitzpatrick, D., Corish, J., 2005. Release characteristics of
      anionic drug compounds from liquid crystalline gels. I. Passive release across
      non-rate limiting membranes. Int. J. Pharm. 301, 226-236; Fitzpatrick, D.,
      Corish, J., 2006. Release characteristics of anionic drug compounds from liquid
      crystalline gels. II. The effects of ion pairing and buffering on the passive
      delivery of anionic drugs across non rate-limiting membranes. Int. J. Pharm.]
      have reported on the passive release profiles and those resulting from the
      incorporation of a chemical enhancer in the vehicle. This paper investigates the
      behaviour of the system under iontophoretic conditions and also under those of
      combined physical and chemical enhancement. The data presented here are directly
      comparable to previous work by Nolan et al. [; Nolan, L.M.A., Corish, J.,
      Corrigan, O.I., Fitzpatrick, D., 2006. Combined effects of iontophoretic and
      chemical enhancement on drug delivery. II. Transport across human and hairless
      murine skin. Int. J. Pharm., submitted for publication] which investigated the
      behaviour of cationic compounds under analogous conditions. The iontophoretic
      release of diclofenac in the presence of model enhancers is thoroughly
      investigated. It is also shown that a range of anionic drug molecules undergo an
      electrochemical change during the course of the experiments which leads to their
      poor detection. This may be a factor in the under reporting of iontophoretic
      delivery of anionic drugs in the literature. However, it has been shown that the
      transport of the drugs is greatly enhanced by the application of an iontophoretic
      current. Results of combined enhancement studies provide a positive basis on
      which to proceed with in vitro studies of the system across human skin.

PMID- 16963209
TI  - Cortical processing of quasi-periodic versus random noise sounds.
AB  - The first objective was to confirm using auditory evoked potentials (AEPs) the
      findings of magnetoencephalographic studies, that quasi-periodic iterated rippled
      noise (IRN) elicits a population response in the human auditory cortex which is
      topographically distinct from that elicited by random noise with a similar
      overall frequency spectrum. AEPs were recorded at the onset of random noise from
      silence, at the transition from random noise to IRN with a period of 5 ms, and in
      the two complementary conditions, IRN onset from silence and the transition from
      IRN to random noise. An N1/P2 complex was recorded to all four stimuli, that to
      the transition to IRN being significantly the most anteriorly distributed on the
      scalp. The second objective was to determine whether the response to the
      transition to IRN was due to detection of its quasi-periodicity, rather than its
      spectral "ripples". Virtually no effect was found of applying a 2 kHz low- or
      high-pass filter, above which it is unlikely that the spectral ripples at
      intervals of 200 Hz would have been resolved on the cochlear partition. It is
      concluded that a substantial neuronal population in the auditory cortex is
      influenced by temporal regularity in sounds, and that this population is equally
      responsive to spectral frequencies below and above 2 kHz.

PMID- 16963210
TI  - Plants popularly used for loosing weight purposes in Porto Alegre, South Brazil.
AB  - In this study, 14 herbalists (herb sellers) were interviewed about popular use of
      plants with weight loss purpose in Porto Alegre, a South Brazil city. For all
      identified species, scientific data were reviewed aiming to establish a
      correlation between popular use and biological properties. Seventy-eight samples
      were reported as having weigh loss properties. These samples come from 23 species
      and Asteraceae encompasses the greatest number of representatives. The greatest
      number of herbalist's citations was Baccharis articulata. The majority of plants
      have traditional use in Brazil but none is explicitly cited for loosing weight
      purposes. The pharmacological data are mainly from animal and in vitro studies
      and do not straight related to obesity. Only Ilex paraguariensis presents
      clinical data of efficacy in the treatment of obesity. Seven species present pre
      clinical data that indicate a potential role in the control of certain conditions
      which are associated with obesity, such as hyperlipidemia (Campomanesia
      xanthocarpa, Cuphea carthagenensis, Cynara scolymus, Hibiscus sabdariffa, Ilex
      paraguariensis) and high levels of blood glucose (Achyrocline satureioides,
      Baccharis trimera, Campomanesia xanthocarpa). In conclusion, scientific data
      found are insufficient to guarantee the efficacy and safety of these plants for
      treating obesity. However, some of them present activities which could be useful
      to treat certain obesity comorbidities and deserve further studies.

PMID- 16963211
TI  - Preliminary pharmacological screening of Bixa orellana L. leaves.
AB  - Preliminary pharmacological studies were performed on the methanol extract of
      Bixa orellana L. (Bixaceae) leaves to investigate neuropharmacological,
      anticonvulsant, analgesic, antidiarrhoeal activity and effect on gastrointestinal
      motility. All studies were conducted in mice using doses of 125, 250 and 500
      mg/kg of body weight. In the pentobarbitone-induced hypnosis test, the extract
      statistically reduced the time for the onset of sleep at 500 mg/kg dose and (dose
      dependently) increased the total sleeping time at 250 and 500 mg/kg dose. A
      statistically significant decrease in locomotor activity was observed at all
      doses in the open-field and hole-cross tests. In the strychnine-induced
      anticonvulsant test, the extract increased the average survival time of the test
      animals (statistically significant at 250 and 500 mg/kg). The extract
      significantly and dose-dependently reduced the writhing reflex in the acetic acid
      induced writhing test. Antidiarrhoeal activity was supported by a statistically
      significant decrease in the total number of stools (including wet stools) in
      castor oil-induced diarrhoea model. A statistically significant delay in the
      passage of charcoal meal was observed at 500 mg/kg in the gastrointestinal
      motility test. The extract was further evaluated in vitro for antioxidant and
      antibacterial activity. It revealed radical scavenging properties in the DPPH
      assay (IC(50)=22.36 microg/ml) and antibacterial activity against selected
      causative agents of diarrhoea and dysentery, including Shigella dysenteriae.

PMID- 16963212
TI  - Lunacridine from Lunasia amara is a DNA intercalating topoisomerase II inhibitor.
AB  - An ethnobotanical survey of plants used to treat tropical ulcers in Papua New
      Guinea identified Lunasia amara as possessing anti-Staphylococcus aureus
      activity. Activity-guided fractionation of the aqueous bark extract resulted in
      the identification of the quinoline alkaloid lunacridine as the active principle.
      Lunacridine tends to cyslise at room temperature but the 2'-O-trifluoroacetyl
      derivative was found to be stable and therefore more suitable for biological
      assays. The compound exhibited a minimal inhibitory concentration (MIC) of 64
      micro g/ml against Staphylococcus aureus NCTC 6571 and activity in the low
      micromolar range against HeLa and H226 cells; the latter showing signs of caspase
      3/7 mediated apoptotic cell death. Experiments with drug resistant strains of
      Streptococcus pneumoniae suggested topoisomerase as a likely target for the drug
      in bacteria whilst decatenation assays with human topoisomerase II showed the
      compound to be a potent inhibitor of this isoform (IC(50)<5 micro M) thus
      explaining the drug's activity against human cell lines. Both lunacridine and 2'
      O-trifluoroacetyl lunacridine exhibited mild DNA intercalation activity giving
      50% decrease in ethidium DNA fluorescence at 0.22 and 0.6 mM, respectively,
      placing the drug amongst the DNA intercalating class of topoisomerase II
      inhibitors.

PMID- 16963213
TI  - Immuno-enhancement effects of Huang Qi Liu Yi Tang in a murine model of
      cyclophosphamide-induced leucopenia.
AB  - Tonic Chinese prescriptions are widely used in daily foods to improve health in
      Taiwan. Huang Qi Liu Yi Tang (HQLYT) is one such tonic Chinese prescription. In
      this study, the immuno-enhancement effects of HQLYT tonic were explored using an
      in vitro splenocyte proliferation assay and by evaluating improvements in
      cyclophosphamide-induced leucopenia in a BaLb/c mice model. HQLYT is composed of
      Radix Astragali, licorice, and jujube, and extracted in boiling water. The
      contents of glycyrrhizin and formononetin were used as bioactive markers to
      control the quality of the HQLYT water extract, at 7.26+/-0.04mg/g and 112.07+/
      0.08 micro g/g, respectively. In the in vitro assay, HQLYT (12.5 micro g/ml)
      showed better immuno-enhancing effects than Radix Astragali, licorice, or jujube
      alone, and enhanced the survival rate of splenocytes by 88%. Moreover, HQLYT
      significantly enhanced the cytotoxic effects of natural killer cells of
      splenocytes against YAC-1 cells. The BaLb/c mice were fed HQLYT once a day for 14
      days. After oral treatment with HQLYT 400mg/kg body weight (BW), the IL-2 release
      in BaLb/c mice and the natural killer cell activity of the splenocytes were both
      enhanced, and the WBC level of cyclophosphamide-induced leucopenic mice was
      improved by treatment with 400mg HQLYT/kgBW. HQLYT significantly delayed the
      decline in the WBC level and affected a faster recovery of the WBC level back to
      a normal status. In summary, HQLYT enhanced immunologic functions in both in
      vitro and in vivo studies. These results offer scientific evidence to prove the
      efficacy of this tonic Chinese prescription.

PMID- 16963214
TI  - The efficacy of herbal medicines in clinical models: the case of jambolan.
AB  - A large proportion of drugs employed in clinical practice come from plants. The
      development of new medical agents is a lengthy and time-consuming process, with
      the identification of extracts with putative therapeutic effects, the isolation
      of active ingredients and pre-clinical studies to investigate their
      pharmacological profile. We propose a shortcut in this sequence of procedures,
      testing first if the extracts, in the way they are used by patients, have
      efficacy in clinical models. On the one hand, this allows to screen plants with
      higher chances to identify novel drug candidates; this method may result in
      information with immediate interest for patients who take these traditional
      preparations, informing them about efficacy, inertia and risks of the product. In
      this commentary, we describe our own experience applying this approach to
      investigate the potential antihyperglycemic effect of tea and extracts prepared
      from leaves of jambolan (Syzygium cumini and Syzygium jambos). The experiments
      with normal rats, rats with streptozotocin-induced diabetes, normal volunteers
      and patients with diabetes were all negative in regard to an antihyperglycemic
      effect of this plant. In view of the pharmacological inertia of jambolan in the
      clinical model, patients and physicians should not rely on its putative
      antihyperglycemic effect. This approach may also be applicable to other popular
      medicines employed in the management of diabetes and other diseases.

PMID- 16963215
TI  - Cannabinoid concentrations in hair from documented cannabis users.
AB  - Fifty-three head hair specimens were collected from 38 males with a history of
      cannabis use documented by questionnaire, urinalysis and controlled, double blind
      administration of delta9-tetrahydrocannabinol (THC) in an institutional review
      board approved protocol. The subjects completed a questionnaire indicating daily
      cannabis use (N=18) or non-daily use, i.e. one to five cannabis cigarettes per
      week (N=20). Drug use was also documented by a positive cannabinoid urinalysis, a
      hair specimen was collected from each subject and they were admitted to a closed
      research unit. Additional hair specimens were collected following smoking of two
      2.7% THC cigarettes (N=13) or multiple oral doses totaling 116 mg THC (N=2).
      Cannabinoid concentrations in all hair specimens were determined by ELISA and
      GCMSMS. Pre- and post-dose detection rates did not differ statistically,
      therefore, all 53 specimens were considered as one group for further comparisons.
      Nineteen specimens (36%) had no detectable THC or 11-nor-9-carboxy-THC (THCCOOH)
      at the GCMSMS limits of quantification (LOQ) of 1.0 and 0.1 pg/mg hair,
      respectively. Two specimens (3.8%) had measurable THC only, 14 (26%) THCCOOH
      only, and 18 (34%) both cannabinoids. Detection rates were significantly
      different (p<0.05, Fishers' exact test) between daily cannabis users (85%) and
      non-daily users (52%). There was no difference in detection rates between African
      American and Caucasian subjects (p>0.3, Fisher's exact test). For specimens with
      detectable cannabinoids, concentrations ranged from 3.4 to >100 pg THC/mg and
      0.10 to 7.3 pg THCCOOH/mg hair. THC and THCCOOH concentrations were positively
      correlated (r=0.38, p<0.01, Pearson's product moment correlation). Using an
      immunoassay cutoff concentration of 5 pg THC equiv./mg hair, 83% of specimens
      that screened positive were confirmed by GCMSMS at a cutoff concentration of 0.1
      pg THCCOOH/mg hair.

PMID- 16963216
TI  - The ecology and biodemography of Caenorhabditis elegans.
AB  - The nematode Caenorhabditis elegans is a well-known model organism for research
      on aging and life span, but very little is known about its ecology and natural
      history. The strain N2 is the standard wild-type C. elegans and arose from the
      progeny of a single hermaphrodite. Since N2 has passed through laboratory
      culture, the influence of inadvertent selection and genetic drift on C. elegans
      strains kept in culture is unclear. Because it seems that other wild-type strains
      have also been subject to lengthy laboratory culture, the life span and
      biodemography of wild-caught C. elegans is of interest. We recovered C. elegans
      from snails (Helix aspersa) in ca. 50% of the California locations where we made
      collections. In experiments with one of the wild-caught isolates, it differed in
      important demographic properties, mortality, fertility, fitness, and activity
      patterns, from the standard N2 strain, when both strains were evaluated in a
      common laboratory environment. The differences were not only statistically
      significant; they were also large enough to be biologically important. The
      differences are consistent with the hypothesis that N2 has adapted to laboratory
      conditions.

PMID- 16963217
TI  - Control of Caenorhabditis elegans life history by nuclear receptor signal
      transduction.
AB  - Caenorhabditis elegans diapause, reproductive development, and life span are
      influenced by the DAF-12 nuclear hormone receptor signaling pathway. Here, we
      describe how this nuclear receptor integrates environmental and physiologic cues
      and regulates developmental age, reproduction and aging.

PMID- 16963218
TI  - MR imaging features of pure mucinous carcinoma of the breast.
AB  - OBJECTIVE: To characterize MR imaging features of pure mucinous carcinoma of the
      breast. MATERIALS AND METHODS: MR images obtained from 16 women (age range, 29
      81; mean age, 57 years) with pure mucinous carcinoma of the breast determined at
      surgery were reviewed. The MR findings used were shape, margin, internal mass
      enhancement, kinetic curve pattern on dynamic study, signal intensity on short
      time inversion recovery (STIR) T2-weighted images, and non-mass-like enhancement
      around the main tumor. Non-mass-like enhancement was compared with the presence
      of extensive intraductal component (EIC) on histopathological findings. RESULTS:
      Eleven tumors (69%) had lobular contour, and nine tumors (56%) had smooth margin.
      Eight tumors (50%) showed rim enhancement and six tumors (38%) showed
      heterogeneous enhancement. Fourteen tumors (88%) showed a persistent enhancing
      pattern on kinetic curve. Fifteen tumors exhibited homogenous strongly high
      signal intensity on STIR T2-weighted images. In six cases with EIC, five cases
      had non-mass-like enhancement around the main mass. CONCLUSIONS: MR findings such
      as lobular shape, rim or heterogeneous enhancement, persistent pattern on kinetic
      curve, and homogeneous strongly high signal intensity on STIR T2-weighted images
      may be useful in diagnosing pure mucinous carcinoma. Moreover, linear-ductal
      enhancement around main mass may indicate presence of EIC.

PMID- 16963219
TI  - Cost analysis in interventional radiology--A tool to optimize management costs.
AB  - OBJECTIVE: The objective of the study was to analyze the methods to reduce cost
      in interventional radiology departments by reorganizing procurement. MATERIALS
      AND METHODS: All products used in the Department of Interventional Radiology were
      inventoried. An ABC-analysis was completed and A-products (high-value and high
      turnover products) underwent a XYZ-analysis which predicted demand on the basis
      of ordering frequency. Then criteria for a procurement strategy for the different
      material categories were fixed. The net working capital (NWC) was calculated
      using an interest rate of 8%/year. RESULTS: Total annual material turnover was
      353,000 euro. The value of all A-products determined by the inventory was 260,000
      euro. Changes in the A-product procurement strategy tapped a cost reduction
      potential of 14,500/year euro. The resulting total saving was 17,200 euro.
      Improved stores management added another 37,500 euro. The total cost cut of
      52,000 euro is equivalent to 14.7% of annual expenses. CONCLUSION: A flexible
      procurement strategy helps to reduce the storage and capital tie-up costs of A
      products in interventional radiology without affecting the quality of service
      provided to patients.

PMID- 16963220
TI  - Ganglionary mechanisms of spasticity and ileus in cerebral hemorrhage: an
      experimental study.
AB  - OBJECTIVE: The effects of retrograde neuronal death is well determined in dorsal
      root ganglia (DRG) after peripheral nerve injury, but the effects of
      intracerebral hemorrhage on the DRG has not been well known. In this study, it
      was investigated if hemorrhagic lesions of sensory-motor cortex cause
      neurodegeneration on DRG. MATERIALS AND METHODS: This study was conducted on 23
      male hybrid rabbits. Three of 23 animals were examined as control. Left parietal
      burr-hole surgery was applied to remaining 20 animals and autolog blood of 0.25ml
      injected into left sensory-motor region under general anesthesia. All rabbits
      were followed-up for two months and sacrificed. L(5) DRG's were observed
      histopathologically. The results were analyzed with Mann-Whitney U-test. RESULTS:
      Right spastic hemiplegia developed only in 16 operated animals and 10 of them
      were developed ileus. The number of degenerated neurons in DRG was higher in the
      plegic side than in the non-plegic side (p<0.001). But, the difference between
      the non-plegic side of the study group and control group did not meaningful
      (p>0.05). CONCLUSION: Intracerebral hemorrhages affecting the sensory-motor
      cortex may result in neurodegeneration in DRG. Sensitive reflex arches of
      striated muscles and bowels may be disturbed due to DRG degeneration and results
      in spasticity and/or ileus.

PMID- 16963221
TI  - Interpretation biases in victims and non-victims of interpersonal trauma and
      their relation to symptom development.
AB  - Previous studies examining information processing in posttraumatic stress
      disorder (PTSD) have focused on attention and memory biases, with few studies
      examining interpretive biases. The majority of these studies have employed
      lexically based methodologies, rather than examining the processing of visual
      information. In the present study, victims (N=40) and non-victims (N=41) of
      interpersonal trauma viewed a series of short positive, neutral, and threatening
      filmstrips of social situations with ambiguous endings. Participants were then
      asked about their perceptions and interpretations of the situations. Victims
      perceived threatening situations as more predictable and more quickly increasing
      in risk than non-victims. Trauma status interacted with the perceived
      predictability of positive situations and the perceived speed with which neutral
      situations reached their conclusion to predict anxious symptoms. In addition,
      trauma status interacted with the perceived increase in risk of positive
      situations to predict PTSD symptoms. The implications of these findings for
      theories of PTSD are discussed.

PMID- 16963222
TI  - Defective splicing of Megf7/Lrp4, a regulator of distal limb development, in
      autosomal recessive mulefoot disease.
AB  - Mulefoot disease (MFD) is an autosomal recessive disorder of phenotypically
      variable expression that causes syndactyly in certain strains of cows. MFD maps
      to a narrow interval on bovine chromosome 15 that is syntenic to human chromosome
      11p12-p11.2. This region contains MEGF7/LRP4 (approved gene symbol LRP4), a gene
      that encodes a member of the multifunctional low-density lipoprotein receptor
      gene family. Targeted and naturally occurring mutations in the murine Megf7/Lrp4
      gene, a putative coreceptor in the Wnt signaling pathway, cause polysyndactyly in
      the rodent. Thus, Megf7/Lrp4 is a strong candidate for the MFD mutation. Using
      PCR analysis of tissue samples and sperm from confirmed homozygous MFD carriers,
      we have identified a functional single base pair mutation in the affected
      animals. We show that a G --> A transition at the first nucleotide in the splice
      donor site of intron 37 completely disables this splice site. The abnormal
      splicing that is caused by this mutation predicts the generation of a
      dysfunctional membrane-anchored receptor lacking the normal cytoplasmic domain.
      These findings confirm that autosomal recessive loss-of-function mutations in
      Megf7/Lrp4 result in phenotypically similar forms of syndactyly in different
      mammalian species and that such mutations are the cause of MFD in bovines.

PMID- 16963223
TI  - Development of an internally controlled, homogeneous polymerase chain reaction
      assay for the simultaneous detection and discrimination of herpes simplex virus
      types 1 and 2 and varicella-zoster virus.
AB  - Homogeneous polymerase chain reaction (PCR) technology is being used increasingly
      in the diagnosis of infectious disease. The sensitivity and specificity of PCR is
      being coupled to the ease-of-use and multiplexing capacity of homogeneous
      methodologies to provide rapid and accurate differential diagnoses. This
      technology is applicable to the diagnosis of infections with the human herpes
      viruses, herpes simplex virus 1 (HSV 1), HSV 2 and varicella-zoster virus (VZV).
      Our aim was to develop and evaluate a homogeneous PCR assay which combines the
      following features: the assay can detect and distinguish HSV types 1 and 2 and
      VZV, can be performed on untreated clinical samples, contains internal control
      reagents to monitor for inhibitors in the sample and allows automatic assignment
      of viral genotypes. Primers and probes specific for HSV and VZV genes were
      combined and optimized in a multiplex PCR. An internal control was designed which
      allowed use of the VZV primers and a human factor V gene DNA template. The assay
      was evaluated on an initial cohort of 66 clinical swab samples, with results
      determined by visual inspection of melt curves. Parameters obtained from this
      study were used to assign genotypes automatically to a second group of 85
      clinical swab samples. Optimization of reagents produced melt curve peaks of
      sufficient height and symmetry for automatic genotype assignment. In the initial
      cohort of 66 samples, 63 returned concordant results, one sample produced an
      aberrant peak due to sequence variation and the remaining two samples were
      positive on re-test. Automatic genotype assignment of the second group of 85
      samples resulted in correct identification of 79 samples, with two further
      aberrant peaks, and two samples positive on retest. The development of this assay
      should facilitate the rapid detection of herpes viruses from clinical swab
      samples.

PMID- 16963224
TI  - PKC delta phosphorylates p52ShcA at Ser29 to regulate ERK activation in response
      to H2O2.
AB  - Both PKC delta and ShcA have been implicated in cell response to oxidative stress
      [Y. Hu, X. Wang, L. Zeng, D.Y. Cai, K. Sabapathy, S.P. Goff, E.J. Firpo, B. Li,
      Mol Biol Cell., 16 (2005) 3705-3718, B. Li, X. Wang, N. Rasheed, Y. Hu, S. Boast,
      T. Ishii, K. Nakayama, K.I. Nakayama, S.P., Goff, Genes Dev, 18 (2004) 1824-1837,
      E. Migliaccio, M. Giorgio, S. Mele, G. Pelicci, P. Reboldi, P.P. Pandolfi, L.
      Lanfrancone, P.G. Pelicci, Nature, 402 (1999) 309-313], yet their relationship in
      the response has not been studied. Here we report that PKC delta interacts with
      ShcA and this interaction is promoted by H(2)O(2). PKC delta and ShcA are also
      colocalized in the cytoplasm and displayed co-translocation in response to
      H(2)O(2). Activated PKC delta was able to phosphorylate ShcA at Ser29, as
      determined by mass spectrometry. These results suggest that ShcA, p66 and p52,
      are substrates that interact with PKC delta. This phosphorylation is critical in
      H(2)O(2) induced ERK activation as reconstitution with ShcA Ser29A failed to
      rescue ERK activation of ShcA-/- MEFs, while ShcA could. In line with this
      conclusion, inhibition of PKC delta with inhibitors is able to diminish H(2)O(2)
      induced ERK activation in MEFs. These results suggest that the interaction
      between PKC delta and ShcA and the phosphorylation of ShcA at Ser29 play
      important roles in ERK activation in cell response to H(2)O(2).

PMID- 16963225
TI  - Ceramide/sphingosine/sphingosine 1-phosphate metabolism on the cell surface and
      in the extracellular space.
AB  - Sphingolipid metabolites, ceramide, sphingosine, and sphingosine 1-phosphate,
      have emerged as a new class of lipid biomodulators of various cell functions.
      These metabolites are known to function not only as intracellular second
      messengers, but also in the extracellular space. Sphingosine 1-phosphate
      especially has numerous functions as an important extracellular mediator that
      binds to cell surface S1P receptors. Recent studies have also shown that
      sphingolipid-metabolizing enzymes function not only in intracellular organelles
      but also in the extracellular spaces, including the outer leaflet of the plasma
      membrane. This review focuses on the metabolic enzymes (acid and alkaline
      sphingomyelinases, neutral ceramidase, and sphingosine kinase) that are involved
      in the production of the sphingolipid metabolites in these extracellular spaces,
      and on the metabolic pathway itself.

PMID- 16963226
TI  - PKCalpha regulates phosphorylation and enzymatic activity of cPLA2 in vitro and
      in activated human monocytes.
AB  - Phospholipases A(2) (PLA(2)) are potent regulators of the inflammatory response.
      We have observed that Group IV cPLA(2) activity is required for the production of
      superoxide anion (O(2)(-)) in human monocytes [Li Q., Cathcart M.K. J. Biol.
      Chem. 272 (4) (1997) 2404-2411.]. We have previously identified PKCalpha as a
      kinase pathway required for monocyte O(2)(-) production [Li Q., Cathcart M.K. J.
      Biol. Chem. 269 (26) (1994) 17508-17515.]. We therefore investigated the
      potential interaction between PKCalpha and cPLA(2) by evaluating the requirement
      for specific PKC isoenzymes in the process of activating cPLA(2) enzymatic
      activity and protein phosphorylation upon monocyte activation. We first showed
      that general PKC inhibitors and antisense oligodeoxyribonucleotides (ODN) to the
      cPKC group of PKC enzymes inhibited cPLA(2) activity. To distinguish between
      PKCalpha and PKCbeta isoenzymes in regulating cPLA(2) protein phosphorylation and
      enzymatic activity, we employed our previously characterized PKCalpha or PKCbeta
      isoenzyme-specific antisense ODN [Li Q., Subbulakshmi V., Fields A.P., Murray,
      N.R., Cathcart M.K., J. Biol. Chem. 274 (6) (1999) 3764-3771]. Suppression of
      PKCalpha expression, but not PKCbeta expression, inhibited cPLA(2) protein
      phosphorylation and enzymatic activity. Additional studies ruled out a
      contribution by Erk1/2 to cPLA(2) phosphorylation and activation. We also found
      that cPLA(2) co-immunoprecipitated with PKCalpha and vice versa. In vitro studies
      demonstrated that PKCalpha could directly phosphorylate cPLA(2).and enhance
      enzymatic activity. Finally, we showed that addition of arachidonic acid restored
      the production of O(2)(-) in monocytes defective in either PKCalpha or cPLA(2)
      expression. Taken together, our data suggest that PKCalpha, but not PKCbeta, is
      the predominant cPKC isoenzyme required for cPLA(2) protein phosphorylation and
      maximal induction of cPLA(2) enzymatic activity upon activation of human
      monocytes. Our data also support the concept that the requirements for PKCalpha
      and cPLA(2) in O(2)(-) generation are solely due to their seminal role in
      generating arachidonic acid.

PMID- 16963227
TI  - Hydrogen peroxide impairs GRK2 translation via a calpain-dependent and cdk1
      mediated pathway.
AB  - Oxidative mechanisms of injury are involved in many neurodegenerative diseases
      such as stroke, ischemia-reperfusion injury and multiple sclerosis. G protein
      coupled receptor kinase 2 (GRK2) plays a key role in G protein-coupled receptor
      (GPCR) signaling modulation, and its expression levels are decreased after brain
      hypoxia/ischemia and reperfusion as well as in several inflammatory conditions.
      We report here that hydrogen peroxide downregulates GRK2 expression in C6 rat
      glioma cells. The hydrogen peroxide-induced decrease in GRK2 is prevented by a
      calpain protease inhibitor, but does not involve increased GRK2 degradation or
      changes in GRK2 mRNA level. Instead we show that hydrogen peroxide treatment
      impairs GRK2 translation in a process that requires Cdk1 activation and involves
      the mTOR pathway. This novel mechanism for the control of GRK2 expression in
      glial cells upon oxidative stress challenge may contribute to the modulation of
      GPCR signaling in different pathological conditions.

PMID- 16963228
TI  - Tribbles: a family of kinase-like proteins with potent signalling regulatory
      function.
AB  - The recent identification of tribbles as regulators of signal processing systems
      and physiological processes, including development, together with their potential
      involvement in diabetes and cancer, has generated considerable interest in these
      proteins. Tribbles have been reported to regulate activation of a number of
      intracellular signalling pathways with roles extending from mitosis and cell
      activation to apoptosis and modulation of gene expression. The current review
      summarises our current understanding of interactions between tribbles and various
      other proteins. Since our understanding on the molecular basis of tribbles
      function is far from complete, we also describe a bioinformatic analysis of
      various segments of tribbles proteins, which has revealed a number of highly
      conserved peptide motifs with potentially important functional roles.

PMID- 16963229
TI  - Amisulpride-induced tardive dyskinesia.
AB  - Tardive dyskinesia (TD) is a movement disorder that develops during the course of
      long-term treatment with neuroleptic agents and is characterized primarily by
      choreiform and athetotic movements. We report the case of a 34-year-old man
      suffering from schizophrenia, disorganized type. He received amisulpride (400 mg
      daily) and the result was much improvement. 20 months later, he was presented
      with TD, which resolved almost completely after change of treatment to 1200 mg
      quetiapine without any relapsing. To our knowledge, his is the first case report
      in the literature of tardive dyskinesia induced by amisulpride.

PMID- 16963230
TI  - Identification of translational release factor eRF1a binding sites on eRF3 in
      Euplotes octocarinatus.
AB  - Translation termination in eukaryotes is mediated by two polypeptide chain
      release factors, eRF1 and eRF3. eRF1 recognizes stop signals, while eRF3 is a
      ribosome-dependent and eRF1-dependent GTPase. eRF1 forms a stable complex with
      eRF3 in vivo and in vitro. In the present study, a variety of truncated forms of
      Euplotes octocarinatus eRF3 were created, and systematic analysis of the
      interaction between E. octocarinatus eRF1a and these eRF3 mutants was performed
      by employing both in vivo a yeast two-hybrid assay and in vitro a pull-down
      assay. The results demonstrated that a short portion of the C-terminal domain of
      eRF3 is sufficient for eRF1a binding in E. octocarinatus. Specifically, the eRF1a
      binding sites on eRF3 are located at a region containing amino acid residues 640
      723 in E. octocarinatus eRF3. Amino acid sequence analysis of eRF3 from E.
      octocarinatus, humans and yeast showed that the eRF1a binding domain on E.
      octocarinatus eRF3 was similar to that of yeast eRF3 but different from that of
      human eRF3.

PMID- 16963231
TI  - Sigma X induces competence gene expression in Streptococcus pyogenes.
AB  - Although not thought to become competent for DNA uptake, the bacterium
      Streptococcus pyogenes appears to encode within its genome the DNA uptake and
      recombination machinery required for competence. The promoters of these genes
      contain a conserved sequence, CIN-box, which is recognized by the S. pyogenes
      alternative RNA polymerase sigma factor X. Using microarray technology, we found
      that sigma X induced the expression of competence genes in S. pyogenes. Real-time
      RT-PCR was performed to confirm that the expression of these transcripts was
      induced 2-265-fold by sigma X. Of the eight CIN-box loci induced, femB, the
      ortholog a virulence factor in Staphylococcus aureus, was shown to be transcribed
      in vitro by RNA polymerase containing sigma X, indicating that sigma X directly
      activates expression of this CIN-box gene. Sigma X-dependent induction of genes
      encoding competence machinery in S. pyogenes raises the possibility that some
      strains of this human pathogen can develop competence for genetic transformation.

PMID- 16963232
TI  - Mechanisms of daptomycin resistance in Staphylococcus aureus.
AB  - Daptomycin resistance in Staphylococcus aureus emerged during therapy of
      tricuspid endocarditis. Susceptibility to daptomycin of the parent strain (SA
      675), other daptomycin-susceptible strains and the non-susceptible mutant (SA
      684) was heterogeneous; however, subpopulations growing at concentrations above
      the minimum inhibitory concentration (MIC) were not stably resistant. Stable
      resistance was produced only by serial passage on daptomycin-containing media.
      Daptomycin dissipated the membrane potential of SA-675 but not SA-684, which also
      lost an 81 kDa membrane protein. Whole cells and membranes of SA-684 bound a
      reduced amount of daptomycin. Reduced drug binding in SA-684 correlates with
      daptomycin resistance, possibly as a result of the loss of a membrane protein
      'chaperone' with which daptomycin interacts. Heterogeneity of daptomycin MICs in
      susceptible strains may be an important factor in the development of stable,
      clinically relevant resistance.

PMID- 16963233
TI  - Mouse salivary glands and human beta-defensin-2 as a study model for
      antimicrobial gene therapy: technical considerations.
AB  - Transduction of salivary glands with antimicrobial peptide genes has great
      potential for oral infection control. Our ultimate goal is to introduce
      antimicrobial peptide genes into salivary glands that secrete these peptides into
      saliva to control bacterial/fungal infection in the oral cavity. However, an
      animal study model to test this potential has not been established. Therefore, we
      determined to test (i) whether the potent antimicrobial peptide human beta
      defensin-2 (hBD-2) can be overexpressed in saliva after transduction of salivary
      glands and (ii) whether oral fungal infection can be developed in a NOD/SCID
      murine model. Lentiviral vector SIN18cPPTRhMLV bearing hBD-2 cDNA was introduced
      into SCID mouse submandibular glands via cannulation. Reverse transcription
      polymerase chain reaction (RT-PCR), immunohistochemistry or enzyme-linked
      immunosorbent assay (ELISA) were performed to detect hBD-2 expression in glands
      or in saliva. Candida albicans 613p was inoculated orally into SCID mice to
      establish oral candidiasis. Whilst expression of hBD-2 was detected in mouse
      salivary glands by RT-PCR and immunohistochemistry 1 day or 1 week following
      delivery of lentivirus, hBD-2 was not detected in saliva. There was recoverable
      C. albicans from the oral cavity and gastrointestinal tract 4 days to 4 weeks
      after infection, but there was no establishment of observable oral candidiasis in
      SCID mice under a stereomicroscope. Our data indicate that lentiviral vectors
      transduce mouse salivary glands, but not at a sufficient level to allow hBD-2
      detection in saliva. Other vectors for gene transduction and additional treatment
      of SCID mice to establish oral candidiasis are needed in order to utilise mouse
      salivary glands to test antimicrobial gene therapy.

PMID- 16963234
TI  - Colistin in the treatment of life-threatening infections.

PMID- 16963235
TI  - Zebrafish foxe3: roles in ocular lens morphogenesis through interaction with
      pitx3.
AB  - Foxe3 is a winged helix/forkhead domain transcription factor necessary for
      mammalian and amphibian lens development. Human FOXE3 mutations cause anterior
      segment dysgenesis and cataracts. The zebrafish foxe3 cDNA was PCR amplified from
      24 h post-fertilization (hpf) embryo cDNA. The zebrafish foxe3 gene consists of a
      single exon on chromosome 8 and encodes a 422 amino acid protein. This protein
      possesses 44% and 67% amino acid identity with the human FOXE3 and Xenopus FoxE4
      proteins, respectively. A polyclonal antiserum was generated against a bacterial
      fusion protein containing the Foxe3 carboxyl terminus. The purified antiserum
      detects zebrafish Foxe3 on immunoblots, in embryo wholemounts, and frozen tissue
      sections. The zebrafish Foxe3 protein is first detected in the lens at 31hpf and
      is restricted to the nucleated cell population, including the epithelial and
      elongating fiber cells. Knockdown of Foxe3 protein using an antisense morpholino
      results in small lenses with multilayered epithelial cells and fiber cell
      dysmorphogenesis. The morphants posses normal retinas, although retinal cell
      proteins, including rhodopsin, are abnormally expressed in the morphant lens
      tissue. Functional interactions between foxe3 and pitx3 during lens development
      were assessed by RT-PCR and comparison of Foxe3 and Pitx3 protein expression in
      both foxe3 and pitx3 morphants. Immunoblots and immunohistochemistry reveal Pitx3
      is expressed in the foxe3 morphant lens, while Pitx3 knockdown results in the
      elimination of Foxe3 expression. These data demonstrate that Foxe3 is necessary
      for lens development in zebrafish and that foxe3 lies genetically downstream of
      pitx3 in a zebrafish lens development pathway.

PMID- 16963236
TI  - Effect of electrolytes on the cloud point of chlorpromazine hydrochloride
      solutions.
AB  - Cloud point (CP) phenomenon occurring in amphiphilic drug chlorpromazine
      hydrochloride (CPZ) solutions with and without salts is reported herein. The CP
      of a 50mM CPZ solution (prepared in 10mM sodium phosphate, SP, buffer) was found
      to decrease with increasing pH, both in the absence as well as presence (50mM) of
      added salts (NaCl, NaBr, LiBr, KBr, tetra-n-butylammonium bromide). Whereas, at a
      fixed concentration of NaCl, the CP increased with increasing CPZ concentration,
      addition of increasing amounts of salts (NaF, NaCl, NaBr, LiCl, KCl) to 50 mM CPZ
      solution (at pH 6.7) caused continuous increase in CP. On the basis of these
      studies the binding-effect orders of counterions and co-ions have been deduced,
      respectively, as: Br(-) > Cl(-) > F(-) and Li+ >Na+ >K+. The similar trend of
      increasing CP with addition of increasing amounts of quaternary bromides
      (tetramethylammonium bromide, TMeAB; tetraethylammonium bromide, TEtAB; tetra-n
      propylammonium bromide, TPrAB; tetra-n-butylammonium bromide, TBuAB; tetra-n
      pentylammonium bromide, TPeAB) to 50 mM CPZ solutions (at pH 6.7) was found to be
      dependent upon the alkyl chain length of the particular salt. The overall
      behaviour has been discussed in terms of electrostatic interactions, micellar
      growth, and mixed micelle formation.

PMID- 16963237
TI  - Nystatin in Langmuir monolayers at the air/water interface.
AB  - The paper presents a thorough characteristics of Langmuir monolayers formed at
      the air/water interface by a polyene macrolide antibiotic-nystatin. The
      investigations are based on the analysis of pi/A isotherms recorded for
      monolayers formed by this antibiotic at different experimental conditions. A
      significant part of this work is devoted to the stability and relaxation
      phenomena. It has been found that nystatin forms at the air/water interface
      monolayers of the LE state. A plateau region, observed during the course of the
      isotherm compression, is suggested to be due to the orientational change of
      nystatin molecules from horizontal to vertical position. Quantitative analysis of
      the desorption of the monolayer material into bulk water indicates that the
      solubility of nystatin monolayers increases with surface pressure. At low surface
      pressures, the desorption of nystatin from a monolayer is controlled both by
      dissolution and by diffusion. However, at the plateau and in the post-plateau
      region, the desorption does not achieve a steady state and the monolayer is less
      stable than in the pre-plateau region. However, the presence of membrane lipids,
      even at a low mole fraction, considerably increases the stability of nystatin
      monolayers. This enables the application of the Langmuir monolayer technique to
      study nystatin in mixture with cellular membrane components, aiming at verifying
      its mode of action and the mechanism of toxicity.

PMID- 16963238
TI  - Involvement of nitrergic and opioidergic systems in the hypothermia induced by
      cholestasis in rats.
AB  - BACKGROUND AND AIM: Cholestatic animals display abnormal hypothalamic responses
      to pyrogenic stimuli and decreased febrile response to lipopolysaccharide. The
      present study was undertaken to determine if obstructive cholestasis was
      associated with abnormal thermoregulation under thermoneutral conditions.
      METHODS: Male Sprague-Dawley rats weighing 200-250g were randomly divided into 21
      groups. Three sets of seven groups were unoperated control, sham-operated and
      bile duct-ligated rats. The groups of unoperated control, sham-operated and bile
      duct-ligated rats were treated with daily administration of isotonic saline
      solution, N(omega)-nitro-l-arginine methyl ester (l-NAME) (3, 10, or 20mg/kg),
      naltrexone (10 or 20mg/kg) or aminoguanidine (150mg/kg). Body temperatures were
      measured before and 1, 3, 5 and 7 days after the surgery. RESULTS: Bile duct
      ligated rats had lower body temperature than sham-operated animals at 3 (P<0.001)
      and 5 (P<0.01) days after surgery. l-NAME, a non-selective inhibitor of nitric
      oxide synthase (NOS) (10, 20mg/kg, i.p.) or aminoguanidine, a selective iNOS
      inhibitor (150mg/kg, i.p.), completely reversed this hypothermia (P>0.05).
      Naltrexone, a non-selective opioid antagonist (20mg/kg, i.p.), also completely
      corrected this hypothermia (P>0.05). There was a drop in temperature in the first
      day after the surgery in sham and BDL groups compared to unoperated controls,
      which was significant in some groups demonstrating the effect of surgery and
      anesthetic drugs on the body temperature. CONCLUSIONS: Cholestatic rats show
      impaired thermoregulation suggesting the involvement of nitrergic and opioidergic
      systems.

PMID- 16963239
TI  - Reactive oxygen metabolites and anti-oxidative defenses in aspirin-induced
      gastric damage in rats: Gastroprotection by Vitamin E.
AB  - OBJECTIVE: It has been proposed that neutrophil infiltration and oxygen radicals
      may be the important prime events that lead to mucosal injury induced by aspirin.
      Vitamin E acts as a potent antioxidant, and is capable of scavenging free
      radicals. The aim of this study was to evaluate the oxygen metabolites and anti
      oxidative defenses in acute gastric damage induced by aspirin and to find the
      effects of Vitamin E. METHODS: Ninety-six Wistar rats were divided into four
      groups of 24 rats each as follows: (1) the control group; (2) the ASA group that
      received 300mg/kg of ASA; (3) the Vitamin E plus ASA group and (4) the Vitamin E
      group that received Vitamin E (75 units) alone. At 3, 6, 9 and 24h after the drug
      administration, six rats were randomly selected from each group and gastric
      mucosal injury, prostaglandin E2, and the activities of myeloperoxidase, xanthine
      oxidase, superoxide dismutase, glutathione peroxidase as well as glutathione
      level were measured and compared between the groups. RESULTS: Oral administration
      of ASA caused acute gastric erosions and an increase in myeloperoxidase activity.
      It also decreased prostaglandin E2, superoxide dismutase activity, glutathione
      peroxidase activity and glutathione level. Concomitant administration of Vitamin
      E and ASA restored all the changes toward the control levels. CONCLUSION: Free
      radicals and suppression of anti-oxidizing enzymes play important roles in
      gastric damage induced by aspirin. Increased myeloperoxidase activity suggests
      that activated neutrophils may be a major source of free radicals. Vitamin E
      protects against ASA-induced damage due to its anti-oxidizing activity.

PMID- 16963240
TI  - Correlation of electrocorticographic to clinical seizure onset and
      interhemispheric propagation times in temporal lobe epilepsy.
AB  - This study was performed to test the hypothesis that, in human temporal lobe
      epilepsy, electrocorticographic time factors involved in the ictal EEG to
      clinical ictal transition (electrocorticographic to clinical seizure onset time,
      ECOT) and the interhemispheric propagation of epileptic activity
      (interhemispheric propagation time, IHPT), which are independently correlated
      with temporal lobe epileptogenicity and predictive of seizure-free outcome
      following temporal lobectomy, are correlated with one another in a quantitative
      fashion. A series of 37 patients with medically intractable temporal lobe
      seizures was studied with long-term subdural videoelectroencephalographic
      monitoring. Temporal lobe seizure interhemispheric propagation time (IHPT) was
      found to be a negative, exponential function of electrocorticographic to clinical
      seizure onset time (ECOT) (f(x)=8.201x10(-0.016x), r=0.347, d.f.=35, t=2.19,
      p<0.05, where f(x)=IHPT and x=ECOT). A small increase in ECOT was associated with
      a substantial decrease in IHPT and vice versa. The results suggest the
      electrophysiological time factor, ECOT, involved in the transition from ictal EEG
      seizure onset to clinical seizure onset, may determine the speed of
      interhemispheric propagation of established epileptic activity. The results
      suggest the interesting hypothesis that, in human temporal lobe epilepsy and,
      perhaps, under non-pathological circumstances, the human temporal lobe might
      possess a "time-labeling" function amenable to quantitative analysis.

PMID- 16963241
TI  - Extraction and use of linguistic patterns for modelling medical guidelines.
AB  - OBJECTIVE: The quality of knowledge updates in evidence-based medical guidelines
      can be improved and the effort spent for updating can be reduced if the knowledge
      underlying the guideline text is explicitly modelled using the so-called
      linguistic guideline patterns, mappings between a text fragment and a formal
      representation of its corresponding medical knowledge. METHODS AND MATERIAL:
      Ontology-driven extraction of linguistic patterns is a method to automatically
      reconstruct the control knowledge captured in guidelines, which facilitates a
      more effective modelling and authoring of medical guidelines. We illustrate by
      examples the use of this method for generating and instantiating linguistic
      patterns in the text of a guideline for treatment of breast cancer, and evaluate
      the usefulness of these patterns in the modelling of this guideline. RESULTS: We
      developed a methodology for extracting and using linguistic patterns in guideline
      formalization, to aid the human modellers in guideline formalization and reduce
      the human modelling effort. Using automatic transformation rules for simple
      linguistic patterns, a good recall (between 72% and 80%) is obtained in selecting
      the procedural knowledge relevant for the guideline model, even though the
      precision of the guideline model generated automatically covers only between 20%
      and 35% of the human-generated guideline model. These results indicate the
      suitability of our method as a pre-processing step in medical guideline
      formalization. CONCLUSIONS: Modelling and authoring of medical texts can benefit
      from our proposed method. As pre-requisites for generating automatically a
      skeleton of the guideline model from the procedural part of the guideline text,
      to aid the human modeller, the medical terminology used by the guideline must
      have a good overlap with existing medical thesauri and its procedural knowledge
      must obey linguistic regularities that can be mapped into the control constructs
      of the target guideline modelling language.

PMID- 16963242
TI  - Application of sucrose fatty acid esters in transdermal therapeutic systems.
AB  - Transdermal therapeutic systems (TTSs) were studied applying different sucrose
      fatty acid esters (SEs) as drug delivery agents. Matrix and membrane controlled
      TTSs were prepared and compared. Membrane was made from a methacrylic polymer
      (Eudragit NE) of pH independent permeability which can achieve diffusion
      controlled drug liberation. Model drug was a water soluble beta-blocker,
      metoprolol, which has short biological half-life, so applying it in a TTS, the
      duration of its action could be prolonged. Sucrose fatty acid esters of different
      fatty acid chain lengths and consequently different hydrophilic-lipophilic
      balance (HLB) values were studied considering their effect on the metoprolol
      release from TTSs. Different mathematical models were applied for the evaluation
      of the release process. The results of the in vitro studies indicated that SEs of
      shorter fatty acid chain length and higher HLB value increased the amount of
      released drug about 10 times. SEs could be promising agents in transdermal
      therapeutic systems to control the drug release and cutaneous absorption.

PMID- 16963243
TI  - Mechanisms involved in the gastro-protective effect of STW 5 (Iberogast) and its
      components against ulcers and rebound acidity.
AB  - The protective effect of a commercial preparation (STW 5, Iberogast), containing
      the extracts of bitter candy tuft, lemon balm leaf, chamomile flower, caraway
      fruit, peppermint leaf, liquorice root, Angelica root, milk thistle fruit and
      greater celandine herb, against the development of gastric ulcers was previously
      reported in an earlier publication (Khayyal et al., 2001). All extracts produced
      a dose dependent anti-ulcerogenic effect associated with a reduced acid output,
      an increased mucin secretion, an increase in prostaglandin E(2) release and a
      decrease in leukotrienes. The effect on pepsin content was not uniform and did
      not seem to bear a relationship with the anti-ulcerogenic activity. The best
      effects were observed with the combined formulation, STW 5. Furthermore, the
      effect of the latter in protecting against the development of rebound gastric
      acidity was examined experimentally in rats and compared with the effect of some
      commercial antacid preparations (Rennie, Talcid and Maaloxan). A model of testing
      rebound acidity was developed by inducing a marginal increase in gastric acidity
      through the administration of indomethacin, in such a way that it could be easily
      neutralized, allowing any eventual secondary increase in acidity to be measured
      within a few hours of administration. In addition, the serum gastrin level was
      measured after drug treatment to establish any correlation between it and any
      rebound acidity. The results obtained demonstrated that STW 5 did not only lower
      the gastric acidity as effectively as the commercial antacid, but it was more
      effective in inhibiting the secondary hyperacidity. Moreover, STW 5 was capable
      of inhibiting the serum gastrin level in rats, an effect which ran parallel to
      its lowering effect on gastric acid production.

PMID- 16963244
TI  - Omega-3 fatty acids and monoamine neurotransmission.
AB  - We proposed several years ago that the behavioral effects of n-3 PUFA deficiency
      observed in animal models might be mediated through the dopaminergic and
      serotonergic systems that are very involved in the modulation of attention,
      motivation and emotion. We evaluated this hypothesis in an extended series of
      experiments on rats chronically diet-deficient in alpha-linolenic acid, the
      precursor of long-chain n-3 PUFA, in which we studied several parameters of these
      neurotransmission systems. The present paper synthesizes the main data we
      obtained on interactions between n-3 PUFA status and neurotransmission in animal
      models. We demonstrated that several parameters of neurotransmission were
      affected, such as the vesicular pool of dopamine and serotonin, thus inducing
      several regulatory processes such as modification of cerebral receptors in
      specific brain areas. We also demonstrated that (i) a reversal diet with adequate
      n-6 and n-3 PUFA given during the lactating period to rats originating from alpha
      linolenic acid-deficient dams was able to restore both the fatty acid composition
      of brain membranes and several parameters of the dopaminergic and serotonergic
      neurotransmission, and (ii) when given from weaning, this reversal diet allowed
      partial recovery of biochemical parameters, but no recovery of neurochemical
      factors. The occurrence of profound n-3 PUFA deficiency during the lactating
      period could therefore be an environmental insult leading to irreversible damage
      to specific brain functions. Strong evidence is now showing that a profound n-3
      PUFA experimental deficiency is able to alter several neurotransmission systems,
      at least the dopaminergic and serotonergic. Whether these experimental findings
      can be transposed to human pathophysiology must be taken cautiously, but
      reinforces the hypothesis that strong links exist between the PUFA status,
      aspects of brain function such as neurotransmission processes and behavior.

PMID- 16963245
TI  - Risk factors for pulmonary complications after emergency abdominal surgery.
AB  - OBJECTIVE: Pulmonary complications are common after abdominal surgery. Although a
      variety of risk factors have been described for these complications, studies so
      far have focused on elective interventions. The aim of this study was to
      determine the incidence and predictors of pulmonary complications following
      emergency abdominal surgery. METHODS: This was a prospective cohort study. Pre
      and intra-operative data were collected through interview and chart review and
      their association with the occurrence of postoperative pulmonary complications
      (PPC) were analyzed. RESULTS: Two hundred and sixty-six consecutive adult
      patients were included and seventy-five (28.2%) developed PPC. Age >50 years
      (adjusted OR=3.86; P<0.001), body mass index (BMI) <21 kg/m(2) or 30 kg/m(2)
      (adjusted OR=2.43; P=0.007) and upper or upper/lower abdominal incision (adjusted
      OR=2.57; P=0.027) were independently associated with PPC. Patients submitted to
      multiple procedures tended to be at a higher risk for PPC (adjusted OR=1.73;
      P=0.079). The development of PPC was associated with prolonged hospital stay
      (P<0.001) and increased death rate (P<0.001). CONCLUSIONS: Pulmonary
      complications are frequent among patients undergoing abdominal emergency surgery
      and lead to increased length of hospital stay and death rate. Older age, abnormal
      BMI, upper or upper/lower abdominal incision and multiple procedures are
      predictors of PPC in this setting.

PMID- 16963246
TI  - Genetic and nutritional deficiencies in folate metabolism influence
      tumorigenicity in Apcmin/+ mice.
AB  - Epidemiological studies indicate that adequate dietary folate is protective
      against colon cancer, although mechanisms remain largely elusive. We investigated
      the effects of genetic disruptions of folate transport and metabolism and of
      dietary folate deficiency in a mouse model of colon cancer, the Apc(min/+) mouse.
      Apc(min/+) mice with heterozygous knockout of the gene for reduced folate carrier
      1 (Rfc1(+/-)) developed significantly fewer adenomas compared to
      Rfc1(+/+)Apc(min/+) mice [30.3+/-4.6 vs. 60.4+/-9.4 on a control diet (CD) and
      42.6+/-4.4 vs. 55.8+/-7.6 on a folate-deficient diet, respectively]. Rfc1(+/
      )Apc(min/+) mice also carried a lower tumor load, an indicator of tumor size as
      well as of tumor number. In contrast, there were no differences in adenoma
      formation between Apc(min/+) mice carrying a knockout allele for methionine
      synthase (Mtr(+/-)), an enzyme that catalyzes folate-dependent homocysteine
      remethylation, and Mtr(+/+)Apc(min/+) mice. However, in both Mtr groups of mice,
      dietary folate deficiency significantly increased adenoma number (from 32.3+/-3.8
      on a CD to 48.1+/-4.2 on a folate-deficient diet), increased plasma homocysteine,
      decreased global DNA methylation in preneoplastic intestines and increased
      apoptosis in tissues. There were no genotype-associated differences in these
      parameters in the Rfc1 group, suggesting that the protection conferred by Rfc1
      deficiency is carried out through a different mechanism. In conclusion, genetic
      and nutritional disturbances in folate metabolism can have distinct influences on
      tumorigenesis in Apc(min/+) mice; altered levels of homocysteine, global DNA
      methylation and apoptosis may contribute mechanistically to dietary influence.

PMID- 16963247
TI  - Protective mechanisms of the Mediterranean diet in obesity and type 2 diabetes.
AB  - The prevalence of obesity has grown to an alarming level of at least 300 million
      people worldwide. Additionally, a diabetes epidemic is underway, with an estimate
      of 217 million people with diabetes worldwide. There are many links between
      excessive body weight and type 2 diabetes, and one common and fundamental cause
      of both epidemics is an unhealthy diet. Research to identify and promote diets
      that protect individuals from obesity and type 2 diabetes is urgently needed. The
      Mediterranean diet, a concept developed in the 1950s, refers to dietary habits of
      individuals from the Mediterranean basin. The Mediterranean diet is an eating
      pattern that successfully combines pleasant taste and positive health effects.
      The Mediterranean diet does not stand for a homogenous and exclusive model among
      the Mediterranean basin population but rather represents a set of healthy dietary
      habits, including high consumption of vegetables and fresh fruits and the use of
      olive oil as the main source of fat. Evidence from epidemiological studies
      supports a protective effect of this dietary pattern on weight gain and the
      development of type 2 diabetes. Several mechanistic explanations link
      characteristic components of the Mediterranean diet with obesity and type 2
      diabetes. This review will discuss potential mechanisms by which the
      Mediterranean diet protects individuals from both diseases.

PMID- 16963249
TI  - Docosahexaenoic acid induces apoptosis in CYP2E1-containing HepG2 cells by
      activating the c-Jun N-terminal protein kinase related mitochondrial damage.
AB  - Docosahexaenoic acid (DHA) causes apoptosis of various cancer cells, but the
      mechanism of DHA-induced cell death is still unclear. We hypothesized that the
      early signaling of apoptosis may be important in causing cell death as well as
      the production of free radical metabolites. DHA caused time- and dose-dependent
      cell death in human HepG2 hepatoma cells transduced with CYP2E1 (E47) but not in
      C34 (without CYP2E1), suggesting an important role of CYP2E1 in the DHA-mediated
      damage. DHA increased the c-Jun N-terminal protein kinase (JNK) activity until 8
      h without activating other mitogen-activated protein kinases. The contents of
      proapoptotic Bad and FasL at 4 h and cytochrome c and caspase 3 activity at 8 h
      were increased and accompanied by the JNK activation in a successive manner. In
      contrast, Bax and Bcl-2 were not changed. Levels of lipid peroxides (LPOs) were
      elevated three- and fivefold at 8 and 24 h, respectively, in DHA-induced E47
      cells. However, pretreatment with chlormethiazole (CMZ), a specific inhibitor of
      CYP2E1, significantly reduced the levels of LPO, CYP2E1, JNK activity and the
      rate of cell death. In addition, pretreatment with quercetin (one as a JNK
      inhibitor and one as an antioxidant) significantly reduced the cell death rate
      and JNK and SEK-1 activities. Our results indicated that DHA-mediated apoptosis
      in E47 cells was induced through the activation of the JNK-related cell death
      pathway, which may be involved in the production of LPO or reactive oxygen
      species during the CYP2E1 catalytic cycle, followed by mitochondrial injury and
      apoptosis.

PMID- 16963248
TI  - Dietary isoflavones differentially induce gene expression changes in lymphocytes
      from postmenopausal women who form equol as compared with those who do not.
AB  - Human and animal studies suggest that dietary soy isoflavones reduce cancer risk,
      ameliorate postmenopausal syndrome and decrease bone resorption in postmenopausal
      women. The capacity to form the metabolite equol from daidzein is suggested as an
      important modulator of response to isoflavones; this capacity depends on gut
      colonization with appropriate bacteria. We administered a dietary supplement
      containing high-dose purified soy isoflavones (genistein, 558 mg/day; daidzein,
      296 mg/day; and glycitein, 44 mg/day) to 30 postmenopausal women for 84 days and
      collected peripheral lymphocytes at timed intervals. Using microarray analysis,
      we determined whether changes in gene expression associated with this treatment
      support existing hypotheses as to isoflavones' mechanisms of action. Expression
      of a large number of genes was altered by isoflavone treatment, including
      induction of genes associated with cyclic adenosine 3',5'-monophosphate (cAMP)
      signaling and cell differentiation and decreased expression of genes associated
      with cyclin-dependent kinase activity and cell division. We report that
      isoflavone treatment in subjects who have the capacity to produce equol
      differentially affects gene expression as compared with nonproducers, supporting
      the plausibility of the importance of equol production. In general, isoflavones
      had a stronger effect on some putative estrogen-responsive genes in equol
      producers than in nonproducers. Our study suggests that, in humans, isoflavone
      changes are related to increased cell differentiation, increased cAMP signaling
      and G-protein-coupled protein metabolism and increased steroid hormone receptor
      activity and have some estrogen agonist effects; equol-production status is
      likely to be an important modulator of responses to isoflavones.

PMID- 16963250
TI  - Effect of fish oil on bone mineral density in aging C57BL/6 female mice.
AB  - Life expectancy has increased considerably over the last century in the United
      States. It is expected that this longevity will be accompanied by an increase in
      the prevalence of osteoporosis and accompanying complications in the elderly
      population. Age-related loss of bone mass and bone fragility are major risk
      factors for osteoporosis, leading to an increased risk of fractures. Therefore,
      nutritional strategies and lifestyle changes that prevent age-related
      osteoporosis and improve the quality of life for the elderly population are
      urgently needed. Hence, the present study compared the effects of corn oil (CO; n
      6 fatty acids; commonly present in Western diets) and fish oil (FO; n-3 fatty
      acids) on bone mineral density (BMD) in aging C57BL/6 female mice. After 6 months
      of dietary treatment, we found that 18-month-old FO-fed mice maintained higher
      BMD in different bone regions compared to CO-fed mice. These findings were
      accompanied by a decreased activity of pro-inflammatory cytokines, tumor necrosis
      factor-alpha and interleukin-6 in stimulated splenocytes; a nonsignificant but
      greater increase in bone formation markers alkaline phosphatase and osteocalcin
      in the serum; and lower osteoclast generation in bone marrow cell cultures in FO
      fed mice. In conclusion, these findings suggest that providing n-3 fatty acids
      may have a beneficial effect on bone mass during aging by modulating bone
      formation and bone resorption factors.

PMID- 16963251
TI  - Epigallocatechin-3-gallate increases the formation of mineralized bone nodules by
      human osteoblast-like cells.
AB  - Consumption of green tea, a rich source of epigallocatechin-3-gallate (EGCG), is
      associated with increased bone mineral density. However, the direct effects of
      this flavonoid on bone mineralization are not known. The present study
      demonstrates the effects of EGCG on the formation of mineralized bone nodules by
      SaOS-2 human osteoblast (HOB)-like cells. EGCG at concentrations of 1-5 microM
      caused a dose-dependent increase in the number and area of mineralized bone
      nodules as assessed by both von Kossa and alizarin red staining. EGCG also
      increased alkaline phosphatase activity, an early marker of osteoblastic
      differentiation. After 48 h of treatment, EGCG decreased protein levels of Runx2,
      a transcription factor that regulates osteoblast maturation by inhibiting late
      stage differentiation. The observed effects of EGCG on bone formation by HOB-like
      cells suggest that EGCG may have beneficial effects on bone health.

PMID- 16963252
TI  - Conjugated linoleic acid inhibits Caco-2 cell growth via ERK-MAPK signaling
      pathway.
AB  - Conjugated linoleic acid (CLA) is a naturally occurring compound found in dairy
      and beef products. In recent years, it has received considerable attention
      because several studies showed a lower incidence of certain cancers in animals
      fed CLA-supplemented diets. In vitro studies further showed growth inhibitory
      activity on tumor cell proliferation, the CLA being effective above all against
      colon cancer cells. The aim of the present work was to investigate the growth
      inhibitory effect of CLA on Caco-2 cell line. Under our experimental conditions,
      CLA repressed Caco-2 cell proliferation, and the growth-inhibitory action
      increased by repeating treatments. However, in Caco-2 cells, CLA was unable to
      induce apoptosis, as revealed by cell-cycle analysis and Western blot studies. To
      determine the mechanism by which CLA inhibits cell growth, we studied its effect
      on extracellular-regulated kinase signaling. Conjugated linoleic acid reduced
      expression levels of Raf-1 and phosphorylation of ERK1/2, which was accompanied
      by a decrease in the expression of the downstream transcription factor c-myc. Our
      data suggest that CLA is dependent, at least in part, on the ERK kinase pathway
      for its ability to inhibit the growth of Caco-2 cancer cells.

PMID- 16963253
TI  - Regulation of adipocyte differentiation by PEGylated all-trans retinoic acid:
      reduced cytotoxicity and attenuated lipid accumulation.
AB  - Obesity is major risk factor for many disorders, including diabetes, hypertension
      and heart disease. Unfortunately, there is a dearth of therapeutic agents
      available to clinicians for the treatment of obesity. The principal aim of this
      study was to investigate whether PEGylated all-trans retinoic acid (PRA) can have
      favorable stability and biological activity in 3T3-L1 preadipocytes as an
      antiobesity drug. Here, we found that PRA inhibits the process of adipogenesis,
      including survival of adipocytes and differentiation to mature adipocytes. The
      results showed that RA nanoparticles (NPs) were prepared by PEGylation; below 200
      nm, PRA-NPs were obtained. Moreover, PRA decreased glycerol-3-phosphate
      dehydrogenase activity in 3T3-L1 preadipocytes by acting with major adipocyte
      marker proteins such as PPARgamma2, C/EBPalpha and aP2 modulators. Apoptosis, in
      addition, increased as the level of RA increased from 10 to 20 microM, whereas
      PRA reduced apoptosis with increasing concentrations. Our data suggest that PRA
      NP has potential as an antiobesity drug carrier due to its small particle size
      and PEGylated core-shell structure. In addition, our results suggest that PRA
      inhibits the process of adipogenesis and may be developed to treat obesity. Based
      on these results, PRA is suitable for adipocyte studies, and an enhanced effect
      of PRA with adipocyte differentiation offers a challenging approach for
      pharmaceutical applications.

PMID- 16963254
TI  - Road soil retention of Pb leached from MSWI bottom ash.
AB  - Municipal solid waste incinerator (MSWI) bottom ash may be used as a road
      construction material; it potentially contains however a sizable quantity of
      heavy metals, which under the effect of rainfall infiltration through the road
      structure can be leached out from the material and infiltrate into the underlying
      soil. An eco-compatibility assessment of MSWI bottom ash reuse in road
      construction applications necessitates examining the solubility and retention of
      heavy metals in road soils. This study is dedicated to Pb transfer, sorption and
      desorption (NEN 7341 standard test) within various soils. These experiments yield
      results relative to the interaction between road soils and an MSWI bottom ash
      leachate representative of a "fresh" product, with a high leaching potential. For
      the soils investigated, the sorption of lead varies between 90% and 99%. For an
      extraction at pH 7, Pb release is very low (<2%) for all soils, while at pH 4
      leaching varies between 4% and 47%. This work shows that Pb may be fixed by some
      types of road soil in mostly stable forms.

PMID- 16963255
TI  - Electrochemical biosensing utilizing synergic action of carbon nanotubes and
      platinum nanowires prepared by template synthesis.
AB  - Platinum nanowires (PtNWs) prepared by electrodeposition method with the help of
      porous anodic aluminum oxide (AAO) templates have been solubilized in chitosan
      (CHIT) together with carbon nantubes (CNTs) to form a PtNW-CNT-CHIT organic
      inorganic system. The resulting PtNW-CNT-CHIT material brings capabilities for
      utilizing synergic action of PtNWs and CNTs to facilitate electron-transfer
      process in electrochemical sensor design. The PtNW-CNT-CHIT film modified
      electrode offered a significant decrease in the overvoltage for the hydrogen
      peroxide and showed to be excellent amperometric sensors for hydrogen peroxide at
      -0.1 V over a wide range of concentrations, and the sensitivity is 260 microAmM
      1cm-2. As an application example, by linking glucose oxidase (GOx), an amplified
      biosensor toward glucose was prepared. The glucose biosensor exhibits a selective
      determination of glucose at -0.1 V with a linear response range of 5 x 10(-6) to
      1.5 x 10(-2)M with a correlation coefficient of 0.997, and response time <10s.
      The high sensitivity of the glucose biosensor is up to 30 microAmM-1cm-2 and the
      detection limit was 3 microM. The biosensor displays rapid response and expanded
      linear response range, and excellent repeatability and stability.

PMID- 16963256
TI  - QCM detection of DNA targets with single-base mutation based on DNA ligase
      reaction and biocatalyzed deposition amplification.
AB  - A novel biosensing technique for highly specific identification of gene with
      single-base mutation is proposed based on the implementation of the DNA ligase
      reaction and the biocatalyzed deposition of an insoluble product. The target gene
      mediated deposition of an insoluble precipitate is then transduced by quartz
      crystal microbalance (QCM) measurements. In this method, the DNA target
      hybridizes with a capture DNA probe tethered onto the gold electrode and then
      with a biotinylated allele-specific detection DNA. A ligase reaction is performed
      to generate the ligation between the capture and the detection probes, provided
      there is perfect match between the DNA target and the detection probe. Otherwise
      even when there is an allele mismatch between them, no ligation would take place.
      After thermal treatment at an elevated temperature, the formed duplex melts apart
      that merely allows the detection probe perfectly matched with the target to
      remain on the electrode surface. The presence of the biotinylated allele-matched
      probe is then detected by the QCM via the binding to streptavidin-peroxide
      horseradish (SA-HRP), which catalyzes the oxidative precipitation of 3,3
      diaminobenzidine (DAB) by H2O2 on the electrode and provides an amplified
      frequency response. The proposed approach has been successfully implemented for
      the identification of single-base mutation in -28 site of the beta-thalassemia
      gene with a detection limit of 0.1 nM, demonstrating that this method provides a
      highly specific and cost-efficient approach for point mutation detection.

PMID- 16963258
TI  - Neutron protein crystallography: current status and a brighter future.
AB  - Hydrogen atoms are rarely seen in X-ray protein crystal structures, but are
      readily visualized by neutron crystallography, even at typical (1.5-2.5A)
      resolutions. Recent advances in neutron beamlines and deuterium labeling
      technologies have dramatically extended the scale and range of structures
      studied. High-quality neutron data can be collected to near atomic resolution (
      approximately 1.5-2.5A) for proteins of 50-175kDa molecular weight, from
      perdeuterated samples, from crystals with volumes of 0.1mm(3) and at cryogenic
      temperatures (15K). These structures are providing unique and complementary
      insights into hydrogen-bonding interactions, protonation states, catalytic
      mechanisms and hydration states of biological structures that are not available
      from X-ray analysis alone. The new generation of spallation neutron sources
      promises further 10-50-fold gains in performance.

PMID- 16963259
TI  - Analytical strategies to investigate plant N-glycan profiles in the context of
      plant-made pharmaceuticals.
AB  - Plants are attractive hosts for the production of recombinant proteins. However,
      their inability to process authentic human N-glycan structures imposes a major
      limitation on their use as expression systems for therapeutic products. Several
      strategies have emerged to engineer plant N-glycans into human-compatible
      molecules. In this context, fast and reliable analytical strategies for the
      identification of plant N-glycan profiles have been developed to define the N
      glycosylation pathways of crops, to monitor the production of plant-made
      pharmaceuticals and to assess in planta remodelling strategies.

PMID- 16963260
TI  - What clinicians need to know about antioestrogen resistance in breast cancer
      therapy.
AB  - Tamoxifen is the drug most used for early breast cancer treatment in oestrogen
      receptor (ER) positive patients. Unfortunately, despite high ER tumour levels in
      a tumour, resistance to endocrine therapy, either de novo or acquired after
      prolonged treatment, can occur. In this review, we will try to summarise the
      postulated mechanisms of hormonal-resistance, namely, the role of co-regulators
      and the crosstalk between the HER-2, IGF-IR, Cox-2 and ER pathways. Other
      predictive markers of tamoxifen-resistance/response, such as cyclin E and UPA/PAI
      1, are also discussed.

PMID- 16963261
TI  - Changes in bone and lipid metabolism in postmenopausal women with early breast
      cancer after terminating 2-year treatment with exemestane: a randomised, placebo
      controlled study.
AB  - Aromatase inhibitors improve relapse-free survival in early breast cancer, but
      there is concern about possible detrimental effects on bone mineral density (BMD)
      and plasma lipids. This paper presents the results of a 2-year study evaluating
      the effects of exemestane versus placebo on BMD, bone markers, plasma lipids and
      coagulation factors, including a 1-year follow-up after termination of treatment
      in 147 patients. During treatment, the mean annual rate of loss of BMD in the
      lumbar spine was 2.17% in the exemestane group versus 1.84% in the placebo group
      (n.s.) and 2.72% versus 1.48%, respectively, in the femoral neck (P=0.024). A
      loss of BMD above that expected in both arms of this study could be due to low
      vitamin D status (88% of all patients had vitamin D levels <30 ng/ml). The
      changes observed with exemestane were partially reversed during a 1-year follow
      up, with no significant difference between the two arms. Similarly, the moderate
      decrease in high-density lipoprotein (HDL)-cholesterol was reversed. The bone
      marker values decreased, although a difference at 6 months of follow-up was still
      recorded, in particular for the markers of bone synthesis.

PMID- 16963262
TI  - Identification of germline MLH1 alterations in familial prostate cancer.
AB  - Several linkage and loss of heterozygosity (LOH) analyses suggest that the region
      3p21-p26, which is a chromosomal location of MLH1, could harbour a susceptibility
      gene for prostate cancer (PRCA). Furthermore, in a recent candidate single
      nucleotide polymorphism (SNP) analysis the I219V variation of the MLH1 gene was
      associated with PRCA. Microsatellite instability (MSI) and germ-line MLH1
      mutations were originally demonstrated in hereditary non-polyposis colorectal
      cancer (HNPCC) but MSI and loss of MLH1 function have also been detected in PRCA.
      To assess the contribution of MLH1 germline mutations to the development of PRCA
      in Finland different approaches were used. First, the samples from 11 PRCA-colon
      cancer patients were screened for MLH1, MSH2 and MSH6 protein expression by
      immunohistochemistry (IHC). IHC revealed one patient with a putative MLH1
      aberration and sequencing of this sample revealed five sequence variants
      including two missense variants P434L and I219V. Second, the samples from Finnish
      hereditary prostate cancer (HPC) families were used for the screening of MLH1
      mutations which produced twelve MLH1 sequence variants including two missense
      mutations, I219V, as in the PRCA-colon cancer patient, and V647M. P434L and V647
      were both novel, rare variants. Carrier frequencies of the I219V mutation were
      compared between hereditary prostate cancer (HPC) patients, unselected PRCA
      cases, patients with benign prostate hyperplasia and controls, but no differences
      between the sample groups were found. P434L was not present in this study
      population and V647M was a very rare variant found only in one HPC family.
      According to the present results, MLH1 does not have a major role in PRCA
      causation in Finland.

PMID- 16963263
TI  - JAK/STAT signalling pathway in colorectal cancer: a new biological target with
      therapeutic implications.

PMID- 16963264
TI  - Discovery of potent, efficacious, and orally bioavailable inhibitors of blood
      coagulation factor Xa with neutral P1 moieties.
AB  - The bicyclic dihydropyrazolopyridinone scaffold allowed for incorporation of
      multiple P1 moieties with subnanomolar binding affinities for blood coagulation
      factor Xa. The compound 3-[6-(2'-dimethylaminomethyl-biphenyl-4-yl)-7-oxo-3
      trifluoro-methyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridine-l-yl]-benzamide 6d
      shows good fXa potency, selectivity, in vivo efficacy and oral bioavailability.
      Compound 6d was selected for further pre-clinical evaluations.

PMID- 16963265
TI  - The automatic production of 16alpha-[18F]fluoroestradiol using a conventional
      [18F]FDG module with a disposable cassette system.
AB  - We have developed a fully automatic method for the synthesis of 16alpha
      [18F]fluoroestradiol ([18F]FES) using a disposable cassette system and
      conventional [18F]FDG module. [18F]FES was synthesized using a GE TracerLab MX
      module and a modified module control program. Following [18F]fluorination, we
      hydrolyzed the product three times with a mixture of 2N HCl and CH(3)CN. After
      HPLC purification, the decay corrected radiochemical yield of [18F]FES was 45.3+/
      2.8%, which was stable to 98.2+/-0.2% at 6h after synthesis. This new automated
      synthesis method provides high and reproducible yields with the advantage of a
      disposable cassette system.

PMID- 16963266
TI  - Natural and anthropogenic radionuclides in rocks and beach sands from Ezine
      region (Canakkale), Western Anatolia, Turkey.
AB  - This paper represents the first reports on the natural and anthropogenic
      radionuclides in Kestanbol granitic pluton and surrounding rocks, and coastal
      region of the Ezine town. To assess the radiological hazard of the natural
      radioactivity, the radium equivalent activity, the absorbed dose rate and the
      external hazard index were calculated, and in situ gamma dose rates were
      measured. The high-activity concentrations were measured in the pluton and sands,
      which was originated mainly from the pluton, due to the presence of zircon,
      allanite, monazite, thorite, uranothorite and apatite. The average activity
      concentrations of (238)U, (232)Th and (40)K are 174.78, 204.69 and 1171.95 Bq kg(
      1) for pluton, and 290.36, 532.04 and 1160.75 Bq kg(-1) for sands, respectively.
      (137)Cs in Ezine region ranged from 0-6.57 Bq kg(-1). The average absorbed dose
      rate for the granitic and sand samples were calculated to be 251.6 and 527.92 nGy
      h(-1), respectively. The maximum contribution to the total absorbed gamma dose
      rate in air was due to the (232)Th (52.3% for pluton and 67.1% for sands). The
      Raeq activities of the pluton and sands are higher than the recommended maximum
      value of 370 Bq kg(-1) criterion limit of Raeq activity for building materials.

PMID- 16963268
TI  - Repair of skin covering osteoradionecrosis of the mandible with the
      fasciocutaneous supraclavicular artery island flap: case report.
AB  - INTRODUCTION: Osteoradionecrosis of the mandible is a serious complication
      following radiotherapy for head and neck cancer. Reconstructive procedures in the
      head and neck region use a wide range of flaps for defect closure. The methods
      range from local, mostly myocutaneous flaps and skin grafts to free microsurgical
      flaps to ensure a satisfactory functional and aesthetic result. Moreover, the
      donor site defect needs to be closed, with as little as possible functional or
      aesthetic impairment. PATIENT AND METHOD: A 60-year-old male is presented with a
      history of squamous cell carcinoma of the left lower lip and chin area in whom
      the tumour was resected and treated by adjuvant radiotherapy. The follow-up was
      complicated by chronic inflammation of the left mandibular body as a sequel of
      radiotherapy; it resulted with partial bone destruction, and soft tissue
      dehiscence. He was admitted for repair and treatment of the infected mandibular
      osteoradionecrosis. A supraclavicular artery island flap was used to close the
      mandibular soft tissue defect. CONCLUSION: The shoulder provides a relatively
      good skin texture and match to provide cover and lining for defects in the lower
      part of the face, in combination with minor donor site morbidity.

PMID- 16963267
TI  - Transgenic mice overexpressing the full-length neurotrophin receptor TrkC exhibit
      increased catecholaminergic neuron density in specific brain areas and increased
      anxiety-like behavior and panic reaction.
AB  - Accumulating evidence has suggested that neurotrophins participate in the
      pathophysiology of mood disorders. We have developed transgenic mice
      overexpressing the full-length neurotrophin-3 receptor TrkC (TgNTRK3) in the
      central nervous system. TgNTRK3 mice show increased anxiety-like behavior and
      enhancement of panic reaction in the mouse defense test battery, along with an
      increase in the number and density of catecholaminergic (tyrosine hydroxylase
      positive) neurons in locus coeruleus and substantia nigra. Furthermore, treatment
      of TgNTRK3 mice with diazepam significantly attenuated the anxiety-like behaviors
      in the plus maze. These results provide evidence for the involvement of TrkC in
      the development of noradrenergic neurons in the central nervous system with
      consequences on anxiety-like behavior and panic reaction. Thus, changes in TrkC
      expression levels could contribute to the phenotypic expression of panic disorder
      through a trophic effect on noradrenergic neurons in the locus coeruleus. Our
      results demonstrate that the elevated NT3-TrkC tone via overexpression of TrkC in
      the brain may constitute a molecular mechanism for the expression of anxiety and
      anxiety.

PMID- 16963269
TI  - Asterion as a surgical landmark for lateral cranial base approaches.
AB  - INTRODUCTION: When approaching the posterior fossa and posterolateral cranial
      base, surface landmarks are helpful in locating the junction of the transverse
      and the sigmoid sinus. MATERIAL AND METHODS: On 100 skull halves a 2mm drill bit
      was externally placed over the asterion and was drilled through the bone
      perpendicular to the skull surface. Various positions of the asterion and its
      distance from the root of the zygomatic process of the temporal bone, from the
      suprameatal crest and the mastoid tip were investigated. RESULTS: The position of
      the asterion has been found to be located superficial to the transverse-sigmoid
      sinus junction in 87% of all samples, inferior to the transverse-sigmoid sinus
      junction in 11% and superior to the transverse-sigmoid sinus junction in 2%. The
      distance from the asterion to the root of the zygoma has been determined to be
      54.6+/-5.5mm. The distance between asterion and Henle's spine was 45.2+/-5.2, and
      from asterion to Frankfurt Horizontal Plane 15+/-7.5mm. CONCLUSION: Asterion
      varies regarding its cephalocaudal position. The findings of this study might
      have direct consequences for transmastoid and retrosigmoid approaches for
      microvascular trigeminal root decompression and combined petrosal approaches.

PMID- 16963270
TI  - Reasons for miniplate removal following maxillofacial trauma: a 4-year study.
AB  - INTRODUCTION: There is still no consensus on the need for routine removal of
      titanium miniplates in the maxillofacial skeleton. The purpose of this 4-year
      prospective study was to evaluate the reasons for removal of titanium miniplates
      ("2.0mm") following maxillofacial trauma. MATERIAL AND METHODS: Records of 280
      patients were evaluated concerning the number of plates inserted, the site of
      plating, the number of patients in whom plates were removed, the site of removal
      and the reasons for which removal of plates was indicated. RESULTS: In the 280
      patients with facial trauma, 599 miniplates were used during this period. Thirty
      seven miniplates were removed from 27 of these patients. The main causes for
      removal were infection and exposure of the plate in the oral cavity, patients'
      request and/or the plates being palpable. The nasofrontal region, the area around
      the anterior wall of the antrum and the body of the mandible proved to be the
      commonest regions where plate removal was required. CONCLUSION: The number of
      miniplates removed was small but not insignificant. There is no evidence from
      this study to support advice for the routine removal of titanium miniplates from
      the maxillofacial skeleton.

PMID- 16963271
TI  - Cellular therapy and myocardial tissue engineering: the role of adult stem and
      progenitor cells.
AB  - Acquired cardiovascular diseases and complex congenital heart diseases are
      leading causes of morbidity and mortality. Cellular therapy and tissue
      engineering are emerging as promising alternative approaches to treat
      cardiovascular diseases. Cellular therapy involves isolating cells and delivering
      the cells to the site of cardiac injury to restore blood flow and contractility
      to previously infarcted, scarred or dysfunctional heart. Myocardial tissue
      engineering, engineered heart tissue by seeding cells in three-dimensional
      matrices of biodegradable polymers or cell sheet engineering without artificial
      scaffolds to form new myocardial constructs. Questions are common to both these
      approaches, such as the best cell source and optimal conditions for therapeutic
      application. The capabilities of stem cells for pluripotency and long-term self
      renewal make it an ideal source for myocardial tissue engineering and cell
      therapy. We review the current understanding of postnatal adult stem and
      progenitor cells in cellular therapy and myocardial tissue engineering from a
      surgical view point, and highlight the latest advances in these exciting fields.

PMID- 16963272
TI  - The objective assessment of lifetime cumulative ultraviolet exposure for
      determining melanoma risk.
AB  - Exposure to ultraviolet radiation has commonly been recognized as the most
      important environmental risk factor for melanoma. The measurement of UV exposure
      in humans, however, has proved challenging. Despite the general appreciation that
      an objective metric for individual UV exposure is needed to properly assess
      melanoma risk, little attention has been given to the issue of accuracy of UV
      exposure measurement. The present research utilized a GIS based historical UV
      exposure model (for which the accuracy of exposure estimates is known) and
      examined, in the case-control setting, the relative importance of UV exposure
      compared to self-reported time spent outdoors, in melanoma risk. UV estimates
      were coupled with residential histories of 820 representative melanoma cases
      among non-Hispanic white residents under 65 years of age from Los Angeles County
      and for 877 controls matched to cases by age, sex, race, and neighborhood of
      residence, to calculate the cumulative lifetime UV exposure and average annual UV
      exposure. For historical measures, when the participants resided outside the US,
      we also calculated UV estimates. While there was no increased risk of melanoma
      associated with self-reported time spent outdoors, the association between annual
      average UV exposure based on residential history and melanoma risk was
      substantial, as was the association between cumulative UV exposure based on
      residential history and melanoma. The time spent in outdoor activities appeared
      to have no significant effect on melanoma risk in any age strata, however, when
      adjusted for UV exposure based on residential history, time spent outdoors during
      young age significantly increased risk for melanoma. While there was some
      attenuation of risk when we excluded data from people resident overseas (as all
      other studies we are aware of have done), this did not significantly impact
      subsequent risk estimates of UV exposure on melanoma.

PMID- 16963273
TI  - Potential of photodynamic therapy in treatment of fungal infections of the mouth.
      Design and characterisation of a mucoadhesive patch containing toluidine blue O.
AB  - Mucocutaneous oropharyngeal candidiasis is predominately caused by Candida
      albicans. The overall incidence of oral candidiasis in young adults has increased
      dramatically with the spread of HIV/AIDS. Conventional treatments have been shown
      to have a fungistatic rather than a fungicidal effect, resulting in an inadequate
      treatment outcome for patients. In addition, increasing resistance of C. albicans
      to antifungal agents has made effective treatment more difficult. Accordingly,
      interest has arisen in development of new prophylaxis/treatment regimens. One
      such alternative treatment is photodynamic antimicrobial chemotherapy (PACT), in
      which a combination of a photosensitising drug and visible light cause selective
      destruction of microbial cells. Due to the highly coloured nature of
      photosensitisers and the potential for staining of teeth, lips and buccal mucosa,
      administration of photosensitisers to humans as a liquid mouthwash is
      undesirable. Targeted delivery of the photosensitiser directly to the site of
      infection should be the aim. The current study, therefore, reports on a
      mucoadhesive patch containing toluidine blue O (TBO), as a potential delivery
      system for use in PACT of oropharyngeal candidiasis. Patches prepared from
      aqueous blends of poly(methyl vinyl ether/maleic anhydride) and
      tripropyleneglycol methyl ether possessed suitable properties for use as
      mucoadhesive drug delivery systems and were capable of resisting dissolution when
      immersed in artificial saliva. When releasing directly into an aqueous sink,
      patches containing 50 and 100mg TBO cm(-2) both generated receiver compartment
      concentrations exceeding the concentration (2.0-5.0 mg ml(-1)) required to
      produce high levels of kill (>90%) of both planktonic and biofilm-grown C.
      albicans upon illumination. However, the concentrations of TBO in the receiver
      compartments separated from patches by membranes intended to mimic biofilm
      structures were an order of magnitude below those inducing high levels of kill,
      even after 6h release. Therefore, short application times of TBO-containing
      mucoadhesive patches should allow treatment of recently-acquired oropharyngeal
      candidiasis, caused solely by planktonic cells. Longer patch application times
      may be required for persistent disease where biofilms are implicated.

PMID- 16963274
TI  - The effect of adenosine receptor agonists on cytokine release by human
      mononuclear cells depends on the specific Toll-like receptor subtype used for
      stimulation.
AB  - In the present study, we determined whether the immunomodulatory effect of
      adenosine receptor stimulation depends on the Toll-like Receptor (TLR) used for
      stimulation of cytokine release. Therefore, human mononuclear cells were
      stimulated by different TLR agonists in the absence and presence of A1 (CPA), A2a
      (CGS21680), and A3 (Cl-IB-MECA) adenosine receptor agonists. Effects of these
      agonists on Il-6, Il-10, IFN-gamma, TNF-alpha, and Il-1beta production were
      expressed as percentage inhibition/stimulation after TLR stimulation. CGS21680
      inhibited TLR4-mediated TNF-alpha release and potentiated TLR3- and TLR5-mediated
      IL-6 release. Cl-IB-MECA inhibited TLR4-agonist-induced IFN-gamma release.
      Interestingly, CPA en Cl-IB-MECA tended to inhibit cytokine release only after
      TLR4 stimulation. In more detail, CPA potentiated TLR5-mediated IL-6 production,
      TLR3-mediated IFN-gamma production and TLR3-mediated Il-1beta-production compared
      to TLR4-mediated stimulation. Cl-IB-MECA potentiated TLR5-mediated IL-6 and Il
      1beta formation as compared to TLR4-mediated stimulation. Finally, CGS21680
      potentiated TLR5-mediated IL-6 production compared to TLR1-2 stimulation, and
      potentiated TLR3- and TLR5-mediated IL-10 production compared to TLR1-2-mediated
      stimulation. In conclusion, the effect of adenosine agonists on cytokine
      production depends on the specific TLR agonist used for stimulation. These
      findings suggest that well-known anti-inflammatory effects of adenosine agonists
      on LPS-induced inflammation cannot be extrapolated to situations in which
      stimulation of other TLR subtypes is involved.

PMID- 16963276
TI  - Charge location directs electron capture dissociation of peptide dications.
AB  - The effect of peptide dication charge location on electron capture dissociation
      (ECD) fragmentation pattern is investigated. ECD fragmentation patterns are
      compared for peptides with amide and free acid C-terminal groups. ECD of free
      acid compared with C-terminally amidated peptides with basic residues near the N
      terminus demonstrates increased formation of a-type ions. Similarly, ECD of free
      acid compared with C-terminally amidated peptides with basic residues near the C
      terminus exhibits increased formation of y-type ions. Alteration of the peptide
      sequence to inhibit the formation of charged side chains (i.e., amino acid
      substitution and acetylation) provides further evidence for charge location
      effect on ECD. We propose that formation of zwitterionic peptide structures
      increases the likelihood of amide nitrogen protonation (versus basic side
      chains), which is responsible for the increase in a- and y-type ion formation.

PMID- 16963277
TI  - Evaluation of binding selectivity of a polyamide probe to single base-pair
      different DNA in A.T-rich region by electrospray ionization mass spectrometry.
AB  - In this study, electrospray ionization mass spectrometry (ESI-MS) was used for
      the evaluation of the binding selectivity of a polyamide probe to single-base
      pair different DNA in an A.T-rich region. In this procedure, DeltaIr(dsn) was
      introduced as a parameter to compare the binding affinities of the polyamides
      with the duplex DNA. The results show that ESI-MS is a very useful tool for
      analysis of binding selectivity of a polyamide probe to single-base pair
      different DNA.

PMID- 16963278
TI  - Visualizing density maps with UCSF Chimera.
AB  - We describe methods for interactive visualization and analysis of density maps
      available in the UCSF Chimera molecular modeling package. The methods enable
      segmentation, fitting, coarse modeling, measuring and coloring of density maps
      for elucidating structures of large molecular assemblies such as virus particles,
      ribosomes, microtubules, and chromosomes. The methods are suitable for density
      maps with resolutions in the range spanned by electron microscope single particle
      reconstructions and tomography. All of the tools described are simple, robust and
      interactive, involving computations taking only seconds. An advantage of the UCSF
      Chimera package is its integration of a large collection of interactive methods.
      Interactive tools are sufficient for performing simple analyses and also serve to
      prepare input for and examine results from more complex, specialized, and
      algorithmic non-interactive analysis software. While both interactive and non
      interactive analyses are useful, we discuss only interactive methods here.

PMID- 16963279
TI  - Simulation analysis of interference EMG during fatiguing voluntary contractions.
      Part I: What do the intramuscular spike amplitude-frequency histograms reflect?
AB  - Decline in amplitude of EMG signals and in the rate of counts of intramuscularly
      recorded spikes during fatigue is often attributed to a progressive reduction of
      the neural drive only. As a rule, alterations in intracellular action potential
      (IAP) are not taken into account. To test correctness of the hypothesis, the
      effect of various discharge frequency patterns as well as changes in IAP shape
      and muscle fibre propagation velocity (MFPV) on the spike amplitude-frequency
      histogram of intramuscular interference EMG signals were simulated and analyzed.
      It was assumed that muscle was composed of four types of motor units (MUs): slow
      twitch fatigue resistant, fast-twitch fatigue resistant, fast intermediate, and
      fast fatigable. MFPV and IAP duration at initial stage before fatigue as well as
      their changes differed for individual MU types. Fatigability of individual MU
      types in normal conditions as well as in the case of ischaemic or low oxygen
      conditions due to restricted blood flow was also taken into account. It was found
      that spike amplitude-frequency histogram is poorly sensitive to MU firing
      frequency, while it is highly sensitive to IAP profile lengthening. It is
      concluded that spike amplitude-frequency analysis can hardly provide a correct
      measure of MU rate-coding pattern during fatigue.

PMID- 16963280
TI  - Simulation analysis of interference EMG during fatiguing voluntary contractions.
      Part II--changes in amplitude and spectral characteristics.
AB  - Capabilities of amplitude and spectral methods for information extraction from
      interference EMG signals were assessed through simulation and preliminary
      experiment. Muscle was composed of 4 types of motor units (MUs). Different
      hypotheses on changes in firing frequency of individual MUs, intracellular action
      potential (IAP) and muscle fibre propagation velocity (MFPV) during fatigue were
      analyzed. It was found that changes in amplitude characteristics of interference
      signals (root mean square, RMS, or integrated rectified value, IEMG) detected by
      intramuscular and surface electrodes differed. RMS and IEMG of surface detected
      interference signals could increase even under MU firing rate reduction and
      without MU synchronisation. IAP profile lengthening can affect amplitude
      characteristics more significantly than MU firing frequency. Thus, an increase of
      interference EMG amplitude is unreliable to reflect changes in the neural drive.
      The ratio between EMG amplitude and contraction response can hardly characterise
      the so-called 'neuromuscular efficiency'. The recently proposed spectral fatigue
      indices can be used for quantification of interference EMG signals. The indices
      are practically insensitive to MU firing frequency. IAP profile lengthening and
      decrease in MFPV enhanced the index value, while recruitment of fast fatigable
      MUs reduced it. Sensitivity of the indices was higher than that of indices
      traditionally used.

PMID- 16963281
TI  - Effect of initial fMRI data modeling on the connectivity reported between brain
      areas.
AB  - Nearly all neuroimaging data analysis rests upon some form of variance
      partitioning. Conventional analyses, with a general linear model (GLM), partition
      the variance in the measured response variable into partitions described by a
      design matrix of explanatory variables. This approach can also be adopted in the
      initial modeling of the data in studies using data-led methods to summarize
      functional connectivity, such as principle component analysis, or studies of
      effective connectivity, using for example structural equation modeling. The point
      made in this technical note is that the partition of the original time series has
      to be precisely described to qualify the sources of variations that are taken
      into account. For conventional analyses using the GLM, the partition investigated
      corresponds to the subspaces of the design matrix that are tested. However, in
      the analyses of functional and effective connectivity, the particular subspaces
      considered are not always specified explicitly. Here we show that selecting
      different subspaces, or variance partitions, can have a profound effect, both
      qualitatively and quantitatively, on the sample covariances and the ensuing
      inferences about connectivity. We will illustrate this using simulated data that
      include condition and block-related effects and their interactions. We will use
      these three subspaces to show how the correlation between two voxels depends on
      which sub-partitions are examined. We will also show how the partition of the
      design matrix influences the resulting correlation matrix observed when studying
      correlations between error terms. We will finally demonstrate, quantitatively,
      the effect of the variance partitions considered on the correlations between two
      regions using a real fMRI study of biological motion.

PMID- 16963282
TI  - How metaphors influence semantic relatedness judgments: the role of the right
      frontal cortex.
AB  - We used event-related fMRI (ER-fMRI) to test the hypothesis that metaphors bias
      cognitive processing of semantic relatedness towards a search for a wider range
      of associations. Twelve right-handed male volunteers read a mixture of metaphoric
      and literal sentences, each sentence being followed by a single word, which could
      be semantically related or not to the preceding sentence context. We found that
      judging unrelated words as contextually irrelevant was associated with increased
      blood oxygenation level-dependent (BOLD) signal in the right ventrolateral
      prefrontal cortex in the metaphoric but not in the literal condition. The same
      region was also activated when subjects endorsed a semantic relation between
      words and metaphoric sentence primes but not between words and literal sentence
      primes. We argue that these results are consistent with the notion of semantic
      open-endedness, whereby figurative statements bias cognitive processing towards a
      search for a wider range of semantic relationships compared to literal
      statements, and thus lend further support to the view that coarse semantic coding
      occurs preferentially in the right hemisphere.

PMID- 16963283
TI  - Digit displacement, not object compliance, underlies task dependent modulations
      in human corticomuscular coherence.
AB  - Human sensorimotor EEG shows oscillatory activity at approximately 10 and
      approximately 20 Hz; the latter frequency is coherent with contralateral EMG. The
      functional significance of this activity is obscure. A recent study found that
      corticomuscular coherence varied systematically with increasing lever compliance
      during a precision grip task. However, since subjects exerted the same force in
      all conditions, changes in lever compliance also produced changes in how far the
      digits moved. In this study, we disambiguated whether corticomuscular coherence
      modulates with object compliance or digit displacement. Subjects performed a
      precision grip task. Under computer control, the manipulandum could simulate a
      load of arbitrary compliance (spring constant). Subjects were required to produce
      a hold-ramp-hold profile of lever displacement, under visual feedback. Subjects
      first performed tasks with different sized lever movements, against an isotonic
      load (zero spring constant). Corticomuscular coherence was calculated between
      left sensorimotor EEG and EMG from five right hand and forearm muscles during the
      hold phase of the task. Coherence magnitude showed a clear dependence on the
      extent of digit displacement. In the next task, lever compliance instantaneously
      changed at the onset of the second hold phase of the task. Corticomuscular
      coherence modulated not with lever compliance during the analysed hold phase, but
      with digit displacement during the preceding ramp movement. These data suggest
      that human corticomuscular coherence is directly related to digit displacement
      during the preceding movement and not to object compliance. We speculate that
      corticomuscular coherence may reflect a sensorimotor recalibration, providing
      updated information about system state following movement.

PMID- 16963284
TI  - Biomechanics of coracoacromial arch modification.
AB  - Although the biomechanics of the coracoacromial arch and coracoacromial ligament
      (CAL) morphology are well studied, to our knowledge, the biomechanics of the
      coracoacromial arch after CAL resection and medial reattachment have not yet been
      studied. The purpose of this report is to examine the biomechanical consequences
      of coracoacromial arch alteration and subsequent reconstruction in cadaveric
      specimens. Anterosuperior humeral head translation was measured after the
      application of an anterosuperior 150-N load under 5 sequential scenarios: (1)
      intact CAL, (2) subperiosteal CAL release, (3) standard acromioplasty, (4) CAL
      reconstruction, and (5) modified Neer acromioplasty. A significant decrease in
      anterosuperior migration was found after CAL reconstruction compared with both
      anterior acromioplasty (P = .038) and modified Neer acromioplasty (P = .01).
      Thus, in patients with massive rotator cuff tears, reconstruction of the CAL may
      provide the necessary stabilizing force to prevent excessive anterosuperior
      translation and possible humeral head escape from the coracoacromial arch.

PMID- 16963285
TI  - The inferior glenohumeral ligament: a correlative investigation.
AB  - The inferior glenohumeral ligament (IGHL) was investigated by correlating the
      biomechanical properties, biochemical composition, and histologic morphology of
      its 3 anatomic regions (superior band, anterior axillary pouch, and posterior
      axillary pouch) in 8 human cadaveric shoulders. The overall biochemical
      composition of the IGHL appeared similar to other ligaments, with average water
      content of 80.9 +/- 2.5%, collagen content of 80.0 +/- 9.2%, and crosslinks of
      0.715 +/- 0.13 mol/mol collagen. The proteoglycan content was highest in the
      superior band (2.73 +/- 0.7 mg/g dry weight) and may, in part, explain its
      viscoelastic behavior. Histologic analysis demonstrated longitudinally organized
      fiber bundles that were more uniform in the mid-substance but more interwoven and
      less uniformly oriented near the insertion sites. The superior band had the most
      pronounced fiber bundle interweaving, while crimping was more evident in the
      anterior axillary pouch. Elastin was identified in each of the regions. Tensile
      testing demonstrated a trend toward higher ultimate tensile stress (16.9 +/- 7.9
      MPa) and tensile modulus (130.3 +/- 47.9 MPa) in the superior band compared to
      the axillary pouch. The mean ultimate tensile strain of the IGHL was 16.8 +/-
      4.6%. These complex IGHL properties may help to explain its unique functions in
      stabilizing the shoulder in different arm positions and at different rates of
      loading, including the failure patterns seen clinically, as in Bankart lesions
      (insertion site) versus capsular stretching (ligament substance).

PMID- 16963286
TI  - Single-incision repair of acute distal biceps ruptures by use of suture anchors.
AB  - The purpose of this study is to report the results of a single limited-incision
      technique for repair of acute distal biceps ruptures by use of suture anchors.
      Sixty consecutive patients underwent distal biceps repair after an acute rupture
      between January 1997 and January 2001 by use of a limited antecubital incision
      and suture anchors. Fifty-three patients could be evaluated at a mean follow-up
      of 38.1 months. A limited transverse incision was made in the antecubital fossa.
      The retracted biceps tendon end was identified, retrieved, and lightly debrided.
      Two suture anchors were placed in the radial tuberosity, and the tendon was
      reapproximated. Final follow-up consisted of physical examination, radiographs,
      and Andrews-Carson elbow score tabulations. According to the Andrews-Carson
      scores, there were 46 excellent and 7 good results. In 2 patients, heterotopic
      ossification developed that resulted in a mild loss of forearm rotation and mild
      pain. In 1 patient, a temporary radial nerve palsy developed, which resolved
      completely within 8 weeks. Repair of acute distal biceps tears via a limited
      antecubital incision and suture anchors is a safe, effective technique.

PMID- 16963287
TI  - Tendinosis of the extensor carpi radialis brevis: an evaluation of three methods
      of operative treatment.
AB  - Many procedures have been described for treating lateral epicondylitis with good
      success. The purpose of this report is to compare 3 operative methods for
      treatment of recalcitrant lateral epicondylitis-open, arthroscopic, and
      percutaneous. All patients with lateral epicondylitis who were operated on over a
      7-year period were retrospectively reviewed. A minimum of 3 months of
      conservative care before surgery had failed in these patients, and they had a
      minimum of 2 years of follow-up. Concomitant pathology, complications, and
      necessary further care were noted. The outcomes were evaluated preoperatively and
      postoperatively with the Andrews-Carson score and visual analog scale scores for
      pain at rest, worst pain, and pain with activity. We included 109 patients in the
      study: 24 percutaneous, 44 arthroscopic, and 41 open procedures. The mean
      duration of conservative care was 13.2 months, including 2.5 conservative
      measures and 1.35 cortisone injections. The mean follow-up was 47.8 months. The
      preoperative Andrews-Carson score was 160.3. The postoperative Andrews-Carson
      score was 195. There was a statistically significant difference between
      preoperative and postoperative Andrews-Carson scores for each of the groups.
      There were no significant differences among the populations regarding age,
      gender, dominance, conservative measures used, cortisone injections, recurrences,
      complications, failures, visual analog scale scores, and preoperative and
      postoperative Andrews-Carson scores. In addition, no difference in outcome scores
      was noted when intraarticular and concomitant pathology was addressed in
      comparison to the population in which tendinosis alone was addressed. Open,
      arthroscopic, and percutaneous treatments of lateral epicondylitis offer 3 highly
      effective ways for the clinician to address this common clinical problem.

PMID- 16963288
TI  - Ulnar nerve neurapraxia in the presence of instability and anomalous ossicles at
      the elbow: a case report.

PMID- 16963289
TI  - Coonrad-Morrey total elbow replacement for primary and revision surgery: a 2- to
      7.5-year follow-up study.
AB  - In this study, 23 patients were treated with the Coonrad-Morrey total elbow
      prosthesis for posttraumatic arthrosis (15 cases), acute distal humeral fracture
      (1 case), inflammatory arthritis (3 cases), and revision of another type of total
      elbow prosthesis (4 cases). After a mean follow-up of 4 years (range, 2-7.5
      years) or at revision as a result of loosening or infection, 78% had a
      satisfactory outcome according to the Mayo Elbow Performance Score. Of the
      patients, 16 (70%) had no or mild pain and 7 had moderate to severe pain. The
      loosening rate was 17%. Possible risk factors for loosening were poor cementing
      and anterior coronoid impingement. Of the patients, 10 (43%) had complications
      and 7 of these (30%) required revision surgery. The Coonrad-Morrey total elbow
      prosthesis can lead to successful outcomes for difficult elbow pathologies.
      However, the complication rate was higher in our series than previously reported.
      Some technical aspects for use of this implant are outlined.

PMID- 16963290
TI  - Effects of overexpression of Sim2 on spatial memory and expression of synapsin I
      in rat hippocampus.
AB  - The single-minded 2 gene (Sim2) plays a crucial role in the mental retardation of
      Down Syndrome (DS). To explore how Sim2 influences spatial memory, a DNA plasmid
      encoding mouse Sim2 (mSim2) wrapped with liposome was bilaterally injected into
      the hippocampus of rats. The effect of overexpressing mSim2 on spatial learning
      was determined by a Morris water maze task. The expression of synapsin I was
      detected by reverse transcriptional-polymerase chain reaction (RT-PCR) analysis
      and immunohistochemistry, respectively. The phosphosynapsin was also examined by
      immunohistochemistry. As demonstrated by RT-PCR, mSim2 was overexpressed in the
      hippocampus of rats, and pcDNA3/mSim2-transfected rats showed longer latency to
      find the hidden platform compared with pcDNA3-transfected rats (P<0.05). Synapsin
      I mRNA and protein expression were decreased significantly by mSim2 transfection,
      as demonstrated by RT-PCR and immunohistochemistry. Moreover, the expression
      profile of phosphosynapsin was similar to that of synapsin I. So it is concluded
      that Sim2 could impair the ability of learning and memory by inhibiting synaptic
      plasticity, and may play a crucial role in the pathogenesis of DS.

PMID- 16963291
TI  - Acute leriche syndrome due to paradoxical embolism.
AB  - Paradoxical embolism, describing the passage of venous or right-sided cardiac
      thrombus into the arterial or systemic circulation through patent foramen ovale,
      is an uncommon cause of acute arterial occlusion. Here, we report acute Leriche
      syndrome in a young woman attributable to paradoxical embolism. Ischaemia, patent
      foramen ovale, and venous thrombosis were the triad of evidence for paradoxical
      embolism.

PMID- 16963292
TI  - Relationship between polymorphisms in thrombophilic genes and preeclampsia in a
      Brazilian population.
AB  - The purpose of this study was to evaluate the thrombophilic genes in pregnant
      women with and without preeclampsia independently or in combination. In a
      prospective case-control study, we investigated four polymorphisms in
      thrombophilic genes in 75 women with mild or severe preeclampsia and 145 women
      with normal pregnancy. The genotype frequencies were assessed and the odds ratio
      (OR) calculated. When we analyzed the polymorphisms independently and the
      development of preeclampsia, no association was observed
      [methylenetetrahydrofolate reductase (MTHFR) 677TT genotype, OR 2.07, 95%
      confidence interval (CI) 0.99-4.30; prothrombin mutation (F II) (GA or AA
      genotypes) OR 8.11, 95% CI 0.89-73.92; factor V Leiden (FV Leiden) OR 3.94, 95%
      CI 0.35-44.23; plasminogen activator inhibitor (PAI-1) 4G/4G genotype, OR 1.63,
      95% CI 0.87-3.05] not even with severe preeclampsia subgroup analysis. However,
      when we investigated a possible interaction among these polymorphisms on the
      development of the preeclampsia, the OR for having one risk genotype, one or two
      genotype risk factors and two genotype risk factors compared to those without
      genotype risk factors were 1.97 (95% CI 1.08-3.59), 2.21 (95% CI 1.25-3.92) and
      4.27 (95% CI 1.3-13.9), respectively. In conclusion, in the population analyzed,
      the presence of the genotype risk factors alone does not seem to be associated
      with the development of preeclampsia even in the severe presentation form.
      However, an interaction among the MTHFR, F II, FV and PAI-1 gene polymorphisms on
      the development of the preeclampsia was indicated.

PMID- 16963294
TI  - The volume and hydration of the Cryptococcus neoformans polysaccharide capsule.
AB  - We present a new method to measure capsule size in the human fungal pathogen
      Cryptococcus neoformans that avoids the limitations and biases inherent in India
      ink measurements. The method is based on the use of gamma-radiation, which
      efficiently releases the capsule from the cell. By comparing the volume of
      irradiated and non-irradiated cells, one can accurately estimate the relative
      size of the capsule per cell. This method was also used to obtain an estimate of
      the capsule weight and water content. The C. neoformans capsule is a highly
      hydrated structure in all the conditions measured. However, after capsule
      enlargement, the amount of capsular polysaccharide significantly increases,
      suggesting a that capsule growth has a high energy cost for the cell.

PMID- 16963293
TI  - Insomnia and its treatment in women with breast cancer.
AB  - Insomnia is a common complaint in breast cancer patients and has been shown to
      have a host of psychological and medical correlates and consequences. Typically
      insomnia is treated pharmacologically, however more recent findings from
      randomized controlled clinical trials support the use of cognitive behavioral
      therapies. The aim of this article is to review the empirically supported breast
      cancer literature on insomnia, briefly present and explain the insomnia treatment
      options available, and extrapolate research guidelines for future directions in
      this growing field. Behavioral therapeutic approaches for insomnia seem
      particularly suitable to use in the breast cancer populations because they have
      lower risk of interacting with the cancer treatment, do not burden the patients
      with additional pharmacological treatments, and can target the treatment towards
      ameliorating specific symptoms, like fatigue, that are characteristic in this
      population. However, there is a need for replication of efficacy studies of
      cognitive behavioral treatments for insomnia in breast cancer, as well as studies
      investigating vulnerability, risk and protective factors that might ultimately
      lead to insomnia prevention programs for use in this population.

PMID- 16963295
TI  - Bayesian and information theory analysis of MAS sideband patterns in spin 1/2
      systems.
AB  - Bayesian statistics and information theory are used to analyze the reliability of
      extracting chemical shift parameters from spinning sideband patterns of spin 1/2
      systems. Efficient code has been written to calculate the two-dimensional
      posterior probability as a function of the chemical shift anisotropy, delta, and
      the asymmetry parameter, eta, given the sideband intensities and the signal-to
      noise ratio. This method has the advantage of assuming only that the noise in the
      sideband intensities is distributed as a Gaussian. It assumes nothing about the
      distribution of the values of parameters delta and eta, which are shown in some
      cases to be highly non-Gaussian. The utility of Bayesian analysis is demonstrated
      on 1D slow-spinning MAS spectra and on sideband patterns extracted from 2D PASS
      spectra. Previous investigations have shown that there is an optimal range of
      spinning frequencies for determining delta. In this study, information theory is
      used to determine the signal-to-noise ratio dependence of the entropy in delta,
      eta, and total entropy in spinning sideband spectra. The entropy is a measure of
      the information content of a probability distribution. When the entropy is zero,
      there is perfect information on a system, while if it is infinite, there is no
      information on the system. It is found that for all values of eta and for signal
      to-noise ratios in the range 50-1000, an entropy minimum in nudelta/nur occurs
      for values 1.5<or=nudelta/nur<or=3. In the same range of signal-to-noise ratios,
      the entropy in eta is a monotonically decreasing function of nudelta/nur. The
      global information content of a spinning sideband pattern (i.e., the total
      entropy) is dependent on the signal-to-noise ratio and has an optimal value at
      nudelta/nur approximately 2 at a signal-to-noise ratio of 50 and increasing to
      approximately 2.5 for signal-to-noise ratios of 1000. Finally, the increase of
      information in a sideband pattern as a function of the number of sidebands used
      in the analysis is examined. Most of the information about delta and eta is
      contained in the five central sidebands; i.e., sidebands -2 to 2.

PMID- 16963296
TI  - How accurately can the diffusion profiles indicate multiple fiber orientations? A
      study on general fiber crossings in diffusion MRI.
AB  - The q-space imaging techniques and high angular resolution diffusion (HARD)
      imaging have shown promise to identify intravoxel multiple fibers. The measured
      orientation distribution function (ODF) and apparent diffusion coefficient (ADC)
      profiles can be used to identify the orientations of the actual intravoxel
      fibers. The present study aims to examine the accuracy of these profile-based
      orientation methods by comparing the angular deviations between the estimated
      local maxima of the profiles and the real fiber orientation for a fiber crossing
      simulated with various intersection angles under different b values in diffusion
      weighted MRI experiments. Both noisy and noise-free environments were
      investigated. The diffusion spectrum imaging (DSI), q-ball imaging (QBI), and
      HARD techniques were used to generate ODF and ADC profiles. To provide a better
      comparison between ODF and ADC techniques, the phase-corrected angular deviations
      were also presented for the ADC method based on a circular spectrum mapping
      method. The results indicate that systematic angular deviations exist between the
      actual fiber orientations and the corresponding local maxima of either the ADC or
      ODF profiles. All methods are apt to underestimation of acute intersection and
      overestimation of obtuse intersection angle. For a typical slow-exchange fiber
      crossing, the ODF methods have a non-deviation zone around the 90 degrees
      intersection. Before the phase-correction, the deviation of ADC profiles
      approaches a peak at the 90 degrees intersection, while after the correction the
      ADC deviations are significantly reduced. When the b factor is larger than 1000
      s/mm2, the ODF methods have smaller angular deviations than the ADC methods for
      the intersections close to 90 degrees . QBI method demonstrates a slight yet
      consistent advantage over the DSI method under the same conditions. In the noisy
      environment, the mean value of the deviation angles shows a high consistency with
      the corresponding deviation in the nose-free condition.

PMID- 16963297
TI  - Structural determination of the oligosaccharides in the milk of an Asian elephant
      (Elephas maximus).
AB  - Milk of an Asian elephant (Elephas maximus), collected at 11 days post partum,
      contained 91 g/L of hexose and 3 g/L of sialic acid. The dominant saccharide in
      this milk sample was lactose, but it also contained isoglobotriose (Glc(alpha1
      3)Gal(beta1-4)Glc) as well as a variety of sialyl oligosaccharides. The sialyl
      oligosaccharides were separated from neutral saccharides by anion exchange
      chromatography on DEAE-Sephadex A-50 and successive gel chromatography on Bio Gel
      P-2. They were purified by high performance liquid chromatography (HPLC) using an
      Amide-80 column and characterized by 1H-NMR spectroscopy. Their structures were
      determined to be those of 3'-sialyllactose, 6'-sialyllactose, monofucosyl
      monosialyl lactose (Neu5Ac(alpha2-3)Gal(beta1-4)[Fuc(alpha1-3)]Glc), sialyl lacto
      N-neotetraose c (LST c), galactosyl monosialyl lacto-N-neohexaose, galactosyl
      monofucosyl monosialyl lacto-N-neohexaose and three novel oligosaccharides as
      follows: Neu5Ac(alpha2-3)Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1-3)Gal(beta1
      4)Glc, Neu5Ac(alpha2-6)Gal(beta1-4)GlcNAc(beta1-3)Gal(beta1-4)GlcNAc(beta1
      3)Gal(beta1-4)Glc, and Neu5Ac(alpha2-3)Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1
      3)Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1-3)Gal(beta1-4)Glc. The higher
      oligosaccharides contained only the type II chain (Gal(beta1-4)GlcNAc); this
      finding differed from previously published data on Asian elephant milk
      oligosaccharides.

PMID- 16963298
TI  - Does overfeeding enhance genotype effects on liver ability for lipogenesis and
      lipid secretion in ducks?
AB  - We evaluated the effects of genotype (Muscovy, Pekin and their crossbreed hinny
      and mule ducks) and feeding levels (overfeeding between 12 and 14 weeks of age vs
      ad libitum feeding) on liver ability for lipogenesis and lipid secretion in
      ducks. Samples of liver and blood were collected at 14 weeks of age from 8 birds
      per group. Plasma levels of insulin was considerably increased in overfed ducks
      (1.9-fold), stimulating the hepatic activity of the main enzymes involved in
      lipogenesis from glucose (glucokinase, GK, glucose-6-phosphate dehydrogenase,
      G6PDH, malic enzyme, ME, acetyl CoA carboxylase, ACX), while cytochrome-c oxidase
      (COX) activity, indicating overall oxidation ability of energy-yielding
      substrates, remained unchanged. Plasma levels of triglycerides, phospholipids and
      total cholesterol were therefore increased (1.9, 3.7, 1.6 and 1.6-fold,
      respectively). Glycaemia also significantly increased (+8%). Pekin ducks
      exhibited higher levels of GK and G6PDH activity in the liver than Muscovy ducks,
      suggesting a greater ability to use glucose consistent with their lower
      glycaemia. Muscovy ducks had greater ACX activity, suggesting greater ability to
      synthesise lipids. However, plasma lipid levels were much higher in Pekin ducks
      than in Muscovy ducks, suggesting a greater ability to export lipids from the
      liver. Values for the different criteria measured in this study were intermediate
      or similar in hinny and mule ducks to those of parental species. The high values
      for GK, G6PDH, ME and ACX activity in hybrid ducks enabled them to produce heavy
      fatty livers with the same chemical and lipid composition as Muscovy ducks and
      characterised by high amounts of triglycerides (around 96% of total lipids), and
      saturated and mono-unsaturated fatty acids.

PMID- 16963299
TI  - Molecular structure and expression patterns of flounder (Paralichthys olivaceus)
      Myf-5, a myogenic regulatory factor.
AB  - Myf-5, a member of the myogenic regulatory factors (MRF), has been shown to be
      expressed in muscle precursors in early stage zebrafish embryos. The MRFs,
      including MyoD, Myf-5, Myogenin and MRF4, belong to the basic Helix-Loop-Helix
      transcription factors that contain a conserved basic Helix-Loop-Helix (bHLH)
      domain. To better understand the role of Myf-5 in the development of fish
      muscles, we have isolated the Myf-5 genomic sequence and cDNA from Flounder
      (Paralichthys olivaceus), and analyzed its structures and patterns of expression.
      Promoter analysis identified several putative transcription factor binding sites
      such as an E-box, NF-Y sites that might confer muscle-specific expression. Myf-5
      transcripts were first detected in the paraxial mesoderm that gives rise to slow
      muscles. During somitogenesis, Myf-5 expression was found in developing somites.
      Myf-5 expression decreased gradually in somites in the anterior region, but
      remained strong in the newly formed somites. In the hatching stage, the
      expression was also detected in other muscle cells such as head muscle and fin
      muscle. In the growing fish, RT-PCR results showed that Myf-5 was expressed in
      the skeletal muscle and intestine.

PMID- 16963300
TI  - A patient with arginase deficiency and episodic hyperammonemia successfully
      treated with menses cessation.
AB  - Arginase deficiency is an urea cycle disorder that generally presents with mental
      retardation and spasticity, yet uncommonly with episodes of hyperammonemia. A
      female adolescent with arginase deficiency developed hyperammonemic episodes
      temporally related to her menstrual cycle, which ceased upon adequate treatment
      with depot medroxy progesterone acetate. A similar case was previously reported.
      A catamenial trigger should be considered in adolescent female arginase-deficient
      patients with episodes of hyperammonemia.

PMID- 16963301
TI  - Levels of anti-M2 and anti-beta1 autoantibodies do not correlate with the degree
      of heart dysfunction in Chagas' heart disease.
AB  - Chronic chagasic cardiomyopathy (CCC) is characterized mainly by a dilated
      cardiomyopathy complicated by frequent and complex ventricular arrhythmias and/or
      conduction defects. The aim of the present study was to evaluate functional
      implications of neurotransmitter receptor autoantibodies in vivo. Sera from
      chagasic patients were used to measure the level of autoantibodies to peptide
      fragments from the M2 cholinergic and beta1 adrenergic receptors. Optical density
      values and the frequency of anti-M2 and anti-beta1 antibodies were significantly
      higher in the indeterminate form and in CCC patients than in normal individuals.
      There was no correlation between levels of autoantibodies and clinical parameters
      of ventricular dysfunction, as assessed by echocardiography. Patients presenting
      with chronotropic insufficiency in exercise test had higher levels of anti-M2 but
      not anti-beta1 autoantibodies. Although anti-M2 and anti-beta1 antibodies do not
      appear to play a role in the pathophysiology of the heart failure that
      accompanies severe CCC, anti-M2 cholinergic autoantibodies may contribute to the
      pathogenesis of Chagas' disease dysautonomia.

PMID- 16963302
TI  - An act of homicide and what it brings to mind: a case presentation.
AB  - There are many views and studies as to the motive, manner, and victim of
      homicide, which is one of the severest forms of violence. The case presented here
      is that of a man who was strangled with a nylon ligature by his prison cellmate
      who later stabbed his victim's eyes with a piece of wood and a nail and slashed
      his face. The study is presented with respect to how the murder was committed and
      how the defendant was evaluated.

PMID- 16963303
TI  - Quantitative RT-PCR assays of hypoxia-inducible factor-1alpha, erythropoietin and
      vascular endothelial growth factor mRNA transcripts in the kidneys with regard to
      the cause of death in medicolegal autopsy.
AB  - Accumulating studies demonstrate that the expressions of hypoxia-inducible factor
      1 (HIF-1), erythropoietin (EPO) and vascular endothelial growth factor (VEGF)
      depend on cellular oxygen tension, which is involved in the pathological process
      of tissue hypoxia and/or ischemia. The present study investigated hypoxia
      inducible factor-1alpha (HIF-1alpha), EPO and VEGF mRNA expressions in the kidney
      with regard to the cause of death in medicolegal autopsy. Relative
      quantifications of HIF-1alpha, EPO and VEGF mRNAs, based on real-time TaqMan
      reverse transcription-polymerase chain reaction (RT-PCR), were performed on
      tissue specimens obtained from consistent sites of the bilateral renal cortices.
      The cases (total, n=245, 6-48h postmortem) included fatal blunt/sharp instrument
      injuries (n=53/31), asphyxia (n=28: aspiration, n=8; strangulation/hanging,
      n=20), drowning (n=27), fire fatality (n=62), acute myocardial
      infarction/ischemia (AMI, n=39), and gastrointestinal hemorrhage (n=5). Both HIF
      1alpha and EPO mRNA levels were significantly lower in drowning cases. More
      characteristic findings were found for VEGF mRNA: it showed higher expression
      levels for AMI, acute blunt/sharp instrument injury, and aspiration, whereas it
      was lower for neck compression (strangulation/hanging), drowning, fire fatality
      with higher blood carboxyhemoglobin (COHb) levels (>60%), peracute blunt injury,
      and gastrointestinal hemorrhage. Quantitative assays of renal HIF-1alpha, EPO and
      VEGF mRNA transcripts are potentially useful for investigating the
      pathophysiology of death, and VEGF mRNA may be especially useful as an indication
      of acute circulatory failure.

PMID- 16963304
TI  - Firearm fatalities in Delhi, India.
AB  - Studies on firearm fatalities in various countries have been published. However,
      pattern and incidence of fatal firearm injuries in Delhi has largely gone
      unreported. This study was taken up with the objective of reporting the pattern
      and incidence of fatal firearm injuries in Delhi and comparing it with the
      pattern seen in other countries. One hundred and seven firearm fatalities
      autopsied during the last 6 years were studied. 46.7% victims were aged between
      20 and 30 years and 90.7% were males; similar findings were seen in other
      countries. 92.6% were victims of homicidal attacks, 6.5% suicidal and 0.9%
      accidental. This is in sharp contrast to the pattern in other countries where
      suicides were the predominant group and homicides accounted for a small number of
      cases. A high presence of illegal country made guns was an explanation for this
      trend. Single firings were the norm. Chest (39%) and head (29.6%) were the two
      most common entry sites for the bullets, a pattern somewhat similar to that of
      other countries. Survival time, cause of death and recovery of projectiles was
      also studied. Elimination of illegal country made guns is of the utmost
      importance in order to curb the high homicidal firearm fatality rate in this
      region.

PMID- 16963305
TI  - Estimation of stature from vertebral column length in South Indians.
AB  - Stature is one of the essential parameters in the establishment of identity of an
      individual. To estimate the stature from different segments of the vertebral
      column, a study was done in the South Indian population. The lengths of different
      segments of the vertebral column were measured along the anterior surface in 72
      males and 45 females. Regression formulae were deduced for each segment in both
      the groups. The correlation coefficient of the estimate ranged from 0.776 to
      0.583 in males and 0.708 to 0.325 in females. The standard error of the estimate
      ranged from 4.38 to 5.65cm in males and 4.16 to 5.58cm in females. This method is
      useful to estimate the stature in cases of highly decomposed, burnt or mutilated
      bodies, where the long bones are not available.

PMID- 16963306
TI  - Genetic data on 10 autosomal STR loci in the Bangladeshi population.
AB  - Allele frequencies of 10 autosomal short tandem repeat (STR) loci, D3S1358, vWA,
      D16S539, D2S1338, D8S1179, D21S11, D18S51, D19S433, TH01 and FGA were determined
      in 211 unrelated Bangladeshi individual using AmpFLSTR SGM Plus PCR Amplification
      Kit. Statistical parameters of forensic importance, the power of discrimination
      (PD), observed and expected heterozygosity values (H), polymorphism information
      content (PIC), probability of match (PM), power of exclusion (PE) and typical
      paternity index (TPI) were calculated for the loci. These parameters indicated
      the usefulness of the loci in paternity testing and personal identification in
      the Bangladeshi population.

PMID- 16963307
TI  - Ethoxylation of p-chloronitrobenzene using phase-transfer catalysts by ultrasound
      irradiation: a kinetic study.
AB  - Ethoxy-4-nitrobenzene was synthesized by the reaction of 4-chloronitrobenzene
      with potassium ethoxide in a homogeneous system using benzyltriethylammonium
      chloride (QCl) as a phase-transfer catalyst at 50 degrees C under ultrasound
      irradiation conditions. The use of phase-transfer catalysts and ultrasound has
      been compared and demonstrated in this nucleophilic substitution reactions. The
      kinetics of the reaction depends on the effect of amount of catalyst, quaternary
      ammonium salts, agitation speed, amount of potassium hydroxide, amount of
      ethanol, temperature and the frequency of the ultrasound waves on the conversion
      of the reaction.

PMID- 16963308
TI  - Gene therapy and transplantation in CNS repair: the visual system.
AB  - Normal visual function in humans is compromised by a range of inherited and
      acquired degenerative conditions, many of which affect photoreceptors and/or
      retinal pigment epithelium. As a consequence the majority of experimental gene-
      and cell-based therapies are aimed at rescuing or replacing these cells. We
      provide a brief overview of these studies, but the major focus of this review is
      on the inner retina, in particular how gene therapy and transplantation can
      improve the viability and regenerative capacity of retinal ganglion cells (RGCs).
      Such studies are relevant to the development of new treatments for ocular
      conditions that cause RGC loss or dysfunction, for example glaucoma, diabetes,
      ischaemia, and various inflammatory and neurodegenerative diseases. However, RGCs
      and associated central visual pathways also serve as an excellent experimental
      model of the adult central nervous system (CNS) in which it is possible to study
      the molecular and cellular mechanisms associated with neuroprotection and axonal
      regeneration after neurotrauma. In this review we present the current state of
      knowledge pertaining to RGC responses to injury, neurotrophic and gene therapy
      strategies aimed at promoting RGC survival, and how best to promote the
      regeneration of RGC axons after optic nerve or optic tract injury. We also
      describe transplantation methods being used in attempts to replace lost RGCs or
      encourage the regrowth of RGC axons back into visual centres in the brain via
      peripheral nerve bridges. Cooperative approaches including novel combinations of
      transplantation, gene therapy and pharmacotherapy are discussed. Finally, we
      consider a number of caveats and future directions, such as problems associated
      with compensatory sprouting and the reformation of visuotopic maps, the need to
      develop efficient, regulatable viral vectors, and the need to develop different
      but sequential strategies that target the cell body and/or the growth cone at
      appropriate times during the repair process.

PMID- 16963309
TI  - Dopaminergic neuroprotection by neurturin-expressing c17.2 neural stem cells in a
      rat model of Parkinson's disease.
AB  - Genetically engineered neural stem cell (NSC) lines are promising vectors for the
      treatment of regenerative diseases, especially Parkinson's disease (PD).
      Neurturin (NTN), a member of the glial cell line-derived neurotrophic factor
      family, has been demonstrated to act specifically on mesencephalic dopaminergic
      neurons, suggesting its therapeutic potential for PD. Here, we have generated a
      NTN-secreting c17.2 NSC line and investigated the protective effect of NTN-c17.2
      on PD rat models. These NTN-releasing NSCs engrafted and integrated in the host
      striatum with good success, gave rise to neurons, astrocytes and
      oligodendrocytes, and maintained stable, high-level NTN expression. In addition,
      inverse transfer of NTN protein into the substantia nigra (SN) was able to
      protect dopaminergic neurons from 6-OHDA toxicity. Observation of rotational
      behavior showed that the NTN group performed significantly better than the Mock
      group, and the protective effect of NTN lasted for at least 4 months. HPLC tests
      indicated that the contents of neurotransmitters (e.g. dopamine) in the corpus
      striatum area of the NTN-c17.2 group and the Mock-c17.2 group were significantly
      higher than in the PBS group, but there was no significant difference between
      expression in the NTN-c17.2 and Mock-c17.2 groups. Taken together, our results
      suggest that transplantation of NTN-secreting NSCs exerted protective on PD rat
      models.

PMID- 16963310
TI  - The validity of clinical measures of patella position.
AB  - Patellar taping is regarded as an important element of the treatment of
      patellofemoral joint pain. Key to the successful use of patellar taping is the
      assessment of patella position. The reliability and validity of the techniques
      used to assess patella position has been questioned. The aim of the study was to
      assess the validity of the clinical assessment technique of patella medio-lateral
      position and patella lateral tilt against the criterion measure of MRI. Twenty
      four subjects eight females and 16 males had their patella position examined in
      the study (mean age 24.5+/-7.9 years, range 18-42 years). The study also assessed
      intra-tester reliability of the technique. A good correlation was found between
      the findings of the clinical test for medio-lateral position and the MRI measure
      (r=0.611, p=0.002). All of the subjects found to have a laterally tilted patella
      on clinical examination had a lateral patella tilt defined by PTA of greater than
      5 degrees . Those subjects with a PTA of less than 5 degrees on clinical
      examination were assessed as having no degree of patella tilt. The study
      undertaken shows that when undertaken by an experienced manual therapist
      positional assessment of the patella can have strong criterion validity and intra
      tester reliability.

PMID- 16963311
TI  - The development and use of mass media interventions for health-care messages
      about back pain: what do members of the public think?
AB  - The study sought to identify and explore the opinions, beliefs and views of
      members of the public regarding the use of media interventions for the delivery
      of health-care messages. It used a draft back pain campaign looking at the level
      of credibility, acceptability and trust in the authority of these messages. Sixty
      eight members of the public participated in the study. A qualitative study design
      was used with semi-structured focus groups and a sampling frame including gender,
      age, socio-economic group, and experience of back pain. Three main themes were
      identified. 1. Media consumption. 2. Credibility. 3. Specific issues surrounding
      the proposed sample media campaign. The use of media to provide health-care
      information was viewed positively, with the NHS perceived as the most trustworthy
      source, and Government bodies viewed with scepticism. Issues surrounding the
      language, terminology and tone of campaigns were raised. A closer collaboration
      between health-care professionals and the public is advocated to achieve valuable
      and effective media campaigns.

PMID- 16963312
TI  - Postural neck pain: an investigation of habitual sitting posture, perception of
      'good' posture and cervicothoracic kinaesthesia.
AB  - Impairments of cervico-cephalic kinaesthesia and habitual forward head posture
      have been considered important in the aetiology of postural neck pain, yet these
      factors have not been specifically examined in a homogeneous clinical population.
      The objective of this study was to compare the habitual sitting posture (HSP),
      perception of good posture and postural repositioning error (PRE) of the cervico
      thoracic (CT) spine in individuals with postural neck pain, with a matched group
      of asymptomatic subjects. Twenty-one subjects with postural neck pain and 22
      asymptomatic control subjects were recruited into the study. An optical motion
      analysis system was used to measure the HSP and perceived 'good' sitting posture.
      PRE was measured over six trials where the subject attempted to replicate their
      self-selected 'good' posture. There was no difference between the groups in the
      HSP but significant differences were identified in the perception of 'good'
      posture. Posture repositioning error was higher for the head posture variables
      than for CT and shoulder girdle variables in both groups. However, there was no
      significant difference in posture repositioning error between groups for any of
      the posture measures. The findings suggest that individuals with postural neck
      pain may have a different perception of 'good' posture, but no significant
      difference in HSP or kinaesthetic sensibility compared with matched asymptomatic
      subjects.

PMID- 16963313
TI  - Human malignant mesothelioma: molecular mechanisms of pathogenesis and
      progression.
AB  - The continuing identification and elucidation of the molecular defects involved
      in mesothelioma pathogenesis and progression should lead to better disease
      control and greater therapeutic options in the near future. Goal of this review
      article is to summarize the most recent advances in molecular pathogenesis of
      mesothelioma and discuss possible therapeutic implications of these findings.

PMID- 16963314
TI  - Cytokeratin-7, cytokeratin-19, and c-Kit: Immunoreaction during the evolution
      stages of primary biliary cirrhosis.
AB  - AIMS: The quantitative and qualitative expression of CK-7, CK-19, and c-Kit
      markers in various cell types were evaluated during the four stages of primary
      biliary cirrhosis. METHODS: A total of 53 specimens were examined. Thirteen
      specimens were identified as Ludwig's stage 1, 23 as stage 2, 14 as stage 3, and
      2 as stage 4. Immunohistochemical stains were performed for CK-7, CK-19, c-Kit
      and subsequently graded. The cell types expressing the markers were qualitatively
      analysed. RESULTS: In normal liver, biliary epithelial cells expressed CK-7, CK
      19, whereas the Canals of Hering (CoH) were stained with c-Kit and partly CK-19,
      contrary to hepatocytes. The aforementioned expression patterns were detected in
      pathologic samples of PBC, with qualitative and quantitative differences though.
      CK-7 grading was found to correspond with Ludwig's staging, in contrast to CK-19.
      c-Kit was absent in the early stages and focally present in the advanced stages.
      All biliary-type, intermediate cells and hepatocytes were CK-7 positive,
      particularly in samples with cholestasis, whereas CK-19 was only found in biliary
      type and intermediate cells. c-Kit was expressed in CoH which appeared as
      clusters and strings of cuboidal cells in advanced stages. CONCLUSIONS: CK-7 can
      be regarded as a histological marker of progression in PBC; CK-19 cannot be
      assessed as a safe marker in the development of the disease. The absence of c-Kit
      in the early stages of PBC is related to the destruction of the CoH. CK-7
      hepatocyte expression in the advanced stages is likely to be related to damaged
      hepatocytes' metaplastic potential.

PMID- 16963315
TI  - Clinical experience in cell-based therapeutics: disc chondrocyte transplantation
      A treatment for degenerated or damaged intervertebral disc.
AB  - Disc herniation treated by discectomy results in a significant loss of nucleus
      material and disc height. Biological restoration through the use of autologous
      disc chondrocyte transplantation offers a potential to achieve functional
      integration of disc metabolism and mechanics. Chondrocytes that have been removed
      from damaged cartilaginous tissues maintain a capacity to proliferate, produce
      and secrete matrix components and respond to physical stimuli such as dynamic
      loading. Nucleus regeneration using autologous cultured disc-derived chondrocytes
      (ADCT) has been demonstrated in a canine model and in clinical pilot studies. In
      2002 a prospective, controlled, randomised, multi-center study, EuroDISC,
      comparing safety and efficacy of autologous disc chondrocyte transplant,
      chondrotransplant DISC, plus discectomy (ADCT), with discectomy alone was
      initiated. A dog model was used to investigate the hypothesis that autologous
      disc chondrocytes can be used to repair damaged intervertebral disc. Disc
      chondrocytes were harvested and expanded in culture under controlled and defined
      conditions, returned to the same animals from which they had been sampled
      (autologous transplantation) via percutaneous delivery. The animals were analyzed
      at specific times after transplantation by several methods to examine whether
      disc chondrocytes integrated with the surrounding tissue, produced the
      appropriate intervertebral disc extracellular matrix, and might provide a
      formative solution to disc repair. The clinical goals of the EuroDISC study, were
      to provide long-term pain relief, maintain disc height and prevent adjacent
      segment disease. Interim analysis was performed after 2 years; Oswestry (low back
      pain/disability), Quebec Back-Pain Disability Scale, as well as Prolo and VAS
      score were used for the evaluation. Disc height was assessed by MRI. In the
      context of degenerative changes in an injury model: () autologous disc
      chondrocytes were expended in culture and returned to the disc by a minimally
      invasive procedure after 12 weeks; () disc chondrocytes remained viable after
      transplantation as shown by bromodeoxyuridine incorporation and maintained a
      capacity for proliferation after transplantation as depicted by histology; ()
      transplanted disc chondrocytes produced an extracellular matrix that displayed
      composition similar to normal intervertebral disc tissue. Positive evidence of
      Proteoglycan content was supported by accepted histochemical staining techniques
      such as Safranin O-Fast Green; () both Type II and Type I collagens were
      demonstrated in the regenerated intervertebral disc matrix by
      immunohistochemistry after chondrocyte transplantation; and () when the disc
      heights were analyzed for variance according to treatment a statistically
      significant-correlation between transplanting cells and retention of disc height
      was achieved. A clinically significant reduction of low back pain in the ADCT
      treated group was shown by all three pain score systems. The median total
      Oswestry score was 2 in the ADCT-treated group compared with 6 in the control
      group. Decreases in the disability index and VAS score in ADCT-treated patients
      correlated strongly with the reduction of low back pain. Decreases in disc height
      over time were only found in the control group, and of potential significance,
      intervertebral discs in adjacent segments appeared to retain hydration when
      compared to those adjacent to levels that had undergone discectomy without cell
      intervention. Autologous chondrocyte transplantation is technically feasible and
      biologically relevant to repairing disc damage and retarding disc degeneration.

PMID- 16963316
TI  - Distribution of the genus Mallomonas (Synurophyceae) - ubiquitous dispersal in
      microorganisms evaluated.
AB  - The neutral dispersal model in protists was suggested as a general principle
      resulting in either cosmopolitan or ecologically restricted distribution of
      individual species. The high local diversity results in "flat" species-area
      curves of individual protist groups. We investigated the local and regional
      diversity of the genus Mallomonas in the alluvial plain of upper Luznice in the
      Czech Republic. About 86.5% of species previously reported from all types of
      freshwater biotopes within the country were found in our investigated localities.
      However, there was a considerable increase of species numbers in relation to the
      total area of available habitats on the continent and global scales. In three
      species found in our localities, the floristic data indicate a possible
      geographically restricted distributional pattern. Here, we discuss possible
      reasons for this phenomenon.

PMID- 16963317
TI  - Self-valued health in Danish women after cervix cancer surgery--A retrospective
      questionnaire study.

PMID- 16963318
TI  - Prediction of protein subcellular location using hydrophobic patterns of amino
      acid sequence.
AB  - The function of eukaryotic protein is closely correlated with its subcellular
      location. The number of newly found protein sequences entering into data banks is
      rapidly increasing with the success of human genome project. It is highly
      desirable to predict a protein subcellular automatically from its amino acid
      sequence. In this paper, amino acid hydrophobic patterns and average power
      spectral density (APSD) are introduced to define pseudo amino acid composition.
      The covariant-discriminant predictor is used to predict subcellular location.
      Immune-genetic algorithm (IGA) is used to find the fittest weight factors which
      are very important in this method. As such, high success rates are obtained by
      both self-consistency test (86%) and jackknife test (73%). More than 80%
      predictive accuracy is achieved in independent dataset test. The results
      demonstrate that the proposed method is practical. And, the method illuminates
      that the protein subcellular location can be predicted from its surface physio
      chemical characteristic of protein folding.

PMID- 16963319
TI  - Toll-like receptor 4-induced cytokine production circumvents protection conferred
      by TGF-beta in coxsackievirus-mediated autoimmune myocarditis.
AB  - Coxsackie B virus (CBV) infections are a leading cause of autoimmune myocarditis
      associated with inflammatory heart disease and sudden death in young adults.
      Previously, we demonstrated that transgenic expression of the immunosuppressive
      cytokine, transforming growth factor-beta (TGF-beta), specifically in the
      pancreas protected otherwise susceptible mice from CBV-mediated autoimmune
      myocarditis. Herein, we demonstrate that macrophages from these transgenic mice
      fail to upregulate the costimulatory molecule CD40 following infection,
      suggesting that pancreatic TGF-beta protects by limiting antigen stimulation. We
      further demonstrate that co-administration of LPS from Salmonella minnesota, a
      Toll-like receptor (TLR)-4 ligand, with CBV infection overcomes protection
      whereas the TLR-2 agonist, LPS from Porphyromonas gingivalis, does not.
      Furthermore, LPS-mediated disease induction correlates with increased levels of
      pro-inflammatory cytokines. Interestingly, the action of LPS (TLR-4) did not
      alter antibody isotype switching, increase viral replication or modulate CD40
      expression. Instead, LPS breaks protection through an alternative mechanism
      specific to TLR-4 signaling.

PMID- 16963321
TI  - FTMS and TOF/TOF mass spectrometry in concert: identifying peptides with high
      reliability using matrix prespotted MALDI target plates.
AB  - In this paper we describe a combination of the mass spectrometric techniques
      MALDI-TOF/TOF and MALDI-FTMS to identify proteins in complex samples using
      prespotted MALDI target plates. By this procedure accurate FTMS mass measurements
      and TOF/TOF data are obtained from the same spot. We have found that this
      combination of techniques leads to more reliable identification of peptides.

PMID- 16963320
TI  - CFTR gene analysis in Latin American CF patients: heterogeneous origin and
      distribution of mutations across the continent.
AB  - BACKGROUND: Cystic Fibrosis (CF) is the most prevalent Mendelian disorder in
      European populations. Despite the fact that many Latin American countries have a
      predominant population of European-descent, CF has remained an unknown entity
      until recently. Argentina and Brazil have detected the first patients around
      three decades ago, but in most countries this disease has remained poorly
      documented. Recently, other countries started publishing their results. METHODS:
      We present a compilation and statistical analysis of the data obtained in 10
      countries (Argentina, Brazil, Chile, Colombia, Costa Rica, Cuba, Ecuador, Mexico,
      Uruguay and Venezuela), with a total of 4354 unrelated CF chromosomes studied.
      RESULTS: The results show a wide distribution of 89 different mutations, with a
      maximum coverage of 62.8% of CF chromosomes/alleles in the patient's sample. Most
      of these mutations are frequent in Spain, Italy, and Portugal, consistent with
      the origin of the European settlers. A few African mutations are also present in
      those countries which were part of the slave trade. New mutations were also
      found, possibly originating in America. CONCLUSION: The profile of mutations in
      the CFTR gene, which reflects the heterogeneity of its inhabitants, shows the
      complexity of the molecular diagnosis of CF mutations in most of the Latin
      American countries.

PMID- 16963322
TI  - A simple peptide mapping method by partial filling micellar electrokinetic
      capillary chromatography with a zwitterionic-nonionic mixed micelle.
AB  - A partial filling micellar electrokinetic capillary chromatography (PF-MEKC)
      method with a mixed micelle system composed of a zwitterionic surfactant named 3
      (N,N-dimethylhexadecylammonium)propanesulfonate (PAPS) and a nonionic surfactant
      polyethylene glycol dodecyl ether (Brij 35) for peptide mapping is described. The
      method was demonstrated by the separation of tryptic digestion of bovine serum
      albumin (BSA). The optimal mixed micelle solution was 50 mM NH(4)OH-HCOOH buffer
      (pH 2.0) containing 32 mM PAPS and 0.6% (m/v) Brij 35. It was found that the
      mixed micelle system permitted a highly selective separation of the tryptic
      digestion. The high separation selectivity was probably due to the ion-pairing
      interaction between the zwitterionic surfactant molecules and the peptides.

PMID- 16963323
TI  - Predicting 3D structures of transient protein-protein complexes by homology.
AB  - The paper reports a homology based approach for predicting the 3D structures of
      full length hetero protein complexes. We have created a database of templates
      that includes structures of hetero protein-protein complexes as well as domain
      domain structures (), which allowed us to expand the template pool up to 418 two
      chain entries (at 40% sequence identity). Two protocols were tested-a protocol
      based on position specific Blast search (Protocol-I) and a protocol based on
      structural similarity of monomers (Protocol-II). All possible combinations of two
      monomers (350,284 pairs) in the ProtCom database were subjected to both protocols
      to predict if they form complexes. The predictions were benchmarked against the
      ProtCom database resulting to false-true positives ratios of approximately 5:1
      and approximately 7:1 and recovery of 19% and 86%, respectively for protocols I
      and II. From 350,284 trials Protocol-I made only approximately 500 wrong
      predictions resulting to 0.5% error. In addition, though it was shown that
      artificially created domain-domain structures can in principle be good templates
      for modeling full length protein complexes, more sensitive methods are needed to
      detect homology relations. The quality of the models was assessed using two
      different criteria such as interfacial residues and overall RMSD. It was found
      that there is no correlation between these two measures. In many cases the
      interface residues were predicted correctly, but the overall RMSD was over 6 A
      and vice versa.

PMID- 16963324
TI  - Protection against glycation and similar post-translational modifications of
      proteins.
AB  - Glycation and other non-enzymic post-translational modifications of proteins have
      been implicated in the complications of diabetes and other conditions. In recent
      years there has been extensive progress in the search for ways to prevent the
      modifications and prevent the consequences of the modifications. These areas are
      covered in this review together with newer ideas on possibilities of reversing
      the chemical modifications.

PMID- 16963325
TI  - Influence of amino acid properties for discriminating outer membrane proteins at
      better accuracy.
AB  - Discriminating outer membrane proteins (OMPs) from other folding types of
      globular and membrane proteins is an important task both for identifying outer
      membrane proteins from genomic sequences and for the successful prediction of
      their secondary and tertiary structures. In this work, we have analyzed the
      influence of physico-chemical, energetic and conformational properties of amino
      acid residues for discriminating outer membrane proteins using different machine
      learning algorithms, such as, Bayes rules, Logistic functions, Neural networks,
      Support vector machines, Decision trees, etc. We observed that most of the
      properties have discriminated the OMPs with similar accuracy. The neural network
      method with the property, free energy change could discriminate the OMPs from
      other folding types of globular and membrane proteins at the 5-fold cross
      validation accuracy of 94.4% in a dataset of 1,088 proteins, which is better than
      that obtained with amino acid composition. The accuracy of discriminating
      globular proteins is 94.3% and that of transmembrane helical (TMH) proteins is
      91.8%. Further, the neural network method is tested with globular proteins
      belonging to 30 major folding types and it could successfully exclude 99.4% of
      the considered 1612 non-redundant proteins. These accuracy levels are comparable
      to or better than other methods in the literature. We suggest that this method
      could be effectively used to discriminate OMPs and for detecting OMPs in genomic
      sequences.

PMID- 16963326
TI  - Cortical auditory event-related potentials in newborn infants.
AB  - The possibility of recording changes in electroencephalography potentials
      following perception of sound was reported several decades ago. The recent
      expanding research on auditory cortical event-related potentials (AERPs) for
      assessing sound discrimination abilities in children and infants has indicated
      that several methodological issues need to be addressed before it can be
      implemented in clinical practice. Latencies, polarities, and amplitudes of the
      responses change with gestational age and during infancy. Thus, the maturation of
      the infant must be considered when designing stimulus paradigms and interpreting
      the responses. Of healthy newborn infants, only about 80% will show mismatch
      negativity, the automatic change detection of the auditory stimuli. Currently,
      the AERP method cannot be applied in clinical practice in the neonatal period,
      although the findings in healthy newborns at risk for dyslexia are promising.
      Further research will elucidate the possibility of developing AERPs as a possible
      early screening method during infancy for later dyslexia or cognitive
      dysfunction.

PMID- 16963327
TI  - Misconceptions V--Activation of osteoclasts is the first step in the bone
      remodeling cycle.

PMID- 16963329
TI  - Dietitians play important role in emergency preparedness.

PMID- 16963331
TI  - Nutritional gatekeepers and the 72% solution.

PMID- 16963332
TI  - To cosign or not to cosign: what managers need to consider.

PMID- 16963333
TI  - Improving access to school-based nutrition services for children with special
      health care needs.

PMID- 16963334
TI  - Getting that first job: search and resume tips.

PMID- 16963335
TI  - Ethical issues in research with human subjects.

PMID- 16963336
TI  - Passing an effective obesity bill.

PMID- 16963337
TI  - Framing the farm bill.

PMID- 16963338
TI  - What is the evidence of a causal relationship between dieting, obesity, and
      eating disorders in youth?

PMID- 16963340
TI  - The new normal: what girls say about healthy living--a report from the girl scout
      research institute.

PMID- 16963341
TI  - The high cost of not consuming fruits and vegetables.

PMID- 16963342
TI  - Most Americans eat much less than recommended amounts of fruits and vegetables.
AB  - OBJECTIVE: To estimate the proportions of the population meeting recommendations
      for fruit and vegetable intake, we first estimated the usual intake distributions
      of total fruits and vegetables and then compared the results to the 5 A Day
      recommendation and to the recommendations for fruits and vegetables combined,
      found in the new US Department of Agriculture food guide, MyPyramid.
      DESIGN/SUBJECTS: The primary dataset was created from one 24-hour recall from
      each of 8,070 respondents in the 1999-2000 National Health and Nutrition
      Examination Survey. Variances were estimated using one or two 24-hour recalls
      from 14,963 respondents in the 1994-1996 Continuing Survey of Food Intakes by
      Individuals. STATISTICAL ANALYSIS: The statistical method developed at Iowa State
      University was used for estimating distributions of usual intake of dietary
      components that are consumed daily. It was modified to allow the adjustment of
      heterogeneous within-person variances using an external estimate of
      heterogeneity. RESULTS: In 1999-2000, only 40% of Americans ate an average of
      five or more (1/2)-cup servings of fruits and vegetables per day. The proportions
      of sex-age groups meeting the new US Department of Agriculture recommendations
      ranged from 0.7% of boys aged 14 to 18 years, whose combined recommendation is 5
      cups, to 48% of children aged 2 to 3 years, whose combined recommendation is 2
      cups. CONCLUSIONS: Americans need to consume more fruits and vegetables,
      especially dark green and orange vegetables and legumes. Nutritionists must help
      consumers realize that, for everyone older than age 3 years, the new
      recommendations for fruit and vegetable intakes are greater than the familiar
      five servings a day.

PMID- 16963343
TI  - Consumption of whole-grain cereals during weight loss: effects on dietary
      quality, dietary fiber, magnesium, vitamin B-6, and obesity.
AB  - OBJECTIVE: While various weight-management approaches produce weight loss, they
      may differ in dietary quality. We monitored changes in nutrient intakes in
      overweight and obese subjects on three different weight-management programs.
      DESIGN: Randomized clinical trial (pilot study) with two 12-week phases: phase 1,
      weekly counseling; phase 2, monitoring only. SUBJECTS/SETTING: One hundred eighty
      nonsmoking, sedentary overweight and obese adults began this outpatient study;
      134 (body mass index [calculated as kg/m(2)]=30.9+/-2.4; age=42.3+/-1.2 years)
      were used in analyses. INTERVENTION: Twenty-four weeks of exercise only (control
      group), hypocaloric diet plus exercise, or hypocaloric diet with fiber-rich whole
      grain cereals plus exercise. MAIN OUTCOME MEASURES: At weeks 0, 12, and 24, diet
      quality was assessed by 3-day food records and body weight was measured.
      STATISTICAL ANALYSES PERFORMED: Three-way analysis of variance with repeated
      measures. RESULTS: The hypocaloric diet with fiber-rich whole-grain cereals plus
      exercise decreased energy intake more than exercise only (P=0.032). By week 12,
      the hypocaloric diet with fiber-rich whole-grain cereals plus exercise and the
      hypocaloric diet plus exercise decreased total fat more than exercise only, which
      was sustained in the hypocaloric diet with fiber-rich whole-grain cereals plus
      exercise at 24 weeks (P<0.001). At weeks 12 and 24, the hypocaloric diet with
      fiber-rich whole-grain cereals plus exercise reduced saturated fat intake more
      than exercise only. The hypocaloric diet with fiber-rich whole-grain cereals plus
      exercise increased total fiber, insoluble fiber (both P<0.001), magnesium
      (P=0.004), and vitamin B-6 (P=0.002) intakes more than the hypocaloric diet plus
      exercise and exercise only. Calcium and vitamin E intakes were inadequate in all
      groups. Weight loss was similar in the hypocaloric diet with fiber-rich whole
      grain cereals plus exercise and the hypocaloric diet plus exercise. CONCLUSIONS:
      Weight-reduction strategies may be associated with reduced intake of
      micronutrients, such as calcium and vitamin E. However, a hypocaloric diet with
      fiber-rich whole-grain cereal is effective for improving or maintaining other
      aspects of dietary quality during weight loss.

PMID- 16963344
TI  - Salad and raw vegetable consumption and nutritional status in the adult US
      population: results from the Third National Health and Nutrition Examination
      Survey.
AB  - OBJECTIVE: To examine the relationship between reported salad consumption and
      serum nutrient levels as well as dietary adequacy, as defined by nutrient
      intakes, in relation to the National Academy of Science Food and Nutrition Board
      Guidelines, in pre- and postmenopausal women and in men of comparable ages.
      DESIGN: Analyses of 24-hour recalls were conducted to determine dietary intake
      using the Third National Health and Nutrition Examination Survey data. Salad
      consumption was assessed based on intakes of salad, raw vegetables, and salad
      dressing. SUBJECTS: Nine thousand four hundred-six women and 8,282 men aged 18 to
      45 years and older than 55 years were examined between 1988 and 1994. STATISTICAL
      ANALYSES: Regressions were used to model associations between salad and raw
      vegetable consumption and selected serum nutrient outcomes. Usual nutrient intake
      distributions were estimated using the Iowa State University method for
      adjustment of the distribution. The Estimated Average Requirement method was used
      to determine the proportion of subjects with inadequate intake for each nutrient.
      RESULTS: The consumption of salads, raw vegetables, and salad dressing was
      positively associated with above-median serum micronutrient levels of folic acid,
      vitamins C and E, lycopene, and alpha- and beta-carotene. Each serving of salad
      consumed was associated with a 165% higher likelihood to meet the recommended
      Dietary Allowance for vitamin C in women and 119% greater likelihood in men.
      CONCLUSIONS: Salad consumers tended to have more favorable intakes of vitamins C
      and E, folic acid, and carotenoids, after adjustment for other differences. The
      significant and consistently higher serum values of these vitamins among salad
      consumers suggest that they are being well absorbed from salad. Salad, salad
      dressing, and raw vegetable consumption can be an effective strategy for
      enhancing nutritional adequacy and increasing vegetable consumption in the
      population at large.

PMID- 16963345
TI  - Motivating 18- to 24-year-olds to increase their fruit and vegetable consumption.
AB  - OBJECTIVE: This study assessed the effectiveness of a 4-month intervention using
      stage-based newsletters, computer-based communication, and motivational
      interviewing to increase fruit and vegetable consumption by college students aged
      18 to 24 years. DESIGN: Participants were stratified by stage of change for fruit
      and vegetable consumption and randomized to an intervention or control group.
      Participants completed the staging algorithm for fruit and vegetable intake,
      which included a one-item food frequency question, a 26-item food frequency
      questionnaire (FFQ), an 18-item decisional balance questionnaire, and a five-item
      self-efficacy questionnaire at baseline and completion of study. SUBJECTS: A
      convenience sample of 437 college students enrolled in a rural, land grant
      university was enrolled in the study. Only nondietetics majors between ages 18 to
      24 years were included in the study. A total of 314 students finished the study
      for a completion rate of 72%. INTERVENTION: After baseline staging and
      randomization, the intervention group participants received four stage-based
      newsletters, one motivational interview, and an individually tailored e-mail
      follow-up over a 4-month period. Control group participants only received
      assessment at baseline and at completion. MAIN OUTCOME MEASURES: Two fruit and
      vegetable instruments, a one-item food frequency question, and a 26-item FFQ
      measured daily consumption of fruits and vegetables at baseline and
      postintervention. STATISTICAL ANALYSES PERFORMED: The SAS system for Windows,
      version 8 (1999, SAS Institute, Inc, Cary, NC), was used for analysis, including
      the following tests: PROC GLM, PROC FREQ, and PROC NPAR1WAY, Kruskal-Wallis,
      Fisher, Wilcoxon rank sum, and chi(2). RESULTS: Fruit and vegetable consumption
      increased significantly more for the intervention group than the control group.
      Consumption increased in the intervention group by one serving a day for both
      instruments compared with 0.4 servings a day in the control group for a one-item
      instrument and no change in the control group for a 26-item FFQ. CONCLUSIONS:
      This intervention is an effective way to increase fruit and vegetable consumption
      by young adults.

PMID- 16963346
TI  - Portion distortion: typical portion sizes selected by young adults.
AB  - OBJECTIVE: The incidence of obesity has increased in parallel with increasing
      portion sizes of individually packaged and ready-to-eat prepared foods as well as
      foods served at restaurants. Portion distortion (perceiving large portion sizes
      as appropriate amounts to eat at a single eating occasion) may contribute to
      increasing energy intakes and expanding waistlines. The purpose of this study was
      to determine typical portion sizes that young adults select, how typical portion
      sizes compare with reference portion sizes (based in this study on the Nutrition
      Labeling and Education Act's quantities of food customarily eaten per eating
      occasion), and whether the size of typical portions has changed over time.
      SUBJECTS: Young adults (n=177, 75% female, age range 16 to 26 years) at a major
      northeastern university. METHODS: Participants served themselves typical portion
      sizes of eight foods at breakfast (n=63) or six foods at lunch or dinner (n=62,
      n=52, respectively). Typical portion-size selections were unobtrusively weighed.
      A unit score was calculated by awarding 1 point for each food with a typical
      portion size that was within 25% larger or smaller than the reference portion;
      larger or smaller portions were given 0 points. Thus, each participant's unit
      score could range from 0 to 8 at breakfast or 0 to 6 at lunch and dinner.
      Analysis of variance or t tests were used to determine whether typical and
      reference portion sizes differed, and whether typical portion sizes changed over
      time. RESULTS: Mean unit scores (+/-standard deviation) were 3.63+/-1.27 and
      1.89+/-1.14, for breakfast and lunch/dinner, respectively, indicating little
      agreement between typical and reference portion sizes. Typical portions sizes in
      this study tended to be significantly different from those selected by young
      adults in a similar study conducted 2 decades ago. CONCLUSIONS: Portion
      distortion seems to affect the portion sizes selected by young adults for some
      foods. This phenomenon has the potential to hinder weight loss, weight
      maintenance, and/or health improvement efforts. Thus, to ensure more effective
      nutrition counseling, food and nutrition professionals must develop ways to
      "undistort" what clients perceive to be typical portion sizes and help them
      recognize what is an appropriate amount to eat at a single eating occasion.

PMID- 16963347
TI  - Fat-related dietary behaviors of adult Puerto Ricans, with and without diabetes,
      in New York City.
AB  - OBJECTIVE: To assess the fat-related dietary behaviors of adult Puerto Ricans
      with and without diagnosed diabetes, living in New York City. DESIGN: A random
      digit-dialing telephone survey was conducted following Behavioral Risk Factor
      Surveillance System procedures. Dietary behavior was assessed using a brief Fat
      Related Diet Habits Questionnaire, in which higher scores indicated higher fat
      intake. SUBJECTS/SETTING: A total of 1,304 adult Puerto Ricans living in New York
      City were interviewed. Diabetes status was assessed using standard Behavioral
      Risk Factor Surveillance System questions. STATISTICAL ANALYSES PERFORMED:
      Weighted analyses using SUDAAN software for complex surveys were done, and t
      tests were used to assess differences in mean fat-related dietary score by
      sociodemographic and health characteristics. Age-adjusted least-squared means
      were used to compare scores between those with and without diabetes. Linear
      regression was used to model characteristics associated with fat-related dietary
      score. RESULTS: Fat-related dietary score was lower among those with diabetes and
      varied by population and health characteristics. Age-adjusted scores were
      significantly lower for those with diabetes who were younger, less educated,
      obese, or physically active. In the regression model, family history, weight, and
      exercise interacted with diabetes status. Those with diabetes were significantly
      more likely to modify meat consumption practices (eg, remove skin or trim fat) to
      reduce fat compared with those without diabetes. CONCLUSIONS: New York City
      Puerto Ricans with diabetes are somewhat more likely to engage in behaviors to
      reduce fat compared with those without diabetes. Targeted, culturally sensitive
      nutrition education and counseling emphasizing lower-fat food choices and other
      fat-reducing behaviors can help reduce risk and control diabetes. Education
      messages should be tailored to the individual's diabetes status and other health
      and sociodemographic characteristics.

PMID- 16963348
TI  - Impact of gestational diabetes mellitus nutrition practice guidelines implemented
      by registered dietitians on pregnancy outcomes.
AB  - Nutrition practice guidelines were developed for gestational diabetes mellitus by
      registered dietitians from the Diabetes Care and Education and the Women's Health
      and Reproductive Nutrition dietetic practice groups. To validate the guidelines,
      a clinical trial was designed with clinic sites randomly assigned to either
      nutrition practice guidelines care (12 sites) or usual nutrition care (13 sites),
      with diabetes, obstetric, and other clinic types represented in both groups.
      Volunteer dietitians served as study coordinators and recruited women diagnosed
      with gestational diabetes mellitus. The nutrition practice guidelines define
      medical nutrition therapy (MNT) for gestational diabetes and emphasize three
      areas-definition of MNT clinical goals with indexes to modify or advance MNT and
      criteria to start insulin; use of self-monitoring tools; and provision of three
      nutrition visits. Usual care sites provided prenatal nutrition care according to
      usual practice. The effect of nutrition care (sites following the nutrition care
      guidelines) and type of clinic site on changes in glycated hemoglobin and infant
      birth weight, adjusted for other covariates, were evaluated using linear
      regression. Differences in insulin use and other infant outcomes between
      treatment groups were evaluated using logistic regression. Generalized estimating
      equations were used to accommodate nonindependence within randomized clusters of
      patients within clinic sites. Data from 215 women indicated less insulin use at
      diabetes clinic sites in the nutrition practice guidelines groups and improved
      glycated hemoglobin control during the treatment period in diabetes clinics
      compared with obstetric or other clinics. A higher proportion of women in the
      usual care group had glycated hemoglobin levels that exceeded 6% at follow-up
      compared with women in the nutrition practice guidelines group (13.6% vs 8.1%),
      although not statistically significant (P=0.26). A significant clinic type and
      treatment group effect was found for birth weight. Nutrition practice guidelines
      for gestational diabetes mellitus reflected nutrition care already being provided
      by registered dietitians in diabetes clinics prior to this study because outcomes
      at these clinics were not impacted. Use of the guidelines by dietitians at
      obstetric and other clinics tended to improve outcomes at these sites.

PMID- 16963349
TI  - Telephone-based counseling improves dietary fat, fruit, and vegetable
      consumption: a best-evidence synthesis.
AB  - Eating more fruits/vegetables and less dietary fat rank among the most important
      nutrition recommendations for health improvement. Telephone counseling is an
      increasingly popular means of delivering support for diet modification. Using a
      best-evidence synthesis, the purpose of this review was to assess the
      effectiveness of telephone-based counseling on improving dietary fat, fruit, and
      vegetable consumption for adults. Online databases and article bibliographies
      were searched to produce relevant randomized-controlled trials published during
      the past 5 years. Nine studies were ultimately included and the weight of the
      evidence indicated that telephone-based counseling promotes significantly greater
      improvements in fruit/vegetable consumption (median effect size=0.41) and dietary
      fat intake (median effect size=0.22) relative to usual care. Improvements were
      especially pronounced among women with (or at high risk for developing) cancer.
      In some studies, telephone-based counseling was also associated with greater
      improvement in blood lipid levels and weight. Based on these findings, several
      design considerations (eg, population focus, counseling intensity) for program
      managers are proposed. Telephone-based counseling was found to be a moderately
      effective intervention, but there are not enough studies yet to draw conclusions
      on other research questions, such as how advantageous telephone-based counseling
      is over traditional forms of dietary counseling. At present, telephone-based
      counseling may best be used as a complement to clinical care and a means to
      broaden the outreach of nutrition services.

PMID- 16963350
TI  - Whole-grain diets reduce blood pressure in mildly hypercholesterolemic men and
      women.
AB  - The objective of this study was to compare the effects on blood pressure of
      predominantly insoluble fiber (whole wheat and brown rice) and soluble fiber
      (barley) in a whole-grain diet. Subjects (seven men, nine premenopausal women,
      and nine postmenopausal women) consumed a controlled Step I diet for 2 weeks;
      then about 20% of energy was replaced with whole wheat/brown rice, barley, or
      half wheat-rice/half barley, for 5 weeks each. Blood pressure was determined
      weekly and weight daily before breakfast. Urinary excretions of minerals that
      might affect blood pressure and urea nitrogen were determined each period.
      Systolic pressure was lower after the wheat/rice and half-and-half diets.
      Diastolic and mean arterial pressures were reduced by all whole-grain diets. No
      differences were observed in urinary measurements. In a healthful diet,
      increasing whole-grain foods, whether high in soluble or insoluble fiber, can
      reduce blood pressure and may help to control weight.

PMID- 16963351
TI  - The relationship between self-rated health status and the overall quality of
      dietary intake of US adolescents.
AB  - The objective of this study was to compare the quality of overall dietary intake
      of US adolescents by self-rated health status. Using 2 nonconsecutive days of
      dietary recall data and responses to a single question describing self-rated
      health status from the Continuing Survey of Food Intakes by Individuals 1994
      1996, linear regression analysis was used to detect differences in Healthy Eating
      Index (HEI) scores by self-rated health status for 1,504 adolescents, ages 11 to
      18 years. After adjusting for factors related to both overall dietary quality and
      self-rated health status, overall HEI scores did not differ by self-reported
      health status. However, two individual HEI component scores were found to be
      significantly related to adolescent self-rated health status: the vegetables
      score (P=0.01) was higher among those with positive self-rated health status, and
      the total fat score (P=0.01) was higher among those with negative self-rated
      health status. Self-perception of health status is not related to the overall
      quality of the adolescent diet; therefore, food and nutrition professionals
      should focus on understanding motivators other than health status when exploring
      adolescent dietary behaviors.

PMID- 16963352
TI  - Should we discuss weight and calories in adolescent obesity prevention and weight
      management programs? Perspectives of adolescent girls.
AB  - The purpose of this pilot study was to explore adolescent girls' perspectives on
      potentially sensitive topics related to weight management. Data were collected
      using individual semistructured interviews. Thirty high school-aged girls, who
      were at risk for overweight and had participated in a school-based obesity
      prevention program, were interviewed. Data were analyzed using qualitative
      methodology. Girls were mixed on whether nutrition-related information and
      messages should emphasize weight control or health. Although girls expressed
      interest in weight-related issues, some had concerns that overemphasizing weight
      control might lead to unhealthful and excessive weight preoccupation. Whereas
      many girls want to receive information on weight and calories to guide their
      decision making about food choices, care must be taken to avoid unintended
      harmful consequences.

PMID- 16963353
TI  - Sources and severity of self-reported food intolerance after ileal pouch-anal
      anastomosis.
AB  - Data on food intolerance after ileal pouch-anal anastomosis are scarce. The aim
      of this study was to identify foods causing intolerance and to determine the
      nature and severity of reported symptoms. Patients from the Dutch Crohn's and
      Ulcerative Colitis Association were mailed a survey on food intolerance; 105 (31%
      men) of 137 patients took part. They all reported intolerance to one or more
      foods. Common symptoms (scored from 0=absent to 10=severe), included diarrhea
      (mean score=5.8), fatigue (mean score=5.5), and thirst (mean score=4.6). Spicy
      foods, cabbage, and citrus fruits (or juice) were most likely to decrease stool
      consistency, increase stool frequency, or cause perianal irritation. Onions,
      cabbage, or leeks were reported by 28% of the patients to cause flatulence. The
      urge to defecate was stronger after a cooked meal (45% within (1/2) hour) than
      after sandwiches (15% within (1/2) hour). Foods reported to increase stool
      consistency were potato products, bread, and bananas. This study demonstrates
      that food intolerance is a common, albeit mild, problem after ileal pouch-anal
      anastomosis. Food and nutrition professionals should encourage patients to base
      their food choices on individual tolerance as long as no (patho-) physiological
      based evidence to the contrary is available.

PMID- 16963354
TI  - Internet food marketing strategies aimed at children and adolescents: a content
      analysis of food and beverage brand web sites.
AB  - Americans are spending an increasing amount of time using "new media" like the
      Internet. There has been little research examining food and beverage Web sites'
      content and marketing practices, especially those that attract children and
      adolescents. The purpose of this study was to conduct a content analysis of food-
      and beverage-brand Web sites and the marketing techniques and advertising
      strategies present on these sites. The top five brands in eight food and beverage
      categories, 40 brands in total, were selected based on annual sales data from
      Brandweek magazine's annual "Superbrands" report. Data were collected using a
      standardized coding form. The results show a wide variety of Internet marketing
      techniques and advertising strategies targeting children and adolescents.
      "Advergaming" (games in which the advertised product is part of the game) was
      present on 63% of the Web sites. Half or more of the Web sites used cartoon
      characters (50%) or spokescharacters (55%), or had a specially designated
      children's area (58%) with a direct link from the homepage. With interactive
      media still in its developmental stage, there is a need to develop safeguards for
      children. Food and nutrition professionals need to advocate for responsible
      marketing techniques that will support the health of children.

PMID- 16963355
TI  - How many grams of trans-fat are recommended per day?

PMID- 16963356
TI  - Comparative analysis of the human angiotensin II type 1a receptor heterologously
      produced in insect cells and mammalian cells.
AB  - Angiotensin II type 1a receptor (AT1aR) is a member of GPCR superfamily and it
      plays crucial roles in the regulation of blood pressure, hormone secretion and
      renal functions. Here, we report functional overexpression and characterization
      of the human AT1aR in insect cells using the baculovirus system and in mammalian
      cells using the Semliki Forest virus system. The recombinant receptor was
      expressed at a level of 29-32 pmol/mg and it binds to angiontensin II with high
      affinity (Kd=0.98-1.1 nM). Angiotensin II stimulated accumulation of inositol
      phosphate and phosphorylation of MAP kinase was also observed, which indicated
      that the recombinant AT1aR could couple to endogenous Galphaq protein. Confocal
      laser scanning microscopy revealed that the recombinant receptor was
      predominantly localized in the plasma membrane and agonist induced
      internalization of the recombinant AT1aR was also observed. The recombinant AT1aR
      was expressed in glycosylated form and in vivo inhibition of glycosylation
      suppressed its surface expression.

PMID- 16963357
TI  - A novel ex vivo culture system for studying bone repair.
AB  - Repair of large bony defects still remains a challenge for surgeons.
      Hydroxyapatite (HA) is well known for its biocompatibility and osseoconduction
      properties in the osseous environment. In this study the biofunctionality of a
      newly developed scaffold comprising of collagen and HA, with variable macropores
      was examined. The biological response was evaluated using primary human
      osteoblast cells (HOBs). Cell infiltration, proliferation and differentiation
      were assessed. The results showed that HOBs were able to migrate from the
      collagen into the HA pores with greater cell migration and infiltration observed
      in those scaffolds with larger pores. Furthermore, it was shown that Alkaline
      Phosphatase, a differentiation marker for HOBs was enhanced as the average
      macropore size increased. This in vitro model provides a more relevant method of
      testing the biofunctionality and migration ability of cells at a trauma site
      following implantation in bone and cartilage.

PMID- 16963358
TI  - Accelerated bone healing and excessive callus formation in patients with femoral
      fracture and head injury.
AB  - The effect of head injury on systemic physiology, including bone healing is still
      a topic of vivid discussion. Whether the observed changes genuinely represent
      accelerated fracture healing or are a form of local heterotopic ossification
      remains unclear. We aimed to investigate whether in patients with long bone
      fractures the presence of head injury is associated with accelerated bone healing
      and excessive callus formation. In total 67 patients were studied 17 with head
      injury and 50 without head injury (25 treated with reamed and the other 25 with
      the unreamed nailing technique). Both groups were comparable in terms of age,
      sex, ISS. All underwent stabilisation of their femoral fracture with
      intramedullary nailing. The quantification of fracture healing response was
      estimated by taking the radiological ratio of the largest diameter of callus
      formed into two planes and the adjacent normal diameter of femoral canal. The
      minimum follow up of the patients was 12 months. In patients with head injury,
      the mean time to fracture union was significantly shorter than either the reamed
      or unreamed group (10.5 weeks compared with 20.5 and 26.9 weeks, p<0.001). The
      difference between the mean callus to diaphyseal ratio was statistically
      significant for both the AP and Lateral projections (AP: mean difference 0.462,
      95% CI 0.312 to 0.602, p<0.0001, LAT: mean difference 0.289, 95% CI 0.142 to
      0.436, p<0.001) with the head injured patients having more florid callus compared
      to the control group.

PMID- 16963359
TI  - Enhancing the osteoinductive properties of hydroxyapatite by the addition of
      human mesenchymal stem cells, and recombinant human osteogenic protein-1 (BMP-7)
      in vitro.
AB  - Hydroxyapatite (HA) has been widely used as a bone graft substitute. In this
      study, we investigated whether the addition of osteogenic protein-1 (OP-1)
      further enhanced the weak osteoinductive properties of hydroxyapatite when loaded
      with human mesenchymal stem cells (h-MSCs). Over a 14 day period, cell
      proliferation in both groups was assessed qualitatively using SEM and
      quantitatively using alamar blue assay. Cell differentiation was also evaluated
      by measurement of ALP activity, which was expressed against total DNA. HA/MSC
      loaded with OP-1 demonstrated a statistically significant increase (p<0.001) in
      cell proliferation at all time points in comparison to unloaded samples. ALP
      activity per DNA was also significantly enhanced (p<0.001) in loaded samples when
      compared to unloaded controls. SEM demonstrated increased cellular attachment and
      proliferation into HA pores at all time points in the loaded samples. Our study
      suggests that the osteoinductive potential of HA can be improved in vitro by the
      combined incorporation of MSCs and OP-1.

PMID- 16963360
TI  - An ongoing research for evaluation of treatment with BMPs or AGFs in long bone
      non-union: protocol description and preliminary results.
AB  - Treatment of long bone non-union (NU) continues to be a challenging task for the
      trauma surgeon often resulting in unsatisfactory results and long-term morbidity.
      Whilst autologous bone grafting remains the gold standard of treatment of these
      difficult cases, recently, due to the advances made in tissue engineering
      techniques, other alternatives have become available. In this study we report our
      preliminary results of treating long bone non-unions using either bone
      morphogenetic protein-7 (BMP-7) or platelet rich plasma (PRP) concentrations.
      Twenty-nine cases have entered this study thus far. Preliminary results indicate
      that BMP-7 is more efficacious that PRP as there was a significant failure rate
      of 6.2% versus 38.5% between BMP-7 and PRP, respectively.

PMID- 16963361
TI  - Changes in patients' illness representations before and after elective
      percutaneous transluminal coronary angioplasty.
AB  - BACKGROUND: Elective percutaneous transluminal coronary angioplasty (PTCA) is an
      increasingly popular treatment for coronary heart disease, but little is known
      about individuals' cognitive responses to this intervention. As part of adapting
      to living with chronic disease, individuals develop unique models, or illness
      representations, which enable them to "make sense" of their predicament.
      Inaccurate illness representations have a negative affect on patient behaviors
      and outcomes. OBJECTIVE: This purpose of this study was to examine changes in
      patients' self-reported illness representations before and after first-time
      elective PTCA. METHODS: In this descriptive, repeated-measures design, illness
      representations were evaluated in 117 consecutive patients attending a pre-PTCA
      clinic using the Illness Perceptions Questionnaire. Data were collected pre- and
      6 to 8 months post-elective PTCA. RESULTS: A typical participant was male (75%),
      of European ethnicity (90%), and aged 62 years (+/-10.7). Six to 8 months post
      PTCA self-reported symptom frequency (Z = 8.034, N-ties, P = .000) and duration
      decreased significantly (Z = 8.361, N-ties 20, P = .000) compared with pre-PTCA
      levels. Timeline scores increased significantly (Z = 3.46, N-ties 10, P = .001)
      indicating a shift in patients' representations of their disease from an acute to
      a chronic model. Cure/control and consequence scores decreased significantly,
      indicating that representations regarding personal control over their illness
      weakened (Z = 3.251, N-ties 18, P = .001), as did their representation of their
      illness as having serious consequences (Z = 5.250, N-ties 0, P = .00).
      CONCLUSION: Some inaccuracies in illness representations were evident, some of
      which evolved to more realistic representations, whereas others did not. In the
      era of promoting effective self-management among those living with chronic
      diseases a clear understanding of illness representation in the context of
      coronary heart disease is valuable, particularly as inaccuracies are associated
      with negative outcomes.

PMID- 16963362
TI  - Psychosocial morbidity among parents of children with congenital heart disease: a
      prospective longitudinal study.
AB  - OBJECTIVE: The study objectives were to assess long-term psychosocial morbidity
      and its determinants among parents of children with congenital heart disease
      (PCCHD), and to compare mothers with fathers on psychosocial variables. METHOD:
      The study design was longitudinal. Data comprising PCCHD (n = 632, 58% were
      women) were collected on two occasions 1 year apart. RESULTS: Many PCCHD reported
      psychosocial problems manifested in depression (18%), anxiety (16%-18%),
      somatization (31%-38%), and hopelessness (16%) during both measurement points. In
      addition, 7% to 22% reported psychosocial problems persisting over a 1-year
      period. Consistently over time, mothers reported more severe symptoms of
      depression, anxiety, somatization, and hopelessness than fathers. Children's
      clinical severity did not significantly explain parent's psychosocial morbidity
      over time. Instead, parental caregiving burden, dissatisfaction with care, social
      isolation, and financial instability were associated with an increased risk of
      long-standing psychosocial morbidity. CONCLUSIONS: An important proportion of
      PCCHD are at risk of long-standing psychosocial morbidity, suggesting that
      psychosocial intervention may be beneficial. Feasible interventions are
      discussed.

PMID- 16963363
TI  - The synergistic effect of heart disease and diabetes on self-management,
      symptoms, and health status.
AB  - BACKGROUND: Coronary heart disease (CHD) and diabetes may have synergistic
      effects on symptoms, self-management, and general and cardiac-specific health
      status. PURPOSE: We compared symptom distress, self-management difficulties, and
      general and cardiac-specific health status in patients with CHD by the presence
      and severity of diabetes. METHODS: We performed a cross-sectional study of 1013
      patients enrolled in the COURAGE trial, with the use of clinical data, the
      Symptom Distress Scale, the Self-Management Difficulties Scale, the Short-Form
      36, and the Seattle Angina Questionnaire. RESULTS: Patients with diabetes and
      greater severity of diabetes had worse findings in symptom distress, self
      management difficulties, and general and cardiac-specific health status than
      patients without diabetes. CONCLUSIONS: A robust effect of diabetes on symptom
      distress and self-management difficulties was found in patients with CHD. The
      results from the Seattle Angina Questionnaire illustrate difficulty in
      attributing physical limitations to specific symptoms or conditions, and show the
      experience of comorbid conditions to be synergistic. Clinicians' understanding of
      this synergy and integration of condition-specific care with general treatment
      and self-management practices are needed.

PMID- 16963364
TI  - Correlates of functional limitations in older Chinese patients with chronic
      obstructive pulmonary disease in Hong Kong.
AB  - BACKGROUND: Few studies have examined functional limitations in Chinese elders
      with chronic obstructive pulmonary disease (COPD). OBJECTIVES: The objective was
      to describe the functional limitations, respiratory status, and psychologic
      status of Chinese elders with COPD; to examine the relationships between
      functional limitations and selected variables including age, gender, duration of
      COPD, and hospital readmission history; and to identify the variables that
      predict functional limitations in Chinese elders with COPD. METHOD: A
      correlational predictive study was performed with a sample of 97 Chinese elders
      with COPD. The subjects were 65 years or older and recruited from two hospitals
      in Hong Kong. Data were individually collected on the day the individual was to
      be discharged from the hospital, by using the Barthel Index for functional
      limitations, forced expiratory volume in 1 second percent predicted for
      respiratory status, and General Health Questionnaire (28 items) for psychologic
      status. Information on age, gender, duration of COPD, and hospital readmission
      history were also identified from the medical record. RESULTS: Functional
      limitations in Chinese elders with COPD were significantly correlated with poorer
      respiratory status and more depressive symptoms. Multiple regression analysis
      indicated that depressive symptoms were a significant predictor of functional
      limitations after controlling for the effect of respiratory status. DISCUSSION:
      The results of this study demonstrate that depressive symptoms to some extent
      predict functional limitations in Chinese elders with COPD. Investigation of the
      effect of appropriate screening and interventions for depressive symptoms on
      preventing, delaying, or reducing functional limitations in this patient group is
      suggested.

PMID- 16963365
TI  - Comparison of the effectiveness of manual and ventilator hyperinflation at
      different levels of positive end-expiratory pressure in artificially ventilated
      and intubated intensive care patients.
AB  - BACKGROUND: Manual hyperinflation (MHI) and ventilator hyperinflation (VHI) are
      two methods of recruitment maneuvers used in ventilated patients to improve lung
      compliance and secretion mobilization. The use of VHI may minimize the adverse
      effects of disconnection from the ventilator, but it is uncertain whether high
      levels of positive end-expiratory pressure (PEEP) would decrease the peak
      expiratory flow rate (PEFR) and consequently affect secretion clearance.
      OBJECTIVES: The aim of this study was to compare the effectiveness of MHI and VHI
      in terms of clearing pulmonary secretions (sputum wet weight and PEFR), improving
      static respiratory system compliance and oxygenation (arterial oxygen
      tension/fraction of inspired oxygen), and altering mean arterial pressure, heart
      rate, and carbon dioxide output at different levels of PEEP. METHODS: This was a
      randomized crossover study involving 14 general intensive care patients who were
      intubated and mechanically ventilated. RESULTS: Sputum production was similar in
      both techniques and levels of PEEP. There were no differences in improvement in
      oxygenation and static respiratory system compliance between MHI and VHI.
      However, VHI increased Cst significantly at 30 minutes posttreatment (P = .012),
      and a significant difference was observed between levels 5 and 7.5 cmH(2)O (P =
      .02) of PEEP for MHI. MHI generated higher PEFR than VHI (P < .05). No adverse
      change in heart rate or mean arterial pressure was observed during either
      technique; however, VCO(2) was significantly different for techniques (P = .045)
      and over time (P = .05). CONCLUSION: The VHI technique seems to promote greater
      improvements in respiratory mechanics with less metabolic disturbance compared
      with MHI. Other variables such as sputum production, hemodynamics, and
      oxygenation were affected similarly by both techniques.

PMID- 16963366
TI  - Predictors of emergency department visit disposition for patients with chronic
      obstructive pulmonary disease.
AB  - STUDY OBJECTIVES: The study objective was to validate among patients with chronic
      obstructive pulmonary disease (COPD) clinical predictors of emergency department
      (ED) disposition (admission vs discharge) found in a previous study. We
      hypothesized that the initial heart rate (HR) at presentation and the number of
      nebulizer treatments would predict visit disposition adequately and that existing
      triage criteria would not. METHODS: In this correlational study, all ED visits to
      a university medical center related to a diagnosis of COPD over a 2-year period
      were identified and reviewed retrospectively (N = 114 patients and 226 visits).
      Associations of clinical predictors with visit disposition was by contingency
      table or receiver operating characteristic curve analysis. RESULTS: The overall
      admission rate was 60.2%. An initial HR slightly greater than normal limits (HR
      >/= 106 vs HR </= 105 beats/min) predicted visit disposition; receiver operating
      characteristic area under curve (95% confidence interval) = .67 (.60-.73);
      sensitivity = .61 (.52-.69); and specificity = .68 (.57-.77). Likelihood ratios
      for positive and negative tests were 1.93 and 0.57, corresponding to posterior
      probabilities of admission = .74 and .46, respectively. Triage classification did
      not adequately predict visit disposition. Patients receiving three or more
      nebulized bronchodilator treatments were more likely to be admitted than those
      receiving fewer treatments, but this predictor had low sensitivity and was no
      more discriminating than the initial HR. Women were more likely than men to be
      admitted, odds ratio = 2.66 (1.54-4.61), but there were few clinically meaningful
      differences between sexes. CONCLUSIONS: The initial HR on arrival predicted
      disposition of ED visits for patients with COPD with operating characteristics
      that were superior to the existing triage criteria. Triage of patients with COPD
      could be improved simply, and at no additional expense, by recognizing that
      almost any degree of tachycardia in a patient with COPD substantially increases
      the likelihood of admission.

PMID- 16963367
TI  - Obstructive metastatic malignant melanoma of the heart: Imminent pulmonary
      arterial occlusion caused by right ventricular metastasis with unknown origin of
      the primary tumor.
AB  - Whether primary or metastatic, cardiac neoplastic diseases are relatively
      uncommon disorders. Although any malignancy may involve the heart, malignant
      melanoma (MM) has a significant tendency to metastasize to the heart. Cardiac
      involvement may occur during the course of MM or years after surgical therapy,
      but rarely metastasis may be the initial manifestation of the disease. This
      article reports a metastatic MM case that was initially manifested by heart
      failure symptoms because of right ventricle outflow obstruction and for which the
      primary focus could not be determined.

PMID- 16963368
TI  - Cardiac tamponade complicating trimodal therapy for malignant mesothelioma.
AB  - Trimodal therapy, which includes extrapleural pneumonectomy as the cytoreductive
      procedure followed by combination chemoradiotherapy, is becoming the standard of
      care in the treatment of malignant mesothelioma. We report here a case of
      hypotension secondary to tension hydrothorax in which echocardiography and
      hemodynamic monitoring demonstrated evidence of tamponade physiology.
      Thoracentesis was lifesaving.

PMID- 16963369
TI  - Fever of unknown origin (FUO) caused by multiple myeloma: the diagnostic value of
      the Naprosyn test.
AB  - Fever of unknown origin (FUO) remains a difficult diagnostic problem. The causes
      of FUO have changed over the years. Neoplastic disorders have now displaced
      infectious diseases as the most common cause of FUOs. Most neoplasms are
      associated with no or low-grade temperatures, with some important exceptions.
      Hypernephromas and lymphomas are neoplasms typically associated with high spiking
      fevers or may present as FUOs. Hematologic malignancies, that is, the acute and
      chronic leukemias, myeloproliferative disorders, and multiple myeloma, do not
      usually present with acute fevers or as FUOs. We present an elderly male patient
      who presented with an FUO, whose history is significant for multiple myeloma in
      remission. Differential diagnostic possibilities in this patient included plasma
      cell leukemia, relapse of multiple myeloma, secondary/superimposed malignancy, or
      opportunistic infection. The main differential diagnosis for his FUO was between
      neoplastic and infectious disorders. As part of the diagnostic workup, a Naprosyn
      test (naproxen 375 mg [by mouth] every 12 hours for 3 days) was used to
      differentiate neoplastic from infectious causes of FUO in this patient. The
      Naprosyn test was positive, which indicated a neoplastic explanation for the
      patient's FUO and eliminated, along with the infectious disease workup, an
      infectious explanation for his FUO. The patient's FUO was finally determined to
      be the result of a relapse of multiple myeloma and not of a secondary malignancy
      or malignant transformation of myeloma into plasma cell leukemia. We conclude the
      Naprosyn test remains a valuable diagnostic test to use to narrow differential
      diagnostic possibilities in patients with FUOs when a malignancy is a diagnostic
      consideration.

PMID- 16963373
TI  - Epidemiology of occupational low back pain.
AB  - There have been significant advances in our understanding of occupational low
      back pain over the last decade largely because of a noteworthy improvement in the
      number and quality of prospective trials. More recent work confirms that genetic
      factors may drive a large portion of thr risk factors. The importance of physical
      fitness and spine support muscle fitness is believed to protect against future
      occurrences. Psychosocial factors can play a role in increasing the risk of
      future low back pain and acute pain in becoming chronic. Some of the
      psychological influence may be through a muscular pain component. It is arguable
      that an emphasis should be placed on resources, education, and support to allow
      workers to be productive whether suffering from back pain or not.

PMID- 16963374
TI  - Prevention strategies for occupational low back pain.
AB  - The authors investigate the effects of worker education and training, exercise,
      and ergonomics on the incidence of low back pain in occupational settings.
      Prevention strategies that involve risk factor modification, worker selection,
      and lumbar orthotics are also examined.

PMID- 16963375
TI  - Occupational low back pain.
AB  - Low back injury is one of the most common conditions in the workplace. The causes
      are multifactorial and must be sought during the physician's examination. Failure
      to perform a comprehensive history and physical examination ultimately can lead
      to treatment failure and injury recurrence. A comprehensive history and physical
      may help clinicians to differentiate organic and nonorganic causes of low back
      pain. Different diagnoses need specific rather than generalized treatment
      programs. Teaching clinicians the nuances of the history and physical examination
      in a setting with an injured worker is the goal of this article.

PMID- 16963376
TI  - Diagnosis of low back pain: role of imaging studies.
AB  - Approximately 70% of North Americans experience low back pain during their
      lifetime, with most of them demonstrating improvement within 2 to 4 weeks. The
      use of early radiographic evaluation is often unnecessary for uncomplicated acute
      low back injuries. Select patient populations have been identified for early
      evaluation. If the following red flags are associated with the pain, spinal
      imaging is indicated: possible fracture, neoplasm, infection, and cauda equina
      syndrome. High suspicion for the presence of one of these entities should prompt
      more formal evaluation of the spine. This article provides an overview of the
      commonly used diagnostic procedures in the evaluation of lumbar spine disorders.

PMID- 16963377
TI  - The role of electrodiagnosis in the evaluation of low back pain.
AB  - Establishing a specific diagnosis is important in the effective management of
      individuals who present with a complaint of low back pain. Electrodiagnostic
      studies are an integral part of the diagnostic evaluation when the history or
      physical examination suggests that neural structures may contribute as symptom
      generators. Lumbo-sacral radiculopathies, plexopathies, and peripheral nerve
      injuries are of primary concern when evaluating individuals with low back pain,
      and electrodiagnostic studies assist in identifying and quantifying
      neurophysiologic injuries and abnormalities using techniques. A thorough,
      thoughtful, and individualized electrodiagnostic study performed by qualified
      physicians as an extension of a detailed history and physical examination can be
      an important and useful component in the proper evaluation of individuals with
      low back pain.

PMID- 16963378
TI  - The role of exercise in the prevention and management of acute low back pain.
AB  - The transition from acute pain to chronic pain and onward to disability is
      burdensome emotionally and financially to individual sufferers, loved ones,
      employers, and the health care system. Up to 40% of acute low back pain cases can
      become chronic and lead to disability in some cases. Treatments that reduce risk
      of chronic pain by successful management of acute low back pain are highly
      desirable. Prevention of acute low back pain is even more desirable. Exercise has
      been part of the armamentarium of treating and preventing acute low back pain,
      especially as a means of avoiding disability. This article critically reviews
      studies of the role of exercise in the management and prevention of low back
      pain.

PMID- 16963379
TI  - Spinal stabilization exercises for the injured worker.
AB  - Returning the injured worker to his previous occupation can be a difficult and
      complex rehabilitation process. The goal of standard stabilization exercises
      (SSE) is to facilitate the active system for improved dynamic spinal stability.
      Improving dynamic spinal stability can decrease the forces placed on the
      intervertebral joints, which minimizes the chance of reinjury. When used in
      conjunction with industrial rehabilitation, SSEs offer the optimal environment
      for an injured worker to practice his occupational demands while using
      appropriate spinal stabilization.

PMID- 16963380
TI  - Use of medications in the treatment of acute low back pain.
AB  - The prescription of medications continues to be one of the mainstays of treatment
      of acute low back pain episodes. The goals of the pharmacologic treatment for
      acute low back are reduction of pain and return of normal function. Often,
      nociception is a result of secondary inflammation and muscle spasm after acute
      injury of a structure of the spine, which may include muscle, tendon, ligament,
      disc, or bone. An understanding of the appropriate use of medications to address
      the underlying pain generator and the current evidence for using these
      medications is essential for any physician who sees and treats patients with
      acute low back pain.

PMID- 16963381
TI  - Lumbar spine injection and interventional procedures in the management of low
      back pain.
AB  - Lumbar spine injections play a role in the evaluation and treatment of low back
      pain and lumbar radiculopathy. These injection procedures have been demonstrated
      to be effective in determining the pain generator for low back pain. There is
      still debate as to the long-term pain relief from epidural and intra-articular
      facet joint injections, and no controlled studies have examined the long-term
      effects of SI joint injections. Additional investigation is certainly warranted
      to evaluate further the long-term benefits and determine with patients would
      benefit the most from these injections. Current evidence validates that these
      injections provide temporary relief of low back and radicular leg pain up to
      several months, if not longer. This duration of pain relief creates an
      opportunity to maximize rehabilitation efforts while symptoms are minimal.

PMID- 16963382
TI  - Surgical issues in the injured worker with lower back pain.
AB  - Although most workers who sustain lower back can be managed without surgery, a
      carefully selected subset of patients benefit from operative intervention. When
      evaluating these patients, care must be taken to identify surgical emergencies,
      including patients with cauda equina syndrome and progressive neurologic deficits
      and patients with cauda equina syndrome and progressive neurologic deficits and
      patients with certain historical red flags that should prompt further evaluation.
      Conditions that may benefit from surgery include lumbar disc herniations,
      discogenic back pain, spinal stenosis, and spondylolisthesis. This article
      reviews the indications for surgery in injured workers and expected postoperative
      outcomes.

PMID- 16963383
TI  - Impairment and disability rating in low back pain.
AB  - Many publications emphasize the theoretical relationship between impairment,
      disability, and the workplace. This article intended to provide the reader with
      some framework in this regard, but its main intent is to create a practical how
      to-guide in the evaluation of impairment and disability that result from low back
      pain.

PMID- 16963385
TI  - Estimates of pregnancies averted through California's family planning waiver
      program in 2002.
AB  - CONTEXT: During its first year of operation (1997-1998), California's family
      planning program, Family PACT, helped more than 750,000 clients to avert an
      estimated 108,000 pregnancies. Given subsequent increases in the numbers of
      clients served and contraceptive methods offered by the program, updated
      estimates of its impact on fertility are needed. METHODS: Claims data on
      contraceptives dispensed were used to estimate the number of pregnancies
      experienced by women in the program in 2002. Medical record data on methods used
      prior to enrollment were used to predict client fertility in the absence of the
      program. Further analyses examined the sensitivity of these estimates to
      alternative assumptions about contraceptive failure rates, contraceptive
      continuation and contraceptive use in the absence of program services. RESULTS:
      Almost 6.4 million woman-months of contraception, provided primarily by oral
      contraceptives (57%), barrier methods (19%) and the injectable (18%), were
      dispensed through Family PACT during 2002. As a result, an estimated 205,000
      pregnancies-which would have resulted in 79,000 abortions and 94,000 births,
      including 21,400 births to adolescents-were averted. Changing the base
      assumptions regarding contraceptive failure rates or method use had relatively
      small effects on the estimates, whereas assuming that clients would use no
      contraceptives in the absence of Family PACT nearly tripled the estimate of
      pregnancies averted. CONCLUSION: Because all contraceptive methods substantially
      reduce the risk of pregnancy, Family PACT's impact on preventing pregnancy lies
      primarily in providing contraceptives to women who would otherwise not use any
      method.

PMID- 16963386
TI  - Understanding sex partner selection from the perspective of inner-city black
      adolescents.
AB  - CONTEXT: Black adolescents in inner-city settings are at increased risk for HIV
      and other STDs. Sex partner characteristics, as well as individual behavior,
      influence individuals' STD risk, yet little is known about the process of sex
      partner selection for adolescents in this setting. METHODS: Semistructured in
      depth interviews were conducted during the summer and fall of 2002 with 50 inner
      city black adolescents (26 females and 24 males) who had been purposively
      recruited from an STD clinic. Content analysis was used to study interview texts.
      RESULTS: Young women desire a monogamous romantic partner, rather than a casual
      sex partner; however, to fulfill their desire for emotional intimacy, they often
      accept a relationship with a nonmonogamous partner. Young men seek both physical
      and emotional benefits from being in a relationship; having a partner helps them
      to feel wanted, and they gain social status among their peers when they have
      multiple partners. For men, these benefits may help compensate for an inability
      to obtain jobs that would improve their financial and, as a result, social
      status. Both women and men assess partners' STD risk on the basis of appearance.
      CONCLUSIONS: HIV and other STD prevention initiatives must go beyond the scope of
      traditional messages aimed at behavior change and address the need for social
      support and socioeconomic opportunities among at-risk, inner-city adolescents.

PMID- 16963387
TI  - Provision of contraceptive and related services by publicly funded family
      planning clinics, 2003.
AB  - CONTEXT: In addition to contraceptive services, publicly funded family planning
      clinics provide low-income women with a range of reproductive diagnostic,
      treatment and educational services. Nationally representative information about
      the scope of services available from clinics is needed to formulate policy and
      programmatic recommendations. METHODS: In 2003, more than 1,000 U.S. clinics
      responded to an eight-page survey on service availability and clinic policies.
      Differences in the proportions of clinics reporting each service or policy were
      examined by clinic type and receipt of Title X funding. RESULTS: Nearly all
      clinics offer pills, injectables and condoms; 75% offer the patch; and 80% offer
      emergency contraception. Most clinics (73%) typically use a conventional Pap
      smear for initial cervical cancer screenings; 27% use liquid-based Pap tests. For
      follow-up, 68% of clinics use liquid-based or other advanced testing. Virtually
      all clinics screen at least some clients for chlamydia; Planned Parenthood and
      Title X-funded clinics, more than others, tend to focus screening efforts on
      sexually active women aged 25 and younger. Single-dose treatments are provided by
      58% of clinics. Nine in 10 clinics offer HIV testing on-site, most of them to any
      client who requests it. Services targeted to specific populations include
      counseling about abstinence for minors (91%); non-reproductive health services
      for men (36%); and availability of staff such as translators (81%) and bilingual
      administrative (59%) or clinical personnel (57%) for non-English-speaking
      clients. CONCLUSIONS: More public funding is imperative for clinics to keep up
      with the demands of new technologies and a diverse client base.

PMID- 16963388
TI  - Promoting female condom use to heterosexual couples: findings from a randomized
      clinical trial.
AB  - CONTEXT: The female condom remains the only female-initiated method for
      preventing pregnancy and STDs, including HIV. Innovative methods for promoting
      its use, and for involving male partners in its use, are needed. METHODS: A
      sample of 217 women and their main male sexual partners were randomly assigned to
      one of three study conditions: a six-session relationship-based STD prevention
      intervention provided to the couple together, the same intervention provided to
      the woman only or a single-session education control provided to the woman only.
      Assessments were conducted at baseline and three months postintervention.
      Contrast coding was used to examine whether the effects of the two active
      interventions differed from those of the control intervention, and whether the
      effects of the two active interventions differed from each other. Regression
      analyses were used to estimate treatment effects. RESULTS: During follow-up,
      participants in either active intervention were more likely to use a female
      condom with their study partner and with all partners, and used female condoms at
      a higher rate with all partners, than individuals assigned to the control
      intervention; at the end of three months, they were more likely to intend to use
      the condom in the next 90 days. No significant differences in outcomes were found
      between the active intervention groups. CONCLUSIONS: Focusing on both a woman and
      her main male sexual partner is efficacious in increasing female condom use and
      intention to use among heterosexual couples at risk for HIV and other STDs.

PMID- 16963389
TI  - Do U.S. family planning clinics encourage parent-child communication? Findings
      from an exploratory survey.
AB  - CONTEXT: Clinics that receive Title X funding have a mandate to encourage parent
      child communication for minors seeking family planning services. Little is known
      about the programs and practices that clinics have adopted to achieve this goal,
      or whether clinics not receiving Title X funds encourage family participation.
      METHODS: As part of a larger project examining parental engagement among
      adolescents using family planning clinics, 81 clinics that served 200 or more
      adolescent contraceptive clients in 2001 completed a questionnaire containing
      closed- and open-ended items. Topic areas included clinic counseling and policies
      regarding clients younger than 18, activities to improve parent-child
      communication and community relations. Frequency distributions were calculated
      for the prevalence of activities, and cross-tabulations were used to compare
      prevalence by clinic characteristics. RESULTS: Every clinic engaged in at least
      one activity to promote parent-child communication, and nine in 10 offered
      multiple activities. Most of the clinics used counseling sessions to talk to
      adolescent clients about the importance of discussing sexual health issues with
      parents (73-94%, depending on the reason for the visit). More than eight in 10
      clinics (84%) distributed pamphlets on how to talk about these issues. A
      substantial minority (43%) offered or referred interested individuals to
      educational programs designed to improve communication. Some of these exploratory
      findings reflect the prevalence of activities among all U.S. family planning
      clinics that serve adolescent clients. CONCLUSIONS: Evaluation and expansion of
      clinic efforts to promote voluntary communication about sexual health issues
      between parents and children could help encourage family participation.

PMID- 16963390
TI  - Unprotected sex among youth living with HIV before and after the advent of highly
      active antiretroviral therapy.
AB  - CONTEXT: Since the advent of highly active antiretroviral therapy (HAART) in
      1996, the incidence of HIV-especially among young men who have sex with men-and
      the prevalence of unprotected sex among HIV-positive persons have increased. The
      characteristics associated with unprotected sex among youth living with HIV since
      the advent of HAART have not been explored. METHODS: Samples of HIV-positive
      youth aged 13-24 were taken from two intervention studies that targeted the
      sexual behaviors of HIV-positive youth-one from 1994 to 1996 (pre-HAART) and the
      other from 1999 to 2000 (post-HAART). Generalized estimating equations were used
      to identify characteristics associated with unprotected sex in each sample.
      RESULTS: The prevalence of unprotected sex in the post-HAART sample was more than
      twice that in the pre-HAART sample (62% vs. 25%). Among the pre-HAART sample,
      being a man who has sex with men and having sex with a casual partner were
      negatively associated with the odds of unprotected intercourse (odds ratios, 0.5
      and 0.2, respectively). Among the post-HAART sample, unprotected sex was
      negatively associated with knowing that a partner was HIV-negative (0.2) and
      positively associated with poorer mental health (1.02). In analyses among the
      post-HAART sample, poorer mental health was associated with increased odds of
      unprotected sex among youth living with HIV who were not receiving the treatment
      (1.02). CONCLUSIONS: Interventions for HIV-positive youth must be designed to
      address the complex needs of those youth who simultaneously suffer from HIV and
      poor mental health.

PMID- 16963391
TI  - The effects of rituximab treatment during pregnancy on a neonate.
AB  - A 35-year old woman developed Burkitt's lymphoma and was treated with rituximab
      and CHOP therapy early during pregnancy. Monitoring of rituximab concentrations
      and B-cell counts in the child revealed a transient complete B-cell depletion
      associated with high rituximab cord blood concentrations. B-cell recovery was
      fast, showing a regular immunophenotype without loss of CD20 antigen, no
      functional deficits and adequate vaccination IgG titers.

PMID- 16963392
TI  - Low-dose methotrexate as salvage therapy for refractory graft-versus-host disease
      after reduced-intensity conditioning allogeneic stem cell transplantation.
AB  - This study investigated the use of low dose methotrexate (MTX) (5 mg/m2/infusion)
      for the treatment of graft-versus-host disease (GVHD), after failure of
      corticosteroids. Twelve patients had refractory acute GVHD, while eight received
      MTX for severe chronic GVHD and/or the side effects of corticosteroids. Thirteen
      patients responded to MTX with six complete remissions and little toxicity,
      suggesting that low dose MTX is beneficial in refractory GVHD and deserves
      further investigations.

PMID- 16963395
TI  - Risk factors for death in patients with beta-thalassemia major: results of a case
      control study.
AB  - This retrospective one to one matched case-control study was aimed at evaluating
      risk factors for death in beta-thalassemic patients followed in Italian centers
      between 1997 and 2001. The mortality risk was lower in patients with good
      compliance to iron chelation therapy and in those treated with deferiprone.

PMID- 16963396
TI  - The role of race, socioeconomic status, and distance traveled on the outcome of
      African-American patients with multiple myeloma.
AB  - The incidence and mortality of multiple myeloma (MM) in African-Americans is
      double that in whites. We questioned whether race, socioeconomic status, and
      distance traveled affect overall survival. In a retrospective review of the
      records of 292 patients with MM. We found that the median age was 60 years and 38
      patients were African-Americans. The mean distance traveled was 67.7 miles. The
      median overall survival was similar in African-Americans and whites. Race,
      distance traveled and socioeconomic status were not independent prognostic
      factors for overall survival. In conclusion, socioeconomic status, distance
      traveled and race did not affect outcomes of MM patients treated at a specialized
      myeloma center.

PMID- 16963397
TI  - Long-term follow-up of children treated for acute lymphoblastic leukemia and the
      recovery of beta-cell function.
AB  - We studied the evolution of beta-cell function in 32 children treated for acute
      lymphoblastic leukemia (ALL) through a long-term follow-up after completion of
      therapy. Our results show that although alterations of the glucose metabolism
      persists after stop-therapy they are reversible with time.

PMID- 16963398
TI  - Effects of a Helicobacter pylori eradication regimen on anti-platelet
      autoantibody response in infected and uninfected patients with idiopathic
      thrombocytopenic purpura.
AB  - Thirty-seven patients with idiopathic thrombocytopenic purpura (ITP) were treated
      with a standard Helicobacter pylori eradication regimen irrespective of H. pylori
      infection. Our results indicate that platelet recovery results from the
      disappearance of H. pylori itself, and is mediated, in part, through suppression
      of anti-platelet autoantibody production.

PMID- 16963399
TI  - Beta-thalassemia in the indigenous population of Brittany: identification of
      three rare mutations.
AB  - Beta-thalassemia mutations were determined in ten Breton probands using a reverse
      hybridization method or denaturing gradient gel electrophoresis and sequencing.
      Six different mutations were found: three from the Mediterranean area and three
      rare. Mutations responsible for beta-thalassemia in Brittany are quite
      heterogeneous. The mutation in the initiation codon ATG-->ACG was found in four
      families and may result from an ancient founder effect, as suggested by the
      haplotype analysis.

PMID- 16963400
TI  - Karyotype complexity and VH gene status in B-cell chronic lymphocytic leukemia.
AB  - B-cell chronic lymphocytic leukemia-related genomic changes were analyzed by
      karyotyping, fluorescence in situ hybridization, and V(H) gene sequencing in a
      prospective clinical evaluation. The V(H) mutational status correlated with high
      risk cytogenetic aberrations while no such relation could be demonstrated for
      specific VH gene usage (V(3-21) and V(1-69)). Complex karyotypes were highly
      indicative of disease progression.

PMID- 16963401
TI  - Who cares for the carers?

PMID- 16963402
TI  - A Review: carers, MND and service provision.
AB  - Carers of people with MND may experience changes to their health and lifestyle.
      Statutory and voluntary organizations are able to support the carer in various
      ways. This review investigates the personal impact on carers and their
      experiences of service provision. A systematic search of online and grey
      literature was made for the period 1994-2004. Thirty-two key texts were retrieved
      and a narrative synthesis conducted. The main themes were: 1) Impact on carer:
      general health, emotional state, life satisfaction, socio-economic concerns,
      relationships, and protective factors; 2) Experience of service provision:
      primary care, health professionals, social care, written information, and
      voluntary organizations. There is a paucity of written documentation on the
      experience of assisting someone with MND. Data collected are diverse and
      sometimes contradictory. Sample sizes are often small and generalization
      difficult. Main findings show that maintenance of social support, activities, and
      a positive outlook may lessen the chance of ill health arising from long hours
      spent caring, and having a named coordinator may assist with access to resources,
      and provide practical and emotional support during and after the caring role.
      Carers may become ill themselves unless adequate support is given to them
      throughout the course of the disease.

PMID- 16963403
TI  - Clinical phenotypes of a large Chinese multigenerational kindred with autosomal
      dominant familial ALS due to Ile149Thr SOD1 gene mutation.
AB  - About 10% of amyotrophic lateral sclerosis (ALS) cases are familial. We
      identified a five-generation Chinese family with autosomal dominant familial ALS
      (FALS). We performed a detailed family study, clinical and electromyographic
      validation, and SOD1, VEGF and CNTF mutation analyses. Forty-five living members
      (16 affected) were studied and DNA samples collected. Genealogical data were
      collected for deceased members. Based on the duration between symptom onset to
      ventilator dependence, they were divided into rapidly progressive (range 1-18
      months, mean (SD) duration = 12.08 (+/-6.10) months, mean (SD) age of symptom
      onset = 39.75 (+/-9.84) years) and slowly progressive groups (>18 months; mean
      (SD) age of onset = 37.25 (+/-5.32) years old). We identified a heterozygous
      mutation of ATT to ACT of SOD1 gene at codon 149 in exon 5 resulting in
      substitution of isoleucine to threonine. It co-segregated with all affected
      members and 11 non-symptomatic members. We report a large multigenerational
      Chinese FALS kindred with I149T mutation in SOD1. No polymorphisms or mutations
      were found to date in two known modifier genes, namely, VEGF and CNTF, which were
      associated with heterogeneity in the phenotype within this kindred. Follow-up of
      the family will be helpful to explore any potential disease markers.

PMID- 16963404
TI  - Neuropsychological changes in patients with primary lateral sclerosis.
AB  - Primary lateral sclerosis (PLS) has been defined as rare, and the
      neuropsychological changes remain poorly defined. We studied 20 patients with a
      diagnosis of PLS. We carried out an extensive psychometric testing including a
      general assessment (memory, language, attention, visual-constructional ability
      and praxis) and a more specific assessment of prefrontal and premotor cortex
      functions in order to characterize the neuropsychological profile of the patients
      compared to matched controls, and explore executive functions and premotor cortex
      functions. None of the PLS patients was demented but they all presented memory
      deficits reflecting an executive dysfunction. All patients but three had signs of
      premotor and/or prefrontal cortex deficits. The cognitive impairment in PLS,
      specifically related to a frontal lobe dysfunction, seems qualitatively similar
      to ALS. Our results suggest a patchy distribution of cortical involvement in PLS
      but it remains difficult to draw any definite conclusion as to the spatio
      temporal progression of the disease into the different regions of the frontal
      lobe.

PMID- 16963405
TI  - How does current care practice influence the experience of a new diagnosis of
      motor neuron disease? A qualitative study of current guidelines-based practice.
AB  - Management during the diagnostic phase of MND is considered an important
      influence on the patient's further disease course. Guidelines for the management
      of MND have been developed, but little is known on how recommended practices
      influence patients' experience of a new diagnosis of MND. We undertook an
      interview-based study exploring issues surrounding the diagnosis of MND in a
      sample of consecutive patients recently diagnosed at a neurosciences centre. Data
      were analysed with Interpretative Phenomenological Analysis (IPA). Thirteen
      patients were recruited to the study. The major themes identified in descending
      order were 'Family/carers', 'Communication of the diagnosis', 'Reaction to the
      diagnosis', 'Physical difficulties', 'Time before diagnosis', 'Information',
      'Future', 'Coping with the diagnosis' and 'Formal support'. Communication was
      perceived satisfactory if handled according to existing guidelines. Physical
      difficulties impacted considerably on patients' lives. Delays in the diagnostic
      process appeared in various interviews. Five patients were avoiding information
      following the diagnosis. Some patients commented on an increasing number of
      uncoordinated services becoming involved after their diagnosis. This study
      supports the current international guidelines for MND care around diagnosis from
      the patients' perspective and underlines the importance of a multi-disciplinary,
      coordinated approach for patients with MND from diagnosis onwards.

PMID- 16963406
TI  - Measurement of decline of functioning in persons with amyotrophic lateral
      sclerosis: responsiveness and possible applications of the Functional
      Independence Measure, Barthel Index, Rehabilitation Activities Profile and
      Frenchay Activities Index.
AB  - It is important not only to monitor the functional change during the course of
      ALS, but also to determine whether or not the available help is sufficient. This
      study was performed to determine which generic assessment instrument is most
      appropriate. A multicentre cohort of patients with ALS was followed for one year.
      At baseline, six months, and 1 year four instruments were used: Functional
      Independence Measure (FIM), Rehabilitation Activities Profile (RAP), Barthel
      Index (BI), and Frenchay Activities Index (FAI). The responsiveness of the
      measures was examined using effect sizes and standardized response mean
      statistics. Seventy-three patients at baseline, 63 after six months and 43 after
      one year were assessed. If calculated on the group that completed all three
      assessments, the FIM, BI, and RAP showed moderate effect sizes and standardized
      response means over a period of six months and large effect sizes over 12 months.
      Based on their responsiveness FIM, BI, and RAP can be used to evaluate
      limitations in activities and care needs of persons with ALS and to evaluate
      treatment results in trials. The FIM was the most responsive instrument, although
      the BI might be easier to use in clinical practice.

PMID- 16963407
TI  - Analysis of factors that modify susceptibility and rate of progression in
      amyotrophic lateral sclerosis (ALS).
AB  - We conducted case-control and prospective longitudinal studies to examine risk
      factors and predictors of disease progression for ALS. Ninety-five subjects with
      ALS and 106 healthy control subjects were enrolled. All subjects completed a risk
      factor questionnaire at enrollment. The ALS subjects were prospectively followed
      for one year to define factors that influence the rate of disease progression,
      measured by rate of change in percent predicted forced vital capacity (%FVC) and
      the ALS functional rating scale (ALSFRS) score. The association of each potential
      risk factor with ALS was determined using univariate logistic regression. A
      random slope model was used to determine the association of each risk factor with
      disease progression. The demographic characteristics of ALS subjects and controls
      at enrollment did not differ. Significant risk factors for ALS included reported
      exposure to lead (p = 0.02) and pesticides (p = 0.03). Disease progression was
      faster in the ALS subjects having bulbar onset and a shorter time period between
      onset of symptoms and diagnosis. Pertinent variables not associated with either
      causation or progression of ALS included physical activity, cigarette smoking and
      a history of physical trauma or other clinical disorders.

PMID- 16963408
TI  - ALS: cytokine profile in cerebrospinal fluid T-cell clones.
AB  - T -cells are present in the spinal cord from patients with amyotrophic lateral
      sclerosis (ALS), and could attack neurons or activate microglia through secretion
      of cytokines. We report that interferon (IFN)-gamma, tumour necrosis factor (TNF)
      alpha, interleukin (IL)-2, IL-4, IL-5 and IL-10 could not be detected in
      cerebrospinal fluid (CSF) samples from 15 ALS patients and 23 out of 25 controls
      with a multiplexed cytometric bead assay. In vivo activated T-cell clones were
      established from CSF (n = 26) and blood (n = 21) of one ALS patient. The
      proliferative capacity of CSF T-cell clones was lower than that of T-cell clones
      from blood (p = 0.0007). All CD4+ CSF T-cell clones produced IFN-gamma,
      compatible with a predominant T helper (h) 1 phenotype, but several T-cell clones
      also produced Th2 cytokines. These data suggest that in vivo activated
      intrathecal T-cells can be induced to secrete cytokines which may play a role in
      ALS.

PMID- 16963409
TI  - Cardiac arrest in a patient with Brown-Vialetto-Van Laere syndrome.

PMID- 16963411
TI  - [Study on DAZ gene copy deletion in severe oligozoospermia sperm donor for ICSI].
AB  - Deletion of DAZ gene copies is related to spermatogenesis impairment. To
      investigate the distribution of DAZ gene copy deletions among Chinese men, we
      analyzed DAZ gene deletions by multiplex polymerase chain reaction (multi-PCR)
      and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      in 128 infertile patients with severe oligozoospermia selected as semen donors
      for intracytoplasmic sperm injection (ICSI) and 287 normospermic men. Three
      patterns of DAZ gene deletions, namely DAZ1/DAZ2 deletion, DAZ3/DAZ4 deletion and
      complete deletion of all 4 DAZ copies, were found in the present study. Complete
      deletion of the entire DAZ family of genes was only present in 11.7% of severe
      oligozoospermic patients. The frequency of DAZ1/DAZ2 deletion was significantly
      higher in severe oligozoospermic patients than that in the controls(9.4% vs 2.8%,
      P = 0.004. The total frequency of complete DAZ deletion and DAZ1/DAZ2 deletion
      was 21.1%. No significant difference in the frequency of DAZ3/DAZ4 deletion was
      observed between the patient and control group (7.0% vs 3.8%, P > 0.05). These
      results suggest that complete DAZ deletion is a frequent genetic cause of severe
      oligozoospermia, and DAZ1/DAZ2 deletion is a high risk factor for the disease.
      Thus, it is necessary to screen the two deletion patterns of DAZ genes in
      severely oligozoospermic sperm donors before ICSI during assisted reproduction.

PMID- 16963412
TI  - [Methylation status of the 5' CpG islands in FHIT gene in the plasma and tissues
      of cervical cancer patients].
AB  - To evaluate the methylation status of the 5' CpG islands in FHIT gene using
      plasma and tissue samples from cervical cancer patients and find a novel marker
      for non-invasive diagnosis of cervical cancer, methylation-specific PCR (MSP) was
      employed to examine CpG island methylation in FHIT gene in 151 pretreatment
      plasma samples and 30 tumor tissue samples obtained from cervical cancer
      patients. MSP product was cloned and sequenced directly. CpG island methylation
      of FHIT was detected in 31.13% of the plasma samples, and in 53.33% of the tissue
      samples. The total concordant rate of methylation status between plasma and
      tissue samples in FHIT gene was 80.00%. We found a strong positive correlation
      between FHIT methylation in the plasma and the clinical stage and histological
      grade of the tumor. The data showed that CpG island methylation of the FHIT gene
      is prevalent in the plasma and tissue samples from cervical cancer patients. FHIT
      detection may be used as a non-invasive marker for diagnosis of cervical cancer
      and prognostic treatment evaluation.

PMID- 16963413
TI  - [Analysis of the mode of inheritance in familial bronchial asthma].
AB  - To study the mode of inheritance of familial bronchial asthma and to understand
      the population genetics laws of bronchial asthma, Families with a family history
      of bronchial asthma in Handan region were investigated using group research
      method. The xi2 test of the degree of coincidence between the expected and
      observed values was analyzed by pedigree analysis and the "Smith" agonic revise
      method. The incidence rate within the 72 families pedigree with familial
      bronchial asthma, including 109 core pedigrees, is 0.46. Analysis shows a
      tendency towards single gene inheritance. Pedigree analysis reveals that it is
      consistent with autosome dominant inheritance. Analysis of the D- x dd marriage
      with the "Smith" analytical method supports this conclusion (xi2 = 3.181, P >
      0.05) and further hints there exists genetic heterogeneity, i.e. different modes
      of inheritance among different marriage types. Our results can offer the
      reference to the prevention, diagnosis and treatment of familial bronchial
      asthma.

PMID- 16963414
TI  - [PCR-SSCP polymorphism of FSHbeta gene and its relationship with prolificacy of
      Jining grey goats].
AB  - The follicle-stimulating hormone beta-subunit (FSHbeta) gene was studied as a
      candidate gene for the prolificacy in Jining Grey goats. According to the
      sequence of ovine FSHb gene, nine pairs of primers were designed to detect single
      nucleotide polymorphisms of 5' regulatory region, exon 1 and exon 2 of FSHbeta
      gene in both high fecundity breed (Jining Grey goat) and low fecundity breeds
      (Liaoning Cashmere goat, Boer goat and Angora goat) by PCR-SSCP. The results
      indicated that the homology of nucleotide sequence of this fragment between goat
      and sheep was 98 percent. Only the products amplified by primer P9 displayed
      polymorphism. Three genotypes (AA, AB and AC) were detected in Jining Grey goats
      and Liaoning Cashmere goats. Three genotypes (AA, CC and AC) were detected in
      Boer goats. Six genotypes (AA, BB, CC, AB, AC and BC) were detected in Angora
      goats. Sequencing revealed a G-->A mutation at 94 bp of exon 2 of FSHbeta gene in
      the BB genotype in comparison to the AA genotype and a C-->T mutation at 174 bp
      of exon 2 of FSHbeta gene in the CC genotype in comparison to the AA genotype.
      The former mutation resulted in an amino acid change: alanine-->threonine, and
      the latter mutation did not cause any amino acid change. Genotype frequency of
      AA, AB and AC was 0.686, 0.137 and 0.177 in Jining Grey goats, respectively. The
      does with genotype AA had 0.78 (P<0.05) or 0.64 (P<0.05) kids more than those
      with genotype AB or AC in Jining Grey goats, respectively.

PMID- 16963415
TI  - [The developmental patterns of GH-R, IGF-1 and IGF-IR gene expression in sheep
      skin].
AB  - Semi-quantitative RT-PCR was applied to investigate the developmental patterns of
      GH-R, IGF-1 and IGF-IR mRNA expression in skin of two sheep breeds. One breed was
      the first filial generation (F1) of Romilly Hillys x Merino of China (Xinjiang
      Agricultural Reclamation line) wool sheep, and the other was Kazak hair sheep.
      18S rRNA was used as the internal standard. Sheep were weighed and wool and skin
      samples were collected at different times. Results showed that body weight
      increased rapidly during 30-135 days but slowed during 135-255 days. Wool growth
      increased gradually during 30-135 days, degreased till 180 days of age, but
      rebounded thereafter. Overall, body weight and developmental patterns of wool
      growth was not significant different between hair and wool sheep. GH-R mRNA
      expression in the skin of hair sheep increased significantly during 30-90 days,
      peaked at 90 days of age (P<0.05), then declined signifi cantly (P<0.05). GH-R
      mRNA expression in the skin of wool sheep increased significantly until 135 days
      of age (P<0.01) and then decreased significantly (P<0.01). The peak level was
      higher in the wool sheep than the hair sheep. The expression of cantly IGF-1 mRNA
      and IGF-IR mRNA in the skin of hair sheep increased during 30-90 days, then
      declined significantly (P<0.01). The expression of IGF-1 mRNA and IGF-IR mRNA in
      the skin of wool sheep were high at birth and then reduced gradually. The IGF-1
      mRNA expression in the skin of hair sheep reached its peak at 90 days of age, and
      was significant higher than that of wool sheep. The expression of GH-R, IGF-1 and
      IGF-IR mRNA in skin of hair sheep was higher than that of wool sheep before 90
      days of age, but was lower after that. The results suggest that GH-R, IGF-1 and
      IGF-IR mRNA expression in the skin of sheep follows specific developmental
      patterns, and different patterns exist between the two breeds.

PMID- 16963416
TI  - [Influence of maternal genetic effect on genetic parameter estimates of
      production traits of cashmere goat].
AB  - The derivative-free restricted maximum likelihood (DFREML) method was used to
      compare the differences of genetic parameter estimates of Inner Mongolian
      Cashmere Goats under two models, which differ in whether maternal genetic effect
      is taken into account. The differences between the two models were, tested by
      likelihood ratio test. The results show that maternal genetic effect highly
      affects live body weight and cashmere thickness while has no significant effect
      on raw cashmere weight, staple length, fibre diameter and fibre length.

PMID- 16963417
TI  - [Molecular cloning and homologous modeling of Wulong goose MHC class I gene].
AB  - Major histocompatibility complex (MHC) was correlated with immune response for
      extra-antigen. MHC sequences of chicken, other birds, crawl species and mammalian
      were derived from GenBank/DDBJ/EMBL and analyzed by alignment, and then primers
      were designed. By means of LA-PCR method, MHC Classgene was cloned from Wulong
      goose genomic DNA and total RNA, and the structure of MHC Classgenomic DNA was
      analyzed using bioinformation methods. The results showed that the genomic DNA,
      which consisted of 8 extrons and 7 introns, had 64.1% amino acids homologous to
      chicken and 42.9% amino acids to human. The molecular phylogenetic tree further
      revealed evolutionary relationship between Wulong goose and other animals such as
      chicken, other birds, crawl species, mammalian and human. The results of
      homologous modeling showed that Wulong Goose MHC Classgene was formed by
      amidocyanogen (N) terminal structure region and carboxyl (C) terminal structure
      region.

PMID- 16963418
TI  - [Genetic diversity of Dactylis glomerata germplasm resources detected by Inter
      simple Sequence Repeats (ISSRS) molecular markers].
AB  - Inter-simple Sequence Repeat (ISSR) molecular markers were used to detect the
      genetic diversity among 50 materials of Dactylis glomerata collected from China
      and other countries. Twelve primers produced 101 polymorphic bands, averaged 8.41
      bands each primer pair. The average percentage of polymorpgic bands was 86.3.8%,
      and the range of GS (define) was 0.6116-0.9290, indicating a rich genetic
      diversity of D. glomerata. Based on the cluster and principal component analyses
      on the genetic characteristics, D. glomerata could be divided into 5 groups
      according to the nearest phylogenetic relationship. In most cases, accessions
      from the same continent were classified into the same group, the accessions from
      China and the United States belong to the different groups, respectively,
      indicating the geographical distribution of genetic diversity of D. glomerata.
      The present paper also discussed collection and conservation of germplasm
      resources in D. glomerata.

PMID- 16963419
TI  - [Screening the genes associated with anthocyanin biosynthesis in roots of 'Tsuda'
      turnip using cDNA microarray].
AB  - Anthocyanins are important secondary metabolites in plants, which are involved in
      many functions. The white peel of an enlarged root in 'Tsuda' plants turned red
      after irradiated with UV-A light for 48 h, but remained white when held in the
      dark. Red earthnuts and white peels were hybridized with cDNA microarray made by
      unique gene fragments of subtraction library. The expression of 81 genes were up
      regulated including cytochrome P450, PAL, F3H, ANS, CHS, DFR and GST gene
      fragments related to anthocyanidin biosynthesis. The expression of 47 genes was
      down-regulated after irradiated with UV-A light. The northern blotting results
      showed that the expression of PAL, CHS, F3H, DFR and ANS in red root peels was
      more in 'Tsuda' turnip after irradiation with UV-A light than in white ones held
      in a dark condition. The results of northern blotting verified the reliability of
      cDNA microarray.

PMID- 16963420
TI  - [A SCAR marker for resistance to Aspergillus flavus in peanut (Arachis hypogaea
      L.)].
AB  - Aflatoxin contamination is an important constraint to peanut (Archis hypogaea L.
      ) industry worldwide. Genetic improvement for host resistance in peanut to fungal
      infection and aflatoxin (Aspergillus flavus) production is among the approaches
      for integrated management of the problem. However, the progress in peanut
      breeding for resistance to aflatoxin is slow due to various reasons, among which,
      lack of cost-effective method for resistance identification in breeding materials
      or segregating progenies has been encountered in most breeding programs. Hence
      there is a need to develop a rapid and reliable screening method for selecting A.
      flavus infection resistance in peanut. Here we report a SCAR (Sequence
      characterized Amplified Region) marker "AFs-412" converted from AFLP (amplified
      fragment length polymorphism) marker "E45/M53-440" which closely linked with
      resistance to A. flavus infection. Twenty peanut genotypes with resistance to
      infection of A. flavus were used to verify the reliability of the resistance
      markers, and high correlation between the molecular markers and the resistance
      result. The result shows that the potential of the markers which can be used in
      other resistant peanut genotypes to seed infection by Aspergillus flavus.

PMID- 16963421
TI  - [Crude extraction and activity assay of CEL I].
AB  - CEL I, extracted from celery, is the first known eukaryotic nuclease that cleaves
      DNA with high specificity at sites of base-substitution mismatch and DNA
      distortion. It is a key enzyme for TILLING research. Here we reported a crude
      extraction method and activity assay of CEL I. Incision at mismatches of single
      nucleotide suggested that CEL I can effectively detect DNA at G-->A base
      substitution and the result can be obtained from an ABI377 Sequencer. Therefore,
      the extracted enzyme can be used in TILLING.

PMID- 16963422
TI  - [Bayesian statistics-based method for genetic linkage analysis].
AB  - Bayesian School as one of the important statistical schools is different from the
      Classical Statistics, and the Bayesian methods have been widely used in many
      fields of modern sciences. In the present paper, we discussed the application of
      Bayesian method in linkage analysis, including the Bayesian estimation of
      recombination fraction, linkage testing based on the Bayes Factor and the
      Bayesian approach for genetic linkage map construction via Markov chain Monte
      Carlo algorithm. Simulation study and real data analysis were performed using
      SAS/IML software, and the validity and practicability of Bayesian method in
      genetic linkage analysis were thus verified.

PMID- 16963423
TI  - [Synthesis of total sFat-1 gene by PCR-restrict enzyme ligation method].
AB  - Gene synthesis is very important in life science research, and it becomes a
      technique in common use. It is difficult for long gene synthesis, because the
      mismatches and mutations of DNA sequence in nucleotide fragments assembling. This
      study established a new method for long gene synthesis, which was referred to as
      PCR-restrict enzyme ligation method. With this method, a omega-3 fatty acid
      desaturase gene, sFat-1, from Caenorhabditis briggssae, was successfully
      assembled from 27 synthesized nucleotide fragments (60 ~ 68 bp for each fragment
      ) following 3 rounds of PCR (7 reactions) and 2 rounds of restrict enzyme
      ligation (3 reactions). This shows that the PCR-restrict enzyme ligation method
      is an effective method for long gene synthesis.

PMID- 16963424
TI  - [Analysis of diffuse large B-cell lymphoma heterogeneity based on coupled two-way
      clustering].
AB  - Microarray technology has proposed a powerful tool in dealing with the
      heterogeneity of disease. Currently, many methods in the field are based on
      traditional hierarchical clustering to discover subtypes of disease using a large
      number of genes on microarray.However, they did not considered that large
      unrelated noise (genes)may mask significant partitions and correlations of
      disease samples. To avoid the shortcoming, this paper presented a heterogeneous
      analysis based on coupled two-way clustering (HCTWC) to search interesting gene
      signature and find the natural partitions of disease samples. The method was
      applied to diffuse large B-cell lymphoma (DLBCL) microarray dataset. By
      identifying significant gene signature, we were able to discover the two new
      subtypes of DLBCL with survival rate 55% and 25% respectively. The results showed
      that HCTWC had the potential to be a powerful tool for solving the heterogeneity
      of disease on gene expression profile.

PMID- 16963425
TI  - [The informatics of human genome and traditional Chinese medicine].
AB  - Guided by the theory and methodology of yin-yang set derived from Changing Book
      and Medicine Canon, and using genetics as a bridge, we have tried to bring
      together the ancient functional systematology and modern structural one as well
      as Eastern and Western medicine, thereby promoting the modernization of
      traditional Chinese medicine (TCM) in theory and in clinical practice. Herein, we
      used virtual technology to transform the genetic information in OMIM of NCBI
      (National Center for Biotechnology Information of USA,
      http://www.ncbi.nlm.nih.gov ) into a secondary database in the form of webpages.
      There are sixteen kinds of the database named gene morbidity ones as followings
      as: the nature of gene, the profile of common phenotype, a interaction of
      endogenous, the disease of a organ or a viscera pathogenesis phenomenon, TCM, the
      sign of diagnosis of western medicine, the gene response to environment,
      syndrome, disease, nerve and -endocrine, tumor and cancer, psychology and
      behavior, morbidity, endo-factor of molecular information, expression, the
      interaction between endogenous and exogenous in which there is 4 711 words,
      files. The advantages of the database are its aptness for using human fuzzy
      intelligence to recognize things, suitability to uncovering the noumenon
      (yinyang) nature of an object and applicability to clinical use.

PMID- 16963426
TI  - [Progress on breast cancer metastasis suppressor 1 (BRMS1)].
AB  - Tumour metastasis is a significant contributor to death in cancer patients. So
      studies on the molecular mechanism of tumor metastasis can provide new prognostic
      and therapeutic methods. Tumor metastasis suppressor gene is a kind of genes that
      only suppresses metastasis without affecting tumorigenicity and tumor growth.
      BRMS1 is a tumor metastasis suppressor gene discovered in breast carcinoma cells
      in 2000. Its protein product was found to also suppress metastasis of melanoma
      cells and murine mammary carcinoma cells. BRMS1 is located in the nucleus,and
      interacts with mSin3-HDAC complex, and can alter the connexin expression profile
      of breast carcinoma cells, thereby restoring cell-cell communication via gap
      junctions. This review highlights some recent progress in the study of BRMS1,
      gives a brief introduction of related genes, and predicts its possible mechanism
      of action.

PMID- 16963427
TI  - [A new form of Oculocutaneous albinism, OCA4].
AB  - Oculocutaneous albinism (OCA) is a complex genetic disease with great clinical
      heterogeneity. Four different types of OCA have been reported to date (OCA1,
      OCA2, OCA3, and OCA4). OCA4 was firstly reported in a Turkish OCA patient. The
      gene responsible for OCA4 is the human homologue of the mouse underwhite (uw)
      gene, which encodes the mem-brane-associated transporter protein (MATP). MATP
      gene is located on chromosome 5p13.3 and is divided into 7 exons and 6 introns.
      MATP gene is transcriptionally modulated by MITF, and encodes a protein of 530
      amino acids. There are at least 18 pathologic mutations and 8 non-pathologic
      polymorphisms have been found.

PMID- 16963428
TI  - [Functions of Y-box binding protein and its role in tumorigenicity].
AB  - Y-box binding proteins, belonging to a family of multifunctional proteins
      conserved from bacteria to human, are involved in transcriptional and
      translational regulation of various genes, mRNA alternative splicing, DNA
      replication and repair, as well as cell proliferation. A typical Y-box binding
      protein contains three structure domains, namely the N-terminal domain, the
      hydrophilic C-terminal domain and the conserved cold shock domain (CSD) which
      binds strongly to inverted CCAAT box found in different promoters and determines
      protein function.Y-box binding proteins may play an important physiological role
      in cell proliferation.For example, the human Y-box protein 1 (YB-1) may be
      repressed in the oncogenic phosphoinositide 3-kinase (PI3K) pathway. In addition,
      it may also act as a negative regulator of p53. It has been demonstrated that YB
      1 represses transcription of the p53 promoter in a sequence-specific manner using
      specifically reporter assays. This implies that YB-1 may, in some situations,
      protect cells from p53-mediated apoptosis, indicating that YB-1 may be a good
      target for the development of a new therapeutics.The function of Y-box binding
      protein and its effect on carcinogenesis are summarized in the paper. We hope to
      further explore the functional roles of Y-box binding protein, and provide some
      helpful lines and suggestions for tumor control.

PMID- 16963429
TI  - [The development of rapid screening of colorectal cancer by mutation detection in
      fecal DNA].
AB  - Colorectal cancer is one of the leading causes of death in the world. Screening
      high-risk populations for colorectal cancer can lower both the incidence of and
      deaths from the disease. Mutation detection in fecal DNA is a new approach of
      screening patients for colorectal cancer. Compared with colonoscopy and fecal
      occult-blood test, this approach has the advantages of high specificity, high
      sensitivity and general acceptability. This paper systematically reviewed genes
      associated with fecal DNA testing, methods for extracting tumor-specific DNA, and
      methods for detecting gene mutations. Moreover, the application of mutation
      detection using fecal DNA for rapid screening of colorectal cancer was briefly
      discussed.

PMID- 16963430
TI  - [Cytogenetics and application in domesticated silkworm Bombyx mori].
AB  - Chromosome identification and karyotype analyses of Bombyx mori (Lepidoptera)
      have long been hampered by the high number and the absence of suitable markers,
      such as centromeric position and chromosome bands. Recently, the cytological map
      has been constructed using comparative genomic hybridization-genomic in situ
      hybridization and BAC-based fluorescence in situ hybridization. Dense cytogenetic
      maps are being constructed by integrating cytological map with molecular linkage
      maps. Molecular and cytogenetics will help us to reveal the structure and
      function of chromosome of Bombyx mori, the W chromosome is composed largely of
      dense nested retrotransposons, and telomeres are consist of the TTAGG motifs and
      two type of telomere-specific non-LTR retrotransposons (TRAS1 and SART1), the
      TRAS1 and SART1 with abundant transcription activity may be involved in the
      stabilization of chromosomal ends.

PMID- 16963431
TI  - [Comparison of early embryogenesis between silkworm and Drosophila from both
      morphology and gene content level].
AB  - The diversity of insects has been the focus of many investigations. Research in
      the early embryonic developmental mechanism of silkworm will promote
      understanding in early embryonic developmental mechanism of other insects. This
      paper reviews the differences in early embryonic development of silkworm and
      Drosophila from both morphology and gene content level. The results not only
      provide evidences for the study of early embryonic development mechanism in
      silkworm, but also give clues for the study of insects diversity.

PMID- 16963432
TI  - [The structure, function and recent reseach of pRNA].
AB  - In the bacteriophage phi29, a virus-encoded RNA(pRNA) is required for the
      packaging of its genomic DNA. Six pRNAs form a hexamer through pRNA/pRNA
      interaction to drive the DNA translocation motor, and ATP as the energy resource.
      Chimeric pRNAs can steadily combine with siRNA, ribozymes and anti-sense RNA, and
      then be transferred into the cancer cells and viral-infected cells by RNA
      nanotechnology. The continued study of pRNA will help us to understand the origin
      of the life and explore its possible applications.

PMID- 16963433
TI  - [Variation of both DNA genetic structure and reproduction traits of plant
      autotetraploid].
AB  - Due to the effect of chromosome doubling, the DNA genetic structures of
      autotetraploid vary from its original diploid, and thus autotetraploid phenotype
      changes correspondingly. Compared with original diploid, the phenotype changes of
      autotetraploid were as follows. The part of its male and female gametes was of
      abortion. Its pollen (diplo-haplont) was significantly bigger. The number of egg
      cells or synergids or antipodal cells in its embryo sacs increases or reduces.
      While self-crossing procreation of it, pollen tubes and the fertilization
      processes of polar nucleus and the fertilized cells development were partly
      abnormal. Its reproductive capacity (or seed setting rate) dropped to some
      extents, which can be gradually improved with generations. For some plant
      species, it has a better cross-compatibility in distant hybridizations.

PMID- 16963434
TI  - [How long the way from QTL to QTGS?].
AB  - Most of the important economic traits in higher plants are quantitative traits.
      Genetic basic researches for quantitative traits were strongly promoted. This
      article fully elaborated the complicated relationship between quantitative
      phenotype and its genotype, introduced the recently developed strategy of fine
      mapping. discussed the current difficulty and hardness among the process of
      dissect the genetic basis of target traits, then brought forward several research
      direction that remained to be improved , and finally gave a view of such
      prospect. Generally speaking,, however, a QTL is still a considerable DNA
      fragment frequently containing multiplex genes. We also provided some ways and
      means from QTL coarse locus research to the variation at quantitative trait gene
      (QTG) level and from QTG to quantitative trait nucleotides (QTN) corresponding to
      alleles resulted from the intragenetic polymorphism. This is a major challenge
      for quantitative genetics in the post-genome era.

PMID- 16963435
TI  - TENORM aerosols in the Florida phosphate industry--assessment of lung fluid
      solubility and annual effective dose to workers.
AB  - Inhalation exposure to workers in the Florida phosphate industry due to TENORM
      aerosols has not been adequately addressed owing to lack of aerosol information.
      One of the more critical factors is the absorption rate of inhaled radionuclides
      into blood. In this study, this parameter was characterised using an in vitro
      dissolution test. The solubility data and other aerosol information were then
      used for individualised dose assessments at six different Florida phosphate
      facilities. The solubility data support the selections of ICRP Publication 66
      Type M for uranium and lead isotopes and Type S for thorium isotopes. Total
      annual effective doses are 0.34 +/- 0.12 mSv at granulator areas, 0.30 +/- 0.10
      mSv at storage areas and 0.23 +/- 0.02 mSv at shipping areas. These findings are
      considerably lower than originally postulated in previous studies where no site
      specific information on particle size and lung fluid solubility had been
      available.

PMID- 16963436
TI  - Evaluation of fat-free mass by whole-body counter in Japanese healthy young
      adults.
AB  - Whole-body counters (WBCs) are special instruments for measuring internal
      irradiation doses and are usually housed within or around nuclear facilities in
      the event of unexpected radiation emergencies. As a substantial proportion of
      total body potassium (TBK) is found in fat-free mass (FFM), FFM volume can be
      predicted from WBC-measured (40)K. We screened TBK in Japanese healthy young
      adults using a WBC and found strong linear correlations between TBK and lean body
      mass (LBM) and body mass index (r = 0.97, P < 0.01 and r = 0.47, P < 0.01,
      respectively). Multiple linear regression analysis, following adjustments for
      sex, indicates that only LBM has a significant correlation with TBK (P < 0.01).
      These results strongly support the feasibility of using WBCs for estimating FFM.

PMID- 16963437
TI  - Identification of a peroxisomal acyl-activating enzyme involved in the
      biosynthesis of jasmonic acid in Arabidopsis.
AB  - Jasmonic acid (JA) is a lipid-derived signal that regulates a wide variety of
      developmental and defense-related processes in higher plants. JA is synthesized
      from linolenic acid via an enzymatic pathway that initiates in the plastid and
      terminates in peroxisomes. The C18 JA precursor 12-oxo-phytodienoic acid (OPDA)
      is converted in the peroxisome to 3-oxo-2-(2'-[Z]-pentenyl)cyclopentane-1
      octanoic acid (OPC-8:0), which subsequently undergoes three rounds of beta
      oxidation to yield JA. Although most JA biosynthetic enzymes have been
      identified, several key steps in the pathway remain to be elucidated. To address
      this knowledge gap, we employed co-expression analysis to identify genes that are
      coordinately regulated with known JA biosynthetic components in Arabidopsis.
      Among the candidate genes uncovered by this approach was a 4-coumarate-CoA ligase
      like member of the acyl-activating enzyme (AAE) gene family, which we have named
      OPC-8:0 CoA Ligase1 (OPCL1). In response to wounding, opcl1 null mutants
      exhibited reduced levels of JA and hyperaccumulation of OPC-8:0. Recombinant
      OPCL1 was active against both OPDA and OPC-8:0, as well as medium-to-long
      straight-chain fatty acids. Subcellular localization studies with green
      fluorescent protein-tagged OPCL1 showed that the protein is targeted to
      peroxisomes. These findings establish a physiological role for OPCL1 in the
      activation of JA biosynthetic precursors in leaf peroxisomes, and further
      indicate that OPC-8:0 is a physiological substrate for the activation step. The
      results also demonstrate the utility of co-expression analysis for identification
      of factors that contribute to jasmonate homeostasis.

PMID- 16963438
TI  - Solution structures and backbone dynamics of a flavodoxin MioC from Escherichia
      coli in both Apo- and Holo-forms: implications for cofactor binding and electron
      transfer.
AB  - Flavodoxins play central roles in the electron transfer involving various
      biological processes in microorganisms. The mioC gene of Escherichia coli encodes
      a 16-kDa flavodoxin and locates next to the chromosomal replication initiation
      origin (oriC). Extensive researches have been carried out to investigate the
      relationship between mioC transcription and replication initiation. Recently, the
      MioC protein was proposed to be essential for the biotin synthase activity in
      vitro. Nevertheless, the exact role of MioC in biotin synthesis and its
      physiological function in vivo remain elusive. In order to understand the
      molecular basis of the biological functions of MioC and the cofactor-binding
      mechanisms of flavodoxins, we have determined the solution structures of both the
      apo- and holo-forms of E. coli MioC protein at high resolution by nuclear
      magnetic resonance spectroscopy. The overall structures of both forms consist of
      an alpha/beta sandwich, which highly resembles the classical flavodoxin fold.
      However, significant diversities are observed between the two forms, especially
      the stabilization of the FMN-binding loops and the notable extension of secondary
      structures upon FMN binding. Structural comparison reveals fewer negative charged
      and aromatic residues near the FMN-binding site of MioC, as compared with that of
      flavodoxin 1 from E. coli, which may affect both the redox potentials and the
      redox partner interactions. Furthermore, the backbone dynamics studies reveal the
      conformational flexibility at different time scales for both apo- and holo-forms
      of MioC, which may play important roles for cofactor binding and electron
      transfer.

PMID- 16963439
TI  - HIV gp120-induced interaction between CD4 and CCR5 requires cholesterol-rich
      microenvironments revealed by live cell fluorescence resonance energy transfer
      imaging.
AB  - Binding of the human immunodeficiency virus (HIV) envelope gp120 glycoprotein to
      CD4 and CCR5 receptors on the plasma membrane initiates the viral entry process.
      Although plasma membrane cholesterol plays an important role in HIV entry, its
      modulating effect on the viral entry process is unclear. Using fluorescence
      resonance energy transfer imaging, we have provided evidence here that CD4 and
      CCR5 localize in different microenvironments on the surface of resting cells.
      Binding of the third variable region V3-containing gp120 core to CD4 and CCR5
      induced association between these receptors, which could be directly monitored by
      fluorescence resonance energy transfer on the plasma membrane of live cells.
      Depletion of cholesterol from the plasma membrane abolished the gp120 core
      induced associations between CD4 and CCR5, and reloading cholesterol restored the
      associations in live cells. Our studies suggest that, during the first step of
      the HIV entry process, gp120 binding alters the microenvironments of unbound CD4
      and CCR5, with plasma membrane cholesterol required for the formation of the HIV
      entry complex.

PMID- 16963440
TI  - Crystal structures of nonoxidative zinc-dependent 2,6-dihydroxybenzoate (gamma
      resorcylate) decarboxylase from Rhizobium sp. strain MTP-10005.
AB  - Reversible 2,6-dihydroxybenzoate decarboxylase from Rhizobium sp. strain MTP
      10005 belongs to a nonoxidative decarboxylase family. We have determined the
      structures of the following three forms of the enzyme: the native form, the
      complex with the true substrate (2,6-dihydroxybenzoate), and the complex with 2,3
      dihydroxybenzaldehyde at 1.7-, 1.9-, and 1.7-A resolution, respectively. The
      enzyme exists as a tetramer, and the subunit consists of one (alphabeta)8 triose
      phosphate isomerase-barrel domain with three functional linkers and one C
      terminal tail. The native enzyme possesses one Zn2+ ion liganded by Glu8, His10,
      His164, Asp287, and a water molecule at the active site center, although the
      enzyme has been reported to require no cofactor for its catalysis. The substrate
      carboxylate takes the place of the water molecule and is coordinated to the Zn2+
      ion. The 2-hydroxy group of the substrate is hydrogen-bonded to Asp287, which
      forms a triad together with His218 and Glu221 and is assumed to be the catalytic
      base. On the basis of the geometrical consideration, substrate specificity is
      uncovered, and the catalytic mechanism is proposed for the novel Zn2+-dependent
      decarboxylation.

PMID- 16963441
TI  - Microtubules support production of starvation-induced autophagosomes but not
      their targeting and fusion with lysosomes.
AB  - Autophagy is a major catabolic pathway in eukaryotic cells whereby the lack of
      amino acids induces the formation of autophagosomes, double-bilayer membrane
      vesicles that mediate delivery of cytosolic proteins and organelles for lysosomal
      degradation. The biogenesis and turnover of autophagosomes in mammalian cells as
      well as the molecular mechanisms underlying induction of autophagy and
      trafficking of these vesicles are poorly understood. Here we utilized different
      autophagic markers to determine the involvement of microtubules in the autophagic
      process. We show that autophagosomes associate with microtubules and concentrate
      near the microtubule-organizing center. Moreover, we demonstrate that
      autophagosomes, but not phagophores, move along these tracks en route for
      degradation. Disruption of microtubules leads to a significant reduction in the
      number of mature autophagosomes but does not affect their life span or their
      fusion with lysosomes. We propose that microtubules serve to deliver only mature
      autophagosomes for degradation, thus providing a spatial barrier between
      phagophores and lysosomes.

PMID- 16963442
TI  - Alloreactivity between disparate cognate and allogeneic pMHC-I complexes is the
      result of highly focused, peptide-dependent structural mimicry.
AB  - Our understanding of the molecular mechanisms of T cell alloreactivity remains
      limited by the lack of systems for which both the T cell receptor allo- and
      cognate ligand are known. Here we provide evidence that a single alloreactive T
      cell receptor interacts with analogous structural regions of its cognate ligand,
      HLA-B*0801(FLRGRAYGL), as its allogeneic ligand, HLA-B*3501(KPIVVLHGY). The
      crystal structures of the binary peptide-major histocompatibility complexes show
      marked differences in the conformation of the heavy chains as well as the bound
      peptides. Nevertheless, both epitopes possess a prominent solvent-exposed
      aromatic residue at position 7 flanked by a small glycine at position 8 of the
      peptide determinant. Moreover, regions of close structural homology between the
      heavy chains of HLA B8 and HLA B35 coincided with regions that have previously
      been implicated in "hot spots" of T cell receptor recognition. The avidity of
      this human T cell receptor was also comparable for the allo- and cognate ligand,
      consistent with the modes of T cell receptor binding being broadly similar for
      these complexes. Collectively, it appears that highly focused structural mimicry
      against a diverse structural background provides a basis for the observed
      alloreactivity in this system. This cross-reactivity underpins the T cell
      degeneracy inherent in the limited mature T cell repertoire that must respond to
      a vast diversity of microbial antigens.

PMID- 16963443
TI  - Gs activation is time-limiting in initiating receptor-mediated signaling.
AB  - To analyze individual steps of G(S)-linked signaling in intact cells, we used
      fluorescence resonance energy transfer (FRET)-based assays for receptor-G protein
      interaction, G protein activation, and cAMP effector activation. To do so, we
      developed a FRET-based sensor to directly monitor G(S) activation in living
      cells. This was done by coexpressing a Galpha(s) mutant, in which a yellow
      fluorescent protein was inserted, together with cyan fluorescent protein-tagged
      Gbetagamma subunits and appropriate receptors in HEK293 cells. Together with
      assays for receptor activation and receptor-G protein interaction, it is possible
      to characterize large parts of the G(S) signaling cascade. When A(2A)-adenosine
      or beta(1)-adrenergic receptors are coexpressed with G(S) in HEK293T cells, the
      receptor-G(S) interaction was on the same time scale as A(2A) receptor activation
      with a time constant of <50 ms. G(S) activation was markedly slower and around
      450 ms with similar kinetics following activation of A(2A)- or beta(1)-receptors.
      Taken together, our kinetic measurements demonstrate that the rate of G(S)
      activation limits initiation of G(S)-coupled receptor signaling.

PMID- 16963444
TI  - MNNG-induced cell death is controlled by interactions between PARP-1, poly(ADP
      ribose) glycohydrolase, and XRCC1.
AB  - PARP-1 (poly(ADP-ribose) polymerases) modifies proteins with poly(ADP-ribose),
      which is an important signal for genomic stability. ADP-ribose polymers also
      mediate cell death and are degraded by poly(ADP-ribose) glycohydrolase (PARG).
      Here we show that the catalytic domain of PARG interacts with the
      automodification domain of PARP-1. Furthermore, PARG can directly down-regulate
      PARP-1 activity. PARG also interacts with XRCC1, a DNA repair factor that is
      recruited by DNA damage-activated PARP-1. We investigated the role of XRCC1 in
      cell death after treatment with supralethal doses of the alkylating agent MNNG.
      Only in XRCC1-proficient cells MNNG induced a considerable accumulation of
      poly(ADP-ribose). Similarly, extracts of XRCC1-deficient cells produced large ADP
      ribose polymers if supplemented with XRCC1. Consequently, MNNG triggered in XRCC1
      proficient cells the translocation of the apoptosis inducing factor from
      mitochondria to the nucleus followed by caspase-independent cell death. In XRCC1
      deficient cells, the same MNNG treatment caused non-apoptotic cell death without
      accumulation of poly(ADP-ribose). Thus, XRCC1 seems to be involved in regulating
      a poly(ADP-ribose)-mediated apoptotic cell death.

PMID- 16963445
TI  - GATA-1-mediated transcriptional repression yields persistent transcription factor
      IIB-chromatin complexes.
AB  - The hematopoietic GATA factors GATA-1 and GATA-2, which have distinct and
      overlapping roles to regulate blood cell development, are reciprocally expressed
      during erythropoiesis. GATA-1 directly represses Gata2 transcription, and reduced
      GATA-2 synthesis promotes red blood cell development. Gata2 repression involves
      "GATA switches" in which GATA-1 displaces GATA-2 from Gata2 regulatory regions.
      We show that extragenic GATA switch sites occupied by GATA-2 associate with as
      much RNA polymerase II (Pol II) and basal transcription factors as present at the
      active Gata2 promoters. Pol II bound to GATA switch sites in the active locus was
      phosphorylated on serine 5 of the carboxyl-terminal domain, indicative of
      elongation competence. GATA-1-mediated displacement of GATA-2 from GATA switch
      sites reduced Pol II recruitment to all sites except the far upstream -77-kb
      region. Surprisingly, TFIIB occupancy persisted at most sites upon repression.
      These results indicate that GATA-2-bound extragenic regulatory elements recruit
      Pol II, GATA-1 binding expels Pol II, and despite the persistent TFIIB-chromatin
      complexes, Pol II recruitment is blocked.

PMID- 16963446
TI  - Structural basis for the differential regulation of DNA by the methionine
      repressor MetJ.
AB  - The Met regulon in Escherichia coli encodes several proteins responsible for the
      biosynthesis of methionine. Regulation of the expression of most of these
      proteins is governed by the methionine repressor protein MetJ and its co
      repressor, the methionine derivative S-adenosylmethionine. Genes controlled by
      MetJ contain from two to five sequential copies of a homologous 8-bp sequence
      called the metbox. A crystal structure for one of the complexes, the repressor
      tetramer bound to two metboxes, has been reported (Somers, W. S., and S. E.
      Phillips (1992) Nature 359, 387-393), but little structural work on the larger
      assemblies has been done presumably because of the difficulties in
      crystallization and the variability in the number and sequences of metboxes for
      the various genes. Small angle neutron scattering was used to study complexes of
      MetJ and S-adenosylmethionine with double-stranded DNA containing two, three, and
      five metboxes. Our results demonstrate that the crystal structure of the two
      metbox complex is not the native solution conformation of the complex. Instead,
      the system adopts a less compact conformation in which there is decreased
      interaction between the adjacent MetJ dimers. Models built of the higher order
      complexes from the scattering data show that the three-metbox complex is
      organized much like the two-metbox complex. However, the five-metbox complex
      differs significantly from the smaller complexes, providing much closer packing
      of the adjacent MetJ dimers and allowing additional contacts not available in the
      crystal structure. The results suggest that there is a structural basis for the
      differences observed in the regulatory effectiveness of MetJ for the various
      genes of the Met regulon.

PMID- 16963447
TI  - Identification and characterization of a novel gene, Mcpr1, and its possible
      function in the proliferation of embryonic palatal mesenchymal cells.
AB  - We cloned a novel mouse cDNA, Mcpr1 (mouse cleft palate-related gene 1), between
      retinoic acid (RA)-treated murine embryonic palatal and control shelves by
      improved subtractive hybridization. Its transcript was identified by Northern
      blotting. The open reading frame encodes 132 amino acids and shows almost no
      identity to other genetic products. Mcpr1 expression could be detected
      extensively in adult mouse tissues and during murine embryonic development. It
      was identified to be significantly stimulated by RA in murine palatal shelves at
      embryonic day 12 and in palatal mesenchymal cells in vitro. We demonstrate that
      MCPR1 protein was localized primarily in the cytoplasm and could be synthesized
      and secreted by transfected COS-7 cells. Both the secretory and recombinant
      proteins of Mcpr1 inhibited proliferation of murine embryonic palatal mesenchymal
      cells and impeded the progression from the G1 to S phase in the cell cycle. The
      cells were prone to apoptosis after exposure to glutathione S-transferase-MCPR1.
      Furthermore, knockdown of MCPR1 protein levels by antisense oligodeoxynucleotides
      promoted progression of cells from the G1 to S phase and completely abolished the
      RA-induced block of the cell cycle from the G1 to S phase. These findings suggest
      that Mcpr1 might function as one of the RA-up-regulated genes involved in
      inhibiting cell proliferation during palatogenesis and RA-induced cleft palate by
      regulating proliferation and apoptosis of embryonic palatal mesenchymal cells and
      might even play a role in the development of many other organs.

PMID- 16963448
TI  - Repeated phosphopeptide motifs in human Claspin are phosphorylated by Chk1 and
      mediate Claspin function.
AB  - Claspin is a checkpoint protein involved in ATR (ataxia telangiectasia mutated-
      and Rad3-related)-dependent Chk1 activation in Xenopus and human cells. In
      Xenopus, Claspin interacts with Chk1 after DNA damage through a region containing
      two highly conserved repeats, which becomes phosphorylated during the checkpoint
      response. Because this region is also conserved in human Claspin, we investigated
      the regulation and function of these potential phosphorylation sites in human
      Claspin. We found that Claspin is phosphorylated in vivo at Thr-916 in response
      to replication stress and UV damage. Mutation of these phosphorylation sites on
      Claspin inhibited Claspin-Chk1 interaction in vivo, impaired Chk1 activation, and
      induced premature chromatin condensation in cells, indicating a defect in
      replication checkpoint. In addition, we found that Thr-916 on Claspin is
      phosphorylated by Chk1, suggesting that Chk1 regulates Claspin during checkpoint
      response. These results together indicate that phosphorylation of Claspin repeats
      in human Claspin is important for Claspin function and the regulation of Claspin
      Chk1 interaction in human cells.

PMID- 16963449
TI  - Leptin transcriptionally enhances peptide transporter (hPepT1) expression and
      activity via the cAMP-response element-binding protein and Cdx2 transcription
      factors.
AB  - PepT1 is an intestinal epithelial apical membrane transporter that is expressed
      in the small intestine, with little or no expression in the normal colon.
      However, we previously demonstrated that colonic PepT1 may be expressed during
      chronic inflammation. To begin elucidating inflammatory hPepT1 signaling, we
      herein investigated the long term leptin treatments, on PepT1 expression and
      activity in Caco2-BBE cells, and began to reveal the involved signaling pathways.
      We successfully cloned the 723-bp hPepT1 promoter region and identified the human
      transcription initiation site 86 bp upstream from the translation start site.
      Leptin treatment dose- and time-dependently increased hPepT1 promoter and
      transport activities in Caco2-BBE cells, with maximal activity observed in cells
      treated with 100 nM leptin for 8 h. Under these conditions, we observed 2-fold
      increases in hPepT1 mRNA and protein expression, as well as increased transport
      activity. Our molecular analyses of possible signal-transduction pathways
      revealed that leptin treatment enhanced the intracellular levels of cAMP and
      phosphorylated cAMP-response element-binding protein (CREB) protein in Caco2-BBE
      cells, whereas our deletion, mutation, and CDX2 overexpression analyses
      demonstrated that interaction of the Cdx2 and phosphorylated CREB transcription
      factors was essential for leptin-induced hPepT1 transcription in Caco2-BBE cells.
      Our results indicate that leptin, which is increased in inflamed colonic mucosa,
      triggers colonic expression of hPepT1 via the CREB and Cdx2 transcription
      factors. These findings provide important new insights into the mechanisms of
      intestinal inflammation and may suggest new therapeutic modalities in the future.

PMID- 16963450
TI  - PEGylation and multimerization of the anti-p185HER-2 single chain Fv fragment
      4D5: effects on tumor targeting.
AB  - A major goal in antibody design for cancer therapy is to tailor the
      pharmacokinetic properties of the molecule according to specific treatment
      requirements. Key parameters determining the pharmacokinetics of therapeutic
      antibodies are target specificity, affinity, stability, and size. Using the
      p185HER-2 (HER-2)-specific scFv 4D5 as model system, we analyzed how changes in
      molecular weight and valency independently affect antigen binding and tumor
      localization. By employing multimerization and PEGylation, four different
      antibody formats were generated and compared with the scFv 4D5. First, dimeric
      and tetrameric miniantibodies were constructed by fusion of self-associating,
      disulfide-linked peptides to the scFv 4D5. Second, we attached a 20-kDa PEG
      moiety to the monovalent scFv and to the divalent miniantibody at the respective
      C terminus. In all formats, serum stability and full binding reactivity of the
      scFv 4D5 were retained. Functional affinity, however, did change. An avidity
      increase was achieved by multimerization, whereas PEGylation resulted in a 5-fold
      decreased affinity. Nevertheless, the PEGylated monomer showed an 8.5-fold, and
      the PEGylated dimer even a 14.5-fold higher tumor accumulation than the
      corresponding scFv, 48 h post-injection, because of a significantly longer serum
      half-life. In comparison, the non-PEGylated bivalent and tetravalent
      miniantibodies showed only a moderate increase in tumor localization compared
      with the scFv, which correlated with the degree of multimerization. However,
      these non-PEGylated formats resulted in higher tumor-to-blood ratios. Both
      multimerization and PEGylation represent thus useful strategies to tailor the
      pharmacokinetic properties of therapeutic antibodies and their combined use can
      additively improve tumor targeting.

PMID- 16963451
TI  - Characterization of novel splice variants of LGR7 and LGR8 reveals that receptor
      signaling is mediated by their unique low density lipoprotein class A modules.
AB  - The relaxin and insulin-like peptide 3 receptors, LGR7 and LGR8, respectively,
      are unique members of the leucine-rich repeat-containing G-protein-coupled
      receptor (LGR) family, because they possess an N-terminal motif with homology to
      the low density lipoprotein class A (LDLa) modules. By characterizing several
      LGR7 and LGR8 splice variants, we have revealed that the LDLa module directs
      ligand-activated cAMP signaling. The LGR8-short variant encodes an LGR8 receptor
      lacking the LDLa module, whereas LGR7-truncate, LGR7-truncate-2, and LGR7
      truncate-3 all encode truncated secreted proteins retaining the LGR7 LDLa module.
      LGR8-short and an engineered LGR7 variant missing its LDLa module, LGR7-short,
      bound to their respective ligands with high affinity but lost their ability to
      signal via stimulation of intracellular cAMP accumulation. Conversely, secreted
      LGR7-truncate protein with the LDLa module was able to block relaxin-induced LGR7
      cAMP signaling and did so without compromising the ability of LGR7 to bind to
      relaxin or be expressed on the cell membrane. Although the LDLa module of LGR7
      was N-glycosylated at position Asn-14, an LGR7 N14Q mutant retained relaxin
      binding affinity and cAMP signaling, implying that glycosylation is not essential
      for optimal LDLa function. Using real-time PCR, the expression of mouse LGR7
      truncate was detected to be high in, and specific to, the uterus of pregnant
      mice. The differential expression and evolutionary conservation of LGR7-truncate
      further suggests that it may also play an important role in vivo. This study
      highlights the essential role of the LDLa module in LGR7 and LGR8 function and
      introduces a novel model of GPCR regulation.

PMID- 16963452
TI  - Selection and characterization of Her2 binding-designed ankyrin repeat proteins.
AB  - Designed ankyrin repeat proteins (DARPins) are a novel class of binding proteins
      that bind their target protein with high affinity and specificity and have very
      favorable expression and stability properties. We describe here the in vitro
      selection of DARPins against human epidermal growth factor receptor 2 (Her2), an
      important target for cancer therapy and diagnosis. Several DARPins bind to the
      same epitope as trastuzumab (Herceptin), but none were selected that bind to the
      epitope of pertuzumab (Omnitarg). Some of the selected DARPins bind with low
      nanomolar affinity (Kd=7.3 nm) to the target. Further analysis revealed that all
      DARPins are highly specific and do not cross-react with epidermal growth factor
      receptor I (EGFR1) or any other investigated protein. The selected DARPins
      specifically bind to strongly Her2-overexpressing cell lines such as SKBR-3 but
      also recognize small amounts of Her2 on weakly expressing cell lines such as MCF
      7. Furthermore, the DARPins also lead to a highly specific and strong staining of
      plasma membranes of paraffinated sections of human mamma-carcinoma tissue. Thus,
      the selected DARPins might be used for the development of diagnostic tests for
      the status of Her2 overexpression in different adenocarcinomas, and they may be
      further evaluated for their potential in targeted therapy since their favorable
      expression properties make the construction of fusion proteins very convenient.

PMID- 16963453
TI  - Nitric oxide produced in response to engagement of beta2 integrins on human
      neutrophils activates the monomeric GTPases Rap1 and Rap2 and promotes adhesion.
AB  - We found that engagement of beta2 integrins on human neutrophils increased the
      levels of GTP-bound Rap1 and Rap2. Also, the activation of Rap1 was blocked by
      PP1, SU6656, LY294002, GF109203X, or BAPTA-AM, which indicates that the
      downstream signaling events in Rap1 activation involve Src tyrosine kinases,
      phosphoinositide 3-kinase, protein kinase C, and release of calcium.
      Surprisingly, the beta2 integrin-induced activation of Rap2 was not regulated by
      any of the signaling pathways mentioned above. However, we identified nitric
      oxide as the signaling molecule involved in beta2 integrin-induced activation of
      Rap1 and Rap2. This was illustrated by the fact that engagement of beta2
      integrins increased the production of nitrite, a stable end-product of nitric
      oxide. Furthermore, pretreatment of neutrophils with Nomega-monomethyl-L
      arginine, or 1400W, which are inhibitors of inducible nitric-oxide synthase,
      blocked beta2 integrin-induced activation of Rap1 and Rap2. Similarly, Rp-8pCPT
      cGMPS, an inhibitor of cGMP-dependent serine/threonine kinases, also blunted the
      beta2 integrin-induced activation of Rap GTPases. Also nitric oxide production
      and its downstream activation of cGMP-dependent serine/threonine kinases were
      essential for proper neutrophil adhesion by beta2 integrins. Thus, we made the
      novel findings that beta2 integrin engagement on human neutrophils triggers
      production of nitric oxide and its downstream signaling is essential for
      activation of Rap GTPases and neutrophil adhesion.

PMID- 16963454
TI  - Transactivation of sphingosine 1-phosphate receptors is essential for vascular
      barrier regulation. Novel role for hyaluronan and CD44 receptor family.
AB  - The role for hyaluronan (HA) and CD44 in vascular barrier regulation is unknown.
      We examined high and low molecular weight HA (HMW-HA, approximately 1,000 kDa;
      LMW-HA, approximately 2.5 kDa) effects on human transendothelial monolayer
      electrical resistance (TER). HMW-HA increased TER, whereas LMW-HA induced
      biphasic TER changes ultimately resulting in EC barrier disruption. HMW-HA
      induced the association of the CD44s isoform with, and AKT-mediated
      phosphorylation of, the barrier-promoting sphingosine 1-phosphate receptor (S1P1)
      within caveolin-enriched lipid raft microdomains, whereas LMW-HA induced brief
      CD44s association with S1P1 followed by sustained association of the CD44v10
      isoform with, and Src and ROCK 1/2-mediated phosphorylation of, the barrier
      disrupting S1P3 receptor. HA-induced EC cytoskeletal reorganization and TER
      alterations were abolished by either disruption of lipid raft formation, CD44
      blocking antibody or siRNA-mediated reductions in expression of CD44 isoforms.
      Silencing S1P1, AKT1, or Rac1 blocked the barrier enhancing effects of HA whereas
      silencing S1P3, Src, ROCK1/2, or RhoA blocked the barrier disruption induced by
      LMW-HA. In summary, HA regulates EC barrier function through novel differential
      CD44 isoform interaction with S1P receptors, S1P receptor transactivation, and
      RhoA/Rac1 signaling to the EC cytoskeleton.

PMID- 16963455
TI  - Yin Yang 1 physically interacts with Hoxa11 and represses Hoxa11-dependent
      transcription.
AB  - Yin Yang 1 (YY1) plays an indispensable role in embryonic development. YY1
      contains an evolutionarily conserved, 22-amino acid segment, the PHO homology
      region (PHR), which is located within its central domain (spacer) and has been
      shown previously to participate in the recruitment of Polycomb group of proteins
      and in YY1-mediated transcription. In this report, we show that the PHR
      physically interacts with several Abd-B-type Hox proteins. Although ectopic
      expression of Hoxa11 enhanced target promoter activity, overexpression of YY1
      repressed this effect, which was abrogated by YY1 siRNA and the histone
      deacetylase inhibitor trichostatin A. We have further demonstrated that this
      suppression effect was the result of YY1-dependent recruitment of HDAC2 to the
      Hoxa11 target promoter. Taken together, our findings show that YY1 represses
      Hoxa11-dependent transcription via interactions with the Hox proteins and HDAC
      recruitment, providing a link between an Abd-type Hox protein and a Polycomb
      group protein at the level of direct protein-protein interactions. These findings
      not only provide a novel insight into YY1 function but also identify a new
      regulation of homeotic protein-mediated transcriptional regulation in general.

PMID- 16963456
TI  - Functional categorization of the conserved basic amino acid residues in TrmH
      (tRNA (Gm18) methyltransferase) enzymes.
AB  - Transfer RNA (Gm18) methyltransferase (TrmH) catalyzes the methyl transfer from S
      adenosyl-L-methionine (AdoMet) to the 2'-OH group of the G18 ribose in tRNA. To
      identify amino acid residues responsible for the tRNA recognition, we have
      carried out the alanine substitution mutagenesis of the basic amino acid residues
      that are conserved only in TrmH enzymes and not in the other SpoU proteins. We
      analyzed the mutant proteins by S-adenosyl-L-homocysteine affinity column
      chromatography, gel mobility shift assay, and kinetic assay of the methyl
      transfer reaction. Based on these biochemical studies and the crystal structure
      of TrmH, we found that the conserved residues can be categorized according to
      their role (i) in the catalytic center (Arg-41), (ii) in the initial site of tRNA
      binding (Lys-90, Arg-166, Arg-168, and Arg-176), (iii) in the tRNA binding site
      required for continuation the catalytic cycle (Arg-8, Arg-19, and Lys-32), (iv)
      in the structural element involved in release of S-adenosyl-L-homocysteine (Arg
      11-His-71-Met-147 interaction), (v) in the assisted phosphate binding site (His
      34), or (vi) in an unknown function (Arg-109). Furthermore, the difference
      between the Kd and Km values for tRNA suggests that the affinity for tRNA is
      enhanced in the presence of AdoMet. To confirm this idea, we carried out the
      kinetic studies, a gel mobility shift assay with a mutant protein disrupted in
      the catalytic center, and the analytical gel-filtration chromatography. Our
      experimental results clearly show that the enzyme has a semi-ordered sequential
      mechanism in which AdoMet both enhances the affinity for tRNA and induces
      formation of the tetramer structure.

PMID- 16963457
TI  - The crystal and solution structures of glyceraldehyde-3-phosphate dehydrogenase
      reveal different quaternary structures.
AB  - The presence of an isoform of glyceraldehyde-3-phosphate dehydrogenase
      (kmGAPDH1p) associated with the cell wall of a flocculent strain of Kluyveromyces
      marxianus was the first report of a non-cytosolic localization of a glycolytic
      enzyme, but the mechanism by which the protein is transported to the cell surface
      is not known. To identify structural features that could account for the multiple
      localizations of the protein, the three-dimensional structure of kmGAPDH1p was
      determined by x-ray crystallography and small angle x-ray scattering. The x-ray
      crystallographic structure of kmGAPDH1p revealed a dimer, although all GAPDH
      homologs studied thus far have a tetrameric structure with 222 symmetry.
      Interestingly, the structure of kmGAPDH1p in solution revealed a tetramer with a
      70 degrees tilt angle between the dimers. Moreover, the separation between the
      centers of the dimers composing the kmGAPDH1p tetramer diminished from 34 to 30 A
      upon NAD(+) binding, this latter value being similar to the observed in the
      crystallographic models of GAPDH homologs. The less compact structure of apo
      kmGAPDH1p could already be the first image of the transition intermediate between
      the tetramer observed in solution and the dimeric form found in the crystal
      structure, which we postulate to exist in vivo because of the protein's multiple
      subcellular localizations in this yeast species.

PMID- 16963458
TI  - Human pancreatitis-associated protein forms fibrillar aggregates with a native
      like conformation.
AB  - Human pancreatitis-associated protein was identified in pathognomonic lesions of
      Alzheimer disease, a disease characterized by the presence of filamentous protein
      aggregates. Here, we showed that at physiological pH, human pancreatitis
      associated protein forms non-Congo Red-binding, proteinase K-resistant fibrillar
      aggregates with diameters from 6 up to as large as 68 nm. Interestingly, circular
      dichroism and Fourier transform infrared spectra showed that, unlike typical
      amyloid fibrils, which have a cross-beta-sheet structure, these aggregates have a
      very similar secondary structure to that of the native protein, which is composed
      of two alpha-helices and eight beta-strands, as determined by NMR techniques.
      Surface structure analysis showed that the positively charged and negatively
      charged residues were clustered on opposite sides, and strong electrostatic
      interactions between molecules were therefore very likely, which was confirmed by
      cross-linking experiments. In addition, several hydrophobic residues were found
      to constitute a continuous hydrophobic surface. These results and protein
      aggregation prediction using the TANGO algorithm led us to synthesize peptide
      Thr(84) to Ser(116), which, very interestingly, was found to form amyloid-like
      fibrils with a cross-beta structure. Thus, our data suggested that human
      pancreatitis-associated protein fibrillization is initiated by protein
      aggregation primarily because of electrostatic interactions, and the loop from
      residues 84 to 116 may play an important role in the formation of fibrillar
      aggregates with a native-like conformation.

PMID- 16963459
TI  - Effect of efflux pump inhibitors on bile resistance and in vivo colonization of
      Campylobacter jejuni.
AB  - OBJECTIVES: The multidrug efflux pump CmeABC is essential for Campylobacter
      colonization in animal intestine by mediating bile resistance. The objective of
      this study is to examine the effect of inhibition of the CmeABC pump by efflux
      pump inhibitor (EPI) on the susceptibility of Campylobacter to bile salts and to
      evaluate the in vivo efficacy of two EPIs on the colonization of Campylobacter in
      a host. METHODS: Two wild-type Campylobacter jejuni strains and their isogenic
      cmeB mutants were used to determine the susceptibilities of the strains to
      various bile salts in the presence of EPI MC-207,110 or MC-04,124. The in vivo
      effect of the EPIs on the colonization of C. jejuni in a host was evaluated using
      a chicken model system. RESULTS: The presence of EPIs resulted in a 16- to 512
      fold reduction in the MICs of bile salts in both C. jejuni strains. Compared with
      wild-type strains, cmeB mutants displayed much smaller magnitudes of reduction in
      the MICs of bile salts, indicating that the in vitro effect of the EPI is
      primarily mediated by the CmeABC efflux pump. Investigation of 21 Campylobacter
      isolates from various origins further showed that the EPI MC-207,110 decreased
      bile resistance in all isolates. Single oral administration of EPI (MC-207,110 or
      MC-04,124) at two different doses reduced colonization of C. jejuni in chickens
      at 2-4 days post-inoculation only. Oral administration of MC-207,110 for three
      consecutive days following inoculation of C. jejuni did not result in a more
      significant reduction in the level of Campylobacter colonization in chickens.
      CONCLUSIONS: Inhibition of Campylobacter efflux pumps by EPIs is a potential
      means for therapeutic intervention to reduce colonization of C. jejuni in humans
      and animal reservoirs.

PMID- 16963460
TI  - Free radical production and quenching in honeys with wound healing potential.
AB  - OBJECTIVES: Honey-impregnated wound dressings are now available on drug tariff in
      the UK, though the modes of action of honeys with antibacterial and wound healing
      properties are not entirely clear. The action of some but not all of these honeys
      is linked to the production of hydrogen peroxide on dilution of the honey with
      wound exudate. The present study investigates both free radical production and
      the antioxidant potential of some honeys, properties which may have a role to
      play in wound healing. METHODS: Free radical production and quenching of three
      honey types (manuka, antibacterial but non-peroxide-producing; pasture,
      antibacterial peroxide-producing; commercial heat processed, non-antibacterial)
      was investigated by electron paramagnetic resonance (EPR) spectroscopy; quenching
      was also examined using a superoxide quenching assay. RESULTS: All honeys tested
      had antioxidant potential, with manuka able to completely quench added radicals
      within 5 min of spiking. Only the peroxide-producing honey (pasture PS9) was
      found to form radicals on dilution. CONCLUSIONS: The ability to modulate
      production and quenching of free radicals may contribute to the demonstrated
      ability of some honeys to help in resolving the state of inflammation typifying
      chronic wounds.

PMID- 16963461
TI  - WHO Health Promotion Glossary: new terms.
AB  - The WHO Health Promotion Glossary was written to facilitate understanding,
      communication and cooperation among those engaged in health promotion at the
      local, regional, national and global levels. Two editions of the Glossary have
      been released, the first in 1986 and the second in 1998, and continued revision
      of the document is necessary to promote consensus regarding meanings and to take
      account of developments in thinking and practice. In this update 10 new terms
      that are to be included in the Glossary are presented. Criteria for the inclusion
      of terms in the Glossary are that they differentiate health promotion from other
      health concepts, or have a specific application or meaning when used in relation
      to health promotion. The terms defined here are: burden of disease; capacity
      building; evidence-based health promotion; global health; health impact
      assessment; needs assessment; self-efficacy; social marketing; sustainable health
      promotion strategies, and; wellness. WHO will continue to periodically update the
      Health Promotion Glossary to ensure its relevance to the international health
      promotion community.

PMID- 16963462
TI  - Rene Dubos and Jared Diamond dream of Dutch polders.

PMID- 16963463
TI  - World Championship 2006 in Germany: sponsorship through Coca Cola, McDonald's,
      Anheuser-Busch.

PMID- 16963464
TI  - Statistical methods in genetics.
AB  - In recent years, a very large variety of statistical methodologies, at various
      levels of complexity, have been put forward to analyse genotype data and detect
      genetic variations that may be responsible for increasing the susceptibility to
      disease. This review provides a concise account of a number of selected
      statistical methods for population-based association mapping, from single-marker
      tests of association to multi-marker data mining techniques for gene-gene
      interaction detection.

PMID- 16963465
TI  - Chara myosin and the energy of cytoplasmic streaming.
AB  - Recently, it was found that myosin generating very fast cytoplasmic streaming in
      Chara corallina has very high ATPase activity. To estimate the energy consumed by
      this myosin, its concentration in the internodal cells of C. corallina was
      determined by quantitative immunoblot. It was found that the concentration of
      Chara myosin was considerably high (200 nM) and the amount of ATP consumed by
      this myosin would exceed that supplied by dark respiration if all myosin
      molecules were fully activated by the interaction with actin. These results and
      model calculations suggested that the energy required to generate cytoplasmic
      streaming is very small and only one-hundredth of the existing myosin is enough
      to maintain the force for the streaming in the Chara cell.

PMID- 16963466
TI  - External quality assurance of HER2 fluorescence in situ hybridisation testing:
      results of a UK NEQAS pilot scheme.
AB  - BACKGROUND AND AIMS: Trastuzumab provides clinical benefit for advanced and early
      breast cancer patients whose tumours over-express or have gene amplification of
      the HER2 oncogene. The UK National External Quality Assessment Scheme (NEQAS) for
      immunohistochemical testing was established to assess and improve the quality of
      HER2 immunohistochemical testing. However, until recently, no provision was
      available for HER2 fluorescence in situ hybridisation (FISH) testing. A pilot
      scheme was set up to review the performance of FISH testing in clinical
      diagnostic laboratories. METHODS: FISH was performed in 6 reference and 31
      participating laboratories using a cell line panel with known HER2 status.
      RESULTS: Using results from reference laboratories as a criterion for acceptable
      performance, 60% of all results returned by participants were appropriate and 78%
      either appropriate or acceptable. However, 22.4% of results returned were deemed
      inappropriate, including 13 cases (4.2%) where a misdiagnosis would have been
      made had these been clinical specimens. CONCLUSIONS: The results of three
      consecutive runs show that both reference laboratories and a proportion of
      routine clinical diagnostic (about 25%) centres can consistently achieve
      acceptable quality control of HER2 testing. Data from a significant proportion of
      participating laboratories show that further steps are required, including those
      taken via review of performance under schemes such as NEQAS, to improve quality
      of HER2 testing by FISH in the "real world".

PMID- 16963468
TI  - 5' and 3' region variability in the dopamine transporter gene (SLC6A3), pesticide
      exposure and Parkinson's disease risk: a hypothesis-generating study.
AB  - The dopamine transporter gene (SLC6A3) is a candidate gene for Parkinson's
      disease (PD) on the basis of its critical role in dopaminergic neurotransmission.
      Previously, we identified 22 SNPs in the 5' region of SLC6A3, which segregate as
      eight haplotypes that differ in transcriptional activity when transfected in rat
      dopamine-producing cells. In the present work from a case-control study size of
      293 cases and 395 controls, we employed a cladistic approach to examine gene
      disease association. First, we found strong evidence of balancing selection in
      this region, as determined by a Tajima's D statistic of 2.97 (P<0.001). Second,
      we found that the eight haplotypes fit into two main clades and that diplotypes
      of these clades were marginally associated with PD. Then, after we classified
      cases and controls by the number of risk alleles, accounting for the well-known
      3' region VNTR polymorphism, we found that having two or more risk alleles
      resulted in a modest but significant increase in PD risk [odds ratio=1.58; 95%
      confidence interval (CI): 1.03-2.40]. Finally, we detected a significant
      interaction between occupational pesticide exposure in men and the number of risk
      alleles. Among pesticide-exposed subjects, the odds ratio for having two or more
      risk alleles was 5.66 (95% CI: 1.73-18.53). Thus, allelic variants in SLC6A3,
      which affect gene expression, are associated with PD in this population and may
      interact with occupational pesticide exposure to increase PD risk.

PMID- 16963467
TI  - My approach to reporting a gastric biopsy.
AB  - The protracted inflammation of the gastric mucosa induces profound changes in the
      microenvironment of the gastric cells. These changes modify the molecular signals
      that orchestrate morphogenesis and cell differentiation in the stem cells of the
      crypts. The expression of this adjustment to the new microenvironment is
      evidenced by the appearance of differentiated metaplastic cells (intestinal,
      bronchial-ciliated, pancreatic or (pseudo) pyloric, all deriving from the same
      embryological origin). The inability of stem cells to readapt to the new
      microenvironment may lead to genomic aberrations such as the retention of
      cellular products (glassy cells) or to neoplastic transformation. In this report,
      parameters such as gastric mucosal inflammation, Helicobacter pylori, atrophy,
      intestinal metaplasia and/or pseudopyloric metaplasia found in gastric biopsy
      specimens were individually classified according to their extension in sections
      as grade 1 (focal distribution in sections from individual biopsy specimens) and
      grade 2 (present in the entire width-distance across-in sections from individual
      biopsy specimen). The rationale is that a biopsy grade 2 was harvested from a
      larger mucosal area having that particular change. Each individual parameter
      gives a score, and the sum of all individual scores gives the total score. The
      proposed system might allow monitoring the results of treatment in follow-up
      biopsies. Divergent clinical results in the frequency/incidence of gastritis
      (including body-autoimmune gastritis), of H pylori strains, of various
      metaplasias and neoplasias, in disparate geographical regions substantiate the
      conviction that these parameters are much influenced by the environment. This
      knowledge is crucial, considering that environmental diseases are theoretically
      preventable.

PMID- 16963469
TI  - Depletion of type IA regulatory subunit (RIalpha) of protein kinase A (PKA) in
      mammalian cells and tissues activates mTOR and causes autophagic deficiency.
AB  - The human PRKAR1A gene encodes the regulatory subunit 1-alpha (RIalpha) of the
      cAMP-dependent protein kinase A (PKA) holoenzyme. Regulation of the catalytic
      activity of PKA is the only well-studied function of RIalpha. Inactivating
      PRKAR1A mutations cause primary pigmented nodular adrenocortical disease (PPNAD)
      or Carney complex (CNC), an inherited syndrome associated with abnormal skin
      pigmentation and multiple neoplasias, including PPNAD. Histochemistry of tissues
      from CNC patients is indicative of autophagic deficiency and this led us to
      investigate the relationship between RIalpha and mammalian autophagy. We found
      that fluorescently tagged RIalpha associates with late endosomes and
      autophagosomes in cultured cells. The number of autophagosomes in prkar1a-/-
      mouse embryonic fibroblasts (MEFs) was reduced compared with wild-type MEFs.
      RIalpha co-immunoprecipitated with mTOR kinase, a major regulator of autophagy.
      Phosphorylated-mTOR levels and mTOR activity were dramatically increased in
      prkar1a-/- mouse cells, and in HEK 293 cells with RIalpha levels reduced by
      siRNA. Finally, phosphorylated-mTOR levels and mTOR activity were increased in
      CNC cells and in PPNAD tissues. These data suggest that RIalpha deficiency
      decreases autophagy by the activation of mTOR, providing a molecular basis to
      autophagic deficiency in PPNAD.

PMID- 16963470
TI  - A large mediastinal tumour?

PMID- 16963471
TI  - Renin angiotensin blockade in heart failure with preserved ejection fraction: The
      signal gets stronger.

PMID- 16963472
TI  - The perindopril in elderly people with chronic heart failure (PEP-CHF) study.
AB  - AIMS: Many patients who receive a diagnosis of heart failure have neither a low
      left ventricular (LV) ejection fraction nor valve disease. Few substantial
      randomized controlled trials have been conducted in this population, none has
      focussed on patients with evidence of diastolic dysfunction and none has shown
      clear benefit on symptoms, morbidity, or mortality. METHODS AND RESULTS: This was
      a randomized double-blind trial, comparing placebo with perindopril, 4 mg/day in
      patients aged > or =70 years with a diagnosis of heart failure, treated with
      diuretics and an echocardiogram suggesting diastolic dysfunction and excluding
      substantial LV systolic dysfunction or valve disease. The primary endpoint was a
      composite of all-cause mortality and unplanned heart failure related
      hospitalization with a minimum follow-up of 1 year. A total of 850 patients were
      randomized. Their mean age was 76 (SD 5) years and 55% were women. Median follow
      up was 2.1 (IQR 1.5-2.8) years. Enrollment and event rates were lower than
      anticipated, reducing the power of the study to show a difference in the primary
      endpoint to 35%. Many patients withdrew from perindopril (28%) and placebo (26%)
      after 1 year and started taking open-label ACE-inhibitors. Overall, 107 patients
      assigned to placebo and 100 assigned to perindopril reached the primary endpoint
      (HR 0.919: 95% CI 0.700-1.208; P = 0.545). By 1 year, reductions in the primary
      outcome (HR 0.692: 95% CI 0.474-1.010; P = 0.055) and hospitalization for heart
      failure (HR 0.628: 95% CI 0.408-0.966; P = 0.033) were observed and functional
      class (P < 0.030) and 6-min corridor walk distance (P = 0.011) had improved in
      those assigned to perindopril. CONCLUSION: Uncertainty remains about the effects
      of perindopril on long-term morbidity and mortality in this clinical setting
      since this study had insufficient power for its primary endpoint. However,
      improved symptoms and exercise capacity and fewer hospitalizations for heart
      failure in the first year were observed on perindopril, during which most
      patients were on assigned therapy, suggesting that it may be of benefit in this
      patient population.

PMID- 16963473
TI  - Young people and sexual health: whose rights? Whose responsibilities? R. (on the
      application of Axon) v. Secretary of State for Health & another.

PMID- 16963474
TI  - Combined use of plasmapheresis and antidigoxin antibodies in a patient with
      severe digoxin intoxication and acute renal failure.

PMID- 16963475
TI  - Dogmas and surprises about the renin-angiotensin system and sodium reabsorption.

PMID- 16963476
TI  - Bilateral renal aneurysms in a chronic hepatitis B patient.

PMID- 16963477
TI  - Phenotype and genotype: perspectives for peritoneal dialysis patients.

PMID- 16963478
TI  - Mental health at the third month of haemodialysis as a predictor of short-term
      survival.
AB  - BACKGROUND: The aim of this study was to evaluate the survival of patients
      initiating haemodialysis (HD), and to analyse whether low health-related quality
      of life (HRQoL) levels are predictors of mortality in the short-term, controlling
      certain variables that had been shown in other studies to have a bearing on
      survival, and using scores, standardized for age and sex, of the HRQoL
      measurement tool employed. METHODS: This is a multicentric prospective study of
      all patients on HD in all the dialysis units in Asturias, a region with a little
      over one million inhabitants, from 1 January 2001 to 30 September 2002. A total
      of 199 patients initiated HD in our region and survived the first 3 months. Of
      these, 137 patients who remained on HD for at least 3 months had complete
      responses on HRQoL measures. RESULTS: It was observed that adjusted relative risk
      (RR) of death increased by 5% for each year of age increase (RR=1.05, 95% CI 1.01
      1.09: P=0.006); in the same way, for each increase in the Mental Component
      Summary (MCS) score, the adjusted RR of death diminished by 4% (RR=0.96, 95% CI
      0.94-0.99; P=0.006). CONCLUSION: Mental health has been shown to be a factor
      independently associated with mortality; as the MCS score worsens the adjusted RR
      of death of a patient on HD increases.

PMID- 16963479
TI  - High prevalence of febrile urinary tract infections after paediatric renal
      transplantation.
AB  - BACKGROUND: Adult data suggest that urinary tract infections occur frequently
      after renal transplantation (RTx) and contribute to mortality and graft loss;
      data in children are limited. Therefore, we evaluated prevalence, short and long
      term morbidity and confounding factors of febrile UTI (fUTI) after paediatric
      RTx. METHODS: In a retrospective cross-sectional study of three centres, we
      analysed data on 110 children followed for 4.9+/-3.4 years after successful
      transplantation. RESULTS: 40/110 (36%) patients had at least one fUTI at a median
      time of 0.98 years (range 0.02-8.96) after RTx; 11 patients (28%) had recurrent
      fUTI. Serum creatinine (SCr) rose significantly from 1.15+/-1.13 to 1.83+/-1.69
      mg/dl, (P<0.001) during the fUTI, declining to baseline values after treatment.
      At the last followed-up calculated mean, GFR was comparable between fUTI and non
      fUTI groups (75+/-26 vs 71+/-22 ml/min/1.73 m2). During fUTI mean, C-reactive
      protein (CRP) increased to 123+/-75 mg/l. Febrile UTI were significantly more
      frequent in girls compared to boys (22/44 vs 18/66, P<0.05) but occurred
      significantly earlier in boys than in girls [median 0.63 (range 0.02-4.15) vs
      1.07 (0.04-8.96) years after RTx; P<0.02]. Also, patients with urinary tract
      malformations (UTMs) and neurogenic bladder as underlying diagnosis and those
      with urological surgery prior to transplantation had an increased risk for fUTI.
      CONCLUSION: fUTI is a frequent complication with significant short-term morbidity
      especially in girls and children with UTMs, neurogenic bladder and those with
      urological surgery. Long-term follow-up and prospective studies confirming
      specific risk factors, preventive measures and impact on graft survival are
      necessary.

PMID- 16963480
TI  - Circulating antibodies to nephrin in patients with type 1 diabetes.
AB  - BACKGROUND: Patients with type 1 diabetes typically develop autoantibodies to
      antigens of the pancreatic islet cells including insulin, glutamic acid
      decarboxylase and the protein tyrosine phosphatase-related islet antigen 2
      protein. Nephrin is a protein shared by the kidney glomeruli, pancreatic beta
      cells and islet microendothelia. Since circulating antibodies to nephrin have
      been shown to cause proteinuria, we wanted to test whether such autoantibodies
      can be detected in diabetic patients. METHODS: We developed a
      radioimmunoprecipitation assay and analysed samples in a follow-up series of 66
      patients with type 1 diabetes. RESULTS: A total of 24% of the patients tested
      positive for nephrin autoantibodies at diagnosis, whereas 23, 14 and 18% had
      these antibodies at 2, 5 and 10 years, respectively. During the follow-up at 16
      19 years after diagnosis, 14 patients had signs of renal injury and 29% of them
      tested positive for nephrin autoantibodies in at least one sample. CONCLUSIONS:
      We conclude that a subset of patients with type 1 diabetes present with
      circulating autoantibodies to nephrin. However, the present data do not allow
      conclusions of a causative role for these antibodies in the pathogenesis of
      proteinuria in diabetes.

PMID- 16963481
TI  - Uric acid and the immune response.

PMID- 16963482
TI  - Clinical and molecular cytogenetic characterisation of a newly recognised
      microdeletion syndrome involving 2p15-16.1.
AB  - BACKGROUND: During whole genome microarray-based comparative genomic
      hybridisation (array CGH) screening of subjects with idiopathic intellectual
      disability, we identified two unrelated individuals with a similar de novo
      interstitial microdeletion at 2p15-2p16.1. Both individuals share a similar
      clinical phenotype including moderate to severe intellectual disability,
      autism/autistic features, microcephaly, structural brain anomalies including
      cortical dysplasia/pachygyria, renal anomalies (multicystic kidney,
      hydronephrosis), digital camptodactyly, visual impairment, strabismus, neuromotor
      deficits, communication and attention impairments, and a distinctive pattern of
      craniofacial features. Dysmorphic craniofacial features include progressive
      microcephaly, flat occiput, widened inner canthal distance, small palpebral
      fissures, ptosis, long and straight eyelashes, broad and high nasal root
      extending to a widened, prominent nasal tip with elongated, smooth philtrum,
      rounding of the upper vermillion border and everted lower lips. METHODS: Clinical
      assessments, and cytogenetic, array CGH and fluorescence in situ hybridisation
      (FISH) analyses were performed. RESULTS: The microdeletions discovered in each
      individual measured 4.5 Mb and 5.7 Mb, spanning the chromosome 2p region from
      57.2 to 61.7 Mb and from 56 to 61.7 Mb, respectively. Each deleted clone in this
      range demonstrated a dosage reduction from two to one copy in each proband except
      for clone RP11-79K21, which was present in three copies in each proband and in
      four copies in their respective parents (two per each chromosome 2 homologue).
      DISCUSSION: The common constellation of features found in the two affected
      subjects indicates that they have a newly recognised microdeletion syndrome
      involving haploinsufficiency of one or more genes deleted within at least a 4.5
      Mb segment of the 2p15-16.1 region.

PMID- 16963484
TI  - The centromeric 11p15 imprinting centre is also involved in Silver-Russell
      syndrome.
AB  - Silver-Russell syndrome (SRS) is a heterogeneous disorder characterised by severe
      intrauterine and postnatal growth retardation, limb and body asymmetry, a typical
      facial appearance and less common dysmorphisms. Recently, epimutations and
      maternal duplications affecting the short arm of chromosome 11 have been shown to
      have a crucial role in the aetiology of the disease. Disturbances in the same
      genomic region cause the overgrowth disorder Beckwith-Wiedemann syndrome (BWS).
      In BWS, mutations in the telomeric as well as in the centromeric imprinting
      centres (ICR1 and ICR2) in 11p15 can be observed. In SRS, methylation defects in
      the imprinted region in 11p15 were considered to be restricted to the telomeric
      ICR1. They can be detected in about 30% of patients. This article reports on the
      first patient with SRS with a cryptic duplication restricted to the centromeric
      ICR2 domain in 11p15. The maternally inherited duplication in this patient
      included a region of 0.76-1 Mbp and affected the genes regulated by the ICR2,
      among them CDKN1C and LIT1. This study provides evidence for a role for this
      imprinting centre in the aetiology of SRS and shows that SRS presents a picture
      genetically opposite to that of BWS.

PMID- 16963483
TI  - Development of a genotyping microarray for Usher syndrome.
AB  - BACKGROUND: Usher syndrome, a combination of retinitis pigmentosa (RP) and
      sensorineural hearing loss with or without vestibular dysfunction, displays a
      high degree of clinical and genetic heterogeneity. Three clinical subtypes can be
      distinguished, based on the age of onset and severity of the hearing impairment,
      and the presence or absence of vestibular abnormalities. Thus far, eight genes
      have been implicated in the syndrome, together comprising 347 protein-coding
      exons. METHODS: To improve DNA diagnostics for patients with Usher syndrome, we
      developed a genotyping microarray based on the arrayed primer extension (APEX)
      method. Allele-specific oligonucleotides corresponding to all 298 Usher syndrome
      associated sequence variants known to date, 76 of which are novel, were arrayed.
      RESULTS: Approximately half of these variants were validated using original
      patient DNAs, which yielded an accuracy of >98%. The efficiency of the Usher
      genotyping microarray was tested using DNAs from 370 unrelated European and
      American patients with Usher syndrome. Sequence variants were identified in
      64/140 (46%) patients with Usher syndrome type I, 45/189 (24%) patients with
      Usher syndrome type II, 6/21 (29%) patients with Usher syndrome type III and 6/20
      (30%) patients with atypical Usher syndrome. The chip also identified two novel
      sequence variants, c.400C>T (p.R134X) in PCDH15 and c.1606T>C (p.C536S) in USH2A.
      CONCLUSION: The Usher genotyping microarray is a versatile and affordable
      screening tool for Usher syndrome. Its efficiency will improve with the addition
      of novel sequence variants with minimal extra costs, making it a very useful
      first-pass screening tool.

PMID- 16963485
TI  - A retrospective study of New Zealand case law involving assisted reproduction
      technology and the social recognition of 'new' family.
AB  - The New Zealand Human Assisted Reproductive Technology (HART) Act became law in
      2004. In this article, we provide a retrospective analysis of New Zealand case
      law from September 1990 to March 2004, leading up to the creation of the HART
      Act. We examine the new understandings of parenting (developed through the
      routine use of ART in New Zealand) which the case law attempted to test. We
      examine these concepts against the previous understandings of family enshrined in
      the pre-existing legislation, which formed the basis for judicial rulings in the
      various cases to which we refer. In conclusion, we provide a brief summary of the
      2004 HART legislation and draw comparisons between the old and new legislative
      and bureaucratic frameworks that define and support New Zealand family structure.
      We suggest that a change in cultural backdrop is occurring from the traditional
      western ideology of the nuclear family towards the traditional Maori concept of
      family formation, which includes a well-accepted traditional practice of
      guardianship and a more open and extended family structure. This 'new' structure
      reflects the contemporary lived experience of family kinship in western societies
      as individualized and open to choice.

PMID- 16963486
TI  - Pharmacokinetics and metabolism in mice of IDN 5390 (13-(N-Boc-3-i
      butylisoserinoyl)-C-7,8-seco-10-deacetylbaccatin III), a new oral c-seco-taxane
      derivative with antiangiogenic property effective on paclitaxel-resistant tumors.
AB  - IDN 5390 (13-(N-Boc-3-i-butylisoserinoyl)-C-7,8-seco-10-deacetylbaccatin III) is
      a new taxane, derived from 7,8-C-seco-10-deacetylbaccatin, selected for its
      ability to inhibit angiogenesis, mainly by acting on endothelial cell motility,
      and for its selective activity on class III beta-tubulin. In vivo, IDN 5390 shows
      activity against paclitaxel-sensitive and -resistant tumors when administered on
      a prolonged, continuous dosage schedule. We studied the pharmacokinetics and
      bioavailabilty of the drug in mice after single and repeated oral treatment. IDN
      5390 was rapidly absorbed after oral administration, with good bioavailability
      (43%). After intravenous injection, it was extensively distributed in tissue,
      mainly the liver, kidney, and heart, with low but persistent levels in brain. The
      kinetics appear dose-dependent with a clearance of 2.6, 1.4, and 0.9 l/kg at,
      respectively, 60, 90, and 120 mg/kg, and a half-life 24, 36, and 54 min. After
      prolonged daily oral doses given for 2 weeks, we found that there was a decrease
      in drug availability; i.e., the area under the concentration-time curve value
      after p.o. daily administration on day 14 was 2-fold lower than that on day 1.
      Metabolism plays a major role in elimination of the drug, and at least 12
      metabolites were identified in feces and urine. The percentage excreted as
      metabolites after an oral dose (42%) was higher than that after the i.v. dose
      (33%), suggesting a first-pass effect. Four metabolites were found in plasma at
      detectable levels; one of them, with restored taxane scaffold, is a species 3
      times more potent than IDN 5390, possibly contributing to the observed anti-tumor
      activity.

PMID- 16963487
TI  - Comparison of coumarin-induced toxicity between sandwich-cultured primary rat
      hepatocytes and rats in vivo: a toxicogenomics approach.
AB  - Sandwich-cultured primary rat hepatocytes are often used as an in vitro model in
      toxicology and pharmacology. However, loss of liver-specific functions, in
      particular, the decline of cytochrome P450 (P450) enzyme activity, limits the
      value of this model for prediction of in vivo toxicity. In this study, we
      investigated whether a hepatic in vitro system with improved metabolic competence
      enhances the predictability for coumarin-induced in vivo toxicity by using a
      toxicogenomics approach. Therefore, primary rat hepatocytes were cultured in
      sandwich configuration in medium containing a mixture of low concentrations of
      P450 inducers, phenobarbital, dexamethasone, and beta-naphthoflavone. The
      toxicogenomics approach used enabled comparison of similar mechanistic end-points
      at the molecular level between in vitro and in vivo conditions, namely, compound
      induced changes in multiple genes and signaling pathways. Toxicant-induced
      cytotoxic effects and gene expression profiles observed in hepatocytes cultured
      in modified medium and hepatocytes cultured in standard medium (without inducers)
      were compared with results from a rat in vivo study. Coumarin was used as a model
      compound because its toxicity depends on bioactivation by P450 enzymes.
      Metabolism of coumarin toward active metabolites, coumarin-induced cytotoxicity,
      and gene expression modulation were more pronounced in hepatocytes cultured in
      modified medium compared with hepatocytes cultured in standard medium. In
      addition, more genes and biological pathways were similarly affected by coumarin
      in hepatocytes cultured in modified medium and in vivo. In conclusion, these
      experiments showed that for coumarin-induced toxicity, sandwich-cultured
      hepatocytes maintained in modified medium better represent the situation in vivo
      compared with hepatocytes cultured in standard medium.

PMID- 16963488
TI  - In vivo metabolism of L-methionine in mice: evidence for stereoselective
      formation of methionine-d-sulfoxide and quantitation of other major metabolites.
AB  - Flavin-containing monooxygenases (FMOs) 1-4 oxidize methionine (Met) to
      methionine sulfoxide (MetO). FMO3, the primary isoform expressed in adult human
      liver, has the lowest Km and favors methionine-d-sulfoxide (Met-d-O) formation
      over methionine-l-sulfoxide. Because female mice, but not males, also express
      FMO3 in liver, levels of Met and its major metabolites were determined in male or
      female mice dosed with 400 mg/kg Met i.p. The results show that Met levels in
      male and female mouse liver or plasma increased significantly at both 15 and 30
      min after the Met treatment; Met plasma and liver levels at 30 min were similar
      to or lower than the corresponding levels at 15 min. Liver and plasma MetO levels
      increased significantly in both sexes at 30 min, and Met-d-O was the major MetO
      diastereomer detected. Interestingly, less than 0.1% of the Met dose was excreted
      in the urine (0-24 h) as Met and Met-d-O. S-Adenosylmethionine (SAM) was the
      major metabolite detected in liver at 15 min. Liver SAM levels at 30 min were
      lower than the levels at 15 min, and the plasma SAM levels at both 15 and 30 min
      were much lower than the corresponding levels in the liver. Increases in liver
      and/or plasma S-adenosyl-l-homocysteine, 5'-deoxy-5'-(methylthio)adenosine, and N
      acetyl-l-methionine were also detected. Taken together, these results suggest
      that mice extensively and rapidly used the Met dose. Although mice exhibited
      increases in tissue MetO levels, a major role for FMO3 in Met-d-O formation is
      not certain since the MetO increases were mostly similar in both males and
      females.

PMID- 16963489
TI  - CYP2C9 inhibition: impact of probe selection and pharmacogenetics on in vitro
      inhibition profiles.
AB  - Drug-drug interactions may cause serious adverse events in the clinical setting,
      and the cytochromes P450 are the enzyme system most often implicated in these
      interactions. Cytochrome P450 2C is the second most abundant subfamily of
      cytochrome P450 enzymes and is responsible for metabolism of almost 20% of
      currently marketed drugs. The most abundant isoform of this subfamily is CYP2C9,
      which is the major clearance pathway for the low therapeutic index drugs warfarin
      and phenytoin. Considering the importance of CYP2C9 to drug-drug interactions,
      the in vitro-in vivo extrapolation of drug-drug interactions for CYP2C9 may be
      confounded by the presence of polymorphic variants and the possibility of
      multiple binding regions within the CYP2C9 active site, leading to the potential
      for genotype- and substrate-dependent inhibition. To address the issues of
      genotype-dependent enzyme inhibition as well as probe substrate correlations, the
      inhibitory potency (Ki) of 28 effector molecules was assessed with five commonly
      used probes of CYP2C9 in both the CYP2C9.1 and CYP2C9.3 proteins. The inhibition
      of CYP2C9.1 and CYP2C9.3 by the battery of inhibitors with five substrate probes
      demonstrated differential inhibition potency not only between the two genotypes
      but also across substrate probes. Furthermore, the substrate probes fell into
      three distinct classes depending on genotype, suggesting that multiple probes may
      be needed to fully assess inhibition of CYP2C9 in vitro. Thus, both genotype and
      choice of probe substrate must be considered when attempting to predict potential
      CYP2C9 drug-drug interactions from in vitro data.

PMID- 16963490
TI  - Rhythm control and cardioversion.

PMID- 16963491
TI  - A specific loop in human DNA polymerase mu allows switching between creative and
      DNA-instructed synthesis.
AB  - Human DNA polymerase mu (Polmu) is a family X member that has terminal
      transferase activity but, in spite of a non-orthodox selection of the template
      information, displays its maximal catalytic efficiency in DNA-templated
      reactions. As terminal deoxynucleotidyl transferase (TdT), Polmu has a specific
      loop (loop1) that could provide this enzyme with its terminal transferase
      activity. When loop1 was deleted, human Polmu lacked TdT activity but improved
      DNA-binding and DNA template-dependent polymerization. Interestingly, when loop1
      from TdT was inserted in Polmu (substituting its cognate loop1), the resulting
      chimaera displayed TdT activity, preferentially inserting dGTP residues, but had
      a strongly reduced template-dependent polymerization activity. Therefore, a
      specialized loop in Polmu, that could adopt alternative conformations, appears to
      provide this enzyme with a dual capacity: (i) template independency to create new
      DNA information, in which loop1 would have an active role by acting as a
      'pseudotemplate'; (ii) template-dependent polymerization, in which loop1 must
      allow binding of the template strand. Recent in vivo and in vitro data suggest
      that such a dual capacity could be advantageous to resolve microhomology-mediated
      end-joining reactions.

PMID- 16963492
TI  - Site-specific labeling of supercoiled DNA.
AB  - Visualization of site-specific labels in long linear or circular DNA allows
      unambiguous identification of various local DNA structures. Here we describe a
      novel and efficient approach to site-specific DNA labeling. The restriction
      enzyme SfiI binds to DNA but leaves it intact in the presence of calcium and
      therefore may serve as a protein label of 13 bp recognition sites. Since SfiI
      requires simultaneous interaction with two DNA recognition sites for stable
      binding, this requirement is satisfied by providing an isolated recognition site
      in the DNA target and an additional short DNA duplex also containing the
      recognition site. The SfiI/DNA complexes were visualized with AFM and the
      specificity of the labeling was confirmed by the length measurements. Using this
      approach, two sites in plasmid DNA were labeled in the presence of a large excess
      of the helper duplex to compete with the formation of looped structures of the
      intramolecular synaptic complex. We show that the labeling procedure does not
      interfere with the superhelical tension-driven formation of alternative DNA
      structures such as cruciforms. The complex is relatively stable at low and high
      pH (pH 5 and 9) making the developed approach attractive for use at conditions
      requiring the pH change.

PMID- 16963493
TI  - A scalable method for multiplex LED-controlled synthesis of DNA in capillaries.
AB  - As research in synthetic biology and genomic sciences becomes more widespread,
      the need for diverse oligonucleotide populations has increased. To limit reagent
      cost, it would be advantageous to obtain high quality populations in minute
      amounts. Towards that end, synthesis of DNA strands in capillaries utilizing
      photolabile 3-nitrophenylpropyloxycarbonyl (NPPOC) chemistry and ultraviolet
      light emitting diodes (UV-LEDs) was examined. Multiple oligonucleotides were made
      in single capillaries and were characterized by hybridization, sequencing and
      gene synthesis. DNA synthesized in capillaries was capable of being hybridized
      and signal intensities correlated with microarray data. Sequencing demonstrated
      that the oligonucleotides were of high quality (up to 44% perfect sequences).
      Oligonucleotides were combined and used successfully for gene synthesis. This
      system offers a novel, scalable method to synthesize high quality
      oligonucleotides for biological applications.

PMID- 16963495
TI  - Sequence-specific recognition of colicin E5, a tRNA-targeting ribonuclease.
AB  - Colicin E5 is a novel Escherichia coli ribonuclease that specifically cleaves the
      anticodons of tRNA(Tyr), tRNA(His), tRNA(Asn) and tRNA(Asp). Since this activity
      is confined to its 115 amino acid long C-terminal domain (CRD), the recognition
      mechanism of E5-CRD is of great interest. The four tRNA substrates share the
      unique sequence UQU within their anticodon loops, and are cleaved between Q
      (modified base of G) and 3' U. Synthetic minihelix RNAs corresponding to the
      substrate tRNAs were completely susceptible to E5-CRD and were cleaved in the
      same manner as the authentic tRNAs. The specificity determinant for E5-CRD was
      YGUN at -1 to +3 of the 'anticodon'. The YGU is absolutely required and the
      extent of susceptibility of minihelices depends on N (third letter of the
      anticodon) in the order A > C > G > U accounting for the order of susceptibility
      tRNA(Tyr) > tRNA(Asp) > tRNA(His), tRNA(Asn). Contrastingly, we showed that GpUp
      is the minimal substrate strictly retaining specificity to E5-CRD. The effect of
      contiguous nucleotides is inconsistent between the loop and linear RNAs,
      suggesting that nucleotide extension on each side of GpUp introduces a structural
      constraint, which is reduced by a specific loop structure formation that includes
      a 5' pyrimidine and 3' A.

PMID- 16963494
TI  - The Drosophila G9a gene encodes a multi-catalytic histone methyltransferase
      required for normal development.
AB  - Mammalian G9a is a histone H3 Lys-9 (H3-K9) methyltransferase localized in
      euchromatin and acts as a co-regulator for specific transcription factors. G9a is
      required for proper development in mammals as g9a-/g9a- mice show growth
      retardation and early lethality. Here we describe the cloning, the biochemical
      and genetical analyses of the Drosophila homolog dG9a. We show that dG9a shares
      the structural organization of mammalian G9a, and that it is a multi-catalytic
      histone methyltransferase with specificity not only for lysines 9 and 27 on H3
      but also for H4. Surprisingly, it is not the H4-K20 residue that is the target
      for this methylation. Spatiotemporal expression analyses reveal that dG9a is
      abundantly expressed in the gonads of both sexes, with no detectable expression
      in gonadectomized adults. In addition we find a low but clearly observable level
      of dG9a transcript in developing embryos, larvae and pupae. Genetic and RNAi
      experiments reveal that dG9a is involved in ecdysone regulatory pathways.

PMID- 16963496
TI  - NOP132 is required for proper nucleolus localization of DEAD-box RNA helicase
      DDX47.
AB  - Previously, we described a novel nucleolar protein, NOP132, which interacts with
      the small GTP binding protein RRAG A. To elucidate the function of NOP132 in the
      nucleolus, we identified proteins that interact with NOP132 using mass
      spectrometric methods. NOP132 associated mainly with proteins involved in
      ribosome biogenesis and RNA metabolism, including the DEAD-box RNA helicase
      protein, DDX47, whose yeast homolog is Rrp3, which has roles in pre-rRNA
      processing. Immunoprecipitation of FLAG-tagged DDX47 co-precipitated rRNA
      precursors, as well as a number of proteins that are probably involved in
      ribosome biogenesis, implying that DDX47 plays a role in pre-rRNA processing.
      Introduction of NOP132 small interfering RNAs induced a ring-like localization of
      DDX47 in the nucleolus, suggesting that NOP132 is required for the appropriate
      localization of DDX47 within the nucleolus. We propose that NOP132 functions in
      the recruitment of pre-rRNA processing proteins, including DDX47, to the region
      where rRNA is transcribed within the nucleolus.

PMID- 16963497
TI  - Codon usage bias and tRNA over-expression in Buchnera aphidicola after aromatic
      amino acid nutritional stress on its host Acyrthosiphon pisum.
AB  - Codon usage bias and relative abundances of tRNA isoacceptors were analysed in
      the obligate intracellular symbiotic bacterium, Buchnera aphidicola from the
      aphid Acyrthosiphon pisum, using a dedicated 35mer oligonucleotide microarray.
      Buchnera is archetypal of organisms living with minimal metabolic requirements
      and presents a reduced genome with high-evolutionary rate. Codonusage in Buchnera
      has been overcome by the high mutational bias towards AT bases. However, several
      lines of evidence for codon usage selection are given here. A significant
      correlation was found between tRNA relative abundances and codon composition of
      Buchnera genes. A significant codon usage bias was found for the choice of rare
      codons in Buchnera: C-ending codons are preferred in highly expressed genes,
      whereas G-ending codons are avoided. This bias is not explained by GC skew in the
      bacteria and might correspond to a selection for perfect matching between codon
      anticodon pairs for some essential amino acids in Buchnera proteins. Nutritional
      stress applied to the aphid host induced a significant overexpression of most of
      the tRNA isoacceptors in bacteria. Although, molecular regulation of the tRNA
      operons in Buchnera was not investigated, a correlation between relative
      expression levels and organization in transcription unit was found in the genome
      of Buchnera.

PMID- 16963499
TI  - Characterization of DGCR8/Pasha, the essential cofactor for Drosha in primary
      miRNA processing.
AB  - DGCR8/Pasha is an essential cofactor for Drosha, a nuclear RNase III that cleaves
      the local hairpin structures embedded in long primary microRNA transcripts (pri
      miRNAs) in eukaryotes. Although our knowledge of pri-miRNA processing has
      significantly advanced in recent years, the precise role of DGCR8 in this pathway
      remains unclear. In our present study, we dissect the domains in DGCR8 that
      contribute to the processing of pri-miRNAs and the subcellular localization of
      DGCR8. Drosha is stabilized through an interaction between its middle domain and
      the conserved C-terminal domain of DGCR8. Furthermore, DGCR8, but not Drosha, can
      directly and stably interact with pri-miRNAs, and the tandem dsRNA-binding
      domains (dsRBDs) in DGCR8 are responsible for this recognition. Moreover, the
      DGCR8 N-terminal region upstream of its dsRBDs is unnecessary for pri-miRNA
      processing but is critical for nuclear localization. Our study thus provides
      further insights into the mechanism of action of the Drosha-DGCR8 complex in pri
      miRNA processing.

PMID- 16963500
TI  - Olfactory Coding in Antennal Neurons of the Malaria Mosquito, Anopheles gambiae.
AB  - Olfactory receptor neurons (ORNs) in the antenna of insects serve to encode odors
      in action potential activity conducted to the olfactory lobe of the
      deuterocerebrum. We performed an analysis of the electrophysiological responses
      of olfactory neurons in the antennae of the female malaria mosquito Anopheles
      gambiae s.s. and investigated the effect of blood feeding on responsiveness.
      Forty-four chemicals that are known to be present in human volatile emanations
      were used as odor stimuli. We identified 6 functional types of trichoid sensilla
      and 5 functional types of grooved-peg sensilla (GP) based on a hierarchical
      cluster analysis. Generalist ORNs, tuned to a broad range of odors, moderate
      specialist ORNs and 2 ORNs tuned to only one odor were identified in different
      sensilla types. Neurons in GP were tuned to more polar compounds including the
      important behavioral attractant ammonia and its synergist L-lactic acid,
      responses to which were found only in GP. Combinatorial coding is the most
      plausible principle operating in the olfactory system of this mosquito species.
      We document for the first time both up- and downregulation of ORN responsiveness
      after blood feeding. Modulation of host-seeking and oviposition behavior is
      associated with both qualitative and quantitative changes in the peripheral
      sensory system.

PMID- 16963498
TI  - Aberrant 3' splice sites in human disease genes: mutation pattern, nucleotide
      structure and comparison of computational tools that predict their utilization.
AB  - The frequency distribution of mutation-induced aberrant 3' splice sites (3'ss) in
      exons and introns is more complex than for 5' splice sites, largely owing to
      sequence constraints upstream of intron/exon boundaries. As a result, prediction
      of their localization remains a challenging task. Here, nucleotide sequences of
      previously reported 218 aberrant 3'ss activated by disease-causing mutations in
      131 human genes were compared with their authentic counterparts using currently
      available splice site prediction tools. Each tested algorithm distinguished
      authentic 3'ss from cryptic sites more effectively than from de novo sites. The
      best discrimination between aberrant and authentic 3'ss was achieved by the
      maximum entropy model. Almost one half of aberrant 3'ss was activated by AG
      creating mutations and approximately 95% of the newly created AGs were selected
      in vivo. The overall nucleotide structure upstream of aberrant 3'ss was
      characterized by higher purine content than for authentic sites, particularly in
      position -3, that may be compensated by more stringent requirements for positive
      and negative nucleotide signatures centred around position -11. A newly developed
      online database of aberrant 3'ss will facilitate identification of splicing
      mutations in a gene or phenotype of interest and future optimization of splice
      site prediction tools.

PMID- 16963501
TI  - Mirror writing: neurological reflections on an unusual phenomenon.
AB  - Mirror writing is an unusual script, in which the writing runs in the opposite
      direction to normal, with individual letters reversed, so that it is most easily
      read using a mirror. This writing is seen in healthy individuals; it is also
      associated with various focal lesions that most commonly involve the left
      hemisphere, as well as with certain diffuse cerebral disorders. Mirror writing is
      nearly always undertaken with the left hand, and left-handers, and those whose
      languages are written leftwards, have an unusual facility for this writing.
      Concerning possible underlying processes, the implications of using the left hand
      when writing are considered first. Motor pathways that may be important, the
      surrogate model of bimanual mirror movements and the contribution of the corpus
      callosum are then discussed. The reasons why left-handed writing is mirrored, and
      the factors that tend to inhibit mirroring, are outlined. After commenting on
      mirrored motor and visual engrams, the possibility that the right hemisphere may
      play an important part is entertained, and Leonardo da Vinci's unique, habitual
      mirror writing proves to be of unexpected relevance. Further investigations,
      ranging from epidemiological to functional imaging studies, may provide valuable
      insights into mirror writing.

PMID- 16963502
TI  - Sugar binding and protein conformational changes in lactose permease.
AB  - Lactose permease is an integral membrane protein that uses the cell membrane's
      proton gradient for import of lactose. Based on extensive biochemical data and a
      substrate-bound crystal structure, intermediates involved in lactose/H(+) co
      transport have been suggested. Yet, the transport mechanism, especially the
      coupling of protonation states of essential residues and protein conformational
      changes involved in the transport, is not understood. Here we report molecular
      dynamics simulations of membrane-embedded lactose permease in different
      protonation states, both in the presence and in the absence of lactose. The
      results analyzed in terms of pore diameter, salt-bridge formation, and substrate
      motion, strongly implicate Glu(269) as one of the main proton translocation
      sites, whose protonation state controls several key steps of the transport
      process. A critical ion pair (Glu(269) and Arg(144)) was found to keep the
      cytoplasmic entrance open, but via a different mechanism than the currently
      accepted model. After protonation of Glu(269), the salt bridge between Glu(269)
      and Arg(144) was found to break, and Arg(144) to move away from Glu(269),
      establishing a new salt bridge with Glu(126); furthermore, neutralization of
      Glu(269) and the displacement of Arg(144) and consequently of water molecules
      from the interdomain region was seen to initiate the closing of the cytoplasmic
      half channel (2.6-4.0 A reduction in diameter in the cytoplasmic constriction
      region in 10 ns) by allowing hydrophobic surfaces of the N- and C-domains to
      fuse. Charged Glu(269) was found to strongly bind the lactose permeant,
      indicating that proton transfer from water or another residue to Glu(269) is a
      prerequisite for unbinding of lactose from the binding pocket.

PMID- 16963503
TI  - Effect of charge substitutions at residue his-142 on voltage gating of connexin43
      channels.
AB  - Previous studies indicate that the carboxyl terminal of connexin43 (Cx43CT) is
      involved in fast transjunctional voltage gating. Separate studies support the
      notion of an intramolecular association between Cx43CT and a region of the
      cytoplasmic loop (amino acids 119-144; referred to as "L2"). Structural analysis
      of L2 shows two alpha-helical domains, each with a histidine residue in its
      sequence (H126 and H142). Here, we determined the effect of H142 replacement by
      lysine, alanine, and glutamate on the voltage gating of Cx43 channels. Mutation
      H142E led to a significant reduction in the frequency of occurrence of the
      residual state and a prolongation of dwell open time. Macroscopically, there was
      a large reduction in the fast component of voltage gating. These results
      resembled those observed for a mutant lacking the carboxyl terminal (CT) domain.
      NMR experiments showed that mutation H142E significantly decreased the Cx43CT-L2
      interaction and disrupted the secondary structure of L2. Overall, our data
      support the hypothesis that fast voltage gating involves an intramolecular
      particle-receptor interaction between CT and L2. Some of the structural
      constrains of fast voltage gating may be shared with those involved in the
      chemical gating of Cx43.

PMID- 16963504
TI  - Disease-causing mutations in proteins: structural analysis of the CYP1B1
      mutations causing primary congenital glaucoma in humans.
AB  - In this communication, we report an in-depth structure-based analysis of the
      human CYP1b1 protein carrying disease-causing mutations that are discovered in
      patients suffering from primary congenital glaucoma (PCG). The "wild-type" and
      the PCG mutant structures of the human CYP1b1 protein obtained from comparative
      modeling were subjected to long molecular dynamics simulations with an intention
      of studying the possible impact of these mutations on the protein structure and
      hence its function. Analysis of time evolution as well as time averaged values of
      various structural properties--especially of those of the functionally important
      regions: the heme binding region, substrate binding region, and substrate access
      channel--gave some insights into the possible structural characteristics of the
      disease mutant and the wild-type forms of the protein. In a nutshell, compared to
      the wild-type the core regions in the mutant structures are associated with
      subtle but significant changes, and the functionally important regions seem to
      adopt such structures that are not conducive for the wild-type-like
      functionality.

PMID- 16963505
TI  - TASSER-Lite: an automated tool for protein comparative modeling.
AB  - This study involves the development of a rapid comparative modeling tool for
      homologous sequences by extension of the TASSER methodology, developed for
      tertiary structure prediction. This comparative modeling procedure was validated
      on a representative benchmark set of proteins in the Protein Data Bank composed
      of 901 single domain proteins (41-200 residues) having sequence identities
      between 35-90% with respect to the template. Using a Monte Carlo search scheme
      with the length of runs optimized for weakly/nonhomologous proteins, TASSER often
      provides appreciable improvement in structure quality over the initial template.
      However, on average, this requires approximately 29 h of CPU time per sequence.
      Since homologous proteins are unlikely to require the extent of conformational
      search as weakly/nonhomologous proteins, TASSER's parameters were optimized to
      reduce the required CPU time to approximately 17 min, while retaining TASSER's
      ability to improve structure quality. Using this optimized TASSER (TASSER-Lite),
      we find an average improvement in the aligned region of approximately 10% in root
      mean-square deviation from native over the initial template. Comparison of TASSER
      Lite with the widely used comparative modeling tool MODELLER showed that TASSER
      Lite yields final models that are closer to the native. TASSER-Lite is provided
      on the web at
      (http://cssb.biology.gatech.edu/skolnick/webservice/tasserlite/index.html).

PMID- 16963506
TI  - Quantitative analysis of the role of receptor recycling in T cell polarization.
AB  - Activation of T cells of the immune system involves recognition of the antigen by
      the T cell receptor and subsequent internalization and recycling of this
      receptor. We present a numerical model for this process that accounts for the
      polarity of the intracellular traffic determined by the polarization of the
      microtubule-organizing center to the immunological synapse. Unexpectedly, the
      model explains the observed accumulation of receptors at the immunological
      synapse mainly as dynamic maintenance of the receptor density there, while the
      surface receptors everywhere else are depleted, even though the internalization
      occurs primarily at the synapse. In the case of an unsuccessful polarization of
      the microtubule-organizing center, which alters the polarity of the receptor
      trafficking, the model explains the absence of receptor accumulation as a dynamic
      downregulation at the synapse. The experiment shows that in this case the
      interaction of the T cell with its target is aborted. Disruption of recycling
      leads in the experiment to accumulation of the incompletely polarized cells. We
      propose that receptor recycling is a mechanism whereby the cell can sense its
      internal structure and detect polarity errors, analogous to checkpoint signaling
      mechanisms that ensure fidelity of cell division.

PMID- 16963507
TI  - Bio-microrheology: a frontier in microrheology.
AB  - Cells continuously adapt to changing conditions through coordinated molecular and
      mechanical responses. This adaptation requires the transport of molecules and
      signaling through intracellular regions with differing material properties, such
      as variations in viscosity or elasticity. To determine the impact of regional
      variations on cell structure and physiology, an approach, termed bio
      microrheology, or the study of deformation and flow of biological materials at
      small length scales has emerged. By tracking the thermal and driven motion of
      probe particles, organelles, or molecules, the local physical environment in
      distinct subcellular regions can be explored. On the surface or inside cells,
      tracking the motion of particles can reveal the rheological properties that
      influence cell features, such as shape and metastatic potential. Cellular
      microrheology promises to improve our concepts of regional and integrated
      properties, structures, and transport in live cells. Since bio-microrheology is
      an evolving methodology, many specific details, such as how to interpret complex
      combinations of thermally mediated and directed probe transport, remain to be
      fully explained. This work reviews the current state of the field and discusses
      the utility and challenges of this emerging approach.

PMID- 16963508
TI  - Switching sides: the actin/membrane lipid connection.

PMID- 16963509
TI  - Actin polymerization serves as a membrane domain switch in model lipid bilayers.
AB  - The ability of cells to mount localized responses to external or internal stimuli
      is critically dependent on organization of lipids and proteins in the plasma
      membrane. Involvement of the actin cytoskeleton in membrane organization has been
      documented, but an active role for actin networks that directly links internal
      organization of the cytoskeleton with membrane organization has not yet been
      identified. Here we show that branched actin networks formed on model lipid
      membranes enriched with the lipid second messenger PIP(2) trigger both temporal
      and spatial rearrangement of membrane components. Using giant unilamellar
      vesicles able to separate into two coexisting liquid phases, we demonstrate that
      polymerization of dendritic actin networks on the membrane induces phase
      separation of initially homogenous vesicles. This switch-like behavior depends
      only on the PIP(2)-N-WASP link between the membrane and actin network, and we
      find that the presence of a preexisting actin network spatially biases the
      location of phase separation. These results show that dynamic, membrane-bound
      actin networks alone can control when and where membrane domains form and may
      actively contribute to membrane organization during cell signaling.

PMID- 16963510
TI  - Statistical thermodynamics and kinetics of DNA multiplex hybridization reactions.
AB  - A general analytical description of the equilibrium and reaction kinetics of DNA
      multiplex hybridization has been developed. In this approach, multiplex
      hybridization is considered to be a competitive multichannel reaction process: a
      system wherein many species can react both specifically and nonspecifically with
      one another. General equations are presented that can consider equilibrium and
      kinetic models of multiplex hybridization systems comprised, in principle, of any
      number of targets and probes. Numerical solutions to these systems for both
      equilibrium and kinetic behaviors are provided. Practical examples demonstrate
      clear differences between results obtained from more common simplex methods, in
      which individual hybridization reactions are considered to occur in isolation;
      and multiplex hybridization, where desired and competitive cross-hybrid reactions
      between all possible pairs of strands are considered. In addition, sensitivities
      of the hybridization process of the perfect match duplex, to temperature, target
      concentration, and existence of sequence homology with other strands, are
      examined. This general approach also considers explicit sequence-dependent
      interactions between targets and probes involved in the reactions. Sequence
      dependent stabilities of all perfect match and mismatch duplex complexes are
      explicitly considered and effects of relative stability of cross-hybrid complexes
      are also explored. Results reveal several interdependent factors that strongly
      influence DNA multiplex hybridization behavior. These include: relative
      concentrations of all probes and targets; relative thermodynamic stability of all
      perfect match and mismatch complexes; sensitivity to temperature, particularly
      for mismatches; and amount of sequence homology shared by the probe and target
      strands in the multiplex mix.

PMID- 16963511
TI  - Flexible light-chain and helical structure of F-actin explain the movement and
      step size of myosin-VI.
AB  - Myosin-VI is a dimeric isoform of unconventional myosins. Single molecule
      experiments indicate that myosin-VI and myosin-V are processive molecular motors,
      but travel toward opposite ends of filamentous actin. Structural studies show
      several differences between myosin-V and VI, including a significant difference
      in the light-chain domain connecting the motor domains. Combining the measured
      kinetics of myosin-VI with the elasticity of the light chains, and the helical
      structure of F-actin, we compare and contrast the motility of myosin-VI with
      myosin-V. We show that the elastic properties of the light-chain domain control
      the stepping behavior of these motors. Simple models incorporating the motor
      elastic energy can quantitatively capture most of the observed data. Implications
      of our result for other processive motors are discussed.

PMID- 16963512
TI  - DNA as a metrology standard for length and force measurements with optical
      tweezers.
AB  - Optical tweezers have broad applications in studies of structures and processes
      in molecular and cellular biophysics. Use of optical tweezers for quantitative
      molecular-scale measurement requires careful calibration in physical units. Here
      we show that DNA molecules may be used as metrology standards for force and
      length measurements. Analysis of DNA molecules of two specific lengths allows
      simultaneous determination of all essential measurement parameters. We validate
      this biological-calibration method experimentally and with simulated data, and
      show that precisions in determining length scale factor ( approximately 0.2%),
      length offset ( approximately 0.03%), force scale factor ( approximately 2%), and
      compliance of the traps ( approximately 3%) are limited only by current
      measurement variation, much of which arises from polydispersity of the
      microspheres ( approximately 2%). We find this procedure to be simpler and more
      convenient than previous methods, and suggest that it provides an easily
      replicated standard that can insure uniformity of measurements made in different
      laboratories.

PMID- 16963513
TI  - Dynamics of single DNA looping and cleavage by Sau3AI and effect of tension
      applied to the DNA.
AB  - Looping and cleavage of single DNA molecules by the two-site restriction
      endonuclease Sau3AI were measured with optical tweezers. A DNA template
      containing many recognition sites was used, permitting loop sizes from
      approximately 10 to 10,000 basepairs. At high enzyme concentration, cleavage
      events were detected within 5 s and nearly all molecules were cleaved within 5
      min. Activity decreased approximately 10-fold as the DNA tension was increased
      from 0.03 to 0.7 pN. Substituting Ca(2+) for Mg(2+) blocked cleavage, permitting
      measurement of stable loops. At low tension, the initial rates of cleavage and
      looping were similar (approximately 0.025 s(-1) at 0.1 pN), suggesting that
      looping is rate limiting. Short loops formed more rapidly than long loops. The
      optimum size decreased from approximately 250 to 45 basepairs and the average
      number of loops (in 1 min) from 4.2 to 0.75 as tension was increased from 0.03 to
      0.7 pN. No looping was detected at 5 pN. These findings are in qualitative
      agreement with recent theoretical predictions considering only DNA mechanics, but
      we observed weaker suppression with tension and smaller loop sizes. Our results
      suggest that the span and elasticity of the protein complex, nesting of loops,
      and protein-induced DNA bending and wrapping play an important role.

PMID- 16963514
TI  - Torsional rigidities of weakly strained DNAs.
AB  - Measurements on unstrained linear and weakly strained large (> or =340 bp)
      circular DNAs yield torsional rigidities in the range C = 170-230 fJ fm. However,
      larger values, in the range C = 270-420 fJ fm, are typically obtained from
      measurements on sufficiently small (< or =247 bp) circular DNAs, and values in
      the range C = 300-450 fJ fm are obtained from experiments on linear DNAs under
      tension. A new method is proposed to estimate torsional rigidities of weakly
      supercoiled circular DNAs. Monte Carlo simulations of the supercoiling free
      energies of solution DNAs, and also of the structures of surface-confined
      supercoiled plasmids, were performed using different trial values of C. The
      results are compared with experimental measurements of the twist energy
      parameter, E(T), that governs the supercoiling free energy, and also with atomic
      force microscopy images of surface-confined plasmids. The results clearly
      demonstrate that C-values in the range 170-230 fJ fm are compatible with
      experimental observations, whereas values in the range C > or = 269 fJ fm, are
      incompatible with those same measurements. These results strongly suggest that
      the secondary structure of DNA is altered by either sufficient coherent bending
      strain or sufficient tension so as to enhance its torsional rigidity.

PMID- 16963515
TI  - The ToxCast program for prioritizing toxicity testing of environmental chemicals.
AB  - The U.S. Environmental Protection Agency (EPA) is developing methods for
      utilizing computational chemistry, high-throughput screening (HTS), and various
      toxicogenomic technologies to predict potential for toxicity and prioritize
      limited testing resources toward chemicals that likely represent the greatest
      hazard to human health and the environment. This chemical prioritization research
      program, entitled "ToxCast," is being initiated with the purpose of developing
      the ability to forecast toxicity based on bioactivity profiling. The proof-of
      concept phase of ToxCast will focus upon chemicals with an existing, rich
      toxicological database in order to provide an interpretive context for the
      ToxCast data. This set of several hundred reference chemicals will represent
      numerous structural classes and phenotypic outcomes, including tumorigens,
      developmental and reproductive toxicants, neurotoxicants, and immunotoxicants.
      The ToxCast program will evaluate chemical properties and bioactivity profiles
      across a broad spectrum of data domains: physical-chemical, predicted biological
      activities based on existing structure-activity models, biochemical properties
      based on HTS assays, cell-based phenotypic assays, and genomic and metabolomic
      analyses of cells. These data will be generated through a series of external
      contracts, along with collaborations across EPA, with the National Toxicology
      Program, and with the National Institutes of Health Chemical Genomics Center. The
      resulting multidimensional data set provides an informatics challenge requiring
      appropriate computational methods for integrating various chemical, biological,
      and toxicological data into profiles and models predicting toxicity.

PMID- 16963516
TI  - The transcriptomics of ecological convergence between 2 limnetic coregonine
      fishes (Salmonidae).
AB  - Species living in comparable habitats often display strikingly similar patterns
      of specialization, suggesting that natural selection can lead to predictable
      evolutionary changes. Elucidating the genomic basis underlying such adaptive
      phenotypic changes is a major goal in evolutionary biology. Increasing evidence
      indicates that natural selection would first modulate gene regulation during the
      process of population divergence. Previously, we showed that parallel phenotypic
      adaptations of the dwarf whitefish (Coregonus clupeaformis) ecotype to the
      limnetic trophic niche involved parallel transcriptional changes at the same
      genes involved in muscle contraction and energetic metabolism relative to the
      sympatric normal ecotype. Here, we tested whether the same genes are also
      implicated in a limnetic specialist species, the cisco (Coregonus artedi), which
      is the most likely competitor of dwarf whitefish. Significant upregulation was
      detected in cisco at the same 6 candidate genes functionally involved in
      modulating swimming activity, namely 5 variants of a major protein of fast muscle
      and 1 putative catalytic crystallin enzyme. Moreover, 3 of 5 variants and the
      same putative catalytic crystallin enzyme were upregulated in cisco relative to
      the dwarf ecotype, indicating a greater physiological potential of the former for
      exploiting the limnetic trophic niche. This study provides the first empirical
      evidence that recent, parallel phenotypic evolution toward the use of the same
      ecological niche occupied by a specialist competitor involved similar adaptive
      changes in expression at the same genes. As such, this study provides strong
      support to the general hypothesis that directional selection acting on gene
      regulation may promote rapid phenotypic divergence and ultimately speciation.

PMID- 16963517
TI  - Cingulate activation increases dynamically with response speed under stimulus
      unpredictability.
AB  - Functional magnetic resonance imaging studies of cognition require repeated and
      consistent engagement of the cognitive process under investigation. Activation is
      generally averaged across trials that are assumed to tax a specific mental
      operation or state, whereas intraindividual variability in performance between
      trials is usually considered error variance. A more recent analysis approach
      postulates that these fluctuations can reflect variation in the very process
      taxed by the particular trial type. In the present study, participants responded
      to targets presented randomly in 1 of 4 peripheral locations. By employing a
      function of reaction time (RT) of individual trials as a linear regressor, brain
      regions were identified whose activation varied with RT on a trial-by-trial
      basis. Whole-brain analysis revealed that the anterior cingulate, posterior
      cingulate, and left angular/superior temporal gyri were more active in trials
      with faster RT but only when the target location was unpredictable. No such
      association was seen in trials where the target location was predicted by a
      central cue. These results suggest a role for the cingulate and angular gyri in
      the dynamic regulation of attention to unpredictable events. This is in
      accordance with the function of a default network that is active in the absence
      of top-down-focused attention and is thought to continuously provide resources
      for broad and spontaneous information gathering. Exploiting intertrial
      performance variability may be particularly suitable for capturing such
      spontaneous and elusive phenomena as stimulus-driven processes of attention.

PMID- 16963518
TI  - Thalamic-prefrontal cortical-ventral striatal circuitry mediates dissociable
      components of strategy set shifting.
AB  - The mediodorsal nuclei of thalamus (MD), prefrontal cortex (PFC), and nucleus
      accumbens core (NAc) form an interconnected network that may work together to
      subserve certain forms of behavioral flexibility. The present study investigated
      the functional interactions between these regions during performance of a cross
      maze-based strategy set-shifting task. In Experiment 1, reversible bilateral
      inactivation of the MD via infusions of bupivacaine did not impair simple
      discrimination learning, but did disrupt shifting from response to visual cue
      discrimination strategy, and vice versa. This impairment was due to an increase
      in perseverative errors. In Experiment 2, asymmetrical disconnection
      inactivations of the MD on one side of the brain and PFC on the other also caused
      a perseverative deficit when rats were required to shift from a response to a
      visual cue discrimination strategy, as did disconnections between the PFC and the
      NAc. However, inactivation of the MD on one side of the brain and the NAc
      contralaterally resulted in a selective increase in never-reinforced errors,
      suggesting this pathway is important for eliminating inappropriate strategies
      during set shifting. These data indicate that set shifting is mediated by a
      distributed neural circuit, with separate neural pathways contributing
      dissociable components to this type of behavioral flexibility.

PMID- 16963519
TI  - Biochemical and molecular characterization of AtPAP26, a vacuolar purple acid
      phosphatase up-regulated in phosphate-deprived Arabidopsis suspension cells and
      seedlings.
AB  - A vacuolar acid phosphatase (APase) that accumulates during phosphate (Pi)
      starvation of Arabidopsis (Arabidopsis thaliana) suspension cells was purified to
      homogeneity. The final preparation is a purple APase (PAP), as it exhibited a
      pink color in solution (A(max) = 520 nm). It exists as a 100-kD homodimer
      composed of 55-kD glycosylated subunits that cross-reacted with an anti-(tomato
      intracellular PAP)-IgG. BLAST analysis of its 23-amino acid N-terminal sequence
      revealed that this PAP is encoded by At5g34850 (AtPAP26; one of 29 PAP genes in
      Arabidopsis) and that a 30-amino acid signal peptide is cleaved from the AtPAP26
      preprotein during its translocation into the vacuole. AtPAP26 displays much
      stronger sequence similarity to orthologs from other plants than to other
      Arabidopsis PAPs. AtPAP26 exhibited optimal activity at pH 5.6 and broad
      substrate selectivity. The 5-fold increase in APase activity that occurred in Pi
      deprived cells was paralleled by a similar increase in the amount of a 55-kD anti
      (tomato PAP or AtPAP26)-IgG immunoreactive polypeptide and a >30-fold reduction
      in intracellular free Pi concentration. Semiquantitative reverse transcription
      PCR indicated that Pi-sufficient, Pi-starved, and Pi-resupplied cells contain
      similar amounts of AtPAP26 transcripts. Thus, transcriptional controls appear to
      exert little influence on AtPAP26 levels, relative to translational and/or
      proteolytic controls. APase activity and AtPAP26 protein levels were also up
      regulated in shoots and roots of Pi-deprived Arabidopsis seedlings. We
      hypothesize that AtPAP26 recycles Pi from intracellular P metabolites in Pi
      starved Arabidopsis. As AtPAP26 also exhibited alkaline peroxidase activity, a
      potential additional role in the metabolism of reactive oxygen species is
      discussed.

PMID- 16963520
TI  - Arabidopsis seed development and germination is associated with temporally
      distinct metabolic switches.
AB  - While the metabolic networks in developing seeds during the period of reserve
      accumulation have been extensively characterized, much less is known about those
      present during seed desiccation and subsequent germination. Here we utilized
      metabolite profiling, in conjunction with selective mRNA and physiological
      profiling to characterize Arabidopsis (Arabidopsis thaliana) seeds throughout
      development and germination. Seed maturation was associated with a significant
      reduction of most sugars, organic acids, and amino acids, suggesting their
      efficient incorporation into storage reserves. The transition from reserve
      accumulation to seed desiccation was associated with a major metabolic switch,
      resulting in the accumulation of distinct sugars, organic acids, nitrogen-rich
      amino acids, and shikimate-derived metabolites. In contrast, seed vernalization
      was associated with a decrease in the content of several of the metabolic
      intermediates accumulated during seed desiccation, implying that these
      intermediates might support the metabolic reorganization needed for seed
      germination. Concomitantly, the levels of other metabolites significantly
      increased during vernalization and were boosted further during germination sensu
      stricto, implying their importance for germination and seedling establishment.
      The metabolic switches during seed maturation and germination were also
      associated with distinct patterns of expression of genes encoding metabolism
      associated gene products, as determined by semiquantitative reverse transcription
      polymerase chain reaction and analysis of publicly available microarray data.
      When taken together our results provide a comprehensive picture of the
      coordinated changes in primary metabolism that underlie seed development and
      germination in Arabidopsis. They furthermore imply that the metabolic preparation
      for germination and efficient seedling establishment initiates already during
      seed desiccation and continues by additional distinct metabolic switches during
      vernalization and early germination.

PMID- 16963521
TI  - Extracellular ATP in plants. Visualization, localization, and analysis of
      physiological significance in growth and signaling.
AB  - Extracellular ATP (eATP) in animals is well documented and known to play an
      important role in cellular signaling (e.g. at the nerve synapse). The existence
      of eATP has been postulated in plants; however, there is no definitive
      experimental evidence for its presence or an explanation as to how such a polar
      molecule could exit the plant cell and what physiological role it may play in
      plant growth and development. The presence of eATP in plants (Medicago
      truncatula) was detected by constructing a novel reporter; i.e. fusing a
      cellulose-binding domain peptide to the ATP-requiring enzyme luciferase.
      Application of this reporter to plant roots allowed visualization of eATP in the
      presence of the substrate luciferin. Luciferase activity could be detected in the
      interstitial spaces between plant epidermal cells and predominantly at the
      regions of actively growing cells. The levels of eATP were closely correlated
      with regions of active growth and cell expansion. Pharmacological compounds known
      to alter cytoplasmic calcium levels revealed that ATP release is a calcium
      dependent process and may occur through vesicular fusion, an important step in
      the polar growth of actively growing root hairs. Reactive oxygen species (ROS)
      activity at the root hair tip is not only essential for root hair growth, but
      also dependent on the cytoplasmic calcium levels. Whereas application of
      exogenous ATP and a chitin mixture increased ROS activity in root hairs, no
      changes were observed in response to adenosine, AMP, ADP, and nonhydrolyzable ATP
      (betagammameATP). However, application of exogenous potato (Solanum tuberosum)
      apyrase (ATPase) decreased ROS activity, suggesting that cytoplasmic calcium
      gradients and ROS activity are closely associated with eATP release.

PMID- 16963522
TI  - Building up of the plastid transcriptional machinery during germination and early
      plant development.
AB  - The plastid genome is transcribed by three different RNA polymerases, one is
      called plastid-encoded RNA polymerase (PEP) and two are called nucleus-encoded
      RNA polymerases (NEPs). PEP transcribes preferentially photosynthesis-related
      genes in mature chloroplasts while NEP transcribes preferentially housekeeping
      genes during early phases of plant development, and it was generally thought that
      during plastid differentiation the building up of the NEP transcription system
      precedes the building up of the PEP transcription system. We have now analyzed in
      detail the establishment of the two different transcription systems, NEP and PEP,
      during germination and early seedling development on the mRNA and protein level.
      Experiments have been performed with two different plant species, Arabidopsis
      (Arabidopsis thaliana) and spinach (Spinacia oleracea). Results show that the
      building up of the two different transcription systems is different in the two
      species. However, in both species NEP as well as PEP are already present in
      seeds, and results using Tagetin as a specific inhibitor of PEP activity
      demonstrate that PEP is important for efficient germination, i.e. PEP is already
      active in not yet photosynthetically active seed plastids.

PMID- 16963523
TI  - Identification of drought tolerance determinants by genetic analysis of root
      response to drought stress and abscisic Acid.
AB  - Drought stress is a common adverse environmental condition that seriously affects
      crop productivity worldwide. Due to the complexity of drought as a stress signal,
      deciphering drought tolerance mechanisms has remained a major challenge to plant
      biologists. To develop new approaches to study plant drought tolerance, we
      searched for phenotypes conferred by drought stress and identified the inhibition
      of lateral root development by drought stress as an adaptive response to the
      stress. This drought response is partly mediated by the phytohormone abscisic
      acid. Genetic screens using Arabidopsis (Arabidopsis thaliana) were devised, and
      drought inhibition of lateral root growth (dig) mutants with altered responses to
      drought or abscisic acid in lateral root development were isolated.
      Characterization of these dig mutants revealed that they also exhibit altered
      drought stress tolerance, indicating that this root response to drought stress is
      intimately linked to drought adaptation of the entire plant and can be used as a
      trait to access the elusive drought tolerance machinery. Our study also revealed
      that multiple mechanisms coexist and together contribute to whole-plant drought
      tolerance.

PMID- 16963524
TI  - Isolation of mtpim proves Tnt1 a useful reverse genetics tool in Medicago
      truncatula and uncovers new aspects of AP1-like functions in legumes.
AB  - Comparative studies help shed light on how the huge diversity in plant forms
      found in nature has been produced. We use legume species to study developmental
      differences in inflorescence architecture and flower ontogeny with classical
      models such as Arabidopsis thaliana or Antirrhinum majus. Whereas genetic control
      of these processes has been analyzed mostly in pea (Pisum sativum), Medicago
      truncatula is emerging as a promising alternative system for these studies due to
      the availability of a range of genetic tools. To assess the use of the
      retrotransposon Tnt1 for reverse genetics in M. truncatula, we screened a small
      Tnt1-mutagenized population using degenerate primers for MADS-box genes, known
      controllers of plant development. We describe here the characterization of mtpim,
      a new mutant caused by the insertion of Tnt1 in a homolog to the PROLIFERATING
      INFLORESCENCE MERISTEM (PIM)/APETALA1 (AP1)/SQUAMOSA genes. mtpim shows flower-to
      inflorescence conversion and altered flowers with sepals transformed into leaves,
      indicating that MtPIM controls floral meristem identity and flower development.
      Although more extreme, this phenotype resembles the pea pim mutants, supporting
      the idea that M. truncatula could be used to complement analysis of reproductive
      development already initiated in pea. In fact, our study reveals aspects not
      shown by analysis of pea mutants: that the mutation in the AP1 homolog interferes
      with the specification of floral organs from common primordia and causes
      conversion of sepals into leaves, in addition to true conversion of flowers into
      inflorescences. The isolation of mtpim represents a proof of concept
      demonstrating that Tnt1 populations can be efficiently used in reverse genetics
      screenings in M. truncatula.

PMID- 16963525
TI  - Consistency of polyamine profiles and expression of arginine decarboxylase in
      mitosis during zygotic embryogenesis of Scots pine.
AB  - In this study, we show that both arginine decarboxylase (ADC) protein and mRNA
      transcript are present at different phases of mitosis in Scots pine (Pinus
      sylvestris) zygotic embryogenesis. We also examined the consistency of polyamine
      (PA) profiles with the effective temperature sum, the latter indicating the
      developmental stage of the embryos. PA metabolism was analyzed by fitting
      statistical regression models to the data of free and soluble conjugated PAs, to
      the enzyme activities of ADC and ornithine decarboxylase (ODC), as well as to the
      gene expression of ADC. According to the fitted models, PAs typically had the
      tendency to increase at the early stages but decrease at the late stages of
      embryogenesis. Only the free putrescine fraction remained stable during embryo
      development. The PA biosynthesis strongly preferred the ADC pathway. Both ADC
      gene expression and ADC enzyme activity were substantially higher than putative
      ODC gene expression or ODC enzyme activity, respectively. ADC gene expression and
      enzyme activity increased during embryogenesis, which suggests the involvement of
      transcriptional regulation in the expression of ADC. Both ADC mRNA and ADC
      protein localized in dividing cells of embryo meristems and more specifically
      within the mitotic spindle apparatus and close to the chromosomes, respectively.
      The results suggest the essential role of ADC in the mitosis of plant cells.

PMID- 16963526
TI  - Pathogen-induced Arabidopsis WRKY7 is a transcriptional repressor and enhances
      plant susceptibility to Pseudomonas syringae.
AB  - The Arabidopsis (Arabidopsis thaliana) WRKY7 gene is induced by pathogen
      infection and salicylic acid (SA) treatment and may therefore play a role in
      plant defense responses. Here, we show that WRKY7 is localized in the nucleus,
      recognizes DNA molecules with the W-box (TTGAC) elements, and functions as a
      transcriptional repressor in plant cells. To study its biological functions
      directly, we have characterized both loss-of-function T-DNA insertion and RNAi
      mutants and gain-of-function transgenic overexpression plants for WRKY7 in
      Arabidopsis. The T-DNA insertion and RNAi mutant plants displayed enhanced
      resistance to a virulent strain of the bacterial pathogen Pseudomonas syringae as
      measured by significant decrease in both bacterial growth and symptom development
      as compared to those in wild-type plants. The enhanced resistance in the loss-of
      function mutants was associated with increased induction of SA-regulated
      Pathogenesis-Related 1 (PR1) by the bacterial pathogen. Transgenic plants that
      constitutively overexpress WRKY7 have altered leaf growth and morphology
      strikingly similar to those observed in the previously isolated eds8 mutant
      plants. Like eds8 mutant plants, WRKY7-overexpressing plants supported more
      growth of P. syringae and developed more severe disease symptoms than wild-type
      plants. The enhanced susceptibility of both the WRKY7-overexpressing plants and
      the eds8 mutant correlated with reduced expression of defense-related genes,
      including PR1, but significantly increased accumulation of SA after pathogen
      infection, probably due to reduced negative feedback of SA synthesis. Thus,
      pathogen-induced WRKY7 transcription factor play a negative role in defense
      responses to P. syringae.

PMID- 16963528
TI  - Mechanosensitivity of mouse tracheal ciliary beat frequency: roles for Ca2+,
      purinergic signaling, tonicity, and viscosity.
AB  - Mechanosensitivity is hypothesized to participate in the regulation of ciliary
      beat frequency (CBF) in airway epithelia. To investigate this hypothesis, CBF in
      excised mouse trachea was monitored (microscopy image analysis) while varying
      mucosal shear (perfusate velocity and/or viscosity; planar flow). CBF increased
      within minutes of step increase to steady shear stress as small as 10(-3) Pa and
      decreased within minutes of shear reduction (<or=10(-4) Pa). CBF response was
      directional, being less with cephalad vs. caudal flow, and was reduced in trachea
      from mutant mice lacking P2Y2 receptors, as well as by administration of the Ca2+
      chelator EGTA, the Ca2+ channel inhibitor La3+, the nucleotide phosphohydrolase
      apyrase, the metabolically stabilized adenosine receptor agonist 5'-(N
      ethylcarboxamido)adenosine, the osmotic agent mannitol, and the viscosity
      modifier dextran. Brief exposure to exogenous ATP, a candidate mediator,
      augmented CBF response, although augmentation declined with higher ATP
      concentration (5.0 vs. 0.1 mM) or longer ATP exposure before shear (55 vs. 20
      min). Prolonged extended exposure (45 min) to the metabolically stabilized ATP
      analog ATPgammaS [adenosine 5'-(3-thiotriphosphate), 0.1 mM] inhibited CBF
      response to shear. Furthermore, neither ATP nor ATPgammaS substantially increased
      CBF in the relative absence of shear. With viscosity increase or shear withdrawal
      apyrase evoked CBF stimulation, inhibitable by the adenosine receptor antagonist
      8-(p-sulfophenyl)theophylline. Thus CBF response to shear is finely tuned,
      directional, La3+ sensitive, likely dependent on extracellular Ca2+ and ATP,
      involving P2Y2 and adenosine receptor activations, influenced by shear history,
      tonicity, viscosity, and metabolism/exposure of ATP, and thus reflective of a
      complex interplay of physical and biochemical actions.

PMID- 16963529
TI  - Effects of HSP70.1/3 gene knockout on NF-kappaB-mediated and cytokine-induced
      reduction in alveolar ion and fluid transport.

PMID- 16963530
TI  - Immunological determinants of ventilatory changes induced in mice by dermal
      sensitization and respiratory challenge with toluene diisocyanate.
AB  - The objective of the study was to characterize better the immunologic mechanisms
      underlying a previously developed animal model of chemical-induced asthma. BALB/c
      and severe combined immunodeficiency disease (SCID) mice received toluene
      diisocyanate (TDI) or vehicle on each ear on day 1 and/or day 7. On day 10, they
      were intranasally challenged with TDI or vehicle. Ventilatory function was
      monitored by whole body plethysmography for 40 min after challenge. Reactivity to
      methacholine was measured 23 h later: enhanced pause and actual resistance
      measurements. Pulmonary inflammation was assessed 1, 6, and 24 h after challenge
      by bronchoalveolar lavage (BAL). Tumor necrosis factor-alpha and macrophage
      inflammatory protein (MIP)-2 levels were measured in BAL. Immunological
      parameters included total IgE, IgG1, and IgG2a in serum, lymphocyte populations
      in auricular and cervical lymph nodes, and IL-4 and IFN-gamma levels in
      supernatants of lymph node cells, cultured with or without concanavalin A.
      Ventilatory changes suggestive of airway obstruction and increased methacholine
      reactivity were observed in all TDI-sensitized and TDI intranasally instilled
      mice, except in SCID mice. A neutrophil influx, accompanied by an increase in MIP
      2 levels, was found in BAL of all responding groups 6 and 24 h after intranasal
      challenge. In BALB/c mice an increased level of CD19+ B cells was found in the
      auricular lymph nodes. IL-4 and IFN-gamma levels were increased in supernatants
      of concanavalin A-stimulated auricular lymph node cells from BALB/c mice
      completely treated with TDI. These results indicate that our model is dependent
      on the presence of lymphocytes, but it is not characterized by a preferential
      stimulation of Th1 or Th2 lymphocytes.

PMID- 16963531
TI  - Role of Ca2+ in responses of airway epithelia to Pseudomonas aeruginosa,
      flagellin, ATP, and thapsigargin.
AB  - Neither Pseudomonas aeruginosa nor flagellin affected cytosolic Ca(2+)
      concentration ([Ca](i)) in airway epithelial cell lines JME and Calu-3, but
      bacteria or flagellin activated NF-kappaB, IL-8 promoter, and IL-8 secretion. ATP
      (purinergic agonist) and thapsigargin (blocks Ca(2+) pump, releases endoplasmic
      reticulum Ca(2+), and triggers Ca(2+) entry through plasma membrane channels)
      both increased [Ca](i) but hardly stimulated NF-kappaB and IL-8. ATP and
      thapsigargin elicited larger, synergistic activations of NF-kappaB and IL-8
      secretion when combined with flagellin. BAPTA-AM (to buffer [Ca](i)) or Ca(2+)
      free solution reduced increases in [Ca](i) due to ATP or thapsigargin and also
      reduced NF-kappaB activation and IL-8 secretion triggered by flagellin, ATP,
      thapsigargin, ATP + flagellin, and thapsigargin + flagellin. IL-8 promoter
      analysis showed that AP-1 and CCAAT/enhancer-binding protein (C/EBP)beta/nuclear
      factor for IL-6 (NF-IL6) sites were important for IL-8 expression, and the NF
      kappaB-binding site was critical for activation by all agonists and for
      activation by [Ca](i). Thus increased [Ca](i) was not required for P. aeruginosa-
      or flagellin-activated NF-kappaB and IL-8 expression and secretion, and increased
      [Ca](i) was only weakly stimulatory during activation by ATP or thapsigargin.
      However, ATP- or thapsigargin-induced increases in [Ca](i) synergized with
      flagellin or P. aeruginosa, and buffering or reducing [Ca](i) reduced these
      responses. Thus [Ca](i) plays an important regulatory role in P. aeruginosa- or
      flagellin-activated innate immune responses in airway epithelia. Dose-dependent
      responses indicated that flagellin-ATP synergism occurred most prominently at ATP
      concentrations ([ATP]) > 10 microM and [flagellin] >10(-8) g/ml and during steady
      increases rather than oscillations in [Ca](i).

PMID- 16963532
TI  - Clinical year in review I: diagnostic imaging, asthma, lung transplantation, and
      interventional pulmonology.

PMID- 16963533
TI  - Clinical year in review II: occupational lung disease, pulmonary vascular
      disease, bronchiectasis, and chronic obstructive pulmonary disease.

PMID- 16963534
TI  - Incidence and prevalence of chronic thromboembolic pulmonary hypertension: from
      acute to chronic pulmonary embolism.
AB  - The incidence and prevalence of chronic thromboembolic pulmonary hypertension
      (CTEPH) are yet to be accurately determined and may be significantly
      underestimated. Historically, the occurrence of CTEPH in patients diagnosed with
      acute pulmonary embolism (PE) has been considered rare. Data from autopsy studies
      estimated the incidence of CTEPH at 1-3% overall and at 0.1-0.5% in patients
      surviving acute PE. Data indicate that each year in the United States,
      approximately 600,000 individuals suffer an acute pulmonary embolic event and
      that the annual number of new CTEPH cases in the United States is between 500 and
      2,500. This may underestimate the true frequency of CTEPH because the disease is
      often misdiagnosed due to nonspecific symptoms and variable disease course. A
      monocenter, prospective, longitudinal study assessing symptomatic CTEPH in
      patients with acute PE but without prior venous thromboembolism recently
      estimated the cumulative incidence of CTEPH to be 1.0% 6 mo after PE, 3.1% after
      1 yr, and 3.8% after 2 yr; overall post-PE incidence was approximately 3%.
      Further studies are needed to better define the true rate of CTEPH. Acute embolic
      events can occur without symptoms, and symptomatic PE is often overlooked or
      misdiagnosed in practice. CTEPH is often identified during diagnostic work-up in
      patients with unexplained pulmonary hypertension, many of whom lack medical
      history suggesting previous PE. In a recent study in 142 consecutive patients
      with CTEPH, 90 (63%) had no previous history of symptomatic venous
      thromboembolism. Further prospective epidemiologic studies are needed to better
      define the incidence and prevalence of CTEPH.

PMID- 16963535
TI  - Risk factors for chronic thromboembolic pulmonary hypertension.
AB  - Although there is increasing awareness of the important disease burden associated
      with chronic thromboembolic pulmonary hypertension (CTEPH), the pathogenesis of
      the disease has not been fully elucidated, and factors contributing to its
      development remain poorly defined. Although current data suggest that CTEPH does
      not result from traditional, known thrombophilia or defective plasma
      fibrinolysis, it has been suggested that levels of Factor VIII and
      antiphospholipid antibodies (alongside increased lupus anticoagulant), two
      thrombophilic factors associated with recurrent thrombosis, are elevated in
      association with CTEPH. Differences in the expression of type-1 plasminogen
      activator-inhibitor in CTEPH thrombi (compared with thrombi seen in acute
      pulmonary embolism) suggest that in situ thrombosis within vascularized
      fibromuscular obstructions may favor the persistence of thrombi, contributing to
      disease progression. Additional risk factors have been evaluated in patients with
      CTEPH, including blood groups (which reflect genetically determined erythrocyte
      bound oligosaccharide structures) and lipoprotein (a). Certain medical conditions
      (splenectomy, ventriculo-atrial shunt/(infected) intravenous lines, acute
      pulmonary embolism, and chronic inflammatory states) have been established as
      independent risk factors for CTEPH. In particular, the link between splenectomy
      and CTEPH has gained considerable attention, with speculation that abnormal post
      splenectomy erythrocyte activities or abnormal platelet activation may be
      involved. Although some patients may be genetically susceptible to pulmonary
      arterial hypertension, genetic variants linked with CTEPH have yet to be
      determined. Improved understanding of risk factors for CTEPH is an important
      goal, allowing better targeting of at-risk groups, facilitation of appropriate
      intervention, and potential limitation of disease progression.

PMID- 16963536
TI  - Pulmonary microvascular disease in chronic thromboembolic pulmonary hypertension.
AB  - Distal, small-vessel vasculopathy is generally considered a major contributor to
      the progression of pulmonary hypertension (PH) as chronic thromboembolic
      pulmonary hypertension (CTEPH) develops over time and is a major determinant of
      postoperative outcome after pulmonary endarterectomy (PEA). The pathogenesis and
      natural history of microvascular disease in CTEPH remain uncharacterized.
      Mechanisms for significant distal disease may involve the following processes:
      (1) predominant obstructions of "small" subsegmental elastic pulmonary arteries,
      (2) classical pulmonary arteriopathy of small muscular arteries and arterioles
      distal to nonobstructed vessels, (3) pulmonary arteriopathy of small muscular
      arteries and arterioles distal to totally or partially obstructed vessels.
      Patients in whom obstructed vessels are mainly subsegmental are considered poor
      surgical candidates. Distal pulmonary vasculopathy in both the occluded and
      nonoccluded pulmonary vascular bed is characterized by lesions considered typical
      for idiopathic pulmonary arterial hypertension, including plexiform lesions. The
      pathogenesis and time course of these vascular lesions remain unclear, but may
      involve endothelial and/or platelet production and release of mediators and/or
      altered pulmonary blood flow. The reciprocal contribution of large-vessel
      (operable) and small-vessel lesions in CTEPH is crucial for the indication and
      results of PEA. A combination of investigations is used to identify the extent of
      small-vessel disease, including right-heart catheterization, perfusion lung scan,
      multidetector spiral computed tomography, pulmonary angiography, and pulmonary
      arterial occlusion wave-form analysis. Preliminary evidence suggests that medical
      therapy may provide hemodynamic and clinical benefits for patients in whom PEA
      cannot be applied, in those who have persistent postoperative PH, or in selected
      patients with advanced preoperative hemodynamic changes.

PMID- 16963537
TI  - State-of-the-art imaging techniques in chronic thromboembolic pulmonary
      hypertension.
AB  - It is important to differentiate chronic thromboembolic pulmonary hypertension
      (CTEPH) from other forms of pulmonary hypertension (PH) to target treatment and
      optimize therapeutic outcome. Misdiagnosis is common, and high-quality imaging is
      essential if CTEPH is to be diagnosed correctly. In addition to making a
      diagnosis, imaging helps identify patients for surgery, aids surgical planning,
      and provides postsurgical monitoring. Ventilation-perfusion scintigraphy and
      pulmonary angiography have been the mainstay of diagnosis and surgical assessment
      for many years, but cross-sectional techniques are rapidly taking over.
      Echocardiography is used to confirm or refute the presence of PH and to identify
      cardiac causes if PH is present. For patients with PH but no evidence of cardiac
      disease, multislice computed tomography (CT) is the next best step. CT
      distinguishes CTEPH from idiopathic arterial PH, evaluates underlying lung
      disease, and may help identify rarer causes of PH. CT is quick, widely available,
      and inexpensive. There is, however, a significant radiation burden, and it is
      unsuitable for serial examinations. Magnetic resonance (MR) involves no ionizing
      radiation and makes an ideal alternative. When combined with techniques for
      measuring ventricular function and blood flow, MR provides unique insight into
      structure and function. CT and MR are complementary techniques, and together they
      represent the future of imaging in PH. How they might be used in routine clinical
      practice is presented as a diagnostic algorithm developed at Papworth Hospital,
      the United Kingdom's national center for surgical treatment of CTEPH.

PMID- 16963538
TI  - Assessment of operability in chronic thromboembolic pulmonary hypertension.
AB  - Pulmonary endarterectomy surgery (PEA) offers the possibility of a cure for
      patients suffering from chronic thromboembolic pulmonary hypertension (CTEPH).
      Despite growing experience worldwide, the approach and criteria for patient
      selection remain variable and center- or expert-dependent. A significant
      proportion of patients with CTEPH may be turned down for PEA for a number of
      reasons, most frequently over concerns of distal or inaccessible disease.
      Although traditional preoperative testing and currently available tools are
      adequate in identifying the presence of proximal disease in CTEPH, they provide
      only limited information on the status of the microvasculature. Because
      persistent pulmonary hypertension is the most important determinant of post-PEA
      outcome, the preoperative identification of patients with CTEPH with concomitant
      small-vessel disease and/or microvascular disease is crucial. Pulmonary vascular
      resistance (PVR) is a useful parameter for assessing potential concomitant small
      vessel disease. By assessing the relative contribution of small vessels to the
      PVR, the pulmonary artery occlusion technique represents a promising tool for
      determining the risk of surgery in patients with high PVR. More information is
      required regarding the potential value or risk of preoperative medical therapies.
      Although traditional surgical classification of CTEPH takes place
      intraoperatively, there is a need for a preoperative classification system and
      consensus on operability. A preliminary preoperative classification system has
      been proposed.

PMID- 16963539
TI  - Techniques and outcomes of pulmonary endarterectomy for chronic thromboembolic
      pulmonary hypertension.
AB  - Cardiopulmonary function in patients with chronic thromboembolic pulmonary
      hypertension can almost be normalized by pulmonary endarterectomy. The procedure
      involves the removal of organized and incorporated fibrous obstructive tissue
      from the pulmonary arteries during circulatory arrest under deep hypothermia.
      Mortality rates reported for patients who have undergone pulmonary endarterectomy
      range from 4 to 24%. The operation is not an embolectomy but a true
      endarterectomy. After proximal intrapericardial pulmonary artery incision, the
      correct endarterectomy plane is established and circumferentially followed down
      to the lobar, segmental, and sometimes subsegmental pulmonary artery branches in
      each lobe. Completion of the endarterectomy procedure in one lung is usually
      possible within a 15-min period of circulatory arrest. This is followed by
      reperfusion and another period of circulatory arrest for the endarterectomy on
      the contralateral side. Additional cardiac procedures can be performed after
      arteriotomy closure, during the rewarming period, if necessary. The outcomes with
      regard to functional status, quality of life, hemodynamics, right-ventricular
      function, and gas exchange are very favorable. After surgery, significant and
      persistent decreases of pulmonary artery pressures and pulmonary vascular
      resistance are observed in a large majority of patients. Cardiac output is
      increased and right-heart function is persistently improved. Postoperative
      management of patients undergoing pulmonary endarterectomy can be challenging.
      Important complications are persistent pulmonary arterial hypertension due to
      inadequate endarterectomy or significant secondary vasculopathy, and reperfusion
      edema in the endarterectomized parts of the lung. Adequate postoperative care is
      therefore essential. Preoperative hemodynamic severity and the site of anatomic
      obstruction are believed to be key predictors of postoperative outcome.

PMID- 16963540
TI  - Medical therapies for chronic thromboembolic pulmonary hypertension: an evolving
      treatment paradigm.
AB  - Pulmonary endarterectomy (PEA) is recommended as the treatment of choice for
      eligible patients with chronic thromboembolic pulmonary hypertension (CTEPH).
      However, only a proportion of patients fulfill the criteria for surgical
      intervention. In addition, operated patients with CTEPH may experience a gradual
      hemodynamic and symptomatic decline related to a secondary hypertensive
      arteriopathy in the small precapillary pulmonary vessels. It has also been
      questioned what can be done to reduce risks from PEA surgery to improve outcome
      in "high risk" patients with CTEPH with substantial impairment of pulmonary
      hemodynamics before surgery. Such patients may benefit from preoperative
      reduction of pulmonary vascular resistance by means of medical therapy.
      Conventional medical treatments, such as anticoagulation, diuretics, digitalis,
      and chronic oxygen therapy, show low efficacy in the treatment of CTEPH as they
      do not affect underlying disease processes. Over the last decade, several novel
      therapies have been developed for pulmonary arterial hypertension (PAH),
      including prostacyclin analogs (epoprostenol, beraprost, iloprost), endothelin
      receptor antagonists (bosentan, sitaxsentan, ambrisentan), and phosphodiesterase
      5 inhibitors (sildenafil). Evidence of efficacy in PAH, coupled with studies
      showing histopathologic similarities between CTEPH and PAH, provides a rationale
      to extend the use of some of these medications to the treatment of CTEPH.
      However, direct evidence from clinical trials in CTEPH is limited to date. This
      article reviews evidence supporting, and issues surrounding, the possible use of
      novel PAH medications in CTEPH.

PMID- 16963541
TI  - Current and future management of chronic thromboembolic pulmonary hypertension:
      from diagnosis to treatment responses.
AB  - Although pulmonary endarterectomy (PEA) has been proven a very effective
      treatment for chronic thromboembolic pulmonary hypertension, it cannot be
      performed in a substantial proportion of patients. Here, we outline a proposed
      treatment algorithm, outlining therapeutic alternatives: (1) PEA should be
      considered as the first treatment option, where possible; (2) medical
      intervention is a possible option in inoperable patients and those with
      significant arteriopathy, although only chronic anticoagulation has been widely
      used to date (advanced medical treatment options could include prostanoids,
      endothelin receptor antagonists, or phosphodiesterase-5 inhibitors, but
      randomized clinical trials are required); (3) pulmonary hypertension is likely to
      persist after PEA in patients with significant small-vessel arteriopathy,
      resulting in poor clinical outcome and increased perioperative mortality (medical
      therapy could also be applied here); (4) anticoagulation therapy and, possibly,
      advanced medical treatment with careful monitoring may provide benefits in
      patients with mild or asymptomatic disease; (5) if medical therapy begins to
      fail, PEA should be offered without delay to avoid progression to severe,
      secondary arteriopathy; (6) in the absence of severe comorbidity, lung
      transplantation may be undertaken where PEA has failed, in nonresponders to
      medical therapy, and in patients with progressive arteriopathy; (7) in patients
      not eligible for PEA due to collateral and/or surgically inaccessible lesions,
      balloon angioplasty may be a possible alternative at some centers, but is
      experimental and requires further assessment. Continued research and clinical
      trials investigating possible applications of new medical treatments are
      required.

PMID- 16963542
TI  - Controversies, uncertainties and future research on the treatment of chronic
      thromboembolic pulmonary hypertension.
AB  - A number of controversies exist regarding the pathophysiology, natural history,
      diagnosis, and treatment of chronic thromboembolic pulmonary hypertension
      (CTEPH). Although CTEPH is regarded by many to be a complication of pulmonary
      embolism (PE) arising subsequent to venous thromboembolism (VTE)-the embolic
      hypothesis-it has been suggested that PE is rarely the sole cause of CTEPH and
      that primary arteriopathy with secondary in situ thrombosis may be relevant in
      the pathogenesis and progression of the disease-the thrombotic hypothesis. A
      number of lines of evidence support this. Only about half of patients referred
      with suspected CTEPH have a history of VTE. In addition, data suggest that acute
      PE is often diagnosed, and possibly misdiagnosed, in patients with preexisting
      pulmonary artery pathology. There has been much research and debate on the
      importance of distal arteriopathy in both the initiation and progression of
      CTEPH. Histopathologic studies have indicated distinct overlap in the
      microvascular pathology of CTEPH and idiopathic pulmonary arterial hypertension
      (IPAH), and it has been queried whether class IV CTEPH (increased pulmonary
      vascular resistance due to distal arteriopathy in the absence of central
      organized thrombi) and IPAH represent extremes of a disease continuum. Together,
      these issues may impact on effective diagnosis, preoperative screening criteria
      for pulmonary endarterectomy surgery, and the likelihood of persistent pulmonary
      hypertension or even mortality after surgery. They are particularly relevant when
      considering the possible future use of medical therapies in long-term disease
      management.

PMID- 16963544
TI  - Chronic obstructive pulmonary disease: the disease and its burden to society.
AB  - Chronic obstructive pulmonary disease (COPD) is a multicomponent disease with
      inflammation at its core, and a major cause of morbidity and mortality. It
      represents a substantial economic and social burden throughout the world.
      Currently, COPD is the fifth leading cause of death worldwide, and despite
      advances in management, mortality is expected to increase in the coming decades,
      in marked contrast to other chronic diseases, such as heart disease and stroke,
      where there have been considerable decreases in mortality. On a patient level,
      the burden of COPD to patients and their families and carers is high, both in
      terms of health-related quality of life and health status. Health care providers
      and patients often underestimate the substantial morbidity associated with COPD;
      the condition is also frequently underdiagnosed and undertreated, which further
      compromises morbidity. Reducing the burden of COPD requires better evaluation and
      diagnosis, as well as improved management of chronic symptoms. As exacerbations
      and hospitalizations represent an important driver of the cost and morbidity of
      COPD, high priority should be given to interventions aimed at delaying the
      progression of disease, preventing exacerbations, and reducing the risk of
      comorbidities to alleviate the clinical and economic burden of disease.

PMID- 16963545
TI  - Pharmacotherapy for mortality reduction in chronic obstructive pulmonary disease.
AB  - Despite rapid advances in our understanding of its pathophysiology, chronic
      obstructive pulmonary disease (COPD) remains incurable. Although bronchodilators
      and theophyllines are commonly used to treat symptoms of dyspnea and cough and to
      acutely improve lung function, they do not modify the long-term decline in
      FEV(1). The principal goals of current COPD pharmacotherapy are to reduce
      exacerbations, improve health status, and prolong survival. There is strong
      evidence, including data from randomized clinical trials, that indicates inhaled
      corticosteroids alone, or in combination with a long-acting beta(2)-adrenoceptor
      agonist, improve patient symptoms, reduce morbidity, and perhaps even prolong
      survival in COPD. A recent individual patient-based meta-analysis of randomized,
      placebo-controlled trials of inhaled corticosteroids in COPD indicated that
      mortality over 3-4 yr was 27% lower in the group that received inhaled
      corticosteroids compared with the group that received placebo. Several short-term
      follow-up trials have also suggested a reduction in mortality with a combination
      of long-acting beta(2)-agonist and inhaled corticosteroids, and a large, long
      term study that is currently ongoing (the Toward a Revolution in COPD Health
      [TORCH] study) will provide data on the effects of fluticasone propionate and
      salmeterol in combination on all-cause mortality. This article reviews some of
      the relevant epidemiologic and pathophysiologic processes that affect mortality
      in COPD and critically examines the effect of current COPD therapies on
      mortality.

PMID- 16963546
TI  - Economic modeling in chronic obstructive pulmonary disease.
AB  - Calculating the cost-effectiveness of interventions is an important step in
      accurately assessing the health and financial burdens of a disease. Although
      clinical trials that include cost data can be used to compare the cost
      effectiveness of specific interventions, they only deal with outcomes within the
      time frame of the trial. Health economic models can synthesize epidemiologic,
      clinical, economic, and quality-of-life data from many different sources and
      extrapolate results to a point many years in the future. The models generally
      compare interventions with respect to the costs per life-year gained or per
      quality-adjusted life-year gained. The use of health economic models to assess
      the economic burden of chronic obstructive pulmonary disease (COPD) and the value
      of interventions is growing, and will continue to do so as the burden of the
      disease is better appreciated. Several COPD disease-state models have been
      described; each uses a consistent definition of COPD severity that is based on
      FEV(1)% predicted, but the models differ in the allowed transitions, disease
      progression estimates, utility weights, and costs. This article reviews COPD
      health economic models and discusses the importance of survival benefits and
      utilities (health state valuations) for COPD in economic models.

PMID- 16963547
TI  - Chronic obstructive pulmonary disease, risk factors, and outcome trials:
      comparisons with cardiovascular disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a major health problem and now
      ranks fifth in terms of the global burden of disease. Although COPD is a disease
      that is characterized by progressive respiratory symptoms and functional decline,
      exacerbations pose the greatest risk for morbidity and early mortality, have a
      dramatic effect on quality of life, and are the most significant source of health
      care expenditure. To improve survival and reduce costs, it is critical to develop
      effective programs designed to reduce the frequency and severity of exacerbations
      for these patients. With limited health care resources, efficient and effective
      management of COPD ideally involves identifying and focusing efforts on
      individuals at particular risk. In the development of an appropriate multimodal
      strategy, lessons could be learned from the evolution of guidelines and
      management of cardiovascular disease, in particular heart failure, which has many
      parallels with COPD in terms of prevalence, prognosis, and impact on patient
      quality of life. There is a need for large prospective trials in COPD, based on
      hard clinical outcomes such as death, which, together with physician and patient
      education, will help to drive improvements in clinical management.

PMID- 16963548
TI  - Guidelines for chronic obstructive pulmonary disease treatment and issues of
      implementation.
AB  - Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and
      mortality worldwide. Treatment advances over the last decade, although limited,
      have precipitated the development of clinical practice guidelines, with the aim
      of improving the quality of care received by patients through fostering evidence
      based decision making and accelerating the application of new advances to
      everyday practice. Of the COPD guidelines that have been developed, those
      developed through the Global Initiative for Chronic Obstructive Lung Disease
      (GOLD), initially a joint activity between the U.S. National Heart, Lung, and
      Blood Institute and the World Health Organization, and the National Institute of
      Clinical Excellence (NICE) in the United Kingdom have both published their
      methods for evaluation of evidence. These comprehensive guidelines cover all
      aspects of the disease, with the aim of providing the basis for local care
      pathways. The guideline development process includes evaluation of the evidence,
      development of the guideline, and dissemination of the findings. Efforts to
      enhance guideline effectiveness have focused on improving the methods and
      approaches to implementation, which requires an appreciation of the issues that
      stop translation of guideline definitions of best practice into improved patient
      care. A variety of questions remain unanswered in the clinical management of
      COPD, including the definition of outcome measures that move beyond lung
      function, the potential application of multidimensional grading systems that
      assess respiratory and systemic expressions of COPD and that could possibly
      better categorize and predict outcome in these patients, and the impact of new
      clinical trial findings. Large ongoing outcome studies may also have an effect on
      defining best practice within future guideline recommendations.

PMID- 16963549
TI  - An integrated approach to functional genomics: construction of a novel reporter
      gene fusion library for Sinorhizobium meliloti.
AB  - As a means of investigating gene function, we developed a robust transcription
      fusion reporter vector to measure gene expression in bacteria. The vector,
      pTH1522, was used to construct a random insert library for the Sinorhizobium
      meliloti genome. pTH1522 replicates in Escherichia coli and can be transferred
      to, but cannot replicate in, S. meliloti. Homologous recombination of the DNA
      fragments cloned in pTH1522 into the S. meliloti genome generates transcriptional
      fusions to either the reporter genes gfp(+) and lacZ or gusA and rfp, depending
      on the orientation of the cloned fragment. Over 12,000 fusion junctions in 6,298
      clones were identified by DNA sequence analysis, and the plasmid clones were
      recombined into S. meliloti. Reporter enzyme activities following growth of these
      recombinants in complex medium (LBmc) and in minimal medium with glucose or
      succinate as the sole carbon source allowed the identification of genes highly
      expressed under one or more growth condition and those expressed at very low to
      background levels. In addition to generating reporter gene fusions, the vector
      allows Flp recombinase-directed deletion formation and gene disruption, depending
      on the nature of the cloned fragment. We report the identification of genes
      essential for growth on complex medium as deduced from an inability to recover
      recombinants from pTH1522 clones that carried fragments internal to gene or
      operon transcripts. A database containing all the gene expression activities
      together with a web interface showing the precise locations of reporter fusion
      junctions has been constructed (www.sinorhizobium.org).

PMID- 16963550
TI  - Use of native lactococci as vehicles for delivery of DNA into mammalian
      epithelial cells.
AB  - The use of the food-grade bacterium Lactococcus lactis as a DNA delivery vehicle
      at the mucosal level is an attractive DNA vaccination strategy. Previous
      experiments showed that recombinant L. lactis expressing the Listeria
      monocytogenes inlA gene can deliver a functional gene into mammalian cells. Here,
      we explored the potential use of noninvasive L. lactis strains as a DNA delivery
      vehicle. We constructed two Escherichia coli-L. lactis shuttle plasmids,
      pLIG:BLG1 and pLIG:BLG2, containing a eukaryotic expression cassette with the
      cDNA of bovine beta-lactoglobulin (BLG). The greatest BLG expression after
      transfection of Cos-7 cells was obtained with pLIG:BLG1, which was then used to
      transform L. lactis MG1363. The resulting L. lactis strain MG1363(pLIG:BLG1) was
      not able to express BLG. The potential of L. lactis as a DNA delivery vehicle was
      analyzed by detection of BLG in Caco-2 human colon carcinoma cells after 3 h of
      coincubation with (i) purified pLIG:BLG1, (ii) MG1363(pLIG:BLG1), (iii) a mix of
      MG1363(pLIG) and purified pLIG:BLG1, and (iv) MG1363. Both BLG cDNA and BLG
      expression were detected only in Caco-2 cells coincubated with MG1363(pLIG:BLG1).
      There was a decrease in the BLG cDNA level in Caco-2 cells between 24 and 48 h
      after coincubation. BLG expression by Caco-2 cells started at 24 h and increased
      between 24 and 72 h. BLG secretion by Caco-2 cells started 48 h after
      coincubation with MG1363(pLIG:BLG1). We conclude that lactococci can deliver BLG
      cDNA into mammalian epithelial cells, demonstrating their potential to deliver in
      vivo a DNA vaccine.

PMID- 16963551
TI  - Genetic characterization of the resorcinol catabolic pathway in Corynebacterium
      glutamicum.
AB  - Corynebacterium glutamicum grew on resorcinol as a sole source of carbon and
      energy. By genome-wide data mining, two gene clusters, designated NCgl1110
      NCgl1113 and NCgl2950-NCgl2953, were proposed to encode putative proteins
      involved in resorcinol catabolism. Deletion of the NCgl2950-NCgl2953 gene cluster
      did not result in any observable phenotype changes. Disruption and
      complementation of each gene at NCgl1110-NCgl1113, NCgl2951, and NCgl2952
      indicated that these genes were involved in resorcinol degradation. Expression of
      NCgl1112, NCgl1113, and NCgl2951 in Escherichia coli revealed that NCgl1113 and
      NCgl2951 both coded for hydroxyquinol 1,2-dioxygenases and NCgl1112 coded for
      maleylacetate reductases. NCgl1111 encoded a putative monooxygenase, but this
      putative hydroxylase was very different from previously functionally identified
      hydroxylases. Cloning and expression of NCgl1111 in E. coli revealed that
      NCgl1111 encoded a resorcinol hydroxylase that needs NADPH as a cofactor. E. coli
      cells containing Ncgl1111 and Ncgl1113 sequentially converted resorcinol into
      maleylacetate. NCgl1110 and NCgl2950 both encoded putative TetR family
      repressors, but only NCgl1110 was transcribed and functional. NCgl2953 encoded a
      putative transporter, but disruption of this gene did not affect resorcinol
      degradation by C. glutamicum. The function of NCgl2953 remains unclear.

PMID- 16963553
TI  - Effects of mutations in the substrate-binding domain of poly[(R)-3
      hydroxybutyrate] (PHB) depolymerase from Ralstonia pickettii T1 on PHB
      degradation.
AB  - Poly[(R)-3-hydroxybutyrate] (PHB) depolymerase from Ralstonia pickettii T1
      (PhaZ(RpiT1)) adsorbs to denatured PHB (dPHB) via its substrate-binding domain
      (SBD) to enhance dPHB degradation. To evaluate the amino acid residues
      participating in dPHB adsorption, PhaZ(RpiT1) was subjected to a high-throughput
      screening system consisting of PCR-mediated random mutagenesis targeted to the
      SBD gene and a plate assay to estimate the effects of mutations in the SBD on
      dPHB degradation by PhaZ(RpiT1). Genetic analysis of the isolated mutants with
      lowered activity showed that Ser, Tyr, Val, Ala, and Leu residues in the SBD were
      replaced by other residues at high frequency. Some of the mutant enzymes, which
      contained the residues replaced at high frequency, were applied to assays of dPHB
      degradation and adsorption, revealing that those residues are essential for full
      activity of both dPHB degradation and adsorption. These results suggested that
      PhaZ(RpiT1) adsorbs on the surface of dPHB not only via hydrogen bonds between
      hydroxyl groups of Ser in the enzyme and carbonyl groups in the PHB polymer but
      also via hydrophobic interaction between hydrophobic residues in the enzyme and
      methyl groups in the PHB polymer. The L441H enzyme, which displayed lower dPHB
      degradation and adsorption abilities, was purified and applied to a dPHB
      degradation assay to compare it with the wild-type enzyme. The kinetic analysis
      of the dPHB degradation suggested that lowering the affinity of the SBD towards
      dPHB causes a decrease in the dPHB degradation rate without the loss of its
      hydrolytic activity for the polymer chain.

PMID- 16963552
TI  - Identification of specific gene sequences conserved in contemporary epidemic
      strains of Salmonella enterica.
AB  - Genetic elements specific to recent and contemporary epidemic strains of
      Salmonella enterica were identified using comparative genomic analysis. Two
      epidemic multidrug-resistant (MDR) strains, MDR Salmonella enterica serovar
      Typhimurium definitive phage type 104 (DT104) and cephalosporin-resistant MDR
      Salmonella enterica serovar Newport, and an epidemic pansusceptible strain,
      Salmonella serovar Typhimurium DT160, were subjected to Salmonella gene
      microarray and suppression subtractive hybridization analyses. Their genome
      contents were compared with those of coexisting sporadic strains matched by
      serotype, geographic and temporal distribution, and host species origin. These
      paired comparisons revealed that epidemic strains of S. enterica had specific
      genes and gene regions that were shared by isolates of the same subtype. Most of
      these gene sequences are related to mobile genetic elements, including phages,
      plasmids, and plasmid-like and transposable elements, and some genes may encode
      proteins conferring growth or survival advantages. The emergence of epidemic MDR
      strains may therefore be associated with the presence of fitness-associated
      genetic factors in addition to their antimicrobial resistance genes.

PMID- 16963554
TI  - Genetic differences between blight-causing Erwinia species with differing host
      specificities, identified by suppression subtractive hybridization.
AB  - PCR-based subtractive hybridization was used to isolate sequences from Erwinia
      amylovora strain Ea110, which is pathogenic on apples and pears, that were not
      present in three closely related strains with differing host specificities: E.
      amylovora MR1, which is pathogenic only on Rubus spp.; Erwinia pyrifoliae Ep1/96,
      the causal agent of shoot blight of Asian pears; and Erwinia sp. strain Ejp556,
      the causal agent of bacterial shoot blight of pear in Japan. In total, six
      subtractive libraries were constructed and analyzed. Recovered sequences included
      type III secretion components, hypothetical membrane proteins, and ATP-binding
      proteins. In addition, we identified an Ea110-specific sequence with homology to
      a type III secretion apparatus component of the insect endosymbiont Sodalis
      glossinidius, as well as an Ep1/96-specific sequence with homology to the
      Yersinia pestis effector protein tyrosine phosphatase YopH.

PMID- 16963555
TI  - Intraspecific variation in growth and morphology of the bloom-forming
      cyanobacterium Microcystis aeruginosa.
AB  - In the laboratory, we documented large variation in the morphology, toxicity, and
      maximum population growth rates for 32 Microcystis aeruginosa strains isolated
      from 12 lakes. Growth rates and mean colony sizes varied significantly across
      strains and were positively correlated. However, growth rates were unrelated to
      toxin production.

PMID- 16963556
TI  - Complete nucleotide sequence of an exogenously isolated plasmid, pLB1, involved
      in gamma-hexachlorocyclohexane degradation.
AB  - The alpha-proteobacterial strain Sphingobium japonicum UT26 utilizes a highly
      chlorinated pesticide, gamma-hexachlorocyclohexane (gamma-HCH), as a sole source
      of carbon and energy, and haloalkane dehalogenase LinB catalyzes the second step
      of gamma-HCH degradation in UT26. Functional complementation of a linB mutant of
      UT26, UT26DB, was performed by the exogenous plasmid isolation technique using
      HCH-contaminated soil, leading to our successful identification of a plasmid,
      pLB1, carrying the linB gene. Complete sequencing analysis of pLB1, with a size
      of 65,998 bp, revealed that it carries (i) 50 totally annotated coding sequences,
      (ii) an IS6100 composite transposon containing two copies of linB, and (iii)
      potential genes for replication, maintenance, and conjugative transfer with low
      levels of similarity to other homologues. A minireplicon assay demonstrated that
      a 2-kb region containing the predicted repA gene and its upstream region of pLB1
      functions as an autonomously replicating unit in UT26. Furthermore, pLB1 was
      conjugally transferred from UT26DB to other alpha-proteobacterial strains but not
      to any of the beta- or gamma-proteobacterial strains examined to date. These
      results suggest that this exogenously isolated novel plasmid contributes to the
      dissemination of at least some genes for gamma-HCH degradation in the natural
      environment. To the best of our knowledge, this is the first detailed report of a
      plasmid involved in gamma-HCH degradation.

PMID- 16963557
TI  - System for determining the relative fitness of multiple bacterial populations
      without using selective markers.
AB  - A device for simultaneously measuring the relative fitness of multiple bacterial
      populations was developed and evaluated. The new device eliminates the need to
      construct strains with selectively neutral markers so that strains can be readily
      distinguished, and it provides a means to perform multispecies competition
      experiments.

PMID- 16963558
TI  - Influenza A virus NS1 protein binds p85beta and activates phosphatidylinositol-3
      kinase signaling.
AB  - Influenza A virus NS1 is a multifunctional protein, and in virus-infected cells
      NS1 modulates a number of host-cell processes by interacting with cellular
      factors. Here, we report that NS1 binds directly to p85beta, a regulatory subunit
      of phosphatidylinositol-3-kinase (PI3K), but not to the related p85alpha subunit.
      Activation of PI3K in influenza virus-infected cells depended on genome
      replication, and showed kinetics that correlated with NS1 expression.
      Additionally, it was found that expression of NS1 alone was sufficient to
      constitutively activate PI3K, causing the phosphorylation of a downstream
      mediator of PI3K signal transduction, Akt. Mutational analysis of a potential SH2
      binding motif within NS1 indicated that the highly conserved tyrosine at residue
      89 is important for both the interaction with p85beta, and the activation of
      PI3K. A mutant influenza virus (A/Udorn/72) expressing NS1 with the Y89F amino
      acid substitution exhibited a small-plaque phenotype, and grew more slowly in
      tissue culture than WT virus. These data suggest that activation of PI3K
      signaling in influenza A virus-infected cells is important for efficient virus
      replication.

PMID- 16963559
TI  - AL-57, a ligand-mimetic antibody to integrin LFA-1, reveals chemokine-induced
      affinity up-regulation in lymphocytes.
AB  - Affinity of integrin lymphocyte function-associated antigen 1 (LFA-1) is enhanced
      by conformational changes from the low-affinity closed form to the high-affinity
      (HA) open form of the ligand-binding inserted (I) domain as shown by work with
      purified I domains. However, affinity up-regulation of LFA-1 on the cell surface
      by physiological agonists such as chemokines has yet to be demonstrated by
      monovalent reagents. We characterize a mAb, AL-57 (activated LFA-1 clone 57),
      that has been developed by phage display that selectively targets the HA open
      conformation of the LFA-1 I domain. AL-57 discriminates among low-affinity,
      intermediate-affinity, and HA states of LFA-1. Furthermore, AL-57 functions as a
      ligand mimetic that binds only upon activation and requires Mg2+ for binding.
      Compared with the natural ligand intercellular adhesion molecule-1, AL-57 shows a
      tighter binding to the open I domain and a 250-fold slower off rate. Monovalent
      Fab AL-57 demonstrates affinity increases on a subset (approximately 10%) of
      lymphocyte cell surface LFA-1 molecules upon stimulation with CXCL-12 (CXC
      chemokine ligand 12). Affinity up-regulation correlates with global
      conformational changes of LFA-1 to the extended form. Affinity increase
      stimulated by CXCL-12 is transient and peaks 2 to 5 min after stimulation.

PMID- 16963560
TI  - Identification of DNMT1 (DNA methyltransferase 1) hypomorphs in somatic knockouts
      suggests an essential role for DNMT1 in cell survival.
AB  - Previous studies have shown that DNA methyltransferase (Dnmt) 1 is required for
      maintenance of bulk DNA methylation and is essential for mouse development.
      However, somatic disruption of DNMT1 in the human cancer cell line HCT116 was not
      lethal and caused only minor decreases in methylation. Here, we report the
      identification of a truncated DNMT1 protein, which was generated by the
      disruption of DNMT1 in HCT116 cells. The truncated protein, which had parts of
      the regulatory N-terminal domain deleted but preserved the catalytic C-terminal
      domain, was present at different levels in all DNMT1 single-knockout and
      DNMT1/DNMT3b double-knockout cell lines tested and retained hemimethylase
      activity. DNMT1 RNAi resulted in decreased cell viability in WT and knockout
      cells and further loss of DNA methylation in DNMT1 knockout cells. Furthermore,
      we observed a delay in methylation after replication and an increase in
      hemimethylation of specific CpG sites in cells expressing the truncated protein.
      Remethylation studies after drug-induced hypomethylation suggest a putative role
      of DNMT1 in the de novo methylation of a subtelomeric repeat, D4Z4, which is lost
      in cells lacking full-length DNMT1. Our data suggest that DNMT1 might be
      essential for maintenance of DNA methylation, proliferation, and survival of
      cancer cells.

PMID- 16963561
TI  - Reconstitution of full-round uridine-deletion RNA editing with three recombinant
      proteins.
AB  - Uridine (U)-insertion/deletion RNA editing in trypanosome mitochondria involves
      an initial cleavage of the preedited mRNA at specific sites determined by the
      annealing of partially complementary guide RNAs. An involvement of two RNase III
      containing core editing complex (L-complex) proteins, MP90 (KREPB1) and MP61
      (KREPB3) in, respectively, U-deletion and U-insertion editing, has been
      suggested, but these putative enzymes have not been characterized or expressed in
      active form. Recombinant MP90 proteins from Trypanosoma brucei and Leishmania
      major were expressed in insect cells and cytosol of Leishmania tarentolae,
      respectively. These proteins were active in specifically cleaving a model U
      deletion site and not a U-insertion site. Deletion or mutation of the RNase III
      motif abolished this activity. Full-round guide RNA (gRNA)-mediated in vitro U
      deletion editing was reconstituted by a mixture of recombinant MP90 and
      recombinant RNA editing exonuclease I from L. major, and recombinant RNA editing
      RNA ligase 1 from L. tarentolae. MP90 is designated REN1, for RNA-editing
      nuclease 1.

PMID- 16963562
TI  - A tropomyosin-related kinase B ligand is required for ERK activation, long-term
      synaptic facilitation, and long-term memory in aplysia.
AB  - BDNF, which acts through tropomyosin-related kinase B (TrkB) receptors during
      mammalian development, also enhances long-term synaptic facilitation (LTF) in
      adult Aplysia. Because LTF is a substrate for long-term memory (LTM) in Aplysia,
      we examined the requirement of a secreted TrkB ligand in LTM formation at
      molecular, synaptic, and behavioral levels. Using an extracellular fusion protein
      that sequesters secreted TrkB ligands, we show that TrkB function is required for
      serotonin-induced activation of extracellular signal-regulated kinase, tail nerve
      shock-induced LTF in the CNS, and tail shock-induced LTM but is not necessary for
      short-term synaptic facilitation or short-term memory. These results show that a
      secreted growth factor, acting through a TrkB signaling cascade, is critical for
      the induction of long-lasting plasticity and memory formation in Aplysia.

PMID- 16963563
TI  - Alternative inclusion of fibroblast growth factor receptor 2 exon IIIc in Dunning
      prostate tumors reveals unexpected epithelial mesenchymal plasticity.
AB  - In epithelial cells, alternative splicing of fibroblast growth factor receptor 2
      (FGFR2) transcripts leads to the expression of the FGFR2(IIIb) isoform, whereas
      in mesenchymal cells, the same process results in the synthesis of FGFR2(IIIc).
      Expression of the FGFR2(IIIc) isoform during prostate tumor progression suggests
      a disruption of the epithelial character of these tumors. To visualize the use of
      FGFR2 exon IIIc in prostate AT3 tumors in syngeneic rats, we constructed minigene
      constructs that report on alternative splicing. Imaging these alternative
      splicing decisions revealed unexpected mesenchymal-epithelial transitions in
      these primary tumors. These transitions were observed more frequently where tumor
      cells were in contact with stroma. Indeed, these transitions were frequently
      observed among lung micrometastases in the organ parenchyma and immediately
      adjacent to blood vessels. Our data suggest an unforeseen relationship between
      epithelial mesenchymal plasticity and malignant fitness.

PMID- 16963564
TI  - Solution structure of the complex between poxvirus-encoded CC chemokine inhibitor
      vCCI and human MIP-1beta.
AB  - Chemokines (chemotactic cytokines) comprise a large family of proteins that
      recruit and activate leukocytes, giving chemokines a major role in both immune
      response and inflammation-related diseases. The poxvirus-encoded viral CC
      chemokine inhibitor (vCCI) binds to many CC chemokines with high affinity, acting
      as a potent inhibitor of chemokine action. We have used heteronuclear
      multidimensional NMR to determine the structure of an orthopoxvirus vCCI in
      complex with a human CC chemokine, MIP-1beta (macrophage inflammatory protein
      1beta). vCCI binds to the chemokine with 1:1 stoichiometry, forming a complex of
      311 aa. vCCI uses residues from its beta-sheet II to interact with a surface of
      MIP-1beta that includes residues adjacent to its N terminus, as well as residues
      in the 20's region and the 40's loop. This structure reveals the strategy used by
      vCCI to tightly bind numerous chemokines while retaining selectivity for the CC
      chemokine subfamily.

PMID- 16963566
TI  - Small molecules that bind the inner core of gp41 and inhibit HIV envelope
      mediated fusion.
AB  - HIV-1 enters cells by membrane fusion, mediated by the trimeric viral envelope
      glycoprotein gp160, which is processed by a single proteolytic cleavage into
      stably associated gp120 and gp41. The gp120/gp41 trimer can be triggered to
      undergo an irreversible conformational change. Using a protein-based assay
      designed to mimic the gp41 conformational change, we screened for small molecules
      that prevent the formation of postfusion gp41. Several compounds were identified.
      One set of structurally related molecules inhibited formation of a postfusion
      like assembly with an IC50 of approximately 5 microM. The compounds also
      inhibited envelope-mediated membrane fusion in both cell-cell fusion and viral
      infectivity assays. Thus, our screen identifies effective fusion inhibitors.
      Tested against a panel of envelope proteins from primary HIV-1 isolates, the
      compounds inhibited fusion across a broad range of clades, including both M and T
      tropic strains. They bind in a highly conserved, hydrophobic pocket on the inner
      core of the gp41 trimer, a region previously identified as a potential inhibitor
      site.

PMID- 16963565
TI  - The effect of anticipation and the specificity of sex differences for amygdala
      and hippocampus function in emotional memory.
AB  - Prior research has shown memory is enhanced for emotional events. Key brain areas
      involved in emotional memory are the amygdala and hippocampus, which are also
      recruited during aversion and its anticipation. This study investigated whether
      anticipatory processes signaling an upcoming aversive event contribute to
      emotional memory. In an event-related functional MRI paradigm, 40 healthy
      participants viewed aversive and neutral pictures preceded by predictive warning
      cues. Participants completed a surprise recognition task directly after
      functional MRI scanning or 2 weeks later. In anticipation of aversive pictures,
      bilateral dorsal amygdala and anterior hippocampus activations were associated
      with better immediate recognition memory. Similar associations with memory were
      observed for activation of those areas in response to aversive pictures.
      Anticipatory activation predicted immediate memory over and above these
      associations for picture viewing. Bilateral ventral amygdala activations in
      response to aversive pictures predicted delayed memory only. We found that
      previously reported sex differences of memory associations with left amygdala for
      women and with right amygdala for men were confined to the ventral amygdala
      during picture viewing and delayed memory. Results support an established animal
      model elucidating the functional neuroanatomy of the amygdala and hippocampus in
      emotional memory, highlight the importance of anticipatory processes in such
      memory for aversive events, and extend neuroanatomical evidence of sex
      differences for emotional memory.

PMID- 16963567
TI  - Cytoskeletal polymer networks: the molecular structure of cross-linkers
      determines macroscopic properties.
AB  - In living cells the mechanical properties of the actin cytoskeleton are defined
      by the local activation of different actin cross-linking proteins. These proteins
      consist of actin-binding domains that are separated and geometrically organized
      by different numbers of rod domains. The detailed molecular structure of the
      cross-linking molecules determines the structural and mechanical properties of
      actin networks in vivo. In this study, we systematically investigate the impact
      of the length of the spacing unit between two actin-binding domains on in vitro
      actin networks. Such synthetic cross-linkers reveal that the shorter the
      constructs are, the greater the elastic modulus changes in the linear response
      regime. Because the same binding domains are used in all constructs, only the
      differences in the number of rod domains determine their mechanical
      effectiveness. Structural rearrangements of the networks show that bundling
      propensity is highest for the shortest construct. The nonlinear mechanical
      response is affected by the molecular structure of the cross-linker molecules,
      and the observed critical strains and fracture stress increase proportional to
      the length of the spacing unit.

PMID- 16963568
TI  - Critical residues and novel effects of overexpression of the Streptomyces
      coelicolor developmental protein BldB: evidence for a critical interacting
      partner.
AB  - The bldB gene of Streptomyces coelicolor encodes the best-characterized member of
      a family of small proteins that have low isoelectric points but that lack any
      previously characterized sequence motifs. BldB is dimeric and is required for the
      efficient production of antibiotics and spore-forming cells, called aerial
      hyphae, by growing colonies. The mechanism of action of BldB and its relatives is
      unknown. Here, we have explored amino acids in BldB that either are highly
      conserved or have been implicated in function genetically. We show that five
      amino acids are important for its function at physiological expression levels.
      Mutations in three of these amino acids gave rise to proteins that were either
      monomeric or unstable in vivo, while two others are not. We find that
      overexpression of bldB in S. coelicolor blocks sporulation prior to sporulation
      specific septation but permits the formation of aerial hyphae. Vegetative
      septation was apparently normal in both the bldB null mutant and the bldB
      overexpression strain. To our surprise, overexpression of the dimerization
      competent but functionally defective alleles caused a dramatic acceleration of
      sporulation. Our results suggest that BldB makes at least one important contact
      with another subcellular constituent and that a loss or alteration of this
      interaction impairs the phenotypic properties of the organism.

PMID- 16963570
TI  - High-molecular-weight complexes of RsbR and paralogues in the environmental
      signaling pathway of Bacillus subtilis.
AB  - Bacillus subtilis has developed an intricate signal transduction cascade to
      respond to the imposition of a variety of stresses on the cell. Reversible
      protein phosphorylation and the formation of alternative protein-protein
      complexes modulate the activity of sigma(B), the RNA polymerase sigma factor
      subunit responsible for the transcription of the general stress response genes.
      Some of the regulators of sigma(B), such as RsbR and RsbS, are known to associate
      in a 25S complex, called the stressosome, that can bind RsbT until RsbT
      phosphorylates target residues in RsbR and RsbS. To date, the RsbR-RsbS complex
      appears to be the most upstream component of the sigma(B) regulatory pathway.
      This large structure is thought to play an important role in sensing and/or
      integrating signals from different physical stresses. The roles of the paralogues
      of RsbR that are found in B. subtilis remain unclear. We describe here how the
      RsbR paralogues copurify with RsbR from B. subtilis cell lysates, and we
      demonstrate in vitro that the paralogues form large complexes either with RsbS or
      with a prepurified RsbR-RsbS binary complex. We conclude from these biochemical
      studies that stressosomes in B. subtilis cells contain minimally RsbS and all of
      the RsbT-phosphorylatable RsbR paralogues.

PMID- 16963569
TI  - C-terminal WxL domain mediates cell wall binding in Enterococcus faecalis and
      other gram-positive bacteria.
AB  - Analysis of the genome sequence of Enterococcus faecalis clinical isolate V583
      revealed novel genes encoding surface proteins. Twenty-seven of these proteins,
      annotated as having unknown functions, possess a putative N-terminal signal
      peptide and a conserved C-terminal region characterized by a novel conserved
      domain designated WxL. Proteins having similar characteristics were also detected
      in other low-G+C-content gram-positive bacteria. We hypothesized that the WxL
      region might be a determinant of bacterial cell location. This hypothesis was
      tested by generating protein fusions between the C-terminal regions of two WxL
      proteins in E. faecalis and a nuclease reporter protein. We demonstrated that the
      C-terminal regions of both proteins conferred a cell surface localization to the
      reporter fusions in E. faecalis. This localization was eliminated by introducing
      specific deletions into the domains. Interestingly, exogenously added protein
      fusions displayed binding to whole cells of various gram-positive bacteria. We
      also showed that the peptidoglycan was a binding ligand for WxL domain attachment
      to the cell surface and that neither proteins nor carbohydrates were necessary
      for binding. Based on our findings, we propose that the WxL region is a novel
      cell wall binding domain in E. faecalis and other gram-positive bacteria.

PMID- 16963571
TI  - Cooperative and critical roles for both G domains in the GTPase activity and
      cellular function of ribosome-associated Escherichia coli EngA.
AB  - To probe the cellular phenotype and biochemical function associated with the G
      domains of Escherichia coli EngA (YfgK, Der), mutations were created in the
      phosphate binding loop of each. Neither an S16A nor an S217A variant of G domain
      1 or 2, respectively, was able to support growth of an engA conditional null.
      Polysome profiles of EngA-depleted cells were significantly altered, and His(6)
      EngA was found to cofractionate with the 50S ribosomal subunit. The variants were
      unable to complement the abnormal polysome profile and were furthermore
      significantly impacted with respect to in vitro GTPase activity. Together, these
      observations suggest that the G domains have a cooperative function in ribosome
      stability and/or biogenesis.

PMID- 16963572
TI  - A conserved tetranucleotide repeat is necessary for wild-type expression of the
      Moraxella catarrhalis UspA2 protein.
AB  - The UspA2 protein has been shown to be directly involved in the serum-resistant
      phenotype of Moraxella catarrhalis. The predicted 5'-untranslated regions (UTR)
      of the uspA2 genes in several different M. catarrhalis strains were shown to
      contain various numbers (i.e., 6 to 23) of a heteropolymeric tetranucleotide
      (AGAT) repeat. Deletion of the AGAT repeats from the uspA2 genes in the serum
      resistant M. catarrhalis strains O35E and O12E resulted in a drastic reduction in
      UspA2 protein expression and serum resistance. PCR and transformation were used
      to construct a series of M. catarrhalis O12E strains that differed only in the
      number of AGAT repeats in their uspA2 genes. Expression of UspA2 was maximal in
      the presence of 18 AGAT repeats, although serum resistance attained wild-type
      levels in the presence of as few as nine AGAT repeats. Increased UspA2 expression
      was correlated with both increased binding of vitronectin and decreased binding
      of polymerized C9. Real-time reverse transcription-PCR analysis showed that
      changes in the number of AGAT repeats affected the levels of uspA2 mRNA, with 15
      to 18 AGAT repeats yielding maximal levels. Primer extension analysis indicated
      that these AGAT repeats were contained in the 5'-UTR of the uspA2 gene. The mRNA
      transcribed from a uspA2 gene containing 18 AGAT repeats was found to have a
      longer half-life than that transcribed from a uspA2 gene lacking AGAT repeats.
      These data confirm that the presence of the AGAT repeats in the 5'-UTR of the
      uspA2 gene is necessary for both normal expression of the UspA2 protein and serum
      resistance.

PMID- 16963573
TI  - Structural organization and functional properties of miniature DNA insertion
      sequences in yersiniae.
AB  - YPALs (Yersinia palindromic sequences) are miniature DNA insertions scattered
      along the chromosomes of yersiniae. The spread of these intergenic repeats likely
      occurred via transposition, as suggested by the presence of target site
      duplications at their termini and the identification of syntenic chromosomal
      regions which differ in the presence/absence of YPAL DNA among Yersinia strains.
      YPALs tend to be inserted closely downstream from the stop codon of flanking
      genes, and many YPAL targets overlap rho-independent transcriptional terminator
      like sequences. This peculiar pattern of insertion supports the hypothesis that
      most of these repeats are cotranscribed with upstream sequences into mRNAs. YPAL
      RNAs fold into stable hairpins which may modulate mRNA decay. Accordingly, we
      found that YPAL-positive transcripts accumulate in Yersinia enterocolitica cells
      at significantly higher levels than homologous transcripts lacking YPAL sequences
      in their 3' untranslated region.

PMID- 16963574
TI  - Design of a seven-genome Escherichia coli microarray for comparative genomic
      profiling.
AB  - We describe the design and evaluate the use of a high-density oligonucleotide
      microarray covering seven sequenced Escherichia coli genomes in addition to
      several sequenced E. coli plasmids, bacteriophages, pathogenicity islands, and
      virulence genes. Its utility is demonstrated for comparative genomic profiling of
      two unsequenced strains, O175:H16 D1 and O157:H7 3538 (Deltastx(2)::cat) as well
      as two well-known control strains, K-12 W3110 and O157:H7 EDL933. By using
      fluorescently labeled genomic DNA to query the microarrays and subsequently
      analyze common virulence genes and phage elements and perform whole-genome
      comparisons, we observed that O175:H16 D1 is a K-12-like strain and confirmed
      that its phi3538 (Deltastx(2)::cat) phage element originated from the E. coli
      3538 (Deltastx(2)::cat) strain, with which it shares a substantial proportion of
      phage elements. Moreover, a number of genes involved in DNA transfer and
      recombination was identified in both new strains, providing a likely explanation
      for their capability to transfer phi3538 (Deltastx(2)::cat) between them.
      Analyses of control samples demonstrated that results using our custom-designed
      microarray were representative of the true biology, e.g., by confirming the
      presence of all known chromosomal phage elements as well as 98.8 and 97.7% of
      queried chromosomal genes for the two control strains. Finally, we demonstrate
      that use of spatial information, in terms of the physical chromosomal locations
      of probes, improves the analysis.

PMID- 16963575
TI  - Unraveling the regulatory network in Streptococcus pyogenes: the global response
      regulator CovR represses rivR directly.
AB  - The response regulator CovR acts as a master regulator of virulence in
      Streptococcus pyogenes by repressing transcription of approximately 15% of the
      group A streptococcus genome directly or indirectly. We demonstrate that
      phosphorylated CovR represses transcription of rivR directly by binding to
      conserved sequences located downstream from the promoter to block procession of
      RNA polymerase. This establishes the first link in a regulatory network where
      CovR interacts directly with other proteins that modulate gene expression.

PMID- 16963576
TI  - Bile-induced curing of the virulence plasmid in Salmonella enterica serovar
      Typhimurium.
AB  - Exposure to bile induces curing of the virulence plasmid in Salmonella enterica
      serovar Typhimurium (pSLT). Disruption of the ccdB gene increases pSLT curing,
      both spontaneous and induced by bile, suggesting that the pSLT ccdAB genes may
      encode a homolog of the CcdAB addiction module previously described in the F sex
      factor. Unlike the F sex factor, synthesis of pSLT-encoded pili does not confer
      bile sensitivity. These observations may provide insights into the evolution of
      virulence plasmids in Salmonella subspecies I, as well as the causes of virulence
      plasmid loss in other Salmonella subspecies.

PMID- 16963577
TI  - Two chemosensory operons of Rhodobacter sphaeroides are regulated independently
      by sigma 28 and sigma 54.
AB  - Rhodobacter sphaeroides has a complex chemosensory system, with several loci
      encoding multiple homologues of the components required for chemosensing in
      Escherichia coli. The operons cheOp2 and cheOp3 each encode complete pathways,
      and both are essential for chemosensing. The components of cheOp2 are
      predominantly localized to the cell pole, whereas those encoded by cheOp3 are
      predominantly targeted to a discrete cluster in the cytoplasm. Here we show that
      the expression of the two pathways is regulated independently. Overlapping
      promoters recognized by sigma(28) and sigma(70) RNAP holoenzyme transcribe
      cheOp2, whereas cheOp3 is regulated by one of the four sigma(54) homologues,
      RpoN3. The different regulation of these operons may reflect the need for
      balancing responses to extra- and intracellular signals under different growth
      conditions.

PMID- 16963579
TI  - Bipolar disorder: imaging state versus trait.

PMID- 16963578
TI  - New insights into the glycosylation of the surface layer protein SgsE from
      Geobacillus stearothermophilus NRS 2004/3a.
AB  - The surface of Geobacillus stearothermophilus NRS 2004/3a cells is covered by an
      oblique surface layer (S-layer) composed of glycoprotein subunits. To this S
      layer glycoprotein, elongated glycan chains are attached that are composed of [-
      >2)-alpha-l-Rhap-(1-->3)-beta-l-Rhap-(1-->2)-alpha-L-Rhap-(1-->] repeating units,
      with a 2-O-methyl modification of the terminal trisaccharide at the nonreducing
      end of the glycan chain and a core saccharide as linker to the S-layer protein.
      On sodium dodecyl sulfate-polyacrylamide gels, four bands appear, of which three
      represent glycosylated S-layer proteins. In the present study, nanoelectrospray
      ionization time-of-flight mass spectrometry (MS) and infrared matrix-assisted
      laser desorption/ionization orthogonal time-of-flight mass spectrometry were
      adapted for analysis of this high-molecular-mass and water-insoluble S-layer
      glycoprotein to refine insights into its glycosylation pattern. This is a
      prerequisite for artificial fine-tuning of S-layer glycans for
      nanobiotechnological applications. Optimized MS techniques allowed (i)
      determination of the average masses of three glycoprotein species to be 101.66
      kDa, 108.68 kDa, and 115.73 kDa, (ii) assignment of nanoheterogeneity to the S
      layer glycans, with the most prevalent variation between 12 and 18 trisaccharide
      repeating units, and the possibility of extension of the already-known -->3)
      alpha-l-Rhap-(1-->3)-alpha-l-Rhap-(1--> core by one additional rhamnose residue,
      and (iii) identification of a third glycosylation site on the S-layer protein, at
      position threonine-590, in addition to the known sites threonine-620 and serine
      794. The current interpretation of the S-layer glycoprotein banding pattern is
      that in the 101.66-kDa glycoprotein species only one glycosylation site is
      occupied, in the 108.68-kDa glycoprotein species two glycosylation sites are
      occupied, and in the 115.73-kDa glycoprotein species three glycosylation sites
      are occupied, while the 94.46-kDa band represents nonglycosylated S-layer
      protein.

PMID- 16963580
TI  - Neurodevelopmental pathways to aggression: a model to understand and target
      treatment in youth.
AB  - The authors describe a neurodevelopmentally relevant, clinically derived model
      for understanding and treating aggressive behavior in youth. Based on case
      experience and literature review, the authors divide aggressive behavior into
      five symptomatic domains with respective neurobiological/neurodevelopmental
      underpinnings. These five symptom domains (impulsivity, affective instability,
      anxious/hyperarousal, cognitive disorganization, and predatory aggression) emerge
      as logical and clinically useful targets for treatment. The authors aim to
      establish a relationship between these symptom domains and brain structure and
      function that offers a clinically relevant approach to the complexities of
      understanding aggression and its treatment.

PMID- 16963581
TI  - Brain neuroimaging in cannabis use: a review.
AB  - In this study, the authors systematically reviewed structural and functional
      neuroimaging studies of cannabis use. Structural abnormalities generally have not
      been identified with chronic use. Regular users demonstrate reciprocal changes in
      brain activity globally and in cerebellar and frontal regions. Abstinence results
      in decreases, and administration results in increases correlating with subjective
      intoxication. Chronic use and cannabis administration result in attenuated brain
      activity in task-activated regions or activation of compensatory regions.
      Findings correlate partially with neuropsychological data, but generalization is
      limited by the lack of use of diagnostic criteria, appropriately paired
      neuropsychological testing or means to better quantify cannabis use and
      abstinence.

PMID- 16963582
TI  - Neuropsychological and neurobehavioral correlates of aggression following
      traumatic brain injury.
AB  - This study aimed to establish the neuropsychological and neurobehavioral profile
      of individuals who develop aggression following traumatic brain injury. In a
      prospective cohort study, 134 brain-injured individuals who exhibited aggression
      were compared to 153 individuals who had sustained comparable injuries but were
      not aggressive. In the aggressive group, specific deficits were identified in
      verbal memory and visuo-perceptual skills. Compared to normative data, this group
      had impaired executive-attention function. It is tentatively suggested that
      significant impairment in verbal memory and visuospatial abilities against a
      background of diminished executive-attention functioning is associated with the
      development of aggression after brain injury, especially when other risk factors
      such as low premorbid IQ, low socioeconomic status, and male gender are present.

PMID- 16963583
TI  - Abnormalities in motor physiology in bipolar disorder.
AB  - The primary purpose of this study was to examine motor physiology disturbances in
      a group of patients with bipolar disorder by using sensitive instrumental
      procedures. The secondary aim of the study was to examine the effects of the
      affective state on motor functions. The authors studied 67 individuals meeting
      DSM-IV criteria for bipolar disorder and 47 healthy comparison subjects.
      Electromechanical measures of force steadiness and scaling of movement velocity
      to distance were performed. The authors found that performance on the force
      steadiness and velocity scaling measures was significantly poorer in the subjects
      with bipolar disorder, with 58% and 63% of the patients scoring outside the
      normal range on the force steadiness and velocity scaling measures, respectively.
      Eighty-four percent of subjects showed impairment on either measure, and 37%
      showed impairment on both measures. The force steadiness and velocity scaling
      abnormalities appeared to occur independently of one another and also were not
      associated with affective state or current medication status. This study
      demonstrates that motor abnormalities suggestive of basal ganglia dysfunction
      occur in many patients with bipolar disorder.

PMID- 16963584
TI  - Mexican-American ethnicity and cognitive function: findings from an elderly
      southwestern sample.
AB  - Relatively little is known about late-life patterns of cognitive function among
      Hispanics of Mexican heritage who reside in the United States. The authors
      designed a study to assess the association between Mexican-American ethnicity
      (defined in terms of childhood and adolescent developmental history) and
      cognitive function among elderly Mexican-American and non-Hispanic white
      residents of El Paso County, Texas. Our findings indicate significant
      associations between the degree of Mexican-American ethnicity and cognitive
      impairment on all three measures of cognitive function. These statistically
      significant findings remain after effects of education, age, and gender have been
      removed from the multiple regression equation. The authors conclude that a
      dependable and clinically meaningful negative association exists between Mexican
      American ethnicity and late-life cognitive function in this region that is
      mediated by as yet unmeasured variables.

PMID- 16963585
TI  - Cognitive predictors of response to treatment for depression in multiple
      sclerosis.
AB  - Cognitive impairment, particularly in the domain of executive functioning, has
      been demonstrated to predict poorer antidepressant medication treatment response.
      In this investigation, neuropsychological functioning was evaluated as a
      predictor of depression treatment response among 59 patients with multiple
      sclerosis. Performance on a Stroop task accounted for 28.7% of the variance in
      poorer pharmacologic antidepressant treatment response, as compared to less than
      1% of the variance in two psychotherapy conditions. These results provide
      preliminary evidence to suggest that performance on neuropsychological measures
      may predict antidepressant treatment response in multiple sclerosis.

PMID- 16963586
TI  - Internal capsule size in good-outcome and poor-outcome schizophrenia.
AB  - Converging lines of research suggest that white matter abnormalities may be
      central to the pathophysiology of schizophrenia. The purpose of this study was to
      examine regional white matter in the anterior limb of the internal capsules in
      patients with schizophrenia. The authors obtained high-resolution magnetic
      resonance imaging in 106 patients with schizophrenia and 42 age and sex-matched
      healthy comparison subjects. The area of the anterior limb of the internal
      capsule was measured at five proportionately spaced dorsal-to-ventral levels.
      Schizophrenia patients were divided into good-outcome and poor-outcome groups,
      based on longitudinal analysis of self-care deficits. Patients with poor-outcome
      had significantly smaller dorsal areas than healthy comparison subjects, but good
      outcome patients did not differ from healthy comparison subjects. Larger relative
      volumes of the caudate, putamen, and thalamus tended to be associated with
      relatively larger volumes of the internal capsule in healthy comparison subjects
      and good-outcome patients, consistent with the known frontal-striatal-thalamic
      pathways. Larger ventricles were associated with smaller internal capsules,
      particularly in healthy comparison subjects. The findings suggest disruption of
      internal capsule fibers in poor-outcome patients with schizophrenia. These
      abnormalities may be independent of other structural changes in schizophrenia.

PMID- 16963587
TI  - Escitalopram for major depression in Parkinson's disease: an open-label, flexible
      dosage study.
AB  - Depression and antidepressant use are common in Parkinson's disease, but the
      benefit of selective serotonin reuptake inhibitor (SSRI) treatment in this
      population has not been established. The authors treated 14 Parkinson's disease
      patients with major depression with escitalopram in an open-label study. Although
      treatment was well tolerated and correlated with a significant decrease in
      Inventory of Depressive Symptomatology score, response and remission rates were
      only 21% and 14%, respectively. However, half of the subjects met Clinical Global
      Impression-Improvement criteria for response. In Parkinson's disease, either
      SSRIs may have limited antidepressant effects, or the use of existing depression
      diagnostic and rating instruments may be problematic.

PMID- 16963588
TI  - Predictors of subjective memory complaint in cognitively normal relatives of
      patients with Alzheimer's disease.
AB  - The authors utilized a family-based, case-control study to identify factors
      predicting subjective memory complaint in relatives of Alzheimer's disease
      patients. The authors ascertained 1,499 cognitively healthy relatives of
      Alzheimer's disease patients at 15 centers, who contributed demographic and
      medical information, including self-assessment of memory. First-degree relatives
      of Alzheimer's disease patients reported subjective memory complaint more than
      spouses of Alzheimer's disease patients. Relatives with past depression symptoms
      endorsed subjective memory complaint more than those without such history.
      Clinicians counseling family members of Alzheimer's disease patients who express
      subjective memory complaint should first evaluate cognition. If cognition is
      intact, depression should be considered.

PMID- 16963589
TI  - Unirhinal olfactory function in schizophrenia patients and first-degree
      relatives.
AB  - Previous studies report birhinal impairments in odor identification in patients
      with schizophrenia and their family members. The authors employed unirhinal odor
      identification and detection threshold sensitivity tests in schizophrenia
      patients, healthy first-degree family members, and healthy comparison subjects.
      Patients and family members showed deficits in odor identification performance in
      both nostrils. Odor detection thresholds differed only between patients and
      healthy comparison subjects. Comparable odor identification deficits in both
      patients and healthy family members suggest that odor identification measures may
      serve as a sensitive endophenotypic vulnerability marker and that unirhinal
      olfactory measures are as precise, if not more so, than birhinal performance
      measures.

PMID- 16963590
TI  - Differential effects of L-dopa and subthalamic stimulation on depressive symptoms
      and hedonic tone in Parkinson's disease.
AB  - Patients with Parkinson's disease frequently have mild to moderate depression and
      exhibit low hedonic tone. The authors investigate the impact of a single L-dopa
      challenge and the acute effects of electric stimulation of the subthalamic
      nucleus (STN) on symptoms of depression and hedonic tone. Depressive symptoms
      improved with L-dopa and STN stimulation to the same extent. However, hedonic
      tone improved only with L-dopa. Most of the emotional changes did not correlate
      with changes in motor performance, indicating they were not just reactive but
      specific to the treatment. These results demonstrate a single dissociation of
      depressive symptoms and anhedonia in response to an acute L-dopa and STN
      stimulation challenge.

PMID- 16963591
TI  - Preliminary FMRI evidence of visual system dysfunction in Parkinson's disease
      patients with visual hallucinations.
AB  - Using functional magnetic resonance imaging (fMRI), the authors examined visual
      cortex function in Parkinson's disease patients who did and did not experience
      visual hallucinations. Patients with visual hallucinations demonstrated increased
      activation in the visual association cortex and deficits in the primary visual
      cortex, suggesting that visual hallucinations are associated with an abnormality
      of visual-cortex function.

PMID- 16963592
TI  - Obsessive-compulsive symptoms in heart disease patients with and without history
      of rheumatic fever.
AB  - By comparing 51 heart disease patients with history of rheumatic fever and 46
      heart disease patients with no rheumatic fever history, the authors found a
      higher prevalence of obsessive-compulsive symptoms in rheumatic fever subjects.
      This suggests that rheumatic fever activity is not a necessary condition for the
      expression of neuropsychiatric symptoms.

PMID- 16963593
TI  - Mid-latency auditory-evoked responses and sensory gating in focal epilepsy: a
      preliminary exploration.
AB  - The relationship between epilepsy and psychosis is not well defined. Sensory
      gating is a possible endophenotype for psychosis, and has not been fully examined
      in epileptic patients. The authors examined 29 patients with focal epilepsy who
      were on antiepileptic medications, and 29 age-matched healthy comparison
      subjects, using a paired-stimulus (S1-S2) paradigm. P50 and N100 amplitudes or
      gating did not differ between the groups. The P200 was significantly smaller and
      did not gate as well in epileptic patients. Though alteration of sensory gating
      can be demonstrated in epileptic patients, it seems to be qualitatively different
      from alterations reported in association with schizophrenia.

PMID- 16963594
TI  - Motor response inhibition in children with Tourette's disorder.
AB  - Tourette's disorder has long been regarded as a disorder of involuntary movement.
      Here the authors show that children with Tourette's disorder do not differ from
      healthy comparison subjects in stop-signal inhibition. These results suggest the
      importance of considering motor tics as voluntary rather than as involuntary.

PMID- 16963595
TI  - Depressive and memory symptoms as presenting features of spinocerebellar ataxia.
AB  - The spinocerebellar ataxias (SCA) can be manifested in neuropsychiatric symptoms.
      Among 76 SCA patients presenting to a university ataxia center, depressive
      symptoms characterized SCA3. Memory symptoms occurred across all SCA groups with
      relative sparing of SCA6. These differences in neuropsychiatric symptoms suggest
      the subtype of SCA and the corresponding neuropathological involvement.

PMID- 16963596
TI  - Isolated oculogyric crisis on clozapine discontinuation.

PMID- 16963597
TI  - A case of difficult diagnosis of rabies in the absence of a dog bite in a patient
      with depression.

PMID- 16963598
TI  - Tardive dystonia-associated prescription of aripiprazole.

PMID- 16963599
TI  - Neuroacanthocytosis: presenting with depression.

PMID- 16963600
TI  - Myasthenia gravis disclosed by lithium carbonate.

PMID- 16963601
TI  - When is being known or adored by romantic partners most beneficial? Self
      perceptions, relationship length, and responses to partner's verifying and
      enhancing appraisals.
AB  - An experiment tested the hypothesis that relationship length moderates
      preferences for both verifying and enhancing appraisals from romantic partners,
      particularly for people with negative self-perceptions. One hundred and three
      romantically involved couples participated in this research. Participants with
      both negative and positive self-perceptions were randomly assigned to receive
      either verifying or enhancing feedback ostensibly created through comparison of
      their self-ratings and their partner's appraisals. The critical test was for
      those with negative self-ratings who received verifying feedback. For these
      participants, results revealed that those in longer relationships felt their
      partners were seeing the best in them more than did those in shorter
      relationships, whereas the opposite pattern of results was observed for those who
      were enhanced. Individuals with negative self-ratings who were verified also
      reported greater feelings of intimacy in the relationship when in long-term
      relationships. The importance of relationship length in moderating responses to
      partner's appraisals is discussed.

PMID- 16963602
TI  - Why do I hate thee? Conflict misperceptions and intergroup mistrust.
AB  - Members of partisan social groups often exaggerate how much their own opinions
      differ from those of their rivals. In the present two studies, partisans
      estimated their own and their rivals' attitudes toward different issues related
      to the social conflict and also made a variety of evaluative judgments about
      their own and the rival group. The authors found that (a) partisans perceive more
      disagreement with their rivals about values that are central to their own sides'
      ideological position than those that are central to their rivals' position and
      (b) perceptions of disagreement about the partisans' own central values are what
      predicts partisans' global evaluations of members of the outgroup (e.g.,
      disliking, trait stereotypes, perceived similarity). Furthermore, partisans
      believed their adversaries were motivated by an opposition to the partisans' own
      core values rather than by promotion of the adversaries' core values. Discussion
      concentrates on the theoretical and applied implications of these findings.

PMID- 16963603
TI  - When sanctions fail to increase cooperation in social dilemmas: considering the
      presence of an alternative option to defect.
AB  - Previous social dilemma research has shown that sanctioning defection may enhance
      cooperation. The authors argue that this finding may have resulted from
      restricting participants to two behaviors (cooperation and defection). In this
      article, the authors introduce the concept of a "social trilemma" (a social
      dilemma in which an alternative option to defect is present) and tested the
      effect of a sanction. The authors show that a sanction only increased cooperation
      and collective interests in the traditional social dilemma. In a social trilemma,
      the sanction failed because it caused some people to choose the alternative
      option to defect. Moreover, the results indicate that this was especially the
      case when people did not expect fellow group members to cooperate. In this case,
      the sanction even worked counterproductive because it decreased collective
      interests. It is concluded that allowing individuals to consider alternative
      options to defect can reveal the potential detrimental effects of sanctioning
      systems for the collective.

PMID- 16963604
TI  - Gender differences in attitudes toward gay men and lesbians: the role of
      motivation to respond without prejudice.
AB  - Research has uncovered consistent gender differences in attitudes toward gay men,
      with women expressing less prejudice than men (Herek, 2003). Attitudes toward
      lesbians generally show a similar pattern, but to a weaker extent. The present
      work demonstrated that motivation to respond without prejudice importantly
      contributes to these divergent attitudes. Study 1 revealed that women evince
      higher internal motivation to respond without prejudice (IMS, Plant & Devine,
      1998) than do men and that this difference partially mediates the relationship
      between gender and attitudes toward gay men. The second study replicated this
      finding and demonstrated that IMS mediates the relationship between gender and
      attitudes toward lesbians. Study 2 further revealed that gender-role variables
      contribute to the observed gender differences in motivation to respond without
      prejudice. These findings provide new insights into the nature of sexual
      prejudice and for the first time point to possible antecedents of variation in
      motivation to respond without prejudice.

PMID- 16963605
TI  - Appraisal antecedents of shame and guilt: support for a theoretical model.
AB  - Four studies used experimental and correlational methods to test predictions
      about the antecedents of shame and guilt derived from an appraisal-based model of
      self-conscious emotions (Tracy & Robins, 2004). Results were consistent with the
      predicted relations between appraisals (i.e., causal attributions) and emotions.
      Specifically, (a) internal attributions were positively related to both shame and
      guilt; (b) the chronic tendency to make external attributions was positively
      related to the tendency to experience shame; and (c) internal, stable,
      uncontrollable attributions for failure were positively related to shame, whereas
      internal, unstable, controllable attributions for failure were positively related
      to guilt. Emotions and attributions were assessed using a variety of methods, so
      converging results across studies indicate the robustness of the findings and
      provide support for the theoretical model.

PMID- 16963606
TI  - Self-benefiting in the allocation of scarce resources: leader-follower effects
      and the moderating effect of social value orientations.
AB  - Previous research on the allocation of scarce resources suggests that people who
      are assigned to higher positions (e.g., leaders) are more likely to make self
      benefiting allocations than people who are assigned to lower positions (e.g.,
      followers). In this article, the authors investigated the proposition that these
      findings would be moderated by people's social value orientations. In two
      experimental studies, the authors assigned participants either to the role of
      leader or follower and assessed the participants' social value orientations. In
      agreement with predictions, the findings show that position effects are moderated
      by social value orientation. Social value orientations only affected the
      allocation behavior of the leaders: Proself leaders allocated more resources to
      themselves than did prosocial leaders. Additional analyses indicate that these
      effects are mediated by feelings of entitlement.

PMID- 16963607
TI  - Overcoming the self-promotion dilemma: interpersonal attraction and extra help as
      a consequence of who sings one's praises.
AB  - Prior research has shown that positive information presented by a third party
      shields people from the negative consequences of being perceived as self
      promoting. But in many contexts, those third parties are intermediaries with a
      financial interest in the person being promoted rather than neutral parties. In
      three experimental studies, the authors demonstrate that even when intermediaries
      are not neutral, they can be helpful for overcoming the self-promotion dilemma-
      the need to assert one's competence but not be harmed by the fact that people who
      self-promote are viewed negatively. The authors find that hiring an agent to sing
      one's praises results in more favorable perceptions of the client, which
      contributes, in turn, to a greater willingness to offer that person assistance.
      It is also shown that even when the intermediary is physically present and seen
      to be complicit with the client, the positive effects of having someone else
      speak on one's behalf persist.

PMID- 16963609
TI  - The mediating role of perceptual validation in the repentance-forgiveness
      process.
AB  - This research focuses on one potential mechanism by which repentance leads to
      forgiveness. Two studies demonstrate that repentance leads to increased
      perceptual validation (social verification that one is correct about one's
      interpretation of an event) and, ultimately, more forgiveness. Participants
      reported more perceptual validation when they received repentance than when they
      did not (Studies 1 and 2), particularly repentance that included an
      acknowledgement of the transgression and the harm done (Study 2). In addition, in
      Study 2, acknowledgement of the transgression by a third party also had a
      positive effect on forgiveness. There was evidence that perceptual validation
      mediated the repentance-forgiveness relationship. These findings suggest that
      repentance facilitates forgiveness, at least in part, because it makes victims
      feel validated.

PMID- 16963608
TI  - Automatic activation of attachment-related goals.
AB  - When people encounter threats, their attachment systems are activated and they
      become motivated to seek protection and support through proximity to their
      attachment figures. Theoretically, therefore, mental representations of
      attachment figures should be associated with goals related to attaining proximity
      and safety. The present studies explore this idea by examining the effects of a
      person's chronic attachment style and exposure to a particular attachment
      figure's name on the automatic activation of attachment-related goals. Studies 1
      and 2 examine effects of exposure to the name of a security-providing attachment
      figure on willingness to self-disclose and seek support (two behaviors related to
      gaining proximity). Study 3 examines how exposure to names of different
      relationship partners (with whom a participant has felt secure, anxious, or
      avoidant) affects the mental accessibility of attachment-related goal words.
      Taken together, the studies support the idea that mental representations of
      attachment figures are associated with attachment-related goals.

PMID- 16963610
TI  - Nice guys finish first: the competitive altruism hypothesis.
AB  - Three experimental studies examined the relationship between altruistic behavior
      and the emergence of status hierarchies within groups. In each study, group
      members were confronted with a social dilemma in which they could either benefit
      themselves or their group. Study 1 revealed that in a reputation environment when
      contributions were public, people were more altruistic. In both Studies 1 and 2,
      the most altruistic members gained the highest status in their group and were
      most frequently preferred as cooperative interaction partners. Study 3 showed
      that as the costs of altruism increase, the status rewards also increase. These
      results support the premise at the heart of competitive altruism: Individuals may
      behave altruistically for reputation reasons because selective benefits
      (associated with status) accrue to the generous.

PMID- 16963611
TI  - Action potential characterization in intact mouse heart: steady-state cycle
      length dependence and electrical restitution.
AB  - Transgenic mice have been increasingly utilized to investigate the molecular
      mechanisms of cardiac arrhythmias, yet the rate dependence of the murine action
      potential duration and the electrical restitution curve (ERC) remain undefined.
      In the present study, 21 isolated, Langendorff-perfused, and atrioventricular
      node-ablated mouse hearts were studied. Left ventricular and left atrial action
      potentials were recorded using a validated miniaturized monophasic action
      potential probe. Murine action potentials (AP) were measured at 30, 50, 70, and
      90% repolarization (APD(30)-APD(90)) during steady-state pacing and varied
      coupling intervals to determine ERCs. Murine APD showed rate adaptation as well
      as restitution properties. The ERC time course differed dramatically between
      early and late repolarization: APD(30) shortened with increasing S1-S2 intervals,
      whereas APD(90) was prolonged. When fitted with a monoexponential function,
      APD(30) reached plateau values significantly faster than APD(90) (tau = 29 +/- 2
      vs. 78 +/- 6 ms, P < 0.01, n = 12). The slope of early APD(90) restitution was
      significantly <1 (0.16 +/- 0.02). Atrial myocardium had shorter final
      repolarization and significantly faster ERCs that were shifted leftward compared
      with ventricular myocardium. Recovery kinetics of intracellular Ca(2+) transients
      recorded from isolated ventricular myocytes at 37 degrees C (tau = 93 +/- 4 ms, n
      = 18) resembled the APD(90) ERC kinetics. We conclude that mouse myocardium shows
      AP cycle length dependence and electrical restitution properties that are
      surprisingly similar to those of larger mammals and humans.

PMID- 16963612
TI  - Frequency response characteristics of cerebral blood flow autoregulation in rats.
AB  - Transfer function analysis of blood pressure and cerebral blood flow in humans
      demonstrated that cerebrovascular autoregulation operates most effectively for
      slow fluctuations in perfusion pressure, not exceeding a frequency of
      approximately 0.15 Hz. No information on the dynamic properties of
      cerebrovascular autoregulation is available in rats. Therefore, we tested the
      hypothesis that cerebrovascular autoregulation in rats is also most effective for
      slow fluctuations in perfusion pressure below 0.15 Hz. Normotensive Wistar-Kyoto
      rats (n = 10) were instrumented with catheters in the left common carotid artery
      and jugular vein and flow probes around the right internal carotid artery. During
      isoflurane anesthesia, fluctuations in cerebral perfusion pressure were elicited
      by periodically occluding the abdominal aorta at eight frequencies ranging from
      0.008 Hz to 0.5 Hz. The protocol was repeated during inhibition of myogenic
      vascular function (nifedipine, 0.25 mg/kg body wt iv). Increases in cerebral
      perfusion pressure elicited initial increases in cerebrovascular conductance and
      decreases in resistance. At low occlusion frequencies (<0.1 Hz), these initial
      responses were followed by decreases in conductance and increases in resistance
      that were abolished by nifedipine. At occlusion frequencies of 0.1 Hz and above,
      the gains of the transfer functions between pressure and blood flow and between
      pressure and resistance were equally high in the control and nifedipine trial. At
      occlusion frequencies below 0.1 Hz, the gains of the transfer functions decreased
      twice as much under control conditions than during nifedipine application. We
      conclude that dynamic autoregulation of cerebral blood flow is restricted to very
      low frequencies (<0.1 Hz) in rats.

PMID- 16963613
TI  - Cardiac dysfunction and heart failure are associated with abnormalities in the
      subcellular distribution and amounts of oligomeric muscle LIM protein.
AB  - Prolonged hemodynamic overload results in cardiac hypertrophy and failure with
      detrimental changes in myocardial gene expression and morphology. Cysteine-rich
      protein 3 or muscle LIM protein (MLP) is thought to be a mechanosensor in cardiac
      myocytes. Therefore, the subcellular location of MLP may have functional
      implications in health and disease. Our hypothesis is that MLP becomes
      mislocalized after prolonged overload, resulting in impaired mechanosensing in
      cardiac myocytes. Using the techniques of biochemical subcellular fractionation
      and immunocytochemistry, we found MLP exhibits oligomerization in the membrane
      and cytoskeleton of cultured cardiac rat neonatal myocytes. Nuclear MLP was
      always monomeric. MLP translocated to the nucleolus in response to 10% cyclic
      stretch at 1 Hz for 48 h. This was associated with a threefold increase in S6
      ribosomal protein (P < 0.01; n = 3 cultures). Adenoviral overexpression of MLP
      also resulted in a twofold increase in S6 protein, suggesting that MLP can
      activate ribosomal protein synthesis in the nucleolus. In ventricles from aortic
      banded and myocardially infarcted rat hearts, nuclear MLP increased by twofold (P
      < 0.01; n = 7) along with a significant decrease in the nonnuclear oligomeric
      fraction. The ratio of nuclear to nonnuclear MLP increased threefold in both
      groups (P < 0.01; n = 7). In failing human hearts, there was almost a complete
      loss of oligomeric MLP. Using a flag-tagged adenoviral MLP, we demonstrate that
      the COOH terminus is required for oligomerization and that this is a precursor to
      stretch sensing and subsequent nuclear translocation. Therefore, reduced
      oligomeric MLP in the costamere and cytoskeleton may contribute to impaired
      mechanosensing in heart failure.

PMID- 16963614
TI  - Altered high-energy phosphate metabolism predicts contractile dysfunction and
      subsequent ventricular remodeling in pressure-overload hypertrophy mice.
AB  - To study the role of early energetic abnormalities in the subsequent development
      of heart failure, we performed serial in vivo combined magnetic resonance imaging
      (MRI) and (31)P magnetic resonance spectroscopy (MRS) studies in mice that
      underwent pressure-overload following transverse aorta constriction (TAC). After
      3 wk of TAC, a significant increase in left ventricular (LV) mass (74 +/- 4 vs.
      140 +/- 26 mg, control vs. TAC, respectively; P < 0.000005), size [end-diastolic
      volume (EDV): 48 +/- 3 vs. 61 +/- 8 microl; P < 0.005], and contractile
      dysfunction [ejection fraction (EF): 62 +/- 4 vs. 38 +/- 10%; P < 0.000005] was
      observed, as well as depressed cardiac energetics (PCr/ATP: 2.0 +/- 0.1 vs. 1.3
      +/- 0.4, P < 0.0005) measured by combined MRI/MRS. After an additional 3 wk, LV
      mass (140 +/- 26 vs. 167 +/- 36 mg; P < 0.01) and cavity size (EDV: 61 +/- 8 vs.
      76 +/- 8 microl; P < 0.001) increased further, but there was no additional
      decline in PCr/ATP or EF. Cardiac PCr/ATP correlated inversely with end-systolic
      volume and directly with EF at 6 wk but not at 3 wk, suggesting a role of
      sustained energetic abnormalities in evolving chamber dysfunction and remodeling.
      Indeed, reduced cardiac PCr/ATP observed at 3 wk strongly correlated with changes
      in EDV that developed over the ensuing 3 wk. These data suggest that abnormal
      energetics due to pressure overload predict subsequent LV remodeling and
      dysfunction.

PMID- 16963615
TI  - Preconditioning: a paradigm shift in the biology of myocardial ischemia.
AB  - The discovery of preconditioning (PC) has arguably been the single most important
      development in the field of ischemic biology in the past 20 years. The
      significance of this phenomenon transcends cardiovascular medicine, since it is
      ubiquitously observed in virtually every tissue of the body. This article reviews
      the pathophysiology and molecular basis of myocardial PC, with particular
      emphasis on the late phase of this cardioprotective adaptation. The article also
      discusses the exploitation of late PC for the development of novel gene therapy
      strategies aimed at inducing a permanently preconditioned cardiac phenotype
      (prophylactic cardioprotection). Besides its conceptual interest, deciphering the
      mechanism of late PC has considerable therapeutic reverberations, since transfer
      of the genes that underlie late PC would be expected to emulate the salubrious
      effects of this response of the heart to stress.

PMID- 16963616
TI  - Response of mitochondrial reactive oxygen species generation to steady-state
      oxygen tension: implications for hypoxic cell signaling.
AB  - Mitochondria are proposed to play an important role in hypoxic cell signaling.
      One currently accepted signaling paradigm is that the mitochondrial generation of
      reactive oxygen species (ROS) increases in hypoxia. This is paradoxical, because
      oxygen is a substrate for ROS generation. Although the response of isolated
      mitochondrial ROS generation to [O(2)] has been examined previously, such
      investigations did not apply rigorous control over [O(2)] within the hypoxic
      signaling range. With the use of open-flow respirometry and fluorimetry, the
      current study determined the response of isolated rat liver mitochondrial ROS
      generation to defined steady-state [O(2)] as low as 0.1 microM. In mitochondria
      respiring under state 4 (quiescent) or state 3 (ATP turnover) conditions,
      decreased ROS generation was always observed at low [O(2)]. It is concluded that
      the biochemical mechanism to facilitate increased ROS generation in response to
      hypoxia in cells is not intrinsic to the mitochondrial respiratory chain alone
      but may involve other factors. The implications for hypoxic cell signaling are
      discussed.

PMID- 16963617
TI  - Autocrine/paracrine pattern of superoxide production through NAD(P)H oxidase in
      coronary arterial myocytes.
AB  - The present study tested the hypothesis that membrane-bound NAD(P)H oxidase in
      coronary arterial myocytes (CAMs) is capable of producing superoxide (O(2)(*-))
      toward extracellular space to exert an autocrine- or paracrine-like action in
      these cells. Using a high-speed wavelength-switching fluorescent microscopic
      imaging technique, we simultaneously monitored the binding of dihydroethidium
      oxidizing product to exogenous salmon testes DNA trapped outside CAMs and to
      nuclear DNA as indicators of extra- and intracellular O(2)(*-) production. It was
      found that a muscarinic agonist oxotremorine (OXO; 80 microM) increased O(2)(*-)
      levels more rapidly outside than inside CAMs. In the presence of superoxide
      dismutase (500 U/ml) plus catalase (400 U/ml) and NAD(P)H oxidase inhibitor
      diphenylene iodonium (50 microM) or apocynin (100 microM), these increases in
      extra- and intracellular O(2)(*-) levels were substantially abolished or
      attenuated. The O(2)(*-) increase outside CAMs was also confirmed by detecting
      oxidation of nitro blue tetrazolium and confocal microscopic localization of
      Matrigel-trapped OxyBURST H(2)HFF Green BSA staining around these cells. By
      electron spin resonance spectrometry, the extracellular accumulation of O(2)(*-)
      was demonstrated as a superoxide dismutase-sensitive component outside CAMs.
      Furthermore, RNA interference of NAD(P)H oxidase subunits Nox1 or p47 markedly
      blocked OXO-induced increases in both extra- and intracellular O(2)(*-) levels,
      whereas small inhibitory RNA of Nox4 only attenuated intracellular O(2)(*-)
      accumulation. These results suggest that Nox1 represents a major NAD(P)H oxidase
      isoform responsible for extracellular O(2)(*-) production. This rapid
      extracellular production of O(2)(*-) seems to be unique to OXO-induced M(1)
      receptor activation, since ANG II-induced intra- and extracellular O(2)(*-)
      increases in parallel. It is concluded that the outward production of O(2)(*-)
      via NAD(P)H oxidase in CAMs may represent an important producing pattern for its
      autocrine or paracrine actions.

PMID- 16963618
TI  - Chronic NOS inhibition actuates endothelial-mesenchymal transformation.
AB  - Chronic kidney diseases are accompanied by the accumulation of substances like
      asymmetric dimethylarginine, phenylacetic acid, homocysteine, and advanced
      glycation end products, known to either inhibit endothelial nitric oxide synthase
      (eNOS) or uncouple it, consequently limiting the amount of available nitric oxide
      (NO). Reduced bioavailability of NO induces endothelial dysfunction. An early
      loss of peritubular capillaries in tubulointerstitial fibrotic areas and injury
      to endothelial cells have been linked to progressive renal disease. Screening
      endothelial genes in cells treated with NOS inhibitors showed upregulation of
      collagen XVIII, a precursor of a potent antiangiogenic substance, endostatin.
      This finding was confirmed at the level of mRNA and protein expression. Tie-2
      promoter-driven green fluorescent protein mice treated with nonhypertensinogenic
      doses of a NOS inhibitor exhibited upregulation of collagen XVIII/endostatin and
      rarefaction of capillary profiles. This was accompanied by the increased
      expression of transforming growth factor-beta and connective tissue growth factor
      in the kidney. Occasional endothelial cells expressed both the marker of
      endothelial lineage (green fluorescent protein) and mesenchymal marker (alpha
      smooth muscle actin or calponin). In vitro studies of endothelial cells treated
      with asymmetric dimethylarginine showed decreased expression of eNOS and Flk-1
      and enhanced expression of calponin and fibronectin, additional markers of smooth
      muscle and mesenchymal cells. These cells overexpressed transforming growth
      factor-beta and connective tissue growth factor, as well as endostatin. In
      conclusion, data presented here 1) ascribe to NO deficiency in endothelial cells
      the function of a profibrotic stimulus associated with the expression of an
      antiangiogenic fragment of collagen XVIII (endostatin) and 2) provide evidence of
      endothelial-mesenchymal transdifferentiation in the course of inhibition of NOS
      by a pathophysiologically important antagonist, asymmetric dimethylarginine. Both
      mechanisms may account for microvascular rarefaction.

PMID- 16963619
TI  - Arterial pressure transfer characteristics: effects of travel time.
AB  - We investigated the quantitative contribution of all local conduit arterial,
      blood, and distal load properties to the pressure transfer function from brachial
      artery to aorta. The model was based on anatomical data, Young's modulus, wall
      viscosity, blood viscosity, and blood density. A three-element windkessel
      represented the distal arterial tree. Sensitivity analysis was performed in terms
      of frequency and magnitude of the peak of the transfer function and in terms of
      systolic, diastolic, and pulse pressure in the aorta. The root mean square error
      (RMSE) described the accuracy in wave-shape prediction. The percent change of
      these variables for a 25% alteration of each of the model parameters was
      calculated. Vessel length and diameter are found to be the most important
      parameters determining pressure transfer. Systolic and diastolic pressure changed
      <3% and RMSE <1.8 mmHg for a 25% change in vessel length and diameter. To
      investigate how arterial tapering influences the pressure transfer, a single
      uniform lossless tube was modeled. This simplification introduced only small
      errors in systolic and diastolic pressures (1% and 0%, respectively), and wave
      shape was less well described (RMSE, approximately 2.1 mmHg). Local (arm)
      vasodilation affects the transfer function little, because it has limited effect
      on the reflection coefficient. Since vessel length and diameter translate into
      travel time, this parameter can describe the transfer accurately. We suggest that
      with a, preferably, noninvasively measured travel time, an accurate
      individualized description of pressure transfer can be obtained.

PMID- 16963620
TI  - Essential role of C-Rel in nitric-oxide synthase-2 transcriptional activation:
      time-dependent control by salicylate.
AB  - To determine the role of C-Rel in nitric-oxide synthase-2 (NOS-2) transcriptional
      activation, we evaluated the effect of lipopolysaccharide and interferon-gamma
      (LPS/IFNgamma) on C-Rel DNA binding in RAW 264.7. LPS/IFNgamma-stimulated C-Rel
      binding peaked at 4 to 8 h and declined at 24 h. Transfection of cells with a C
      Rel small interfering RNA abrogated C-Rel binding at all time points.
      LPS/IFNgamma produced superoxide at 4 h, which subsided at 8 h. C-Rel binding and
      NOS-2 expression were abrogated by superoxide dismutase or apocynin at 4 h,
      suggesting a key role that superoxide plays in mediating C-Rel binding and NOS-2
      transactivation only at 4 h. We have reported previously that salicylate at 10(
      5) M inhibited LPS/IFNgamma-induced CCAAT/enhancer binding protein beta
      (C/EBPbeta) binding at 4 h but not at 8 or 24 h. A single dose of salicylate did
      not inhibit C-Rel binding at any time point. The addition of a second dose of
      salicylate 4 h before an indicated endpoint suppressed C-Rel but not C/EBPbeta or
      interferon-gamma-regulated factor-1 binding at 8 and 24 h. A single dose of
      salicylate added with LPS/IFNgamma inhibited NOS-2 expression only at 4 h.
      However, salicylate supplement inhibited NOS-2 promoter activities and mRNA and
      protein levels throughout 24 h. Signal profiling with a panel of inhibitors
      revealed time-dependent switch of signaling pathways. These results demonstrate
      temporal regulation of transactivator binding by LPS/IFNgamma via evolving
      signaling pathways. We propose that salicylate inhibits C/EBPbeta binding at 4 h
      and C-Rel binding at 8 and 24 h by targeting related kinases.

PMID- 16963621
TI  - Oral treatment with rofecoxib reduces hippocampal excitotoxic neurodegeneration.
AB  - The purpose of this study was to determine whether the selective cyclooxygenase-2
      (COX-2) inhibitor rofecoxib [4-[4-(methylsulfonyl)phenyl]-3-phenyl-2(5H)
      furanone] could effectively prevent hippocampal neuronal injury in an animal
      model of excitotoxic neurodegeneration. COX-2 protein levels increased between 3
      and 6 h, peaked at 12 h, and declined to near baseline levels 24 h after
      injection of N-methyl-d-aspartate (NMDA; 18 nmol) into the CA1 region of the left
      hippocampus. Mice that were fed ad libitum a control rodent diet for 4 days
      before and 3 days after injection of NMDA demonstrated marked neuronal loss in
      the primary cell layers of the ipsilateral CA1, CA3, and dentate gyrus (50, 30,
      and 20% cell loss, respectively). This injury was potently and dose-dependently
      reduced by feeding animals a diet standardized to deliver 15 or 30 mg/kg
      rofecoxib per day. Neurodegeneration in the CA1 region was reduced by 30.1 +/-
      5.6 and 51.5 +/- 9.0%, respectively; in the CA3 by 64.6 +/- 12.4 and 69.0 +/-
      14.1%, respectively; and in the dentate gyrus by 47.8 +/- 15.2 and 58.0 +/-
      18.2%, respectively. Moreover, rofecoxib chow slightly but significantly reduced
      injury-induced brain edema. These findings demonstrate that rofecoxib can
      ameliorate excitotoxic neuronal injury in vivo and, as such, may be a
      particularly promising pharmaceutical for the treatment of neurological diseases
      associated with overactivation of NMDA receptors.

PMID- 16963622
TI  - Inhalation of human insulin is associated with improved insulin action compared
      with subcutaneous injection and endogenous secretion in dogs.
AB  - This study compared the effects of endogenous (portal) insulin secretion versus
      peripheral insulin administration with subcutaneous or inhaled human insulin
      [INH; Exubera, insulin human (rDNA origin) inhalation powder] on glucose disposal
      in fasted dogs. In the control group, glucose was infused into the portal vein
      (Endo; n = 6). In two other groups, glucose was infused portally, whereas insulin
      was administered peripherally by inhalation (n = 13) or s.c. injection (n = 6)
      with somatostatin and basal glucagon. In the Endo group, over the first 3 h, the
      arterial insulin concentration was twice that of the peripheral groups, whereas
      hepatic sinusoidal insulin levels were half as much. Although net hepatic glucose
      uptake was greatest in the Endo group, the peripheral groups demonstrated larger
      increases in nonhepatic glucose uptake so that total glucose disposal was greater
      in the latter groups. Compared with s.c. insulin action, glucose excursions were
      smaller and shorter, and insulin action was at least twice as great after INH.
      Thus, at the glucose dose and insulin levels chosen, peripheral insulin delivery
      was associated with greater whole-body glucose disposal than endogenous (portal)
      insulin secretion. INH administration resulted in increased insulin sensitivity
      in nonhepatic but not in hepatic tissues compared with s.c. delivery.

PMID- 16963623
TI  - Inhibition of xenograft tumor growth and down-regulation of ErbB receptors by an
      antibody directed against Lewis Y antigen.
AB  - The blood group-related Lewis Y antigen is expressed on the majority of human
      cancers of epithelial origin with only limited expression on normal tissue.
      Therefore, the Lewis Y antigen represents an interesting candidate for antibody
      based treatment strategies. Previous experiments showed that the humanized Lewis
      Y-specific monoclonal antibody, IGN311, reduced ErbB-receptor-mediated
      stimulation of mitogen-activated protein kinase by altering receptor recycling.
      Here, we tested whether binding of IGN311 to growth factor receptors is relevant
      also to inhibition of tumor growth in vivo. Prolonged incubation with IGN311 of
      human tumor cell lines, which express high levels of ErbB1 (A431) or ErbB2 (SK-BR
      3), resulted in down-regulation of the receptors and inhibition of cell
      proliferation. IGN311 inhibited the growth of tumors derived from A431 cells
      xenografted in nude mice. Treatment with IGN311 was associated with a down
      regulation of ErbB1 in the excised tumor tissue. Importantly, these effects of
      IGN311 were also mimicked by the Fab fragment of IGN311. These data indicate that
      tumor cell growth inhibition by IGN311 cannot solely be accounted for by invoking
      cellular and humoral immunological mechanisms. A direct effect on signaling via
      binding to Lewis Y glycosylated growth factor receptors on tumor cells is also
      likely to contribute to the therapeutic effect of IGN311 in vivo.

PMID- 16963624
TI  - Resolution of inflammation by retrograde chemotaxis of neutrophils in transgenic
      zebrafish.
AB  - Neutrophil chemotaxis to sites of inflammation is a critical process during
      normal immune responses to tissue injury and infection and pathological immune
      responses leading to chronic inflammation. Although progress has been made in
      understanding the mechanisms that promote neutrophil recruitment to inflamed
      tissue, the mechanisms that regulate the resolution phase of the inflammatory
      response have remained relatively elusive. To define the mechanisms that regulate
      neutrophil-mediated inflammation in vivo, we have developed a novel transgenic
      zebrafish in which the neutrophils express GFP under control of the
      myeloperoxidase promoter (zMPO:GFP). Tissue injury induces a robust, inflammatory
      response, which is characterized by the rapid chemotaxis of neutrophils to the
      wound site. In vivo time-lapse imaging shows that neutrophils subsequently
      display directed retrograde chemotaxis back toward the vasculature. These
      findings implicate retrograde chemotaxis as a novel mechanism that regulates the
      resolution phase of the inflammatory response. The zMPO:GFP zebrafish provides
      unique insight into the mechanisms of neutrophil-mediated inflammation and
      thereby offers opportunities to identify new regulators of the inflammatory
      response in vivo.

PMID- 16963625
TI  - N-terminal proteolytic processing by cathepsin G converts RANTES/CCL5 and related
      analogs into a truncated 4-68 variant.
AB  - N-terminal proteolytic processing modulates the biological activity and receptor
      specificity of RANTES/CCL5. Previously, we showed that an unidentified protease
      associated with monocytes and neutrophils digests RANTES into a variant lacking
      three N-terminal residues (4-68 RANTES). This variant binds CCR5 but exhibits
      lower chemotactic and antiviral activities than unprocessed RANTES. In this
      study, we characterize cathepsin G as the enzyme responsible for this processing.
      Cell-mediated production of the 4-68 variant was abrogated by Eglin C, a
      leukocyte elastase and cathepsin G inhibitor, but not by the elastase inhibitor
      elastatinal. Further, anti-cathepsin G antibodies abrogated RANTES digestion in
      neutrophil cultures. In accordance, reagent cathepsin G specifically digested
      recombinant RANTES into the 4-68 variant. AOP-RANTES and Met-RANTES were also
      converted into the 4-68 variant upon exposure to cathepsin G or neutrophils,
      while PSC-RANTES was resistant to such cleavage. Similarly, macaque
      cervicovaginal lavage samples digested Met-RANTES and AOP-RANTES, but not PSC
      RANTES, into the 4-68 variant and this processing was also inhibited by anti
      cathepsin G antibodies. These findings suggest that cathepsin G mediates a novel
      pathway for regulating RANTES activity and may be relevant to the role of RANTES
      and its analogs in preventing HIV infection.

PMID- 16963626
TI  - A transcription factor cascade involving Fep1 and the CCAAT-binding factor Php4
      regulates gene expression in response to iron deficiency in the fission yeast
      Schizosaccharomyces pombe.
AB  - We have identified genes encoding candidate proteins involved in iron storage
      (pcl1+), the tricarboxylic acid cycle (sdh4+), and iron-sulfur cluster assembly
      (isa1+) that are negatively regulated in response to iron deprivation. Promoter
      deletion and site-directed mutagenesis permitted identification of a new cis
      regulatory element in the promoter region of the pcl1+ gene. This cis-acting
      regulatory sequence containing the pentanucleotide sequence CCAAT is responsible
      for transcriptional repression of pcl1+ under low iron supply conditions. In
      Schizosaccharomyces pombe, the CCAAT-binding factor is a heteromeric DNA-binding
      complex that contains three subunits, designated Php2, Php3, and Php5.
      Inactivation of the php2+ locus negatively affects the transcriptional competency
      of pcl1+. A fourth subunit, designated Php4, is not essential for the
      transcriptional activation of target genes under basal and iron-replete
      conditions. We demonstrate that, in response to iron-limiting conditions, Php4 is
      required for down-regulation of pcl1+, sdh4+, and isa1+ mRNA levels. In vivo
      RNase protection studies reveal that the expression of php4+ is negatively
      regulated by iron and that this regulated expression requires a functional fep1+
      gene. The results of these studies reveal that Fep1 represses php4+ expression in
      response to iron. In contrast, when iron is scarce, Fep1 becomes inactive and
      php4+ is expressed to act as a regulatory subunit of the CCAAT-binding factor
      that is required to block pcl1+, sdh4+, and isa1+ gene transcription.

PMID- 16963627
TI  - Nonsense-mediated mRNA decay mutation in Aspergillus nidulans.
AB  - An Aspergillus nidulans mutation, designated nmdA1, has been selected as a
      partial suppressor of a frameshift mutation and shown to truncate the homologue
      of the Saccharomyces cerevisiae nonsense-mediated mRNA decay (NMD) surveillance
      component Nmd2p/Upf2p. nmdA1 elevates steady-state levels of premature
      termination codon-containing transcripts, as demonstrated using mutations in
      genes encoding xanthine dehydrogenase (hxA), urate oxidase (uaZ), the
      transcription factor mediating regulation of gene expression by ambient pH
      (pacC), and a protease involved in pH signal transduction (palB). nmdA1 can also
      stabilize pre-mRNA (unspliced) and wild-type transcripts of certain genes.
      Certain premature termination codon-containing transcripts which escape NMD are
      relatively stable, a feature more in common with certain nonsense codon
      containing mammalian transcripts than with those in S. cerevisiae. As in S.
      cerevisiae, 5' nonsense codons are more effective at triggering NMD than 3'
      nonsense codons. Unlike the mammalian situation but in common with S. cerevisiae
      and other lower eukaryotes, A. nidulans is apparently impervious to the position
      of premature termination codons with respect to the 3' exon-exon junction.

PMID- 16963628
TI  - Peroxisomal fatty acid beta-oxidation is not essential for virulence of Candida
      albicans.
AB  - Phagocytic cells form the first line of defense against infections by the human
      fungal pathogen Candida albicans. Recent in vitro gene expression data suggest
      that upon phagocytosis by macrophages, C. albicans reprograms its metabolism to
      convert fatty acids into glucose by inducing the enzymes of the glyoxylate cycle
      and fatty acid beta-oxidation pathway. Here, we asked whether fatty acid beta
      oxidation, a metabolic pathway localized to peroxisomes, is essential for fungal
      virulence by constructing two C. albicans double deletion strains: a
      pex5Delta/pex5Delta mutant, which is disturbed in the import of most peroxisomal
      enzymes, and a fox2Delta/fox2Delta mutant, which lacks the second enzyme of the
      beta-oxidation pathway. Both mutant strains had strongly reduced beta-oxidation
      activity and, accordingly, were unable to grow on media with fatty acids as a
      sole carbon source. Surprisingly, only the fox2Delta/fox2Delta mutant, and not
      the pex5Delta/pex5Delta mutant, displayed strong growth defects on nonfermentable
      carbon sources other than fatty acids (e.g., acetate, ethanol, or lactate) and
      showed attenuated virulence in a mouse model for systemic candidiasis. The degree
      of virulence attenuation of the fox2Delta/fox2Delta mutant was comparable to that
      of the icl1Delta/icl1Delta mutant, which lacks a functional glyoxylate cycle and
      also fails to grow on nonfermentable carbon sources. Together, our data suggest
      that peroxisomal fatty acid beta-oxidation is not essential for virulence of C.
      albicans, implying that the attenuated virulence of the fox2Delta/fox2Delta
      mutant is largely due to a dysfunctional glyoxylate cycle.

PMID- 16963629
TI  - The Cryptococcus neoformans catalase gene family and its role in antioxidant
      defense.
AB  - In the present study, we sought to elucidate the contribution of the Cryptococcus
      neoformans catalase gene family to antioxidant defense. We employed
      bioinformatics techniques to identify four members of the C. neoformans catalase
      gene family and created mutants lacking single or multiple catalase genes. Based
      on a phylogenetic analysis, CAT1 and CAT3 encode putative spore-specific
      catalases, CAT2 encodes a putative peroxisomal catalase, and CAT4 encodes a
      putative cytosolic catalase. Only Cat1 exhibited detectable biochemical activity
      in vitro, and Cat1 activity was constitutive in the yeast form of this organism.
      Although they were predicted to be important in spores, neither CAT1 nor CAT3 was
      essential for mating or spore viability. Consistent with previous studies of
      Saccharomyces cerevisiae, the single (cat1, cat2, cat3, and cat4) and quadruple
      (cat1 cat2 cat3 cat4) catalase mutant strains exhibited no oxidative-stress
      phenotypes under conditions in which either exogenous or endogenous levels of
      reactive oxygen species were elevated. In addition, there were no significant
      differences in the mean times to mortality between groups of mice infected with
      C. neoformans catalase mutant strains (the cat1 and cat1 cat2 cat3 cat4 mutants)
      and those infected with wild-type strain H99. We conclude from the results of
      this study that C. neoformans possesses a robust antioxidant system, composed of
      functionally overlapping and compensatory components that provide protection
      against endogenous and exogenous oxidative stresses.

PMID- 16963630
TI  - ND3 and ND4L subunits of mitochondrial complex I, both nucleus encoded in
      Chlamydomonas reinhardtii, are required for activity and assembly of the enzyme.
AB  - Made of more than 40 subunits, the rotenone-sensitive NADH:ubiquinone
      oxidoreductase (complex I) is the most intricate membrane-bound enzyme of the
      mitochondrial respiratory chain. In vascular plants, fungi, and animals, at least
      seven complex I subunits (ND1, -2, -3, -4, -4L, -5, and -6; ND is NADH
      dehydrogenase) are coded by mitochondrial genes. The role of these highly
      hydrophobic subunits in the enzyme activity and assembly is still poorly
      understood. In the unicellular green alga Chlamydomonas reinhardtii, the ND3 and
      ND4L subunits are encoded in the nuclear genome, and we show here that the
      corresponding genes, called NUO3 and NUO11, respectively, display features that
      facilitate their expression and allow the proper import of the corresponding
      proteins into mitochondria. In particular, both polypeptides show lower
      hydrophobicity compared to their mitochondrion-encoded counterparts. The
      expression of the NUO3 and NUO11 genes has been suppressed by RNA interference.
      We demonstrate that the absence of ND3 or ND4L polypeptides prevents the assembly
      of the 950-kDa whole complex I and suppresses the enzyme activity. The putative
      role of hydrophobic ND subunits is discussed in relation to the structure of the
      complex I enzyme. A model for the assembly pathway of the Chlamydomonas enzyme is
      proposed.

PMID- 16963631
TI  - Metabolic-state-dependent remodeling of the transcriptome in response to anoxia
      and subsequent reoxygenation in Saccharomyces cerevisiae.
AB  - We conducted a comprehensive genomic analysis of the temporal response of yeast
      to anaerobiosis (six generations) and subsequent aerobic recovery ( approximately
      2 generations) to reveal metabolic-state (galactose versus glucose)-dependent
      differences in gene network activity and function. Analysis of variance showed
      that far fewer genes responded (raw P value of <or=10(-8)) to the O(2) shifts in
      glucose (1,603 genes) than in galactose (2,388 genes). Gene network analysis
      reveals that this difference is due largely to the failure of "stress"-activated
      networks controlled by Msn2/4, Fhl1, MCB, SCB, PAC, and RRPE to transiently
      respond to the shift to anaerobiosis in glucose as they did in galactose. After
      approximately 1 generation of anaerobiosis, the response was similar in both
      media, beginning with the deactivation of Hap1 and Hap2/3/4/5 networks involved
      in mitochondrial functions and the concomitant derepression of Rox1-regulated
      networks for carbohydrate catabolism and redox regulation and ending (>or=2
      generations) with the activation of Upc2- and Mot3-regulated networks involved in
      sterol and cell wall homeostasis. The response to reoxygenation was rapid (<5
      min) and similar in both media, dominated by Yap1 networks involved in oxidative
      stress/redox regulation and the concomitant activation of heme-regulated ones.
      Our analyses revealed extensive networks of genes subject to combinatorial
      regulation by both heme-dependent (e.g., Hap1, Hap2/3/4/5, Rox1, Mot3, and Upc2)
      and heme-independent (e.g., Yap1, Skn7, and Puf3) factors under these conditions.
      We also uncover novel functions for several cis-regulatory sites and trans-acting
      factors and define functional regulons involved in the physiological
      acclimatization to changes in oxygen availability.

PMID- 16963632
TI  - A eukaryote without catalase-containing microbodies: Neurospora crassa exhibits a
      unique cellular distribution of its four catalases.
AB  - Microbodies usually house catalase to decompose hydrogen peroxide generated
      within the organelle by the action of various oxidases. Here we have analyzed
      whether peroxisomes (i.e., catalase-containing microbodies) exist in Neurospora
      crassa. Three distinct catalase isoforms were identified by native catalase
      activity gels under various peroxisome-inducing conditions. Subcellular
      fractionation by density gradient centrifugation revealed that most of the
      spectrophotometrically measured activity was present in the light upper
      fractions, with an additional small peak coinciding with the peak fractions of
      HEX-1, the marker protein for Woronin bodies, a compartment related to the
      microbody family. However, neither in-gel assays nor monospecific antibodies
      generated against the three purified catalases detected the enzymes in any dense
      organellar fraction. Furthermore, staining of an N. crassa wild-type strain with
      3,3'-diaminobenzidine and H(2)O(2) did not lead to catalase-dependent reaction
      products within microbodies. Nonetheless, N. crassa does possess a gene (cat-4)
      whose product is most similar to the peroxisomal type of monofunctional
      catalases. This novel protein indeed exhibited catalase activity, but was not
      localized to microbodies either. We conclude that N. crassa lacks catalase
      containing peroxisomes, a characteristic that is probably restricted to a few
      filamentous fungi that produce little hydrogen peroxide within microbodies.

PMID- 16963633
TI  - The predicted G-protein-coupled receptor GPR-1 is required for female sexual
      development in the multicellular fungus Neurospora crassa.
AB  - G-protein-coupled receptors (GPCRs) control important aspects of asexual and
      sexual development in eukaryotic organisms. We have identified a predicted GPCR
      in the filamentous fungus Neurospora crassa with similarity to cyclic AMP
      receptor like GPCRs from Dictyostelium discoideum and GCR1 from Arabidopsis
      thaliana. Expression of gpr-1 is highest in female reproductive structures, and
      deletion of gpr-1 leads to defects during sexual development. Unfertilized female
      structures (protoperithecia) from Deltagpr-1 strains are weakly pigmented, small,
      and submerged in the agar. The perithecia produced after fertilization have
      deformed beaks that lack ostioles, the openings through which ascospores are
      discharged. Localization studies using a GPR-1-green fluorescent protein fusion
      protein showed that GPR-1 is targeted to female reproductive structures. Genetic
      epistasis experiments with the three Galpha genes were inconclusive due to the
      early block in mating exhibited by Deltagna-1 strains. Phenotypic analysis of
      mutants from a high-throughput N. crassa knockout project allowed identification
      of BEK-1, a homeodomain transcription factor that is a potential target of GPR-1.
      The perithecial defects of Deltabek-1 strains are similar to those of the
      Deltagpr-1 strain, and epistasis analysis indicates that bek-1 could function
      downstream of gpr-1 during postfertilization events. The effect must be
      posttranscriptional, as bek-1 transcript levels are not affected in Deltagpr-1
      strains. The lack of ostioles in Deltagpr-1 and Deltabek-1 mutants has an
      undesirable effect on the ability to spread progeny (ascospores) by the normal
      ejection mechanism and would severely compromise the fitness of these strains in
      nature.

PMID- 16963634
TI  - Evolutionary origins of the eukaryotic shikimate pathway: gene fusions,
      horizontal gene transfer, and endosymbiotic replacements.
AB  - Currently the shikimate pathway is reported as a metabolic feature of
      prokaryotes, ascomycete fungi, apicomplexans, and plants. The plant shikimate
      pathway enzymes have similarities to prokaryote homologues and are largely active
      in chloroplasts, suggesting ancestry from the plastid progenitor genome.
      Toxoplasma gondii, which also possesses an alga-derived plastid organelle,
      encodes a shikimate pathway with similarities to ascomycete genes, including a
      five-enzyme pentafunctional arom. These data suggests that the shikimate pathway
      and the pentafunctional arom either had an ancient origin in the eukaryotes or
      was conveyed by eukaryote-to-eukaryote horizontal gene transfer (HGT). We expand
      sampling and analyses of the shikimate pathway genes to include the oomycetes,
      ciliates, diatoms, basidiomycetes, zygomycetes, and the green and red algae.
      Sequencing of cDNA from Tetrahymena thermophila confirmed the presence of a
      pentafused arom, as in fungi and T. gondii. Phylogenies and taxon distribution
      suggest that the arom gene fusion event may be an ancient eukaryotic innovation.
      Conversely, the Plantae lineage (represented here by both Viridaeplantae and the
      red algae) acquired different prokaryotic genes for all seven steps of the
      shikimate pathway. Two of the phylogenies suggest a derivation of the Plantae
      genes from the cyanobacterial plastid progenitor genome, but if the full Plantae
      pathway was originally of cyanobacterial origin, then the five other shikimate
      pathway genes were obtained from a minimum of two other eubacterial genomes.
      Thus, the phylogenies demonstrate both separate HGTs and shared derived HGTs
      within the Plantae clade either by primary HGT transfer or secondarily via the
      plastid progenitor genome. The shared derived characters support the holophyly of
      the Plantae lineage and a single ancestral primary plastid endosymbiosis. Our
      analyses also pinpoints a minimum of 50 gene/domain loss events, demonstrating
      that loss and replacement events have been an important process in eukaryote
      genome evolution.

PMID- 16963635
TI  - A 60-kilodalton protein component of the counting factor complex regulates group
      size in Dictyostelium discoideum.
AB  - Much remains to be understood about how a group of cells or a tissue senses and
      regulates its size. Dictyostelium discoideum cells sense and regulate the size of
      groups and fruiting bodies using a secreted 450-kDa complex of proteins called
      counting factor (CF). Low levels of CF result in large groups, and high levels of
      CF result in small groups. We previously found three components of CF (D. A.
      Brock and R. H. Gomer, Genes Dev. 13:1960-1969, 1999; D. A. Brock, R. D. Hatton,
      D.-V. Giurgiutiu, B. Scott, R. Ammann, and R. H. Gomer, Development 129:3657
      3668, 2002; and D. A. Brock, R. D. Hatton, D.-V. Giurgiutiu, B. Scott, W. Jang,
      R. Ammann, and R. H. Gomer, Eukaryot. Cell 2:788-797, 2003). We describe here a
      fourth component, CF60. CF60 has similarity to acid phosphatases, although it has
      very little, if any, acid phosphatase activity. CF60 is secreted by starving
      cells and is lost from the 450-kDa CF when a different CF component, CF50, is
      absent. Although we were unable to obtain cells lacking CF60, decreasing CF60
      levels by antisense resulted in large groups, and overexpressing CF60 resulted in
      small groups. When added to wild-type cells, conditioned starvation medium from
      CF60 overexpressor cells as well as recombinant CF60 caused the formation of
      small groups. The ability of recombinant CF60 to decrease group size did not
      require the presence of the CF component CF45-1 or countin but did require the
      presence of CF50. Recombinant CF60 does not have acid phosphatase activity,
      indicating that the CF60 bioactivity is not due to a phosphatase activity.
      Together, the data suggest that CF60 is a component of CF, and thus this secreted
      signal has four different protein components.

PMID- 16963636
TI  - Chromosome-wide analysis of gene function by RNA interference in the african
      trypanosome.
AB  - Trypanosomatids of the order Kinetoplastida are major contributors to global
      disease and morbidity, and understanding their basic biology coupled with the
      development of new drug targets represents a critical need. Additionally,
      trypanosomes are among the more accessible divergent eukaryote experimental
      systems. The genome of Trypanosoma brucei contains 8,131 predicted open reading
      frames (ORFs), of which over half have no known homologues beyond the
      Kinetoplastida and a substantial number of others are poorly defined by in silico
      analysis. Thus, a major challenge following completion of the T. brucei genome
      sequence is to obtain functional data for all trypanosome ORFs. As T. brucei is
      more experimentally tractable than the related Trypanosoma cruzi and Leishmania
      spp. and shares >75% of their genes, functional analysis of T. brucei has the
      potential to inform a range of parasite biology. Here, we report methods for
      systematic mRNA ablation by RNA interference (RNAi) and for phenotypic analysis,
      together with online data dissemination. This represents the first systematic
      analysis of gene function in a parasitic organism. In total, 210 genes have been
      targeted in the bloodstream form parasite, representing an essentially complete
      phenotypic catalogue of chromosome I together with a validation set. Over 30% of
      the chromosome I genes generated a phenotype when targeted by RNAi; most
      commonly, this affected cell growth, viability, and/or cell cycle progression.
      RNAi against approximately 12% of ORFs was lethal, and an additional 11% had
      growth defects but retained short-term viability in culture. Although we found no
      evidence for clustering or a bias towards widely evolutionarily conserved genes
      within the essential ORF cohort, the putative chromosome I centromere is adjacent
      to a domain containing genes with no associated phenotype. Involvement of such a
      large proportion of genes in robust growth in vitro indicates that a high
      proportion of the expressed trypanosome genome is required for efficient
      propagation; many of these gene products represent potential drug targets.

PMID- 16963637
TI  - Evidence for novel pH-dependent regulation of Candida albicans Rim101, a direct
      transcriptional repressor of the cell wall beta-glycosidase Phr2.
AB  - Candida albicans is a commensal fungus of mucosal surfaces that can cause disease
      in susceptible hosts. One aspect of the success of C. albicans as both a
      commensal and a pathogen is its ability to adapt to diverse environmental
      conditions, including dramatic variations in environmental pH. The response to a
      neutral-to-alkaline pH change is controlled by the Rim101 signal transduction
      pathway. In neutral-to-alkaline environments, the zinc finger transcription
      factor Rim101 is activated by the proteolytic removal of an inhibitory C-terminal
      domain. Upon activation, Rim101 acts to induce alkaline response gene expression
      and repress acidic response gene expression. Previously, recombinant Rim101 was
      shown to directly bind to the alkaline-pH-induced gene PHR1. Here, we demonstrate
      that endogenous Rim101 also directly binds to the alkaline-pH-repressed gene
      PHR2. Furthermore, we find that of the three putative binding sites, only the 
      124 site and, to a lesser extent, the -51 site play a role in vivo. In C.
      albicans, the predicted Rim101 binding site was thought to be CCAAGAA, divergent
      from the GCCAAG site defined in Aspergillus nidulans and Saccharomyces
      cerevisiae. Our results suggest that the Rim101 binding site in C. albicans is
      GCCAAGAA, but slight variations are tolerated in a context-dependent fashion.
      Finally, our data suggest that Rim101 activity is governed not only by
      proteolytic processing but also by an additional mechanism not previously
      described.

PMID- 16963639
TI  - Symbiotic "Archaezoa" of the primitive termite Mastotermes darwiniensis still
      play a role in cellulase production.
AB  - The relictual Mastotermes darwiniensis is one of the world's most destructive
      termites. Like all phylogenetically basal termites, it possesses protozoa in its
      hindgut, which are believed to help it digest wood. L. Li, J. Frohlich, P.
      Pfeiffer, and H. Konig (Eukaryot. Cell 2:1091-1098, 2003) recently cloned the
      genes encoding cellulases from the protozoa of M. darwiniensis; however, they
      claimed that these genes are essentially inactive, not contributing significantly
      to cellulose digestion. Instead, they suggested that the protozoa sequester
      enzymes produced by the termite in its salivary glands and use these to degrade
      cellulose in the hindgut. We tested this idea by performing gel filtration of
      enzymes in extracts of the hindgut, as well as in a combination of the salivary
      glands, foregut, and midgut. Three major cellulases were found in the hindgut,
      each of which had a larger molecular size than termite-derived salivary gland
      enzymes. N-terminal amino acid sequencing of one of the hindgut-derived enzymes
      showed that it was identical to the putative amino acid sequence of one mRNA
      sequence isolated by Li et al. (Eukaryot. Cell 2:1091-1098, 2003). The overall
      activity of the hindgut cellulases was found to be of approximately equal
      magnitude to the termite-derived cellulases detected in the mixture of salivary
      gland, foregut, and midguts. Based on these results, we conclude that, contrary
      to Li et al. (Eukaryot. Cell 2:1091-1098, 2003), the hindgut protozoan fauna of
      M. darwiniensis actively produce cellulases, which play an important role in
      cellulose digestion of the host termite.

PMID- 16963638
TI  - Saccharomyces cerevisiae a-factor mutants reveal residues critical for
      processing, activity, and export.
AB  - The Saccharomyces cerevisiae mating pheromone a-factor provides a paradigm for
      understanding the biogenesis of prenylated fungal pheromones. The biogenesis of a
      factor involves multiple steps: (i) C-terminal CAAX modification (where C is
      cysteine, A is aliphatic, and X is any residue) which includes prenylation,
      proteolysis, and carboxymethylation (by Ram1p/Ram2p, Ste24p or Rce1p, and Ste14p,
      respectively); (ii) N-terminal processing, involving two sequential proteolytic
      cleavages (by Ste24p and Axl1p); and (iii) nonclassical export (by Ste6p). Once
      exported, mature a-factor interacts with the Ste3p receptor on MATalpha cells to
      stimulate mating. The a-factor biogenesis machinery is well defined, as is the
      CAAX motif that directs C-terminal modification; however, very little is known
      about the sequence determinants within a-factor required for N-terminal
      processing, activity, and export. Here we generated a large collection of a
      factor mutants and identified residues critical for the N-terminal processing
      steps mediated by Ste24p and Axl1p. We also identified mutants that fail to
      support mating but do not affect biogenesis or export, suggesting a defective
      interaction with the Ste3p receptor. Mutants significantly impaired in export
      were also found, providing evidence that the Ste6p transporter recognizes
      sequence determinants as well as CAAX modifications. We also performed a
      phenotypic analysis of the entire set of isogenic a-factor biogenesis machinery
      mutants, which revealed information about the dependency of biogenesis steps upon
      one another, and demonstrated that export by Ste6p requires the completion of all
      processing events. Overall, this comprehensive analysis will provide a useful
      framework for the study of other fungal pheromones, as well as prenylated
      metazoan proteins involved in development and aging.

PMID- 16963640
TI  - NMR structure of the enzyme GatB of the galactitol-specific phosphoenolpyruvate
      dependent phosphotransferase system and its interaction with GatA.
AB  - The phosphoenolpyruvate-dependent carbohydrate transport system (PTS) couples
      uptake with phosphorylation of a variety of carbohydrates in prokaryotes. In this
      multienzyme complex, the enzyme II (EII), a carbohydrate-specific permease, is
      constituted of two cytoplasmic domains, IIA and IIB, and a transmembrane channel
      IIC domain. Among the five families of EIIs identified in Escherichia coli, the
      galactitol-specific transporter (II(gat)) belongs to the glucitol family and is
      structurally the least well-characterized. Here, we used nuclear magnetic
      resonance (NMR) spectroscopy to solve the three-dimensional structure of the IIB
      subunit (GatB). GatB consists of a central four-stranded parallel beta-sheet
      flanked by alpha-helices on both sides; the active site cysteine of GatB is
      located at the beginning of an unstructured loop between beta1 and alpha1 that
      folds into a P-loop-like structure. This structural arrangement shows
      similarities with other IIB subunits but also with mammalian low molecular weight
      protein tyrosine phosphatases (LMW PTPase) and arsenate reductase (ArsC). An NMR
      titration was performed to identify the GatA-interacting residues.

PMID- 16963641
TI  - Structure and function of Rv0130, a conserved hypothetical protein from
      Mycobacterium tuberculosis.
AB  - A large fraction of the Mycobacterium tuberculosis genome codes for proteins of
      unknown function. We here report the structure of one of these proteins, Rv0130,
      solved to a resolution of 1.8 a. The Rv0130 monomer features a single hotdog fold
      composed of a highly curved beta-sheet on top of a long and a short alpha-helix.
      Two monomers in turn pack to form a double-hotdog-folded homodimer, similar to a
      large group of enzymes that use thiol esters as substrates. Rv0130 was found to
      contain a highly conserved R-specific hydratase motif buried deeply between the
      two monomers. Our biochemical studies show that the protein is able to hydrate a
      short trans-2-enoyl-coenzyme A moiety with a k(cat) of 1.1 x 10(2) sec(-1). The
      importance of the side chains of D40 and H45 for hydratase activity is
      demonstrated by site-directed mutagenesis. In contrast to many hotdog-folded
      proteins, a proline residue distorts the central helix of Rv0130. This distortion
      allows the creation of a long, curved tunnel, similar to the substrate-binding
      channels of long-chain eukaryotic hydratase 2 enzymes.

PMID- 16963642
TI  - Selection of allosteric beta-lactamase mutants featuring an activity regulation
      by transition metal ions.
AB  - Libraries of phage-displayed beta-lactamase mutants in which up to three loops
      have been engineered by genetic introduction of random peptide sequences or by
      randomization of the wild-type sequence have been submitted to selection
      protocols designed to find mutants in which binding of transition metal ions to
      the engineered secondary binding site leads to significant effects on the
      enzymatic activity. A double-selection protocol was applied: The phage-displayed
      libraries were first selected for transition metal ions affinity by panning on
      IMAC support, then a second selection step was applied to isolate mutants that
      have retained significant catalytic activity. The analysis of the kinetic
      properties of mutants in the presence of nickel, copper, or zinc ions allowed
      isolation of a few mutants whose activity was either enhanced or inhibited by
      factors up to three and >10, respectively, in a metal-specific manner. A
      remarkable mutant exhibiting differential allosteric regulation depending on the
      metal was found. Its activity was activated by nickel ion binding, inhibited by
      cupric ion binding, and nearly unaffected by zinc ions. These observations point
      to an interesting potential for up- or down-regulation of activity within a
      monomeric enzyme by binding to an "allosteric site" relatively remote from the
      active site.

PMID- 16963643
TI  - Active TEM-1 beta-lactamase mutants with random peptides inserted in three
      contiguous surface loops.
AB  - Engineering of alternative binding sites on the surface of an enzyme while
      preserving the enzymatic activity would offer new opportunities for controlling
      the activity by binding of non-natural ligands. Loops and turns are the natural
      substructures in which binding sites might be engineered with this purpose. We
      have genetically inserted random peptide sequences into three relatively rigid
      and contiguous loops of the TEM-1 beta-lactamase and assessed the tolerance to
      insertion by the percentage of active mutants. Our results indicate that
      tolerance to insertion could not be correlated to tolerance to mutagenesis. A
      turn between two beta-strands bordering the active site was observed to be
      tolerant to random mutagenesis but not to insertions. Two rigid loops comprising
      rather well-conserved amino acid residues tolerated insertions, although with
      some constraints. Insertions between the N-terminal helix and the first beta
      strand generated active libraries if cysteine residues were included at both ends
      of the insert, suggesting the requirement for a stabilizing disulfide bridge.
      Random sequences were relatively well accommodated within the loop connecting the
      final beta-strand to the C-terminal helix, particularly if the wild-type residue
      was retained at one of the loops' end. This suggests two strategies for
      increasing the percentage of active mutants in insertion libraries. The amino
      acid distribution in the engineered loops was analyzed and found to be less
      biased against hydrophobic residues than in natural medium-sized loops. The
      combination of these activity-selected libraries generated a huge library
      containing active hybrid enzymes with all three loops modified.

PMID- 16963644
TI  - Amyloid formation in denatured single-mutant lysozymes where residual structures
      are modulated.
AB  - Reduced hen lysozyme has a residual structure involving long-range interaction.
      It has been demonstrated that a single mutation (A9G, W62G, W111G, or W123G) in
      the residual structure differently modulates the long-range interactions of
      reduced lysozyme. To examine whether such variations in the residual structure
      affect amyloid formation, reduced and alkylated mutant lysozymes were incubated
      under the amyloid-fibrillation condition. From the analyses of CD spectra and
      thioflavine T fluorescences, it was suggested that variation in residual
      structure led to different amyloid formation. Interestingly, the extent of
      amyloid formation did not always correlate with the extent to which the residual
      structure was maintained, resulting in the involvement of a hydrophobic cluster
      normally contained in W111 in the reduced lysozyme.

PMID- 16963645
TI  - Localization of binding sites in protein structures by optimization of a
      composite scoring function.
AB  - The rise in the number of functionally uncharacterized protein structures is
      increasing the demand for structure-based methods for functional annotation.
      Here, we describe a method for predicting the location of a binding site of a
      given type on a target protein structure. The method begins by constructing a
      scoring function, followed by a Monte Carlo optimization, to find a good scoring
      patch on the protein surface. The scoring function is a weighted linear
      combination of the z-scores of various properties of protein structure and
      sequence, including amino acid residue conservation, compactness, protrusion,
      convexity, rigidity, hydrophobicity, and charge density; the weights are
      calculated from a set of previously identified instances of the binding-site type
      on known protein structures. The scoring function can easily incorporate
      different types of information useful in localization, thus increasing the
      applicability and accuracy of the approach. To test the method, 1008 known
      protein structures were split into 20 different groups according to the type of
      the bound ligand. For nonsugar ligands, such as various nucleotides, binding
      sites were correctly identified in 55%-73% of the cases. The method is completely
      automated (http://salilab.org/patcher) and can be applied on a large scale in a
      structural genomics setting.

PMID- 16963646
TI  - Oligomerization behavior of the archaeal Sm2-type protein from Archaeoglobus
      fulgidus.
AB  - As part of a functional analysis of archaeal Sm-related proteins, we have studied
      the oligomerization behavior of the Sm-2 type protein from the euryarchaeon
      Archaeoglobus fulgidus using gel filtration chromatography and noncovalent mass
      spectrometry. Our experiments show that the oligomeric state of the protein
      depends on the pH and presence of RNA. The protein forms a hexamer at acidic pH
      in the absence of RNA. The addition of RNA (oligo U10) induces the formation of a
      heptamer over the whole pH range studied. The stability of both the hexamer and
      the RNA-bound heptamer increases at lower pH.

PMID- 16963647
TI  - Design and NMR conformational study of a beta-sheet peptide based on Betanova and
      WW domains.
AB  - A good approach to test our current knowledge on formation of protein beta-sheets
      is de novo protein design. To obtain a three-stranded beta-sheet mini-protein, we
      have built a series of chimeric peptides by taking as a template a previously
      designed beta-sheet peptide, Betanova-LLM, and incorporating N- and/or C-terminal
      extensions taken from WW domains, the smallest natural beta-sheet domain that is
      stable in absence of disulfide bridges. Some Betanova-LLM strand residues were
      also substituted by those of a prototype WW domain. The designed peptides were
      cloned and expressed in Escherichia coli. The ability of the purified peptides to
      adopt beta-sheet structures was examined by circular dichroism (CD). Then, the
      peptide showing the highest beta-sheet population according to the CD spectra,
      named 3SBWW-2, was further investigated by 1H and 13C NMR. Based on NOE and
      chemical shift data, peptide 3SBWW-2 adopts a well defined three-stranded
      antiparallel beta-sheet structure with a disordered C-terminal tail. To discern
      between the contributions to beta-sheet stability of strand residues and the C
      terminal extension, the structural behavior of a control peptide with the same
      strand residues as 3SBWW-2 but lacking the C-terminal extension, named Betanova
      LYYL, was also investigated. beta-Sheet stability in these two peptides, in the
      parent Betanova-LLM and in WW-P, a prototype WW domain, decreased in the order WW
      P > 3SBWW-2 > Betanova-LYYL > Betanova-LLM. Conclusions about the contributions
      to beta-sheet stability were drawn by comparing structural properties of these
      four peptides.

PMID- 16963649
TI  - Probing protein structure and dynamics by second-derivative ultraviolet
      absorption analysis of cation-{pi} interactions.
AB  - We describe an alternate approach for studying protein structure using the
      detection of ultraviolet (UV) absorbance peak shifts of aromatic amino acid side
      chains induced by the presence of salts. The method is based on the hypothesis
      that salt cations (Li+, Na+, and Cs+) of varying sizes can differentially diffuse
      through protein matrices and interact with benzyl, phenyl, and indole groups
      through cation-pi interactions. We have investigated the potential of this method
      to probe protein dynamics by measuring high resolution second-derivative UV
      spectra as a function of salt concentration for eight proteins of varying
      physical and chemical properties and the N-acetylated C-ethyl esterified amino
      acids to represent totally exposed side chains. We show that small shifts in the
      wavelength maxima for Phe, Tyr, and Trp in the presence of high salt
      concentrations can be reliably measured and that the magnitude and direction of
      the peak shifts are influenced by several factors, including protein size,
      charge, and the local environment and solvent accessibility of the aromatic
      groups. Evaluating the empirical UV spectral data in light of known protein
      structural information shows that probing cation-pi interactions in proteins
      reveals unique information about the influence of structure on aromatic side
      chain spectroscopic behavior.

PMID- 16963648
TI  - Theoretical investigation of the photoinitiated folding of HP-36.
AB  - A computational model was developed to examine the phototriggered folding of a
      caged protein, a protein modified with an organic photolabile cross-linker.
      Molecular dynamics simulations of the modified 36-residue fragment of subdomain B
      of chicken villin head piece with a photolabile linker were performed, starting
      from both the caged and the uncaged structures. Construction of a free-energy
      landscape, based on principal components as well as on radius of gyration versus
      root-mean-square deviation, and circular dichroism calculations were employed to
      characterize folding behavior and structures. The folded structures observed in
      the molecular dynamics trajectories were found to be similar to that of the wild
      type protein, in agreement with the published experimental results. The free
      energy landscapes of the modified and wild-type proteins have similar topology,
      suggesting common thermodynamic/kinetic behavior. The existence of small
      differences in the free-energy surface of the modified protein from that of the
      native protein, however, indicates subtle differences in the folding behavior.

PMID- 16963650
TI  - Cooling the fire within: inhaled corticosteroids and cardiovascular mortality in
      COPD.

PMID- 16963651
TI  - Think of HIT when thrombosis follows heparin.

PMID- 16963652
TI  - Can you get more than you paid for with lung cancer screening?

PMID- 16963653
TI  - Bronchoscopic cytology: Expanding the menu.

PMID- 16963654
TI  - Painful lessons from the other side (of the diaphragm).

PMID- 16963655
TI  - Pulmonary practice profiles: Results of a practice performance survey.

PMID- 16963656
TI  - Paying attention to at-risk commercial vehicle operators.

PMID- 16963657
TI  - Inhaled corticosteroids and mortality in COPD.
AB  - STUDY OBJECTIVES: To assess the influence of inhaled corticosteroids (ICSs) on
      mortality in COPD patients, which is currently a controversial topic. SETTING:
      Manitoba Health maintains a population-wide research database that includes
      pharmaceutical information. DESIGN AND PATIENTS: We examined mortality in people
      90 to 365 days after hospital discharge for COPD, comparing those persons who
      received inhaled steroids within 90 days of hospital discharge with those who did
      not. Cox proportional hazards models were used with adjustments for other
      respiratory drugs, comorbidities, and physician visits before and after hospital
      discharge. We also compared mortality in patients who received inhaled steroids
      with those who received other respiratory drugs, but not inhaled steroids, and
      those who received neither. Using nested case control analysis, we examined the
      time of receipt of inhaled steroids in relation to fatal events. RESULTS: In
      people > 65 years of age, inhaled steroids were associated with a 25% reduction
      in mortality between 90 and 365 days after hospital discharge, while mortality
      increased with bronchodilator use, physician visits, age, and comorbidities. The
      exclusion of people who had also received a diagnosis of asthma or had received
      inhaled steroids before hospitalization did not change the result. Inhaled
      steroids were associated with an even larger mortality reduction in people aged
      35 to 64 years. People who received bronchodilators but no steroids had higher
      mortality than people who received no bronchodilators or received both
      bronchodilators and inhaled steroids. The reduction in all-cause mortality was
      largely due to the decreased number of cardiovascular deaths. The receipt of
      inhaled steroids within 30 days of death was protective, but this was not the
      case for greater time intervals. CONCLUSIONS: Therapy with ICSs reduced mortality
      in COPD patients; the effect was particularly notable for cardiovascular death
      and was short term in that it was dependent on recent exposure.

PMID- 16963658
TI  - Effect of fluticasone propionate/salmeterol on lung hyperinflation and exercise
      endurance in COPD.
AB  - STUDY OBJECTIVE: To examine the effect of fluticasone propionate, 250
      microg/salmeterol, 50 microg combination (FSC 250/50) twice daily on lung
      hyperinflation and associated measures of exercise performance in patients with
      COPD. DESIGN: This was a randomized, double-blind, parallel-group study.
      PATIENTS: Eligible patients were > or = 40 years old with a diagnosis of COPD,
      prealbuterol FEV(1) < 70% of predicted, FEV1/FVC ratio > or = 0.70, and
      functional residual capacity (FRC) > or = 120% of predicted normal.
      INTERVENTIONS: Patients were randomized to FSC 250/50; salmeterol, 50 microg; or
      placebo twice daily for 8 weeks. Predose and postdose spirometry,
      plethysmography, and constant-load cycle cardiopulmonary exercise test
      evaluations were compared. The primary comparison was FSC 250/50 with placebo.
      The salmeterol group was included for exploratory comparisons with FSC 250/50.
      RESULTS: A total of 185 patients (mean baseline FEV1 of 41% predicted) were
      enrolled. At rest, FSC 250/50 significantly reduced postdose FRC and increased
      inspiratory capacity (IC) compared with placebo (differences of - 0.35 +/- 0.12 L
      and 0.33 +/- 0.06 L [mean +/- SE], respectively, at week 8; p > or = 0.003) and
      increased exercise endurance time (difference, 132 +/- 45 s; p = 0.004). At a
      standardized time during exercise (isotime), FSC 250/50 increased postdose IC by
      0.20 +/- 0.05 L over placebo with associated improvements in tidal volume and
      minute ventilation (p < 0.05 vs placebo at week 8). Improvement in exercise time
      was significantly correlated with the increase in IC (r = 0.45, p < 0.001) but
      not FEV1 (r = 0.23, p = 0.08). Predose comparisons of FSC 250/50 with salmeterol
      and placebo favored FSC 250/50. CONCLUSION: We conclude that FSC 250/50 decreases
      lung hyperinflation at rest and during exercise with an associated increase in
      exercise endurance time when compared with placebo.

PMID- 16963659
TI  - Technical and functional assessment of 10 office spirometers: A multicenter
      comparative study.
AB  - STUDY OBJECTIVES: To investigate the technical properties and user friendliness
      of 10 office spirometers devoted for use in general practice, and to compare the
      results with standard diagnostic spirometers. DESIGN: Multicenter study. SETTING:
      Ten spirometer models were tested independently in three pulmonary function
      laboratories and by three general practitioners (GPs). MEASUREMENTS: The
      laboratories studied the technical quality of the office spirometers in terms of
      precision and agreement with standard spirometers, whereas the three GPs assessed
      their user friendliness. The spirometers tested were as follows: Spirobank
      (Medical International Research; Rome, Italy); Simplicity (Puritan Bennett;
      Pleasanton, CA); OneFlow (Clement Clarke International; Harlow, Essex, UK);
      Datospir 70 (Sibelmed; Barcelona, Spain); Datospir 120 (Sibelmed); SpiroPro
      (SensorMedics; Yorba Linda, CA); EasyOne (NDD; Zurich, Switzerland); MicroLoop
      (Micro Medical; Chatham, Kent, UK); SpiroStar (Medikro; Kuopio, Finland); and
      Pneumotrac (Vitalograph; Maids Moreton, Buckingham, UK). FVC and FEV1 were
      measured in 399 subjects. User friendliness was assessed by the three GPs using a
      questionnaire. RESULTS: The precision of FEV1 of the office and standard
      spirometers was comparable, but three office spirometers had > 200 mL limits of
      precision for FVC. Some devices presented a proportional difference on the FEV1
      with standard spirometers, underestimating the small values. The limits of
      agreements between standard and some office spirometers for FEV1/FVC ratio was >
      10%. The overall user friendliness was estimated as good. CONCLUSIONS: The global
      quality and user friendliness of several office spirometers make them acceptable
      for the detection of COPD, although differences between the laboratory and some
      of the office spirometers values suggest that the misclassification rates may be
      increased when using some models of office spirometers.

PMID- 16963660
TI  - Physician-diagnosed COPD global initiative for chronic obstructive lung disease
      stage IV in Ostersund, Sweden: Patient characteristics and estimated prevalence.
AB  - BACKGROUND: The prevalence of COPD is estimated to 4 to 14%. According to the
      Global Initiative for Chronic Obstructive Lung Disease guidelines, COPD is
      divided into four stages. Patients with stage IV disease (very severe) have FEV1
      < 30% of predicted values and/or respiratory insufficiency. The few studies that
      exist have reported a stage IV disease prevalence of 0.1 to 0.2% but provide
      limited additional patient characteristics. The present study estimated the
      prevalence of physician-diagnosed stage IV COPD in the city of Ostersund, Sweden,
      and characterized the patients. METHODS: Due to the regional integrated care
      pathway, patients in whom severe COPD is diagnosed are under surveillance by the
      Respiratory Department at Ostersund Hospital. Among these patients and all others
      in whom COPD has been diagnosed at Ostersund Hospital from 2000 to 2004, all
      those with an FEV1 of < 40% predicted were examined. RESULTS: A total of 76
      patients fulfilled the criteria for stage IV COPD. The mean age was 71 years, 59%
      were women, and 40% were receiving long-term oxygen therapy. Sixty-five percent
      of the patients lived independently at home, 9% were present smokers, and 75%
      used inhaled corticosteroids daily. Sixty-seven percent of the patients had
      received vaccination against influenza the previous year. During 2004, 48% of the
      patients had at least one COPD-related hospitalization, and 11% had made at least
      one visit to the hospital for emergency care. CONCLUSIONS: The present study
      indicated that 0.13% of the population in Ostersund in 2004 had physician
      diagnosed stage IV COPD. This is probably an underestimation of the true
      prevalence. Patients with stage IV COPD appear to require periods of
      hospitalization more often than intermittent emergency department visits.

PMID- 16963661
TI  - Exploring the time dependence of serum clara cell protein as a biomarker of
      pulmonary injury in humans.
AB  - We have previously demonstrated Clara cell protein (CC16) [secretoglobin 1A1] in
      serum to be a highly sensitive biomarker of altered lung epithelial permeability
      after ozone challenge. As a previous experimental study has indicated a diurnal
      variation in serum CC16 in humans, the aims of the present investigation were to
      confirm this observation and to attempt to model the diurnal variation in CC16
      concentrations. In 18 healthy nonsmoking subjects, peripheral blood samples were
      drawn at six sampling points over a 15-h period and repeated twice within 3 to 4
      weeks. A clear within-day variation was revealed in serum CC16 concentrations,
      falling significantly from baseline levels between the 11:30 am and 10:00 pm time
      points (p = 0.000). Furthermore, it was shown that this within-day variation was
      reproducible regardless of subject or day, enabling the diurnal variation in
      serum CC16 to be modeled and fitted a second-degree polynomial for the observed
      time span. In conclusion, the present data demonstrate a pronounced time
      dependent diurnal variation in serum levels of CC16, which can be mathematically
      compensated for, when addressing the issue of an air pollution-induced effect on
      CC16 in field studies.

PMID- 16963662
TI  - Long-term prognosis for patients with COPD treated in the prehospital setting: Is
      it influenced by hospital admission?
AB  - STUDY OBJECTIVES: Our aim was to assess long-term prognosis for patients with an
      exacerbation of COPD who were treated by the anesthesiologists of the Mobile
      Emergency Care Unit (MECU) of Copenhagen. We specifically sought to examine
      whether mortality was different among patients released before hospital admission
      and those admitted to the hospital. DESIGN: An observational cohort study with 5
      year follow-up. SETTING: Prehospital and university hospital. PATIENTS: Patients
      with exacerbation of COPD treated by the MECU. MEASUREMENTS: We included all
      patients treated from 2000 to 2001. In September 2005, we conducted a search to
      find out whether these patients were still alive, and we analyzed survival using
      Kaplan-Meier statistics and log-rank test. Patients admitted to the hospital
      (primarily or secondarily) were compared to patients treated and released before
      hospital admission. RESULTS: In total, 573 patients with COPD had 995 episodes of
      exacerbation treated by the MECU in the 2-year period. On September 1, 2005, only
      155 patients (27%) were alive. In 245 of the exacerbation episodes (25%) among
      163 patients, hospital admission was not necessary primarily, but in 42 of these
      exacerbations (17%), secondary admission occurred within 48 h. Mortality was
      significantly higher (p = 0.02) in patients admitted to the hospital either
      primarily or secondarily, compared to patients treated and released before
      admission to the hospital. CONCLUSIONS: Mortality was high among COPD patients.
      Less than one fifth of patients treated at home and released are admitted to
      hospital secondarily. Mortality was significantly higher among admitted patients.
      A set of criteria selecting the patient prone to secondary admission is
      desirable.

PMID- 16963663
TI  - How frequently is venous thromboembolism in heparin-treated patients associated
      with heparin-induced thrombocytopenia?
AB  - BACKGROUND: Patients receiving heparin for thromboprophylaxis or treatment may
      have new or recurrent venous thromboembolism (VTE) if immune-mediated heparin
      induced thrombocytopenia (HIT) occurs or for other reasons, eg, if
      anticoagulation fails. We estimated from the literature how frequently a patient
      presenting with VTE during or following heparin therapy has HIT-associated VTE.
      METHODS: A comprehensive, systematic literature search was conducted to identify
      studies using unfractionated or low-molecular-weight heparin (LMWH) for
      thromboprophylaxis or treatment in which new or recurrent VTE and serologically
      confirmed HIT were reported. From extracted study data, the proportion of
      patients with HIT-associated VTE relative to any VTE was calculated by heparin
      type and mode of administration. RESULTS: We identified 10 studies, some with
      multiple arms, that used unfractionated heparin (IV administration, 5 studies;
      subcutaneous administration, 3 studies) or subcutaneous LMWH (5 studies) and met
      analysis criteria. Across these studies, 386 of 6,219 heparin-treated patients
      had VTE, including 32 patients who also had HIT. The frequency of HIT-associated
      VTE among heparin-treated patients with VTE was comparable between IV and
      subcutaneous unfractionated heparin therapy (13.2% [17 of 129 patients] vs 12.4%
      [14 of 113 patients]; odds ratio, 1.07; 95% confidence interval, 0.50 to 2.3; p >
      0.99) yet significantly different between unfractionated heparin and LMWH therapy
      (12.8% [31 of 242 patients] vs 0.7% [1 of 144 patients]; odds ratio, 21.0; 95%
      confidence interval, 2.8 to 156; p < 0.001). CONCLUSIONS: VTE is associated with
      HIT infrequently (< 1%) in LMWH-treated patients, yet often (approximately one in
      eight cases) in unfractionated heparin-treated patients. Physicians should
      suspect the possibility of HIT if VTE develops during or soon after
      unfractionated heparin use; if thrombocytopenia is present, alternative
      anticoagulation should be used until HIT is excluded.

PMID- 16963664
TI  - Abnormalities on chest radiograph reported in subjects in a cancer screening
      trial.
AB  - BACKGROUND: Chest radiographs (CXRs) are commonly performed for diagnostic and
      other purposes. There is little literature either on the prevalence in the
      general population of various abnormalities seen on CXRs or on the risks
      associated with these abnormalities. METHODS: We followed up > 70,000 men and
      women who were enrolled in the Prostate, Lung, Colorectal and Ovarian Cancer
      Screening Trial. Subjects received four annual posteroanterior CXRs for the early
      detection of lung cancer. Radiologists noted the presence of non-cancer-related
      abnormalities as well as nodules/masses that were suspicious for lung cancer.
      Subjects were followed up for mortality and cancer incidence. RESULTS:
      Abnormalities that were not suspicious for lung cancer were observed on 35% of
      examinations, compared to 8% of examinations with findings that were suspicious
      for cancer. The most commonly reported noncancer abnormalities were granuloma
      (10.7% of examinations), scarring/pulmonary fibrosis (8.2% of examinations),
      bone/soft tissue lesions (5.5% of examinations), cardiac abnormalities (4.4% of
      examinations), pleural fibrosis (3.6% of examinations), and COPD/emphysema (2.5%
      of examinations). Most noncancer abnormalities were more prevalent in men, older
      subjects, and smokers. Controlling for age, smoking, and other factors,
      scarring/pulmonary fibrosis was significantly associated with an increased risk
      of lung cancer with a hazard ratio (HR) of 2.0, while cardiac abnormalities (HR,
      2.1), scarring/pulmonary fibrosis (HR, 1.4), COPD (HR, 1.7), and pleural fluid
      (HR, 2.3) were significantly associated with increased overall (ie, non-lung
      cancer) mortality. CONCLUSION: Abnormalities that are not suspicious for lung
      cancer are common in a population undergoing screening. Some of these
      abnormalities are associated with an increased risk for lung cancer incidence
      and/or overall mortality.

PMID- 16963665
TI  - A comparison of cytology and fluorescence in situ hybridization for the detection
      of lung cancer in bronchoscopic specimens.
AB  - STUDY OBJECTIVES: To determine the relative sensitivity and specificity of
      cytology and fluorescence in situ hybridization (FISH) for the detection of lung
      cancer in bronchoscopically obtained specimens. DESIGN: Cytology and FISH were
      performed on brushing and washing specimens obtained from patients undergoing
      bronchoscopy for suspected lung cancer. FISH utilized the LAVysion probe set
      (Abbott Molecular; Des Plaines, IL), which contains locus-specific probes to
      5p15, 7p12 (EGFR), 8q24 (C-MYC), and a centromeric probe to chromosome 6.
      SETTING: Single-center, academic, tertiary medical center. PARTICIPANTS: One
      hundred thirty-seven patients referred for bronchoscopy for suspicion of lung
      cancer. INTERVENTIONS: Cytology and FISH were performed on bronchoscopic
      brushings and washings. MEASUREMENTS AND RESULTS: One hundred thirty-seven
      patients undergoing bronchoscopy had pathology, FISH, and cytology results. FISH
      and cytology were performed on 123 washing and 78 brushing specimens.
      Sensitivities of FISH and cytology were 71% and 51% (p = 0.007), respectively,
      for brushing specimens, and 49% and 44% (p = 0.541) for washing specimens. When
      FISH and cytology results were combined, sensitivities were 75% and 61%,
      respectively, for brushing and washing specimens, which was significantly better
      (p < 0.001) than cytology alone. Specificities of FISH and cytology for patients
      with negative findings at the time of initial bronchoscopy were 83% and 100% (p =
      0.125), respectively, for brushing specimens, and 95% and 100% (p = 0.500) for
      washing specimens. CONCLUSIONS: These findings show that FISH is significantly
      more sensitive than conventional cytology for detecting lung cancer in bronchial
      brushing specimens; when combined with cytology, FISH can improve the diagnostic
      sensitivity of detecting malignancy in bronchial brushing and washing specimens.

PMID- 16963666
TI  - Evidence of innervation in talc-induced pleural adhesions.
AB  - STUDY OBJECTIVES: To conduct a detailed morphologic and ultrastructural study of
      pleural adhesions following talc pleurodesis. METHODS: Talc with a main particle
      size of 8.36 +/- 0.2 mum (mean +/- SEM) and at a dose of 200 mg/kg in a 2-mL
      slurry was instilled via a small catheter into the pleural cavity of 10 male
      rabbits. Five rabbits were killed at 1 week, and five rabbits were killed at 1
      month after instillation. At autopsy, after macroscopically observing the pleural
      cavity, adhesions were excised from opposing pleural surfaces and processed for
      histopathologic, immunocytochemical, and ultrastructural study. RESULTS: At 1
      week, all adhesions examined were mesothelium-covered fibrovascular bands
      containing well-developed blood and lymphatic vessels establishing a structural
      continuity between both pleural layers. Nerves were present in adhesions from 20%
      of the rabbits. They consisted of a single fascicle containing 5 to 20 thin
      myelinated axons of various diameters (1 to 6 microm) uniformly distributed
      throughout the nerve section. The anatomic location of the adhesion did not
      appear to influence its overall morphology. CONCLUSIONS: As early as at 1 week,
      adhesions are well-formed structures more resembling newly formed pleural tissue
      than a simple scar. Nerve fibers in pleural adhesions are reported for the first
      time, which suggests that these adhesions are potentially capable of conducting
      pain stimuli. Further studies are required in order to confirm our results in
      human pleural adhesions.

PMID- 16963667
TI  - Comparison of endobronchial ultrasound, positron emission tomography, and CT for
      lymph node staging of lung cancer.
AB  - STUDY OBJECTIVES: To perform a prospective comparison of direct real-time
      endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA),
      positron emission tomography (PET), and thoracic CT for detection of mediastinal
      and hilar lymph node metastasis in patients with lung cancer considered for
      surgical resection. DESIGN: Prospective patient enrollment. SETTING: University
      teaching hospital. PATIENTS: One hundred two potentially operable patients with
      proven (n = 96) or radiologically suspected (n = 6) lung cancer were included in
      the study. INTERVENTIONS: CT, PET, and EBUS-TBNA were performed prior to surgery
      for the evaluation of mediastinal and hilar lymph node metastasis. The convex
      probe EBUS, which is integrated with a convex scanning probe on its tip, was used
      for EBUS-TBNA. Surgical histology was used as the "gold standard" to confirm
      lymph node metastasis unless patients were found inoperable for N3 or extensive
      N2 disease proven by EBUS-TBNA. MAIN RESULTS: EBUS-TBNA was successfully
      performed in all 102 patients (mean age, 67.8 years) from 147 mediastinal and 53
      hilar lymph nodes. EBUS-TBNA proved malignancy in 37 lymph node stations in 24
      patients. CT identified 92 positive lymph nodes, and PET identified 89 positive
      lymph nodes (4 supraclavicular, 63 mediastinal, 22 hilar). The sensitivities of
      CT, PET, and EBUS-TBNA for the correct diagnosis of mediastinal and hilar lymph
      node staging were 76.9%, 80.0%, and 92.3%, respectively; specificities were
      55.3%, 70.1%, and 100%, and diagnostic accuracies were 60.8%, 72.5%, and 98.0%.
      EBUS-TBNA was uneventful, and there were no complications. CONCLUSION: Compared
      to CT and PET, EBUS-TBNA has a high sensitivity as well as specificity for
      mediastinal and hilar lymph node staging in patients with lung cancer. EBUS-TBNA
      should be considered for evaluation of the mediastinum early in the staging
      process of lung cancer.

PMID- 16963668
TI  - Outcome and code status of lung cancer patients admitted to the medical ICU.
AB  - OBJECTIVES: To determine the outcome of lung cancer patients admitted to the
      medical ICU (MICU), to examine their code status at MICU admission and prior to
      death, and to determine which subspecialty physician was responsible for the
      change in code status. DESIGN: Retrospective chart review study. SETTING: A 19
      bed MICU in a tertiary-care university hospital. PATIENTS: Consecutive patients
      with a diagnosis of lung cancer admitted to the MICU from July 2002 to June 2004.
      MEASUREMENTS AND MAIN RESULTS: Forty-seven patients with a diagnosis of lung
      cancer accounted for 53 MICU admissions. Mean (+/- SD) age at MICU admission was
      65 +/- 10 years. Sixty-six percent were male. Eighty-three percent had non-small
      cell lung cancer (NSCLC); 64% of these were stage IV NSCLC. The most common organ
      system implicated on MICU admission was pulmonary, with 38% of patients
      presenting with pneumonia. Overall MICU mortality was 43%, and in-hospital
      mortality was 60%. Patients who required mechanical ventilation or had more
      advanced lung cancer stage had the worst prognosis, with mortality rates of 74%
      and 68%, respectively. Seventy-four percent of patients were "full code" at MICU
      admission. Subsequently, the code status was changed to "do not resuscitate" in
      49% of these cases. The pulmonary/critical care physician was involved in this
      change 96% of the time and was the sole physician in 65% of cases. CONCLUSIONS:
      This study confirms that patients with lung cancer admitted to the MICU have a
      high mortality. Despite this, the majority of patients are full code on MICU
      admission. Pulmonary/critical care physicians play an important role in the end
      of-life decision making of lung cancer patients admitted to the MICU, perhaps
      because of their availability in the MICU and also because of their sense of
      responsibility in maintaining and withdrawing life support.

PMID- 16963669
TI  - Etiology and outcomes of pulmonary and extrapulmonary acute lung injury/ARDS in a
      respiratory ICU in North India.
AB  - OBJECTIVE: Outcomes in patients with ARDS/acute lung injury (ALI) may be
      dependent on the underlying cause. We describe the case mix, clinical behavior,
      and outcomes of patients with ALI/ARDS resulting from pulmonary causes
      (ALI/ARDSp) and extrapulmonary causes (ALI/ARDSexp). DESIGN: Retrospective study
      conducted between January 2001 and June 2005. SETTING: Respiratory ICU (RICU) of
      a tertiary care hospital in northern India. PATIENTS: All patients fulfilling the
      criteria for ALI/ARDS and requiring mechanical ventilation for > 24 h.
      MEASUREMENTS AND RESULTS: Of the 180 patients (ARDS, 140 patients; ALI, 40
      patients), 123 patients had ALI/ARDSp, whereas 57 patients had ALI/ARDSexp. The
      most common cause of ALI/ARDSp was infective pneumonia, whereas the most common
      cause of ALI/ARDSexp was sepsis. At ICU admission, although patients with
      ALI/ARDSexp were sicker than those with ALI/ARDSp, there was no difference
      between the two groups of patients in the development of new organ
      dysfunction/failure (Delta sequential organ failure assessment [SOFA] scores) or
      the time to develop the first organ dysfunction/failure (assessed by SOFA
      scores). The median length of RICU stay was similar in the two groups (5 days
      [interquartile range (IQR), 6 days] vs 5 days [IQR, 9.5 days], respectively, in
      patients with ALI/ARDSp and ALI/ARDSexp; p = 0.4). The hospital mortality rate
      was 47.8% and was not significantly different between the two groups (ALI/ARDSp
      group, 43.1%; ALI/ARDSexp group, 57.9%; p = 0.06). Multivariate analysis showed
      the following risk factors for death in the ICU: female gender (odds ratio [OR],
      0.49; 95% confidence interval [CI], 0.25 to 0.94); SOFA scores (OR, 1.18; 95% CI,
      1.07 to 1.3); and DeltaSOFA scores (OR, 1.24; 95% CI, 1.09 to 1.41). There was no
      significant effect of the category of ARDS on outcome (OR, 1.6; 95% CI, 0.8 to
      3.2). CONCLUSIONS: Although patients with ALI/ARDSexp are sicker on ICU
      admission, the underlying cause of ARDS does not affect the length of ICU stay or
      hospital survival time.

PMID- 16963670
TI  - Noninvasive positive-pressure ventilation: An experimental model to assess air
      and particle dispersion.
AB  - BACKGROUND: Health-care workers are concerned about the risk of acquiring
      contagious diseases such as severe acute respiratory syndrome and avian influenza
      after recent outbreaks. We studied exhaled air and particle dispersion through an
      oronasal mask attached to a human-patient simulator (HPS) during noninvasive
      positive-pressure ventilation (NPPV). METHODS: Airflow was marked with
      intrapulmonary smoke for visualization. Therapy with inspiratory positive airway
      pressure (IPAP) was started at 10 cm H2O and gradually increased to 18 cm H2O,
      whereas expiratory positive airway pressure was maintained at 4 cm H2O. A leakage
      jet plume was revealed by a laser light sheet and images captured by video. Smoke
      concentration in the plume was estimated from the light scattered by smoke
      particles. FINDINGS: A jet plume of air leaked through the mask exhaust holes to
      a radial distance of 0.25 m from the mask during the application of IPAP at 10 cm
      H2O with some leakage from the nasal bridge. The leakage plume exposure
      probability was highest about 60 to 80 mm lateral to the median sagittal plane of
      the HPS. Without nasal bridge leakage, the jet plume from the exhaust holes
      increased to a 0.40-m radius from the mask, whereas exposure probability was
      highest about 0.28 m above the patient. When IPAP was increased to 18 cm H2O, the
      vertical plume extended to 0.45 m above the patient with some horizontal
      spreading along the ward ceiling. CONCLUSION: Substantial exposure to exhaled air
      occurs within a 0.5-m radius of patients receiving NPPV. Medical wards should be
      designed with an architectural aerodynamics approach and knowledge of
      air/particle dispersion from common mechanical ventilatory techniques.

PMID- 16963671
TI  - Montelukast treatment attenuates the increase in myofibroblasts following low
      dose allergen challenge.
AB  - RATIONALE: Airway remodeling is believed to be important in the pathophysiology
      of asthma, and myofibroblasts are increased in the airways of asthmatic
      individuals 24 h after allergen challenge. Leukotriene receptor antagonists exert
      antiinflammatory activity in asthma, but it is unknown whether they influence
      indices of airway remodeling. In the present study, we evaluated the effect of
      montelukast on airway myofibroblasts following low-dose allergen challenge
      (LDAC). METHODS: Stable subjects with mild asthma were included in a two-center,
      randomized, parallel-group study. A 2-week run-in period was followed by LDAC and
      endobronchial biopsy. Subjects were then randomized to receive either
      montelukast, 10 mg/d, or placebo (n = 10 in each group) for 8 weeks in a double
      blind manner; at the end of the treatment period, subjects underwent a second
      LDAC and endobronchial biopsy. The effect of treatment on myofibroblasts,
      fibroblasts, and inflammatory cells was examined using electron microscopy
      techniques. RESULTS: Treatment with montelukast showed no significant difference
      by comparison with placebo but did show a significant within-group treatment
      related decrease in airway wall myofibroblasts not seen in the placebo group. In
      addition, the montelukast-treated group also showed a significant within-group
      reduction in lymphomononuclear cells and increased neutrophils. CONCLUSIONS: The
      results suggest that montelukast has an inhibitory effect on airway structural
      cells that play a key role in airway remodeling in allergic airway inflammation,
      and that montelukast may be a useful therapy to attenuate airway remodeling in
      asthma.

PMID- 16963672
TI  - Continuous noninvasive measurement of pulsus paradoxus complements medical
      decision making in assessment of acute asthma severity.
AB  - BACKGROUND: Pulsus paradoxus (PP) is a pathophysiologic parameter that is
      indicative of asthma severity. The ability of PP to categorize acutely asthmatic
      patients in accordance with the earlier National Asthma Education and Prevention
      Program (NAEPP) expert panel report 1 guidelines was determined. METHODS: An
      arterial tonometric BP monitor, which was interfaced to an analog-digital
      converter, executed a periodic amplitude analysis algorithm, which computed PP in
      real time. The PP measurement was compared to the criterion standard of emergency
      physicians in determining the hospital admission vs hospital discharge
      disposition following the NAEPP standardized treatment. Receiver operating
      characteristics (ROCs) were calculated, and the PP threshold, which maximized
      sensitivity and specificity, was identified. In a separate laboratory
      investigation, PP was induced in a healthy volunteer by inspiration through a
      fixed resistance. Plethysmographic waveform changes, induced by PP, were measured
      by a second analog-to-digital converter that was connected to a pulse oximeter.
      RESULTS: A total of 79 patients were enrolled in the study, of whom 63 met a
      priori inclusion criteria and had uninterrupted data acquisition. The mean PP for
      patients who were appropriately discharged from the hospital was 9.1 mm Hg (95%
      confidence interval [CI], 7.3 to 10.9 mm Hg) and differed from the PP of 17.6 mm
      Hg (95% CI, 13.5 to 21.8; p < 0.001) for patients admitted to the
      hospital/relapsed. The sensitivity and specificity for physician disposition were
      0.83 and 0.89, respectively, and for PP values were 0.78 and 0.78, respectively.
      The Wilcoxon area under the ROC curve was 0.82 (95% CI, 0.64 to 0.99) following
      treatment. The risk ratio was 5.32 for hospital admission among patients with a
      PP of > 11.3 mm Hg. Changes in the photoplethysmography peak height were
      correlated to PP from the BP monitor by a regression line with a slope of 0.01
      V/mm Hg. CONCLUSIONS: Continuous PP can aid in determining disposition among
      emergency department (ED) patients with acute asthma. ED physicians equipped with
      a PP monitor would be able to objectify the work of breathing and would more
      closely adhere to NAEPP guidelines. The possibility that a PP detection algorithm
      could reside in a pulse oximeter warrants further investigation.

PMID- 16963673
TI  - Low socioeconomic status is a risk factor for cardiovascular disease among adult
      obstructive sleep apnea syndrome patients requiring treatment.
AB  - STUDY OBJECTIVE: To evaluate the possible role of low socioeconomic status (SES)
      as a risk factor for cardiovascular disease (CVD) among obstructive sleep apnea
      syndrome (OSAS) patients requiring treatment. DESIGN: Polysomnographic and
      demographic characteristics and associated morbidity were measured in 686
      prospectively recruited adult OSAS patients from two regions in Israel. SETTING:
      Two university-affiliated sleep laboratories. MEASUREMENTS AND RESULTS: The
      multiple logistic regression (after adjusting for gender, body mass index [BMI],
      and smoking) revealed that the following are independent determinants for CVD in
      OSAS patients requiring treatment: each decrease in income level category (odds
      ratio [OR], 1.4; 95% confidence interval [CI], 1.1 to 1.7), age > or = 1 year
      (OR, 1.07; 95% CI, 1.04 to 1.1), hypertension (OR, 2.0; 95% CI, 1.3 to 3.1), and
      hyperlipidemia (OR, 3.7; 95% CI, 2.4 to 5.8); area under the receiver operating
      characteristic (ROC) = 81.9%. The multivariate determinants describing the low
      SES OSAS patients included: minorities and immigrants combined (OR, 6.0; 95% CI,
      2.9 to 12), female gender (OR, 2.4; 95% CI, 1.6 to 3.9), increased BMI (OR, 1.9;
      95% CI, 1.3 to 2.9), unmarried status (OR, 1.9; 95% CI, 1.2 to 3.1), and years of
      education (> or = 1 year) [OR, 0.8; 95% CI, 0.7 to 0.8]; area under the ROC =
      78.1%. CONCLUSION: In addition to the already known traditional risk factors, low
      SES was found to be a novel independent risk factor for CVD among adult OSAS
      patients requiring treatment.

PMID- 16963674
TI  - Effect of treatment with nasal continuous positive airway pressure on ventilatory
      response to hypoxia and hypercapnia in patients with sleep apnea syndrome.
AB  - BACKGROUND: The increase in peripheral chemoreflex sensitivity in patients with
      obstructive sleep apnea (OSA) is associated with activation of autonomic nervous
      system and hemodynamic responses. Nasal CPAP (nCPAP) is an effective treatment
      for OSA, but little is known on its effect on chemoreflex sensitivity.
      OBJECTIVES: To assess the effect of nCPAP treatment or placebo (sham nCPAP) on
      ventilatory control in patients with OSA. SETTING: Sleep laboratory of Azienda
      Ospedaliera Garibaldi. PATIENTS: Twenty-five patients with moderate-to-severe
      OSA. DESIGN AND MEASUREMENTS: Patients were randomly assigned to either
      therapeutic nCPAP (use of optimal pressure, n = 15) or sham nCPAP (suboptimal
      pressure of 1 to 2 cm H2O, n = 10) in a double-blind fashion and treated for 1
      month. A rebreathing test to assess ventilatory response to normocapnic hypoxia
      and normoxic hypercapnia was performed at basal condition and after 1 month of
      treatment. RESULTS: The use of therapeutic nCPAP or sham nCPAP did not affect
      daytime percentage of arterial oxygen saturation (SaO2%) or end-tidal P(CO2). The
      normocapnic hypoxic ventilatory response was reduced after 1 month of treatment
      with nCPAP (the slope was 1.08 +/- 0.02 L/min/SaO2% at basal condition and 0.53
      +/- 0.07 L/min/SaO2% after 1 month of treatment, p = 0.008) [mean +/- SD], but
      not in patients treated with sham nCPAP (slope, 0.83 +/- 0.09 L/min/SaO2% and
      0.85 +/- 0.19 L/min/SaO2% at basal condition and after 1 month, respectively).
      The normoxic hypercapnic ventilatory response remained unchanged after 1 month in
      both groups. No changes in ventilatory response to either hypoxia or hypercapnia
      were observed after a single night of nCPAP treatment. CONCLUSION: The
      ventilatory response to hypoxia is reduced during regular treatment, but not
      after short-term treatment, with nCPAP. Readjusted peripheral oxygen
      chemosensitivity during nCPAP treatment may be a side effect of both reduced
      sympathetic activity and increased baroreflex activity, or a possible continuous
      positive airway pressure-related mechanism leading to a reduced activation of
      autonomic nervous system per se.

PMID- 16963675
TI  - Prevalence of symptoms and risk of sleep apnea in the US population: Results from
      the national sleep foundation sleep in America 2005 poll.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a common medical condition with
      significant adverse consequences, but OSA remains undiagnosed in many
      individuals. The Berlin questionnaire is a validated instrument that is used to
      identify individuals who are at risk for OSA. DESIGN: We conducted an analysis of
      data from the Sleep in America 2005 Poll of The National Sleep Foundation (NSF).
      The NSF poll is an annual telephone interview of a representative sample of US
      adults. PARTICIPANTS: The 2005 NSF poll included 1,506 adults. The mean age of
      participants was 49 years (775 were women). MEASUREMENTS: The Berlin
      questionnaire was embedded in the NSF poll. This instrument includes questions
      about snoring, witnessed apneas, self-reported hypertension, and daytime
      sleepiness. Height and weight were included for the calculation of body mass
      index (BMI). The NSF poll included detailed demographic information and extensive
      questions related to all aspects of sleep. RESULTS: Of the 1,506 respondents, 26%
      (31% of men and 21% of women) met the Berlin questionnaire criteria indicating a
      high risk of OSA. The risk of OSA increased up to age 65 years. A significant
      number of obese individuals (57%) were at high risk for OSA. Those whose Berlin
      questionnaire scores indicated a high risk for OSA were more likely to report
      subjective sleep problems, a negative impact of sleep on quality of life, and a
      chronic medical condition than those who were at lower risk. CONCLUSIONS: As many
      as one in four American adults could benefit from evaluation for OSA. Considering
      the serious adverse health and quality-of-life consequences of OSA, efforts to
      expedite diagnosis and treatment are indicated.

PMID- 16963676
TI  - Using local microbiologic data to develop institution-specific guidelines for the
      treatment of hospital-acquired pneumonia.
AB  - BACKGROUND: While current guidelines recommend consideration of local
      microbiologic data when selecting empiric treatment for hospital-acquired
      pneumonia (HAP), few specifics of how to do this have been offered. METHODS: We
      conducted a retrospective analysis of HAP pathogens in 111 consecutive patients
      who acquired HAP during July to December 2004 and had a corresponding positive
      culture finding for a bacterial pathogen. These data were used to develop
      institution-specific guidelines. RESULTS: The most common bacteria identified
      were Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa,
      which were associated with 38%, 25%, and 19% of pneumonias, respectively.
      Susceptibility of Gram-negative bacteria to piperacillin-tazobactam and cefepime
      was 80% and 81%, respectively. The isolation of organisms resistant to
      piperacillin-tazobactam or cefepime was significantly more frequent in patients
      who had been hospitalized > or = 10 days. Of Gram-negative isolates resistant to
      piperacillin-tazobactam or cefepime, ciprofloxacin was active against < 10%,
      while amikacin was active against > 80%. New treatment guidelines were developed
      that divided the American Thoracic Society/Infectious Diseases Society of America
      "late onset/risk of multidrug-resistant pathogens" group of patients into two
      subcategories: "early-late" pneumonias (< 10 days of hospitalization) and "late
      late" pneumonias (> or = 10 days of hospitalization). Guideline-directed
      treatment regimens would be predicted to provide adequate initial therapy for >
      90% of late-onset pneumonias at our institution. CONCLUSIONS: Current guidelines
      suggest adding either an aminoglycoside or a fluoroquinolone to beta-lactam
      therapy for empiric Gram-negative coverage. However, in our institution, adding
      ciprofloxacin would not appreciably enhance the likelihood of providing initial
      appropriate antibiotic coverage. This underscores the importance of employing a
      systematic analysis of local data when developing treatment guidelines.

PMID- 16963677
TI  - Improved clinical outcomes with utilization of a community-acquired pneumonia
      guideline.
AB  - BACKGROUND: We previously reported decreased mortality following implementation
      of a community-acquired pneumonia guideline derived from specialty society
      recommendations. However, patients with respiratory failure and sepsis from
      pneumonia were not included, adjustment for comorbidities was limited, and no
      guideline compliance data were available. We also questioned whether decreased
      mortality continued after 1997. METHODS: We utilized Utah data from the Centers
      for Medicare and Medicaid from 1993 to 2003 to determine if pneumonia guideline
      implementation was associated with 30-day all-cause mortality, length of hospital
      stay, and readmission rate. We adjusted outcomes by age, gender, Deyo comorbidity
      score, prior hospitalizations, and race. Guideline compliance was measured by
      initial default guideline antibiotic administration. We included patients > or =
      66 years old with primary International Classification of Diseases, Ninth
      Revision, Clinical Modification codes 480.0-483.9, 485.0-486.9, 487.0, 507.0 or
      518.81, and 038.x with secondary code pneumonia. We excluded patients with prior
      hospitalization within 10 days, patients with HIV infection or transplant
      recipients, and patients not treated by physicians closely affiliated with study
      hospitals. RESULTS: Mean (+/- SD) age of 17,728 pneumonia patients admitted to
      the hospital was 72.3 +/- 12.0 years, 55.2% were female, and 96.0% were white.
      Within Intermountain Healthcare hospitals, a 1-SD increase (10%) in guideline
      compliance (range, 61 to 100%) was associated with mortality odds ratio (OR) of
      0.92 (95% confidence interval[CI], 0.87 to 0.98; p = 0.007). Mortality OR at 16
      Intermountain Healthcare hospitals was 0.89 (95% CI, 0.82 to 0.97; p = 0.007)
      compared with 19 other Utah hospitals. This mortality difference corresponds to
      approximately 20 lives saved yearly. The readmission rate was also lower.
      CONCLUSION: Improved clinical outcomes were associated with pneumonia guideline
      utilization.

PMID- 16963678
TI  - Hospitalized community-acquired pneumonia due to Streptococcus pneumoniae: Has
      resistance to antibiotics decreased?
AB  - STUDY OBJECTIVES: To determine the incidence and trends of pneumococcal community
      acquired pneumonia (CAP) resistant to antibiotics, to describe clinical and
      microbiological features of pneumococcal CAP, and to ascertain prognostic risk
      factors in a third-level hospital. DESIGN AND SETTING: We performed a prospective
      study of all well-defined pneumococcal CAP hospitalizations in the Hospital
      Clinic de Barcelona (Spain) over 2 years of follow-up, and results were compared
      with a previous study. MEASUREMENTS AND RESULTS: One hundred twenty-five patients
      were included (mean age, 59.6 years; 71.2% male and 28.8% female). Mortality was
      7% (n = 9). Twenty-four percent were HIV-1 seropositive (n = 30), and 53% had at
      least one comorbidity (n = 65). Nonsusceptibility to penicillin, ceftriaxone, and
      erythromycin accounted for 34%, 9%, and 33%, respectively. A decrease in
      penicillin (p = 0.01) and cephalosporin (p < 0.001) resistance was observed on
      comparison with a previous study, while macrolide resistance remained unchanged.
      Serotype 1 infection was overrepresented (8%, n = 10). A bad outcome was related
      to female gender (relative risk [RR], 9.1; confidence interval [CI], 1.3 to
      61.3), pleural effusion (RR, 13.35; CI, 1.9 to 93.1), and prior oral corticoid
      intake (RR, 10.59; CI, 1.2 to 91.2), whereas drug-resistant strains were not.
      CONCLUSIONS: We found a decrease in drug resistance compared with a previous
      report and a relatively high incidence of serotype 1 pneumococcal CAP. We also
      observed a high prevalence of HIV-1 infection among individuals with pneumococcal
      pneumonia. We confirm the lack of association of drug resistance with mortality
      and length of hospitalization. Mortality was associated with female gender,
      pleural effusion, and previous oral corticoid treatment. These results should be
      better ascertained in further studies.

PMID- 16963679
TI  - Resource utilization of adults admitted to a large urban hospital with community
      acquired pneumonia caused by Streptococcus pneumoniae.
AB  - OBJECTIVE: To determine if penicillin-nonsusceptible Streptococcus pneumoniae,
      among other variables, was significantly associated with greater hospital costs
      among patients with community-acquired pneumonia (CAP). DESIGN: Retrospective,
      cohort study. SETTING: Eight hundred ten-bed, urban, private, teaching hospital.
      PATIENTS: Adult patients admitted between 1999 and 2003 with CAP caused by S
      pneumoniae. INTERVENTION: Clinical criteria and costs (inflated to 2004 dollars)
      were collected from the medical charts and detailed hospital bills for each
      individual patient. Costs were compared according to classification by penicillin
      susceptibility. Multivariate linear regression was utilized to determine
      variables independently associated with increased hospital costs and length of
      stay. RESULTS: Of 168 patients included, 44 patients (26%) had CAP caused by
      penicillin-nonsusceptible S pneumoniae. Median total hospital costs were 8,654
      dollars (25th to 75th percentile, 5,457 dollars to 16,027 dollars), with no
      difference between susceptible and nonsusceptible groups. Bed costs accounted for
      55.6% of total costs, followed by laboratory (9.9%) and pharmacy (9.8%) costs.
      Regression analyses determined that ICU admission (p < 0.001), unexplained delays
      in discharge (p = 0.001), and neoplasm (p < 0.04) were independently predictive
      of both total hospital costs (adjusted r2 = 0.46) and increasing length of stay
      (adjusted r2 = 0.30). Hospital mortality, bacteremia, and congestive heart
      failure were also associated with at least one of the dependent variables.
      CONCLUSION: In the current era in which more potent antibiotics are empirically
      utilized to treat CAP, it does not appear that a simple classification of
      penicillin nonsusceptibility complicates the economic impact of S pneumoniae
      infection. Focused efforts to reduce length of stay, including minimizing
      prolonged and unnecessary observation of patients, should have the most profound
      effect on reducing total costs.

PMID- 16963680
TI  - Average volume-assured pressure support in obesity hypoventilation: A randomized
      crossover trial.
AB  - BACKGROUND: Average volume-assured pressure support (AVAPS) has been introduced
      as a new additional mode for a bilevel pressure ventilation (BPV) device (BiPAP;
      Respironics; Murrysville, PA), but studies on the physiologic and clinical
      effects have not yet been performed. There is a particular need to better define
      the most efficient ventilatory treatment modality for patients with obesity
      hypoventilation syndrome (OHS). METHODS: In OHS patients who did not respond to
      therapy with continuous positive airway pressure, the effects of BPV with the
      spontaneous/timed (S/T) ventilation mode with and without AVAPS over 6 weeks on
      ventilation pattern, gas exchange, sleep quality, and health-related quality of
      life (HRQL) assessed by the severe respiratory insufficiency questionnaire (SRI)
      were prospectively investigated in a randomized crossover trial. RESULTS: Ten
      patients (mean [+/- SD] age, 53.5 +/- 11.7 years; mean body mass index, 41.6 +/-
      12.1 kg/m2; mean FEV1/FVC ratio, 79.4 +/- 6.5%; mean transcutaneous P(CO2)
      [PtcCO2], 58 +/- 12 mm Hg) were studied. PtcCO2 nonsignificantly decreased during
      nocturnal BPV-S/T by -5.6 +/- 11.8 mm Hg (95% confidence interval [CI], -14.7 to
      3.4 mm Hg; p = 0.188), but significantly decreased during BPV-S/T-AVAPS by -12.6
      +/- 12.2 mm Hg (95% CI, -22.0 to -3.2 mm Hg; p = 0.015). Pneumotachographic
      measurements revealed a higher individual variance of peak inspiratory pressure
      (p < 0.001) and a trend for lower leak volumes but also for higher tidal volumes
      during BPV-S/T-AVAPS. The SRI summary scale score improved from 63 +/- 15 to 78
      +/- 14 during BPV-S/T (p = 0.004) and to 76 +/- 16 during BPV-S/T-AVAPS (p =
      0.014). Sleep quality and oxygen saturation also comparably improved following
      BPV-S/T and BPV-S/T-AVAPS. CONCLUSION: BPV-S/T substantially improved
      oxygenation, sleep quality, and HRQL in patients with OHS. AVAPS provided
      additional benefits on ventilation quality, thus resulting in a more efficient
      decrease of PtcCO2. However, this did not provide further clinical benefits
      regarding sleep quality and HRQL.

PMID- 16963681
TI  - Airflows around oxygen masks: A potential source of infection?
AB  - Patients with respiratory infections often require the use of supplemental oxygen
      via oxygen masks, which, in the hospital, may become sources of aerosolized
      infectious pathogens. To assess this risk, a human lung model (respiration rate,
      12 breaths/min) was designed to test the potential for a simple oxygen mask at a
      common setting (4 L/min) to disperse potentially infectious exhaled air into the
      surrounding area. A laser sheet was used to illuminate the exhaled air from the
      mask, which contained fine tracer smoke particles. An analysis of captured
      digital images showed that the exhaled air at the peak of simulated exhalation
      reached a distance of approximately 0.40 m.

PMID- 16963682
TI  - The effects of body mass index on lung volumes.
AB  - BACKGROUND: Obesity is a major health issue in North America, and the trend is
      for obesity to be a more important medical issue in the future. Since obesity can
      cause respiratory symptoms, many obese people are referred for pulmonary function
      tests (PFTs). It is well known that obesity causes decreases in lung volumes, but
      there has never been a large study showing the correlation between body mass
      index (BMI) and the various lung volumes. DESIGN: We collected PFT results from
      373 patients sent for lung function testing who had normal values for airway
      function but a wide range of BMIs. SETTING: The PFTs were done in two accredited
      outpatient laboratories. RESULTS: There were significant linear relationships
      between BMI and vital capacity and total lung capacity, but the group mean values
      remained within the normal ranges even for morbidly obese patients. However,
      functional residual capacity (FRC) and expiratory reserve volume (ERV) decreased
      exponentially with increasing BMI, such that morbid obesity resulted in patients
      breathing near their residual volume. An important finding was that the greatest
      rates of change in FRC and ERV occurred in the overweight condition and in mild
      obesity. At a BMI of 30 kg/m2, FRC and ERV were only 75% and 47%, respectively,
      of the values for a lean person with a BMI of 20 kg/m2. CONCLUSIONS: We showed
      that BMI has significant effects on all of the lung volumes, and the greatest
      effects were on FRC and ERV, which occurred at BMI values < 30 kg/m2. Our results
      will assist clinicians when interpreting PFT results in patients with normal
      airway function.

PMID- 16963683
TI  - Simulated obesity-related changes in lung volume increases airway responsiveness
      in lean, nonasthmatic subjects.
AB  - STUDY OBJECTIVE: To determine if obesity-related changes in lung volume might
      contribute to airway reactivity, we investigated the effects of simulated mild
      obesity-related lung volume reductions on airway responsiveness in lean,
      nonasthmatic subjects. PARTICIPANTS AND METHODS: We simulated the lung volume
      reductions of class 1 obesity in eight lean, nonasthmatic subjects by externally
      mass loading the chest wall and abdomen, and shifting blood volume into the lung
      with lower limb compression (LLC). Airway responsiveness was assessed by
      measuring FEV(1) before and after methacholine challenge tests (1, 2.5, 5, 10,
      and 25 mg/mL) with the following: (1) no intervention (control); (2) external
      chest loading (CL); (3) LLC; and (4) CL and LLC (COMB) on separate days. Lung
      function was measured before and after CL, LLC, and COMB were applied. RESULTS:
      The application of CL, LLC, and COMB decreased expiratory reserve volume,
      functional residual capacity, and total lung capacity compared with baseline. FVC
      and FEV(1) decreased significantly with CL and COMB, while FEV(1)/FVC did not
      change compared to baseline. The maximal response to the methacholine challenge
      increased with CL, LLC, and COMB, with a mean maximal fall of FEV(1) of 9%, 11%,
      and 18%, respectively, compared to a 6% fall with control. CONCLUSIONS: We
      conclude that decreases in lung volume increase airway responsiveness and may
      account for the increased propensity for increased airway responsiveness in the
      obese.

PMID- 16963684
TI  - Chronic thromboembolic and pulmonary arterial hypertension share acute
      vasoreactivity properties.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) and chronic thromboembolic
      pulmonary hypertension (CTEPH) are the major classes of pulmonary hypertensive
      disorders according to the World Health Organization; both lead to right heart
      failure and death. A better understanding of disease mechanisms has led to the
      suggestion that the thromboembolic and nonthromboembolic types of pulmonary
      hypertension may share pathophysiologic features. We therefore compared acute
      vasoreactivity and proximal pulmonary artery compliance in patients with PAH and
      CTEPH during the initial diagnostic heart catheterization. METHODS: Right heart
      catheterization using a flow-directed Swan-Ganz catheter was performed in
      patients with CTEPH (n = 22) and PAH (n = 35). Pulmonary hemodynamics were
      assessed at baseline, during the inhalation of 40 ppm of nitric oxide, and 30 min
      after the inhalation of 10 mug of iloprost. To assess the proximal pulmonary
      artery compliance, the pulse pressure (PP) [systolic-diastolic pressure] and the
      fractional PP (PPf) [divided by the mean pressure] were calculated. RESULTS: Both
      vasodilators produced similar hemodynamic improvement, and the difference between
      CTEPH and PAH was not significant. The baseline PP and PPf did not vary between
      the two groups. CONCLUSION: Patients with PAH and CTEPH show similar acute
      vasoreactivity to inhaled nitric oxide and iloprost, and have similar pulmonary
      artery compliance. These findings support the presence of some shared
      pathophysiologic pathways in both disorders and may lead to therapeutic
      implications in patients with inoperable CTEPH.

PMID- 16963685
TI  - Sequential gene expression profiling in lung transplant recipients with chronic
      rejection.
AB  - STUDY OBJECTIVES: Chronic allograft rejection is the leading cause of morbidity
      and mortality for long-term survivors of lung transplantation. Previous studies
      have implicated only isolated genes in the development of chronic rejection and
      have not examined multiple pathways in an individual concurrently. Using
      microarray technology, we identified and compared gene expression profiling in
      lung transplant recipients with and without chronic rejection, and follow
      sequential expression of genes differentially expressed between the two groups.
      DESIGN: Prospective, cohort study. SETTING: Single lung transplant center.
      PATIENTS OR PARTICIPANTS: Eleven transplant recipients with chronic rejection
      were matched with 9 control transplant recipients. INTERVENTIONS: All recipients
      underwent surveillance bronchoscopies at predetermined times to rule out
      infection and/or acute rejection. Gene expression profiling was obtained from
      hybridizing BAL fluid cell RNA to a 96-gene microarray. MEASUREMENTS AND RESULTS:
      Fifteen genes were found to be significantly differentially expressed between the
      two patient groups, and they are involved in inflammatory, fibrotic, and
      apoptotic pathways. Temporal expression of the significant genes demonstrated a
      change in their levels at the onset of chronic rejection, with normalization to
      prerejection levels as rejection continued. CONCLUSIONS: We conclude that
      microarray technology is valuable in studying the mechanism of chronic lung
      rejection, and the expression of genes in multiple pathways is elevated in
      patients with chronic lung rejection.

PMID- 16963686
TI  - Comparison of sarcoidosis phenotypes among affected African-American siblings.
AB  - STUDY OBJECTIVE: To test the hypothesis that sibling pairs, who share genes and
      environmental exposures, might have similar phenotypic expressions of sarcoidosis
      beyond what would be expected by chance alone. DESIGN: Multicenter family study
      with study subjects recruited from 11 clinical centers. SUBJECTS: Subjects were
      African-American sibling pairs with sarcoidosis. Sarcoidosis and organ pattern
      involvement were defined according to specific criteria. Fifteen different organ
      systems were evaluated. RESULTS: For full-sibling pairs, ocular involvement was
      found in both siblings more often than expected by chance alone (p < 0.05), but
      the concordance was weak (kappa = 0.18). When analyzing full-sibling and half
      sibling pairs, ocular and liver involvement showed a significant concordance
      between sibling pairs (p < 0.05), but again the agreement was poor (kappa = 0.16
      for both). Concordance in pulmonary function change over time was also weak.
      Clinical outcomes of sibling pairs were not significantly correlated except for
      whether treatment was prescribed, and this level of agreement was poor (kappa =
      0.14 for full-sibling and half-sibling pairs; kappa = 0.15 for full-sibling pairs
      only). Modeling phenotypic expression in sibling pairs using logistic regression
      did show that the presence of ocular and liver sarcoidosis in the first affected
      sibling conferred a statistically significant increased risk to the second
      affected sibling for having those organs involved (odds ratio [OR], 3; 95%
      confidence interval [CI], 1.7 to 5.4 for ocular; OR, 3.3; 95% CI, 1.5 to 7.4 for
      liver). CONCLUSIONS: The phenotypic features and clinical outcomes of sarcoidosis
      in sibling pairs show minimal concordance, with the possible exception that the
      presence of ocular or liver involvement in the first sibling with a diagnosis of
      sarcoidosis makes involvement of these organs more likely in other affected
      siblings.

PMID- 16963687
TI  - Evaluation of rabbit tracheal inflammation using optical coherence tomography.
AB  - BACKGROUND: Optical coherence tomography (OCT) is an evolving technology that is
      capable of delivering real-time, high-resolution images of tissues. The purpose
      of this study was to evaluate the feasibility of using OCT for detecting airway
      pathology in a septic animal model. METHODS: The tracheas of New Zealand white
      rabbits were inoculated endobronchially with various concentrations of live
      Streptococcus pneumoniae bacteria. After the development of pneumonia/sepsis, the
      animals were killed. OCT tracheal images and corresponding histologic specimens
      from these experimental animals were compared to control rabbit tracheas for
      morphologic features and quantitative tracheal mucosal thickness measurements.
      RESULTS: The results revealed significant airway mucosal thickening in the
      experimental group that was consistent with tracheal edema. Morphologic changes,
      including epithelial denuding and mucosal sloughing, were evident in regions of
      the experimental tracheas. CONCLUSION: This study suggests that OCT is a
      potentially valuable imaging modality that is capable of evaluating superficial
      airway pathology with high-resolution in vivo images. Numerous applications of
      OCT can be envisioned in the realm of pulmonary medicine and thoracic surgery
      that may substantially increase the precision and accuracy of current
      bronchoscopic diagnostic and surgical techniques.

PMID- 16963688
TI  - Long-term neurocognitive function after critical illness.
AB  - BACKGROUND: Until relatively recently, critical care practitioners have focused
      on the survival of their patients and not on long-term outcomes. The incidence of
      chronic neurocognitive dysfunction has been underestimated and underreported, and
      only recently has it been studied in critically ill patients. However,
      neurocognitive outcomes have been the subject of extensive investigation in other
      medical populations for many years. METHODS: Review of the current literature
      regarding long-term neurocognitive outcomes following critical illness. RESULTS:
      Data from studies to date indicate that critical illness can lead to significant
      neurocognitive impairments. The neurocognitive impairments persist for months and
      years, and may have important consequences for quality of life, the ability to
      return to work, overall functional ability, and substantial economic costs. The
      mechanisms of the neurocognitive impairments are not fully understood but likely
      include delirium, hypoxia, glucose dysregulation, metabolic derangements,
      inflammation, and the effects of sedatives and narcotics among other factors. The
      contributions of these factors may be particularly significant in patients with
      preexisting vulnerabilities for the development of cognitive impairments such as
      mild cognitive impairment, dementia, prior traumatic brain injury, or other
      comorbid disorders associated with neurocognitive impairments. CONCLUSIONS:
      Current research indicates that neurocognitive sequelae following critical
      illness are common, may be permanent, and are associated with impairments in
      daily function, decreased quality of life, and an inability to return to work.
      Research needs to be done to better understand the prevalence, nature, risk
      factors, and nuances of the neurocognitive impairments observed in ICU survivors.

PMID- 16963689
TI  - Gene therapy for pulmonary diseases.
AB  - Gene therapy has not yet met the high expectations of "the early days." However,
      it is a promising new treatment for lung diseases. Not only single gene disorders
      such as CF are potential candidates for gene therapy, but also cancer and chronic
      lung diseases characterized by an imbalance of damaging and protective
      mechanisms. This review summarizes the recent advances in the development of more
      efficient gene transfer systems and highlights areas of clinical application of
      gene therapy.

PMID- 16963690
TI  - Pulmonary practice profiles: Results of a practice performance survey.
AB  - OBJECTIVES: Physician productivity, practice expense, resource allocation,
      facilities, staff, and malpractice are variables in medical practice
      profitability. The ongoing challenge of collecting reliable and consistent data
      created an opportunity in 2001 for the American College of Chest Physicians
      (ACCP) Practice Administration Network (PAN) to develop a practice-based survey
      that measured the variables most related to the bottom line. METHODS: The PAN
      designed a comprehensive practice survey in 2001 that has been distributed to >
      2,000 ACCP members each year. The specialty-specific survey differed from those
      offered in the market, as its aim was to capture information about pulmonary,
      critical care, and sleep practices. The single-answer survey included practice
      expense categories and those related to accounts receivable management. An on
      line survey vendor (www.surveymonkey.com) was selected as the platform based on
      broad functionality and a flexible architecture. RESULTS: The survey was
      conducted each June for 5 consecutive years. In 2001, survey respondents
      represented 68 pulmonary physicians. By 2005, 229 practices responded
      representing 774 individual physicians. Participants included members of ACCP
      Leadership, ACCP Committees, and related networks, and past survey participants.
      The data are presented in graphic format as a percentage of total respondents.
      CONCLUSION: The survey offered participants a mechanism to contrast and compare
      specialty-based trends in practice expense, staffing levels, clinical services,
      malpractice cost, facilities utilization, and financial management strategies of
      "better performing" practices. It has served as the groundwork for related
      Practice Management Committee and Practice Management Department initiatives. The
      ACCP anticipates future survey collaboration with the Medical Group Management
      Association.

PMID- 16963691
TI  - The association between obesity and asthma is stronger in nonallergic than
      allergic adults.
AB  - STUDY OBJECTIVE: To determine the modifying effects of sex and allergy history on
      the association between body mass index (BMI) and asthma prevalence. DESIGN:
      Cross-sectional study of 86,144 Canadians who were 20 to 64 years of age in 2000
      2001. SETTING: A national survey. MEASUREMENTS AND ANALYSIS: Self-reported
      asthma, allergy history, height, and weight. Logistic regression analysis was
      used to detect effect modification and to adjust for covariates. Population
      weight and design effects associated with complex survey design were taken into
      consideration. RESULTS: The adjusted odds ratios (ORs) for obesity associated
      with asthma was 1.85 (95% confidence interval [CI], 1.65 to 2.07) for women and
      1.21 (95% CI, 1.05 to 1.40) for men. One unit of increased BMI was associated
      with an approximate 6% increase in asthma risk in women, and 3% in men. A
      stronger association between obesity and asthma was observed in nonallergic women
      than in allergic women, with the adjusted ORs being 2.53 (95% CI, 2.11 to 3.04)
      and 1.57 (95% CI, 1.36 to 1.82), respectively. For men, the corresponding ORs
      were 1.30 (95% CI, 1.05 to 1.62) and 1.18 (95% CI, 0.98 to 1.53), respectively.
      CONCLUSIONS: Obesity is likely to have a larger effect on nonallergic asthma. The
      greater prevalence of nonallergic asthma in women may explain the stronger
      obesity-asthma association seen in women compared with men and children who have
      a greater prevalence of allergic asthma.

PMID- 16963692
TI  - The relationship between migraine and right-to-left shunt: Fact or fiction?
AB  - The prevalence of a right-to-left shunt, both cardiac and pulmonary, is high in
      patients with migraines, especially migraine with aura. Percutaneous closure of a
      right-to-left shunt seems to be associated with a pronounced decrease in the
      number of migraine attacks or its prevalence. In this review, the relationship
      between migraine and right-to-left shunting is described by highlighting the
      different pathophysiologic hypotheses.

PMID- 16963694
TI  - First use of ventricular septal defect occlusion device for endoscopic closure of
      an esophagorespiratory fistula using bronchoscopy and esophagoscopy.
AB  - A 70-year-old woman presented with a persistent, nonmalignant esophagorespiratory
      fistula. Since other treatment options failed or were denied, an experimental
      nonsurgical therapy was performed. A self-expanding ventricular septal defect
      (VSD) occlusion device (Amplatzer; AGA Medical Corporation; Golden Valley, MN)
      was bronchoscopically introduced to close the fistula. The double umbrella-like
      occlusion device is made from nitinol mesh and closes luminal contact between the
      esophageal and bronchial walls, with its waist filling out the fistula itself.
      The geometry of the occluder system can in theory be designed according to
      individual purposes and needs. The performed treatment was safe and successful,
      and the patient remained asymptomatic for 1 year after the first presentation.
      The treatment of chronic nonmalignant esophagorespiratory fistulas can be
      difficult. The self-expanding VSD occluder system described in this case might be
      useful in patients who are not surgical candidates.

PMID- 16963693
TI  - Sleep apnea and commercial motor vehicle operators: Statement from the joint task
      force of the American College of Chest Physicians, the American College of
      Occupational and Environmental Medicine, and the National Sleep Foundation.

PMID- 16963695
TI  - Management of obstructing pulmonary broncholithiasis with three-dimensional
      imaging and holmium laser lithotripsy.
AB  - Major airway obstruction due to broncholithiasis produces significant morbidity,
      and management is difficult. Many of the patients are elderly and are not good
      candidates for surgical removal. Bronchoscopic removal may be limited due to
      anatomic considerations, skill of the bronchoscopist, and exposure of the patient
      to additional procedural risks. Preprocedural planning with three-dimensional
      (3D) multidetector CT (MDCT) imaging enhances the bronchoscopist's knowledge of
      the relationships of the target lesions with critical structures, and improves
      the efficiency of the application of specific endobronchial therapies. Here we
      report our experience treating obstructing broncholithiasis in two patients
      utilizing pretreatment planning with 3D MDCT imaging, followed by
      bronchoscopically delivered holmium laser fragmentation of the stones.

PMID- 16963696
TI  - Hypersomnias of central origin.
AB  - Hypersomnia related to CNS disorders can be due to a variety of conditions. In
      this review, we discuss the diagnosis and treatment of narcolepsy with and
      without cataplexy, idiopathic hypersomnia, recurrent hypersomnia, and related
      illnesses. Research has provided insight into the underlying etiologies of these
      disorders, such as the genetic influences on disease development and the
      fundamental role of hypocretins in narcolepsy. We define the current utility of
      diagnostic testing, including sleep studies, neuroimaging techniques, and
      laboratory investigations. New treatment options for hypersomnia are discussed.

PMID- 16963697
TI  - Goodbye Ghostwriters!: How to work ethically and efficiently with professional
      medical writers.

PMID- 16963698
TI  - A 57-year-old woman with fever and abnormal chest CT findings.

PMID- 16963699
TI  - The Salmeterol Multicenter Asthma Research Trial.

PMID- 16963700
TI  - Cause of death in the SMART Trial.

PMID- 16963701
TI  - Why SMART about second-line treatment when first-line treatment is being ignored?

PMID- 16963702
TI  - Comments on the Salmeterol Multicenter Asthma Research Trial.

PMID- 16963703
TI  - Disposable vs reusable bronchoscope valves.

PMID- 16963704
TI  - Comparative genomics modeling of the NRSF/REST repressor network: from single
      conserved sites to genome-wide repertoire.
AB  - We constructed and applied an open source informatic framework called Cistematic
      in an effort to predict the target gene repertoire for transcription factors with
      large binding sites. Cistematic uses two different evolutionary conservation
      filtering algorithms in conjunction with several analysis modules. Beginning with
      a single conserved and biologically tested site for the neuronal repressor
      NRSF/REST, Cistematic generated a refined PSFM (position specific frequency
      matrix) based on conserved site occurrences in mouse, human, and dog genomes.
      Predictions from this model were validated by chromatin immunoprecipitation
      (ChIP) followed by quantitative PCR. The combination of transfection assays and
      ChIP enrichment data provided an objective basis for setting a threshold for
      membership and rank-ordering a final gene cohort model consisting of 842 high
      confidence sites in the human genome associated with 733 genes. Statistically
      significant enrichment of NRSE-associated genes was found for neuron-specific
      Gene Ontology (GO) terms and neuronal mRNA expression profiles. A more extensive
      evolutionary survey showed that NRSE sites matching the PSFM model exist in
      roughly similar numbers in all fully sequenced vertebrate genomes but are notably
      absent from invertebrate and protochordate genomes, as is NRSF itself. Some
      NRSF/REST sites reside in repeats, which suggests a mechanism for both ancient
      and modern dispersal of NRSEs through vertebrate genomes. Multiple predicted
      sites are located near neuronal microRNA and splicing-factor genes, and these
      tested positive for NRSF/REST occupancy in vivo. The resulting network model
      integrates post-transcriptional and translational controllers, including
      candidate feedback loops on NRSF and its corepressor, CoREST.

PMID- 16963705
TI  - Doubling genome size without polyploidization: dynamics of retrotransposition
      driven genomic expansions in Oryza australiensis, a wild relative of rice.
AB  - Retrotransposons are the main components of eukaryotic genomes, representing up
      to 80% of some large plant genomes. These mobile elements transpose via a "copy
      and paste" mechanism, thus increasing their copy number while active. Their
      accumulation is now accepted as the main factor of genome size increase in higher
      eukaryotes, besides polyploidy. However, the dynamics of this process are poorly
      understood. In this study, we show that Oryza australiensis, a wild relative of
      the Asian cultivated rice O. sativa, has undergone recent bursts of three LTR
      retrotransposon families. This genome has accumulated more than 90,000
      retrotransposon copies during the last three million years, leading to a rapid
      twofold increase of its size. In addition, phenetic analyses of these
      retrotransposons clearly confirm that the genomic bursts occurred posterior to
      the radiation of the species. This provides direct evidence of retrotransposon
      mediated variation of genome size within a plant genus.

PMID- 16963706
TI  - Genomic organization of the Drosophila telomere retrotransposable elements.
AB  - The emerging sequence of the heterochromatic portion of the Drosophila
      melanogaster genome, with the most recent update of euchromatic sequence, gives
      the first genome-wide view of the chromosomal distribution of the telomeric
      retrotransposons, HeT-A, TART, and Tahre. As expected, these elements are
      entirely excluded from euchromatin, although sequence fragments of HeT-A and TART
      3 untranslated regions are found in nontelomeric heterochromatin on the Y
      chromosome. The proximal ends of HeT-A/TART arrays appear to be a transition zone
      because only here do other transposable elements mix in the array. The sharp
      distinction between the distribution of telomeric elements and that of other
      transposable elements suggests that chromatin structure is important in telomere
      element localization. Measurements reported here show (1) D. melanogaster
      telomeres are very long, in the size range reported for inbred mouse strains
      (averaging 46 kb per chromosome end in Drosophila stock 2057). As in organisms
      with telomerase, their length varies depending on genotype. There is also slight
      under-replication in polytene nuclei. (2) Surprisingly, the relationship between
      the number of HeT-A and TART elements is not stochastic but is strongly
      correlated across stocks, supporting the idea that the two elements are
      interdependent. Although currently assembled portions of the HeT-A/TART arrays
      are from the most-proximal part of long arrays, approximately 61% of the total
      HeT-A sequence in these regions consists of intact, potentially active elements
      with little evidence of sequence decay, making it likely that the content of the
      telomere arrays turns over more extensively than has been thought.

PMID- 16963708
TI  - Large-scale intron conservation and order-of-magnitude variation in intron
      loss/gain rates in apicomplexan evolution.
AB  - The age of modern introns and the evolutionary forces controlling intron loss and
      gain remain matters of much debate. In the case of the apicomplexan malaria
      parasite Plasmodium falciparum, previous studies have shown that while the
      positions of two thirds of P. falciparum introns are not shared with surveyed non
      apicomplexans (leaving open the possibility that they were relatively recently
      gained), 99.1% are shared with Plasmodium yoelii, which diverged from P.
      falciparum at least 100 Mya. We show here that 60.6% of P. falciparum intron
      positions in conserved regions are shared with the distantly related apicomplexan
      Theileria parva, whereas only 18.2% of introns in the more intron-rich T. parva
      are shared with P. falciparum. Comparison of 3305 pairs of orthologous genes
      between T. parva and Theileria annulata showed that 7089/7111 (99.7%) introns in
      conserved regions are shared between species. These levels of conservation imply
      significant differences in rates of intron loss and gain through apicomplexan
      history. Because transposable elements (TEs) and/or (often TE-encoded) reverse
      transcriptase are implicated in models of intron loss and gain, the observed low
      rates of intron loss and gain in recent Plasmodium and Theileria evolution are
      consistent with the lack of known TE in those groups. We suggest that intron
      loss/gain in some eukaryotic lineages may be concentrated in relatively short
      episodes coincident with occasional TE invasions.

PMID- 16963709
TI  - Mapping of the juxtacentromeric heterochromatin-euchromatin frontier of human
      chromosome 21.
AB  - Euchromatin and heterochromatin are functional compartments of the genome.
      However, little is known about the structure and the precise location of the
      heterochromatin-euchromatin boundaries in higher eukaryotes. Constitutive
      heterochromatin in centromeric regions is associated with (1) specific histone
      methylation patterns, (2) high levels of DNA methylation, (3) low recombination
      frequency, and (4) the repression of transcription. All of this contrasts with
      the permissive structure of euchromatin found along chromosome arms. On the
      sequence level, the transition between these two domains consists most often of
      patchworks of segmental duplications. We present here a comprehensive analysis of
      gene expression, DNA methylation in CpG islands, distribution of histone
      isoforms, and recombination activity for the juxtacentromeric (or
      pericentromeric) region of the long arm of human chromosome 21. We demonstrate
      that most HapMap data are reliable within this region. We show that high linkage
      disequilibrium between pairs of SNPs extends 719-737 kb from the centromeric
      alpha-satellite. In the same region we find a peak of histone isoforms H3K9Me3
      and H3K27Me (715-822 kb distal to the alpha-satellite). In normal somatic cells,
      CpG islands proximal to this peak are highly methylated, whereas distal CpG
      islands are not or very little methylated. This methylation profile undergoes
      dramatic changes in cancer cells and during spermatogenesis. As a consequence,
      transcription from heterochromatic genes is activated in the testis, and aberrant
      gene activation can occur during neoplastic transformation. Our data indicate
      that the frontier between the juxtacentromeric heterochromatic domain and
      euchromatic domain of the long arm of chromosome 21 is marked by a
      heterochromatic peak located approximately 750 kb distal to the alpha-satellite.

PMID- 16963707
TI  - Identifying gene regulatory elements by genomic microarray mapping of DNaseI
      hypersensitive sites.
AB  - The identification of cis-regulatory elements is central to understanding gene
      transcription. Hypersensitivity of cis-regulatory elements to digestion with
      DNaseI remains the gold-standard approach to locating such elements. Traditional
      methods used to identify DNaseI hypersensitive sites are cumbersome and can only
      be applied to short stretches of DNA at defined locations. Here we report the
      development of a novel genomic array-based approach to DNaseI hypersensitive site
      mapping (ADHM) that permits precise, large-scale identification of such sites
      from as few as 5 million cells. Using ADHM we identified all previously
      recognized hematopoietic regulatory elements across 200 kb of the mouse T-cell
      acute lymphocytic leukemia-1 (Tal1) locus, and, in addition, identified two novel
      elements within the locus, which show transcriptional regulatory activity. We
      further validated the ADHM protocol by mapping the DNaseI hypersensitive sites
      across 250 kb of the human TAL1 locus in CD34+ primary stem/progenitor cells and
      K562 cells and by mapping the previously known DNaseI hypersensitive sites across
      240 kb of the human alpha-globin locus in K562 cells. ADHM provides a powerful
      approach to identifying DNaseI hypersensitive sites across large genomic regions.

PMID- 16963710
TI  - Ultrasensitive RNA profiling: counting single molecules on microarrays.

PMID- 16963711
TI  - A systematic, ligation-based approach to study RNA modifications.
AB  - Over 100 different chemical types of modifications have been identified in
      thousands of sites in tRNAs, rRNAs, mRNAs, small nuclear RNAs, and other RNAs.
      Some modifications are highly conserved, while others are more specialized. They
      include methylation of bases and the ribose backbone, rotation, and reduction of
      uridine, base deamination, elaborate addition of ring structures, carbohydrate
      moieties, and more. We have developed a systematic approach to detect and
      quantify the extent of known RNA modifications. The method is based on the
      enzymatic ligation of oligonucleotides using the modified or unmodified RNA as
      the template. The efficiency of ligation is very sensitive to the presence and
      the type of modifications. First, two oligo pairs for each type of modification
      are identified. One pair greatly prefers ligation using the unmodified RNA
      template over the modified RNA template or vice versa. The other pair has equal
      reactivity with unmodified and modified RNA. Second, separate ligations with each
      of the two oligo pairs and the total RNA mixture are performed to detect the
      presence or absence of modifications. Multiple modification sites can be examined
      in the same ligation reaction. The feasibility of this method is demonstrated for
      three 2'O-methyl modification sites in yeast rRNA.

PMID- 16963712
TI  - Treatment of periocular and non-ocular sarcoids in 18 horses by interstitial
      brachytherapy with iridium-192.
AB  - Treatment of the equine sarcoid has posed a significant challenge to clinicians
      for years and many different methods have been tried with varying success,
      including ionising radiation. The aim of this study was to review the efficacy of
      iridium-192 interstitial brachytherapy for the treatment of eight periocular
      sarcoids and 15 non-ocular sarcoids on 18 horses. All the periocular sarcoids and
      13 of the 15 non-ocular sarcoids were treated successfully.

PMID- 16963713
TI  - Cytokine gene signatures in neural tissue of horses with equine protozoal
      myeloencephalitis or equine herpes type 1 myeloencephalopathy.
AB  - This study was designed to determine the relative levels of gene transcription of
      selected pathogens and cytokines in the brain and spinal cord of 12 horses with
      equine protozoal myeloencephalitis (EPM), 11 with equine herpesvirus type 1 (EHV
      1) myeloencephalopathy, and 12 healthy control horses by applying a real time pcr
      to the formalin-fixed and paraffin-embedded tissues. Total rna was extracted from
      each tissue, transcribed to complementary dna (cDNA) and assayed for Sarcocystis
      neurona, Neospora hughesi, EHV-1, equine GAPDH (housekeeping gene), tumour
      necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1beta, IL
      2, IL-4, IL-6, IL-8, IL-10 AND IL-12 p40. S neurona cdna was detected in the
      neural tissue from all 12 horses with EPM, and two of them also had amplifiable
      cDNA of N hughesi. The relative levels of transcription of protozoal cdna ranged
      from 1 to 461 times baseline (mean 123). All the horses with ehv-1
      myeloencephalopathy had positive viral signals by PCR with relative levels of
      transcription ranging from 1 to 1618 times baseline (mean 275). All the control
      horses tested negative for S neurona, N hughesi and EHV-1 cdna. The cytokine
      profiles of each disease indicated a balance between pro- and anti-inflammatory
      markers. In the horses with epm the pro-inflammatory Th1 cytokines (IL-8, TNF
      alpha and IFN-gamma) were commonly expressed but the anti-inflammatory Th2
      cytokines (IL-4, IL-6 AND IL-10) were absent or rare. In the horses with ehv-1
      the proinflammatory cytokine IL-8 was commonly expressed, but IL-10 and IFN-gamma
      were not, and TNF-alpha was rare. Tissue from the control horses expressed only
      the gene GAPDH.

PMID- 16963714
TI  - Evidence of bias affecting the interpretation of the results of local anaesthetic
      nerve blocks when assessing lameness in horses.
AB  - Eighteen observers were influenced to different extents in the grades of lameness
      they allocated to eight horses by whether they knew that a nerve block had been
      administered; on a scale from 0 to 10 the mean difference in grade allocated once
      the observer knew a horse had been nerve-blocked was increased by 0.4. The
      consistency of the assessments made by the individual observers was good, with a
      an average of 0.6 of a grade difference when grading the same horse on two
      occasions. The agreement between the assessments of four orthopaedic experts was
      reasonable (+/-1 grade), but significantly poorer for four non-experts and 10
      final year veterinary students.

PMID- 16963715
TI  - Treatment of Coccidioides immitis pneumonia in two horses with fluconazole.
AB  - Pulmonary coccidioidomycosis in horses can often lead to severe systemic disease
      and its treatment has previously been expensive and has carried a poor prognosis.
      This paper describes the successful treatment of two horses with pulmonary
      coccidioidomycosis with a fluconazole product produced by a compounding pharmacy.

PMID- 16963716
TI  - Septic bicipital bursitis, tendonitis and arthritis of the scapulohumeral joint
      in a mare.

PMID- 16963717
TI  - Standing thoracoscopy in the diagnosis of lymphosarcoma in a horse.

PMID- 16963718
TI  - Tachypnoea and pleural effusion in a mare with metastatic pancreatic
      adenocarcinoma.

PMID- 16963719
TI  - Intraosseous epidermoid cyst of the third phalanx in a thoroughbred gelding.

PMID- 16963720
TI  - Congenital perianal fistula in a thoroughbred colt.

PMID- 16963721
TI  - Retroviraemia and low health status in pigs.

PMID- 16963722
TI  - Epidemic finch mortality.

PMID- 16963723
TI  - Primary epilepsy in the Italian spinone.

PMID- 16963724
TI  - Practitioners' views.

PMID- 16963725
TI  - Substance abuse prevention program content: systematizing the classification of
      what programs target for change.
AB  - We conducted an analysis of programs listed on the National Registry of Effective
      Programs and Practices as of 2003. This analysis focused on programs that
      addressed substance abuse prevention from among those on the effective or model
      program lists and that had manuals. A total of 48 programs met these inclusion
      criteria. We coded program manuals for content that was covered based on how much
      time was devoted to changing targeted mediating variables. The value of this
      approach is that program content can be judged using an impartial standard that
      can be applied to a wide range of intervention approaches. On average, programs
      addressed eight of 23 possible content areas. Our analyses suggested there were
      seven distinguishable approaches that have been used in substance abuse
      prevention programs. These include (i) changing access within the environment,
      (ii) promoting the development of personal and social skills, (iii) promoting
      positive affiliation, (iv) addressing social influences, (v) providing social
      support and helping participants develop goals and alternatives, (vi) developing
      positive schools and (vii) enhancing motivation to avoid substance use. We
      propose that the field use such analyses as the basis of future theory
      development.

PMID- 16963726
TI  - Recruitment and retention of Latinos in a primary care-based physical activity
      and diet trial: The Resources for Health study.
AB  - Mandates to include women and minority populations in research have heightened
      the need to identify successful recruitment strategies. This paper describes the
      recruitment and retention strategies used as part of a randomized controlled
      trial (RCT) of a physical activity and dietary intervention targeting low-income,
      predominantly Latino patients in a primary health care clinic. Data on the
      recruitment and retention rates and the representativeness of participants are
      presented. Strategies included hiring bilingual staff, translating and culturally
      adapting intervention materials and soliciting ongoing consultation from
      patients, clinicians and organizations providing services to the Latino
      community. The primary recruitment procedure involved letters from physicians
      followed by phone calls from project staff to patients identified from electronic
      medical records. Two hundred patients were recruited into the RCT (78% of those
      reached and eligible), with 69 and 81% reached for the 6-week and 6-month follow
      ups, respectively. Women were more likely to both participate and remain in the
      trial, and there was a trend toward greater recruitment and retention of Spanish
      speakers. By engaging the community, clinicians and patients, this study was able
      to successfully recruit and retain a large proportion of this often difficult to
      reach Latino sub-population of patients with multiple chronic conditions.

PMID- 16963727
TI  - Prevention of obesity and eating disorders: a consideration of shared risk
      factors.
AB  - In response to the high prevalence of obesity, eating disorders and disordered
      eating behaviors among youth, researchers in both the obesity and eating
      disorders fields have proposed using an integrated approach to prevention that
      addresses the spectrum of weight-related disorders within interventions. The
      identification of risk factors that are shared between these weight-related
      disorders is an essential step to developing effective prevention interventions.
      This article provides preliminary support for the existence of shared risk
      factors for obesity and eating disorders. Specifically, the authors examined and
      found preliminary evidence that dieting, media use, body image dissatisfaction
      and weight-related teasing may have relevance for the development of the spectrum
      of weight-related disorders. Future etiologic research designed to specifically
      test these and other potentially shared risk factors is needed and would provide
      important insights into the relevant factors to be addressed in interventions
      aimed at preventing a broad spectrum of weight-related disorders.

PMID- 16963728
TI  - Increased expression of urokinase-type plasminogen activator mRNA determines
      adverse prognosis in ErbB2-positive primary breast cancer.
AB  - PURPOSE: To evaluate and validate mRNA expression markers capable of identifying
      patients with ErbB2-positive breast cancer associated with distant metastasis and
      reduced survival. PATIENTS AND METHODS: Expression of 60 genes involved in breast
      cancer biology was assessed by quantitative real-time PCR (qrt-PCR) in 317
      primary breast cancer patients and correlated with clinical outcome data. Results
      were validated subsequently using two previously published and publicly available
      microarray data sets with different patient populations comprising 295 and 286
      breast cancer samples, respectively. RESULTS: Of the 60 genes measured by qrt
      PCR, urokinase-type plasminogen activator (uPA or PLAU) mRNA expression was the
      most significant marker associated with distant metastasis-free survival (MFS) by
      univariate Cox analysis in patients with ErbB2-positive tumors and an independent
      factor in multivariate analysis. Subsequent validation in two microarray data
      sets confirmed the prognostic value of uPA in ErbB2-positive tumors by both
      univariate and multivariate analysis. uPA mRNA expression was not significantly
      associated with MFS in ErbB2-negative tumors. Kaplan-Meier analysis showed in all
      three study populations that patients with ErbB2-positive/uPA-positive tumors
      exhibited significantly reduced MFS (hazard ratios [HR], 4.3; 95% CI, 1.6 to
      11.8; HR, 2.7; 95% CI, 1.2 to 6.2; and, HR, 2.8; 95% CI, 1.1 to 7.1; all P < .02)
      as compared with the group with ErbB2-positive/uPA-negative tumors who exhibited
      similar outcome to those with ErbB2-negative tumors, irrespective of uPA status.
      CONCLUSION: After evaluation of 898 breast cancer patients, uPA mRNA expression
      emerged as a powerful prognostic indicator in ErbB2-positive tumors. These
      results were consistent among three independent study populations assayed by
      different techniques, including qrt-PCR and two microarray platforms.

PMID- 16963729
TI  - Prediction of breast tumor progression by integrity of free circulating DNA in
      serum.
AB  - PURPOSE: Cell-free DNA circulating in serum is a candidate molecular biomarker
      for malignant tumors. Unlike uniformly truncated DNA released from apoptotic
      cells, DNA released from dead cancer cells varies in size. Serum DNA integrity,
      the ratio of longer fragments to total DNA, may be clinically useful for
      detecting breast cancer progression. PATIENTS AND METHODS: Serum samples from 51
      healthy females and 83 females with primary breast cancers (eight American Joint
      Committee on Cancer stage 0, 24 stage I, 27 stage II, 21 stage III, and three
      stage IV) were assessed preoperatively. Serum DNA integrity was assessed by
      fragment length-dependent quantitative real-time polymerase chain reaction of ALU
      DNA repeats. RESULTS: Mean serum DNA integrity was significantly higher in
      patients with stage II, III, and IV breast cancers than in healthy females (P =
      .005, P < .0001, and P = .002, respectively). The receiver operating
      characteristic (ROC) curve for discriminating patients with stage II or more
      advanced breast cancers from healthy females had an area under the curve (AUC) of
      0.79 (95% CI, 0.70 to 0.86). Mean serum DNA integrity was positively correlated
      to size of invasive cancers (r = 0.48; P < .0001) and significantly higher in the
      presence of lymphovascular invasion (LVI; 0.25 +/- 0.02 v 0.17 +/- 0.02; P <
      .0001) or lymph node (LN) metastasis (0.27 +/- 0.02 v 0.14 +/- 0.02; P < .0001).
      The ROC curve for discriminating LN metastasis had an AUC of 0.81 (95% CI, 0.72
      to 0.89). Serum DNA integrity and LVI were significant for predicting LN
      metastasis in a multivariate analysis (P = .0002 and P < .0001, respectively).
      CONCLUSION: Integrity of serum circulating DNA is a promising molecular biomarker
      for detecting breast cancer tumor progression and regional LN metastases.

PMID- 16963730
TI  - Surgical mortality in patients with esophageal cancer: development and validation
      of a simple risk score.
AB  - PURPOSE: Surgery has curative potential in a proportion of patients with
      esophageal cancer, but is associated with considerable perioperative risks. We
      aimed to develop and validate a simple risk score for surgical mortality that
      could be applied to administrative data. PATIENTS AND METHODS: We analyzed 3,592
      esophagectomy patients from four cohorts. We applied logistic regression analysis
      to predict mortality occurring within 30 days after esophagectomy for 1,327
      esophageal cancer patients older than 65 years of age, diagnosed between 1991 and
      1996 in the linked Surveillance, Epidemiology and End Results (SEER)--Medicare
      database. A simple score chart for preoperative risk assessment of surgical
      mortality was developed and validated on three other cohorts, including 714 SEER
      Medicare patients diagnosed between 1997 and 1999, 349 patients from a population
      based registry in the Netherlands diagnosed between 1993 and 2001, and 1,202
      patients from a referral hospital in the Netherlands diagnosed between 1980 and
      2002. RESULTS: Surgical mortality in the four cohorts was 11% (147 of 1,327), 10%
      (74 of 714), 7% (25 of 349), and 4% (45 of 1,202), respectively. Predictive
      patient characteristics included age, comorbidity (cardiac, pulmonary, renal,
      hepatic, and diabetes), preoperative radiotherapy or combined chemoradiotherapy,
      and a relatively low hospital volume. At validation, the simple score showed good
      agreement of predicted risks with observed mortality rates (calibration), but low
      discrimination (area under the receiver operating characteristic curve 0.58 to
      0.66). CONCLUSION: A simple risk score combining clinical characteristics along
      with hospital volume to predict surgical mortality after esophagectomy from
      administrative data may form a basis for risk adjustment in quality of care
      assessment.

PMID- 16963732
TI  - Prognostic factors in adenocarcinoma of the esophagus or gastroesophageal
      junction.
AB  - The incidence of adenocarcinoma of the esophagus is rising rapidly in Western
      Europe and North America. It is an aggressive disease with early lymphatic and
      hematogenous dissemination. TNM cancer staging systems predict survival on the
      basis of the anatomic extent of the tumor. However, the adequacy of the current
      TNM staging system for adenocarcinoma of the esophagus or gastroesophageal
      junction (GEJ) is questioned repeatedly. Numerous prognostic factors have been
      described, but are not included in the TNM system. This review describes clinical
      parameters, aspects of operative technique, response to preoperative
      chemoradiotherapy therapy, complications and established pathologic determinants
      found in the resection specimen that have a prognostic impact. Furthermore, their
      potential application in the clinical setting in patients with adenocarcinoma of
      the esophagus or GEJ is discussed. Future directions to improve staging systems
      are given.

PMID- 16963731
TI  - Pharmacodynamic studies of gefitinib in tumor biopsy specimens from patients with
      advanced gastric carcinoma.
AB  - PURPOSE: Epidermal growth factor receptor (EGFR) is highly expressed in some
      gastric cancers and is implicated in cancer cell growth and proliferation. The
      objective of this study was to assess the in situ biologic activity of the EGFR
      tyrosine kinase inhibitor gefitinib in gastric tumor samples in a phase II study.
      METHODS: Patients with previously treated stage IV adenocarcinoma of the stomach
      or gastroesophageal junction were randomly assigned to receive gefitinib (250 or
      500 mg/d). Tumor biopsies, obtained at screening and on day 28 of treatment, were
      assessed for biomarker expression using immunohistochemistry and analysis of
      apoptosis. RESULTS: One hundred sixteen tumor samples from 70 patients were
      available, 70 were baseline and 46 were on-therapy biopsies. At baseline, levels
      of EGFR expression significantly correlated with levels of phosphorylated EGFR
      (pEGFR; P < .001) and Ki67 expression (P = .011), but not with phosphorylated
      mitogen-activated protein kinase (pMAPK). After gefitinib treatment, levels of
      pEGFR in tumor cells were significantly reduced (P = .001); this was not the case
      for pMAPK and phosphorylated Akt (pAkt). However, in some cases gefitinib
      inhibited pAkt and these tumors had enhanced apoptosis. Likewise, there was a
      significant correlation between increased exposure to geftinib and enhanced
      apoptosis. CONCLUSION: Gefitinib reached the tumors at concentrations sufficient
      to inhibit EGFR activation in advanced gastric carcinoma patients, although this
      did not translate into clinical benefit. Overall, intratumoral phosphorylation of
      MAPK and Akt was not significantly inhibited by gefitinib. However, the finding
      that decreases in pAkt correlated with enhanced apoptosis deserves further
      exploration.

PMID- 16963733
TI  - Is there a role for SV40 in human cancer?
AB  - The question of whether Simian Virus 40 (SV40) can cause human tumors has been
      one of the most highly controversial topics in cancer research during the last 50
      years. The longstanding debate began with the discovery of SV40 as a contaminant
      in poliovirus vaccine stocks that were used to inoculate approximately 100
      million children and adults in the United States between 1955 and 1963, and
      countless more throughout the world. Concerns regarding the potential health risk
      of SV40 exposure were reinforced by studies demonstrating SV40's potential to
      transform human cells and promote tumor growth in animal models. Many studies
      have attempted to assess the relationship between the potential exposure of
      humans to SV40 and cancer incidence. Reports of the detection of SV40 DNA in a
      variety of cancers have raised serious concerns as to whether the inadvertent
      inoculation with SV40 has led to the development of cancer in humans. However,
      inconsistent reports linking SV40 with various tumor types has led to conflicting
      views regarding the potential of SV40 as a human cancer virus. Several recent
      studies suggest that older detection methodologies were flawed, and the
      limitations of these methods could account for most, if not all, of the positive
      correlations of SV40 in human tumors to date. Although many people may have been
      exposed to SV40 by polio vaccination, there is inadequate evidence to support
      widespread SV40 infection in the population, increased tumor incidence in those
      individuals who received contaminated vaccine, or a direct role for SV40 in human
      cancer.

PMID- 16963734
TI  - Flavivirus membrane fusion.
AB  - Flavivirus membrane fusion is mediated by a class II viral fusion protein, the
      major envelope protein E, and the fusion process is extremely fast and efficient.
      Understanding of the underlying mechanisms has been advanced significantly by the
      determination of E protein structures in their pre- and post-fusion conformations
      and by the elucidation of the quarternary organization of E proteins in the viral
      envelope. In this review, these structural data are discussed in the context of
      functional and biochemical analyses of the flavivirus fusion mechanism and its
      characteristics are compared with those of other class II- and class I-driven
      fusion processes.

PMID- 16963735
TI  - Measles virus: cellular receptors, tropism and pathogenesis.
AB  - Measles virus (MV), a member of the genus Morbillivirus in the family
      Paramyxoviridae, is an enveloped virus with a non-segmented, negative-strand RNA
      genome. It has two envelope glycoproteins, the haemagglutinin (H) and fusion
      proteins, which are responsible for attachment and membrane fusion, respectively.
      Human signalling lymphocyte activation molecule (SLAM; also called CD150), a
      membrane glycoprotein of the immunoglobulin superfamily, acts as a cellular
      receptor for MV. SLAM is expressed on immature thymocytes, activated lymphocytes,
      macrophages and dendritic cells and regulates production of interleukin (IL)-4
      and IL-13 by CD4+ T cells, as well as production of IL-12, tumour necrosis factor
      alpha and nitric oxide by macrophages. The distribution of SLAM is in accord with
      the lymphotropism and immunosuppressive nature of MV. Canine distemper virus and
      Rinderpest virus, other members of the genus Morbillivirus, also use canine and
      bovine SLAM as receptors, respectively. Laboratory-adapted MV strains may use the
      ubiquitously expressed CD46, a complement-regulatory molecule, as an alternative
      receptor through amino acid substitutions in the H protein. Furthermore, MV can
      infect SLAM- cells, albeit inefficiently, via the SLAM- and CD46-independent
      pathway, which may account for MV infection of epithelial, endothelial and
      neuronal cells in vivo. MV infection, however, is not determined entirely by the
      H protein-receptor interaction, and other MV proteins can also contribute to its
      efficient growth by facilitating virus replication at post-entry steps.
      Identification of SLAM as the principal receptor for MV has provided us with an
      important clue for better understanding of MV tropism and pathogenesis.

PMID- 16963736
TI  - Endotheliotropic elephant herpesvirus, the first betaherpesvirus with a thymidine
      kinase gene.
AB  - Endotheliotropic elephant herpesvirus (elephantid herpesvirus 1; ElHV-1) is
      apathogenic for African elephants (Loxodonta africana), but causes fatal
      haemorrhagic disease in Asian elephants (Elephas maximus). This is thought to
      occur through transmission from African elephants in places where both species
      are housed, such as zoological gardens. The virus has caused considerable losses
      in North American and European zoological gardens and thus severely impedes
      breeding of the endangered Asian elephant. Previously, the ultrastructural and
      genetic characterization of ElHV-1 from a male Asian elephant that died from the
      disease at the Berlin zoological gardens in 1998 have been reported. Here, a
      partial characterization of the ElHV-1 genome is presented. A 60 kbp locus,
      spanning 34 open reading frames, was analysed. Most of the detected genes were
      found to be conserved among the herpesviruses and showed an overall arrangement
      most similar to that of betaherpesviruses, in particular Human herpesvirus 6 and
      Human herpesvirus 7. Most importantly, in addition to a protein kinase gene that
      is homologous to the human cytomegalovirus UL97 gene, a thymidine kinase (TK)
      gene was found, which is generally missing in betaherpesvirus genomes. Thus, ElHV
      1 is the only known betaherpesvirus to encode a TK gene. This peculiarity might
      contribute to the fulminant pathogenicity of ElHV-1, but also provide a crucial
      enzymic activity for developing an efficient antiviral therapy with currently
      available nucleoside analogues.

PMID- 16963737
TI  - Virulence attenuation of Dengue virus due to augmented glycosaminoglycan-binding
      affinity and restriction in extraneural dissemination.
AB  - To gain insight into the role of cell surface glycosaminoglycans (GAG) in dengue
      virus (DEN) cell tropism and virulence, DEN-2 mouse brain-adapted vaccine
      candidate, neurovirulent prototype strain (NGC) and low-passage strain, PUO-218,
      were passaged in BHK-21 and SW13 cells to isolate variants with high affinity for
      GAG. Sequence comparisons of parent and passage variants revealed five GAG
      binding determinants, which all cluster in a surface-exposed region in domain II
      of the three-dimensional structure of the DEN envelope protein. Using an
      infectious cDNA clone of NGC and an NGC/PUO-218 prM-E chimeric clone, it was
      demonstrated that the GAG-binding determinants augment the specific infectivity
      for BHK-21 and/or SW13 cells by 10- to 170-fold and in some cases marginally
      reduce that for Vero cells. This altered cell tropism was due to a greater
      dependence of the variants on cell surface GAG for attachment/entry, given their
      increased susceptibility to heparin inhibition. The effect of the GAG-binding
      determinants on virulence was examined in mice deficient in alpha/beta/gamma
      interferon responses. High GAG affinity strongly correlated with low
      neuroinvasiveness due to rapid virus clearance from the blood. It was speculated
      that this mechanism accounts for the attenuation in primates of some DEN vaccine
      candidates. Interestingly, the GAG-binding variants did not display marked
      attenuation of neurovirulence and the opposing effect of enhanced neurovirulence
      was associated with one determinant (Lys126) already present in mouse brain
      adapted NGC. This discrepancy of attenuated neuroinvasiveness and augmented
      neurovirulence may be reconciled by the existence of different mechanisms of
      virus dissemination in the brain and in extraneural tissues.

PMID- 16963738
TI  - Genotype turnover by reassortment of replication complex genes from avian
      influenza A virus.
AB  - Reassortment among the RNA segments of Influenza A virus caused the two most
      recent human influenza pandemics; recently, reassortment has generated viral
      genotypes associated with outbreaks of avian H5N1 influenza in Asia and Europe. A
      statistical analysis has been developed for the systematic identification and
      characterization of reassortant viruses. The analysis was applied to the genes of
      the replication complex of 152 avian influenza A viruses isolated between 1966
      and 2004 from predominantly terrestrial and domestic aquatic avian species. The
      results indicated that reassortment among these genes was pervasive throughout
      this period and throughout both the Eurasian and North American lineages of the
      virus. Evidence is presented that the circulating genotypes of the replication
      complex are being replaced continually by novel genotypes created by
      reassortment. No constraints for coordinated reassortment among genes of the
      replication complex were evident; rather, reassortment almost always proceeded
      one segment at a time. A maximum-likelihood estimate of the rate of reassortment
      was derived. For significantly diverged Asian avian influenza A viruses from the
      period 1991-2004, it was estimated that the median duration between creation of a
      new genotype and its next segment reassortment was 3 years. Reassortments that
      introduced previously unobserved influenza genetic material were detected. These
      findings point to substantial potential for rapid generation of novel avian
      influenza A viruses, emphasizing the importance of intensive surveillance of
      these host species in preparation for a possible pandemic.

PMID- 16963739
TI  - Herpes simplex virus type 1 ICP0 localizes in the stromal layer of infected
      rabbit corneas and resides predominantly in the cytoplasm and/or perinuclear
      region of rabbit keratocytes.
AB  - Herpes stromal keratitis (HSK) results from the reactivation of herpes simplex
      virus type-1 (HSV-1) in the cornea. The subsequent corneal inflammation and
      neovascularization may lead to scarring and visual loss. The cellular and
      molecular mechanisms underlying HSK remain unknown. The presence of stromal HSV-1
      viral proteins or antigens in the HSK cornea remains a subject of debate. It was
      recently reported that HSV-1 ICP0 rapidly diffuses out of infected rabbit
      corneas. To investigate further the presence of HSV-1 ICP0 in the infected
      cornea, particularly in the corneal stroma, ex vivo confocal microscopy was used
      to scan rabbit corneas infected with the virus ICP0-EYFP, an HSV-1 derivative
      (strain 17+) that expresses ICP0 fused to the enhanced yellow fluorescent protein
      (EYFP). These results demonstrate that ICP0 is expressed in the corneal
      epithelium and stromal cells (keratocytes) of infected rabbit corneas throughout
      acute infection. Furthermore, expression of ICP0-EYFP appears localized to
      punctate, granular deposits within stromal keratocytes, showing both a
      cytoplasmic and perinuclear localization. These findings provide new data
      demonstrating that anterior corneal keratocytes become infected and express ICP0
      during acute HSV-1 infection.

PMID- 16963740
TI  - Neurotropism of herpes simplex virus type 1 in brain organ cultures.
AB  - The mechanism of herpes simplex virus type 1 (HSV-1) penetration into the brain
      and its predilection to infect certain neuronal regions is unknown. In order to
      study HSV-1 neurotropism, an ex vivo system of mice organotypic brain slices was
      established and the tissue was infected with HSV-1 vectors. Neonate tissues
      showed restricted infection confined to leptomeningeal, periventricular and
      cortical brain regions. The hippocampus was the primary parenchymatous structure
      that was also infected. Infection was localized to early progenitor and ependymal
      cells. Increasing viral inoculum increased the intensity and enlarged the
      infected territory, but the distinctive pattern of infection was maintained and
      differed from that observed with adenovirus and Vaccinia virus. Neonate brain
      tissues were much more permissive for HSV-1 infection than adult mouse brain
      tissues. Taken together, these results indicate a complex interaction of HSV-1
      with different brain-cell types and provide a useful vehicle to elucidate the
      mechanisms of viral neurotropism.

PMID- 16963741
TI  - Glycoprotein G is a virulence factor in infectious laryngotracheitis virus.
AB  - Infectious laryngotracheitis virus (ILTV; Gallid herpesvirus 1) is an
      alphaherpesvirus that causes acute respiratory disease in chickens. The role of
      glycoprotein G (gG) in vitro has been investigated in a number of
      alphaherpesviruses, but the relevance of gG in vivo in the pathogenicity of ILTV
      or in other alphaherpesviruses is unknown. In this study, gG-deficient mutants of
      ILTV were generated and inoculated into specific-pathogen-free chickens to assess
      the role of gG in pathogenicity. In chickens, gG-deficient ILTV reached a similar
      titre to wild-type (wt) ILTV but was significantly attenuated with respect to
      induction of clinical signs, effect on weight gain and bird mortality. In
      addition, an increased tracheal mucosal thickness, reflecting increased
      inflammatory cell infiltration at the site of infection, was detected in birds
      inoculated with gG-deficient ILTV compared with birds inoculated with wt ILTV.
      The reinsertion of gG into gG-deficient ILTV restored the in vivo phenotype of
      the mutant to that of wt ILTV. Quantitative PCR analysis of the expression of the
      genes adjacent to gG demonstrated that they were not affected by the deletion of
      gG and investigations in vitro confirmed that the phenotype of gG-deficient ILTV
      was consistent with unaltered expression of these adjacent genes. This is the
      first reported study to demonstrate definitively that gG is a virulence factor in
      ILTV and that deletion of gG from this alphaherpesvirus genome causes marked
      attenuation of the virus in its natural host.

PMID- 16963742
TI  - Human cytomegalovirus-induced reduction of extracellular matrix proteins in
      vascular smooth muscle cell cultures: a pathomechanism in vasculopathies?
AB  - Human cytomegalovirus (HCMV) infection appears to be linked to the pathogenesis
      of atherosclerosis. An association between HCMV infection and an enhanced
      restenosis rate as well as the induction of vasculopathies after solid organ
      transplantation has been documented. Knowledge of the cellular and molecular
      basis of these findings is limited, however. By Northern blot and RT-PCR analysis
      of human foreskin fibroblasts (HFF) and human coronary artery smooth muscle cells
      (SMC), we identified extracellular matrix (ECM) genes that were downregulated
      after HCMV infection, including collagen type I and fibronectin. Quantitative
      immunoassays showed a significant reduction of soluble collagen type I and
      fibronectin proteins in supernatants of both cell types. This was shown to be a
      direct effect of HCMV infection and not due to a response to interferons released
      from infected cells, since neutralization of alpha and beta interferon activity
      could not block virus-induced downregulation of matrix proteins. As the amount of
      ECM depends on both synthesis and degradation, we also assessed the influence of
      HCMV on the activity of matrix metalloproteinases (MMP). Interestingly, a
      significant difference in virus-induced matrix degradation could be shown between
      the two cell types. HCMV upregulated MMP-2 protein and activity in SMC but not in
      HFF. Thus, HCMV infection of SMC reduces ECM dramatically by inducing two
      independent mechanisms that influence synthesis as well as degradation of ECM.
      These may represent molecular mechanisms for HCMV-induced pathogenesis of
      inflammatory vasculopathies and may facilitate dissemination of HCMV by promoting
      the detachment of infected cells in vivo.

PMID- 16963743
TI  - Cell target genes of Epstein-Barr virus transcription factor EBNA-2: induction of
      the p55alpha regulatory subunit of PI3-kinase and its role in survival of EREB2.5
      cells.
AB  - Microarray analysis covering most of the annotated RNAs in the human genome
      identified a panel of genes induced by the Epstein-Barr virus (EBV) EBNA-2
      transcription factor in the EREB2.5 human B-lymphoblastoid cell line without the
      need for any intermediate protein synthesis. Previous data indicating that PIK3R1
      RNA (the alpha regulatory subunit of PI3-kinase) was induced were confirmed, but
      it is now shown that it is the p55alpha regulatory subunit that is induced.
      Several EBV-immortalized lymphoblastoid cell lines were shown to express
      p55alpha. Expression of PI3-kinase p85 regulatory and p110 catalytic subunits was
      not regulated by EBNA-2. Proliferation of EREB2.5 lymphoblastoid cells was
      inhibited by RNAi knock-down of p55alpha protein expression, loss of p55alpha
      being accompanied by an increase in apoptosis. p55alpha is thus a functional
      target of EBNA2 in EREB2.5 cells and the specific regulation of p55alpha by EBV
      will provide an opportunity to investigate the physiological function of p55alpha
      in this human cell line.

PMID- 16963744
TI  - Human cellular protein VRK2 interacts specifically with Epstein-Barr virus BHRF1,
      a homologue of Bcl-2, and enhances cell survival.
AB  - BHRF1, an early gene product of Epstein-Barr virus (EBV), is structurally and
      functionally homologous to Bcl-2, a cellular anti-apoptotic protein. BHRF1 has
      been shown to protect cells from apoptosis induced by numerous external stimuli.
      Nasopharyngeal carcinoma is an epithelial cancer associated closely with EBV
      infection. Specific proteins that might interact with and modulate the BHRF1 anti
      apoptotic activity in normal epithelial cells are of interest. Therefore, a cDNA
      library derived from normal human foreskin keratinocytes was screened by the
      yeast two-hybrid system and a cellular gene encoding human vaccinia virus B1R
      kinase-related kinase 2 (VRK2) was isolated. Interaction between the cellular
      VRK2 and viral BHRF1 proteins was further demonstrated by glutathione S
      transferase pull-down assays, confocal laser-scanning microscopy and co
      immunoprecipitation. Analyses of VRK2-deletion mutants revealed that a 108 aa
      fragment at the C terminus was important for VRK2 to interact with BHRF1. For
      BHRF1, aa 1-18 and 89-142 were crucial in interacting with VRK2 and these two
      regions are counterparts of Bcl-2 homology domains 4 and 1. Overexpressed VRK2
      alone showed a modest effect in anti-apoptosis and appeared to enhance cell
      survival in the presence of BHRF1. However, this enhancement was not observed
      when VRK2 was co-expressed with Bcl-2. The results indicate that human VRK2
      interacts specifically with EBV BHRF1 and that the interaction is involved in
      protecting cells from apoptosis.

PMID- 16963745
TI  - Epstein-Barr virus nuclear antigen 3A contains six nuclear-localization signals.
AB  - The Epstein-Barr nuclear antigen 3A (EBNA3A) is one of only six viral proteins
      essential for Epstein-Barr virus-induced transformation of primary human B cells
      in vitro. Viral proteins such as EBNA3A are able to interact with cellular
      proteins, manipulating various biochemical and signalling pathways to initiate
      and maintain the transformed state of infected cells. EBNA3A has been reported to
      have one nuclear-localization signal and is targeted to the nucleus during
      transformation, where it associates with components of the nuclear matrix. By
      using enhanced green fluorescent protein-tagged deletion mutants of EBNA3A in
      combination with site-directed mutagenesis, an additional five functional nuclear
      localization signals have been identified in the EBNA3A protein. Two of these (aa
      63-66 and 375-381) were computer-predicted, whilst the remaining three (aa 394
      398, 573-578 and 598-603) were defined functionally in this study.

PMID- 16963746
TI  - Analysis of Epstein-Barr virus latent gene expression in endemic Burkitt's
      lymphoma and nasopharyngeal carcinoma tumour cells by using quantitative real
      time PCR assays.
AB  - Studies of Epstein-Barr virus (EBV)-positive cell lines have identified several
      forms of virus latency, but the patterns of virus gene expression in EBV-positive
      tumour cells appear more variable. However, it is unclear to what extent these
      differences merely reflect the increased sensitivities of different detection
      methods. Here, the design and validation of novel real-time RT-PCR assays to
      quantify relative levels of EBV transcripts are described. When the new assays
      were used to screen a collection of endemic Burkitt's lymphoma tumours, abundant
      Qp-driven EBNA1 expression was found, whereas the other latent transcripts (with
      the exception of LMP2A) were either absent or detectable only at trace levels.
      Analysis of 12 nasopharyngeal carcinoma biopsies revealed significant levels of
      EBNA1 and LMP2A transcripts in almost every case but, in contrast to previous
      reports, LMP1 expression was undetectable. These new quantitative assays may help
      to provide a clearer picture of EBV gene expression in tumour material.

PMID- 16963747
TI  - Generation of a novel replication-incompetent adenoviral vector derived from
      human adenovirus type 49: manufacture on PER.C6 cells, tropism and
      immunogenicity.
AB  - Recombinant adenoviral vectors based on type 5 (rAd5) show great promise as a
      vaccine carrier. However, neutralizing activity against Ad5 is prevalent and high
      titred among human populations, and significantly dampens Ad5-based vaccine
      modalities. The generation of alternative adenoviral vectors with low
      seroprevalence thus receives much research attention. Here, it is shown that a
      member from human adenovirus subgroup D, i.e. Ad49, does not cross-react with Ad5
      neutralizing activity, making it a candidate serotype for vector development.
      Therefore, a plasmid system that allows formation of replication-incompetent
      adenovirus serotype 49 vaccine vectors (rAd49) was constructed and it was
      demonstrated that rAd49 can be successfully propagated to high titres on existing
      Ad5.E1-complementing cell lines such as PER.C6. Using an rAd49 vector carrying
      the luciferase marker gene, detailed seroprevalence studies were performed,
      demonstrating that rAd49 has low seroprevalence and neutralizing antibody titres
      worldwide. Also, we have initiated rAd49 vector receptor usage suggesting that
      rAd49 utilizes hCD46 as a cellular receptor. Finally, the immunogenicity of the
      rAd49 vector was assessed and it was shown that an rAd49.SIVGag vaccine induces
      strong anti-SIVGag CD8+ T-lymphocytes in naive mice, albeit less than an
      rAd5.SIVGag vaccine. However, in mice with high anti-Ad5 immunity the rAd5.SIVGag
      vaccine was severely blunted, whereas the anti-SIVGag response was not
      significantly suppressed using the rAd49.SIVGag vaccine. These data demonstrate
      the potential of a replication deficient human group D adenoviral vector for
      vaccination purposes.

PMID- 16963748
TI  - Development of the dodecahedral penton particle from adenovirus 3 for therapeutic
      application.
AB  - The subviral dodecahedral particle of adenovirus 3, which assembles spontaneously
      in insect cells expressing the viral penton base protein, shows promise as a
      vector for drug delivery. Its ability to gain cell entry has been demonstrated
      and recent structural analysis has outlined details of the interfaces between
      penton bases and the importance of proteolysis of the penton base N terminus for
      assembly, providing a basis for understanding particle assembly and stability.
      Here, work in manipulating the assembly status of the dodecahedron by changing
      buffer conditions and subsequent success in passively encapsidating a marker
      molecule is described. This represents an important stage towards development of
      the dodecahedral particle for use as a delivery vehicle capable of targeting
      therapeutic molecules to specific cell types.

PMID- 16963749
TI  - Temporal and differential gene expression of Singapore grouper iridovirus.
AB  - Singapore grouper iridovirus (SGIV), an iridovirus in the genus Ranavirus, is a
      major pathogen that results in significant economic losses in grouper
      aquaculture. To investigate further its infective mechanisms, for the first time,
      a viral DNA microarray was generated for the SGIV genome to measure the
      expression of its predicted open reading frames simultaneously in vitro. By using
      the viral DNA microarray, the temporal gene expression of SGIV was characterized
      and the DNA microarray data were consistent with the results of real-time RT-PCR
      studies. Furthermore, different-stage viral genes (i.e. immediate-early, early
      and late genes) of SGIV were uncovered by combining drug treatments and DNA
      microarray studies. These results should offer important insights into the
      replication and pathogenesis of iridoviruses.

PMID- 16963750
TI  - Short-term, but not post-exposure, protection against lethal orthopoxvirus
      challenge after immunization with modified vaccinia virus Ankara.
AB  - Safety-tested vaccinia virus (VACV) MVA serves as a candidate third-generation
      vaccine against smallpox. Here, MVA immunization of mice shortly before or after
      lethal respiratory challenge with VACV Western Reserve was investigated. Whilst
      post-exposure treatment failed to protect animals, immunizations on day 2 prior
      to challenge were fully protective. On the day of challenge, MVA inoculation may
      prevent death, but not onset of severe respiratory disease. After intranasal MVA
      application, massive influx of leukocytes (such as neutrophils, macrophages,
      natural killer cells and T cells) was found in the lungs of the animals,
      indicating the contribution of innate responses to protection. Correspondingly,
      in RAG-1-/- mice, MVA inoculation delayed onset of disease significantly, but did
      not prevent fatal infection. Thus, short-term protection required a tight
      interplay of both innate and adaptive antiviral immunity. These data suggest
      that, in addition to conventional vaccination, MVA may serve for potent emergency
      prophylaxis against orthopoxvirus infection.

PMID- 16963751
TI  - Genetic and experimental comparison of porcine circovirus type 2 (PCV2) isolates
      from cases with and without PCV2-associated lesions provides evidence for
      differences in virulence.
AB  - There are marked differences in the clinical expression of diseases associated
      with porcine circovirus type 2 (PCV2) in the field. The objective of this study
      was to compare the sequences and pathogenicity of PCV2 isolates from field cases
      with and without PCV2-associated lesions. Forty-two specific-pathogen-free (SPF)
      pigs were assigned randomly to three groups of 14 pigs each. At 7 weeks of age,
      group 1 pigs were mock-inoculated with saline, group 2 pigs were inoculated with
      PCV2-4838 (isolated from a pig with no evidence of PCV2-associated lymphoid
      lesions) and group 3 pigs were inoculated with PCV2-40895 (isolated from a pig
      with PCV2-associated lymphoid lesions and disease). The PCV2-4838 and PCV2-40895
      isolates shared approximately 98.9 % nucleotide sequence identity across the
      entire genome. A total of nine amino acid changes in ORF2 and two amino acid
      changes in ORF1 were identified between the two isolates. PCV2-4838-inoculated
      pigs had significantly more genomic copy numbers of PCV2 in their sera at 7 days
      post-inoculation (p.i.) (P<0.0001) and significantly fewer genomic copy numbers
      at 14, 21 and 28 days p.i. (P<0.05) compared with pigs inoculated with the PCV2
      40895 isolate. Microscopic lesions in lymphoid tissues were significantly less
      severe (P<0.05) and the amount of PCV2 antigen associated with these lesions was
      significantly lower (P<0.05) in pigs inoculated with PCV2-4838. The results of
      this study suggest that PCV2 isolates from the USA differ in virulence in an SPF
      pig model.

PMID- 16963752
TI  - Anti-neoplastic effect of chicken anemia virus VP3 protein (apoptin) in Rous
      sarcoma virus-induced tumours in chicken.
AB  - The anti-neoplastic effect of chicken anemia virus VP3 protein (apoptin) was
      investigated in vitro in Rous sarcoma virus (RSV)-transformed chicken embryo
      fibroblast (CEF) cells and in RSV-induced tumours of specific-pathogen-free (SPF)
      chicks in vivo. The apoptin gene was cloned in the pVAX expression vector and in
      vitro expression of the recombinant vector pVAX-CAV-VP3 was confirmed. Two groups
      of SPF chicks, each containing ten chicks, were used. Chicks in groups I and II
      were inoculated with RSV at 1 day old. Group I served as the control, receiving
      pVAX vector without insert, and group II received recombinant vector pVAX-CAV-VP3
      containing the apoptin gene, on day 10. An in vitro study confirmed that apoptin
      induced apoptosis in RSV-transformed CEF cells, which was demonstrated by
      observation of the characteristic changes of apoptosis using the indirect
      immunofluorescence technique and acridine orange/ethidium bromide staining. In
      vivo study also indicated that apoptin induced apoptosis and caused tumour
      regression by an intratumoral-delivery method. Apoptotic changes, such as nuclear
      condensation, fragmentation of the chromatin and formation of apoptic bodies in
      the tumour cells, were demonstrated by histopathology and acridine
      orange/ethidium bromide staining. No apoptotic changes were seen in the tumours
      of the control group. The results of the present study showed that apoptin had an
      anti-neoplastic effect in vivo and in vitro in RSV-induced tumours. The anti
      neoplastic effect is due to apoptin-induced apoptosis. Further improvements in
      the dose, delivery method and delivery frequency of the apoptin-expressing
      recombinant vector could help to develop apoptin as an anti-neoplastic drug.

PMID- 16963753
TI  - Phylogenetic analysis of human parvovirus B19, indicating two subgroups of
      genotype 1 in Vietnamese patients.
AB  - Recently, three distinct genotypes (1, 2 and 3) of human parvovirus B19 (B19)
      have been identified. However, the characteristics and distribution of B19
      genotypes in Vietnam have not been investigated. Phylogenetic analysis using 49
      subgenomic NS1/VP1u regions and two coding NS1-VP1/VP2 regions has been applied
      to investigate the prevalence of B19 genotypes in Vietnamese patients co-infected
      with Hepatitis B virus. Genetic analysis of the subgenomic NS1/VP1u region of B19
      revealed that two genotypes of B19 were identified in these populations, with
      predominance of genotype 1 (47/49, 96 %) followed by genotype 2 (2/49, 4 %), but
      not genotype 3. Further, phylogenetic analysis of subgenomic B19 genomes revealed
      two major subgroups within genotype 1 (B19-1A and B19-1B) with an estimated
      nucleotide difference of >5 % between each subgroup, forming different branches.
      The mean percentage of amino acid variation between subgroup B19-1A and B19-1B
      was >2 % of the NS1, VP1 and VP2 proteins. Our results indicated that two of the
      three known genotypes of B19 were present in Vietnamese patients, with genotype 1
      predominating, and that this genotype can be classified into at least two
      subgroups, B19-1A and B19-1B.

PMID- 16963754
TI  - T-cell responses to peptide fragments of the BK virus T antigen: implications for
      cross-reactivity of immune response to JC virus.
AB  - Infection with BK virus (BKV) induces both humoral and cellular immunity, but the
      viral antigens of T-antigen (T-ag) stimulating T-cell responses are largely
      unknown. To identify BKV-specific T cells in healthy individuals, peripheral
      blood lymphocytes were cultured with autologous dendritic cells (DCs) loaded with
      BKV lysate and T cells were screened for intracellular gamma interferon
      production after stimulation with an overlapping 15mer peptide library of the BKV
      T-ag. Among many immunogenic peptides identified, four T-ag peptides were
      identified as candidate major histocompatibility complex class I and II T-cell
      epitopes, restricted to human leukocyte antigen (HLA)-B*0702, -B*08, -DRB1*0301
      and -DRB1*0901. Further, a candidate 9mer peptide, LPLMRKAYL, was confirmed to be
      restricted to HLA-B*0702 and -B*08. Because the polyomaviruses BKV, JC virus
      (JCV) and Simian virus 40 (SV40) share extensive sequence similarity in the
      immunogenic proteins T-ag and VP1, it was hypothesized that, in humans, these
      proteins contain conserved cytotoxic T-lymphocyte (CTL) target epitopes. Four HLA
      restricted conserved epitopes of BKV, JCV and SV40 were identified: HLA-B*07, 
      B*08 and -DRB1*0901 for T-ag and -A*0201 for VP1. T cells cultured in vitro that
      were specific for one viral antigen recognized other conserved epitopes. CTLs
      generated from BKV T-ag and VP1 peptide were cytotoxic to DC targets pulsed with
      either BKV or JCV. Therefore, infection by one of the two viruses (BKV and JCV)
      could establish cross-immunity against the other. Although cross-cytotoxicity
      experiments were not performed with SV40, cross-recognition data from conserved
      antigen epitopes of polyomaviruses suggest strongly that cross-immunity might
      also exist among the three viruses.

PMID- 16963755
TI  - The double-stranded RNA-induced apoptosis pathway is involved in the
      cytopathogenicity of cytopathogenic Bovine viral diarrhea virus.
AB  - Bovine viral diarrhea virus (BVDV), which is classified in the genus Pestivirus,
      family Flaviviridae, can be divided into two biotypes according to its ability to
      induce a cytopathic effect in tissue culture cells. The mechanisms through which
      cytopathogenic (cp) BVDV induces cell death and non-cytopathogenic (ncp) BVDV
      causes persistent infection without producing cell death remain unclear. Here, it
      was found that the overexpression of four apoptosis-related cellular mRNAs in
      cells infected with cpBVDV could also be caused by synthetic dsRNA. In fact, it
      was found that the amount of dsRNA produced by cpBVDV considerably exceeded the
      amount yielded by ncpBVDV. To evaluate the possible involvement of dsRNA in the
      induction of apoptosis, this study examined whether RNAi-mediated depletion of
      two dsRNA-reactive cellular factors, dsRNA-dependent protein kinase and 2',5'
      oligoadenylate synthetase 1, resulted in the prevention of cpBVDV-induced
      apoptosis. Although the induction of apoptosis was reduced after the suppression
      of either factor alone, the simultaneous silencing of both factors resulted in an
      almost complete inhibition of apoptosis without affecting viral titre. These
      results showed that dsRNA is the main trigger of apoptosis in cpBVDV-infected
      cells and that the cytopathogenicity of BVDV depends on the yield potential of
      dsRNA. In contrast, ncpBVDV yielded minimal levels of dsRNA, thereby establishing
      a persistent infection without inducing apoptosis. This report supports the
      significance of viral dsRNA as a trigger of innate immune responses.

PMID- 16963756
TI  - Priming with DNA encoding E2 and boosting with E2 protein formulated with CpG
      oligodeoxynucleotides induces strong immune responses and protection from Bovine
      viral diarrhea virus in cattle.
AB  - The objective of this study was to develop an optimal vaccination strategy for
      Bovine viral diarrhea virus (BVDV). The E2 protein of BVDV plays a major
      protective role against BVDV infection. In order to be able to compare DNA,
      protein and DNA prime-protein boost regimens, a plasmid was constructed encoding
      a secreted form of the NADL strain E2 protein (pMASIA-tPAsDeltaE2). Furthermore,
      a pure secreted recombinant DeltaE2 (rDeltaE2) protein was produced. The rDeltaE2
      protein was formulated with a combination of Emulsigen and CpG
      oligodeoxynucleotide. Groups of calves were immunized with pMASIA-tPAsDeltaE2 or
      with rDeltaE2, or first with pMASIA-tPAsDeltaE2 and then with rDeltaE2. To
      evaluate the protection against BVDV, calves were challenged with BVDV strain NY
      1 after the last immunization. Although all immunized calves developed humoral
      and cellular immune responses, the antibody responses in the DNA prime-protein
      boost group were stronger than those elicited by either the DNA vaccine or the
      protein vaccine. In particular, E2-specific antibody titres were enhanced
      significantly after boosting the DeltaE2 DNA-primed calves with rDeltaE2 protein.
      Moreover, protection against BVDV challenge was obtained in the calves treated
      with the DNA prime-protein boost vaccination regimen, as shown by a significant
      reduction in weight loss, viral excretion and lymphopenia, compared with the
      unvaccinated calves and the animals immunized with the DNA or protein only. These
      results demonstrate the advantage of a DNA prime-protein boost vaccination
      approach in an outbred species.

PMID- 16963757
TI  - Preferential association of Hepatitis C virus with apolipoprotein B48-containing
      lipoproteins.
AB  - Hepatitis C virus (HCV) in cell culture has a density comparable to that of other
      members of the family Flaviviridae, whereas in vivo infectious particles are
      found partially in low-density fractions, associated with triacylglycerol (TG)
      rich lipoproteins (TRLs). In the blood of infected patients, HCV circulates as
      heterogeneous particles, among which are lipo-viroparticles (LVPs), globular
      particles rich in TG and containing viral capsid and RNA. The dual viral and
      lipoprotein nature of LVPs was addressed further with respect to apolipoprotein
      composition and post-prandial dynamic lipid changes. The TRLs exchangeable apoE, 
      CII and -CIII, but not the high-density lipoprotein apoA-II, were present on
      LVPs, as well as the viral envelope proteins. apoB100 and -B48, the two isoforms
      of the non-exchangeable apoB, were represented equally on LVPs, despite the fact
      that apoB48 was barely detectable in the plasma of these fasting patients. This
      indicates that a significant fraction of plasma HCV was associated with apoB48
      containing LVPs. Furthermore, LVPs were enriched dramatically and rapidly in
      triglycerides after a fat meal. As apoB48 is synthesized exclusively by the
      intestine, these data highlight the preferential association of HCV with
      chylomicrons, the intestine-derived TRLs. These data raise the question of the
      contribution of the intestine to the viral load and suggest that the virus could
      take advantage of TRL assembly and secretion for its own production and of TRL
      fate to be delivered to the liver.

PMID- 16963758
TI  - Role of the yellow fever virus structural protein genes in viral dissemination
      from the Aedes aegypti mosquito midgut.
AB  - Live-attenuated virus vaccines are key components in controlling arboviral
      diseases, but they must not disseminate in or be transmitted by mosquito vectors.
      Although the cycles in which many mosquito-borne viruses are transmitted are well
      understood, the role of viral genetics in these processes has not been fully
      elucidated. Yellow fever virus (YFV) is an important arbovirus and the prototype
      member of the family Flaviviridae. Here, YFV was used in Aedes aegypti mosquitoes
      as a model to investigate the genetic basis of infection and dissemination in
      mosquitoes. Viruses derived from infectious clones and chimeric viruses with
      defined sequential manipulations were used to investigate the influence of
      specific sequences within the membrane and envelope structural protein genes on
      dissemination of virus from the mosquito midgut. Substitution of domain III of
      the envelope protein from a midgut-restricted YFV into a wild-type YFV resulted
      in a marked decrease in virus dissemination, suggesting an important role for
      domain III in this process. However, synergism between elements within the
      flavivirus structural and non-structural protein genes may be necessary for
      efficient virus escape from the mosquito midgut.

PMID- 16963759
TI  - Antiviral action of nitric oxide on dengue virus type 2 replication.
AB  - Recently, nitric oxide (NO) has been shown to suppress dengue virus (DENV) RNA
      and protein accumulation in infected cells. In this report, the potential target
      of the inhibitory effect of NO was studied at the molecular level. The NO donor,
      S-nitroso-N-acetylpenicillamine (SNAP), showed an inhibitory effect on RNA
      accumulation at around 8-14 h post-infection, which corresponded to the step of
      viral RNA synthesis in the DENV life cycle. The activity of the viral replicase
      isolated from SNAP-treated DENV-2-infected cells was suppressed significantly
      compared with that of the negative-control N-acetyl-DL-penicillamine (NAP)
      treated cells. Further investigations on the molecular target of NO action showed
      that the activity of recombinant DENV-2 NS5 in negative-strand RNA synthesis was
      affected in the presence of 5 mM SNAP in in vitro RNA-dependent RNA polymerase
      (RdRp) assays, whereas the RNA helicase activity of DENV-2 NS3 was not inhibited
      up to a concentration of 15 mM SNAP. These results suggest that the inhibitory
      effect of NO on DENV infection is partly via inhibition of the RdRp activity,
      which then downregulates viral RNA synthesis.

PMID- 16963760
TI  - The 3' end of the foot-and-mouth disease virus genome establishes two distinct
      long-range RNA-RNA interactions with the 5' end region.
AB  - The untranslated regions (UTRs) of the foot-and-mouth disease virus (FMDV) genome
      contain multiple functional elements. In the 5' UTR, the internal ribosome entry
      site (IRES) element governs cap-independent translation initiation, whereas the S
      region is presumably involved in RNA replication. The 3' UTR, composed of two
      stem-loops and a poly(A) tract, is required for viral infectivity and stimulates
      IRES activity. Here, it was found that the 3' end established two distinct strand
      specific, long-range RNA-RNA interactions, one with the S region and another with
      the IRES element. These interactions were not observed with the 3' UTR of a
      different picornavirus. Several results indicated that different 3' UTR motifs
      participated in IRES or S region interactions. Firstly, a high-order structure
      adopted by both the entire IRES and the 3' UTR was essential for RNA interaction.
      In contrast, the S region interacted with each of the stem-loops. Secondly, S-3'
      UTR interaction but not IRES-3' UTR interaction was dependent on a poly(A)
      dependent conformation. However, no other complexes were observed in mixtures
      containing the three transcripts, suggesting that these regions did not interact
      simultaneously with the 3' UTR probe. Cellular proteins have been found to bind
      the S region and one of these also binds to the 3' UTR in a competitive manner.
      Our data suggest that 5'-3'-end bridging through both direct RNA-RNA contacts and
      RNA-protein interactions may play an essential role in the FMDV replication
      cycle.

PMID- 16963761
TI  - Formerly unclassified, acid-stable equine picornaviruses are a third equine
      rhinitis B virus serotype in the genus Erbovirus.
AB  - Acid-stable equine picornaviruses (ASPs) were identified as a distinct serotype
      of equine picornaviruses that were isolated from nasal swabs taken from horses
      with acute febrile respiratory disease in the UK and Japan, and were placed in
      the group of unclassified picornaviruses. The nucleotide sequence of the P1
      region, encoding the capsid proteins, was determined for three ASP isolates from
      the UK and the sequences were aligned with published sequences of Equine rhinitis
      B virus (ERBV), genus Erbovirus, including acid-labile ERBV1 and ERBV2 and the
      recently identified acid-stable ERBV1. The ASPs belong to the same phylogenetic
      group, composed of five acid-stable ERBV1 isolates. ERBV1 rabbit antiserum
      neutralized the ASP isolates at approximately 1/10 titre relative to acid-stable
      and acid-labile ERBV1 isolates, supporting prior findings that ASPs are a
      distinct serotype, albeit cross-neutralizing weakly with ERBV1. The genus
      Erbovirus therefore presently comprises three serotypes: ERBV1, ERBV2 and the
      proposed ERBV3.

PMID- 16963762
TI  - Rubella virus pseudotypes and a cell-cell fusion assay as tools for functional
      analysis of the rubella virus E2 and E1 envelope glycoproteins.
AB  - The rubivirus Rubella virus contains the two envelope glycoproteins E2 and E1 as
      a heterodimeric spike complex embedded in its lipid envelope. The functions of
      both proteins, especially of E2, in the process of viral entry are still not
      entirely understood. In order to dissect E2 and E1 entry functions from post
      entry steps, pseudotypes of lentiviral vectors based on Simian immunodeficiency
      virus were used. C-terminally modified E2 and E1 variants successfully
      pseudotyped lentiviral vector particles. This is the first report to show that
      not only E1, but also E2, is able to mediate infectious viral entry. Furthermore,
      a cell-cell fusion assay was used to further clarify membrane-fusion activities
      of E2 and E1 as one of the early steps of infection. It was demonstrated that the
      capsid protein, when coexpressed in cis, enhances the degree of E2- and E1
      mediated cell-cell fusion.

PMID- 16963763
TI  - Mutation of the Rev-binding loop in the human immunodeficiency virus 1 leader
      causes a replication defect characterized by altered RNA trafficking and
      packaging.
AB  - An internal RNA loop, located within the packaging signal of human
      immunodeficiency virus 1, that resembles the Rev-responsive element (RRE) closely
      was identified previously. Subsequent in vitro studies confirmed that the loop,
      termed loop A, could bind Rev protein specifically. Its proximity to the major
      splice donor has suggested a role for Rev-loop A interaction supplementary to or
      preceding that of the Rev-RRE interaction. To investigate this further in a
      replication-competent provirus, loop A was mutated to decrease its affinity for
      Rev. Impairing the Rev-loop A interaction led to reduced nuclear export of viral
      genomic RNA. RNA packaging decreased by approximately 30%. Viral protein
      production and export of virus particles appeared normal; however, the virus was
      severely replication-deficient. The loop A sequence, which is 98% conserved
      amongst viral isolates, is implicated in several cis-acting functions critical to
      virus viability.

PMID- 16963764
TI  - Nora virus, a persistent virus in Drosophila, defines a new picorna-like virus
      family.
AB  - Several viruses, including picornaviruses, are known to establish persistent
      infections, but the mechanisms involved are poorly understood. Here, a novel
      picorna-like virus, Nora virus, which causes a persistent infection in Drosophila
      melanogaster, is described. It has a single-stranded, positive-sense genomic RNA
      of 11879 nt, followed by a poly(A) tail. Unlike other picorna-like viruses, the
      genome has four open reading frames (ORFs). One ORF encodes a picornavirus-like
      cassette of proteins for virus replication, including an iflavirus-like RNA
      dependent RNA polymerase and a helicase that is related to those of mammalian
      picornaviruses. The three other ORFs are not closely related to any previously
      described viral sequences. The unusual sequence and genome organization in Nora
      virus suggest that it belongs to a new family of picorna-like viruses.
      Surprisingly, Nora virus could be detected in all tested D. melanogaster
      laboratory stocks, as well as in wild-caught material. The viral titres varied
      enormously, between 10(4) and 10(10) viral genomes per fly in different stocks,
      without causing obvious pathological effects. The virus was also found in
      Drosophila simulans, a close relative of D. melanogaster, but not in more
      distantly related Drosophila species. It will now be possible to use Drosophila
      genetics to study the factors that control this persistent infection.

PMID- 16963765
TI  - Genetic diversity and phylogeography of cassava mosaic viruses in Kenya.
AB  - Cassava is a major factor in food security across sub-Saharan Africa. However,
      the crop is susceptible to losses due to biotic stresses, in particular to
      viruses of the genus Begomovirus (family Geminiviridae) that cause cassava mosaic
      disease (CMD). During the 1990s, an epidemic of CMD severely hindered cassava
      production across eastern and central Africa. A significant influence on the
      appearance of virus epidemics is virus diversity. Here, a survey of the genetic
      diversity of CMD-associated begomoviruses across the major cassava-growing areas
      of Kenya is described. Because an initial PCR-restriction fragment-length
      polymorphism analysis identified a much greater diversity of viruses than assumed
      previously, representative members of the population were characterized by
      sequence analysis. The full-length sequences of 109 components (68 DNA-A and 41
      DNA-B) were determined, representing isolates of East African cassava mosaic
      virus and East African cassava mosaic Zanzibar virus, as well as a novel
      begomovirus species for which the name East African cassava mosaic Kenya virus is
      proposed. The DNA-B components were much less diverse than their corresponding
      DNA-A components, but nonetheless segregated into western and eastern (coastal)
      groups. All virus species and strains encountered showed distinct geographical
      distributions, highlighting the importance of preventing both the movement of
      viruses between these regions and the importation of the disease from adjacent
      countries and islands in the Indian Ocean that would undoubtedly encourage
      further diversification.

PMID- 16963766
TI  - Selective constraint and genetic differentiation in geographically distant barley
      yellow dwarf virus populations.
AB  - Numerous studies have documented molecular variability in plant virus
      populations, but few have assessed the relative contribution of natural selection
      and genetic drift in generating the observed pattern of diversity. To this end,
      gene function, environment and phylogenetic history were examined to observe the
      effect on genetic diversity and population structure of the PAV and PAS species
      of Barley yellow dwarf virus (family Luteoviridae). Three functional classes of
      gene were analysed: transcription-related (RdRp), structural (CP) and movement
      related (MP). The results indicate that there were no inherent differences, in
      terms of total diversity or diversity at synonymous or non-synonymous nucleotide
      sites, between functional classes of genes or populations. Rather, selective
      constraints on a gene may be more or less relaxed depending on its function and
      the phylogenetic history of the population sampled. The CP of the PAS species,
      but not the PAV species, was differentiated genetically between regions. This is
      probably due to genetic drift, as there was no evidence that any gene deviated
      from a neutral model of evolution or is under positive selection. In general, the
      MP was under considerably less functional constraint than structural or
      replication-related proteins and four positively selected codon sites were
      identified. Mutations at these sites differentiate species and geographical
      subpopulations, so presumably they have aided the virus in adaptation to its host
      environment and contributed to intra- and interspecies diversification.

PMID- 16963767
TI  - Analysis of the subgenomic RNAs and the small open reading frames of Beet black
      scorch virus.
AB  - A full-length cDNA of the genome of Beet black scorch virus (BBSV), isolate
      Ningxia, was constructed and modified by site-directed mutagenesis to permit in
      vitro transcription of mutant viral RNAs. Two subgenomic (sg) RNAs (sgRNA1 and
      sgRNA2) appeared during BBSV replication. Mutagenesis revealed that sgRNA1
      transcription was initiated at G2209 within the P82 polymerase subunit open
      reading frame (ORF) and that transcription of sgRNA2 began at G2526 within the
      nested p7b/p5' ORF. Initiation-codon shifting or premature termination of
      translation of the three ORFs (P7a, P7b and P5') encoded by sgRNA1 indicated that
      each of the genes was required for localized movement, accumulation of viral RNAs
      and formation of local lesions on the leaves of Chenopodium amaranticolor.
      Microscopic observations of the distribution of green fluorescent protein fused
      to the N-terminal portion of the capsid protein provided additional evidence that
      the P7a, P7b and P5' proteins are each required for cell-to-cell movement. In
      contrast, elimination of sgRNA2 showed that the BBSV coat protein was not
      required for viral RNA accumulation or the appearance of local lesions on C.
      amaranticolor. In addition, disruption of the small P5 ORF previously predicted
      by computer analysis to originate at the C terminus of the P82 ORF had no effect
      on disease phenotype, suggesting that this ORF may represent a cryptic, non
      essential gene. These results show that BBSV has a novel cell-to-cell movement
      protein organization that differs in size and sequence from that of other
      viruses.

PMID- 16963768
TI  - A minimal region in the NTPase/helicase domain of the TGBp1 plant virus movement
      protein is responsible for ATPase activity and cooperative RNA binding.
AB  - The TGBp1 protein, encoded in the genomes of a number of plant virus genera as
      the first gene of the 'triple gene block', possesses an NTPase/helicase domain
      characterized by seven conserved sequence motifs. It has been shown that the
      TGBp1 NTPase/helicase domain exhibits NTPase, RNA helicase and RNA-binding
      activities. In this paper, we have analysed a series of deletion and point
      mutants in the TGBp1 proteins encoded by Potato virus X (PVX, genus Potexvirus)
      and Poa semilatent virus (PSLV, genus Hordeivirus) to map functional regions
      responsible for their biochemical activities in vitro. It was found that, in both
      PVX and PSLV, the N-terminal part of the TGBp1 NTPase/helicase domain comprising
      conserved motifs I, Ia and II was sufficient for ATP hydrolysis, RNA binding and
      homologous protein-protein interactions. Point mutations in a single conserved
      basic amino acid residue upstream of motif I had little effect on the activities
      of C-terminally truncated mutants of both TGBp1 proteins. However, when
      introduced into the full-length NTPase/helicase domains, these mutations caused a
      substantial decrease in the ATPase activity of the protein, suggesting that the
      conserved basic amino acid residue upstream of motif I was required to maintain a
      reaction-competent conformation of the TGBp1 ATPase active site.

PMID- 16963769
TI  - Genetic variation of populations of Citrus psorosis virus.
AB  - Citrus psorosis virus (CPsV), the type species of genus Ophiovirus, has a
      segmented, negative-stranded RNA genome. We examined the population structure and
      genetic variation of CPsV in three coding regions located in RNAs 1, 2 and 3,
      analysing 22 isolates from Argentina, California, Florida, Italy and Spain. Most
      isolates contained a predominant sequence and some minor variants. Estimations of
      the genetic diversity and phylogenetic clustering of isolates disclosed two
      populations, one comprising isolates from Spain, Italy, Florida and California
      and the other including the Argentinean isolates. Isolate CPV-4 (from Texas)
      included for comparison was distant from both groups, suggesting that it belongs
      to a third group. The low ratio between non-synonymous and synonymous nucleotide
      substitutions indicated strong selection for amino acid sequence conservation,
      particularly in the coat protein gene. Incongruent phylogenetic relationships in
      different genomic regions suggested that exchange of genomic segments may have
      contributed to CPsV evolution.

PMID- 16963770
TI  - Peptide display on Potato virus X: molecular features of the coat protein-fused
      peptide affecting cell-to-cell and phloem movement of chimeric virus particles.
AB  - The potexvirus Potato virus X (PVX) can be modified genetically to generate
      chimeric virus particles (CVPs) carrying heterologous peptides fused to coat
      protein (CP) subunits. A spontaneous PVX mutant expressing a truncated, but
      functional, form of the CP has been isolated. With the aim of exploiting this
      virus to display peptides useful for vaccine formulations, two novel viral
      expression vectors based on pPVX201 (bearing the wild-type PVX genome) were
      constructed encoding the truncated CP. Both vectors were able to produce
      infectious virus particles in planta and were used to insert a panel of sequences
      encoding peptides of biopharmaceutical interest as N-terminal fusions to the
      truncated cp gene. The analysis of infection progression induced by the different
      constructs enabled identification of two important structural features of the
      fused peptide, namely tryptophan content and isoelectric point, critically
      affecting the formation of PVX CVPs and virus movement through the plant. These
      results are discussed in view of the rising interest in engineered plant viruses
      for development of peptide-based epitope vaccines.

PMID- 16963771
TI  - Molecular characterization of the largest mycoviral-like double-stranded RNAs
      associated with Amasya cherry disease, a disease of presumed fungal aetiology.
AB  - The sequence of the four large (L) double-stranded RNAs (dsRNAs) associated with
      Amasya cherry disease (ACD), which has a presumed fungal aetiology, is reported.
      ACD L dsRNAs 1 (5121 bp) and 2 (5047 bp) potentially encode proteins of 1628 and
      1620 aa, respectively, that are 37% identical and of unknown function. ACD L
      dsRNAs 3 (4458 bp) and 4 (4303 bp) potentially encode proteins that are 68%
      identical and contain the eight motifs conserved in RNA-dependent RNA polymerases
      (RdRp) of dsRNA mycoviruses, having highest similarity with those of members of
      the family Totiviridae. Both terminal regions share extensive conservation in all
      four RNAs, suggesting a functional relationship between them. As ACD L dsRNAs 1
      and 2 do not encode RdRps, both are probably replicated by those from either ACD
      L dsRNA 3 or 4. Partial characterization of the equivalent L dsRNAs 3 and 4
      associated with cherry chlorotic rusty spot revealed essentially identical
      sequences.

PMID- 16963772
TI  - Application of an immunocapillary electrophoresis assay to the detection of
      abnormal prion protein in brain, spleen and blood specimens from patients with
      variant Creutzfeldt-Jakob disease.
AB  - Sensitive and specific detection of abnormal prion protein in blood could provide
      a diagnostic test or screening assay for animal and human prion diseases. Here,
      the application of an immunocapillary electrophoresis (ICE) method developed for
      sheep scrapie to brain, spleen and blood from patients with Creutzfeldt-Jakob
      disease (CJD) is described. The assay involves organic-solvent extraction, a
      competitive immunoassay using fluorescently labelled synthetic prion protein
      peptides and polyclonal antibodies specific for those sequences, and analysis by
      capillary electrophoresis using laser-induced fluorescence detection. The test
      was evaluated by using clinical blood specimens from patients with variant (n=5)
      or sporadic (n=4) CJD and patients initially suspected of having CJD who were
      given an alternative diagnosis (n=6). In this context, the ICE assay was
      specific, but incompletely sensitive (55%). The method was unable to detect
      abnormal prion protein in variant CJD brain or spleen reference materials due to
      its loss during the extraction process.

PMID- 16963773
TI  - Titanium dioxide photocatalytic inactivation of prions.
AB  - Prions are postulated to be the infectious agents of a family of transmissible,
      fatal, neurodegenerative disorders affecting both humans and animals. The
      possibility of prion transmission constitutes a public-health risk that confronts
      regulatory authorities everywhere. The main problem in handling prions is the
      fact that they are extremely resistant to standard decontamination methods. Thus,
      the use of harsh and expensive practices to destroy prions is inevitable. The
      development of applicable and efficient prion-inactivation practices is still
      highly important for the prevention of accidental transmission. In the search for
      effective and environmentally friendly methods to eliminate organic compounds and
      bacteria, much attention has been focused on the so-called advanced oxidation
      processes. These are based on the formation of hydroxyl radicals, which are known
      to possess a high reductive potential. This study tested the potential of
      titanium dioxide, an inexpensive and completely inert reagent, to inactivate
      prions in a heterogeneous photocatalytic process. Initial in vitro experiments
      were followed by a bioassay with the scrapie strain 263K in Syrian hamsters. The
      results obtained from this study indicate that titanium dioxide photocatalytic
      treatment of scrapie-infected brain homogenates reduces infectivity titres
      significantly.

PMID- 16963774
TI  - Exportin-5 orthologues are functionally divergent among species.
AB  - Exportin-5, an evolutionarily conserved nuclear export factor belonging to the
      importin-beta family of proteins, is known to play a role in the nuclear export
      of small noncoding RNAs such as precursors of microRNA, viral minihelix RNA and a
      subset of tRNAs in mammalian cells. In this study, we show that the exportin-5
      orthologues from different species such as human, fruit fly and yeast exhibit
      diverged functions. We found that Msn5p, a yeast exportin-5 orthologue, binds
      double-stranded RNAs and that it prefers a shorter 22 nt, double-stranded RNA to
      approximately 80 nt pre-miRNA, even though both of these RNAs share a similar
      terminal structure. Furthermore, we found that Drosophila exportin-5 binds pre
      miRNAs and that amongst the exportin-5 orthologues tested, it shows the highest
      affinity for tRNAs. The knockdown of Drosophila exportin-5 in cultured cells
      decreased the amounts of tRNA as well as miRNA, whereas the knock down of human
      exportin-5 in cultured cells affected only miRNA but not tRNA levels. These
      results indicate that double-stranded RNA binding ability is an inherited
      functional characteristic of the exportin-5 orthologues and that Drosophila
      exportin-5 functions as an exporter of tRNAs as well as pre-miRNAs in the fruit
      fly that lacks the orthologous gene for exportin-t.

PMID- 16963775
TI  - A strand-passage conformation of DNA gyrase is required to allow the bacterial
      toxin, CcdB, to access its binding site.
AB  - DNA gyrase is the only topoisomerase able to introduce negative supercoils into
      DNA. Absent in humans, gyrase is a successful target for antibacterial drugs.
      However, increasing drug resistance is a serious problem and new agents are
      urgently needed. The naturally-produced Escherichia coli toxin CcdB has been
      shown to target gyrase by what is predicted to be a novel mechanism. CcdB has
      been previously shown to stabilize the gyrase 'cleavage complex', but it has not
      been shown to inhibit the catalytic reactions of gyrase. We present data showing
      that CcdB does indeed inhibit the catalytic reactions of gyrase by stabilization
      of the cleavage complex and that the GyrA C-terminal DNA-wrapping domain and the
      GyrB N-terminal ATPase domain are dispensable for CcdB's action. We further
      investigate the role of specific GyrA residues in the action of CcdB by site
      directed mutagenesis; these data corroborate a model for CcdB action based on a
      recent crystal structure of a CcdB-GyrA fragment complex. From this work, we are
      now able to present a model for CcdB action that explains all previous
      observations relating to CcdB-gyrase interaction. CcdB action requires a
      conformation of gyrase that is only revealed when DNA strand passage is taking
      place.

PMID- 16963776
TI  - Dynamic assembly of primers on nucleic acid templates.
AB  - A strategy is presented that uses dynamic equlibria to assemble in situ composite
      DNA polymerase primers, having lengths of 14 or 16 nt, from DNA fragments that
      are 6 or 8 nt in length. In this implementation, the fragments are transiently
      joined under conditions of dynamic equilibrium by an imine linker, which has a
      dissociation constant of approximately 1 muM. If a polymerase is able to extend
      the composite, but not the fragments, it is possible to prime the synthesis of a
      target DNA molecule under conditions where two useful specificities are combined:
      (i) single nucleotide discrimination that is characteristic of short
      oligonucleotide duplexes (four to six nucleobase pairs in length), which
      effectively excludes single mismatches, and (ii) an overall specificity of
      priming that is characteristic of long (14 to 16mers) oligonucleotides,
      potentially unique within a genome. We report here the screening of a series of
      polymerases that combine an ability not to accept short primer fragments with an
      ability to accept the long composite primer held together by an unnatural imine
      linkage. Several polymerases were found that achieve this combination, permitting
      the implementation of the dynamic combinatorial chemical strategy.

PMID- 16963778
TI  - Twin gradients in APOBEC3 edited HIV-1 DNA reflect the dynamics of lentiviral
      replication.
AB  - The human immunodeficiency virus (HIV) Vif protein blocks incorporation of two
      host cell cytidine deaminases, APOBEC3F and 3G, into the budding virion. Not
      surprisingly, on a vif background nascent minus strand DNA can be extensively
      edited leaving multiple uracil residues. Editing occurs preferentially in the
      context of TC (GA on the plus strand) and CC (GG) depending on the enzyme. To
      explore the distribution of APOBEC3F and -3G editing across the genome, a
      product/substrate ratio (AA + AG)/(GA + GG) was computed for a series of 30
      edited genomes present in the data bases. Two highly polarized gradients were
      noted each with maxima just 5' to the central polypurine tract (cPPT) and LTR
      proximal polypurine tract (3'PPT). The gradients are in remarkable agreement with
      the time the minus strand DNA remains single stranded. In vitro analyses of
      APOBEC3G deamination of nascent cDNA spanning the two PPTs showed no pronounced
      dependence on the PPT RNA:DNA heteroduplex ruling out the competing hypothesis of
      a PPT orientation effect. The degree of hypermutation varied smoothly among
      genomes indicating that the number of APOBEC3 molecules packaged varied
      considerably.

PMID- 16963777
TI  - Organization of chromosome ends in the rice blast fungus, Magnaporthe oryzae.
AB  - Eukaryotic pathogens of humans often evade the immune system by switching the
      expression of surface proteins encoded by subtelomeric gene families. To
      determine if plant pathogenic fungi use a similar mechanism to avoid host
      defenses, we sequenced the 14 chromosome ends of the rice blast pathogen,
      Magnaporthe oryzae. One telomere is directly joined to ribosomal RNA-encoding
      genes, at the end of the approximately 2 Mb rDNA array. Two are attached to
      chromosome-unique sequences, and the remainder adjoin a distinct subtelomere
      region, consisting of a telomere-linked RecQ-helicase (TLH) gene flanked by
      several blocks of tandem repeats. Unlike other microbes, M.oryzae exhibits very
      little gene amplification in the subtelomere regions-out of 261 predicted genes
      found within 100 kb of the telomeres, only four were present at more than one
      chromosome end. Therefore, it seems unlikely that M.oryzae uses switching
      mechanisms to evade host defenses. Instead, the M.oryzae telomeres have undergone
      frequent terminal truncation, and there is evidence of extensive ectopic
      recombination among transposons in these regions. We propose that the M.oryzae
      chromosome termini play more subtle roles in host adaptation by promoting the
      loss of terminally-positioned genes that tend to trigger host defenses.

PMID- 16963779
TI  - Association of nucleoid proteins with coding and non-coding segments of the
      Escherichia coli genome.
AB  - The Escherichia coli chromosome is condensed into an ill-defined structure known
      as the nucleoid. Nucleoid-associated DNA-binding proteins are involved in
      maintaining this structure and in mediating chromosome compaction. We have
      exploited chromatin immunoprecipitation and high-density microarrays to study the
      binding of three such proteins, FIS, H-NS and IHF, across the E.coli genome in
      vivo. Our results show that the distribution of these proteins is biased to
      intergenic parts of the genome, and that the binding profiles overlap. Hence some
      targets are associated with combinations of bound FIS, H-NS and IHF. In addition,
      many regions associated with FIS and H-NS are also associated with RNA
      polymerase.

PMID- 16963780
TI  - The proteomics of N-terminal methionine cleavage.
AB  - Methionine aminopeptidase (MAP) is a ubiquitous, essential enzyme involved in
      protein N-terminal methionine excision. According to the generally accepted
      cleavage rules for MAP, this enzyme cleaves all proteins with small side chains
      on the residue in the second position (P1'), but many exceptions are known. The
      substrate specificity of Escherichia coli MAP1 was studied in vitro with a large
      (>120) coherent array of peptides mimicking the natural substrates and
      kinetically analyzed in detail. Peptides with Val or Thr at P1' were much less
      efficiently cleaved than those with Ala, Cys, Gly, Pro, or Ser in this position.
      Certain residues at P2', P3', and P4' strongly slowed the reaction, and some
      proteins with Val and Thr at P1' could not undergo Met cleavage. These in vitro
      data were fully consistent with data for 862 E. coli proteins with known N
      terminal sequences in vivo. The specificity sites were found to be identical to
      those for the other type of MAPs, MAP2s, and a dedicated prediction tool for Met
      cleavage is now available. Taking into account the rules of MAP cleavage and
      leader peptide removal, the N termini of all proteins were predicted from the
      annotated genome and compared with data obtained in vivo. This analysis showed
      that proteins displaying N-Met cleavage are overrepresented in vivo. We conclude
      that protein secretion involving leader peptide cleavage is more frequent than
      generally thought.

PMID- 16963781
TI  - PTEN regulates fibroblast elimination during collagen matrix contraction.
AB  - During tissue repair, excess fibroblasts are eliminated by apoptosis. This
      physiologic process limits fibrosis and restores normal anatomic patterns.
      Replicating physiologic apoptosis associated with tissue repair, fibroblasts
      incorporated into type I collagen matrices undergo apoptosis in response to
      collagen matrix contraction. In this in vitro model of wound repair, fibroblasts
      first attach to collagen via alpha2beta1 integrin. This provides a survival
      signal via activation of the phosphatidylinositol 3-kinase/Akt signal pathway.
      However, during subsequent collagen matrix contraction, the level of
      phosphorylated Akt progressively declines, triggering apoptosis. The mechanism
      underlying the fall in phosphorylated Akt is incompletely understood. Here we
      show that PTEN phosphatase becomes activated during collagen matrix contraction
      and is responsible for antagonizing phosphatidylinositol 3-kinase activity and
      promoting a decline in phosphorylated Akt and fibroblast apoptosis in response to
      collagen contraction. PTEN null fibroblasts displayed enhanced levels of
      phosphorylated Akt and were resistant to collagen matrix contraction-induced
      apoptosis. Reconstitution of PTEN in PTEN null cells conferred susceptibility to
      apoptosis in response to contraction of collagen matrices. Consistent with this,
      knockdown of PTEN in PTEN(+/+) embryonic fibroblasts by small interfering RNA
      augmented Akt activity and suppressed apoptosis in contractile collagen matrices.
      Furthermore, inhibition of Akt activity restored the sensitivity of PTEN null
      cells to collagen contraction-induced apoptosis, indicating that the mechanism by
      which PTEN alters fibroblast viability is through modulation of phosphorylated
      Akt levels. Our work suggests that collagen matrix contraction activates PTEN by
      a mechanism involving cytoskeletal disassembly. Our studies indicate a key role
      for PTEN in regulating fibroblast viability during tissue repair.

PMID- 16963783
TI  - Implementation of an online tailored physical activity intervention for adults in
      Belgium.
AB  - It has been argued that the Internet is a promising channel for distribution of
      health promoting programs, because of its advantage to reach a wide variety of
      people at once, at any time and location. However, little research is done to
      study how we could prompt people to use these online health promoting programs.
      Therefore the main objective of the present study was to assess if a face-to-face
      contact stimulates adults to visit a recently developed tailored physical
      activity website to promote more physical activity in the general Belgian
      population. The second objective was to test the website under real-life
      conditions in a small sample. Therefore, 200 flyers, with a call for evaluating
      the new tailored physical activity website, were distributed to hospital visitors
      in two different ways. One group of visitors were personally approached by a
      research assistant and handed over a flyer. Another 100 visitors could simply
      take a flyer home, without initial personal contact. After two months, telephone
      interviews were done to make a qualitative evaluation of the website. The results
      showed that obviously more participants with an initial face-to-face contact
      (46%) registered on the website in comparison with the participants without
      personal contact (6%). The used strategy reaches participants of both sexes as
      well as regular and irregular Internet users. Secondly, the telephone interviews
      indicated that the website was accepted well, without major problems. We could
      conclude that distributing flyers combined with a short face-to-face contact,
      increased the number of visitors compared with distributed flyers without contact
      and that the tailored physical activity website could be used in real-life
      situations to promote an active lifestyle in Belgium. However, a controlled study
      with a larger sample size should be done to test the effectiveness of the
      tailored intervention in increasing physical activity.

PMID- 16963782
TI  - Self-association of collagen triple helic peptides into higher order structures.
AB  - Interest in self-association of peptides and proteins is motivated by an interest
      in the mechanism of physiologically higher order assembly of proteins such as
      collagen as well as the mechanism of pathological aggregation such as beta
      amyloid formation. The triple helical form of (Pro-Hyp-Gly)(10), a peptide that
      has proved a useful model for molecular features of collagen, was found to self
      associate, and its association properties are reported here. Turbidity
      experiments indicate that the triple helical peptide self-assembles at neutral pH
      via a nucleation-growth mechanism, with a critical concentration near 1 mM. The
      associated form is more stable than individual molecules by about 25 degrees C,
      and the association is reversible. The rate of self-association increases with
      temperature, supporting an entropically favored process. After self-association,
      (Pro-Hyp-Gly)(10) forms branched filamentous structures, in contrast with the
      highly ordered axially periodic structure of collagen fibrils. Yet a number of
      characteristics of triple helix assembly for the peptide resemble those of
      collagen fibril formation. These include promotion of fibril formation by neutral
      pH and increasing temperature; inhibition by sugars; and a requirement for
      hydroxyproline. It is suggested that these similar features for peptide and
      collagen self-association are based on common lateral underlying interactions
      between triple helical molecules mediated by hydrogen-bonded hydration networks
      involving hydroxyproline.

PMID- 16963784
TI  - A controlled trial of a school-based environmental intervention to improve
      physical activity in Dutch children: JUMP-in, kids in motion.
AB  - Interventions to promote physical activity are important in preventing children
      from becoming overweight. Many projects have been developed but only a few showed
      (moderate) effects. JUMP-in is a systematically developed primary-school-based
      intervention that focuses on the use of theory, environmental changes, parental
      influences and cooperation with multi-level parties in intervention development.
      The effects of JUMP-in were evaluated with a quasi-experimental pre-test/post
      test research design. In total, 510 children from Grades 4, 5 and 6 of four
      intervention schools and two control schools in Amsterdam were followed for an
      intervention period of one school year. Changes in physical activity as well as
      in the social cognitive determinants were assessed using self-reports. In
      addition, a process evaluation has been executed. The results show that JUMP-in
      was effective in influencing physical activity, especially among children from
      Grade 6. Children in the control group decreased their level of physical activity
      considerably, while activity levels in intervention children from Grade 6
      remained stable. The intervention effects could not be explained by changes in
      the measured social cognitive determinants. In contrast, process information
      illuminated differences in intervention effects between the participating
      schools. The results from the JUMP-in study show the importance of intervention
      designs that focus on a theory-based mix of relevant environmental and social
      cognitive factors.

PMID- 16963785
TI  - The results of a worksite health promotion programme in Kuala Lumpur, Malaysia.
AB  - The worksite is one of the key channels for the delivery of interventions to
      reduce chronic diseases among adult populations. It provides easy and regular
      access to a relatively stable population and it encourages sustained peer
      support. This paper reports a 2-year follow-up of the impact of a worksite health
      promotion programme on serum cholesterol and dietary changes among employees in a
      city in Malaysia. A quasi-experimental study was conducted among Malay-Muslim
      male security guards, with those working in a public university in Kuala Lumpur
      comprising the intervention group, and those working in the teaching hospital of
      the same university as the comparison group. They were comparable in socio
      demographic characteristics. The intervention group received intensive individual
      and group counselling on diet, physical activity and quitting smoking. The
      comparison group was given minimal education on the same lifestyle changes
      through mail and group counselling. The intervention group showed a statistically
      significant reduction in their mean total cholesterol levels as compared with the
      comparison group, with an intervention effect of -0.38 (95% CI = -0.63, -0.14)
      mmol/l. The intervention group also reported a reduction in the amount of
      cigarettes smoked. The worksite was shown to be an effective channel for health
      promotion. The adoption of the new lifestyle behaviours should be supported and
      sustained through modification of work policies.

PMID- 16963786
TI  - Probing dynamics and conformational change of the GroEL-GroES complex by 13C NMR
      spectroscopy.
AB  - Bacterial chaperonin GroEL with a molecular mass of 800 kDa was studied by (13)C
      NMR spectroscopy. Carbonyl carbons of GroEL were labeled with (13)C in an amino
      acid specific manner in order to reduce the number of signals to be observed in
      the spectrum. Combination of selective labeling and site-directed mutagenesis
      enabled us to establish the sequence specific assignment of the (13)C resonances
      from GroEL. ADP-binding induced a chemical shift change of Tyr478 in the
      equatorial domain and His401 in the intermediate domain, but little of Tyr203 in
      the apical domain. Upon complex formation with co-chaperonin GroES in the
      presence of ADP, Tyr478 exhibits two peaks that would originate from the cis and
      trans rings of the asymmetric GroEL-GroES complex. Comparison between the line
      width of the GroEL resonances and those from GroES in complex with GroEL revealed
      broadening disproportionate to the size of GroEL, implying the existence of
      conformational fluctuations which may be pertinent to the chaperone activity.
      Based on these results, we concluded that (13)C NMR observation in combination
      with selective labeling and site-directed mutagenesis can be utilized for probing
      the conformational change and dynamics of the extremely large molecules that are
      inaccessible with current NMR methods.

PMID- 16963787
TI  - Active-site properties of Phrixotrix railroad worm green and red bioluminescence
      eliciting luciferases.
AB  - The luciferases of the railroad worm Phrixotrix (Coleoptera: Phengodidae) are the
      only beetle luciferases that naturally produce true red bioluminescence.
      Previously, we cloned the green- (PxGR) and red-emitting (PxRE) luciferases of
      railroad worms Phrixotrix viviani and P. hirtus[OLE1]. These luciferases were
      expressed and purified, and their active-site properties were determined. The red
      emitting PxRE luciferase displays flash-like kinetics, whereas PxGR luciferase
      displays slow-type kinetics. The substrate affinities and catalytic efficiency of
      PxRE luciferase are also higher than those of PxGR luciferase. Fluorescence
      studies with 8-anilino-1-naphthalene sulfonic acid and 6-p-toluidino-2
      naphthalene sulfonic acid showed that the PxRE luciferase luciferin-binding site
      is more polar than that of PxGR luciferase, and it is sensitive to guanidine.
      Mutagenesis and modelling studies suggest that several invariant residues in the
      putative luciferin-binding site of PxRE luciferase cannot interact with excited
      oxyluciferin. These results suggest that one portion of the luciferin-binding
      site of the red-emitting luciferase is tighter than that of PxGR luciferase,
      whereas the other portion could be more open and polar.

PMID- 16963788
TI  - Characterization of heme-coordinating histidyl residues of cytochrome b5 based on
      the reactivity with diethylpyrocarbonate: a mechanism for the opening of axial
      imidazole rings.
AB  - We investigated the reactivity of heme-coordinating imidazole with
      diethylpyrocarbonate using a soluble domain of cytochrome b(5). Analyses with
      various spectroscopic methods including MALDI-TOF-MS indicated that two axial His
      residues (His44 and His68) of cytochrome b(5) were protected from the
      modification by several factors, i.e., limited steric exposure of the axial
      imidazole to the solvent, the Fe-N(epsilon2) coordination bond, and protonation
      of the N(delta1) position by forming a hydrogen bond with its immediate
      surroundings. However, once N-carbethoxylation at the N(epsilon2) position of the
      axial His residues occurred with a higher concentration of diethylpyrocarbonate,
      displacement of heme prosthetic group from the protein moiety continued.
      Simultaneously, it facilitated the second N-carbethoxylation to take place at the
      N(epsilon1) position of the same imidazole ring, leading to a bis-N
      carbethoxylated derivative and further to a ring-opened derivative. A similar
      mechanism seemed in operation for one non-axial His residue (His85), in which the
      N(delta1) atom works as a hydrogen acceptor in a strong hydrogen-bond and the
      other N(epsilon2) atom is in a protonated form, resulting in a formation of the
      ring-opened derivative upon treatment with a higher concentration of
      diethylpyrocarbonate. These results suggested that the use of
      diethylpyrocarbonate for MALDI-TOF-MS analysis might provide a unique method to
      characterize the protonation state of His residues and the strength of their
      hydrogen-bondings at the active site of enzymes.

PMID- 16963789
TI  - Inspired oxygen fraction of 0.8 compared with 0.4 does not further reduce
      postoperative nausea and vomiting in dolasetron-treated patients undergoing
      laparoscopic cholecystectomy.
AB  - BACKGROUND: Postoperative nausea and vomiting (PONV) is one of the most frequent
      complications after general anaesthesia. Single-dose antiemetic prophylaxis has
      limited efficacy in high-risk patients. Adding a simple potential antiemetic
      approach, such as increasing the inspired oxygen fraction, to the antiemetic
      portfolio would preserve pharmacological interventions for treatment of symptoms
      in the postoperative period. However, the antiemetic effect of a high inspired
      oxygen fraction is still discussed controversially. The aim of the study was to
      evaluate whether an inspired oxygen fraction of 0.8 decreases PONV in patients
      receiving the 5-HT3-antagonist dolasetron. METHODS: In a randomized, placebo
      controlled, double-blinded trial we studied 377 patients (ASA I-III) undergoing
      elective laparoscopic cholecystectomy. Induction of anaesthesia was standardized,
      including thiopental fentanyl and cis-atracurium. For all patients the individual
      risk for PONV was calculated using the Koivuranta score and all patients received
      12.5 mg dolasetron i.v. before surgery. Patients were allocated randomly to one
      of three groups: Group A (n=125) received 80% oxygen in air, Group B (n=125) 40%
      oxygen in air and Group C (n=127) 40% oxygen in nitrous oxide. Postoperative
      nausea, postoperative vomiting (PV), or nausea, vomiting, or both (PONV) was
      assessed in the early (0-4 h) and overall postoperative period (0-24 h) by an
      anaesthesiologist unaware of patient allocation. RESULTS: There was a
      significantly lower incidence of PONV and PV in Groups A (PONV: 11.2%; PV: 3.2%)
      and B (PONV: 10.4%; PV: 3.2%) compared with Group C (PONV: 26.7%; PV: 13.3%), but
      there were no significant differences between Groups A and B. CONCLUSIONS: An
      inspired oxygen fraction of 0.8 does not further decrease PONV or vomiting in
      dolasetron-treated patients undergoing laparoscopic cholecystectomy. The lower
      incidence of PONV in Groups A and B compared with Group C is most likely caused
      by the omission of nitrous oxide.

PMID- 16963790
TI  - Economics and public health: engaged to be happily married!

PMID- 16963791
TI  - Integrin ligands mobilize Ca2+ from ryanodine receptor-gated stores and lysosome
      related acidic organelles in pulmonary arterial smooth muscle cells.
AB  - Extracellular matrix (ECM) protein receptors, or integrins, participate in
      vascular remodeling and the systemic myogenic response. Synthetic ligands and ECM
      fragments regulate the vascular smooth muscle cell contractile state by altering
      intracellular Ca2+ levels ([Ca2+]i). Information on the Ca2+ effect of integrins
      in vascular smooth muscle cells is limited, but nonexistent in pulmonary arterial
      smooth muscle cells (PASMCs). We therefore characterized integrin expression in
      endothelium-denuded pulmonary arteries, and explored [Ca2+]i mobilization
      pathways induced by soluble ligands in rat PASMCs. Reverse transcriptase-PCR
      showed mRNA expression of integrins alpha1, alpha2, alpha3, alpha4, alpha5,
      alpha7, alpha8, alpha(v), beta1, beta3, and beta4, and immunoblots of alpha5,
      alpha(v), beta1, and beta3 confirmed protein expression. Exposure of PASMCs to
      integrin-binding peptides (0.5 mM) containing the arginine-glycine-aspartate
      (RGD) motif elicited [Ca2+]i responses with an order of potency of GRGDNP >
      GRGDSP > GRGDTP = cyclo-RGD. Pharmacological analysis revealed that the GRGDSP
      induced Ca2+ response was unrelated to Ca2+ influx and the inositol triphosphate
      receptor-gated Ca2+ store, but partially blocked by ryanodine or inhibition of
      lysosome-related acidic organelles with bafilomycin A1. Simultaneous inhibition
      of both pathways was necessary to abolish the response. GRGDSP treatment
      increased cyclic ADP-ribose, the endogenous activator of ryanodine receptors, by
      70%. GRGDSP also rapidly reduced Lysotracker Red accumulation, confirming direct
      modulation of acidic organelles. These data are the first demonstration of
      integrin-mediated Ca2+ regulation in PASMCs. The presence of an array of
      integrins, and activation of ryanodine-sensitive Ca2+ stores and lysosome-like
      organelles by GRGDSP suggest important roles for integrin-dependent Ca2+
      signaling in regulating PASMC function.

PMID- 16963792
TI  - Introduction to in vitro estimation of metabolic stability and drug interactions
      of new chemical entities in drug discovery and development.
AB  - Determination of metabolic properties of a new chemical entity (NCE) is one of
      the most important steps during the drug discovery and development process.
      Nowadays, in vitro methods are used for early estimation and prediction of in
      vivo metabolism of NCEs. Using in vitro methods, it is possible to determine the
      metabolic stability of NCEs as well as the risk for drug-drug interactions (DDIs)
      related to inhibition and induction of drug metabolic enzymes. Metabolic
      stability is defined as the susceptibility of a chemical compound to
      biotransformation, and is expressed as in vitro half-life (t(1/2)) and intrinsic
      clearance (CL(int)). Based on these values, in vivo pharmacokinetic parameters
      such as bioavailability and in vivo half-life can be calculated. The drug
      metabolic enzymes possess broad substrate specificity and can metabolize multiple
      compounds. Therefore, the risk for metabolism-based DDIs is always a potential
      problem during the drug development process. For this reason, inhibition and
      induction in vitro screens are used early, before selection of a candidate drug
      (CD), to estimate the risk for clinically significant DDIs. At present, most
      pharmaceutical companies perform in vitro drug metabolism studies together with
      in silico prediction software and automated high-throughput screens (HTS).
      Available data suggest that in vitro methods are useful tools for identification
      and elimination of NCEs with unappreciated metabolic properties. However, the
      quantitative output of the methods has to be improved. The aim of this review is
      to highlight the practical and theoretical basis of the in vitro metabolic
      methods and the recent progress in the development of these assays.

PMID- 16963793
TI  - Methotrexate in rheumatoid arthritis.
AB  - A variety of disease-modifying antirheumatic drugs (DMARDs) are available to
      control the clinical activity of rheumatoid arthritis (RA). Methotrexate (MTX),
      an analogue of folic acid and of aminopterin, is the most commonly used DMARD and
      is now prescribed worldwide to at least 500,000 patients with RA. The mechanism
      by which MTX used at a low dose modulates inflammation in RA is still unknown.
      Monitoring of the therapy in terms of MTX concentration in patients with RA seems
      not to have a significant influence on the effectiveness of the treatment. Two
      meta-analyses showed that MTX has one of the best efficacy/toxicity ratios. It
      should be the first DMARD used in the majority of patients with RA at this time.
      However, a significant number of patients treated only with MTX fail to achieve
      optimal disease control, so there are many combinations of DMARD regimes. It is
      hoped that more aggressive use of conventional DMARDs and biological agents will
      result in less disability and a higher proportion of patients achieving
      remission. The therapy of RA is a dynamic process and requires maintaining a
      delicate balance between benefits and risks. Even with the newer biological
      agents, MTX continues to serve as a reference point and there is still a role for
      MTX in the treatment of RA patients.

PMID- 16963794
TI  - Mechanism of synergistic action following co-treatment with pramipexole and
      fluoxetine or sertraline in the forced swimming test in rats.
AB  - The aim of the present study was to examine the effect of combined treatment of
      male Wistar rats with pramipexole and fluoxetine or sertraline in the forced
      swimming test. The obtained results showed that co-treatment with pramipexole
      (0.1 mg/kg) and fluoxetine (10 mg/kg) or sertraline (5 mg/kg) (in doses inactive
      per se) exhibited antidepressant-like activity in the forced swimming test.
      Sulpiride (a dopamine D(2/3) receptor antagonist) and WAY 100635 (a 5-HT(1A)
      receptor antagonist), either being ineffective in the forced swimming test,
      inhibited the antidepressant-like effect induced by co-administration of
      pramipexole and fluoxetine or sertraline. However, SCH 23390 (a dopamine D(1)
      receptor antagonist) only partly did not alter the effect of pramipexole given
      jointly with antidepressant drugs; on the other hand, S 33084 (a dopamine D(3)
      receptor antagonist) only partly decreased (in a statistically insignificant
      manner) that effect. Moreover, progesterone and BD 1047 (a sigma(1) receptor
      antagonist) counteracted the antidepressant-like effect induced by co
      administration of pramipexole and sertraline (but not pramipexole and
      fluoxetine). In that test, active behavior did not reflect the increases in
      general activity, since combined administration of pramipexole and fluoxetine or
      sertraline failed to enhance the locomotor activity of rats. None of the tested
      drugs (SCH 23390, sulpiride, S 33084, WAY 100635, BD 1047 and progesterone) -
      alone or in combination with pramipexole and fluoxetine or sertraline - changed
      locomotor activity. The results described in the present paper indicate that co
      administration of pramipexole and fluoxetine or sertraline may induce a more
      pronounced antidepressive activity than does treatment with pramipexole alone,
      and that in addition to other mechanisms, dopamine D(2/3) and 5-HT(1A) receptors
      may contribute to the antidepressant-like activity of pramipexole and fluoxetine
      or sertraline in the forced swimming test in rats. Moreover, sigma(1) receptors
      may constitute one of the possible mechanisms by which co-administration of
      pramipexole and sertraline induces antidepressant-like activity in that test.

PMID- 16963796
TI  - Serum kynurenic acid positively correlates with cardiovascular disease risk
      factor, homocysteine: a study in stroke patients.
AB  - KYNA, an antagonist of ionotropic glutamate receptors and alpha7 nicotinic
      receptors, has been found as well in the brain as in the periphery. The altered
      metabolism of KYNA, especially its deficiency, can lead to the enhanced glutamate
      mediated excitotoxicity, and was suggested to be a factor contributing to the
      development of neurodegeneration and seizures. Elevated serum concentration of
      homocysteine is considered to be an independent risk factor of atherosclerosis
      and is an emerging risk factor of cognitive dysfunction and stroke. In the
      present study, serum level of KYNA, homocysteine and other biochemical parameters
      were assessed in patients at early (up to 24 h after infarct) stage of stroke.
      Serum KYNA and homocysteine levels were similar in control (N = 26) and stroke (N
      = 24) groups. KYNA level correlated positively with the level of homocysteine in
      control and in stroke group, with p = 0.018; r = 0.462 and p = 0.027; r = 0.451,
      respectively. In control group, KYNA correlated positively also with age (p =
      0.007; r = 0.514) and with creatinine level (p = 0.002; r = 0.581). In stroke
      group, serum KYNA correlated positively with creatinine (p = 0.001; r = 0.644)
      and with urea level (p < 0.001; r = 0.716). Homocysteine level correlated
      inversely with folate level in control (p = 0.01; r = -0.499) but not in stroke
      group (p = 0.13; r = -0.317). Serum homocysteine in stroke group correlated
      positively also with age (p = 0.001; r = 0.6401), and with urea level (p = 0.017;
      r = 0.4813). Clinical significance of the association between serum KYNA and
      homocysteine levels requires further investigation.

PMID- 16963795
TI  - Therapeutic tricyclic antidepressant drug monitoring in younger and older
      depressive patients.
AB  - The present study shows the evaluation of clinical state and serum level of
      tricyclic antidepressants in thirty-eight depressive younger and elderly patients
      during 8-week observation. We observed no statistically significant differences,
      neither in psychometric scale scores nor in drug serum levels in both groups of
      patients.

PMID- 16963797
TI  - Apoptotic markers in various stages of amygdala kindled seizures in rats.
AB  - The aim of the study was to elucidate the relationship between various stages of
      amygdala kindling in rats and neuronal apoptosis. We used the unbiased method of
      RNase protection assay (RPA), measuring expression of several apoptosis
      associated genes (for: caspase 1, caspase 2, caspase 3, FAS antigen, bax and bcl
      x, bcl-2). The obtained results were also verified in situ in hippocampal slices,
      using the TUNEL method. The mRNA level of the investigated genes was estimated by
      densitometry and standardized according to the amount of L32 RNA. Only the
      expression of bcl-x L, caspase 2, caspase 3 and bax genes was measureable. In all
      experimental groups, the mRNA levels of bax and bcl-x genes were higher than mRNA
      of caspase-2 and caspase-3 genes. However, there were no statistically
      significant differences between the control and kindled animals. On the other
      hand, the TUNEL positive cells were found in total contralateral hippocampus of
      investigated animals belonging to C(0) (control group), C(3) (rats with 3rd stage
      of seizures) and c(5) (rats with 5th stage of seizures) groups. The number of
      TUNEL positive cells in the hippocampus was significantly higher in C(3) and C(5)
      groups (4.0 +/- 0.40 and 3.75 +/- 0.49) when compared to C(0) group (1.25 +/-
      0.25). In conclusion, although apoptotic cells were found in situ in the
      hippocampus of kindled rats, RNase protection assay failed to measure any changes
      in mRNA levels of the chosen apoptotic genes. In our opinion, apoptotic cells
      might be too rare to detect any changes in gene expression. Therefore, the TUNEL
      procedure still remains the most favorable method of apoptotic cell death
      evaluation in the brain structures.

PMID- 16963798
TI  - Efficacy of bretazenil against cortical epileptic afterdischarges increases
      during early ontogeny in rats.
AB  - The effect of a benzodiazepine partial agonist bretazenil on cortical epileptic
      afterdischarges was studied in 12-, 18- or 25-day-old rat pups with implanted
      electrodes. Afterdischarges were induced by low-frequency stimulation of
      sensorimotor area four times in each animal and bretazenil (0.1; 1; 5; 10; or 25
      mg/kg) and/or solvent were administered intraperitoneally between the first and
      second stimulation. Bretazenil was able to decrease the duration of
      afterdischarges as well as intensity of clonic seizures accompanying these
      afterdischarges in all age groups in a dose-dependent manner. The efficacy of
      bretazenil was age-dependent: the most marked effect on duration of
      afterdischarges was observed in 25-day-old rats. It is in sharp contrast with our
      earlier data for full agonists clonazepam and midazolam demonstrating the
      strongest action in the youngest group.

PMID- 16963799
TI  - Comparative study of multiple dosage of quercetin against cisplatin-induced
      nephrotoxicity and oxidative stress in rat kidneys.
AB  - Quercetin, a typical bioflavonoid ubiquitously present in fruits and vegetables,
      is considered to be helpful for human health. Cisplatin (cDDP) is one of the most
      active cytotoxic agents in the treatment of a wide range of solid tumors. The aim
      of this study was to investigate the possible effect of quercetin, a bioflavonoid
      with antioxidant potential, on cisplatin-induced nephrotoxicity and lipid
      peroxidation in rats. Gavage administrations of water, propylene glycol and
      quercetin (50 mg/kg) were made 24 and 1 h before saline or cDDP (5 mg/kg) ip
      injections and were repeated daily for 2, 5 or 20 subsequent days. Rats were
      killed 2, 5 and 20 days after ip injections, and blood and urine samples were
      collected to determine plasma creatinine, urine volume and osmolality. The
      kidneys were removed to determine the levels of thiobarbituric acid-reactive
      substances (TBARS) and for histological studies. Cisplatin increased lipid
      peroxidation, urine volume and plasma creatinine levels and decreased urine
      osmolality. Treatment with quercetin attenuated these alterations. These results
      demonstrate the role of oxidative stress and suggest a protective effect of
      quercetin on cisplatin-induced nephrotoxicity in adult Wistar rats.

PMID- 16963800
TI  - Pharmacological activity of calcimimetic NPS R-568 administered intravenously in
      rats: dose dependency.
AB  - Calcimimetics administered orally cause "pharmacological parathyroidectomy"
      confirmed by a decrease in parathyroid hormone secretion (PTH) and in plasma
      Ca(2+) concentration. Parathyroids are also the source of parathyroid
      hypertensive factor (PHF). The aim of this study was to determine the dose
      dependent effect of an intravenously (iv) applied calcimimetic, NPS R-568, on
      plasma Ca(2+) concentration, urinary phosphate excretion and mean arterial blood
      pressure (MAP) in rats. Clearance experiments were performed on male Wistar rats
      anesthetized with thiopental and infused iv with saline supplemented with (3)H
      inulin for glomerular filtration rate (GFR) determination. NPS R-568 was
      administered iv as a bolus at the doses: 0.5, 1.0, 2.5 and 5.0 mg/kg. Control
      group of rats received vehicle only. MAP was monitored continuously in the
      carotid artery. Urine was collected from cannulated urinary bladder. NPS R-568
      applied iv dose-dependently decreased plasma Ca(2+) and fractional phosphate
      excretion (FE(Pi)). In the control group, no significant changes in plasma Ca(2+)
      and FE(Pi) were observed. The most efficient hypotensive effect vs. control group
      was induced by the NPS R-568 of a dose of 1.0 mg/kg. Our results indicate that
      the dose of 1 mg/kg of the calcimimetic NPS R-568 administered iv is sufficient
      to induce the decrease in plasma Ca(2+) and urinary phosphate excretion
      accompanied with hypotensive effect in Wistar rats.

PMID- 16963801
TI  - Effects of catecholamines on the intramedullary pressure in the femur in rats
      with prednisolone-induced osteoporosis.
AB  - Osteoporosis is a metabolic bone disease characterized by low bone mass, impaired
      micro-architecture and susceptibility to fracture. Osteoporosis may be, inter
      alia, a result of a long-term glucocorticosteroid therapy, e.g. with
      prednisolone. Although a number of properties of prednisolone in influencing bone
      metabolism have been recognized, the effect of prednisolone-induced osteoporosis
      on the function of blood circulation and autonomic nervous system in bones
      remains open. In order to clarify this problem, the present study concentrated on
      the effects of catecholamines on intramedullary pressure in rats with
      prednisolone-induced osteoporosis. Prednisolone was administered to male Wistar
      rats at the doses of 5 mg/kg im, for 3 weeks. Norepinephrine, epinephrine,
      isoprenaline as well as adrenoceptor antagonists (phentolamine and propranolol)
      were administered to the controls and to the rats with prednisolone-induced
      osteoporosis. The examinations demonstrated that rats with prednisolone-induced
      osteoporosis displayed a decreased intramedullary pressure. In addition, a
      disordered effect of catecholamines on intramedullary pressure of osteoporotic
      bone was observed.

PMID- 16963802
TI  - Study of the interaction of 1,4-dihydropyridine derivatives with glucocorticoid
      hormone receptors from the rat liver.
AB  - Seventeen derivatives of 1,4-dihydropyridine (DHP) series were tested in vitro
      for their ability to inhibit [1,2,4-(3)H]-dexamethasone binding to glucocorticoid
      receptor from the rat liver cytosol. Depending on structural features and
      inhibiting activities, the compounds can be divided into three groups. The first
      group (nifedipine, foridone, J-6-163, OSI-4164 and OSI-7724) had the highest
      activity: they inhibited specific ligand-receptor binding by 70-80% at
      concentrations of 10(-5) M and 10(-4) M, with apparent IC(50)values of 1.5-6.0
      muM. The second group (cerebrocrast, diethone, OSI-1211 and OSI-7265) was active
      at concentration of 10(-4) M, and their IC(50) values were 23-45 muM; compound
      OSI-5003 was almost inactive. Both groups are compounds with scarce water
      solubility, more or less lipophilic. The third group of compounds comprises
      ionogenic compounds (organic cations or anions with corresponding inorganic
      counterions): most of them are water-soluble (glutapyrone, carbatone,
      gammapyrone, OSI-2780, OSI-1580, OSI-2140) or liposome-forming (A-74). They lack
      the above-mentioned activity. Among the first two groups, compounds possessing
      more bulky substituents in positions 3 and 5 are less active. The aromatic ring
      in the position 4 is essential for the optimal activity. It seems that there is a
      bell-shaped dependence of activity upon lipophilicity. In general, the compounds
      of the first group are strong Ca-antagonists, while the second group includes
      moderate Ca-antagonists, but each group comprises also compounds which lack Ca
      antagonistic activity. All compounds of the third group lack Ca antagonistic
      properties.

PMID- 16963803
TI  - Trimetazidine increases [3H]glucose uptake in rat brain.
AB  - Trimetazidine, a clinically effective antianginal agent with no negative
      inotropic or vascular properties, acts by optimizing cardiac energy metabolism
      through inhibition of free fatty acid oxidation, shifting substrate utilization
      from fatty acids to glucose. Up to now there has been no study associating
      trimetazidine's effect on metabolic processes with glucose utilization in the
      mammalian brain. The objective of the present study was to determine if
      trimetazidine altered [(3)H]glucose uptake in rat brain. Adult male Wistar rats
      were administered trimetazidine (Metazydyna, Polfa) either as a single dose (10.0
      mg/kg po) or for 14 consecutive days (5.0 mg/kg po per day) or vehicle saline
      (2.0 ml/kg po). Sixty minutes after the single dose or 14th dose of
      trimetazidine, and 15 min before experiment termination and brain dissection, 6
      [(3)H]D-glucose (500 Ci/kg ip; Amersham) was administered. Using liquid
      scintillation counting, trimetazidine, either in a single or multiple dose
      regimen, was found to increase [(3)H]glucose uptake (DPM/100 mg of wet tissue) in
      all dissected regions of the brain (i.e., striatum, hippocampus, frontal cortex,
      thalamus with hypothalamus, pons with medulla oblongata, and cerebellum).
      Therefore, central effects need to be taken into consideration as possibly adding
      to known beneficial cardiac effects of trimetazidine.

PMID- 16963804
TI  - Influence of long-term treatment with tuftsin analogue TP-7 on the anxiety-phobic
      states and body weight.
AB  - TP-7 is a synthetic analogue of tuftsin. It has a structure of tuftsin, to which
      three natural L-amino-acids Pro-Gly-Pro are attached. This heptapeptide improves
      learning and memorization and causes antidepressant and anxiolytic effect. It is
      possible to use TP-7 in the future to optimize cognitive functions and as a
      potential new anxioselective, fast-acting and easy-dosed drug. Therefore, it was
      purposeful to study such properties of the heptapeptide as its influence on
      anxiety-fear and body weight under a long-term treatment regimen. The experiment
      was performed on 24 preselected Wistar rats with the use of Rodina's method.
      There were three experimental groups of animals with high initial emotional
      reactivity: passive control group (P), active control group (A, receiving
      distilled water) and group treated with TP-7 at the dose of 0.3 mg/kg (T). The
      rats of A and T groups received intraperitoneal injections every day. The
      experiments were conducted 15 min after the administration of the drug, one and
      two days after initial testing day, then 1, 2, 3 and 4 weeks after that. The
      heptapeptide reduced the anxiety-phobic states significantly starting from the
      second day of drug application. The observed effects persisted throughout four
      weeks of the experiment, which confirmed effective long-term anxiolytic
      properties of the heptapeptide. TP-7 did not cause any changes in the body mass
      by itself.

PMID- 16963805
TI  - Anxiolytic effect of noscapine in mice.
AB  - The anxiety-related effects of noscapine were investigated using male Balb-c
      mice. Since noscapine-induced locomotion may alter the animals' activity level in
      the dark-light model, the anxiety-related effects of noscapine were studied at
      doses with no effect on locomotion (0.1, 0.2, 0.3, 0.4, 0.5, 0.8, 1, 1.5 and 2
      mg/kg). The parameter measured in dark-light model was the time spent in lit
      compartment. Intraperitoneal administration of noscapine (0.1-0.5 mg/kg) did not
      produce a significant effect on the time spent in the light, whereas higher doses
      (0.8, 1, 1.5 and 2 mg/kg) increased it significantly, implying an anxiolytic
      effect.

PMID- 16963806
TI  - Antepartum/postpartum depressive symptoms and serum zinc and magnesium levels.
AB  - In the present study, we investigated the relationship between depressive
      symptoms and serum zinc and magnesium level in antepartum and postpartum women.
      All women received standard vitamin, zinc and magnesium supplementation. Sixty
      six pregnant women in the Czerwiakowski Hospital in Krakow were assessed for
      prepartum depressive symptoms using the Beck Depression Inventory (BDI). Sixty
      two and fifty-eight women were also assessed for postpartum depressive symptoms
      (using Edinburgh Postnatal Depression Rating Scale, EPDRS) at 3 and 30 days after
      delivery, respectively. Serum zinc and magnesium levels were also determined at
      these time points, however, the number of examined subjects were diminished. A
      significantly higher EPDRS score (by 45%), indicating severity of depressive
      symptoms, was found on the 3rd day after childbirth compared with the 30th
      postpartum day. Moreover, the early post-delivery period (3rd day) was
      characterized by a 24% lower serum zinc concentration than that found on the 30th
      day after childbirth. BDI scores assessed a month before childbirth revealed mild
      depressive symptoms, which was accompanied by a serum zinc concentration similar
      to that found on the 3rd day after delivery. No significant alterations were
      found in the magnesium levels between these time points. The present results
      demonstrated a relationship between severity of depressive symptoms and decreased
      serum zinc (but not magnesium) concentration in a very specific type of affective
      disorder, the postpartum depression.

PMID- 16963808
TI  - The art and science of introducing animals to the research environment.

PMID- 16963807
TI  - Regulation of LDL receptor expression by the effect of curcumin on sterol
      regulatory element pathway.
AB  - To investigate the molecular mechanisms of the effect of curcumin on up
      regulation of LDL receptor expression, a sterol regulatory report system was
      established in Xenopus laevis oocytes by microinjection of a plasmid pLXRN-4SRE
      fPA, in which green fluorescence protein (GFP) gene was constructed downstream
      from the sterol regulatory element-1 (SRE-1), in the nucleus of the oocytes. The
      oocytes were treated with different kinds of natural medicines: curcumin, tea
      polyphenols, tanshinone, ligustrazine, ginkgolide, astragalosides. The expression
      of GFP was induced only by curcumin. In addition, it was also proved that the
      curcumin can increase the expression of functional LDL receptors in human liver
      hepatoma cell line HepG2. In conclusion, curcumin may up-regulate the expression
      of LDL receptor by its effect on SRE pathway.

PMID- 16963809
TI  - Preparation of animals for research--issues to consider for rodents and rabbits.
AB  - This article provides details to consider when preparing to use animals in
      biomedical research. The stress of transport and receipt of animals into a new
      environment mandate the need for a period of stabilization and acclimation. This
      allotment of time often occurs in conjunction with the quarantine period and
      permits a stress "recovery" period. Discussions in the article include specific
      effects of the environment on the animal, such as housing and environmental
      enrichment. Suggestions are offered regarding how to minimize the effects of
      procedures and equipment through the use of preconditioning techniques.
      Guidelines for these techniques and for acclimation should be instituted by the
      institutional animal care and use committee. Stress and distress are placed in
      perspective as they relate to the preparation of laboratory animals for research.

PMID- 16963810
TI  - Considerations in the selection and conditioning of Old World monkeys for
      laboratory research: animals from domestic sources.
AB  - Nonhuman primates from domestic sources constitute an important resource for the
      research community. The life history of the Old World monkey species that
      comprise the bulk of this resource is described, and issues that colony managers
      and researchers alike should consider regarding animal selection (e.g., species,
      age, sex, rearing history, temperament, genotype, viral status, geographic
      origin) are discussed. Preparation of domestically bred animals for research
      usually involves some combination of social separation, relocation,
      resocialization, alterations in physical space, photoperiod, and diet, as well as
      exposure to novel environments. The research literature that has focused on these
      issues is reviewed, and authors suggest that once animals have been assigned to
      their project housing situation, a period ranging up to 3 mo (depending on the
      magnitude of the change in housing) might be warranted before an experimental
      protocol should begin. Attention to issues of animal selection and conditioning
      by both researchers and colony managers can lead to the shared goal of high
      quality research that utilizes the minimal number of animals.

PMID- 16963811
TI  - Preparing New World monkeys for laboratory research.
AB  - New World monkeys represent an important but often poorly understood research
      resource. The relatively small size and low zoonotic risk of these animals make
      them appealing as research subjects in a number of areas. However, historic
      portrayal of many of these species as difficult to manage and handle is one of
      the factors that has limited their use. Basic guidelines are provided on
      management and handling approaches for the New World monkeys most commonly used
      in research: marmosets, squirrel monkeys, owl monkeys, and titi monkeys. Topics
      include transport and acclimation to a new facility, location changes within a
      facility, diet changes, removal from and return to social groups, capture and
      restraint, handling for anesthesia, postprocedural monitoring, and staff
      training.

PMID- 16963812
TI  - Preparing chimpanzees for laboratory research.
AB  - The chimpanzee is the only representative of the Great Apes that is extensively
      involved in biomedical research in primate laboratories. These apes are used as
      animal models in a variety of studies, including research on infectious disease,
      parasitic disease, pharmacokinetic studies, neuroscience, cognition, and
      behavior. Chimpanzees used in biomedical research in the United States reside
      largely in six specialized research and holding facilities, and most of the
      research with them is conducted at these sites. Given the relatively small
      population of chimpanzees and its importance to biomedical research, it is
      imperative that we carefully manage the care, production, and use of these
      animals in biomedical research studies. Selection criteria and preparation
      techniques are reviewed in this article in an effort to begin a discussion on
      best practices for choosing and handling chimpanzees participating in biomedical
      research. The use of routine health assessment information is described for
      subject selection, as are behavioral issues to be considered. Due to the
      relatively small number of chimpanzees available, issues related to experimental
      design and multiple uses of chimpanzees are discussed. Practices related to the
      transportation and acclimation of chimpanzees are described. Finally, behavioral
      conditioning procedures are discussed, including habituation, desensitization,
      and positive reinforcement training that have been applied to reduce animal
      distress and improve the quality of the science being conducted with chimpanzee
      subjects.

PMID- 16963813
TI  - Selection, acclimation, training, and preparation of dogs for the research
      setting.
AB  - Dogs have made and will continue to make valuable contributions as animal models
      in biomedical research. A comprehensive approach from time of breeding through
      completion of in-life usage is necessary to ensure that high-quality dog models
      are used in studies. This approach ensures good care and minimizes the impact of
      interanimal variability on experimental results. Guidance related to choosing and
      developing high-quality laboratory dogs and managing canine research colonies is
      provided in this article. Ensuring that dogs are healthy, well adapted, and
      cooperative involves good communication between vendors, veterinarians, care
      staff, and researchers to develop appropriate dog husbandry programs. These
      programs are designed to minimize animal stress and distress from the postweaning
      period through the transfer and acclimation period within the research facility.
      Canine socialization and training programs provided by skilled personnel,
      together with comprehensive veterinary health programs, can further enhance
      animal welfare and minimize interanimal and group variability in studies.

PMID- 16963814
TI  - Issues to consider for preparing ferrets as research subjects in the laboratory.
AB  - The domestic or European ferret (Mustela putorius furo) has been domesticated for
      thousands of years. Ferrets have been used for hunting and fur production, as
      pets, and as models in biomedical research. Despite the relatively small numbers
      used in the laboratory, ferrets have some unique applications including study of
      human influenza and severe acute respiratory syndrome (SARS)-associated corona
      virus. They have served as models for peptic ulcer disease, carotenoid
      metabolism, cystic fibrosis, and drug emesis screening, among others. Most
      research ferrets are males, due to estrus-related health problems in females.
      They may be housed conventionally and are easy to care for when their biology and
      behavior are understood. Due to the small number of ferret suppliers, animals are
      often shipped long distances, requiring air transport and intermediate handlers.
      It is important to minimize shipment stress, especially with weanling and
      pregnant animals. Additional expertise is required for success with pregnant and
      whelping ferrets and for rearing of neonates. The animals have specific dietary
      requirements, and proper nutrition is key. Successful housing requires knowledge
      of ferret behaviors including social behavior, eating habits, a general
      inquisitive nature, and a species-typical need to burrow and hide. Regular
      handling is necessary to maintain well-being. A ferret health care program
      consists of physical examination, immunization, clinical pathology, and a working
      knowledge of common ferret diseases. Various research methodologies have been
      described, from basic procedures such as blood collection to major invasive
      survival surgery. Ferrets have a distinct niche in biomedical research and are
      hardy animals that thrive well in the laboratory.

PMID- 16963815
TI  - Preparation of swine for the laboratory.
AB  - Swine are an important model in many areas of biomedical research. These animals
      have been used predominantly as preclinical models involving surgical and
      interventional protocols. The systems most commonly studied include
      cardiovascular, integumentary, digestive, and urological. Swine are intelligent
      social animals and require species-specific socialization and handling
      techniques. It is important to acclimate the animals to the facility and to
      personnel before they are placed on chronic protocols. Gentle handling techniques
      instead of forceful procedures are essential to their socialization. They require
      sturdy caging with specific construction standards, and toys for environmental
      enrichment. Because the species is covered by both the Animal Welfare Act and the
      US Department of Agriculture, interstate transport requires a health certificate
      with destination state-specific disease screening standards. This manuscript
      provides an overview of best practices that have been utilized in the authors'
      facility.

PMID- 16963816
TI  - Establishing an appropriate period of acclimatization following transportation of
      laboratory animals.
AB  - Stress associated with transportation has widespread effects on physiological
      systems in laboratory animals, including changes in the cardiovascular,
      endocrine, immune, central nervous, and reproductive systems. Although short
      lived, these changes can confound research if animals are utilized before
      homeostasis is restored and physiological measures return to normal. Therefore,
      some period of acclimatization following transportation is generally suggested to
      restore homeostasis. The following two questions should be considered to
      establish an adequate period for acclimatization: (1) Will anticipated
      physiological changes confound the research to be conducted? (2) What is the
      length of time necessary for confounding physiological changes to normalize?
      Finding answers to those questions in the literature can be a challenge. Most
      literature on the physiological impact of transportation involves agricultural
      animals, although the limited literature in common laboratory animal species
      generally parallels changes documented in agricultural animals. The literature
      documents elevated heart rate and weight loss, as well as elevated concentrations
      of adrenaline, noradrenaline, glucose, cortisol, free fatty acids, and beta
      hydroxybutyrate. Carbohydrate, protein, and lipid metabolism (both lipolysis and
      lipogenesis) are altered, and plasma osmolality, albumen, protein, and pack-cell
      volume increase. Neutrophilia and lymphopenia are also evident. These measures
      generally return to baseline within 1 to 7 days of transportation, although
      animals that are young, severely stressed, and have stress-sensitive genotypes
      may show altered physiological measures for several weeks. Other measures such as
      circadian rhythm and reproductive performance may take several weeks to months to
      normalize.

PMID- 16963817
TI  - Preparation of animals for use in the laboratory: issues and challenges for the
      Institutional Animal Care and Use Committee (IACUC).
AB  - Preparation of animals is important for optimization of animal welfare as well as
      to minimize interanimal variation, thereby strengthening the quality of data for
      in vivo studies. These issues are important in the work of institutional animal
      care and use committees (IACUCs), but they pose many challenges as well. This
      article provides IACUC members with a resource for use in determining whether and
      how preparation of animals for research affects the IACUC's responsibilities. The
      topics addressed are intended to serve as a starting point for consideration and
      discussion. Questions related to subject selection and acclimation of subjects to
      experimental housing and procedures are emphasized and should provide IACUC
      members with a framework for discussion of relevant questions. Guidelines are
      provided for promoting the acclimation of a number of species to experimental
      settings. Additional, potentially controversial points are also raised, including
      the effects on longitudinal data sets of changing subject preparation procedures.
      The roles of the IACUC in the research endeavor are multifaceted and continuously
      evolving. As empirical data are produced that affect additional aspects of animal
      care and use, it is important for these committees to be able to evaluate and,
      when appropriate, stimulate the implementation of improved procedures and
      strategies.

PMID- 16963818
TI  - En-masse distalization with miniscrew anchorage in Class II nonextraction
      treatment.

PMID- 16963819
TI  - Class III nonextraction treatment with miniscrew anchorage.

PMID- 16963821
TI  - Controlling erupted and unerupted permanent teeth in the mixed dentition with
      preadjusted appliances.

PMID- 16963823
TI  - A modified rapid palatal expander for correction of anterior open bite and
      posterior crossbite.

PMID- 16963822
TI  - Four-premolar extraction treatment with Invisalign.

PMID- 16963824
TI  - Easy-to-bond lower lingual retainer.

PMID- 16963825
TI  - Phyto- and endogenous estrogens differently activate intracellular calcium ion
      mobilization in bovine endometrial cells.
AB  - The main purpose of this study was to check whether phyto- and endogenous
      estrogens influence calcium ion mobilization [Ca(2+)](i) in bovine endometrial
      cells and whether this action is connected with biological effects i.e.
      prostaglandin (PG)F(2alpha) production. In our study we used two calcium
      measurement methods by comparing the microscopic method with widely used
      quantitative - spectrofluorometric method of [Ca(2+)](i) measurement. We also
      wanted to confirm whether visualization of calcium ion [Ca(2+)](i) in cells using
      microscopic method supported by micro image analysis (Micro Image Olympus system)
      reflects real, qualitative changes in the ion concentration. In both methods a
      cell-permeable form of fluorescent [Ca(2+)](i) indicator Fura-2 was used.
      Cultured bovine endometrial epithelial and stromal cells influenced by phorbol-2
      myristate-13-acetate (PMA; positive control), estradiol 17-beta (E(2); endogenous
      estrogen) and active metabolites of phytoestrogens (environmental estrogens) were
      used as a model to study PGF(2alpha) secretion and [Ca(2+)](i) mobilization in
      the cells. Equol and para-ethyl-phenol in doses of 10(-8)-10(-6) M increased
      PGF(2alpha) concentration both in epithelial and stromal cells (P<0.05). In both
      methods, equol and para-ethyl-phenol did not cause intracellular [Ca(2+)](i)
      mobilization in epithelial and stromal cells (P>0.05). Both methods revealed that
      only E(2) and PMA induced intracellular [Ca(2+)](i) mobilization in epithelial
      and stromal cells (P<0.05). The results of both methods were highly correlated
      (P<0.001; r=0.82 for epithelial cells and r=0.89 for stromal cells). In
      conclusion, both methods gave approximately the same results and showed that
      phytoestrogens, in contrast to PMA and E(2), did not cause intracellular
      [Ca(2+)](i) mobilization in endometrial cells. The obtained results proved that
      the [Ca(2+)](i) visualization method supported by micro image analysis can
      produce similar results to the spectrofluorometric method.

PMID- 16963826
TI  - The relationship between general osteoporosis of the organism and periodontal
      diseases.
AB  - Osteoporosis and periodontitis are very prevalent diseases and are most common in
      middle-aged and elderly women. These diseases are related as both damage bone
      tissue and share common risk factors. Discussions about the association between
      these two bone-damaging diseases began in 1960. A hypothesis was raised that
      systemic imbalance in bone resorption and deposition might manifest itself in the
      alveolar bone earlier than in other bones. When analyzing systemic and local
      changes in bone density, a number of issues were investigated and attempted to
      answer the question of whether dental osteopenia is a local manifestation of
      osteoporosis having similar etiology and risk factors, or it is an independent
      process depending primarily on factors that cause periodontal disease.
      Histomorphometric and microradiographic studies showed that increasing porosity
      of the cortical layer in mandible resulted in the decrease in bone mass. Bone
      strength is best expressed through bone mineral density, and it can be called a
      diagnostic criterion of osteoporosis. The examination of bone mineral density is
      called densitometry and may be performed using dual-energy x-ray absorptiometry.
      Orthopantomography is a method that is widely applied in odontological practice
      and is also informative in determining the bone density of the mandible. It can
      be applied when performing orthopantomographic and vertical linear measurements,
      as well as in determining indices in the studies of osteoporotic changes. Since
      many patients attend odontological clinics, nearly all of them undergo
      orthopantomography. This is a good possibility to investigate osteoporotic
      changes in the mandible, to select individuals for further studies, and to ensure
      clinical benefit and good treatment results.

PMID- 16963827
TI  - Scientific problems of photosensitivity.
AB  - Photosensitive skin reactions occur when human skin reacts to ultraviolet
      radiation or visible light abnormally. The forms of photosensitivity are
      phototoxicity and photoallergy. Phototoxic disorders have a high incidence,
      whereas photoallergic reactions are much less frequent in human population.
      Several hundred substances, chemicals, or drugs may invoke phototoxic and
      photoallergic reactions. In order to avoid photosensitive reactions it is
      essential to determine the photosensitizing properties of such substances before
      drugs are introduced in therapy or products made available on the market. The
      article reviews the mechanisms of photosensitization, explains the most important
      differences between phototoxic and photoallergic reactions, summarizes the most
      common photosensitizers, and presents the clinical features and diagnostic
      procedures of phototoxic and photoallergic reactions.

PMID- 16963828
TI  - Effects of ketamine on precipitated opiate withdrawal.
AB  - OBJECTIVE: N-methyl-D-aspartate antagonists were shown to be effective in
      suppressing the symptoms of opiate withdrawal. Intravenous anesthetic, ketamine,
      is the most potent N-methyl-D-aspartate antagonist available in clinical
      practice. The present study was designed to evaluate the effects of subanesthetic
      ketamine infusion, as little human data are available on ketamine in precipitated
      opiate withdrawal. MATERIALS AND METHODS: A total of 58 opiate-dependent patients
      were enrolled in a randomized, placebo-controlled, double-blind study. Patients
      underwent rapid opiate antagonist induction under general anesthesia. Prior to
      opiate antagonist induction patients were given either placebo (normal saline) or
      subanesthetic ketamine infusion of 0.5 mg/kg/h. Further evaluations were divided
      into three phases: anesthetic, early postanesthetic (48 hours), and remote at 4
      months after procedure. Cardiovascular, respiratory, renal, and gastrointestinal
      responses to opiate antagonist induction were monitored during anesthesia phase.
      Changes in plasma cortisol concentrations were measured as stress-response
      markers. Evaluations during early postanesthetic phase were based on Subjective
      and Objective Opiate Withdrawal Scales. Remote effects were assessed according to
      questionnaire based on Addiction Severity Index. RESULTS: Altogether, 50 patients
      were included in the final analysis. Ketamine group presented better control of
      withdrawal symptoms, which lasted beyond ketamine infusion itself. Significant
      differences between Ketamine and Control groups were noted in anesthetic and
      early postanesthetic phases. There were no differences in effects on outcome
      after 4 months. CONCLUSION: In this study, subanesthetic ketamine infusion was an
      effective adjuvant in the correction of acute precipitated opiate withdrawal
      although it had no long-term effects on treatment of opiate dependence.

PMID- 16963829
TI  - [Pediatric disability of the upper extremity and quality of life questionnaire:
      reliability, validity, and sensitivity to change].
AB  - OBJECTIVE: The aim of this study was to develop a specific questionnaire,
      designed to evaluate health-related quality of life of children and adolescents
      with congenital or acquired anomalies of the upper extremity. MATERIAL AND
      METHODS: Children who underwent operative or conservative treatment of the upper
      extremity at Kaunas University of Medicine Hospital and Kaunas Red Cross Hospital
      or conservative treatment at Kaunas Sanatorium "Zibute" and Druskininkai
      Sanatorium "Saulute" participated in the study. A total of 99 parents and 56
      adolescents with congenital or acquired anomalies of the upper extremity filled
      out the questionnaires. The data were analyzed by the program SPSS 12.0.1 for
      Windows. RESULTS: Two versions of questionnaire were developed: one for parents
      of children and adolescents aged 5-18 years and another - for adolescents aged 11
      18 years. Both versions consist of seven scales: self-care, daily activities,
      sports activities and hobby, self-image, emotional, social health, and patient's
      satisfaction with treatment. The testing of questionnaire reliability was
      performed by estimating a Cronbach alfa coefficient which varied from 0.80 to
      0.97 for different scales of questionnaire designed for parents. The item-scale
      correlation was from 0.44 to 0.89. There was a statistically significant
      difference among separate items for all scales (p<0.001). The intraclass
      correlation coefficient ranged from 0.84 to 0.89 for all scales. Cronbach alfa
      coefficients of scales of questionnaire designed for children varied from 0.83 to
      0.95, and item-scale correlation was moderate to strong. A statistically
      significant difference among separate items for all scales was obtained
      (p<0.001). The intraclass correlation coefficient varied from 0.79 to 0.86. The
      Pearson's correlation coefficient between questionnaires developed for parents
      and children was calculated, and strong correlation between corresponding scales
      was found. Sensitivity to changes was tested, and t-test was performed. A
      statistically significant difference in all scales was found (p<0.001).

PMID- 16963830
TI  - [Pneumocystis jirovecii pneumonia: an old disease with a new name].
AB  - Pneumocystis jirovecii pneumonia has historically been one of the most common
      opportunistic pneumonias and life-threatening infectious complications in HIV
      infected patients. After the introduction of combination antiretroviral therapy,
      the incidence of Pneumocystis pneumonia and other opportunistic infections has
      decreased dramatically. Nowadays Pneumocystis pneumonia still occurs in patients
      unaware of their HIV status, in those not receiving combination antiretroviral
      therapy, or in those in whom it is ineffective due to resistance. Age factor is
      the diagnosis delaying one: patients aged more than 50 years are diagnosed with
      AIDS later than younger persons. Pneumocystis was thought to be a species of
      protozoa. Over the last 20 years, Pneumocystis has been shown to be a fungus, to
      be genetically diverse, host species specific, to colonize individuals with minor
      immunosuppression, and to cause clinical disease by "new" infection in addition
      to reactivation of latent childhood-acquired infection. Recently, the
      microorganism Pneumocystis carinii causing disease in humans has been renamed to
      Pneumocystis jirovecii. This article presents a clinical case of late diagnosis
      of Pneumocystis jirovecii pneumonia in a 62-year-old patient unaware of her HIV
      status and a review of literature reflecting epidemiological issues of
      Pneumocystis jirovecii and latest discoveries related to Pneumocystis as well as
      the rationale for renaming it.

PMID- 16963831
TI  - [A case of severe hyponatremia in a patient suffering from epilepsy and using
      oxcarbazepine].
AB  - A 70-year-old patient treated with oxcarbazepine experienced severe hyponatremia.
      The patient used oxcarbazepine (600 mg twice a day) concomitantly with diuretics
      (torasemide 10 mg and indapamide 1.25 mg once per day), perindopril, an
      angiotensin-converting enzyme inhibitor, and amlodipine, a Ca(2+) channel
      blocker. The patient complained of a nausea, malaise, diplopia, drowsiness,
      apathy, decreased diuresis (creatinine clearance - 41.51 ml/min), and
      exacerbation of epileptic seizures. Sodium concentration in the plasma was 113
      mmol/l. The patient was hospitalized. It was suggested that a decrease in plasma
      sodium concentration was caused by oxcarbazepine used together with diuretics for
      six months. Oxcarbazepine-induced hyponatremia is reported in 22.2-50% of
      patients, although symptoms are present only in 5.9% of patients. The most common
      symptoms of central nervous system injury, experienced by patients, are
      drowsiness, dizziness, decreased cognitive function, coordination impairment,
      etc. Physicians not always in time pay proper attention to undesirable
      antiepileptic drug-induced effects, which can be dangerous.

PMID- 16963832
TI  - Power of performance of the thumb adductor muscles: effect of laterality and
      gender.
AB  - The aim of this work was to originally measure mechanical power output of the
      thumb adductor muscles during fast adduction of the thumb in the horizontal
      plane. This information will contribute to biomechanical guidelines to help
      clinicians, sport medicine and rehabilitation specialists in the objective
      functional evaluation of abnormalities of thumb adductors. Participants performed
      20 fast adductions in response to audio signals. Maximum and average angular
      velocity and angular acceleration were measured. Tangential components of these
      parameters were then derived. The force of adduction was obtained from the
      tangential acceleration and the mass of the rotational system. The power was then
      calculated as the product of the force of adduction and average tangential
      velocity during the acceleration phase of adduction. All young and untrained
      males and females were strictly right handed. There was no significant difference
      in power between dominant and nondominant muscles for either males or females,
      but males developed significantly more power than females. Because adduction was
      performed at maximal speed, these data may be explained by the influence of
      parallel and series elastic elements in the muscle, as well as by influence of
      fast twitch fibers. Power may be used as a clinical index of the effectiveness of
      muscle contraction. The similarity of power outputs from dominant and nondominant
      thumb adductor muscles of right-handers can suggest a classical Bernstein
      approach. This theoretical approach purports that peripheral factors can distort
      central commands projected to dominant and nondominant extremities.

PMID- 16963833
TI  - The effect of long-term swimming program on body composition, aerobic capacity
      and blood lipids in 14-19-year aged healthy girls and girls with type 1 diabetes
      mellitus.
AB  - OBJECTIVE: To evaluate the effect of long-term swimming program on body
      composition, aerobic capacity, and blood lipid/cholesterol level. MATERIAL AND
      METHODS: Nineteen girls aged 14-19 years with duration of diabetes of 8.1+/-0.9
      years and 28 healthy girls aged 14-19 years participated in the study. Before and
      after 14-week swimming program, weight, height, and four skinfold thickness were
      measured, body mass index (kg/m(2)) and body fat mass (%) were calculated, blood
      lipid levels (total cholesterol, high-density/low-density lipoprotein, and
      triglyceride) were estimated. Aerobic capacity was assessed by Ruffie test.
      Training sessions (each lasted for 45 min) were held twice per week for 14 weeks.
      A total of 28 trainings were performed in the swimming pool. Workload intensity
      was corrected by pulse measurement before and after every session in the water.
      RESULTS: After 14-week swimming program, body mass index did not change, but body
      fat mass decreased significantly in healthy (27.2+/-1.0 vs. 25.5+/-0.8%, p<0.001)
      and diabetics (34.8+/-1.2 vs. 32.1+/-1.2%, p<0.001) subjects. Both groups
      improved their aerobic capacity (p<0.01 in healthy and p<0.05 in diabetics). No
      significant changes in blood lipid profile were found in all subjects, only high
      density lipoprotein concentration significantly increased in healthy girls
      (p<0.001). CONCLUSION: Long-term swimming program improved aerobic capacity,
      reduced body fat mass in all participants, and reduced high-density lipoprotein
      levels only in healthy subjects.

PMID- 16963834
TI  - The influence of meteorological factors on growth and vegetation process of
      Perilla frutescens (L.) Britton in Lithuania.
AB  - The results of a study on the dependence of growth and vegetation process of
      Perilla frutescens (L.) Britton upon meteorological factors are presented in the
      article. The investigations were conducted at Kaunas Botanical Garden of Vytautas
      Magnus University during vegetation periods in 2001-2005. The object of
      investigations was Perilla frutescens (L.) Britton, a medicinal annual herbaceous
      plant of Lamiaceae Lindl. family, native of Eastern Asia, which passes the whole
      development cycle under climatic conditions of Central Lithuania. The duration of
      vegetation period of Perilla frutescens on the average is 167 days. The earliest
      beginning of vegetation and optimal climatic conditions for growth are when
      hydrothermic coefficient reaches 1.60-1.80 (conditions of excessive humidity).
      Optimal climatic conditions for massive flowering and seed maturation are
      observed when hydrothermic coefficient decreases to 1.20 - then massive flowering
      starts 10 days earlier and lasts 25 days longer. A strong correlation was found
      between massive flowering and hydrothermic coefficient (r(2)=0.9408). Using
      mathematical-statistical methods, the consistent patterns of growth and
      vegetation process of Perilla frutescens (L.) Britton were determined, specifying
      the time for raw material preparation what determines its quality and quantity.

PMID- 16963835
TI  - Delboeuf illusion study.
AB  - In psychophysical experiments, the Delboeuf illusion was measured as a function
      of spatial parameters of the stimulus pattern. During the experiments, the
      stimulus shape, size, luminance, and the dimensions of inducing surround varied.
      Subjects were asked to change the size of the test part of the stimulus by
      adjusting its diameter to value that made the test part appear equal to the
      perceived size of the referent part. The difference in diameters between the test
      and referent parts of the stimulus, determined after the perceived equality was
      achieved, was considered to be the value of the illusion magnitude. The magnitude
      of the Delboeuf illusion was dependent on the type of the stimuli and their
      contrast: the filled circles with the luminance contrast yielded stronger
      illusion than the open circles and the stimuli with isoluminant colors. The
      magnitude of the illusion did not change noticeably with variations of the
      luminance of the stimulus, but diminished when the luminance of the stimulus
      approached the level of isoluminance with the background. The neurophysiological
      spatial filtering model, applied to the Delboeuf stimuli patterns, has provided
      computational results similar to the present experimental findings.

PMID- 16963836
TI  - [Acute heart failure].
AB  - There are still many discussions among physicians how heart failure should be
      defined. Despite many suggested traditional classifications, majority of
      definitions circulating in clinical practice and their appropriate usage remain
      unclear. A new approach of acute heart failure classification suggested by
      European Society of Cardiology is presented in the article. Diagnostic strategy
      of acute heart failure as well as recommendations for prehospital and inpatient
      treatment of its forms (pulmonary edema and cardiogenic shock) are presented in
      the article. Application of new medications, recently introduced to the clinical
      practice for treatment of acute heart failure, is discussed.

PMID- 16963837
TI  - Essential role for activation of the Polycomb group (PcG) protein chromatin
      silencing pathway in metastatic prostate cancer.
AB  - The Polycomb group (PcG) gene BMI1 is required for the proliferation and self
      renewal of normal and leukemic stem cells. Overexpression of Bmi1 oncogene causes
      neoplastic transformation of lymphocytes and plays essential role in pathogenesis
      of myeloid leukemia. Another PcG protein, Ezh2, was implicated in metastatic
      prostate and breast cancers, suggesting that PcG pathway activation is relevant
      for epithelial malignancies. Whether an oncogenic role of the BMI1 and PcG
      pathway activation may be extended beyond the leukemia and may affect progression
      of solid tumors as well remains unknown. Here we demonstrate that activation of
      the BMI1 oncogene-associated PcG pathway plays an essential role in metastatic
      prostate cancer, thus mechanistically linking the pathogenesis of leukemia, self
      renewal of stem cells, and prostate cancer metastasis. To characterize the
      functional status of the PcG pathway in metastatic prostate cancer, we utilized
      advanced cell- and whole animal-imaging technologies, gene and protein expression
      profiling, stable siRNA-gene targeting, and tissue microarray (TMA) analysis in
      relevant experimental and clinical settings. We demonstrate that in multiple
      experimental models of metastatic prostate cancer both BMI1 and Ezh2 genes are
      amplified and gene amplification is associated with increased expression of
      corresponding mRNAs and proteins. For the first time, we provide images of human
      prostate carcinoma metastasis precursor cells isolated from blood and shown to
      overexpress both BMI1 and Ezh2 oncoproteins. Consistent with the PcG pathway
      activation hypothesis, increased BMI1 and Ezh2 expression in metastatic cancer
      cells is associated with elevated levels of H2AubiK119 and H3metK27 histones.
      Quantitative immunofluorescence colocalization analysis and expression profiling
      experiments documented increased BMI1 and Ezh2 expression in clinical prostate
      carcinoma samples and demonstrated that high levels of BMI1 and Ezh2 expression
      are associated with markedly increased likelihood of therapy failure and disease
      relapse after radical prostatectomy. Gene-silencing analysis reveals that
      activation of the PcG pathway is mechanistically linked with highly malignant
      behavior of human prostate carcinoma cells and is essential for in vivo growth
      and metastasis of human prostate cancer. We conclude that the results of
      experimental and clinical analyses indicate the important biological role of the
      PcG pathway activation in metastatic prostate cancer. Our work suggests that the
      PcG pathway activation is a common oncogenic event in pathogenesis of metastatic
      solid tumors and provides justification for development of small molecule
      inhibitors of the PcG chromatin silencing pathway as a novel therapeutic modality
      for treatment of metastatic prostate cancer.

PMID- 16963838
TI  - Evidence for selective mitochondrial autophagy and failure in aging.
AB  - Autophagy is a major intracellular degradation/recycling system ubiquitous in
      eukaryotic cells. It contributes to the turnover of cellular components by
      delivering portions of the cytoplasm and organelles to lysosomes, where they are
      digested. Starvation-induced autophagy is required for maintaining an amino acid
      pool for gluconeogenesis and for the synthesis of proteins essential to survival
      under starvation conditions. In addition, autophagy plays an important role in
      the degradation of excess or injured organelles, including mitochondria. To test
      the hypothesis of an involvement of a decrease in autophagy in the process of
      aging, we explored the antiaging effects of pharmacological stimulation of
      autophagy on the age-dependent accumulation of 8-OHdG-rich mitochondria in rat
      liver. Male 3-month and 16-month-old 24 hours-fasted Sprague Dawley rats were
      injected with the antilipolytic agent [3,5-dimethylpyrazole (DMP)]
      intraperitoneally. Results showed that drug injection rescued older cells from
      the accumulation of 8-OHdG in the mtDNA in less than 6 hours, but no significant
      decrease in the level of cytochrome c oxidase activity was observed. Together,
      these data provide indirect evidence that 8-OHdG might accumulate in a small pool
      of mitochondria with increasing age rather than be degraded by the autophagic
      machinery selectively.

PMID- 16963839
TI  - Transcriptional activation of the carboxylesterase 2 gene by the p53 pathway.
AB  - The p53 tumor suppressor is an important regulator of cellular response to
      chemotherapeutic agents by virtue of the protein's ability, upon activation by
      phosphorylation, to transcriptionally activate a number of genes involved in cell
      proliferation, apoptosis, and metabolism. Transcriptome analysis following
      introduction of a constitutively active form of p53 (p53T18D/S20D) into colon
      carcinoma cell lines identified transcriptional activation of the
      carboxylesterase 2 (CES-2) gene, which is involved in drug metabolism. We
      examined whether p53 activated by the DNA-damaging drug 5-fluorouracil (5-FU)
      also induces CES-2 expression. Our experiments showed that 5-FU induced CES-2
      expression in two colon carcinoma cell lines that express wild-type p53 (HCT116
      p53(+/+) and RKO) but not in five lines that are p53-null (HCT116 p53(-/- )) or
      express mutated p53 (HT29, KM12C, KM12SM, and KM12L4A). Sequence analysis
      revealed a putative p53-binding element in the first intron of CES-2 that
      differed from consensus by one nucleotide. A reporter gene assay showed that the
      luciferase construct with the p53-binding element responded to 5-FU treatment,
      whereas the reporter construct without the binding element did not. Chromatin
      immunoprecipitation assay confirmed that p53 bound the CES-2 fragment containing
      the p53-binding element after 5-FU treatment, whereas p21 binding to p53 was
      present with or without chemotherapy. Knockdown of expression of CES-2 and p53 by
      small interference RNA in RKO and HCT116 p53(+/+) cells attenuated the anti
      proliferation effects of CPT11. These results taken together show that activated
      p53 directly regulates CES-2 expression via a p53-binding site, representing a
      novel mechanism through which the p53 pathway modulates drug metabolism. In
      addition, the degree of homology in the p53-binding element may determine the
      strength of p53 regulation.

PMID- 16963840
TI  - Stimulation of ATG12-ATG5 conjugation by ribonucleic acid.
AB  - The ubiquitin-like conjugation reactions, ATG8/microtubule-associated protein 1
      light chain 3/MAP1LC3 (LC3) to phosphatidylethanolamine (PE) and ATG12 to ATG5,
      are biochemical hallmarks for autophagy, a cellular process that degrades bulk
      cellular proteins and organelles. The two conjugation reactions share the same E1
      like enzyme ATG7 but have different E2-like enzymes, ATG3 for LC3-PE and ATG10
      for ATG12-ATG5. In cells, ATG12-ATG5 conjugation appears to be required for LC3
      PE conjugation. Previously, in vitro reconstitution of LC3-PE conjugation, but
      not the upstream ATG12-ATG5 conjugation, was reported. In this study, we describe
      for the first time the de novo reconstitution of mammalian ATG12-ATG5 conjugation
      by using purified recombinant proteins. We show that ATG7, ATG10 and ATP as an
      energy source are all essential for ATG12-ATG5 conjugation, and mutation of the
      specific lysine residue of ATG5 for ATG12 conjugation abrogates the reaction.
      Furthermore, a potent stimulating activity for ATG12-ATG5 conjugation was
      detected in mammalian cell extracts, and was surprisingly identified as
      ribosomes. Our detail biochemical analyses indicate that the ribonucleic acid
      (RNA) component of ribosomes is both necessary and sufficient for this
      stimulation.

PMID- 16963841
TI  - Stage 5 retinopathy of prematurity: then and now.

PMID- 16963842
TI  - Anatomical success rate after primary three-port lens-sparing vitrectomy in stage
      5 retinopathy of prematurity.
AB  - PURPOSE: To assess the anatomical success rate after three-port lens-sparing
      vitrectomy (LSV) in stage 5 (total) retinal detachments secondary to retinopathy
      of prematurity. METHODS: In a retrospective, interventional, single-surgeon,
      consecutive case series, the records of 33 eyes of 21 patients presenting with
      stage 5 retinal detachment secondary to retinopathy of prematurity who underwent
      primary three-port LSV from February 1998 to January 2004 were evaluated. Twenty
      one eyes (63.6%) had open anteriorly-open posteriorly and 12 (36.4%) had open
      anteriorly-narrow posteriorly in terms of anatomical configuration. The main
      outcome measure, retinal reattachment, was reviewed at final follow-up visits,
      which ranged from 6 months to 48 months (mean, 32 months) after LSV. RESULTS:
      Fifteen eyes (45.5%) maintained attachment and 18 eyes (54.5%) remained detached
      at the final visit. Open anteriorly-open posteriorly configuration eyes had a
      statistically significant higher anatomical success rate than eyes with an open
      anteriorly-narrow posteriorly configuration (P<0.001). CONCLUSIONS: Three-port
      LSV may achieve anatomical success in stage 5 retinopathy of prematurity-related
      detachments. The open anteriorly-open posteriorly configuration portends a better
      prognosis; thus, surgery should be performed before closure of the posterior
      retina into a funnel configuration, if possible.

PMID- 16963843
TI  - Anatomical and visual results of vitreoretinal surgery for stage 5 retinopathy of
      prematurity.
AB  - PURPOSE: To provide a historical perspective on outcomes of surgery for infants
      with stage 5 retinopathy of prematurity (ROP) as performed by a single surgeon
      over a 24-year period. DESIGN: Retrospective observational cohort study. METHODS:
      SETTING: Clinical practice of the Charles Retina Institute. PATIENTS: The 601
      infants with stage 5 ROP in at least one eye who were referred for surgery
      between 1977 and 2001. Charts were reviewed for demographic data and
      postoperative anatomical and visual acuity outcomes in eyes that underwent
      surgery. MAIN OUTCOME MEASURES: The postoperative anatomical status of the retina
      and visual function were assessed after surgery. Anatomical outcome was
      categorized as success (macula attached), partial success (macula detached),
      failure (total retinal detachment), or lost eye (opaque cornea, secluded pupil,
      or phthisis). Visual function was classified as>20/200, 20/200-5/200, hand
      movement, light perception, or no light perception. Multivariable logistic
      regression was used to explore relationships between outcomes and baseline
      characteristics. RESULTS: Only a minority of eyes had prior cryotherapy (15%) or
      laser photocoagulation (7%) therapy. The mean follow-up was 44 months for the 956
      eyes treated surgically. The 608 eyes with available follow-up data were
      classified as follows: 28% success, 5% partial success, 55% failure, and 11% lost
      eye. Visual function of light perception or better was achieved in 74% of the 183
      eyes with data on visual acuity. Controlling for other baseline factors, early
      postpartum age at the time of surgery was a statistically significant predictor
      of failure/lost eye (OR=2.08, 95% CI 1.09-3.97) and no light perception (OR=5.13,
      95% CI 1.45-18.14). Surgery for stage 5 ROP on the fellow eye was also a
      predictor of failure/lost eye (OR=2.38, 95% CI 1.39-4.08). CONCLUSIONS: Surgery
      resulted in anatomical success for approximately one third of infant eyes with
      stage 5 ROP, and only a minority of eyes (8 of 183) achieved visual acuity better
      than 5/200. However, some initially successfully attached retinas redetached.
      Although this study is limited by follow-up and may represent a group of patients
      with a more vascularly active disease state due to the low proportion of patients
      with prior peripheral ablation, this cohort of infants provides results against
      which future interventions may be compared.

PMID- 16963844
TI  - Lensectomy and vitrectomy with and without intravitreal triamcinolone acetonide
      for vascularly active stage 5 retinal detachments in retinopathy of prematurity.
AB  - PURPOSE: To determine the anatomical success rate of lensectomy and vitrectomy
      with and without intravitreal triamcinolone acetonide (TA) for vascularly active
      stage 5 tractional retinal detachments due to retinopathy of prematurity (ROP).
      METHODS: In a retrospective, interventional, single-surgeon, consecutive case
      series, the records of 21 eyes of 21 patients presenting with stage 5 retinal
      detachment secondary to ROP who underwent primary pars plicata vitrectomy with
      lensectomy from February 1998 to January 2004 were evaluated. All eyes were
      vascularly active at the time of surgery. Eleven eyes underwent the surgical
      procedure without TA (group 1), and 10 eyes received TA at the end of the
      procedure (group 2). The main outcome measure, retinal reattachment, was reviewed
      at the final follow-up visit, which ranged from 6 months to 42 months (mean, 28
      months) after surgery. RESULTS: None (0/11) of the eyes in group 1 maintained
      attachment, while 6 (60%) of 10 eyes in group 2 maintained at least posterior
      pole reattachment at the final visit. None of the group 2 eyes exhibited plus
      disease during follow-up. None of the eyes in either group exhibited signs of
      increased intraocular pressure after surgery. All six eyes that maintained
      posterior pole reattachment were able to fix and follow light at the last follow
      up visit. CONCLUSIONS: Vascularly active stage 5 ROP detachments portend a poor
      progress. The use of TA as a postoperative adjunct may improve the likelihood of
      retinal reattachment in select cases.

PMID- 16963845
TI  - Use of dorzolamide for patients with X-linked retinoschisis.
AB  - PURPOSE: To determine the value of a topical carbonic anhydrase inhibitor for the
      treatment of foveal lesions in patients with X-linked retinoschisis (XLRS).
      METHODS: Eight patients with XLRS and foveal cystic-appearing spaces by fundus
      examination and by optical coherence tomography (OCT) were treated with a topical
      form of carbonic anhydrase inhibitor. Changes in "foveal thickness" and "foveal
      zone thickness" were measured by OCT, and changes of best-corrected visual acuity
      were measured by Early Treatment Diabetic Retinopathy Study (ETDRS) charts.
      RESULTS: Seven of eight patients treated with 2% dorzolamide had a noticeable
      reduction in foveal thickness as well as cystic-appearing spaces by OCT. This
      reduction was found in both eyes in four of these patients and in one eye in one
      patient after 1 month of treatment. After an additional 1 month to 2 months of
      the same treatment regimen, two additional patients also had a noticeable
      reduction in foveal thickness as well as cystic-appearing spaces. Of these seven
      patients who had an improvement shown by OCT with treatment, five also had
      improvement of their visual acuity by >or=7 letters in at least one eye on ETDRS
      charts. CONCLUSION: The present study shows the efficacy of topical dorzolamide
      for treating foveal cystic-appearing lesions in patients with XLRS.

PMID- 16963846
TI  - Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization
      secondary to pathologic myopia: long-term study.
AB  - PURPOSE: To assess the safety and effectiveness of photodynamic therapy (PDT)
      with verteporfin for subfoveal choroidal neovascularization (CNV) secondary to
      pathologic myopia (PM). METHODS: Sixty-two patients (62 eyes) with PM underwent
      PDT according to the guidelines of the Verteporfin in Photodynamic Therapy Study.
      Clinical evaluations performed at all study visits included measurement of best
      corrected Snellen visual acuity, slit-lamp biomicroscopy, and fundus fluorescein
      angiography. Patients were followed up at 1 month and 3 months after treatment
      and thereafter at 3-month intervals. RESULTS: The final visual acuity of the
      study patients, after a median follow-up of 31 months, improved by >or=1 Snellen
      lines in 8 patients (13%), deteriorated in 20 (32%), and remained stable in 34
      (55%). The baseline visual acuity was similar in the various study groups. The
      final mean visual acuity in group A (55 years of age or younger) was 20/80 and
      significantly (P=0.006) better than that (20/138) in group B (older than 55 years
      of age). The mean final visual acuity in eyes with higher refractive error at
      baseline (greater than -17 diopters) was significantly better (P=0.014) than that
      in eyes with lower refractive error (-6 to -10 diopters). CNV size did not affect
      visual outcomes. CONCLUSION: PDT preserves vision in patients with CNV associated
      with PM. Younger patients and eyes with higher refractive error appear more
      likely to benefit from PDT with verteporfin.

PMID- 16963847
TI  - Optical coherence tomography after photodynamic therapy for patients with
      pathologic myopia.
AB  - PURPOSE: To evaluate early changes after photodynamic therapy (PDT) for patients
      with subfoveal choroidal neovascularization (CNV) due to pathologic myopia by
      optical coherence tomography (OCT). METHODS: PDT was performed on 10 eyes of 10
      patients who presented with subfoveal CNV due to pathologic myopia. OCT was used
      to evaluate changes 1 day, 3 days, and 7 days after therapy. Changes in
      intraretinal and subretinal fluid and CNV were examined on the images obtained.
      The retinal elevation and the height of the neurosensory retinal detachment were
      calculated. From these two values, the thickness of the neurosensory retina was
      obtained. The thickness of the neurosensory retina was measured to ascertain the
      intraretinal fluid change, and the height of the neurosensory retinal detachment
      was measured to ascertain the subretinal fluid change. RESULTS: The mean
      pretherapy retinal elevation+/-SD increased from 211+/-28 microm to 230+/-39
      microm 1 day after PDT and decreased to 221+/-36 microm 3 days after therapy. At
      7 days after therapy, the mean retinal elevation+/-SD was 211+/-22 microm. The
      retinal elevation was due to a subretinal fluid accumulation, whereas the
      thickness of the neurosensory retina increased only to a minor extent (range, 0
      22 microm) and the foveal architecture remained unchanged. The mean pretherapy
      height+/-SD of the neurosensory retinal detachment was 6+/-11 microm. It was 18+/
      20 microm, 12+/-12 microm, and 3+/-6 microm 1 day, 3 days, and 7 days after
      therapy, respectively. No change in CNV was observed during follow-up.
      CONCLUSION: The results of our study indicate that the acute infiltration
      observed in patients with pathologic myopia after PDT occurs in the first day and
      regresses during the first week. Yet, it should be noted that, unlike in patients
      with age-related macular degeneration, the acute infiltration phase can be
      observed by OCT only to a limited extent.

PMID- 16963848
TI  - Twofold illumination photodynamic therapy scheme for subfoveal choroidal
      neovascularization in pathologic myopia: results from a randomized pilot study.
AB  - PURPOSE: To compare the short-term efficacy and safety of standard verteporfin
      photodynamic therapy (PDT) to modified PDT regimen using a twofold illumination
      scheme for treating choroidal neovascularization in pathologic myopia. METHODS:
      Randomized active-controlled clinical trial including 16 patients with subfoveal
      choroidal neovascularization caused by pathologic myopia and best-corrected
      visual acuity (BCVA) of 20/320 or better. Patients were randomly assigned (1:1)
      to standard PDT regimen (50 J/cm; n=8) or twofold illumination PDT scheme (50+50
      J/cm; n=8). Comprehensive ophthalmic evaluation including fluorescein angiography
      was performed at baseline and at weeks 1, 12+/-2, and 24+/-2 following treatment.
      At week 12 follow-up examination, an additional treatment session with either
      standard or modified PDT regimens (as assigned at baseline) was applied to areas
      of fluorescein leakage if present. Changes in BCVA, retreatment rate, and
      incidence of adverse events were evaluated. RESULTS: All patients completed the
      24-week study period. Baseline median BCVA was 20/100 and 20/100 for patients
      assigned to standard and modified PDT regimens, respectively. At week 24, median
      improvement in BCVA was significantly greater in patients submitted to twofold
      illumination PDT scheme (P=0.005; Mann-Whitney U test). Median change from
      baseline in BCVA (ETDRS lines) was +1.8 (P<0.05; Wilcoxon signed-rank test),
      +0.4, and +0.5 lines for patients submitted to standard PDT regimen, and +1.8
      (P<0.05; Wilcoxon signed-rank test), +1.9 (P<0.05; Wilcoxon signed-rank test),
      and +2.4 (P<0.05; Wilcoxon signed-rank test) lines for patients submitted to
      twofold illumination PDT scheme at week 1, 12, and 24 follow-up examinations,
      respectively. An additional PDT session was performed in 7/8 patients assigned to
      standard PDT regimen, and in 4/8 patients assigned to modified PDT (P=0.28;
      Fisher exact test). No PDT-related complications were observed. CONCLUSION:
      Although the number of patients and length of follow-up in this study was
      limited, a better visual outcome and diminished retreatment rate were observed in
      patients assigned to twofold illumination PDT scheme in comparison to those
      submitted to standard PDT regimen. Larger studies with longer follow-up to look
      at twofold illumination PDT scheme versus standard one to confirm our preliminary
      results are warranted.

PMID- 16963849
TI  - Focal laser ablation of retinal angiomatous proliferation.
AB  - PURPOSE: To evaluate the feasibility of focal laser ablation of retinal
      angiomatous proliferation (RAP) identified with clinical examination and high
      speed indocyanine green (ICG) imaging in patients with age-related macular
      degeneration. METHODS: In this retrospective, interventional case series, 16
      consecutive eyes of 15 patients with macular degeneration and leakage from a
      stage I or II RAP lesion were identified. RAP lesions were identified using
      clinical examination and high-speed ICG imaging. High-speed ICG imaging was used
      to identify the intraretinal component of the lesion. RAP lesions were treated
      with a 100- to 200-mum green or yellow wavelength laser spot that was applied to
      completely ablate the intraretinal component of the lesion. In eyes with stage II
      lesions, the subretinal component of the lesion was not treated. Early Treatment
      of Diabetic Retinopathy Study visual acuity, optical coherence tomography retinal
      thickness, angiographic leakage, and progression of the angiomatous process shown
      by ICG imaging were evaluated preoperatively and postoperatively. RESULTS:
      Sixteen eyes underwent successful ablation of the RAP lesions with an average of
      1.9 treatment sessions. At a mean follow-up of 15.5 months, 94% of eyes had
      stable or improved visual acuity. Only 6% of eyes had a loss of >or=3 lines of
      visual acuity. The average visual acuity at the last follow-up was 20/45 in the
      stage I lesion group and 20/160 in the stage II lesion group. Of the patients,
      87.5% had a reduction in retinal edema and subretinal fluid, with 69% of patients
      having complete resolution of retinal edema and subretinal fluid; 14% of patients
      had progression to retinal choroidal anastomoses. No treatment complications were
      encountered. CONCLUSION: Focal laser photocoagulation of RAP lesions appears to
      be feasible. This treatment appears to be a safe method of managing the leakage
      from RAP. Treatment of solely the intraretinal component of the lesion may be
      adequate to control leakage. Treatment may allow the angiomatous process to be
      arrested, resulting in stabilization of visual acuity. Visual acuity results
      appear to be better for patients with early stage lesions.

PMID- 16963850
TI  - Anecortave acetate treatment for retinal angiomatous proliferation: a pilot
      study.
AB  - PURPOSE: The purpose of this study was to evaluate anecortave acetate treatment
      of retinal angiomatous proliferation (RAP), a neovascular form of age-related
      macular degeneration, with specific regard to inhibition of neovascularization
      and maintenance of vision. METHODS: Thirty-four patients with RAP with any stage
      of neovascularization were randomized 1:1:1 for treatment with three different
      quantities (30 mg, 15 mg, 3 mg) of anecortave acetate sterile suspension for
      juxtascleral administration. Best-corrected visual acuity (Early Treatment
      Diabetic Retinopathy Study chart), intraocular pressure measurement,
      biomicroscopy, funduscopy, digital fluorescein, and indocyanine green angiography
      were recorded at baseline and at 3 months. A 6-month retreatment interval was
      established for this study with a follow-up of 12 months. In selected patients
      optical coherence tomography was performed. The outcomes were mean changes in
      visual acuity and lesion size at 1 year. RESULTS: The detachment of the
      neurosensory retina and retinal pigment epithelium improved in all eyes, but all
      neovascular lesions increased in size. Vision loss occurred in the majority of
      study eyes (22 out of 34 eyes, 64.7%) independent of the concentration
      administered. CONCLUSION: The results suggest that a posterior juxtascleral
      injection of anecortave acetate reduces capillary permeability in patients with
      RAP. However, in spite of improvement of the exudation there is a progression of
      neovascularization and a significant loss of vision in all these patients. Like
      other monotherapeutic methods used to treat this variant of neovascular age
      related macular degeneration, anecortave acetate alone does not appear to benefit
      these patients. Future studies should investigate a combination form of therapy.

PMID- 16963851
TI  - Anecortave acetate for the treatment of idiopathic perifoveal telangiectasia: a
      pilot study.
AB  - PURPOSE: To investigate the use of anecortave acetate, a new angiostatic
      cortisene, for the treatment of the leakage and/or neovascularization associated
      with idiopathic perifoveal telangiectasia (IPT) in an open label prospective
      pilot study. METHODS: Seven eyes of six patients were treated with posterior
      juxtascleral administration of anecortave acetate delivered adjacent to the
      macula using a specially designed curved cannula. A full clinical examination and
      fluorescein angiography were performed at baseline and at 3-month intervals. The
      primary efficacy outcome for this pilot study was the mean change in visual
      acuity (Early Treatment Diabetic Retinopathy Study) from baseline. RESULTS: The
      visual acuity remained unchanged in two eyes of two patients with
      nonproliferative disease after 24 months. The five eyes of four patients
      presenting with subretinal neovascularization, the proliferative stage of IPT,
      showed stabilization or improvement of lesion size, resolution of leakage, and
      stabilization of vision at last follow-up. CONCLUSION: The results of this study
      suggest that anecortave acetate may inhibit retinal and subretinal permeability
      as well as neovascular proliferation in patients with IPT. A larger study
      accordingly should be designed in the future to evaluate the effectiveness and
      treatment of IPT with this drug.

PMID- 16963852
TI  - Interferon alfa-2a: a new treatment option for long lasting refractory cystoid
      macular edema in uveitis? A pilot study.
AB  - PURPOSE: To perform a prospective pilot study to evaluate interferon alfa-2a (IFN
      alfa-2a) for the treatment of refractory cystoid macular edema (CME) in
      endogenous uveitis. METHODS: IFN alfa-2a was administered at an initial dose of 3
      or 6 million IU (depending on body weight) per day subcutaneously. Afterwards IFN
      alfa-2a was tapered slowly over 6 months and finally discontinued. If CME
      relapsed IFN alfa-2a was reinstituted and tapered slowly again to evaluate the
      lowest maintenance dose to keep remission. RESULTS: A total of 15 eyes of 8
      patients with refractory CME due to intermediate or posterior uveitis were
      included. Ineffective pretreatment consisted of systemic steroids and
      acetazolamide (all patients) and at least one additional immunosuppressant (6
      patients). Six of 8 patients (11 eyes) responded well to IFN alfa-2a and CME
      resolved completely during 6 months treatment. One patient was lost to follow-up
      after IFN alfa-2a was stopped. In 1 patient (1 eye) even 19 months after
      cessation of IFN alfa-2a no recurrence of CME occurred. In 4 patients (8 eyes)
      IFN alfa-2a had to be reinstituted because CME relapsed. All 4 patients responded
      again. During a mean follow-up period of 16.4 months since restart of therapy we
      succeeded in all 4 patients to taper IFN alfa-2a to maintenance doses between 1.5
      million IU every second and every sixth day without a recurrence of CME in any of
      the 8 eyes. CONCLUSION: IFN alfa-2a can be a treatment option for patients with
      otherwise treatment resistant uveitic CME.

PMID- 16963853
TI  - Autologous plasmin for pharmacologic vitreolysis prepared 1 hour before surgery.
AB  - PURPOSE: To evaluate the safety and efficacy of intravitreal injection of
      autologous plasmin enzyme (APE) in inducing a posterior vitreous detachment
      (PVD). APE was obtained by a modified method 1 hour before surgery. METHODS: APE
      was obtained by centrifugation of autologous whole blood from the patients 1 hour
      before surgery and by incubation with streptokinase. APE was injected in the
      vitreous cavity 20 minutes before surgery. This procedure was applied for 20
      patients who underwent vitrectomy for macular pucker, macular hole, and macular
      edema due to vitreoretinal traction. The status of PVD was graded
      intraoperatively. The plasmin concentration obtained by this method and the
      plasminogen titer of the plasma from each patient were compared. Activated
      partial thromboplastin time was controlled before surgery and 1, 6, 12, and 24
      hours after surgery to evaluate alteration of the coagulation due to systemic
      absorption of the plasmin. RESULTS: Preparation of APE was easy and took on
      average 45 minutes for all patients. A PVD with an evident Weiss ring was
      observed during surgery in 17 eyes (85%). The average plasmin activity was 0.26
      IU/0.2 mL activated plasma. The partial thromboplastin time did not show any
      alteration in any of the patients with respect to preoperative values.
      CONCLUSION: APE obtained by this method can lead to a PVD and facilitate the
      complete remotion of vitreous cortex. The intravitreal injection does not lead to
      alteration of systemic blood coagulation.

PMID- 16963854
TI  - Influence of clinical factors on blue-on-yellow perimetry for diabetic patients
      without retinopathy: comparison with white-on-white perimetry.
AB  - PURPOSE: To investigate the influence of clinical factors (duration of diabetes
      mellitus, fasting blood sugar level, fructosamine concentration, and hemoglobin
      A1c) on blue-on-yellow (B-on-Y) perimetry compared with white-on-white (W-on-W)
      perimetry for diabetics without retinopathy. METHODS: Both B-on-Y perimetry and W
      on-W perimetry were performed for 33 diabetics without retinopathy. Thirty-three
      subjects with healthy eyes served as age-matched controls. RESULTS: For both
      diabetic patients and controls, mean deviation (MD) and corrected pattern SD of
      perimetry showed no difference irrespective of B-on-Y or W-on-W perimetry. For
      diabetics, MD of B-on-Y perimetry decreased in proportion to the morbid period
      with diabetes mellitus, with the same being true with deterioration of the
      clinical factors. Multiple regression analysis disclosed no differences in MD of
      clinical factors for W-on-W perimetry, despite the duration of diabetes mellitus
      exerting a significant influence on MD of B-on-Y perimetry. CONCLUSION: Even at
      the premorbid stage of diabetic retinopathy, longer duration of diabetes mellitus
      and longer persistence of poorly controlled diabetes mellitus are associated with
      an insidious progress of dysfunction in the retinal blue cone system.

PMID- 16963855
TI  - The impact of auditory and haptic feedback on computer task performance in
      patients with age-related macular degeneration and control subjects with no known
      ocular disease.
AB  - PURPOSE: To determine the impact of auditory and haptic (tactile) feedback on
      computer task performance of patients with age-related macular degeneration (AMD)
      compared to controls. METHODS: Thirty patients with AMD and 29 similarly aged
      controls with no known ocular disease completed timed computer icon "drag and
      drop" tasks under all four possible conditions of presence or absence of auditory
      and haptic feedback in a two-factor repeated measures design. Patient recruitment
      was stratified by best eye acuity: 20/20-20/50; 20/60-20/100; <20/100. Controls
      had best eye acuity>or=20/30. Task completion time was quantified using final
      target highlight time (FTHT) and total trial time, measured in milliseconds.
      RESULTS: Mean+/-standard deviation (SD) FTHT with neither feedback type in the
      three patient and control groups was, respectively: 1,110+/-356, 1,682+/-1,069,
      1,763+/-831, 924+/-533. Auditory feedback improved performance [%FTHT decrease, p
      value] in all groups, respectively: 18%, P=0.018; 38%, P=0.054; 57%, P=0.001;
      19%, P=0.001. Haptic feedback improved performance in the worst acuity AMD group
      and controls: 46%, P=0.009; 17%, P=0.038. In the worst acuity AMD group, auditory
      and/or haptic feedback was associated with a 4-6 second mean (for each task)
      reduction in total trial time. CONCLUSION: Auditory and haptic feedback can
      substantially increase performance speed of computer "drag and drop" tasks for
      patients with AMD, particularly in those patients with the most compromised
      vision.

PMID- 16963856
TI  - Evaluation of the toxicity of subretinal triamcinolone acetonide in the rabbit.
AB  - PURPOSE: Subretinal triamcinolone acetonide (TCA) might be a useful adjuvant in
      the treatment of subretinal neovascularization. The purpose of this study was to
      test the toxicity of subretinal TCA in the rabbit eye. METHODS: Sixteen New
      Zealand rabbits were vitrectomized and injected with either decanted TCA solution
      or vehicle. The concentration of injected TCA was 2 mg, and the delivered volume
      was 10 microL. Rabbits were examined on days 1, 3, and 7 and then once a week up
      to 3 months after surgery. Optical coherence tomography was performed at months
      1, 2, and 3. After the last examination, which included electroretinography, the
      rabbits were killed, and the eyes were enucleated for histopathologic analysis.
      RESULTS: Subretinal TCA appeared as a white circumscribed deposit. As the drug
      disappeared, areas of hyperpigmentation were seen adjacent to the drug deposit.
      Electroretinography tracings were normal, indicating no widespread toxic effect.
      Histologic analysis revealed areas of absence and/or hyperpigmentation of the
      retinal pigment epithelium and damage to photoreceptors and the outer nuclear
      layer of the retina. CONCLUSION: Subretinal injection of TCA crystals can be
      toxic to the outer retina and retinal pigment epithelium. Whether the potential
      beneficial effect of such a high-dose steroid in limiting subretinal
      inflammation, angiogenesis, and proliferation outweighs toxicity can only be
      determined from a clinical trial.

PMID- 16963857
TI  - Diagnostic and therapeutic challenges.

PMID- 16963858
TI  - Crystalline retinopathy from nasal ingestion of methamphetamine.

PMID- 16963859
TI  - Modified laser-induced chorioretinal anastomosis for treatment of longstanding
      perfused central retinal vein occlusion.

PMID- 16963860
TI  - Mycobacterium abscessus endophthalmitis: treatment dilemma and review of the
      literature.

PMID- 16963861
TI  - Delayed extrusion of ganciclovir implant.

PMID- 16963862
TI  - Endophthalmitis after 25-gauge transconjunctival sutureless vitrectomy.

PMID- 16963863
TI  - Total exudative retinal detachment in coats disease: biochemical analysis of the
      subretinal exudate.

PMID- 16963864
TI  - Abnormal response of the retinal pigment epithelium to photodynamic therapy in a
      child.

PMID- 16963865
TI  - Removal of submacular exudates in a patient with coats disease: a case report.

PMID- 16963866
TI  - Regression of neovascular iris vessels by intravitreal injection of bevacizumab.

PMID- 16963867
TI  - Case of anterior uveitis after intravitreal injection of bevacizumab.

PMID- 16963868
TI  - Retinal hole as a complication of long-standing subretinal perfluorocarbon
      liquid.

PMID- 16963869
TI  - Memory snare for extraction of intraocular foreign bodies.

PMID- 16963871
TI  - Long-term tamponade of perfluorocarbon liquid (PCL).

PMID- 16963872
TI  - 11th European Symposium on Suicide and Suicidal Behaviour, Portoroz, Slovenia, 9
      12 September 2006. Abstracts.

PMID- 16964179
TI  - Multimodal therapy for urologic cancers.

PMID- 16964178
TI  - Abrogation of the CLK-2 checkpoint leads to tolerance to base-excision repair
      intermediates.
AB  - Incorporation of uracil during DNA synthesis is among the most common types of
      endogenously generated DNA damage. Depletion of Caenorhabditis elegans dUTPase by
      RNA interference allowed us to study the role of DNA damage response (DDR)
      pathways when responding to high levels of uracil in DNA. dUTPase depletion
      compromised development, caused embryonic lethality and led to activation of cell
      cycle arrest and apoptosis. These phenotypes manifested as a result of processing
      misincorporated uracil by the uracil-DNA glycosylase UNG-1. Strikingly,
      abrogation of the clk-2 checkpoint gene rescued lethality and developmental
      defects, and eliminated cell-cycle arrest and apoptosis after dUTPase depletion.
      These data show a genetic interaction between UNG-1 and activation of the CLK-2
      DDR pathway after uracil incorporation into DNA. Our results indicate that
      persistent repair intermediates and/or single-stranded DNA formed during repair
      of misincorporated uracil are tolerated in the absence of the CLK-2 checkpoint in
      C. elegans.

PMID- 16964181
TI  - The case against extended lymph-node dissection for prostate cancer.

PMID- 16964180
TI  - An extended pelvic lymph-node dissection should be performed in most patients if
      radical prostatectomy is truly indicated.

PMID- 16964182
TI  - Can PSA nadir predict prostate cancer outcomes following radiotherapy?

PMID- 16964183
TI  - Safety and durability of dextranomer injections for urinary incontinence.

PMID- 16964184
TI  - Does saturation biopsy improve prostate cancer detection?

PMID- 16964185
TI  - The role of hormone replacement therapy in healthy elderly men.

PMID- 16964186
TI  - A combination of intravesical BCG [corrected] and [corrected] electromotive
      mitomycin for high-risk superficial bladder cancer.

PMID- 16964188
TI  - Can preoperative administration of isosulfan blue improve outcomes of subinguinal
      varicocelectomy?

PMID- 16964187
TI  - Immediate versus deferred androgen-deprivation therapy for prostate cancer: the
      jury is still out.

PMID- 16964189
TI  - Treatment for renal cancer: are we beyond the cytokine era?
AB  - Cytokines have been the mainstay of treatment for metastatic renal cancer for the
      past 20 years. Response rates of patients treated with these agents are low, and
      toxicity is high, but there is evidence from large multicenter randomized trials
      that indicate that there are survival benefits with interferon-based
      immunotherapy. A large number of new small molecule inhibitors are emerging that
      have caused considerable interest in the oncology community. The evidence for
      benefit from these compounds is based on small studies, using progression-free
      survival as an end-point. New compounds may provide an improvement in survival
      for patients with metastatic renal cancer; however, any trial of these agents
      should be tested against established, standard cytokine therapy.

PMID- 16964190
TI  - The prognostic and staging value of lymph node dissection in the treatment of
      invasive bladder cancer.
AB  - Regional lymph node dissection (LND) at the time of radical cystectomy is an
      essential component of the surgical management of invasive bladder cancer and
      might provide diagnostic and therapeutic benefits for both node-negative and node
      positive patients. The benefits obtained in pathologically node-negative patients
      might result from more complete resection of undetected micrometastases or from a
      more meticulous surgical technique. Advanced nodal disease also seems to be
      amenable to thorough surgical resection in a subpopulation of patients with
      bladder cancer. Despite the growing body of evidence to support the role of a
      more extended LND, no guidelines regarding the optimal boundaries of LND have
      been established. An increased number of resected nodes and wider LND boundaries
      have been associated with improved local disease control and prolonged survival.
      Additionally, mapping series indicate that the common iliac and presacral nodal
      regions are more frequently involved with tumor metastases than previously
      recognized. Efforts to limit any unnecessary dissection in patients at low risk
      for metastases--a tailored approach--has been proposed, but remains unproven.
      From the available evidence, the most reliable diagnostic and therapeutic
      approach to LND includes the routine extended LND in all patients undergoing
      cystectomy with curative intent.

PMID- 16964191
TI  - Drug Insight: 5alpha-reductase inhibitors for the treatment of benign prostatic
      hyperplasia.
AB  - Benign prostatic hyperplasia (BPH) is a common problem among older men, which is
      characterized by an enlarged prostate, lower urinary tract symptoms, and
      decreased flow of urine. It is a progressive disease that can lead to
      complications such as acute urinary retention (AUR) or a need for BPH-related
      surgery in some men. Dihydrotestosterone is the primary androgen involved in both
      normal and abnormal prostate growth and 5alpha-reductase inhibitors (5ARIs)
      inhibit the conversion of testosterone to dihydrotestosterone. There are two
      5ARIs licensed for the treatment of BPH; dutasteride, which inhibits both type 1
      and type 2 isoenzymes of 5alpha reductase, and finasteride, which inhibits the
      type 2 isoenzyme. Both 5ARIs have been shown to decrease prostate volume, improve
      urinary flow and lower urinary tract symptoms and reduce the risk of AUR and BPH
      related surgery. The prevention of disease progression, by treating the
      underlying cause, and the alleviation of symptoms are important aims of BPH
      therapy. 5ARIs are the only currently available medical therapy that can reduce
      the risk of AUR and BPH-related surgery while providing long-term symptom
      control. This provides a mandate for their use in men with enlarged prostates
      (volume >or=30 ml), who are at increased risk of disease progression.

PMID- 16964193
TI  - Making the most of microarrays.

PMID- 16964192
TI  - Leiomyoma of the epididymis treated with partial epididymectomy.
AB  - BACKGROUND: A 56-year-old man presented to a urology clinic with a painless left
      testicular mass of unknown duration. On physical examination, a firm mass
      measuring 2 cm x 2 cm and involving the inferior portion of the left epididymis
      was found. The left testicle, right testicle, and right epididymis looked normal
      on examination. INVESTIGATIONS: Assessment of tumor-marker levels, ultrasound
      examination of the scrotum, Doppler ultrasound examination, surgical exploration,
      and histologic examination of frozen sections. DIAGNOSIS: Pure leiomyoma arising
      from the epididymis. MANAGEMENT: Complete excision of the mass with its
      contiguous epididymis, preserving the left testicle and rest of the epididymis.

PMID- 16964194
TI  - Can Europe accelerate out of trouble?

PMID- 16964196
TI  - New clinical trials policy at FDA.

PMID- 16964195
TI  - Companies eye slice of age-related macular degeneration market.

PMID- 16964197
TI  - Amgen's TPO mimic faces stiff competition.

PMID- 16964198
TI  - BioXell: an Italian biotech success story?

PMID- 16964200
TI  - Abe Abuchowski.

PMID- 16964201
TI  - Biotech R&D goes further afield.

PMID- 16964202
TI  - Systems biology, incorporated?

PMID- 16964203
TI  - Clinical trial data: to disclose or not to disclose?

PMID- 16964204
TI  - The dog as a cancer model.

PMID- 16964205
TI  - How to stay out of a BIND.

PMID- 16964206
TI  - GM sterile mosquitoes--a cautionary note.

PMID- 16964207
TI  - Sequencing errors or SNPs at splice-acceptor guanines in dbSNP?

PMID- 16964209
TI  - Data integration gets 'Sloppy'.

PMID- 16964210
TI  - Replacing cRNA targets with cDNA reduces microarray cross-hybridization.

PMID- 16964211
TI  - Why spurning food biotech has become a liability.

PMID- 16964212
TI  - The breeder's dilemma--yield or nutrition?

PMID- 16964213
TI  - The protection racket.

PMID- 16964214
TI  - Oversight of US genetic testing laboratories.

PMID- 16964216
TI  - Recent patent applications in tissue engineering.

PMID- 16964215
TI  - Evidence and anecdotes: an analysis of human gene patenting controversies.

PMID- 16964217
TI  - Artificial sperm and epigenetic reprogramming.

PMID- 16964218
TI  - The worm turns for antimicrobial discovery.

PMID- 16964219
TI  - The sweet side of biomarker discovery.

PMID- 16964221
TI  - Empowering microarrays in the regulatory setting.

PMID- 16964222
TI  - Impact of microarray data quality on genomic data submissions to the FDA.

PMID- 16964223
TI  - A framework for the use of genomics data at the EPA.

PMID- 16964224
TI  - Data quality in genomics and microarrays.

PMID- 16964225
TI  - Evaluation of DNA microarray results with quantitative gene expression platforms.
AB  - We have evaluated the performance characteristics of three quantitative gene
      expression technologies and correlated their expression measurements to those of
      five commercial microarray platforms, based on the MicroArray Quality Control
      (MAQC) data set. The limit of detection, assay range, precision, accuracy and
      fold-change correlations were assessed for 997 TaqMan Gene Expression Assays, 205
      Standardized RT (Sta)RT-PCR assays and 244 QuantiGene assays. TaqMan is a
      registered trademark of Roche Molecular Systems, Inc. We observed high
      correlation between quantitative gene expression values and microarray platform
      results and found few discordant measurements among all platforms. The main cause
      of variability was differences in probe sequence and thus target location. A
      second source of variability was the limited and variable sensitivity of the
      different microarray platforms for detecting weakly expressed genes, which
      affected interplatform and intersite reproducibility of differentially expressed
      genes. From this analysis, we conclude that the MAQC microarray data set has been
      validated by alternative quantitative gene expression platforms thus supporting
      the use of microarray platforms for the quantitative characterization of gene
      expression.

PMID- 16964226
TI  - Using RNA sample titrations to assess microarray platform performance and
      normalization techniques.
AB  - We have assessed the utility of RNA titration samples for evaluating microarray
      platform performance and the impact of different normalization methods on the
      results obtained. As part of the MicroArray Quality Control project, we
      investigated the performance of five commercial microarray platforms using two
      independent RNA samples and two titration mixtures of these samples. Focusing on
      12,091 genes common across all platforms, we determined the ability of each
      platform to detect the correct titration response across the samples. Global
      deviations from the response predicted by the titration ratios were observed.
      These differences could be explained by variations in relative amounts of
      messenger RNA as a fraction of total RNA between the two independent samples.
      Overall, both the qualitative and quantitative correspondence across platforms
      was high. In summary, titration samples may be regarded as a valuable tool, not
      only for assessing microarray platform performance and different analysis
      methods, but also for determining some underlying biological features of the
      samples.

PMID- 16964227
TI  - Evaluation of external RNA controls for the assessment of microarray performance.
AB  - External RNA controls (ERCs), although important for microarray assay performance
      assessment, have yet to be fully implemented in the research community. As part
      of the MicroArray Quality Control (MAQC) study, two types of ERCs were
      implemented and evaluated; one was added to the total RNA in the samples before
      amplification and labeling; the other was added to the copyRNAs (cRNAs) before
      hybridization. ERC concentration-response curves were used across multiple
      commercial microarray platforms to identify problematic assays and potential
      sources of variation in the analytical process. In addition, the behavior of
      different ERC types was investigated, resulting in several important
      observations, such as the sample-dependent attributes of performance and the
      potential of using these control RNAs in a combinatorial fashion. This
      multiplatform investigation of the behavior and utility of ERCs provides a basis
      for articulating specific recommendations for their future use in evaluating
      assay performance across multiple platforms.

PMID- 16964228
TI  - Performance comparison of one-color and two-color platforms within the MicroArray
      Quality Control (MAQC) project.
AB  - Microarray-based expression profiling experiments typically use either a one
      color or a two-color design to measure mRNA abundance. The validity of each
      approach has been amply demonstrated. Here we provide a simultaneous comparison
      of results from one- and two-color labeling designs, using two independent RNA
      samples from the Microarray Quality Control (MAQC) project, tested on each of
      three different microarray platforms. The data were evaluated in terms of
      reproducibility, specificity, sensitivity and accuracy to determine if the two
      approaches provide comparable results. For each of the three microarray platforms
      tested, the results show good agreement with high correlation coefficients and
      high concordance of differentially expressed gene lists within each platform.
      Cumulatively, these comparisons indicate that data quality is essentially
      equivalent between the one- and two-color approaches and strongly suggest that
      this variable need not be a primary factor in decisions regarding experimental
      microarray design.

PMID- 16964231
TI  - Retraction: Identification of genes that function in the TNF-alpha-mediated
      apoptotic pathway using randomized hybrid ribozyme libraries.

PMID- 16964236
TI  - Five attributes of a successful manager in a research organization.

PMID- 16964238
TI  - All-solid-state Z-scheme in CdS-Au-TiO2 three-component nanojunction system.
AB  - Natural photosynthesis, which achieves efficient solar energy conversion through
      the combined actions of many types of molecules ingeniously arranged in a
      nanospace, highlights the importance of a technique for site-selective coupling
      of different materials to realize artificial high-efficiency devices. In view of
      increasingly serious energy and environmental problems, semiconductor-based
      artificial photosynthetic systems consisting of isolated photochemical system 1
      (PS1), PS2 and the electron-transfer system have recently been developed.
      However, the direct coupling of the components is crucial for retarding back
      reactions to increase the reaction efficiency. Here, we report a simple technique
      for forming an anisotropic CdS-Au-TiO2 nanojunction, in which PS1(CdS), PS2(TiO2)
      and the electron-transfer system (Au) are spatially fixed. This three-component
      system exhibits a high photocatalytic activity, far exceeding those of the single
      and two-component systems, as a result of vectorial electron transfer driven by
      the two-step excitation of TiO2 and CdS.

PMID- 16964229
TI  - The MicroArray Quality Control (MAQC) project shows inter- and intraplatform
      reproducibility of gene expression measurements.
AB  - Over the last decade, the introduction of microarray technology has had a
      profound impact on gene expression research. The publication of studies with
      dissimilar or altogether contradictory results, obtained using different
      microarray platforms to analyze identical RNA samples, has raised concerns about
      the reliability of this technology. The MicroArray Quality Control (MAQC) project
      was initiated to address these concerns, as well as other performance and data
      analysis issues. Expression data on four titration pools from two distinct
      reference RNA samples were generated at multiple test sites using a variety of
      microarray-based and alternative technology platforms. Here we describe the
      experimental design and probe mapping efforts behind the MAQC project. We show
      intraplatform consistency across test sites as well as a high level of
      interplatform concordance in terms of genes identified as differentially
      expressed. This study provides a resource that represents an important first step
      toward establishing a framework for the use of microarrays in clinical and
      regulatory settings.

PMID- 16964239
TI  - Prevalence of off-target effects in Drosophila RNA interference screens.
AB  - RNA interference (RNAi) in both plants and animals is mediated by small RNAs of
      approximately 21-23 nucleotides in length for regulation of target gene
      expression at multiple levels through partial sequence complementarities.
      Combined with widespread genome sequencing, experimental use of RNAi has the
      potential to interrogate systematically all genes in a given organism with
      respect to a particular function. However, owing to a tolerance for mismatches
      and gaps in base-pairing with targets, small RNAs could have up to hundreds of
      potential target sequences in a genome, and some small RNAs in mammalian systems
      have been shown to affect the levels of many messenger RNAs besides their
      intended targets. The use of long double-stranded RNAs (dsRNAs) in Drosophila,
      where Dicer-mediated processing produces small RNAs inside cells, has been
      thought to reduce the probability of such 'off-target effects' (OTEs). Here we
      show, however, that OTEs mediated by short homology stretches within long dsRNAs
      are prevalent in Drosophila. We have performed a genome-wide RNAi screen for
      novel components of Wingless (Wg) signal transduction in Drosophila S2R + cells,
      and found few, if any, legitimate candidates. Rather, many of the top candidates
      exert their effects on Wg response through OTEs on known pathway components or
      through promiscuous OTEs produced by tandem trinucleotide repeats present in many
      dsRNAs and genes. Genes containing such repeats are over-represented in candidate
      lists from published screens, suggesting that they represent a common class of
      false positives. Our results suggest simple measures to improve the reliability
      of genome-wide RNAi screens in Drosophila and other organisms.

PMID- 16964240
TI  - Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery.
AB  - Protein ubiquitination is a common form of post-translational modification that
      regulates a broad spectrum of protein substrates in diverse cellular pathways.
      Through a three-enzyme (E1-E2-E3) cascade, the attachment of ubiquitin to
      proteins is catalysed by the E3 ubiquitin ligase, which is best represented by
      the superfamily of the cullin-RING complexes. Conserved from yeast to human, the
      DDB1-CUL4-ROC1 complex is a recently identified cullin-RING ubiquitin ligase,
      which regulates DNA repair, DNA replication and transcription, and can also be
      subverted by pathogenic viruses to benefit viral infection. Lacking a canonical
      SKP1-like cullin adaptor and a defined substrate recruitment module, how the DDB1
      CUL4-ROC1 E3 apparatus is assembled for ubiquitinating various substrates remains
      unclear. Here we present crystallographic analyses of the virally hijacked form
      of the human DDB1-CUL4A-ROC1 machinery, which show that DDB1 uses one beta
      propeller domain for cullin scaffold binding and a variably attached separate
      double-beta-propeller fold for substrate presentation. Through tandem-affinity
      purification of human DDB1 and CUL4A complexes followed by mass spectrometry
      analysis, we then identify a novel family of WD40-repeat proteins, which directly
      bind to the double-propeller fold of DDB1 and serve as the substrate-recruiting
      module of the E3. Together, our structural and proteomic results reveal the
      structural mechanisms and molecular logic underlying the assembly and versatility
      of a new family of cullin-RING E3 complexes.

PMID- 16964241
TI  - The neurodegenerative disease protein aprataxin resolves abortive DNA ligation
      intermediates.
AB  - Ataxia oculomotor apraxia-1 (AOA1) is a neurological disorder caused by mutations
      in the gene (APTX) encoding aprataxin. Aprataxin is a member of the histidine
      triad (HIT) family of nucleotide hydrolases and transferases, and inactivating
      mutations are largely confined to this HIT domain. Aprataxin associates with the
      DNA repair proteins XRCC1 and XRCC4, which are partners of DNA ligase III and
      ligase IV, respectively, suggestive of a role in DNA repair. Consistent with
      this, APTX-defective cell lines are sensitive to agents that cause single-strand
      breaks and exhibit an increased incidence of induced chromosomal aberrations. It
      is not, however, known whether aprataxin has a direct or indirect role in DNA
      repair, or what the physiological substrate of aprataxin might be. Here we show,
      using purified aprataxin protein and extracts derived from either APTX-defective
      chicken DT40 cells or Aptx-/- mouse primary neural cells, that aprataxin resolves
      abortive DNA ligation intermediates. Specifically, aprataxin catalyses the
      nucleophilic release of adenylate groups covalently linked to 5'-phosphate
      termini at single-strand nicks and gaps, resulting in the production of 5'
      phosphate termini that can be efficiently rejoined. These data indicate that
      neurological disorders associated with APTX mutations may be caused by the
      gradual accumulation of unrepaired DNA strand breaks resulting from abortive DNA
      ligation events.

PMID- 16964242
TI  - Genome sequence of the bioplastic-producing "Knallgas" bacterium Ralstonia
      eutropha H16.
AB  - The H(2)-oxidizing lithoautotrophic bacterium Ralstonia eutropha H16 is a
      metabolically versatile organism capable of subsisting, in the absence of organic
      growth substrates, on H(2) and CO(2) as its sole sources of energy and carbon. R.
      eutropha H16 first attracted biotechnological interest nearly 50 years ago with
      the realization that the organism's ability to produce and store large amounts of
      poly[R-(-)-3-hydroxybutyrate] and other polyesters could be harnessed to make
      biodegradable plastics. Here we report the complete genome sequence of the two
      chromosomes of R. eutropha H16. Together, chromosome 1 (4,052,032 base pairs
      (bp)) and chromosome 2 (2,912,490 bp) encode 6,116 putative genes. Analysis of
      the genome sequence offers the genetic basis for exploiting the biotechnological
      potential of this organism and provides insights into its remarkable metabolic
      versatility.

PMID- 16964243
TI  - A probability-based approach for high-throughput protein phosphorylation analysis
      and site localization.
AB  - Data analysis and interpretation remain major logistical challenges when
      attempting to identify large numbers of protein phosphorylation sites by
      nanoscale reverse-phase liquid chromatography/tandem mass spectrometry (LC-MS/MS)
      (Supplementary Figure 1 online). In this report we address challenges that are
      often only addressable by laborious manual validation, including data set error,
      data set sensitivity and phosphorylation site localization. We provide a large
      scale phosphorylation data set with a measured error rate as determined by the
      target-decoy approach, we demonstrate an approach to maximize data set
      sensitivity by efficiently distracting incorrect peptide spectral matches (PSMs),
      and we present a probability-based score, the Ascore, that measures the
      probability of correct phosphorylation site localization based on the presence
      and intensity of site-determining ions in MS/MS spectra. We applied our methods
      in a fully automated fashion to nocodazole-arrested HeLa cell lysate where we
      identified 1,761 nonredundant phosphorylation sites from 491 proteins with a
      peptide false-positive rate of 1.3%.

PMID- 16964244
TI  - A K+-selective cGMP-gated ion channel controls chemosensation of sperm.
AB  - Eggs attract sperm by chemical factors, a process called chemotaxis. Sperm from
      marine invertebrates use cGMP signalling to transduce incident chemoattractants
      into changes in the Ca2+ concentration in the flagellum, which control the
      swimming behaviour during chemotaxis. The signalling pathway downstream of the
      synthesis of cGMP by a guanylyl cyclase is ill-defined. In particular, the ion
      channels that are involved in Ca2+ influx and their mechanisms of gating are not
      known. Using rapid voltage-sensitive dyes and kinetic techniques, we record the
      voltage response that is evoked by the chemoattractant in sperm from the sea
      urchin Arbacia punctulata. We show that the chemoattractant evokes a brief
      hyperpolarization followed by a sustained depolarization. The hyperpolarization
      is caused by the opening of K+-selective cyclic-nucleotide-gated (CNG) channels
      in the flagellum. Ca2+ influx commences at the onset of recovery from
      hyperpolarization. The voltage threshold of Ca2+ entry indicates the involvement
      of low-voltage-activated Ca(v) channels. These results establish a model of
      chemosensory transduction in sperm whereby a cGMP-induced hyperpolarization opens
      Ca(v) channels by a 'recovery-from-inactivation' mechanism and unveil an
      evolutionary kinship between transduction mechanisms in sperm and photoreceptors.

PMID- 16964245
TI  - Meiotic regulation of the CDK activator RINGO/Speedy by ubiquitin-proteasome
      mediated processing and degradation.
AB  - Xenopus RINGO/Speedy (XRINGO) is a potent inducer of oocyte meiotic maturation
      that can directly activate Cdk1 and Cdk2. Here, we show that endogenous XRINGO
      protein accumulates transiently during meiosis I entry and then is downregulated.
      This tight regulation of XRINGO expression is the consequence of two
      interconnected mechanisms: processing and degradation. XRINGO processing involves
      recognition of at least three distinct phosphorylated recognition motifs by the
      SCF(betaTrCP) ubiquitin ligase, followed by proteasome-mediated limited
      degradation, resulting in an amino-terminal XRINGO fragment. XRINGO processing is
      directly stimulated by several kinases, including protein kinase A and glycogen
      synthase kinase-3beta, and may contribute to the maintenance of G2 arrest. On the
      other hand, XRINGO degradation after meiosis I is mediated by the ubiquitin
      ligase Siah-2, which probably requires phosphorylation of XRINGO on Ser 243 and
      may be important for the omission of S phase at the meiosis-I-meiosis-II
      transition in Xenopus oocytes.

PMID- 16964246
TI  - Anti-oncogenic role of the endoplasmic reticulum differentially activated by
      mutations in the MAPK pathway.
AB  - Dysfunction of the endoplasmic reticulum (ER) has been reported in a variety of
      human pathologies, including cancer. However, the contribution of the ER to the
      early stages of normal cell transformation is largely unknown. Using primary
      human melanocytes and biopsies of human naevi (moles), we show that the extent of
      ER stress induced by cellular oncogenes may define the mechanism of activation of
      premature senescence. Specifically, we found that oncogenic forms of HRAS
      (HRAS(G12V)) but not its downstream target BRAF (BRAF(V600E)), engaged a rapid
      cell-cycle arrest that was associated with massive vacuolization and expansion of
      the ER. However, neither p53, p16(INK4a) nor classical senescence markers--such
      as foci of heterochromatin or DNA damage--were able to account for the specific
      response of melanocytes to HRAS(G12V). Instead, HRAS(G12V)-driven senescence was
      mediated by the ER-associated unfolded protein response (UPR). The impact of HRAS
      on the UPR was selective, as it was poorly induced by activated NRAS (more
      frequently mutated in melanoma than HRAS). These results argue against premature
      senescence as a converging mechanism of response to activating oncogenes and
      support a direct role of the ER as a gatekeeper of tumour control.

PMID- 16964247
TI  - Modification of p53 with O-linked N-acetylglucosamine regulates p53 activity and
      stability.
AB  - Post-translational addition of O-linked N-acetylglucosamine (O-GlcNAc) to p53 is
      known to occur, but the site of O-GlcNAcylation and its effects on p53 are not
      understood. Here, we show that Ser 149 of p53 is O-GlcNAcylated and that this
      modification is associated with decreased phosphorylation of p53 at Thr 155,
      which is a site that is targeted by the COP9 signalosome, resulting in decreased
      p53 ubiquitination. Accordingly, O-GlcNAcylation at Ser 149 stabilizes p53 by
      blocking ubiquitin-dependent proteolysis. Our results indicate that the dynamic
      interplay between O-GlcNAc and O-phosphate modifications coordinately regulate
      p53 stability and activity.

PMID- 16964248
TI  - FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP.
AB  - FOXO (Forkhead box O) transcription factors are important regulators of cellular
      metabolism, cell-cycle progression and cell death. FOXO activity is regulated by
      multiple post-translational modifications, including phosphorylation, acetylation
      and polyubiquitination. Here, we show that FOXO becomes monoubiquitinated in
      response to increased cellular oxidative stress, resulting in its re-localization
      to the nucleus and an increase in its transcriptional activity. Deubiquitination
      of FOXO requires the deubiquitinating enzyme USP7/HAUSP (herpesvirus-associated
      ubiquitin-specific protease), which interacts with and deubiquitinates FOXO in
      response to oxidative stress. Oxidative stress-induced ubiquitination and
      deubiquitination by USP7 do not influence FOXO protein half-life. However, USP7
      does negatively regulate FOXO transcriptional activity towards endogenous
      promoters. Our results demonstrate a novel mechanism of FOXO regulation and
      indicate that USP7 has an important role in regulating FOXO-mediated stress
      responses.

PMID- 16964249
TI  - Emotional enhancement of memory via amygdala-driven facilitation of rhinal
      interactions.
AB  - Emotions generally facilitate memory, an effect mediated by the basolateral
      amygdala (BLA). To study the underlying mechanisms, we recorded BLA, perirhinal
      and entorhinal neurons during an appetitive trace-conditioning task. We focused
      on the rhinal cortices because they constitute the interface between the
      hippocampus, a mediator of memory consolidation, and the neocortex, the storage
      site of declarative memories. We found that, after unexpected rewards, BLA
      activity increased impulse transmission from perirhinal to entorhinal neurons and
      that this effect decayed as the association between conditioned stimuli and
      rewards was learned. At this late phase of learning, the BLA effect occurred when
      the animals were anticipating the reward. By enhancing the processing of sensory
      cues, the BLA-mediated facilitation of rhinal interactions may explain how the
      amygdala promotes memory formation in emotional conditions.

PMID- 16964250
TI  - Nonlinear, binocular interactions underlying flow field selectivity of a motion
      sensitive neuron.
AB  - Neurons in many species have large receptive fields that are selective for
      specific optic flow fields. Here, we studied the neural mechanisms underlying
      flow field selectivity in lobula plate tangential cells (LPTCs) of the blowfly.
      Among these cells, the H2 cell responds preferentially to visual stimuli
      approximating rotational optic flow. Through double recordings from H2 and many
      other LPTCs, we characterized a bidirectional commissural pathway that allows
      visual information to be shared between the hemispheres. This pathway is mediated
      by axo-axonal electrical coupling of H2 and the horizontal system equatorial
      (HSE) cell located in the opposite hemisphere. Using single-cell ablations, we
      found that this pathway is sufficient to allow H2 to amplify and attenuate
      dendritic input during binocular visual stimuli. This is accomplished through a
      modulation of H2's membrane potential by input from the contralateral HSE cell,
      which scales the firing rate of H2 during visual stimulation but is not
      sufficient to induce action potentials.

PMID- 16964251
TI  - Soluble adenylyl cyclase is required for netrin-1 signaling in nerve growth
      cones.
AB  - Growth cones at the tips of nascent and regenerating axons direct axon
      elongation. Netrin-1, a secreted molecule that promotes axon outgrowth and
      regulates axon pathfinding, elevates cyclic AMP (cAMP) levels in growth cones and
      regulates growth cone morphology and axonal outgrowth. These morphological
      effects depend on the intracellular levels of cAMP. However, the specific
      pathways that regulate cAMP levels in response to netrin-1 signaling are unclear.
      Here we show that 'soluble' adenylyl cyclase (sAC), an atypical calcium-regulated
      cAMP-generating enzyme previously implicated in sperm maturation, is expressed in
      developing rat axons and generates cAMP in response to netrin-1. Overexpression
      of sAC results in axonal outgrowth and growth cone elaboration, whereas
      inhibition of sAC blocks netrin-1-induced axon outgrowth and growth cone
      elaboration. Taken together, these results indicate that netrin-1 signals through
      sAC-generated cAMP, and identify a fundamental role for sAC in axonal
      development.

PMID- 16964252
TI  - Meninges control tangential migration of hem-derived Cajal-Retzius cells via
      CXCL12/CXCR4 signaling.
AB  - Cajal-Retzius cells are critical in the development of the cerebral cortex, but
      little is known about the mechanisms controlling their development. Three focal
      sources of Cajal-Retzius cells have been identified in mice-the cortical hem, the
      ventral pallium and the septum-from where they migrate tangentially to populate
      the cortical surface. Using a variety of tissue culture assays and in vivo
      manipulations, we demonstrate that the tangential migration of cortical hem
      derived Cajal-Retzius cells is controlled by the meninges. We show that the
      meningeal membranes are a necessary and sufficient substrate for the tangential
      migration of Cajal-Retzius cells. We also show that the chemokine CXCL12 secreted
      by the meninges enhances the dispersion of Cajal-Retzius cells along the cortical
      surface, while retaining them within the marginal zone in a CXCR4-dependent
      manner. Thus, the meningeal membranes are fundamental in the development of Cajal
      Retzius cells and, hence, in the normal development of the cerebral cortex.

PMID- 16964253
TI  - Focal adhesion kinase signaling at sites of integrin-mediated adhesion controls
      axon pathfinding.
AB  - Extracellular matrix (ECM) components regulate neurite outgrowth in tissue
      culture and in vivo. Live imaging of phosphotyrosine (PY) signals revealed that
      Xenopus laevis growth cones extending on permissive ECM substrata assemble
      adhesive point contacts containing enriched levels of tyrosine-phosphorylated
      proteins. Whereas focal adhesion kinase (FAK) signaling is dispensable for the
      assembly of focal adhesions in non-neuronal cells, FAK activity is required for
      the formation of growth cone point contacts. FAK-dependent point contacts promote
      rapid neurite outgrowth by stabilizing lamellipodial protrusions on permissive
      ECM substrata. Moreover, local FAK activity is required for ECM-dependent growth
      cone turning in vitro, suggesting that FAK may control axon pathfinding in vivo.
      Consistent with this possibility, proper growth and guidance of Rohon-Beard
      sensory neurons and spinal commissural interneurons requires FAK activity. These
      findings identify FAK as a key regulator of axon growth and guidance downstream
      of growth cone-ECM interactions.

PMID- 16964254
TI  - When sustained attention impairs perception.
AB  - Virtually all behavioral and neurophysiological studies have shown that sustained
      (endogenous, conceptually driven) attention enhances perception. But can this
      enhancement be held indefinitely? We assessed the time course of attention's
      effects on contrast sensitivity, reasoning that if attention does indeed boost
      stimulus strength, the strengthened representation could result in stronger
      adaptation over time. We found that attention initially enhances contrast
      sensitivity, but that over time sustained attention can actually impair
      sensitivity to an attended stimulus.

PMID- 16964255
TI  - Brain state and contrast sensitivity in the awake visual thalamus.
AB  - Neuronal responses to visual stimuli depend on both the nature of the stimulus
      and brain state. Here we examined the contrast sensitivity of visual thalamic
      neurons as awake rabbits shifted between alert and nonalert states. We found that
      despite a large increase in response gain with alertness, contrast sensitivity
      remained nearly constant. This accurate scaling might be achieved through a
      balanced increase in excitation and inhibition with alertness.

PMID- 16964256
TI  - Evidence of off-target effects associated with long dsRNAs in Drosophila
      melanogaster cell-based assays.
AB  - To evaluate the specificity of long dsRNAs used in high-throughput RNA
      interference (RNAi) screens performed at the Drosophila RNAi Screening Center
      (DRSC), we performed a global analysis of their activity in 30 genome-wide
      screens completed at our facility. Notably, our analysis predicts that dsRNAs
      containing > or = 19-nucleotide perfect matches identified in silico to
      unintended targets may contribute to a significant false positive error rate
      arising from off-target effects. We confirmed experimentally that such sequences
      in dsRNAs lead to false positives and to efficient knockdown of a cross
      hybridizing transcript, raising a cautionary note about interpreting results
      based on the use of a single dsRNA per gene. Although a full appreciation of all
      causes of false positive errors remains to be determined, we suggest simple
      guidelines to help ensure high-quality information from RNAi high-throughput
      screens.

PMID- 16964258
TI  - Structural insights into the Notch-modifying glycosyltransferase Fringe.
AB  - Fringe proteins are beta1,3-N-acetylglucosaminyltransferases that modify Notch
      receptors, altering their ligand-binding specificity to regulate Notch signaling
      in development. We present the crystal structure of mouse Manic Fringe bound to
      UDP and manganese. The structure reveals amino acid residues involved in
      recognition of donor substrates and catalysis, and a putative binding pocket for
      acceptor substrates. Mutations of several invariant residues in this pocket
      impair Fringe activity in vivo.

PMID- 16964259
TI  - Structure and TBP binding of the Mediator head subcomplex Med8-Med18-Med20.
AB  - The Mediator head module stimulates basal RNA polymerase II (Pol II)
      transcription and enables transcriptional regulation. Here we show that the head
      subunits Med8, Med18 and Med20 form a subcomplex (Med8/18/20) with two
      submodules. The highly conserved N-terminal domain of Med8 forms one submodule
      that binds the TATA box-binding protein (TBP) in vitro and is essential in vivo.
      The second submodule consists of the C-terminal region of Med8 (Med8C), Med18 and
      Med20. X-ray analysis of this submodule reveals that Med18 and Med20 form related
      beta-barrel folds. A conserved putative protein-interaction face on the
      Med8C/18/20 submodule includes sites altered by srb mutations, which counteract
      defects resulting from Pol II truncation. Our results and published data support
      a positive role of the Med8/18/20 subcomplex in initiation-complex formation and
      suggest that the Mediator head contains a multipartite TBP-binding site that can
      be modulated by transcriptional activators.

PMID- 16964257
TI  - Fatal outcome of human influenza A (H5N1) is associated with high viral load and
      hypercytokinemia.
AB  - Avian influenza A (H5N1) viruses cause severe disease in humans, but the basis
      for their virulence remains unclear. In vitro and animal studies indicate that
      high and disseminated viral replication is important for disease pathogenesis.
      Laboratory experiments suggest that virus-induced cytokine dysregulation may
      contribute to disease severity. To assess the relevance of these findings for
      human disease, we performed virological and immunological studies in 18
      individuals with H5N1 and 8 individuals infected with human influenza virus
      subtypes. Influenza H5N1 infection in humans is characterized by high pharyngeal
      virus loads and frequent detection of viral RNA in rectum and blood. Viral RNA in
      blood was present only in fatal H5N1 cases and was associated with higher
      pharyngeal viral loads. We observed low peripheral blood T-lymphocyte counts and
      high chemokine and cytokine levels in H5N1-infected individuals, particularly in
      those who died, and these correlated with pharyngeal viral loads. Genetic
      characterization of H5N1 viruses revealed mutations in the viral polymerase
      complex associated with mammalian adaptation and virulence. Our observations
      indicate that high viral load, and the resulting intense inflammatory responses,
      are central to influenza H5N1 pathogenesis. The focus of clinical management
      should be on preventing this intense cytokine response, by early diagnosis and
      effective antiviral treatment.

PMID- 16964260
TI  - CDK Pho85 targets CDK inhibitor Sic1 to relieve yeast G1 checkpoint arrest after
      DNA damage.
AB  - In budding yeast, DNA damage in G1 activates a Rad9-dependent checkpoint that
      targets the cyclin-dependent kinase (CDK) Cdc28 to delay G1 exit. After a
      transient arrest, cells may enter S phase before completing DNA repair. We used
      genetic analysis to identify the stress-responsive CDK Pho85, the cyclin Pho80
      and the targeted transcription factors Pho4 and Swi5 as determinants of G1
      checkpoint adaptation. Consistent with opposing roles for the Cdc28 inhibitor
      Sic1 in blocking G1 exit and Pho85 in targeting Sic1 for proteolysis, mutation of
      Sic1 curtails G1 checkpoint delay, whereas Pho85 inhibition after DNA damage
      promotes Sic1 stability. G1 checkpoint delay in mutants lacking both Sic1 and
      Pho4 is independent of Pho85 activity. These data establish a G1 checkpoint
      adaptation pathway where Pho85 mediates Pho4 downregulation and Sic1 degradation
      to release Cdc28 activity and promote onset of S phase.

PMID- 16964261
TI  - Surface-bound chemokines capture and prime T cells for synapse formation.
AB  - T cell activation in vivo occurs in a lymphoid milieu that presents chemotactic
      and T cell receptor signals concurrently. Here we demonstrate that T cell zone
      chemokines such as CCL21 are bound to the surface of lymph node dendritic cells.
      Contact with antigen-presenting cells bearing chemokines costimulated T cells by
      a previously unknown two-step contact mechanism. T cells initially formed an
      antigen-independent 'tethered' adhesion on chemokine-bearing antigen-presenting
      cells. The formation of those tethers superseded T cell receptor signaling and
      immunological synapse formation. However, chemokine-tethered T cells were hyper
      responsive to subsequent contacts with antigen-presenting cells. Thus, T cells
      are costimulated 'in trans' and sequentially after initial engagement with their
      chemokine-rich environment.

PMID- 16964262
TI  - The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll
      like receptor signaling.
AB  - Toll-like receptors discriminate between different pathogen-associated molecules
      and activate signaling cascades that lead to immune responses. The specificity of
      Toll-like receptor signaling occurs by means of adaptor proteins containing Toll
      interleukin 1 receptor (TIR) domains. Activating functions have been assigned to
      four TIR adaptors: MyD88, Mal, TRIF and TRAM. Here we characterize a fifth TIR
      adaptor, SARM, as a negative regulator of TRIF-dependent Toll-like receptor
      signaling. Expression of SARM blocked gene induction 'downstream' of TRIF but not
      of MyD88. SARM associated with TRIF, and 'knockdown' of endogenous SARM
      expression by interfering RNA led to enhanced TRIF-dependent cytokine and
      chemokine induction. Thus, the fifth mammalian TIR adaptor SARM is a negative
      regulator of Toll-like receptor signaling.

PMID- 16964263
TI  - Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding
      a lysosomal type 5 P-type ATPase.
AB  - Neurodegenerative disorders such as Parkinson and Alzheimer disease cause motor
      and cognitive dysfunction and belong to a heterogeneous group of common and
      disabling disorders. Although the complex molecular pathophysiology of
      neurodegeneration is largely unknown, major advances have been achieved by
      elucidating the genetic defects underlying mendelian forms of these diseases.
      This has led to the discovery of common pathophysiological pathways such as
      enhanced oxidative stress, protein misfolding and aggregation and dysfunction of
      the ubiquitin-proteasome system. Here, we describe loss-of-function mutations in
      a previously uncharacterized, predominantly neuronal P-type ATPase gene, ATP13A2,
      underlying an autosomal recessive form of early-onset parkinsonism with pyramidal
      degeneration and dementia (PARK9, Kufor-Rakeb syndrome). Whereas the wild-type
      protein was located in the lysosome of transiently transfected cells, the
      unstable truncated mutants were retained in the endoplasmic reticulum and
      degraded by the proteasome. Our findings link a class of proteins with unknown
      function and substrate specificity to the protein networks implicated in
      neurodegeneration and parkinsonism.

PMID- 16964264
TI  - iASPP preferentially binds p53 proline-rich region and modulates apoptotic
      function of codon 72-polymorphic p53.
AB  - iASPP is one of the most evolutionarily conserved inhibitors of p53, whereas
      ASPP1 and ASPP2 are activators of p53. We show here that, in addition to the DNA
      binding domain, the ASPP family members also bind to the proline-rich region of
      p53, which contains the most common p53 polymorphism at codon 72. Furthermore,
      the ASPP family members, particularly iASPP, bind to and regulate the activity of
      p53Pro72 more efficiently than that of p53Arg72. Hence, escape from negative
      regulation by iASPP is a newly identified mechanism by which p53Arg72 activates
      apoptosis more efficiently than p53Pro72.

PMID- 16964265
TI  - Nucleosome positions predicted through comparative genomics.
AB  - DNA sequence has long been recognized as an important contributor to nucleosome
      positioning, which has the potential to regulate access to genes. The extent to
      which the nucleosomal architecture at promoters is delineated by the underlying
      sequence is now being worked out. Here we use comparative genomics to report a
      genome-wide map of nucleosome positioning sequences (NPSs) located in the
      vicinity of all Saccharomyces cerevisiae genes. We find that the underlying DNA
      sequence provides a very good predictor of nucleosome locations that have been
      experimentally mapped to a small fraction of the genome. Notably, distinct
      classes of genes possess characteristic arrangements of NPSs that may be
      important for their regulation. In particular, genes that have a relatively
      compact NPS arrangement over the promoter region tend to have a TATA box buried
      in an NPS and tend to be highly regulated by chromatin modifying and remodeling
      factors.

PMID- 16964266
TI  - Wnk4 controls blood pressure and potassium homeostasis via regulation of mass and
      activity of the distal convoluted tubule.
AB  - The mechanisms that govern homeostasis of complex systems have been elusive but
      can be illuminated by mutations that disrupt system behavior. Mutations in the
      gene encoding the kinase WNK4 cause pseudohypoaldosteronism type II (PHAII), a
      syndrome featuring hypertension and hyperkalemia. We show that physiology in mice
      transgenic for genomic segments harboring wild-type (TgWnk4(WT)) or PHAII mutant
      (TgWnk4(PHAII)) Wnk4 is changed in opposite directions: TgWnk4(PHAII) mice have
      higher blood pressure, hyperkalemia, hypercalciuria and marked hyperplasia of the
      distal convoluted tubule (DCT), whereas the opposite is true in TgWnk4(WT) mice.
      Genetic deficiency for the Na-Cl cotransporter of the DCT (NCC) reverses
      phenotypes seen in TgWnk4(PHAII) mice, demonstrating that the effects of the
      PHAII mutation are due to altered NCC activity. These findings establish that
      Wnk4 is a molecular switch that regulates the balance between NaCl reabsorption
      and K+ secretion by altering the mass and function of the DCT through its effect
      on NCC.

PMID- 16964267
TI  - Lack of effect of donor-recipient ABO mismatching on outcome following allogeneic
      hematopoietic stem cell transplantation.
AB  - Several recently published studies have suggested that patients who undergo ABO
      mismatched hematopoietic stem cell transplantation may be at increased risk for
      relapse, graft-versus-host disease, transplant-related mortality, and/or all
      cause mortality. To investigate this issue further, we analyzed potential
      associations between the donor-recipient ABO mismatch pattern and the above
      outcome measures among 240 consecutive patients who underwent allogeneic
      hematopoietic stem cell transplantation at our institution. Our analyses
      uncovered no significant associations between donor-recipient ABO mismatch
      pattern and overall survival, event-free survival, transplant-related mortality,
      incidence of acute graft-versus-host disease (GVHD), or incidence of chronic
      GVHD. Our data do not support recent assertions that donor-recipient ABO
      mismatching is a major risk factor for patients undergoing allogeneic transplant,
      nor do they support recent assertions that ABO matching should be an important
      consideration in selecting allogeneic hematopoietic stem cell donors.

PMID- 16964268
TI  - Bordetella pertussis respiratory infection following hematopoietic stem cell
      transplantation: time for universal vaccination?

PMID- 16964269
TI  - Poor oral nutrition after allogeneic stem cell transplantation correlates
      significantly with severe graft-versus-host disease.
AB  - It has previously been shown that enteral nutrition has several advantages
      compared to parenteral nutrition (PN) in critically ill patients. The nutritional
      history was studied in 231 patients after allogeneic stem cell transplantation
      (SCT). Parenteral nutrition was given for a median of 10 (0-74) days. Patients
      with graft-versus-host disease (GVHD) grades III-IV received more PN (median 20,
      range 0-67) than patients with GVHD grades 0-II (10, 0-74, P=0.016). Eighty-five
      (37%) patients were not able to eat anything for a median of 4 days (1-37). We
      found a correlation between the number of days with no oral intake (before the
      diagnosis of acute GVHD) and the incidence of acute GVHD grades III-IV. In
      patients with 1-4 days of no oral intake, the incidence of grades III-IV acute
      GVHD was 6%, in those with 5-9 days it was 17%, and in those with >9 days it was
      38%. On multivariate analysis, we found that more than 9 days with no oral intake
      was associated with acute GVHD grades III-IV (odds ratio 7.66, confidence
      interval 1.44-40.7, P=0.016). Poor oral intake early after SCT may be associated
      with an increased risk of developing severe acute GVHD.

PMID- 16964270
TI  - Methods for predicting bacterial protein subcellular localization.
AB  - The computational prediction of the subcellular localization of bacterial
      proteins is an important step in genome annotation and in the search for novel
      vaccine or drug targets. Since the 1991 release of PSORT I--the first
      comprehensive algorithm to predict bacterial protein localization--many other
      localization prediction tools have been developed. These methods offer
      significant improvements in predictive performance over PSORT I and the accuracy
      of some methods now rivals that of certain high-throughput laboratory methods for
      protein localization identification.

PMID- 16964271
TI  - Reverse-genetic approaches to the study of Borna disease virus.
AB  - Borna disease virus (BDV) is an enveloped virus that has a non-segmented,
      negative-strand RNA genome with the characteristic organization of the
      mononegaviruses. However, based on its unique genetic and biological features,
      BDV is considered to be the prototypic member of a new mononegavirus family, the
      Bornaviridae. BDV causes central nervous system (CNS) disease in a wide variety
      of mammals. This article discusses the recently developed reverse-genetics
      systems for BDV, and the implications for the elucidation of the molecular
      mechanisms underlying BDV-host interactions, including the basis of BDV
      persistence in the CNS and its associated diseases.

PMID- 16964272
TI  - GDC visitations--on their way out?

PMID- 16964273
TI  - Flexible learning: the future of postgraduate dental education.
AB  - Although mandatory CPD has long meant that dentists have had to keep their skills
      up to date, a growing number of GDPs are now also undertaking further
      postgraduate training such as diplomas and masters degrees. This article outlines
      the increasing range of options available to those wishing to develop their
      skills further.

PMID- 16964274
TI  - Undergraduate training as preparation for vocational training in England: a
      survey of vocational dental practitioners' and their trainers' views.
AB  - AIMS: To compare the views of new vocational dental practitioners (VDPs) and
      their trainers regarding how undergraduate dental education has prepared them for
      their vocational training (VT) in England. This study also aims to identify areas
      of relative weakness in dental undergraduate education that could influence the
      future training needs of vocational trainees. METHOD: Structured postal
      questionnaires were completed by VDPs and trainers from five Deaneries in
      England. The usable response rate was 71% (n = 186 VDPs and 186 trainers).
      RESULTS: The vast majority of VDPs and trainers perceived the undergraduate
      training in history taking, diagnosis and treatment planning for general practice
      to have been covered 'well' or even 'very well'. Undergraduate training in
      routine restorative dentistry, oral pathology and paediatric dentistry was also
      perceived to have been covered well. However, a large proportion of VDPs and
      trainers reported that they felt that undergraduate training in orthodontics,
      molar endodontics, surgical endodontics and surgical extraction of teeth had not
      adequately prepared them for VT. CONCLUSIONS: Newly qualified dentists appear to
      lack certain competencies recommended by the General Dental Council in The First
      Five Years. This has implications for dental undergraduate education, but also
      highlights current training needs during VT.

PMID- 16964275
TI  - The effectiveness of dental postgraduate courses--are we doing the right thing?
AB  - OBJECTIVE: To evaluate the effectiveness of dental postgraduate one-day courses
      in radiation protection in Wales. DESIGN: Analysis of dentists' performance pre-
      and immediately post-course training. SUBJECTS AND METHODS: Two hundred and
      eighty-five general dental practitioners took part in eight courses. Identical,
      validated multiple choice questionnaires were completed anonymously at the start
      and at the end of each course. Fifty (+62.5%) or above was regarded as a
      satisfactory standard. Two hundred and fifty-three (89%) paired morning-afternoon
      records were completed and analysed. Data was compared to that of similar courses
      five years earlier. RESULTS: The mean (SD) pre- and post-course percentage scores
      were 33.8 (13.5) and 63.6 (14.6). The mean improvement was 29.8 percentage points
      (SD 11.7). The pre-post correlation was +0.66. At baseline only six (2.4%) of the
      253 practitioners achieved the preset standard. After the course, 146 (57.7%) did
      so, an improvement of 55.3% (95% CI 48.9-61.3%). The final score and score gain
      were slightly higher in more recent graduates. The increase in proportion
      attaining the standard following training was 11.9% higher for IRMER than for
      POPUMET (p <0.001). CONCLUSION: The level of knowledge in radiation protection
      was very low at baseline. Whilst attending the approved course led to
      considerable improvement, it did not invariably result in a satisfactory level of
      knowledge in fundamental radiation physics and regulations. The prescribed
      standard was achieved by less than 60% of the attendees. The IRMER course was
      significantly more effective than its POPUMET predecessor.

PMID- 16964276
TI  - A randomised controlled trial of the effect of outreach placement on treatment
      planning by dental students.
AB  - Undergraduate dental students' curricula are being supplemented with primary care
      placements. OBJECTIVE: To compare the effect of outreach placement and
      traditional hospital-based training alone on students' treatment planning
      ability. DESIGN: Randomised controlled trial.Setting Four existing primary care
      placements in England during 2004. SUBJECTS AND METHODS: At follow-up the fourth
      year students took a history from a standard 'patient' then recorded a treatment
      plan. Interview skill was scored. The history and plan were assessed by
      clinicians blind to the intervention. INTERVENTION: Five-week block outreach
      placements for 25 of 49 students. MAIN OUTCOME MEASURES: Interviewing skill,
      quality of dental and social histories, the appropriateness of planned treatments
      and the consideration of wider issues. RESULTS: The two groups were similar in
      the scores for interviewing and taking a dental history. The outreach group
      scored higher for capturing a social history (outreach mean 4.4, SD = 2.1, n = 22
      and hospital 2.8, SD = 1.9, n = 23; p = 0.01) and for developing an appropriate
      treatment plan (5.6 [SD = 2.1] and 3.9 [SD = 2.3]; p = 0.01). There were no
      differences in scores relating to the wider issues. CONCLUSION: Dental outreach
      training was significantly more effective than traditional training alone in
      improving students' ability to capture relevant points of social history from a
      patient and to consider them when planning treatment.

PMID- 16964277
TI  - Progressing the action plan in Scotland--an educational perspective.
AB  - In March 2005 the Scottish Executive Health Department published the 'Action plan
      for improving oral health and modernising NHS dental services in Scotland'. Six
      areas required major new educational input: pre-qualification education,
      workforce supply, career development, dental practice and team development,
      clinical effectiveness/quality improvement and support for the oral health
      strategy. Targets from the action plan that have been fully achieved include: 1)
      undergraduate student numbers have reached the target output of 135 per year; 2)
      vocational training numbers match graduate numbers; 3) a vocational training
      scheme for dental therapists has been developed and numbers of VT places will
      match the number of qualifying therapists; 4) a new strategy to support dental
      nurse training will allow an additional 200 dental nurse training places by 2007;
      and 5) a clinical effectiveness programme has developed a rolling programme of
      guidelines, the first one of which, on conscious sedation, was released in May.
      The dental action plan has provided Scotland with the best opportunity for
      modernising dental services since the NHS was established. This paper describes
      some of the educational developments that will ensure NHS dental services in
      Scotland are 'fit for the future' and 'delivering for health'.

PMID- 16964278
TI  - Dentist apprentice.

PMID- 16964279
TI  - Normal cellular senescence and cancer susceptibility in mice genetically
      deficient in Ras-induced senescence-1 (Ris1).
AB  - Oncogenic Ras triggers a permanent cell-cycle arrest known as oncogene-induced
      senescence (OIS) that constitutes a relevant tumor suppressor mechanism. Ris1
      (Ras-induced senescence-1) is a novel gene that was identified in a screen as
      specifically upregulated during Ras-induced senescence, and that is located at a
      chromosomal region, 3p21.3, frequently lost in human cancer. Moreover, Ris1 is
      highly conserved in vertebrates, does not present paralogs, and its sequence does
      not reveal similarities with other proteins or domains. To analyse the
      physiological function of Ris1 and test its putative role as a tumor suppressor
      gene, we have generated mutant mice deficient for this gene. Ris1-null mice are
      viable, fertile, develop normally and do not display any obvious abnormalities.
      Of relevance, Ris1-deficient mice had a normal lifespan and did not exhibit
      predisposition to spontaneous tumors or to tumors induced by chemical
      carcinogens. Finally, Ris1-deficient embryonic fibroblasts were indistinguishable
      from wild-type cells regarding their proliferation properties, immortalization,
      senescence and oncogenic transformation. These findings do not support a role of
      Ris1 in tumor suppression or in OIS.

PMID- 16964280
TI  - WS5, a direct target of oncogenic transcription factor Myc, is related to human
      melanoma glycoprotein genes and has oncogenic potential.
AB  - We have isolated a gene (WS5) that is specifically expressed at the mRNA and
      protein level in avian fibroblasts transformed by the v-myc oncogene of avian
      acute leukemia virus MC29. In a conditional cell transformation system, WS5 gene
      expression was tightly correlated with v-myc activation. The WS5 gene contains 11
      exons, encoding a 733-amino acid protein with a transmembrane region and a
      polycystic kidney disease (PKD) domain. Near the transcriptional start site, the
      WS5 promoter contains a cluster of four binding sites for the Myc-Max complex and
      a binding site for transcription factor C/EBPalpha. Electrophoretic mobility
      shift assays and chromatin immunoprecipitation showed that Myc, Max and
      C/EBPalpha bind specifically to these sites. Functional promoter analyses
      revealed that both the Myc-binding site cluster and the C/EBPalpha-binding site
      are essential for strong transcriptional activation, and that Myc and C/EBPalpha
      synergistically activate the WS5 promoter. Ectopic expression of WS5 led to cell
      transformation documented by anchorage-independent growth. The human melanoma
      antigen Pmel17, a type I transmembrane glycoprotein, is the mammalian protein
      with the highest amino acid sequence identity (38%) to WS5. The Pmel17 gene is
      regulated by the MITF protein, a bHLHZip transcription factor with DNA binding
      specificities similar to those of Myc/Max. WS5 is also related to human
      glycoprotein GPNMB expressed in metastatic melanoma cells and implicated in the
      progression of brain and liver tumors.

PMID- 16964281
TI  - Ewing's sarcoma fusion protein, EWS/Fli-1 and Fli-1 protein induce PLD2 but not
      PLD1 gene expression by binding to an ETS domain of 5' promoter.
AB  - It was reported that short interfering RNA (siRNA) of EWS/Fli-1 downregulated
      phospholipase D (PLD)2 in Ewing's sarcoma (EWS) cell line, suggesting that PLD2
      is the target of aberrant transcription factor, EWS/Fli-1. Here, we further
      investigated the regulation of PLD2 gene expression by EWS/Fli-1 and Fli-1 in
      another EWS cell line, and also in EWS/Fli-1- or Fli-1-transfected cell line.
      EWS/Fli-1- or Fli-1-overexpressed cells showed higher PLD2 but not PLD1 protein
      expression and enhanced cell proliferation as compared to mock transfectant. The
      treatment of these cells with 1-butanol or siRNA of PLD2 inhibited cell growth,
      suggesting the pivotal role of PLD in cell growth promotion. PLD2 but not PLD1
      mRNA level was also increased in EWS/Fli-1 or Fli-1-transfectants. After
      determining the transcription initiation points, we cloned the 5' promoter of
      both PLD1 and PLD2 and analysed promoter activities. Results showed that EWS/Fli
      1 and Fli-1 increase PLD2 gene expression by binding to an erythroblast
      transformation-specific domain (-126 to -120 bp from the transcription initiation
      site) of PLD2 promoter, which is the minimal and most powerful region.
      Electrophoresis mobility shift assay using truncated proteins showed that both
      DNA-binding domain and trans-activating domain were necessary for the enhanced
      gene expression of PLD2.

PMID- 16964282
TI  - Genetic dissection of the role of p21Cip1/Waf1 in p53-mediated tumour
      suppression.
AB  - Protein p21Cip1/Waf1 is transcriptionally activated by the tumour suppressor p53
      and previous studies have shown that p21 plays a role in tumour suppression.
      However, the involvement of p21 in p53-mediated tumour suppression remains to be
      directly demonstrated in vivo. Tumour suppression mediated by p53 can be measured
      by comparing tumour susceptibility in animals carrying two (wild-type mice) or
      three (super-p53 mice) copies of the p53 gene. We have taken advantage of this
      genetically defined system to measure p53-mediated cell-cycle arrest, apoptosis
      and tumorigenesis, in a p21 wild-type and in a p21-null context. The absence of
      p21 significantly impaired the enhanced p53-mediated cell-cycle arrest
      characteristic of super-p53 cells, but did not affect the enhanced apoptosis.
      Importantly, in an experimental model of fibrosarcoma induction, the absence of
      p21 significantly decreased the tumour suppression benefit of super-p53 mice. We
      conclude that cell-cycle arrest through p21 plays a significant role in mediating
      p53-dependent cancer protection.

PMID- 16964283
TI  - RalA regulates vascular endothelial growth factor-C (VEGF-C) synthesis in
      prostate cancer cells during androgen ablation.
AB  - Prostate cancer mortality is primarily due to failure to cure patients with
      metastatic disease. In its early stages, prostate cancer growth is enhanced by
      androgens. As such, the primary therapy for advanced (locally extensive or
      metastatic) prostate cancer consists of androgen deprivation therapy by
      pharmacotherapeutic or surgical means. Eventually, the tumor recurs owing to a
      transition from androgen-dependence to a highly metastatic and androgen
      refractory (androgen depletion-independent) phenotype. As the detailed molecular
      mechanism underlying this transition to a more aggressive phenotype is poorly
      understood, it has been difficult to develop effective treatments for this
      advanced stage of the disease. We have previously reported an increase in
      vascular endothelial growth factor-C (VEGF-C) expression in human prostate cancer
      cells after androgen withdrawal. We have also shown increased expression of the
      androgen receptor co-activator BAG-1L by VEGF-C, suggesting the involvement of
      this growth factor in transactivation of the androgen receptor, even at low
      concentrations of androgen. In our present study, we show that androgen
      deprivation of human prostate carcinoma cells activates the small GTPase, RalA, a
      molecule important for human oncogenesis. RalA activation leads to VEGF-C
      upregulation. We also show that elevated levels of intracellular reactive oxygen
      species in prostate cancer cells under androgen-ablated conditions is the major
      inducer of RalA activation and VEGF-C synthesis.

PMID- 16964284
TI  - Prohibitin, a protein downregulated by androgens, represses androgen receptor
      activity.
AB  - Prohibitin (PHB) is a cell cycle regulatory protein, known to repress E2F1
      mediated gene activation via recruitment of transcriptional regulatory factors
      such as retinoblastoma and histone deacetylase 1 (HDAC1). We previously
      identified PHB as a target protein of androgen signaling in prostate cancer cells
      and showed that downregulation of PHB is required for androgen-induced cell cycle
      entry in these cells. We now present evidence that PHB, which has 54% homology at
      the protein level to the oestrogen receptor corepressor REA (repressor of
      oestrogen receptor activity), can repress androgen receptor (AR)-mediated
      transcription and androgen-dependent cell growth. Depletion of endogenous PHB
      resulted in an increase in expression of the androgen-regulated prostate-specific
      antigen gene. The repression appears to be specific to androgen and closely
      related receptors, as it is also evident for the glucocorticoid and progesterone,
      but not oestrogen, receptors. In spite of interaction of PHB with HDAC1, HDAC
      activity is not required for this repression. Although AR and PHB could be co
      immunoprecipitated, no direct interaction was detectable, suggesting that PHB
      forms part of a repressive complex with the AR. Competition with the co-activator
      SRC1 further suggests that formation of a complex with AR, PHB and other
      cofactors is the mechanism by which repression is achieved. It appears then that
      repression of AR activity is one mechanism by which PHB inhibits androgen
      dependent growth of prostate cells. Further, this study implies that the AR
      itself could, by mediating downregulation of a corepressor, be involved in the
      progression of prostate tumours to the hormone refractory stage.

PMID- 16964285
TI  - Mechanism of ASC-mediated apoptosis: bid-dependent apoptosis in type II cells.
AB  - Apoptosis-associated speck-like protein containing a CARD (ASC) is an adaptor
      molecule that mediates apoptotic and inflammatory signals, and implicated in
      tumor suppression. However, the mechanism of ASC-mediated apoptosis has not been
      well elucidated. Here, we investigated the molecular mechanisms of ASC-mediated
      apoptosis in several cell lines using a caspase recruitment domain 12-Nod2
      chimeric protein that transduces the signal from muramyl dipeptide into ASC
      mediated apoptosis. Experiments using dominant-negative mutants, small
      interfering RNAs and peptide inhibitors for caspases indicated that caspase-8 was
      generally required for ASC-mediated apoptosis, whereas a requirement for caspase
      9 depended on the cell type. In addition, caspase-like apoptosis-regulatory
      protein (CLARP)/Fas-like inhibitor protein, a natural caspase-8 inhibitor,
      suppressed ASC-mediated apoptosis, and Clarp-/- mouse embryonic fibroblasts were
      highly sensitive to ASC-mediated apoptosis. Bax-deficient HCT116 cells were
      resistant to ASC-mediated apoptosis as reported previously, although we failed to
      observe colocalization of ASC and Bax in cells. Like Fas-ligand-induced
      apoptosis, the ASC-mediated apoptosis was inhibited by Bcl-2 and/or Bcl-XL in
      type-II but not type-I cell lines. Bid was cleaved upon ASC activation, and
      suppression of endogenous Bid expression using small-interfering RNAs in type-II
      cells reduced the ASC-mediated apoptosis. These results indicate that ASC, like
      death receptors, mediates two types of apoptosis depending on the cell type, in a
      manner involving caspase-8.

PMID- 16964286
TI  - Transcriptional regulation of KiSS-1 gene expression in metastatic melanoma by
      specificity protein-1 and its coactivator DRIP-130.
AB  - Loss of the metastasis suppressor gene, KiSS-1 has been strongly correlated to
      the progression of metastases in numerous types of cancers. The mechanism through
      which KiSS-1 is lost during metastasis, however, is still not completely known.
      Previous studies have shown that genetic material on human chromosome 6q16.3-q23
      is essential for KiSS-1 expression in normal tissues. Additionally, microcell
      mediated transfer of this chromosome in cancerous tissue results in rescued
      expression of KiSS-1 and reduced metastatic phenotype. Here, we show that loss of
      Sp1-coactivator protein DRIP-130, which is encoded by human chromosome 6q16.3
      q23, results in reduced KiSS-1 promoter activation in highly malignant melanoma
      cells. Co-expression of Sp1 and DRIP-130 not only rescues KiSS-1 expression, but
      also induces an inhibition of the invasive and migratory behavior in highly
      metastatic melanoma cells, similar to the overexpression of KiSS-1 metastasis
      suppressor gene in those cells. Furthermore, we demonstrate that KiSS-1
      expression is regulated by Sp1 elements within the first 100-bp region of the
      KiSS-1 promoter and that targeted deletion of a single GC-rich region spanning 
      93 to -58 interrupts Sp1- and DRIP-130-modulated transcriptional control of KiSS
      1 expression. Our results thus suggest that DRIP-130 is a key regulator in KiSS-1
      transactivation in normal tissue, and that the loss of DRIP-130 expression, as a
      result of the gross loss of human chromosome 6q16.3-q23, provokes increased tumor
      metastasis.

PMID- 16964287
TI  - Involvement of protein phosphatase 2A nuclear accumulation and subsequent
      inactivation of activator protein-1 in leptomycin B-inhibited cyclin D1
      expression.
AB  - Leptomycin B (LMB) is a Streptomyces metabolite that causes the specific
      inhibition of the nuclear export of proteins containing a nuclear export signal
      (NES). LMB was reported to inhibit cell cycle progression in fission yeast and
      mammalian cells, however, the mechanism underlying LMB-induced cell cycle arrest
      is still obscure. In this study, we found that in serum-starved NIH3T3 cells, LMB
      inhibited serum-induced cyclin D1 expression at the level of transcription.
      However, this inhibition was reversed by inhibitors of protein phosphatase 2A
      (PP2A). Furthermore, we found that PP2A accumulated in the nucleus upon treatment
      with LMB. The finding prompted us to identify the functional NES in PP2A
      catalytic subunit alpha. These results indicated that LMB inhibited the
      chromosomal region maintenance 1 (CRM1)-dependent nuclear export of PP2A,
      resulting in sustained dephosphorylation in the nucleus. Although phosphorylation
      of c-Jun at Ser-63 is required for activator protein 1 (AP-1)-dependent
      expression of cyclin D1, it decreased in LMB-treated cells compared to untreated
      cells. Moreover, the inhibitors of PP2A restored the levels of c-Jun
      phosphorylated at Ser-63. We propose that inhibition of cyclin D1 expression by
      LMB is mediated by the LMB-induced nuclear accumulation of PP2A, leading to
      sustained dephosphorylation of c-Jun at Ser-63, which leads to inactivation of
      the transcription of the AP-1-responsive cyclin D1 gene.

PMID- 16964288
TI  - Characterizing a rat Brca2 knockout model.
AB  - Evidence exists that BRCA2 carriers may have an elevated risk of breast, ovarian,
      colon, prostate, and pancreatic cancer. In general, carriers are defined as
      individuals with protein truncating mutations within the BRCA2 gene. Many Brca2
      knockout lines have been produced and characterized in the mouse. We previously
      produced a rat Brca2 knockout strain in which there is a nonsense mutation in
      exon 11 between BRC repeats 2 and 3, and a truncated protein is produced.
      Interestingly, while such a mutation in homozygous mice would lead to limited
      survival of approximately 3 months, the Brca2-/- rats are 100% viable and the
      vast majority live to over 1 year of age. Brca2-/- rats show a phenotype of
      growth inhibition and sterility in both sexes. Aspermatogenesis in the Brca2-/-
      rats is due to a failure of homologous chromosome synapsis. Long-term phenotypes
      include underdeveloped mammary glands, cataract formation and lifespan shortening
      due to the development of tumors and cancers in multiple organs. The
      establishment of the rat Brca2 knockout model provides a means to study the role
      of Brca2 in increasing cancer susceptibility and inducing a novel ocular
      phenotype not previously associated with this gene.

PMID- 16964289
TI  - Identification of a new class of PAX3-FKHR target promoters: a role of the Pax3
      paired box DNA binding domain.
AB  - Alveolar rhabdomyosarcoma (aRMS), an aggressive skeletal muscle cancer, carries a
      unique t(2;13) chromosomal translocation resulting in the formation of a chimeric
      transcription factor PAX3-FKHR. This fusion protein contains the intact DNA
      binding domains (PD: paired box binding domain; HD: paired-type homeodomain) of
      Pax3 fused to the activation domain of FKHR. Cells expressing Pax3 and PAX3-FKHR
      show vastly different gene expression patterns, despite that they share the same
      DNA-binding domains. We present evidence of a gain of function mechanism that
      allows the fusion protein to recognize and transcriptionally activate response
      elements containing a PD-specific binding site. This DNA recognition specificity
      is in contrast to the requirement for Pax3-specific target sequences that must
      contain a composite of PD-and HD-binding sites. Domain swapping studies suggest
      that an increased structural flexibility could account for the relaxed DNA
      targeting specificity in PAX3-FKHR. Here, we identify myogenin gene as a direct
      target of PD-dependent PAX3-FKHR activation pathway in vitro and in vivo. We
      demonstrate that PAX3-FKHR could induce myogenin expression in undifferentiated
      myoblasts by a MyoD independent pathway, and that PAX3-FKHR is directly involved
      in myogenin expression in aRMS cells.

PMID- 16964290
TI  - Androgen regulation of soluble guanylyl cyclasealpha1 mediates prostate cancer
      cell proliferation.
AB  - The growth and progression of prostate cancer are dependent on androgens and
      androgen receptor (AR), which act by modulating gene expression. Utilizing a gene
      microarray approach, we have identified the alpha1-subunit gene of soluble
      guanylyl cyclase (sGC) as a novel androgen-regulated gene. A heterodimeric
      cytoplasmic protein composed of one alpha and one beta subunit, sGC mediates the
      widespread cellular effects of nitric oxide (NO). We report here that, in
      prostate cancer cells, androgens stimulate the expression of sGCalpha1. A cloned
      human sGCalpha1 promoter is activated by androgen in an AR-dependent manner,
      suggesting that sGCalpha1 may be a direct AR target gene. Disruption of sGCalpha1
      expression severely compromises the growth of both androgen-dependent and
      androgen-independent AR-positive prostate cancer cells. Overexpression of
      sGCalpha1 alone is sufficient for stimulating prostate cancer cell proliferation.
      Interestingly, the major growth effect of sGCalpha1 is independent of NO and
      cyclic guanosine monophosphate, a major mediator of the sGC enzyme. These data
      strongly suggest that sGCalpha1 acts in prostate cancer via a novel pathway that
      does not depend on sGCbeta1. Tissue studies show that sGCalpha1 expression is
      significantly elevated in advanced prostate cancer. Thus, sGCalpha1 may be an
      important mediator of the procarcinogenic effects of androgens.

PMID- 16964291
TI  - Parafibromin is a nuclear protein with a functional monopartite nuclear
      localization signal.
AB  - Parafibromin is a nuclear protein with a tumour suppressor role in the
      development of non-hereditary and hereditary parathyroid carcinomas, and the
      hyperparathyroidism-jaw tumour (HPT-JT) syndrome, which is associated with renal
      and uterine tumours. Nuclear localization signal(s), (NLS(s)), of the 61 kDa
      parafibromin remain to be defined. Utilization of computer-prediction programmes,
      identified five NLSs (three bipartite (BP) and two monopartite (MP)). To
      investigate their functionality, wild-type (WT) and mutant parafibromin
      constructs tagged with enhanced green fluorescent protein or cMyc were
      transiently expressed in COS-7 cells, or human embryonic kidney 293 (HEK293)
      cells, and their subcellular locations determined by confocal fluorescence
      microscopy. Western blot analyses of nuclear and cytoplasmic fractions from the
      transfected cells were also performed. WT parafibromin localized to the nucleus
      and deletions or mutations of the three predicted BP and one of the predicted MP
      NLSs did not affect this localization. In contrast, deletions or mutations of a
      MP NLS, at residues 136-139, resulted in loss of nuclear localization.
      Furthermore, the critical basic residues, KKXR, of this MP NLS were found to be
      evolutionarily conserved, and over 60% of all parafibromin mutations lead to a
      loss of this NLS. Thus, an important functional domain of parafibromin,
      consisting of an evolutionarily conserved MP NLS, has been identified.

PMID- 16964292
TI  - Genetic induction of tumorigenesis in swine.
AB  - The transition from basic to clinical cancer research for a number of
      experimental therapeutics is hampered by the lack of a genetically malleable,
      large animal model. To this end, we genetically engineered primary porcine cells
      to be tumorigenic by expression of proteins known to perturb pathways commonly
      corrupted in human cancer. Akin to human cells, these porcine cells were quite
      resistant to transformation, requiring multiple genetic changes. Moreover, the
      transformed porcine cells produced tumors when returned to the isogenic host
      animal. The ability to now rapidly and reproducibly genetically induce tumors of
      sizes similar to those treated clinically in a large mammal similar to humans in
      many respects will provide a robust cancer model for preclinical studies
      dependent on generating large tumors.

PMID- 16964294
TI  - Differential effects of inactivated Axin1 and activated beta-catenin mutations in
      human hepatocellular carcinomas.
AB  - Perturbations to the Wnt signaling pathway have been implicated in a large
      proportion of human hepatocellular carcinomas (HCCs). Activating beta-catenin
      mutations and loss of function mutations in Axin1 are thought to be functionally
      equivalent. We examined the Wnt pathway in HCC by comparing the expression of
      beta-catenin target genes and the level of beta-catenin-dependent transcriptional
      activation, in 45 HCC tumors and four cell lines. Among these samples, beta
      catenin and AXIN1 were mutated in 20 and seven cases, respectively. We found a
      significant correlation between activated beta-catenin mutations and
      overexpression of mRNA for the target genes glutamine synthetase (GS), G-protein
      coupled receptor (GPR)49 and glutamate transporter (GLT)-1 (P=0.0001), but not
      for the genes ornithine aminotransferase, LECT2, c-myc and cyclin D1. We also
      showed that GS is a good immunohistochemical marker of beta-catenin activation in
      HCC. However, we observed no induction of GS, GPR49 or GLT-1 in the five
      inactivated Axin1 tumors. Beta-catenin-dependent transcriptional activation in
      two Axin1-mutated HCC cell lines was much weaker than in beta-catenin-mutated
      cell lines. Our results strongly suggest that in HCC, contrary to expectation,
      the loss of function of Axin1 is not equivalent to the gain of function of beta
      catenin. Our results also suggest that the tumor suppressor function of Axin1 in
      HCC may be related to another, non-Wnt pathway.

PMID- 16964295
TI  - Erucism in New Zealand: exposure to gum leaf skeletoniser (Uraba lugens)
      caterpillars in the differential diagnosis of contact dermatitis in the Auckland
      region.
AB  - There are no indigenous caterpillars known to be associated with erucism, but the
      recently established gum leaf skeletoniser (Uraba lugens) has venom-containing
      spines that cause adverse reactions in humans. Symptoms are usually characterised
      by a stinging sensation, followed by itching and the formation of wheals.
      Exposure to U. lugens should be considered by medical practitioners in the
      differential diagnosis of contact dermatitis in the Auckland region.

PMID- 16964296
TI  - Vitamin D deficiency in pregnant New Zealand women.
AB  - AIM: This aim of this study was to identify the prevalence of vitamin D
      deficiency in pregnant women of a Wellington general practice where 10 cases of
      childhood rickets had been diagnosed over the past 3 years. METHODS: Ninety
      pregnant women were screened for vitamin D deficiency by measuring 25-hydroxy
      vitamin D by DiaSorin radioimmunoassay. Recruitment into the study was over a 12
      month period. A second appointment was arranged for clinical review and drawing
      of blood for parathyroid hormone, adjusted calcium, and alkaline phosphatase.
      RESULTS: 100% of women presenting to the general practice for antenatal care
      consented to the study. 87% of women had 25-hydroxy vitamin D levels below 50
      nmol/L. 61.2% of women had a vitamin D level below 25 nmol/L consistent with
      severe vitamin D deficiency. 10 women had an elevated parathyroid hormone
      consistent with secondary hyperparathyroidism. Only 22% of our patients were
      veiled, and included a diverse ethnic population, including African, Maori,
      European, Middle Eastern, and Polynesian women. CONCLUSIONS: Vitamin D deficiency
      is common in young pregnant women in this general practice, and it was not only
      confined to veiled women or women with dark skin. This highlights the magnitude
      of vitamin D deficiency in the pregnant population in a New Zealand setting; this
      vitamin D deficiency is responsible for the re-emergence of childhood rickets.

PMID- 16964293
TI  - The hedgehog regulated oncogenes Gli1 and Gli2 block myoblast differentiation by
      inhibiting MyoD-mediated transcriptional activation.
AB  - The mechanism by which activation of the Hedgehog (Hh) pathway modulates
      differentiation and promotes oncogenesis in specific tissues is poorly
      understood. We therefore, analysed rhabdomyosarcomas from mice that were
      haploinsufficient for the Hh-binding protein, Hip1, or for the Hh receptor,
      Patched 1 (Ptch1). Transfection of the Hh-regulated transcription factor Gli1,
      which is expressed in a subset of mouse and human rhabdomyosarcomas, suppressed
      differentiation of myogenic rhabdomyosarcoma lines generated from Hip1+/- and
      Ptch1+/- mice. The closely related factor, Gli2, had similar effects. Gli1 and
      Gli2 inhibited myogenesis by repressing the capacity of MyoD to activate
      transcription. Deletion analysis of Gli1 indicated that multiple domains of Gli1
      are required for efficient inhibition of MyoD. Gli1 reduced the ability of MyoD
      to heterodimerize with E12 and bind DNA, providing one mechanism whereby the Gli
      proteins modulate the activity of MyoD. This novel activity of Gli proteins
      provides new insights into how Hh signaling modulates terminal differentiation
      through inhibition of tissue-specific factors such as MyoD. This mechanism may
      contribute to the broad role of Hh signaling and the Gli proteins in
      differentiation decisions and cancer formation.

PMID- 16964297
TI  - Myotonic dystrophy in Otago, New Zealand.
AB  - AIMS: To determine the prevalence of myotonic dystrophy (DM) in Otago, the ethnic
      distribution of the disease, any founder effect, the complications and adequacy
      of health care, and the quality of life of sufferers in this region. METHODS: DM
      patients were identified through hospital records and assessed using a structured
      questionnaire, neurological examination, and review of hospital records. Quality
      of life was evaluated using the SF-36 Health Survey, and compared to patients
      with other neuromuscular conditions and New Zealand norms. RESULTS: 21 patients
      were identified, giving a prevalence of 11.6 per 100,000. All were of European
      descent. There was no evidence of a common ancestor. Not all patients had had
      essential investigations such as electrocardiogram and many had not been seen by
      the genetic service. DM patients had higher scores on the bodily pain subscale of
      the SF-36 Health Survey, compared to neuromuscular controls and the general
      population. Subjects differed significantly from New Zealand norms on four of the
      eight subscales. CONCLUSIONS: DM is relatively common in Europeans in Otago, but
      we found no cases in other ethnic groups. The disease affects aspects of quality
      of life, and management could be improved by use of a clinical care pathway.

PMID- 16964298
TI  - Reliability of ultrasound estimation of fetal weight in term singleton
      pregnancies.
AB  - AIM: To assess the reliability of ultrasound estimation of fetal weight
      undertaken antenatally at Wellington Hospital (Wellington City, New Zealand) in
      women with a singleton pregnancy = or >37 weeks gestation. METHOD: Data were
      collected retrospectively for pregnant women who had undergone ultrasound
      estimation of fetal weight <7 days prior to a term delivery (= or >37 weeks
      gestation) over the period of July 1998-June 2005. Stillbirths and multiple
      pregnancies were excluded. Ultrasound fetal weight estimations, calculated using
      a locally modified Woo formula, were compared with the infant's actual birth
      weight. RESULTS: A total of 1177 infants were studied. The mean absolute error
      and mean signed error (+/-SD) of ultrasound fetal weight estimations were 7.0+/
      5.7% and -0.2+/-9.0%, respectively (n=1177). Three-quarters of estimations were
      within 10% of birth weight. Ultrasonic estimation of fetal weight tended to
      overestimate the weight of small infants (<2500 g; mean signed error = +3.5%+/
      9.1%, n=98) and underestimate the weight of large infants (= or >4000 g; mean
      signed error = -3.3+/-8.7%, n=170). Both large and normal weight infants of women
      with diabetes tended to have their weight underestimated (mean signed error = 
      5.1+/-9.2%, n=48). Sensitivity, specificity, positive predictive value, and
      negative predictive value for ultrasonic detection of fetal weight = or >4000 g
      in non-diabetic women were 61%, 96%, 69%, and 94%, respectively. For detection of
      fetal weight = or >4500, the figures were 50%, 98%, 47%, and 98%, respectively.
      CONCLUSION: The accuracy of ultrasound estimations of fetal weight performed at
      Wellington Hospital within 7 days of delivery in term singleton pregnancies was
      at least similar and sometimes better than that reported in other studies. For
      one in four women, however, the fetal weight estimation was more than 10%
      different from the actual birth weight of their infant. Ultrasound measurements
      had a tendency to overestimate the weight of small infants while underestimating
      the weight of both large infants and the infants of diabetic mothers. As the
      reliability of ultrasound estimation of fetal weight to detect larger babies was
      poor, the use of such an objective measurement in the management of suspected
      macrosomia in term singleton pregnancies should be avoided.

PMID- 16964299
TI  - Medical image. Prandial tussiculation.

PMID- 16964300
TI  - Colitis and bronchiolitis obliterans organising pneumonia--the treatment or the
      disease?

PMID- 16964301
TI  - Quality improvement in New Zealand healthcare. Part 5: measurement for monitoring
      and controlling performance--the quest for external accountability.
AB  - In this fifth article in the Series on quality improvement, we examine
      organisational performance indicators, the consequences of their use, and what
      policy-makers and clinicians need to do to minimise their potential adverse
      effects. The Ministry of Health (MOH) and district health boards (DHB) are
      increasingly using performance indicators to measure activity and are looking at
      how they can be used to incentivise provider performance. Two different
      approaches are used: report cards (comparing individuals and organisational
      performance) and pay-for-performance (which provides financial payments for those
      organisations or individual providers who do what the funder wants). Given the
      United Kingdom and the United States experience with both approaches, it would
      seem prudent for New Zealand to proceed cautiously with using performance
      indicators to modify clinician behaviour. We argue that the integrity of the
      system overall is dependent on clinicians taking an interest in the indicators
      used by the Ministry of Health (MOH) and district health boards (DHBs).
      Furthermore, those using them must invest in learning about system variation and
      how this affects the external monitoring of performance.

PMID- 16964302
TI  - New Zealand's labour resources in general practice--should we worry?

PMID- 16964303
TI  - The few: New Zealand's diminishing number of rural GPs providing maternity
      services.

PMID- 16964304
TI  - New Zealand Food Safety Authority's response to the 'flies, fingers, fomites, and
      food' article on campylobacteriosis.

PMID- 16964305
TI  - Media report of rare rhabdomyolysis cases seems to have triggered reluctance
      among some New Zealanders to use statins.

PMID- 16964306
TI  - Tobacco harm reduction in New Zealand.

PMID- 16964307
TI  - What is common sense?

PMID- 16964308
TI  - What a performance--and response.

PMID- 16964309
TI  - Mast cell CD30 ligand is upregulated in cutaneous inflammation and mediates
      degranulation-independent chemokine secretion.
AB  - Mast cells are involved in many disorders where the triggering mechanism that
      leads to degranulation and/or cytokine secretion has not been defined. Several
      chronic inflammatory diseases are associated with increased mast cell numbers and
      upregulation of the TNF receptor family member CD30, but the role of elevated
      CD30 expression is poorly understood. Here we report what we believe to be a
      novel way to activate mast cells with CD30 that leads to degranulation
      independent secretion of chemokines. CD30 induced a de novo synthesis and
      secretion of the chemokines IL-8, macrophage inflammatory protein-1alpha (MIP
      1alpha), and MIP-1beta, a process involving the MAPK/ERK pathway. Mast cells were
      found to be the predominant CD30 ligand-positive (CD30L-positive) cell in the
      chronic inflammatory skin diseases psoriasis and atopic dermatitis, and both CD30
      and CD30L expression were upregulated in lesional skin in these conditions.
      Furthermore, the number of IL-8-positive mast cells was elevated both in
      psoriatic and atopic dermatitis lesional skin as well as in ex vivo CD30-treated
      healthy skin organ cultures. In summary, characterization of CD30 activation of
      mast cells has uncovered an IgE-independent pathway that is of importance in
      understanding the entirety of the role of mast cells in diseases associated with
      mast cells and CD30 expression. These diseases include Hodgkin lymphoma, atopic
      dermatitis, and psoriasis.

PMID- 16964310
TI  - TAT-mediated intracellular delivery of purine nucleoside phosphorylase corrects
      its deficiency in mice.
AB  - Defects in purine nucleoside phosphorylase (PNP) enzyme activity result in
      abnormal nucleoside homeostasis, severe T cell immunodeficiency, neurological
      dysfunction, and early death. Protein transduction domain (PTD) can transfer
      molecules into cells and may help restore PNP activity in cases of PNP
      deficiency. However, long-term use of PTD to replace enzymes in animal models or
      patients has not previously been described. We fused human PNP to the HIV-TAT PTD
      and found that the fusion with TAT changed the retention and distribution of PNP
      in PNP-deficient mice. TAT induced rapid intracellular delivery of PNP into
      tissues, including the brain, prevented urinary excretion of PNP, and protected
      PNP from neutralizing antibodies, resulting in significant extension of the
      enzyme's biological activity in vivo. Frequent TAT-PNP injections in PNP
      deficient mice corrected the metabolic disorder and immune defects with no
      apparent toxicity. TAT-PNP remained effective over 24 weeks of treatment,
      resulting in continued improvement in immune function and extended survival. Our
      data demonstrate that TAT changes the properties of PNP in vivo and that long
      term intracellular delivery of PNP by TAT corrects PNP deficiency in mice. We
      provide evidence to promote further use of PTD to treat diseases that require
      repeated intracellular enzyme or protein delivery.

PMID- 16964311
TI  - Knockdown expression and hepatic deficiency reveal an atheroprotective role for
      SR-BI in liver and peripheral tissues.
AB  - Scavenger receptor SR-BI has been implicated in HDL-dependent atheroprotective
      mechanisms. We report the generation of an SR-BI conditional knockout mouse model
      in which SR-BI gene targeting by loxP site insertion produced a hypomorphic
      allele (hypomSR-BI). Attenuated SR-BI expression in hypomSR-BI mice resulted in 2
      fold elevation in plasma total cholesterol (TC) levels. Cre-mediated SR-BI gene
      inactivation of the hypomorphic SR-BI allele in hepatocytes (hypomSR-BI
      KO(liver)) was associated with high plasma TC concentrations, increased plasma
      free cholesterol/TC (FC/TC) ratio, and a lipoprotein-cholesterol profile typical
      of SR-BI-/- mice. Plasma TC levels were increased 2-fold in hypomSR-BI and
      control mice fed an atherogenic diet, whereas hypomSR-BI-KO(liver) and SR-BI-/-
      mice developed severe hypercholesterolemia due to accumulation of FC-rich, VLDL
      sized particles. Atherosclerosis in hypomSR-BI mice was enhanced (2.5-fold)
      compared with that in controls, but to a much lower degree than in hypomSR-BI
      KO(liver) (32-fold) and SR-BI-/- (48-fold) mice. The latter models did not differ
      in either plasma lipid levels or in the capacity of VLDL-sized lipoproteins to
      induce macrophage cholesterol loading. However, reduced atherosclerosis in
      hypomSR-BI-KO(liver) mice was associated with decreased lesional macrophage
      content as compared with that in SR-BI-/- mice. These data imply that, in
      addition to its major atheroprotective role in liver, SR-BI may exert an
      antiatherogenic role in extrahepatic tissues.

PMID- 16964313
TI  - Variables associated with general practitioners' knowledge about and diagnostic
      skills for schizophrenia.
AB  - OBJECTIVE: This study investigated the level of knowledge about schizophrenia of
      primary care doctors working in the city of Brescia, Italy, and variables
      associated with better information. METHOD: The study design was devised after 2
      joint meetings with leading figures of the Italian College of General
      Practitioners. A cross-sectional evaluation of 215 general practitioners was
      performed (June 2002). A random subgroup was selected to participate in a 4-month
      retest session in order to evaluate the reliability of the schedule (October
      2002). The setting was the local health unit of Brescia, which involves 706
      primary care doctors working in the city and its province. Of these, 30.5% took
      part in the study. A structured self-report questionnaire (SAKS) was devised for
      this study. General practitioners were also asked to rate videotaped cases of 5
      patients with different DSM-IV diagnoses. The main outcome measures were the
      scores from subscales measuring knowledge of schizophrenia symptoms and signs,
      knowledge of antipsychotics and their adverse events, and correct diagnoses of 5
      videotaped cases. RESULTS: Primary care doctors identified positive (79.0%),
      negative (72.6%) and general (72.1%) symptoms of schizophrenia (p < .001). Of the
      5 cases on videotape, they correctly rated a mean of 3.1 cases. The mean
      percentage of anti-psychotics correctly identified was 34.1% (older) and 51.2%
      (novel) (p < .001). Better answers were given by doctors who knew the diagnostic
      criteria, had read books on psychiatry, and had attended previous courses.
      CONCLUSION: More teaching on the diagnosis of schizophrenia and clinical
      psychopharmacology should be given to general practitioners.

PMID- 16964312
TI  - CXCR2 ligands and G-CSF mediate PKCalpha-induced intraepidermal inflammation.
AB  - Transgenic mice overexpressing PKCalpha in the epidermis (K5-PKCalpha mice)
      exhibit an inducible severe intraepidermal neutrophilic inflammation and systemic
      neutrophilia when PKCalpha is activated by topical 12-O-tetradecanoylphorbol-13
      acetate (TPA). This inducible model of cutaneous inflammation was used to define
      mediators of skin inflammation that may have clinical relevance. Activation of
      cutaneous PKCalpha increased the production of the chemotactic factors cytokine
      induced neutrophil chemoattractant (KC) and macrophage inflammatory protein 2
      (MIP-2) in murine plasma. TPA treatment of cultured K5-PKCalpha keratinocytes
      also released KC and MIP-2 into culture supernatants through an NF-kappaB
      dependent pathway. MIP-2 and KC mediated the infiltration of neutrophils into the
      epidermis, since this was prevented by ablating CXCR2 in K5-PKCalpha mice or
      administering neutralizing antibodies against KC or MIP-2. The neutrophilia
      resulted from PKCalpha-mediated upregulation of cutaneous G-CSF released into the
      plasma independent of CXCR2. These responses could be inhibited by topical
      treatment with a PKCalpha-selective inhibitor. Inhibiting PKCalpha also reduced
      the basal and TNF-alpha- or TPA-induced expression of CXCL8 in cultured psoriatic
      keratinocytes, suggesting that PKCalpha activity may contribute to psoriatic
      inflammation. Thus, skin can be the source of circulating factors that have both
      local and systemic consequences, and these factors, their receptors, and possibly
      PKCalpha could be therapeutic targets for inhibition of cutaneous inflammation.

PMID- 16964314
TI  - Behavioral manifestations of sturge-weber syndrome: a case report.
AB  - Sturge-Weber syndrome is a neurocutaneous syndrome that manifests with vascular
      malformations involving the brain, eye, and skin. We report the case of an
      elderly patient suffering from Sturge-Weber syndrome who presented with episodic
      "angry" slapping symptoms to a psychiatric facility. A detailed history, physical
      and mental-state examination, and elaborate neuropsychological, neuroimaging, and
      laboratory assessment were undertaken. Clinically, the "angry" slapping episodes
      were diagnosed as complex partial seizures that improved in frequency with an
      increase in the dose of the antiepileptic medication. We also have attempted to
      identify the pathophysiology of such behavioral episodes in Sturge-Weber
      syndrome. This case report underlines the need for detailed laboratory and
      neuroimaging work-up in the elderly presenting with atypical symptoms. It also
      emphasizes the need for identification of and differentiation between similar
      atypical presentations and appropriate management of resources by the medical
      staff.

PMID- 16964316
TI  - The safety and tolerability of duloxetine compared with paroxetine and placebo: a
      pooled analysis of 4 clinical trials.
AB  - BACKGROUND: To compare the safety and tolerability of duloxetine with paroxetine
      and placebo in patients with major depressive disorder (MDD). METHOD: Data from
      four 8-week randomized, double-blind, placebo- and paroxetine-controlled studies
      of duloxetine for MDD (DSM-IV criteria) were pooled to compare the safety and
      tolerability of duloxetine 40 to 120 mg/day with paroxetine 20 mg q.d. Two of the
      4 trials included a 26-week extension. RESULTS: The pooled database included 1466
      patients (duloxetine, N = 736; paroxetine, N = 359; placebo, N = 371). No deaths
      occurred in the acute phase trials. Discontinuation rates for adverse events did
      not differ significantly for duloxetine, 8.0%, and paroxetine, 6.1%. Nausea was
      the most frequent treatment-emergent adverse event for duloxetine (duloxetine,
      14.4%; paroxetine, 12.0%; placebo, 3.8%). Blood pressure and corrected QT (QTc)
      interval changes were modest and did not differ significantly for the 3 groups.
      Mean heart rate increased slightly in the duloxetine group, 1.0 beat/minute, and
      did differ significantly (p < .001) from that in the paroxetine group, but the
      change is of doubtful importance. Mean changes in laboratory analytes remained
      within the reference range. Emergent sexual dysfunction was significantly greater
      among duloxetine- and paroxetine-treated patients than placebo-treated patients
      (p = .007 vs. duloxetine and p < .001 vs. paroxetine); however, it was
      significantly lower in duloxetine-treated patients than in paroxetine-treated
      patients (46.4% vs. 61.4%; p = .015). During the extension phase, weight gain (>=
      7% of initial body weight) was greater in both active-treatment groups than in
      the placebo group (duloxetine, 10.8%; paroxetine, 13.8%; placebo, 3.1%), but the
      active-treatment groups did not differ. CONCLUSIONS: Duloxetine is safe and well
      tolerated in patients with MDD, with safety and tolerability comparable to that
      of paroxetine.

PMID- 16964315
TI  - Human immunodeficiency virus and depression in primary care: a clinical review.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals are at
      increased risk of developing depression. Depressive syndromes in these patients
      pose a challenge both diagnostically and therapeutically. These syndromes reflect
      both the presence of preexisting mood disorders and the development of depressive
      syndromes subsequent to HIV infection. DATA SOURCES: A search of the literature
      to 2005 was performed using the PubMed and Ovid search engines. English- and
      Portuguese-language articles were identified using the following keywords: HIV or
      AIDS and depression, mental illness, suicide, fatigue, psychiatry, and drug
      interactions. Additional references were identified through bibliography reviews
      of relevant articles. DATA SYNTHESIS: The clinical presentation and differential
      diagnosis of depressive symptoms in HIV illness and the role of HIV in the
      development of these conditions are reviewed. Management issues including suicide
      assessment and treatment options are then discussed, and potentially important
      pharmacokinetic interactions are reviewed. CONCLUSIONS: Individuals with HIV show
      higher rates of depression. This phenomenon may be due to a preexisting
      psychiatric disorder or to the HIV infection. Untreated depression symptoms may
      lead to non-compliance with drug regimens or increased high-risk behaviors. Given
      the adverse sequelae of untreated depressions in HIV illness, identification and
      management of depression are integral components of comprehensive HIV care.

PMID- 16964317
TI  - Physician patterns of metabolic screening for patients taking atypical
      antipsychotics: a retrospective database study.
AB  - OBJECTIVE: The aim of this retrospective database study was to determine rates of
      screening for metabolic side effects by physician specialty in community hospital
      patients prescribed atypical antipsychotics. METHOD: A pharmacy database review
      identified patients who were prescribed atypical antipsychotics over a 6-month
      period from July 1, 2004, to December 31, 2004. This list of patients was then
      cross-referenced with the laboratory database to determine if screening
      laboratory tests for metabolic abnormalities had been ordered. RESULTS: 13% of
      patients prescribed atypical antipsychotics had fasting blood glucose levels
      measured during the study period. 30% of patients prescribed atypical
      antipsychotics also had lipid panels measured during the study period. Screening
      rates varied by specialty of physician. Physicians trained in combined family
      practice and psychiatry had the highest rate of screening, followed by other
      nonpsychiatric specialties. Psychiatrists had the lowest rate of screening.
      CONCLUSIONS: The rate of screening for metabolic side effects of atypical
      antipsychotics in this community hospital setting was low.

PMID- 16964320
TI  - Shared care.

PMID- 16964318
TI  - New developments in the treatment of attention-deficit/hyperactivity disorder in
      primary care.

PMID- 16964319
TI  - The recognition and management of psychological reactions to stroke: a case
      discussion.

PMID- 16964321
TI  - Sensitivity.

PMID- 16964322
TI  - High-dose olanzapine orally disintegrating tablets for treatment-resistant
      psychosis.

PMID- 16964323
TI  - Aerophagia as the initial presenting symptom of a depressed patient.

PMID- 16964325
TI  - MID and UspA1/A2 of the human respiratory pathogen Moraxella catarrhalis, and
      interactions with the human host as basis for vaccine development.
AB  - Moraxella catarrhalis IgD-binding protein MID is a 200 kDa autotransporter
      protein that exists as a oligomer and is governed at the transcriptional level.
      The majority of M. catarrhalis clinical isolates expresses MID. Two functional
      domains have been attributed to MID; MID764-913 functions as an adhesin and
      promotes the bacteria to attach to epithelial cells, whereas the IgD-binding
      domain is located within MID962-1200. In parallel, MID is stimulatory for B
      lymphocytes through the IgD B cell receptor. M. catarrhalis ubiquitous surface
      proteins A1 and A2 (UspA1/A2) are multifunctional outer membrane proteins that
      can bind complement and extracellular matrix proteins such as vitronectin and
      fibronectin. An interaction between the complement fluid phase regulator of the
      classical pathway, C4b binding protein (C4BP), and UspA1/A2 has also been
      observed. Moreover, UspA1/A2 has a unique feature to interfere with the innate
      immune system of complement by binding C3. Taken together, a growing body of
      knowledge on M. catarrhalis outer membrane proteins MID and UspA1/A2 and their
      precise interactions with the human host make them promising vaccine candidates
      in a future multicomponent vaccine.

PMID- 16964324
TI  - Carotenoid-membrane interactions in liposomes: effect of dipolar, monopolar, and
      nonpolar carotenoids.
AB  - Electron paramagnetic resonance (EPR) spin-labeling methods were used to study
      the effects of carotenoids on the physical properties of saturated
      phosphatidylcholine (PC) membranes to evaluate the contribution of the terminal
      hydroxyl groups of xanthophyll molecules to the carotenoid-membrane interaction.
      Effects of the dipolar, terminally dihydroxylated carotenoid lutein on membrane
      phase transition, fluidity, order, and polarity were compared with those of
      monopolar (beta-cryptoxanthin) and nonpolar (beta-carotene) carotenoids. These
      effects were monitored at the membrane center as a function of the amount of the
      carotenoid added to the sample and as a function of temperature for fluid-phase
      membranes. PC membranes with different thickness (from 12 to 22 carbons in alkyl
      chains) were used. Carotenoids shifted to lower temperatures and broadened the
      main phase transition of PC membranes. They decreased the membrane fluidity and
      increased the order of alkyl chains. Carotenoids also increased the
      hydrophobicity of the membrane interior. These effects were the strongest for
      lutein, significantly weaker for beta-cryptoxanthin, and negligible for beta
      carotene. They decreased with the increase of the membrane thickness. Presented
      results suggest that anchoring of carotenoid molecules at the opposite membrane
      surfaces by polar hydroxyl groups is significant in enhancing their effects on
      membrane properties. This manuscript also shows the ability of EPR spin-labeling
      methods to monitor different membrane properties that can be applied in
      biotechnological studies with the use of liposomes.

PMID- 16964326
TI  - Ganoderma lucidum extract stimulates glucose uptake in L6 rat skeletal muscle
      cells.
AB  - The effect of Ganoderma lucidum extract on glucose uptake was studied in L6 rat
      skeletal muscle cells. G. lucidum extract increased glucose uptake about 2-fold
      compared to control. The extract stimulated the activity of phosphatidylinositol
      (PI) 3-kinase which is a major regulatory molecule in the glucose uptake pathway.
      About 7-fold increased activity of a PI 3-kinase was observed after treatment
      with G. lucidum extract, whereas PI 3-kinase inhibitor, LY294002, blocked the G.
      lucidum extract-stimulated PI 3-kinase activity in L6 skeletal muscle cells.
      Protein kinase B, a downstream mediator of PI 3-kinase, was also activated by G.
      lucidum extract. We then assessed the activity of AMP-activated protein kinase
      (AMPK), another regulatory molecule in the glucose uptake pathway. G. lucidum
      extract increased the phosphorylation level of both AMPK alpha1 and alpha2.
      Activity of p38 MAPK, a downstream mediator of AMPK, was also increased by G.
      lucidum extract. Taken together, these results suggest that G. lucidum extract
      may stimulate glucose uptake, through both PI 3-kinase and AMPK in L6 skeletal
      muscle cells thereby contributing to glucose homeostasis.

PMID- 16964327
TI  - Mapping of a transcription promoter located inside the priA gene of the Bacillus
      subtilis chromosome.
AB  - The genome sequence of the Gram-positive soil bacterium Bacillus subtilis was
      completed in 1997 (Kunst et al., 1998) and the results included the
      identification of a putative transcription unit encompassing the yloI to yloS
      genes. Within this region of the B. subtilis chromosome 11 putative open reading
      frames were found with a wide diversity of probable functions. In this work we
      have analyzed transcription in the region of the priA-cpgA genes and we have
      mapped a promoter which is located inside the priA gene and its activity directs
      transcription of the def-yloM genes. Moreover, this transcript can be extended at
      low level to the prpC-priK-cpgA genes. Analysis of the sequence in proximity of
      the transcription start site revealed a sequence suitable for the housekeeping
      sigma(A) subunit of RNA polymerase. Analysis of the beta-glactosidase activity of
      transcription fusions revealed that the identified promoter is active at low
      level and its activity is increased during late exponential phase of growth.

PMID- 16964328
TI  - [Will we have new antibiotics?].

PMID- 16964329
TI  - [Individualized evaluation of the risk of infections in the oncohematologic
      patient].
AB  - In order to take the best approach to infection in the oncohematologic patient
      with fever, it is important to know not only how profound the neutropenia is and
      how long the patient has had it, but also the characteristics of the underlying
      disease, the immunosuppressive therapy received and the type of hematopoietic
      stem/progenitor cell transplantation performed. Moreover, is important to
      consider if these patients have any personal or familial history of infectious
      diseases. All these aspects let us calculate the net state of immunosuppression
      and the risk of infection, and provide us with information about the most
      probable etiology in each case and the best prophylaxis and treatment. In this
      study we review the more important advances in chemotherapy in recent years that
      will make it necessary in the future to change our prophylactic guidelines for
      more effective prevention of infection in the oncohematologic patient.

PMID- 16964330
TI  - Antifungal agents: mode of action in yeast cells.
AB  - Different kinds of mycoses, especially invasive, have become an important public
      health problem as their incidence has increased dramatically in the last decades
      in relation to AIDS, hematological malignancies, transplant recipients and other
      immunosuppressed individuals. Management of fungal infections is markedly limited
      by problems of drug safety, resistance and effectiveness profile. Current therapy
      for invasive mycoses uses a relatively reduced number of antifungal drugs, such
      as amphotericin B, fluconazole and itraconazole. Other new antifungal agents from
      old and new chemical families, like voriconazole, posaconazole, ravuconazole,
      caspofungin and micafungin, have been introduced into the armamentarium for
      fungal infections management. This review is focused on the mode of action of
      those antifungal drugs used against pathogenic yeasts. The interaction of
      amphotericin B with ergosterol and other membrane sterols results in the
      production of aqueous pores of drug and the ergosterol biosynthetic pathway is
      the target of the allylamines, phenylmorpholines and azole antifungal agents. The
      main molecular target of azole antifungals is the cytochrome P-450 protein
      Erg11p/Cyp51p. Echinocandins, a new class of antifungal drugs, are fungal
      secondary metabolites that act against beta-1-3-D-glucan synthesis. The
      phenylmorpholines, of which amorolfine is the sole representative in human
      therapy, affect two targets in the ergosterol pathway: Erg24p (delta 14
      reductase) and Erg2p (delta 8-delta 7 isomerase). The sordarins group are protein
      synthesis inhibitors that work by blocking the function of fungal translation
      elongation factor 2. Other protein inhibitors are zofimarin, BE31045, SCH57504,
      xylarin, hypoxysordarin and GR135402. In order to overcome the problems derived
      from the exploitation of azole drugs, macrolides and echinocandins, novel targets
      were explored. Proposed antifungal drugs have been developed against potential
      targets like the N-myristylation of fungal proteins, with inhibitors like
      myristate and histidine analogues or myristoylpeptide derivatives,
      aminobenzothiazoles, quinolines and benzofurans. Polymerization of cell wall
      carbohydrates from uridine di-phospho sugars is another potential target.

PMID- 16964331
TI  - [Antimicrobial susceptibility of Enterococcus faecalis isolated from patients in
      Cordoba (Spain)].
AB  - Enterococcus faecalis is a pathogenic microorganism. The aim of this
      investigation was to study the antibiotic susceptibility of the strains isolated
      in Cordoba in a 20-month period (January 2004 to August 2005). Susceptibility
      rates to betalactamics were 98% to ampicillin and 99% to amoxicillin/clavulanic
      acid; high-dose aminoglycosides (streptomycin 1000 microg and gentamycin 500
      microg) obtained 56% and 76%, respectively. We found no strains resistant to
      glycopeptides (vancomycin and teicoplanin) or to linezolid.

PMID- 16964332
TI  - Prevalence of beta-lactams resistance among Escherichia coli clinical isolates
      from a hospital in Algiers.
AB  - A high prevalence of beta-lactams resistance among Enterobacteriaceae have been
      reported worldwide; however, there are not sufficient data on this issue in
      Algeria. beta-Lactams susceptibility of 203 Escherichia coli clinical isolates
      was determined by agar diffusion method, and production of extended-spectrum beta
      lactamases (ESBL) was screened by double-disk synergy test. This analysis showed
      five well-defined phenotypes: 1) 62 isolates (30.5%) were susceptible to all beta
      lactams; 2) 135 isolates (66.5%) presented a broad-spectrum beta-lactamases
      phenotype (BSBL); 3) three isolates (1.5%) were defined as producing ESBLs; 4)
      two isolates (1%) were AmpC cephalosporinase producers; and 5) one isolate (0.5%)
      presented a phenotype of cell-decreased permeability to beta-lactams. Isoelectric
      focusing revealed beta-lactamases with isolectric points of 5.4 or 7.6 for
      isolates with BSBL phenotype; approximately 9.0 for two ESBL isolates; 5.4, 7.6
      and approximately 9.0 for the remaining ESBL isolate; and 5.4 and approximately
      9.0 for the AmpC isolates. The cefotaxime hydrolysis corresponds to the basic
      bands with an isoelectric point of approximately 9.0. Conjugation assay showed
      transfer of penicillinase and AmpC resistance phenotypes and their corresponding
      beta-lactamases to recipient E. coli BM21 in association with plasmids of 71.4 kb
      for the AmpC isolates and from 40-56 kb for penicillinase isolates. This result
      showed that the AmpC phenotype is plasmid mediated. ESBL isolates were found not
      to transfer their resistance through conjugation experiment. Polymerase chain
      reaction (PCR) experiments using primers specific to blaTEM, blaAmpC and blaCTX-M
      genes showed specific amplification with blaCTX-M primer for two ESBL isolates;
      blaTEM and blaCTX-M for the remaining ESBL isolate; and blaTEM and blaAmpC for
      the AmpC isolates and their corresponding transconjugants. The study showed a
      high rate of isolates producing penicillinase, and low frequencies of AmpC and
      ESBL phenotypes. AmpC beta-lactamases were plasmid mediated, and ESBLs belong to
      the CTM-M type.

PMID- 16964333
TI  - Molecular epidemiology of drug-resistant Salmonella Typhimurium in Spain.
AB  - One hundred and forty-seven Salmonella serotype Typhimurium strains isolated in
      three provinces in the midwest of Spain were studied. Of these, 93.6% were drug
      resistant. There were two predominant resistance phenotypes: 43 isolates (29.3%)
      were resistant to amoxicillin, tetracyclines, chloramphenicol, streptomycin and
      sulphamethoxazole and 27 isolates (18.4%) to amoxicillin, amoxicillin/clavulanic
      acid, tetracyclines, chloramphenicol, streptomycin and sulphamethoxazole.
      Randomly amplified polymorphic DNA (RAPD) analysis and pulsed field gel
      electrophoresis (PFGE) were performed for molecular typing. Thirty-six DNA band
      profiles were differentiated by RAPD, and 38 by PFGE. We found a high level of
      clonality; 27% of strains were identical by both methods. There were additional
      smaller clonal lines within every area. The highest discriminatory power was
      obtained with PFGE, but the greatest degree of genetic diversity was observed
      among Salmonella Typhimurium using both RAPD and PFGE.

PMID- 16964334
TI  - [Detection and typing by molecular biology of human papillomavirus in genital
      samples].
AB  - Recently, there has been a marked increase in human papillomavirus (HPV)
      infection, and the etiological relationship between some HPV genotypes and
      genital cancer has been confirmed. Therefore, we used current molecular biology
      techniques to evaluate the prevalence of these viruses and their genotype in
      genital samples. We processed 401 genital samples from 281 women and 120 men, all
      with a diagnosis compatible with HPV infection. Virus was detected using PCR, and
      positive samples were typed using an array technique which enabled us to detect
      the 35 most common types of mucous-associated HPV. Of the 401 patients studied,
      185 (46.1%) were positive, and only one type of HPV was detected in 133 cases. We
      found that 41.6% of the women and 56.7% of the men were positive. A total of 260
      HPVs were typed; 154 were high oncogenic risk. They infected 16 men (23.5%) and
      88 women (75.2%). The difference was statistically significant (p<0.001). Type 6
      HPV was the most frequently detected en 64 cases, followed by HVP 16 in 52 cases.
      We found a 46% prevalence of HPV infection. More than half of these patients were
      infected by high-risk HPV. The presence of high-risk HPV was significantly higher
      in women.

PMID- 16964335
TI  - [Antimicrobial treatment of COPD in the elderly].

PMID- 16964336
TI  - [Evaluation of a rapid detection method for broad-spectrum beta-lactamases using
      a chromogenic cephalosporin].

PMID- 16964337
TI  - [The keys of an era: Wright and Fleming].

PMID- 16964338
TI  - [Impact of Nuklearmedizin in 2,980].

PMID- 16964339
TI  - Is there a benefit of 131 I-MIBG therapy in the treatment of children with stage
      4 neuroblastoma? A retrospective evaluation of The German Neuroblastoma Trial
      NB97 and implications for The German Neuroblastoma Trial NB2004.
AB  - AIM: (131)I-meta-iodobenzylguanidine ((131)I-MIBG) therapy has been used in
      neuroblastoma treatment for many years but its value in high intensive first line
      treatment protocols is not exactly known. PATIENTS, METHODS: Stage 4
      neuroblastoma patients >1 year with (123)I-MIBG positive residual disease
      (primary tumour and/or metastasis) after complete induction chemotherapy
      according to the German neuroblastoma trial NB97 were retrospectively analyzed.
      RESULTS: One-hundred-eleven patients had (123)I-MIBG positive residual disease
      after complete induction chemotherapy. Forty patients received (131)I-MIBG
      therapy using a median activity of 0.44 GBq/kg body weight. By univariate
      analysis, patients who underwent (131)I-MIBG therapy had a better 3-year event
      free survival (3-y-EFS 46 +/- 8%) and 3-year overall survival (3-y-OS 58 +/- 9%)
      than 71 patients without (131)I-MIBG therapy (3-y-EFS 19 +/- 5%, p = 0.003; 3-y
      OS 43 +/- 6%, p = 0.037). However, subgroup analysis of 66 patients who underwent
      high dose chemotherapy with autologous stem cell transplantation (ASCT) during
      treatment found a very similar outcome with (131)I-MIBG therapy (3-y-EFS 49 +/-
      9%, 3-y-OS 59 +/- 10%) and without (131)I-MIBG therapy (3-y-EFS 33 +/- 9%, p =
      0.171; 3-y-OS 59 +/- 9%, p = 0.285) due to the dominating effect of ASCT. By
      multivariate analysis, (131)I-MIBG therapy had no impact on EFS (p = 0.494) and
      OS (p = 0.891). Only ASCT, external beam radiation therapy and MYCN amplification
      were important for EFS and OS. CONCLUSIONS: An independent advantage of I-131
      MIBG therapy could not be proven in this retrospective analysis. The ongoing
      German Neuroblastoma Trial NB2004 will address the influence of (131)I-MIBG
      therapy with emphasis on tumour dosimetry.

PMID- 16964340
TI  - High energy probe for detecting lymph node metastases with 18F-FDG in patients
      with head and neck cancer.
AB  - AIM: of this study was to validate a newly developed high energy probe (positron
      emission probe, PEP) optimised for localising PET tracers in vivo. PATIENTS AND
      METHODS: Physical investigations included determination of full width at half
      maximum (FWHM) values at a distance of 1 cm and angular resolution using
      different point sources. Values obtained with the new probe were compared to
      those of a conventional gamma probe (CGP). Additionally, PET studies were
      performed in 36 patients (6 women, 30 men) with proven head and neck cancer and
      suspected lymph node metastases (Axis, Marconi/Philips) after administering 250
      320 MBq (18)F-FDG. Subsequent to PET investigations (18)F-FDG uptake in cervical
      regions was measured using the PEP. PEP investigations were carried out
      bilaterally in 5 lymph node (LN) levels (Robbins' classification of the neck).
      Results of probe studies were correlated with visual and semiquantitative PET
      evaluations, US and histological findings. RESULTS: FWHM of the new probe was 7
      mm (CGP 22 mm) at 662 keV ((137)Cs) and angular resolution resulted in 8 degrees
      (CGP 60 degrees ). In 29 out of 36 patients LN metastases were suspected due to
      ultrasound investigations. After neck dissection, histology confirmed LN
      metastases in 21 patients. Sensitivity (sens.) of US amounted to 95% and
      specificity to 40%. In 18/21 patients LN metastases were detected by PET (sens.
      86%). PET scans failed to diagnose the LN status correctly in 6/36 patients
      (accuracy 83%). Employing the PEP probe in 20/21 patients LN metastases were
      identified (sens. 95%), and LN status was determined accurately in 29/36 patients
      (accuracy 81%). Tumour/background ratios of PEP measurement and results of
      semiquantitative PET analyses were comparable. CONCLUSIONS: PEP measurement is a
      promising method for preoperative planning of the extent of neck dissection in
      patients with head and neck cancer and further for radioguided localising PET
      tracer accumulation during surgery.

PMID- 16964341
TI  - Somatostatin receptor scintigraphy in patients with cat-scratch disease.
AB  - AIM: Somatostatin receptor scintigraphy images various neoplastic, granulomatous,
      and auto-immune diseases. Cat-scratch disease in an infectious granulomatous
      disease usually affecting the lymphnodes. It is not known whether cat-scratch
      disease provides positive somatostatin receptor scintigrams. PATIENTS, METHODS:
      Twelve patients with lymphadenitis and suspected cat-scratch disease were
      investigated by immunofluorescence antibody testing and somatostatin receptor
      scintigraphy. Suppurated lymphnodes were extracted or drained and Bartonella
      henselae specific PCR was then performed. RESULTS: Eleven of 12 patients showed
      IgG antibodies against B. henselae. SRS showed positive scintigraphic results in
      6 of 11 patients with CSD. B. henselae DNA was detected in tissue of lymphnodes
      from 4 of 5 patients with lymphnode extraction or lymphnode drainage. SRS
      demonstrated positive scintigrams in all patients with a positive PCR. In one
      patient with suspected CSD SRS was negative as well as antibody testing.
      CONCLUSION: Somatostatin receptor scintigraphy correlated with positive
      Bartonella henselae specific PCR tests and positive Bartonella henselae specific
      antibody tests in patients with CSD.

PMID- 16964342
TI  - FDG gamma camera PET equipped with one inch crystal and XCT. Assessment of
      myocardial viability.
AB  - Metabolic imaging with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) is actually
      considered as the best method to detect and quantitatively assess myocardial
      tissue viability. The aim of this study was to investigate the accuracy of FDG
      gamma camera positron emission tomography (GCPET) imaging equipped with one inch
      NaI crystals in comparison to FDG dedicated PET (dPET) imaging as a "gold
      standard" in phantom and clinical studies. PATIENTS, METHODS: Nineteen patients
      with coronary artery disease (CAD) underwent both imaging modalities. Phantom and
      clinical GCPET imaging were performed with a dual-headed, coincidence based gamma
      camera equipped with 1 inch thick NaI crystals and an x-ray tube (XCT) for
      attenuation correction (AC), as well as with a dedicated PET scanner with AC.
      (99m)Tc tetrofosmin single-photon emission tomography (SPET) studies were
      performed for assessment of myocardial perfusion, with AC. RESULTS: Phantom
      studies showed a significant relation in segmental activity between FDG imaging
      with AC using GCPET and dPET (r = 0.91, p < 0.001). In clinical studies with AC
      correlation coefficients of mean segmental FDG uptake and regional defect size
      were r = 0.87 (p < 0.0001) and r = 0.83 (p < 0.0001), respectively. In regional
      analysis close agreement was even found in the most attenuated regions of the
      heart if AC was used in GCPET imaging. The overall agreement for detection of
      viable myocardium was 81% between FDG-dPET (AC) and FDG-GCPET (AC) and 74%
      between FDG-dPET (AC) and FDG-GCPET (NC). CONCLUSION: This study suggests that
      the assessment of myocardial metabolism by means of FDG is feasible with a
      coincidence based gamma camera equipped with 1 inch thick NaI crystals if AC is
      performed. The results reveal a close concordance and agreement between FDG-dPET
      (AC) and FDG-GCPET (AC) as compared to FDG-GCPET (NC).

PMID- 16964343
TI  - Attenuation correction for myocardial perfusion imaging. A comparison between
      SPECT and PET imaging by polar map analysis.
AB  - AIM: We investigated the impact of photon attenuation in myocardial perfusion
      imaging with SPECT and PET in patients with coronary artery disease. In fact, the
      regional tracer distribution can be quantitatively assessed by polar map analysis
      if the effects of photon attenuation are accounted for. PET imaging permits
      accurate measurement of and correction for photon attenuation, whereas results of
      attenuation correction in SPECT imaging have been inconsistent. PATIENTS,
      METHODS: We compared photon attenuation in resting perfusion imaging studies with
      SPECT ((99m)Tc-sestamibi) and PET ((13)N-ammonia) from 21 patients. Transaxial
      images were reconstructed with and without attenuation correction and reoriented
      into short axis images. Polar map analysis was utilized to generate regional
      tracer uptake in six anatomical segments. RESULTS: Average segmental photon
      attenuation calculated as the ratio of counts in corrected and uncorrected images
      was 7.2 +/- 1.4 in SPECT and 14.0 +/- 3.1 in PET imaging (p < 0.01). This
      attenuation factor was significantly related to body mass index for both methods
      (p < 0.001). While attenuation correction for SPECT imaging did compensate for
      attenuation effects in the inferior wall (from -15% to +6% vs. PET), relative
      tracer uptake in the anterior wall in SPECT images was significantly reduced
      after attenuation correction (from -2% to -18% vs. PET, p < 0.01). CONCLUSION:
      Differential effects of attenuation correction for myocardial SPECT perfusion
      imaging need to be considered when algorithms designed to compensate effects of
      photon attenuation in SPECT imaging are employed in clinical practice.

PMID- 16964344
TI  - Evaluation of patients with liver metastases from colorectal cancer for locally
      ablative treatment with laser induced thermotherapy. Impact of PET with 18F
      fluorodeoxyglucose on therapeutic decisions.
AB  - PURPOSE: Before locally ablative treatment of colorectal liver metastases,
      patients have to be carefully evaluated to decide whether this is the adequate
      therapy. In this study we determined the value of FDG-PET in comparison to
      conventional staging procedures. PATIENTS, METHODS: In 68 consecutive patients
      referred for laser induced thermotherapy (LITT) of liver metastases from
      colorectal cancer, pretherapeutic staging with conventional imaging (thoracic and
      abdominal CT, liver MRI, chest X-ray) and FDG-PET was performed. The examinations
      were analysed separately and blinded. Based on the staging information,
      therapeutic decisions were made by an interdisciplinary review board according to
      a standardized algorithm. The results were compared between conventional imaging
      and FDG-PET, and were validated by clinical follow up data and histopathology,
      respectively. RESULTS: On FDG-PET 210 lesions were interpreted as tumour
      manifestations. 48 of these were not seen on conventional imaging (true positive,
      n = 46). In contrast, 24 lesions were visualized by conventional imaging only
      (true positive, n = 12). Compared to conventional imaging, discrepant findings on
      FDG-PET led to treatment modifications in 25 patients (37%); these were correct
      in 20/25 patients. According to the actual treatment course, the inadequate
      treatment modifications in the remaining 5 patients were avoided by further
      diagnostic procedures (i.e. biopsies). CONCLUSION: In the evaluation of patients
      with known liver metastases from colorectal cancer before LITT, FDG-PET depicts
      relevant findings subsidiary to conventional imaging and thus is of high value
      for therapeutic decision making.

PMID- 16964345
TI  - Therapy of hepatocellular carcinoma with iodine-131-lipiodol. Results in a large
      German cohort.
AB  - AIM: To evaluate the efficacy and tolerance of iodine-131-lipiodol ((131)I
      lipiodol) for hepatocellular carcinoma (HCC) in German long term patients and
      comparison with medically treated controls. PATIENTS, METHODS: 38 courses of
      intra-arterial (131)I-lipiodol therapy with a total activity up to 6.7 GBq were
      performed in 18 patients with HCC (6 with portal vein thrombosis). Liver and
      tumour volume and lipiodol deposition were measured by computed tomography and
      (131)I activity by scintigraphy. Therapeutic efficacy was determined by tumour
      volume change and matched-pairs analysis in comparison to medically (i.e.
      tamoxifen or medical support) treated patients. RESULTS: Tumour volume decreased
      in 20/32 index nodules (63%) after the first course. Repeated therapy frequently
      resulted in further tumour reduction. Overall response to treatment was partial
      in 11 nodules, minor response in 4 nodules, and disease was stable in 12 and
      progressive in 5. Significant response was associated with pretherapeutic nodule
      volume up to 150 ml (diameter of 6.6 cm). Survival rate after 3, 6, 9, 12, 24 and
      36 months was 78, 61, 50, 39, 17, and 6%. Matched-pairs analysis of survival
      revealed (131)I-lipiodol to be superior to medical treatment. The most important
      side effect was a pancreatitis-like syndrome whereas overall tolerance was good.
      CONCLUSION: The long term results confirm that HCC therapy with (131)I-lipiodol
      is effective and probably superior to medical treatment. Tumour nodules of up to
      6 cm diameter are well suited for this therapy even in the presence of portal
      vein thrombosis.

PMID- 16964346
TI  - The cooperation of medical informatics, biometry and epidemiology.

PMID- 16964347
TI  - Standardized documentation of drug recommendations in discharge letters--a
      contribution to quality management in cooperative care.
AB  - OBJECTIVES: To analyze the necessity and potential usefulness of a computerized
      physician order entry (CPOE) system in supporting the writing of
      pharmacotherapeutic recommendations in discharge letters. METHODS: Systematic
      analysis of drug recommendations in discharge letters of a hospital providing
      tertiary care, structured interviews with in-hospital prescribers, and focus
      groups with general practitioners who admit patients to this hospital. RESULTS:
      We analyzed 1800 randomly selected discharge letters, 1205 of which contained
      pharmacotherapeutic recommendations. The frequencies, structure, and quality of
      these recommendations varied considerably between departments. Nearly 16% of the
      recommendations contained both proprietary (brand) and non-proprietary names
      (active ingredient). Interviewed clinicians expressed interest in CPOE systems
      that check for contraindications and interactions between drugs, suggest cheaper
      products, and automatically insert active ingredients when omitted. The focus
      group sessions confirmed that the pharmacotherapeutic recommendations in current
      discharge letters do not effectively support daily clinical practice.
      CONCLUSIONS: Documenting active ingredients as well as brand names in drug
      therapy recommendations is currently not part of clinical practice. Computerized
      decision support can help to optimise the structure and communication of
      therapeutic information across interfaces and can be a quality factor with
      considerable influence on process quality, outcome quality, and costs of
      cooperative patient care.

PMID- 16964348
TI  - Semantic interoperability--HL7 Version 3 compared to advanced architecture
      standards.
AB  - OBJECTIVES: To meet the challenge for high quality and efficient care, highly
      specialized and distributed healthcare establishments have to communicate and co
      operate in a semantically interoperable way. Information and communication
      technology must be open, flexible, scalable, knowledge-based and service-oriented
      as well as secure and safe. METHODS: For enabling semantic interoperability, a
      unified process for defining and implementing the architecture, i.e. structure
      and functions of the cooperating systems' components, as well as the approach for
      knowledge representation, i.e. the used information and its interpretation,
      algorithms, etc. have to be defined in a harmonized way. Deploying the Generic
      Component Model, systems and their components, underlying concepts and applied
      constraints must be formally modeled, strictly separating platform-independent
      from platform-specific models. RESULTS: As HL7 Version 3 claims to represent the
      most successful standard for semantic interoperability, HL7 has been analyzed
      regarding the requirements for model-driven, service-oriented design of semantic
      interoperable information systems, thereby moving from a communication to an
      architecture paradigm. The approach is compared with advanced architectural
      approaches for information systems such as OMG's CORBA 3 or EHR systems such as
      GEHR/openEHR and CEN EN 13606 Electronic Health Record Communication. CONCLUSION:
      HL7 Version 3 is maturing towards an architectural approach for semantic
      interoperability. Despite current differences, there is a close collaboration
      between the teams involved guaranteeing a convergence between competing
      approaches.

PMID- 16964349
TI  - The semantics of procedures and diseases in SNOMED CT.
AB  - OBJECTIVES: SNOMED CT is emerging as a reference terminology for the entire
      health care process. It claims to be founded on logic-based modelling principles.
      In this article, we analyze a special encoding scheme for diseases and procedures
      in SNOMED CT, the so-called relationship groups (RGs), which had been devised to
      avoid ambiguities in definitions. METHODS: We reformulate SNOMED CT's
      relationship groups in the format of description logics in order to check whether
      RGs serve the needs they were designed for. RESULTS: We show that a considerable
      proportion of relationship groups represent hidden mereological relations. We
      also report discrepancies encountered between the defined semantics of many
      SNOMED CT terms and their intuitive meaning, as well as inconsistencies detected
      between the definition of various complex composed terms and the definition of
      their top-level parents. CONCLUSIONS: We formulate recommendations for improving
      SNOMED CT by replacing most occurrences of relation groups by formally more
      adequate "part-of" relations.

PMID- 16964350
TI  - Standardized exchange of clinical documents--towards a shared care paradigm in
      glaucoma treatment.
AB  - OBJECTIVES: The exchange of medical data from research and clinical routine
      across institutional borders is essential to establish an integrated healthcare
      platform. In this project we want to realize the standardized exchange of medical
      data between different healthcare institutions to implement an integrated and
      interoperable information system supporting clinical treatment and research of
      glaucoma. METHODS: The central point of our concept is a standardized
      communication model based on the Clinical Document Architecture (CDA). Further, a
      communication concept between different health care institutions applying the
      developed document model has been defined. RESULTS: With our project we have been
      able to prove that standardized communication between an Electronic Medical
      Record (EMR), an Electronic Health Record (EHR) and the Erlanger Glaucoma
      Register (EGR) based on the established conceptual models, which rely on CDA
      rel.1 level 1 and SCIPHOX, could be implemented. The HL7-tool-based deduction of
      a suitable CDA rel.2 compliant schema showed significant differences when
      compared with the manually created schema. Finally fundamental requirements,
      which have to be implemented for an integrated health care platform, have been
      identified. CONCLUSIONS: An interoperable information system can enhance both
      clinical treatment and research projects. By automatically transferring screening
      findings from a glaucoma research project to the electronic medical record of our
      ophthalmology clinic, clinicians could benefit from the availability of a
      longitudinal patient record. The CDA as a standard for exchanging clinical
      documents has demonstrated its potential to enhance interoperability within a
      future shared care paradigm.

PMID- 16964351
TI  - Evaluation of health-related Internet use in Germany.
AB  - OBJECTIVE: An eHealth survey was conducted in a major Bavarian region in order to
      evaluate health-related Internet use in Germany. METHODS: A specific
      questionnaire was developed by the authors to collect sociodemographic data as
      well as data on general and health-related Internet use. This questionnaire was
      distributed to patients visiting medical practices in the above mentioned
      Bavarian region. RESULTS: Whereas many Internet users look for health-related
      information and products on the Internet, more advanced web-based techniques such
      as chat rooms and electronic patient records are hardly used. CONCLUSIONS:
      Although modern information technologies have the potential to enable citizens to
      handle their own health-related information in a self-determined and informed
      manner, at present the general population in Germany is hardly taking this
      opportunity.

PMID- 16964352
TI  - Computer-assisted analysis of 4D cardiac MR image sequences after myocardial
      infarction.
AB  - OBJECTIVES: Spatial-temporal MR image sequences of the heart contain information
      about shape and motion changes and pathological structures after myocardial
      infarction. In this paper a Heart Analysis Tool (HeAT) for the quantitative
      analysis of 4D MR image sequences of infarct patients is presented. METHODS: HeAT
      supports interactive segmentation of anatomical and pathological structures.
      Registration of Cine- and DE-MR image data is applied to enable their combined
      evaluation during the analysis process. Partitioning of the myocardium in
      segments enables the analysis with high local resolution. Corresponding segments
      are generated and used for inter/intrapatient comparison. Quantitative parameters
      were extracted and visualized. RESULTS: Parameters like endocard movement in the
      infarcted area of six infarct patients were computed in HeAT. Parameters in the
      infarct area show the expected dysfunctional characteristics. Based on theses
      parameters passive endocardial movement and myocardial areas with decreased
      contraction could be identified. CONCLUSION: In contrast to other software tools
      HeAT supports the combination of contour information of Cine-MR and DE-MR, local
      analysis with high resolution and inter/intra patient comparison. HeAT enables an
      observer-independent evaluation of the complex cardiac image data. Using HeAT in
      further studies can increase the understanding of left ventricle (LV) remodeling.

PMID- 16964353
TI  - Pre-operative dynamic interactive exploration of complex articular fractures
      using a novel 3D navigation tool.
AB  - OBJECTIVES: Trauma surgeons possess specific anticipative pathoanatomical and
      procedural domain knowledge that can be used for information extraction from
      original CT image data. This knowledge so far remains unused in clinical workflow
      and surgeons do not take an active part in the process of image generation and
      processing. The objectives of our work are to propose and employ a strategy to
      directly involve surgeons in a dynamic image exploration process and to
      exemplarily assess the clinical use of this approach for pre-operative diagnosis
      of complex articular fractures. METHODS: We used an interactive 3D navigation
      tool with a novel human-computer interface for the exploration of articular
      fractures of two selected anatomical structures. The system offers dynamic
      interaction with a virtual 3D reconstruction model and the possibility to create
      on-the-fly oblique multiplanar reformations by tracking hand movements. Three
      expert surgeons performed exemplary explorations and rated the use of the method
      for preoperative diagnosis in informal interviews. RESULTS: The approach and the
      system were well received by the three surgeons. The dynamic interaction was
      rated to be helpful in understanding fracture morphology. Two examples--a radius
      and a calcaneal fracture--are presented. CONCLUSIONS: Surgeons with their
      specific domain knowledge should be involved in the process of image processing.
      The benefit of using oblique multiplanar reformations for pre-operative planning
      in articular fractures appears to be substantial and they should therefore be
      included in radiological and surgical textbooks. Further evaluation is necessary
      to assess the use of interactive exploration systems in routine diagnosis.

PMID- 16964354
TI  - An e-learning platform for guideline implementation--evidence- and case-based
      knowledge translation via the Internet.
AB  - OBJECTIVES: Effective knowledge translation in medicine is an essential element
      of a modern health care system. Evidence-based clinical practice guidelines
      (CPGs) are considered relevant instruments for the transfer of knowledge into
      clinical practice. To improve this transfer we have created Internet-based
      continuing medical education (CME) modules and online case-based learning
      objects. METHODS: Building upon existing CPGs, an e-learning platform including a
      multi-step review process was developed to generate CME modules. These CME
      modules were presented through a modified content management system (CMS) that
      fulfils specific requirements of CME. An online questionnaire using a four-point
      Likert scale was designed to receive mandatory feedback from participating
      physicians. In the second step of development, case-based learning objects were
      added to the CMS. RESULTS: Existing clinical practice guidelines allowed a rapid
      development of CME modules specific to individual clinical indications. The
      modified CMS proved to be technically stable but also resource-intensive. 3105
      physicians registered and used the platform between June 2003 and April 2005. 95%
      of the physicians expressed positive feedback in an evaluation questionnaire;
      only 35% of physicians actually used the corresponding CPGs in practice.
      Suggestions from the CME users led to the development of interactive medical case
      based learning objects related to the main topics of the CPGs. CONCLUSIONS: To
      support the implementation of CPGs, an Internet platform for CME including case
      based learning objects and examination tests was developed. An interactive online
      CME platform can support active learning and may establish an additional stimulus
      for knowledge translation into daily medical practice.

PMID- 16964355
TI  - A simple method to estimate tobacco-related lung cancer deaths based on smoking
      prevalence data.
AB  - OBJECTIVE: Tobacco is the major cause of cancer and a relevant risk factor for
      several other chronic diseases. Due to the epidemiological transition in
      developing countries with overall increasing life expectancy there is an
      increasing relevance of chronic diseases to the total burden of diseases.
      Furthermore, there are indications for a rise in the consumption of tobacco
      products in developing countries. Since in Africa data on smoking prevalence are
      scarce and cancer diagnosis is often imprecise or missing, it is difficult to
      estimate the current and future number of cancer cases attributable to tobacco
      smoking. In this paper, we present an approach to estimate the effects of smoking
      on lung cancer in selected developing countries in Africa. METHODS: We combined
      data on smoking prevalence from different African countries with estimates on age
      specific lung cancer rates in smokers and non-smokers from industrialized
      countries and data on age and sex distribution in African countries. We perform a
      sensitivity analysis to evaluate the effect of the assumptions necessary for the
      procedure. RESULTS: If the smoking prevalence in African countries will remain on
      the current level, we estimate age-specific lung cancer rates lower than those in
      Germany. Despite the relatively small proportion of adults aged 50 and more which
      is the age when most cancer cases occur, there is an appreciable number of deaths
      from lung cancer that could be prevented when smoking prevalence could be
      reduced. Depending on assumptions we estimate up about 50,000 lung cancer deaths
      per year in Africa, most of which could be prevented. CONCLUSIONS: Efforts for
      smoking prevalence reduction are much more needed in the developing world. Better
      and more comprehensive data on smoking are needed for more precise estimates.

PMID- 16964356
TI  - The attributable risk in a multifactorial situation--evaluation of different
      methods of partitioning.
AB  - OBJECTIVES: Different approaches to partition the attributable risk into exposure
      specific components are methodologically evaluated. METHODS: Two methods of
      partitioning the attributable risk in a multifactorial situation have been
      suggested. One is based on a solution adopted from game theory, the Shapley
      value, whereas the other recently suggested approach uses a heuristically
      motivated proportional weighting scheme. These two concepts are reviewed and
      compared in a situation with three exposure factors. A hypothetical numerical
      example is discussed illustrating differences in the case of complex interaction
      structures. RESULTS: The two methods are found to differ in two critical features
      that affect the outcome of partitioning: i) including or ignoring the full
      interaction structure between exposure factors involved in the partitioning, ii)
      using an equal or proportional weighting scheme for the marginal excess risks of
      the exposures. As a result, not only the individual partial attributable risks
      for the exposure factors may be quantitatively different between the methods, but
      also their ranking depends on the partitioning approach. CONCLUSIONS: The
      epidemiologic properties of the partitioning procedure based on the Shapley value
      are known and fit to the needs of epidemiologic applications. The alternative
      approach recently suggested can lead to considerably different results. As long
      as its epidemiologic properties are not fully understood, the traditional
      partitioning method should be given preference in practical applications.

PMID- 16964357
TI  - Statistical methods for the validation of questionnaires--discrepancy between
      theory and practice.
AB  - OBJECTIVES: Questionnaires used in epidemiological studies should be validated.
      However, unclarity exists about the appropriate statistical methods and
      interpretation of validation studies. Thus, we investigated the theory and
      practice of statistical evaluation approaches. METHODS: Using three platforms, a
      literature review, own simulations, and a validation study performed by
      ourselves, we worked out relevant limitations, advantages, and new important
      aspects of evaluation methods. RESULTS: Our systematic literature review, based
      on physical activity questionnaires, revealed that correlation coefficients are
      still the common approach in validation studies, found in 41 of 46 reviewed
      publications (89.1%). This practice has been criticized in the theoretically
      oriented literature for more than 20 years. Appropriate evaluation methods as
      recommended by Bland and Altman were found in only ten publications (21.7%). We
      showed that serious bias in questionnaires can be revealed by Bland-Altman plots
      but may remain undetected by correlation coefficients. With our simulations we
      refuted the argument that correlation coefficients properly investigate whether a
      questionnaire ranks the subjects sufficiently well. Further, with Bland-Altman
      analyses we could evaluate differential errors with respect to case-control
      status in our validation study. Yet, this was not possible with correlation
      coefficients, because they generally do not identify systematic bias. In
      addition, we show a potential pitfall in the interpretation of Bland-Altman plots
      that might occur in specific rare instances. CONCLUSIONS: The commonly used
      correlation approach can yield misleading conclusions in validation studies. A
      more frequent and proper use of the Bland-Altman methods would be desirable to
      improve epidemiological data quality.

PMID- 16964358
TI  - Markov models for repeated ordinal data.
AB  - OBJECTIVES: To demonstrate the application of Markov models, especially for
      ordinal outcomes, within the context of regression models for correlated data.
      METHODS: A brief review of regression methods for correlated data is given. A
      proportional odds model and a continuation ratio model is applied to repeated
      measurements of macular pigment density, obtained in an intervention study on the
      supplementation of macular carotenoids. The correlation between repeated
      assessments is assumed to follow a first-order Markov model. The models are
      implemented with standard statistical software. RESULTS: Both models, though not
      directly comparable, provide a similar conclusion. The application of these
      models with standard statistical software is straightforward. CONCLUSIONS: Markov
      models can be valuable alternatives to random effects modes or procedures based
      on generalized estimation equations.

PMID- 16964359
TI  - Practical considerations on the use of extreme sib-pairs for obesity.
AB  - OBJECTIVES: The extreme sib-pair approach has been shown to be a powerful
      strategy to identify susceptibility loci linked to quantitative traits. The body
      mass index is the usually assessed trait in genetic studies on human obesity.
      Environmental factors clearly play an important role for this trait. We
      hypothesized that the low weight of most sibs who were seemingly discordant to
      the obese index proband was influenced by other environmental and/or genetic
      factors like restrained eating or psychiatric disorders. METHODS: A screening
      questionnaire was sent to parents of all consecutively admitted patients three
      weeks prior to referral of index probands for inpatient treatment of obesity. The
      first 320 families were further investigated. Twenty-seven seemingly extremely
      discordant sib-pairs (ED) were identified and examined in detail. RESULTS: The
      low weight of most sibs who were seemingly discordant to the obese index proband
      was influenced by factors like restrained eating or psychiatric disorders. Only
      20% of the interviewed ED could be considered as genuine ED. CONCLUSION: We
      conclude that extensive medical evaluation is necessary if the aim is to
      guarantee genuine ED in family studies for human obesity. Non-paternity deserves
      specific attention in ED studies.

PMID- 16964360
TI  - Are KISS data representative of German intensive care units? Statistical issues.
AB  - OBJECTIVES: Data collected within the German nosocomial infection surveillance
      system KISS are recommended as reference data for judging nosocomial infection
      rates in German intensive care units (ICUs). It is unknown whether the KISS data
      tend to under- or overestimate the true infection incidence rates. In this
      article, methodological aspects of the SIR1 study on the incidence of nosocomial
      infections are discussed, with the aim of estimating unbiased incidence rates of
      nosocomial infections in interdisciplinary German ICUs and examining whether the
      KISS data are representative. METHODS: We discuss the following methodological
      issues: 1) Sample size estimation. 2) Stratified random sampling of German ICUs.
      3) Investigation of seasonal effects. 4) Statistical modeling of incidence rates
      using a negative binomial regression model. 5) Comparison of weighted incidence
      rates with the standardized rate ratio (SRR). RESULTS: Random sampling proved
      difficult to realize in practice since many ICUs refused to participate,
      particularly those in small hospitals. Analysis was adjusted for hospital size.
      No seasonal trends were found in the KISS data. Due to marked differences between
      ICUs, the number of infections is over-dispersed compared to a Poisson model, so
      negative binomial regression was used. Fifty ICUs were observed for two
      consecutive months each, corresponding to 21,832 patient days, during which 262
      infections occurred. Infections were more frequent in large hospitals. The
      incidence rates provided by the SIR study are on average (SRR) 1.89 (1.63-2.20)
      times as large as those estimated by the KISS system. CONCLUSION: For estimating
      nosocomial infection incidence rates, random sampling and statistical modeling of
      over-dispersion were successfully performed. The study provides evidence that the
      KISS surveillance system tends to underestimate the true incidence rates of
      nosocomial infections in German ICUs.

PMID- 16964361
TI  - Independence estimating equations for controlled clinical trials with small
      sample sizes--interval estimation.
AB  - OBJECTIVES: The application of independence estimating equations (IEE) for
      controlled clinical trials (CCTs) has recently been discussed, and
      recommendations for its use have been derived for testing hypotheses. The robust
      estimator of variance has been shown to be liberal for small sample sizes.
      Therefore a series of modifications has been proposed. In this paper we
      systematically compare confidence intervals (CIs) proposed in the literature for
      situations that are common in CCTs. METHODS: Using Monte-Carlo simulation
      studies, we compared the coverage probabilities of CIs and non-convergence
      probabilities for the parameters of the mean structure for small samples using
      modifications of the variance estimator proposed by Mancl and de Rouen [7], Morel
      et al. [8] and Pan [3]. RESULTS: None of the proposed modifications behave well
      in each investigated situation. For parallel group designs with repeated
      measurements and binary response the method proposed by Pan maintains the nominal
      level. We observed non-convergence of the IEE algorithm in up to 10% of the
      replicates depending on response probabilities in the treatment groups. For
      comparing slopes with continuous responses, the approach of Morel et al. can be
      recommended. CONCLUSIONS: Results of non-convergence probabilities show that IEE
      should not be used in parallel group designs with binary endpoints and response
      probabilities close to 0 or 1. Modifications of the robust variance estimator
      should be used for sample sizes up to 100 clusters for CI estimation.

PMID- 16964362
TI  - A note on testing for intervention effects on binary responses.
AB  - OBJECTIVES: In some circumstances controlled trials are not feasible and
      treatments can only be evaluated using clinical databases. Here we consider the
      situation where treatment is introduced at a particular calendar time and can
      only be evaluated by comparison with historical controls. In these circumstances
      Heuer and Abel recommended using change-point methods to search for change in
      characteristics over the whole study period rather than simply comparing treated
      and untreated patients. Their recommendation is to only conclude that the
      intervention had an effect if a change-point could be demonstrated close in time
      to the introduction of the new treatment. This reduces the risk of false
      positives caused by confounding changes in population characteristics or changes
      in patient management. For binary data we develop a method that follows their
      philosophy and apply it to an observational study in the treatment of pin sites
      after orthopaedic surgery. METHODS: Tests for change in binomial probabilities
      based on Brownian bridge and Hansen's approximation for maximally selected chi(2)
      statistics are compared to an exact test by Worsley. The approximate method is
      generalized to logistic regression models allowing for covariates. RESULTS: The
      agreement of the exact and approximate method is good for sample sizes of 100 or
      more. The actual test size of the Hansen approximate test allowing for covariates
      is close to the nominal level, whereas the Brownian bridge approximation is
      slightly conservative. The change in pin site treatment significantly reduces the
      risk of infection for both adults and children. CONCLUSIONS: We consider the
      Hansen approximation to provide a very good and very simple method for obtaining
      the p-value when testing for a change in binary data event probabilities, with or
      without covariates.

PMID- 16964363
TI  - Extended cooperation in clinical studies through exchange of CDISC metadata
      between different study software solutions.
AB  - OBJECTIVES: Our objectives were to analyze the possibility of an exchange of an
      entire clinical study between two different and independent study software
      solutions. The question addressed was whether a software-independent transfer of
      study metadata can be performed without programming efforts and with software
      routinely used for clinical research. METHODS: Study metadata was transferred
      with ODM standard (CDISC). Study software systems employed were MACRO (InferMed)
      and XTrial (XClinical). For the Proof of Concept, a test study was created with
      MACRO and exported as ODM. For modification and validation of the ODM export file
      XML-Spy (Altova) and ODM-Checker (XML4Pharma) were used. RESULTS: Through
      exchange of a complete clinical study between two different study software
      solutions, a Proof of Concept of the technical feasibility of a system
      independent metadata exchange was conducted successfully. The interchange of
      study metadata between two different systems at different centers was performed
      with minimal expenditure. A small number of mistakes had to be corrected in order
      to generate a syntactically correct ODM file and a "vendor extension" had to be
      inserted. After these modifications, XTrial exhibited the study, including all
      data fields, correctly. However, the optical appearance of both CRFs (case report
      forms) was different. CONCLUSIONS: ODM can be used as an exchange format for
      clinical studies between different study software. Thus, new forms of cooperation
      through exchange of metadata seem possible, for example the joint creation of
      electronic study protocols or CRFs at different research centers. Although the
      ODM standard represents a clinical study completely, it contains no information
      about the representation of data fields in CRFs.

PMID- 16964364
TI  - Computed critiquing integrated into daily clinical practice affects physicians'
      behavior--a randomized clinical trial with AsthmaCritic.
AB  - OBJECTIVE: We developed AsthmaCritic, a non-inquisitive critiquing system
      integrated with the general practitioners' electronic medical records. The system
      is based on the guidelines for asthma and chronic obstructive pulmonary disease
      (COPD) as issued by the Dutch College of General Practitioners. This paper
      assesses the effect of AsthmaCritic on monitoring and treatment of asthma and
      COPD by Dutch general practitioners in daily practice. METHODS: A randomized
      clinical trial in 32 practices (40 Dutch general practitioners) using electronic
      patient records. An intervention group was given the use of AsthmaCritic, a
      control group continued working in the usual manner. Both groups had the disposal
      of the asthma and COPD guidelines routinely distributed by the Dutch College of
      General Practitioners. We measured the average number of contacts, FEV 1 (forced
      expiratory volume), and peak-flow measurements per asthma/COPD patient per
      practice; and, the average number of antihistamine, cromoglycate, deptropine, and
      oral bronchodilator prescriptions per asthma/COPD patient per practice. RESULTS:
      The number of contacts increased in the age group of 12-39 years. The number of
      FEV1 , peak-flow measurements, and the ratio of coded measurements increased,
      whereas the number of cromoglycate prescriptions decreased in the age group of 12
      39 years. CONCLUSIONS: Our study shows that the guideline-based critiquing system
      AsthmaCritic changed the manner in which the physicians monitored their patients
      and, to a lesser extent, their treatment behavior. In addition, the physicians
      changed their data-recording habits.

PMID- 16964365
TI  - The "resident's dilemma"? Values and strategies of medical residents for
      education interactions: a cellular automata simulation.
AB  - OBJECTIVES: Medical residents engage in formal and informal education
      interactions with fellow residents during the working day, and can choose whether
      to spend time and effort on such interactions. Time and effort spent on such
      interactions can bring learning and personal satisfaction to residents, but may
      also delay completion of clinical work. METHODS: Using hypothetical cases, we
      assessed the values and strategies of internal medicine residents at one hospital
      for both cooperative and non-cooperative education interactions with fellow
      residents. We then used these data and cellular automata models of two-person
      games to simulate repeated interactions between residents, and to determine which
      strategies resulted in greatest accrued value. We conducted sensitivity analyses
      on several model parameters, to test the robustness of dominant strategies to
      model assumptions. RESULTS: Twenty-nine of the 57 residents (50.9%) valued
      cooperation more than non-cooperation no matter what the other resident did
      during the current interaction. Similarly, thirty-six residents (63.2%) endorsed
      an unconditional always-cooperate strategy no matter what the other resident had
      done during their previous interaction. In simulations, an always-cooperate
      strategy accrued more value (776.42 value units) than an aggregate of strategies
      containing non-cooperation components (675.0 value units, p = 0.052). Only when
      the probability of strategy errors reached 50%, or when values were re-ordered to
      match those of a Prisoner's Dilemma, did non-cooperation-based strategies accrue
      the most value. CONCLUSIONS: Cooperation-based values and strategies were most
      frequent among our residents, and dominated in simulations of repeated education
      interactions between them.

PMID- 16964366
TI  - A modified method of activity-based costing for objectively reducing cost drivers
      in hospitals.
AB  - OBJECTIVES: Activity-based costing (ABC) is widely used to precisely allocate
      indirect costs to medical services. In the ABC method, the indirect cost is
      divided among the medical services in proportion to the volume of "cost drivers",
      for example, labor hours and the number of hours of surgery. However, the
      workload of data collection of cost drivers can be time-consuming and a
      considerable burden if there are many cost drivers. The authors aim to develop a
      method for objectively reducing the cost drivers used in the ABC method. METHODS:
      In the ABC method, the cost driver is assigned for each activity. We assume that
      these activities and cost drivers are the best combination. Our method, that is
      cost driver reduction (CDR), can objectively select surrogates of the cost
      drivers for each activity in ABC from candidate cost drivers. Concretely, the
      total indirect cost of an activity is temporarily allocated to the medical
      services using each candidate of cost drivers. The difference between the costs
      calculated by each candidate and the proper cost driver used in ABC is calculated
      to evaluate the similarity by the evaluation function. RESULTS: We estimated the
      cost of laboratory tests using our method and revealed that the number of cost
      drivers could be reduced from seven in the ABC to four. Similarly, the results of
      cost estimation obtained by our method were as accurate as those calculated using
      the ABC. CONCLUSIONS: Our method provides two advantages compared to the ABC
      method: 1) it provides results that are as accurate as those of the ABC method,
      and 2) it is simpler to perform complicated estimation of hospital costs.

PMID- 16964367
TI  - Guidance of neural crest cell migration: the inhibitory function of the
      chondroitin sulfate proteoglycan, versican.
AB  - Neural crest cells are specialized multipotent embryonic stem cells found
      exclusively in vertebrates[1,2,3]. During embryonic development, these cells
      arise from the dorsal neural tube, undergo epithelial to mesenchymal transition,
      and subsequently migrate along stereotyped pathways to reach specific tissue
      targets, where they differentiate into a wide variety of cell types, such as glia
      and neurons of the peripheral nervous system, melanocytes, smooth muscle cells,
      craniofacial cartilage and bone tissues, or chromaffin cells of the adrenal
      medulla. In the trunk region, the ventrally migrating neural crest cells move
      through the somitic mesenchyme in a segmented pattern, presumably setting the
      basis for the metameric organization of sensory and sympathetic ganglia along the
      anterior-posterior axis later in development[4].

PMID- 16964368
TI  - The limited role of microbiological culture and sensitivity in the management of
      superficial soft tissue abscesses.
AB  - The aim of this study was to assess the role of the routine practice of microbial
      culture and sensitivity at incision and drainage of superficial soft tissue
      abscesses. The case notes of 162 consecutive patients, selected from the
      microbiology database over a period of 1 year, were reviewed. All had incision
      and drainage of superficial soft tissue abscesses and included perianal,
      pilonidal, axillary, and breast abscesses. Patients with chronic wounds,
      recurrent abscesses, diabetes, pregnancy, and immunosuppression were excluded.
      The impact of pus culture and sensitivity (C/S) on management and clinical
      outcome was documented. Out of 162 patients, 97 were male (59.8%) and 65 were
      female (40.1%). Only 115 (70.9%) yielded positive cultures and 47 (29.1%) were
      sterile. The cultured microbial flora was predictable and sensitive to empirical
      antibiotics. In four patients, the results of microbial culture sensitivity
      showed microbial resistance to empirical antibiotics; however, it did not affect
      the management or the outcome for these patients. The routine practice of sending
      swabs for C/S after incision and drainage of superficial soft tissue abscesses
      does not contribute significantly towards patient management. Most patients are
      already on antibiotics prior to the referral and in the remainder, surgeons start
      antibiotics empirically. These broad-spectrum antibiotics cover the common
      pathogens involved, and there is no significant change in the antibiotic
      treatment after reviewing the culture reports following incision and drainage of
      uncomplicated superficial skin abscesses.

PMID- 16964369
TI  - An intensified esterification process of palm oil fatty acid distillate catalyzed
      by delipidated rice bran lipase.
AB  - An intensified esterification process was operated by circulating 10 l of
      reaction mixtures, consisting of palm oil fatty acid distillate (PFAD) and
      glycerol in hexane, through a packed-bed reactor (PBR) filled with 10 kg of
      delipidated rice bran lipase (RBL). The influence of the process parameters, such
      as reaction temperature and type of water-removal agent, on the performance of
      this intensified esterification process were investigated. The highest degree of
      esterification (61%) was achieved at a reaction temperature of 65 masculineC,
      using silica gels as the water-removal agent. Thin-layer chromatography (TLC)
      analysis showed that the major composition of the esterified product was
      diacylglycerol.

PMID- 16964370
TI  - Human development IV: the living cell has information-directed self-organisation.
AB  - In this paper, restricted to describe the ontogenesis of the cell, we discuss the
      processing of DNA through RNA to proteins and argue that this process is not able
      to transfer the information necessary to organize the proteins in the cell, but
      only to transfer the information necessary to form the shape of the proteins. We
      shortly describe the structure of the information carrying field recruited by the
      cells that we think is responsible for building the organelles and other cellular
      structures. We use the cells superior control of its cytoskeleton as an example
      of how the cell is using an informational field giving the positional information
      guiding all the local chemical processes behind the cell movement. We describe
      the information-directed self-organization in cells and argue that this can
      explain the ontogenesis of the cell. We also suggest the existence of an
      undiscovered phenomenon behind the information transmitting cell interactions. We
      conclude that during evolution the cell has developed into an information-guided
      self-organizing structure. The mystery we want to solve is: what is the
      mechanical cause and nature of biological information?

PMID- 16964371
TI  - Diaphragm disease: the limitation of laparoscopy and assessment of the small
      bowel for strictures using a ball bearing.
AB  - Diaphragm disease is a rare cause of intestinal obstruction that will be seen
      with increasing frequency with the widespread use of nonsteroidal anti
      inflammatory drugs (NSAIDs). We present a case study of a patient with diaphragm
      disease where the diagnosis was not apparent at laparoscopy, and passage of a
      steel ball through the small intestine was required to identify all strictures
      present. A high index of suspicion, recognition of the limitations of
      conventional diagnostic aids, and the need to assess the full length of the small
      bowel are all important in the surgical management of this condition.

PMID- 16964372
TI  - Understanding tobacco smoke carcinogen NNK and lung tumorigenesis.
AB  - The deleterious effects of tumor-promoting tobacco carcinogen, nitrosamine 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, nicotine-derived nitrosamine
      ketone) have undoubtedly been stipulated. Though many tobacco agents play a part
      in the development of lung tumors, the potent effects of NNK remain unmatched. It
      is therefore critical to distinguish the variety of cofactors involved in NNK
      mediated pathogenesis, and the unique pathways necessary for successful cellular
      biotransformation. Current reviews have consistently identified the strengths of
      NNK and prospective tumor capabilities. Others have delineated specific cellular
      factors mediating NNK and lung tumors, and have identified metabolic and
      signaling pathways largely responsible for NNK activation and tumorigenic
      initiation. Unique to this review is that it summarizes the extensive network of
      cofactors and cellular mechanisms that promote NNK-specific lung tumorigenesis.
      As such, it displays a fuller, more comprehensive overview, bringing us one step
      closer to understanding the fatal consequences of NNK, thus, discovering new
      avenues that successfully break the cycle of NNK-mediated lung carcinogenesis.

PMID- 16964373
TI  - Chromosomal end fusion resulting from telomere erosion increases susceptibility
      to radiation via multinucleation: effect of p53.
AB  - Loss of p53 tumor suppressor facilitates acquisition of telomerase activity. In
      fact, both p53 inactivation and telomerase activation are frequently found in
      human cancers. p53 inactivation, however, eliminates or attenuates the biological
      responses to telomerase inhibition and the eventual telomere erosion. We show
      that telomere erosion can increase the susceptibility to radiation, irrespective
      of p53 status. Both telomerase inhibition and critically shortened telomere with
      significant change of chromosomal end-to-end fusion were essential for the
      enhancement of radiosensitivity. The enhancement was correlated with greater
      formation of multinucleated cells. p53 inactivation did not eliminate the
      observed generation of chromosomal fusion and multinucleation, and the resulting
      increased susceptibility to radiation, as opposed to the previously proved role
      of p53 in mediating cellular responses to telomere dysfunction. The present
      findings suggest the importance of chromosomal end fusion in modulating
      radiosensitivity rather than p53 DNA damage signaling. Thus, the suggested
      anticancer radiotherapeutic strategy combined with telomerase inhibition could
      clinically be applicable to cancers, irrespective of p53 status.

PMID- 16964374
TI  - Evidence accumulating in support of cancer vaccines combined with chemotherapy: a
      pragmatic review of past and present efforts.
AB  - In the early 1970s supervised clinical trials were initiated at The University of
      Texas M.D. Anderson Hospital in Houston, TX, for the combination of viral
      oncolysate-based vaccines and contemporary chemotherapy for the treatment of
      patients with metastatic melanoma and sarcomas. This therapeutic approach was
      then generally considered to be inappropriate based on a widely held belief that
      the efficacy of cancer vaccines would be negated by the immunosuppressive effects
      of the chemotherapy. Not NCI grants, but institutional funds supported these
      clinical trials. These early clinical trials included in vitro tests for anti
      tumor cell antibodies and cytotoxic lymphocytes both in autologous and allogeneic
      settings and showed that these faculties remained active even after chemotherapy.
      The contemporary reports of unexpectedly favorable clinical results are recited
      in this article. Despite these most promising results, support from federal
      granting agencies (the NIH/NCI) was repeatedly denied; these denials were based
      on the prevailing dogma that the two treatment modalities are expected to be
      antagonistic and not synergistic or not even additive. However, thirty years
      later, now in the new era of molecular medicine, a rapidly increasing number of
      peer-reviewed publications appear and offer convincing evidence that strongly
      substantiate the therapeutic value of combined cancer chemoimmunotherapy. The
      important provision is that the sequencing and dosing of the two major treatment
      modalities, the vaccination and the chemotherapy, are to be pre-tested and then
      the methodology is to be adhered to in the new clinical trials. New sophisticated
      experiments carried out in vitro and in vivo and subsequent clinical trials
      attest to the potential value of this combinatory approach and explain the
      underlying molecular mechanisms. This pragmatic review recapitulates the
      empirically administered earliest clinical trials, and lists and interprets, in
      view of their molecular immunomodulatory effects, the exemplary new clinical
      trials.

PMID- 16964375
TI  - Expression status of RUNX1/AML1 in normal gastric epithelium and its mutational
      analysis in microdissected gastric cancer cells.
AB  - Although Runt-related transcription factors RUNXs (RUNX1-3) have a high
      similarity in their structure, only RUNX3 is known to be involved in gastric
      carcinogenesis. First, we examined mRNA expression of these three RUNX genes in
      the gastric mucosa, and, finding only RUNX2 was not expressed there, we further
      investigated RUNX1 and RUNX3 expression in three regions including the pit,
      isthmus/neck, and gland regions of the human normal stomach and whether RUNX1 is
      involved in gastric carcinogenesis. The mRNA expression of RUNX1 and RUNX3 was
      examined by use of the three regions isolated by laser-captured microdissection
      (LCM) and by use of primary gastric cancer tissues. Furthermore, RUNX1 mutational
      analysis was performed in the cancer cells, which also were isolated from 44
      paraffin-embedded gastric cancer tissues by LCM. RUNX1 was co-expressed with
      RUNX3 in the pit region, and has cell growth-inhibition activity similar to
      RUNX3. RUNX3 has been reported to be suppressed by DNA methylation in a subset of
      gastric cancers; however, the expression of RUNX1 mRNA was observed in all of the
      gastric cancer cell lines and gastric cancer tissues that we examined. No RUNX1
      mutation was found in the 44 gastric cancer patients. Although RUNX1 is similar
      to RUNX3 in both the expression pattern in the stomach and its cell growth
      inhibition activity, RUNX1 is not involved in most cases of gastric cancers.
      These results suggest that the transcriptional target genes are different between
      these two family genes.

PMID- 16964376
TI  - A single cycle of treatment with temozolomide, alone or combined with O(6)
      benzylguanine, induces strong chemoresistance in melanoma cell clones in vitro:
      role of O(6)-methylguanine-DNA methyltransferase and the mismatch repair system.
AB  - Clinically achievable concentrations of temozolomide (TMZ) produce cytotoxic
      effects only in mismatch repair (MMR)-proficient cells endowed with low O6
      methylguanine-DNA methyltransferase (MGMT) activity. Aim of the present study was
      to investigate the molecular mechanisms underlying acquired resistance of
      melanoma cells to TMZ and the effect of O6-benzylguanine (BG), a specific MGMT
      inhibitor, on the development of a TMZ-resistant phenotype. Three MMR-proficient
      melanoma cell clones with low or no MGMT activity were treated daily for 5 days
      with 50 micromol/l TMZ, alone or in combination with 5 micromol/l BG. Parental
      clones and sublines established after one or four cycles of treatment were
      analyzed for sensitivity to TMZ or TMZ+BG and for other parameters. The sublines
      established after one cycle of TMZ or TMZ+BG exhibited a marked increase in MGMT
      activity and resistance to TMZ alone. BG only partially reversed acquired
      resistance to the drug. In some cases, alterations in the MMR system accounted
      for MGMT-independent resistance to TMZ. Up-regulation of MGMT activity was
      associated with either demethylation of the MGMT promoter or hypermethylation of
      the body of the gene, and partially reversed by 5-aza-2'-deoxycytidine. The
      sublines established after four cycles of TMZ or TMZ+BG did not show a further
      increase in resistance to TMZ alone. However, two out of three sublines
      established after TMZ+BG treatment exhibited increased resistance to TMZ+BG. In
      conclusion, our data demonstrate that a single cycle of TMZ is sufficient to
      induce high levels of drug resistance in melanoma clones, principally, but not
      exclusively, via up-regulation of MGMT expression. Exposure to TMZ+BG favors the
      development of MGMT-independent mechanisms of TMZ resistance.

PMID- 16964377
TI  - Genome-wide gene expression profiles of clear cell renal cell carcinoma:
      identification of molecular targets for treatment of renal cell carcinoma.
AB  - In order to clarify the molecular mechanism involved in renal carcinogenesis, and
      to identify molecular targets for diagnosis and treatment, we analyzed genome
      wide gene expression profiles of 15 surgical specimens of clear cell renal cell
      carcinoma (RCC), compared to normal renal cortex, using a combination of laser
      microbeam microdissection (LMM) with a cDNA microarray representing 27,648 genes.
      We identified 257 genes that were commonly up-regulated and 721 genes that were
      down-regulated in RCCs. None of top 24 up-regulated genes that showed most
      significant differences in informative RCC-cases were included in previous
      reports describing expression profiles of RCC using RNAs isolated from bulk
      tissues. These findings suggest that it is important to purify as much as
      possible the populations of cancerous and normal epithelial cells obtained from
      surgical specimens. Among the significantly-transactivated genes, we focused on
      Semaphorin 5B (SEMA5B) and knocked-down its expression in RCC cells by small
      interfering RNA (siRNA). Effective down-regulation of its expression levels in
      RCC cells significantly attenuated RCC cell viability. In conclusion, our data
      should be helpful for a better understanding of the tumorigenesis of RCC and
      should contribute to the development of diagnostic tumor markers and molecular
      targeting therapy for patients with RCC.

PMID- 16964378
TI  - Aldo-keto reductase 1 family B7 is the gene induced in response to oxidative
      stress in the livers of Long-Evans Cinnamon rats.
AB  - The Long-Evans Cinnamon (LEC) rat strain (Atp7b m/m), which accumulates copper in
      the liver due to mutations in the Atp7b gene, is a useful model for investigating
      the relationship between oxidative stress and hepatocarcinogenesis. To determine
      the effect of this mutation on oxidative stress marker genes, we performed
      oligonucleotide array analysis (Affymetrix), and compared the results in Atp7b
      m/m rats with those of a sibling line with the Atp7b w/w genotype. We focused our
      studies on the expression of the aldo-keto reductase 1 family B7 (AKR1B7)-like
      protein gene, since this gene codes for reductase enzymes involved in the
      detoxification of oxidizing compounds (e.g., aldehydes) and was differentially
      expressed in Atp7b m/m and Atp7b w/w rat liver. Akr1B7 mRNA expression was
      significantly increased in comparison with the expression of 4 other known
      oxidative stress responsive genes, haem-oxygenase-1 (HO-1), thioredoxin (Trx),
      aldehyde reductase (AKR1A1), and glucose-6-phosphate dehydrogenase (G6PDH). By
      searching binding motifs, five nuclear factor kappa B (NF-kappaB) binding sites
      were located in the 5'-upstream region of the akr1b7 gene. Transient co
      transfection with both I-kappaBalpha and the Akr1b7 6 kb promoter (p6.0-AKR-Luc)
      inhibited luciferase activity of p6.0-AKR-Luc in HepG2 cells. Cuprous ion however
      did not affect the transcription activity induced by p6.0-AKR-luc. Gel-shift
      assay showed that the DNA binding activity of NF-kappaB increased in the livers
      of LEC rats, suggesting that the oxidative stress is mediated through NF-kappaB.
      The results indicate conclusively that in LEC rat liver, akr1b7 might be up
      regulated by oxidative stress mediated through NF-kappaB, but not that mediated
      directly by copper.

PMID- 16964379
TI  - Regulation of ERK3/MAPK6 expression by BRAF.
AB  - Several forms of cancer are characterized by frequent activating mutations in the
      serine/threonine kinase, BRAF. Substitution of glutamic acid for valine at codon
      600 (V600E) accounts for approximately 90% of all BRAF activating mutations and
      leads to stimulation of kinase activity, downstream signaling, and cell
      transformation. To better understand the molecular pathogenesis induced by
      oncogenic BRAF signaling, we used microarray gene expression profiling to
      comprehensively analyze the BRAF-directed transcriptional program of cells
      expressing a conditionally active form of BRAFV600E. Several novel genes that
      affect proliferation, cell survival, angiogenesis and immune surveillance were
      identified as possible mediators of BRAF-induced oncogenic signaling. Moreover,
      we show that a MAPK family member, extracellular signal-regulated kinase-3
      (ERK3/MAPK6) is highly expressed in response to BRAF signaling in this system.
      Cellular ERK3 protein is highly unstable and pharmacological inhibition of BRAF
      activity resulted in rapid ERK3 degradation. In melanoma cells, RNAi-mediated
      knockdown of endogenous BRAF or treatment with MEK inhibitors that prevent ERK1/2
      activation led to a reduction in ERK3 levels, indicating that elevated ERK3
      expression is mediated through MEK1/2 signaling. These results provide strong
      evidence for another mode by which BRAF can regulate the ERK protein kinase
      family and suggest ERK3 to be a potential pharmacodynamic marker for targeting
      BRAF signaling in melanoma.

PMID- 16964380
TI  - KIT/stem cell factor expression in premalignant and malignant lesions of the
      colon mucosa in relationship to disease progression and outcomes.
AB  - Autocrine/paracrine stimulation of KIT has been observed in colorectal carcinoma
      (CRC) cell lines. We investigated the expression of KIT and stem cell factor
      (SCF) in CRC in comparison with premalignant colon lesions and normal colonic
      mucosa to assess the prognostic and therapeutic relevance of this receptor/ligand
      system in CRC. Transcript levels of c-kit and the two SCF splicing variants were
      determined quantitatively by real-time RT-PCR using cDNA obtained from normal,
      premalignant and malignant snap frozen colon tissue specimens.
      Immunohistochemistry with specific anti-KIT and anti-SCF antibodies was performed
      on paraffin-embedded tissue sections in order to localize the relative protein
      expression in epithelial compartments. Approximately 10% of patients expressed
      KIT in their adenoma or primary tumor. The majority of KIT-positive carcinomas co
      expressed SCF. Real-time RT-PCR showed expression of c-kit and SCF transcripts in
      all cDNA specimens examined. A significant association between the co-expression
      of KIT/SCF and a worse clinical outcome was found. In conclusion, KIT expression
      was observed in a proportion of premalignant and malignant colonic lesions, while
      it was virtually absent in normal colon mucosa. Moreover, the majority of KIT
      positive carcinomas co-expressed SCF, suggesting the possibility of aberrant
      signaling by an autocrine loop, as confirmed by the negative prognostic value of
      this association. Therefore, in the subset of CRC patients with concomitant
      KIT/SCF expression, the activity of Imatinib mesylate, a selective inhibitor of
      specific tyrosine kinases including KIT, may be exploited in combination with
      standard therapy.

PMID- 16964381
TI  - Interaction and stabilization of X-linked inhibitor of apoptosis by Raf-1 protein
      kinase.
AB  - Raf-1 serine/threonine protein kinase plays an important role in cell growth,
      differentiation and cell survival. Recent reports using c-raf-1 gene-knockouts
      have observed MEK/ERK independent functions of Raf-1 in cell survival and
      protection from apoptosis. Raf-1 has also been shown to be involved in
      counteracting specific apoptotic pathways by restraining caspase activation,
      although the precise mechanism is unknown. XIAP is a potent inhibitor of
      apoptosis that blocks both the mitochondria and death receptor mediated pathways
      of apoptosis by directly binding to and inhibiting the initiator and effector
      caspases. In our efforts to understand the mechanism by which Raf-1 inhibits
      caspase activation, we discovered a novel interaction between Raf-1 and XIAP. In
      this study, we describe the physical interaction between Raf-1 and XIAP in vitro
      and in vivo in mammalian cells. We also demonstrate that Raf-1 phosphorylates
      XIAP in vitro and in vivo. Additionally, Raf-1 prevents XIAP degradation in
      response to different apoptotic triggers. Our studies identify XIAP as a new
      substrate of Raf-1 and provide potentially important insight into mechanisms
      underlying Raf-1 effects on cell survival.

PMID- 16964382
TI  - Expression of interleukin (IL)-11 and IL-11 receptor in human colorectal
      adenocarcinoma: IL-11 up-regulation of the invasive and proliferative activity of
      human colorectal carcinoma cells.
AB  - Previous investigations have shown that interleukin (IL)-11/IL-11 receptor alpha
      chain (IL-11Ralpha), a member of the PI3K, MAPK and JAK-STAT activating family of
      cytokines/receptors, correlates with the regulation of tumor progression. In this
      study, we established the IL-11/IL-11Ralpha expression profile in human
      colorectal adenocarcinoma (CRC) and clarified its signaling pathway and role in
      the invasion activity of CRC cell lines. To elucidate the role of IL-11/IL
      11Ralpha, we examined 103 cases of CRC and 24 cases of colorectal adenoma by
      immunohistochemistry. In addition, we investigated the invasive activity of cell
      signaling pathway of CRC cell lines. The IL-11Ralpha expression was correlated
      with tumor invasion and lymphatic infiltration (p<0.01, respectively).
      Recombinant human IL-11 (rhIL-11) promoted the migration and proliferation of HT
      29 cells and activated the PI3K and p44/p42 MAPK pathways. Wortmannin, a PI3K
      inhibitor, and PD98059, a p44/p42 MAPK inhibitor, significantly reduced the
      promotion of invasion and proliferation activity by rhIL-11, respectively. In
      summary, the IL-11Ralpha expression was correlated with clinicopathological
      features and IL-11 promoted the invasion via the PI3K and up-regulated the
      proliferation via the p44/p42 MAPK in CRC cells. These findings suggested that
      the IL-11/IL-11R pathway plays an important role in the progression of CRC.

PMID- 16964383
TI  - Detection of chromosomal aberrations by comparative genomic hybridization during
      transformation of human breast epithelial cells in vitro.
AB  - Breast cancer is the most frequent malignancy in women. It is well recognized
      that tumorigenesis is a multistep process resulting from the accumulation of
      sequential genetic alterations. In breast cancers LOH has been described on one
      or both arms of multiple chromosomes. Comparative genomic hybridization (CGH)
      analysis was performed to identify chromosomal imbalances in the breast
      epithelial cells (HBEC). We have used a human in vitro-in vivo system in which
      the environmental carcinogen benz(a)pyrene (BP) and the c-Ha-ras oncogene were
      utilized for inducing in vitro transformation of HBEC. Immortal MCF-10F cells
      were treated with BP which resulted in the transformed cell line BP-1 that was
      further enhanced by transfection with the c-Ha-ras to generate the cell line BP-1
      Tras. This cell line is tumorigenic when injected in severe combined
      immunodeficient (SCID) mice, generating the tumor cell line BP-1-Tras T J#4. Our
      comparative genomic hybridization analysis indicates that the most
      overrepresented segment after cell transformation and in the BP-1, BP-1-Tras and
      in the tumor cell line were 1p (80%), 5q21-ter (80%), 8q24.1 (90%) and Xq27-28
      (60%). DNA sequence amplification at 10p14-15 was observed in BP-1-Tras T J#4
      cells. Allelic losses of chromosome 4, 8p11-21 and 15q11-12, occur after cell
      transformation and are maintained consistently during tumorigenesis.

PMID- 16964384
TI  - Effect of sulforaphane on cell growth, G(0)/G(1) phase cell progression and
      apoptosis in human bladder cancer T24 cells.
AB  - Isothiocyanates (ITCs) from cruciferous vegetables have been shown to be
      effective in blocking initiation as well as progression of a range of chemically
      induced tumors in animal models. In this study, sulforaphane, the most
      extensively studied ITC, was found to suppress the growth of T24 bladder cancer
      cells in vitro in a dose-dependent manner. Sulforaphane inhibited the
      proliferation of T24 cells with IC(5)0 values 26.9 and 15.9 microM following 24
      and 48 h treatments. Sulforaphane (5-20 microM) induced early apoptosis and
      blocked cell cycle progression at G(0)/G(1) phase which was associated with
      upregulation of cyclin-dependent kinase inhibitor p27 expression. These results
      support a role for sulforaphane as an effective agent in the chemoprevention of
      bladder cancer.

PMID- 16964385
TI  - Patterns of p73 N-terminal isoform expression and p53 status have prognostic
      value in gynecological cancers.
AB  - The goal of this study was to determine whether patterns of expression profiles
      of p73 isoforms and of p53 mutational status are useful combinatorial biomarkers
      for predicting outcome in a gynecological cancer cohort. This is the first such
      study using matched tumor/normal tissue pairs from each patient. The median
      follow-up was over two years. The expression of all 5 N-terminal isoforms (TAp73,
      DeltaNp73, DeltaN'p73, Ex2p73 and Ex2/3p73) was measured by real-time RT-PCR and
      p53 status was analyzed by immunohistochemistry. TAp73, DeltaNp73 and DeltaN'p73
      were significantly upregulated in tumors. Surprisingly, their range of
      overexpression was age-dependent, with the highest differences delta (tumor
      normal) in the youngest age group. Correction of this age effect was important in
      further survival correlations. We used all 6 variables (five p73 isoform levels
      plus p53 status) as input into a principal component analysis with Varimax
      rotation (VrPCA) to filter out noise from non-disease related individual
      variability of p73 levels. Rationally selected and individually weighted
      principal components from each patient were then used to train a support vector
      machine (SVM) algorithm to predict clinical outcome. This SVM algorithm was able
      to predict correct outcome in 30 of the 35 patients. We use here a mathematical
      tool for pattern recognition that has been commonly used in e.g. microarray data
      mining and apply it for the first time in a prognostic model. We find that
      PCA/SVM is able to test a clinical hypothesis with robust statistics and show
      that p73 expression profiles and p53 status are useful prognostic biomarkers that
      differentiate patients with good vs. poor prognosis with gynecological cancers.

PMID- 16964386
TI  - OY-TES-1 expression and serum immunoreactivity in epithelial ovarian cancer.
AB  - OY-TES-1 is a novel target that belongs to the family of 'cancer/testis' (CT)
      antigens. Our goal was to examine the expression and immunogenicity of OY-TES-1
      in epithelial ovarian cancer (EOC) to determine its potential as a target for
      vaccine therapy. OY-TES-1 expression was determined by one-step reverse
      transcriptase PCR on 100 EOC samples, 5 EOC cell lines, and a panel of normal
      tissues. Immunohistochemistry (IHC) was performed on the same panel of EOC
      tissues. Sera from a sub-group of patients were tested for OY-TES-1 antibody by
      ELISA. Thymus and leukocytes were weakly positive for OY-TES-1 while the
      remaining 5 normal tissues were negative. Expression of OY-TES-1 by either RT-PCR
      and/or IHC was demonstrable in 69/100 (69%) tumors. Humoral immunity to OY-TES-1
      was demonstrated in 1/10 (10%) serum samples from patients whose tumors expressed
      the antigen. The median follow-up of the patient population was 34 months. There
      was no correlation between antigen expression and stage, grade, histology and
      survival. OY-TES-1 is expressed in 69% of patients with EOC, is absent from
      normal ovarian tissue, and a proportion of patients show evidence of a specific
      humoral immune response. These findings make OY-TES-1 an attractive target for
      antigen-specific immunotherapy in EOC.

PMID- 16964387
TI  - Prevention of melanoma metastases in lungs of BAT treated and peptide immunized
      mice.
AB  - BAT is an immune-modulatory monoclonal antibody that exhibits strong lymphocyte
      mediated anti-tumor activity against a variety of murine and human tumors.
      Peptide A is a vaccine we have developed by screening a phage display peptide
      library on BAT monoclonal antibody. Anti-tumor activity was obtained in mice
      inoculated with B16 melanoma by either a single injection with BAT or
      immunization with peptide A. The aim of this study was to follow and compare
      histopathologically the process of prevention of melanoma metastases in lungs of
      treated and immunized mice. Mice were sacrificed on different days after tumor
      inoculation, their lungs were weighed and the number of metastases was counted.
      The lungs were then fixed in formalin, embedded in paraffin, and stained with
      hematoxylin and eosin. Histological examination of tumor inoculated mice on day
      10 revealed the existence of microscopic melanoma lesions (0.01-0.012 mm) that
      increased gradually in number and size and on day 21, most of the metastases were
      large and spanned entire lobes, from the pleura to the hilum, measuring up to 3.5
      mm and coexisting with scattered, small metastases showing the same morphology
      and pattern of lung involvement. On day 24, the lungs of untreated mice were
      massively infiltrated by coalescing metastases replacing up to 50% of the lung
      tissue and measuring up to 7.0 mm. The number of lung metastases and weight was
      dramatically decreased by a single injection of BAT monoclonal antibody ten days
      post tumor inoculation. The treated mice clearly had fewer and smaller metastases
      in different mice at the different days post tumor inoculation. On day 21, there
      were few small metastases measuring up to 1.6 mm and on day 24 no lung metastases
      were detected in this group that appeared with a completely normal lung
      structure. Immunization with peptide A started one day post tumor inoculation and
      was compared to immunization with control peptide N. Fourteen days post tumor
      inoculation, mice immunized with peptide A had only 1-2 metastases (0.012-0.076
      mm) and on day 24 ranged up to 2 mm compared to control immunized mice where the
      tumor developed up to 5-7 mm. Foci of lung inflammation in both the untreated,
      treated or immunized mice were rare, small, and not preferentially associated
      with the lung metastases. They were composed mainly of small lymphocytes and a
      few macrophages. This study is the basis of histopathological understanding of
      metastases prevention in lungs of mice immunized or treated by BAT monoclonal
      antibody.

PMID- 16964388
TI  - Gene expression patterns of chemoresistant and chemosensitive serous epithelial
      ovarian tumors with possible predictive value in response to initial
      chemotherapy.
AB  - Chemotherapy (CT) resistance in ovarian cancer is broad and encompasses diverse,
      unrelated drugs, suggesting more than one mechanism of resistance. We aimed to
      analyze the gene expression patterns in primary serous epithelial ovarian cancer
      (EOC) samples displaying different responses to first-line CT in an attempt to
      identify specific molecular signatures associated with response to CT. Initially,
      the expression profiles of 15 chemoresistant serous EOC tumors [time to
      recurrence (TTR) </=6 months] and 10 chemosensitive serous EOC tumors (TTR > or
      =30 months) were independently analyzed which allowed the identification of
      specific sets of differentially expressed genes that might be functionally
      implicated in the evolution of the chemoresistant or the chemosensitive
      phenotype. Our data suggest that the intrinsic chemoresistance in serous EOC
      cells may be attributed to the combined action of different molecular mechanisms
      and factors linked with drug influx and efflux and cell proliferation, as
      possible implications of other molecular events including altered metabolism,
      apoptosis and inflammation cannot be excluded. Next, gene expression comparison
      using hierarchical clustering clearly distinguished chemosensitive and
      chemoresistant tumors from the 25 serous EOC samples (training set), and
      consecutive class prediction analysis was used to develop a 43-gene classifier
      that was further validated in an independent cohort of 15 serous EOC patients and
      2 patients with other ovarian cancer histotypes (test set). The 43-gene predictor
      set properly classified serous EOC patients at high risk for early (< or =22
      months) versus late (>22 months) relapse after initial CT. Thus, gene expression
      array technology can effectively classify serous EOC tumors according to CT
      response. The proposed 43-gene model needs further validation.

PMID- 16964389
TI  - Chromosome 22 array-CGH profiling of breast cancer delimited minimal common
      regions of genomic imbalances and revealed frequent intra-tumoral genetic
      heterogeneity.
AB  - Breast cancer is a common malignancy and the second most frequent cause of death
      among women. Our aim was to perform DNA copy number profiling of 22q in breast
      tumors using a methodology which is superior, as compared to the ones applied
      previously. We studied 83 biopsies from 63 tumors obtained from 60 female
      patients. A general conclusion is that multiple distinct patterns of genetic
      aberrations were observed, which included deletion(s) and/or gain(s), ranging in
      size from affecting the whole chromosome to only a few hundred kb. Overall, the
      analysis revealed genomic imbalances of 22q in 22% (14 out of 63) of tumors. The
      predominant profile (11%) was monosomy 22. The smallest identified candidate
      region, in the vicinity of telomere of 22q, encompasses approximately 220 kb and
      was involved in all but one of the tumors with aberrations on chromosome 22. This
      segment is dense in genes and contains 11 confirmed and one predicted gene. The
      availability of multiple biopsies from a single tumor provides an excellent
      opportunity for analysis of possible intra-tumor differences in genetic profiles.
      In 15 tumors we had access to two or three biopsies derived from the same lesion
      and these were studied independently. Four out of 15 (26.6%) tumors displayed
      indications of clonal intra-tumor genotypic differences, which should be viewed
      as a high number, considering that we studied in detail only a single human
      chromosome. Our results open up several avenues for continued genetic research of
      breast cancer.

PMID- 16964390
TI  - Sensitization of human colon adenocarcinoma cells (LoVo) to reactive oxygen
      species by a lysosomotropic compound.
AB  - The in situ formation of cytotoxic metabolites by an enzyme-catalyzed reaction is
      a recent approach in cancer therapy. The present results show that multidrug
      resistant human colon adenocarcinoma cells (LoVo) are significantly more
      sensitive than corresponding wild-type cells to hydrogen peroxide and aldehydes,
      the products of bovine serum amine oxidase (BSAO)-catalyzed oxidation of
      spermine. Pre-treatment of the cells with N1,N4-bis(2,3-butadienyl)-1,4
      butanediamine (MDL 72527), a lysosomotropic compound, sensitized both cell lines
      to the subsequent exposure to spermine metabolites, as was evident from the
      decrease of cell survival by a log unit. The sensitizing effect was greater in
      the case of the multidrug-resistant cell line, an aspect of particular importance
      with respect to potential therapeutic applications of the method, since
      conventional cancer therapy suffers from the development of drug resistance. Cell
      viability was determined using a clonogenic assay. MDL 72527 (at 300 microM)
      produced numerous cytoplasmic vacuoles, presumably of lysosomal origin, after 6-h
      exposure, which decreased in size and number (in the presence of the drug) by 24
      h and had almost disappeared completely at 48 h. Mitochondrial damage, as
      observed by transmission electron microscopy, seemed to correlate better with the
      cytotoxic effects of the treatment than the formation of vacuoles. We suggest
      that the release of lysosomal enzymes into the cytosol by MDL 72527 is the main
      reason for its sensitizing effect. It is known that lysosomotropic compounds,
      which release lysosomal enzymes, produce oxidative stress and apoptosis.

PMID- 16964391
TI  - The balanced induction of K-ras codon 12 and 13 mutations in mucosa differs from
      their ratio in neoplastic tissues.
AB  - The aim of this study was to compare the ratio of K-ras codon 12 and 13 mutations
      in various tissues of colorectal cancer patients. Multiple samples of
      inconspicuous mucosa and a sample of carcinoma tissue were taken from 36
      colorectal cancer patients (group I) and these results were compared with those
      from polyp and carcinoma tissues of another 48 colorectal cancer patients (group
      II). A polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) assay was used to detect the respective point mutations. The results of
      this assay were complemented by sequencing the K-ras mutations. In mucosa tissue,
      the ratio of codon 12 and 13 mutations was nearly equal (0.9:1) whereas the
      respective ratio in tumour tissue showed a strong preponderance of K-ras codon 12
      mutations (14:1, p=0.004). In polyp tissue of patients from group II, the ratio
      was 2.7:1 and that in carcinomas was 19:1 (p=0.053). The prevalence of both types
      of mutation was 14.6% in all mucosa samples, corresponding to 30.6% of group I
      patients. The K-ras mutation rate in carcinoma tissue of the same patients was
      38.9%. Similarly, 33.4% of all polyp and 41.7% of all carcinoma samples from
      group II harboured K-ras codon 12 and/or 13 mutations. Sequencing confirmed 59 of
      60 K-ras codon 12 mutations, but due to the detection limit for sequencing
      (1:10(4)) only 10 of 20 K-ras codon 13 mutations were confirmed. It is concluded
      that after balanced induction K-ras codon 12 mutations increase in frequency
      relative to K-ras codon 13 mutations during tumour progression.

PMID- 16964392
TI  - Helicobacter pylori induces mono-(adenosine 5'-diphosphate)-ribosylation in human
      gastric adenocarcinoma.
AB  - Mono-(adenosine 5'-diphosphate) (ADP)-ribosylation, which transfers an ADP-ribose
      from nicotinamide adenine dinucleotide (NAD) to an acceptor protein, is an
      important post-translational modification of cellular proteins. Several bacterial
      toxins are known to possess the mono-ADP-ribosyltransferase activity to catalyze
      this reaction as a possible pathogenic factor. Therefore, the aim of this study
      was to examine whether H. pylori may also induce mono-ADP-ribosylation in a human
      gastric mucosal protein in association with gastric cancer development. Tumorous
      and adjacent non-tumorous mucosal tissue specimens were obtained from the
      surgically removed stomachs of 5 patients with gastric adenocarcinoma, and then
      were homogenized into cytosolic and membranous fractions. Each homogenate or an
      H. pylori extract was assayed for mono-ADP-ribosylation with [adenylate-(32)P]
      NAD and 3-aminobenzamide, a potent inhibitor of poly-ADP-ribosylation. The
      radiolabeled proteins were separated by sodium dodecylsulfate-polyacrylamide gel
      electrophoresis followed by radio-image analysis. In the extracts from H. pylori,
      a strain-dependent, endogenous radiolabeling of 70-kDa protein was detected. An
      assay of the membranous fractions from 5 gastric adenocarcinomas with the extract
      of OMH4, a clinical H. pylori isolate, revealed notable radiolabelings of 55- and
      45-kDa proteins, which were not found without the OMH4 extract. In contrast, the
      radiolabelings were minimal in the membranous fractions from respective non
      tumorous mucosae, and they were not detected in any of the examined cytosolic
      fractions. All three radiolabelings of 70-, 55-, and 45-kDa proteins were
      dependent on NAD, but not on ADP-ribose. Snake venom phosphodiesterase digestion
      of the 3 radiolabeled proteins released only AMP. We thus found that H. pylori
      had an enzymatic mono-ADP-ribosyltransferase activity which enabled it to modify
      the 55- and 45-kDa membranous proteins of human gastric adenocarcinoma, as well
      as the 70-kDa protein of H. pylori itself. The possible roles underlying our
      observations on carcinogenesis or development of human gastric carcinoma are yet
      to be elucidated.

PMID- 16964393
TI  - Testing for anti-p53 antibodies increases the diagnostic sensitivity of
      conventional tumor markers.
AB  - The aim of this study was to determine whether anti-p53 antibodies are of
      clinical significance as a serological marker in the diagnosis and monitoring of
      malignancies. A total of 1874 serum samples from 591 patients with various types
      of cancer, esophageal, gastric, colorectal, pancreatic, hepatocellular, breast,
      and urogenital cancer, and 436 control individuals were analyzed by immunoblot
      for antibodies against p53. The anti-p53 antibody test was correlated with
      expression of conventional tumor markers, survival and the clinicopathological
      features of malignant disease. Anti-p53 antibodies were found in 23.4% (138/591)
      of the sera of patients with malignant disease (range 11.5-34%). The detection of
      anti-p53 serum antibodies had a specificity of 100% for malignancy (p<0.0001).
      The overall sensitivity of measuring established tumor markers was 62.9%
      (372/591). The elevation of conventional tumor markers and the presence of anti
      p53 antibodies in the sera of patients with malignant disease turned out to be an
      independent variable (p<0.05). Combination of established tumor markers with the
      anti-p53 antibody test led to an increase in diagnostic sensitivity of 8%
      (49/591) (p<0.01). Thus, the independence of anti-p53 antibodies from established
      tumor markers allows the serological detection of additional tumor patients.
      Kaplan-Meier analysis revealed a trend toward a poorer prognosis in
      hepatocellular carcinoma and breast cancer patients who were anti-p53 serum
      positive. In conclusion, testing for anti-p53 antibodies can increase the
      diagnostic sensitivity when used in combination with measurement of conventional
      tumor markers. This increase is achieved without a parallel decrease in
      specificity.

PMID- 16964394
TI  - Activation of p38 MAPK and/or JNK contributes to increased levels of VEGF
      secretion in human malignant glioma cells.
AB  - Malignant gliomas are typically angiogenic and secrete high levels of VEGF.
      Hypoxia has been identified as an important regulator of VEGF. However, malignant
      gliomas express high levels of VEGF in both hypoxic perinecrotic and vital tumor
      areas. In this study, we examined intracellular signaling pathways involved in
      the secretion of VEGF in glioma cells under normoxic conditions. Human malignant
      glioma cell lines, T98G, U373MG, U87MG, and A172, and human fetal lung
      fibroblasts (HFL) were cultured both with and without IL-1beta under normoxic
      conditions. VEGF, IL-1, IL-6, and TNF-alpha were measured with ELISA. VEGF mRNA
      levels were estimated by RT-PCR. Inhibitors of COX-2, MAPK, and phosphatidyl
      inositol 3-kinase (PI3-K), and blocking antibodies to TGF-beta II and TNF-alpha,
      or IL-1 receptor antagonist, were used to examine their effects on VEGF
      secretion. Phosphorylation of MAPK was examined by immunoblotting. The basal
      levels of VEGF secretion were significantly higher in U87MG, U373MG, and T98G,
      than HFL. IL-1beta significantly stimulated VEGF secretion in these glioma cells.
      Inhibitors of p38 MAPK and/or JNK significantly suppressed VEGF secretion both in
      the presence and absence of IL-1beta, while inhibitors of COX-2, ERK1/2, and PI3
      K did not. Constitutive phosphorylation of p38 MAPK and JNK was observed in these
      glioma cells. The levels of IL-1beta in U87MG were significantly higher than in
      other glioma cell lines, and IL-1 receptor antagonist suppressed basal secretion
      of VEGF from U87MG. In conclusion, p38 MAPK and JNK pathways play an important
      role in VEGF secretion from malignant glioma cells under normoxic conditions,
      possibly contributing to VEGF-induced angiogenesis in malignant gliomas at vital
      tumor areas where there is no hypoxia.

PMID- 16964395
TI  - Antiproliferative activity of essential oils derived from plants belonging to the
      Magnoliophyta division.
AB  - The essential oils obtained from different officinal plants of Lebanon, belonging
      to the Magnoliophyta division, have been tested for their antiproliferative
      activity on human erythroleukemic K562 cells. Satureja montana showed the most
      interesting biological activity in inhibiting the cell growth and inducing
      erythroid differentiation of K562 cells. The essential oil of Satureja montana
      was therefore analyzed using a GC/MS (gas chromatography/mass spectrometry)
      system in order to identify the major constituents and compare them with analysis
      performed on Satureja hortensis. We demonstrated that the essential oil
      composition varied with the species, the major constituent of Satureja hortensis
      being carvacrol (50.61%) and that of Satureja montana being alpha-terpineol
      (12.66%). In order to identify molecules possibly responsible for the biological
      activity, commercially available derivatives have been assayed on the K562 cell
      line. Satureja montana essential oil displayed different natural derivatives
      characterized by higher activity than those present in Satureja hortensis. The
      common active principles are alpha-pinene, gamma-terpinene, 4-terpineol, alpha
      terpineol, tau-cadinene, tau-cadinol and caryophyllene. Both caryophyllene and
      alpha-terpineol showed important antiproliferative effects on K562 cells.

PMID- 16964396
TI  - A study comparing endogenous protoporphyrin IX induced by 5-ALA and ALA-methyl
      ester with exogenous PpIX and PpIX dimethyl ester in photodynamic diagnosis of
      human nasopharyngeal carcinoma xenografts.
AB  - 5-Aminolevulinic acid (5-ALA) and its esters have been under intense
      investigation to enhance the endogenous production of protoporphyrin IX (PpIX) in
      tumour cells for the purpose of photodynamic diagnosis. In this study we have
      investigated the use of exogenous PpIX and its dimethyl ester (PME) and compared
      the results with endogenous PpIX produced via 5-ALA and ALA methyl ester (AME) in
      poorly differentiated NPC/CNE-2 nasopharyngeal carcinoma cells in both in vivo
      and in vitro systems. All prodrugs and photosensitizers were administered to
      tumour bearing balb/c nude mice either intravenously or topically. in vitro
      results show that 5-ALA induced more PpIX fluorescence when compared with AME in
      NPC/CNE-2 cells and PME showed better uptake than PpIX. in vivo results show that
      exogenous PpIX and PME show promise as good candidates as photosensitizers for
      photodynamic diagnosis as they exhibit significant selectivity between tumour
      tissue and normal tissue at 3 h. Modification of delivery vehicle used for
      application of exogenous PpIX and PME could allow for rapid uptake; better
      selectivity and localization of the photosensitizer.

PMID- 16964397
TI  - Crosstalk between EGFR and TrkB enhances ovarian cancer cell migration and
      proliferation.
AB  - Ovarian cancer remains the leading cause of fatality among all gynecologic
      cancers, although promising therapies are in the making. It has been speculated
      that metastasis is critical for ovarian cancer, and yet the molecular mechanisms
      of metastasis in ovarian cancer are poorly understood. Growth factors have been
      proven to play important roles in cell migration associated with metastasis, and
      inhibition of growth factor receptors and their distinct cell signaling pathways
      has been intensively studied, and yet the uncovered interaction or crosstalk
      among various growth factor receptors complicates this otherwise promising
      approach. We investigated the crosstalk between EGFR and TrkB, both of which have
      been known to be important in cell survival and migration in response to EGF and
      BDNF. Our results showed that both EGF and BDNF induced cell migration and cell
      proliferation in cultured human ovarian cancer cells (Caov3 cell line). EGF and
      BDNF transactivated TrkB and EGFR respectively, and activated downstream cell
      survival components such as Akt. EGFR and TrkB kinase inhibitors inhibited EGF-
      and BDNF-induced TrkB and EGFR activation and Akt phosphorylation, and cell
      proliferation and migration. Using EGFR knockout cells, we further demonstrated
      that EGFR is required for EGF-induced cell migration. Collectively, our data
      indicate that EGFR and TrkB crosstalk each other in response to EGF and BDNF,
      leading to cell survival pathway activation in ovarian cancer cells. Our data
      suggest that a combination of inhibitors of both receptors with cell survival
      pathway inhibitors would provide a better outcome in the clinical treatment of
      ovarian cancer.

PMID- 16964398
TI  - EG-1 interacts with c-Src and activates its signaling pathway.
AB  - EG-1 is significantly elevated in breast, colorectal, and prostate cancers.
      Overexpression of EG-1 stimulates cellular proliferation, and targeted inhibition
      blocks mouse xenograft tumor growth. To further clarify the function of EG-1, we
      investigated its role in c-Src activation. We observed that EG-1 overexpression
      results in activation of c-Src, but found no evidence that EG-1 is a direct Src
      substrate. EG-1 also binds to other members of the Src family. Furthermore, EG-1
      shows interaction with multiple other SH3- and WW-containing molecules involved
      in various signaling pathways. These observations suggest that EG-1 may be
      involved in signaling pathways including c-Src activation.

PMID- 16964399
TI  - Additive effects of Cox-1 and Cox-2 inhibition on breast cancer in vitro.
AB  - We hypothesized that combined treatment with Cox-1 and Cox-2 specific inhibitiors
      would exhibit synergistic effects against breast cancer in vitro. Two human
      breast cancer cell lines (HTB26, MCF-7) were treated with catechin (Cox-1
      inhibitor) or NS398 (Cox-2 inhibitor) at 100 microM as both single and combined
      treatments. Reductions in cell growth were observed in both cell lines at 24 and
      72 h in both single and combined treatments (p<0.001). Combined treatment
      produced a significantly greater inhibition as compared to single agents alone.
      Upon cell cycle evaluation, Cox-1 and -2 antagonism increased G1 and G2 phase
      fractions in MCF-7 cells (p<0.001 and p<0.05 respectively). No additive changes
      were observed when the two agents were combined. An increase in the G2 phase was
      observed in the HTB26 cells when treated with NS398 alone (p<0.001). However, a
      decrease in the S-phase was observed when these cells were treated with NS398, as
      a single agent (p<0.01) or when the two agents were combined (p<0.01). The
      significant and additive effects exhibited by the combination of Cox-1 and -2
      inhibitors and their effects on cell cycle suggest that these agents could become
      an effective treatment modality for carcinoma of the breast.

PMID- 16964400
TI  - Extracellular acidosis elevates carbonic anhydrase IX in human glioblastoma cells
      via transcriptional modulation that does not depend on hypoxia.
AB  - Most solid tumors display extracellular acidosis, which only partially overlaps
      with hypoxia and induces distinct adaptive changes leading to aggressive
      phenotype. Although acidosis is mainly attributable to excessive production of
      lactic acid, it also involves carbonic anhydrase (CA) IX-mediated conversion of
      CO(2) to an extracellular proton and a bicarbonate ion transported to cytoplasm.
      CA IX is pre-dominantly expressed in tumors with poor prognosis and its
      transcription and activity are induced by hypoxia. Here we investigated whether
      low extracellular pH in absence of hypoxia can influence CA IX expression in cell
      lines derived from glioblastoma, a tumor type particularly linked with acidosis.
      Our data show that extracellular acidosis increased the level of CA IX protein,
      mRNA and the activity of minimal CA9 promoter that contains binding sites for HIF
      1 and SP-1 transcription factors. Mutation within each of these two biding sites
      reduced the promoter activity, but did not eliminate the increase by acidosis.
      Transfection of HIF-1alpha cDNA produced additive inducing effect with acidosis.
      Normoxic acidosis was accompanied by HIF-1alpha protein accumulation and
      transiently increased phosphorylation of ERK1/2. Expression of a dominant
      negative mutant of ERK2 reduced the CA9 promoter activity in both standard and
      acidic conditions. Similar result was obtained by inhibitors of MAPK and PI3K
      pathways, whose combination completely suppressed CA IX expression and abolished
      induction by acidosis. Altogether, our results suggest that acidosis increases
      the CA IX expression via a hypoxia-independent mechanism that operates through
      modulation of the basic CA9 transcriptional machinery.

PMID- 16964401
TI  - Gene silencing of human RAMP2 mediated by short-interfering RNA.
AB  - Adrenomedullin (AM) is a regulatory peptide widely expressed, along its
      receptors, in cells and tissues, of which it controls many basic and specific
      functions acting in an autocrine-paracrine manner. However, the unequivocal
      demonstration of the physiological relevance of the regulatory role of AM would
      require the study of cells where the endogenous AM system has been suppressed.
      For this task we developed a technique to silence the AM gene in human umbilical
      vein endothelial cells (HUVECs) and the human embryonal kidney cell line (HEK
      293). AM acts via two subtypes of receptor, named AM1 and AM2, which derive from
      the interaction of the calcitonin receptor-like receptors with two chaperones,
      called receptor activity modifying proteins (RAMP2 and RAMP3). Hence, we
      developed a protocol to suppress the human AM1 receptor by silencing the RAMP2
      gene by transfection with short interfering RNAs (siRNAs). HUVECs were
      transfected using a new Ambion transfection reagent. RAMP2 gene silencing was
      determined in HUVECs by measuring RAMP2 mRNA levels in transfected and control
      cells by real-time polymerase chain reaction. The RAMP2 gene silencing was
      approximately 60% and was observed 48 h after transfection. Matrigel assay in
      vitro was carried out to evaluate the effects of siRNA sequences. HUVECs cells
      were plated on matrigel and the analysis of capillary-like tubule formation
      showed that the cells were viable. The knockdown of the RAMP2 gene decreased the
      formation of tubes in response to 10(-8) M AM. The conclusion is drawn that siRNA
      technology can be successfully used in the investigations on AM and AM receptor
      functions.

PMID- 16964402
TI  - Highly liver-specific heme oxygenase-1 induction by interleukin-11 prevents
      carbon tetrachloride-induced hepatotoxicity.
AB  - Heme oxygenase (HO)-1, the rate-limiting enzyme in heme catabolism, can be
      induced in response to various oxidative stimuli, and its induction is thought to
      be critical in the cellular defense against oxidative tissue injuries. Carbon
      tetrachloride (CCl(4)) treatment of rats causes lipid peroxidation of cell
      membranes and produces massive hepatic injury. We previously demonstrated that HO
      1 induction following CCl(4) treatment is an essential part of the cellular
      defense against the CCl(4)-inducible toxic changes. As recombinant human
      interleukin-11 (rhIL-11) has been shown to induce HO-1 in cultured hepatoma
      cells, we examined the effect of rhIL-11 in vivo in rats on the CCl(4)-induced
      tissue injury. rhIL-11 treatment of animals by itself markedly induced HO-1 mRNA
      and its functional protein principally in the liver. rhIL-11 treatment (150
      microg/kg) of the CCl(4)-administered (1 ml/kg) animals led to a further increase
      in HO-1 mRNA, while it markedly suppressed CCl(4)-induced serum alanine
      transaminase, hepatic malondialdehyde formation, tumor necrosis factor-alpha
      mRNA, nitric oxide synthase mRNA, nuclear factor-kappaB DNA-binding activity, as
      well as inflammatory changes of hepatocytes. In contrast, inhibition of HO
      activity by tin-mesoporphyrin, a competitive specific inhibitor of HO, entirely
      abolished the cytoprotective effect of rhIL-11. These findings thus demonstrate
      that rhIL-11 confers significant protection against CCl(4)-induced hepatic injury
      by virtue of its liver-specific HO-1 induction.

PMID- 16964403
TI  - Promoter hypermethylation of the 14-3-3 sigma, SYK and CAGE-1 genes is related to
      the various phenotypes of urinary bladder carcinomas and associated with
      progression of transitional cell carcinomas.
AB  - To explore the significance of epigenetic mechanisms in urinary bladder
      carcinogenesis mediated by methylation of cytosine in CpG dinucleotides at 5'
      promoter regions, we analysed the methylation status of a broad panel of
      different genes in transitional cell carcinomas (TCC) and nonurothelial cancers,
      among which the 14-3-3 sigma, SYK and CAGE-1 genes were recognised as promising
      target genes. Using methylation-specific PCR, the rate of DNA hypermethylation
      proved to be related to the various histopathological cancer subtypes. The higher
      frequency of promoter methylation of the 14-3-3 sigma (57.1%) and SYK (64.3%)
      genes in high-grade, high-stage TCC in association with a reduced or even lacking
      immunohistochemical protein expression than in low-grade, low-stage TCC (28.6%
      and 42.9%, respectively), indicates that aberrant methylation of these genes
      plays an essential role in the progression of TCC. The importance of DNA
      hypermethylation in the conversion of TCC from a low to a high malignant
      potential was strongly supported by the finding that, unlike superficial low
      grade TCC, advanced muscle invasive TCC showed a concurrent promoter methylation
      of the 14-3-3 sigma, SYK and CAGE-1 genes. Squamous cell carcinomas revealed a
      peak incidence of hypermethylation of the 14-3-3 sigma gene (80%), and
      conversely, the lowest methylation frequency of the SYK gene (13.3%).
      Undifferentiated small cell carcinomas disclosed a promoter methylation of the 14
      3-3 sigma, SYK and CAGE-1 genes in only a quarter each for the cases. Although a
      correlation between the methylation status and gene activity in squamous cell and
      undifferentiated small cell carcinomas was not observed, the underexpression of
      the SYK protein products in both cancer types and additionally of the 14-3-3
      sigma protein in small cell carcinomas appeared to be related to the aggressive
      clinical behaviour of both these nonurothelial bladder carcinomas. The relevance
      of the high frequency of DNA hypermethylation of the CAGE-1 antigen in TCC and
      squamous cell carcinomas merits further study, particularly in relation to
      anticancer immunotherapy. The methylation status of the PTEN, COX-2, RUNX-3 and
      HIC-1 genes was found to be unaltered. In conclusion, the different patterns of
      aberrant methylation of the 14-3-3 sigma, SYK and CAGE-1 genes in the various
      histopathological cancer types of the urinary bladder point to a role in tumor
      cell differentiation, resulting in the phenotypical conversion of TCC into
      nonurothelial carcinomas and in the progression of TCC to a more malignant
      potential.

PMID- 16964404
TI  - CD40 expression in HCV-associated chronic liver diseases.
AB  - CD40 is expressed primarily on B cells and plays an important role in antigen
      presentation, B cell proliferation, and T cell activation. It has been reported
      that the CD40 signal modulates apoptosis and has an anti-viral effect in certain
      cells. Therefore, we investigated the expression and the function of CD40 in HCV
      associated chronic liver disease. The expression of CD40 on liver tissues was
      determined through immunohistochemistry on 50 liver specimens obtained from HCV
      positive patients. The effect of CD40 signaling on apoptosis of HepG2 cells was
      assessed using the MTT assay. The effect of CD40 stimulation on NF-kappaB
      activation was determined in NF-kappaB reporter gene-transfected HepG2 cells with
      the Luciferase assay. CD40 positive hepatocytes were observed in both periportal
      and lobular areas, accompanied by inflammation. In both areas, CD40 staining
      intensity became significantly stronger, correlating with the histological
      grading. Similarly, it became stronger with the progression of the histological
      staging in F1, F2 and F3 cases; however, the expression level decreased in F4
      cases. CD40 ligation induced apoptosis in HepG2 cells in the presence of 500
      ng/ml of actinomycin D, while CD40 ligation alone could not. Anti-CD40 monoclonal
      antibody caused NF-kappaB activation in HepG2 cells in a dose-dependent manner.
      These results suggest that hepatocyte over-expression of CD40 might play an
      important role in regulating hepatocyte survival and death in HCV-associated
      chronic liver diseases.

PMID- 16964405
TI  - Estradiol and resveratrol stimulating effect on osteocalcin, but not osteonectin
      and collagen-1alpha gene expression in primary culture of rat calvarial
      osteoblast-like cells.
AB  - Evidence is available that some endocrine disruptors, acting as selective
      estrogen receptor modulators (SERMs), interfere with osteoblast differentiation
      and function. Therefore, we investigated whether 17beta-estradiol, bisphenol-A
      (BSP), silymarin, genistein, resveratrol, procymidone, linurone and benzophenone
      3 (BP3) modulate differentiation of rat calvarial osteoblast-like (ROB) cells in
      primary in vitro culture. Disruptors were added at day 18 of culture and cells
      were harvested 48 h later. Real time-PCR revealed that estradiol and resveratrol
      enhanced osteocalcin mRNA expression in ROB cells, while other disruptors were
      ineffective. The expression of osteonectin and collagen-1alpha was not affected
      by any disruptor. Estradiol, resveratrol, genistein and BSP stimulated the
      proliferative activity of ROB cells. In contrast, procymidone and linurone
      inhibited the proliferative activity, and silymarin and BP3 were ineffective. The
      conclusion is drawn that i) only resveratrol is able, like estradiol, to
      stimulate the specialized functions of ROB cells, and ii) the proliferative
      activity of ROB cells is more sensitive to endocrine disruptors, some of which
      could probably act via a mechanism independent of their SERM activity.

PMID- 16964406
TI  - Role of vascular endothelial growth factor in protein loss of Menetrier's
      disease.
AB  - Vascular endothelial growth factor (VEGF) promotes protein leakage from blood
      vessels and endothelial cell growth. The expression of transforming growth factor
      (TGF)-alpha and its receptor is increased in the gastric mucosa of patients with
      Menetrier's disease. Since TGF-alpha stimulates the expression of VEGF mRNA in
      cultured keratinocytes, we hypothesized that VEGF may play an important role in
      the protein leakage of Menetrier's disease. Immunohistochemistry was performed
      using specific antibodies against VEGF and CD31 in gastric tissue specimens from
      7 patients with Menetrier's disease and 10 controls. The effect of recombinant
      TGF-alpha on VEGF production by cultured lamina propria mononuclear cells (LPMCs)
      was assessed. VEGF expression was detected for LPMCs and occasional epithelial
      cells of the gastric mucosa of Menetrier's patients. VEGF-positive LPMCs were
      increased in tissues from patients with Menetrier's disease (P<0.001). Of the
      LPMCs, T-lymphocytes and macrophages were the major sources of VEGF. CD31
      positive blood vessels were increased in Menetrier's tissue. (P<0.05).
      Recombinant TGF-alpha induced the production of VEGF in cultured LPMCs (P<0.05).
      In conclusion, the increased expression of VEGF, as a result of overproduction of
      TGF-alpha, may play a key role in the pathophysiology of Menetrier's disease.

PMID- 16964407
TI  - TGFbeta induces transdifferentiation of iBREC to alphaSMA-expressing cells.
AB  - Transforming growth factor beta (TGFbeta) both inhibits proliferation of
      macrovascular endothelial cells and promotes their transdifferentiation to alpha
      smooth-muscle-actin (alphaSMA)-expressing mesenchymal cells in vitro. Recently,
      we have confirmed that proliferation of immortalized bovine retinal microvascular
      endothelial cells (iBREC) is strongly inhibited by TGFbeta2. We now demonstrate a
      complete transition of both parental iBREC and single cell-derived subclones from
      cobblestone morphology to a ragged appearance as a consequence of incubation for
      a few days with 10 ng/ml TGFbeta1 or TGFbeta2. Depending on the type of culture
      medium, 5-40% of these cells strongly expressed alphaSMA after approximately 6
      days whereas expression of the endothelial cell-specific marker proteins von
      Willebrand factor and VE Cadherin (CD144) declined. Expression of alphaSMA,
      associated with formation of stress fibers, was first detected in single cells
      and then spread to adjacent cells, and declined slowly after prolonged
      cultivation in medium without TGFbeta2. However, re-constitution of vWF
      expression was not observed. TGFbeta2-induced phenotypic alterations were
      specific, as they were not caused by treatment of iBREC with VEGF, IGF-1 or bFGF.
      Induction of alphaSMA expression but not effects on morphology was strongly
      inhibited by bFGF, whereas IGF-1 enhanced TGFbeta2-induced alphaSMA expression.
      These findings may have an important impact on the understanding of development
      of microvascular complications of diabetes such as diabetic retinopathy.

PMID- 16964408
TI  - Inhibitory action of C22-fatty acids on DNA polymerases and DNA topoisomerases.
AB  - We reported previously that unsaturated linear-chain fatty acids of the cis
      configuration with a C18-hydrocarbon chain such as linoleic acid (cis-9, 12
      octadecadienoic acid, C18:2) could potently inhibit the activity of mammalian DNA
      polymerases (Biochim Biophys Acta 1308: 256-262, 1996). In this study, we
      investigated the inhibitory effects of cis-type C22-fatty acids including cis
      7,10,13,16,19-docosapentaenoic acid (DPA, C22:5) and cis-4,7,10,13,16,19
      docosahexaenoic acid (DHA, C22:6) on mammalian DNA polymerases and human DNA
      topoisomerases. Cis-13,16-docosadienoic acid (C22:2) was the strongest inhibitor
      of both DNA polymerases and topoisomerases of all C22-fatty acids tested. The
      inhibitory tendency by the fatty acids on DNA polymerases was the same as that of
      DNA topoisomerases, and the second strongest inhibitor was cis-13,16,19
      docosatrienoic acid (C22:3). The energy-minimized three-dimensional structures of
      the fatty acids were calculated and it was found that a length of 19-21 Angstrom
      and width of more than 7 Angstrom in C22-fatty acid structure were important for
      enzyme inhibition. The three-dimensional structure of the active site of both DNA
      polymerases and topoisomerases must have a pocket to join C22:2, and this pocket
      was 19.41 Angstrom long and 9.58 Angstrom wide.

PMID- 16964409
TI  - Mutational analysis of Kir6.1 in Japanese patients with coronary spastic angina.
AB  - The etiology of coronary spastic angina (CSA) remains uncertain. Mice lacking the
      gene encoding the inwardly rectifying K(+) channel Kir6.1 were developed as an
      animal model of CSA. We investigated whether mutation in the coding region of the
      Kir6.1 gene is detected in Japanese patients with CSA. The study population
      included 19 Japanese patients with CSA (10 men and 9 women with a mean age of
      61+/-14 years). Mutational analysis of the coding region of Kir6.1 was performed
      by direct sequencing. We found no missense or nonsense mutations in these
      samples, but we found in one female CSA patient, a single base substitution (C to
      T) at nucleotide position 111 in exon 2 of the coding region, which was
      heterozygous and did not cause amino acid substitution (Ile37Ile, silent
      mutation). In the remaining 18 patients, no base substitution was detected in the
      coding region of the Kir6.1 gene. No mutation that alters primary structure of
      Kir6.1 was detected in Japanese patients with CSA. The results indicate that
      abnormality in the primary structure of Kir6.1 may not be involved in the genetic
      pathogenesis of CSA in humans.

PMID- 16964410
TI  - crv4, a mouse model for human ataxia associated with kyphoscoliosis caused by an
      mRNA splicing mutation of the metabotropic glutamate receptor 1 (Grm1).
AB  - We describe a novel spontaneous autosomal recessive mutation, cervelet-4 (crv4),
      which arose in a BALB/c strain. Mice homozygous for the mutation exhibit
      principally a reduced body size, a congenital neurological phenotype
      characterized by ataxic gait and intention tremor, with no gross anomalies
      observed in brain or cerebellum, and skeletal anomalies. Using linkage analysis,
      we mapped the crv4 locus to the proximal region of chromosome 10, at the location
      of the Grm1 gene. Genetic complementation crosses between crv4 and Grm1 KO mice
      confirmed that crv4 is a new allele of Grm1. Molecular analysis of the Grm1 gene
      in mutant mice revealed the insertion of a 190-bp LTR fragment in intron 4. Our
      results also indicated that the presence of the LTR fragment caused the
      disruption of the Grm1 normal splicing process and complete absence of the wild
      type protein. crv4 is an interesting model to extend the study of Grm1 function
      and the pathological effects of Grm1 deficiency in vivo.

PMID- 16964411
TI  - The immediate upstream sequence of the mouse Ret gene controls tissue-specific
      expression in transgenic mice.
AB  - The RET gene is tightly regulated at the transcriptional level during embryo
      development, however in vitro experiments in cultured cells have failed to
      clarify the molecular mechanism of cell-type specificity of RET promoter
      activity. Therefore, we have generated transgenic mice in which the LacZ reporter
      gene is controlled by murine Ret promoter sequences to clarify in an in vivo
      model how this transcriptional regulation is achieved. We describe here the
      results of reporter gene expression in mice in which the transgene contained 380-
      and 1962-bp sequence upstream of the ATG start codon, derived from the mouse Ret
      promoter region, fused to the beta-galactosidase coding sequence. Transgenic mice
      showed well-defined patterns of beta-galactosidase staining obtained with both
      transgenes, suggesting that they were able per se to direct the reporter gene
      expression in specific districts, such as cranial ganglia, dorsal root ganglia,
      the heart and the kidney, partially recapitulating the profile of the endogenous
      Ret gene. In particular, proper expression in the developing excretory system
      seemed quite significant when considering that the appropriate regulation was
      obtained with a very short, 380 bp, fragment of Ret 5' flanking sequence.

PMID- 16964412
TI  - Using caffeoyl pyrrolidine derivative LY52, a potential inhibitor of matrix
      metalloproteinase-2, to suppress tumor invasion and metastasis.
AB  - LY52 is a caffeoyl pyrrolidine derivative designed to fit the S'1 active pocket
      of gelatinases that act in tumor invasion and metastasis. Herein, we examined the
      effects of LY52 on expression of matrix metalloproteinase (MMP)-2 expression in
      human breast cancer MDA-MB-231 cells and on in vitro invasion and in vivo
      metastasis. LY52 significantly blocked MMP-2 activity as evidenced by a decrease
      in the degradation of succinylated gelatin. Gelatin zymography analysis showed
      that LY52 (0.1-200 microg/ml) inhibited expression of active MMP-2 in
      concanavalin A-stimulated MDA-MB-231 cells. Inhibition of MMP-2 expression was
      also observed in tissue of tumor xenografts in mice that were orally administered
      LY52 (25 or 100 mg/kg). Furthermore, LY52 displayed an inhibitory effect on in
      vitro invasion of MDA-MB-231 cells and pulmonary metastasis of B16F10 murine
      melanoma cells in mice without significant toxic effects. These results suggest
      that LY52 is a potential MMP-2 inhibitor that may effectively suppress tumor
      invasion and metastasis.

PMID- 16964413
TI  - Leptin and leptin receptors in the prostate and seminal vesicles of the adult
      rat.
AB  - Leptin is an adipose tissue-secreted hormone that acts via specific receptors (Ob
      R), of which six isoforms are at present recognized (from Ob-Ra to Ob-Rf). Ob-Rb
      is the only isoform able to activate JAK-STAT and MAPK signaling cascades. A
      large body of evidence suggests that leptin and its receptors are involved in
      prostate physiology and pathophysiology in humans, but studies on the leptin
      system in the rat prostate are lacking. Reverse transcription-polymerase chain
      reaction showed the expression of mRNAs of leptin, Ob-Ra, Ob-Rb, Ob-Rc, Ob-Re and
      Ob-Rf in adult rat seminal vesicles and prostate (coagulating, dorsal, ventral
      and lateral lobes). Western blotting demonstrated the presence in these specimens
      of the Ob-Rb protein, and immunocytochemistry revealed that Ob-Rb was mainly
      located in their epithelial-cell component. Collectively, these findings strongly
      suggest that leptin and Ob-R may be involved in the autocrine-paracrine
      functional regulation of the epithelial cells of adult rat seminal vesicles and
      prostate.

PMID- 16964414
TI  - Coexistence of psoriasis and pemphigoid--only a coincidence?
AB  - It has previously been reported that pemphigoid coexists with psoriasis more
      frequently than it could be predicted on the basis of random distribution in the
      general population. In this study we present three psoriatic patients who
      developed tense blisters, which most likely were not provoked by anti-psoriatic
      treatment. Diagnosis of bullous pemphigoid in these cases was established by an
      overlay antigen mapping technique by laser confocal microscopy, immunoblotting
      and ELISA. In the context of these cases and the literature, we also discuss
      possible reasons for the coexistence of psoriasis and pemphigoid as well as
      selected aspects of diagnosis and therapy of patients simultaneously suffering
      from these two diseases.

PMID- 16964415
TI  - Methylation of green tea polyphenols affects their binding to and inhibitory
      poses of the proteasome beta5 subunit.
AB  - Previously, we showed that ester carbon-containing tea polyphenols, including (-)
      epigallocatechin gallate [(-)-EGCG] and (-)-epicatechin-3-gallate [(-)-ECG],
      potently inhibit proteasomal chymotrypsin-like activity. In addition, our in
      silico docking study suggested that a particular pose of (-)-EGCG could lead to
      potential covalent modification of the N-terminal threonine (Thr 1) of the
      proteasome beta5 subunit in the chymotrypsin-like active site. It has been
      suggested that some major biotransformation reactions, such as methylation, could
      result in reduced biological activity of (-)-EGCG in vivo. We hypothesize that
      methylation reduces binding of (-)-EGCG to the beta5 subunit of the proteasome
      and, therefore, decreases its proteasomal chymotrypsin-like-inhibitory potency.
      Here, we report that, while methylation has no effect on nucleophilic
      susceptibility of (-)-EGCG and (-)-ECG, it may disrupt the ability of these
      polyphenols to interact with Thr 1 of the proteasome beta5 subunit. In silico
      docking shows that methylation results in the tea polyphenols' ester carbon being
      moved away or blocked entirely from Thr 1. Additionally, methylation impairs the
      ability of (-)-EGCG and (-)-ECG to dock in a consistent low energy pose. These
      observations, no change in nucleophilic susceptibility, moving or blocking the
      ester carbon from Thr 1, and lack of a consistent docking pose, suggest that
      methylation disrupts the ability of (-)-EGCG and (-)-ECG to bind to the
      proteasome beta5 subunit, which may then diminish their proteasomal chymotrypsin
      inhibitory and, therefore, other biological activities.

PMID- 16964416
TI  - In utero transplantation of human hematopoietic stem/progenitor cells partially
      repairs injured liver in mice.
AB  - The aim of this study is to establish a novel mouse model with high achievement
      and chimerism by in utero transplantation of human hematopoietic stem/progenitor
      cells and to explore the possibility that human adult hematopoietic
      stem/progenitor cells can differentiate into hepatocyte-like cells and partially
      repair the liver damage induced by carbon tetrachloride (CCl(4)). Mononuclear
      cells (MNCs) were isolated from fresh human umbilical cord blood (hUCB) and
      CD34(+) cells were enriched from the MNCs by magnetic cell isolation. These cells
      were injected respectively into the fetal mice at 11-13 days of gestation. At one
      month after birth, the specific markers of human cells, human alpha-satellite
      sequence (h17alpha), CD14, CD34, CD45, and GPA were detected by PCR and FACS. At
      three and six months after birth, the established human-mouse chimeras were
      administered with CCl(4) by intraperitoneal injection. The biochemical markers
      (ALT, AST, ALP, albumin) in serum were determined and human hepatocyte-specific
      proteins, such as human albumin, hepatocyte nuclear factor-4, hepatocyte-specific
      antigen, tryptophan 2,3-dioxygenase and alpha fetoprotein were analyzed by PCR,
      RT-PCR, real-time PCR and immunohistochemistry staining, respectively. More than
      77% of recipients demonstrated human-mouse chimera. Significantly, hUCB
      hematopoietic stem/progenitor cells may differentiate into human hepatocyte-like
      cells with evidence of the expression of human hepatocyte-specific proteins as
      well as partially repair or protect liver damage induced by CCl(4). The mouse
      model described in this article provides a useful tool for the studies of
      regeneration of human hepatocyte-like cells from adult hematopoietic stem/
      progenitor cells as well as facilitates the therapeutic potential for liver
      diseases or damage by in utero transplantation.

PMID- 16964418
TI  - Identification of the mineralocorticoid receptor in human spermatozoa.
AB  - Aldosterone seems to play a role in the regulation of the electrolyte content of
      sperm and in the motility of spermatozoa. The aim of the study was to evaluate
      the presence of the mineralocorticoid receptor (MR) in human ejaculated
      spermatozoa. We have assayed MR on spermatozoa of freshly ejaculated sperm from
      healthy donors. The identification of MR was made by using immunohistochemistry
      and immunofluorescence analyses, while MR mRNA expression was evaluated by real
      time PCR assay. The immunohistochemical and immunofluorescence analyses showed
      positive staining both in the midpiece and in the tail of the spermatozoa.
      Relative quantification of MR by using real-time PCR shows that the mRNA
      expression of MR in spermatozoa is lower than in mononuclear leukocytes (positive
      controls). Sequencing showed complete identity between the sequence obtained from
      spermatozoa and the human MR cDNA sequence. Further studies should be performed
      in order to elucidate a possible physiological role of aldosterone in regulating
      electrolyte concentration, and the pro-oxidant effect of excess aldosterone in
      this new target tissue.

PMID- 16964417
TI  - Multiple colon carcinomas in a patient with Cowden syndrome.
AB  - Cowden syndrome is a non-adenomatous gastrointestinal polyposis syndrome with
      inactivation of PTEN, a dual-phosphatase tumor suppressor gene. Patients with
      loss of wildtype PTEN expression from one allele carry an increased risk of
      malignant breast, thyroid and brain tumors. However, the risk of malignant
      transformation in gastrointestinal polyps is still unclear. In this study, we
      describe a kindred with Cowden syndrome and identify a heterozygous germline
      mutation causing truncation of the PTEN tumor suppressor. The index patient was a
      56 year-old woman having multiple facial papules, acral keratosis, oral
      papillomatosis, multiple benign breast and thyroid tumors and gastrointestinal
      polyposis. Progression to invasive adenocarcinoma occured in two pre-existing
      hamartomatous polyps. Analysis of one of the carcinomas revealed somatic
      inactivation of the wildtype PTEN allele by exon-skipping. This case demonstrates
      that gastrointestinal hamartomas in Cowden syndrome patients can progress to
      invasive adenocarcinomas and should therefore be carefully monitored.

PMID- 16964419
TI  - Identification and characterization of the human StARD9 gene in the LGMD2A-region
      on chromosome 15q15 by in silico methods.
AB  - StAR (steroidogenic acute regulatory) proteins and proteins with StAR-related
      lipid transfer (START) domains are involved in lipid transport and metabolism,
      signal transduction, and transcriptional regulation. In this present study we
      characterized the StARD9 gene by bioinformatical methods. The human StARD9 gene
      (syn. KIAA1300), consisting of 11 exons, was located within human genome sequence
      CTD-2036P10 (AC090510). The complete coding sequence of human StARD9 cDNA was
      determined by DKFZp781J069 cDNA (CR749416), which was identified by using a
      partial coding sequence of human StARD9 cDNA (AB037721) as a query. The existing
      predicted gene model could be refined based on EST-analysis. Comparison of the
      human protein sequence with chimpanzee, rat, mouse and chicken homologs showed a
      98% (chimpanzee), 60% (rat), 60% (mouse) and 45% (chicken) amino-acid identity
      respectively. A lipid-binding START domain was identified within StARD9 protein.
      This is the first report on characterization of the StARD9 gene.

PMID- 16964420
TI  - Inhibition of oxidative stress-induced invasiveness of cancer cells by Ganoderma
      lucidum is mediated through the suppression of interleukin-8 secretion.
AB  - Epidemiological studies suggest that the intake of natural/nutrient products is
      inversely related to cancer risk. While oxidative stress, generating reactive
      oxygen species, has been linked to cancer initiation and progression, dietary
      antioxidants have reduced the risk of certain cancers. Experimental studies have
      demonstrated that antioxidants and phytochemicals could prevent cancer
      metastasis, and antioxidants were suggested as adjuvants in cancer therapy.
      Ganoderma lucidum is an Asian medicinal mushroom that has been used for the past
      two thousand years for the treatment of various diseases, including cancer. G.
      lucidum is currently popular as a dietary supplement in the form of tea, powder
      or extract. We have previously demonstrated that G. lucidum suppresses growth,
      angiogenesis and invasiveness of highly invasive and metastatic breast cancer
      cells. The present study was undertaken to evaluate the effect of G. lucidum on
      oxidative stress-induced metastatic behavior of poorly-invasive MCF-7 breast
      cancer cells. We show that G. lucidum inhibits oxidative stress-induced migration
      of MCF-7 cells by the down-regulation of MAPK signaling. G. lucidum suppressed
      oxidative stress stimulated phosphorylation of extracellular signal-regulated
      protein kinases (Erk1/2), which resulted in the down-regulation of expression of
      c-fos, and in the inhibition of transcription factors AP-1 and NF-kappaB. The
      biological effect of G. lucidum on cell migration was mediated by the suppression
      of secretion of interleukin-8 from MCF-7 cells exposed to oxidative stress. In
      summary, our results suggest that G. lucidum inhibits the oxidative stress
      induced invasive behavior of breast cancer cells by modulating Erk1/2 signaling
      and can be potentially considered as an antioxidant in adjuvant cancer therapy.

PMID- 16964421
TI  - Involvement of nuclear factor I-A1 in the regulation of regucalcin gene promoter
      activity in cloned normal rat kidney proximal tubular epithelial cells.
AB  - Nuclear factor I-A1 (NF1-A1) can bind to the TTGGC motif in the rat regucalcin
      gene promoter region. This study was undertaken to determine whether NF1-A1 is
      involved in the enhancement of the rat regucalcin gene promoter activity using
      the -710/+18 LUC construct (wild-type) or -710/+18 LUC construct with the
      deletion of -523/-435 including the TTGGC motif (mutant) in cloned normal rat
      kidney proximal tubular epithelial NRK52E cells. Cells were transfected with the 
      710/+18 LUC construct vector or the -710/+18 LUC construct with the deletion of 
      523/-435. NRK52E cells (wild-type) or NRK52E cells transiently transfected with
      HA-NF1-A1/phCMV2 were cultured for 48 h in a medium containing either vehicle or
      BS (5%) in the presence or absence of various factors. HA-NF1-A1 was localized in
      the nucleus of wild-type cells. Luciferase activity was significantly increased
      as compared to that of wild-type cells. This increase was significantly enhanced
      in the presence of phorbol 12-myristate 13-acetate (PMA; 10(-6) M). Such an
      enhancement was not seen by culture with Bay K 8644 (10(-6) M) or dibutyryl
      cyclic AMP (10(-4) M). The increase in luciferase activity in NRK52E cells
      transfected with HA-NF1-A1 was not observed in the presence of dibucaine (10(-6)
      M), staurosporine (10(-9) M), or PD 98059 (10(-8) M), which is an inhibitor of
      various protein kinases. Such an inhibition was also seen in the presence of
      vanadate (10(-6) M) or okadaic acid (10(-6) M), an inhibitor of protein
      phosphatase. The increase in luciferase activity in NRK52E cells transfected with
      HA-NF1-A1/ phCMV2 was not seen in the mutant with deletion of -523/-435. The
      increase in luciferase activity in HA-NF1-A1/ phCMV2-transfected NRK52E cells was
      not significantly enhanced in the cells transiently co-transfected with HA-RGPR
      p117/phCMV2, which could increase the regucalcin gene promoter activity using the
      -710/+18 LUC construct (wild-type). This study demonstrates that NF1-A1 enhances
      the regucalcin promoter activity which is related to the TTGGC motif, and that
      its enhancing effect is partly mediated through phosphorylation in NRK52E cells.

PMID- 16964422
TI  - Morphological identification of hepatitis C virus E1 and E2 envelope
      glycoproteins on the virion surface using immunogold electron microscopy.
AB  - It is known that hepatitis C virus (HCV) particles are spherical, 55-65 nm
      particles with fine surface projections of about 6 nm in length and with a 30-35
      nm inner core. We have reported that free HCV particles labeled with gold
      particles specific to the HCV E1 glycoprotein are located in 1.14-1.16 g/ml
      fractions from plasma samples with high HCV RNA titers after sucrose density
      gradient centrifugation. However, the morphology of the HCV E2 glycoprotein on
      the virion has not yet been elucidated. To visualize HCV E2 localization on the
      virion, we used the same plasma samples where HCV particles were clearly shown.
      An indirect immunogold electron microscopic study was carried out using
      monoclonal and polyclonal anti-HCV E2 antibodies. HCV-like particles specifically
      reacted with the anti-HCV E2 antibodies. Moreover, to evaluate the localization
      of the HCV E1 and E2 glycoproteins on the virion surface, an immunogold electron
      microscopic study using double labeling with anti-HCV E1 antibodies and anti-HCV
      E2 antibodies was also performed. These particles also specifically reacted with
      both anti-E1 and E2 antibodies. This is the first report showing the presence of
      both HCV E1 and E2 glycoproteins on HCV virion surface in human plasma samples.

PMID- 16964423
TI  - Effects of lysine to arginine mutations in HIV-1 Vif on its expression and viral
      infectivity.
AB  - We previously demonstrated that the expression in cells of human immunodeficiency
      virus type 1 (HIV-1) Vif is maintained at low level by proteasome-degradation. We
      examined the contribution of 16 lysines present in Vif (NL432 clone), which is
      composed of 192 amino acids (aa), to its expression within cells and to viral
      infectivity for non-permissive cells. To this end, various lysine-arginine
      mutations were introduced into wild-type (wt) Vif, and the mutational effects
      were monitored by transfection experiments. When all the lysines were changed to
      arginines, the mutant Vif was expressed in cells at much higher level than wt and
      was much more stable. Both N-terminal (aa nos. 34 and 36) and C-terminal (aa nos.
      179 and 181) lysines were found to be almost sufficient for wt property.
      Different from this observation, one of the lysines at aa nos. 22 and 26 was
      demonstrated to be essential for the virus to grow in non-permissive cells. Our
      results showed that there is no clear co-relationship between the expression
      level of HIV-1 Vif and viral infectivity.

PMID- 16964424
TI  - Microarray profiling of gene expression patterns in glomerular cells of
      astaxanthin-treated diabetic mice: a nutrigenomic approach.
AB  - We have demonstrated that astaxanthin reduces glomerular oxidative stress as well
      as inhibits the increase in urinary albumin in diabetic db/db mice. The aim of
      the present study was to determine the gene expression patterns in the glomerular
      cells of the diabetic mouse kidney, and to investigate the effects of astaxanthin
      on the expression of these genes using a high-density DNA microarray. The diet
      administered to the astaxanthin-supplementation group was prepared by mixing a
      control powder with astaxanthin at a concentration of 0.02%. Glomerular cells
      were obtained from the kidneys of mice by laser capture microdissection.
      Preparation of cRNA and target hybridization were performed according to the
      Affymetrix GeneChip eukaryotic small sample target labeling assay protocol. The
      gene expression profile was evaluated by the mouse expression set 430A GeneChip.
      Array data analysis was carried out using Affymetrix GeneChip operating and
      Ingenuity Pathway analysis software. Comparison between diabetic db/db and non
      diabetic db/m mice revealed that 779 probes (3.1%) were significantly affected,
      i.e. 550 probes were up-regulated, and 229 probes were down-regulated, both at
      levels of >/=1.5-fold in the diabetic mice. Ingenuity signal analysis of 550 up
      regulated probes revealed the mitochondrial oxidative phosphorylation pathway as
      the most significantly affected caronical pathway. The affected genes were
      associated with complexes I, III, and IV located on the mitochondrial inner
      membrane, and the expression levels of these genes were decreased in mice treated
      with astaxanthin as compared to the levels in the control mice. In addition, the
      expression of many genes associated with oxidative stress, collagen synthesis,
      and transforming growth factor-beta signaling was enhanced in the diabetic mice,
      and this enhancement was slightly inhibited in the astaxanthin-treated mice. In
      conclusion, this genome-wide nutrigenomics approach provided insight into genes
      and putative genetic pathways that are thought to be affected by stimulation by
      high-glucose concentrations. In addition, the present approach may help us gain a
      better understanding of the genes and pathways involved in the anti-diabetic
      mechanism of astaxanthin.

PMID- 16964425
TI  - Protection of aortic endothelial function in both normal and diabetic rats by
      intravenous bolus injection of a medium-chain triglyceride: fish oil emulsion.
AB  - The bolus intravenous injection of a novel medium-chain triglyceride:fish oil
      emulsion (MCT:FO) was recently proposed as a tool to provoke a rapid and
      sustained increase of cell phospholipid content in long-chain polyunsaturated
      omega3 fatty acids, for instance in selected subjects prior to anesthesia and
      surgery. In this study, therefore, the possible protective effect of MCT:FO upon
      aortic endothelial function was investigated in both normal and diabetic rats.
      The animals were injected intravenously 20 h before sacrifice with 1.0 ml of
      either saline, MCT:FO or a control medium-chain triglyceride:long-chain
      triglyceride emulsion. The vasomotor response of isolated aortic rings was then
      explored by assessing the relaxation provoked by increasing concentrations of
      acetylcholine in rings contracted with phenylephrine. Such measurements were
      performed before and after exposure of the aortic rings to suitable
      concentrations of oxidized LDL. In both normal and diabetic rats, the prior
      injection of the MCT:FO emulsion protected the aortic rings against the
      deleterious effect of oxidized LDL. In the diabetic rats, a beneficial effect of
      the MCT:FO emulsion was even observed prior to exposure of the aortic rings to
      oxidized LDL. These findings support the view that this novel procedure is indeed
      appropriate to protect endothelial function against oxidative stress.

PMID- 16964426
TI  - Comparison of human chorionic gonadotropin +beta and invasive trophoblast antigen
      disappearance rates in serum after evacuation of molar pregnancy.
AB  - After the evacuation of a hydatidiform mole, the spontaneous regression or the
      persistent trophoblastic disease (PTD) needing chemotherapy, is monitored by
      determining the serum human chorionic gonadotropin (hCG) concentration.
      Hyperglycosylated hCG (invasive trophoblast antigen, ITA) has been suggested to
      be of clinical value in the diagnosis and follow-up of gestational trophoblastic
      disease including PTD. To further document the relationship between ITA and hCG
      in spontaneous post-molar regression and during chemotherapy treatment of PTD, we
      used distinct immunoassays to measure the concentrations of hCG+beta and ITA in
      serum from three groups of patients after the evacuation of moles. For each group
      [uneventful post molar hCG regression, group 1; PTD treated with Methotrexate
      (MTX) (mono-chemotherapy), group 2; and PTD with MTX and poly-chemotherapy (EMA
      CO), group 3], we compared the time course of the serum concentrations after
      evacuation, and determined the disappearance rates (half-lives) within and
      between treatment groups. Significantly longer mean serum half-lives for hCG+beta
      and ITA were found in the poly-chemotherapy (group 3: 3.02 and 2.51 weeks) as
      compared to the mono-chemotherapy group (group 2: 0.96 and 0.90 weeks) and the
      uneventful regression group (0.81 and 0.66 weeks) (each, p=0.003), but no
      differences were observed between the mono-chemotherapy and the uneventful
      regression group. Significantly shorter mean half-lives for ITA than those
      calculated for hCG+beta were observed in all three groups of patients. The
      implication and the possible clinical value of the more rapid regression of ITA
      to baseline levels as compared to hCG+beta remain to be investigated
      prospectively.

PMID- 16964427
TI  - UVB radiation induces expression of HIF-1alpha and VEGF through the
      EGFR/PI3K/DEC1 pathway.
AB  - EGFR is involved in the UV signal transduction pathway leading to skin cancer. UV
      radiation, mediated by EGFR, induces activation of PI3 kinase and AKT with a
      result of activation of a number of transcription factors. Transcription factor
      HIF-1alpha correlates with tumorigenicity and angiogenesis. Transcription factors
      DEC1 and DEC2 also play pivotal roles in multiple signaling pathways impacting
      various biological processes including development, cell differentiation, cell
      death, and oncogenesis. We investigated whether UV radiation and associated
      hypoxia induce expression of HIF-1alpha and its target genes such as VEGF and the
      signaling pathway mediating such responses. We found that UV radiation induced
      HIF-1alpha and VEGF protein expression in a dose- and time-dependent manner in
      cultured human keratinocytes. UV radiation also induced VEGF mRNA expression in a
      dose-dependent manner with maximum effect at 4 h post treatment, but did not
      affect HIF-1alpha mRNA expression. We also observed that UV radiation induced
      activation of EGFR in a time- and dose-dependent manner which was inhibited by
      EGFR inhibitor PD153035. In egfr (-/-) MEF cells, UV radiation did not induce HIF
      1alpha and VEGF expression, in contrast, in egfr (+/+) MEF cells, UV radiation
      strongly induced HIF-1alpha and VEGF expression. EGFR kinase inhibitor, PD153035,
      inhibited UV-induced HIF-1alpha and VEGF protein expression in a dose-dependent
      manner. Further, we found that PI3K inhibitors, LY294002 and Wortmannin,
      inhibited HIF-1alpha and VEGF expression induced by UV radiation. In DEC1 (-/-)
      HaCat cells, UV radiation did not induce HIF-1alpha and VEGF expression, in
      contrast, in DEC1 (+/+) HaCat cells, UV radiation strongly enhanced HIF-1alpha
      and VEGF protein expression. We conclude that UV radiation induces HIF-1alpha and
      VEGF expression via the EGFR/PI3K/DEC1 signaling pathway.

PMID- 16964428
TI  - Mucosal function in rat jejunum and ileum is altered by induction of colitis.
AB  - Many studies dealing with trinitrobenzene sulfonic acid (TNBS) colitis in rats
      have been carried out referring only to the colon. In humans, ulcerative colitis
      (UC) can extend a variable distance into the terminal ileum in a phenomenon known
      as backwash ileitis (BWI). The aim of this study was therefore to examine the
      effect of TNBS-induced colitis on different aspects of the rat ileum and jejunum.
      We hypothesized that TNBS administration would lead to a systemic influence on
      the small intestine. Rats were induced colitis by administration of 0.25 ml of
      2,4,6-trinitrobenzene sulfonic acid and 72 h after colitis induction animals were
      sacrificed. Segments were taken of the colon, ileum and jejunum. In addition to
      mucin mRNA expression, morphological changes were observed in the jejunum and
      ileum. We examined the mRNA expression and biochemical activity of brush border
      enzyme, sucrase iso-maltase and aminopeptidase, in all three segments. The
      villous surface area of colitis-induced rats was smaller in jejunum and ileum
      compared to control. In the jejunum of TNBS-induced rats, goblet-cell volume
      increased and their density decreased. The relative amount of MUC2 mRNA decreased
      in the jejunum, ileum and colon of colitis rat. However, MUC3 mRNA expression
      increased in the ileum and colon of these rats. Sucrase isomaltase expression and
      activity decreased in the ileum of TNBS-induced rats, while aminopeptidase
      activity was lower in the jejunum. These observations suggest that intrarectal
      administration of TNBS to rats influences not only their colon and terminal
      ileum, but also the proximal ileum and jejunum. Involvement of the ileum and
      jejunum in TNBS-induced colitis may be related to the systemic reaction of the
      immune system and mucosa to colitis.

PMID- 16964429
TI  - Sequence analysis shows that Lifeguard belongs to a new evolutionarily conserved
      cytoprotective family.
AB  - Cellular sensitivity to apoptotic stimuli is determined by several regulatory
      proteins. The biological and biomedical impact of these regulatory proteins is of
      fundamental importance for understanding and controlling apoptotic processes. We
      used a bioinformatic approach to characterise the antiapoptotic protein Lifeguard
      (LFG). LFG is an evolutionarily well-conserved protein with homologues in many
      species. Due to its hydrophobic nature it is predicted to reside in cellular
      membranes, namely the endoplasmatic reticulum and the plasma membrane, with seven
      transmembrane spanners and a small cytoplasmic domain. The consensus motif of a
      protein family with unknown function UPF0005 was found in the C-terminus. The
      structure of Lifeguard resembles the antiapoptotic protein Bax Inhibitor-1 (BI
      1). Concordantly, it was shown that Bax co-immunoprecipitates with LFG. Our
      results indicate that LFG belongs to a new cytoprotective family with
      evolutionarily conserved functions in the prevention of programmed cell death.

PMID- 16964430
TI  - Role of bone morphogenetic protein 2 in the crosstalk between endothelial
      progenitor cells and mesenchymal stem cells.
AB  - In recent studies, we and others have demonstrated that bone morphogenetic
      protein-2 (BMP-2) promotes vascularization, inhibits hypoxic cell death of cancer
      cells and may be involved in tumor angiogenesis. The activation of circulating
      endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) represents
      a crucial factor in the process of postnatal neovascularization. BMP-2 protein
      expression has been detected in several tumor tissues and BMP receptors are
      expressed in EPCs and MSCs. We therefore analysed the influence of recombinant
      human (rh) BMP-2 on the function of human EPCs and human bone marrow derived
      MSCs. Treatment of EPCs isolated from peripheral blood with rhBMP-2 did not
      induce any significant changes in EPC viability but induced a dose-dependent
      activation of chemotaxis. Incubation of human MSCs isolated from bone marrow
      aspirates with rhBMP-2 revealed no significant effect on MSC proliferation.
      Incubation of EPCs with supernatants of MSCs significantly increased the cell
      viability compared to controls cultivated with endothelial cell medium. Protein
      and mRNA expression of the vascular endothelial growth factor (VEGF) family
      member, placental growth factor (PlGF), which is known to be involved in the
      expansion and recruitment of EPCs, was induced in MSCs after treatment with rhBMP
      2. We conclude that tumor- associated BMP-2 secretion might promote tumor
      angiogenesis by chemotactic effects on EPCs circulating in the peripheral blood
      and by increased secretion of paracrine angiogenic growth factors including PlGF
      in MSCs of the tumor stroma.

PMID- 16964431
TI  - Acute in vivo administration of a fish oil-containing emulsion improves post
      ischemic cardiac function in n-3-depleted rats.
AB  - A novel i.v. lipid preparation (MCT:FO) containing 80% medium chain
      triacylglycerols and 20% fish oil was recently developed to rapidly replenish
      cell membrane phospholipids with omega 3 (n-3) polyunsaturated fatty acids
      (PUFA). In regard of this property, we investigated the effect of a single i.v.
      administration of MCT:FO on the recovery of cardiac function after ischemia in
      control and n-3-depleted rats. Results were compared with those obtained either
      with a control preparation, where FO was replaced by triolein (MCT:OO), or with
      saline. Saline (1 ml) or lipid preparation (also 1 ml) was injected as a bolus
      via the left saphenous vein. After 60 min the heart was removed and perfused for
      20 min in normoxic conditions according to Langendorff. Thereafter, the heart was
      subjected to a 20 min zero-flow normothermic ischemia, followed by 40 min
      reperfusion. Cardiac mechanical and metabolic functions were monitored. In
      control rats, the previous administration of a lipid preparation (MCT:FO or
      MCT:OO) versus saline improved cardiac function during aerobic reperfusion post
      ischemia. N-3-depleted rats showed decreased basal cardiac function and impaired
      recovery following ischemia. However, the bolus injection of MCT:FO opposed the
      deleterious effect of long-term n-3-deficiency and, in this respect, was superior
      to MCT:OO over the first 20 min of reperfusion. This novel approach to rapidly
      correct n-3 PUFA-deficiency might be clinically relevant and offer interesting
      perspectives in the management of acute ischemic accidents.

PMID- 16964433
TI  - Preclinical investigations of a medium-chain triglyceride:fish oil emulsion. I.
      Effects of bovine milk lipoprotein lipase on lipid composition.
AB  - The bolus intravenous injection of a novel medium-chain triglyceride:fish oil
      emulsion (MCT:FO, 8:2, w:w) was recently found to increase within 60 min the
      leucocyte and platelet phospholipid content of long-chain polyunsaturated omega3
      fatty acids. The present report deals with the effects of bovine milk lipoprotein
      lipase on the lipid composition of this emulsion. The results are compared to
      those obtained with either a pure fish oil emulsion or a medium-chain
      triglyceride: long-chain triglyceride:fish oil emulsion (MLF, 5:4:1). Emphasis is
      placed on i) differences in the fate of distinct fatty acids initially present in
      the triglycerides, di glycerides and phospholipids, ii) the generation of
      unesterified fatty acids relative to their initial content in each emulsion, and
      iii) the time course for these various events. The comparison between the three
      emulsions under consideration also provides information relevant to their
      respective sensitivity to lipoprotein lipase and suitability in terms of the
      generation of distinct unesterified fatty acids, including long-chain
      polyunsaturated omega3 fatty acids. Furthermore, attention is drawn to the
      greater efficiency for the hydrolysis of fatty acids from diglycerides as
      compared to triglycerides and a transient increase in the paired C8:0/C10:0 ratio
      in the diglycerides generated from the MCT:FO or MLF emulsion. The present study
      thus affords novel information relevant to the possible use of the MCT:FO
      emulsion in human subjects.

PMID- 16964432
TI  - A conditionally replicative adenovirus that codes for a TK-GFP fusion protein
      (Ad5Delta24TK-GFP) for evaluation of the potency of oncolytic virotherapy
      combined with molecular chemotherapy.
AB  - The utility of conditionally replicative adenoviruses (CRAds) in cancer gene
      therapy is based on their ability to destroy tumor cells by oncolysis. However,
      in order to achieve adequate therapeutic response, CRAds have to spread through
      the tumor tissue by replication. Thus, to study the potency of these viruses to
      replicate and penetrate in tumors, we created a herpes simplex virus type 1
      thymidine kinase-green fluorescent protein fusion gene (TK-GFP) encompassing CRAd
      (Ad5Delta24TK-GFP), whose tumor selectivity is mediated by a retinoblastoma (Rb)
      binding site mutation. In addition, we evaluated the oncolytic efficacy of
      Ad5Delta24TK-GFP in combination with the TK/ganciclovir (GCV) system. Based on
      our results, Ad5Delta24TK-GFP replicates in cancer cells resulting in oncolysis
      and can efficiently penetrate into tumors. Additionally, the combination of GCV
      with Ad5Delta24TK-GFP augmented cell death in vitro but this was not observed in
      vivo: tumor growth was significantly reduced by oncolysis when compared to non
      replicative virus (p<0.001), but administration of GCV did not significantly
      enhance oncolysis. This suggests that in certain conditions, TK/GCV-mediated cell
      killing may be counterproductive to replication and oncolysis, which on the other
      hand might be useful feature for clinical trials in case of replication
      associated toxicity.

PMID- 16964434
TI  - Proteomic analysis of rat cerebral cortex, hippocampus and striatum after
      exposure to morphine.
AB  - Although a series of proteins in the brain have been shown to be qualitatively or
      quantitatively dysregulated following morphine administration, a systematic
      proteomic study has not been carried out so far. We therefore aimed to show the
      effect of morphine on protein levels in the rat brain. For this purpose rats were
      given a morphine base in subcutaneously placed pellets and subsequently the
      cerebral cortex, hippocampus and striatum were taken for proteomic studies after
      three days. Extracted proteins were run on two-dimensional gel electrophoresis,
      scanned and quantified by specific software. Proteins with significantly
      different levels were analysed by mass spectrometry (MALDI-TOF-TOF). Twenty-six
      proteins were found to be differentially expressed and were unambiguously
      identified. Dysregulated proteins were from several protein pathways and cascades
      including signaling, metabolic, protein handling, antioxidant and miscellaneous
      classes. These findings represent an initial approach to the generation of a
      'morphinome' and may form the basis for further protein chemical studies as a
      valuable analytical tool. Moreover, the study reveals morphine-regulated proteins
      in different brain areas and indicates the pathways involved following morphine
      administration in the rat, the main species for pharmacological studies in the
      field.

PMID- 16964435
TI  - The effect of stromal cell-derived factor 1 (SDF1/CXCL12) genetic polymorphism on
      HIV-1 disease progression.
AB  - The human immunodeficiency virus type 1 (HIV-1) epidemic is increasing in Brazil,
      and little information has been reported about the genetic host factors related
      to HIV-1 infection in the Brazilian population. A polymorphism in the conserved
      3' untranslated region of the stromal cell-derived factor 1 (SDF1/CXCL12) gene
      has been related either to resistance to HIV-1 infection and delayed progression
      to AIDS or to rapid disease progression and death. A longitudinal study was
      conducted to evaluate the association of the SDF1 polymorphism and the
      progression of HIV-1 infection in 161 asymptomatic patients infected with HIV-1
      (ASYMPT) and 617 patients with AIDS (SYMPT) from Londrina and the surrounding
      region, southern Brazil. The endpoints used were the development of AIDS, death,
      and the slopes of the CD4+ T cell counts and HIV-1 RNA plasma levels. Among the
      161 ASYMPT patients, all of the 7 patients (4.3%) homozygous for the mutation
      remained asymptomatic (p=0.1906); 6 of them had not initiated antiretroviral
      therapy. Among the 617 patients with AIDS, 40 (6.5%) progressed to death. Of
      these, 33/388 (8.5%) did not have the SDF1-3'A allele, 6/196 (3.1%) were
      heterozygous and 1/33 (3.0%) was homozygous for the SDF1-3'A allele (p=0.029).
      The SDF1 genotypes were not associated with the surrogate markers of HIV-1
      disease progression such as the CD4+ T cell decline and plasma HIV-1 RNA levels.
      The results observed in this study support the hypothesis that the mutation of
      SDF1-3'A could have a possible late-stage protective effect on HIV-1 disease
      progression in the Brazilian population.

PMID- 16964438
TI  - Ameliorating role of caffeic acid phenethyl ester (CAPE) against isoniazid
      induced oxidative damage in red blood cells.
AB  - Isoniazid (INH) still remains a first-line drug both for treatment and
      prophylaxis of tuberculosis, but various organs toxicity frequently develops in
      patients receiving this drug. We aimed to investigate possible toxic effects of
      INH on rat red blood cells (RBCs), and to elucidate whether Caffeic acid
      phenethyl ester (CAPE) prevents a possible toxic effect of INH. Experimental
      groups were designed as follows: control group, INH group, INH + CAPE group.
      Compared with the control, the INH caused a significant increase in superoxide
      dismutase (SOD) activity and malondialdehyde (MDA) levels, and a decrease in
      glutathione peroxidase (GSH-Px) and catalase (CAT), which are recently used to
      monitor the development and extent of damage due to oxidative stresses. CAPE
      administration to INH group ameliorated above changes due to INH.

PMID- 16964437
TI  - Differential subcellular localization and activity of kelch repeat proteins
      KLHDC1 and KLHDC2.
AB  - We have previously identified and characterized human KLHDC2/HCLP-1, a kelch
      repeat protein that interacts with and inhibits transcription factor LZIP. In
      this study, we identified and characterized a paralog of KLHDC2 called KLHDC1.
      KLHDC1 and KLHDC2 share about 50% identity at the level of amino acid sequence
      and both gene loci localize to human chromosome 14q21.3. This cluster of KLHDC1
      and KLHDC2 genes is highly conserved in vertebrates ranging from pufferfish to
      human. Both genes are expressed highly in skeletal muscle, but weakly in various
      other tissues. While KLHDC2 was predominantly found in the nucleus, KLHDC1 is a
      cytoplasmic protein. Neither KLHDC1 nor KLHDC2 binds to actin. In addition,
      KLHDC1 was unable to inhibit LZIP/CREB3-mediated transcriptional activation.
      Thus, KLHDC1 and KLHDC2 have differential localization and activity in cultured
      mammalian cells.

PMID- 16964439
TI  - Carcinogenesis related to intense pulsed light and UV exposure: an experimental
      animal study.
AB  - This study examines whether intense pulsed light (IPL) treatment has a
      carcinogenic potential itself or may influence ultraviolet (UV)-induced
      carcinogenesis. Secondly, it evaluates whether UV exposure may influence IPL
      induced side effects. Hairless, lightly pigmented mice (n=144) received three IPL
      treatments at 2-week intervals. Simulated solar radiation was administered
      preoperatively [six standard erythema doses (SED) four times weekly for 11 weeks]
      as well as pre- and postoperatively (six SED four times weekly up to 26 weeks).
      Skin tumors were assessed weekly during a 12-month observation period. Side
      effects were evaluated clinically. No tumors appeared in untreated control mice
      or in just IPL-treated mice. Skin tumors developed in UV-exposed mice
      independently of IPL treatments. The time it took for 50% of the mice to first
      develop skin tumor ranged from 47 to 49 weeks in preoperative UV-exposed mice
      (p=0.94) and from 22 to 23 weeks in pre- and postoperative UV-exposed mice
      (p=0.11). IPL rejuvenation of lightly pigmented skin did not induce pigmentary
      changes (p=1.00). IPL rejuvenation of UV-pigmented skin resulted in an immediate
      increased skin pigmentation and a subsequent short-term reduced skin pigmentation
      (p<0.002). Postoperative UV radiation resulted in re-pigmentation of IPL-induced
      pigment reduction (p=0.12). No texture changes were observed. Postoperative edema
      and erythema were increased by preoperative UV exposure (p<0.002). IPL
      rejuvenation has no carcinogenic potential itself and does not influence UV
      induced carcinogenesis. UV exposure influences the occurrence of side effects
      after IPL rejuvenation in an animal model.

PMID- 16964440
TI  - Description and genetic mapping of Polypodia: an X-linked dominant mouse mutant
      with ectopic caudal limbs and other malformations.
AB  - In this report we present a spontaneous mouse mutant, named Polypodia (Ppd), that
      primarily exhibits ectopic, ventral/caudal limbs and associated pelvic girdle
      malformation or duplication. Less penetrant features include diphallia,
      microphthalmia, small kidney, curled or kinked tail, forelimb anomaly, and skin
      papillae. Ppd mice have a normal karyotype and no large-scale genomic deletions
      or insertions by BAC-based array comparative genomic hybridization (CGH). Ppd is
      X-linked dominant with approximately 20% penetrance on the C3H background and
      maps to X:61.6 Mb-X:71.24 Mb. The limb and a subset of the nonlimb anomalies are
      similar to those in offspring from retinoic acid-treated dams at E4.5-5.5 and
      feature overlap with the Disorganization mouse mutant and human patients with
      ectopic legs. We hypothesize that Ppd affects very early steps in the formation
      of caudal structures including limb and appendage number. The existence of
      noncaudal anomalies implies the involvement of Ppd in a broad array of cell fate
      decisions.

PMID- 16964441
TI  - The expression profile of the H19 gene in cattle.
AB  - The expression of the H19 gene has been well studied in fetal human and mouse
      tissues but not in cattle. It is generally believed that H19 is abundantly
      expressed in the early stages of embryogenesis and is repressed postnatally. We
      report the expression pattern of this gene in cattle in a total of 120 fetal
      organ combinations and in a total of 108 adult-organ combinations using
      quantitative real time PCR. In fetal tissues, H19 was abundantly expressed in
      amnion, chorion, and allantois. Fetal liver, lung, heart, spleen, eye, rib,
      mammary gland, and cotyledon showed moderate expression, while intestine and
      brain showed lower expression levels. For some organs examined in this study, the
      expression pattern in cattle fetal organs was similar to that of human, mouse,
      and sheep. For adult organs, H19 was highly expressed in muscle and moderately
      expressed in liver, lung, heart, kidney, pancreas, and ovary. Low expression
      levels were observed for adult spleen, caruncle, and endometrium. Of considerable
      interest was the observation that H19 transcripts have not been detected in the
      mouse and human kidney or in the mouse spleen. In contrast, we observed
      significant expression levels in adult kidney and low expression levels in adult
      spleen. In a comparison of adults and fetuses, significant differences in H19
      expression levels were found for liver, lung, heart, and spleen. The expression
      pattern in adults implies that, in addition to possible roles in embryogenesis,
      the H19 gene may have other functions.

PMID- 16964442
TI  - Identification of candidate maternal-effect genes through comparison of multiple
      microarray data sets.
AB  - Transcriptional profiling by microarray hybridization has become a standard
      method to analyze global gene expression and has resulted in the availability of
      enormous amounts of experimental data. Given the number of different microarray
      platforms currently in use, it is critical to determine how reproducible results
      are from one platform to another. Additional variability may also arise from
      tissue collection and protocol differences among laboratories. In an effort to
      identify genes whose maternal mRNA pools are critical during preimplantation
      development, we compared published results of three independent studies of the
      mouse preimplantation embryo transcriptome, each performed in a different
      laboratory using different microarray platforms. We searched the combined data
      set for genes whose expression patterns were consistent among the three
      experiments. Querying for presence or absence at single developmental windows
      indicates that between 52% and 60% of genes are in agreement among the three
      experiments. Searching for expression patterns across three developmental windows
      (oocyte + 1-cell, 2- through 8-cell, and blastocyst stage) revealed approximately
      33% agreement among the three experiments, although the majority of these genes
      were either always present or always absent. Using this approach, we identified
      51 genes with a predicted expression pattern of maternal RNA only (not present
      during 2-cell through 8-cell or at the blastocyst stage). RT-PCR validation
      indicates 37 (72%) of these candidates have the microarray-predicted expression
      pattern and represent candidate maternal-effect genes. Based on our analysis, we
      conclude that data mining microarray experiments in this way greatly enhances
      candidate gene expression pattern accuracy.

PMID- 16964443
TI  - Gene expression study in the juvenile mouse testis: identification of stage
      specific molecular pathways during spermatogenesis.
AB  - A gene expression time course in the juvenile mouse testis was established using
      cDNA microarrays derived from a variety of isolated testis cell types. In
      conjunction with the use of four germ cell-deficient mouse models, a stage and
      cell-type classification over nine time points has been obtained and analyzed for
      differential expression of genes. The expression profiles have been clustered
      into nine groups and subjected to detailed analysis of associated gene ontology.
      This has allowed the correlation of particular cellular processes and functions
      with different expression clusters. Focused analysis of transcripts involved in
      cell number regulation (apoptosis and proliferation) and their spatiotemporal
      expression patterns are presented. The findings indicate that for genes involved
      in both apoptosis and proliferation, several distinct pathways regulating these
      processes are active in somatic and germ cell lineages.

PMID- 16964444
TI  - Nmf11 is a novel ENU-induced mutation in the mouse glycine receptor alpha 1
      subunit.
AB  - Nmf11 is an N-ethyl-N-nitrosourea-induced recessive mouse mutation. In this
      article we show that the mutation is in the gene that encodes the glycine
      receptor alpha 1 subunit (Glra1). The new Glra1 mutation appears to affect
      glycine's inhibitory neurotransmission in the central nervous system (CNS) of the
      nmf11 homozygotes, which suffer from a severe startle disease-related phenotype
      and die by postnatal day 21. The nmf11 mutation involves a C-to-A transition of
      nucleotide 518, which results in the N46K substitution in the long extracellular
      NH(2) terminal or ligand-binding domain of the GLRA1 mature protein. The mutation
      does not result in reduced expression of GLRA1 at the mRNA or protein levels and
      the mutant glycine receptor localizes properly in synaptic sites of nmf11
      homozygotes.

PMID- 16964445
TI  - New ENU-induced semidominant mutation, Ali18, causes inflammatory arthritis,
      dermatitis, and osteoporosis in the mouse.
AB  - Inflammation is a complex cellular and humoral response against trauma and
      infection, and its presence leads to destruction of tissue in humans. The
      mechanisms that initiate inflammatory diseases remain largely unknown because of
      complex interactions between multiple genetic and environmental factors during
      pathogenesis. Animal models for human diseases offer dissection of complex
      pathogenesis by inbred genetic backgrounds and controlled circumstances. In this
      article we report a chemically induced new mutation, Ali18 (Abnormal limb), as a
      mouse model for inflammatory arthritis and dermatitis. Ali18/+ mice exhibit rubor
      and swelling of footpads in hindlimbs in adults. In Ali18/Ali18 mice, the digits
      in forelimbs and hindlimbs and tails were necrotic and/or deformed by severe
      swelling. Histologic analysis revealed infiltration of mixed populations of
      inflammatory cells into bone marrow, peripheral joints, and skin in the affected
      areas of Ali18/Ali18 mice. In addition, generalized osteoporosis-like phenotypes
      were confirmed by dual energy X-ray absorptiometry (DXA), microcomputed
      tomography (muCT), and peripheral quantitative computed tomography (pQCT) in
      homozygous animals. Whereas the Ali18 mutation was mapped to a single locus, the
      phenotype presentation was altered by complex modifier effects from other inbred
      genetic backgrounds. Detailed analysis of the Ali18 phenotype and identification
      of the mutation and its modifier genes may provide molecular insights into the
      complex nature of inflammatory diseases and the relationship between inflammation
      and bone metabolism.

PMID- 16964446
TI  - Gene expression analysis in a canine model of X-linked Alport syndrome.
AB  - Chronic kidney disease (CKD) often culminates in renal failure as a consequence
      of progressive interstitial fibrosis and is an important cause of illness and
      death in dogs. Identification of disease biomarkers and gene expression changes
      will yield valuable information regarding the specific biological pathways
      involved in disease progression. Toward these goals, gene expression changes in
      the renal cortex of dogs with X-linked Alport syndrome (XLAS) were examined using
      microarray technology. Extensive changes in inflammatory, metabolic, immune, and
      extracellular matrix biology were revealed in affected dogs. Statistical analysis
      showed 133 genes that were robustly induced or repressed in affected animals
      relative to age-matched littermates. Altered expression of numerous major
      histocompatibility complex (MHC) molecules suggests that the immune system plays
      a significant role in XLAS. Increased expression of COL4A1 and TIMP-1 at the end
      stage of disease supports the suggestion that expression increases in association
      with progression of fibrosis and confirms an observation of increased COL4A1
      protein expression. Clusterin may function as one of the primary defenses of the
      renal cortex against progressive injury in dogs with XLAS, as demonstrated here
      by increased CLU gene expression. Cellular mechanisms that function during excess
      oxidative stress might also act to deter renal damage, as evidenced by
      alterations in gene expression of SOD1, ACO1, FDXR, and GPX1. This investigation
      provides a better understanding of interstitial fibrosis pathogenesis, and
      potential biomarkers for early detection, factors that are essential to
      discovering more effective treatments thereby reducing clinical illness and death
      due to CKD.

PMID- 16964447
TI  - Diabetic modifier QTLs identified in F2 intercrosses between Akita and A/J mice.
AB  - To identify novel genetic modifiers of type 2 diabetes (T2D), we performed
      quantitative trait loci (QTL) analysis on F(2) progeny of hypoinsulinemic
      diabetic Akita mice, heterozygous for the Ins2 gene Cys96Tyr mutation, and
      nondiabetic A/J mice. We generated 625 heterozygous (F(2)-Hetero) and 338 wild
      type (F(2)-Wild) mice with regard to the Ins2 mutation in F(2) intercross
      progeny. We measured quantitative traits, including plasma glucose and insulin
      concentrations during the intraperitoneal glucose tolerance test (IPGTT), and
      body weight (BW). We observed three significant QTLs in hypoinsulinemic
      hyperglycemic male F(2)-Hetero mice, designated Dbm1, Dbm3, and Dbm4 on
      Chromosomes 6, 14, and 15, respectively. They showed linkage to plasma glucose
      concentrations, with significant maximum logarithm of odds (LOD) scores of 4.12,
      4.17, and 6.17, respectively, all exceeding threshold values by permutation
      tests. In normoinsulinemic normoglycemic male F(2)-Wild mice, Dbm1 on Chromosome
      6 showed linkage to both plasma insulin concentrations and BW, and Dbm2 on
      Chromosome 11 showed linkage to plasma glucose concentrations only, with LOD
      scores of 4.52 and 6.32, and 5.78, respectively. Based on these results, we
      concluded that Dbm1, Dbm2, Dbm3, and Dbm4 represent four major modifier QTLs
      specifically affecting T2D-related traits and that these diabetic modifier QTLs
      are conditional on the heterozygous Ins2 gene mutation and sex to exert their
      modifier functions. Identification of the genes responsible for these QTLs would
      provide new drug development targets for human T2D.

PMID- 16964448
TI  - Improving resectability of hepatic colorectal metastases: expert consensus
      statement by Abdalla et al.

PMID- 16964449
TI  - A 15-year open study on a cohort of West-African out-patients with a chronic
      psychosis.
AB  - BACKGROUND: We wanted to find out if the additional costs of depot neuroleptic in
      comparison to oral medication was justified by a decrease in admission days.
      METHODS: An open study on a cohort of chronic psychotic out-patients (n=45)
      consisting of a retrospective 10-year period on oral medication followed by a
      prospective 5-year period of treatment with haloperidol decanoate. After
      recording socio-demographic characteristics and a DSM-III-R diagnosis, patients
      were assessed before and after the administration of depot neuroleptic with the
      BPRS, the NOSIE, the SDRS and a list of side effects. A semi-structured interview
      was conducted with the patients and their families to ask about the change in
      social relationships with family members and other people after starting the
      depot treatment. Social intervention was limited to involvement of the family in
      the monthly depot medication outpatient clinic and to an explanation of the
      rationale of follow-up treatment and deinstitutionalisation of psychiatric care
      in the village of origin. RESULTS: The number of admission days decreased from an
      average of 100 days a year on oral medication to 5 days a year on depot
      neuroleptic. Patients report a sharp decrease in symptoms paralleled by an
      increase in social functioning over the first 3 months. After 6-9 months this
      pattern stabilised and was maintained over the period from 1 to 5 years whereas
      the dosage was further decreased to an average of 1 cc decanoate or 20 haldol
      equivalents monthly. CONCLUSIONS: This study suggests that depot neuroleptic in
      the context of a public mental health approach is a highly effective and feasible
      treatment for West African patients suffering from a chronic functional
      psychosis.

PMID- 16964450
TI  - How ubiquitous are physical and psychological complaints in young and middle
      adulthood? A longitudinal perspective.
AB  - OBJECTIVES: To investigate continuity and change of self-reported physical and
      psychological complaints in young adults over a period of 20 years. STUDY DESIGN
      AND SETTING: The Zurich Study--a long-term panel survey in psychiatric
      epidemiology--is based on a stratified sample of 591 subjects born in 1958
      (women) and 1959 (men). The sample strata combine SCL-90-R high-scorers and low
      scorers in a 2:1 ratio. Up to now, the Zurich Study has included six interviews
      between 1979 and 1999, i.e. 20 years of life in young adults. We analysed the
      longitudinal frequency data of a variety of physical and psychological
      complaints, as well as information about subjective suffering and use of
      professional help. The analyses utilised on the McNemar's test, the Q-test and
      Markov chain models. RESULTS: Sleep disorders, depression, menstruation,
      backache, headache, stomach and bowel complaints yielded cumulative prevalence
      rates of 80% or higher. Physical and psychological complaints systematically
      differ with respect to the change patterns between 1979 and 1999. Moreover,
      strong differences were found in view of subjective suffering and use of
      professional help. CONCLUSIONS: Even though many self-reported physical and
      psychological complaints are very common in young adulthood, the underlying
      dynamics and the implications largely differ. It seems to be crucial whether
      respondents use somatic glasses or psychological lenses.

PMID- 16964451
TI  - Developing services for the early detection of psychosis: a critical
      consideration of the current state of the art.
AB  - Recent research has attempted to improve the identification of individuals at
      risk of developing schizophrenia to permit targeted early prevention. Two sets of
      criteria, one characterized by a subgroup of 'basic symptoms' [Klosterkotter,
      Hellmich, Steinmeyer, Schultze-Lutter (2001) Arch Gen Psychiat 58:158-164] and
      one by the ultra high-risk model [Miller, McGlashan, Woods, Stein, Driesen,
      Corcoran, Hoffman, Davidson (1999) Psychiatr Q 70:273-287; Yung, McGorry,
      McFarlane, Jackson, Patton, Rakkar (1996) Schizophr Bull 22:283-303], have been
      associated with positive predictive values for later schizophrenia. This paper is
      a critical discussion of these predictive values. In the first part, the paper
      demonstrates that the predictive values of at-risk criteria are mediated by a
      strong enrichment effect and depend considerably on the structure of early
      detection systems. Further, it shows that these predictive values do not apply to
      the general population level, where subclinical psychosis shows high prevalence
      and incidence rates, and that these values may be less predictive in adolescents.
      In the second part, the paper discusses the need for specific sensitization on
      several levels of an early detection system and proposes a selected overview of
      prototypical models already applied in this field.

PMID- 16964452
TI  - Drug usage as a treat to the stability of treatment outcome: a one-year follow-up
      study of adolescent psychiatric patients.
AB  - OBJECTIVE: To examine the stability of treatment outcome one year after discharge
      from an inpatient treatment programme for adolescents with severe behavioural
      problems combined with psychiatric disorders. METHOD: Symptom Check List-90
      Revised (SCL-90 R) ratings were obtained at admission, discharge and one-year
      follow-up for 75 patients. Treatment outcome was determined by calculating
      clinically significant change on the SCL-90 R Global Severity Index (GSI) between
      admission and discharge. Stability of treatment outcome was determined by
      comparing the clinically significant changes on the GSI between admission and
      discharge, and between admission and follow-up. RESULTS: Compared to baseline,
      46.7% of the patients recovered (reliable change was found and their GSI at
      discharge was below the cutoff point for the functional population), 20% improved
      (reliable change was found, but the GSI was still above the cutoff point). For
      the other patients no reliable change was found (12.0%) or they deteriorated
      (21.3%). At follow-up, compared to the base score, 52.0% recovered, 13.3%
      improved, 12.0% showed no reliable change, and 22.7% deteriorated. Although for
      the whole sample no significant change was found between discharge and follow-up,
      some individual patients continued to improve after discharge, while others
      deteriorated. Analyses show that drug usage during the follow-up period is a
      strong predictor for these changes. CONCLUSION: The results indicated that the
      majority of the patients recovered or improved during treatment and this
      treatment outcome was relatively stable at one-year follow-up. However, in a
      minority of patients the treatment results deteriorated during the one-year
      follow-up period. Drug usage turned out to be an important predictor for this
      deterioration.

PMID- 16964453
TI  - Autonomic reactivity in clinically referred children attention
      deficit/hyperactivity disorder versus anxiety disorder.
AB  - This study examined whether children with attention-deficit/hyperactivity
      disorder (ADHD) have lower autonomic nervous system (ANS) activity and show less
      stress reactivity than children with an anxiety disorder. It also explored
      whether such a difference was accounted for by comorbid oppositional defiant
      disorder (ODD) or conduct disorder (CD) in some of the ADHD children. Forty-three
      referred children performed a stress task, during which skin conductance (SCL)
      and heart rate (HR) levels were measured. Results showed that the ADHD group had
      similar SCL responses as the anxiety disorder group, but showed less HR
      reactivity immediately after the stress task. The ADHD with ODD/CD group had a
      slightly higher HR level than the pure ADHD group, but showed similar SCL and HR
      reactivity and recovery. It was concluded that ADHD children have less HR
      reactivity immediately after stress than children with an anxiety disorder, which
      was not accounted for by comorbid ODD/CD symptoms, and which may be related to a
      stronger parasympathetic than sympathetic activation.

PMID- 16964454
TI  - Risk factors for the development of emotional and behavioural problems in
      children born to drug-dependent mothers.
AB  - BACKGROUND: The study of biological and psychosocial risk factors for the
      development of emotional and behavioural problems in children of drug-dependent
      mothers. METHODS: In a sample of 52 children and drug-dependent mothers
      participating in a residential intervention programme emotional and behavioural
      problems were studied in the children by use of the Child Behaviour Checklist
      (CBCL). The Symptom-Checklist Revised (SCL-90-R) served to assess mental problems
      in the mother. Drug exposure during pregnancy, various psychosocial risk factors
      due to the drug-career, and educational status of the mother were assessed by
      maternal interview. A brief assessment of intelligence of the mother was
      included. RESULTS: Among the various biological and psychosocial risk factors,
      maternal mental health problems, maternal educational status, and a small number
      of close social relationships correlated significantly with child outcome
      variables. Multiple regression analyses identified maternal mental health factors
      as the main predictors of child behaviour. CONCLUSIONS: Assisting drug-dependent
      mothers in overcoming the psychosocial sequelae of drug abuse implies also
      assistance to the children in terms of prevention of emotional and behavioural
      problems.

PMID- 16964455
TI  - Disorders of learning and memory processes in a monkey model of Alzheimer's
      disease: the role of the associative area of the cerebral cortex.
AB  - The processes of learning and storage of the results of learning were studied in
      a model of Alzheimer's disease in two groups of rhesus macaques (three
      individuals in each group). Studies were performed after injection of neurotoxins
      (group I) and physiological saline (group II, controls). Two months after
      injections (stage C1), learning parameters were studied in monkeys of both groups
      using a new stimulus discrimination test (filled geometrical figures versus
      outline figures). There were significant differences between the animals of the
      two groups. Learning was hindered in monkeys of group I, with significant
      increases in the learning time (the time to achieve a stable probability of
      correct responding of 0.85) and in the probability of refusals. Monkeys of group
      II showed no learning impairment. Animals were trained to discriminate new
      stimuli (images of two monkeys) six months after injections (stage C3). Learning
      was impaired in animals of group I, such that learning measures had the same
      levels as previously; monkeys of group II showed no learning impairment. Analysis
      of the characteristics of working memory, which is involved in storing the
      results of new learning, was performed at stage C1; monkeys of group I showed
      significant degradation of these measures, with a significant decrease in the
      probability of correct solutions at stage C1 (to a level of 0.5), with some
      increase at stages C2 (at four months) and C3, along with a significant increase
      in the probability of refusals, values being similar at all time points. For
      monkeys of group II, these characteristics showed no degradation. Motor response
      times at stages C1, C2, and C3 were not different for the two groups of monkeys.
      The structural-functional organization of interactions between sensory and
      cognitive processes during learning and the storage of information in working
      memory are discussed, as is the role of the associative areas of the cortex in
      these interactions.

PMID- 16964456
TI  - Mechanisms by which dolphins identify target movement characteristics and their
      technical use in hydrolocation and radiolocation.
AB  - The ability of the localizing system of the dolphin Tursiops truncatus to
      discriminate the dynamic characteristics of an object being located (a radially
      moving target) was studied. Measurements were made of the thresholds of the
      animals' sensitivity to the target speed (2.6 cm/sec) and acceleration (0.6
      cm/sec(2)). For location of a target moving at constant speed, dolphins were
      found to use probe signals consisting of two impulses, while accelerating targets
      were located using probe signals consisting of three impulses. These
      characteristics were used to propose new and highly effective technical methods
      for hydrolocation and radiolocation.

PMID- 16964457
TI  - The effects of vibration on the baseline spike activity of neurons in the
      superior vestibular nucleus.
AB  - The characteristics of the baseline spike activity of neurons in the superior
      vestibular nucleus of rats were studied after exposure to vibration for five, 10,
      and 15 days using a computerized method for recording and analyzing interspike
      intervals. The distributions of neurons in terms of their regularity, their
      dynamic types, and the modalities of their interspike interval histograms were
      assessed. In intact animals, the mean spike frequency was 14.0 +/- 1.4 Hz.
      Changes in the main measures were seen at different durations of exposure to
      vibration, along with a significant increase in the mean neuron spike frequency.
      The results demonstrate changes in the level of the functional state of neurons
      in the superior vestibular nucleus after exposure to vibration. The
      characteristics and significance of the results are discussed.

PMID- 16964458
TI  - Long-term potentiation in the hippocampus in conditions of inhibition of caspase
      3: analysis of facilitation in paired-pulse stimulation.
AB  - Treatment of hippocampal slices with the caspase-3 inhibitor Z-DEVD-FMK led to a
      decrease in the magnitude of long-term potentiation (LTP), which developed over
      time. Testing with paired stimuli separated by an interval of 70 msec showed that
      after caspase-3 inhibition, as compared with control slices, the second response
      in the pair showed no increase in amplitude in conditions of LTP. In these
      conditions, the magnitude of LTP depended on differences in the amplitudes of the
      first and second responses before induction of LTP. LTP was absent in slices with
      initially highly efficient afferent stimulation and correspondingly low levels of
      facilitation in paired-pulse stimulation. It is suggested that inhibition of
      caspase-3 prevents the structural rearrangements in LTP associated with the
      involvement of new synapses and neurons in the response.

PMID- 16964460
TI  - Changes in the structure of neuronal connections in the visual cortex of cats
      with experimentally induced bilateral strabismus.
AB  - The spatial distribution of neuronal connections in cortical field 17 was studied
      in cats with experimentally induced bilateral convergent strabismus on postnatal
      days 10-14. Horseradish peroxidase was applied microiontophoretically to
      individual columns of neurons in fields 17 and 18 and retrograde-labeled cells
      were identified in both hemispheres. Increases and decreases in the extent of
      intra-hemisphere connections were seen in the mediolateral direction (projections
      of the horizontal meridian of the visual field). Most columns showed increases in
      inter-hemisphere connections in this same direction, which may support the more
      reliable unification of the two visual hemifields. In addition, some columns
      showed increases in intra-and inter-hemisphere connections in the rostrocaudal
      direction (projections of the vertical meridian). Thus, bilateral strabismus
      induced during the critical period of development leads to changes in the
      structure of both intra-hemisphere and inter-hemisphere connections of individual
      cortical columns in fields 17 and 18.

PMID- 16964459
TI  - Cytophysiology of spiny stellate cells in the striate cortex and their role in
      the excitatory mechanisms of intracortical synaptic circulation.
AB  - Spiny stellate cells (SS) are an exclusive category of cortical interneurons and
      are the major component of intracolumnar, lateral, and callosal excitation of
      pyramidal and non-pyramidal neurons in the neocortex. The axons of SS make
      contact with the apical dendrites of pyramidal neurons, forming cartridge-type en
      passant synapses with them. SS establish recurrent connections with inhibitory
      interneurons and other SS, and also form autapses contacts. SS subtypes were
      identified and descriptions of their structure, neurochemical specialization, and
      spatial organization in the human and animal neocortex are provided. The results
      of our own studies, along with published data, are used to form a critical
      analysis of current concepts of the histophysiology of recurrent excitatory and
      inhibitory neurocirculation in cortical modules.

PMID- 16964461
TI  - Effects of streptokinase on the development of rat cerebral cortical cells in
      vitro.
AB  - The aim of the present work was to study the effects of streptokinase (SK) on the
      ultrastructure of the cellular elements of the cerebral cortex of neonatal rats
      in vitro. Three series of cultures were used: cultures maintained in DMEM
      enriched with 15% fetal calf serum (control 1), some transferred to minimal
      nutritive medium containing only 0.5% serum (control 2), and some supplemented
      with SK (2000 MU/ml) (experimental). Addition of SK to the nutritive medium
      prevented a decrease in the viability of cells in a mature (14 days) dissociated
      culture from the neocortex of rat pups aged 1-2 days induced by transfer of the
      cultures to medium lacking serum proteins. The action of SK on 7-day cultures
      enhanced the loss of cell viability. Electron microscopy studies of organotypic
      cultures showed that at this concentration, SK prevented the development of
      destructive changes of astrocytes, oligodendrocytes, and neurons induced in
      explants by serum protein deficiency. Neurons showed an abundance of
      mitochondria, some of which had few cristae. Signs of destruction affected only
      the nuclei of neurons. After exposure to SK for 48 h, oligodendrocytes were
      activated (they contained an abundance of myelin-like bodies), with degradation
      of most astrocytes (surviving examples showing nuclear hyperchromicity). Neurons
      were resistant to these effects.

PMID- 16964462
TI  - Structural-functional reorganization of nonapeptidergic neurosecretory
      hypothalamic nuclei in experimental acute pancreatitis.
AB  - Structures of the pancreas and magnocellular (supraoptic and paraventricular)
      nuclei of the hypothalamus of adult male rats were studied in conditions of acute
      pancreatitis at the light and electron microscopic levels. Histo-and organotypic
      changes in the parenchymatous and stromal elements of the pancreas were analyzed
      simultaneously with cytological assessment of the state of the nonapeptidergic
      neurosecretory centers of the hypothalamus. Blockade of the release of
      hypothalamic nonapeptides was found to occur at the level of axovasal complexes,
      and this aggravated the outcome of destructive and necrobiotic changes in the
      pathologically altered organ.

PMID- 16964463
TI  - Immunocytochemical characteristics of neurons in the stellate ganglion of the
      sympathetic trunk in mice during postnatal ontogenesis.
AB  - The neurotransmitter composition of neurons in the stellate ganglion of mice of
      different ages (neonatal and aged 10, 20, 30, and 60 days) was studied using an
      immunocytochemical method. Most of the neurons in the mice of these age groups
      contained tyrosine hydroxylase (TH). Most choline acetyltransferase (CAT)
      positive neurons in neonatal and 10-day mice were also TH-positive. From birth
      and at all subsequent ages, there were increases in the proportion of cells
      contained TH and neuropeptide Y. The proportion of neurons containing vasoactive
      intestinal peptide and CAT increased to 10 days of life and then decreased.
      Somatostatin-and galanin-positive neurons were absent from all animals.
      Maturation of the set of neurotransmitters in stellate ganglia was complete by
      age two months.

PMID- 16964464
TI  - Immunocytochemical detection of brain neurons using the selective marker NeuN.
AB  - The aim of the present work was to develop optimal protocols for
      immunocytochemical reactions for nuclear protein NeuN for light and laser
      confocal microscopy which avoid the thermal antigen demasking procedure, which
      degrades the state of the tissue and requires use of expensive adhesive-coated
      slices. Maximal antigen retention was obtained after fixation in zinc-formalin
      and Bouin's fluid (maximum one day). Two protocols are proposed allowing the
      thermal demasking procedure to be avoided during detection of neuron marker NeuN
      on paraffin sections examined by light and confocal microscopy.

PMID- 16964465
TI  - Possible regulation of venous outflow from deep brain structures.

PMID- 16964466
TI  - Asymmetry of the amplitude-time properties of directed saccades in monkeys
      depending on the complexity of the spatial scheme of visual stimulation.
AB  - Three Macaca rhesus monkeys were used for studies of the performance of visually
      evoked saccades in single-step changes in the position of a stimulus using
      standard schemes for presentation of GAP-OVERLAP stimuli. Two spatial schemes
      were used: presentation of stimuli along the horizontal meridian (one
      dimensional) and presentation of stimuli within a rectangular area of the visual
      field (two-dimensional). Asymmetrical foci of short-and long-latency saccades
      were found in the visual field. Dispersion factor analysis demonstrated that the
      dimensionality factor (one-dimensional versus two-dimensional stimulation
      schemes) had greater effects on the latent period of saccades than the
      lateralization factor (presentation on the left or right sides of the gaze
      point). The precision of the performance of visually evoked saccades decreased
      with increases in its eccentricity in both spatial stimulation schemes.

PMID- 16964467
TI  - Regional characteristics of electrical responses (in the band 1-225 Hz) in the
      cerebral cortex to conditioned stimuli in operant conditioning.
AB  - Power spectra of short-term (less than 1 sec) electrical responses to conditioned
      stimuli were studied over the frequency range 1-225 Hz in dogs during food
      related operant conditioning. These spectra demonstrated regional characteristics
      in terms of energy levels and frequency composition. Responses were more marked
      in the visual and parietal areas of the left hemisphere. Power in responses to a
      differential stimulus were significantly lower than with responses to positive
      stimuli, mainly because of the high-frequency range (80-225 Hz); energy levels in
      these two situations were similar during prestimulus intervals. The frequency
      composition of responses was defined by a series of discrete frequencies in the
      gamma (30-80 Hz) and high-frequency ranges.

PMID- 16964468
TI  - Effect of whisker removal on defensive behavior in rats during early ontogenesis.
AB  - The effects of restriction of sensory afferentation in rats by vibrissectomy
      performed daily on days 9 to 20 of life on the formation of defensive reactions
      in early postnatal ontogenesis were studied. Vibrissectomized and control rat
      pups were assessed in terms of the extent of motor defensive reactions in
      response to touching the skin from days 10 to 18 of life, the duration of the
      freezing reaction at age 20 days, and behavior in the open field at age 25 days.
      Vibrissectomized rat pups showed the following significant differences from
      controls: a decrease in the extent of early withdrawal from a potentially
      dangerous stimulus (at age 12 and 13 days), a decrease in the duration of the
      freezing reaction, and decreases in that extents of the flight reaction and
      emotional reactivity in the open field test.

PMID- 16964469
TI  - Modulation of neuron activity in the basal forebrain of the rat related to the
      outcome of food-procuring movements.
AB  - Neuron activity was recorded from the basal forebrain of rats, including the
      mixed area of the ventral pallidum, substantia innominata, and mid part of
      Meynert's nucleus. The base of the forebrain was found to contain neurons (40% of
      all neurons recorded) which altered their activity on acquisition of a food
      procuring skill in conditions of free behavior, depending on the outcome of the
      acquired movement reaction. The discharge frequencies of these cells increased
      when the animal obtained food from the feeder. When the rat was unable to procure
      the food, the discharge frequency of these cells either remained constant or
      decreased. Most of the neurons (57.1% of all neurons showing modifications)
      demonstrated modulation of their activity towards the end of the food-procuring
      movement, but before it was completed. A smaller proportion of the cells (35.7%)
      changed their activity after food was retrieved from the feeder.

PMID- 16964470
TI  - Recovery of a motor skill in rats with different forelimb preferences after
      lesioning of the caudate nucleus: the role of intense training.
AB  - The aim of the present work was to study the effects of training on the
      restoration of a lateralized motor skill (a food-procuring forelimb movement) in
      Wistar rats (n = 83) after lesioning of the caudate nucleus in conditions of
      infrequent testing and intensive retraining. On the basis of the training
      results, the rats were divided into those preferring the right (right-handers) or
      left (left-handers) limb. Testing was followed by lesioning of the head of the
      caudate nucleus on the side contralateral to the preferred paw. Animals with
      identical initial preferences were then divided into two groups: an infrequently
      tested group in which recovery of the skill was tested once weekly for five
      months, and an intensive retraining group, in which experiments were performed 3
      4 times weekly, again for five months. After surgery, animals had to perform the
      food-procuring skill only with the "impaired" paw. Differences in the recovery of
      the skill were seen in animals with different limb preferences both in conditions
      of spontaneous recovery and in those recovering with training. Overall, animals
      with lesions of the left caudate nucleus (right-handers) showed better recovery
      than animals with lesions of the right caudate nucleus (left-handers) in both
      spontaneous recovery and in recovery with training. These findings suggest that
      the central neural mechanisms of recovery of a lateralized motor skill after
      unilateral lesioning of the caudate nucleus are different after lesions to the
      right and left hemispheres.

PMID- 16964471
TI  - Cross-interval histograms for analysis of brain electrical activity.
AB  - A method for constructing cross-interval histograms for time-localized EEG
      fragments of particular types is described. The basic principles of the method
      are presented. Examples of cross-interval histograms constructed for EEG extrema
      and their derivatives are presented. Cross-interval histograms were shown to
      include peaks, troughs, and other features. Cross-interval histogram and cross
      correlation histograms are compared. The method yields qualitatively new data on
      interactions between changes in biopotentials in different areas of the brain and
      allows rapid processes to be studied.

PMID- 16964472
TI  - Solution to geometric chemistry challenge.

PMID- 16964473
TI  - Monitoring lipase-catalyzed butterfat interesterification with rapeseed oil by
      Fourier transform near-infrared spectroscopy.
AB  - This work demonstrates the application of FT-NIR spectroscopy in order to monitor
      the enzymatic interesterification process for butterfat modification. The
      reactions were catalyzed by Lipozyme TL IM at 70 degrees C for the blend of
      butterfat/rapeseed oil (70/30, w/w) in a packed-bed reactor. The blend and
      interesterified fat samples were measured in liquid form at 70 degrees C by
      transmission mode-based FT-NIR over the spectral region 12000-4000 cm-1. The
      calibration of FT-NIR for conversion degree (evaluated by the triglyceride
      profile, which was represented by the triglyceride peak ratio) and solid fat
      content (SFC) of the interesterified products was carried out using partial least
      squares (PLS) regression. Good correlations were observed between the NIR spectra
      and ln (peak ratio), and between the NIR spectra and the SFC at 5 degrees C over
      the spectral range 5269-4513 cm-1. Overall, transmission-mode FT-NIR spectroscopy
      performed at 70 degrees C yielded conditions close to those used during the
      interesterification process, implying that this method could be used to control
      the enzymatic interesterification process online.

PMID- 16964475
TI  - Single-detector micro-electro-mechanical scanning grating spectrometer.
AB  - A compact, robust grating spectrometer based on an optimised micro-electro
      mechanical grating mirror component has been developed, built, and characterised.
      The application of an oscillating reflection grating micro-mirror component as
      scanning dispersive element in a modified Czerny-Turner monochromator layout
      enables the design of compact grating spectrometers capable of acquiring full
      spectra using a single detector element. Designed for a wavelength range between
      1200 and 1900 nm, the spectrometer features a spectral resolution of 10 nm with
      wavelength stability better than +/-0.5 nm. One-hundred scan spectra can be
      acquired in less than one second, or spectral changes can be monitored at time a
      resolution of less than 10 ms. In combination with a fibre-optic interface and a
      typical weight of less than 1 kg, this makes this novel type of fully portable
      micro-electro-mechanical near-IR scanning spectrometer an interesting alternative
      to existing spectrometers and opens a range of new applications, in particular
      the detection of major and minor components in the near-IR.

PMID- 16964474
TI  - Comparative study between a commercial and a homemade capillary electrophoresis
      instrument for the simultaneous determination of aminated compounds by induced
      fluorescence detection.
AB  - The performance of two capillary electrophoresis (CE) instruments, one commercial
      and one homemade device, were compared for the determination of derivatised
      aminated compounds with fluorescein isothiocyanate (FITC). The commercial CE
      system first uses an argon ion laser as excitation source; the homemade CE device
      uses an inexpensive blue-light-emitting diode (LED) as the light source and a
      charge-coupled device (CCD) as the detection system. After fine optimisation of
      several separation parameters in both devices, a co-electroosmotic flow CE
      methodology was achieved in coated capillary tubing with 0.001% hexadimetrine
      bromide (HDB), and 50 mmol L-1 sodium borate at pH 9.3 with 20% 2-propanol for
      the determination of several amines and aminoacids. Analytical performances,
      applicability in beer samples and other aspects such as cost or potential for
      miniaturization have been compared for both devices.

PMID- 16964476
TI  - [Raynaud phenomenon in dermatology : Part 2: therapy].
AB  - While primary Raynaud phenomenon (RP) only rarely leads to complications,
      secondary RP when associated with systemic sclerosis (SSc) frequently results in
      necrosis, ulcers or even gangrene. Therefore timely therapeutic intervention is
      required. Management of RP includes physical therapy, avoidance of triggers, and
      a variety of medications, depending on the disease severity. On the basis of
      published studies and of our own experience we suggest: a) for primary and
      uncomplicated secondary RP, calcium channel blockers in adequate doses; b) for
      SSc-associated secondary RP with hypertension, cardial or renal involvement,
      drugs which interfere with angiotensin; c) in case of concomitant depression,
      exploitation of the vasodilatory effects of serotonin reuptake inhibitors, d) in
      presence of ulcers or marked trophic alterations, intravenous administration of
      iloprost, e) for recalcitrant cases and endangered digits, sildenafil, f) for
      prevention of severe relapses, the endothelin-receptor antagonist bosentan. The
      drugs mentioned in c-f are not approved for RP and used off-label. In patients
      with secondary SSc-associated RP, timely therapy can reduce the percentage of
      complications such as ulcers or amputations. In addition, timely treatment of RP
      possibly retards ensuing fibrotic processes.

PMID- 16964477
TI  - [Current recommendations for the use of SCIT and SLIT].
AB  - Allergen specific immunotherapy (SIT) is the only potentially curative treatment
      of IgE mediated allergic diseases. To ensure its effective use, many requirements
      must be met before and during therapy. Before starting immunotherapy, informed
      consent should be obtained, along with the consideration of the indications and
      contraindications. SIT should be prescribed and administered only by physicians
      with experience in allergic disease who are qualified to manage severe
      anaphylactic reactions. The clinical symptoms and the age of the patients
      determine the route of application, choice of allergen extracts and the duration
      of treatment. Numerous products and protocols facilitate an individualised
      therapy.

PMID- 16964478
TI  - Exercise capacity and oxygen recovery half times of skeletal muscle in patients
      with fibromyalgia.

PMID- 16964479
TI  - Premature myocardial infarction in a young woman with systemic lupus
      erythematosus.

PMID- 16964480
TI  - [Pathophysiology and pathomorphology of osteoporosis].
AB  - Osteoporosis is a disease that leads to fragility fractures due to loss of bone
      mass and bone microstructure. This review presents an update on the fundamental
      pathophysiologic and pathomorphologic mechanisms of bone loss situations.
      Pathomorphologic characteristics such as perforations and microcallus formations
      are explained. The physiologic relevance of the remodeling process as well as its
      control by local-paracrine, systemic-endocrine and central-neural signaling
      pathways is discussed. Furthermore the role of hormones such as estrogen, FSH and
      leptin, of transcription-factors such as Runx2 and osterix and as well as that of
      the wnt signaling pathway for bone cell differentiation and function is
      presented. On the basis of current knowledge osteoporosis can be diagnosed,
      treated and fractures can be prevented. However, it is likely that new and even
      more effective diagnostic and therapeutic strategies will emerge as our
      understanding of the remodeling process that controls osteoblast and osteoclast
      function increases.

PMID- 16964482
TI  - Apoptosis of neuronal cells induced by serum of patients with acute brain injury:
      a new in vitro prognostic model.
AB  - OBJECTIVE: To investigate whether serum draining from the jugular bulb of
      patients with traumatic or haemorrhagic brain injury induced apoptosis of
      neuronal PC12 cells in vitro and whether the apoptotic rate correlated with
      patients' outcome at 6 months. DESIGN AND SETTING: Prospective clinical
      investigation in a 21-bed intensive care unit (ICU) in a university hospital.
      PATIENTS: Seventy patients who had suffered from acute brain injury requiring
      intensive care. INTERVENTIONS: Jugular bulb vein and systemic samples were
      obtained on admission to the ICU and after 48 h. PC12 cells were incubated in the
      presence of 10% of heat-inactivated patient's sera and apoptotic rate was
      determined by flow cytometry using annexin V and 7-aminoactinomycin D. RESULTS:
      Regional serum draining from the lesions induced higher early apoptosis of PC12
      cells than systemic serum. Early apoptotic rate, Glasgow coma score, APACHE II
      score and the presence of pupil abnormalities were associated with mortality at 6
      months in univariate statistical analyses. In logistic regression analysis only
      early apoptotic rate was an independent factor associated with mortality at 6
      months (odds ratio: 1.502, 95% CI 1.2-1.9; p<0.001). The final model has a
      sensitivity of 82.4% and a specificity of 84.8% for predicting death within 6
      months. CONCLUSIONS: We developed a simple and reproducible in vitro model for
      predicting outcome in patients with traumatic or haemorrhagic brain injury that
      survived in the early phase. Our in vitro model combined with clinical and
      radiological measurements might improve the value of prognostic models to predict
      acute brain injury patients' outcome.

PMID- 16964481
TI  - The genetics of systemic lupus erythematosus: understanding how SNPs confer
      disease susceptibility.
AB  - The identification of genes for autoimmune diseases is just the first step
      towards our understanding of disease pathogenesis. In investigating how
      mutations, deletions or other types of polymorphic defects occur, it is important
      to determine the pathways and the mechanisms through which susceptibility leads
      to disease. In this review I touch on three examples of studies that have
      attempted to understand the mechanisms of genetic susceptibility in three genes
      identified recently for systemic lupus erythematosus: PDCD1, PTPN22 and IRF5. We
      are just beginning to comprehend and much needs to be done.

PMID- 16964483
TI  - Increased colorectal permeability in patients with severe sepsis and septic
      shock.
AB  - OBJECTIVE: To develop a method for the assessment of colorectal permeability in
      septic patients. DESIGN AND SETTING: Observational study in ICUs at two
      university hospitals. PARTICIPANTS: Nine patients with septic shock and abdominal
      focus of infection, 7 with severe sepsis and pulmonary focus and 8 healthy
      subjects. MEASUREMENTS AND RESULTS: Colorectal permeability was assessed as the
      initial appearance rate of (99m)Tc-DTPA in plasma after instillation into the
      rectal lumen and as the cumulative systemic recovery at 1h. To calculate the
      latter, volume of distribution and renal clearance of (99m)Tc-DTPA was estimated
      by an i.v. bolus of (51)Cr-EDTA. The initial rate of permeability was increased
      in patients with septic shock and severe sepsis compared with controls [29.0 (3.7
      83.3), 20.6 (3.6-65.5) and 6.0 (2.2-9.6)cpm ml(-1)min(-1), respectively, p<0.05)]
      with a positive linear trend (r (2)=0.27, p=0.01) and correlated to L-lactate
      concentrations in the rectal lumen (r (2)=0.39, p<0.05). The cumulative
      permeability was also increased in patients with septic shock and severe sepsis
      compared with controls [2.07 (0.05-15.7), 0.32 (0.01-1.2) and 0.03 (0.01-0.06)
      per thousand, respectively, p<0.01] and correlated to the initial permeability
      rate (r (2)=0.26, p=0.01). CONCLUSIONS: In septic patients, the systemic recovery
      of a luminally applied marker of paracellular permeability was increased and
      related to the luminal concentrations of L-lactate and possibly to disease
      severity. This suggests that the assessment of colorectal permeability by
      systemic recovery of (99m)Tc-DTPA is valid and that metabolic dysfunction of the
      mucosa contributes to increased permeability of the large bowel in patients with
      severe sepsis and septic shock.

PMID- 16964484
TI  - Spinal muscular atrophy with respiratory disease (SMARD): an ethical dilemma.

PMID- 16964485
TI  - Respiratory failure in infants due to spinal muscular atrophy with respiratory
      distress type 1.
AB  - BACKGROUND: Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is
      a rare autosomal recessive neuromuscular disease of unknown prevalence
      characterized by degeneration of anterior horn alpha-motoneurons and manifesting
      in the first 6months of life as life-threatening irreversible diaphragmatic
      paralysis associated with progressive symmetrical muscular weakness (distal lower
      limbs mainly involved), muscle atrophy, and peripheral sensory neuropathy.
      SETTING: Pediatric intensive care unit of tertiary care hospital. PATIENTS: We
      present two new cases of SMARD1 and report two new mutations in the gene IGHMBP2
      which encodes immunoglobulin mu-binding protein 2 on chromosome 11q13.
      CONCLUSIONS: SMARD1 is a poor-prognosis disease that should be considered when
      acute respiratory insufficiency, of suspected neuromuscular or unclear cause,
      develops during the first 6months of life. Diaphragmatic paralysis, manifesting
      as dyspnea and paradoxical respiration, is the most prominent presenting sign and
      diaphragmatic motility should be investigated early by fluoroscopy or ultrasound.
      Electromyography and nerve conduction studies revealing peripheral motor and
      sensory neuropathy then suggest the diagnosis which should be confirmed by
      genetic analysis.

PMID- 16964486
TI  - Developmental dysplasia of the hip in cerebral palsy--surgical treatment.
AB  - Developmental dysplasia of the hip (DDH) in cerebral palsy (CP) is very rare, and
      very little clinical data is available. We have analysed the results of open
      reduction of the hip (Howorth), acetabuloplasty (Salter, Pemberton), pelvic
      osteotomy (Chiari) and femoral osteotomy in the treatment of the DDH in CP
      patients. Radiographic assessment was based on the Severin grading classification
      system and measurements of migration percentage (MP) before and after surgery.
      Clinical results were analysed using the Ponsetti classification system in
      ambulatory patients. A total of 45 hips in 31 patients were treated surgically.
      The average age of the patients was 5.2 years (range: 2-16 years). The average
      follow-up was 9.6 years (range: 3-28 years). Analysis of the radiographic results
      according to Severin placed 35 hips (77.8%) in groups 1 and 2 and ten hips
      (22.2%) in groups 3 and higher. The average preoperative MP value was 78.7% and
      the average postoperative MP was 15.2%. Redislocation occurred in three hips.
      Clinical results were disappointing: based on Ponsetti assessment 14 hips (36.8%)
      were classified in the first three groups and 24 hips (63.2%) in the last three
      groups. This analysis suggests that these surgical procedures could be applied in
      treating DDH in CP.

PMID- 16964487
TI  - Impaction allograft with cement for the revision of the femoral component. A
      minimum 39-month follow-up study with the use of the Exeter stem in Asian hips.
AB  - We report the results of impaction bone grafting of the femoral side in revision
      total hip arthroplasty in Asian hips (South Korean patients) in which the surgery
      was performed with the use of the Exeter stem. The minimum follow-up was 39
      months (mean, 48.4; range, 39-66). There was subsidence of the cement-graft
      interface (<1 mm) in three hips (5%), of the stem-cement interface (<1 mm) in 12
      hips (21%) and of the stem-cement interface (1-2 mm) in 14 hips (25%). Five hips
      (9%) developed intraoperative femoral fracture and two hips (4%) femoral
      perforation in revision. The complications of femoral fracture and subsidence did
      not have an adverse effect on the final clinical outcomes. The impaction of fresh
      frozen allograft and use of a cemented, polished, tapered stem (Exeter stem) were
      also successful with good clinical and radiographic outcomes in our study of
      Asian hips (South Korean patients). However, we used smaller stems than the usual
      ones used for Western patients because of the smaller femur sizes.

PMID- 16964488
TI  - Quantitative and qualitative characterization of vascularization and hemodynamics
      in head and neck tumors with a 3D magnetic resonance time-resolved echo-shared
      angiographic technique (TREAT)--initial results.
AB  - The purpose of this paper is to characterize and quantify the vascularization and
      hemodynamic characteristics of head and neck tumors (HNT) with a dynamic 3D time
      resolved echo-shared angiographic technique (TREAT) using the regular contrast
      agent (CA) bolus. Sixteen patients with HNT underwent 3D-TREAT during the CA
      administration on a 1.5-T magnetic resonance (MR) scanner. Using a parallel
      imaging acceleration factor of 2, 20 3D data sets at a temporal resolution of 2.3
      s/frame were acquired. The quality of tumor delineation, vascularization type,
      and enhancement pattern were evaluated. Quantitative assessment included
      measurement of the contrast-to-noise ratio (CNR), determination of signal
      intensity-over-time (SIT) curves, time-to-peak enhancement within the carotid
      arteries and the tumor, and the delay between both. TREAT was compared to
      conventional digital subtraction angiography (DSA) in six patients. Tumor
      delineation with TREAT was very good or good in 11/16 patients, and better with
      TREAT than with DSA in 3/6 cases. The CNR was significantly different for glomus
      tumors versus hypovascularized malignant tumors with TREAT (p=0.0001), but not on
      T1-weighted gradient echo (T1w GE) images. Qualitative assessment of tumor
      vascularization on dynamic TREAT shows good correlation (r=0.75) to quantitative
      SIT curves. We conclude that TREAT imaging permits the characterization of tumor
      vascularity and holds promise as a supplementary diagnostic tool in the
      differential diagnosis of HNT.

PMID- 16964489
TI  - Pulmonary nodule detection with digital projection radiography: an ex-vivo study
      on increased latitude post-processing.
AB  - To evaluate increased image latitude post-processing of digital projection
      radiograms for the detection of pulmonary nodules. 20 porcine lungs were inflated
      inside a chest phantom, prepared with 280 solid nodules of 4-8 mm in diameter and
      examined with direct radiography (3.0x2.5 k detector, 125 kVp, 4 mAs). Nodule
      position and size were documented by CT controls and dissection. Four intact
      lungs served as negative controls. Image post-processing included standard tone
      scales and increased latitude with detail contrast enhancement (log-factors 1.0,
      1.5 and 2.0). 1280 sub-images (512x512 pixel) were centred on nodules or
      controls, behind the diaphragm and over free parenchyma, randomized and presented
      to six readers. Confidence in the decision was recorded with a scale of 0-100%.
      Sensitivity and specificity for nodules behind the diaphragm were 0.87/0.97 at
      standard tone scale and 0.92/0.92 with increased latitude (log factor 2.0). The
      fraction of "not diagnostic" readings was reduced (from 208/1920 to 52/1920). As
      an indicator of increased detection confidence, the median of the ratings behind
      the diaphragm approached 100 and 0, respectively, and the inter-quartile width
      decreased (controls: p<0.001, nodules: p=0.239) at higher image latitude. Above
      the diaphragm, accuracy and detection confidence remained unchanged. Here, the
      sensitivity for nodules was 0.94 with a specificity from 0.96 to 0.97 (all
      p>0.05). Increased latitude post-processing has minimal effects on the overall
      accuracy, but improves the detection confidence for sub-centimeter nodules in the
      posterior recesses of the lung.

PMID- 16964490
TI  - Correlation between initial chromatid damage and survival of various cell lines
      exposed to heavy charged particles.
AB  - The biophysical characteristics of heavy ions make them a rational source of
      radiation for use in radiotherapy of malignant tumours. Prior to radiotherapy
      treatment, a therapeutic regimen must be precisely defined, and during this stage
      information on individual patient radiosensitivity would be of very great medical
      value. There are various methods to predict radiosensitivity, but some shortfalls
      are difficult to avoid. The present study investigated the induction of chromatid
      breaks in five different cell lines, including one normal liver cell line (L02),
      exposed to carbon ions accelerated by the heavy ion research facility in Lanzhou
      (HIRFL), using chemically induced premature chromosome condensation (PCC).
      Previous studies have reported the number of chromatid breaks to be linearly
      related to the radiation dose, but the relationship between cell survival and
      chromatid breaks is not clear. The major result of the present study is that
      cellular radiosensitivity, as measured by D0, is linearly correlated with the
      frequency of chromatid breaks per Gy in these five cell lines. We propose that
      PCC may be applied to predict radiosensitivity of tumour cells exposed to heavy
      ions.

PMID- 16964492
TI  - Synovial sarcoma of primary bone origin: a rare case in a rare site with atypical
      features.
AB  - Synovial sarcoma of bone origin is extremely rare and difficult to diagnose. We
      present a case in which the lesion arose in the cortex of the distal tibia. It
      showed heterogeneous intermediate signal intensity on T1-weighted images and
      heterogeneous intermediate to low signal intensity on T2-weighted images with
      heterogeneous contrast enhancement on MRI. The lesion was confirmed as synovial
      sarcoma using a combination of histological and molecular genetic studies.

PMID- 16964491
TI  - An internal clock generates repetitive predictive saccades.
AB  - Previously we demonstrated the presence of a behavioral phase transition between
      reactive and predictive eye tracking of alternating targets. Prior studies of
      repetitive movements have proposed that an "internal clock" is the neural
      mechanism by which interval timing is achieved. In the present report we tested
      whether predictive oculomotor (saccade) tracking is based on an internal time
      reference (clock) by examining the effect of transient perturbations to the
      periodic pacing stimulus. These perturbations consisted of altering the timing of
      the stimulus (abruptly increasing or decreasing the inter-stimulus interval) or
      extinguishing the targets altogether. Although reactive tracking (at low pacing
      rates) was greatly affected by these timing perturbations, once predictive
      tracking was established subjects continued to time their eye movement responses
      at the pre-existing rate despite the perturbation. As expected from certain clock
      models, inter-stimulus intervals for predictive tracking followed Weber's law and
      the scalar property (timing variability increases in proportion to interval
      duration), but this was not true for reactive tracking. In addition, the
      perturbation results show that subjects can establish an internal representation
      of target pacing (the internal clock) in as little as two eye-movement intervals,
      which suggests that this mechanism is relevant for real-world situations. These
      findings are consistent with the presence of an internal clock for the generation
      of these predictive movements, and demonstrate that the neural mechanism
      responsible for this behavior is temporally accurate and flexible.

PMID- 16964493
TI  - The lipopeptides mycosubtilin and surfactin enhance spreading of Bacillus
      subtilis strains by their surface-active properties.
AB  - The colonizing behaviour and the pellicle formation of Bacillus subtilis strains
      producing different families of lipopeptides were evaluated under several
      cultural conditions. The pattern of lipopeptides produced determined the
      architecture of the colony on a swarming medium as well as the flotation and the
      thickness of the pellicle formed at the air/liquid interface. The overproduction
      of mycosubtilin, a lipopeptide of the iturin family, led to increased spreading
      but had no effect on pellicle formation. A physico-chemical approach was
      developed to gain an insight into the mode of action of the biosurfactants
      facilitating the colonization. A relationship between surface tension of the
      culture medium and spreading of a lipopeptide non-producing strain, B. subtilis
      168, was established. Goniometry was used to highlight the modification of the in
      situ wettability in the area where spreading was enhanced. On a solid medium, co
      cultures of a surfactin producing with other strains showed a diffusion ring of
      the surfactin around the colony. This ring characterized by a higher wettability
      favoured the propagation of other colonies.

PMID- 16964494
TI  - Diversity of intersegmental auditory neurons in a bush cricket.
AB  - Various auditory interneurons of the duetting bush cricket Ancistrura
      nigrovittata with axons ascending to the brain are presented. In this species,
      more intersegmental sound-activated neurons have been identified than in any
      other bush cricket so far, among them a new type of ascending neuron with
      posterior soma in the prothoracic ganglion (AN4). These interneurons show not
      only morphological differences in the prothoracic ganglion and the brain, but
      also respond differently to carrier frequencies, intensity and direction. As a
      set of neurons, they show graded differences for all of these parameters. A
      response type not described among intersegmental neurons of crickets and other
      bush crickets so far is found in the AN3 neuron with a tonic response, broad
      frequency tuning and little directional dependence. All neurons, with the
      exception of AN3, respond in a relatively similar manner to the temporal patterns
      of the male song: phasically to high syllable repetitions and rhythmically to low
      syllable repetitions. The strongest coupling to the temporal pattern is found in
      TN1. In contrast to behavior the neuronal responses depend little on syllable
      duration. AN4, AN5 and TN1 respond well to the female song. AN4 (at higher
      intensities) and TN1 respond well to a complete duet.

PMID- 16964495
TI  - Olfactory conditioning of proboscis activity in Drosophila melanogaster.
AB  - Olfactory learning and memory processes in Drosophila have been well investigated
      with aversive conditioning, but appetitive conditioning has rarely been
      documented. Here, we report for the first time individual olfactory conditioning
      of proboscis activity in restrained Drosophila melanogaster. The protocol was
      adapted from those developed for proboscis extension conditioning in the honeybee
      Apis mellifera. After establishing a scale of small proboscis movements necessary
      to characterize responses to olfactory stimulation, we applied Pavlovian
      conditioning, with five trials consisting of paired presentation of a banana
      odour and a sucrose reward. Drosophila showed conditioned proboscis activity to
      the odour, with a twofold increase of percentage of responses after the first
      trial. No change occurred in flies experiencing unpaired presentations of the
      stimuli, confirming an associative basis for this form of olfactory learning. The
      adenylyl cyclase mutant rutabaga did not exhibit learning in this paradigm. This
      protocol generated at least a short-term memory of 15 min, but no significant
      associative memory was detected at 1 h. We also showed that learning performance
      was dependent on food motivation, by comparing flies subjected to different
      starvation regimes.

PMID- 16964496
TI  - How does the unicellular Tetrahymena utilise the hormones that it produces?
      Paying a visit to the realm of atto-and zeptomolar concentrations.
AB  - Changes in the hormone content of Tetrahymena pyriformis GL were investigated
      during histamine, serotonin or insulin treatment at concentrations of 10(-6)M to
      10(-21)M for 30 min. The immunologically demonstrable hormone content was studied
      by using specific antibodies, flow cytometry and confocal microscopy. Histamine
      at the higher ranges elevated the serotonin content of Tetrahymena, whereas
      serotonin at the lower ranges (down to 10(-21)M) decreased its histamine levels.
      Insulin did not affect its serotonin content, whereas serotonin increased its
      insulin content at each concentration studied (down to 10(-21)M). Insulin between
      10(-6)M and 10(-21)M increased the histamine levels of Tetrahymena, although
      histamine influenced its insulin level only at 10(-6)M. Our results call
      attention to the presence of hormonal interactions even at "low" levels of
      phylogeny and to the extreme sensitivity of the hormone receptors of Tetrahymena.
      These data might explain (1) the requirement of Tetrahymena for (vertebrate)
      hormone production and hormone receptors and (2) the way that it uses these
      hormones under natural conditions.

PMID- 16964497
TI  - Network metrics reveal differences in social organization between two fission
      fusion species, Grevy's zebra and onager.
AB  - For species in which group membership frequently changes, it has been a challenge
      to characterize variation in individual interactions and social structure.
      Quantifying this variation is necessary to test hypotheses about ecological
      determinants of social patterns and to make predictions about how group dynamics
      affect the development of cooperative relationships and transmission processes.
      Network models have recently become popular for analyzing individual contacts
      within a population context. We use network metrics to compare populations of
      Grevy's zebra (Equus grevyi) and onagers (Equus hemionus khur). These closely
      related equids, previously described as having the same social system, inhabit
      environments differing in the distribution of food, water, and predators. Grevy's
      zebra and onagers are one example of many sets of coarsely similar fission-fusion
      species and populations, observed elsewhere in other ungulates, primates, and
      cetaceans. Our analysis of the population association networks reveals contrasts
      consistent with their distinctive environments. Grevy's zebra individuals are
      more selective in their association choices. Grevy's zebra form stable cliques,
      while onager associations are more fluid. We find evidence that females associate
      assortatively by reproductive state in Grevy's zebra but not in onagers. The
      current approach demonstrates the utility of network metrics for identifying fine
      grained variation among individuals and populations in association patterns. From
      our analysis, we can make testable predictions about behavioral mechanisms
      underlying social structure and its effects on transmission processes.

PMID- 16964498
TI  - Population dynamics of thrips prey and their mite predators in a refuge.
AB  - Prey refuges are expected to affect population dynamics, but direct experimental
      tests of this hypothesis are scarce. Larvae of western flower thrips
      Frankliniella occidentalis use the web produced by spider mites as a refuge from
      predation by the predatory mite Neoseiulus cucumeris. Thrips incur a cost of
      using the refuge through reduced food quality within the web due to spider mite
      herbivory, resulting in a reduction of thrips developmental rate. These
      individual costs and benefits of refuge use were incorporated in a stage
      structured predator-prey model developed for this system. The model predicted
      higher thrips numbers in presence than in absence of the refuge during the
      initial phase. A greenhouse experiment was carried out to test this prediction:
      the dynamics of thrips and their predators was followed on plants damaged by
      spider mites, either with or without web. Thrips densities in presence of
      predators were higher on plants with web than on unwebbed plants after 3 weeks.
      Experimental data fitted model predictions, indicating that individual-level
      measurements of refuge costs and benefits can be extrapolated to the level of
      interacting populations. Model-derived calculations of thrips population growth
      rate enable the estimation of the minimum predator density at which thrips
      benefit from using the web as a refuge. The model also predicted a minor effect
      of the refuge on the prey density at equilibrium, indicating that the effect of
      refuges on population dynamics hinges on the temporal scale considered.

PMID- 16964499
TI  - Long-term response of Dreissena polymorpha larvae to physical and biological
      forcing in a shallow lake.
AB  - Muggelsee, a shallow eutrophic lake (Berlin, Germany), has been subject to global
      warming and concurrent reductions of anthropogenic nutrient loading during the
      past decades. Here, we focus on the recent increase in abundance of Dreissena
      polymorpha larvae. We aimed at ascertaining whether the change in abundance of
      larvae was driven by changes in climate, especially by climate warming, and/or by
      the concurrent changes in trophic state of the lake. Both the numbers of small,
      newly developed larvae and their lengths have increased in recent years,
      suggesting that conditions for overall reproductive success have improved. The
      timing of the increase in abundance of larvae was matched by changes in nutrient
      loading and phytoplankton biomass, induced by a reduced inflow of nutrients into
      the lake. Besides a correlation between the first appearance of larvae each year
      and the timing of the requisite temperature for first spawning (12 degrees C), no
      relationship between changes in water temperature and abundance, length and
      survival rates of larvae was found. However, a sudden drop in abundance of larvae
      in 2003 may be primarily attributed to low dissolved oxygen conditions during an
      unusually long period of stratification, induced by anomalous meteorological
      conditions. The increase in length and survival rates of larvae was most likely
      due to changes in food composition, which followed the decrease in nutrient
      availability, and to changes in the occurrence of planktivorous fish. The results
      suggest that the first appearance of larvae per year and the decline in abundance
      of larvae in 2003 were driven by climatic influences, while the overall increase
      in abundance and length of D. polymorpha larvae in Muggelsee was more likely
      caused by changes in the trophic state of the lake rather than by climate
      warming.

PMID- 16964500
TI  - Impact of local temperature increase on the early development of biofilm
      associated ciliate communities.
AB  - Indications of global climate change and associated unusual temperature
      fluctuations have become increasingly obvious over the past few decades.
      Consequently, the relevance of temperature increases for ecological communities
      and for whole ecosystems is one of the major challenges of current ecological
      research. One approach to investigating the effects of increasing temperatures on
      communities is the use of fast-growing microbial communities. Here we introduce a
      river bypass system in which we tested the effect of temperature increases (0, 2,
      4, 6 degrees C above the long-term average) on both the colonization speed and
      the carrying capacity of biofilm-associated ciliate communities under different
      seasonal scenarios. We further investigated interactions of temperature and
      resource availability by cross-manipulations in order to test the hypothesis that
      temperature-mediated effects will be strongest in environments that are not
      resource-limited. Strong seasonal differences in both tested parameters occurred
      under natural conditions (no resource addition), and the effects of temperature
      increase at a given time were relatively low. However, increasing temperature can
      significantly accelerate the colonization speed and reduce the carrying capacity
      in particular seasons. These effects were strongest in winter. Simultaneous
      manipulation of temperature and of resource availability amplified the response
      to temperature increase, adumbrating strong interactive control of populations by
      temperature and resource availability. Our results show that the response of
      communities to local temperature increases strongly depends on the seasonal
      setting, the resource availability and the stage of succession (early
      colonization speed vs. carrying capacity).

PMID- 16964501
TI  - Control of microbial communities by the macrofauna: a sensitive interaction in
      the context of extreme summer temperatures?
AB  - Climate models predict an increasing frequency of extremely hot summer events in
      the northern hemisphere for the near future. We hypothesised that microbial
      grazing by the metazoan macrofauna is an interaction that becomes unbalanced at
      high temperatures due to the different development of the grazing rates of the
      metazoans and the growth rates of the microbial community with increasing
      temperature. In order to test this hypothesis, we performed grazing experiments
      in which we measured the impact of increasing temperatures on the development of
      the grazing rates of riverine mussels in relation to the growth rates of a
      unicellular prey community (a natural heterotrophic flagellate community from a
      large river). In a first experimental series using Corbicula fluminea as a grazer
      and under the addition of a carbon source (yeast extract), the increase of the
      prey's growth rates was considerably stronger than that of the predator's grazing
      rates when temperatures were increased from 19 to over 25 degrees C. This was
      also the outcome when the mussels had been acclimatized to warm temperatures.
      Hereafter, specific experiments with natural river water at temperatures of 25
      and 30 degrees C were performed. Again, a strong decrease of the mussels' grazing
      rates in relation to the flagellate growth rates with increasing temperature
      occurred for two mussel species (C. fluminea and Dreissena polymorpha). When
      performing the same experiment using a benthic microbial predator community
      (biofilms dominated by ciliates) instead of the benthic mussels, an increase of
      the grazing rates relative to the growth rates with temperature could be
      observed. Our data suggest that predator-prey interactions (between metazoans and
      microbes) that are balanced at moderate temperatures could become unbalanced at
      high temperatures. This could have significant effects on the structure and
      function of microbial communities in light of the predicted increasing frequency
      of summer heat waves.

PMID- 16964502
TI  - Effects of climate-driven temperature changes on the diversity of freshwater
      macroinvertebrates.
AB  - Increasing temperatures due to climate change were found to influence abundance
      and timing of species in numerous ways. Whereas many studies have investigated
      climate-induced effects on the phenology and abundance of single species, less is
      known about climate-driven shifts in the diversity and composition of entire
      communities. Analyses of long-term data sets provide the potential to reveal such
      relationships. We analysed time series of entire communities of macrozoobenthos
      in lakes and streams in Northern Europe. There were no direct linear effects of
      temperature and climate indices (North Atlantic Oscillation index) on species
      composition and diversity, but using multivariate statistics we were able to show
      that trends in average temperature have already had profound impacts on species
      composition in lakes. These significant temperature signals on species
      composition were evident even though we analysed comparatively short time periods
      of 10-15 years. Future climate shifts may thus induce strong variance in
      community composition.

PMID- 16964503
TI  - Spring bloom succession, grazing impact and herbivore selectivity of ciliate
      communities in response to winter warming.
AB  - This study aimed at simulating different degrees of winter warming and at
      assessing its potential effects on ciliate succession and grazing-related
      patterns. By using indoor mesocosms filled with unfiltered water from Kiel Bight,
      natural light and four different temperature regimes, phytoplankton spring blooms
      were induced and the thermal responses of ciliates were quantified. Two distinct
      ciliate assemblages, a pre-spring and a spring bloom assemblage, could be
      detected, while their formation was strongly temperature-dependent. Both
      assemblages were dominated by Strobilidiids; the pre-spring bloom phase was
      dominated by the small Strobilidiids Lohmaniella oviformis, and the spring bloom
      was mainly dominated by large Strobilidiids of the genus Strobilidium. The
      numerical response of ciliates to increasing food concentrations showed a strong
      acceleration by temperature. Grazing rates of ciliates and copepods were low
      during the pre-spring bloom period and high during the bloom ranging from 0.06
      (Delta0 degrees C) to 0.23 day(-1) (Delta4 degrees C) for ciliates and 0.09
      (Delta0 degrees C) to 1.62 day(-1) (Delta4 degrees C) for copepods. During the
      spring bloom ciliates and copepods showed a strong dietary overlap characterized
      by a wide food spectrum consisting mainly of Chrysochromulina sp., diatom chains
      and large, single-celled diatoms.

PMID- 16964504
TI  - Proton thrusters: overview of the structural and functional features of soluble
      tetrahaem cytochromes c3.
AB  - Tetrahaem cytochromes c (3) from sulfate-reducing bacteria have revealed
      exquisite complexity in their ligand binding properties and they couple the
      cooperative binding of two electrons with the binding of protons. In this review,
      the molecular mechanisms for these cooperative effects are described, and the
      functional consequences of these cooperativities are discussed in the context of
      the general mechanisms of biological energy transduction and the specific
      physiological metabolism of Desulfovibrio.

PMID- 16964505
TI  - Catecholase activity of dicopper(II)-bispidine complexes: stabilities and
      structures of intermediates, kinetics and reaction mechanism.
AB  - A mechanism for the oxidation of 3,5-di-tert-butylcatechol (dtbc) with dioxygen
      to the corresponding quinone (dtbq), catalyzed by bispidine-dicopper complexes
      (bispidines are various mono- and dinucleating derivatives of 3,7
      diazabicyclo[3.3.1]nonane with bis-tertiary-amine-bispyridyl or bis-tertiary
      amine-trispyridyl donor sets), is proposed on the basis of (1) the stoichiometry
      of the reaction as well as the stabilities and structures [X-ray, density
      functional theory (B3LYP, TZV)] of the bispidine-dicopper(II)-3,4,5,6
      tetrachlorcatechol intermediates, (2) formation kinetics and structures
      (molecular mechanics, MOMEC) of the end-on peroxo-dicopper(II) complexes and (3)
      kinetics of the stoichiometric (anaerobic) and catalytic (aerobic) copper-complex
      assisted oxidation of dtbc. This involves (1) the oxidation of the dicopper(I)
      complexes with dioxygen to the corresponding end-on peroxo-dicopper(II)
      complexes, (2) coordination of dtbc as a bridging ligand upon liberation of
      H(2)O(2) and (3) intramolecular electron transfer to produce dtbq, which is
      liberated, and the dicopper(I) catalyst. Although the bispidine complexes have
      reactivities comparable to those of recently published catalysts with macrocyclic
      ligands, which seem to reproduce the enzyme-catalyzed process in various reaction
      sequences, a strikingly different oxidation mechanism is derived from the
      bispidine-dicopper-catalyzed reaction.

PMID- 16964506
TI  - An examination of the binding behavior of histidine-containing peptides with
      immobilized metal complexes derived from the macrocyclic ligand, 1,4,7
      triazacyclononane.
AB  - In this study, two different experimental approaches have been employed to
      examine the binding behavior of histidine-containing peptides with metal ion
      complexes derived from the macrocyclic ligand 1,4,7-triazacyclononane (tacn).
      Firstly, a molecular modeling approach has been employed to derive the strain
      energies for test peptide sequences that have a predicted propensity to readily
      adopt an alpha-helical conformation. To this end, binuclear metal complexes were
      examined with peptides containing two histidine residues in different locations
      in a pair of peptides of the same composition but different sequence. These
      modeling results indicate that there are no energetic constraints for two-point
      binding to occur with dicopper(II) binuclear complexes when two histidine
      residues are appropriately placed in an alpha-helical conformation. Secondly,
      binding experiments were carried out to establish the effect of one or more
      histidine residues within a peptide sequence on the affinity of a peptide for
      these Cu(II)-tacn derived binuclear complexes when immobilized onto a
      chromatographic support material. The results confirm that for all chelating
      systems, higher affinity is achieved as the histidine number in the peptide
      structure increases, although the relative location of the histidine residues in
      these small peptides did not introduce a significant constraint to the
      conformation on interacting with the immobilized Cu(II) binuclear complexes.

PMID- 16964507
TI  - Comment on "Transpedicle body augmenter in painful osteoporotic compression
      fractures" (Kung-Chia Li, Anna F.-Y. Li, Ching-Hsiang Hsieh, Hsiang-Ho Chen).

PMID- 16964508
TI  - Caenorhabditis elegans in the study of SMN-interacting proteins: a role for SMI
      1, an orthologue of human Gemin2 and the identification of novel components of
      the SMN complex.
AB  - Spinal muscular atrophy is a common neuromuscular disorder caused by mutations in
      the survival motor neuron (SMN) gene. In mammals, SMN is tightly associated with
      Gemin2. To gain further insight into the functions of SMN and Gemin2, we have
      cloned and sequenced smi-1 (Survival of Motor neuron-Interacting protein 1), a C.
      elegans homologue of the human Gemin2 gene. We show that the SMI-1 expression
      pattern and RNA interference phenotype show considerable overlap with that
      previously reported for SMN-1. Finally, we demonstrate that the SMN-1 and SMI-1
      proteins directly interact. Having demonstrated the utility of the C. elegans
      genetic model for investigating genes encoding SMN-interacting proteins, we have
      undertaken a yeast two-hybrid screen of a C. elegans cDNA library to identify
      novel proteins that interact with SMN-1. We show the direct interaction of SMN-1
      with nine novel proteins, several of which may be involved in RNA metabolism.

PMID- 16964509
TI  - Proteomic based investigation of rhamnolipid production by Pseudomonas
      chlororaphis strain NRRL B-30761.
AB  - We recently reported that a strain of the non-pathogenic bacterial species
      Pseudomonas chlororaphis was capable of producing the biosurfactant molecule,
      rhamnolipids. Previous to this report the organisms known to produce rhamnolipids
      were almost exclusively pathogens. The newly described P. chlororaphis strain
      produced rhamnolipids at room temperature in static minimal media, as opposed to
      previous reports of rhamnolipid production which occurred at elevated
      temperatures with mechanical agitation. The non-pathogenic nature and energy
      conserving production conditions make the P. chlororaphis strain an attractive
      candidate for commercial rhamnolipid production. However, little characterization
      of molecular/biochemical processes in P. chlororaphis have been reported. In
      order to achieve a greater understanding of the process by which P. chlororaphis
      produces rhamnolipids, a survey of proteins differentially expressed during
      rhamnolipid production was performed. Separation and measurement of the
      bacteria's proteome was achieved using Beckman Coulter's Proteome Lab PF2D packed
      column-based protein fractionation system. Statistical analysis of the data
      identified differentially expressed proteins and known orthologues of those
      proteins were identified using an AB 4700 Proteomics Analyzer mass spectrometer
      system. A list of proteins differentially expressed by P. chlororaphis strain
      NRRL B-30761 during rhamnolipid production was generated, and confirmed through a
      repetition of the entire separation process.

PMID- 16964510
TI  - Prospective controlled study of the diagnostic value of skin biopsy in patients
      with presumed meningococcal disease.
AB  - Microbiological tests for diagnosis of acute meningococcal disease are important
      for the clinical management of patients with this often-fatal illness, but
      cultures are frequently negative after antibiotics have been administered.
      Retrospective studies suggest that examination of skin biopsies may aid a rapid
      diagnosis and that cultures of skin biopsies are often positive even after
      antimicrobial treatment has commenced. This prospective controlled study aimed to
      assess the diagnostic value of skin biopsy compared with investigations of blood
      and cerebrospinal fluid (CSF) in patients with skin lesions and presumed
      meningococcal disease. A total of 43 patients, 31 with suspected acute
      meningococcal infection and 12 controls, were included. All skin biopsies were
      investigated by Gram stain and routine microbiological culture. In 25 patients,
      meningococcal infection was diagnosed microbiologically. The clinical diagnosis
      was meningococcal meningitis in 8 patients, meningococcal sepsis in 11 patients,
      and a combination of both in 6 patients. The sensitivity of cultures of blood,
      CSF, and skin biopsies was 56%, 50%, and 36%, respectively. When culture and Gram
      stain were combined, positive results were obtained in 56%, 64%, and 56%,
      respectively. There was no correlation between the diagnostic yield of skin
      biopsies and previous antibiotic treatment. In 14 patients, the diagnosis was
      based exclusively on one positive sample: CSF in 7 (28%) patients, blood in 4
      (16%) patients, and skin biopsy in 3 (12%) patients. The sensitivity of skin
      biopsies was highest in patients with the least extensive skin lesions.
      Specificity was 100%. Microbiological investigation of skin biopsies increased
      the diagnostic yield and could be considered a component of the routine
      diagnostic work-up in patients with suspected meningococcal infection, even after
      the initiation of antimicrobial treatment.

PMID- 16964511
TI  - Silica-guanidinium thiocyanate-based nucleic acid isolation protocol does not
      improve sensitivity of two commercial tests for detection of Mycobacterium
      tuberculosis in respiratory samples.

PMID- 16964512
TI  - Negatively correlated firing: the functional meaning of lateral inhibition within
      cortical columns.
AB  - Lateral inhibition is a well documented aspect of neural architecture in the main
      sensory systems. Existing accounts of lateral inhibition focus on its role in
      sharpening distinctions between inputs that are closely related. However, these
      accounts fail to explain the functional role of inhibition in cortical columns,
      such as those in V1, where neurons have similar response properties. In this
      paper, we outline a model of position tracking using cortical columns of
      integrate-and-fire and Hodgkin-Huxley-type neurons which respond optimally to a
      particular location, to show that negatively correlated firing patterns arise
      from lateral inhibition in cortical columns and that this provides a clear
      benefit for population coding in terms of stability, accuracy, estimation time
      and neural resources.

PMID- 16964513
TI  - Anthropometry of the medial tibial condyle to design the tibial component for
      unicondylar knee arthroplasty for the Korean population.
AB  - Unicondylar knee arthroplasty (UKA) has gained popularity in the recent years for
      treating medial compartment osteoarthritis of the knee joint in the Asian
      population. There is little information about the anthropometry of the resected
      bony surfaces of the knee joint in these population groups for designing the
      appropriate size-matched UKA components. We studied the anthropometry of the
      resected medial tibial condyles in 50 male and 50 female Korean cadavers by using
      three-dimensional computer tomography. We measured the anteroposterior dimension,
      the mediolateral dimension at defined points and the condylar aspect ratio. These
      measurements were compared with similar dimensions of the tibial components from
      five conventionally used UKA designs. Statistical analysis was performed using
      Student's t-test, Paired t-test and Pearson's correlation coefficient. We found
      that three of the tibial component designs showed mediolateral overhang for the
      whole range of measured anteroposterior dimensions of the resected medial tibial
      condyles, whereas one of the designs (DePuy) showed mediolateral undersizing for
      the smaller AP dimensions and overhang for the larger AP dimensions of the
      resected medial tibial condyles. Another design (Smith and Nephew) showed
      mediolateral undersizing for the whole range of measured anteroposterior
      dimensions of the resected medial tibial condyle. We found a decrease in the
      condylar aspect ratio with increasing AP dimension for our cadaver population
      data. However, the majority of the conventional tibial prosthesis showed either a
      constant condylar aspect ratio or an increasing aspect ratio (DePuy) with the
      increasing AP dimension of the resected medial tibial condyle. Our study may
      provide guidelines for designing appropriate tibial UKA components for a majority
      of Asian sub-populations and encourage similar studies in other population
      groups.

PMID- 16964514
TI  - Biocompatibility of a polymer patch for rotator cuff repair.
AB  - Both mechanical and biological factors influence the high re-tear rate after
      rotator cuff repair. Mechanical factors have largely been addressed by the
      introduction of better implants and modification of suture configuration, but
      further improvements are needed to address the often poor tissue quality of the
      degenerated rotator cuff tendons. Current biological solutions provide only short
      term reinforcement and have been associated with pseudo-infectious reactions.
      This pre-clinical animal study investigates the biological response to a novel
      polycarbonate polyurethane patch used for tissue augmentation in a rat rotator
      cuff repair model. Bilateral defects were created in the supraspinatus tendons of
      12 Sprague Dawley rats. One side was repaired with a patch as a tissue
      augmentation device. The contralateral side acted as internal control without
      patch augmentation. After 6 weeks the tissues were harvested and underwent
      histologic and histomorphometric analyses. Histological evaluation demonstrated
      no inflammatory reaction; histomorphometry revealed tissue ingrowth of 79.9%. In
      conclusion, the polycarbonate polyurethane patch for tissue extension or
      augmentation in rotator cuff repair has demonstrated no inflammatory response and
      excellent tissue integration in a rat rotator cuff repair model.

PMID- 16964515
TI  - Multiple osteochondroses of bilateral knee joints: a case report.
AB  - Knee injuries in young athletes include not only the typical adult bone injuries,
      ligament and cartilage, but also the growth plate lesions. Osteochondroses are
      idiopathic, self-limited disturbance of enchondral ossification in which a rapid
      growth spurt is present. The patella could be affected by two different kinds of
      osteochondroses: Kohler syndrome and Sinding-Larsen-Johansson. Here we are
      reporting the first case of simultaneous location of osteochondroses of the two
      ossification centers of both patella. A 9-year-old boy, competitive skater,
      presented a history of anterior knee pain involving both knees. Standard X-rays,
      axial patellar view, MRI and arthro-MR were performed. In order to follow the
      natural history of the pathology and the evolution of the healing, examinations
      at 2 years were repeated. We proposed the young skater a medical and a
      physiotherapeutic treatment based on unloading, isometric exercises, NSAID. As
      the symptoms improve a gradual return to competitive sports activity was allowed.
      The case mentioned above can be considered an atypical case because the patient
      suffered for a bilateral knee osteochondroses, involving simultaneously the
      primary ossification centre (Kohler syndrome) and the secondary ossification
      centre (Larsen syndrome) of the patella.

PMID- 16964516
TI  - A prospective comparison of bone-patellar tendon-bone and hamstring tendon grafts
      for anterior cruciate ligament reconstruction in male patients.
AB  - The aim of the study was to compare the results after arthroscopic anterior
      cruciate ligament (ACL) reconstruction using central-third, bone-patellar tendon
      bone (BPTB Group) (n = 45) and four-strand semitendinosus/gracilis (ST/G Group)
      (n = 78) autografts in male patients. The type of study is non-randomised,
      prospective consecutive series. A consecutive series of 126 male patients, all
      with unilateral ACL ruptures, was included in the study. In both groups,
      interference screw fixation of the graft was used at both ends and 123/126 (97%)
      of the patients returned for the follow-up examination after a period of 25 (23
      33) months. The pre-operative assessments in both groups were similar in terms of
      the Tegner activity level, the Lysholm knee scoring scale, KT-1000 measurements,
      one-leg-hop test and knee-walking test. A significant reduction in knee laxity as
      measured with the KT-1000 arthrometer, compared with the pre-operative
      assessments, was found in both groups (P < 0.001). No significant differences in
      the post-operative knee-laxity measurements were found between the groups. Both
      groups had a significantly improved functional outcome at follow-up in terms of
      the Lysholm knee scoring scale, Tegner activity level and one-leg-hop test. The
      BPTB Group had a significantly higher Tegner activity level at follow-up,
      compared with the ST/G Group (P = 0.02). Moreover, the patients in the BPTB Group
      were significantly more likely to have a Tegner activity level of 6 or above (P =
      0.03). Otherwise, no significant differences were found between the two study
      groups at the 2-year follow-up. Two years after an ACL reconstruction, the two
      groups displayed no significant differences in terms of functional outcome and
      knee laxity. However, more patients in the BPTB Group returned to a higher Tegner
      activity level than that in the ST/G Group.

PMID- 16964517
TI  - Bioabsorbable screw divergence angle, not tunnel preparation method influences
      soft tissue tendon graft-bone tunnel fixation in healthy bone.
AB  - Bone tunnel fixation of a soft tissue tendon graft is the weak link immediately
      following ACL reconstruction. This biomechanical study evaluated the influence of
      extraction drilled or step dilated bone tunnels and bioabsorbable screw
      divergence on soft tissue tendon graft fixation. From an initial group of 50
      available specimens, similar apparent bone mineral density porcine tibiae (1.2 +/
      0.24 g/cm2) were divided into two groups of ten specimens each. Group 1
      (extraction drilled) received 9 mm diameter tunnels. Group 2 (step dilated)
      received 7 mm diameter tunnels that were dilated to 9 mm. Grafts were secured in
      tunnels using 10 mm diameter, 35 mm long tapered screws. After high resolution CT
      scanning to evaluate screw divergence, constructs were pretensioned on a servo
      hydraulic device between 10 and 50 N for 10 cycles, and isometric pretensioned at
      50 N for 1 min, prior to 500 sub-maximal loading cycles (50-200 N) and load to
      failure testing at 20 mm/min. Wilcoxon Signed Rank tests and Mann-Whitney U-tests
      were used to evaluate group differences. Coefficient of determination values (r2)
      were calculated to further delineate statistically significant relationships.
      Tunnel preparation method did not display statistically significant effects on
      insertion torque, displacement during cyclic testing, relative stiffness during
      cyclic testing, load at failure, stiffness during load to failure testing or
      displacement during load to failure testing. Screw divergence < 15 degrees
      produced lower displacement and greater relative stiffness during cyclic testing
      and greater load at failure and stiffness during load to failure testing. Screw
      divergence angle displayed moderate relationships with construct displacement
      during cyclic testing (r2 = 0.54), stiffness during load to failure testing (r2 =
      0.60), and load at failure (r2 = 0.41). Tunnel dilation does not enhance soft
      tissue tendon graft fixation strength in healthy bone. Bioabsorbable screw
      divergence of > or = 15 degrees significantly reduces soft tissue tendon graft
      bone tunnel fixation.

PMID- 16964518
TI  - Analysis of the success and failure of endoscopic third ventriculostomy in
      infants less than 1 year of age.
AB  - OBJECTIVES: In infants less than 1 year of age, the value of endoscopic third
      ventriculostomy (ETV) is controversial. It is believed to cause more morbidity
      and to have higher failure rates. We analyzed our data enlarging the reported
      pool of ETV outcome in infants less than 1 year of age. MATERIALS AND METHODS: We
      performed 12 ETVs in ten patients younger than 1 year of age. All patients had
      predominant supratentorial hydrocephalus. We defined ETV success as a shunt-free
      follow-up of at least 12 months, however, allowing re-ETV. CONCLUSION: ETV should
      be considered as initial treatment and carries low morbidity in these infants. As
      the immune system rapidly matures, postponing shunt implantation for several
      months or even weeks would make an ETV procedure worthwhile. On the other hand,
      as success probability rapidly increases 4 months after birth, re-ETV should
      always be considered first.

PMID- 16964519
TI  - Total body water measurement by a modification of the bioimpedance spectroscopy
      method.
AB  - We propose a method for calculating directly total body water (TBW) volumes (V
      (t)) from whole body resistance extrapolated at infinite frequency (R (infinity))
      using a XITRON 4200 impedance meter. Mean TBW resistivities for men and women
      were determined from measurements of R (infinity) and fat-free mass (FFM(d))
      measured by DXA in 58 healthy subjects assuming an average hydration coefficient
      of 73.2%. Mean differences between V (t) measured by our new method and those
      deduced from DXA data were +0.11 +/- 1.61 L for women and +0.13 +/- 2.16 L for
      men. For validation, this method was tested with the same resistivities against a
      2nd group of 16 volunteers and the mean difference between V (t) from impedance
      and DXA was -0.80 +/- 1.43 L. Since the resistance at 50 kHz (R (50)) was found
      to be equal, in average, to 1.230 R (infinity) for men and 1.223 R (infinity) for
      women, this method can also be applied at 50 kHz with a similar accuracy by
      estimating R (infinity) from R (50). When our new method was applied to the
      monitoring of water loss during 28 dialysis runs performed on 13 patients, it
      predicted a mean water loss equal to 94% of ultrafiltered volume.

PMID- 16964520
TI  - Betulinic acid decreases expression of bcl-2 and cyclin D1, inhibits
      proliferation, migration and induces apoptosis in cancer cells.
AB  - Betulinic acid (BA) is a pentacyclic triterpene found in many plant species,
      among others in the bark of white birch Betula alba. BA was reported to display a
      wide range of biological effects, including antiviral, antiparasitic,
      antibacterial and anti-inflammatory activities, and in particular to inhibit
      growth of cancer cells. The aim of the study was further in vitro
      characterization of BA anticancer activity. In this study, we demonstrated a
      remarkable antiproliferative effect of BA in all tested tumor cell cultures
      including neuroblastoma, rabdomyosarcoma-medulloblastoma, glioma, thyroid,
      breast, lung and colon carcinoma, leukemia and multiple myeloma, as well as in
      primary cultures isolated from ovarian carcinoma, cervical carcinoma and
      glioblastoma multiforme. Furthermore, we have shown that BA decreased cancer cell
      motility and induced apoptotic cell death. We also observed decrease of bcl2 and
      cyclin D1 genes expression, and increase of bax gene expression after betulinic
      acid treatment. These findings demonstrate the anticancer potential of betulinic
      acid and suggest that it may be taken into account as a supportive agent in the
      treatment of cancers with different tissue origin.

PMID- 16964521
TI  - Microsatellites, single nucleotide polymorphisms and a sequence tagged site in
      starch-synthesizing genes in relation to starch physicochemical properties in
      nonwaxy rice (Oryza sativa L.).
AB  - Starch characteristics determine the quality of various products of rice, e.g.,
      eating, cooking and processing qualities. Our previous study indicated that
      molecular markers inside or close to starch synthesizing genes can differentiate
      the starch properties of 56 waxy rices. Here we report microsatellite (or simple
      sequence repeat, SSR) polymorphism in the Waxy (Wx) gene, soluble starch synthase
      I gene (SS1) and starch branching enzyme 1 gene (SBE1), single nucleotide
      polymorphism (SNP) in Wx and starch branching enzyme 3 gene (SBE3), and a
      sequence tagged site (STS) in starch branching enzyme 1 gene (SBE1) among 499
      nonwaxy rice samples and their relationships with starch physicochemical
      properties. The nonwaxy rice samples consist of landraces (n = 172) obtained from
      germplasm centers and cultivars and breeding lines (n = 327) obtained from
      various breeding programs. Ten (CT)( n ) microsatellite alleles, (CT)(8),
      (CT)(10), (CT)(11), (CT)(12, )(CT)(17), (CT)(18), (CT)(19), (CT)(20), (CT)(21),
      and (CT)(22), were found at the Wx locus, of which (CT)(11) was the most
      frequent, and (CT)(12), (CT)(21) and (CT)(22) were identified for the first time.
      Four (CT)( n ) microsatellite alleles were found at the SBE1 locus, (CT)(8),
      (CT)(9), and (CT)(10 )together with an insertion sequence of CTCTCGGGCGA, and
      (CT)(8) alone without the insertion, of which (CT)(9) and the insertion was a new
      allele identified in only one rice, IR1552. Multiple microsatellites clustered at
      the SS1 locus, and in addition to the three alleles previously detected (SSS-A =
      (AC)(2)...TCC(TC)(11)...(TC)(5)C(ACC)(11), SSS-B =
      (AC)(3)...TCT(TC)(6)...(TC)(4)C(ACC)(9), and SSS-C =
      (AC)(3)...TCT(TC)(6)...(TC)(4)C(ACC)(8)), one new allele (SSS-D =
      (AC)(2)...TCC(TC)(10)...(TC)(4)C(ACC)(9)) was found. Analysis of the starch
      physicochemical properties of the samples with different microsatellites, SNPs
      and STS groups indicated that these molecular markers can differentiate almost
      all the physicochemical properties examined, e.g., apparent amylose content
      (AAC), pasting viscosity characteristics, and gel textural properties. Wx SSR and
      Wx SNP alone explained more variations for all physicochemical properties than
      the other molecular markers. The total six markers could explain 92.2, 81 and 86%
      of total variation of AAC, gel hardness (HD), and gel cohesiveness (COH),
      respectively, and they could explain more than 40% of the total variation of hot
      paste viscosity (HPV), cool paste viscosity (CPV), breakdown viscosity (BD),
      setback viscosity (SB) and gel adhesiveness (ADH). However, only 29% of the total
      variation of peak viscosity (PV) and 37% of pasting temperature (PT) could be
      explained by all the molecular markers. Some of these markers can differentiate
      the starch physicochemical properties among the rice samples with the same Wx
      allele, indicating that the variation within Wx allele classes can be explained
      by other starch synthesizing genes. These SSRs, SNPs and STS are useful in marker
      assisted breeding for the improvement of starch quality of rice.

PMID- 16964524
TI  - Thymic output, ageing and zinc.
AB  - The role of the thymus is vital for orchestration of T-cell development and
      maturation. With increasing age the thymus undergoes a process of involution
      which results in a reduction in thymic size, function and output. Until
      relatively recent it was not feasible to accurately measure the magnitude of age
      related loss of thymic function. With the discovery of T-cell receptor excision
      circles (TRECs), which are the stable by-products of the newly generated T-cells,
      it is now possible to quantitatively measure the extent of thymic output. This
      review examines the available data on immune function and zinc deficiency and
      places them in the context of the aims of the ZINCAGE project which include the
      evaluation of the role played by zinc in maintaining thymic output in healthy
      elderly individuals.

PMID- 16964525
TI  - NF-kappaB, AP-1, Zinc-deficiency and aging.
AB  - Zinc (Zn) deficiency, a frequent condition in human population especially in aged
      persons, induces oxidative stress and subsequently activates/inhibits oxidant
      sensitive transcription factors that can affect cell function, proliferation and
      survival leading to disease. Zn deficiency-triggered oxidative stress could
      affect cell signalling, including transcription factors containing Zn finger
      motifs and other oxidant-sensitive transcription factors such as nuclear factor
      kappa B (NF-kappaB) and activator protein-1 (AP-1). AP-1 can be activated in Zn
      deficiency that can occur secondary to an increase in cellular H(2)O(2), followed
      by activation of MAPKs p38 and JNK. Similarly, the cytosolic steps of the NF
      kappaB cascade are activated by oxidants in Zn deficiency. However, an impaired
      nuclear transport of the active transcription factor leads to a low expression of
      NF-kappaB-dependent genes that could be involved in multiple steps of Zn
      deficiency associated pathology. We present here evidence that, following
      experimental depletion of Zn, both NF-kappaB and AP-1 signallings are altered in
      primary T cells isolated from young and elderly healthy individuals under
      CD3/CD28 costimulation. A supplementation of Zn restored both NF-kappaB and AP-1
      activation in CD3/CD28 costimulated T cells from young, but not from elderly,
      healthy individuals, indicating that the Zn deficiency is only one component of a
      more complex mechanism involved in immunosenescence. In this review we summarize
      our present knowledge on NF-kappaB and AP-1 activation and underline the role of
      Zn in this process, especially in the context of Zn deficiency observed in aged
      persons leading to immunosenescence.

PMID- 16964522
TI  - The influence of cardiovascular and antiinflammatory drugs on thiazide-induced
      hemodynamic and saluretic effects.
AB  - OBJECTIVE: Thiazide diuretics are known to induce a transient fall of the
      glomerular filtration rate (GFR), which, in turn, reduces tubular Na(+) load.
      This tubuloglomerular feedback (TGF) curtails the natriuretic effect of this
      class of diuretics. Cardiovascular and antiinflammatory therapeutics may
      interfere with TGF and thereby influence the effect of thiazides once co
      administration is clinically indicated. METHODS: The effects on GFR and saluresis
      of hydrochlorothiazide (HCT; 25 mg) monotherapy were measured in healthy
      volunteers and compared to those obtained during co-administration of the
      thiazide and a second therapeutic. RESULTS: In the presence of the ACE inhibitor
      enalapril (10 mg), the transient fall in the GFR induced by HCT was almost
      abolished, and Na(+) excretion increased by approximately 30 % as compared to HCT
      monotherapy. K(+) excretion, however, remained unchanged. Similar results were
      obtained with the AT II type 1 receptor antagonist candesartan (8 mg): GFR
      remained stable, Na(+) excretion rose by 35 % and K(+) excretion was not changed.
      The effect of the Ca(2+) channel blocker amlodipine (5 mg) on GFR and HCT-induced
      Na(+) excretion equalled that obtained with the AT(1) blocker, yet with this
      treatment K(+) excretion rose in proportion to Na(+) excretion. The beta-blockers
      propranolol (80 mg) or bisoprolol (5 mg) reduced GFR but maintained TGF. HCT
      induced Na(+) excretion was significantly reduced in the presence of a beta
      blocker, whereas K(+) excretion was not changed. The inhibition of cyclooxygenase
      by diclofenac (50 mg) or rofecoxib (25 mg) significantly reduced the
      diuretic/natriuretic effect of HCT, but K(+) excretion was unchanged, and TGF was
      still demonstrable. CONCLUSION: In conclusion, AT(1) receptors, as well as the
      Ca(2+) channels in the smooth muscle cells of the afferent arteriole, are
      considered prerequisites for TGF function; their blockade increases the
      diuretic/natriuretic efficacy of thiazide diuretics. In contrast, beta-blockers
      and COX inhibitors do not interfere directly with TGF. These first dose effects
      reflect the primary response of the kidney to the drugs. They cannot, however,
      predict the benefits of long-term treatment.

PMID- 16964526
TI  - Protein homeostasis and molecular chaperones in aging.
AB  - Molecular chaperones are ubiquitous, highly conserved proteins responsible for
      the maintenance of protein folding homeostasis in cells. Environmental stress
      causes proteotoxic damage, which triggers chaperone induction and the subsequent
      reparation of cellular damage by chaperones, including disposing irreparable
      protein ensembles. We summarize the current view of protein damage, turnover, the
      stress response and chaperone function in aging, and review novel data showing
      that accumulation of misfolded proteins outcompete and overload the limited
      resources of the protein folding, maintenance and turnover system, compromising
      general protein homeastasis and cellular function. Possible involvement of
      chaperones and proteolysis in immunosenescence is highlighted. Defects in zinc
      metabolism are also addressed in relation to aging and changes in chaperone
      levels.

PMID- 16964527
TI  - Acidosis enhances toxicity induced by kainate and zinc exposure in aged cultured
      astrocytes.
AB  - A key feature of cerebral ischemia, one of the leading causes of death associated
      with ageing, is excessive accumulation of glutamate in the synaptic cleft. In
      some forms of cerebral ischemia, like transient global ischemia, high levels or
      synaptic glutamate are complemented by a concomitant increase in extracellular
      Zn(2+) as result of the release of the cation that is present in the pre-synaptic
      vesicles of glutamatergic neurons. Interestingly, while neurons are very
      sensitive to the toxicity triggered by exposure to either glutamate or Zn(2+),
      astrocytes show less vulnerability to these toxins. We examined the vulnerability
      of cortical type 1 astrocytes to a combined exposure to the AMPA/kainate receptor
      agonist kainate and Zn(2+). Astrocytes exposed to 1 mM kainate for 1 h did not
      exhibit any degeneration in the following 24 h, and addition of 50 microM Zn(2+)
      to the kainate exposure failed to produce any further glial loss. Another
      hallmark of cerebral ischemia is parechymal acidosis and therefore, we tested the
      susceptibility of our cultured astrocytes to a kainate/Zn(2+) exposure performed
      under acidotic conditions. We found that the combination of 1 h exposure to 1 mM
      kainate + 50 microM Zn(2+) at pH 6.2 produced a strong increase in intracellular
      free Zn(2+) ([Zn(2+)](i)), and extensive glial injury. Comparing [Zn(2+)](i)
      rises triggered by kainate/Zn(2+) exposure at pH 7.4 or pH 6.2 we found that
      acidosis promotes increased toxic [Zn(2+)](i) levels as a result of a lethal
      combination of both enhanced Zn(2+) influx through Zn(2+) permeable AMPA/kainate
      channels and impaired intracellular buffering of the cation.

PMID- 16964528
TI  - Angiogenesis treatment, new concepts on the horizon.

PMID- 16964529
TI  - Community analysis in stream biomonitoring: what we measure and what we don't.
AB  - Diatom assemblages from 83 epilithic samples taken from the Mesta River,
      Bulgaria, were regressed against three sets of predictor variables, i.e.
      environmental, spatial, and temporal. Redundancy analysis (RDA) of species and
      environmental data explained 36% of the diatom variance and extracted several
      important gradients of species distribution, associated with a downstream
      increase in nutrient levels, pH, temperature, and organic pollution. The
      inclusion of spatial and temporal variables in the RDA model captured additional
      24% of the diatom variance and revealed three more gradients, a spatial gradient
      represented by higher order polynomial terms of latitude and longitude, and two
      temporal gradients of annual and seasonal variation. Partial RDAs demonstrated
      that the unique contribution of each predictor set to the explained diatom
      variance was the highest in the spatial dataset (16%), followed by the
      environmental (9%), and the temporal (7%) datasets. The remaining 28% of the
      variance was explained by the covariance of the predictor sets. This suggests
      that in biomonitoring of single stream basins, the cheap and simple account of
      space and time would explain most of the variance in assemblage composition
      obviating the necessity of expensive and time-consuming environmental
      assessments. The nature of the underlying environmental mechanisms can be easily
      inferred from the diatom composition itself.

PMID- 16964531
TI  - Processing of ND NMR spectra sampled in polar coordinates: a simple Fourier
      transform instead of a reconstruction.
AB  - In order to reduce the acquisition time of multidimensional NMR spectra of
      biological macromolecules, projected spectra (or in other words, spectra sampled
      in polar coordinates) can be used. Their standard processing involves a regular
      FFT of the projections followed by a reconstruction, i.e. a non-linear process.
      In this communication, we show that a 2D discrete Fourier transform can be
      implemented in polar coordinates to obtain directly a frequency domain spectrum.
      Aliasing due to local violations of the Nyquist sampling theorem gives rise to
      base line ridges but the peak line-shapes are not distorted as in most
      reconstruction methods. The sampling scheme is not linear and the data points in
      the time domain should thus be weighted accordingly in the polar FT; however,
      artifacts can be reduced by additional data weighting of the undersampled
      regions. This processing does not require any parameter tuning and is
      straightforward to use. The algorithm written for polar sampling can be adapted
      to any sampling scheme and will permit to investigate better compromises in terms
      of experimental time and lack of artifacts.

PMID- 16964532
TI  - NMR assignment of human RGS18.

PMID- 16964530
TI  - Magic-angle spinning solid-state NMR of a 144 kDa membrane protein complex: E.
      coli cytochrome bo3 oxidase.
AB  - Recent progress in magic-angle spinning (MAS) solid-state NMR (SSNMR) has enabled
      multidimensional studies of large, macroscopically unoriented membrane proteins
      with associated lipids, without the requirement of solubility that limits other
      structural techniques. Here we present initial sample preparation and SSNMR
      studies of a 144 kDa integral membrane protein, E. coli cytochrome bo(3) oxidase.
      The optimized protocol for expression and purification yields approximately 5 mg
      of the enzymatically active, uniformly (13)C,(15)N-enriched membrane protein
      complex from each liter of growth medium. The preparation retains endogenous
      lipids and yields spectra of high sensitivity and resolution, consistent with a
      folded, homogenous protein. Line widths of isolated signals are less than 0.5
      ppm, with a large number of individual resonances resolved in the 2D and 3D
      spectra. The (13)C chemical shifts, assigned by amino acid type, are consistent
      with the secondary structure previously observed by diffraction methods. Although
      the structure is predominantly helical, the percentage of non-helical signals
      varies among residue types; these percentages agree well between the NMR and
      diffraction data. Samples show minimal evidence of degradation after several
      weeks of NMR data acquisition. Use of a triple resonance scroll resonator probe
      further improves sample stability and enables higher power decoupling, higher
      duty cycles and more advanced 3D experiments to be performed. These initial
      results in cytochrome bo(3) oxidase demonstrate that multidimensional MAS SSNMR
      techniques have sufficient sensitivity and resolution to interrogate selected
      parts of a very large uniformly (13)C,(15)N-labeled membrane protein.

PMID- 16964533
TI  - Towards unambiguous assignment of methyl-containing residues by double and triple
      sensitivity-enhanced HCCmHm-TOCSY experiments.
AB  - Chemical shift assignment of methyl-containing residues is essential in protein
      NMR spectroscopy, as these residues are abundant in protein interiors and provide
      the vast majority of long-range NOE connectivities for structure determination.
      These residues also constitute an integral part of hydrophobic cavities, the
      surroundings for many enzymatic reactions. Here we present a powerful strategy
      for the assignment of methyl-containing residues in a uniformly 13C/15N double
      labeled protein sample. The approach is based on novel four-dimensional HCCmHm
      TOCSY experiments, two of them utilizing gradient selection and sensitivity
      enhancement in all three indirectly detected dimensions. Regardless of the number
      of dimensions, the proposed experiments can be executed using only one transient
      per FID, providing outstanding resolution and sensitivity. A complete assignment
      of the 51 methyl-containing residues in the 16 kDa Mus musculus coactosin was
      accomplished using a four-dimensional HCCmHm-TOCSY spectrum recorded in 16 hours.

PMID- 16964534
TI  - Identification of individual protein-ligand NOEs in the limit of intermediate
      exchange.
AB  - Interactions of proteins with small molecules or other macromolecules play key
      roles in many biological processes and in drug action, and NMR is an excellent
      tool for their structural characterization. Frequently, however, line broadening
      due to intermediate exchange completely eliminates the signals needed for
      measuring specific intermolecular NOEs. This limits the use of NMR for detailed
      structural studies in such kinetic situations. Here we show that an optimally
      chosen excess of ligand over protein can reduce the extent of line broadening for
      both the ligand and the protein. This makes observation of ligand resonances
      possible but reduces the size of the measurable NOEs due to the residual line
      broadening and the non-stoichiometric concentrations. Because the solubility of
      small molecule drug leads are often limited to high micromolar concentrations,
      protein concentrations are restricted to even lower values in the low micromolar
      range. At these non-stoichiometric concentrations and in the presence of
      significant residual line broadening, conventional NOESY experiments very often
      are not sensitive enough to observe intermolecular NOEs since the signals
      inverted by the NOESY preparation pulse sequence relax prior to significant NOE
      build up. Thus, we employ methods related to driven NOE spectroscopy to
      investigate protein-ligand interactions in the intermediate exchange regime. In
      this approach, individual protein resonances are selectively irradiated for up to
      five seconds to build up measurable NOEs at the ligand resonances. To enable
      saturation of individual protein resonances we prepare deuterated protein samples
      selectively protonated at a few sites so that the 1D (1)H spectrum of the protein
      is resolved well enough to permit irradiation of individual protein signals,
      which do not overlap with the ligand spectrum. This approach is suitable for
      measuring a sufficiently large number of protein-ligand NOEs that allow
      calculation of initial complex structures, suitable for structure-based
      optimization of primary drug leads obtained from high-throughput screening. The
      method was applied to measure individual intermolecular NOEs between the anti
      apoptotic protein Bcl-xL at 25 microM and a "first generation" small-molecule
      ligand, for which the spectrum is entirely broadened at stoichiometric
      concentrations. This approach is general and can also be used to characterize
      protein-protein or protein-nucleic-acid complexes.

PMID- 16964535
TI  - Correlation of Bispectral Index with Glasgow Coma Score in mild and moderate head
      injuries.
AB  - BACKGROUND: Bispectral Index (BIS) derived from electroencephalogram (EEG) is
      primarily developed to monitor the depth of unconsciousness. Recent evidence
      suggests that BIS may also help in the detection of cerebral ischemia and
      prognostication of outcome of traumatic brain injury (TBI). The present study was
      designed to investigate the correlation between Glasgow Coma Score (GCS) and BIS
      in mild and moderate head injury. METHODS: In 29 patients with mild (GCS 13-15)
      and moderate (GCS 9-12) head injuries who underwent craniotomy, GCS and BIS were
      measured before surgery, after surgery and once a day for the first 10 days.
      RESULTS: A significant correlation was found between GCS and BIS in the data sets
      from all the patients (r = 0.67; p < 0.001). Mean BIS values increased with
      increasing GCS scores. However, the scatter of BIS values for any GCS score was
      high limiting the value of BIS in predicting GCS. Mean BIS values were
      significantly different between mild and moderate head injuries [65.7 +/- 16.1
      vs. 85.7 +/- 6.1, p = 0.006]. CONCLUSION: In patients with mild and moderate head
      injury, significant correlation exists between GCS and BIS. But the high degree
      of scatter of BIS values for any given GCS score limits its use as a monitor of
      depth of coma in TBI. Further studies are required to understand the relation
      between BIS algorithm and cerebral electrical activity following TBI to define
      the role of BIS as an electrophysiological correlate of consciousness in TBI.

PMID- 16964536
TI  - Advanced course for doctors as Departmental IT Network Administrators in
      anesthesia and intensive care units.
AB  - The design and administration of a departmental computer network (Local Area
      Network) in anesthesiology and intensive care offer the opportunity to manage
      clinical information and control the work-flow. To improve the local network,
      after basic design, intelligence is necessary to maintain its efficiency. For
      this reason the role of a medical administrator of the network is fundamental
      because he is a qualified figure who recognizes the most important
      characteristics that a network must have, knows the users of the system,
      represents a valid consultant for the technician that has to build the network,
      and is able to face possible breakdowns. This paper illustrates the structure of
      a course to train a medical network administrator in anesthesiology and critical
      care.

PMID- 16964537
TI  - Scientific meeting of the American Institute for Psychoanalysis. The canary in
      the mind: on the fate of dreams in psychoanalysis and in contemporary culture.

PMID- 16964539
TI  - Forced migration, adolescence, and identity formation.
AB  - Adolescence is a complex biopsychosocial phenomenon. All the inner-subjective
      changes in adolescents take place within the context of a specific social
      environment, which offers the necessary ideological setting that adolescents must
      confront in the course of their identity formation. Forced migration creates
      conditions under which the adolescent Ego may be traumatized more easily,
      resulting in the development of defensive mechanisms, which may interfere with
      the natural process of identity formation. The aim of this paper is to
      investigate how a traumatic situation such as forced migration may affect the
      mechanisms of identity formation in adolescence. For this purpose, clinical
      material, consisting of two cases of psychoanalytical psychotherapy of
      adolescents who were forced to immigrate to Greece, is presented and discussed in
      a psychoanalytical theoretical framework, along with the historical-sociological
      background.

PMID- 16964540
TI  - The formation and development of individual and ethnic identity: insights from
      psychiatry and psychoanalytic theory.
AB  - This paper describes the concept of identity formation, examining the historical
      development of identity, particularly ethnic identity. The author distinguishes
      the normative developmental achievement of self and group identity with
      pathological identity diffusion due to an earlier attachment disorder. The
      clinical case of a young male's experience of his Persian family's immigration to
      a new host country details the challenges encountered in ethnic identity
      formation and its interference in consolidating this ongoing process. The
      complicated task of self identity formation during this phase of development in
      the face of parental unresolved and ambivalent attitudes toward their own sense
      of threatened self and group identity diffusion is discussed. Parental
      intrapsychic conflict combined with environmental conflict such as racism,
      prejudice, and more recent paranoia toward Middle Eastern immigrant families
      interferes further with the normal identity formation process. The paper
      elaborates the compromised bicultural identity of a youngster who struggles
      through his developmental life phases.

PMID- 16964541
TI  - The role of tacrolimus in inflammatory bowel disease: a systematic review.
AB  - Therapeutic management of inflammatory bowel disease remains beyond the limits of
      conventional therapy in many cases. Novel therapies used include tacrolimus, a
      new powerful immunosuppressive drug, employed in some case reports and a few
      studies that have tried to evaluate its effectiveness in Crohn's disease and
      ulcerative colitis with promising results, but its role in the management of
      inflammatory bowel disease remains controversial. We performed a systematic
      review that analyzed a total of 23 reported experiences in 286 patients with
      inflammatory bowel disease treated with tacrolimus. Although most of the
      published studies are uncontrolled, short, and heterogeneous, promising results
      have been obtained in fistulizing disease, unresponsive cases of both ulcerative
      colitis and Crohn's disease, and even extraintestinal manifestations. The overall
      outcome was good enough to consider tacrolimus as a rationale therapeutic option.
      However, comparative studies with standard therapeutic options like infliximab
      are needed to assess the correct role that tacrolimus may play in these patients.

PMID- 16964542
TI  - Central retinal vein thrombosis in a patient with ulcerative colitis.

PMID- 16964543
TI  - HFE mutations analysis of Turkish patients with nonalcoholic steatohepatitis.

PMID- 16964544
TI  - Plasma calprotectin levels in patients suffering from acute pancreatitis.
AB  - Calprotectin (Cal) concentration is elevated in acute inflammatory reactions and
      its increase in the plasma suggests a diagnostic potential for Cal assay. This
      study aimed (a) to evaluate the Cal plasma levels in patients suffering from
      acute pancreatitis (AP) and (b) to assess whether early assay of Cal plasma
      levels can be helpful in assessment of the severity of AP. Forty-six consecutive
      patients, median age 45 years, suffering from a first attack of AP were recruited
      at two medical centers. Data collected on admission included age, sex, delay
      between pain onset and admission, and Glasgow score. A severe outcome was defined
      according to the Atlanta criteria. AP was defined as edematous or necrotic
      according to the CT findings. Plasma Cal and serum C reactive protein (CRP) were
      assayed in all patients within the first 24 hr after hospitalization. Sixty
      subjects suffering from blood hypertension were recruited as controls. Plasma Cal
      was measured by a commercial ELISA system. In all AP patients and in none of the
      controls, plasma Cal concentration was higher than the normal limit. Cal values
      in AP patients were significantly higher than in controls (P < 0.0001). There was
      not a statistically significant difference in Cal values between patients with
      severe and patients with mild AP. Plasma Cal values did not differ in necrotizing
      and edematous AP. During the follow-up plasma Cal was reassayed in six of the
      patients with abdominal fluid collection and the values were higher in the two
      patients with infected necrosis. We conclude that plasma Cal is elevated in
      patients with AP but it is not a useful marker for early prediction of
      pancreatitis severity. Further studies could evaluate its usefulness in
      pancreatic infected necrosis.

PMID- 16964545
TI  - Spontaneous rupture of a true splenic cyst diagnosed by laparoscopy.

PMID- 16964546
TI  - Brief report: no evidence for parvovirus B19 or hepatitis E virus as a cause of
      acute liver failure.
AB  - Viral hepatitis A and B are known to cause acute liver failure. While nearly 20%
      of acute liver failure cases are of indeterminate etiology, screening for other
      viruses has not been uniformly performed. We looked for evidence for parvovirus
      B19 and hepatitis E virus in sera from U.S. acute liver failure patients. For
      B19, 78 patients' sera, including 34 with indeterminate etiology, were evaluated
      by DNA dot-blot hybridization, reverse transcription polymerase chain reaction,
      and enzyme-linked immunosorbent assay for immunoglobin G and M antibodies; none
      showed evidence for infection.

PMID- 16964547
TI  - Clostridium sp. bacteremia in a cirrhotic patient with an unresecable
      hepatocellular carcinoma: as fatal as we thought?

PMID- 16964548
TI  - Serum iron levels and hepatic iron overload in patients with nonalcoholic
      steatohepatitis.

PMID- 16964549
TI  - Increased protein expression of matrix metalloproteinases -1, -3, and -9 and TIMP
      1 in patients with gluten-sensitive enteropathy.
AB  - Gluten-sensitive enteropathy is characterized by small intestinal damage. The
      pathogenic mechanisms involved are not precisely understood. There is recent
      interest in the possibility that matrix metalloproteinases might play a
      pathogenic role. Using immunohistochemistry technique, we examined the protein
      expression of matrix metalloproteinases-1, -3, and -9 and the tissue inhibitor
      metalloproteinase-1 in duodenal biopsies from 30 patients with celiac disease and
      dermatitis herpetiformis. We demonstrated that the percentage of cells expressing
      these enzymes and their inhibitor in all patients was significantly greater than
      in the normal controls (P < 0.0001). This was evident even in patients with a
      minimal lesion but was most marked in patients with severe damage, mirroring the
      degree of inflammation in the small intestinal tissue. The increased expression
      of these enzymes and their inhibitor in the duodenal mucosa of patients with
      gluten-sensitive enteropathy suggests a role for these enzymes in the tissue
      remodeling which is a feature of these disorders.

PMID- 16964550
TI  - Sirolimus monotherapy versus sirolimus in combination with steroids and/or MMF
      for immunosuppression after liver transplantation.
AB  - Calcineurin inhibitor (CI)-associated renal dysfunction has emerged as a major
      cause of morbidity and mortality after liver transplantation. In this
      retrospective study, we compared the efficacy, safety, and renal protective
      effect of sirolimus monotherapy (Group A; n = 26) with sirolimus in combination
      (Group B; n = 34) with steroids and/or mycophenolate mofetil (MMF) in liver
      transplant recipients who were switched from CI. Patients were switched abruptly
      or over a period of 2-4 weeks and followed for 17 +/- 10 months. Preconversion
      renal biopsies in five of six patients showed histological features consistent
      with CI nephrotoxicity. Serum creatinine increased in the year prior to
      conversion from 1.7 +/- 0.4 to 2.1 +/- 0.7 mg/dl (P = 0.009) and improved
      thereafter (1 month, 1.7 +/- 0.6, P < 0.001; 6 months, 1.6 +/- 0.5, P < 0.001;
      last follow-up, 1.7 +/- 0.9, P = 0.02); only four patients showed a significant
      decline in renal function after conversion. Seven (11.3%) patients experienced
      acute rejection (Group A, two; Group B, five; P = NS) and this resulted in the
      discontinuation of sirolimus in one patient. Fifty-four adverse events occurred
      in 40 (67%) patients, with similar numbers of adverse events in Group A and Group
      B. Most episodes of rejection (5/7; 71%), adverse events (45/54; 83%), and
      discontinuations (5/8; 63%) occurred within 6 months of conversion. We conclude
      that both sirolimus monotherapy and sirolimus in combination with prednisone
      and/or MMF are efficacious and safe in liver transplant recipients. Conversion to
      sirolimus was associated with an immediate improvement in renal function that was
      sustained during the follow-up.

PMID- 16964551
TI  - Detection of cellular immunity to rabies antigens in human vaccinees.
AB  - A nonradioactive multi-parameter flow cytometry assay was developed to identify
      antigen-specific lymphocytes in human subjects previously vaccinated against
      rabies virus and was subsequently compared to the standard tritiated thymidine
      method. A cell tracking dye, carboxyfluorescein succinimidyl ester, was used in
      combination with surface label for CD4 and CD8 cells in order to determine the
      response of lymphocytes to killed rabies virus in an antigen recall assay. The
      rabies virus-specific lymphocyte response was compared to the humoral immune
      response in each of ten vaccinated and five non-vaccinated subjects. Lymphocyte
      responses to rabies virus were observed in all ten vaccinated subjects; some
      noted as early as 3 days after stimulation while others were not until 7 days
      after stimulation. There was good agreement between the proliferation index of
      the CFSE assay and the simulation index of the [3H]thymidine assay (kappa
      statistic=0.73). An inverse relationship was detected between the level of rabies
      virus neutralizing antibody (RVNA) and the lymphocyte response to inactivated
      rabies virus in the vaccinated subjects. The association between cytokines
      production and level of humoral and cellular response was investigated in four
      representative subjects. Two vaccinated subjects with high proliferation indices
      and low RVNA titers produced Th1 type cytokines to rabies virus stimulation,
      whereas two vaccinated individuals with low proliferation indices and high RVNA
      titers responses did not produce these cytokines.

PMID- 16964552
TI  - Inhibition of alpha nascent polypeptide associated complex protein may induce
      proliferation, differentiation and enhance the cytotoxic activity of human CD8+ T
      cells.
AB  - The molecular mechanisms that control CD8(+) T cell proliferation and
      differentiations are poorly understood. Consequently, better understanding of the
      molecular pathways that regulate these processes may have an impact on the
      numbers and efficiency of antigen-specific cells that can be generated for
      cellular immunotherapy applications. Using differential display, we previously
      determined that alpha nascent polypeptide associated complex (alpha NAC) was
      identified as a potential target as its protein expression was found to be down
      regulated as differentiation progressed in cultured human CD8(+) T cells. Here
      anti-sense technology was used to further investigate the role which alpha NAC
      may play in proliferation and differentiation. Human purified CD8(+) T cells were
      cultured in the presence of sense, non-sense and anti-sense oligonucleotides
      against the mRNA of alpha NAC. We reported that in the presence of anti-sense
      oligonucleotides expanded CD8(+) T cells exhibited higher levels of
      differentiation and activation markers and also increased proliferation response
      compared to cells cultured with sense-oligonucleotides. Furthermore, the
      functional cytotoxicity of CD8(+) T cells cultured with anti-sense was increased
      to 66% (+/-4.7%) compared to 42% (+/-3.2%) in cells expanded in the presence of
      oligonucleotides controls. Taken together, our results demonstrated that
      inhibition of alpha NAC protein induced not only cell proliferation but also
      differentiation and cytotoxic activity of CD8(+) T cells.

PMID- 16964553
TI  - Polymorphisms in the repeat long regions of oncogenic and attenuated pathotypes
      of Marek's disease virus 1.
AB  - The nucleotide sequences of the terminal repeat long (TR(L)) and internal repeat
      long regions (IR(L)) in the genomes of 13 strains of Marek's disease virus type 1
      (MDV-1) were determined and represent the largest collection of sequencing data
      from a contiguous region (12.8 kb) in the serotype 1 genomes. The collection of
      strains used in this study has been well characterized with respect to their
      virulence and contains members of each pathotype (4 attenuated, 1 mildly
      virulent, 3 virulent, 2 very virulent and 3 very virulent plus). It has
      previously been reported that two loci (meq and RLORF4) in the RL regions are
      likely to encode virulence factors based on comparative genomic studies involving
      vaccine and virulent strains. Additional studies using knockout mutants have
      provided stronger evidence that indeed RLORF4 and meq or the overlapping genes 23
      kD and RLORF6 are involved in virulence. In this report, we provide evidence that
      additional open reading frames (ORFs) in the RL regions differ significantly
      between the extremes of the pathotypes (attenuated vs. nonattenuated). A deletion
      of 10 base pairs has been identified in RLORF12 from two attenuated strains
      CVI988 BP-5, p48 and RM-1, p40; and the lower virulence strain JM/102W. A
      deletion of 40 bp was also identified in RLORF4 of the attenuated strain R2/23,
      passage 106. A 177 bp insertion within the meq loci has been identified in most
      of the attenuated strains examined. Interestingly, R2/23 did not contain this
      insertion but instead truncated proteins are predicted for the three overlapping
      ORFs (meq, 23 kD and RLORF6) due to a frameshift mutation. Single nucleotide
      polymorphisms (SNPs), which loosely partition between attenuated and
      nonattenuated strains, have been identified in the ORFs encoding RLORF12, RLORF8,
      meq, 23 kD, RLORF6, RLORF4, RLORF3 and ICP0 and three previously unidentified
      short ORFs: MHLS, MLHG and MPSG. Although no single nucleotide polymorphism in
      the RL regions could predict virulence, their overall contribution to virulence
      can now be examined in defined mutants containing additional insertions or
      deletions in ORFs, suspected of encoding virulence factors, identified by this
      research.

PMID- 16964554
TI  - Protein pE120R of African swine fever virus is post-translationally acetylated as
      revealed by post-source decay MALDI mass spectrometry.
AB  - Post-translational modification of proteins is a key regulatory event in many
      cellular processes. African swine fever virus (ASFV) is a large DNA virus that
      contains about 150 open reading frames (ORF) which encode for more than 150
      polypeptides, most of them without assigned function. Two-dimensional gel
      electrophoresis (2DE) followed by Post-Source Decay Matrix-Assisted Laser
      Desorption/Ionization Mass Spectrometry (PSD-MALDI-MS) revealed that ASFV protein
      pE120R, essential for virus transport from assembly sites to plasma membranes, is
      acetylated at the N-terminal Ala residue during infection. To our knowledge, this
      is the first acetylated ASFV protein described and this modification might be
      relevant to ASFV life cycle since many viruses use the acetylation signaling
      pathway as a primary target for viral proteins after infection.

PMID- 16964555
TI  - Identification, phenotypic analysis, and full-length nucleotide sequence of a
      Dutch Coxsackievirus A20 isolate.
AB  - Recombination between (human) enteroviruses is a common event in nature.
      Recently, it has been recognised that this feature has a major impact on the use
      of the live-attenuated polio vaccine during the end stage of polio eradication.
      The constraints for successful recombination between (vaccine-derived)
      polioviruses and human enteroviruses are, however, largely unknown. Here, we
      describe the identification and characterisation of a HEV-C field strain,
      isolated from the stool of a 2-year-old Dutch boy. Serotyping indicated that
      strain 89490 is a variant of strain CAV20a, which is already a variant of the
      prototype CAV20 strain. Amino acid sequence identity of 94.1% for the entire P1
      region, and 92.4% for the major structural protein (VP1) indicates that this
      strain is indeed related to CAV20. However, virus neutralisation and Western blot
      analysis failed to show antigenic homology between the prototype CAV20 strain and
      our field strain. Furthermore, the 89490 field strain, just like the sub
      prototype CAV20a, is able to replicate on RD-cells, while the prototype CAV20 and
      another sub-prototype CAV20b are not. On the basis of the phylogenetic analysis
      of the P2 and P3 region we expect that strain 89490 can act as recombination
      partner for the attenuated poliovirus strains of the Oral Polio Vaccine (OPV).

PMID- 16964556
TI  - Cultural awareness through medical student and refugee patient encounters.
AB  - PURPOSE: This paper presents findings from a qualitative investigation of
      cultural awareness that medical students developed in the context of providing
      medical care to refugees. Our evaluation question was: What kinds of cultural
      awareness and communication lessons do medical students derive from clinical
      encounters with refugee patients? METHODS: Thirty-eight semi-structured
      interviews were conducted to debrief a sample of 27 medical students. A
      multidisciplinary research team analyzed the debriefing texts following an
      interpretive "immersion-crystallization" approach. RESULTS: Three domains in
      cultural awareness training encompassed 13 key lessons or themes. Students
      reported enhanced awareness about the use of interpretation services and cross
      cultural communication. A second set of lessons reflected awareness of the
      refugees' cultural background, and a third learning component involved
      experiences of cultural humility. The refugee plight prompted reflection on the
      students' own culture, and validated the rationale for empathetic care and
      patient empowerment. CONCLUSION: As medical school curricula incorporate more
      cultural diversity training, a patient-based learning approach with selected
      'hands-on' experiences will create opportunities for students to increase their
      cultural sensitivity and competency. This program's experiential model indicates
      that after refugee medical encounters, these beginning medical students reported
      greater awareness of communication issues, and sensitivity toward religious
      values, family patterns, gender roles and ethnomedical treatments. It will be
      important to test these kinds of preceptor/apprenticeship models of cultural
      sensitivity training at later stages of medical training; in order to assess long
      term effects.

PMID- 16964557
TI  - Recovery of the blood pressure - cerebral flow relation after carotid stenting in
      elderly patients.
AB  - BACKGROUND: As a sensitive and convenient means for the cerebral hemodynamic
      monitoring, dynamic cerebral autoregulation testing could be especially useful in
      medical conditions where less invasive diagnostics and therapies are preferred.
      This study analysed the effect of carotid stenting on dynamic autoregulation in
      elderly patients focussing on the relation between blood pressure and cerebral
      blood flow velocity. METHODS: We examined 20 patients age 69 +/- 8 years with
      coexisting cerebrovascular and medical risk factors before and at least six month
      after stenting of severe carotid stenoses. Data were compared to 24 age-matched
      healthy controls. Slow spontaneous oscillations were studied in continuous
      recordings of Transcranial Doppler and beat-to-beat blood pressure. Analysis was
      based on the "high-pass filter model", which predicts a positive phase
      relationship between these oscillations. FINDINGS: Whereas phase shift angles
      were diminished (20.4 +/- 14.1 degrees ) before stenting, after stenting these
      values were significantly increased to normal (48.1 +/- 16.6 degrees ), to the
      level of controls (46.7 +/- 15.9 degrees ). Medical conditions such as coronary
      artery disease, arterial hypertension, and dyslipidemia did not diminish this
      recovery. The level of increase was inversely correlated with the initial
      autoregulatory deficit (r = -0.68) which was largest with insufficient collateral
      blood supply and symptomatic carotid stenoses. CONCLUSIONS: The study showed that
      an impaired cerebral autoregulation may recover after stent-guided carotid
      angioplasty even in the elderly with co-existing medical conditions. In this
      respect to regain vasomotor capability, patients with cerebrovascular risk
      factors seemed to benefit particularly.

PMID- 16964558
TI  - Evaluation of apoptosis in cerebrospinal fluid of patients with severe head
      injury.
AB  - OBJECTIVE: To determine whether sFas, caspase-3, proteins which propagate
      apoptosis, and bcl-2, a protein which inhibits apoptosis, would be increased in
      cerebrospinal fluid (CSF) in patients with severe traumatic brain injury (TBI)
      and to examine the correlation of sFas, caspase-3, and bcl-2 with each other and
      with clinical variables. METHODS: sFas, caspase-3, and bcl-2 were measured in CSF
      of 14 patients with severe TBI on days 1, 2, 3, 5, 7, and 10 post-trauma. The
      results were compared with CSF samples from control patients who had no brain and
      spinal pathology and had undergone spinal anesthesia for some other reason.
      Soluble Fas and bcl-2 were measured by ELISA while caspase-3 was measured
      enzymatically. RESULTS: No sFas, caspase-3, and bcl-2 activities were found in
      CSF of controls, but activities significantly increased in CSF of patients at all
      time points post-trauma (p < 0.01). Caspase-3 significantly correlated to
      intracranial pressure (p = 0.01) and cerebral perfusion pressure (p = 0.04).
      Soluble Fas and caspase-3 peaks coincided on day 5 post-trauma and there was
      significant association between sFas and caspase-3 increase (p = 0.01).
      CONCLUSION: This study indicates a prolonged activation of pro-apoptotic (sFas,
      caspase-3) and anti-apoptotic (bcl-2) proteins after severe TBI in humans. The
      degree of activation of particularly caspase-3 may be related to the severity of
      the injury. Parallel increases of these three molecules may indicate a pivotal
      role of apoptosis in the pathophysiology of post-traumatic brain oedema,
      secondary cell destruction and chronic cell loss following severe TBI and may
      open new targets for post-traumatic therapeutic interventions.

PMID- 16964559
TI  - The role of endoscopic third ventriculostomy in the management of hydrocephalus
      associated with cerebellopontine angle tumours.
AB  - BACKGROUND: Progressive hydrocephalus secondary to cerebellopontine angle tumours
      has been traditionally managed with ventriculo-peritoneal shunting. Endoscopic
      third ventriculostomy provides an alternative treatment option and the success
      rate in this patient group has not previously been reported. METHODS: We report a
      retrospective series of 11 patients with cerebello-pontine angle tumours who
      presented with symptomatic hydrocephalus, or developed hydrocephalus following
      radiosurgery, who underwent endoscopic third ventriculostomy. RESULTS: Seven
      patients (63.6%) remain shunt free. There were no complications following
      endoscopy in any patient. Where the ventriculostomy failed there was no
      additional morbidity. CONCLUSIONS: Endoscopic third ventriculostomy is a low
      morbidity procedure, which avoids the inherent problems of shunts, particularly
      infection and should be considered for patients with hydrocephalus and cerebello
      pontine angle tumours.

PMID- 16964560
TI  - Enantiopure beta3-amino acids-2,2-d2 via homologation of proteinogenic alpha
      amino acids.
AB  - A procedure for the synthesis of enantiopure beta3-amino acids from proteinogenic
      alpha-amino acids, developed by our group a few years ago, has been modified to
      enable the production of C-2 fully deuterated, C-protected beta3-amino acids and,
      even more important, the synthesis of valuable deuterium labelled N(Boc)
      protected chiral synthons, such as 2-aminoalcohols, 2-aminoiodides, and beta3
      amino nitriles.

PMID- 16964561
TI  - The necessity of functional proteomics: protein species and molecular function
      elucidation exemplified by in vivo alpha A crystallin N-terminal truncation.
AB  - Ten years after the establishment of the term proteome, the science surrounding
      it has yet to fulfill its potential. While a host of technologies have generated
      lists of protein names, there are only a few reported studies that have examined
      the individual proteins at the covalent chemical level defined as protein species
      in 1997 and their function. In the current study, we demonstrate that this is
      possible with two-dimensional gel electrophoresis (2-DE) and mass spectrometry by
      presenting clear evidence of in vivo N-terminal alpha A crystallin truncation and
      relating this newly detected protein species to alpha crystallin activity
      regulation by protease cleavage in the healthy young murine lens. We assess the
      present state of technology and suggest a shift in resources and paradigm for the
      routine attainment of the protein species level in proteomics.

PMID- 16964562
TI  - Development and evaluation of different methods to assess download and display
      time of image web systems.
AB  - OBJECTIVES: The aim of this study was to develop and verify different methods of
      measuring time-to-display (TTD) for radiological images with image web systems
      (IWS). The process should be automatable in order to repeatedly perform a large
      number of measurements without human interaction. MATERIALS AND METHODS: Three
      methods were defined and compared with respect to usability, stability, and
      quality of results. Method 1 was based on Windows 2000 Performance Monitor,
      whereas method 2 employed phototransistors taped to the screen and connected to a
      separate PC. A software tool developed for method 3, which used Windows
      application programming interface (API) function, calls to read the color code
      assigned to specific pixels on the screen. RESULTS: Method 3 proved to be the
      most reliable and easy to automate. The accuracy is practically equivalent to
      method 2, but it proved to be far more automatable. Method 1 produced the largest
      mean error, was easily disturbed, but was also easy to set up and provided
      additional insights into the system's architecture especially if combined with
      method 3. CONCLUSIONS: To measure the performance of image distribution systems,
      any of these methods can be used, but method 3 proved to be superior.

PMID- 16964565
TI  - Perceived barriers to treatment and psychotherapy attendance in child community
      mental health centers.
AB  - Poor psychotherapy attendance is a major problem facing most child community
      mental health centers. However, post-treatment perspectives on reasons for
      premature termination are rarely sought from either families or clinicians. In
      the present study, we collected parent data and clinician data regarding 72 and
      153 clients, respectively, from four child and adolescent community mental health
      centers serving diverse families. Problems regarding (a) the perceived relevance
      of treatment and (b) the quality of the therapist-family relationship emerged as
      the two most consistent factors related to premature dropout. Possible
      interventions to increase psychotherapy attendance are highlighted.

PMID- 16964563
TI  - Vasoactive intestinal polypeptide suppressed experimental autoimmune
      encephalomyelitis by inhibiting T helper 1 responses.
AB  - Vasoactive intestinal peptide (VIP) has been found to act as a potent anti
      inflammatory factor through regulating the production of both anti- and pro
      inflammatory mediators and promoting Th2-type responses. In this study, we used
      myelin oligodendrocyte glycoprotein-induced experimental autoimmune
      encephalomyelitis (EAE) model in C57BL/6 mice to investigate the potential
      effects of VIP on multiple sclerosis. Our results showed that in vivo treatment
      of EAE-induced mice with VIP had great protective benefit at both clinical and
      histological levels. Disease suppression was associated with the inhibition of T
      cells proliferation, shifting of the immune response toward a Th2-type response
      and influencing the expression of pro-inflammatory cytokines including IFN-gamma,
      IL-6 and IL-2 as well as chemotactic factors such as RANTES. In conclusion, the
      study provides evidence that VIP had great protective effect on EAE through its
      inhibition actions on pathogenic T cells and through a specific effect on the Th1
      response.

PMID- 16964566
TI  - Genome constitutions of Hystrix patula, H. duthiei ssp. duthiei and H. duthiei
      ssp. longearistata (Poaceae: Triticeae) revealed by meiotic pairing behavior and
      genomic in-situ hybridization.
AB  - Genomic constitutions of three taxa of Hystrix Moench, H. patula, H. duthiei ssp.
      duthiei and H. duthiei ssp. longearistata, were examined by meiotic pairing
      behavior and genomic in-situ hybridization. Meiotic pairing in hybrids of H.
      patula x Pseudoroegneria spicata (St), H. patula x Elymus wawawaiensis (StH), H.
      patula x H. duthiei ssp. longearistata, H. patula x Psathyrostachys huashanica
      (Ns ( h )), H. duthiei ssp. duthiei x Psa. huashanica, H. duthiei ssp.
      longearistata x Psa. huashanica, Leymus multicaulis (NsXm) x H. duthiei ssp.
      longearistata averaged 6.53, 12.83, 1.32, 0.29, 5.18, 5.11 and 10.47 bivalents
      per cell, respectively. The results indicate that H. patula has the StH genome
      and H. duthiei ssp. duthiei and H. duthiei ssp. longearistata have the NsXm
      genome. Results of genomic in-situ hybridization analysis strongly supported the
      chromosome pairing data; therefore it is concluded that the type species of
      Hystrix, H. patula, should be included in Elymus, and that H. duthiei ssp.
      duthiei and H. duthiei ssp. longearistata should be transferred to Leymus.

PMID- 16964567
TI  - MLH1-focus mapping in birds shows equal recombination between sexes and diversity
      of crossover patterns.
AB  - Using immunolocalization of the mismatch-repair protein MLH1 in oocytes and
      spermatocytes of the Japanese quail and the zebra finch, we estimated the average
      amount of recombination in each sex of both species. In each case the number of
      MLH1 foci is statistically equivalent in males and females and the resulting sex
      averaged map lengths are 2800 cM in the Japanese quail and 2275 cM in the zebra
      finch. In the Japanese quail the MLH1 foci are regularly distributed along the
      macrobivalents and recombination rates per Mb pair are somewhat lower compared to
      the chicken. In the zebra finch the MLH1 foci on the macrobivalents are
      substantially reduced in number relative to the Japanese quail and they show
      remarkable localization in both sexes. It is proposed that the lack of sex
      dependent differences in recombination might be an extended feature among birds
      and that the different recombination patterns observed here reflect different
      controls of crossing over in spite of similarities regarding karyotypic asymmetry
      and DNA content. We discussed possible causes of the differences between birds
      and mammals, which show sex-dependent recombination differences.

PMID- 16964568
TI  - A novel family of repetitive DNA sequences amplified site-specifically on the W
      chromosomes in Neognathous birds.
AB  - A novel family of repetitive DNA sequences was molecularly cloned from ApaI
      digested genomic DNA of two Galliformes species, Japanese quail (Coturnix
      japonica) and guinea fowl (Numida meleagris), and characterized by chromosome in
      situ hybridization and filter hybridization. Both the repeated sequence elements
      produced intensely painted signals on the W chromosomes, whereas they weakly
      hybridized to whole chromosomal regions as interspersed-type repetitive
      sequences. The repeated elements of the two species had high similarity of
      nucleotide sequences, and cross-hybridized to chromosomes of two other
      Galliformes species, chicken (Gallus gallus) and blue-breasted quail (Coturnix
      chinensis). The nucleotide sequences were conserved in three other orders of
      Neognathous birds, the Strigiformes, Gruiformes and Falconiformes, but not in
      Palaeognathous birds, the Struthioniformes and Tinamiformes, indicating that the
      repeated sequence elements were amplified on the W chromosomes in the lineage of
      Neognathous birds after the common ancestor diverged into the Palaeognathae and
      Neognathae. They are components of the W heterochromatin in Neognathous birds,
      and a good molecular cytogenetic marker for estimating the phylogenetic
      relationships and for clarifying the origin of the sex chromosome heterochromatin
      and the process of sex chromosome differentiation in birds.

PMID- 16964569
TI  - Genomic affinities between maize and Zea perennis using classical and molecular
      cytogenetic methods (GISH-FISH).
AB  - In this study we have analysed and compared the genomic composition, meiotic
      behaviour, and meiotic affinities of Zea perennis and Zea mays ssp. mays. To do
      so we studied the parental taxa and the interspecific hybrid Zea perennis x Zea
      mays ssp. mays, using classical cytogenetic methods, as well as GISH and FISH.
      GISH enabled us to recognize the genomic source of each chromosome involved in
      the meiotic configurations of this hybrid, and established the genomic affinities
      between their parental species. The results obtained here reinforce the
      hypothesis of the amphiploid origin of Zea perennis and, together with previous
      research, indicate that the chromosomes with divergent repetitive sequences in
      maize and Zea luxurians could be the remnants of a relict parental genome not
      shared with Zea perennis.

PMID- 16964570
TI  - Tandem chromosome fusions in karyotypic evolution of Muntiacus: evidence from M.
      feae and M. gongshanensis.
AB  - The muntjacs (Muntiacus, Cervidae) are famous for their rapid and radical
      karyotypic diversification via repeated tandem chromosome fusions, constituting a
      paradigm for the studies of karyotypic evolution. Of the five muntjac species
      with defined karyotypes, three species (i.e. Muntiacus reevesi, 2n = 46; M. m.
      vaginalis, 2n = 6/7; and M. crinifrons, 2n = 8/9) have so far been investigated
      by a combined approach of comparative chromosome banding, chromosome painting and
      BAC mapping. The results demonstrated that extensive centromere-telomere fusions
      and a few centric fusions are the chromosomal mechanisms underlying the
      karyotypic evolution of muntjacs. Here we have applied the same approach to two
      additional muntjac species with less well-characterized karyotypes, M. feae (2n =
      14 male ) and M. gongshanensis (2n = 8 female). High-resolution G-banded
      karyotypes for M. feae and M. gongshanensis are provided. The integrated analysis
      of hybridization results led to the establishment of a high-resolution
      comparative map between M. reevesi, M. feae, and M. gongshanensis, proving that
      all tandem fusions underpinning the karyotypic evolution of these two muntjac
      species are also centromere-telomere fusions. Furthermore, the results have
      improved our understanding of the karyotypic relationships of extant muntjac
      species and provided compelling cytogenetic evidence that supports the view that
      M. crinifrons, M. feae, and M. gongshanensis should each be treated as a distinct
      species.

PMID- 16964571
TI  - Cattle rob(1;29) originating from complex chromosome rearrangements as revealed
      by both banding and FISH-mapping techniques.
AB  - Sixteen carriers of rob(1;29) (one of which was homozygous) from six different
      breeds (four Italian and two Portuguese), two heterozygous carriers of
      rob(26;29), three river buffaloes and two sheep were cytogenetically investigated
      in this study by using banding and FISH-mapping techniques (the latter only in
      cattle and river buffalo). Single- and dual- colour FISH were used with bovine
      probes containing both INRA143 (mapping proximally to BTA29) and bovine satellite
      (SAT) DNA SAT I, SAT III and SAT IV (mapping at the centromeric regions of cattle
      chromosomes). The combined use of these probes, the comparison of rob(1;29) with
      the dicentric rob(26;29) and with both river buffalo and sheep chromosomes
      (biarmed pairs) allowed us to hypothezise that rob(1;29) originated from complex
      chromosomal rearrangements through at least three sequential events: (a) centric
      fusion with the formation of a dicentric chromosome; (b) formation of a
      monocentric chromosome with loss of SAT I from both BTA1 and BTA29, most of SAT
      IV from BTA29 and, probably, some repeats of SAT III from BTA1; (c) double
      pericentric inversion or, more probably, a chromosome transposition of a small
      chromosome segment containing INRA143 from proximal p-arms to proximal q-arm of
      the translocated chromosome.

PMID- 16964572
TI  - Construction of a highly enriched marsupial Y chromosome-specific BAC sub-library
      using isolated Y chromosomes.
AB  - The Y chromosome is perhaps the most interesting element of the mammalian genome
      but comparative analysis of the Y chromosome has been impeded by the difficulty
      of assembling a shotgun sequence of the Y. BAC-based sequencing has been
      successful for the human and chimpanzee Y but is difficult to do efficiently for
      an atypical mammalian model species (Skaletsky et al. 2003, Kuroki et al. 2006).
      We show how Y-specific sub-libraries can be efficiently constructed using DNA
      amplified from microdissected or flow-sorted Y chromosomes. A Bacterial
      Artificial Chromosome (BAC) library was constructed from the model marsupial, the
      tammar wallaby (Macropus eugenii). We screened this library for Y chromosome
      derived BAC clones using DNA from both a microdissected Y chromosome and a flow
      sorted Y chromosome in order to create a Y chromosome-specific sub-library. We
      expected that the tammar wallaby Y chromosome should detect approximately 100
      clones from the 2.2 times redundant library. The microdissected Y DNA detected 85
      clones, 82% of which mapped to the Y chromosome and the flow-sorted Y DNA
      detected 71 clones, 48% of which mapped to the Y chromosome. Overall, this
      represented a approximately 330-fold enrichment for Y chromosome clones. This
      presents an ideal method for the creation of highly enriched chromosome-specific
      sub-libraries suitable for BAC-based sequencing of the Y chromosome of any
      mammalian species.

PMID- 16964573
TI  - Genome size, karyotype, meiosis and a novel extra chromosome in Torenia
      fournieri, T. baillonii and their hybrid.
AB  - Torenia is a suitable model plant to study plant fertilization because of its
      protruding embryo sac. However, information on the genomes and chromosomes of
      this species is limited. We determined the genome sizes of T. fournieri Linden
      and T. baillonii Godefr as 1.71 pg x 10(8) bp and 1.67 x 10(8) bp, respectively.
      The small genome size of these species suggests their superiority as the targets
      for molecular cloning studies. Furthermore, karyotypes of T. fournieri and T.
      baillonii were determined using FISH probed with 5S rDNA, 45S rDNA and species
      specific centromere repetitive sequences. Although the two species have similar
      genome size, number of chromosomes, centromere repeats and 5S rDNA loci were
      varied. Observation of meiosis in the F(1) hybrid revealed that all chromosomes
      except one of T. fournieri paired well with the chromosomes of T. baillonii
      throughout the entire length of the chromosomes including species-specific
      centromeric regions. One exceptional chromosome of T. fournieri behaved as a
      univalent and was not always required for gametogenesis. The present results
      provide the basis for the molecular genetics in Torenia.

PMID- 16964574
TI  - Identification of all pachytene bivalents in the common shrew using DAPI-staining
      of synaptonemal complex spreads.
AB  - A major problem in studies of synaptonemal complexes (SC) is the difficulty in
      distinguishing individual chromosomes. This problem can be solved combining SC
      immunostaining with FISH of chromosome-specific sequences. However, this
      procedure is expensive, time-consuming and applicable only to a very limited
      number of species. In this paper we show how a combination of SC immunostaining
      and DAPI staining can allow identification of all chromosome arms in surface
      spreads of the SC of the common shrew (Sorex araneus L.). Enhancement of
      brightness and contrast of the images with photo editing software allowed us to
      reveal clear DAPI-positive and negative bands with relative sizes and positions
      similar to DAPI landmarks on mitotic metaphase chromosomes. Using FISH with DNA
      probes prepared from chromosome arms m and n we demonstrated correct recognition
      of the chromosomes mp and hn on the basis of their DAPI pattern. We show that the
      approach we describe here may be applied to other species and can provide an
      important tool for identification of individual bivalents in pachytene surface
      spreads.

PMID- 16964575
TI  - Complex evolution of X and Y autosomal translocations in the giant mole-rat,
      Cryptomys mechowi (Bathyergidae).
AB  - Cross-species chromosome painting was used to determine homologous chromosomal
      regions between two species of mole-rat, the naked mole-rat, Heterocephalus
      glaber (2n = 60), and the giant mole-rat, Cryptomys mechowi (2n = 40), using flow
      sorted painting probes representative of all but two of the H. glaber chromosomal
      complement. In total 43 homologous regions were identified in the C. mechowi
      genome. Eight H. glaber chromosomes are retained in toto in C. mechowi, and 13
      produce two or more signals in this species. The most striking difference in the
      karyotypes of the two taxa concerns their sex chromosomes. The H. glaber painting
      probes identified a complex series of translocations that involved the
      fractionation of four autosomes and the subsequent translocation of segments to
      the sex chromosomes and to autosomal partners in the C. mechowi genome. An
      intercalary heterochromatic block (IHB) was detected in sex chromosomes of C.
      mechowi at the boundary with the translocated autosomal segment. We discuss the
      likely sequence of evolutionary events that has led to the contemporary
      composition of the C. mechowi sex chromosomes, and consider these in the light of
      prevailing views on the genesis of sex chromosomes in mammals.

PMID- 16964576
TI  - Causes of B chromosome variant substitution in the grasshopper Eyprepocnemis
      plorans.
AB  - We have analysed B chromosome frequency for three consecutive years, B
      transmission rate at population and individual levels, clutch size, egg fertility
      and embryo-adult viability in a natural population of the grasshopper
      Eyprepocnemis plorans containing two different B chromosome variants, i.e. B(2)
      and B(24), the second being derived from the first and having replaced it in
      nearby populations. From 2002 to 2003 the relative frequency of both variants
      changed, although the differences did not reach significance. A mother-offspring
      analysis showed no significant effect of any of the two B variants on clutch
      size, egg fertility or embryo-adult viability, but B(24) was more efficiently
      transmitted than B(2) through males from the 2002 season, which explains the
      observed frequency change. Controlled crosses, at individual level, showed
      significant drive through some females for B(24) but not for B(2), suggesting
      that this difference in transmission rate might also be important for the
      substitution process. The analysis of relative fitness for B(2) and B(24)
      carriers for all fitness components, as a whole, showed a significantly better
      performance of B(24)-carrying individuals, suggesting that the cumulative effect
      of these slight differences might contribute to the replacement of B(2) by B(24).

PMID- 16964577
TI  - Keeping the memory of smallpox virus.
AB  - Smallpox virus eradication was one of the greatest successes of the 20th century.
      Moreover, the quest to combat its use in biological warfare, has fueled efforts
      to understand residual immune memory and to develop new animal models by the
      scientific community. Although the literature is full of animal studies of
      vaccinia virus infection, continuing efforts have helped to increase our
      knowledge regarding humoral and cellular memory to non-persistent pathogens and
      to study factors that might influence further vaccination strategies in humans.
      In addition, the potent immunostimulatory action of poxvirus vectors has led to
      development and evaluation of new-generation vaccine candidates, which will be
      discussed in this review.

PMID- 16964578
TI  - Anthrax vaccines: Pasteur to the present.
AB  - Anthrax has been a major cause of death in grazing animals and an occasional
      cause of death in humans for thousands of years. Since the late 1800s there has
      been an exceptional international history of anthrax vaccine development. Due to
      animal vaccinations, the rate of infection has dropped dramatically. Anthrax
      vaccines have progressed from uncharacterized whole-cell vaccines in 1881, to
      pXO2-negative spores in the 1930s, to culture filtrates absorbed to aluminum
      hydroxide in 1970, and likely to recombinant protective antigen in the near
      future. Each of these refinements has increased safety without significant loss
      of efficacy. The threat of genetically engineered, antibiotic and vaccine
      resistant strains of Bacillus anthracis is fueling hypothesis-driven research and
      global techniques--including genomics, proteomics and transposon site
      hybridization--to facilitate the discovery of novel vaccine targets. This review
      highlights historical achievements and new developments in anthrax vaccine
      research.

PMID- 16964579
TI  - Brucella as a biological weapon.
AB  - Brucella has traditionally been considered a biological weapon. It was the
      subject of extensive offensive research in the past, and still belongs to
      category B pathogens on most lists. Its propensity for airborne transmission and
      induction of chronic debilitating disease requiring combined antibiotic regimens
      for treatment, its abundance around the world and its vague clinical
      characteristics defying rapid clinical diagnosis are some of the characteristics
      that apply to the pathogen's weapons potential. Yet minimal mortality,
      availability of treatment options, protracted inoculation period and the
      emergence of new, more virulent potential weapons means that its inclusion among
      agents of bioterrorism is nowadays mainly of historical significance.
      Nevertheless, in the interest of literacy and of avoiding panic, physicians and
      the public both should be aware of the most common zoonosis worldwide.

PMID- 16964580
TI  - Development of a matrix to evaluate the threat of biological agents used for
      bioterrorism.
AB  - Adequate public health preparedness for bioterrorism includes the elaboration of
      an agreed list of biological and chemical agents that might be used in an attack
      or as threats of deliberate release. In the absence of counterterrorism
      intelligence information, public health authorities can also base their
      preparedness on the agents for which the national health structures would be most
      vulnerable. This article aims to describe a logical method and the
      characteristics of the variables to be brought in a weighing process to reach a
      priority list for preparedness. The European Union, in the aftermath of the
      anthrax events of October 2001 in the United States, set up a task force of
      experts from multiple member states to elaborate and implement a health security
      programme. One of the first tasks of this task force was to come up with a list
      of priority threats. The model, presented here, allows Web-based updates for
      newly identified agents and for the changes occurring in preventive measures for
      agents already listed. The same model also allows the identification of priority
      protection action areas.

PMID- 16964581
TI  - Hospital preparedness to bioterrorism and other infectious disease emergencies.
AB  - In the last 2 decades, successive outbreaks caused by new, newly recognised and
      resurgent pathogens, and the risk that high-consequence pathogens might be used
      as bioterrorism agents amply demonstrated the need to enhance capacity in
      clinical and public health management of highly infectious diseases. In this
      article we review these recent and current threats to public health, whether
      naturally occurring or caused by accidental or intentional release. Moreover, we
      discuss some components of hospital preparedness for, and response to, infectious
      disease of the emergencies in developed countries. The issues of clinical
      awareness and education, initial investigation and management, surge capacity,
      communication, and caring for staff and others affected by the emergency are
      discussed. We also emphasise the importance of improving the everyday practice of
      infection control by healthcare professionals.

PMID- 16964582
TI  - Bioterrorism: management of major biological agents.
AB  - Bioterrorism is defined by the intentional or threatened of microorganisms or
      toxins derived from living organisms to cause death or diseases in humans,
      animals or plants on which we depend. The other major point is to generate fear
      in the population. More than 180 pathogens have been reported to be potential
      agents for bioterrorism. The following is an overview of several agents that
      could be involved in a biological attack.

PMID- 16964585
TI  - The effects of diazinon on lipid peroxidation and antioxidant enzymes in rat
      heart and ameliorating role of vitamin E and vitamin C.
AB  - Diazinon is one of the most widely used organophosphate insecticides (OPIs) in
      agriculture and public health programs. Reactive oxygen species (ROS) caused by
      OPIs may be involved in the toxicity of various pesticides. The aim of this study
      was to investigate how diazinon affects lipid peroxidation (LPO) and the
      antioxidant defense system in vivo and the possible ameliorating role of vitamins
      E and C. For this purpose, experiments were done to study the effects of DI on
      LPO and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH
      Px), and catalase (CAT) in adult rat heart. Experimental groups were: (1) control
      group, (2) diazinon treated (DI) group, (3) DI+vitamins E and C-treated (DI+Vit)
      group. The levels of malondialdehyde (MDA) and the activities of SOD and CAT
      increased significantly in the DI group compared with the control group. The
      activity of SOD and the levels of MDA decreased significantly in the DI+Vit group
      compared with the DI group. The differences between the DI+Vit and control groups
      according to the MDA levels and the activities of both SOD and CAT were
      statistically significant. These results suggest that treating rats with a single
      dose of diazinon increases LPO and some antioxidant enzyme activities in the rat
      myocardium and, in addition, that single-dose treatment with a combination of
      vitamins E and C after the administration of diazinon can reduce LPO caused by
      diazinon, though this treatment was not sufficiently effective to reduce the
      values to those in control group.

PMID- 16964586
TI  - Expression and transcriptional activities of nuclear receptors involved in
      regulation of drug-metabolizing enzymes are not altered by colchicine: focus on
      PXR, CAR, and GR in primary human hepatocytes.
AB  - Recent findings show that colchicine (COL) in submicromolar concentrations
      downregulates the expression of major drug-metabolizing P450 enzymes in human
      hepatocytes. Concomitantly, the expression of pregnane X receptor (PXR) and
      constitutive androstane receptor (CAR) was diminished by COL, whereas expression
      of glucocorticoid receptor (GR) remained unaltered. A tentative mechanism is
      perturbation of the GR-PXR/CAR-CYP2/3 signaling cascade, resulting in restricted
      transcriptional activity of GR receptor by colchicine. In this work we focused on
      10-demethylcolchicine (colchiceine; EIN), a structural analogue and a putative
      metabolite of COL that lacks tubulin-binding activity. We investigated the
      effects of EIN on the expression of PXR, CAR, and GR receptors in primary
      cultures of human hepatocytes. In contrast with the effects of COL, EIN does not
      alter the expression of PXR, CAR, and/or GR receptors mRNAs. In addition, EIN had
      no effects on transcriptional activities of PXR, CAR, and GR receptors in
      reporter gene assays using transfected cell lines. Considering that COL and EIN
      are structurally very close and differ only in their tubulin-binding activity,
      the data presented imply that the deleterious effects of COL on the GR-PXR/CAR
      CYP2/3 cascade are primarily due to perturbation of the microtubule network. Our
      data support the idea of replacing COL by EIN, which is less toxic and does not
      interact with xenoreceptors.

PMID- 16964587
TI  - Antioxidants and metallothionein levels in mercury-treated mice.
AB  - Acute effects of mercury on mouse blood, kidneys, and liver were evaluated. Mice
      received a single dose of mercuric chloride (HgCl2, 4.6 mg/kg, subcutaneously)
      for three consecutive days. We investigated the possible beneficial effects of
      antioxidant therapy (N-acetylcysteine (NAC) and diphenyl diselenide (PhSe)2)
      compared with the sodium salt of 2,3-dimercapto-1-propanesulfonic acid (DMPS), an
      effective chelating agent in HgCl2 exposure in mice. We also verified whether
      metallothionein (MT) induction might be involved in a possible mechanism of
      protection against HgCl2 poisoning and whether different treatments would modify
      MT levels and other toxicological parameters. The results demonstrated that HgCl2
      exposure significantly inhibited delta-aminolevulinate dehydratase (delta-ALA-D)
      activity in liver and only DMPS treatment prevented the inhibitory effect.
      Mercuric chloride caused an increase in renal non-protein thiol groups (NPSH) and
      none of the treatments modified renal NPSH levels. Urea concentration was
      increased after HgCl2 exposure. NAC plus (PhSe)2 was partially effective in
      protecting against the effects of mercury. DMPS and (PhSe)2 were effective in
      restoring the increment in urea concentration caused by mercury. Thiobarbituric
      acid-reactive substances (TBARS), aspartate aminotransferase (AST), and alanine
      aminotransferase (ALT) activities and ascorbic acid levels were not modified
      after mercury exposure. Mercuric chloride poisoning caused an increase in hepatic
      and renal MT levels and antioxidant treatments did not modify this parameter. Our
      data indicated a lack of therapeutic effect of the antioxidants tested.

PMID- 16964588
TI  - The effect of chelerythrine on cell growth, apoptosis, and cell cycle in human
      normal and cancer cells in comparison with sanguinarine.
AB  - We compared the effects of chelerythrine (CHE) and sanguinarine (SA) on human
      prostate cancer cell lines (LNCaP and DU-145) and primary culture of human
      gingival fibroblasts. CHE and SA treatment of cell lines for 24 h resulted in (1)
      inhibition of cell viability in a dose-dependent manner in all tested cells (as
      evaluated by MTT test and bromodeoxyuridine incorporation assay); (2) dose
      dependent increase in DNA damage in all tested cells (as evaluated by DNA comet
      assay); (3) changes in apoptosis (assessed by western blot analysis and TUNEL
      assay); and (4) significant induction of cyclin kinase inhibitors p21(Waf1/Cip1)
      and p27(Kip1) in prostate cancer cells (identified by western blot analysis). Our
      study demonstrates that CHE had significant cytotoxic effect, independent of p53
      and androgen status, on human prostate cancer cell lines. Normal gingival
      fibroblasts and DU-145 cells were more sensitive to the treatment with both
      alkaloids than were LNCaP cells. CHE and SA may be prospective natural molecules
      for use in the treatment of prostate cancer owing to their involvement in
      apoptosis and cell cycle regulation.

PMID- 16964589
TI  - The role of (18)F-FDG-PET imaging for the selection of liver transplantation
      candidates among hepatocellular carcinoma patients.
AB  - Positron emission tomography (PET) using F-18 fluoro-2-deoxy-d-glucose ((18)F
      FDG) is now well established as a noninvasive diagnostic tool for the detection
      of a variety of malignant tumors. However, in the case of hepatocellular
      carcinoma (HCC), several investigators have reported controversial conclusions
      and an inadequate sensitivity for PET (50-55%). Nevertheless, a high positive
      rate of (18)F-FDG accumulation has been reported in patients with high-grade HCC
      and in those with markedly elevated alpha-fetoprotein (AFP) levels. Here, we
      retrospectively reviewed 38 HCC cases that received liver transplantation (LT) at
      our center between November 2000 and July 2004 and underwent whole-body PET
      imaging. (18)F-FDG uptake was assessed in the liver, and its prognostic
      significance was investigated. Of 38 patients enrolled, 13 patients had positive
      PET scans for a liver tumor. When we analyzed the association between tumor
      factors and PET+ (greater PET lesion uptake) in the liver, preoperative AFP level
      and vascular invasion were found to be significantly associated with PET+ (P =
      0.003 and P < 0.001, respectively). However, the association between histological
      grade and PET+ findings did not reach statistical significant difference (P =
      0.074). Moreover, the 2-year recurrence-free survival rate of PET- patients was
      significantly higher than that of PET+ patients (85.1% vs. 46.1%) (P = 0.0005).
      Of 6 PET+ patients who met the Milan criteria, 4 patients (66.7%) had recurrence,
      but all 20 PET- patients who met the Milan criteria were recurrence free. Thus,
      PET imaging could be a good preoperative tool for estimating the post-LT risk of
      tumor recurrence, because histological grade and vascular invasion cannot be
      determined preoperatively. Importantly, our results indicate that tumor
      recurrence can be highly anticipated for PET-imaging-positive HCC patients who
      satisfy the Milan criteria. We advise that PET+ HCC patients be selected
      cautiously for LT.

PMID- 16964590
TI  - Impact of UCSF criteria according to pre- and post-OLT tumor features: analysis
      of 479 patients listed for HCC with a short waiting time.
AB  - Orthotopic liver transplantation (OLT) indication for hepatocellular carcinoma
      (HCC) is currently based on the Milan criteria. The University of California, San
      Francisco (UCSF) recently proposed an expansion of the selection criteria
      according to tumors characteristics on the explanted liver. This study: 1)
      assessed the validity of these criteria in an independent large series and 2)
      tested for the usefulness of these criteria when applied to pre-OLT tumor
      evaluation. Between 1985 and 1998, 479 patients were listed for liver
      transplantation (LT) for HCC and 467 were transplanted. According to pre-OLT
      (imaging at date of listing) or post-OLT (explanted liver) tumor characteristics,
      patients were retrospectively classified according to both the Milan and UCSF
      criteria. The 5-yr survival statistics were assessed by the Kaplan-Meier method
      and compared by the log-rank test. Pre-OLT UCSF criteria were analyzed according
      to an intention-to-treat principle. Based on the pre-OLT evaluation, 279 patients
      were Milan+, 44 patients were UCSF+ but Milan- (subgroup of patients that might
      benefit from the expansion), and 145 patients were UCSF- and Milan-. With a short
      median waiting time of 4 months, 5-yr survival was 60.1 +/- 3.0%, 45.6 +/- 7.8%,
      and 34.7 +/- 4.0%, respectively (P < 0.001). The 5-yr survival was arithmetically
      lower in UCSF+ Milan- patients compared to Milan+ but this difference was not
      significant (P = 0.10). Based on pathological features of the explanted liver, 5
      yr survival was 70.4 +/- 3.4%, 63.6 +/- 7.8%, and 34.1 +/- 3.1%, in Milan+
      patients (n = 184), UCSF+ Milan- patients (n = 39), and UCSF- Milan- patients (n
      = 238), respectively (P < 0.001). However, the 5-yr survival did not differ
      between Milan+ and UCSF+ Milan- patients (P = 0.33). In conclusion, these results
      show that when applied to pre-OLT evaluation, the UCSF criteria are associated
      with a 5-yr survival below 50%. Their applicability is therefore limited, despite
      similar survival rates compared to the Milan criteria, when the explanted liver
      is taken into account.

PMID- 16964591
TI  - Activation-induced cytidine deaminase: structure-function relationship as based
      on the study of mutants.
AB  - Activation-induced cytidine deaminase (AID; gene symbol AICDA) is the key
      molecule required to induce immunoglobulin (Ig) class switch recombination (CSR)
      and somatic hypermutation (SHM) of the variable regions of Ig genes. Its
      deficiency causes a form of hyper-IgM (HIGM) syndrome. The study of natural AID
      mutants associated with HIGM as well as engineered mutants led to the
      characterization of the active domains of the protein. AID, through its cytidine
      deaminase activity, induces a targeted DNA lesion as an early step required for
      both CSR and SHM. Besides its cytidine deaminase activity, AID plays a further
      essential role in CSR, likely by recruiting CSR-specific cofactors by its C
      terminus. A similar binding of SHM-specific cofactors to the N-terminal part is
      suggested by the functional characteristics of N(ter) AID artificial mutants.
      These data require confirmation in vivo. Finally, AID acts as a homo-, di-, or
      multimeric complex. Together, these data strongly suggest that AID, a master
      molecule for antibody diversification, exerts its activity on CSR not only as a
      cytidine deaminase enzyme but also as a docking protein, recruiting specific
      cofactors to a multimeric complex.

PMID- 16964592
TI  - The role of altered acetyl-CoA carboxylase in conferring resistance to fenoxaprop
      P-ethyl in Chinese sprangletop (Leptochloa chinensis (L.) Nees).
AB  - From paddy field observations in 2002 and 2004, fenoxaprop-P-ethyl resistance in
      Chinese sprangletop (Leptochloa chinensis (L.) Nees) has been studied using
      information collected from 11 sites in the Saphan-Sung district of Bangkok,
      Thailand. The resistant Chinese sprangletop was found in nine rice fields,
      whereas the susceptible Chinese sprangletop was found in only two rice fields. In
      greenhouse experiments, both fenoxaprop-P-ethyl-resistant and susceptible Chinese
      sprangletop from the same location were investigated for 50% growth reduction
      based on phytotoxicity, plant height and fresh and dry weight. The resistant
      Chinese sprangletop showed apparent resistance at 14-21 days after herbicide
      application at a rate of 21.1-337.6 g AI ha(-1). The resistance index of
      resistant Chinese sprangletop was 10-25 times higher than that of the susceptible
      Chinese sprangletop. In addition, Chinese sprangletop did not exhibit multiple
      resistance to oxadiazon, propanil and quinclorac. According to acetyl-CoA
      carboxylase (ACCase) assays, the level of ACCase specific activity in the
      resistant Chinese sprangletop was significantly higher than that in the
      susceptible Chinese sprangletop. Similarly, the ACCase activity of the resistant
      Chinese sprangletop was 10 times less sensitive to fenoxaprop-P-ethyl than that
      of the susceptible Chinese sprangletop, based on the I50 values. The present
      study of the mechanism responsible for resistance in the biotypes investigated
      indicated that there was a close association between the concentration-response
      at the whole-plant level and ACCase sensitivity to fenoxaprop-P-ethyl, and
      resistance to fenoxaprop-P-ethyl was conferred by a modified ACCase at the target
      site, as suggested by higher specific activity and less sensitivity to the
      herbicide.

PMID- 16964593
TI  - Weak definition of IKBKAP exon 20 leads to aberrant splicing in familial
      dysautonomia.
AB  - Splicing mutations that lead to devastating genetic diseases are often located in
      nonconserved or weakly conserved sequences that normally do not affect splicing.
      Thus, the underlying reason for the splicing defect is not immediately obvious.
      An example of this phenomenon is observed in the neurodevelopmental disease
      familial dysautonomia (FD), which is caused by a single-base change in the 5'
      splice site (5'ss) of intron 20 in the IKBKAP gene (c.2204+6T>C). This mutation,
      which is in the sixth position of the intron and results in exon 20 skipping, has
      no phenotype in many other introns. To determine why the position 6 mutation
      causes aberrant splicing only in certain cases, we first used an in silico
      approach to identify potential sequences involved in exon 20 skipping.
      Computational analyses of the exon 20 5'ss itself predicted that this nine
      nucleotide splicing signal, even when it contains the T>C mutation, is not
      sufficiently weak to explain the FD phenotype. However, the computational
      analysis predicted that both the upstream 3' splice site (3'ss) and exon 20
      contain weak splicing signals, indicating that the FD 5'ss, together with the
      surrounding splicing signals, are not adequate for defining exon 20. These in
      silico predictions were corroborated using IKBKAP minigenes in a new rapid and
      simple in vitro coupled RNA polymerase (RNAP) II transcription/splicing assay.
      Finally, the weak splicing signals that flank the T>C mutation were validated as
      the underlying cause of familial dysautonomia in vivo using transient
      transfection assays. Together, our study demonstrates the general utility of
      combining in silico data with an in vitro RNAP II transcription/splicing system
      for rapidly identifying critical sequences that underlie the numerous splicing
      diseases caused by otherwise silent mutations.

PMID- 16964594
TI  - Impact of human leukocyte antigen mismatching on outcomes of living donor liver
      transplantation for primary biliary cirrhosis.
AB  - Patient selection criteria of deceased donor liver transplantation for primary
      biliary cirrhosis (PBC) are almost completely established. The aim of this study
      was to establish selection criteria for both patients and donors of living donor
      liver transplantation (LDLT) for PBC. We used univariate and multivariate
      analyses to examine patient and donor characteristics of our first 50 cases of
      LDLT for PBC to elucidate factors that significantly impacted patient survival or
      disease recurrence after LDLT in the univariate and/or multivariate analyses.
      Multivariate analysis demonstrated that the presence of persistent ascites before
      LDLT, a higher number of human leukocyte antigen (HLA)-A, -B, and -DR mismatches
      between donor and recipient, and donor age >or=50 years were factors
      significantly associated with early posttransplant death. Independent risk
      factors for PBC recurrence after LDLT were a lower number of HLA mismatches
      between donor and recipient, and a lower average trough level of tacrolimus
      within 1 year after LDLT. Specifically, the lower the number of HLA-A, -B, and 
      DR mismatches or the average trough level of tacrolimus within 1 year after LDLT,
      the higher the possibility of developing a recurrence of PBC. In conclusion, the
      absence of persistent ascites before LDLT, a lower number of HLA-A, -B, and -DR
      mismatches between donor and recipient, and a younger donor (<50 years) are
      preferred for gaining acceptable survival outcomes for the transplant. However, a
      lower number of HLA-A, -B, and -DR mismatches between donor and recipient may be
      a risk factor for PBC recurrence.

PMID- 16964595
TI  - Immunogenicity and safety of an experimental adjuvanted hepatitis B candidate
      vaccine in liver transplant patients.
AB  - Patients with chronic liver disease are at higher risk of hepatitis B (HB) virus
      infection before and after liver transplantation, and they commonly have a
      suboptimal immune response to HB vaccines. In this randomized trial, we compared
      the immunogenicity of primary vaccination with 2 doses of an experimental
      adjuvanted HB vaccine (adjuvant system 04 containing aluminium and monophosphoryl
      lipid A [HB-AS04]) to that of 3 double doses of a licensed HB vaccine in 93 liver
      transplant candidates. Depending on the waiting list for liver transplantation, a
      booster dose of HB-AS04 or double booster dose of the licensed HB vaccine was
      given before or after surgery, at 6 to 12 months after initiation of the
      vaccination course. The percentage of subjects with seroprotective anti-HB
      surface antibody concentrations 1 month after booster was twice as high in the HB
      AS04 group (60.0%), vs. patients in the comparator group (32.0%) (P = 0.035). In
      subjects who did not undergo liver transplantation before administration of the
      booster, better immunogenicity results were obtained: 80% of subjects were
      seroprotected after HB-AS04 vaccination vs. 60% with the comparator (P = 0.2302).
      Despite a slightly higher reactogenicity, the safety profile of the HB-AS04
      vaccine was clinically acceptable. In conclusion, an improved antibody response
      was observed in liver transplant candidates with 3 doses of HB-AS04, as compared
      to 4 double doses of a comparator. Liver transplant candidates could benefit from
      the use of this experimental adjuvanted HB vaccine to further increase their
      protection against HB infection.

PMID- 16964596
TI  - Inheritance of sutural pattern at the pterion in Rhesus monkey skulls.
AB  - Five of the bones that characteristically comprise the cranial vault articulate
      on the lateral aspect of the skull at or near the cephalometric landmark referred
      to as the pterion. The pattern of articulation in the sutures associated with
      these bones varies among and within primate species and has been used as a
      criterion for classification in taxonomic studies, as well as in archeological
      and forensic studies. Within species, the sutural patterns found within the
      region of the pterion have remarkable consistency, which lead to the hypothesis
      that these patterns have a genetic basis. Sutural pattern variations were
      investigated at the pterion in 422 skulls from 66 rhesus monkey families with
      known genealogies from the long-standing colony on Cayo Santiago. Four specific
      types of articulation patterns were recorded. The results demonstrated that the
      most common suture pattern at the pterion of Cayo Santiago rhesus monkeys (86%;
      similar to that seen in some other anthropoid species but not humans and some
      apes) was characterized by an articulation between the temporal bone and parietal
      bone. Articulation between the sphenoid and parietal bones (type SP) accounted
      for 14% of the specimens and was concentrated in a dozen families. Mothers with
      the SP phenotype had a high incidence of offspring with SP phenotypes. Most non
      SP mothers having SP offspring had siblings or family members from previous
      generations with the SP type. This is the first study to examine variation in
      sutural patterns at the pterion in pedigrees. Variation of sutural patterns shows
      familial aggregation, suggesting that this variation is heritable. Future work
      will be focused on defining the inheritance patterns of variation at the pterion,
      with the ultimate objective of identifying the specific genes involved and their
      mechanism of action.

PMID- 16964597
TI  - Impact of donor age on survival and fibrosis progression in patients with
      hepatitis C undergoing liver transplantation using HCV+ allografts.
AB  - Studies have suggested that the use of hepatitis C virus (HCV)-positive (HCV+)
      donor allografts has no impact on survival. However, no studies have examined the
      effect that HCV+ donor histology has upon recipient and graft survival. We
      evaluated the clinical outcome and impact of histological features in HCV
      patients transplanted using HCV+ livers. We reviewed all patients transplanted
      for HCV at our institution from 1988 to 2004; 39 received HCV+ allografts and 580
      received HCV-negative (HCV-) allografts. Survival curves compared graft and
      patient survival. Each HCV+ allograft was stringently matched to a control of HCV
      graft recipients. No significant difference in survival was noted between
      recipients of HCV+ livers and controls. Patients receiving HCV+ allografts from
      older donors (age > or =50 yr) had higher rates of graft failure (hazard ratio,
      2.74) and death rates (hazard ratio, 2.63) compared to HCV- allograft recipients
      receiving similarly-aged older donor livers. Matched case-control analysis
      revealed that recipients of HCV+ allografts had more severe fibrosis post-liver
      transplantation than recipients of HCV- livers (P = 0.008). More advanced
      fibrosis was observed in HCV+ grafts from older donors compared to HCV+ grafts
      from younger donors (P = 0.012). In conclusion, recipients of HCV+ grafts from
      older donors have higher rates of death and graft failure, and develop more
      extensive fibrosis than HCV- graft recipients from older donors. Recipients of
      HCV+ grafts, regardless of donor age, develop more advanced liver fibrosis than
      recipients of HCV- grafts.

PMID- 16964598
TI  - Age and gender dependence of human cardiac phosphorus metabolites determined by
      SLOOP 31P MR spectroscopy.
AB  - The aim of this study was to apply (31)P magnetic resonance spectroscopy (MRS)
      using spatial localization with optimal point spread function (SLOOP) to
      investigate possible age and gender dependencies of the energy metabolite
      concentrations in the human heart. Thirty healthy volunteers (18 males and 12
      females, 21-67 years old, mean = 40.7 years) were examined with the use of (31)P
      MRS on a 1.5 T scanner. Intra- and interobserver variability measures (determined
      in eight of the volunteers) were both 3.8% for phosphocreatine (PCr), and 4.7%
      and 8.3%, respectively, for adenosine triphosphate (ATP). High-energy phosphate
      (HEP) concentrations in mmol/kg wet weight were 9.7 +/- 2.4 (age < 40 years, N =
      16) and 7.7 +/- 2.5 (age >or= 40 years, N = 14) for PCr, and 5.1 +/- 1.0 (age <
      40 years) and 4.1 +/- 0.8 (age >or= 40 years) for ATP, respectively. Separated by
      gender, PCr concentrations of 9.2 +/- 2.4 (men, N = 18) and 8.0 +/- 2.8 (women, N
      = 12) and ATP concentrations of 4.9 +/- 1.0 (men) and 4.2 +/- 0.9 (women) were
      measured. A significant decrease of PCr and ATP was found for volunteers older
      than 40 years (P < 0.05), but the differences in metabolic concentrations between
      both sexes were not significant. In conclusion, age has a minor but still
      significant impact on cardiac energy metabolism, and no significant gender
      differences were detected.

PMID- 16964599
TI  - pH-dependent aggregation of cutinase is efficiently suppressed by 1,8-ANS.
AB  - We have studied the thermal stability of the triglyceride-hydrolyzing enzyme
      cutinase from F. solani pisi at pH values straddling the pI (pH 8.0). At the pI,
      increasing the protein concentration from 5 to 80 microM decreases the apparent
      melting temperature by 19 degrees C. This effect vanishes at pH values more than
      one unit away from pI. In contrast to additives such as detergents and osmolytes,
      the hydrophobic fluorophore 1,8-ANS completely and saturably suppresses this
      effect, restoring 70% of enzymatic activity upon cooling. ANS binds strongly to
      native cutinase as a noncompetitive inhibitor with up to 5 ANS per cutinase
      molecule. Only the first ANS molecule stabilizes cutinase; however, the last 4
      ANS molecules decrease Tm by up to 7 degrees C. Similar pI-dependent aggregation
      and suppression by ANS is observed for T. lanuginosus lipase, but not for
      lysozyme or porcine alpha-amylase, suggesting that this behavior is most
      prevalent for proteins with affinity for hydrophobic substrates and consequent
      exposure of hydrophobic patches. Aggregation may be promoted by a fluctuating
      ensemble of native-like states associating via intermolecular beta-sheet rich
      structures unless blocked by ANS. Our data highlight the chaperone activity of
      small molecules with affinity for hydrophobic surfaces and their potential
      application as stabilizers at appropriate stoichiometries.

PMID- 16964600
TI  - Nonisothermal denaturation kinetics of human hair and the effects of oxidation.
AB  - Human hair as alpha-keratin fiber exhibits a complex morphology, which for the
      context of this investigation is considered as a filament/matrix-composite,
      comprising the intermediate filaments (IF) and a variety of amorphous protein
      components as matrix. Differential scanning calorimetry (DSC) under aqueous
      conditions was used to analyze the denaturation of the alpha-helical material in
      the IFs and to assess the changes imparted by repeated, oxidative bleaching
      processes. The DSC curves were submitted to kinetic analysis by applying the
      Friedman method and assuming first order kinetics. It was found that the course
      of the denaturation process remains largely unchanged through oxidation, despite
      the fact that pronounced decreases of denaturation temperature as well as of
      enthalpy occur. In parallel, the reaction rate constant at the denaturation
      temperature, k(TD), increases with repeated treatments, that is with cumulative
      chemical modification. However, this effect is in fact small compared to the
      overall change of k(T) through the denaturation process. This leads to conclude
      that once the temperature rise in combination with the chemical change has
      induced a suitable drop of the viscosity of the matrix around the IFs,
      denaturation of the remaining helical material occurs along a pathway that is
      largely independent of temperature and of the pretreatment history. This
      emphasizes the kinetic control of the matrix over the denaturation process of the
      helical segments in the filament/matrix composite.

PMID- 16964601
TI  - All-atom contact potential approach to protein thermostability analysis.
AB  - In this paper we use all-atom potential energy to define and analyze the inter
      residue contacts in mesophilic and thermophilic proteins. Fifteen families of
      proteins are selected and each family has two representative proteins with
      greatly different preferred environmental temperatures. We find that both the
      number and energy of the contacts defined in this way show stronger correlations
      with the preferred temperatures of proteins than other factors used before. We
      also find that the charged-polar and charged-nonpolar residue contacts not only
      have larger contact numbers but also have lower single contact energies.
      Furthermore, the most important is that most of the thermophilic proteins have
      more charged-polar and charged-nonpolar residue contacts than their mesophilic
      counterparts. This suggests that they may play an important role in the
      thermostability of proteins, except usual charged-charged and nonpolar-nonpolar
      residue contacts. Charged residues may exert their profound influence by forming
      contacts not only with other charged residues but also with polar or nonpolar
      residues, thus further increasing the strength of contact network and then the
      thermostability of proteins.

PMID- 16964602
TI  - Pulsed magnetization transfer imaging with body coil transmission at 3 Tesla:
      feasibility and application.
AB  - Pulsed magnetization transfer (MT) imaging has been applied to quantitatively
      assess brain pathology in several diseases, especially multiple sclerosis (MS).
      To date, however, because of the high power deposition associated with the use of
      short, rapidly repeating MT prepulses, clinical application has been limited to
      lower field strengths. The contrast-to-noise ratio (CNR) of MT is limited, and
      this method would greatly benefit from the use of higher magnetic fields and
      phased-array coil reception. However, power deposition is proportional to the
      square of the magnetic field and scales with coil size, and MT experiments are
      already close to the SAR limit at 1.5T even when smaller transmit coils are used
      instead of the body coil. Here we show that these seemingly great obstacles can
      be ameliorated by the increased T(1) of tissue water at higher field, which
      allows for longer maintenance of sufficiently high saturation levels while using
      a reduced duty cycle. This enables a fast (5-6 min) high-resolution (1.5 mm
      isotropic) whole-brain MT acquisition with excellent anatomical visualization of
      gray matter (GM) and white matter (WM) structures, and even substructures. The
      method is demonstrated in nine normal volunteers and five patients with relapsing
      remitting MS (RRMS), and the results show a clear delineation of heterogeneous
      lesions.

PMID- 16964603
TI  - Hypothetical anatomical model to describe the aberrant gag reflex observed in a
      clinical population of orally deprived children.
AB  - In this 'clinical conundrum', we propose a hypothetical anatomical model to
      explain the abnormal gag reflex that is consistently observed in a clinical
      population of children experiencing feeding delays. This model is based on the
      presence of 'transient' connections formed during the normal development of
      autonomic brainstem circuitry involving the nucleus tractus solitarius (NTS). We
      propose that, as a result of normal feeding and swallowing, the activity of these
      transient fibers typically diminishes shortly after birth. In children who are
      orally deprived during infancy, these transient connections persist and the
      aberrant gag reflex is maintained into childhood. The most critical feature of
      the proposed model is the idea that swallowing during feeding initiates the
      retraction of the tactile 'transient' input to NTS. In the NICU feeding clinics,
      it has been suggested that triggering the gag reflex in neonates by tactile
      stimulation of non-oral body areas and anterior portions of the mouth directly or
      indirectly may contribute to oral feeding delays. To the contrary, we propose an
      anatomical model to suggest that oral feeding delays and lack of swallowing food,
      when experienced by neonates, actually contribute to the development of the
      aberrant gag reflex observed in later developmental stages.

PMID- 16964604
TI  - Computed axial tomography scanning (CT scan).

PMID- 16964605
TI  - Comment on "a new device for cricothyroidotomy".

PMID- 16964606
TI  - A green to red photoconvertible protein as an analyzing tool for early vertebrate
      development.
AB  - Lineage labeling is one of the most important techniques in developmental
      biology. Most recently, a set of photoactivatable fluorescent proteins
      originating from marine cnidarians became available. Here, we introduce the
      application of the green to red photoconvertible protein EosFP as a novel
      technique to analyze early vertebrate development. Both injection of EosFP mRNA
      and purified, recombinant EosFP followed by a light-driven green to red
      conversion allow lineage labeling in virtually any temporal and spatial dimension
      during embryonic development for at least 2 weeks. Specific staining of cells
      from nonsurface layers is greatly facilitated by light-driven conversion of EosFP
      compared with traditional methods. Therefore, green to red photoactivatable
      proteins promise to be a powerful tool with the potential to satisfy the
      increasing demand for methods enabling detailed phenotypical analyses after
      manipulations of morphogenetic events, gene expression, or signal transduction.

PMID- 16964607
TI  - Chromaffin cells in the adrenal homolog of Aphanius fasciatus (teleost fish)
      express piecemeal degranulation in response to osmotic stress: a hint for a
      conservative evolutionary process.
AB  - The effect of severe osmotic stress on the ultrastructural morphology of
      chromaffin cells in the adrenal homolog of Aphanius fasciatus, a small eurhyaline
      teleost living in saltpans, was evaluated by electron microscopy quantitative
      analysis. Fishes were transferred from salt water, whose salinity was 3.7%, to
      dechlorinated tap water and chromaffin cells were studied at resting condition
      and after 2 and 48 hr from the beginning of the experiment. Ultrastructural
      examination revealed a series of granule and cytoplasmic changes highly specific
      for piecemeal degranulation (PMD), a secretory process based on vesicular
      transport of cargoes from within granules for extracellular release, which was
      previously described in chromaffin cells of the mouse, rat, and human adrenal
      medulla. There was indeed a significant trend toward loss of content material
      from chromaffin granules accompanied by enlargement of granule size. Remarkably,
      chromaffin granules maintained their individual close structure during the whole
      releasing process and eventually transformed into large empty containers. A
      dramatic increase in the density of small, membrane-bound, variably electron
      dense vesicles free in the cytoplasm or attached to granules was recognized
      during the first 2 hr of stress response. These features fell to control levels
      after 48 hr. A similar time-course pattern was observed concerning the formation
      of budding projections from the surface of chromaffin granules. This study
      provides new insight into PMD physiology and suggests that PMD is part of an
      adaptive secretory response to severe osmotic stress in fishes. From an
      evolutionary point of view, this study lends support to the concept that PMD is a
      secretory mechanism highly conserved throughout vertebrate classes.

PMID- 16964608
TI  - Analysis of pancreatic endocrine development in GDF11-deficient mice.
AB  - Here, we examine the role of GDF11 in pancreatic development. Using in situ
      hybridization and reverse transcriptase-polymerase chain reaction analyses, we
      show that Gdf11 transcripts are expressed in embryonic pancreas epithelium before
      the secondary transition but decrease rapidly afterward. To determine the
      function of GDF11 during pancreas development, we analyzed Gdf11(-/-) mouse
      embryos. In such embryos, pancreas size is twofold reduced at embryonic day (E)
      18 compared with wild-type littermates. Quantification of the different tissue
      compartments shows a specific hypoplasia of the exocrine compartment, while the
      endocrine and ductal compartments are unaffected. Notably, NGN3(+) endocrine
      precursor cells are increased fourfold at E18, although the amount of endocrine
      cells in the pancreas of these animals is unchanged compared with wild-type
      littermates. Similarly, the maturation of endocrine cells as well as the ratio
      between alpha- and beta-cells appears normal.

PMID- 16964609
TI  - Cephalic vascular anatomy in flamingos (Phoenicopterus ruber) based on novel
      vascular injection and computed tomographic imaging analyses.
AB  - Head vascular anatomy of the greater (or Caribbean) flamingo (Phoenicopterus
      ruber) is investigated and illustrated through the use of a differential
      contrast, dual vascular injection technique, and high-resolution X-ray computed
      tomography (CT), allowing arteries and veins to be differentiated
      radiographically. Vessels were digitally isolated with segmentation tools and
      reconstructed in 3D to facilitate topographical visualization of the cephalic
      vascular tree. Major vessels of the temporal, orbital, pharyngeal, and encephalic
      regions are described and illustrated, which confirm that the general pattern of
      avian cephalic vasculature is evolutionarily conservative. In addition to
      numerous arteriovenous vascular devices, a previously undescribed, large,
      bilateral, paralingual cavernous sinus that excavates a large bony fossa on the
      medial surface of the mandible was identified. Despite the otherwise conservative
      vascular pattern, this paralingual sinus was found only in species of flamingo
      and is not known otherwise in birds. The paralingual sinus remains functionally
      enigmatic, but a mechanical role in association with the peculiar lingual-pumping
      mode of feeding in flamingos is perhaps the most likely hypothesis.

PMID- 16964610
TI  - Bayesian inference of hemodynamic changes in functional arterial spin labeling
      data.
AB  - The study of brain function using MRI relies on acquisition techniques that are
      sensitive to different aspects of the hemodynamic response contiguous to areas of
      neuronal activity. For this purpose different contrasts such as arterial spin
      labeling (ASL) and blood oxygenation level dependent (BOLD) functional MRI
      techniques have been developed to investigate cerebral blood flow (CBF) and blood
      oxygenation, respectively. Analysis of such data typically proceeds by separate,
      linear modeling of the appropriate CBF or BOLD time courses. In this work an
      approach is developed that provides simultaneous inference on hemodynamic changes
      via a nonlinear physiological model of ASL data acquired at multiple echo times.
      Importantly, this includes a significant contribution by changes in the static
      magnetization, M, to the ASL signal. Inference is carried out in a Bayesian
      framework. This is able to extract, from dual-echo ASL data, probabilistic
      estimates of percentage changes of CBF, R(2) (*), and the static magnetization,
      M. This approach provides increased sensitivity in inferring CBF changes and
      reduced contamination in inferring BOLD changes when compared with general linear
      model approaches on single-echo ASL data. We also consider how the static
      magnetization, M, might be related to changes in CBV by assuming the same
      mechanism for water exchange as in vascular space occupancy.

PMID- 16964611
TI  - Time trends of breast cancer survival in Europe in relation to incidence and
      mortality.
AB  - Increasing breast cancer survival, observed in most western countries, is not
      easily interpreted: it could be due to better treatment, more effective treatment
      due to earlier diagnosis or simply lead-time bias. Increased diagnostic activity
      (e.g., screening) can inflate both incidence and survival. To understand
      interrelations between incidence, mortality and survival trends and their
      consequences, we analyzed survival trends in relation to mortality and incidence.
      Starting with observed survival from EUROCARE, mortality from WHO and using the
      MIAMOD method, we estimated breast cancer incidence trends from 1970 to 2005 in
      10 European countries. To smooth out peaks in incidence and survival due to early
      diagnosis activity, survival trends were assumed similar to those observed by
      EUROCARE in 1983-1994. The following patterns emerged: (1) increasing survival
      with increasing incidence and declining or stable mortality (Sweden, Finland);
      (2) slight survival increase, marked incidence increase and slight mortality
      decrease (Denmark, the Netherlands and France); (3) increasing survival, marked
      decrease in mortality and tendency to incidence stabilization (UK); (4) marked
      survival increase, steady or decreasing mortality and moderate increases in
      incidence (Spain, Italy); (5) stable survival, increasing incidence and mortality
      (Estonia). In most countries survival increased, indicating a real advantage for
      patients when accompanied by decreasing or stable mortality, and attributable to
      improved cancer care (Sweden, UK, France, Italy and Spain). In Finland (with high
      survival), the Netherlands and Denmark, increasing mortality and incidence
      indicate increasing breast cancer risk, probably related to life-style factors.
      In Estonia, low and stable survival in the context of increasing incidence and
      mortality suggests inadequate care.

PMID- 16964612
TI  - On restoring motion-induced signal loss in single-voxel magnetic resonance
      spectra.
AB  - Destructive interference from phase fluctuations caused by motion during (1)H
      magnetic resonance spectroscopy (MRS) stimulated-echo acquisition mode (STEAM)
      and point-resolved spectroscopy (PRESS) acquisitions can significantly diminish
      the traditional radicalN-gain in signal-to-noise ratio (SNR) afforded by
      averaging N signals, especially in the torso. The SNR loss is highly variable
      among individuals, even when identical acquisition protocols are used. This paper
      presents a theory for the SNR loss, assuming that the phase fluctuates randomly.
      It is shown that SNR in conventional averaging is reduced by the factor
      sinc(sigma(phi) radical3/pi), where sigma(phi) is the standard deviation (SD) of
      the phase. "Constructive averaging," whereby each individual acquisition is phase
      corrected using the phase of a high-SNR peak before averaging, reverses the SNR
      loss from motion-induced dephasing, resulting in a {1/sinc(sigma(phi)
      radical3/pi)}-fold SNR improvement. It is also shown that basing phase
      corrections on an average of radicalN adjacent points both improves correction
      accuracy and effectively eliminates false signal artifacts when corrections are
      based on low-SNR peaks. The theory is validated over a sevenfold range of
      variation in signal loss due to motion observed in (1)H STEAM and PRESS data
      acquired from 17 human subjects (heart: N = 16; leg: N = 1). Constructive
      averaging should be incorporated as a routine tool for in vivo (1)H MRS.

PMID- 16964613
TI  - Spatially resolved time-course studies of free radical reactions with an EPRI/MRI
      fusion technique.
AB  - Electron paramagnetic resonance imaging (EPRI) using nitroxyl radicals is a
      useful technique for visualizing reactive oxygen species (ROS) and the
      pharmacokinetics of probes. To unambiguously identify anatomical locations,
      coregistration of EPRI with images obtained by MRI is necessary. In this study
      the feasibility of performing reliable EPRI/MRI fusion imaging using nitroxyl
      radical fiducial markers was tested. The pharmacokinetics of the nitroxyl
      radicals were observed after oral or intravenous administration in C57BL6 mice.
      To fuse both images, the nitroxyl radical was used as fiducial markers. The EPR
      and MR images corresponded well and clearly illustrated minimal changes in
      pharmacokinetics between carbamoyl-PROXYL and carboxy-PROXYL. These results
      demonstrate that the EPRI/MRI fused imaging technique is useful for investigating
      in vivo pharmacokinetics and provides unambiguous anatomic details.

PMID- 16964614
TI  - Optimized detection of lactate at high fields using inner volume saturation.
AB  - In localized proton MR spectroscopy ((1)H-MRS) in vivo, the detection of lactate
      (Lac) is affected by modulation of its resonances due to homonuclear scalar
      couplings (J). A simple and convenient way to distinguish Lac from lipids is to
      set the TE to 1/J so that the Lac signal is inverted while other resonances (such
      as lipid) remain in-phase. However, at high field strengths, such as 3 Tesla or
      above, the modulation of the Lac signal is complicated by chemical shift effects
      that cause modulation patterns to vary within different subregions of the
      localized volume. Under some conditions the Lac signal may even disappear
      completely. In this note we introduce the concept of inner volume saturation
      (IVS), which makes use of high bandwidth spatial pulses to remove the signal
      corresponding to the regions of the localized volume that contribute unwanted
      modulation patterns. The method is described theoretically and demonstrated
      experimentally at 3 Tesla in a phantom and a patient with acute stroke. The
      phantom measurements indicate that virtually 100% of the Lac signal can be
      recovered using this method. The method should be feasible at magnetic fields
      above 3 Tesla, and may also be applied to other coupled spin systems in which
      modulation effects are important.

PMID- 16964615
TI  - High-resolution continuously acquired peripheral MR angiography featuring partial
      parallel imaging GRAPPA.
AB  - Continuously-moving-table MRI, in contrast to traditional multistation
      techniques, potentially can improve the scan time efficiency of whole-body
      applications and provide seamless images of an extended field of view (FOV).
      Contrast-enhanced MR angiography (CE-MRA) in particular requires high spatial
      resolution and at the same time has rigid scan time constraints due to the
      limited arterial contrast window. In this study a reconstruction method for
      continuously acquired 3D data sets during table movement was combined with a self
      calibrated partial parallel imaging algorithm (generalized autocalibrating
      partially parallel acquisitions (GRAPPA)). The method was applied to peripheral
      CE-MRA and compared with a standard continuously-moving-table MRA protocol. The
      gain in scan time was used to increase the data acquisition matrix and decrease
      the slice thickness. The method was evaluated in five healthy volunteers and
      applied to one patient with peripheral arterial occlusive disease (PAOD). The
      protocols were intraindividually compared with respect to the signal-to-noise
      ratio (SNR) and contrast-to-noise ratio (CNR) in selected vessel segments, as
      well as overall vessel depiction. The combination of the continuously-moving
      table technique with parallel imaging enabled the acquisition of seamless
      peripheral 3D MRA with increased resolution and an overall crisper appearance.

PMID- 16964616
TI  - Dynamic magnetic resonance inverse imaging of human brain function.
AB  - MRI is widely used for noninvasive hemodynamic-based functional brain imaging. In
      traditional spatial encoding, however, gradient switching limits the temporal
      resolution, which makes it difficult to unambiguously identify possible fast
      nonhemodynamic changes. In this paper we propose a novel reconstruction approach,
      called dynamic inverse imaging (InI), that is capable of providing millisecond
      temporal resolution when highly parallel detection is used. To achieve an order
      of-magnitude speedup in generating time-resolved contrast estimates and dynamic
      statistical parametric maps (dSPMs), the spatial information is derived from an
      array of detectors rather than by time-consuming gradient-encoding methods. The
      InI approach was inspired by electroencephalography (EEG) and
      magnetoencephalography (MEG) source localization techniques. Dynamic MR InI was
      evaluated by means of numerical simulations. InI was also applied to measure BOLD
      hemodynamic time curves at 20-ms temporal resolution in a visual stimulation
      experiment using a 90-channel head array. InI is expected to improve the time
      resolution of MRI and provide increased flexibility in the trade-off between
      spatial and temporal resolution for studies of dynamic activation patterns in the
      human brain.

PMID- 16964617
TI  - Assessment of normal fetal brain maturation in utero by proton magnetic resonance
      spectroscopy.
AB  - Cerebral maturation in the normal human fetal brain was investigated by in utero
      localized proton MR spectroscopy ((1)H MRS). Fifty-eight subjects at 22-39 weeks
      of gestational age (GA) were explored. A combination of anterior body phased
      array coils (four elements) and posterior spinal coils (two to three elements)
      was used. Four sequences were performed (point-resolved spectroscopy (PRESS)
      sequence with short and long TEs (30 and 135 ms), with and without water
      saturation). A significant reduction in myo-inositol (myo-Ins) and choline (Cho)
      levels, and an increase in N-acetylaspartate (NAA) and creatine (Cr) content were
      observed with progressing age. A new finding is the detection of NAA as early as
      22 weeks of GA. This result is probably related to the fact that oligodendrocytes
      (whether mature or not) express NAA, as demonstrated by in vitro studies. Cho and
      myo-inositol were the predominant resonances from 22 to 30 weeks and decreased
      gradually, probably reflecting the variations in substrate needed for membrane
      synthesis and myelination. The normal MRS data for the second trimester of
      gestation (when fetal MRI is usually performed) reported here can help determine
      whether brain metabolism is altered or not, especially when subtle anatomic
      changes are observed on conventional images.

PMID- 16964618
TI  - Enhanced T2 contrast for MR histology of the mouse brain.
AB  - A 3D Carr-Purcell-Meiboom-Gill (CPMG) sequence was implemented to obtain enhanced
      T(2) contrast in actively stained (perfusion with fixative and contrast agent)
      mouse brains at 9.4 T. Short interecho spacing was used to minimize diffusion and
      susceptibility losses. The sequence produced 16 3D volumes with an interecho
      spacing of 7 ms for isotropic 43-mu-resolution images of the mouse brains in a
      scan time of 4 hr. To enhance the signal-to-noise ratio (SNR) and contrast, the
      multiecho frequency domain image contrast (MEFIC) method was applied, resulting
      in a composite image with T(2)-weighted contrast. The high SNR and contrast thus
      achieved revealed aspects of mouse brain morphology, such as multiple cortical
      layers, groups of thalamic nuclei, layers of the inferior and superior
      colliculus, and molecular and granular layers of the cerebellum, with a high
      degree of definition and contrast that was not previously achieved in T(2)
      weighted acquisitions at high fields.

PMID- 16964619
TI  - Significance of case reports in the advancement of medical scientific knowledge.
AB  - In an Editorial Comment in 2006 Carey summarized the issues surrounding the
      publication of case reports in the current medical literature. In this present
      study, three questions about case reports are posed by the author: Do journals
      still publish single case reports? What do medical journals call these reports?
      And how should we classify reports of single clinical observations? The author
      examined the table of contents of 25 prominent journals and addressed the
      question as to whether these selected periodicals published case reports. The
      analysis showed that 32% of reviewed journals published case reports and 32% did
      not, while the remainder of journals published this class of papers but in a
      modified fashion and not regularly. Journals varied in what term they use to
      describe case reports. The author proposed a classification system for case
      reports in the human genetics literature. More dialogue and research is needed to
      examine the role of case reports in the medical scientific literature.

PMID- 16964620
TI  - John M. Opitz Festschrift.

PMID- 16964621
TI  - Familial occurrence of multiple pterygium syndrome: expression in a heterozygote
      of the recessive form or variability of the dominant form?
AB  - We report on a case with apparently familial multiple pterygium syndrome (MPS).
      The proposita was a 3-year-old girl with classical symptoms of MPS. A careful
      clinical examination of the father disclosed the presence of few minor signs of
      the syndrome, including difficulty in opening the mouth widely, scoliosis, pectus
      excavatum, hands with slight cutaneous syndactyly, and bilateral single palmar
      creases. The radiograph of the hands disclosed malformed carpal bones and an
      altered metacarpal-phalangeal pattern. The father shows limited symptoms, which
      has been reported before in the autosomal dominant form of MPS. However, it is
      also possible that he is showing a heterozygous state of the autosomal recessive
      form of MPS. In conclusion, we emphasize the importance of examining accurately
      the parents of a child who has classical MPS phenotype, even those with normal
      stature and an absence of facial anomalies.

PMID- 16964622
TI  - 4q35 deletion and 10p15 duplication associated with immunodeficiency.
AB  - We report a familial cryptic reciprocal translocation between 4q35 and 10p15
      leading to deletion of the terminal long arm of chromosome 4 and duplication of
      the terminal short arm of chromosome 10 in two family members who both have
      immunological disturbances and a similar facial appearance. The precise location
      and extent of the deletion and duplication was determined by fluorescence in situ
      hybridization (FISH). Furthermore, we investigated the deletion breakpoint of a
      previously reported patient with 4q34.3-qter deletion [Van Buggenhout et al.
      (2004); Am J Med Genet Part A 131A:186-189].

PMID- 16964623
TI  - Plasmid system for the intracellular production and purification of affinity
      tagged proteins in Bacillus megaterium.
AB  - A multiple vector system for the intracellular high-level production of affinity
      tagged recombinant proteins in Bacillus megaterium was developed. The N- and C
      terminal fusion of a protein of interest to a Strep II and a His(6)-tag is
      possible. Corresponding genes are expressed under the control of a xylose
      inducible promoter in a xylose isomerase deficient host strain. The exemplatory
      protein production of green fluorescent protein (GFP) showed differences in
      produced and recovered protein amounts in dependence of the employed affinity tag
      and its N- or C-terminal location. Up to 9 mg GFP per liter shake flask culture
      were purified using one-step affinity chromatography. Integration of a protease
      cleavage site into the recombinant fusion protein allowed tag removal via tobacco
      etch virus (TEV) protease or Factor Xa treatment and a second affinity
      chromatographic step. Up to 274 mg/L culture were produced at 52 g CDW/L using a
      glucose limited fedbatch cultivation. GFP production and viability of the
      production host were followed by flow cytometry.

PMID- 16964624
TI  - Engineering promoter regulation.
AB  - Systems for easily controlled, conditional induction or repression of gene
      expression are indispensable tools in fundamental research and industrial-scale
      biotechnological applications. Both native and rationally designed inducible
      promoters have been widely used for this purpose. However, inherent regulation
      modalities or toxic, expensive or inconvenient inducers can impose limitations on
      their use. Tailored promoters with user-specified regulatory properties would
      permit sophisticated manipulations of gene expression. Here, we report a
      generally applicable strategy for the directed evolution of promoter regulation.
      Specifically, we applied random mutagenesis and a multi-stage flow cytometry
      screen to isolate mutants of the oxygen-responsive Saccharomyces cerevisiae DAN1
      promoter. Two mutants were isolated which were induced under less-stringent
      anaerobiosis than the wild-type promoter enabling induction of gene expression in
      yeast fermentations simply by oxygen depletion during cell growth. Moreover, the
      engineered promoters showed a markedly higher maximal expression than the
      unmutated DAN1 promoter, under both fastidious anaerobiosis and microaerobisois.

PMID- 16964625
TI  - Aspirin reduces platelet aggregation during high-energy excimer laser.
AB  - BACKGROUND AND OBJECTIVES: Excimer laser is used clinically in arterial
      revascularization procedures. This study evaluated the efficacy of aspirin in
      reducing platelet aggregation during high-energy excimer lasing. STUDY
      DESIGN/MATERIALS AND METHODS: Platelet rich plasma (PRP) from seven rabbits was
      circulated in a dual organ chamber with aspirin added to one and the other was
      control. PRP was irradiated using an excimer laser (308 nm; 45 mJ/mm(2); 25 Hz; 5
      minutes) via a 2.0 mm laser catheter. Platelet aggregation (particle volume) was
      measured by laser-light scattering. Morphology was evaluated by phase contrast
      and electron microscopy. RESULTS: Baseline platelet volume was 3.4 microm(3) for
      both control and aspirin groups. Following lasing, platelet volume peaked at
      102.2 +/- 18.5 microm(3) for control compared to 43.1 +/- 49.2 microm(3) for
      aspirin-treated PRP (P < 0.0001). CONCLUSION: Aspirin reduces large platelet
      aggregates but not small aggregates by 58% during lasing of PRP.

PMID- 16964626
TI  - Spirituality and clinical care in eating disorders: a qualitative study.
AB  - OBJECTIVE: Historical and contemporary research has posited links between eating
      disorders and religious asceticism. This study aimed to examine relationships
      between eating disorders, religion, and treatment. METHOD: Qualitative study
      using purposeful sampling, applying audiotaped and transcribed depth interview,
      subjected to interpretative phenomenological analysis. RESULTS: Participants were
      10 adult Christian women receiving inpatient treatment for anorexia or bulimia
      nervosa. Five dominant categories emerged: locus of control, sacrifice, self
      image, salvation, maturation. Appetitive control held moral connotations.
      Negative self-image was common, based more on sin than body-image. Medical
      treatment could be seen as salvation, with religious conversion manifesting a
      quest for healing, but treatment failure threatened faith. Beliefs matured during
      treatment, with prayer, providing a healing relationship. CONCLUSION: Religious
      beliefs impact on attitudes and motivation in eating disorders. Clinicians'
      sensitivity determines how beliefs influence clinical outcome. Treatment modifies
      beliefs such that theological constructs of illness cannot be ignored.

PMID- 16964627
TI  - 3-hydroxybenzene 1,2,4-trisphosphate, a novel second messenger mimic and unusual
      substrate for type-I myo-inositol 1,4,5-trisphosphate 5-phosphatase: Synthesis
      and physicochemistry.
AB  - 3-Hydroxybenzene 1,2,4-trisphosphate 4 is a new myo-inositol 1,4,5-trisphosphate
      analogue based on the core structure of benzene 1,2,4-trisphosphate 2 with an
      additional hydroxyl group at position-3, and is the first noninositol based
      compound to be a substrate for inositol 1,4,5-trisphosphate 5-phosphatase. In
      physicochemical studies on 2, when three equivalents of protons were added, the
      (31)P NMR spectrum displayed monophasic behaviour in which phosphate-1 and
      phosphate-2 behaved independently in most of the studied pH range. For compound
      4, phosphate-2 and phosphate-4 interacted with the 3-OH group, which does not
      titrate at physiological pH, displaying complex biphasic behaviour which
      demonstrated co-operativity between these groups. Phosphate-1 and phosphate-2
      strongly interacted with each other and phosphate-4 experienced repulsion because
      of the interaction of the 3-OH group. Benzene 1,2,4-trisphosphate 2 is resistant
      to inositol 1,4,5-trisphosphate type I 5-phosphatase catalysed dephosphorylation.
      However, surprisingly, 3-hydroxybenzene 1,2,4-trisphosphate 4 was
      dephosphorylated by this 5-phosphatase to give the symmetrical 2,3
      dihydroxybenzene 1,4-bisphosphate 16. The extra hydroxyl group is shown to form a
      hydrogen bond with the vicinal phosphate groups at -15 degrees C, and (1)H NMR
      titration of the ring and hydroxyl protons in 4 shows the OH proton to be
      strongly stabilized as soon as the phosphate groups are deprotonated. The effect
      of the phenolic 3-OH group in compound 4 confirms a critical role for the 6-OH
      group of the natural messenger in the dephosphorylation mechanism that persists
      even in radically modified analogues.

PMID- 16964628
TI  - Meta-analysis of endoscopy and surgery versus surgery alone for common bile duct
      stones with the gallbladder in situ.
AB  - BACKGROUND: There is no clear consensus on the better therapeutic approach
      (endoscopic versus surgical) to choledocholithiasis. This study is a meta
      analysis of the available evidence. METHODS: A search of the Medline and ISI
      databases identified 12 studies that met the inclusion criteria for data
      extraction. The analysis was performed using a random-effects model. The outcome
      was calculated as an odds ratio (OR) or relative risk (RR) with 95 per cent
      confidence intervals (c.i.). RESULTS: Outcomes of 1357 patients were studied.
      There was no significant difference in successful duct clearance (OR 0.85 (95 per
      cent c.i. 0.64 to 1.12); P = 0.250), mortality (RR 1.79 (95 per cent c.i. 0.66 to
      4.83); P = 0.250), total morbidity (RR 0.89 (95 per cent 0.71 c.i. to 1.13); P =
      0.350), major morbidity (RR 1.34 (95 per cent c.i. 0.92 to 1.97); P = 0.130) or
      need for additional procedures (OR 1.37 (95 per cent c.i. 0.82 to 2.29); P =
      0.230) between the endoscopic and surgical groups. There was also no significant
      difference between the endoscopic and laparoscopic surgery groups. CONCLUSION:
      Both approaches have similar outcomes, and treatment should be determined by
      local resources and expertise.

PMID- 16964629
TI  - IRBs: going too far or not far enough?

PMID- 16964630
TI  - Cholera toxin B subunit binding does not correlate with GM1 expression: a study
      using mouse embryonic neural precursor cells.
AB  - Gangliosides, sialic acid-containing glycosphingolipids, are ubiquitously
      expressed in all eukaryotic cells and are primarily localized in the plasma
      membrane. Cholera toxin B subunit (Ctxb), a component of a heat-labile
      enterotoxin produced by Vibrio cholerae, has been frequently used as a probe to
      detect GM1 ganglioside because of its high affinity for this glycolipid. In this
      study, we evaluated the reactivity of Ctxb and the expression of GM1 in mouse
      embryonic neuroepithelial cells (NECs). Analysis of Ctxb reactivity of NECs based
      on flow cytometry revealed that about 80% of the cells are Ctxb positive. A
      detailed biochemical analysis, however, indicated that GM1 was expressed in NECs
      in barely detectable quantities. Thus, it was thought that reactivity of Ctxb in
      the NECs could arise from high-affinity interaction with GM1. Because Ctxb is
      commonly used as a reagent for flow cytometry and GM1 cell staining, we recommend
      that using this reagent alone would be inconclusive and that biochemical analysis
      of GM1 should also be performed to avoid overestimation of GM1 expression and/or
      mischaracterization of the ganglioside species.

PMID- 16964631
TI  - Prevalence of low HDL-cholesterol levels and associated factors among Koreans.

PMID- 16964633
TI  - Death due to a stingray barb piercing the heart: a New Zealand case from 1939. An
      unusual bathing fatality.

PMID- 16964632
TI  - Delayed hypersensitivity to hydroxychloroquine manifested by two different types
      of cutaneous eruptions in the same patient.
AB  - Hydroxychloroquine (HXQ) sulphate is a synthetic antimalaria drug that is widely
      used in rheumatology due to its immunosuppressive properties. Delayed-type
      sensitization to this drug is rare. A 47-year-old woman diagnosed with HLA B27
      ankylosing spondylitis was treated with HXQ for 22 days and had to discontinue
      the drug due to gastric intolerance. Five days later the patient developed
      erythema multiforme (EM) with an extensive and unusual distribution. Patch test
      with 10% HXQ in DMSO were positive at 48 hours. Eight days later a generalized
      pruriginous erythematous papular exanthema developed, and a skin biopsy was
      obtained. The first reaction was EM. Patch-testing elicited systemic eczematous
      contact dermatitis. We report two different clinical patterns of delayed
      hypersensitivity in the same patient and with the same drug.

PMID- 16964634
TI  - Pharmacy conscience clause statutes: constitutional religious "accommodations" or
      unconstitutional "substantial burdens" on women?

PMID- 16964635
TI  - Molecular cloning and expression of a cDNA encoding a novel isoenzyme of protein
      kinase C (nPKC). A new member of the nPKC family expressed in skeletal muscle,
      megakaryoblastic cells, and platelets.

PMID- 16964636
TI  - Reacting to antibiotic allergies.
AB  - About 10-15% of all adults report that they are allergic penicillin or other
      antibiotics, although the accuracy and significance these reports remain unclear.
      In the outpatient setting, clinicians face a dilemma in prescribing for patients
      with a history of an allergic reaction to antibiotics. Which drugs should these
      patients avoid? Are these patients at increased risk for an allergic reaction to
      related drugs? This Issue Brief summarizes several large studies that can help
      guide improve the management of patients with antibiotic allergies.

PMID- 16964637
TI  - Corporate finance and consolidation in health care.

PMID- 16964638
TI  - [Progression on the molecular mechanism and management of early myocardial injury
      after severe burns].

PMID- 16964639
TI  - [Internal organ injury and its management after burns--a new progression of
      burns].

PMID- 16964640
TI  - [Influence of carbachol on intestinal dysfunction after traumatic or burn
      injury].
AB  - OBJECTIVE: To investigate the influence of enteral administration of carbachol on
      the intestinal dysfunction of both severely burn patients and rabbits with
      partial intestinal ischemia/reperfusion (I/R) injury. METHODS: Seventy-five white
      rabbits were inflicted with I/R injury and randomized into intestinal I/R (I,
      n=25), carbachol [C, n=25, with 3g/L carbachol (3 mg/kg) injection into duodenum
      1 h after SMA occlusion] and sham operation (SO, n=25, with SMA isolation but no
      occlusion) groups, and 5 other as normal controls. The blood flow of intestinal
      mucosa was detected before and after SMA occlusion or admission of carbachol.
      Changes in diamine oxidase (DAO), D-lactate, xylopyranose absorption, blue
      dextran discharging time were measured at 2, 4, 6, 8, 24, 48, 72 h after SMA
      occlusion. In addition, eight severe burn patients with TBSA of 84 +/- 12% were
      enrolled in the study, and carbachol (15 microg/kg) was administered to patients
      when abdominal distension or bowel sound was lower than 2 times/min, then the
      number of abdominal distension and bowel sounds per minute were observed.
      RESULTS: The blood flow in intestinal mucosa of rabbits without SMA occlusion was
      (102 +/- 5) PU, reduced to (48 +/- 6) PU after SMA occlusion, and increased to
      (77 +/- 3) PU after injection of carbachol. The plasma DAO activity and D-lactic
      acid content in I group began to increase 4 hours after SMA occlusion, and they
      reached the peak 24 hours after SMA occlusion (4.63 +/- 0.27 U/ml, 7.9 +/- 2.4
      mg/L) , after that they decreased gradually, but still higher than the normal
      value (0.89 +/- 0.14 U/ml, 2.0 +/- 1.1 mg/L, P < 0.05). In carbachol group, data
      showed the same trends as that in intestine I/R group with lower values, while no
      obvious changes were in sham operation group (P > 0.05). The content of D-lactic
      decreased dramatically 2 hours after D-lactic administration in both I and C
      groups, increased 6 hours after SMA occlusion, then decreased gradually, but it
      in C group was always higher than normal values, and little fluctuation was in
      sham operation group. There was no blue dextran discharge 2 hours after SMA
      occlusion. The discharging distance increased 6 hours later, but it was obviously
      shorter than the normal value 24 hrs after operation (P < 0.05) , then it
      returned to normal 48 to 72 hrs after operation. In the C group, blue dextran
      discharge was found immediately after its injection, with obvious increase in the
      discharging distance to peak value (43 +/- 6 cm) 6 hours after injury, and
      returning to normal (28 +/- 3 cm) gradually. In severe burned patients, the bowel
      sounds was (1.6 +/- 1.1) per minutes before carbachol administration, then
      increased dramatically to (6.9 +/- 1.7) per minutes 10 mins after administration,
      reached to a higher level 30 minutes after administration (8.3 +/- 2.4 )
      times/min, and it maintained to (6.1 +/- 1.3) times/min 1 hour after
      administration. Abdominal distension was ameliorated 2 hours after carbachol
      administration, six patients were able to defecate. CONCLUSION: Enteral
      administration of Carbachol can increase the blood flow of intestine mucosa, help
      to improve the movement, absorption and barrier functions of intestine, and
      ameliorate intestinal dysfunction in patients with severe burns.

PMID- 16964641
TI  - [Study on the mechanism of alleviation of myocardial injury after early
      escharectomy en masse of several burns in rat].
AB  - OBJECTIVE: To investigate the alleviation of myocardial injury of rats after
      early escharectomy en masse of severe burns, and to explore its molecular
      mechanism. METHODS: Totally 66 SD rats were randomly divided into normal control
      (n=6), non-escharectomy (NE, n=30) and escharectomy (E, n=30, with total
      escharectomy 20 minutes after burns ) groups. The rats in the NE and E groups
      were inflicted with 30% TBSA full-thickness scald. The content of ATP in
      mitochondria, troponin I (Tn I) in serum and 4.8-kb deletion of myocardial
      mitochondrial DNA (mtDNA) of the rats in each group were determined at 1, 3, 6,
      12 and 24 post-scald hours (PSH). RESULTS: (1) The content of ATP in myocardial
      mitochondria was decreased in both E and NE groups, but it was obviously
      increased at 1 and 6 PSH (0.90 +/- 0.27 microg/mg 0.66 +/- 0.19 microg/mg) in E
      group when compared with those in NE group (0.74 +/- 0.18 microg/mg, 0.46 +/-
      0.21 microg/mg, P < 0.05). (2) There was no obvious change in the serum content
      of Tn I in E group at 1 and 3 PSH, but the respective content in 1, 3 and 6 PSH
      was markedly lower than those in NE group (P < 0.05). (3) The 4.8 kb deletion of
      myocardial mtDNA was found at 1, 3, 24 PSH in NE group, while it was observed
      only at 1, 12 PSH in E group. The partial and whole deletion rate in E group was
      lower than that in NE group. CONCLUSION: Early escharectomy en masse can
      significantly alleviate the myocardial injury after burns,which might be related
      to its effect in lowering the deletion rate of myocardial mtDNA at early postburn
      stage.

PMID- 16964642
TI  - [Effect of antisense oligonucleotide against Smac/DIABLO on inhibition of
      hydrogen peroxide induced myocardial apoptosis of neonatal rats].
AB  - OBJECTIVE: To investigate the effects of antisense phosphorothioate
      oligonucleotides against Smac/DIABLO (asODN) on hydrogen peroxide (H2O2) induced
      myocardial apoptosis in neonatal rats. METHODS: Primary myocardial cells from
      neonatal rats were cultured in vitro, and randomly divided into A (normal
      control, without transfection), B (with treatment of single liposome), C (with
      transfection of scrODN), D (with transfection of asODN), E (with H2O2,
      stimulation), F (with H2O2 stimulation after scrODN transfection), and G (with
      H2O2 stimulation after asODN transfection) groups. The expression of asODN mRNA
      and protein were determined with RT-PCR and Western blotting, respectively. The
      changes in cellular nuclear morphology were observed with 33258 fluorescent
      staining, and the percentage of nuclear apoptosis was calculated. DNA
      fragmentation was observed by agarose gel electrophoresis. Activation of caspase
      3 and caspase-9 were evaluated by caspase colorimetric analysis kit. RESULTS: The
      expression of Smac/DIABLO mRNA and protein was obviously inhibited by asODN,
      which was about 80% percent lower than the protein level in A,B and C groups, but
      there was no difference noted among A,B and C groups( P > 0.05). Not only the
      nuclear apoptotic percentage, but also the activity of caspase-3 and caspase-9 in
      A, C and D groups were in very low levels. But these indices in G group 24 hours
      after H2O2 stimulation were obviously lower than that in E and F groups [the
      nuclear apoptotic percentage were (19 +/- 5) %, (52 +/- 3) %, (55 +/- 5) %,
      respectively, P < 0.01)]. The DNA ladders in G group were also decreased
      markedly. CONCLUSION: Myocardial apoptosis induced by H2O2 can be inhibited by
      asODN in rat.

PMID- 16964643
TI  - [Effect of ulinastatin on the management of early myocardiac injury after severe
      burns].
AB  - OBJECTIVE: To investigate the effect of Ulinastatin on the management of early
      myocardial injury and its mechanisms. METHODS: Thirty-four severe burn patients
      with TBSA exceeding 50% were admitted into our hospital within 24 hrs after
      burns, and they were divided into burn group (n=17) and ulinastatin-treated group
      (n=17, UTI group). All patients received conventional treatment. The patients in
      UTI group were given 100,000 U ulinastatin intravenously immediately after
      admission, 3 times a day for a week. The plasma content of troponin I (cTnI) ,
      creatine kinase (CK-MB) and PMN elastase were determined on 2, 4 and 7 postburn
      days (PBD), and the correlate relationship among these three indices were
      analyzed. RESULTS: (1) The plasma content of cTnI and PMN elastase at 2, 4, 7
      PBDs were significantly higher than that of normal value (P < 0.01), but they
      were obviously lower in UTI group than that in burn group. (2) Compared with
      normal value, the plasma content of CK-MB in burn group was increased
      significantly on 2, 4 and 7 PBDs (P < 0.01), and it reached the peak on 4 PBD.
      Though it was obviously higher in UTS group on 2 and 4 PBDs compared with the
      normal value, but it was lower than that in burn group ( P < 0.05 or 0.01) , and
      it returned to normal value on 7 PBD. (3) There exhibited positive correlation
      among the PMN elastase content, cTnI content and CK-MB activity of the 34
      patients. The correlation index of PMN elastase content and cTnI content was 0.
      904, while that between cTnI content and CK-MB activity was 0.922, and that
      between PMN elastase content and CK-MB activity was 0.829 (P < 0.01). CONCLUSION:
      Ulinastatin is beneficial in alleviating myocardial injury after severe burns,
      and it reduces the release of PMN elastase.

PMID- 16964644
TI  - [Influence of lipopolysaccharide and burn sera on ion channels in smooth muscle
      cells of colon of guinea pig].
AB  - OBJECTIVE: To investigate the influence of lipopolysaccharide (LPS) and burn sera
      on potassium channels (Kca) in smooth muscle cells of colon of guinea pig so as
      to elucidate the molecular mechanism of gastrointestinal motility dysfunction
      after severe burns. METHODS: Single smooth muscle cells were isolated from the
      taenia coli of guinea pig with enzyme digestion. The standard patch clamp
      technique was employed to record the single KCa channel currents of smooth muscle
      cell after challenged by LPS and burn serum. Data were recorded and analyzed by P
      clamp 6.04 software, and the probability of open (PO), mean open time (OT), mean
      close time (CT) and current amplitude (CA) were determined. Subsequently, LPS in
      the concentration of 20, 40, 60, 80 and 100 mg/L, respectively, and normal serum
      and burn serum in the concentration of 10% were respectively added into medium to
      examine the influence of the two clamps and sera on the KCa activity. RESULTS: In
      hyperkalemic solution, the KCa conductance of colonic smooth muscle cells of the
      guinea pig was (271 +/- 7) pS, indicating it was an ionic channel with high
      conductivity. Subsequent to depolarization of the membrane, inner-cellular
      calcium level was increased, and channel PO was also increased, which could be
      blocked by 1 mmol/L tetraethylammonium (TEA) outside the membrane chaff. As 40
      mmol/L TEA inside the membrane chaff did not show such effect, it was proved to
      be KCa current. The activity of the channel as determined with two kinds of
      clamps was increased in a dose dependent manner with LPS challenge when the
      concentration of calcium was 0 mol/L. The KCa activity and PO of the channel was
      increased obviously when the concentration of LPS was above 40 mg/L (P < 0.05 or
      0.01), and it could not be reversed after irrigation with non-LPS medium. By
      using the two kinds of patch clamps, the KCa were activated by burn sera, but not
      normal sera. CONCLUSION: Both LPS and burn sera can lead to inhibition of the
      gastrointestinal motility by activation of KCa channels.

PMID- 16964645
TI  - [Prolongation of the survival of skin allografts by intravenous injection of
      neuraminidase-treated donor bone marrow cells in rats].
AB  - OBJECTIVE: To optimize the best concentration of neuraminidase (Neu) that
      enhances the migration of neuraminidase (Neu)-treated donor bone marrow cells
      (dBMCs) to the liver, and observe the influence of short-term cyclosporin A(CsA)
      application combined with intravenous injection (i.v.) of Ne treated dBMCs on the
      survival of skin allografts. METHODS: The experiment consisted of two parts. For
      selection of an appropriate concentration of Neu, 26 female Wistar rats were
      randomly divided into four groups. The dBMCs were prepared by routine method and
      treated with four concentrations (0, 0.5, 1.0, 2.0 U/ml) of Neu at 37 degrees C
      for 30 min. The untreated and Neu-treated dBMCs were labeled by 99mTc, and
      injected via the tail veins to female Wistar rats in each group, respectively.
      After five hours, the radioactivity of various organs collected from sacrificed
      rats was measured by a gamma counter, and the values were expressed as percentage
      of total radioactivity of all organs from the same rat. To observe the survival
      of skin allograft, 23 male Wistar rats were randomly divided into control group,
      untreated dBMCs group and Neu-treated dBMCs group. All rats in each group were
      grafted with skin allografts from male Sprague-Dawley (SD) rats. The dBMCs from
      the same donor without and with Neu treatment by the concentration selected from
      the above experiment were injected via the tail veins of female Wistar rats in
      untreated dBMCs group and Neu-treated dBMCs group, respectively. Rats in
      untreated dBMCs group and Neu-treated dBMCs group received CsA (10 mg/kg) through
      intraperitoneal injection (i.p.) at 2 and 5 days post-grafting. Neither dBMCs or
      CsA were given in the control group. The survival of allograft skin in each group
      was checked and photographed daily after 5 days post operation. RESULTS: When the
      concentration of Neu was 1.0 U/ml, the percentage of dBMCs in liver was (75.3 +/-
      9.8) %, which was obviously higher than that in 0 U/ml group [(58.9 +/- 4.2%)],
      (P < 0.01), indicating that the optimal concentration of Neu was 1.0 U/ml. The
      survival time of skin allografts in rats of Neu-treated dBMCs group was prolonged
      significantly in comparison with that of the rats in dBMCs group without Neu
      treatment (P < 0.01). The survival time in both dBMCs group and Neu-treated dBMCs
      group was longer that of control group (P < 0.01), and it was prolonged in Neu
      treated dBMCs group compared with that in dBMC group. CONCLUSION: Administration
      of proper concentration of Neu can increase the affinity of dBMCs to the liver,
      and promote the Neu-treated dBMCs to migrate to liver. The intravenous injection
      of Neu-treated dBMCs combined with short-term CsA administration can delay the
      rejection of skin allografts in rats.

PMID- 16964646
TI  - [Influence of substance P on the release of histamine in the human hypertrophic
      scar tissue].
AB  - OBJECTIVE: To investigate the influence of substance P (SP) on the release of
      histamine in the human hypertrophic scar tissue, and to explore the prerequisite
      of their interaction. METHODS: Tissue specimens of normal skin and hypertrophic
      scar from eight hospitalized patients were excised and cut into 0.5 to 1.0 mm3
      pieces, and the histamine release by mast cell (MC) under the stimulation of
      different concentration of SP and calcium, as well as the different affect time
      of SP, were determined with fluorescence spectrometer. Then the histamine release
      rate was calculated. RESULTS: There was obvious release of histamine when SP
      concentration was 1 x 10(-6) mol/L , and the release rate was (50.0 +/- 3.6) %,
      which was significantly higher than that by SP in the concentration of 0 mol/L
      [(44.0 +/- 3.2) %, P < 0.01]. Therefore it seemed to be dose-dependent. About 90%
      of histamine was released within 15 minutes of 5 x 10(-1) mol/L Substance P
      stimulation, and it was also time-dependent. The histamine release reached the
      peak when calcium concentration was 5 x 10(-3) mol/L, which seemed to be dose
      dependent, but it decreased transiently when calcium concentration was 1 x 10(-3)
      mol/L. In all occasions, the influence of SP on the histamine release by MC in
      hypertrophic scar (HS) was markedly higher than that in normal skin (NS) (P <
      0.01). Conclusion The influence of SP on the histamine release by MC in HS was
      markedly higher than that in NS, and it might be closely related to itching
      sensation and the formation of hypertrophic scar.

PMID- 16964647
TI  - [Study on the influence of hypoxia induced microtubule damage on the opening of
      mitochondrial permeable transition pore of cardiac myocytes in rat].
AB  - OBJECTIVE: To investigate the influence of hypoxia induced microtubule damage on
      the opening of mitochondrial permeable transition pore (MPTP)of cardiac myocytes
      and on the decrease of respiratory function in rat. METHODS: Primary cultured
      myocardial cells from 30 neonatal rats were randomized as normoxic group (A),
      hypoxia group (B), normoxia with microtubule destabilizing agent group (C, with
      treatment of 8 micromol/L colchicines for 30 minutes before normoxia), and
      hypoxia with microtubule stabilizing agent group (D, with treatment of 10
      micromol/L taxol for 30 minutes before hypoxia). beta-tubulin immunofluorescence
      ,the opening of mitochondria permeability transition pore, and the mitochondrial
      inner membrane potential were detected at 0.5, 1, 3, 6 and 12 post-treatment
      hours (PTH), and the mitochondrial respiratory function was determined by MTT
      method. The changes in these indices were also determined in A group at the
      corresponding time-points. RESULTS: Obvious damage of polymerized microtubule,
      opening of MPTP, mitochondrial inner membrane potential loss and decrease of
      myocardial respiratory activity were observed in both group B and C at 0.5 PTH,
      and they became more and more serious afterwards. However, the changes in the
      above indices in D group were much better than those in B group (P < 0.05 or
      0.01), and no difference was found between D (92.8 +/- 4.0)% and C [(100.0 +/-
      0.0) %, P > 0.05] groups. CONCLUSION: Hypoxia played a role in the myocardial
      microtubule damage as well as in the opening of MPTP. Moreover, hypoxia could
      also impair the mitochondrial respiratory function. Microtubule destabilizing
      agent could reproduce well the process of hypoxia induced microtubule damage,
      while the stabilizing agent exerted protective effect by improving the transition
      of mitochondrial permeability and the mitochondria respiratory function.

PMID- 16964648
TI  - [Primary study on the culture of human fetal follicle bulge cells and their
      differentiation into sebaceous gland].
AB  - OBJECTIVE: To develop a rapid and reproducible method for the culture of human
      fetal hair follicle bulge cells, and observe the plasticity of its
      differentiation into sebaceous gland in vitro. METHODS: The bulge cells isolated
      from fetal human hair follicles by enzymatic digestion (digestion method) and
      manual microdissection (conventional method) were cultured and passaged
      respectively, the efficiency and biological features of cells were investigated ,
      the clone forming efficiency was assayed by MTT, and the expression of K19 was
      further compared by immunocytochemistry (ABC). The morphological change and the
      expression of EMA of bulge cells were also observed after induction. RESULTS: By
      conventional method, 8-10 bulges were harvested in one hour, 40%-50% of their
      cells were found to adhere to the culture plate after culturing for 48h, and they
      became confluent after 14 days. In comparison, about 100 bulges were harvested in
      one hour by digestion method, the adherence efficiency of their cells was 30%
      after cultivation for 12h and became confluent after 7 days. The cells grew
      larger with time, with irregular shape and droplets of lipid around the nucleus.
      The clone forming efficiency of bulge cells cultured by digestion method was
      (18.2 +/- 2.1) %, which was much higher than that of cells obtained by
      conventional method[ (12.7 +/- 3.4) %, P < 0.05]. Immunocytochemistry staining
      showed that positive staining of K19 was observed in most of the bulge cells,
      with a large amount of brown granules in the cytoplasm. CONCLUSION: Human hair
      follicle bulge cells can be efficiently cultured and multiplied in vitro, and
      they retained the characteristics of stem cells. And they have the potential to
      differentiate into sebaceous glands by induction in vitro.

PMID- 16964649
TI  - [Influence of liposome induced gene transfection on the characteristics of human
      immature dendritic cells].
AB  - OBJECTIVE: To investigate the influence of liposome induced gene transfection on
      the phenotypic characteristics and immune function of human immature dedritic
      cells (imDC). METHODS: Monocytes were isolated from human cord blood, and they
      were differentiated into imDC by rhGM-CSF and rhIL-4 induction. Then the
      morphologic observation and immune phenotypic identification were performed in im
      DCs. imDCs were divided into transfection (T, with liposome transfection of pEGFP
      vector) and control (C, without transfection) groups. The transfection rate and
      expression of cell maturation marker (CD83, CD86 and HLA-DR) were determined with
      flow cytometry, and the proliferation of non-sensitized T lymphocyte before and
      after transfection was determined with allogeneic mixed leukocyte reaction (MLR).
      RESULTS: im-DC derived from human cord blood cells had typical appearance and
      surface markers consistent to what reported in the literature. The expression
      rates of CD86, CD83 and LA-DR in T group were (12 +/- 6) %, (8.6 +/- 2.3) % and
      (71 +/- 7) %, respectively, which exhibited no difference compared with those in
      C group (13 +/- 6) %, (9.1 +/- 3.8) % and (72 +/- 8) %, (P > 0.05). MLR results
      indicated that there was no obvious change in the immune stimulation function of
      imDC after transfection (P > 0.05) , with stimulation index lower than 2.
      CONCLUSION: There is no change in maturation of imDC after liposome transfection,
      but the transfection efficiency needs to be elevated.

PMID- 16964650
TI  - [The antagonistic effect of recombinant human decorin on TGF-beta1 stimulation of
      fibroblasts in collagen lattices].
AB  - OBJECTIVE: To mimic contact pattern between decorin and TGF-beta1, in vivo, and
      investigate the antagonistic effect of recombinant human decorin on TGF-beta1
      stimulation of hypertrophic scar fibroblasts in collagen lattices. METHODS:
      Fibroblasts populated collagen lattices (FPCL) model was adopted in the study,
      and they were divided into control group, decorin group [2mg/L recombinant human
      decorin (rh-decorin) was administered to FPCL], TGF-beta1 group (5 microg/LTGF
      beta1 was administered to the culture medium), and TGF-beta1 + decorin group
      (2mg/L rh-decorin was administered to FPCL, then culture medium containing 5
      microg/L TGF-beta1 was added into FPCL). Changes in PAI-1 and alpha-SMA protein
      expression in scar fibroblasts in collagen lattices were detected with Western
      blotting at 12 post-administration hour (PAH), 24 PAH, 48 PAH, and 72 PAH, and
      expressions of PAI-1 and alpha-SMA mRNA were concomitantly examined by RT-PCR.
      RESULTS: The contraction of FPCL at each time-point in control group was
      obviously attenuated compared with that in decorin group, but it was
      significantly intensified compared with that in TGF-beta1 group. The expression
      of PAI-1 and alpha-SMA mRNA and protein in TGF-beta1 group (3482 +/- 211, 4320 +/
      272, 0.89 +/- 0.15, 0.56 +/- 0. 11) were markedly increased than those in
      control group (1764 +/- 147, 1699 +/- 146, 0.29 +/- 0.06, 0.21 +/- 0.06, P <
      0.01), while no obvious difference of them was found between control and other
      two groups. CONCLUSION: Stimulation of scar fibroblasts by TGF-beta1, can be
      suppressed when rh-decorin is blended into collagen lattices, indicating that
      decorin is effective in neutralizing TGF-beta1 in vitro. The pathogenesis of
      hypertrophic scar might be related to up-regulation of TGF-beta1 with the lack of
      decorin after cutaneous injury.

PMID- 16964651
TI  - [The influence of antigen loading on the immunological characteristics of
      dendritic cells induced by low concentrations of granulocyte macrophage colony
      stimulating factor].
AB  - OBJECTIVE: To investigate the influence of low doses of granulocyte macrophage
      colony stimulating factor on the allogeneic antigen (Ag) ingestion capacity of
      immature dendritic cells (GM low DC), and subsequently the changes in the
      cellular phenotype and function. METHODS: Mononuclear cells from C57BL/6 mice was
      labelled with 3H-Leu to make Ag supernatant. The Ag supernatant was cocultured
      with GM low DC or mature DC for 30,60 and 90 mins, then cpm value were
      determined. The changes in I(A)/I(E) and CD80 on cell surface after antigen
      ingestion were determined with flow cytometry (FCM). By using mixed lymphocyte
      reaction (MLR), the cells were divided into control (non-sensitized T
      lymphocyte), GM low DC, GM low DC and allogeneic antigen, GM low DC and
      allogeneic antigen and CTLA-4 Ig groups. The cpm value in each group was recorded
      and the stimulation index (SI) was calculated. RESULTS: Upon 30, 60 and 90 mins
      of allogeneic Ag stimulation, the cpm value of GM low DC was obviously higher
      than that of mature DC (P < 0.05 or 0.01). In addition, the expression of
      I(A)/I(E) and CD80 before allogeneic Ag ingestion were significantly higher than
      those after Ag ingestion (I(A)/I(E): 32 +/- 8% vs. 54 +/- 10, P < 0.05; CD80: 25
      +/- 10% vs. 71 +/- 18%, P < 0.01). MLR: Compared with control group, the cpm
      value in GM low DC with allogeneic Ag group was increased markedly (P < 0.05),
      with SI higher than 2.0, while no difference was found among control, GM low DC
      group, GM low DC and allogeneic Ag and CTLA-4Ig groups (P > 0.05), with SI lower
      than 2.0 CONCLUSION: Though GM low DC exhibits powerful antigen ingestion
      capacity, the cell phenotype and function will get mature gradually. Immune
      tolerance can be established by incubating GM low DC with CTLA-4Ig.

PMID- 16964652
TI  - [Influence of sea water immersion on inflammation and healing of the wounds in
      scalded rats].
AB  - OBJECTIVE: To investigate the influence of sea water immersion on inflammation
      and healing of the wounds in scalded rats. METHODS: One hundred and forty-four
      male Wistar rats with 10% TBSA superficial partial-thickness scald were randomly
      divided into A (n=72, with scald) and B (n=72, with seawater immersion for 4hrs
      immediately after scald) groups. The serum contents of K+, Na+, Cl- were
      determined at 0 post-scald hour (PSH), 6PSH, 12PSH and 24 PSH with electrocyte
      analysis apparatus, and the changes in serum interleukin-6 (IL-6) and tumor
      necrosis factor (TNF-alpha) levels were determined at 0 PSH, 6PSH and 12 PSH with
      enzyme-linked immunosorbent assay (ELISA). The histopathological changes in the
      rats of the two groups were observed, and wound healing time was respectively
      calculated. RESULTS: The serum contents of K+, Na+, Cl- in B group were obviously
      higher than those in A group. And the serum content of TNF-alpha and IL-6 in B
      group at 6 PSH [(140 +/- 22) ng/L, (160 +/- 41) ng/L] were significantly higher
      than those before scald [(29 +/- 15) ng/L, (62 +/- 17)] ng/L and in A group [(120
      +/- 12) ng/L, (124 +/- 22) ng/L, ( P < 0.05)]. Compared with A group, re
      epithelization of the wound differentiation in all layers of epidermis were
      delayed in B group, with more severe wound swelling, exudation, and topical
      inflammatory response. The wound healing time in B group was (16.3 +/- 1.6) d,
      which was obviously longer than that in A group [(14.1 +/- 1.8) d, P < 0.05)].
      CONCLUSION: Sea water immersion combined with scald injury can aggravate the
      inflammatory response of the wound and delay the wound healing process.

PMID- 16964653
TI  - [Inhibition of integrin beta1 expression in human keratinocyte stem cells by
      vector-1 based interfering RNA strategy].
AB  - OBJECTIVE: To investigate the influence of integrin beta1 on the proliferation
      and differentiation of human keratinocyte stem cells (KSCs). METHODS: DNA
      oligonucleotides targeting integrin beta1 at different locations were synthesized
      and inserted into BamHI-1 HindIII linearized p Silencer 3.1/H1 plasmids. The
      inserted sequences were verified by DNA sequencing. The KSCs were divided into
      control (without transfection), T1 (with transfection of vacant vector), T2 (with
      transfection of si integrin beta(1-1) vector), T3 (with transfection of si
      integrin beta(1-1) vector), and T4 (with transfection of si Negative vector)
      groups. The change in the expression of integrin beta1, was determined with
      Western blotting. The positive vector with the highest expression of integrin
      beta1 was selected and named as integrin beta1, and semi-quantitative RT-PCR was
      employed to detect the change in the expression of integrin beta1 mRNA. RESULTS:
      The protein expression of integrin beta1, was not suppressed in control and T1
      group, but it was suppressed in T2 and T3 groups, especially in T3 group (the
      suppression rate was 60%-70%, which was named si integrin beta1). The expression
      of integrin beta1 mRNA was obviously decreased by integrin beta1, transfection
      (the suppression rate was 70%). CONCLUSION: The expression of integrin beta1,
      mRNA and protein could be down-regulated with recombinant si integrin P, vector
      transfection.

PMID- 16964654
TI  - Not just child's play. With their unique ability to distract, educate, and
      entertain, video games are increasingly being used to help heal and soothe the
      sick.

PMID- 16964656
TI  - Theory of evolution. Did Darwin get scooped?

PMID- 16964655
TI  - Plan B: to shelve, or not to shelve. Emergency contraception is on the hot seat
      again.

PMID- 16964657
TI  - The double helix. Shining a light on the 'dark lady of DNA'.

PMID- 16964658
TI  - AIDS virus. The sound and fury of HIV.

PMID- 16964659
TI  - The graying of AIDS.

PMID- 16964660
TI  - Lights! Camera! Incision!

PMID- 16964661
TI  - [Quality of life and prosthodontics].
AB  - Orofacial pain, functional limitations, psychosocial impacts, and concern about
      appearance are all dimensions of oral health-related quality of life.
      Consequently, OHRQoL is especially important for prosthodontics. OHRQoL is
      assessed by multiple-item questionnaires that ask about numerous symptoms,
      problems and social impacts. 49 items into seven dimensions were developed in the
      OHIP which was then verified among several different cultural circumstances.
      Evaluating baseline (To) immediately after treatment (T1) and after a longer
      observation time (T2), a decrease of symptoms and problems could be followed in
      prosthodontic care. Fastest improvement in patient satisfaction was observed in
      case of fixed partial denture wearers. The profile of pre- and post-treatment
      problems differed extensively among removable partial and complete denture
      wearers, and only minor problems were found after a longer time of adaptation.
      OHIP instrument seems to be a reliable indicator of change in oral health-related
      quality of life, for cultural circumstances deviated largely from each others.

PMID- 16964662
TI  - [Sialorrhea: hypersalivation and drooling. An underestimated problem in medical
      practice].
AB  - On the contrary to hyposalivation/xerostomia there is a little attention paid in
      the literature for discussing the problem of the patient having too much saliva.
      In most of cases, pathogenesis of sialorrhea is not known. Due to the small
      number of patients involved in the studies it is difficult to get exact data. In
      addition to that, there is no consensus either on the terminology of sialorrhea
      or a preferable method which should be used to achieve the best diagnostic and
      therapeutic approaches. Sialorrhea may occur in all age groups of population
      either as a consequence of increased salivary gland secretion or oral
      incontinence and impaired swallowing. Based on a recently published paper
      hypersalivation should be considered as the primary form of sialorrhea, and
      drooling corresponds to its secondary form. Each condition may seriously affect
      the physical activity, the functioning of different organs, communication, the
      psychosocial status of the patients. Based on a wide horizon of published data
      this review is focused on the terminology, methods of assessment, etiology,
      frequency, symptoms, and therapy of sialorrhea with special emphasis on its
      dental aspects.

PMID- 16964663
TI  - [Construction of the new dental arch in the prosthetic rehabilitation of cleft
      lip and palate. Case report].
AB  - The authors describe the prosthodontic rehabilitation of an adult patient with
      unilateral cleft lip and palate. After the surgical and orthodontic treatment of
      cleft lip and palate patients the prosthodontic treatment was started to correct
      the palatal defect, the malocclusion and the missing teeth. The authors emphasize
      on preliminary steps by using diagnostic casts and try-in dentures and they also
      suggest other directives in the dental management of cleft lip and palate
      patients.

PMID- 16964664
TI  - [Prevalence of hypodontia in 4-18-year-old children in Department of Paediatric
      Dentistry, Faculty of Dentistry, University of Debrecen from 1999 to 2003].
AB  - Hypodontia is one of the most common human dental anomalies. Its management is
      often complicated. This survey was carried out to study the prevalence,
      localisation and combination of congenital aplasia in Department of Paediatric
      Dentistry, Faculty of Dentistry, University of Debrecen. The study group
      consisted of 669 children, 283 boys and 386 girls, aged 4-18 years.
      Orthopantomograms and clinical examinations were used for the retrospective
      study. The prevalence of hypodontia was found to be 7.76 percent, excluding the
      third molars. Most of the congenitally absent teeth were the upper lateral
      incisors and the lower second premolars. The most frequent combinations were the
      12-22 and the 35-45 ones. We found that our data were very similar to the
      different international results.

PMID- 16964665
TI  - [Prosthetic rehabilitation of an epilepsy patient with dental implants. Case
      report].
AB  - According to epidemiologic data patients with epilepsy generally have more
      caries, more missing teeth and worse periodontal status than the normal
      population. Epilepsy patients have a great risk of injury during their seizures
      or aspiration of foreign bodies such as removable dental prosthesis or fragments
      of prosthesis. Fixed dental replacements are therefore recommended to reduce this
      risk. In cases where the anatomic restrictions enable only a conventional
      removable prosthesis, an implant prosthetic treatment offers helpful alternative
      for the epileptic patient. The implant prosthetic treatment of a 48-year-old
      epileptic patient is presented. After inserting six dental implants into the
      lower jaw, three short span bridges were fabricated. The surgery was carried out
      under local anesthesia in the routine way. A bite plate was made for night use to
      avoid the crack of the ceramic surfaces during any possible seizure.

PMID- 16964666
TI  - [Report of the General Secretary of the Hungarian Dentists' Association at the
      Delegates' Meeting of May 12th, 2006].

PMID- 16964667
TI  - [Vaccination against hepatitis B and epidemiological situation of this disease in
      European countries in the years 1990-2001].
AB  - Programme of vaccination in 52 countries of European Region does not include
      vaccination against hepatitis B of newborns and infants in 13 countries (25,0%),
      of older children and adolescents in 28 countries (53,8%) and among them
      newborns, infants older children and adolescents in 8 countries (15,4%). The best
      coverage of vaccination was found in Italy, Bulgaria, Poland, Romain and
      Lithuania. Number of cases of hepatitis B in the years 1990-2001 in 10 countries
      among 22 (45,4%), decreased in 6 countries (27,2%), increased in 4 countries
      (18,2%). The biggest improvement of epidemiological situation of hepatitis B was
      found in Poland.

PMID- 16964668
TI  - [Coverage of vaccination against hepatitis B in Poland in 2004].
AB  - Vaccinations against hepatitis B were performed according to Programme of
      Vaccination since 1989. 31,1% of population was vaccinated at the and of 2004. In
      voivodships vaccination was performed between 38,2% and 27,6% Children and
      adolescents up to 19 years old were vaccinated in 77,6% and persons older than 20
      in 15,6%. In the next 2-4 years all children, adolescents and young adults up to
      23 should be vaccinated against hepatitis B in Poland in 95% or even more.

PMID- 16964669
TI  - [The influence of interferon-alpha-2b on the effectiveness of the hepatitis B
      vaccine in patients suffering from chronic hepatitis C].
AB  - The aim of our study was to investigate the immunogenicity of hepatitis B vaccine
      in a group of patients suffering from chronic heaptitis C. Thirthy seven patients
      with chronic hepatitis C (anti-HCV+, HCV-RNA+, histological findings) were
      selected. Only those patients without serological markers for HBV infection
      (HBsAg (-), anti-HBcT(-), anti-HBs (-)) were vaccinated the hepatitis B vaccine.
      The recombinant vaccine (Engerix-B SKB 20 microg) was used according to a 0, 1,2
      month regime. The vaccinees were divided into two groups. Group A-12 patients
      with HCV infection, were treated with interferon alpha 2b during vaccination.
      Group B-25 patients did not recive the interferon. The seroconversion rates and
      the concentrations of anti-HBs were taken at month 1, 2 and 3 after the first
      injection. RESULTS: Patients suffering from chronic hepatitis C react much less
      favorably to the hepatitis B vaccine than healthy subjects. Administration of the
      hepatitis B vaccine coupled with interferon-alpha treatment resulted in
      statistically significant improvement of the immunological response to the
      vaccine.

PMID- 16964670
TI  - [The comparison of the humoral response among the patients with liver cirrhosis
      and steatosis of the liver after HBV vaccination].
AB  - The goal of the study was the assessment of the effectiveness of the hepatitis B
      vaccine among patients with liver diseases. Only those patients without
      serological markers for HBV infection (HBsAg-, anti-HBcT-, anti-HBs-) were
      selected. Twenty nine patients were vaccinated. The recombinant vaccine (Engerix
      B SKB 20 microg) was used according to a 0, 1, 2 month regime. Serum samples for
      seroconversion rates and concentration of antiHBs were taken at month 1,2 and 3
      after the first injection. The vaccines were divided into two groups. Group 1-16
      patients with liver steatosis. Group 2-13 patients suffering from liver
      cirrhosis. The seroconversion rates and the concentrations of anti-HBs were taken
      at month 1,2 and 3 after the first injection. Good response to the HBV vaccine
      was observed in the patients with liver steatosis. 93, 7% of serocoversion to
      anty HB-s was observed after vaccination. The GMT of anti- HBs was 97,37 IU/l.
      Patients suffering from liver cirrhosis responded much less favorably to the
      hepatitis B vaccine than patients with liver steatosis. Seroconversion rate after
      third dose was 38,5%only, and GMT of anti-HBs was 18,48 IU/l. CONCLUSION:
      Patients suffering from the liver cirrhosis react much less favorably to the
      hepatitis B vaccine than patients with the liver steatosis.

PMID- 16964671
TI  - [Research results on sensitivity of surveillance on the infectious diseases of
      PSSE Zwolen].
AB  - The aim of the paper was to evaluate sensitivity of surveillance of infectious
      diseases in 2005, in comparison to 2000-2004 (i.e. after taking the measures to
      improve notification of infectious diseases). In the first half of 2005
      significant improvement was noticed, mainly in the group of diseases, which had
      been to be reported obligatorily since 2002 (e.g. helminthiasis). The improvement
      of notification and registration was short-lasting. In the second half of the
      year the drop of notification and registration was reported. There is a need of
      active and permanent monitoring of notification and registration of infectious
      diseases and renewed consideration of the list of diseases which are subjected to
      be obligatorily notified.

PMID- 16964672
TI  - [Leptospirosis laboratory of WSSE in Wroclaw (1947-2005). Comment on its
      activity].
AB  - The article summarises the 1947-2005 activity of the Leptospire Laboratory of
      Voivodeship Sanitary-Epidemiological Station in Wroclaw (1947-2005) which is the
      oldest and, presently, the only health care diagnostic laboratory offering
      leptospirosis testing in Poland. Based on own experience the authors analysed
      laboratory diagnosis of leptospirosis in Poland, identifying existing problems.

PMID- 16964673
TI  - [Hospital acquired pneumonia at the intensive care units. The active nosocomial
      infections surveillance programme of Polish Society of Hospital Infections].
AB  - Currently, the Polish Society of Hospital Infections is coordinating a national
      program of active surveillance of nosocomial infections. One of its elements is
      the control of hospital acquired pneumonia (PNEU) on Intensive Care Units. This
      paper analyzes the epidemiology and etiology of hospital acquired pneumonia
      (PNEU) at the Intensive Care Units (ICU). Surveillance was conducted by means of
      an active method of detection and registration of infections by the Infection
      Control Team (ICT) in cooperation with the unit personnel, in accordance with CDC
      definitions, during the years: 2002-2003 IN 8 Polish ICU -surgical, medical and
      mixed. A total of 11 587 hospitalized patients from ICU were covered by the
      program, with 191 confirmed cases of PNEU. The average cumulative incidence of
      PNEU was 5.6% (median 4.9%), incidence density of Ventilator Associated Pneumonia
      (VAP) on average reached 17.9 per thousand (median 18.8 per thousand); mortality
      of patients with PNEU totaled 12.6% and for patients on ventilator and with
      coexisting infections 15.0% and 20%, respectively--it wasn't high enough to be
      statistically significant. Dominant etiologic factors of hospital acquired
      pneumonia in patients with a risk factor were Pseudomonas aeruginosa and
      Escherichia coli Methicillin-resistant Staphylococcus aureus(MRSA) comprised
      21.1% of isolated S. aureus strains. The analyzes in this paper show that it's
      possible to effectively implement uniform methods of detection, qualification and
      analysis in relatively new settings at Polish hospitals, where tools of modern
      hospital epidemiology are only used since the mid 90-ties.

PMID- 16964674
TI  - [Optimization of the method of treatment of chronic viral hepatitis C with
      pegylated interferon-alfa and ribavirin].
AB  - Despite of significant progress in the treatment of chronic hepatitis C after
      introduction of combination therapy with pegylated form of interferon-a with
      ribavirin, still overall response rate in HCV genotype-1 infected has been
      modest. Several teams has been working on modification of therapeutic methods.
      Optimization of the results is realized by individualization of therapy taking
      under consideration some known virological and host features. The main trends are
      following: settlement of optimal period of treatment of infected with HCV
      genotype-1, applying interferon-induction therapy for non-responders and
      relapsers at the course of previous treatment, as well as prolongation of therapy
      period, and ribavirin-dose increasing. Very important is also looking for optimal
      predictive-viral parameters in early course of disease.

PMID- 16964675
TI  - [Results of 48 weeks lamivudine treatment of patients with chronic hepatitis B
      and HBeAg (-)].
AB  - Lamivudine is an oral nucleoside analogue with strong antiviral activity against
      hepatitis B virus. The HBeAg-negative patients tend to have lower serum HBV viral
      loads when compared to HBeAg-positive patients, but may develop liver disease.
      The objective of this study was to analyse the efficacy of lamivudine treatment
      of chronic hepatitis B patients negative in HBe antigen (HBe-Ag-negative). 102
      patients were treated in Hospital of Infectious Diseases in Warsaw in the years
      2001-2002. Patients were treated for 48 weeks with 100 mg lamivudine once daily
      (50 mg in case of renal failure). The end point of therapy of patients with
      chronic HBV infection negative for e antigen is more difficult to determine than
      for HBeAg-positive patients because HBeAg seroconversion marker cannot be
      applied. The only useful markers of therapy efficiency are the supression of HBV
      DNA replication and normalization ofALT activity level. Results at the end of
      therapy: normalization of ALT activity was observed in 48,7% patients, inhibition
      of viral replication was detected in 65,6% patients. The results are
      comparablewith known randomized clinical trials.

PMID- 16964676
TI  - [Results of 48 weeks lamivudine treatment of patients with chronic hepatitis B
      and HBeAg (+)].
AB  - Chronic hepatitis B is an important public health problem worldwide. In Poland
      the incidence rate decreased from 40,0 (in the year 1990) to 3,86 (in 2004) per
      100,000 inhabitants. The goal of anti-chronic hepatitis B therapy is to prevent
      the progression of liver disease to cirrhosis which may effect in development of
      liver failure or HCC. The aims of treatment are: reduction of HBV viral load and
      normalization of ALT activity. Among HBeAg positive patients important marker is
      the loss of e antigenemia followed by seroconversion to anti-HBe positivity.
      Lamivudine is an oral nucleoside analogue with strong antiviral activity against
      hepatitis B virus. The objective of this study was to analyse the efficacy of
      lamivudine treatment of chronic hepatitis B patients positive for hepatitis B e
      antigen (HBeAg). 224 patients were treated in Hospital of Infectious Diseases in
      Warsaw in the years 2001-2002. Patients were treated for 48 weeks with 100 mg
      lamivudine once daily (50 mg in case of renal failure). Results obtained at the
      end of therapy: loss of HBeAg was observed in 33,4% and seroconversion to anti
      HBe in 15,1% patients, normalization of ALT activity was noticed in 53,4%
      patients, inhibition of HBV DNA replication was observed in 37,9% patients. The
      results are comparable with known randomized clinical trials.

PMID- 16964677
TI  - [The treatment of HCV infection with interferon alpha and ribavirin in a child
      with diabetes I type].
AB  - HCV is a leading cause of chronic hepatitis in worldwide and diabetes is thought
      to be a risk factor of HCV infection. Interferon treatment may induce the
      autoimmune reactions. We report a case of 10 year old girl with diabetes since 4
      th year of life and HCV infection since 9 year of life, treated with alpha
      interferon and ribavirin for 12 months. Interferon was administered in doses of 3
      MU 3 times a week, ribavirin 200 mg 3 times daily. Liver function (ALT, AST, GGT,
      prothrombin) and morphology was monitored every 6 weeks. Autoantibodies (ANA,
      ASMA, AMA, ATG, TPO) were tested before the treatment, after 6 and 12 months of
      the treatment. We have observed the adverse reactions typical for interferon and
      ribavirin treatment, such as: loss of appetite, muscle and joint pains, hair
      loss, emotional lability, concentration disturbance, irritability, somnolence and
      mental depression, which subsided after the end of the treatment. The
      transitional ALT, AST elevation in 6th month of the treatment was observed.
      During the therapy hypothyreosis was diagnosed in the 7th month, and thyroid
      autoantibodies (ATG and TPO) appeared in the 12th month. ANA antibodies were
      present before therapy and its titer increased after 6 month of treatment. During
      the therapy pneumonia, thrombocytopaenia and anaemia were observed in 6th month.
      CONCLUSIONS: diabetes is not contraindication to interferon and ribavirin
      treatment. Interferon treatment in the patients with genetic predisposition to
      thyroid gland diseases and in the patients with present autoantibodies ought to
      be applied with special caution.

PMID- 16964678
TI  - [Brain abscess: analysis of prevalence and clinical course].
AB  - The aim of the study was the analysis of the patients with bacterial meningitis
      and brain abscess who were treated in the Department of Infection Disease and
      Hepatology of Medical University in Lodz in years 1996-2005. We reviewed their
      clinical presentation, bacteriology treatment and outcome retrospectively. Among
      135 patients who were confirmed cases of bacterial meningitis 16 identified as
      having brain abscesses. The prevalence rate of brain abscesses significantly
      increased in years: 2004-2005. The common predisposing factors were otic and
      teeth infections, sinusitis, penetrating head trauma, and bacterial endocarditis.
      Solitary abscess was found in 56% of the cases while in 44% of the cases multiple
      abscess were found. The most common presentation: headache, fever and
      neurological deficit were present in 37% of the cases. 75% of patients were
      disqualified from early neurosurgical intervention and antibiotic therapy were
      recommended. The antibiotic therapy was effective only in 1 patient. The
      mortality rate was 38% and 56% of the survivors had late neurological defects.
      The prevalence rate of brain abscesses significantly increased in years 2004
      2005. Over all mortality was very high and antibiotic therapy hasn't been
      effective treatment in brain abscess at the late stage of its evolution. The
      early neurosurgical intervention is recommended. Late neurosurgical intervention
      strongly influences poor outcome in patients with brain abscess.

PMID- 16964679
TI  - [Influence of intravascular coagulation on brain injury and clinical course in
      purulent meningitis].
AB  - Purulent meningitis (PM), depending on etiology, is associated by up to 30-40 %
      risk of severe neurological complications and death. Neuronal death occurs
      frequently as a result of toxin-induced apoptosis and hypoxia. Hypoxia is the
      result of cerebral edema and hypoperfusion. The former being the reason for, the
      later the result of elevation of intracranial pressure. Hypoperfusion
      additionally results from loss of autoregulation of cerebral perfusion and
      disseminated intravascular coagulation (DIC), causing thrombosis. Spare works in
      human-beings announce a frequency of DIC of ca 40% in PM. The influence of DIC on
      prognosis remains unsatisfactory explained. Uncommon are also reports on use of
      anticoagulants, most often heparins, in PM, but they indicate a possible benefit.
      It is necessary to conduct epidemiological studies evaluating and staging DIC in
      patients with PM as well as multivariate analysis to determine its influence on
      outcome. Drugs of anticoagulant action should be considered for improvement the
      efficacy of supportive therapy, because this could be of benefit for outcome in
      PM.

PMID- 16964680
TI  - [Occurrence of disseminated intravascular coagulation in purulent meningitis and
      influence on mortality in 118 patients].
AB  - Disseminated intravascular coagulation (DIC) is an important, but not
      satisfactory explained risk factor of death in purulent meningitis (PM).
      OBJECTIVE: Evaluation of: 1) acute thrombocytopenia (ATP) in patients with PM, 2)
      dynamics in changes of peripheral blood platelet (PLT) count and serum
      coagulation factors, 3) correlation between acute DIC and mortality in PM.
      METHODS: Analysis ofATP (platelets < or = 150 K/microL and/or decrease in PLT >
      or = 100 K/microL/24 hours) and prothrombin ratio, fibrinogen, d-dimmer and
      antithrombin III in survivors and nonsurvivors in 118 adult patients with PM. 37
      further patients have been disclosed because of non-bacterial PM or chronic
      conditions predisposing to ATP or DIC. MAIN OBSERVATIONS: DIC defined as ATP
      occurred in 56 %, defined as elevated d-dimmer level in 72%. 16 (14%) patients
      died. RESULTS: Mortality correlated significantly with the lowest PLT count on
      first 3. days (p=0,049) and with PLT decline (p=0,015). Differences in
      survivors/nonsurvivors were observed in: ATP on 1. day 48% vs. 75% (p<0,05),
      daily PLT decline 9%/day vs. 32%/day (p<0,05), prothrombin ratio 89% vs. 74%
      (p<0,05) and INR 1,2 vs. 1,7 (p<0,005). CONCLUSION: DIC is an important risk
      factor in PM. Aggravated DIC do correlate significantly with higher risk of
      death.

PMID- 16964681
TI  - [Evaluation of cerebrospinal fluid and plasma lactate dehydrogenase activity in
      patients with purulent, bacterial meningoencephalitis].
AB  - The aim of the study was evaluation of usefulness of cerebrospinal fluid (CSF)
      lactate dehydrogenase (LDH) activity assessment in diagnostics of purulent,
      bacterial meningoencephalitis in adults. The investigations were performed in 17
      subjects. In all individuals CSF and plasma LDH activity was estimated during the
      first 24 hours of hospitalization. Mean CSF LDH activity in patients in very
      severe clinical state (group I) was 299,11 U/L compared to 163,67 U/L in subjects
      of group II with moderate and mild course of disease. The difference between mean
      CSF activities of this enzyme was statistically significant (p<0,001). The
      obtained results indicate the usefulness of CSF LDH activity assessment in
      estimation of severity of the patient's clinical state. The magnitude of this
      activity seems to be also helpful as prognostic marker in purulent, bacterial
      meningoencephalitis.

PMID- 16964682
TI  - [Clinical and laboratory features of mumps in hospitalized children in 2003-2004
      epidemics].
AB  - OBJECTIVES: The frequency and duration of hospitalization as well as symptoms and
      chosen laboratory tests in children with mumps hospitalized during 2003-2004
      epidemics. METHODS: The inpatients records of children with mumps hospitalized
      from January 2003 to September 2004 at the Clinic of Pediatric Infectious
      Diseases in Bialystok were reviewed. RESULTS: At this time, the percentage of
      hospitalizations due to mumps increased from 1.6% up 34.3% in December 2003. The
      main cause of hospitalizations was mumps meningitis (81.4%). Children with mumps
      orchitis (3.4%), pancreatitis (1.9%) and mixed symptomatology i.e. meningitis
      with pancreatitis (2.3%) or meningitis with orchitis (1.1%) were also
      hospitalized. Children with pancreatitis needed the most longer time of
      hospitalization (16 days). The analysis of the laboratory tests revealed that
      serum lipase has the most diagnostic value for mumps pancreatitis and lymphocytic
      pleocytosis for meningitis. CONCLUSION: Mumps-associated morbidity could be
      limited if susceptible children population

PMID- 16964683
TI  - [Cat scratch disease--course, diagnosis].
AB  - Cat scratch disease is an infection which often causes regional lymphadenopathy.
      Bartenolloses present a growing health problem both in human and veterinary
      medicine. They may be etiological fevers of unknown etiology, endocarditis,
      pneumonia, meningitis. The mildest clinical form is the cat scratch disease which
      proceeds as a mild regional lymphadenopathy. It is caused by Bartonellosis
      henselae. Animals, especially cats, are the sourse of infections. Lymphadenitis
      may remain for many weeks and requires differentiation from other causes of
      regional lymphadenopathy. Three typical cases of the disease are presented. All
      sick persons had contact with cats. In none case a primary change was observed.
      In the case no 1 the possibility of occurrence of the disease was not considered
      and it was diagnosed only after histopathological examination of lymphnodes. In
      the two other cases diagnoses were established on the basis of serological
      examination after a few days of admittance for hospital treatment. Cat scratch
      disease is rarely diagnosed in Poland probably due to insufficient knowledge of
      the clinical form of this disease. Swollen lymph nodes together with patient
      contact with a cat or other animals established during a detailed interviewing,
      raise suspicion of CSD. Denial by a patient of the primary change does not rule
      out diagnosis. When regional lymphadenopathy of cat scratch disease is taken into
      consideration in differential diagnosis and serological tests are carried out, it
      may be possible in many cases to eliminate any further diagnostics burdening a
      sick person.

PMID- 16964684
TI  - [Yersinia pestis pathogenesis and diagnostics].
AB  - Plague is an acute bacterial infection caused by Gram negative organism Yersinia
      pestis. This bacteria is subdivided into three classical biotypes: Orientalis,
      Medievalis and Antiqua. Plague is transmitted via flea vectors from rodents to
      humans and by respiratory droplets from animals to humans or humans to humans.
      This agent is on the top of the CDC list of "Critical Biological Agents"-
      category A. It appears to be a good candidate agent for a bioterrorist attack.
      Type III secretion (TTS) is a mechanism by which Y. pestis communicates with
      eukaryotic cells by injecting bacterial proteins across cellular membranes into
      the cytosol of these cells. These bacterial proteins take control of the host
      cells by hijacking their intracellular machinery. A laboratory diagnostics of
      plague is based on: staining techniques, culture on media, immunochromatography,
      hemagglutination, immunofluorescence, ELISA, phage tests and genetical techniques
      including: PCR, multiplex and nested PCR, real time PCR, VNTR, PFGE, ISBF and
      Microarray.

PMID- 16964685
TI  - [Attempt to exclude invasive cardiology services in Poland--rationing, national
      sovereignty and European Union law].
AB  - One of the guiding principles of health policy in many European countries is
      equitable access to health care services. One of the life saving procedures is
      percutaneous transluminal coronary angioplasty (PTCA) performed after coronary
      angiography. Introducing payment for these procedures would limit access for low
      income patients. Fortunately, despite political debate, invasive cardiology
      develops well in Poland. It is important to notice that within the European Union
      Polish citizens would be able to receive this treatment in other member states
      and, according to a European Court of Justice ruling, the costs would have to be
      reimbursed by the National Health Fund. The wider implication is that the 10 new
      EU member states now have to realise that health care is no longer a matter of
      national sovereignty - a fact legislators and health care managers in the 15
      member states of the pre-accession EU are still struggling with.

PMID- 16964686
TI  - [The functional ability and efficiency of motor skills evaluation of individuals
      admitted into nursing homes in Poland].
AB  - The objective of the study was to evaluate the functional ability and efficiency
      of motor skills of Individuals admitted into nursing homes. The study took place
      between the years of 1997-2004 in a group of 122 individuals. The evaluation was
      based on two scales: ADL and IADL. The fall-related injury scale was used to
      evaluate the functionality ability and efficiency of motor skills. The Tinneti
      Scale of fall-related accident risk assessment was used to evaluate the
      functional ability and efficiency of motor skills. The study concluded that a
      majority of the individuals revealed a decrease in their functional ability and
      efficiency of motor skills. This is most relevant to individuals admitted
      directly from hospitals. The organization and development of new nursing home
      facilities must meet the needs of the individuals. The individuals admitted
      directly from the hospital require the best care due to their critical health
      status.

PMID- 16964687
TI  - Prevalence of HBsAg among residents of social assistance homes in Podlaskie
      Province (northeastern Poland).
AB  - Residents of stationary long-term care institutions may be at increased risk for
      hepatitis B virus infection. The study was undertaken to determine the prevalence
      of HBsAg among residents of social assistance homes, to identify risk factors for
      HBV transmission and to assess the need for prevaccination screening for HBV.

PMID- 16964688
TI  - [Thermotolerant Campylobacter occurrence in slaughtering animals].
AB  - The aim of the study was detection and quantification of thermotolerant
      Campylobacter spp. in swab samples taken from carcasses of slaughter animals,
      i.e. poultry, cattle and pig. It has been examined 287 poultry, 176 pork and 114
      beef carcass samples. Additionally, 22 poultry carcasses taken directly from
      slaughter line operation after evisceration were examined on the level of
      Campylobacter spp. contamination. Among the 287 isolates of Campylobacter spp.
      from poultry the most frequent was C. jejuni (59.1%), followed by C. coli (34.2%)
      and C. lari (6.3%). A few isolates strains from pork or beef carcasses were
      classified as C. coli (3.4%) or C. jejuni (0.9%).

PMID- 16964689
TI  - [Epidemiology of congenital malformations in neonates born alive in the Institute
      of Gynecology and Obstetrics of Medical University in Lodz in the years 2001
      2003].
AB  - Institute of Gynaecology and Obstetrics of Medical University in Lodz acceded the
      Polish Register of Congenital Malformations and keeps on propagating the program.
      The aim of the study was to estimate the frequency of congenital malformations in
      newborns delivered in the Institute of Gyneacology and Obstetrics in Lodz in the
      years 2001-2003 and to analyse some epidemiological parameters concerning inborn
      defects in the region of Lodz. The study is based on the retrospective analysis.
      All neonates born alive in our Institute in the years 2001-2003 were taking into
      consideration. The data about inborn malformations was collected from the medical
      documentation and the results were confronted with demographic analysis of the
      region of Lodz. RESULTS: Among 66474 neonates born alive during analysed period
      of time in the region of Lodz, 4507 (6,78%) were delivered in the Institute of
      Gyneacology and Obstetrics in Lodz. There were 106 newborns congenitally
      malformed, so the percentage of inborn defects reached 2,35% of all neonatal
      population. From the region of Lodz 966 babies with inborn malformations were
      notified to the Polish Register of Congenital Malformations, and 106 (10,9%)
      malformed newborns were registered from our Institute. Malformations of heart and
      circulatory system were the most frequent--28,8%, defects of skeletal and
      muscular system were the next -18%, and malformations of urogenital system formed
      16,2%. In the region of Lodz there were 477 neonatal deaths and 121 cases were
      caused by congenital anomalies, which makes the percentage of 25,4% of neonatal
      mortality. CONCLUSION: 1. Congenital malformations are the one of the main
      reasons of neonatal and infantile mortality. 2. The program of registrating
      malformations helps in exact epidemiological analysis of congenital anomalies in
      newborns.

PMID- 16964690
TI  - [The incidence of sexually transmitted diseases among Polish soldiers serving in
      U.N. military forces in the Middle East and south-east Asia].
AB  - The results of own studies concerning the incidence of sexually transmitted
      diseases in the population of Polish soldiers serving in U.N. Military Forces in
      Lebanon (UNIFIL) and Cambodia (UNTAC) are presented in the article. The
      epidemiological analysis was based on the medical documentation of the patients
      treated in UNIFIL Hospital from 1993 to 2000 and in UNTAC medical centers from
      1992 to 1993. The research showed that among the military personnel of U.N. peace
      mission in Lebanon sexually transmitted diseases caused no epidemiological
      problem. On the other hand, venereal diseases in Cambodia made up one of the main
      causes of morbidity in the population of Polish soldiers. The main reason of
      treatment of sexually transmitted diseases in the analyzed period was gonorrhea.

PMID- 16964692
TI  - [Effectiveness of smoking cessation interventions for pregnant women--meta
      analyses of randomized trials and description of the study performed in Poland].
AB  - OBJECTIVES: The aim of the study was to evaluate the effectiveness of smoking
      cessation interventions for pregnant women. DESIGN: The study including meta
      analyses of randomized trials and description of the study performed in Poland.
      MATERIALS AND METHODS: The anti-smoking counseling for pregnant women was
      performed in the maternity centers in Lodz. This study consisted of two stages.
      At the first stage which was performed between 1 December 2000 and 31 December
      2001, 149 current smokers and 56 spontaneous quitters were randomized into the
      smoking cessation intervention and 144 current smokers and 37 spontaneous
      quitters were included into the control group. The intervention program included
      four midwife visits during pregnancy and one after delivery. The control units
      received standard written information about the health risk from maternal smoking
      to the fetus. The second stage of the study included collection of data on
      smoking relapse one year postpartum. RESULTS: The chance of quitting smoking by
      the women who agree to participate in the program was significantly higher in the
      intervention group than in the control group (OR=5.8; p<0.001). The chance to
      maintain smoking abstinence one year after delivery was four times higher in
      intervention than control group (3.7, p=0.03). CONCLUSIONS: The midwife-assisted
      smoking cessation intervention preformed in Lodz region seems to be an effective
      tool to help pregnant smoker make a decision to quit smoking and maintain smoking
      abstinence after delivery.

PMID- 16964691
TI  - [The value of a urine protein-to-creatinine ratio assessment in a single voided
      urine specimen in prediction of 24-hour proteinuria in pregnancy induced
      hypertension].
AB  - OBJECTIVES: Detecting proteinuria is an integral part in management of
      hypertensive pregnant women. The measurement of protein excretion in a 24-hour
      urine collection is used as the gold standard for the diagnosis and follow-up of
      pathologic urinary excretion. However, 24-hour urine collection is time
      consuming, cumbersome and often inaccurate especially during pregnancy. Pregnant
      women find it very inconvenient and difficult. AIM: The study was undertaken to
      validate the prediction of 24-hour protein excretion by a single voided urine
      protein-to-creatinine ratio in hospitalized hypertensive pregnant women. MATERIAL
      AND METHODS: The study was performed in the Pregnancy Pathology Ward, City
      Hospital in Gdynia in 2002-2004. Pregnant women at > or = 20 weeks with
      hypertension (blood pressure > or = 140/90 mmHg) with proteinuria at initial
      urine examination were evaluated. A protein-to-creatinine ratio was obtained from
      first voided urine sample next morning and then urine was collected for next 24
      hours for measurement of protein excretion. RESULTS: 44 women were evaluated. A
      total of 56 cases of the 24-hour urine collection were analyzed. There is a close
      correlation between the protein-to-creatinine ratio in random urine samples and
      the 24-hour protein excretion measured by 24-hour urine collection. Pearson
      correlation coefficient R=0,85 (P<0,001, R2= 0,73). A protein-to-creatinine ratio
      < 0,2 (g/g) can rule out significant proteinuria (defined as 24-hour urinary
      protein excretion > 300 mg) with sensitivity 92,0%, specificity 90,32%, positive
      predictive value 88,46%, negative predictive value 93,33%. CONCLUSIONS: The
      protein-to-creatinine ratio of a single urine sample correlate with the 24-hour
      urine protein excretion. A protein-to-creatinine ratio < 0,2 (g/g) can rule out
      significant proteinuria.

PMID- 16964693
TI  - [The nitric oxide metabolites in women with hypertension in pregnancy].
AB  - OBJECTIVES: Hypertension occurs in 5 to 10 % of pregnancies. As the result we can
      observe the increased percentage of preterm deliveries and cesarean sections.
      Hypertension is well-known reason of intrauterine growth restriction. The
      decrease of nitric oxide metabolites production may be connected to endothelial
      cells deficiency. It depends on NO deficiency and lipid peroxidation processes.
      The concentration of NO metabolites measured in pregnancy can show the
      correlation between oxidative stress and NO metabolism. High risk of destruction
      biological function of cells by free radical processes is observed in
      hypertension DESIGN: The aim of the study was to find correlation between the
      nitric oxide metabolites such nitrites in healthy pregnant women and in
      hypertensive pregnancies. MATERIALS AND METHODS: The study was taken in Medical
      University in Lodz in 2002-2005. The study group consisted of 35 women with
      hypertension in pregnancy, the control group consisted of 30 healthy women. The
      nitrite activity was measured by Oxis kit and was expressed in micromol/l.
      RESULTS: In group of hypertensive pregnancies lower concentration of NO
      metabolites was observed if compared to the control group. CONCLUSIONS: We found
      the difference between two groups and the decrease of NO metabolites
      concentration in hypertensive pregnancy.

PMID- 16964694
TI  - [Lipid peroxidation in women with gestational hypertension complicated by
      asymetric intrauterine growth retardation].
AB  - OBJECTIVES: Hypertension in pregnancy is connected with increased rate of
      prematurity and perinatal morbility. 8-isoprostane and lipid peroxides are the
      oxidative stress indices, similar to the prostaglandins both connected with
      vessels restriction. DESIGN: The aim of the study was to find the correlation
      between concentration of lipid peroxides and 8-isoprostane and the blood pressure
      in pregnancy. MATERIALS AND METHODS: The study was done in Dep. of Obstetrics and
      Gynaecology Medical University in Lodz in 2002-2005. The study group consisted of
      78 women with diagnosed hypertension in pregnancy, the control group of 50
      healthy pregnant women at the same gestational age. Lipid peroxides and 8
      isoprostane were measured in maternal blood. The Oxis Immunoassay for 8-epi
      prostaglandin and LPO 586 were used. The results were expressed in ng/ml and
      microM. RESULTS: The concentration of 8-isoprostane in women with hypertension
      was 0,0691 ng/ml, in women with hypertension and IUGR the value of 8-isoprostane
      was similar--0,0728 ng/ml. In women in normal pregnancy was lower--0,0541 ng/ml.
      Lipid peroxides and 8-isoprostane concentration in both hypertensive groups was
      higher than in group of normotensive pregnant women. CONCLUSIONS: In pregnancies
      complicated by hypertension the concentration of vasorestrictive lipid
      peroxidation products is higher than in normotensive women and the antioxidative
      treatment may be used to decrease lipid peroxidation process.

PMID- 16964695
TI  - [Pregnancy as a risk factor in development of varicose veins in women].
AB  - OBJECTIVES: The purpose of this study was to analyse prevalence of so called
      classical risk factors for VV in patients with this entity. MATERIALS AND
      METHODS: Study consisted of three parts. In the first part the prevalence of risk
      factors in 130 men and 360 women with VV was compared. In the second part the
      prevalence of risk factor in 360 women with VV and 162 without VV was compared.
      In the third part the prevalence of risk factors in pregnant women with and
      without VV was compared. The age of patients in all groups was comparable. The
      results were statistically analyzed. RESULTS: There were no differences in
      prevalence of classical risk factors between men and women with VV. In non
      pregnant women positive family history (OR 2,27, p=0,018) and previous
      pregnancies (OR 2,05, p=0,046) were associated with presence of VV. Premenstrual
      aching of lower extremities and obesity were at the border of statistical
      significance, OR and p, 1,9 and 0,062 and 1,4 and 0,071, respectively. As many as
      47% of pregnant women had VV. Positive family history (OR 2,27, p=0,018),
      previous pregnancies (OR 2,56, p=0,011) and premenstrual aching of lower
      extremities (OR 2,03, p=0,021) were associated with presence of VV. Remaining, so
      called classical risk factors such as oral contraceptive, working in a sitting or
      standing position or constipations were not associated with occurrence of VV.
      CONCLUSIONS: In conclusion, positive family history and previous pregnancies seem
      to be principal risk factors for VV in women.

PMID- 16964696
TI  - [Comparison of gas and gasless laparoscopy in the treatment of benign ovarian
      tumors].
AB  - OBJECTIVES: The aim of the study was to compare the outcomes of the gas and
      gasless laparoscopy in the treatment of benign ovarian tumors. MATERIALS AND
      METHODS: Retrospective analysis of 48 gas and gasless laparoscopic cystectomies
      (24 in each group) performed between 2004-2005 in Holy Family Obstetrics and
      Gynecology Hospital in Warsaw was carried out. An ovarian tumor considered to be
      benign was the indication to operation. All gas laparoscopies and 25% gasless
      laparoscopies were performed under general anesthesia. Remaining 75% gasless
      laparoscopies were performed under epidural anesthesia. RESULTS: The average time
      of gasless laparoscopy was 53 minutes and gas laparoscopy 48 minutes. In all
      cases histopatologic examination during surgery was done. Those assessments
      revealed that all tumors had been benign. The hospitalization time in both groups
      lasted to 72 hours after operation. An average blood loss during the surgery,
      pain felt during the first 24 h after the surgery and the number of complications
      were similar (statistically insignificant) in both groups. CONCLUSIONS: Gasless
      laparoscopic cystectomy is equally efficient and safe as gas laparoscopy. The
      lack of necessity of producing and maintaining pneumoperitoneum during the
      surgery was additional advantage of gasless laparoscopy in comparison to gas
      laparoscopy, because it was possible to perform it in epidural anesthesia.

PMID- 16964697
TI  - [YB-1 protein expression in ovarian cancer].
AB  - OBJECTIVES: Unfavourable prognosis of ovarian cancer is due to prompt
      progression, advanced stage at time of diagnosis and chemoresistance. No protein
      tissue prognosticators of ovarian cancer are in clinical use yet. YB-1 belongs to
      a family of "cold shock proteins" and participates at gene expression control at
      several levels. High expression of YB-1 in tumour tissue correlates with
      unfavourable prognosis and chemoresistance in some malignant neoplasms. THE AIM:
      of this study was to determine the expression of YB-1 in benign and malignant
      ovarian neoplasms and to correlate the expression of YB-1 with clinical
      indicators of cancer progression. METHODS: Specimens of 11 benign ovarian cysts
      and 14 cystadenocarcinomas of the ovary were obtained.YB-1 expression was
      determined by immunohistochemistry. Staging of ovarian cancer was performed
      according to FIGO. RESULTS: Mean YB-1 expression levels in benign and malignant
      tumours were 5.36 +/- 4.1 and 2.86 +/- 4.18 points respectively and were not
      significantly different (p=0.18). No correlation between FIGO stage and
      expression of YB-1 was found in the group of ovarian cancers, either (p=0.32).
      CONCLUSIONS: This study demonstrates that YB-1 is expressed both in benign and
      malignant ovarian tumors. Although there we didn't found any correlation between
      YB-1 expression and FIGO stage, YB-1 could be useful in the prognosis recurrence
      after chemotherapy.

PMID- 16964698
TI  - [Efficacy of burch colposuspension in the stress urinary incontinence treatment
      evaluated with he use of consort diagram].
AB  - Different results of stress urinary incontinence (SUI) treatment may be caused by
      methodological bias. A group of specialists have introduced a new way of clinical
      results analysis, called CONSORT (The Consolidated Standards of Reporting Trial).
      OBJECTIVE: The aim of the study was to evaluate CONSORT diagram usefulness to
      objectivize analysis of effectiveness of operative urinary stress incontinence
      (SUI) treatment with the use of Burch colposuspension. MATERIAL AND METHODS:
      Prospective analysis was provided among 50 women planned for Burch
      colposuspension because of SUI II and III degree. Before treatment and half year
      later there were performed urogynecological exams according to protocol. RESULTS:
      With use of CONSORT diagram we evaluated the percentage of cured patients between
      42% to 70% according to diagnostic method and possibility to obtain complete
      data. CONCLUSIONS: The use of CONSORT diagram allows detailed analysis of data
      completeness. It is useful to minimize the bias effect resulting from lack of
      results of particular exam. It is useful to objectivize estimation of
      effectiveness of SUI treatment with use of Burch colposuspension.

PMID- 16964699
TI  - [Massive fetomaternal hemorrhage--case report].
AB  - Massive fetomaternal hemorrhage is defined as a loss of more than 30-50ml of
      fetal blood, transferred into maternal circulation. It can lead to severe
      anemization of the fetus and its consequences such as fetal hydrops or
      stillbirth. We present a case in which the diagnosis was based on the decresased
      fetal movement and pathological cardiotocography record. The Kleihauer-Betke test
      revealed a high percentage of fetal cells and allowed to state a proper
      diagnosis. An immediate cesarean section was performed and the lab tests
      confirmed severe anemization of the newborn.

PMID- 16964700
TI  - [Iniencephaly in one of the twin--case report].
AB  - Iniencephaly is a rare malformation characterized by the triad of occipital bone
      defect, cervical dysraphism and fixed retroflexion of the fetal head with poor
      prognosis. We present a case one of the twin with iniencephaly and congenital
      heart defect (common atrio-ventricular canal) with normal karyotype.

PMID- 16964701
TI  - [Is MDR 1 gene a key to successful chemotherapy?].
AB  - Pharmacogenetics achievements concerning the problem of multidrug resistance in
      chemotherapy started to be more frequently used in contemporary oncology to
      improve the treatment efficacy by individual approach to the patient. Disturbed
      trans-membrane transport of chemotherapeutics is one of the most important
      mechanisms of chemo-resistance, which seems to depend on the drug resistance
      genes expression (MRP1, LRP, BCRP). Between them, polymorphisms of MDR1 gene
      coding trans-membrane transport glicoprotein P-gp have been reported to affect
      the outcome of therapy, and was studied for different drugs-digoxin,
      fexofenadine, etoposid, vincristine, vinblastine, athracyclines and taxans. It
      seems that genotyping of multidrug resistance genes and identifying specific
      haplotypes can become an important tool in predicting individual sensibility to
      chemotherapy.

PMID- 16964702
TI  - [The role of acupuncture in current perinatology].
AB  - Acupuncture--the old Chinese method of treatment seems to establish its role in
      current medicine including perinatology. There are a lot of symptoms accompanying
      pregnancy that could be diminished by above method. The review summarizes results
      from current literature concerning indications, effectiveness and social
      acceptance of acupuncture in western countries obstetrics.

PMID- 16964703
TI  - Studies on condensed 1,4-dihydropyridine derivatives and their calcium modulatory
      activities.
AB  - Hexahydroquinoline and furoquinoline derivatives were synthesized and their
      calcium modulatory activity was investigated on isolated rat ileum and lamb
      carotid artery. In addition, the in vitro hepatic microsomal biotransformation of
      one hexahydroquinoline derivative was studied in rat microsomes.

PMID- 16964704
TI  - Synthesis, characterization and in situ intestinal absorption of different
      molecular weight scutellarin-PEG conjugates.
AB  - Highly water soluble esters of scutellarin with different molecular weight
      polyethylene glycol (PEG) were synthesized. The physicochemical properties, the
      stabilities under different conditions and the in situ intestinal absorption of
      the conjugates in rats were investigated. By PEG modification, greatly increased
      water solubility and a desirable partition coefficient were obtained. These
      compounds act as prodrugs i.e. breakdown occurrs in a predictable fashion: in
      vitro, the t1/2 of them in PBS buffer at pH 7.4 was above 12 h (37 degrees C),
      while in plasma a more rapid breakdown was observed (t1/2 1.5-3 h). PEGylation
      could enhance the absorption of scutellarin in rat intestine, and scutellarin,
      its PEG conjugates are absorbed through intestine mainly via passive transport.
      When the molecular weight of PEG increased from 200 to 1000 Da, the absorption of
      the conjugates decreased accordingly. The range of PEG molecular weight used for
      the PEGylation of scutellarin was about 400-1000 Da based on considerations of
      the yield, the stability and the absorption.

PMID- 16964705
TI  - New, sensitive and validated spectrofluorimetric method for the estimation of
      etoposide in bulk and pharmaceutical formulations.
AB  - A new, simple and sensitive spectrofluorimetric method was developed for the
      routine estimation of etoposide, an anticancer drug, in bulk and in
      pharmaceutical formulations. The medium selected for the estimation of etoposide
      was methanol : phosphate buffer (pH 7.4) in a ratio of 70 : 30 v/v. Excitation
      and emission wavelengths used were 240 and 324 nm respectively. The method was
      validated according to ICH and U.S.P guidelines. Linearity range was 200-1000
      ng/ml with detection and quantitation limits of 23 ng/ml and 72 ng/ml
      respectively. Regression equation obtained was Fluorescence Intensity = 6.704
      (Concentration in ng/ml) + 115.4. The drug was found to be stable and there was
      no interference from the excipients present in different formulations of
      etoposide.

PMID- 16964706
TI  - Relationship between vasorelaxation of flavonoids and their retention index in RP
      HPLC.
AB  - In the present study the relationship between the vasodilation of flavonoids and
      their retention index (RI) was investigated. Retention index (RI) values of 18
      flavonoids, including flavones, flavonols, flavanones, flavanols and isoflavones
      were measured by an RP-HPLC method based on alkan-2-ones. Vasorelaxation of the
      flavonoids was measured by measuring the reduction in tension by flavonoids in
      rat thoracic aorta precontracted by phenylephrine (PE, 10(-6) mol/L). The results
      demonstrated that the potency of the vasorelaxation of flavonoids was positive by
      correlated with RI. The regression equation was Rex 11.68 + 0.11 RI (n = 18, r =
      0.915, P < 0.01).

PMID- 16964707
TI  - The use of chitosan modified with glutaraldehyde and glyoxal as chromatographic
      support for the separation of flavonoids from Aleurites moluccana leaves.
AB  - This paper describes the preparation of chitosan modified with dialdehydes,
      glutaraldehyde (CH-Glu) and glyoxal (CH-Gly) and its application in the isolation
      of the flavonoids swertisin and 2"-O-rhamnosylswertisin from A. mollucana. The
      additional non-polar alkyl groups increase the hydrophobicity of the sorbent. The
      results show that the separation was mediated by hydrophobic interaction (CH
      Glu), as well as hydrogen bonding, between phenolic OH or rhamnosil residues from
      the flavonoids, and the free amine groups (CH-Gly).

PMID- 16964708
TI  - Rapid in vivo dissolution of ketoprofen: implications on the biopharmaceutics
      classification system.
AB  - The aim of this paper was to investigate the in vivo dissolution behavior of
      ketoprofen, a Class II drug according to the Biopharmaceutics Classification
      System (BCS), in the upper small intestine of dogs. An intubations method was
      used, where no blocking balloons were used to prevent luminal drug transport
      along the GI tract. Our design allowed the drug to be transported freely to more
      distal parts of the GI tract and also, it was supported by a pharmacokinetic
      study. Pharmacokinetic parameters of ketoprofen were determined in dogs after
      administering approximately 0.27 mg kg(-1) (solution) or approximately 1.47 mg
      kg(-1) (suspension) in oral bolus doses. There were not statistical significant
      differences in plasma concentrations for both formulations, either in the maximum
      concentrations C(max) or AUC following oral dose administration. The rapid
      disappearance of ketoprofen from the intestinal lumen, reflected by low mass
      recovery in the supernatant and sediment of the collected intestinal fluid
      samples, in comparison to that recovery of the non-absorbable marker phenol red,
      suggests that ketoprofen is emptying into the small intestine and is rapidly
      dissolved and absorbed. In this study, the in vivo results clearly show that the
      absorption rate of ketoprofen is not dissolution limited; therefore ketoprofen
      would be essentially equivalent to Class I drugs and could be considered for
      waiver of bioavailability and bioequivalence testing.

PMID- 16964709
TI  - Influence of rapeseed phospholipids on ibuprofen dissolution from solid
      dispersions.
AB  - The dissolution profiles of ibuprofen (IB) from solid dispersions prepared by the
      solvent evaporation method, containing the rapeseed lecithin ethanol soluble
      fraction (LESF) or rapeseed phosphatidylcholine (RPC) have been determined. The
      effect of incorporation of PEG 4,000 or PEG 8,000 in the solid dispersions on the
      controlled-release of IB was also investigated. Dissolution studies conducted in
      double-distilled water using the paddle dissolution apparatus showed that the
      initial dissolution rate (IDR) within the first 5 min and the maximum percent of
      dissolved IB of IB/LESF were double of those of IB/RPC (both in ratio 4:1 w/w).
      The low amounts of LESF markedly increased dissolution of IB. Increasing of LESF
      concentration from 0 to 10 and 20% in solid dispersions produced 60 and 100%
      improvement of IB maximum dissolution level respectively, to compare with that of
      IB alone. PEG 4,000 caused the slightly decreasing in IB dissolution rate, while
      PEG 8,000 markedly improved the dissolution of IB in examined conditions.

PMID- 16964710
TI  - Enhancement of dissolution of cyclosporine A using solid dispersions with
      polyoxyethylene (40) stearate.
AB  - A solid dispersion containing cyclosporine A (CyA) and polyoxyethylene (40)
      stearate (PS) was prepared by the solvent-melt method and characterized by powder
      X-ray diffraction (PXRD), hot-stage microscopy (HSM), scanning electron
      microscopy (SEM) and dissolution studies. The crystalline peaks of CyA
      disappeared in the PXRD spectra of solid dispersions but were seen in those of
      physical mixtures, demonstrating the amorphous state of the drug in solid
      dispersions. The solubility of CyA in aqueous solutions of PS was increased
      linearly with increasing amount of PS in water. Dissolution of the drug from
      solid dispersions and physical mixtures was dramatically enhanced compared to the
      drug powder alone in water at 37 degrees C.

PMID- 16964711
TI  - Preparation and targeted delivery of immunoliposomes bearing poly(ethylene
      glycol)-coupled humanized anti-hepatoma disulfide-stabilized Fv (hdsFv25) in
      vitro.
AB  - Peptides in bee venom (PBV) have attracted considerable attention for anti-cancer
      therapy. In this study, sterically stabilized liposomal PBV (PBV-SL) was prepared
      using Soybean phosphatidylcholine, cholesterol, and the cholesterol derivatives
      of PEG with terminal COOH groups. The humanized anti-hepatoma disulfide
      stabilized Fv (hdsFv25) was coupled to sterically stabilized liposomes. The
      hdsFv25-immunoliposome has strong affinity and specificity to SMMC-7721 cells in
      vitro. PBV-loaded sterically stabilized liposomes modified with the hdsFv25 can
      kill SMMC-7721 cells in vitro with higher efficiency than non-targeted liposomes.
      These results demonstrate that this strategy should also be applicable to
      immunotherapy for other cancers.

PMID- 16964712
TI  - On the dilution behaviour of immuno-stimulating complexes (ISCOMs).
AB  - Immunostimulating complexes (ISCOMs) are used as potent vaccine delivery systems.
      However, the mechanisms by which ISCOMs work are mostly unknown. The
      immunological potency of ISCOMs has often been associated with their
      characteristic cage-like structure. Since ISCOMs can be regarded as composite
      mixed micelles that contain Quillaja saponin as the surfactant, we postulated a
      micelle to vesicle transition of the particles upon dilution with aqueous
      solutions. The dilution behaviour of ISCOMs is not only an important preparative
      aspect, but may also be of high relevance for both cell culture and in vivo
      applications in which dilutions occur. Crude and purified preparations of ISCOM
      matrices were prepared by dialysis. Methods used to analyse the micelle to
      vesicle transitions were transmission electron microscopy and dynamic light
      scattering. Significant morphological changes occurred upon dilution with TRIS
      buffered saline and non-buffered saline, and a step-wise transition from the
      typical cage-like structure via both less well defined ISCOM-like structures and
      helical micelles to small lipidic particles was observed. Aggregation of the
      resulting small lipidic particles was noted. The results obtained by dynamic
      light scattering complemented these findings. With increasing dilution factors,
      increase in particle size and polydispersity was observed. Zeta-potentials showed
      a trend towards less negative values upon dilution, indicating that saponins were
      not retained within the lipid matrix. The results indicated that at least partial
      separation of Quillaja saponins from the remaining colloidal species occurred
      upon dilution with aqueous solutions. The release of saponins upon dilution may
      be an important aspect of how ISCOMs work.

PMID- 16964713
TI  - Solubility and stability of curcumin in solutions containing alginate and other
      viscosity modifying macromolecules. Studies of curcumin and curcuminoids. XXX.
AB  - The solubility, chemical- and photochemical stability of curcumin in aqueous
      solutions containing alginate, gelatin or other viscosity modifying
      macromolecules have been investigated in order to obtain an alternative to the
      use of surfactants or cyclodextrins. The solubility of curcumin in aqueous
      solution at pH 5 increased by a factor > or = 10(4) in the presence of 0.5% (w/v)
      alginate (various qualities) or gelatin compared to plain buffer, while propylene
      glycol alginate ester, cesapectin and sodium carboxymethyl cellulose did not have
      a similar solubilizing effect. The solubilization was slightly influenced by pH,
      ionic strength and type and concentration of buffer salts. The macromolecules do,
      however, not stabilize towards hydrolytic- or photolytic degradation of curcumin.

PMID- 16964714
TI  - Stability of oral liquid preparations of methylergometrine.
AB  - The stability of an oral ready to-use form of methylergometrine (0.05 mg/mL),
      which provides a convenient volume for administration (5 mL), was evaluated over
      a forty-seven-day period at different temperatures (5 degrees C and room
      temperature) without light in order to assign a shelf life. Methylergometrine was
      assayed by a stability-indicating HPLC method with diode array detection. The
      drug undergoes degradation under basic conditions and dry heat (50 degrees C).
      All the peaks of the degraded product were resolved from the standard drug with
      significantly different retention times. Statistical analysis proves that the
      method is reproducible and accurate for estimation of the intact drug. The pH of
      samples was monitored periodically for changes. Samples were also visually
      inspected for any colour change, precipitation or crystallization. At least, 96%
      of the initial methylergometrine concentration remained throughout the 47-day
      study period. Over the test period, no significant change was observed in the pH
      or colour of any of the samples. No degradation products were revealed. This
      study allowed an oral ready to use solution of methylergometrine (0.05 mg/ml) to
      be prepared, with a shelf life of more than one month (47 days) when stored at
      room temperature without light.

PMID- 16964715
TI  - Chemotactic activity of serum obtained from patients with idiopathic dilated
      cardiomyopathy.
AB  - Elevated circulating levels of alpha- and beta-chemokines in heart failure have
      been reported. The objective of this study was to investigate the interrelation
      of chemotactic activity of serum and circulating chemokine levels in patients
      suffering from idiopathic dilated cardiomyopathy (IDCM). Chemokine serum levels
      (MCP-1, MIP1-alpha, RANTES, IL-8 and TNF-alpha) were determined in patients with
      IDCM (n = 10), patients with coronary artery disease with normal (CAD-1; n = 10)
      or depressed (CAD-2; n = 10) left ventricular function and healthy controls (n =
      10). The chemotactic effect of sera obtained from these groups was measured using
      an in vitro chemotaxis assay. Sera obtained from IDCM (5475 +/- 681 cells) showed
      the highest chemotactic activity when compared to controls (1850 +/- 215 cells),
      CAD-1 (3325 +/- 275 cells) and CAD-2 (2800 +/- 275 cells, P < 0.05) associated
      with significantly higher circulating MCP-1 levels. Sera obtained from IDCM
      patients show a high chemotactic activity associated with significantly elevated
      circulating MCP-1.

PMID- 16964716
TI  - Trichostatin A improves the anticancer activity of low concentrations of curcumin
      in human leukemia cells.
AB  - Curcumin (Cur), a promising anticancer drug, kills tumor cells through either
      diminishing or promoting reactive oxygen species (ROS) generation. In this study,
      it was investigated whether trichostatin A (TSA), a specific histone deacetylase
      (HDAC) inhibitor and a new anticancer drug, could improve the anticancer activity
      of low concentrations of Cur in human leukemia cells (HL-60). HL-60 cells were
      treated with Cur, TSA or their combinations; cell proliferation arrest, lactate
      dehydrogenase (LDH) release and cell viability were measured as indicators of
      cell damage. Reactive oxygen species (ROS) accumulation and the acetylation of
      histones were also measured. The cytotoxicity of Cur and TSA increased in a time
      and dose-dependent manner. Low Cur (no more than 20 microM) diminished the ROS
      generation in HL-60 cells, while high Cur (50 and 100 microM) promoted that. In
      contrast, TSA showed no influence on ROS generation. When their effects on
      histone acetylation were determined, low Cur showed no effect, while TSA
      significantly increased that. As expected, combinations of low Cur and TSA could
      not only diminish ROS generation, but also increase histone acetylation, and
      hence showed a more significant cytotoxicity in HL-60 cells. Since the extra ROS
      generation may also harm normal cells, instead of using high Cur, combining low
      Cur with TSA is obviously a better strategy to improve the anticancer activity of
      Cur.

PMID- 16964717
TI  - Inhibition of viral proteases by Zingiberaceae extracts and flavones isolated
      from Kaempferia parviflora.
AB  - In order to identify novel lead compounds with antiviral effect, methanol and
      aqueous extracts of eight medicinal plants in the Zingiberaceae family were
      screened for inhibition of proteases from human immunodeficiency virus type 1
      (HIV-1), hepatitis C virus (HCV) and human cytomegalovirus (HCMV). In general,
      the methanol extracts inhibited the enzymes more effectively than the aqueous
      extracts. HIV-1 protease was strongly inhibited by the methanol extract of
      Alpinia galanga. This extract also inhibited HCV and HCMV proteases, but to a
      lower degree. HCV protease was most efficiently inhibited by the extracts from
      Zingiber officinale, with little difference between the aqueous and the methanol
      extracts. Many of the methanol extracts inhibited HCMV protease, but the aqueous
      extracts showed weak inhibition. In a first endeavor to identify the active
      constituents, eight flavones were isolated from the black rhizomes of Kaempferia
      parviflora. The most effective inhibitors, 5-hydroxy-7-methoxyflavone and 5,7
      dimethoxyflavone, inhibited HIV-1 protease with IC50 values of 19 microM.
      Moreover, 5-hydroxy-3,7-dimethoxyflavone inhibited HCV protease and HCMV protease
      with IC50 values of 190 and 250 microM, respectively.

PMID- 16964718
TI  - In vitro prostate cancer cell growth inhibition by Brazilian plant extracts.
AB  - In the present study, 1220 plant extracts obtained from 352 plants belonging to
      73 families that grow in the Amazon and Atlantic rain forests were screened for
      cytotoxicity against PC-3 prostate cancer cell lines. Extracts were tested in the
      single dose of 100 microg/mL. Activity was observed in 17 aqueous or organic
      extracts belonging to Annonaceae, Apocynaceae, Araceae, Capparaceae,
      Commelinaceae, Flacourtiaceae, Lecythidaceae, Leguminosae, Passifloraceae,
      Rutaceae, and Violaceae.

PMID- 16964719
TI  - Antidiabetic activity of an ethanol extract obtained from the stem bark of
      Psidium guajava (Myrtaceae).
AB  - This study analyzed the antidiabetic properties of an ethanol extract of the stem
      bark of Psidium guajava, an indigenous medicinal plant used to control diabetes
      in Indian System of Medicine. The anti-hyperglycaemic activity of this plant on
      blood glucose levels of normal, normal glucose loaded (OGTT) and alloxan-induced
      hyperglycaemic rats was evaluated. The results showed that ethanol stem bark
      extract exhibited statistically significant hypoglycaemic activity in alloxan
      induced hyperglycaemic rats but was devoid of significant hypoglycaemic effect in
      normal and normal glucose loaded rats (OGTT).

PMID- 16964720
TI  - New compounds from Commiphora myrrha (Nees) Engl.
AB  - Phytochemical investigation of Commiphora myrrha (Nees) Engl. has afforded six
      new compounds identified as cadina-3-en-15-ol (myrracadinol A) (1), 7, 8-seco-2,
      5-dihydroxy-12-acetoxycalam-8-ene (myrracalamene A) (2), 7, 8-seco-2, 3, 5
      hydroxy-12-acetoxycalame-8-ene (myrracalamene B) (3), 7, 8-seco-cadin-3, 8-dien
      2beta, 12-diol (myrracadinol B) (4), 7, 8-seco-12-hydroxycalam-8-ene
      (myrracalamene C) (6), 7, 8-seco-cadin-3,7(12)-dien-5alpha,10alpha-diol
      (myrracadinol C) (7) along with a known compound tria-cont-1-ene (5). Their
      structures were elucidated on the basis of spectral and chemical analyses.

PMID- 16964721
TI  - Mystery solved? Benes with multiple conditions to blame for skyrocketing Medicare
      spending.

PMID- 16964722
TI  - What is EHR certification?

PMID- 16964723
TI  - E&M services.

PMID- 16964724
TI  - Do the math: my EHR pays off.

PMID- 16964725
TI  - Do your staff salaries measure up?

PMID- 16964726
TI  - Will this stark workaround work?

PMID- 16964727
TI  - Sometimes, we're family.

PMID- 16964729
TI  - Surveying former patients.

PMID- 16964728
TI  - Is your practice running on empty?

PMID- 16964730
TI  - Med students? Bring them on!

PMID- 16964731
TI  - The easy way to a paperless office.

PMID- 16964732
TI  - When I follow up, I don't give up.

PMID- 16964733
TI  - Pharmacy flu shots hurt doctors.

PMID- 16964734
TI  - Sued? You may never get your day in court.

PMID- 16964735
TI  - Court to insurer: you lose.

PMID- 16964736
TI  - Take "frivolous" suits seriously.

PMID- 16964737
TI  - Sound attenuation from earmuffs and earplugs in combination: maximum benefits vs.
      missed information.
AB  - INTRODUCTION: Noise levels from military aircraft range from 100-130 dBA. Peak
      pressure levels from large caliber weapons may reach 180 dB SPL. To protect
      against hearing loss, individuals are encouraged to wear double hearing
      protection. This study determined ways to maximize benefit. METHOD: Hearing
      thresholds from 0.25-8 kHz and consonant discrimination were assessed in normal
      hearing subjects with ears unoccluded and fitted with highly rated earmuffs and
      earplugs, singly or in combination. The earplugs were available in two sizes.
      Selection was based on best fit. Attenuation values were derived from the
      threshold measurements. RESULTS: With the muff, plug, and muff and plug in
      combination, thresholds ranged from 35-48 dB SPL, 40-55 dB SPL, and 44-66 dB SPL,
      respectively, across the frequencies tested. The combination (without regard to
      size of plug) resulted in attenuation values of 38-54 dB. With the smaller of the
      two plugs, low-frequency values as high as 53-61 dB were realized. Consonant
      discrimination decreased by 6-8% with the devices worn singly and by 22% with the
      devices in combination, relative to unoccluded listening. DISCUSSION: Sufficient
      low-frequency attenuation may be achieved with muffs and plugs in combination to
      prevent hearing loss from operational noise. Attenuation may be maximized by
      choosing a smaller earplug to achieve a better fit. Possible downsides are
      reduced detection of warning sounds and speech intelligibility. To be heard
      warning sounds should surpass protected thresholds by at least 5 dB. Choosing
      devices which provide somewhat less attenuation may be necessary to preserve
      communication capability.

PMID- 16964738
TI  - Post-dive bubble formation in rats: effects of exercise 24 h ahead repeated 30
      min before the dive.
AB  - INTRODUCTION: Recent studies have shown that a nitric oxide releasing agent or a
      single bout of high-intensity exercise 20-24 h before a dive can prevent bubble
      formation following decompression. The aim of this study was to determine whether
      high-intensity exercise immediately prior to a dive eliminates the protective
      effect of a single bout of high-intensity exercise 24 h before the dive. METHODS:
      Twelve female Sprague-Dawley rats were randomly divided into two equal groups.
      Group 1 performed 90 min of exercise twice, beginning 24.5 h and again 2.0 h
      before compression. Group 2 performed 90 min of exercise beginning at 25.5 h
      before compression. The standardized exercise protocol was 7 x 8 min at 85-90%
      maximal oxygen uptake (Vo2max) followed by 2 min at 50% Vo2max for a total of 90
      min including a 20 min warm-up at 40-50% of Vo2max. All rats were exposed to a
      pressure of 700 kPa (7 ATA) for 45 min in a dry hyperbaric chamber followed by
      decompression to the surface at 100 kPa (1 ATA) at a rate of 50 kPa x min(-1)
      (0.5 atm x min(-1)) breathing air. RESULTS: Bubble formation was significantly
      higher in rats that had exercised 24 h and 30 min prior to dive than rats that
      had only exercised 24 h prior to the dive (median bubble grade 4.5 vs. 0.5).
      CONCLUSION: This study demonstrated that acute exercise prior to a dive
      eliminated the protection against bubble formation found 24 h after high
      intensity exercise in rats.

PMID- 16964739
TI  - Motion sickness provoked by torso rotation predicts that caused by head nodding.
AB  - INTRODUCTION: Some degree of space motion sickness is experienced by at least 50%
      of astronauts early in flight. It is unpleasant and could be hazardous during an
      extravehicular activity or urgent re-entry in the first few days after launch. To
      date, there is no reliable ground-based test to predict who will be affected.
      METHODS: Head nodding (HN) in a supine position was used as a model of motion
      sickness caused by an unusual gravito-inertial environment. Torso rotation (TR)
      was used as a means of predicting susceptibility to development of symptoms
      caused by HN. Motion sickness was quantified in 26 subjects (5 men, 21 women, age
      range 18-52) using numerical estimates of discomfort and a more detailed
      questionnaire. Susceptibility to TR and HN was determined on three occasions for
      each stimulus, with test sessions at least 1 mo apart. RESULTS: Subjects reached
      their stopping point at a mean duration of 13.72 min +/- 1.06 CI) for TR and
      11.31 min (+/- 0.38 CI) for HN. When susceptibility to HN was plotted as a
      function of susceptibility to TR and a linear regression line was added, the
      correlation coefficient was 0.744. DISCUSSION: Susceptibility to TR predicts
      susceptibility to HN. The method may be useful as a screening test for potential
      astronauts.

PMID- 16964740
TI  - Heart rate variability during high ambient heat exposure.
AB  - INTRODUCTION: This study observed heart rate variability (HRV) measured in order
      to detect the changes in sympathovagal activity during high ambient (74 degrees
      C) temperature. HRV is a measure of heart rate (HR) fluctuations around the mean
      HR and has been used to indicate the balance between parasympathetic and
      sympathetic function of the autonomic nervous system in medicine and exercise,
      but not in extreme environments. METHODS: There were 10 healthy male subjects who
      wore Polar HR monitors (PE 5000) during a 15-min exposure (74.3 +/- 5.9 degrees
      C). RESULTS: HR increased significantly (p < 0.05) from 66.5 bpm pre-exposure to
      106.0 bpm during exposure to the dry heat. A significant decrease in
      parasympathetic drive was indicated by: (1) a reduction of 89.1 +/- 31.3% in the
      proportion of interval differences between two normal R-R intervals that were in
      excess of 50 ms in length (pNN50); (2) an 83.4 +/- 7.0% decrease in the root mean
      square of successive R-R differences (RMSSD); and (3) an 82.7 +/- 11.4% decrease
      in the normalized high-frequency (HF norm) values. An increase in a sympathetic
      drive was indicated by a significant increase in: (1) the normalized low
      frequency (LF norm) values of (84.5 +/- 19.4%); and (2) the LF:HF ratio (10.9 +/-
      10.8%). DISCUSSION: The results from this study show that exposure to high
      ambient temperature produces a significant increase in HR through an increase in
      sympathetic and decrease in parasympathetic drive.

PMID- 16964741
TI  - Carotid sinus pressure changes during push-pull maneuvers.
AB  - INTRODUCTION: The push-pull maneuver (PPM) is defined as a reduction in G
      tolerance when positive acceleration (+Gz) immediately follows negative
      acceleration (-Gz) exposure, with the carotid baroreceptors presumably playing a
      dominant role in the ensuing BP (SBP) responses. The objective of this study was
      to determine whether application of neck pressure (NP) during the preceding -Gz
      phase maintains +Gz tolerance during subsequent +Gz. METHODS: There were 10
      experienced men who were exposed to 3 centrifuge run types using a multi-axis
      centrifuge: a relaxed control run from +1.4 baseline to visual tolerance; a
      relaxed control PPM run (PPM-C) consisting of 5 s of -1 Gz followed by 15 s of
      +Gz to visual tolerance; and an experimental PPM run performed with pressurized
      neck (PPM-NP) consisting of -1 Gz for 5 s followed by 15 s of +Gz at the previous
      PPM-C G-tolerance level. RESULTS: Relaxed control G tolerance (3.6 _ 0.26 Gz) was
      greater vs. the PPM-C (3.0 +/- 0.21 Gz) and PPM-NP (3.1 +/- 0.20 Gz) conditions,
      but the two PPM conditions did not differ significantly. During -Gz, mean R-R
      interval for PPM-NP was significantly shorter than in the PPM-C from second 1 to
      second 3. During the +Gz phase, however, R-R interval responses between PPM-C and
      PPM-NP differed only at seconds 8 and 9. There were no differences in carotid
      sinus SBP between PPM-C and PPM-NP during -Gr. During +Gz, carotid sinus SBP was
      significantly depressed in PPM-NP and PPM-C conditions vs. Control. DISCUSSION:
      Application of NP during the -Gz phase, despite altering R-R interval, did not
      ameliorate SBP responses or reductions in G tolerance during subsequent +Gz
      exposure. Despite neck compression counteracting increased carotid hydrostatic
      pressure during -Gz, the carotid baroreceptor response is likely opposed by the
      aortic or other baroreceptors.

PMID- 16964742
TI  - Cognition during sustained operations: comparison of a laboratory simulation to
      field studies.
AB  - INTRODUCTION: Military operations, especially combat, expose individuals to
      multiple stressors, including sleep loss, food deprivation, and sustained
      physical activity. Civilians, such as woodland firefighters, disaster victims,
      and relief workers, are also exposed to such environments. Our laboratory
      developed a brief, intense, laboratory-based simulation of a multistressor
      environment which included sleep loss, continuous physical activity, and food
      deprivation. METHODS: During this sustained operations (SUSOPS) scenario, and a
      control period, cognitive performance and mood were measured in 13 volunteers.
      The scenario included road marches, battle drills, and land navigation. Physical
      activity and sleep were assessed with actigraphs. RESULTS: Significant decrements
      in visual vigilance, choice reaction time, and matching-to-sample, a test of
      short-term memory, were observed. Marksmanship was stable and physical activity
      significantly increased. Mood states assessed by the Profile of Mood States
      (POMS: Tension, Depression, Anger, Vigor, Fatigue and Confusion) also
      significantly deteriorated. DISCUSSION: Cognitive function declined more
      extensively and rapidly than physical performance. Decrements in cognitive
      performance were comparable to those in a field study conducted for an equivalent
      period of time in uncontrolled conditions. This demonstrates that decrements in
      cognitive function and increased physical activity, similar to those in highly
      stressful field environments, can be duplicated under controlled conditions. The
      simulated SUSOPS scenario is an appropriate paradigm for assessment of adverse
      effects of military and civilian multistressor environments on human performance,
      physiology, and interventions designed to mitigate them.

PMID- 16964743
TI  - Survivability and injuries from use of rocket-assisted ejection seats: analysis
      of 232 cases.
AB  - INTRODUCTION: Ejection injury has been documented with respect to non-rocket
      assisted seats, but there is little information on injuries associated with
      rocket-assisted seats. This study analyses the survivability of military
      accidents and the injuries associated with rocket-assisted ejection. METHODS: A
      total of 232 Royal Air Force accident reports were accessed and aircrews'
      injuries were related to the aircraft parameters of ejection, aircrew
      anthropometry, and the ejection seat and parachute dynamics. Ejection sequences
      were simulated using a computerized modeling tool to provide information relating
      to the dynamic response index, acceleration of the ejection seats, and
      performance of the parachutes. RESULTS: Ejection survival was 89.2% overall,
      95.7% for within envelope ejections and 23.8% for out of envelope ejections.
      There were 29.4% of aircrew who sustained spinal fractures. Another 14.2% of
      aircrew sustained a head injury and the incidence of head injury in Tornado
      ejectees was higher than the other aircraft types. Compared with 5.8% of ejectees
      from aircraft with an arm restraint system, 11.2% of aircrew sustained upper limb
      flail injuries from ejecting from aircraft without an arm restraint system. Arm
      flail injuries occurred at a higher aircraft speed at ejection compared with
      ejections where no arm flail injuries were sustained. There was also 18% of
      aircrew who sustained lower limb parachute landing injuries. DISCUSSION:
      Information from this study has lead to a redesign of the Tornado ejection seat
      headbox, an improvement in the Tornado ejection catapult dynamics, an upgrade of
      escape system parachutes, and provided evidence that future aircraft should be
      fitted with an arm restraint system.

PMID- 16964744
TI  - Artefactual contraction band necrosis of the myocardium in fatal air crashes.
AB  - BACKGROUND: The detection of conditions associated with possible medical
      incapacitation is a crucial component of the aviation autopsy. Acute myocardial
      ischemia is notoriously difficult to diagnose at autopsy, although various
      pathological markers may strongly support a diagnosis of acute myocardial
      infarction occurring just prior to the crash. HYPOTHESIS: Contraction band
      necrosis may not be a reliable indicator of acute myocardial ischemia in aircraft
      crashes because of the forces on myocardial tissue sustained in the crash.
      METHODS: Microscopic examination of the myocardium of fatal air crash occupants
      was compared with a control group of suicidal hanging deaths. This study examined
      80 air crash fatalities and 44 age and sex matched suicidal ligature hanging
      controls. We assessed both the presence and extent of contraction band necrosis
      type lesions in both groups and scored the lesions. RESULTS: Contraction band
      lesions were seen in the left ventricular myocardium of all study groups. There
      was no significant difference between the contraction band score for crash victim
      deaths and hanging deaths. However, widespread contraction banding was
      significantly more common in air crash victims (p = 0.032). There was no
      significant difference between contraction banding in victims of impacts without
      a post-crash fire compared with those in crashes with a post-crash fire.
      CONCLUSIONS: Contraction band necrosis-like lesions in isolation should not be
      considered as evidence of acute myocardial ischemia in cases of massive trauma.
      Severe trauma, possibly as a result of sudden stretching of the cardiac myocytes,
      may cause a microscopic lesion which is indistinguishable from contraction band
      necrosis.

PMID- 16964745
TI  - Ultralight aviation accident factors and latent failures: a 66-case study.
AB  - INTRODUCTION: Little research has been done on ultralight aviation accidents. A
      better understanding of accident factors allows for better development of
      preventive measures. This study analyzes ultralight accidents with respect to
      significant factors related to active and latent failures, as referred to in
      Reason's Swiss cheese model of human error. METHODS: There were 66 National
      Transportation Safety Board (NTSB) ultralight accident reports that were examined
      from 1985-2004. Contextual information about active and latent failures was
      identified, compiled, and cross-referenced with pilot, aircraft, and accident
      information for evidence of significant relationships. RESULTS: Pilots with less
      than 40 make/model-specific flying hours were significantly more likely to crash
      fatally (chi2 = 9.07; p < 0.005; df=1) than other pilots and/or because of losing
      control (chi2 = 7.24; p < 0.05; df=1) than other accident causes. In contrast,
      pilots with 40 or more make/model-specific flying hours were significantly more
      likely to crash as a result of engine failure (chi2 = 9.33; p < 0.005; df = 1).
      Loss of control as an active failure was usually associated with such latent
      failures as strong winds and insufficient mission planning, while the engine
      failure accidents involved inadequate maintenance. CONCLUSION: In order to reduce
      accident prevalence, ultralight self-regulation organizations should focus on
      training in mission planning, aircraft familiarity, and proper maintenance
      procedures. Further research should concentrate on explaining the prevalence of
      the active and latent failures shown here and determining the effects of the
      FAA's new light sport aircraft category.

PMID- 16964746
TI  - Accelerometry as a measure of subject compliance in unilateral lower limb
      suspension.
AB  - INTRODUCTION: Human unilateral lower limb suspension (ULLS) is a commonly used
      model to study the effects of disuse and unweighting of human skeletal muscle.
      ULLS requires subjects to ambulate on crutches with an elevated shoe on the
      weight-bearing limb or a strap on the unloaded limb for prolonged periods of time
      (i.e., 4-5 wk). Ensuring compliance during ULLS participation is critical to the
      integrity of the study. PURPOSE: The purpose of this study was to determine the
      accuracy of an accelerometer to detect steps taken while walking and to measure
      the effectiveness of an accelerometer to monitor compliance during ULLS. METHODS:
      There were 10 subjects (26.2 +/- 3.6 yr; 170.9 +/- 6.9 cm; 68.0 +/- 9.6 kg) who
      participated in two conditions: normal walking and ULLS (left leg was unweighted
      via an elevated shoe on the contralateral limb) at various speeds. Additionally,
      subjects completed an obstacle course to simulate daily activities. During these
      activities, subjects wore a planar accelerometer on their left ankle to measure
      acceleration. The mean peak axial acceleration (MPAA) of the leg in the swing
      phase of walking was determined by the accelerometer and a step was detected
      during ULLS if the MPAA was greater than or equal to the minimum MPAA observed
      during walking. From this, the sensitivity of the accelerometer was determined.
      During ULLS, the number of steps detected by the accelerometer with an MPAA--the
      minimum MPAA during walking was computed and the specificity of the accelerometer
      was determined. RESULTS: The sensitivity of the accelerometer during walking was
      96% and the specificity during ULLS was 97%. CONCLUSION: An accelerometer is an
      accurate tool to quantify the number of steps taken during walking and it may be
      used to measure subject compliance during ULLS.

PMID- 16964747
TI  - Automatic detection of bubbles in the subclavian vein using Doppler ultrasound
      signals.
AB  - INTRODUCTION: It is possible to detect venous gas bubbles by listening to the
      Doppler audio signals. However, a serious disadvantage of the audio evaluation is
      the inability of continuous monitoring and the inter-rater agreement. Several
      researchers have worked on the automated detection of emboli, but no current
      system has the required sensitivity and specificity for clinical use. METHOD: We
      developed software that integrated frequency filtering, processing, and detection
      phases of microemboli into a graphical user interface. The detection algorithm
      consists of a rule-based criterion with a user-defined threshold sliding in-time
      axis that estimates the duration of the embolic event. Subclavian Doppler audio
      recordings obtained from a high altitude diving expedition were analyzed using
      digital filtering and non-linear operator combinations of the software. The data
      set includes 43 embolic events in 9 recordings from 4 different subjects.
      RESULTS: It was determined that embolic signals are best differentiated from the
      background signal at the 4500-8000-Hz frequency band. By using the non-linear
      "Teager Energy Operator", embolic signals were amplified against their background
      and a high level of sensitivity and specificity was obtained (83.7% and 97.3%,
      respectively). The duration of the detected emboli was estimated as 12.17 +/-
      4.36 ms (mean +/- SD). DISCUSSION: The optimal frequency band for the detection
      of subclavian emboli is significantly higher than previous findings for the
      transcranial site. The duration output of the software can be used to estimate
      the size and the composition of emboli. Successful integration of the software
      into an ambulatory detection system may provide important site-specific bubble
      size distribution data for decompression modeling.

PMID- 16964748
TI  - Fatigue and related human factors in the near crash of a large military aircraft.
AB  - INTRODUCTION: During approach to a remote island location, a U.S. Air Force heavy
      airlift aircraft was flown into an aerodynamic stall, resulting in the loss of
      more than 4000 ft of altitude, with the crew recovering the aircraft just before
      impact would have occurred. METHODS: An analysis of the mishap was conducted
      through a review of non-privileged USAF mishap data, cockpit voice recordings,
      flight data records, and interviews of the aircrew involved. A thorough
      examination of fatigue-related factors was conducted, including computerized
      fatigue modeling. RESULTS: The crew traveled over 11,000 mi in a westward
      direction over a 6-d period. They had been on duty for nearly 21 h on the day of
      the mishap, with minimal in-flight rest. The pilots were late beginning their
      descent for landing, and a minor aircraft malfunction distracted the crew,
      contributing to channelized attention and degraded situational awareness. A
      breakdown in crew communication and failure to adequately monitor and interpret
      true aircraft state culminated in loss of aircraft control. Analysis of the
      crew's work/rest schedule confirmed that multiple elements of fatigue were
      present during this mishap, including acute and cumulative fatigue, circadian
      disruptions, and sleep inertia. Additionally, reduced situational awareness and
      spatial disorientation, exacerbated by the underlying fatigue, were causal in
      this mishap. DISCUSSION: This mishap highlights the importance of maintaining a
      high degree of situational awareness during long-haul flights with a continuing
      need to address issues regarding spatial disorientation, proper application of
      human engineering principles in modern cockpits, and mitigation of aircrew
      fatigue factors.

PMID- 16964749
TI  - Neurological disorders after repetitive breath-hold diving.
AB  - We report a case of transient neurological disorder compatible with cerebral
      decompression illness in a breath-hold diver. A large right-to-left shunt was
      later detected with contrast transcranial Doppler ultrasound. While the mechanism
      of brain damage is unclear, this observation highlights the need for breath-hold
      divers to avoid excessive nitrogen loading and to refrain from forceful Valsalva
      maneuvers that may contribute to the opening of a patent foramen ovale and lead
      to paradoxical cerebral embolism. Because decompression illness is a possibility,
      anyone who experiences unusual symptoms after breath-hold diving should seek
      immediate medical attention.

PMID- 16964750
TI  - Pandemic influenza: a note on international planning to reduce the risk from air
      transport.
AB  - The rapid and intercontinental spread of avian influenza in 2005 and the
      potential for human pandemic influenza caused preparedness plans for such an
      event to be highlighted. The World Health Organization (WHO) has developed a
      global influenza preparedness plan, but this document does not address in detail
      the contribution necessary by the aviation community. The International Civil
      Aviation Organization, with assistance from WHO, the Airports Council
      International, and the International Air Transport Association, and others, has
      developed preparedness guidelines that are in accord with those of WHO but which
      are focused on the aviation aspects. Effective communication between stakeholders
      is the single most important issue that is addressed in the preparedness
      guidelines. States are recommended to appoint a clear contact point at the
      national aviation level that has responsibility for ensuring that all
      stakeholders are adequately consulted in the development of an aviation
      preparedness plan and that the relevant communication links are established. It
      is also important that the aviation preparedness plan is incorporated into the
      State's general preparedness plan, which demands efficient collaboration between
      the departments of health and transport at the government level. Communication
      with passengers, and those considering traveling, is important so that
      individuals are made aware of the risks associated with travel to particular
      parts of the globe and of the risk-reduction measures they may experience, or can
      take themselves, at airports and on aircraft. The guidelines will be web-based
      and will evolve as more knowledge becomes available.

PMID- 16964751
TI  - Prostate cancer.
AB  - Prostate cancer is the most common malignancy in American men and second only to
      lung cancer in deaths. The American Cancer Society estimates that there will be
      about 232,090 new cases of prostate cancer in the United States in 2005, and
      about 30,350 men will die of this disease. Over the past 15 yr, research has
      expanded our knowledge of this cancer, its risk factors, treatments, and the
      potential screening tools. Yet, there is no clear consensus of how to deal with
      every man who comes in for aeromedical certification, how to screen for it, and
      how to treat it. No man is the same when it comes to prostate cancer. It is the
      responsibility of the aviation medical examiner to evaluate the unique aspects of
      every case for aeromedical implications.

PMID- 16964752
TI  - You're the flight surgeon. Anisocoria.

PMID- 16964753
TI  - Ballooning accidents.

PMID- 16964754
TI  - Human performance optimization in aviation.

PMID- 16964755
TI  - Chemical constituents of the root of Dystaenia takeshimana and their anti
      inflammatory activity.
AB  - In our ongoing search for bioactive compounds originating from the endemic
      species in Korea, we found that the hexane and EtOAc fractions of the MeOH
      extract from the root of Dystaenia takeshimana (Nakai) Kitagawa (Umbelliferae)
      showed cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) dual inhibitory
      activity by assessing their effects on the production of prostaglandin D2 (PGD2)
      and leukotriene C4 (LTC4) in mouse bone marrow-derived mast cells. By activity
      guided fractionation, five coumarins, viz. psoralen (2), xanthotoxin (3),
      scopoletin (4), umbelliferone (5), and (+)-marmesin (6), together with beta
      sitosterol (1), were isolated from the hexane fraction, and two phenethyl alcohol
      derivatives, viz. 2-methoxy-2-(4'-hydroxyphenyl)ethanol (7) and 2-hydroxy-2-(4'
      hydroxyphenyl)ethanol (8), three flavonoids, viz. apigenin (9), luteolin (10),
      and cynaroside (11), as well as daucosterol (12) were isolated from the EtOAc
      fraction using silica gel column chromatography. In addition, D-mannitol (13) was
      isolated from the BuOH fraction by recrystallization. Two of the coumarins,
      scopoletin (4) and (+)-marmesin (6), the two phenethyl alcohol derivatives (7, 8)
      and the three flavonoids (9-11) were isolated for the first time from this plant.
      Among the compounds isolated from this plant, the five coumarins as well as the
      three flavonoids showed COX-2/5-LOX dual inhibitory activity. These results
      suggest that the anti-inflammatory activity of D. takeshimana might in part occur
      via the inhibition of the generation of eicosanoids.

PMID- 16964756
TI  - Four butenolides are novel cytotoxic compounds isolated from the marine-derived
      bacterium, Streptoverticillium luteoverticillatum 11014.
AB  - Four known butenolides were isolated from the ethyl acetate extracts of the
      culture broth of the marine-derived bacterium, Streptoverticillium
      luteoverticillatum, by bioassay-guided fractionation. The structures were
      identified on the basis of spectral data. The absolute configuration of compound
      (1) was determined by CD spectrum for the first time. Compounds 1-4 showed in
      vitro cytotoxicity against the murine lymphoma P388 and human leukemia K562 cell
      lines. This is the first report on the isolation of butenolides from the marine
      bacterium, Streptoverticillium luteoverticillatum, and their cytotoxic
      activities.

PMID- 16964757
TI  - Aporphine alkaloids and their reversal activity of multidrug resistance (MDR)
      from the stems and rhizomes of Sinomenium acutum.
AB  - Chromatographic separation of the MeOH extract from the stems and rhizomes of
      Sinomemium acutum led to the isolation of nine alkaloids and a lignan. Their
      structures were determined to be dauriporphine (1), bianfugecine (2),
      dauriporphinoline (3), menisporphine (4), (-)-syringaresinol (5), N
      feruloyltyramine (6), acutumine (7), dauricumine (8), sinomenine (9), and
      magnoflorine (10) by spectroscopic means. These compounds were examined for their
      P-gp mediated MDR reversal activity in human cancer cells. Compound 1 showed the
      most potent P-gp MDR inhibition activity with an ED50 value 0.03 microg/mL and
      0.00010 microg/mL in the MES-SA/DX5 and HCT15 cells, respectively.

PMID- 16964758
TI  - Modulation of activator protein-1 (AP-1) and MAPK pathway by flavonoids in human
      prostate cancer PC3 cells.
AB  - In last couple of decades the use of natural compounds like flavonoids as
      chemopreventive agents has gained much attention. Our current study focuses on
      identifying chemopreventive flavonoids and their mechanism of action on human
      prostate cancer cells. Human prostate cancer cells (PC3), stably transfected with
      activator protein 1 (AP-1) luciferase reporter gene were treated with four main
      classes of flavonoids namely flavonols, flavones, flavonones, and isoflavones.
      The maximum AP-1 luciferase induction of about 3 fold over control was observed
      with 20 microM concentrations of quercetin, chrysin and genistein and 50 microM
      concentration of kaempferol. At higher concentrations, most of the flavonoids
      demonstrated inhibition of AP-1 activity. The MTS assay for cell viability at 24
      h showed that even at a very high concentration (500 microM), cell death was
      minimal for most of the flavonoids. To determine the role of MAPK pathway in the
      induction of AP-1 by flavonoids, Western blot of phospho MAPK proteins was
      performed. Four out of the eight flavonoids namely kaempferol, apigenin,
      genistein and naringenin were used for the Western Blot analysis. Induction of
      phospho-JNK and phospho-ERK activity was observed after two hour incubation of
      PC3-AP1 cells with flavonoids. However no induction of phospho-p38 activity was
      observed. Furthermore, pretreating the cells with specific inhibitors of JNK
      reduced the AP-1 luciferase activity that was induced by genistein while
      pretreatment with MEK inhibitor reduced the AP-1 luciferase activity induced by
      kaempferol. The pharmacological inhibitors did not affect the AP-1 luciferase
      activity induced by apigenin and naringenin. These results suggest the possible
      involvement of JNK pathway in genistein induced AP-1 activity while the ERK
      pathway seems to play an important role in kaempferol induced AP-1 activity.

PMID- 16964759
TI  - Effects of tributyltin chloride on L-DOPA-induced cytotoxicity in PC12 cells.
AB  - Tributyltin chloride (TBTC) at concentrations of 0.5-1.0 microM inhibits dopamine
      biosynthesis in PC12 cells. In this study, the effects of TBTC on L-3,4
      dihydroxyphenylalanine (L-DOPA)-induced cytotoxicity in PC12 cells were
      investigated. TBTC at concentrations up to 1.0 microM neither affected cell
      viability, nor induced apoptosis after 24 or 48 h in PC12 cells. However, TBTC at
      concentrations higher than 2.0 microM caused cytotoxicity through an apoptotic
      process. In addition, exposure of PC12 cells to non-cytotoxic (0.5 and 1.0
      microM) or cytotoxic (2.0 microM) concentrations of TBTC in combination with L
      DOPA (20, 50 and 100 microM) resulted in a significant increase in cell loss and
      the percentage of apoptotic cells after 24 or 48 h compared with TBTC or L-DOPA
      alone. The enhancing effects of TBTC on L-DOPA-induced cytotoxicity were
      concentration- and treatment time-dependent. These data demonstrate that TBTC
      enhances L-DOPA-induced cytotoxicity in PC 12 cells.

PMID- 16964760
TI  - Chemopreventive effect of saponins derived from roots of Platycodon grandiflorum
      on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in
      A/J mice.
AB  - This study examined the chemopreventive effect of saponins that were isolated
      from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil
      saponins (CKS), against the tobacco-specific carcinogen, 4-(methylnitrosamino)-1
      (3-pyridyl)-1-butanone (NNK), -on lung tumorigenesis in A/J mice. The mice were
      treated with a single NNK dose (100 mg/kg b.w., i.p.). CKS (0.5, 1,4 mg/kg body
      wt.) was administered orally daily for 3 days/week beginning 1 day after the NNK
      treatment and was maintained throughout the experiment. The administration of CKS
      suppressed the NNK-induced increase in the level of proliferating cell nuclear
      antigen, which are a marker of cell proliferation, in the lungs of the mice 4
      weeks after the NNK injection. Twenty-five weeks after the NNK treatment, the
      mice were sacrificed and the number of surface lung tumors was measured. CKS
      significantly reduced the number of lung tumors induced by NNK in a dose
      dependent manner. These results suggest that CKS suppresses the development of
      lung tumors and has a chemopreventive effect against NNK-induced mouse lung
      tumorigenesis.

PMID- 16964761
TI  - Structure-activity relationships of dimethylsphingosine (DMS) derivatives and
      their effects on intracellular pH and Ca2+ in the U937 monocyte cell line.
AB  - We recently reported that dimethylsphingosine (DMS), a metabolite of
      sphingolipids, increased intracellular pH and Ca2+ concentration in U937 human
      monocytes. In the present study, we found that dimethylphytosphingosine (DMPH)
      induced the above responses more robustly than DMS. However, phytosphingosine,
      monomethylphytosphingosine or trimethylsphingosine showed little or no activity.
      Synthetic C3 deoxy analogues of sphingosine did show similar activities, with the
      C16 analogue more so than C18. The following structure-activity relationships
      were observed between DMS derivatives and the intracellular pH and Ca2+
      concentrations in U937 monocytes; 1) dimethyl modification is important for the
      DMS-induced increase of intracellular pH and Ca2+, 2) the addition of an OH group
      on C4 enhances both activities, 3) the deletion of the OH group on C3 has a
      negligible effect on the activities, and 4) C16 appears to be more effective than
      C18. We also found that W-7, a calmodulin inhibitor, blocked the DMS-induced pH
      increase, whereas, KN-62, ML9, and MMPX, specific inhibitors for calmodulin
      dependent kinase II, myosin light chain kinase, and Ca(2+)-calmodulin-dependent
      phosphodiesterase, respectively, did not affect DMS-induced increases of pH in
      the U937 monocytes.

PMID- 16964762
TI  - Differential expression of gangliosides in the ovary and uterus of streptozotocin
      induced and db/db diabetic mice.
AB  - Gangliosides are widely distributed in mammalian cells and play important roles
      in various functions such as cell differentiation and growth control. In
      addition, diabetes and obesity cause abnormal development of reproductive
      processes in a variety of species. However, the mechanisms underlying these
      effects, and how they are related, are not fully understood. This study examined
      whether the differential expression of gangliosides is implicated in the abnormal
      follicular development and uterine architecture of streptozotocin (STZ)-induced
      and db/db diabetic mice. Based upon the mobility on high-performance thin-layer
      chromatography, mouse ovary consisted of at least five different ganglioside
      components, mainly gangliosides GM3, GM1, GD1a and GT1b, and diabetic ovary
      exhibited a significant reduction in ganglioside expression with apparent changes
      in the major gangliosides. A prominent immunofluorescence microscopy showed a
      dramatic loss of ganglioside GD1a expression in the primary, secondary and
      Graafian follicles of STZ-induced and db/db diabetic mice. A significant decrease
      in ganglioside GD3 expression was also observed in the ovary of db/db mice. In
      the uterus of STZ-induced diabetic mice, expression of gangliosides GD1a and GT1b
      was obviously reduced, but gangliosides GM1, GM2 and GD3 expression was
      increased. In contrast, the uterus of db/db mice showed a significant increase in
      gangliosides GM1, GD1a and GD3 expression. Taken together, a complex pattern of
      ganglioside expression was seen in the ovary and uterus of normoglycemic ICR and
      db/+ mice, and the correspoding tissues in diabetic mice are characterized by
      appreciable changes of the major ganglioside expression. These results suggest
      that alterations in ganglioside expression caused by diabetes mellitus may be
      implicated in abnormal ovarian development and uterine structure.

PMID- 16964763
TI  - Attenuation of morphine tolerance and withdrawal syndrome by coadministration of
      nalbuphine.
AB  - Morphine has been used widely on the treatment of many types of chronic pain.
      However the development of tolerance to and dependence on morphine by repeat
      application is a major problem in pain therapy. The purpose of the present study
      was to investigate whether combined administration of nalbuphine with morphine
      affects the development of tolerance to and dependence on morphine. We
      hypothesize that the use of nalbuphine, kappa-agonist may prove to be useful
      adjunct therapy to prevent morphine-induced undesirable effects in the management
      of some forms of chronic pain. Morphine (10 mg/kg) was injected to rats
      intraperitoneally for 5 day. The variable dose of nalbuphine (0.1, 1.0 and 5.0
      mg/kg) was administered (i.p.) in combination with morphine injection. The
      development of morphine tolerance was assessed by measuring the antinociceptive
      effect with the Randall-Selitto apparatus. The development of dependence on
      morphine was determined by the scoring the precipitated withdrawal signs for 30
      min after injection of naloxone (10 mg/kg, i.p.). Nalbuphine did not attenuate
      antinociceptive effect of morphine in rats. Interestingly, combined
      administration of morphine with nalbuphine (10:1) significantly attenuated the
      development of dependence on morphine. The elevation of [3H]MK-801 binding in
      frontal cortex, dentate gyrus, and cerebellum after chronic morphine infusion was
      suppressed by the coadministration of nalbuphine. In addition, the elevation of
      NR1 expression by morphine was decreased by the coadministration of nalbuphine in
      rat cortex. These results suggest that the coadministration of nalbuphine with
      morphine in chronic pain treatment can be one of therapies to reduce the
      development of tolerance to and dependence on morphine.

PMID- 16964764
TI  - Inhibitory effect of ginsenoside Rg5 and its metabolite ginsenoside Rh3 in an
      oxazolone-induced mouse chronic dermatitis model.
AB  - The effect of a main constituent ginsenoside Rg5 isolated from red ginseng and
      its metabolite ginsenoside Rh3 in a chronic dermatitis model was investigated.
      Ginsenosides Rg5 and Rh3 suppressed swelling of oxazolone-induced mouse ear
      contact dermatitis. These ginsenosides also reduced mRNA expressions of
      cyclooxygenase-2, interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha and
      interferon (IFN)-gamma. The inhibition of ginsenoside Rh3 was more potent than
      that of ginsenoside Rg5. These findings suggest that ginsenoside Rh3 metabolized
      from ginsenoside Rg5 may improve chronic dermatitis or psoriasis by the
      regulation of IL-1beta and TNF-alpha produced by macrophage cells and of IFN
      gamma produced by Th cells.

PMID- 16964765
TI  - Dexamethasone inhibits the formation of multinucleated osteoclasts via down
      regulation of beta3 integrin expression.
AB  - Although glucocorticoids are known to affect osteoclast differentiation and
      function, there have been conflicting reports about the effect of glucocorticoids
      on osteoclast formation, leading to the assumption that microenvironment and cell
      type influence their action. We explored the effect of the synthetic
      glucocorticoid analog dexamethasone on the formation of osteoclasts.
      Dexamethasone inhibited the formation of tartrate-resistant acid phosphatase
      (TRAP)-positive multinucleated osteoclasts without affecting the formation of
      TRAP-positive mononuclear cells in a coculture of mouse osteoblasts and bone
      marrow cells. Dexamethasone did not inhibit mRNA expression levels of the
      receptor activator of nuclear factor-kappaB ligand and osteoprotegerin, the
      essential regulators of osteoclastogenesis. Dexamethasone down-regulated the
      expression of beta3 integrin mRNA and protein but did not alter expression of
      other osteoclast differentiation marker genes. Both dexamethasone and echistatin,
      a beta3 integrin function blocker, inhibited TRAP-positive multinucleated
      osteoclast formation but not TRAP-positive mononuclear cell formation. These
      results suggest that dexamethasone inhibits the formation of multinucleated
      osteoclasts, at least in part, through the down-regulation of beta3 integrin,
      which plays an important role in the formation of multinucleated osteoclasts.

PMID- 16964766
TI  - Antioxidant and neuroprotective effects of hesperidin and its aglycone
      hesperetin.
AB  - The present study evaluated antioxidant and neuroprotective activities of
      hesperidin, a flavanone mainly isolated from citrus fruits, and its aglycone
      hesperetin using cell-free bioassay system and primary cultured rat cortical
      cells. Both hesperidin and hesperetin exhibited similar patterns of 1,1-diphenyl
      2-picrylhydrazyl radical scavenging activities. While hesperidin was inactive,
      hesperetin was found to be a potent antioxidant, inhibiting lipid peroxidation
      initiated in rat brain homogenates by Fe2+ and L-ascorbic acid. In consistence
      with these findings, hesperetin protected primary cultured cortical cells against
      the oxidative neuronal damage induced by H2O2 or xanthine and xanthine oxidase.
      In addition, it was shown to attenuate the excitotoxic neuronal damage induced by
      excess glutamate in the cortical cultures. When the excitotoxicity was induced by
      the glutamate receptor subtype-selective ligands, only the N-methyl-D-aspartic
      acid-induced toxicity was selectively and markedly inhibited by hesperetin.
      Furthermore, hesperetin protected cultured cells against the A(beta(25-35))
      induced neuronal damage. Hesperidin, however, exerted minimal or no protective
      effects on the neuronal damage tested in this study. Taken together, these
      results demonstrate potent antioxidant and neuroprotective effects of hesperetin,
      implying its potential role in protecting neurons against various types of
      insults associated with many neurodegenerative diseases.

PMID- 16964767
TI  - Effect of additives on the viability of bifidobacteria loaded in alginate poly-l
      lysine microparticles during the freeze-drying process.
AB  - Bifidobacteria-loaded alginate poly-l-lysine microparticles (bap microparticles)
      were prepared using an air atomization method and then freeze-dried. The
      viability of the bap microparticles was investigated as a function of the amount
      of the bifidobacteria cultures, and the addition of a yeast extract,
      cryoprotectants, antioxidants and neutralizer. The size of the bap microparticles
      with and without the bifidobacteria was 84.8 +/- 28.5 microm (mean +/- standard
      deviation) and 113.1 +/- 38.5 microm, respectively. The surface morphology was
      slightly ellipsoid and wrinkled regardless of the incorporating bifidobacteria.
      The viability gradually decreased with increasing freeze-drying time. Free
      flowing powdered bap microparticles were obtained at least 12 h after freeze
      drying the wetted slurry of bap microparticles. However, the particles tended to
      aggregate when either lactose or ascorbic acid was added. The addition of a yeast
      extract, cryoprotectants (glycerol and lactose), antioxidants (NaHSO3 and
      ascorbic acid) and neutralizer (Mg3(PO4)2) resulted in a significantly higher
      viability of the bifidobacteria in the bap microparticles after freeze-drying
      (0.34-1.84 log) compared with the culture alone.

PMID- 16964768
TI  - Doxorubicin release from core-shell type nanoparticles of poly(DL-lactide-co
      glycolide)-grafted dextran.
AB  - In this study, we prepared core-shell type nanoparticles of a poly(DL-lactide-co
      glycolide) (PLGA) grafted-dextran (DexLG) copolymer with varying graft ratio of
      PLGA. The synthesis of the DexLG copolymer was confirmed by 1H nuclear magnetic
      resonance (NMR) spectroscopy. The DexLG copolymer was able to form nanoparticles
      in water by self-aggregating process, and their particle size was around 50 nm
      approximately 300 nm according to the graft ratio of PLGA. Morphological
      observations using a transmission electron microscope (TEM) showed that the
      nanoparticles of the DexLG copolymer have uniformly spherical shapes. From
      fluorescence probe study using pyrene as a hydrophobic probe, critical
      association concentration (CAC) values determined from the fluorescence
      excitation spectra were increased as increase of DS of PLGA. 1H-NMR spectroscopy
      using D2O and DMSO approved that DexLG nanoparticles have core-shell structure,
      i.e. hydrophobic block PLGA consisted inner-core as a drug-incorporating domain
      and dextran consisted as a hydrated outershell. Drug release rate from DexLG nano
      particles became faster in the presence of dextranase in spite of the release
      rate not being significantly changed at high graft ratio of PLGA. Core-shell type
      nanoparticles of DexLG copolymer can be used as a colonic drug carrier. In
      conclusion, size, morphology, and molecular structure of DexLG nanoparticles are
      available to consider as an oral drug targeting nanoparticles.

PMID- 16964770
TI  - Patient choice: practice dilemma.

PMID- 16964771
TI  - The beauty of silence.
AB  - The distractions around us are not the only things that prevent deep listening.
      Putting ourselves aside can be a vital means of connecting with another.

PMID- 16964772
TI  - Painful delays.
AB  - Delays in reporting symptoms and in referral to a gynaecologist may result in
      women enduring the symptoms of endometriosis for a considerable time.

PMID- 16964773
TI  - Night watch.

PMID- 16964774
TI  - Personal tutor encounters: understanding the experience.
AB  - AIM: To investigate the lived experience of the 'support' relationship between
      students and their personal tutors. METHOD: The purposive sample comprised 36
      personal tutors and 44 pre-registration undergraduate nursing students on diploma
      and degree-level courses (adult, mental health and child branch) from a London
      university school of nursing and a northern university school of nursing. Private
      audiotaped interviews were conducted with the participants. Data analysis was
      undertaken to identify important themes. FINDINGS: The tutees varied in their
      readiness to learn, define, discuss and negotiate support. Positive encounters
      were when the tutees felt supported. Tutors had an overwhelming feeling of
      frustration when tutees lacked study skills and came unprepared to tutorials.
      However, some tutors indicated a high level of empathic understanding for tutees
      and spent much of their personal time supporting them. CONCLUSION: The study
      illuminated the complexity and skill required to be a tutee and a tutor. Tutors'
      individual support style reflected tutees' expectations and perceptions to
      varying degrees. A positive experience by tutees and tutors was perceived when
      each had a shared understanding of the support concept. Mutual trust, engagement,
      respect and accepting responsibilities were important elements of the personal
      tutor and tutee relationship.

PMID- 16964775
TI  - Improving information management in ward nurses' practice.
AB  - The introduction of a national programme for information technology will affect
      nurses' methods of managing clinical information on hospital wards. Within a
      healthcare team, information is managed through formal recording mechanisms as
      well as informal information exchange. Opportunities to combine these two
      approaches are highlighted through scenarios. Recommendations are made for nurses
      to adapt their current information systems and better manage their clinical
      information.

PMID- 16964776
TI  - Exploring person-centred care.
AB  - This article explores the philosophy of person-centred care. Person-centred care
      developed in response to the need for a more patient-sensitive healthcare service
      and is based on a rich understanding of the patient, his or her circumstances and
      needs.

PMID- 16964778
TI  - Anxious moments.

PMID- 16964777
TI  - Venous thromboembolism.

PMID- 16964779
TI  - Nursing in a war zone.

PMID- 16964781
TI  - Migrant tuberculosis: a moving target.

PMID- 16964780
TI  - Prevalence of functional limitations among adults 60 years of age and over:
      United States, 1999-2002.
AB  - In the 1999-2002 National Health and Nutrition Examination Survey (NHANES),
      participants were asked a series of questions designed to evaluate functional
      status. Some questions assessed performance on selected activities of daily
      living (ADLs) and instrumental activities of daily living (IADLs), while others
      assessed mobility, strength, endurance, and social participation. This report
      contains prevalence estimates and standard errors for adults, 60 years of age and
      over, who reported difficulty performing these activities without the aid of
      special equipment or who were not able to perform these activities. Results are
      reported by sex, age group, race and ethnicity, and body mass index (BMI).
      Assessment of functional status plays an important role in monitoring the health
      problems and needs of older Americans.

PMID- 16964782
TI  - Tuberculosis immune reconstitution inflammatory syndrome in countries with
      limited resources.
AB  - Mycobacterium tuberculosis infection accounts for probably one third of human
      immunodeficiency virus (HIV) related immune reconstitution inflammatory syndrome
      (IRIS) events, particularly in developing countries where HIV and tuberculosis
      (TB) co-infection is very common. Small cohort studies of HIV-positive patients
      with active TB treated with antiretroviral therapy (ART) suggest an incidence of
      TB IRIS varying between 11% and 45%. Risk factors for TB IRIS that have been
      suggested in certain studies but not in others include: starting ART within 6
      weeks of starting TB treatment; extra-pulmonary or disseminated disease; a low
      CD4+ lymphocyte count and a high viral load at the start of ART; and a good
      immunological and virological response during highly active antiretroviral
      therapy (HAART). It is important to agree on a clinical case definition of TB
      IRIS that could be used in resource-limited settings. Such a case definition
      could be used to determine the exact incidence and consequences of TB IRIS and
      would be valuable worldwide in clinical trials that are needed to answer
      questions on how this phenomenon could be prevented and treated.

PMID- 16964783
TI  - In the European Union, TB patients from former Soviet countries have a high risk
      of multidrug resistance.
AB  - SETTING: Fourteen countries of the European Union (EU). OBJECTIVE: To explore
      determinants of resistance to isoniazid and rifampicin (multidrug-resistant
      tuberculosis [MDR-TB]) among tuberculosis (TB) patients in the EU. DESIGN: Pooled
      TB case notification data for 2003 from the-Baltic States (Estonia, Latvia,
      Lithuania) and Austria, Belgium, the Czech Republic, Denmark, Finland, Germany,
      Luxembourg, The Netherlands, Slovenia, Sweden and the UK were investigated using
      bivariate and multivariable analysis. RESULTS: Of 12,109 cases with data, MDR-TB
      occurred in 709 cases, 91% of whom were from countries of the former Soviet Union
      (FSU), including the Baltic States. At multivariable analysis, MDR-TB was
      strongly associated with previous treatment in both Baltic and non-Baltic
      countries (adjusted OR 9.5 and 6.4, respectively), and inversely related to age
      >64 years (OR 0.4 and 0.2). In non-Baltic countries, MDR-TB was more strongly
      related to origin from the FSU (OR 19.7, reference non-Baltic EU) than from other
      regions (up to OR 2.3). Among cases pooled from all countries, provenance from
      the FSU was very strongly linked to MDR-TB in both previously untreated (OR 24.9)
      and previously treated (OR 53.7) cases. CONCLUSION: Within a context of
      increasing mobility, public health workers should be aware of a higher risk for
      MDR-TB among patients from the FSU as well as among patients previously treated
      for TB.

PMID- 16964784
TI  - The impact of migrants on the epidemiology of tuberculosis in Beijing, China.
AB  - SETTING: Tuberculosis (TB) services in the Municipality of Beijing, China.
      OBJECTIVE: To evaluate the impact of migrants on the epidemiology and management
      of TB in Beijing. DESIGN: Comparison of information on permanent residents and
      migrants from routine reports of TB cases registered in Beijing from 1993 to
      2005. RESULTS: From 1993 to 2005, there was a steady rise in the proportion of
      migrants among TB cases notified in Beijing, from approximately one in 10 cases
      to one in three cases. The results of treatment in migrant cases of TB over the
      period 1997-2004 were unsatisfactory. The proportion of cases cured among
      permanent residents was 90.6%, compared with only 37.0% of cases among migrants.
      CONCLUSION: Migrants pose a challenge to TB services in Beijing. Special
      attention must be given to them by the National Tuberculosis Programme to address
      these challenges.

PMID- 16964785
TI  - Tuberculosis epidemiology in six provinces of Vietnam after the introduction of
      the DOTS strategy.
AB  - SETTING: Six provinces in Vietnam where the DOTS strategy was introduced in 1989.
      OBJECTIVE: To assess the impact of improved tuberculosis (TB) control on TB
      epidemiology in Vietnam. METHODS: Data from the surveillance system in the period
      1990-2003 were analysed to assess trends of notification rates and the mean ages
      of notified cases. Data from repeated tuberculin surveys in the period 1986-2002
      were estimated to assess the prevalence of TB infection, the annual risk of
      infection and its trend using various cut-off points in those with and without
      bacille Calmette-Guerin (BCG) scar. RESULTS: Age-standardised notification rates
      in the period 1996-2003 declined significantly, by 2.6% to 5.9% per year, in five
      provinces. However, in four provinces notification rates in the age group 15-24
      years increased significantly, by 4.5% to 13.6% per year, during this period. The
      mean age of newly diagnosed patients with smear-positive TB increased up to 1995
      but decreased thereafter. The annual risk of TB infection showed a significant
      annual decrease (4.9% per year) in one province in surveys performed between 1986
      and 1997, and in two provinces (6.6% and 4.7%) in surveys conducted between 1993
      and 2002. CONCLUSION: These data suggest limited impact to date of the DOTS
      strategy in Vietnam.

PMID- 16964786
TI  - Pulmonary tuberculosis in young Korean soldiers: incidence, drug resistance and
      treatment outcomes.
AB  - OBJECTIVE: To determine the incidence and treatment outcomes of pulmonary
      tuberculosis (PTB) in young soldiers of South Korea. DESIGN: From 2000 to 2004,
      all soldiers with a new diagnosis of tuberculosis (TB) were enrolled in the
      study, based on the official records of the Armed Forces Medical Command. The
      demographic and clinical data of the cases were evaluated retrospectively.
      RESULTS: A total of 3115 TB cases were reported during the study period, of whom
      2071 (66.5%) were reported as PTB. The annual incidence rates of PTB were 96.4
      per 100,000 population in 2000, 89.3 in 2001, 67.6 in 2002, 60.2 in 2003, and
      63.1 in 2004. A total of 270 patients diagnosed and treated at the Armed Forces
      Capital Hospital were analysed. Of the Mycobacterium tuberculosis isolates, 87.4%
      were susceptible to all available anti-tuberculosis drugs; 253 (93.7%) patients
      eventually completed initial anti-tuberculosis treatment. Among the patients with
      smear-positive PTB, the cure rate was 89.3% (100/112). CONCLUSION: Our results
      demonstrate that the incidence of PTB in Korean soldiers, although still high,
      was declining steadily. With good case management, the overall success rate of
      initial treatment was approximately 90%.

PMID- 16964787
TI  - Tuberculosis control in conflict-affected East Timor, 1996-2004.
AB  - SETTING: East Timor has undergone major political changes in the past 10 years.
      Tuberculosis (TB) control has flourished, despite chronic low tension conflict, a
      brief but intense period of high-level conflict and post-conflict reconstruction.
      OBJECTIVE: To assess TB control in East Timor from 1996 to 2004. DESIGN: Data
      were collected from a variety of sources. Key TB programme indicators were
      analysed with reference to WHO targets to assess the performance of the three TB
      control programmes that operated during the study period. RESULTS: Before 1999, a
      non-governmental TB control programme was established in several districts in
      parallel with the government TB programme, and showed optimistic results.
      External donor funds, technical assistance and local control strategies were key
      components. In 1999, conflict led to complete disruption of both programmes. In
      2000, a National Tuberculosis Control Programme (NTP) was established from the
      non-governmental programme in collaboration with other partners. The smear
      positive TB case notification rate of 108 per 100000 population is the highest in
      the region and reflects high population coverage. The cure rate of 81% is close
      to reaching the WHO target. CONCLUSION: High-quality TB control has been
      introduced in conflict-affected East Timor. Further research is needed to examine
      Timorese approaches to inform other, similar settings.

PMID- 16964788
TI  - Private GPs contribute to TB control in Myanmar: evaluation of a PPM initiative
      in Mandalay Division.
AB  - SETTING: Mandalay Division, Myanmar. AIM: To assess the effect of an initiative
      to involve private general practitioners (GPs) in the National Tuberculosis
      Programme (NTP) and to identify lessons learnt for public-private mix scale-up.
      METHODS: Source of referral/diagnosis and place of treatment were included in the
      routine recording and reporting systems to enable disaggregated analysis of the
      contribution of GPs to case notification and treatment outcomes. Case
      notification trends were compared between the intervention and control areas over
      a 4-year period. RESULTS: Private GPs contributed 44% of new smear-positive cases
      registered during the study period (July 2002-December 2004). The notification of
      new sputum smear-positive TB in the study area increased by 85% between the year
      prior to the GP involvement and 2 years after (from 46 to 85/100,000). Case
      notification increased by 57% in the control townships and by 42% in all of
      Mandalay Division. The treatment success rate for new smear-positive cases
      treated by GPs was 90%. CONCLUSIONS: The involvement of private GPs substantially
      increased TB case notification, while a high treatment success rate was
      maintained. Success factors include a well-developed local medical association
      branch, strong managerial support, training and supervision by the public sector
      and provision of drugs and consumables free of charge by the NTP.

PMID- 16964789
TI  - Joining the DOTS in Bali: private practitioners' perceptions of tuberculosis
      control.
AB  - SETTING: The Indonesian island of Bali has both a national public tuberculosis
      (TB) programme and a significant private sector that provides treatment for
      patients with TB. OBJECTIVE: To explore private practitioners' perceptions of
      barriers to the treatment of patients with TB in Bali to inform strategies for
      future programme development. DESIGN: Semi-structured interviews were conducted
      with private practitioners who treated TB patients in their private practice.
      RESULTS: The main barriers to improved TB control in Bali identified by private
      practitioners reflect difficulties encountered within the following four areas:
      patient nonadherence to treatment, limitations of public services, public-private
      integration and limitations of private services. Private practitioners identified
      the need for improvements in the level of community education regarding TB, the
      degree of public-private interaction, the quality of diagnostic services and
      practitioner access to training. CONCLUSION: This study identified both strengths
      and weaknesses for TB control in the private sector, as well as considerable
      variations in perceptions and practice among private practitioners. The
      development of strategies to address these difficulties and utilise the inherent
      strengths of both public and private practitioners will be essential for improved
      service provision and TB control in Bali.

PMID- 16964790
TI  - Health care seeking among individuals with cough and tuberculosis: a population
      based study from rural India.
AB  - SETTING: Ujjain district, Madhya Pradesh, India. OBJECTIVE: To describe and
      compare health care seeking among men and women with cough of >3 weeks, with
      special focus on the utilisation of private and public health care. DESIGN: A
      population-based cross-sectional survey including 45 719 individuals aged > or =
      15 years. RESULTS: The prevalence of cough was respectively 2.8% and 1.2% among
      men and women. The majority of men and women reported seeking health care for
      their symptoms (69% vs. 71%), but only 23% visited a public provider at some
      point during their illness. A similar health care seeking pattern was found for
      patients diagnosed with tuberculosis (TB) in our survey. No significant
      differences in health care seeking were found between men and women. Only 13% of
      those seeking care reported having had a sputum smear examination since the onset
      of cough. Factors associated with sputum examination were history of TB,
      haemoptysis and visiting a public provider. CONCLUSION: The low utilisation of
      public health care services and the few sputum examinations reported in this
      rural Indian setting illustrate the need for improved diagnostic practices as
      well as involvement of private providers in TB control activities.

PMID- 16964791
TI  - Pulmonary TB and NTM lung disease: comparison of characteristics in patients with
      AFB smear-positive sputum.
AB  - OBJECTIVE: To compare the clinical and radiographic features of pulmonary
      tuberculosis (PTB) and non-tuberculous mycobacteria (NTM) lung disease in
      patients with acid-fast bacilli (AFB) positive sputum specimens. DESIGN: The
      initial clinical and radiographic features of 229 PTB patients were compared with
      those of 70 patients with NTM lung disease. The most commonly involved organisms
      in the NTM lung disease cases were Mycobacterium avium complex (n = 38, 54%) and
      M. abscessus (n = 26, 37%). RESULTS: Clinical and radiographic findings that were
      more common in patients with NTM lung disease than in PTB patients were: older
      age (P < 0.001), non-smoker (P < 0.001), history of previous TB treatment (P <
      0.001), absence of pleural effusion (P = 0.017), involvement of middle and/or
      lower lung zones (P = 0.007), and bilateral disease (P = 0.005). Multivariate
      analysis showed that older age (> or = 40 years), non-smoker, previous TB
      treatment, absence of pleural effusion and involvement of middle and/or lower
      lung zones were significant independent predictors for NTM lung disease.
      CONCLUSIONS: There is considerable overlap in the clinical and radiographic
      appearances of PTB and NTM lung disease. The isolation and identification of
      causative organisms are mandatory for a correct diagnosis in patients with AFB
      positive sputum specimens.

PMID- 16964792
TI  - Social impact of tuberculosis in southern Thailand: views from patients, care
      providers and the community.
AB  - BACKGROUND: There is growing recognition that attention to social and behavioral
      factors in tuberculosis (TB) control needs to complement biomedical emphasis on
      better drugs, vaccines and new diagnostic tools. METHODS: Using qualitative
      methods, we conducted 10 focus groups and seven individual interviews to explore
      how TB is perceived or experienced in southern Thailand. Participants included
      male and female patients with TB, patients with AIDS, TB care providers, family
      members of patients with TB, religious leaders (Buddhist and Muslim), and
      unaffected community members. RESULTS: Responses informed two conceptual
      frameworks on stigma and social support. The first model dichotomized the meaning
      of TB into 'good' and 'bad' factors related to social support and stigma,
      respectively. The second model identified three themes--disease severity,
      religion, and knowledge of TB--linked to either stigma, social support, or both.
      CONCLUSION: Social support as a facilitator and stigma as a barrier are
      diametrically opposed concepts that need to inform TB care and treatment.
      Interventions to reduce stigma and promote social support at the patient,
      household, community, and health care system levels should be part of future
      efforts in the control of TB in Thailand.

PMID- 16964793
TI  - Perceptions and experiences of tuberculosis among African patients attending a
      tuberculosis clinic in London.
AB  - SETTING: Little is known of the social and cultural issues influencing the uptake
      of and attitudes to tuberculosis (TB) care by people of African extraction living
      in the UK. OBJECTIVE: To describe the perceptions and experiences of African
      patients with TB in London, focusing on issues relating to diagnosis, treatment
      adherence and stigma. DESIGN: Qualitative study using in-depth interviews.
      RESULTS: Misinterpretation of early symptoms led to delays in seeking health
      care. Although half of the respondents reported denial of the diagnosis, they
      reported good treatment adherence, noting the role of TB specialist nurses in
      promoting adherence. Respondents felt stigmatised by the diagnosis, although
      actual experiences of stigma were rare. Experience of TB in a known person
      mitigated stigma. Human immunodeficiency virus (HIV) disease was perceived to
      have worsened TB stigma, and most patients offered HIV testing initially
      declined, fearing stigmatisation and poor illness outcomes if positive.
      CONCLUSIONS: Awareness of TB can be improved among migrants at high risk of
      developing the disease and among health professionals. Counselling around HIV
      testing for TB patients must take their beliefs into account if a high uptake of
      testing is to be achieved.

PMID- 16964794
TI  - Tuberculosis at Chris Hani Baragwanath Hospital: an intervention to improve
      patient referrals to district clinics.
AB  - SETTING: A study in 2001 described the process of managing tuberculosis (TB) at
      Chris Hani Baragwanath hospital, the numbers of patients diagnosed and poor
      outcomes of referring patients to clinics in the adjacent sub-districts. The
      present study describes and evaluates an intervention to address the problems.
      OBJECTIVES: To describe the intervention process (education and referral of TB
      patients) and the subsequent results over a 2-year period from 2003 to 2005.
      METHODS: The process of establishing the system and how it was evaluated at
      district clinics in Johannesburg are described. RESULTS: In the first 2 years of
      operation, August 2003 to July 2005, 13,138 patients were registered. Extra
      pulmonary tuberculosis (EPTB) was diagnosed in 34%. Of the 46% tested for human
      immunodeficiency virus (HIV), 93% were positive. Successful referral to clinics
      was achieved for 94% of patients. CONCLUSIONS: Very large numbers of patients are
      diagnosed with TB at Chris Hani Baragwanath Hospital. A TB care centre has
      successfully addressed important referral, education and registration
      requirements for the comprehensive management of TB with links to clinics. It is
      suggested that this model be applied at other hospitals.

PMID- 16964795
TI  - Mixture analysis of tuberculin survey data from northern Malawi and critique of
      the method.
AB  - SETTING: Various methods have been used to estimate the prevalence of
      Mycobacterium tuberculosis infection from tuberculin survey data. All are
      complicated by prior sensitisation to environmental mycobacteria and bacille
      Calmette-Guerin (BCG) vaccination. Mixture analysis has recently been proposed as
      a means of overcoming misclassification and improving infection prevalence
      estimates. OBJECTIVE: To compare conventional and mixture model estimates of M.
      tuberculosis infection prevalence. DESIGN: Mixture models with two or three
      univariate normal components were fitted to the results of 53 909 tuberculin
      tests conducted in northern Malawi during 1980-1984. Data were stratified by BCG
      status, sex and age and corrected for digit preference. Prevalence estimates
      derived from mixture models were compared with those of conventional methods.
      RESULTS: The optimal model was age-dependent, with three- and one-component
      solutions preferred in younger and older age groups, respectively. In contrast
      with findings from elsewhere, a component corresponding to BCG vaccination was
      indistinguishable from that attributable to environmental mycobacterial exposure,
      and infection prevalence estimates in younger individuals with a BCG scar were
      inflated, irrespective of the method used. CONCLUSION: The validity of infection
      prevalence and incidence estimates based on mixture modelling is probably locale
      dependent, and the assumptions underlying mixture models may not realistically
      reflect underlying immunological processes.

PMID- 16964796
TI  - Efficiency of serial smear examinations in excluding sputum smear-positive
      tuberculosis.
AB  - SETTING: This study determined the number of slides required to identify one
      additional case of sputum smear-positive tuberculosis (TB) from the third smear.
      The study hypothesis was that not more than 100 and 75 slides, respectively, in
      Mongolia and Zimbabwe, need to be examined to find one additional case of TB with
      a third serial diagnostic sputum smear examination. METHODS: In a retrospective,
      record-based study, data were abstracted from TB laboratory registers from all 31
      laboratories in Mongolia and 23 randomly selected laboratories in Zimbabwe using
      a uniform EpiData collection instrument. RESULTS: A total of 52,909 records of
      examinees were available. In Mongolia, of 15 103 suspects, 1717 (11.4%) were
      positive. Of these, 0.7% were positive for the first time on the third smear
      examination. In Zimbabwe, of 25 693 suspects, 3452 (13.4%) were positive and 4.5%
      were positive only on the third smear examination. The expected number of slides
      required to detect one additional case on the third examination was 1153.3 for
      Mongolia and 132.6 for Zimbabwe. CONCLUSIONS: The requirement of routine
      examination of three serial smears before declaring a suspect as a 'non-case' (of
      sputum smear-positive TB) will need to be reviewed in both Mongolia and Zimbabwe.

PMID- 16964797
TI  - Associated tuberculosis and diabetes in Conakry, Guinea: prevalence and clinical
      characteristics.
AB  - SETTING: Anti-tuberculosis centres in Conakry. OBJECTIVES: To determine the
      prevalence of diabetes mellitus in patients with tuberculosis (TB), identify the
      associated risk factors and describe the clinical signs of the association of TB
      and diabetes. METHOD: A total of 388 patients with TB selected by simple random
      sampling from the register of cases diagnosed in Conakry were examined and
      administered a capillary blood glycaemia test to detect diabetes. RESULTS:
      Thirteen cases of diabetes were identified, giving a prevalence rate of 3.35%
      (95%CI 1.35-5.35). Four (31%) had not been diagnosed before the survey. The
      diagnosis of diabetes preceded that of TB by an average of 5 years (range 1-9
      years). The clinical characteristics of TB (frequent exposure to infection, site
      and proportion of new and retreated cases) did not differ from one group to
      another. Increased age (P < 0.0001), obesity (P < 0.005), sedentary lifestyle (P
      < 0.0004), and previous family history of diabetes (P = 0.04) or obesity (P =
      0.04) were significantly associated with diabetes. CONCLUSION: The prevalence of
      diabetes among TB patients is higher than previously estimated for Guinea.
      Because of frequent co-morbidity, systematic testing for diabetes among TB
      patients may be recommended, particularly if risk factors are present.

PMID- 16964798
TI  - Tuberculosis of the bone marrow: clinico-pathological study of 22 cases from
      Saudi Arabia.
AB  - OBJECTIVE: To study the clinical and pathological patterns of tuberculosis (TB)
      involving the bone marrow in a tertiary care setting. METHODS: A retrospective
      study of cases of bone marrow TB diagnosed and treated at King Faisal Specialist
      Hospital and Research Center from 1990 to 2002. The main criterion for inclusion
      was the isolation of Mycobacterium tuberculosis from a bone marrow specimen.
      RESULTS: We identified 22 patients with culture-proven M. tuberculosis infection
      of the bone marrow. Underlying conditions found in this series include solid
      organ transplantation in 4 patients (18%), HIV infection in 2 (9%), and diabetes
      in 3 (14%). No risk factor was identified in 12 patients (55%). Histopathological
      findings were reported as granuloma in 19 patients (86%) and caseating granuloma
      in 3 (14%). The outcome was favourable for 11 patients (50%), while 10 (45%) died
      during hospitalisation and one was lost to follow-up. For patients who completed
      their regimens, the duration of treatment was 12 months. CONCLUSION: The
      isolation of M. tuberculosis from a bone marrow specimen is an indication of
      disseminated disease which carries a high mortality rate and requires prompt
      initiation of appropriate treatment.

PMID- 16964799
TI  - An algorithmic approach to female genital tuberculosis causing infertility.
AB  - SETTING: A private infertility care and in vitro fertilisation (IVF) centre in
      Northern India. OBJECTIVES: To describe the prevalence, clinical spectrum,
      management strategy and outcome of infertility due to female genital tuberculosis
      (GTB) diagnosed with the help of a simplified tuberculosis (TB) algorithm.
      DESIGN: Data from 150 women with infertility (Group I) and 47 women with general
      gynaecological problems (Group II) were analysed. RESULTS: GTB was diagnosed in
      7.2% of Group I and 2.8% of Group II women. Anti-tuberculosis treatment resulted
      in resolution of symptoms other than infertility in over 90% of cases. Of the
      total 20 pregnancies in the group, 10 were obtained in 32 IVF treatment patients.
      CONCLUSIONS: A definitive bacteriological diagnosis was generally difficult to
      achieve in GTB before administration of anti-tuberculosis treatment. A high index
      of suspicion and several other morphological and/or laboratory criteria were
      employed. It is suggested that a step-wise algorithm can help in the management
      of these cases.

PMID- 16964800
TI  - Transmission of Mycobacterium tuberculosis from an infant.
AB  - SETTING: This report investigates the unusual transmission of Mycobacterium
      tuberculosis from a 12-week-old infant with nosocomially acquired tuberculosis
      (TB). Compliance with recommendations on the post-exposure management of young
      children is described. DESIGN: Contacts of an infant case of TB were identified
      and recommended to undergo baseline and post-exposure tuberculin skin tests (TST)
      as per Canadian TB standards. TST conversion was measured at least 8 weeks post
      exposure. Children aged <6 years were recommended to initiate preventive
      treatment with isoniazid (INH) until their post-exposure TST. Information on TST
      results and adherence to therapy were analysed from existing medical records.
      RESULTS: Overall, 17 TST conversions were documented among 732 contacts: both
      parents, two health care workers (HCWs) who provided close care, and several
      patients, visitors and one staff member without obvious close contact. Of 65
      eligible children, 46% completed post-exposure therapy as recommended. The most
      common reasons for treatment failure were concern about side effects, perception
      of low risk and lack of physician support. CONCLUSION: This investigation
      suggests that all children, including infants, with cough and numerous bacilli or
      extensive pulmonary disease should be considered infectious. Health care provider
      education is necessary to resolve the observed low compliance with current post
      exposure management guidelines.

PMID- 16964801
TI  - Application of the Genotype MTBDR assay directly on sputum specimens.
AB  - The Genotype MTBDR assay was tested for its capability to detect rifampicin (RMP)
      and isoniazid (INH) resistance (r) and susceptibility (s) directly from 42 smear
      positive sputum specimens (15 RMPr/INHr, 2 RMPs/INHr and 25 RMPs/INHs
      Mycobacterium tuberculosis complex strains). The concordance between the MTBDR
      assay and conventional drug susceptibility testing was 100%.

PMID- 16964802
TI  - Light emitting diodes for auramine O fluorescence microscopic screening of
      Mycobacterium tuberculosis.
AB  - We describe the simple adaptation of a standard fluorescent microscope for
      illumination using a 'Royal Blue' Luxeon light emitting diode (LED) and
      demonstrate that this form of illumination is suitable for the detection of
      auramine O stained Mycobacterium spp. The low cost, low power consumption, safety
      and reliability of LEDs makes them attractive alternatives to mercury vapour
      lamps.

PMID- 16964803
TI  - 6-month treatment for bone tuberculosis.

PMID- 16964804
TI  - Refocus on the stability and quality of anti-tuberculosis formulations.

PMID- 16964805
TI  - Pride or prejudice: an insight into surgical mentality.

PMID- 16964806
TI  - Sinistral portal hypertension.
AB  - Sinistral, or left-sided, portal hypertension is a rare cause of upper
      gastrointestinal haemorrhage. There are many causes of sinistral portal
      hypertension. The primary pathology usually arises in the pancreas and results in
      compression of the pancreatic vein. This compression causes backpressure in the
      left portal venous system and subsequent gastric varices. Management is usually
      surgical to treat the underlying pathology and splenectomy to decompress the left
      portal venous system. This paper presents four cases of sinistral portal
      hypertension followed by a literature review of the reported causes and
      management issues.

PMID- 16964807
TI  - The winged chariot and the iron cages.

PMID- 16964808
TI  - The emerging pattern of hydrops fetalis--incidence, aetiology and management.
AB  - OBJECTIVES: To analyse the incidence, aetiology and management of live born cases
      of hydrops fetalis in a Regional Perinatal Centre. METHODS: We reviewed 35 cases
      of hydrops delivered over a six year period. RESULTS: Non-immune hydrops
      accounted for 80% of the cases and the majority of babies required Level 1
      intensive care. The mortality rate was 40%. CONCLUSION: The pattern of hydrops is
      changing. Most of these babies now have non-immune hydrops and approximately two
      thirds are surviving.

PMID- 16964809
TI  - Substance abuse in pregnancy: opioid substitution in a northern Ireland maternity
      unit.
AB  - An increase in illicit drug use in Northern Ireland may well have links to the
      resolution of political conflict, which started in the mid 1990s. Social issues,
      heretofore hidden, have emerged into the limelight and may be worsened by
      paramilitary involvement. Registered addicts in the four Health Board areas have
      shown an increase from 1997 with the greatest number resident within the Northern
      Board Area. As the prevalence of heroin use in Northern Ireland increased, the
      Department of Health and Social Services and Public Safety (DHSSPS) commissioned
      a report, to recommend the development of substitute prescribing services. A case
      series of pregnancies was reviewed, within the Northern Board Area, where the
      mother was taking opioid substitution therapy. This resulted in baseline data of
      outcome for both mother and baby specific to a Northern Ireland population. The
      different medications for opioid substitution are also assessed. This information
      will guide a co-ordinated approach that involves obstetrician, anaesthetist,
      psychiatrist, midwife and social worker to the care of these high-risk
      pregnancies. Eighteen pregnancies were identified in the study period. Sixteen of
      these had viable outcomes. One was a twin pregnancy. Outcome data was therefore
      available for 17 infants. Information was obtained regarding patients' social and
      demographic background, drug taking behaviour and substitution regimen. Antenatal
      and intrapartum care was assessed and infants were followed up to the time of
      hospital discharge.

PMID- 16964810
TI  - Atypical Mycobacterial infections in children: the case for early diagnosis.
AB  - BACKGROUND & AIMS: Atypical Mycobacteria (ATB) are a miscellaneous collection of
      Mycobacteriaceae which also includes M. tuberculosis, M. bovis and M. leprae. In
      the paediatric population, ATB infections present with non-tender unilateral
      lymphadenopathy in a systemically well child. Initially the disease may be
      mistaken for a staphylococcal or streptococcal abscess. Inappropriate surgical
      incision and drainage is often performed and specimens may be sent for routine
      histopathology and bacteriology analysis only without considering Mycobacterial
      infection. The simple incision and drainage procedures can complicate the
      management and may result in a poor cosmetic outcome. ATB can go undiagnosed
      until the initial medical management has failed, these surgical interventions
      performed and the child remains symptomatic. We wish to highlight the importance
      of considering ATB infection in the differential diagnosis of a child with
      painless lymphadenitis. METHODS: An illustrative case report is described. A
      review of the paediatric data from the Mycobacterial laboratories in Northern
      Ireland over the last 14 years was performed to ascertain disease trends and
      prevalence of species. RESULTS: Overall an upward trend in the number of cases of
      cervical lymphadenitis caused by ATB infections in children was demonstrated.
      Organisms isolated in our population were M avium intracellulare, M malmoense and
      M interjectum. CONCLUSIONS: We would like to present this data and a literature
      review, illustrated by case report, on the optimal management of these
      infections. We suggest that early definitive surgery is the management of choice,
      performed ideally by a surgeon with experience of this condition. A heightened
      awareness of these infections is essential to ensure appropriate early
      management.

PMID- 16964811
TI  - Addressing a community's cancer cluster concerns.
AB  - The felling of a telecommunications mast highlighted a community's concern
      regarding an alleged cancer cluster of eleven cases in a small rural area of
      Northern Ireland. At the request of the Local District Council, the Northern
      Ireland Cancer Registry (NICR) undertook an investigation. After extensive
      searching and contact with the community, only 6 of the alleged cases could be
      identified. Of these six, two did not have cancer and one had a non-malignant
      tumour. In addition to the three confirmed cancer cases, a search of the NICR
      database identified a further 17 cancers of mixed types in keeping with the
      population pattern of cancers. Standardised incidence and mortality rates were
      within, or lower than, the expected level. The results were presented to the
      local community at an open meeting. Despite extensive media interest when the
      issue of the alleged cluster was first raised, the negative findings received
      only local media attention. This study illustrates the value of an accurate
      population cancer registry in addressing cancer cluster concerns.

PMID- 16964812
TI  - Outcome following proximal femoral fracture in Northern Ireland.
AB  - OBJECTIVE: To study the outcome following treatment for proximal femoral fracture
      in elderly people. METHODS: All consecutive males and females admitted to the
      acute fracture service at the Royal Victoria Hospital and the Belfast City
      Hospital for the 3 years from 1999 to 2001 were studied. The data was collected
      by trained research nurses. Variables gathered included age, sex, marital status,
      mental state, pre-injury Barthel score and the American Society of
      Anaesthesiology (ASA) physical status grading. The information was gathered on
      admission to hospital and at four, six and 12 months after the injury. RESULTS:
      The total number of patients studied between January 1999 to December 2001 was
      2834 of whom 77% were female and 23% were male. The mean (median) length of stay
      in the acute fracture service was 10.7 (9 days). The mean (median) length of stay
      in the rehabilitation ward was 35.3 (24 days). The 30-day mortality was 6.9%, the
      four-month mortality 15.6 % and one year mortality 22.3 %. Of those subjects
      living at home at the time of fracture 68% remained at home at one year. Factors
      predicting successful return home were higher mental test score, younger age,
      female sex, higher Barthel score, better pre-injury mobility and better ASA
      score. Of those able to walk independently outdoors before injury 40% regained
      this ability by 12 months. Factors predicting return of pre-injury mobility were
      poorer pre-injury mobility, younger age, higher mental test score, better ASA
      category, higher Barthel score, and previous residence at home. The proportion
      admitted from their own home and discharged by 56 days was 56%. CONCLUSION: The
      standardised measurement of outcome in hip fracture subjects enables comparison
      between units and facilitates improvement in standards of care available to the
      increasing number of elderly patients presenting with proximal femoral fracture.

PMID- 16964813
TI  - The Ulster Medical Society's bust of James McDonnell.

PMID- 16964814
TI  - The 200th anniversary of the founding of the Belfast Medical Society.

PMID- 16964815
TI  - Two hundred years of midwifery 1806-2006.

PMID- 16964816
TI  - Extra salivary adenoid cystic carcinoma; report of two cases.

PMID- 16964817
TI  - Trichosporon asahii. Blood-stream infection in a non-cancer patient receiving
      combination antifungal therapy.

PMID- 16964818
TI  - Laparoscopic removal of abdominal cervical suture.

PMID- 16964819
TI  - Cerebral abscess in a 16 year old boy.

PMID- 16964820
TI  - The changing face of general practice in Northern Ireland--Portfolio GP's.
      Interview by Claire T Lundy.

PMID- 16964821
TI  - Genomics of hepatitis B and C infections: diagnostic and therapeutic applications
      of microarray profiling.
AB  - Microarray profiling offers many potential advances in diagnostic and therapeutic
      intervention in human disease because of its unparalleled ability to conduct high
      throughput analysis of gene expression. However, limitations of this technique
      relate in part to issues regarding the various methodologies and experimental
      designs as well as difficulties in the interpretation of results. Despite this,
      microarray profiling has led to a better understanding of the molecular
      pathogenesis of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection.
      Key events in clearance and the development of chronicity of HCV have been
      identified that may prove to have a role in the development of future treatments.
      In addition, pharmacogenomic studies of interferon-based treatment for chronic
      HCV and HBV have provided mechanistic insights into the therapeutic action of
      interferons. These advances have implications with respect to the development of
      improved therapeutic agents. New biomarkers for cancer screening and gene
      profiles with prognostic value for survival have also been developed for
      hepatocellular carcinoma, which frequently complicates chronic viral hepatitis.
      Thus, microarray profiling offers enormous potential for improvements in
      antiviral therapy and our understanding of blood-borne viral hepatitis.

PMID- 16964822
TI  - Drug-class-wide resistance to antiretrovirals in HIV-infected patients failing
      therapy: prevalence, risk factors and virological outcome.
AB  - BACKGROUND: Drug-class-wide resistance (DCWR) to antiretrovirals substantially
      reduces treatment options. METHODS: A database of 602 patients failing highly
      active antiretroviral therapy (HAART) undergoing genotypic resistance test (GRT)
      was analysed. DCWR was defined according to the International AIDS Society
      consensus. A multiple logistic regression model was built to define factors
      significantly associated with DCWR and to assess virological response to salvage
      regimens. RESULTS: NRTI DCWR was observed in 28.5% of 592 NRTI-exposed patients,
      NNRTI DCWR in 57.7% of 284 NNRTI exposed patients, PI DCWR in 19.9% of 412 PI
      exposed patients, and three-class resistance in 21.4% of 112 three-class-exposed
      patients. The prevalence of NRTI and PI DCWR increased significantly by year of
      exposure to the same class from 8.9% (< 1 year) to 35.3% (> 4 years) and from
      1.2% (< 1 year) to 34.8% (> 4 years), respectively (P < 0.001, for trend). The
      risk of developing NRTI and PI DCWR increased by 25% (95% confidence interval
      [CI]: 1.6%-51.3%) and by 53% (20.5%-94.3%) for each year of treatment, and by 17%
      (95% CI: 5.6%-29.3%) and by 32% (17.7%-50.3%) for each previous failing NRTI- and
      PI-containing regimen, respectively. NRTI DCWR due to at least four nucleoside
      analogues mutations (NAMs) increased by year of NRTI exposure from 8.9% (< 1
      year) to 32.6% (> 4 years; P < 0.001, for trend). After adjustment for
      confounding factors, the probability of achieving plasma viral load < 500
      copies/ml was significantly reduced in patients with NRTI (OR: 0.750; 95% CI:
      0.574-0.979), NNRTI (OR: 0.746; 95% CI: 0.572-0.975), PI (OR: 0.655; 95% CI:
      0.456-0.941), three-class (OR: 0.220; 95% CI: 0.082-0.593) resistance.
      CONCLUSIONS: The probability of developing NRTI and PI DCWR increased with length
      of class exposure and with the number of previously failing regimens. By
      contrast, high levels of NNRTI DCWR were observed within 1 year in NNRTI-failing
      patients, with a steady prevalence over time. The increase in prevalence with
      time of NRTI DCWR was due to the accumulation of NAMs. DCWR to NRTIs, NNRTIs, PIs
      or all the three together was associated with an increased probability of
      virological failure to subsequent HAART regimens.

PMID- 16964823
TI  - Foscarnet salvage therapy for patients with late-stage HIV disease and multiple
      drug resistance.
AB  - OBJECTIVE: To evaluate the efficacy of foscarnet on HIV infection in patients
      with late-stage HIV disease and multiple drug resistance. METHODS: Three drugs
      experienced patients with plasma viral load (pVL) > 50,000 copies/ml and CD4+ T
      cell counts < 100/mm3 were eligible for this open-label, single-arm, add-on pilot
      study. Foscarnet induction therapy consisted of 5 g intravenously twice daily for
      6 weeks, in addition to a stable antiretroviral regimen. Patients with at least 1
      log10 decrease in pVL at week 6 (W6), were given foscarnet 5 g intravenously
      twice daily on two consecutive days each week. Primary endpoint was the
      virological response rate at W6. RESULTS: Eleven patients were enrolled with a
      median baseline pVL at 5.16 log10 copies/ml, median CD4+ T-cell count at 10/mm3
      and median number of mutations of 9, 2 and 12 associated with resistance to
      nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs and protease
      inhibitors, respectively. One patient discontinued foscarnet at W2 because of
      renal toxicity. In an intent-to-treat analysis, the median change in pVL from
      baseline was -1.99 log10 copies/ml at W2 and -1.79 log10 copies/ml at W6. Eight
      out of eleven patients had a fall in pVL of at least 1 log10 at W6, and six
      started maintenance therapy. The median fall in pVL after 12 weeks of maintenance
      therapy was -0.85 log10 copies/ml in the four patients who reached W12, and the
      median increase of CD4+ T-cell count was 60/mm3. CONCLUSION: In patients with HIV
      mutations conferring resistance to all antiretroviral drug classes, foscarnet
      markedly reduced plasma HIV load and improved immunological status.

PMID- 16964824
TI  - Impact of lamivudine on the risk of liver-related death in 2,041 HBsAg- and HIV
      positive individuals: results from an inter-cohort analysis.
AB  - BACKGROUND: The impact of lamivudine (3TC) as part of combination antiretroviral
      therapy (cART) on the risk of liver-related death (LRD) in HIV/hepatitis B virus
      (HBV)-coinfected patients has not been extensively studied. METHODS: We performed
      an analysis involving HIV/HBV-coinfected patients in 13 cohorts who initiated
      cART. The end-point was LRD--that is, death with concomitant decompensated liver
      disease (DLD) or hepatocellular carcinoma--as the main cause. Incidence rates of
      LRD after initiation of cART were expressed as number of events per 100 person
      years of follow-up (PYFU). A Poisson regression model adjusted for cohort,
      gender, mode of HIV transmission, CD4+ T-cell count at cART initiation, liver
      disease pre-cART, duration of 3TC before cART, and hepatitis C virus was used to
      assess the association between use of 3TC and risk of LRD. RESULTS: We analysed
      2,041 patients. Follow-up after starting cART was 7,648 PYFU (5,569 spent on 3TC
      containing regimens) with a median per person of 48 months (range: 2-91). Of the
      total, 217 subjects died; 57 deaths were liver-related resulting in a rate of 7.5
      per 1,000 PYFU [95% confidence intervals (CI): 5.6-9.7]. The relative risk of LRD
      per extra year of 3TC use was 0.73 (95% CI: 0.59-0.90, P = 0.004). CONCLUSION:
      The use of 3TC was associated with a reduced risk of LRD over 4 years of follow
      up. This study supports the current view that the use of 3TC as part of cART
      should be considered in patients who are tested positive for HBsAg.

PMID- 16964825
TI  - HIV-1 drug-resistance mutations among newly diagnosed patients before scaling-up
      programmes in Burkina Faso and Cameroon.
AB  - We analysed whether mutations associated with resistance to antiretroviral (ARV)
      drugs circulate among treatment-naive HIV-1-infected individuals at a period when
      these drugs started to become more widely available in Africa. Overall, major
      resistance mutations in the pol gene, as defined by the International AIDS
      Society Resistance Testing-USA panel, were observed in 16 treatment-naive
      individuals. Eight of the 97 patients tested in Burkina Faso bore mutations
      conferring resistance to one drug class of ARV drugs: two to nucleoside reverse
      transcriptase inhibitors (NRTIs; M41L [n = 1], M41L+T69S [n = 1]), four to non
      NRTIs (NNRTIs; V106A/V [n = 1] and V1081 [n = 3]) and two to protease inhibitors
      (PIs; L33F [n = 2]). In Cameroon, resistance mutations were identified in 8 of
      102 patients: three to PIs (M461/L [n = 2], L33F [n = 1]), three to NRTIs (T69N/T
      [n = 1], M184V [n = 1], A62V [n = 1]) and two to NNRTIs (P236L [n = 1], V1081 [n
      = 1]). It is important to note that not all genotypic drug-resistance algorithms
      give similar interpretations to the observed mutations. Population surveillance
      for ARV drug resistance is required and should be included in all implementation
      programmes.

PMID- 16964826
TI  - Investigation of baseline susceptibility to protease inhibitors in HIV-1 subtypes
      C, F, G and CRF02_AG.
AB  - OBJECTIVE: To compare baseline susceptibility to protease inhibitors among HIV-1
      isolates of subtypes C, F, G and CRF02_AG, and to identify polymorphisms that
      determine the differences in susceptibility. METHODS: A total of 42 samples of
      drug-naive patients infected with subtypes G (n=19), CRF02_AG (n = 10), F (n = 6)
      and C (n = 7) were phenotyped and genotyped with the Antivirogram and the ViroSeq
      2.0 genotyping system, respectively. A Bayesian network approach was used for a
      preliminary analysis of the collected data and the dependencies indicated by the
      network were statistically confirmed. RESULTS: CRF02_AG samples were found to be
      more susceptible to nelfinavir and ritonavir than other subtypes.
      Hypersusceptibility to these drugs was associated with the 70R polymorphism.
      37D/S/T was associated with reduced susceptibility to indinavir and 89M with
      reduced susceptibility to lopinavir. Susceptibility to tipranavir was the lowest
      among the subtype F samples and the highest for subtype G samples, with samples
      carrying 57R being more susceptible than samples carrying 57K. CONCLUSIONS: Our
      study suggests that there are baseline susceptibility differences between
      subtypes and these differences are due to naturally occurring polymorphisms in
      these subtypes. The predictive value for phenotype of these polymorphisms was
      even valid in subtypes where these polymorphisms are less prevalent. Taking into
      account such polymorphisms should improve current algorithms for interpretation
      of genotyping results in a subtype-independent way.

PMID- 16964827
TI  - Declining prevalence of HIV-infected individuals at risk of transmitting drug
      resistant HIV in Denmark during 1997-2004.
AB  - BACKGROUND: Transmission of drug-resistant HIV is a potential threat to the
      substantial clinical benefit of highly active antiretroviral therapy (HAART). To
      explore the background for the low rates of drug resistance transmission (2.5%)
      in our population, we estimated acquisition of HIV drug resistance and examined
      temporal trends in the prevalence of patients at risk of transmitting drug
      resistant HIV. METHODS: The study population included all 4,025 patients from The
      Danish HIV Cohort Study seen during the period 1995-2004. Virological failure to
      a given drug class was defined as a viral load (VL) > 1,000 copies/ml for 120
      days while on a HAART regimen including that drug class. In addition, receiving
      nucleoside reverse transcriptase inhibitors (NRTIs) for 180 days before HAART
      counted as NRTI failure irrespective of VL. Having experienced failure was
      considered a proxy for harbouring drug-resistant virus in subsequent observation
      time. Patients with a current VL > 1,000 copies/ml were considered at risk of
      transmitting HIV. RESULTS: We found a decrease from 1997 to 2004 in the
      prevalence of potential transmitters of drug-resistant HIV. The number of these
      patients with previous NRTI failure decreased from 429 (24% of all patients) in
      1998 to 213 (8.0% of all patients) in 2004. Previous protease inhibitor (PI)
      failure peaked at 279 (14%) in 1999, declining to 142 (5.3%) in 2004. Previous
      NNRTI failure peaked at 121 patients (4.7%) in 2002, and occurred in 113 patients
      (4.2%) in 2004. Of all 686 potential transmitters in 2004, 31% had previously
      experienced NRTI failure, 21% PI failure, and 16% non-NRTI failure. CONCLUSION:
      In the population of HIV-infected individuals in Denmark with complete follow-up,
      the number at risk of transmitting drug-resistant virus declined over time.

PMID- 16964828
TI  - Mitochondrial (mt)DNA changes in tissue may not be reflected by depletion of
      mtDNA in peripheral blood mononuclear cells in HIV-infected patients.
AB  - OBJECTIVES: Most data on mitochondrial toxicity have been derived from peripheral
      blood mononuclear cells (PBMCs). However, whether mitochondrial DNA (mtDNA)
      content in PBMCs reflects the mitochondrial state in tissues remains elusive. We
      report herein on mitochondrial toxicity in skeletal muscle in HIV-infected
      patients naive to antiretroviral treatment (ART [HIV+ART-naive]; n = 10) patients
      exposed to nucleoside reverse transcriptase inhibitors (NRTIs [HIV+NRTI+]; n =
      24) and healthy controls (n = 11), and compare these tissue data with mtDNA in
      PBMCs. METHODS: Muscle biopsies were examined for (i) mtDNA and nuclear DNA
      (nDNA) content using TaqMan real-time PCR system, (ii) mtDNA deletions using long
      expand PCR with subsequent gel electrophoresis, and (iii) mitochondrial myopathy
      expressed as cytochrome c oxidase (COX)-deficient muscle fibres. RESULTS: The
      mt/n DNA ratio in muscle from HIV+NRTI+ patients was reduced compared with HIV
      negative controls (P = 0.028). Moreover, mtDNA deletions were more frequent in
      HIV+NRTI+ patients than in both HIV-negative controls (P = 0.009) and HIV+ART
      naive patients (P = 0.005). HIV+NRTI+ also tended to have more COX-deficient
      fibres than HIV-negative controls (P = 0.076). COX-deficient fibres were
      positively correlated with mtDNA deletions in HIV+NRTI+ patients (r = 0.83, P <
      0.001). Patients with current use of didanosine (ddl) had more frequent mtDNA
      deletions and COX-deficient fibres than HIV+NRTI+ not on current treatment with
      ddl. It should be noted that mitochondrial alterations were not correlated with
      mtDNA/cell in PBMCs in any group. CONCLUSIONS: In skeletal muscle, HIV+NRTI+ had
      a reduced mt/n DNA ratio, more frequent mtDNA deletions and possibly more COX
      deficient muscle fibres than HIV-negative controls. However, the mtDNA/cell in
      peripheral blood was decreased in both HIV+NRTI+ and HIV+ART-naive patients.
      Thus, mtDNA in peripheral blood may not be a relevant marker of mitochondrial
      toxicity in organ-specific tissue.

PMID- 16964829
TI  - Lopinavir/ritonavir or efavirenz plus two nucleoside analogues as first-line
      antiretroviral therapy: a non-randomized comparison.
AB  - BACKGROUND: Although efavirenz (EFV) and lopinavir/ ritonavir (LPV/r) are both
      recommended antiretroviral agents for combination therapy in drug-naive HIV
      infected patients, no randomized comparison of their efficacy and tolerability is
      available yet. A multi-cohort prospective observational comparative study was
      performed. METHODS: Efficacy was examined comparing time to virological failure,
      CD4 recovery and clinical progression. Tolerability was examined comparing time
      to treatment discontinuation for any reason and for toxicity and time to liver
      enzymes or lipid alterations. Survival analysis was conducted by an intent-to
      treat principle using the Kaplan-Meier method, and standard and weighted Cox
      regression models. RESULTS: A total of 674 antiretroviral-naive patients starting
      a two nucleoside reverse transcriptase inhibitor regimen plus either EFV (n =
      481) or LPV/r (n = 193) were examined. At baseline, patients starting LPV/r had
      higher HIV RNA and lower CD4+ T-cell counts. There was no difference in the
      adjusted hazards of virological failure (LPV/r versus EFV relative hazard [RH]
      1.16, 95% confidence intervals [CI]: 0.58-2.32, P = 0.67), CD4 recovery (RH =
      0.93, 95% CI: 0.66-1.30, P = 0.66), clinical progression (RH = 1.64, 95% CI: 0.70
      3.84, P = 0.25), drug discontinuation for toxicity (RH = 0.92, 95% CI: 0.51-1.64,
      P = 0.76) and for any reason, and rates of liver enzyme and total/low density
      lipoprotein (LDL) cholesterol elevation. In contrast, the rate of triglycerides
      elevations (> 1 NCEP Adult Treatment Panel III category increase) was higher in
      the LPV/r group (RH = 1.69, 95% CI: 1.14-2.50; P = 0.01). Models weighted for the
      inverse of conditional probability of receiving either drug applied to the
      efficacy endpoints yielded similar results. CD4 recovery with both drugs was also
      similar in the lowest CD4 strata. CONCLUSIONS: Our analysis suggests similar
      efficacy and tolerability for EFV- or LPV/r-based first-line antiretroviral
      regimens. LPV/r was associated with higher rates of hypertriglyceridaemia.

PMID- 16964830
TI  - Amdoxovir versus placebo with enfuvirtide plus optimized background therapy for
      HIV-1-infected subjects failing current therapy (AACTG A5118).
AB  - BACKGROUND: Amdoxovir (2,6-diaminopurine dioxolane; DAPD) is a nucleoside reverse
      transcriptase inhibitor (NRTI) of human immunodeficiency virus-1 (HIV-1) with
      activity against wild-type and NRTI-resistant viruses. METHODS: ACTG A5118
      assessed the antiretroviral activity and safety of DAPD (300 mg orally, twice
      daily) versus placebo in combination with enfuvirtide (ENF) plus an optimized
      background (OB) regimen in subjects with failure of two or more antiretroviral
      (ARV) regimens. The primary endpoints for comparison were time-averaged area
      under the curve minus baseline (AAUCMB) of plasma HIV-1 RNA concentration at 24
      weeks and time to first serious (DAIDS toxicity table Grade > or = 3) adverse
      event (AE). An unplanned interim review recommended closing enrollment because
      the study was unlikely to demonstrate a difference between arms. The 18 subjects
      on study, nine in each arm, were unblinded and allowed to continue study
      treatment through 48 weeks. RESULTS: Intention-to-treat analysis showed the
      median AAUCMB was -0.9 log10 copies/mL (95% CI = -2.2, -.0.1) in the DAPD arm and
      -0.9 log10 copies/ml (95% CI = -1.1, -0.1) in the placebo arm (P = 0.69). Median
      CD4+ T-cell increase was 79 cells/mm3 (95% CI =1, 115) in the DAPD arm and 60
      (95% CI =1, 101) in the placebo arm (P = 0.45). Time to first serious AE did not
      differ between arms (P = 0.91). Mild decreases of creatinine clearance were
      observed with similar frequency between arms; no subject developed lens
      opacities. CONCLUSIONS: Addition of DAPD to ENF plus OB in advanced subjects with
      highly resistant virus appeared safe, but did not add statistically significant
      antiretroviral activity at 24 weeks in this small study.

PMID- 16964831
TI  - Short communication metabolic and mitochondrial effects of switching
      antiretroviral-experienced patients to enfuvirtide, tenofovir and
      saquinavir/ritonavir.
AB  - OBJECTIVE: Investigate the metabolic and mitochondrial effects of switching a
      highly active antiretroviral therapy (HAART) regimen with a high mitochondrial
      toxicity profile to a HAART with a theoretically low mitochondrial toxicity.
      PATIENTS AND METHODS: Six consecutive HAART-experienced patients receiving at
      least one dideoxy-nucleoside reverse transcriptase inhibitor (NRTI) switched to
      enfuvirtide plus tenofovir plus saquinavir/ritonavir (T20+TDF+SQV/r). Blood
      samples were collected at baseline, 12 and 24 weeks after the switch, and viral
      load (VL) and lymphocyte CD4+ T-cell count were determined. Metabolic parameters
      consisted of fasting serum triglycerides, cholesterol (total and fractions),
      glucose, insulin, C-peptide and lactate. Mitochondrial assessment consisted on
      mitochondrial DNA (mtDNA) quantification, COX-II mitochondrial protein expression
      rate, mitochondrial respiratory chain complex III and IV activities, and oxygen
      consumption in peripheral blood mononuclear cells. For baseline mitochondrial
      comparisons, we included six HIV-infected patients naive for ART. RESULTS:
      Switched patients exhibited a mean increase of 26 CD4+ T-cells/mm3 and a mean
      decrease of 1.1 log in VL (P = NS for both). Lactate, lipids and glycaemia
      remained stable during the study; only insulin levels increased significantly (P
      < 0.05). Switched patients exhibited, at baseline, low mitochondrial
      measurements, being significant only for complex III and IV activities with
      respect to naive patients (P < 0.05 for both). MtDNA content did not rise
      significantly during the study. However, we observed increases in COX-II
      mitochondrial protein synthesis (124%, P < 0.05), complex III activity (127%, P <
      0.05), complex IV activity (86%, P = 0.37) and oxygen consumption (194%, P <
      0.05). CONCLUSION: Switching a HAART-containing dideoxy-NRTI to T20+TDF+SQV/r
      minimally alters metabolic parameters and exerts beneficial effects on
      mitochondrial function at 24 weeks. Mitochondrial improvement should be
      considered as an additional advantage of this rescue therapy.

PMID- 16964832
TI  - Absence of resistance mutations in antiretroviral-naive patients treated with
      ritonavir-boosted saquinavir.
AB  - BACKGROUND: There are few data on the selection of resistance by ritonavir
      boosted saquinavir (SQV/r), particularly in antiretroviral (ARV)-naive patients.
      OBJECTIVE: To assess the incidence of virological failure and evolution of
      resistance in ARV-naive individuals receiving SQV/r in the induction phase of the
      Staccato trial. METHODS: ARV-naive subjects (n = 272) received SQV/r 1,600/100 mg
      once daily with two nucleoside reverse transcriptase inhibitors (NRTIs) for at
      least 24 weeks. Patients were defined as having virological failure (VF) when
      there were two consecutive HIV-1 RNA measurements > 500 copies/ml after week 12.
      Viral genotypes (reverse transcriptase [RT] and protease [PRO]) were determined
      at baseline in all patients and as close as possible to the time of initial
      failure in patients experiencing VF. RESULTS: VF was observed in 9/272 patients
      receiving SQV/r 1,600/100 mg once daily with two NRTIs (3.3%) and occurred 19-48
      weeks after treatment initiation. Eight of these patients were evaluable at
      failure. No major PRO mutations were detected, but 2/8 displayed single new minor
      PRO substitutions (M36I, L10I) at VF that were known or suspected not to have
      been present at baseline; both these substitutions exist as natural
      polymorphisms. A third patient displayed a single new RT mutation (M184I).
      CONCLUSIONS: SQV/r plus two NRTIs (1,600/100 mg once daily) is an effective
      initial treatment option for ARV-naive patients, resulting in a low rate of viral
      rebound (3.3%). Furthermore, no major protease mutations were detected following
      VF, suggesting that future treatment options are preserved.

PMID- 16964833
TI  - Defective synthesis of granulocyte-colony stimulating factor in pegylated
      interferon-alpha treated chronic hepatitis C patients with declining leukocyte
      counts.
AB  - BACKGROUND: Pegylated-interferon-alpha (peg-IFN-alpha) is the mainstay of
      treatment for chronic hepatitis C (CHC). Treatment is often complicated by
      neutropaenia due to inhibition of haematopoiesis. However, there are no data on
      the kinetics of granulocyte-colony stimulating factor (G-CSF), a major neutrophil
      growth factor, in this setting. We therefore evaluated G-CSF synthesis in CHC
      patients on peg-IFN-alpha treatment. METHODS: A total of 40 CHC patients were
      studied. None had pre-existing haematological disorders, or hepatitis B virus or
      HIV coinfection. For controls, 30 healthy subjects were used. Laboratory
      examinations, including liver function tests, were performed at baseline and
      monthly over treatment and follow-up. Serum G-CSF was measured in all patients
      and controls at baseline and in a subgroup of 20 CHC patients also at weeks 2, 4,
      24, 48 and 72 after treatment start. RESULTS: CHC patients had a significantly
      lower pre-treatment neutrophil count (3,256 +/- 1,197 versus 3,804 +/- 859; P =
      0.03). Notwithstanding, they showed lower baseline G-CSF serum levels than
      healthy controls (16.1 +/- 6.2 versus 19.4 +/- 7.5; P = 0.048). Consistently,
      baseline G-CSF levels were poorly correlated with the neutrophil count in CHC
      patients (r = -0.2; P = 0.2). Moreover, serum G-CSF levels did not increase in
      any of the 20 CHC patients during peg-IFN-alpha treatment, despite declining
      neutrophil counts. CONCLUSIONS: The lower neutrophil counts observed in CHC might
      be related to an absolute deficiency in G-CSF production. In the human model of
      neutropaenia induced by peg-IFN-alpha, we show that endogenous G-CSF levels are
      not physiologically up-regulated to overcome the decline in neutrophil counts.
      Our study provides a rationale for the evaluation of recombinant human G-CSF
      treatment in peg-IFN-alpha-induced neutropaenia.

PMID- 16964834
TI  - Does HAART improve renal function? An association between serum cystatin C
      concentration, HIV viral load and HAART duration.
AB  - AIM: The prevalence of renal disease in human HIV-infected individuals varies
      between 2% and 10%. Many reports have demonstrated the beneficial effect of
      antiretroviral (ARV) therapy on slowing the progression of renal diseases. The
      aim of our cross-sectional study was to determine serum cystatin C concentration
      in different stages of HIV infection and the relationship between cystatin C
      concentration and ARV treatment. METHODS: Cystatin C concentration was measured
      in the sera of 77 HIV-1-infected individuals and 18 HIV-seronegative volunteers.
      The glomerular filtration rate (GFR) was estimated using the Modification of Diet
      in Renal Disease Study formula. RESULTS: HIV infection resulted in a significant
      increase in serum cystatin C concentration compared with healthy individuals
      (933.4 +/- 32.1 vs 621.1 +/- 56.8 ng/ml, P < 0.001). There were no significant
      differences in urea, creatinine and GFR between those groups. On multivariate
      analyses serum cystatin C was independently associated with highly active
      antiretroviral therapy (HAART) duration (beta = -0.34, P = 0.04) and HIV viral
      load (beta = 0.33, P = 0.04), whereas there were no significant relationships
      with age, body mass index, HIV duration, CD4+ and CD8+ T-cell counts and serum
      high sensitivity C-reactive protein concentration. CONCLUSIONS: Our initial
      observations indicate that serum cystatin C, which may reflect mild renal
      dysfunction, is increased during HIV-infection and is associated with HIV viral
      load. Long-lasting HAART seems to decrease cystatin C concentration, thus
      potentially improves renal function.

PMID- 16964835
TI  - Temporary HBV resolution in an HIV-coinfected patient during HBV-directed
      combination therapy followed by relapse of HBV.
AB  - Coinfection of hepatitis B virus (HBV) and HIV is common due to overlapping
      routes of transmission accompanied by an increased risk for liver-related
      mortality. We report the case of a chronically infected hepatitis Be antigen
      positive patient, coinfected with HIV (CD4+ T-cell count > 500 cells/microl),
      with histological evidence of advanced liver disease. The patient developed anti
      HBs (antibody to hepatitis B surface antigen [HBsAg]) seroconversion, a strong
      reduction of intrahepatic covalently closed circular DNA and a marked improvement
      of liver histology after 24 weeks of HBV-targeted combination therapy with
      adefovir dipivoxil and pegylated interferon-alpha2b followed by another 12 weeks
      of adefovir dipivoxil monotherapy. Antiviral therapy was stopped after the
      development of stable anti-HBs titres, and anti-HBs titres remained stable for
      additional 9 months post-treatment. A continuous decline of anti-HBs was observed
      during the next 6 months until anti-HBs disappeared despite a stable HIV
      infection. A triple course of therapeutic vaccination failed to re-establish anti
      HBs antibodies, but reappearance of HBV DNA and HBsAg was detected. By enzyme
      linked immunosorbent spot analyses, HBV-directed T-cell responses clearly
      increased during antiviral combination therapy followed by a reduction to pre
      treatment levels in association with disappearance of anti-HBs antibodies despite
      therapeutic vaccination. The presented case highlights the volatile nature of
      chronic HBV infection even after a prolonged disease-free period in the setting
      of an underlying HIV coinfection in a patient with a stable and relatively high
      CD4+ T-cell count but nevertheless impaired immune system and calls for further
      investigation of probably temporary immunomodulatory effects of interferon-alpha
      and/or nucleoside analogues in immunocompromised patients.

PMID- 16964836
TI  - The XIVth International HIV Drug Resistance Workshop, Quebec City, Canada, June
      2005.
AB  - This report summarizes research advances that further our understanding of the
      evolution, mechanisms and clinical impact of HIV drug resistance presented at the
      XIVth International HIV Drug Resistance Workshop held in Quebec City, Canada from
      June 7-11, 2005. The topics that were discussed included the clinical
      implications of resistance in mother-to-child transmission, breakthroughs in
      technologies for studying resistance, resistance to new antiretroviral agents,
      mechanisms of HIV drug resistance, epidemiological trends, and HIV fitness and
      pathogenesis.

PMID- 16964837
TI  - The cost of dental care.

PMID- 16964838
TI  - All in a day's work.

PMID- 16964840
TI  - Medicine and dentistry.
AB  - Because of the increasing complexity of both medical and dental treatment and the
      numbers of individuals with chronic medical problems, the dentist and physician
      must be aware and knowledgable that many chronic disorders or their treatments
      may manifest in the oral cavity and may have an impact upon both medical and
      dental treatment. These conditions necessitate recognition, diagnosis, and early
      referral as well as alterations in the provision of dental or medical treatment.

PMID- 16964841
TI  - Part one: trends in Minnesota dental practice.

PMID- 16964842
TI  - What's a dentist to do? What are friends for?

PMID- 16964843
TI  - Pandemic preparedness: Y.O.Y.O.

PMID- 16964844
TI  - Point/counterpoint. Within the next five years CT colonography will make
      conventional colonoscopy obsolete for colon cancer screening.

PMID- 16964845
TI  - Efficient x-ray tube simulations.
AB  - This article describes an efficiency study of directional bremsstrahlung
      splitting (DBS) for x-ray tube modeling. DBS is shown to be up to five or six
      orders of magnitude more efficient at 50 or 135 kV tube potential than a
      simulation without splitting, and 60 times more efficient compared to uniform
      bremsstrahlung splitting. A methodology is presented to determine the optimum
      splitting number for a given situation using a second degree polynomial
      expression derived from theoretical considerations. Very large optimum splitting
      numbers are found for small fields (5 mm radius) at 1 m from the x-ray source,
      which are relevant for half-value layer (HVL) calculations and for simulations
      related to primary air kerma standards. Two approaches for the calculation of
      kerma at a plane and inside a volume using track-length estimation are
      implemented in BEAMnrc, a user-code from the EGSnrc Monte Carlo simulation system
      for photon and electron transport. A practical application of DBS to HVL
      calculations for a Comet MXR-320 x-ray tube is reported. The agreement with
      measured HVLs at different constant tube potentials is found to be better than
      2.3%.

PMID- 16964846
TI  - Imaging of joints with laser-based photoacoustic tomography: an animal study.
AB  - Photoacoustic tomography (PAT), a nonionizing, noninvasive, laser-based
      technology was adapted to joint imaging for the first time. Pulsed laser light in
      the near-infrared region was directed toward a joint with resultant ultrasonic
      signals recorded and used to reconstruct images that present the optical
      properties in subsurface joint tissues. The feasibility of this joint imaging
      system was validated on a Sprague Dawley rat tail model and verified through
      comparison with histology. With sufficient penetration depth, PAT realized
      tomographic imaging of a joint as a whole organ noninvasively. Based on the
      optical contrast, various intra- and extra-articular tissues, including skin,
      fat, muscle, blood vessels, synovium and bone, were presented successfully in
      images with satisfactory spatial resolution that was primarily limited by the
      bandwidth of detected photoacoustic signals rather than optical diffusion as
      occurs in traditional optical imaging. PAT, with its intrinsic advantages, may
      provide a unique opportunity to enable the early diagnosis of inflammatory joint
      disorders, e.g., rheumatoid arthritis, and to monitor therapeutic outcomes with
      high sensitivity and accuracy.

PMID- 16964847
TI  - Scanning-beam digital x-ray (SBDX) technology for interventional and diagnostic
      cardiac angiography.
AB  - The scanning-beam digital x-ray (SBDX) system is designed for x-ray dose
      reduction in cardiac angiographic applications. Scatter reduction, efficient
      detection of primary x-rays, and an inverse beam geometry are the main components
      of the entrance dose reduction strategy. This paper reports the construction of
      an SBDX prototype, image reconstruction techniques, and measurements of spatial
      resolution and x-ray output. The x-ray source has a focal spot that is
      electronically scanned across a large-area transmission target. A multihole
      collimator beyond the target defines a series of x-ray beams directed at a
      distant small-area detector array. The prototype has a 23 cm X 23 cm target, 100
      X 100 focal spot positions, and a 5 cm X 5 cm CdTe detector positioned 150 cm
      from the target. With this nonmechanical method of beam scanning, patient images
      with low detected scatter are generated at up to 30 frame/s. SBDX data
      acquisition is tomosynthetic. The prototype simultaneously reconstructs 16 planes
      spaced throughout the cardiac volume using shift-and-add backprojection. Image
      frames analogous to conventional projection images are generated with a
      multiplane compositing algorithm. Single-plane versus multiplane reconstruction
      of contrast-filled coronary arteries is demonstrated with images of the porcine
      heart. Phantom and porcine imaging studies show multiplane reconstruction is
      practicable under clinically realistic levels of patient attenuation and cardiac
      motion. The modulation transfer function for an in-plane slit at mechanical
      isocenter measured 0.41-0.56 at 1 cycle/mm, depending on the detector element to
      image pixel interpolation technique. Modeling indicates that desired gains in
      spatial resolution are achievable by halving the detector element width. The x
      ray exposure rate 15 cm below isocenter, without table or patient in the beam,
      measured 11.5 R/min at 120 kVp, 24.3 kWp and 3.42 R/min at 70 kVp, 14.2 kWp.

PMID- 16964848
TI  - Comparison of entrance exposure and signal-to-noise ratio between an SBDX
      prototype and a wide-beam cardiac angiographic system.
AB  - The scanning-beam digital x-ray (SBDX) system uses an inverse geometry, narrow x
      ray beam, and a 2-mm thick CdTe detector to improve the dose efficiency of the
      coronary angiographic procedure. Entrance exposure and large-area iodine signal
      to-noise ratio (SNR) were measured with the SBDX prototype and compared to that
      of a clinical cardiac interventional system with image intensifier (II) and
      charge coupled device (CCD) camera (Philips H5000, MRC-200 x-ray tube, 72 kWp
      max). Phantoms were 18.6-35.0 cm acrylic with an iohexol-equivalent disk placed
      at midthickness (35 mg/cm2 iodine radiographic density). Imaging was performed at
      15 frame/s, with the disk at mechanical isocenter and an 11-cm object-plane field
      width. The II/CCD system was operated in cine mode with automatic exposure
      control. With the SBDX prototype at maximum x-ray output (120 kVp, 24.3 kWp), the
      SBDX SNR was 107%-69% of the II/CCD SNR, depending on phantom thickness, and the
      SBDX entrance exposure rate was 10.7-9.3 R/min (9.4-8.2 cGy/min air kerma). For
      phantoms where an equal-kVp imaging comparison was possible (> or = 23.3 cm), the
      SBDX SNR ranged from 47% to 69% of the II/CCD SNR while delivering 6% to 9% of
      the II/CCD entrance exposure rate. From these measurements it was determined that
      the relative SBDX entrance exposure at equal SNR would be 31%-16%. Results were
      consistent with a model for relative entrance exposure at equal SNR, which
      predicted a 3-7 times reduction in entrance exposure due to SBDX's comparatively
      low scatter fraction (5.5%-8.1% measured, including off-focus radiation), high
      detector detective quantum efficiency (66%-73%, measured from 70 to 120 kVp), and
      large entrance field area (1.7x - 2.3x, for the same object-plane field width).
      With improvements to the system geometry, detector, and x-ray source, SBDX
      technology is projected to achieve conventional cine-quality SNR over a full
      range of patient thicknesses, with 5-10 times lower skin dose.

PMID- 16964849
TI  - Estimation of radiation dose at various depths for commonly used radionuclides in
      radiosynoviorthesis in a tissue equivalent material.
AB  - The purpose of the paper is to report on the dose estimation studies at various
      depths for the commonly used beta-emitting 90Y, 166Ho, 153Sm, 32p, and 177Lu
      radionuclides in a phantom fabricated using the poly methyl methacrylate tissue
      equivalent material having a density of 1.19 gm/cc, by using thermoluminescent
      dosemeters. GAFChromic MD-55 films were used to calculate the calibration factor
      for the thermoluminescent micro-rods used in our study. It is observed that 90Y
      delivers the highest dose at 1 mm amongst the radionuclides tested followed by
      32p, 166Ho, 153Sm, and 177Lu, whereas the cumulative dose received by the joint
      was found to be more for 32P followed by 90Y, 166Ho, 153Sm, and 177Lu. The
      highest therapeutic range obtained is 3.1 mm for 153Sm amongst the tested
      radionuclides. The dose values obtained for all the above-mentioned radionuclides
      can serve as reference material for those researchers and clinicians who are
      interested in selection of the radionuclide for the type of joint treated and the
      amount of dose necessary to be delivered to the synovial membrane.

PMID- 16964850
TI  - A topographic leaf-sequencing algorithm for delivering intensity modulated
      radiation therapy.
AB  - Topographic treatment is a radiation therapy delivery technique for fixed-gantry
      (nonrotational) treatments on a helical tomotherapy system. The intensity
      modulated fields are created by moving the treatment couch relative to a fan-beam
      positioned at fixed gantry angles. The delivered dose distribution is controlled
      by moving multileaf collimator (MLC) leaves into and out of the fan beam. The
      purpose of this work was to develop a leaf-sequencing algorithm for creating
      topographic MLC sequences. Topographic delivery was modeled using the analogy of
      a water faucet moving over a collection of bottles. The flow rate per unit length
      of the water from the faucet represented the photon fluence per unit length along
      the width of the fan beam, the collection of bottles represented the pixels in
      the treatment planning fluence map, and the volume of water collected in each
      bottle represented the delivered fluence. The radiation fluence per unit length
      delivered to the target at a given position is given by the convolution of the
      intensity distribution per unit length over the width of the beam and the time
      per unit distance along the direction of travel that an MLC leaf is open. The MLC
      opening times for the desired dose profiles were determined using a technique
      based on deconvolution using a genetic algorithm. The MLC opening times were
      expanded in terms of a Fourier series, and a genetic algorithm was used to find
      the best expansion coefficients for a given dose distribution. A series of wedge
      shapes (15, 30, 45, and 60 deg) and "dose well" test fluence maps were created to
      test the algorithm's ability to generate topographic leaf sequences. The accuracy
      of the leaf-sequencing algorithm was measured on a helical tomotherapy system
      using radiographic film placed at depth in water equivalent material. The
      measured dose profiles were compared with the desired dose distributions. The
      agreement was within +/- 2% or 2 mm distance-to-agreement (DTA) in the high dose
      gradient regions for all test cases. The central axis measured dose was between
      3.6% and 4.2% higher than the expected dose for the wedge cases. For the "dose
      well" test cases, the calculated and measured doses agreed to within +/- 0.5% at
      the peak and within +/- 1.6% in the "dose well." The topographic leaf-sequencing
      algorithm produced deliverable dose distributions that agreed well with the
      calculated dose distributions. This delivery technique could be used for
      treatment of whole intact breast. However, additional work is needed to further
      improve the algorithm in order to get better agreement between the calculated,
      deliverable, and measured dose distributions.

PMID- 16964851
TI  - An effective method to verify line and point spread functions measured in
      computed tomography.
AB  - This study describes an effective method for verifying line spread function (LSF)
      and point spread function (PSF) measured in computed tomography (CT). The CT
      image of an assumed object function is known to be calculable using LSF or PSF
      based on a model for the spatial resolution in a linear imaging system.
      Therefore, the validities of LSF and PSF would be confirmed by comparing the
      computed images with the images obtained by scanning phantoms corresponding to
      the object function. Differences between computed and measured images will depend
      on the accuracy of the LSF and PSF used in the calculations. First, we measured
      LSF in our scanner, and derived the two-dimensional PSF in the scan plane from
      the LSE Second, we scanned the phantom including uniform cylindrical objects
      parallel to the long axis of a patient's body (z direction). Measured images of
      such a phantom were characterized according to the spatial resolution in the scan
      plane, and did not depend on the spatial resolution in the z direction. Third,
      images were calculated by two-dimensionally convolving the true object as a
      function of space with the PSF. As a result of comparing computed images with
      measured ones, good agreement was found and was demonstrated by image
      subtraction. As a criterion for evaluating quantitatively the overall differences
      of images, we defined the normalized standard deviation (SD) in the differences
      between computed and measured images. These normalized SDs were less than 5.0%
      (ranging from 1.3% to 4.8%) for three types of image reconstruction kernels and
      for various diameters of cylindrical objects, indicating the high accuracy of PSF
      and LSF that resulted in successful measurements. Further, we also obtained
      another LSF utilizing an inappropriate manner, and calculated the images as
      above. This time, the computed images did not agree with the measured ones. The
      normalized SDs were 6.0% or more (ranging from 6.0% to 13.8%), indicating the
      inaccuracy of the PSF and LSE We could verify LSFs and PSFs for three types of
      reconstruction kernels, and demonstrated differences between modulation transfer
      functions (MTFs) derived from validated LSFs and inaccurate LSFs. Our technique
      requires a simple phantom that is suitable for clinical scanning, and does not
      require a particular phantom containing some metals or specific fine structures,
      as required in methods previously used for measurements of spatial resolution.
      Therefore, the scanned image of the phantom will be reliable and of good quality,
      and this is used directly as a confident reference image for the verification.
      When one obtains LSF, PSF or MTF values, verification using our method is
      recommended. Further, when another method for the measurement of LSF and PSF is
      developed, it could be validated using our technique, as illustrated in the
      method proposed by Boone [Med. Phys. 28, 356-360 (2001)] and used in this paper.

PMID- 16964852
TI  - Calibration procedures for seeds preloaded in cartridges.
AB  - Radioactive seeds preloaded in sterilized cartridges or needles are commonly
      obtainable from manufacturers. Under the US regulations for control of
      radioactive materials, seed users are required to account for all seeds and
      independently verify their air kerma strength (SK). As a result, the viability of
      inspection schemes that rely on measurement of aggregate seeds is of interest. In
      this paper we consider the conditions (if any) under which cartridge inspection
      can satisfy regulatory requirements and still provide practical benefit (i.e.,
      time savings) against the regular single-seed assay. The standards for comparison
      are the recommendations of AAPM TG40, AAPM TG56, and ACR's "Standard for the
      Performance of Manually Loaded Brachytherapy Sources." The practical benefit is
      judged in comparison to the effort required to apply the 10% assay recommendation
      of TG40 to seeds in cartridges. Two specific cartridge inspection schemes are
      considered: (a) measuring the SK of each cartridge in a batch; (b) measuring a
      single cartridge sampled at random from the batch. Unlike the 10% assay, which is
      defined (imperfectly, in our view) without reference to the prevalence of in
      calibration seeds, the estimation of the relative merits of cartridge inspection
      methods must necessarily include such information and, as such, is manufacturer
      specific. In this paper results are provided for Oncura model 6711 125I seeds in
      shielded and unshielded Mick cartridges. We show that the only practically useful
      cartridge inspection scheme is the batch scheme applied to unshielded cartridges.
      The false positive rates associated with the other schemes are such that we
      expect to open a cartridge (and perform the 10% assay) at least 80% of the time.
      While anything less than 100% of the time is theoretically an improvement, this
      neglects the additional effort required to assay the cartridges.

PMID- 16964853
TI  - Class solution for inversely planned permanent prostate implants to mimic an
      experienced dosimetrist.
AB  - The purpose of this paper is to present a method for the selection of inverse
      planning parameters and to establish a set of inverse planning parameters (class
      solution) for the inverse planning included in a commercial permanent prostate
      implant treatment planning system. The manual planning of more than 750 patients
      since 1996 led to the establishment of general treatment planning rules. A class
      solution is tuned to fulfill the treatment planning rules and generate equivalent
      implants. For ten patients, the inverse planning is compared with manual planning
      performed by our experienced physicist. The prostate volumes ranged from 17 to 51
      cc and are implanted with low activity 1-125 seeds. Dosimetric indices are
      calculated for comparison. The inverse planning needed about 15 s for each
      optimization (400 000 iterations on a 2.5 GHz PC). In comparison, the physicist
      needed about 20 min to perform each manual plan. A class solution is found that
      consistently produces dosimetric indices equivalent or better than the manual
      planning. Moreover, even with strict seed placement rules, the inverse planning
      can produce adequate prostate dose coverage and organ at risk protection. The
      inverse planning avoids implant with seeds outside of the prostate and too close
      to the urethra. It also avoids needles with only one seed and needles with three
      consecutive seeds. This reduces the risk of complication due to seed misplacement
      and edema. The inverse planning also uses a smaller number of needles, reducing
      the cause of trauma. The quality of the treatment plans is independent of the
      gland size and shape. A class solution is established that consistently and
      rapidly produces equivalent dosimetric indices as manual planning while
      respecting severe seed placement rules. The class solution can be used as a
      starting point for every patient, dramatically reducing the time needed to plan
      individual patient treatments. The class solution works with inverse preplanning,
      intraoperative inverse preplanning, and intraoperative real-time planning. This
      technology is not intended to replace the physicist but to accelerate the
      planning process, making intraoperative treatment planning more effective.

PMID- 16964854
TI  - Study of a prototype high quantum efficiency thick scintillation crystal video
      electronic portal imaging device.
AB  - Image quality in portal imaging suffers significantly from the loss in contrast
      and spatial resolution that results from the excessive Compton scatter associated
      with megavoltage x rays. In addition, portal image quality is further reduced due
      to the poor quantum efficiency (QE) of current electronic portal imaging devices
      (EPIDs). Commercial video-camera-based EPIDs or VEPIDs that utilize a thin
      phosphor screen in conjunction with a metal buildup plate to convert the incident
      x rays to light suffer from reduced light production due to low QE (<2% for
      Eastman Kodak Lanex Fast-B). Flat-panel EPIDs that utilize the same luminescent
      screen along with an a-Si:H photodiode array provide improved image quality
      compared to VEPIDs, but they are expensive and can be susceptible to radiation
      damage to the peripheral electronics. In this article, we present a prototype
      VEPID system for high quality portal imaging at sub-monitor-unit (subMU)
      exposures based on a thick scintillation crystal (TSC) that acts as a high QE
      luminescent screen. The prototype TSC system utilizes a 12 mm thick transparent
      CsI(Tl) (thallium-activated cesium iodide) scintillator for QE=0.24, resulting in
      significantly higher light production compared to commercial phosphor screens.
      The 25 X 25 cm2 CsI(Tl) screen is coupled to a high spatial and contrast
      resolution Video-Optics plumbicon-tube camera system (1240 X 1024 pixels, 250
      microm pixel width at isocenter, 12-bit ADC). As a proof-of-principle prototype,
      the TSC system with user-controlled camera target integration was adapted for use
      in an existing clinical gantry (Siemens BEAMVIEW(PLUS)) with the capability for
      online intratreatment fluoroscopy. Measurements of modulation transfer function
      (MTF) were conducted to characterize the TSC spatial resolution. The measured MTF
      along with measurements of the TSC noise power spectrum (NPS) were used to
      determine the system detective quantum efficiency (DQE). A theoretical expression
      of DQE(0) was developed to be used as a predictive model to propose improvements
      in the optics associated with the light detection. The prototype TSC provides
      DQE(0)=0.02 with its current imaging geometry, which is an order of magnitude
      greater than that for commercial VEPID systems and comparable to flat-panel
      imaging systems. Following optimization in the imaging geometry and the use of a
      high-end, cooled charge-coupled-device (CCD) camera system, the performance of
      the TSC is expected to improve even further. Based on our theoretical model, the
      expected DQE(0)=0.12 for the TSC system with the proposed improvements, which
      exceeds the performance of current flat-panel EPIDs. The prototype TSC provides
      high quality imaging even at subMU exposures (typical imaging dose is 0.2 MU per
      image), which offers the potential for daily patient localization imaging without
      increasing the weekly dose to the patient. Currently, the TSC is capable of
      limited frame-rate fluoroscopy for intratreatment visualization of patient motion
      at approximately 3 frames/second, since the achievable frame rate is
      significantly reduced by the limitations of the camera-control processor. With
      optimized processor control, the TSC is expected to be capable of intratreatment
      imaging exceeding 10 frames/second to monitor patient motion.

PMID- 16964855
TI  - CEnPiT: helical cardiac CT reconstruction.
AB  - Computer tomography (CT) scanners with an increasing number of detector rows
      offer the potential of shorter scanning times. Nevertheless, the reconstruction
      problem becomes more challenging, since cone beam artifacts are likely to enter.
      Here, we consider helical cardiac CT. We analyze how a relationship can be
      established between exact reconstruction algorithms and the demand to perform a
      cardiac gating. Utilizing the redundancies requires the consideration of all
      kinds of Radon planes. For the reconstruction algorithm proposed here, we
      separate the data into two parts. The first part contains contributions of Radon
      planes, which are measured with a large number of redundancies. The second part
      contains the remaining contributions. As it turns out, the second part
      contributes rather to the low-frequency contents of trans-axial slices.
      Therefore, we propose to perform a gated back-projection only for the first part,
      while the second part is back-projected in an ungated way. Data from the complete
      source trajectory are employed in the reconstruction process in contrary to
      conventional helical cardiac reconstruction methods. Moreover, all different
      types of Radon planes are taken into account in the reconstruction, though an ECG
      dependent cardiac gating is applied. The reconstruction results, which we present
      for clinical and simulated data, demonstrate the high potential of CEnPiT for
      helical cardiac CT with large cone angle systems.

PMID- 16964856
TI  - Automatic estimation of detector radial position for contoured SPECT acquisition
      using CT images on a SPECT/CT system.
AB  - An algorithm was developed to estimate noncircular orbit (NCO) single-photon
      emission computed tomography (SPECT) detector radius on a SPECT/CT imaging system
      using the CT images, for incorporation into collimator resolution modeling for
      iterative SPECT reconstruction. Simulated male abdominal (arms up), male head and
      neck (arms down) and female chest (arms down) anthropomorphic phantom, and ten
      patient, medium-energy SPECT/CT scans were acquired on a hybrid imaging system.
      The algorithm simulated inward SPECT detector radial motion and object contour
      detection at each projection angle, employing the calculated average CT image and
      a fixed Hounsfield unit (HU) threshold. Calculated radii were compared to the
      observed true radii, and optimal CT threshold values, corresponding to patient
      bed and clothing surfaces, were found to be between -970 and -950 HU. The
      algorithm was constrained by the 45 cm CT field-of-view (FOV), which limited the
      detected radii to < or = 22.5 cm and led to occasional radius underestimation in
      the case of object truncation by CT. Two methods incorporating the algorithm were
      implemented: physical model (PM) and best fit (BF). The PM method computed an
      offset that produced maximum overlap of calculated and true radii for the phantom
      scans, and applied that offset as a calculated-to-true radius transformation. For
      the BF method, the calculated-to-true radius transformation was based upon a
      linear regression between calculated and true radii. For the PM method, a fixed
      offset of +2.75 cm provided maximum calculated-to-true radius overlap for the
      phantom study, which accounted for the camera system's object contour detect
      sensor surface-to-detector face distance. For the BF method, a linear regression
      of true versus calculated radius from a reference patient scan was used as a
      calculated-to-true radius transform. Both methods were applied to ten patient
      scans. For -970 and -950 HU thresholds, the combined overall average root-mean
      square (rms) error in radial position for eight patient scans without truncation
      were 3.37 cm (12.9%) for PM and 1.99 cm (8.6%) for BF, indicating BF is superior
      to PM in the absence of truncation. For two patient scans with truncation, the
      rms error was 3.24 cm (12.2%) for PM and 4.10 cm (18.2%) for BF. The slightly
      better performance of PM in the case of truncation is anomalous, due to FOV edge
      truncation artifacts in the CT reconstruction, and thus is suspect. The
      calculated NCO contour for a patient SPECT/CT scan was used with an iterative
      reconstruction algorithm that incorporated compensation for system resolution.
      The resulting image was qualitatively superior to the image obtained by
      reconstructing the data using the fixed radius stored by the scanner. The result
      was also superior to the image reconstructed using the iterative algorithm
      provided with the system, which does not incorporate resolution modeling. These
      results suggest that, under conditions of no or only mild lateral truncation of
      the CT scan, the algorithm is capable of providing radius estimates suitable for
      iterative SPECT reconstruction collimator geometric resolution modeling.

PMID- 16964857
TI  - The susceptibility of IMRT dose distributions to intrafraction organ motion: an
      investigation into smoothing filters derived from four dimensional computed
      tomography data.
AB  - This study investigated the sensitivity of static planning of intensity-modulated
      beams (IMBs) to intrafraction deformable organ motion and assessed whether
      smoothing of the IMBs at the treatment-planning stage can reduce this
      sensitivity. The study was performed with a 4D computed tomography (CT) data set
      for an IMRT treatment of a patient with liver cancer. Fluence profiles obtained
      from inverse-planning calculations on a standard reference CT scan were
      redelivered on a CT scan from the 4D data set at a different part of the
      breathing cycle. The use of a nonrigid registration model on the 4D data set
      additionally enabled detailed analysis of the overall intrafraction motion
      effects on the IMRT delivery during free breathing. Smoothing filters were then
      applied to the beam profiles within the optimization process to investigate
      whether this could reduce the sensitivity of IMBs to intrafraction organ motion.
      In addition, optimal fluence profiles from calculations on each individual phase
      of the breathing cycle were averaged to mimic the convolution of a static dose
      distribution with a motion probability kernel and assess its usefulness. Results
      from nonrigid registrations of the CT scan data showed a maximum liver motion of
      7 mm in superior-inferior direction for this patient. Dose-volume histogram (DVH)
      comparison indicated a systematic shift when planning treatment on a motion
      frozen, standard CT scan but delivering over a full breathing cycle. The ratio of
      the dose to 50% of the normal liver to 50% of the planning target volume (PTV)
      changed up to 28% between different phases. Smoothing beam profiles with a median
      window filter did not overcome the substantial shift in dose due to a difference
      in breathing phase between planning and delivery of treatment. Averaging of
      optimal beam profiles at different phases of the breathing cycle mainly resulted
      in an increase in dose to the organs at risk (OAR) and did not seem beneficial to
      compensate for organ motion compared with using a large margin. Additionally, the
      results emphasized the need for 4D CT scans when aiming to reduce the internal
      margin (IM). Using only a single planning scan introduces a systematic shift in
      the dose distribution during delivery. Smoothing beam profiles either based on a
      single scan or over the different breathing phases was not beneficial for
      reducing this shift.

PMID- 16964858
TI  - Octree indexing of DICOM images for voxel number reduction and improvement of
      Monte Carlo simulation computing efficiency.
AB  - The purpose of the present study is to introduce a compression algorithm for the
      CT (computed tomography) data used in Monte Carlo simulations. Performing
      simulations on the CT data implies large computational costs as well as large
      memory requirements since the number of voxels in such data reaches typically
      into hundreds of millions voxels. CT data, however, contain homogeneous regions
      which could be regrouped to form larger voxels without affecting the simulation's
      accuracy. Based on this property we propose a compression algorithm based on
      octrees: in homogeneous regions the algorithm replaces groups of voxels with a
      smaller number of larger voxels. This reduces the number of voxels while keeping
      the critical high-density gradient area. Results obtained using the present
      algorithm on both phantom and clinical data show that compression rates up to 75%
      are possible without losing the dosimetric accuracy of the simulation.

PMID- 16964859
TI  - The impact of image information on compressibility and degradation in medical
      image compression.
AB  - The aim of the study was to demonstrate and critically discuss the influence of
      image information on compressibility and image degradation. The influence of
      image information on image compression was demonstrated on the axial computed
      tomography images of a head. The standard Joint Photographic Expert Group (JPEG)
      and JPEG 2000 compression methods were used in compression ratio (CR) and in
      quality factor (QF) compression modes. Image information was estimated by
      calculating image entropy, while the effects of image compression were evaluated
      quantitatively, by file size reduction and by local and global mean square error
      (MSE), and qualitatively, by visual perception of distortion in high and low
      contrast test patterns. In QF compression mode, a strong correlation between
      image entropy and file size was found for JPEG (r=0.87, p < 0.001) and JPEG 2000
      (r=0.84, p < 0.001), while corresponding local MSE was constant (4.54) or nearly
      constant (2.36-2.37), respectively. For JPEG 2000 CR compression mode, CR was
      nearly constant (1:25), while local MSE varied considerably (2.26 and 10.09). The
      obtained qualitative and quantitative results clearly demonstrate that image
      degradation highly depends on image information, which indicates that the degree
      of image degradation cannot be guaranteed in CR but only in QF compression mode.
      CR is therefore not a measure of choice for expressing the degree of image
      degradation in medical image compression. Moreover, even when using QF
      compression modes, objective evaluation, and comparison of the compression
      methods within and between studies is often not possible due to the lack of
      standardization of compression quality scales.

PMID- 16964860
TI  - GLAaS: an absolute dose calibration algorithm for an amorphous silicon portal
      imager. Applications to IMRT verifications.
AB  - A new calibration algorithm (GLAaS) to derive absolute dose maps from images
      acquired with the Varian PV-aS500 electronic portal imager (based on amorphous
      silicon detectors) has been developed incorporating the dependence of detector
      response on primary and transmitted radiation and on field size. Detector
      calibration and algorithm validation were performed at different depths (10.0,
      3.8, 1.5, and 0.8 cm) in solid water to investigate various application
      possibilities. Calibration data were obtained against ion chamber measurements.
      Validation experiments were performed on intensity-modulated fields and
      comparison was carried out against calculated dose maps as well as against film
      measurements. Split fields were acquired independently and PV-aS500 images were
      summed offline with the new algorithm allowing complex fields to be verified in
      conditions most closely resembling clinical conditions. Excellent results were
      obtained for the 3.8, 1.5, and 0.8 depths on a set of 34 modulated fields
      including both split and nonsplit fields. Applying the gamma index analysis (with
      distance to agreement and dose thresholds set to 3 mm and 4%, respectively), only
      2.3% of the field area showed gamma > 1 at 1.5 cm depth (8.1%, 3.1%, 2.7% at
      10.0, 3.8, and 0.8 and 2.5% with films at 10 cm depth). Tests were also performed
      to verify GLAaS at gantry angles different from 0 degrees. No statistical
      differences were obtained for the comparison between split and nonsplit fields
      and between different gantry angles. Highly significant statistical differences
      were obtained when comparing independent samples of 240 fields verified either
      with GLAaS or with film. Fields verified with GLAaS presented a mean area with
      gamma > 1 of 2.1 +/-1.3% while for film this value was 3.9 +/- 3.4% (p<0.001).
      Absolute dosimetry proved to be reliable with the PV-aS500 detector with the
      GLAaS algorithm. The minimal settings at depths of 1.5 or 3.8 cm would allow the
      use of the detector at any gantry angle without the need for any special fixation
      tool.

PMID- 16964861
TI  - Metal artifact reduction in CT using tissue-class modeling and adaptive
      prefiltering.
AB  - High-density objects such as metal prostheses, surgical clips, or dental fillings
      generate streak-like artifacts in computed tomography images. We present a novel
      method for metal artifact reduction by in-painting missing information into the
      corrupted sinogram. The information is provided by a tissue-class model extracted
      from the distorted image. To this end the image is first adaptively filtered to
      reduce the noise content and to smooth out streak artifacts. Consecutively, the
      image is segmented into different material classes using a clustering algorithm.
      The corrupted and missing information in the original sinogram is completed using
      the forward projected information from the tissue-class model. The performance of
      the correction method is assessed on phantom images. Clinical images featuring a
      broad spectrum of metal artifacts are studied. Phantom and clinical studies show
      that metal artifacts, such as streaks, are significantly reduced and shadows in
      the image are eliminated. Furthermore, the novel approach improves detectability
      of organ contours. This can be of great relevance, for instance, in radiation
      therapy planning, where images affected by metal artifacts may lead to suboptimal
      treatment plans.

PMID- 16964862
TI  - Verification of the agreement of two dosimetric methods with radioiodine therapy
      in hyperthyroid patients.
AB  - The aim of this study was to verify the capability of an MIRD formula-based
      dosimetric method to predict radioiodine kinetics (fraction of administered
      iodine transferred to the thyroid, U0, and effective clearance rate, lambda(eff))
      and absorbed dose after oral therapeutic 131I administration. The method is based
      on 123I intravenous administration and five subsequent gamma camera measured
      uptake values determined separately on different structures within the thyroid.
      Another dosimetric method based on only the 123I 24-h uptake and a fixed
      lambda(eff) value was also considered. Eighty-nine hyperthyroid patients (10 with
      Graves' disease and 79 with autonomously functioning nodules) were studied and
      132 thyroidal structures were evaluated. The mean time interval between dosimetry
      and therapy was 20 +/- 10d. Uptake values were measured at 2, 4, 24, 48, and 120
      h during dosimetry and at 2, 4, 24, 48, 96, and 168 h during therapy. The value
      0.125d(-1) was chosen in the fixed-lambda(eff) method. The planned doses to the
      target ranged from 120 to 250 Gy depending on the type and severity of
      hyperthyroidism. The following significant correlations between therapeutic and
      dosimetric parameters were found: U0(ther)=0.88U0(dos) (r=0.97,p<0.01),
      lambda(eff)ther = 1.01 lambda(eff)dos (r=0.85,p<0.01), and D(estimated)=
      0.85D(planned) (r=0.88, p<0.01). The percent difference between U0(ther) and
      U0(dos) ranged from -44 to 32% and between lambda(eff)ther and lambda(eff)dos
      from -32 to 48%. U0(ther) was lower than U0(dos) in 74% of cases: this can be
      explained by the self-stunning effect of 131I therapeutic activity that produced
      a dose of about 20 Gy with a maximum dose rate of 0.6 Gy/h over the initial 24-48
      h. The differences, deltaD, between the estimated and the planned doses ranged
      from -42% (-87 Gy) to 32% (59 Gy); in 73% of cases the difference was within +/-
      35 Gy. Greater discrepancies were found with the fixed-lambda(eff) method, in
      which deltaD ranged from -69 to 95% (-202 to 88 Gy, respectively). In
      hyperthyroid patients, the five uptake value dosimetric method is able to predict
      with a good agreement the radioiodine kinetics and the dose after the therapeutic
      administration in about 73% of the analyzed thyroid structures. The fixed
      lambda(eff) method is less reliable.

PMID- 16964863
TI  - Development and application of a real-time monitoring and feedback system for
      deep inspiration breath hold based on external marker tracking.
AB  - Respiration can cause tumor movements in thoracic regions of up to 3 cm. To
      minimize motion effects several approaches, such as gating and deep inspiration
      breath hold (DIBH), are still under development. The goal of our study was to
      develop and evaluate a noninvasive system for gated DIBH (GDIBH) based on
      external markers. DIBH monitoring was based on an infrared tracking system and an
      in-house-developed software. The in-house software provided the breathing curve
      in real time and was used as on-line information for a prototype of a feedback
      device. Reproducibility and stability of the breath holds were evaluated without
      and with feedback. Thirty-five patients undergoing stereotactic body radiotherapy
      (SBRT) performed DIBH maneuvers after each treatment. For 16 patients dynamic
      imaging sequences on a multislice CT were used to determine the correlation
      between tumor and external markers. The relative reproducibility of DIBH
      maneuvers was improved with the feedback device (74.5% +/- 17.1% without versus
      93.0% +/- 4.4% with feedback). The correlation between tumor and marker was good
      (Pearson correlation coefficient 0.83 +/- 0.17). The regression slopes showed
      great intersubject variability but on average the internal margin in a DIBH
      treatment situation could be theoretically reduced by 3 mm with the feedback
      device. DIBH monitoring could be realized in a noninvasive manner through
      external marker tracking. We conclude that reduction of internal margins can be
      achieved with a feedback system but should be performed with great care due to
      the individual behavior of target motion.

PMID- 16964864
TI  - Automatic identification and classification of characteristic kinetic curves of
      breast lesions on DCE-MRI.
AB  - Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the breast is
      being used increasingly in the detection and diagnosis of breast cancer as a
      complementary modality to mammography and sonography. Although the potential
      diagnostic value of kinetic curves in DCE-MRI is established, the method for
      generating kinetic curves is not standardized. The inherent reason that curve
      identification is needed is that the uptake of contrast agent in a breast lesion
      is often heterogeneous, especially in malignant lesions. It is accepted that
      manual region of interest selection in 4D breast magnetic resonance (MR) images
      to generate the kinetic curve is a time-consuming process and suffers from
      significant inter- and intraobserver variability. We investigated and developed a
      fuzzy c-means (FCM) clustering-based technique for automatically identifying
      characteristic kinetic curves from breast lesions in DCE-MRI of the breast.
      Dynamic contrast-enhanced MR images were obtained using a T1-weighted 3D spoiled
      gradient echo sequence with Gd-DTPA dose of 0.2 mmol/kg and temporal resolution
      of 69 s. FCM clustering was applied to automatically partition the signal-time
      curves in a segmented 3D breast lesion into a number of classes (i.e., prototypic
      curves). The prototypic curve with the highest initial enhancement was selected
      as the representative characteristic kinetic curve (CKC) of the lesion. Four
      features were then extracted from each characteristic kinetic curve to depict the
      maximum contrast enhancement, time to peak, uptake rate, and washout rate of the
      lesion kinetics. The performance of the kinetic features in the task of
      distinguishing between benign and malignant lesions was assessed by receiver
      operating characteristic analysis. With a database of 121 breast lesions (77
      malignant and 44 benign cases), the classification performance of the FCM
      identified CKCs was found to be better than that from the curves obtained by
      averaging over the entire lesion and similar to kinetic curves generated from
      regions drawn within the lesion by a radiologist experienced in breast MRI.

PMID- 16964865
TI  - Simulation study of respiratory-induced errors in cardiac positron emission
      tomography/computed tomography.
AB  - Heart disease is a leading killer in Canada and positron emission tomography
      (PET) provides clinicians with in vivo metabolic information for diagnosing heart
      disease. Transmission data are usually acquired with 68Ge, although the advent of
      PET/CT scanners has made computed tomography (CT) an alternative option. The fast
      data acquisition of CT compared to PET may cause potential misregistration
      problems, leading to inaccurate attenuation correction (AC). Using Monte Carlo
      simulations and an anthropomorphic dynamic computer phantom, this study
      determines the magnitude and location of respiratory-induced errors in
      radioactivity uptake measured in cardiac PET/CT. A homogeneous tracer
      distribution in the heart was considered. The AC was based on (1) a time-averaged
      attenuation map, (2) CT maps from a single phase of the respiratory cycle, and
      (3) CT maps phase matched to the emission data. Circumferential profiles of the
      heart uptake were compared and differences of up to 24% were found between the
      single-phase CT-AC method and the true phantom values. Simulation results were
      supported by a PET/CT canine study which showed differences of up to 10% in the
      heart uptake in the lung-heart boundary region when comparing 68Ge- to CT-based
      AC with the CT map acquired at end inhalation.

PMID- 16964866
TI  - Inclusion of compensator-induced scatter and beam filtration in pencil beam dose
      calculations.
AB  - Compensators can be used as beam intensity modulation devices for intensity
      modulated radiation therapy applications. In contrast with multileaf collimators,
      compensators introduce scatter and beam hardening into the therapeutic x-ray
      beam. The degree of scatter and beam filtering depends on the compensator
      material and beam energy. Pencil beam dose calculation models can be used to
      derive the shape of the compensator. In this study a novel way of incorporating
      the effect of compensator-induced scatter and beam filtration is presented. The
      study was conducted using 6, 8, and 15 MV polyenergetic pencil beams (PBs). The
      compensator materials that were studied included wax, brass, copper, and lead.
      The perturbation effects of the compensators on the PB dose profiles were built
      in the PB dose profiles and tested for regular fields containing a step
      compensator and benchmarked against DOSXYZnrc Monte Carlo calculated dose
      profiles. These effects include compensator beam filtration and Compton-scattered
      photons generated in the compensator materials that influence the resulting PB
      dose profiles. These data were obtained from DOSXYZnrc simulations. A Gaussian
      function was used to model off-axis scatter and an exponential function was used
      to model beam hardening at any radius, r. Dose profiles were calculated under a
      step compensator using the method that can model beam hardening and off-axis
      scatter, as well as a conventional method where the PB profiles are not adjusted,
      but a single effective attenuation coefficient is used instead to best match the
      dose profiles. Both sets of data were compared to the DOSXYZnrc data. Depth and
      profile dose data for 10 x 10 cm2 and 20 x 20 cm2 fields indicated that at 2 cm
      depth in water the method that takes compensator scatter into account agrees more
      closely with the DOSXYZnrc data compared to the data using only an effective
      attenuation coefficient. Further, it was found that the effective attenuation
      method can only replicate the DOSXYZnrc data at 10 cm depth where it was chosen
      to do so. At shallower depths the effective attenuation method overestimates the
      dose and beyond 10 cm depth it causes an underestimation in the dose. The scatter
      and beam hardening inclusion method does not exhibit such properties. The
      exclusion of scatter can lead to dose errors of up to 4 percent with a copper
      compensator at 5 cm depth for a 10 X 10 cm2 field under a thickness of 5 cm at 6
      MV. For materials such as lead this discrepancy could be as high as 7 to 8
      percent at 6 MV. For larger fields (20 X 20 cm2) the effect of in-phantom scatter
      reduces the differences between the dose profiles calculated with the mentioned
      methods.

PMID- 16964867
TI  - Identification of simulated microcalcifications in white noise and mammographic
      backgrounds.
AB  - This work investigates human performance in discriminating between differently
      shaped simulated microcalcifications embedded in white noise or mammographic
      backgrounds. Human performance was determined through two alternative forced
      choice (2-AFC) experiments. The signals used were computer-generated simple
      shapes that were designed such that they had equal signal energy. This assured
      equal detectability. For experiments involving mammographic backgrounds, signals
      were blurred to account for the imaging system modulation transfer function
      (MTF). White noise backgrounds were computer generated; anatomic background
      patches were extracted from normal mammograms. We compared human performance
      levels as a function of signal energy in the expected difference template. In the
      discrimination task, the expected difference template is the difference between
      the two signals shown. In white noise backgrounds, human performance in the
      discrimination task was degraded compared to the detection task. In mammographic
      backgrounds, human performance in the discrimination task exceeded that of the
      detection task. This indicates that human observers do not follow the optimum
      decision strategy of correlating the expected signal template with the image.
      Human observer performance was qualitatively reproduced by non-prewhitening with
      eye filter (NPWE) model observer calculations, in which spatial uncertainty was
      explicitly included by shifting the locations of the expected difference
      templates. The results indicate that human strategy in the discrimination task
      may be to match individual signal templates with the image individually, rather
      than to perform template matching between the expected difference template and
      the image.

PMID- 16964868
TI  - Measurement of high energy x-ray beam penumbra with Gafchromic EBT radiochromic
      film.
AB  - High energy x-ray beam penumbra are measured using Gafchromic EBT film.
      Gafchromic EBT, due to its limited energy dependence and high spatial resolution
      provide a high level of accuracy for dose assessment in penumbral regions. The
      spatial resolution of film detector systems is normally limited by the scanning
      resolution of the densitometer. Penumbral widths (80%/20%) measured at Dmax were
      found to be 2.8, 3.0, 3.2, and 3.4 mm (+/- 0.2 mm) using 5, 10, 20, and 30 cm
      square field sizes, respectively, for a 6 MV linear accelerator produced x-ray
      beam. This is compared to 3.2 mm +/- 0.2 mm (Kodak EDR2) and 3.6 mm +/- 0.2 mm
      (Kodak X-Omat V) at 10 cm x 10 cm measured using radiographic film. Using a zero
      volume extrapolation technique for ionization chamber measurements, the 10 cm X
      10 cm field penumbra at Dmax was measured to be 3.1 mm, a close match to
      Gafchromic EBT results. Penumbral measurements can also be made at other depths,
      including the surface, as the film does not suffer significantly from dosimetric
      variations caused by changing x-ray energy spectra. Gafchromic EBT film provides
      an adequate measure of penumbral dose for high energy x-ray beams.

PMID- 16964869
TI  - Vivo motion and force measurement of surgical needle intervention during prostate
      brachytherapy.
AB  - In this paper, we present needle insertion forces and motion trajectories
      measured during actual brachytherapy needle insertion while implanting
      radioactive seeds in the prostate glands of 20 different patients. The needle
      motion was captured using ultrasound images and a 6 degree-of-freedom
      electromagnetic-based position sensor. Needle velocity was computed from the
      position information and the corresponding time stamps. From in vivo data we
      found the maximum needle insertion forces to be about 15.6 and 8.9 N for 17 gauge
      (1.47 mm) and 18 gauge (1.27 mm) needles, respectively. Part of this difference
      in insertion forces is due to the needle size difference (17G and 18G) and the
      other part is due to the difference in tissue properties that are specific to the
      individual patient. Some transverse forces were observed, which are attributed to
      several factors such as tissue heterogeneity, organ movement, human factors in
      surgery, and the interaction between the template and the needle. However, theses
      insertion forces are significantly responsible for needle deviation from the
      desired trajectory and target movement. Therefore, a proper selection of needle
      and modulated velocity (translational and rotational) may reduce the tissue
      deformation and target movement by reducing insertion forces and thereby improve
      the seed delivery accuracy. The knowledge gleaned from this study promises to be
      useful for not only designing mechanical/robotic systems but also developing a
      predictive deformation model of the prostate and real-time adaptive controlling
      of the needle.

PMID- 16964870
TI  - Measurement of energy dependence for XRCT radiochromic film.
AB  - Gafchromic XRCT, radiochromic film is assessed over a broad energy range, from
      kilovoltage to megavoltage x rays for variations in reflected optical density to
      dose response. A large energy dependence was found with reflected optical density
      output for the same delivered dose varying from 7.8 +/- 0.35 at 25.5 keV (50 kVp)
      peaking at 12.1 +/- 0.5 at 54 keV (125 kVp) to 0.975 +/- 0.03 at 2300 keV (10 MV)
      when normalized to 1 at 1400 keV (6 MV) energy. The response is constant (within
      3%) in the 36-69 keV equivalent photon energy range, which corresponds to x-ray
      tube generating potentials of approximately 100-150 kVp. This matches well with
      beam qualities for diagnostic computed topography applications.

PMID- 16964872
TI  - A sensitivity-guided algorithm for automated determination of IMRT objective
      function parameters.
AB  - Optimizing intensity-modulated radiotherapy (IMRT) plans involves tradeoffs that
      balance normal-tissue objectives against each other and against tumor objectives.
      Adjusting the parameters that determine the appropriate contributions of
      individual anatomic structures to the objective functions through trial and error
      is time consuming and may not produce the best achievable plans. We have
      developed a sensitivity-guided parameter optimization (SGPO) method to assist in
      the automatic determination of parameters to drive the IMRT optimization to
      better achieve, or even exceed, specified planning goals. The method is based on
      the trade-off relationships among multiple objectives: In a globally optimal plan
      (or within a convex subspace of the plan objectives), any attempt to improve the
      achievement of goals for a structure will result in sacrificing the goals for at
      least one other structure. However, different objectives may have different
      sensitivities to the overall goal of an IMRT plan. For instance, changes in dose
      distribution, hence the subscore corresponding to an objective for a given normal
      structure, may minimally impact the target dose distribution. Stated differently,
      the target coverage is insensitive to the changes in dose distribution of the
      specific normal structure. A lung cancer treatment plan designed with the SGPO
      method was used to demonstrate that IMRT plans could be designed to favor a
      structure with the highest target sensitivity and spare the structures with the
      least target sensitivity without compromising the target coverage. Using one case
      each of prostate and paranasal sinus cancers, we also demonstrated that several
      alternative optimal solutions could be designed with the SGPO algorithm favoring
      different structures. Finally, we applied the method to eight oropharyngeal
      cancer cases to obtain objective function parameters that satisfied the Radiation
      Therapy Oncology Group RTOG-H-0022 protocol. The eight plans optimized using the
      computer-generated objective function parameters met the protocol's scoring
      criteria with no or only minor protocol violations. Our preliminary study
      indicates that the SGPO method may be an effective and practical way to improve
      IMRT planning.

PMID- 16964871
TI  - 64-element intraluminal ultrasound cylindrical phased array for transesophageal
      thermal ablation under fast MR temperature mapping: an ex vivo study.
AB  - This work was undertaken to investigate the feasibility of using a cylindrical
      phased array for transoesophaeal thermal ablation under magnetic resonance (MR)
      imaging guidance. Sixty-four transducers (0.45 mm wide by 15 mm tall), operating
      at 4.6 MHz, were spread around the periphery of a 10.6-mm-diam cylinder. The head
      of the applicator was covered with a 65-microm thick latex balloon attached using
      watertight seals. This envelope was inflated with degassed water to provide
      acoustic coupling between the transducer and the tissues. The underlying
      operating principle of this applicator is to rotate a plane ultrasound beam
      electronically. For this purpose, eight adjacent transducers were excited with
      appropriate delay times so as to generate a plane wave. The exposure direction
      was changed by exciting a different set of eight elements. Ex vivo experiments
      conducted on 47 samples of pig liver under MR temperature monitoring demonstrated
      the ability of this applicator to generate cylindrical or sector-based
      coagulation necroses at depths up to 19 mm with excellent angular precision by
      applying 20 W/cm2. MR thermometry was performed in "real-time" with segmented
      echo-planar imaging gradient echo sequences. The temporal resolution was
      approximately 3 s/ image. The average value for the temperature baseline in liver
      tissue close to the applicator was 0.3 degrees C (+/- 0.6 degrees C). The thermal
      dose delivered in tissues was computed on-line during temperature imaging.
      Excellent MR compatibility was demonstrated, all MR acquisitions were performed
      without susceptibility artifacts or radio-frequency interferences with the
      ultrasound device. Thermal lesions identified on post-treatment follow up showed
      good correlation with online MR thermometry data. The individual differences
      between measurements performed visually and using MRI thermal dose maps were
      about 11% of volume. This study demonstrated the feasibility of thermal ablation
      using a phased array intraluminal ultrasound applicator and on-line MR
      monitoring.

PMID- 16964874
TI  - Monte Carlo study of a Cyberknife stereotactic radiosurgery system.
AB  - This study investigated small-field dosimetry for a Cyberknife stereotactic
      radiosurgery system using Monte Carlo simulations. The EGSnrc/BEAMnrc Monte Carlo
      code was used to simulate the Cyberknife treatment head, and the DOSXYZnrc code
      was implemented to calculate central axis depth-dose curves, off-axis dose
      profiles, and relative output factors for various circular collimator sizes of 5
      to 60 mm. Water-to-air stopping power ratios necessary for clinical reference
      dosimetry of the Cyberknife system were also evaluated by Monte Carlo
      simulations. Additionally, a beam quality conversion factor, kQ, for the
      Cyberknife system was evaluated for cylindrical ion chambers with different wall
      material. The accuracy of the simulated beam was validated by agreement within 2%
      between the Monte Carlo calculated and measured central axis depth-dose curves
      and off-axis dose profiles. The calculated output factors were compared with
      those measured by a diode detector and an ion chamber in water. The diode output
      factors agreed within 1% with the calculated values down to a 10 mm collimator.
      The output factors with the ion chamber decreased rapidly for collimators below
      20 mm. These results were confirmed by the comparison to those from Monte Carlo
      methods with voxel sizes and materials corresponding to both detectors. It was
      demonstrated that the discrepancy in the 5 and 7.5 mm collimators for the diode
      detector is due to the water non-equivalence of the silicon material, and the
      dose fall-off for the ion chamber is due to its large active volume against
      collimators below 20 mm. The calculated stopping power ratios of the 60 mm
      collimator from the Cyberknife system (without a flattening filter) agreed within
      0.2% with those of a 10 X 10 cm2 field from a conventional linear accelerator
      with a heavy flattening filter and the incident electron energy, 6 MeV. The
      difference in the stopping power ratios between 5 and 60 mm collimators was
      within 0.5% at a 10 cm depth in water. Furthermore, kQ values for the Cyberknife
      system were in agreement within 0.3% with those of the conventional 6 MV-linear
      accelerator for the cylindrical ion chambers with different wall material.

PMID- 16964873
TI  - Optimized approach to decision fusion of heterogeneous data for breast cancer
      diagnosis.
AB  - As more diagnostic testing options become available to physicians, it becomes
      more difficult to combine various types of medical information together in order
      to optimize the overall diagnosis. To improve diagnostic performance, here we
      introduce an approach to optimize a decision-fusion technique to combine
      heterogeneous information, such as from different modalities, feature categories,
      or institutions. For classifier comparison we used two performance metrics: The
      receiving operator characteristic (ROC) area under the curve [area under the ROC
      curve (AUC)] and the normalized partial area under the curve (pAUC). This study
      used four classifiers: Linear discriminant analysis (LDA), artificial neural
      network (ANN), and two variants of our decision-fusion technique, AUC-optimized
      (DF-A) and pAUC-optimized (DF-P) decision fusion. We applied each of these
      classifiers with 100-fold cross-validation to two heterogeneous breast cancer
      data sets: One of mass lesion features and a much more challenging one of
      microcalcification lesion features. For the calcification data set, DF-A
      outperformed the other classifiers in terms of AUC (p < 0.02) and achieved
      AUC=0.85 +/- 0.01. The DF-P surpassed the other classifiers in terms of pAUC (p <
      0.01) and reached pAUC=0.38 +/- 0.02. For the mass data set, DF-A outperformed
      both the ANN and the LDA (p < 0.04) and achieved AUC=0.94 +/- 0.01. Although for
      this data set there were no statistically significant differences among the
      classifiers' pAUC values (pAUC=0.57 +/- 0.07 to 0.67 +/- 0.05, p > 0.10), the DF
      P did significantly improve specificity versus the LDA at both 98% and 100%
      sensitivity (p < 0.04). In conclusion, decision fusion directly optimized
      clinically significant performance measures, such as AUC and pAUC, and sometimes
      outperformed two well-known machine-learning techniques when applied to two
      different breast cancer data sets.

PMID- 16964875
TI  - A comparison between amplitude sorting and phase-angle sorting using external
      respiratory measurement for 4D CT.
AB  - Respiratory motion can cause significant dose delivery errors in conformal
      radiation therapy for thoracic and upper abdominal tumors. Four-dimensional
      computed tomography (4D CT) has been proposed to provide the image data necessary
      to model tumor motion and consequently reduce these errors. The purpose of this
      work was to compare 4D CT reconstruction methods using amplitude sorting and
      phase angle sorting. A 16-slice CT scanner was operated in cine mode to acquire
      25 scans consecutively at each couch position through the thorax. The patient
      underwent synchronized external respiratory measurements. The scans were sorted
      into 12 phases based, respectively, on the amplitude and direction (inhalation or
      exhalation) or on the phase angle (0-360 degrees) of the external respiratory
      signal. With the assumption that lung motion is largely proportional to the
      measured respiratory amplitude, the variation in amplitude corresponds to the
      variation in motion for each phase. A smaller variation in amplitude would
      associate with an improved reconstructed image. Air content, defined as the
      amount of air within the lungs, bronchi, and trachea in a 16-slice CT segment and
      used by our group as a surrogate for internal motion, was correlated to the
      respiratory amplitude and phase angle throughout the lungs. For the 35 patients
      who underwent quiet breathing, images (similar to those used for treatment
      planning) and animations (used to display respiratory motion) generated using
      amplitude sorting displayed fewer reconstruction artifacts than those generated
      using phase angle sorting. The variations in respiratory amplitude were
      significantly smaller (P < 0.001) with amplitude sorting than those with phase
      angle sorting. The subdivision of the breathing cycle into more (finer) phases
      improved the consistency in respiratory amplitude for amplitude sorting, but not
      for phase angle sorting. For 33 of the 35 patients, the air content showed
      significantly improved (P < 0.001) correlation with the respiratory amplitude
      than with the phase angle, suggesting a stronger relationship between internal
      motion and amplitude. Overall, amplitude sorting performed better than phase
      angle sorting for 33 of the 35 patients and equally well for two patients who
      were immobilized with a stereotactic body frame and an abdominal compression
      plate.

PMID- 16964876
TI  - Computer aided detection of clusters of microcalcifications on full field digital
      mammograms.
AB  - We are developing a computer-aided detection (CAD) system to identify
      microcalcification clusters (MCCs) automatically on full field digital mammograms
      (FFDMs). The CAD system includes six stages: preprocessing; image enhancement;
      segmentation of microcalcification candidates; false positive (FP) reduction for
      individual microcalcifications; regional clustering; and FP reduction for
      clustered microcalcifications. At the stage of FP reduction for individual
      microcalcifications, a truncated sum-of-squares error function was used to
      improve the efficiency and robustness of the training of an artificial neural
      network in our CAD system for FFDMs. At the stage of FP reduction for clustered
      microcalcifications, morphological features and features derived from the
      artificial neural network outputs were extracted from each cluster. Stepwise
      linear discriminant analysis (LDA) was used to select the features. An LDA
      classifier was then used to differentiate clustered microcalcifications from FPs.
      A data set of 96 cases with 192 images was collected at the University of
      Michigan. This data set contained 96 MCCs, of which 28 clusters were proven by
      biopsy to be malignant and 68 were proven to be benign. The data set was
      separated into two independent data sets for training and testing of the CAD
      system in a cross-validation scheme. When one data set was used to train and
      validate the convolution neural network (CNN) in our CAD system, the other data
      set was used to evaluate the detection performance. With the use of a truncated
      error metric, the training of CNN could be accelerated and the classification
      performance was improved. The CNN in combination with an LDA classifier could
      substantially reduce FPs with a small tradeoff in sensitivity. By using the free
      response receiver operating characteristic methodology, it was found that our CAD
      system can achieve a cluster-based sensitivity of 70, 80, and 90 % at 0.21, 0.61,
      and 1.49 FPs/image, respectively. For case-based performance evaluation, a
      sensitivity of 70, 80, and 90 % can be achieved at 0.07, 0.17, and 0.65
      FPs/image, respectively. We also used a data set of 216 mammograms negative for
      clustered microcalcifications to further estimate the FP rate of our CAD system.
      The corresponding FP rates were 0.15, 0.31, and 0.86 FPs/image for cluster-based
      detection when negative mammograms were used for estimation of FP rates.

PMID- 16964877
TI  - Commissioning of a conformal irradiation system for heavy-ion radiotherapy using
      a layer-stacking method.
AB  - The commissioning of conformal radiotherapy system using heavy-ion beams at the
      Heavy Ion Medical Accelerator in Chiba (HIMAC) is described in detail. The system
      at HIMAC was upgraded for a clinical trial using a new technique: large spot
      uniform scanning with conformal layer stacking. The system was developed to
      localize the irradiation dose to the target volume more effectively than with the
      old system. With the present passive irradiation method using a ridge filter, a
      scatterer, a pair of wobbler magnets, and a multileaf collimator, the width of
      the spread-out Bragg peak (SOBP) in the radiation field could not be changed.
      With dynamic control of the beam-modifying devices during irradiation, a more
      conformal radiotherapy could be achieved. In order to safely perform treatments
      with this conformal therapy, the moving devices should be watched during
      irradiation and the synchronousness among the devices should be verified. This
      system, which has to be safe for patient irradiations, was constructed and tested
      for safety and for the quality of the dose localization realized. Through these
      commissioning tests, we were successfully able to prepare the conformal technique
      using layer stacking for patients. Subsequent to commissioning the technique has
      been applied to patients in clinical trials.

PMID- 16964878
TI  - Lag and ghosting in a clinical flat-panel selenium digital mammography system.
AB  - We present measurements of lag and ghosting in a FDA-approved digital mammography
      system that uses a dielectric/selenium based detector structure. Lag is the
      carryover of signal from a previous image, whereas ghosting is the reduction of
      sensitivity caused by previous exposure history of the detector. Data from six
      selenium units were acquired. For the type of selenium detector tested, and under
      typical clinical usage conditions, the lag was as high as 0.15% of source signal
      and the ghosting could be as high as 15%. The amount of lag and ghosting varied
      from unit to unit. Results were compared with data acquired on a phosphor-based
      full-field digital mammography system. Modifications in the technology of the
      selenium detectors appear to have resulted in a marked decrease in both lag and
      ghosting effects in more recent systems.

PMID- 16964879
TI  - Accuracy of the CT numbers of simulated lung nodules imaged with multi-detector
      CT scanners.
AB  - A study was performed to determine the accuracies and reproducibilities of the CT
      numbers of simulated lung nodules imaged with multi-detector CT scanners. The
      nodules were simulated by spherical balls of three diameters (4.8, 9.5, and 16
      mm) and two compositions (50 and 100 mg/cc CaCO3 in water-equivalent plastic).
      All were scanned in a liquid-water-filled container at the center of a water
      equivalent-plastic phantom and in air cavities within the same phantom using GE
      multi-detector CT scanners. The nodules were also scanned within simulated lung
      regions in an anthropomorphic thorax section phantom that was bolused on both
      sides with water-equivalent slabs. Results were compared for three scanning
      protocols--the protocol for the National Lung Screening Trial (NLST), the
      protocol for the Lung Tissue Research Consortium (LTRC) study, and a high
      resolution (small pitch, thin slice and small scan interval) higher dose "gold
      standard" protocol. Scans were repeated three times with each protocol to assess
      reproducibility. The CT numbers of the nodules in water were found to be nearly
      independent of nodule size. However, the presence and the size of an air cavity
      surrounding a nodule had a significant effect (e.g., the CT number of a 50 mg/cc
      nodule was 64 HU in water, 37 HU in a 1.8 cm diameter air cavity, and 19 HU in a
      4.4 cm diameter air cavity). This variability of CT number with size of air
      cavity may affect the results of the LTRC study in which patients are scanned at
      both full inspiration and full expiration. The CT numbers of the 9.5 and 16 mm
      diameter nodules within the anthropomorphic phantom were highly reproducible
      (average standard deviations of 2 HU or less) for all protocols. On the other
      hand, both accuracy and reproducibility were significantly degraded for the 4.8
      mm diameter nodules, especially for the NLST (2.5 mm thickness, 2 mm slice
      interval) technique. Use of thinner slice (1.25 mm) and slice interval (1.25 mm)
      scans that can be reconstructed retrospectively from the multi-detector helical
      CT projection data of the standard NLST protocol yield CT numbers for the 4.8 mm
      diameter nodules that are more accurate and reproducible than those of the
      standard NLST technique. In general, the CT numbers of the nodules were found to
      be lower at positions near the centers of the lungs and near the spine, which is
      probably due to increased beam hardening in those regions. Also, larger nodules
      were found to have higher CT numbers than smaller nodules, consistent with
      results obtained on early single slice GE CT scanners. Until manufacturers
      develop quantitative CT scanners with improved x-ray beam hardening and scatter
      corrections, it is recommended that reference phantoms be employed to more
      accurately assess the calcium contents of patient lung nodules in screening and
      tissue characterization studies and in eventual computer-aided detection and
      diagnosis applications.

PMID- 16964880
TI  - A comparison of reconstruction algorithms for C-arm mammography tomosynthesis.
AB  - Digital tomosynthesis is an imaging technique to produce a tomographic image from
      a series of angular digital images in a manner similar to conventional focal
      plane tomography. Unlike film focal plane tomography, the acquisition of the data
      in a C-arm geometry causes the image receptor to be positioned at various angles
      to the reconstruction tomogram. The digital nature of the data allows for input
      images to be combined into the desired plane with the flexibility of generating
      tomograms of many separate planes from a single set of input data. Angular
      datasets were obtained of a low contrast detectability (LCD) phantom and cadaver
      breast utilizing a Lorad stereotactic biopsy unit with a coupled source and
      digital detector in a C-arm configuration. Datasets of 9 and 41 low-dose
      projections were collected over a 30 degrees angular range. Tomographic images
      were reconstructed using a Backprojection (BP) algorithm, an Iterative
      Subtraction (IS) algorithm that allows the partial subtraction of out-of-focus
      planes, and an Algebraic Reconstruction (AR) algorithm. These were compared with
      single view digital radiographs. The methods' effectiveness at enhancing
      visibility of an obscured LCD phantom was quantified in terms of the Signal to
      Noise Ratio (SNR), and Signal to Background Ratio (SBR), all normalized to the
      metric value for the single projection image. The methods' effectiveness at
      removing ghosting artifacts in a cadaver breast was quantified in terms of the
      Artifact Spread Function (ASF). The technology proved effective at partially
      removing out of focus structures and enhancing SNR and SBR. The normalized SNR
      was highest at 4.85 for the obscured LCD phantom, using nine projections and IS
      algorithm. The normalized SBR was highest at 23.2 for the obscured LCD phantom,
      using 41 projections and an AR algorithm. The highest normalized metric values
      occurred with the obscured phantom. This supports the assertion that the greatest
      value of tomosynthesis is in imaging fibroglandular breasts. The ASF performance
      was best with the AR technique and nine projections.

PMID- 16964881
TI  - Compatibility of interventional x-ray and magnetic resonance imaging: feasibility
      of a closed bore XMR (CBXMR) system.
AB  - A next-generation interventional guidance system is proposed that will enable
      intraprocedural access to both x-ray and magnetic resonance imaging (MRI)
      modalities. This closed bore XMR (CBXMR) system is comprised of a conventional
      radiographic rotating anode x-ray tube and a direct conversion flat panel
      detector on a rotating gantry positioned adjacent to the bore of a 1.5 T MRI. To
      assess the feasibility of such a system, we have investigated the degree of
      compatibility between the x-ray components and the MRI. For /-->B(ext)/ < 200 G
      the effect on the radiographic tube motor was negligible regardless of the
      orientation of -->B(ext) with respect to the motor axis of rotation--the
      frequency of anode rotation remained within 6% of the 3400 rpm frequency measured
      at 0 G. For /-->B(ext)/ >2400 G the anode slowed down to below 2400 rpm at all
      orientations. At intermediate B(ext), the frequency of rotation varied between
      2400 and 3200 rpm, showing a strong dependence on orientation, with -->B(ext)
      perpendicular to the tube axis having a much stronger effect on the rotation
      frequency than -->B(ext) parallel to the tube axis. In contrast to the effect of 
      ->B(ext) on the induction motor, parallel -->B(ext) had a stronger detrimental
      effect on the cathode-anode electron beam, whose path was at 16 degrees to the
      tube axis, than the perpendicular -->B(ext). Parallel -->B(ext) of several
      hundred Gauss had a defocusing effect on the x-ray focal spot. -->B(ext)
      perpendicular to the electron beam shifted the beam without significant
      defocusing. We have determined that the direct conversion flat panel detector
      (FPD) technology is not intrinsically sensitive to -->B(ext), and that the
      modifications required to make the proposed FPDs MRI compatible are minimal. The
      homogeneity of the MRI signal in the normal field of view was not significantly
      degraded by the presence of these x-ray components in the vicinity of the MRI
      bore entrance.

PMID- 16964882
TI  - Efficient photon beam dose calculations using DOSXYZnrc with BEAMnrc.
AB  - This study examines the efficiencies of doses calculated using DOSXYZnrc for 18
      MV (10 X 10 cm2 field size) and 6 MV (10 X 10 cm2 and 20 X 20 cm2 field sizes)
      photon beams simulated using BEAMnrc. Both phase-space sources and full BEAMnrc
      simulation sources are used in the DOSXYZnrc calculations. BEAMnrc simulation
      sources consist of a BEAMnrc accelerator simulation compiled as a shared library
      and run by the user code (DOSXYZnrc in this case) to generate source particles.
      Their main advantage is in eliminating the need to store intermediate phase-space
      files. In addition, the efficiency improvements due to photon splitting and
      particle recycling in the DOSXYZnrc simulation are examined. It is found that
      photon splitting increases dose calculation efficiency by a factor of up to 6.5,
      depending on beam energy, field size, voxel size, and the type of secondary
      collimation used in the BEAMnrc simulation (multileaf collimator vs photon jaws).
      The optimum efficiency with photon splitting is approximately 55% higher than
      that with particle recycling, indicating that, while most of the gain is due to
      time saved by reusing source particle data, there is significant gain due to the
      uniform distribution of interaction sites and faster DOSXYZnrc simulation time
      when photon splitting is employed. Use of optimized directional bremsstrahlung
      splitting in the BEAMnrc simulation sources increases the efficiency of photon
      beam simulations sufficiently that the peak efficiencies (i.e., with optimum
      setting of the photon splitting number) of DOSXYZnrc simulations using these
      sources are only 3-13% lower than those with phase-space file sources. This
      points towards eliminating the need for storing intermediate phase-space files.

PMID- 16964883
TI  - A practical approach for quantitative estimates of voxel-by-voxel liver perfusion
      using DCE imaging and a compartmental model.
AB  - Voxel-by-voxel estimation of liver perfusion using nonlinear least-squares fits
      of dynamic contrast enhanced computed tomography or magnetic resonance imaging
      data to a compartmental model is a computational expensive process. In this
      report, a "linear" least-squares method for estimation of liver perfusion is
      described. Simulated data and the data from an example case of a patient with
      intrahepatic cancer are presented. Compared to the nonlinear method, the new
      method can improve computational speed by a factor of approximately 400, which
      makes it practical for use in clinical trials.

PMID- 16964884
TI  - A pulse-rate dependence of dose per monitor unit and its significant effect on
      wedged-shaped fields delivered with variable dose rate and a moving jaw.
AB  - Wedge-shaped dose distributions are delivered on some modern linear accelerators
      with a virtual wedge, combining variable dose rate and a moving jaw. Drift in the
      wedge factor and wedge angle of a 20 X 20 cm field for the 60 degree virtual
      wedge was found commonplace in several models of linear accelerator from one
      manufacturer. It was found that errors in dose delivery both on and off axis
      could exceed 5% if quality assurance checks are limited to 10 X 10 cm or smaller
      fields or wedge angles of 45 degrees or less. A procedure to easily identify and
      remedy the problem is presented. In each case the change was due to variation in
      dose per monitor unit (D/MU) with the electron beam pulse rate. The variation was
      traced to a pair of circuit boards in the dosimetry system, one for each output
      measurement channel. Wedge factors and dose profiles measured before and after
      board replacement on 4 accelerators, and for a set of defective boards placed on
      one of the accelerators, were compared. The effect was largest for the wedge with
      the steepest profile (60 degree wedge angle) and the largest field measured: 20 X
      20 cm. In this case, a 1% variation in D/MU with a factor of 5 reduction in pulse
      rate corresponded to an average 0.8% change in wedge factor and 0.8% change in
      the off axis ratio at 8.5 cm off axis on the high dose side of the wedge field,
      0.3% on the low dose side. After board replacement, wedge factors and profiles
      measured on the 4 machines generally agreed to 2% for the full range of wedge
      angles and field sizes. Quality assurance of virtual wedges is discussed in light
      of the new findings.

PMID- 16964885
TI  - A completely automated CAD system for mass detection in a large mammographic
      database.
AB  - Mass localization plays a crucial role in computer-aided detection (CAD) systems
      for the classification of suspicious regions in mammograms. In this article we
      present a completely automated classification system for the detection of masses
      in digitized mammographic images. The tool system we discuss consists in three
      processing levels: (a) Image segmentation for the localization of regions of
      interest (ROIs). This step relies on an iterative dynamical threshold algorithm
      able to select iso-intensity closed contours around gray level maxima of the
      mammogram. (b) ROI characterization by means of textural features computed from
      the gray tone spatial dependence matrix (GTSDM), containing second-order spatial
      statistics information on the pixel gray level intensity. As the images under
      study were recorded in different centers and with different machine settings,
      eight GTSDM features were selected so as to be invariant under monotonic
      transformation. In this way, the images do not need to be normalized, as the
      adopted features depend on the texture only, rather than on the gray tone levels,
      too. (c) ROI classification by means of a neural network, with supervision
      provided by the radiologist's diagnosis. The CAD system was evaluated on a large
      database of 3369 mammographic images [2307 negative, 1062 pathological (or
      positive), containing at least one confirmed mass, as diagnosed by an expert
      radiologist]. To assess the performance of the system, receiver operating
      characteristic (ROC) and free-response ROC analysis were employed. The area under
      the ROC curve was found to be Az = 0.783 +/- 0.008 for the ROI-based
      classification. When evaluating the accuracy of the CAD against the radiologist
      drawn boundaries, 4.23 false positives per image are found at 80% of mass
      sensitivity.

PMID- 16964886
TI  - RHIOs: balancing capabilities and trust.

PMID- 16964887
TI  - Don't tolerate 'extortion'.

PMID- 16964888
TI  - Finance. Pension woes.

PMID- 16964889
TI  - Ambulance diversions. The ED emergency.

PMID- 16964890
TI  - Patient care. Updating an old standard.

PMID- 16964891
TI  - Quality. Time for action.

PMID- 16964892
TI  - Legal. E-disclosures.

PMID- 16964893
TI  - Data page. Changes in hospice care outpace payments.

PMID- 16964894
TI  - Save the date. Missed the Leadership Summit? Here are some highlights.
AB  - To take an organization from good to great, leaders must be willing to question
      fundamental preconceptions, be innovative and focused.

PMID- 16964895
TI  - Outpatients: here today, gone tomorrow?
AB  - Your outpatient volume is booming and that's got you feeling pretty good, right?
      Uh-oh. The fact is, most hospitals are losing outpatient market share to
      competitors like physicians' offices and nonhospital-owned facilities, and
      proposed changes to DRG payments could aggravate the situation. But some
      hospitals are finding ways to regain the upper hand.

PMID- 16964896
TI  - Emotional debriefing.
AB  - In health care, stress and sadness come with the job. Hospitals now recognize
      that letting clinicians and nonclinicians decompress--through talking groups,
      counseling or a few minutes of quiet time-is good for the soul and for the
      quality of patient care.

PMID- 16964897
TI  - Circle of Life awards 2006.
AB  - As programs to reduce pain and suffering at the end of life proliferate, this
      year's three Circle of Life winners offer useful models for other organizations.
      Two make the reduction of suffering a goal for every staff member, not just those
      on the palliative care team. The third is pioneering a model of hospice care that
      could revolutionize the field.

PMID- 16964898
TI  - Clinical communication and patient safety.
AB  - JCAHO says communication problems were the leading root cause of sentinel events
      in 2005. The reasons are manifold: a harried environment, a hierarchical staffing
      system and illegible handwriting, to name a few. This gatefold examines the scope
      of the problem, including data and risk factors, and offers some strategies for
      improvement.

PMID- 16964899
TI  - Small and rural IT challenges.

PMID- 16964900
TI  - Quality commitment. Successful programs reinforce the core elements of the IOM
      quality aims.

PMID- 16964901
TI  - Analysis of capacitance ratio of a rectangular X-cut length-extensional mode
      quartz crystal resonator by stresses.
AB  - The electrical properties of an X-cut, length-extensional mode quartz crystal
      resonator of a cut angle theta around the X-axis were calculated by a variational
      method using stresses as trial functions. Analytical expressions of stresses were
      estimated by a linear regression on a cut angle best-fit to the results of finite
      element method. The calculated dependence of the capacitance ratio on the cut
      angle was consistent with the measured results.

PMID- 16964902
TI  - Ultra-wideband SAW correlator.
AB  - A surface acoustic wave (SAW) correlator that satisfies FCC bandwidth
      requirements for ultra-wideband (UWB) operation has been built and tested. The
      correlator operates within the 3.1 to 10.6 GHz bandwidth region and uses bi-phase
      shift keying (BPSK) modulation to achieve a spreading of the main lobe to a 25%
      bandwidth. This device is capable of spreading or de-spreading a UWB signal
      directly to or from base-band to microwave frequencies.

PMID- 16964904
TI  - Propagation of thickness-twist waves in a quartz plate with asymmetric mass
      layers.
AB  - An exact solution is obtained for thickness-twist waves in a quartz plate with
      asymmetric mass layers. A simple, approximate expression for cutoff frequencies
      is given.

PMID- 16964903
TI  - On the effect of the electric field in the free space surrounding a finite
      piezoelectric body.
AB  - This note shows that a widely used approximation in analyzing motions of a finite
      piezoelectric body (i.e., the normal component of the electric displacement
      vector at an unelectroded material-air interface can be taken to be zero when the
      dielectric constant of the material is much larger than the electric permittivity
      of the free space) may lead to inaccurate results.

PMID- 16964905
TI  - An estimate on the second-order normal acceleration sensitivity of a quartz
      resonator.
AB  - An estimate is given for a second-order effect in the normal acceleration
      sensitivity of a perfectly symmetric Y-cut quartz resonator whose first-order
      normal acceleration sensitivity is zero. The order of the second-order frequency
      shift is 10-11 per g.

PMID- 16964906
TI  - Characterization of light shift below 10(-15) in a cesium fountain frequency
      standard operated without the use of mechanical shutters.
AB  - We characterize the light shift in the interaction region of a laser-cooled
      frequency standard and demonstrate an approach for its mitigation without the use
      of mechanical shutters. The light shift is confirmed to be below 10-15 and
      expected to be orders of magnitude lower. This technique makes use of a master
      slave laser configuration where cutting the injection power to a slave laser
      causes it to lase at its free-running wavelength, often two or more nanometers
      off from the atomic resonance.

PMID- 16964907
TI  - A straightforward frequency-estimation technique for GPS carrier-phase time
      transfer.
AB  - Although Global Positioning System (GPS) carrier-phase time transfer (GPSCPTT)
      offers frequency stability approaching 10-15 at averaging times of 1 d, a
      discontinuity occurs in the time-transfer estimates between the end of one
      processing batch (1-3 d in length) and the beginning of the next. The average
      frequency over a multiday analysis period often has been computed by first
      estimating and removing these discontinuities, i.e., through concatenation. We
      present a new frequency-estimation technique in which frequencies are computed
      from the individual batches then averaged to obtain the mean frequency for a
      multiday period. This allows the frequency to be computed without the uncertainty
      associated with the removal of the discontinuities and requires fewer
      computational resources. The new technique was tested by comparing the fractional
      frequency-difference values it yields to those obtained using a GPSCPTT
      concatenation method and those obtained using two-way satellite time-and
      frequency transfer (TWSTFT). The clocks studied were located in Braunschweig,
      Germany, and in Boulder, CO. The frequencies obtained from the GPSCPTT
      measurements using either method agreed with those obtained from TWSTFT at
      several parts in 1016. The frequency values obtained from the GPSCPTT data by use
      of the new method agreed with those obtained using the concatenation technique at
      1-4 x 10(-16).

PMID- 16964908
TI  - Power dependence of the frequency bias caused by spurious components in the
      microwave spectrum in atomic fountains.
AB  - The presence of spurious spectral components in the microwave excitation may
      induce frequency shifts in an atomic fountain frequency standard. We discuss how
      such shifts behave as a function of power variations of the excitation carrier
      and in the spur-to-carrier ratio. The discussion here is limited to the case of
      single-sideband spurs, which are generally much more troublesome due to their
      ability to cause frequency shifts. We find an extremely rich and unintuitive
      behavior of these frequency shifts. We also discuss how pulsed operation, typical
      of today's fountain frequency standards, relates to frequency shifts caused by
      spurs in the microwave spectrum. The conclusion of these investigations is that
      it is, at best, difficult to use elevated power microwaves in fountain frequency
      standards to test for the presence of spurs in the microwave spectrum.

PMID- 16964909
TI  - ECG triggering and gating for ultrasonic small animal imaging.
AB  - Echocardiography (ECG) is routinely used in the clinical diagnosis of cardiac
      function. The anatomy of the mouse is similar to that of the human, and thus
      murine ECG has become an effective tool for the assessment of small animal models
      of human cardiac diseases. Unfortunately, clinical ultrasonic imaging systems are
      not suitable for murine cardiac imaging due to their limited spatial and temporal
      resolutions. Murine ECG requires a spatial resolution better than 100 pim, which
      mandates the use of high-frequency, ultrasonic imaging (i.e., >20 MHz). High
      frequency transducer arrays currently are not available, and so such systems use
      the mechanical scanning of a single-element transducer for which the frame rate
      is insufficient for directly monitoring the rapid beating of a mouse heart, and
      thus retrospective image reconstruction is necessary. This paper presents a high
      frequency, ultrasonic imaging system for murine cardiac imaging. Two scanning
      methods have been developed. One is based on ECG triggering and is called the
      block scanning mode, in which the murine cardiac images from the isovolumic
      contraction and isovolumic relaxation phases are retrospectively reconstructed
      within a relatively short data acquisition time using the ECG R-wave as the
      trigger to the imaging system. The other method is the line scanning mode based
      on ECG gating, in which both ECG and ultrasound scan lines are continuously
      acquired over a longer time, enabling images during the entire cardiac cycle to
      be obtained. It is demonstrated here that the effective frame rate is determined
      by the pulse repetition frequency and can be up to 2 kHz in the presented system.

PMID- 16964910
TI  - Real-time adaptive clutter rejection filtering in color flow imaging using power
      method iterations.
AB  - We propose a new algorithm for real-time, adaptive-clutter-rejection filtering in
      ultrasound color flow imaging (CFI) and related techniques. The algorithm is
      based on regression filtering using eigenvectors of the signal correlation matrix
      as a basis for representing clutter, a method that previously has been considered
      too computationally demanding for real-time processing in general CFI
      applications. The data acquisition and processing scheme introduced allows for a
      more localized sampling of the clutter statistics and, therefore, an improved
      clutter attenuation for lower filter orders. By using the iterative power method
      technique, the dominant eigenvalues and corresponding eigenvectors of the
      correlation matrix can be estimated efficiently, rendering real-time operation
      feasible on desktop computers. A new adaptive filter order algorithm is proposed
      that successfully estimates the proper dimension of the clutter basis, previously
      one of the major drawbacks of this clutter-rejection technique. The filter
      algorithm performance and computational demands has been compared to that of
      conventional clutter filters. Examples have been included which confirms that, by
      adapting the clutter-rejection filter to estimates of the clutter-signal
      statistics, improved attenuation of the clutter signal can be achieved in normal
      as well as more excessive cases of tissue movement and acceleration.

PMID- 16964911
TI  - Characterization of digital waveforms using thermodynamic analogs: detection of
      contrast-targeted tissue in vivo.
AB  - We describe characterization of backscatter from tumor tissue targeted with a
      nanoparticle-based ultrasound contrast agent in vivo using analogs of
      thermodynamic quantities. We apply these waveform characteristics to detection of
      tumor neovasculature in tumors implanted in athymic nude mice, which were imaged
      using a research ultrasound scanner over a 2-hour period after injection of alpha
      upsilon beta3-targeted perfluorocarbon nanoparticles. Images were constructed
      from backscattered ultrasound using two different approaches: fundamental B-mode
      imaging and a signal receiver based on a thermodynamic analog (H(C)). The study
      shows that the thermodynamic analog is capable of detecting differences in
      backscattered signals that are not apparent with the B-mode approach.

PMID- 16964912
TI  - Leaky lamb waves of a piezoelectric plate subjected to conductive fluid loading:
      an experimental study.
AB  - This paper proposes a novel experimental method for measuring the propagating
      characteristics of leaky Lamb waves in a piezoelectric plate surrounded by a
      fluid. It is a differential type of measurement and is very sensitive to the
      velocity change and wave attenuation of leaky Lamb waves induced by fluid-loading
      effects. Experimental measurements on an X-cut LiNbO3 plate immersed in a
      dielectric and conductive fluid have been carried out. The velocity change and
      wave attenuation of the leaky Lamb waves caused by dielectric and conductive
      loadings of the fluid have been experimentally determined. The measured data have
      been compared with the theoretical ones that are calculated from a partial wave
      analysis. For the wave velocity, very good agreements between the experimental
      and theoretical results are observed. For the wave attenuation, there are some
      discrepancies, but an important characteristic in the relationship between wave
      attenuation and fluid conductivity as predicted by the theory have been verified
      experimentally.

PMID- 16964913
TI  - Evaluation method of TiO2-SiO2 ultra-low-expansion glasses with periodic striae
      using the LFB ultrasonic material characterization system.
AB  - Experimental procedures and standard specimens for characterizing and evaluating
      TiO2-SiO2 ultra-low expansion glasses with periodic striae using the line-focus
      beam (LFB) ultrasonic material characterization system are discussed. Two types
      of specimens were prepared, with specimen surfaces parallel and perpendicular to
      the striae plane using two different grades of glass ingots. The inhomogeneities
      of each of the specimens were evaluated at 225 MHz. It was clarified that
      parallel specimens are useful for accurately measuring velocity variations of
      leaky surface acoustic waves (LSAWs) excited on a water-loaded specimen surface
      associated with the striae. Perpendicular specimens are useful for obtaining
      periodicities in the striae for LSAW propagation perpendicular to the striae
      plane on a surface and for precisely measuring averaged velocities for LSAW
      propagation parallel to the striae plane. The standard velocity of Rayleigh-type
      LSAWs traveling parallel to the striae plane for the perpendicular specimens was
      numerically calculated using the measured velocities of longitudinal and shear
      waves and density. Consequently, a reliable standard specimen with an LSAW
      velocity of 3308.18 +/- 0.35 m/s at 23 degrees C and its temperature coefficient
      of 0.39 (m/s)/degrees C was obtained for a TiO2-SiO2 glass with a TiO2
      concentration of 7.09 wt%. A basis for the striae analysis using this ultrasonic
      method was established.

PMID- 16964914
TI  - An estimate of biofilm properties using an acoustic microscope.
AB  - Noninvasive measurements over a biofilm, a three-dimensional (3-D) community of
      microorganisms immobilized at a substratum, were made using an acoustic
      microscope operating at frequencies up to 70 MHz. The microscope scanned a 2.5-mm
      by 2.5-mm region of a living biofilm having a nominal thickness of 100 microm.
      Spatial variation of surface heterogeneity, thickness, interior structure, and
      biomass were estimated. Thickness was estimated as the product of the speed of
      sound of the medium and the interim between the highest signal peak and that of
      the substratum plane without biofilm. The thickest portions of biofilm were 145
      microm; however, slender structures attributed as streamers extended above, with
      one obtaining a 274-microm height above the substratum. Three-dimensional iso
      contours of amplitude were used to estimate the internal structure of the
      biofilm. Backscatter amplitude was examined at five zones of increasing height
      from the substratum to examine biomass distribution. Ultrasound-based estimates
      of thickness were corroborated with optical microscopy. The experimental acoustic
      and optical systems, methods used to estimate biofilm properties, and potential
      applications for the resulting data are discussed.

PMID- 16964915
TI  - Adaptive control with hysteresis estimation and compensation using RFNN for piezo
      actuator.
AB  - Because the control performance of a piezoactuator is always severely
      deteriorated due to hysteresis effect, an adaptive control with hysteresis
      estimation and compensation using recurrent fuzzy neural network (RFNN) is
      proposed in this study to improve the control performance of the piezo-actuator.
      A new hysteresis model by modifying and parameterizing the hysteresis friction
      model is proposed. Then, the overall dynamics of the piezo-actuator is completed
      by integrating the parameterized hysteresis model into a mechanical motion
      dynamics. Based on this developed dynamics, an adaptive control with hysteresis
      estimation and compensation is proposed. However, in the designed adaptive
      controller, the lumped uncertainty E is difficult to obtain in practical
      application. Therefore, a RFNN is adopted as an uncertainty observer in order to
      adapt the value of the lumped uncertainty E on line. And, some experimental
      results show that the proposed controller provides high-performance dynamic
      characteristics and is robust to the variations of system parameters and external
      load.

PMID- 16964916
TI  - Systematic design approach for capacitively coupled microelectromechanical
      filters.
AB  - A design procedure for microelectromechanical (MEMS) band-pass filters is
      formulated that takes into account specifications set for carrier-to-interference
      ratio (C/I) and insertion loss. Since suppressing intermodulation distortion to
      maximize C/I in MEMS filter design typically leads to increased loss and vice
      versa, it is necessary to aim at a feasible compromise in filter performance that
      meets all of the requirements. In order to meet specifications that are typical
      for a handheld communication terminal, an integrated receiver architecture, where
      filter input and output impedances other than 50 omega can be used, is found to
      be more feasible than resistively terminating the front-end filter at source and
      load to 50 omega.

PMID- 16964917
TI  - Study on a new type of radial composite piezoelectric ultrasonic transducers in
      radial vibration.
AB  - In this paper, a new type of radial composite ultrasonic transducers in radial
      vibration is presented and studied. The radial composite ultrasonic transducer
      consists of a solid piezoelectric ceramic thin disk and a hollow metal thin,
      circular ring in radial vibration; and they are connected together in the radial
      direction. The radial vibrations of a piezoelectric ceramic thin disk and a
      hollow, metal, thin, circular ring are analyzed, respectively. Their radial
      electromechanical equivalent circuits are obtained. Based on the
      electromechanical equivalent circuits and using the boundary conditions between
      the piezoelectric ceramic thin disk and the hollow, metal, thin ring, the
      electromechanical equivalent circuit of the radial composite ultrasonic
      transducer is derived and the resonance frequency equation is obtained. The
      theoretical results from the resonance frequency equation are in good agreement
      with the measured radial resonance frequencies, and they also are in a good
      agreement with the results from the numerical method.

PMID- 16964918
TI  - Fabrication of PZT sol gel composite ultrasonic transducers using batch
      fabrication micromolding.
AB  - A new micromolding technique for fabricating high-frequency (>20 MHz) ultrasound
      transducers has been developed. The technique combines sol gel processing with an
      epoxy-based, photo-resist Su-8 micromold to form miniature PZT structures. An
      advantage of this technique as compared to more traditional lithographic
      galvanforming and abforming (LIGA) processing is that the intermediate step of
      producing a nickel-plated mold is avoided. Instead, the PZT is formed directly
      using a photo-resist. The resulting structures can be fabricated with aspect
      ratios up to 3:1 and thicknesses up to 50 micro. We have successfully fabricated
      50-micro-thick linear array elements with 23-micro-wide elements separated by 15
      kerfs. A 50-micro thick, 2.5-mm diameter, five-element annular array structure
      with 20-micro kerfs also has been fabricated. The micromolded PZT composite has a
      density of 5.7-5.8 micro 0.4 g/cm3 and a thickness coupling coefficient as high
      as 0.32.

PMID- 16964919
TI  - To simulate blackbody radiation frequency shift in cesium fountain frequency
      standard with CO2 laser.
AB  - An experimental scheme to simulate the Blackbody radiation (BBR) frequency shift
      with carbon dioxide (CO2) laser in cesium fountain frequency standard is
      proposed. The alternative (ac) electric field from a CO2 laser with 10.6 microm
      wavelength causes the similar ac Stark shift of the clock transition frequency,
      but with much higher intensity than BBR power intensity at about room
      temperature. This scheme provides a simple, new method for measuring the BBR
      frequency shift in fountain clock. It provides the possibility to explain the
      difference of BBR shifts in Cs fountain clocks between two measurement methods.

PMID- 16964920
TI  - Statistics of the radio-frequency signal based on K distribution with application
      to echocardiography.
AB  - We study in this paper the statistics of the radio frequency (RF) signal in the
      case of partially developed speckle. Using the K distribution framework, we give
      the probability density function of the associated distribution, the
      corresponding moments, and estimators for the parameters of the distribution. The
      consistency of the proposed estimators is evaluated in terms of their bias and
      variance through numerical simulations. The ability of the proposed distribution
      to model RF echographic signals from cardiac tissues is evaluated from data
      acquired in vivo.

PMID- 16964921
TI  - Antiplane piezoelectric surface waves over a ceramic half-space with an
      imperfectly bonded layer.
AB  - We study surface wave propagation over a piezoelectric half-space with an
      imperfectly bonded mass layer. The imperfect interface between the half-space and
      the layer is described by the so-called shear-lag model with an elastic constant
      characterizing the interface physical property. An analytical solution is
      obtained. Discussion and numerical solutions are presented.

PMID- 16964922
TI  - [Interrelations between plant communities and environmental factors of wetlands
      and surrounding lands in mid- and lower reaches of Tarim River].
AB  - A total of 16 quadrants of wetlands and surrounding lands in the mid- and lower
      reaches of Tarim River were surveyed, and the data about the characteristics of
      plant communities and environmental factors were collected and counted. By using
      PCA (principal component analysis) ordination and regression procedure, the
      distribution patterns of plant communities and the relationships between the
      characteristics of plant community structure and environmental factors were
      analyzed. The results showed that the distribution of the plant communities was
      closely related to soil moisture, salt, and nutrient contents. The accumulative
      contribution rate of soil moisture and salt contents in the first principal
      component accounted for 35.70%, and that of soil nutrient content in the second
      principal component reached 25.97%. There were 4 types of habitats for the plant
      community distribution, i. e., fenny--light salt--medium nutrient, moist--medium
      salt--medium nutrient, mesophytic--medium salt--low nutrient, and medium
      xerophytic-heavy salt--low nutrient. Along these habitats, swamp vegetation,
      meadow vegetation, riparian sparse forest, halophytic desert, and salinized shrub
      were distributed. In the wetlands and surrounding lands of mid- and lower reaches
      of Tarim River, the ecological dominance of the plant communities was markedly
      and unitary-linearly correlated with the compound gradient of soil moisture and
      salt contents. The relationships between species diversity, ecological dominance,
      and compound gradient of soil moisture and salt contents were significantly
      accorded to binary-linear regression model.

PMID- 16964923
TI  - [Physiology and ecology of Pometia tomentosa photosynthesis in tropical seasonal
      rain forest].
AB  - Pometia tomentosa is a dominant uppermost canopy tree in Xishuangbanna tropical
      seasonal rain forest. In this paper, the photosynthetic characteristics of the
      three layers of P. tomentosa canopy were measured with Li-6400 portable
      photosynthesis system, and the results showed that P. tomentosa had the
      characteristics of high light saturation point (1 000 - 1 500 micromol x m(-2) x
      s(-1)) and low compensation point (7.7 - 15.3 micromol x m(-2) x s(-1)). Its leaf
      photosynthesis had the adaptive responses when the high irradiance changed. PAR
      was the main factor affecting the diurnal changes of net photosynthesis. In
      December, the leaf grew well, and had a high ability of photosynthesis, with the
      diurnal change of P. for upper layer exhibiting single-peaked pattern and the
      maximum value being 8.9 micromol CO2 x m(-2) x s(-1). April was the alternative
      period of old and young leaves, and the ability of photosynthesis was dropped,
      with the diurnal change of P(n) for upper layer following double-peaked curve and
      the maximum value being 4.3 micromol CO2 x m(-2) x s(-1). The highest net
      photosynthesis rate was observed in July, with the diurnal change of P. for upper
      and middle layers exhibiting single-peaked pattern and that for lower layers
      being double-peaked. Short-term enriched CO2 concentration could evidently
      increase the photosynthesis of P. tomentosa, while the stomatic conductance and
      transpiration would be inhibited. When the CO, concentration increased from 400
      micromol x mol(-1) to 800 micromol x mol(-1), water use efficiency (WUE) was
      increased by 50% - 100% in dry season, but rather low in wet season.

PMID- 16964924
TI  - [Soil moisture characteristics at the boundary of forestland-grassland in hilly
      area of Loess Plateau].
AB  - In this paper, the spatial distribution pattern of soil moisture at the boundary
      of forestland-grassland in hilly area of Loess Plateau was studied in dry season
      of June and rainy season of August 2004. The results showed that the variance
      coefficient of soil moisture content was smaller, and the difference of moisture
      content between soil layers was less significant in forestland than in grassland
      in June while reversed in August. There was a weak or medium differentiation of
      moisture content in different soil layers at the boundary of forestland
      grassland. The edge effect area at the boundary was from 2 m (0. 4 of tree
      height) outside forestland to 2 m inside forestland in June, and from 2 m outside
      forestland to 4 m (0. 8 of tree height) inside forestland in August. The
      forestland-grassland landscape could be divided into 3 parts, i.e., grassland
      area, forest edge area, and forestland area, and the vertical distribution of
      soil moisture in these three parts showed different traits. In June, soil
      moisture content increased with increasing soil depth, with a smaller increment
      in grassland than in forestland, but in August, it was reversed. The vertical
      distribution of soil moisture at forest edge area showed an in-between feature.

PMID- 16964925
TI  - [Physiological-ecological effects of Populus davidiana--Quercus liaotungensis
      mixed forest in Ziwuling forest area].
AB  - This paper studied the soil physical- properties under Populus davidiana, Quercus
      liaotungensis, and Populus davidiana--Quercus liaotungensis mixed forest in the
      Ziwuling forest area of Loess Plateau, and the leaf photosysthetic
      characteristics of these three types of forests. The results showed that soil
      moisture content in 0 - 300 cm layer was the highest under P. davidiana forest,
      and obviously increased below 200 cm in depth under P. davidiana--Q.
      liaotungensis mixed forest, which was 10.5% - 19.76% higher than that under Q.
      liaotungensis forest. In 0 - 60 cm layer, P. davidiana forest showed the highest
      soil bulk density and the lowest soil porosity, while P. davidiana--Q.
      liaotungensis mixed forest presented the lowest soil bulk density and the highest
      soil porosity, and both of these indices surpassed their corresponding values
      under pure forests, which indicated that the mixed forest could make effective
      use of water in deep soil, and obviously improved soil physical and chemical
      properties. P. davidiana and Q. liaotungensis had a higher content of leaf
      chlorophyll than P. davidiana--Q. liaotungensis mixed forest, and Q.
      liaotungensis presented the highest leaf chlorophyll content. Q. liaotungensis
      had the highest photosynthetic rate and stomatal conductance, followed by P.
      davidiana, and by P. davidiana--Q. liaotungensis mixed forest. The water use
      efficiency of the forests ranked in the decreasing order of Q. liaotungensis in
      pure forest, Q. liaotungensis in mixed forest, P. davidiana in mixed forest, and
      P. davidiana in pure forest. Q. liaotungensis in mixed forest presented the
      highest F(v)/F(m) and F(v)/F(o), and did not remarkably differ from those in pure
      forest, but in the mixed forest, the F(v)/F(m) and F(v)/F(o) of P. davidiana were
      markedly lower than those of P. davidiana in pure forest. Both the q(p) and NPQ
      of P. davidiana and Q. liaotungensis in pure forests were higher than those in
      mixed forest, respectively. In Ziwuling forest area, Q. liaotungensis in Q.
      liaotungensis--dominant climax community tended to be more stable, and grew
      better than Q. liaotungensis in P. davidiana--Q. liaotungensis mixed forest, and
      P. davidiana would be gradually replaced. Compared with P. davidiana in pure
      forest, P. davidiana in its mixed forest was at a disadvantage in its growth.

PMID- 16964926
TI  - [Fog water absorption by the leaves of epiphytes and non - epiphytes in
      Xishuangbanna].
AB  - Xishuangbanna is located at the northern margin of tropics. Its climate is
      different from that of typical tropics, but the rainforest there is not very
      different from that of the typical tropics in Southeast Asia. The main problems
      in Xishuangbanna are seasonal drought and low temperature. Fog may contribute to
      the development of rainforest here, but related studies are few. This study is
      aimed to know whether the leaves of epiphytes and non - epiphytes in
      Xishuangbanna can directly absorb fog water and contribute to their water status
      recovery, and whether epiphytes are more competent than non - epiphytes in their
      leaf fog water absorption. The study was conducted in dry season, and four
      species of epiphytes and six species of non - epiphytes were investigated. The
      effect of fog was imitated by spraying leaves with distilled water. For epiphytes
      and non - epiphytes, their leaf water potential (phi), relative water content
      (RWC), and amount of absorbed water increased gradually with the time of
      spraying, but the phi of epiphytes increased more quickly than that of non -
      epiphytes. The leaves of epiphytes Bolbitis scandens and Rhaphidophora decursiva
      could absorb fog water more quickly, and increase their RWC more greatly than
      those of non - epiphytes, indicating that these epiphytes were more competent
      than non - epiphytes in their leaf fog water absorption. The fog water absorption
      capacity of the leaves in epiphytic orchid Coelogyne occultata and Staurochilus
      dawsonianus was lower than that in Amischotolype hispida and Mananthus
      patentflora, but higher than that in other four non - epiphytes. The phi of
      epiphytes at early evening when no fog was formed was significantly lower than
      that at early morning, suggesting that fog water was absorbed by epiphytes at
      night to improve their leaf water status. Non - epiphytes did not need to absorb
      fog water directly through leaves, and they could recover their leaf water status
      through absorbing soil water by root system. Epiphytes except C. occultata had a
      much more leaf biomass than non - epiphytes, which was also beneficial to their
      leaf fog water absorption. Because there was abundant fog in dry season in
      Xishuangbanna, the phi of test ten species was higher than -0.8 MPa, indicating
      that water stress was not serious in dry season.

PMID- 16964927
TI  - [Seed population dynamics and germination characteristics of Eupatorium
      adenophorum].
AB  - With bare land, farmland, and masson pine forestland in the Eupatorium
      adenophorum- invaded area of Dechang County, Sichuan Province as test habitats,
      this paper studied the seed population dynamics of E. adenophorum at the levels
      of seed rain and seed bank, and its seed germination characteristics under
      effects of light and soil medium. The results showed that in the three habitats,
      the seed population of E. adenophorum only existed from March to June, and
      reached its peak by the end of April. The annual seed rainfall in bare land
      habitat amounted to 2.4 x 10(5) individuals per square meter, and all the seeds
      were distributed in the soil layer above 2 cm. The thousand seed weight and seed
      activity of E. adenophorum in bare land habitat were significantly higher than
      those in another two habitats. No active seed was found in the three habitats by
      the first ten days of July. Under artificial light condition, full light had some
      inhibitory effects on seed germination, while 28% of full light gave the highest
      germination rate. Sandy loam soil was more favorable for the seed germination,
      while in un-reclaimed red soil, both the germination velocity and germination
      rate were the lowest.

PMID- 16964928
TI  - [Competitive mechanism of non - predator - prey metapopulation system based on
      competition and dispersal ability].
AB  - Species competition is one of the important ecological courses that influence the
      evolvement of ecosystem. To an ecosystem of predator - prey, competition is
      always bidirectional, that is there is competitive infection on superior species
      and inferior species. Without regarding to the destruction of habitat, the
      bidirectional competitive mechanism was introduced, Tilman' unilateral
      competitive model was extended to bidirectional competitive model of
      metapopulation. At the same time, the competitive dynamics of the 6-
      metapopulation species are simulated on computer. The results showed that at the
      equilibrium, the coexistence condition of population competition is migratory
      ability and competition ability take on exponential negative correlation, the
      outcome of competition makes the superior and inferior sequence changed, the
      exclusion and coexistence of species competition was affected by migratory
      ability and competition ability, the metapopulations which are excluded in local
      patches can exist in regional scale, that is escaping coexistence.

PMID- 16964929
TI  - [Effects of forest and swamp on hydrochemical characteristics of streams].
AB  - With the upper reaches of Gongbiela River in the northeast part of Xiaoxing' an
      Mountains as test area, this paper studied the hydrochemical characteristics of
      the streams in forest and swamp during the period of June - September 2004. The
      results indicated that the hydrochemistry of forest and swamp streams belonged to
      calcium-bicarbonate type I (C1(Ca)). The pH value, mineralization rate, total
      hardness, and HCO3(-), SO4(2-), Ca(2+), Mg(2+) and Fe concentrations of forest
      streams were lower than those of swamp streams, while the concentrations of total
      N, total P, Cl-, K+, and Na+ were in adverse. In both of the streams, the
      contents of heavy metal elements such as Fe, Mn, Cu, Zn, Cd, Hg and Pb were lower
      than the class I in Environmental Quality Standards for Surface Water (EQSSW) of
      China. The concentrations of total N and P in forest streams were (0.27 +/- 0.04)
      mg x L(-1) and (0.040 +/- 0.005) mg x L(-1), respectively, being significantly
      higher than those ((0.21 +/- 0.02) mg x L(-1) and (0.025 +/- 0.004) mg x L(-1))
      in swamp streams. Swamp wetland had a stronger ability in depositing and
      adsorbing N and P, with more NH4(+) -N adsorbed than NO3(-) -N, and also had a
      stronger ability on the reduction and release of Fe, with the Fe content ((0.26
      +/- 0.05) mg x L(-1)) in its streams obviously higher than that in forest
      streams.

PMID- 16964930
TI  - [Hyperspectral remote sensing estimation models on vegetation coverage of natural
      grassland].
AB  - By using ASD FieldSpec Pro FR spectroradiometer, the spectral measurement of
      natural grassland in Xilingole Leaguer of Inner Mongolia was performed, with the
      vegetation coverage of natural grassland calculated, and the correlation of 25
      hyperspectral feature variables with the vegetation coverage of natural grassland
      was analyzed. The results showed that there were 17 variables correlated
      significantly with the vegetation coverage of natural grassland, among which, the
      correlation coefficient between vegetation coverage and the area of red edge peak
      calculated as the sum of the amplitudes between 680 nm and 780 nm (sigma dr 680 -
      780 nm) was the highest, with the value of 0.781. The basic experimental data
      including the vegetation coverage and canopy reflectance of natural grassland
      were classified into two groups. One group was used as the training sample to
      build the regression models with one-sample linear method, nonlinear method, and
      stepwise analysis method, while the other was used as the testing sample to test
      the precision of regression models. It was suggested that the variable of the
      area of red edge peak calculated as the sum of amplitudes between 680 nm and 780
      nm (sigma dr 680 - 780 nm) was the best one to univariate general linear model,
      with a standard deviation of 10.4% and an estimation precision of 83.99%, while
      the stepwise regression technique was not effective to estimate the grassland
      coverage with raw hyperspectral canopy reflectance.

PMID- 16964931
TI  - [Distribution of organic carbon pools in different sizes of soil aggregates in
      Loess Plateau].
AB  - According to the types of vegetation and soil, 22 soil profile samples (0 - 20
      cm, 20 - 40 cm and 40 - 60 cm) were collected from different regions of Loess
      Plateau to approach the distribution of organic carbon pools in different sizes
      of soil aggregates. The results showed that the organic carbon content and
      storage in all sizes of soil aggregates were decreased with increasing soil
      depth. For each soil layer, the organic carbon content had an increasing trend in
      the aggregates with the sizes from > 5 mm, 2 - 5 mm, 1 - 2 mm to 0.25 - 1 mm, and
      a descreasing trend from 0.25 - 1 mm to < 0. 25 mm. Because of the different
      proportions of each size of soil aggregates, the organic carbon storage and
      content in different sizes of soil aggregates were not the same, i. e., the
      storage was decreased with the sizes from > 5 mm, 2 - 5 mm to 1 - 2 mm, while
      increased from 1 - 2 mm, 0.25 - 1 mm to < 0. 25 mm. Except Eum-Orthic Anthrosols
      had the highest organic carbon content in its aggregate of < 0.25, Ust-Sandiic
      Entisols, Los-Orthic Entisols and Hap-Ustic Isohumisols had a peak value in their
      aggregate of 0.25 - 1 mm. The organic carbon storage was the highest in the
      aggregate of < 0.25 mm in Ust-Sandiic Entisols and Los-Orthic Entisols, and in
      the aggregate of > 5 mm in Hap-Ustic Isohumisols and Eum-Orthic Anthrosols. The
      soil organic carbon content and storage under different types of vegetation had
      the trend of natural forestland > bare land > artificial forest land > farming
      land.

PMID- 16964932
TI  - [Spatial analysis on land use in Xishuangbanna].
AB  - Based on remote image and GIS technology, this paper analyzed the relationships
      between land use system and natural topographic factors such as elevation, slope,
      and river system in Xishuangbanna. The results showed that the land use system in
      the study region was dominated by forestland, cropland and grassland. The area of
      forestland was 13 420 km, accounting for 74% of the total, and that of cropland
      and grassland was 3 251 km2 and 2 332 km2, accounting for 13% and 18% of the
      total, respectively. The areas of these three land use types varied with
      elevation in single-peaked curve. Forestland mainly distributed around the
      elevation of 1 000 - 1 200 m, while cropland and grassland centralized at the
      elevation of 900 m. Urban land and cropland, which were greatly influenced by
      human activity, had lower slope index than forestland and grassland. Besides
      elevation and slope, river system in valley had effects on land use condition.
      With increasing buffer distance in valley, a strong spatial pattern of land use
      type was presented, i. e. , cropland, urban land and unused land concentrated
      greatly adjacent to water, while forestland and grassland were far away from
      valley. A landscape with relatively primary status, which was comprised of
      forestland as matrix, river as corridor, and cropland as patch, would come into
      being.

PMID- 16964933
TI  - [Soil organic carbon storage and its spatial distribution characteristics in
      Hainan Island: a study based on HNSOTER].
AB  - The study based on HNSOTER and supported by GIS showed that in Hainan Island, the
      total amount of soil organic carbon in the standard profile depth of 0 - 100 cm
      was about 2.78 x 10(8) t, and the soil organic carbon density in 0 - 20 cm and 0 
      100 cm profile depth was 0.3 - 18.8 kg x m(-2) and 1.0 - 32.1 kg x m(-2), with
      an area-weighted means of 3.3 kg x m(-2) and 8.4 kg x m(-2), respectively. Soil
      organic carbon density varied significantly with different landform, lithology
      and soil, which tended to decrease from the mountains in the middle part of
      Hainan Island to its coastal plain, and had some differences between 0 - 20 cm
      and 0 - 100 cm profile depth. The areas of high soil organic carbon density in 0 
      20 cm profile depth were mainly distributed in the mountains and northern basalt
      tableland, while those in 0 - 100 cm profile depth were in the middle-eastern
      mountains and tableland. The distribution center of soil organic carbon density
      in 0 - 100 cm profile depth had a significant shift to the eastern part, compared
      with that in 0 - 20 cm profile depth.

PMID- 16964934
TI  - [Calculation of soil water erosion modulus based on RUSLE and its assessment
      under support of artificial neural network].
AB  - With Hengshan County of Shanxi Province in the North Loess Plateau as an example,
      and by using ETM + and remote sensing data and RUSLE module, this paper
      quantitatively derived the soil and water loss in loess hilly region based on
      "3S" technology, and assessed the derivation results under the support of
      artificial neural network. The results showed that the annual average erosion
      modulus of Hengshan County was 103.23 t x hm(-2), and the gross erosion loss per
      year was 4. 38 x 10(7) t. The erosion was increased from northwest to southeast,
      and varied significantly with topographic position. A slight erosion or no
      erosion happened in walled basin, flat-headed mountain ridges and sandy area,
      which always suffered from dropping erosion, while strip erosion often happened
      on the upslope of mountain ridge and mountaintop flat. Moderate rill erosion
      always occurred on the middle and down slope of mountain ridge and mountaintop
      flat, and weighty rushing erosion occurred on the steep ravine and brink. The
      RUSLE model and artificial neural network technique were feasible and could be
      propagandized for drainage areas control and preserved practice.

PMID- 16964935
TI  - [Nitrogen flow in Huizhou region].
AB  - Eutrophication is a serious problem of water body pollution. By the method of
      material flow accounting, this paper studied the human activities- related
      nitrogen flow in the system of environment and anthroposphere in Huizhou region.
      The non-point source pollution was quantified by export coefficient method, and
      the domestic discharge was estimated by demand-supply method. The statistic and
      dynamic analyses based on the investigation data of 1998 showed that the major
      nitrogen flows in this region were river loads, fertilizer and feedstuff imports,
      atmospheric deposition, animal excretes' degradation and volatilization, and the
      processes relating to burning and other emissions. In 1998, about 40% of nitrogen
      was detained in the system, which could be accumulated and yield potential
      environmental problems. The nitrogen export in this region was mainly by rivers,
      accounted for about 57%. A comparison of Huizhou region with the Danube and
      Changjiang basins showed that the unit area nitrogen exports in these three
      regions were of the same magnitude, and the per capita nitrogen exports were
      comparable.

PMID- 16964936
TI  - [Ecological environmental quality assessment of Hangzhou urban area based on RS
      and GIS].
AB  - In allusion to the shortage of traditional ecological environmental quality
      assessment, this paper studied the spatial distribution of assessing factors at a
      mid-small scale, and the conversion of integer character to girding assessing
      cells. The main assessing factors including natural environmental condition,
      environmental quality, natural landscape and urbanization pressure, which were
      classified into four types with about eleven assessing factors, were selected
      from RS images and GIS-spatial analyzing environmental quality vector graph.
      Based on GIS, a comprehensive assessment model for the ecological environmental
      quality in Hangzhou urban area was established. In comparison with observed urban
      heat island effects, the assessment results were in good agreement with the
      ecological environmental quality in the urban area of Hangzhou.

PMID- 16964937
TI  - [Effects of soil surface mulching on the growth and physiological characteristics
      of grafted and non-grafted cucumbers in solar greenhouse].
AB  - This paper studied the effects of wheat straw mulching, plastic film mulching,
      and wheat straw plus plastic film mulching on the growth and physiological
      characteristics of grafted and non-grafted Cucumis sativus in solar greenhouse.
      The results showed that compared with the control, the plant height, stem
      diameter, photosynthetic rate, and root vitality of grafted C. sativus under
      wheat straw plus plastic film mulching, plastic film mulching, and wheat straw
      mulching were increased by 91, 71 and 57 cm, 0.127, 0.086 and 0.111 cm, 2.63,
      2.08 and 1.36 micromol x m(-2) x s(-1), and 0.98, 0.48 and 0.8 mg TTC x g(-1) FW,
      respectively, while non-grafted C. sativus had a less increment. The chlorophyll
      content of grafted C. sativus under wheat straw plus plastic film mulching and
      wheat straw mulching was 1.8% and 3.15% higher than the control, respectively,
      but that under plastic film mulching was 3.8% less than the control. Soil surface
      mulching increased the dry weight per plant, early yield, and total yield. Under
      wheat straw plus plastic film mulching, plastic film mulching, and wheat straw
      mulching, the individual yield of grafted C. sativus was 16%, 5.3% and 3.4%
      higher than that of non-grafted C. sativus, respectively.

PMID- 16964938
TI  - [Antioxidant enzyme activities and proline content in maize seedling and their
      relationships to cold endurance].
AB  - This paper studied the catalase (CAT) and peroxidase (POD) activities and proline
      (Pro) content in the seedling's root, mesocotyl (including coleoptile node) , and
      coleoptile (including infancy leaf) of two maize inbred lines Huang C (cold
      endurance) and Mo17 (cold-sensitive), and their relationships to cold endurance
      under low temperature stress (5 degrees C, 3 d). The results showed that under
      the low temperature stress, Huang C had a significantly higher relative growth
      rate of mesocotyl and coleoptile than Mo17, and the change rates of CAT and POD
      activities and Pro content in the root, mesocotyl and coleoptile of Huang C were
      higher than those of Mo17. The plasma membrane permeability of the three segments
      of both inbred lines was significantly increased, but Huang C had significantly
      lower plasma membrane permeability than Mo17. Compared with those under normal
      temperature, the seedlings under low temperature stress had higher CAT activity
      and Pro content, and the increment was higher in Huang C than in Mo17. The POD
      activity in the three segments of the seedlings under low temperature stress was
      reduced, and the decrement was lower in Huang C than in Mo17. Stepwise regression
      analysis showed that under low temperature stress, the dry matter accumulation in
      cold-endurance line Huang C was mainly related to Pro content, while that in cold
      sensitive line Mo17 was mainly related to POD activity. Mesocotyl was the most
      responsive tissue to low temperature. The change rate of Pro content in mesocotyl
      was more closely correlated with the cold endurance of maize inbred lines than
      the other physiological parameters.

PMID- 16964939
TI  - [Physiological and biochemical indexes of drought resistance of sugarcane
      (Saccharum spp.)].
AB  - Through factor analysis and grey correlative degree analysis, this paper studied
      the relationships of sugarcane leaf relative water content (RWC), membrane lipid
      peroxidation metabolism, active oxygen metabolism, photosynthesis, and stalk
      yield with drought resistance of sugarcane. The results suggested that under
      drought stress, the plasma membrane permeability (PMP) and malondialdehyde (MDA)
      content were markedly increased, while RWC, superoxide dismutase (SOD) activity,
      chlorophyll (Chl) content, PS II photochemical efficiency (F(v)/ F(m)), PS II
      potential activity (F(v)/F(o)), variable fluorescence quenching rate
      (deltaF(v)/F(o)), efficiency of potential quantum conversion (deltaF(v)/F(t)),
      and single stalk weight (SSW) were remarkably decreased. The correlation of SSW
      with test indexes was decreased in the order of PMP, SOD activity, MDA content,
      RWC, F(v)/F(o), F(v)/F(m), Chl content, deltaF(v)/F(o) and deltaF(v)/F(t).
      Through factor analysis, the test indexes were divided into four common factors,
      among which, the indexes of photosynthesis played important roles in the first
      factor, RWC and the indexes of active oxygen metabolism dominated in the second
      factor, while SSW and Chl content played primary roles in the third and fourth
      factor, respectively. The grey correlative degree of SSW with other indexes was
      in the rank of F(v)/F(m), PMP, F(v)/F(o), RWC, MDA content, SOD activity,
      deltaF(v)/F(t), Chl content, and deltaF(v)/F(o).

PMID- 16964940
TI  - [Soil biological activities at maize seedling stage under application of
      slow/controlled release nitrogen fertilizers].
AB  - With pot experiment and simulating field ecological environment, this paper
      studied the effects of different slow/ controlled release N fertilizers on the
      soil nitrate - reductase and urease activities and microbial biomass C and N at
      maize seedling stage. The results showed that granular urea amended with
      dicyandiamide (DCD) and N-(n-bultyl) thiophosphoric triamide (NBPT) induced the
      highest soil nitrate-reductase activity, granular urea brought about the highest
      soil urease activity and microbial biomass C and N, while starch acetate (SA)
      coated granular urea, SA-coated granular urea amended with DCD, methyl
      methacrylate (MMA) -coated granular urea amended with DCD, and no N fertilization
      gave a higher soil urease activity. Soil microbial C and N had a similar
      variation trend after applying various kinds of test slow/controlled release N
      fertilizers, and were the lowest after applying SA-coated granular urea amended
      with DCD and NBPT. Coated granular urea amended with inhibitors had a stronger
      effect on soil biological activities than coated granular urea, and MMA-coating
      had a better effect than SA-coating.

PMID- 16964941
TI  - [Effects of allelopathic rice on rhizosphere microbial flora and enzyme
      activity].
AB  - This paper studied the dynamics of microbial flora and enzyme activity in the
      rhizosphere of allelopathic rice PI312777 (PI) and non-allelopathic rice Lemont
      (LE) at the growth stage of 3 - 7 leaves. The results showed that in the
      rhizosphere of PI, the amounts of bacteria, actinomycetes and azotobacter were
      11.2% - 28.3%, 40% - 78.6% and 111.5% - 173.9%, respectively, while that of fungi
      was lower, with the maximum being 25.5% of that in the rhizosphere of LE,
      suggesting that allelopathic rice PI promoted the growth of bacteria,
      actinomycetes and azotobacter, but inhibited that of fungi. Further analysis on
      the physiological groups of microbial flora showed that PI favored the growth of
      ammonifier, aerobic azotobacter, aerobic cellulose - decomposer, sulphate -
      reducer, nitrite - bacteria and nitrate - bacteria, among which, ammonifier and
      aerobic azotobacter increased by 53.7% and 57.6%, respectively, while inhibited
      the growth of desulphate bacteria and denitrifyier. Moreover, PI increased the
      activities of urease, phosphatase and sucrase, but decreased the catalase
      activity in its rhizosphere.

PMID- 16964942
TI  - [Feeding preference of Plutella xylostella (Lepidoptera: Plutellidae) larva to
      its hosts].
AB  - The feeding experiment with different sorts of Brassica vegetable crops showed
      that Plutella xylostella larva preferred the seedlings of Chinese cabbage
      (Brassica campestris L.), radish (Raphanus sativus L.) and caixin (Brassica
      campestris L.) to those of rape (Brassica napus L.) and cabbage (Brassica
      olereacea L.), with a selection proportion of 93.33% and 6.67% between Chinese
      cabbage and rape, and of 16.67% and 83.33% between cabbage and caixin. On the
      whole, the feeding preference of P. xylostella larva was less related to the
      contents of soluble glucide and starch in the vegetables, but had a definite
      negative correlation to the content ratio of these compounds. The P. xylostella
      larva fed with Chinese cabbage and caixin grew better than that fed with rape and
      cabbage, and the feeding amount and body weight of per larva were 0.583 - 0.637
      cm2 and 2.07 - 2.18 mg, respectively. The larva preferred damaged vegetable
      seedlings, too.

PMID- 16964943
TI  - [Electroantennogram and behavioral responses of Monochamus alternatus to the
      volatiles from Pinus thunbergii with different physiological status].
AB  - The volatiles from healthy and pinewood nematode-infested branches of Pinus
      thunbergii were collected by distillation, and analyzed by using HPLC and GC-MS.
      Electroantennogram (EAG) and behavioral responses of Monochamus alternatus with
      different physiological status to the volatiles were investigated respectively.
      The results showed that unmated beetle had a greater EAG response potential to
      the volatiles from healthy branch than to those from infested branch, while it
      was reverse for mated beetle. The EAG response of unmated beetle under 15 days
      old to the volatiles from healthy branch increased with its age. "Y" tube
      olfactory test showed unmated beetle had positive response to the volatiles from
      healthy branch and negative response to those from infested branch, while mated
      beetle showed positive response to the volatiles from infested branch and
      negative response to those from healthy branch. Female beetle with its age from 1
      day to 15 days-old and male beetle from 1 day to 9 days-old had an increasing
      positive response to the volatiles from healthy branch, but the male after 9 days
      old showed a negative response. It could be concluded that M. alternatus with
      different physiological status all had special sensitivity and selectivity to
      host tree.

PMID- 16964944
TI  - [Structural characteristics of arthropod community in grapery].
AB  - By the method of principal component analysis, this paper analyzed the
      characteristic parameters of arthropod community and its phytophagous and
      predacious sub-communities in grapery. The results showed that in the first
      principal component, the contribution of arthropod community, phytophagous sub
      community and predacious sub-community was 66.70%, 73.39% and 54.17%,
      respectively. For arthropod community, the absolute values of normalized
      regressive coefficients of individuals' number N, Hill diversity index N1, Hill
      diversity index N2 and McIntosh index D(mc) were larger, indicating their greater
      contribution on the community. For phytophagous sub-community, N, N1, N2, N and S
      (total species) had greater contribution; while for predacious sub-community, the
      greater contribution was made by N1, N2, Shannon-Wiener diversity index H' and
      abundance R. Synthetically, N2 and N1 had greater contribution on the arthropod
      community and its phytophagous and predacious sub-communities in grapery,
      comparing with other characteristic parameters.

PMID- 16964945
TI  - [Pb-tolerance of ectomycorrhizal fungi from polluted and unpolluted sites under
      different P levels].
AB  - By the method of liquid culture, this paper studied the effects of different P
      and Pb doses on the biomass production of three strains of ectomycorrhizal fungi,
      and the P and Pb concentrations in their mycelium. The results showed that under
      the application of P and Pb, the biomass production of strains ZC1 and ZC2,
      collected from mining area was significantly higher than that of strain GV
      collected from non-polluted site. At low P level (0.16 mmol x L(-1)), the growth
      of these three ectomycorrhizal fungi was inhibited by the increasing dose of Pb;
      while at higher P levels (0.81and 2.42 mmol x L(-1)), increasing dose of Pb
      inhibited the growth of GV significantly, but had little effects on ZC1 and ZC2.
      In all treatments, the Pb concentration in GV mycelia was significantly higher
      than that in the mycelia of ZC1 and ZC2. Under the same dose of Pb, the P
      concentration in GV mycelia was higher at low P level, but lower at higher P
      levels than that in ZC1 and ZC2 mycelia. The increase of Pb dose decreased the P
      concentration in ZC1 and ZC2, mycelia, but had little effect on that in GV
      mycelia. In comparing with GV, ZC1 and ZC2 had the characteristics of fast growth
      and low Pb and high P accumulation in their mycelia, indicating that the strains
      of ecomycorrhizal fungi collected from polluted area had a higher tolerance to
      environmental stress.

PMID- 16964946
TI  - [Hydrolysis characteristics of enrofloxacin].
AB  - By the method of high-performance liquid chromatography (HPLC), this paper
      studied the hydrolysis characteristics of enrofloxacin under conditions of
      different pH, light, and microorganism to assess its ecological risk. The results
      showed that no ciprofloxacin was found in the hydrolyzed products of
      enrofloxacin. Under the conditions of 50 degrees C and pH 1 - 10, the
      hydrolyzation rate of enrofloxacin was less than 10% within 5 days. The half-life
      of enrofloxacin was longer than one year at normal temperature and in dark, and
      buffer's pH had no significant effects on the hydrolysis of enrofloxacin. The
      degradation of enrofloxacin in natural water was strongly affected by light.
      Under outdoor natural light condition, enrofloxacin degraded quickly and was not
      examined after 3 days; while under indoor natural light condition, it degraded
      slowly, with the degradation rate being 48%, 72% and 65% after 31 days when its
      initial concentration in water was 0.05, 0.2 and 1.0 mg x L(-1), respectively.
      Enrofloxacin was very steady in dark, and microorganisms had no significant
      effects on its degradation. Owing its rapid degradation under outdoor natural
      light condition, enrofloxacin might have no direct harmfulness to aquatic
      ecosystem, but its potential ecological risk should not be neglected once
      entering into aquatic ecosystem, especially in bottom mud.

PMID- 16964947
TI  - [Photochemical degradation of chlorothalonil in aqueous solution].
AB  - The study on the effects of light source, solution pH and temperature, and
      surfactant on the photochemical degradation of chlorothalonil showed that the
      half-life of chlorothalonil photodegradation under high pressure mercury lamp
      (HPML), UV lamp and sunlight was 22.4, 82.5 and 123.8 min, respectively. Under
      HPML and sunlight, chlorothalonil had a higher photolysis rate in alkaline
      solution than in neutral and acid solution. The photolysis rate increased with
      increasing solution temperature in the range of 10 degrees C - 40 degrees C,
      which was doubled when the temperature increased every 10 degrees C. Sodium
      laurylsulfonate (SDS), sodium dodecylbenzene sulfonate (SDBS), Tween 60 and Span
      20 showed significant photosensitizing effects, while cetyltrimethylammonium
      bromide (CTAB) had significant photoquench effect on the photolysis of
      chlorothalonil.

PMID- 16964948
TI  - [Responses of different Vicia faba varieties' photosynthetic characteristics to
      Pb pollution].
AB  - In a field experiment of simulated Pb pollution (40 and 250 mg x kg(-1)), this
      paper investigated the net photosynthetic rate, stomal conductance, transpiration
      rate, intercellular CO2 concentration, water use efficiency, and chlorophyll
      content of three Vicia faba varieties K0883, K0502 and K0697. The results showed
      that under Pb pollution, there was no significant variation in the transpiration
      rate and stomal conductance of the three varieties, but their chlorophyll content
      increased in different extents. When the Pb concentration was 250 mg x kg(-1),
      the net photosynthetic rate and water use efficiency of K0883 were increased by
      121.80% and 193.70%, respectively, while its intercellular CO2 concentration was
      decreased by 42.76%. According to the Perturbation test based on the responses of
      test photosynthetic characteristics, the Pb-resistance of the three varieties was
      in the sequence of K0883 > K0697 > K0502. It was concluded that the responses of
      different photosynthetic indexes and different Vicia faba varieties to small
      dosage Pb pollution were differed, and the intraspecific difference could only be
      detected by the integration of all photosynthetic indices.

PMID- 16964949
TI  - [Atmospheric nitrogen wet deposition and its effects on wetland water environment
      of Shanghai area].
AB  - Based on the observation data of the rainfall and its NO3 (-) -N and NH4 (+) -N
      concentrations in Shanghai area from 1998 to 2003, and by the method of single
      factor evaluation, this paper studied the flux of atmospheric nitrogen wet
      deposition and its effects on wetland water environment of this area. The results
      showed that in the six years, the nitrogen content in the rainwater was rather
      high, with an average concentration of NO3 (-) -N and NH4 (+) -N being 2.59 mg x
      L(-1) and 2.16 mg x L(-1), respectively, and a total inorganic nitrogen of 4.74
      mg x L(-1), which exceeded the water eutrophication level (0.2 mg x L(-1)).
      According to the nitrogen concentration, the rainwater belonged to V and inferior
      V types of surface water quality. The nitrogen flux by wet deposition in the six
      years was 58.1 kg x hm(-2) x yr(-1), among which, NO3 (-) -N accounted for 54%.
      The effects of atmospheric nitrogen wet deposition on the eutrophication of the
      wetland water environment should be paid more attention.

PMID- 16964950
TI  - [Tolerance of Craspedacusta sowerbyi xinyangensis to the stresses of some
      ecological factors].
AB  - This paper studied the tolerance of Craspedacusta sowerbyi xinyangensis to the
      stresses of temperature, salinity, and pH from the aspects of its living status,
      morphology and survival, and measured its oxygen consumption rate and oxygen
      tolerance at different temperatures. The results indicated that the suitable
      temperature and pH of C. sowerbyi xinyangensis were 15 degrees C - 25 degrees C
      and 6.0 - 8.2, respectively. C. sowerbyi xinyangensi had a low tolerance to
      salinity, and it could only survive for 96 h when the salinity was 2. C. sowerbyi
      xinyangensi could bear low DO, and its lethal DO was 0.26 mg x L(-1) at 20
      degrees C. The average oxygen consumption amount and rate of C. sowerbyi
      xinyangensi increased with increasing temperature.

PMID- 16964951
TI  - [Mass-balance ecopath model of Belbu Gulf ecosystem].
AB  - Based on the investigation of fishery resources and eco-environment in the Beibu
      Gulf of northern South China Sea from October 1997 to May 1999, and with EwE
      software, a mass-balance ecopath model of Beibu Gulf ecosystem was constructed,
      which consisted of 16 functional groups (boxes) including marine mammals and
      seabirds, each representing the organisms with similar roles in the food web, and
      covered the main trophic flow in Beibu Gulf ecosystem. The food web in Beibu Gulf
      ecosystem was dominated by detrital path, and benthic invertebrate played a
      significant role in transferring energy from detritus to higher trophic levels.
      Phytoplankton was the primary producer, and the fractional trophic levels ranged
      from 1.00 to 4.04, with marine mammals occupying the highest trophic level. By
      using network analysis, the system network was mapped into a linear food chain,
      and six discrete trophic levels were found, with a mean transfer efficiency of
      12.3% from detritus, and 12.2% from primary producer within the ecosystem. The
      biomass density of commercially utilized species estimated by the model was 8.7 t
      x km(-2), and the bioproduction only accounted for 1.81% of the net primary
      production, which indicated that the system was still in developing status and
      instable.

PMID- 16964953
TI  - [Research advances in thermotolerance regulation of cool-season turfgrass].
AB  - Among abiotic stresses, high temperature is one of the important ecological
      factors limiting the growth and development of cool-season turfgrass in the
      transitional and warm climatic regions, especially during hot summer, which leads
      to the decline of turf quality, loss of chlorophyll, metamorphism of protein,
      decrease of photosynthetic activities, and even, cell death. Therefore, how to
      overcome the difficulty for cool-season turfgrass in spending hot summer
      successfully, especially in the transitional and warm climatic regions, is a
      serious problem. Based on the statement of regulation principle in
      thermotolerance, the research advances in thermotolerance regulation of cool
      season turfgrass were reported, including the advances in morphological,
      ecological, physiological, and biochemical characters in thermotolerance, and the
      advances in thermotolerance regulation by proper management and regulation
      measurements such as lowing the soil temperature, application of growth
      regulators and fertilization, proper clipping, and irrigation.

PMID- 16964952
TI  - [Molecular mechanisms of plant resistance to cadmium toxicity].
AB  - Cadmium (Cd) is a non-essential trace element for plants, and has strong toxicity
      at low concentrations. It can suppress the elongation growth of plant cell,
      inhibit oxidative mitochondrial phosphorylation, induce oxidative stress, inhibit
      the activities of several antioxidative enzymes, affect photosynthesis by
      inhibiting ferrous reductase or damaging photosynthesis apparatus, and cause the
      alteration of chromatin and the change of plasma membrane ATPase activity. In
      response to Cd stress, the cells of cadmium-resistant plant species can produce a
      number of proteins such as phytochelatins, metallothioneins and stress proteins
      to detoxify Cd ions, and efficiently repair Cd damage. The plant cells can also
      resort to other defense systems to detoxify Cd ions, e.g., the immobilization of
      Cd by cell wall, exclusion of Cd through the action of plasma membrane,
      compartmentalization of Cd by vacuolar, and release of plant glands. The
      phytochelatin synthase (PCS) genes of Arabidopsin, wheat and Schizosaccharomyces
      pombe had been identified by using different approaches, and the metallothioneins
      (MT) in plants was also identified recently. By introducing animal MT genes,
      transgenic plants could increase the resistant ability to Cd toxicity. Subjected
      to Cd, plant cells often start to synthesize stress proteins such as heat shock
      proteins, and the plants having been transformed the stress protein genes could
      enhance their resistant capacity to Cd ions. It was reported that zinc (Zn) ion
      transporting proteins could also transport Cd ion. Some minor genes not
      conferring tolerance on their own could modify the major gene (s), and enhance Cd
      tolerance. Cd detoxification in wild type plants could be a complex phenomenon,
      probably under polygenic control to Cd, while acute Cd stress seemed to be a
      simpler mechanism, apparently involving only one or a few specific major genes.

PMID- 16964954
TI  - [Application of organic agents in remediation of heavy metals- contaminated
      soil].
AB  - Organic agents play an important role in the remediation of heavy metals -
      contaminated soil, and their introduction into practice is a promising strategy
      to develop an efficient solution for this remediation. This paper summarized the
      research advances in the application of organic agents to the remediation of
      heavy metals- polluted soil, including their action mechanisms, advantages and
      disadvantages, and factors affecting their efficiency. The commonly used organic
      agents, such as aminopolycarboxylic acid, organic acid, humic acid,
      biosurfactants, etc., were introduced, and the prospects of organic agents'
      application were discussed.

PMID- 16964955
TI  - [Soil microbial ecological process and microbial functional gene diversity].
AB  - Soil microbes in terrestrial ecosystem carry out a series of important ecological
      functions, such as geo-chemical cycling of elements, degradation of pollutants,
      and buffering to the acute changes of environment, etc. Soil microbial ecological
      function has a close relation with soil function, and the changes in the
      structure and composition of soil microbial populations can directly affect the
      realization of soil function. Through their produced enzymes, soil microbes take
      part in a series of metabolic activities, and the functional genes of coded
      enzymes are the functional markers of microbes. In recent ten years, molecular
      ecology focusing on the functional gene diversity has been developed rapidly,
      which gives us a new cut-in point to understand soil microbial ecological
      function from the point of functional gene. This paper reviewed the research
      advances in the functional gene diversity correlated to soil microbial ecological
      function, with the perspectives in this field discussed.

PMID- 16964956
TI  - [Cold tolerance and its seasonal variation of Catantops pinguis Stal].
AB  - By the method of supercooling point (SCP) determination, this paper studied the
      cold tolerance of Catantops pinguis Stal in different seasons, and the effects of
      insect body water content, crude fat, total protein and total sugar on it. The
      results showed that there was a significant seasonal variation in the SCP of C.
      pinguis. The mean SCP value of fall C. pinguis population was (-23.1 +/- 0.2)
      degrees C, while that of post-winter and summer C. pinguis populations was (-19.3
      +/- 0.1) degrees C and (-4.0 +/- 0.1) degrees C, respectively. The water content
      in summer population was significantly higher than that in winter population, but
      little difference was observed in fall and post-winter populations, indicating
      that C. pinguis had eliminated the redundant dissociate water during the
      preparation period for its over-wintering. After winter, the contents of fat and
      sugar in C. pinguis decreased significantly because the storage of these
      compounds was expended to maintain the body temperature at winter time, and
      consequently, resulted in a marked increase of SCP in post-winter population.
      There was no significant difference in the contents of water and crude fat
      between female and male C. pinguis, but the total protein content of female C.
      pinguis was higher than that of male C. pinguis in summer while significantly
      lower in winter, because large amount of nutrients was expended by the female C.
      pinguis to form eggs.

PMID- 16964957
TI  - [Inhibitory effects of natural plant extracts on Verticillium albo-atrum].
AB  - This paper studied the inhibitory effects of 54 kinds of ethanol-extracted plant
      solutions on Verticillium albo-atrum. The results showed that 15 kinds of these
      extracts could inhibit the growth of verticillium albo-atrum mycelium, with an
      inhibitory rate more than 50%, among which, the inhibitory rate of Asarum
      sieboldii, Coptis chinensis, Magnolia officinalis, Acacia catechu, Sophora
      flavescens, Glycyrrhiza uralensis, Cnidium monnieri, Platycodon grandiflorum and
      Allium. cepa. extracts was higher than 65%, and that of Cnidium monnieri extract
      reached 86.84%. A total of 16 kinds of plant extracts decreased the spore
      germination of V. albo-atrum, with the inhibitory rate higher than 70%, and there
      were 7 kinds of plant extracts whose inhibitory rate reached 95%. Almost no spore
      bourgeon was found after treated with Asarum sieboldii, Coptis chinensis, and
      Magnolia officinalis extracts. The extract of Acacia catechu did not inhibit the
      growth of mycelium, but restrained the spore germination by 100%. Cnidium
      monnieri extract could strongly inhibit the growth of mycelium, but had a less
      effect on spore germination rate (only by 11.3%). The active substances found in
      natural plant extracts which had the inhibitory effects on pathogen brought us a
      new and promising method to deal with V. albo-atrum and other vegetable diseases.

PMID- 16964958
TI  - [Effects of Apatococcus lobatus parasitization on leaf photosynthesis
      characteristics of orange (Citrus cv. Olinda)].
AB  - With 2-year pot-grown grafted Citrus cv. Olinda as test material, this paper
      studied the effects of Apatococcus lobatus parasitization on its leaf
      photosynthesis characteristics. No significant differences were observed between
      slightly affected and control leaves in their total chlorophyll (Chl a + b) and
      carotenoid (Car) contents, net photosynthetic rate (P(n)), intercellular CO2
      concentration (C(i)), primary maximum photochemical efficiency of PS II
      (F(v)/F(m)), quantum efficiency of noncyclic electron transport of PS II (phiPS
      II), and photochemical quenching (qP), but for medium and severely affected
      leaves, their Chl a + b, Car, P(n), F(v)/F(m), phiPS II and qP decreased by
      23.85%, 26.49%, 43.3%, 4.5%, 35.1% and 22.5%, and 37.61%, 44.04%, 64.5%, 8.6%,
      63.6% and 40.1%, respectively, while C(i) increased, with significant differences
      to the control. It could be concluded that the massive parasitization of A.
      lobatus caused a stress to orange plant, and non-stomatal limitation was the
      dominating factor of P(n) reduction.

PMID- 16964959
TI  - [Effects of Larix gmelini aqueous extracts on seed germination and seedling
      growth of Juglans mandshurica].
AB  - In this study, Juglans mandshurica seeds were drenched in different
      concentrations (12.5, 25, 50 and 100 g x kg(-1)) aqueous extracts from adult
      Larix gmelini root, bark, branch and leaf for one week, and cultured in
      greenhouse in mid-April, 2004. The germination rate and germination index were
      calculated 18 days later, and the seedling's height and collar diameter were
      measured on August 1st. The results suggested that 25 g x kg(-1) root and 12.5 g
      x kg(-1) bark and branch aqueous extracts of L. gmelini could significantly
      increase the seed germination rate and germination index of J. mandshurica (P <
      0.05), and 12.5 g x kg(-1) root and bark aqueous extracts could significantly
      increase the seedling height and collar diameter (P < 0.05). High concentrations
      of L. gmelini leaf aqueous extract could significantly promote the seed
      germination and seedling growth of J. mandshurica, but the promotion effect
      decreased gradually with decreasing concentration of leaf aqueous extract. The
      promotion of L. gmelini aqueous extracts to J. mandshurica seed germination and
      seedling growth might be related to the allelopathy between these two tree
      species.

PMID- 16964960
TI  - New tricks for living past 96.

PMID- 16964961
TI  - Associations between HLA class II alleles and type 1 diabetes mellitus in the
      Slovak population.
AB  - OBJECTIVES: Several associations between HLA complex and diabetes mellitus type
      IA were found in various groups of patients of Caucasoid population. This study
      was therefore prompted to be conducted in Slovak population, since any such has
      not yet been performed in Slovak population. METHODS: Patients suffering from DM
      1A originated from all regions of Slovakia. Their age ranged from 1 to 42 years;
      but the criterion for including the subject to the study was the definition of
      diagnosis in older patients before their age of 15 (Table 1). The diagnosis was
      set up according to internationally accepted criteria. A total of 460 patients
      was typed for HLA-DQB1 alleles, among them 97 also for HLA-DQA1 and 146 for HLA
      DRB1 alleles. HLA-typing was performed by a PCR-SSP method. Control group
      consisted of 196 (DQA), 143 (DQB1) and 130 (DRB1) unrelated blood donors aged 19
      55 years old irrespective of their age or sex. The data obtained were expressed
      in a 2 x 2 contingency table and statistical significance was calculated by the
      Fisher exact test. RESULTS: Among 11 HLA-DQB1 alleles tested DOB1*0302 was the
      most frequent in DM-1A patients (30.33% vs. 5.59% in healthy subjects (HS),
      followed by DQB1*0201 (22.93% vs. 12.94%, respectively). In contrast, the
      frequency rate of DQB1*0301 (10.66% vs. 24.48%), DOB1*0602 (2.17% vs. 10.14%) and
      DQB1*0603 (2.5% vs. 8.39 %) were decreased in DM-1A patients. Out of 14 DQA1
      alleles the highest occurrence rate showed DQA1*0301 (30.93% vs. 17.09) and
      DQA1*0501 (34.02% vs. 25.76%), while DQA1*0102 (8.76% vs. 16.58%) and DQA1*0201
      (6.18 % vs. 13.51%7), respectively, were found to be the least frequent. Among 13
      HLA-DRB1 alleles tested, the most common occurrence rates showed DRB1*03 (26.37%
      vs. 9.62%) and DRB1*04 (7.19% vs. 14.23%), while the least frequent alleles were
      DRB 1*15 (2.74% vs. 12.31%), DRB1*07 (7.19% vs. 14.23%), and DRB1*11 (2.74% vs.
      20.38%). The alleles DQB1*0302 and DQA1*0301, respectively, were present in the
      same individual in all DRB1*04 positive patients, suggesting that they belong to
      the haplotype. Similar situation was observed with the alleles DQB1*0201,
      DQA1*0501, and DRB*0301, respectively, forming the second HLA haplotype so
      characteristic for DM1A.

PMID- 16964962
TI  - Analysis of physical and mental development of children with aplasia, hypoplasia
      and ectopy of the thyroid gland.
AB  - OBJECTIVE: Evaluation of clinical and biochemical differences between various
      forms of thyroid dysgenesia in children. METHODS: The study involved 102 children
      at the age between 4.8 and 14.2 years who were born with congenital
      hypothyroidism (CH), as diagnosed by neonatal screening examinations. In all the
      children diagnosis was settled and the levothyroxine (L-T4) administration was
      started by the 19th day of life. Out of the examined children, 79 were selected
      with following three forms of developmental thyroid disorders: Group I-
      athyroidism (thyroid aplasia or agenesis), Group II--thyroid hypoplasia, Group
      III--thyroid ectopy. On the basis of neonatal TSH (nTSH) levels obtained by
      screening and serum TSH, FT4 and Tg concentrations, the severity of
      hypothyroidism was determined at the time of diagnosis. Physical and mental
      development of the children was evaluated on the basis of growth and bone age
      indices and Wechsler's scale, respectively. RESULTS: Developmental disorders were
      diagnosed in 79 cases (77.4% CH) which included 45 cases (44.1%) of athyroidism,
      31 cases (30.4%) of thyroid hypoplasia and 3 cases (2.9%) of thyroid ectopy. The
      physical and mental development in the studied groups was evaluated as normal.
      CONCLUSIONS: In the group of children with athyroidism, significantly lower
      growth indices and IQ values were found in comparison with respective values
      observed in the other study groups. However, the indices of physical and mental
      development in all the studied groups were within the normal values for children
      population. An early diagnosis and early administration of hormonal replacement
      therapy by L-T4 ensure normal development of children with CH, regardless of
      underlying causes and associated with them severity of congenital hypothyroidism.

PMID- 16964963
TI  - Adiponectin as a biomarker of clinical manifestation of metabolic syndrome.
AB  - OBJECTIVES: To search whether there are differences in serum levels of
      adiponectin in subjects with metabolic syndrome (MS) as compared to the healthy
      controls. METHODS: Serum levels of adiponectin were measured by ELISA in 22
      subjects with MS (MS group: 9 males and 13 females, average age +/- SD 43.19 +/-
      6.16) and in 17 healthy controls of about the same age (CONT group: 8 males and 9
      females, average age +/- SD 45.88 +/- 11.6). All subjects of MS group had BMI >30
      and also other criteria of MS (e.g. obesity, insulin resistance, possible
      disorders of glucose metabolism, dyslipidemia and hypertension) were manifested
      in all of them. Adiponectin levels in serum were compared between the groups and
      also within the pooled MS plus CONT group the interrelations between serum levels
      of adiponectin and BMI, serum fasting insulin (estimated by RIA method) and
      smoking were examined. For statistical processing one way ANOVA or its non
      parametric parallel (Kruskal-Wallis one-way analysis) as well as regression and
      correlation analysis were used. RESULTS: Subjects with MS syndrome had
      significantly higher BMI, systolic and diastolic BP, fasting glycemia and insulin
      level. Significantly higher were also the values of both indexes of insulin
      resistance such as IR(HOMA) and IR(QUlCKI). In contrast, however, MS group had
      significantly lower adiponectin level than CONT group. There was no difference
      between the average age of both groups. In pooled MS plus CONT group inverse
      correlations were found between serum levels of adiponectin on one side and BMI
      and fasting insulin level on the other, while the level of adiponectin between
      smokers (which was declared by 18/39 subjects) and non-smokers did not show any
      influence on serum levels of adiponectin. CONCLUSIONS: Low level of adiponectin
      in obese individuals may be considered as a marker predicting a possibility of
      the development of metabolic syndrome. It is suggested that early regulation of
      serum adiponectin levels in obese subjects by treatment of obesity, especially in
      young ones, could result in a lowering the risk of mainly cardiovascular diseases
      associated with MS.

PMID- 16964964
TI  - Binding of doa kinase to specific loci in polytene chromosomes of Drosophila
      melanogaster.
AB  - OBJECTIVES: Highly conserved LAMMER kinases belong to the family of dual-specific
      proteins phosphorylating enzymes with homologues in yeast, plants, Drosophila and
      mammals. SR proteins, several members of which are components of the spliceosomal
      complex and have been implicated in the control of alternative splicing, were
      identified among first targets of LAMMER kinases. The Drosophila locus Darkener
      of apricot (Doa) encodes best known representative of the LAMMER family of
      kinases, which is essential for embryonic and postembryonic development,
      neurogenesis, differentiation of photoreceptors, and sex determination. METHODS:
      DOA kinase was detected on squash preparations of polythene chromosomes using
      anti-DOA antibodies in combination with indirect immunofluorescence. RESULTS:
      Here we provide evidence for active chromosomal presence of DOA kinase in
      Drosophila salivary glands, and increased abundance of DOA at eleven specific
      loci of polythene chromosomes where it can be involved in on-site control of
      splicing process. Many genes that may be found at the loci with increased
      abundance fall into three major groups based on their known functions. First
      group contains genes that code for transcription factors, RNA-binding proteins or
      chromatin modifying enzymes. Second group of genes encode proteins which belong
      to proteasomal components, lipid enzymes, stress-sensitive ER proteins and
      caspases which are all early/proximal components of apoptotic process. Third
      group of genes comprises of tRNA coding genes or genes of tRNA synthases
      (ligases), all involved in protein synthesis. Some of the encoded protein
      products are confirmed or potential substrates of DOA kinase activity.
      CONCLUSIONS: Data indicate that genes encoding proteins involved in closely
      related pathways are concentrated at certain loci to achieve more efficient
      regulation of their expression as exemplified from distribution of DOA protein on
      Drosophila polythene chromosomes.

PMID- 16964965
TI  - Metabolism-independent sugar effects on gene transcription: the role of 3-O
      methylglucose.
AB  - Glucose effects on cellular functions such as gene expression require, in
      general, glucose metabolism at least to glucose-6-phosphate (G-6-P). However, the
      example of thioredoxin-interacting protein (TXNIP), a glucose-regulated gene
      involved in the cellular redox state and pancreatic beta cell apoptosis,
      demonstrates that this rule may not always apply. We found that aside form
      glucose, the nonmetabolizable sugars 2-deoxyglucose, which is still converted to
      G-6-P as well as 3-O-methylglucose (3-MG), which cannot be phosphorylated by
      glucokinase, stimulate TXNIP expression. In contrast, incubation of INS-1 beta
      cells with equimolar amounts (25 mM) of l-glucose or mannitol had no effect on
      TXNIP expression as measured by real-time RT-PCR, eliminating the possibility of
      an osmotic effect. Also, glucose uptake into the cell is critical because
      phloretin, an inhibitor of glucose transporter 2, blunted the glucose effects.
      Moreover, the 3-MG effect was not restricted to a cell line and was observed in
      293 cells and primary human islets. Incubation of INS-1 cells with 30mM
      mannoheptulose, an inhibitor of glucose metabolism, blunted all glucose-induced
      gene expression but left the 3-MG effects unaltered. Using transient transfection
      studies and deletion constructs of the human TXNIP promoter, we found that the
      effects of glucose and 3-MG were dependent on the same region of the TXNIP
      promoter containing an E-box repeat carbohydrate response element (ChoRE). Thus,
      these findings provide the first evidence for regulation of gene expression by 3
      MG, which is independent of glucose metabolism and suggest that glucose and 3-MG
      regulate transcription by two distinct pathways converging at a common ChoRE.

PMID- 16964966
TI  - X-ray crystallographic structure of the angiogenesis inhibitor, angiostatin,
      bound to a peptide from the group A streptococcal surface protein PAM.
AB  - The crystal structure of the human Pg-derived angiogenesis inhibitor,
      angiostatin, complexed to VEK-30, a peptide from the group A streptococcal
      surface protein, PAM, was determined and refined to 2.3 A resolution. This is the
      first structure of angiostatin bound to a ligand and provides a model of the
      interaction between Pg and streptococcal-derived pathogenic proteins. VEK-30
      contains a "through-space isostere" for C-terminal lysine, wherein Arg and Glu
      side chains, separated by one helical turn, bind within the bipolar angiostatin
      kringle 2 (K2) domain lysine-binding site. VEK-30 also makes several contacts
      with K2 residues that exist outside of the canonical LBS and are not conserved
      among the other Pg kringles, thus providing a molecular basis for the selectivity
      of VEK-30 for K2. The structure also shows that Pg kringle domains undergo
      significant structural rearrangement relative to one another and reveals
      dimerization between two molecules of angiostatin and VEK-30 related by
      crystallographic symmetry. This dimerization, which exists only in the crystal
      structure, is consistent with the parallel coiled-coil full-length PAM dimer
      expected from sequence similarities and homology modeling.

PMID- 16964967
TI  - Structural insights into the function of the thiamin biosynthetic enzyme Thi4
      from Saccharomyces cerevisiae.
AB  - The structure of thiazole synthase (Thi4) from Saccharomyces cerevisiae was
      determined to 1.8 A resolution. Thi4 exists as an octamer with two monomers in
      the asymmetric unit. The structure reveals the presence of a tightly bound
      adenosine diphospho-5-(beta-ethyl)-4-methylthiazole-2-carboxylic acid at the
      active site. The isolation of this reaction product identifies NAD as the most
      likely precursor and provides the first mechanistic insights into the
      biosynthesis of the thiamin thiazole in eukaryotes. Additionally, the Thi4
      structure reveals the first protein structure with a GR(2) domain that binds NAD
      instead of FAD, raising interesting questions about how this protein evolved from
      a flavoenzyme to a NAD binding enzyme.

PMID- 16964968
TI  - Kinetic and structural insight into the mechanism of BphD, a C-C bond hydrolase
      from the biphenyl degradation pathway.
AB  - Kinetic and structural analyses of 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid
      (HOPDA) hydrolase from Burkholderia xenovorans LB400 (BphD(LB400)) provide
      insight into the catalytic mechanism of this unusual serine hydrolase. Single
      turnover stopped-flow analysis at 25 degrees C showed that the enzyme rapidly
      (1/tau(1) approximately 500 s(-1)) transforms HOPDA (lambda(max) = 434 nm) into a
      species with electronic absorption maxima at 473 and 492 nm. The absorbance of
      this enzyme-bound species (E:S) decayed in a biphasic manner (1/tau(2) = 54 s(
      1), 1/tau(3) = 6 s(-1) approximately k(cat)) with simultaneous biphasic
      appearance (48 and 8 s(-1)) of an absorbance band at 270 nm characteristic of one
      of the products, 2-hydroxypenta-2,4-dienoic acid (HPD). Increasing solution
      viscosity with glycerol slowed 1/tau(1) and 1/tau(2) but affected neither
      1/tau(3) nor k(cat), suggesting that 1/tau(2) may reflect diffusive HPD
      dissociation, and 1/tau(3) represents an intramolecular event. Product inhibition
      studies suggested that the other product, benzoate, is released after HPD.
      Contrary to studies in a related hydrolase, we found no evidence that ketonized
      HOPDA is partially released prior to hydrolysis, and, therefore, postulate that
      the biphasic kinetics reflect one of two mechanisms, pending assignment of E:S
      (lambda(max) = 492 nm). The crystal structures of the wild type, the S112C
      variant, and S112C incubated with HOPDA were each determined to 1.6 A resolution.
      The latter reveals interactions between conserved active site residues and the
      dienoate moiety of the substrate. Most notably, the catalytic residue His265 is
      hydrogen-bonded to the 2-hydroxy/oxo substituent of HOPDA, consistent with a role
      in catalyzing ketonization. The data are more consistent with an acyl-enzyme
      mechanism than with the formation of a gem-diol intermediate.

PMID- 16964969
TI  - HscA and HscB stimulate [2Fe-2S] cluster transfer from IscU to apoferredoxin in
      an ATP-dependent reaction.
AB  - The role of the Azotobacter vinelandii HscA/HscB cochaperone system in ISC
      mediated iron-sulfur cluster biogenesis has been investigated in vitro by using
      CD and EPR spectrometry to monitor the effect of HscA, HscB, MgATP, and MgADP on
      the time course of cluster transfer from [2Fe-2S]IscU to apo-Isc ferredoxin. CD
      spectra indicate that both HscB and HscA interact with [2Fe-2S]IscU and the rate
      of cluster transfer was stimulated more than 20-fold in the presence
      stoichiometric HscA and HscB and excess MgATP. No stimulation was observed in the
      absence of either HscB or MgATP, and cluster transfer was found to be an ATP
      dependent reaction based on concomitant phosphate production and the enhanced
      rates of cluster transfer in the presence of KCl which is known to stimulate HscA
      ATPase activity. The results demonstrate a role of the ISC HscA/HscB cochaperone
      system in facilitating efficient [2Fe-2S] cluster transfer from the IscU scaffold
      protein to acceptor proteins and that [2Fe-2S] cluster transfer from IscU is an
      ATP-dependent process. The data are consistent with the proposed regulation of
      the HscA ATPase cycle by HscB and IscU [Silberg, J. J., Tapley, T. L., Hoff, K.
      G., and Vickery, L. E. (2004) J. Biol. Chem. 279, 53924-53931], and mechanistic
      proposals for coupling of the HscA ATPase cycle with cluster transfer from [2Fe
      2S]IscU to apo-IscFdx are discussed.

PMID- 16964970
TI  - Periplasmic metal-resistance protein CusF exhibits high affinity and specificity
      for both CuI and AgI.
AB  - The periplasmic protein CusF, as a part of the CusCFBA efflux complex, plays a
      role in resistance to elevated levels of copper and silver in Escherichia coli.
      Although homologues have been identified in other Gram-negative bacteria, the
      substrate of CusF and its precise role in metal resistance have not been
      described. Here, isothermal titration calorimetry (ITC) was used to demonstrate
      that CusF binds with high affinity to both Cu(I) and Ag(I) but not Cu(II). The
      affinity of CusF for Ag(I) was higher than that for Cu(I), which could reflect
      more efficient detoxification of Ag(I) given the lack of a cellular need for
      Ag(I). The chemical shifts in the nuclear magnetic resonance (NMR) spectra of
      CusF-Ag(I) as compared to apo-CusF show that the region of CusF most affected by
      Ag(I) binding encompasses three absolutely conserved residues: H36, M47, and M49.
      This suggests that these residues may play a role in Ag(I) coordination. The NMR
      spectra of CusF in the presence of Cu(II) do not indicate specific binding, which
      is in agreement with the ITC data. We conclude that Cu(I) and Ag(I) are the
      likely physiological substrates.

PMID- 16964971
TI  - Luciferin derivatives for enhanced in vitro and in vivo bioluminescence assays.
AB  - In vivo bioluminescence imaging has become a cornerstone technology for
      preclinical molecular imaging. This imaging method is based on light-emitting
      enzymes, luciferases, which require specific substrates for light production.
      When linked to a specific biological process in an animal model of human biology
      or disease, the enzyme-substrate interactions become biological indicators that
      can be studied noninvasively in living animals. Signal intensity in these animal
      models depends on the availability of the substrate for the reaction within
      living cells in intact organs. The biodistribution and clearance rates of the
      substrates are therefore directly related to optimal imaging times and signal
      intensities and ultimately determine the sensitivity of detection and
      predictability of the model. Modifications of d-luciferin, the substrate for the
      luciferases obtained from beetle, including fireflies, result in novel properties
      and offer opportunities for improved bioassays. For this purpose, we have
      synthesized a conjugate, glycine-d-aminoluciferin, and investigated its
      properties relative to those of d-aminoluciferin and d-luciferin. The three
      substrates exhibited different kinetic properties and different intracellular
      accumulation profiles due to differences in their molecular structure, which in
      turn influenced their biodistribution in animals. Glycine-d-aminoluciferin had a
      longer in vivo circulation time than the other two substrates. The ability to
      assay luciferase in vitro and in vivo using these substrates, which exhibit
      different pharmacokinetic and pharmacodynamic properties, will provide
      flexibility and improve current imaging capabilities.

PMID- 16964972
TI  - C-terminal analogues of parathyroid hormone: effect of C-terminus function on
      helical structure, stability, and bioactivity.
AB  - We have studied the effects of C-terminal group modifications (amide,
      methylamide, dimethylamide, aldehyde, and alcohol) on the conformation, adenylyl
      cyclase stimulation (AC), or binding of parathyroid hormone (hPTH) analogues,
      hPTH(1-28)NH(2) and hPTH(1-31)NH(2). hPTH(1-31)NH(2) has a C-terminal alpha-helix
      bounded by residues 17-29 [Chen, Z., et al. (2000) Biochemistry 39, 12766]. In
      both cases, relative to the natural analogue with a carboxyl C-terminus, the
      amide and methylamide had increased helix content whereas the dimethylamide forms
      had CD spectra more similar to the carboxyl one. Conformational effects were more
      pronounced with hPTH(1-28) than with hPTH(1-31), with increases in helix content
      of approximately 30% in contrast to 10%. Stabilization of the C-terminal helix of
      residues 1-28 seemed to correlate with an ability of the C-terminal function to H
      bond appropriately. None of the analogues affected the AC stimulating activity
      significantly, but there was an up to 15-fold decrease in the level of apparent
      binding of the carboxyl hPTH(1-28) analogue compared to that of the methylamide
      and a 4-fold decrease in the level of binding of the aldehyde or dimethylamide.
      There was no significant change in binding activities for the 1-31 analogues.
      These observations are consistent with previous studies that imply the importance
      of a region of the hormone's C-terminal alpha-helix for tight binding to the
      receptor. They also show that modulation of helix stability does have an effect
      on the binding of the hormone, but only when the C-terminus is at the putative
      end of the helix. The similarity of AC stimulation even when binding changed 10
      fold can be explained by assuming greater efficacy of the weaker binding PTH
      receptor complexes in stimulating AC.

PMID- 16964973
TI  - The role of an extra fragment of cytochrome b (residues 309-326) in the
      cytochrome bc1 complex from Rhodobacter sphaeroides.
AB  - In bacterial cytochrome b of the cytochrome bc(1) complex, there is an extra
      fragment located between the amphipathic helix ef and the transmembrane helix F
      compared to the mitochondrial counterparts. In this work, mutants at various
      positions of this extra fragment were generated in Rhodobacter sphaeroides in an
      effort to investigate its specific role in the bacterial bc(1) complex. The total
      deletion [cytb-Delta(309-326)] and alanine substitution [cytb-(309-326)A] mutant
      complexes have about 20% of the bc(1) activity found in the wild-type complex.
      Mutant complexes of cytb-(309-311)A, cytb-(312-314)A, cytb-(315-317)A, cytb-(318
      321)A, cytb-(322-323)A, cytb-(324-326)A, cytb-(F323A), and cytb-(S322A) have
      respectively 87%, 85%, 89%, 100%, 32%, 90%, 100%, and 32% of the bc(1) activity,
      indicating that the S322 of cytochrome b is important. EPR spectral analysis
      reveals that the [2Fe-2S] cluster in the cytb-(S322A) mutant complex has a
      broadened and shifted g(x)() signal (g = 1.76). The rate of superoxide anion
      (O(2)(*)(-)) generation is 4 times higher in the cytb-(S322A) mutant complex than
      in the wild-type or mutant complexes of S322T, S322Y, or S322C. These results
      support the idea that alanine substitution at S322 of cytochrome b causes
      conformational changes at the Q(o) site by weakening the binding between
      cytochrome b and ISP through hydrogen bonding provided by the hydroxyl group of
      this residue. This change facilitates electron leakage from the Q(o) site for
      reaction with molecular oxygen to form superoxide anion, thus decreasing bc(1)
      activity.

PMID- 16964974
TI  - The catalytic machinery of chondroitinase ABC I utilizes a calcium coordination
      strategy to optimally process dermatan sulfate.
AB  - The chondroitinases are bacterial lyases that specifically cleave chondroitin
      sulfate and/or dermatan sulfate glycosaminoglycans. One of these enzymes,
      chondroitinase ABC I from Proteus vulgaris, has the broadest substrate
      specificity and has been widely used to depolymerize these glycosaminoglycans.
      Biochemical and structural studies to investigate the active site of
      chondroitinase ABC I have provided important insights into the catalytic amino
      acids. In this study, we demonstrate that calcium, a divalent ion, preferentially
      increases the activity of chondroitinase ABC I toward dermatan versus chondroitin
      substrates in a concentration-dependent manner. Through biochemical and
      biophysical investigations, we have established that chondroitinase ABC I binds
      calcium. Experiments using terbium, a fluorescent calcium analogue, confirm the
      specificity of this interaction. On the basis of theoretical structural models of
      the enzyme-substrate complexes, specific amino acids that could potentially play
      a role in calcium coordination were identified. These amino acids were
      investigated through site-directed mutagenesis studies and kinetic assays to
      identify possible mechanisms for calcium-mediated processing of the dermatan
      substrate in the active site of the enzyme.

PMID- 16964975
TI  - pH Dependence of peptidylglycine monooxygenase. Mechanistic implications of Cu
      methionine binding dynamics.
AB  - The pH dependence of the PHM-catalyzed monooxygenation of dansyl-YVG was studied
      in two different buffer systems in the pH range of 4-10. The pH-activity profile
      measured in a sulfonic acid buffer exhibited a maximum at pH 5.8 and became
      inactive at pH >9. The data could be fit to a model that assumed a protonated
      unreactive species A, a major reactive species B, and a less reactive species C.
      B formed in a deprotonation step with pK(a) of 4.6, while C formed and decayed
      with pK(a)s of 6.8 and 8.2, respectively. The pH dependence was found to be
      dominated by k(cat), with K(m)(dansyl-YVG) remaining pH-independent over the pH
      range of 5-8. Acetate-containing buffers shifted the pH maximum to 7.0, and the
      activity-pH profile could be simulated by formation and decay of a single active
      species with pK(a)s of 5.8 and 8.3, respectively. The pH-dependent changes in
      activity could be correlated with a change in the Debye-Waller factor for the Cu
      S(met) (M314) component of the X-ray absorption spectrum which underwent a
      transition from a tightly bound inactive "met-on" form to a conformationally
      mobile active "met-off" form with a pK(a) which tracked the formation of the
      active species in both sulfonic acid and acetate-containing buffer systems. The
      data suggested that the conformational mobility of the bound substrate relative
      to the copper-superoxo active species is critical to catalysis and further
      suggested the presence of an accessible vibrational mode coupling Cu-S motion to
      the H tunneling probability along the Cu-O...H...C coordinate.

PMID- 16964976
TI  - Mechanism of FAD reduction and role of active site residues His-225 and Tyr-259
      in Arthrobacter globiformis dimethylglycine oxidase: analysis of mutant structure
      and catalytic function.
AB  - Residues His-225 and Tyr-259 are located close to the FAD in the dehydrogenase
      active site of the bifunctional dimethylglycine oxidase (DMGO) of Arthrobacter
      globiformis. We have suggested [Leys, D., Basran, J., and Scrutton, N. S. (2003)
      EMBO J. 22, 4038-4048] that these residues are involved in abstraction of a
      proton from the substrate amine group of dimethylglycine prior to C-H bond
      breakage and FAD reduction. To investigate this proposal, we have isolated two
      mutant forms of DMGO in which (i) His-225 is replaced with Gln-225 (H225Q mutant)
      and (ii) Tyr-259 is replaced with Phe-259 (Y259F mutant). Both mutant enzymes
      retain the ability to oxidize substrate, but the steady-state turnover of the
      Y259F mutant is attenuated more than 200-fold. Only modest changes in kinetic
      parameters are observed for the H225Q mutant during steady-state turnover.
      Stopped-flow studies indicate that the rate of FAD reduction in the Y259F enzyme
      is substantially impaired by a factor of approximately 1500 compared with that of
      the wild-type enzyme, suggesting a key role for this residue in the reductive
      half-reaction of the enzyme. The kinetics of FAD reduction in the H225Q enzyme
      are complex and involve three discrete kinetic phases that are attributed to
      different conformational states of this mutant, evidence for which is provided by
      crystallographic analysis. Neither the H225Q enzyme nor the Y259F enzyme
      stabilizes the FADH(2)-iminium charge-transfer complex observed previously in
      stopped-flow studies with the wild-type enzyme. Our studies are consistent with a
      key role for Tyr-259, but not His-225, in deprotonation of the substrate amine
      group prior to FAD reduction. We infer that residue His-225 is likely to modulate
      the acid-base properties of Tyr-259 by perturbing the pK(a) of Tyr-259 and thus
      fine-tunes the reaction chemistry to facilitate proton abstraction under
      physiological conditions. Our data are discussed in the context of the
      crystallographic data for DMGO and also in relation to contemporary mechanisms
      for flavoprotein-catalyzed oxidation of amine substrates.

PMID- 16964977
TI  - Pairwise coupling analysis of helical junction hydrogen bonding interactions in
      luteoviral RNA pseudoknots.
AB  - A 28-nucleotide mRNA pseudoknot that overlaps the P1 and P2 genes of sugarcane
      yellow leaf virus (ScYLV) stimulates -1 ribosomal frameshifting. The in vitro
      frameshifting efficiency is decreased >or=8-fold upon substitution of the 3'-most
      loop 2 nucleotide (C27) with adenosine, which accepts a hydrogen bond from the 2'
      OH group of C14 in stem S1. The solution structures of the wild-type (WT) and
      C27A ScYLV RNA pseudoknots show that while the RNAs adopt virtually identical
      overall structures, there are significant structural differences at the helical
      junctions of the two RNAs. Specifically, C8(+) in loop L1 in the C8(+).(G12.C28)
      L1-S2 major groove base triple is displaced by approximately 2.3 A relative to
      the accepting stem 2 base pair (G12.C28) in the C27A RNA. Here, we use a double
      mutant cycle approach to analyze the pairwise coupling of the
      C8(+).(G12.C28)...C27.(C14-G7) and ...A27.(C14-G7) hydrogen bonds in the WT and
      C27A ScYLV RNAs, respectively, and compare these findings with previous results
      from the beet western yellows virus (BWYV) RNA. We find that the pairwise
      coupling free energy (delta(AB)(i)) is favorable for the WT RNA (-0.7 +/- 0.1
      kcal/mol), thus revealing that formation of these two hydrogen bonds is
      positively cooperative. In contrast, delta(AB)(i) is 0.9 +/- 0.4 kcal/mol for the
      poorly functional C27A ScYLV RNA, indicative of nonadditive hydrogen bond
      formation. These results reveal that cooperative hydrogen bond formation across
      the helical stem junction in H-type pseudoknots correlates with enhanced
      frameshift stimulation by luteoviral mRNA pseudoknots.

PMID- 16964978
TI  - Conserved conformation of RecA protein after executing the DNA strand-exchange
      reaction. A site-specific linear dichroism structure study.
AB  - RecA protein and its eukaryotic homologue Rad51 protein catalyzes the DNA strand
      exchange, which is a key reaction of homologous recombination. At the initial
      step of the reaction, RecA proteins form a helical filament on a single-stranded
      DNA (ssDNA). Binding of double-stranded DNA (dsDNA) to the filament triggers the
      homology search; as homology is found, the exchange of strands occurs, and the
      displaced DNA is released. These are the principal steps of genetic
      recombination; however, despite many years of extensive study of RecA activities,
      the details of the mechanism are still obscure. A high-resolution structure of
      the active nucleoprotein filament could provide information to help understand
      this process. Using a linear dichroism polarized-light spectroscopy technique, in
      combination with protein engineering (the site-specific linear dichroism method),
      we have previously studied the arrangement of RecA in complex with ssDNA. In the
      present study, we have used this approach to search for structural variations of
      RecA at the atomic level as the DNA in the complex is changed from ssDNA to
      dsDNA. The structural data of the RecA-dsDNA filament are found to be very
      similar to the data previously obtained for the RecA-ssDNA complex, indicating
      that the overall orientation and also the internal structure of RecA in the
      active filament are not markedly altered when the bound DNA changes from single-
      to double-stranded. The implications of the structural similarities as well as
      the significance of some conformational variations observed for a few amino acid
      residues that may be involved in interactions with DNA are discussed.

PMID- 16964979
TI  - Comparison between the backbone dynamics of an 11-amino acid peptide sequence in
      alpha-helical and beta-hairpin structural contexts.
AB  - To investigate the relationship between backbone motions and the structural
      environment of a peptide sequence, we have used (15)N NMR relaxation data to
      characterize the backbone motions of the "chameleon-alpha" (Chm-alpha) and
      "chameleon-beta" (Chm-beta) proteins designed previously by Minor and Kim [Minor,
      D. L., Jr., and Kim, P. S. (1996) Nature 380, 730-734]. These two proteins
      contain an identical 11-amino acid sequence (dubbed the "chameleon" peptide
      sequence) in alpha-helix and beta-hairpin conformations, respectively, within the
      B1 domain of protein G. When placed in an alpha-helical context, the chameleon
      peptide shows very limited backbone motions, but some remote regions of the
      protein are induced to undergo conformational exchange motions, apparently due to
      modification of packing interactions with the chameleon peptide. In contrast,
      within a beta-hairpin context, the chameleon peptide displays substantial motions
      on both picosecond and microsecond-to-millisecond time scales, suggesting that it
      cannot be readily accommodated within the native reverse turn structure. These
      observations are consistent with the relatively low stability of the Chm-beta
      protein and can be rationalized in terms of native turn-stabilizing interactions
      that may be disrupted in the Chm-beta protein.

PMID- 16964980
TI  - Hydrogen bonds between the alpha and beta subunits of the F1-ATPase allow
      communication between the catalytic site and the interface of the beta catch loop
      and the gamma subunit.
AB  - F(1)-ATPase mutations in Escherichia coli that changed the strength of hydrogen
      bonds between the alpha and beta subunits in a location that links the catalytic
      site to the interface between the beta catch loop and the gamma subunit were
      examined. Loss of the ability to form the hydrogen bonds involving alphaS337,
      betaD301, and alphaD335 lowered the k(cat) of ATPase and decreased its
      susceptibility to Mg(2+)-ADP-AlF(n) inhibition, while mutations that maintain or
      strengthen these bonds increased the susceptibility to Mg(2+)-ADP-AlF(n)
      inhibition and lowered the k(cat) of ATPase. These data suggest that hydrogen
      bonds connecting alphaS337 to betaD301 and betaR323 and connecting alphaD335 to
      alphaS337 are important to transition state stabilization and catalytic function
      that may result from the proper alignment of catalytic site residues betaR182 and
      alphaR376 through the VISIT sequence (alpha344-348). Mutations betaD301E,
      betaR323K, and alphaR282Q changed the rate-limiting step of the reaction as
      determined by an isokinetic plot. Hydrophobic mutations of betaR323 decreased the
      susceptibility to Mg(2+)-ADP-AlF(n)() inhibition and lowered the number of
      interactions required in the rate-limiting step yet did not affect the k(cat) of
      ATPase, suggesting that betaR323 is important to transition state formation. The
      decreased rate of ATP synthase-dependent growth and decreased level of lactate
      dependent quenching observed with alphaD335, betaD301, and alphaE283 mutations
      suggest that these residues may be important to the formation of an alternative
      set of hydrogen bonds at the interface of the alpha and beta subunits that
      permits the release of intersubunit bonds upon the binding of ATP, allowing gamma
      rotation in the escapement mechanism.

PMID- 16964981
TI  - Determinants of alpha-conotoxin BuIA selectivity on the nicotinic acetylcholine
      receptor beta subunit.
AB  - Neuronal nicotinic acetylcholine receptors (nAChRs) are pentamers composed of
      alpha and beta subunits. Different molecular compositions of these subunits
      constitute various receptor subtypes that are implicated in the pathophysiology
      and/or treatment of several disease states but are difficult to distinguish
      pharmacologically. Alpha-conotoxins are a group of small, structurally defined
      peptides that may be used to molecularly dissect the nAChR-binding site.
      Heteromeric nAChRs generally contain either a beta2 or beta4 subunit in addition
      to an alpha subunit at the ligand-binding interface. Alpha-conotoxin BuIA
      kinetically distinguishes between beta2- and beta4-containing nAChRs, with long
      off times for the latter. Mutational studies were used to assess the influence of
      residues that line the putative acetylcholine-binding pocket but differ between
      beta2 and beta4 subunits. Residues Thr/Lys59, Val/Ile111, and Phe/Gln119 of the
      respective beta2 and beta4 subunits are critical to off-rate differences. Among
      these residues, Thr59 of nAChR beta2 may interfere with effective access to the
      binding site, whereas Lys59 may facilitate this binding.

PMID- 16964982
TI  - Probing the unusual oxidation/reduction behavior of Paracoccus pantotrophus
      cytochrome cd1 nitrite reductase by replacing a switchable methionine heme iron
      ligand with histidine.
AB  - A M106H variant, where M106 is a c-type heme iron axial ligand, of cytochrome
      cd(1) nitrite reductase is an inactive protein in vivo. Expression of the
      holoprotein in Paracoccus pantotrophus required generation of nitric oxide during
      cell growth through simultaneous expression of an exogenous copper nitrite
      reductase from Alcaligenes faecalis. In the absence of the latter protein, only a
      semi-apo form of M106H cytochrome cd(1) was formed. Thus it was demonstrated that
      expression of the chromosomal nir genes for d(1) heme biosynthesis in P.
      pantotrophus is NO-dependent, probably mediated by the transcription factor NNR,
      and a route to low or zero activity mutants had been established. The value of
      such variants for mechanistic studies on cytochrome cd(1) is illustrated by the
      use of M106H to demonstrate that the d(1) heme potential can be resolved and
      measured at approximately +175 mV with the c heme shifted to -60 mV, consistent
      with its bishistidinyl coordination. The unusual highly cooperative and strongly
      hysteretic redox titration of the wild type is lost in the M106H protein. The
      same c heme midpoint potential was observed in a M106H variant of a c-domain
      construct. The difference between d(1) heme and c heme redox potentials has
      allowed preparation of a M106H protein with oxidized c heme and reduced d(1)
      heme. This one electron reduced form will reduce nitrite to nitric oxide, but the
      latter remains bound to the resulting fully oxidized enzyme.

PMID- 16964983
TI  - La(3+)-induced extracellular signal-regulated kinase (ERK) signaling via a metal
      sensing mechanism linking proliferation and apoptosis in NIH 3T3 cells.
AB  - The effects of La(3+) on the extracellular signal-regulated kinase (ERK)
      signaling were investigated to explore the mechanism by which La(3+) results in
      cell proliferation associated with apoptosis in mouse embryo fibroblast NIH 3T3
      cells. Our data showed that La(3+) ions could induce a pulse of phosphorylation
      of ERK mainly through an unknown metal-sensing mechanism, which is different from
      the Ca(2+)-sensing receptor . The putative sensor protein showed one binding site
      for La(3+) with a dissociation constant of approximately 8 nM. Inductions of c
      fos, c-myc, and cyclin D1 and phosphorylation of retinoblastoma protein (pRb)
      were observed after activation of ERK. These results are consistent with our
      previous observation that La(3+) promotes proliferation by helping the cells pass
      through the G1/S restriction point and enter S phase. This La(3+)-induced
      signaling cascade exhibited abnormally sustained c-myc induction and pRb
      phosphorylation. Furthermore, a continual increase of the p53 level was observed
      along with the signal transduction, and a significant decrease of B-cell
      lymphoma/leukemia-2 gene was observed after approximately 18 h of incubation. All
      of the results were highly correlated with the increase of S-phase population and
      apoptotic cells. Therefore, the experimental results suggested that La(3+)
      induced cell proliferation and apoptosis compatible to a p53-related mechanism in
      NIH 3T3 cells via an ERK-signaling cascade induced by a metal-sensing mechanism.

PMID- 16964984
TI  - HX-ESI-MS and optical studies of the unfolding of thioredoxin indicate
      stabilization of a partially unfolded, aggregation-competent intermediate at low
      pH.
AB  - Hydrogen exchange monitored by mass spectrometry (HX-MS), in conjunction with
      multiple optical probes, has been used to characterize the unfolding of
      thioredoxin. Equilibrium and kinetic studies have been carried out at pH 7 and 3.
      The HX-MS measurements are shown to be capable of distinguishing between native
      (N) and unfolded (U) protein molecules when both are present together, and their
      application in kinetic experiments allows the unfolding reaction to be delineated
      from the proline isomerization reaction to which it is coupled. At pH 7,
      equilibrium unfolding studies monitored by three optical probes, intrinsic
      fluorescence at 368 nm, ellipticity at 222 nm, and ellipticity at 270 nm, as well
      as by HX-MS, indicate that no intermediate is populated at pH 7, the unfolding
      reaction is slower than the proline isomerization reaction that follows it, and
      the three optical probes yield identical kinetics for unfolding, which occurs in
      a single kinetic phase. The fractional change in any of the three optical signals
      at any time of unfolding predicts the fraction of the molecules that have become
      U, as determined by HX-MS. Hence, unfolding at pH 7 appears to occur via a two
      state N <==> U mechanism. In contrast at pH 3, HX-MS as well as optical
      measurements indicate that an unfolding intermediate is stabilized and hence
      accumulates in equilibrium with N and U, at concentrations of denaturant that
      define the transition zone of the equilibrium unfolding curve. The intermediate
      has lost the near-UV signal characteristic of N and possesses fewer amide
      hydrogen sites that are stable to exchange than does N. Kinetic experiments at pH
      3, where unfolding is much faster than proline isomerization, show that more than
      one intermediate accumulates transiently during unfolding. Thus, the unfolding of
      thioredoxin occurs via an N <==> I <==> U mechanism, where I is a partially
      unfolded intermediate that is stabilized and hence populated at pH 3 but not at
      pH 7. It is shown that transient aggregation of this intermediate results in a
      deceleration of the kinetics of unfolding at high protein concentrations at pH 3
      but not at pH 7.

PMID- 16964985
TI  - Differential distortion of substrate occurs when it binds to DNA photolyase: a 2
      aminopurine study.
AB  - Cyclobutylpyrimidine dimers (CPDs) are formed between adjacent pyrimidines in DNA
      when it is exposed to ultraviolet light. CPDs can be directly repaired by DNA
      photolyase (PL) upon absorption of blue-green light. We have used the fluorescent
      adenine analogue 2-aminopurine (2Ap) to probe the local double-helical structure
      of the DNA substrate when it binds to the protein. Duplex melting temperatures
      and van't Hoff enthalpies were obtained by both UV-vis absorption and
      fluorescence spectroscopies to ascertain the effect of the probe and CPD on DNA
      stability. Steady-state fluorescence measurements of the single- and double
      stranded oligos showed that the local region around the 5'-side of the CPD lesion
      was more disrupted and destacked than the 3'-side in substrate-protein complexes.
      These results were compared with those of a protein-substrate crystal structure,
      demonstrating that the crystal structure and solution-state studies are in
      agreement with regard to the differential distortions of the target DNA at the
      active site of the protein.

PMID- 16964986
TI  - The problem of low levels of vitamin D and osteoporosis: use of combination
      therapy with alendronic acid and colecalciferol (vitamin D3).
AB  - Osteoporosis and fragility fractures are common in the elderly population and
      represent a large public health burden. Non-pharmacological recommendations for
      the management of osteoporosis include modification of lifestyle behaviours,
      increased weight-bearing exercise and consumption - through dietary or supplement
      sources - of adequate amounts of calcium and vitamin D. Although current
      guidelines include recommendations on calcium and vitamin D intake, patients
      frequently do not take sufficient amounts, even when supplements are provided
      free of charge. Vitamin D is essential for mineral metabolism, and low levels are
      associated with impaired skeletal metabolism and neuromuscular function.
      Nutritional sources of vitamin D are limited, and supplementation is usually
      necessary. A high prevalence of low vitamin D levels has been reported in a
      number of populations worldwide, including women being treated for osteoporosis
      and those with fragility fractures. At present, bisphosphonates are the most
      commonly prescribed pharmacological treatments for osteoporosis, and alendronic
      acid is the most frequently prescribed bisphosphonate. A nitrogen-containing
      bisphosphonate, alendronic acid has demonstrated anti-fracture efficacy at
      vertebral and non-vertebral skeletal sites, including the hip, in addition to
      long-term safety and efficacy. Weekly administration of alendronic acid takes
      advantage of the pharmacokinetics of the drug and osteoclast biology to optimise
      treatment, and may improve patient adherence. Combining alendronic acid 70mg and
      colecalciferol (vitamin D(3)) 2800 IU in a single, once-weekly tablet has the
      advantage of combining the proven efficacy of an established bisphosphonate,
      alendronic acid, with the amount of vitamin D currently recommended for
      osteoporosis management.

PMID- 16964990
TI  - Gerontology forum: an update on the literature.
AB  - New treatments and treatment protocols for diseases affecting the elderly are
      evolving as we strive to meet the needs of an aging society. To help you keep up
      to date with the latest advances worldwide on all aspects of drug therapy and
      patient management, this section of the journal brings you information selected
      from the rapid drug news alerting service Inpharma Weekly. Each issue contains
      easy-to-read summaries of the most important research and development news,
      clinical studies, treatment guidelines, and pharmacoeconomic news.

PMID- 16964987
TI  - Giant cell arteritis and polymyalgia rheumatica: pathophysiology and management.
AB  - Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are common and often
      concurrent diseases in Western countries in individuals aged >50 years. Clinical
      features of GCA are mainly due to involvement of the cranial arteries. PMR is
      clinically characterised by pain, aching and morning stiffness involving the
      neck, shoulder and hip girdles. Both conditions are generally associated with
      elevation of erythrocyte sedimentation rate and C-reactive protein. A temporal
      artery biopsy is the gold standard test for the diagnosis of GCA. Some diseases
      may mimic PMR or present with polymyalgic symptoms. Corticosteroids are the
      cornerstone of the management of GCA and PMR. An initial dosage of prednisone 10
      20 mg/day yields a dramatic improvement of PMR symptoms in most cases. In GCA,
      the initial prednisone dosage required is higher (40-60 mg/day). However, once
      established, visual loss, which is the most feared complication of GCA, does not
      usually improve following corticosteroid therapy. Some patients exhibit a chronic
      relapsing course and may need low doses of corticosteroids for several years.
      Alternative corticosteroid-sparing therapies and some therapeutic agents aimed at
      restoring balanced bone cell activity in patients taking corticosteroids are
      potentially useful in the management of GCA and PMR.

PMID- 16964989
TI  - Intravenous esmolol is well tolerated in elderly patients with heart failure in
      the early phase of non-ST elevation myocardial infarction.
AB  - AIM: To investigate the haemodynamic response to and clinical safety and
      tolerability of intravenous esmolol (Brevibloc), Baxter Healthcare Corporation,
      Deerfield, Illinois, USA) in elderly and younger patients with acute non-ST
      elevation myocardial infarction (NSTEMI) and heart failure. PATIENTS AND METHODS:
      We studied 24 consecutive patients, 12 of them elderly (> or =75 years old) and
      12 younger (32-74 years old), with NSTEMI and symptoms of heart failure on
      presentation. After stabilisation of the patient's condition with standard
      therapy, intravenous esmolol was administered. An infusion rate of 0.05 mg/kg/min
      for 30 minutes was instituted and, if no adverse effects developed, this was
      increased to 0.20 mg/kg/min. All haemodynamic parameters were measured before and
      at the end of each administration using a Swan-Ganz catheter. RESULTS: Only one
      patient in the elderly subgroup did not tolerate the augmented infusion rate
      (because of severe bradycardia) and so had to return to the initial lower
      infusion rate. The cardiac index (mean +/- SD) was 2.4 +/- 0.9 L/min/m(2) at
      baseline and decreased to 1.9 +/- 0.4 L/min/m(2) (p < 0.05 vs baseline) at the
      end of the administration of the second dose of esmolol in the elderly patients
      and 2.6 +/- 0.5 L/min/m(2) and 2.2 +/- 0.5 L/min/m(2) (p < 0.05 vs baseline),
      respectively, in the younger patients. Mean pulmonary wedge pressure was 17 +/-
      6mm Hg at baseline and increased to 19 +/- 4mm Hg (p < 0.05 vs baseline) at the
      end of the second dose of esmolol in the elderly patients and 16 +/- 10mm Hg and
      18 +/- 10mm Hg (p < 0.05 vs baseline), respectively, in the younger patients. The
      response of both age groups to esmolol was the same for all of the parameters
      examined. CONCLUSION: Intravenous esmolol was safe and well tolerated in the
      early phase of NSTEMI in patients presenting with symptoms of heart failure and
      ongoing ischaemia, regardless of their age.

PMID- 16964988
TI  - Management of venous thromboembolism in the elderly.
AB  - In this review the authors discuss the use of oral and parenteral anticoagulants
      for the prevention and treatment of venous thromboembolism (VTE) in the elderly.
      The use of anticoagulant agents in VTE prophylaxis and treatment in the elderly
      is complicated by an increase with age in the presence of multiple risk factors
      and co-morbidities that may increase the risk of both VTE and bleeding. Age
      itself is identified as an independent risk factor for thromboembolism. VTE is
      underdiagnosed in the elderly population, and routine prophylaxis frequently
      falls short of the levels required according to level of risk. Although
      appropriate anticoagulation of at-risk patients offers a means of reducing the
      significant VTE burden in this population, concerns have been raised over the use
      of anticoagulants in a patient group in whom multiple risk factors are common.
      Bleeding in the elderly can be exacerbated by reduced renal clearance and
      hypersensitivity to oral anticoagulants that may lead to over-anticoagulation.
      Although bleeding due to anticoagulant therapy is a serious issue in the elderly,
      it is often overemphasized, given the therapeutic value otherwise observed in
      treating this patient group. Warfarin is still used in VTE prophylaxis after
      orthopaedic surgery and for long-term VTE treatment. Unfractionated and low
      molecular-weight heparins (LMWHs) have been shown to be safe and effective in the
      prophylaxis of VTE, and are now being shown to be as effective as warfarin in the
      initial and long-term treatment of VTE. LMWHs confer the advantage over
      unfractionated heparin of subcutaneous once-daily administration with no
      requirement for laboratory monitoring of their anticoagulant effect, which allows
      for the convenience of outpatient therapy. New anticoagulants that may be of
      potential benefit in this patient population include fondaparinux sodium, but
      clinical experience of this drug in the elderly remains limited.

PMID- 16964991
TI  - Quasiclassical trajectory calculations of the reaction C+C2H2-->l-C3H, c-C3H+H,
      C3+H2 using full-dimensional triplet and singlet potential energy surfaces.
AB  - Full-dimensional, density functional theory (B3LYP/6-311g(d,p))-based potential
      energy surfaces (PESs) are reported and used in quasi-classical calculations of
      the reaction of C with C(2)H(2). For the triplet case, the PES spans the region
      of the reactants, the complex region (with numerous minima and saddle points) and
      the products, linear(l)-C(3)H+H, cyclic(c)-C(3)H+H and c-(3)C(3)+H(2). For the
      singlet case, the PES describes the complex region and products l-C(3)H+H, c
      C(3)H+H and l-(1)C(3)+H(2). The PESs are invariant under permutation of like
      nuclei and are fit to tens of thousands of electronic energies. Energies and
      harmonic frequencies of the PESs agree well the DFT ones for all stationary
      points and for the reactant and the products. Dynamics calculations on the
      triplet PES find both l-C(3)H and c-C(3)H products, with l-C(3)H being dominant
      at the energies considered. Limited unimolecular reaction dynamics on the singlet
      PES find both products in comparable amounts as well as the C(3)+H(2) product.

PMID- 16964992
TI  - One-dimensional arrays of nanoshell dimers for single molecule spectroscopy via
      surface-enhanced Raman scattering.
AB  - The optical properties of one-dimensional arrays of metal nanoshell dimers are
      studied systematically using the T-matrix method based on Mie theory, within the
      context of surface enhanced Raman scattering (SERS). It is shown that the local
      electromagnetic enhancement can be as high as approximately 4.5 x 10(13) for
      nanoshell dimer arrays with optimal geometry, and sensitive tunability in the
      resonant frequency can be gained by varying the geometrical parameters, making
      such structures appealing templates for SERS measurements with single molecule
      sensitivity. The extraordinarily high enhancement is attributed to a collective
      photonic effect constructively superposed onto the intrinsic enhancement
      associated with an isolated nanoshell dimer.

PMID- 16964993
TI  - Capillary electrophoresis of ultrasmall carboxylate functionalized silicon
      nanoparticles.
AB  - Capillary electrophoresis is used to separate ultrasmall ( approximately 1 nm)
      carboxylate functionalized Si nanoparticles (Si-np-COO(-)) prepared via
      hydrosilylation with an omega-ester 1-alkene. The electropherograms show a
      monodisperse Si core size with one or two carboxylate groups added to the
      surface. On-column detection of their laser-induced fluorescence demonstrates
      that the individual Si-np-COO(-) have narrow emissions (full width at half
      maximum = 30-40 nm) with a nearly symmetric lineshape. Preparative scale
      electrophoresis should be a viable route for purification of the Si-np-COO(-) for
      further study and future applications.

PMID- 16964994
TI  - Effective local potentials for orbital-dependent density functionals.
AB  - Practicality of the Kohn-Sham density functional scheme for orbital-dependent
      functionals hinges on the availability of an efficient procedure for constructing
      local exchange-correlation potentials in finite basis sets. We have shown
      recently that the optimized effective potential (OEP) method, commonly used for
      this purpose, is not free from difficulties. Here we propose a robust alternative
      to OEPs, termed effective local potentials (ELPs), based on minimizing the
      variance of the difference between a given nonlocal potential and its desired
      local counterpart. The ELP method is applied to the exact-exchange-only problem
      and shown to be promising for overcoming troubles with OEPs.

PMID- 16964995
TI  - Structure and stability of the Al14 halides Al14In - (n=1-11): can we regard the
      Al14 core as an alkaline earthlike superatom?
AB  - We have studied the structures and stabilities of Al(14)I(n) (-) (n=1-11)
      clusters at the density functional level of theory. The experimentally observed
      Al(14)I(n) (-) (n=3, 5, 7, 9, and 11) [Bergeron et al., Science 307, 231 (2005)]
      are found to be stable both kinetically and thermodynamically. Al(14)I(3) (-),
      not Al(14)I(-), is the first member of the Al(14)I(n) (-) series in the mass
      spectrometric experiment, which is ascribable to the low kinetic stability of the
      Al(14)I(-) cluster. The Al(14) core in Al(14)I(3) (-) is close to neutral Al(14),
      both electronically and structurally. Population analysis shows that charge
      transfer occurs from the Al cluster to the I atoms, where the populations for
      Al(14) vary from -0.70(Al(14)I(-)) to +0.96(Al(14)I(11) (-)). The Al(14)I(5) (-)
      and Al(14)I(7) (-) clusters have the structure of Al(14)I(3) (-) as a core
      framework, but, for n=9 and 11, we found many more stable isomers than the
      isomers having the Al(14)I(3) (-) core. In particular, the shape of Al(14) in the
      Al(14)I(11) (-) cluster is a hexagonal wheel-shaped form, which was observed in
      the x-ray experiment for the metalloid complex
      [Al(14){N(SiMe(3))(2)}(6)I(6)Li(OEt(2))(2)](-)[Li(OEt(2))(4)](+)toluene [Kohnlein
      et al., Angew. Chem., Int. Ed. 39, 799 (2000)]. We have demonstrated that a
      simple jellium model cannot describe the structure and stability of the iodine
      doped aluminum clusters, although it is successful for describing those of
      aluminum clusters. The electronic and geometric changes of the Al(14) (-) cluster
      due to the presence of iodines are very similar to the case of a magic cluster
      Al(13) (-). It can be concluded from our electronic and structural analysis that
      one cannot regard the Al(14) core as an alkaline earthlike superatom in the
      Al(14) iodide clusters.

PMID- 16964996
TI  - Self-consistent embedding theory for locally correlated configuration interaction
      wave functions in condensed matter.
AB  - We present new developments on a density-based embedding strategy for the
      electronic structure of localized feature in periodic, metallic systems [see T.
      Kluner et al., J. Chem. Phys. 116, 42 (2002), and references therein]. The total
      system is decomposed into an embedded cluster and a background, where the
      background density is regarded as fixed. Its effect on the embedded cluster is
      modeled as a one-electron potential derived from density functional theory. We
      first discuss details on the evaluation of the various contributions to the
      embedding potential and provide a strategy to incorporate the use of ultrasoft
      pseudopotentials in a consistent fashion. The embedding potential is obtained
      self-consistently with respect to both the total and embedded cluster densities
      in the embedding region, within the framework of a frozen background density. A
      strategy for accomplishing this self-consistency in a numerically stable manner
      is presented. Finally, we demonstrate how dynamical correlation effects can be
      treated within this embedding framework via the multireference singles and
      doubles configuration interaction method. Two applications of the embedding
      theory are presented. The first example considers a Cu dimer embedded in the
      (111) surface of Cu, where we explore the effects of different models for the
      kinetic energy potential. We find that the embedded Cu density is reasonably well
      described using simple models for the kinetic energy. The second, more
      challenging example involves the adsorption of Co on the (111) surface of Cu,
      which has been probed experimentally with scanning tunneling microscopy [H. C.
      Manoharan et al., Nature (London) 403, 512 (2000)]. In contrast to Kohn-Sham
      density functional theory, our embedding approach predicts the correct spin
      compensated ground state.

PMID- 16964997
TI  - R-leaping: accelerating the stochastic simulation algorithm by reaction leaps.
AB  - A novel algorithm is proposed for the acceleration of the exact stochastic
      simulation algorithm by a predefined number of reaction firings (R-leaping) that
      may occur across several reaction channels. In the present approach, the numbers
      of reaction firings are correlated binomial distributions and the sampling
      procedure is independent of any permutation of the reaction channels. This
      enables the algorithm to efficiently handle large systems with disparate rates,
      providing substantial computational savings in certain cases. Several mechanisms
      for controlling the accuracy and the appearance of negative species are
      described. The advantages and drawbacks of R-leaping are assessed by simulations
      on a number of benchmark problems and the results are discussed in comparison
      with established methods.

PMID- 16964998
TI  - A dipole interaction model for magnetochiral birefringence.
AB  - We have developed a classical model to investigate the magnetochiral
      birefringence of an isotropic chiral medium submitted to a longitudinal magnetic
      field. This model, which is an extension of the atom dipole interaction model,
      yields direct calculations from the polarizabilities and positions of the atoms
      of the considered molecules. The numerical values obtained for the magnetochiral
      birefringence, as well as for the optical activity and Faraday rotation, are
      supported by the previously published experimental results on limonene, proline,
      and tartaric acid.

PMID- 16964999
TI  - On the degeneracy of atomic states within exact-exchange (spin-) density
      functional theory.
AB  - The problem of degenerate ground states of open-shell atoms is investigated in
      spin-restricted and spin-unrestricted density functional theories using the exact
      exchange energy functional. For the spin-unrestricted case, spurious energy
      splittings of the order of 2-3 kcal/mol are found for atoms of the second and
      third periods which are larger than the splittings obtained from recently
      proposed approximate exchange functionals depending explicitly on the current
      density. In remarkable contrast, for spin-restricted calculations the degeneracy
      of different atomic ground states is recovered to within less than 0.6 kcal/mol.

PMID- 16965000
TI  - Efficient implementation of the fast multipole method.
AB  - A number of computational techniques are described that reduce the effort related
      to the continuous fast multipole method, used for the evaluation of Coulomb
      matrix elements as needed in Hartree-Fock and density functional theories. A new
      extent definition for Gaussian charge distributions is proposed, as well as a new
      way of dividing distributions into branches. Also, a new approach for estimating
      the error caused by truncation of multipole expansions is presented. It is found
      that the use of dynamically truncated multipole expansions gives a speedup of a
      factor of 10 in the work required for multipole interactions, compared to the
      case when all interactions are computed using a fixed multipole expansion order.
      Results of benchmark calculations on three-dimensional systems are reported,
      demonstrating the usefulness of our present implementation of the fast multipole
      method.

PMID- 16965001
TI  - Accelerating molecular simulations by reversible mapping between local minima.
AB  - A new framework is presented for performing Monte Carlo simulations of condensed
      matter based on a recently developed bijective mapping between local energy
      minima. The framework is used to implement a range of new multiparticle Monte
      Carlo moves, which are investigated by simulating atomic Lennard-Jones fluids in
      the canonical and grand canonical ensembles. Important aspects of the simulation
      protocol and their effect on performance are analyzed in detail. Using the
      mapping accelerates the simulations by many orders of magnitude when compared to
      the equivalent moves without the mapping, and leads to particularly efficient
      configurational sampling at low temperatures and high densities. The method
      appears to be suitable for adapting to quantitative simulations of more complex
      molecular systems over long effective time scales.

PMID- 16965002
TI  - A size extensive energy functional derived from a double configuration
      interaction approach: the role of N representability conditions.
AB  - Starting from a configuration interaction (CI) approach including only doubly
      excited configurations, the corresponding energy functional is modified by
      introduction of a topological factor in the normalization condition of the CI
      coefficients in such a way that it gets inherently size extensive. Constraints
      imposed by N representability conditions on the modified functional are discussed
      and lead to a specific choice of the topological factor. The basic variable in
      the modified energy functional is the second-order reduced density matrix
      parametrized in terms of CI-like coefficients. Test calculations for a variety of
      small molecules show that the numerical results obtained with the new functional
      are in very good agreement with those obtained from coupled cluster singles
      doubles calculations.

PMID- 16965003
TI  - A random-sampling high dimensional model representation neural network for
      building potential energy surfaces.
AB  - We combine the high dimensional model representation (HDMR) idea of Rabitz and co
      workers [J. Phys. Chem. 110, 2474 (2006)] with neural network (NN) fits to obtain
      an effective means of building multidimensional potentials. We verify that it is
      possible to determine an accurate many-dimensional potential by doing low
      dimensional fits. The final potential is a sum of terms each of which depends on
      a subset of the coordinates. This form facilitates quantum dynamics calculations.
      We use NNs to represent HDMR component functions that minimize error mode term by
      mode term. This NN procedure makes it possible to construct high-order component
      functions which in turn enable us to determine a good potential. It is shown that
      the number of available potential points determines the order of the HDMR which
      should be used.

PMID- 16965004
TI  - Illustration of transition path theory on a collection of simple examples.
AB  - Transition path theory (TPT) has been recently introduced as a theoretical
      framework to describe the reaction pathways of rare events between long lived
      states in complex systems. TPT gives detailed statistical information about the
      reactive trajectories involved in these rare events, which are beyond the realm
      of transition state theory or transition path sampling. In this paper the TPT
      approach is outlined, its distinction from other approaches is discussed, and,
      most importantly, the main insights and objects provided by TPT are illustrated
      in detail via a series of low dimensional test problems.

PMID- 16965005
TI  - Retarded boson-fermion interaction in atomic systems.
AB  - The retarded interaction between an electron and a spin-0 nucleus is derived from
      electrodynamical perturbation theory. The contribution of retardation at order
      v(2)c(2) mimics the Breit interaction [Phys. Rev. 34, 553 (1929); 36, 388 (1930);
      39, 616 (1932)] with the Dirac matrix alpha(2) being replaced by p(2)m(2)c where
      p(2) is the linear momentum operator for the nucleus. An effective one-electron
      retardation operator is obtained in relative coordinates, and this can be used
      through all orders in perturbation theory without any problem of infinite
      degeneracy. A few steps of unitary transformation lead to the nonrelativistic
      limit. The leading terms in retardation corrections to energy are of order
      (m(e)m(n))alpha(2)Z(4)(alpha(2)m(e)c(2)). The implications for atomic systems are
      discussed.

PMID- 16965006
TI  - Photodissociation dynamics of the NO dimer. I. Theoretical overview of the
      ultraviolet singlet excited states.
AB  - Molecular orbital theory and calculations are used to describe the ultraviolet
      singlet excited states of NO dimer. Qualitatively, we derive and catalog the
      dimer states by correlating them with monomer states, and provide illustrative
      complete active space self-consistent field calculations. Quantitatively, we
      provide computational estimates of vertical transition energies and absorption
      intensities with multireference configuration interaction and equations-of-motion
      coupled-cluster methods, and examine an important avoided crossing between a
      Rydberg and a valence state along the intermonomer and intramonomer stretching
      coordinates. The calculations are challenging, due to the high density of
      electronic states of various types (valence and Rydberg, excimer and charge
      transfer) in the 6-8 eV region, and the multiconfigurational nature of the ground
      state. We have identified a bright charge-transfer (charge-resonance) state as
      responsible for the broadband seen in UV absorption experiments. We also use our
      results to facilitate the interpretation of UV photodissociation experiments,
      including the time-resolved 6 eV photodissociation experiments to be presented in
      the next two papers of this series.

PMID- 16965007
TI  - Ab initio determination of the ionization potentials of DNA and RNA nucleobases.
AB  - Quantum chemical high level ab initio coupled-cluster and multiconfigurational
      perturbation methods have been used to compute vertical and adiabatic ionization
      potentials of the five canonical DNA and RNA nucleobases: uracil, thymine,
      cytosine, adenine, and guanine. Several states of their cations have been also
      calculated. The present results represent a systematic compendium of these
      magnitudes, establishing theoretical reference values at a level not reported
      before, calibrating computational strategies, and guiding the assignment of the
      features in the experimental photoelectron spectra.

PMID- 16965008
TI  - Darwin and mass-velocity relativistic corrections in non-Born-Oppenheimer
      variational calculations.
AB  - The Pauli approach to account for the mass-velocity and Darwin relativistic
      corrections has been applied to the formalism for quantum mechanical molecular
      calculations that does not assume the Born-Oppenheimer (BO) approximation
      regarding separability of the electronic and nuclear motions in molecular
      systems. The corrections are determined using the first order perturbation theory
      and are derived for the non-BO wave function of a diatomic system expressed in
      terms of explicitly correlated Gaussian functions with premultipliers in the form
      of even powers of the internuclear distance. As a numerical example we used
      calculations of the transition energies for pure vibrational states of the HD(+)
      ion.

PMID- 16965010
TI  - Statistical thermodynamics of bond torsional modes: tests of separable, almost
      separable, and improved Pitzer-Gwinn approximations.
AB  - Practical approximation schemes for calculating partition functions of torsional
      modes are tested against accurate quantum mechanical results for H(2)O(2) and six
      isotopically substituted hydrogen peroxides. The schemes are classified on the
      basis of the type and amount of information that is required. First, approximate
      one-dimensional hindered-rotator partition functions are benchmarked against
      exact one-dimensional torsion results obtained by eigenvalue summation. The
      approximate one-dimensional methods tested in this stage include schemes that
      only require the equilibrium geometries and frequencies, schemes that also
      require the barrier heights of internal rotation, and schemes that require the
      whole one-dimensional torsional potential. Then, three classes of approximate
      full-dimensional vibrational-rotational partition functions are calculated and
      are compared with the accurate full-dimensional path integral partition
      functions. These three classes are (1) separable approximations combining
      harmonic oscillator-rigid rotator models with the one-dimensional torsion
      schemes, (2) almost-separable approximations in which the nonseparable zero-point
      energy is used to correct the separable approximations, and (3) improved
      nonseparable Pitzer-Gwinn-type methods in which approaches of type 1 are used as
      reference methods in the Pitzer-Gwinn approach. The effectiveness of these
      methods for the calculation of isotope effects is also studied. Based on the
      results of these studies, the best schemes of each type are recommended for
      further use on systems where a corresponding amount of information is available.

PMID- 16965009
TI  - High resolution dissociative electron attachment to gas phase adenine.
AB  - The dissociative electron attachment to the gas phase nucleobase adenine is
      studied using two different experiments. A double focusing sector field mass
      spectrometer is utilized for measurements requiring high mass resolution, high
      sensitivity, and relative ion yields for all the fragment anions and a
      hemispherical electron monochromator instrument for high electron energy
      resolution. The negative ion mass spectra are discussed at two different electron
      energies of 2 and 6 eV. In contrast to previous gas phase studies a number of new
      negative ions are discovered in the mass spectra. The ion efficiency curves for
      the negative ions of adenine are measured for the electron energy range from
      about 0 to 15 eV with an electron energy resolution of about 100 meV. The total
      anion yield derived via the summation of all measured fragment anions is compared
      with the total cross section for negative ion formation measured recently without
      mass spectrometry. For adenine the shape of the two cross section curves agrees
      well, taking into account the different electron energy resolutions; however, for
      thymine some peculiar differences are observed.

PMID- 16965011
TI  - The photoelectron spectrum of elusive cyclic-N3 and characterization of the
      potential energy surface and vibrational states of the ion.
AB  - A potential energy surface is constructed for the ground X (1)A(1) electronic
      state of cyclic-N(3) (+) based on three-dimensional spline interpolation of ab
      initio points. The vibrational states of this molecular ion are calculated in the
      range up to 14 500 cm(-1) using hyperspherical coordinates and the coupled
      channel (sector-adiabatic) approach. All the vibrational states are analyzed and
      assigned. The Franck-Condon overlaps of these states with the vibrational states
      of the neutral are calculated to predict the photoelectron spectrum of cyclic
      N(3). Peak intensities are governed by the nodal structure of the vibrational
      wave functions and reflect the large geometric phase effect predicted for cyclic
      N(3). Experimental validation may shed light on the existence of this elusive
      molecule and confirm the magnitude of the geometric phase effect.

PMID- 16965012
TI  - Quantum dynamics study on multichannel dissociation and isomerization reactions
      of formaldehyde.
AB  - We study quantum dynamics of the multichannel reactions of H(2)CO including the
      molecular and radical dissociation channels as well as the isomerization ones,
      H(2)CO-->trans-HCOH and trans-HCOH-->cis-HCOH. For this purpose, the previously
      developed potential energy function [T. Yonehara and S. Kato, J. Chem. Phys. 117,
      11131 (2002)] is refined to give accurate transition state energies and to
      describe the radical dissociation channel. The cumulative reaction probabilities
      for the molecular dissociation and two isomerization channels are calculated by
      using the full Watson Hamiltonian. We also carry out wave packet dynamics
      calculations starting from the transition state region for the molecular
      dissociation. A contracted basis set for the angular coordinates is constructed
      to reduce the size of dynamics calculations. The intramolecular vibrational
      relaxation dynamics is found to be fast and almost complete within 300 fs. Using
      the energy filtered wave functions, the time propagation of HCOH population is
      obtained in the energy range from 81 to 94 kcal/mol. The branching ratio of the
      radical product is estimated by calculating the time dependent reactive fluxes to
      the molecular and radical dissociation products.

PMID- 16965013
TI  - State-resolved thermalization of singlet and mixed singlet-triplet states of CH2.
AB  - The role of mixed states in the collision-induced thermalization, intersystem
      crossing, and reactive loss of CH(2) (~a (1)A1) has been monitored using Doppler
      resolved transient frequency modulation absorption spectroscopy. Singlet CH(2) is
      produced in a hot initial distribution of translation and rotational energy
      states in the 308 nm photodissociation of ketene in a large excess of argon.
      Collisions with Ar and ketene cool the translational and rotational degrees of
      freedom, while depleting the total singlet CH(2) population through reaction and
      intersystem crossing. Direct monitoring of the time-dependent populations of
      rotational levels containing mixed singlet and triplet character reveals a rapid
      interconversion between the two components, but no discernable difference between
      the kinetics of the pure singlet and mixed states at longer times.

PMID- 16965014
TI  - Mobility of O+ in He and interaction potential of HeO+.
AB  - New experimental measurements are reported for the mobility of O(+) ions in He
      gas at 300 K. The accuracy of these new values is estimated as +/-2.5%, which
      allows them to serve as a stringent test of a new ab initio potential that we
      have calculated using the RCCSD(T) method. We employed the aug-cc-pV5Z basis set
      with counterpoise corrections and took spin-orbit coupling into account. The
      present experimental values lie below the calculated ones, but the difference
      becomes statistically significant only at moderate and high values of the ratio
      of the electric field strength to the gas number density; even there they are
      only marginally significant.

PMID- 16965015
TI  - The electronic spectrum of jet-cooled copper hydrosulfide (CuSH).
AB  - The electronic spectrum of copper hydrosulfide (CuSH) has been observed for the
      first time. CuSH and CuSD were produced in a pulsed discharge jet by the reaction
      of sputtered copper atoms with H(2)S or D(2)S. Strong laser-induced fluorescence
      bands observed in the 515-470 nm region were assigned as the ~A (1)A"-X (1)A'
      band system based on detailed rotational analysis and the correspondence with the
      predictions of our CCSD(T)6-311++G(3df,3pd) ab initio calculations. The laser
      induced fluorescence and single vibronic level emission spectra consist primarily
      of a short progression in nu(3), the Cu-S stretching mode, indicative of only
      modest structural changes on electronic excitation. The rotational constants of
      four isotopomers of CuSH were used to determine effective zero-point structures
      in the combining states as r"(CuS)=2.0916(3) A, r"(SH)=1.364(3) A, theta"=93.5(3)
      degrees , r'(CuS)=2.172(3) A, r'(SH)=1.408(23) A, and theta'=93.5(24) degrees . A
      comparison of the ground state structures of the known metal hydrosulfides shows
      that they can be considered to be metal-substituted hydrogen sulfides. The
      electronic spectra and molecular structures of CuOH and CuSH are compared and
      contrasted.

PMID- 16965016
TI  - Vibrational structures of methylamine isotopomers in the predissociative ~A
      states: CH3NHD, CD3NH2, CD3NHD, and CD3ND2.
AB  - Mass-resolved two-photon (1+1) resonance-enhanced multiphoton ionization spectra
      of the ~A-X transitions of various methylamine isotopomers (CH(3)NHD, CD(3)NH(2),
      CD(3)NHD, and CD(3)ND(2)) cooled in the supersonic jet expansion have been
      measured and analyzed. The band analysis using the Hamiltonian for the internal
      and overall rotational motions provides the accurate vibrational band positions,
      allowing for unambiguous assignments for all observed vibrational bands of
      methylamine isotopomers in the ~A states. Amino wagging (nu(9)) and methyl
      rocking (nu(7)) modes are found to be Franck-Condon active, and associated
      anharmonicity constants are precisely determined to give the detailed shape of
      the potential energy surface in the vicinity of the minimum electronic molecular
      structure. The barrier height for the nearly free internal rotation about the C-N
      bond in the ~A state is calculated to be strongly dependent on the excitation of
      the other higher-frequency vibrational modes, and it is found that the trend is
      consistent with the experiment. Experimentally measured spectroscopic constants
      are compared with ab initio calculations, confirming all vibronic assignments.
      Experimental and theoretical results on all possible HD isotopomers of
      methylamine in this work, with the earlier report on CH(3)NH(2) and CH(3)ND(2)
      Baek et al., [J. Chem. Phys. 118, 11026 (2003)], provide the complete
      spectroscopic characterization of the A state of methylamine.

PMID- 16965017
TI  - Nonadiabatic effects in the photoelectron spectrum of the pyrazolide-d3 anion:
      three-state interactions in the pyrazolyl-d3 radical.
AB  - The 351.1 nm photoelectron spectrum of the 1-pyrazolide-d(3) anion has been
      measured. The photoelectron angular distributions indicate the presence of nearly
      degenerate electronic states of the 1-pyrazolyl-d(3) radical. Equation-of-motion
      ionization potential coupled-cluster singles and doubles (EOMIP-CCSD)
      calculations have been performed to study the low-lying electronic states. The
      calculations strongly suggest that three electronic states, energetically close
      to each other, are accessed in the photodetachment process. Strong interactions
      of the pseudo-Jahn-Teller type in each pair of the three states are evident in
      the calculations for the radical at the anion geometry. Model diabatic potentials
      of the three states have been constructed around the anion geometry in terms of
      the anion reduced normal coordinates up to the second order. An analytic method
      to parametrize the quadratic vibronic coupling (QVC) model potentials has been
      introduced. Parameters of the QVC model potentials have been determined from the
      EOMIP-CCSD and CCSD(T) calculations. Simulations of the 1-pyrazolide-d(3)
      spectrum have been performed with the model Hamiltonian, treating all vibronic
      interactions amongst the three states simultaneously. The simulation reproduces
      the fine structure of the observed spectrum very well, revealing complicated
      nonadiabatic effects in the low-lying states of the radical. The ground state of
      the 1-pyrazolyl-d(3) radical is (2)A(2) and the electron affinity is 2.935+/
      0.006 eV. The first excited state is (2)B(1) with a term energy of 32+/-1 meV.
      While the high-symmetry (C(2v)) stationary points of the X (2)A(2) and A (2)B(1)
      states are minima, that of the state is a saddle point as a result of the pseudo
      Jahn-Teller interactions with the other two states. The topology of the adiabatic
      potential energy surfaces is discussed.

PMID- 16965018
TI  - A reaction surface Hamiltonian study of malonaldehyde.
AB  - We report calculations using a reaction surface Hamiltonian for which the
      vibrations of a molecule are represented by 3N-8 normal coordinates, Q, and two
      large amplitude motions, s(1) and s(2). The exact form of the kinetic energy
      operator is derived in these coordinates. The potential surface is first
      represented as a quadratic in Q, the coefficients of which depend upon the values
      of s(1),s(2) and then extended to include up to Q(6) diagonal anharmonic terms.
      The vibrational energy levels are evaluated by solving the variational secular
      equations, using a basis of products of Hermite polynomials and appropriate
      functions of s(1),s(2). Our selected example is malonaldehyde (N=9) and we choose
      as surface parameters two OH distances of the migrating H in the internal
      hydrogen transfer. The reaction surface Hamiltonian is ideally suited to the
      study of the kind of tunneling dynamics present in malonaldehyde. Our results are
      in good agreement with previous calculations of the zero point tunneling
      splitting and in general agreement with observed data. Interpretation of our two
      dimensional reaction surface states suggests that the OH stretching fundamental
      is incorrectly assigned in the infrared spectrum. This mode appears at a much
      lower frequency in our calculations due to substantial transition state
      character.

PMID- 16965019
TI  - An ab initio study of the low-lying electronic states of S3.
AB  - Accurate calculations of the low-lying singlet and triplet electronic states of
      thiozone, S(3), have been carried out using large multireference configuration
      interaction wave functions. Cuts of the full potential energy surfaces along the
      stretching and bending coordinates have been presented, together with the
      vertical excitation spectra. The strong experimentally observed absorption around
      395 nm is assigned to the 1 (1)B(2) state, which correlates to ground state
      products. Absorption at wavelengths shorter than 260 nm is predicted to lead to
      singlet excited state products, S(2) (a (1)Delta(g))+S((1)D). The spectroscopic
      properties of the X (3)Sigma(g) (-), a (1)Delta(g), and b (1)Sigma(g) (+)
      electronic states of the S(2) radical have also been accurately characterized in
      this work. The investigations of the low-lying electronic states were accompanied
      by accurate ground state coupled cluster calculations of the thermochemistry of
      both S(2) and S(3) using large correlation consistent basis sets with corrections
      for core-valence correlation, scalar relativity, and atomic spin-orbit effects.
      Resulting values for D(0)(S(2)+S) and SigmaD(0) for S(3) are predicted to be 61.3
      and 162.7 kcal/mol, respectively, with conservative uncertainties of +/-1
      kcal/mol. Analogous calculations predict the C(2v)-D(3h) (open-cyclic)
      isomerization energy of S(3) to be 4.4+/-0.5 kcal/mol.

PMID- 16965020
TI  - Rydberg states of small NaAr(n)* clusters.
AB  - The 4s and 5s Rydberg excited states of NaAr(n)* clusters are investigated using
      a pseudopotential quantum-classical method. While NaAr(n) clusters in their
      ground state are known to be weakly bound van der Waals complexes with Na lying
      at the surface of the argon cluster, isomers in 4s or 5s electronically excited
      states of small NaAr(n)* clusters (n< or =10) are found to be stable versus
      dissociation. The relationship between electronic excitation and cluster geometry
      is analyzed as a function of cluster size. For both 4s and 5s states, the stable
      exciplex isomers essentially appear as sodium-centered structures with similar
      topologies, converging towards those of the related NaAr(n)+ positive ions when
      the excitation level is increased. This is consistent with a Rydberg-type picture
      for the electronically excited cluster, described by a central sodium ion
      solvated by an argon shell, and an outer diffuse electron orbiting around this
      NaAr(n)+ cluster core.

PMID- 16965021
TI  - Steric effect in the energy transfer reaction of Ar(3P2)+N2.
AB  - Steric effect for N2(C,3Piu) formation in the energy transfer reaction of
      Ar(3P2)+N2 was directly measured by using an oriented Ar(3P2,MJ=2) beam at a
      collision energy of 0.06 eV. The N2(C,3Piu) chemiluminescence intensity was
      measured as a function of the magnetic orientation field direction in the
      collision frame. A significant alignment effect on the energy transfer
      probability was observed. The relative reactivity for each magnetic substate in
      the collision frame sigma|MJ'|was determined to be
      sigma|2|:sigma|1|:sigma(0)=0.50:0.60:1.00. It is suggested that the observed
      steric effect is primarily due to the favorable configuration of the 3p orbital
      for the efficient overlap with the 2sigma(u) molecular orbital of N(2).

PMID- 16965022
TI  - Do single-electron lithium bonds exist? Prediction and characterization of the
      H3C...Li-Y (Y=H, F, OH, CN, NC, and CCH) complexes.
AB  - A new kind of single-electron lithium bonding complexes H(3)C...LiY (Y=H, F, OH,
      CN, NC, and CCH) was predicted and characterized in the present paper. Their
      geometries (C(3v)) with all real harmonic vibrational frequencies were obtained
      at the MP2/aug-cc-pVTZ level. For each H(3)C...LiY complex, single-electron Li
      bond is formed between the unpaired electron of CH(3) radical and positively
      charged Li atom of LiY molecule. Due to the formation of the single-electron Li
      bond, the C-H bonds of the CH(3) radical bend opposite to the LiY molecule and
      the Li-Y bond elongates. Abnormally, the three H(3)C...LiY (Y=CN, NC, and CCH)
      complexes exhibit blueshifted Li-Y stretching frequencies along with the
      elongated Li-Y bonds. Natural bond orbital analyses suggest ca. 0.02 electron
      transfer from the methyl radical (CH(3)) to the LiY moiety. In the single
      occupied molecular orbitals of the H(3)C...LiY complexes, it is also seen that
      the electron could of the CH(3) radical approaches the Li atom. The single
      electron Li bond energies are 5.20-6.94 kcal/mol for the H(3)C...LiY complexes at
      the CCSD(T)aug-cc-pVDZ+BF (bond functions) level with counterpoise procedure. By
      comparisons with some related systems, it is concluded that the single-electron
      Li bonds are stronger than single-electron H bonds, and weaker than conventional
      Li bonds and pi-Li bonds.

PMID- 16965023
TI  - Modeling vibrational dephasing and energy relaxation of intramolecular anharmonic
      modes for multidimensional infrared spectroscopies.
AB  - Starting from a system-bath Hamiltonian in a molecular coordinate representation,
      we examine an applicability of a stochastic multilevel model for vibrational
      dephasing and energy relaxation in multidimensional infrared spectroscopy. We
      consider an intramolecular anharmonic mode nonlinearly coupled to a colored noise
      bath at finite temperature. The system-bath interaction is assumed linear plus
      square in the system coordinate, but linear in the bath coordinates. The square
      linear system-bath interaction leads to dephasing due to the frequency
      fluctuation of system vibration, while the linear-linear interaction contributes
      to energy relaxation and a part of dephasing arises from anharmonicity. To
      clarify the role and origin of vibrational dephasing and energy relaxation in the
      stochastic model, the system part is then transformed into an energy eigenstate
      representation without using the rotating wave approximation. Two-dimensional
      (2D) infrared spectra are then calculated by solving a low-temperature corrected
      quantum Fokker-Planck (LTC-QFP) equation for a colored noise bath and by the
      stochastic theory. In motional narrowing regime, the spectra from the stochastic
      model are quite different from those from the LTC-QFP. In spectral diffusion
      regime, however, the 2D line shapes from the stochastic model resemble those from
      the LTC-QFP besides the blueshifts caused by the dissipation from the colored
      noise bath. The preconditions for validity of the stochastic theory for molecular
      vibrational motion are also discussed.

PMID- 16965024
TI  - Characterization of spectral diffusion from two-dimensional line shapes.
AB  - The analysis of line shapes in two-dimensional optical and infrared
      spectroscopies is a powerful approach to characterizing the dynamics of molecules
      in the condensed phase. Changes in line shape from diagonally elongated to
      symmetric as a function of waiting time arise from evolution of the transition
      frequency. We describe a number of quantitative measures of frequency
      fluctuations and spectral diffusion through the analysis of two-dimensional (2D)
      line shapes. These metrics are identical to the system's frequency correlation
      function and independent of population relaxation in the limit of a short time
      approximation for the 2D response. We also test the broader applicability of
      these expressions for analyzing three-level vibrational systems and experiments
      with finite pulses.

PMID- 16965025
TI  - Analysis of nucleation ability of cluster configurations with Monte Carlo
      simulations of argon.
AB  - We determine the nucleation ability of argon clusters from Monte Carlo
      simulations. The nucleation rate appears to be defined by a sole characteristic
      of the clusters, namely, the stability. The stability is calculated as the ratio
      of grand canonical growth and decay rates and can be assigned to individual
      cluster configurations. We study the connection between the stability of the
      cluster configurations and their volume and total potential energy. Neither the
      potential energy nor the volume of a cluster configuration has a clear relation
      to its stability, and thus to the nucleation ability. On the other hand, we show
      that it is possible to use a specific volume for each cluster size to calculate
      the work of the cluster formation. These clusters with a unique volume have the
      same average stability as the full set of clusters. Our simulation method allows
      us to study the effect of possible deviations from equilibrium in the cluster
      configuration distributions. We argue that the nucleation process itself can
      produce a source for such a deviation. We show that even a small deviation from
      equilibrium in the cluster configuration distribution can lead to a dramatic
      deceleration of the nucleation rate. Although our simulations may overestimate
      the magnitude of the effect, they give qualitative estimates for its importance.

PMID- 16965026
TI  - Correlation of hydrogen bond lengths and angles in liquid water based on Compton
      scattering.
AB  - The temperature-dependent hydrogen-bond geometry in liquid water is studied by x
      ray Compton scattering using synchrotron radiation combined with density
      functional theory analysis. Systematic changes, related to the weakening of
      hydrogen bonding, are observed in the shape of the Compton profile upon
      increasing the temperature. Using model calculations and published distribution
      functions of hydrogen-bond geometries obtained from a NMR study we find a
      significant correlation between the hydrogen-bond length and angle. This imposes
      a new constraint on the possible local structure distributions in liquid water.
      In particular, the angular distortions of the short hydrogen bonds are
      significantly restricted.

PMID- 16965027
TI  - Molecular dynamics simulations of melting of perfect crystalline hexahydro-1,3,5
      trinitro-1,3,5-s-triazine.
AB  - The melting mechanism of superheated perfect crystalline hexahydro-1,3,5-trinitro
      1,3,5-s-triazine (alpha-RDX) has been investigated using molecular dynamics
      simulations with the fully flexible force field developed by Smith and Bharadwaj
      [J. Phys. Chem. B 103, 3570 (1999)]. Sequential 50 ps equilibration simulations
      of the constant stress-constant temperature ensemble were performed at 10 K
      intervals over the range of 300-650 K, corresponding to a heating rate of 2.0 x
      10(11) Ks. A solid-solid phase transition is observed between 480 and 490 K,
      followed by melting, which occurs between 500 and 510 K. The solid-solid phase
      transition, both displacive and rotational, is characterized by an abrupt
      decrease in the lengths of the unit cell edges a and b and an increase of the
      length of edge c. The molecular conformation in the new phase is AAE, although
      the axial nitro groups have different changes: one shift is more axial and the
      other is more equatorial. Phases other than alpha-RDX have been observed
      experimentally, however, there are insufficient data for comparisons to ascertain
      that the new phase observed here corresponds to a real phase. At the high heating
      rate (2.0 x 10(11) Ks) used in the simulations, the melted RDX reaches full
      orientational disorder at about 540 K and translational freedom at around 580 K.
      If the simulation at the melting temperature (510 K) is run sufficiently long
      complete rotational freedom is achieved in a few hundreds of picoseconds, while
      complete translational freedom requires much longer. These results show that
      given a sufficiently high heating rate, the system can exist for significant
      periods of time in a near-liquid state in which the molecules are not as free to
      rotate and diffuse as in the true liquid state. The bond lengths and bond angles
      undergo little change upon melting, while there are significant changes in the
      dihedral angles. The molecular conformation of RDX changes from AAE to EEE upon
      melting. The ramification of this for formulating force fields that accurately
      describe melting is that it is important that the torsional motions are
      accurately described.

PMID- 16965028
TI  - Fifth-order two-dimensional Raman spectroscopy of liquid water, crystalline ice
      Ih and amorphous ices: sensitivity to anharmonic dynamics and local hydrogen bond
      network structure.
AB  - The theoretical study of off-resonant fifth-order two-dimensional (2D)-Raman
      spectroscopy is made to analyze the intermolecular dynamics of liquid and solid
      water. The 2D-Raman spectroscopy is susceptible to the nonlinear anharmonic
      dynamics and local hydrogen bond structure in water. It is found that the
      distinct 2D-Raman response appears as the negative signal near the t(2) axis. The
      origin of this negative signal for t(2)<15 fs is from the nonlinear
      polarizability in the librational motions, whereas that for 30 fs<t(2)<150 fs is
      attributed to the anharmonic translational motions. It is found that the
      mechanical anharmonicity and nonlinear polarizability couplings among modes
      clearly can be observed as the sum- and difference-frequency peaks in the 2D
      Raman spectrum (i.e., Fourier transforms of the response). The 2D-Raman
      spectroscopies of ice Ih and amorphous ices, i.e., low density, high density, and
      very high density amorphous ices, are also investigated. It is found that the 2D
      Raman spectroscopy is very sensitive to the anisotropy of the structure of ice
      Ih. The strong hydrogen bond stretching band is seen in the 2D-Raman spectroscopy
      of the polarization directions parallel to the c axis, whereas the contributions
      of the librational motion can be also seen in the spectrum with the polarization
      directions parallel to the a axis. The 2D-Raman spectroscopy is also found to be
      also very sensitive to the differences in local hydrogen bond network structures
      in various amorphous phases.

PMID- 16965029
TI  - Hydrogen network fluctuations of associating liquids: dielectric relaxation of
      ethylene glycol oligomers and their mixtures with water.
AB  - Complex dielectric spectra of ethylene glycol and of various derivatives as well
      as of mixtures of water with an ethylene glycol oligomer and with a poly(ethylene
      glycol) dimethyl ether oligomer have been measured. The spectra can be well
      represented by a Cole-Cole [Cole and Cole, J. Chem. Phys. 9, 341 (1941)] spectral
      function. The extrapolated low frequency (static) permittivity of this function
      has been evaluated to yield the effective dipole orientation correlation factor
      of the liquids. The relaxation time of the ethylene glycols displays a
      characteristic dependence upon the ratio of concentrations of hydrogen bond
      donating and accepting groups, indicating two opposing effects. With increasing
      availability of hydrogen bonding sites effects of association and also of
      dynamical destabilization increase. Both effects exist also in the mixture of
      water with the oligomers. They are discussed in terms of a wait-and-switch model
      of dipole reorientation in associating liquids. Another feature in the dependence
      of the dielectric relaxation time of poly(ethylene glycol)/water mixtures upon
      mixture composition has been tentatively assigned to precritical demixing
      behavior of the binary liquids in some temperature range.

PMID- 16965030
TI  - Thermodynamic properties of short-range square well fluid.
AB  - The interfacial properties of short-range square well fluid with lambda=1.15,
      1.25, and 1.375 were determined by using single canonical Monte Carlo
      simulations. Simulations were carried out in the vapor-liquid region. The
      coexistence curves of these models were calculated and compared to those
      previously reported in the literature and good agreement was found among them. We
      found that the surface tension curves for any potential model of short range form
      a single master curve when we plot gamma* vs TT(c). It is demonstrated that the
      critical reduced second virial coefficient B(2)* as a function of interaction
      range or T(c)* is not constant.

PMID- 16965031
TI  - Analysis of kinetic isotope effects for nonadiabatic reactions.
AB  - Factors influencing the rates of quantum mechanical particle transfer reactions
      in many-body systems are discussed. The investigations are carried out on a
      simple model for a proton transfer reaction that captures generic features seen
      in more realistic models of condensed phase systems. The model involves a
      bistable quantum oscillator coupled to a one-dimensional double-well reaction
      coordinate, which is in turn coupled to a bath of harmonic oscillators. Reactive
      flux correlation functions that involve quantum-classical Liouville dynamics for
      chemical species operators and quantum equilibrium sampling are used to estimate
      the reaction rates. Approximate analytical expressions for the quantum
      equilibrium structure are derived. Reaction rates are shown to be influenced
      significantly by both the quantum equilibrium structure and nonadiabatic
      dynamics. Nonadiabatic dynamical effects are found to play the major role in
      determining the magnitude of the kinetic isotope effect for the model transfer
      reaction.

PMID- 16965032
TI  - Computational studies on thermodynamic properties, effective diameters, and free
      volume of argon using an ab initio potential.
AB  - A quantum mechanical derived ab initio interaction potential for the argon dimer
      was tested in molecular simulations to reproduce the thermophysical properties of
      the vapor-liquid phase equilibria using the Gibbs ensemble Monte Carlo
      simulations as well as the liquid and supercritical equation of state using the
      NVT Monte Carlo simulations. The ab initio interaction potential was taken from
      the literature. A recently developed theory [R. Laghaei et al., J. Chem. Phys.
      124, 154502 (2006)] was used to compute the effective diameters of argon in fluid
      phases and the results were subsequently applied in the generic van der Waals
      theory to compute the free volume of argon. The calculated densities of the
      coexisting phases, the vapor pressure, and the equation of state show excellent
      agreement with experimental values. The effective diameters and free volumes of
      argon are given over a wide range of densities and temperatures. An empirical
      formula was used to fit the effective diameters as a function of density and
      temperature. The computed free volume will be used in future investigations to
      calculate the transport properties of argon.

PMID- 16965033
TI  - Fractal growth mechanism of sp3-bonded 5H-BN microcones by plasma-assisted pulsed
      laser chemical vapor deposition.
AB  - Here we propose a repetitive photochemical reaction and diffusion model for the
      fractal pattern formation of sp(3)-bonded 5H-BN microcones in laser-assisted
      plasma chemical vapor deposition, which was observed experimentally and reported
      previously. This model describing the behavior of the surface density of
      precursor species gave explanations to (1) the "line-drawing" nature of the
      patterns, (2) the origin of the scale-invariant self-similarity (fractality) of
      the pattern, and (3) the temperature-dependent uniform to fractal transition. The
      results have implications for controlling the self-organized arrangements of
      electron-emitter cones at the micro-and nanoscale by adjusting macroscopically
      the boundary condition (L(X),L(Y)) for the deposition, which will be very
      effective in improving the electron field emission properties.

PMID- 16965034
TI  - Hydrodynamic lubrication in nanoscale bearings under high shear velocity.
AB  - The setting up process in a nanoscale bearing has been modeled by molecular
      dynamics simulation. Contrary to the prediction from the classical Reynolds'
      theory, simulation results show that the load capacity of the nanoscale bearing
      does not increase monotonically with the operation speed. This is attributed to
      the change of the local shear rate, which will decrease with the shear velocity
      of the bearing as the shear velocity exceeds a critical value, i.e., the local
      shear rate has an upper limit. A simple nonlinear dynamic model indicates that
      the momentum exchange between the liquid and the solid wall is reduced with the
      shear velocity when the shear velocity is above a critical value. The weak
      momentum exchange results in a decrease of the local shear rate, which in turn
      causes a sharp increase of the slip length.

PMID- 16965035
TI  - What really enhances the adsorption of polymers onto chemically nonuniform
      surfaces: surface randomness or its heterogeneity?
AB  - We theoretically perform a comparative analysis of the adsorption of polymers
      onto the regularly and randomly nonuniform surfaces. By developing and making use
      of the self-consistent perturbation expansion we calculate the surface excesses
      of the polymers adsorbed on the random and periodically patterned surfaces. In
      both cases the enhancement of the polymer adsorption is indicated, as compared to
      the adsorption onto the homogeneous surface that has the same average affinity
      for polymers. Moreover, the results obtained for the randomly nonuniform and
      periodically patterned adsorbing surfaces show striking quantitative similarity,
      when compared at the same characteristic sizes of inhomogeneities of these
      surfaces. This finding leads to the conclusion that the adsorption ability of the
      nonuniform surface primarily depends on the characteristic size of the surface
      inhomogeneity, rather than on the spatial distribution of the inhomogeneities on
      this surface. In all cases, the calculated total surface excess is found to be a
      decaying function of the ratio of the radius of gyration of polymers to the
      characteristic size of the surface inhomogeneity. The effect of the excluded
      volume is found to reduce the polymer adsorption.

PMID- 16965036
TI  - Pinning of size-selected Pd nanoclusters on graphite.
AB  - The production of stable cluster arrays on smooth surfaces has several potential
      technological applications. We report a study of the pinning of size-selected
      palladium nanoclusters on the graphite surface. The clusters formed during gas
      aggregation in vacuum are projected with sufficient kinetic energy to create a
      defect in the graphite surface. The energy necessary to create such an
      immobilizing defect is investigated as a function of the palladium cluster size.
      The palladium pinning energy is found to deviate from the simple binary collision
      model as appropriate to previously reported silver and gold results. This finding
      is in agreement with the deviation of nickel clusters and points to the influence
      of the interatomic cluster bonding on the mechanics of the collision.

PMID- 16965037
TI  - Ni adsorption on Stone-Wales defect sites in single-wall carbon nanotubes.
AB  - Ni adsorption on Stone-Wales defect sites in (10,0) zigzag and (5,5) armchair
      single-wall carbon nanotubes was studied using the density functional theory. The
      stable adsorption sites and their binding energies on different Stone-Wales
      defect types were analyzed and compared to those on perfect side walls. It was
      determined that the sites formed via fusions of 7-7 and 6-7 rings are the most
      exothermic in the cases of (10,0) and (5,5) defective tubes. In addition C-C
      bonds associated with Stone-Wales defects are more reactive than the case for a
      perfect hexagon, thus enhancing the stability of the Ni adsorption. Moreover, the
      Ni adsorption was found to show a noticeable relationship to the orientation of
      the Stone-Wales defects with respect to the tube axis. The nature of the Ni
      adsorption on Stone-Wales defects that have the similar orientation is identical,
      in spite of the different chiralities.

PMID- 16965038
TI  - Forming chainlike filaments of magnetic colloids: the role of the relative
      strength of isotropic and anisotropic particle interactions.
AB  - The influence of the interplay between anisotropic magnetic and isotropic
      electrostatic interactions on the aggregation behavior of aqueous suspensions of
      electric double layered magnetic particles was studied. Therefore, the particles
      were aggregated under the action of an external magnetic field and in the
      presence of different amounts of an indifferent 1:1 electrolyte. After removing
      the field, linear aggregates remained in the sample. Static light scattering and
      electron micrographs confirmed the chainlike cluster morphology. Dynamic light
      scattering was used for monitoring the average diffusion coefficient of these
      magnetic filaments. A theoretical model that allows the experimental mean
      diffusion coefficient to be related to the average chain length was successfully
      employed. The results show that, at fixed exposure time and field strength, the
      average filament size is proportional to the amount of electrolyte added. The
      light scattering data and transmission electron microscopy micrographs prove that
      permanent chains coexist with a relatively large fraction of individual particles
      when no or little electrolyte was added to the samples. A plausible explanation
      for this "selective aggregation" phenomenon could be given in terms of surface
      charge heterogeneities. The chain growth was found to follow a power law with a
      similar exponent for all the electrolyte concentrations studied. Scaling theories
      were employed for estimating the ratio of particles taking part in the
      aggregation process.

PMID- 16965039
TI  - Adsorption of O2 on tubelike Au24 and Au24- clusters.
AB  - The nondissociative adsorptions of O(2) on the neutral and anionic Au(24) have
      been studied using the density functional theory (DFT) in the generalized
      gradient approximation. Their geometrical structures are optimized by using a
      combination of the relativistic effective core potential and all-electron
      potential with scalar relativistic corrections. It is found that the adsorptions
      of O(2) on the tubelike Au(24) and Au(24) (-) are more stable than it on their
      space-filled counterparts. Mulliken population analysis shows that the O(2)
      adsorbed on the tubelike Au(24) and Au(24) (-) got more electrons than on the
      amorphous ones, which may be a reason why the O(2) can be adsorbed more easily on
      the former rather than on the latter. Compared with the previous DFT studies of
      O(2) adsorbed on small Au(n) (n< or =10) clusters, we have shown that the O(2)
      can also be adsorbed on the neutral even Au(24) with an adsorption energy
      compatible with that on the small neutral odd gold clusters, but the adsorption
      energy of O(2) on the anionic Au(24) (-) is lower than that on the small anionic
      Au(n) with even n. In all the optimized geometrical structures of the O(2)
      adsorbed Au(24) and Au(24) (-) clusters, including both tubelike and amorphous
      ones, we found that O(2) prefers its two O atoms to be attached to two near gold
      atoms with the least coordination number rather than only one O atom to be
      attached to one gold atom.

PMID- 16965040
TI  - Theoretical study of the photodesorption mechanism of nitric oxide on a Ag(111)
      surface: a nonequilibrium Green's function approach to hot-electron tunneling.
AB  - The photoinduced desorption of NO molecules on a Ag surface was studied
      theoretically using a recently developed method based on the nonequilibrium
      Green's function approach combined with the density functional theory. Geometry
      optimizations for the stable NO dimer phase were carried out, and two structures
      of adsorbed dimers were identified. We calculated the reaction probabilities as a
      function of incident photon energy for each of the dimers and compared them with
      experimental action spectra. The two main features of the action spectra, (i) a
      long tail to the long wavelength (approximately 600 nm) and (ii) a rapid increase
      at approximately 350 nm, were well reproduced. By theoretical analysis, we found
      the importance of quantum interference for the interfacial charge transfer
      between the metal substrate and the adsorbate, as well as the contribution of
      secondary electrons. Our calculations suggest that the photoactive species is
      dimeric and that the resonant level is single for the photodesorption of NO.

PMID- 16965041
TI  - Theoretical model of infrared spectra of hydrogen bonds in molecular crystals and
      its application to interpretation of infrared spectra of 1-methylthymine.
AB  - A theoretical model for vibrational interactions in the hydrogen bonds in
      molecular crystals with four molecules forming two centrosymmetric dimers in the
      unit cell is presented. The model takes into account anharmonic-type couplings
      between the high-frequency N-H(D) and the low-frequency N...O stretching
      vibrations in each hydrogen bond, resonance interactions (Davydov coupling)
      between equivalent hydrogen bonds in each dimer, resonance interdimer
      interactions within a unit cell, and Fermi resonance between the N-H(D)
      stretching fundamental and the first overtone of the N-H(D) in-plane bending
      vibrations. The vibrational Hamiltonian, selection rules, and expressions for the
      integral properties of an absorption spectrum are derived. The model is used for
      theoretical simulation of the NH stretching bands of 1-methylthymine and its ND
      derivative at 300 K. The effect of deuteration is successfully reproduced by our
      model. Infrared, far-infrared, Raman, and low-frequency Raman spectra of 1
      methylthymine and its deuterated derivative have been measured. Experimental
      geometry and frequencies are compared with the results of density functional
      theory calculations performed at the B3LYP6-311++G**, B3LYP/cc-pVTZ, B3PW916
      311++G**, and B3PW91/cc-pVTZ levels.

PMID- 16965042
TI  - Self-consistent study of single molecular transistor modulated by transverse
      field.
AB  - We use a self-consistent method to study the current of the single molecular
      transistor modulated by the transverse field in the level of the density
      functional theory and the nonequilibrium Green function method. The numerical
      results show that both the polyacene-dithiol molecules and the fused-ring
      thiophene molecules are the potential high-frequency molecular transistors
      controlled by the transverse field. The longer molecules of the polyacene-dithiol
      or the fused-ring thiophene are in favor of realizing the gate-bias controlled
      molecular transistor. The theoretical results suggest the related experiments.

PMID- 16965043
TI  - Effect of confinement by porous carbons on the unimolecular decomposition of
      formaldehyde.
AB  - As part of an effort to understand the effect of confinement by porous carbons on
      chemical reactions, we have carried out density functional theory calculations on
      the unimolecular decomposition of formaldehyde within graphitic carbons. Our
      results show that the interactions with the carbon walls result in a lowering of
      the reaction barrier. For larger pores, there is also a shift of the equilibrium
      towards the formation of carbon monoxide and hydrogen at low temperatures. This
      trend is reversed for small pore sizes.

PMID- 16965044
TI  - High translational energy release in H2 (D2) associative desorption from H (D)
      chemisorbed on C(0001).
AB  - Highly energetic translational energy distributions are reported for hydrogen and
      deuterium molecules desorbing associatively from the atomic chemisorption states
      on highly oriented pyrolytic graphite (HOPG). Laser assisted associative
      desorption is used to measure the time of flight of molecules desorbing from a
      hydrogen (deuterium) saturated HOPG surface produced by atomic exposure from a
      thermal atom source at around 2100 K. The translational energy distributions
      normal to the surface are very broad, from approximately 0.5 to approximately 3
      eV, with a peak at approximately 1.3 eV. The highest translational energy
      measured is close to the theoretically predicted barrier height. The angular
      distribution of the desorbing molecules is sharply peaked along the surface
      normal and is consistent with thermal broadening contributing to energy release
      parallel to the surface. All results are in qualitative agreement with recent
      density functional theory calculations suggesting a lowest energy para-type dimer
      recombination path.

PMID- 16965045
TI  - Ion permeation dynamics in carbon nanotubes.
AB  - Molecular dynamics simulations are carried out to investigate the permeation of
      ions and water in a membrane consisting of single wall carbon nanotubes
      possessing no surface charges connecting two reservoirs. Our simulations reveal
      that there are changes in the first hydration shell of the ions upon confinement
      in tubes of 0.82 or 0.90 nm effective internal diameter. Although the first
      minimum in the g(r) is barely changed in the nanotube compared to in the bulk
      solution, the hydration number of Na(+) ion is reduced by 1.0 (from 4.5 in bulk
      to 3.5 in the 0.90 nm tube) and the hydration number is reduced further in the
      0.82 nm tube. The changes in the hydration shell of Cl(-) ion are negligible,
      within statistical errors. The water molecules of the first hydration shell of
      both ions exchange less frequently inside the tube than in the bulk solution. We
      compare ion trajectories for ions in the same tube under identical reservoir
      conditions but with different numbers of ions in the tubes. This permits
      investigation of changes in structure and dynamics which arise from multiple ion
      occupancy in a carbon nanotube possessing no surface charges. We also
      investigated the effects of tube flexibility. Ions enter the tubes so as to form
      a train of ion pairs. We find that the radial distribution profiles of Na(+) ions
      broaden significantly systematically with increasing number of ion pairs in the
      tube. The radial distribution profiles of Cl(-) ions change only slightly with
      increasing number of ions in the tube. Trajectories reveal that Na(+) ions do not
      pass each other in 0.90 nm tubes, while Cl(-) ions pass each other, as do ions of
      opposite charge. An ion entering the tube causes the like-charged ions preceding
      it in the tube to be displaced along the tube axis and positive or negative ions
      will exit the tube only when one or two other ions of the same charge are present
      in the tube. Thus, the permeation mechanism involves multiple ions and Coulomb
      repulsion among the ions plays an essential role.

PMID- 16965046
TI  - Theoretical assessment of the elastic constants and hydrogen storage capacity of
      some metal-organic framework materials.
AB  - Metal-organic frameworks (MOFs) are promising materials for applications such as
      separation, catalysis, and gas storage. A key indicator of their structural
      stability is the shear modulus. By density functional theory calculations in a
      106-atom supercell, under the local density approximation, we find c(11)=29.2 GPa
      and c(12)=13.1 GPa for Zn-based MOF 5. However, we find c(44) of MOF-5 to be
      exceedingly small, only 1.4 GPa at T=0 K. The binding energy E(ads) of a single
      hydrogen molecule in MOF-5 is evaluated using the same setup. We find it to be 
      0.069 to -0.086 eVH(2) near the benzene linker and -0.106 to -0.160 eVH(2) near
      the Zn(4)O tetrahedra. Substitutions of chlorine and hydroxyl in the benzene
      linker have negligible effect on the physisorption energies. Pentacoordinated
      copper (and aluminum) in a framework structure similar to MOF-2 gives E(ads)
      approximately -0.291 eVH(2) (and -0.230 eVH(2)), and substitution of nitrogen in
      benzene (pyrazine) further enhances E(ads) near the organic linker to -0.16
      eVH(2), according to density functional theory with local density approximation.

PMID- 16965047
TI  - Large dielectric susceptibility associated with proton transfer in a
      supramolecular structure of chloranilic acid and 5,5'-dimethyl-2,2'-bipyridine.
AB  - A 1:1 adduct of chloranilic acid with 5,5'-dimethyl-2,2'-bipyridine, in which two
      kinds of molecules are connected by infinite hydrogen bond chains, exhibits a
      distinct dielectric phase transition when cooled. Below T(c)(=318 K) the hydrogen
      atoms participating in hydrogen bonding undergo long-range ordering and form an
      antiferroelectric-like state, taking a single minimum potential in the high
      temperature phase (T>T(c)) due to the bifurcate hydrogen bond system. The proton
      transfer phenomenon was clearly observed by electron density distribution
      analysis using a maximum entropy method of synchrotron x-ray diffraction data.

PMID- 16965048
TI  - Phase equilibria and plate-fluid interfacial tensions for associating hard sphere
      fluids confined in slit pores.
AB  - The excess Helmholtz free energy functional for associating hard sphere fluid is
      formulated by using a modified fundamental measure theory [Y. X. Yu and J. Z. Wu,
      J. Chem. Phys. 117, 10156 (2002)]. Within the framework of density functional
      theory, the thermodynamic properties including phase equilibria for both
      molecules and monomers, equilibrium plate-fluid interfacial tensions and
      isotherms of excess adsorption, average molecule density, average monomer
      density, and plate-fluid interfacial tension for four-site associating hard
      sphere fluids confined in slit pores are investigated. The phase equilibria
      inside the hard slit pores and attractive slit pores are determined according to
      the requirement that temperature, chemical potential, and grand potential in
      coexistence phases should be equal and the plate-fluid interfacial tensions at
      equilibrium states are predicted consequently. The influences of association
      energy, fluid-solid interaction, and pore width on phase equilibria and
      equilibrium plate-fluid interfacial tensions are discussed.

PMID- 16965049
TI  - Translational to rotational energy transfer in molecule-surface collisions.
AB  - A theoretical approach that combines classical mechanics for treating
      translational and rotational degrees of freedom and quantum mechanics for
      describing the excitation of internal molecular modes is applied to the
      scattering of diatomic molecules from metal surfaces. Calculations are carried
      out for determining the extent of energy transfer to the rotational degrees of
      freedom of the projectile molecule. For the case of observed spectra of intensity
      versus final rotational energy, quantitative agreement with available
      experimental data for the scattering of NO and N(2) from close packed metal
      surfaces is obtained. It is shown that such measurements can be used to determine
      the average rotational energy of the incident molecular beam. Measurements of the
      exchange of energy between translational and rotational degrees of freedom upon
      collision are also described by calculations for these same systems.

PMID- 16965050
TI  - Theoretical description of the adsorption and the wetting behavior of alkanes on
      water.
AB  - The wetting behavior of alkanes of medium chain length (e.g., pentane, hexane,
      and heptane) on water is more complex than the usually observed first-order
      wetting transition from partial to complete wetting by showing a sequence of two
      transitions. In this sequential-wetting scenario, a first-order transition from a
      microscopically thin to a mesoscopically thick layer of liquid on the substrate
      surface is followed by a continuous divergence of the film thickness upon
      increase of the temperature. This critical transition to complete wetting at
      T(w,c) is solely determined by long-range interactions between substrate and
      adsorbate, which are well-described by Dzyaloshinskii-Lifshitz-Pitaevskii [Adv.
      Phys. 10, 165 (1961)] theory in terms of the static dielectric constants and the
      refractive indices of the media involved. The first-order thin-thick transition,
      however, which occurs at a lower temperature T(w,1), results from an interplay of
      short-range and long-range forces and is notoriously more difficult to describe
      because a satisfactory theory of the short-range interactions between substrate
      and adsorbate is still missing. The approach presented in this paper attempts to
      account for the short-range interactions in an effective way: Within a Cahn-type
      [J. Chem. Phys. 66, 3667 (1977)] theory that has been augmented for long-range
      interactions and modified to treat the first layer of adsorbed molecules in a
      lattice-gas approach, the contact energy is deduced from the surface pressure,
      which in turn is calculated using a two-dimensional van der Waals equation of
      state and an expression for the Henry's law constant that was derived by Hirasaki
      [J. Adhes. Sci. Technol. 7, 285 (1993)]. The method uses only the dielectric
      properties of the isolated bulk media and simple assumptions on the size and the
      shape of the adsorbed alkane molecules and leads to satisfactory results for the
      transition temperatures T(w,1) and T(w,c).

PMID- 16965051
TI  - Parallelized-over-parts computation of absolute binding free energy with docking
      and molecular dynamics.
AB  - We present a technique for biomolecular free energy calculations that exploits
      highly parallelized sampling to significantly reduce the time to results. The
      technique combines free energies for multiple, nonoverlapping configurational
      macrostates and is naturally suited to distributed computing. We describe a
      methodology that uses this technique with docking, molecular dynamics, and free
      energy perturbation to compute absolute free energies of binding quickly compared
      to previous methods. The method does not require a priori knowledge of the
      binding pose as long as the docking technique used can generate reasonable
      binding modes. We demonstrate the method on the protein FKBP12 and eight of its
      inhibitors.

PMID- 16965053
TI  - Fluorescence correlation spectroscopy analysis of segmental dynamics in actin
      filaments.
AB  - We adapt fluorescence correlation spectroscopy (FCS) formalism to the studies of
      the dynamics of semiflexible polymers and derive expressions relating FCS
      correlation function to the longitudinal and transverse mean-square displacements
      of polymer segments. The obtained relations do not depend on any specific model
      of polymer dynamics. We use the derived expressions to measure the dynamics of
      actin filaments in two experimental situations: filaments labeled at distinct
      positions and homogeneously labeled filaments. Both approaches give consistent
      results and allow to measure the temporal dependence of the segmental mean-square
      displacement over almost five decades in time, from approximately 40 micros to
      approximately 2 s. These noninvasive measurements allow for a detailed
      quantitative comparison of the experimental data to the current theories of
      semiflexible polymer dynamics. Good quantitative agreement is found between the
      experimental results and theories explicitly accounting for the hydrodynamic
      interactions between polymer segments.

PMID- 16965052
TI  - On the use of orientational restraints and symmetry corrections in alchemical
      free energy calculations.
AB  - Alchemical free energy calculations are becoming a useful tool for calculating
      absolute binding free energies of small molecule ligands to proteins. Here, we
      find that the presence of multiple metastable ligand orientations can cause
      convergence problems when distance restraints alone are used. We demonstrate that
      the use of orientational restraints can greatly accelerate the convergence of
      these calculations. However, even with this acceleration, we find that sufficient
      sampling requires substantially longer simulations than are used in many
      published protocols. To further accelerate convergence, we introduce a new method
      of configuration space decomposition by orientation which reduces required
      simulation lengths by at least a factor of 5 in the cases examined. Our method is
      easily parallelizable, well suited for cases where a ligand cocrystal structure
      is not available, and can utilize initial orientations generated by docking
      packages.

PMID- 16965054
TI  - Frustration and hydrophobicity interplay in protein folding and protein
      evolution.
AB  - A lattice model is used to study mutations and compacting effects on protein
      folding rates and folding temperature. In the context of protein evolution, we
      address the question regarding the best scenario for a polypeptide chain to fold:
      either a fast nonspecific collapse followed by a slow rearrangement to form the
      native structure or a specific collapse from the unfolded state with the
      simultaneous formation of the native state. This question is investigated for
      optimized sequences, whose native state has no frustrated contacts between
      monomers, and also for mutated sequences, whose native state has some degree of
      frustration. It is found that the best scenario for folding may depend on the
      amount of frustration of the native structure. The implication of this result on
      protein evolution is discussed.

PMID- 16965055
TI  - Effect of dipolar moments in domain sizes of lipid bilayers and monolayers.
AB  - Lipid domains are found in systems such as multicomponent bilayer membranes and
      single component monolayers at the air-water interface. It was shown by Keller et
      al. [J. Phys. Chem. 91, 6417 (1987)] that in monolayers, the size of the domains
      results from balancing the line tension, which favors the formation of a large
      single circular domain, against the electrostatic cost of assembling the dipolar
      moments of the lipids. In this paper, we present an exact analytical expression
      for the electric potential, ion distribution, and electrostatic free energy for
      different problems consisting of three different slabs with different dielectric
      constants and Debye lengths, with a circular homogeneous dipolar density in the
      middle slab. From these solutions, we extend the calculation of domain sizes for
      monolayers to include the effects of finite ionic strength, dielectric
      discontinuities (or image charges), and the polarizability of the dipoles and
      further generalize the calculations to account for domains in lipid bilayers. In
      monolayers, the size of the domains is dependent on the different dielectric
      constants but independent of ionic strength. In asymmetric bilayers, where the
      inner and outer leaflets have different dipolar densities, domains show a strong
      size dependence with ionic strength, with molecular-sized domains that grow to
      macroscopic phase separation with increasing ionic strength. We discuss the
      implications of the results for experiments and briefly consider their relation
      to other two dimensional systems such as Wigner crystals or heteroepitaxial
      growth.

PMID- 16965056
TI  - Effect of orientation in translocation of polymers through nanopores.
AB  - The motion of polymers with inhomogeneous structure through nanopores is
      discussed theoretically. Specifically, we consider the translocation dynamics of
      polymers consisting of double-stranded and single-stranded blocks. Since only the
      single-stranded chain can go through the nanopore the double-stranded segment has
      to unzip before the translocation. Utilizing a simple analytical model,
      translocation times are calculated explicitly for different polymer orientations,
      i.e., when the single-stranded block enters the pore first and when the double
      stranded segment is a leading one. The dependence of the translocation dynamics
      on external fields, energy of interaction in the double-stranded segment, size of
      the polymer, and the fraction of double-stranded monomers is analyzed. It is
      found that the order of entrance into the pore has a significant effect on the
      translocation dynamics. The theoretical results are discussed using free-energy
      landscape arguments.

PMID- 16965057
TI  - Viscoelasticity of mono- and polydisperse inverse ferrofluids.
AB  - We report on measurements of a magnetorheological model fluid created by
      dispersing nonmagnetic microparticles of polystyrene in a commercial ferrofluid.
      The linear viscoelastic properties as a function of magnetic field strength,
      particle size, and particle size distribution are studied by oscillatory
      measurements. We compare the results with a magnetostatic theory proposed by De
      Gans et al. [Phys. Rev. E 60, 4518 (1999)] for the case of gap spanning chains of
      particles. We observe these chain structures via a long distance microscope. For
      monodisperse particles we find good agreement of the measured storage modulus
      with theory, even for an extended range, where the linear magnetization law is no
      longer strictly valid. Moreover we compare for the first time results for mono-
      and polydisperse particles. For the latter, we observe an enhanced storage
      modulus in the linear regime of the magnetization.

PMID- 16965058
TI  - A toy model of polymer stretching.
AB  - We present an extremely simplified model of multiple-domain polymer stretching in
      an atomic force microscopy experiment. We portray each module as a binary set of
      contacts and decompose the system energy into a harmonic term (the cantilever)
      and long-range interaction terms inside each domain. Exact equilibrium
      computations and Monte Carlo simulations qualitatively reproduce the experimental
      sawtooth pattern of force-extension profiles, corresponding (in our model) to
      first-order phase transitions. We study the influence of the coupling induced by
      the cantilever and the pulling speed on the relative heights of the force peaks.
      The results suggest that the increasing height of the critical force for
      subsequent unfolding events is an out-of-equilibrium effect due to a finite
      pulling speed. The dependence of the average unfolding force on the pulling speed
      is shown to reproduce the experimental logarithmic law.

PMID- 16965059
TI  - A kinetic theory of tertiary contact formation coupled to the helix-coil
      transition in polypeptides.
AB  - The framework model and the hydrophobic collapse model represent two canonical
      descriptions of the protein folding process. The first places primary reliance on
      the short-range interactions of secondary structure and the second assigns
      greater importance to the long-range interactions of tertiary structure. The
      availability of increasingly detailed information about the folding mechanisms of
      diverse proteins suggests that both are important and the folding mechanism of
      most proteins utilizes different combinations of such interactions. A prior
      report described the XHC model, an extended helix-coil theory, which treats the
      mutual stabilization of secondary and tertiary structure in simple alpha-helical
      proteins at equilibrium. In this study, a kinetic scheme describing tertiary
      contact formation has been developed which relaxes to the XHC equilibrium model.
      The relaxation is governed by the relative stabilities of the equilibrium states
      and an additional factor which represents an activation energy for formation of a
      tertiary contact. The model can be used to simulate time-dependent properties of
      the ensemble of conformations during the entire folding process, and the
      resulting predictions are applicable to a range of experimental methods. This XHC
      kinetic model enables investigation of the relative influence of secondary and
      tertiary interactions on folding mechanisms.

PMID- 16965060
TI  - Depletion potential between large spheres immersed in a multicomponent mixture of
      small spheres.
AB  - We analyze the depletion potential between large spheres in a multicomponent
      mixture of dense small spheres (up to seven components) using the integral
      equation theory (IET), in which semiempirical bridge functions are incorporated,
      and the insertion approach within the framework of density functional theory
      (DFT). The diameters of the small spheres considered are in the range of d(S)
      5d(S). The results from the IET and DFT are in close agreement with each other.
      The depletion potential in the mixture is substantially different from that in a
      one-component system of dense small spheres with diameter d(S). In comparison
      with the latter, the former possesses in general a less pronounced oscillatory
      structure, and the free-energy barrier for large spheres to overcome before
      reaching the contact is significantly reduced. This tendency can be enhanced as
      the number of components increases. In a several-component mixture of small
      spheres whose diameters are suitably chosen and in which the packing fractions of
      the components share the same value, the depletion potential is essentially short
      ranged and attractive and possesses a sufficiently large, negative value at the
      contact.

PMID- 16965061
TI  - The conformations of the amyloid-beta (21-30) fragment can be described by three
      families in solution.
AB  - Alzheimer's disease has been linked to the self-assembly of the amyloid-beta
      protein of 40 and 42 residues. Although monomers are in equilibrium with higher
      order species ranging from dimers to heptamers, structural knowledge of the
      monomeric amyloid-beta (Abeta) peptides is an important issue. Recent
      experimental data have shown that the fragment (21-30) is protease-resistant
      within full-length Abeta peptides and displays two structural families in
      solution. Because the details of the Abeta(21-30) structures found using distinct
      force fields and protocols differ at various degrees from those of the NMR
      structures, we revisit the conformational space of this peptide using the
      activation-relaxation technique (ART nouveau) coupled with a coarse-grained force
      field (OPEP v.3.0). We find that although Abeta(21-30) does not have a secondary
      structure, it dominantly populates three structural families, with a loop
      spanning residues Val24-Lys28. The first two families, which differ in the nature
      of the electrostatic interactions, satisfy the five interproton rotating frame
      nuclear Overhauser effect spectroscopy (ROESY) distances and superpose well onto
      the NMR structures. The third family, which cannot be seen by ROESY NMR
      experiments, displays a more open structure. This numeric study complements the
      experimental results by providing a much more detailed description of the
      dominant structures. Moreover, it provides further evidence of the capability of
      ART OPEP in providing a reliable conformational picture of peptides in solution.

PMID- 16965062
TI  - Coupling between hydration layer dynamics and unfolding kinetics of HP-36.
AB  - We have performed atomistic molecular dynamics simulations of aqueous solutions
      of HP-36 at 300 K in its native state, as well as at high temperatures to explore
      the unfolding dynamics of the protein and its correlation with the motion of
      water around it. On increasing the temperature a partially unfolded molten
      globule state is formed where the smallest alpha helix (helix 2) unfolds into a
      coil. It is observed that the unfolding is initiated around the residue Phe-18
      which shows a sharp displacement during unfolding. We have noticed that the
      unfolding of the protein affects the density of water near the protein surface.
      Besides, the dynamics of water in the protein hydration layer has been found to
      be strongly correlated with the time evolution of the unfolding process. We have
      introduced and calculated a displacement time correlation function to monitor the
      change in water motion relative to the protein backbone during unfolding. We find
      that the unfolding of helix 2 is associated with an increase in mobility of water
      around it as compared to water around the other two helices. We have also
      explored the microscopic aspects of secondary structure specific and site
      specific solvation dynamics of the protein. The calculations reveal that
      unfolding influences the solvation dynamics of the protein molecule in a
      heterogeneous manner depending on the location of the polar probe residues. This
      seems to be in agreement with recent experimental findings.

PMID- 16965063
TI  - Insight into the solvent effect: a density functional theory study of cisplatin
      hydrolysis.
AB  - The solvent effect on reactions in solutions is crucial for many systems. In this
      study, the reaction barrier with respect to the number of solvent molecules
      included in the system is systematically studied using density function theory
      calculations. Our results show that the barriers rapidly converge with respect to
      the number of solvent molecules. The solvent effect is investigated by
      calculating cisplatin hydrolysis in several types of solvents. The results are
      analyzed and a linear relationship between the reaction barrier and the
      interaction strength of solvent-reactants is found. Insight into the general
      solvent effect is obtained.

PMID- 16965065
TI  - Revelation of non-statistical behavior in HO2 vibration by a new ab initio
      potential energy surface.
AB  - The hydroperoxyl radical (HO2) has long been considered as a prototype for
      statistical vibrational dynamics. In this work, however, it is shown that the
      bound state energy levels (up to the dissociation threshold) and low-lying
      resonances of the HO2 system (J=0) obtained on a new ab initio potential energy
      surface exhibit surprisingly large regularity. The implications of the non
      statistical behavior of the HO2 system in unimolecular and bimolecular reactions
      are discussed.

PMID- 16965064
TI  - Ice-surface adsorption enhanced colligative effect of antifreeze proteins in ice
      growth inhibition.
AB  - This Communication describes a mechanism to explain antifreeze protein's function
      to inhibit the growth of ice crystals. We propose that the adsorption of
      antifreeze protein (AFP) molecules on an ice surface induces a dense AFP-water
      layer, which can significantly decrease the mole fraction of the interfacial
      water and, thus, lower the temperature for a seed ice crystal to grow in a super
      cooled AFP solution. This mechanism can also explain the nearly unchanged melting
      point for the ice crystal due to the AFP's ice-surface adsorption. A mathematical
      model combining the Langmuir theory of adsorption and the colligative effect of
      thermodynamics has been proposed to find the equilibrium constants of the ice
      surface adsorptions, and the interfacial concentrations of AFPs through fitting
      the theoretical curves to the experimental thermal hysteresis data. This model
      has been demonstrated by using the experimental data of serial size-mutated
      beetle Tenebrio molitor (Tm) AFPs. It was found that the AFP's ice-surface
      adsorptions could increase the interfacial AFP's concentrations by 3 to 4 orders
      compared with those in the bulk AFP solutions.

PMID- 16965066
TI  - Microsolvation effects on the pi*<--pi electronic transitions in simple aromatic
      chromophores: the role of the Slater-type Gaussian orbitals in the complete
      active space self-consistent field approach.
AB  - One of the most studied feature of aromatic molecular clusters in the gas phase
      is the shift of the pi*<--pi electronic transitions between the bare aromatic
      chromophore and its clusters. In the present ab initio complete active space self
      consistent field study the coupling of the basis set superposition error and
      counterpoise procedure and a combination of Pople- and Slater-type Gaussian basis
      sets has been proven to reproduce quantitatively the gas-phase experimental
      shifts. The quantal results are here analyzed with respect to the electrostatic
      and polarization forces and electron density differences, and connected with the
      sign of the shifts of the electronic transitions.

PMID- 16965067
TI  - D matrix analysis of the Renner-Teller effect: an accurate three-state
      diabatization for NH2.
AB  - Some time ago we published our first article on the Renner-Teller (RT) model to
      treat the electronic interaction for a triatomic molecule [J. Chem. Phys. 124,
      081106 (2006)]. The main purpose of that Communication was to suggest considering
      the RT phenomenon as a topological effect, just like the Jahn-Teller phenomenon.
      However, whereas in the first publication we just summarized a few basic features
      to support that idea, here in the present article, we extend the topological
      approach and show that all the expected features that characterize a three
      (multi) state RT-type'3 system of a triatomic molecule can be studied and
      analyzed within the framework of that approach. This, among other things, enables
      us to employ the topological D matrix [Phys. Rev. A 62, 032506 (2000)] to
      determine, a priori, under what conditions a three-state system can be
      diabatized. The theoretical presentation is accompanied by a detailed numerical
      study as carried out for the HNH system. The D-matrix analysis shows that the two
      original electronic states 2A1 and 2B1 (evolving from the collinear degenerate Pi
      doublet), frequently used to study this Renner-Teller-type system, are
      insufficient for diabatization. This is true, in particular, for the stable
      ground-state configurations of the HNH molecule. However, by including just one
      additional electronic state--a B state (originating from a collinear Sigma state)
      -it is found that a rigorous, meaningful three-state diabatization can be carried
      out for large regions of configuration space, particularly for those, near the
      stable configuration of NH2. This opens the way for an accurate study of this
      important molecule even where the electronic angular momentum deviates
      significantly from an integer value.

PMID- 16965068
TI  - Calculation of two-photon absorption spectra of donor-pi-acceptor compounds in
      solution using quadratic response time-dependent density functional theory.
AB  - Linear and quadratic response time-dependent density functional theories have
      been applied to calculate the photophysical properties of donor-pi-acceptor
      molecules which are known to have large nonlinear absorption. The linear
      absorption and two-photon absorption spectra predicted using hybrid functionals,
      including the Coulomb-attenuated model, with continuum solvation models are
      reported and compared to experiment and to previous theoretical predictions.
      While the quadratic response with these functionals overestimated the TPA cross
      sections relative to experiment when a Gaussian linewidth function was used, a
      fairly good agreement was obtained when a Lorentzian linewidth function was
      applied. In addition, the comparison of the TPA cross sections calculated by the
      sum over states with those calculated by the two-state approximation indicates
      the importance of the higher energy states in TPA, particularly in nondegenerate
      experiments.

PMID- 16965069
TI  - Simple method to obtain symmetry harmonics of point groups.
AB  - We propose a simple, self-consistent method to obtain basis functions of
      irreducible representations of a finite point group. Our method is based on
      eigenproblem formulation of a projection operator represented as a nonhomogeneous
      polynomial of angular momentum L. The method is shown to be more efficient than
      the usual numerical methods when applied to the analysis of high-order symmetry
      harmonics in cubic and icosahedral groups. For low-order symmetry harmonics the
      method provides rational coefficients of expansion in the Y(L,M) basis.

PMID- 16965070
TI  - Search for suitable approximation methods for fullerene structure and relative
      stability studies: case study with C50.
AB  - Local density approximation (LDA), several popular general gradient approximation
      (GGA), hybrid module based density functional theoretical methods: SVWN, BLYP,
      PBE, HCTH, B3LYP, PBE1PBE, B1LYP, and BHandHLYP, and some nonstandard hybrid
      methods are applied in geometry prediction for C60 and C70. HCTH with 3-21G basis
      set is found to be one of the best methods for fullerene structural prediction.
      In the predictions of relative stability of C50 isomers, PM3 is an efficient
      method in the first step for sorting out the most stable isomers. HCTH with 3-21G
      predicts very good geometries for C50, similar to the performance of B3LYP6
      31G(d). The gap between the highest occupied molecular orbital and the lowest
      unoccupied molecular orbital from the predictions of all the density functional
      theory methods has the following descending order: E(gap)(half-and-half
      hybrid)>E(gap)(B3LYP)>E(gap)(HCTH)(GGA)>E(gap)(SVWN)(LDA).

PMID- 16965071
TI  - A restricted-open-shell complete-basis-set model chemistry.
AB  - A restricted-open-shell model chemistry based on the complete basis set-quadratic
      Becke3 (CBS-QB3) model is formulated and denoted ROCBS-QB3. As the name implies,
      this method uses spin-restricted wave functions, both for the direct calculations
      of the various components of the electronic energy and for extrapolating the
      correlation energy to the complete-basis-set limit. These modifications eliminate
      the need for empirical corrections that are incorporated in standard CBS-QB3 to
      compensate for spin contamination when spin-unrestricted wave functions are used.
      We employ an initial test set of 19 severely spin-contaminated species including
      doublet radicals and both singlet and triplet biradicals. The mean absolute
      deviation (MAD) from experiment for the new ROCBS-QB3 model (3.6+/-1.5 kJ mol(
      1)) is slightly smaller than that of the standard unrestricted CBS-QB3 version
      (4.8+/-1.5 kJ mol(-1)) and substantially smaller than the MAD for the
      unrestricted CBS-QB3 before inclusion of the spin correction (16.1+/-1.5 kJ mol(
      1)). However, when applied to calculate the heats of formation at 298 K for the
      moderately spin-contaminated radicals in the G2/97 test set, ROCBS-QB3 does not
      perform quite as well as the standard unrestricted CBS-QB3, with a MAD from
      experiment of 3.8+/-1.6 kJ mol(-1) (compared with 2.9+/-1.6 kJ mol(-1) for
      standard CBS-QB3). ROCBS-QB3 performs marginally better than standard CBS-QB3 for
      the G2/97 set of ionization energies with a MAD of 4.1+/-0.1 kJ mol(-1) (compared
      with 4.4+/-0.1 kJ mol(-1)) and electron affinities with a MAD of 3.9+/-0.2 kJ
      mol(-1) (compared with 4.3+/-0.2 kJ mol(-1)), but the differences in MAD values
      are comparable to the experimental uncertainties. Our overall conclusion is that
      ROCBS-QB3 eliminates the spin correction in standard CBS-QB3 with no loss in
      accuracy.

PMID- 16965072
TI  - Calculation of interatomic decay widths of vacancy states delocalized due to
      inversion symmetry.
AB  - In a recent publication [J. Chem. Phys. 123, 204107 (2005)], we have introduced a
      new ab initio approach for the calculation of the widths of interatomic
      electronic decay of inner-shell vacancies in clusters. The new technique is based
      on the configuration interaction formalism first introduced for the description
      of resonance states by Fano [Phys. Rev. 124, 1866 (1961)] and on a Green function
      method for the description of the many-electron states involved in the electronic
      decay. Central to the new method is the selection of the physical excitation
      operators for the construction of the initial and final states of the interatomic
      decay. The previously described selection procedure has been formulated for
      localized vacancy states and runs into difficulties when applied to the decay of
      vacancy states delocalized due to inversion symmetry, e.g., (2s(-1)) 2Sigma(g,u)+
      states of Ne2+. Here we present a modified computational scheme suitable for
      interatomic decay of the energy-split gerade and ungerade states and apply it to
      the interatomic Coulombic decay in two homonuclear diatomic clusters: Ne2 and
      Ca2.

PMID- 16965073
TI  - A generalization of the charge equilibration method for nonmetallic materials.
AB  - Assigning effective atomic charges that properly reproduce the electrostatic
      fields of molecules is a crucial step in the construction of accurate interatomic
      potentials. We propose a new approach to calculate these charges, which as
      previous approaches are, is based on the idea of charge equilibration. However,
      we only allow charge to flow between covalently bonded neighbors by using the
      concept of so-called split charges. The semiempirical fit parameters in our
      approach do not only reflect atomic properties (electronegativity and atomic
      hardness) but also bond-dependent properties. The new method contains two popular
      but hitherto disjunct approaches as limiting cases. We apply our methodology to a
      set of molecules containing the elements silicon, carbon, oxygen, and hydrogen.
      Effective charges derived from electrostatic potential surfaces can be predicted
      more than twice as accurately as with previous works, at the expense of one
      additional fit parameter per bond type controlling the polarizability between two
      bonded atoms. Additional bond-type parameters can be introduced, but barely
      improve the results. An increase in accuracy of only 30% over existing techniques
      is achieved when predicting Mulliken charges. However, this could be improved
      with additional bond-type parameters.

PMID- 16965074
TI  - Ab initio study of the potential energy surface for the OH+CO-->H+CO2 reaction.
AB  - Potential energy surface for the reaction OH+CO-->H+CO2 has been calculated using
      the complete active space self-consistent-field and multireference configuration
      interaction methods with the correlation consistent triple-, quadruple-, and
      quintuple-zeta basis sets. A specific- reaction-parameters density functional
      theory has been suggested, in which the B3LYP functional is reoptimized to give
      the highly accurate potential energy surface with less computational efforts.

PMID- 16965075
TI  - A comparison of linear and nonlinear correlation factors for basis set limit
      Moller-Plesset second order binding energies and structures of He2, Be2, and Ne2.
AB  - The basis set limit Moller-Plesset second-order equilibrium bond lengths of He2,
      Be2, and Ne2, accurate to 0.01a0, are computed to be 5.785a0, 5.11a0, and 6.05a0.
      The corresponding binding energies are 22.4+/-0.1, 2180+/-20, and 86+/-2 muE(h),
      respectively. An accuracy of 95% in the binding energy requires an aug-cc-pV6Z
      basis or larger for conventional Moller-Plesset theory. This accuracy is obtained
      using an aug-cc-pV5Z basis if geminal basis functions with a linear correlation
      factor are included and with an aug-cc-pVQZ basis if the linear correlation
      factor is replaced by exp(-gammar(12)) with gamma=1. The correlation factor r(12)
      exp(-gammar(12)) does not perform as well, describing the atom more efficiently
      than the dimer. The geminal functions supplement the orbital basis in the
      description of both the short-range correlation, at electron coalescence, and the
      long-range dispersion correlation and the values of gamma that give the best
      binding energies are smaller than those that are optimum for the atom or the
      dimer. It is important to sufficiently reduce the error due to the resolution of
      the identity approximation for the three- and four-electron integrals and we
      recommend the complementary auxiliary basis set method. The effect of both
      orbital and geminal basis set superposition error must be considered to obtain
      accurate binding energies with small orbital basis sets. In this respect, we
      recommend using exp(-gammar(12)) with localized orbitals and the original orbital
      variant formalism.

PMID- 16965076
TI  - Multireference configuration interaction studies on the ground and excited states
      of N2O2: the potential energy curves of N2O2 along N-N distance.
AB  - In this paper, the ground and excited states of N2O2 were studied at the
      multireference configuration interaction (MRCI) level of theory with Dunning's
      [J. Chem. Phys. 90, 1007 (1985); 96, 6796 (1992)] correlation consistent basis
      sets augo-cc-pVDZ and aug-cc-pVTZ. The geometry optimizations were performed for
      the ground state of N2O2. The vertical excitation energies and transition moments
      were calculated for the low-lying singlet states of N2O2 including the lowest
      three 1A1 states, two 1B1 states, one 1B2 state, and two 1A2 states at the MRCI
      level of theory with Dunning's correlation consistent basis sets aug-cc-pVDZ, aug
      cc-pVTZ, and aug-cc-pVQZ. Furthermore, for the first time, the potential energy
      curves were calculated at the complete active space self-consistent-field and
      MRCI levels of theory for as many as 12 N2O2 singlet electronic states along the
      N-N distance. The dissociation asymptotes of these 12 N2O2 singlet electronic
      states were discussed.

PMID- 16965077
TI  - Isotope effects in the CO dimer: millimeter wave spectrum and rovibrational
      calculations of (12C18O)2.
AB  - The millimeter wave spectrum of the isotopically substituted CO dimer, (12C18O)2,
      was studied with the Orotron jet spectrometer, confirming and extending a
      previous infrared study [A. R. W. McKellar, J. Mol. Spectrosc. 226, 190 (2004)].
      A very dilute gas mixture of CO in Ne was used, which resulted in small
      consumption of 12C18O sample gas and produced cold and simple spectra. Using the
      technique of combination differences together with the data from the infrared
      work, six transitions in the 84-127 GHz region have been assigned. They belong to
      two branches, which connect four low levels of A+ symmetry to three previously
      unknown levels of A- symmetry. The discovery of the lowest state of A- symmetry,
      which corresponds to the projection K=0 of the total angular momentum J onto the
      intermolecular axis, identifies the geared bending mode of the 12C18O dimer at
      3.607 cm(-1). Accompanying rovibrational calculations using a recently developed
      hybrid potential from ab initio coupled cluster [CCSD(T)] and symmetry-adapted
      perturbation theory calculations [G. W. M. Vissers et al., J. Chem. Phys. 122,
      054306 (2005)] gave very good agreement with experiment. The isotopic dependence
      of the A+/A- energy splitting, the intermolecular separation R, and the energy
      difference of two ground state isomers, which change significantly when 18O or
      13C are substituted into the normal (12C16O)2 isotopolog [L. A. Surin et al., J.
      Mol. Spectrosc. 223, 132 (2004)], was explained by these calculations. It turns
      out that the change in anisotropy of the intermolecular potential with respect to
      the shifted monomer centers of mass is particularly significant.

PMID- 16965078
TI  - Electronic spectroscopy of the A1A" <--> X1A' system of CDBr.
AB  - We report fluorescence excitation and single vibronic level emission spectra of
      jet-cooled CDBr in the 450-750 nm region. A total of 32 cold bands involving the
      pure bending levels 2(0)n with n=3-10 and combination bands 2(0)n3(0)1 (n=2-10),
      2(0)n3(0)2 (n=2-9), 1(0)(1)2(0)n (n=7-10), and 1(0)(1)2(0)n3(0)(1) (n=6,8-9) in
      the A1A" <-- X1A' system of this carbene were observed; most of these are
      reported and/or rotationally analyzed here for the first time. Rotational
      analysis yielded band origins and effective (B) rotational constants for both
      bromine isotopomers (CD79Br and CD81Br). The derived A1A" vibrational intervals
      are combined with results of Yu et al. [J. Chem. Phys. 115, 5433 (2001)] to
      derive barriers to linearity for the 2n, 2n3(1), and 2n3(2) progressions. The
      A1A" state C-D stretching frequency (2350 cm(-1)) is determined for the first
      time, in excellent agreement with theory, as are the 79Br-81Br isotope splittings
      in the excited state. Our emission spectra probe the vibrational structure of the
      X1A' and a3A" states up to approximately 9000 cm(-1) above the vibrationless
      level of the X1A' state; the total number of levels observed is around twice that
      previously reported. Unlike CHBr, where even the lowest bending levels are
      perturbed by spin-orbit interaction with the triplet origin, the term energy of
      every level save one below 3000 cm(-1) in CDBr is reproduced by a Dunham
      expansion to within a standard deviation of 1 cm(-1), and a spin-orbit coupling
      matrix element of approximately 330 cm(-1) is derived from a deperturbation
      analysis of the triplet origin. The multireference configuration interaction
      (MRCI) calculations of Yu et al. [J. Chem. Phys. 115, 5433 (2001)] well reproduce
      triplet perturbations in the pure bending manifold, and globally, the vibrational
      frequencies of X1A', a3A", and A1A" are in excellent agreement with theoretical
      predictions.

PMID- 16965079
TI  - Application of density functional theory for studies of excited states and
      phosphorescence of platinum(II) acetylides.
AB  - The electronic states of different conformations of platinum acetylides
      Pt(PH3)2(C[triple bond]C-Ph)2 and Pt(PH3)2(C[triple bond]C-PhC[triple bond]C-Ph)2
      (PE1 and PE2) were calculated with density functional theory (DFT) using
      effective core potential basis sets. Time dependent DFT calculations of UV
      absorption spectra showed strong dependence of the intense absorption band maxima
      on mutual orientation of the phenyl rings with respect to the P-Pt-P axis.
      Geometry optimization of the first excited triplet state (T1) indicates broken
      symmetry structure with the excitation being localized in one ligand. This splits
      the two substitution ligands into a nondistorted aromatic ring with the C[triple
      bond]C-Ph bonds for one side and into a quinoid structure with a cumulenic C=C=C
      link on the other side. Quadratic response (QR) calculations of spin-orbit
      coupling and phosphorescence radiative lifetime (tauR) indicated a good agreement
      with experimental tauR values reported for solid PE1 and PE2 and PE2 capped with
      dendrimers in tetrahydrofuran solutions. The QR calculations reproduced an
      increase of tauR upon prolongation of pi chain of ligands and concommittant
      redshift of the phosphorescence. Moreover, it is shown how the phosphorescence
      borrows intensity from sigma-->pi* transitions localized at the C[triple bond]C
      Pt-P fragments and that there is no intensity borrowing from delocalized pi-->pi*
      transitions.

PMID- 16965080
TI  - Infrared spectra of HC2-.(C2H2)n and O2-.(C2H2)n clusters (n=2-5).
AB  - We study the solvation of HC2- and O2- with acetylene ligands by means of
      midinfrared photodissociation spectroscopy in the CH stretching region,
      monitoring C2H2 evaporation upon infrared photon absorption by the parent cluster
      ions. Our findings are interpreted with the help of density functional theory.
      The infrared spectra indicate that while the binding generally occurs through
      ionic H bonds, there are two different classes of ligands which differ in their
      binding strength. This holds true for both core ions, even though their
      electronic structures and charge distributions are very different.

PMID- 16965081
TI  - Gas phase electronic spectra of the carbon chains C5, C6, C8, and C9.
AB  - Three electronic absorption systems for C5 at 511, 445, and 232 nm and one for
      C6, C8, and C9 centered at 228, 259, and 288 nm have been observed in the gas
      phase. The C5 chain was produced in both discharge and ablation sources and
      detected using resonant two-color two-photon ionization spectroscopy involving
      10.5 eV photons. The decay of the excited singlet electronic states indicates
      fast intramolecular processes on a subpicosecond time scale. The internal energy
      is assumed to be trapped in a triplet state for at least 15 micros. Hole-burning
      experiments on the 2 (3)Sigma(u)- <-- X (3)Sigma(g)- transition of C6, C8, and
      (1)Sigma(u)+ <-- X (1)Sigma(g)+ of C9 confirm the predissociative nature of the
      excited electronic states.

PMID- 16965082
TI  - Photodissociation of Mg+-XCH3 (X=F, Cl, Br, and I) complexes. I. Electronic
      spectra and dissociation pathways.
AB  - Photodissociation spectra of Mg+-XCH3 (X=F, Cl, Br, and I) complexes have been
      measured in the ultraviolet region (225-415 nm). Several fragment ions with and
      without charge transfer (CT), Mg+, XCH3+, MgX+, MgCH3+, CH3+, and X+, were formed
      by evaporation (intermolecular bond dissociation) and intracluster reaction
      (intramolecular bond dissociation) via excited electronic states. Branching
      ratios of these ions were found to depend both on absorption bands and on halogen
      atoms. The ground states of the complexes were calculated to have geometries in
      which the Mg atom lies next to X atom of methyl halide molecules. Positive
      charges of the complexes are confirmed to be almost localized on Mg. Observed
      absorption bands were assigned to the transitions of the Mg+2P-2S atomic line
      perturbed by interactions with methyl halide molecules. Branching ratios of
      fragment ions can be partly explained by the stability of fragment ions and
      neutral counterparts. From the excited state potential energy curves along the Mg
      X bond distance, dissociation reaction after CT was concluded to proceed
      predissociatively; potential curve crossings between the initially excited states
      and repulsive CT states may have a crucial role in the formation of CH3+, XCH3+,
      and X+. In particular, XCH3+ ions were formed via repulsive CT states having a
      character of electron excitation from Xnp to Mg+3s.

PMID- 16965083
TI  - Photodissociation of Mg+-XCH3 (X=F, Cl, Br, and I) complexes. II. Fragment
      angular and energy distributions.
AB  - Angular and energy distributions of photofragments from Mg+-XCH3 (X=F, Cl, Br,
      and I) were deduced from time-of-flight (TOF) profiles measured by rotating the
      polarization direction of the dissociation laser with respect to ion beam
      direction. The TOF profiles of ICH3+ and MgI+ fragment ions produced from Mg+
      ICH3 complex with 266 and 355 nm photons showed clear but opposite recoil
      anisotropy to each other. In addition, BrCH3+ formed by a dissociation of the Mg+
      BrCH3 complex at a photolysis wavelength of 266 nm also showed an anisotropic
      distribution in the TOF profile which had the same behavior as the profile of
      ICH3+. For Mg+-FCH3 complex, CH3+ and MgF+ formed with a 266 nm photon had also
      spatial anisotropy, in which the TOF profile of MgF+ was almost opposite to that
      of MgI+. These anisotropic distributions were explained by (1) local excitation
      on the Mg+ ion, (2) rapid dissociation compared with a rotational period of the
      parent complex, and (3) geometrical structures of the parent complexes.
      Anisotropy beta parameter values were determined to be +1.30(ICH3+), -0.50(MgI+),
      +0.74(BrCH3+), and +0.75(CH3+ and MgF+). This dependence on the halogen atom
      observed in beta values was qualitatively explained by both the geometrical
      parameters and classical rotational periods of parent complexes. In the product
      energy distribution, 46%, 40%, 21%, 16%, and 16% of available energies were found
      to be transferred into translational energies of ICH3+, MgI+, BrCH3 +, CH3+, and
      MgF+, respectively. These values were compared with energy distributions
      estimated by a statistical prior distribution and a nonstatistical impulsive
      model. For ICH3+ and MgI+, the translational energies determined from the
      measurement had values between those estimated from statistical and
      nonstatistical models. On the other hand, the energy partitioning for the product
      ions of BrCH3+, CH3+, and MgF+ was found to be almost statistical. From these
      considerations, we concluded that nonstatistical processes were more important in
      the dissociation of Mg+-ICH3 than in other systems.

PMID- 16965084
TI  - Calculating vibrational energies and wave functions of vinylidene using a
      contracted basis with a locally reorthogonalized coupled two-term Lanczos
      eigensolver.
AB  - We use a contracted basis+Lanczos eigensolver approach to compute vinylidene-like
      vibrational states of the acetylene-vinylidene system. To overcome problems
      caused by loss of orthogonality of the Lanczos vectors we reorthogonalize Lanczos
      vector and use a coupled two-term approach. The calculations are done in CC-HH
      diatom-diatom Jacobi coordinates which make it easy to compute states one
      irreducible representation at a time. The most costly parts of the calculation
      are parallelized and scale well. We estimate that the vinylidene energies we
      compute are converged to approximately 1 cm(-1).

PMID- 16965085
TI  - Intermolecular potentials of the methane dimer calculated with Moller-Plesset
      perturbation theory and density functional theory.
AB  - We have calculated the intermolecular interaction potentials of the methane dimer
      at the minimum-energy D(3d) conformation using the Hartree-Fock (HF) self
      consistent theory, the correlation-corrected second-order Moller-Plesset (MP2)
      perturbation theory, and the density functional theory (DFT) with the Perdew-Wang
      (PW91) functional as the exchange or the correlation part. The HF calculations
      yield unbound potentials largely due to the exchange-repulsion interaction. In
      the MP2 calculations, the basis set effects on the repulsion exponent, the
      equilibrium bond length, the binding energy, and the asymptotic behavior of the
      calculated intermolecular potentials have been thoroughly studied. We have
      employed basis sets from the Slater-type orbitals fitted with Gaussian functions
      (STO-nG) (n=3-6) [Quantum Theory of Molecular and Solids: The Self-Consistent
      Field for Molecular and Solids (McGraw-Hill, New York, 1974), Vol. 4], Pople's
      medium size basis sets of Krishnan et al. [J. Chem. Phys. 72, 650 (1980)] [up to
      6-311++G(3df,3pd)] to Dunning's correlation consistent basis sets [J. Chem. Phys.
      90, 1007 (1989)] (cc-pVXZ and aug-cc-pVXZ) (X=D, T, and Q). With increasing basis
      size, the repulsion exponent and the equilibrium bond length converge at the 6
      31G** basis set and the 6-311++G(2d,2p) basis set, respectively, while a large
      basis set (aug-cc-pVTZ) is required to converge the binding energy at a chemical
      accuracy (approximately 0.01 kcal/mol). Up to the largest basis set used, the
      asymptotic dispersion coefficient has not converged to the destined C6 value from
      molecular polarizability calculations. The slow convergence could indicate the
      inefficacy of using the MP2 calculations with Gaussian-type functions to model
      the asymptotic behavior. Both the basis set superposition error (BSSE) corrected
      and uncorrected results are presented to emphasize the importance of including
      such corrections. Only the BSSE corrected results systematically converge to the
      destined potential curve with increasing basis size. The DFT calculations
      generate a wide range of interaction patterns, from purely unbound to strongly
      bound, underestimating or overestimating the binding energy. The binding energy
      calculated using the PW91PW91 functional and the equilibrium bond length
      calculated using the PW91VP86 functional are close to the MP2 results at the
      basis set limit.

PMID- 16965086
TI  - A comparison of rigid and flexible water models in collisions of monomers and
      small clusters.
AB  - In this study we have investigated the dynamics of small water clusters using
      microcanonical molecular dynamics simulations. The clusters are formed by
      colliding vapor monomers with target clusters of two and five molecules. The
      monomers are sampled from a thermal ensemble at T=300 K and target clusters with
      several total energies are considered. We compare rigid extended simple point
      charge water with flexible counterparts having intramolecular harmonic bonds with
      force constants 10(3) and 10(5) kcal(mol A2). We show that the lifetimes of the
      clusters formed via collision process are similar for the rigid model and the
      flexible model with the bigger force constant, if the translational temperatures
      of the target cluster molecules are equal. The model with the smaller force
      constant results in much longer lifetimes due to the stabilizing effect caused by
      the kinetic energy transfer into internal vibration of the molecules. This
      process may take several hundreds of picoseconds, giving rise to time-dependent
      decay rates of constant-energy clusters. A study of binary collisions of water
      molecules shows that the introduction of flexibility to the molecules increases
      the possibility of dimer formation and thus offers an alternative route for dimer
      production in vapors. Our results imply that allowing for internal degrees of
      freedom is likely to enhance gas-liquid nucleation rates in water simulations.

PMID- 16965087
TI  - A detailed quantum mechanical and quasiclassical trajectory study on the dynamics
      of the H+ + H2 --> H2 + H+ exchange reaction.
AB  - The H+ + H2 exchange reaction has been studied theoretically by means of a
      different variety of methods as an exact time independent quantum mechanical,
      approximate quantum wave packet, statistical quantum, and quasiclassical
      trajectory approaches. Total and state-to-state reaction probabilities in terms
      of the collision energy for different values of the total angular momentum
      obtained with these methods are compared. The dynamics of the reaction is
      extensively studied at the collision energy of E(coll)=0.44 eV. Integral and
      differential cross sections and opacity functions at this collision energy have
      been calculated. In particular, the fairly good description of the exact quantum
      results provided by the statistical quantum method suggests that the dynamics of
      the process is governed by an insertion mechanism with the formation of a long
      lived collision complex.

PMID- 16965088
TI  - Coherent control of collision processes: Penning versus associative ionization.
AB  - Coherent control theory is applied to the control of Ne*(3s,(3)P2)+Ar((1)S0)
      collisions and computations are shown that display extensive control over these
      processes. Indeed we demonstrate that it is possible to essentially turn on and
      off the cross sections for both the Penning and associative ionization processes.
      This facility arises from the interference between matter waves induced by
      creating a linear superposition of the degenerate M={-2,-1,0,1,2} Zeeman
      sublevels of the Ne*(3s,(3)P2) target atom. The computations, conducted at
      collision energies in the 1-8 kcal/mole range, are based on combining, within the
      "rotating atom approximation," empirically derived and ab initio ionization
      widths.

PMID- 16965089
TI  - High resolution spectra and conformational analysis of 2-butoxy radical.
AB  - We have recorded five high resolution (200 MHz), rotationally resolved,
      vibrational bands of the B-X electronic transition of 2-butoxy. Two bands of the
      2-butoxy spectrum have been rotationally analyzed and assigned to two different
      geometrical conformers of the molecule. The analyses allow the determination of
      the six experimental rotational constants defined by the geometry of the species
      in the ground (X) and excited (B) electronic states and also four spin-rotation
      constants for the X electronic state of the conformers. Comparison of the
      experimental rotational constants with the results of ab initio computations
      provides unambiguous conformational assignment of these bands. This approach can
      be extended to assign two other spectral bands to the third 2-butoxy conformer.

PMID- 16965090
TI  - Exact density functionals for two-electron systems in an external magnetic field.
AB  - In principle, the extension of density functional theory (DFT) to Coulombic
      systems in a nonvanishing magnetic field is via current DFT (CDFT). Though CDFT
      is long established formally, relatively little is known with respect to any
      generally applicable, reliable approximate E(XC) and A(XC) functionals analogous
      with the workhorse approximate functionals (local density approximation and
      generalized gradient approximation) of ordinary DFT. Progress can be aided by
      having benchmark studies on a solvable correlated system. At zero field, the best
      known finite system for such purposes is Hooke's atom. Recently we extended the
      exact ground state solutions for this two-electron system to certain combinations
      of nonzero external magnetic fields and confinement strengths. From those exact
      solutions, as well as high-accuracy numerical results for other field and
      confinement combinations, we construct the correlated electron density and
      paramagnetic current density, the exact Kohn-Sham orbitals, and the exact DFT and
      CDFT exchange-correlation energies and potentials. We compare with results from
      several widely used approximate functionals, all of which exhibit major
      qualitative failures, whether in CDFT or in naive application of ordinary DFT. We
      also illustrate how the CDFT vorticity variable nu is a computationally difficult
      quantity which may not be appropriate in practice to describe the external B
      field effects on E(XC) and A(XC).

PMID- 16965091
TI  - Glass transition in pure and doped amorphous solid water: an ultrafast
      microcalorimetry study.
AB  - Using an ultrafast scanning microcalorimetry apparatus capable of heating rates
      in excess of 10(5) Ks, we have conducted the first direct measurements of
      thermodynamic properties of pure and doped amorphous solid water (also referred
      to as low density amorphous ice) in the temperature range from 120 to 230 K.
      Ultrafast microcalorimetry experiments show that the heat capacity of pure
      amorphous solid water (ASW) remains indistinguishable from that of crystalline
      ice during rapid heating up to a temperature of 205+/-5 K where the ASW undergoes
      rapid crystallization. Based on these observations, we conclude that the enthalpy
      relaxation time in pure ASW must be greater than 10(-5) s at 205 K. We argue that
      this result contradicts the assignment of glass transition temperature to 135 K
      and that ASW may undergo fragile to strong transition at temperatures greater
      than 205 K. Unlike pure ASW, we observe an approximately twofold rise in heat
      capacity of CH3COOH doped ASW at 177+/-5 K. We discuss results of past studies
      taking into account possible influence of impurities and confinement on physical
      properties of ASW.

PMID- 16965092
TI  - Gas-liquid phase separation in oppositely charged colloids: stability and
      interfacial tension.
AB  - We study the phase behavior and the interfacial tension of the screened Coulomb
      (Yukawa) restricted primitive model (YRPM) of oppositely charged hard spheres
      with diameter sigma using Monte Carlo simulations. We determine the gas-liquid
      and gas-solid phase transitions using free energy calculations and grand
      canonical Monte Carlo simulations for varying inverse Debye screening length
      kappa. We find that the gas-liquid phase separation is stable for
      kappasigma<or=4, and that the critical temperature decreases upon increasing the
      screening of the interaction (decreasing the range of the interaction). In
      addition, we determine the gas-liquid interfacial tension using grand-canonical
      Monte Carlo simulations. The interfacial tension decreases upon increasing the
      range of the interaction. In particular, we find that simple scaling can be used
      to relate the interfacial tension of the YRPM to that of the restricted primitive
      model, where particles interact with bare Coulomb interactions.

PMID- 16965093
TI  - Hydrogen bonding in liquid and supercritical 1-octanol and 2-octanol assessed by
      near and midinfrared spectroscopy.
AB  - The near and midinfrared spectra of 1-octanol (and 2-octanol) have been measured
      along the liquid-gas coexistence curve from room temperature up to the critical
      point and in the supercritical domain along the isotherm T=385 degrees C (and
      T=365 degrees C) above the critical point of both 1-octanol and 2-octanol for
      pressure ranging from 0.5 up to 15 MPa. The density values of SC 1- and 2-octanol
      have been estimated by analysing the near infrared (NIR) spectra in the
      3nu(a)(CH) region. A quantitative analysis of the absorption band associated with
      the OH stretching vibration [nu(OH)] and its first and second overtones [2nu(OH)
      and 3nu(OH)] was carried out in order to estimate the percentage of "free" OH
      groups in both alcohols in the whole thermodynamic domain investigated here. Very
      consistent results have been obtained from the independent analysis of these
      three different absorption bands which gave us a good confidence in the degree of
      hydrogen bonding reported here for 1- and 2-octanol. Thus, the percentage of free
      OH groups which is around 5% in liquid 1-octanol under ambient conditions
      strongly increase up to 70%-80% at a temperature of about 340 degrees C. Then, in
      the supercritical domain, upon a decrease of the density from 0.4 to 0.1 g cm(
      3), the fraction of free hydroxyl groups is nearly constant presenting a
      plateaulike regime around 80%. As the density decreases again, this plateau
      regime is followed by a further increase of X(nb) which reaches a value of 96%
      for the system in the gaseous phase (0.01 g cm(-3); P=0.45 MPa). Finally, it
      comes out from this study that the percentage of free OH groups is always greater
      in 2-octanol than in 1-octanol at the same density.

PMID- 16965095
TI  - Freezing-in and production of entropy in vitrification.
AB  - Following the classical concepts developed by Simon [Z. Anorg. Allg. Chem. 203,
      219 (1931)], vitrification in the cooling of glass-forming melts is commonly
      interpreted as the transformation of a thermodynamically (meta)stable equilibrium
      system into a frozen-in, thermodynamically nonequilibrium system, the glass.
      Hereby it is assumed that the transformation takes place at some well-defined
      sharp temperature, the glass transition temperature Tg. However, a more detailed
      experimental and theoretical analysis shows that the transition to a glass
      proceeds in a broader temperature range, where the characteristic times of change
      of temperature, tauT=-(TT), and relaxation times, tau, of the system to the
      respective equilibrium states are of similar order of magnitude. In this
      transition interval, the interplay of relaxation and change of external control
      parameters determines the value of the structural order parameters. In addition,
      irreversible processes take place in the transition interval, resulting both in
      an entropy freezing-in as well as in an irreversible increase of entropy and, as
      a result, in significant changes of all other thermodynamic parameters of the
      vitrifying systems. The effect of entropy production on glass transition and on
      the properties of glasses is analyzed here for the first time. In this analysis,
      the structural order-parameter concept as developed by de Donder and van
      Rysselberghe [Thermodynamic Theory of Affinity (Stanford University Press,
      Stanford, 1936)] and Prigogine and Defay [Chemical Thermodynamics (Longmans,
      London, 1954)] is employed. In the framework of this approach we obtain general
      expressions for the thermodynamic properties of vitrifying systems such as heat
      capacity, enthalpy, entropy, and Gibbs' free energy, and for the entropy
      production. As one of the general conclusions we show that entropy production has
      a single maximum upon cooling and two maxima upon heating in the glass transition
      interval. The theoretical concepts developed allow us to explain in addition to
      the thermodynamic parameters also specific features of the kinetic parameters of
      glass-forming melts such as the viscosity. Experimental results are presented
      which confirm the theoretical conclusions. Further experiments are suggested,
      allowing one to test several additional predictions of the theory.

PMID- 16965094
TI  - Radiation damage to DNA: electron scattering from the backbone subunits.
AB  - In the context of damage to DNA by low energy electrons, we carry out
      calculations of electron scattering from tetrahydrofuran and phosphoric acid,
      models of the subunits in the DNA backbone, as a first step in simulating the
      electron capture process that occurs in the cell. In the case of tetrahydrofuran,
      we also compare with previous theoretical and experimental data. A comparison of
      the shape of the resonant structures to virtual orbitals is also performed to
      gain insight into the systematic connections with electron scattering from
      similar molecules and dissociative electron attachment experiments.

PMID- 16965096
TI  - Structure change of liquid GaSb under pressure: an ab initio molecular-dynamics
      simulation.
AB  - We have performed ab initio molecular-dynamics simulation of liquid GaSb (l-GaSb)
      up to 20.0 GPa. The calculated structure factors are consistent with the recent
      experimental results, and the partial structure parameters show that the
      structure of l-GaSb under pressure contracts nonuniformly. In the whole
      calculated pressure region, the contraction of l-GaSb can be divided into three
      substages: 1.8-5.4, 5.4-10.0, and 10.0-20.0 GPa. It is further confirmed by
      analyzing the bond-angle distributions of Ga-Ga-Ga and Sb-Sb-Sb that the
      rearrangement of Sb atoms under pressure plays a crucial role in the structure
      change of l-GaSb.

PMID- 16965097
TI  - Hydration and contact ion pairing of Ca2+ with Cl- in supercritical aqueous
      solution.
AB  - X-ray absorption fine structure (XAFS) spectroscopy was used to measure the first
      shell structure about Ca2+ in high-temperature aqueous solution. XAFS spectra
      were acquired at the Ca K edge at temperatures up to 400 degrees C and pressures
      up to 350 bars. For the system at 400 degrees C, both Ca (4038.5 eV) and Cl
      (2822.4 eV) K-edge data were acquired and a global model was used to fit the two
      independent sets of XAFS data. Measurements were made at the bending magnet
      beamline (sector 20) at the Advanced Photon Source, Argonne. Above 250 degrees C,
      a significant number of Ca2+-Cl- direct contact ion pairs form in agreement with
      existing thermodynamic data for this system. For a 1 m CaCl2 solution at 400
      degrees C, the mean coordination structure about Ca2+ contains 3.2+/-0.6 water
      molecules at an average Ca-O distance of 2.356+/-0.026 A and 1.8+/-0.7 Cl- at a
      Ca-Cl distance of 2.677+/-0.007 A. An evaluation of the Ca and Cl preedge and
      near-edge (x-ray absorption structure) spectra provided further confirmation of
      the change in the Ca2+ first-shell structure and symmetry. Overall these
      measurements provide a structural basis for understanding solvation of Ca2+ in
      hydrothermal systems. These results also provide important new insights into the
      structural aspects of Ca2+ ion pairing that are the basis of many biological
      processes under ambient conditions.

PMID- 16965098
TI  - Three-dimensional square water in the presence of an external electric field.
AB  - In this work we study a tridimensional statistical model for the hydrogen-bond
      (HB) network formed in liquid water in the presence of an external electric
      field. This model is analogous to the so-called square water, whose ground state
      gives a good estimate for the residual entropy of the ice. In our case, each
      water molecule occupies one site of a cubic lattice, and no hole is allowed. The
      hydrogen atoms of water molecules are disposed at the lines connecting nearest
      neighbor sites, in a way that each water can be found in 15 different states. We
      say that there is a hydrogen bond between two neighboring molecules when only one
      hydrogen is in the line connecting both molecules. Through Monte Carlo
      simulations with Metropolis and entropic sampling algorithms, and by exact
      calculations for small lattices, we determined the dependence of the number of
      molecules aligned to the field and the number of hydrogen bonds per molecule as a
      function of temperature and the intensity of the external field. The results for
      both approaches showed that, different of the two-dimensional case, there is no
      maximum in the number of HBs as a function of the electric field. However, we
      observed nonmonotonic behaviors as a function of the temperature of the
      quantities of interest. We also found the dependence of the entropy on the
      external electric field at very low temperatures. In this case, the entropy
      vanishes for the value of the external field for which the contributions to the
      total energy coming from the HBs and the field become the same.

PMID- 16965099
TI  - Initial oxidation of the Rh(110) surface: ordered adsorption and surface oxide
      structures.
AB  - The initial oxidation of the Rh(110) surface was studied by scanning tunneling
      microscopy, core level spectroscopy, and density functional theory. The
      experiments were carried out exposing the Rh(110) surface to molecular or atomic
      oxygen at temperatures in the 500-700 K range. In molecular oxygen ambient, the
      oxidation terminates at oxygen coverage close to a monolayer with the formation
      of alternating islands of the (10x2) one-dimensional surface oxide and (2x1)p2mg
      adsorption phases. The use of atomic oxygen facilitates further oxidation until a
      structure with a c(2x4) periodicity develops. The experimental and theoretical
      results reveal that the c(2x4) structure is a "surface oxide" very similar to the
      hexagonal O-Rh-O trilayer structures formed on the Rh(111) and Rh(100)
      substrates. Some of the experimentally found adsorption phases appear unstable in
      the phase diagram predicted by thermodynamics, which might reflect kinetic
      hindrance. The structural details, core level spectra, and stability of the
      surface oxides formed on the three basal planes are compared with those of the
      bulk RhO2 and Rh2O3.

PMID- 16965100
TI  - Near homogeneous variation of potentials in large systems and the electronic
      structure of molecular quantum dots.
AB  - It is shown from Kohn-Sham (KS) density-functional theory that in a large
      molecular system, the Coulomb potential, molecular electrostatic potential, and
      KS effective potential may exhibit an approximately homogeneous variation in
      space, in response to a small change of the electron number. The homogeneous
      variation of potentials underlies the constant interaction (CI) model of quantum
      dots (QDs) and is related to the delocalization and invariance of KS orbitals,
      the identical shift of KS levels, and a natural definition of the QD capacitance.
      Calculation results of a fullerene C60 and a single-walled carbon nanotube are
      presented. Although the homogeneity of the potential variation is not perfect, it
      seems to lead to fairly good approximation of the CI model to the addition energy
      spectra of these systems.

PMID- 16965101
TI  - Growth and decomposition of aligned and ordered PdO nanoparticles.
AB  - The formation, thermal decomposition, and reduction of small PdO particles were
      studied by high-resolution transmission electron microscopy and selected area
      electron diffraction. Well-defined Pd particles (mean size of 5-7 nm) were grown
      epitaxially on NaCl (001) surfaces and subsequently covered by a layer of
      amorphous SiO2 (25 nm), prepared by reactive deposition of SiO in 10(-2) Pa O2.
      The resulting films were exposed to molecular O2 in the temperature range of 373
      673 K, and the growth of PdO was studied. The formation of a PdO phase starts at
      623 K and is almost completed at 673 K. The high-resolution experiments suggest a
      topotactic growth of PdO crystallites on top of the original Pd particles.
      Subsequent reaction of the PdO in 10 mbar CO for 15 min and thermal decomposition
      in 1 bar He for 1 h were also investigated in the temperature range from 373 to
      573 K. Reductive treatments in CO up to 493 K do not cause a significant change
      in the PdO structure. The reduction of PdO starts at 503 K and is completed at
      523 K. In contrast, PdO decomposes in 1 bar He at around 573 K. The mechanism of
      PdO growth and decay is discussed and compared to results of previous studies on
      other metals, e.g., on rhodium.

PMID- 16965102
TI  - Electron stimulated desorption of anionic fragments from films of pure and
      electron-irradiated thiophene.
AB  - The electron stimulated desorption (ESD) of anions is used to explore the effects
      of electron irradiation on a thiophene film and we report measurements for
      electron impact on multilayer thiophene condensed on a polycrystalline platinum
      substrate. Below 22 eV and at low electron dose, desorbed anions include H- (the
      dominant signal) as well as S-, CH2-, SH- and SCH2-. Yield functions show that
      anions are desorbed both by dissociative electron attachment (DEA) with
      resonances observed at 9.5, 11, and 16 eV, and for energies >13 eV, by dipolar
      dissociation (DD). An increase in the S- signal from electron irradiated (beam
      damaged) thiophene films and the appearance of a new DEA resonance in the S-
      yield function at 6 eV are linked to rupture of the thiophene ring and the
      formation of sulfur-terminated products within the film. The threshold energy for
      ring rupture is 5 eV. The desorption of new anions such as C4H3S- (Thiophene-H)-
      is also observed from electron irradiated films and these likely arise from the
      decomposition of large radiation product molecules synthesized in the film. The
      yield functions of H-, S-, SH-, (Thiophene-H)-, and (Thiophene+H)- anions from
      irradiated thiophene films that have been annealed to 300 K, each exhibit a
      single resonant feature centered around 5.1 eV, suggesting that all signals
      derive from DEA to the same molecular radiation product. In contrast, only H- and
      S- are observed to desorb from films of 2-2-bithiophene and no resonance is seen
      below approximately 10 eV in the anion yield functions. These data suggest that
      electron irradiation causes formation of ring-opened oligomers, and that closed
      ring or 'classical" oligomers, (similar to bithiophene) if formed, contribute
      little to the ESD of anions.

PMID- 16965103
TI  - Self-catalysis: a contamination-free, substrate-free growth mechanism for single
      crystal nanowire and nanotube growth by chemical vapor deposition.
AB  - A unified mechanism for the growth of a wide variety of long, uniform, single
      crystal nanowires and whiskers, including III-V and II-VI binary, ternary, and
      quaternary nanowires and whiskers, without the use of any substrate and catalyst
      has been presented. While elucidating the mechanism, attempts have been made to
      provide a kinetic and thermodynamic rationale for the growth. Various features of
      the growth mechanism, including the formation of liquid droplets and seeds,
      nucleation, and creation of products, have been discussed. Extensive studies of
      illustrative examples provide the validity of the proposed mechanism. The
      influence of various parameters such as growth temperature and chamber pressure
      on the growth mechanism has been studied. The advantages and disadvantages of the
      proposed mechanism, and its superiority to the well-known vapor-liquid-solid
      mechanism, have been elucidated. Means to improve the mechanism to obtain self
      aligned nanowires and whiskers have been suggested. Based on these, it has been
      demonstrated that the present mechanism is indeed a powerful self-catalytic
      growth mechanism uniquely suited to the growth of a wide variety of single
      crystal nanowires and whiskers. It can be very useful also for the growth of
      single-crystal nanotubes.

PMID- 16965104
TI  - N doping of TiO2(110): photoemission and density-functional studies.
AB  - The electronic properties of N-doped rutile TiO2(110) have been investigated
      using synchrotron-based photoemission and density-functional calculations. The
      doping via N2+ ion bombardment leads to the implantation of N atoms
      (approximately 5% saturation concentration) that coexist with O vacancies. Ti 2p
      core level spectra show the formation of Ti3+ and a second partially reduced Ti
      species with oxidation states between +4 and +3. The valence region of the TiO(2
      x)N(y)(110) systems exhibits a broad peak for Ti3+ near the Fermi level and N
      induced features above the O 2p valence band that shift the edge up by
      approximately 0.5 eV. The magnitude of this shift is consistent with the
      "redshift" observed in the ultraviolet spectrum of N-doped TiO2. The experimental
      and theoretical results show the existence of attractive interactions between the
      dopant and O vacancies. First, the presence of N embedded in the surface layer
      reduces the formation energy of O vacancies. Second, the existence of O vacancies
      stabilizes the N impurities with respect to N2(g) formation. When oxygen
      vacancies and N impurities are together there is an electron transfer from the
      higher energy 3d band of Ti3+ to the lower energy 2p band of the N(2-)
      impurities.

PMID- 16965105
TI  - Superficial segregation in nanoparticles: from facets to infinite surfaces.
AB  - We compare the superficial segregations of the Cu-Ag system for a nanoparticle
      and for surfaces that are structurally equivalent to each of its facet. Based on
      a lattice-gas model and within a mean-field formalism, we derive segregation
      isotherms at various temperatures in the canonical ensemble, i.e., for a given
      overall solute concentration, and in the semigrand canonical ensemble, i.e., for
      a given bulk solute concentration. If both processes are very similar for high
      temperatures, they differ substantially at lower temperatures. Due to the finite
      size effect and the indirect coupling between facets and edges, the relative
      position of the phase transitions of the facets and the corresponding surfaces is
      inversed when displayed as a function of the solute bulk concentration. Moreover,
      we show that working in the semigrand canonical ensemble is a much more efficient
      way to study this phenomenon, although nanoparticles are "canonical" objects in
      essence.

PMID- 16965106
TI  - Friction laws for lubricated nanocontacts.
AB  - We have used friction force microscopy to probe friction laws for nanoasperities
      sliding on atomically flat substrates under controlled atmosphere and liquid
      environment, respectively. A power law relates friction force and normal load in
      dry air, whereas a linear relationship, i.e., Amontons' law, is observed for
      junctions fully immersed in model lubricants, namely,
      octamethylciclotetrasiloxane and squalane. Lubricated contacts display a
      remarkable friction reduction, with liquid and substrate specific friction
      coefficients. Comparison with molecular dynamics simulations suggests that load
      bearing boundary layers at junction entrance cause the appearance of Amontons'
      law and impart atomic-scale character to the sliding process; continuum friction
      models are on the contrary of limited predictive power when applied to
      lubrication effects. An attempt is done to define general working conditions
      leading to the manifestation of nanoscale lubricity due to adsorbed boundary
      layers.

PMID- 16965107
TI  - Adsorption of model surfactantlike copolymers on nanopatterned surfaces.
AB  - The adsorption of polymers, copolymers, surfactants, and biopolymers is often
      used to engineer surfaces. Towards improving our understanding of polymer
      adsorption we report simulation results for the adsorption of model copolymers,
      resembling surfactants, on nanoscale patterned hydrophobic surfaces at infinitely
      dilute concentrations. The surfactants are composed by a hydrophobic tail and a
      hydrophilic head. Surfactant adsorption on the hydrophobic surface occurs in the
      tail-down configuration in which the tail segments are in contact with the
      surface. We investigate how the presence of a solid hard mask, used to create the
      nanoscale pattern on the underlying hydrophobic surface, affects the surfactant
      adsorption. We find that surfactant adsorption on the underlying hydrophobic
      surface is prevented when the characteristic dimensions of the solid hard mask
      are less than twice the radius of gyration. We also show that details about mask
      surfactant head effective interactions have the potential to alter the
      characteristics of adsorption. When the mask repels the head segments, the
      surfactants hardly adsorb on the underlying hydrophobic surface. When the mask
      strongly attracts the surfactant heads, the surfactants may preferentially adsorb
      on the mask rather than on the underlying hydrophobic surface. Under these latter
      circumstances the adsorbed surfactants in some cases assume a head-down
      configuration in which the head segments are in contact with the mask and the
      tail segments extend towards the bulk solution. We explain our results in terms
      of enthalpy and entropy of adsorption and discuss practical implications.

PMID- 16965108
TI  - The anisotropic hard-sphere crystal-melt interfacial free energy from
      fluctuations.
AB  - We have calculated the interfacial free energy for the hard-sphere system, as a
      function of crystal interface orientation, using a method that examines the
      fluctuations in the height of the interface during molecular dynamics
      simulations. The approach is particularly sensitive for the anisotropy of the
      interfacial free energy. We find an average interfacial free energy of
      gamma=0.56+/-0.02k(B)Tsigma(-2). This value is lower than earlier results based
      upon direct calculations of the free energy [R. L. Davidchack and B. B. Laird,
      Phys. Rev. Lett. 85, 4751 (2000)]. However, both the average value and the
      anisotropy agree with the recent values obtained by extrapolation from direct
      calculations for a series of the inverse-power potentials [R. L. Davidchack and
      B. B. Laird, Phys. Rev. Lett. 94, 086102 (2005)].

PMID- 16965109
TI  - Electronic transportation through asymmetrically substituted oligo(phenylene
      ethynylene)s: studied by first principles nonequilibrium Green's function
      formalism.
AB  - Theoretical investigations of a series of asymmetrically substituted conducting
      molecular wires [oligo(phenylene ethynylene)s] have been carried out using
      density functional theory and nonequilibrium Green's function formalism. To get
      the molecular rectification, the electron-donating group (-NH2) and the electron
      withdrawing group (-NO2) are placed on the different positions of the molecular
      wire. The dependences of spatial distribution and lowest unoccupied molecular
      orbital (LUMO) energy level on the applied voltage have been found playing
      dominating but opposite roles in controlling the rectification behavior. In the
      tested bias range, since the shift LUMO energy level is more important, the
      electrons transfer more easily from donor to acceptor through the molecular
      junction in general.

PMID- 16965110
TI  - Polarizable contributions to the surface tension of liquid water.
AB  - Surface tension, gamma, strongly affects interfacial properties in fluids. The
      degree to which polarizability affects gamma in water is thus far not well
      established. To address this situation, we carry out molecular dynamics
      simulations to study the interfacial forces acting on a slab of liquid water
      surrounded by vacuum using the Gaussian charge polarizable (GCP) model at 298.15
      K. The GCP model incorporates both a fixed dipole due to Gaussian distributed
      charges and a polarizable dipole. We find a well-defined bulklike region forms
      with a width of approximately 31 A. The average density of the bulklike region
      agrees with the experimental value of 0.997 g/cm3. However, we find that the
      orientation of the molecules in the bulklike region is strongly influenced by the
      interfaces, even at a distance five molecular diameters from the interface.
      Specifically, the orientations of both the permanent and induced dipoles show a
      preferred orientation parallel to the interface. Near the interface, the
      preferred orientation of the dipoles becomes more pronounced and the average
      magnitude of the induced dipoles decreases monotonically. To quantify the degree
      to which molecular orientation affects gamma, we calculate the contributions to
      gamma from permanent dipolar interactions, induced dipolar interactions, and
      dispersion forces. We find that the induced dipole interactions and the permanent
      dipole interactions, as well as the cross interactions, have positive
      contributions to gamma, and therefore contribute stability to the interface. The
      repulsive core interactions result in a negative contribution to gamma, which
      nearly cancels the positive contributions from the dipoles. The large negative
      core contributions to gamma are the result of small oxygen-oxygen separation
      between molecules. These small separations occur due to the strong attractions
      between hydrogen and oxygen atoms. The final predicted value for gamma (68.65
      m/Nm) shows a deviation of approximately 4% of the experimental value of 71.972
      m/Nm. The inclusion of polarization is critical for this model to produce an
      accurate value.

PMID- 16965111
TI  - The behavior of reorientational correlation functions of water at the water-lipid
      bilayer interface.
AB  - We studied the effects of confinement and the head group motion on the behavior
      of the reorientational correlation functions for water molecules at the
      water/lipid bilayer interface. The correlation functions were calculated from the
      data obtained from two molecular dynamics simulations: one with a flexible
      bilayer and the other with a frozen bilayer. In our present analysis the water
      molecules were separated into spatial regions according to their distance from
      the bilayer surface and into population groups, according to the length of their
      stay in the corresponding regions. We estimate that for most of the water
      molecules that are in a strongly confined environment of the transition region
      between the head groups and tails, and that solvate carbonyl groups, the decay
      time of their reorientational correlation functions is of the order of a few tens
      of picoseconds. Water molecules that stay inside the transition region for long
      periods of time can display longer time decay (of the order of hundreds of
      picoseconds). This latter long time decay is determined by the dynamics of the
      phospholipids, it is substantially reduced when the bilayer is frozen. The decay
      of the correlation functions for the interfacial water molecules that are
      solvating the head groups is also slowed down when compared to bulk, but just by
      factors of 3-4.

PMID- 16965112
TI  - Modeling electroosmotic and pressure-driven flows in porous microfluidic devices:
      zeta potential and porosity changes near the channel walls.
AB  - This work presents analytical solutions for both pressure-driven and
      electroosmotic flows in microchannels incorporating porous media. Solutions are
      based on a volume-averaged flow model using a scaling of the Navier-Stokes
      equations for fluid flow. The general model allows analysis of fluid flow in
      channels with porous regions bordering open regions and includes viscous forces,
      permitting consideration of porosity and zeta potential variations near channel
      walls. To obtain analytical solutions problems are constrained to the linearized
      Poisson-Boltzmann equation and a variation of Brinkman's equation [Appl. Sci.
      Res., Sect. A 1, 27 (1947); 1, 81 (1947)]. Cases include one continuous porous
      medium, two adjacent regions of different porosities, or one open channel
      adjacent to a porous region, and the porous material may have a different zeta
      potential than that of the channel walls. Solutions are described for two
      geometries, including flow between two parallel plates or in a cylinder. The
      model illustrates the relative importance of porosity and zeta potential in
      different regions of each channel.

PMID- 16965113
TI  - Kinetics and dynamic properties of equilibrium polymers.
AB  - The statistical mechanics and scission-recombination mechanism of self-assembling
      linear micelles are investigated by Brownian dynamics using a newly proposed
      mesoscopic model representing the micelles as equilibrium polymer chains. A
      semidilute concentration regime, yet dynamically unentangled, is considered over
      a wide range of scission/recombination rates. We focus on the analysis of short
      and long time behaviors of the scission and recombination mechanisms. Our results
      show that at time scales larger than the life time of the average chain length,
      the kinetics is in agreement with the mean-field kinetic model proposed by Cates
      and Candau [J. Phys.: Condens. Matter 2, 6869 (1990)] provided the kinetic
      constants are estimated as effective ones. These values do take into account
      through a transmission coefficient that a fraction of scission/recombination
      events is correlated over a short time (diffusion controlled mechanism) and thus
      turn out to be ineffective reactive events by annihilation effects. By studying
      macroscopic relaxation phenomena such as the average micelle length evolution
      after a T jump, the monomer diffusion, and the zero shear stress relaxation
      function, we confirm that the effective kinetic constants found are indeed the
      relevant parameters when macroscopic relaxation is coupled to the kinetics of
      micelles.

PMID- 16965114
TI  - The effect of copolymer composition on the dynamics of random copolymers in a
      homopolymer matrix.
AB  - The effect of copolymer composition on the dynamics of random copolymers in a
      homopolymer matrix is studied using computer simulations within the framework of
      the bond-fluctuation model on blends containing low concentrations (10%) of A-B
      copolymers, where A and B are two different types of monomers, dispersed in a
      homopolymer matrix of chains with only A-type monomers. Four copolymer
      compositions were studied, phi(A)=0.33, phi(A)=0.5, phi(A)=0.66, and phi(A)=0.82,
      while maintaining a statistically random sequence distribution. For this study,
      we have only included intermolecular interactions between A and B monomers. Our
      results indicate, in agreement with experimental data, that copolymer composition
      has an impact on system dynamics. Analysis of the structure reveals that
      copolymers with majority A content are expanded in the homopolymer matrix, have
      fewer interchain copolymer-copolymer contacts, and are well dispersed in the
      homopolymer matrix. On the other hand, copolymers with lower A content form a
      more compact structure, have more interchain contacts, and form aggregates that
      are short lived. This in turn leads to slower system dynamics. Both the radius of
      gyration (Rg) and copolymer end-to-end vectors (Re) increase with increasing A
      content until phi(A)=0.66 and then decrease. Copolymers with lower A content form
      more compact structures as the repulsive interactions between unlike species are
      minimized by the copolymers folding back on themselves and forming aggregates of
      copolymer chains. Thus, these results provide insight into the variation of
      copolymer dynamics with composition in the system by documenting the correlation
      between the thermodynamics of this mixture, the conformation of a copolymer chain
      in a homopolymer matrix, and the dynamics of both components in this blend.

PMID- 16965115
TI  - Virial coefficients and osmotic pressure in polymer solutions in good-solvent
      conditions.
AB  - We determine the second, third, and fourth virial coefficients appearing in the
      density expansion of the osmotic pressure Pi of a monodisperse polymer solution
      in good-solvent conditions. Using the expected large-concentration behavior, we
      extrapolate the low-density expansion outside the dilute regime, obtaining the
      osmotic pressure for any concentration in the semidilute region. Comparison with
      field-theoretical predictions and experimental data shows that the obtained
      expression is quite accurate. The error is approximately 1%-2% below the overlap
      concentration and rises at most to 5%-10% in the limit of very large polymer
      concentrations.

PMID- 16965116
TI  - Polymer size in dilute solutions in the good-solvent regime.
AB  - We determine the density expansion of the radius of gyration, of the hydrodynamic
      radius, and of the end-to-end distance for a monodisperse polymer solution in
      good-solvent conditions. We consider the scaling limit (large degree of
      polymerization), including the leading scaling corrections. Using the expected
      large-concentration behavior, we extrapolate these low-density expansions outside
      the dilute regime, obtaining a prediction for the radii for any concentration in
      the semidilute region. For the radius of gyration, comparison with field
      theoretical predictions shows that the relative error should be at most 5% in the
      limit of very large polymer concentrations.

PMID- 16965117
TI  - Insight into the role of hydration on protein dynamics.
AB  - The potential energy surface of a protein is rough. This intrinsic energetic
      roughness affects diffusion, and hence the kinetics. The dynamics of a system
      undergoing Brownian motion on this surface in an implicit continuum solvent
      simulation can be tuned via the frictional drag or collision frequency to be
      comparable to that of experiments or explicit solvent simulations. We show that
      the kinetic rate constant for a local rotational isomerization in stochastic
      simulations with continuum solvent and a collision frequency of 2 ps(-1) is about
      10(4) times faster than that in explicit water and experiments. A further
      increase in the collision frequency to 60 ps(-1) slows down the dynamics, but
      does not fully compensate for the lack of explicit water. We also show that the
      addition of explicit water does not only slow down the dynamics by increasing the
      frictional drag, but also increases the local energetic roughness of the energy
      landscape by as much as 1.0 kcal/mol.

PMID- 16965118
TI  - A new quantum method for electrostatic solvation energy of protein.
AB  - A new method that incorporates the conductorlike polarizable continuum model
      (CPCM) with the recently developed molecular fractionation with conjugate caps
      (MFCC) approach is developed for ab initio calculation of electrostatic solvation
      energy of protein. The application of the MFCC method makes it practical to apply
      CPCM to calculate electrostatic solvation energy of protein or other
      macromolecules in solution. In this MFCC-CPCM method, calculation of protein
      solvation is divided into calculations of individual solvation energies of
      fragments (residues) embedded in a common cavity defined with respect to the
      entire protein. Besides computational efficiency, the current approach also
      provides additional information about contribution to protein solvation from
      specific fragments. Numerical studies are carried out to calculate solvation
      energies for a variety of peptides including alpha helices and beta sheets.
      Excellent agreement between the MFCC-CPCM result and those from the standard full
      system CPCM calculation is obtained. Finally, the MFCC-CPCM calculation is
      applied to several real proteins and the results are compared to classical
      molecular mechanics Poisson-Boltzmann (MM/PB) and quantum Divid-and-Conque
      Poisson-Boltzmann (D&C-PB) calculations. Large wave function distortion energy
      (solute polarization energy) is obtained from the quantum calculation which is
      missing in the classical calculation. The present study demonstrates that the
      MFCC-CPCM method is readily applicable to studying solvation of proteins.

PMID- 16965119
TI  - Determination of conformational free energies of peptides by multidimensional
      adaptive umbrella sampling.
AB  - We improve the multidimensional adaptive umbrella sampling method for the
      computation of conformational free energies of biomolecules. The conformational
      transition between the alpha-helical and beta-hairpin conformational states of an
      alanine decapeptide is used as an example. Convergence properties of the weighted
      histogram-analysis-based adaptive umbrella sampling can be improved by using
      multiple replicas in each adaptive iteration and by using adaptive updating of
      the bounds of the umbrella potential. Using positional root-mean-square
      deviations from structures of the alpha-helical and beta-hairpin reference states
      as reaction coordinates, we obtained well-converged free energy surfaces of both
      the in-vacuum and in-solution decapeptide systems. From the free energy surfaces
      well-converged relative free energies between the two conformational states can
      be derived. Advantages and disadvantages of different methods for obtaining
      conformational free energies as well as implications of our results in studying
      conformational transitions of proteins and in improving force field are
      discussed.

PMID- 16965120
TI  - A theoretical study of conformational properties of dendritic block copolymers of
      first generation.
AB  - Conformational properties of a dendritic block copolymer of the first generation
      are studied by means of an analytic calculation and dimensionality techniques.
      The polymer can have different functionalities and branch lengths in the interior
      region and the exterior shell. Three parameters are included in order to describe
      the intensity of the interactions between the same or different monomeric units.
      Based on the average end to end distances of the branches effective angles are
      defined in order to study how the microscopic parameters control the position and
      activity of the end groups, but also the hollowness in the internal region and
      the tweezing ability of the external shell of the macromolecule.

PMID- 16965121
TI  - Lattice theory of ultrafast excitonic and charge-transfer dynamics in DNA.
AB  - We propose a lattice fermion model suitable for studying the ultrafast
      photoexcitation dynamics of ordered chains of deoxyribonucleic acid (DNA)
      polymers. The model includes both parallel (intrachain) and perpendicular (cross
      chain) terms as well as diagonal cross-chain terms coupling neighboring bases.
      The general form of our Hamiltonian is borrowed from lattice fermion models of
      quantum chromodynamics. The band structure for this model can be determined
      analytically, and we use this as a basis for computing the singly excited states
      of the poly(dA)poly(dT) DNA duplex using configuration interaction singles.
      Parameters for the model are taken from various literature sources and our own ab
      initio calculations. Results indicate that the excited states consist of a low
      energy band of dark charge-separated states followed by separate bands of
      delocalized excitonic states which have weak mixing between the thymidine and
      adenosine sides of the DNA chain. We then propose a lattice exciton model based
      upon the transition dipole-dipole couplings between bases and compare the
      analytical results for the survival probability of an initially localized exciton
      to exact numerical results. The results herein underscore the competing role of
      excitonic and charge-transfer dynamics in these systems.

PMID- 16965122
TI  - Role of monomer packing fraction in rubber elasticity.

PMID- 16965124
TI  - Collagen solubility correlates with skin optical clearing.
AB  - Biomedical optics and photomedicine applications are challenged by the turbidity
      of most biological tissue systems. Nonreactive, biocompatible chemical agents can
      induce a reversible reduction in optical scattering of collagenous tissues such
      as human skin. Herein we show that a chemical agent's tissue optical clearing
      potential is directly related to its collagen solubility, providing a rational
      design basis for effective, percutaneous formulations.

PMID- 16965125
TI  - Dual-color total internal reflection fluorescence cross-correlation spectroscopy.
AB  - We present the development and first application of a novel dual-color total
      internal reflection (TIR) fluorescence system for single-molecule coincidence
      analysis and fluorescence cross-correlation spectroscopy (FCCS). As a performance
      analysis, we measured a synthetic DNA-binding assay, demonstrating this dual
      color TIR-FCCS approach to be a suitable method for measuring coincidence assays
      such as biochemical binding, fusion, or signal transduction at solid/liquid
      interfaces. Due to the very high numerical aperture of the epi-illumination
      configuration, our setup provides a very high fluorescence collection efficiency
      resulting in a two- to three-fold increase in molecular brightness compared to
      conventional confocal FCCS. Further improvements have been achieved through
      global analysis of the spectroscopic data.

PMID- 16965126
TI  - Observation of dynamic subdomains in red blood cells.
AB  - We quantify the nanoscale structure and low-frequency dynamics associated with
      live red blood cells. The membrane displacements are measured using quantitative
      phase images provided by Fourier phase microscopy, with an average path-length
      stability of 0.75 nm over 45 min. The results reveal the existence of dynamic,
      independent subdomains across the cells that fluctuate at various dominant
      frequencies.

PMID- 16965127
TI  - Monitoring sarcomere structure changes in whole muscle using diffuse light
      reflectance.
AB  - Normal biomechanical and physiological functions of striated muscles are
      facilitated by the repeating sarcomere units. Light scattering technique has been
      used in studying single extracted muscle fibers. However, few studies, if any,
      have been conducted to investigate the possibility of using optical detection to
      examine sarcomere structure changes in whole muscles. We conducted a series of
      experiments to demonstrate that optical scattering properties measured in whole
      muscle are related to changes in sarcomere structure. These results suggest that
      photon migration technique has a potential for characterizing in vivo tissue
      ultrastructure changes in whole muscle.

PMID- 16965128
TI  - Respiration-induced changes in tissue blood volume distal to occluded artery,
      measured by photoplethysmography.
AB  - Photoplethysmography (PPG) measures the cardiac-induced fluctuations and other
      changes in tissue blood volume by light transmission measurement. In the current
      study, light transmission was simultaneously measured in the two index fingers of
      healthy subjects, while the brachial artery in the left arm was occluded by a
      pressure cuff, so that no PPG signal appeared in the left finger. Correlated
      respiratory-induced changes in the PPG baseline in the right hand and in the
      light transmission in the left hand were found, indicating respiratory-induced
      blood volume changes in the finger distal to the occluded artery. The blood
      volume changes under the PPG probe distal to the occluded artery are interpreted
      as transition of blood volume from small arteries into big veins, mediated by the
      sympathetic nervous system.

PMID- 16965129
TI  - Pioneers in biomedical optics: special section honoring professor Ashley J.
      Welch, University of Texas at Austin.

PMID- 16965130
TI  - Review of tissue simulating phantoms for optical spectroscopy, imaging and
      dosimetry.
AB  - Optical spectroscopy, imaging, and therapy tissue phantoms must have the
      scattering and absorption properties that are characteristic of human tissues,
      and over the past few decades, many useful models have been created. In this
      work, an overview of their composition and properties is outlined, by separating
      matrix, scattering, and absorbing materials, and discussing the benefits and
      weaknesses in each category. Matrix materials typically are water, gelatin, agar,
      polyester or epoxy and polyurethane resin, room-temperature vulcanizing (RTV)
      silicone, or polyvinyl alcohol gels. The water and hydrogel materials provide a
      soft medium that is biologically and biochemically compatible with addition of
      organic molecules, and are optimal for scientific laboratory studies. Polyester,
      polyurethane, and silicone phantoms are essentially permanent matrix compositions
      that are suitable for routine calibration and testing of established systems. The
      most common three choices for scatters have been: (1.) lipid based emulsions,
      (2.) titanium or aluminum oxide powders, and (3.) polymer microspheres. The
      choice of absorbers varies widely from hemoglobin and cells for biological
      simulation, to molecular dyes and ink as less biological but more stable
      absorbers. This review is an attempt to indicate which sets of phantoms are
      optimal for specific applications, and provide links to studies that characterize
      main phantom material properties and recipes.

PMID- 16965131
TI  - Preparation and characterization of polyurethane optical phantoms.
AB  - We describe a method for the preparation of a polyurethane phantom to simulate
      the optical properties of biologic tissues at two wavelengths in the visible and
      near-infrared spectral range. We characterize the addition of added molecular
      absorbers with relatively narrow absorption bands [full width at half maximum
      (FWHM) 32 and 76 nm for Epolight 6084 and 4148, respectively] for independent
      absorption at 690 nm for absorption up to 5 cm(-1), and 830 nm for absorptions up
      to 3 cm(-1). Absorption by both dyes is linear with concentration in these
      respective regions and is consistent in polyurethane both before and after
      curing. The dyes are stable over long durations with no more than 4% change. The
      absorption of visible light by polyurethane decreases with time and is stable by
      one year with a drop of 0.03+/-0.003 cm(-1) from 500 to 830 nm. The scattering
      properties are selected by the addition of TiO2 particles to the polyurethane,
      which we functionally describe for the 690- and 830-nm wavelengths as related to
      the weight per volume. We demonstrate that the variation in absorption and
      scattering properties for large batch fabrication (12 samples) is +/-3%. The
      optical properties of the phantoms have not significantly changed in a period of
      exceeding one year, which makes them suitable for use as a reference standard.

PMID- 16965132
TI  - Investigation of light propagation models to determine the optical properties of
      tissue from interstitial frequency domain fluence measurements.
AB  - Four models, standard diffusion approximation (SDA), single Monte Carlo (SMC),
      delta-P1, and isotropic similarity (ISM), are developed and evaluated as forward
      calculation tools in the estimation of tissue optical properties. The inverse
      calculation uses the ratio of the fluences and phase difference at two locations
      close to an intensity modulated isotropic source to recover the reduced
      scattering coefficient mus' and the absorption coefficient mua. Diffusion theory
      allows recovery of optical properties (OPs) within 5% for media with mus'mua>10.
      The performance of the delta-P1 model is similar to SDA, with limited enhanced
      accuracy. The collimation approximation may limit the use of the delta-P1 model
      for spherical geometry, and/or the fluence may not be accurately calculated by
      this model. The SMC model is the best, recovering OPs within 10% regardless of
      the albedo. However, the necessary restriction of the searched OPs space is
      inconvenient. The performance of ISM is similar to that of diffusion theory for
      media with mus'mua>10, and better for 1<mus'mua<10, i.e., determines absorption
      within 5% and reduced scattering within 20%. In practice, satisfactory estimates
      (within 5 to 10%) can be achieved using SDA to recover mus' and ISM to recover
      mua for media with mus'mua>5.

PMID- 16965133
TI  - Angular measurements of light scattered by turbid chiral media using linear
      Stokes polarimeter.
AB  - The effects of turbid chiral media on light polarization are studied in different
      directions around the scattering samples using a refined linear Stokes
      polarimeter, which simplifies the signal analysis, and allows for the detailed
      investigations of scattered light. Because no moving parts are involved in a
      measurement at a specific detection direction, the determination accuracy of
      polarization states is increased. The results show that light depolarization
      increases with both turbidity and detection angle for low and moderately turbid
      samples; however, the angular dependence decreases with increasing turbidity.
      When the turbidity is increased to approximately 100 cm(-1), the depolarization
      becomes higher in the forward than in the backward direction. Polarization
      sensitive Monte Carlo simulations are used to verify some experimental
      observations. The results also demonstrate that surviving linear polarization
      fraction and overall intensity are more sensitive to the increase of glucose
      concentration in backward than in the forward direction in highly turbid media,
      indicating that backward geometry may be preferable for potential glucose
      detection in a biomedical context. Comparison measurements with optically
      inactive glycerol suggest that the refractive index matching effect, and not the
      chiral nature of the solute, dominates the observed optical rotation engendered
      by glucose in highly turbid media.

PMID- 16965135
TI  - In vivo fluence rate measurements during Foscan-mediated photodynamic therapy of
      persistent and recurrent nasopharyngeal carcinomas using a dedicated light
      applicator.
AB  - The objective of this study was to evaluate the performance of a dedicated light
      applicator for light delivery and fluence rate monitoring during Foscan-mediated
      photodynamic therapy of nasopharyngeal carcinoma in a clinical phase I/II study.
      We have developed a flexible silicone applicator that can be inserted through the
      mouth and fixed in the nasopharyngeal cavity. Three isotropic fibers, for
      measuring of the fluence (rate) during therapy, were located within the
      nasopharyngeal tumor target area and one was manually positioned to monitor
      structures at risk in the shielded area. A flexible black silicon patch tailored
      to the patient's anatomy is attached to the applicator to shield the soft palate
      and oral cavity from the 652-nm laser light. Fourteen patients were included in
      the study, resulting in 26 fluence rate measurements in the risk volume (two
      failures). We observed a systematic reduction in fluence rate during therapy in
      20 out of 26 illuminations, which may be related to photodynamic therapy-induced
      increased blood content, decreased oxygenation, or reduced scattering. Our
      findings demonstrate that the applicator was easily inserted into the
      nasopharynx. The average light distribution in the target area was reasonably
      uniform over the length of the applicator, thus giving an acceptably homogeneous
      illumination throughout the cavity. Shielding of the risk area was adequate.
      Large interpatient variations in fluence rate stress the need for in vivo
      dosimetry. This enables corrections to be made for differences in optical
      properties and geometry resulting in comparable amounts of light available for
      Foscan absorption.

PMID- 16965134
TI  - Image reconstruction of effective Mie scattering parameters of breast tissue in
      vivo with near-infrared tomography.
AB  - A method for image reconstruction of the effective size and number density of
      scattering particles is discussed within the context of interpreting near
      infrared (NIR) tomography images of breast tissue. An approach to use Mie theory
      to estimate the effective scattering parameters is examined and applied, given
      some assumptions about the index of refraction change expected in lipid membrane
      bound scatterers. When using a limited number of NIR wavelengths in the reduced
      scattering spectra, the parameter extraction technique is limited to representing
      a continuous distribution of scatterer sizes, which is modeled as a simple
      exponentially decreasing distribution function. In this paper, image formation of
      effective scatterer size and number density is presented based on the estimation
      method. The method was evaluated with Intralipid phantom studies to demonstrate
      particle size estimation to within 9% of the expected value. Then the method was
      used in NIR patient images, and it indicates that for a cancer tumor, the
      effective scatterer size is smaller than the background breast values and the
      effective number density is higher. In contrast, for benign tumor patients, there
      is not a significant difference in effective scatterer size or number density
      between tumor and normal tissues. The method was used to interpret magnetic
      resonance imaging-coupled NIR images of adipose and fibroglandular tissues, and
      it indicated that the fibroglandular tissue has smaller effective scatterer size
      and larger effective number density than the adipose tissue does.

PMID- 16965136
TI  - Ratio of entropy to enthalpy in thermal transitions in biological tissues.
AB  - Thermal transitions in biological tissues that have been reported in the
      literature are summarized in terms of the apparent molar entropy (DeltaS) and
      molar enthalpy (DeltaH) involved in the transition. A plot of DeltaS versus
      DeltaH for all the data yields a straight line, consistent with the definition of
      free energy, DeltaG=DeltaH+TDeltaS. Various bonds may be involved in cooperative
      bond breakage during thermal transitions; however, for the sake of description,
      the equivalent number of cooperative hydrogen bonds can be cited. Most of the
      tissue data behave as if 10 to 20 hydrogen bonds are cooperatively broken during
      coagulation, with one transition, the expression of heat shock protein, involving
      90 cooperative hydrogen bonds. The data are consistent with DeltaS=a+bDeltaH,
      where a=-327.5 J(mol K) and b=31.47 x 10(-4) K(-1). If each additional hydrogen
      bond adds 19 x 10(3) Jmol to DeltaH, then each additional bond adds 59.8 J(mol K)
      to DeltaS. Hence, the dynamics of irreversible thermal transitions can be
      described in terms of one free parameter, the apparent number of cooperative
      hydrogen bonds broken during the transition.

PMID- 16965137
TI  - Porcine skin visible lesion thresholds for near-infrared lasers including
      modeling at two pulse durations and spot sizes.
AB  - With the advent of such systems as the airborne laser and advanced tactical
      laser, high-energy lasers that use 1315-nm wavelengths in the near-infrared band
      will soon present a new laser safety challenge to armed forces and civilian
      populations. Experiments in nonhuman primates using this wavelength have
      demonstrated a range of ocular injuries, including corneal, lenticular, and
      retinal lesions as a function of pulse duration. American National Standards
      Institute (ANSI) laser safety standards have traditionally been based on
      experimental data, and there is scant data for this wavelength. We are reporting
      minimum visible lesion (MVL) threshold measurements using a porcine skin model
      for two different pulse durations and spot sizes for this wavelength. We also
      compare our measurements to results from our model based on the heat transfer
      equation and rate process equation, together with actual temperature measurements
      on the skin surface using a high-speed infrared camera. Our MVL-ED50 thresholds
      for long pulses (350 micros) at 24-h postexposure are measured to be 99 and 83 J
      cm(-2) for spot sizes of 0.7 and 1.3 mm diam, respectively. Q-switched laser
      pulses of 50 ns have a lower threshold of 11 J cm(-2) for a 5-mm-diam top-hat
      laser pulse.

PMID- 16965138
TI  - Imaging techniques for research and education of thermal and mechanical
      interactions of lasers with biological and model tissues.
AB  - A setup based on color Schlieren techniques has been developed to study the
      interaction of energy sources, such as lasers, with biological tissues. This
      imaging technique enables real-time visualization of dynamic temperature
      gradients with high spatial and temporal resolution within a transparent tissue
      model. High-speed imaging techniques were combined in the setup to capture
      mechanical phenomena such as explosive vapor, cavitation bubbles, and shock
      waves. The imaging technique is especially used for qualitative studies because
      it is complex to obtain quantitative data by relating the colors in the images to
      temperatures. By positioning thermocouples in the field of view, temperature
      figures can be added in the image for correlation to colored areas induced by the
      temperature gradients. The color Schlieren setup was successfully used for
      various studies to obtain a better understanding of interaction of various laser,
      rf, and ultrasound devices used in medicine. The results contributed to the
      safety and the optimal settings of various medical treatments. Although the
      interaction of energy sources is simulated in model tissue, the video clips have
      proven to be of great value for educating researchers, surgeons, nurses, and
      students to obtain a better understanding of the mechanism of action during
      patient treatment.

PMID- 16965139
TI  - Noninvasive optoacoustic online retinal temperature determination during
      continuous-wave laser irradiation.
AB  - The therapeutic effect of most retinal laser treatments is initiated by a
      transient temperature increase. Although crucial to the effectiveness of the
      treatment, the temperature course is not exactly known due to individually
      different tissue properties. We develop an optoacoustic method to determine the
      retinal temperature increase in real time during continuous-wave (cw) laser
      irradiation, and perform temperature calculations to interpret the results
      exemplary for transpupillary thermotherapy (TTT). Porcine globes ex vivo and
      rabbit eyes in vivo are irradiated with a diode laser (lambda=810 nm, P< or =3 W,
      phi=2 mm) for 60 s. Simultaneously, pulses from a N2-laser pumped dye laser
      (lambda=500 nm, tau=3.5 ns, E approximately 5 microJ) are applied on the retina.
      Following its absorption, an ultrasonic pressure wave is emitted, which is
      detected by a transducer embedded in a contact lens. Using the previously
      measured temperature-dependent Gruneisen coefficient of chorioretinal tissue, a
      temperature raise in porcine eyes of 5.8 degrees C(Wcm2) after 60 s is observed
      and confirmed by simultaneous measurements with an inserted thermocouple. In a
      rabbit, we find 1.4 degrees C(Wcm2) with, and 2.2 degrees C(Wcm2) without
      perfusion at the same location. Coagulation of the rabbit's retina occurs at
      DeltaT=21 degrees C after 40 s. In conclusion, this optoacoustic method seems
      feasible for an in vivo real-time determination of temperature, opening the
      possibility for feedback control retinal laser treatments.

PMID- 16965140
TI  - Cell disintegration by laser-induced transient microbubbles and its simultaneous
      monitoring by interferometry.
AB  - Selective retina treatment (SRT) is a novel short pulsed laser therapy of several
      retinal diseases associated with a decreased metabolism at the retinal pigment
      epithelium (RPE). The range of laser pulse energies is small, in which the
      desired selective RPE disintegration is achieved without adverse effects to the
      neural retina. Thus, a real-time dosimetry control is required. We investigated a
      noninvasive interferometric technique able to monitor microbubble formation
      around the intracellular melanin granula, which is the origin of the desired RPE
      damage. A porcine ex vivo RPE model was irradiated by single pulses (350 ns1.7
      mus) of a neodymium: yttrium lithium fluoride laser (527 nm). The specimen was
      simultaneously probed by a Michelson interferometer (helium neon-laser: 633 nm)
      and by a hydrophone. Cell viability assays (Calcein-AM) were performed after
      irradiation. At threshold radiant exposure for cell death (ED(50)=129+/-5 mJ cm2
      for 350 ns; ED50=180+/-5 mJ cm2 for 1.7 mus), the interferometric transients
      changed due to microbubble formation. No major differences in the bubble dynamics
      were observed between both pulse durations. An algorithm to determine cell death
      from the interferometric transients showed less than 10% false positive or false
      negative results for the applied laser expositions compared to the viability
      assay. Interferometry is a reliable noncontact technique to monitor RPE
      disintegration and may serve as real-time dosimetry control during SRT.

PMID- 16965141
TI  - Optimizing heat shock protein expression induced by prostate cancer laser therapy
      through predictive computational models.
AB  - Thermal therapy efficacy can be diminished due to heat shock protein (HSP)
      induction in regions of a tumor where temperatures are insufficient to coagulate
      proteins. HSP expression enhances tumor cell viability and imparts resistance to
      chemotherapy and radiation treatments, which are generally employed in
      conjunction with hyperthermia. Therefore, an understanding of the thermally
      induced HSP expression within the targeted tumor must be incorporated into the
      treatment plan to optimize the thermal dose delivery and permit prediction of the
      overall tissue response. A treatment planning computational model capable of
      predicting the temperature, HSP27 and HSP70 expression, and damage fraction
      distributions associated with laser heating in healthy prostate tissue and tumors
      is presented. Measured thermally induced HSP27 and HSP70 expression kinetics and
      injury data for normal and cancerous prostate cells and prostate tumors are
      employed to create the first HSP expression predictive model and formulate an
      Arrhenius damage model. The correlation coefficients between measured and model
      predicted temperature, HSP27, and HSP70 were 0.98, 0.99, and 0.99, respectively,
      confirming the accuracy of the model. Utilization of the treatment planning model
      in the design of prostate cancer thermal therapies can enable optimization of the
      treatment outcome by controlling HSP expression and injury.

PMID- 16965142
TI  - Assessing laser-tissue damage with bioluminescent imaging.
AB  - Effective medical laser procedures are achieved by selecting laser parameters
      that minimize undesirable tissue damage. Traditionally, human subjects, animal
      models, and monolayer cell cultures have been used to study wound healing, tissue
      damage, and cellular effects of laser radiation. Each of these models has
      significant limitations, and consequently, a novel skin model is needed. To this
      end, a highly reproducible human skin model that enables noninvasive and
      longitudinal studies of gene expression was sought. In this study, we present an
      organotypic raft model (engineered skin) used in combination with bioluminescent
      imaging (BLI) techniques. The efficacy of the raft model was validated and
      characterized by investigating the role of heat shock protein 70 (hsp70) as a
      sensitive marker of thermal damage. The raft model consists of human cells
      incorporated into an extracellular matrix. The raft cultures were transfected
      with an adenovirus containing a murine hsp70 promoter driving transcription of
      luciferase. The model enables quantitative analysis of spatiotemporal expression
      of proteins using BLI. Thermal stress was induced on the raft cultures by means
      of a constant temperature water bath or with a carbon dioxide (CO2) laser
      (lambda=10.6 microm, 0.679 to 2.262 Wcm2, cw, unfocused Gaussian beam, omegaL=4.5
      mm, 1 min exposure). The bioluminescence was monitored noninvasively with an IVIS
      100 Bioluminescent Imaging System. BLI indicated that peak hsp70 expression
      occurs 4 to 12 h after exposure to thermal stress. A minimum irradiance of 0.679
      Wcm2 activated the hsp70 response, and a higher irradiance of 2.262 Wcm2 was
      associated with a severe reduction in hsp70 response due to tissue ablation.
      Reverse transcription polymerase chain reaction demonstrated that hsp70 mRNA
      levels increased with prolonged heating exposures. Enzyme-linked immunosorbent
      protein assays confirmed that luciferase was an accurate surrogate for hsp70
      intracellular protein levels. Hematoxylin and eosin stains verified the presence
      of the thermally denatured tissue regions. Immunohistochemical analyses confirmed
      that maximal hsp70 expression occurred at a depth of 150 microm. Bioluminescent
      microscopy was employed to corroborate these findings. These results indicate
      that quantitative BLI in engineered tissue equivalents provides a powerful model
      that enables sequential gene expression studies. Such a model can be used as a
      high throughput screening platform for laser-tissue interaction studies.

PMID- 16965143
TI  - Laser-induced transepidermal elimination of dermal content by fractional
      photothermolysis.
AB  - The wound healing process in skin is studied in human subjects treated with
      fractional photothermolysis. In-vivo histological evaluation of vacuoles formed
      over microthermal zones (MTZs) and their content is undertaken. A 30-W, 1550-nm
      single-mode fiber laser system delivers an array of 60 microm or 140 microm 1e2
      incidence microbeam spot size at variable pulse energy and density. Treatments
      span from 6 to 20 mJ with skin excisions performed 1-day post-treatment. Staining
      with hematoxylin and eosin demonstrates an intact stratum corneum with vacuolar
      formation within the epidermis. The re-epithelialization process with
      repopulation of melanocytes and keratinocytes at the basal layer is apparent by 1
      day post-treatment. The dermal-epidermal (DE) junction is weakened and separated
      just above zones of dermal coagulation. Complete loss of dermal cell viability is
      noted within the confines of the MTZs 1-day post-treatment, as assessed by
      lactate dehydrogenase. All cells falling outside the irradiation field remain
      viable. Content within the epidermal vacuoles stain positively with Gomori
      trichrome, suggesting a dermal origin. However, the positive staining could be
      due to loss of specificity after thermal alteration. Nevertheless, this dermal
      extrusion hypothesis is supported by very specific positive staining with an
      antihuman elastin antibody. Fractional photothermolysis creates microthermal
      lesions that allow transport and extrusion of dermal content through a
      compromised DE junction. Some dermal material is incorporated into the
      microepidermal necrotic debris and shuttled up the epidermis to eventually be
      exfoliated through the stratum corneum. This is the first report of a nonablative
      laser-induced transport mechanism by which dermal content can be predictably
      extruded biologically through the epidermis. Thus, treatment with the 1550-nm
      fiber laser may provide the first therapeutic option for clinical indications,
      including pigmentary disorders such as medically recalcitrant melasma, solar
      elastosis, as well as depositional diseases such as mucinosis and amyloidosis.

PMID- 16965144
TI  - Comparative study of cryogen spray cooling with R-134a and R-404a: implications
      for laser treatment of dark human skin.
AB  - Cutaneous laser treatment in dark skin patients is challenging due to significant
      light absorption by the melanin at the basal layer of epidermis, which can result
      in irreversible nonspecific thermal injury to the epidermis. Cryogen spray
      cooling (CSC) with R-134a (boiling point approximately -26.2 degrees C at 1 atm),
      which is currently used during cutaneous laser treatment, has shown poor efficacy
      in protecting dark human skin. We investigated the potential of CSC with R-404a
      (boiling point approximately -46.5 degrees C at 1 atm), which has a lower boiling
      point than R-134a, for improved therapeutic outcome in dark human skin at three
      levels: in vitro (epoxy resin skin phantom), ex vivo (normal dark human skin
      sample), and in vivo (skin of the rabbit external ear). The skin phantom was used
      to acquire the surface and internal temperature profiles in response to CSC with
      R-134a or R-404a at various spurt durations, based upon which CSC-induced heat
      removal from the skin phantom was estimated using an algorithm that solved a one
      dimensional inverse heat conduction problem. CSC with R-404a increased the
      temperature reductions within the phantom and subsequently the amount of heat
      removal from the phantom in comparison to that with R-134a. Normal ex vivo
      Fitzpatrick types V-VI human skin samples were used to investigate the thermal
      response of dark human skin epidermis to CSC (R-134a or R-404a) at various spurt
      durations in conjunction with 595-nm pulsed dye laser irradiation at various
      radiant exposures. Cryogen R-404a increased the threshold radiant exposures for
      irreversible thermal injury to the epidermis in dark pigmentation skin. No
      obvious CSC-induced morphological changes to human skin was observed when sprayed
      with R404-a spurts using durations up to 300 ms. In vivo rabbit ear vasculature
      was used as a model of cutaneous anomalies to assess the influences of CSC (with
      R-134a or R-404a) on the photothermolysis of dermal blood vessels. CSC (R-134a or
      R-404a) with the spurt durations of 100 to 300 ms increased the most superficial
      depth of thermally damaged dermal blood vessel compared with the sites without
      CSC, implying possible nonspecific cooling of superficial dermal blood vessels by
      the cryogen spurts with the settings applied.

PMID- 16965145
TI  - Dehydration mechanism of optical clearing in tissue.
AB  - Previous studies identified various mechanisms of light scattering reduction in
      tissue induced by chemical agents. Our results suggest that dehydration is an
      important mechanism of optical clearing in collagenous and cellular tissue.
      Photographic and optical coherence tomography images indicate that air-immersed
      skin and tendon specimens become similarly transparent to glycerol-immersed
      specimens. Transmission electron microscopy images reveal that dehydration causes
      individual scattering particles such as collagen fibrils and organelles to become
      more densely packed, but does not significantly alter size. A heuristic particle
      interaction model predicts that the scattering particle volume fraction increase
      can contribute substantially to optical clearing in collagenous and cellular
      tissue.

PMID- 16965146
TI  - Using sandpaper for noninvasive transepidermal optical skin clearing agent
      delivery.
AB  - We present a gentle mechanical method for the noninvasive transepidermal delivery
      of topically applied optical skin clearing agents. Optical skin clearing reduces
      light scattering in highly turbid skin with the aid of hyperosmotic chemicals
      such as glycerol, polyethylene glycol, and solutions of dextrose. Transepidermal
      delivery of such agents is believed to be most patient compliant and most likely
      to be used in a clinical environment. Optical skin clearing has the potential to
      expand the current limited use of laser light in medicine for diagnostic and
      therapeutic applications. Light scattering limits the penetration depth of
      collimated light into skin. In order to increase the diffusion of topically
      applied optical skin clearing agents into skin, we present a gentle mechanical
      delivery method involving glycerol and dextrose as optical skin clearing agents
      and fine 220-grit sandpaper to rub the clearing agent into the tissue. Gentle
      rubbing causes abrasion of the superficial skin layer including the stratum
      corneum, which otherwise prevents these optical skin clearing agents from freely
      diffusing into skin. Results indicate very fast optical skin clearing rates. In
      vivo hamster skin turned transparent within 2 min. The 1e light penetration depth
      increased by 36+/-3.75% for dextrose and 43+/-8.24% for glycerol. Optical skin
      clearing was reversed using phosphate buffered saline solution. Skin viability
      was observed 70 h post-treatment and showed scabbing and erythema on a few
      percent of the total optically cleared skin surface.

PMID- 16965147
TI  - Effect of optical tissue clearing on spatial resolution and sensitivity of
      bioluminescence imaging.
AB  - In vivo bioluminescence imaging (BLI) is a powerful method of in vivo molecular
      imaging based on the use of optically active luciferase reporter genes. Although
      this method provides superior sensitivity relative to other in vivo imaging
      methods, spatial resolution is poor due to light scattering. The objective of
      this study was to use hyperosmotic agents to reduce the scattering coefficient
      and hence improve spatial resolution of the BLI method. A diffusing fiber tip was
      used to simulate an isotropic point source of bioluminescence emission (550 to
      650 nm). Mouse skin was treated in vitro and in vivo with glycerol (50%, 30 min)
      and measurements of optical properties, and imaging photon counts were made
      before, during, and after application of glycerol to the skin sample. Glycerol
      application to mouse skin had little effect on the absorption coefficient but
      reduced the reduced scattering coefficient by more than one order of magnitude.
      This effect was reversible. Consequently, the spot size (i.e., spatial
      resolution) of the bioluminescence point source imaged through the skin decreased
      by a factor of 2 (550-nm light) to 3 (650-nm light) after 30 min. Simultaneously,
      an almost twofold decrease in the amount of light detected by the BLI system was
      observed, despite the fact that total transmission increased 1.7 times. We have
      shown here that multiply scattered light is responsible for both observations. We
      have shown that applying a hyperosmotic clearing agent to the skin of small
      rodents has the potential to improve spatial resolution of BLI owing to a
      reduction in the reduced scattering coefficient in the skin by one order of
      magnitude. However, reducing the scattering coefficient reduces the amount of
      light reaching the camera due to a reduction in the amount of multiply scattered
      light that reaches the camera aperture and thus reducing the sensitivity of the
      method.

PMID- 16965148
TI  - Temperature-dependent optical properties of individual vascular wall components
      measured by optical coherence tomography.
AB  - Optical properties of tissues and tissue components are important parameters in
      biomedical optics. We report measurements of tissue refractive index n and the
      attenuation coefficient mu(t) using optical coherence tomography (OCT) of
      individual vascular wall layers and plaque components. Moreover, since the
      temperature dependence of optical properties is widely known, we compare
      measurements at room and body temperatures. A decrease of n and mu(t) is observed
      in all samples, with the most profound effect on samples with high lipid content.
      The sample temperature is of influence on the quantitative measurements within
      OCT images. For extrapolation of ex-vivo experimental results, especially for
      structures with high lipid content, this effect should be taken into account.

PMID- 16965149
TI  - Quantitative evaluation of optical coherence tomography signal enhancement with
      gold nanoshells.
AB  - Nanoshell-enhanced optical coherence tomography (OCT) is a novel technique with
      the potential for molecular imaging and improved disease detection. However,
      optimization of this approach will require a quantitative understanding of the
      influence of nanoshell parameters on detected OCT signals. In this study, OCT was
      performed at 1310 nm in water and turbid tissue-simulating phantoms to which
      nanoshells were added. The effect of nanoshell concentration, core diameter, and
      shell thickness on signal enhancement was characterized. Experimental results
      indicated trends that were consistent with predicted optical properties-a
      monotonic increase in signal intensity and attenuation with increasing shell and
      core size. Threshold concentrations for a 2-dB OCT signal intensity gain were
      determined for several nanoshell geometries. For the most highly backscattering
      nanoshells tested-291-nm core diameter, 25-nm shell thickness-a concentration of
      10(9) nanoshells/mL was needed to produce this signal increase. Based on these
      results, we discuss various practical considerations for optimizing nanoshell
      enhanced OCT. Quantitative experimental data presented here will facilitate
      optimization of OCT-based diagnostics and may also be relevant to other
      reflectance-based approaches as well.

PMID- 16965150
TI  - Measurement of optical path length change following pulsed laser irradiation
      using differential phase optical coherence tomography.
AB  - Differential phase optical coherence tomography (DPOCT) is introduced to measure
      optical path length changes in response to pulsed laser irradiation (585 nm). An
      analytical equation that includes thermoelastic surface displacement and
      thermorefractive index change is derived to predict optical path length change in
      response to pulsed laser irradiation for both "confined surface" and "free
      surface" model systems. The derived equation is tested by comparing predicted
      values with data recorded from experiments using two model systems.
      Thermorefractive index change and the thermal expansion coefficient are deduced
      from differential phase change (dDeltaphi) and temperature increase (DeltaT0)
      measurements. The measured n(T0)beta(T0)+dndT[=1.7410(-4)+/-1.710(-6) (1K)] in
      the free surface experiment matches with the National Institute of Standards and
      Technology (NIST) data value [=1.7710(-4) (1K)]. Exclusion of lateral thermal
      expansion in the analytical model for the confined surface experiment causes
      difference between the measured dndT[=-2.310(-4)+/-7.310(-6)(1K)] and the NIST
      value [=-9.4510(-5) (1K)]. In spite of the difference in the confined surface
      experiment, results of our studies indicate DPOCT can detect dynamic optical path
      length change in response to pulsed laser irradiation with high sensitivity, and
      applications to tissue diagnostics may be possible.

PMID- 16965151
TI  - Dual modality imaging of a novel rat model of ovarian carcinogenesis.
AB  - Ovarian cancer is the fifth leading cause of cancer death in women, in part
      because of the limited knowledge about early stage disease. We develop a novel
      rat model of ovarian cancer and perform a pilot study to examine the harvested
      ovaries with complementary optical imaging modalities. Rats are exposed to
      repeated daily dosing (20 days) with 4-vinylcyclohexene diepoxide (VCD) to cause
      early ovarian failure (model for postmenopause), and ovaries are directly exposed
      to 7,12-dimethylbenz(a)anthracene (DMBA) to cause abnormal ovarian proliferation
      and neoplasia. Harvested ovaries are examined with optical coherence tomography
      (OCT) and light-induced fluorescence (LIF) at one, three, and five months post
      DMBA treatment. VCD causes complete ovarian follicle depletion within 8 months
      after onset of dosing. DMBA induces abnormal size, cysts, and neoplastic changes.
      OCT successfully visualizes normal and abnormal structures (e.g., cysts, bursa,
      follicular remnant degeneration) and the LIF spectra show statistically
      significant changes in the ratio of average emission intensity at 390:450 nm
      between VCD-treated ovaries and both normal cycling and neoplastic DMBA-treated
      ovaries. Overall, this pilot study demonstrates the feasibility of both the novel
      animal model for ovarian cancer and the ability of optical imaging techniques to
      visualize ovarian function and health.

PMID- 16965152
TI  - Quantification of the wound healing using polarization-sensitive optical
      coherence tomography.
AB  - We use polarization-sensitive optical coherence tomography (PS-OCT) to monitor
      the wound healing process in vitro and in vivo, which are affected by various
      drugs. Five rabbit subjects are used for in vitro studies and another five are
      used for in vivo studies. The in vitro studies are conducted to compare the PS
      OCT images with histopathology. For each subject, three biopsy lesions are
      created on each ear: one site is not treated (control); the second site is
      treated with sphingosylphosphorylcholine, which is expected to promote healing;
      and the last is administered with tetraacetylphytosphingosine, which negatively
      affects the healing process. Each site is examined with a PS-OCT system at 1, 4,
      7, 10, and 14- days after wound generation. The variations of phase retardation
      values caused by the collagen morphology changes on wound sites are quantified
      for all cases. Our results suggest that PS-OCT may be a useful tool for
      visualization of collagen fiber regeneration and for quantification of various
      drug effects during the wound healing process.

PMID- 16965153
TI  - Low-coherence enhanced backscattering: review of principles and applications for
      colon cancer screening.
AB  - The phenomenon of enhanced backscattering (EBS) of light, also known as coherent
      backscattering (CBS) of light, has been the object of intensive investigation in
      nonbiological media over the last two decades. However, there have been only a
      few attempts to explore EBS for tissue characterization and diagnosis. We have
      recently made progress in the EBS measurements in tissue by taking advantage of
      low spatial coherence illumination, which has led us to the development of low
      coherence enhanced backscattering (LEBS) spectroscopy. In this work, we review
      the current state of research on LEBS. After a brief discussion of the basic
      principle of EBS and LEBS, we present an overview of the unique features of LEBS
      for tissue characterization, and show that LEBS enables depth-selective
      spectroscopic assessment of mucosal tissue. Then, we demonstrate the potential of
      LEBS spectroscopy for predicting the risk of colon carcinogenesis and colonoscopy
      free screening for colorectal cancer (CRC).

PMID- 16965154
TI  - Line-scanning laser ophthalmoscope.
AB  - Scanning laser ophthalmoscopy (SLO) is a powerful imaging tool with specialized
      applications limited to research and ophthalmology clinics due in part to
      instrument size, cost, and complexity. Conversely, low-cost retinal imaging
      devices have limited capabilities in screening, detection, and diagnosis of
      diseases. To fill the niche between these two, a hand-held, nonmydriatic line
      scanning laser ophthalmoscope (LSLO) is designed, constructed, and tested on
      normal human subjects. The LSLO has only one moving part and uses a novel optical
      approach to produce wide-field confocal fundus images. Imaging modes include
      multiwavelength illumination and live stereoscopic imaging with a split aperture.
      Image processing and display functions are controlled with two stacked prototype
      compact printed circuit boards. With near shot-noise limited performance, the
      digital LSLO camera requires low illumination power (<500 microW) at near
      infrared wavelengths. The line-scanning principle of operation is examined in
      comparison to SLO and other imaging modes. The line-scanning approach produces
      high-contrast confocal images with nearly the same performance as a flying-spot
      SLO. The LSLO may significantly enhance SLO utility for routine use by
      ophthalmologists, optometrists, general practitioners, and also emergency medical
      personnel and technicians in the field for retinal disease detection and other
      diverse applications.

PMID- 16965155
TI  - Design and development of a computer-assisted retinal laser surgery system.
AB  - Since the mid-1980s, the development of a therapeutic, computer-assisted laser
      photocoagulation system to treat retinal disorders has progressed under the
      guidance of Dr. Welch, the Marion E. Forsman Centennial Professor of Engineering,
      Department of Biomedical Engineering, the University of Texas at Austin. This
      paper reviews the development of the system, related research in eye movement and
      laser-tissue interaction, and system implementation and testing. While subsets of
      these topics have been reported in prior publications, this paper brings the
      entire evolutionary design of the system together. We also discuss other recent
      "spinoff" uses of the system technology that have not been reported elsewhere and
      describe the impact of the latest technical advances on the overall system
      design.

PMID- 16965156
TI  - Prediction of glucose in whole blood by near-infrared spectroscopy: influence of
      wavelength region, preprocessing, and hemoglobin concentration.
AB  - Measurement accuracy for predicting glucose in whole blood was studied based on
      near-infrared spectroscopy. Optimal wavelength regions, preprocessing, and the
      influence of hemoglobin were examined using partial least-squares regression.
      Spectra between 1100 and 2400 nm were measured from 98 whole blood samples. In
      order to study the influence of hemoglobin, which is the most dominant component
      in blood, 98 samples were arranged such that glucose and hemoglobin
      concentrations were distributed in their physiological ranges. Samples were
      grouped into three depending on hemoglobin level. The results showed that glucose
      prediction was influenced by hemoglobin concentrations in the calibration model.
      It was necessary for samples used in the calibration model to represent the
      entire range of hemoglobin level. The cross-validation errors were the smallest
      when the wavelength regions of 1390 to 1888 nm and 2044 to 2393 nm were used.
      However, prediction accuracy was not very dependent on preprocessing methods in
      this optimal region. The standard error of glucose prediction was 25.5 mgdL and
      the coefficient of variation in prediction was 11.2%.

PMID- 16965157
TI  - Linear response range characterization and in vivo application of laser speckle
      imaging of blood flow dynamics.
AB  - Noninvasive blood flow imaging can provide critical information on the state of
      biological tissue and the efficacy of approaches to treat disease. With laser
      speckle imaging (LSI), relative changes in blood flow are typically reported,
      with the assumption that the measured values are on a linear scale. A linear
      relationship between the measured and actual flow rate values has been suggested.
      The actual flow rate range, over which this linear relationship is valid, is
      unknown. Herein we report the linear response range and velocity dynamic range
      (VDR) of our LSI instrument at two relevant camera integration times. For
      integration times of 1 and 10 ms, the best case VDR was 80 and 60 dB,
      respectively, and the worst case VDR was 20 and 50 dB. The best case VDR values
      were similar to those reported in the literature for optical Doppler tomography.
      We also demonstrate the potential of LSI for monitoring blood flow dynamics in
      the rodent dorsal skinfold chamber model. These findings imply that LSI can
      provide accurate wide-field maps of microvascular blood flow rate dynamics and
      highlight heterogeneities in flow response to the application of exogenous
      agents.

PMID- 16965158
TI  - Analysis of sperm motility using optical tweezers.
AB  - This study examines the use of optical trapping as a quantitative measure of
      sperm motility. The effects of laser trap duration and laser trapping power on
      sperm motility are described between sperm swimming force, swimmimg speed, and
      speed of progression (SOP) score. Sperm (SOP scores of 2-4) were trapped by a
      continuous-wave 1064 nm single-point gradient laser trap. Trap duration effects
      were quantified for 15, 10, and 5 seconds at 420 mW laser power. Laser power
      effects were quantified at powers of 420 mW, 350 mW, 300 mW, and 250 mW for five
      seconds. Swimming force, swimming speed, and SOP score relationships were
      examined at a trap duration and trapping power shown to minimally affect sperm
      motility. Swimming forces were measured by trapping sperm and subsequently
      decreasing laser power until the sperm escaped the trap. Swimming trajectories
      were calculated by custom-built software, and SOP scores were assigned by three
      qualified sperm scoring experts. A ubiquitous class of sperm were identified that
      swim with relatively high forces that are uncorrelated to swimming speed. It is
      concluded that sperm swimming forces measured by optical trapping provide new and
      valuable quantitative information to assess sperm motility.

PMID- 16965159
TI  - Ultrasharp light-scattering resonances of structured nanospheres: effects of size
      dependent dielectric functions.
AB  - Recently, Chen et al. [J. Biomed. Opt. Vol. 10, 024005 (2005)] reported on the
      concept of multicolor molecular imaging, which uses resonant light-scattering
      spectroscopy of multilayer nanospheres. They claimed that the resonance
      scattering peaks of three-layer nanoshells can be designed so that the ultrasharp
      widths are as narrow as 10 nm. Here we show that such ultrasharp labels cannot be
      fabricated in reality because the effects of size-dependent dielectric functions
      result in the five- to tenfold broadening of resonant scattering peaks.
      Furthermore, contrary to the data of Chen et al., we did not find any significant
      advantages of three-layer structures, as compared with the usual silica/metal
      nanoshells.

PMID- 16965160
TI  - In vivo assessment and evaluation of lung tissue morphologic and physiological
      changes from non-contact endoscopic reflectance spectroscopy for improving lung
      cancer detection.
AB  - We present a method for lung cancer detection exploiting reflectance spectra
      measured in vivo during endoscopic imaging of the lung. The measured reflectance
      spectra were analyzed using a specially developed light-transport model to obtain
      quantitative information about cancer-related, physiological, and morphologic
      changes in the superficial bronchial mucosa layers. The light-transport model
      allowed us to obtain the absorption coefficient (mua) and further to derive the
      micro-vascular blood volume fraction in tissue and the tissue blood oxygen
      saturation. The model also allowed us to obtain the scattering coefficient (mus)
      and the anisotropy coefficient (g) and further to derive the tissue scattering
      micro-particle volume fraction and size distribution. The specular component of
      the reflectance signal and the instrument response were accounted for during the
      analysis. The method was validated using 100 reflectance spectra measured in vivo
      in a noncontact fashion from 22 lung patients (50 normal tissue/benign lesion
      sites and 50 malignant lesion sites). The classification between normal
      tissue/benign lesions and malignant lesions was further investigated using the
      derived quantitative parameters and discriminant function analysis. The results
      demonstrated significant differences between the normal tissue/benign lesions and
      the malignant lesions in terms of tissue blood volume fraction, blood oxygen
      saturation, tissue scatterer volume fractions, and size distribution. The results
      also showed that the malignant lung lesions can be differentiated from normal
      tissue/benign lesions with both diagnostic sensitivity and specificity of better
      than 80%.

PMID- 16965161
TI  - Multiphoton excitation of fluorescent DNA base analogs.
AB  - Multiphoton excitation was used to investigate properties of the fluorescent DNA
      base analogs, 2-aminopurine (2AP) and 6-methylisoxanthopterin (6MI). 2
      aminopurine, a fluorescent analog of adenine, was excited by three-photon
      absorption. Fluorescence correlation measurements were attempted to evaluate the
      feasibility of using three-photon excitation of 2AP for DNA-protein interaction
      studies. However, high excitation power and long integration times needed to
      acquire high signal-to-noise fluorescence correlation curves render three-photon
      excitation FCS of 2AP not very useful for studying DNA base dynamics. The
      fluorescence properties of 6-methylisoxanthopterin, a guanine analog, were
      investigated using two-photon excitation. The two-photon absorption cross-section
      of 6MI was estimated to be about 2.5 x 10(-50) cm(4)s (2.5 GM units) at 700 nm.
      The two-photon excitation spectrum was measured in the spectral region from 700
      to 780 nm; in this region the shape of the two-photon excitation spectrum is very
      similar to the shape of single-photon excitation spectrum in the near-UV spectral
      region. Two-photon excitation of 6MI is suitable for fluorescence correlation
      measurements. Such measurements can be used to study DNA base dynamics and DNA
      protein interactions over a broad range of time scales.

PMID- 16965162
TI  - In vivo absorption, scattering, and physiologic properties of 58 malignant breast
      tumors determined by broadband diffuse optical spectroscopy.
AB  - Diffuse optical imaging (DOI) may be a beneficial diagnostic method for women
      with mammographically dense breast tissue. In order to evaluate the utility of
      DOI, we are developing broadband diffuse optical spectroscopy (DOS) to
      characterize the functional origins of optical signals in breast cancer patients.
      Broadband DOS combines multifrequency intensity-modulated and continuous-wave
      near-infrared light to quantify tissue absorption and scattering spectra from 650
      to 1000 nm. Values of intrinsic physiological properties (oxy- and deoxy
      hemoglobin, water, lipid, and scatter power) derived from absorption and
      scattering spectra provide detailed information on breast physiology. We present
      the results of clinical studies of 58 stage II/III malignant breast tumors using
      a noninvasive, handheld, broadband DOS probe. On average, eight positions were
      scanned over tumor and contralateral normal breast for each subject. Intrinsic
      physiological properties were statistically significantly different for malignant
      vs. normal tissues for all subjects, without patient age or tumor size/type
      stratification. Breast tissues containing malignant tumors displayed reduced
      lipid content ( approximately 20%) and increased water, deoxy-, and oxy
      hemoglobin (>50% each) compared to normal breast tissues. Functional
      perturbations by the tumor were significantly larger than functional variations
      in normal tissues. A tissue optical index (TOI) derived from intrinsic
      physiological properties yielded an average two-fold contrast difference between
      malignant tumors and intrinsic tissue properties. Our results demonstrate that
      intrinsic optical signals can be influenced by functional perturbations
      characteristic of malignant transformation; cellular metabolism, extracellular
      matrix composition, and angiogenesis. Our findings further underscore the
      importance of broadband measurements and patient age stratification in breast
      cancer DOI.

PMID- 16965163
TI  - Fourier-domain biophotoacoustic subsurface depth selective amplitude and phase
      imaging of turbid phantoms and biological tissue.
AB  - A novel photothermoacoustic imaging modality utilizing a frequency-swept
      (chirped) intensity-modulated laser source and coherent frequency domain signal
      processing ("biophotoacoustics") was introduced for noninvasive imaging of
      biological tissues. The developed frequency-domain imaging system takes advantage
      of linear frequency modulation waveforms to relate depth of tissue chromophores
      to the frequency spectrum of the detected acoustic response and of a narrow
      signal detection bandwidth to improve signal-to-noise ratio (SNR). Application of
      frequency-domain photothermoacoustic (FD-PTA) imaging was demonstrated using
      turbid phantoms and ex-vivo specimens of chicken breast with embedded absorbing
      inclusions simulating tumors.

PMID- 16965164
TI  - Fluorescence-enhanced optical tomography of a large tissue phantom using point
      illumination geometries.
AB  - We demonstrate fluorescence-enhanced optical imaging of single and multiple
      fluorescent targets within a large (approximately 1081 cm3) phantom using
      frequency-domain photon migration measurements of fluorescence collected at
      individual points in response to illumination of excitation light at individual
      points on the boundary. The tissue phantom was filled with a 1% lipid solution
      with and without 0.01 microM Indocyanine Green (ICG) and targets consisted of
      vials filled with the 1% lipid containing 1-2.5 microM ICG. Measurements were
      acquired using a modulated intensified CCD imaging system under different
      experimental conditions. For 3-D image reconstruction, the gradient-based penalty
      modified barrier function (PMBF) method with simple bounds constrained truncated
      Newton with trust region method (CONTN) was used. Targets of 0.5, 0.6, and 1.0
      cm3 at depths of 1.4-2.8 cm from the phantom surface were tomographically
      reconstructed. This work demonstrates the practicality of fluorescence-enhanced
      tomography in clinically relevant volumes.

PMID- 16965165
TI  - Time-gated optical system for depth-resolved functional brain imaging.
AB  - We present a time-domain optical system for functional imaging of the adult head.
      We first describe the instrument, which is based on a Ti:Sapphire pulsed laser
      (wavelength 750-850 nm) and an intensified CCD camera enabling parallel detection
      of multiple fibers. We characterize the system in terms of sensitivity and signal
      to-noise ratio, instrument response function, cross-talk, stability, and
      reproducibility. We then describe two applications of the instrument: the
      characterization of baseline optical properties of homogeneous scattering media,
      and functional brain imaging. For the second application, we developed a two-part
      probe consisting in two squares of 4 x 4 sources and 3 x 3 detectors. The laser
      source is time-multiplexed to define 4 states of 8 sources that can be turned on
      during the same camera frame while minimizing cross-talk. On the detection side,
      we use for each detector 7 fibers of different lengths creating an optical delay,
      and enabling simultaneous detection in 7 windows (by steps of 500 ps) for each
      detector. This multiple window detection allows depth sensitivity. The imaging
      probe was tested on dynamic phantoms and a preliminary result on an adult
      performing a motor task shows discrimination between superficial and cortical
      responses to the stimulus on both hemispheres.

PMID- 16965166
TI  - Analysis of near-infrared spectroscopy and indocyanine green dye dilution with
      Monte Carlo simulation of light propagation in the adult brain.
AB  - Near-infrared spectroscopy (NIRS) combined with indocyanine green (ICG) dilution
      is applied externally on the head to determine the cerebral hemodynamics of
      neurointensive care patients. We applied Monte Carlo simulation for the analysis
      of a number of problems associated with this method. First, the contamination of
      the optical density (OD) signal due to the extracerebral tissue was assessed.
      Second, the measured OD signal depends essentially on the relative blood content
      (with respect to its absorption) in the various transilluminated tissues. To take
      this into account, we weighted the calculated densities of the photon
      distribution under baseline conditions within the different tissues with the
      changes and aberration of the relative blood volumes that are typically observed
      under healthy and pathologic conditions. Third, in case of NIRS ICG dye dilution,
      an ICG bolus replaces part of the blood such that a transient change of
      absorption in the brain tissues occurs that can be recorded in the OD signal. Our
      results indicate that for an exchange fraction of Delta=30% of the relative blood
      volume within the intracerebral tissue, the OD signal is determined from 64 to
      74% by the gray matter and between 8 to 16% by the white matter maximally for a
      distance of d=4.5 cm.

PMID- 16965167
TI  - Computer-aided diagnosis of dysplasia in Barrett's esophagus using endoscopic
      optical coherence tomography.
AB  - Barrett's esophagus (BE) and associated adenocarcinoma have emerged as a major
      health care problem over the last two decades. Because of the widespread use of
      endoscopy, BE is being recognized increasingly in all Western countries. In
      clinical trials of endoscopic optical coherence tomography (EOCT), we defined
      certain image features that appear to be characteristic of precancerous
      (dysplastic) mucosa: decreased scattering and disorganization in the microscopic
      morphology. The objective of the present work is to develop computer-aided
      diagnosis (CAD) algorithms that aid the detection of dysplasia in BE. The image
      dataset used in the present study was derived from a total of 405 EOCT images (13
      patients) that were paired with highly correlated histologic sections of
      corresponding biopsies. Of these, 106 images were included in the study. The CAD
      algorithm used was based on a standard texture analysis method (center-symmetric
      auto-correlation). Using histology as the reference standard, this CAD algorithm
      had a sensitivity of 82%, specificity of 74%, and accuracy of 83%. CAD has the
      potential to quantify and standardize the diagnosis of dysplasia and allows high
      throughput image evaluation for EOCT screening applications. With further
      refinements, CAD could also improve the accuracy of EOCT identification of
      dysplasia in BE.

PMID- 16965168
TI  - Doppler optical coherence tomography to monitor the effect of photodynamic
      therapy on tissue morphology and perfusion.
AB  - We investigated the feasibility of using optical coherence tomography (OCT) for
      noninvasive real-time visualization of the vascular effects of photodynamic
      therapy (PDT) in normal and tumor tissue in mice. Perfusion control measurements
      were initially performed after administrating vaso-active drugs or clamping of
      the subcutaneous tumors. Subsequent measurements were made on tumor-bearing mice
      before and after PDT using the photosensitizer meta-tetrahydroxyphenylchlorin
      (mTHPC). Tumors were illuminated using either a short drug light interval (D-L, 3
      h), when mTHPC is primarily located in the tumor vasculature or a long D-L
      interval (48 h), when the drug is distributed throughout the whole tumor. OCT
      enabled visualization of the different layers of tumor, and overlying skin with a
      maximal penetration of < or =0.5-1 mm. PDT with a short D-L interval resulted in
      a significant decrease of perfusion in the tumor periphery, to 20% of pre
      treatment values at 160 min, whereas perfusion in the skin initially increased by
      10% (at 25 min) and subsequently decreased to 60% of pre-treatment values (at 200
      min). PDT with a long D-L interval did not induce significant changes in
      perfusion. The concept of using noninvasive OCT measurements for monitoring
      early, treatment-related changes in morphology and perfusion may have
      applications in evaluating effects of anti-angiogenic or antivascular (cancer)
      therapy.

PMID- 16965169
TI  - In vivo confocal scanning laser microscopy: comparison of the reflectance and
      fluorescence mode by imaging human skin.
AB  - Optical, noninvasive methods have become efficient in vivo tools in
      dermatological diagnosis and research. From these promising imaging techniques,
      only the confocal scanning laser microscopy (CSLM) provides visualization of
      subsurface skin structures with resolutions similar to those of light microscopy.
      Skin annexes, as well as cutaneous cells from different epidermal layers, can be
      distinguished excellently. Currently, two forms of application have been
      established in dermatological practice: the reflectance mode, predominantly in
      the clinical field, and the fluorescence mode in dermatological research.
      Differences in both methods exist in the preparative protocol, in maximum imaging
      depth and, particularly, in the gain of contrast extraction. The reflectance mode
      demonstrates naturally occurring tissue components, whereas the fluorescent CSLM
      achieves contrast by administering fluorescence dye, representing the dynamic
      distribution pattern of the dye's fluorescent emission. Therefore, the
      reflectance and fluorescent modes highlight various skin microstructures,
      providing dissimilar in vivo confocal images of the skin. This permits different
      predications and information on the state of the tissue. We report the advantages
      and disadvantages of both optical imaging modes. The comparison was drawn by
      scanning human skin in vivo. Representative images in varying depths were
      obtained and analyzed; preparation procedures are shown and discussed.

PMID- 16965170
TI  - Anomalous photobleaching in fluorescence recovery after photobleaching
      measurements due to excitation saturation--a case study for fluorescein.
AB  - In this study we examine the implications of excitation saturation on
      fluorescence recovery after photobleaching (FRAP) experiments. In particular we
      present both experimental and theoretical evidence that fluorescein, one of the
      most frequently used fluorophores in FRAP, does not always comply with the basic
      assumptions that are made in many FRAP models: an invariant bleaching
      illumination intensity distribution (BID) in combination with first-order
      photobleaching kinetics. High light intensity levels, which are typical for the
      photobleaching phase of FRAP experiments, can cause excitation saturation of
      fluorescein in the excited triplet state. We show by experiments and computer
      simulations that under such saturating conditions the higher-order diffraction
      maxima of the BID substantially contribute to the photobleaching process and can
      no longer be neglected. As a result, the bleached regions are larger than
      expected theoretically from the FRAP models. Although this effect is not always
      directly evident from the FRAP experiments, neglecting it may shift the
      calculated diffusion coefficient by as much as over one order of magnitude. We
      present a discussion on the implications of this saturation effect on various
      types of FRAP models.

PMID- 16965171
TI  - Fast optical signals in the peripheral nervous system.
AB  - We present a study of the near-infrared optical response to electrical
      stimulation of peripheral nerves. The sural nerve of six healthy subjects between
      the ages of 22 and 41 was stimulated with transcutaneous electrical pulses in a
      region located approximately 10 cm above the ankle. A two-wavelength (690 and 830
      nm) tissue spectrometer was used to probe the same sural nerve below the ankle.
      We measured optical changes that peaked 60 to 160 ms after the electrical
      stimulus. On the basis of the strong wavelength dependence of these fast optical
      signals, we argue that their origin is mostly from absorption rather than
      scattering. From these absorption changes, we obtain oxy- and deoxy-hemoglobin
      concentration changes that describe a rapid hemodynamic response to electrical
      nerve activation. In five out of six subjects, this hemodynamic response is an
      increase in total (oxy+deoxy) hemoglobin concentration, consistent with a fast
      vasodilation. Our findings support the hypothesis that the peripheral nervous
      system undergoes neurovascular coupling, even though more data is needed to prove
      such hypothesis.

PMID- 16965174
TI  - Scientific software development is not an oxymoron.

PMID- 16965175
TI  - Oscillatory regulation of Hes1: Discrete stochastic delay modelling and
      simulation.
AB  - Discrete stochastic simulations are a powerful tool for understanding the
      dynamics of chemical kinetics when there are small-to-moderate numbers of certain
      molecular species. In this paper we introduce delays into the stochastic
      simulation algorithm, thus mimicking delays associated with transcription and
      translation. We then show that this process may well explain more faithfully than
      continuous deterministic models the observed sustained oscillations in expression
      levels of hes1 mRNA and Hes1 protein.

PMID- 16965176
TI  - Imitating manual curation of text-mined facts in biomedicine.
AB  - Text-mining algorithms make mistakes in extracting facts from natural-language
      texts. In biomedical applications, which rely on use of text-mined data, it is
      critical to assess the quality (the probability that the message is correctly
      extracted) of individual facts--to resolve data conflicts and inconsistencies.
      Using a large set of almost 100,000 manually produced evaluations (most facts
      were independently reviewed more than once, producing independent evaluations),
      we implemented and tested a collection of algorithms that mimic human evaluation
      of facts provided by an automated information-extraction system. The performance
      of our best automated classifiers closely approached that of our human evaluators
      (ROC score close to 0.95). Our hypothesis is that, were we to use a larger number
      of human experts to evaluate any given sentence, we could implement an artificial
      intelligence curator that would perform the classification job at least as
      accurately as an average individual human evaluator. We illustrated our analysis
      by visualizing the predicted accuracy of the text-mined relations involving the
      term cocaine.

PMID- 16965177
TI  - Transient calcium and dopamine increase PKA activity and DARPP-32
      phosphorylation.
AB  - Reinforcement learning theorizes that strengthening of synaptic connections in
      medium spiny neurons of the striatum occurs when glutamatergic input (from
      cortex) and dopaminergic input (from substantia nigra) are received
      simultaneously. Subsequent to learning, medium spiny neurons with strengthened
      synapses are more likely to fire in response to cortical input alone. This
      synaptic plasticity is produced by phosphorylation of AMPA receptors, caused by
      phosphorylation of various signalling molecules. A key signalling molecule is the
      phosphoprotein DARPP-32, highly expressed in striatal medium spiny neurons. DARPP
      32 is regulated by several neurotransmitters through a complex network of
      intracellular signalling pathways involving cAMP (increased through dopamine
      stimulation) and calcium (increased through glutamate stimulation). Since DARPP
      32 controls several kinases and phosphatases involved in striatal synaptic
      plasticity, understanding the interactions between cAMP and calcium, in
      particular the effect of transient stimuli on DARPP-32 phosphorylation, has major
      implications for understanding reinforcement learning. We developed a computer
      model of the biochemical reaction pathways involved in the phosphorylation of
      DARPP-32 on Thr34 and Thr75. Ordinary differential equations describing the
      biochemical reactions were implemented in a single compartment model using the
      software XPPAUT. Reaction rate constants were obtained from the biochemical
      literature. The first set of simulations using sustained elevations of dopamine
      and calcium produced phosphorylation levels of DARPP-32 similar to that measured
      experimentally, thereby validating the model. The second set of simulations,
      using the validated model, showed that transient dopamine elevations increased
      the phosphorylation of Thr34 as expected, but transient calcium elevations also
      increased the phosphorylation of Thr34, contrary to what is believed. When
      transient calcium and dopamine stimuli were paired, PKA activation and Thr34
      phosphorylation increased compared with dopamine alone. This result, which is
      robust to variation in model parameters, supports reinforcement learning theories
      in which activity-dependent long-term synaptic plasticity requires paired
      glutamate and dopamine inputs.

PMID- 16965178
TI  - Designing siRNA that distinguish between genes that differ by a single
      nucleotide.
AB  - Small interfering RNAs (siRNAs), the guides that direct RNA interference (RNAi),
      provide a powerful tool to reduce the expression of a single gene in human cells.
      Ideally, dominant, gain-of-function human diseases could be treated using siRNAs
      that specifically silence the mutant disease allele, while leaving expression of
      the wild-type allele unperturbed. Previous reports suggest that siRNAs can be
      designed with single nucleotide specificity, but no rational basis for the design
      of siRNAs with single nucleotide discrimination has been proposed. We
      systematically identified siRNAs that discriminate between the wild-type and
      mutant alleles of two disease genes: the human Cu, Zn superoxide dismutase (SOD1)
      gene, which contributes to the progression of hereditary amyotrophic lateral
      sclerosis through the gain of a toxic property, and the huntingtin (HTT) gene,
      which causes Huntington disease when its CAG-repeat region expands beyond
      approximately 35 repeats. Using cell-free RNAi reactions in Drosophila embryo
      lysate and reporter assays and microarray analysis of off-target effects in
      cultured human cells, we identified positions within an siRNA that are most
      sensitive to mismatches. We also show that purine:purine mismatches imbue an
      siRNA with greater discriminatory power than other types of base mismatches.
      siRNAs in which either a G:U wobble or a mismatch is located in the "seed"
      sequence, the specialized siRNA guide region responsible for target binding,
      displayed lower levels of selectivity than those in which the mismatch was
      located 3' to the seed; this region of an siRNA is critical for target cleavage
      but not siRNA binding. Our data suggest that siRNAs can be designed to
      discriminate between the wild-type and mutant alleles of many genes that differ
      by just a single nucleotide.

PMID- 16965179
TI  - Genome-wide hierarchy of replication origin usage in Saccharomyces cerevisiae.
AB  - Replication origins in a genome are inherently different in their base sequence
      and in their response to temporal and cell cycle regulation signals for DNA
      replication. To investigate the chromosomal determinants that influence the
      efficiency of initiation of DNA replication genome-wide, we made use of a reverse
      strategy originally used for the isolation of replication initiation mutants in
      Saccharomyces cerevisiae. In yeast, replication origins isolated from chromosomes
      support the autonomous replication of plasmids. These replication origins,
      whether in the context of a chromosome or a plasmid, will initiate efficiently in
      wild-type cells but show a dramatically contrasted efficiency of activation in
      mutants defective in the early steps of replication initiation. Serial passages
      of a genomic library of autonomously replicating sequences (ARSs) in such a
      mutant allowed us to select for constitutively active ARSs. We found a hierarchy
      of preferential initiation of ARSs that correlates with local transcription
      patterns. This preferential usage is enhanced in mutants defective in the
      assembly of the prereplication complex (pre-RC) but not in mutants defective in
      the activation of the pre-RC. Our findings are consistent with an interference of
      local transcription with the assembly of the pre-RC at a majority of replication
      origins.

PMID- 16965180
TI  - Allele frequency matching between SNPs reveals an excess of linkage
      disequilibrium in genic regions of the human genome.
AB  - Significant interest has emerged in mapping genetic susceptibility for complex
      traits through whole-genome association studies. These studies rely on the extent
      of association, i.e., linkage disequilibrium (LD), between single nucleotide
      polymorphisms (SNPs) across the human genome. LD describes the nonrandom
      association between SNP pairs and can be used as a metric when designing
      maximally informative panels of SNPs for association studies in human
      populations. Using data from the 1.58 million SNPs genotyped by Perlegen, we
      explored the allele frequency dependence of the LD statistic r(2) both
      empirically and theoretically. We show that average r(2) values between SNPs
      unmatched for allele frequency are always limited to much less than 1
      (theoretical approximately 0.46 to 0.57 for this dataset). Frequency matching of
      SNP pairs provides a more sensitive measure for assessing the average decay of LD
      and generates average r(2) values across nearly the entire informative range
      (from 0 to 0.89 through 0.95). Additionally, we analyzed the extent of perfect LD
      (r(2) = 1.0) using frequency-matched SNPs and found significant differences in
      the extent of LD in genic regions versus intergenic regions. The SNP pairs
      exhibiting perfect LD showed a significant bias for derived, nonancestral
      alleles, providing evidence for positive natural selection in the human genome.

PMID- 16965181
TI  - Photosensitized DNA damage and its protection via a novel mechanism.
AB  - UVA, which accounts for approximately 95% of solar UV radiation, can cause
      mutations and skin cancer. Based mainly on the results of our study, this paper
      summarizes the mechanisms of UVA-induced DNA damage in the presence of various
      photosensitizers, and also proposes a new mechanism for its chemoprevention. UVA
      radiation induces DNA damage at the 5'-G of 5'-GG-3' sequence in double-stranded
      DNA through Type I mechanism, which involves electron transfer from guanine to
      activated photosensitizers. Endogenous sensitizers such as riboflavin and pterin
      derivatives and an exogenous sensitizer nalidixic acid mediate DNA photodamage
      via this mechanism. The major Type II mechanism involves the generation of
      singlet oxygen from photoactivated sensitizers, including hematoporphyrin and a
      fluoroquinolone antibacterial lomefloxacin, resulting in damage to guanines
      without preference for consecutive guanines. UVA also produces superoxide anion
      radical by an electron transfer from photoexcited sensitizers to oxygen (minor
      Type II mechanism), and DNA damage is induced by reactive species generated
      through the interaction of hydrogen peroxide with metal ions. The involvement of
      these mechanisms in UVA carcinogenesis is discussed. In addition, we found that
      xanthone derivatives inhibited DNA damage caused by photoexcited riboflavin via
      the quenching of its excited triplet state. It is thus considered that naturally
      occurring quenchers including xanthone derivatives may act as novel
      chemopreventive agents against photocarcinogenesis.

PMID- 16965182
TI  - Cognitive impairment and functional outcome in schizophrenia and bipolar
      disorder.
AB  - A considerable amount of evidence supports the relationship between cognitive
      impairment and functional outcomes in schizophrenia. Cognitive impairment is
      considered a core feature of schizophrenia that includes problems in speed of
      processing, attention/vigilance, working memory, verbal learning, visual
      learning, reasoning and problem solving, and social cognition. These deficits can
      also serve as an endophenotype for the illness in studies of genetics. Cognition
      is considered a reasonable treatment target in individuals with schizophrenia,
      partly because cognitive deficits contribute to poor functional outcomes.
      Similarly, evidence is beginning to emerge that cognitive impairment may also be
      a core feature of bipolar disorder. In addition, cognitive deficits adversely
      affect functional outcomes in bipolar disorder. This evidence suggests that
      cognition can be considered a reasonable target for intervention in both
      schizophrenia and bipolar disorder.

PMID- 16965183
TI  - The neurobiology of cognition in schizophrenia.
AB  - Currently, no drugs exist that effectively treat cognition in people with
      schizophrenia. What is known about the neurobiology of cognition in schizophrenia
      is derived from the animal literature; it is inadequate and superficial. Despite
      this lack, pharmacologic research into potential molecular targets has uncovered
      several viable possibilities from animal studies. A subcommittee of the
      Measurement and Treatment Research to Improve Cognition in Schizophrenia
      (MATRICS) program investigated the range of putative molecular targets for
      treating cognition. Those targets that show promise for pharmacologic focus
      include the dopamine receptors (especially D1) in the prefrontal cortex (PFC),
      the serotonin receptors in the PFC and anterior cingulate cortex, the
      glutamatergic excitatory synapse, the acetylcholine nicotinic receptors in the
      hippocampus, the acetylcholine muscarinic receptors, and the brain gamma
      aminobutyric acid (GABA) system. Once developed and tested, the effective
      compounds will be valuable for the treatment of the symptom domains of cognitive
      dysfunction and negative symptoms.

PMID- 16965184
TI  - Defining and achieving recovery from bipolar disorder.
AB  - Management of bipolar disorder in many ways is similar to the management of
      schizophrenia in that the goals in the treatment of both disorders are to avoid
      rehospitalization, manage behavioral symptoms, and promote functional recovery.
      This review will define functional recovery in bipolar disorder, discuss relapse
      prevention, and consider some implications for treatment. The most notable
      implication for treatment is that clinicians need to use stricter criteria when
      defining recovery in bipolar disorder. Recovery should not be defined merely by
      symptomatic remission or even syndromal remission; rather, recovery should
      include symptomatic recovery, syndromal recovery, functional recovery, and a
      return to an acceptable quality of life for the patient.

PMID- 16965185
TI  - Long-term management strategies to achieve optimal function in patients with
      bipolar disorder.
AB  - Functional impairment is a problem for people with bipolar disorder. Predictors
      of poor functional outcome are psychiatric and medical comorbidity, interepisode
      subsyndromal symptoms, psychosis during a manic or mixed episode, and low
      premorbid functioning. Cognitive dysfunction may also be a contributory factor in
      functional impairment. Several psychosocial interventions designed for people
      with bipolar disorder have demonstrated success in improving syndromal outcomes,
      but the effects of psychosocial interventions on functioning and cognition have
      not been examined. Among pharmacologic interventions available for long-term
      treatment of bipolar disorder, there is a strong clinical trend away from
      monotherapy and toward combination therapy. Lithium, lamotrigine, olanzapine, and
      aripiprazole have all shown substantial improvements in relapse rates compared
      with placebo. Although some of these medications show superior results compared
      with the others in preventing the recurrence of either depressive or manic
      episodes, only anecdotal evidence exists regarding their effect on cognition.
      Combination therapy with antipsychotics or antidepressants has also been shown to
      produce better syndromal outcomes in people with bipolar disorder, but inadequate
      evidence is available on cognitive outcomes. Substantial information is needed
      regarding the prevalence and causes of cognitive dysfunction in bipolar disorder,
      the effects of existing treatments on cognition, and long-term treatments to
      improve cognition and functioning.

PMID- 16965186
TI  - Medical risk in patients with bipolar disorder and schizophrenia.
AB  - Patients with schizophrenia and bipolar disorder are vulnerable to developing key
      modifiable risk factors for cardiovascular disease, such as obesity, smoking,
      hypertension, dyslipidemia, and type 2 diabetes mellitus. In addition, mood
      stabilizers, anticonvulsants, and antipsychotic medications, which are commonly
      used to treat schizophrenia and bipolar disorder, have been linked to risk for
      adverse metabolic changes in patients. This article reviews the current
      literature on the prevalence of medical risk factors in the general population as
      well as in those patients with schizophrenia or bipolar disorder and discusses
      treatment strategies and lifestyle changes that patients can make in order to
      reduce their risks for certain diseases.

PMID- 16965187
TI  - Drug initiatives to improve cognitive function.
AB  - Unlike for other chronic illnesses, the development of new medications for the
      treatment of schizophrenia has been relatively dormant since the 1950s. Recently,
      the Measurement and Treatment Research to Improve Cognition in Schizophrenia
      (MATRICS) program was established by the National Institute of Mental Health
      (NIMH) in order to facilitate the development of treatments for cognitive
      impairment and functional outcome in schizophrenia. Although effective
      medications for managing the positive symptoms of schizophrenia have permitted
      many patients to live in the community, these medications often fail to improve
      social and vocational function. As a result, some experts believe that research
      into new treatments should focus instead on the functional outcomes of patients
      by improving cognitive abilities and social competence. The MATRICS program
      brought together scientists from academia, government, and industry to discuss
      ways of promoting the development of new treatments for schizophrenia and gain
      consensus on treatment targets. The initiatives that have come out of the MATRICS
      program include focusing on adjunct medications, addressing regulatory issues
      with the U.S. Food and Drug Administration, determining the best way to measure
      functional outcomes, classifying symptoms, developing a battery of cognitive
      tests for assessing outcomes in clinical trials, and ranking promising targets
      for new treatment development.

PMID- 16965189
TI  - Introduction: the clinical impact of agitation in various psychiatric disorders:
      management consensus and controversies.

PMID- 16965190
TI  - A review of agitation in mental illness: burden of illness and underlying
      pathology.
AB  - Agitation has been poorly addressed as a unique entity in many psychiatric
      disorders. Recent medical literature and a range of instruments have measured
      agitation in various clinical settings. Agitation is a common problem in many
      patients with schizophrenia, bipolar mania, or dementia. Moreover, agitation
      adversely impacts many facets of the healing process, including direct patient
      care, caregiver burden, and community resources. Frontal lobe dysfunction and
      mutations in the catechol O-methyltransferase (COMT) gene involved in dopamine
      metabolism and catecholamine inactivation have been linked to agitation in
      patients with schizophrenia and bipolar disorder. Cerebral impairment and
      deficits in cognitive function predispose patients with dementia to agitation. In
      patients with Alzheimer's dementia, both frontal and temporal lobe pathology may
      be associated with agitation. Addressing agitation as a symptom of psychiatric
      illness would represent a great opportunity for therapeutic intervention and the
      alleviation of patient suffering, family burden, and societal costs.

PMID- 16965191
TI  - A review of agitation in mental illness: treatment guidelines and current
      therapies.
AB  - BACKGROUND: Agitation is an important therapeutic target in the acute and/or
      emergent setting, as well as for longer-term care of patients with psychiatric
      illness. METHOD: Select reviews and guidelines published (from 2000 to 2006) on
      the treatment of agitation in various psychiatric disorders were evaluated.
      RESULTS: After maximizing the safety of all individuals in the presence of an
      acutely agitated patient, initial therapy generally involves verbal deescalation.
      Pharmacologic management of acute agitation relies on typical antipsychotics,
      particularly haloperidol; benzodiazepines; and atypical antipsychotics. The
      selection of a specific agent (or combination of agents) should be guided by
      etiologic considerations, efficacy of the drug(s), side effects, potential drug
      interactions, and drug formulation. Seclusion or restraints are treatments of
      last resort due to safety issues. CONCLUSION: Compared with conventional
      antipsychotics (e.g., haloperidol), preliminary evidence indicates that atypical
      antipsychotics effectively reduce agitation, are better tolerated, and have fewer
      side effects. After an acute episode, atypical agents also help ease the
      transition from intramuscular to oral medication to promote ongoing treatment.

PMID- 16965192
TI  - Clinical perspectives on atypical antipsychotics for treatment of agitation.
AB  - In the past, the use of atypical antipsychotics in treating acute agitation was
      limited by a lack of data in behavioral emergencies and by the lack of
      intramuscular formulations or alternate rapid-acting oral formulations. This
      article evaluates current data from studies of atypical antipsychotics in
      agitated patients in both short- and long-term care settings. For patients with
      underlying psychosis, intramuscular atypical antipsychotics are effective and
      help ease the transition from intramuscular therapy in the acute care setting to
      oral dosing in inpatient or community settings. Evidence exists that atypical
      antipsychotics demonstrate antiagitation effects in schizophrenic patients for as
      long as 10 weeks and that overall clinical response may be partly mediated by
      these antiagitation properties. Intramuscular and oral atypical antipsychotics
      effectively treat acute agitation in both emergency and long-term care settings.
      For bipolar patients, these agents are valid therapeutic options for acute as
      well as longer-term alleviation of manic symptoms, including agitation. Safety
      concerns, however, limit their use in agitated elderly patients with dementia.

PMID- 16965193
TI  - Vagus nerve stimulation in patients with Alzheimer's disease: Additional follow
      up results of a pilot study through 1 year.
AB  - BACKGROUND: Cognitive-enhancing effects of vagus nerve stimulation (VNS) have
      been reported during 6 months of treatment in a pilot study of patients with
      Alzheimer's disease (AD). Data through 1 year of VNS (collected from June 2000 to
      September 2003) are now reported. METHOD: All patients (N = 17) met the National
      Institute of Neurological and Communicative Disorders and Stroke and the
      Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for
      probable AD. Responder rates for the Alzheimer's Disease Assessment Scale
      cognitive subscale (ADAS-cog) and Mini-Mental State Examination (MMSE) were
      measured as improvement or absence of decline from baseline. Global change,
      depressive symptoms, and quality of life were also assessed. Cerebrospinal fluid
      (CSF) levels for total tau, tau phosphorylated at Thr181 (phosphotau), and
      Abeta42 were measured by standardized enzyme-linked immunosorbent assay (ELISA).
      RESULTS: VNS was well tolerated. After 1 year, 7 (41.2%) of 17 patients and 12
      (70.6%) of 17 patients improved or did not decline from baseline on the ADAS-cog
      and MMSE, respectively. Twelve of 17 patients were rated as having no change or
      some improvement from baseline on the Clinician Interview-Based Impression of
      Change (CIBIC+). No significant decline in mood, behavior, or quality of life
      occurred during 1 year of treatment. The median change in CSF tau at 1 year was a
      reduction of 4.8% (p = .057), with a 5.0% increase in phosphotau (p = .040; N =
      14). CONCLUSION: The results of this study support long-term tolerability of VNS
      among patients with AD and warrant further investigation.

PMID- 16965194
TI  - Antecedents to panic disorder in nonreferred adults.
AB  - OBJECTIVE: Previous work has shown that childhood anxiety disorders are unique
      antecedents for panic disorder. The current study examined both childhood and
      adult comorbid disorders as potential antecedent disorders to panic disorder in a
      large sample of nonreferred adults. METHODS: Subjects were 1018 adults with (N =
      58) and without (N = 960) panic disorder who were derived from a sample
      originally ascertained through family studies of probands with and without
      attention-deficit/hyperactivity disorder (ADHD); data were obtained from 1988 to
      1996. Classification and regression trees (CART) analysis was used to examine
      anxiety and nonanxiety disorders antecedent to panic disorder. RESULTS: CART
      analysis showed that separation anxiety disorder, social phobia, and simple
      phobia were unique predictors of subsequent panic disorder. CONCLUSION: These
      results support and expand previously reported findings in referred samples
      documenting that comorbid anxiety disorders are unique antecedent risk factors
      for panic disorder.

PMID- 16965195
TI  - Overlap of anxiety and depression in a managed care population: Prevalence and
      association with resource utilization.
AB  - OBJECTIVE: To characterize the diagnosis of anxiety and depression within a large
      managed care population and to measure the impact of having both of these
      conditions on treatment patterns, health care utilization, and cost. Further, to
      compare the impact of having both conditions with having neither or either
      condition alone. METHOD: A retrospective, cross-sectional analysis of population
      level anxiety-related and depression-related utilization over a 12-month study
      period was conducted. Data were from the PharMetrics Patient-Centric database,
      which is composed of medical and pharmaceutical claims for approximately 36
      million patients from 61 health plans across the United States. Patients 18 years
      and older were included as cases in the analysis if they had a diagnosis of
      depression or anxiety during 2002. Four groups were identified based on the
      presence of anxiety and/or depression diagnosis: anxiety only, depression only,
      anxiety and depression, and controls. Controls were matched to the anxiety and
      depression cohort using a 4:1 ratio, based on patient age, gender, and similarity
      of health coverage. Cohorts were compared with respect to patient demographics,
      comorbid diagnoses, medication use, specialist care, utilization of health care
      services, and treatment costs, using both univariate and multivariate statistics.
      RESULTS: Significant differences in comorbid diagnoses, medication use, health
      care utilization, and treatment costs existed between the study groups.
      Specifically, patients with both anxiety and depression tended to have more
      somatic complaints such as abdominal pain, malaise, or chest pain than patients
      with either condition alone or the control group. Antidepressant use was highest
      among the anxiety and depression cohort, while anxiolytic use was as prevalent in
      the anxiety and depression cohort as in the anxiety only cohort. Patients in the
      anxiety only, depression only, or anxiety plus depression groups had a higher
      number of anxiety- and/or depression-related visits as well as visits not related
      to depression or anxiety than the control group, with the anxiety and depression
      cohort incurring the highest utilization of medical services. Similarly, in terms
      of cost, the disease cohorts incurred significantly higher cost than their
      control counterparts, with the anxiety and depression cohort incurring higher
      cost than those with either condition alone, even after accounting for
      differences in patient characteristics. CONCLUSIONS: Combination of anxiety and
      depression is fairly common in a managed care population as evidenced by
      diagnosis and treatment. The combination of both diagnoses appears to increase
      the complexity of these patients with respect to comorbid conditions as well as
      increases the economic cost to payers.

PMID- 16965196
TI  - A 1-year double-blind study of 2 doses of long-acting risperidone in stable
      patients with schizophrenia or schizoaffective disorder.
AB  - OBJECTIVE: This study examined the effects of 2 doses of long-acting risperidone
      injection in patients with schizophrenia or schizoaffective disorder. METHOD:
      This 52-week, prospective, randomized, double-blind, multicenter, international
      study included clinically stable outpatients with schizophrenia or
      schizoaffective disorder (DSM-IV criteria). Settings included physicians' offices
      and clinics. Patients received a fixed dose of long-acting risperidone (25 or 50
      mg) every 2 weeks. Primary outcome was time to relapse, defined as either re
      hospitalization or other exacerbation criteria. Other assessments included the
      Positive and Negative Syndrome Scale, Clinical Global Impressions-Severity of
      Illness scale, and functional and quality-of-life measures. Safety was assessed
      via treatment-emergent adverse events, laboratory tests, and movement disorder
      rating scales. Data were collected from December 2002 to September 2004. RESULTS:
      A total of 324 patients were randomized to 25 mg (N = 163) or 50 mg (N = 161) of
      long-acting risperidone. Time to relapse was comparable (p = .131) for both
      groups. Projected median time to relapse was 161.8 weeks (95% CI = 103.0 to
      254.2) with 25 mg and 259.0 weeks (95% CI = 153.6 to 436.8) with 50 mg. One-year
      incidences of relapse were 21.6% (N = 35) and 14.9% (N = 24), respectively (p =
      .059). Psychiatric hospitalization was the reason for relapse for 16 (10%) in the
      25-mg group and 10 (6%) in the 50-mg group. Patients experienced statistically
      significant but modest improvements at endpoint in most measures (i.e., psychotic
      symptoms, functioning, movement disorder severity) with both doses, with no
      significant between-group differences. CONCLUSION: In this 1-year study, long
      acting risperidone was associated with low relapse and rehospitalization rates,
      indicating that doses of 25 to 50 mg are appropriate for long-term treatment in
      schizophrenia.

PMID- 16965197
TI  - The effect of sudden clozapine discontinuation on management of schizophrenic
      patients: A retrospective controlled study.
AB  - BACKGROUND: The aims of our study were (1) to compare the dose of clozapine
      needed to achieve remission in patients who stopped their treatment (study group)
      versus patients who continued taking this medication (control group) and (2) to
      compare the clinical characteristics of remission between these 2 groups. METHOD:
      We retrospectively reviewed the medical records of all treatment-resistant
      schizophrenic and schizoaffective patients (according to DSM-IV criteria) who
      were treated with clozapine over a period of 9 years, from January 1995 through
      December 2003. The study group consisted of 43 patients and the control group of
      12 patients. All patients' files from both groups were examined, and each
      patient's remission was scored twice--initially on discharge from the hospital
      and subsequently after final discharge for the study group, or at the end of the
      study for the control group. RESULTS: The change of clozapine dose from the first
      to the last remission expressed by percentage shows a significant difference
      between the 43% increase in clozapine dose in the study group and the 12.5%
      decrease in clozapine dose in the control group (p < .001). Quality of remission
      assessment showed deterioration in the global remission score in the study group,
      while the quality of remission assessment in the control group did not show any
      change. CONCLUSIONS: Our findings suggest that the discontinuation of clozapine
      treatment leads to a deterioration in the quality of remission, with a need for
      an increased dose of clozapine. Further prospective studies on larger samples are
      needed to confirm these findings.

PMID- 16965198
TI  - The economic impact of bipolar disorder in an employed population from an
      employer perspective.
AB  - OBJECTIVE: To determine the economic impact of bipolar disorder on health benefit
      costs and health-related work absences from an employer perspective. METHOD: Data
      on health benefit costs and health-related absences during 2001 and 2002 were
      retrieved from a database and retrospectively examined. Regression modeling
      measured the cost differences while controlling for potentially confounding
      factors. The study population consisted of employees at multiple large employers
      who were widely dispersed throughout the United States. These employees were
      grouped into 2 cohorts: (1) employees with a bipolar disorder diagnosis (primary,
      secondary, or tertiary ICD-9 code of 296.0x, 296.1x, 296.4x, 296.5x, 296.6x,
      296.7x, or 296.8x) in 2001 and (2) employees with no bipolar disorder diagnosis
      during 2001 or 2002 (comparison cohort). Specific outcome measures included
      annual health benefit claim costs and salary-replacement payments for the
      following employee health benefits: health care insurance, prescription drug,
      sick leave, short- and long-term disability, and workers' compensation.
      Additional outcome measures included annual absence days due to workers'
      compensation, short- and long-term disability, and sick leave (separately).
      RESULTS: The analysis identified 761 employees (0.3%) with bipolar disorder and
      229,145 eligible employees without bipolar disorder. Employees with bipolar
      disorder annually cost $6836 more than employees without bipolar disorder (p <
      .05) and were more costly in every health benefit cost category. Employees with
      bipolar disorder missed an average of 18.9 workdays annually, while employees
      without bipolar disorder missed 7.4 days annually (p < .05). CONCLUSION: The
      impact of bipolar disorder can be costly in the workplace, leading to increased
      health benefit costs and increased absenteeism.

PMID- 16965199
TI  - Comorbidity of fibromyalgia and psychiatric disorders.
AB  - OBJECTIVE: To assess the co-occurrence of fibromyalgia with psychiatric disorders
      in participants of a fibromyalgia family study. METHOD: Patients (probands) with
      fibromyalgia, control probands with rheumatoid arthritis, and first-degree
      relatives of both groups completed a structured clinical interview and tender
      point examination. The co-occurrence odds ratio (OR) (the odds of a lifetime
      comorbid DSM-IV disorder in an individual with fibromyalgia divided by the odds
      of a lifetime comorbid disorder in an individual without fibromyalgia, adjusted
      for age and sex) was calculated; observations were weighted by the inverse
      probability of selection, based on the fibromyalgia status of the pro-band; and
      standard errors were adjusted for the correlation of observations within
      families. The study was conducted from September 1999 to April 2002. RESULTS: We
      evaluated 78 fibromyalgia pro-bands and 146 of their relatives, and 40 rheumatoid
      arthritis probands and 72 of their relatives. Among the relatives of both proband
      groups, we identified 30 cases of fibromyalgia, bringing the total number of
      individuals with fibromyalgia to 108, compared with 228 without fibromyalgia. The
      co-occurrence ORs for specific disorders in individuals with versus those without
      fibromyalgia were as follows: bipolar disorder: 153 (95% CI = 26 to 902, p <
      .001); major depressive disorder: 2.7 (95% CI = 1.2 to 6.0, p = .013); any
      anxiety disorder: 6.7 (95% CI = 2.3 to 20, p < .001); any eating disorder: 2.4
      (95% CI = 0.36 to 17, p = .36); and any substance use disorder: 3.3 (95% CI = 1.1
      to 10, p = .040). CONCLUSIONS: There is substantial lifetime psychiatric
      comorbidity in individuals with fibromyalgia. These results have important
      clinical and theoretical implications, including the possibility that
      fibromyalgia might share underlying pathophysiologic links with some psychiatric
      disorders.

PMID- 16965200
TI  - Recovery from depression predicts lower health services costs.
AB  - OBJECTIVE: To examine the association between outcome of acute-phase depression
      treatment and subsequent health services costs. METHOD: Data from 9 longitudinal
      studies of patients starting depression treatment were used to examine the
      relationship between outcome of acute-phase treatment and health services costs
      over the subsequent 6 months. All studies were 2- to 4-year studies conducted
      between the years 1991 and 2004. Assessment of diagnosis was done using the
      Inventory of Depressive Symptoms or the Structured Clinical Interview for DSM-IV.
      Clinical outcomes were assessed by structured telephone interviews using the
      Hamilton Rating Scale for Depression or a 20-item depression scale extracted from
      the Hopkins Symptom Checklist. Costs were assessed using health plan accounting
      records. RESULTS: Of 1814 patients entering treatment and meeting criteria for
      major depressive episode, 29% had persistent major depression 3 to 4 months
      later, 37% were improved but did not meet criteria for remission, and 34%
      achieved remission of depression. Those with persistent depression had higher
      baseline depression scores and higher health services costs before beginning
      treatment. After adjustment for baseline differences, mean health services costs
      over the 6 months following acute-phase treatment were 2012 dollars (95% CI =
      1832 dollars to 2210 dollars) for those achieving remission, 2571 dollars (95% CI
      = 2350 dollars to 2812 dollars) for those improved but not remitted, and 3094
      dollars(95% CI = 2802 dollars to 3416 dollars) for those with persistent major
      depression. Average costs for depression treatment (antidepressant prescriptions,
      outpatient visits, and mental health inpatient care) ranged from 429 dollars in
      the full remission group to 585 dollars in the persistent depression group.
      CONCLUSIONS: Among patients treated for depression in community practice, only
      one third reached full remission after acute-phase treatment. Compared with
      persistent depression, remission is associated with significantly lower
      subsequent utilization and costs across the full range of mental health and
      general medical services.

PMID- 16965201
TI  - Major depressive disorder, somatic pain, and health care costs in an urban
      primary care practice.
AB  - OBJECTIVE: To evaluate the extent to which pain severity contributes to the
      increased medical care costs associated with depression in primary care. METHOD:
      A systematic sample of primary care patients (N = 1028) from an urban practice
      were assessed between April 1, 2002, and January 16, 2003, with the DSM-IV
      Primary Care Evaluation of Mental Disorders Patient Health Questionnaire, the
      Sheehan Disability Scale, a medical illness checklist, and the Medical Outcomes
      Study 12-Item Short Form Health Survey, which includes a measure of pain
      interference with daily activities. Medical charges for inpatient, outpatient,
      and emergency department services were assessed for the 6-month periods preceding
      and following the index medical visit. Patients with and without major depressive
      disorder (MDD) were first compared with respect to clinical characteristics and
      median medical charges. Mean predicted medical care charges were then compared
      among 4 patient groups: (1) No MDD/ Low Pain Interference, (2) No MDD/High Pain
      Interference, (3) MDD/Low Pain Interference, and (4) MDD/High Pain Interference.
      RESULTS: As compared to patients without MDD (N = 821), those with MDD (N = 207)
      had significantly higher predicted mean medical care charges (19,838 dollars vs.
      6268 dollars; t = 3.3, p = .001) after controlling for age and gender and were
      significantly more likely to report at least moderate pain-related interference
      in daily activities (MDD: 69.1% vs. no MDD: 38.6%; chi 2 = 61.3, df = 1, p <
      .0001). Mean predicted medical care charges of patients with MDD and at least
      moderate pain-related interference were on average 2.33 times (95% CI = 1.34 to
      4.05) as high as those for patients with MDD and little or no pain-related
      interference. Among patients with at least moderate pain-related interference,
      MDD was associated with significantly greater mean predicted charges (mean =
      28,598 dollars/ year with MDD vs. 11,031 dollars/year without MDD). However,
      among patients with lower levels of pain-related interference, MDD was not
      associated with greater mean predicted medical charges (mean = 2306 dollars/year
      with MDD vs. 3560 dollars/year without MDD). CONCLUSION: In this urban primary
      care practice, major depressive disorder is associated with increased health care
      costs, but only among patients with moderate to extreme pain-related interference
      in daily activities.

PMID- 16965202
TI  - Association of PTSD and depression with medical and specialist care utilization
      in modern peacekeeping veterans in Canada with health-related disabilities.
AB  - OBJECTIVE: We examined the relative associations between posttraumatic stress
      disorder (PTSD) and depression severity with medical and specialist care use in
      modern peacekeeping veterans with health-related disabilities. METHOD: The
      participants consisted of 1016 male veterans who served in the Canadian Forces
      from 1990 to 1999, selected from a larger random sample of 1968 veterans who
      voluntarily completed an anonymous general health survey conducted by Veterans
      Affairs Canada in 1999. Survey instruments included the PTSD Checklist-Military
      Version (PCL-M), Center for Epidemiological Studies-Depression Scale, and
      questionnaires of health problems and service use, sociodemographic
      characteristics, and military history. RESULTS: Among peacekeeping veterans with
      health disabilities, "probable" PTSD (PCL-M score > or = 50) was associated with
      significantly more medical service use (primary and specialty care combined),
      with a mean of 16.4 times (SD = 17.4) compared with 6.0 times (SD = 6.6), p <
      .001, for veterans without PTSD. We found that in multivariate analyses, general
      medical care intensity (i.e., number of visits) was related to increased health
      problems, greater probable PTSD diagnosis, and greater depression symptom
      severity. We also found that depression severity accounted for health care use
      intensity and that PTSD only added a small amount of incremental variance above
      that. CONCLUSIONS: The observed association between PTSD (diagnosis and severity)
      and medical care utilization stresses the importance of PTSD screening in primary
      care settings, especially in patients with a history of military service. This
      association is also useful for clinicians and hospital administrators in
      understanding potential medical and psychiatric needs for military veterans.

PMID- 16965203
TI  - Reduced suicidal ideation in bipolar I disorder mixed-episode patients in a
      placebo-controlled trial of olanzapine combined with lithium or divalproex.
AB  - OBJECTIVE: To identify symptoms associated with suicidality in bipolar I disorder
      patients, and to assess suicide risk during treatment with olan-zapine in
      combination with lithium or divalproex. METHOD: We used data from a study
      (conducted from September 1997 to October 2000) in which DSM-IV bipolar I manic
      or mixed-episode patients who were partially responsive to at least 2 weeks of
      lithium or dival-proex monotherapy prior to study entry were randomly assigned to
      augmentation therapy with olanzapine (5-20 mg/day) or placebo. Among mixed
      episode patients with residual suicidality (Hamilton Rating Scale for Depression
      item 3 [HAM-D-3] score of 1 or above) at randomization to cotherapy, we
      identified items in the Young Mania Rating Scale, Positive and Negative Syndrome
      Scale, and Barnes Akathisia Rating Scale that correlated with HAM-D-3 scores. We
      used factor analysis of correlated items to identify symptom domains associated
      with suicidality ratings and assessed changes in symptom factors and HAM-D-3
      scores during 6 weeks of combination therapy with olanzapine versus placebo.
      RESULTS: In 58 mixed-episode patients, mean +/- SD HAM-D-3 scores averaged 1.36
      +/- 0.55 after at least 2 weeks of initial mood stabilizer monotherapy prior to
      study entry. Factors associated with the HAM-D-3 appeared to represent somatic
      discomfort, agitated depression, and psychotic features. Combination therapy with
      olanzapine (N = 36) versus placebo (N = 22) differentially reduced HAM-D-3 scores
      by 58% versus 29% (p < .05) within 1 week, and all 3 associated symptom factors
      within 2 weeks by averages of 31% versus 12% (p < .05). CONCLUSIONS: Suicidality
      in adult, mixed-episode, bipolar I disorder patients was associated with somatic
      discomfort, agitated depression, and psychosis. Overall, these findings suggest
      that the addition of an atypical antipsychotic-antimanic agent in some bipolar
      disorder patients may help to reduce suicidal ideation.

PMID- 16965204
TI  - Attenuation of antipsychotic-induced weight gain with early behavioral
      intervention in drug-naive first-episode psychosis patients: A randomized
      controlled trial.
AB  - BACKGROUND: The purpose of this study was to compare an early behavioral
      intervention (EBI) with nonstructured standard physical care (routine care
      intervention [RCI]) in preventing antipsychotic-induced weight gain in drug-naive
      first-episode psychosis patients. METHOD: Sixty-one patients with a DSM-IV
      diagnosed psychotic disorder were first randomly assigned to 3 different
      antipsychotic treatments (risperidone [N = 23], olanzapine [N = 18], and
      haloperidol [N = 21]) and subsequently randomly assigned to the intervention
      condition (EBI, N = 35) or RCI (N = 27). EBI was specifically designed to teach
      strategies to enhance control over factors associated with antipsychotic-induced
      weight gain and consisted of 8 flexible intervention modules that incorporated
      behavioral interventions, nutrition, and exercise. In the RCI group, patients
      were informed about potential weight gain and advised to increase their exercise
      and limit food intake. Body weight and body mass index were measured at baseline
      and then weekly for 3 months. In addition to change in weight and body mass
      index, a third outcome measure was the proportion of patients who had gained more
      than 7% of their body weight at 3 months. Participating patients were referred
      between August 2002 and September 2004. RESULTS: All 61 participants completed
      the study. Patients in the EBI group gained significantly less weight (mean = 4.1
      kg, SD = 4.0) than those allocated to the RCI group (mean = 6.9 kg, SD = 4.5) (p
      < .01) during the 3-month follow-up period. Similar findings were obtained when
      both groups were compared on treatment-induced change in body mass index, which
      was significantly less in the EBI group than in the RCI group (1.40 vs. 2.39
      kg/m2) (p < .01). Accordingly, significantly fewer patients in the EBI group (N =
      11; 39.3%) than in the RCI group (N = 26; 78.8%) (p < .002) increased their
      baseline weight by more than 7%, the cutoff for clinically meaningful weight
      gain. CONCLUSIONS: EBI was effective in attenuating antipsychotic-induced weight
      gain in a drug-naive first-episode psychosis cohort. Patients displayed good
      adherence to this type of preventive intervention.

PMID- 16965205
TI  - Concomitant medications may not improve outcome of antipsychotic monotherapy for
      stabilized patients with nonacute schizophrenia.
AB  - BACKGROUND: There are virtually no controlled data suggesting that concomitant
      psychotropic medications (CPMs) improve outcome in schizophrenia after the acute
      phase. Despite that, polypharmacy (with all of its disadvantages) is far more
      common than monotherapy. To our knowledge, there have been no published reports
      of prospective systematic investigations of the efficacy of unrestricted CPM use
      in nonacute schizophrenia. METHOD: This was a naturalistic, systematic study
      using a sample of 53 stabilized patients with DSM-IV-TR schizophrenia from 1
      clinical practice setting including both private patients and patients from
      controlled research studies of the effectiveness of antipsychotics. Since there
      are meager controlled or systematic data on the effectiveness of CPM use with
      antipsychotics in nonacute schizophrenia, we tested the clinical strategy of CPM
      use by gradually tapering all CPMs (except antianxiety agents). The aim was to
      determine if the CPM improved outcome, had no effect, or worsened outcome using
      the Clinical Global Impressions-Improvement scale before and after taper, over at
      least 3 months and in some cases up to 18 months after discontinuation. Data were
      gathered from July 2002 to June 2005. RESULTS: For 21 patients undergoing 22
      antidepressant tapers, no change was noted in 18 of 22 tapers, while in 3
      improvement was noted and in 1 worsening was noted. For the 12 patients on
      treatment with mood stabilizers, no change was noted in 10 of 13
      discontinuations, while in 3 mild worsening was noted. One patient was on
      treatment with both modafinil and trazodone and reported no change after tapering
      each in separate discontinuation trials, while another 3 patients were taking
      sleeping medications and also noted no change after discontinuation. CONCLUSION:
      For most stabilized, chronic patients with schizophrenia, tapering adjunctive
      medications did not change outcome. This naturalistic study further defines the
      limits of efficacy of some concomitant classes of medications in patients with
      chronic schizophrenia who are already receiving adequate antipsychotic therapy.

PMID- 16965206
TI  - Outcome of a 4-step treatment algorithm for depressed inpatients.
AB  - OBJECTIVE: The aim of this study was to examine the efficacy and the feasibility
      of a 4-step treatment algorithm for inpatients with major depressive disorder.
      METHOD: Depressed inpatients, meeting DSM-IV criteria for major depressive
      disorder, were enrolled in the algorithm that consisted of sequential treatment
      steps (washout period, anti-depressant monotherapy, lithium addition, treatment
      with a nonselective monoamine oxidase inhibitor, electroconvulsive therapy).
      Definition of nonresponse and progression through the steps of the algorithm was
      dependent on the score on the 17-item Hamilton Rating Scale for Depression (HAM
      D) at predefined evaluation times. Patients were admitted from April 1997 through
      July 2001. RESULTS: Of the 203 patients studied, 149 were treated according to
      the full algorithm, and 54 patients were immediately entered into step 3. Of the
      203 patients, 165 (81%) achieved response (> or = 50% reduction in HAM-D score)
      and 101 (50%) remitted (final HAM-D score < or = 7). Of the 149 patients treated
      according to the full algorithm, 129 (87%) responded and 89 (60%) remitted.
      Twenty-four patients (16%) dropped out from the algorithm. CONCLUSION: Although
      response with antidepressant monotherapy was less than 50%, successive treatment
      according to the 4-step algorithm was very effective in a sample of depressed
      inpatients. The adherence to the algorithm was good as shown by a low dropout
      rate. This study emphasizes the importance of persisting with standardized
      antidepressant treatment in patients who are initially nonresponders to the first
      antidepressant. By the end of the study, more than 80% of the patients responded
      and 50% achieved full remission.

PMID- 16965207
TI  - Relapse of aggressive and disruptive behavior in mentally retarded adults
      following antipsychotic drug withdrawal predicts psychotropic drug use a decade
      later.
AB  - BACKGROUND: Mental retardation is frequently associated with aggression toward
      self and others. Antipsychotic medications are frequently used as a major
      treatment of such aggression. However, national and state policies and guidelines
      are weighted toward stopping or decreasing the doses of these medications
      whenever possible, although exceptions are permitted. The purpose of this study
      was to determine if relapse during or after antipsychotic drug withdrawal in
      mentally retarded adults predicts continuing antipsychotic drug use an average of
      a decade later. METHOD: We report here on a 6- to 13-year (average 10-year)
      follow-up of 151 institutionalized mentally retarded adults. During the period
      1990-1997, the subjects had been prescribed antipsychotic medications to treat
      maladaptive behaviors, primarily consisting of aggression, disruptive/destructive
      behaviors, or a combination of these. We compared subjects' psychotropic
      medication profiles in 2003 as they related to outcome during the earlier period.
      Our goal was to determine if rapid relapse (a clinically significant increase in
      maladaptive target symptoms, beginning 3 months or less after antipsychotic drug
      termination or dosage reduction, that was reversed by antipsychotic drug
      reinstitution or dosage increases) during or after routine withdrawal of an
      antipsychotic predicted psychotropic drug use in 2003. RESULTS: For those
      individuals successfully withdrawn from antipsychotic medications, 66.3% (55/83)
      were still psychotropic drug free in 2003. For those who rapidly relapsed during
      the period 1990-1997 following antipsychotic drug withdrawal or dosage decreases,
      only 9.0% (5/55) were psychotropic medication free in 2003. CONCLUSION: These
      observations support policies and guidelines indicating that attempts to stop
      treatment with antipsychotic medications in mentally retarded individuals are
      worthwhile. However, the results also indicate that eventual discontinuation of
      antipsychotic medications in institutionalized mentally retarded adults who have
      previously relapsed upon such withdrawal is unlikely to be successful. Rigid
      adherence to drug withdrawal policies and guidelines in such individuals should
      be reconsidered.

PMID- 16965209
TI  - Exposure to mirtazapine during pregnancy: a prospective, comparative study of
      birth outcomes.
AB  - BACKGROUND: Mirtazapine is a novel piperazinoazepine antidepressant, unrelated to
      any known class of antidepressants. Currently, apart from a few case reports and
      case series in the literature, there are no studies evaluating the safety of this
      drug during pregnancy. OBJECTIVE: To determine whether mirtazapine increases the
      risk for major malformations in newborns when used by pregnant women. METHOD: The
      study design was prospective, with 2 comparison groups: disease-matched pregnant
      women diagnosed with depression taking other antidepressants and pregnant women
      exposed to nonteratogens. The primary outcome was major malformations in
      neonates; secondary endpoints included spontaneous abortions, therapeutic
      abortions, gestational age at birth, and mean birth weight. Women were recruited
      from 5 teratogen information services in Toronto, Canada; Farmington, Conn.,
      U.S.A.; Jerusalem, Israel; Rome, Italy; Sydney, Australia; and from the Drug
      Safety Research Unit in Southampton, United Kingdom. Women were recruited into
      the study from June 2002 to August 2005. RESULTS: We were able to follow 104
      pregnancy outcomes in each drug group. There were 77 live births, 1 stillbirth,
      20 spontaneous abortions, 6 therapeutic abortions, and 2 major malformations in
      the mirtazapine group. The mean +/- SD birth weight was 3335 +/- 654 g and the
      mean +/- SD gestational age at delivery was 38.9 +/- 2.5 weeks. Most (95%) of the
      women took mirtazapine in the first trimester, but only 25% of the women took it
      throughout pregnancy. The differences among the 3 groups were in the rate of
      spontaneous abortions, which was higher in both antidepressant groups (19% in the
      mirtazapine group and 17% in the other antidepressant group) than in the
      nonteratogen group (11%), but none of the differences were statistically
      significant. The rate of preterm births (prior to 37 weeks' gestation) was also
      higher in the mirtazapine group (10%) and in the other antidepressant group (7%)
      than in the nonteratogen group (2%). The difference was statistically significant
      between the mirtazapine group and the nonteratogen group (p = .04). CONCLUSION:
      Mirtazapine does not appear to increase the baseline rate of major malformations
      of 1% to 3%. However, the higher number of spontaneous abortions in the
      antidepressant groups confirms the higher rates of spontaneous abortions in
      pregnant women taking antidepressant medications found in previous studies.

PMID- 16965210
TI  - Anxiety disorders during pregnancy and the postpartum period: A systematic
      review.
AB  - OBJECTIVE: The postpartum period is recognized as a time of vulnerability to
      affective disorders, particularly postpartum depression. In contrast, the
      prevalence and clinical presentation of anxiety disorders during pregnancy and
      the postpartum period have received little research attention. In this article,
      we review the medical literature as it relates to the prevalence and clinical
      presentation of panic disorder, obsessive-compulsive disorder, posttraumatic
      stress disorder, and generalized anxiety disorder during pregnancy and the
      postpartum period. DATA SOURCES: MEDLINE (1966 to July 2005 week 1) and PsycInfo
      (1840 to July 2005 week 1) were searched using combinations of the following
      search terms: pregnancy, childbirth, postpartum, panic disorder, phobia,
      obsessive-compulsive disorder, posttraumatic stress disorder, and generalized
      anxiety disorder. STUDY SELECTION: All relevant papers published in English and
      reporting original data related to perinatal anxiety disorders were included.
      DATA EXTRACTION: Studies were examined for data related to the prevalence,
      presentation, predictors/risk factors, new onset, course, and treatment of
      anxiety disorders during pregnancy and the postpartum period. DATA SYNTHESIS:
      Anxiety disorders are common during the perinatal period, with reported rates of
      obsessive-compulsive disorder and generalized anxiety disorder being higher in
      postpartum women than in the general population. The perinatal context of anxiety
      disorders presents unique issues for detection and management. CONCLUSIONS:
      Future research is needed to estimate the prevalence of perinatal anxiety
      disorders more precisely, to identify potential implications of maternal anxiety
      disorders for maternal quality of life and child development, and to determine
      safe and effective treatment methods.

PMID- 16965211
TI  - Pilot randomized controlled trial of interpersonal counseling for subsyndromal
      depression following miscarriage.
AB  - OBJECTIVE: Miscarriage, which occurs in 10% to 20% of clinically recognized
      pregnancies, is associated with an increased risk for subsyndromal depression. We
      examined whether Interpersonal Counseling (IPC) was superior to treatment as
      usual (TAU) in reducing subsyndromal depression among miscarrying women and,
      secondarily, superior to TAU in improving role functioning. METHOD: Nineteen of
      20 eligible women participated in a randomized controlled trial of 1 to 6 weekly
      telephone sessions of IPC versus TAU, which consisted of whatever lay counseling
      or professional care women sought on their own initiative, from October 2001 to
      April 2002. The 2 trial arms were compared on mean within-subject change in
      Hamilton Rating Scale for Depression-17-item (HAM-D-17) scores and in role
      functioning scale scores (a 5-item modification of the 36-item Medical Outcomes
      Study questionnaire) from baseline to post-intervention. RESULTS: In the primary
      intent-to-treat analysis, the baseline mean HAM-D-17 scores were 18.0 (SD +/-
      8.4) and 14.8 (SD +/- 6.6) in the IPC (N = 10) and TAU (N = 9) arms,
      respectively; post-intervention, the corresponding means were 11.6 (SD +/- 8.2)
      and 12.9 (SD +/- 8.3). The mean within-subject decline in HAM-D-17 scores was
      significantly greater in the IPC (6.4) than in the TAU (1.9) arm (difference in
      mean within-subject score decline, adjusted for design features, baseline HAM-D
      17 scores and for baseline ethnic imbalance between study arms, 6.2 [95% CI = 0.4
      to 12.0]). In a subordinate completers' analysis (N = 15), the corresponding mean
      decline and difference in adjusted mean decline were 8.0, 2.4, and 6.7 (95% CI =
      0.4 to 13.1), respectively. Treatment was unrelated to improved role functioning.
      CONCLUSION: The efficacy of telephone-administered IPC for subsyndromal
      depression after miscarriage warrants testing in a full-scale randomized
      controlled trial.

PMID- 16965212
TI  - FDA post-marketing safety decisions.

PMID- 16965213
TI  - Sedative effects of low-dose risperidone in GAD patients and risk of drug
      interactions.

PMID- 16965214
TI  - Reversal of antipsychotic-induced hyperprolactinemia, weight gain, and
      dyslipidemia by aripiprazole: A case report.

PMID- 16965216
TI  - A case of probable bipolar VI disorder?

PMID- 16965217
TI  - Initial dosing strategies for long-acting injectable risperidone.

PMID- 16965218
TI  - Aripiprazole augmentation of venlafaxine in the treatment of psychogenic
      excoriation.

PMID- 16965219
TI  - What interventions do South African qualified doctors think will retain them in
      rural hospitals of the Limpopo province of South Africa?
AB  - INTRODUCTION: In South Africa, the health system faces a variety of problems,
      such as an overall shortage of and misdistribution of healthcare workers. The
      Department of Health in South Africa has attempted to address the shortage of
      rural doctors by introducing various interventions, including an increase in
      salaries, introduction of scarce skills and rural allowances, the deployment of
      foreign doctors, and upgrading of clinics and hospitals. Despite these, the
      maldistribution of doctors working in South Africa has not improved
      significantly. This attests to the multifactorial nature of this problem and to
      the fact that intensive and sustained efforts are needed to rectify it. Few South
      African studies have been undertaken to establish the needs of rural doctors in
      South Africa and to seek possible solutions to their problems. While a number of
      studies have identified some of the major problems, much still needs to be done.
      Innovative ways to address this crisis are urgently needed. The main objectives
      of this study were to identify interventions as proposed by doctors in the rural
      Limpopo province of South Africa and to develop recommendations based on these.
      METHODS: This study utilised a descriptive qualitative design using a semi
      structured questionnaire. Ten doctors from rural hospitals within all six
      districts of the Limpopo province were randomly selected and interviewed.
      RESULTS: Themes recommended included: increasing salaries and rural allowances;
      improving rural hospital accommodation; ensuring career progression; providing
      continuing medical education; increasing support by specialist consultants;
      improving the physical hospital infrastructure and rural referral systems;
      ensuring the availability of essential medical equipment and medicines;
      strengthening rural hospital management and increasing the role of doctors in
      management; improving the working conditions; establishing private-public
      collaborations with private general practitioners; increasing rural doctors'
      leave allocations; ensuring adequate senior support for junior doctors; improving
      rural hospital environments and providing recreational facilities; assisting
      rural doctors' families, and providing recognition and appreciation for the work
      rural doctors do. CONCLUSION: The resolution of one isolated factor without
      improving the host of push factors currently present in the health system is
      unlikely to lead to significant improvements in the retention of rural doctors.
      The results of this study can be used to assist the Limpopo Department of Health
      to identify the most pressing needs of rural doctors in the province. A number of
      interventions are suggested by rural doctors that they feel would retain them in
      their current rural practices. The recommendations include various interventions
      involving different levels of the healthcare system. It also recommends an
      incentive package for doctors willing to serve longer term in rural hospitals.

PMID- 16965220
TI  - Non-selective fetal reduction is malpractice.
AB  - Non-selective multifetal pregnancy reduction is carried out to reduce healthy
      higher order multiple fetuses to one or two fetuses. No studies exist to show any
      benefit of this practice and a Cochrane review, as well as investigators in the
      field, have not found any justification for such practice. From a medical point
      of view, this non evidence-based practice is not following good clinical
      practice. Any practice that transfers more than one or two embryos, for instance
      due to commercial interests, should be abandoned by the international medical
      community because multifetal pregnancies can, to a large extent, be avoided by
      transferring only one or a maximum of two fertilized eggs by in vitro
      fertilization. Further, ovarian stimulating programs should strictly adhere to
      protocols aiming at mono-ovulation.

PMID- 16965221
TI  - Guidelines for the management of spontaneous preterm labor.
AB  - Preterm birth is defined as delivery at <37 completed weeks of pregnancy (World
      Health Organization). Spontaneous preterm birth (SPB) includes preterm labor,
      preterm spontaneous rupture of membranes, preterm premature rupture of membranes
      (PPROM) and cervical weakness; it does not include indicated preterm delivery for
      maternal or fetal conditions. Early SPB (<32 weeks' gestation) is associated with
      an increased higher perinatal mortality rate, inversely proportional to
      gestational age. The pathophysiologic events that trigger SPB are largely unknown
      but include decidual hemorrhage (abruption), mechanical factors (uterine
      overdistention or cervical incompetence), and hormonal changes (perhaps mediated
      by fetal or maternal stress). In addition, several cervicovaginal infections have
      been associated with preterm labor. SPB is also the leading cause of long-term
      morbidity, including neurodevelopmental handicap, cerebral palsy, seizure
      disorders, blindness, deafness and non-neurological disorders, such as
      bronchopulmonary dysplasia and retinopathy of prematurity. Delaying delivery may
      reduce the rate of long-term morbidity by facilitating the maturation of
      developing organs and systems. The benefits of administration of antepartum
      glucocorticosteroids to reduce the incidence and severity of respiratory distress
      syndrome may be exploited by delay. Delay may also permit transfer of the fetus
      in utero to a center with neonatal intensive care unit facilities. There is
      considerable variation in the way that spontaneous preterm labor (SPTL) is
      diagnosed, managed and treated internationally. The development of clinical
      guidelines requires an evidence-based approach to improve outcome and allow more
      efficient use of resources. With recent advances in our understanding of the
      etiology and mechanisms of SPTL and the availability of safer, more specific
      tocolytics, it was felt that guidelines should be developed to achieve, if
      possible, an European consensus in patient diagnosis, management and treatment.

PMID- 16965222
TI  - Accuracy of second trimester fetal head circumference and biparietal diameter for
      predicting the time of spontaneous birth.
AB  - AIMS: Previous studies suggested that head circumference (HC) predicts the date
      of confinement better than the biparietal diameter (BPD). The present study aimed
      to prospectively test this assumption. METHODS: A prospective study including
      4179 consecutive women attending the second trimester routine ultrasound
      examination at 17-20 weeks of gestation. Outer-outer BPD and HC were determined
      as the average of three repeated measurements. Twins were excluded. Time of
      delivery was noted, the differences between this and the predicted date of
      delivery calculated with HC and BPD (based on a pregnancy duration of 282 days),
      and the two methods were compared using Wilcoxon signed rank test. RESULTS: For
      the entire group, the median differences between actual and predicted delivery
      with HC and BPD were 0.9 and 1.2 days, respectively. For deliveries with a
      spontaneous onset of labor (n=3336) the corresponding differences were 0.9 and
      1.4 days. The difference between the HC and BPD methods was significant
      (P<0.0001). In the group of spontaneous onset of labor, there were 05.6% post
      term pregnancies (>or=296 days) according to HC and 5.7% according to BPD.
      CONCLUSION: Provided that the expected pregnancy duration was 282 days, both HC
      and BPD predicted spontaneous birth with a mean accuracy of one day, HC being
      significantly better than BPD.

PMID- 16965223
TI  - The association between maternal cervicovaginal proinflammatory cytokines
      concentrations during pregnancy and subsequent early-onset neonatal infection.
AB  - OBJECTIVE: The aim of this study was to investigate the relationship between the
      concentration of selected proinflammatory cytokines (IL-1alpha, IL-1beta, IL-6
      and IL-8) in cervicovaginal fluid, as measured in midgestation, and the risk of
      early-onset neonatal infection (EONI). METHOD: Cervicovaginal fluids were
      obtained from a cohort of 114 pregnant women at 22 to 34 weeks' gestation. The
      samples were analyzed for the concentrations of selected proinflammatory
      cytokines using standard enzyme-linked immunosorbent assay technique (ELISA).
      Lower genital tract microbiology was diagnosed using Gram stain method according
      to Spiegel's criteria and by culture. RESULTS: Mean gestational age at the time
      of sampling was 29.0 weeks. Mean time between sampling and delivery was 9.3 (SD
      4.7) weeks. Bacterial vaginosis (BV) was diagnosed in 27.2% of subjects and M.
      hominis and U. urealyticum in 22.8% and 26.3%, respectively. Out of 114 women
      examined, 20 (17.5%) delivered newborns with EONI. Median cervicovaginal
      concentrations of IL-1alpha, IL-1beta, IL-6 and IL-8 did not differ between women
      who delivered newborns with EONI as compared to women who delivered newborns
      without EONI. Women with pathological lower genital tract microflora and low IL-8
      concentration (below 25(th) percentile) during pregnancy presented a significant
      risk of delivering newborns with EONI (OR=4.9; 95% CI, 1.1-22.8). Subjects with
      pathological lower genital tract microflora and a low concentration of more than
      one cytokine had the highest risk of delivering a newborn with EONI, OR=16.2, 95%
      CI, 1.1-234.0. CONCLUSIONS: Cytokine measurement in cervicovaginal fluid in early
      gestation could be useful for predicting subsequent EONI only among pregnant
      women with lower genital tract infection. Maternal genital tract immune
      hyporesponsiveness as represented by low concentrations of proinflammatory
      cytokines may create a permissive environment for ascending infection and may
      lead to subsequent EONI.

PMID- 16965224
TI  - Leukocytosis might precede in-hospital eclampsia in preeclamptic women who do not
      receive magnesium sulfate.
AB  - In an effort to better define preeclamptic women at risk of eclampsia, we
      examined the predictive value of maternal demographic characteristics and
      admission maternal laboratory values for the risk of subsequent development of
      eclampsia in preeclamptic women, who were not receiving magnesium sulfate during
      hospitalization. The decision to use magnesium sulfate prophylaxis was at the
      discretion of the treating physician. Preeclamptic women admitted throughout a 3
      year period and treated with a protocol exempting magnesium sulfate therapy were
      retrospectively included (n=497). Maternal data at admission were recorded and
      analyzed. Eight women developed an eclamptic seizure during subsequent hospital
      follow-up. Logistic regression models were used to assess the independent
      predictive role of each variable on the development of eclampsia. Lower serum
      fibrinogen values, increased leukocyte counts, and increased diastolic blood
      pressure at admission were independent predictors of a subsequent in-hospital
      eclamptic seizure. An initial diastolic blood pressure >or=120 mm Hg, blood
      leukocyte count >16,000/microL, and serum fibrinogen value <450 mg/dL were
      associated with a 25.4-, 7.1-, and 26.6-fold increased risk of eclampsia,
      respectively. We conclude that marked leukocytosis and diastolic blood pressure
      increment might precede the development of eclampsia. Serum fibrinogen
      concentrations >450 mg/dL seem to be protective for eclampsia. The association
      between inflammation and eclampsia merits further investigation.

PMID- 16965225
TI  - Randomized prospective comparative study of ursodeoxycholic acid and S-adenosyl-L
      methionine in the treatment of intrahepatic cholestasis of pregnancy.
AB  - AIM: To compare the efficacy of the ursodeoxycholic acid (UDCA) and S-adenosyl-L
      methionine (SAMe) monotherapy with their combined effect on intrahepatic
      cholestasis of pregnancy (ICP). PATIENTS AND METHODS: We studied singleton
      pregnancies at <36 weeks with a moderate or severe form of ICP between January
      1999 and March 2004. Patients were randomized to either oral UDCA 3x250 mg daily
      or 500 mg SAMe twice daily in slow running infusion for twelve days followed by
      oral administration of 500 mg twice daily until delivery. Intensive
      hematological, biochemical and fetal monitoring were carried out. RESULTS: Of the
      78 women enrolled, 25 received SAMe monotherapy, 26 received UDCA, and 27
      received combined therapy. Groups were initially comparable in terms of
      gestational age, duration of therapy, parity and biochemical characteristics. All
      therapies improved the pruritus. The combined therapy and the monotherapy with
      UDCA (later) led to improving of the serum concentrations of bile acids and
      transaminases compared with SAMe monotherapy (P<0.01). Combined therapy led to a
      faster decrease of serum concentrations of bile acids and transaminases compared
      with UDCA monotherapy (borderline significance). Gestational ages were similar in
      all groups. No adverse effects were noted on the fetuses or neonates with either
      therapy. CONCLUSIONS: UDCA is an effective drug in the treatment of ICP, and
      combined with SAMe, has probably a synergistic effect on biochemical parameters.
      This mode of treatment seems more effective but the effect of the successful
      treatment on the fetus is unclear. Therefore, the ante- and intrapartum
      monitoring of the fetus should be part of the management of severe forms of ICP.
      The project is supported by IGA MZ CR (No. NH/7376-3).

PMID- 16965226
TI  - Coagulation-fibrinolysis is more enhanced in twin than in singleton pregnancies.
AB  - AIMS: To examine whether coagulation-fibrinolysis in late pregnancy in women with
      twin pregnancies is more pronounced than in women with singleton pregnancies.
      PATIENTS AND METHODS: The plasma levels of D-dimer, fibrinogen/fibrin degradation
      products (FDP), and fibrinogen, the platelet count, and the antithrombin activity
      were assessed from 3 weeks before delivery until postpartum day 7 in 48 women (24
      singleton and 24 twin pregnancies) without preeclampsia who underwent cesarean
      sections. RESULTS: Women with singleton or twin pregnancies gave birth at 37.3+/
      1.2 weeks or 35.2+/-1.4 weeks, respectively. Compared with singleton mothers,
      prenatal D-dimer and FDP levels were consistently and significantly higher among
      women with twin pregnancies. A significantly larger proportion of twin mothers
      exhibited prenatal levels of D-dimer >5.0 microg/mL, FDP >10.0 microg/mL,
      fibrinogen <420 mg/mL and antithrombin activity <70%. In addition, prenatal
      antithrombin activity in plasma was significantly lower. CONCLUSIONS: Coagulation
      fibrinolysis is more enhanced in women with twin gestation than in women with
      singleton gestation.

PMID- 16965227
TI  - Fetal behavior analyzed by ultrasonic actocardiogram in cases with central
      nervous system lesions.
AB  - AIMS: This study examined whether analysis of fetal behavioral states by
      monitoring fetal heart rate and movement using an actocardiogram (ACG), could
      provide prognostic information related to fetal central nervous system (CNS)
      lesions. METHODS: The ACG simultaneously records fetal heart rate (FHR) and fetal
      movement bursts composed of spikes of ultrasonic Doppler signals. Durations of
      FHR accelerations and fetal movement bursts were measured manually. Five
      actocardiographic indices were studied in 12 fetuses with CNS lesions and in 14
      normal pregnancies of 28-38 weeks. RESULTS: Severity of the fetal CNS lesions was
      estimated from the acceleration/burst (A/B) duration ratio, which correlated with
      the rank of the sonographic fetal functional test in cases with CNS lesions.
      Severity of a fetal lesion may also be estimated by the regression equation of
      the A/B duration ratio and behavioral ranking. CONCLUSION: The severity of fetal
      CNS lesions may be estimated by quantitative analysis of ACG usings the
      measurement of A/B duration ratio to provide a prognosis. An ACG may demonstrate
      a loss of CNS control in cases with severe brain damage.

PMID- 16965228
TI  - Early weight gain does not decrease the incidence of low birth weight and small
      for gestational age triplets in mothers with normal pre-gestational body mass
      index.
AB  - OBJECTIVE: To examine if the recommended weight gain of >680 g/week during the
      first 24 weeks of pregnancy decreases the frequency of adverse birth weight
      outcomes in triplet mothers with a normal pregravid BMI. STUDY DESIGN:
      Retrospective observational study of a large sample of triplet mothers with a
      normal (19.8-26) pregravid BMI. Adequate, average, and inadequate weight gains
      were defined as >680, 500-680, and <500 g/week. Outcome measures were the
      incidence of >or=1 SGA infant and total triplet birth weight <4500 g. RESULTS: Of
      the 1166 triplet mothers, 208 (17.8%) gained >680 g/week during their pregnancy.
      This presumed adequate weight gain did not reduce the incidence of SGA triplets
      or that of total birth weight <4500 g, irrespective of parity. These adverse
      birth weight outcomes were 2 to 3.5 times lower among multiparous compared to
      nulliparous mothers. CONCLUSION: Early weight gain of >680 g/week in triplet
      mothers with a normal pre-pregnancy BMI is not associated with a decrease in the
      incidence of adverse outcomes. Weight gain recommendations in triplet pregnancies
      should be realistic and associated with a low risk-benefit ratio.

PMID- 16965229
TI  - Umbilical artery pulsatility index: reliability at different sampling sites.
AB  - OBJECTIVES: To analyse the inter-observer and inter-artery reliability of the
      umbilical artery (UA) pulsatility index (PI) at different sampling sites.
      METHODS: One hundred consecutive singleton pregnancies between 24 and 40 weeks
      were included. The PI was calculated by two independent operators from both
      umbilical arteries at the placental end, at a free-floating loop and at the
      perivesical segment. Reliability analyses were performed between observers and
      between arteries at each sampling site. RESULTS: The mean percentage of PI
      difference between arteries was 15.2, 14.5 and 22% at the placental end, free
      loop and perivesical site, respectively. The Intraclass correlation coefficients
      at each site were 0.51, 0.59 and 0.67, respectively. Whereas about 20% of cases
      showed a percentage of PI difference between arteries greater than 20% at free
      loop and placental end sites, and at the perivesical site this figure was 45%.
      CONCLUSIONS: The perivesical sampling site for UA PI calculation is more reliable
      than at a free-floating loop, albeit without significance, and is significantly
      more reliable than at the placental end of the umbilical cord. Since discordances
      in PI between both arteries are more pronounced at the perivesical site, it seems
      mandatory to evaluate both arteries in this segment.

PMID- 16965230
TI  - Inferior vena cava diameter pulse waveforms in the human fetus: relationship with
      flow velocity waveform.
AB  - Our purpose was to evaluate the hemodynamic significance of fetal inferior vena
      cava (IVC) flow velocity waveform indices during fetal development in relation to
      the diameter pulse waveform. Doppler ultrasound and a phase locked loop echo
      tracking system were used to measure flow velocity waveform and diameter pulse
      waveform, respectively. Twenty-seven normal singleton pregnancies were examined
      from 20 weeks until term at 4-week intervals. The diameter pulse waveform
      consisted of four waves (A, X, V, and Y waves). The A value (end-diastolic
      diameter) was associated with the end-diastolic pressure, which causes reverse
      flow during right atrial contraction. In normal fetuses, a weight-related lower
      end-diastolic diameter suggested that the end-diastolic pressure was decreased.
      Except for a positive correlation between the percent reverse flow during atrial
      contraction and the A value per unit fetal weight, no correlations were found
      between diameter waveform indices and blood flow velocity waveform indices. The
      peak velocity index of the velocity waveform significantly correlated with the
      umbilical artery flow velocity waveform systolic/diastolic ratio. The fetal IVC
      velocity waveform indices did not yield unequivocal information as to changes in
      central venous pressure, for which purpose the diameter pulse waveform analysis
      would seem to be the only available method.

PMID- 16965231
TI  - A trial of preventing early- and late-onset Group B streptococcal sepsis with
      combined intrapartum chemoprophylaxis and universal neonatal screening.
AB  - BACKGROUND: Prevention of early-onset Group B Streptococcal (GBS) infection has
      been attempted by employing universal maternal screening for GBS, intrapartum
      chemoprophylaxis, and a single dose of penicillin given to neonates in the first
      hour of life. This strategy, however, does not seem to prevent the occurrence of
      late-onset neonatal group B streptococcal disease. STUDY DESIGN: We assessed
      early and late-onset GBS disease with the use of a before-after study designed to
      evaluate the implementation of intrapartum antimicrobial prophylaxis. Moreover,
      universal neonatal screening for colonization of GBS was carried out with swabs
      of the external ear canal. Newborns with GBS colonization received a preventive
      treatment with oral amoxicillin for 10 days. RESULTS: Early-onset GBS infection
      decreased from 0.5 per thousand at baseline period to 0.19 per thousand at the
      study period. The incidence of late-onset GBS disease decreased from 1:1348 (0.74
      per thousand) to 1:20,710 (0.048 per thousand). The overall cost for universal
      neonatal screening paid for by the Italian Health System in the study period was
      31,065 US dollars with an antibiotic prophylaxis cost of 2,399 US dollars.
      CONCLUSIONS: A combined strategy based on GBS culture screening and assessment of
      risk factors for perinatal GBS disease can significantly reduce the rate of both
      early and late-onset GBS infections.

PMID- 16965232
TI  - Impact of prenatal urinomas in patients with posterior urethral valves and
      postnatal renal function.
AB  - OBJECTIVE: Posterior urethral valves (PUV) are a common cause of lower urinary
      tract obstruction. Renal failure occurs in approximately one third of the cases.
      It is debated whether urinoma formation is a protective mechanism to reduce
      pressure-related impairment of renal function. The aim of our study was to
      determine if urinoma formation is able to preserve renal function on the side of
      the urinoma. METHODS: Five male patients diagnosed with posterior urethral valves
      and uni- or bilateral urinoma formation were reviewed. Renal function was
      assessed by serum creatinine level at days 4-7 and at two months, in addition to
      dimercaptosuccinylacid (DMSA) scintigraphy at 4-6 weeks postnatal age. RESULTS:
      Impaired renal function occurred unilaterally in four patients, two had bilateral
      urinoma formation, and the other two boys presented with unilateral urinoma, one
      with preserved renal function ipsilateral to the urinoma and the other on the
      contralateral side. Urinary ascites was detected in three patients, all underwent
      antenatal centesis. CONCLUSIONS: No association was found between renal function
      and urinoma formation in patients with PUV.

PMID- 16965235
TI  - Estimated Asian adult soy protein and isoflavone intakes.
AB  - There is substantial interest in the possible anticancer effects of soy foods. In
      part, this is because of the historically low incidence rates of breast and
      prostate cancer in Asia. Of the several putative soybean chemopreventive agents,
      isoflavones have received the most attention. Awareness of this research has led
      increasing numbers of consumers to use soy foods, isoflavone-fortified foods, and
      isoflavone supplements. Therefore, there is a need for guidance regarding
      appropriate isoflavone intake levels. To this end, this article analyzed soy
      protein (as a surrogate for isoflavones) and isoflavone intake of the major soy
      food-consuming countries using individual dietary surveys for the bulk of the
      information. In total, 24 surveys from 4 countries that met the inclusion
      criteria were identified: Japan (n = 11), China (n = 7), Hong Kong (n = 4), and
      Singapore (n = 2). The results indicate that older Japanese adults consume
      approximately 6-11 g of soy protein and 25-50 mg of isoflavones (expressed as
      aglycone equivalents) per day. Intake in Hong Kong and Singapore is lower than in
      Japan, whereas significant regional intake differences exist for China. Evidence
      suggests that < or =10% of the Asian population consumes as much as 25 g of soy
      protein or 100 mg of isoflavones per day. The applicability of these findings for
      making soy intake recommendations for non-Asians is discussed.

PMID- 16965236
TI  - Lycopene intake and prostate cancer risk: effect modification by plasma
      antioxidants and the XRCC1 genotype.
AB  - Lycopene has been associated with reduced prostate cancer risk, although the
      results of epidemiological studies have varied. We hypothesize that an effect of
      lycopene may be modified by XRCC1 genotype and other antioxidants. We used a food
      frequency questionnaire to assess lycopene intake in a case-control study of
      prostate cancer in North Carolina. Plasma alpha-tocopherol and beta-carotene
      levels were measured using high-performance liquid chromatography. XRCC1
      genotypes were detected using polymerase chain reaction-restriction fragment
      length polymorphism. The final dataset included 77 cases and 174 controls with
      complete questionnaires, genotyping, and plasma analyses. Among men with the
      Arg/Arg genotype at codon 399, odds ratios (ORs) for prostate cancer risk
      associated with medium (732-1,529 microg/day) and high (>1,529 microg/day)
      lycopene intake were 0.59 (95% confidence interval = 0.23-1.50) and 0.21 (0.06
      0.71), respectively (P(trend) < 0.01). Similar analyses for persons with Arg/Gln
      or Gln/Gln genotypes produced null results. Above-median (1,048 microg/day)
      lycopene intake combined with above-median levels of alpha-tocopherol and beta
      carotene was associated with an OR of 0.11 (0.02-0.65) among men with the Arg/Arg
      genotype but not those with at least one Gln allele (P(interaction) = 0.01).
      Although limited by small sample size, these findings indicate that the
      association between lycopene and prostate cancer is complex and may be modified
      by other antioxidants and by XRCC1 genotype.

PMID- 16965237
TI  - Saw palmetto supplement use and prostate cancer risk.
AB  - Saw palmetto is an herb used to treat the symptoms of benign prostatic
      hyperplasia. In vitro studies have found that saw palmetto inhibits growth of
      prostatic cancer cells and may induce apoptosis. To evaluate whether saw palmetto
      supplements are associated with a reduced risk of prostate cancer, we conducted a
      prospective cohort study of 35,171 men aged 50-76 yr in western Washington state.
      Subjects completed questionnaires between 2000 and 2002 on frequency of use of
      saw palmetto supplements and saw palmetto-containing multivitamins over the
      previous 10 yr in addition to other information on supplement intake, medical
      history, and demographics. Men were followed through December 2003 (mean of 2.3
      yr of follow-up) via the western Washington Surveillance, Epidemiology, and End
      Results cancer registry, during which time 580 developed prostate cancer. Ten
      percent of the cohort used saw palmetto at least once per week for a year in the
      10 yr before baseline. No association was found between this level of use of saw
      palmetto and risk of prostate cancer development [hazard ratio (HR) = 0.95; 95%
      confidence interval = 0.74-1.23] or with increasing frequency or duration of use.
      In this free-living population, use of commercial saw palmetto, which varies
      widely in dose and constituent ratios, was not associated with prostate cancer
      risk.

PMID- 16965238
TI  - Effects of a low-fat, high-fiber diet and exercise program on breast cancer risk
      factors in vivo and tumor cell growth and apoptosis in vitro.
AB  - The present study investigated the effects of a diet and exercise intervention on
      known breast cancer (BCa) risk factors, including estrogen, obesity, insulin, and
      insulin-like growth factor-I (IGF-I), in overweight/obese, postmenopausal women.
      In addition, using the subjects' pre- and postintervention serum in vitro, serum
      stimulated growth and apoptosis of three estrogen receptor-positive BCa cell
      lines were studied. The women where placed on a low-fat (10-15% kcal), high-fiber
      (30-40 g per 1,000 kcal/day) diet and attended daily exercise classes for 2 wk.
      Serum estradiol was reduced in the women on hormone treatment (HT; n = 28) as
      well as those not on HT (n = 10). Serum insulin and IGF-I were significantly
      reduced in all women, whereas IGF binding protein-1 was increased significantly.
      In vitro growth of the BCa cell lines was reduced by 6.6% for the MCF-7 cells,
      9.9% for the ZR-75-1 cells, and 18.5% for the T-47D cells. Apoptosis was
      increased by 20% in the ZR-75-1 cells, 23% in the MCF-7 cells, and 30% in the T
      47D cells (n = 12). These results show that a very-low-fat, high-fiber diet
      combined with daily exercise results in major reductions in risk factors for BCa
      while subjects remained overweight/obese. These in vivo serum changes slowed the
      growth and induced apoptosis in serum-stimulated BCa cell lines in vitro.

PMID- 16965239
TI  - Vitamin D receptor gene polymorphisms, dietary promotion of insulin resistance,
      and colon and rectal cancer.
AB  - Modifiable risk factors in colorectal cancer etiology and their interactions with
      genetic susceptibility are of particular interest. Functional vitamin D receptor
      (VDR) gene polymorphisms may influence carcinogenesis through modification of
      cell growth, protection from oxidative stress, cell-cell matrix effects, or
      insulin and insulin-like growth factor pathways. We investigated interactions
      between foods (dairy products, red and processed meat, and whole and refined
      grains) and dietary patterns (sucrose-to-fiber ratio and glycemic index)
      associated with insulin resistance with the FokI polymorphism of the VDR gene and
      colon and rectal cancer risk. Data (diet, anthropometrics, and lifestyle) and DNA
      came from case-control studies of colon (1,698 cases and 1,861 controls) and
      rectal cancer (752 cases and 960 controls) in northern California, Utah, and the
      Twin Cities metropolitan area, Minnesota (colon cancer study only). Unconditional
      logistic regression models were adjusted for smoking, race, sex, age, body mass
      index, physical activity, energy intake, dietary fiber, and calcium. The lowest
      colon cancer risk was observed with the Ff/ff FokI genotypes and a low sucrose-to
      fiber ratio. Rectal cancer risk decreased with greater consumption of dairy
      products and increased with red or processed meat consumption and the FF
      genotype. Modifiable dietary risk factors may be differentially important among
      individuals by VDR genotype and may act through the insulin pathway to affect
      colon cancer risk and through fat, calcium, or other means to influence rectal
      cancer risk.

PMID- 16965240
TI  - Women participating in a dietary intervention trial maintain dietary changes
      without much effect on household members.
AB  - This study examined whether subjects who participated in a 12-mo intervention
      would maintain their diets 1 yr after the study ended and whether the diets of
      household members were affected. Premenopausal women, who had at least one first
      degree relative with breast cancer (n = 122), were randomized to one of four
      diets: control, low fat (15% of energy), high fruit and vegetable (FV, nine
      servings per day), and combination low fat, high FV. Study subjects and one
      household member were asked to complete the Block '95 food-frequency
      questionnaire (FFQ) at baseline, 1 yr, and 2 yr. Study subjects also completed 24
      h recalls and 4-day food records at baseline and Year 1. Fat and FV intakes by
      all three assessment methods compared reasonably well except that fat intakes by
      FFQ were somewhat higher. FV intakes by FFQ in the high-FV and combination arms
      increased significantly from 4 servings per day to about 10 servings per day at
      Year 1 and 7 servings per day at Year 2. FV intakes increased much more modestly
      in the low-fat and control arms. Fat intakes in the low-fat and combination arms
      were lower at Year 1 than Year 2, but mean Year 2 fat intakes of 26-28% were
      still significantly lower than those at baseline. In household members, the only
      significant change was a small decrease in energy from fat at Year 1 in the
      household members of subjects who were in the combination arm. These results
      indicate that study subjects were making large dietary changes independently of
      their household members and that fat and FV intakes in study subjects 1 yr after
      intervention stopped were still substantially different from intakes at baseline.

PMID- 16965241
TI  - Safety, tolerance, and metabolism of broccoli sprout glucosinolates and
      isothiocyanates: a clinical phase I study.
AB  - Broccoli sprouts are widely consumed in many parts of the world. There have been
      no reported concerns with respect to their tolerance and safety in humans. A
      formal phase I study of safety, tolerance, and pharmacokinetics appeared
      justified because these sprouts are being used as vehicles for the delivery of
      the glucosinolate glucoraphanin and its cognate isothiocyanate sulforaphane [1
      isothiocyanato-(4R)-(methylsulfinyl)butane] in clinical trials. Such trials have
      been designed to evaluate protective efficacy against development of neoplastic
      and other diseases. A placebo-controlled, double-blind, randomized clinical study
      of sprout extracts containing either glucosinolates (principally glucoraphanin,
      the precursor of sulforaphane) or isothiocyanates (principally sulforaphane) was
      conducted on healthy volunteers who were in-patients on our clinical research
      unit. The subjects were studied in three cohorts, each comprising three treated
      individuals and one placebo recipient. Following a 5-day acclimatization period
      on a crucifer-free diet, the broccoli sprout extracts were administered orally at
      8-h intervals for 7 days (21 doses), and the subjects were monitored during this
      period and for 3 days after the last treatment. Doses were 25 micromol of
      glucosinolate (cohort A), 100 micromol of glucosinolate (cohort B), or 25
      micromol of isothiocyanate (cohort C). The mean cumulative excretion of
      dithiocarbamates as a fraction of dose was very similar in cohorts A and B (17.8
      +/- 8.6% and 19.6 +/- 11.7% of dose, respectively) and very much higher and more
      consistent in cohort C (70.6 +/- 2.0% of dose). Thirty-two types of hematology or
      chemistry tests were done before, during, and after the treatment period.
      Indicators of liver (transaminases) and thyroid [thyroid-stimulating hormone,
      total triiodothyronine (T3), and free thyroxine (T4)] function were examined in
      detail. No significant or consistent subjective or objective abnormal events
      (toxicities) associated with any of the sprout extract ingestions were observed.

PMID- 16965242
TI  - Dietary mineral and trace element intake and squamous cell carcinoma of the
      esophagus in a Chinese population.
AB  - Few studies have been conducted in low-selenium areas of China to assess the
      relationships between dietary intake of selenium and zinc and the risk of
      squamous cell carcinoma of the esophagus (SCCE). We studied dietary mineral and
      trace element intake and risk of SCCE in a population- based, case-control study
      in Taixing, China, in 2000. A total of 218 SCCE patients and 415 population
      healthy controls were interviewed using a standard dietary and health
      questionnaire. The median and quartiles were calculated to represent the average
      level and distribution of selected dietary minerals and trace elements estimated
      by the Chinese Standard Tables of Food Composition. The adjusted odds ratios
      (ORs) comparing the highest with the lowest quartiles were 0.30 (95% confidence
      intervals, CIs = 0.13-0.67) for selenium intake and 0.28 (95% CI = 0.11-0.70) for
      zinc intake with obvious dose-dependent patterns (P values for trend = 0.01). The
      adjusted OR for the combined effect of selenium and zinc intake was 0.53 (95% CI
      = 0.29-0.96) after controlling for potential confounding factors, including age,
      gender, educational level, body mass index, and total energy intake. Our results
      suggested that the potential joint effect of zinc and selenium might contribute
      to SCCE risk. Increased dietary intake of selenium and zinc may decrease the risk
      of SCCE in a low-selenium area of China.

PMID- 16965243
TI  - Antioxidant vitamins and risk of gastric cancer: a case-control study in
      Portugal.
AB  - We quantified the effect of antioxidant vitamins in gastric cancer risk, taking
      into account Helicobacter pylori seropositivity and overall fruit and vegetable
      intake. Incident cases were identified in two large hospitals in Porto, Portugal,
      and controls were randomly sampled among city dwellers. Food intake was assessed
      with a previously validated semiquantitative food-frequency questionnaire. A
      commercially available chromatographic immunoassay was used for the detection of
      immunoglobulin G antibodies. Complete questionnaire information and serum samples
      were available for 233 cases and 311 controls. Compared with subjects in the
      lowest tertile of dietary intake, the odds ratios (ORs) for those in the highest
      were 0.85 (95% confidence interval, CI = 0.45-1.60) for vitamin C, 1.04 (95% CI =
      0.60-1.80) for vitamin E, and 1.33 (95% CI = 0.77-2.30) for provitamin A
      carotenoids after further adjusting for fruit and vegetable consumption. Fruit
      and vegetables remained an independent protective factor (OR = 0.45; 95% CI =
      0.23-0.89) after further adjustment for the intake of antioxidant vitamins. H.
      pylori status had no significant interaction with dietary items. Factors other
      than H. pylori infection and intake of vitamin C and provitamin A carotenoids
      seem to account for the inverse association between fruit and vegetable
      consumption and gastric cancer.

PMID- 16965244
TI  - Evaluation of nutritional and inflammatory status of advanced colorectal cancer
      patients and its correlation with survival.
AB  - The purpose of this study was to evaluate novel inflammatory and nutritional
      prognostic factors in patients with advanced colorectal cancer (ACRC). All ACRC
      patients attending the clinic for palliative treatment were eligible for study.
      Demographics, including performance status (PS), C-reactive protein (CRP),
      albumin (Alb), Glasgow prognostic score (GPS), weight, weight history, body mass
      index (BMI), and nutritional status using the patient-generated subjective global
      assessment (PGSGA), were collected and correlated with survival. At a median
      follow-up of 29.8 mo, with a minimum follow-up of 15.7 mo, the median survival
      was 9.9 mo (0.8-21.8 mo). Fifteen (29%) patients were newly diagnosed (stage IV
      colorectal cancer), and 36 (71%) had received prior chemotherapy. Although the
      median BMI was 27 kg/m2 (range = 17-41 kg/m2), 28 of 50 (56%) were nutritionally
      at risk. In fact, 19 patients (38%) were critically in need of nutrition
      intervention (PGSGA score of > or =9). Thirty-three of 48 patients (69%) had an
      elevated CRP (>10 mg/l with a median of 21.1 mg/L), and 7 patients (15%) had both
      a CRP of >10 mg/l and hypoalbuminemia (< 35 g/l). A significant positive
      correlation was found between PGSGA score and CRP (P = 0.003; r = 0.430). Using
      univariate analysis, significantly worse survival was found for patients with
      poorer PS (P = 0.001), high GPS (P = 0.04), low Alb (P = 0.017), elevated serum
      alkaline phosphatase (SAP; P = 0.018), PGSGA score of > 9 (P = 0.001), and PGSGA
      group B/C (P = 0.02). Using the Cox proportional hazard model for multivariate
      survival analysis, type of treatment (hazard ratio, HR = 1.48; 95% confidence
      interval, CI = 1.11-1.79; P = 0.005), PS (HR = 2.37; 95% CI = 1.11-5.09; P =
      0.026), GPS (HR = 2.27; 95% CI = 1.09-4.73; P = 0.028), and SAP (HR = 0.44; 95%
      CI = 0.18-1.07; P =0.069) remained significant predictors of survival. These
      preliminary data suggest that the type of treatment, PS, GPS, and SAP are
      important predictors of survival in ACRC.

PMID- 16965245
TI  - Mastic oil from Pistacia lentiscus var. chia inhibits growth and survival of
      human K562 leukemia cells and attenuates angiogenesis.
AB  - Mastic oil from Pistacia lentiscus var. chia, a natural plant extract
      traditionally used as a food additive, has been extensively studied for its
      antimicrobial activity attributed to the combination of its bioactive components.
      One of them, perillyl alcohol (POH), displays tumor chemopreventive,
      chemotherapeutic, and antiangiogenic properties. We investigated whether mastic
      oil would also suppress tumor cell growth and angiogenesis. We observed that
      mastic oil concentration and time dependently exerted an antiproliferative and
      proapoptotic effect on K562 human leukemia cells and inhibited the release of
      vascular endothelial growth factor (VEGF) from K562 and B16 mouse melanoma cells.
      Moreover, mastic oil caused a concentration-dependent inhibition of endothelial
      cell (EC) proliferation without affecting cell survival and a significant
      decrease of microvessel formation both in vitro and in vivo. Investigation of
      underlying mechanism(s) demonstrated that mastic oil reduced 1) in K562 cells the
      activation of extracellular signal-regulated kinases 1/2 (Erk1/2) known to
      control leukemia cell proliferation, survival, and VEGF secretion and 2) in EC
      the activation of RhoA, an essential regulator of neovessel organization.
      Overall, our results underscore that mastic oil, through its multiple effects on
      malignant cells and ECs, may be a useful natural dietary supplement for cancer
      prevention.

PMID- 16965246
TI  - Diallyl trisulfide inhibits angiogenic features of human umbilical vein
      endothelial cells by causing Akt inactivation and down-regulation of VEGF and
      VEGF-R2.
AB  - We have shown recently that diallyl trisulfide (DATS), a cancer-chemopreventive
      constituent of garlic, inactivates Akt to trigger mitochondrial translocation of
      proapoptotic protein BAD in human prostate cancer cells. Because Akt activation
      is implicated in the promotion of endothelial cell survival and angiogenesis, we
      hypothesized that DATS may inhibit angiogenesis. In the present study, we tested
      this hypothesis using human umbilical vein endothelial cells (HUVECs) as a model.
      Survival of HUVECs was reduced significantly in the presence of DATS in a
      concentration-dependent manner, with an IC50 of approximately 4 microM. The DATS
      mediated suppression of HUVEC survival was associated with apoptosis induction
      characterized by accumulation of subdiploid cells, cytoplasmic histone-associated
      DNA fragmentation, and cleavage of caspase-3 and poly-(ADP-ribose)-polymerase.
      The DATS-induced DNA fragmentation was significantly attenuated in the presence
      of pan-caspase inhibitor zVAD-fmk and specific inhibitors of caspase-9 (zLEHD
      fmk) and caspase-8 (zIETD-fmk). DATS treatment inhibited the formation of
      capillary-like tube structure and migration by HUVECs in association with
      suppression of vascular endothelial growth factor (VEGF) secretion and VEGF
      receptor-2 protein level and inactivation of Akt kinase. DATS treatment also
      caused activation of extracellular signal-regulated kinase 1/2 (ERK1/2) but not c
      Jun NH2-terminal kinase (JNK) or p38 mitogen-activated protein kinase
      (p38MAPK).DATS-mediatedapoptosis induction and inhibition of HUVEC tube formation
      was partially but statistically significantly attenuated by pharmacologic
      inhibition of ERK1/2 but not JNK or p38MAPK. The present study demonstrates, for
      the first time, that DATS has the ability to inhibit angiogenic features of human
      endothelial cells.

PMID- 16965248
TI  - Seventy-five (count 'em-75!) issues of Health Communication: an analysis of
      emerging themes.

PMID- 16965249
TI  - Emerging trends and future directions in patient communication skills training.
AB  - Despite several reviews of research on the effects of patient communication
      skills interventions, relatively few new studies on the topic have been published
      recently. The purpose of this article is to identify areas of needed research
      into patient communication skills training, with the intent of stimulating
      further investigation. Several topics are discussed, including longitudinal
      research, issues for studying underserved populations, the role of patients'
      preference for involvement with their health care, and the assessment of the
      effects of patient communication skills training on health outcomes.

PMID- 16965250
TI  - Health and the information nonseeker: a profile.
AB  - Despite increased information-seeking by the public, a significant percentage of
      those diagnosed with a serious disease such as cancer report that they do not
      seek or receive health information beyond that given by health care providers.
      This study attempts to profile these nonseekers and study possible determinants
      of nonseeking behaviors. Data come from the 2003 Health Information National
      Trends Survey, a national survey of American adults conducted by the National
      Cancer Institute ( N = 6,133; Nelson et al., 2004). Individuals were categorized
      as nonseekers or seekers and then further classified based on cancer history to
      yield 4 groups: nonseeker patients, the nonseeker public, seeker patients, and
      the seeker public. Compared to other groups, nonseeker patients came from the
      lowest income and education groups, and scored lower on attention to health in
      the media and trust in mass media health information. Nonseekers also scored
      lower on preventative health behaviors.

PMID- 16965251
TI  - Order out of chaos: the self-organization of communication following the anthrax
      attacks.
AB  - This article describes 5 communication challenges faced by the author as she
      managed the communication response by the Centers for Disease Control and
      Prevention to the anthrax attacks of 2001: communicating uncertainty, selecting
      credible spokespersons, collaborating with other organizations, satisfying a
      competitive 24/7 media, and speed. The lessons learned in responding to these
      challenges led to profound changes in the way communication was organized in the
      agency. These changes are described within the framework of chaos theory.

PMID- 16965252
TI  - Specification and misspecification of theoretical foundations and logic models
      for health communication campaigns.
AB  - While increasingly widespread use of behavior change theory is an advance for
      communication campaigns and their evaluation, such theories provide a necessary
      but not sufficient condition for theory-based communication interventions. Such
      interventions and their evaluations need to incorporate theoretical thinking
      about plausible mechanisms of message effect on health-related attitudes and
      behavior. Otherwise, strategic errors in message design and dissemination, and
      misspecified campaign logic models, insensitive to campaign effects, are likely
      to result. Implications of the elaboration likelihood model, attitude
      accessibility, attitude to the ad theory, exemplification, and framing are
      explored, and implications for campaign strategy and evaluation designs are
      briefly discussed. Initial propositions are advanced regarding a theory of
      campaign affect generalization derived from attitude to ad theory, and regarding
      a theory of reframing targeted health behaviors in those difficult contexts in
      which intended audiences are resistant to the advocated behavior or message.

PMID- 16965253
TI  - On the use of structural equation modeling in health communication research.
AB  - Structural equation modeling (SEM) is a multivariate technique suited for testing
      proposed relations between variables. In this article, the authors discuss the
      potential for SEM as a tool to advance health communication research both
      statistically and conceptually. Specifically, the authors discuss the advantages
      that latent variable modeling in SEM affords researchers by extracting
      measurement error. In addition, they argue that SEM is useful in understanding
      communication as a complex set of relations between variables. Moreover, the
      authors articulate the possibility for examining communication as an agent,
      mediator, and an outcome. Finally, they review the application of SEM to
      recursive models, interactions, and confirmatory factor analysis.

PMID- 16965254
TI  - In pursuit of cumulative knowledge in health communication: the role of meta
      analysis.
AB  - A major goal in health communication and related disciplines is the building of
      cumulative knowledge across numerous lines of inquiry. Traditionally, attempts to
      synthesize research and build knowledge have been achieved through narrative or
      integrative research reviews. However, the advent of meta-analysis in the late
      1970s gave researchers a more sophisticated approach to synthesizing quantitative
      research literatures. This article (a) provides an overview of the meta-analytic
      approach, (b) discusses the historical context of meta-analysis, (c) examines the
      role that meta-analysis has played in the synthesis of health communication
      research, and (d) suggests future applications of the technique within health
      communication. It appears that meta-analysis has only recently been applied to
      the health communication field in a substantive way, and that its potential for
      moving the field forward has thus only begun to be realized.

PMID- 16965255
TI  - Understanding medical interpreters: reconceptualizing bilingual health
      communication.
AB  - This article provides a new approach in conceptualizing bilingual health
      communication, emphasizing the differences between types of medical interpreters
      as well as the interrelationships among all participants in bilingual health
      communication. Confronted by the conflicting results of interpreting services in
      medical settings, the author used past research to explain why medical
      interpreters should be categorized into different categories (i.e., chance
      interpreters, untrained interpreters, bilingual health care providers, on-site
      interpreters, and telephone interpreters) so that their characteristics and
      interpreting styles can be better observed and understood. In addition, by
      recognizing that interpreter-mediated communications in health settings are
      dynamic situations and that all participants can influence the outcomes of the
      communication, researchers can start to investigate the interrelationships among
      all the participants and, thus, develop different strategies that will improve
      the quality of bilingual health communication.

PMID- 16965256
TI  - Discourse analytic study of counseling sessions in stroke physiotherapy.
AB  - Studies on the interaction between physiotherapists and patients during treatment
      sessions have found low levels of communicative participation by patients and
      lack of direct influence by patients on the content of their treatment. This
      article reports the results of 7 counseling sessions in which physiotherapists
      and patients with stroke and their caregivers discussed the patients' postural
      control and balance, which had been tested and videotaped at different stages of
      the rehabilitation process. The physiotherapists' discourses relating to the
      videotaped test performances were either brief comments on the patient's
      performance or critical appraisals with references to difficulties encountered
      during performance. Performances of the easier tasks were treated by the
      physiotherapists with rhetorical questions. The second type of discourse
      consisted of the physiotherapists directing the patients' attention to their
      problems, and of the patients' and caregivers' initiatives leading to
      conversation about the patients' problems. The patients understood the
      significance of the test performance for their life at home in varying ways. The
      results of this study showed that successful counseling calls for
      physiotherapists to develop dialogic communication skills to help patients in
      coconstructing their home exercise together with their social network.

PMID- 16965257
TI  - The ten commandments of reviewing: the promise of a kinder, gentler discipline!

PMID- 16965259
TI  - Bibliography.

PMID- 16965261
TI  - C-terminal region regulates the functional expression of human noradrenaline
      transporter splice variants.
AB  - The NET [noradrenaline (norepinephrine) transporter], an Na+/Cl--dependent
      neurotransmitter transporter, has several isoforms produced by alternative
      splicing in the C-terminal region, each differing in expression and function. We
      characterized the two major isoforms of human NET, hNET1, which has seven C
      terminal amino acids encoded by exon 15, and hNET2, which has 18 amino acids
      encoded by exon 16, by site-directed mutagenesis in combination with NE
      (noradrenaline) uptake assays and cell surface biotinylation. Mutants lacking one
      third or more of the 24 amino acids encoded by exon 14 exhibited neither cell
      surface expression nor NE uptake activity, with the exception of the mutant
      lacking the last eight amino acids of hNET2, whose expression and uptake
      resembled that of the WT (wild-type). A triple alanine replacement of a candidate
      motif (ENE) in this region mimicked the influences of the truncation. Deletion of
      either the last three or another four amino acids of the C-terminus encoded by
      exon 15 in hNET1 reduced the cell surface expression and NE uptake, whereas
      deletion of all seven residues reduced the transport activity but did not affect
      the cell surface expression. Replacement of RRR, an endoplasmic reticulum
      retention motif, by alanine residues in the C-terminus of hNET2 resulted in a
      similar expression and function compared with the WT, while partly recovering the
      effects of the mutation of ENE. These findings suggest that in addition to the
      function of the C-terminus, the common proximal region encoded by exon 14
      regulates the functional expression of splice variants, such as hNET1 and hNET2.

PMID- 16965262
TI  - Involvement of the ubiquitous Oct-1 transcription factor in hormonal induction of
      beta-casein gene expression.
AB  - Transcription of the milk protein beta-casein gene is induced by the lactogenic
      hormones Prl (prolactin) and glucocorticoids. Multiple transcription factors
      involved in this induction have been identified, including the STAT5 (signal
      transducer and activator of transcription 5) and the GR (glucocorticoid
      receptor). Our previous studies have identified a binding site for the ubiquitous
      Oct-1 (octamer-binding transcription factor 1) protein in the lactogenic hormonal
      regulatory region of the mouse beta-casein promoter. In the present study, we
      report that Oct-1 is indeed expressed and binds to the beta-casein promoter in
      mammary epithelial cells. Oct-1 activates hormonally induced beta-casein promoter
      activity in a dose-dependent manner. Hormonal induction of promoter activity was
      decreased not only by mutating the Oct-1-binding site from ATTAGCAT to GCTAGCAT,
      which abolishes Oct-1 binding (50% decrease, P<0.01), but also by changing the
      site to the consensus Oct-1-binding motif ATTTGCAT (40% decrease, P<0.01).
      Reversing the Oct-1-binding site reduced hormonal induction by 70% (P<0.01),
      showing that orientation of Oct-1 binding is also critical in hormonal action. In
      transient transfection experiments, Oct-1 collaboratively transactivated the beta
      casein gene promoter with STAT5 and/or GR in the presence of Prl receptor in
      cells treated with the lactogenic hormones. The C-terminus of Oct-1 was not
      essential to its function. The results of the present study provide biochemical
      evidence that the ubiquitous Oct-1 transcription factor may be involved in
      hormonally regulated, tissue-specific beta-casein gene expression.

PMID- 16965263
TI  - Prolactin stimulates prostate cell proliferation by increasing endoplasmic
      reticulum content due to SERCA 2b over-expression.
AB  - Prolactin (PRL) has been shown to be involved in the differentiation and
      proliferation of numerous tissues, including the prostate gland. Moreover,
      variations in [Ca2+]ER (calcium concentration within the endoplasmic reticulum)
      may play a role in cell growth. However, few studies have focused on the
      regulation of calcium homoeostasis by prolactin. The present study evaluates the
      regulation of calcium pools as well as the possible role of [Ca2+]ER variations
      as a signal for growth modulation by PRL. We show that PRL stimulates the
      proliferation of normal SV40 immortalized epithelial prostate (PNT1A) cells with
      a maximum effect at a dose of 100 ng/ml. We also show that 100 ng/ml PRL
      increases the [Ca2+]ER when measured either by indirect quantification with Fura
      2AM after application of 1 mM thapsigargin or by direct quantification with Mag
      Fura-2AM within the endoplas-mic reticulum. Western blot analysis shows that the
      SERCA 2b (sarcoendoplasmic calcium ATPase 2b) is over-expressed in PNT1A cells
      treated with 100 ng/ml PRL for 24 h. A small inter-fering RNA SERCA 2a/b, used to
      down-regulate endogenous SERCA 2b expression, reduced both PNT1A cell
      proliferation and [Ca2+]ER. We thus identify [Ca2+]ER and SERCA 2b as
      protagonists in PRL-induced proliferation.

PMID- 16965264
TI  - Molecular and functional characterization of microsomal UDP-glucuronic acid
      uptake by members of the nucleotide sugar transporter (NST) family.
AB  - Transport of the co-substrate UDPGA (UDP-glucuronic acid) into the lumen of the
      endoplasmic reticulum is an essential step in glucuronidation reactions due to
      the intraluminal location of the catalytic site of the enzyme UGT (UDP
      glucuronosyltransferase). In the present study, we have characterized the
      function of several NSTs (nucleotide sugar transporters) and UGTs as potential
      carriers of UDPGA for glucuronidation reactions. UDPGlcNAc (UDP-N
      acetylglucosamine)-dependent UDPGA uptake was found both in rat liver microsomes
      and in microsomes prepared from the rat hepatoma cell line H4IIE. The latency of
      UGT activity in microsomes derived from rat liver and V79 cells expressing UGT1A6
      correlated well with mannose-6-phosphatase latency, confirming the UGT in the
      recombinant cells retained a physiology similar to rat liver microsomes. In the
      present study, four cDNAs coding for NSTs were obtained; two were previously
      reported (UGTrel1 and UGTrel7) and two newly identified (huYEA4 and huYEA4S).
      Localization of NSTs within the human genome sequence revealed that huYEA4S is an
      alternatively spliced form of huYEA4. All the cloned NSTs were stably expressed
      in V79 (Chinese hamster fibroblast) cells, and were able to transport UDPGA after
      preloading of isolated microsomal vesicles with UDPGlcNAc. The highest uptake was
      seen with UGTrel7, which displayed a V(max) approx. 1% of rat liver microsomes.
      Treatment of H4IIE cells with beta-naphthoflavone induced UGT protein expression
      but did not affect the rate of UDPGA uptake. Furthermore, microsomes from UGT1
      deficient Gunn rat liver showed UDPGA uptake similar to those from control rats.
      These data show that NSTs can act as UDPGA transporters for glucuronidation
      reactions, and indicate that UGTs of the 1A family do not function as UDPGA
      carriers in microsomes. The cell line H4IIE is a useful model for the study of
      UDPGA transporters for glucuronidation reactions.

PMID- 16965265
TI  - Design and characterization of a platelet-targeted plasminogen activator with
      enhanced thrombolytic and antithrombotic potency.
AB  - To obtain a thrombus-targeted plasminogen activator with high affinity for
      activated platelets and enhanced thrombolytic and antithrombotic potency, we
      engineered a sequence encoding RGDS (Arg-Gly-Asp-Ser) peptide into the loop
      between domains II and III of the sequence-deleted mutant of annexin B1 and then
      constructed a chimaeric plasminogen activator gene mAnxB1-RGDS-ScuPA by fusing
      ScuPA32k [low-molecular-mass single-chain urokinase (32 kDa)] with the N
      terminus. The chimaeric protein was expressed in inclusion bodies in Escherichia
      coli at 25% of the total cellular protein content. Ion-exchange and gel
      filtration chromatographies were applied to purify the chimaeric protein,
      achieving purity greater than 98%. We demonstrated that this chimaera can be
      expressed and purified in an active form; in vitro testing indicated that the
      chimaera fully retained the thrombolytic activity, platelet membrane-binding
      activity and anti-platelet aggregation activity of the parent molecules. The
      plasma clearance of the chimaera was similar to that of urokinase and ScuPA32k.
      In vivo experiments in a canine system indicated that animals administered the
      chimaera presented a decreased time to reperfusion, higher reperfusion ratio and
      less bleeding effects than treatment with urokinase. These results show that the
      chimaera is a platelet-targeted plasminogen activator with enhanced thrombolytic
      and antithrombotic potency that may have advantages over currently available
      thrombolytic agents.

PMID- 16965266
TI  - Editorial: vigour, vitiligo and the RPE.

PMID- 16965268
TI  - Bioimmunotherapy for melanoma using fully human antibodies targeting MCAM/MUC18
      and IL-8.
AB  - Metastatic melanoma is associated with high rate of patients' mortality and
      represents a great challenge for cancer therapies because of its notorious
      resistance to chemotherapeutic drugs. Considerable efforts have been made over
      the last 2 decades in pursuit of new treatment modalities and identification of
      molecular events associated with melanoma progression and development of
      metastases. The acquisition of the metastatic phenotype is associated with
      overexpression of the adhesion molecule MCAM/MUC18 and the angiogenic factor IL
      8. In this review, we summarize our current knowledge on MCAM/MUC18 and IL-8,
      their transcriptional regulation, and their role in melanoma growth, angiogenesis
      and metastasis. Further, we report on the development of new fully human
      antibodies, anti-MCAM/MUC18 (ABX-MA1) and anti-IL-8 (ABX-IL8), and their effects
      on tumor growth and metastasis in animal models. Collectively, our studies
      suggest that ABX-MA1 and ABX-IL8 could serve as new modalities for the treatment
      of melanoma either alone, or in combination with conventional chemotherapy or
      other antitumor agents.

PMID- 16965267
TI  - The other pigment cell: specification and development of the pigmented epithelium
      of the vertebrate eye.
AB  - Vertebrate retinal pigment epithelium (RPE) cells are derived from the
      multipotent optic neuroepithelium, develop in close proximity to the retina, and
      are indispensible for eye organogenesis and vision. Recent advances in our
      understanding of RPE development provide evidence for how critical signaling
      factors operating in dorso-ventral and distal-proximal gradients interact with
      key transcription factors to specify three distinct domains in the budding optic
      neuroepithelium: the distal future retina, the proximal future optic stalk/optic
      nerve, and the dorsal future RPE. Concomitantly with domain specification, the
      eye primordium progresses from a vesicle to a cup, RPE pigmentation extends
      towards the ventral side, and the future ciliary body and iris form from the
      margin zone between RPE and retina. While much has been learned about the
      molecular networks controlling RPE cell specification, key questions concerning
      the cell proliferative parameters in RPE and the subsequent morphogenetic events
      still need to be addressed in greater detail.

PMID- 16965269
TI  - A review and a new hypothesis for non-immunological pathogenetic mechanisms in
      vitiligo.
AB  - Vitiligo is an acquired depigmenting disorder characterized by the loss of
      functioning epidermal melanocytes because of multifactorial and overlapping
      pathogenetic mechanisms. Besides the immunological approach, the study of the
      metabolic deregulations leading to toxic damage of the melanocytes appears to be
      more and more relevant. It was only last year that the first in vitro evidence
      supporting the link and the temporal sequence between the immune response and the
      cellular oxidative stress was provided, suggesting that the intrinsic damage of
      the melanocytes is primitive. What can be the guide line of the multiple altered
      metabolisms? A compromised membrane could render the cell sensitive to the
      external and internal agents differently, usually ineffective on the cell
      activity and survival. The primitive altered arrangement of the lipids may affect
      the transmembrane housing of proteins with enzymatic or receptorial activities,
      also conferring on them antigenic properties.

PMID- 16965270
TI  - Rab7 and Rab27a control two motor protein activities involved in melanosomal
      transport.
AB  - Melanosomes are lysosome-related organelles that synthesize, store and transport
      melanin. In epidermal melanocytes, melanosomes mature and are transferred to
      surrounding keratinocytes, which is essential for skin and coat colour. Mouse
      coat colour mutants reveal a critical role for the small GTPase Rab27a, which
      recruits myosin Va through its effector protein melanophilin/Slac2a. Here we have
      studied how two different Rab GTPases control two motor proteins during
      subsequent phases in transport of melanosomes. We show that the small GTPase Rab7
      mainly associates with early and intermediate stage melanosomes and Rab27a to
      intermediate and mature melanosomes. Rab27a is found in an active state on mature
      melanosomes in the tips of the dendrites. The Rab7-Rab7-interacting lysosomal
      protein-dynein pathway only controls early and intermediate stage melanosomes
      because the mature melanosomes lack Rab7 and associate with the actin network
      through Rab27a recruited MyoVa. Thus two Rab proteins regulate two different
      motor proteins, thereby controlling complementary phases in melanosome
      biogenesis: Rab7 controls microtubule-mediated transport of early and Rab27a the
      subsequent actin-dependent transport of mature melanosomes.

PMID- 16965271
TI  - Increased expression of integrins and decreased apoptosis correlate with
      increased melanocyte retention in cultured skin substitutes.
AB  - Losses of human melanocytes (HM) in transplantation of cultured skin substitutes
      (CSS) may result from poor cellular attachments. To test this hypothesis, HM
      integrin expression was measured in four culture media: (a) melanocyte growth
      medium (MGM), an HM proliferation medium; (b) UCMC 160, a CSS maturation medium;
      (c) mMGM, modified MGM with 1.8 mM calcium; and (d) modified UCMC 160 with HM
      supplements (mUCMC 160). HM grew well in all media except UCMC 160. Increased
      expression of beta1, beta4, alpha3beta1 and alpha5 integrins on HM cultured in
      MGM and mMGM versus UCMC 160 was found by flow cytometry. Annexin V
      allophycocyanin (APC) labeled HM in apoptosis and increased significantly in UCMC
      160 (31.1%) compared with MGM (11.9%) or mMGM (13.9%). CSS were incubated in UCMC
      160, mMGM or mUCMC 160 media, and grafted to athymic mice. In the mMGM group,
      grafts were darker as measured with a chromameter through 6 weeks and the average
      number of basal HM per field was greater at 12 weeks post-grafting. Increased
      graft loss was observed in the mMGM group which corresponded with the poor
      epidermal morphology in vitro. Although HM retention improved in vivo using mMGM
      to culture the CSS, the stability of the epidermis decreased. These results
      indicate that expression of integrins on HM in vitro correlates with HM retention
      in CSS and short-term survival after transplantation, but that long-term survival
      depends also on stable epithelium.

PMID- 16965272
TI  - In vivo and in vitro evidence of dermal fibroblasts influence on human epidermal
      pigmentation.
AB  - Using chimeric human epidermal reconstructs, we previously demonstrated that
      epidermal pigmentation is dependent upon the phototype of melanocytes. We report
      here several lines of experimental evidence for dermal modulation of human
      epidermal pigmentation. First, phototype II-III epidermal reconstructs grafted on
      the back of immunotolerant Swiss nu/nu mice developed a patchy pigmentation
      dependent on the presence of colonizing human or mouse fibroblasts. Similarly,
      human white Caucasoid split-thickness skin xenografted on the same mouse strain
      became black within 3 months and histochemistry revealed a phototype VI pattern
      of melanin distribution. In vitro, human fibroblasts colonizing human dead de
      epidermized dermis (DDD) induced a decrease in epidermal pigmentation whereas
      mouse (Swiss nu/nu) fibroblasts increased epidermal pigmentation. Conditioned
      medium from mice (Swiss nu/nu) fibroblasts also increased pigmentation whereas
      conditioned medium from human fibroblasts had no significant effect. Lastly,
      epidermal reconstructs made with normal or vitiligo keratinocytes and/or normal
      or vitiligo melanocytes from the same donor grown on DDD originating from several
      donors of the same clinical phototype did not pigment similarly and no specific
      dermal influence was noted for vitiligo. Thus, fibroblast secretion and acellular
      dermal connective tissue itself significantly influence melanocyte proliferation
      and melanin distribution/degradation. Our study suggests that murine fibroblasts
      are more potent than human fibroblasts in secreting soluble factors which can act
      directly on pigmentation, such as SCF, or activate keratinocytes to produce
      basement membrane proteins or melanogenic factors.

PMID- 16965273
TI  - Dopaquinone redox exchange with dihydroxyindole and dihydroxyindole carboxylic
      acid.
AB  - A pulse radiolytic investigation has been conducted to establish whether a redox
      reaction takes place between dopaquinone and 5,6-dihydroxyindole (DHI) and its 2
      carboxylic acid (DHICA) and to measure the rate constants of the interactions. To
      obviate possible confounding reactions, such as nucleophilic addition, the method
      employed to generate dopaquinone used the dibromide radical anion acting on dopa
      to form the semiquinone which rapidly disproportionates to dopaquinone. In the
      presence of DHI the corresponding indole-5,6-quinone (and/or tautomers) was also
      formed directly but, by judicious selection of suitable relative concentrations
      of initial reactants, we were able to detect the formation of additional
      indolequinone from the redox exchange reaction of DHI with dopaquinone which
      exhibited a linear dependency on the concentration of DHI. Computer simulation of
      the experimental time profiles of the absorption changes showed that, under the
      conditions chosen, redox exchange does proceed but not quite to completion, a
      forward rate constant of 1.4 x 10(6)/M/s being obtained. This is in the same
      range as the rate constants previously established for reactions of dopaquinone
      with cyclodopa and cysteinyldopa. In similar experiments carried out with DHICA,
      the reaction more obviously does not go to completion and is much slower, k
      (forward) =1.6 x 10(5)/M/s. We conclude that, in the eumelanogenic pathway, DHI
      oxidation may take place by redox exchange with dopaquinone, although such a
      reaction is likely to be less efficient for DHICA.

PMID- 16965274
TI  - Oculocutaneous albinism type 4: six novel mutations in the membrane-associated
      transporter protein gene and their phenotypes.
AB  - Oculocutaneous albinism type 4 (OCA4) is an autosomal recessive hypopigmentary
      disorder caused by mutations in the Membrane-Associated Transporter Protein gene
      (SLC45A2). The SLC45A2 protein is a 530-amino-acid polypeptide that contains 12
      putative transmembrane domains, and appears to be a transporter that mediates
      melanin synthesis. Eighteen pathological mutations have been reported so far. In
      this study, six novel mutations, p.Y49C (c.146A > G), p.G89R (c.265G > A),
      p.C229Y (c.686G > A), p.T437A (c.1309A > G), p.T440A (c.1318A > G) and p.G473D
      (c.1418G > A) were found in eight Japanese patients with various clinical
      phenotypes. The phenotypes of OCA4 were as various as the other types of OCA and
      probably depended on the mutation sites in the SLC45A2 gene.

PMID- 16965275
TI  - The slaty mutation affects the morphology and maturation of melanosomes in the
      mouse melanocytes.
AB  - The slaty (Dct(slt)) mutation is known to reduce the activity of dopachrome
      tautomerase in melanocytes and to reduce the melanin content in skin, hairs and
      eyes. Although the melanosomes in slaty melanocytes are reported to be
      eumelanosome-like, detailed melanosome biogenesis is not well studied. To address
      this point, melanosomes in neonatal epidermal melanocytes from wild-type
      (Dct+/Dct+) mice at the slaty locus as well as its congenic mouse mutant
      (Dct(slt)/Dct(slt)) in serum-free primary culture were observed under the
      electron microscope. Wild-type melanocytes possessed exclusively elliptical
      melanosomes with internal longitudinal structures, whereas in mutant melanocytes,
      numerous spherical melanosomes with globular depositions of pigment and
      elliptical melanosomes as well as mixed type of the two melanosomes were
      observed. Mature stage IV melanosomes were greatly decreased in mutant
      melanocytes, whereas immature stage III melanosomes were more numerous than in
      wild-type melanocytes. These results suggest that the slaty mutation affects the
      morphology and maturation of melanosomes in mouse melanocytes.

PMID- 16965276
TI  - Evaluation of melanin-related metabolites as markers of solar ultraviolet-B
      radiation.
AB  - Ultraviolet-B (UVB) radiation due sunlight can result in sunburns and/or suntans.
      Sunburn occurs only several hours after solar UVB radiation, while a suntan
      requires several days to several weeks to develop. In the present study, we
      measured serum and urine levels of melanin-related metabolites, 5-S-cysteinyldopa
      (5-S-CD) and 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C), in nine
      subjects exposed to normal sunlight over the course of 12 months. We collected
      samples in the middle of each month and examined the variation of the markers,
      the correlation between them, and their correlation with solar UVB radiation.
      Those markers exhibited a seasonal variation with lower values in the winter and
      higher values in the summer. Levels of 5-S-CD and 6H5MI2C in the serum showed 48%
      and 54% increases in the summer compared with those in the winter, respectively.
      Comparison of 5-S-CD in the serum and urine showed the highest correlation (r2 =
      0.344), followed by the pair of 5-S-CD and 6H5MI2C in the serum. Levels of 5-S-CD
      in the serum showed the highest correlation (r2 = 0.729) with the mean solar UVB
      radiation during the first 10 d of the month, while 6H5MI2C in the serum was
      highly correlated (r2 = 0.483) with solar UVB radiation during the previous
      month. Levels of 5-S-CD and 6H5MI2C in the serum appear to reflect the degrees of
      skin injury and pigmentation in the skin, respectively.

PMID- 16965277
TI  - Melanin structure and the potential functions of uveal melanosomes.

PMID- 16965283
TI  - Immune modulation by helminth infections.

PMID- 16965284
TI  - Immune modulation by helminthic infections: worms and viral infections.
AB  - Helminthic infections occur worldwide, especially in developing countries. About
      one-quarter of the world's population, 1.5 billion, are infected with one or more
      of the major soil-transmitted helminths, including hookworms, ascarids, and
      whipworms. Schistosomes infect more than 200 million people worldwide with 600
      million at risk in 74 countries. The interaction between helminths and the host's
      immune system provokes particular immunomodulatory and immunoregulatory
      mechanisms that ensure their survival in the host for years. However, these
      changes might impair the immunological response to bystander bacterial, viral,
      and protozoal pathogens and to vaccination. Modulation of the immune system by
      infection with helminthic parasites is proposed to reduce the levels of allergic
      responses and to protect against inflammatory bowel disease. In this review, we
      summarize the immunological milieu associated with helminthic infections and its
      impact on viral infections, mainly hepatitis B virus, hepatitis C virus, and
      human immunodeficiency virus in humans and experimental animals.

PMID- 16965285
TI  - Co-infection of helminths and malaria: modulation of the immune responses to
      malaria.
AB  - Chronic helminth infections induce strong type 2 and regulatory immune responses
      and are known to influence immune activity to other antigens such as allergens
      and vaccines. Since malaria and helminth infections often coincide geographically
      in the same tropical regions, the question arises whether helminth infections
      modulate the immune responses towards the malaria parasite and affect its course
      of disease. Here, we will review studies on co-infections in both animal models
      and in human populations, and discuss the changes in the immune system seen.
      Furthermore, the implications of helminth infection for the efficacy of malaria
      vaccines will be discussed.

PMID- 16965286
TI  - Helminthes could influence the outcome of vaccines against TB in the tropics.
AB  - Helminthes, infections widespread in the tropics, are known to elicit a wide
      range of immunomodulation characterized by dominant Th2 type immune responses,
      chronic immune activation as well as up-regulated regulatory T cell activity.
      Such a wide range of immunomodulation caused by helminthes may have an impact on
      the host's ability to cope with subsequent infections and/or may affect the
      efficacy of vaccination. Indeed studies conducted in humans living in helminth
      endemic areas and in animal models showed that helminth infection makes the host
      more permissive to mycobacterial infections and less able to benefit from
      vaccination. These observations have fundamental practical consequences if
      confirmed by large and appropriately controlled clinical studies. Eradication of
      worms could offer an affordable, simple and novel means to reduce the burden of
      the tuberculosis problem that at the moment seems to be getting out of control in
      sub-Saharan Africa. This information would also be of great relevance in the
      design of vaccines against diseases of major public health importance, including
      malaria and HIV/AIDS.

PMID- 16965288
TI  - Worms and allergy.
AB  - Worms and asthma are associated with a type 2 immune response, but evidence has
      accumulated that helminth infection is negatively associated with atopy,
      prevalence of allergic diseases and severity of asthma. One important difference
      between these polarized type 2 responses is that in allergy modulation of the
      immunological response is not appropriate, whereas in infection with helminths,
      several host mechanisms down-regulate the host immune response. As a result,
      patients infected with worms have a decrease in both type 1 and type 2 responses.
      The main mechanism involved in this down-modulation is increased production of IL
      10, but expansion of regulatory T cells and NKT cells may also participate.
      Regarding the interaction between worms and allergy, a few variables need to be
      taken in account: phase (acute or chronic) of helminth infection, parasite load
      and species of helminth. In animals and humans, acute helminth infection may
      increase manifestations of allergy, whereas chronic infection with parasites
      decreases atopy. The modulation of the immune response by helminths is dependent
      on having an adequate parasite load. Moreover, although several helminth species
      have been shown to modulate immune responses, most in vitro and in vivo studies
      have focused on the importance of Schistosoma mansoni in down-modulating allergic
      reactions.

PMID- 16965287
TI  - Parasitic worms and inflammatory diseases.
AB  - The debate on whether infection precipitates or prevents autoimmunity remains a
      contentious one. Recently the suggestion that some unknown microbe can be at the
      origin of some chronic inflammatory diseases has been countered by accumulating
      evidence that decreasing infection rates might have an important role to play in
      the rising prevalence of autoimmune disorders. The 'Hygiene Hypothesis' was
      initially postulated to explain the inverse correlation between the incidence of
      infections and the rise of allergic diseases, particularly in the developed
      world. Latterly, the Hygiene Hypothesis has been extended to also incorporate
      autoimmune diseases in general. Amongst the various infectious agents, a
      particular emphasis has been put on the interaction between parasitic worms and
      humans. Worm parasites have co-evolved with the mammalian immune system for many
      millions of years and during this time, they have developed extremely effective
      strategies to modulate and evade host defences and so maintain their evolutionary
      fitness. It is therefore reasonable to conclude that the human immune system has
      been shaped by its relationship with parasitic worms and this may be a necessary
      requirement for maintaining our immunological health. Fully understanding this
      relationship may lead to novel and effective treatments for a host of deleterious
      inflammatory reactions.

PMID- 16965289
TI  - Molecular basis of worm-induced immunomodulation.
AB  - Long-term infection with parasitic worms is generally associated with an
      immunological phenotype that is Th2-like and anti-inflammatory. This phenotype is
      probably an unintentional consequence of molecular characteristics of worms (as
      free-living worms also express polarising molecules) in combination with
      deliberate attempts by the parasites, via molecular secretions, to modulate the
      phenotype. This review is concerned with the identity of immunomodulatory worm
      products, the receptors that they interact with and the signal transduction
      pathways that they activate. It hopes to indicate how knowledge of these factors
      can explain the changes in gene expression that result in the characteristic worm
      induced immunological phenotype.

PMID- 16965290
TI  - Hypothalamic expression of human growth hormone induces post-pubertal
      hypergonadotrophism in male transgenic growth retarded rats.
AB  - Growth hormone (GH) is known to regulate peripheral components of the hypothalamo
      pituitary gonadal (HPG) axis, but it remains unclear whether GH exerts a
      significant influence on the activity of the hypothalamo-pituitary components of
      the HPG axis. In this study, we investigated the development of HPG axis function
      in the male transgenic growth retarded (Tgr) rat, a model of moderate systemic GH
      deficiency caused by hypothalamic expression of human (h)GH. Impaired postnatal
      somatotroph expansion and moderate GH deficiency in male Tgr rats were
      accompanied by a two- to three-fold increase in pituitary gonadotrophin content,
      but without a significant change in the pituitary gonadotroph population. A three
      to nine-fold elevation in basal circulating luteinising hormone concentration
      was seen in postpubertal Tgr rats, with a smaller increase in follicle
      stimulating hormone. Despite this hypergonadotrophism, there was no corresponding
      increase in steroidogenic (circulating testosterone and seminal vesicle weights)
      or gametogenic (spermatozoa counts in seminiferous tubules) activity in the
      postpubertal Tgr testis. Following puberty, the plasma leptin concentration also
      became progressively elevated in Tgr males. Circulating gonadotrophin and leptin
      levels were normalised in Tgr rats by peripheral physiological replacement of rat
      GH, but plasma testosterone concentration was unaffected. These results confirm
      that hGH exerts a positive influence on the central control of gonadotrophin
      secretion in the Tgr rat, but the absence of a corresponding elevation in the
      steroidogenic or gametogenic function of the Tgr testis implies that the
      peripheral GH/insulin-like growth factor I axis may also exert a permissive
      influence on testicular function. The relative contribution of somatogenic and
      lactogenic mechanisms and the potential influence of elevated leptin and
      decreased sensitivity to androgen feedback to the development of postpubertal
      hypergonadotrophism in Tgr males remain to be determined.

PMID- 16965291
TI  - Effect of chronic stress and mifepristone treatment on voltage-dependent Ca2+
      currents in rat hippocampal dentate gyrus.
AB  - Chronic unpredictable stress affects many properties in rat brain. In the dentate
      gyrus, among other things, increased mRNA expression of the Ca2+ channel alpha1C
      subunit has been found after 21 days of unpredictable stress in combination with
      acute corticosterone application (100 nM). In the present study, we examined: (i)
      whether these changes in expression are accompanied by altered Ca2+ currents in
      rat dentate granule cells recorded on day 22 and (ii) whether treatment with the
      glucocorticoid receptor antagonist mifepristone during the last 4 days of the
      stress protocol normalises the putative stress-induced effects. Three weeks of
      unpredictable stress did not affect Ca2+ current amplitude in dentate granule
      cells under basal conditions (i.e. after incubation with vehicle solution).
      However, the sustained Ca2+ current component (which largely depends on the
      alpha1C subunit) was significantly increased in amplitude after chronic stress
      when slices had been treated with corticosterone 1-4 h before recording. These
      findings suggest that dentate granule cells are exposed to an increased calcium
      load after exposure to an acute stressor when they have a history of chronic
      stress, potentially leading to increased vulnerability of the cells. The present
      results are in line with the molecular data on Ca2+ channel alpha1C subunit
      expression. A significant three-way interaction between chronic stress,
      corticosterone application and mifepristone treatment was found, indicating that
      the combined effect of stress and corticosterone depends on mifepristone
      cotreatment. Interestingly, current density (defined as total current divided by
      capacitance) did not differ between the groups. This indicates that the observed
      changes in Ca2+ current amplitude could be attributable to changes in cell size.

PMID- 16965292
TI  - Microinjection of galanin-like peptide into the medial preoptic area stimulates
      food intake in adult male rats.
AB  - Galanin-like peptide (GALP) is a neuropeptide implicated in the regulation of
      feeding behaviour, metabolism and reproduction. GALP is an endogenous ligand of
      the galanin receptors, which are widely expressed in the hypothalamus. GALP is
      predominantly expressed in arcuate nucleus (ARC) neurones, which project to the
      paraventricular nucleus (PVN) and medial preoptic area (mPOA).
      Intracerebroventricular or intraparaventricular (iPVN) injection of GALP acutely
      increases food intake in rats. The effect of GALP injection into the mPOA on
      feeding behaviour has not previously been studied. In the present study, intra
      mPOA (imPOA) injection of GALP potently increased 0-1-h food intake in rats. The
      dose-response effect of imPOA GALP administration on food intake was similar to
      that previously observed following iPVN administration. The effects of GALP (1
      nmol) or galanin (1 nmol) on food intake were then compared following injection
      into the PVN, mPOA, ARC, dorsal medial nucleus (DMN), lateral hypothalamus and
      rostral preoptic area (rPOA). GALP (1 nmol) increased food intake to a similar
      degree when injected into the imPOA or iPVN, but produced no significant effect
      when injected into the ARC, DMN, lateral hypothalamus or rPOA. Similarly, galanin
      (1 nmol) significantly increased food intake following injection imPOA and iPVN.
      However, the effect was significantly smaller than that following administration
      of GALP (1 nmol). Galanin also had no significant effect on food intake when
      administered into the ARC, DMN, lateral hypothalamus and rPOA. These data suggest
      that the mPOA and the PVN may have specific roles in mediating the orexigenic
      effect of GALP and galanin.

PMID- 16965293
TI  - Young adult-specific hyperphagia in diabetic Goto-kakizaki rats is associated
      with leptin resistance and elevation of neuropeptide Y mRNA in the arcuate
      nucleus.
AB  - The present study aimed to examine whether hyperphagia, which is frequently
      observed in type 1 diabetic patients and model animals, also occurs in type 2
      diabetic Goto-Kakizaki (GK) rats and, if so, to explore underlying abnormalities
      in the hypothalamus. GK rats at postnatal weeks 6-12, compared to control Wistar
      rats, exhibited hyperphagia, hyperglycaemia, hyperleptinemia and increased
      visceral fat accumulation, whereas body weight was unaltered. The ability of
      leptin to suppress feeding was reduced in GK rats compared to Wistar rats of
      these ages. In GK rats, leptin-induced phosphorylation of signal transducer and
      activator of transcription 3 was significantly reduced in the cells of the
      hypothalamic arcuate nucleus (ARC), but not of the ventromedial hypothalamus,
      whereas the mRNA level of functional leptin receptor was unaltered. By real-time
      polymerase chain reaction and in situ hybridisation, mRNA levels of neuropeptide
      Y, but not pro-opiomelanocortin and galanin-like peptide, were significantly
      increased in the ARC of GK rats at 11 weeks, but not 26 weeks. Following i.c.v.
      injection of a NPY Y1 antagonist, 1229U91, the amount of food intake in GK rats
      was indistinguishable from that in Wistar rats, thus eliminating the hyperphagia
      of GK rats. These results demonstrate that young adult GK rats display
      hyperphagia in association with leptin resistance and increased NPY mRNA level in
      the ARC.

PMID- 16965294
TI  - Involvement of the ser-glu-pro motif in ligand species-dependent desensitisation
      of the rat gonadotrophin-releasing hormone receptor.
AB  - There are two forms of gonadotrophin-releasing hormone (GnRH), GnRH-I and GnRH
      II, in the vertebrate brain. Both GnRH-I and GnRH-II are thought to interact with
      the type-I GnRH receptor (GnRHR). The present study attempted to demonstrate
      whether GnRH-I and GnRH-II induce differential desensitisation of GnRHR and to
      identify the motif involved. Time course inositol phosphate (IP) accumulation
      assay reveals that, in cells expressing the wild-type rat GnRHR, GnRH-I induced
      continuous increase in IP production, whereas GnRH-II-induced IP production rate
      at later time points (30-120 min after ligand treatment) became attenuated.
      However, in cells expressing the mutant receptor in which the Ser-Glu-Pro (SEP)
      motif in extracellular loop 3 was replaced by Pro-Glu-Val (PEV), IP accumulation
      rates at later time points were more decreased by GnRH-I than GnRH-II. Ca2+
      responses to repetitive GnRH applications reveal that GnRH-II desensitised the
      wild-type receptor faster than GnRH-I, whereas the opposite situation was
      observed in the PEV mutant. In addition, cell surface loss of GFP-tagged wild
      type receptor was more facilitated by GnRH-II than GnRH-I, whereas that of the
      GFP-tagged PEV mutant receptor was more enhanced by GnRH-I than GnRH-II. The
      present study indicates that the SEP motif is potentially responsible for ligand
      species-dependent receptor desensitisation. Together, these results suggest that
      GnRH-I and GnRH-II may have different effects on mammalian type-I GnRHR via
      modulation of desensitisation rates.

PMID- 16965295
TI  - Immunocytochemical detection of cholecystokinin and corticotrophin-releasing
      hormone neuropeptides in the hypothalamic paraventricular nucleus of the jerboa
      (Jaculus orientalis): modulation by immobilisation stress.
AB  - The hypothalamic response to an environmental stress implicates the
      corticotrophin-releasing hormone (CRH) neuroendocrine system of the hypothalamic
      parvicellular paraventricular nucleus (PVN) in addition to other neuropeptides
      coexpressed within CRH neurones and controlling the hypothalamo-pituitary-adrenal
      (HPA) axis activity as well. Such neuropeptides are vasopressin, neurotensin and
      cholecystokinin (CCK). It has previously been demonstrated that the majority of
      the CRH neuronal population coexpresses CCK after a peripheral stress in rats. In
      the present study, we explored such neuroendocrine plasticity in the jerboa in
      captivity as another animal model. In particular, we studied CCK and CRH
      expression within the hypothalamic PVN by immunocytochemistry in control versus
      acute immobilisation stress-submitted jerboas. The results show that CCK- and CRH
      immunoreactive neuronal systems are located in the hypothalamic parvicellular
      PVN. The number of CCK-immunoreactive neurones within the PVN was significantly
      increased (138% increase) in stressed animals compared to controls. Similarly,
      the number of CRH-containing neurones was higher in stressed jerboas (128%)
      compared to controls. These results suggest that the neurogenic stress caused by
      immobilisation stimulates CCK as well as CRH expression in jerboas, which
      correlates well with previous data obtained in rats using other stressors. The
      data obtained also suggest that, in addition to CRH, CCK is another neuropeptide
      involved in the response to stress in jerboa, acting by controlling HPA axis
      activity. Because CCK is involved in the phenotypical plasticity of CRH
      containing neurones in response to an environmental stress, we also explored
      their coexpression by double immunocytochemistry within the PVN and the median
      eminence (i.e. the site of CRH and CCK corelease in the rat) following jerboa
      immobilisation. The results show that CCK is not coexpressed within CRH neurones
      in either control or stressed jerboa, suggesting differences between jerboas and
      rats in the neuroendocrine regulatory mechanisms of the stress response involving
      CRH and CCK. The adaptative physiological mechanisms to environmental conditions
      might vary from one mammal species to another.

PMID- 16965296
TI  - Exaggerated response of arginine vasopressin-enhanced green fluorescent protein
      fusion gene to salt loading without disturbance of body fluid homeostasis in
      rats.
AB  - We examined the effects of chronic salt loading on the hypothalamic expressions
      of the enhanced green fluorescent protein (eGFP), arginine vasopressin (AVP) and
      oxytocin (OXT) genes in AVP-eGFP transgenic rats that expressed eGFP in the
      hypothalamic AVP-containing neurones. In these rats, salt loading for 5 days
      caused a marked increase of the eGFP fluorescence in the magnocellular divisions
      of the paraventricular nucleus (PVN), the supraoptic nucleus (SON) and the
      internal layer of the median eminence. Expression of the eGFP gene was increased
      seven- to eight-fold in the PVN and SON of salt-loaded rats in comparison with
      euhydrated rats. By contrast, none of these changes were observed in the
      suprachiasmatic nucleus. The expression of the AVP and OXT genes was increased
      1.5- to two-fold in the PVN and SON of salt-loaded nontransgenic (control) and
      transgenic rats. There were no differences in the expression levels of the AVP
      and OXT genes in the PVN and SON between nontransgenic (control) and transgenic
      animals under normal conditions and after salt loading. In the posterior
      pituitary gland, the intensity of the eGFP fluorescence did not change after salt
      loading for 5 days, but increased after 10 days of salt loading. Upon salt
      loading, significant increases in the plasma AVP concentrations, plasma
      osmolality and plasma Na+ were observed. Furthermore, there were no significant
      differences in changes of water intake, food intake, urine volume, urine
      osmolality, urine Na+ concentrations, and the body weights in both models under
      normal or salt-loaded conditions. Our results show that the response of the AVP
      eGFP fusion gene to chronic salt loading is exaggerated, and humoral responses
      such as AVP and OXT and the body fluid homeostasis are maintained in AVP-eGFP
      transgenic rats. The AVP-eGFP transgenic rat gives us a new opportunity to study
      the dynamics of the AVP system in vivo.

PMID- 16965297
TI  - Effects of oestrogen on cognition: what have we learned from basic research?
AB  - The results of clinical and basic research conducted over the past two decades
      have implicated a role for oestrogen in modulating cognitive function. This
      review focuses on what the results of research using female rodent models have
      revealed about the effects of oestrogen on mammalian cognition. Increased levels
      of oestrogen are associated with increased dendritic spine and synapse density in
      the hippocampus, a brain area important for learning and memory. However, the
      role of oestrogen in the modulation of performance on tasks of learning and
      memory is complex because it exerts enhancing effects on some tasks and impairing
      effects on others. Hypotheses have been offered to explain these varied actions,
      including differentiating the effects of oestrogen on cognitive processes
      required to complete tasks and analysing the influence of fluctuating levels of
      oestrogen on the strategies selected by animals to solve tasks. It is proposed
      that, when these hypotheses are viewed together and within the context of
      oestrogen action in the hippocampus and potentially other brain areas, a
      framework for understanding the varied effects of oestrogen on cognition emerges.
      The hippocampal-dependent memory system supports the flexible expression of
      memories and the hippocampal-independent memory system supports development of
      individual representations. Because of the effects exerted by oestrogen on the
      structure and function of the hippocampus, it would be expected to enhance
      performance across a variety of tasks that require hippocampal-dependent flexible
      expression of memories and would not enhance performance on tasks that involve
      hippocampal-independent individual representations. This review offers a
      theoretical model by which the divergent results of studies assessing the role of
      oestrogen on cognition can be reconciled and suggests that effects of oestrogen
      on cognition are best understood within the framework of oestrogen action in the
      brain and the role of those brain areas affected by oestrogen in the mediation of
      learning and memory.

PMID- 16965298
TI  - Localisation and physiological regulation of corticotrophin-releasing factor
      receptor 1 mRNA in the Xenopus laevis brain and pituitary gland.
AB  - In Xenopus laevis, corticotrophin-releasing factor (CRF) and urocortin 1 are
      present in the brain and they both are potent stimulators of alpha-melanophore
      stimulating hormone (MSH) secretion by melanotroph cells in the pituitary gland.
      Because both CRF and urocortin 1 bind with high affinity to CRF receptor type 1
      (CRF1) in mammals and Xenopus laevis, one of the purposes of the present study
      was to identify the sites of action of CRF and urocortin 1 in the Xenopus brain
      and pituitary gland. Moreover, we raised the hypothesis that the external light
      intensity is a physiological condition controlling CRF1 expression in the
      pituitary melanotroph cells. By in situ hybridisation, the presence of CRF1 mRNA
      is demonstrated in the olfactory bulb, amygdala, nucleus accumbens, preoptic
      area, ventral habenular nuclei, ventromedial thalamic area, suprachiasmatic
      nucleus, ventral hypothalamic area, posterior tuberculum, tectum mesencephali and
      cerebellum. In the pituitary gland, CRF1 mRNA occurs in the intermediate and
      distal lobe. The optical density of the CRF1 mRNA hybridisation signal in the
      intermediate lobe of the pituitary gland is 59.4% stronger in white-adapted
      animals than in black-adapted ones, supporting the hypothesis that the
      environmental light condition controls CRF1 mRNA expression in melanotroph cells
      of X. laevis, a mechanism likely to be responsible for CRF- and/or urocortin 1
      stimulated secretion of alpha-MSH.

PMID- 16965299
TI  - Elevated KiSS-1 expression in the arcuate nucleus prior to the cyclic
      preovulatory gonadotrophin-releasing hormone/lutenising hormone surge in the ewe
      suggests a stimulatory role for kisspeptin in oestrogen-positive feedback.
AB  - Kisspeptins are encoded by the gene KiSS-1 and regulate gonadotrophin-releasing
      hormone (GnRH) and gonadotrophin secretion in various species, including humans.
      Here, we quantify gene expression of KiSS-1 in the arcuate nucleus (ARC) across
      the ovine oestrous cycle and demonstrate an increase in the caudal division of
      the ARC during the preovulatory period. These data strongly suggest that
      kisspeptins are involved in the generation of the preovulatory GnRH and
      luteinising hormone surge.

PMID- 16965300
TI  - Lecturers' unions.

PMID- 16965301
TI  - Gilles Deleuze: psychiatry, subjectivity, and the passive synthesis of time.
AB  - Abstract Although 'modern' mental health care comprises a variety of theoretical
      approaches and practices, the supposed identification of 'mental illness' can be
      understood as being made on the basis of a specific conception of subjectivity
      that is characteristic of 'modernity'. This is to say that any perceived
      'deviation' from this characteristically 'modern self' is seen as a possible
      'sign' of 'mental illness', given a 'negative determination', and conceptualized
      in terms of a 'deficiency' or a 'lack'; accordingly, the 'ideal''therapeutic' aim
      of 'modern' mental health care can be understood as the 'rectification' of that
      'deficiency' through a 're-instatement' of the 'modern self'. Although
      contemporary mental health care is increasingly becoming influenced by the so
      called 'death' of the 'modern self', this paper will suggest that it is the work
      of the 20th century French philosopher, Gilles Deleuze, that is able to provide
      mental health care with a coherent determination of a 'post-modern self'.
      However, a Deleuzian account of subjectivity stands in stark contrast to
      'modernity's' conception of subjectivity and, as such, this paper will attempt to
      show how this 'post-modern' subjectivity challenges many of the assumptions of
      'modern' mental health care. Moreover, acknowledging the complexity and the
      perceived difficulty of Deleuze's work, this paper will provide an account of
      subjectivity that can be understood as 'Deleuzian' in its orientation, rather
      than 'Deleuze's theory of subjectivity', and therefore, this paper also seeks to
      stimulate further research and discussion of Deleuze's work on subjectivity, and
      how that work may be able to inform, and possibly even reform, the theoretical
      foundations and associated diagnostic and therapeutic practices of psychiatry,
      psychotherapy, and mental health nursing.

PMID- 16965302
TI  - Autonomy and autonomy competencies: a practical and relational approach.
AB  - This essay will address a general philosophical concern about autonomy, namely,
      that a conception of autonomy focused on freedom of the will alone is inadequate,
      once we consider the effects of oppressive forms of socialization on individuals'
      formation of choices. In response to this problem, I will present a brief
      overview of Diana Meyers's account of autonomy as relational and practical. On
      this view, autonomy consists in a set of socially acquired practical competencies
      in self-discovery, self-definition, self-knowledge, and self-direction. This
      account provides a distinction between choices that express unreflectively
      internalized social norms and those that are the result of a critical 'self
      reading'. I conclude that this practical conception of autonomy makes much higher
      demands upon nurses (and patients) than has previously been thought. In fact, if
      nurses are to be expected to genuinely promote autonomy, they are going to need
      specific training in counselling-type communication skills.

PMID- 16965303
TI  - Evidence for practice, epistemology, and critical reflection.
AB  - Evidence-based practice (EBP) has become a critical concept for ethical,
      accountable professional nursing practice. However, critical analysis of the
      concept suggests that EBP overemphasizes the value of scientific evidence while
      underplaying the role of clinical judgement and individual nursing expertise.
      This paper explores the empiricist position that valid evidence is the basis for
      all knowledge claims. We argue against the positivist idea that science should be
      regarded as the only credible means for generating evidence on which to base
      knowledge claims. We propose that the process of critically reflecting on
      evidence is a fundamental feature of empirical epistemology. We suggest that
      critical reflection on evidence derived from science, arts and humanities and, in
      particular, nursing practice experience can provide a sound basis for knowledge
      claims. While we do not attempt to define what counts as evidence, it is argued
      that there is much to be gained by making the processes of critical reflection
      explicit, and that it can make a valid contribution to expert nursing practice,
      without recourse to irreducible concepts such as intuition.

PMID- 16965304
TI  - The nature of care in light of Emmanuel Levinas.
AB  - The discipline of nursing is still struggling with the differences that need to
      be clearly defined between the notions of care and nursing care. To be able to
      clarify this distinction, agreement must first be reached on the meaning of care
      itself. The present article proposes a conception of care in light of the
      philosophy of Emmanuel Levinas (1906-1995). This philosopher's thought throws
      considerable light on the ontology of care, thanks especially to his focus on the
      deeper implications of human encounter. A profound sense of responsibility
      towards the other enables Levinas to bring out such dimensions of the concept of
      care as the relation involved, the feeling of affection, and the interventions.
      We examine here what these entail regarding nursing care.

PMID- 16965305
TI  - The phenomenology of life phenomena--in a nursing context.
AB  - The purpose of this article is to describe and develop knowledge about life
      phenomena in a life-philosophical and nursing context. Knowledge about life
      phenomena is part of a care-ethical understanding with a focus on relations. Life
      phenomena are to be understood as a generalized label for the various phenomena
      which are given with human existence. The Danish life philosophical tradition
      with the perspective of life as experienced has something to say in relation to a
      further refinement of the phenomenology of life phenomena. The refinement will be
      described as an ethical and existential understanding of the phenomena of
      nursing. The first part of the article takes a philosophical approach to the
      phenomenology of life phenomena. It attempts to locate life phenomena in relation
      to, respectively, needs, senses, and feelings. In order to maintain an overview,
      the attempt is made to separate needs, senses, and feelings, although in real
      life these are closely interwoven. The article also describes philosophy and life
      phenomena in relation to nursing as an empirical field. In nursing there is a
      risk that life phenomena become invisible to those whose task is to help the ill
      person adjust to a new life situation. For the nurse, it will be a continuing
      task, never completed, to develop a sensory-based, situation-determined attention
      to the patient. And the nurse must be continually aware of whether mere 'need
      oriented' nursing is controlling her professional actions as a nurse. Taking a
      point of departure in the nurse's sensory, situationally determined attention,
      the last part of the article focuses on needs, senses, and feelings in connection
      with the nurse being able to direct her attention to the patient's life
      phenomena.

PMID- 16965306
TI  - Intelligent nursing: accounting for knowledge as action in practice.
AB  - This paper provides an analysis of nursing as a knowledgeable discipline. We
      examined ways in which knowledge operates in the practice of home care nursing
      and explored how knowledge might be fruitfully understood within the ambiguous
      spaces and competing temporalities characterizing contemporary healthcare
      services. Two popular metaphors of knowledge in nursing practice were identified
      and critically examined; evidence-based practice and the nurse as an intuitive
      worker. Pointing to faults in these conceptualizations, we suggest a different
      way of conceptualizing the relationship between knowledge and practice, namely
      practice as being activated by contextualized knowledge. This conceptualization
      is captured in an understanding of the intelligent creation of context by the
      nurse for nursing practice to be ethical and effective.

PMID- 16965307
TI  - Facilitating the development of moral insight in practice: teaching ethics and
      teaching virtue.
AB  - Abstract The teaching of ethics is discussed within the context of insights
      gleaned from ancient Greek ethics, particularly Aristotle and Plato and their
      conceptions of virtue (arete, meaning excellence). The virtues of excellence of
      character (moral virtue) and excellence of intelligence (intellectual virtue),
      particularly practical wisdom and theoretical wisdom, are considered. In
      Aristotelian ethics, a distinction is drawn between these intellectual virtues:
      experience and maturity is needed for practical wisdom, but not for theoretical
      wisdom. In addition to this, excellence of character is acquired through habitual
      practice, not instruction. This suggests that there is a need to teach more than
      theoretical ethics and that the ethics teacher must also facilitate the
      acquisition of practical wisdom and excellence of character. This distinction
      highlights a need for various educational approaches in cultivating these
      excellences which are required for a moral life. It also raises the question: is
      it possible to teach practical wisdom and excellence of character? It is
      suggested that virtue, conceived of as a type of knowledge, or skill, can be
      taught, and people can, with appropriate experience, habitual practice, and good
      role models, develop excellence of character and become moral experts. These
      students are the next generation of exemplars and they will educate others by
      example and sustain the practice of nursing. They need an education which
      includes theoretical ethics and the nurturing of practical wisdom and excellence
      of character. For this purpose, a humanities approach is suggested.

PMID- 16965308
TI  - Marcelian charm in nursing practice: the unity of agape and eros as the
      foundation of an ethic of care.
AB  - In the nursing literature, a number of qualities are associated with loving care.
      Reference is made to, among other things, humility, attentiveness, responsibility
      and duty, compassion, and tenderness. The author attempts to show that charm, in
      the Marcelian sense, also plays a central role. It is argued that the moral
      foundation of charm is a unity of agape and eros. An impartial giving of the self
      for others is clearly of fundamental importance in an ethic of care. Including
      charm in the discussion points to the fact that eros also plays a crucial role.
      Eros produces a passion for people and for life. It is a physical and spiritual
      energy that animates a person in all facets of her life, including her caring
      work.

PMID- 16965310
TI  - Calling all educators to teach and model evidence-based practice in academic
      settings.

PMID- 16965311
TI  - Evidence, virulence, and the disappearance of nursing knowledge: A critique of
      the evidence-based dogma.
AB  - CONTEXT: Within the domain of health care, the new discourse of evidence-based
      practice has appeared and gained momentum, giving rise to a plethora of
      correlates such as specialized scientific journals and best practice guidelines.
      Following the crowd, nursing has jumped onto this trend's bandwagon. Although
      some scholars and clinicians have tried to expand these notions, few have
      considered a deconstructive approach to do so. APPROACH: Drawing on the works of
      continental postmodern thinkers such as Baudrillard, Deleuze & Guattari, and
      Foucault, this paper critically examines the rise of the evidence-based nursing
      (EBN) movement in order to deconstruct the "taken-for-granted" assumption that
      EBN is in and of itself the favored path to the sound development of nursing
      knowledge. DISCUSSION: We argue against the hierarchical differentiation of
      varied research approaches so as to allow diverse methodologies to guide research
      and ultimately practice. The status quo is challenged, where research agendas are
      currently dominated by one paradigm of knowledge development; that of post
      positivism in which randomized control trials are portrayed as superior evidence.
      There is a hazard in excluding many other venues to build nursing knowledge and
      in oversimplifying the complexity of clinical nursing practice. Furthermore, we
      argue that this preferred path of knowledge development contradicts nursing
      academics' efforts to distance itself from the medical model of health care
      provision and research.

PMID- 16965312
TI  - Research awareness: An important factor for evidence-based practice?
AB  - BACKGROUND: Despite the growing body of literature, the reality of getting
      evidence into practice remains problematic. OBJECTIVE: The purpose of this study
      was to establish levels of research awareness amongst registered health care
      professionals (RHCPs) and the influence of research awareness on evidence-based
      practice activities. DESIGN AND METHODS: This was a descriptive quantitative
      study. A convenience sample of 2,126 registered RHCPs working in a large acute
      hospital in Northeast England, the United Kingdom was used. A self-completion
      Research Awareness Questionnaire (RAQ) was directed towards measuring RHCP:
      attitudes towards research, understanding of research and the research process,
      and associations with practising using an evidence base. Data were entered into a
      Statistical Package for Social Science (SPSS) database and descriptive and
      inferential statistics were used. FINDINGS: A total of 843 questionnaires were
      returned. Seven hundred and thirty-three (91%) RHCPs overwhelmingly agreed with
      the principle that evidence-based practice has a large part to play in improving
      patient care. This point was reinforced by 86% (n = 701) of respondents strongly
      agreeing or agreeing with the idea that evidence-based practice is the way
      forward to change clinical practice. Significant associations were noted between
      levels of confidence to undertake a piece of research and whether the individual
      had received adequate information about the research process, had basic knowledge
      and understanding of the research process, or had research awareness education or
      training. CONCLUSIONS: The study shows that RHCPs, regardless of position or
      grade, have a positive attitude towards research but face many obstacles. The key
      obstacles are lack of time, support, knowledge, and confidence. To address these
      obstacles, it is imperative that the organisation adopts a structured and
      coordinated approach to enable and empower individuals to practice using an
      evidence base.

PMID- 16965313
TI  - Eliciting patient treatment preferences: A strategy to integrate evidence-based
      and patient-centered care.
AB  - BACKGROUND: The integrated patient-centered evidence-based approach to care is
      integral to guide practice and enhance the quality of care. In this paper, a
      strategy to operationalize the integrated approach is described. DESCRIPTION OF
      STRATEGY: The strategy flows from the processes used to synthesize the best
      available evidence for interventions that address a clinical problem, and to
      elicit patient preferences for treatment options, which is an important step in
      patient-centered care. The strategy consists of three phases: (1) synthesis of
      evidence about the effectiveness and relevance of interventions derived from
      research and practice; (2) generation of written material describing the nature,
      dose, effectiveness, and risks associated with the evidence-based interventions;
      and (3) using the written descriptions to elicit patient preferences. Examples
      from an ongoing study are presented to illustrate the implementation of the
      strategy within the context of research. IMPLICATIONS: Nurses are invited to
      apply the strategy in practice and to evaluate its feasibility and utility in
      enhancing the quality of care.

PMID- 16965314
TI  - Forecasting: Adopting the methodology of support vector machines to nursing
      research.

PMID- 16965317
TI  - The laminopathies: a clinical review.
AB  - The laminopathies are a diverse group of conditions caused by mutations in the
      LMNA gene (MIM*150330). LMNA encodes the nuclear envelope proteins lamin A and
      lamin C by utilization of an alternative splice site in exon 10. The human LMNA
      gene was identified in 1986 but it was another 13 years before it was found to be
      the causative gene for a disease, namely Emery Dreifuss muscular dystrophy. Since
      then, a further eight clearly defined phenotypes have been associated with LMNA
      mutations. The diversity of these phenotypes is striking with features such as
      premature ageing, axonal neuropathy, lipodystrophy and myopathy being seen. These
      phenotypes and the emerging genotype/phenotype correlations are the subject of
      this review.

PMID- 16965318
TI  - Heterozygosity for a Mendelian disorder as a risk factor for complex disease.
AB  - While genetic diseases are generally classified as being either 'simple'
      monogenic or 'complex' polygenic, the distinction between Mendelian and complex
      disorders is becoming increasingly blurred. Mendelian disorders may demonstrate
      qualities more typical of multifactorial diseases through shared clinical
      presentations, the effect of genetic modifiers, moonlighting proteins,
      synergistic heterozygosity, disease manifestations in heterozygotes and
      situations where heterozygosity for a 'simple' disorder proves to be a risk
      factor for seemingly unrelated complex diseases. A recent example of the last
      instance is the observation that mutations in glucocerebrosidase, the enzyme
      deficient in Gaucher disease, may be a risk factor for the development of
      Parkinson disease and other synucleinopathies. Insights gleaned from the study of
      Mendelian disorders may ultimately lead to a better understanding of factors
      influencing complex diseases.

PMID- 16965319
TI  - Predictive testing for Huntington disease: interpretation and significance of
      intermediate alleles.
AB  - Direct mutation analysis for Huntington disease (HD) became possible in 1993 with
      the identification of an expanded CAG trinucleotide repeat as the mutation
      underlying the disease. Expansion of CAG length beyond 35 repeats may be
      associated with the clinical presentation of HD. HD has never been seen in a
      person with a CAG size of <36 repeats. Intermediate alleles are defined as being
      below the affected CAG range but have the potential to expand to >35 CAG repeats
      within one generation. Thus, children of intermediate allele carriers have a low
      risk of developing HD. Currently, the intermediate allele range for HD is between
      27 and 35 CAG repeats. In this study, we review the current knowledge on
      intermediate alleles for HD including the CAG repeat range, the intermediate
      allele frequency, and the clinical implications of an intermediate allele
      predictive test result. The factors influencing CAG repeat expansion, including
      the CAG size of the intermediate allele, the sex and age of the transmitting
      parent, the family history, and the HD gene sequence and haplotype, will also be
      reviewed.

PMID- 16965320
TI  - Developmental programming of hypothalamic feeding circuits.
AB  - The hypothalamus plays a critical role in the regulation of food intake and body
      weight, and recent work has defined a core circuitry in the hypothalamus that
      appears to mediate many of the effects of the adipocyte-derived hormone leptin on
      feeding and glucose homeostasis. However, until recently, little was known about
      the development of these critical pathways. This review summarizes recent
      advances regarding the post-natal development of 'metabolic' projections from the
      arcuate nucleus of the hypothalamus. Evidence accumulated primarily in mice
      indicates that these circuits develop after birth and remain both structurally
      and functionally immature until the second week of life. Recent studies have
      begun to identify cues governing development of these pathways, and leptin
      appears to play a crucial neurotrophic role in the development of the
      hypothalamic circuits regulating food intake and adiposity. The
      neurodevelopmental actions of leptin appear specifically to be restricted to a
      neonatal critical period that coincides with the naturally occurring surge in
      leptin. In addition, the timing and amplitude of the post-natal leptin surge has
      important consequences for normal body weight regulation and glucose homeostasis
      later in life. Ultimately, these data promise to provide new insight into the
      mechanisms by which alteration of perinatal nutrition may have long-term
      consequences on body weight regulation and adiposity in the offspring.

PMID- 16965321
TI  - Stem cell research: cloning, therapy and scientific fraud.
AB  - Stem cell research has generated intense excitement, awareness, and debate.
      Events in the 2005-2006 saw the rise and fall of a South Korean scientist who had
      claimed to be the first to clone a human embryonic stem cell line. From
      celebration of the potential use of stem cells in the treatment of human disease
      to disciplinary action taken against the disgraced scientists, the drama has
      unfolded throughout the world media. Prompted by an image of therapeutic cloning
      presented on a South Korean stamp, a brief review of stem cell research and the
      events of the Woo-suk Hwang scandal are discussed.

PMID- 16965325
TI  - Variability and inequity in testing of somatic tissue for hereditary cancer: a
      survey of UK clinical practice.
AB  - A growing body of literature demonstrates the benefits of molecular pathological
      investigations of tumour material in the identification of individuals with
      hereditary non-polyposis colorectal cancer and debates the best detection
      strategies. This testing is novel as it is the first widespread use of somatic
      tissue testing to inform genetic analysis and requires the co-ordination of both
      histopathology and molecular genetics laboratories. However, the clinical use and
      experience of microsatellite instability (MSI) testing and immunohistochemical
      analysis have not been reported. A respondent from every cancer genetics centre
      in the UK (n= 24, response rate 100%) and laboratory performing MSI testing (n=
      5, response rate 100%) was interviewed by telephone to ascertain test
      availability, testing methods, eligibility criteria and post-test management.
      Twenty centres (83%) offer eligible clients at least one form of tumour testing,
      and all use tumour testing to determine who should have access to germ line
      genetic testing. However, no two laboratories used the same testing methods,
      seven different testing strategies were applied and there was considerable
      variation in eligibility criteria. The implications of these variations are
      considered, and recommendations for the development of a consistent service for
      testing of somatic tissue offered.

PMID- 16965326
TI  - Application of BRCA1 and BRCA2 mutation carrier prediction models in breast
      and/or ovarian cancer families of French Canadian descent.
AB  - The BRCAPRO, Couch, Myriad I and II, Ontario Family History Assessment Tool
      (FHAT), and Manchester models have been used to predict BRCA1 or BRCA2 mutation
      carrier status of women at high risk for developing the heritable form of breast
      and ovarian cancers. We have evaluated these models for their accuracy in
      classifying 224 French Canadian families with at least three cases of breast
      cancer (diagnosed before the age of 65 years), ovarian cancer, or male breast
      cancer where mutation status was known for an index affected case used to assess
      the model. This series includes 44 BRCA1 and 52 BRCA2 mutation-positive families.
      Using receiver operator characteristics analyses, the C-statistics were found to
      be 0.81, 0.80, 0.79, and 0.74 for the BRCAPRO, FHAT, Manchester, and Myriad II
      models, respectively, when incorporating both BRCA1 and BRCA2 mutation carrier
      predictions. For the BRCAPRO model, 75% scored greater than a 0.43 probability in
      the mutation-positive group and 75% scored less than 0.50 in the mutation
      negative group. Only 38 of 128 (30%) mutation-negative group had a probability
      greater than 0.43 with the BRCAPRO model. While all models were highly predictive
      of carrier status, the BRCAPRO model was the most accurate where a cut-off of 10%
      would have eliminated 60 of 128 (47%) mutation-negative families for genetic
      testing and only miss 10 of 96 (10%) mutation-positive families. A review of the
      cancer phenotypes with high BRCAPRO probabilities showed that significantly more
      metachronous bilateral breast cancer cases occurred in BRCA1/2 mutation carrier
      families in comparison to mutation-negative families, a feature which is not
      discriminated in the BRCAPRO model.

PMID- 16965327
TI  - Hereditary lymphedema type I associated with VEGFR3 mutation: the first de novo
      case and atypical presentations.
AB  - Mutations in the vascular endothelial growth factor receptor 3 gene, VEGFR3/FLT4,
      have been identified in a subset of families with hereditary lymphedema type I or
      Milroy disease (MIM 153100). Individuals carrying a VEGFR3 mutation exhibit
      congenital edema of the lower limbs, usually bilaterally and below the knees,
      sometimes associated with cellulitis, prominent veins, papillomatosis, upturned
      toenails, and hydrocele. In this study, we report the first de novo VEGFR3
      mutation in a patient with sporadic congenital lymphedema. We also describe three
      other families with a VEGFR3 mutation. In each family, one individual had an
      atypical clinical presentation of hereditary lymphedema type I, whereas the
      others had the classical VEGFR3 mutation-caused phenotype. The atypical
      presentations included pre-natal pleural effusion, spontaneous resorption of
      lymphedema and elephantiasis. Three of the four identified mutations were novel.
      These data show that de novo VEGFR3 mutations may be present in patients without
      family history of congenital lymphedema. This has implications for follow-up
      care, as such individuals have nearly a 50% risk for occurrence of lymphedema in
      their children. Our findings also indicate that although most patients with a
      VEGFR3 mutation have the well-defined phenotype for hereditary lymphedema type I,
      there are exceptions that should be considered in genetic counseling. Because
      VEGFR3 mutation can cause generalized lymphatic dysfunction and can thus result
      in hydrops fetalis, VEGFR3 screening should be added to the investigation of
      cases of hydrops fetalis of an unknown etiology.

PMID- 16965328
TI  - Germline mosaicism for a MECP2 mutation in a man with two Rett daughters.
AB  - Rett syndrome is a severe neurodevelopmental disorder that is caused by mutations
      in the X-linked gene, methyl-CpG binding protein 2 (MECP2). The majority of cases
      are sporadic, but rarely germline mosaicism can lead to familial cases. Here, we
      report the first case where germline mosaicism for a MECP2 mutation has been
      shown in a man. He has two affected daughters who are half sisters, and both have
      the c.808delC mutation. We show that this mutation is present at a low level in
      DNA extracted from the patient's semen. This case has implications for genetic
      counseling, and pre-natal testing should be offered for the partners of men who
      have a daughter with Rett syndrome.

PMID- 16965329
TI  - Dystrophic epidermolysis bullosa pruriginosa in Italy: clinical and molecular
      characterization.
AB  - Dystrophic epidermolysis bullosa (DEB) pruriginosa (DEB-Pr) is a rare variant of
      DEB due to COL7A1 dominant and recessive mutations, which is characterized by
      severe itching and lichenoid or nodular prurigo-like lesions, mainly involving
      the extremities. Less than 30 patients have been described showing variable
      disease expression, and frequently, delayed age of onset. We report the clinical
      and molecular characterization of seven Italian DEB patients, three affected with
      recessive DEB-Pr and four with dominant DEB-Pr. In all the patients, the signs
      were typical of a mild DEB phenotype, until the onset of pruritus, which was
      followed by worsening of the clinical picture, with appearance of the distinctive
      lichenified lesions of DEB-Pr. Nine mutations were found in the COL7A1 gene,
      three of which were novel and one was de novo. DEB-Pr patients with either
      dominant or recessive mutations were shown to synthesize a normal or variably
      reduced amount of type VII collagen, which was correctly deposited at the dermal
      epidermal junction. Since six of these mutations have been reported in DEB
      patients in the absence of intense pruritus, these data implicate a role of yet
      unidentified phenotype-modifying factors in the pathogenesis of DEB-Pr.

PMID- 16965330
TI  - Molecular background of polyendocrinopathy-candidiasis-ectodermal dystrophy
      syndrome in a Polish population: novel AIRE mutations and an estimate of disease
      prevalence.
AB  - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an
      autosomal-recessive autoimmune disease caused by autoimmune regulator gene
      mutations. The aim of this study was to examine the mutation profile of Polish
      APECED patients, determine the carrier rate of the most frequent mutation(s) and
      estimate disease prevalence. While studying 14 unrelated patients, we identified
      three novel mutations (c.1A>T, affecting the start codon; [IVS1 + 1G>C; IVS1 +
      5delG], a complex mutation affecting splice site; c. 908G>C, p.R303P, a missense
      mutation in plant homeodomain (PHD) and three previously reported mutations
      (c.769C>T, p.R257X; c.967_979del13bp, C322fsX372; c.931delT, p.C311fsX376).
      Eleven patients had mutations on both chromosomes, whereas in three patients only
      a single alteration with proven or likely pathogenic effect was detected. The
      most frequent was the p.R257X mutation (71% of chromosomes); its carriage rate
      was assessed in the background population. Analysis of 2008 samples showed eight
      heterozygotes, indicating the frequency of 0.40% (1:250) and the disease
      prevalence - 1:129,000 (95% confidence interval: 1:555,000 to 1:30,000).
      Comparison with an epidemiological estimate (1:619,000, derived for women)
      suggested that in Poland, APECED is underdiagnosed. Among the patients, no
      genotype/phenotype correlations were found, but we noted that women had earlier
      onset of hypoparathyroidism (p < 0.02) and were younger at diagnosis (p < 0.05)
      than men.

PMID- 16965331
TI  - Identification of novel and recurrent glucokinase mutations in Belgian and
      Luxembourg maturity onset diabetes of the young patients.

PMID- 16965332
TI  - A frameshift mutation in peroxisome-proliferator-activated receptor-gamma in
      familial partial lipodystrophy subtype 3 (FPLD3; MIM 604367).

PMID- 16965333
TI  - Chromogenic in situ hybridization analysis of melastatin mRNA expression in
      melanomas from American Joint Committee on Cancer stage I and II patients with
      recurrent melanoma.
AB  - OBJECTIVE: To determine whether loss of melastatin (MLSN) is a universal
      phenomenon in American Joint Committee on Cancer (AJCC) stage I and II melanoma
      patients who experienced recurrence. MATERIAL AND METHODS: Paraffin blocks of
      primary melanomas (PMs) were retrieved from 30 patients who had a negative
      sentinel lymph node biopsy and developed recurrent melanoma (AJCC stage I and
      II). Chromogenic in situ hybridization (CISH) methods were utilized to evaluate
      the expression of MLSN mRNA. These results were correlated with clinicopathologic
      data. RESULTS: Variable, heterogeneous expression of MLSN mRNA was identified in
      normal, in situ and invasive melanocytes within and between cases. For the
      invasive PM component, 24 (80%) had focal, regional or complete loss of MLSN
      mRNA. The remaining 20% had either regional or total partial downregulation of
      MLSN mRNA. Intact MLSN mRNA expression was present regionally in 14/30 (47%),
      with mean relative tumor area of 38%, range 5-85%. Increasing loss of MLSN mRNA
      significantly correlated with increasing tumor depth and microsatellites (r =
      0.1/0.4, p = 0.04). However, thin, AJCC T stage 1a PM had higher relative mean
      loss than intermediate AJCC T stage 2a/2b/3a thickness PM (65% vs. 34%/48%/25%).
      Increasing loss of MLSN mRNA significantly impacted on disease free survival
      (DFS) by multivariate analysis (58 vs. 0% 2 years DFS, < or = 75 vs. > 75% mRNA
      loss, p = 0.02). Decreased overall survival significantly correlated with
      increasing age and vascular invasion on multivariate analysis. CONCLUSION:
      Extensive loss of MLSN in PM correlated with aggressive metastatic melanoma.
      Ancillary testing for MLSN mRNA expression by CISH could offer a means to more
      accurately identify AJCC stage I and II patients at risk for metastatic disease,
      who could benefit from adjuvant therapy.

PMID- 16965334
TI  - Overexpression of MLH-1 and psoriasin genes in cutaneous angiofibromas from
      tuberous sclerosis complex patients.
AB  - BACKGROUND: Tuberous sclerosis complex (TSC) is associated with mutations in two
      likely tumor-suppressor genes (TSC1 and TSC2) and characterized by the
      development of tumor-like growths (angiofibromas) in a variety of tissues and
      organs, particularly brain and skin. METHODS: Employing a DNA-microarray assay,
      able to detect mRNA production from 1176 different basic genes, we analyzed the
      gene-expression levels in a cutaneous hamartoma sample from a TSC patient.
      Altered gene expressions detected by microarray technology were further checked
      by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) in the
      same material and in cutaneous hamartoma samples obtained from five other TSC
      patients. RESULTS: The results obtained by the microarray technology in one
      hamartoma specimen, confirmed by the RT-PCR results obtained in the same material
      and in five other hamartoma specimens, demonstrated that TSC-related
      angiofibromas exhibit significant mRNA overexpression of two genes, represented
      by MLH-1 and psoriasin. CONCLUSIONS: The overexpression of MLH-1, which codes for
      a DNA mismatch repair protein, and psoriasin, which codes for a specific
      chemoattractant factor for CD4+ T cells, implicated in the pathogenesis of
      inflammatory skin disease, and expressed in excess during abnormal pathways of
      cell growth, may shed light on the pathogenesis of the proliferative skin lesion.

PMID- 16965335
TI  - Procollagen 1 - a marker of fibroblastic and fibrohistiocytic skin tumors.
AB  - BACKGROUND: When dealing with tumors of presumed fibroblastic or fibrohistiocytic
      origin, immunohistochemistry is traditionally done to exclude a tumor of non
      fibroblastic or non-fibrohistiocytic nature, because a reliable marker of
      fibroblastic or fibrohistiocytic cell origin is still to be introduced. This
      study investigates whether procollagen 1 is a useful marker of skin tumors
      composed of cells derived from fibroblasts or fibrohistiocytes. MATERIALS AND
      METHODS: Twenty-nine different types of skin tumors, including tumors composed of
      spindle cells as well as some additional epithelial and melanocytic tumors, were
      stained immunohistochemically with antibodies against procollagen 1. The total
      number of cases tested was 154. RESULTS: Tumors composed of cells of fibroblastic
      or fibrohistiocytic origin in general showed a high expression of procollagen 1,
      whereas tumors composed of non-fibroblastic cells in general showed no
      expression. However, there were a few exceptions, e.g., leiomyosarcoma and
      desmoplastic melanoma. CONCLUSIONS: The study suggests that immunohistochemical
      staining for procollagen 1 is a valuable marker for skin tumors composed of
      spindle cells derived from fibroblasts or fibrohistiocytes. However, in cases of
      spindle cell tumors with a morphology suggesting malignancy, it is recommended to
      use a panel of antibodies, which besides procollagen 1 includes markers such as
      S100, CD68, CD34, h-caldesmon, and pancytokeratin.

PMID- 16965336
TI  - Clusterin expression in primary and metastatic melanoma.
AB  - Clusterin is a pleiotrophic glycoprotein that has been implicated in diverse
      physiologic processes. Recent studies of gene expression profiling found
      clusterin to be expressed in desmoplastic variants of malignant melanoma. In this
      study, we extended those observations and examined clusterin expression in a
      larger number of primary as well as in metastatic melanomas and melanocytic nevi.
      We used tissue microarray panels as well as selected conventional sections from
      formalin-fixed and paraffin-embedded tissue blocks. Positive staining for
      clusterin was found in seven of 21 (30%) primary desmoplastic and three of 21
      (7%) non-desmoplastic melanoma. Among metastatic tumors, clusterin expression was
      found in five of 37 tumors (13.5%). Clusterin expression was not seen in
      melanocytes of normal skin or in any of the 10 melanocytic nevi tested. Clusterin
      expression was not entirely restricted to melanoma; it was also seen in a few non
      neoplastic tissues, including perifollicular fibroblasts, occasional sebocytes,
      and the epithelial cells lining sebaceous duct and the isthmus of the hair
      follicle. Our findings confirm the observation that clusterin can be expressed in
      melanoma, in particular primary desmoplastic melanoma. However, clusterin appears
      to be present only in a minority of melanomas.

PMID- 16965337
TI  - No evidence of Epstein-Barr virus association with Merkel cell carcinoma.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive tumor of cutaneous
      neuroendocrine cells with a reported 13-fold increased incidence in
      immunocompromised patients, raising the possibility that it is driven by an
      oncogenic virus. Additionally, Merkel cell hyperplasia is seen in the Epstein
      Barr virus (EBV)-driven process oral hairy leukoplakia, and EBV is known to be
      involved in the pathogenesis of several other malignancies. OBJECTIVE: We tested
      the hypothesis that EBV is involved in MCC. METHODS: We employed EBV-encoded RNA
      in situ hybridization (ISH), lytic EBV ISH, latent membrane protein 1
      immunohistochemistry, and BamH1Z leftward reading frame 1 immunohistochemistry to
      detect and localize EBV in paraffin sections of MCC from five patients as well as
      seven other cutaneous tumors and positive controls for EBV infection. RESULTS:
      Positive controls reacted appropriately. However, there was no evidence of latent
      or lytic EBV in any of the MCC biopsies or other cutaneous tumors. CONCLUSION:
      Our findings suggest that EBV is not associated with MCC.

PMID- 16965338
TI  - Correlation of p16 and pRb expression with HPV detection in Bowen's disease.
AB  - BACKGROUND: Bowen's disease is a form of cutaneous squamous cell carcinoma which
      may be caused by ultraviolet radiation, human papilloma virus (HPV) infection, or
      other causes. Although p16 over-expression is a surrogate marker of HPV E7
      mediated catabolism of pRb in premalignant and malignant lesions of the cervical
      mucosa, the correlation of p16 and pRb expression with HPV detection in Bowen's
      disease has not been well characterized. METHODS: A retrospective study on
      formalin-fixed tissues was performed. Immunohistochemistry for p16 and pRb was
      performed on 32 cases. DNA was successfully extracted from 20 cases, and
      polymerase chain reaction was performed to amplify a highly conserved region of
      the HPV L1 open reading frame. RESULTS: Twenty-eight of 32 (88%) cases showed
      strong diffuse staining for p16 but were negative for pRb; two of 32 cases (6%)
      were negative for p16 but were diffusely positive for pRb; one case was strongly
      positive for both p16 and pRb, and one case was negative for both p16 and pRb.
      Three of 20 cases (15%) contained HPV DNA. All three of these cases showed strong
      p16 expression and lack of pRb staining. CONCLUSIONS: Most cases of Bowen's
      disease strongly express p16 but not pRb. In contrast to HPV-associated lesions
      of the cervical mucosa, p16 overexpression in cutaneous Bowen's disease appears
      to be unrelated to HPV status. The p16 overexpression in Bowen's disease may
      reflect disruption of the G1/S checkpoint, resulting in unregulated cell cycle
      progression.

PMID- 16965339
TI  - Cytokeratin 15 expression in neoplasms with sebaceous differentiation.
AB  - BACKGROUND: Recent studies have demonstrated that the cytokeratin 15 (CK15)
      positive stem cells located in the hair follicle bulge are also involved in
      sebaceous gland renewal. No previous studies have dealt with the CK15 expression
      in sebaceous neoplasms. METHODS: We studied the CK15 expression in 30 sebaceous
      neoplasms including 10 sebaceomas (sebaceoma defined as a distinct benign
      neoplasm with sebaceous differentiation), 10 sebaceous neoplasms of Muir-Torre
      syndrome, and 10 sebaceous carcinomas, in addition to that in the mantles of
      normal hair follicles. RESULTS: CK15 was positive in the undifferentiated
      sebocytes of the mantles. All 10 sebaceomas showed CK15 expression in the
      basaloid, germinative cells. Both sebaceous neoplasms in Muir-Torre syndrome and
      sebaceous carcinomas demonstrated negative or only a focal positive reaction,
      including the occasional aberrant expression in matured sebocytes, to CK15.
      CONCLUSIONS: CK15 may be a useful marker for stem cells with a sebaceous fate,
      and a constant CK15 expression in sebaceomas supported the hypothesis that
      sebaceoma is a benign neoplasm of sebaceous germinative cells in the mantles. The
      similar staining pattern of CK15 between sebaceous neoplasms in Muir-Torre
      syndrome and sebaceous carcinomas may be one piece of evidence supporting the
      hypothesis that most sebaceous neoplasms in Muir-Torre syndrome are low-grade
      sebaceous carcinomas.

PMID- 16965340
TI  - Fli-1 expression in mycosis fungoides.
AB  - BACKGROUND: The Fli-1 transcription factor functions in cellular proliferation
      and tumorigenesis. Its role in various neoplasms and its presence in lymphocytes
      suggest a link between Fli-1 dysregulation and the pathogenesis of mycosis
      fungoides (MF). In this study, we further elucidate this possible link. METHODS:
      Sections from archived specimens were stained using a polyclonal antibody against
      Fli-1. The percentage of nuclei showing Fli-1 expression was recorded. These were
      compared with reactive dermatoses. RESULTS: All of the tumor stage lesions showed
      high levels of nuclear Fli-1 expression. Of plaque stage lesions, six of 12 (50%)
      showed the same intensity, while the remaining six of 12 varied significantly in
      their Fli-1 expression. The few patch stage lesions also showed varied
      expression. CONCLUSION: This study shows diffuse nuclear expression of Fli-1 in
      all tumor stage MF, whereas expression of this transcription factor varied widely
      in the early, epidermotropic stages. Although the numbers are too small to draw
      statistical significance, this study demonstrates an association between
      increased expression of Fli-1 and progression to tumor stage MF that merits
      further investigation. Additionally, the mixed expression of Fli-1 in the
      epidermotropic stages suggests that the role of Fli-1 in MF is related to
      neoplasia and not epidermotropism.

PMID- 16965341
TI  - Diffuse dermal angiomatosis.
AB  - Diffuse dermal angiomatosis (DDA) is an acquired, benign vascular proliferation
      characterized clinically by poorly circumscribed, violaceous, livedoid plaques
      with frequent ulceration. Histologically, a diffuse interstitial proliferation of
      CD31-positive endothelial cells is present within the papillary and reticular
      dermis. Endothelial atypia, atypical mitoses, and vasculitis are lacking. We
      describe a case of DDA in a 53-year-old man with peripheral vascular
      atherosclerosis that resolved following revascularization. Early correction of
      the associated ischemic peripheral vascular disease promotes resolution of this
      unusual clinicopathologic entity.

PMID- 16965342
TI  - Precursor B-cell lymphoblastic lymphoma involving the skin.
AB  - Precursor B-cell lymphoblastic lymphoma (B-LBL) is a rare neoplasm composed of
      immature lymphocytes that demonstrate lymphoblastic morphology and express
      precursor and B-cell marker. It usually affects people of younger age group and
      causes multiple nodules on the head and neck area. The neoplasm is rare in old
      age. We report a case of B-LBL occurring in a 65-year-old man. He presented with
      multiple skin nodules on the scalp, the neck and the arm for 2 months.
      Histopathologic examination demonstrated diffuse dermal and subcutaneous
      monotonous infiltrates of medium-sized lymphoid cells with starry-sky pattern.
      Immunohistochemical study showed that the lymphoid cells of infiltrate showed
      precursor B-cell type. The patient has received combination chemotherapy three
      times and is being followed-up at the outpatient clinic.

PMID- 16965343
TI  - The diagnostic concordance of actinic keratosis and squamous cell carcinoma.

PMID- 16965345
TI  - Genetic immunity and influenza pandemics.
AB  - In addition to the great number of publications focused on the leading role of
      virus mutations and reassortment in the origin of pandemic influenza, general
      opinion emphasizes the victim side of the epidemic process. Based on the analysis
      and integration of relevant ecological, epidemiological, clinical, genetic and
      experimental data, the present article is focused on the evolution of 'virus -
      victim' ecological systems resulting in the formation of innate (i.e. genetic,
      constitutional) immunity in the involved species and populations. This kind of
      immunity functions today as the greatest natural barrier to the pandemic spread
      of influenza among humans and ecologically related kinds of animals. Global
      influenza pandemics can arise when the worldwide population contains at least a
      minimum number of people susceptible to a known or mutant influenza virus.
      Special attention is paid in this article to individual tests for the presence of
      this barrier, including the implications of specific findings for public health
      policy. Such tests could be based on in vitro observation of the action of
      relevant virus strains on primary cell cultures or on their cellular or molecular
      components extracted from individuals. The resources of the Human Genome Project
      should also be utilized.

PMID- 16965346
TI  - Epidemiology of relapsing fever borreliosis in Europe.
AB  - Tick-borne relapsing fever is a bacterial infection caused by spirochetes of the
      genus Borrelia. This zoonotic disease is transmitted to humans through the bite
      of soft ticks of the genus Ornithodoros. It is responsible for recurring fever
      access associated with spirochetemia. We present here an overview of tick-borne
      relapsing fever occurring in Europe, as well as of the potential threat to
      travellers.

PMID- 16965347
TI  - Acute sporadic hepatitis E in children: diagnostic relevance of specific
      immunoglobulin M and immunoglobulin G compared with nested reverse transcriptase
      PCR.
AB  - This study was carried out to investigate the putative role played by the
      hepatitis E virus (HEV) in acute hepatic dysfunction in paediatric patients with
      acute non-A-C hepatitis. We also evaluated the diagnostic value for anti-HEV
      immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assays relative to
      nested reverse transcriptase PCR (RT-PCR) for HEV RNA detection. Sixty-four
      children with acute hepatitis were included in the study, in addition to sixteen
      healthy children with matched age and sex. All studied subjects were negative for
      IgM antibody to hepatitis A virus, hepatitis B virus surface antigen, IgM
      antibody to hepatitis B virus core antigen, antibody to hepatitis C virus, and by
      RT-PCR for HCV RNA. HEV RNA was detected in 23.4% of patients, followed by
      detection of specific IgM in 17.2% and IgG in 12.5% of patients. Two cases were
      positive for IgG in the control group (12.5%). The sensitivity, specificity and
      accuracy were 26.7%, 85.7%, 71.9%, respectively, for IgM, and 26.7%, 91.8%, and
      76.6%, respectively, for IgG. From this study we can conclude that HEV is a
      frequent virus found sporadically with acute hepatitis among paediatric patients.
      We cannot depend upon serology alone for diagnosis; rather, both molecular and
      serological methods must be applied for accurate diagnosis.

PMID- 16965348
TI  - Presence of specific antibiotic (tet) resistance genes in infant faecal
      microbiota.
AB  - The widespread use of antibiotics for medical and veterinary purposes has led to
      an increase of microbial resistance. The antibiotic resistance of pathogenic
      bacteria has been studied extensively. However, antibiotics are not only
      selective for pathogens: they also affect all members of the gut microbiota.
      These microorganisms may constitute a reservoir of genes carrying resistance to
      specific antibiotics. This study was designed to characterize the gut microbiota
      with regard to the presence of genes encoding tetracycline resistance proteins
      (tet) in the gut of healthy exclusively breast-fed infants and their mothers. For
      this purpose we determined the prevalence of genes encoding ribosomal protection
      proteins (tet M, tet W, tet O, tet S, tet T and tet B) by PCR and characterized
      the gut microbiota by FISH in stools of infants and their mothers. The gene tet M
      was found in all the breast-fed infants and their mothers. tet O was found in all
      of the mothers' samples, whilst only 35% of the infants harboured this gene. tet
      W was less frequently found (85% of the mothers and 13% of the infants). None of
      the other genes analysed was found in any sample. Our results suggest that genes
      carrying antibiotic resistance are common in the environment, as even healthy
      breast-fed infants with no direct or indirect previous exposure to antibiotics
      harbour these genes.

PMID- 16965349
TI  - Cardiovascular risk factors in chronic Chagas' disease are associated with a
      different profile of putative heart-pathogenic antibodies.
AB  - Given that cardiovascular risk factors (CRF), such as smoking, alcoholism and
      hypertension, may contribute to the development of heart lesions, chronically
      Trypanosoma cruzi-infected individuals were studied to explore the relationship
      between the presence of such CRF, cardiomyopathy and antibodies that have been
      proposed to play a pathogenetic role in Chagas' disease. The targets of these
      antibodies were T. cruzi antigens such as cruzipain (Cz), a P ribosomal antigen
      (P2), and a component of myelin sheaths also present in T. cruzi (sulphatide).
      Individuals were classified into four groups on the basis of specific serology
      and presence of CRF: subjects with T. cruzi infection and CRF; those with
      positive serology and no CRF; seronegatives with CRF; and seronegatives without
      CRF, were analysed. Seronegatives or seropositives with CRF showed a greater
      occurrence of heart involvement (chest X-ray and/or electrocardiogram
      abnormalities). Seropositives with CRF displayed significantly higher levels of
      antisulphatide antibodies than the three remaining groups and higher levels of
      antibodies against Cz and P2 compared to the seropositives without CRF. Increased
      amounts of anti-P2 and antisulphatide antibodies were also found in seropositives
      with marked heart involvement. The presence of CRF is associated with a different
      profile of antibody responses and degree of cardiac effects.

PMID- 16965350
TI  - Development and evaluation of a rapid multianalyte particle-based flow cytometric
      assay for the quantification of meningococcal serogroup B-specific IgM antibodies
      in sera for nonculture case confirmation.
AB  - Serogroup-specific antibody has been shown to be present in the sera of patients
      recovering from meningococcal disease, and thus the detection of such antibodies
      may aid in the confirmation of disease. There are currently no standard methods
      for measuring meningococcal serogroup B-specific antibody in sera. Here, we
      report the development of a microsphere-based immunoassay which utilizes
      colominic acid from Escherichia coli 07:K1 (L):NM to detect immunoglobulin M
      directed against serogroup B polysaccharide. The serogroup B assay was
      incorporated into a multiplex assay which also detects serogroup-specific
      immunoglobulin M for meningococcal serogroups A, C, Y and W-135. Using the method
      of cross-standardization, serogroup B-specific immunoglobulin M concentrations
      were assigned to the standard serum CDC 1992. The assay is able to detect
      increases in specific immunoglobulin M concentrations from acute to convalescent
      phase serum from serogroup B cases, and can be utilized in conjunction with the
      previously developed tetraplex immunoglobulin G detection assay for serogroups A,
      C, Y and W-135.

PMID- 16965351
TI  - The diacylated lipopeptide FSL-1 induces TLR2-mediated Th2 responses.
AB  - The diacylated lipopeptide FSL-1 enhanced the generation of IgG antibodies in
      TLR2(+/+) mice, but not in TLR2(-/-) mice, when administered together with hen
      egg lysozyme as an antigen. Escherichia coli lipopolysaccharide enhanced the
      generation of antigen-specific antibodies in both TLR2(-/-) and TLR2(+/+) mice.
      In TLR2(+/+) mice, the level of enhancement due to FSL-1 was similar to that
      caused by lipopolysaccharide. Analysis of the IgG antibodies subclass
      demonstrated that the level of Th2-type IgG1 antibodies was higher than that of
      Th1-type IgG2a antibodies. Both FSL-1 and lipopolysaccharide induced production
      of IL-10 and IL-6 by splenocytes from TLR2(+/+) mice. Lipopolysaccharide also
      induced production of these cytokines by splenocytes from TLR2(-/-) mice, but FSL
      1 did not. Neither FSL-1 nor lipopolysaccharide induced IL-12p70 production by
      splenocytes from either type of mice. FSL-1 upregulated B7.2 expression in
      B220(+) cells from TLR2(+/+) mice but not those from TLR2(-/-) mice, whereas
      lipopolysaccharide upregulated B7.2 expression in B220(+) cells from both types
      of mice. FSL-1 and, to a lesser extent, lipopolysaccharide activated mitogen
      activated protein kinases in splenocytes. FSL-1 and, to a lesser extent,
      lipopolysaccharide induced the expression of c-Fos, which is known to be involved
      in Th2-type responses, in splenocytes. Thus, this study demonstrated that FSL-1
      possessed TLR2-mediated Th2-type responses in vivo.

PMID- 16965352
TI  - The in vitro effect of hydrogen peroxide on vaginal microbial communities.
AB  - This study presents a series of experiments carried out in order to elucidate the
      role of H2O2 in antimicrobial activity of lactobacilli. Vaginal swabs were
      collected from 60 premenopausal women and checked for pH and Nugent score, and
      Lactobacillus species were cultured, phenotyped and genotyped. The main outcome
      measures involved: (1) species of vaginal lactobacilli most effective in
      liberating H2O2, (2) minimal microbicidal concentrations of added H2O2, (3)
      kinetics of H2O2 liberation in relation to oxygen tension, (4) antimicrobial
      activity of pure H2O2 versus one produced by selected vaginal lactobacilli and
      the total activity of their culture supernatants. Results showed that H2O2 was
      liberated especially by: Lactobacillus delbrueckii, Lactobacillus acidophilus,
      Lactobacillus crispatus, Lactobacillus johnsonii and L. gasseri. Hydrogen
      peroxide reached concentrations from 0.05 to 1.0 mM, which under intensive
      aeration increased even up to 1.8 mM. Microorganisms related to vaginal
      pathologies show varied resistance to the action of pure H2O2. Most potent
      inhibitory activity against bacteria and yeasts was presented by Lactobacillus
      culture supernate producing H2O2, followed by the nonproducing strain and pure
      H2O2. To conclude - the antimicrobial activity of lactobacilli is a summation of
      various inhibitory mechanisms in which H2O2 plays some but not a crucial role, in
      addition to other substances.

PMID- 16965353
TI  - Characterization of a unique borreliacidal epitope on the outer surface protein C
      of Borrelia burgdorferi.
AB  - The outer surface protein C (OspC) of the Lyme disease agent, Borrelia
      burgdorferi, is an immunoprotective antigen in laboratory models of infection.
      However, to understand its protective effects, it is important to identify the
      key epitopes of this protein. We produced a borreliacidal anti-OspC monoclonal
      antibody specific to the B31 strain and identified its binding site. The
      specificity of MAb 16.22 was determined by Western blot reactivity using OspC
      derived from different Borrelia isolates which had varying amino acid sequences.
      Comparison of the OspC sequences and binding data suggested that MAb 16.22 binds
      to amino acids 133-147 of the OspC protein. To test this hypothesis, we
      synthesized a 15-amino acid peptide containing the target sequence and, using
      competition enzyme-linked immunosorbent assay (ELISA), we found that this peptide
      included the epitope of MAb 16.22. In addition, we determined that MAb 16.22 is
      able to kill of B. burgdorferi in a complement-independent fashion.

PMID- 16965354
TI  - Selection and identification of anaerobic lactobacilli producing inhibitory
      compounds against vaginal pathogens.
AB  - Two strains of Lactobacillus crispatus (15L08 and 21L07) and one strain of
      Lactobacillus jensenii (5L08) were selected from amongst 100 isolates from the
      vaginas of healthy premenopausal women for properties relevant to mucosal
      colonization and the production of H2O2 and/or bacteriocin-like compound. All
      three strains self-aggregated and adhered to vaginal epithelial cells, displacing
      well-known vaginal pathogens, such as Gardnerella vaginalis and Candida albicans.
      Lactobacillus crispatus 15L08 was characterized as a potential H2O2 producer. A
      high level of bacteriocin-like compound was synthesized by L. jensenii 5L08, with
      a bactericidal mode of action for G. vaginalis, C. albicans and Escherichia coli.
      However, H2O2-dependent activity alone was not sufficient to inhibit the growth
      of C. albicans. Simultaneous actions of H2O2 and bacteriocin-like compound
      produced by lactobacilli may be important for antagonizing pathogenic bacteria.
      These strains of lactobacilli may be excellent candidates for eventual use as
      probiotics to restore the normal microbial communities in the vaginal ecosystem.

PMID- 16965355
TI  - Implications of previous subclinical dengue infection but not virus load in
      dengue hemorrhagic fever.
AB  - In a study comparing the virus load and immune reaction between patients with
      primary and secondary dengue-2 (DEN-2) infections in a hospital-based analysis,
      we found that 40.7% (55/135) of the 135 patients had secondary DEN-2 infection
      following a DEN-2 outbreak in southern Taiwan. Most of the secondary infections
      had subclinical primary dengue infections (78.2%; 43/55). Patients with secondary
      DEN-2 infections had lower platelet counts, and blood interferon-alpha and virus
      load, but significantly higher interleukin-10 (P=0.030) and anti-DEN-1
      neutralization titers (P=0.013) than those with primary infection. Patients with
      secondary DEN-2 infection also had a higher rate of dengue hemorrhagic fever
      (DHF) (61.7% vs. 36.3%). A previous subclinical dengue infection is involved in
      the secondary DEN-2 infection associated with altered immune reaction and higher
      DHF rate, but lower blood virus load.

PMID- 16965356
TI  - Interaction of TaqI polymorphism at exon 9 of the vitamin D receptor gene with
      the negative lepromin response may favor the occurrence of leprosy.
AB  - Controversies over the vitamin D receptor (VDR) acting as a susceptibility factor
      in Mycobacterium sp. infections may be the result of incorrect population
      stratification. The risk of leprosy occurrence conditioned by VDR polymorphism
      was investigated by stratifying the population of a highly endemic Brazilian
      region into negative and positive Mitsuda responses. Leprosy patients (102) and a
      group of healthy nonconsanguineous household contacts (68) were genotyped for the
      VDR TaqI polymorphism (T/t). TT and Tt genotypes were not considered to be risk
      factors as their odds ratios (OR) were not different from those presented by the
      negative Mitsuda response individuals. The combination of the tt genotype and the
      negative Mitsuda test provided an occurrence rate 13 times higher in leprosy
      patients than in controls with positive Mitsuda responses. This suggests that
      there is a higher risk of leprosy development when individuals carry this
      unfavorable combination, and demonstrates a possible synergistic role of these
      two variables in leprosy susceptibility via effects on cellular immunity.

PMID- 16965357
TI  - Response of nitric oxide production to CpG oligodeoxynucleotides in turkey and
      chicken peripheral blood monocytes.
AB  - We evaluated the innate immune response to various synthetic CpG-containing
      oligodeoxynucleotides (CpG ODNs) by measuring nitric oxide production in the
      peripheral blood monocytes from turkey poults. The results indicate that the
      presence of the CpG dinucleotide in ODNs was a prerequisite for activation of
      turkey monocytes and induction of nitric oxide (NO) synthesis. CpG motifs and
      sequence structure of the ODNs were also found to influence stimulatory activity
      greatly. The most potent CpG ODN to induce NO synthesis in turkey monocytes was
      human-specific CpG ODN M362, followed by CpG ODN 2006 (human), CpG ODN#17
      (chicken) and CpG ODN 1826 (mouse). The optimal CpG motif for NO induction was
      GTCGTT. Phosphorothioate modification of CpG ODNs also significantly increased
      stimulatory activity. Compared with chicken monocytes, turkey monocytes appeared
      to be less sensitive to CpG motif variation, whereas chicken monocytes were found
      to respond more strictly to human-specific CpG ODNs or ODNs that contain GTCGTT
      motifs.

PMID- 16965358
TI  - Immunobiological activities of a new nontoxic lipopolysaccharide from
      Acidiphilium GS18h/ATCC55963, a soil isolate from an Indian copper mine.
AB  - A novel nontoxic lipopolysaccharide (LPS) was purified from Acidiphilium strain
      GS18h/ATCC55963. The chemical composition of the lipid A part of this LPS is
      distinctly different from that of known lipid A molecules. The LPS was
      investigated to determine its capacity to provide protection against toxic LPS or
      endotoxic shock, as has been reported for other nontoxic LPSs (Rhodobacter
      sphaeroides and Rhodobacter capsulatus), and also the extent and type of
      immunomodulatory response in terms of tumor necrosis factor alpha (TNF-alpha),
      interleukin-1beta (IL-beta), and IL-6 release as well as NO secretion by
      stimulated monocyte-macrophage systems. This study demonstrates clearly that mice
      immunized or primed with this LPS are fully protected against challenge with
      toxic Escherichia coli LPS. Unlike most of the extensively studied nontoxic LPSs,
      this LPS induced reactive nitrogen intermediates and released TNF-alpha, IL-beta
      and IL-6 in both mouse and human monocyte-macrophage systems. However, the extent
      of the cytokine and lymphokine releasing response was well below the range of the
      toxic LPS, for example that of E. coli. Owing to its capacity to provide
      immunostimulation of the host without causing any lethality to ensure protection
      against endotoxic shock, this LPS appears to have potential therapeutic value.

PMID- 16965359
TI  - Systemic and mucosal immunity to respiratory syncytial virus induced by
      recombinant Streptococcus gordonii surface-displaying a domain of viral
      glycoprotein G.
AB  - A conserved fragment comprising amino acid residues 130-230 of the G glycoprotein
      of human respiratory syncytial virus subtype A was expressed in the commensal
      bacterium Streptococcus gordonii. Recombinant streptococci displaying the G
      domain at the cell surface were used to immunize mice via both parenteral and
      mucosal routes. Subcutaneous immunization induced respiratory syncytial virus
      specific serum immunoglobin G (IgG) capable of partially controlling virus
      replication in the lungs. Intranasal immunization with live bacteria stimulated
      the production of IgA against both the whole virus and the G domain in serum and
      bronchoalveolar fluid. Upon challenge, immunized animals had significantly lower
      virus titres in the lungs than the controls. Our results show for the first time
      that the G domain-expressing S. gordonii strain elicits both systemic and mucosal
      immunity that reduced respiratory syncytial virus replication in the lungs of
      mice.

PMID- 16965360
TI  - Production and release of heat-labile toxin by wild-type human-derived
      enterotoxigenic Escherichia coli.
AB  - Production and release of heat-labile toxin (LT) by wild-type enterotoxigenic
      Escherichia coli (ETEC) strains, isolated from diarrheic and asymptomatic
      Brazilian children, was studied under in vitro and in vivo conditions. Based on a
      set of 26 genetically diverse LT(+) enterotoxigenic E. coli strains, cell-bound
      LT concentrations varied from 49.8 to 2415 ng mL(-1). The amounts of toxin
      released in culture supernatants ranged from 0% to 50% of the total synthesized
      toxin. The amount of LT associated with secreted membrane vesicles represented
      <5% of the total toxin detected in culture supernatants. ETEC strains secreting
      higher amounts of LT, but not those producing high intracellular levels of cell
      bound toxin, elicited enhanced fluid accumulation in tied rabbit ileal loops,
      suggesting that the strain-specific differences in production and secretion of LT
      correlates with symptoms induced in vivo. However, no clear correlation was
      established between the ability to produce and secrete LT and the clinical
      symptoms of the infected individuals. The present results indicate that
      production and release of LT by wild-type human-derived ETEC strains are
      heterogeneous traits under both in vitro and in vivo growth conditions and may
      impact the clinical outcomes of infected individuals.

PMID- 16965361
TI  - Mycobacterial codon optimization of the gene encoding the Sm14 antigen of
      Schistosoma mansoni in recombinant Mycobacterium bovis Bacille Calmette-Guerin
      enhances protein expression but not protection against cercarial challenge in
      mice.
AB  - A mycobacterial codon-optimized gene encoding the Sm14 antigen of Schistosoma
      mansoni was generated using oligonucleotide assembly. This synthetic gene
      enhanced approximately fourfold the protein expression level in recombinant
      Mycobacterium bovis Bacille Calmette-Guerin (rBCG) when compared to that obtained
      using the native gene in the same expression vector. Immunization of mice with
      rBCG expressing Sm14 via the synthetic gene induced specific cellular Th1
      predominant immune responses, as determined by interferon-gamma production of
      Sm14-stimulated splenocytes, which were comparable to those recorded in animals
      immunized with an rBCG strain expressing the native gene. Administration of a
      single dose of the rBCG-Sm14 construct carrying the synthetic gene conferred
      protection against cercarial challenge in outbred Swiss mice, at a level
      equivalent to those provided by either a single dose of rBCG expressing the
      native gene or three doses of Escherichia coli-derived recombinant Sm14. Our data
      demonstrated that despite improving the level of antigen expression, the codon
      optimization strategy did not result in enhanced immunity or protection against
      cercarial S. mansoni challenge.

PMID- 16965362
TI  - Adenylate cyclase influences filamentous haemagglutinin-mediated attachment of
      Bordetella pertussis to epithelial alveolar cells.
AB  - Attachment to epithelial cells in the respiratory tract is a key event in
      Bordetella pertussis colonization. Filamentous haemagglutinin (FHA) is an
      important virulence factor mediating adhesion to host cells. In this study, the
      relevance of the interaction between FHA and adenylate cyclase toxin (ACT) during
      bacterial attachment was investigated. Mutants lacking either FHA or ACT showed
      significantly decreased adherence to epithelial respiratory cells. The use of
      several ACT-specific monoclonal antibodies and antiserum showed that the decrease
      in attachment of strains lacking ACT expression could not be explained by the
      adhesin-like activity of ACT, or a change of any of the biological activities of
      ACT. Immunoblot analysis showed that the lack of ACT expression did not interfere
      with FHA localization. An heparin-inhibitable carbohydrate-binding site is
      crucial in the process of FHA-mediated bacterial binding to epithelial cells. In
      the presence of heparin attachment of wild-type B. pertussis, but not of the
      isogenic ACT defective mutant, to epithelial cells was significantly decreased.
      These results suggest that ACT enhances the adhesive functions of FHA, and
      modifies the performance of the FHA heparin-inhibitable carbohydrate binding
      site. We propose that the presence of ACT in the outer membrane of B. pertussis
      to play a role in the functionality of FHA.

PMID- 16965363
TI  - A novel phenotype based on esterase electrophoretic polymorphism for the
      differentiation of Lactococcus lactis ssp. lactis and cremoris.
AB  - AIMS: To evaluate the esterase phenotype in Lactococcus lactis strains isolated
      from traditional Tunisian dairy products. METHODS AND RESULTS: A collection of 55
      L. lactis strains isolated from traditional fermented milk products and three
      reference strains were identified at species and subspecies level using molecular
      methods targeted to the 16S rRNA gene and to the histidine operon. The genotypic
      data obtained allowed the identification of the strains as L. lactis ssp. lactis
      and L. lactis ssp. cremoris with the prevalence of the ssp. lactis. The
      phenotypic identification based on arginine hydrolysis, the growth at 40 degrees
      C and in presence of 4% NaCl showed several discrepancy with the identification
      data based on genotypic analysis. Additional experiments carried out evaluating
      the esterase electrophoretic patterns revealed four classes of esterases
      identified on the basis of their electrophoretic mobility and specific activity
      on alpha- and beta-naphthyl ester of acetate and propionate. Esterase profiles
      discriminated the strains in two main groups corresponding to the subspecies
      cremoris and lactis according to a DNA-based identification. CONCLUSIONS: The
      evaluation of esterase activity represents a novel phenotype for the taxonomic
      discrimination of the L. lactis ssp. lactis and cremoris. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Besides the DNA-based techniques that allow the rapid and accurate
      species/subspecies identification, the electrophoretic esterase profiles of L.
      lactis strains represents: (i) a new phenotypic tool to understand the physiology
      and the ecology of this species; and (ii) a new test for the potential selection
      of flavour producing strains.

PMID- 16965364
TI  - Menstrum for culture preservation and medium for seed preparation in a tetanus
      toxin production process containing no animal or dairy products.
AB  - AIMS: To completely eliminate animal and dairy products from the lyophilization
      menstrum and the seed medium used to produce tetanus toxin with Clostridium
      tetani. METHODS AND RESULTS: Tetanus toxin production in a recently developed
      fermentation medium lacking animal and dairy products was studied with different
      seed media. It was found that soy peptone could completely replace the beef heart
      infusion plus animal peptone previously used as seed medium. In addition, we
      found that cells lyophilized in soy milk could replace the usual type of cells
      lyophilized in cow's milk. CONCLUSIONS: We have now developed a complete tetanus
      toxin production process containing no animal and dairy products. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Toxoid preparations made from toxin produced with animal
      and dairy products can contain undesirable contaminants such as the prion causing
      bovine spongiform encephalopathy (Mad Cow's Disease) or antigenic peptides that
      stimulate anaphylactic reactions and other undesirable immune reactions in
      immunized hosts. The new vegetable-based process described here avoids such
      unfortunate possibilities.

PMID- 16965365
TI  - Immunomagnetic recovery of Mycobacterium bovis from naturally infected
      environmental samples.
AB  - AIMS: To adapt an immunomagnetic capture (IMC) technique to concentrate and
      cultivate Mycobacterium bovis from environmental samples including soil, faeces
      and urine. METHODS AND RESULTS: Cells of Myco. bovis BCG and wild-type Myco.
      bovis were successfully isolated and cultured from seeded and naturally infected
      materials respectively. The IMC cell recovery estimated by colony forming units
      (CFUs) counts ranged from 0.10% to 0.16% for spiked media, and 0.15-0.36% for
      naturally infected soil and faeces. Recovery estimated by cell counts calculated
      using semi-quantitative PCR ranged from 80.3% to 88.6% for spiked and 84.1-88.2%
      for naturally infected material. The differences in the recovery rates estimated
      by CFUs compared with pixel intensity is likely to be due to clustering of cells
      on culture plates, thereby underestimating the true cell count. CONCLUSIONS: The
      IMC techniques can be applied to isolate viable wild type Myco. bovis from
      naturally contaminated environmental samples. SIGNIFICANCE AND IMPACT OF STUDY:
      Cultivation of Myco. bovis from environmental samples using traditional methods
      is extremely problematic. Here, we demonstrate a novel development of IMC
      techniques that will greatly facilitate the study of the organism in situ in
      order to assess its epidemiological importance in bovine tuberculosis
      persistence.

PMID- 16965366
TI  - Improvement of maltotriose fermentation by Saccharomyces cerevisiae.
AB  - AIMS: To enhance the fermentation of maltotriose by industrial Saccharomyces
      cerevisiae strains. METHODS AND RESULTS: The capability to ferment maltotriose by
      an industrial yeast strain that uses this sugar aerobically was tested in shake
      flasks containing rich medium. While the presence of maltose in the medium did
      not improve maltotriose fermentation, enhanced and constitutive expression of the
      AGT1 permease not only increased the uptake of maltotriose, but allowed efficient
      maltotriose fermentation by this strain. Supplementation of the growth medium
      with 20 mmol magnesium l(-1) also increased maltotriose fermentation.
      CONCLUSIONS: Over expression of the AGT1 permease and magnesium supplementation
      improved maltotriose fermentation by an industrial yeast strain that respired but
      did not ferment this sugar. SIGNIFICANCE AND IMPACT OF THE STUDY: This work
      contributes to the elucidation of the roles of the AGT1 permease and nutrients in
      the fermentation of all sugars present in starch hydrolysates, a highly desirable
      trait for several industrial yeasts.

PMID- 16965367
TI  - Production of poly-beta-hydroxyalkanoates from soy molasses oligosaccharides by
      new, rapidly growing Bacillus species.
AB  - AIMS: To isolate and characterize bacteria from nature capable of producing poly
      beta-hydroxyalkanoates in high yields from soy molasses oligosaccharides. METHODS
      AND RESULTS: Several strains of bacteria were obtained from enrichment cultures
      employing raffinose as major carbon source and inoculated with soybean field
      soil, lake sediment, or lake water. Many of the isolates were Bacillus species
      and produced polyhydroxyalkanoates (PHAs) to high yield. The raffinose-degrading
      isolates produced endospores, were highly saccharolytic, and both respired and
      fermented a variety of mono-, di-, tri- and tetrasaccharides. Strain CL1 produced
      90% of cell dry mass as PHA from various sugars, including raffinose, and did so
      without requiring a nutrient limitation. CONCLUSIONS: Strain CL1 could be the
      catalyst for an industrial fermentation converting soy molasses and other waste
      carbohydrates to PHAs. The properties of this organism that make it ideally
      suited for such a fermentation include (i) its ability to use a wide variety of
      plant-associated carbohydrates as PHA feedstocks; (ii) its rapid growth; (iii)
      its ability to grow under anoxic conditions; and (iv) its ability to produce
      spores. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of
      bacteria capable of making biodegradable plastics to high yield from soy molasses
      oligosaccharides.

PMID- 16965368
TI  - Optimization of culture conditions for the production of haloalkaliphilic
      thermostable protease from an extremely halophilic archaeon Halogeometricum sp.
      TSS101.
AB  - AIMS: Isolation and screening of extreme halophilic archaeon producing
      extracellular haloalkaliphilic protease and optimization of culture conditions
      for its maximum production. METHODS AND RESULTS: Halogeometricum sp. TSS101 was
      isolated from salt samples and screened for the secretion of protease on gelatin
      and casein plates containing 20% NaCl. The archaeon was grown aerobically in a
      250 ml flask containing 50 ml of (w/v) NaCl 20%; MgCl(2) 1%; KCl 0.5%; trisodium
      citrate 0.3%; and peptone 1%; pH 7.2 at 40 degrees C on rotary shaker. The
      production of enzyme was investigated at various pH, temperatures, NaCl
      concentrations, metal ions and different carbon and nitrogen sources. The
      partially purified protease had activity in a broad pH range (7.0-10.0) with
      optimum activity at pH 10.0 and a temperature (60 degrees C). The enzyme was
      thermostable and retained 70% initial activity at 80 degrees C. Maximum protease
      production occurred at 40 degrees C in a medium containing 20% NaCl (w/v) and 1%
      skim milk powder after 84 h in shaking culture. Enzyme secretion was observed at
      a broad pH range of 7.0-10.0. Addition of CaCl(2) (200 mmol) to the culture
      medium enhanced the production of protease. Protein rich flours proved to be
      cheap and good alternative source for enzyme production. Different osmolytes were
      tested for the growth and production of haloalkaliphilc protease and found that
      betaine and glycerol enhanced growth without secretion of the protease.
      Immobilization studies showed that whole cells immobilized in 2% alginate beads
      were stable up to 10 batches and able to secrete the protease, which attained
      maximum production within 60 h under shaking conditions. CONCLUSIONS:
      Halogeometricum sp. TSS101 secreted an extracellular haloalkaliphilic and
      thermostable protease. The optimum conditions required for maximum production are
      20% NaCl, 1% skim milk powder and temperature at 40 degrees C. Addition of
      CaCl(2) (200 mmol) enhanced the enzyme production. Immobilization of whole cells
      in absence of NaCl proved to be useful for continuous production of
      haloalkaliphilic protease. SIGNIFICANCE AND IMPACT OF THE STUDY: The low cost
      protein rich flours were used as an alternative carbon and nitrogen sources for
      enzyme production. Immobilization of halophilic cells in alginate beads can be
      used in continuous production of halophilic enzyme. The halophilic and
      thermostable protease from Halogeometricum sp. TSS101 is good source for
      industrial applications and can be a suitable source for preparation of fish
      sauce.

PMID- 16965369
TI  - Susceptibility of Escherichia coli to L-selenaproline and other L-proline
      analogues in laboratory culture media and normal human urine.
AB  - AIMS: The aims of this study were to identify analogues of L-proline which
      inhibit the growth of Escherichia coli in both laboratory culture media and
      normal human urine and to study their mechanisms of uptake. METHODS AND RESULTS:
      The susceptibility of E. coli to L-proline analogues was studied by radial streak
      assays on agar plates and by minimal inhibitory concentration determinations in
      liquid media. Only L-selenaproline (SCA) inhibited growth in Mueller-Hinton
      medium and human urine as well as in glucose minimal medium. L-Proline did not
      prevent the inhibition of growth by SCA and strains defective in L-proline
      transport were as susceptible to SCA as wild-type strains. However, E. coli was
      resistant to SCA in the presence of L-cysteine and L-cystine. Spontaneous mutants
      selected for resistance to SCA or L-selenocystine were resistant to the other
      compound and had reduced growth in minimal medium containing L-cysteine or L
      cystine as the sole sulfur source. CONCLUSIONS: L-selenaproline inhibited the
      growth of E. coli under conditions that may occur in the urinary tract and
      appeared to be taken up by the L-cystine transport system. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Although urinary tract infections caused by E. coli can be
      treated with sulfamethoxazole/trimethoprim and quinolones, resistance to these
      antibiotics has been increasing. These results suggest that L-selenaproline may
      represent a new class of compounds that could be used to treat these infections.

PMID- 16965370
TI  - Detection of human enteric viruses in shellfish collected in Tunisia.
AB  - AIMS: The aim of this study was to detect the main pathogenic human RNA enteric
      viruses able to persist in the environment such as astrovirus, enterovirus,
      norovirus and hepatitis A virus (HAV) in shellfish collected from two locations
      in northern Tunisia. METHODS AND RESULTS: Viruses were eluted from digestive
      tissues and concentrated by polyethylene glycol precipitation before nucleic acid
      extraction and purification. After checking for inhibitors, all viruses were
      detected by reverse transcription-polymerase chain reaction (RT-PCR) and
      confirmed by hybridization. Overall, 83% of the samples were found positive for
      at least one virus. Astrovirus was detected in 61% of the samples, norovirus in
      35% and HAV in 26%. Surprisingly, only one sample was found positive for
      enterovirus. CONCLUSIONS: The mean number of positive samples found in this study
      is in accordance with the data found in the literature, indicating that no real
      difference exists in this respect among countries studied. A notable exception is
      HAV, which reflects the epidemiological status of the population. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This study highlights the interest to analyse shellfish
      samples from different production areas. These data will be helpful to understand
      virus circulation and to improve shellfish safety. The results, which confirm
      contamination, necessitate the development of appropriate studies and monitoring
      in all shellfish-producing countries.

PMID- 16965371
TI  - Occurrence, virulence characteristics and antimicrobial resistance of Escherichia
      coli O157 in slaughtered cattle and diarrhoeic calves in West Bengal, India.
AB  - AIMS: (i) To study the occurrence of Escherichia coli serotype O157 in cattle
      stool in West Bengal, India, and (ii) the virulence properties and antimicrobial
      resistance of the E. coli isolates. METHODS AND RESULTS: Following enrichment in
      modified EC broth and plating onto HiCrome MS.O157 agar, a total of 14 strains of
      E. coli serotype O157 was isolated from faecal samples from two (2.04%)
      slaughtered cattle and six (7.59%) diarrhoeic calves. By multiplex PCR, Shiga
      toxin genes were detected in all the isolates. The enterohaemolysin phenotype was
      found in all, but one strain. Among 14 strains, ten were resistant to at least
      one of the antimicrobial agents tested. Multiple antibiotic resistance was
      frequent. CONCLUSIONS: The study showed that occurrence of Shiga toxin-producing
      and multiple antibiotic-resistant E. coli O157 among cattle population in this
      region of India is significant. SIGNIFICANCE AND IMPACT OF THE STUDY: Considering
      routine human contacts with cattle, a large human population in this region may
      be at risk for exposure to Shiga toxin-producing E. coli O157.

PMID- 16965372
TI  - Marine sponge Craniella austrialiensis-associated bacterial diversity revelation
      based on 16S rDNA library and biologically active Actinomycetes screening,
      phylogenetic analysis.
AB  - AIMS: The aim of this study was to investigate the bacterial diversity associated
      with the sponge Craniella australiensis using a molecular strategy and isolating
      Actinomycetes with antimicrobial potentials. METHODS AND RESULTS: The bacterial
      diversity associated with South China Sea sponge C. austrialiensis was assessed
      using a 16S rDNA clone library alongside restriction fragment length polymorphism
      and phylogenetic analysis. It was found that the C. austrialiensis-associated
      bacterial community consisted of alpha, beta and gamma-Proteobacteria,
      Firmicutes, Bacteroidetes as well as Actinobacterium. Actinomycetes were isolated
      successfully using seawater medium with sponge extracts. According to the BLAST
      and phylogenetic analysis based on about 600-bp 16S rDNA sequences, 11 of the
      representative 23 isolates closely matched the Streptomyces sp. while the
      remaining 12 matched the Actinomycetales. Twenty Actinomycetes have antimicrobial
      potentials, of which 15 are found to possess broad-spectrum antimicrobial
      potentials. CONCLUSIONS: The sponge C. austrialiensis-associated bacterial
      community is very abundant including Proteobacteria, Firmicutes, Bacteroidetes
      and Actinobacterium while Actinomycetes is not predominant. Artificial seawater
      medium with sponge extracts is suitable for Actinomycetes isolation. Most of the
      isolated C. austrialiensis-associated Actinomycetes have a broad spectrum of
      antimicrobial activity. SIGNIFICANCE AND IMPACT OF THE STUDY: This study revealed
      the diversity of the bacterial community and the isolated Actinomycetes with
      antimicrobial potentials associated with sponge C. australiensis.

PMID- 16965373
TI  - Cooperative biodegradation of geosmin by a consortium comprising three gram
      negative bacteria isolated from the biofilm of a sand filter column.
AB  - AIMS: To isolate and identify bacteria from a sand filter column capable of
      degrading the taste and odour compound, geosmin. In doing so, to investigate if
      these organisms degrade geosmin either individually or if an alternative
      mechanism is utilized. METHODS AND RESULTS: Geosmin-degrading bacteria from a
      biologically active sand filter column were enriched by their growth in a minimal
      medium supplemented with geosmin as the sole carbon source. By day 51, 21.7 mg l(
      1) of geosmin had been degraded as determined by solid-phase microextraction gas
      chromatography/mass spectrometry, and was accompanied by a 2.12 log(10) increase
      in active bacterial numbers as measured using the BacLight(TM) bacterial
      viability kit and flow cytometric enumeration. During the onset of geosmin
      degradation, the predominance of three bacteria, most similar to previously
      cultured species of Sphingopyxis alaskensis, Novosphingobium stygiae and
      Pseudomonas veronii based on 16S rRNA gene sequences was detected by denaturing
      gradient gel electrophoresis. Subsequent isolation of these organisms revealed
      that degradation of geosmin, when present as either the sole carbon source
      (ranging from 40 ng l(-1) to 20 mg l(-1)) or when spiked into sterile reservoir
      water (37 and 131 ng l(-1)), occurred only when all three isolates were present.
      None of the isolates was shown to be capable of degrading geosmin either
      individually or in any combination of two. CONCLUSIONS: This study has reported,
      for the first time, the cooperative degradation of geosmin by a consortium
      comprising three gram-negative bacteria isolated from a biologically active sand
      filter column. SIGNIFICANCE AND IMPACT OF THE STUDY: These results are important
      for researchers currently employing molecular-based approaches to further
      understand the biodegradation of geosmin by bacteria, as such studies may be
      complicated by the discovery of geosmin degradation occurring by a consortium.
      This study also advances the knowledge surrounding the types of bacteria capable
      of degrading the taste and odour compound, as investigations to date regarding
      this are limited.

PMID- 16965374
TI  - [Pasteurella] caballi infection not limited to horses - a closer look at taxon 42
      of Bisgaard.
AB  - AIM: To investigate if taxon 42 of Bisgaard isolated from pigs represents genuine
      [Pasteurella] caballi, which was previously only isolated from horses. METHODS
      AND RESULTS: A total of 15 field isolates from horses and pigs from five
      different countries representing three continents were subjected to extended
      phenotypical characterization. Although minor differences were observed between
      taxon 42 and [P.] caballi, these differences did not allow phenotypic separation.
      Ribotyping based on HindIII digestion showed five profiles based on nine band
      positions. One [P.] caballi strain and two taxon 42 strains shared the same
      profile. Ribotyping using HpaII gave a higher diversity with nine profiles based
      on ten band positions. While no profiles were shared between the taxon 42 and
      [P.] caballi strains, pattern analysis showed that two of the taxon 42 isolates
      were most similar (91% similarity) with a [P.] caballi isolate. The 16S rRNA gene
      sequencing of one strain of taxon 42 and one strain of [P.] caballi was performed
      and compared with the published sequence for the type strain of [P.] caballi. The
      three strains showed nearly identical sequences with at least 99.8% similarity.
      DNA re-associations measured by the micro-well method were 79 and 77%,
      respectively between the type strain of [P.] caballi and two strains of taxon 42
      representing distinct ribotypes and confirmed that taxon 42 belongs to [P.]
      caballi. CONCLUSION: The present investigation documents that [P.] caballi can be
      isolated from clinical respiratory specimens from pigs and the recognized
      association with respiratory infections in horses and horse bite infection in
      humans. Strains classified as taxon 42 are [P.] caballi isolated from pigs and
      for both pigs and horses, lesions mainly include the respiratory tract.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The results will improve the diagnostics
      and progress studies of virulence and epidemiology of [P.] caballi.

PMID- 16965375
TI  - A novel NADP+-dependent L-1-amino-2-propanol dehydrogenase from Rhodococcus
      erythropolis MAK154: a promising enzyme for the production of double chiral
      aminoalcohols.
AB  - AIM: A novel NADP(+)-dependent L-1-amino-2-propanol dehydrogenase was isolated
      from Rhodococcus erythropolis MAK154, and characterized. METHODS AND RESULTS: The
      enzyme was inducibly produced on cultivation with aminoalcohols such as 1-amino-2
      propanol, 1-amino-2-butanol and 2-aminocyclohexanol. The enzyme catalyses the
      NADP(+)-dependent oxidation of several aminoalcohols, and also the NADPH
      dependent asymmetric reduction of an aminoketone compound to a double chiral
      aminoalcohol, d-pseudoephedrine. Amino acid sequence analysis showed that the
      enzyme might belong to the short-chain dehydrogenase/reductase family.
      CONCLUSIONS: NADP(+)-dependent L-1-amino-2-propanol dehydrogenase isolated from
      R. erythropolis MAK154 reversibly catalysed dehydrogenation of aminoalcohols, and
      exhibited a unique sterospecifity for the reduction reaction. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The enzyme is a promising catalyst for the production of
      double chiral compound, d-pseudoephedrine, from prochiral substrate.

PMID- 16965376
TI  - Development of monoclonal antibodies for simple identification of Vibrio
      alginolyticus.
AB  - AIMS: The present study was aimed to produce monoclonal antibodies (MAbs) for
      simple and specific identification of Vibrio alginolyticus infection in shrimp.
      METHODS AND RESULTS: Mice were immunized with heat killed V. alginolyticus four
      times at 2-week intervals. The best response mouse was used for spleen donor in
      hybridoma production. Screening of hybridoma clones producing desired antibodies
      was performed by dot blotting against V. alginolyticus and other bacterial
      species, Western blotting and immunohistochemistry of infected shrimp tissues.
      Four groups of MAbs were obtained; the first group of MAbs demonstrated their
      limited specificity only to V. alginolyticus used for immunization, while the
      second and the third groups recognized all three isolates of V. alginolyticus
      used for testing. The fourth group of MAbs bound to all three isolates of V.
      alginolyticus and also recognized Vibrio parahaemolyticus, Vibrio harveyi, Vibrio
      fluvialis and Vibrio vulnificus but did not bind to Vibrio mimicus, Vibrio
      cholerae, Vibrio penaeicida and other bacterial species tested. MAbs in groups 1,
      2 and 3 were able to use for the detection of bacterial infection in the tissues
      by means of immunohistochemistry. CONCLUSIONS: MAbs specific to V. alginolyticus
      was produced. These MAbs can be used for specific identification of the bacteria
      by simple 'dot blotting' method and immunohistochemistry. SIGNIFICANCE AND IMPACT
      OF THE STUDY: This study demonstrated an immunological tool that can be used for
      simple and accurate identification of V. alginolyticus as well as for the
      diagnosis of V. alginolyticus infection in animals. This immunological tool can
      replace costly and laborious biochemical tests.

PMID- 16965377
TI  - Cytotoxic activity of clinical Stenotrophomonas maltophilia.
AB  - AIMS: To determine the potential virulence factors produced by culture
      supernatants of clinical isolates of Stenotrophomonas maltophilia. METHODS AND
      RESULTS: Culture supernatants of clinical isolates of S. maltophilia were assayed
      for haemolytic, enzymatic (lipase, protease and phospholipase) and cytotoxic
      activity. Cytotoxic activity was assayed in Vero (African green monkey), HeLa
      (human cervix) and HEp-2 (human larynx epidermoid carcinoma) cells. Microscopic
      analyses revealed intensive rounding, loss of intercellular junctions and
      membrane alterations (blebbing) followed by death of HEp-2 cells. In Vero and
      HeLa cells, the cytotoxic effects were characterized by vigorous endocytosis and
      cell aggregation. The viability of cultured mammalian cells was determined with
      neutral red and demonstrated that the sensitivity among the cells was different.
      This activity was inactivated by heating at 56 degrees C for 15 min and protease
      inhibitors did not inhibit cytotoxic activity. The clinical S. maltophilia
      presented a cell-free haemolytic activity similar to the 'hot-cold' haemolysins.
      CONCLUSIONS: S. maltophilia culture supernatants caused vigorous endocytosis and
      cell aggregation in HeLa and Vero cells, produced haemolytic and enzymatic
      activities. SIGNIFICANCE AND IMPACT OF THE STUDY: This work revealed the presence
      of putative virulence factors that could be associated with human infections
      involving Stenotrophomonas maltophilia strains.

PMID- 16965378
TI  - Comparison of two commercial methods with PCR restriction fragment length
      polymorphism of the tuf gene in the identification of coagulase-negative
      staphylococci.
AB  - AIMS: Two commercial methods for the identification of coagulase-negative
      staphylococci (CNS) were compared with the restriction fragment length
      polymorphism (RFLP) of the amplified tuf gene, which served as the reference
      method. METHODS AND RESULTS: One hundred and forty-five CNS were evaluated using
      the API 32 Staph ID and the Crystal GP/ID BBL systems. The PCR-RFLP of the tuf
      gene served as the reference method. The APIStaph and the GP/ID BBL had an
      overall rate of agreement with the molecular method of 58.6% and 46.2%
      respectively, with the inability of the GP/ID BBL to characterize 11.7% of the
      isolates. The APIStaph showed higher sensitivity and better agreement than the
      GP/ID BBL with the PCR-RFLP, except for Staphylococcus hominis and Staphylococcus
      capitis. CONCLUSIONS: Neither of the commercial systems was as reliable as the
      PCR-RFLP method for identifying isolates of CNS. Overall the APIStaph had better
      agreement with the PCR-RFLP than the GP/ID system. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The results indicate that the PCR-RFLP method is more reliable than the
      two commercial systems tested, suggesting that it is more reliable for routinely
      identifying CNS.

PMID- 16965379
TI  - The detection of environmental autoinducing peptide quorum-sensing genes from an
      uncultured Clostridium sp. in landfill leachate reactor biomass.
AB  - AIMS: To elucidate whether a dominant uncultured clostridial (Clostridium
      thermocellum-like) species in an environmental sample (landfill leachate),
      possesses an autoinducing peptide (AIP) quorum-sensing (QS) gene, although it may
      not be functional. METHODS AND RESULTS: A modified AIP accessory gene regulator
      (agr)C PCR protocol was performed on extracted DNA from a landfill leachate
      sample (also characterized by 16S rRNA gene cloning) and the PCR products were
      cloned, sequenced and phylogenetically analysed. It appeared that two agrC gene
      phylotypes existed, most closely related to the C. thermocellum agrC gene,
      differing by only 1 bp. CONCLUSIONS: It is possible to specifically identify and
      characterize the agrC AIP QS gene from uncultured Firmicutes (C. thermocellum
      like) bacteria derived from environmental (landfill leachate) sample.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first successful attempt at
      identifying AIP QS genes from a cellulolytic environment (landfill). The agrC
      gene was identified as being most closely related to the C. thermocellum agrC
      gene, the same bacterium identified as being dominant, according to 16S rRNA gene
      cloning and subsequently fluorescence in situ hybridization analyses, in the same
      biomass.

PMID- 16965380
TI  - Growth stimulatory effect of Ochrobactrum intermedium and Bacillus cereus on
      Vigna radiata plants.
AB  - AIMS: This study assessed the plant growth-promoting ability of the bacterial
      strains Ochrobactrum intermedium (isolate CrT-1) and Bacillus cereus (isolate S
      6). METHODS AND RESULTS: Two chromium resistant bacterial strains isolated from
      chromium-contaminated wastewater and soils were identified as O. intermedium CrT
      1 and B. cereus S-6. These strains were inoculated on seeds of mungbean Vigna
      radiata var NM-92, which were germinated and grown under chromate salts (300
      microg ml(-1) of CrCl(3)or K(2)CrO(4)). The data show that Cr(VI) was more toxic
      because of its better availability to plants roots when compared with Cr(III).
      The major part of Cr(VI) supplied to the seedlings was reduced to Cr(III) in the
      rhizosphere by the bacterial strains, thus lowering the toxicity of chromium to
      seedlings. CONCLUSIONS: Strains have significant Cr(VI) resistance and reduction
      potential and have ability to enhance mungbean plant growth under chromium
      stress. SIGNIFICANCE AND IMPACT OF THE STUDY: These strains could be utilized for
      the growth of economically important cash crops as well as for the bioremediation
      of chromium-polluted soils.

PMID- 16965382
TI  - Depressive symptoms in mid-pregnancy, lifetime stressors and the 5-HTTLPR
      genotype.
AB  - Few studies of gene-environment interactions for the serotonin transporter
      promoter polymorphism (5-HTTLPR), life stressors and depression have considered
      women separately or examined specific types of stressful life events. None have
      looked at depression during pregnancy. In the Pregnancy Outcomes and Community
      Health (POUCH) Study, women were queried about history of stressful life events
      and depressive symptoms at the time of enrollment (15-27 weeks gestation).
      Stressful life events were grouped a priori into "subconstructs" (e.g. economic,
      legal, abuse, loss) and evaluated by subconstruct, total subconstruct score and
      total stressful life event score. The effect of genotype on the association
      between stressful life events and elevated depressive symptoms was assessed in
      568 white non-Hispanic participants. The relationship between exposure to abuse
      and elevated depressive symptoms was more pronounced in the s/s group (OR = 24.5)
      than in the s/l group (OR = 3.0) and the l/l group (OR = 7.7), but this
      significant interaction was detected only after excluding 73 (13%) women with
      recent use of psychotropic medications. There was no evidence of gene-environment
      interaction in analytic models with other stressful life events subconstructs,
      total subconstruct score or total stressful life events score. These data offer
      modest support to other reports of gene-environment interaction and highlight the
      importance of considering specific stressful life events.

PMID- 16965383
TI  - PI3K/Akt-dependent Epo-induced signalling and target genes in human early
      erythroid progenitor cells.
AB  - Erythropoietin (Epo) is the major regulator of differentiation, proliferation and
      survival of erythroid progenitors, but the Epo-induced changes in gene expression
      that lead to these effects are not fully understood. The aim of this study was to
      examine how Epo, via activation of phosphatidylinositol 3-kinase (PI3K)/Akt,
      exerts its role in the development of erythroid progenitors from CD34+ cells, and
      to identify early Epo target genes in human erythroid progenitors. In CD34+
      progenitor cells, Epo alone was able to induce cell cycle progression as
      demonstrated by upregulation of cyclin D3, E and A leading to
      hyperphosphorylation of the retinoblastoma protein (RB). These effects were
      completely counteracted by the PI3K inhibitor LY294002. Furthermore, enforced
      expression of an activated form of Akt kinase highly augmented Epo-induced
      erythropoiesis. Fluorescent-activated cell sorting (FACS)-sorted CD34+CD71+CD45RA
      GPA- erythroid progenitors stimulated with Epo in the presence or absence of
      LY294002 were subjected to gene expression profiling. Several novel target genes
      of Epo were identified, and the majority were regulated in a PI3K-dependent
      manner, including KIT (CD117) and CDH1 (E-cadherin). FACS analysis of Epo
      stimulated erythroid progenitors showed that the increased mRNA expression of KIT
      and CDH1 was accompanied by an induction of the corresponding proteins CD117 and
      E-cadherin.

PMID- 16965384
TI  - Chromosomal locus 19p13 as potential hotspot for aberrant gene expression in
      relapsed paediatric acute lymphoblastic leukaemia.

PMID- 16965385
TI  - The MLL partial tandem duplication in acute myeloid leukaemia.
AB  - Mixed lineage leukaemia gene-partial tandem duplications (MLL-PTD) characterise
      acute myeloid leukaemia (AML) with trisomy 11 and AML with a normal karyotype.
      MLL-PTD confer a worse prognosis with shortened overall and event free survival
      in childhood and adult AML. In spite of these clinical observations, the
      leukaemogenic mechanism has, so far, not been determined. This review summarises
      clinical studies on MLL-PTD positive AML and recent experimental findings on the
      putative leukaemogenic role of MLL-PTD.

PMID- 16965386
TI  - Rituximab-induced haemorrhagic thrombocytopenia in a patient with hairy cell
      leukaemia.

PMID- 16965387
TI  - Combined chelation therapy improves glucose metabolism in patients with beta
      thalassaemia major.

PMID- 16965388
TI  - High incidence of the ETV6/RUNX1 fusion gene in paediatric precursor B-cell acute
      lymphoblastic leukaemias with trisomy 21 as the sole cytogenetic change: a Nordic
      series of cases diagnosed 1989-2005.
AB  - Trisomy 21 is common in ETV6/RUNX1-positive acute lymphoblastic leukaemia (ALL);
      both these aberrations are associated with a favourable outcome. The prognostic
      impact of +21 as a sole cytogenetic change could be due to a cryptic
      t(12;21)(p13;q22). The occurrence of ETV6/RUNX1 was determined in 66 childhood
      ALLs with an acquired +21 and a chromosome number <51. ETV6/RUNX1 was found in
      45% of cases and in the majority (10/18; 56%) of ALLs with sole +21. Event-free
      survival did not differ between the t(12;21)-positive and -negative cases. Thus,
      the prognostic impact of +21 is not attributable to cryptic ETV6/RUNX1.

PMID- 16965389
TI  - A human monoclonal antiprothrombin antibody is thrombogenic in vivo and
      upregulates expression of tissue factor and E-selectin on endothelial cells.
AB  - Prothrombin is now accepted as one of the target antigens recognised by
      antiphospholipid (aPL) antibodies. However, it is not clear whether anti
      prothrombin antibodies are pathogenic in vivo and if so, the possible
      mechanism(s) involved. Here, we examined the pathogenic effects of the IS6
      monoclonal anti-prothrombin antibody isolated from a patient with
      Antiphospholipid Syndrome (APS). IS6 antibody was purified from hybridoma
      supernatant. Its pathogenic potentials were studied in an in vivo model of
      induced thrombosis. The expression of tissue factor (TF) and E-selectin on human
      umbilical vein endothelial cells (HUVEC) was determined by cyto-enzyme-linked
      immunosorbent assay. Transcription of TF mRNA was determined by quantitative real
      time-polymerase chain reaction (RT-PCR). In vivo, the thrombus size increased
      significantly when treated with IS6 compared with control-treated mice (5388 +/-
      1035 microm2 vs. 2845 +/- 1711 microm2). In vitro, IS6 induced significant
      expression of TF and E-selectin on HUVEC, when compared with control preparation
      (3.1- and 5.1-fold increase compared with the control-treated cells). RT-PCR
      analysis of TF mRNA transcription showed a 2.5-fold increase of IS6-treated cells
      over the value obtained with control-treated cells. Taken together, these data
      show that IS6 monoclonal anti-prothrombin antibody promotes thrombosis and this
      is associated with TF and E-selectin expression.

PMID- 16965391
TI  - Human homolog of Drosophila tumor suppressor Scribble negatively regulates cell
      cycle progression from G1 to S phase by localizing at the basolateral membrane in
      epithelial cells.
AB  - Drosophila tumor suppressor Scribble has been identified as an apical-basolateral
      polarity determinant in epithelia. A human homolog of Drosophila Scribble, human
      Scribble (hScrib), has been identified as a protein targeted by human
      papillomavirus E6 for the ubiquitin-mediated degradation dependent on E6AP, a
      cellular ubiquitin-protein ligase. Human Scribble is classified as a LAP protein,
      having leucine-rich repeats (LRRs) and PDZ domains. We investigated whether
      hScrib, which is thought to have a role in polarity determination based on the
      data of its Drosophila homolog, is involved in cell-cycle regulation and
      proliferation control of epithelia. Transfection of hScrib inhibits cell-cycle
      progression from G1 to S phase, and it up- and down-regulates expression of
      adenomatous polyposis coli and cyclins A and D1, respectively. Knockdown of
      hScrib expression by siRNA leads to cell-cycle progression from G1 to S phase. We
      explored functional domain mapping to reveal which domains of hScrib are critical
      for its cellular proliferation control and localization at the basolateral
      membrane. We found that LRRs and PDZ domain 1 are indispensable for hScrib to
      inhibit cell growth by blocking cell-cycle progression and to keep its proper
      localization. These data indicate that basolateral membrane localization of
      hScrib is closely related to its proliferation control. Our findings suggest the
      possibility that hScrib is involved in signal transduction to negatively regulate
      cell proliferation by localizing at the basolateral membrane of epithelial cells
      through LRRs and PDZ domains.

PMID- 16965392
TI  - Meat, milk, saturated fatty acids, the Pro12Ala and C161T polymorphisms of the
      PPARgamma gene and colorectal cancer risk in Japanese.
AB  - The peroxisome proliferator-activated receptor gamma (PPARgamma) gene plays
      important roles in energy homeostasis. To examine interactions between
      consumption of foods and fatty acids and the Pro12Ala and C161T (His447His)
      polymorphisms for colorectal cancer, we performed two case-control studies in
      Japanese. In study 1, there were 128 colorectal cancer cases and 238 non-cancer
      controls, and in study 2 there were 257 cases and 771 (age- and sex-matched) non
      cancer controls. Assessment of food and nutrients consumption in study 1 was via
      a nine-item questionnaire, while in study 2 assessment of consumption was
      according to a more detailed semiquantitative food frequency questionnaire.
      Consumption of foods and fatty acids was divided into low, moderate and high
      groups. The overall frequency of the Ala allele was <4%, and the frequencies of
      the Pro/Pro + C/C and Pro/Pro + (C/T + T/T) genotypes were 70-73% and 20-26%,
      respectively. Compared with subjects with low meat intake and the Pro/Pro + C/C
      genotype, those with high meat consumption and the same genotype had a stronger
      increased risk in study 1 [OR, 2.88; 95% CI, 1.14-7.30; P for trend = 0.02], but
      a positive association with processed meat consumption was greatest in those with
      the Pro/Pro + (C/T + T/T) genotype (P for trend = 0.05) in study 2. Likewise,
      high consumption of saturated fatty acids and milk appeared to confer marginal
      increased risk and stronger decreased risk, respectively, in those with the
      Pro/Pro and Pro/Pro + C/C genotypes (OR, 1.35 and 0.65; 95% CI, 0.93-1.96 and
      0.43-1.00; P for trend = 0.10 and 0.06). Further large-scale studies are needed
      to determine colorectal cancer risk according to relationships between the
      PPARgamma gene polymorphisms and dietary intakes of meat, processed meat, milk
      and saturated fatty acids in Japanese with very low frequency of the Ala allele.

PMID- 16965393
TI  - EphA4 receptor, overexpressed in pancreatic ductal adenocarcinoma, promotes
      cancer cell growth.
AB  - To isolate novel diagnostic markers and drug targets for pancreatic ductal
      adenocarcinoma (PDAC), we previously performed expression profile analysis of
      PDAC cells using a genome-wide cDNA microarray combined with laser
      microdissection. Among dozens of up-regulated genes identified in PDAC cells, we
      herein focused on one tyrosine kinase receptor, Eph receptor A4 (EphA4), as a
      molecular target for PDAC therapy. Immunohistochemical analysis validated EphA4
      overexpression in approximately half of the PDAC tissues. To investigate its
      biological function in PDAC cells, we knocked down EphA4 expression by siRNA,
      which drastically attenuated PDAC cell viability. In concordance with the siRNA
      experiment, PDAC-derivative cells that were designed to constitutively express
      exogenous EphA4 showed a more rapid growth rate than cells transfected with mock
      vector, suggesting a growth-promoting effect of EphA4 on PDAC cells. Furthermore,
      the expression analysis for ephrin ligand family members indicated the
      coexistence of ephrinA3 ligand in PDAC cells with EphA4 receptor, and knockdown
      of ephrinA3 by siRNA also attenuated PDAC cell viability. These results suggest
      that the EphA4-ephrinA3 pathway is likely to be a promising molecular target for
      pancreatic cancer therapy.

PMID- 16965394
TI  - Japan-US Cooperative Cancer Research Seminar on molecular epidemiological
      characteristics of lung and colon cancer development among atomic-bomb survivors,
      Bethesda, USA, February 23-24, 2006.

PMID- 16965395
TI  - Upregulation of fibroblast growth factor receptor 3 and epidermal growth factor
      receptors, in association with Raf-1, in urothelial dysplasia and carcinoma in
      situ after the Chernobyl accident.
AB  - The present study was carried out in order to examine the molecular status of
      selected growth factor receptors (GFR) in urinary bladder lesions, recently
      described by our group as representing 'Chernobyl cystitis'. Fibroblast growth
      factor receptor 3 (FGFR3), epidermal growth factor receptor 1 (EGFR1), EGFR2neu
      (a member of the same family), p53 and Raf-1 serine/threonine kinase expression
      were evaluated immunohistochemically in urinary bladder biopsies from 22 men with
      benign prostate hyperplasia (group 1). For comparison, 16 men with benign
      prostate hyperplasia and five women with chronic cystitis living in non-radio
      contaminated areas of the country were also investigated as controls (group 2).
      Additionally, 14 patients with dysplasia, carcinoma in situ (CIS) and primary
      urothelial carcinoma (UC) operated before the Chernobyl accident as well as 23
      patients with UC living in the radio-contaminated areas were included as pre- and
      post-Chernobyl UC groups 1 and 2, respectively. Chronic proliferative atypical
      cystitis ('Chernobyl cystitis') was observed in group 1 patients. Foci of
      dysplasia and CIS were found in 22 (100%) and 19 (86%) of the 22 cases,
      respectively; moreover, two small UC were also detected. Elevated levels of
      FGFR3, EGFR2/neu, p53 and to a lesser extent EGFR1 and Raf-1 expression in the
      urothelial dysplasia and CIS were evident for patients of group 1. Statistically
      significant differences in immunohistochemical scores for FGFR3, EGFR1, p53 and
      Raf-1 were observed between groups 1 and 2 and between group 1 and the post
      Chernobyl UC group 2, where a change in expression of EGFR2/neu was also noted. A
      significant decrease in FGFR3 expression in additional pre-Chernobyl UC group 1
      with dysplasia, CIS and UC compared with group 1 Chernobyl cystitis cases was
      detected. Our findings suggest that FGFR and EGFR signaling pathways, associated
      with p53 and Raf-1 activation, may contribute to multistage urothelial
      carcinogenesis caused by irradiation, through autocrine or paracrine growth
      stimulation.

PMID- 16965396
TI  - Diagnostic utility of aberrant methylation of tissue factor pathway inhibitor 2
      in pure pancreatic juice for pancreatic carcinoma.
AB  - The tissue factor pathway inhibitor 2 (TFPI-2) is a Kunitz-type serine proteinase
      inhibitor. Recently, the aberrant methylation of TFPI-2 was detected frequently
      in pancreatic carcinoma (PCa) tissues but not in normal pancreatic tissues. We
      analyzed the aberrant methylation of TFPI-2 in the pure pancreatic juice (PPJ)
      aspirated endoscopically from patients with various pancreatic diseases. Using
      the highly sensitive methylation-specific polymerase chain reaction (MSP) and
      quantitative MSP (Q-MSP) assay, we investigated the aberrant methylation of TFPI
      2 in nine human PCa cell lines and in the PPJ from patients with PCa, intraductal
      papillary mucinous neoplasms (IPMN) and chronic pancreatitis (CP). The incidence
      of aberrant TFPI-2 methylation was seven (77.8%) of nine PCa cell lines by Q-MSP.
      In cell lines, the expression of TFPI-2 mRNA by quantitative reverse
      transcription-polymerase chain reaction showed an inverse correlation to the
      aberrant methylation of TFPI-2. The incidence of aberrant TFPI-2 methylation in
      the PPJ was 21 (58.3%) of 36 PCa patients, three (17.6%) of 17 IPMN and one
      (4.8%) of 21 CP by MSP assay. Using a suitable cut-off value of 2.5 according to
      the receiver operating characteristic curve, the incidence of aberrant TFPI-2
      methylation in the PPJ by real-time MSP was 18 (62.1%) of 29 PCa patients, one
      (5.1%) of 17 IPMN and three (14.3%) of 21 CP, respectively. The incidence of
      quantitative TFPI-2 hypermethylation in the PPJ with PCa was significantly higher
      than that with IPMN (P < 0.001) or CP (P < 0.001). Moreover, the aberrant
      methylation rate of TFPI-2 in the PPJ was 100%, as observed (6/6) in the PCa
      patients with liver metastasis, and 86.7% (26/30) in stages IVa + IVb of PCa by Q
      MSP assay. These results suggest that promoter methylation of TFPI-2 in the PPJ
      may be a useful marker in the diagnosis and progression of PCa using an
      endoscopically feasible approach.

PMID- 16965397
TI  - Expression profile of LIT1/KCNQ1OT1 and epigenetic status at the KvDMR1 in
      colorectal cancers.
AB  - The human chromosome region 11p15.5 contains a number of maternally and
      paternally imprinted genes, and the LIT1/KCNQ1OT1 locus acts as an imprinting
      center in the proximal domain of 11p15.5. Loss of imprinting (LOI) of LIT1 and
      its correlation with methylation status at a differentially methylated region,
      the KvDMR1, were investigated in 69 colorectal cancer tissue specimens. LIT1
      expression profiles were also examined by RNA-fluorescence in situ hybridization
      in 13 colorectal cancer cell lines. In 69 colorectal cancer tissue specimens, LOI
      of LIT1 was observed in nine of the 17 (53%) informative cases. Moreover, LOI of
      LIT1 was only observed in tumor samples. In the cell lines, methylation status at
      the KvDMR1 correlated well with LIT1 expression profiles. Loss of expression of
      LIT1 also correlated with enrichment of H3 lysine 9 (H3-K9) dimethylation and
      reduction of H3 lysine 4 (H3-K4) dimethylation. Thus, LIT1 expression appears to
      be controlled by epigenetic modifications at the KvDMR1, although CDKN1C
      expression, which is considered to be controlled by LIT1, was not associated with
      epigenetic status at the KvDMR1 in some colorectal cancer cell lines. Therefore,
      these findings suggest that LOI of LIT1 via epigenetic disruption plays an
      important role in colorectal carcinogenesis, but it is not necessarily associated
      with CDKN1C expression.

PMID- 16965399
TI  - Emergence of Clostridium difficile-associated disease in North America and
      Europe.
AB  - The clinical spectrum of Clostridium difficile-associated disease (CDAD) ranges
      from diarrhoea to severe life-threatening pseudomembranous colitis. Although not
      always associated with previous antibiotic exposure, it is in the majority of
      cases. CDAD is recognised increasingly in a variety of animal species and in
      individuals previously not considered to be predisposed. C. difficile can be
      transmitted via personal contact or environmentally. The role of patients and
      healthcare workers who are symptom-free but colonised with C. difficile in the
      intestinal tract is unclear. C. difficile, with more than 150 PCR ribotypes and
      24 toxinotypes, has a pathogenicity locus (PaLoc) with genes encoding enterotoxin
      A (tcdA) and cytotoxin B (tcdB). Genes for the binary toxin are located outside
      the PaLoc, but the role of this toxin is unclear. The recently completed genome
      sequence of C. difficile 630 revealed a large proportion of 11% of mobile genetic
      elements, mainly in the form of conjugative transposons. Diagnostic assays
      include tests for the detection of C. difficile products or genes and culture
      methods for isolation of a toxin-producing bacterium. Enzyme immunoassays to
      detect toxin in faeces are widely available, with varying sensitivities and
      specificities. Despite practical drawbacks and sensitivity less than 100%, the
      cell cytototoxicity assay is still considered to be the standard. Rapid
      diagnostic assays are available on a limited scale and require much improvement.
      Molecular tests enable the detection of carriers of toxigenic and non-toxigenic
      strains, as does culture. It is highly recommended to culture C. difficile from
      toxin-positive faeces samples and to store isolates for future characterisation
      and typing. The financial impact of CDAD on the healthcare system is substantial
      (5-15,000 euro/case in England and $1.1 billion/year in the USA). Assuming a
      European Union population of 457 million, the potential cost of CDAD can be
      estimated to be 3000 million euro/year, and is expected to almost double over the
      next four decades. In North America, increasing rates of CDAD have been reported
      in Canada and the USA since March 2003, involving a more severe course, higher
      mortality, increased risk of relapse and more complications. This increased
      virulence is presumably associated with higher levels of toxin production by
      fluoroquinolone-resistant strains belonging to PCR ribotype 027, pulsed-field gel
      electrophoresis (PFGE) type NAP1, REA (restriction endonuclease analysis) type BI
      and toxinotype III. In Europe, outbreaks of CDAD due to the new, highly virulent
      strain of C. difficile PCR ribotype 027, toxinotype III have been recognised in
      75 hospitals in England, 16 hospitals in The Netherlands, 13 healthcare
      facilities in Belgium and nine healthcare facilities in France. These outbreaks
      are very difficult to control, and preliminary results from case-control studies
      indicate a correlation with fluoroquinolones and cephalosporins. Information
      concerning community-acquired cases of ribotype 027 is lacking, and data
      concerning its incidence in nursing homes are limited. European countries should
      first develop early-warning and response capabilities at a national level.
      Depending on the nature of the notifications received, countries should implement
      laboratory-based or patient-based surveillance systems in specific, targeted
      populations.

PMID- 16965400
TI  - Assessing genetic diversity between breeds for conservation.

PMID- 16965401
TI  - A comparison between multivariate Slash, Student's t and probit threshold models
      for analysis of clinical mastitis in first lactation cows.
AB  - Robust threshold models with multivariate Student's t or multivariate Slash link
      functions were employed to infer genetic parameters of clinical mastitis at
      different stages of lactation, with each cow defining a cluster of records. The
      robust fits were compared with that from a multivariate probit model via a pseudo
      Bayes factor and an analysis of residuals. Clinical mastitis records on 36 178
      first-lactation Norwegian Red cows from 5286 herds, daughters of 245 sires, were
      analysed. The opportunity for infection interval, going from 30 days pre-calving
      to 300 days postpartum, was divided into four periods: (i) -30 to 0 days pre
      calving; (ii) 1-30 days; (iii) 31-120 days; and (iv) 121-300 days of lactation.
      Within each period, absence or presence of clinical mastitis was scored as 0 or 1
      respectively. Markov chain Monte Carlo methods were used to draw samples from
      posterior distributions of interest. Pseudo-Bayes factors strongly favoured the
      multivariate Slash and Student's t models over the probit model. The posterior
      mean of the degrees of freedom parameter for the Slash model was 2.2, indicating
      heavy tails of the liability distribution. The posterior mean of the degrees of
      freedom for the Student's t model was 8.5, also pointing away from a normal
      liability for clinical mastitis. A residual was the observed phenotype (0 or 1)
      minus the posterior mean of the probability of mastitis. The Slash and Student's
      t models tended to have smaller residuals than the probit model in cows that
      contracted mastitis. Heritability of liability to clinical mastitis was 0.13-0.14
      before calving, and ranged from 0.05 to 0.08 after calving in the robust models.
      Genetic correlations were between 0.50 and 0.73, suggesting that clinical
      mastitis resistance is not the same trait across periods, corroborating earlier
      findings with probit models.

PMID- 16965402
TI  - Bayes factor for testing the genetic background of quantitative threshold traits.
AB  - The recent development of the Bayes factor methodology to test between nested
      competing models has allowed to evaluate the genetic component of continuous
      traits through a methodology based on the reparameterization of a variance
      component model in terms of intra-class correlation. In this study, we present a
      modification of that procedure to compare between threshold models that only
      differ in a bounded variable. An extra data-augmentation step is required to
      sample liability, an underlying continuous variable related with phenotypic
      records through an adequate number of thresholds. In this context, we describe a
      procedure to sample from a truncated multivariate normal distribution with non
      null covariances between records, taking as starting point the Cholesky
      factorization and the inclusion of linear restrictions. The method was tested by
      computer simulations with satisfactory results.

PMID- 16965403
TI  - Trait-associated expressed hepatic and intestine genes in cattle of different
      metabolic type--putative functional candidates for nutrient utilization.
AB  - The present study aimed at identifying bovine hepatic and intestinal DNA
      sequences expressed breed specifically as potential functional candidate genes
      for nutrient transformation. Transcript levels of 29 expressed sequence tags
      (ESTs) were analysed comparatively in the liver and intestine of growing
      Charolais and German Holstein bulls by real-time RT-PCR. In previous studies,
      these ESTs were characterized as differentially displayed in mRNA differential
      display of cows varying in metabolic type and harbouring single nucleotide
      polymorphisms. Breed-specific gene expression levels indicate significantly
      increased hepatic metabolic activity in Charolais and increased intestinal
      metabolic activity in German Holstein bulls. Transcript levels of six functional
      genes measured in liver (NDUFB8, NACA, UAP1, SAH) and intestine (FUS/TLS, APOC3),
      respectively, support this assumption. The observed coincidence of metabolic type
      specific expressed ESTs with variant ESTs showing breed-specific allele
      distribution points to functional genetic variants located in the vicinity of the
      analysed sequences. In addition, location of most of the breed specifically
      expressed ESTs within chromosome regions known to be affecting carcass and growth
      traits in cattle supports the putative candidate gene character of the ESTs
      identified.

PMID- 16965404
TI  - Analysis of genetic diversity and the determination of relationships among
      western Mediterranean horse breeds using microsatellite markers.
AB  - The distribution of genetic diversity and the genetic relationships among western
      Mediterranean horse breeds were investigated using microsatellite markers. The
      examined sample included seven Spanish and three Italian local horse breeds and
      populations, plus a Spanish Thoroughbred outgroup. The total number of animals
      examined was 682 (on average 62 animals per breed; range 20-122). The
      microsatellite marker set analysed provided 128 alleles (10.7 alleles per locus).
      Within-breed genetic diversity was always high (>0.70), with breeds contributing
      about 8% of the total genetic variability. The mean molecular coancestry of the
      entire population examined was 0.205, Losino being the breed that contributed
      most. In addition to Nei's standard and Reynolds' genetic distances, pair-wise
      kinship distance and molecular coancestry were estimated. Remarkably similar
      breed rankings were obtained with all methods. Clustering analysis provided an
      accurate representation of the current genetic relationships among the breeds.
      Determining coancestry is useful for analysing genetic diversity distribution
      between and within breeds and provides a good framework for jointly analysing
      molecular markers and pedigree information. An integrated analysis was undertaken
      to obtain information on the population dynamics in western Mediterranean native
      horse populations, and to better determine conservation priorities.

PMID- 16965405
TI  - High incidence of single nucleotide polymorphisms in the prion protein gene of
      native Brazilian Caracu cattle.
AB  - Different alleles of the human and ovine prion protein gene correlate with a
      varying susceptibility to transmissible spongiform encephalopathies. However, the
      pathogenic implications of specific polymorphisms in the bovine prion protein
      gene (PRNP) are only poorly understood. Previous studies on the bovine PRNP gene
      investigated common European and North American cattle breeds. As a consequence
      of decades of intensive breeding for specific traits, these modern breeds
      represent only a small fraction of the bovine gene pool. In this study, we
      analysed PRNP polymorphisms in the native Brazilian Caracu breed, which developed
      in geographical isolation since the 16th century. A total of 10 single nucleotide
      polymorphisms (SNPs) were discovered in the coding region of the Caracu PRNP
      gene. Eight of the SNPs occurred at high frequencies in Caracu cattle (variant
      allele frequencies = 0.10-0.76), but were absent or only rarely observed in
      European and North American breeds. One of the Caracu SNPs was associated with an
      amino acid exchange from serine to asparagine (f = 0.17). This SNP was not
      detected in Holstein-Friesian, Simmental and German Gelbvieh and was only rarely
      detected in beef cattle (f = 0.01). We found 17 haplotypes for PRNP in the Caracu
      breed.

PMID- 16965406
TI  - Genomic organization, localization and polymorphism of porcine PSMB10, a gene
      encoding the third beta-type proteasome subunit of 26S proteasome complex.
AB  - The proteasome subunit, beta type 10 (PSMB10) gene regulated by interferon-gamma
      is a core part of the 26S proteasome complex, which is an important protein
      degrading system. Isolation and characterization of swine PSMB10 revealed a
      conserved structure with other mammalian PSMB10 genes. An A/G nucleotide
      polymorphism in PSMB10 intron 2 and a C/T single nucleotide polymorphism in exon
      5 were detected by polymerase chain reaction restriction fragment length
      polymorphism. The allele frequencies were significantly different among
      Tongcheng, Landrace, Large White and Duroc. The porcine PSMB10 was mapped by
      somatic cell hybrid panel and radiation hybrid mapping on SSC6p14-p15, which is
      in good agreement with human-pig comparative maps.

PMID- 16965407
TI  - FISH mapping of 10 canine BAC clones harbouring genes and microsatellites in the
      arctic fox and the Chinese raccoon dog genomes.
AB  - Cytogenetic mapping of the arctic fox and the Chinese raccoon dog were performed
      using a set of canine probes derived from the Bacterial Artificial Chromosome
      (BAC) library. Altogether, 10 BAC clones containing sequences of selected genes
      (PAX3, HBB, ATP2A2, TECTA, PIT1, ABCA4, ESR2, TPH1, HTR2A, MAOA) and
      microsatellites were mapped by fluorescence in situ hybridization (FISH)
      experiments to chromosomes of the canids studied. At present, the cytogenetic map
      on the arctic fox and Chinese raccoon dog consists of 45 loci each. Chromosomal
      localization of the BAC clones was in agreement with data obtained by earlier
      independent comparative chromosome painting. However, two events of telomere-to
      centromere inversions were tentatively identified while compared with assignments
      in the dog karyotype.

PMID- 16965408
TI  - Detection of novel single-nucleotide polymorphisms (SNPs) in the CYP21 gene and
      association analysis of two SNPs for CYP21 and ESR2 with litter size in a
      commercial sow population.
AB  - Altogether 129 F1 sows from a commercial sow farm with at least four litters were
      genotyped for the oestrogen receptor 2 gene (ESR2) and cytochrome P450
      hydroxylase 21 gene (CYP21) and investigated for associations on the litter-size
      parameters: total number born and number born alive. Five novel polymorphisms
      were found in the 3'-untranslated region for the CYP21 gene. Genotype and allele
      frequencies for the CYP21 (position 3462G > A) single-nucleotide polymorphism
      (SNP) were 0.434 (GG), 0.504 (AG), 0.062 (AA) and 0.69 (G):0.31 (A),
      respectively. No association was found between this polymorphism and litter-size
      parameters. For the ESR2 gene, the SNP in exon 5 associated with an amino acid
      substitution MET (allele A) > VAL (allele G) was investigated. Only two genotypes
      were found leading to allele frequencies of 0.34 (A):0.66 (G). Only number born
      alive piglets were significantly increased for the AG genotype (p = 0.034) with
      11.64 piglets per sow and litter in comparison with the GG genotype, leading to
      only 10.96 piglets per sow and litter. From these data, it can be concluded that
      the investigated SNP of the ESR2 gene is associated with the number of liveborn
      piglets in the commercial population considered, and hence could be useful in
      selection for litter size. Therefore, this gene should be investigated in
      additional populations.

PMID- 16965409
TI  - Identification of single-nucleotide polymorphisms in 5' end and exons of the
      PRKAG3 gene in Hubbard White broiler, Leghorn layer, and three Chinese indigenous
      chicken breeds.
AB  - 5'-AMP-activated protein kinase plays an important role in regulating the level
      of ATP in the presence of metabolic stress. Previous studies revealed that
      polymorphisms in 5'-AMP-activated protein kinase gamma 3 subunit (PRKAG3) gene
      are associated with meat quality in pigs. In the present study, single-nucleotide
      polymorphisms (SNPs) in the 5'-end and exons of chicken PRKAG3 gene were
      identified with the method of single-strand conformation polymorphism in Hubbard
      ISA White broiler, Leghorn layer, and three Chinese indigenous chicken breeds,
      Tibet Chicken, Shouguang Chicken and Beijing Yellow Chicken. Two SNPs in the 5'
      end of the gene and 10 SNPs in exons 3, 4, 9 and 11, of which three caused amino
      acid substitutions, were identified in the PRKAG3 gene of the five chicken
      breeds. The results will facilitate further study on the association between the
      mutations of PRKAG3 and chicken meat quality.

PMID- 16965411
TI  - Imiquimod in the treatment of lentigo maligna.
AB  - BACKGROUND: Lentigo maligna (LM) is treated to prevent progression to lentigo
      maligna melanoma (LMM). Surgery remains the treatment of choice, although topical
      immunotherapy with imiquimod has recently become a popular alternative.
      OBJECTIVES: In this review, we have analysed the published literature relating to
      the use of imiquimod for LM, in order to understand better the utility of this
      treatment. METHODS: All English language studies relating to the use of imiquimod
      for LM were analysed up to January 2006. RESULTS: Eleven case reports and four
      open-label studies were identified, comprising a total of 67 patients who
      completed treatment with imiquimod for LM. There was significant variability in
      treatment schedules and regimens. Eight patients failed to respond, with LMM
      developing in two of these. In certain cases there were discrepancies between
      clinical and histological response with some patients clearing clinically but not
      histologically, and vice versa. Follow-up periods were short, exceeding 12 months
      in only five cases. CONCLUSIONS: Although imiquimod clearly has an effect on LM,
      this analysis of available studies has helped to identify concerns about its use.
      Without controlled evidence and prolonged follow up, the use of imiquimod for LM
      must still be considered experimental.

PMID- 16965412
TI  - Substance P receptor expression in human skin keratinocytes and fibroblasts.
AB  - BACKGROUND: There is increasing evidence that neuropeptides, especially substance
      P (SP), may be involved in the pathogenesis of cutaneous allergic inflammation
      (CAI). OBJECTIVES: To investigate expression of the SP receptor (neurokinin-1
      receptor, NK-1R) in human epidermal keratinocytes and dermal fibroblasts and its
      potential influence in CAI. METHODS: HaCaT cells (a human epidermal keratinocyte
      cell line) and dermal fibroblasts were cultured. The expression of NK-1R protein
      was examined by immunohistochemistry, and the mRNA level was detected by
      semiquantitative reverse transcriptase-polymerase chain reaction. The modulation
      of NK-1R expression in HaCaT cells and fibroblasts was detected by flow cytometry
      and Western blotting analysis. RESULTS: NK-1R expression was found in HaCaT cells
      and fibroblasts. The expression of NK-1R mRNA in fibroblasts was weaker than in
      HaCaT cells. SP and interferon (IFN)-gamma significantly upregulated the
      expression of NK-1R. [d-Arg(1), d-Trp(7,9) Leu(11)]-SP (Spantide I), a
      panspecific NK-1R antagonist, reduced the expression of NK-1R stimulated by SP.
      CONCLUSIONS: HaCaT cells and fibroblasts can express NK-1R at protein and
      transcription levels, and the expression was modulated by SP, IFN-gamma and
      Spantide I. This indicates that keratinocytes and fibroblasts are involved in the
      regulation of skin immunity and that NK-1R may play an important role in the
      pathogenesis of CAI.

PMID- 16965413
TI  - Psoriasis vulgaris in Chinese individuals is associated with PSORS1C3 and CDSN
      genes.
AB  - BACKGROUND: Besides the HLA-Cw*0602 allele, the psoriasis susceptibility 1
      candidate 3 (PSORS1C3) and corneodesmosin (CDSN) genes are two probable psoriasis
      susceptibility genes in the PSORS1 locus. The -79C, -26C and +246A alleles of the
      PSORS1C3 gene, the CDSN*971T allele, CDSN*TTC (619T-1236T-1243C) and CDSN*5 (619T
      1240G-1243C) are strongly associated with psoriasis in the caucasian population.
      Until now, no haplotype study of the PSORS1C3 and CDSN genes has been documented
      in Chinese patients with psoriasis vulgaris. OBJECTIVES: We aimed to determine
      whether genetic polymorphisms of the PSORS1C3 and CDSN genes were associated with
      an increased risk of psoriasis vulgaris in Chinese patients in Taiwan. METHODS:
      We investigated the PSORS1C3 and CDSN genes for disease association by direct
      sequencing in 178 patients with psoriasis vulgaris and 203 control subjects.
      Genotyping for HLA-Cw*0602, alpha-helix coiled-coil rod homologue (HCR) gene and
      single nucleotide polymorphism (SNP) n.9 was also carried out using a sequence
      based typing method. RESULTS: The PSORS1C3*582A allele, an SNP in the 3'
      untranslated region of the PSORS1C3 gene, was a major psoriasis vulgaris
      susceptibility allele in the Chinese population, and the association was much
      stronger in patients with early-onset psoriasis vulgaris (22.3% vs. 6.9%, odds
      ratio = 3.87, P(c) =0.0000072). The frequencies of CDSN*TTC and CDSN*971T were
      also significantly increased in patients with early-onset psoriasis vulgaris.
      Moreover, PSORS1C3*582A, SNP n.9*C, Cw*0602 and HCR*WWCC were in near complete
      linkage disequilibrium (LD) with each other; in contrast, the LD with the CDSN
      gene was not so strong. SNP n.9*C-Cw*0602-PSORS1C3*582A-HCR*WWCC was a major
      susceptibility haplotype in patients with early-onset psoriasis vulgaris (P < 10(
      7)) and this risk haplotype also carried CDSN*TTC and CDSN*971T. CONCLUSIONS: The
      PSORS1C3 and CDSN genes are important psoriasis susceptibility genes in Chinese
      patients with psoriasis vulgaris.

PMID- 16965414
TI  - Intercellular adhesion molecule-1: a consistent inflammatory marker of the
      cutaneous radiation reaction both in vitro and in vivo.
AB  - BACKGROUND: Radiation damage to skin is a key diagnostic and prognostic parameter
      for patients accidentally exposed to radiation. Moreover, skin is a target organ
      for crucial side-effects of routine radiotherapy. The pathophysiology of the
      cutaneous radiation reaction is in many respects still unknown. The acute
      inflammatory radiation reaction of skin has been shown to involve alterations in
      cell-cell and cell-matrix interactions, which are mediated by cellular adhesion
      molecules. OBJECTIVES: To evaluate the effect of ionizing radiation on
      intercellular adhesion molecule-1 (ICAM-1) expression in human skin cells.
      METHODS: Dermal monolayer cells, a three-dimensional skin model and skin biopsies
      were investigated for ICAM-1 expression after ionizing radiation using flow
      cytometry, quantitative reverse transcription-polymerase chain reaction and
      immunohistochemistry. ICAM-1 expression in monolayer cells pretreated with
      protein kinase inhibitors and dexamethasone prior to irradiation was analysed by
      flow cytometry. RESULTS: Using different sources of skin cells, we demonstrated a
      consistent upregulation of both ICAM-1 mRNA and protein expression by ionizing
      radiation. Blocking experiments revealed that tumour necrosis factor-alpha,
      another ICAM-1 inducer, does not account for the effect of radiation. Radiation
      induced upregulation of ICAM-1 expression was significantly attenuated by
      inhibitors to protein kinase C, mitogen-activated protein (MAP) ERK kinase, p38
      MAP kinase and phosphatidylinositol 3-kinase. The anti-inflammatory agent
      dexamethasone suppressed the effect of radiation on ICAM-1 expression, suggesting
      its usefulness to treat the cutaneous radiation reaction. CONCLUSIONS: Our data
      suggest that ICAM-1 is a consistent inflammatory parameter of the cutaneous
      radiation reaction both in vitro and in vivo that might provide new therapeutic
      options for diagnosis and treatment of effects of radiation.

PMID- 16965415
TI  - Skin colonization by Staphylococcus aureus in patients with eczema and atopic
      dermatitis and relevant combined topical therapy: a double-blind multicentre
      randomized controlled trial.
AB  - BACKGROUND: Staphylococcus aureus has a peculiar ability to colonize the skin of
      patients with eczema and atopic dermatitis (AD), and is consistently found in
      eczematous skin lesions in these patients. A correlation between the severity of
      the eczema and colonization with S. aureus has been demonstrated, and it has been
      determined that bacterial colonization is an important factor aggravating skin
      lesions. Patients colonized with S. aureus have been treated with antibiotics in
      several open and double-blind placebo-controlled studies, with conflicting
      results. OBJECTIVES: To investigate the colonizing features of S. aureus in the
      lesional and nonlesional skin of patients with eczema and AD in China and to
      compare the therapeutic effect of mupirocin plus hydrocortisone butyrate with
      vehicle ointment plus hydrocortisone butyrate. METHODS: A multicentre, double
      blind randomized trial was conducted. Eczema Area and Severity Index (EASI)
      scores were evaluated before the start of the trial and on the 7th, 14th and 28th
      day of treatment. Swabs for bacterial isolation were taken from lesional skin
      before the start of the trial and on the 7th, 14th and 28th day of treatment, and
      from nonlesional skin only before the start of the trial. A combination topical
      therapy with mupirocin plus hydrocortisone butyrate ointment was used in the
      experimental group, with vehicle ointment plus hydrocortisone butyrate ointment
      as a control. RESULTS: Of 327 patients enrolled in the study, 208 had eczema and
      119 had AD. Bacteria were isolated from 70.2% of lesional and 32.7% of
      nonlesional skin samples from patients with eczema, of which S. aureus accounted
      for 47.3% and 27.9%, respectively. Bacteria were isolated from 74.8% of lesional
      and 34.5% of nonlesional skin samples from patients with AD, of which S. aureus
      accounted for 79.8% and 80.5%, respectively. The colonization density of S.
      aureus was markedly higher in lesional than in nonlesional skin, both in patients
      with eczema and with AD (P < 0.01, P < 0.05), and was positively correlated with
      lesion severity. Considering the EASI scores before and after treatment and the
      final effective rate, good therapeutic effects were obtained in both the
      combination experimental groups and the control groups (P < 0.01), and there were
      no differences in the global therapeutic effect between the two groups in
      patients with eczema and with AD (P > 0.05). However, in patients with eczema
      with a clinical score of > 8 or in patients with AD with a clinical score of > 7,
      the therapeutic effect in the experimental groups was superior to that in the
      control groups (P < 0.05) on the 7th day of treatment. There were no differences
      between the two groups on the 14th and 28th days of treatment (P > 0.05).
      Following the improvement of symptoms and signs of eczema and AD, the positive
      rates of bacteria and S. aureus were reduced on the 7th day of treatment.
      CONCLUSIONS: This study confirmed that lesional skin of patients with eczema and
      AD was more frequently colonized with S. aureus than was nonlesional skin. The
      more severe the eczema, the higher the colonization rate of S. aureus, and S.
      aureus was also more often present in lesional and nonlesional skin in patients
      with AD than in those with eczema. Staphylococcus aureus infection is related to
      the pathogenesis of eczema and AD. An antibiotic-corticosteroid combination and
      corticosteroid alone both gave good therapeutic effect in eczema and in AD, and
      both reduced colonization by S. aureus. Early combined topical therapy is
      beneficial to patients with moderate to severe eczema and AD, and it is
      unnecessary to use antibiotics at later stages of disease or in mild eczema or
      AD.

PMID- 16965416
TI  - Assessment of epidermal subpopulations and proliferation in healthy skin,
      symptomless and lesional skin of spreading psoriasis.
AB  - BACKGROUND: The margin zone in spreading psoriatic lesions has frequently been
      used as a model to study the changes in epidermal proliferation, keratinization
      and inflammation during the transition from symptomless to lesional skin.
      However, the dynamics of the changes in the epidermal subpopulations-basal cells,
      transit amplifying cells and differentiated cells-have not been studied in the
      transition between symptomless and lesional skin. OBJECTIVES: To quantify in a
      dynamic model of the margin zone in psoriasis the characteristics of these
      subpopulations with respect to epidermal proliferation and differentiation.
      METHODS: From seven patients with active psoriasis, biopsies were taken from the
      distant uninvolved skin, outer margin, inner margin and centre of a spreading
      psoriatic plaque. Frozen sections were labelled immunofluorescently using direct
      immunofluorescence for Ki-67 and beta1 integrin and the Zenon labelling technique
      for keratin 6, 10 and 15. Digital photographs of the stained sections were
      quantitatively analysed. RESULTS: In the distant uninvolved skin the expression
      of beta1 integrin was decreased and keratin 15 expression was lost. In this area
      suprabasal cells expressed beta1 integrin and in the outer margin suprabasal
      cells expressed Ki-67. From the outer to the inner margin of the psoriasis
      plaque, which coincided with the appearance of the clinical lesion, there was a
      significant change in the various markers. The patchy expression of keratin 6 in
      the inner margin became homogeneous in the centre of the psoriasis plaque and
      here was also coexpression of keratin 6 and keratin 10 in a single cell.
      CONCLUSIONS: The present study provides additional evidence that the distant
      uninvolved skin has a prepsoriatic phenotype, which is the first step in a
      psoriatic cascade. The cascade between symptomless and lesional skin comprises
      first an abnormality in inflammation with involvement of beta1 integrin-dim cells
      (transit amplifying cells) subsequently eliciting an enlarged germinative
      compartment with increased recruitment of cycling epidermal cells and focal
      expression of proliferation-associated keratins, ultimately culminating in a more
      or-less homogeneous epidermis with massive recruitment of cycling epidermal cells
      and proliferation-associated keratinization.

PMID- 16965417
TI  - Dermoscopy in black people.
AB  - BACKGROUND: Little is known about the use of dermoscopy in nonwhite-skinned
      populations and whether it can influence diagnostic performance. OBJECTIVES: To
      evaluate for the first time the utility and efficacy of dermoscopy in a black
      population for the diagnosis of pigmented cutaneous lesions. METHODS: In total,
      100 consecutive clinically doubtful or equivocal pigmented skin lesions in black
      patients were submitted to dermoscopic examination. The lesions were observed
      using dermoscopy by two groups of dermatologists, one in Brazil (in vivo) and the
      other in Italy (on slide images). Besides diagnosis, each group recorded on the
      same type of form the dermoscopic features present. RESULTS: Of 100 clinically
      suspicious cases, 79 were Clark naevi, 15 seborrhoeic keratoses, four blue naevi,
      one dermatofibroma and one melanoma. The two groups of observers succeeded in
      identifying and classifying all the lesions to such a margin of diagnostic
      accuracy that only a few cases (three Clark naevi) were subjected to surgical
      excision to confirm diagnosis. CONCLUSIONS: Darker pigmentation of the skin does
      not impede the identification of single dermoscopic features. As in lighter
      skinned populations, dermoscopy in black people can also lead to early and
      accurate diagnosis of melanoma, thereby significantly reducing the number of
      unnecessary excisions.

PMID- 16965418
TI  - Evaluation of the atrophogenic potential of different glucocorticoids using
      optical coherence tomography, 20-MHz ultrasound and profilometry; a double-blind,
      placebo-controlled trial.
AB  - BACKGROUND: Skin atrophy is one of the main side-effects of topical
      corticosteroid therapy. Although the use of high-frequency ultrasound is an
      established method that has been studied previously, it allows measurements of
      the slow-reacting dermal thickness only. OBJECTIVES: To investigate the
      decreasing epidermal thickness, which occurs earlier, we used optical coherence
      tomography (OCT), a high-resolution noninvasive imaging technique, and compared
      it with 20-MHz ultrasound and profilometry. PATIENTS/METHODS: In this double
      blind placebo-controlled trial 20 healthy volunteers applied four different
      corticosteroids and the cream base formulation as placebo to the volar part of
      both arms once a day over a 4-week period. The epidermal thickness, the dermal
      thickness and the skin surface roughness were assessed using OCT, high-frequency
      ultrasound and profilometry. RESULTS: Each of the three methods allowed the
      detection and monitoring of significant corticosteroid-induced skin atrophy and
      its reversibility. The changes correlated with the potency of the steroids. The
      epidermal thickness decreased significantly in all test areas, even in the
      placebo and the untreated fields. As expected, the reduction in epidermal
      thickness was more pronounced and could be detected earlier by OCT than the
      reduction of dermal thickness using ultrasound. The epidermal surface roughness
      investigated using profilometry showed a slight smoothing. CONCLUSIONS: OCT
      allows a simple, fast and noninvasive in vivo measurement of the epidermal
      thickness. To evaluate the atrophogenic potential of corticosteroids it is more
      suitable than high-frequency ultrasound as epidermal thickness decreases earlier.
      In addition, epidermal thickness is a more sensitive indicator of steroid atrophy
      as the degree of thinning is much higher compared with the dermal atrophy.
      Profilometry might give further information; however, it would not be suitable
      for clinical use as the results were generally less pronounced. In the future,
      OCT might be useful to detect corticosteroid-induced side-effects at the
      beginning for monitoring the therapy.

PMID- 16965419
TI  - A study examining inter- and intrarater reliability of three scales for measuring
      severity of psoriasis: Psoriasis Area and Severity Index, Physician's Global
      Assessment and Lattice System Physician's Global Assessment.
AB  - BACKGROUND: There is a lack of consensus as to the best way of monitoring
      psoriasis severity in clinical trials. The Psoriasis Area and Severity Index
      (PASI) is the most frequently used system and the Physician's Global Assessment
      (PGA) is also often used. However, both instruments have some drawbacks and
      neither has been fully evaluated in terms of 'validity' and 'reliability' as a
      psoriasis rating scale. The Lattice System Physician's Global Assessment (LS-PGA)
      scale has recently been developed to address some disadvantages of the PASI and
      PGA. OBJECTIVES: To evaluate the inter-rater and intrarater reliability of the
      PASI, PGA and LS-PGA. METHODS: On the day before the study, 14 dermatologists
      (raters), with varied experience of assessing psoriasis, received detailed
      training (2.5 h) on use of the scales. On the study day, each rater evaluated 16
      adults with chronic plaque psoriasis in the morning and again in the afternoon.
      Raters were randomly assigned to assess subjects using the scales in a specific
      sequence, either PGA, LS-PGA, PASI or PGA, PASI, LS-PGA. Each rater used one
      sequence in the morning and the other in the afternoon. The primary endpoint was
      the inter-rater and intrarater reliability as determined by intraclass
      correlation coefficients (ICCs). RESULTS: All three scales demonstrated
      'substantial' (a priori defined as ICC > 80%) intrarater reliability. The inter
      rater reliability for each of the PASI and LS-PGA was also 'substantial' and for
      the PGA was 'moderate' (ICC 75%). CONCLUSIONS: Each one of the three scales
      provided reproducible psoriasis severity assessments. In terms of both intrarater
      and inter-rater reliability values, the three scales can be ranked from highest
      to lowest as follows: PASI, LS-PGA and PGA.

PMID- 16965420
TI  - Intravenous immunoglobulin-associated arterial and venous thrombosis; report of a
      series and review of the literature.
AB  - BACKGROUND: To date, the prevalence of intravenous immunoglobulin (IvIg)-related
      thrombotic complications has not been evaluated in patients with autoimmune
      disorders followed up in Departments of Internal Medicine. OBJECTIVES: To assess
      prevalence and characteristics of IvIg-related thrombotic complications in
      patients with autoimmune disorders receiving IvIg therapy; to evaluate the
      predictive factors for onset of IvIg-related thrombotic manifestation in
      patients, and to detect patients at risk for these types of complications.
      PATIENTS AND METHODS: The medical records of 46 patients with autoimmune
      disorders who were given IvIg therapy at our Department of Internal Medicine
      between January 2002 and December 2004 were reviewed. RESULTS: Among the 46
      patients, nine exhibited IvIg-associated severe complications (19.6%). Six
      patients (13%) developed IvIg-related thrombotic complications. Thrombotic
      complications frequently occurred during IvIg infusion (50%), although they were
      also observed within 1-8 days following IvIg infusion in other patients. IvIg
      related thrombotic complications consisted of: deep venous thrombosis or
      pulmonary embolism (n = 3), myocardial infarction (n = 2) and stroke (n = 1). The
      outcome of thrombotic complications was favourable in all patients, after
      appropriate therapy institution. Older age, history of associated arterial
      hypertension and hypercholesterolaemia were more common in the group of patients
      with IvIg-related thrombotic complications. CONCLUSIONS: Our study demonstrates
      that IvIg-related thrombotic arterial/venous complications are not uncommon in
      patients with autoimmune disorders (13% of patients). Nevertheless, patients, who
      are followed up in Departments of Internal Medicine often have concomitant
      disorders placing them at increased risk to develop IvIg-related thrombotic
      complications; the latter may also explain the high rate of IvIg-related
      thrombosis in our cohort. Our series further indicates that patients should be
      monitored closely for these types of adverse events during the whole period of
      IvIg therapy, as thrombotic manifestations occurred in patients who had received
      multiple IvIg infusions without exhibiting complications. In addition, our
      results suggest that it is questionable to initiate IvIg therapy in patients
      presenting with predictive factors of thrombotic complications; in this subgroup
      of patients, IvIg should be prescribed cautiously, after re-weighing risk-benefit
      considerations.

PMID- 16965421
TI  - Expression of cytokines and chemokine receptors in the cutaneous lesions of
      erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis.
AB  - BACKGROUND: Erythema multiforme (EM) and Stevens-Johnson syndrome/toxic epidermal
      necrolysis (SJS/TEN) are caused by a dysregulation of cellular immunity.
      OBJECTIVES: To evaluate further the potential role of certain cytokines and
      chemokine receptors in cutaneous lesions of patients affected by EM and SJS/TEN
      and to establish whether such diseases are polarized preferentially towards a T
      helper (Th) 1 or Th2 pattern. METHODS: Biopsy specimens from eight patients with
      EM, six with SJS/TEN and three healthy controls were stained for
      immunohistochemical examination using the alkaline phosphatase-antialkaline
      phosphatase method. The monoclonal antibodies used included those to tumour
      necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-2, IL-5, IL
      13, receptor 3 for C-C chemokines (CCR3), receptor 3 for C-x-C chemokines (CXCR3)
      and CXCR4. RESULTS: The SJS/TEN specimens showed significantly higher expression
      of all the cytokines and chemokine receptors (except CXCR3) tested than the EM
      specimens. Both lesional series showed significantly higher expression of all the
      receptors tested than the healthy control specimens, with the sole exception of a
      lower expression of CCR3 in EM specimens. Comparison between molecules associated
      with a Th1 or Th2 response revealed a predominance of Th1 response in EM and no
      significant imbalance between Th1 and Th2 in SJS/TEN. CONCLUSIONS: We have
      provided further evidence that TNF-alpha is strongly expressed in SJS/TEN lesions
      and therefore it may be involved in the epidermal necrosis featured in such
      diseases. IFN-gamma may play an important role both in EM and SJS/TEN. IL-2, IL-5
      and IL-13 may contribute to the cutaneous immunoinflammation in these diseases.
      Chemokine receptors may be involved strongly in the recruitment of inflammatory
      cells in lesional skin. In our cases we found a sharp polarization towards a Th1
      pattern in EM, while the SJS/TEN lesions showed a mixed Th1/Th2 pattern.

PMID- 16965422
TI  - European patient perspectives on the impact of psoriasis: the EUROPSO patient
      membership survey.
AB  - BACKGROUND: EUROPSO (European Federation of Psoriasis Patient Associations)
      undertook a Europe-wide survey examining quality of life and patients'
      perspectives on treatment and their disease. OBJECTIVES: To explore patients'
      perspectives of psoriasis on their lifestyle and well-being and to gain insight
      into the effectiveness of and satisfaction with currently available therapies for
      psoriasis. METHODS: Self-administered questionnaires (n = 50,500) were mailed to
      members of psoriasis patient associations in Belgium, the Czech Republic,
      Finland, France, Germany, Italy and the Netherlands. RESULTS: Responses were
      received from 18,386 patients (36%), of whom 17,990 had psoriasis. Mean age at
      onset of psoriasis was 30.5 years, 59% of respondents had self-reported moderate
      to severe psoriasis (3% or greater body surface area involvement) and 30% had
      been diagnosed with psoriatic arthritis. The mean Psoriasis Disability Index
      score was 12.2 (25% of the maximum score), increasing to 21 (44%) in patients
      with more than 10% body surface area involvement. The greatest impact was on
      activities of daily living, especially affecting clothing choice, bathing routine
      and sporting activities. Overall, 77% replied that psoriasis was a problem or a
      significant problem. While patients were satisfied with the information and care
      from their dermatologist (40% highly satisfied), available treatment options were
      less satisfactory, with over 70% reporting only low to moderate satisfaction.
      CONCLUSIONS: This is the largest survey of people with psoriasis in Europe and
      shows that psoriasis has a profound impact on quality of life.

PMID- 16965423
TI  - Photopatch testing of 1155 patients: results of the U.K. multicentre photopatch
      study group.
AB  - BACKGROUND: Photoallergic contact dermatitis can be difficult to diagnose if not
      appropriately investigated. Currently, the most common U.K. photoallergens appear
      to be sunscreen chemicals. The investigation of choice is photopatch testing
      (PPT), which is probably underused. In part, this is due to differences in
      methodology and results interpretation. OBJECTIVES: To conduct PPT using a group
      of sunscreen chemicals, defined indications and a standardized methodology
      including interpretation and relevance of reactions in patients attending for
      investigation at 17 centres across the U.K., Ireland and the Netherlands.
      METHODS: Patients (n = 1155) who fulfilled the inclusion criteria were
      investigated with PPT using sunscreen chemicals in addition to suspected topical
      products. Readings were taken at 24, 48 and 72 h following standardized
      ultraviolet A irradiation (5 J cm(-2)). The clinical relevance of any reaction
      was recorded. RESULTS: Of the 1155, 130 had allergic reactions (11.3%). Of these,
      51 had photoallergy (PA) (4.4%), 64 had contact allergy (CA) (5.5%), and 15
      patients had combined PA and CA (1.3%). Multiple PA was seen in some. The most
      common photoallergen was benzophenone-3 (27 reactions; 21%). Most reactions (60%)
      were clinically relevant. The most common indication for testing in patients
      found to have PA was a history of reacting to a sunscreen (41%). The other 59%
      had an exposed-site dermatitis/skin problem or a photodermatosis. Some centres (n
      = 8) performed readings after the standard 48-h reading, and an extra 32 PA and
      22 CA reactions were detected, which were not evident at 48 h. A new
      photoallergen (octyl triazone) was detected in two patients. CONCLUSIONS:
      Sunscreen PA and CA are probably equally uncommon. Most reactions, of both
      reaction types, were relevant clinically. A large proportion of patients (59%)
      found to have PA was unaware of reacting to a sunscreen chemical, suggesting that
      PA should be considered as an explanation in any exposed-site dermatitis.
      Although this study focused on reactions at 48 h postirradiation, readings
      performed up to 96 h, while inconvenient, add value by detecting additional
      relevant responses. A previously unknown photoallergen was found, highlighting
      the need for awareness of novel photoallergens in the marketplace. A standardized
      PPT method not only encourages more use of this investigation, but also
      facilitates comparison of results between centres and so will improve our
      understanding of PA.

PMID- 16965424
TI  - Investigation of the mechanism of action of nonablative pulsed-dye laser therapy
      in photorejuvenation and inflammatory acne vulgaris.
AB  - BACKGROUND: Nonablative lasers are widely used for treatment of wrinkles,
      atrophic scars and acne. These lasers stimulate dermal remodelling and collagen
      production, but the early molecular stimulus for this is unknown. The mechanism
      of nonablative lasers in inflammatory acne is variously suggested to be damage
      either to sebaceous glands or to Propionibacterium acnes. Their effects on
      cytokine production are unknown. OBJECTIVES: To assess the in vivo effects of a
      short pulse duration nonablative pulsed-dye laser (NA-PDL) previously used for
      photorejuvenation and treatment of acne, on cytokine production, P. acnes
      colonization density and sebum excretion rate (SER). METHODS: We examined the
      effect of NA-PDL (NliteV; Chromogenex Light Technologies, Llanelli, U.K.) on P.
      acnes colonization before and after laser therapy using a scrub-wash technique
      and culture at 0 and 24 h (n = 15), on SER using absorptive tape at 0, 2, 4, 8
      and 12 weeks (n = 19) and on cytokine mRNA using reverse transcription-polymerase
      chain reaction from skin biopsies at 0, 3 and 24 h (n = 8). Results NA-PDL had no
      effect on P. acnes or SER. Transforming growth factor (TGF)-beta1 mRNA increased
      fivefold after 24 h and 15-fold in two subjects (P = 0.012). CONCLUSIONS: TGF
      beta is known to be a potent stimulus for neocollagenesis and a pivotal
      immunosuppressive cytokine which promotes inflammation resolution. Its
      upregulation by NA-PDL provides a possible unifying molecular mechanism linking
      stimulation of dermal remodelling in photorejuvenation with inhibition of
      inflammation in acne. Damage to P. acnes or sebaceous glands cannot explain the
      effect of this device in acne.

PMID- 16965425
TI  - Molecular staging of lymph nodes from 60 patients with mycosis fungoides and
      Sezary syndrome: correlation with histopathology and outcome suggests prognostic
      relevance in mycosis fungoides.
AB  - BACKGROUND: Histological evidence of lymph node involvement is associated with a
      poor prognosis in patients with cutaneous T-cell lymphoma (CTCL). OBJECTIVES: To
      determine whether T-cell receptor (TCR) gene analysis is of prognostic relevance
      in CTCL. METHODS: TCR gene analysis was performed on lymph node specimens from 60
      patients with mycosis fungoides (MF) and Sezary syndrome (SS) using a highly
      sensitive polymerase chain reaction (PCR)/single-strand conformational
      polymorphism analysis and results were correlated with skin, overall clinical and
      histological lymph node stages. RESULTS: The frequency with which a T-cell clone
      was detected in lymph node samples from patients with MF increased with skin
      stage, overall clinical stage and with the degree of histological involvement:
      six of 19 patients with uninvolved lymph nodes or limited histological
      involvement (LN0-2) and 13 of 14 patients with advanced histological involvement
      (LN3-4) had a detectable T-cell clone. In SS, 22 of 27 patients had a detectable
      lymph node T-cell clone. The clonal patients had a poorer prognosis than
      nonclonal patients (median survival from biopsy of > 72 months vs. 16 months for
      MF and 41.5 vs. 16.5 months for SS). Regression analysis confirmed that TCR gene
      analysis identifies a group of MF patients with a worse prognosis (P = 0.013).
      However, the molecular lymph node stage did not provide independent prognostic
      information in this cohort of patients in multivariate analysis. CONCLUSIONS:
      Molecular staging in MF and SS using a PCR-based method for TCR gene analysis
      provides additional information to histological examination. Specifically, this
      study identified a group of MF patients with early lymph node involvement with a
      poorer prognosis. However, a larger prospective study of patients with MF and
      early histological lymph node involvement is required to confirm whether
      molecular staging of lymph nodes provides independent prognostic information in a
      multivariate model.

PMID- 16965426
TI  - Tenascin-C patterns and splice variants in actinic keratosis and cutaneous
      squamous cell carcinoma.
AB  - BACKGROUND: Tenascin-C (Tn-C) is an extracellular matrix protein with multiple
      functions that is present at low levels in normal tissues, but which is highly
      present in various tumours. The mRNA expression and protein level of Tn-C
      including its various isoforms have not been investigated comprehensively so far
      in cutaneous squamous cell carcinoma (SCC) and the precursor lesion actinic
      keratosis (AK). OBJECTIVES: To assess the dysregulated expression and splice
      variants of Tn-C in cutaneous squamous cell dysplasia and carcinoma. METHODS:
      Biopsies from 66 patients (or representative subsets) that comprised 25 specimens
      from normal skin, 19 AK and 22 cutaneous SCC were analysed for Tn-C splice
      variants using splice-specific primers. The amount of Tn-C mRNA was investigated
      by quantitative real-time reverse transcription-polymerase chain reaction. In
      addition, the presence of Tn-C protein was analysed in sections of paraffin
      embedded tissues using immunohistochemistry. RESULTS: The large Tn-C splice
      variant was present in only 5% of normal skin samples, in comparison with 63% of
      AK (P < 0.001) and 88% of SCC (P < 0.001). Tn-C mRNA expression was significantly
      increased in AK and SCC compared with normal skin (P < 0.001). The corresponding
      proteins were rarely detected in cells of the vascular epithelial layers and
      perifollicular layers of some normal skin specimens, and their spatial
      localization expanded into the papillary dermis of AK. The largest amount and the
      widest distribution were found in samples of SCC, in which Tn-C was located in
      the basal cells at the tumour invasion front and additionally in the papillary
      dermis and reticular dermis. CONCLUSIONS: Tn-C is present in the dermis, its
      expression is increased during skin cancer development, and the large splice
      variant is characteristic for AK and SCC, which may prove useful for diagnostic
      approaches in cutaneous SCC.

PMID- 16965427
TI  - Is head and neck melanoma a distinct entity? A clinical registry-based
      comparative study in 5702 patients with melanoma.
AB  - BACKGROUND: The head and neck region is more heavily exposed to ultraviolet (UV)
      radiation than any other body site. Therefore, cutaneous malignant melanoma (CMM)
      of the head and neck area is proposed to have notable differences from melanoma
      at other body sites regarding clinicopathological features and survival of
      patients. OBJECTIVES: The present retrospective study based on clinical registry
      data aims to compare clinical features and prognostic factors of head and neck
      melanoma (HNM) vs. melanoma at other anatomical regions (MOR) in order to detect
      differences which may be associated to the mode of sun exposure. METHODS: The
      clinical records and histopathological findings of 844 patients with clinical
      stage I and II invasive HNM were compared with the data of 4858 patients with
      MOR. Survival analysis was performed using the Kaplan-Meier estimate, and the
      multivariate Cox proportional hazard model was used to evaluate independent
      prognostic factors. RESULTS: Melanoma density was clearly higher for HNM than for
      MOR: this was particularly true for the face, where it was elevated by a factor
      of 2.6. There was a higher male/female ratio in patients with HNM and they were
      significantly older than patients with MOR (P < 0.0001). Breslow tumour thickness
      did not differ between HNM and MOR. However, CMMs at the scalp were significantly
      thicker and to a higher degree ulcerated. Concerning clinicopathological CMM
      subtypes, there was an increased proportion of lentigo maligna melanoma among HNM
      and of nodular melanoma in the scalp and neck regions. Excision margins were
      narrower and the rate of complete primary excision was lower in HNM than in MOR.
      Overall, there was no significant statistical difference in cumulative 10-year
      survival rates according to Kaplan-Meier estimates among patients with HNM
      (84.6%) and MOR (87.8%). Tumour thickness turned out to be the variable with the
      highest prognostic impact followed by ulceration in both HNM and MOR.
      CONCLUSIONS: In relation to the skin surface significantly more CMMs were found
      in the head and neck area than in other anatomical regions. This might indicate,
      but does not prove, that UV exposure promotes the development of CMM. Although
      HNM showed specific clinicopathological features, prognosis remained unaffected.
      Thus HNM seems not to be a distinct subtype of CMM.

PMID- 16965428
TI  - Characteristics of extrinsic vs. intrinsic atopic dermatitis in infancy:
      correlations with laboratory variables.
AB  - BACKGROUND: Atopic dermatitis (AD) has been divided into the extrinsic type (ADe)
      and the intrinsic type (ADi) according to the serum IgE levels and the presence
      or absence of allergen-specific IgE. Although previous studies have demonstrated
      differences in the various immunological parameters, the characteristics of AD in
      infancy have rarely been reported. OBJECTIVES: Our study was performed to analyse
      the correlations between the laboratory parameters of infantile ADe and ADi.
      METHODS: We recruited 237 infants with AD and checked the SCORAD index, the
      number of peripheral blood eosinophils, the serum eosinophil cationic protein
      (ECP) levels, the total serum IgE levels and the specific serum IgE levels in all
      the patients. We also checked the serum interleukin (IL)-4 and IL-5 levels in 20
      patients with ADe and in 20 with ADi. RESULTS: This study showed many peculiar
      characteristics of infantile AD. In infancy, ADi was more prevalent than ADe. The
      eosinophil count, the ECP level and the SCORAD in ADi were lower than in ADe.
      Furthermore, a group of patients without characteristics of ADi or ADe could be
      identified. We tentatively classify this group as indeterminate type (ADind) and
      propose it as a separate entity. The clinical severity was well correlated with
      the eosinophil count and the serum ECP levels in ADe and ADi. Therefore these two
      parameters could be used as clinical severity markers in infancy. Infants are
      more allergic to food, and the variety of specific allergenic responses was
      connected with clinical severity. A higher eosinophil count, a higher ECP level
      and a higher detection rate of IL-5 in the peripheral blood of infants with ADe
      means that eosinophils have a more prominent role in ADe than in ADi.
      CONCLUSIONS: Infantile AD has many distinctive features in its laboratory
      variables as compared with AD in other age groups. Clinicians should recognize
      these facts when they deal with infants with AD, and further studies are
      warranted on the natural course of infantile AD.

PMID- 16965429
TI  - Economic evaluation of methyl aminolaevulinate-based photodynamic therapy in the
      management of actinic keratosis and basal cell carcinoma.
AB  - BACKGROUND: Various effective therapeutic options are currently available for the
      treatment of actinic keratosis (AK) and basal cell carcinoma (BCC), but none is
      perfect. Poor cosmesis resulting from surgical procedures and skin irritation
      induced by topical agents remain significant problems. OBJECTIVES: To evaluate
      the cost-effectiveness of a recent approach, methyl aminolaevulinate-based
      photodynamic therapy (MAL-PDT; Metvix; Galderma, Lausanne, Switzerland) in AK and
      BCC. METHODS: A medical decision tree was developed for simulation of all
      possible outcomes associated with the medical decision to apply MAL-PDT or a
      comparator. The time horizon was 1 year for AK and 5 years for BCC. The
      comparators were cryotherapy in AK and excision surgery in BCC. Clinical data for
      the model were obtained from the literature. Data on medical management resulted
      from a Delphi panel performed among 12 Belgian dermatologists. Based on the
      model, the cost per full responder was calculated, whereby a responder was
      defined as a patient with all lesions clinically responding and showing an
      excellent cosmetic result. RESULTS: MAL-PDT is a more expensive treatment
      compared with cryotherapy for AK. However, the cost per full responder is
      comparable with cryotherapy (euro363 and euro379, respectively). Incremental cost
      per extra full responder is euro401. Incremental cost per full responder is
      euro469 for nodular BCC and euro251 for superficial BCC, both compared with
      excision surgery. CONCLUSIONS: The results suggest that MAL-PDT is a cost
      effective intervention in AK taking a 1-year time horizon, if society is willing
      to pay euro1.50 per day of response, and that MAL-PDT is better value for money
      than excision in BCC, taking a 5-year time horizon.

PMID- 16965430
TI  - Topical application of 5-aminolaevulinic acid, methyl 5-aminolaevulinate and
      hexyl 5-aminolaevulinate on normal human skin.
AB  - BACKGROUND: 5-Aminolaevulinic acid (ALA) and its ester derivatives are used in
      photodynamic therapy. Despite extensive investigations, the differences in
      biodistribution and pharmacokinetics of protoporphyrin IX (PpIX) induced by ALA
      and its derivatives are still not well understood, notably for humans.
      OBJECTIVES: To study porphyrin accumulation after topical application of ALA and
      two of its ester derivatives in normal human skin. METHODS: Creams containing
      0.2%, 2% and 20% (w/w) of ALA, methyl 5-aminolaevulinate (MAL) and hexyl 5
      aminolaevulinate (HAL) were applied on normal human skin of six volunteers. The
      amount and distribution of porphyrins formed in the skin was investigated
      noninvasively by means of fluorescence spectroscopy. RESULTS: Fluorescence
      emission and excitation spectra exhibited similar spectral shapes for the all
      drugs, indicating that mainly PpIX was formed. Low concentrations (0.2% and 2%)
      of MAL induced considerably less PpIX in normal human skin than similar
      concentrations of ALA and HAL. A high concentration (20%) of ALA gave higher PpIX
      fluorescence in normal human skin than was found for MAL and HAL. CONCLUSIONS:
      The concentrations inducing half of the maximal PpIX fluorescence are around 2%
      for ALA, 8% for MAL and 1% for HAL.

PMID- 16965431
TI  - A comparison of twice-daily calcipotriol ointment with once-daily short-contact
      dithranol cream therapy: a randomized controlled trial of supervised treatment of
      psoriasis vulgaris in a day-care setting.
AB  - BACKGROUND: Calcipotriol has become a first-line treatment for psoriasis. Its
      efficacy and safety have been shown in many comparative clinical trials carried
      out in outpatients. In a comparative study in patients visiting the outpatient
      department once every 14 days, it was shown that calcipotriol was more effective
      and better tolerated compared with dithranol. OBJECTIVES: To compare the clinical
      efficacy of calcipotriol ointment with that of dithranol cream in a supervised
      treatment regimen. METHODS: In a multicentre randomized controlled trial in six
      centres in the Netherlands, 106 patients with chronic plaque psoriasis were
      included, 54 receiving calcipotriol ointment twice daily and 52 dithranol cream
      once daily. Patients were treated at the day-care centre, using the care
      instruction principle of daily visits during the first week and twice-weekly
      visits subsequently for up to 12 weeks. RESULTS: This study failed to prove that
      calcipotriol is as efficacious as dithranol when used in a day-care setting
      (noninferiority test). The mean percentage reduction in Psoriasis Area and
      Severity Index from baseline to end of treatment was 57.0% in the calcipotriol
      group vs. 63.6% in the dithranol group. However, the two-sided test for
      superiority indicated no statistically significant difference between the
      treatment groups (P = 0.39). At the end of treatment, 15% of the patients treated
      with calcipotriol ointment and 25% of those treated with dithranol cream did not
      require any further treatment. Although calcipotriol ointment appeared to be more
      effective during the first 8 weeks, a difference was no longer apparent at 12
      weeks. In comparison with the high number of drop-outs due to cutaneous side
      effects in the calcipotriol group, the frequency of a tolerable degree of
      irritation appeared to be higher in patients treated with dithranol. However,
      concomitant corticosteroid treatment of dithranol irritation in seven patients
      may have contributed to this difference between both treatments. Moreover,
      patients receiving therapy with calcipotriol ointment experienced fewer
      application-related skin and subcutaneous tissue disorders than patients treated
      with dithranol cream: 21 of 53 (40%) and 37 of 52 (71%), respectively. This
      difference is statistically significant (P = 0.001). CONCLUSIONS: The hypothesis
      that calcipotriol ointment might be at least as effective as dithranol cream in
      the day-care setting could not be proven in the present study. Whereas
      calcipotriol has become a mainstay in the routine outpatient treatment of
      psoriasis not requiring a day-care setting, dithranol treatment, being difficult
      as a routine outpatient therapy, has increased efficacy and improved tolerability
      if the treatment is carried out in a day-care setting.

PMID- 16965432
TI  - Initial experience with routine administration of etanercept in psoriasis.
AB  - BACKGROUND: Etanercept and efalizumab recently became available and reimbursed
      for routine use in severe psoriasis in the Netherlands. The criteria for
      reimbursement are Psoriasis Area and Severity Index (PASI) > or = 10 (or Skindex
      29 > or = 35 if PASI > or = 8 and < 10) and ineffectiveness of ultraviolet (UV)
      B/psoralen plus UVA, methotrexate and ciclosporin, or a contraindication to or
      serious side-effect(s) during these treatments. OBJECTIVES: We hypothesized: (i)
      that efficacy would be lower than that obtained in published phase II and III
      studies because (a) resistance to all conventional therapies as a reimbursement
      condition would select for more resistant cases and (b) inclusion would be more
      restricted to severe cases (higher PASI), and (ii) that efficacy would be lower
      in obese patients due to the possible role of adipose tissue in tumour necrosis
      factor (TNF)-alpha homeostasis. METHODS: We treated 50 patients (38 men, 12
      women; mean PASI 15.8) with etanercept 25 mg or 50 mg twice weekly and evaluated
      in a retrospective analysis the efficacy and safety in comparison with data from
      published trials. Additionally, we related the clinical effect to the body mass
      index (BMI), for adipose tissue is thought to have a possible role in TNF-alpha
      homeostasis. RESULTS: Based on the literature, 30% and 49% of the patients
      treated with etanercept 25 mg and 50 mg twice weekly, respectively, should have
      achieved 75% or more improvement in PASI compared with baseline (PASI 75), and
      10% and 21%, respectively, should have achieved 90% or more improvement (PASI
      90). Our data showed that 21% in the 2 x 25 mg group and 23% in the 2 x 50 mg
      group achieved PASI 75. PASI 90 was only attained in 7% of patients treated with
      2 x 25 mg and 6% of those treated with 2 x 50 mg. Contrary to our hypothesis, the
      mean initial PASI was comparable with the mean PASI mentioned in the phase II and
      III clinical trials. Although fatigue is not identified as a side-effect of
      etanercept, 10% of our patients reported fatigue as an adverse event during
      etanercept treatment. High BMI, indicating overweight or obesity, was found both
      in patients with little efficacy and in patients achieving PASI 75 or better.
      CONCLUSIONS: Use of etanercept in real practice gives impressive results, but
      these are generally less favourable than those published in clinical trial
      reports. This is probably due to the stringent conditions for reimbursement,
      which select for more treatment-resistant patients. Fatigue as a possible side
      effect of etanercept should also be an issue for further investigation. Finally,
      the BMI does not seem to influence the patients' response to etanercept, although
      further investigations would be needed to confirm this.

PMID- 16965433
TI  - Unusual histopathological features of cutaneous leishmaniasis identified by
      polymerase chain reaction specific for Leishmania on paraffin-embedded skin
      biopsies.
AB  - BACKGROUND: Cutaneous leishmaniasis (CL) is rare in Northern Europe and may be
      overlooked because colleagues have little experience with it. OBJECTIVES: To
      identify manifestations of CL that may escape diagnosis. METHODS: Correlation of
      clinical diagnosis and histopathological findings in 28 biopsy specimens taken
      from 19 patients with CL confirmed by polymerase chain reaction (PCR) specific
      for Leishmania. RESULTS: In only one patient was the clinical diagnosis CL; other
      diagnoses included: malignant epithelial neoplasms (5), follicular cyst (2),
      atypical mycobacteriosis (1), sarcoidosis (2) and lymphoma (1). Lesions were
      single (15) or few (4) nodules predominantly situated on the extremities or face
      (16). Histopathological findings were diagnostic of CL in only 10 cases. In nine
      cases Leishmania was not identified microscopically; histopathological diagnoses
      were: granulomatous dermatitis (6), lupoid rosacea (1), foreign body granuloma
      (1) and granuloma annulare (1). Unaltered epidermis (9), nodular infiltrates (5),
      numerous multinucleated histiocytes (3), palisaded granulomas with fibrinoid
      centres (2), sarcoidal granulomas (4) and elastophagocytosis (1) misled the
      histopathologists in these cases. CONCLUSIONS: CL seems often to be misdiagnosed
      clinically in countries where it is not endemic. Histopathologically, CL may be
      misinterpreted as sarcoidosis, foreign body granuloma, lupoid rosacea and
      granuloma annulare, especially when Leishmania is not seen microscopically. We
      suggest that in Northern Europe, PCR for Leishmania-specific DNA should be
      performed routinely in any granulomatous dermatitis presenting as a single or few
      nodules on the extremities or face, even when a diagnosis of CL was not
      considered by the referring clinician.

PMID- 16965434
TI  - Bullous pemphigoid triggered by influenza vaccination? Ecological study in
      Galicia, Spain.
AB  - BACKGROUND: Influenza vaccination has been suggested to be a trigger for bullous
      pemphigoid (BP). In our area most new patients with BP are admitted to hospital.
      OBJECTIVES: To detect a difference in the rate of admissions to hospital for BP
      during population influenza vaccination programmes, which are mainly targeted at
      individuals aged 65 years or older, start in the last week of September and last
      for 2 months. METHODS: An ecological study in Galicia, north-west Spain (1997
      2005), restricted to people aged 65 years or older. Using Poisson regression,
      results were controlled for mean age of admission and percentage of the
      population vaccinated each year. RESULTS: There were 29 admissions registered
      during 'vaccination periods' (i.e. approximately 10 weeks per year, including the
      period of vaccination and two further weeks), and 158 during nonvaccination
      periods (the rest of the year). The incidence rate ratio of admissions for BP in
      vaccination vs. nonvaccination periods was 0.85 (95% confidence interval 0.57
      1.27, P = 0.43). CONCLUSIONS: Our data do not support the hypothesis of influenza
      vaccination being an important trigger for severe BP on a population level.

PMID- 16965435
TI  - Platelet-derived growth factor receptor-alpha-associated hypereosinophilic
      syndrome and lymphomatoid papulosis.
AB  - Fip1-like 1/platelet-derived growth factor receptor-alpha (FIP1L1/PDGFRA)
      positive hypereosinophilic syndrome is a rare disorder with a poor prognosis if
      untreated and for which treatment with imatinib mesilate is highly effective. A
      33-year-old man presented with recurrent papular skin lesions and marked
      peripheral eosinophilia. Skin biopsy revealed proliferation of CD30(+) T cells
      consistent with lymphomatoid papulosis (LyP), whereas molecular analysis of
      peripheral blood mononuclear cells demonstrated the presence of the FIP1L1/PDGFRA
      fusion gene. As the presence of this gene has important prognostic and
      therapeutic implications, this report underscores the importance of molecular
      testing in the evaluation of patients with LyP and peripheral eosinophilia.

PMID- 16965436
TI  - Schnitzler syndrome associated with systemic marginal zone B-cell lymphoma.
AB  - Schnitzler syndrome is a rare condition defined by chronic urticaria and
      monoclonal IgM gammopathy. Malignant evolution to Waldenstrom disease (WD) has
      been reported in several cases. We report a 49-year-old man who developed a
      marginal zone B-cell lymphoma (MZL) 3 years after the beginning of Schnitzler
      syndrome. This is the first report of MZL in association with Schnitzler
      syndrome. IgM gammopathy is a clue for the diagnosis of Schnitzler syndrome. This
      condition needs to be closely monitored; it can precede the onset of an authentic
      lymphoproliferative disorder including WD and rarely MZL.

PMID- 16965437
TI  - Atypical cutaneous leishmaniasis in two patients receiving low-dose methotrexate.
AB  - Cutaneous leishmaniasis is a protozoan disease that has high morbidity. There
      have been increasing reports of leishmaniasis in patients with an underlying
      immunosuppressed state. We present two cases of cutaneous leishmaniasis caused by
      Old World species in patients on methotrexate therapy. We postulate that the T
      cell-mediated response to leishmaniasis infection could be modulated by
      methotrexate and may render an immunosuppressed individual more susceptible to
      developing clinical disease.

PMID- 16965438
TI  - Glycine substitution mutations by different amino acids at the same codon in
      COL7A1 cause different modes of dystrophic epidermolysis bullosa inheritance.

PMID- 16965439
TI  - A case of recessive dystrophic epidermolysis bullosa caused by compound
      heterozygous mutations in the COL7A1 gene.

PMID- 16965440
TI  - Delusional parasitosis presenting as folie a trois: successful treatment with
      risperidone.

PMID- 16965441
TI  - Increased mortality in toxic epidermal necrolysis with thalidomide: corroborating
      or exonerating the pathogenetic role of TNF-alpha?

PMID- 16965442
TI  - Fumaric acid esters for severe psoriasis: the Leicestershire experience.

PMID- 16965443
TI  - Connexin 30, a new marker of hyperproliferative epidermis.

PMID- 16965444
TI  - Infliximab- and methotrexate-resistant rebound of psoriasis after discontinuation
      of efalizumab (Raptiva).

PMID- 16965445
TI  - Parthenium contact sensitivity travels to the UK.

PMID- 16965446
TI  - Development of oil cysts after subcutaneous injection of interferon-alpha and
      interleukin-2.

PMID- 16965447
TI  - Methylenetetrahydrofolate reductase polymorphism associated with moderate
      hyperhomocysteinaemia in a patient with livedo vasculopathy: treatment with
      vitamin supplementation and low molecular weight heparin.

PMID- 16965448
TI  - The PRIDE (Papulopustules and/or paronychia, Regulatory abnormalities of hair
      growth, Itching, and Dryness due to Epidermal growth factor receptor inhibitors)
      syndrome.

PMID- 16965449
TI  - Can pemphigoid be provoked by lisinopril?

PMID- 16965450
TI  - Failure of topical 0.1% alitretinoin gel for classic Kaposi sarcoma: first
      European experience.

PMID- 16965451
TI  - Malignant melanoma in renal transplant recipients.

PMID- 16965452
TI  - CD10 is expressed in dermal sheath cells of the hair follicles in human scalp.

PMID- 16965453
TI  - Focal hyperhidrosis of the anal fold: a simple technique for diagnosis and
      evaluation of therapy.

PMID- 16965454
TI  - Milia complicating successfully treated cutaneous leishmaniasis in three
      children.

PMID- 16965455
TI  - Methotrexate treatment in cutaneous lupus erythematosus: subcutaneous application
      is as effective as intravenous administration.

PMID- 16965463
TI  - Impact factors and relevance of research outputs: one step forward, two back?

PMID- 16965464
TI  - Constraints and blocks to change and improvement on acute psychiatric wards-
      lessons from the City Nurses project.
AB  - Recent years have seen sustained criticism and inspection of acute inpatient
      psychiatric wards, with the publication of reports and research leading to policy
      developments and a variety of efforts to improve perceived deficits. The City
      Nurses project seeks to reduce levels of conflict and containment on acute wards
      through the placement of expert nurses on wards to assist with the implementation
      of changes according to a working model of conflict and containment generation,
      based on previous research. Evaluation has shown significant decreases in
      aggression, absconding and self-harm by patients. However, in the course of
      working with the wards, various constraints and blocks to change have been
      identified and we describe these in detail in this paper. Analysis of the
      fieldwork diaries of the two City Nurses identified that change was hindered by
      limited staffing resources, problems with the physical environment and other
      resources, insufficient beds and the process of bed management, hierarchical
      ambiguity and multidisciplinary issues, the overdemanding role of the ward
      manager, and pervasive anxiety about the potential for serious untoward incidents
      and their implications for staff. We argue that sustained positive change in
      acute inpatient psychiatry requires these underlying structural issues to be both
      acknowledged and, if possible, resolved.

PMID- 16965465
TI  - Self-esteem and self-acceptance: an examination into their relationship and their
      effect on psychological health.
AB  - Nurses are increasingly using cognitive behaviour therapy as an intervention for
      psychological problems attached to a variety of clinical conditions. Developing
      both self-acceptance and self-esteem have been identified as ways to enhance
      cognitive interventions. However, there are disagreements about the relationship
      between self-esteem and self-acceptance and their influence on psychological
      health. The study examined the relationship between these concepts and also the
      association between the concepts and psychological health. Fifty-eight
      participants with a diagnosis of severe and enduring mental health problems were
      assessed recording levels of self-esteem, self-acceptance, depression, anxiety
      and psychological well-being. The results revealed that, in comparison with the
      general population, the sample were more likely to have lower self-acceptance and
      self-esteem, and higher levels of anxiety, depression and psychological ill
      health. The concepts of self-esteem and self-acceptance were found to be similar
      but not synonymous. Self-esteem was more closely associated with affect, with
      higher levels of self-esteem being indicative of lower levels of depression. Self
      acceptance appeared to be more closely associated with general psychological well
      being and to be more helpful when undertaking clinical work for general
      psychological problems.

PMID- 16965466
TI  - Peer support relationships: an unexplored interpersonal process in mental health.
AB  - Consumer-survivors (C/Ss) identify peer support as a resource that facilitates
      their recovery. However, little is known about the factors that influence or how
      the peer support relationship (PSR) develops/deteriorates. The purpose of the
      study was to explore and describe the PSR within the subculture of mental health.
      Using an ethnonursing method, the study focused on informants from two C/S
      organizations who received peer support (n = 14). Findings revealed that the PSRs
      may develop or deteriorate through three, overlapping phases. Contextual factors
      that influenced the development/deterioration of the PSR are discussed.
      Understanding the processes and factors that contribute to the
      development/deterioration of PSRs will enable clinicians and C/Ss to assess and
      promote the development of healthy, supportive PSRs in mental health.

PMID- 16965467
TI  - Parents' experiences of collaboration with community healthcare professionals.
AB  - Over the last decades there has been a reduction in the number of institutional
      beds in psychiatric care in Norway. This has led to more psychiatric patients
      being dependent on community care and consequently an increased need for
      collaboration with the parents of these patients. In most cases parents are an
      important source of support in helping patients manage their everyday life. The
      aim of this study was to explore how parents of adult psychiatric patients
      experience collaboration with health professionals in the community healthcare
      services. The data collection in this study is based on 12 interviews with six
      parents, and a qualitative analysis method was employed. Four themes emerged: (1)
      communication and relationship between parents and health professionals; (2) lack
      of information; (3) parents' participation in the treatment of their son or
      daughter; and (4) the need for guidance and support. It was reported that health
      professionals are suspicious of parental involvement and often refuse to allow
      them to participate in the care. Further research on parents' experiences of
      collaboration is necessary. The value of parents as an important source of
      support can be enhanced by means of increased collaboration.

PMID- 16965468
TI  - The patient's view of need and caregiving consequences: a cross-sectional study
      of inpatients with severe mental illness.
AB  - This cross-sectional study was conducted across inpatient facilities of a
      metropolitan mental health service in Sydney, Australia. Given shorter lengths of
      stay in acute inpatient facilities, it is important to ascertain differences
      between patients' and carers' perceptions of need and support in order to guide
      delivery of care in the community. The objectives were to: (1) assess the needs
      of patients recently admitted to hospital and ascertain the level of carer
      involvement while in hospital; (2) compare the degree of agreement between
      patients' and carers' perceptions of need and caregiver burden; and (3) determine
      the relationship between levels of need and carer burden prior to
      hospitalization. Over a 2-month period, consecutive patients (n = 200) were
      interviewed using the Camberwell Assessment of Need Short Appraisal Schedule and
      a modified version of the Involvement Evaluation Questionnaire to assess basic
      needs and patient perceptions of caregiver burden, respectively. Of the 200
      patients interviewed, 68% (n = 135) identified a carer. Patients with
      schizophrenia had most met needs, those with affective disorders had most unmet
      needs and patients with other diagnoses recorded the lowest number of needs
      overall. The level of agreement between patient and carer perceptions of need was
      low, possibly because of confusion about the definition of need or different
      views about the support required to fulfil a need. Patients underestimated the
      consequences of caregiving, especially the impact of strained atmosphere, global
      burden, worrying about their future and encouragement to undertake an activity,
      indicating that carers were more burdened than patients perceived them to be.

PMID- 16965470
TI  - Relating with professionals.
AB  - This paper addresses my difficulties as a carer in engaging with many
      professionals in mental health, both locally associated with my son's acute
      inpatient care, and nationally where policies are being developed and their
      implementation is pursued. All of us are affected by The Department of Health
      (DoH) Mental Health policies and their implementation by professionals has formed
      the way in which professionals relate with my son and myself. The way in which my
      son is impacted inextricably affects the way I relate to professionals. I think
      my difficulty in engaging lies in the relationships we all have with each
      another. In focusing on the process within our relationships, I attempt to raise
      professionals' awareness of what constitutes a relationship when we dialogue. As
      it takes two to engage in a dialogue, I perceive my difficulty is also the
      difficulty of the professionals. Carers are becoming increasingly involved in the
      training of mental health professionals and our combined difficulty needs to be
      resolved, so that we all benefit. In order to achieve positive progression, there
      needs to be a radical change within our relationship to provide ease of
      engagement from all parties. In this paper I tentatively suggest how this process
      can be achieved.

PMID- 16965469
TI  - Managing aggression in a psychiatric hospital using a behaviour plan: a case
      study.
AB  - This paper focuses on the critical role of nursing in implementing a behaviour
      plan in a psychiatric hospital. The plan was implemented with a 40-year-old man
      with a long history of aggression towards others and self. The study used a
      single-subject research design with baseline and intervention phases (AB Design).
      Data were collected on (1) frequency of incidents of aggression towards others
      and self; (2) use of restrictive interventions to manage aggression (i.e.
      restraints, pro re nata medication, 1:1 special observation); and (3) frequency
      of staff injury. The data show a decrease in frequency of aggression towards
      others and self, a concurrent reduction in the use of restrictive interventions
      to manage aggression, and a decrease in incidents of staff injury. The behaviour
      plan helped staff maintain a safe and therapeutic milieu. The behaviour plan has
      given the patient an opportunity to learn positive replacement behaviours and
      skills, and the opportunity eventually to leave the hospital to live in a less
      restrictive community home.

PMID- 16965471
TI  - An analysis of nurses' post-incident manual restraint reports.
AB  - Manual restraint techniques are associated with the management of violence in
      psychiatric settings. Restraint effectiveness and acceptability are under
      scrutiny, yet the nature and frequency of who or what were involved in restraint
      episodes have not previously been fully described or understood. The aim of this
      study was to describe the nature and frequency of manual restraint-related events
      and their components. This study was carried out using content analyses of
      nurses' post-incident reports from a psychiatric unit situated within a general
      hospital, and from its associated medium-secure unit. Requests for restraint
      occurred at the rate of about once per day, and the majority related to patients'
      ill-directed frustration, resistance to containment and their desire to leave the
      ward. Only half of responses to conflicts resulted in restraint implementation.
      The majority of restraint activities occurred during the afternoon and night.
      Male patients and detained patients were more frequent participants in restraint
      interventions. To a lesser extent, police, ambulance, fire services, hospital
      security, visitors and ex-patients were also involved in restraint episodes.
      Injuries were rare. In conclusion, training in restraint skills, clinical audit
      of adverse incidents, and research into psychiatric aggression all need to take
      into account the association of restraint with the enforcement of detention and
      treatment of acutely ill patients. The coupling of restraint with medication
      requires examination of its safety and efficacy. Interagency training may enable
      the essential services involved to coordinate restraint activities more
      effectively.

PMID- 16965472
TI  - How newly qualified mental health nurses perceive their role.
AB  - This paper reports a follow-up study of 11 mental health nurses (MHNs) (from an
      original of 14) who were interviewed about their perception of the role of the
      MHN while they were still mental health student nurses (MHSNs). These
      participants perceived the MHN to perform a variety of roles, implementing ward
      administration, offering physical and psychological interventions, administering
      drugs and teaching. However, some MHNs were reported to function outside the
      boundary of professional practice in the form of alleged malpractice, non
      involvement or negative approach to care. This study addresses the research
      question: 'how is the role of the MHN perceived after MHSNs have made the
      transition to MHN?'. The aim of the study is to examine whether nurses have
      changed the perception of their role having had 6-month post-registration
      experience. This information will inform the training of MHNs and identify
      possible problems with the way in which the function of the mental health nurse
      is organized. Semi-structured interviews were conducted with 11 MHNs at least 6
      months post registration. Transcripts were analysed using a qualitative approach
      based on grounded theory. Analysis of the interviews with post-registration MHNs
      produced four main themes: transition, role ambiguity, lack of support and a
      theory-practice gap. Our conclusion is that there was no drastic change to
      participants' pre- and post-registration perception in that the role of the MHN
      is ambiguous by virtue of their engagement in a variety of tasks. However, post
      registration participants were more able to articulate rationales for their role
      vis-a-vis the practical realities of the clinical areas.

PMID- 16965473
TI  - Patients' feelings about ward nursing regimes and involvement in rule
      construction.
AB  - This study compared two acute psychiatric ward nursing regimes, focusing on ward
      rules as a means of investigating the relationship between the
      flexibility/inflexibility of the regimes and patient outcomes. Previous studies
      identified an association between ward rules and patient aggression. A link
      between absconding and nurses' attitudes towards rule enforcement has also been
      explored. However, an in-depth exploration of ward rules from the perspective of
      nurses and patients had not been undertaken previously. The study aimed to
      discover the content of rules within acute psychiatric wards; to explore
      patients' responses to the rules; to evaluate the impact of rules and rule
      enforcement on nurse-patient relationships and on ward events; and to investigate
      the relationship between ward rules, ward atmosphere and ward design. The
      relevance of sociological theory emerged from the data analysis. During this
      process, the results were moved up to another conceptual level to represent the
      meaning of lived experience at the level of theory. For example, nurses'
      descriptions of their feelings in relation to rule enforcement were merged as
      role ambivalence. This concept was supported by examples from the transcripts.
      Other possible explanations for the data and the connections between them were
      checked by returning to each text unit in the cluster and ensuring that it fitted
      with the emergent theory. The design centred on a comparative interview study of
      30 patients and 30 nurses within two acute psychiatric wards in different
      hospitals. Non-participant observations provided a context for the interview
      data. Measures of the Ward Atmosphere Scale, the Hospital-Hostel Practices
      Profile, ward incidents and levels of as required (PRN) medication were obtained.
      The analysis of the quantitative data was assisted by spss, and the qualitative
      analysis by QSR *NUDIST. Thematic and interpretative phenomenological methods
      were used in the analysis of the qualitative data. A series of 11 interrelated
      concepts emerged from an analysis of the data, and a synthesis of the main
      themes. This paper focuses on the results and recommendations that emerged from
      the quantitative and qualitative patient data. A further paper will focus on
      nurses' perceptions of the same topics.

PMID- 16965474
TI  - Integrating science, practice and reflexivity--cognitive therapy with driving
      phobia.
AB  - The scientist-practitioner model has long been espoused within cognitive
      behavioural psychotherapy. The study includes an evaluation of the efficacy of
      cognitive therapy for driving phobia. Assessment, formulation and practical
      treatment of this common problem are also reported. Self-report measures
      evaluated results. Eight of the 10 consecutive cases improved significantly and
      reported that the intervention was acceptable. A reflexive analysis of the
      research findings and the influences on the first author's practice as a
      researcher and practitioner are also explored. Recommendations for future
      research are also made.

PMID- 16965475
TI  - A survey of mental health nurses' experiences of stalking.
AB  - Although an increasing amount of literature has appeared in recent years on the
      subject of stalking, little is known about mental health nurses' (MHNs)
      experiences of this phenomenon. The aims of the study were to investigate: (1)
      the incidence of stalking among a sample of MHNs in the UK; (2) who the
      perpetrators were; (3) the impact of stalking on MHNs; and (4) how MHNs manage
      their experiences. Employing a survey design, the British version of the Rutgers
      Penn clinicians and stalking questionnaire was distributed to a convenience
      sample of 400 MHNs in the UK. Data were analysed by means of descriptive
      statistics and McNemar test. The findings reveal that: (1) 50% (n = 56) of MHNs
      who completed the questionnaire had been stalked; (2) on the whole, victims were
      female (78.6%) and stalkers males (82.1%); (3) stalkers were from a variety of
      social groups including mental health service users and MHNs; (4) victims were
      threatened, followed, physically assaulted and received unwanted communication;
      (5) MHNs reported a variety of stress-related (psychological and behavioural)
      responses to their experiences; and (6) employed a range of coping strategies.
      This study serves to raise awareness of a number of issues surrounding an under
      reported phenomenon in mental health nursing and points to the need for further
      research to explore the reliability and consequences of the findings.

PMID- 16965476
TI  - Should service user involvement be consigned to history? A critical realist
      perspective.
AB  - Service user involvement in the UK healthcare agenda is now widely expected.
      Historically, service user groups have been increasingly successful in their
      demands for greater involvement. Hierarchies of involvement exist that include
      consultation and partnership working. Psychiatry is an archetypal arena in terms
      of power and control. The traditional view of interpreting the place of service
      users within this arena is that the service user is at the bottom of this
      hierarchy; involvement allows transcendence of the power hierarchy. Critical
      realist theory is offered as an alternative approach to understanding these
      complex relationships. It is argued that contemporary models of involvement
      perpetuate and sustain the power positions of the dominant discourse within
      psychiatry. It is suggested that a critical realism perspective, offers a model
      that does not kowtow to the dominant discourse but rather recognizes that service
      users now possess power, especially in terms of being able to provide services
      that statutory services providers now require. Is it time for service users to
      call the tune, and, in doing so, establish a power position outside the
      traditional hierarchy of power?

PMID- 16965477
TI  - Changing the mental health system--a survivor's view.

PMID- 16965478
TI  - Introduction of routine outcome measures: staff reactions and issues for
      consideration.
AB  - The aim of this study was to explore clinician reactions to (i) the introduction
      of routine outcome measures and (ii) the utility of outcomes data in clinical
      practice. Focus group discussions (n = 34) were conducted with mental health
      staff (n = 324) at approximately 8 months post implementation of routine outcome
      measures. A semi-structured interview schedule was used to collect data on two
      key issues; reactions to the introduction of outcome measures and factors
      influencing the utility of outcomes data in clinical practice. Data from the
      discussion groups were analysed using content analysis to isolate emerging
      themes. While the majority of participants endorsed the collection and
      utilization of outcomes data, many raised questions about the merits of the
      initiative. Ambivalence, competing work demands, lack of support from senior
      medical staff, questionable evidence to support the use of outcome measures, and
      fear of how outcomes data might be used emerged as key issues. At 8 months post
      implementation a significant number of clinical staff remained ambivalent about
      the benefits of outcome measurement and had not engaged in the process. The shift
      to a service model driven by outcomes and case-mix data will take time and
      resources to achieve. Implications for nursing staff are discussed.

PMID- 16965479
TI  - Limit setting in mental health: historical factors and suggestions as to its
      rationale.
AB  - The task of enforcing behavioural limits in mental health settings is widely
      regarded as necessary but also potentially counter-therapeutic. There has been
      little discussion of the ideological basis for limit setting in psychiatry, and
      this paper attempts to locate the progress of this ideology from the moral
      treatment movement to contemporary medicalized psychiatry. It is suggested that
      limit setting has its foundations in the Enlightenment tradition of the
      autonomous individual and the power of reason, and in the dual functions of
      psychiatry as a therapeutic and social control system. The account draws on the
      work of critical psychiatry, as well as on recent research concerning the
      discourses and practices of mental health nurses, and concludes that these dual
      functions are inherent to the psychiatric project.

PMID- 16965480
TI  - The principles and processes of inspiring hope in bereavement counselling: a
      modified grounded theory study--part one.
AB  - The concept of hope has received attention within nursing and healthcare
      literature of late yet it is fair to say that despite this increased interest,
      considerable gaps remain in our substantive knowledge base. Particularly
      noticeable is the paucity of empirically derived theory regarding the principles
      of inspiring and instilling hope in certain client groups and with persons
      enduring certain experiences. Accordingly, this two-part paper attempts to bridge
      one of these gaps by answering the question: do bereavement counsellors inspire
      hope in their clients and if so, how? Using a modified grounded theory method
      data were collected by means of semi-structured interviews; undertaken with a
      theoretical sample of bereavement counsellors and ex-clients who had received
      bereavement counselling. In keeping with the tenets of grounded theory, the data
      were coded and analysed using the constant comparison method, and this produced
      an emerging, substantive theory of the principles and processes of hope
      inspiration for this client group. This theory is comprised of a core variable:
      the implicit projection of hope and hopefulness, and three sub-core variables:
      forging the connection and the relationship; facilitating a cathartic release;
      and experiencing a healthy (good) ending. Given that the details of the core
      variable have been published previously, part one of this paper deals with a
      review of the literature and focuses on stage one; highlighting each of the
      individual categories. Where as part two focuses on stages two and three, again
      highlights the categories therein and offers a discussion and conclusion.

PMID- 16965481
TI  - The principles and processes of inspiring hope in bereavement counselling: a
      modified grounded theory study--part two.
AB  - This second part of a two-part paper attempts to answer the question: do
      bereavement counsellors inspire hope in their clients and if so, how? Using a
      modified grounded theory method data were collected by means of semi-structured
      interviews; undertaken with a theoretical sample of bereavement counsellors and
      ex-clients who had received bereavement counselling. In keeping with the tenets
      of grounded theory, the data were coded and analysed using the constant
      comparison method, and this produced an emerging, substantive theory of the
      principles and processes of hope inspiration for this client group. This theory
      is comprised of a core variable: the implicit projection of hope and hopefulness,
      and three sub-core variables: forging the connection and the relationship;
      facilitating a cathartic release; and experiencing a healthy (good) ending. Part
      one of this paper included a review of the literature and focused on stage one.
      Part two on the other hand, focuses on stages two and three, and highlights the
      categories therein. The paper concludes by highlighting implications arising from
      the findings (other discussion points have been published elsewhere).

PMID- 16965482
TI  - Aggressive behaviour by people with dementia in residential care settings: a
      review.
AB  - This paper considers the phenomenon of aggressive behaviour perpetrated by people
      with dementia in residential care settings. Aggressive behaviour is defined in
      the context of people with dementia, and the problem of ascertaining the
      incidence of aggression among people with dementia is discussed. The emotional
      impact of assaults on nurses and other professionals is highlighted, and
      differing perspectives on the causation of aggressive behaviour are considered.
      Management strategies derived from the physical/pharmacological; environment
      management; behaviour modification and person-centred approaches are reviewed.
      Our conclusion is that while certain strategies appear to reflect good and common
      sense practice, in particular those deriving from the person-centred approach,
      there is no clear research evidence for the general effectiveness of any one
      management approach, and each has drawbacks of a practical or ethical nature.
      There is also little empirical information about how professional carers actually
      manage aggressive behaviour in practice.

PMID- 16965483
TI  - Post-psychiatry: good ideas, bad language and getting out of the box.

PMID- 16965484
TI  - Perceived facilitators and barriers to the implementation of an advanced
      practice: nursing intervention for HIV regimen adherence among the seriously
      mentally ill.

PMID- 16965487
TI  - Rhegmatogenous retinal detachment: are we making progress?

PMID- 16965488
TI  - Macular recovery after retinal detachment.
AB  - Macular recovery after surgery for retinal detachment (RD) depends on
      preoperative and postoperative predictive factors. Preoperative visual acuity is
      the main preoperative factor correlating positively with good macular recovery.
      Preoperative factors, which influence macular recovery negatively, include
      duration of macular detachment, height of macular detachment and vitreomacular
      traction. Postoperative factors, which influence macular recovery negatively,
      include cystoid macular oedema, epiretinal membranes, retinal folds, subretinal
      retinal pigment epithelium (RPE) migration and persistent subretinal fluid on
      optical coherence tomography (OCT). According to the latest available data, a
      detached macula has to be reattached within 5 days to optimize functional
      recovery. However, new therapeutic options such as exposure to hyperoxia or
      different growth factors may help to improve the final visual outcome in the
      presence of an already detached macula.

PMID- 16965489
TI  - An evidence-based analysis of surgical interventions for uncomplicated
      rhegmatogenous retinal detachment.
AB  - PURPOSE: To evaluate the various surgical interventions available for
      uncomplicated rhegmatogenous retinal detachment. METHODS: Reports of controlled
      clinical trials of surgical interventions (pneumatic retinopexy, scleral buckling
      and vitrectomy) for uncomplicated rhegmatogenous retinal detachment indexed in
      MEDLINE from 1968 to January 2006 were included. The primary outcomes evaluated
      included single-operation reattachment rates, multiple reoperation reattachment
      rates and improvements in visual acuity (VA). RESULTS: We found five controlled
      trials (two randomized) comparing the efficacy of pneumatic retinopexy versus
      scleral buckling. The single-operation reattachment rates were higher for scleral
      buckling, but the final reattachment rates were similar. We found nine controlled
      trials (four randomized) evaluating vitrectomy. There were no statistically
      significant differences between retinal reattachment rates or final visual
      acuities, except in one randomized and one non-randomized controlled trial in
      which the VAs were significantly better in the vitrectomy than the scleral
      buckling group. CONCLUSIONS: Pneumatic retinopexy is a possible alternative to
      scleral buckling in the treatment of uncomplicated rhegmatogenous retinal
      detachment. The rates of missed or new retinal breaks after pneumatic retinopexy,
      however, are higher than following scleral buckling. The clinical outcomes of
      vitrectomy for rhegmatogenous retinal detachment compare favourably.

PMID- 16965490
TI  - Longterm incidence of rhegmatogenous retinal detachment and survival in a defined
      population undergoing standardized phacoemulsification surgery.
AB  - PURPOSE: To determine the longterm risk of pseudophakic retinal detachment (PRD)
      in a defined population undergoing standardized phacoemulsification surgery at a
      single centre. DESIGN: We carried out a register-based, retrospective,
      consecutive, uncontrolled study. All 6352 eyes that underwent cataract surgery at
      our institution during the years 1996-1998 were included in the study. The main
      outcome measure was the incidence of surgery for PRD. METHODS: Cataract-operated
      eyes were identified by a search in the local hospital registry. Eyes that
      subsequently underwent surgery for PRD were identified by a search in the Danish
      Patients Registry (LPR). Follow-up ended by 31 December 2003. Eyes in patients
      who died before that date were censored. RESULTS: The 8-year cumulated incidence
      of PRD after phacoemulsification was 0.93 per eye (95% CI 0.65-1.33). This is
      8.77 (95% CI 7.12-10.72) times higher than expected in eyes that do not undergo
      cataract surgery. The incidence rate for retinal detachment was significantly
      higher in pseudophakic eyes than in the background population for at least 6
      years after surgery. Patient mortality was slightly increased for men, but no
      different for women from that of the background population. CONCLUSION: For eyes
      undergoing phacoemulsification surgery, the cumulated incidence of PRD continues
      to increase for at least 8 years after surgery. Comparison of the cumulated
      incidence of PRD between different studies requires equal lengths of follow-up.

PMID- 16965491
TI  - The relationships between risk factors and the distribution of retinopathy
      lesions in type 2 diabetes.
AB  - PURPOSE: Previous studies have shown that the progression of diabetic retinopathy
      to vision-threatening lesions may be related to the development of retinopathy
      lesions in specific retinal areas. The purpose of the present study was to
      examine whether the occurrence of retinopathy in these retinal areas is related
      to known risk factors for progression of retinopathy in type 2 diabetes. METHODS:
      A total of 377 randomly selected patients with type 2 diabetes underwent
      examinations which included measurement of blood pressure, haemoglobin A1c and
      cholesterol, and a full eye examination including fundus photography. The fundus
      photographs were digitized and a computer-assisted technique was used to quantify
      retinopathy lesions in the macular area, around the vascular arcades and in the
      retinal periphery. Only the number of microaneurysms/haemorrhages was sufficient
      for statistical analysis. RESULTS: Patients with retinopathy had significantly
      longer diabetes duration, and higher blood pressure and HgbA1c than patients
      without retinopathy. However, among the patients with retinopathy there was no
      correlation between these risk factors and the overall number of
      microaneurysms/haemorrhages or the number of these lesions in the local areas of
      the fundus studied. CONCLUSIONS: The localized distribution of retinopathy
      lesions does not correlate with known risk factors and background factors for the
      development of diabetic retinopathy in the early stages of the disease. Future
      improvements of grading systems for diabetic retinopathy should focus on a
      quantification of the overall number and dynamics of retinopathy lesions in the
      early stages of retinopathy and the regional distribution and dynamics of lesions
      in more advanced stages of retinopathy.

PMID- 16965492
TI  - Intravitreal triamcinolone acetonide for diffuse diabetic macular oedema: 6-month
      results of a prospective controlled trial.
AB  - PURPOSE: To evaluate prospectively the efficacy and safety of one intravitreal
      injection of 4 mg triamcinolone acetonide for refractory diffuse diabetic macular
      edema. METHODS: Seventeen patients with bilateral diabetic macular edema
      unresponsive to laser photocoagulation. In all patients, one eye was injected,
      and the other served as a control. The intervention consisted in intravitreal
      injection of 4 mg triamcinolone acetonide. The main outcome measure was central
      macular thickness (CMT) at 4, 12 and 24 weeks, measured by Optical Coherence
      Tomography. Secondary outcomes were Early Treatment Diabetic Rentinopathy Study
      (ETDRS) scores, intraocular pressure and cataract PROGRESSION. RESULTS: Before
      injection, mean +/- SD CMT was 566.4 +/- 182.4 mum in injected eyes. Four, 12,
      and 24 weeks after injection, it was 228.4 +/- 47.5 mum, 210.9 +/- 87.2 mum and
      358.5 +/- 160.5 mum respectively. CMT was significantly lower in injected eyes
      vs. control eyes except 24 weeks after injection because of a recurrence of
      macular edema in 9/17 injected eyes. Mean +/- SD gain in ETDRS score was
      significantly better in injected eyes vs. control eyes 4, 12 and 24 weeks after
      TA injection. In 9 of the 17 injected eyes, intraocular pressure exceeded 24 mmHg
      and was controlled by topical medication. CONCLUSION: In the short-term,
      intravitreal injection of triamcinolone effectively reduces macular thickening
      due to diffuse diabetic macular edema and improves visual acuity in most cases.
      The long-term effect of this treatment and predictive factors of visual recovery
      remain to be elucidated.

PMID- 16965493
TI  - Ophthalmological follow-up at 2 years of age of all children previously screened
      for retinopathy of prematurity: is it worthwhile?
AB  - PURPOSE: To evaluate the extent to which ophthalmological follow-up at 2 years of
      age of children born before 32 weeks gestation identifies obvious visual
      problems, strabismus and significant ametropia (target conditions). METHODS: Of
      172 children born during a period of 2.5 years from January 2000, 142 underwent
      an ophthalmological examination at a median age of 2.33 years. This included
      evaluation of visual behaviour, cover testing and autorefractometry in
      cycloplegia. For children with the target conditions, we investigated whether the
      child had been followed in the eye clinic or referred before 2 years of age, or
      whether the abnormality was detected as a result of the follow-up examination.
      RESULTS: None of the target conditions were found in 117 children. None of four
      children with obviously abnormal visual behaviour, two of 10 children with
      strabismus and four of 11 with large refractive errors were detected in the
      follow-up examination. Thus the target conditions were detected at the follow-up
      examination in only six of 142 children (4.2%). CONCLUSIONS: Although ophthalmic
      abnormalities are common in children born prematurely, most of them are
      identified because high-risk children are followed regularly in eye clinics and
      because parents and primary health care personnel detect strabismus.
      Ophthalmological follow-up of all children born before 32 weeks appears not to be
      worthwhile and is therefore only recommended for high-risk children.

PMID- 16965494
TI  - The prevalence of age-related maculopathy (ARM) in an urban Norwegian population:
      the Oslo Macular study.
AB  - PURPOSE: To examine the prevalence of early and late age-related maculopathy
      (ARM) in citizens aged 51 years and older in the city of Oslo and its
      surroundings. METHODS: We selected a random sample of 800 subjects, using a cross
      sectional study design. A total of 459 of the 770 eligible subjects agreed to
      participate, giving an attendance rate of 59.6%. Stereoscopic colour digital
      photographs were obtained and graded at a certified reading centre using the
      International Classification Grading System for ARM. RESULTS: Early ARM in either
      eye was found in 43.1% (95% CI 38.5-47.7) of subjects aged 51 years and older.
      This was due to a much higher prevalence of pigmentary changes, predominantly
      hyperpigmentation in all age groups, than previously reported; 37.5% of people
      aged 51-60 years of age had pigmentary changes > or = 63 microm, increasing to
      66.0% in the oldest age group. In people aged 71 years and older, geographic
      atrophy (GA) was found in either eye in 3.6% (95% CI 0.4-6.8) and exudative
      macular degeneration (AMD) was found in either eye in 2.9% (95% CI 0.0-5.7) of
      subjects. CONCLUSION: To our knowledge, this is the first published study to rely
      solely on digital photography for grading purposes in a population-based study.
      Early ARM was found to have a higher prevalence than previously reported in other
      populations. Exudative AMD and GA had similar prevalences to those described in
      the literature, although the prevalence of GA tended to be higher than previously
      reported in some surveys.

PMID- 16965495
TI  - Topography of the posterior arteries supplying the eye and relations to the optic
      nerve.
AB  - PURPOSE: The aim of the study was to investigate the arterial blood supply of the
      intraorbital part of the optic nerve. METHODS: The location, course, length and
      diameter of the central retinal artery (CRA) and posterior ciliary arteries were
      studied in 19 adult white male preserved cadavers of between 35 and 75 years of
      age. RESULTS: In right eyes, the first branch of the intraorbital part of the
      ophthalmic artery was the CRA in 26.3% (5/19) and the CRA and medial posterior
      ciliary artery in 21% (4/19) of eyes. In left eyes, the first branch of the
      intraorbital part of the ophthalmic artery was the CRA in 47.4% (9/19) and the
      CRA and medial posterior ciliary artery in 26.3% (5/19) of eyes. The CRA was
      observed as a single branch in 57.9% and a trunk in 42.1% of right eyes, and as a
      single branch in 52.6% and a trunk in 47.3% of left eyes. The outer diameter of
      the CRA measured 0.6 +/- 0.1 mm (min-max 0.5-0.9 mm) in right eyes and 0.6 +/-
      0.2 mm (min-max 0.4-0.9 mm) in left eyes. The CRA entered the optic nerve 7.5 +/-
      2.2 mm (min-max 5.3-12.5 mm) behind the ocular bulb in right eyes and 7.4 +/- 2.3
      mm (min-max 5.3-14.1 mm) behind it in left eyes, at its lower and medial side.
      The posterior ciliary arteries ran forward, divided into multiple branches and
      pierced the sclera close to the optic nerve medially, laterally or superiorly.
      The longitudinal capillaries ran between the optic nerve and the CRA antero
      posteriorly, while the transverse capillaries surrounded the optic nerve.
      Collaterals from both the longitudinal and transverse capillaries joined to form
      a complicated capillary plexus. CONCLUSION: This article confirms the well known
      variability of the arterial circulation of the intraorbital part of the optic
      nerve. Better understanding of the arterial anatomy of the intraorbital part of
      the optic nerve should enable appropriate modification of surgical techniques.

PMID- 16965496
TI  - Comparison between GDx VCC scanning laser polarimetry and Stratus OCT optical
      coherence tomography in the diagnosis of chronic glaucoma.
AB  - PURPOSE: To compare the abilities of scanning laser polarimetry with the variable
      corneal compensator (GDx VCC) with those of optical coherence tomography (Stratus
      OCT) in discriminating between healthy and early-to-moderate perimetric
      glaucomatous eyes. METHODS: A total of 95 glaucomatous patients (mean deviation -
      3.7 +/- 3.0 dB, pattern standard deviation 4.5 +/- 2.7 dB) and 62 control
      subjects underwent imaging by the GDx VCC and Stratus OCT using both optic nerve
      head (ONH) and retinal nerve fibre layer (RNFL) scan protocols. One eye per
      patient was considered. Sensitivity at > or = 90% specificity and area under the
      receiver operating characteristic curve (AROC) were calculated for each GDx VCC
      and Stratus OCT index. RESULTS: The largest AROCs with Stratus OCT were
      associated with cup : disc area ratio (0.88) for ONH scan indices, and with
      average thickness (0.84) for RNFL scan indices. The nerve fibre indicator
      provided the greatest AROC for the GDx VCC indices (0.85). CONCLUSIONS: Both the
      GDx VCC and Stratus OCT instruments were shown to be useful in the detection of
      glaucomatous damage. The best performing indices for the GDx VCC and Stratus OCT
      with both ONH and RNFL scans gave similar AROCs, showing a moderate sensitivity
      in early-to-moderate glaucoma patients.

PMID- 16965497
TI  - Non-penetrating deep sclerectomy for glaucoma associated with Sturge-Weber
      syndrome.
AB  - PURPOSE: To report the results of non-penetrating deep sclerectomy (NPDS) in the
      treatment of glaucoma associated with Sturge-Weber syndrome (SWS). METHODS: We
      carried out a retrospective case series analysis of patients who underwent NPDS
      for glaucoma associated with SWS between 1998 and 2003. The control of glaucoma
      after NPDS, the results of surgery on intraocular pressure, the need for
      additional medical treatment and surgical complications were studied. RESULTS:
      Twelve eyes of nine patients, aged 11 days to 24 years, underwent filtering
      surgery: nine NPDS procedures were performed and three surgical procedures had to
      be converted to trabeculectomy because NPDS was not technically achievable. The
      mean follow-up after surgery was 26.3 months (range 6-48 months). Two
      trabeculectomies were complicated by choroidal effusion, which resolved in both
      cases. Good control of glaucoma was obtained during follow-up. CONCLUSIONS: Non
      penetrating deep sclerectomy is transiently efficient in the treatment of SWS
      associated glaucoma. Further studies of NPDS for the treatment of glaucoma
      associated with SWS are warranted.

PMID- 16965498
TI  - Photodynamic treatment in a rabbit model of glaucoma surgery.
AB  - PURPOSE: To evaluate the safety and efficacy of postoperative verteporfin
      photodynamic treatment as an adjunct to glaucoma experimental filtration surgery
      in rabbits. METHODS: Dutch belted (n = 15) rabbits underwent full thickness
      sclerectomy in one eye. The experimental group (group 1, n = 7) underwent i.v.
      injection of verteporfin and subsequent photoactivation at the operative site on
      postoperative day 1 (POD 1). Control groups of animals received either light
      exposure (group 2, n = 4) or verteporfin (group 3, n = 2), or no intervention
      (group 4, n = 2). Intraocular pressure (IOP) was measured prior to the procedure
      (POD 0) and daily thereafter for the first week after sclerectomy (PODs 1-7) and
      every other day for the second week (PODs 9, 11, 13, 15). Percentage IOP
      reductions of operated over contralateral control eyes were compared among the
      various groups. Success rates (percentage IOP reduction > 15%) were also compared
      between the experimental and control groups. Eyes were histologically examined
      for evaluation of fibrosis. RESULTS: Rabbits in the experimental group (group 1)
      had a mean +/- SEM percentage IOP reduction of 25 +/- 3% during the follow-up
      period. In contrast, groups 2, 3 and 4 had IOP reductions of 4 +/- 5%, 12 +/- 7%
      and 4 +/- 6%, respectively (p < 0.005, anova among all four groups). Successful
      IOP reduction (> or = 15%) over the contralateral eye at POD 15 was achieved in
      six of seven experimental animals, but only in one of eight control animals (p <
      0.02, chi-squared test). Bleb failure occurred significantly earlier in the
      control eyes compared with eyes receiving PDT (p < 0.003, log rank test). Blebs
      in the experimental group differed from those in the control groups
      histologically, lacking significant collagen deposition in the area of the
      sclerostomy. CONCLUSIONS: Wound healing in glaucoma surgery may be successfully
      modulated postoperatively using photodynamic therapy with i.v. administered
      photosensitizer.

PMID- 16965499
TI  - Posterior capsule opacification: comparisons between morphology, visual acuity
      and self-assessed visual function.
AB  - PURPOSE: To investigate whether posterior capsule opacification (PCO) morphology,
      visual acuity (VA) and self-assessed visual function correlate, and to compare
      perceived visual disabilities with those of cataract patients with corresponding
      VA. METHODS: Twenty-one patients with PCO were examined before capsulotomy. In
      adjunct to the ophthalmological examination, the patients completed a Catquest
      questionnaire and a digitized retroillumation image was acquired. The images were
      analysed with the Evaluation of Posterior Capsule Opacification (EPCO) program.
      Data for visual function were compared with data from the National Swedish
      Cataract Register (NCR). RESULTS: The epco values were correlated with VA in the
      PCO eyes: the higher the epco score, the lower the VA. There were also
      correlations between the epco scores, satisfaction with vision, and perceived
      disabilities in daily life. Symptoms of glare were not significantly correlated
      with epco scores or with VA. Visual acuity in PCO eyes was better correlated with
      perceived disabilities and satisfaction with vision than VA in eyes with
      cataract. CONCLUSIONS: There was a significant correlation between epco scores
      and VA and between epco scores and Catquest. Consequently, the morphological
      method was related to the self-assessed visual function. Patients with PCO seemed
      to have more disturbed visual function, as defined by Catquest, than cataract
      patients with the same VA.

PMID- 16965500
TI  - Refractive and visual outcome of paediatric cataract surgery in the Ukraine.
AB  - PURPOSE: To describe the refractive and visual outcomes after surgery for
      congenital or developmental cataract in the Ukraine. METHODS: Cataract surgery
      was performed in 65 children aged 3-15 years. The cataracts were bilateral in 44
      children and unilateral in 21. Examinations, including visual acuity (VA) and
      objective refraction using retinoscopy, were performed preoperatively and at 1
      day, 6 months and 2 years postoperatively. Neither occlusion therapy nor
      spectacles were prescribed. RESULTS: Almost all children (96%) gained in VA. In
      all, 40% of the bilateral cases achieved a corrected Snellen VA > or = 0.5 and
      44% of the unilateral cases obtained a corrected VA > or = 0.2. The difference
      between VA (logMAR) preoperatively and 2 years postoperatively was statistically
      significant (p < 0.05). The bilateral cases showed a postoperative reduction in
      mean astigmatism from 3.9 D (1 day postoperatively) to 0.6 D (2 years
      postoperatively) (p < 0.001), while the unilateral cases showed a reduction from
      4.2 D (1 day postoperatively) to 0.4 D (2 years postoperatively) (p < 0.001).
      CONCLUSION: Good postoperative VA was achieved in the group with bilateral
      cataract. Surprisingly, even in the group with unilateral cataract, an increase
      in VA was obtained, despite the lack of postoperative correction with glasses or
      occlusion therapy.

PMID- 16965501
TI  - Refractive error after triple and non-simultaneous procedures: is the application
      of a standard constant keratometry value in IOL power calculation advisable?
AB  - PURPOSE: The purpose of this investigation was to determine whether or not the
      use of a standard constant keratometry value in cases of preoperative abnormal
      keratometry values in biometry for triple procedures is advisable. METHODS:
      Cataract surgery and penetrating keratoplasty were performed in 82 eyes; 53 eyes
      underwent triple procedures and 29 eyes underwent non-simultaneous procedures. A
      standard constant keratometry value of 42.50 D was applied in 18 triple-procedure
      eyes because the preoperative measured keratometry values were outwith the normal
      range (41-47 D). The spherical equivalent and expected values were compared after
      a mean follow-up of 20.5 months. RESULTS: Cases in the triple-procedure group
      that achieved spherical equivalent within +/- 2.0 D of expected values included
      nine of 18 eyes (50%) in which a standard constant keratometry value of 42.50 D
      was applied, three of 17 eyes (18%) in which keratometry values outwith the
      normal range were applied (p = 0.044), and eight of 18 eyes (45%) in which
      keratometry values within the normal range were applied (p = 0.862). Cases in the
      non-simultaneous procedure group that achieved spherical equivalent within +/-
      2.0 D of expected values included 22 of 24 eyes (92%) in which keratometry values
      within the normal range were applied (p = 0.0025), and five of five eyes (100%)
      in which a standard constant keratometry value was applied. CONCLUSIONS: The
      application of a standard constant keratometry value of 42.50 D for intraocular
      lens power calculation in triple procedures can be recommended if abnormal
      keratometry values were measured previously. If possible, non-simultaneous
      procedures should take priority.

PMID- 16965502
TI  - Biochemical changes in selenite cataract model measured by high-resolution MAS H
      NMR spectroscopy.
AB  - PURPOSE: To correlate certain levels of lens opacification with high-resolution
      magic-angle spinning proton nuclear magnetic resonance (HR-MAS (1)H NMR)
      spectroscopy analysis of the biochemical changes in rat lenses in a selenite
      cataract model. METHODS: Selenite cataract was induced by injecting 13-day-old
      Sprague-Dawley rat pups with a single subcutaneous dose of sodium selenite (3.28
      mg/kg in 0.9% sodium chloride solution). Lens opacification was observed using a
      photographic slit-lamp microscope at selected time-points 3, 6 and 9 days after
      selenite injection and was then graded (levels 0, 1 and 2). The animals were
      killed after the slit-lamp microscopy, lenses were removed and HR-MAS (1)H NMR
      spectra from intact lenses were obtained. Relative changes in metabolite
      concentrations were determined after comparison with matched lenses from
      untreated animals. RESULTS: Photographic slit-lamp microscopy revealed different
      stages of cataract in all animals treated with selenite. In the high quality HR
      MAS (1)H NMR spectra of the lenses, more than 30 different metabolites were
      identified in each lens. With the exception of taurine, the concentrations of all
      amino acids showed a significant increase (p < 0.05) in the second level of
      cataract. By contrast, glutathione (GSH), succinate and phosphocholine
      concentrations were significantly reduced. CONCLUSIONS: For the first time, this
      study demonstrates the potential to correlate the level of lens opacification
      with the biochemical changes obtained with HR-MAS (1)H NMR spectroscopy analysis
      in a selenite cataract model.

PMID- 16965503
TI  - Effect of 0.03% tacrolimus ointment on conjunctival cytology in patients with
      severe atopic blepharoconjunctivitis: a retrospective study.
AB  - PURPOSE: To evaluate the efficacy and effect of tacrolimus ointment on
      conjunctival cytology in patients with atopic blepharoconjunctivitis or
      keratoconjunctivitis. METHODS: Ten patients with severe atopic
      blepharoconjunctivitis treated with 0.03% tacrolimus ointment once daily as an
      intermittent treatment were analysed retrospectively. The main outcome measures
      were clinical response to topical tacrolimus, adverse events and changes in the
      inflammatory cells obtained from conjunctival brush samples. RESULTS: Marked
      clinical responses in blepharitis and conjunctivitis symptoms were seen after a
      mean follow-up time of 6 weeks. Clinical scores decreased by 67% in blepharitis
      and 74% in conjunctivitis symptoms. No severe adverse events or signs of
      immunosuppression such as herpes simplex infections occurred. No significant
      changes occurred in visual acuity, refraction, anterior chamber, retina or
      intraocular pressure. Median decreases were 85% (p =0.01) in conjunctival
      eosinophils, 50% (p = 0.01) in neutrophils and 58% (p = 0.02) in lymphocytes.
      CONCLUSIONS: Tacrolimus ointment is potentially a safe and effective treatment
      for atopic blepharoconjunctivitis. Regular treatment of the eyelids once daily
      may also lead to clinical and cytological improvement of the conjunctivitis.

PMID- 16965504
TI  - Corneal tattooing to mask subsequent opacification after amniotic membrane
      grafting for stromal corneal ulcer.
AB  - PURPOSE: We aimed to report on the cosmetic efficacy of corneal tattooing using
      India ink for resolving corneal opacities resulting from amniotic membrane
      grafting carried out to promote corneal wound healing in stromal corneal ulcers.
      METHODS: Amniotic membrane grafting of corneal ulcers was carried out in three
      patients. After corneal re-epithelialization, a 30-gauge needle filled with India
      ink was placed into the amniotic membrane space located between the regenerated
      corneal epithelium and the stromal bed. The ink was then carefully injected.
      RESULTS: The cornea was successfully stained with India ink in all cases. There
      were no significant complications during the mean follow-up period of 17 months.
      All the patients were satisfied with the corneal staining. CONCLUSION: When a
      corneal opacity occurs after an amniotic membrane graft for stromal corneal
      ulcer, corneal tattooing by intrastromal injection of India ink into the amniotic
      membrane space may be a very useful method of achieving a good cosmetic result.

PMID- 16965505
TI  - Arteriovenous adventitial sheathotomy for branch retinal vein occlusion: report
      of a case with longterm follow-up.
AB  - PURPOSE: To report the longterm follow-up of a case of branch retinal vein
      occlusion (BRVO) treated with vitrectomy and adventitial sheathotomy. METHODS: A
      three-port vitrectomy was performed in a 55-year-old man with symptoms of BRVO of
      about 3 months' duration. After a core vitrectomy, the adventitial sheath of the
      affected arteriovenous crossing was dissected so that the anterior surface of the
      arteriole was freely exposed. RESULTS: On the second postoperative day, visual
      acuity (VA) in the affected left eye had increased from preoperative 0.3 to 0.6.
      Within 6 months the fundus had almost normalized and vision improved to 1.0.
      Cataract surgery was performed about 2 years after the vitrectomy. At a follow-up
      4 years and 11 months after the sheathotomy, VA was 1.0 and no signs of
      recurrence were seen. CONCLUSIONS: Adventitial sheathotomy may improve vision in
      selected cases of BRVO. Further studies are necessary to determine the role of
      sheathotomy in the management of cases with BRVO.

PMID- 16965506
TI  - Combined central retinal artery and vein occlusion in Churg-Strauss syndrome:
      case report.
AB  - PURPOSE: To describe a rare case of Churg-Strauss syndrome presenting with severe
      visual loss due to a combined central retinal vein and artery occlusion. METHODS:
      A 42-year old man with a medical history of asthma and blood hypereosinophilia
      developed a sudden loss of vision in his right eye. We describe the clinical
      features and evolution of the case after treatment. RESULTS: A combined occlusion
      of the central retinal artery and central retinal vein was diagnosed by the
      funduscopic appearance of retinal whitening, macular cherry-red spot,
      papilloedema, retinal haemorrhages in all four quadrants and dilated and tortuous
      veins. The diagnosis was confirmed by a fluorescein angiogram showing absence of
      retinal filling and normal choroidal filling. Churg-Strauss syndrome was
      diagnosed based on the necessary presence of four of six criteria for the disease
      proposed by the American College of Rheumatology. Corticosteroid therapy was
      initiated. However, during the following year when tapering off the daily dosage,
      the patient experienced two relapses, with pulmonary symptoms and
      hypereosinophilia, and the corticosteroid dosage had to be augmented. The patient
      presented with neovascular glaucoma 7 weeks after the vascular occlusion and
      experienced no visual improvement. CONCLUSION: Combined central retinal artery
      and vein occlusion can occur in Churg-Strauss syndrome. We suggest that regional
      vasculitis may be the pathological mechanism underlying the vascular occlusions
      observed in our case. The condition carries a very poor prognosis for vision, due
      to the resulting retinal ischaemia, and a poor general prognosis due to the late
      stage of the systemic disease. Corticosteroids should be instigated promptly in
      order to prevent further systemic or ocular vasculitis.

PMID- 16965507
TI  - Resolution of subretinal haemorrhage and fluid after intravitreal bevacizumab in
      aggressive peripapillary subretinal neovascularization.

PMID- 16965508
TI  - Repetitive preretinal haemorrhages caused by physical exertion.

PMID- 16965509
TI  - Persistence of triamcinolone acetonide following macular hole surgery.

PMID- 16965510
TI  - Malignant glaucoma as a complication of intravitreal triamcinolone acetonide.

PMID- 16965511
TI  - Intravitreal bevacizumab for occult choroidal neovascularization with pigment
      epithelium detachment in age-related macular degeneration.

PMID- 16965514
TI  - Whole genome sequencing of a novel temperate bacteriophage of P. aeruginosa:
      evidence of tRNA gene mediating integration of the phage genome into the host
      bacterial chromosome.
AB  - Whole genome sequencing of a novel Pseudomonas aeruginosa temperate bacteriophage
      PaP3 has been completed. The genome contains 45 503 bp with GC content of 52.1%,
      without more than 100 bp sequence hitting homologue in all sequenced phage
      genomes. A total of 256 open reading frames (ORFs) are found in the genome, and
      71 ORFs are predicated as coding sequence (CDS). All 71 CDS are divided into the
      two opposite direction groups, and both groups meet at the bidirectional
      terminator site locating the near middle of the genome. The genome is dsDNA with
      5'-protruded cohesive ends and cohesive sequence is 'GCCGGCCCCTTTCCGCGTTA' (20
      mer). There are four tRNA genes (tRNA(Asn), tRNA(Asp), tRNA(Tyr) and tRNA(Pro))
      clustering at the 5'-terminal of the genome. Analysis of integration site of PaP3
      in the host bacterial genome confirmed that the core sequence of
      (GGTCGTAGGTTCGAATCCTAC-21mer) locates at tRNA(Pro) gene within the attP region
      and at tRNA(Lys) gene in the attB region. The results indicated that 3'-end of
      tRNA(Pro) gene of the PaP3 genome is involved in the integration reaction and 5'
      end of tRNA(Lys) gene of host bacteria genome is hot spot of the integration.

PMID- 16965515
TI  - T-cell stimulating protein A (TspA) of Neisseria meningitidis is required for
      optimal adhesion to human cells.
AB  - T-cell stimulating protein A (TspA) is an immunogenic, T-cell and B-cell
      stimulating protein of Neisseria meningitidis. Sequence similarity between TspA
      and FimV, a Pseudomonas aeruginosa protein involved in twitching motility,
      suggested a link between TspA and type IV pili (Tfp). To determine the role of
      TspA an isogenic deletion mutant was created. Loss of TspA did not affect
      twitching motility or piliation indicating that there are functional differences
      between TspA and FimV. Mutation of tspA led to a significant reduction in
      adhesion of meningococci to meningothelial and HEp-2 cells, which was not due to
      a lack of transcription of adjacent genes or pilC1. Other Tfp-mediated phenotypes
      (i.e. auto-aggregation and transformation competence) were not altered. Our
      results indicate that the role of TspA in adhesion is unlikely to be directly
      linked to the function of Tfp. TspA was expressed by all N. meningitidis and
      Neisseria polysaccharea strains examined but not by Neisseria gonorrhoeae or
      Neisseria lactamica, although sequences with homology to tspA were present in
      their genomes. In summary, TspA is a highly conserved antigen that is required
      for optimal adhesion of meningococci to human cells.

PMID- 16965516
TI  - Dynamin is required for F-actin assembly and pedestal formation by
      enteropathogenic Escherichia coli (EPEC).
AB  - After attaching to human intestinal epithelial cells, enteropathogenic
      Escherichia coli (EPEC) induces the formation of an actin-rich pedestal-like
      structure. The signalling pathway leading to pedestal formation is initiated by
      the bacterial protein Tir, which is inserted into the host cell plasma membrane.
      The domain exposed on the cell surface binds to another bacterial protein,
      intimin, while one of the cytoplasmic domains binds the adaptor protein Nck. This
      leads to recruitment of other cytoskeletal proteins including neural Wiskott
      Aldrich syndrome protein (N-WASP) and Arp2/3, resulting in focused actin
      polymerization at the site of bacterial attachment. In this study we investigated
      the role of the large GTPase dynamin 2 (Dyn2) in pedestal formation. We found
      that in HeLa cells, both endogenous and overexpressed Dyn2 were recruited to
      sites of EPEC attachment. Recruitment of endogenous Dyn2 required the presence of
      Tir, Nck and N-WASP but was independent of cortactin and Arp2/3. Knock-down of
      Dyn2 expression by RNA interference reduced actin polymerization and pedestal
      formation. Overexpression of dominant-negative mutants of Dyn2 also reduced
      pedestal formation and prevented recruitment of N-WASP, Arp3 and cortactin, but
      not Nck. Together, our results indicate that Dyn2 is an integral component of the
      signalling cascade leading to actin polymerization in EPEC pedestals.

PMID- 16965517
TI  - Defining the Mga regulon: Comparative transcriptome analysis reveals both direct
      and indirect regulation by Mga in the group A streptococcus.
AB  - The regulator Mga in the group A streptococcus (GAS) is known to directly
      activate several virulence genes important for colonization and immune evasion.
      Transcriptome analysis comparing two mga-1 serotypes (M1 SF370, M6 JRS4) and one
      mga-2 serotype (M4 GA40634) against their isogenic mga-inactivated strains
      uncovered a broader Mga regulon profile containing both activated and repressed
      genes with predicted functions primarily related to sugar metabolism. This was
      reflected in the altered abilities of M1 and M4 Mga mutants to grow in chemically
      defined media with a single sugar source compared with their wild-type
      counterparts. Although the M1 and M4 Mga profiles were similar, the M6 JRS4 was
      clearly distinct, even from other M6 strains. Real-time RT-PCR and Northern blots
      confirmed that established core Mga regulon genes directly activated by Mga (emm,
      scpA, sof, fba) exhibited the highest activation levels across all strains
      tested. Spy2036 encoding a cytosolic hypothetical protein was highly activated in
      all three serotypes and was called gene regulated by Mga (grm). Mga bound
      directly to Pgrm, which overlaps the Mga-regulated Psof in OF+ strains,
      suggesting that grm is part of the core Mga regulon and Mga is able to activate
      divergently transcribed genes from a single site. Furthermore, Mga activated speB
      when detectable in the wild-type strain, although direct binding of Mga to PspeB
      could not be demonstrated. Thus, Mga is able to both directly and indirectly
      regulate genes shown to be important for virulence and the metabolic homeostasis
      of GAS.

PMID- 16965518
TI  - Identification and characterization of receptors for vacuolating activity of
      subtilase cytotoxin.
AB  - Some shiga toxin-producing Escherichia coli secrete a novel AB5 cytotoxin, named
      subtilase cytotoxin (SubAB), which induces vacuole formation in addition to
      cytotoxicity in susceptible cells. By immunoprecipitation with SubAB from Vero
      cells, we discovered proteins of 100 kDa, 135 kDa and 155 kDa as potential
      candidates for its receptor. These proteins were N-glycosylated in their
      extracellular domains, a modification that was necessary for interaction with
      SubAB. Biotinylated receptors were partially purified by Datura stramonium
      agglutinin affinity chromatography and avidin-agarose and analysed by TOF mass
      spectroscopy. The peptide sequences of p135 were identical to beta1 integrin, and
      its identification was confirmed with anti-integrin beta1 antibody. The p155
      protein was identified as alpha2 integrin using anti-integrin alpha2 antibody. In
      addition, treatment of Vero cells with beta1 integrin RNAi before exposure to
      SubAB prevented vacuolating activity. These results suggested that SubAB
      recognizes alpha2beta1 integrin as a functional receptor; this first interaction
      may be an important key step leading to the SubAB-induced morphological changes
      in Vero cells.

PMID- 16965519
TI  - The solution structure of the invasive tip complex from Afa/Dr fibrils.
AB  - Afa/Dr family of adhesins are produced by pathogenic Escherichia coli strains
      that are especially prevalent in chronic diarrhoeal and recurrent urinary tract
      infections. Most notably, they are found in up to 50% of cystitis cases in
      children and 30% of pyelonephritis in pregnant women. Afa/Dr adhesins are capped
      surface fibrils that mediate recognition of the host and subsequent bacterial
      internalization. Using the newly solved three-dimensional structure of the
      minimal invasive complex (AfaDE) combined with biochemical and cellular assays,
      we reveal the architecture of the fibrillar cap and identify a novel mode of
      synergistic integrin recognition.

PMID- 16965521
TI  - CARD15 gene variants in aggressive periodontitis.
AB  - OBJECTIVE: The CARD15 gene encodes a protein that acts as an intracellular
      receptor of bacterial products, thus playing an important role in the innate
      immune response. Recently, CARD15 gene variants have been identified as a cause
      of increased susceptibility to Crohn's disease. The present study aimed to
      examine a potential association of CARD15 gene variants with aggressive
      periodontitis susceptibility. MATERIAL AND METHODS: The three main known CARD15
      gene variants (p.R702W, p.G908R, and p.L1007fsX1008) were analysed by direct
      sequencing of exon 4, 8, and 11 of the gene in a total of 86 generalized
      aggressive periodontitis patients in comparison with 67 healthy controls.
      RESULTS: The mutant allele frequencies of the CARD15 variants were low in the
      generalized aggressive periodontitis group as well as in the control group and
      not significantly different (R702W: 3.5% versus 5.2%; G908R: 1.7% versus 1.5%;
      L1007fsX1008: 5.2% versus 4.5%). Two rare variants (A755V and R791Q), previously
      described only in patients with other inflammatory diseases, were observed in
      three patients having aggressive periodontitis but not in controls. CONCLUSIONS:
      Unlike in Crohn's disease, our results did not show an association between the
      three main CARD15 mutations and aggressive periodontitis. The role of rare
      variants remains unclear.

PMID- 16965522
TI  - Scaling and root planing and chlorhexidine mouthrinses in the treatment of
      chronic periodontitis: a randomized, placebo-controlled clinical trial.
AB  - OBJECTIVE: Evaluation of the clinical and microbiological effects of scaling and
      root planing (SRP) alone or in combination with 0.12% chlorhexidine (CHX)
      rinsing. METHODS: A blind, placebo-controlled, parallel-design, randomized
      clinical trial was conducted in 29 subjects with chronic periodontitis. Subjects
      were assigned to two therapeutic groups: control (SRP+placebo) and test (SRP+CHX
      during and up to 42 days post-therapy). Clinical and microbiological [N-benzoyl
      dl-arginine-2-naphthylamide (BANA test)] examinations were performed at baseline,
      42 and 63 days post-therapy. RESULTS: Initially, intermediate sites (4-6 mm) in
      the test group showed less plaque accumulation, gingival bleeding, bleeding on
      probing and a greater reduction in attachment level and probing depth (PD) at 63
      days after treatment. The initially deep sites (>6 mm) in the CHX group also
      showed a better reduction in plaque accumulation and in PD compared with the
      control group. Both therapies led to a microbiological improvement; however, the
      test subjects showed a higher frequency of BANA-negative sites after treatment,
      which was sustained over time (p<0.001). At 63 days, the control group presented
      25 BANA-negative sites and 65 positive sites, and the test group 58 and 26,
      respectively. CONCLUSION: The combination of CHX rinses and SRP leads to clinical
      benefits and to a better reduction in BANA-positive species.

PMID- 16965523
TI  - Effect of triclosan/copolymer-containing toothpaste on the association between
      plaque and gingival bleeding: a randomized controlled clinical trial.
AB  - AIM: To study longitudinal associations between plaque and gingival bleeding and
      multilevel variance/covariance structures after introducing triclosan-containing
      toothpaste. MATERIAL AND METHODS: A 10-week, randomized, two-arm, double-masked,
      controlled clinical trial was conducted in 34 healthy, non-smoking females with
      plaque-induced gingivitis. Clinical periodontal examinations were repeated every
      other week. At week 4, test toothpaste containing 0.24% sodium
      monofluorophosphate, 0.3% triclosan, and 2% polyvinyl-methyl ether maleic acid;
      or control toothpaste containing 0.76% sodium monofluorophosphate and 0.1% sodium
      fluoride, were randomly distributed. RESULTS: Multivariate multilevel models
      indicated that, after introducing experimental toothpastes, subject random error
      was reduced from 0.6 to below 0.2. The odds ratio (OR) of bleeding on probing
      (BOP) was about 30% less in the test than in the control group (p<0.01). At the
      end of the experiment, ORs for BOP and plaque index scores 1-3 (reference 0) were
      2.1-2.4 in the control group, but 1.1-1.9 in the test group (p<0.05). No effects
      on plaque levels and calculus were observed. CONCLUSIONS: Multivariate multilevel
      modelling allows the study of fixed and random effects of experimental
      toothpastes on gingival inflammation in small sample. Triclosan appears to
      attenuate the causal association between supragingival plaque and gingival
      bleeding in gingivitis.

PMID- 16965524
TI  - Relationship between IL-1A polymorphisms and gingival overgrowth in renal
      transplant recipients receiving Cyclosporin A.
AB  - AIM: Levels of interleukin-1alpha (IL-1alpha) are elevated in periodontal
      inflammation. IL-1A gene polymorphisms are associated with inflammatory diseases.
      This study aimed to investigate IL-1A gene polymorphism in Cyclosporin A (CsA)
      treated renal transplant patients and investigate the association between this
      polymorphism and gingival crevicular fluid (GCF) levels of several cytokines.
      MATERIALS AND METHODS: Fifty-one renal transplant patients on CsA treatment (25
      with and 26 without gingival overgrowth) and 29 healthy controls were recruited
      for the study. Demographic, pharmacological and periodontal parameters were
      recorded and gingival overgrowth was assessed. RESULTS: Multiple regression
      analysis showed that genotype was significantly associated with gingival
      overgrowth (p=0.02). Carriage of the IL-1A (-889) T allele was strongly
      protective [95% confidence interval (CI): 0.046-0.77], although not significantly
      associated with IL-1alpha protein levels in GCF. IL-1alpha, IL-1beta and IL-8,
      but not IL-6, were detected in GCF of CsA-treated patients, but none of them was
      significantly associated with gingival overgrowth. CONCLUSIONS: This study is the
      first to associate a gene polymorphism as a risk factor for CsA-induced gingival
      overgrowth in renal transplant patients, demonstrating that IL-1A polymorphism
      might alter individual susceptibility to CsA. However, there was no association
      between GCF cytokine levels and the presence of gingival overgrowth or patient IL
      1A genotype.

PMID- 16965525
TI  - The critical-size supraalveolar peri-implant defect model: characteristics and
      use.
AB  - OBJECTIVE: Novel implant technologies and reconstructive therapies for alveolar
      augmentation require pre-clinical evaluation to estimate their biologic
      potential, efficacy, and safety before clinical application. The objective of
      this report is to present characteristics and use of the critical-size,
      supraalveolar, peri-implant defect model. METHODS: Bilateral extraction of the
      mandibular premolars was performed in 12 Hound Labrador mongrel dogs following
      horizontal surgical cut-down of the alveolar ridge approximating 6 mm. Each jaw
      quadrant received three custom-produced TiUnite, phi 4.0 x 10 mm threaded
      implants placed into osteotomies prepared into the extraction sites of the third
      and fourth premolars. The implants exhibited a reference notch 5 mm from the
      implant platform to facilitate surgical placement leaving 5 mm of the implant in
      a supraalveolar position, and to serve as a reference point in the radiographic,
      histologic and histometric analysis. The implants were submerged under the
      mucoperiosteal flaps for primary intention healing. Fluorescent bone markers were
      administered at weeks 3 and 4 post-surgery, and pre-euthanasia. The animals were
      euthanized following an 8-week healing interval when block biopsies were
      collected for analysis. RESULTS: Healing was generally uneventful. The
      radiographic and histometric evaluations demonstrate the limited osteogenic
      potential of this defect model. Whereas lingual peri-implant sites exhibited a
      mean (+/-SE) bone gain of 0.4+/-0.1 mm, resorption of the buccal crestal plate
      resulted in a mean bone loss of 0.4+/-0.2 mm for an overall osteogenic potential
      following sham-surgery averaging 0.0+/-0.1 mm. Overall bone density and bone
      implant contact in the contiguous resident bone averaged 79.1+/-1.1% and 76.9+/
      2.3%, respectively. CONCLUSION: The results suggest that the critical-size,
      supraalveolar, peri-implant defect model appears a rigorous tool in the
      evaluation of candidate technologies for alveolar reconstruction and
      osseointegration of endosseous oral implants. Limited innate osteogenic potential
      allows critical evaluation of osteogenic, osteoconductive, or osteoinductive
      technologies in a challenging clinical setting.

PMID- 16965527
TI  - Dental diseases--are these examples of ecological catastrophes?

PMID- 16965528
TI  - The significance of supragingival plaque accumulation in periodontal disease.

PMID- 16965529
TI  - Oxidative stress, nutrition and neutrogenomics in periodontal health and disease.

PMID- 16965530
TI  - Dental plaque as a possible risk factor for general disease--results from
      longitudinal studies.

PMID- 16965531
TI  - Oral inflammation and systemic health: is the association only an artefact?

PMID- 16965532
TI  - Systemic effects of periodontitis.

PMID- 16965533
TI  - Periodontal therapy and preterm birth.

PMID- 16965534
TI  - Periodontics: current concepts and emerging trends.

PMID- 16965535
TI  - FOXM1c transactivates the human c-myc promoter directly via the two TATA boxes P1
      and P2.
AB  - FOXM1c transactivates the c-myc promoter via the P1 and P2 TATA boxes using a new
      mechanism. Whereas the P1 TATA box TATAATGC requires its sequence context to be
      FOXM1c responsive, the P2 TATA box TATAAAAG alone is sufficient to confer FOXM1c
      responsiveness to any minimal promoter. FOXM1c transactivates by binding to the
      TATA box as well as directly to TATA-binding protein, transcription factor IIB
      and transcription factor IIA. This new transactivation mechanism is clearly
      distinguished from the function of FOXM1c as a conventional transcription factor.
      The central domain of FOXM1c functions as an essential domain for activation via
      the TATA box, but as an inhibitory domain (retinoblastoma protein-independent
      transrepression domain and retinoblastoma protein-recruiting negative regulatory
      domain) for transactivation via conventional FOXM1c-binding sites. Each promoter
      with the P2 TATA box TATAAAAG is postulated to be transactivated by FOXM1c. This
      was demonstrated for the promoters of c-fos, hsp70 and histone H2B/a. A database
      search revealed almost 300 probable FOXM1c target genes, many of which function
      in proliferation and tumorigenesis. Accordingly, dominant-negative FOXM1c
      proteins reduced cell growth approximately threefold, demonstrating a
      proliferation-stimulating function for wild-type FOXM1c.

PMID- 16965536
TI  - Analysis of protein interactions within the cytokinin-signaling pathway of
      Arabidopsis thaliana.
AB  - The signal of the plant hormone cytokinin is perceived by membrane-located sensor
      histidine kinases and transduced by other members of the plant two-component
      system. In Arabidopsis thaliana, 28 two-component system proteins
      (phosphotransmitters and response regulators) act downstream of three receptors,
      transmitting the signal from the membrane to the nucleus and modulating the
      cellular response. Although the principal signaling mechanism has been
      elucidated, redundancy in the system has made it difficult to understand which of
      the many components interact to control the downstream biological processes.
      Here, we present a large-scale interaction study comprising most members of the
      Arabidopsis cytokinin signaling pathway. Using the yeast two-hybrid system, we
      detected 42 new interactions, of which more than 90% were confirmed by in vitro
      coaffinity purification. There are distinct patterns of interaction between
      protein families, but only a few interactions between proteins of the same
      family. An interaction map of this signaling pathway shows the Arabidopsis
      histidine phosphotransfer proteins as hubs, which interact with members from all
      other protein families, mostly in a redundant fashion. Domain-mapping experiments
      revealed the interaction domains of the proteins of this pathway. Analyses of
      Arabidopsis histidine phosphotransfer protein 5 mutant proteins showed that the
      presence of the canonical phospho-accepting histidine residue is not required for
      the interactions. Interaction of A-type response regulators with Arabidopsis
      histidine phosphotransfer proteins but not with B-type response regulators
      suggests that their known activity in feedback regulation may be realized by
      interfering at the level of Arabidopsis histidine phosphotransfer protein
      mediated signaling. This study contributes to our understanding of the protein
      interactions of the cytokinin-signaling system and provides a framework for
      further functional studies in planta.

PMID- 16965537
TI  - The physiologic role of alternative oxidase in Ustilago maydis.
AB  - Alternative oxidase (AOX) is a ubiquitous respiratory enzyme found in plants,
      fungi, protists and some bacterial species. One of the major questions about this
      enzyme is related to its metabolic role(s) in cellular physiology, due to its
      capacity to bypass the proton-pumping cytochrome pathway, and as a consequence it
      has great energy-wasting potential. In this study, the physiological role and
      regulatory mechanisms of AOX in the fungal phytopathogen Ustilago maydis were
      studied. We found evidence for at least two metabolic functions for AOX in this
      organism, as a major part of the oxidative stress-handling machinery, a well
      described issue, and as part of the mechanisms that increase the metabolic
      plasticity of the cell, a role that might be valuable for organisms exposed to
      variations in temperature, nutrient source and availability, and biotic or
      abiotic factors that limit the activity of the cytochrome pathway. Experiments
      under different culture conditions of ecological significance for this organism
      revealed that AOX activity is modified by the growth stage of the culture, amino
      acid availability and growth temperature. In addition, nucleotide content,
      stimulation of AOX by AMP and respiratory rates obtained after inhibition of the
      cytochrome pathway showed that fungal/protist AOX is activated under low-energy
      conditions, in contrast to plant AOX, which is activated under high-energy
      conditions. An estimation of the contribution of AOX to cell respiration was
      performed by comparing the steady-state concentration of adenine nucleotides, the
      mitochondrial membrane potential, and the respiratory rate.

PMID- 16965538
TI  - Site-specific casein kinase 1epsilon-dependent phosphorylation of Dishevelled
      modulates beta-catenin signaling.
AB  - Careful regulation of the Wnt-Beta-catenin signaling pathway is critical to many
      aspects of development and cancer. Casein kinase Iepsilon is a Wnt-activated
      positive regulator of this pathway. Members of the Dishevelled family have been
      identified as key substrates of casein kinase I (CKI). However, the specific
      sites phosphorylated in vivo by CKI and their relative importance in the
      physiologic regulation of these proteins in the canonical Wnt-beta-catenin
      signaling pathway remain unclear. To address this question, recombinant mouse
      Dishevelled (mDvl-1) was phosphorylated by CKIin vitro and phosphorylation sites
      were identified by MS. CKI phosphorylation of mDvl-1 at two highly conserved
      residues, serines 139 and 142, was observed by MS and confirmed by phosphopeptide
      mapping of in vivo phosphorylated protein. Phosphorylation of these sites is
      dependent on casein kinase I epsilon activity in vivo. Phenotypic analysis of
      mutant mDvl-1 indicates that phosphorylation of these sites stimulates the Dvl
      activated beta-catenin-dependent Wnt signaling pathway in both cell culture and
      in Xenopus development. Casein kinase I epsilon is a Wnt-regulated kinase, and
      regulated phosphorylation of Dvl allows fine tuning of the Wnt-beta-catenin
      signaling pathway.

PMID- 16965539
TI  - A unique vertebrate histone H1-related protamine-like protein results in an
      unusual sperm chromatin organization.
AB  - Protamine-like proteins constitute a group of sperm nuclear basic proteins that
      have been shown to be related to somatic linker histones (histone H1 family).
      Like protamines, they usually replace the chromatin somatic histone complement
      during spermiogenesis; hence their name. Several of these proteins have been
      characterized to date in invertebrate organisms, but information about their
      occurrence and characterization in vertebrates is still lacking. In this sense,
      the genus Mullus is unique, as it is the only known vertebrate that has its sperm
      chromatin organized by virtually only protamine-like proteins. We show that the
      sperm chromatin of this organism is organized by two type I protamine-like
      proteins (PL-I), and we characterize the major protamine-like component of the
      fish Mullus surmuletus (striped red mullet). The native chromatin structure
      resulting from the association of these proteins with DNA was studied by
      micrococcal nuclease digestion as well as electron microscopy and X-ray
      diffraction. It is shown that the PL-I proteins organize chromatin in parallel
      DNA bundles of different thickness in a quite distinct arrangement that is
      reminiscent of the chromatin organization of those organisms that contain
      protamines (but not histones) in their sperm.

PMID- 16965540
TI  - Critical role of His369 in the reactivity of Pseudomonas aeruginosa cytochrome
      cd1 nitrite reductase with oxygen.
AB  - In the denitrification pathway, Pseudomonas aeruginosa cytochrome cd1 nitrite
      reductase catalyzes the reduction of nitrite to nitric oxide; in vitro, this
      enzyme is also competent in the reduction of O2 to 2H2O. In this article, we
      present a comparative kinetic study of the O2 reaction in the wild-type nitrite
      reductase and in three site-directed mutants (Tyr10-->Phe, His369-->Ala and
      His327-->Ala/His369-->Ala) of the amino acid residues close to the d1 heme on the
      distal side. The results clearly indicate that His369 is the key residue in the
      control of reactivity, as its substitution with Ala, previously shown to affect
      the reduction of nitrite, also impairs the reaction with O2, affecting both the
      properties and lifespan of the intermediate species. Our findings allow the
      presentation of an overall picture for the reactivity of cytochrome cd1 nitrite
      reductase and extend our previous conclusion that the conserved distal histidines
      are essential for the binding to reduced d1 heme of different anions, whether a
      substrate such as nitrite, a ligand such as cyanide, or an intermediate in the O2
      reduction. Moreover, we propose that His369 also exerts a protective role against
      degradation of the d1 heme, by preventing the formation and adverse effects of
      the reactive O2 species (never present in significant amounts in wild-type
      cytochrome cd1 nitrite reductase), a finding with clear physiological
      implications.

PMID- 16965541
TI  - Molecular events during leukocyte diapedesis.
AB  - The recruitment of leukocytes from the circulation into tissues requires
      leukocyte migration through the vascular endothelium. The mechanisms by which
      leukocytes attach and firmly adhere to the endothelial cell surface have been
      studied in detail. However, much less is known about the last step in this
      process, the diapedesis of leukocytes through the vascular endothelium. This
      minireview focuses on the interactions between leukocyte and endothelial cell
      adhesion molecules that are important during leukocyte extravasation. In the past
      few years a series of endothelial cell surface and adhesion molecules have been
      identified that are located at endothelial cell contacts and found to participate
      in leukocyte diapedesis. These junctional cell adhesion molecules are believed to
      have an active role in controlling the opening and closure of endothelial cell
      contacts to allow the passage of leukocytes between adjacent endothelial cells.
      Alternatively, leukocytes can cross the endothelium at nonjunctional locations,
      with leukocytes migrating through a single endothelial cell. Further work is
      clearly needed to understand, in greater detail, the molecular mechanisms that
      allow leukocytes to cross the endothelium via either the paracellular or the
      transcellular pathway.

PMID- 16965542
TI  - PAR-1-dependent pp60src activation is dependent on protein kinase C and increased
      [Ca2+]: evidence that pp60src does not regulate PAR-1-dependent Ca2+ entry in
      human platelets.
AB  - BACKGROUND: The role of the tyrosine kinase pp60src in PAR-1-dependent Ca2+ entry
      was investigated in human platelets. pp60src plays a role in thapsigargin (TG)
      evoked store-operated Ca2+ entry (SOCE), which is thought to be a major component
      of thrombin-evoked Ca2+ entry. METHODS: pp60src tyr416 phosphorylation was used
      to assess pp60src activation. Fura-2-loaded platelets were used to monitor
      intracellular Ca2+ concentration ([Ca2+]i). RESULTS: Activation of PAR-1 with the
      specific agonist SFLLRN increased pp60src activation within 10 s. This required
      phospholipase C (PLC) activity, Ca2+ release and a rise in intracellular Ca2+.
      PP2, an inhibitor of Src-family tyrosine kinases, inhibited SFLLRN-evoked Ca2+
      entry, but also inhibited Ca2+ release and the extrusion of Ca2+ by the plasma
      membrane Ca2+ ATPase. Actin polymerization and conventional protein kinase C
      (cPKC) activity were required for TG- and SFLLRN-evoked pp60src activation.
      Although Go6976, an inhibitor of cPKCs, inhibited TG-evoked SOCE, it had little
      effect on SFLLRN- or thrombin-evoked Ca2+ entry. CONCLUSIONS: These data indicate
      that stimulation of PAR-1 leads to activation of pp60src in human platelets,
      through PLC and cPKC activation, Ca2+ release and actin polymerization. However,
      as PKC and actin polymerization are not needed for SFLLRN-evoked Ca2+ entry, we
      suggest that pp60src is also not required. The apparent inhibition of SFLLRN
      evoked Ca2+ entry by PP2 is likely to be secondary to reduced Ca2+ release. These
      data argue against a contribution of this SOCE pathway to PAR-1-dependent Ca2+
      entry.

PMID- 16965543
TI  - P2Y receptor-mediated excitation in the posterior hypothalamus.
AB  - Histaminergic neurons located in the posterior hypothalamus (tuberomamillary
      nucleus, TMN) project widely through the whole brain controlling arousal and
      attention. They are tonically active during wakefulness but cease firing during
      sleep. As a homeostatic theory of sleep involves ATP depletion and adenosine
      accumulation in the brain, we investigated the role of ATP and its analogues as
      well as adenosine on neuronal activity in the TMN. We show increased firing of
      rat TMN neurons by ATP, ADP, UTP and 2meSATP, indicating activation of receptors
      belonging to the P2Y family. Adenosine affected neither membrane potential nor
      firing of these cells. Single-cell reverse transcriptase-polymerase chain
      reaction revealed that P2Y1 and P2Y4 are prevailing receptors in TMN neurons.
      P2Y1 receptor mRNA was detected with a higher frequency in 2-week-old than in 4
      week-old rats; in accordance, 2meSATP was more potent than ATP. Semi-quantitative
      real-time polymerase chain reaction revealed a developmental downregulation of
      mRNA levels for P2Y1 and P2Y4 receptors. Immunocytochemistry demonstrated
      neuronal and glial localization of the P2Y1 receptor protein. Network activity
      measured with multielectrode arrays in primary cultures made from the posterior
      hypothalamus was enhanced by UTP and 2meSATP (P2Y4 and P2Y1 agonists,
      respectively). ATP caused an inhibition of firing, which was reversed in the
      presence of suramin or gabazine [gamma-aminobutyric acid (GABA)A receptor
      antagonist], indicating that GABAergic neurons are preferentially activated by
      ATP in this network. Excitation of the wake-active TMN neurons by nucleotides and
      the lack of adenosine action may be important factors in sleep-wake regulation.

PMID- 16965544
TI  - Changes of spine density and dendritic complexity in the prefrontal cortex in
      offspring of mothers exposed to stress during pregnancy.
AB  - Both chronic stress in adulthood and episodes of stress in the early postnatal
      period have been shown to interfere with neuronal development in limbic
      prefrontal cortical regions. The present study in rats showed for the first time
      that the development of layer II/III pyramidal neurons in the dorsal anterior
      cingulate (ACd) and orbitofrontal cortex (OFC) is significantly affected in
      offspring of mothers exposed to stress during pregnancy. In prenatally stressed
      (PS) male rat pups the ACd and OFC showed significantly lower spine densities on
      the apical dendrite (ACd, -20%; OFC, -25%), on basal dendrites reduced spine
      densities where found only in the OFC (-20% in PS males). Moreover, in both
      cortical areas a significant reduction of dendritic length was observed in PS
      males compared to control offspring, which was confined to the apical dendrites
      (ACd, -30%, OFC, -26%). Sholl analysis revealed that these alterations were
      accompanied by a significantly reduced complexity of the dendritic trees in both
      cortical regions. PS females displayed reductions of dendritic spine densities in
      the ACd and OFC on both the basal (ACd, -21%; OFC, -20%) and apical dendrites
      (ACd, -21%; OFC, -21%), however, in contrast to the findings in PS males, no
      dendritic atrophy was detected in the PS females. These findings demonstrate that
      gestational stress leads to significant alterations of prefrontal neuronal
      structure in the offspring of the stressed mothers in a sex-specific manner.

PMID- 16965545
TI  - Rapid pH and PO2 changes in the tissue recording chamber during stoppage of a gas
      equilibrated perfusate: effects on calcium currents in ventral horn neurons.
AB  - In vitro studies often use bicarbonate-buffered saline solutions to mimic the
      normal extracellular environment of tissues. These solutions are typically
      equilibrated with gaseous O2 and CO2, the latter interacting with bicarbonate
      ions to maintain a physiological pH. In vitro tissue chambers, like those used
      for electrophysiology, are usually continually perfused with the gassed buffer,
      but stopping the perfusion to add expensive chemicals or acquire imaging data is
      a common practice. The present study demonstrates that this procedure leads to
      rapid (< 30 s) increases in pH and decreases in PO2 of the detained solution in
      the tissue chamber. During the first 200 s, pH increased by 0.4 units and
      resulted in a 25% PO2 reduction of the detained solution. The rates of these
      changes were dependent on the volume of solution in the chamber. In experiments
      using acute transverse slices from the lumbar spinal cord of neonatal (postnatal
      day 0-10) mice, perfusion stoppage of the same duration was accompanied by a
      34.7% enhancement of the peak voltage-gated calcium current recorded from ventral
      horn neurons. In these cells both low voltage-activated and high voltage
      activated currents were affected. These currents were unaffected by decreasing
      PO2 when a CO2-independent buffer was used, suggesting that changes in pH were
      responsible for the observed effects. It is concluded that the procedure of
      stopping a bicarbonate/CO2-buffered perfusate results in rapid changes in pH and
      PO2 of the solution detained in the tissue chamber, and that these changes have
      the potential to covertly influence experimental results.

PMID- 16965546
TI  - Is the CCK2 receptor essential for normal regulation of body weight and
      adiposity?
AB  - Cholecystokinin (CCK) is a gastrointestinal satiety signal released from the
      duodenum to terminate feeding, via CCK1 receptors. CCK2 receptors are considered
      to be involved in anxiety. CCK2 receptor knockout mice have increased body weight
      and food intake. Little is known regarding the effects of CCK2 receptor
      deficiency on adipose distribution and hypothalamic feeding regulators such as
      neuropeptide Y (NPY), a powerful stimulator of feeding. Adult (10 week) CCK2
      receptor knockout and wild-type mice were anaesthetized and killed by
      decapitation. Brain sections, organs and fat tissue were dissected. Plasma
      leptin, insulin and brain NPY content were measured by radioimmunoassay. Female
      CCK2 receptor knockout mice weighed more than control mice (22.0 +/- 0.2 vs. 19.9
      +/- 0.4 g, P < 0.05), with this difference being less marked in male mice (26.4
      +/- 0.4 vs. 25.6 +/- 0.6 g). Fat masses in all locations sampled were
      significantly smaller in CCK2 receptor knockout mice of both genders (P < 0.05),
      resulting in lower plasma leptin and insulin levels. NPY concentrations were
      significantly increased in arcuate nucleus and anterior hypothalamus in both male
      and female CCK2 receptor knockout mice, and total hypothalamic NPY content was
      increased by 7 and 9% in males and females, respectively (P < 0.05). CCK2
      receptor deletion was associated with increased body weight and hypothalamic NPY
      content, but reduced fat masses and plasma leptin and insulin. Increased NPY
      might contribute to increased food intake in CCK2 receptor knockout mice. Further
      work needs to focus on the metabolic changes.

PMID- 16965547
TI  - Irreversible blockade of monoamine oxidases reveals the critical role of 5-HT
      transmission in locomotor response induced by nicotine in mice.
AB  - Although nicotine is generally considered as the main compound responsible for
      addictive properties of tobacco, some experimental data indicate that nicotine
      does not exhibit all the characteristics of other substances of misuse such as
      psychostimulants and opiates. For example, nicotine generally fails to induce
      locomotor response in mice and self-administration of nicotine is difficult to
      obtain in rats. We have shown recently that a pretreatment with mixed
      irreversible monoamine oxidase inhibitors (MAOIs), such as tranylcypromine,
      triggers a locomotor response to nicotine in mice and induces a robust self
      administration of nicotine in rats. We show here that when mice were pretreated
      with enhancers of extracellular levels of noradrenaline, dopamine or serotonin (D
      amphetamine, GBR12783 or para-chloro-amphetamine, respectively) and injected with
      nicotine (1 mg/kg), only those animals pretreated with para-chloro-amphetamine
      exhibited a specific locomotor response to nicotine. These data indicate a
      critical role of serotonin in nicotine-induced locomotor activity in mice. This
      was further confirmed in microdialysis experiments showing that nicotine induces
      an increase in extracellular serotonin levels in the ventral striatum in mice
      pretreated with tranylcypromine. This effect of nicotine on extracellular
      serotonin levels was absent in mice lacking the beta2-subunit of the nicotinic
      acetylcholine receptor. Our data suggest that mixed irreversible MAOIs contained
      in tobacco facilitate the effects of nicotine on serotonin release, thus allowing
      the locomotor and rewarding effects of nicotine.

PMID- 16965548
TI  - Different signal transduction cascades are activated simultaneously in the rat
      insular cortex and hippocampus following novel taste learning.
AB  - Novel taste learning is a robust one-trial incidental learning process, dependent
      on functional activity of the insular (taste) cortex. In contrast to that of the
      cortex, the role of the hippocampus in taste learning is controversial. We set
      out to identify the time courses of the activation of mitogen-associated protein
      kinase (MAPK), transcription factor cAMP-response element-binding protein (CREB)
      and Akt/PKB (protein kinase B) in the insular cortex and hippocampus of rats
      subsequent to novel taste learning. Following taste learning, an early response
      (20 min) occurred at the same time in the insular cortex and the hippocampus.
      However, whereas MAPK was activated specifically in the insular cortex, CREB and
      Akt were phosphorylated in the hippocampus but not in the cortex. In addition,
      the immediate early gene, CCAAT/enhancer binding protein (C/EBPbeta) was induced
      in both the hippocampus and the insular cortex 18 h following taste learning. The
      results demonstrate, for the first time, correlative activation and gene
      expression in the hippocampus following novel taste learning. Moreover, the
      results suggest that different signal transduction cascades necessary for taste
      learning are activated in concert in different brain structures, to enable taste
      learning and consolidation.

PMID- 16965549
TI  - A polymorphism in lipoprotein lipase affects the severity of Alzheimer's disease
      pathophysiology.
AB  - Emerging evidences indicate a role for lipoprotein lipase (LPL) in degenerative
      states. Genetic variations in the LPL gene were previously associated to lipid
      imbalance and coronary artery disease (CAD) risk and severity, a condition that
      shares pathological features with common Alzheimer's disease (AD). To evaluate
      whether these genetic variations associate with the risk and pathophysiology of
      common AD, autopsy-confirmed patients (242 controls, 153 AD) were genotyped for a
      PvuII single nucleotide polymorphism (SNP; rs285; referred to as the P+ allele)
      of LPL. Brain LPL mRNA levels, cholesterol levels, amyloid concentration, senile
      plaques and neurofibrillary tangles density counts were measured and contrasted
      with specific LPL genotypes. When adjusted for age and sex, homozygosity for the
      P+ allele resulted in an odds ratio of 2.3 for the risk of developing AD. More
      importantly, we report that the presence of the P+ allele of LPL significantly
      affects its mRNA expression level (n = 51; P = 0.026), brain tissue cholesterol
      levels (n = 55; P = 0.0013), neurofibrillary tangles (n = 52; P = 0.025) and
      senile plaque (n = 52; P = 0.022) densities. These results indicate that a common
      polymorphism in the lipoprotein lipase gene modulates the risk level for sporadic
      AD in the eastern Canadian population but more importantly, indirectly modulates
      the pathophysiology of the brain in autopsy-confirmed cases.

PMID- 16965550
TI  - Reticulons RTN3 and RTN4-B/C interact with BACE1 and inhibit its ability to
      produce amyloid beta-protein.
AB  - Beta-secretase beta-site APP cleaving enzyme 1 (BACE1), is a membrane-bound
      aspartyl protease necessary for the generation of amyloid beta-protein (Abeta),
      which accumulates in the brains of individuals with Alzheimer's disease (AD). To
      gain insight into the mechanisms by which BACE1 activity is regulated, we used
      proteomic methods to search for BACE1-interacting proteins in human neuroblastoma
      SH-SY5Y cells, which overexpress BACE1. We identified reticulon 4-B (RTN4-B; Nogo
      B) as a BACE1-associated membrane protein. Co-immunoprecipitation experiments
      confirmed a physical association between BACE1 and RTN4-B, RTN4-C (the shortest
      isoform of RTN-4), and their homologue reticulon 3 (RTN3), both in SH-SY5Y cells
      and in transfected human embryonic kidney (HEK) 293 cells. Overexpression of
      these reticulons (RTNs) resulted in a 30-50% reduction in the secretion of both
      Abeta40 and Abeta42 from HEK293 cells expressing the AD-associated Swedish mutant
      amyloid precursor protein (APP), but did not affect Abeta secretion from cells
      expressing the APP beta-C-terminal fragment (beta-CTF), indicating that these
      RTNs can inhibit BACE1 activity. Furthermore, a BACE1 mutant lacking most of the
      N-terminal ectodomain also interacted with these RTNs, suggesting that the
      transmembrane region of BACE1 is critical for the interaction. We also observed a
      similar interaction between these RTNs and the BACE1 homologue BACE2. Because
      RTN3 and RTN4-B/C are substantially expressed in neural tissues, our findings
      suggest that they play important roles in the regulation of BACE1 function and
      Abeta production in the brain.

PMID- 16965551
TI  - Heterogeneity in low voltage-activated Ca2+ channel-evoked Ca2+ responses within
      neurons of the thalamic paraventricular nucleus.
AB  - Low voltage-activated Ca2+ channels (LVA or T-type Ca2+ channels) are crucial to
      burst firing and oscillations in thalamocortical relay cells and are exhibited by
      neurons in the paraventricular nucleus of thalamus (PVT), a dorsal midline
      nucleus deemed important in the neural representation of motivational behaviours.
      We used a functional approach (whole-cell patch-clamp electrophysiology combined
      with confocal laser scanning microscopy) to analyse the spatial distribution of
      LVA Ca2+ channel-evoked Ca2+ transients in PVT neurons. We observed that the
      magnitude of LVA Ca2+ channel-evoked Ca2+ transients was significantly greater in
      proximal dendrites (located up to 20 microm from the soma) than in the soma. In
      addition, the magnitudes of these Ca2+ transients varied significantly not only
      among different dendrites of the same cell but also within individual dendrites.
      These findings suggest that LVA Ca2+ channels are expressed (i) predominantly on
      the proximal dendrites and (ii) heterogeneously within individual dendrites of
      PVT neurons. The spatial characteristics of dendritic LVA Ca2+ channels in PVT
      neurons suggest that these channels may regulate burst firing by modulating
      dendritic afferent inputs.

PMID- 16965552
TI  - Electrical coupling underlies theta rhythm in freely moving cats.
AB  - The role of gap junction coupling in the generation of theta rhythms in freely
      moving cats was investigated in a present study. Two gap junction blockers,
      carbenoxolone and quinine, were administered intraperitoneally and
      intrahippocampally; both gap junction blockers abolished or diminished
      (respectively) hippocampal formation theta. The inhibitory effect developed
      approximately 30 min after drug administration. This effect was found to be
      reversible. Our results provide the first direct in vivo evidence for the
      contribution of gap junction communication in mechanisms of neural synchrony,
      underlying the production of theta in in vivo conditions.

PMID- 16965553
TI  - Modulating the proteinase inhibitory profile of a plant cystatin by single
      mutations at positively selected amino acid sites.
AB  - Cysteine proteinase inhibitors of the cystatin superfamily have several important
      functions in plants, including the inhibition of exogenous cysteine proteinases
      during herbivory or infection. Here we used a maximum-likelihood approach to
      assess whether plant cystatins, like other proteins implicated in host-pest
      interactions, have been subject to positive selection during the course of their
      evolution. Several amino acid sites were identified as being positively selected
      in cystatins from either Poaceae (monocots) and Solanaceae (dicots). These
      hypervariable sites were located at strategic positions on the protein: on each
      side of the conserved glycine residues in the N-terminal trunk, within the first
      and second inhibitory loops entering the active site of target enzymes, and
      surrounding the larfav motif, a sequence of unknown function conserved among
      plant cystatins. Supporting the assumption that positively selected,
      hypervariable sites are indicative of amino acid sites implicated in functional
      diversity, mutants of the 8th cystatin unit of tomato multicystatin including
      alternative residues at positively selected sites in the N-terminal trunk
      exhibited highly variable affinities for the cysteine proteases papain, cathepsin
      B and cathepsin H. Overall, these observations support the hypothesis that plant
      cystatins have been under selective pressure to evolve in response to predatory
      challenges by herbivorous enemies. They also indicate the potential of site
      directed mutagenesis at positively selected sites for the generation of cystatins
      with improved binding properties.

PMID- 16965554
TI  - The C-terminal half of Phytophthora infestans RXLR effector AVR3a is sufficient
      to trigger R3a-mediated hypersensitivity and suppress INF1-induced cell death in
      Nicotiana benthamiana.
AB  - The RXLR cytoplasmic effector AVR3a of Phytophthora infestans confers avirulence
      on potato plants carrying the R3a gene. Two alleles of Avr3a encode secreted
      proteins that differ in only three amino acid residues, two of which are in the
      mature protein. Avirulent isolates carry the Avr3a allele, which encodes AVR3aKI
      (containing amino acids C19, K80 and I103), whereas virulent isolates express
      only the virulence allele avr3a, encoding AVR3aEM (S19, E80 and M103). Only the
      AVR3aKI protein is recognized inside the plant cytoplasm where it triggers R3a
      mediated hypersensitivity. Similar to other oomycete avirulence proteins, AVR3aKI
      carries a signal peptide followed by a conserved motif centered on the consensus
      RXLR sequence that is functionally similar to a host cell-targeting signal of
      malaria parasites. The interaction between Avr3a and R3a can be reconstructed by
      their transient co-expression in Nicotiana benthamiana. We exploited the N.
      benthamiana experimental system to further characterize the Avr3a-R3a
      interaction. R3a activation by AVR3aKI is dependent on the ubiquitin ligase
      associated protein SGT1 and heat-shock protein HSP90. The AVR3aKI and AVR3aEM
      proteins are equally stable in planta, suggesting that the difference in R3a
      mediated death cannot be attributed to AVR3aEM protein instability. AVR3aKI is
      able to suppress cell death induced by the elicitin INF1 of P. infestans,
      suggesting a possible virulence function for this protein. Structure-function
      experiments indicated that the 75-amino acid C-terminal half of AVR3aKI, which
      excludes the RXLR region, is sufficient for avirulence and suppression functions,
      consistent with the view that the N-terminal region of AVR3aKI and other RXLR
      effectors is involved in secretion and targeting but is not required for effector
      activity. We also found that both polymorphic amino acids, K80 and I103, of
      mature AVR3a contribute to the effector functions.

PMID- 16965555
TI  - The protein kinase genes MAP3K epsilon 1 and MAP3K epsilon 2 are required for
      pollen viability in Arabidopsis thaliana.
AB  - We have used reverse-genetic analysis to investigate the function of MAP3K
      epsilon 1 and MAP3K epsilon 2, a pair of closely related Arabidopsis thaliana
      genes that encode protein kinases. Plants homozygous for either map3k epsilon 1
      or map3k epsilon 2 displayed no apparent mutant phenotype, whereas the double
      mutant combination caused pollen lethality. Transmission of the double-mutant
      combination through the female gametophyte was normal. Tetrad analysis performed
      using the Arabidopsis quartet mutation demonstrated that the pollen-lethal
      phenotype segregated at meiosis with the map3k epsilon 1;map3k epsilon 2
      genotype. We used transmission electron microscopy to determine that double
      mutant pollen grains develop plasma membrane irregularities following pollen
      mitosis I. Analysis of the subcellular localization of a yellow fluorescent
      protein (YFP):MAP3Kepsilon1 fusion protein using confocal microscopy and
      biochemical fractionation indicated that a substantial portion of the
      MAP3Kepsilon1 present in Arabidopsis cells is localized to the plasma membrane.
      Taken together, our results suggest that MAP3Kepsilon1 is required for the normal
      functioning of the plasma membrane in developing Arabidopsis pollen.

PMID- 16965557
TI  - Nonbacterial thrombotic endocarditis with recurrent embolic events as
      manifestation of ovarian neoplasm.
AB  - We describe the case of a 43-year-old woman with transient ischemic neurologic
      deficits and recurrent systemic and pulmonary emboli in whom infectious work-up
      and extensive thrombophilic evaluation were unremarkable. Transesophageal
      echocardiography (TEE) established the diagnosis of nonbacterial thrombotic
      endocarditis (NBTE). This is a rare condition often associated with
      hypercoagulable states or advanced malignancy such as adenocarcinomas,
      characterized by cardiac vegetations along valvular coaptation lines without
      destruction of leaflets. In our patient, we diagnosed an ovarian clear cell
      adenocarcinoma, a malignant disorder that has been rarely reported in association
      with NBTE. This case illustrates that NBTE can present as an atypical
      manifestation of malignancy and must be distinguished from infective
      endocarditis, which implies a different therapeutic strategy. When confronted
      with findings of NBTE without a clear etiology, an occult neoplasm must be
      excluded. Anticoagulant therapy is the mainstay of treatment. However, cardiac
      vegetations may require surgical intervention in rare instances.

PMID- 16965558
TI  - Recoverable cognitive dysfunction at hospital admission in older persons during
      acute illness.
AB  - BACKGROUND: While acute illness and hospitalization represent pivotal events for
      older persons, their contribution to recoverable cognitive dysfunction (RCD) has
      not been well examined. OBJECTIVE: Our goals were to estimate the frequency and
      degree of RCD in an older hospitalized cohort; to examine the relationship of RCD
      with delirium and dementia; and to determine 1-year cognitive outcomes. DESIGN:
      Prospective cohort study. PARTICIPANTS: Four hundred and sixty patients aged > or
      =70 years drawn from consecutive admissions to an academic hospital.
      MEASUREMENTS: Patients underwent interviews daily during hospitalization and at 1
      year. The primary outcome was RCD, defined as an admission Mini-Mental State
      Examination (MMSE) score that improved by 3 or more points by discharge. RESULTS:
      Recoverable cognitive dysfunction occurred in 179 of 460 (39%) patients, with
      MMSE impairment at baseline ranging from 3 to 13 points (median=5.0 points). The
      majority of cases were not characteristic of either delirium or dementia, as 144
      of 179 (80%) cases did not meet criteria for delirium, and 133 of 164 (81%) cases
      did not meet criteria for dementia at baseline. In multivariable analysis
      controlling for baseline MMSE level, 3 factors were predictive of RCD: higher
      educational level, preadmission functional impairment, and higher illness
      severity. At 1 year, further improvement in MMSE score occurred in 38 of 92 (41%)
      patients with RCD. Recoverable cognitive dysfunction was independently predictive
      of 1-year mortality with an adjusted odds ratio of 1.82 (95% confidence interval
      [95% CI] 1.03 to 3.20). CONCLUSIONS: Acute illness is accompanied by a high rate
      of RCD that is neither characteristic of delirium or dementia. Our observations
      underscore the reversible nature of this cognitive dysfunction with continued
      improvement over the ensuing year, and highlight the potential clinical
      implications of this under-recognized phenomenon.

PMID- 16965559
TI  - A prospective trial of a new policy eliminating signed consent for do not
      resuscitate orders.
AB  - BACKGROUND: Some institutions require patients and families to give signed
      consent for Do Not Resuscitate (DNR) orders, especially in New York State. As
      this may be a barrier to discussions about DNR orders,we changed a signed consent
      policy to a witnessed verbal consent policy,simplified and modified the DNR order
      forms, and educated the staff at 1 hospital, comparing the effects with an
      affiliated hospital where the policy was not changed. DESIGN: Prospective natural
      experiment with intervention and comparison sites. SUBJECTS AND MEASUREMENTS: Pre
      and postintervention, we surveyed house officers' confidence and attitudes,
      reviewed charts to assess the number of concurrent care concerns (CCCs) addressed
      per DNR order (e.g., limits on intubation or blood products or need for
      hospice),and at the intervention hospital, measured the stress levels of
      surrogates consenting for DNR orders using the Horowitz Impact of Event Scale. We
      also surveyed staff perceptions about the policy following the change. RESULTS:
      At the intervention hospital, the percentage of house officers reporting low
      confidence in their ability to obtain consent for DNR orders declined
      postintervention (24% to 7%, P=.002), while there was no significant change at
      the comparison hospital (20% vs 15%, P=.45).Among intervention hospital house
      officers, there were declines in percent reporting difficulty talking to patients
      and families about DNR orders, but no significant changes at the comparison
      hospital.At the intervention hospital, the mean number of CCCs/DNR order
      Increased (1.0 pre to 4.2 post, P<.001). but did not change significantly(1.2 pre
      to 1.4 post) at the comparison hospital. The mean total stress score for
      intervention hospital surrogates declined postintervention(23.6 to 17.3, P=.02),
      indicating lower stress. House officers(98%), attendings (59%), and nurses (79%}
      thought the new policy was better for families. CONCLUSIONS: The policy change
      was well received and associated with improved house officer attitudes, more
      attention to patients'concurrent care concerns, and decreased surrogate stress.
      The results suggest that DNR orders can be made simpler and clearer, and raise
      questions about policies requiring signed consent for DNR orders.

PMID- 16965560
TI  - Training primary care clinicians in maintenance care for moderated alcohol use.
AB  - OBJECTIVE: To evaluate whether training primary care clinicians in maintenance
      care for patients who have changed their drinking influences practice behavior.
      DESIGN: We randomized 15 physician and 3 mid-level clinicians in 2 primary care
      offices in a 2:1 design. The 12 intervention clinicians received a total of 2
      (1/4) hours of training in the maintenance care of alcohol problems in remission,
      a booster session, study materials and chart-based prompts at eligible patients'
      visits. Six controls provided usual care. Screening forms in the waiting rooms
      identified eligible patients, defined as those who endorsed: 1 or more items on
      the CAGE questionnaire or that they had an alcohol problem in the past; that they
      have "made a change in their drinking and are trying to keep it that way"; and
      that they drank <15 (men) or <10 (women) drinks per week in the past month. Exit
      interviews with patients evaluated the clinician's actions during the visit.
      RESULTS: Of the 164 patients, 62% saw intervention clinicians. Compared with
      patients of control clinicians, intervention patients were more likely to report
      that their clinician asked about their alcohol history (odds ratio, 2.8; 95%
      confidence interval, 1.3, 5.8). Intervention clinicians who asked about the
      alcohol history were more likely to assess prior and planned alcohol treatment,
      assist through offers for prescriptions and treatment referral, and receive
      higher satisfaction ratings for the visit. CONCLUSIONS: Systemic prompts and
      training in the maintenance care of alcohol use disorders in remission might
      increase primary care clinicians' inquiries about the alcohol history as well as
      appropriate assessment and intervention after an initial inquiry.

PMID- 16965561
TI  - Human gastrointestinal nematode infections: are new control methods required?
AB  - Gastrointestinal (GI) nematode infections affect 50% of the human population
      worldwide, and cause great morbidity as well as hundreds of thousands of deaths.
      Despite modern medical practices, the proportion of the population infected with
      GI nematodes is not falling. This is due to a number of factors, the most
      important being the lack of good healthcare, sanitation and health education in
      many developing countries. A relatively new problem is the development of
      resistance to the small number of drugs available to treat GI nematode
      infections. Here we review the most important parasitic GI nematodes and the
      methods available to control them. In addition, we discuss the current status of
      new anthelmintic treatments, particularly the plant cysteine proteinases from
      various sources of latex-bearing plants and fruits.

PMID- 16965562
TI  - Hepatic progenitor cells, stem cells, and AFP expression in models of liver
      injury.
AB  - Adult hepatocytes and liver-cell progenitors play a role in restoring liver
      tissue after injury. For the study of progenitor cells in liver repair,
      experimental models included (a) surgical removal of liver tissue by partial
      hepatectomy; (b) acute injury by carbontetrachloride; (c) acute injury by d
      galactosamine (GalN) and N-nitrosomorpholine (NNM); and (d) chemical
      hepatocarcinogenesis by feeding NNM in low and high doses. Serological and
      immunohistological detection of alpha-fetoprotein gene expression served to
      follow pathways of cellular differentiation. Stem cells were not required in
      models of surgical removal of parenchyma and in carbon tetrachloride intoxication
      of adult hepatocytes. In contrast, regeneration of liver occurred through biliary
      epithelial cells in injuries induced by GalN and NNM. These biliary epithelial
      cells, collectively called oval cells, are most probably derived from the canals
      of Hering. Proliferating bile duct cells reached a level of differentiation with
      reactivation of foetal genes and significant alpha-1-fetoprotein (AFP) synthesis
      signalling a certain degree of retrodifferentiation with potential stemness. Due
      to the same embryonic origin of bile ducts and hepatocytes, biliary epithelium
      and its proliferating progeny (oval cells) have a defined role in liver
      regeneration as a transit and amplification compartment. In their early
      proliferation stage, oval cells were heavily engaged in DNA synthesis
      ([3H]thymidine labelling). Pulse-chase experiments during experimental
      hepatocarcinogenesis exhibited their development into hepatocytes with high risk
      for transformation and leading to foci of altered hepatocytes. Hepatocellular
      carcinomas may arise either from proliferating/differentiating oval cells or from
      adult hepatocytes; both cell types have stem-like properties. AFP-positive and
      AFP-negative carcinomas occurred in the same liver. They may represent random
      clonal origin. The heterogeneity of phenotypic marker (AFP) correlated with a
      process of retrodifferentiation.

PMID- 16965563
TI  - A peritonitis model with low mortality and persisting intra-abdominal abscesses.
AB  - Intra-abdominal abscesses are a potential source of recurrent or residual
      infection after surgical intervention for secondary peritonitis. The development
      of therapies requires a model which combines low mortality with the formation of
      persisting abscesses and which is also suitable to study the local inflammatory
      response. Male Wistar rats were injected intraperitoneally with a mixture of
      sterile rat faeces, increasing doses of E. coli (10(4)-10(8) cfu/ml) and a fixed
      dose of B. Fragilis (10(4) cfu/ml). After one h a laparotomy was performed and
      the peritoneal cavity was debrided. Blood samples were taken under anaesthesia
      after 6 and 24 h. Abdominal fluid samples were collected (by laparotomy) after 24
      and 72 h. The rats were killed after 5 days and the abdomen was inspected for
      abscesses. Mortality was 90% in the two groups with the highest doses of E. coli
      and 30% in those with the two lowest doses. In the latter groups all surviving
      rats but one showed intraabdominal abscesses and bacteremia was encountered
      frequently, especially after 24 h in the 10(5) cfu E. coli group. The groups
      receiving 10(4)-10(6) cfu E. coli showed similar plasma IL-6 concentrations after
      6 h which were lowered significantly after 24 h. No circulating TNF-alpha was
      found. Considerable concentrations of TNF-alpha, IL-6, IL-1beta, and IL-10, were
      found in the peritoneal fluid after 24 h but no differences were observed between
      the contro groups and those receiving 10(4)-10(6) cfu E. coli. At 72 h cytokine
      levels were reduced significantly and remained the highest in the animals dosed
      with 10(6) cfu E. coli. The present model is suitable to study the mechanisms
      involved in, and prevention of, intra-abdominal abscess formation after surgical
      treatment of generalized peritonitis.

PMID- 16965564
TI  - Modulation of inflammatory response in sepsis by proteasome inhibition.
AB  - The Ubiquitin-proteasome system has recently been shown to be involved in the
      regulation of cytokine expression. We tested the hypothesis of whether the in
      vivo administration of proteasome inhibitor MG-132 can modulate cytokine response
      and mortality in sepsis. Sepsis was induced in mice by caecal ligation and
      puncture (CLP). Animals were divided into four groups: control, CLP, CLP and 1
      microg MG-132/g of b.w. intraperitoneally, and CLP and 10 microg MG-132/g of b.w.
      Plasma levels of interleukin (IL)-1, tumour necrosis factor-alpha (TNF-alpha, IL
      6 and IL-10 were determined by ELISA 6 h after the induction of sepsis. CLP
      induced significant increase in plasma levels of all measured cytokines. MG-132
      treatment resulted in lower increase in IL-1, TNF-alpha and IL-10 levels. IL-6
      was not significantly affected. A mortality study revealed prolonged survival in
      MG-132 treated mice. We conclude that MG-132 treatment decreases inflammatory
      response and prolongs survival in the CLP model of sepsis.

PMID- 16965565
TI  - Light cigarette smoke-induced emphysema and NFkappaB activation in mouse lung.
AB  - Light cigarette (LC) exposure is supposed to be less hazardous with a decreased
      incidence of cancer and tobacco-associated diseases. C57BL/6 mouse groups were
      subjected to smoke from 3, 6 or 12 LC for 60 days and compared with mice exposed
      to ambient air (EAA) in order to study lung injury by morphometrical and
      biochemical methods. Bronchoalveolar lavage (BAL) analysis and histology and
      stereology were performed. Tissue from the right lung was used for measuring
      thiobarbituric acid reactive substances (TBARS) and Western blot analysis. One
      way anova was performed followed by the Student-Newman Keuls post-test (P <
      0.05). The cellular content of BAL was 95% alveolar macrophages in all groups
      except in mice exposed to 3 LC, where 23% neutrophils were observed. Emphysema
      was not observed in three and 6 LC, but it was found in 12 LC parallel to
      increased volume density (Vv) of airspaces from 61.0 +/- 0.6 (EAA) to 80.9 +/-
      1.0 (12 LC) and decreased Vv of elastic fibres from 17.8 +/- 0.9 (EAA) to 11.8 +/
      0.6 (12 LC). All exposed groups to LC showed low TBARS levels compared with mice
      EAA. Lung tissue from animals exposed to 12 LC showed decreased tissue inhibitor
      of metalloprotease-2 and increased matrix metalloprotease-12 detection, which
      suggests an imbalance in extracellular matrix (ECM). Increased tumour necrosis
      factor-alpha and nuclear factor-kappaB detection were observed in exposed groups
      to LC when compared with mice EAA. The data suggest that LC is so dangerous to
      lungs as full-flavour cigarettes inducing ECM imbalance and emphysema.

PMID- 16965566
TI  - Acute and chronic hypoxia as well as 7-day recovery from chronic hypoxia affects
      the distribution of pulmonary mast cells and their MMP-13 expression in rats.
AB  - Chronic hypoxia results in pulmonary hypertension due to vasoconstriction and
      structural remodelling of peripheral lung blood vessels. We hypothesize that
      vascular remodelling is initiated in the walls of prealveolar pulmonary arteries
      by collagenolytic metalloproteinases (MMP) released from activated mast cells.
      Distribution of mast cells and their expression of interstitial collagenase, MMP
      13, in lung conduit, small muscular, and prealveolar arteries was determined
      quantitatively in rats exposed for 4 and 20 days to hypoxia as well as after 7
      day recovery from 20-day hypoxia (10% O2). Mast cells were identified using
      Toluidine Blue staining, and MMP-13 expression was detected using monoclonal
      antibody. After 4, but not after 20 days of hypoxia, a significant increase in
      the number of mast cells and their MMP-13 expression was found within walls of
      prealveolar arteries. In rats exposed for 20 days, MMP-13 positive mast cells
      accumulated within the walls of conduit arteries and subpleurally. In recovered
      rats, MMP-13 positive mast cells gathered at the prealveolar arterial level as
      well as in the walls of small muscular arteries; these mast cells stayed also in
      the conduit part of the pulmonary vasculature. These data support the hypothesis
      that perivascular pulmonary mast cells contribute to the vascular remodelling in
      hypoxic pulmonary hypertension in rats by releasing interstitial collagenase.

PMID- 16965567
TI  - Regulation of surfactant protein and defensin mRNA expression in cultured ovine
      type II pneumocytes by all-trans retinoic acid and VEGF.
AB  - Beta-defensins and surfactant proteins are components of the pulmonary innate
      immune system. Their gene expression is regulated by development, hormones,
      growth and immunoregulatory factors. It was our hypothesis that growth and
      differentiation factors such as all-trans retinoic acid (RA) and vascular
      endothelial growth factor (VEGF) may affect expression of selected innate immune
      genes by respiratory epithelial cells. Ovine JS7 cells (alveolar type II
      pneumocytes) were incubated in serum-free Dulbecco's modified Eagle's medium
      (DMEM) complete media that contained: no treatment (negative control), RA (500
      nM), or VEGF (100 ng/ml) for 6, 12 or 24 h incubation. Total RNA was isolated,
      cDNA synthesized, and relative mRNA levels of surfactant protein A (SP-A) and SP
      D, and sheep beta-defensin-1 (SBD-1) were determined by real-time reverse
      transcriptase-polymerase chain reaction (RT-PCR). Cells had significantly
      increased expression of SP-D mRNA at 6 h and 24 h, decreased expression of SP-A
      mRNA at 12 h, and unchanged levels of SBD-1 mRNA after the treatment with RA
      compared with their respective negative controls. VEGF did not alter the
      expression of the three innate immune genes. These findings suggest that SP-A and
      SP-D have different transcription regulation pathways, and that expression of SBD
      1 is not inducible by RA similar to its human homolog HBD-1. The lack of changes
      induced by VEGF treatment suggests that VEGF does not have a direct effect on
      epithelial cells, but may affect gene expression indirectly.

PMID- 16965568
TI  - Transfusion medicine illustrated. Detection of mixed-field agglutination due to
      loss of red cell antigen in hematopoietic malignancy.

PMID- 16965569
TI  - A perspective on transfusion-related acute lung injury two years after the
      Canadian Consensus Conference.

PMID- 16965570
TI  - Is it time to focus on preserving the functionality of red blood cells during
      storage?

PMID- 16965571
TI  - The approach to the patient who refuses blood transfusion.

PMID- 16965572
TI  - Transfusion-related acute lung injury and pulmonary edema in critically ill
      patients: a retrospective study.
AB  - BACKGROUND: Using the recent Consensus Panel recommendations, we sought to
      describe the incidence of transfusion-related acute lung injury (TRALI) and
      transfusion-associated circulatory overload (TACO) in critically ill patients.
      STUDY DESIGN AND METHODS: Consecutive patients at four intensive care units
      (ICUs) who did not require respiratory support at the time of transfusion were
      identified with custom electronic surveillance system that prospectively tracks
      the time of transfusion and onset of respiratory support. Respiratory failure was
      defined as the onset of noninvasive or invasive ventilator support within 6 hours
      of transfusion. Experts blinded to specific transfusion factors categorized the
      cases of pulmonary edema as permeability edema (suspected or possible TRALI) or
      hydrostatic edema (TACO) according to predefined algorithm. In a nested case
      control design, transfusion variables and lung injury risk factors were compared
      between the TRALI cases and controls matched by age, sex, and admission
      diagnosis. RESULTS: There were 8902 units transfused in 1351 patients of whom 94
      required new respiratory support within 6 hours of transfusion. Among 49 patients
      with confirmed acute pulmonary edema, experts identified 7 cases with suspected
      TRALI, 17 patients with possible TRALI, and 25 cases with TACO. The incidence of
      suspected TRALI was 1 in 1271 units transfused; possible TRALI, 1 in 534 per unit
      transfused; and TACO, 1 in 356 per unit transfused. When adjusted for sepsis and
      fluid balance in a stepwise conditional logistic regression analysis, patients
      who developed acute lung injury (suspected or possible TRALI) received larger
      amount of plasma (odds ratio 3.4, 95% confidence interval 1.2-10.2, for each
      liter infused; p = 0.023). CONCLUSION: In the ICU, pulmonary edema frequently
      occurs after blood transfusion. The association between infusion of plasma and
      the development of suspected or possible TRALI may have important implications
      with regards to etiology and prevention of this syndrome.

PMID- 16965573
TI  - The use of autologous blood to improve exercise capacity after total hip
      arthroplasty: a preliminary report.
AB  - BACKGROUND: Venesection of red blood cells in healthy well-trained subjects
      decreased the maximum oxygen uptake parallel with the reduction in hemoglobin
      (Hb) level. Based on the large Hb decrease that is seen after total joint
      surgery, one could expect a decrease in performance as well. The purpose of this
      study was to investigate whether autologous blood enhanced performance on a
      bicycle ergometer in patients after total hip arthroplasty. STUDY DESIGN AND
      METHODS: Nine patients scheduled for elective total hip arthroplasty in an
      accelerated stay program participated in a preoperative autologous blood donation
      (PABD) program. Weeks before the scheduled surgery, patients donated 4 units of
      blood and received standard erythropoietin treatment. Physical fitness was
      assessed during exercise test on a bicycle ergometer. Each patient was matched
      with three previously tested patients. RESULTS: Patients in both groups were 69.0
      years old (range, 66-74 years vs. 61-77 years). None of the patients had relevant
      cardiovascular abnormalities. On average patients received 3.3 units of blood
      because 3 units were not transfused. The PABD group showed a Hb decrease of 0.5 g
      per dL (4%) on the fourth postoperative day versus 4.4 g per dL (31%) in the
      control group. The decline in power output on Day 4 was significantly less in the
      PABD group compared with the control group (t test, p = 0.026). CONCLUSION: From
      this pilot study it can be concluded that correction of the postoperative Hb
      decrease was associated with a lower decrease in maximum power output, compared
      to the control group. On Days 23 and 39, however, the difference in performance
      between the PABD group and control group had disappeared.

PMID- 16965574
TI  - Life, death, and the risk of transfusion: a university hospital experience.
AB  - BACKGROUND: Frequently one encounters donor recruitment statements like ". . .
      about 90 percent of American adults will need at least one blood transfusion in
      the course of a lifetime." To assess the validity of such statements, the
      lifetime transfusion rate of patients dying in our tertiary-care hospital was
      determined. It would be expected that patients dying in a tertiary-care, Level 1
      trauma center university hospital would have one of the highest transfusion
      rates. STUDY DESIGN AND METHODS: A retrospective review of blood bank and
      electronic clinical records was conducted for all patients who expired at our
      institution from January 1, 2004, through December 31, 2004. Stillborn infants
      were excluded from analysis. The rate of transfusion was stratified by age and
      sex. RESULTS: A total of 906 patients expired in 2004 at our institution. Of
      these, 35 were excluded (stillborn infants), leaving 871 patients for analysis.
      After review of blood bank records, 591 patients received blood products (67.9%).
      An additional 27 patients (3.1%) had a possible transfusion at another
      institution as the clinical record indicated complex surgical history. Only 253
      patients (29.0%) did not have a documented transfusion event. Individuals who
      died before the age of 31 had the highest rates of transfusion (p < 0.001,
      Fisher's exact test, two-sided). CONCLUSIONS: The majority of patients who expire
      at our institution have a history of transfusion (67.9%-71.0%). Patients who die
      before the age of 31 have the highest rate of transfusion.

PMID- 16965575
TI  - A functional comparison of mature human dendritic cells prepared in fluorinated
      ethylene-propylene bags or polystyrene flasks.
AB  - BACKGROUND: Fluorinated ethylene-propylene (FEP) bags have been used instead of
      polystyrene (PS) flasks for ex vivo clinical-scale production of human dendritic
      cells (DCs) to facilitate closed-system recovery of these highly adherent cells.
      To assess the impact of DC culture on this nonadherent surface, the function of
      DCs generated in FEP and PS was compared. STUDY DESIGN AND METHODS: Cell yield,
      phenotype, cytokine production, migration, and antigen-presenting activity were
      measured in DCs prepared from peripheral blood monocytes in FEP bags or PS flasks
      with medium supplemented with serum, interleukin (IL)-4, and granulocyte
      macrophage-colony-stimulating factor for 5 days to induce DC differentiation and
      CD40L or poly(I:C) plus interferon-gamma to promote maturation. RESULTS: DCs
      cultured in FEP or PS had comparable cell yield, viability, and CD83 and CCR7
      expression. DCs generated in FEP, however, produced significantly less IL-12 and
      IL-10 during maturation, and differences persisted on rechallenge after harvest.
      FEP-cultured DCs migrated spontaneously or in response to CCR7 ligand more
      actively than PS-cultured DCs, but this difference was not significant. Mature
      DCs prepared in FEP and PS were equipotent in stimulating peptide-specific CD8 T
      cell expansion in vitro. CONCLUSION: FEP- and PS-cultured DCs are similar in
      phenotype and in some functional measures, but FEP markedly reduces DC production
      of IL-12 and IL-10. This phenomenon presumably reflects intracellular changes
      linked to the absence of a surface for firm cell adherence. Given the importance
      of these cytokines in the immune response, these changes could have a significant
      impact on DC function in vivo.

PMID- 16965576
TI  - Antibodies against glutathione S-transferase T1 in non-solid organ transplanted
      patients.
AB  - BACKGROUND: This article describes the presence of antibodies against glutathione
      S-transferase T1 (GSTT1) in a group of patients who never received a solid organ
      graft. These antibodies have been previously detected in liver and kidney
      transplant subjects with donor-recipient mismatch for this enzyme at the genetic
      level. In liver-grafted subjects, the appearance of these antibodies correlated
      with de novo immune hepatitis. STUDY DESIGN AND METHODS: To obtain some insights
      in this phenomenon, the clinical records of these patients were reviewed, and the
      possible causes leading to the production of these antibodies and possible
      clinical consequences were analyzed. RESULTS: The clinical situation of these
      patients was very heterogeneous, but they had in common the need for transfusions
      or a previous pregnancy. GSTT1 antigen is present in red blood cells, liver,
      kidney, and other tissues. Because the presence of the GSTT1-null allele in seven
      of these patients has been demonstrated, it can be hypothesized that both GSTT1
      positive transfusions or pregnancy of a GSTT1-positive fetus could induce these
      antibodies. Because the recipient is allele-null, no adverse effects in the host
      are expected to occur. The longest follow-up (5 years) shows no antibody-derived
      diseases. CONCLUSION: It is concluded that anti-GSTT1 can appear in a context
      different from the previously published alloreactivity after liver and kidney
      transplantation, as a consequence of transfusions and pregnancies. So far, no
      adverse clinical outcomes in our patients have been observed.

PMID- 16965577
TI  - KEL6 and KEL7 genotyping with sequence-specific primers.
AB  - BACKGROUND: Although antibodies to Js(a) and Js(b) are clinically significant,
      reagent-quality anti-Js(a) and anti-Js(b) are not readily available. A sequence
      specific primer-polymerase chain reaction (SSP-PCR) genotyping assay was tested
      that makes use of two single-nucleotide polymorphisms (SNPs) at positions 1910
      and 2019 of KEL. These SNPs distinguish the gene encoding Js(a), KEL6; and Js(b),
      KEL7. STUDY DESIGN AND METHODS: Four primer sets that selectively amplified KEL6
      and KEL7 from genomic DNA were developed. Two sets detected the SNP at bp 1910
      and two sets detected the bp 2019 SNP. KEL6 and KEL7 genotyping and Js(a) and
      Js(b) phenotyping results were compared among 64 subjects. RESULTS: The SSP-PCRs
      were specific for KEL6 and KEL7 when testing DNA for three donors of known Js
      phenotype: Js(a+b-), Js(a-b+), and Js(a+b+). Genotyping results for the 1910 SNP
      were identical to the phenotyping results in all 64 subjects, but for the 2019
      SNP, the genotyping and phenotyping results were identical for only 49 subjects.
      In 12 subjects with the Js(a-b+) phenotype, the 2019 SNP was heterozygous KEL6,
      KEL7; in 2 with Js(a-b+) and in 1 with Js(a+b+), the 2019 SNP was homozygous
      KEL6. CONCLUSION: KEL 2019-bp SNP does not always correlate with the Js phenotype
      owing to the presence of an atypical KEL gene with a KEL7 polymorphism at 1910
      and a KEL6 polymorphism at 2019. The KEL polymorphism at 2019 is silent and this
      allele yields a Js(a-b+) phenotype. Only analysis of the 1910-bp SNP can be used
      to genotype KEL6 and KEL7.

PMID- 16965578
TI  - Gene frequencies of the HNA-4a and -5a neutrophil antigens in Brazilian persons
      and a new polymerase chain reaction-restriction fragment length polymorphism
      method for HNA-5a genotyping.
AB  - BACKGROUND: The HNA-4a (Mart) and HNA-5a (Ond) antigens are polymorphic variants
      of alpha(M) (CD11b) and alpha(L) (CD11a) subunits of the beta(2)-integrin, and
      are associated with single nucleotide polymorphisms (SNP) leading to amino acid
      dimorphisms. HNA-4a has been linked to alloimmune neonatal neutropenia, but the
      HNA-5a clinical significance is unclear. STUDY DESIGN AND METHODS: Using a
      polymerase chain reaction (PCR) with sequence-specific primers, the frequency of
      HNA-4a among 121 Brazilian blood donors and 114 Amazon Indians was determined. A
      PCR-restriction fragment length polymorphism (RFLP) method for HNA-5a genotyping
      was developed, and the gene frequencies of this antigen were determined among 123
      blood donors and 114 Indians. To validate the genotyping method, the amplified
      DNA from six previously obtained samples (two of each genotype) was sequenced.
      RESULTS: The HNA-4a (+/+), HNA-4a (+/-), and HNA-4a (-/-) genotype frequencies of
      blood donors (0.686, 0.273, 0.041) and Indians (1.000, 0.000, 0.000) were
      different (p < 0.01). The frequencies of HNA-5a (+/+), HNA-5a (+/-), and HNA-5a (
      /-) genotypes among blood donors (0.512, 0.399, 0.089) and Indians (0.746, 0.219,
      0.035) also differed (p < 0.01). Sequencing demonstrated concordance with PCR
      RFLP genotyping in all six evaluated samples. CONCLUSION: Comparing to another
      populations, Brazilians present a higher frequency of HNA-4a-negative allele,
      suggesting that Brazilians would be more susceptible to HNA-4a alloimmunization.
      Moreover, the distribution of the HNA-4 alleles observed in Amazon Indians is
      quite similar to that reported among Koreans. Besides that, a new effective and
      efficient HNA-5a genotyping technique is now available for population studies.

PMID- 16965579
TI  - Optimal prewarming conditions for Rh antibody testing.
AB  - BACKGROUND: Although prewarming (PW) can reduce the confounding agglutination of
      cold-reactive antibodies when testing for warm-reactive antibodies, PW also can
      adversely affect the detection of warm-reactive antibodies. This study was
      conducted to determine PW conditions that optimized Rh antibody detection. STUDY
      DESIGN AND METHODS: In 38 plasma samples with Rh system antibodies detected by
      any of four methods, and in 8 other samples with cold-reactive antibodies,
      reactivity was assessed by titer and score. RESULTS: PW to 37 degrees C often
      reduced reaction scores by all methods especially the low-ionic-strength saline
      indirect antiglobulin test and bromelin methods. In analyses warming red blood
      cell (RBC) suspensions or plasma, the reaction scores were decreased only when
      the RBC suspension was warmed, suggesting that RBC PW decreased Rh antibody
      reactivity. The warming period ranging from 5 to 30 minutes all decreased Rh
      system reaction scores, an effect persisting up to 120 minutes. At lower
      temperatures (27, 30, and 33 degrees C), numbers of samples showing decreased
      reaction score for Rh system antibodies decreased in a temperature-dependent
      manner. Testing at 27 degrees C also permitted some agglutination involving cold
      reactive antibodies, whereas higher temperatures successfully suppressed their
      agglutination. CONCLUSION: PW at 30 degrees C minimizes problems in accurately
      detecting Rh system antibodies.

PMID- 16965580
TI  - Recipient inflammation affects the frequency and magnitude of immunization to
      transfused red blood cells.
AB  - BACKGROUND: Most alloantigens on transfused red blood cells (RBCs) are weakly
      immunogenic, with only a 2 to 6 percent overall immunization rate even in
      patients receiving multiple transfusions. Although recipient genetics may
      contribute to responder and/or nonresponder status, in most cases HLA type does
      not predict humoral response to RBC antigens. In contrast, rates of
      alloimmunization do correspond to the underlying disease status of transfusion
      recipients, suggesting that acquired host factors may play an important role. In
      this context, it was hypothesized that the inflammatory status of a transfusion
      recipient would influence immunization to transfused RBCs. STUDY DESIGN AND
      METHODS: A novel murine model for alloimmunization to RBC antigens was developed
      with the mHEL mouse, which expresses hen egg lysozyme (HEL) as a model blood
      group antigen. Leukoreduced mHEL RBCs were transfused into wild-type recipient
      mice, and anti-HEL responses were monitored. To test the stated hypothesis, some
      recipient animals were injected with polyinosinic polycytidylic acid (poly(I:C)),
      a synthetic double-stranded RNA molecule that induces viral-like inflammation.
      RESULTS: Similar to the immunogenicity of most RBC antigens in humans,
      transfusion of mHEL RBCs into uninflamed mice was only a weak immunogen. In
      contrast, poly(I:C)-treated mice had a significant increase in both the frequency
      and the magnitude of alloimmunization to the mHEL antigen. CONCLUSIONS: These
      findings demonstrate that recipient inflammation with poly(I:C) significantly
      enhances humoral immunization to transfused alloantigens in a murine model.
      Moreover, these data suggest that the inflammatory status of human transfusion
      recipients may regulate the immunogenicity of transfused RBCs.

PMID- 16965581
TI  - Case report and literature review: transient Inab phenotype and an agglutinating
      anti-IFC in a patient with a gastrointestinal problem.
AB  - BACKGROUND: The Inab phenotype is a rare deficiency of all Cromer antigens. These
      antigens are carried on the decay-accelerating factor (DAF, CD55) molecule that
      is attached to the red blood cell (RBC) membrane by a
      glycosylphosphatidylinositol (GPI) anchor. Although typically inherited, an
      acquired and transient form of the Inab phenotype also exists. A patient with the
      triad of transient Inab phenotype, a direct-agglutinating anti-IFC, and
      gastrointestinal (GI) abnormalities is reported. CASE REPORT: An 18-month-old boy
      with gastroesophageal reflux disease requiring a feeding tube, milk and soy
      intolerance, and severe growth retardation, as well as vision and hearing
      deficits from cytomegalovirus infection, was identified when pretransfusion
      testing revealed a potent panagglutinin (titer > 2000 at 4 degrees C). This
      antibody did not react with Dr(a-) and IFC RBCs, and the autocontrol was
      negative. The patient's RBCs lacked CD55 by flow cytometric techniques but had
      normal levels of CD59 and antigens such as Yt(a) and Emm, carried on GPI-linked
      proteins, thus excluding paroxysmal nocturnal hemoglobinuria. Several months
      after initial detection, the anti-IFC was virtually undetectable and his cells
      reacted weakly with anti-IFC, anti-Dr(a), and anti-CD55. RBCs from the
      propositus' parents and brother demonstrated normal CD55 and CD59 expression.
      CONCLUSION: This is the first example of a direct-agglutinating anti-IFC. The
      cause of the transient depression in CD55 protein (and thus Cromer system
      antigens) and appearance of anti-IFC remains unknown, as does the relationship
      between the patient's GI system abnormalities and these serologic findings.

PMID- 16965582
TI  - Storage of red blood cells with improved maintenance of 2,3-bisphosphoglycerate.
AB  - BACKGROUND: During storage, red blood cells (RBCs) rapidly lose 2,3
      bisphosphoglycerate (2,3-DPG) leading to an increase in the affinity for O(2) and
      a temporary impairment of O(2) transport. Recent clinical evaluations indicate
      that the quality of transfused RBCs may be more important for patient survival
      than previously recognized. STUDY DESIGN AND METHODS: Glucose-free additive
      solutions (ASs) were prepared with sodium citrate, sodium gluconate, adenine,
      mannitol, and phosphates at high pH, a solution that can be heat-sterilized. CP2D
      was used as an anticoagulant. Additional CP2D was added to the AS to supply
      glucose. RBCs were stored at 4 degrees C and assayed periodically for
      intracellular pH (pHi), extracellular pH, glucose, lactate, phosphate, ATP, 2,3
      DPG, hemolysis, and morphology. RESULTS: Storage in 175 mL of the chloride-free,
      hypotonic medium at a hematocrit (Hct) level of 59 to 60 percent resulted in an
      elevated pHi and the maintenance of 2,3-DPG at or above the initial value for 2
      weeks without loss of ATP. The addition of 400 mL of storage solution followed by
      centrifugation and removal of 300 mL of excess solution to a Hct level of 60 to
      66 percent further reduced the chloride concentration, resulting in the
      maintenance of 2,3-DPG for 4 weeks. Hemolysis was at 0.1 percent at 6 weeks.
      CONCLUSION: Improvements in the maintenance of 2,3-DPG were achieved with 175 mL
      of a chloride-free storage solution with familiar additives at nontoxic
      concentrations to increase pHi. Adding, instead, 400 mL of storage solution
      followed by the removal of 300 mL reduced the chloride concentration, increasing
      the pHi and extending the maintenance of 2,3-DPG to 4 weeks.

PMID- 16965583
TI  - Mirasol PRT treatment of donor white blood cells prevents the development of
      xenogeneic graft-versus-host disease in Rag2-/-gamma c-/- double knockout mice.
AB  - BACKGROUND: Mirasol PRT (Navigant Biotechnologies) treatment utilizes exposure to
      light in the presence of riboflavin to introduce irreparable lesions to nucleic
      acids thereby inhibiting pathogen and WBC replication. The ability of Mirasol PRT
      treated mononuclear cells (MNCs) to generate xenogeneic graft-versus-host disease
      (GVHD) responses was used to model transfusion-associated GVHD (TAGVHD). STUDY
      DESIGN AND METHODS: Pairs of human MNCs from five different individual donors
      that had or had not received Mirasol PRT treatment and contained 30 x 10(6) CD3+
      cells were injected intraperitoneally into sublethally irradiated (350 cGy) Rag2(
      /-)gamma c(-/-) double-knockout mice. Recipient mice were weighed and observed
      regularly and euthanized when they exhibited symptoms of GVHD or at termination
      of the experiment. Recipient lymphoid compartments were collected and phenotyped
      for the presence of human lymphoid cells. The presence of human cytokines and/or
      immunoglobulins in the recipient plasma was also used to detect the presence of
      human cells. RESULTS: Twelve of 14 mice injected with untreated cells developed
      xenogeneic GVHD, whereas 0 of 14 mice injected with Mirasol PRT-treated cells
      developed xenogeneic GVHD. End-stage xenogeneic GVHD in the recipients of
      untreated cells was characterized by the presence of splenic human cytolytic CD4+
      and CD8+ cells, with high levels of interferon-gamma, interleukin-10, and
      xenoreactive antibodies in the plasma. CONCLUSION: Mirasol PRT treatment of the
      donor MNCs abolished xenogeneic GVHD responses, indicating that the use of
      Mirasol PRT treatment of blood products should prevent the development of TAGVHD.

PMID- 16965584
TI  - Storage duration and white blood cell content of red blood cell (RBC) products
      increases adhesion of stored RBCs to endothelium under flow conditions.
AB  - BACKGROUND: Adherence of red blood cells (RBCs) to vascular endothelium impairs
      blood flow and decreases oxygen delivery. Although RBCs may be stored for up to
      42 days before transfusion under current blood banking guidelines, little is
      known of how changes to RBCs during storage may affect their adherence
      properties. The influence of RBC product storage time and white blood cell (WBC)
      burden on the adherence of RBCs for transfusion to vascular endothelium under
      conditions of continuous flow was investigated in this study. STUDY DESIGN AND
      METHODS: RBC samples were collected from nonleukoreduced (S-RBC), buffy coat-poor
      (BCP-RBC), and leukofiltered (LF-RBC) products at fixed time points during
      storage. Samples were perfused, at controlled shear stress and temperature,
      across a confluent endothelial cell (EC) monolayer with a parallel-flow chamber
      mounted to an inverted microscope. RBC-EC interactions were recorded with a
      digital camera attached to the microscope. RESULTS: The number of RBCs adhering
      to the EC layer increased significantly with storage time in all RBC products;
      however, WBC reduction delayed this increase. LF-RBCs were also significantly
      less adherent than S-RBC or BCP-RBC products on Day 1 of storage (p < 0.05). The
      strength of RBC attachment to vascular endothelium was significantly stronger in
      S-RBC products compared to BCP-RBC and LF-RBC products. CONCLUSION: Our findings
      indicate that product storage time and WBC burden increase the number and
      strength of adhesion of RBCs to vascular endothelium. These results may lead to
      greater understanding of the interaction of transfused RBCs with recipient
      endothelium and the biologic consequences of this adherence.

PMID- 16965585
TI  - Clinical experience with a new apheresis filter that specifically depletes ABO
      blood group antibodies.
AB  - BACKGROUND: Although living kidney donors are increasingly being used, in most
      centers, 30 to 40 percent of potential donors are being turned down due to ABO
      mismatch. A protocol for ABO-mismatched kidney transplantation without
      splenectomy and with antigen-specific adsorption of ABO antibodies instead of
      nonspecific plasmapheresis was therefore designed. STUDY DESIGN AND METHODS: The
      immunosuppressive protocol used at the Department of Transplantation Surgery,
      Karolinska University Hospital, Stockholm, Sweden, together with relevant
      clinical data for 11 of the studied patients, have been described previously. The
      protocol called for immunoadsorption of ABO antibodies on Days -6, -5, -2, and -1
      and on Days +2, +5, and +8. Patient plasma was recirculated through a new
      apheresis filter, the Glycosorb ABO column (Glycorex Transplantation AB),
      containing synthetic terminal trisaccharide A or B blood group antigen linked to
      a Sepharose matrix. RESULTS: Since 2001, 15 patients, including 2 infants, have
      been successfully transplanted with ABO-mismatched kidneys from living donors.
      The donor-recipient blood groups were A1-O (n = 5), A2-O (n = 2), B-O (n = 4), B
      A (n = 2), and A1B-B (n = 2). ABO antibody titers at transplantation did not
      exceed immunoglobulin G 4 or immunoglobulin M 4 levels. No humoral rejections and
      no late rebound of ABO antibodies were observed. No adverse effects related to
      immunoadsorption treatment have been recorded. CONCLUSION: It is concluded that
      ABO-mismatched kidney transplantations can be successfully performed without
      splenectomy and that ABO antibodies can be effectively and safely depleted with
      the Glycosorb ABO column.

PMID- 16965586
TI  - Arsine toxicity treated with red blood cell and plasma exchanges.
AB  - BACKGROUND: Acute toxicity due to inhalation of arsine gas (AsH(3)) has no known
      antidote. Exchange transfusion may be beneficial, and dialysis is often required
      because arsine may cause acute intravascular hemolysis and renal failure. A
      patient with arsine toxicity has recently been treated by both red blood cell
      exchange (RBC-E) and plasma exchange (PE) therapy and our experience is reported.
      CASE REPORT: A 46-year-old man was accidentally and unknowingly exposed to arsine
      gas while observing an industrial procedure. Within 6 hours he developed fatigue,
      nausea, vomiting, and tingling in his extremities and voided dark urine. He
      quickly developed renal failure secondary to acute arsine toxicity (arsenic
      level, 1250 microg/L). Laboratory findings were a hematocrit level of 24 percent;
      blood urea nitrogen and creatinine, 84 and 5.5 mg per dL, respectively;
      bilirubin, 9.1 mg per dL; indirect bilirubin, 6.8 mg per dL; haptoglobin, less
      than 6 (normal, 30-200); and lactic dehydrogenase, 10,413 units per L (normal,
      265-580). An emergent 1-vol RBC-E transfusion by continuous-flow method revealed
      dramatic black, grossly hemolyzed plasma. After two additional RBC-E and two PE
      and daily hemodialysis, he completely recovered over the course of 1 month.
      CONCLUSION: Patients with arsine toxicity resulting in intravascular hemolysis
      should receive RBC-E as soon as possible. In addition, PE may be beneficial in
      removing the components of RBC lysis and further reducing arsenic levels.

PMID- 16965587
TI  - Development of models and detection methods for different forms of
      cytomegalovirus for the evaluation of viral inactivation agents.
AB  - BACKGROUND: Cytomegalovirus (CMV) is transmitted by transfusion of infected blood
      products and can cause serious diseases in specific risk groups. CMV can be
      present in infected blood as cell-free virus (CFV), cell-associated actively
      replicating virus (CAV), and cell-associated latent virus (LV). STUDY DESIGN AND
      METHODS: In vitro models for all three infectious forms of CMV and virus
      detection assays based on both tissue culture and polymerase chain reaction (PCR)
      were developed. The utility of the CMV model systems and assays were tested by
      validation studies of a novel pathogen inactivation agent, PEN110, for red blood
      cells. RESULTS: Reproducible high titers of CFV and CAV were obtained by
      optimized tissue culture techniques for CMV-infected MRC-5 cells. An LV model was
      obtained with CMV-infected THP-1 cells and reactivation of virus replication by
      phorbol ester treatment. The model systems showed that PEN110 treatment is
      effective against all three forms of CMV as measured by tissue culture-based
      infectivity assays and a long-range PCR method specific for detection of damage
      to CMV viral DNA. CONCLUSION: This study describes model systems to the relevant
      forms of CMV in blood and detection assays that can be used to evaluate the
      efficacy of viral inactivation agents.

PMID- 16965588
TI  - Absence of detectable viremia in plasma and peripheral blood mononuclear cells
      from smallpox vaccinees: implications for blood safety.
AB  - BACKGROUND: Mass smallpox vaccination with live vaccinia virus has been
      considered as a preventive measure to counter bioterrorism involving smallpox.
      This has raised concerns about the possibility of vaccinia virus being
      transmitted from vaccinated blood donors to recipients. The results of this study
      could be used to define an appropriate deferral period for blood donors
      (vaccinated against smallpox) to ensure safety of the blood supply. STUDY DESIGN
      AND METHODS: A procedure was developed to culture vaccinia virus from plasma and
      peripheral blood mononuclear cells (PBMNCs) of vaccinees enrolled in three
      smallpox vaccine clinical trials. A total of 665 plasma and PBMNC samples were
      obtained from 95 vaccinated subjects. RESULTS: Vaccinia viremia was not detected
      by virus culture from plasma and PBMNC samples of healthy vaccinees 3 to 56 days
      after vaccination under our assay conditions. Plasma viremia assay had a
      sensitivity of approximately 66 plaque-forming units per mL with a Vero cell
      culture assay. CONCLUSION: The results of this study present evidence that in the
      case of mass vaccination, the risk of transmission of vaccinia virus by blood
      transfusion would likely be low.

PMID- 16965589
TI  - Effects of transfusion on human erythrovirus B19-susceptible or -infected
      pediatric recipients in a genotype 3-endemic area.
AB  - BACKGROUND: Human erythrovirus (parvovirus) B19 is transmitted by transfusion of
      blood, blood components, and plasma derivatives and is resistant to most viral
      inactivation methods. B19 genotype 3 is prevalent in Ghana, and no related
      clinical information is available. STUDY DESIGN AND METHODS: This study assessed
      the transmission of B19 genotype 3 by transfusion and the potential effect of
      transfused B19 antibodies in viremic recipients. Immunological aspects of B19
      genotype 3 infection in children mainly transfused for acute malarial anemia were
      examined. Molecular and serologic methods adapted to genotype 3 were developed
      and used. RESULTS: Among 114 donor-recipient pairs from Ghana, two donations
      contained B19 DNA and specific antibodies, and no evidence of transmission was
      found. B19 immunoglobulin G (IgG)-containing whole blood was transfused to 14 B19
      DNA-positive recipients. Three recipients with detectable levels of IgG to B19
      failed to clear viremia 1 to 2.3 months after transfusion. Ten recipients without
      IgG to VP2 before transfusion cleared the virus but failed to develop an immune
      response to B19 within 1 to 2 months after transfusion. Only 1 patient who
      received little specific IgG by transfusion produced detectable antibodies.
      CONCLUSION: Low levels of B19 genotype 3 DNA associated with specific IgG are not
      infectious by transfusion. Viral clearance and apparent down regulation of immune
      response to B19 may be related to removal of the viral antigens by transfused
      antibodies and/or immunomodulatory effect of transfusion.

PMID- 16965590
TI  - Prospective comparison of high-dose plateletpheresis with the latest apheresis
      systems on the same donors.
AB  - BACKGROUND: To improve productivity of automated platelet (PLT) collection, the
      industry has introduced new instruments or modifications to existing equipment.
      STUDY DESIGN AND METHODS: With the same 8 donors for double (DDC) and triple-dose
      PLT collection (TDC), the Baxter Amicus (AM), the Haemonetics MCS Plus (MCS+),
      and the Gambro Trima Accel (TA) were evaluated focusing on yield, duration, and
      citrate donor load. Target endpoints were set at 5.5 x 10(11) to 6.0 x 10(11)
      PLTs (DDC) and 7.5 x 10(11) to 8.0 x 10(11) PLTs (TDC) in up to 100 and 120
      minutes' donation time, respectively. RESULTS: TA was the most efficient system
      (74.5 +/- 3.9%) with significant differences from AM (71.1 +/- 3.9%; p = 0.028)
      and MCS+ (64.0 +/- 7.7%; p = 0.002). TA had advantages over AM for collection
      rate (10.9 x 10(9) +/- 2.2 x 10(9) vs. 10.1 x 10(9) +/- 1.5 x 10(9) PLTs/min; p =
      0.382), whole blood processed (3928 +/- 611 mL vs. 4219 +/- 727 mL; p = 0.382),
      and time to obtain an established standard dose (TSD 2.5(EU), 30.2 +/- 5.6 vs.
      37.7 +/- 5.5 min; TSD 3.5(US), 42.2 +/- 7.8 min vs. 52.7 +/- 7.7 min; p = 0.015),
      whereas AM was slightly superior in PLT yield (2.81 x 10(11) +/- 0.21 x 10(11)
      vs. 2.76 x 10(11) +/- 0.31 x 10(11)/unit; p = 0.645). Owing to the lowest draw
      (42.3 +/- 3.2 mL/min; p < 0.001) and collection rates (6.0 x 10(11) +/- 1.5 x
      10(11)/min; p = 0.021), MCS+ was the slowest significantly (p < 0.001) but
      compensated with fewer citrate reactions owing to lower citrate infusion rates
      (0.78 +/- 0.11 mL/min/L; p = 0.028). CONCLUSION: High-dose plateletpheresis was
      performed efficiently and safely with all three instruments. AM had advantages in
      PLT yield, and MCS+, in donor comfort. TA was the fastest in obtaining an
      established standard dose and, because of this advantage, the machine with the
      highest practical impact in routine use.

PMID- 16965591
TI  - Blood volume regulation in donors undergoing intermittent-flow plasmapheresis
      involving a high extracorporeal blood volume.
AB  - BACKGROUND: Intermittent-flow plasmapheresis (IFP) often involves a large
      extracorporeal blood volume (ECV) of donors during donation. Depending on
      equipment and donor characteristics, ECV can exceed 20 percent of a donor's blood
      volume (BV). It was the aim of this study to delineate mechanisms of BV
      regulation associated with these volume shifts. STUDY DESIGN AND METHODS:
      Parameters of BV regulation were recorded in 60 donors (30 men, 30 women)
      undergoing IFP, who were randomly selected after stratification for sex and BV.
      Shock index (SI), stroke volume (SV), cardiac index (CI), and thoracic fluid
      content (TFC) were determined at the beginning of the procedure and when maximum
      ECV (ECV(max)) was reached with noninvasive techniques. In a control
      investigation, donors were kept in reclined position for the duration of an IFP
      session without actually donating. RESULTS: SI increased significantly during IFP
      (+0.18; p < 0.0001). SV decreased significantly (-14.3 mL/stroke; p < 0.0001). CI
      did not decrease significantly (-0.07 L/min/m(2) body surface area; p = 0.33).
      Preservation of CI was due to a significant rise in heart rate (+13.4 beats/min;
      p < 0.0001). TFC decreased significantly during IFP (-0.77 kOmega(-1); p <
      0.0001), indicating the development of an intravascular volume deficit. The
      changes of SI, heart rate, and TFC weakly correlated with ECV(max). CONCLUSION:
      The hemodynamic response during IFP is consistent with a hypovolemic challenge of
      the donors and is sufficient to maintain cardiac function. ECV(max) during
      donation does not reliably predict the degree of hypovolemic stress, as long as
      it remains below 20 percent. This might warrant reevaluation of collection limits
      based on ECV(max).

PMID- 16965592
TI  - Increased iron absorption during autologous blood donation supported by
      recombinant human erythropoietin therapy.
AB  - BACKGROUND: Recombinant human erythropoietin (rHuEPO) therapy improves the
      success of autologous blood (AB) donation programs before elective surgery. The
      aim of this study was to evaluate iron absorption during an AB donation program
      with or without rHuEPO. STUDY DESIGN AND METHODS: Thirty-two patients were
      randomly assigned among placebo (Group 1) or 300 (Group 2) or 600 UI per kg
      rHuEPO (Group 3) on the first, second, and third donation visits. All patients
      also received daily oral iron (200 mg Fe(+)). RESULTS: The number of units
      collected in Group 3 was higher than in Group 1 (4.6 +/- 0.5 vs. 3.6 +/- 0.8
      units; p < 0.01). Red blood cell (RBC) production increased in a rHuEPO dose
      dependent manner. With rHuEPO, the RBC volume collected per unit presented a
      lower decrease with number of donated units than with placebo and was similar to
      that of homologous blood units. Storage iron did not influence the number of
      units collected, whereas circulating mobilizable iron was the limiting factor.
      Oral iron absorption increased in a rHuEPO dose-dependent manner (12-fold with
      600 UI/kg rHuEPO) and was proportional to erythropoietic activity. CONCLUSION:
      rHuEPO does not only improve the number of AB units collected but also their
      quality. Storage iron cannot meet marrow iron requirements, but rHuEPO strongly
      increased oral iron absorption in a dose-dependent fashion through stimulation of
      erythropoietic activity.

PMID- 16965593
TI  - Transfusion-transmitted viral infections: building bridges to transfusion
      medicine to reduce risks and understand epidemiology and pathogenesis.

PMID- 16965594
TI  - Leishmania: risk to the blood supply.
AB  - Leishmania infection is most often transmitted to humans via the bite of the
      phlebotomine sandfly, but transmission of Leishmania by transfusion has also been
      reported. There has been a huge increase in the incidence of cutaneous and
      visceral leishmaniasis in Iraq and Afghanistan. The deployment of US troops to
      these countries and published case reports of transmission to soldiers in endemic
      areas, by transfusion to infants with immature immune systems, and to individuals
      immunocompromised by disease or immunosuppressive therapy beckon a reexamination
      of blood donor deferral procedures. The length of the ongoing military conflict
      and the nature of exposure indicate that prior decisions regarding blood donor
      deferral made during the first Gulf War may no longer apply. Operation Iraqi
      Freedom and Operation Enduring Freedom present a much greater Leishmania threat
      than did Operation Desert Storm. Because most transmission by transfusion occurs
      in endemic areas, and visceral infection is asymptomatic in healthy individuals
      such as blood donors, it is difficult to determine the absolute risk of
      transmission by transfusion, but review of the literature provides many clues as
      to the appropriate measures to be taken for blood donor deferral.

PMID- 16965595
TI  - Recipient-derived clots in red blood cells during transfusion.

PMID- 16965596
TI  - Serologic testing for human T-lymphotropic virus-3 and -4.

PMID- 16965597
TI  - Inactivation of parvovirus B19 and model viruses in factor VIII by dry heat
      treatment at 80 degrees C.

PMID- 16965599
TI  - On the immunologic basis of Rh immune globulin (anti-D) prophylaxis.

PMID- 16965600
TI  - High expression of insulin-like growth factor binding protein-3 is correlated
      with lower portal invasion and better prognosis in human hepatocellular
      carcinoma.
AB  - Insulin-like growth factor binding protein-3 (IGFBP-3) modulates cell
      proliferation of various cancer cell types. However, it remains unclear how IGF
      IGFBP-3-signaling is involved in growth and progression of hepatocellular
      carcinoma (HCC). The aim of the present study was to evaluate the role of IGFBP-3
      in HCC. Type 1 receptor for IGF (IGF-1R) was expressed at various levels in the
      seven lines examined, but IGF-2R was not expressed. Of the seven lines, the
      growth of HAK-1B, KIM-1, KYN-2 and HepG2 cells was stimulated in a dose-dependent
      manner by the exogenous addition of IGF-I or IGF-II, but the HAK-1A, KYN-1 and
      KYN-3 cell lines showed no growth. Exogenous addition of IGFBP-3 markedly blocked
      IGF-I and IGF-II-stimulated cell growth of KYN-2 and HepG2 cells, and moderately
      stimulated that of KIM-1 and HAK-1B cells, but no growth of the KYN-1, KYN-3 and
      HAK-1A cell lines was observed. IGF-I enhanced the phosphorylation of IGF-1R, Akt
      and Erk1/2 in KYN-2 cells, and coadministration of IGFBP-3 blocked all types of
      activation by IGF-I investigated here. In contrast, no such activation by IGF-I
      was detected in KYN-3 cells. IGFBP-3 also suppressed IGF-I-induced cell invasion
      by KYN-2 cells. Moreover, we were able to observe the apparent expression of
      IGFBP-3 in KYN-3 cells, but not in the other six cell lines. Furthermore reduced
      expression of IGFBP-3, but not that of IGF-1R, was significantly correlated with
      tumor size, histological differentiation, capsular invasion and portal venous
      invasion. Low expression of IGFBP-3 was independently associated with poor
      survival. IGFBP-3 could be a molecular target of intrinsic importance for further
      development of novel therapeutic strategy against HCC.

PMID- 16965601
TI  - Pharmacogenetic impact of polymorphisms in the coding region of the UGT1A1 gene
      on SN-38 glucuronidation in Japanese patients with cancer.
AB  - Pharmacogenetic testing for UDP-glucuronosyltransferase (UGT) 1A1*28, a promoter
      variant of the UGT1A1 gene, is now carried out clinically to estimate the risk of
      irinotecan-associated toxicity. We studied the clinical significance of UGT1A1*6
      and UGT1A1*27, two variants in exon 1 of the UGT1A1 gene that are found mainly in
      Asians. The study group comprised 46 Japanese patients who received various
      regimens of chemotherapy including irinotecan at doses from 50 to 180 mg/m(2).
      Pharmacogenetic relationships were explored between the UGT1A1 genotype and the
      ratio of the area under the plasma concentration-time curve (AUC) of the active
      metabolite of irinotecan (SN-38) to that of SN-38 glucuronide (SN-38G), used as a
      surrogate for UGT1A1 activity (AUC(SN-38)/AUC(SN-38G)). No patient was homozygous
      for UGT1A1*28, and none had UGT1A1*27. Two were heterozygous for UGT1A1*28. Two
      were homozygous and 15 heterozygous for UGT1A1*6, all of whom were wild type with
      respect to UGT1A1*28. Two patients were simultaneously heterozygous for UGT1A1*28
      and UGT1A1*6, present on different chromosomes. The other 25 patients had none of
      the variants studied. The two patients simultaneously heterozygous for UGT1A1*28
      and UGT1A1*6 and the two patients homozygous for UGT1A1*6 had significantly
      higher AUC(SN-38)/AUC(SN-38G) ratios than the others (P = 0.0039). Concurrence of
      UGT1A1*28 and UGT1A1*6, even when heterozygous, altered the disposition of
      irinotecan remarkably, potentially increasing susceptibility to toxicity.
      Patients homozygous for UGT1A1*6 should also be carefully monitored. UGT1A1
      polymorphisms in the coding region of the UGT1A1 gene should be genotyped in
      addition to testing for UGT1A1*28 to more accurately predict irinotecan-related
      toxicity, at least in Asian patients.

PMID- 16965602
TI  - Hypomethylation of the protein gene product 9.5 promoter region in gallbladder
      cancer and its relationship with clinicopathological features.
AB  - Protein gene product 9.5 (PGP9.5) is a neurospecific peptide that removes
      ubiquitin from ubiquitinated proteins and prevents them being targeted for
      degradation by proteosomes. Its expression is a potential marker of non-small
      lung cancer, invasive colorectal cancer and esophageal squamous cell carcinoma.
      Gallbladder (GB) cancer is the most common malignant tumor of the biliary tract
      and is usually associated with gallstone disease, a late diagnosis,
      unsatisfactory treatment and a poor prognosis. To understand the role of PGP9.5
      in GB cancer, we examined the methylation status of its promoter and its
      expression in surgical biopsy samples. Formalin-fixed, paraffin-embedded tumors
      and non-neoplastic GB tissues (22 carcinomas, eight adenomas, 26 normal
      epithelia) were collected from patients who had undergone surgical resection. The
      methylation status of the promoter region of the PGP9.5 gene was determined by
      methylation-specific polymerase chain reaction, and the expression of PGP9.5 was
      examined by immunohistochemistry using tissue microarrays. PGP9.5 promoter was
      methylated in 84.6% (22/26) of normal GB epithelium, 37.5% (3/8) of adenomas and
      27.2% (6/22) of carcinomas. Most tumors with an unmethylated promoter exhibited
      positive staining for PGP9.5 in epithelial and neoplastic cells, but no PGP9.5
      expression was observed in normal epithelia or in tumor tissues with a methylated
      promoter. No correlation was found between promoter hypomethylation of PGP9.5 and
      clinicopathological findings (i.e. age, sex, histological type or grade, N
      status, invasion depth or tumor stage) whereas PGP9.5 hypomethylation was found
      to be inversely correlated with the presence of a gallstone (P = 0.015). These
      results suggest that PGP9.5 promoter hypomethylation could be a reliable marker
      for GB cancer and that DNA hypomethylation might play an important role in re
      expression of the PGP9.5 gene in GB cancer.

PMID- 16965603
TI  - Preattentively grouped tones do not elicit MMN with respect to each other.
AB  - To promote preattenive grouping of two sets of tones, one set of tones with a
      combination of frequency and ear of delivery was intermixed with another set of
      tones with a different combination of frequency and ear of delivery. The ERPs
      elicited by tones delivered to one ear that were preceded by three or four tones
      delivered in a row to the other ear were associated with an enhanced N1, due to
      the changes in frequency and ear of delivery with respect to the immediately
      preceding tones. However, no mismatch negativity (MMN) was obtained, even though
      these tones differed from the previious tones on the two dimensions of frequency
      and ear of delivery. The data were interpreted to signify that preattentively
      grouped sets of tones do not elicit MMN with respect to one another. This implies
      that once acoustic input has been preattentively grouped, the MMN system is
      dedicated to detecting changes that occur within but not between preattentively
      grouped stimuli.

PMID- 16965604
TI  - Electromagnetic brain activity evoked by affective stimuli in schizophrenia.
AB  - Schizophrenia is typically associated with cognitive deficits, but symptoms also
      point to alterations in the processing of affective material, with potential
      impact on behavioral performance. This impact may unfold on multiple time scales,
      but initial processing of rapidly unfolding social cues may be particularly
      important. MEG-assessed regional brain activity associated with the capacity to
      process the emotional content of rapid visual stimuli (3/s) was examined in 12
      individuals with schizophrenia and 12 matched controls. Patients showed less
      differentiation of emotional versus neutral stimuli 90-300 ms following picture
      onset. Together with group differences in the lateral topography of valence
      effects, these results are discussed as evidence of deficient automatic
      processing of emotionally potent stimuli in schizophrenia.

PMID- 16965605
TI  - Differential integration efforts of mandatory and optional sentence constituents.
AB  - We investigated the online sensitivity of the semantic integration system to the
      different roles played by sentence constituents that are necessary (verbs and
      nouns) or optional (adjectives) for argument completion. We compared the effect
      of semantic incongruities introduced in both types of words on the N400 ERP
      component. Participants read sentences for meaning, half of which were rendered
      anomalous by an incongruent verb, noun, or an early/late adjective. Incongruent
      adjectives led to smaller N400 effects than did incongruent nouns and verbs, and
      the congruity effect for sentence-final adjectives was not significant. All
      incongruities are therefore not created equal: Incongruent optional sentence
      constituents create less of an integrative burden than incongruent mandatory
      sentence constituents, suggesting that online sentence integration processes are
      sensitive to the distinct roles played by different words in shaping sentence
      meaning.

PMID- 16965606
TI  - Electromyographic responses to static and dynamic avatar emotional facial
      expressions.
AB  - Facial muscular reactions to avatars' static (neutral, happy, angry) and dynamic
      (morphs developing from neutral to happy or angry) facial expressions, presented
      for 1 s each, were investigated in 48 participants. Dynamic expressions led to
      better recognition rates and higher intensity and realism ratings. Angry
      expressions were rated as more intense than happy expressions. EMG recordings
      indicated emotion-specific reactions to happy avatars as reflected in increased
      M. zygomaticus major and decreased M. corrugator supercilii tension, with
      stronger reactions to dynamic as compared to static expressions. Although rated
      as more intense, angry expressions elicited no significant M. corrugator
      supercilii activation. We conclude that facial reactions to angry and to happy
      facial expressions hold different functions in social interactions. Further
      research should vary dynamics in different ways and also include additional
      emotional expressions.

PMID- 16965607
TI  - Effects of acoustic distortion and semantic context on event-related potentials
      to spoken words.
AB  - This study examined the neurophysiological effects of acoustic degradation on
      auditory semantic processing. Event-related potentials were recorded to target
      words presented in a sentence context. Targets were semantically congruent or
      incongruent with the context, which was acoustically intact or low-pass filtered.
      In unaltered contexts, N400 amplitude was significantly greater for incongruent
      than congruent words. Filtering significantly reduced this effect, even though
      participants were highly accurate in interpreting the degraded stimuli, as shown
      by an anomaly detection task. This reduction in the N400 effect appeared to be
      driven by decreased N400 amplitudes over posterior electrode sites for
      incongruent targets. These results demonstrate that acoustic degradation
      influences the neural response to words in context by reducing the availability
      of semantic information in on-line sentence comprehension.

PMID- 16965608
TI  - Association between P3 event-related brain potential amplitude and adolescent
      problem behavior.
AB  - This study examined P3 event-related brain potential amplitude and the age of
      onset of adolescent problem behaviors associated with the development of
      externalizing psychopathology. Five hundred and one male and 627 female 17-year
      old twins reported whether and when they had initiated tobacco, alcohol, or
      illicit drug use, had police contact, or had sexual intercourse. P3 amplitude was
      recorded using a visual oddball task. Each of these behaviors was associated with
      reduced P3 amplitude. When these five behaviors were used to create a composite
      early problem behavior scale reflecting onset prior to age 15, higher scores were
      associated with smaller P3 amplitudes. P3 amplitude reduction has been associated
      with genetic risk for alcoholism and other externalizing disorders associated
      with disinhibited behavior. Our results suggest that reduced P3 may also be
      associated with early expression of behaviors that predict the development of
      these disorders.

PMID- 16965609
TI  - Heritability of P300 amplitude development from adolescence to adulthood.
AB  - Early adulthood is a period of late brain development corresponding to the age of
      onset for psychopathology associated with P300 amplitude reductions. Although
      amplitude from a single occasion is heritable, little is known about genetic
      influences on change during this period. This is the first study of P300 change
      to combine latent growth and twin models. P300 at Pz was measured up to three
      times at approximately ages 17, 20, and 23 in monozygotic and dizygotic male
      twins using a visual task. P300 decreased with age. Correlations indexing the
      stability of amplitude over time were high (median r=.72) and almost 90% of the
      stable variance (i.e., the model intercept) was attributable to genetic
      influences. The rate of decrease was heritable, and the genes influencing
      intercept may be the same ones influencing change. Finally, intercept was more
      heritable than amplitude at any single time point. Intercept may be a more useful
      aid in the search for genes associated with relevant psychopathology than single
      measures of P300. Over a broader age range growth indices may be useful
      "developmental" endophenotypes.

PMID- 16965610
TI  - Effects of pain-related anxiety on components of the pain event-related
      potential.
AB  - The aim of this study was to investigate whether components of pain event-related
      potentials (ERPs) are modulated by anxiety. Pain ERPs in response to electrical
      stimulation were collected from 14 healthy individuals in a neutral condition and
      a condition where pain-related anxiety was induced. The amplitude of the N140
      component of the ERP was found to be larger in the anxiety condition than the
      neutral condition. Arousal, as indicated by alpha power, did not differ between
      conditions. Differences in valence and focused attention to the painful stimuli
      may account for the increases in the N140 in the anxiety condition.

PMID- 16965611
TI  - A multi-process account of startle modulation during affective perception.
AB  - Modulation of the startle reflex by sensory, attentional, and emotional processes
      was explored by presenting acoustic startle probes at various delays following
      picture onset. Within 500 ms of onset, blinks were first greatly facilitated and
      then inhibited, indicating prepulse facilitation and prepulse inhibition that did
      not vary with affect. Attention allocation to the picture continued across the
      viewing interval and was most pronounced for emotional pictures, as determined by
      attenuation of the P3 component to the startle probe. Startle potentiation for
      unpleasant pictures occurred later in the viewing interval and was strongest for
      highly arousing pictures. Taken together, the startle reflex during picture
      viewing is modulated by sequential and sometimes concurrent processes of prepulse
      facilitation, prepulse inhibition, attentional inhibition, and affective
      modulation, with reflex magnitude reflecting the net effect of multiple
      processes.

PMID- 16965612
TI  - Effects of perceptual load on startle reflex modification at a long lead
      interval.
AB  - Inhibition of the startle eyeblink response at long lead intervals has been
      hypothesized to occur when attention is directed away from the modality of the
      startle stimulus, particularly if attention is directed to a stimulus of high
      perceptual load. In a test of this hypothesis, participants performed a delayed
      matching-to-sample task. On each trial a pattern of dots (the sample) was
      followed by a second pattern of dots (the target). The task was to say whether
      the sample and target patterns matched. Perceptual load was manipulated by
      varying the number of dots in the sample. Auditory startle stimuli were presented
      1200 ms after onset of the samples. A linear increase in startle magnitude was
      found as the number of dots increased. The results are not consistent with the
      hypothesis that startle inhibition occurs when the lead and startle stimuli are
      in different modalities under conditions of high perceptual load.

PMID- 16965613
TI  - Attentional blink and prepulse inhibition of startle are positively correlated.
AB  - Although a link between the attentional blink and prepulse startle inhibition has
      been considered, no evidence of this relationship has been reported. We delivered
      acoustic startle probes during rapid serial visual presentations in which the
      relative positions of two targets (targets 1 and 2) was varied within a stream of
      distractors. Startle probes were presented at 100 ms lead intervals relative to
      onset of a target or distractor. We found positive correlations between visual
      prepulse inhibition and attentional blink effects across participants. As the
      magnitude of prepulse inhibition with target and distractor lead stimuli
      increased, deficits in identifying target 2 during the attentional blink
      increased, suggesting similar processes underlying these phenomena. Whereas
      prepulse inhibition may reveal the strength of inhibition to protect stimulus
      processing, attentional blink may index the rate of recovery from similar
      inhibitory processes.

PMID- 16965614
TI  - Infrared reflectance as an alternative to EMG for measuring prepulse inhibition
      of startle eyeblink.
AB  - The "gold standard" measure of the human startle eyeblink response is the ocular
      electromyogram (EMG). However, EMG measurement is not always feasible, as with
      special populations or during functional neuroimaging. We evaluated an
      alternative, nonelectrical, noncontact measure that uses infrared (IR) light
      reflected from the eye. By simultaneously recording IR and EMG during an acoustic
      prepulse inhibition of startle paradigm, we were able to directly compare the two
      measures and evaluate the relative reliability and validity of the IR measure as
      an index of startle response modulation. Although fewer responses were detected
      using IR than EMG, both measures were equally sensitive to prepulse modulation of
      response amplitude, latency, and probability. We conclude that when the goal is
      simply to assess the effects of a prepulse on the startle response, IR
      reflectance is an adequate alternative to EMG.

PMID- 16965615
TI  - Trace metal concentrations in Posidonia oceanica of North Corsica (northwestern
      Mediterranean Sea): use as a biological monitor?
AB  - BACKGROUND: Within semi-closed areas like the Mediterranean Sea, anthropic wastes
      tend to concentrate in the environment. Metals, in particular, are known to
      persist in the environment and can affect human health due to accumulation in the
      food chain. The seagrass Posidonia oceanica, widely found in Mediterranean
      coastal waters, has been chosen as a "sentinel" to quantify the distribution of
      such pollutants within the marine environment. Using a technique similar to
      dendrochronology in trees, it can act as an indicator of pollutant levels over a
      timeframe of several months to years. In the present study, we measured and
      compared the levels of eight trace metals (Cr, Ni, Cu, Zn, As, Se, Cd, and Pb) in
      sheaths dated by lepidochronology and in leaves of shoots sampled from P.
      oceanica meadows collected from six offshore sites in northern Corsica between
      1988 and 2004; in the aim to determine 1) the spatial and 2) temporal variations
      of these metals in these areas and 3) to compared these two types of tissues.
      RESULTS: We found low trace metal concentrations with no increase over the last
      decade, confirming the potential use of Corsican seagrass beds as reference sites
      for the Mediterranean Sea. Temporal trends of trace metal concentrations in
      sheaths were not significant for Cr, Ni, Cu, As or Se, but Zn, Cd, and Pb levels
      decreased, probably due to the reduced anthropic use of these metals. Similar
      temporal trends between Cu levels in leaves (living tissue) and in sheaths (dead
      tissue) demonstrated that lepidochronology linked with Cu monitoring is effective
      for surveying the temporal variability of this metal. CONCLUSION: Leaves of P.
      oceanica can give an indication of the metal concentration in the environment
      over a short time period (months) with good accuracy. On the contrary, sheaths,
      which gave an indication of changes over long time periods (decades), seem to be
      less sensitive to variations in the metal concentration in the environment.
      Changes in human consumption of metals (e.g., the reduction of Pb in fuel) are
      clearly reflected in both organs. These results confirm that P. oceanica is a
      good bioindicator of metals and a good biomonitor species for assessing Cu in the
      environment.

PMID- 16965616
TI  - Radiation induced angiosarcoma a sequela of radiotherapy for breast cancer
      following conservative surgery.
AB  - Radiation induced angiosarcomas (RIA) can affect breast cancer patients who had
      radiotherapy following conservative breast surgery. They are very rare tumors and
      often their diagnosis is delayed due to their benign appearance and difficulty in
      differentiation from radiation induced skin changes. Therefore it is very
      important that clinicians are aware of their existence. We report here a case of
      RIA followed by discussion and review of literature.

PMID- 16965617
TI  - Hemicraniectomy after middle cerebral artery infarction with life-threatening
      Edema trial (HAMLET). Protocol for a randomised controlled trial of decompressive
      surgery in space-occupying hemispheric infarction.
AB  - BACKGROUND: Patients with a hemispheric infarct and massive space-occupying brain
      oedema have a poor prognosis. Despite maximal conservative treatment, the case
      fatality rate may be as high as 80%, and most survivors are left severely
      disabled. Non-randomised studies suggest that decompressive surgery reduces
      mortality substantially and improves functional outcome of survivors. This study
      is designed to compare the efficacy of decompressive surgery to improve
      functional outcome with that of conservative treatment in patients with space
      occupying supratentorial infarction METHODS: The study design is that of a multi
      centre, randomised clinical trial, which will include 112 patients aged between
      18 and 60 years with a large hemispheric infarct with space-occupying oedema that
      leads to a decrease in consciousness. Patients will be randomised to receive
      either decompressive surgery in combination with medical treatment or best
      medical treatment alone. Randomisation will be stratified for the intended mode
      of conservative treatment (intensive care or stroke unit care). The primary
      outcome measure will be functional outcome, as determined by the score on the
      modified Rankin Scale, at one year.

PMID- 16965618
TI  - Myocardial injury in infants ventilated on the paediatric intensive care unit: a
      case control study.
AB  - INTRODUCTION: Cardiac troponin T (cTnT) has been used to assess prevalence of
      myocardial injury in critically ill children. The majority of studies
      investigated patients undergoing cardiac surgery. Myocardial injury has been
      associated with increased mortality. Our objectives were to investigate whether
      cTnT levels are elevated in infants without congenital heart disease admitted to
      the paediatric intensive care unit (PICU) and whether levels are associated with
      increased disease severity. METHODS: We measured cTnT in consecutive infants (<12
      months old) without congenital heart disease admitted to the PICU and healthy
      infants. The Paediatric Index of Mortality (PIM) score was determined in patients
      on the PICU. RESULTS: We recruited 107 infants: 47 infants admitted to the PICU
      and 60 healthy controls. Controls were, with a median (interquartile range (IQR))
      age of 20 (12 to 34) weeks, significantly older than cases, with a median age of
      6.5 (0.3 to 20.6) weeks. CTnT levels were, with a median (IQR) of 18 (10 to 60)
      pg/ml, significantly higher in admissions to the PICU than in controls, with a
      median level of 10 (10 to 10) pg/ml (95th centile of 20 pg/ml) (p < 0.001). There
      was a significant positive correlation (r = 0.41, p = 0.004) between PIM score
      and cTnT levels. Admissions under one month old had higher cTnT levels than older
      patients (p = 0.013) but the PIM score was not significantly different between
      them. When corrected for age and weight the correlation of PIM and cTnT was no
      longer significant. CONCLUSION: Infants on the PICU in the neonatal period have
      higher cTnT levels compared to older infants despite not having more severe
      disease.

PMID- 16965619
TI  - Natural distribution of environmental radon daughters in the different brain
      areas of an Alzheimer disease victim.
AB  - BACKGROUND: Radon is a ubiquitous noble gas in the environment and a primary
      source of harmful radiation exposure for humans; it decays in a cascade of
      daughters (RAD) by releasing the cell damaging high energy alpha particles.
      RESULTS: We studied natural distribution of RAD 210Po and 210Bi in the different
      parts of the postmortem brain of 86-year-old woman who had suffered from
      Alzheimer's disease (AD). A distinct brain map emerged, since RAD distribution
      was different among the analyzed brain areas. The highest RAD irradiation (mSv x
      year(-1)) occurred in the decreasing order of magnitude: amygdala (Amy) >>
      hippocampus (Hip) > temporal lobe (Tem) approximately = frontal lobe (Fro) >
      occipital lobe (Occ) approximately = parietal lobe (Par) > substantia nigra (SN)
      >> locus ceruleus (LC) approximately = nucleus basalis (NB); generally more RAD
      accumulated in the proteins than lipids of gray and white (gray > white) brain
      matter. Amy and Hip are particularly vulnerable brain structure targets to
      significant RAD internal radiation damage in AD (5.98 and 1.82 mSv x year(-1),
      respectively). Next, naturally occurring RAD radiation for Tem and Fro, then Occ
      and Par, and SN was an order of magnitude higher than that in LC and NB; the
      later was within RAD we observed previously in the healthy control brains.
      CONCLUSION: Naturally occurring environmental RAD exposure may dramatically
      enhance AD deterioration by selectively targeting brain areas of emotions (Amy)
      and memory (Hip).

PMID- 16965620
TI  - Tissue- and hormone-dependent progesterone receptor distribution in the rat
      uterus.
AB  - BACKGROUND: Estradiol (E2) and progesterone (P) are well known regulators of
      progesterone receptor (PR) expression in the rat uterus. However, it is not known
      which receptor subtypes are involved. Little knowledge exist about possible
      differences in PR regulation through ERalpha or ERbeta, and whether the PR
      subtypes are differently regulated depending on ER type bound. Thus, in the
      present study PR immunostaining has been examined in uteri of ovariectomized
      (ovx) rats after different treatments of estrogen and P, in comparison with that
      in immature, cycling, and pregnant animals. METHODS: The uteri were collected
      from 1) ovx rats treated with E2 and/or P; 2) immature rats, intact cycling rats
      and animals pregnant day 8 and 18; 3) ovx rats treated with E2 or an estrogen
      receptor (ER)alpha agonist or an ERbeta agonist. Two antibodies were used, one
      detecting PRA+B and another one specific for PRB. Real-time PCR was used to
      determine mRNA levels for PRAB and PRB in experiment 3. RESULTS: In stroma and
      myometrium faint staining was detected in ovx controls (OvxC), whereas E2
      treatment resulted in strong staining. In contrast to this, in luminal epithelium
      (LE) the staining was strong in the OvxC group, whereas E2 treatment during the
      last 24 hrs before sacrifice caused a decrease. Similar to OvxC the LE of the
      immature animals was strongly stained. In the pregnant rats LE was negative, well
      in agreement with the results seen after E2 treatment. In the pregnant animals
      the stroma and decidua was strongly stained for PRAB, but only faint for PRB,
      indicating that PRA is the most expressed isoform in this state. The increase in
      stromal and myometrial immunostaining after E2 treatment was also found after
      treatment with the ERalpha agonist PPT. The ERbeta agonist DPN caused a decrease
      of the PR mRNA levels, which was also found for PRAB and PRB immunostaining in
      the GE. CONCLUSION: Stromal and myometrial PRAB levels are increased via ERalpha,
      as shown by treatment with E2 and the ERalpha agonist PPT, while the levels in LE
      are decreased. The uterine stroma of pregnant rats strongly expressed PRAB, but
      very little PRB, which is different to E2 treated ovx animals where both PRAB and
      PRB are strongly expressed. The ERbeta agonist DPN decreased the mRNA levels of
      PRAB and PRB, as well as the PRAB protein level in GE. These results suggest that
      ERbeta signals mainly down-regulate PR levels in the epithelial cells. ERalpha,
      on the other hand, up-regulates PR levels in the stroma and myometrium while it
      decreased them in LE. Thus, the effects from E2 and PPT on the mRNA levels, as
      determined by PCR, could be annihilated since they are increased and decreased
      depending on cell type. The distribution and amount of PR isoforms strongly
      depend on the hormonal milieu and cell type within the rat uterus.

PMID- 16965621
TI  - Needs for care among patients with schizophrenia in six European countries: a one
      year follow-up study.
AB  - BACKGROUND: This article compares needs for care among patients with
      schizophrenia across six European countries and examines how this relates to the
      diversity of psychiatric systems in Europe. METHODS: A one-year prospective
      cohort study was set up. Inclusion criteria for patients were: a clinical
      lifetime diagnosis of schizophrenia according to ICD-10 (F20) diagnostic criteria
      for research, age between 18 and 65 years and at least one contact with mental
      health services in 1993. The patients were assessed for their clinical diagnosis
      and symptoms using the SCAN interview (Schedules for Clinical Assessment in
      Neuropsychiatry) and the interventions proposed to them were recorded through the
      systematic use of the NFCAS (Needs For Care Assessment Schedule). RESULTS: 438
      patients were included and 391 were followed up. The mean age was 38 years, the
      mean age at onset was 22 years, and 59% were out-patients, 24% in day care and
      15% hospitalized. The populations in the different centres were significantly
      different for almost all the variables: sociodemographic, clinical and social,
      and the problems identified remained relatively stable over the year. Comparisons
      highlighted cultural differences concerning the interventions that were proposed.
      Centres in Italy, Spain and Portugal proposed many interventions even though they
      were relatively deprived in terms of resources, and the tendency seems to be the
      reverse for the Northern European countries. On average, one in four patients
      suffered from needs that were not adequately met by the mental health service in
      their region. These needs (on average 6 per patient) varied from psychotic
      symptoms to managing their own affairs. The number of interventions was not
      correlated to the need status. The availability of community-based treatment,
      rehabilitation and residential care seems to predict smaller proportions of
      patients with unmet needs. CONCLUSION: There appeared to be a systematic
      relationship between the availability of community-based mental health care and
      the need status of schizophrenic patients: the fewer out-patient and
      rehabilitation services available, the more unmet needs there were.

PMID- 16965622
TI  - Immunohistochemical localization patterns for vimentin and other intermediate
      filaments in calcified ovarian fibrothecoma.
AB  - PROBLEM: To describe immunohistochemical features encountered in ovarian
      fibrothecoma with correlation to clinical presentation and surgical management.
      METHOD OF STUDY: A female age 75 presented for evaluation of melena. The patient
      reported total abdominal hysterectomy and removal of both ovaries 40 years
      earlier. RESULTS: CA-125 was normal and there was no evidence of hyperestrogen
      effect. Pelvic CT revealed a partially calcified 7 cm pelvic mass without
      adenopathy or ascites; ultrasound was confirmatory. Endoscopy identified three
      benign intestinal tubular adenomas. Following laparoscopic excision of the pelvic
      tumor immunohistochemical analysis of the mass showed negative staining for
      keratin, S100 protein, inhibin, calretinin, melan A, smooth muscle actin, CD34,
      CD117, and desmin. The tissue was positive for vimentin, however. CONCLUSION:
      Ovarian fibrothecomas represent an ovarian stromal neoplasm developing in a wide
      spectrum of clinical settings. Particularly if oophorectomy is stated to have
      been performed remote from the time of index presentation, the status of the
      ovaries must be considered whenever pelvic pathology is encountered. We describe
      a calcified ovarian fibrothecoma identified during gastroenterology investigation
      and confirmed immunohistochemically via high amplitude vimentin signal.

PMID- 16965623
TI  - An unusual foreign body migrating through time and tissues.
AB  - BACKGROUND: Beside infections, foreign body incidences are amongst the most
      frequently encountered pathologies in pediatric otolaryngology. While inhaled
      foreign bodies represent an acute emergency, symptoms of ingested foreign bodies
      sometimes appear with some delay. Typically fishbones tend to go unnoticed in a
      first examination and become symptomatic by fever, odynodysphagia and
      torticollis. Exceptionally, foreign bodies migrate and become manifest with a
      considerable delay. CASE REPORT: We present a case of a young girl who presented
      with an unusual foreign body which migrated through the cervical tissues causing
      repeated cervical tumescence's before being diagnosed. CONCLUSION: Repeated
      cervical abscesses or tumescence's in children or young patients should alert the
      treating physician to seek for an underlying pathology such as unnoticed foreign
      bodies or malformations (e.g. cysts). Further the scarce literature on these
      migrating foreign bodies is discussed.

PMID- 16965624
TI  - Novel low-kVp beamlet system for choroidal melanoma.
AB  - BACKGROUND: Treatment of choroidal melanoma with radiation often involves
      placement of customized brachytherapy eye-plaques. However, the dosimetric
      properties inherent in source-based radiotherapy preclude facile dose
      optimization to critical ocular structures. Consequently, we have constructed a
      novel system for utilizing small beam low-energy radiation delivery, the Beamlet
      Low-kVp X-ray, or "BLOKX" system. This technique relies on an isocentric
      rotational approach to deliver dose to target volumes within the eye, while
      potentially sparing normal structures. METHODS: Monte Carlo N-Particle (MCNP)
      transport code version 5.0(14) was used to simulate photon interaction with
      normal and tumor tissues within modeled right eye phantoms. Five modeled dome
      shaped tumors with a diameter and apical height of 8 mm and 6 mm, respectively,
      were simulated distinct positions with respect to the macula iteratively. A
      single fixed 9 x 9 mm2 beamlet, and a comparison COMS protocol plaque containing
      eight I-125 seeds (apparent activity of 8 mCi) placed on the scleral surface of
      the eye adjacent to the tumor, were utilized to determine dosimetric parameters
      at tumor and adjacent tissues. After MCNP simulation, comparison of dose
      distribution at each of the 5 tumor positions for each modality (BLOKX vs. eye
      plaque) was performed. RESULTS: Tumor-base doses ranged from 87.1-102.8 Gy for
      the BLOKX procedure, and from 335.3-338.6 Gy for the eye-plaque procedure. A
      reduction of dose of at least 69% to tumor base was noted when using the BLOKX.
      The BLOKX technique showed a significant reduction of dose, 89.8%, to the macula
      compared to the episcleral plaque. A minimum 71.0 % decrease in dose to the optic
      nerve occurred when the BLOKX was used. CONCLUSION: The BLOKX technique allows
      more favorable dose distribution in comparison to standard COMS brachytherapy, as
      simulated using a Monte Carlo iterative mathematical modeling. Future series to
      determine clinical utility of such an approach are warranted.

PMID- 16965625
TI  - Clinical manifestations and outcome in Staphylococcus aureus endocarditis among
      injection drug users and nonaddicts: a prospective study of 74 patients.
AB  - BACKGROUND: Endocarditis is a common complication in Staphylococcus aureus
      bacteremia (SAB). We compared risk factors, clinical manifestations, and outcome
      in a large, prospective cohort of patients with S. aureus endocarditis in
      injection drug users (IDUs) and in nonaddicts. METHODS: Four hundred and thirty
      consecutive adult patients with SAB were prospectively followed up for 3 months.
      Definite or possible endocarditis by modified Duke criteria was found in 74
      patients: 20 patients were IDUs and 54 nonaddicts. RESULTS: Endocarditis was more
      common in SAB among drug abusers (46%) than in nonaddicts (14%) (odds ratio [OR],
      5.12; 95% confidence interval [CI], 2.65-9.91; P < 0.001). IDUs were
      significantly younger (27 +/- 15 vs 65 +/- 15 years, P < 0.001), had less
      ultimately or rapidly fatal underlying diseases (0% vs 37%, P < 0.001) or
      predisposing heart diseases (20% vs 50%, P = 0.03), and their SAB was more often
      community-acquired (95% vs 39%, P < 0.001). Right-sided endocarditis was observed
      in 60% of IDUs whereas 93% of nonaddicts had left-sided involvement (P < 0.001).
      An extracardiac deep infection was found in 85% of IDUs and in 89% of nonaddicts
      (P = 0.70). Arterial thromboembolic events and severe sepsis were also equally
      common in both groups. There was no difference in mortality between the groups at
      7 days, but at 3 months it was lower among IDUs (10%) compared with nonaddicts
      (39%) (OR, 5.73; 95% CI, 1.20-27.25; P = 0.02). CONCLUSION: S. aureus
      endocarditis in IDUs was associated with as high complication rates including
      extracardiac deep infections, thromboembolic events, or severe sepsis as in
      nonaddicts. Injection drug abuse in accordance with younger age and lack of
      underlying diseases were associated with lower mortality, but after adjusting by
      age and underlying diseases injection drug abuse was not significantly associated
      with mortality.

PMID- 16965626
TI  - Inhibition of secreted phospholipase A2 by neuron survival and anti-inflammatory
      peptide CHEC-9.
AB  - BACKGROUND: The nonapeptide CHEC-9 (CHEASAAQC), a putative inhibitor of secreted
      phospholipase A2 (sPLA2), has been shown previously to inhibit neuron death and
      aspects of the inflammatory response following systemic treatment of rats with
      cerebral cortex lesions. In this study, the properties of CHEC-9 inhibition of
      sPLA2 enzymes were investigated, using a venom-derived sPLA2 group I and the
      plasma of rats and humans as the sources of enzyme activity. The results
      highlight the advantages of inhibitors with uncompetitive properties for
      inflammatory disorders including those resulting in degeneration of neurons.
      METHODS: Samples of enzyme and plasma were reacted with 1-Palmitoyl-2
      Pyrenedecanoyl Phosphatidylcholine, a sPLA2 substrate that forms phospholipid
      vesicles in aqueous solutions. Some of the plasma samples were collected from
      restrained peptide-treated rats in order to confirm the validity of the in vitro
      assays for extrapolation to in vivo effects of the peptide. The enzyme reactions
      were analyzed in terms of well-studied relationships between the degree of
      inhibition and the concentrations of different reactants. We also examined
      interactions between different components of the reaction mixture on native
      polyacrylamide gels. RESULTS: In all cases, the peptide showed the properties of
      an uncompetitive (or anti-competitive) enzyme inhibitor with Ki values less than
      100 nanomolar. The electrophoresis experiments suggested CHEC-9 modifies the
      binding properties of the enzyme only in the presence of substrate, consistent
      with its classification as an uncompetitive inhibitor. Both the in vitro
      observations and the analysis of plasma samples from restrained rats injected
      with peptide suggest the efficacy of the peptide increases under conditions of
      high enzyme activity. CONCLUSION: Modeling studies by others have shown that
      uncompetitive inhibitors may be optimal for enzyme inhibition therapy because,
      unlike competitive inhibitors, they are not rendered ineffective by the
      accumulation of unmodified substrate. Such conditions likely apply to several
      instances of neuroinflammation where there are cascading increases in sPLA2s and
      their substrates, both systemically and in the CNS. Thus, the present results may
      explain the efficacy of CHEC-9 in vivo.

PMID- 16965627
TI  - Secreted phospholipase A2 activity in experimental autoimmune encephalomyelitis
      and multiple sclerosis.
AB  - BACKGROUND: There is increased interest in the contribution of the innate immune
      system to multiple sclerosis (MS), including the activity of acute inflammatory
      mediators. The purpose of this study was to test the involvement of systemic
      secreted phospholipase A2 (sPLA2) enzymes in experimental autoimmune
      encephalomyelitis (EAE), an MS model, and to determine if enzyme activity is
      elevated in MS patients. METHODS: A non-invasive urinary assay was developed in
      order to monitor enzymatically active sPLA2 levels in Dark Agouti rats after
      induction of EAE. Some Rats were treated with nonapeptide CHEC-9, an
      uncompetitive sPLA2 enzyme inhibitor, during the initial rise in urinary enzyme
      levels. Body weight and clinical EAE score were measured for 18 days post
      immunization (PI), after which the rats were sacrificed for H&E and myelin
      staining, and for ED-1 immunocytochemistry, the latter to quantify macrophages
      and activated microglia. The urinary sPLA2 assay was also applied to un-timed
      samples collected from a cross section of 44 MS patients and 14 healthy controls.
      RESULTS: Mean levels of enzymatically active sPLA2 in the urine increased
      following immunization and peaked between days 8-10 PI which was just prior to
      the onset of EAE symptoms. At this time, a transient attenuation of activity was
      detected in the urine of CHEC-9 treated rats consistent with the activity
      dependent properties of the inhibitor. The peptide also reduced or abolished EAE
      symptoms compared to vehicle-injected controls. Histopathological changes in the
      spinal cords of the EAE rats correlated generally with clinical score including a
      significant reduction in ED-1+ cells after peptide treatment. Multiple Sclerosis
      patients also showed elevations in sPLA2 enzyme activity. Mean levels of sPLA2
      were increased 6-fold in the urine of patients with active disease and 4-fold for
      patients in remission, regardless of immunomodulating therapy. CONCLUSION: The
      results suggest that sPLA2 enzymes, traditionally thought to be part the acute
      phase inflammatory response, are therapeutic targets for MS.

PMID- 16965628
TI  - Does a "Level I Evidence" rating imply high quality of reporting in orthopaedic
      randomised controlled trials?
AB  - BACKGROUND: The Levels of Evidence Rating System is widely believed to categorize
      studies by quality, with Level I studies representing the highest quality
      evidence. We aimed to determine the reporting quality of Randomised Controlled
      Trials (RCTs) published in the most frequently cited general orthopaedic
      journals. METHODS: Two assessors identified orthopaedic journals that reported a
      level of evidence rating in their abstracts from January 2003 to December 2004 by
      searching the instructions for authors of the highest impact general orthopaedic
      journals. Based upon a priori eligibility criteria, two assessors hand searched
      all issues of the eligible journal from 2003-2004 for RCTs. The assessors
      extracted the demographic information and the evidence rating from each included
      RCT and scored the quality of reporting using the reporting quality assessment
      tool, which was developed by the Cochrane Bone, Joint and Muscle Trauma Group.
      Scores were conducted in duplicate, and we reached a consensus for any
      disagreements. We examined the correlation between the level of evidence rating
      and the Cochrane reporting quality score. RESULTS: We found that only the Journal
      of Bone and Joint Surgery - American Volume (JBJS-A) used a level of evidence
      rating from 2003 to 2004. We identified 938 publications in the JBJS-A from
      January 2003 to December 2004. Of these publications, 32 (3.4%) were RCTs that
      fit the inclusion criteria. The 32 RCTs included a total of 3543 patients, with
      sample sizes ranging from 17 to 514 patients. Despite being labelled as the
      highest level of evidence (Level 1 and Level II evidence), these studies had low
      Cochrane reporting quality scores among individual methodological safeguards. The
      Cochrane reporting quality scores did not differ significantly between Level I
      and Level II studies. Correlations varied from 0.0 to 0.2 across the 12 items of
      the Cochrane reporting quality assessment tool (p > 0.05). Among items closely
      corresponding to the Levels of Evidence Rating System criteria assessors achieved
      substantial agreement (ICC = 0.80, 95% CI:0.60 to 0.90). CONCLUSION: Our findings
      suggest that readers should not assume that 1) studies labelled as Level I have
      high reporting quality and 2) Level I studies have better reporting quality than
      Level II studies. One should address methodological safeguards individually.

PMID- 16965629
TI  - Efficacy and clinical effectiveness of influenza vaccines in HIV-infected
      individuals: a meta-analysis.
AB  - BACKGROUND: Though influenza vaccines are the cornerstone of medical
      interventions aimed at protecting individuals against epidemic influenza, their
      effectiveness in HIV infected individuals is not certain. With the recent
      detection of influenza strains in countries with high HIV prevalence rates, we
      aimed at evaluating the current evidence on the efficacy and clinical
      effectiveness of influenza vaccines in HIV-infected individuals. METHODS: We used
      electronic databases to identify studies assessing efficacy or effectiveness of
      influenza vaccines in HIV patients. We included studies that compared the
      incidence of culture- or serologically-confirmed influenza or clinical influenza
      like illness in vaccinated to unvaccinated HIV infected individuals.
      Characteristics of study participants were independently abstracted and the risk
      difference (RD), the number needed to vaccinate to prevent one case of influenza
      (NNV) and the vaccine effectiveness (VE) computed. RESULTS: We identified six
      studies that assessed the incidence of influenza in vaccinated HIV-infected
      subjects. Four of these studies compared the incidence in vaccinated versus
      unvaccinated subjects. These involved a total of 646 HIV-infected subjects. In
      all the 4 studies, the incidence of influenza was lower in the vaccinated
      compared to unvaccinated subjects with RD ranging from -0.48 (95% CI: -0.63, 
      0.34) to -0.15 (95% CI: -0.25, 0.05); between 3 and 7 people would need to be
      vaccinated to prevent one case of influenza. Vaccine effectiveness ranged from
      27% to 78%. A random effects model was used to obtain a summary RD of -0.27
      (95%CI: -0.42, -0.11). There was no evidence of publication bias. CONCLUSION:
      Current evidence, though limited, suggests that influenza vaccines are moderately
      effective in reducing the incidence of influenza in HIV-infected individuals.
      With the threat of a global influenza pandemic, there is an urgent need to
      evaluate the effectiveness of influenza vaccines in trials with a larger number
      of representative HIV-infected persons.

PMID- 16965630
TI  - Oxygen cost of dynamic or isometric exercise relative to recruited muscle mass.
AB  - BACKGROUND: Oxygen cost of different muscle actions may be influenced by
      different recruitment and rate coding strategies. The purpose of this study was
      to account for these strategies by comparing the oxygen cost of dynamic and
      isometric muscle actions relative to the muscle mass recruited via surface
      electrical stimulation of the knee extensors. METHODS: Comparisons of whole body
      pulmonary delta VO2 were made in seven young healthy adults (1 female) during 3
      minutes of dynamic or isometric knee extensions, both induced by surface
      electrical stimulation. Recruited mass was quantified in T2 weighted spin echo
      magnetic resonance images. RESULTS: The delta VO2 for dynamic muscle actions, 242
      +/- 128 ml x min(-1) (mean +/- SD) was greater (p = 0.003) than that for
      isometric actions, 143 +/- 99 ml x min(-1). Recruited muscle mass was also
      greater (p = 0.004) for dynamic exercise, 0.716 +/- 282 versus 0.483 +/- 0.139
      kg. The rate of oxygen consumption per unit of recruited muscle (VO2(RM)) was
      similar in dynamic and isometric exercise (346 +/- 162 versus 307 +/- 198 ml x
      kg(-1) x min(-1); p = 0.352), but the VO2(RM) calculated relative to initial knee
      extensor torque was significantly greater during dynamic exercise 5.1 +/- 1.5
      versus 3.6 +/- 1.6 ml x kg(-1) x Nm(-1) x min(-1) (p = 0.019). CONCLUSION: These
      results are consistent with the view that oxygen cost of dynamic and isometric
      actions is determined by different circumstances of mechanical interaction
      between actin and myosin in the sarcomere, and that muscle recruitment has only a
      minor role.

PMID- 16965631
TI  - Global bioethics -- myth or reality?
AB  - BACKGROUND: There has been debate on whether a global or unified field of
      bioethics exists. If bioethics is a unified global field, or at the very least a
      closely shared way of thinking, then we should expect bioethicists to behave the
      same way in their academic activities anywhere in the world. This paper
      investigates whether there is a 'global bioethics' in the sense of a unified
      academic community. METHODS: To address this question, we study the web-linking
      patterns of bioethics institutions, the citation patterns of bioethics papers and
      the buying patterns of bioethics books. RESULTS: All three analyses indicate that
      there are geographical and institutional differences in the academic behavior of
      bioethicists and bioethics institutions. CONCLUSION: These exploratory studies
      support the position that there is no unified global field of bioethics. This is
      a problem if the only reason is parochialism. But these regional differences are
      probably of less concern if one notices that bioethics comes in many not always
      mutually understandable dialects.

PMID- 16965633
TI  - Wealth and sexual behaviour among men in Cameroon.
AB  - BACKGROUND: The 2004 Demographic and Health Survey (DHS) in Cameroon revealed a
      higher prevalence of HIV in richest and most educated people than their poorest
      and least educated compatriots. It is not certain whether the higher prevalence
      results partly or wholly from wealthier people adopting more unsafe sexual
      behaviours, surviving longer due to greater access to treatment and care, or
      being exposed to unsafe injections or other HIV risk factors. As unsafe sex is
      currently believed to be the main driver of the HIV epidemic in sub-Saharan
      Africa, we designed this study to examine the association between wealth and
      sexual behaviour in Cameroon. METHODS: We analysed data from 4409 sexually active
      men aged 15-59 years who participated in the Cameroon DHS using logistic
      regression models, and have reported odds ratios (OR) with confidence intervals
      (CI). RESULTS: When we controlled for the potential confounding effects of
      marital status, place of residence, religion and age, men in the richest third of
      the population were less likely to have used a condom in the last sex with a non
      spousal non-cohabiting partner (OR 0.43, 95% CI 0.32-0.56) and more likely to
      have had at least two concurrent sex partners in the last 12 months (OR 1.38, 95%
      CI 1.12-1.19) and more than five lifetime sex partners (OR 1.97, 95% CI 1.60
      2.43). However, there was no difference between the richest and poorest men in
      the purchase of sexual services. Regarding education, men with secondary or
      higher education were less likely to have used a condom in the last sex with a
      non-spousal non-cohabiting partner (OR 0.24, 95% CI 0.16-0.38) and more likely to
      have started sexual activity at age 17 years or less (OR 2.73, 95% CI 2.10-3.56)
      and had more than five lifetime sexual partners (OR 2.59, 95% CI 2.02-3.31).
      There was no significant association between education and multiple concurrent
      sexual partnerships in the last 12 months or purchase of sexual services.
      CONCLUSION: Wealthy men in Cameroon are more likely to start sexual activity
      early and have both multiple concurrent and lifetime sex partners, and are less
      likely to (consistently) use a condom in sex with a non-spousal non-cohabiting
      partner. These unsafe sexual behaviours may explain the higher HIV prevalence
      among wealthier men in the country. While these findings do not suggest a
      redirection of HIV prevention efforts from the poor to the wealthy, they do call
      for efforts to ensure that HIV prevention messages get across all strata of
      society.

PMID- 16965632
TI  - Induction of cell cycle changes and modulation of apoptogenic/anti-apoptotic and
      extracellular signaling regulatory protein expression by water extracts of I'm
      Yunity (PSP).
AB  - BACKGROUND: I'm-Yunity (PSP) is a mushroom extract derived from deep-layer
      cultivated mycelia of the patented Cov-1 strain of Coriolus versicolor (CV),
      which contains as its main bioactive ingredient a family of polysaccharo-peptide
      with heterogeneous charge properties and molecular sizes. I'm-Yunity (PSP) is
      used as a dietary supplement by cancer patients and by individuals diagnosed with
      various chronic diseases. Laboratory studies have shown that I'm-Yunity (PSP)
      enhances immune functions and also modulates cellular responses to external
      challenges. Recently, I'm-Yunity (PSP) was also reported to exert potent anti
      tumorigenic effects, evident by suppression of cell proliferation and induction
      of apoptosis in malignant cells. We investigate the mechanisms by which I'm
      Yunity (PSP) elicits these effects. METHODS: Human leukemia HL-60 and U-937 cells
      were incubated with increasing doses of aqueous extracts of I'm-Yunity (PSP).
      Control and treated cells were harvested at various times and analyzed for
      changes in: (1) cell proliferation and viability, (2) cell cycle phase
      transition, (3) induction of apoptosis, (4) expression of cell cycle,
      apoptogenic/anti-apoptotic, and extracellular regulatory proteins. RESULTS:
      Aqueous extracts of I'm-Yunity (PSP) inhibited cell proliferation and induced
      apoptosis in HL-60 and U-937 cells, accompanied by a cell type-dependent
      disruption of the G1/S and G2/M phases of cell cycle progression. A more
      pronounced growth suppression was observed in treated HL-60 cells, which was
      correlated with time- and dose-dependent down regulation of the retinoblastoma
      protein Rb, diminution in the expression of anti-apoptotic proteins bcl-2 and
      survivin, increase in apoptogenic proteins bax and cytochrome c, and cleavage of
      poly(ADP-ribose) polymerase (PARP) from its native 112-kDa form to the 89-kDa
      truncated product. Moreover, I'm-Yunity (PSP)-treated HL-60 cells also showed a
      substantial decrease in p65 and to a lesser degree p50 forms of transcription
      factor NF-kappaB, which was accompanied by a reduction in the expression of
      cyclooxygenase 2 (COX2). I'm-Yunity (PSP) also elicited an increase in STAT1
      (signal transducer and activator of transcription) and correspondingly, decrease
      in the expression of activated form of ERK (extracellular signal-regulated
      kinase). CONCLUSION: Aqueous extracts of I'm-Yunity (PSP) induces cell cycle
      arrest and alterations in the expression of apoptogenic/anti-apoptotic and
      extracellular signaling regulatory proteins in human leukemia cells, the net
      result being suppression of proliferation and increase in apoptosis. These
      findings may contribute to the reported clinical and overall health effects of
      I'm-Yunity (PSP).

PMID- 16965634
TI  - Long-term changes of serum chemokine levels in vaccinated military personnel.
AB  - BACKGROUND: Members of the United States Armed Forces receive a series of
      vaccinations during their course of service. To investigate the influence of
      multiple vaccinations on innate immunity, we measured concentrations of a panel
      of immunomodulatory and pro-inflammatory cytokines in serum samples from a group
      of such individuals. RESULTS: Significantly increased levels of macrophage
      inflammatory protein 1alpha (MIP-1alpha), MIP-1beta and interleukin 8 (IL-8) were
      detected. Since these cytokines are known to have anti-human immunodeficiency
      virus (HIV) activity, we tested the effect of serum from these individuals on HIV
      1 infectivity and susceptibility of their peripheral blood mononuclear cells
      (PBMCs) to HIV-1 infection in vitro. Sera from vaccinated military personnel
      inhibited, and their PBMCs were partially resistant to, infection by HIV-1
      strains tropic to CCR5 (R5), but not to CXCR4 (X4), chemokine receptor.
      CONCLUSION: These findings demonstrate that increased anti-HIV chemokines can be
      detected in vaccine recipients up to 68 weeks following immunization.

PMID- 16965636
TI  - Discovery and validation of breast cancer subtypes.
AB  - BACKGROUND: Previous studies demonstrated breast cancer tumor tissue samples
      could be classified into different subtypes based upon DNA microarray profiles.
      The most recent study presented evidence for the existence of five different
      subtypes: normal breast-like, basal, luminal A, luminal B, and ERBB2+. RESULTS:
      Based upon the analysis of 599 microarrays (five separate cDNA microarray
      datasets) using a novel approach, we present evidence in support of the most
      consistently identifiable subtypes of breast cancer tumor tissue microarrays
      being: ESR1+/ERBB2-, ESR1-/ERBB2-, and ERBB2+ (collectively called the ESR1/ERBB2
      subtypes). We validate all three subtypes statistically and show the subtype to
      which a sample belongs is a significant predictor of overall survival and distant
      metastasis free probability. CONCLUSION: As a consequence of the statistical
      validation procedure we have a set of centroids which can be applied to any
      microarray (indexed by UniGene Cluster ID) to classify it to one of the
      ESR1/ERBB2 subtypes. Moreover, the method used to define the ESR1/ERBB2 subtypes
      is not specific to the disease. The method can be used to identify subtypes in
      any disease for which there are at least two independent microarray datasets of
      disease samples.

PMID- 16965635
TI  - Role of metabolically active hormones in the insulin resistance associated with
      short-term glucocorticoid treatment.
AB  - BACKGROUND: The mechanisms by which glucocorticoid therapy promotes obesity and
      insulin resistance are incompletely characterized. Modulations of the
      metabolically active hormones, tumour necrosis factor alpha (TNF alpha), ghrelin,
      leptin and adiponectin are all implicated in the development of these
      cardiovascular risk factors. Little is known about the effects of short-term
      glucocorticoid treatment on levels of these hormones. RESEARCH METHODS AND
      PROCEDURES: Using a blinded, placebo-controlled approach, we randomised 25
      healthy men (mean (SD) age: 24.2 (5.4) years) to 5 days of treatment with either
      placebo or oral dexamethasone 3 mg twice daily. Fasting plasma TNFalpha, ghrelin,
      leptin and adiponectin were measured before and after treatment. RESULTS: Mean
      changes in all hormones were no different between treatment arms, despite
      dexamethasone-related increases in body weight, blood pressure, HDL cholesterol
      and insulin. Changes in calculated indices of insulin sensitivity (HOMA-S,
      insulin sensitivity index) were strongly related to dexamethasone treatment (p <
      0.001). DISCUSSION: Our data do not support a role for TNF alpha, ghrelin, leptin
      or adiponectin in the insulin resistance associated with short-term
      glucocorticoid treatment.

PMID- 16965637
TI  - Risk factors for post-ICU red blood cell transfusion: a prospective study.
AB  - INTRODUCTION: Factors predictive of the need for red blood cell (RBC) transfusion
      in the intensive care unit (ICU) have been identified, but risk factors for
      transfusion after ICU discharge are unknown. This study aims identifies risk
      factors for RBC transfusion after discharge from the ICU. METHODS: A prospective,
      monocentric observational study was conducted over a 6-month period in a 24-bed
      medical ICU in a French university hospital. Between June and December 2003, 550
      critically ill patients were consecutively enrolled in the study. RESULTS: A
      total of 428 patients survived after treatment in the ICU; 47 (11% of the
      survivors, 8.5% of the whole population) required RBC transfusion within 7 days
      after ICU discharge. Admission for sepsis (odds ratio [OR] 341.60, 95% confidence
      interval [CI] 20.35-5734.51), presence of an underlying malignancy (OR 32.6,
      95%CI 3.8-280.1), female sex (OR 5.4, 95% CI 1.2-24.9), Logistic Organ
      Dysfunction score at ICU discharge (OR 1.45, 95% CI 1.1-1.9) and age (OR 1.06,
      95% CI 1.02-1.12) were independently associated with RBC transfusion after ICU
      stay. Haemoglobin level at discharge predicted the need for delayed RBC
      transfusion. Use of vasopressors (OR 0.01, 95%CI 0.001-0.17) and haemoglobin
      level at discharge from the ICU (OR 0.02, 95% CI 0.007-0.09; P < 0.001) were
      strong independent predictors of transfusion of RBC 1 week after ICU discharge.
      CONCLUSION: Sepsis, underlying conditions, unresolved organ failures and
      haemoglobin level at discharge were related to an increased risk for RBC
      transfusion after ICU stay. We suggest that strategies to prevent transfusion
      should focus on homogeneous subgroups of patients and take into account post-ICU
      needs for RBC transfusion.

PMID- 16965638
TI  - Information scanning--keeping in touch with best practice in breastfeeding.
AB  - This paper describes some of the methods practitioners can use to scan sources
      for up-to-date information about best practice in breastfeeding.

PMID- 16965639
TI  - Substance abuse treatment and psychiatric comorbidity: do benefits spill over?
      Analysis of data from a prospective trial among cocaine-dependent homeless
      persons.
AB  - BACKGROUND: Comorbid psychiatric illness can undermine outcomes among homeless
      persons undergoing addiction treatment, and psychiatric specialty care is not
      always readily available. The prognosis for nonsubstance abuse psychiatric
      diagnoses among homeless persons receiving behaviorally-based addiction
      treatment, however, is little studied. RESULTS: Data from an addiction treatment
      trial for 95 cocaine-dependent homeless persons (1996-1998) were used to profile
      psychiatric diagnoses at baseline and 6 months, including mood-related disorders
      (e.g. depression) and anxiety-related disorders (e.g. post-traumatic stress
      disorder). Treatment interventions, including systematic reinforcement for goal
      attainment, were behavioral in orientation. There was a 32% reduction in the
      prevalence of comorbid non-addiction psychiatric disorder from baseline to 6
      months, with similar reductions in the prevalence of mood (-32%) and anxiety
      related disorders (-20%) (p = 0.12). CONCLUSION: Among cocaine-dependent homeless
      persons with psychiatric comorbidity undergoing behavioral addiction treatment, a
      reduction in comorbid psychiatric disorder prevalence was observed over 6 months.
      Not all participants improved, suggesting that even evidence-based addiction
      treatment will prove insufficient for a meaningful proportion of the dually
      diagnosed homeless population.

PMID- 16965640
TI  - Reactive lymphoid hyperplasia of the liver in a patient with colon cancer: report
      of two cases.
AB  - BACKGROUND: Reactive lymphoid hyperplasia (RLH) of the liver is very rarely
      reported, and we encountered two cases of RLH of the liver in a patient with
      colon cancer. CASE PRESENTATION: In the first case, a 77-year-old woman was
      admitted for the surgical removal of a ascending colon cancer. A hepatic tumor in
      the left lobe was concurrently revealed by computed tomography (CT), and magnetic
      resonance imaging (MRI). The appearance suggested liver metastasis. Right
      hemicolectomy and partial hepatectomy were performed. On histopathological
      examination, lymphoid follicles with germinal centers were seen in the tumor-like
      lesion, and remarkable lymphoid infiltration with germinal centers was seen in
      the portal area around the nodule. Immunohistochemical studies revealed
      polyclonality of infiltrating lymphocyte. Consequently, this nodular lesion was
      diagnosed as RLH of the liver. In the second case, a 64-year-old woman who had a
      radical right hemicolectomy for stage II ascending colon cancer 10 years ago was
      admitted with dysuria. A hepatic tumor in the left lobe was concurrently revealed
      by CT and MRI, suggesting hepatocellular carcinoma. A left lateral segmentectomy
      was performed. Microscopically, this lesion revealed the almost same findings as
      the first case, so this nodular lesion was diagnosed as RLH of the liver.
      CONCLUSION: Our two cases were the first report of RLH of the liver accompanying
      colon cancer. Because there are a very few cases, so it is not clear whether the
      malignancies were involved in the onset of RLH. But we believe that new factors
      involved in the onset mechanism of RLH may be identified by carefully monitoring
      the clinical course of our two patients.

PMID- 16965641
TI  - Breast cancer risk associated with different HRT formulations: a register-based
      case-control study.
AB  - BACKGROUND: Previous epidemiological studies have inconsistently shown a modestly
      increased breast cancer risk associated with hormone replacement therapy (HRT).
      Limited information is available about different formulations--particularly
      concerning different progestins. METHODS: A case-control study was performed
      within Germany in collaboration with regional cancer registries and tumor
      centers. Up to 5 controls were matched breast cancer cases. Conditional logistic
      regression analysis was applied to estimate crude and adjusted odds ratios (OR)
      and 95% confidence intervals (95% CI). Stratified analyses were performed to
      compare the risk of different estrogens, progestins, and combinations. RESULTS: A
      total of 3593 cases of breast cancer were identified and compared with 9098
      controls. The adjusted overall risk estimate for breast cancer (BC) associated
      with current or past use of HRT was 1.2 (1.1-1.3), and almost identical for lag
      times from 6 months to 6 years prior to diagnosis. No significant trend of
      increasing BC risk was found with increasing duration of HRT use, or time since
      first or last use in aggregate. Many established BC risk factors significantly
      modified the effect of HRT on BC risk, particularly first-degree family history
      of BC, higher age, lower education, higher body mass index (BMI), and never
      having used oral contraceptives (OCs) during lifetime. Whereas the overall risk
      estimates were stable, the numbers in many of the sub-analyses of HRT formulation
      groups (estrogens, progestins, and combinations) were too small for strong
      conclusions. Nevertheless, the BC risk seems not to vary much across HRT
      formulation subgroups. In particular, no substantial difference in BC risk was
      observed between HRT containing conjugated equine estrogens (CEE) or
      medroxyprogesterone acetate (MPA) and other formulations more common in Europe.
      CONCLUSION: The BC risk of HRT use is rather small. Low risk estimates for BC and
      a high potential for residual confounding and bias in this observational study do
      not permit causal conclusions. Apparently, there is not much variation of the BC
      risk across HRT formulations (estrogens, progestins). However, the small numbers
      and the overlapping nature of some of the subgroups suggest cautious
      interpretation.

PMID- 16965642
TI  - Amphotericin B nasal spray has no effect on nasal polyps.
AB  - Nasal polyps and chronic rhinosinusitis are the products of an inflammatory
      process. Recently, fungal involvement has been thought to stimulate the
      development of polyps, and administration of antifungal agents was therefore
      considered a potential treatment. Several studies have been published indicating
      amphotericin B as an effective treatment for nasal polyps and chronic
      rhinosinusitis. The aim of our investigation was to evaluate the efficacy of
      intranasal applied amphotericin B on the growth of nasal polyps in a three-month,
      prospective, open trial. Our results show that nasal amphotericin B spray is not
      effective for nasal polyps and may even cause deterioration.

PMID- 16965643
TI  - [Inducement of tumor cell autophagy and cell cycle analysis].
AB  - BACKGROUND & OBJECTIVE: Autophagy is the main phenomenon of type II programmed
      cell death which is also named as autophagic cell death, and autophagy has a
      close relationship with autophagic cell death. The relationship of apoptosis and
      cell cycle has been explored deeply, but little is known about the relationship
      of autophagic cell death and cell cycle. This study was to observe the
      correlation of autophagy induced by different methods to cell cycle. METHODS:
      Exponentially growing HeLa and SW480 cells, and peripheral blood lymphocytes
      (PBLs) from healthy donors, with or without 48 h stimulation of
      phytohemagglutinin (PHA), were treated with Hanks' solution (to produce
      starvation) or vincristine. Confocal laser microscope and transmission electron
      microscope (TEM) were used to detect autophagy; flow cytometry (FCM) was
      innovatively used to detect the cell cycle of autophagic cells with dipl
      parameters of microtubule-associated protein 1 light chain 3 (MAP1-LC3-II)/PI.
      RESULTS: Autophagy of HeLa and SW480 cells induced by starvation or vincristine
      was observed in G1, S, and G2/M phases and increased along with the inducement
      time; no autophagy was observed in unstimulated PBLs. The positive rate of LC3
      II, indicating the occurrence of autophagy, was lower than 2.62% when induced by
      starvation in Hanks' solution for 48 h, or 6.16% when induced by vincristine for
      48 h. After PBLs were stimulated into cell cycle by PHA, autophagy was markedly
      detected 2 h after the indicated inducements. CONCLUSIONS: MAP1-LC3-II/DNA dipl
      parameter analysis by FCM is a convenient and reliable method for simultaneously
      analyzing autophagy and cell cycle. Autophagy could be induced when cells are in
      cell cycle, while the cells in G0 phase are insensitive to the inducers.

PMID- 16965644
TI  - [Effect of T-bet on biological functions of mouse macrophage Raw264.7].
AB  - BACKGROUND & OBJECTIVE: T-bet (T box expressed in T cells), a Th1-specific T box
      transcription factor, controls many kinds of immune cells, such as Th1, NK, CD8+,
      dendritic cells, and B cells. This study was to explore potential effects of T
      bet gene on biological functions of mouse macrophage Raw264.7 cells in vitro.
      METHODS: The eukaryotic expression vector carrying mouse T-bet (pcDNA3.0-mT-bet)
      was constructed and identified by consequence analysis, double restrictive
      endonucleases digestion and polymerase chain reaction (PCR). The gene expression
      in Raw264.7 cells was detected by reverse transcription-polymerase chain reaction
      (RT-PCR) and Western blot. PBS, pcDNA3.0, and pcDNA3.0-mT-bet were transiently
      transfected into Raw264.7 cells respectively; cell cycle, MHC I/II expression
      levels, phagocytic activity of FITC-dextran, nitric oxide (NO) secretion level,
      and the cytotoxicity of Raw264.7 cells to mouse leukemia cell line L1210 were
      evaluated 48 hours after transfection. RESULTS: Eukaryotic expression vector
      which could express T-bet protein in Raw264.7 cells was successfully constructed.
      There was no difference in cell cycle between pcDNA3.0 group and pcDNA3.0-mT-bet
      group. There was significant difference in MHC I expression level between
      pcDNA3.0 group (20.8+/-0.7) and pcDNA3.0-mT-bet group (24.8+/-0.6, P<0.05), but
      not in MHC II expression level; there was also difference in mean fluorescence
      intensity of phagocytized dextran between pcDNA3.0 group (28.2+/-0.4) and
      pcDNA3.0-mT-bet group (32.8+/-0.8, P<0.05); there was also significant difference
      in NO secretion level between pcDNA3 group (0 pmol) and pcDNA3.0-mT-bet group
      [(1.7+/-0.6) pmol, P<0.05] without lipopolysaccharide (LPS) stimulation;
      meanwhile, significant difference was also observed between pcDNA3.0 group [(10.5
      +/-1.3) pmol] and pcDNA3.0-mT-bet group [(15.6+/-1.6) pmol, P<0.05] under the
      stimulation of LPS (10 microg/ml) for 20 h; there was also difference in
      cytotoxicity of Raw264.7 cells to L1210 cells in vitro between pcDNA3 group
      [(35.6+/-2.1)%] and pcDNA3.0-mT-bet group [(51.9+/-3.5)%, P<0.05]. CONCLUSION: T
      bet up-regulates MHC I expression and NO secretion level in Raw264.7 cells,
      increases their cytotoxicity to L1210 cells, but has no influences on the cell
      cycle and MHC II expression.

PMID- 16965645
TI  - [Effect of vascular endothelial growth factor antibody Avastin on angiogenesis of
      human gastric cancer growing orthotopically in nude mice].
AB  - BACKGROUND & OBJECTIVE: The failure to treat gastric cancer is often due to the
      recurrence or dismal metastasis of cancer and the poor response to traditional
      chemotherapeutic or radiotherapeutic regimens. Vascular endothelial growth factor
      (VEGF) is related closely to the growth and metastasis of gastric cancer. This
      study was to examine the effects of Avastin, a monoclonal antibody developed
      against VEGF, with or without 5-fluorouracil (5-FU) on the growth, metastasis,
      and angiogenesis of a gastric cancer model. METHODS: A metastasis model of human
      gastric cancer was established by orthotopic transplantation of histologically
      intact human tumor tissue blocks in the gastric walls of nude mice. All mice were
      randomly divided into 4 groups: control group, 5-FU group, Avastin group, and
      combination treatment group. Forty-two days after treatment, tumor weight,
      inhibition rates, intratumoral microvessel density, apoptosis index, and presence
      of metastasis were evaluated. RESULTS: Combination therapy with 5-FU and Avastin
      augmented the reduction of primary tumor growth and inhibited metastasis compared
      with treatment with either agent alone. After treatment with Avastin plus 5-FU, a
      significant increase in apoptotic tumor cells and a decrease in microvessel
      density were observed. CONCLUSIONS: Avastin plus 5-FU can induce apoptosis in
      gastric cancer cells and has strong inhibitory effects on tumor growth and the
      metastasis to the liver. Anti-VEGF therapy in combination with traditional
      chemotherapy may be a novel therapeutic approach for advanced gastric cancer.

PMID- 16965646
TI  - [Immunotherapeutic effects of beta-elemene combined with interleukin-23 gene
      modified dendritic cells on murine pancreatic carcinoma].
AB  - BACKGROUND & OBJECTIVE: Dendritic cell (DC) vaccine is a kind of treatment
      vaccine with clinical application potency. Functional cytokines can enhance anti
      tumor immune response of dendritic cells. This study was to investigate the
      protective effects on murine pancreatic carcinoma by beta-elemene combined with
      bone marrow-derived dendritic cells (BM-DCs) modified with murine interleukin
      (IL)-23 gene. METHODS: The murine IL-23 cDNA was sub-cloned into dual-expression
      vector. DCs were pulsed with tumor cell lysate after modified by IL-23 gene. Mice
      were injected with IL-23-transfected DC vaccine, non-transfected DC vaccine, and
      sodium, respectively. The immune preventative and immunotherapeutic effects of DC
      vaccines on mice and the cytokine release in vivo were assessed. Effects of
      vaccine combined with beta-elemene on tumor growth and survival period of the
      mice were observed. RESULTS: IL-23 protein apparently increased the antigen
      presenting ability of DCs. After the vaccination of DC vaccines, IFN-gamma
      production in treatment group was significantly more than that of the control
      group (P<0.01), as well as, IL-4 production was less than that in the normal
      group (P<0.05). Tumor growth was obviously inhibited and the survival period of
      the mice was obviously prolonged in beta-elemene combined with DC vaccine group
      than in DC, beta-elemene, or control group (P<0.01). CONCLUSIONS: IL-23-modified
      DC vaccines can enhance specific Th1-type and CTL response against pancreatic
      carcinoma cells, induce not only preventative immunity, but also auto-immunity
      against pancreatic carcinoma. Moreover, beta-elemene has great collaborative anti
      tumor function.

PMID- 16965647
TI  - [Treatment of murine Lewis lung cancer with recombinant interleukin-12].
AB  - BACKGROUND & OBJECTIVE: Interleukin-12 (IL-12) is a proinflammatory cytokine with
      antitumor activity. The study was to compare the therapeutic effects of
      recombinant murine interleukin-12 (mIL-12) plasmid [pcDNA3.1(+)-mIL-12] and Lewis
      lung carcinoma (LLC) cell line which could stably express mIL-12 gene in LLC.
      METHODS: The recombinant plasmid was transfected into LLC cells with lipofectin
      to obtain LLC/mIL-12 cells which stably express mIL-12 gene. Tumors were
      established on the right hind leg of C57 BL/6 mice by the subcutaneous injection
      of 2 x 106 LLC cells. Then all mice were divided into 4 groups (n=10) randomly
      when the tumors reached 0.5-1.0 cm in diameter. Subsequently, the mice were
      treated by intratumor injection of pcDNA3.1(+)-mIL-12 plasmid or LLC/mIL-12
      vaccine on the first, fourth, and seventh days. Tumor size was measured before
      and after treatment. Tumor growth curve, CTL and NK activity of spleen cells, and
      tumor lymphocyte infiltration were observed after all mice were killed on the
      fourteenth day. RESULTS: Tumor growth were inhibited in mice treated with
      pcDNA3.1(+)-mIL-12 plasmid or LLC/mIL-12 vaccine; the NK and CTL cell activity
      was augmented by mIL-12. Overall, the effects were more satisfactory in vaccine
      group than in plasmid group. There was abundant CD4+ and CD8+ T lymphocyte
      infiltration observed in both groups. CONCLUSION: mIL-12 in LLC cell line can
      increase NK cells and CTL. Antitumor immune response could be induced both by
      pcDNA3.1(+)-mIL-12 plasmid and by LLC/mIL-12 vaccine; the latter one could induce
      stronger response.

PMID- 16965648
TI  - [Radiofrequency ablation combined with ethanol injection for liver cancer
      treatment---an experimental study].
AB  - BACKGROUND & OBJECTIVE: Radiofrequency ablation (RFA), which is widely used in
      treating primary and secondary liver cancer, is regarded as one of the most
      effective and promising regional therapies to date. However, limited necrosis
      region and high local recurrence are the major disadvantages of RFA. Researches
      on RFA are mostly focused on how to widen necrosis regions and decrease local
      recurrence. This study was to investigate whether RFA combined with ethanol
      injection (PEI) would widen necrosis region. METHODS: Ex-swine and rabbit VX2
      liver cancer models were used for in vitro and in vivo experiments, respectively.
      Four groups of each model were treated with RFA, PEI, RFA-PEI, and PEI-RFA,
      respectively. The size, shape, and volume of necrosis lesions, parameters (time
      and power) of RFA, and adverse events in the 4 groups were analyzed. RESULTS: In
      in vitro study, compared with those of groups PEI, RFA, and RFA-PEI, the mean
      size of necrosis regions in group PEI-RFA was significantly larger (2.05 cm x
      2.35 cm vs. 0.63 cm x 1.45 cm, 1.58 cm x 1.94 cm, 1.63 cm x 2.02 cm, P <0.05);
      the mean volume was greater [(6.33+/-2.86) cm(3) vs. (0.33+/-0.18) cm(3), (3.21+/
      1.18) cm(3), (3.67+/-1.58) cm(3); P <0.05], and the isoperimetric ratio (parallel
      diameter/vertical diameter) was closer to 1.0 (0.87 vs. 2.36, 0.82, 0.80; P
      <0.05). In in vivo study, compared with those of groups PEI, RFA, and RFA-PEI,
      the mean size of necrosis regions in group PEI-RFA was significantly larger (1.92
      cm x 2.22 cm vs. 1.00 cm x 1.56 cm, 1.17 cm x 1.55 cm, 1.23 cm x 1.64 cm; P
      <0.05); the mean volume was greater [(5.26+/-2.22) cm(3) vs. (0.93+/-0.61) cm(3),
      (1.60+/-0.87) cm(3), (1.90+/-1.15) cm(3); P <0.05], and the isoperimetric ratio
      was closer to 1.0 (0.87 vs 1.61, 0.75, 0.75; P <0.05). CONCLUSION: RFA following
      PEI (PEI-RFA) increases the size and volume of necrosis region significantly, and
      makes the shape of necrosis region more similar to that of small liver cancer.

PMID- 16965649
TI  - [Radiosensitization of nasopharyngeal carcinoma cell line CNE1 by inhibiting the
      expression of ATM/PI3K functional region].
AB  - BACKGROUND & OBJECTIVE: It is reported that ATM gene is closely correlated to
      cellular radiosensitivity in several malignant tumors. Suppression of ATM protein
      expression leads to cellular radiosensitization. This study was to determine
      whether this effect also exists in nasopharyngeal carcinoma (NPC) cell line CNE1
      by inhibiting the expression of ATM protein through antisense RNA of ATM/PI3K
      region, which is the most important functional fragment of ATM gene. METHODS: The
      recombinant pDOR-atm expressing antisense RNA of ATM/PI3K segment was constructed
      with retroviral vector pDOR. CNE1 cells were stably transfected with pDOR-atm by
      cationic liposome and named CNE1/pDOR-atm. Semi-quantitive RT-PCR was used to
      detect the level of ATM mRNA. Flow cytometry (FCM) was employed to analyze the
      percentage of positive cells and mean fluorescence density of protein expressing
      ATM. Cellular radiosensitivity was evaluated by colony survival assay (CSA) and
      linear-quadratic model in both CNE1/ pDOR-atm and control cells. RESULTS: The
      level of ATM mRNA index (RI) was 0.23+/-0.02 in CNE1/pDOR-atm group, and 0.51+/
      0.03 in control group (P<0.05). The percentage of positive cells and mean
      fluorescence density of proteins expressing ATM were 70.8% and 1.81+/-0.12 in
      CNE1/pDOR-atm group, while 99.3% and 4.51+/-0.18 in control group(P<0.01). The
      expression of ATM mRNA and protein was inhibited by antisense RNA. The alpha
      value (one function from linear-quadratic model) of CNE1/pDOR-atm group was 0.40
      Gy(-1), while it was 0.36 Gy(-1) in control group. The radiosensitizing ratio of
      surviving fraction at 2 Gy (SF(2)) was 3.0, indicating that antisense RNA group
      was more radiosensitive to X-ray than the controls. CONCLUSION: NPC cell line
      CNE1 could be radiosensitized by the down-regulation of ATM/PI3K expression.

PMID- 16965651
TI  - [Photodynamic effect of hematoporphyrin monomethyl ether on ovarian cancer cell
      line SKOV3].
AB  - BACKGROUND & OBJECTIVE: Photodynamic therapy (PDT) is a new treatment choice for
      ovarian carcinoma. Hematoporphyrin monomethyl ether (HMME) is a novel
      photosensitive reagent developed in China. This study was to investigate the
      photodynamic effect of HMME-based PDT on human epithelial ovarian cancer cell
      line SKOV3. METHODS: After an incubation with 30 microg/ml HMME for different
      time, the fluorescent image and intracellular location of HMME in SKOV3 cells
      were observed under a fluorescent microscope and laser scanning confocal
      microscope (LSCM). After being treated with different doses (5-50 microg/ml) of
      HMME and irradiated with different optical doses (1.5-12 J/cm(2)) of laser, the
      survival rate of SKOV3 cells was measured by MTT assay. Mechanisms of cell death
      during PDT was determined by Annexin V/PI double staining technique and analyzed
      by flow cytometry. RESULTS: Red fluorescence appeared shortly after
      administration of HMME and localized in cytoplasm; intracellular fluorescence
      intensity reached the peak after 3 h. High concentrations of HMME alone had
      cytotoxicity to SKOV3 cells, while laser irradiation alone had no effect on cell
      survival. Survival rate of SKOV3 cells was gradually decreased along with the
      increase of HMME concentration and laser dose, but such a trend diminished when
      HMME concentration reached 40 microg/ml. After treatment of HMME, the dead cells
      were predominantly necrosis cells. CONCLUSION: HMME has a photodynamic effect on
      SKOV3 cells.

PMID- 16965650
TI  - [Biological and antitumor effects of CD40L on ovarian cancer cell line OVHM].
AB  - BACKGROUND & OBJECTIVE: Accumulative evidences have indicated the importance of
      CD40-CD40L receptor-ligand pair in the initiation and regulation of human immune
      response. Whether triggering CD40-CD40L signaling pathway could induce antitumor
      effects in ovarian cancer cells is still unclear. This study was to investigate
      the biological and antitumor effects of CD40L on ovarian cancer cell line OVHM
      (CD40-positive). METHODS: CD40L cDNA was transfected into OVHM cells by
      lipofectamine 2000. Immunofluorescent technique and flow cytometry were used to
      evaluate the expression of CD40, CD40L, MHC-I, MHC-II, CD80, CD86. Cell
      proliferation was detected by MTT assay. CD40L/OVHM and OVHM cells were
      inoculated hypodermically into C57BL/6N x C3H/He F1 (B6C3F1) mice and BALB/c nude
      mice simultaneously. Tumor volume was measured. The production of IFN-gamma
      secreted by the spleen cells from CD40L/OVHM and OVHM cell-inoculated mice co
      cultured with 20 Gy-irridiated OVHM cells were measured with enzyme-linked
      immunosorbent assay (ELISA). RESULTS: Expression of CD40L in OVHM/CD40L cells was
      significantly higher than that in OVHM cells (P<0.05). Moreover, the expression
      of co-stimulatory molecules CD80 and CD86 of CD40L/OVHM was increased (P<0.05).
      The proliferation rate of parental and CD40L-expressed OVHM cells were not
      different. Although, delayed tumor growth was observed when CD40L-expressing OVHM
      cells and OVHM cells were injected simultaneously and contralaterally, the tumor
      growth of OVHM and CD40L/OVHM in BALB/c nude mice was not different. The amounts
      of IFN-gamma secreted by the co-culture of irradiated OVHM cells with spleen
      cells from mice injected with CD40L/OVHM were much higher than those from
      OVHM/parental cell inoculated and naive mice. CONCLUSION: The forced expression
      of CD40L cDNA in OVHM cells can increase the immunogenicity, and thus develop
      antitumor effects against OVHM-incubated mice. In vivo immunization of
      immunocompetent mice with CD40L/OVHM improves the generation of cytotoxic
      lymphocytes against parent ovarian cancer cells.

PMID- 16965652
TI  - [Correlation of XPC Ala499Val and Lys939Gln polymorphisms to risks of esophageal
      squamous cell carcinoma and gastric cardiac adenocarcinoma].
AB  - BACKGROUND & OBJECTIVE: Xeroderma pigmentosum group C(XPC) gene is involved in
      nucleotide excision repair (NER). Single nucleotide polymorphisms (SNP) in XPC
      gene may affect DNA repairing capacity and genetic susceptibility to cancer. This
      study was to investigate the correlation of XPC exon 8 Ala499Val and exon 15
      Lys939Gln SNPs to the susceptibility of esophageal squamous cell carcinoma (ESCC)
      and gastric cardiac adenocarcinoma (GCA) in a population at a high incidence
      region of Hebei Province. METHODS: XPC exon 8 Ala499Val and exon 15 Lys939Gln
      SNPs were genotyped by polymerase chain reaction-restrictive fragment length
      polymorphism (PCR-RFLP) analysis in 327 ESCC patients, 253 GCA patients, and 612
      healthy controls. RESULTS: The number of the subjects with family history of
      upper gastrointestinal cancer (UGIC) was significantly higher in ESCC and GCA
      groups than in control group. Family history of UGIC may increase the risk of
      developing ESCC and GCA [age and gender adjusted odds ratio (OR) =1.76 and 1.77,
      95% confidence interval (CI) = 1.34-2.32 and 1.31-2.39]. The overall allelotype
      and genotype distributions of XPC exon 8 Ala499Val in ESCC patients were not
      significantly different from those in healthy controls (P>0.05). T allelotype
      frequency of XPC exon 8 in GCA patients was 26.5%, which was significantly lower
      than that in healthy controls (Chi2=6.12, P=0.01). The C/T genotype frequencies
      of XPC exon 8 in GCA patients and healthy controls were 35.6% and 46.1%
      respectively. Compared with individuals with C/C genotype, individuals with C/T
      genotype had significantly lower risk in developing GCA (OR=0.62, 95% CI=0.45
      0.84). When stratified for smoking status and family history of UGIC, compared
      with individuals with C/C genotype, individuals with C/T genotype in smoker group
      and in the group without family history of UGIC had lower risk in developing GCA
      (OR=0.57, 95% CI=0.36-0.91 and 0.37-0.88). The overall allelotype and genotype
      distributions of XPC exon 15 Lys939Gln in ESCC and GCA patients were not
      significantly different from those in healthy controls (P>0.05). When stratified
      for smoking status and family history of UGIC, compared with individuals with A/A
      genotype, individuals in non-smoker group with C/C genotype had higher risk in
      developing ESCC (OR=2.05, 95% CI=1.15-3.66). The haplotype distribution of ESCC
      patients was not significantly different from that of healthy controls (P>0.05),
      while the haplotype distribution of GCA patients was significantly different from
      that of healthy controls (P=0.02). Compared with A/T haplotype, A/C and C/C
      haplotypes significantly increased the risk of developing GCA (OR=1.35 and 1.46,
      95% CI=1.01-1.81 and 1.06-2.00). CONCLUSIONS: In the high incidence region of
      Hebei Province, C/T genotype of XPC exon 8 may decrease the risk of developing
      GCA. Lys939Gln SNP in exon 15 may have no influence on the risk of ESCC and GCA,
      but when stratified for smoking status, C/C genotype of XPC exon 15 may increase
      the risk of developing ESCC in non-smoking population. While A/C and C/C
      haplotypes may increase the risk of developing GCA.

PMID- 16965653
TI  - [High-dose induction therapy followed by maintenance with recombinant human
      erythropoietin for 30 patients with tumor-related anemia].
AB  - BACKGROUND & OBJECTIVE: Anemia is a common complication of cancer patients.
      Recombinant human erythropoietin (rhEPO) can alleviate the symptoms of cancer
      related anemia. However, the optimal use of rhEPO is still on investigation. This
      study was to find out the optimal use of rhEPO in anemic cancer patients
      undergoing chemotherapy. METHODS: From May, 2004 to Feb, 2005, 30 patients with
      cancer-related anemia receiving concurrent chemotherapy were enrolled. This open
      labeled, non-randomized, and pilot study evaluated the response rate of induction
      rhEPO 120,000 U (40,000 U was subcutaneously injected on d1, 3, 5) followed by
      subcutaneous injection of maintenance dose of 40,000 U once a week for 3 weeks
      (d8, 15, 22). Hemoglobin (Hb) and hematocrit (Hct) were measured before treatment
      and fortnightly during the treatment. RESULTS: Mean Hb maintained increasing
      during treatment. In week 2 (n=29) and week 4 (n=21), there were 27.59% and
      61.90% patients, respectively, whose Hb value had increased more than 20 g/L from
      the baseline (79.56 g/L) and mean Hb were 90.26 g/L and 96.81 g/L respectively
      (P<0.05). And mean Hct at week 2 and week 4 were 27.01% and 30.17% respectively,
      which were higher than the baseline (24.29%)(P=0.062 and 0.001 respectively). All
      patients demonstrated fine tolerance. CONCLUSION: Induction therapy followed by
      maintenance with rhEPO can improve the level of hemoglobin significantly and
      quickly in anemic cancer patients.

PMID- 16965654
TI  - [Surgical treatment efficacy of bronchioloalveolar carcinoma: a retrospective
      analysis of 130 patients].
AB  - BACKGROUND & OBJECTIVE: Bronchioloalveolar carcinoma (BAC) is a well
      differentiated lung adenocarcinoma occurring in the periphery of the lung and
      growing along an intact interstitial framework. There are controversies about the
      surgical treatment efficacy of BAC. This study was to explore the surgical
      treatment efficacy of BAC. METHODS: Data were collected from 130 patients with
      BAC, hospitalized in the department of Thoracic Surgery, Cancer Center of Sun Yat
      sen University, diagnosed by postoperative pathology from 1985 to 2000. Clinical
      and histological features, approaches and outcomes of surgical treatment
      according to different TNM stages and clinical patterns were studied
      retrospectively. RESULTS: Of the 130 patients, 56.1% were men, 42.9% were women.
      The ratio of smoker to non-smoker was 1:1.55. Ninety-eight patients underwent
      complete resection and 32 underwent incomplete resection. Patients in stage I
      (n=54), stage II (n=15), stage III B (2/11), and stage IV (1/19) underwent
      complete resection, of whom the 5-year survival rates were 60.7%, 33.3%, 13.6%,
      and 14.0%, respectively. Patients of unifocal (96/113), multifocal (1/12), and
      pneumonic (1/19) patterns underwent complete resection, of whom the median
      survival time was 46.3, 20.6, and 5 months. The 1-, 3-, and 5-year survival rates
      were 96.4%, 58.6%, and 41.2% for the unifocal pattern, 91.2%, 41.7%, and 33.3%
      for the multifocal pattern, 20%, 0, and 0 for the pneumonic pattern. CONCLUSION:
      Complete surgical resection can achieve favorable survival rates for BAC in stage
      I/II and multifocal BAC in stage III/IV, whereas relatively poorer prognosis for
      pneumonic BAC.

PMID- 16965655
TI  - [Clinical features and diagnosis of pulmonary lymphangitic carcinomatosis].
AB  - BACKGROUND & OBJECTIVE: Pulmonary lymphangitic carcinomatosis (PLC) is a special
      type of pulmonary metastasis of carcinoma. It is easy to be misdiagnosed as other
      pulmonary interstitial diseases. This study was to discuss the clinical features
      of PLC, and provide experience information for diagnosis, differentiated
      diagnosis, and evaluation of prognosis of PLC. METHODS: A retrospective
      comparison analysis was performed on 43 PLC patients with pathologic diagnosis
      and 46 patients with other pulmonary interstitial diseases with clear etiology in
      the first affiliated hospital of Sun Yat-sen University within the past decade.
      RESULTS: In PLC group, 20 patients were found with primary lung cancer; 23
      patients were found with primary non-pulmonary carcinoma: 9 cases of breast
      cancer, 8 cases of large intestinal carcinoma, and 6 cases of gastric carcinoma.
      The changes of imaging included linear and radiating appearances from the hilum
      to the outer part even extending to the pleura with nodules, ground-glass opacity
      of the lung. Enlargement of lymph nodes in mediastinum was present in 51.2%
      (22/43) and that in pleural effusion was present in 53.5% (23/43) of patients.
      Extrapulmonary manifestations (metastasis) included 19 cases (44.2%) of lymph
      nodes to the supraclavicular region, axillary fossa, and post-peritoneal region,
      15 cases (34.9%) to the pleura, 9 cases (20.9%) to the bones, 6 cases (14.0%) to
      the liver, 3 cases (7.0%) to the pericardium, and 3 cases (7.0%) to the brain.
      The elevated serum level of CEA was commonly observed (23/43, 53.5%). Respiratory
      manifestations of PLC, such as coughing, panting, dyspnea, and so on, could not
      be cured by anti-spasm treatment. The development of PLC was so progressive that
      31 patients (72.1%) were followed for only 2-7 months before death. The changes
      of imaging in other pulmonary interstitial disease group included irregular
      linear or reticular appearances, enlargement of lymph nodes in the mediastinum
      and hilum, and extrapulmonary manifestations like pleural effusion were not
      observed. Respiratory manifestations, such as coughing, panting, dyspnea, and so
      on, could be cured by anti-spasm treatment. Moreover, the development of PLC was
      relatively slow. CONCLUSIONS: PLC often occurs in patients with primary carcinoma
      in lung, breast, large intestine, stomach, and so on. More attention should be
      paid to the diagnosis of PLC in patients who have pulmonary interstitial lesions
      as described above, and whose respiratory symptoms could not be relieved by anti
      spasm treatment and developed progressively. The prognosis of PLC is poor.

PMID- 16965656
TI  - [Extrapulmonary small cell carcinoma in 52 patients].
AB  - BACKGROUND & OBJECTIVE: The majority of small cell carcinoma occurs in the lung.
      Extrapulmonary small cell carcinoma (ESCC) has been recognized as a
      clinicopathologic entity distinct from small cell carcinoma of the lung. The
      study was to investigate the clinical characteristics, therapy, and prognosis of
      ESCC. METHODS: The medical records, from Jan. 1985 to Dec. 2005, of 53 patients
      with pathologically proved ESCC were analyzed retrospectively. RESULTS: Of the 53
      patients, 39 were men and 14 were women, with the median age of 53 years (range,
      27-76 years). Of the 53 cases of ESCC, 33 (62.3%) were detected in the esophagus,
      5 in the cervix, 4 in the larynx, 3 in the pharynx, 2 in the upper sinus, 2 in
      the rectum and sublingual gland, 1 in the thyroid gland, 1 in the pleura, and 1
      in the liver. Forty patients (75.5%) had limited disease (LD) and 13 (24.5%) had
      extensive disease (ED). Patients with ED mostly received platinum-based
      chemotherapy, for which the response rate was 69.2%. Patients with LD were
      treated with a variety of therapeutic modalities: 7 were treated with surgery
      plus radiochemotherapy, 3 with surgery plus radiotherapy, 18 with surgery plus
      chemotherapy, 6 with radiotherapy plus chemotherapy, 4 with radiotherapy alone,
      and 2 with chemotherapy alone. The median survival time (MST) was 20 months for
      all patients, and the 1-and 3-year survival rates were 41.3% and 31.4%. MST for
      patients with ED and LD were 15 months and 26 months, respectively, and 1-and 3
      year survival rates were 51.1% vs. 14.4%, and 42.5% vs. 0% (P=0.017 ).
      CONCLUSIONS: ESCC is identified in various sites, with the most common primary
      site being the esophagus. Multimodality therapy has become increasingly used for
      the majority of patients with LD-ESCC. Combination chemotherapy has been a major
      treatment for patients with ED-ESCC. Generally, the prognosis of LD-ESCC is
      significantly superior to ED-ESCC.

PMID- 16965657
TI  - [Correlations of S100A4 protein expression to invasion and metastasis of non
      small cell lung cancer].
AB  - BACKGROUND & OBJECTIVE: Metastasis-associated protein S100A4 is overexpressed in
      many malignant tumor cells; it may play a pivotal role in invasion and metastasis
      of malignant tumors. This study was to determine the expression of S100A4 in
      human non-small cell lung cancer (NSCLC), and to investigate its correlations to
      invasion and metastasis of NSCLC. METHODS: The expression of S100A4 in 41
      specimens of NSCLC and 6 specimens of normal lung tissues was detected by SP
      immunohistochemistry. The correlations of S100A4 to clinicopathologic features of
      NSCLC were analyzed. RESULTS: The positive rate of S100A4 was significantly
      higher in NSCLC than in normal lung tissues (70.7% vs. 16.7%, P<0.05), and was
      significantly higher in adenocarcinoma than in squamous cell carcinoma (90.0% vs.
      52.4%, P<0.01). The positive rate of S100A4 was significantly higher in stage III
      IV than in stage II and stage I NSCLC (100.0% vs. 66.7% and 30.0%, P<0.01), while
      there was no obvious difference between the latter 2 groups (P>0.05). The
      positive rate of S100A4 was significantly higher in NSCLC with lymphatic
      metastasis than in NSCLC without lymphatic metastasis (90.0% vs. 52.4%, P<0.01),
      and significantly higher in NSCLC with tumor size of > or = 3 cm than in NSCLC
      with tumor size of < 3 cm (91.3% vs. 44.4%, P<0.001). The expression of S100A4
      was closely related to lymphatic metastasis (r=0.480, P=0.001), and tumor size
      (r=0.288, P=0.017). No significant correlation was found between the expression
      of S100A4 and pathologic grade of NSCLC (P>0.05). CONCLUSION: S100A4 expression
      is up-regulated in NSCLC, and closely related to lymphatic metastasis, TNM stage
      and tumor size, which suggest an important role of S100A4 in the invasion and
      metastasis of NSCLC.

PMID- 16965658
TI  - [Prognostic analysis of adenoid cystic carcinoma of major salivary glands of 64
      cases].
AB  - BACKGROUND & OBJECTIVE: Adenoid cystic carcinoma of salivary glands is a kind of
      highly malignant tumor, and researches on the tumors originated from major
      salivary glands are rare. This study was to investigate prognostic factors of
      adenoid cystic carcinoma of major salivary glands. METHODS: Clinical records of
      64 patients with adenoid cystic carcinoma of major salivary glands followed up
      for more than 7 years were reviewed. Cumulative survival rate was analyzed by the
      Kaplan-Meier method. The log-rank test was applied to compare survival rates, and
      the comparison of the percentage of subjects between two groups was conducted
      with Chi2 test. RESULTS: The overall death rate was 57.8%; the cause-specific
      death rate was 46.9%; the 5-and 10-year cumulative survival rates were 65.63% and
      54.52%, respectively; the relapse rate was 34.4%; and the metastasis rate was
      45%. Univariate analysis revealed that the factors impacting the prognosis were
      age, presence or absence of nerve invasion, histological subtypes, clinical
      stage, positive or negative surgical margin. Patients aged > or = 50, presence of
      nerve invasion, solid/tubular subtype, advanced clinical stage (stages III and
      IV), and positive surgical margin had poorer prognosis than those aged < 50,
      absence of nerve invasion, cribriform subtype, early clinical stage (stages I and
      II), and negative surgical margin. Multivariate analysis showed that the presence
      of nerve invasion, solid histological subtype, advanced clinical stage (stages
      III and IV), and positive surgical margin were independently associated to poor
      prognosis. CONCLUSION: Presence or absence of nerve invasion, histological
      subtype, clinical stage, and positive or negative surgical margin are the
      independent factors affecting the prognosis of patients with adenoid cystic
      carcinoma of salivary glands.

PMID- 16965659
TI  - [Clinical analysis of salivary malignant pleomorphic adenoma--a report of 95
      cases].
AB  - BACKGROUND & OBJECTIVE: Malignant pleomorphic adenoma is rare with extensive
      location, which makes it difficult to evaluate the efficacy of the treatments.
      This study was to summarize the clinical features of salivary malignant
      pleomorphic adenoma, and thus to explore the treatment principle and efficacy of
      the treatment. METHODS: Clinical data of 95 salivary malignant pleomorphic
      adenoma patients, treated in Cancer Center, Sun Yat-sen University from May 1970
      to Oct. 2000, were analyzed retrospectively. The overall cumulative survival rate
      was estimated using life table method by SPSS10.0 software. Survival curves were
      compared with Gehan method. RESULTS: The 5-, 10-, and 15-year overall survival
      rates of the 95 patients were (64.9+/-4.9)%, (56.3+/-5.4)%, and (47.8+/-6.1)%,
      respectively. The 5-and 10-year disease-specific survival rates for the patients
      received surgery (51 cases), surgery plus radiotherapy (35 cases) were 76.1%,
      63.7% and 69.9%, 50.8%, respectively, but the 5-and 10-year disease-specific
      survival rates for the patients received radiotherapy only, chemotherapy only and
      radiochemotherapy (4 cases) were all 0. CONCLUSIONS: Surgery or surgery-dominated
      multi-modality are the principal treatment modalities for salivary malignant
      pleomorphic adenoma. The efficacy of surgery and surgery plus radiotherapy is
      better than non-surgery treatments.

PMID- 16965660
TI  - [Multivariate regressive analysis of prognosis of liver metastases from
      colorectal cancer].
AB  - BACKGROUND & OBJECTIVE: It is not very clear about the factors that affect the
      prognosis of liver metastases from colorectal cancer. This study was to
      investigate the clinicopathologic factors related to the prognosis of liver
      metastases from colorectal cancer. METHODS: The clinicopathologic factors and
      follow-up data of 197 patients with liver metastases from colorectal cancer,
      treated from Jan. 1996 to Dec. 2000, were analyzed retrospectively. The
      prognostic index (PI) of patients was calculated based on the results of
      multivariate analysis and patients were classified into different hazard groups
      accordingly. RESULTS: The overall 1-, 3-, and 5-year survival rates were 59.04%,
      17.73%, and 11.48%. Univariate analysis revealed that extrahepatic invasion,
      primary tumor resection, liver metastasis resection, type of primary tumor, serum
      CEA concentration, number and size of liver metastases, and distribution of liver
      metastases were associated with prognosis. Multivariate analysis identified that
      the resection of liver metastases, serum CEA concentration, number and size of
      liver metastases were prognostic factors. The patients were classified into high
      risk, moderate risk, and low risk groups according to the PI value, and there was
      significant difference in survival rates between each two groups. CONCLUSIONS:
      Liver metastasis resection, serum CEA concentration, number and size of liver
      metastases are important prognostic factors for liver metastases from colorectal
      cancer. In order to improve the survival rate, liver metastases should be
      resected for suitable patients. Moreover, PI value could be used to predict the
      prognosis of patients with liver metastases from colorectal cancer.

PMID- 16965661
TI  - [Prognostic analysis of 220 colorectal cancer patients with synchronous liver
      metastases].
AB  - BACKGROUND & OBJECTIVE: Colorectal cancer is one of the most common malignant
      tumors in China. Synchronous liver metastases occur in 10%-25% colorectal cancer
      patients. This study was to elucidate the prognostic factors and treatment
      choices for colorectal cancer patients with synchronous liver metastases.
      METHODS: Records of 220 colorectal cancer patients with synchronous liver
      metastases initially treated at Cancer Center of Sun Yat-sen University from Dec.
      1995 to Dec. 2002 were reviewed. Prognostic factors were analyzed by Kaplan-Meier
      method and Cox regression model with SPSS12.0 software. RESULTS: The 5-year
      overall survival rate was 5.52%, the median survival time of the patients was
      12.93 months. Univariate analysis of clinical characteristics revealed that the
      number, size and distribution of liver metastases, extrahepatic disease, serum
      CEA level at diagnosis, N status, and histology were prognostic factors.
      Univariate analysis of clinical treatment factors showed that treatment modality,
      primary site resection, and chemotherapy regimen were prognostic factors.
      Multivariate analysis showed that the number and size of liver metastases,
      extrahepatic disease, serum CEA value at diagnosis, treatment modality, primary
      tumor resection, and chemotherapy regimen were independent prognostic factors of
      colorectal cancer patients with synchronous liver metastases. CONCLUSIONS: Liver
      metastases larger than 5 cm in diameter, bilobar liver metastases, extrahepatic
      invasion or metastases, and CEA level more than 200 microg/L at diagnosis are
      adverse prognostic factors. Primary tumor resection and liver resection should be
      considered for all suitable patients with colorectal metastases to the liver
      alone. Liver-target intervention and/or systemic chemotherapy might be a good
      choice for inoperable patients. If possible, systemic chemotherapy containing
      oxaliplatin is preferred.

PMID- 16965662
TI  - [Prognostic analysis of 384 male patients with rectal cancer].
AB  - BACKGROUND & OBJECTIVE: The incidence of colorectal cancer is increasing in
      China, of which rectal cancer accounts for over 50%. Because of the limitation of
      pelvic cavity, the selection of surgical procedures, the proportion of sphincter
      saving and prognosis of male patients are different from those of female
      patients. This study was to analyze the correlations of clinicopathologic
      features of rectal cancer in 384 male patients to their prognosis. METHODS:
      Correlations of 12 clinicopathologic factors of 384 male patients with rectal
      cancer to the prognosis were studied with univariate and multivariate analysis.
      RESULTS: Univariate analysis revealed that tumor site, gross type, histologic
      type, infiltrative extent to bowel wall, site of lymphatic metastasis and Dukes'
      stage were prognostic factors of male patients with rectal cancer. Multivariate
      analysis revealed that histologic type and site of lymphatic metastasis were
      independent prognostic factors. CONCLUSION: Histologic type and site of lymphatic
      metastasis are independent prognostic factors of male patients with rectal
      cancer.

PMID- 16965663
TI  - [Correlation of growth hormone receptor expression to preoperative
      radiosensitivity of rectal cancer patients].
AB  - BACKGROUND & OBJECTIVE: Growth hormone (GH) could activate pathways involved in
      DNA repair process by binding to growth hormone receptor (GHR), which is thought
      as one of the mechanisms of radioprotection. This study was to evaluate the
      correlation of GHR expression to radiosensitivity of rectal cancer. METHODS: The
      expression of GHR in biopsy specimens from 98 rectal cancer patients before
      preoperative irradiation and postoperative specimens was detected by
      immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction
      (RT-PCR). Radiosensitivity was evaluated according to Rectal Cancer Regression
      Grading. RESULTS: IHC revealed that GHR overexpression was positively correlated
      to poor response to radiotherapy (P<0.001, rs=0.399); RT-PCR also showed that
      radiosensitivity was significantly higher in GHR mRNA-negative group than in GHR
      mRNA-positive group (P<0.001, rs=0.398). Compared with the biopsy specimens
      before preoperative irradiation, the paired postoperative specimens showed
      significantly increased GHR expression in residual cancer cells (P<0.001).
      CONCLUSION: Detection of GHR expression before preoperative irradiation may
      predict radiosensitivity of rectal cancer.

PMID- 16965664
TI  - [Correlations of biomolecular markers, such as P53 protein and vascular
      endothelial growth factor, to radiosensitivity of nasopharyngeal carcinoma].
AB  - BACKGROUND & OBJECTIVE: About 20%-40% nasopharyngeal carcinoma (NPC) patients,
      who are in the same staging group, receiving the same treatment modality and
      radiotherapy dose, relapse in the irradiated fields within 5 years. This is
      mainly due to the differences in internal radiosensitivity. This study was to
      analyze the proliferation, apoptosis, angiogenesis, and lymphogenesis of tumor
      cells, and to explore the correlation of these factors to radiosensitivity.
      METHODS: P53 protein, vascular endothelial growth factor (VEGF) protein, survivin
      protein, VEGF-C protein, Ki67 protein, and microvascular density (MVD) of 60
      biopsy samples from radiosensitive group and 60 from radio-resistant group were
      detected by immunohistochemistry, respectively. Their correlations to clinical
      characteristics were analyzed. RESULTS: The positive rates of P53, VEGF,
      survivin, VEGF-C, Ki67 were 65.0%, 57.5%, 60.8%, 42.5%, 57.5%, respectively. The
      positive rates of P53 and VEGF, and MVD in the radio-sensitive group and in the
      radio-resistant group were (25.97+/-21.26)%, (18.50+/-19.86)%, 32.65+/-19.61 and
      (37.85+/-28.67)%, (30.83+/-23.94)%, 41.95+/-16.97, respectively (P<0.05). The
      positive rates of Survivin, VEGF-C, and Ki67 between the two groups had no
      statistic difference (P>0.05). The correlations between P53, VEGF, and MVD were
      obvious. CONCLUSION: P53 protein, VEGF protein and MVD might be biomolecular
      markers for evaluating the internal radiosensitivity of NPC patients.

PMID- 16965666
TI  - [MRI performance and diagnosis of schwannomas from cranial nerves in posterior
      cranial fossae].
AB  - BACKGROUND & OBJECTIVE: Cranial nerve schwannomas originate frequently in
      posterior cranial fossae and have various and complex MRI performances, some of
      which are still not well known. This study was to explore MRI performances and
      features of schwannomas from cranial nerves in posterior cranial fossae. METHODS:
      The MRI performances of 75 cases of schwannoma from cranial nerves in posterior
      cranial fossae, including trigeminal (n=9), facial (n=1), acoustic (n=53), 9th
      11th (n=9) and hypoglossal (n=3) schwannomas, confirmed by surgical and
      pathologic findings, were analyzed retrospectively. RESULTS: Most of schwannomas
      in posterior cranial fossae were solid-cystic lesions when their sizes were
      larger than 1.5 cm in diameter. Small lesions (less than 1.5 cm in diameter) may
      be completely solid, which were closely related to cranial nerves. On T1WI, the
      solid part of tumor appeared iso- or slightly hypointense, while cystic part was
      hypointense. On T2WI, solid part appeared high or slightly high signal intensity,
      but cystic part appeared very high signal intensity. On contrast-enhanced T1WI,
      there was obvious enhancement in the solid part, but not in the cystic part. Some
      typical signs were very useful to infer tumor origin, such as, dumbbell-shaped
      trigeminal schwannoma extended across the middle and posterior cranial fossa,
      enlargement of internal auditory canal, widened jugular foramen and hypoglossal
      foramen caused by acoustic schwannoma, the 9th-11th shcwannoma, and hypoglossal
      schwannoma, respectively. The correct ratio for qualitative diagnosis of
      schwannoma was 92% using MRI, but the incorrect ratio for identifying the nerve
      of tumor origin was 8.7%. CONCLUSION: MRI is a good method in qualitative
      diagnosis of schwannoma and identifying cranial nerves of tumor origin in
      posterior cranial fossae.

PMID- 16965665
TI  - [Prognostic analysis of 62 cases of nasal NK/T-cell lymphoma].
AB  - BACKGROUND & OBJECTIVE: Extranodal NK/T-cell lymphoma of nasal type (ENKTL) is a
      rare disease entity with unique biological behavior, of which definitive
      characteristics are still unknown. This study was to investigate the clinical
      features and prognostic factors of ENKTL in the population of southern China.
      METHODS: Records of 62 patients with pathologically confirmed ENKTL, treated in
      Cancer Center of Sun Yat-sen University from Jan. 1999 to Dec. 2004, were
      reviewed. Detailed clinical and laboratory data were included in univariate
      analysis, and statistically significant factors in univariate analysis were then
      included in multivariate analysis. RESULTS: Of the 62 patients, 47 were men, and
      15 were women, with the median age of 42; 92% of the patients had localized
      disease, and 76% had international prognostic index (IPI) of 0 or 1. Before
      treatment, 26% of the patients had anemia, 92% had ECOG performance status (PS)
      score of 0-1, and 53% presented B symptoms. With a median follow-up duration of
      18 months, the median overall survival time was 27 months (95% CI: 10-45 months).
      In multivariate analysis, hemoglobin (Hb) <110 g/L, B symptoms, and ECOG PS score
      >1 were statistically significant unfavorable prognostic factors. CONCLUSION: Hb
      together with B symptoms and PS score may be independent prognostic factors for
      ENKTL.

PMID- 16965667
TI  - [Effects of gantry position on the accuracy of lead block localization and
      relative quality control methods].
AB  - BACKGROUND & OBJECTIVE: To date, the low-melting point lead blocks are commonly
      used as a beam modifier for the accurate three-dimensional (3D) radiotherapy in
      China. However, care should be taken when using blocks even though they are
      verified on the specified simulator or linear accelerator before treatment. This
      is because that those verifications are only performed under the gantry angle of
      0 degree. For the oblique gantry angles, the block may shift in the tray leading
      to the positioning error. In this study, we explored the influence of gantry
      position on the accuracy of lead block localization, and the relative quality
      control methods were also provided. METHODS: After rotating the gantry to 90
      degrees and setting the collimator angle to 0 degree on a Siemens linear
      accelerator, a crosshair was marked on the plastic base of the lead block fitted
      to the tray according to the crosshair of light field of the linear accelerator.
      Then the discrepancy between the base crosshair and the light crosshair was
      investigated for different gantry positions and collimator angles. RESULTS: There
      was clearance between the plastic base of the lead block and the block tray. As
      for some collimator angles at oblique gantry positions, the lead block shifted in
      the tray due to the gravity. This led to the position error of blocked radiation
      fields from 0 up to 3.6 mm at the isocenter plane. CONCLUSIONS: Accurately
      marking the crosshair on the plastic base of the lead block is an effective
      method of correctly fixing the lead block influenced by the plastic base as well
      as of double checking the accuracy of the localization of the lead block. The
      positioning error of oblique gantry positions can be minimized by limiting the
      collimator to some degrees which makes the block tray opening to the ceiling or
      parallel to the ground while the bisector of the restrictive angle points
      slanting to the ceiling (that is, the first baseline of the block tray points
      inclined or right to the ceiling).

PMID- 16965668
TI  - [Cell brain abnormalities in carcinogenesis].
AB  - Cancer seriously threatens the health of humans. The mechanism underlying the
      carcinogenesis, however, is unclear. Among all the related hypotheses, the lately
      postulated 'cell brain' theory, challenging the conventional theory that gene
      abnormalities are the major players in carcinogenesis, is catching more and more
      attentions. According to this theory, the complex composes of the centrosome,
      centrioles, and connecting microtubules, and acts as the commandeering center of
      a cell in the structures and functions, equals to the brains of human being and
      animals, centering all the cellular activities. As far as carcinogenesis is
      concerned, cancer was interpreted by this theory as a brain illness' rather than
      a genetic disease. This article, based on the latest findings, reevaluated the
      roles of the composing parts of cell brain, discussed their correlations to
      cancer development, and further explored the mechanisms of carcinogenesis
      including hepatocarcinogenesis. It will contribute not only to improving cancer
      diagnosis and prevention but also to the design of novel anticancer agents,
      particularly the centrosome/cell brain-targeting agents.

PMID- 16965669
TI  - [Abscopal effect on metastatic tumor induced by oncolytic virus of H101 combining
      with local heating].
AB  - BACKGROUND & OBJECTIVE: The abscopal effect on the tumors is a distant antitumor
      activity induced by local treatments. The study was to observe the induction of
      abscopal effect by the combination of H101 oncolytic virotherapy with local
      heating. METHODS: Five patients with histologically confirmed, surgically
      unresectable metastatic malignant tumors (2 nasopharyngeal carcinomas, 1
      pulmonary carcinoma, 1 parosteal sarcoma and 1 bladder carcinoma) that had
      definitely failed to the conventional chemotherapy and radiotherapy or refused
      these therapies were enrolled in this experimental therapy. All patients were
      treated with local intra tumor injection of H101 (5x10(11) - 15x10(11) VP)
      combined with 60-min heating at 42 degrees C. RESULTS: Two patients were cured
      with complete regressions of both injected and non-injected tumors and have
      survived for a long period up to date. Three patients responded to the novel
      therapy variously and eventually died from the disease, who survived 29, 15 and
      13 months, respectively. CONCLUSION: The abscopal antitumor effect could be
      induced by the combination of H101 local intratumoral injection with heating.

PMID- 16965670
TI  - Effects of p73 gene overexpression on apoptosis and chemosensitivity of human
      lung adenocarcinoma cell line A549.
AB  - BACKGROUND & OBJECTIVE: It is important to overcome gene therapy resistance
      caused by wt-p53 in non-small cell lung cancer (NSCLC) . The p53 family member
      p73 is a p53 homolog. This study was to observe the apoptosis and
      chemosensitivity effect of p53-resistant human lung adenocarcinoma cell line A549
      following wild-type p73 gene transfection alone or combined with chemotherapeutic
      agents. METHODS: Plasmids pcDNA3-HA-p53 or pcDNA3-HA-p73alpha were transfected
      into A549 cells with Dosper. Positive cell clones were selected using G418. The
      exogenous p53 or p73alpha gene expressions were examined by Western blot. MTT
      assay was used to analyze the response of transfected cells to cisplatin (DDP) or
      adriamycin (ADM). The drug-induced apoptosis of transfected cells was measured by
      flow cytometry, TUNEL technique and DNA fragmentation. The biological behavior
      change of transfected cells was investigated by colony formation assay. RESULTS:
      Transfected A549 cells stably overexpressed p53 or p73alpha. Low concentration of
      chemotherapeutic agents (6.25 micromol/L DDP or 0.25 micromol/L ADM) which had no
      obvious effects on non-transfected cells, suppressed p73-transfected cell growth
      significantly; the 50% inhibitory concentration (IC(50)) of DDP for A549 cells
      decreased from 22.65 micromol/L to 3.75 micromol/L, and the IC(50) of ADM
      decreased from 4.20 micromol/L to 0.06 micromol/L after p73alpha transfection.
      p73, but not p53, sensitized A549 cells to DDP and ADM: DDP-induced apoptosis
      rate was increased from 10.6% to 36.8% (P<0.01), ADM-induced apoptosis rate was
      increased from 13.0% to 41.1% (P<0.01) after p73 transfection. DDP and ADM
      significantly suppressed colony formation of p73-transfected cells compared with
      parental cells (P<0.01). The sensitive enhancement ratios for DDP and ADM were
      2.0 and 2.4, respectively. CONCLUSIONS: Exogenous p73 gene enhances the
      sensitivity of A549 cells to chemotherapeutic agents by inducing apoptosis
      through p53-independent pathway. p73 gene could be used to treat p53-resistant
      tumors.

PMID- 16965671
TI  - [Study on apoptosis of oral squamous carcinoma cell line KB and KBv200 induced by
      survivin RNAi].
AB  - BACKGROUND & OBJECTIVE: Survivin, a member of IAPs (inhibition of apoptosis
      proteins) family, has been revealed by many studies to inhibit the activation of
      caspase-3, caspase-7 and caspase-9, and thus increase the anti-apoptotic effect
      of cancer cells, which subsequently makes the cells to become resistant to
      chemotherapy in cancer treatment. Survivin is expressed in human oral squamous
      carcinoma cell line KB and its multiple-drug resistant (MDR) cell line KBv200.
      This study was to compare the apoptosis induced by silencing survivin gene
      between these two squamous cell lines. METHODS: Mu6/survivin plasmid which
      expressed shRNA against survivin was transfected into both KB and KBv200 cells to
      inhibit the expression of survivin gene. Survivin mRNA and protein expression was
      detected by semi-quantitative RT-PCR and flow cytometry (FCM), respectively. Cell
      apoptotic rate was measured by flow cytometry after PI staining, and apoptotic
      morphology of cells was observed under a fluorescent microscope after
      Hoechst33258 staining. Activation of caspase-3 was measured by colorimetric
      assay. MTT was used to evaluate the growth inhibition of tumor cells. RESULTS:
      Expression of survivin, which was higher in KBv200 at mRNA and protein level, was
      detected in both KB and KBv200. After 48 h transfection with mu6/survivin
      plasmid, the expression level of survivin mRNA in KB and KBv200 was reduced by
      (61.98+/-8.12)% and (59.29+/-6.32)%; and that of survivin protein was decreased
      by (44.25+/-5.26)% and (38.76+/-4.31)% compared with the control group. Moreover,
      KB and KBv200 cells exhibited typical apoptotic cell morphology by Hoechst 33258
      staining. Apoptosis, which was higher in KB cells, was increased significantly at
      24, 48, 72 h after the transfection of mu6/surviving in KB and KBv200 cells, and
      reached the peak at 48 h. Similarly, activation of caspase-3 was elevated
      significantly, and reached the peak at 48 h. MTT assay revealed the inhibitory
      rates were (33.04+/-2.16)%, (56.25+/-3.32)% and (58.26+/-5.14)% in KB cells, and
      (35.23+/-3.42)%, (44.90+/-4.12)% and (44.19+/-4.37)% in KBv200 cells at 24, 48,
      72 h after the transfection, respectively. Growth rate was lower in KB cells at
      48, 72 h after the transfection compared with KBv200 cells. CONCLUSION: RNA
      interference could silence the expression of survivin, which significantly
      induces apoptosis not only in KB cells, but also in drug resistant KBv200 cells.

PMID- 16965672
TI  - [Nanoliposomal quercetin inhibits formation of malignant ascites of
      hepatocellular carcinoma].
AB  - BACKGROUND & OBJECTIVE: Quercetin is a potential chemotherapeutic drug with many
      biological activities. However, the insolubility of quercetin seriously limits
      its clinical use. This study was to investigate the biodistribution of quercetin
      encapsulated by pegylated nanoliposomes and its therapeutic efficacy on the
      formation of carcinomatous ascites of hepatocellular carcinoma in mice. METHODS:
      Nanoliposomal quercetin was prepared with conventional rotary evaporation method.
      BALB/c mice inoculated with hepatocellular carcinoma cells (H22) at the anterior
      right subaxilla for twelve days were given intravascular injection with
      nanoliposomal quercetin at 1.5 mg/body (based on quercetin) at different time
      points. Then the levels of quercetin in the plasma, tumor tissues and normal
      organs were tested by high pressure liquid chromatography (HPLC). Various dosages
      of nanoliposomal quercetin were peritoneally given to tumor-bearing mice to
      determine the optimal dose. The tumor-bearing mice were treated intraperitoneally
      with 100 mg/kg nanoliposomal quercetin once a day for 14 days. The formation of
      malignant ascites, increase of body weight, survival time and peritoneal
      capillary permeability were assessed. Apoptotic cells in ascites were detected by
      flow cytometry. RESULTS: Nanoliposomal quercetin was a spherical particle with
      25% drug content (W/W) and 130+/-20 nm in diameter. Nanoliposomal quercetin
      effectively aggregated in tumor tissues and its half-life period was 4 h.
      Nanoliposome quercetin inhibited the formation of malignant ascites of
      hepatocellular carcinoma model in a dose-dependent manner. Moreover, 100 mg/kg
      nanoliposomal quercetin significantly enhanced the apoptosis of cancer cells in
      ascites, inhibited the increase of body weight, reduced peritoneal capillary
      permeability and prolonged the survival time of tumor-bearing mice compared with
      PBS control. CONCLUSION: Nanoliposomal quercetin can effectively accumulate in
      tumor tissues and inhibit the formation of malignant ascites, thus it might be
      used as a potential antitumor drug which deserves future study.

PMID- 16965673
TI  - [Mechanism of apoptosis induced by trichostatin A in leukemia Molt-4 cells
      analyzed by microarray].
AB  - BACKGROUND & OBJECTIVE: Histone deacetylase is overexpressed in a variety of
      cancers and is closely correlated with oncogenic factors. A histone-deacetylase
      inhibitor, trichostatin A (TSA), has been shown to induce apoptosis in many
      cancer cells at submicromolar concentrations. However, the mechanism remains
      unknown. This study was to investigate the underlying mechanism of trichostatin A
      on apoptosis of Molt-4 cells by characterizing the global gene expression
      profiles before and after TSA treatment. METHODS: PI single-labeled flow
      cytometry, MTT and DNA ladder were used to observe the effect of TSA on apoptosis
      of MOLT-4 cells and normal human peripheral blood mononuclear cells (PBMC).
      Microarray and reverse transcription-polymerase chain reaction (RT-PCR) and
      Western blot were used to detect the differentially expressed genes of Molt-4
      cells after incubation with TSA. RESULTS: TSA could induce apoptosis in Molt-4
      cells in a dose and time-dependent manner. Besides, the dose of TSA within the
      time duration which could induce significant apoptosis in Molt-4 cells did not
      demonstrate apparent cytotoxicity to PBMCs. After incubation with TSA for 9
      hours, 313 genes were detected down-regulated by microarray. Proteins encoded by
      these genes included signal transduction molecules, transcription factors,
      enzymes etc., which were involved in the regulation of cell growth,
      differentiation and survival. STAT5A, MYC and ikaros were down-regulated by
      80.4%, 77.3% and 83.1%, respectively. The changes of the three genes were
      confirmed by RT-PCR and the changes of STAT5A and MYC were further confirmed by
      Western blot. CONCLUSION: The inhibition of cell growth and induction of
      apoptosis by TSA in Molt-4 cells may be due to the changes of pro-proliferation
      genes and anti-apoptosis genes.

PMID- 16965674
TI  - [Reversal of multidrug resistance of human hepatocellular carcinoma cells by wild
      type p53 gene and related mechanisms].
AB  - BACKGROUND & OBJECTIVE: The mechanism of cell apoptosis plays an important role
      in tumor multidrug resistance (MDR). Wild-type p53 (wt-p53) gene is an activator
      of cell apoptosis, and is closely related to tumor MDR. This study was to explore
      the effect of p53 gene on the reversal of MDR of human hepatocellular carcinoma
      (HCC) and related mechanisms. METHODS: The eukaryotic expression plasmid pCR 3.1
      p53 was constructed and transfected into human HCC cell line Bel-7402.
      Proliferation and chemosensitivity of Bel-7402 cells to vincristine (VCR) were
      measured by MTT assay. The morphology of transfected Bel-7402 cells was observed.
      The expression of P-glycoprotein (P-gp) was detected by immunochemistry. The
      expression of multidrug resistance gene 1 (mdr1), multidrug resistance related
      protein (MRP), glutathione S-transferase pi (GST pi), and topoisomerase II alpha
      (Topo II alpha) were detected by reverse transcription-polymerase chain reaction
      (RT-PCR). RESULTS: The growth of wt-p53-transfected Bel-7402 cells was obviously
      slower than that of untransfected cells. After transfection with wt-p53, the
      chemosensivity of Bel-7402 cells to VCR was enhanced at the concentration of
      0.01, 0.1, 1.0, 10, and 25 microg/ml. The optimal concentration was 1.0
      microg/ml. After wt-p53 transfection and VCR treatment, the number of Bel-7402
      cells was decreased; the cells were swollen severely with irregular projections;
      pyknosis, karyorrhexis and karyolysis were observed. After wt-p53 transfection,
      the expression of mdr1 and P-gp in Bel-7402 cells was down-regulated remarkably,
      and the expression of Topo II alpha was up-regulated. CONCLUSION: Wild-type p53
      gene raises chemosensitivity of Bel-7402 cells to VCR, which may be partly
      related to the down-regulation of mdr1 and up-regulation of Topo II alpha.

PMID- 16965675
TI  - [Troglitazone sensitizes effect of epirubicin on breast cancer cells].
AB  - BACKGROUND & OBJECTIVE: Peroxisome proliferator-activated receptor gamma
      (PPARgamma) is known to be highly expressed in breast cancer tissues.
      Thiazolidinediones (TZD), the specific ligands for PPARgamma, can inhibit cell
      proliferation and induce apoptosis. This study was to investigate the possibility
      of using troglitazone, one of TZD, as the sensitizer of epirubicin in the
      treatment of estrogen receptor (ER) negative breast cancer. METHODS: MTT assay
      and flow cytometry were used to examine the cell proliferation and apoptosis in
      two ER negative breast cancer cell line MDA-MB-435S and MDA-MB-231. Cells were
      treated with either troglitazone or epirubicin alone or co-treated with
      troglitazone and epirubicin. Western blot analysis was used to assess the
      expression level of Bcl-2. The migration potential of cells with different
      treatments was analyzed by the wound healing assay. RESULTS: The effect of
      epirubicin on inhibiting cell proliferation of breast cancer cells was enhanced
      by co-treatment with troglitazone in the range of 4 micromol/L to 24 micromol/L.
      The 50% inhibitory concentration (IC(50)) of epirubicin was reduced to 60% when
      combined with troglitazone compared to the treatment with epirubicin only.
      Treatment of cells with troglitazone or epirubicin alone could not induce
      significant apoptosis. However, the apoptotic indexes of MDA-MB-435S and MDA-MB
      231 cells co-treated with troglitazone and epirubicin were (5.48+/-0.45)% and
      (10.08+/-1.89)%, respectively. Co-treatment with troglitazone and epirubicin
      further downregulated the expression level of Bcl-2 and inhibited cell migration
      simultaneously. CONCLUSIONS: Troglitazone could not only augment the effect of
      epirubicin on inhibiting cell proliferation and inducing apoptosis, but also
      suppress the migration of breast cancer cells. Troglitazone may sensitize the
      effect of epirubicin on breast cancer cells.

PMID- 16965676
TI  - [Inhibitory effect of carbamazepine on proliferation of estrogen-dependent breast
      cancer cells].
AB  - BACKGROUND & OBJECTIVE: Carbamazepine, which has been used as an anti-epileptic
      drug in clinic for many years, is currently recognized as a histone deacetylase
      inhibitor (HDI), most of which showed anti-tumor characteristics. This study was
      to investigate the inhibitory effect of carbamazepine on estrogen dependent
      breast cancer cell lines with estrogen receptor alpha (ERalpha) expression and
      further explore the underlying mechanisms. METHODS: Sulforhodamine B viability
      assay was used to evaluate the viability of various cells treated with different
      drugs. Western blot and reverse transcription-polymerase chain reaction (RT-PCR)
      were performed to detect the protein and mRNA expression of ERalpha and Cyclin
      D1. Immunofluorescence assay was employed to observe HER-2 expression in MCF-7RT
      cells, which were resistant to tamoxifen. Immunoprecipitation was performed to
      detect the chaperon function and acetylation level of Hsp90. RESULTS:
      Carbamazepine treatment could inhibit the proliferation of MCF-7 and T47D cells
      stimulated by estradiol (P<0.01). Carbamazepine and 4-hydroxytamoxifen (4-OHT)
      demonstrated a synergic effect on the inhibition of proliferation of MCF-7 cells
      stimulated by estradiol (q=1.00). Cabamazepine reversed the proliferation of MCF
      7RT cells stimulated by 4-hydroxytamoxifen (P<0.01). Carbamazepine treatment
      could decrease the expression of ERalpha and Cyclin D1 at protein and mRNA level
      in ERalpha-positive cells and could reduce HER-2 expression in MCF-7RT cells. The
      decrease of ERalpha and Cyclin D1 expression was inhibited by MG132, an inhibitor
      of 26S proteosome. Carbamazepine treatment elevated the acetylation level of
      Hsp90 and disrupted its chaperon function. CONCLUSIONS: Carbamazepine shows
      significant anti-proliferation effect in ERalpha-positive breast cancer cell
      lines and this might be due to the enhancement of proteosome-mediated degradation
      of ERalpha and Cyclin D1 by carbamazepine. Furthermore, carbamazepine could
      reverse HER-2 dependent drug resistance to 4-OHT by reducing HER-2 expression.

PMID- 16965677
TI  - [Effects of hyperthermic chemotherapy on gastrointestinal cancer cells in vitro].
AB  - BACKGROUND & OBJECTIVE: Little evidence is known from experimental research for
      intraoperative hyperthermic intraperitoneal chemotherapy. This study was to
      investigate the effect of hyperthermic chemotherapy on gastrointestinal cancer
      cells in vitro and explore the possible factors which may affect this method.
      METHODS: Gastric cancer cell line MGC-803 and intestinal cancer cell line HCT-116
      were chosen. Cells were treated with different drugs, temperatures and duration.
      Cell viability and growth were measured by MTS-PMS assay. The morphology of the
      cells was observed under a microscope. RESULTS: Significant synergistic effect
      was observed when the two cancer cell lines were treated with 5-FU, MMC, DDP and
      THP in combination with elevated hyperthermia from 41 degrees C to 45 degrees C
      compared with control group (P<0.01). The strongest effect was achieved at 45
      degrees C, which the inhibitory effects of these four drugs were 61.7%, 79.2%,
      88.7%, 94.7% on MGC-803 and 76.4%, 78.7%, 77.8%, 91.7 on HCT-1116, respectively.
      The inhibitory effect demonstrated a time and dose-dependent manner in HCT-116
      cells within a certain period of time. The effect revealed a flat curve after 90
      min when HCT-116 was treated with 43 centigrade. THP had the strongest effect at
      any conditions among all tested drugs (P<0.01). Either simple thermotherapy or
      chemohyperthermia displayed considerable killing effects on cancer cells which
      were confirmed by microscope observation. And a great deal of dead cells were
      observed when treated with chemohyperthermia. CONCLUSIONS: DDP or MMC reveals
      relatively satisfactory antitumor effects with the optimal temperature of 43-45
      degrees C. Taken practical application into consideration, 60 min may be selected
      in clinical use. Synergistic antitumor effects of THP in combination with
      hyperthermia were prior to 5-FU, DDP or MMC, which deserve further clinical
      research.

PMID- 16965678
TI  - [Correlation of antitumor drug sensitivity between marrow mesenchymal stem cells
      (MSCs) and hepatocarcinoma cells in rats].
AB  - BACKGROUND & OBJECTIVE: As hepatocarcinoma stem cells may originate from oval
      cells and oval cells are difficult to be separated and purified, MSCs (marrow
      mesenchymal stem cells), which are the progenitor cells of the hepatocarcinoma
      stem cells, were selected instead in our study to investigate the correlation of
      anticancer drug sensitivity between hepatocarcinoma cells and MSCs in rats.
      METHODS: The primary liver carcinoma modle of rats was induced by
      diethylnitrosamine. Tumor cells and MSCs from eight hepatocarcinoma rats were
      separated. The inhibitory effects of 3 anticancer drugs [adriacin (0.04
      microg/ml), cisplatin (0.2 microg/ml) and fluorouracil (1 microg/ml)] to
      hepatocarcinoma cells and MSCs were measured by MTT assay. The weight of the
      tumor in nude mice which were injected with rat hepatocarcinoma cells was
      measured after 6 weeks. Then the correlation of the inhibitory ratio of 3
      anticancer drugs to hepatocarcinoma cells and MSCs, and to the tumor weight of
      nude mice was analyzed. RESULTS: No correlation was revealed between the
      inhibitory ratio of 3 anticancer drugs to hepatocarcinoma cells and the tumor
      weights of nude mice injectal with drug treated tumor cells. The correlation
      coefficient was: 0.6307 (adriacin, P>0.05), 0.4358 (fuiorouracil, P>0.05) and
      0.7080 (cisplatin, P>0.05). No correlation was observed between the inhibitory
      ratio of 3 anticancer drugs to hepatocarcinoma cells and to MSCs. The correlation
      coefficient was: 0.6316 (adriacin, P>0.05), 0.4214 (fluorouracil, P>0.05) and
      0.5943 (cisplatin, P>0.05). However, significant reverse correlation was found
      between the inhibitory ratio of 3 anticancer drugs to MSCs and the tumor weights
      of nude mice injectal with drug treated tumor cells. The correlation coefficient
      was: -0.8308 (adriacin, P<0.05), -0.8991 (fluorouracil, P<0.01) and -0.8311
      (cisplatin, P<0.05). CONCLUSIONS: Conventional anticancer drug sensitivity
      experiments could not reflect the chemoresistance of the hepatocarcinoma cells.
      However the inhibitory ratio of the anticancer drugs to MSCs in the
      hepatocarcinoma rats can reflect the chemoresistance of hepatocarcinoma cells
      accordingly.

PMID- 16965679
TI  - [Experimental study on antitumor effects of Shen Qi Jin Kang (SQJK)].
AB  - BACKGROUND & OBJECTIVE: SHEN QI JIN KANG (SQJK) capsule is a complex preparation,
      consisting of effective components extracted from radix astragali, ginseng,
      curcuma, etc. It has been demonstrated to be able to decrease tumor volume,
      increase life quality and prolong survival time in clinic application. The study
      was to investigate the antitumor effects of SQJK capsule in vivo and in vitro,
      and further explore the possible mechanisms. METHODS: The proliferation of cancer
      cells treated with SQJK was measured by MTT assay in twelve cell lines; cell
      apoptosis was observed under an electric microscopic and detected by flow
      cytometry in MCF-7 and MA891 cells; altered telomerase activity in A549 cells was
      examined by a telomerase activity detection kit. Furthermore, the inhibitory
      effect of SQJK on tumors was also surveyed in vivo by using mice and nude mice
      models bearing transplanted tumors. RESULTS: Inhibitory concentration 50%
      (IC(50)) of SQJK on A549, U251, MCF-7, Ketr-3, EJ, and A2780 cells was 30.954
      microg/ml, 31.746 microg/ml, 37.220 microg/ml, 40.366 microg/ml, 41.398
      microg/ml, and 45.083 microg/ml, respectively. Typical sub-G1 peaks, indicating
      the occurrence of apoptosis, were revealed in MA891and MCF-7 cells treated with
      SQJK. Morphological changes including cell shrinkage and condensation of
      chromosomes were observed. The telomerase activity of A549 was inhibited after 48
      h of SQJK treatment. SQJK 1.8 g/kg inhibited the weights of transplanted tumors
      (MA891, H22, S180 in mice and PC-3 (M), MCF-7 and Ketr-3 in nude mice) by 50.84%,
      48.91%, 40.88%, 62.50%, 47.83% and 30.06%, while SQJK 3.6 g/kg inhibited the
      weights by 56.49%, 59.62%, 55.70%, 70.76%, 58.66% and 50.18%, respectively.
      CONCLUSION: SQJK has demonstrated antitumor bioactivity both in vitro and in
      vivo, which may be related to its effects of inducing apoptosis and decreasing
      telomerase activity.

PMID- 16965680
TI  - [A randomized comparative trial of three combined regimens containing cisplatin
      for treatment of advanced non-small cell lung cancer].
AB  - BACKGROUND & OBJECTIVE: Vinorelbine (NVB), paclitaxel (TAX), and gemcitabine
      (GEM) are first-line chemotherapeutic drugs in the treatment for non-small cell
      lung cancer (NSCLC) currently. There are many domestically retrospective studies
      to compare efficacies and adverse reactions among these three regimens, all of
      which has composed of cisplatin (DDP). This randomized study was to investigate
      the efficacies and toxicities of these three regimens in NSCLC treatment, in
      order to choose a feasible regimen for NSCLC patients. METHODS: A total of 276
      NSCLC patients were randomly assigned to a regimen of NP (NVB plus DDP ), or TP
      (TAX plus DDP), or GP (GEM plus DDP). Efficacies and toxicities were analyzed and
      compared after two cycles. RESULTS: The response rates were 42.3% (41/97) in NP
      arm, 43.0% (40/93) in TP arm, and 43.4% (36/83) in GP arm, and complete remission
      rates were 1.0% (1/97), 2.2% (1/93) and (0/83) respectively, without significant
      difference. The median survival time, disease-free survival time and 1-year
      survival rate were 8.5 months, 4.1 months and 31.9%; 8.8 months, 3.8 months and
      33.3%, and 9.2 months, 3.9 months, 31.3%, respectively in NP, TP and GP arms
      without significant difference. The major adverse reactions were stage 3 to 4
      myelo-suppression, nausea/vomiting, fatigue and phlebitis. There were highest
      incidences of leucopenia (42.2%), neutropenia (36.2%) and lowest incidence of
      thrombocytopenia (53.0%) in GP arm compared to NP arm (77.8%, 67.7%, 12.1%) or TP
      arm (71.0%, 57.0%, 13.0%) statistically (P<0.01 for all). The rates of
      nausea/vomiting in GP arm (16.8%) and TP arm (25.8%) were significantly lower
      than in NP arm (41.4%)(P<0.05); and the rate of fatigue in GP arm (38.5%) or
      phlebitis in NP arm was most frequent among the three arms (P=0.000, 0.008
      respectively). CONCLUSIONS: There is no significant difference in short-term
      efficacy of chemotherapy regimen NP, TP and GP. TP and GP regimens, both of which
      possesses its own advantage, are more tolerable than NP regimen which has the
      most side effects.

PMID- 16965681
TI  - [Phase II trial of prolonged infusion of low-dose gemcitabine in advanced non
      small cell lung cancer treatment].
AB  - BACKGROUND & OBJECTIVE: Gemcitabine combined with cisplatin has been taken as the
      front-line regimen for patients with advanced non-small-cell lung cancer (NSCLC).
      The routine use of gemcitabine is intravenous injection of a dose of 1,000
      mg/m(2) within 30 minutes on days 1 and 8, and the treatment is repeated every 3
      weeks. This study was to evaluate the efficacy and safety of 6-hour continuous
      infusion of low dose of gemcitabine plus cisplatin for patients with advanced
      NSCLC. METHODS: Forty-eight patients with measurable stage III B/IV NSCLC and
      without chemotherapy were enrolled. All of them received 6-hour continuous
      infusion of gemcitabine 250 mg/m(2) on day 1 and 8 plus cisplatin 75 mg/m(2) on
      day 2-4 for more than 2 cycles. The cycle was repeated every 3 weeks. RESULTS:
      All 48 patients were evaluated for toxicity and 46 for response. The overall
      response rate was 32.5% (completed and partial response rates were 2.2% and
      30.3%, respectively). The median time to progression was 5.1 months, median
      survival time was 10.2 months; and 1-year survival rate was 36.6%. The main
      hematologic toxicity consisted of 60.4% neutropenia, 39.5% thrombocytopenia.
      Grade III-IV neutropenia and thrombocytopenia were 20.8% and 12.5%, respectively.
      CONCLUSION: Six-hour prolonged infusion of low dose gemcitabine combined with
      cisplatin is a relatively safe and effective regimen for patients with advanced
      NSCLC.

PMID- 16965682
TI  - [A randomized control clinical trial of Euruikang (docetaxel) in treatment of
      advanced non-small cell lung cancer (NSCLC)].
AB  - BACKGROUND & OBJECTIVE: Docetaxel is one of the major drugs for advanced non
      small cell lung cancer (NSCLC) treatment in clinical use. It is reported that the
      response rate of docetaxel alone is about 20% and its major toxicity is
      myelosuppression. The study was to evaluate the efficacy and tolerability of
      docetaxel (made in Beijing) in the treatment of advanced NSCLC. METHODS: 77
      patients were randomized into two groups. In the study group, patients were
      received docetaxel (made in Beijing) 75 mg/m(2) in one hour plus cisplatin 70
      mg/m(2); while in the control group, docetaxel (made in Jiangsu) 75 mg/m(2) plus
      cisplatin 70 mg/m(2) were administrated. Treatment in the two groups was repeated
      every 3 weeks. All patients had to receive at least two cycles of chemotherapy.
      RESULTS: The objective responses in the study and control group were 28.95% and
      27.03% respectively, with no statistical difference (P>0.5). Common toxicities of
      docetaxel (made in Beijing) were grade II-III myelosuppression, grade I-II
      transaminase elevation, alopecia and hypodynamia. CONCLUSION: Docetaxel (made in
      Beijing) is an effective chemotherapy drug in advanced NSCLC treatment, which has
      the similar efficacy and toxicity to docetaxel (made in Jiangsu).

PMID- 16965683
TI  - [Study on primary hepatocellular carcinoma associated with hypersplenism treated
      by partial splenic embolization combined with hepatic arterial
      chemoembolization].
AB  - BACKGROUND & OBJECTIVE: 70-90% of patients of primary hepatocellular carcinoma
      (PHC) are associated with liver cirrhosis, portal hypertension and hypersplenism.
      The treatment of PHC is usually hampered by low or slow recovery of blood cell
      counts. This study was to investigate the effect of partial splenic embolization
      (PSE) combined with transcatheter hepatic arterial chemoembolization (TACE) for
      the treatment of PHC with portal hypertension and hypersplenism. METHODS:
      Efficacy of 26 patients with PSE combined with TACE and 26 patients with single
      TACE was observed. RESULTS: Satisfactory effects were achieved in PSE combined
      with TACE group in terms of correction of blood cell counts compared with cases
      treated with TACE alone. CONCLUSION: PSE associated with TACE is safe and
      effective for the treatment of patients with PHC associated with liver cirrhosis,
      portal hypertension and hypersplenism.

PMID- 16965684
TI  - [Prognostic factor analysis of 77 old patients with acute myelogenous leukemia].
AB  - BACKGROUND & OBJECTIVE: The manifestations of old acute myelogenous (AML)
      patients have their special biological and clinical characteristics, with lower
      response rate to therapy and shorter survival time. This study was to investigate
      the prognostic factors of elderly patients with AML retrospectively. METHODS: 77
      patients aged> or =60 years with AML from 1994 to 2005 were admitted to our study
      and all the possible prognostic factors were analyzed with Kaplan-Meier survival
      analysis. The significant factors were further analyzed by Cox proportional
      hazard model analysis. RESULTS: Seventy-two patients were evaluated. The patients
      aged 60-70 (median survival time was 350 days) had significantly longer survival
      time than those aged more than 70 (median survival time is 60 days)(P<0.001),
      which their CR ratios were 71.4% and 29.4% (P=0.001). The patients with
      performance status 0 or 1 (median survival time was 402 days) had significantly
      longer survival time than those with performance status 2, 3 or 4 (median
      survival time was 31 days)(P<0.001), which their CR ratios were 75% and 15%
      (P<0.001). The patients with primary AML (median survival time was 98 days) had
      significantly longer survival time than those with secondary AML (median survival
      time was 32 days)(P=0.007), which their CR ratios were 50% and 0% (P=0.023). The
      patients treated with sub-standard dosage of anthracycline (median survival time
      was 293 days) had significantly longer survival time than those treated with
      reduced dosage of anthracycline (median survival time was 35 days)(P=0.006),
      which their CR ratios were 63.6% and 33.3% (P=0.02). The patients with bone
      marrow blast cell ratio< or =50% (median survival time was 98 days ) had
      significantly longer survival time than those with bone marrow blast cell ratio
      >50% (median survival time was 55 days)(P=0.006). The patients with favorable
      karyotype (median survival time was 293 days) had significantly longer survival
      time than those with unfavorable or normal karyotype (median survival time was 31
      days)(P=0.005). The patients without CD34 expression (median survival time was
      201 days) had significantly longer survival time than those with CD34
      expression(median survival time was 36 days)(P<0.001). The patients with the
      peripheral blood white blood cell count (PBWBC)>10x10(9)/L (50%) had
      significantly higher CR ratio than those with PBWBC< or =10x10(9)/L
      (25%)(P=0.043). The patients received chemotherapy (50%) had significantly higher
      CR ratio than those received supportive therapy (0%)(P=0.001). In the stepwise
      COX proportional hazard regression model, all the seven factors related to OS
      remained independent and significant. CONCLUSIONS: Factors, including age >70, PS
      2 to 4, percentage of blasts in bone marrow >50%, secondary AML, unfavorable
      karyotype, expression of CD34, lower dosage.

PMID- 16965685
TI  - [Feasibility study of application of international prognostic score on prediction
      of prognosis for advanced Hodgkin's lymphoma].
AB  - BACKGROUND & OBJECTIVE: Currently, 60% patients with advanced Hodgkin's lymphoma
      could be cured by receiving standard treatments. The international prognostic
      factor project on advanced Hodgkin's lymphoma has developed a concept of
      international prognostic score (IPS) based on seven adverse prognostic factors
      consisting of male sex, age 45 years or older, stage IV disease, leukocytosis,
      lymphocytopenia, low hemoglobin and low serum albumin for newly diagnosed
      advanced Hodgkin's lymphoma patients. This study was to explore the feasibility
      of the international prognostic score in advanced Hodgkin's lymphoma. METHODS: We
      performed a retrospective review of 141 patients with untreated advanced
      Hodgkin's lymphoma in Cancer Center of Sun Yat-sen University between January
      1980 and December 2004. IPS was defined as the number of adverse prognostic
      factors presented at diagnosis. The rates of failure free survival (FFS) and
      overall survival (OS) were estimated using the method of Kaplan-Meier and
      compared according to IPS by log-rank test. Cox proportional hazard model was
      used in multivariate analysis. RESULTS: The 5-year FFS and OS for 141 advanced
      Hodgkin's lymphoma patients were 57.6%, 68.1% respectively. Estimated 5-year FFS
      was 67.7%, 63.2%, 61.8%, 34.9% for patients with 0-1, 2, 3, > or =4 of the
      adverse prognostic factors respectively. Estimated 5-year OS was 81.0%, 75.5%,
      70.3%, 42.3% for patients with 0-1, 2, 3, > or =4 of the adverse prognostic
      factors respectively. The 5-year FFS for low risk patients with IPS=0-2 and high
      risk patients with IPS> or =3 were 65.4%, 48.9% respectively (log-rank test:
      P=0.012); the 5 year OS for patients with IPS=0-2 and IPS> or =3 were 78.4%,
      57.1% respectively (log-rank test: P=0.004). Low risk patients with IPS=0-2 had
      superior overall survival than high risk patients with IPS> or =3 when treated
      with ABVD or MOPP. The FFS and OS of the advanced HL patients at high risk
      treated with ABVD were better than those treated with MOPP. Multivariate analysis
      demonstrated that B symptoms, extranodal disease and MOPP chemotherapy were
      independent adverse prognostic factors for FFS and OS. CONCLUSIONS: The IPS shows
      good prognostic power in advanced HL. High risk advanced HL patients treated with
      MOPP have inferior survival than those treated with ABVD, thus we recommend
      patients to be treated with ABVD or more intensive regimen.

PMID- 16965686
TI  - [Clinical study on haploid HLA-matched hematopoietic stem cell transplantation
      for treatment of malignant hematological disease].
AB  - BACKGROUND & OBJECTIVE: Allogeneic hematopoietic stem cell transplantation (allo
      HSCT) is the most effective method to treat malignant hematological disease.
      However the human leukocyte antigen (HLA)-matched sibling donors can be found for
      only 25%-30% patients. The probability of finding an unrelated matched donor is
      1/50000-1/100000, or even lower. If we choose haploid HLA-matched hematopoietic
      stem cell transplantation instead, we may be able to find donors for 90%
      patients. Our present study was to explore the feasibility of allo-HSCT by using
      haploid HLA-matched donor in treatment for malignant hematological disease.
      METHODS: Twenty-five patients with malignant hematological disease received allo
      HSCT with HLA 2 or 3 antigen mismatched related donors. All patients were treated
      with intensive immunosuppression, granulocyte colony stimulating factor (G-CSF)
      mobilization, antithymocyte globulin (ATG) and combination of bone marrow and
      peripheral blood stem cell transplantation. The conditioning regimen was
      intensified and prolonged by using the combination of cyclosporine (Cs) A, MMF,
      ATG and anti-CD25 antibody for graft-versus-host disease (GVHD) prophylaxis.
      RESULTS: All patients achieved sustained, full donortype engraftment. Acute GVHD
      occurred in 21 of 25 patients. Eight of them were grade I aGVHD, six grade II
      aGVHD, two grade III aGVHD and five grade IV aGVHD. The cumulative incidence of
      grade II-IV aGVHD was 48%,and grade III-IV aGVHD was 28.57%. Chronic GVHD was
      observed in 12 of 25 patients and none of them developed extensive cGVHD. Sixteen
      patients were alive and disease free, with 64.0+/- 2.98% 1 year disease-free
      survival rate. One year overall survival rate was 64.0+/-3.08%. Nine patients
      died, 1 from relapse and 8 from transplantation related mortality. CONCLUSIONS:
      Haploid HLA-matched allo-HSCT is a relatively efficient method for the treatment
      of patients with malignant hematological disease, who have no related matched
      donors. Nevertheless, strict administration should be carried out since it's a
      high risk approach.

PMID- 16965687
TI  - [Preliminary assessment of immune reconstitution after autologous peripheral
      hematopoietic stem cell transplantation (AHSCT)].
AB  - BACKGROUND & OBJECTIVES: Though high dose chemo-therapy combined with autologous
      hematopoietic stem cell transplantation (AHSCT) has made great progress on the
      treatment of chemo-sensitive malignant tumors, the relapse rate remains high.
      Successful immune reconstitution after AHSCT may reduce recurrence; therefore
      this study was to explore the characteristics of immune reconstitution after
      AHSCT and assess its feasibility in clinical use. METHODS: Twenty four cases
      after AHSCT were enrolled in our study. There were 19 Non-hodgkin Lymphoma (NHL),
      3 Hodgkin Lymphoma (HD) and 2 rhabdomyosarcoma. Nineteen cases had achieved
      complete remission (CR) while 5 partial remission (PR) before AHSCT. All cases
      were administered Interleukin (IL)-2 and Interferon (IFN)-alpha after AHSCT. Some
      patients were given thymus factor and/or CIK infusion. Phenotypes of peripheral
      blood T, B, NK subsets and immunological profile of TH1/TH2 by intracellular
      staining of cytokines after PMA/ionomycin stimulation were evaluated. RESULTS:
      75% of the cases achieved CR while 4.17% were progression of disease (PD) and
      16.67% were relapsed during the median follow-up time of 12 (2-60) months. The
      changes of immune parameters after AHSCT were as followed: (1) CD4+T cells
      (normal control 33.5+/-6.9%) started to decrease dramatically one month after
      AHSCT, which was 2.5-13% (median rate 5.6%)in the 2nd month; and then slowly
      increased to 10-20% in the 7th month, but did not return back to normal even
      after one year in all patients. In addition, reversed ratio of CD4/CD8 lasted for
      a long period of time. B cells also began to decrease 1 month after AHSCT, and
      recovered to normal in the 4th month. But B cells remained 0% in the 6th month
      and 1% in 12th month in patients treated by rituximab before receiving AHSCT. The
      ratio of NK cells was 10-20% (higher than normal controls) in the 2nd month, then
      returned to normal thereafter. (2) The cytokine secretion by T cell: there were
      48.79% patients whose TH1 was lower than normal controls or at the lower limit of
      normal range. All the patients with normal TH1 were treated by IFN-alpha or CIK
      cell infusion. TH2 was much higher than normal level among 68.29% cases and this
      abnormality lasted at least for 1 year in some cases. TH2 at normal range was
      only observed in cases receiving IFN-alpha treatment. Furthermore, IFN-alpha
      could significantly decrease TH2 level. (3) Increasing tendency of
      CD4+CD25+/CD4+, CD4+CD69+/CD4+ ratio was observed in patients received additional
      thymus factor treatment compared to those did not. CONCLUSIONS: Administration of
      CIK cells, thymus factor, IL-2 and IFN-alpha after AHSCT could improve the
      immunologic function of patients, and TH1/TH2 ratio may virtually reflect the
      immune status of patients. However more information is required to make
      prognostic assessments of immune reconstruction and the long-term survival rate.

PMID- 16965688
TI  - [Clinical evaluation of DLF, CLF and DFM regimens based on platinum compound plus
      5-fluorouracil for treatment of advanced esophageal carcinoma].
AB  - BACKGROUND & OBJECTIVE: Combination chemotherapy with 5-fluorouracil (5-FU) and
      cisplatin is regarded as the standard regimen for advanced esophageal carcinoma.
      This study was to evaluate the efficacy and safety of DLF, CLF and DFM regimens,
      based on platinum compound plus 5-fluorouracil in the treatment of advanced
      esophageal carcinoma, and to further explore prognostic factors of advanced
      esophageal carcinoma. METHODS: From October 1999 to December 2004, 98 patients
      with advanced esophageal carcinoma were enrolled in the study. They were non
      randomly assigned to receive a 2-hour infusion of folinic acid 200 mg/m(2),
      followed by a 5-FU bolus 400 mg/m(2) and 48-hour infusion of 5-FU 3,000 mg/m(2)
      every 3 weeks, combined with cisplatin 80 mg/m(2) (DLF, n=48) or with carboplatin
      AUC=5 on day 1 (CLF, n=32), or with cisplatin 80 mg/m(2), 5-fluorouracil bolus
      400 mg/m(2) on day 1-5 plus pingyangmycin 5 mg/m(2) on day 1, 3, 5 (DFM, n=18).
      Survival analysis and prognostic factors were evaluated by Kaplan-Meier method
      and Cox regression analysis. RESULTS: All 98 patients were assessable for
      response and toxicity. There were 13 complete response, 36 partial response, 45
      no changes and 4 progressive disease with a total response rate of 46.86%. The
      response rates of DLF, CLF and DFM regimens were 60.42%,46.86% and 27.78%,
      respectively (DLF vs DFM, P=0.027). The major side effects were nausea-vomiting,
      alopecia, bone marrow suppression and mucositis, and the others were uncommon.
      All side effects were tolerable and mild except for nausea-vomiting. Nausea
      vomiting was mildest in CLF among the three regimens. After a median follow-up of
      9 months, the overall median survival was 9 months (95% CI, 6.67 to 11.33
      months), the median survival of the patients treated with DLF, CLF or DFM regimen
      was 10, 9 and 7 months, respectively (P=0.7402). Better prognosis was correlated
      with good conditions of patients before chemotherapy (KPS> or =80, P=0.000) and
      metastasis to lymph node, parenchyma or bone in stead of visceral organs
      (P=0.026). There was no correlation between the prognosis and age, sex, types of
      pathology and the regimen of therapy. CONCLUSIONS: The DLF regimen is tolerable
      and more effective, thus could be recommended as a front-line standard treatment
      for advanced esophageal carcinoma. The CLF regimen is more suitable for feeble
      and older patients since it has the mildest side effects. The prognostic factors
      of advanced esophageal carcinoma include conditions before chemotherapy and the
      location of metastasis.

PMID- 16965689
TI  - [Short-term effects of chemotherapy combined with hydroxycamptothecine and
      oxaliplatin in treatment of recurrent and metastatic colorectal cancer].
AB  - BACKGROUND & OBJECTIVE: Although 5-fluarouracil (5-FU)-based chemotherapy has
      become a standard regimen for treatment of recurrent and metastatic colorectal
      cancer, the efficacy, as a second line therapy, is not high. Thus, it is
      necessary to find a new regimen as a substitute. This study was to evaluate the
      short-term effects and toxicity of combination of hydroxycamptothecine (HCPT)
      plus oxaliplatin (L-OHP) protocol in the treatment of recurrent and metastatic
      colorectal cancer. METHODS: 47 patients with pathological evidence of recurrent
      and metastatic colorectal cancer were enrolled and treated with HCPT plus L-OHP
      regimen for 86 cycles. All patients were treated with (L-OHP 130 mg/m(2), day 1
      and HCPT 6 mg/m(2), day 1-4) and the chemotherapy was repeated every 3 weeks. The
      short-term effects and side effects were evaluated after every 2 cycles for each
      patient. RESULTS: 38 cases were evaluable and RR [complete remission (CR)+partial
      remission (PR)] was 36.8% (14/38). KPS was improved in 20 cases (52.6%). In total
      86 cycles, leucopenia occurred in 59 cycles (68.6%), 18 cycles (30.5%) in grade
      III and IV, and diarrhea occurred in 48 cycles (55.8%), 18 cycles (37.5%) in
      grade III and IV. One year survival rate was 40.0% and medium overall survival
      (mOS) and medium progression free survival (mPFS) were 11.7 and 7.8 months,
      respectively. CONCLUSIONS: HCPT plus L-OHP regimen achieved relatively
      satisfactory short-term effects in the treatment for colorectal cancer patients,
      who suffered from recurrence and metastasis after the first-line chemotherapy
      with 5-FU. The main toxicities of the regimen were leucopenia and diarrhea.

PMID- 16965690
TI  - [Correlative analysis between serum dihydropyrimidine dehydrogenase, activity,
      concentration of 5-fluorouracil and adverse events in the treatment of advanced
      gastric cancer patients].
AB  - BACKGROUND & OBJECTIVE: Toxicities and their severities vary among advanced
      gastric cancer patients when they receive the same regimen containing continuous
      infusion of 5-fluorouracil (5-FU). Dihydropyrimidine dehydrogenase (DPD) is the
      key rate-limiting enzymes which is closely related to toxicities of 5-FU in
      chemotherapy. This study was to explore the relationship between activity of DPD
      and concentration of 5-FU, and their correlation to adverse events among advanced
      gastric cancer patients treated with the same regimen containing 5-FU continuous
      infusion. METHODS: Patients received the same regimen (intravenous injection of
      paclitaxel 75 mg/m(2), leucovorin 200 mg/m(2) and 5-FU 375 mg/m(2), continuous
      infusion of 5-FU 2.5 g/m2 for 46 hours every two weeks). The peripheral blood was
      collected from 36 patients with advanced gastric cancer before and after
      chemotherapy to detect the activity of DPD and concentration of 5-FU by high
      performance liquid chromatography (HPLC). Adverse events were assessed every
      cycle. RESULTS: Serum activity of DPD revealed a unimodel distribution, which
      globally fits to a guassian distribution (range 1.56-6.01). Mean and median DPD
      activity values were 2.38 and 2.13, respectively. No total DPD deficiency was
      found in the patients. The concentration of 5-FU varied from 179.2 microg/L to 1
      589.2 microg/L, which demonstrated normality distribution after a logarithmic
      transformation was applied. The DPD activity was inversely correlated with 5-FU
      concentration (r=-0.376, P=0.024). The patients with low activity of DPD were
      more frequently suffering from severe diarrhea, mucositis, and myelosuppression.
      And high level of 5-FU concentration led to the increase of adverse events.
      CONCLUSION: Pre-chemotherapy DPD activity and 5-FU concentration during
      chemotherapy vary among gastric cancer patients, which may help to prevent severe
      toxicities during the treatment.

PMID- 16965691
TI  - [The prospective study on application of parenteral nutrition with alanyl
      glutamine dipeptide in chemotherapy of gastrointestinal neoplasms patients].
AB  - BACKGROUND & OBJECTIVE: There is an argument on whether or not glutamine
      supplemented parenteral nutrition is beneficial to chemotherapy in
      gastrointestinal neoplasm patients. The aim of this study was to prospectively
      evaluate the effect of parenteral nutrition with alanyl-glutamine dipeptide on
      gastrointestinal neoplasm patients receiving chemotherapy. METHODS: This study
      was a prospective, randomized double-blind clinical trial. Seventy-two patients
      were randomly divided into study group and control group (each group had 36
      patients). The side effects during chemotherapy were observed. Serum albumin,
      serum pre-albumin, IgG, IgA, IgM, C3, C4 level were measured before chemotherapy
      and on day 4 and day 8 after chemotherapy. Nitrogen balance was also calculated
      simultaneously. RESULTS: (1) Less side effects during chemotherapy in study group
      were revealed compared to those in control group (P<0.05). (2) Serum albumin and
      pre-albumin levels were both decreased in the two groups on day 4 after
      chemotherapy, and were markedly decreased in control group on day 8 after
      chemotherapy (P<0.05). (3) IgG, IgM, IgA levels were all decreased compared with
      the test results before chemotherapy on day 4 after chemotherapy in two groups,
      and were significantly decreased in control group on day 8 after chemotherapy
      (P<0.05). C3 and C4 levels were higher in study group compared with control group
      on day 8 after chemotherapy (P<0.05). (4) Nitrogen balance in study group was
      better than that in control group (P<0.05) on day 8 after chemotherapy.
      CONCLUSIONS: Alanyl-glutamine dipeptide is beneficial to chemotherapy in
      gastrointestinal neoplasm patients. It could reduce the side effects of
      chemotherapy, which helps to improve the nutritional status, the immune function
      and the survival quality of patients during chemotherapy.

PMID- 16965692
TI  - [Effect of modified MAID regimen for patients with advanced soft tissue sarcoma].
AB  - BACKGROUND & OBJECTIVES: Clinical study suggests that 72-hour continuous infusion
      (CIV) of MAID regimen is more effective and achieves longer time of no
      progression than ADR-based two-drug regimen in advanced soft tissue sarcoma
      (ASTS) treatment, but has no improvement on the long-term survival. Because of
      the severe grade 3/4 toxicities as well as treatment-related deaths, the regimen
      has not been widely applied in ASTS. This study was to investigate the efficacy
      and toxicity of the modified MAID regimen in ASTS treatment. METHODS: In the
      modified regimen, adriamycin (ADR) was substituted with tetrahydropyranyl
      adriamycin (THP-ADR) and the application of ifosfamide (IFO) was modified. All
      enrolled patients received chemotherapy (IFO 2,000 mg . m(-2), 4h, day 1-3; mesna
      1,200 mg . m(-2) at 0, 4 and 8 hours of IFO infusion, day 1-3; THP-ADR 20 mg . m
      2 and dacarbazine (DTIC) 333.3 mg . m(-2) were mixed in the same bag or pump, CIV
      for 3 days). The therapy was repeated every 3 weeks for at least 2 cycles before
      evaluating the effects and toxicities. The patients received follow-up every 2
      months after completing 2 cycles until the study was finished. Life table was
      used to calculate long-term survival rates and time to progression. RESULTS:
      Fifty-four cases of evaluable patients had completed at least 2 cycles of
      modified MAID chemotherapy. The overall response rate was 42.59%. The toxicities
      were mild. Grade 3/4 neutropenia and thrombocytopenia were 25.93% and 16.17%,
      respectively. Neutropenia fever was 11.11%. There were no other toxicities, such
      as hepatic and renal toxicities; no central nervous system toxicity and treatment
      related deaths. During 2 year follow-up, time to progression was 7 months, 1- and
      2- year survival rates were 61.11% and 36.36%, respectively. CONCLUSIONS:
      Modified MAID regimen simplifies the application of treatment procedure compared
      with original regimen, which three drugs have to be CIV simultaneously. Moreover
      the modified MAID regimen has better survival rates in ASTS, with milder toxicity
      and better tolerance.

PMID- 16965693
TI  - [Analysis of antineoplastic drugs used in Cancer Center, Sun Yat-sen University,
      during the period of 1996-2005].
AB  - BACKGROUND & OBJECTIVE: Lately, the prevention, treatment and research of cancer
      have developed rapidly. Antineoplastic drugs have become one of the major
      measures for cancer therapy. Many new antineoplastic drugs have been discovered
      and prepared, and used to treat tumors. Cancer Center of Sun Yat-sen University
      is one of the biggest cancer hospitals in South China. The use of antineoplastic
      drugs of this center can reflect changes in this area. This study was to analyze
      and evaluate the situation and trend of antineoplastic drugs used in Cancer
      Center, Sun Yat-sen University from 1996 and 2005, in order to provide references
      for the rational use of drugs in clinical application. METHODS: Consumption of
      antineoplastic drugs was analyzed by sum and defined daily dose (DDDs) ranking.
      RESULTS: The costs of antineoplastic drugs occupied 31.0%-48.8% of all drugs from
      1996 to 2005; and the average increasing ratio is 21.5%. The cost rate of anti
      cancer vegetable drugs and other genus increased the quickest, while the total
      costs of alkylate increased the slowest during the ten years. Some new
      monoantibodies and gene drugs were continuously applied in clinical use.
      CONCLUSION: The direction of the research and development of antineoplastic drugs
      is towards high efficiency, low toxicity and individualized use.

PMID- 16965694
TI  - [New advances in clinical trials of cancer vaccines].
AB  - Currently, a range of cancer vaccine strategies are being tested including those
      using peptides, DNA/RNA, viral vectors, tumor cells, pulsed dendritic cells etc.
      Cancer vaccines can activate, recover or power the immune system to kill and
      eliminate tumor cells by expressing specific cancer antigens. New cancer vaccines
      must be first studied in animals and then tested for safety and effectiveness in
      three phases of clinical trials. Cancer vaccines have shown promise in clinical
      trials with many types of cancer. There are a lot of vaccines which can initiate
      a powerful immune response in some patients, and are generally well tolerated.
      Although there are dozens of cancer vaccines in advanced clinical trials, yet
      only a few phase III studies have been completed. Because they have failed to
      meet the goals of safety and effectiveness, this makes cancer vaccines still in
      an experimental stage. A number of promising new cancer vaccines have entered
      clinical trials, and we eagerly await their findings. In this article we reviewed
      new advances in clinical trials and the perspective in clinical use of cancer
      vaccines.

PMID- 16965695
TI  - Invasive Enterobacter sakazakii disease in infants.
AB  - Enterobacter sakazakii kills 40%-80% of infected infants and has been associated
      with powdered formula. We analyzed 46 cases of invasive infant E. sakazakii
      infection to define risk factors and guide prevention and treatment. Twelve
      infants had bacteremia, 33 had meningitis, and 1 had a urinary tract infection.
      Compared with infants with isolated bacteremia, infants with meningitis had
      greater birthweight (2,454 g vs. 850 g, p = 0.002) and gestational age (37 weeks
      vs. 27.8 weeks, p = 0.02), and infection developed at a younger age (6 days vs.
      35 days, p<0.001). Among meningitis patients, 11 (33%) had seizures, 7 (21%) had
      brain abscess, and 14 (42%) died. Twenty-four (92%) of 26 infants with feeding
      patterns specified were fed powdered formula. Formula samples associated with 15
      (68%) of 22 cases yielded E. sakazakii; in 13 cases, clinical and formula strains
      were indistinguishable. Further clarification of clinical risk factors and
      improved powdered formula safety is needed.

PMID- 16965696
TI  - Venezuelan equine encephalitis virus transmission and effect on pathogenesis.
AB  - Quantifying the dose of an arbovirus transmitted by mosquitoes is essential for
      designing pathogenesis studies simulating natural infection of vertebrates.
      Titration of saliva collected in vitro from infected mosquitoes may not
      accurately estimate titers transmitted during blood feeding, and infection by
      needle injection may affect vertebrate pathogenesis. We compared the amount of
      Venezuelan equine encephalitis virus collected from the saliva of Aedes
      taeniorhynchus to the amount injected into a mouse during blood feeding. Less
      virus was transmitted by mosquitoes in vivo (geometric mean 11 PFU) than was
      found for comparable times of salivation in vitro (mean saliva titer 74 PFU). We
      also observed slightly lower early and late viremia titers in mice that were
      needle injected with 8 PFU, which represents the low end of the in vivo
      transmission range. No differences in survival were detected, regardless of the
      dose or infection route.

PMID- 16965697
TI  - Bat-transmitted human rabies outbreaks, Brazilian Amazon.
AB  - We describe 2 bat-transmitted outbreaks in remote, rural areas of Portel and
      Viseu Municipalities, Para State, northern Brazil. Central nervous system
      specimens were taken after patients' deaths and underwent immunofluorescent assay
      and histopathologic examination for rabies antigens; also, specimens were
      injected intracerebrally into suckling mice in an attempt to isolate the virus.
      Strains obtained were antigenically and genetically characterized. Twenty-one
      persons died due to paralytic rabies in the 2 municipalities. Ten rabies virus
      strains were isolated from human specimens; 2 other cases were diagnosed by
      histopathologic examination. Isolates were antigenically characterized as
      Desmodus rotundus variant 3 (AgV3). DNA sequencing of 6 strains showed that they
      were genetically close to D. rotundus-related strains isolated in Brazil. The
      genetic results were similar to those obtained by using monoclonal antibodies and
      support the conclusion that the isolates studied belong to the same rabies cycle,
      the virus variants found in the vampire bat D. rotundus.

PMID- 16965698
TI  - Streptococcus suis sequence type 7 outbreak, Sichuan, China.
AB  - An outbreak of Streptococcus suis serotype 2 emerged in the summer of 2005 in
      Sichuan Province, and sporadic infections occurred in 4 additional provinces of
      China. In total, 99 S. suis strains were isolated and analyzed in this study: 88
      isolates from human patients and 11 from diseased pigs. We defined 98 of 99
      isolates as pulse type I by using pulsed-field gel electrophoresis analysis of
      SmaI-digested chromosomal DNA. Furthermore, multilocus sequence typing classified
      97 of 98 members of the pulse type I in the same sequence type (ST), ST-7.
      Isolates of ST-7 were more toxic to peripheral blood mononuclear cells than ST-1
      strains. S. suis ST-7, the causative agent, was a single-locus variant of ST-1
      with increased virulence. These findings strongly suggest that ST-7 is an
      emerging, highly virulent S. suis clone that caused the largest S. suis outbreak
      ever described.

PMID- 16965699
TI  - Carbapenem resistance in Klebsiella pneumoniae not detected by automated
      susceptibility testing.
AB  - Detecting beta-lactamase-mediated carbapenem resistance among Klebsiella
      pneumoniae isolates and other Enterobacteriaceae is an emerging problem. In this
      study, 15 blaKPC-positive Klebsiella pneumoniae that showed discrepant results
      for imipenem and meropenem from 4 New York City hospitals were characterized by
      isoelectric focusing; broth microdilution (BMD); disk diffusion (DD); and
      MicroScan, Phoenix, Sensititre, VITEK, and VITEK 2 automated systems. All 15
      isolates were either intermediate or resistant to imipenem and meropenem by BMD;
      1 was susceptible to imipenem by DD. MicroScan and Phoenix reported 1 (6.7%) and
      2 (13.3%) isolates, respectively, as imipenem susceptible. VITEK and VITEK 2
      reported 10 (67%) and 5 (33%) isolates, respectively, as imipenem susceptible. By
      Sensititre, 13 (87%) isolates were susceptible to imipenem, and 12 (80%) were
      susceptible to meropenem. The VITEK 2 Advanced Expert System changed 2 imipenem
      MIC results from >16 ?g/mL to <2 ?g/mL but kept the interpretation as resistant.
      The recognition of carbapenem-resistant K. pneumoniae continues to challenge
      automated susceptibility systems.

PMID- 16965700
TI  - VEB-1 Extended-spectrum beta-lactamase-producing Acinetobacter baumannii, France.
AB  - VEB-1 extended-spectrum beta-lactamase-producing Acinetobacter baumannii was
      responsible for an outbreak in hospitals in France. A national alert was
      triggered in September 2003 when 4 hospitals reported clusters of A. baumannii
      infection with similar susceptibility profiles. Case definitions and laboratory
      guidelines were disseminated, and prospective surveillance was implemented;
      strains were sent to a single laboratory for characterization and typing. From
      April 2003 through June 2004, 53 hospitals reported 290 cases of A. baumannii
      infection or colonization; 275 isolates were bla(VEB-1)-positive and clonally
      related. Cases were first reported in 5 districts of northern France, then in 10
      other districts in 4 regions. Within a region, interhospital spread was
      associated with patient transfer. In northern France, investigation and control
      measures led to a reduction of reported cases after January 2004. The national
      alert enabled early control of new clusters, demonstrating the usefulness of
      early warning about antimicrobial drug resist.

PMID- 16965701
TI  - Macrolide resistance in adults with bacteremic pneumococcal pneumonia.
AB  - We conducted a case-control study of adults with bacteremic pneumococcal
      pneumonia to identify factors associated with macrolide resistance. Study
      participants were identified through population-based surveillance in a 5-county
      region surrounding Philadelphia. Forty-three hospitals contributed 444 patients,
      who were interviewed by telephone regarding potential risk factors. In
      multivariable analyses, prior exposure to a macrolide antimicrobial agent (odds
      ratio [OR] 2.8), prior flu vaccination (OR 2.0), and Hispanic ethnicity (OR 4.1)
      were independently associated with an increased probability of macrolide
      resistance, and a history of stroke was independently associated with a decreased
      probability of macrolide resistance (OR 0.2). Fifty-five percent of patients with
      macrolide-resistant infections reported no antimicrobial drug exposure in the
      preceding 6 months. Among patients who reported taking antimicrobial agents in
      the 6 months preceding infection, failure to complete the course of prescribed
      drugs was associated with an increased probability of macrolide resistance (OR
      3.4).

PMID- 16965703
TI  - Virulent epidemics and scope of healthcare workers' duty of care.
AB  - The phrase "duty of care" is, at best, too vague and, at worst, ethically
      dangerous. The nature and scope of the duty need to be determined, and
      conflicting duties must be recognized and acknowledged. Duty of care is neither
      fixed nor absolute but heavily dependent on context. The normal risk level of the
      working environment, the healthcare worker's specialty, the likely harm and
      benefits of treatment, and the competing obligations deriving from the worker's
      multiple roles will all influence the limits of the duty of care. As experts
      anticipate the arrival of an avian influenza pandemic in humans, discussion of
      this matter is urgently needed.

PMID- 16965702
TI  - Antibody response to Pneumocystis jirovecii major surface glycoprotein.
AB  - We conducted a prospective pilot study of the serologic responses to overlapping
      recombinant fragments of the Pneumocystis jirovecii major surface glycoprotein
      (Msg) in HIV-infected patients with pneumonia due to P. jirovecii and other
      causes. Similar baseline geometric mean antibody levels to the fragments measured
      by an ELISA were found in both groups. Serum antibodies to MsgC in P. jirovecii
      patients rose to a peak level 3-4 weeks (p<0.001) after recovery from
      pneumocystosis; baseline CD4+ count > or =50 cells/microL and first episode of
      pneumocystosis were the principal host factors associated with this rise (both
      p<0.001). Thus, MsgC shows promise as a serologic reagent and should be tested
      further in clinical and epidemiologic studies.

PMID- 16965704
TI  - Human and canine pulmonary blastomycosis, North Carolina, 2001-2002.
AB  - We investigated a cluster of blastomycosis in 8 humans and 4 dogs in a rural
      North Carolina community. Delayed diagnosis, difficulty isolating Blastomyces
      dermatitidis in nature, and lack of a sensitive and specific test to assess
      exposure make outbreaks of this disease difficult to study.

PMID- 16965705
TI  - West Nile virus epizootiology, central Red River Valley, North Dakota and
      Minnesota, 2002-2005.
AB  - West Nile virus (WNV) epizootiology was monitored from 2002 through 2005 in the
      area surrounding Grand Forks, North Dakota. Mosquitoes were tested for infection,
      and birds were surveyed for antibodies. In 2003, WNV was epidemic; in 2004, cool
      temperatures precluded WNV amplification; and in 2005, immunity in passerines
      decreased, but did not preclude, WNV amplification.

PMID- 16965706
TI  - O'nyong-nyong Virus, Chad.
AB  - We report the first laboratory-confirmed human infection with O'nyong-nyong virus
      in Chad. This virus was isolated from peripheral blood mononuclear cells of a
      patient with evidence of a seroconversion to a virus related to Chikungunya
      virus. Genome sequence was partly determined, and phylogenetic studies were
      conducted.

PMID- 16965707
TI  - Human bocavirus in French children.
AB  - Human bocavirus (HBoV), a new member of the genus Bocavirus in the family
      Parvoviridae, has been recently associated with respiratory tract infections. We
      report the epidemiologic and clinical features observed from a 1-year
      retrospective study of HBoV infection in young children hospitalized with a
      respiratory tract infection.

PMID- 16965708
TI  - Bocavirus infection in hospitalized children, South Korea.
AB  - This study presents the first evidence of human bocavirus infection in South
      Korean children. The virus was detected in 27 (8.0%) of 336 tested specimens,
      including 17 (7.5%) of 225 virus-negative specimens, collected from children with
      acute lower respiratory tract infection.

PMID- 16965709
TI  - Changing pattern of visceral leishmaniasis, United Kingdom, 1985-2004.
AB  - A 20-year (1985-2004) retrospective review of 39 patients with imported visceral
      leishmaniasis found that tourism to Mediterranean countries and HIV infection
      were associated with visceral leishmaniasis. Diagnosis was often delayed.
      Treatment with liposomal amphotericin B has improved prognosis. Visceral
      leishmaniasis should be made a reportable disease.

PMID- 16965710
TI  - Mental status after West Nile virus infection.
AB  - Mental status after acute West Nile virus infection has not been examined
      objectively. We compared Telephone Interview for Cognitive Status scores of 116
      patients with West Nile fever or West Nile neuroinvasive disease. Mental status
      was poorer and cognitive complaints more frequent with West Nile neuroinvasive
      disease (p = 0.005).

PMID- 16965711
TI  - Human metapneumovirus, Australia, 2001-2004.
AB  - We examined 10,025 respiratory samples collected for 4 years (2001-2004) and
      found a 7.1% average annual incidence of human metapneumovirus. The epidemic peak
      of infection was late winter to spring, and genotyping showed a change in
      predominant viral genotype in 3 of the 4 years.

PMID- 16965712
TI  - Methicillin-resistant Staphylococcus aureus in children, Taiwan.
AB  - Highly virulent community-acquired methicillin-resistant Staphylococcus aureus
      (CA-MRSA) with Panton-Valentine leukocidin (PVL) is common worldwide. Using
      antimicrobial drug susceptibility testing, staphylococcal cassette chromosome mec
      typing, exotoxin profiling, and pulsed-field gel electrophoresis typing, we
      provide evidence that supports the relationship between nasal strains of PVL
      positive MRSA and community-acquired disease.

PMID- 16965713
TI  - Incubation period of hantavirus cardiopulmonary syndrome.
AB  - The potential incubation period from exposure to onset of symptoms was 7-39 days
      (median 18 days) in 20 patients with a defined period of exposure to Andes virus
      in a high-risk area. This period was 14-32 days (median 18 days) in 11 patients
      with exposure for <48 hours.

PMID- 16965714
TI  - Bat-associated rabies virus in Skunks.
AB  - Rabies was undetected in terrestrial wildlife of northern Arizona until 2001,
      when rabies was diagnosed in 19 rabid skunks in Flagstaff. Laboratory analyses
      showed causative rabies viruses associated with bats, which indicated cross
      species transmission of unprecedented magnitude. Public health infrastructure
      must be maintained to address emerging zoonotic diseases.

PMID- 16965715
TI  - Fecal viral load and norovirus-associated gastroenteritis.
AB  - We report the median cDNA viral load of norovirus genogroup II is >100-fold
      higher than that of genogroup I in the fecal specimens of patients with norovirus
      associated gastroenteritis. We speculate that increased cDNA viral load accounts
      for the higher transmissibility of genogroup II strains through the fecal-oral
      route.

PMID- 16965716
TI  - Rickettsia felis in Xenopsylla cheopis, Java, Indonesia.
AB  - Rickettsia typhi and R. felis, etiologic agents of murine typhus and fleaborne
      spotted fever, respectively, were detected in Oriental rat fleas (Xenopsylla
      cheopis) collected from rodents and shrews in Java, Indonesia. We describe the
      first evidence of R. felis in Indonesia and naturally occurring R. felis in
      Oriental rat fleas.

PMID- 16965717
TI  - Avian influenza among waterfowl hunters and wildlife professionals.
AB  - We report serologic evidence of avian influenza infection in 1 duck hunter and 2
      wildlife professionals with extensive histories of wild waterfowl and game bird
      exposure. Two laboratory methods showed evidence of past infection with influenza
      A/H11N9, a less common virus strain in wild ducks, in these 3 persons.

PMID- 16965718
TI  - OFFLU network on avian influenza.
AB  - OFFLU is the name of the network of avian influenza expertise inaugurated jointly
      in 2005 by the Food and Agriculture Organization of the United Nations and the
      World Organisation for Animal Health. Achievements and constraints to date and
      plans for the future are described.

PMID- 16965719
TI  - TROPHY: a trial that may change clinical practice.

PMID- 16965720
TI  - Angiotensin-receptor blockers for prehypertension.

PMID- 16965721
TI  - The value of home blood pressure monitoring.
AB  - Home blood pressure (BP) monitoring has become popular and acceptable. The value
      of home BP monitoring has been recognized, because it has some potential
      advantages over office BP. Home BP monitoring is more accurate and reproducible,
      has a better prognostic value, and increases patients' compliance with treatment.
      Home BP monitoring should be performed with an adequate device, following a
      standardized procedure. The automated arm-cuff-oscillometric devices are
      recommended currently, and home BP should be measured at least twice daily, in
      the morning and in the evening. Home BP monitoring has revealed the phenomena of
      "white-coat hypertension," "masked hypertension," and "morning hypertension," and
      it is useful for their management. In the future, home BP monitoring will be an
      essential aspect of clinical practice.

PMID- 16965722
TI  - Estrogen and hypertension.
AB  - Menopause is accompanied by a dramatic rise in the prevalence of hypertension in
      women, suggesting a protective role of endogenous estradiol on blood pressure
      (BP). Both animal experimental and human clinical investigations suggest that
      estrogen engages several mechanisms that protect against hypertension, such as
      activation of the vasodilator pathway mediated by nitric oxide and prostacyclin
      and inhibition of the vasoconstrictor pathway mediated by the sympathetic nervous
      system and angiotensin. However, emerging evidence from recent clinical trials
      indicates a small increase, rather than decrease, in systolic BP with oral
      estrogen administration in postmenopausal women, without any detectable effect on
      diastolic BP. Mechanisms underlying this selective rise in systolic BP in
      postmenopausal women and oral contraceptive-induced hypertension in premenopausal
      women remain unknown, but the rise may be related to supraphysiologic
      concentration of estrogen in the liver. To date, transdermal delivery of
      estrogen, which avoids the first-pass hepatic metabolism of estradiol, appears to
      have a small BP-lowering effect in postmenopausal women and may be a safer
      alternative in hypertensive women.

PMID- 16965723
TI  - Treatment of isolated systolic hypertension.
AB  - Isolated systolic hypertension (ISH) is the dominant form of hypertension in the
      elderly. It is associated with increased arterial pulse pressure, to which an
      early-returning and magnified pulse-wave reflection makes an important
      contribution. Treatment of ISH with diuretics, calcium channel blockers (CCBs),
      and angiotensin II inhibitors is effective in reducing systolic blood pressure,
      preventing cardiovascular morbid events, and lowering mortality; these agents may
      have to be used in combination to achieve the systolic blood pressure goal of <
      140 mm Hg. Treatment with beta-blockers appears to be less effective. The
      relative efficacy of various classes of antihypertensive drugs for lowering pulse
      pressure and systolic blood pressure is determined in part by their differing
      abilities to reduce pulse-wave reflection. In patients with ISH that is
      refractory to dual or triple therapy, measurement of the reflected wave by
      applanation tonometry may be useful in determining which additional
      antihypertensive agent to use.

PMID- 16965724
TI  - Expanding the definition of hypertension to incorporate global cardiovascular
      risk.
AB  - Recent epidemiologic analyses have changed the way that hypertension is viewed.
      Cardiovascular risk has been found to be elevated at levels of blood pressure
      previously believed to be normal and not imparting additional risk. Furthermore,
      the approach to hypertension has been shifted from viewing and treating it in
      isolation to a more comprehensive approach that incorporates a focus on global
      cardiovascular risk and the risk factors commonly associated with having an
      elevated blood pressure. However, control rates not only for hypertension but
      also for associated risk factors, such as hyperlipidemia and diabetes, remain
      abysmal, providing an even greater challenge to providers of care. To change this
      alarming trend, physicians must become aggressive in using the available
      armamentarium of lifestyle modifications and drugs in treating hypertension and
      other risk factors that increase the burden of atherosclerosis.

PMID- 16965725
TI  - The continuum of blood pressure risk: when is the best time to intervene?

PMID- 16965726
TI  - Review of resistant hypertension.
AB  - Despite the prevalence of hypertension, blood pressure (BP) can be controlled
      with effective therapy in most patients. However, in a small percentage of the
      hypertensive population, BP remains refractory to therapeutic measures. In such
      patients who have so-called "resistant" hypertension, proper evaluation and
      assessment have to be undertaken to improve the BP control. There are some
      situations or factors that may make hypertension control difficult in some
      patients. Therefore, it is necessary to identify possible reasons for the loss of
      BP control and rectify them to achieve normotension. In addition to indicated
      work-up for secondary causes, aggressive treatment (nonpharmacologic and
      pharmacologic) of hypertension is required to prevent excessive morbidity and
      mortality in this special population.

PMID- 16965727
TI  - Metabolic safety of antihypertensive drugs: myth versus reality.
AB  - Treatment of hypertension with the major available antihypertensive classes
      results in a significant improvement in cardiovascular morbidity and mortality.
      However, there is controversy about whether specific classes of drug therapy have
      deleterious or beneficial effects on glucose and lipid metabolism. Myths and
      misconceptions have thus arisen. Although "old" classes of antihypertensives,
      such as diuretics and beta-blockers, seem to have deleterious effects on glucose
      and lipid metabolism, the "newer" agents appear to have either neutral or
      beneficial profiles. The long-term significance of these metabolic changes is
      still debated. It is known that insulin resistance plays a major role in the
      pathogenesis of hypertension and type 2 diabetes mellitus. There is increasing
      evidence that blocking the renin-angiotensin-aldosterone system by using
      angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers
      favorably affects insulin sensitivity and, accordingly, decreases the incidence
      of new-onset type 2 diabetes mellitus.

PMID- 16965728
TI  - Lessons from the African-American Study of Kidney Disease and Hypertension: an
      update.
AB  - Hypertension is the second leading attributable cause of end-stage renal disease
      in the United States today. The African-American Study of Kidney Disease and
      Hypertension was a randomized, double-blind, controlled trial designed to
      determine whether strict blood pressure (BP) control, angiotensin-converting
      enzyme inhibitor (ACEI)-based, or calcium channel blocker (CCB)-based regimens
      were superior to less strict BP control and beta-blocker (BB)-based regimens,
      respectively. The study enrolled 1093 African Americans with hypertensive
      nephrosclerosis and followed them for 4 years with repeated direct measurement of
      glomerular filtration rate (GFR) and monitoring of end points, including rapid
      decline in GFR, end-stage kidney disease, and death. From this landmark study, we
      learned that strict BP control is achievable in this study population, but it did
      not slow progression of kidney disease, and we learned that an ACEI-based therapy
      was superior to either a BB- or CCB-based regimen. In addition, we learned that
      proteinuria is the most important predictor of progression of kidney disease;
      ACEI and CCB have differential effects on proteinuria; and a CCB-based regimen
      combined with strict BP control may be the next best choice to an ACEI-based
      regimen in this population.

PMID- 16965729
TI  - Current understanding of optimal blood pressure goals in dialysis patients.
AB  - The hemodialysis population is associated with a very low survival rate, with
      myocardial infarctions and strokes accounting for most of the increased
      mortality. Recent observational studies demonstrate a paradoxical relationship
      between increasing blood pressure and increasing mortality. Hypertension treated
      with antihypertensive medications unequivocally reduces cerebrovascular risk, but
      demonstration of a survival benefit for cardiovascular mortality has proven more
      difficult to demonstrate. Increased pulse pressure is caused by inadequate
      dialysis treatment that increases arterial wall stiffness and afterload, and
      decreases coronary perfusion. The disproportionate representation of diastolic
      dysfunction and coronary artery atherosclerosis may explain why increased pulse
      pressure is associated with higher cardiovascular risk for the dialysis
      population. Optimum blood pressure control has not been established, due to a
      lack of prospective studies targeting blood pressure reduction. Opinion-based
      recommendations are offered, but goals should be individualized based on a
      complete assessment of prevailing comorbidities and should target normalization
      of the pulse pressure.

PMID- 16965730
TI  - Electrical stimulation of the carotid sinus for the treatment of resistant
      hypertension.
AB  - Hypertension is a major cause of morbidity and mortality worldwide. Despite a
      myriad of oral agents, many patients fail to reach their target blood pressure.
      Electrical stimulation of the carotid sinus, an old therapeutic concept, lowers
      blood pressure by initiating the baroreflex and reducing sympathetic tone. Recent
      evidence suggests that the baroreflex is more important in the setting of chronic
      hypertension than originally believed. The carotid stimulator may be a safe and
      effective therapeutic option for patients with resistant hypertension.

PMID- 16965734
TI  - [Post-absorption/metabolism multicompound drug: a new approach to modernization
      of Chinese herbal medicine].
AB  - A major hurdle that humbles the modernization of traditional Chinese herbal
      medicine (CHM) is the inconsistency of chemical composition, which is inevitable
      due to the natural origins of CHM. Here I propose a concept of a new category of
      drugs, named "post-absorption/metabolism multicompound drug (PAMD)" that will
      meet every standard of modern pharmaceuticals, yet maintain the fundamental
      principle of traditional Chinese medicine, which is an integrative therapeutic
      approach through multiple mechanisms by a cocktail of various herbs. The PAMD
      concept is based on the fact that the most of chemical ingredients in an orally
      taken CHM remedy may never enter the blood stream owing to the poor
      gastrointestinal absorption. Only a few original ingredients or, most likely, a
      few metabolites of those absorbed ingredients are found in the blood or target
      organs. The compounds after the absorption/metabolic process are the only ones
      responsible for pharmacological functions of the remedy. Given the limited number
      of species, those compounds, once isolated and tested for their pharmacological
      activity, can be formulated with designed ratios to form new drugs that should
      theoretically possess an equivalent or better therapeutic efficacy than the
      original CHM remedy. Strategies of developing PAMDs and possible difficulties are
      also discussed.

PMID- 16965735
TI  - [Standardization of syndrome differentiation based on stages for breast cancer: a
      significant and updating topic on mastology of traditional Chinese medicine].
AB  - The incidence of breast cancer increased rapidly in recent years. Breast cancer
      has become the most frequent malignant tumor of female especially in the
      developed regions. Traditional Chinese medicine (TCM) is effective in treating
      breast cancer, but its theories appear hysteretic, restricting the progress in
      clinical practice, teaching and research of TCM in the treatment of breast
      cancer. This article described the significance and urgency to work out the
      standardization of syndrome differentiation based on stages for breast cancer and
      put it into practice. It also analyzed the foundations, ideas and approaches of
      the research of standardization of syndrome differentiation based on stages for
      breast cancer in light of the changes of spectrum of diseases, the weaknesses of
      modern medicine in treating breast cancer, and the existed problems in the update
      clinical practice.

PMID- 16965731
TI  - New drugs for hypertension: what do they offer?
AB  - A new drug might make a positive contribution to existing therapies for
      hypertension by: 1) reducing blood pressure (BP) via a novel pharmacologic
      mechanism; 2) possessing pharmacologic or pharmacokinetic properties that make it
      superior to other members of its class; or 3) facilitating BP control in
      refractory patients. In this paper, we review four experimental agents that
      promise to advance therapeutics by one of these mechanisms. Aliskiren is the
      first in a new class of potent, orally effective renin inhibitors. Aliskiren
      produces dose-dependent BP reduction with few side effects and constitutes a
      novel pharmacologic approach to renin-angiotensin-aldosterone inhibition.
      Nebivolol is a third-generation, cardioselective beta-blocker that produces
      vasodilation and improves endothelial function via the l-arginine/nitric oxide
      pathway. Clevidipine is an ultra-short-acting, vascular-selective,
      dihydropyridine calcium antagonist that is being developed for intravenous use in
      acute hospitalized patients. Darusentan is an endothelin(A) selective endothelin
      receptor antagonist that is effective in achieving BP control in a significant
      percentage of patients who remain uncontrolled despite treatment with three or
      more antihypertensive drugs.

PMID- 16965736
TI  - [Applications and approved projects on traditional Chinese medicine in National
      Natural Science Foundation of China in 2005].
AB  - National Natural Science Foundation of China (NSFC) is an important part of
      national system for innovation, which provides financial assistance mainly for
      the basic and applied researches of natural sciences, especially for the
      researchers who work in the learning institutions and the agencies of scientific
      research with advanced facilities. This paper summarized the applications and
      approved projects on traditional Chinese medicine in NFSC in 2005. We initially
      analyzed the growth, quality, characteristics, tendency and problems of these
      items.

PMID- 16965737
TI  - Critical appraisal of clinical studies in Chinese herbal medicine.
AB  - The use of complementary and alternative medicine (CAM) is currently widespread
      and appears to be growing. As an increasing proportion of the population turns to
      CAM therapies, whether singly or in combination with allopathic medicine, the
      need for quality research in this area is reinforced. Much of this research
      consists of clinical studies aimed primarily at clinicians, yet challenges
      arising from poor methodological quality will occur when interpreting study
      findings and their implications. For clinicians to be effective consumers of the
      scientific literature, familiarization with the principles of evidence-based
      medicine (EBM) is essential. The goal of this review is to introduce clinicians
      to the concept of critical appraisal of clinical studies and foster critical
      thinking when reading research articles in order to best evaluate and incorporate
      study findings into their daily practice. Topics discussed in this article
      include: (1) fundamentals of EBM; (2) types of clinical studies; (3) hierarchy of
      evidence; (4) Consolidated Standard of Randomized Trials (CONSORT) statement to
      evaluate the quality of reporting in randomized controlled trials (RCTs); (5)
      methodologic quality rating scales for RCTs; and (6) issues specific to
      evaluating studies of Chinese herbal medicine.

PMID- 16965738
TI  - [Curative effects of Fuzheng Huayu capsules on hepatic fibrosis and the
      functional mechanisms: a review].
AB  - Deficiency of Qi (healthy energy) and blood stasis are the basic pathological
      changes of hepatic fibrosis according to the theories of traditional Chinese
      medicine. Fuzheng Huayu Capsule, a compound Chinese herbal medicine for hepatic
      fibrosis, is produced in the light of this pathological mechanism. More than a
      decade of clinical studies and experimental researches show that this medicine
      has effects of protecting hepatic cells, relieving liver injury, and controlling
      the development of hepatic fibrosis. It has definite functional mechanisms on
      anti-hepatic fibrosis. It is a safe and effective medicine for hepatic fibrosis,
      and deserves to be well introduced to clinic.

PMID- 16965739
TI  - [Significance and necessity of developing quality of life questionnaire for
      cancer patients adapting to traditional Chinese medicine].
AB  - The clinical evaluation system for therapeutic effects of tumor, which focuses on
      survival period and tumor response rate, has been proved not very proper for
      evaluating the therapeutic effects of traditional Chinese medicine (TCM). Quality
      of life (QOL) has been introduced into the effective evaluation system of TCM and
      integrative medicine because of its similarity in concept and extension with TCM
      at theory basis, syndrome differentiation-treatment, and evaluation of
      therapeutic effects. But there are no QOL questionnaires which can evaluate the
      therapeutic effects of TCM and integrative medicine precisely. This article
      discussed the necessity and significance of developing QOL questionnaire special
      for TCM.

PMID- 16965741
TI  - [Correlation between the width of lingual vein and the changes of hemodynamics of
      portal system in patients with primary liver cancer].
AB  - OBJECTIVE: To explore the correlation between the width of lingual varix and
      changes of hemodynamics of portal system in patients with primary liver cancer so
      as to supply the data for the forecast of portal hypertension by observing
      lingual varix. METHODS: The diameter of lingual vein (Dlv) was measured by
      vernier caliper as dependent variable, and the diameters and indexes of
      hemodynamics of portal vessels were measured by Doppler as independent variables,
      then a multipe stepwise analysis was performed. RESULTS: The diameters of portal
      vein (Dpv) and splenic vein (Dsv) entered the formula Dlv (mm) = 0.185 + 0.311
      Dsv (mm) + 0.236 Dpv (mm) when the entry and removal values were alpha(in)=0.10
      and alpha(out)=0.15, respectively. CONCLUSION: The width of lingual vein is
      closely correlated with the diameters of portal vein and splenic vein in patients
      with primary liver cancer.

PMID- 16965740
TI  - [Immunoregulation and short-term therapeutic effects of super-selective intra
      arterial chemotherapy combined with traditional Chinese drugs on gastric cancer
      patients].
AB  - OBJECTIVE: To investigate the immunoregulation and short-term therapeutic effects
      of super-selective intra-arterial chemotherapy combined with Fuzheng Kang'ai
      Granules, a compound Chinese herbal medicine, on patients with late gastric
      cancer. METHODS: Forty patients with late gastric antrum cancer were randomly
      divided into study group and control group. Patients in the study group were
      orally administered Fuzheng Kang'ai Granules 48 hours after the first super
      selective left gastric artery chemotherapy with high-dose drugs (EAP regime:
      VP(16) 100 mg/m(2) + epirubicin 60 mg/m(2) + carboplatin 200 mg/m(2)), while
      patients in the control group were only administered the same local artery
      chemotherapy as in the study group. RESULTS: The short-term therapeutic efficacy
      in the study group and control group were 82.5% and 57.5% respectively (P<0.01).
      The occurrence rates of side effects in the study group were significantly lower
      than those in the control group (P<0.01). The Karnofsky score of life quality of
      the study group was obviously higher than that of the control group after
      treatment (P<0.05). The half survival time and one year survival rate in the
      study group and control group were (24.9 +/- 1.36) month, 70% (28/40) and (13.7
      +/- 0.72) month, 35% (14/40) respectively. They were significantly improved in
      the study group compared with the control group (P<0.01). The levels of cytokines
      interleukin 2 (IL-2), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma
      (IFN-gamma) after treatment in the study group were significantly higher than
      those before treatment (P<0.05 or P<0.01), as well as than those after treatment
      in the control group (P<0.01). On the other hand, the level of immune inhibitory
      factor soluble interleukin-2 receptor (sIL-2R) after treatment in the study group
      was lower than that before treatment, as well as than that after treatment in the
      control group (P<0.01). CONCLUSIONS: The super-selective intra-arterial
      chemotherapy combined with Fuzheng Kang'ai Granules has good short-term
      therapeutic efficiency and few side effects for patients with late gastric antrum
      cancer. It can significantly improve the life quality, extend the survival
      period, and improve the survival rate in patients with late gastric antrum
      cancer, which may be due to the up-regulation of the immune regulating factors
      such as IL-2, TNF-alpha, IFN-gamma and down-regulation of the immune inhibitory
      factor sIL-2R.

PMID- 16965742
TI  - Evidence for Oldenlandia diffusa-evoked cancer cell apoptosis through superoxide
      burst and caspase activation.
AB  - BACKGROUND & OBJECTIVE: Oldenlandia diffusa (Bai Hua She She Cao) is one of the
      herbs most commonly used in traditional Chinese medicine for treating cancer.
      Various studies using the herb alone or in combination with other therapy plans
      have evidenced the effectiveness of the herb in the management of cancers of
      different tissue origin. However, the mechanisms underlying its anti-cancer
      activity are unknown. In the present study, we attempted to investigate the
      apoptotic activity of crude extracts of the herb as well as the possible
      molecular pathways. METHODS: We incubated human promyelocytic leukemia cell line
      HL60 cells with ethanol or aqueous extracts of the herb, and determined the
      levels of intracellular superoxide at 2 and 4 hours as well as caspase activity
      at 3, 6 and 8 hours using photospectrometry. Cancer cell survival and apoptosis
      were quantified at 24 hours by using MTT and flow cytometry analyses
      respectively. RESULTS: We found that it dose-dependently inhibited the cancer
      cell growth in MTT assay. Flow cytometry analysis revealed that it elicited
      significant production of sub-G(1) population of the cells, indicating the
      extract-evoked cell apoptotic death. The LD(50) of the ethanol extract was
      estimated to be approximately 320 microg/ml. Moreover, treatment of the cancer
      cells with the ethanol component markedly increased the production of superoxide
      within few hours. Significant elevation in the protease activities of caspases-2
      and -3 were detected at as early as 3 and 6 hours respectively. CONCLUSION: Our
      results show that the ethanol extract of the herb effectively evokes cancer cell
      apoptosis, possibly through burst-mediated caspase activation.

PMID- 16965743
TI  - [Effects of Runing Recipe medicated serum on expressions of genes in breast
      cancer cells].
AB  - OBJECTIVE: To explore the mechanisms of the effects of Runing Recipe in anti
      invasion and anti-recurrence of breast cancer by experimental research in vitro.
      METHODS: SD female rats were randomly divided into Runing Recipe-treated group
      and its decomposed formulas Kidney-Warming Recipe and Liver-Soothing Recipe
      treated groups, tamoxifen (TAM) -treated group, cyclophosphamide (CTX) -treated
      group, and normal control group to make medicated serums. Methods of matrigel
      basement membrane and real-time reverse transcription polymerase chain reaction
      were employed to investigate the gene expressions of vascular endothelial growth
      factor (VEGF), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of
      metalloproteinase-1 (TIMP-1) after MDA-MB-435 cells were treated with the
      medicated serums. RESULTS: The gene expression of VEGF was dropped in CTX
      treated, TAM-treated and Liver-Smoothing Recipe-treated groups. The gene
      expression of TIMP-1 was up-regulated in CTX-treated, Runing Recipe-treated and
      Kidney-Warming Recipe-treated groups; while MMP-9 was down-regulated in these
      groups. CONCLUSION: The mechanisms of Runing Recipe in inhibiting the cancer cell
      invasion may be related to down-regulating the gene expressions of VEGF and MMP
      9, and up-regulating the gene expression of TIMP-1.

PMID- 16965744
TI  - [Effects of Jianpi Yishen Recipe on recurrence, metastasis and life span of mice
      transplanted with proventriculus squamous carcinoma after tumorectomy].
AB  - OBJECTIVE: To observe the effects of Jianpi Yishen Recipe (JPYSR), a compound
      Chinese herbal medicine, on recurrence, metastasis and life span of mice
      transplanted with proventriculus squamous carcinoma cells after tumorectomy.
      METHODS: JPYSR was orally administered to 615 mice transplanted with
      proventriculus squamous carcinoma cells in the palma of left hind limb after
      tumorectomy. The local tumor recurrence, lung metastasis and life span of the
      mice were evaluated and compared with those of the 5-FU-treated mice and
      untreated mice. RESULTS: The pulmonary metastasis rate was 94.4% and the
      recurrence rate was 94.44% in untreated group. The pulmonary metastasis rate was
      68.4%, the inhibition rate of pulmonary metastasis was 27.5%, the recurrence rate
      was 78.95%, and the inhibition rate of tumor recurrence was 65.35% in JPYSR
      treated group. The average and median life spans were obviously prolonged in
      JPYSR-treated group, as compared with those in untreated group. The life
      prolonging rate was 100%. CONCLUSION: JPYSR can effectively inhibit the local
      recurrence and pulmonary metastasis of the transplanted proventriculus squamous
      carcinoma in mice after tumorectomy, and prolong the life span.

PMID- 16965745
TI  - [Effects of ethanol extracts of Panax notoginseng on liver metastasis of B16
      melanoma grafted in mice].
AB  - OBJECTIVE: To observe the effects of ethanol extracts of Panax notoginseng on the
      tumor and the liver metastasis in experimental mice grafted with B16 melanoma.
      METHODS: B16 melanoma was transplanted in the spleen of C57BL/6 mice. The effects
      of different doses of ethanol extracts of Panax notoginseng on the inhibition
      rate of spleen tumors and the liver metastasis were observed respectively.
      RESULTS: The high-, medium-, and low-doses of the extracts and the interferon
      alpha (IFN-alpha) can improve the quality of life of the experimental mice. The
      weights of spleen tumor were lower in the low- and medium-dose extracts-treated
      groups and the IFN-alpha-treated group than that in the normal saline (NS)
      treated group (P<0.05 or P<0.01). The liver metastasis was less in the low- and
      medium-dose extracts-treated groups and the IFN-alpha-treated group than that in
      the NS-treated group (P<0.01). CONCLUSION: The ethanol extracts of Panax
      notoginseng can improve the quality of life of the experimental mice and inhibit
      the growth of tumor and the liver metastasis.

PMID- 16965746
TI  - [Tumor inhibiting and immunoloregulation effects of Mylabris Mixture on H22
      cancer-bearing mice].
AB  - OBJECTIVE: To investigate the mechanisms of tumor inhibiting and
      immunoloregulation of Mylabris Mixture on H22 cancer-bearing mice. METHODS: H22
      cancer-bearing mice were chosen to observe the effects of tumor inhibiting and
      detect the proliferation function of T lymphocytes, the toxicity function of NK
      cells, the changes of T lymphocytes and the contents of interferon-gamma and
      interleukin-4. RESULTS: Mylabris Mixture could obviously inhibit the growth of
      H22 cancer in mice, and the tumor inhibition rat was 65.76%. The stimulation
      index of T lymphocyte transformation and percentage of NK cells in Mylabris
      Mixture-treated group were obviously higher than those in the normal control
      group. The subpopulation proportion of T lymphocytes in Mylabris Mixture-treated
      group was changed more than the normal control group. The production of
      interferon-gamma and interleukin-4 by T lymphocytes obviously increased in
      Mylabris Mixture-treated group (P<0.05, P<0.001). CONCLUSION: Mylabris Mixture
      has the effect of inhibiting the growth of tumor constitution, and regulating
      immunological function on mice with tumor. Its mechanisms include the
      reinforcement of T lymphocyte immune function, NK cell killing function and
      humoral immune function.

PMID- 16965747
TI  - [Effects of Qinggan Huoxue Recipe and its decomposed formulas on CD14, Toll like
      receptor 4 and nuclear factor-kappaB expressed by Kupffer cells].
AB  - OBJECTIVE: To investigate the effects of Qinggan Huoxue Recipe (QGHXR), a
      compound Chinese herbal medicine, and its decomposed formulas Qinggan Recipe
      (QGR) and Huoxue Recipe (HXR) on expressions of CD14, Toll like receptor 4
      (TLR(4)) and nuclear factor-kappaB (NF-kappaB) in Kupffer cells. METHODS: The
      isolated primary rat Kupffer cells were treated with lipopolysaccharide (LPS) for
      a certain period of time, a series of concentrations of drug-containing serums of
      QGHXR and its decomposed formulas were added, the expressions of NF-kappaB, tumor
      necrosis factor-alpha (TNF-alpha), CD14, and TLR(4) of the Kupffer cells were
      detected in different culture conditions by using Western blot, real-time reverse
      transcription polymerase chain reaction (RT-PCR) and ELISA methods respectively.
      RESULTS: QGR could down-regulate the expression of membrane receptor CD14, but
      the expression of NF-kappaB and TNF-alpha were not significantly decreased after
      QGR treatment. HXR could down-regulate the expression of membrane receptor TLR4
      and inhibit the expressions of NF-kappaB and TNF-alpha. QGHXR could down regulate
      the expressions of membrane receptors CD14 and TLR(4) and inhibit the expressions
      of NF-kappaB and TNF-alpha. CONCLUSION: QGHXR can protect liver cells by down
      regulating the expressions of CD14, TLR(4) and NF-kappaB and inhibiting TNF-alpha
      expression.

PMID- 16965748
TI  - [Effects of Cordyceps sinensis on dimethylnitrosamine-induced liver fibrosis in
      rats].
AB  - OBJECTIVE: To study the effects of Cordyceps sinensis on dimethylnitrosamine
      induced liver fibrosis in rats. METHODS: SD rats were divided into normal control
      group, untreated group and Cordyceps sinensis-treated group. The rats in each
      group were fed with corresponding drug for 4 weeks. The rat's liver collagen
      deposition was observed with collagen staining. Hydroxyproline (Hyp) contents in
      liver tissue of the rats in 3 groups were determined with HCl hydrolysis. The
      tissue inhibitor of metalloproteinase-2 (TIMP-2) and type IV collagen contents
      were observed by Envision, and matrix metalloproteinases-2 (MMP-2) activity was
      detected by the method of enzyme-picture. Type I collagen was detected by Western
      blotting. RESULTS: The contents of Hyp, TIMP-2, type IV collagen, and the
      expression of type I collagen in untreated group were significantly higher than
      those in the normal control group, while those in Cordyceps sinensis-treated
      group were significantly lower than those in the untreated group. The content of
      MMP-2 in untreated group was significantly lower than that in the normal control
      group, while that in Cordyceps sinensis-treated group was significantly higher
      than that in the untreated group. CONCLUSION: Cordyceps sinensis can considerably
      relieve the liver fibrosis, and the mechanism may be related to promoting the
      degradation of the collagens.

PMID- 16965749
TI  - [Effects of Shengqing Capsules on expression of nuclear factor-kappaB protein in
      liver cells of guinea pigs with pigment gallstone].
AB  - OBJECTIVE: To study the mechanisms of Shengqing Capsules, a compound Chinese
      herbal medicine for dispersing stagnated liver qi and promoting bile flow, in
      prevention and treatment of pigment gallstone. METHODS: Liver cells from guinea
      pigs with pigment gallstone were primarily cultured in vitro. The serums
      containing different concentrations of Shengqing Capsules were prepared by serum
      pharmacological method. The primary cultured hepatocytes with excessive
      expression of nuclear factor-kappaB (NF-kappaB) were stimulated with
      lipopolysaccharides (LPS) and the effects of the drug-containing serums on the NF
      kappaB expression were detected by Western-blotting. RESULTS: Shengqing Capsules
      down-regulated the NF-kappaB expression increased by LPS stimulation. The effect
      is dose-dependent. CONCLUSION: Shengqing Capsules can down-regulate the NF-kappaB
      expression increased by LPS stimulation. It may be one of the important
      mechanisms of this Chinese herbal medicine in prevention and treatment for
      pigment gallstone formation and the inflammatory reaction in biliary tract.

PMID- 16965750
TI  - [Effects of Guben Hutan Tongmai Recipe on expressions of macrophages and cell
      adhesion molecules of aortic endothelia in rats with syndrome of phlegm blocking
      blood vessel].
AB  - OBJECTIVE: To observe the effects of Guben Huatan Tongmai Recipe (GBHTTMR), a
      compound Chinese herbal recipe, on expressions of macrophages and cell adhesion
      molecules (CAMs) of aortic endothelia in rats with syndrome of phlegm blocking
      blood vessel, and to explore the pathogenesis of the phlegm-pathogen. METHODS:
      Fifty normal male Wistar rats, 7-week in age, were randomly divided into five
      groups: normal control group, untreated group, high-dose GBHTTMR-treated group,
      low-dose GBHTTMR-treated group and simvastatin-treated group, with 10 rats in
      each group. Syndrome of phlegm blocking blood vessel was induced in rats of the
      latter 4 groups by feeding the rats with high lipid diet. Levels of blood lipid
      were compared among the 5 groups. The expressions of macrophages and CAMs in
      aortic endothelia were tested by immunohistochemical staining method. RESULTS:
      The level of blood lipid, and the expressions of macrophages and CAMs showed
      statistical differences between the normal control group and the untreated group
      (P<0.01), and between the untreated group and the low-, high-dose GBHTTMR-treated
      and simvastatin-treated groups as well (P<0.05). CONCLUSIONS: GBHTTMR can
      decrease the level of serum cholesterol and triglycerides, and increase the level
      of high density lipoprotein. It also can inhibit the expressions of macrophages,
      intercellular adhesion molecule-1, vascular cell adhesion molecule-1, P-selectin,
      and E-selectin.

PMID- 16965751
TI  - [Protective effect of hyperin on focal cerebral ischemia reperfusion injury in
      rats].
AB  - OBJECTIVE: To investigate the protective effect of hyperin (Hyp) on focal
      cerebral ischemia reperfusion injury in rats. METHODS: Sixty Wistar male rats
      were randomly divided into sham-operated group, untreated group, and high-,
      medium- and low-dose Hyp-treated groups (50, 25 and 12.5 mg x kg(-1) x d(-1)) and
      ginkgo leaf-treated group. The animals were intragastrically administered with
      drugs for 5 days. Thirty minutes after the end administration, the operation was
      performed to induce the middle cerebral artery occlusion (MCAO) model in rats
      with the method of intraluminal thread. The middle cerebral artery blood flow was
      blocked for 2 hours, and then reperfused. Twenty-four hours later, the rats'
      neurology score was observed. Brain triphenyltetrazolium chloride (TTC) staining
      and dried wet method were carried out to measure the infarct size and the water
      content of rat brain tissue respectively. RESULTS: The above-mentioned indexes in
      the untreated group showed significant differences compared with those in the
      sham-operated group (P<0.01).The infarct sizes of rat brain tissue in the high-
      and medium-dose Hyp-treated groups were obviously decreased compared with that in
      the untreated group (P<0.01, P<0.05). The water content of rat brain and the
      neurology score were also obviously reduced compared with those in the untreated
      group (P<0.05 or P<0.01). CONCLUSIONS: Hyp could obviously reduce the brain
      infarct size and cerebral edema degree in focal cerebral ischemia reperfusion
      injury rats. Hyp has significant protective effect on focal cerebral ischemia
      reperfusion injury.

PMID- 16965752
TI  - [Effects of Naomaitong Recipe on expressions of nuclear factor-kappaB and nitric
      oxide synthases in brain tissue after focal cerebral ischemia reperfusion in aged
      rats].
AB  - OBJECTIVE: To study the effects of Naomaitong Recipe, a compound Chinese herbal
      medicine, on the expressions of nuclear factor-kappaB (NF-kappaB) and nitric
      oxide synthases (NOSs) in brain tissue after focal cerebral ischemia reperfusion
      in aged rats and the dosage-effect relationship. METHODS: We adopted the middle
      cerebral artery occlusion (MCAO) in aged rats as the focal cerebral ischemia
      model, with 3-hour ischemia and 12-day reperfusion, and observed the changes of
      the nerve dysfunction score, the water content of cerebral constitution and the
      expressions of NF-kappaB, heat-shock protein 70 (HSP70) and NOSs in cerebral
      cortex. RESULTS: The nerve dysfunction score, the water content of cerebral
      constitution, the expressions of NF-kappaB, HSP70, neuronal nitric-oxide synthase
      (nNOS), endothelial nitric-oxide synthase (eNOS) and inducible nitric-oxide
      synthase (iNOS) in the untreated group were higher than those of the sham
      operated group. The nerve dysfunction score, the water content of cerebral
      constitution, the expressions of NF-kappaB, iNOS and nNOS were lower, while the
      expressions of HSP70 and eNOS were higher in the high-, medium- and low-dose
      Naomaitong-treated groups and nimodipine-treated group than those of the
      untreated-group. The nerve dysfunction score and the expression of nNOS were
      lower, while the expression of eNOS was higher in the medium-dose Naomaitong
      treated group than those of the nimodipine-treated group. The expressions of
      HSP70 and eNOS were higher, while the other indices were lower in the medium-dose
      Naomaitong-treated group than those of the low-dose Naomaitong-treated group.
      CONCLUSION: Naomaitong Recipe can protect the brain cells from damage after focal
      cerebral ischemia reperfusion injury by adjusting the expressions of NF-kappaB,
      HSP70 and NOSs, and the medium-dose Naomaitong Recipe is more effective.

PMID- 16965753
TI  - [Laser lithotripsy under choledochoscope combined with Yiqi Rougan Recipe in
      treatment of multiple hepatolithus].

PMID- 16965754
TI  - [Diagnoses and treatment of 125 patients with biliary acute pancreatitis].

PMID- 16965755
TI  - [Clinical observation of Zhuhuang Decoction in ovulation induction].

PMID- 16965756
TI  - [Status and progress of application of Chinese herbs in sports medicine].

PMID- 16965757
TI  - [Comments on some issues concerning the English translation of traditional
      Chinese medicine].

PMID- 16965758
TI  - [Review and reflection on history of English translation of traditional Chinese
      medicine].

PMID- 16965759
TI  - Using surface plasmon resonance to directly measure slow binding of low-molecular
      mass inhibitors to a VanX chip.
AB  - VanX, a d,d-dipeptidase, is one of five gene products responsible for vancomycin
      resistance in pathogenic bacteria and is an attractive drug target in
      circumventing clinical drug resistance. Our previous combinatorial search of VanX
      substrates in a dipeptide library of d-X(1)-d-X(2) (19(2)=361) forms has led to
      the discovery of three new compounds (d-Ala-d-Phe, d-Ala-d-Tyr, and d-Ala-d-Trp)
      having higher k(cat)/K(M) values than those of its natural substrate, d-Ala-d
      Ala. Based on structures of newly identified substrates, two representative
      transition state analogs of substrates, d-Ala(P,O)d-Phe (6a) and d-Ala(P,O)d-Ala
      (6b) dipeptide phosphonates, used as VanX inhibitor were rationally designed and
      chemically synthesized. In the synthesis, eight synthetic steps in total were
      employed for preparing each VanX inhibitor, and their overall isolated yields
      were 21 and 11% for 6a and 6b, respectively. Binding interactions of d-Ala(P,O)d
      Phe (6a) and d-Ala(P,O)d-Ala (6b) with VanX were confirmed unambiguously and
      measured quantitatively by surface plasmon resonance. The result reveals that
      both dipeptide phosphonates are slow-binding inhibitors of VanX (for 6a,
      k(on)=1.18 x 10(3)M(-1)s(-1), k(off)=2.31 x 10(-3) s(-1), K(D)=1.96 microM,
      chi(2)=0.0737; for 6b, k(on)=1.09 x 10(3)M(-1)s(-1), k(off)=1.80 x 10(-2)s(-1),
      K(D)=16.5 microM, chi(2)=0.0599). This suggests that only a fraction of the
      conformers of the inhibitors in solution adopts a conformation best suited for
      binding interaction with VanX and that the VanX-inhibitor complex may
      concomitantly undergo a conformational isomerization from an initial but fast
      weak-binding adduct to slowly convert to a tight-binding complex with a more
      stable bound geometry. Moreover, in comparison with 6b, an additional aromatic
      interaction of 6a with the Phe79 residue in the active site of the enzyme,
      through an energetically favorable face-to-face offset stacked orientation, may
      account for its higher affinity than 6b to VanX.

PMID- 16965760
TI  - D-myo-inositol 1-phosphate as a surrogate of D-myo-inositol 1,4,5-tris phosphate
      to monitor G protein-coupled receptor activation.
AB  - Phospholipase C beta (PLC-beta)-coupled G protein-coupled receptor (GPCR)
      activities traditionally are assessed by measuring Ca2+ triggered by D-myo
      inositol 1,4,5-trisphosphate (IP3), a PLC-beta hydrolysis product, or by
      measuring the production of inositol phosphate using cumbersome radioactive
      assays. A specific detection of IP3 production was also established using IP3
      binding proteins. The short lifetime of IP3 makes this detection very challenging
      in measuring GPCR responses. Indeed, this IP3 rapidly enters the metabolic
      inositol phosphate cascade. It has been known for decades that lithium chloride
      (LiCl) leads to D-myo-inositol 1-phosphate accumulation on GPCR activation by
      inhibiting inositol monophosphatase, the final enzyme of the IP3 metabolic
      cascade. We show here that IP1 can be used as a surrogate of IP3 to monitor GPCR
      activation. We developed a novel homogeneous time-resolved fluorescence (HTRF)
      assay that correlates perfectly with existing methods and is easily amenable to
      high-throughput screening. The IP-One assay was validated on various GPCR models.
      It has the advantage over the traditional Ca2+ assay of allowing the measurement
      of inverse agonist activity as well as the analysis of PLC-beta activity in any
      nontransfected primary cultures. Finally, the high assay specificity for D-myo
      inositol 1 monophosphate (IP1(1)) opens new possibilities in developing selective
      assays to study the functional roles of the various isoforms of inositol
      phosphates.

PMID- 16965761
TI  - Length-dependence of flexural rigidity as a result of anisotropic elastic
      properties of microtubules.
AB  - Unexplained length-dependence of flexural rigidity and Young's modulus of
      microtubules is studied using an orthotropic elastic shell model. It is showed
      that vibration frequencies and buckling load predicted by the accurate
      orthotropic shell model are much lower than that given by the approximate
      isotropic beam model for shorter microtubules, although the two models give
      almost identical results for sufficiently long microtubules. It is this
      inaccuracy of the isotropic beam model used by all previous researchers that
      leads to reported lower flexural rigidity and Young's modulus for shorter
      microtubules. In particular, much lower shear modulus and circumferential Young's
      modulus, which only weaken flexural rigidity of shorter microtubules, are
      responsible for the observed length-dependence of the flexural rigidity. These
      results confirm that longitudinal Young's modulus of microtubules is length
      independent, and the observed length-dependence of the flexural rigidity and
      Young's modulus is a result of strongly anisotropic elastic properties of
      microtubules which have a length-dependent weakening effect on flexural rigidity
      of shorter microtubules.

PMID- 16965762
TI  - Chondroitinase ABC promotes axonal re-growth and behavior recovery in spinal cord
      injury.
AB  - In spinal cord injury, the injury could trigger some inhibitory signal cascades
      to promote chondroitin sulfate proteoglycans (CSPGs), the structures of scar
      tissues, formation. CSPGs could limit axonal regeneration mainly through the
      glycosaminoglycan (GAG) chain in the lesion site were suggested. We hypothesized
      that the digestion of CSPGs by chondroitinase ABC (ChABC) might decrease the
      inhibitory effects of limiting axonal re-growth after spinal cord injury. We
      compared the digesting products of CSPGs such as 2B6 by ChABC with the untreated
      control group and found no immunostaining of 2B6 in control group. The smaller
      size scars of ChABC-treatment were observed via CS-56, a type of CSPGs, 8 weeks
      after transection by immunohistochemistry. The inhibitory effects of CSPGs
      withdraw GAGs following ChABC-treatment would reduce, and immunopositive GAP-43
      newly outgrown fibers were identified. In the animal trials, ChABC-treatment
      could improve motor function through BBB locomotor's test and reduce limiting
      ability of scar tissues to promote axonal regeneration via changing the structure
      of CSPGs by immunohistochemistry with GAP-43.

PMID- 16965763
TI  - Effect of F-spondin on cementoblastic differentiation of human periodontal
      ligament cells.
AB  - Cementum is a mineralized tissue produced by cementoblasts covering the roots of
      teeth that provides for the attachment of periodontal ligament to roots and
      surrounding alveolar bone. To study the mechanism of proliferation and
      differentiation of cementoblasts is important for understanding periodontal
      physiology and pathology including periodontal tissue regeneration. However, the
      detailed mechanism of the proliferation and differentiation of human
      cementoblasts is still unclear. We previously established human cementoblast-like
      (HCEM) cell lines. We thought that comparing the transcriptional profiles of HCEM
      cells and human periodontal ligament (HPL) cells derived from the same teeth
      could be a good approach to identify genes that influence the nature of
      cementoblasts. We identified F-spondin as the gene demonstrating the high fold
      change expression in HCEM cells. Interestingly, F-spondin highly expressing HPL
      cells showed similar phenotype of cementoblasts, such as up-regulation of
      mineralized-related genes. Overall, we identified F-spondin as a promoting factor
      for cementoblastic differentiation.

PMID- 16965764
TI  - NF-kappaB and inflammation in genetic disease.
AB  - By responding to pro-inflammatory cytokines, such as IL-1beta and TNF-alpha, and
      controlling itself the expression of numerous mediators of inflammation, NF
      kappaB plays a pivotal role in controlling the proper sequence of events
      characterizing the inflammation process. Although excessive NF-kappaB activation
      is often associated with inflammatory signs in many different tissues, impaired
      NF-kappaB activation can also generate inflammation. This is the case in humans
      suffering from the genetic disease incontinentia pigmenti that exhibit severe
      skin inflammation. Identifying the molecular basis of this pathology, mutations
      affecting the gene coding for NEMO, has allowed production of mouse models for
      investigating the disease. Their characterization supports the view that a very
      tight positive and negative regulation of the NF-kappaB signaling pathway is
      required in vivo to ensure not only a fine-tuned response to injury or infection
      but also to maintain tissue homeostasis.

PMID- 16965765
TI  - NF-kappaB activation by double-strand breaks.
AB  - Cellular response to DNA damage is complex and relies on the simultaneous
      activation of different networks. It involves DNA damage recognition, repair, and
      induction of signalling cascades leading to cell cycle checkpoint activation,
      apoptosis, and stress related responses. The fate of damaged cells depends on the
      balance between pro- and antiapoptotic signals. In this decisive life or death
      choice, the transcription factor NF-kappaB has emerged as a prosurvival actor in
      most cell types. As corollary, it appears to be associated with tumorigenic
      process and resistance to therapeutic strategies as it protects cancerous cells
      from death. In this review, we will focus on NF-kappaB activation by double
      strand breaks inducing agents, such as ionizing radiation and DNA topoisomerase I
      and II inhibitors routinely used in cancer therapy. Coinciding with the 20th
      anniversary of the NF-kappaB discovery, major steps of the DSB-triggered cascade
      have been recently identified. Two parallel cascades are necessary for NF-kappaB
      activation. The first one depends on ATM (activated by double-strand breaks) and
      the second on PIDD (activated by an unknown stress signal). The phosphorylation
      of NEMO by ATM is the point of convergence of these two cascades. The
      identification of ATM/NEMO complex as the long searched "nuclear to cytoplasm"
      signal leading to IKK activation is also a major piece of the puzzle. The
      knowledge of the precise steps leading to DSB-initiated NF-kappaB activation will
      allow the development of specific blocking compounds reducing its prosurvival
      function.

PMID- 16965766
TI  - Human equilibrative nucleoside transporter-1 (hENT1) is required for the
      transcriptomic response of the nucleoside-derived drug 5'-DFUR in breast cancer
      MCF7 cells.
AB  - Nucleoside analogues are broadly used in cancer treatment. Although nucleoside
      metabolism is a necessary step in the development of their cytotoxicity, mediated
      transport across the plasma membrane might be needed for nucleoside-derived drugs
      to exert their pharmacological action. In this study, we have addressed the
      question of whether particular plasma membrane transporters contribute to the
      transcriptomic response associated with nucleoside-derived drug therapy. Firstly,
      we have characterized the nucleoside transporters responsible for 5'-DFUR uptake
      into the breast cancer cell line MCF7. 5'-DFUR is the immediate precursor of 5-FU
      and a metabolite of the orally administered pro-drug capecitabine, currently used
      in the treatment of breast cancer and other solid tumors. Although 5'-DFUR is a
      substrate for both plasma membrane equilibrative nucleoside carriers, hENT1 shows
      higher affinity for this molecule than hENT2. Inhibition of hENT1 function
      partially protected MCF7 cells from 5'-DFUR-induced cytotoxicity. Secondly, we
      have used a pharmacogenomic approach to determine how inhibition of hENT1
      function contributes to the transcriptomic response associated to 5'-DFUR
      treatment. Under hENT1 inhibition most of the transcriptional targets of 5'-DFUR
      action, which were genes associated with apoptosis and cell cycle progression
      were blocked. This study demonstrates that although 5'-DFUR is substrate for both
      equilibrative nucleoside carriers, hENT1 function is essential for the full
      transcriptional response to 5'-DFUR treatment.

PMID- 16965767
TI  - Diphenyl diselenide reduces temporarily hyperglycemia: possible relationship with
      oxidative stress.
AB  - This study was designed to determine the effect of diphenyl diselenide and
      ebselen, synthetic organoselenium compounds with antioxidant properties, in
      diabetic rats. Diabetes was induced by the administration of streptozotocin (STZ)
      (45mg/kg, intravenous). In experimental trials, diphenyl diselenide, but not
      ebselen, caused a significant reduction in blood glucose levels of STZ-treated
      rats. This effect of diphenyl diselenide was accompanied by a reduction in the
      levels of glycated proteins. Diphenyl diselenide ameliorate superoxide dismutase
      activity (liver and erythrocytes) and Vitamin C levels (liver, kidney and blood),
      which were decreased in STZ-treated rats. In normal rats, diphenyl diselenide
      caused per se an increase in hepatic, renal and blood GSH levels. Similarly,
      treatment with diphenyl diselenide restored hepatic and renal GSH levels in STZ
      treated rats. TBARS and protein carbonyl levels were not modified by STZ and/or
      diphenyl diselenide and ebselen treatments. Our findings suggest that diphenyl
      diselenide can be considered an anti-diabetogenic agent by exhibiting anti
      hyperglycemic and antioxidant properties.

PMID- 16965769
TI  - Mechanisms of cell death of neural progenitor cells caused by trophic support
      deprivation.
AB  - Cell death of neural progenitor cells is the primary problem limiting the value
      of neural progenitor cell-based therapy for central nervous system disorders.
      However, little is known about the mechanism of cell death of neural progenitor
      cells. In this study, we investigated the mechanisms of cell death of a
      multipotent cell line, MEB5, caused by deprivation of epidermal growth factor
      (EGF). When EGF was removed from the culture medium, the total number of viable
      MEB5 cells reduced, and nuclear condensation and elevation of caspase-3-like
      enzyme activity were observed in MEB5 cells. Treatment with a broad-range caspase
      inhibitor reduced cell death in a concentration-dependent manner, indicating that
      MEB5 cells undergo caspase-mediated apoptotic cell death caused by EGF
      deprivation. We also investigated the effects of glutamate receptor antagonists,
      antioxidants and nitric oxide synthase inhibitor on EGF deprivation-induced cell
      death. N-methyl-D-aspartate (NMDA) glutamate receptor antagonists, alpha-amino-3
      hydrozy-5-methyl-4-isoxazole propionic acid (AMPA) glutamate receptor antagonist
      and nitric oxide synthase inhibitor failed to reduce cell death. In contrast, two
      antioxidants with different chemical structures reduced cell death in a
      concentration-dependent manner. The production of reactive oxygen species was
      detected in MEB5 cells after EGF deprivation by monitoring
      dichlorodihydrofluorescein fluorescence as a marker of reactive oxygen species
      related radicals. Our results suggest that oxidative stress triggers caspase
      mediated apoptosis of neural progenitor cells by trophic support deprivation.

PMID- 16965770
TI  - PTH-related protein upregulates integrin alpha6beta4 expression and activates Akt
      in breast cancer cells.
AB  - Breast cancer is the most common carcinoma that metastasizes to bone. Tumor
      produced parathyroid hormone-related protein (PTHrP), a known stimulator of
      osteoclastic bone resorption, is a major mediator of the osteolytic process in
      breast cancer. We have previously shown that PTHrP increases breast cancer cell
      proliferation, survival, migration, and pro-invasive integrin alpha6beta4
      expression. To determine the role of integrin alpha6beta4 in these PTHrP-mediated
      effects, we utilized two strategies to modulate expression of the alpha6 and
      beta4 subunits in parental and PTHrP-overexpressing MDA-MB-231 and MCF-7 cells:
      overexpression of alpha6beta4 by transfection with constructs encoding the alpha6
      and beta4 subunits, and suppression of endogenous alpha6beta4 expression by
      transfection with siRNAs targeting these subunits. We now show that the effects
      of PTHrP are mediated via upregulation of integrin alpha6beta4 expression. We
      also show that integrin alpha6beta4 expression is modulated at the mRNA level,
      indicating a transcriptional and/or post-transcriptional mechanism of action for
      PTHrP. PTHrP expression also increased the levels of phosphorylated Akt, with a
      consequent increase in the levels of phosphorylated (inactive) glycogen synthase
      kinase-3 (GSK-3). The role of PTHrP in breast cancer growth and metastasis may
      thus be mediated via upregulation of integrin alpha6beta4 expression and Akt
      activation, with consequent inactivation of GSK-3.

PMID- 16965771
TI  - Effects of the COOH-terminal tripeptide alpha-MSH(11-13) on corneal epithelial
      wound healing: role of nitric oxide.
AB  - It is known that alpha-melanocyte stimulating hormone (alpha-MSH) may exert anti
      inflammatory effects and facilitate reparative processes in different tissues.
      The effective message sequence of alpha-MSH resides in the COOH-terminal
      tripeptide alpha-MSH(11-13). This study was undertaken to investigate the effects
      of topical administration of the COOH-terminal tripeptide sequence of alpha-MSH
      (alpha-MSH(11-13), KPV) on corneal epithelial wound healing in rabbits and the
      possible role of nitric oxide (NO) in these effects. The whole corneal epithelium
      was denuded in both eyes by mechanical abrasion. The area of the corneal
      epithelial defect was stained with fluorescein, photographed, and then measured
      before the treatment and every 12 h by a computerized software. The mean
      epithelial wound area and the mean percent of epithelial defect remaining at each
      follow-up control were compared between experimental groups. Rabbits were
      topically treated with KPV 1, 5 or 10 mg/ml (30 microl), two drops four times in
      a day, for 4 days, starting immediately after corneal abrasion, while control
      animals received topical phosphate-buffered saline as vehicle. In order to study
      the role of NO in corneal repair processes, the NO donor, sodium nitroprusside
      (SP, 10 mg/ml, 30 microl) was administered in both eyes, two drops four times in
      a day, for 4 days. The effects of KPV or SP were challenged by pre-treatment with
      the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L
      NAME, 10 mg/ml, 30 microl) 30 min prior to KPV or SP instillation. The mean
      percent epithelial defect remaining each time was significantly smaller in
      animals treated with KPV or SP in comparison to controls. Sixty hours later,
      eight out of eight (100%) corneas treated with KPV or SP were completely re
      epithelized (P<0.05) while none of the corneas treated with placebo were re
      epithelized. Pre-treatment with L-NAME inhibited the facilitating effect of KPV
      on corneal epithelial wound healing process and totally prevented the effect of
      SP. Rabbit corneal epithelial cells (RCE) in culture were exposed for 1, 6 and 24
      h to different KPV concentrations (0.1, 1 and 10 microM) in medium containing 15%
      foetal bovine serum (FBS). Cell viability was stimulated by 1 and 10 microM
      concentrations of the substance. Thus, KPV may facilitate corneal epithelial
      wound healing in rabbits with a mechanism that may involve NO disposition in
      corneal tissue. However, it is not known whether this mechanism is likely to
      depend on a direct stimulating repairing activity shared by the entire molecule
      of alpha-MSH.

PMID- 16965772
TI  - Effect of GLC756, a novel mixed dopamine D1 receptor antagonist and dopamine D2
      receptor agonist, on TNF-alpha release in vitro from activated rat mast cells.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is released from activated mast cells via
      an IgE-dependent mechanisms, and plays a crucial role in ocular allergic
      inflammation. This study examined the influence of three antiglaucoma drugs
      differing in their chemical structure and pharmacological profile (i.e.
      latanoprost, timolol, GLC756) on TNF-alpha release from activated rat mast cells.
      A rat basophilic leukemia mast cell line (RBL-2H3) was activated via IgE/anti
      IgE. Rat mast cells were incubated with latanoprost, timolol, GLC756 or
      betamethasone (positive control) at concentrations of 0.1, 1, 10 and 30 microM.
      TNF-alpha concentration in supernatant was measured by ELISA 5 h post-activation.
      Compared to controls, the prostaglandin derivative latanoprost and the beta
      blocker timolol in the concentration range 0.1-30 microM, had no significant
      effect on TNF-alpha release from rat mast cells measured 5h after activation. By
      contrast, the dopaminergic drug GLC756 compared to controls in the concentration
      range 1-30 microM significantly inhibited TNF-alpha release from activated rat
      mast cells in a concentration-dependent manner. The positive control
      betamethasone inhibited TNF-alpha release almost completely at all concentrations
      tested. In conclusion, the results of this study suggest that latanoprost and
      timolol do not reduce inflammation triggered by activated mast cells. By
      contrast, the dopaminergic drug GLC756 inhibited TNF-alpha release from activated
      mast cells, suggesting an palliative potential of dopaminergic compounds on
      allergic conjunctivitis in topical glaucoma medication.

PMID- 16965768
TI  - A genomic view of the sea urchin nervous system.
AB  - The sequencing of the Strongylocentrotus purpuratus genome provides a unique
      opportunity to investigate the function and evolution of neural genes. The
      neurobiology of sea urchins is of particular interest because they have a close
      phylogenetic relationship with chordates, yet a distinctive pentaradiate body
      plan and unusual neural organization. Orthologues of transcription factors that
      regulate neurogenesis in other animals have been identified and several are
      expressed in neurogenic domains before gastrulation indicating that they may
      operate near the top of a conserved neural gene regulatory network. A family of
      genes encoding voltage-gated ion channels is present but, surprisingly, genes
      encoding gap junction proteins (connexins and pannexins) appear to be absent.
      Genes required for synapse formation and function have been identified and genes
      for synthesis and transport of neurotransmitters are present. There is a large
      family of G-protein-coupled receptors, including 874 rhodopsin-type receptors, 28
      metabotropic glutamate-like receptors and a remarkably expanded group of 161
      secretin receptor-like proteins. Absence of cannabinoid, lysophospholipid and
      melanocortin receptors indicates that this group may be unique to chordates.
      There are at least 37 putative G-protein-coupled peptide receptors and precursors
      for several neuropeptides and peptide hormones have been identified, including
      SALMFamides, NGFFFamide, a vasotocin-like peptide, glycoprotein hormones and
      insulin/insulin-like growth factors. Identification of a neurotrophin-like gene
      and Trk receptor in sea urchin indicates that this neural signaling system is not
      unique to chordates. Several hundred chemoreceptor genes have been predicted
      using several approaches, a number similar to that for other animals.
      Intriguingly, genes encoding homologues of rhodopsin, Pax6 and several other key
      mammalian retinal transcription factors are expressed in tube feet, suggesting
      tube feet function as photosensory organs. Analysis of the sea urchin genome
      presents a unique perspective on the evolutionary history of deuterostome nervous
      systems and reveals new approaches to investigate the development and
      neurobiology of sea urchins.

PMID- 16965773
TI  - Late effects of enriched environment (EE) plus multimodal early onset stimulation
      (MEOS) after traumatic brain injury in rats: Ongoing improvement of neuromotor
      function despite sustained volume of the CNS lesion.
AB  - Recently we showed that the combination between MEOS and EE applied to rats for 7
      15 days after traumatic brain injury (TBI) was associated with reduced CNS lesion
      volume and enhanced reversal of neuromotor dysfunction. In a continuation of this
      work, we tested whether these effects persisted for longer post-operative
      periods, e.g. 30 days post-injury (dpi). Rats were subjected to lateral fluid
      percussion (LFP) or to sham injury. After LFP, one third of the animals (injured
      and sham) was placed under conditions of standard housing (SH), one third was
      kept in EE-only, and one third received EE+MEOS. Standardized composite
      neuroscore (NS) for neurological functions and computerized analysis of the
      vibrissal motor performance were used to assess post-traumatic neuromotor
      deficits. These were followed by evaluation of the cortical lesion volume (CLV)
      after immunostaining for neuron-specific enolase, caspase 3 active, and GFAP.
      Finally, the volume of cortical lesion containing regeneration-associated
      proteins (CLV-RAP) was determined in sections stained for GAP-43, MAP2, and
      neuronal class III beta-tubulin. We found (i) no differences in the vibrissal
      motor performance; (ii) EE+MEOS rats performed significantly better than SH rats
      in NS; (iii) EE-only and EE+MEOS animals, but not SH rats, showed better recovery
      at 30 dpi than at 15 dpi; (iv) no differences among all groups in CLV (larger
      than that at 15 dpi) and CLV-RAP, despite a clear tendency to reduction in the EE
      only and EE+MEOS rats. We conclude that EE+MEOS retards, but cannot prevent the
      increase of lesion volume. This retardation is sufficient for a continuous
      restoration of neurological functions.

PMID- 16965774
TI  - High prevalence of major cardiovascular risk factors in first-degree relatives of
      individuals with familial premature coronary artery disease--the GENECARD
      project.
AB  - BACKGROUND: Hypertension, hypercholesterolemia, obesity and smoking are highly
      prevalent among patients with familial premature coronary artery disease (FP
      CAD). Whether these risk factors equally affect other family members remains
      unknown. METHODS: We examined 222 FP-CAD patients, 158 unaffected sibs, 197
      offspring and 94 spouses in 108 FP-CAD families (> or = 2 sibs having survived
      CAD diagnosed before age 51 (M)/56 (F)), and compared them to population
      controls. RESULTS: Unaffected sibs had a higher prevalence of hypertension (49%
      versus 24%, p<0.001), hypercholesterolemia (47% versus 34%, p=0.002), abdominal
      obesity (35% versus 24%, p=0.006) and smoking (39% versus 24%, p=0.001) than
      population controls. Offspring had a higher prevalence of hypertension (females),
      hypercholesterolemia and abdominal obesity than population controls. No
      difference was observed between spouses and controls. Compared to unaffected
      sibs, FP-CAD affected sibs had a similar risk factor profile, except for smoking,
      which was more prevalent (76% versus 39%, p=0.008). CONCLUSIONS: Hypertension,
      obesity and hypercholesterolemia are highly prevalent among first-degree
      relatives, but not spouses, of patients with FP-CAD. These persons deserve
      special medical attention due to their familial/genetic susceptibility to
      atherogenic metabolic abnormalities. In these families, smoking may be the
      trigger for FP-CAD.

PMID- 16965775
TI  - QTL-specific genotype-by-smoking interaction and burden of calcified coronary
      atherosclerosis: the NHLBI Family Heart Study.
AB  - BACKGROUND: Calcified coronary plaque (CCP) is a complex trait influenced by both
      genes and environment, and plausibly an interaction between the two. Because the
      familial aggregation of CCP has been demonstrated and smoking is a significant,
      independent predictor of CCP, we assessed the evidence for genotype-by-smoking
      interaction and conducted linkage analysis of quantitative Agatston CCP scores in
      participants of the NHLBI Family Heart Study (FHS). METHODS: During standardized
      clinical exams smoking habits were ascertained and CCP was quantified with
      cardiac computed tomography (CT). Among 4387 relationship pairs from 2128
      Caucasian examinees variance component analysis was implemented in SOLAR to
      examine: (1) additive genotype-by-smoking status interaction using a variance
      component approach; (2) linkage analysis in the full sample and among smoking
      subsets defined by individual smoking exposure; (3) QTL-specific genotype-by
      smoking interaction in the regions that appeared to differentiate between smoking
      strata. RESULTS: The prevalence of CCP (and median Agatston score) was 75%
      (184.6) in men and 48% (51.0) in women. We detected four genome-wide significant
      logarithm of odds (LOD) scores in samples stratified by individual smoking
      exposure: chromosome 4 at 122cM (nearest marker D4S2297; robust adjusted LOD=3.1;
      q=0.053), chromosome 6 at 99cM (nearest marker D6S1056; robust adjusted LOD=3.3;
      q=0.053), chromosome 11 at 19cM (nearest marker D11S199; robust adjusted LOD=4.0;
      q=0.02) and chromosome 13 at 77cM (nearest marker D13S892; robust adjusted
      LOD=3.1; q=0.053). Additive and QTL-specific genotype-by-smoking interaction was
      detected on chromosomes 4, 6, 11 and 13; all P<0.05. Three of the four QTLs
      identified in this report have been previously linked to atherosclerosis and
      harbor interesting candidate genes. CONCLUSIONS: These findings demonstrate the
      importance of considering complex interactions in the search for genes that
      influence the pathogenesis of CCP.

PMID- 16965776
TI  - Combined therapy with ramipril and simvastatin has beneficial additive effects on
      tissue factor activity and prothrombin fragment 1+2 in patients with type 2
      diabetes.
AB  - Tissue factor (TF) plays a pivotal role in thrombus formation. Statins and
      angiotensin converting enzyme inhibitors attenuate expression of TF by distinct
      mechanism. Therefore, we hypothesized that combined therapy with simvastatin and
      ramipril may have additive beneficial anti-atherogenic effects to lower TF
      activity when compared with either drug alone. This was a randomized, double
      blind, placebo-controlled cross-over trial with three treatment arms (each 2
      months) and two washout periods (each 2 months). Fifty patients with type 2
      diabetes were given simvastatin 20 mg and placebo, simvastatin 20 mg and ramipril
      10 mg, or ramipril 10 mg and placebo daily during each treatment period.
      Simvastatin and ramipril monotherapy tended to reduce TF activity (0.53 to 0.46
      nM, P=0.056; 0.54 to 0.50 nM, P=0.167, respectively) while combined therapy had a
      significant effect (0.64 to 0.43 nM, P<0.001). All three therapies significantly
      reduced prothrombin fragment 1+2 (F1+2) levels from their respective baselines
      (P=0.037, P<0.001, and P=0.057, respectively). Combined therapy significantly
      reduced TF activity and F1+2 levels to a greater extent than either simvastatin
      or ramipril alone (P=0.029 and P=0.040 by ANOVA, respectively). Percent changes
      in TF activity and percent changes in F1+2 levels were significantly correlated.
      All three therapies reduced CD40 ligand levels from their respective baselines
      (P=0.098, P<0.001, and P=0.002, respectively) with no significant differences
      among these three therapies (P=0.204 by ANOVA). Ramipril combined with
      simvastatin significantly reduces plasma TF activity and F1+2 levels to a greater
      extent than monotherapy with either drug in patients with type 2 diabetes.

PMID- 16965777
TI  - Solid phase microextraction-gas chromatographic-mass spectrometric determination
      of nitrous oxide evolution to measure denitrification in estuarine soils and
      sediments.
AB  - A SPME-GC-MS method was developed to quantify nitrous oxide (N(2)O) to evaluate
      denitrification rates. There is a need for this sensitive and definitive N(2)O
      detection method to accurately measure the soil and sediment ability to convert
      anthropogenic mineral nitrogen loads to N(2) through denitrification hence
      decreasing estuarine waterway pollution loading. This method is applied to
      measure denitrification, which is a major pathway for inorganic nitrogen removal,
      by incorporating the acetylene (C(2)H(2)) block method on anaerobic assays.
      Currently, denitrification is largely measured using GCs fitted with TCD or ECD
      detectors. With a mean R(2) value of 0.996, the calibration curve spanned over
      three orders of magnitude (4.1-2030 nM) with a limit of detection (LOD) of 4.1 nM
      N(2)O (18 ppb) and a limit of quantification (LOQ) of 16 nM N(2)O (72 ppb). This
      detection method was valid with less than 15% relative standard deviation (RSD)
      and error for middle and high quality control (QC) points and less than 20% for
      low QC points on three experimental days. Measuring N(2)O using SPME-GC-MS
      technology allows for confidence in identification, high sensitivity,
      reproducibility, and short run times.

PMID- 16965778
TI  - Analysis of cytokinin nucleotides in coconut (Cocos nucifera L.) water using
      capillary zone electrophoresis-tandem mass spectrometry after solid-phase
      extraction.
AB  - A method based on solid-phase extraction (SPE) and capillary zone electrophoresis
      tandem mass spectrometry (CZE-MS/MS) is described for the separation and
      determination of six cytokinin nucleotides in coconut water. The best CZE
      separation for the six cytokinin nucleotide standards was achieved using a 25 mM
      ammonium formate/formic acid buffer (pH 3.8) and 2% (v/v) methanol with an
      applied gradient separation voltage (25 kV for 32 min, and then a linear gradient
      to 30 kV in 5 min, finally 30 kV to the end of separation) in less than 60 min.
      MS/MS with multiple reaction monitoring (MRM) detection was carried out to obtain
      sufficient selectivity and sensitivity for the cytokinin nucleotides. The
      combined use of on-line sample stacking and CZE-MS/MS achieved limits of
      detection (LODs) in the range of 0.06-0.19 microM for the six cytokinin
      nucleotides at a signal-to-noise ratio of 3. Furthermore, a novel dual-step SPE
      procedure was developed for the pre-concentration and purification of cytokinin
      nucleotides using Oasis HLB and Oasis MAX cartridges. The recoveries of the
      cytokinin nucleotides after the dual-step SPE were in the range of 44-71%. The
      combination of off-line SPE, on-line sample stacking and CZE-MS/MS approach was
      successfully applied to screen for endogenous cytokinin nucleotides present in
      coconut water sample. trans-Zeatin riboside-5'-monophosphate (ZMP) was detected
      and quantified in coconut water by CZE-MS/MS after SPE and on-line sample
      stacking.

PMID- 16965779
TI  - Determination of polybrominated diphenyl ethers at trace levels in environmental
      waters using hollow-fiber microporous membrane liquid-liquid extraction and gas
      chromatography-mass spectrometry.
AB  - In this study, we present a simple and easy-to-use extraction method that is
      based on a hollow-fiber microporous membrane liquid-liquid extraction (HF-MMLLE),
      as an extraction technique, followed by gas chromatography-mass spectrometry (GC
      MS) to determine a group of brominated flame retardants (BFRs), polybrominated
      diphenyl ethers (PBDEs), at trace levels in aqueous samples. The hollow-fiber
      membrane (HF) filled with organic solvent was immersed into the aqueous sample,
      spiked with the analytes at ng l(-1) level, and stirred for 60 min. The proposed
      method could attain enrichment factors (E(e)) up to 5200 times, after optimising
      parameters, such as organic solvent, stirring speed and extraction time, that
      affect the extraction. The HF-MMLLE-GC-MS method was successfully applied to the
      extraction of PBDEs from tap, river and leachate water samples with spike
      recoveries ranging from 85% to 110%. The method validation with reagent and
      leachate water samples provided good linearity, detection limits of 1.1 ng l(-1)
      or lower, both in reagent and leachate water, as well as satisfactory precision
      in terms of repeatability and reproducibility with values of % relative standard
      deviation (%RSD) lower than 8.6 and 16.9, respectively.

PMID- 16965780
TI  - Determination of the binding parameters for antithrombin-heparin fragment systems
      by affinity and frontal analysis continuous capillary electrophoresis.
AB  - The suitability of affinity capillary electrophoresis (ACE) and frontal analysis
      continuous capillary electrophoresis (FACCE) for binding constant determination
      was investigated for complexes between heparin fragments and antithrombin III,
      one of the main target proteins in the coagulation cascade. In a 100 mM ionic
      strength phosphate buffer (pH 7.4), ACE was suitable to determine weak to medium
      interactions developed by short oligomeric heparin fragments, but it failed for
      decasaccharide, which presents a more complex irreversible interaction. However
      FACCE allowed evaluating the binding constant for these longer oligomeric
      fragments. Both experimental approaches were complementary for a wide variety of
      heparinic fragments.

PMID- 16965781
TI  - Chromatographic elution profile of an analyte involved in reversible chemical
      reaction of the type A + B <--> AB.
AB  - The chromatographic peak profile of the analyte involved in a chemical reaction
      of the type A + B <--> AB is considered using method of the apparent adsorption
      isotherm. The apparent isotherms derived are nonlinear even under assumption of
      Henry isotherms of individual solutes. Nonlinearity of apparent adsorption
      isotherm results in peak distortion. The resulted chromatographic peak profile
      depends on several factors such as the equilibrium constant K(mob) and Henry
      constants of the solutes. Simulated peak profiles of solutes involved in the
      chemical reaction are presented as illustration of influence of various factors.

PMID- 16965782
TI  - Comparison of retention models for polymers 1. Poly(ethylene glycol)s.
AB  - The suitability of three different retention models to predict the retention
      times of poly(ethylene glycol)s (PEGs) in gradient and isocratic chromatography
      was investigated. The models investigated were the linear (LSSM) and the
      quadratic solvent strength model (QSSM). In addition, a model describing the
      retention behaviour of polymers was extended to account for gradient elution
      (PM). It was found that all models are suited to properly predict gradient
      retention volumes provided the extraction of the analyte specific parameters is
      performed from gradient experiments as well. The LSSM and QSSM on principle
      cannot describe retention behaviour under critical or SEC conditions. Since the
      PM is designed to cover all three modes of polymer chromatography, it is
      therefore superior to the other models. However, the determination of the analyte
      specific parameters, which are needed to calibrate the retention behaviour,
      strongly depend on the suitable selection of initial experiments. A useful
      strategy for a purposeful selection of these calibration experiments is proposed.

PMID- 16965783
TI  - Enantioseparation of cis and trans nucleosides, aromatic analogues of stavudine,
      by capillary electrophoresis and high-performance liquid chromatography.
AB  - Compounds 1-4 are diastereoisomeric thymine derivatives of isochroman aromatic
      analogues of stavudine, an approved drug. Both capillary electrophoresis (CE) and
      high-performance liquid chromatography (HPLC) techniques were used to separate
      these species with high resolution and thus permit the determination of
      enantiomeric excess. Chiral selectivity was developed using anionic (highly
      sulfated) cyclodextrins as chiral selectors in CE and amylose, cellulose and
      cyclodextrin chiral stationary phases by HPLC. The HPLC method was found to be
      more efficient than the CE method and was applied, after validation
      (repeatability, limit of detection, limit of quantification) to follow and
      quantify the kinetics of a stereoselective esterification.

PMID- 16965784
TI  - Solvents effects on the conformational order of triacontyl modified silica gels
      as evaluated by Fourier transform infrared spectroscopy.
AB  - C30 alkyl modified silica gels have attracted much attention because of their
      enhanced shape selectivity for various types of analytes, which for instance
      cannot be separated with conventional C8 and C18 stationary phases. Since the
      retention processes strongly depend on the nature of solvents and composition of
      the stationary phases, a FTIR study was conducted to evaluate the influence of
      solvents on the conformational order of the alkyl chains in C30 alkyl modified
      silica gels. Variable temperature IR measurements are carried out between 273 and
      353 K in the presence of polar and nonpolar solvents. Information about the
      conformational behavior of the tethered alkyl chains is derived from the analysis
      of the symmetric and antisymmetric CH2 stretching band regions. Polar solvents
      show both enhanced conformational order and disorder of the alkyl chains -
      irrespective of temperature - when compared to dry C30 alkyl modified silica
      gels, while nonpolar solvents in general give rise to enhanced conformational
      disorder in the alkyl chain region. Moreover, for polar solvents a correlation
      exists between the stretching band position, reflecting alkyl chain
      conformational order, and the solvent solvatochromic parameter pi*. Finally, both
      partition and adsorption models are considered to play an important role for the
      solvent-alkyl chain interactions which in turn determines the conformational
      order of the alkyl chains and thus the chromatographic properties of these
      phases.

PMID- 16965785
TI  - Effect of residues remaining in the injection liner of a gas chromatograph on the
      quantification of polycyclic aromatic hydrocarbons by isotope dilution mass
      spectrometry using deuterium-labeled internal standards.
AB  - We have investigated the differences in response ratios of native polycyclic
      aromatic hydrocarbons (native PAHs)/13C-labeled PAHs (13C-PAHs) and of native
      PAHs/deuterium-labeled PAHs (PAHs-d) in a calibration solution containing at
      trace concentrations (< 1 microg mL(-1)) by gas chromatography-mass spectrometry.
      Only the ratios of native PAHs/PAHs-d decreased significantly (p < 0.05)
      accompanied with increase of residue amounts originated from immediately before
      injected solution. Since the analytical results using PAHs-d as internal
      standards were significantly lower than those using 13C-PAHs whatever solutions
      were injected immediately before (p < 0.05, 1.9-13.2%), 13C-PAHs gave more
      accurate results.

PMID- 16965786
TI  - Comparison of high-performance liquid chromatography of cyclotriphosphazene
      derivatives with one or two equivalent stereogenic centres.
AB  - High-performance liquid chromatographic (HPLC) methods have been developed for
      investigating the stereogenic properties of two analogous series of dibenzylamino
      derivatives of cyclotriphosphazene containing either one or two equivalent
      stereogenic centres. Separation of the enantiomers of all the racemic compounds
      has been investigated by chiral HPLC using Whelk-01 and Chiralcel OD columns. In
      all cases, conditions for separation of enantiomers have been found using a Whelk
      01 column with different ratios of tetrahydrofuran in n-hexane as the mobile
      phase. It is found that both the separation factor (alpha) and resolution factor
      (R(S)) of molecules with two equivalent stereogenic centres are greater than
      those for analogues with only one centre.

PMID- 16965787
TI  - Selective and sensitive trace analysis of sulfur mustard with thermal desorption
      and two-dimensional gas chromatography-mass spectrometry.
AB  - An improved method is presented for the trace analysis of sulfur mustard (HD) in
      biological samples, such as blood and tissue from laboratory animals. Using the
      internal standard method and liquid-liquid extraction with ethyl acetate, up to
      400 microL of the extract was injected by thermal desorption from Tenax and
      analyzed by two-dimensional GC-MS/EI in SIM mode. The analysis was compared with
      a direct GC injection. Reversed thermal desorption was used as a tool for
      handling heavily contaminated (fat) samples, thus preventing contamination of the
      injection system and pre-column. A successful analytical configuration has been
      set up for the bioanalysis of HD at the low, toxicologically relevant pM level. A
      detection limit of 10 pg mL(-1) blood or pg g(-1) tissue of sulfur mustard
      (S/N=3) was established by using this configuration.

PMID- 16965788
TI  - New Q membrane scale-down model for process-scale antibody purification.
AB  - Process-scale antibody production requires polishing steps with extremely high
      product throughput and robust operation. In this communication, the Sartobind Q
      membrane adsorber for process-scale antibody production is evaluated as an
      alternative to Q column chromatography. Although the capacity seen with large
      scale membrane adsorbers is competitive with column chromatography, the same
      throughput is not achieved with the current scale-down models. The operational
      issues currently found in membrane scale-down models, including backpressure,
      which significantly compromises the membrane's capacity, were examined. A new
      scale-down model was designed to mimic the liquid flow path found in the large
      scale capsule, and a new process capacity equivalent at both small and large
      scale was successfully achieved. Results of a 4-model virus study with a
      redesigned Sartobind Q absorber scale-down model at the new process capacity are
      presented.

PMID- 16965789
TI  - Identification of smooth and rough forms in cultures of Brucella melitensis
      strains by flow cytometry.
AB  - Brucella melitensis strains may occur as either smooth or rough variants
      depending on the expression of O-polysaccharides (OPS) as a component of the
      bacterial outer membrane lipopolysaccharide (LPS). The wboA gene, which codes for
      the enzyme glycosyl transferase, is essential for the assembly of O-chain in
      Brucella. Deletion of wboA in smooth virulent B. melitensis 16M results in a
      rough mutant designated WRR51. We developed a flow cytometric method to determine
      the proportion of B. melitensis cells displaying surface O-polysaccharide (OPS)
      in liquid culture. OPS was detected using polyclonal antibodies from rabbits
      immunized with smooth (S) or rough (R) Brucella LPS. First, we evaluated the
      binding of these antibodies to 16M (S), WRR51 (R) and complemented WRR51
      expressing the wboA gene (S) as well as to their corresponding GFP-expressing
      derivative strains 16M/GFP, WRR51/GFP and WRR51/GFP+wboA. The rough mutants did
      not react with anti-S-LPS nor did the smooth strains react with anti-R-LPS.
      Second, using different ratios of 16M/GFP and WRR51/GFP, we were able to detect
      the presence of 1% rough bacteria spiked into a sample of smooth organisms.
      Third, we evaluated the purity of cultures of B. melitensis strains grown in a
      fermenter. These flow cytometric methods may be useful for quality control of
      process development for large-scale vaccine production.

PMID- 16965790
TI  - Visual discriminations of spokes, sectors, and circles by the honeybee (Apis
      mellifera).
AB  - A new cue for visual discrimination by the honeybee has been demonstrated. Bees
      detected the position of the centre of symmetry of radial patterns of spokes,
      sectors, and circles relative to their point of choice in the learning process,
      irrespective of the pattern. When trained with one of these patterns versus a
      blank target, the bees discriminated a shift in the position of the centre of
      symmetry by as little as 5 degrees , in some cases with unfamiliar test patterns.
      A pattern of spokes or rings also stabilized the vision of the bees in the
      horizontal plane so that the position of a plain black area could then be
      discriminated. In other experiments, bees discriminated half of a pattern of
      radial spokes or concentric circles from the other half, cut either vertically or
      horizontally, and irrespective of scale. Therefore these patterns were not
      detected by preformed combinations of orientation detectors or global templates
      with a single output. Instead, the crucial cue for detecting edges as radial or
      circular was the coincidence of responses of numerous local edge detectors having
      the appropriate convergence to a hub. Edges that converged towards a hub were
      detected by the bees as radial, and edges at right angles to these were parts of
      circles, irrespective of the actual pattern. Breaking the patterns of spokes or
      circles into rows of squares spoiled the discrimination if the squares were
      separately resolved. Alternatively, breaking the pattern into short bars that
      were separately resolved spoiled the discrimination when the bars subtended less
      than 3 degrees . The local feature detectors for spokes and circles therefore
      resembled those of the orientation detectors in being short, independent, and
      unable to span gaps of more than 3 degrees . In conclusion, radial and circular
      patterns were identified by the regional coincidences and convergence of local
      detectors of edge orientation, and the positions of the centres of symmetry were
      remembered as landmarks that helped locate the reward, but the patterns
      themselves were not remembered.

PMID- 16965791
TI  - Solution structure of the Hdm2 C2H2C4 RING, a domain critical for ubiquitination
      of p53.
AB  - Regulation of the transcriptional response to the tumor suppressor p53 occurs at
      many levels, including control of its transcriptional activity, and of its
      stability and concentration within the cell. p53 stability is regulated by the
      protein Hdm2, an E3 ubiquitin ligase that binds to p53 and promotes its
      ubiquitination and degradation. The C-terminal domain of Hdm2, which is critical
      for this activity, has been classified as a RING domain on the basis of sequence
      homology, although it lacks the canonical set of zinc ligands (RING domains
      typically have C3HC4 or C4C4 zinc coordination). Here, we report the solution
      structure of the C2H2C4 RING domain of Hdm2(429-491), which reveals a symmetrical
      dimer with a unique cross-brace zinc-binding scheme. Each subunit has one Cys4 Zn
      site and one His2Cys2 Zn site. The global fold of each subunit is similar to
      those reported for other RING domains, with a compact betabetaalphabeta fold, a
      small hydrophobic core, and two Zn ions, which are essential for maintaining the
      domain structure. The dimer structure is maintained by an extensive interface
      that buries a large hydrophobic area on each subunit. It has been proposed that
      Hdm2 and its homologue HdmX form a stable heterodimer through their RING domains,
      resulting in a synergistic increase in observed E3 activity. To test this
      proposal, we prepared an HdmX RING construct and showed by NMR titration that it
      forms a tight 1:1 complex with the Hdm2 RING. The resonances most perturbed by
      heterodimer formation are located within the subunit interface of the homodimer,
      far removed from the surface expected to form the docking site of the E2
      ubiquitin-conjugating enzyme, providing a structure-based rationale for the
      function of the RING domains in p53 ubiquitination.

PMID- 16965792
TI  - Identification and characterization of the nuclear localization/retention signal
      in the EWS proto-oncoprotein.
AB  - Ewing sarcoma (EWS) protein, a member of a large family of RNA-binding proteins,
      contains an N-terminal transcriptional activation domain (EAD) and a C-terminal
      RNA-binding domain (RBD). Due to its multifunctional properties EWS protein is
      involved in processes such as gene expression, RNA processing and transport, and
      cell signaling. Chimeric EWS proteins generated by chromosomal translocations
      cause malignant tumors. EWS protein is located predominantly in the nucleus, but
      was found also in the cytosol and associated with the cell membrane. The
      determinants responsible for the nuclear localization of the protein were as yet
      unknown. We identified the nuclear localization signal of EWS protein at its C
      terminus (C-NLS), which is required for the nuclear import and retention of the
      protein. The C-NLS sequence is conserved in related proto-oncoproteins suggesting
      an NLS function also in these proteins. Two arginine residues, due to their
      positive charge, a proline residue and a tyrosine residue are essential for C-NLS
      function. The nuclear localization of EWS protein is independent of the regions
      in RBD containing numerous arginine methylation sites, RNA-recognition and zinc
      finger motifs. Regions in EAD guide the subnuclear partition of EWS protein and
      contain another but different NLS that allows nucleocytoplasmic shuttling of the
      N-terminal domain.

PMID- 16965793
TI  - Macro- and meiofaunal recolonisation of dredged material used for habitat
      enhancement: temporal patterns in community development.
AB  - In recent years, dredged material has become regarded as a potential resource and
      used to create and/or improve intertidal habitats (i.e., beneficial use). This
      paper presents the results of a sampling programme to investigate the long-term
      (42 months post-recharge) macro- and meiofaunal recolonisation processes of a
      beneficial use scheme in south-east England. While univariate indices of
      community structure indicated that the scheme's meiofaunal community was never
      significantly different from that of a nearby reference area, such attributes for
      macrofauna were continually significantly below those of the reference area,
      although this was not the case for all reference stations. Multivariate analyses
      revealed that macro- and meiofaunal community structures were always
      significantly different from those of the reference communities. We discuss the
      factors responsible for these observations and propose that assessing recovery of
      a beneficial use scheme should be undertaken using pre-defined criteria in
      addition to comparisons with a reference site.

PMID- 16965794
TI  - Sub-judice.

PMID- 16965796
TI  - Development and evaluation of tuberculosis screening scores in Brazilian prisons.
AB  - BACKGROUND: Tuberculosis (TB) is highly endemic in Rio de Janeiro State prisons.
      In addition to TB screening at entry and passive case detection, active case
      identification may be warranted. OBJECTIVES: To develop and evaluate performances
      of scores aimed at identifying "tuberculosis suspects" in order to target TB
      screening among inmates. METHODS: Systematic chest X-ray screening was carried
      out in two prisons (n=1910). TB was diagnosed among individuals with X-ray
      abnormalities by sputum microscopic examination and culture or, if
      bacteriological results were negative, by response to TB treatment. Using this
      strategy as a reference, the clinical score proposed in WHO guidelines "TB
      Control in Prisons" was evaluated. Using the same variables in a logistic
      regression comparing TB and non-TB cases, another score was developed and
      evaluated. Finally, a 'new score', based on socio-demographic and clinical
      variables was developed and evaluated. RESULTS: When applied to our study
      population (prevalence of active TB: 4.6%), these scores missed many TB cases
      (sensitivities: 56%, 72%, 74%, respectively). Among the "TB suspects", the
      probability of finding TB cases was low (positive predictive value: 10%). The
      scores had high negative predictive values (>97%); specificities (75%, 60%, 67%)
      were low. Performances were similarly poor for smear-negative and smear-positive
      cases. CONCLUSION: The scores investigated performed poorly and would be
      unhelpful to target TB screening. Therefore, systematic X-ray screening may be
      considered, at least during the initial stages of the reinforced TB programme, in
      order to reduce the impressive burden of TB.

PMID- 16965797
TI  - Getting strategic about the environment and health.
AB  - Historically, the physical environment has been a target for public health policy
      across the globe. This remains the case in developing countries where the
      enduring infectious and toxic challenge posed by the environment is tangible and
      its health impact is manifest. However, in Western societies, the relevance of
      the environment to health has become obscured. Even when this is not the case,
      the perspective is usually narrow, centering on specific toxic, infectious or
      allergenic agents in particular environmental compartments. It is rare for
      importance to be given to a health-determining role for the environment acting
      through broader psychosocial mechanisms. The result is that environmental
      manipulation is seen as a cornerstone of the public health response for
      comparatively few health concerns. This paper considers how public health
      policies and action on the physical environment may be pursued more optimally.
      The need for a more strategic approach, which employs a new conceptual model that
      recognizes the complexity and contextual issues affecting the relationship
      between the environment and health but retains sufficient flexibility and
      simplicity to have practical application, is identified. Building on recent work,
      a model is proposed and pointers are given for its use in a practical context.

PMID- 16965798
TI  - Modulation of estrogen receptor transactivation and estrogen-induced gene
      expression by ormeloxifene-a triphenylethylene derivative.
AB  - The study was aimed to investigate the interaction of D,L-ormeloxifene (Orm), a
      triphenylethylene and its hydroxy derivative with estrogen receptor subtypes
      alpha and beta, its influence on ERE-driven transcriptional activation and
      progesterone receptor expression. In competitive binding experiments using human
      recombinant ERalpha and ERbeta, Orm showed interaction with both ER subtypes,
      with more selectivity and higher affinity towards ERalpha (8.8%) as compared to
      ERbeta (3%). In case of 7-hydroxy derivative, the relative binding affinity for
      both ERs was enhanced several folds. Orm showed lower Ki, i.e. higher affinity
      for ERalpha (250 nM) than for ERbeta (750 nM). It was observed that Orm promoted
      the formation of ER-ERE complexes in uterine tissue extract whereas its hydroxy
      derivative showed inhibitory effects. Transient co-transfection assay in COS-1
      cells using ERE-luciferase reporter construct, revealed that Orm showed
      estrogenic response whereas its hydroxy-derivative was potent antiestrogen at
      ERalpha at transcription level. In immature rats, Orm (2 mg/kg) was associated
      with less increase in uterine weight and in luminal epithelial cell height than
      E2 or Tam. Orm also induced the expression of PR mRNA but the expression level
      was significantly less than estradiol treated group. These results suggest that
      ER-ERE complexes formed under the influence of 7-hydroxy Orm appear to be
      transcriptionally less effective hence antagonizing the E2-regulated gene
      expression in this target tissue.

PMID- 16965799
TI  - Molecular barcoding, DNA from snake venom, and toxinological research:
      Considerations and concerns.
AB  - The problem of species identification in toxinological research and solutions
      such as molecular barcoding and DNA extraction from venom samples are addressed.
      Molecular barcoding is controversial with both perceived advantages and inherent
      problems. A method of species identification utilizing mitochondrial DNA from
      venom has been identified. This method could result in deemphasizing the
      importance of obtaining detailed information on the venom source prior to
      analysis. Additional concerns include; a cost prohibitive factor, intraspecific
      venom variation, and venom processing issues. As researchers demand more
      stringent records and verification, venom suppliers may be prompted to implement
      improved methods and controls.

PMID- 16965800
TI  - Determination of polybrominated diphenyl ethers (PBDEs) in fish samples from
      rivers and estuaries in Taiwan.
AB  - Polybrominated diphenyl ethers (PBDEs) have been used extensively over the past
      two decades as flame retardants in many types of polymers, and have been found to
      be a class of contaminants of concern. Measurements of PBDEs in various
      environmental matrices from Sweden, Holland, Japan, North America, and elsewhere
      have been reported. We report data of PBDEs in fish samples taken from six rivers
      and three estuaries in Taiwan. Seven PBDE congeners were observed in all sixty
      samples. BDE-47 was found to be the dominant congener in all waters, and BDE-154
      contributed more than BDE-99 and BDE-100. Nonetheless, BDE-154 and BDE-183 were
      the predominant congeners in some species studied. These results are somewhat
      different from those from other countries, where the pattern is typically BDE-47
      > 99 >100 >154, 153, and is postulated to be due to the extensive use of octa-BDE
      rather than penta-BDE in Taiwan. The average concentration distribution across
      all samples of the sum of PBDE congeners ranged from 30.6 ng/g lipid to 281 ng/g
      lipid. The concentrations of PBDEs in fishes reported here are higher than those
      reported from European countries, but lower than those from the United States.

PMID- 16965801
TI  - Effect of clays, metal oxides, and organic matter on rhamnolipid biosurfactant
      sorption by soil.
AB  - Rhamnolipids produced by Pseudomonas aeruginosa have been proposed as soil
      washing agents for enhanced removal of metal and organic contaminants from soil.
      A potential limitation for the application of rhamnolipids is sorption by soil
      matrix components. The objective of this study is to empirically determine the
      contribution of representative soil constituents (clays, metal oxides, and
      organic matter) to sorption of the rhamnolipid form most efficient at metal
      complexation (monorhamnolipid). Sorption studies show that monorhamnolipid (R1)
      sorption is concentration dependent. At low R1 concentrations that are relevant
      for enhancing organic contaminant biodegradation, R1 sorption followed the order:
      hematite (Fe(2)O(3))>kaolinite>MnO(2) approximately illite approximately Ca
      montmorillonite>gibbsite (Al(OH)(3))>humic acid-coated silica. At high R1
      concentrations, relevant for use in complexation/removal of metals or organics,
      R1 sorption followed the order: illite>>humic acid-coated silica>Ca
      montmorillonite>hematite>MnO(2)>gibbsite approximately kaolinite. These results
      allowed prediction of R1 sorption by a series of six soils. Finally, a comparison
      of R1 and R2 (dirhamnolipid) shows that the R1 form sorbs more strongly alone
      than when in a mixture of both the R1 and R2 forms. The information presented can
      be used to estimate, on an individual soil basis, the extent of rhamnolipid
      sorption. This is important for determining: (1) whether rhamnolipid addition is
      a feasible remediation option and (2) the amount of rhamnolipid required to
      efficiently remove the contaminant.

PMID- 16965802
TI  - Did the lateral enamel of Neandertal anterior teeth grow differently from that of
      modern humans?
AB  - The formation of lateral enamel in Neandertal anterior teeth has been the subject
      of recent studies. When compared to the anterior teeth of modern humans from
      diverse regions (Point Hope, Alaska; Newcastle upon Tyne, England; southern
      Africa), Neandertal anterior teeth appear to fall within the modern human range
      of variation for lateral enamel formation time. However, the lateral enamel
      growth curves of Neandertals are more linear than those of these modern human
      samples. Other researchers have found that the lateral enamel growth curves of
      Neandertals are more linear than those of Upper Paleolithic and Mesolithic modern
      humans as well. The statistical significance of this apparent difference between
      Neandertal and modern human lateral enamel growth curves is analyzed here. The
      more linear Neandertal enamel growth curves result from the smaller percentage of
      total perikymata located in the cervical halves of their teeth. The percentage of
      total perikymata in the cervical halves of teeth is therefore compared between
      the Neandertal sample (n=56 teeth) and each modern human population sample: Inuit
      (n=65 teeth), southern African (n=114 teeth), and northern European (n=115
      teeth). There are 18 such comparisons (6 tooth types, Neandertals vs. each of the
      three modern human populations). Eighteen additional comparisons are made among
      the modern human population samples. Statistically significant differences are
      found for 16 of the 18 Neandertal vs. modern human comparisons but for only two
      of the 18 modern human comparisons. Statistical analyses repeated for subsamples
      of less worn teeth show a similar pattern. Because surface curvature is thought
      to affect perikymata spacing, we also conducted measurements to assess surface
      curvature in thirty teeth. Our analysis shows that surface curvature is not a
      factor in this lateral enamel growth difference between Neandertals and modern
      humans.

PMID- 16965803
TI  - Population systematics of chimpanzees using molar morphometrics.
AB  - When dental morphological variation within extant species is used as a guideline
      to partition variation within fossil samples into species, the underlying
      assumption is that fossil species are equivalent to extant species. This is the
      case despite the fact that dental morphology, which is commonly used to
      differentiate fossil species, is rarely used to differentiate extant species.
      Aspects of external morphology, ecology, behavior, breeding patterns, and
      molecular structure that are used to delineate living species are generally not
      available for fossils. In this paper, the utility of dental evidence for sorting
      fossil samples into species is evaluated by testing whether molar occlusal
      morphology is capable of sorting populations of Pan into the species and
      subspecies already well-established by nondental evidence. The dentitions of 341
      chimpanzee individuals, sampled from regions throughout equatorial Africa, were
      sorted into 16 populations using rivers to demarcate the boundaries between
      populations. Digital-imaging software was used to measure 15 traits on the
      occlusal surface of each upper molar and 19 on each lower molar. After applying
      size adjustments, size-transformed and untransformed variables were subjected to
      discriminant analysis, with separate analyses carried out for each molar type.
      Results indicate that populations of Pan troglodytes and Pan paniscus are well
      differentiated at all molar positions. Populations of P. t. verus are distinct
      from other populations of P. troglodytes. Populations of P. t. troglodytes and P.
      t. schweinfurthii show close dental similarity. A distinct population is
      recognized at the Nigeria-Cameroon border, indicating the presence of P. t.
      vellerosus. The concordance between the patterns of diversity recognized by this
      study and other molecular and nonmolecular studies indicates that paleontological
      species that are similar to species of Pan in terms of size and patterns of
      diversification may be differentiated using molar morphology.

PMID- 16965804
TI  - Allelic variation in the CNDP1 gene and its lack of association with longevity
      and coronary heart disease.
AB  - Carnosine, a cytoprotective dipeptide found at very high concentrations in
      skeletal muscle, heart and brain, is cleaved in blood by serum carnosinase which
      is encoded by the CNDP1 gene. We recently found that homozygosity of a 5-leucine
      variant in the leader peptide of this enzyme protects diabetes mellitus patients
      against nephropathy. Hypothesising that the same allele could also be associated
      with longevity or a reduced incidence of cardiovascular problems, we examined the
      frequency of CNDP1 alleles in German centenarians, patients with premature
      coronary heart disease, and matched controls. A total of 1382 individuals was
      investigated. The 5-leucine allele was the most common allele in all groups
      investigated. There was no difference in allele or genotype frequency between
      centenarians and their control group, or between cardiovascular patients and
      their control group. The recently identified functional carnosinase variant
      therefore does neither contribute to longevity nor protect against coronary heart
      disease in our probands. In addition to the known trinucleotide repeat alleles in
      the CNDP1 gene, we detected a rare 8-leucine allele, a rare duplication,
      p.L13_V15dup, and a more common frameshift deletion, L17fsX20. Homozygosity for
      L17fsX20, estimated to have a prevalence of approximately 1:20,000, would be
      expected to cause carnosinaemia, an autosomal recessive trait with uncertain
      clinical relevance.

PMID- 16965805
TI  - Midkine and its receptor in regenerating rat skeletal muscle after bupivacaine
      injection.
AB  - Midkine (MK) is a multifunctional cytokine and heparin-binding growth factor with
      neurotrophic activity. MK and its receptor were examined for up to 14 days in a
      chemically injured rat muscle regeneration process caused by the injection of
      bupivacaine using immunohistochemical and Western blot analysis. Although MK
      immunoreactivity was not detectable in the mature uninjured skeletal muscle, MK
      was strongly detected in the regenerating muscle cells. MK immunoreactivity was
      observed in the myoblast-like cells and myotubes, which were desmin-positive
      cells, whereas it was not detectable in the surviving normal muscle fibers. Most
      myotubes labeling for desmin showed MK immunoreactivity 5-7days after the injury.
      However, MK immunoreactivity was not detected 14 days after the injury.
      Immunoreactivity of low-density lipoprotein receptor-related protein (LRP), a
      cell membrane receptor of MK, was detected in the regenerating muscle cells,
      whereas it was not detected in the normal adult skeletal muscle and surviving
      muscle. These findings suggested that MK was involved. MK may have a role for
      differentiation during skeletal muscle regeneration and may be taken up in an
      autocrine fashion with LRP.

PMID- 16965806
TI  - Medical and non-medical protection standards for ultrasound and infrasound.
AB  - Protection from inappropriate or hazardous exposure to ultrasound is controlled
      through international standards and national regulations. IEC standard 60601 part
      1 establishes requirements for the mechanical, electrical, chemical and thermal
      safety for all electro-medical equipment. The associated part 2 standard for
      diagnostic medical ultrasonic equipment sets no upper limits on ultrasonic
      exposure. Instead, safety indices are defined that are intended to advise users
      on the degree of thermal and mechanical hazard. At present the display of these
      safety indices satisfies regulatory requirements in both the USA and Europe.
      Nevertheless there are reservations about the effectiveness of this approach to
      protection management. In the USA, there are national regulatory limits on
      diagnostic exposure, based on acoustic output from clinical equipment in use over
      20 years ago. The IEC 60601 part 2 standard for therapeutic equipment sets 3 W
      cm(-2) as the limit on acoustic intensity. Transducer surface temperature is
      controlled for both diagnostic and therapy devices. For airborne ultrasound,
      interim guidelines on limits of human exposure published by the IRPA are now 2
      decades old. A limit on sound pressure level of 100 dB for the general population
      is recommended. The absence of protection standards for infrasound relates to
      difficulties in measurement at these low frequencies.

PMID- 16965808
TI  - Effects of liquid storage on amidase activity, DNA fragmentation and motility of
      turkey spermatozoa.
AB  - Short-term liquid storage of turkey semen is of great interest in the management
      of turkey reproduction due to the extensive use of artificial insemination. This
      study examined changes in DNA fragmentation (using a comet assay), sperm motility
      characteristics (using computer-aided sperm analysis), and amidase activity
      (using a colorimetric assay) of turkey sperm stored for 24 and 48 h. In addition
      we found that turkey spermatozoa contain besides acrosin, additional two serine
      proteinases of molecular weight of 34 and 42 kDa. We found that, after 48 h of
      liquid storage, decreases in sperm motility characteristics and increases in
      amidase activity and DNA fragmentation occurred. An increase of amidase activity
      was found after 24h. Decreases in sperm motility and increase in DNA
      fragmentation were found after 48 h of storage. These data suggest that a
      decrease in turkey sperm quality during short-term storage is related to
      disturbances to the acrosome, presumably related to premature activation of
      acrosomal serine proteinases, and to a lesser extent a decrease in sperm motility
      characteristics and damage of sperm DNA.

PMID- 16965809
TI  - A novel sex-specific DNA marker in Columbidae birds.
AB  - That most Columbidae birds have no conspicuous sexual dimorphism often makes it
      difficult to identify their sex on the basis of external morphology. In the
      present study, we report a novel sex-specific DNA marker in Columbidae birds. DNA
      was extracted from one member of this bird group, Streptopelia orientalis (S.
      orientalis, oriental turtle dove), and used to identify a female-specific DNA
      marker using a random amplified polymorphic DNA (RAPD) fingerprinting. One
      hundred and sixty random primers were used for the RAPD-PCR reactions. When using
      the OPAV17 primer, a novel 902 bp sex-specific PCR product was amplified from
      known female birds. This fragment of DNA was cloned and sequenced. Two primers,
      TurSexOPAV17-F and TurSexOPAV17-R, were designed from the cloned sex-specific
      sequence, and were successfully used to amplify a 777 bp female-specific fragment
      using PCR from S. orientalis DNA. This sex-specific marker was also amplified
      from genomic DNA samples of two other female Columbidae, S. chinensis and Columba
      livia. Sequence analysis showed that this novel sex-specific marker was highly
      conserved amongst these three bird species. In contrast, the PCR product was not
      amplified from male DNA of these species, nor from either sex of the S. chinensis
      formosa birds. Therefore, we concluded that our novel marker can be used to
      rapidly and accurately identify the sex of birds from three species of
      Columbidae.

PMID- 16965811
TI  - Human bone marrow stromal cells: In vitro expansion and differentiation for bone
      engineering.
AB  - Stromal cells from marrow hold a great promise for bone regeneration. Even if
      they are already being exploited in many clinical settings, the biological basis
      for the source and maintenance of their proliferation/differentiation potential
      after in vitro isolation and expansion needs further investigation. Most studies
      on osteogenic differentiation of marrow stromal cells (MSC) have been performed
      using bone marrow from the iliac crest. In this study, MSC were derived from
      spare femoral bone marrow obtained during hip replacement surgery from 20 adult
      donors. After in vitro isolation the cells were grown in osteogenic medium, and
      their proliferation and differentiation analysed during in vitro expansion. We
      found that MSC isolated from the femur of adult patients consistently maintain an
      osteogenic potential. Using biochemical signals, these cells turn to fully
      differentiated osteoblasts with a predictable set of molecular and phenotypic
      events of in vitro bone deposition. When seeded on polycaprolactone-based
      scaffold or surfaces, the proliferation and mineralization of femur-derived MSC
      were modulated by the surface chemistry/topography. Despite remarkable
      differences between individual colony-forming ability, alkaline phosphatase
      production, and mineralization ability, these cells are a potential source for
      bone engineering, either by direct autologous reimplantation or by ex vivo
      expansion and reimplantation combined to a proper scaffold.

PMID- 16965812
TI  - Amphiphilic polyanhydrides for protein stabilization and release.
AB  - The overall goal of this research is to design novel amphiphilic biodegradable
      systems based on polyanhydrides for the stabilization and sustained release of
      peptides and proteins. Accordingly, copolymers of the anhydrides, 1,6-bis(p
      carboxyphenoxy)hexane (CPH) and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane
      (CPTEG), which are monomer-containing oligomeric ethylene glycol moieties, have
      been synthesized. Microspheres of different CPTEG:CPH compositions have been
      fabricated by two non-aqueous methods: solid/oil/oil double emulsion and
      cryogenic atomization. The ability of this amphiphilic polymeric system to
      stabilize model proteins (i.e., lysozyme and ovalbumin) was investigated. The
      structure of both the encapsulated as well as the released protein was monitored
      using gel electrophoresis, circular dichroism, and fluorescence spectroscopy. It
      was found that the CPTEG:CPH system preserves the structural hierarchy of the
      encapsulated proteins. Activity studies of the released protein indicate the
      CPTEG:CPH system retains the biological activity of the released protein. These
      results are promising for future in vivo studies, which involve the design of
      novel biodegradable polyanhydride carriers for the stabilization and sustained
      release of therapeutic peptides and proteins.

PMID- 16965813
TI  - Association of PAT proteins with lipid storage droplets in term fetal membranes.
AB  - As depots for neutral lipids, lipid storage droplets (LDs) accumulate with
      advancing gestation within the fetal membranes. Little is currently known about
      the proteins associated with the LDs of these cells. The PAT family [perilipin,
      adipose differentiation-related protein (ADRP), and tail-interacting protein of
      47 kilodaltons (TIP47)] represents a unique group of proteins thought to
      contribute to LD formation and function. We examined the association of each of
      the PAT proteins with LDs of term fetal membranes. We found that large LDs of
      amnion epithelial cells were reactive for neutral lipid stains and simultaneously
      encoated with ADRP and TIP47, but not perilipin. Within the remaining cell types,
      LDs were frequently co-labeled with antibodies recognizing ADRP and TIP47;
      however, in cells harboring only small LDs, the majority of TIP47 labeling was
      cytoplasmic. Structures labeled with perilipin antibodies were present only in
      chorion laeve trophoblasts. Gene and protein expression analyses suggested this
      to be a small molecular weight perilipin isoform, such as that seen in
      steroidogenic cells. We conclude that LDs are heterogeneous among differing cell
      types of the fetal membranes. Subclassification of LDs based on associated
      proteins suggests that these organelles may serve specialized functions within
      individual cells.

PMID- 16965814
TI  - "A finer and fairer future": commodifying wage earners in American pulp science
      fiction.
AB  - Long-neglected by scholars, the pulp science fiction (SF) magazines of the
      Gernsback era (1926-1937) are due for re-examination. Presumed to be sub-literary
      stories for boys or, paradoxically, escapist leisure reading for practicing
      scientists and technicians, the SF from this period is actually neither. It is a
      powerful resource for understanding the ways ordinary people engaged with the
      promise and peril of industrial modernity. Published by a passionate entrepreneur
      seeking fame and fortune, composed by writers paid piecework rates and read by
      young science and technology enthusiasts aspiring to authentic remunerative work,
      the earliest pulp SF necessarily provoked inter-class discussions about labor,
      management, production and consumption.

PMID- 16965815
TI  - Different neutralization efficiency of neutralizing monoclonal antibodies against
      avian influenza H5N1 virus to virus strains from different hosts.
AB  - BALB/c mice were immunized with formalin-treated influenza A/CK/Hubei/327/2004
      virus. Six monoclonal antibodies specific to HA were selected, designed 1H8,
      1D11, 2B7, 2C9, 2H4 and 4C9, respectively. The six Mabs probed linear epitopes by
      western blot assays. In ELISA additivity assays, the low additivity indexes (< or
      =28.3) of each pair Mabs indicated that the epitopes recognized by the six Mabs
      were located on the globular head of HA1. The neutralization activity of anti-HA1
      Mabs and chicken polyclonal sera to various AIV H5N1 strains from different hosts
      was followed by virus neutralization with MDCK cells. All Mabs except 2C9 and
      chicken polyclonal serum showed highest neutralizing activity to lowly virulent
      A/Duck/XF/XFY/2004 from different phylogenetic lineage, and lowest neutralization
      efficiency to highly virulent A/CK/XF/XFJ/2004. For the other two highly virulent
      viruses, 1D11, 2H4, 4C9 and chicken polyclonal sera had higher neutralization to
      A/Goose/ZF/ZFE/2004 than A/CK/Hubei/327/2004, and 1H8 and 2B7 had considerable
      level of neutralizing efficiency to them. These findings suggested that the
      neutralizing antibodies showed lower neutralization efficiency to highly virulent
      virus strains than lowly virulent virus strains and strong cross-neutralizing
      reaction between virus strains located in different phylogenetic lineages.
      Moreover, the neutralizing Mabs could more efficiently neutralize AIV H5N1
      strains from the natural hosts generally, such as waterfowl.

PMID- 16965816
TI  - Parental exposure to enriched uranium induced delayed hyperactivity in rat
      offspring.
AB  - Several recent reports suggest that chronic exposure to uranium could induce
      behavioural effects in adult rats. As the immature brains are known to be more
      susceptible to toxic effects, rats were observed in an open field, in a Y-maze
      and in an elevated plus-maze at 2, 5 and 9 months old after exposure to enriched
      uranium (40 mg l-1) during gestation and lactation. The rats exposed to enriched
      uranium showed a significant decrease in alternation in the Y-maze at 2 months
      old which reflects a slight decrease in the spatial working memory capacities as
      previously described in adult rats. However, the main result was a delayed
      hyperactivity in the rats exposed to enriched uranium, which appeared to a slight
      extent at 5 months old and was more evident at 9 months old. Although this effect
      could not be directly explained by some uranium accumulation in the target
      organs, this experiment showed that early exposure to enriched uranium can induce
      a very late effect on the rat behaviour and that such studies should not be
      restricted to the effects observed on young rats.

PMID- 16965817
TI  - Synthesis, structure and biological activity of cobalt(II) and copper(II)
      complexes of valine-derived schiff bases.
AB  - We have synthesized two cobalt(II) 2 and copper(II) 3 complexes of valine-derived
      Schiff bases. The obtained complexes were characterized by elemental analysis, FT
      IR and X-ray diffraction. Biological studies of complexes 2 and 3 had been
      carried out in vitro for antimicrobial activity against Gram-positive, Gram
      negative bacteria and human pathogenic fungi. Compound 3 was proven to be a broad
      spectrum agent, showed a significant inhibition of the growth of Gram-positive
      bacteria (Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus
      subtilis, Micrococcus luteus), and pathogenic fungi (Candida spp., Cryptococcus
      neoformans, Rhodothece glutinis, Saccharomyces cerevisia, Aspergillus spp.,
      Rhizopus nigricans) tested and a moderate activity against Gram-negative bacteria
      (Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris and Enterobacter
      aerogenes) tested. The in vitro cytotoxicity of compound 3 was evaluated using
      hemolytic assay, in which the compound 3 was found to be non-toxic to human
      erythrocytes even at a concentration of 500mug/mL.

PMID- 16965818
TI  - A gold(I) complex with a vitamin K3 derivative: characterization and antitumoral
      activity.
AB  - Reaction of the vitamin K(3) derivative menadione sodium bisulfite
      thiosemicarbazone (NaK(3)TSC) with chloro(triethylphosphine)gold(I) afforded the
      complex [AuPEt(3)(K(3)TSC)]. This compound consists of discrete molecules in
      which the metal is almost linearly coordinated to P and S. Preliminary in vitro
      screening showed significant anti-cancer activity, notably against the cisplatin
      resistant cell line A2780cis.

PMID- 16965819
TI  - Potential influence of Asp in the Ca2+ coordination position 5 of parvalbumin on
      the calcium-binding affinity: a computational study.
AB  - Parvalbumins (PV) are calcium-binding proteins, all sharing the common helix-loop
      helix (EF-hand) motif. This motif contains a central twelve-residue Ca(2+)
      binding loop with the flanking helices positioned roughly perpendicular to each
      other. The precise role of these coordination residues has been the subject of
      intense studies. In this work, we focus on the coordination position 5 in the CD
      Ca(2+)-binding site of silver hake parvalbumin isoform B (SHPV-B). The most
      common residue at site 5 of calcium-binding loop in canonical EF-hands is Asp
      [B.J. Marsden, G.S. Shaw, B.D. Sykes, Biochem. Cell Biol. 68 (1990) 587-601], but
      in the CD site of PV, this position is almost always serine (Ser). The
      substitution of Ser with Asp will add the 5th carboxylate residue in the CD
      coordination sphere. However, as predicted by the acid pair hypothesis, the
      Ca(2+)-binding affinity would be maximized in an EF-hand motif that has four
      carboxylate ligands paired along the +/-x, and +/-z-axes [R.E. Reid, R.S. Hodges,
      J. Theor. Biol. 84 (1980) 401-444]. Molecular dynamics simulations and free
      energy calculations were employed to investigate the influence of Ser to Asp
      mutation at position 5 on calcium-binding affinity. We found that the Asp variant
      exhibited remarkable stability during the entire molecular dynamics simulation,
      with not only the retention of the Ca(2+)-binding site, but also increased
      compactness in the coordination sphere. The S55D fragment also accommodated
      Ca(2+) well. We conclude that the reason why Asp which is the most common residue
      at site 5 of calcium-binding loop in canonical EF-hands has never been identified
      at this position experimentally for PVs might be related to its physiological
      functions.

PMID- 16965820
TI  - New approach to the activation of anti-cancer pro-drugs by metalloporphyrin-based
      cytochrome P450 mimics in all-aqueous biologically relevant system.
AB  - The low-molecular weight water-soluble Fe(III) and Mn(III) porphyrins--in
      biologically relevant phosphate-buffered saline medium with ascorbic acid as a
      source of electrons, under aerobic conditions but without co-oxidant - catalyze
      the hydroxylation of anti-cancer drug cyclophosphamide to active metabolite 4
      hydroxycyclophosphamide in yields similar or higher than those typically obtained
      by the action of liver enzymes in vivo. The Fe(III) meso tetrakis(2,6-difluoro-3
      sulfonatophenyl)porphyrin, highly electron-deficient at the metal site, was the
      most effective catalyst. If proven viable in vivo, this methodology could be
      expanded to localized or systemic activation of the entire family of
      oxazaphosphorine-based (and many other) anti-cancer drugs and become a powerful
      tool for an aggressive treatment of tumors with less toxic side effects to the
      patient.

PMID- 16965821
TI  - Melioidosis and rainfall in Kuala Lumpur, Malaysia.

PMID- 16965822
TI  - HPLC separation of some purine and pyrimidine derivatives on Chromolith
      Performance Si monolithic column.
AB  - The chromatographic behavior of some purines and pyrimidines on a monolithic
      Chromolith Performance Si column under normal-phase high-performance liquid
      chromatography mode has been studied. Column pressure, column efficiency and
      selectivity of Chromolith Performance Si column were compared to those of
      conventional spherical 5 microm silica packed columns Econosphere Silica and
      Zorbax Rx-SIL. The investigation has shown that application of Chromolith
      Performance Si column for analysis of polar solutes can reduce the separation
      time without sacrificing column efficiency and selectivity. Improvement of the
      monolithic silica column efficiency for polar solutes is observed when ternary
      mobile phases (mixtures of hexane-isopropanol with ethylene glycol, water or
      acetonitrile) are applied.

PMID- 16965823
TI  - Automatic detection of slow wave sleep using two channel electro-oculography.
AB  - An automatic method was developed for detecting slow wave sleep (SWS). The
      automatic method is based on a two-channel electro-oculography (EOG) with left
      mastoid (M1) as reference. Synchronous electroencephalographic (EEG) activity was
      detected by calculating cross-correlation between the two EOG channels by using
      0.5-6 Hz band. An amplitude criterion was used for detecting slow waves and beta
      power 18-30 Hz was used to exclude artefacts. The automatic scoring was compared
      to a standard visual sleep scoring based on EOG, central EEG and submental EMG.
      Sleep EEG and EOG were recorded from 265 subjects. The optimal cross-correlation,
      amplitude and beta thresholds were derived using data from 133 training subjects
      and then applied to the data from different 132 validation subjects. Results were
      most sensitive to the changes in the amplitude criteria. Cohen's Kappa between
      the visual and the new developed automatic scoring in separating non-SWS and SWS
      was substantial (0.70) with epoch-by-epoch agreement of 93%. SWS epoch detection
      sensitivity was 75% and specificity was 96%. Also the total amount of slow waves,
      slow wave time (SWT), was estimated. The advantage of the automatic method is
      that it could be applied during online recordings using only four disposable self
      adhesive electrodes.

PMID- 16965824
TI  - Subjective well-being and 'male depression' in male adolescents.
AB  - BACKGROUND: The concept of male depression is based on the hypothesis that
      typical symptoms of depression in men often seem to be masked by non-typical male
      distress symptoms not considered in common depression inventories. Although there
      is a large amount of clinical evidence, scientific evidence is still lacking. The
      study aims at further validating the concept of male depression, by obtaining
      information on symptoms reported by males, and analyzing the dimensional
      structure of the Gotland Scale of Male Depression [Rutz, W., 1999. Improvement of
      care for people suffering from depression: The need for comprehensive education.
      International Clinical Psychopharmacology 14, 27-33.]. METHODS: A community
      sample of male adolescents aged 18 (n=1004) was asked to complete the WHO-5 Well
      being Index [Bech, P., 1998. Quality of life in the psychiatric patient. London:
      Mosby-Wolfe.] and the Gotland Scale of Male Depression [Rutz, W., 1999.
      Improvement of care for people suffering from depression: The need for
      comprehensive education. International Clinical Psychopharmacology 14, 27-33.].
      Principal component analysis with promax rotation was calculated to analyze the
      dimensional structure of the Gotland Scale. Cluster center analyses were used to
      classify the sample according to the symptoms' characteristics. RESULTS: General
      well-being was rather reduced, and 22% of the respondents were seen to be at risk
      of male depression. There was no evidence for the hypothesis that young males
      tend to mask their depressive symptoms with distress symptoms. Depressive and
      male distress symptoms appeared to be mixed in a dominant factor, while male
      distress symptoms constitute an additional minor factor. A cluster of 38% of
      those at risk for depression could be identified who reported significantly
      elevated male distress symptoms. Irritability turned out to be the single item of
      the Gotland Scale with the highest item-total correlation. LIMITATIONS: Risk of
      depression was not assessed by an additional depression scale or evaluated by a
      clinical rating. CONCLUSIONS: Male distress symptoms should be considered when
      diagnosing depression in men. Further research is needed with respect to
      comorbidity and differential diagnoses, which should also include bipolar
      depression.

PMID- 16965825
TI  - Interleukin-1 alpha but not interleukin-1 beta gene polymorphism is associated
      with polycystic ovary syndrome.
AB  - Interleukin-1 (IL1) is a multifunctional cytokine and IL1-mediated inflammatory
      processes have been proposed to influence the processes of ovulation,
      fertilization and implantation. All these parameters are also affected in women
      with polycystic ovary syndrome (PCOS). This study investigated the association of
      common polymorphisms of the interleukin-1 genes (IL1A and IL1B) with the
      occurrence and clinical characteristics of PCOS. We evaluated one polymorphism of
      the IL1alpha gene (IL1A C[-889]T) and two of the IL1beta gene (IL1B promoter C[
      511]T and IL1B exon 5 position +3953) in 105 Caucasian women with PCOS and 102
      healthy Caucasian controls by polymerase chain reaction. For the mutated IL1A
      allele, allele frequencies in women with PCOS and controls were 60% and 46%,
      respectively, versus 40% and 54%, respectively, for the wild type allele. Allele
      frequencies in women with PCOS and controls were 59% (54%) and 61% (41%),
      respectively, for the mutated IL1B promoter (mutated IL1B exon 5) and 41% (46%)
      and 39% (59%), respectively, for the wild type alleles. Presence of a
      polymorphism in the interleukin-1alpha but not the interleukin-1beta gene was
      found to correlate with the occurrence of PCOS (p=0.04; odds ratio 1.8). The
      serum level of FSH and subsequent LH/FSH ratio correlated with the polymorphism
      of IL1A within the PCOS group (p=0.005 and 0.01, respectively). We have shown
      that a common polymorphism of the interleukin-1alpha but not interleukin-1beta
      gene is associated with the presence of PCOS and with clinical parameters of
      women affected by this condition.

PMID- 16965826
TI  - Relationship of delay aversion and response inhibition to extinction learning,
      aggression, and sexual behaviour.
AB  - Impulsivity is an important symptom of many psychiatric disorders, and can be
      divided into two subtypes: response inhibition deficits and delay aversion. In
      the present study, we investigated the relationship between delay aversion and
      response inhibition, both to each other and to locomotion, extinction of
      conditioned responses, sexual behaviour, and aggressive behaviour. To that end,
      we quantified the behaviour of 24 rats in several tests. To measure response
      inhibition, rats were trained in a stop-signal task. In this operant task, rats
      were rewarded food if they inhibited execution of a response after presentation
      of an audible stop-signal. Delay aversion was measured in an operant task in
      which rats made a choice between a small, immediately available reward and a
      large reward available after a delay. The results showed that delay aversion and
      response inhibition were independent. Responses during extinction and various
      measures of aggressive behaviour were positively correlated to delay aversion.
      The speed of go-trials in the stop-task was correlated to non-aggressive
      behaviour. We conclude that the role of response inhibition in various behaviours
      is small, but delay aversion in particular contributes to several other
      behaviours, such as aggressive behaviour and extinction.

PMID- 16965827
TI  - Treatment results of 165 pediatric patients with non-metastatic nasopharyngeal
      carcinoma: a Rare Cancer Network study.
AB  - PURPOSE: This Rare Cancer Network (RCN) study was performed in pediatric
      nasopharyngeal carcinoma (PNPC) patients to evaluate the optimal dose of
      radiotherapy and to determine prognostic factors. PATIENTS AND METHODS: The study
      included 165 patients with the diagnosis of PNPC treated between 1978 and 2003.
      The median age was 14 years. There were 3 (1.8%) patients with stage I, 1 (0.6%)
      with IIA, 10 (6.1%) with IIB, 60 (36.4%) with III, 44 (26.7%) with IVA, and 47
      (29%) with IVB disease. While 21 (12.7%) patients were treated with radiotherapy
      (RT) alone, 144 (87.3%) received chemotherapy and RT. The median follow-up time
      was 48 months. RESULTS: The actuarial 5-year overall survival (OS) was 77.4% (95%
      CI: 70.06-84.72), whereas the actuarial 5-year disease-free survival (DFS) rate
      was 68.8% (95% CI: 61.33-76.31). In multivariate analysis, unfavorable factors
      were age >14 years for LRC (p=0.04); male gender for DMFS (p=0.03); T3/T4 disease
      for LRFS (p=0.01); and N3 disease for DFS (p=0.002) and OS (p=0.002); EBRT dose
      of less than 66 Gy for LRFS (p=0.02) and LRRFS (p=0.0028); and patients treated
      with RT alone for LRFS (p=0.0001), LRRFS (p=0.007) and DFS (p=0.02). CONCLUSION:
      Our results support the current practice of using combined radiation and
      chemotherapy for optimal treatment of NPC. However, research should be encouraged
      in an attempt to reduce the potential for long-term sequelae in pediatric
      patients given their relatively favorable prognosis and potential for longevity.

PMID- 16965828
TI  - Primate disrupted-in-schizophrenia-1 (DISC1): high divergence of a gene for major
      mental illnesses in recent evolutionary history.
AB  - Here we analyze the species conservation of disrupted-in-schizophrenia-1 (DISC1)
      gene, a susceptibility gene for schizophrenia. We cloned cDNA of DISC1 and
      characterized DISC1 protein in monkey brains and compared their features with
      those in a variety of species, including humans, rodents and lower vertebrates.
      Sequences of human and monkey DISC1 are very similar for both nucleotides and
      amino acids, in sharp contrast to those of rodents; this is reminiscent of G72,
      another gene involved in major mental illnesses. Bioinformatic cross-species
      comparisons identified a portion of DISC1 sequences in chicken and Caenorhabditis
      elegans, but failed to find DISC1 in Drosophila. In contrast to sequence
      differences, the regional expression profile of DISC1 is well conserved between
      rodents and primates in that levels of DISC1 mRNA and protein are higher in the
      hippocampus and the cerebral cortex, and much lower in cerebellum in adult
      brains. The findings of this study may suggest overall patterns of evolution of
      genes for psychiatric disorders, and thus assist in production of genetically
      engineered mice, and the interpretation of the underlying mechanisms of
      psychiatric conditions.

PMID- 16965829
TI  - Over-expression of severe acute respiratory syndrome coronavirus 3b protein
      induces both apoptosis and necrosis in Vero E6 cells.
AB  - The genome of the severe acute respiratory syndrome coronavirus encodes for eight
      accessory viral proteins with no known homologues in other coronaviruses. One of
      these is the 3b protein, which is encoded by the second open reading frame in
      subgenomic RNA 3 and contains 154 amino acids. Here, a detailed time-course study
      was performed to compare the apoptosis and necrosis profiles induced by full
      length 3b, a 3b mutant that was deleted by 30 amino acids from the C terminus
      (3bDelta124-154) and the classical apoptosis inducer, Bax. Our results showed
      that Vero E6 cells transfected with a construct for expressing 3b underwent
      necrosis as early as 6h after transfection and underwent simultaneous necrosis
      and apoptosis at later time-points. At all the time-points analysed, the
      apoptosis induced by the expression of 3b was less than the level induced by Bax
      but the level of necrosis was comparable. The 3bDelta124-154 mutant behaves in a
      similar manner indicating that the localization of the 3b protein does not seems
      to be important for the cell-death pathways since full-length 3b is localized
      predominantly to the nucleolus, while the mutant is found to be concentrated in
      the peri-nuclear regions. To our knowledge, this is the first report of the
      induction of necrosis by a SARS-CoV protein.

PMID- 16965830
TI  - Demonstration of receptor binding properties of VP2 of very virulent strain
      infectious bursal disease virus on Vero cells.
AB  - Tissue culture adaptation of infectious bursal disease virus (IBDV) results in
      alternation of three residues on its major capsid protein VP2 and these residues
      may engage in receptor binding. Although the key of successful infection of
      tissue culture adapted IBDV in tissue cultures was defined as the virus entering
      steps, mechanism of the adaptation is poorly understood. In this study,
      recombinant VP2s of an attenuated strain (D78) and a very virulent strain (HK46)
      of IBDV tagged with rabbit immunoglobulin G heavy chain were expressed in
      mammalian cells, generating RAVP2 and RVVP2, respectively, in high purity. Using
      flow cytometry, both RAVP2 and RVVP2 were demonstrated to bind with Vero cells
      while these bindings were blocked by D78 viral particles, implying both very
      virulent IBDVs (vvIBDVs) and attenuated IBDVs bind to Vero cells through the same
      receptor(s). Since vvIBDVs cannot be propagated directly in tissue cultures, the
      specific binding between RVVP2 and Vero cells suggests the barrier for tissue
      culture adaptation may be beyond the virus attachment process.

PMID- 16965831
TI  - Synthesis of minus-strand copies of a viral transgene during viral infections of
      transgenic plants.
AB  - Viral transgenes designed to provide resistance to specific plant viruses
      frequently consist of the coat protein gene and a contiguous 3' untranslated
      region (3'UTR) of viral origin. In many RNA viruses the viral 3'UTR establishes a
      recognition and initiation site for viral RNA replication. Thus the transgenic
      transcript may contain a functional virus replication site. Experiments were
      designed to determine if a challenging virus would recognize this replication
      site on a nuclear derived transcript and synthesize the complementary RNA. These
      data demonstrate that upon infection by a virus that recognizes the viral
      replication site, a full-length complement of the transgenic transcript is
      produced. In these experiments the replication complex of Brome Mosaic bromovirus
      recognized the transgenic transcript derived from a Cowpea Chlorotic Mottle
      bromovirus transgene. The resulting RNA may contribute to RNA recombination
      events.

PMID- 16965832
TI  - Asymptomatic circulation of HEV71 in Norway.
AB  - Widespread circulation of human enterovirus 71 was discovered in a prospective
      study of fecal samples obtained from healthy Norwegian children. Molecular
      characterization of the virus determined that it belonged to genotype C1.
      Complete sequencing of this strain, HEV71 804/NO/03, revealed differences in the
      5'UTR and polymerase with respect to more pathogenic genotypes that may explain
      its reduced neurovirulence.

PMID- 16965833
TI  - Capacity planning for cardiac catheterization: a case study.
AB  - BACKGROUND: Excessive waiting for procedures such as cardiac catheterization is
      an important issue for health care systems. Delays are generally attributed to a
      mismatch between demand and available capacity. Furthermore, due to the dynamic
      nature of short-term referral rates, procedure times, and patients' medical
      urgency, all of which are important contributors to the problem of excessive
      waiting time, it has been difficult to predict capacity needs accurately. The
      objective of our paper is to demonstrate how such calculations could be
      performed. METHODS: After constructing a patient flow model and populating it
      with appropriate data from 16 consecutive months of operations (n=6215 referrals)
      of a regional cardiac centre in Ontario, we used computer simulation to simulate
      the operations of catheterization laboratories in several "what-if" scenarios. We
      divided the patients into three urgency categories: U1--hospitalized patients, U2
      -urgent outpatients, U3--elective outpatients. We tested the accuracy of the
      model by comparing a 1-year sample of computer simulation with actual data which
      resulted in a highly significant correlation of 0.94. RESULTS: We observed from
      the referral cohort that waiting times were long, both overall and within each
      urgency category. We observed from the simulation models that: (1) a one-time
      infusion of capacity to clear the backlog failed to reduce the waiting times; (2)
      targeting extra capacity to highest urgency categories reduced waiting times
      overall and also benefited low urgency patients for whom specific increased
      capacity was not earmarked; (3) there were no significant effects on waiting
      times if in some cases patients or referring physicians were able to choose their
      cath physician; and (4) in situations where the arrival rates increased overall
      or within specific urgency categories, waiting times increased dramatically and
      failed to return to baseline for several months to years for the low urgency
      patients. Efficiency of the labs within the existing capacity could be improved
      by: (1) reducing changeover time between cases (2) externalizing and
      standardizing many of the pre- and post-procedural management of the patients,
      and (3) more carefully balancing the booking to reduce both slack and overtime.
      INTERPRETATION: Capacity determination is a complex and dynamic process. A
      combination of available clinical and administrative data, along with a computer
      simulation model, helps predict capacity needs and is the most appropriate
      strategy to minimize waiting of patients for procedures. This approach is
      generalizable and can lead to more effective management of waiting lists for a
      variety of procedures.

PMID- 16965834
TI  - The anti-apoptotic livin gene is an important determinant for the apoptotic
      resistance of non-small cell lung cancer cells.
AB  - Cancer cells are typically characterized by increased resistance towards
      apoptosis. Livin (alternatively called ML-IAP or KIAP) is an anti-apoptotic
      protein which is expressed in several cancer forms. Using real-time reverse
      transcription-polymerase chain reaction (RT-PCR), we confirmed livin expression
      in a significant portion of non-small cell lung cancer (NSCLC) tissue samples
      and, in addition, detected livin expression in a number of NSCLC cell lines. In
      order to elucidate whether livin contributes to the apoptotic resistance of lung
      cancer cells, we silenced endogenous livin expression in a panel of cancer
      derived NSCLC cell lines by RNA interference (RNAi). We observed that the
      targeted inhibition of livin strongly sensitized NSCLC cells to different pro
      apoptotic stimuli, such as UV-irradiation or the chemotherapeutic drug etoposide.
      In addition, long-term silencing of livin blocked the outgrowth of NSCLC cells in
      colony formation assays. These effects of small interfering (si)RNA were specific
      for livin-expressing tumor cells. Our results indicate that Livin is an important
      contributor to the apoptosis resistance of NSCLC cells and may serve as a novel
      molecular target for therapeutic inhibition in NSCLC.

PMID- 16965835
TI  - Intravenous angiotensin and salt appetite in rats.
AB  - Circulating angiotensin II is crucial for the activation of salt appetite after
      sodium depletion. We tested if angiotensin (ANG) II infused intravenously at 50
      ng/kg/min overnight (chronic) can mimic the rapid salt appetite similar to
      furosemide and overnight sodium depletion. In experiment 1, rats received chronic
      ANG II or vehicle infusions all night with access to water and chow but no saline
      solution. In the morning, the infusions continued, but half of the vehicle
      infused group was switched to ANG II (acute). Thirty minutes after the switch,
      all rats received 10 mg/kg furosemide SC. One hour later they were provided water
      and 0.3 M NaCl to drink. Rats infused with vehicle or acute ANG drank little, but
      the chronic ANG group drank 11+/-1 ml of saline in 90 min. In experiment 2, the
      furosemide was omitted, and a group receiving a chronic infusion of phenylephrine
      at 6.25 microg/kg/min was included. The chronic ANG group drank 10+/-1 ml saline
      in 90 min, but the phenylephrine group, which also incurred a significant
      negative sodium balance overnight, drank little. Thus, an overnight infusion of
      ANG II is sufficient to mimic the robust expression of salt appetite as observed
      after furosemide and overnight sodium depletion.

PMID- 16965836
TI  - Consumer-perceived quality in 'traditional' food chains: the case of the Greek
      meat supply chain.
AB  - Recent food scares have increased consumer concern about meat safety. However,
      the Greek 'traditional' meat supply chain from producers to local butchers does
      not seem to realise the pressing consumer demand for certified meat quality. Or
      is it that, in such food chains, this demand is not so pressing yet? The present
      paper seeks to answer this question based on a survey conducted in the Athens
      area, involving a sample of 268 participants responsible for food purchasing
      decisions. The survey mainly aims to develop an integrated model of factors that
      affect consumer-perceived meat quality and to develop the profile of different
      consumer segments in relation to these perceptions. The substantial findings of
      the survey include the fact that, despite their enormous per capita consumption,
      the majority of consumers are not particularly involved in the meat-purchasing
      process. Rather they attach importance to visual intrinsic quality cues evaluated
      in a pre-purchasing context. In this respect, intrinsic quality cues are assigned
      a role similar to that of quality certification; coupled with the choice of
      traditional channels and the resulting personal relation with the butcher, they
      can be understood as efforts to decrease risk of the purchasing decision.
      Moreover, consumers with such behaviour seem to relate domestic country of origin
      of meat mostly with perceptions of general safety. Finally, a small, but
      promising trend with substantial marketing implications of frequent purchases of
      chicken and pork at supermarkets should not be ignored.

PMID- 16965837
TI  - Vasoactive intestinal peptide enhances wound healing and proliferation of human
      bronchial epithelial cells.
AB  - In the present study, we investigated the effects of vasoactive intestinal
      peptide (VIP) on wound healing of bronchial epithelium. Wound healing of the
      mechanical damaged human bronchial epithelial cells (HBEC) was observed in the
      absence or presence of VIP. Effects of VIP on chemotactic migration, cell
      proliferation of HBEC were also tested. HBEC chemotaxis was assessed by the blind
      well chamber technique, the cell cycle was determined by flow cytometry, and cell
      proliferation was determined by measuring the expression of proliferating cell
      nuclear antigen Ki67. Effects of VIP on epithelial E-cadherins protein and mRNA
      were also measured by immunohistochemistry and RT-PCR. The results showed that
      VIP accelerated the recovery of wound area of HBEC. VIP increased the migration
      and proliferation of HBEC, and these effects were blocked by a VPAC1 receptor
      antagonist. VIP also increased the expression of E-cadherin mRNA and protein in
      HBEC, suggesting that protective effects of VIP on wound healing may be related
      to its ability to increase the expression of E-cadherin. In conclusion, VIP has
      protective effects against human bronchial epithelial cell damage, and the
      beneficial effects of VIP might be mediated, at least in part, by VPAC1, and
      associated with increased expression of E-cadherin.

PMID- 16965838
TI  - The effect of bovine serum albumin on the membrane potential and reactive oxygen
      species generation in succinate-supported isolated brain mitochondria.
AB  - Characteristics of the succinate-supported H(2)O(2) formation were compared in
      mitochondria prepared from guinea-pig brain either by Percoll gradient
      centrifugation or using digitonin. The high rate of H(2)O(2) generation measured
      in mitochondria prepared with digitonin (600.6+/-26.8pmol/min/mg protein) was
      inhibited by rotenone, consistently with a reverse flow of electrons via complex
      I. The rate of H(2)O(2) formation was significantly smaller in Percoll-purified
      mitochondria (252.6+/-17.3pmol/min/mg protein) and this was stimulated by
      rotenone. Since bovine serum albumin (BSA) is usually present in the isolation
      medium used in the digitonin method, systematic study was performed addressing
      the effect of BSA on H(2)O(2) formation. Mitochondria prepared by the digitonin
      method (BSA present in the isolation medium) were highly polarized (185+/-3.2mV)
      and addition of BSA (0.025%) to the assay medium increased H(2)O(2) generation by
      only 50%. In Percoll-purified mitochondria DeltaPsim was more depolarized (171+/
      2mV) and BSA caused hyperpolarization by 10.7+/-1.9mV. H(2)O(2) formation, which
      was largely independent of DeltaPsim, was stimulated by 400%, became highly
      dependent on DeltaPsim and could be inhibited by rotenone in the presence of BSA.
      This shows that in Percoll-purified mitochondria ROS formation via reverse
      electron flow is preferred only when BSA is present in the assay medium. It is
      demonstrated that (i) the presence or absence of BSA could determine the
      mechanism by which ROS is generated in succinate-supported mitochondria and (ii)
      depolarization by about 10mV eliminates reverse electron flow and the remaining
      ROS formation, which is smaller but still significant, is no longer dependent on
      DeltaPsim.

PMID- 16965839
TI  - Dopaminergic neuronal loss in transgenic mice expressing the Parkinson's disease
      associated UCH-L1 I93M mutant.
AB  - The I93M mutation in ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) was
      reported in one German family with autosomal dominant Parkinson's disease (PD).
      The causative role of the mutation has, however, been questioned. We generated
      transgenic (Tg) mice carrying human UCHL1 under control of the PDGF-B promoter;
      two independent lines were generated with the I93M mutation (a high- and low
      expressing line) and one line with wild-type human UCH-L1. We found a significant
      reduction in the dopaminergic neurons in the substantia nigra and the dopamine
      content in the striatum in the high-expressing I93M Tg mice as compared with non
      Tg mice at 20 weeks of age. Although these changes were absent in the low
      expressing I93M Tg mice, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      treatment profoundly reduced dopaminergic neurons in this line as compared with
      wild-type Tg or non-Tg mice. Abnormal neuropathologies were also observed, such
      as silver staining-positive argyrophilic grains in the perikarya of degenerating
      dopaminergic neurons, in I93M Tg mice. The midbrains of I93M Tg mice contained
      increased amounts of insoluble UCH-L1 as compared with those of non-Tg mice,
      perhaps resulting in a toxic gain of function. Collectively, our data represent
      in vivo evidence that expression of UCHL1(I93M) leads to the degeneration of
      dopaminergic neurons.

PMID- 16965840
TI  - Dissociation between hippocampal neuronal loss, astroglial and microglial
      reactivity after pharmacologically induced reverse glutamate transport.
AB  - The inflammatory central nervous system response that involves activated
      microglia and reactive astrocytes may both heal and harm neurons, as inflammatory
      mediators lead to neuroprotection or excitation at one dose but to injury at a
      different concentration. To investigate these complex cellular interactions, L
      trans-pyrrolidine-2,4-dicarboxylate (PDC), a selective substrate inhibitor of
      glutamate transport, was infused during 14 days in the rat hippocampus at three
      different rates: 5, 10 and 25 nmol/h. A microglial reaction appeared at the 5
      nmol/h PDC rate in absence of astroglial reaction and neuronal loss. Microgliosis
      and neuronal death were observed at PDC 10 nmol/h in absence of astrogliosis and
      calcium precipitation, whereas all four aspects were present at the highest rate.
      This dissociation between neuronal loss and astroglial reactivity took place in
      presence of a permanent microglial reaction. These data suggest a specific
      response of microglia to PDC whose neuronal effects may differ with the infused
      dose.

PMID- 16965841
TI  - Longitudinal genetic analysis of executive function in elderly men.
AB  - The objective of this study was to characterize the relative contribution of
      genetic and environmental influences to individual differences in longitudinal
      performance and decline of executive function (EF) using a population-based
      prospective study of male, WWII veteran twins (NHLBI twin study). Three tests of
      EF were administered when the twins were 59-70 years old, with 9- and 13-year
      follow-up. APOE epsilon4 allele status was incorporated in the genetic models to
      determine its contribution to longitudinal genetic variability. Mean EF
      performance significantly worsened over time. EF performance was highly
      genetically correlated across repeat assessment. There were significant genetic
      influences on 9- and 13-year decline in digit symbol performance. For all tasks
      decline over the last 4-year follow-up was influenced by individual-specific
      environmental effects. Controlling for APOE epsilon4 allele presence did not
      appreciably change the magnitude of genetic effects. These results suggest that
      common genetic factors underlie longitudinal EF task performance. Genetic
      influences on EF decline, however, appear to be evident at longer time intervals
      between assessments.

PMID- 16965842
TI  - The derivation of radionuclide transfer parameters for and dose-rates to an adult
      ringed seal (Phoca hispida) in an Arctic environment.
AB  - Radionuclide transfer parameters and dose-rates for an adult ringed seal from
      Svalbard have been determined based on empirical and estimated tissue activity
      concentrations and detailed dietary and habitat information. Whole-body
      equivalent concentration factors determined for anthropogenic radionuclides
      ranged from 10(1) ((90)Sr) to 10(2) ((137)Cs, (238)Pu and (239,240)Pu), while
      natural radionuclides ranged from 10(2) ((210)Pb) to 10(4) ((210)Po). Employing a
      dietary composition of 40% fish, 40% zooplankton and 20% benthic invertebrates, a
      whole-body biological half-life of 29 days was derived for (137)Cs. A total dose
      rate of approximately 0.19microGyh(-1) (1.7mGya(-1)) was derived for an adult
      ringed seal; this dose-rate is virtually entirely attributable to the internal
      components of (210)Po and (40)K. The dose-rates associated with the presence of
      anthropogenically derived radionuclides in the present assessment fall many
      orders of magnitude below the dose-rates at which any biological effects would be
      expected.

PMID- 16965843
TI  - Keith DJ, Ong TK, Martin IC. The role of thoracic computed tomography in staging
      newly-diagnosed oral squamous cell carcinoma. Br J Oral Maxillofac Surg
      2006;44:198-202.

PMID- 16965844
TI  - Priority organic micropollutants in water sources in Flanders and the Netherlands
      and assessment of removal possibilities with nanofiltration.
AB  - The occurrence of organic micropollutants in ground- and surface waters has
      become an important concern for the drinking water industry, mainly because of
      possible related health effects. Due to the polar nature of some of these
      pollutants, they are not completely removed by traditional water treatment
      barriers. This paper offers an overview of priority organic micropollutants and
      their occurrence in Flemish and Dutch water sources. Furthermore, rejection by
      nanofiltration is qualitatively predicted for the selected priority
      micropollutants. The qualitative prediction is based on the values of key solute
      and membrane parameters in nanofiltration. Predicted values are then compared
      with experimental values obtained from literature. Overall, the qualitative
      predictions are roughly in agreement with literature values. Prediction based on
      key parameters may thus prove to be a very quick and useful technique to assess
      the implementation of nanofiltration as a treatment step for organic
      micropollutants in drinking water plant design.

PMID- 16965845
TI  - A benchmark dose analysis for sodium monofluoroacetate (1080) using dichotomous
      toxicity data.
AB  - The use of a benchmark dose (BMD) as an alternative to a no-observed-adverse
      effect-level (NOAEL) approach was investigated as a means to improve current risk
      assessment values of sodium monofluoroacetate (1080). The feasibility of
      implementing the two approaches was investigated for three critical toxicological
      end points, namely cardiomyopathy, testicular toxicity and teratogenic effects
      identified from the few available critical studies. The BMD provides better
      representation of the dose-response relationship, offering an advantage over the
      current NOAEL approach. The calculated BMDs and lower-bound confidence limits
      (BMDLs) for the three end points were estimated using the Weibull, probit and
      quantal linear models for each end point. All models passed the chi2 test
      statistics (p > or = 0.1) for all three toxicity endpoints tested. A benchmark
      response (BMR) of 10% (extra risk) was chosen and the Akaike's information
      criterion (AIC) was used in selecting the appropriate model. The BMDL estimates
      derived were found to be generally slightly higher but comparable to the NOAEL
      for those same endpoints. The BMD(10) and BMDL(10) for cardiomyopathy and
      testicular effects were 0.21 mgkg(-1) bw and 0.10 mgkg(-1) bw, respectively.
      These values are proposed for use in the eventual determination of the tolerable
      daily intake (TDI) for 1080.

PMID- 16965846
TI  - Child access to health services during the economic crisis: An Indonesian
      experience of the safety net program.
AB  - Child health has been a serious problem in Indonesia for several decades. The
      prolonged Indonesian economic crisis in 1997 had a tremendous impact on poor
      children who suffered due to malnutrition. In 1998, the Indonesian government
      launched a broad social safety net program to protect the poor from becoming
      poorer. In the health sector this took the form of Jaring Pengaman Sosial Bidang
      Kesehatan (JPS-BK) or the Social Safety Net in Health Sector program. Adopting
      the model of health services utilization of Andersen and Newman, I examine the
      extent to which JPS-BK contributed to better health services for poor children in
      four provinces, by using a simplified version of Andersen and Newman's model of
      health services utilization which emphasizes the importance of contextual
      determinants. Variables used in the study included child outpatient visits,
      health card possession, household income, and poverty status. Using data sets
      from the JPS-BK longitudinal study, I compared utilization of health services
      between baseline data collection at Rounds One and Three, which was taken a year
      afterward. In addition, I used the Village Potentials data set from the
      Indonesian Bureau of Statistics and employed factor analysis to raise one
      variable representing the village/neighborhood developmental level. Basic
      statistics were used to examine possible changes between study rounds and
      logistic regression was used to examine the effect of health card possession on
      child health services utilization. Two significant improvements occurred during
      the first year of the program: (i) more sick children visited outpatient
      facilities and (ii) more children lived in households possessing health cards.
      The JPS-BK increased the "potential access" that was demonstrated by the
      significant increase in health card possession regardless of the visit, and
      "realized access" that was demonstrated by the significant increase in child
      outpatient visits regardless of health card possession. Further research needs to
      be undertaken to explore the dynamics of outpatient visits and the actual use of
      health cards.

PMID- 16965847
TI  - Oncogenicity evaluation of resveratrol in p53(+/-) (p53 knockout) mice.
AB  - A six-month study was conducted in p53(+/-) mice to evaluate the possible
      oncogenicity of resveratrol (3,5,4'-trihydroxy-trans-stilbene), a cancer
      chemopreventive agent present in grapes and other foods. p53(+/-) mice
      (25/sex/group) received daily gavage exposure to vehicle only (negative control),
      resveratrol doses of 1000, 2000, or 4000 mg/kg/day, or p-cresidine (400
      mg/kg/day; positive control). No mortality was seen in mice receiving the low
      dose of resveratrol. However, the mid and high doses induced mortality associated
      with impaction of the test article in the gastrointestinal tract. Resveratrol had
      no effect on body weight, food consumption, or clinical signs in surviving mice
      in any dose group, but induced dose-related increases in liver weight and serum
      cholesterol in both sexes. Mild anemia was seen in male mice at the high dose
      only; hematologic effects were not seen in females. Histopathology identified the
      kidney (hydronephrosis) and urinary bladder (epithelial hyperplasia) as target
      tissues for resveratrol toxicity. The incidences of both benign and malignant
      tumors in mice exposed to resveratrol were comparable to those in vehicle
      controls. By contrast, the positive control article, p-cresidine, induced urinary
      bladder cancer in both sexes. When administered to p53(+/-) mice at its maximum
      tolerated dose, resveratrol demonstrates no evidence of oncogenicity.

PMID- 16965848
TI  - Effect of the co-administration of phenobarbital, quercetin and mancozeb on
      nitrosomethylurea-induced pancreatic tumors in rats.
AB  - We have previously shown that a single i.p. injection of nitrosomethylurea (NMU)
      in 3-day-old rats orally treated with the pesticide mancozeb (MZ), the flavonoid
      quercetin (Q) or in combination (MZ-Q) induces hyperplasia, atypical acinar cell
      proliferation and carcinoma in situ (CIS) in the pancreas. This work studies the
      effect of oral administration of phenobarbital (PB) on this model of pancreatic
      carcinogenesis. The animals were fed on a diet supplemented by MZ or/and Q from
      the 10th day of pregnancy, thorough lactation and as pups after weaning until
      being sacrificed at week 24. Saline injection with non-supplemented diet was used
      for the control group (SAL). The experimental groups were (1) SAL (control), (2)
      SAL-PB, (3) NMU, (4) NMU-PB, (5) MZ-NMU, (6) MZ-NMU-PB, (7) Q-NMU, (8) Q-NMU-PB,
      (9) MZ-Q-NMU and (10) MZ-Q-NMU-PB. Acinar cell hyperplasia was found in all
      groups of NMU-treated rats. Dysplastic foci (DYS) were seen in groups 3-10 at the
      following percentages: 19, 48, 71, 27, 71, 35, 100 and 30, respectively. CIS were
      recorded in groups 4 to 10 at percentages: 4, 36, 13, 11, 0, 16, 5, respectively.
      CONCLUSION: Although PB, Q or MZ given alone enhance DYS lesions in NMU-treated
      rats, the MZ/Q/PB combined treatments may increase (mainly in males) or decrease
      (mainly in female) the DYS and CIS proportion. Because PB, MZ and Q influence
      P450 enzymes, we suggest that these enzymes play a role in the carcinogenesis
      process.

PMID- 16965849
TI  - Halothane induces oxidative stress and NF-kappaB activation in rat liver:
      protective effect of propofol.
AB  - We investigated the effects of propofol on markers of oxidative stress, nuclear
      factor kappa B (NF-kappaB) activation and inducible nitric oxide synthase (iNOS)
      expression in liver of rats treated with halothane under hypoxic conditions. Male
      Wistar rats received halothane 1%/oxygen 14%, oxygen 14%/propofol 60 mg kg(-1)
      i.p., or halothane 1%/oxygen 14%/propofol 60 mg kg(-1) i.p. Morphological
      examination showed complete loss of architecture with massive necrosis of
      parenchyma in the halothane group, while only minor histological abnormalities
      were observed in rats receiving halothane plus propofol. The cytosolic
      concentration of TBARS and the hydroperoxide-initiated chemiluminescence
      increased significantly in the liver of animals from the halothane group (+62%
      and +40% versus controls, respectively), and this increase was abolished by
      propofol administration. Halothane induced a marked activation of NF-kappaB
      (+180%), and resulted in a significant decrease of the nonphosphorylated form of
      the inhibitor IkappaBalpha (-53%), while phosphorylated IkappaBalpha protein
      level was markedly increased (+146%). Propofol administration lowered these
      effects to +30% (NF-kappaB), -26% (nonphosphorylated IkappaBalpha), and +56%
      (phosphorylated IkappaBalpha). The increase of iNOS protein level (+59%) induced
      by halothane was significantly reduced to +22% by additional administration of
      propofol. Results obtained show that administration of propofol inhibits
      oxidative stress, NF-kappaB nuclear traslocation and iNOS overexpression in liver
      of rats receiving halothane. Propofol treatment, by inhibiting the NF-kappaB
      signal transduction pathway, might block the production of noxious mediators
      involved in the development of halothane-induced injury.

PMID- 16965850
TI  - Sildenafil reduces postoperative adhesion formation in a rat uterine horn model.
AB  - OBJECTIVE: The purpose of this experimental study was to evaluate the effect of
      oral sildenafil on postoperative adhesion formation in rats. STUDY DESIGN: Thirty
      two Wistar Albino rats were subjected to standardized lesion by cauterization of
      the uterine horn and abrasion of the adjacent parietal peritoneum. They were
      randomized to receive sildenafil at a daily dose of 15 mg/kg, 7.5mg/kg and 3.75
      mg/kg or placebo. Sildenafil was administered by gavage 1h before the operation
      and daily for 5 days after the procedure. The extent and severity of adhesions
      were assessed on the 14th postoperative day. RESULT(S): The severity but not
      extent of adhesions in rats given 15 mg/kg sildenafil was significantly less when
      compared with the other groups (<0.001). CONCLUSION: Sildenafil diminishes
      peritoneal adhesion formation in rat.

PMID- 16965851
TI  - Management of placenta accreta: morbidity and outcome.
AB  - OBJECTIVE: The aim of the study was to evaluate our results in the management of
      placenta accreta. STUDY DESIGN: In a retrospective study we reviewed cases of
      placenta accreta diagnosed in two university teaching hospitals between 1993 and
      2003. For a subgroup of patients a conservative approach was attempted. In this
      procedure placenta was left in place until spontaneous resorption. RESULTS: Fifty
      cases (0.12%) of placenta accreta were observed in 41, 119 deliveries during the
      study period. Of the 50 cases, 24 patients (48%) were managed by the standard
      approach and 26 patients (52%) underwent conservative treatment. Additional
      surgical or medical treatment was performed in 35 of the 50 patients (70%). There
      was no maternal death. Overall hysterectomy rate was 40%, 10 patients were
      transferred to intensive care unit (20%), 7 had fever (14%), 5 had endometritis
      (10%) and 19 patients had blood transfusion (38%). Conservative treatment did not
      lead to hysterectomy in 21 cases (80.7%) and failed in 5 (19.3%). During the
      follow-up period, 3 women had successful pregnancy. CONCLUSION: Analysis of
      management of placenta accreta shows that for a subgroup of selected patients a
      conservative approach could preserve subsequent fertility without evident
      increase in morbidity.

PMID- 16965852
TI  - Land-use forecasting and hydrologic model integration for improved land-use
      decision support.
AB  - This paper develops a methodology for integrating a land-use forecasting model
      with an event scale, rainfall-runoff model in support of improving land-use
      policy formulation at the watershed scale. The models selected for integration
      are loosely coupled, structured upon a common GIS platform that facilitates data
      exchange. The hydrologic model HEC-HMS is calibrated for a specific storm event
      that occurred within central Washington State. The land-use forecasting model,
      What If? is implemented to forecast future spatial distributions of low-density
      residential land-uses under low and high population growth estimates. Forecasted
      land-use distribution patterns for the years 2015, 2025, and 2050 are then used
      as land-use data input for the calibrated hydrologic model, keeping all other
      parameters constant. Impacts to the stream discharge hydrograph are predicted as
      the study area becomes increasingly developed as forecasted by What If?. The
      initial results of this integration process demonstrate the synergy that can be
      generated through the linkage of the selected models. The ability to quantifiably
      forecast the potential hydrologic implications of proposed land-use policies
      before their implementation offers land-use decision-makers a valuable tool for
      discerning which proposed land-use alternatives will be effective at minimizing
      storm water runoff.

PMID- 16965853
TI  - Small universal spiking neural P systems.
AB  - In search for small universal computing devices of various types, we consider
      here the case of spiking neural P systems (SN P systems), in two variants: as
      devices that compute functions and as devices that generate sets of numbers. We
      start with the first case and we produce a universal spiking neural P system with
      84 neurons. If a slight generalization of the used rules is adopted, namely, we
      allow rules for producing simultaneously several spikes, then a considerable
      reduction, to 49 neurons, is obtained. For SN P systems used as generators of
      sets of numbers, we find a universal system with restricted rules having 76
      neurons and one with extended rules having 50 neurons.

PMID- 16965854
TI  - Biological significance of cancer-associated sialyl-Tn antigen: modulation of
      malignant phenotype in gastric carcinoma cells.
AB  - The activation of an abnormal glycosylation pathway in cancer cells leads to the
      formation of the sialyl-Tn antigen, blocking regular carbohydrate chain
      elongation. Sialyl-Tn antigen is rarely expressed in normal tissues but is
      aberrantly expressed in a variety of carcinomas, where it constitutes a marker of
      poor prognosis. Although the clinical significance of sialyl-Tn is well
      characterized, a functional role for this glycan and its contribution to cancer
      progression remain to be elucidated. This study evaluates the capability of
      sialyl-Tn to modify processes like cell cycle, apoptosis, actin cytoskeleton
      dynamics, adhesion and motility on ECM components, cell-cell aggregation and
      invasion. De-novo expression of sialyl-Tn leads to major morphological and cell
      behavior alterations in gastric carcinoma cells which were reverted by specific
      antibody blockage. Sialyl-Tn antigen is able to modulate a malignant phenotype
      inducing a more aggressive cell behavior, such as decreased cell-cell aggregation
      and increased ECM adhesion, migration and invasion.

PMID- 16965855
TI  - Amygdala GABA-A receptor involvement in mediating sensory-discriminative and
      affective-motivational pain responses in a rat model of peripheral nerve injury.
AB  - The contribution of the amygdala to neuropathic pain processing in animals has
      not been clearly acknowledged. To assess the relative contribution of amygdala
      GABA-A receptors in mediating sensory-discriminative and affective-motivational
      pain components, the GABA-A receptor agonist muscimol and the antagonist
      bicuculline (both 10-25 ng/microl) were administered by acute bilateral injection
      directly into the central amygdala in rats with a chronic constriction injury
      (CCI). Escape/avoidance behaviour reflecting the affective-motivational dimension
      of pain was measured using a light/dark chamber in combination with
      suprathreshold nociceptive stimulation, and was defined as a shift from the 'non
      aversive' dark area of the chamber to the 'aversive' light area. Hindpaw
      mechanical allodynia and mechanical hyperalgesia thresholds reflecting the
      sensory-discriminative dimension of pain were determined prior to and following
      escape/avoidance testing. Muscimol administration into the amygdala attenuated
      escape/avoidance behaviour and reversed hindpaw mechanical hypersensitivity in
      CCI rats; the magnitude of reduction in escape/avoidance behaviour was 2- to 3
      fold greater than mechanical allodynia. Surprisingly, administration of
      bicuculline also attenuated escape/avoidance behaviour but had no effect on
      nociceptive behaviours. The muscimol-induced reversal of hindpaw mechanical
      hypersensitivity was completely blocked by co-administration of bicuculline, in
      contrast to escape/avoidance behaviour. Motility behaviour was unaffected by
      injection of either drug as determined in the open field test. Thus, amygdala
      GABA-A receptors appear to play an important role in sensory and especially
      affective pain processing in neuropathic rats. Furthermore, after nerve injury
      reflex nociceptive behaviours appear to be under tonic control by descending
      inputs, which originate from or are modulated within the amygdala.

PMID- 16965856
TI  - Determination of the role of conventional, novel and atypical PKC isoforms in the
      expression of morphine tolerance in mice.
AB  - This study comprehensively determines the role of all the major PKC isoforms in
      the expression morphine tolerance. Pseudosubstrate and receptors for activated C
      kinase (RACK) peptides inhibit only a single PKC isoform, while previously tested
      chemical PKC inhibitors simultaneously inhibit multiple isoforms making it
      impossible to determine which PKC isoform mediates morphine tolerance. Tolerance
      can result in a diminished effect during continued exposure to the same amount of
      substance. In rodents, morphine pellets provide sustained exposures to morphine
      leading to the development of tolerance by 72 h. We hypothesized that
      administration of the PKC isoform inhibitors i.c.v. would reverse tolerance and
      reinstate antinociception in the tail immersion and hot plate tests from the
      morphine released solely from the pellet. Inhibitors to PKC alpha, gamma and
      epsilon (100-625 pmol) dose-dependently reinstated antinociception in both tests.
      The PKC beta(I), beta(II), delta, theta, epsilon, eta and xi inhibitors were
      inactive (up to 2500 pmol). In other mice, the degree of morphine tolerance was
      determined by calculating ED50 and potency-ratio values following s.c. morphine
      administration. Morphine s.c. was 5.6-fold less potent in morphine-pelleted vs.
      placebo-pelleted mice. Co-administration of s.c. morphine with the inhibitors
      i.c.v. to either PKC alpha (625 pmol), gamma (100 pmol) or epsilon (400 pmol)
      completely reversed the tolerance so that s.c. morphine was equally potent in
      both placebo- and morphine-pelleted mice. The PKC beta(I), beta(II), delta,
      theta, epsilon, eta and xi inhibitors were inactive. Thus, PKC alpha, gamma and
      epsilon appear to contribute to the expression of morphine tolerance in mice.

PMID- 16965857
TI  - Trypanosomiasis by Trypanosoma vivax in cattle in the Brazilian semiarid:
      Description of an outbreak and lesions in the nervous system.
AB  - An outbreak of trypanosomiasis by Trypanosoma vivax is reported in the semiarid
      of Paraiba, Northeastern Brazil from May to August 2002. Sixty-four cows out of
      130 were affected; 11 died and the other recovered after treatment with
      diminazene aceturate. Affected animals had fever, anemia, weight loss,
      hypoglycemia, increased serum levels of aspartate aminotransferase and, in nine
      cows, nervous signs. All cows with nervous signs died; six of them recovered
      after treatment, but the disease relapsed. Six cows aborted and one delivered a
      calf that died immediately after parturition. Thirty-two out of 100 calves were
      affected and five died. Nervous signs were not observed in the calves. Gross
      lesions were thickening of the meninges, enlarged lymph nodes and prominent white
      pulp of the spleen. The main histological lesion was meningoencephalitis and
      malacia in the brain of cows with nervous signs. No antibodies against
      trypanosomes were found in 33 blood samples collected before the outbreak in the
      affected farm and in 29 samples collected at the same time in two other neighbor
      farms. Until January 2003, all 89 animals tested had antibodies against T. vivax,
      suggesting the occurrence of sub clinical infections in cattle without clinical
      signs. Only two out of 85 serum samples collected on April 2004 were positive for
      T. vivax antibodies. Data obtained suggested that the semiarid region is non
      endemic for trypanosomiasis and that disease occurred due to introduction of the
      parasite in a susceptible population after an apparent rise in the Tabanus spp.
      population.

PMID- 16965858
TI  - Epidemiology and seasonal dynamics of gastrointestinal nematode infections of
      sheep in a semi-arid region of eastern Ethiopia.
AB  - A study on the epidemiology and seasonal dynamics of gastrointestinal nematode
      infections of sheep was carried out in a semi-arid region of eastern Ethiopia for
      2.5 years (May 2003 to September 2005). The experimental flock comprised a total
      of 60 Black Head Ogaden sheep, consisting of four equal groups of young male and
      female and old male and female sheep. These grazed on communal pastures together
      with a larger university flock, as well as with animals owned by neighbouring
      small-holder farmers. A new experimental flock was established each year of the
      study. Parasitological data (EPG, faecal culture L3, PCV and FAMACHA estimates)
      and animal performance (weight change) were recorded each month on all
      experimental animals. In addition, four tracer lambs were assigned each month to
      the flock to determine the seasonal patterns of infective larvae acquired from
      pasture. Results showed distinct seasonal patterns associated with the bi-modal
      annual rainfall. High levels of infection occurred during the short and long rain
      seasons with peaks occurring in May and September of each year. Haemonchus
      contortus was the most prevalent parasite, followed by Trichostrongylus spp.,
      with a number of other nematode species being occasionally recorded. H. contortus
      showed and increased propensity to undergo arrested development during the dry
      seasons. Correlations between EPG and PCV, EPG and FAMACHA eye scores, and PCV
      and FAMACHA eye scores were all highly significant (P<0.001). However, there was
      no significant association between the EPG and LW of the study animals during
      each study year. This information will provide a basis for developing
      epidemiologically based control strategies for gastrointestinal nematode
      parasites that are appropriate for flocks owned by small-holder farmers of semi
      arid areas of eastern Ethiopia.

PMID- 16965859
TI  - Altered nocturnal growth hormone (GH) secretion in obsessive compulsive disorder.
AB  - Nocturnal patterns of growth hormone (GH) in obsessive compulsive disorder (OCD),
      which is physiologically released predominantly during the first half of night,
      have not been reported. However, altered GH responses to pharmacological
      challenges suggest a disturbed function of the somatotropic axis in OCD. In this
      study, nine inpatients with a DSM-IV diagnosis of OCD without comorbid major
      depression (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score >15; HAMD-21
      total score 16) and 9 healthy matched controls were included. Blood of patients
      (7 males, 31.8+/-9.3 years, Y-BOCS: 27.3+/-4.3, HAMD-21: 13.3+/-1.9) and controls
      (7 males, 31.6+/-9.1 years) was drawn every 20 min between 2300 and 0700 h during
      sleep using a long catheter for later GH analysis. Mean plasma GH levels peaked
      at 0040 h, however this peak was significantly blunted in patients (maximum 4.3+/
      1.5 ng/ml) compared to controls (maximum 12.3+/-4.0 ng/ml; p<0.05). In patients
      but not controls two other, smaller peaks were observed (0220 and 0620 h). In
      patients but not in controls, GH values exceeding maximum GH values of the peak
      at 0040 h were observed already at 2300 h or during the second half of night. In
      conclusion, our results indicate that the nocturnal GH secretion in patients with
      OCD is altered compared to controls.

PMID- 16965860
TI  - Rodent rhythmicity studies: Use of unfavorable light regimes.

PMID- 16965861
TI  - A wake-up call: are degenerative diseases provoked by some of our normal food
      constituents? A case for nutrigenomics.

PMID- 16965862
TI  - Potential advantage of studying the lymphatic drainage by sentinel node technique
      and SPECT-CT image fusion for pelvic irradiation of prostate cancer.
AB  - PURPOSE: This study aims to investigate the in vivo drainage of lymphatic spread
      by using the sentinel node (SN) technique and single-photon emission computed
      tomography (SPECT)-computed tomography (CT) image fusion, and to analyze the
      impact of such information on conformal pelvic irradiation. METHODS AND
      MATERIALS: Twenty-three prostate cancer patients, candidates for radical
      prostatectomy already included in a trial studying the SN technique, were
      enrolled. CT and SPECT images were obtained after intraprostate injection of 115
      MBq of 99mTc-nanocolloid, allowing identification of SN and other pelvic lymph
      nodes. Target and nontarget structures, including lymph nodes identified by
      SPECT, were drawn on SPECT-CT fusion images. A three-dimensional conformal
      treatment plan was performed for each patient. RESULTS: Single-photon emission
      computed tomography lymph nodal uptake was detected in 20 of 23 cases (87%). The
      SN was inside the pelvic clinical target volume (CTV2) in 16 of 20 cases (80%)
      and received no less than the prescribed dose in 17 of 20 cases (85%). The most
      frequent locations of SN outside the CTV2 were the common iliac and presacral
      lymph nodes. Sixteen of the 32 other lymph nodes (50%) identified by SPECT were
      found outside the CTV2. Overall, the SN and other intrapelvic lymph nodes
      identified by SPECT were not included in the CTV2 in 5 of 20 (25%) patients.
      CONCLUSIONS: The study of lymphatic drainage can contribute to a better knowledge
      of the in vivo potential pattern of lymph node metastasis in prostate cancer and
      can lead to a modification of treatment volume with consequent optimization of
      pelvic irradiation.

PMID- 16965864
TI  - Intensity-modulated radiotherapy significantly reduces xerostomia compared with
      conventional radiotherapy.
AB  - PURPOSE: Xerostomia is a severe complication after radiotherapy for oropharyngeal
      cancer, as the salivary glands are in close proximity with the primary tumor.
      Intensity-modulated radiotherapy (IMRT) offers theoretical advantages for normal
      tissue sparing. A Phase II study was conducted to determine the value of IMRT for
      salivary output preservation compared with conventional radiotherapy (CRT).
      METHODS AND MATERIALS: A total of 56 patients with oropharyngeal cancer were
      prospectively evaluated. Of these, 30 patients were treated with IMRT and 26 with
      CRT. Stimulated parotid salivary flow was measured before, 6 weeks, and 6 months
      after treatment. A complication was defined as a stimulated parotid flow rate
      <25% of the preradiotherapy flow rate. RESULTS: The mean dose to the parotid
      glands was 48.1 Gy (SD 14 Gy) for CRT and 33.7 Gy (SD 10 Gy) for IMRT (p <
      0.005). The mean parotid flow ratio 6 weeks and 6 months after treatment was
      respectively 41% and 64% for IMRT and respectively 11% and 18% for CRT. As a
      result, 6 weeks after treatment, the number of parotid flow complications was
      significantly lower after IMRT (55%) than after CRT (87%) (p = 0.002). The number
      of complications 6 months after treatment was 56% for IMRT and 81% for CRT (p =
      0.04). CONCLUSIONS: IMRT significantly reduces the number of parotid flow
      complications for patients with oropharyngeal cancer.

PMID- 16965863
TI  - How gender, age, and geography influence the utilization of radiation therapy in
      the management of malignant melanoma.
AB  - PURPOSE: Comparing radiation therapy utilization rates (RTUR) to those predicted
      by best evidence is a useful measure of the equity and accessibility of service
      delivery. In this study the RTUR for melanoma was established for British
      Columbia, Canada, and compared with the rate suggested by the evidence.
      Demographic variables, specifically age, gender, and geography that influenced
      the RTUR were examined with a view to identifying methods of improving
      underutilization. METHODS AND MATERIALS: The RTUR in the management of malignant
      melanoma was taken from British Columbia Cancer registry data for 1986 to 1998.
      Variations in utilization based on age, gender, health authority, stage of
      disease, and referral patterns were analyzed. RESULTS: An RTUR of 11% was
      identified. This was consistent over time. Referral rates decreased between 1986
      and 1998. RT is used mostly for later stage disease. Males were more likely to
      receive RT than females, related to later stage of disease in men. Referral rates
      decreased, but RTUR for referred cases increased, in health authorities that did
      not have a cancer center. CONCLUSIONS: Use of RT is influenced by age and by
      stage of disease. Overall RTUR in British Columbia is lower than suggested by
      best evidence. Referral patterns are influenced by geography. RTUR was higher in
      males, consistent with a different pattern of disease in males compared with
      females.

PMID- 16965865
TI  - Dose-volume modeling of the risk of postoperative pulmonary complications among
      esophageal cancer patients treated with concurrent chemoradiotherapy followed by
      surgery.
AB  - PURPOSE: The aim of this study was to investigate the effect of radiation dose
      distribution in the lung on the risk of postoperative pulmonary complications
      among esophageal cancer patients. METHODS AND MATERIALS: We analyzed data from
      110 patients with esophageal cancer treated with concurrent chemoradiotherapy
      followed by surgery at our institution from 1998 to 2003. The endpoint for
      analysis was postsurgical pneumonia or acute respiratory distress syndrome. Dose
      volume histograms (DVHs) and dose-mass histograms (DMHs) for the whole lung were
      used to fit normal-tissue complication probability (NTCP) models, and the quality
      of fits were compared using bootstrap analysis. RESULTS: Normal-tissue
      complication probability modeling identified that the risk of postoperative
      pulmonary complications was most significantly associated with small absolute
      volumes of lung spared from doses > or = 5 Gy (VS5), that is, exposed to doses <
      5 Gy. However, bootstrap analysis found no significant difference between the
      quality of this model and fits based on other dosimetric parameters, including
      mean lung dose, effective dose, and relative volume of lung receiving > or = 5
      Gy, probably because of correlations among these factors. The choice of DVH vs.
      DMH or the use of fractionation correction did not significantly affect the
      results of the NTCP modeling. The parameter values estimated for the Lyman NTCP
      model were as follows (with 95% confidence intervals in parentheses): n = 1.85
      (0.04, infinity), m = 0.55 (0.22, 1.02), and D50 = 17.5 Gy (9.4 Gy, 102 Gy).
      CONCLUSIONS: In this cohort of esophageal cancer patients, several dosimetric
      parameters including mean lung dose, effective dose, and absolute volume of lung
      receiving < 5 Gy provided similar descriptions of the risk of postoperative
      pulmonary complications as a function of the radiation dose distribution in the
      lung.

PMID- 16965866
TI  - Hypofractionated versus conventionally fractionated radiation therapy for
      prostate carcinoma: updated results of a phase III randomized trial.
AB  - PURPOSE: The aim of this study was to compare the toxicity and efficacy of
      radiation therapy (RT) for localized carcinoma of the prostate, using a
      hypofractionated (55 Gy/20 fractions/4 weeks) vs. a conventionally fractionated
      (64 Gy/32 fractions/6.5 weeks) dose schedule. METHODS AND MATERIALS: A total of
      217 patients were randomized to either the hypofractionated (108 patients) or the
      conventional (109 patients) dose schedule, with planning with two-dimensional
      (2D) CT scan planning methodology in the majority of cases. All patients were
      followed for a median of 48 (6-108) months. Gastrointestinal (GI) and
      genitourinary (GU) toxicity was evaluated before RT and after its completion
      using modified late effects of normal tissue-subjective, objective, management,
      analytic (LENT-SOMA) scales and the European Organization for Research and
      Treatment of Cancer sexual function questionnaire. Efficacy of RT based on
      clinical, radiologic, and prostate-specific antigen data were also evaluated at
      baseline and after RT. RESULTS: Gastrointestinal and GU toxicity persisted 5
      years after RT and did not differ between the two dose schedules other than in
      regard to urgency of defecation. However, 1-month GI toxicity was not only worse
      in patients with the hypofractionated RT schedule but also adversely affected
      daily activities. Nadir prostate-specific antigen values occurred at a median of
      18.0 (3.0-54.0) months after RT. A total of 76 biochemical relapses, with or
      without clinical relapses, have occurred since; of these, 37 were in the
      hypofractionated and 39 in the conventional schedule. The 5-year biochemical +/-
      clinical relapse-free and overall survival was 55.9% and 85.3% respectively for
      all patients, and did not differ between the two schedules. CONCLUSIONS:
      Radiation therapy for prostate carcinoma causes persistent GI toxicity that is
      largely independent of the two dose schedules. The hypofractionated schedule is
      equivalent in efficacy to the conventional schedule.

PMID- 16965867
TI  - Multiple sclerosis, brain radiotherapy, and risk of neurotoxicity: the Mayo
      Clinic experience.
AB  - PURPOSE: The aim of this study was a retrospective assessment of neurotoxicity in
      patients with multiple sclerosis (MS) receiving external beam radiotherapy (EBRT)
      to the brain. METHODS AND MATERIALS: We studied 15 consecutively treated patients
      with MS who received brain EBRT. Neurologic toxicity was assessed with the Common
      Toxicity Criteria v.3.0. RESULTS: Median follow-up for the 5 living patients was
      6.0 years (range, 3.3-27.4 years). No exacerbation of MS occurred in any patient
      during EBRT. Five patients had Grade 4 neurologic toxicity and 1 had possible
      Grade 5 toxicity. Kaplan-Meier estimated risk of neurotoxicity greater than Grade
      4 at 5 years was 57% (95% confidence interval, 27%-82%). Toxicity occurred at
      37.5 to 54.0 Gy at a median of 1.0 year (range, 0.2-4.3 years) after EBRT.
      Univariate analysis showed an association between opposed-field irradiation of
      the temporal lobes, central white matter, and brainstem and increased risk of
      neurotoxicity (p < 0.04). Three of 6 cases of toxicity occurred in patients
      treated before 1986. CONCLUSIONS: External beam radiotherapy of the brain in
      patients with MS may be associated with an increased risk of neurotoxicity
      compared with patients without demyelinating illnesses. However, this risk is
      associated with treatment techniques that may not be comparable to modern,
      conformal radiotherapy.

PMID- 16965868
TI  - Phase I trial of gefitinib with concurrent radiotherapy and fixed 2-h gemcitabine
      infusion, in locally advanced pancreatic cancer.
AB  - PURPOSE: Pancreatic cancers are resistant to radiotherapy (RT) and current
      chemotherapy agents. Epidermal growth factor receptor is overexpressed in
      pancreatic cancer, and in vitro studies have shown that epidermal growth factor
      receptor inhibitors can overcome radio- and chemoresistance. The aim of the study
      was to determine whether the addition of gefitinib to RT and gemcitabine for
      patients with locally advanced pancreatic carcinoma (LAPC) was feasible and safe.
      METHODS AND MATERIALS: Eighteen patients with pathologically proven LAPC, based
      on major vascular invasion based on helical computed tomography (CT) and
      endoscopic ultrasound, were entered into the study. The targeted irradiated
      volume included the tumor and 2-cm margin. Prophylactic irradiation of regional
      nodes was not allowed. Patients with >500 cm(3) of planning tumor volume were
      excluded. An initial cohort of 6 patients was treated with RT (45 Gy/25
      fractions/5 weeks) plus concomitant gefitinib (250 mg/day). Successive cohorts of
      patients received 100, 150, and 200 mg/m(2)/day of gemcitabine in a 2-h infusion
      over Weeks 1, 2, 3, 4, and 5 with gefitinib (250 mg/day) and RT. Gefitinib was
      continued after RT until progression. A pharmacodynamic study of angiogenic
      markers was also performed to evaluate a possible antiangiogenic effect. RESULTS:
      There were no dose-limiting toxicities. Common toxicities were mild neutropenia,
      asthenia, diarrhea, cutaneous rash and nausea/vomiting. The median (95%
      confidence interval [CI]) progression-free survival was 3.7 (95% CI = 1.9-5.5)
      months, and the median overall survival was 7.5 (95% CI = 5.2-9.9) months. No
      significant reduction of vascular endothelial growth factor and interleukin-8 was
      observed after treatment. CONCLUSION: Our results support that the combination of
      gefitinib, RT, and gemcitabine has an acceptable toxicity but with modest
      activity in LAPC.

PMID- 16965869
TI  - Do prostate cancer patients want to choose their own radiation treatment?
AB  - PURPOSE: The aims of this study were to investigate whether prostate cancer
      patients want to be involved in the choice of the radiation dose, and which
      patients want to be involved. METHODS AND MATERIALS: This prospective study
      involved 150 patients with localized prostate cancer treated with three
      dimensional conformal radiotherapy. A decision aid was used to explain the
      effects of two alternative radiation doses (70 and 74 Gy) in terms of cure and
      side effects. Patients were then asked whether they wanted to choose their
      treatment (accept choice), or leave the decision to the physician (decline
      choice). The treatment preference was carried out. RESULTS: Even in this older
      population (mean age, 70 years), most patients (79%) accepted the option to
      choose. A lower score on the designations Pre-existent bowel morbidity, Anxiety,
      Depression, Hopelessness and a higher score on Autonomy and Numeracy were
      associated with an increase in choice acceptance, of which only Hopelessness held
      up in multiple regression (p < 0.03). The uninformed participation preference at
      baseline was not significantly related to choice acceptance (p = 0.10).
      CONCLUSION: Uninformed participation preference does not predict choice behavior.
      However, once the decision aid is provided, most patients want to choose their
      treatment. It should, therefore, be considered to inform patients first and ask
      participation preferences afterwards.

PMID- 16965870
TI  - Long-term outcome of patients treated by radiation therapy alone for salivary
      gland carcinomas.
AB  - PURPOSE: To review a single-institution experience with the management of
      salivary gland cancers treated by radiation alone. METHODS AND MATERIALS: Between
      1960 and 2004, 45 patients with newly diagnosed salivary gland carcinomas were
      treated with definitive radiation to a median dose of 66 Gy (range, 57-74 Gy).
      Distribution of T-stage was: 24% T1, 18% T2, 31% T3, and 27% T4. Histology was:
      14 mucoepidermoid (31%), 10 adenocarcinoma (22%), 8 adenoid cystic (18%), 4
      undifferentiated (9%), 4 acinic (9%), 2 malignant mixed (4%), 2 squamous (4%),
      and 1 salivary duct carcinoma (2%). No patient had clinical or pathologic
      evidence of lymph node disease. Median follow-up was 101 months (range, 3-285
      months). RESULTS: The 5-year and 10-year rate estimates of local control were 70%
      and 57%, respectively. A Cox proportional hazard model identified T3-4 disease (p
      = 0.004) and radiation dose lower than 66 Gy (p = 0.001) as independent
      predictors of local recurrence. The 10-year overall survival and distant
      metastasis-free rates were 46% and 67%, respectively. CONCLUSION: Radiation
      therapy alone is a reasonable alternative to surgery in the definitive management
      of salivary gland cancers and results in long-term survival in a significant
      proportion of patients. Radiation dose in excess of 66 Gy is recommended.

PMID- 16965871
TI  - Radioimmunotherapy for non-Hodgkin's lymphoma: a review for radiation
      oncologists.
AB  - PURPOSE: The aim of this study was to review advances in radioimmunotherapy (RIT)
      for non-Hodgkin's lymphoma (NHL) and to discuss the role of the radiation
      oncologist in administering this important new form of biologically targeted
      radiotherapy. METHODS AND MATERIALS: A review of articles and abstracts on the
      clinical efficacy, safety, and radiation safety of yttrium Y 90 (90Y) ibritumomab
      tiuxetan (Zevalin) and iodine I 131 tositumomab (Bexxar) was performed. RESULTS:
      The clinical efficacy of RIT in NHL has been shown in numerous clinical trials of
      90Y ibritumomab tiuxetan and 131I tositumomab. Both agents have produced
      significant responses in patients with low-grade, follicular, or transformed NHL,
      including patients with disease that had not responded or had responded poorly to
      previous chemotherapy or immunotherapy. Reversible toxicities such as
      neutropenia, thrombocytopenia, and anemia are the most common adverse events with
      both agents. CONCLUSIONS: Radioimmunotherapy is safe and effective in many
      patients with B-cell NHL. 90Y ibritumomab tiuxetan and 131I tositumomab can
      produce clinically meaningful and durable responses even in patients in whom
      chemotherapy has failed. Treatment with RIT requires a multispecialty approach
      and close communication between the radiation oncologist and other members of the
      treatment team. The radiation oncologist plays an important role in treating
      patients with RIT and monitoring them for responses and adverse events after
      treatment.

PMID- 16965872
TI  - Case-matched comparison of contemporary radiation therapy to surgery in patients
      with locally advanced prostate cancer.
AB  - PURPOSE: Few studies critically compare current radiotherapy techniques to
      surgery for patients with locally advanced prostate cancer, despite an urgent
      need to determine which approach offers superior cancer control. Our objective
      was to compare rates of biochemical relapse-free survival (BFS) and surrogates of
      disease specific survival among men with high risk adenocarcinoma of the prostate
      as a function of treatment modality. METHODS AND MATERIALS: Retrospective data
      from 409 men with prostate-specific antigen (PSA) > or =10 or Gleason 7-10 or
      Stage > or =T2b cancer treated uniformly at one university between March 1988 and
      December 2000 were analyzed. Patients had undergone radical prostatectomy (RP),
      brachytherapy implant alone (BTM), or external beam radiotherapy with
      brachytherapy boost with short-term neoadjuvant and adjuvant androgen deprivation
      therapy (BTC). From the total study population a 1:1 matched-cohort analysis (208
      patients matched via prostate-specific antigen, Gleason score) comparing RP with
      BTC was performed as well. RESULTS: Estimated 4-year BFS rates were superior for
      patients treated with BTC (BTC 72%, BTM 25%, RP 53%; p < 0.001). Matched analysis
      of BTC vs. RP confirmed these results (BTC 73%, BTM 55%; p = 0.010). Relative
      risk (RR) of biochemical relapse for BTM and BTC compared with RP were 2.92 (1.95
      4.36) and 0.56 (0.36-0.87), (p < 0.001, p = 0.010). RR for BTC from the matched
      cohort analysis was 0.44 (0.26-0.74; p = 0.002). CONCLUSIONS: High-risk prostate
      cancer patients receiving multimodality radiation therapy (BTC) display
      apparently superior BFS compared with those receiving surgery (RP) or
      brachytherapy alone (BTM).

PMID- 16965873
TI  - Comparison of normal tissue pharmacokinetics with 111In/90Y monoclonal antibody
      m170 for breast and prostate cancer.
AB  - PURPOSE: Radioactivity deposition in normal tissues limits the dose deliverable
      by radiopharmaceuticals (RP) in radioimmunotherapy (RIT). This study investigated
      the absorbed radiation dose in normal tissues for prostate cancer patients in
      comparison to breast cancer patients for 2 RPs using the monoclonal antibody
      (MAb) m170. METHODS AND MATERIALS: 111In-DOTA-glycylglycylglycyl-l-p
      isothiocyanatophenylalanine amide (GGGF)-m170 and 111In-1,4,7,10
      tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) 2-iminothiolane (2IT)
      m170, representing the same MAb and chelate with and without a cleavable linkage,
      were studied in 13 breast cancer and 26 prostate cancer patients. Dosimetry for
      90Y was calculated using 111In MAb pharmacokinetics from the initial imaging
      study for each patient, using reference man- and patient-specific masses.
      RESULTS: The reference man-specific radiation doses (cGy/MBq) were not
      significantly different for the breast and the prostate cancer patients for both
      RPs in all but one tissue-RP combination (liver, DOTA-2IT). The patient-specific
      doses had differences between the groups most of which can be related to weight
      differences. CONCLUSIONS: Similar normal tissue doses were calculated for two
      groups of patients having different cancers and genders. This similarity combined
      with continued careful analysis of the imaging data might allow the use of higher
      starting doses in early phase RIT studies.

PMID- 16965874
TI  - Is the type of test used for mass colorectal cancer screening a determinant of
      compliance? A cluster-randomized controlled trial comparing fecal occult blood
      testing with flexible sigmoidoscopy.
AB  - BACKGROUND: The efficacy of colorectal cancer screening has been proved, and
      three different screening tests are recommended by international guidelines: the
      faecal occult blood test, flexible sigmoidoscopy and colonoscopy. While the
      effectiveness of a screening program depends on the compliance obtained, the role
      of the type of test on compliance has not yet been sufficiently studied. AIMS: To
      measure the effect of the type of screening test used, i.e. faecal occult blood
      test or flexible sigmoidoscopy, on the compliance to colorectal cancer screening
      programs. SUBJECTS AND METHODS: A cluster-randomized two-arm trial was conducted.
      We randomly assigned 20 GP's practices that had an average of 150 patients
      between 50 and 74 years old. RESULTS: 1449 individuals were referred to faecal
      occult blood test and 1538 to flexible sigmoidoscopy. The faecal occult blood
      test obtained higher compliance: 17.2% (95%CI 12.5-25.7) versus 7.0% (95%CI 5.7
      9.0). The socio-economic status was an effect modifier of the test type: the
      effect of the type of test was smaller in low socioeconomic classes. CONCLUSIONS:
      The type of screening test used for colorectal cancer is a determinant of
      participation. In a low compliance area, better compliance will result from
      offering the faecal occult blood test than from the flexible sigmoidoscopy.

PMID- 16965875
TI  - Delay of treatment is associated with advanced stage of rectal cancer but not of
      colon cancer.
AB  - BACKGROUND: Dukes' stage is the most important predictor of prognosis of
      colorectal cancer, but the association between delay of treatment (DT) and Dukes'
      stage is still controversial. METHODS: From 1 January 2001 to 31 July 2002, we
      conducted a population-based prospective observational study based on 733 Danish
      colorectal cancer patients. DT was determined through questionnaire-interviews,
      and Dukes' stage was obtained from medical records and pathological forms. DT was
      classified into three groups: short (0-60 days), intermediate (61-150 days) and
      long (>150 days) DT. Dukes' stage was classified into two groups: non-advanced
      (Dukes' stage A or B) and advanced (Dukes' stage C or D) cancer. Using relative
      risk (RR) the association between DT and stage was estimated, with short delay as
      the reference group. RESULTS: The RR of advanced cancer was 1.0 (95% confidence
      intervals (CI): 0.8-1.3) for colon cancer patients with an intermediate DT, and
      1.1 (95% CI: 0.9-1.4) for patients with a long DT. For rectal cancer patients the
      RR of advanced cancer was 1.9 (95% CI: 1.1-3.1) for patients with an intermediate
      DT and 2.1 (95% CI: 1.3-3.4) for patients with a long DT. CONCLUSION: DT was
      strongly associated with advanced stage of rectal cancer, but not of colon
      cancer.

PMID- 16965876
TI  - Sub-diagnostic psychiatric comorbidity in alcoholics.
AB  - BACKGROUND: Psychiatric comorbidity in alcohol use disorders is clearly
      established, however most studies ignore data on psychiatric symptom counts that
      do not meet criteria for a diagnosis. We examined psychiatric symptom counts and
      psychological measures in the domains of anxiety, mood and externalizing
      pathology in 48 long-term abstinent alcoholics (LTAA) compared to 48 age/gender
      comparable light/non-drinking controls (NC). METHODS: Continuous measures of
      pathology (i.e., symptoms counts and psychological assessments) in each domain
      were compared between groups for: (1) all study participants, (2) excluding
      individuals with a lifetime psychiatric diagnosis in the domain, and (3)
      excluding individuals with a current psychiatric diagnosis in the domain.
      RESULTS: Psychiatric symptom counts and psychological pathology were greater in
      LTAA than NC. The differences between groups on these measures were not reduced
      by removal of individuals with lifetime or current diagnoses. CONCLUSIONS: The
      bulk of the difference between LTAA and NC in psychiatric illness was carried by
      sub-diagnostic psychopathology. In comparison to the limited view provided by
      using only symptomatology that meets criteria for a diagnosis, the use of
      continuous measures of psychiatric symptomatology and psychological abnormality
      yields a much more accurate picture of psychiatric illness co-occurring with
      alcoholism.

PMID- 16965878
TI  - Effect of Ocimum sanctum Linn. on cardiac changes in rats subjected to chronic
      restraint stress.
AB  - Male Wistar rats were subjected to chronic restraint stress (CRS; 6 h/day for 21
      days) alone or along with either hydroalcoholic extract of Ocimum sanctum (Os;
      100 mg/kg; orally) or MK-801, an NMDA receptor antagonist (0.3 mg/kg; i.p.). In
      the rats subjected to only CRS, plasma cAMP level was significantly raised on day
      21, with no significant change in plasma corticosterone level. There was a
      significant (p < 0.05) fall in myocardial glutathione level, along with a
      significant (p < 0.05) rise in myocardial superoxide dismutase (SOD) and catalase
      activities, while light microscopy showed evidence of myocardial edema. Both Os
      and MK-801 significantly prevented the CRS-induced rise in plasma cAMP level,
      myocardial SOD and catalase activities as well as the light microscopic changes
      in the myocardium. This study revealed that Ocimum sanctum protects rat heart
      from chronic restraint stress induced changes, through its central effect.

PMID- 16965879
TI  - Cause of death and drug use pattern in deceased drug addicts in Sweden, 2002
      2003.
AB  - Compared with their contemporaries, individuals abusing illicit drugs suffer a
      higher risk of premature death. In Sweden, a simple protocol for registration of
      fatalities among abusers of alcohol, pharmaceuticals, illicit drugs, or other
      substances, has been used by the forensic pathologists since 2001. This routine
      was introduced to allow for an evaluation of the cause and manner of death, and
      patterns of abuse among different groups of abusers. We explored the data on drug
      abusers (i.e. abusers of illicit drugs) subjected to a forensic autopsy 2002
      2003. The Swedish forensic pathologists examined 10,273 dead victims during the
      study period and 7% (743/10,273) of the cases were classified as drug abusers.
      Toxicological analyses were carried out in 99% (736/743) and illicit drugs were
      detected in 70% (514/736) of these. On average, 3.8 substances (legal or illegal)
      were found per case. The most common substances were ethanol and morphine,
      detected in 43 and 35% of the cases, respectively. When exploring the importance
      of the different substances for the cause of death, we found that the detection
      of some substances, such as fentanyl and morphine, strongly indicated a
      poisoning, whereas certain other substances, such as benzodiazepines more often
      were incidental findings. In total, 50% (372/743) died of poisoning, whereas only
      22% (161/743) died of natural causes. Death was considered to be directly or
      indirectly due to drug abuse in 47% (346/743), whereas evidence of drug abuse was
      an incidental finding in 21% (153/743) or based on case history alone in 33%
      (244/743). We believe that this strategy to prospectively categorize deaths among
      drug addicts constitutes a simple means of standardizing the surveillance of the
      death toll among drug addicts that could allow for comparisons over time and
      between countries.

PMID- 16965880
TI  - Individualizing characteristics of footprints in Gujjars of North India--forensic
      aspects.
AB  - Careful examination of foot impressions can provide important evidences and clues
      in a crime scene investigation. The present study is conducted on a cross
      sectional sample of 1040 adult male Gujjars inhabiting the sub-Himalayan region
      of North India. The study describes the utility of individualizing
      characteristics of footprints in forensic examinations. Various features of the
      toes, humps in the toe line, phalange marks, flatfoot condition, pits, cracks,
      corns, etc., were studied. Frequency of some of these characters has also been
      recorded. The frequency of the tibialis-type foot is the highest, followed by
      fibularis-type, then intermediate-type and midularis-type is found to be least
      frequent among the sample. Three humps have been found most often in footprints,
      followed by two humps, four humps, and then five humps and one hump are found to
      be least frequent. Flatfoot condition is found to be present in 1.54% of the
      sample population and the trait also shows bilateral variation. Phalange marks,
      crease marks, pits, deformity, etc., are also demonstrated with suitable examples
      in the present population. These characteristic features can provide useful clues
      to establish personal identity whenever complete or partial footprints are
      recovered at the crime scene and can help in including or excluding the possible
      presence of individual at the scene of crime.

PMID- 16965881
TI  - A boy who is an amazing artist.

PMID- 16965882
TI  - Contrast-enhanced MR 3D angiography in the assessment of brain AVMs.
AB  - BACKGROUND AND PURPOSE: Digital subtraction angiography (DSA) is the current
      reference standard for the diagnosis, assessment, and management of brain
      arteriovenous malformations (AVMs). The purpose of this study was to compare the
      diagnostic utility of three-dimensional (3D) time-of-flight (TOF) magnetic
      resonance angiography (MRA) and contrast-enhanced 3D MRA in patients with
      intracranial arteriovenous malformations (AVMs) in different sizes and locations.
      The AVM diagnosis was proved via DSA and almost half of the patients had also
      hematoma. MATERIALS AND METHODS: Two radiologists, experienced on neurovascular
      imaging and independent from each other, retrospectively reviewed two MRA
      techniques and DSA with regard to the assessment of feeding arteries, AVM nidus,
      and venous drainage patterns on 20 patients with 23 examinations by scoring
      system. Disagreements were resolved by consensus. RESULTS: An excellent agreement
      between contrast-enhanced MRA and DSA was found in order to assess the numbers of
      arterial feeders and draining veins (Spearman r=0.913, P<0.001). The average
      scores in contrast-enhanced MRA for feeders, nidi, and drainers were respectively
      2.26, 2.69, and 2.48, while in TOF-MRA they are 1.96, 1.35, and 0.89,
      respectively. CONCLUSION: Compared to TOF-MRA, 3D contrast-enhanced MRA is useful
      for visualization by subtraction technique of malformation components presented
      by hematoma or by haem product. On the other hand, for the cases presented by
      slow or complex flow that is especially in around or nidi or around the venous
      portion is also advantageous because of the independence from flow-related
      enhancement. Therapeutic effects were clearly demonstrated in three follow-up
      patients. A major limitation of this technique is the low spatial resolution.
      Since there is such a limitation, arterial feeder of a case with micro-AVM is not
      detected by contrast-enhanced MRA and nidus for the same case was observed
      retrospectively. In this respect, we believe that 3D contrast-enhanced MRA is a
      less invasive and inexpensive angiographic tool, but not a safe substitute for
      DSA. Yet, it can be a beneficial supplement to DSA in patients with cerebral AVMs
      at both initial diagnosis and at follow-up processes after therapy.

PMID- 16965883
TI  - Accuracy of single phase contrast enhanced multidetector CT colonography in the
      preoperative staging of colo-rectal cancer.
AB  - AIM: The optimal acquisition time for staging colo-rectal carcinoma with a
      contrast enhanced multidetector CT colonography (CE CTC) has not yet been
      established. A dual phase with both arterial and portal venous acquisition has
      been proposed. The purpose of our study is to assess the value of single portal
      venous phase CE CTC in the preoperative staging of colo-rectal carcinoma.
      MATERIALS AND METHODS: Fifty two (30 M, 22 F; aged 35-82 years) consecutive
      patients with a histologically proven diagnosis of colo-rectal adenocarcinoma or
      a highly suspected colo-rectal cancer on conventional colonoscopy underwent a
      four-slice CE CTC. The procedure was performed 70s (portal phase) after the
      intravenous bolus (3 ml/s) administration of 120 ml iodinated non-ionic contrast
      agent (370 mg iodine/ml). Scans were performed using the following parameters:
      2.5mm beam collimation, pitch 1.25, 120 kV, 200 mAs, rotation time 0.75 s. Images
      were reconstructed with an effective thickness of 3.2mm at intervals of 1.6mm.
      Two radiologists independently evaluated the depth of tumour invasion into the
      colo-rectal wall (T), regional lymph node involvement (N), and extracolonic
      metastases (M). Disagreement was resolved by means of a consensus decision. The
      pathological results served as the standard of reference. Assessment was made of
      sensitivity, specificity and accuracy, as well as positive and negative
      predictive values were assessed. RESULTS: CE CTC correctly staged the pT of 52/56
      (93%) and the N of 40/56 (71%) lesions, as well as properly identifying 13/14
      (93%) extracolonic findings. CONCLUSION: The single portal venous phase CE CTC
      scanning protocol enables satisfactory preoperative assessment of T, N and M
      staging in patients with colo-rectal cancer.

PMID- 16965884
TI  - European Society of Urogenital Radiology (ESUR) guidelines on the safe use of
      iodinated contrast media.
AB  - Since 1996 the Contrast Media Safety Committee of the European Society of
      Urogenital Radiology (ESUR) has released 19 guidelines regarding safety in
      relation to the use of radiographic, ultrasonographic as well as magnetic
      resonance contrast media. The committee has covered both renal and non-renal
      adverse events as well as other aspects of contrast media. The present paper is
      an overview of the work accomplished over the last 10 years regarding
      radiographic iodinated contrast media.

PMID- 16965885
TI  - Patient education in Parkinson's disease: Formative evaluation of a standardized
      programme in seven European countries.
AB  - OBJECTIVE: To evaluate a newly developed education programme for Parkinson's
      disease (PD) patients. METHODS: The programme consisted of eight sessions and
      aimed at improving knowledge and skills related to self-monitoring, health
      promotion, stress management, depression, anxiety, social competence, and social
      support, all with special reference to PD. The programme was formatively
      evaluated in seven European countries (Spain, Finland, Italy, The Netherlands,
      United Kingdom, Estonia, Germany) with 151 patients diagnosed with idiopathic PD.
      The evaluation included patients' ratings of the comprehensibility and
      feasibility of the programme as well as mood ratings before and after each
      session. Patients also completed questionnaires at the beginning and end of the
      programme to explore possible changes in disease-related psychosocial problems,
      quality of life, and depression. RESULTS: The programme was feasible to run, and
      patients were able to understand its elements. Patients reported mood elevations
      following individual sessions and reduced disease-related psychosocial problems
      after completing the programme. There were no substantial differences in results
      between cultures. CONCLUSION: Patient education appears to have potential as a
      useful and feasible intervention, complementing medical treatment in PD. PRACTICE
      IMPLICATIONS: The present programme will soon be available in seven European
      languages and can be tested in different health care systems.

PMID- 16965886
TI  - The added value of assessing the 'most troublesome' symptom among patients with
      cancer in the palliative phase.
AB  - OBJECTIVE: In this study among patients with cancer in the palliative phase, we
      analysed whether assessing the symptom, which is causing the most trouble in the
      patient's every day life ('most troublesome' symptom) had added value apart from
      the presence and severity of symptoms, which are most commonly assessed in
      clinical practice. METHODS: Patients with cancer (lung, gastro-intestinal, breast
      cancer) in the palliative phase from two non-academic hospitals were included in
      the study. Using the Symptom Monitor tool, 10 physical symptoms were assessed
      with regard to presence and severity. The Symptom Monitor has an extra added item
      indicating as the 'most troublesome' symptom. This item was monitored to
      determine whether it had added value apart from the presence of symptoms and
      'most severe' symptom. The severity score on the indicated 'most troublesome'
      symptom was subtracted from the severity score of the 'most severe' symptom. The
      generated delta score of 0 indicated no added value, whereas a score of one or
      more indicated that the 'most troublesome' symptom would have been missed if not
      specifically asked for by the physician, because its severity was lower that the
      'most severe' symptom. RESULTS: One hundred and forty-six patients reported 590
      symptoms to be present. In total, 227 symptoms were reported as 'most severe'
      symptom (n = 138 patients). Among these, fatigue (n = 52) and pain (n = 24) were
      reported most frequently as 'most severe' symptom. In total, 134 patients
      indicated a symptom as 'most troublesome'. Fatigue (n = 33; 25%) and pain (n =
      22; 16%) were also indicated by most of these patients as the 'most troublesome'
      symptom. One hundred and fifty-two comparisons could be made between the 'most
      severe' and the 'most troublesome' symptom. In 102 (67%) of the comparisons
      assessing the 'most troublesome' symptom had no added value: the score for 'most
      severe' symptom did not differ from the score for the 'most troublesome' symptom
      revealing a delta score of 0. In 23 times (15%) of the 152 comparisons made, the
      delta score was 1 and in 27 (18%) of the comparisons the delta score was 2 or
      more indicating that assessing the 'most troublesome' symptom substantially had
      added value. CONCLUSION: In patients in the palliative phase of their disease,
      extra attention for the 'most troublesome' symptom is needed. In our study, in
      almost 1/3 of the cases, this symptom would have been missed the physicians
      attention if not specifically asked for. PRACTICE IMPLICATIONS: We recommend not
      only to assess the presence and severity of symptoms, but furthermore to assess
      the patient's 'most troublesome' symptom in addition.

PMID- 16965887
TI  - Treatment decision making in prostate cancer: patients' participation in complex
      decisions.
AB  - OBJECTIVE: (1) To explore to what degree prostate cancer (PC) patients felt they
      had participated in treatment decision making (TDM). (2) To determine whether
      perceived roles during TDM were associated with medical and sociodemographic
      variables. (3) To examine to what extent satisfaction with TDM was related to
      perceived role or medical and sociodemographic variables. METHODS: Patients
      (n=126) were recruited in hospitals and from the Dutch PC patient organization.
      The relationship between patients' role and stage of disease, treatment modality,
      age, social status and education was determined, as well as patients'
      satisfaction with TDM. RESULTS: Most patients felt they had participated in TDM
      (autonomous 18%, collaborative 60%). Older patients and those with advanced
      disease more frequently reported not having been involved in decision making.
      Satisfaction with TDM was related to age and role in TDM but not to stage of
      disease or treatment modality. Younger men were least content when they had not
      been involved in decision making. CONCLUSION: Patients' level of participation
      and satisfaction with TDM appears to be related to medical and sociodemographic
      variables. PRACTICE IMPLICATIONS: Satisfaction with TDM may be related to
      patients' age and assumed role. It is recommended to take this into account when
      planning treatment for prostate cancer patients.

PMID- 16965888
TI  - Patient willingness to take teriparatide.
AB  - OBJECTIVE: Teriparatide [rhPTH (1-34)] is an effective treatment for osteoporosis
      administered by daily subcutaneous injection. The objective of this study was to
      determine how much benefit women expect teriparatide to confer before agreeing to
      perform daily injections. METHODS: We recruited postmenopausal women who had
      recently undergone bone densitometry and were found to have either a T-score less
      than -2.5 at the hip or spine and/or had a fracture index (FI) of > or =6.
      Participants completed an adaptive conjoint analysis questionnaire to determine
      their treatment preferences. RESULTS: The study sample included 185 women, mean
      age 71 (range 46-90). An increasing number of subjects preferred rhPTH (1-34) as
      the efficacy of teriparatide increased, but most women demanded efficacy
      advantages greater than those demonstrated in clinical studies. We found no
      association between absolute fracture risk and preference for rhPTH (1-34);
      however, subjects with an excessively high perceived risk of future fracture were
      more likely to accept daily subcutaneous injections compared to subjects with a
      lower perceived risk of future fracture (40% versus 15%, p = 0.001). CONCLUSION:
      Our results suggest that most women demand benefits far greater than those
      conferred by rhPTH (1-34) in order to administer daily subcutaneous injections to
      decrease their future risk of fractures. PRACTICE IMPLICATIONS: Given the poor
      adherence for treatment of osteoporosis, and the choices older adults must make
      when paying for medications, development of novel treatment approaches should be
      based on older adults' treatment preferences.

PMID- 16965889
TI  - Groningen orthopaedic exit strategy: Validation of a support program after total
      hip or knee arthroplasty.
AB  - OBJECTIVE: Validation of the program theory of the Groningen orthopaedic exit
      strategy (GOES), a theory-driven program aiming to improve the rehabilitation of
      total hip and knee arthroplasty patients after shortened hospital stay. First
      part of the program theory is the action theory, hypothesising that the GOES
      treatment positively influences the mediating variables (self-efficacy, social
      support, pain-coping). The second part, the conceptual theory, hypothesis a
      positive relationship between these variables and the outcome variables (ADL
      functioning, physical activity behaviour, quality of life). METHODS: Patients
      were randomly assigned to the GOES or control groups. Questionnaires were used to
      assess mediating and outcome variables in 103 patients (50 GOES, 53 controls) pre
      operatively, and 6 and 26 weeks post-operatively. RESULTS: No difference was seen
      between the two groups in terms of changes between pre-operative and post
      operative mediating variables (action theory). Moderate-to-large correlations
      explaining reasonable amount of variance (22%, 25%, 56%) were found between the
      mediating and outcome variables (conceptual theory). CONCLUSION: The conceptual
      theory is supported; however, as the treatment did not influence the mediating
      variables (action theory), it has no added value in its current form. PRACTICE
      IMPLICATIONS: The treatment needs to be adjusted; it is discussed that
      individualised treatment could be more effective.

PMID- 16965890
TI  - Day dreams.

PMID- 16965891
TI  - Participation of family members in ward rounds: Attitude of medical staff,
      patients and relatives.
AB  - OBJECTIVE: To assess the attitude of medical staff, patients and their relatives
      to the presence of FMs in WRs. METHODS: This prospective study was performed in
      an Internal Medicine Department in Israel. WRs were conducted without (phase 1)
      and with (phase 2) the presence of FMs. Questionnaires were completed by staff
      members (N = 26, 23), patients (N = 26, 35) and FMs (N = 32, 40) during phases 1
      and 2, respectively. RESULTS: 82.6%, 96% and 96.7% of staff, patients and
      relatives, respectively, expressed a positive attitude towards the participation
      of FMs in WRs. Staff members became significantly more positive about the concept
      after having undergone the experience. Patients believed it contributed to a
      better understanding of their disease and FMs felt it provided them with an
      opportunity to participate in medical decision-making. CONCLUSION: Hospitalized
      patients would like their FMs to participate in WRs. Staff members were reluctant
      at first, but developed a more positive attitude towards the idea after the
      experience. PRACTICE IMPLICATIONS: Incorporating FMs into WRs is plausible,
      though adjustment of WRs' routine to the change will be needed. This move might
      increase patients' satisfaction from WRs.

PMID- 16965892
TI  - Predictors of general medical and psychological treatment use among a national
      sample of peacekeeping veterans with health problems.
AB  - We investigated general medical and psychological treatment use predictors among
      peacekeeping veterans with health problems, aiming to find those characteristics
      most associated with treatment use intensity (i.e., visit counts). One thousand
      one hundred and thirty-two male Canadian Forces peacekeeping veterans registered
      with Veterans Affairs for health problems were randomly recruited for a
      prospective national survey. Regression analyses for treatment use intensity
      controlled for age, total time deployed and health problems (covariates), and
      examined the incremental contribution of depression and post-traumatic stress
      disorder (PTSD) severity on health service use intensity. Results revealed that
      after controlling for covariates, the depression and PTSD model was associated
      with increased medical and psychological treatment use intensity. Medical use
      intensity was significantly predicted by married status, greater depression and
      health problems; psychological treatment use intensity was predicted by younger
      age, greater PTSD severity and health problems. This study highlights the
      importance of an integrated primary care-mental health service delivery model for
      veterans.

PMID- 16965893
TI  - Severe craniofacial malformations resulting from developmental exposure to
      dioxin.

PMID- 16965894
TI  - Games that "work": using computer games to teach alcohol-affected children about
      fire and street safety.
AB  - Unintentional injuries are a leading cause of death and disability for children.
      Those with developmental disabilities, including children affected by prenatal
      alcohol exposure, are at highest risk for injuries. Although teaching safety
      skills is recommended to prevent injury, cognitive limitations and behavioral
      problems characteristic of children with fetal alcohol spectrum disorder make
      teaching these skills challenging for parents and teachers. In the current study,
      32 children, ages 4-10, diagnosed with fetal alcohol syndrome (FAS) and partial
      FAS, learned fire and street safety through computer games that employed "virtual
      worlds" to teach recommended safety skills. Children were pretested on verbal
      knowledge of four safety elements for both fire and street safety conditions and
      then randomly assigned to one condition. After playing the game until mastery,
      children were retested verbally and asked to "generalize" their newly acquired
      skills in a behavioral context. They were retested after 1 week follow-up.
      Children showed significantly better knowledge of the game to which they were
      exposed, immediately and at follow-up, and the majority (72%) was able to
      generalize all four steps within a behavioral setting. Results suggested that
      this is a highly effective method for teaching safety skills to high-risk
      children who have learning difficulties.

PMID- 16965895
TI  - Preparation of prefabricated vascularized bone graft with neoangiogenesis by
      combination of autologous tissue and biodegradable materials.
AB  - Prefabricated vascularized bone grafts have previously been prepared by combining
      an autologous vessel bundle with auto-particulate cancellous bone and marrow
      (PCBM) and a biodegradable membrane. Only small quantities of low-density
      vascularized bone tissue have been formed using this method. The authors of the
      present study combined beta-tricalcium phosphate (beta-TCP), a biodegradable
      ceramic, with a prefabricated vascularized bone graft to augment osteogenesis. A
      saphenous vessel bundle from a rat was wrapped in a biodegradable membrane. Then,
      autologous PCBM was mixed with beta-TCP granules and packed into the rolled
      membrane. In the control group, beta-TCP was omitted. Bone formation was
      histologically assessed 6 and 9 weeks after implantation. The volume of newly
      formed bone tissue in the rolled membrane was greater in the presence of beta-TCP
      granules than in the control. Microvessels had formed throughout the new bone
      tissue. When a prefabricated vascularized bone graft was onlay-grafted to the
      femur of the same rat, the prefabricated vascularized bone graft directly fused
      to the cortical surface of the femur, with no intervening fibrous tissue. These
      findings suggest that beta-TCP in combination with PCBM enhances the volume and
      density of bone tissue in prefabricated vascularized bone grafts.

PMID- 16965896
TI  - Mandibular metastasis of nephroblastoma: a rare case.
AB  - Wilms' tumour (nephroblastoma) is a renal tumour that develops in childhood; it
      is one of the most common malignant tumours in children under 5 years old. Bone
      metastases are extremely rare in Wilms' tumour. Reported here is a patient who
      underwent nephrectomy for Wilms' tumour at the age of 2 years and presented with
      a jawbone mass in her left mandible 9 months later.

PMID- 16965897
TI  - Detection of serum Cyfra 21-1 in patients with primary oral squamous cell
      carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) is the most common malignant tumour in the
      oral and maxillofacial region, and has a poor prognosis. Cyfra 21-1 is a useful
      tumour marker for squamous cell carcinoma, but the clinical value of Cyfra 21-1
      in OSCC has not been confirmed. In order to investigate the diagnostic and
      prognostic value of serum Cyfra 21-1 in primary OSCC patients, the preoperative
      serum Cyfra 21-1 concentration of 100 OSCC patients and 56 healthy subjects was
      detected by enzyme-linked immunosorbent assay (ELISA). The cut-off value was
      calculated with a receiver operating characteristic (ROC) curve, and prognostic
      analysis was performed using the Kaplan-Meier method and Cox regression models.
      The preoperative serum Cyfra 21-1 concentration in OSCC patients (1.18+/-1.20
      microg/L) was significantly higher (t=6.585, P<0.001) than that in healthy
      subjects (0.40+/-0.16 microg/L). With a cut-off value of 0.65 microg/L, the
      diagnostic sensitivity and specificity was 0.570 and 0.964, respectively. There
      was significant correlation with tumour recurrence and survival rate: the higher
      the serum Cyfra 21-1; the higher the tumour recurrence rate and lower the
      survival rate. Serum Cyfra 21-1 was an independent prognostic factor for OSCC
      using univariate and multivariate Cox models.

PMID- 16965898
TI  - Causes and distribution of facial fractures in a group of South African children
      and the value of computed tomography in their assessment.
AB  - The cases of 107 paediatric patients aged 0-12 years were retrospectively
      reviewed. The patients presented with facial trauma and both plain radiographs
      and computed tomography (CT) scans had been ordered. Sixty-five per cent of
      facial fractures were missed in radiography, but revealed on CT; fractures of the
      maxilla, the zygoma and the orbit were most frequently missed in radiography.
      Pedestrian motor vehicle accidents were the most frequent cause of facial
      fractures (37%), followed by passenger motor vehicle accidents (22%). In contrast
      with other studies reporting the mandible as the most frequent facial fracture
      site, the most common fracture sites in this study, in descending order of
      frequency, were the orbit, the frontal bone and the maxilla.

PMID- 16965899
TI  - Reconstruction of orbital wall defects with calcium phosphate cement: clinical
      and histological findings in a sheep model.
AB  - The aim of this pilot study was to investigate the potential of calcium phosphate
      cement in the treatment of orbital wall defect fractures in an adult sheep model,
      and to compare this alloplastic material to autologous calvaria split-bone
      grafts. Clinical, volumetric and histological examinations were carried out of
      both reconstruction materials. The use of cement made intraoperative corrections
      easier to perform, and increased the precision of reconstruction of the orbital
      volume. This material also proved to be osseoconductive. The two materials were
      used successfully in combination. Regions of most intensive remodelling were the
      anterior orbital floor and the adjacent orbital rim. The preliminary results of
      this study demonstrate the potential of calcium phosphate cement as a useful
      biomaterial in the reconstruction of the anterior orbital region. Further animal
      and clinical trials are necessary to investigate its ability as a carrier for
      mediators where bone healing requires influence or support.

PMID- 16965900
TI  - Myokymia (fasciculation) of the tongue as a unique presentation of mucoepidermoid
      carcinoma.
AB  - Neural invasion is a relatively common feature of squamous cell carcinomas of the
      head and neck and malignant salivary gland tumours. The symptoms depend on the
      location and the particular nerves involved, and include pain, anaesthesia,
      paraesthesia and cranial nerve palsy. The present case appears to be unique. A
      mucoepidermoid carcinoma showed evidence of neural involvement and presented with
      nerve stimulation inducing myokymia, rather than nerve destruction, which is the
      usual consequence of tumoral nerve invasion.

PMID- 16965901
TI  - Nodular fasciitis in the orofacial region.
AB  - Nodular fasciitis (NF) is a benign, reactive proliferation of fibroblasts in
      subcutaneous tissues which commonly occurs in the deep fascia. It can only be
      diagnosed by histopathological examination of a biopsy. A total of 23 orofacial
      NF patients was analysed, including those reported in the English language
      literature and six new patients from the files of this hospital. All patients
      were treated between 1994 and 2005. The reported lesions were located in cheek
      masseter muscle, parotid gland, upper neck, upper gingiva and body of mandibular.
      The clinical and histological features and differential diagnoses are discussed.
      All lesions were removed under general or local anaesthesia and no recurrence of
      the lesions was found.

PMID- 16965902
TI  - Trans-sinusal maxillary distraction for correction of midfacial hypoplasia: long
      term clinical results.
AB  - Maxillary distraction osteogenesis is indicated in severe angle class III
      malocclusions, and severe maxillary hypoplasia among some cleft patients and
      other craniofacial deformities. Twenty patients, aged 8-48 years (mean 17.8+/
      10.5 SD) with maxillary and midfacial hypoplasia were treated. The follow-up
      period was 13-65 months (mean 35+/-16.3 SD). A trans-sinusal maxillary distractor
      was placed intraorally at each side of the maxilla. The distraction vector was
      predicted using specialist software, and was transferred to the patients using
      stereolithographic models and individual templates. A (high) Le Fort I type
      osteotomy was performed. The amount of activation varied from 8 to 17.5 mm (mean
      13.1+/-2.9 SD). Soft and hard tissue formation resulted in complete healing
      across the distraction gaps. The distractors are almost completely submerged, and
      can be left in place as long as necessary to avoid relapse. Wit's appraisal was
      used to measure the stability of the long-term distraction results. Results up to
      5 years after distraction showed considerable maxillary advancement with long
      term stability. Ongoing growth of the facial skeleton must be considered when
      distraction osteogenesis is chosen in growing patients.

PMID- 16965903
TI  - Mucosal keratinocyte isolation: a short comparative study on thermolysin and
      dispase.
AB  - New techniques for reconstructing large defects of the floor of the mouth include
      the use of cultured mucosal substitutes. The purpose of this study was to compare
      dispase and thermolysin for keratinocyte isolation. Keratinocyte yield per
      surface area of rabbit buccal mucosa was assessed by histology, cytokeratin 13
      (CK13) staining, seeding efficiency analysis and cell diameter quantification.
      Surface areas of cultured mucosa were calculated. Histology showed that treatment
      by thermolysin resulted in incomplete separation of epidermis from dermis. Also,
      the absolute number of keratinocytes/cm(2) isolated mucosa, cell yield, cell size
      and seeding efficiencies was higher in the dispase group. A 3.45-fold larger
      graft could be reconstituted using dispase. The use of dispase, rather than
      thermolysin, to isolate cells from buccal mucosa is concluded to be favourable.

PMID- 16965904
TI  - Osteosclerotic bone dysplasia (melorheostosis) of the mandible.
AB  - Melorheostosis is a linear bone dysplasia of unknown origin that may be
      associated with soft-tissue alterations. Although any part of the skeleton can be
      affected, this condition is rarely observed in the craniofacial region. Only
      seven cases of melorheostosis with craniofacial involvement have been reported
      and cranial manifestation only is even rarer. To the authors' knowledge,
      manifestation in the mandible only has not yet been documented. A patient with
      isolated melorheostosis of the mandible with characteristic symptomatic bone pain
      is presented. The clinical, radiological and histological findings are described
      and possible therapeutic options are discussed.

PMID- 16965905
TI  - Resistance to imipenem and zinc in clinical isolates of Pseudomonas aeruginosa.

PMID- 16965906
TI  - Accuracy and reliability of physical signs in the diagnosis of pleural effusion.
AB  - Although pleural effusion is a common disorder among patients presenting with
      respiratory symptoms, there is limited evidence on the accuracy and reliability
      of symptoms and signs for the diagnosis of pleural effusion. In our study,
      conducted at a rural hospital in India, two physicians, blind to history and
      chest radiograph findings, and to each other's results, independently evaluated
      278 patients (196 men), aged 12 and older, admitted with respiratory symptoms. We
      did a blind and independent comparison of physical signs (asymmetric chest
      expansion, vocal fremitus, percussion note, breath sounds, crackles, vocal
      resonance and auscultatory percussion) with the reference standard (chest
      radiograph). We measured diagnostic accuracy by computing sensitivity,
      specificity, and likelihood ratios (LRs), and inter-observer reliability by using
      kappa (kappa) statistic. We performed multivariate analysis to identify the
      clinical signs that independently predict pleural effusion. The prevalence of
      pleural effusion was 21% (57/278). The LRs of positive signs ranged from 1.48 to
      8.14 and their 95% confidence intervals (CIs) excluded 1. Except for pleural rub,
      the LRs for negative signs ranged between 0.13 and 0.71. The interobserver
      agreement was excellent for chest expansion, vocal fremitus, percussion and
      breath sounds (kappa 0.84-0.89) and good for vocal resonance, crackles and
      auscultatory percussion (kappa 0.68-0.78). The independent predictors of pleural
      effusion were asymmetric chest expansion (odds ratio [OR] 5.22, 95% CI 2.06
      13.23), and dull percussion note (OR 12.80, 95% CI 4.23-38.70). For the final
      multivariate model, the area under receiver operating characteristic curve (ROC
      curve) was 0.88. In conclusion, our data suggest that physical signs may be
      helpful to rule out but not rule in pleural effusion.

PMID- 16965907
TI  - Leukotriene E(4) in urine in patients with asthma and COPD--the effect of smoking
      habit.
AB  - Leukotriene E(4) (LTE(4)) is implicated in asthma pathophysiology and possibly in
      chronic obstructive pulmonary disease (COPD) as one of the causes of persistent
      bronchoconstriction and mucus hypersecretion. Cigarette smoking stimulates
      cysteinyl leukotrienes (CysLTs) production. We investigated whether LTE(4) is
      equally increased in asthma and COPD and whether smoking significantly affects
      LTE(4) levels. Secondary outcomes involved correlations with inflammatory and
      functional parameters. We studied 40 patients with COPD [20 smokers], 40
      asthmatics [20 smokers] and 30 healthy subjects [15 smokers]. Spirometry (FEV(1)%
      pred., FEV(1)/FVC) was performed, urine was collected for measurement of LTE(4)
      and creatinine, induced sputum was collected for differential cell counts and
      serum for ECP. LTE(4)/creatinine levels (pg/mg) [mean (sd)] were increased in
      asthmatic patients compared to COPD and controls, [125.6(54.5) vs. 54.5(19) vs.
      55.9(18.9)pg/mg, respectively, P<0.0001 for asthma]. Smoking significantly
      affects LTE(4) levels only in asthmatic patients [164 (48) vs. 87 (26.3),
      P<0.0001 for smokers]. The only significant correlation was between eosinophils
      in induced sputum and LTE(4)/creatinine levels in asthmatics. In conclusion,
      patients with asthma presented higher LTE(4) values compared to normals and
      patients with COPD. Smoking significantly affects LTE(4) values only in
      asthmatics indicating a different underlying CysLTs inflammatory process in this
      condition.

PMID- 16965908
TI  - Detection of organics using porphyrin embedded nanoporous organosilicas.
AB  - Molecularly imprinted polymers and silica have been studied as receptor binding
      site mimics for use in a wide range of separation, catalysis, and detection
      applications employing transduction mechanisms including conductometric,
      amperometric, and capacitance. Porphyrins are also well known as sensor
      components due to the extreme sensitivity of their spectrophotometric
      characteristics to changes in their immediate environment. We have developed
      periodic mesoporous organosilicas (PMO) which incorporate a porphyrin into the
      material for use as an optical indicator of target binding. This material
      combines the stability, selectivity, and high density of binding sites
      characteristic of the molecularly imprinted PMO with the sensitivity and
      selectivity of the porphyrin. We demonstrate binding of p-nitrophenol, p-cresol,
      2,4,6-trinitrotoluene, and RDX by the porphyrin-embedded PMOs with selective
      adsorption of TNT over the other analytes. In addition, the binding of each of
      the organics by the PMO results in unique changes in the spectrophotometric
      characteristics of the incorporated porphyrin. These changes can be observed by
      visual inspection or through the use of fluorescence spectra collected in 96-well
      format.

PMID- 16965909
TI  - Role of radiotherapy and chemotherapy in the risk of secondary leukaemia after a
      solid tumour in childhood.
AB  - The aim of this study was to determine the therapy-related risk factors for the
      occurrence of leukaemia after childhood solid cancer. Among 4204 3-year survivors
      of a childhood cancer treated in eight French and British centres before 1986, 11
      patients developed leukaemia as a second malignant neoplasm (SMN). Compared with
      the leukaemia incidence in the general French and British populations, the
      standardised incidence ratio (SIR) of leukaemia was 7.8 (95% CI 4.0-13.4). It
      decreased from 20.3 (95% CI 8.3-41.2) during the first years of follow-up, to 2.2
      (95% CI 0.1-9.7) between 10 and 20 years, but rose again to 14.8 (95% CI 3.7
      38.3) 20 or more years after the first cancer. Radiotherapy appeared to increase
      the risk of leukaemia at moderate weighted doses to active bone marrow; the
      relative risk (RR) was 4.2 (95% CI 0.8-20.7) for doses ranging from 3 to 6.6 Gy.
      A greater RR was observed for epipodophyllotoxins and for vinca alkaloids. No
      specific type of first malignant neoplasm (FMN) was found to lead to a higher
      risk of secondary leukaemia. Epipodophyllotoxins and vinca alkaloids at high
      doses and moderate weighted radiation doses to active bone marrow may contribute
      independently to an increased risk of leukaemia for patients treated for
      childhood cancer. Our results suggest that the long-term risk of secondary
      leukaemia could be higher than previously reported.

PMID- 16965910
TI  - Alterations in the p53 pathway and prognosis in advanced ovarian cancer: a multi
      factorial analysis of the EORTC Gynaecological Cancer group (study 55865).
AB  - PURPOSE: The study was designed to determine independent prognostic variables in
      suboptimally debulked advanced ovarian cancer patients entered in the randomised
      phase III study EORTC 55865. EXPERIMENTAL DESIGN: Retrospectively collected
      paraffin blocks from 169 patients with stages IIb-IV epithelial ovarian cancer,
      taken at primary debulking surgery, were analysed. All patients were treated with
      cyclophosphamide and cisplatin (CP), and followed up for a median of 10 years.
      Expression of p53, bcl-2, P21, Ki-67 and HER-2 status was assessed by
      immunohistochemistry (IHC). RESULTS: Expression of p21, a downstream effector of
      the p53 gene, was found to be a favourable prognostic factor for survival (HR
      0.58, CI 0.36-0.94, p=0.025) in addition to FIGO stage (HR 1.54, CI 1.08-2.21,
      p=or<0.02). For progression free survival (PFS), both p21 (HR 0.52) and Ki-67 (HR
      0.6) were significant factors. CONCLUSION: P21 overexpression is a positive
      prognostic factor for survival and PFS in advanced ovarian carcinoma with
      residual lesions of more than 1 cm.

PMID- 16965911
TI  - To predict progression-free survival and overall survival in metastatic renal
      cancer treated with sorafenib: pilot study using dynamic contrast-enhanced
      Doppler ultrasound.
AB  - INTRODUCTION: The objective of this study was to evaluate dynamic contrast
      enhanced Doppler ultrasound (DCE-US) with perfusion software (Vascular
      Recognition Imaging) and contrast agent injection as a predictor of tumour
      response, progression-free survival (PFS) and overall survival (OS). PATIENTS AND
      METHODS: Thirty patients with a metastatic renal cell carcinoma (RCC) already
      enrolled in a double-blind randomised study were evaluated. Examinations were
      performed at baseline, and after 3 and 6 weeks on sorafenib or a placebo in
      patients with tumour targets that were accessible to DCE-US. RESULTS: A total of
      85 examinations were performed, 30 at baseline, 28 at 3 weeks and 27 at 6 weeks.
      The combination of a decrease in contrast uptake exceeding 10% and stability or a
      decrease in tumour volume allowed us to discriminate seven good responders and 20
      poor responders at 3 weeks. There was a statistically significant difference in
      PFS (p=10(-4)) and OS (p=10(-4)) between good and poor responders. CONCLUSION:
      DCE-US is a new noninvasive imaging technique which might be an effective tool
      for evaluating antiangiogenic drugs in renal cancer.

PMID- 16965912
TI  - Phytoestrogens and their low dose combinations inhibit mRNA expression and
      activity of aromatase in human granulosa-luteal cells.
AB  - There is evidence that certain phytoestrogens inhibit aromatase, the enzyme that
      converts androgens to oestrogens. Kinetic studies in cell-free preparations show
      that they may inhibit aromatase by competitive binding to the enzyme, but there
      is a paucity of studies investigating longer-term effects of phytoestrogens on
      the expression of steroidogenic enzymes. This study tested the hypothesis that
      phytoestrogens could reduce aromatase activity by down-regulation of its
      expression. Experiments were carried out on primary cultures of human granulosa
      luteal (GL) cells after they had been exposed to phytoestrogens for 48 h.
      Aromatase activity was measured by the ability of cells to convert testosterone
      to estradiol over a 4h period and aromatase mRNA expression (mRNA(arom)) was
      subsequently measured from the same cells using quantitative real-time PCR. The
      compounds investigated were the flavones, apigenin and quercetin, and the
      isoflavones, genistein, biochanin A and daidzein at doses of 10 microM and 100
      nM. Combinations of these compounds at the lower dose were also investigated. All
      compounds tested dose-dependently reduced mean mRNA(arom) compared with controls.
      Apigenin was the most potent inhibitor with significant inhibition of mRNA(arom)
      seen at both 10 microM and 100 nM, whilst other flavonoids (except biochanin A)
      only induced significant inhibition (p<or=0.05) at the higher dose. Low dose (100
      nM) mixtures of the compounds were ineffective except for a combination of the
      three isoflavones that induced a significant inhibition of mRNA(arom). The
      changes in aromatase activity paralleled the mRNA(arom) results and additional
      studies showed that the reduction in aromatase activity was significantly delayed
      in time compared with the reduction in mRNA(arom.) This is the first study to
      compare the action of various phytoestrogens, either singly or in low-dose
      combination, on the expression and activity of aromatase in human cells and it
      suggests that chronic dietary exposure and tissue accumulation of low-dose
      mixtures of phytoestrogens could have important consequences for aromatase
      activity and the production of oestrogens.

PMID- 16965913
TI  - Isoflavone metabolites and their in vitro dual functions: they can act as an
      estrogenic agonist or antagonist depending on the estrogen concentration.
AB  - The major soy isoflavones are daidzin and genistin, the glycoside conjugates of
      daidzein (DZ) and genistein (GTN). After ingestion, they are metabolized into
      diverse compounds in the gut. The marked inter-individual variation has been
      suggested in their metabolism. The clinical effects may be modulated by the
      metabolic ability to produce a more potent metabolite than the precursor. Our
      study was, therefore, designed to analyze and compare in vitro biologic
      activities of their metabolites: DZ, GTN, dihydrogenistein (DGTN),
      dihydrodaidzein (DDZ), tetrahydrodaidzein (TDZ), O-desmethylangolensin (ODMA),
      and equol (EQL). Furthermore, we investigated their modulatory effects in the
      presence of estrogen using several in vitro systems. The intermediate
      metabolites, such as DGTN, DDZ, and TDZ, bind much weakly to both ERs and induce
      less potently in transcriptional activity, gene expression, and mammary cell
      proliferation than their precursors. EQL has the strongest binding affinities and
      estrogenic activities especially for ERbeta among the daidzin metabolites and
      shows the ability to suppress osteoclast formation at high doses. The test
      isoflavonoids act like estrogen antagonists with the premenopausal dose of E2 and
      thus inhibit estrogenic actions by E2, whereas they exert estrogen agonist
      activity with the lower dose of estrogen close to the serum levels of
      postmenopausal women. Our results suggest that phytoestrogens such as isoflavones
      may exert their effects as estrogen antagonists in a high estrogen environment,
      or they may act as estrogen agonists in a low estrogen environment.

PMID- 16965914
TI  - Down-regulation of adrenal neuronal nitric oxide synthase mRNAs and proteins
      after deoxycorticosterone acetate-salt treatment in rats.
AB  - The aim of this study was to evaluate the possible changes of adrenal neuronal
      nitrite oxide synthase (nNOS) messenger RNA (mRNA) and protein of rats after
      deoxycorticosterone acetate (DOCA)-salt treatment. We determined adrenal nNOS
      expression in 12 vehicle-treated and 13 DOCA-salt-treated rats by in situ
      hybridization, immunohistochemistry, and multiplex RT-PCR methods. Adrenal nNOS
      was also detected by Western blot in five vehicle-treated and five DOCA-salt
      treated rats. The results showed that adrenal nNOS mRNA and nNOS
      immunoreactivities were mainly localized in the medulla and some in the regions
      of zona glomerulosa. DOCA-salt treatment inactivated nNOS mRNA and peptide
      expression prominent in the adrenal medulla and slight in the zona glomerulosa.
      The relative quantities of nNOS mRNA in the adrenals of the DOCA-salt-treated
      group was 8.8-fold decreased. At the same time, the relative quantities of
      steroid acute regulatory protein mRNA and phenylethanolamine N-methyltransferase
      mRNA in the adrenals of the DOCA-salt-treated group were significantly decreased.
      Western blots showed that total adrenal nNOS were 3.7-fold down-regulated after
      DOCA-salt treatment. Our results indicated that the down-regulation of adrenal
      nNOS synthesis might be associated with the inactivation of adrenal function in
      face of volume expansion.

PMID- 16965915
TI  - Production of tropane alkaloids by small-scale bubble column bioreactor cultures
      of Scopolia parviflora adventitious roots.
AB  - The mass production of tropane alkaloids from adventitious root cultures of
      Scopolia parviflora, in small-scale bubble column bioreactor (BCB) was attempted.
      Adventitious roots of S. parviflora produced relatively enhanced levels of
      scopolamine and hyoscyamine in bioreactor compared to flask type cultures, and
      rapidly produced root clumps, with continuously increasing biomass throughout the
      culture period. The production of scopolamine and hyoscyamine in the top and
      bottom regions of root clumps were higher than in the core region. The
      adventitious root cultures of S. parviflora in the BCB required a relatively high
      level of aeration. The optimized conditions for the bioreactor culture growth and
      alkaloid production were found to be 3g of inoculum, on a fresh weight basis, a
      15-day culture period and 0.4vvm of airflow. The elicitation by Staphylococus
      aureus increased the specific compound of scopolamine, while the production of
      hyoscyamine was slightly inhibited in BCB cultures.

PMID- 16965916
TI  - Rear-foot, mid-foot and fore-foot motion during the stance phase of gait.
AB  - This paper proposes a new protocol designed to track a large number of foot
      segments during the stance phase of gait with the smallest possible number of
      markers, with particular clinical focus on coronal plane alignment of the rear
      foot, transverse and sagittal plane alignment of the metatarsal bones, and
      changes at the medial longitudinal arch. The shank, calcaneus, mid-foot and
      metatarsus were assumed to be 3D rigid bodies. The longitudinal axis of the
      first, second and fifth metatarsal bones and the proximal phalanx of the hallux
      were also tracked independently. Skin markers were mounted on bony prominences or
      joint lines, avoiding the course of main tendons. Trajectories of the 14 markers
      were collected by an eight-camera motion capture system at 100 Hz on a population
      of 10 young volunteers. Three-dimensional joint rotations and planar angles were
      calculated according to anatomically based reference frames. The marker set was
      well visible throughout the stance phase of gait, even in a camera configuration
      typical of gait analysis of the full body. The time-histories of the joint
      rotations and planar angles were well repeatable among subjects and consistent
      with clinical and biomechanical knowledge. Several dynamic measurements were
      originally taken, such as elevation/drop of the medial longitudinal arch and of
      three metatarsal bones, rear-foot to fore-foot rotation and transverse plane
      deformation of the metatarsus. The information obtained from this protocol,
      consistent with previous clinical knowledge, enhanced our understanding of the
      dynamics of the human foot during stance.

PMID- 16965917
TI  - A review of 59 consecutive patients with lesions of the anterior cranial base
      operated on using the subcranial approach.
AB  - INTRODUCTION: Lesions of the anterior cranial fossa are still a challenge for the
      surgeon. Since Joram Raveh introduced the concept of a subcranial approach in
      1978 it has been used in the treatment of lesions extending into the anterior
      cranial fossa. Our experience with the subcranial approach during the past 8
      years at Turku University Central Hospital is described. PATIENTS: Fifty-nine
      consecutive patients underwent surgery using the subcranial approach for treating
      various benign and malignant neoplasms, for repair of frontobasal-midfacial
      fractures, and for repair of cerebrospinal fluid leaks. METHODS: Patient records
      were retrospectively reviewed, with special focus on surgical technique, early
      outcome, and complications. RESULTS: Nineteen of the patients were operated on
      because of combined fronto-naso-orbital and skull base fractures, 37 were tumour
      cases, and 3 patients required surgical repair for cerebrospinal fluid leakage.
      Significant complications consisted of two cases of meningitis. However, they
      were successfully treated with antibiotics. The most common late complaint was
      olfactory nerve dysfunction (44), other late complications such as diplopia (4),
      enophthalmos (2), scar tissue in the nasal cavity (2), and trigeminal nerve
      dysfunction (2) were also encountered. CONCLUSION: The subcranial approach
      affords exposure to the orbital, sphenoethmoidal, and clivus regions, as well as
      to the nasal and paranasal cavities. On the basis of this review, it is concluded
      that it is a safe and effective approach for treating lesions involving the
      anterior skull base.

PMID- 16965918
TI  - Midfacial translocation, a variation of the approach to the rhinopharynx, clivus
      and upper odontoid process.
AB  - OBJECTIVE: A surgical variation of the technique of facial translocation
      procedure is proposed, which has been called midfacial translocation for approach
      to the entire medial and lateral region of the middle third of the face,
      including the rhinopharynx, sphenoid sinus, pterygomaxillary fossa, odontoid
      process, and clivus. PATIENTS AND METHODS: The medical records of five treated
      patients accordingly were reviewed for an analysis of the surgical technique, the
      disease, the topography of the lesion, and the complications. RESULTS: The
      approach permitted ventral decompression of the bulbomedullary junction with
      resection of the C1 arch and the odontoid process in four patients and resection
      of a chordoma of the clivus located along the midline and extending intradurally
      in the fifth patient. Only one patient presented with dehiscence of the posterior
      half of the soft palate, this being the only complication observed following
      surgery in these patients. Three months postoperatively, no patient presented any
      aesthetic alteration of the face. Functionally, there was only infraorbital
      hypoaesthesia on the side of flap rotation. CONCLUSION: The technique of
      midfacial translocation provides both good surgical approach and access to the
      rhinopharynx, pterygomaxillary fossa, high odontoid process and clivus, with few
      adverse sequelae for the patient.

PMID- 16965919
TI  - Current determinants of 30-day and 3-month mortality in over 2000 aortic valve
      replacements: Impact of routine laboratory parameters.
AB  - OBJECTIVE: Haematological and biochemical measurements are performed routinely
      before surgery to exclude organ malfunction and blood cell and coagulation
      abnormalities. We aimed to test routinely obtained laboratory data as factors
      predicting operative risk. METHODS: Between 1996 and 2003, 2198 patients
      underwent aortic valve replacement (AVR) (908 of them with concomitant CABG) in
      our institute. The mean age of the study population was 69+/-11 years (range 13
      91, 43% female). Clinical and laboratory parameters based on the consolidated
      data mart set were evaluated by multiple logistic regression analysis. RESULTS:
      The overall operative mortality (within 30 days) was 3.8% and the mortality after
      3 months was 5.9%. In addition to clinical characteristics, the following
      laboratory values were identified as independent predictors of 30-day mortality:
      fasting blood glucose, antithrombine III, partial thromboplastine time and
      creatinine kinase. As independent predictors of 3-month mortality, the following
      laboratory values were indentified: fasting blood glucose, serum creatinine,
      antithrombine III, partial thromboplastine time, lactate dehydrogenase, sodium
      concentration and serum proteins. The discriminative power of the models
      increased if laboratory parameters were included in addition to preoperative
      clinical characteristics (from 0.75 to 0.79 and from 0.75 to 0.78 for 30-day and
      3-month mortality, respectively). The discriminative power using the logistic
      EuroScore was lower (0.71 and 0.7, for 30-day and 3-month mortality,
      respectively). CONCLUSIONS: Laboratory parameters as objective markers for organ
      function and nutritional status are useful data for the prediction of 30-day and
      3-month mortality after aortic valve replacement. Using modern methods of
      information technology, these valuable data which are stored electronically in
      most hospitals, can be used efficiently for research and quality control.

PMID- 16965920
TI  - The older cancer survivor.
AB  - Cancer is an age-related disease, and has increased in prevalence as the
      population has grown older. Improvements in screening and the availability of
      better therapeutic options contribute to burgeoning numbers of cancer survivors,
      who number more than 24 million worldwide. Sixty-one percent of these survivors
      are at least 65 years old. This review is an attempt to consolidate some of the
      data available in the area of cancer survivorship, with emphasis on the elderly.
      Our aim is to provide a better description of the population, elucidate specific
      physical and psychosocial sequelae secondary to cancer and it's treatment, and
      better understand how comorbid conditions, functional status, body-weight, and
      other issues contribute to quality of life, and overall health. This paper also
      suggests some surveillance guidelines for following elderly cancer survivors and
      identifies areas that require further research.

PMID- 16965921
TI  - Kinetic and molecular evidences that human cardiac muscle express non-M2
      muscarinic receptor subtypes that are able to interact themselves.
AB  - In heart tissue five isoforms of the muscarinic acetylcholine receptor (mAChR)
      have been identified, designated m1-m5, of which only M1, M2 and M3 have
      functional evidences for their role in cardiac physiology. The present study was
      designed to explore the diversity of mAChR subtypes in human hearts and determine
      whether these subtypes are able to interact themselves. Expression of mRNAs
      encoding all five subtypes was readily detected by RT-PCR reaction in both atrial
      (A) and ventricle (V) samples. Immunoblotting, MABA and ELISA with subtype
      specific antibodies confirmed the presence of M1, M2, M3, M4 and M5 proteins in
      membrane preparations from both A and V. Kinetic characterization using [(3)H]
      QNB shown: (1) atrium had greater B(max) than did the ventricle, (2) [(3)H]-QNB
      behave as an allosteric modulator, inducing cooperativity at high and disclosing
      heterogeneity at low concentrations, (3) heterogenity was observed in
      pirenzepine, biperiden and tropicamide competition curves, being the high
      affinity sites compatible with M1 and M4 muscarinic receptor subtypes and (4)
      methoctramine competition curves in presence of selective muscarinic receptor
      subtypes antagonist displayed heterogeneity profile still maintaining
      cooperativity (n(H)>1), indicating muscarinic receptors subtypes are able to form
      homo- and hetero-oligomers. In conclusion, our results provide molecular and
      kinetic evidence for the presence of multiple subtypes of mAChR in human hearts,
      which are able to undergo discrete transitions from a non-cooperative kinetics of
      non-interacting monomers to a cooperative kinetics of interacting oligomers.

PMID- 16965922
TI  - The imprint of action: motor cortex involvement in visual perception of
      handwritten letters.
AB  - Humans are able to recognize handwritten texts accurately despite the extreme
      variability of scripts from one writer to another. This skill has been suggested
      to rely on the observer's own knowledge about implicit motor rules involved in
      writing. To investigate the possible neural correlates of such an ability, we
      monitored with magnetoencephalography (MEG) the approximately 20-Hz oscillations
      originating from the motor cortex. The oscillations were more suppressed after
      visual presentation of handwritten than printed letters, indicating stronger
      excitation of the motor cortex to handwritten scripts. These results support the
      idea of embodied visual perception of handwritten scripts and the involvement of
      the motor cortex in the underlying action-perception link.

PMID- 16965923
TI  - Degradable hydrogel scaffolds for in vivo delivery of single and dual growth
      factors in cartilage repair.
AB  - OBJECTIVE: As our population ages, treatment for joint pain associated with
      articular cartilage damage is becoming a prevalent challenge. Accordingly, this
      work investigates local delivery of two regulatory proteins - transforming growth
      factor-beta1 (TGF-beta1) and insulin-like growth factor-1 (IGF-1) - to cartilage
      defects from degradable scaffolds as a potential strategy for improving cartilage
      repair. METHOD: The effects of TGF-beta1 and/or IGF-1 delivery on osteochondral
      repair in adult rabbits were examined through histomorphometric analysis of 11
      markers of osteochondral repair. RESULTS: Complete scaffold degradation occurred
      allowing for assessment of the healing response at 12 weeks post-surgery. When
      compared to untreated defects, higher scores were observed with IGF-1-treated
      defects for the six markers of neo-surface repair: neo-surface morphology,
      cartilage thickness, surface regularity, chondrocyte clustering, and the
      chondrocyte/glycosaminoglycan content of the neo-surface and the cartilage
      surrounding the defect. Surprisingly, the benefits of IGF-1 delivery were not
      maintained when this growth factor (GF) was co-delivered with TGF-beta1, despite
      numerous in vitro reports of the combinatory actions of these GFs. CONCLUSIONS:
      While localized delivery of IGF-1 may be a promising repair strategy, further in
      vivo assessment is necessary, since fibrous tissue was commonly observed in the
      neo-surface of all treatment groups. More importantly, this study highlights the
      need to rigorously examine GF interactions in the wound healing environment and
      demonstrates that in vitro observations do not directly translate to the in vivo
      setting.

PMID- 16965924
TI  - Bacteroides thetaiotaomicron in posthysterectomy infection.
AB  - We report a patient with clinically significant vaginal posthysterectomy
      infection due to Bacteroides thetaiotaomicron. The microorganism isolated from
      the vaginal cuff abscess was beta-lactamase producer and the antibiotic
      susceptibility pattern showed its resistance to piperacillin-tazobactam and
      cefoxitin, while the susceptibility to amoxicillin associated with clavulanic
      acid, metronidazole, and the newer fluoroquinolone moxifloxacin was confirmed.

PMID- 16965925
TI  - Isolation of Dialister pneumosintes isolated from a bacteremia of vaginal origin.
AB  - In this report, we review one case of bacteremia infection due to Dialister
      pneumosintes. The patient was admitted in post-partum with vaginosis and
      suppurative thrombosis of the ovarian veina. D. pneumosintes was isolated in pure
      culture from the three blood culture flasks. Identification of this bacterium was
      difficult and requires the amplification and partial sequencing of the 16S rRNA
      gene. The patients had favorable outcome after antibiotic treatment.

PMID- 16965926
TI  - [Blood transfusion and advertising].
AB  - The Red-Cross and Red-Crescent International Museum has been owning from 1995 a
      collection (series) of 12,000 posters coming from the International Federation of
      the Red-Cross and Red-Crescent National Societies. These posters are dedicated to
      the prevention of diseases and health promotion. Blood donation is featured
      everywhere in this package. While the interpretation of the whole set is
      underway, this article presents some of these topics based on the display of some
      ten posters.

PMID- 16965927
TI  - Ultrasound pasteurization: the effects of temperature, soluble solids, organic
      acids and pH on the inactivation of Escherichia coli ATCC 25922.
AB  - The objectives of this research were to study the effects of temperature, sugar
      concentration (8, 12, and 16 g/100ml), organic acids (citric and malic acids) and
      pH (2.5 and 4.0) on ultrasound pasteurization. The model organism used for the
      research was Escherichia coli ATCC 25922, and ultrasound treatment times were
      conducted to achieve a 5 log (base 10) reduction. Ultrasound generates heat,
      therefore the study involved removing the heat using a jacketed beaker with
      refrigerant (-30 degrees C) to maintain processing temperature at or below 30
      degrees C and eliminate the thermal inactivation effects. Overall, ultrasound
      increased the sensitivity of E. coli to thermal inactivation. The presence of
      soluble solids had a protective effect where the sonication time requirement
      increased. Similar to heat sensitivity, the lower pH environment resulted in E.
      coli having less resistance to sonication. The type of organic acid had the least
      significant effect on ultrasound inactivation of E. coli.

PMID- 16965928
TI  - Shaving diffusion tensor images in discriminant analysis: a study into
      schizophrenia.
AB  - A technique called 'shaving' is introduced to automatically extract the
      combination of relevant image regions in a comparative study. No hypothesis is
      needed, as in conventional pre-defined or expert selected region of interest
      (ROI)-analysis. In contrast to traditional voxel based analysis (VBA),
      correlations within the data can be modeled using principal component analysis
      (PCA) and linear discriminant analysis (LDA). A study into schizophrenia using
      diffusion tensor imaging (DTI) serves as an application. Conventional VBA found a
      decreased fractional anisotropy (FA) in a part of the genu of the corpus callosum
      and an increased FA in larger parts of white matter. The proposed method
      reproduced the decrease in FA in the corpus callosum and found an increase in the
      posterior limb of the internal capsule and uncinate fasciculus. A correlation
      between the decrease in the corpus callosum and the increase in the uncinate
      fasciculus was demonstrated.

PMID- 16965929
TI  - Binding of dimethyl 2,3-naphthalenedicarboxylate with alpha-, beta- and gamma
      cyclodextrins in aqueous solution.
AB  - Fluorescence has been used to investigate the complexes of 2,3-dimethyl
      naphthalenedicarboxylate with naturally occurring alpha-, beta- and gamma
      cyclodextrins. Emission spectra upon excitation of the naphthoate group show two
      peaks whose ratio of intensities R is the sensitive to the medium polarity. The
      change of R with cyclodextrin concentration and temperature allows us to obtain
      the stoichiometry, the formation constants and the changes of enthalpy and
      entropy upon inclusion. Complexes show 1:1 stoichiometry. R extrapolated at [CD]-
      >infinity and the analysis of quenching and polarization measurements, as well
      as, molecular mechanics calculations in the presence of water, permit us to
      explain the geometry of the complexes, the possible location of the guest in
      conformity with thermodynamics parameters and the forces responsible for the
      complexation.

PMID- 16965930
TI  - Spectroscopic techniques and cyclic voltammetry with synthesis: manganese(II)
      coordination stability and its ligand field parameters effect on macrocyclic
      ligands.
AB  - Manganese(II) macrocyclic complexes are prepared with different macrocyclic
      ligands, containing cyclic skeleton bearing organic components which have
      different chromospheres like N, O and S donor atoms and stereochemistry. Thus,
      six macrocyclic ligands, were prepared and their capacity to retain the
      manganese(II) ion in solid as well as in aqueous solution was determined and
      characterized by elemental analyses, molar conductance measurements, magnetic
      susceptibility measurements, mass, (1)H NMR, IR, electronic spectral and cyclic
      voltammetric studies. The electronic spectrum of this system showed a dependence
      that may be consistent with the formation of stable complexes and coordination
      behaviour of the ions. ESR spectra of all the complexes are recorded in solid as
      well as solution, which show the oxidation state of the manganese(II). Spin
      Hamiltonian manganese(II), which can be defined as the magnetic field vector (H):
      H = gBeta(e)HS + D[S(2)(z) - 35/12] + E[S(2)(z) - S(2)(y)] + ASI + (1/6)a
      [S(4)(x) + S(4)(y) + S(4)(z) - 707/16] + (1/180)F[(35S(2)(z) - 475)/(2S(2)(z) +
      3255/10)] Significant distortion of the manganese(II) ion in observed geometry is
      evident from the angle subtended by the different membered chelate rings and the
      angles spanned by trans donor atoms octahedral geometry. Cyclic voltammetric
      studies indicate that complexes with all ligands undergoes one electron oxidation
      from manganese(II) to manganese(III) followed by a further oxidation to
      manganese(IV) at a significantly more positive potential.

PMID- 16965931
TI  - Determination of reorganization energy of fluorenone and 4-hydroxyfluorenone in
      neat and binary solvent mixtures.
AB  - Steady-state absorption and fluorescence measurements of fluorenone and 4
      hydroxyfluorenone in neat and binary solvent mixtures were used to explore the
      reorganization energy in liquid system. The results of spectroscopic measurements
      were used to calculate, according to Marcus theory, the outer-sphere solvent
      reorganization energy, lambda(0), and the internal molecular reorganization
      energy, lambda(in). Preferential solvation of fluorenone and 4-hydroxyfluorenone
      in binary solvent mixtures has been studied by monitoring the outer-sphere
      solvent reorganization energy. In cyclohexane-tetrahydrofuran mixtures, the
      deviation from linearity in the lambda(0) versus the solution polarity is due to
      non-specific dipolar solvent-solute interactions. For cyclohexane-ethanol binary
      mixtures, both non-specific and specific (hydrogen bond) interactions contribute
      to the observed changes.

PMID- 16965932
TI  - DFT and ab initio calculations of the vibrational frequencies and visible spectra
      of triazenes derived from cyclic amines.
AB  - We present a detailed analysis of the structural, infrared spectra and visible
      spectra of the 4-substituted aminoazo-benzenesulfonyl azides. The preparation of
      4-sulfonyl azide benzenediazonium chloride with cyclic amines of various ring
      sizes (pyrrolidine, piperidine, 4-methylpiperidine, N-methylpiperazine,
      morpholine and hexamethyleneimine) have been investigated theoretically by
      performing HF and DFT levels of theory using the standard 6-31G* basis set. The
      optimized geometries and calculated vibrational frequencies are evaluated via
      comparison with experimental values. The vibrational spectral data obtained from
      solid phase FT-IR spectra are assigned modes based on the results of the
      theoretical calculations. The observed spectra are found to be in good agreement
      with the calculations.

PMID- 16965933
TI  - A fluorescence ratiometric nano-pH sensor based on dual-fluorophore-doped silica
      nanoparticles.
AB  - We have synthesized dual-fluorophore-doped core-shell silica nanoparticles used
      as ratiometric pH sensor. The nanoparticles were prepared with a reverse
      microemulsion technique by simultaneously encapsulating two different
      fluorophores, the pH-sensitive dye fluorescein as a pH indicator and the pH
      insensitive dye phenosafranine as an internal reference for fluorescence
      ratiometric measurement, into silica shell. The nanoparticles prevent the
      fluorescence dyes leaching from the silica matrix when immersed inside water. The
      hydrophilic silica shells were made by hydrolysing and polymerizing
      tetraethoxysilane (TEOS) in water-in-oil microemulsion. The fluorescence
      intensity ratio of the two dyes varied linearly as a function of pH in the range
      from 4.0 to 8.0. The sensor was also applied to measure pH of real water samples.
      The results are in good agreements with that using the conventional glass
      electrode method. The as-prepared fluorescent nanoparticles showed rapid
      response, excellent stability and high reproducibility as pH sensors.

PMID- 16965934
TI  - Theoretical studies of molecular structure and vibrational spectra of melaminium
      citrate.
AB  - The molecular geometry and vibrational frequencies of melaminium citrate in the
      ground state have been calculated using the Hartree-Fock (HF) and density
      functional method (B3LYP) with 6-31G(d) basis set. The optimized geometric bond
      lengths and bond angles obtained by using HF and density functional theory (DFT,
      B3LYP) show the best agreement with the experimental data. Comparison of the
      observed fundamental vibrational frequencies of melaminium citrate and calculated
      results by density functional B3LYP and Hartree-Fock methods indicate that B3LYP
      is superior to the scaled Hartree-Fock approach for molecular vibrational
      problems.

PMID- 16965935
TI  - Novel fluorogenic probe for fluoride ion based on the fluoride-induced cleavage
      of tert-butyldimethylsilyl ether.
AB  - A highly sensitive and selective fluorogenic probe for fluoride ion, 4
      methylumbelliferyl tert-butyldimethylsilyl ether (4-MUTBS), was designed and
      synthesized. 4-MUTBS was a weakly fluorescent compound and was synthesized via
      the one-step reaction of 4-MU with tert-butyldimethylsilyl chloride. Upon
      incubation with fluoride ion in acetone-water solution (7:3, v/v), the Si-O bond
      of 4-MUTBS was cleaved and highly fluorescent 4-methylumbelliferone (4-MU) was
      released, hence leading to the fluorescence increase of the reaction solution.
      The fluorescence increase is linearly with fluoride concentration in the range 50
      8000 nmol l(-1) with a detection limit of 19 nmol l(-1) (3sigma). Because of the
      high affinity of silicon toward fluoride ion, the proposed probe shows excellent
      selectivity toward fluoride ion over other anions. The method has been
      successfully applied to the fluoride determination in toothpaste and tap water
      samples.

PMID- 16965936
TI  - Bischromophoric styrylpyridinium dyes. Spectroscopic properties of 1,3-bis-[4-(p
      N,N-dialkylaminostyryl)pyridinyl]propane dibromides.
AB  - The photophysical properties of newly synthesized bischromophoric solvatochromic
      stilbazolium dyes, 1,3-bis-[4-(p-N,N-dialkylaminostyryl)pyridinyl]propane
      dibromides (C1-C9), were studied in a series of solvents and their spectroscopic
      properties were compared with structurally related, monochromophoric
      styrylpyridinium dyes (SP1-SP9). The position of the UV-vis absorption spectra
      maximum of novel dyes is only slightly solvent polarity dependent in contrast to
      the fluorescence spectra that show pronounced solvatochromic effect demonstrated
      by a large Stokes shifts. The influence of the solvent on absorption and emission
      spectra, and the solvatochromic properties observed for both ground and first
      excited states for all the dyes were used for the evaluation of their excited
      state dipole moments. The ground state dipole moments of both mono- and
      bischromophoric dyes were established by applying ab initio calculations. The
      calculations and measurements unexpectedly show that the bischromophoric dyes are
      characterized by ground state dipole moments being equal to about half of that
      characterizing their monomeric equivalents, while the excited state dipole
      moments of bischromophoric dyes are about 10-25% higher in comparison to their
      monomeric equivalents.

PMID- 16965937
TI  - Thermal, spectroscopic, and solvent influence studies on mixed-ligand copper(II)
      complexes containing the bulky ligand: Bis[N-(p-tolyl)imino]acenaphthene.
AB  - Four mixed-ligand copper(II) complexes containing the rigid bidentate nitrogen
      ligand bis[N-(p-tolyl)imino]acenaphthene (abb. p-Tol-BIAN) ligand are reported.
      These complexes, namely [Cu(p-Tol-BIAN)(2)](ClO(4))(2)1, [Cu(p-Tol
      BIAN)(acac)](ClO(4)) 2, [Cu(p-Tol-BIAN)Cl(2)] 3 and [Cu(p-Tol
      BIAN)(AcOH)(2)](ClO(4))(2)4 (where acac, acetylacetonate and AcOH, acetic acid)
      have been prepared and characterized by elemental analysis, spectroscopic,
      magnetic and molar conductance measurements. ESR spectra suggest a square planar
      geometry for complexes 1 and 2. In complexes 3 and 4, a distorted tetrahedral
      arrangement around copper(II) centre was suggested. Solvatochromic behavior of
      all studied complexes indicates strong solvatochromism of their solutions. The
      observed solvatochromism is mainly due to the solute-solvent interaction between
      the chelate cation and the solvent molecules. Thermal properties and
      decomposition kinetics of all complexes are investigated. The kinetic parameters
      (E, A, Delta H, Delta S and Delta G) of all thermal decomposition stages have
      been calculated using the Coats-Redfern and other standard equations.

PMID- 16965938
TI  - Management and outcomes of hepatic cirrhosis: Findings from the RING study.
AB  - BACKGROUND/AIM: Hepatic cirrhosis is a frequent reason for ordinary hospital
      admission (OA). The RING study collected hospital discharge files (HDF) from
      Italian hospital gastroenterology units (IGU). This caselist provides a broad
      picture of the patients admitted for this pathology. MATERIAL/METHODS: More than
      50,000 HDF for OA were collected between 2001 and 2004 from 26 IGU. RESULTS:
      Eight thousand four hundred and eighty-seven HDF (16%) had a diagnosis of hepatic
      cirrhosis; Child-Pugh classes were 20.2% A, 34.8% B and 45.0% C. Patients' mean
      age was 63.7+/-12.1 years and 62.5% were male. A 61.1% of the cirrhosis cases had
      ascites, 29.9% portal-systemic encephalopathy, 29.2% hepatocellular carcinoma
      (HCC), 10% bleeding varices, 3.0% hepatorenal syndrome (HRS). Mortality for OA
      for cirrhosis was 5.7% versus 2.6% for other diagnoses. The proportion varied
      with the severity of the cirrhosis: 0% for Child A, 1.1% B, 10.5% C. Mortality
      was significantly associated with: Child-Pugh at admission (odds ratio: OR 9.2),
      HRS (OR 11.7), bleeding varices (OR 2.2), HCC (OR 1.8). CONCLUSIONS: Hepatic
      cirrhosis was found in 16% of the OA to IGU and mortality was double the rate for
      all the other pathologies in the same wards. Child-Pugh is a useful prognostic
      tool, higher classes implying a greater risk of death. HRS and bleeding varices
      were the complications with most influence on in-hospital mortality.

PMID- 16965939
TI  - Combined passive and active immunoprophylaxis for preventing perinatal
      transmission of the hepatitis B virus in infants born to HBsAg positive mothers
      in comparison with vaccine alone.
AB  - BACKGROUND: In order for liver cirrhosis and hepatocellular carcinoma not to be
      inflicted upon in infants' lifetime, it is essential to prevent hepatitis B virus
      (HBV) infection in them. OBJECTIVES: The aim of this study is to reveal the
      efficacy of passive and active immunoprophylaxis in preventing perinatal
      transmission of HBV in Iran. STUDY DESIGN: In this cohort study with historical
      controls, 823 children born to the HBsAg positive mothers were evaluated. Out of
      this number, 638 had received neither hepatitis B (HB) vaccine nor hepatitis B
      immune globulin (HBIG) and aged more than 16 years (n=481, group 1) or 16 years
      or less (n=157, group 2). The other 125 persons had received only HB vaccine
      (group 3), and 60 neonates received both HB vaccine and HBIG (group 4). RESULTS:
      The prevalence of HBsAg in groups 1, 2, 3 and 4 was 56.1%, 40.3%, 12.6%, and
      3.6%, respectively. The prevalence of anti-HBsAb had a significantly descending
      rate in groups 4 (85.7%), 3 (68.8%), 2 (33.3%), and 1 (21.8%), respectively.
      CONCLUSIONS: The addition of HBIG to recombinant vaccine will significantly
      increase the protection against HBV infection in comparison with HB vaccine
      alone.

PMID- 16965940
TI  - Mesenchymal stem cells overexpressing Akt dramatically repair infarcted
      myocardium and improve cardiac function despite infrequent cellular fusion or
      differentiation.
AB  - We previously reported that intramyocardial injection of bone marrow-derived
      mesenchymal stem cells overexpressing Akt (MSC-Akt) efficiently repaired
      infarcted rat myocardium and improved cardiac function. Controversy still exists
      over the mechanisms by which MSC contribute to tissue repair. Herein, we tested
      if cellular fusion of MSC plays a determinant role in cardiac repair. We injected
      MSC expressing Cre recombinase, with or without Akt, into Cre reporter mice. In
      these mice, LacZ is expressed only after Cre-mediated excision of a loxP-flanked
      stop signal and is indicative of fusion. MSC engraftment within infarcted
      myocardium was transient but significantly enhanced by Akt. MSC fusion with
      cardiomyocytes was observed as early as 3 days, but was infrequent, and we found
      a low rate of differentiation of MSC into cardiomyocytes. MSC-Akt decreased
      infarct size at 3 days and restored early cardiac function. In conclusion, MSC
      Akt improved early repair despite transient engraftment, low levels of cellular
      fusion, and differentiation. These new observations further confirm our recently
      reported data that early paracrine mechanisms mediated by MSC are responsible for
      enhancing the survival of existing myocytes and that Akt could alter the
      secretion of various cytokines and growth factors.

PMID- 16965941
TI  - Endosialin is expressed on stromal fibroblasts and CNS pericytes in mouse embryos
      and is downregulated during development.
AB  - Endosialin has been assigned the alternate name of tumour endothelial marker 1
      (TEM1) due to its identification as a highly upregulated gene transcript in
      tumour endothelium compared to normal endothelium. As a consequence there is
      interest in endosialin as a potential therapeutic target in cancer treatment.
      However, there are conflicting reports over the nature of vascular expression in
      tumours with some evidence that endosialin is expressed on perivascular pericytes
      rather than the endothelial cells themselves. To address this, we have analysed
      the expression of endosialin in mouse embryos, newborn pups and adults. In the
      embryo endosialin is predominantly expressed on stromal fibroblasts throughout
      the mesenchyme but expression is also observed on the developing vasculature.
      When analysed by confocal microscopy endosialin on vessels does not colocalise
      with endothelial cells expressing CD31. Rather, endosialin is restricted to
      closely associated perivascular cells that also express the pericyte marker NG2.
      Finally, the fibroblast and pericyte expression of endosialin changes dynamically
      during development and becomes highly restricted in adult mouse tissues. This
      evolving picture of endosialin expression in sites of active tissue remodelling
      and neovascularisation has implications in tumour growth, angiogenesis and
      metastasis.

PMID- 16965942
TI  - Epigenetics, disease, and therapeutic interventions.
AB  - Heritable changes in gene expression that do not involve coding sequence
      modifications are referred to as "epigenetic". Epigenetic mechanisms principally
      include DNA methylation and a variety of histone modifications, of which the best
      characterized is acetylation. DNA hypermethylation and histone hypoacetylation
      are hallmarks of gene silencing, while DNA hypomethylation and acetylated
      histones promote active transcription. Aberrant DNA methylation and histone
      acetylation have been linked to a number of age related disorders including
      cancer, autoimmune disorders and others. Since epigenetic alterations are
      reversible, modifying epigenetic marks contributing to disease development may
      provide an approach to designing new therapies. Herein we review the role of
      epigenetic changes in disease development, and recent advances in the therapeutic
      modification of epigenetic marks.

PMID- 16965943
TI  - Evaluation of radial chromatography versus axial chromatography, practical
      approach.
AB  - Developments in packing and packing port design of radial columns in recent years
      have resulted in a claimed significant increase in performance of this process
      chromatography technology. In this first study, the main chromatographic
      parameters as efficiency, capacity factor, asymmetry and resolution were
      evaluated in a unique one-to-one comparison between a 120 ml bed-volume and 6 cm
      bed length radial chromatography mini-process column against a 50 mm diameter, 6
      cm bed height and 120 ml bed-volume axial chromatography column. Radial
      chromatography showed an increase in efficiency by 31% in the number of plates
      per meter while the equilibration could be reduced by 0.4-0.5 column volumes. The
      asymmetry factor for bovine serum albumin in radial chromatography showed a
      reduction of 20% while the reduction of the asymmetry factor of the smaller
      protein ovotransferrin decreased even by 46% in comparison to the performance of
      the comparative axial chromatography column. Therefore in radial chromatography
      resolution improved up to 20%. The retention volume was similar in both cases.
      For radial chromatography, the decrease in "width at half height" at Height
      Equivalent of Theoretical Plates (HETP) measurements was 40% while the decrease
      of the over-all width of the peak was 27%. For adsorbed/desorbed proteins, the
      elution peak showed similar results: "width at half height" decreased to 45%
      while the over-all width of the peak decreased by 28%. The concentration of the
      non-retained protein in the flow-through (lysozyme), increased by 35% while the
      concentration of the eluted fraction (serum albumin bovine), increased with 40%
      in the radial chromatography columns. The better results obtained with the radial
      column were probably the consequence of the geometrical design of this device
      (larger inlet surface area and small outlet surface area which concentrate the
      eluted fraction).

PMID- 16965944
TI  - Analysis of the sulphur mustard metabolites thiodiglycol and thiodiglycol
      sulphoxide in urine using isotope-dilution gas chromatography-ion trap tandem
      mass spectrometry.
AB  - A sensitive method has been developed for the trace analysis of the sulphur
      mustard metabolite thiodiglycol (TDG) in urine, and its oxidation product
      thiodiglycol sulphoxide (TDGO) after reduction to thiodiglycol. Thiodiglycol was
      extracted from urine by solid phase extraction onto a polymeric cartridge and,
      after isolation, converted to its bis-heptafluorobutyryl derivative with
      heptafluorobutyryl imidazole. An ion trap mass spectrometer in selected reaction
      monitoring mode detected spiked concentrations down to 0.2 ng/ml with a signal to
      noise ratio>3:1. Urine, from human volunteers with no known exposure to sulphur
      mustard, contained detectable but very low concentrations (<0.2 ng/ml) of
      thiodiglycol, consistent with previous observations using different
      methodologies. Combined concentrations of thiodiglycol and thiodiglycol
      sulphoxide were determined after reduction of the latter with titanium
      trichloride. In this case higher background levels (up to 3 ng/ml) were observed,
      consistent with the sulphoxide being the major excretion product of the two
      metabolites. The method was applied to urine samples, stored frozen for 13 years,
      from two casualties of accidental mustard poisoning. Levels of thiodiglycol were
      1 and 3 ng/ml, which increased to 78 and 104 ng/ml after treatment of the urine
      with titanium trichloride.

PMID- 16965945
TI  - Capsule endoscopy: an alternative to duodenal biopsy for the recognition of
      villous atrophy in coeliac disease?
AB  - BACKGROUND: Villous atrophy present on a duodenal biopsy remains the 'gold
      standard' diagnostic test for coeliac disease. However, endoscopic biopsy may
      cause morbidity and discomfort. Our aim was to evaluate wireless capsule
      endoscopy as an alternative test for the recognition of villous atrophy. METHOD:
      Twenty-one patients with a positive endomysial antibody referred for endoscopy
      and duodenal biopsy were also offered a wireless capsule endoscopy to evaluate
      their small bowel. Concurrently, other patients (n=23) referred for a wireless
      capsule endoscopy acted as controls. Wireless capsule endoscopy reports were
      assessed for the presence of villous atrophy by one blinded investigator.
      RESULTS: Twenty endomysial antibody positive patients subsequently had villous
      atrophy on duodenal biopsy. The controls all had normal duodenal biopsies (with a
      negative endomysial antibody) and no evidence of villous atrophy noted on their
      wireless capsule endoscopy. Of the 20 endomysial antibody positive patients with
      confirmed villous atrophy on biopsy, 17 had villous atrophy also detected by
      wireless capsule endoscopy. The sensitivity, specificity, positive and negative
      predictive values for wireless capsule endoscopy recognising villous atrophy were
      85%, 100%, 100%, 88.9%, respectively. CONCLUSION: Wireless capsule endoscopy may
      be an option to recognise villous atrophy in patients with a positive endomysial
      antibody who are unwilling, or unable to have a gastroscopy. However, a negative
      test should be followed by a biopsy if coeliac disease is to be excluded.

PMID- 16965946
TI  - Women's responses to two models of antepartum high-risk care: day stay and
      hospital stay.
AB  - AIM: To replicate and extend previous research by examining women's responses to
      two current models of high-risk antenatal care that replaced the traditional bed
      rest model. PARTICIPANTS: A sample of 61 women assigned to high-risk antenatal
      care: 29 in the Antenatal Hospital Unit (ANHU) and 32 in the Pregnancy Day Stay
      Unit (PDSU). METHODS: A longitudinal study with data collected by a range of
      validated tools were used to assess mood, family functioning, stress and physical
      symptoms every 2 weeks from admission into antenatal high-risk care to birthing
      and at 3- and 6-weeks postpartum. Data were analysed for similarities and
      differences and change over time between the two groups of women. FINDINGS:
      Stress from emotions was the highest antenatal stressor for both groups and
      highest for those in hospital. Stress about health increased over time for those
      in the PDSU and varied for those in ANHU. Anxiety was significantly different
      between the groups over time (p<0.01), being highest for the ANHU group and
      decreasing from admission to 6-weeks postnatal for both groups. Sensation Seeking
      (sensory deprivation) showed significant differences (p<0.05) with the highest
      scores in the ANHU group and increasing over time for both groups. Family
      relationships were most disrupted for those in ANHU. Both groups were satisfied
      with support from spouse, family and friends and those in ANHU acknowledged the
      support received from midwifery staff. CONCLUSIONS AND IMPLICATIONS: The
      responses of both the woman and her family differ between the two models of care
      and vary with time. Midwives can use the patterns of response identified of these
      findings to address needs for assistance with family relationships, sensory
      stimulation, information and support and management of anxiety when care is
      required for complications of pregnancy.

PMID- 16965947
TI  - Detrimental effect of oral contraceptives on parameters of bone mass and geometry
      in a cohort of 248 young women.
AB  - The aim of this cross-sectional analysis was to examine the skeletal effects of
      low-dose monophasic oral contraceptive (OC) use in a cohort of 248 young
      Caucasian women aged 18-24 years. Areal bone mineral density (BMD) of the femoral
      neck and lumbar spine was evaluated by dual-energy X-ray absorptiometry.
      Volumetric BMD, bone mineral content (BMC), and bone geometry were assessed in
      the tibia by peripheral quantitative computed tomography (pQCT). The women were
      allocated into ever or never OC users, and also into 5 different OC groups
      according to duration and time of initiation of OC use. Women with >2 years of OC
      use and OC initiation within 3 years after menarche were characterized by 10%
      lower femoral neck areal BMD (P<0.001), 5% lower spine areal BMD (not
      significant, P=0.101), 7% lower distal tibial total BMC (P<0.05), and 6% lower
      total BMC at the tibial shaft (P<0.05) relative to never users. In addition,
      women who had ever used OCs had lower bone mass at the femoral neck and tibial
      shaft, despite similar age, height, weight, BMI, hours of exercise, and calcium
      intake compared with never users. At the tibial shaft, OC users showed reduced
      total cross-sectional area, and increased cortical BMD. In conclusion, our data
      suggest that OC use is associated with a detrimental effect on bone mass in young
      women, and provide further insight into the pathophysiological mechanisms
      involved.

PMID- 16965948
TI  - Comparative genome hybridization reveals specific genomic imbalances during the
      genesis from benign through borderline to malignant ovarian tumors.
AB  - Ovarian cancer is one of the most common types of malignancy in women throughout
      the developed world. Despite recent therapeutic advances, long-term survival is
      poor because ovarian cancer is largely asymptomatic in its early stages.
      Comparative genomic hybridization (CGH) was applied to a series of 8 benign, 8
      borderline, and 17 malignant ovarian to establish genomic imbalances associated
      with tumor progression. Benign and borderline tumors were characterized by losses
      at 1p32 approximately p11, 2q14 approximately q34, 4q13 approximately q34, 5q11
      approximately q23, and 6q12 approximately q24, as well as gains of 6p and
      chromosome 12. Similar chromosomal changes were also detected in malignant tumors
      but included additional chromosomal changes: gains at 1q21 approximately q31, 2p,
      3q, 5p, 7, 10p, 12p, 16p, 17, 19q, 20q, and 22q, as well as losses at X, 3p, 8p,
      9, 11p, 13, 14, and 18. Some individual cases of benign and borderline tumors
      revealed no genetic alterations detectable by CGH, suggesting that these tumors
      may represent a subset of tumors that originate by an alternative mechanism of
      tumorigenesis. Furthermore, our findings reveal that borderline tumors are more
      similar to benign tumors than to malignant tumors with respect to their genetic
      profiles.

PMID- 16965949
TI  - Cytogenetic and molecular genetic changes in malignant mesothelioma.
AB  - Malignant mesothelioma (MM) results from the accumulation of a number of acquired
      genetic events, especially deletions, which lead to the inactivation of multiple
      onco-suppressor genes in a multistep cascade mechanism. Past asbestos exposure
      represents the major risk factor for MM, and the link between asbestos fibers and
      MM has been largely proved by several epidemiologic and experimental studies.
      Asbestos fibers induce DNA and chromosomal damage. Most MM cases have shown
      multiple chromosomal abnormalities. Chromosomal losses are more common than
      gains. The most common cytogenetic abnormality in MM is a deletion in 9p21, the
      locus of CDKN2A, a tumor suppressor gene (TSG). The deletion of CDKN2A is a
      negative prognostic factor in MM. Loss of TSG CDKN2A/p14(ARF) is also common in
      MM and mutations in NF2 occur in approximately half of the cases. Despite the ban
      on asbestos use in Western countries, the incidence of MM is increasing, and
      asbestos is still used in developing countries. This epidemiologic situation
      calls for further research. Ongoing studies are already applying high-throughput
      genomic profiling methods in MM. Genetic alterations observed in MM may be useful
      in differential diagnosis between lung cancer and MM, as diagnostic markers or
      therapeutic targets, and as indicators of premalignancy for primary prevention
      and health surveillance.

PMID- 16965950
TI  - Philadelphia-negative clonal hematopoiesis following imatinib therapy in patients
      with chronic myeloid leukemia: a report of nine cases and analysis of predictive
      factors.
AB  - There are increasing reports of Philadelphia-negative (Ph-negative) clonal
      hematopoiesis developing among patients with chronic myeloid leukemia (CML)
      treated with imatinib mesylate (IM). To establish the incidence and significance
      of these chromosomal abnormalities, we analyzed data on 141 consecutive patients
      with CML treated with IM at the British Columbia Cancer Agency and Vancouver
      General Hospital from 1999 to 2004. The cumulative incidence of developing a Ph
      negative clone three years from the start of IM was 8.7% at a median of 13.3
      months. The Ph-negative clonal abnormalities included monosomy 7 and/or trisomy 8
      (seven patients), monosomy for chromosomes X and 22 (one patient), and a (12;16)
      translocation (one patient). Two of the patients presented with the same
      chromosomal abnormality in both Ph-negative and Ph-positive cells. None of the Ph
      negative clonal abnormalities was associated with myelodysplasia. In a
      multivariate analysis, an interval from diagnosis to initiation of IM of 1 year
      or less was associated with an increased risk of developing a Ph-negative clone
      (relative risk = 20.2; P = 0.025). There was no difference, however, in event
      free survival between patients who did and did not develop Ph-negative clones.
      Therefore, while the development of Ph-negative clonal hematopoiesis in patients
      with CML treated with IM is uncommon, it appears to be more frequent than that
      previously seen with IFN, but it does not seem to confer a worse prognosis.

PMID- 16965952
TI  - Correlation of comparative genomic hybridization results of 100 archival uveal
      melanomas with patient survival.
AB  - Comparative genomic hybridization (CGH) was used to elucidate DNA sequence copy
      number imbalances in 100 archival formalin-fixed, paraffin-embedded (FFPE) uveal
      melanoma cases. Of these 100 cases, 51 were from patients who survived >or=9
      years post diagnosis without evidence of metastasis; the remaining 49 patients
      died from metastatic disease. Viable probe was generated from 82 of the 100
      cases, allowing correlation of CGH findings with survival for all but 18 cases.
      Copy number imbalances revealed by CGH were tested for univariate prognostic
      significance. The most powerful predictor of a poor prognosis was gain of
      18q11.2, which was subsequently compared with other significant chromosomal
      regions, as well as histologic and clinical factors, in a multivariate analysis.
      There was also evidence of differential X chromosome involvement in the survival
      correlations between male and female cases, which may be of significance to
      prognosis. This large-scale CGH analysis of archival material is intended to
      direct further gene-specific study of malignancy in uveal melanoma.

PMID- 16965951
TI  - KCTD11 expression in medulloblastoma is lower than in adult cerebellum and higher
      than in neural stem cells.
AB  - Medulloblastoma (MB) is the most common malignant brain tumor of childhood, and
      the most frequent associated genetic alteration is loss of heterozygosity on
      chromosome region 7p13. Two genes mapping to this region, KCTD11 (alias REN) and
      HIC1, have been proposed as involved in MB pathogenesis. We used real-time
      polymerase chain reaction in 20 tissue samples of primary MB to examine the
      transcriptional level of the two genes, with reference to two types of controls:
      adult cerebellum and fetal neural stem cells. A significant reduction of KCTD11
      expression relative to adult normal cerebellum was detected in 14 of 20 (70%) of
      MB samples. Neural stem cells had even lower levels of KCTD11 expression than did
      MB. HIC1 gene expression was low ( approximately 100 times lower than KCTD11
      expression) in MB, and low also in both adult cerebellum and neural stem cells.
      Hypermethylation of the 5'UTR or the central region of HIC1 (or both) was
      detected in a significant number of MB samples, as well as in cerebellum and
      neural stem cells. Our data suggest that KCTD11 may play an important role in MB
      tumorigenesis, but do not support the role of HIC1 in this tumor development. We
      argue that recognition of the gene or genes important in MB tumorigenesis depends
      in part on defining an appropriate control.

PMID- 16965953
TI  - Metaphase and array comparative genomic hybridization: unique copy number changes
      and gene amplification of medulloblastomas in South America.
AB  - Tumors of the central nervous system are the second most frequent malignancy of
      childhood, accounting for the majority of cancer-related deaths in this age
      group. Among these tumors, medulloblastomas (MB) remain in need of further
      genomic characterization toward understanding of pathogenesis and outcome
      predictors. Eight pediatric embryonal brain tumors were analyzed: five MB (one
      being desmoplastic), one PNET, one medulloepithelioma, and one ependymoblastoma.
      Analyses identified genomic imbalances, including the gain of 16p and the
      nonsyntenic coamplification of MYCN and TERT loci. More detailed FISH analysis
      showed that coamplification of MYCN and TERT in one of the MBs manifested as
      dispersed nuclear speckling, consistent with the presence of double minute
      chromosomes. There was considerable cell-to-cell copy number heterogeneity
      present, but it was clear that both genes were amplified concordantly. The
      amplification of oncogenes seems to play an important role in the pathogenesis of
      MB, and the association between MYCN and TERT amplifications and poor prognosis
      has not been well recognized. The uncharacteristic pattern of genomic imbalances
      detected in MB tumors may be a reflection of the characteristics of these tumors
      occurring in South America.

PMID- 16965954
TI  - PTP-PEST phosphatase variations in human cancer.
AB  - Signal transduction via tyrosine phosphorylation, normally fine-tuned by the
      concerted action of both protein tyrosine kinases and protein tyrosine
      phosphatases (PTPs), is a key mechanism in tumorigenesis. PTP-PEST, a
      ubiquitously expressed cytoplasmic tyrosine phosphatase, is thought to play an
      important role in cell adhesion and motility, and may be involved in metastasis.
      A search for sequence variations within the gene PTPN12 (alias PTP-PEST) was
      performed in breast cancer cell lines, leading to the identification of three
      amino acid substitutions at positions 322, 573, and 709. These alterations were
      also found in squamous cell carcinoma cell lines and could be verified in primary
      human breast and kidney tumor samples. Analysis of peripheral blood samples
      confirmed the germline origin of these alterations. Furthermore, functional
      characterization of the Ile322 and Ala573 PTP-PEST mutants revealed an
      enhancement of in vitro phosphatase activity, whereas the Lys709 variant showed
      reduced catalytic activity. These data demonstrate the existence of PTP-PEST
      variants that might be meaningful for human cancer and underscore the need for
      further characterizing PTP-PEST and its signaling pathways in context of this
      disease.

PMID- 16965955
TI  - Imatinib resistant chronic myelogenous leukemia, BCR-ABL positive by chromosome
      and FISH analyses but negative by PCR, in a child progressing to acute basophilic
      leukemia: cytogenetic follow-up.
AB  - The case of an 11-year-old child with adult-type chronic myeloid leukemia,
      Philadelphia (BCR-ABL) positive, reverse transcription-polymerase chain reaction
      negative for the major, minor, and micro breakpoints is presented. In the course
      of 3 years, the child failed to respond to treatment with hydroxyurea, refused
      all therapy for 6 months, was intolerant to alpha-interferon and progressed,
      while on imatinib, to acute basophilic leukemia. Subsequently he underwent
      successful bone marrow transplantation. A secondary cytogenetic clonal evolution,
      i(17q), developed during hydroxyurea treatment and a tertiary clonal evolution,
      +8, was detected during imatinib treatment. It is not clear to what extent the
      several factors (undefined BCR-ABL breakpoint, treatment avoidance, and initial
      treatment choices, alone or in combination) played a role in the imatinib relapse
      and resistance and in the disease progression. We conclude that close follow-up
      with frequent bone marrow sampling is crucial in order to monitor such patients
      for early relapse and prompt referral for bone marrow transplant.

PMID- 16965956
TI  - A clonal translocation (7;8)(p13;q11.2) in a leiomyoma of the vulva.
AB  - We present the first case of a vulvar leiomyoma studied by cytogenetics. The
      tumor formed a 3.0-cm periurethral nodule in a middle-aged woman and was positive
      for the muscle markers desmin and caldesmon, and for estrogen and progesterone
      receptors. Its karyotype was 46,XX,t(7;8)(p13;q11.2). This translocation has not
      been described in previously reported leiomyomas, regardless of their site of
      origin. The transcription factor PLAG1 gene at 8q12 was not altered by the
      translocation.

PMID- 16965957
TI  - Dicentric (17;20)(p11.2;q11.2): an uncommon cytogenetic abnormality in myeloid
      malignancies.
AB  - We report on two patients with myeloid disorders and complex karyotypes including
      a dicentric chromosome, dic(17;20)(p11.2;q11.2), resulting in the loss of most of
      17p and 20q. The presence of the centromeres of chromosomes 17 and 20 in the
      dic(17;20), as well as the loss of TP53, were confirmed by fluorescence in situ
      hybridization. Deletions of 17p and 20q are recurrent abnormalities in
      hematologic disorders, particularly myelodysplastic syndrome and acute myeloid
      leukemia). However, a dic(17;20) is an uncommon finding. According to the few
      reports in the literature, dic(17;20) is associated with an unfavorable
      prognosis. The key mechanism might be the loss of TP53 as well as other tumor
      suppressor genes in 20q that may have a critical role in tumor genesis.

PMID- 16965958
TI  - High-resolution analysis of 9p loss in human cancer cells using single nucleotide
      polymorphism-based mapping arrays.
AB  - Single nucleotide polymorphism (SNP) mapping arrays were used to perform DNA copy
      number analysis of five human cancer cell lines (four malignant mesotheliomas;
      one non-small cell lung carcinoma) to identify and map the end-points of
      deletions of 9p. All five cell lines exhibited homozygous deletions encompassing
      the CDKN2A (alias INK4A/ARF) and CDKN2B loci. The DNA analysis profiles
      demarcated precisely two different, but overlapping, deletions in each
      mesothelioma cell line, but the lung cancer cells showed two copies of a single
      deletion. In the latter cell line, allele analysis revealed that virtually all
      SNPs for chromosome 9 were homozygous, suggestive of uniparental disomy. These
      findings demonstrate the utility of SNP-based mapping arrays for high-resolution
      analysis of genomic imbalances in cancer cells.

PMID- 16965959
TI  - Deletion (21)(q21.2q22.12) as a sole clonal cytogenetic abnormality in a lobular
      capillary hemangioma of the nasal cavity.
AB  - A clonal deletion (21)(q21.2q22.12) was detected as a sole cytogenetic
      abnormality in a lobular capillary hemangioma (pyogenic granuloma) of the nasal
      cavity. This finding supports a neoplastic, rather than reactive, nature for this
      lesion. To our knowledge, these rare lesions have not previously been studied by
      cytogenetics.

PMID- 16965960
TI  - Karyotypic characteristics of human uterine leiomyoma and myometrial cell lines
      following telomerase induction.
AB  - Uterine leiomyomas are the most frequently diagnosed tumors of the female genital
      tract and the primary cause of hysterectomy in premenopausal women in the United
      States. In vitro model systems for studying these tumors are limited, due to poor
      culture growth. For the present study, myometrial (UtSMC) and uterine leiomyoma
      (UtLM) cell lines and their human telomerase reverse transcriptase (hTERT)
      immortalized counterparts were evaluated by GTL-banding and spectral karyotyping.
      UtSMC, at passage 9 showed the normal female karyotype, 46,XX. UtSMC-hTERT at
      passage 13 (population doubling [PD] 22 post immortalization) had two cell
      clones: 46,XX,der(13)t(10;13)(q11.2;p13)]/46,XX. UtLM, at passage 14, and the
      immortalized counterpart UtLM-hTERT (passage 13, PD 20 post immortalization), had
      the reciprocal translocation t(12;14)(q14;q23) in all cells and monosomy X in a
      fraction of cells. UtLM also displayed genomic instability with 15% of cells
      showing structural abnormalities involving chromosome arms 1p and 5q. UtLM-hTERT
      was karyotypically more stable than the parental line, thereby reflecting the
      inhibition of the accumulation of cytogenetic abnormalities by the maintenance of
      telomere integrity. This phenomenon was not observed in the UtSMC cells.

PMID- 16965961
TI  - TP53 gene R72P polymorphism analysis in patients with Barrett esophagus.

PMID- 16965962
TI  - Rearrangement of the RHOH gene in a case of splenic lymphoma with villous
      lymphocytes.

PMID- 16965963
TI  - A novel isoderivative chromosome 20 in a patient with chronic myelomonocytic
      leukemia.

PMID- 16965964
TI  - Metanephric adenoma mimicking papillary carcinoma arising in a mixed epithelial
      and stromal tumor of the kidney.

PMID- 16965965
TI  - The role of ERCC2 polymorphisms in breast cancer risk.

PMID- 16965966
TI  - The characterisation of the human Wolfram syndrome gene promoter demonstrating
      regulation by Sp1 and Sp3 transcription factors.
AB  - Wolfram Syndrome (DIDMOAD) is an autosomal recessive disorder characterised by
      insulin deficient diabetes mellitus and neurodegeneration. Mutations in a novel
      gene, WFS1, were found in nearly all patients and segregated with the disease.
      The WFS1 gene is expressed in all tissue types studied and the 890aa protein
      product is localised to the endoplasmic reticulum (ER). In this study, we used a
      combination of reporter assays and in vitro and in vivo transcription factor
      binding assays to analyse the regulation of expression of the human WFS1 gene in
      neuronal derived cells. A single transcription start site was mapped and a
      minimal promoter identified within 25 bp upstream of this site. This minimal
      promoter contains two DNA binding motifs (GC boxes) for the transcription factors
      Sp1/3/4 and binding of both Sp1 and Sp3 was demonstrated at both motifs in vitro
      and in vivo. The presence of intact GC boxes is essential for minimal promoter
      action. Thus, transcription factors of the Sp family are important regulators of
      the WFS1 promoter. A further up-regulating control region was identified
      containing three CCAAT box binding motifs; all demonstrated a reduction in
      expression after mutation. One CCAAT box represented part of a predicted ER
      stress response element.

PMID- 16965968
TI  - Superficial soft-tissue lymphoma: sonographic appearance and early survival.
AB  - We evaluated superficial soft-tissue lymphomas on high-resolution ultrasonography
      (HRUS) in 43 patients (17 women, 26 men; mean, 59.7 y; range, 12 to 90 y), with 1
      to 97-month follow-up. Clinical presentations, tumor location and morphology,
      echogenicity on HRUS and color-encoding grades on Doppler ultrasonography (CDUS)
      were assessed. Clinical presentations did not significantly differ with tumor
      location or morphology. Types of lymphoma did not significantly differ in
      echogenicity, although most were hypoechogenic. On CDUS, most lymphomas were
      hypervascular, but grades did not significantly depend on the type of tumor. On
      Kaplan-Meier analysis with log-rank testing, survival did not differ by age
      (divided at 65 y), sex, tumor location or size (cut-off, 5 cm), CDUS grade or
      pathology. Survival was significantly related to clinical presentation (p <
      0.0095) and tumor morphology (p < 0.0354). HRUS and CDUS were good modalities to
      detect the masses and provided important pretreatment information.

PMID- 16965969
TI  - Sonographic features of nonpalpable breast cancer: a study based on ultrasound
      guided wire-localized surgical biopsies.
AB  - The purpose of this study is to investigate the correlation between
      surgicopathological findings and ultrasonic images of nonpalpable breast lesions.
      The study was composed of 220 nonpalpable breast lesions from 193 patients. The
      breast lesions were classified into soft tissue type (185 lesions) and
      calcification type (35 lesions). Of the 220 lesions, 62 (28%) were malignant. For
      soft tissue type lesions, the sonographic features of sound attenuation (p <
      0.001) and irregular border (p < 0.001) were significantly associated with the
      malignant diagnosis. For soft tissue-type and calcification-type lesions, the
      presence of increased vascularity (p < 0.001) or calcification (p < 0.001) was
      significantly associated with the malignant diagnosis. Of the 164 breast lesions
      with corresponding mammograms, 37 of 74 mammographically identifiable lesions
      were pathologically malignant, as compared with 16 of 90 lesions with negative
      mammograms (p < 0.001). In our study, the more sensitive sonographic features for
      predicting malignancy were irregular border and increased vascularity
      (sensitivity 88% and 82%, respectively), whereas the features of sound
      attenuation and presence of calcifications were more specific (specificity 88%
      and 80%, respectively). In conclusion, ultrasound-guided wire localization of
      breast lesions is not only useful in assisting surgical biopsy, but the
      sonographic findings obtained by this procedure correlate with pathologic
      diagnosis.

PMID- 16965970
TI  - Intraoperative brain ultrasound: a new approach to study flow dynamics in
      intracranial aneurysms.
AB  - The aim was to evaluate the potential of contrast-enhanced ultrasound to
      visualize the hemodynamics in intracranial aneurysms during neurosurgical
      intervention and to quantify the ultrasound data using digital particle image
      velocimetry (DPIV) technique. Aneurysms were scanned through the intact dura
      mater, preclipping and again postclipping after closure of the dura. After
      intravenous injection of Optison, angio-like views of the vascular tree
      surrounding the aneurysm, including the aneurysm sac, were obtained. Single
      ultrasound contrast agent microbubbles could be visualized in the aneurysm sac
      and the flow dynamics could be assessed in vivo. Spatial and temporal
      distributions of the velocity in the aneurysm and in the parent vessels were
      measured with DPIV using the backscattered signals from the microbubbles.
      Subsequently, the fluid stresses, vorticity, circulation, etc., were calculated
      from the velocity fields. We demonstrate in this paper that intraoperative
      contrast-enhanced ultrasound can be used to quantify the flow dynamics within an
      aneurysm.

PMID- 16965971
TI  - Skeletal muscle ultrasonography: Visual versus quantitative evaluation.
AB  - In this study, we compared the sensitivity and specificity of visual versus
      quantitative evaluation of skeletal muscle ultrasound in children suspected of
      having a neuromuscular disorder (NMD). Ultrasonography (US) scans of four muscles
      (biceps brachii, forearm flexors, quadriceps femoris, anterior tibial muscle)
      were made in 76 children. All images were visually evaluated using the Heckmatt
      criteria and quantitatively evaluated with computer-assisted grey-scale analysis
      of muscle echo intensity. Visual evaluation could achieve a sensitivity up to
      71%, with a specificity of 92%. With quantification, a sensitivity of 87%
      accompanied by a specificity of 67% was found, but other diagnostic values could
      be achieved, depending on the cut-off point. Quantification resulted in a higher
      interobserver agreement (kappa 0.86) compared with visual evaluation (kappa
      0.53). We conclude that quantification of echo intensity is a more objective and
      accurate method. Because it can achieve higher sensitivities, it is better-suited
      for the screening task in the diagnostic phase of children with a NMD.

PMID- 16965972
TI  - Evaluating the use of a portable ultrasound machine to quantify intima-media
      thickness and flow-mediated dilation: agreement between measurements from two
      ultrasound machines.
AB  - Flow-mediated dilation (FMD) and common carotid intima-media thickness (CIMT) are
      intermediate endpoints for cardiovascular disease. The purpose of this study was
      to determine whether a portable ultrasound machine was capable of valid
      measurements of FMD and CIMT compared with a clinic-based machine under similar
      conditions. Vascular images were taken on 23 apparently healthy young adults with
      the portable type and clinic type instruments. The analyses revealed a high level
      of agreement between the two machines for measurements of mean [corrected] CIMT
      (mean difference [MD] = -0.025 mm, limits of agreement [LOA] = -0.080, 0.029 mm),
      maximum [corrected] CIMT (MD = 0.001 mm, LOA = -0.065, 0.065 mm) and FMD measures
      of brachial diameter (baseline MD = 0.199 mm, LOA = -0.210, 0.608 mm, maximum MD
      = 0.218 mm, LOA = -0.162, 0.597 mm). Reasonable agreement was found for %FMD
      measurements (MD = 0.27%, LOA = -4.91, 5.44%). The within-machine coefficient of
      variation results for mean [corrected] CIMT (5.0%), maximum [corrected] CIMT
      (4.3%), baseline (6.3%) and maximum (5.4%) brachial diameter and %FMD (30.1%)
      were comparable with normal within-subject variation. We conclude that the
      portable ultrasound machine can provide measurements of FMD and CIMT that are
      highly comparable with measurements obtained from a clinic-based machine under
      similar clinical conditions.

PMID- 16965973
TI  - Refill model of rabbit kidney vasculature.
AB  - A refill model previously developed in flow phantoms was modified to simulate the
      refill of cortical and medullary rabbit kidney tissues. The highly structured
      kidney tissues were accounted for by considering refill both within and across
      the scan-plane. Refill curves were acquired with ultrasound contrast from rabbit
      kidneys using high MI disruption pulses followed by low MI real-time imaging. The
      comparison of the real medullary and cortical tissues with their corresponding
      models resulted in an RMS error of 11% and 18%, respectively, indicating that
      simple assumptions about a tissue's vascular structure are predictive of refill
      behaviour. Tissue classification images were generated using the refill models
      and an exponential simplification. These images were indistinguishable and
      matched what is expected of a kidney, indicating that the primary distinguishing
      characteristic between kidney tissue types is mean transit time. However, the
      vascular model is useful in predicting and explaining tissue properties that
      affect refill behavior.

PMID- 16965974
TI  - Needle tip localization using stylet vibration.
AB  - Power Doppler ultrasound is used to localize the tip of a needle by detecting
      physical vibrations. Two types of vibrations are investigated, lateral and axial.
      The lateral vibrations are created by rotating a stylet, whose tip is slightly
      bent, inside a stationary cannula while the stylet is completely within the
      cannula. The minute deflection at the needle tip when rotated causes tissue
      motion. The axial vibration is induced by extending and retracting a straight
      stylet inside a stationary cannula. The stylet's tip makes contact with the
      tissue and causes it to move. The lateral vibration method was found to perform
      approximately the same under a variety of configurations (e.g., different
      insertion angles and depths) and better than the axial vibration method. Tissue
      stiffness affects the performance of the lateral vibration method, but good
      images can be obtained through proper tuning of the ultrasound machine.

PMID- 16965975
TI  - Design and characterisation of a wall motion phantom.
AB  - Arterial wall motion is an essential feature of a healthy cardiovascular system
      and it is known that wall motion is affected by age and disease. In recent years,
      methods have been developed for measurement of wall motion with the intention of
      providing diagnostically useful information. An issue with all of these
      techniques is the accuracy and variability of both wall motion and derived
      quantities such as elasticity, which requires the development of suitable test
      tools. In this paper, a vessel wall phantom is described for use in ultrasound
      studies of wall motion. The vessel was made from polyvinyl alcohol (PVA)
      subjected to a freeze-thaw process to form a cryogel (PVA-C). The elastic
      modulus, acoustic velocity and attenuation coefficient varied from 57 kPa, 1543 m
      s(-1) and 0.18 dB cm(-1) MHz(-1) for one freeze-thaw cycle to 330 kPa, 1583 m s(
      1) and 0.42 dB cm(-1) MHz(-1) for 10 freeze-thaw cycles. Wall motion was effected
      by the use of pulsatile flow produced from a gear pump. The use of a downstream
      flow resistor removed gross distortions in the wall motion waveform, possibly by
      removal of reflected pressure waves. However, a low amplitude 20 Hz oscillation
      remained, which is unphysiologic and thought to be caused by the vibration of the
      distended PVA-C vessel.

PMID- 16965976
TI  - Effect of 3D ultrasound probes on the accuracy of electromagnetic tracking
      systems.
AB  - In the last few years, 3D ultrasound probes have became readily available. New
      fields of image-guided surgery applications are opened by attaching small
      electromagnetic position sensors to 3D ultrasound probes. However, nothing is
      known about the distortions caused by 3D ultrasound probes regarding
      electromagnetic sensors. Several trials were performed to investigate error
      proneness of state-of-the-art electromagnetic tracking systems when used in
      combination with 3D ultrasound probes. It was found that 3D ultrasound probes do
      distort electromagnetic sensors more than 2D probes do. When attaching
      electromagnetic sensors to 3D probes, maximum errors of 5 mm up to 119 mm occur.
      The distortion strongly depends on the electromagnetic technology as well on the
      probe technology used. Thus, for 3D ultrasound-guided applications using
      electromagnetic tracking technology, the interference of ultrasound probes and
      electromagnetic sensors have to be checked carefully.

PMID- 16965977
TI  - The safety of Sonovue in abdominal applications: retrospective analysis of 23188
      investigations.
AB  - The aim of the present retrospective study was to assess the incidence of adverse
      events (AE) of a second-generation ultrasound contrast agent in real clinical
      practice. A total of 28 Italian Centres provided data on the postmarketing use of
      SonoVue (Bracco Spa, Milan, Italy) in abdominal examination performed between
      December 2001 and December 2004. A total of 23 188 investigations were reported.
      No fatal event occurred. AEs were reported in 29 cases, of which only two were
      graded as serious; the rest, 27, were nonserious (23 mild, three moderate and one
      severe). The overall reporting rate of serious AE was 0.0086%. Overall, only four
      AEs required treatment (two serious, two nonserious including one moderate and
      one severe AEs). In conclusion, the present large-scale retrospective analysis
      showed that SonoVue has a good safety profile in abdominal applications, with an
      AE reporting rate lower than or similar to that reported for radiologic and
      magnetic resonance contrast agents.

PMID- 16965978
TI  - Effects of simultaneous application of ultrasound and microbubbles on
      intracerebral hemorrhage in an animal model.
AB  - Microbubble-enhanced sonothrombolysis (MEST) may be an alternative therapeutic
      option in ischemic stroke. Clinical study of the efficacy of MEST as an adjunct
      stroke therapy, before imaging with CT or MRI, requires experimental data on the
      safety of this approach in the presence of hemorrhagic stroke. We, therefore,
      investigated the effect of diagnostic transcranial ultrasound combined with
      microbubbles (US + MB) in an experimental animal model of intracerebral
      hemorrhage (ICH). ICH was induced in anesthetized rats by intracerebral
      collagenase injection. Transcranial ultrasound (2 MHz, mechanical index 1.3, 1051
      kPa) was applied 3 h after ICH induction to rat brains for 30 min during a
      continuous IV infusion of sulfur hexafluoride microbubbles (SonoVue). The size of
      cerebral hemorrhage, the extent of brain edema, and the amount of apoptosis were
      compared with those from control rats with ICH but without US + MB. Results
      showed no significant effect of US + MB on hemorrhage size (control 23.3 +/- 10.7
      mm(3), US + MB 20.3 +/- 5.8 mm(3)), on the extent of brain edema (control 3.3 +/-
      2.0%, US +MB 3.5 +/- 1.9%), or on the rate of apoptosis (control 5.2 +/- 1.5%, US
      + MB 5.2 +/- 1.0%). We conclude that diagnostic ultrasound in combination with
      microbubbles does not cause additional damage to the rat brain during ICH in our
      experimental set-up. This finding provides support for the use of MEST as an
      early stroke therapy.

PMID- 16965979
TI  - Cloud cavitation control for lithotripsy using high intensity focused ultrasound.
AB  - Cloud cavitation is potentially the most destructive form of cavitation. When the
      cloud cavitation is acoustically forced into a collapse, it has the potential to
      concentrate a very high pressure, more than 100 times the acoustic pressure, at
      its center. We experimentally investigate a method to control the collapse of
      high intensity focused ultrasound (HIFU)-induced cloud cavitation to fragment
      kidney stones. Our study examines a novel two-frequency wave designed to control
      the cloud cavitation (cavitation control [C-C] waveform); a high-frequency
      ultrasound pulse (1 to 4 MHz) to create the cloud cavitation and a low-frequency
      trailing pulse (545 kHz) following the high-frequency pulse to force the cloud
      into collapse. High-speed photography has revealed that a localized distribution
      of the cloud cavitation can be produced within 1 mm on the solid surface by the
      high-frequency pulse. The low-frequency ultrasound was irradiated to the high
      frequency-induced cloud cavitation. A subsequent shock wave emitted from the
      cloud cavitation was observed both in the shadowgraph photography and the remote
      hydrophone measurement. Furthermore, in vitro erosion tests of model and natural
      stones were conducted. In the case of model stones, the erosion rate of the C-C
      waveform showed a distinct advantage with the combined high- and low-frequency
      waves over either wave alone. Natural stones were eroded and most of the
      resulting fragments were less than 1 mm in diameter. The results show that the
      control of the cloud cavitation has untapped potential for the lithotripsy
      applications upon further optimization of the ultrasound parameters and
      complementary in vivo studies.

PMID- 16965980
TI  - Brain arterioles show more active vesicular transport of blood-borne tracer
      molecules than capillaries and venules after focused ultrasound-evoked opening of
      the blood-brain barrier.
AB  - Previously, activation of vesicular transport in the brain microvasculature was
      shown to be one of the mechanisms of focused ultrasound-induced blood-brain
      barrier (BBB) opening. In the present study, we aimed to estimate the rate of the
      transendothelial vesicular traffic after focused ultrasound sonication in the
      rabbit brain, using ultrastructural morphometry and horseradish peroxidase (HRP)
      as a tracer. In the capillaries, the mean endothelial pinocytotic densities (the
      number of HRP-containing vesicles per microm(2) of the cell cytoplasm) were 0.9
      and 1.05 vesicles/microm(2) 1 h after sonication with ultrasound frequencies of
      0.69 and 0.26 MHz, respectively. In the arterioles, these densities were 1.63 and
      2.43 vesicles/microm(2), values 1.8 and 2.3 times higher. In control locations,
      the densities were 0.7 and 0.14 vesicles/microm(2) for capillaries and
      arterioles, respectively. A small number of HRP-positive vesicles were observed
      in the venules. Focal delivery of HRP tracer was also observed in light
      microscopy. The results indicate that the precapillary microvessels play an
      important role in macromolecular transcytoplasmic traffic through the ultrasound
      induced BBB modulation, which should be considered in the future development of
      trans-BBB drug delivery strategies.

PMID- 16965981
TI  - Interactions between consecutive sonications for characterizing the thermal
      mechanism in focused ultrasound therapy.
AB  - The use of focused ultrasound for thermal ablation or therapy has become a
      promising modality due to its high selectivity and noninvasiveness. The
      temperature increase that induces thermal necrosis in the focal beam area has
      been reported to be attributed to the absorption of ultrasound energy and heating
      enhancement by acoustic cavitation. The purpose of this study is to propose a
      novel experimental arrangement to observe the thermal lesion formation and to
      demonstrate that the presence of the ultrasound-induced, macroscopically-visible
      bubbles may exert a key effect in thermal lesion formation. In our experiments,
      consecutive sonications with orthogonal intersections were applied to observe the
      thermal lesion interaction induced by 577- or 1155-kHz ultrasound. Results showed
      that the 1155-kHz heating was dominated by ultrasound energy absorption, with
      blocking of consecutive sonications being evident only rarely. However, in 577
      kHz sonications, the thermal process was dominated by inertial cavitation and the
      corresponding ultrasound-induced, macroscopically-visible bubbles, which was
      verified from the later lesion being blocked by the former one and direct
      observation from light microscopy. This study demonstrates that the operating
      frequency for ultrasound thermal ablation should be selected based on the
      intended specific thermal mechanisms to be induced.

PMID- 16965982
TI  - Transfer standard device to improve the traceable calibration of physiotherapy
      ultrasound machines.
AB  - Ultrasound (US) physiotherapy as a clinical treatment is extremely common in the
      Western world. Internationally, regulation to ensure safe application of US
      physiotherapy by regular calibration ranges from nil to mandatory. The need for a
      portable power standard (PPS) has been addressed within a European Community (EC)
      funded project. This PPS consists of an electrical driver, a set of US
      transducers and a cavitation detector (CD). Each component has been extensively
      tested for stability and travel robustness. Transducer output power has been
      determined with an uncertainty of <3.3% and with a long-term (2-y) output
      stability of better than 3%. The CD can detect bubble activity for powers above 3
      W for a 1-MHz transducer. Travel trials demonstrated the utility of the PPS in
      practical measurement environments. Deviations in power measurements observed
      during these trials were mostly acceptable (<10%), although there were also
      examples of gross differences (>100%). The PPS is now ready to be used to
      underpin traceable calibration of physiotherapy devices.

PMID- 16965983
TI  - Low-molecular-weight heparin improves the performance of uterine artery Doppler
      velocimetry to predict preeclampsia and small-for-gestational age infant in women
      with gestational hypertension.
AB  - This study investigated whether a short course of subcutaneous low-molecular
      weight heparin (LMWH) might modify the performance of uterine artery Doppler to
      predict preeclampsia and small-for-gestational age (SGA) newborns in a high-risk
      population. A controlled, open-labeled study included 94 women with gestational
      hypertension and 30 healthy women enrolled at 24 to 26 weeks gestation. Doppler
      evaluation of uterine arteries resistance index (RI) was performed before and
      after a two-week course of LMWH (enoxaparin, 4000 IU/d, n = 56 hypertensive
      patients) or no treatment (n = 38 hypertensive women and 30 healthy controls).
      There was a significant decrease of uterine artery RI after LMWH (p < 0.001,
      paired Student's t-test), whereas the untreated hypertensive patients and the
      healthy control group showed no change between the two Doppler evaluations. The
      change induced by LMWH was restricted to women with normal outcome, whose RI
      decreased from (mean +/- standard error) 0.62 +/- 0.01 to 0.56 +/- 0.01 (p <
      0.0001). By consequence, the second RI measurement, performed after LMWH
      administration, had fewer false positive results and higher positive likelihood
      ratios (LR+) to predict both preeclampsia (LR + 5.91) and SGA (LR + 4.69)
      compared with the first Doppler examination (LR + 1.97 and 2.22, respectively).
      Thus, LMWH improved the performance of uterine artery RI to predict preeclampsia
      and SGA in women with gestational hypertension.

PMID- 16965984
TI  - Just how useful an endpoint is complete pathological response after neoadjuvant
      chemoradiation in rectal cancer?

PMID- 16965985
TI  - National Residency Matching Program results for radiation oncology: 2006 update.

PMID- 16965986
TI  - Image-guided radiotherapy using megavoltage cone-beam computed tomography for
      treatment of paraspinous tumors in the presence of orthopedic hardware.
AB  - PURPOSE: This report describes a new image-guided radiotherapy (IGRT) technique
      using megavoltage cone-beam computed tomography (MV-CBCT) to treat paraspinous
      tumors in the presence of orthopedic hardware. METHODS AND MATERIALS: A patient
      with a resected paraspinous high-grade sarcoma was treated to 59.4 Gy with an
      IMRT plan. Daily MV-CBCT imaging was used to ensure accurate positioning. The
      displacement between MV-CBCT and planning CT images were determined daily and
      applied remotely to the treatment couch. The dose-volume histograms of the
      original and a hypothetical IMRT plan (shifted by the average daily setup errors)
      were compared to estimate the impact on dosimetry. RESULTS: The mean setup
      corrections in the lateral, longitudinal, and vertical directions were 3.6 mm
      (95% CI, 2.6-4.6 mm), 4.1 mm (95% CI, 3.2-5.0 mm), and 1.0 mm (95% CI, 0.6-1.3
      mm), respectively. Without corrected positioning, the dose to 0.1 cc of the
      spinal cord increased by 9.4 Gy, and the doses to 95% of clinical target volumes
      1 and 2 were reduced by 4 Gy and 4.8 Gy, respectively. CONCLUSIONS: Megavoltage
      CBCT provides a new alternative image-guided radiotherapy approach for treatment
      of paraspinous tumors in the presence of orthopedic hardware by providing 3D
      anatomic information in the treatment position, with clear imaging of metallic
      objects and without compromising soft-tissue information.

PMID- 16965988
TI  - The impact of lobular carcinoma in situ in association with invasive breast
      cancer on the rate of local recurrence in patients with early-stage breast cancer
      treated with breast-conserving therapy.
AB  - PURPOSE: The significance of lobular carcinoma in situ (LCIS) associated with
      invasive breast cancer in patients undergoing breast-conserving therapy (BCT)
      remains controversial. We examined the impact of the presence and extent of LCIS
      associated with invasive breast cancer on clinical outcome in BCT patients.
      METHODS AND MATERIALS: From 1980 to 1996, 607 cases of invasive breast cancer
      were treated with BCT. All slides were reviewed by a single pathologist. Positive
      margin was defined as presence of invasive carcinoma/ductal carcinoma in situ at
      the inked margin. Multiple clinical, pathologic, and treatment-related variables
      were analyzed for their association with ipsilateral breast tumor recurrence
      (IBTR) and true recurrence/marginal miss (TR/MM). Median follow-up was 8.7 years.
      RESULTS: Fifty-six patients (9%) had LCIS in association with invasive cancer. On
      univariate analysis, positive final margin, positive/no reexcision, smaller
      maximum specimen dimension, and the presence of LCIS predicted for IBTR. The 10
      year IBTR rate was 14% for cases with LCIS vs. 7% without LCIS (p=0.04). On
      multivariate analysis, positive margin (p<0.01), positive/no reexcision (p=0.04),
      and presence of LCIS (p=0.02) remained independently associated with IBTR;
      positive margin (p<0.01) and LCIS (p=0.04) were also associated with TR/MM
      failure. When examining only cases with negative final margins, the presence of
      LCIS remained associated with higher IBTR and TR/MM rates (p<0.01). CONCLUSION:
      The presence of LCIS was independently associated with higher rate of IBTR and
      TR/MM after BCT for invasive breast cancer. LCIS may have significant
      premalignant potential and progress to an invasive IBTR at the site of index
      lesion. The adequacy of excision of LCIS associated with invasive carcinoma
      should be considered in patients undergoing BCT.

PMID- 16965987
TI  - Epigenetic dysregulation underlies radiation-induced transgenerational genome
      instability in vivo.
AB  - PURPOSE: Although modern cancer radiation therapy has led to increased patient
      survival rates, the risk of radiation treatment-related complications is becoming
      a growing problem. Among various complications, radiation also poses a threat to
      the progeny of exposed parents. It causes transgenerational genome instability
      that is linked to transgenerational carcinogenesis. Although the occurrence of
      transgenerational genome instability, which manifests as elevated delayed and
      nontargeted mutation, has been well documented, the mechanisms by which it arises
      remain obscure. We hypothesized that epigenetic alterations may play a pivotal
      role in the molecular etiology of transgenerational genome instability. METHODS
      AND MATERIALS: We studied the levels of cytosine DNA methylation in somatic
      tissues of unexposed offspring upon maternal, paternal, or combined parental
      exposure. RESULTS: We observed a significant loss of global cytosine DNA
      methylation in the thymus tissue of the offspring upon combined parental
      exposure. The loss of DNA methylation was paralleled by a significant decrease in
      the levels of maintenance (DNMT1) and de novo methyltransferases DNMT3a and 3b
      and methyl-CpG-binding protein MeCP2. Along with profound changes in DNA
      methylation, we noted a significant accumulation of DNA strand breaks in thymus,
      which is a radiation carcinogenesis target organ. CONCLUSIONS: The observed
      changes were indicative of a profound epigenetic dysregulation in the offspring,
      which in turn could lead to genome destabilization and possibly could serve as
      precursor for transgenerational carcinogenesis. Future studies are clearly needed
      to address the cellular and carcinogenic repercussions of those changes.

PMID- 16965989
TI  - Consistency in seroma contouring for partial breast radiotherapy: impact of
      guidelines.
AB  - PURPOSE: Inconsistencies in contouring target structures can undermine the
      precision of conformal radiation therapy (RT) planning and compromise the
      validity of clinical trial results. This study evaluated the impact of guidelines
      on consistency in target volume contouring for partial breast RT planning.
      METHODS AND MATERIALS: Guidelines for target volume definition for partial breast
      radiation therapy (PBRT) planning were developed by members of the steering
      committee for a pilot trial of PBRT using conformal external beam planning. In
      phase 1, delineation of the breast seroma in 5 early-stage breast cancer patients
      was independently performed by a "trained" cohort of four radiation oncologists
      who were provided with these guidelines and an "untrained" cohort of four
      radiation oncologists who contoured without guidelines. Using automated planning
      software, the seroma target volume (STV) was expanded into a clinical target
      volume (CTV) and planning target volume (PTV) for each oncologist. Means and
      standard deviations were calculated, and two-tailed t tests were used to assess
      differences between the "trained" and "untrained" cohorts. In phase 2, all eight
      radiation oncologists were provided with the same contouring guidelines, and were
      asked to delineate the seroma in five new cases. Data were again analyzed to
      evaluate consistency between the two cohorts. RESULTS: The "untrained" cohort
      contoured larger seroma volumes and had larger CTVs and PTVs compared with the
      "trained" cohort in three of five cases. When seroma contouring was performed
      after review of contouring guidelines, the differences in the STVs, CTVs, and
      PTVs were no longer statistically significant. CONCLUSION: Guidelines can improve
      consistency among radiation oncologists performing target volume delineation for
      PBRT planning.

PMID- 16965990
TI  - Evaluation of postradiotherapy PSA patterns and correlation with 10-year disease
      free survival outcomes for prostate cancer.
AB  - PURPOSE: To describe the prostate-specific antigen (PSA) pattern profiles
      observed after external beam radiotherapy with and without short-term neoadjuvant
      androgen deprivation therapy (ST-ADT) and to report the association of
      established posttreatment PSA patterns with long-term disease-free survival
      outcomes. METHODS AND MATERIALS: A total of 1,665 patients were treated with
      conformal external beam radiotherapy for clinically localized prostate cancer. Of
      570 patients who had the requisite>10 consecutive PSA measurements for
      statistical analysis, 194 patients received a median of 3 months of ADT before
      radiotherapy and 376 were treated with radiotherapy alone. The median follow up
      was 103 months. RESULTS: In the group treated with ST-ADT, three distinct
      postradiotherapy PSA patterns were identified: a stable trend (44%), an
      increasing trend followed by stabilization of the PSA (25%), and an increasing
      trend (31%). Among the subgroup that demonstrated a rising and subsequent
      stabilizing patterns, PSA levels had gradually risen to a median value of 0.9
      ng/mL after therapy, stabilized, and remained durably suppressed. The only
      identified trends among patients treated with external beam radiotherapy without
      ST-ADT were declining PSA levels followed by stable PSA trends or declining
      patterns followed by rising levels. Patients whose PSA levels stabilized after an
      initial rise or those with slowly rising PSA profiles had a lower incidence of
      distant metastasis compared to those with accelerated rises after therapy.
      CONCLUSIONS: For those treated with external beam radiotherapy in conjunction
      with ST-ADT, a significant percentage who develop a rising PSA after treatment
      are expected to manifest subsequent stabilization at plateaued levels of
      approximately 1.0 ng/mL, which can remain durably suppressed. The likelihood of
      distant metastasis in these patients is low despite the PSA stabilization at
      levels 1.0 ng/mL or higher and comparable to outcomes observed for those with
      lower nonrising PSA values.

PMID- 16965991
TI  - Changing the patterns of failure for high-risk prostate cancer patients by
      optimizing local control.
AB  - PURPOSE: Standard therapies for high-risk prostate cancer have resulted in
      suboptimal outcomes with both local and distant failures. Prostate-specific
      antigen (PSA) and distant metastases rates as well as biopsy outcomes are
      reported after a regimen of trimodality therapy with hormonal, radioactive seed,
      and external beam radiation therapy to demonstrate how patterns of failure are
      changed when local control is optimized. METHODS AND MATERIALS: From 1994 to
      2003, a total of 360 patients with high-risk prostate cancer were treated with
      trimodality therapy. Patients were defined as being at high risk if they
      possessed at least one of the following high-risk features: Gleason score 8 to
      10, PSA>20, clinical stage t2c to t3, or two or more intermediate risk features:
      Gleason score 7, PSA>10 to 20, or stage t2b. Patients were followed for a median
      of 4.25 years (range, 2 to 10 years). RESULTS: The actuarial 7-year freedom from
      PSA failure and freedom from distant metastases (FFDM) rates were 83% and 89%
      respectively. Patients (n=51) developing PSA failure exhibited aggressive disease
      behavior with short PSA doubling times (median, 5 months) and a 7-year freedom
      from distant metastases rate of 48%. Local control was high. The last
      posttreatment biopsy results were negative in 97% of cases (68 of 70 patients).
      In multivariate analysis, only PSA>20 predicted biochemical failure (p=0.04), and
      only seminal vesicle status predicted developing distant failure (p=0.01).
      CONCLUSIONS: Trimodality therapy results in excellent local control that alters
      patterns of failure, resulting in similar actuarial biochemical and distant
      failure rates. Most failures appear to be distant and exhibit biologically
      aggressive behavior.

PMID- 16965992
TI  - A randomized, double-blind, placebo-controlled, cross-over study to assess the
      efficacy of tadalafil (Cialis) in the treatment of erectile dysfunction following
      three-dimensional conformal external-beam radiotherapy for prostatic carcinoma.
AB  - PURPOSE: Erectile dysfunction after three-dimensional conformal external-beam
      radiotherapy (3DCRT) for prostatic carcinoma is reported in as many as 64% of
      those patients. The purpose of this study was to determine the efficacy of the
      oral drug tadalafil (Cialis) in patients with erectile dysfunction after
      radiotherapy for prostatic carcinoma. METHODS AND MATERIALS: Patients (N=358) who
      completed radiotherapy at least 12 months before the study were approached by
      mail. All patients had been treated by 3DCRT; 60 patients were included and
      entered a double-blind, placebo-controlled, cross-over study lasting 12 weeks.
      They received 20 mg of tadalafil or placebo for 6 weeks. Drug or placebo was
      taken on demand at patient's discretion, with no restrictions regarding the
      consumption of alcohol or food, at least once a week and no more than once daily.
      At 6 weeks patients crossed over to the alternative treatment. Data were
      collected using the Sexual Encounter Profile (SEP) and the International Index of
      Erectile Function (IIEF) questionnaires. Side effects were also recorded.
      RESULTS: Mean age at study entry was 69 years. All patients completed the study.
      For almost all questions of the IIEF questionnaire there was a significant
      increase in mean scores from baseline with tadalafil, but not with placebo. Sixty
      seven percent of the patients reported an improvement of erectile function with
      tadalafil (placebo: 20%), and 48% reported successful intercourse with tadalafil
      (placebo: 9%) (p<0.0001). Side effects were mild or moderate. CONCLUSIONS:
      Tadalafil is an effective treatment for erectile dysfunction after 3DCRT for
      prostatic carcinoma with successful intercourse reported in almost 50% of the
      patients, and it is well tolerated.

PMID- 16965993
TI  - Indirect MR lymphangiography of the head and neck using conventional gadolinium
      contrast: a pilot study in humans.
AB  - PURPOSE: To evaluate indirect magnetic resonance lymphangiography (MR-LAG) using
      interstitial injection of conventional gadolinium contrast (gadoteridol and
      gadopentetate dimeglumine) for delineating the primary lymphatic drainage of head
      and-neck sites. METHODS AND MATERIALS: We performed head-and-neck MR-LAG in 5
      healthy volunteers, with injection of dermal and mucosal sites. We evaluated the
      safety of the procedure, the patterns of enhancement categorized by injection
      site and nodal level, the time course of enhancement, the optimal concentration
      and volume of contrast, and the optimal imaging sequence. RESULTS: The worst side
      effects of interstitial contrast injection were brief, mild pain and swelling at
      the injected sites that were self-limited. MR-LAG resulted in consistent
      visualization of the primary lymphatic drainage pattern specific to each injected
      site, which was reproducible on repeated examinations. The best enhancement was
      obtained with injection of small volumes (0.3-0.5 mL) of either agent diluted,
      imaging within 5-15 min of injection, and a three-dimensional fast spoiled
      gradient echo sequence with magnetization transfer. CONCLUSIONS: We found head
      and-neck MR-LAG to be a safe, convenient imaging method that provides functional
      information about the lymphatic drainage of injected sites. Applied to head-and
      neck cancer, it has the potential to identify sites at highest risk of occult
      metastatic spread for radiotherapy or surgical planning, and possibly to
      visualize micrometastases.

PMID- 16965994
TI  - Pretransplant pulmonary function tests predict risk of mortality following
      fractionated total body irradiation and allogeneic peripheral blood stem cell
      transplant.
AB  - PURPOSE: To determine the value of pulmonary function tests (PFTs) done before
      peripheral blood stem cell transplant (PBSCT) in predicting mortality after total
      body irradiation (TBI) performed with or without dose reduction to the lung.
      METHODS AND MATERIALS: From 1997 to 2004, 146 consecutive patients with
      hematologic malignancies received fractionated TBI before PBSCT. With regimen A
      (n=85), patients were treated without lung dose reduction to 13.6 gray (Gy). In
      regimen B (n=35), total body dose was decreased to 12 Gy (1.5 Gy twice per day
      for 4 days) and lung dose was limited to 9 Gy by use of lung shielding. In
      regimen C (n=26), lung dose was reduced to 6 Gy. All patients received PFTs
      before treatment, 90 days after treatment, and annually. RESULTS: Median follow
      up was 44 months (range, 12-90 months). Sixty-one patients had combined
      ventilation/diffusion capacity deficits defined as both a forced expiratory
      volume in the first second (FEV1) and a diffusion capacity of carbon dioxide
      (DLCO)<100% predicted. In this group, there was a 20% improvement in one-year
      overall survival with lung dose reduction (70 vs. 50%, log-rank test p=0.042).
      CONCLUSION: Among those with combined ventilation/diffusion capacity deficits,
      lung dose reduction during TBI significantly improved survival.

PMID- 16965995
TI  - Enhancement of radiosensitivity by dual inhibition of the HER family with ZD1839
      ("Iressa") and trastuzumab ("Herceptin").
AB  - PURPOSE: The aims of this study were twofold: (1) to examine the effects of dual
      inhibition of 2 members of the HER family, the epidermoid growth factor receptor
      (EGFR) and HER2/neu, by gefitinib (ZD1839) and trastuzumab on radiosensitivity;
      and (2) to explore the molecular mechanism of radiosensitization especially
      focusing on the survival signal transduction pathways by using A431 human vulvar
      squamous carcinoma cells expressing EGFR and HER2/neu. METHODS AND MATERIALS: The
      effects of inhibitors on the radiation-induced activation of EGFR and/or
      HER2/neu, and the intracellular proteins that are involved in their downstream
      signaling, were quantified by the Western blot. Radiosensitizing effects by the
      blockage of EGFR and/or HER2/neu were determined by a clonogenic assay. RESULTS:
      Radiation-induced activation of the EGFR and HER2/neu was inhibited with ZD1839
      and/or trastuzumab. ZD1839 also inhibited the radiation-induced phosphorylation
      of HER2/neu. Radiation in combination with the HER family inhibitors inhibited
      the activation of Akt and MEK1/2, the downstream survival signaling of the HER
      family. ZD1839 enhanced radiosensitivity with a dose-modifying factor (DMF) (SF3)
      of 1.45 and trastuzumab did so with a DMF (SF3) of 1.11. Simultaneous blockade of
      EGFR and HER2/neu induced a synergistic radiosensitizing effect with a DMF (SF3)
      of 2.29. CONCLUSIONS: The present data suggest that a dual EGFR and HER2/neu
      targeting may have potential for radiosensitization in tumors in which both of
      these pathways are active.

PMID- 16965996
TI  - DNA damage repair and genetic polymorphisms: assessment of individual sensitivity
      and repair capacity.
AB  - PURPOSE: To study the repair capacity after X-ray irradiation in human peripheral
      blood cells of healthy subjects, in relation to their genotypes. METHODS AND
      MATERIALS: The peripheral blood of 50 healthy subjects was irradiated in vitro
      with 2 Gy of X rays and the induced DNA damage was measured by Comet assay
      immediately after irradiation. DNA repair was detected by analyzing the cells at
      defined time intervals after the exposure. Furthermore, all subjects were
      genotyped for XRCC1, OGG1, and XPC genes. RESULTS: After X-ray irradiation,
      persons bearing XRCC1 homozygous variant (codon 399) genotype exhibited
      significantly lower Tail DNA values than those bearing wild-type and heterozygous
      genotypes. These results are also confirmed at 30 and 60 min after irradiation.
      Furthermore, XPC heterozygous subjects (variant codon 939) showed lower residual
      DNA damage 60 min after irradiation compared with wild-type and homozygous
      genotypes. CONCLUSION: The results of the present study show that polymorphisms
      in DNA repair genes could influence individual DNA repair capacity.

PMID- 16965998
TI  - Anti-inflammatory effects of low-dose radiotherapy in an experimental model of
      systemic inflammation in mice.
AB  - PURPOSE: The aim of this study was to determine the effects of low-dose
      radiotherapy (LD-RT) on the inflammatory response and to characterize the
      potential mechanisms underlying these effects. METHODS AND MATERIALS: Mice were
      irradiated with 0.1, 0.3, 0.6 Gy, or sham radiation before lipopolysaccharide
      (LPS) challenge. Leukocyte-endothelial cell interactions in intestinal venules
      were assessed using intravital microscopy. Intercellular adhesion molecule-1
      (ICAM-1) expression was determined using radiolabeled antibodies 5 h after
      irradiation. Production of transforming growth factor-beta1 (TGF-beta1) was
      measured by enzyme-linked immunosorbent assay and its in vivo functional
      relevance by immunoneutralization. RESULTS: Compared with vehicle treated
      animals, LPS induced a marked increase in leukocyte adhesion (0.13+/-0.59 vs.
      5.89+/-1.03, p<0.0001) in intestinal venules. The number of adherent leukocytes
      was significantly reduced by the 3 doses of LD-RT tested; the highest inhibition
      was observed with 0.3 Gy (0.66+/-1.96, p<0.0001). LPS-induced ICAM-1 upregulation
      was not modified by LD-RT. Circulating levels of TGF-beta1 were significantly
      increased in response to LD-RT in controls and LPS challenged animals.
      Neutralization of TGF-beta1 partially restored LPS-induced adhesion (4.83+/-1.41,
      p<0.05). CONCLUSIONS: LD-RT has a significant anti-inflammatory effect,
      inhibiting leukocyte recruitment, which is maximal at 0.3 Gy. This effect results
      in part from increased TGF-beta1 production and is not related to modulation of
      ICAM-1 expression.

PMID- 16965997
TI  - Orazipone, a locally acting immunomodulator, ameliorates intestinal radiation
      injury: a preclinical study in a novel rat model.
AB  - PURPOSE: Intestinal radiation injury (radiation enteropathy) is relevant to
      cancer treatment, as well as to radiation accidents and radiation terrorism
      scenarios. This study assessed the protective efficacy of orazipone, a locally
      acting small molecule immunomodulator. METHODS AND MATERIALS: Male rats were
      orchiectomized, a 4-cm segment of small bowel was sutured to the inside of the
      scrotum, a proximal anteperistaltic ileostomy was created for intraluminal drug
      administration, and intestinal continuity was re-established by end-to-side
      anastomosis. After three weeks postoperative recovery, the intestine in the
      "scrotal hernia" was exposed locally to single-dose or fractionated X-radiation.
      Orazipone (30 mg/kg/day) or vehicle was administered daily through the ileostomy,
      either during and after irradiation, or only after irradiation. Structural,
      cellular, and molecular aspects of intestinal radiation toxicity were assessed
      two weeks after irradiation. RESULTS: Orazipone significantly ameliorated
      histologic injury and transforming growth factor-beta immunoreactivity levels,
      both after single-dose and fractionated irradiation. Intestinal wall thickness
      was significantly reduced after single-dose and nonsignificantly after
      fractionated irradiation. Mucosal surface area and numbers of mast cells were
      partially restored by orazipone after single-dose irradiation. CONCLUSIONS: This
      work (1) demonstrates the utility of the ileostomy rat model for intraluminal
      administration of response modifiers in single-dose and fractionated radiation
      studies; (2) shows that mucosal immunomodulation during and/or after irradiation
      ameliorates intestinal toxicity; and (3) highlights important differences between
      single-dose and fractionated radiation regimens.

PMID- 16965999
TI  - Accuracy of single-session extracranial radiotherapy for simple shaped lung tumor
      or metastasis using fast 3-D CT treatment planning.
AB  - BACKGROUND: This study is situated in the area of measuring set-up accuracy and
      time periods of single-session extracranial radiotherapy (SSRT) for simple-shaped
      targets (e.g., spherical or rotational symmetrical) definitively located in the
      peripheral lung. METHODS AND MATERIALS: After adaptation of the stereotactic body
      frame, the patient has to remain in the vacuum pillow during planning computed
      tomography (CT), fast three-dimensional (3-D) treatment planning, and direct
      irradiation after verification. Fast preplanning is performed by using virtual
      simulation software to accelerate the method. RESULTS: In our new procedure, SSRT
      is applied in approximately 1.5 h. The mean setup accuracy vector was 2.4+/-0.7
      mm in the range of 1.34 to 4 mm. Mean intrafractional patient movement in the
      stereotactic body frame before and after radiation was 0.70 mm+/-0.5 mm and
      0.76+/-0.76 mm in the range of 0 to 2.8 mm. Mean time period steps were measured
      at (1) planning CT with 3-D treatment planning: 76+/-12 min; (2) irradiation and
      verification: 33+/-7 min; and (3) complete procedure duration: 109+/-11 min
      (range, 89-169). CONCLUSIONS: The main difference between the positioning
      technique of SSRT and that of conventional extracranial radiosurgery is the
      tighter patient fixation, which guarantees minimal patient movement. The main
      advantages are procedure acceleration and omission of CT simulation. SSRT is a
      preliminary stage of real-time treatment.

PMID- 16966001
TI  - Daily variations in the position of the prostate bed in patients with prostate
      cancer receiving postoperative external beam radiation therapy.
AB  - PURPOSE: The aim of this study was to evaluate the extent of the variation in the
      position of the prostate bed with respect to the bony anatomy. METHODS AND
      MATERIALS: Four patients were treated to 70 Gy in 35 fractions. Before each
      fraction, a megavoltage computed tomography (CT) of the prostate bed was
      obtained, resulting in a total of 140 CT studies. Retrospectively, each CT scan
      was aligned to the simulation kilovoltage scan based on bony anatomy and the
      prostate bed. The difference between the 2 alignments was calculated for each
      scan. RESULTS: The average differences (+/-1 SD) between the two alignments were
      0.06+/-0.37, 0.10+/-0.86, and 0.39+/-1.27 mm in the lateral, longitudinal (SI),
      and vertical (AP) directions, respectively. Laterally, there was no
      difference>or=3 mm. The cumulative frequency of SI differences were as follows;
      >or=3 mm: 3%, >or=4 mm: 1%, and >or=5 mm: 1% (maximum: 5 mm). The cumulative
      frequency of AP differences were as follows; >or=3 mm: 7%, and >or=4 mm: 3%
      (maximum: 4 mm). CONCLUSION: In patients with prostate cancer receiving
      postoperative radiotherapy, the prostate bed motion relative to the pelvic bony
      anatomy is of a relatively small magnitude. Significant motion (>or=3 mm) is
      infrequent. However, small differences between the prostate bed and the bony
      anatomy still exist. This might have implications on treatment margins when daily
      alignment on bony anatomy is performed.

PMID- 16966000
TI  - Impact of pelvic nodal irradiation with intensity-modulated radiotherapy on
      treatment of prostate cancer.
AB  - PURPOSE: The aim of this study was to evaluate the feasibility of treating the
      pelvic lymphatic regions during prostate intensity-modulated radiotherapy (IMRT)
      with respect to our routine acceptance criteria. METHODS AND MATERIALS: A series
      of 10 previously treated prostate patients were randomly selected and the pelvic
      lymphatic regions delineated on the fused magnetic resonance/computed tomography
      data sets. A targeting progression was formed from the prostate and proximal
      seminal vesicles only to the inclusion of all pelvic lymphatic regions and
      presacral region resulting in 5 planning scenarios of increasing geometric
      difficulty. IMRT plans were generated for each stage for two accelerator
      manufacturers. Dose volume histogram data were analyzed with respect to dose to
      the planning target volumes, rectum, bladder, bowel, and normal tissue. Analysis
      was performed for the number of segments required, monitor units, "hot spots,"
      and treatment time. RESULTS: Both rectal endpoints were met for all targets.
      Bladder endpoints were not met and the bowel endpoint was met in 40% of cases
      with the inclusion of the extended and presacral lymphatics. A significant
      difference was found in the number of segments and monitor units with targeting
      progression and between accelerators, with the smaller beamlets yielding poorer
      results. Treatment times between the 2 linacs did not exhibit a clinically
      significant difference when compared. CONCLUSIONS: Many issues should be
      considered with pelvic lymphatic irradiation during IMRT delivery for prostate
      cancer including dose per fraction, normal structure dose/volume limits, planning
      target volumes generation, localization, treatment time, and increased radiation
      leakage. We would suggest that, at a minimum, the endpoints used in this work be
      evaluated before beginning IMRT pelvic nodal irradiation.

PMID- 16966002
TI  - Comparison of MRI-based and CT/MRI fusion-based postimplant dosimetric analysis
      of prostate brachytherapy.
AB  - PURPOSE: The aim of this study was to compare the outcomes between magnetic
      resonance imaging (MRI)-based and computed tomography (CT)/MRI fusion-based
      postimplant dosimetry methods in permanent prostate brachytherapy. METHODS AND
      MATERIALS: Between October 2004 and March 2006, a total of 52 consecutive
      patients with prostate cancer were treated by brachytherapy, and postimplant
      dosimetry was performed using CT/MRI fusion. The accuracy and reproducibility
      were prospectively compared between MRI-based dosimetry and CT/MRI fusion-based
      dosimetry based on the dose-volume histogram (DVH) related parameters as
      recommended by the American Brachytherapy Society. RESULTS: The prostate volume
      was 15.97+/-6.17 cc (mean+/-SD) in MRI-based dosimetry, and 15.97+/-6.02 cc in
      CT/MRI fusion-based dosimetry without statistical difference. The prostate V100
      was 94.5% and 93.0% in MRI-based and CT/MRI fusion-based dosimetry, respectively,
      and the difference was statistically significant (p=0.002). The prostate D90 was
      119.4% and 114.4% in MRI-based and CT/MRI fusion-based dosimetry, respectively,
      and the difference was statistically significant (p=0.004). CONCLUSION: Our
      current results suggested that, as with fusion images, MR images allowed accurate
      contouring of the organs, but they tended to overestimate the analysis of
      postimplant dosimetry in comparison to CT/MRI fusion images. Although this MRI
      based dosimetric discrepancy was negligible, MRI-based dosimetry was acceptable
      and reproducible in comparison to CT-based dosimetry, because the difference
      between MRI-based and CT/MRI fusion-based results was smaller than that between
      CT-based and CT/MRI fusion-based results as previously reported.

PMID- 16966003
TI  - Quality assurance of I-125 seeds for prostate brachytherapy using an imaging
      plate.
AB  - PURPOSE: OncoSeed is delivered in a sterile environment in the form of a
      cartridge, so it is impractical to resterilize and reload seeds after
      calibration. We investigated a new method using an imaging plate dosimetry system
      to characterize all seeds in the OncoSeed cartridge in a sterile environment.
      METHODS AND MATERIALS: Seeds within the cartridge were placed on an imaging
      plate, and the imaging plate irradiated. To remove scatter radiation, and improve
      spatial resolution of seed images, we used X-ray parallel cross grids. The
      irradiated imaging plate was scanned using a Bio-imaging Analyzer System, and
      radioactivity intensities of seed images were given in counts. Counts could be
      translated to profiles, and each seed within the cartridge was analyzed. RESULTS:
      Results showed a good correlation between counts and total radioactivity of the
      seeds within the cartridge. Thus, using a least-squares line, it was possible to
      characterize a cartridge with unknown apparent activity. By analyzing the
      profiles, it was possible not only to detect a miscalibrated seed in the
      cartridge from its relative difference in counts, but also to identify its
      position in the cartridge. No significant changes in counts were seen between
      sterile and nonsterile environments. CONCLUSION: Using an imaging plate dosimetry
      system, all seeds in a cartridge could be characterized in a sterile environment.

PMID- 16966004
TI  - Assessment of residual error in liver position using kV cone-beam computed
      tomography for liver cancer high-precision radiation therapy.
AB  - PURPOSE: To evaluate the residual error in liver position using breath-hold
      kilovoltage (kV) cone-beam computed tomography (CT) following on-line orthogonal
      megavoltage (MV) image-guided breath-hold liver cancer conformal radiotherapy.
      METHODS AND MATERIALS: Thirteen patients with liver cancer treated with 6
      fraction breath-hold conformal radiotherapy were investigated. Before each
      fraction, orthogonal MV images were obtained during exhale breath-hold, with
      repositioning for offsets>3 mm, using the diaphragm for cranio-caudal (CC)
      alignment and vertebral bodies for medial-lateral (ML) and anterior posterior
      (AP) alignment. After repositioning, repeat orthogonal MV images, orthogonal kV
      fluoroscopic movies, and kV cone-beam CTs were obtained in exhale breath-hold.
      The cone-beam CT livers were registered to the planning CT liver to obtain the
      residual setup error in liver position. RESULTS: After repositioning, 78
      orthogonal MV image pairs, 61 orthogonal kV image pairs, and 72 kV cone-beam CT
      scans were obtained. Population random setup errors (sigma) in liver position
      were 2.7 mm (CC), 2.3 mm (ML), and 3.0 mm (AP), and systematic errors (Sigma)
      were 1.1 mm, 1.9 mm, and 1.3 mm in the superior, medial, and posterior
      directions. Liver offsets>5 mm were observed in 33% of cases; offsets>10 mm and
      liver deformation>5 mm were observed in a minority of patients. CONCLUSIONS:
      Liver position after radiation therapy guided with MV orthogonal imaging was
      within 5 mm of planned position in the majority of patients. kV cone-beam CT
      image guidance should improve accuracy with reduced dose compared with orthogonal
      MV image guidance for liver cancer radiation therapy.

PMID- 16966006
TI  - In regards to Glatstein: the whirligig of time (Int J Radiat Oncol Biol Phys
      2006;65:322-323).

PMID- 16966007
TI  - External beam partial-breast radiotherapy: crucial differences between NYU 00-23
      and RTOG 0319: in regard to Vicini et al. (Int J Radiat Oncol Biol Phys
      2005;63:1531-1537).

PMID- 16966009
TI  - Linear quadratic modeling of increased late normal-tissue effects in special
      clinical situations: in regard to Jones et al. (Int J Radiat Oncol Biol Phys
      2006;64:948-953).

PMID- 16966010
TI  - Optimal CTV margins for gross metastatic neck nodes.

PMID- 16966012
TI  - In vivo dose measurements of extra dose from cone-beam computed tomography.

PMID- 16966013
TI  - Hyperthermia is effective in improving clinical radiotherapy results.

PMID- 16966017
TI  - Lupus erythematosus: systemic and cutaneous manifestations.
AB  - Skin and joint involvements are the most commonly occurring manifestations of
      systemic lupus erythematosus. There are 3 forms of cutaneous lupus: chronic
      cutaneous (discoid) lupus, subacute cutaneous lupus, and acute cutaneous lupus.
      Joint manifestations are usually not associated with warmth of the joints and may
      be only associated with pain and swelling. Painful or swollen joints respond
      rapidly to small or moderate doses of corticosteroids, whereas cutaneous
      manifestations usually respond to antimalarial drugs. Anti-Ro is associated
      closely with a photosensitive rash and with subacute lupus.

PMID- 16966018
TI  - Dermatomyositis.
AB  - Dermatomyositis is one of the idiopathic inflammatory myopathies. It is
      characterized clinically by progressive symmetrical proximal muscle weakness and
      a characteristic rash. There are patients with rash who have little or no muscle
      disease. Although the process primarily attacks the skin and the muscles, it is a
      systemic disease with frequent manifestations in the gastrointestinal tract and
      pulmonary system. Dermatomyositis has been linked to internal malignancy in
      somewhere between 15% and 25%. Therapy for the muscle disease includes systemic
      corticosteroids with or without an immunosuppressive agent. Therapy of the skin
      disease begins with photoprotection and topical corticosteroids, but also
      includes the use of antimalarial agents and immunomodulatory therapies.

PMID- 16966019
TI  - Systemic and localized scleroderma.
AB  - Sclerosing conditions of the skin are manifested by a full spectrum of
      presentations that includes skin-limited forms as well as those which can involve
      internal organs and result in death. At this point, we are just beginning to
      understand the mechanisms of tissue fibrosis, and it is likely that the fibrotic
      processes are a heterogeneous group of disorders in which perturbation of
      multiple molecular pathways, including vascular and immunologically mediated
      pathways, can lead to fibrosis. We now have some moderately effective therapies
      for vascular aspects of systemic sclerosis (eg, bosentan for pulmonary arterial
      hypertension, calcium-channel blockers for Raynaud's, or angiotensin-converting
      enzyme inhibitors for renal crisis). We also are beginning to find treatments
      interrupting the immunologic pathways that manifest as systemic sclerosis (eg,
      methotrexate for the skin or cyclophosphamide for the lungs). The basic process
      of fibrosis, however, awaits proven, effective therapy.

PMID- 16966020
TI  - Sjogren's syndrome in dermatology.
AB  - Sjogren's Syndrome (SS) is a systemic autoimmune disease characterized by dry
      eyes (keratoconjunctivis sicca) and dry mouth (xerostomia). To fulfill diagnostic
      criteria, patients must have objective signs of dryness on examination and
      laboratory confirmation of an autoimmune process as evidenced by a positive
      autoantibody to SS-A antigen or a characteristic lip biopsy. SS may exist as a
      primary condition or in association with other systemic autoimmune disorders
      (termed secondary SS) such as rheumatoid arthritis, systemic lupus erythematous
      (SLE), progressive systemic sclerosis (scleroderma), or dermatomyositis.
      Exclusions to the diagnosis include pre-existing lymphoma, hepatitis C or HIV
      infection. Pathogenesis involves both genetic (especially HLA-DR) and
      environmental factors. Both T-cells and B-cells are involved in the generation of
      cytokines and chemokines within the glands. The epithelial cells of the glands
      also play a role in pathogenesis. The dermatologic manifestations range from
      drynessness (sicca) and its complications to vasculitis. There is a significant
      overlap in the clinical manifestations, as well as treatment, of SS and SLE.
      However, SS patients require special attention to the complications of ocular
      dryness (keratocojunctivitis sicca and blepharitis) and oral dryness (rapid tooth
      loss and oral candidiasis) SS patients have a markedly increased risk of lymphoma
      and enlarged lymph nodes or persistently enlarged parotid/submandibular glands
      that require further evaluation.

PMID- 16966021
TI  - Cutaneous vasculitis: diagnosis and management.
AB  - Vasculitis is histologically defined as inflammatory cell infiltration and
      destruction of blood vessels. Vasculitis is classified as primary (idiopathic,
      eg, cutaneous leukocytoclastic angiitis, Wegener's granulomatosis) or secondary,
      a manifestation of connective tissue diseases, infections, adverse drug
      eruptions, or a paraneoplastic phenomenon. Cutaneous vasculitis, manifested as
      urticaria, purpura, hemorrhagic vesicles, ulcers, nodules, livedo, infarcts, or
      digital gangrene, is a frequent and often significant component of many systemic
      vasculitic syndromes such as lupus or rheumatoid vasculitis and antineutrophil
      cytoplasmic antibody-associated primary vasculitic syndromes such as Churg
      Strauss syndrome. In most instances, cutaneous vasculitis represents a self
      limited, single-episode phenomenon, the treatment of which consists of general
      measures such as leg elevation, warming, avoidance of standing, cold temperatures
      and tight fitting clothing, and therapy with antihistamines, aspirin, or
      nonsteroidal anti-inflammatory drugs. More extensive therapy is indicated for
      symptomatic, recurrent, extensive, and persistent skin disease or coexistence of
      systemic disease. For mild recurrent or persistent disease, colchicine and
      dapsone are first-choice agents. Severe cutaneous and systemic disease requires
      more potent immunosuppression (prednisone plus azathioprine, methotrexate,
      cyclophosphamide, cyclosporine, or mycophenolate mofetil). In cases of refractory
      vasculitis, plasmapheresis and intravenous immunoglobulin are viable
      considerations. The new biologic therapies that work via cytokine blockade or
      lymphocyte depletion such as tumor alpha inhibitor infliximab and the anti-B-cell
      antibody rituximab, respectively, are showing benefit in certain settings such as
      Wegener's granulomatosis, antineutrophil cytoplasmic antibody-associated
      vasculitis, Behcet's disease, and cryoglobulinemic vasculitis.

PMID- 16966022
TI  - Rheumatoid arthritis in dermatology.
AB  - Rheumatoid arthritis (RA) is a chronic progressive disorder characterized by
      symmetric inflammatory arthritis in association with systemic symptoms. Although
      considered a "joint disease," RA is associated with involvement in diverse organ
      systems, including the skin. Common manifestations include Raynaud phenomenon,
      rheumatoid nodules, and rheumatoid vasculitis. As with other extra-articular
      manifestations, dermatologic involvement tends to occur in patients with more
      severe RA. In addition to manifestations related to the disease, there are also
      sundry dermatologic reactions related to the medications used to treat RA.
      Understanding the etiology and therapy for cutaneous manifestations of RA will
      help optimize patient care.

PMID- 16966023
TI  - Psoriasis and psoriatic arthritis: clinical features and disease mechanisms.
AB  - Psoriasis is a chronic skin disorder affecting approximately 1% to 3% of the
      world's population. A considerable proportion of patients with psoriasis will
      develop a form of inflammatory arthritis known as psoriatic arthritis whose
      prevalence is poorly defined. Significant advances have been made in determining
      the pathophysiology of both of these diseases, with recent findings strongly
      implicating T cells and inflammatory cytokines such as tumor necrosis factor
      alpha in their pathogenesis. There exists an increasing array of therapies to
      benefit both skin and musculoskeletal manifestations. Newer therapies, such as
      the biologics, are providing more targeted approaches with potentially fewer
      systemic toxicities, providing control of disease symptoms and inhibiting
      progressive joint damage in those with arthritis, as well as improving long-term
      function and quality of life.

PMID- 16966025
TI  - Why not Nichols chemosurgery?

PMID- 16966026
TI  - Juan Di Prisco, MD (1918-1994).

PMID- 16966027
TI  - Sunscreen savvy: why do sunscreens fail to protect?

PMID- 16966028
TI  - Outcome following surgical therapy for gastrointestinal stromal tumors.
AB  - We have pursued an approach of complete resection for patients with
      gastrointestinal stromal tumors (GISTs), including multivisceral resection, for
      patients with disease involving adjacent organs. We have also extended the limits
      of resection to include patients with metastatic disease who were treated with
      imatinib mesylate. The aim of this study is to report the outcomes and prognostic
      factors associated with this clinical approach. Study subjects were identified
      using the pathology database at our institution; for inclusion in the study
      group, patients must have undergone surgical resection for a KIT-positive
      gastrointestinal stromal tumor between January 1992 and March 2004. We calculated
      survival by using the Kaplan-Meier method. Univariate and multivariate analysis
      was performed using log-rank analysis and the Cox proportional hazards model.
      Thirty-four patients met the study criteria. Fifty-nine percent of patients had
      GISTs of gastric origin, 20.6% had duodenal GISTs, and the remainder was
      comprised of a variety of other sites. Twenty-two (64.7%) patients underwent
      single-organ resection, and 12 patients (35.3%) underwent multivisceral
      resection. Estimated actuarial survival at 5 years was 65.2%. Seven patients
      (five patients with metastases, one patient with locally advanced disease, and
      one patient with organ-confined disease) received imatinib mesylate. Independent
      predictors of poor survival included incomplete resection, metastatic disease at
      presentation, and high mitotic index. Mitotic index and the presence of
      metastases remain the primary predictors of postoperative survival. Complete
      surgical resection, even if multivisceral resection is required, is associated
      with improved survival.

PMID- 16966030
TI  - Post-gastric bypass hyperinsulinism with nesidioblastosis: subtotal or total
      pancreatectomy may be needed to prevent recurrent hypoglycemia.
AB  - Symptomatic hyperinsulinemic hypoglycemia and pancreatic nesidioblastosis have
      recently been described in a small series of patients after gastric bypass
      surgery for morbid obesity. In the limited published reports of patients with
      this condition, hyperinsulinism and nesidioblastosis have been managed with
      distal or subtotal pancreatectomy, with the extent of resection guided by calcium
      angiography. However, nesidioblastosis may involve the pancreas diffusely, and
      limited pancreatic resections may predispose patients to further hypoglycemic
      episodes. We have treated two patients with refractory hyperinsulinism and
      symptomatic hypoglycemia after successful gastric bypass surgery. One patient
      underwent an approximately 80% pancreatectomy with good results but subsequently
      experienced recurrent drop attacks and fainting from hyperinsulinism; a
      completion pancreatectomy via a pancreaticoduodenectomy was then required. A
      second patient had profound hyperinsulinemic hypoglycemia and was treated
      successfully with a subtotal (95%) pancreatectomy. Our experience, the third
      published report of post-gastric bypass nesidioblastosis, suggests that the risk
      of recurrent symptomatic hyperinsulinism after limited pancreatectomy is
      significant and relative euglycemia may be achieved with subtotal or total
      pancreatectomy.

PMID- 16966029
TI  - Postoperative morbidity and long-term survival after pancreaticoduodenectomy with
      superior mesenterico-portal vein resection.
AB  - The role of superior mesenteric-portal vein resection (SM-PVR) for vein invasion
      or tumor adherence during pancreatoduodenectomy (PD) is still under debate. We
      investigated morbidity, mortality, and long-term survival in patients who
      underwent PD with or without SM-PVR. Between July 1994 and December 2004, 222 PD
      (78% pylorus preserving, 19% Whipple, and 3% total pancreatectomy) were performed
      for malignant disease. Fifty-three patients (24%) had PD with SM-PVR. Sixty-eight
      percent of the venous resections were performed as wedge excisions and 32% as
      segmental resections. Long-term survival was analyzed in 165 patients with
      pancreatic (n = 110), ampullary (n = 33), or distal bile (n = 22) duct cancer
      using univariate (log-rank) and multivariate (Cox regression) methods. In
      patients undergoing PD with SM-PVR and conclusive histologic examination of the
      resected vein specimen (n = 42), 60% had true tumor involvement of the venous
      wall, whereas 40% had no proven tumor infiltration. In the complete study group,
      negative resection margins were obtained in 69% of patients with SM-PVR and in
      79% of patients without SM-PVR (P = 0.09). Median duration of surgery was 500
      minutes (SM-PVR) versus 440 minutes (no SM-PVR; P < 0.001). Volume of
      intraoperatively transfused blood was 600 ml (median) in both groups.
      Postoperative surgical complications/mortality occurred in 23%/3.8% (SM-PVR)
      versus 35%/4.1% (no SM-PVR); P = 0.09/0.9. Analysis of long-term survival in all
      165 patients included 41 with SM-PVR. Five-year survival rates were 15% in cancer
      of the pancreatic head, 22% in ampullary cancer, and 24% in distal bile duct
      cancer (P = 0.02). Long-term survival was not influenced by the need for SM-PVR
      in any of the different tumor entities. In multivariate analysis, a positive
      resection margin (P < 0.01, relative risk [RR]: 1.8, 95% confidence interval
      [CI]: 1.2-2.7), a histologically undifferentiated tumor (P = 0.01, RR: 1.7, 95%
      CI: 1.1-2.5), and the tumor entity (P < 0.01) were significant predictors of
      survival. Univariate survival analysis of the 110 patients with cancer of the
      pancreatic head revealed that a histologically undifferentiated tumor (P = 0.05)
      and positive resection margins (P = 0.02) were associated with a poorer survival.
      In multivariate analysis, the resection margin (P = 0.02, RR: 5.1, 95% CI: 1.1
      2.8) and a histologically undifferentiated tumor (P = 0.05, RR: 3.8, 95% CI: 1.0
      2.5) significantly influenced survival. After PD, perioperative morbidity and
      long-term survival in patients with SM-PVR were similar to those of patients
      without vein resection. In case of tumor adherence or infiltration, combined
      resection of the pancreatic head and the vein should always be considered in the
      absence of other contraindications for resection.

PMID- 16966031
TI  - Anti-inflammatory effects of PPAR-gamma agonists directly correlate with PPAR
      gamma expression during acute pancreatitis.
AB  - Peroxisome proliferator-activated receptors (PPARs) are ligand-inducible
      transcription factors that regulate cellular energy and lipid metabolism. PPAR
      gamma agonists also have potent anti-inflammatory properties through down
      regulation of early inflammatory response genes. The role of PPAR-gamma in acute
      pancreatitis has not been adequately examined. In this study, we determined the
      effect of PPAR-gamma agonists on the severity of pancreatitis and sought to
      correlate PPAR-gamma expression in pancreatic acinar cells and the severity of
      acute pancreatitis in vivo. Acute pancreatitis was induced in mice by
      hyperstimulation with the cholecystokinin analog, cerulein. PPAR-gamma agonists
      were administered by intraperitoneal injection 15-30 minutes before induction of
      pancreatitis (pretreatment) or at various times after induction of pancreatitis
      (treatment). Pancreata and serum were harvested over the course of 24 hours.
      Serum amylase activity and glucose levels were measured. Pancreata were used for
      histological evaluation as well as protein and mRNA analysis. Pretreatment of
      mice with the PPAR-gamma agonists 15-deoxy-Delta12, 14-prostaglandin J(2), or
      troglitazone significantly reduced the severity of pancreatitis in a dose
      dependent manner. This reduction was indicated by reduced serum amylase activity
      and histological damage (leukocyte infiltration, vacuolization, and necrosis).
      Although cerulein decreased PPAR-gamma expression in the pancreas, pretreatment
      with agonists maintained PPAR-gamma expression early in acute pancreatitis. The
      expression of PPAR-gamma inversely correlated with pancreatitis severity and
      expression of the proinflammatory cytokines, interleukin-6, and tumor necrosis
      factor-alpha. Treatment with troglitazone after the induction of pancreatitis
      reduced serum amylase activity. The results suggest that PPAR-gamma plays a
      direct role in the inflammatory cascade during the early events of acute
      pancreatitis. Our data are the first to demonstrate that PPAR-gamma agonists
      represent a promising therapeutic strategy for acute pancreatitis.

PMID- 16966032
TI  - Postoperative acute pancreatitis as a major determinant of postoperative delayed
      gastric emptying after pancreaticoduodenectomy.
AB  - The aim of this study was to prospectively analyze the possible association of
      delayed gastric emptying and postoperative pancreatic complications after
      pancreaticoduodenectomy. Although hospital mortality after
      pancreaticoduodenectomy is minimal, morbidity is still high; delayed gastric
      emptying is one of the most frequent complications. Thirty-nine consecutive
      patients undergoing pancreaticoduodenectomy were included in this study: 14
      females and 25 males (median age 65 years; range, 7-82). Delayed gastric emptying
      was defined as the need for a nasogastric tube or recurrent vomiting that
      prevented normal feeding on the 10th postoperative day. Blood analysis was
      performed on postoperative days 4, 6, and 10; Gastrografin examination on day 6;
      CT scan on days 2 and 5; and drain amylases were measured on day 5. Pancreatitis
      was defined as pancreatitis changes in CT scan interpreted by an experienced
      radiologist without knowing other data. Pancreatic fistula was defined according
      to the recent international recommendations. We had no mortality. Twelve patients
      (31%) developed delayed gastric emptying. Surgical (9/12 vs. 5/27; P = 0.001) but
      not medical complications occurred more often in the delayed gastric emptying
      group. Of the single complications, postoperative CT-detected pancreatitis (6/12
      vs. 4/27; P = 0.03) and postoperative pancreatic fistula (5/12 vs. 1/27; P =
      0.0007) were significantly associated with delayed gastric emptying compared with
      the patients without delayed gastric emptying. This pancreatitis was already
      detected in CT scan on day 2 in most patients (6/10, 60%). In delayed gastric
      emptying patients, the only parameters in blood analysis that differed
      significantly from patients without this complication were serum amylase activity
      (mean +/- SEM, 715 +/- 205 vs. 152 +/- 70 IU/L; P = 0.02), blood leukocyte count
      (16 +/- 2 vs. 9 +/- 0.6 x 10(9)/L; P = 0.007) and serum C-reactive protein (CRP)
      concentration (144 +/- 28 vs. 51 +/- 14 mg/L, P = 0.01). Postoperative pancreatic
      (subclinical) fistula was also associated with postoperative pancreatitis (6/10
      vs. 0/29; P = 0.003). Preoperative coronary artery disease (OR = 16; 95% CI, 1.0
      241; P = 0.05) and soft pancreatic texture at operation (OR = 9; 95% CI, 1.4-52;
      P = 0.02) were significant risk factors for the development of postoperative
      pancreatitis. The diagnosis of delayed gastric emptying after
      pancreaticoduodenectomy often follows postoperative pancreatitis. Delayed gastric
      emptying is also associated with postoperative pancreatic fistula, for which this
      pancreatitis seems to be a risk factor. Preoperative coronary artery disease and
      soft texture of the pancreas are significant risk factors for postoperative CT
      detected pancreatitis.

PMID- 16966033
TI  - Carcinoma of the papilla of Vater: are endoscopic appearance and endoscopic
      biopsy discordant?
AB  - Carcinoma of the papilla of Vater is classified as periampullary cancer
      representing 5% of all gastrointestinal tract malignancies. Early and accurate
      diagnosis is important for those patients with a tumor of the papilla, as the
      prognosis is more favorable than in other periampullary neoplasms. Endoscopically
      obtained biopsies from suspicious papillae can detect an early tumor, although
      even for skilled pathologists it is often difficult to differentiate carcinomas
      from noninvasive lesions on the basis of forceps biopsies. The purpose of this
      study was to assess the preoperative diagnostic accuracy of duodenoscopy
      appearance and biopsy in all cases with suspicion of tumor. Thirty patients with
      suspicion of carcinoma of the papilla of Vater and with final diagnosis
      established by pancreatoduodenectomy were included in this retrospective study.
      In each case, a comparison was made between endoscopic biopsy and duodenoscopic
      appearance. Duodenoscopic appearance sensitivity and accuracy for malignancy were
      86% and 83%, respectively, whereas endoscopic biopsy sensitivity and accuracy
      were 65% and 67%, respectively. Although preoperative diagnosis of carcinoma of
      the papilla of Vater is useful for making therapeutic decisions, the diagnostic
      value of the endoscopic appearance was superior to endoscopic biopsy in this
      series.

PMID- 16966034
TI  - Management and outcome in patients with Klatskin-mimicking lesions of the biliary
      tree.
AB  - The preoperative and even intraoperative differentiation between benign and
      malignant strictures at the hepatic hilum remains difficult. The aim of this
      study was to assess clinical, radiologic, intraoperative, and histopathologic
      findings; surgical treatment; and outcome of patients with Klatskin mimicking
      benign lesions. Of 49 consecutive patients who were operated on the initial
      preoperative radiologic diagnosis of hilar adenocarcinoma (Klatskin tumor), 7
      (14%) had benign conditions after final histopathologic diagnosis. Pretreatment
      work-up, therapy, and outcome of these patients were analyzed. Based on
      preoperative clinical symptoms, imaging assessment, and CA19-9 values, all seven
      patients were classified as having malignant neoplasms. At laparotomy, the tumors
      of six patients were judged to be malignant. Five patients underwent hilar
      resection and concomitant liver resection, and two patients underwent hilar
      resection alone. There were no operative deaths. The definitive histopathologic
      examination showed severe cholangitis with extensive periductal fibrosis in all
      patients. After a median follow-up of 32 months, all patients are well. Clinical
      presentation and imaging assessment were similar for Klatskin tumors and benign
      fibrosing disease; therefore, an aggressive resectional approach is justified in
      any patient with suspicious obstruction of the liver hilum.

PMID- 16966035
TI  - Hepatic vein injury during laparoscopic cholecystectomy: the unappreciated
      proximity of the middle hepatic vein to the gallbladder bed.
AB  - Uncontrollable hemorrhage during laparoscopic cholecystectomy occurs in 0.1% to
      1.9% of all cases, with 88% originating from the gallbladder bed. The anatomical
      proximity between major branches of the middle hepatic vein and the gallbladder
      bed, and hence the risk of intraoperative bleeding, is unclear. CT scans of 20
      random patients were retrospectively reviewed to identify the closest distance
      between branches of the middle hepatic vein and the gallbladder bed. The vein
      diameter was also recorded. Risk factors for intraoperative bleeding during
      laparoscopic cholecystectomy were also retrospectively reviewed. Large branches
      (mean diameter = 2.1 mm) of the middle hepatic vein are directly adjacent to the
      gallbladder bed in 10% of patients. An additional 10% of cases also possess
      branches within 1 mm of the gallbladder bed. Chronically scarred and contracted
      gallbladder disease may increase the risk of significant bleeding, requiring
      conversion. Twenty percent of all cases will display a large branch of the middle
      hepatic vein adherent or immediately adjacent to the gallbladder fossa. These
      patients are at increased risk for intraoperative bleeding. Furthermore,
      contracted gallbladders with evidence of chronic disease may be at increased risk
      for significant hemorrhage.

PMID- 16966036
TI  - Retroperitoneal paraganglioma: single-institution experience and review of the
      literature.
AB  - Paragangliomas are rare tumors arising from extra-adrenal chromaffin cells. We
      examined the clinical characteristics of all patients at our institution having
      paragangliomas resected from 1984 through 2005. Of 253 resections, 22 (9%) were
      retroperitoneal and were selected for further study. The ratio of males to
      females was 1.3:1, and the median age was 39 years. The average size, rate of
      metastasis (i.e., malignancy), and rate of function was 7.4 cm, 9.5%, and 57.1%,
      respectively. Tumors larger than 7 cm were more likely to require adjacent organ
      resection (P = 0.01). The overall 5-year survival was 73%. Survival was
      significantly worse after metastasis (P = 0.0023) but did not depend on the tumor
      diameter, the secreting function of the tumor, the status of surgical margins of
      resection, or status of the resected lymph nodes.

PMID- 16966037
TI  - Bile duct growing factor: an alternate technique for reconstruction of thin bile
      ducts after iatrogenic injury.
AB  - A variant of bilioenteric anastomosis, laterolateral hepatojejunostomy, is
      described in which the opened anterior aspect of the common hepatic duct and left
      hepatic duct is anastomosed to a Roux jejunal limb. This technique is specially
      designed for thin, injured bile ducts in which a conventional anastomosis is
      difficult due to the small diameter of the ducts. A wide anastomosis is obtained,
      leaving the posterior wall as a conduit for bile, ensuring an adequate
      anastomotic diameter.

PMID- 16966038
TI  - Biliary pancreatitis.

PMID- 16966039
TI  - Transverse colon herniation through the foramen of Winslow presenting with
      unusual CT findings.
AB  - Bowel herniation through the foramen of Winslow is among the rarest of internal
      hernias, accounting for less than 0.8%. In its origin, a pivotal role is played
      by some anatomic variations, or anomalies such as the increased mobility of the
      right transverse colon, and maybe the exceedingly large bore of the foramen
      itself. The first case of hernia through the foramen of Winslow was reported by
      Blandin in 1834. Since then, no more that 200 new cases have been described.
      Diagnosis usually is established during surgery while treating a bowel
      obstruction. Only in an exceedingly small group of patients is diagnosis achieved
      preoperatively on the basis of radiological findings. We describe a
      preoperatively diagnosed case of transverse colon herniation through the foramen
      of Winslow, showing a portal vein narrowing and periportal lymphedema at computed
      tomography (CT). To the best of our knowledge, only a few cases of preoperative
      CT diagnosis of Winslow foramen hernia have been described in the past. None had
      the above-mentioned CT findings.

PMID- 16966040
TI  - Cost-saving effect of treatment algorithm for chronic anal fissure: a prospective
      analysis.

PMID- 16966043
TI  - Laparoscopic liver resections: extent of resection defines length of stay.

PMID- 16966044
TI  - More on: what's in a name, of and around the pancreas?

PMID- 16966045
TI  - Management of pain in small duct chronic pancreatitis.

PMID- 16966048
TI  - Predicting iron-fortified soy sauce consumption intention: application of the
      theory of planned behavior and health belief model.
AB  - OBJECTIVE: To identify variables that significantly predict the intention of iron
      ethylenediaminetetraacetic acid (NaFeEDTA)-fortified soy sauce (FeSS)
      consumption. DESIGN: A cross-sectional questionnaire survey, based on the Theory
      of Planned Behavior (TPB) and Health Belief Model (HBM), was administered, and a
      multistage, stratified sampling method was carried out to select study samples.
      SETTING: Urban and rural areas in Guizhou province, China. SUBJECTS: 636 women
      from rural areas and 454 from urban areas completed 1090 eligible questionnaires.
      VARIABLES MEASURED: Women's knowledge of FeSS; perceived severity and
      susceptibility of iron deficiency (ID) or iron deficiency anemia (IDA); and
      attitudes toward behavior, control beliefs, barriers, cues, intention to buy
      FeSS, health value, and health behavior identity factors were measured. ANALYSIS:
      A path analysis was conducted to test the goodness of fit of the model and to
      modify the model. Scale and factor analyses were conducted to verify the scale's
      reliability and construct validity. The alpha level was set at .05. RESULTS: The
      model explained 35% to 55% of the variance of behavioral intention. FeSS
      knowledge directly and indirectly affected the intention to buy FeSS. The
      behavioral intention was also impacted by women's health value and perception of
      perceived susceptibility and severity of IDA through the behavior identity and
      attitudes toward behavior. Cues, as an external factor, greatly affected the
      intention. The external control belief was a weak factor affecting intention.
      IMPLICATIONS FOR RESEARCH AND PRACTICE: Integrated TPB and HBM explained the
      behavioral intention of FeSS consumption among women in Guizhou, China. Nutrition
      education should emphasize behavioral attitudes and identity, and improve
      knowledge of FeSS and perception of ID and IDA, which would relieve anxiety about
      FeSS.

PMID- 16966049
TI  - Development and evaluation of the nutrition component of the Rapid Eating and
      Activity Assessment for Patients (REAP): a new tool for primary care providers.
AB  - OBJECTIVES: 1. To describe the development of a dietary assessment tool (Rapid
      Eating and Activity Assessment for Patients [REAP]) that quickly assesses a
      patient's diet and physical activity and facilitates brief counselling by a
      primary care provider, and 2. To describe the evaluation of the REAP in terms of
      its reliability, validity, and ease of use by primary care providers. DESIGN,
      SETTING AND PARTICIPANTS: The evaluation of REAP included: 1) an implementation
      feasibility study conducted with 61 medical students and practicing physicians in
      practice settings at various medical schools; 2) a calibration study with 44
      Brown University Medical School students; 3) cognitive assessment testing with 31
      consumers in Rhode Island; and 4) a reliability and calibration study of the
      revised tool with 94 consumers in Rhode Island and Massachusetts. RESULTS: The
      feasibility study revealed moderately high rankings on usefulness, ease,
      practicality, and helpfulness. The calibration studies demonstrated that REAP has
      excellent test-retest reliability (r = 0.86, P < .0001), is correlated with the
      Healthy Eating Index score (r = 0.49, P = .0007), and is significantly associated
      with intake of most nutrients studied. CONCLUSIONS AND IMPLICATIONS: REAP has
      adequate reliability and validity to be used in primary care practices for
      nutrition assessment and counselling, and is also user-friendly for providers.

PMID- 16966050
TI  - The reach of a computer-tailored nutrition education program in the Dutch heart
      health community intervention "Hartslag Limburg".
AB  - OBJECTIVE: To study the reach of an efficacious, computer-tailored nutrition
      education tool in a field setting. DESIGN: Data from self-administered
      questionnaires were used. SETTING: The computer-tailored nutrition education tool
      (CTT) was adopted by a regional public health service organization and
      implemented in a regional heart-health community project. PARTICIPANTS: The 1293
      inhabitants of the region that requested the computer nutrition education tool
      during a 25-month implementation period. MAIN OUTCOME MEASURES: Demographic
      characteristics; intake of fat, fruit, and vegetables; and psychosocial
      behavioral determinants. ANALYSIS: Descriptive statistics. RESULTS: The CTT
      reached almost 1% of the targeted population. Most participants were female
      (82%), and almost half were low educated. Many participants had diets higher in
      fat and lower in fruits and vegetables than recommended, were unaware of their
      unfavorable diets, and had low self-efficacy and intentions towards change.
      CONCLUSIONS AND IMPLICATIONS: Only a small, but possibly important, part of the
      target population was reached. Additional ways to reach more people should be
      explored.

PMID- 16966051
TI  - Intergenerational family conversations and decision making about eating
      healthfully.
AB  - OBJECTIVE: To explore how youth, parents, and grandparents discuss issues related
      to eating healthfully and unhealthfully and to identify intergenerational
      strategies for educators to improve this communication. DESIGN: In three
      intergenerational focus groups, each with 4-8 families, a trained moderator asked
      questions about family practices and conversations for eating healthfully and
      unhealthfully. SETTING: Three focus group sites, each with Pennsylvania Nutrition
      Education Program sites (PANEP) programs serving low-income populations and
      multigenerational clientele, based in geographically and culturally diverse
      communities in Pennsylvania. PARTICIPANTS: Forty-four individuals (21 pre-teens,
      16 parents, and 7 grandparents) from 17 families. PHENOMENON OF INTEREST: How
      youth, parents, and grandparents discuss and influence each other's healthful and
      unhealthful eating practices. ANALYSIS: "Strength" of evidence determined by
      repetition of ideas across focus groups and from the respondents' quotes
      providing in-depth information. RESULTS: Families demonstrated a wide range of
      ways that family communication is associated with the adoption of healthful and
      unhealthful patterns of eating. Parents and grandparents expressed anguish over
      their struggle and inability to help their children eat more healthfully. All
      three generations enumerated strategies for dealing with disagreement.
      CONCLUSIONS AND IMPLICATIONS: Grandparents, parents and children indicate that
      they need opportunities to learn together and communicate about ways to improve
      nutrition behaviors.

PMID- 16966052
TI  - Low-income American Indians' perceptions of diabetes.
AB  - OBJECTIVE: To determine inner city American Indians' perceptions of diabetes;
      find out how they manage their disease; and identify what health care
      improvements may be necessary for this population. DESIGN: Eight focus group
      discussions conducted with diabetic inner city American Indian adults. SETTING:
      Focus group discussions led by moderator using open-ended questions with prompts.
      PARTICIPANTS: Eligibility criteria include age (> or = 18 years), a self-reported
      diagnosis of diabetes, and self-identification as inner city American Indian.
      Participants were screened by telephone to ensure all criteria were met. Forty
      inner city American Indian men and women participated in 8 focus groups.
      PHENOMENON OF INTEREST: American Indians' perception of diabetes, its treatment,
      and how they manage the disease. ANALYSIS: Focus group discussions were tape
      recorded and transcribed verbatim. Transcripts were analyzed by coding responses
      and identifying common themes according to content analysis procedures.
      Quantitative data from self-administered demographic forms were analyzed.
      RESULTS: Participants could verbalize information regarding treatment and
      management of diabetes, but few could apply this information to their own lives.
      Some participants were homeless or without insurance, which makes successful
      disease management difficult. Perceptions of the health care system varied; a
      majority felt the system was meeting their needs, whereas others said it was not
      adequate. IMPLICATIONS FOR RESEARCH AND PRACTICE: The study identified the need
      for health care workers to develop a better understanding of how this population
      lives; doing so could improve patient compliance to treatment. The results may
      provide direction for the development of culturally specific diabetes education
      appropriate for low-income patients focusing on the diabetic diet and exercise,
      and suggesting ways that the patient can move from knowing the information to
      implementing behavior change.

PMID- 16966053
TI  - Use of pictures to facilitate nutrition education for low-income African American
      women.

PMID- 16966054
TI  - Hispanic/Latino health issues seminars: a holistic approach to increasing
      cultural competency among health care professionals.

PMID- 16966055
TI  - Cooking Up Fun! A youth development strategy that promotes independent food
      skills.

PMID- 16966056
TI  - Cooking with a Chef: an innovative program to improve mealtime practices and
      eating behaviors of caregivers of preschool children.

PMID- 16966057
TI  - Digital photo receivers are a viable technology for nutrition education of low
      income persons.

PMID- 16966058
TI  - Wisconsin's Current Concepts in Nutrition and Aging annual conference provides
      current, reliable, and usable information for nutrition professionals.

PMID- 16966061
TI  - [New diagnostic tools in renal transplantation].
AB  - Renal transplantation is the best treatment available for end stage renal
      disease. The determination of human genome has profoundly modified the possible
      approaches of renal transplant recipient by allowing tailoring of
      immunosuppressive drugs and immunologic diagnosis. The aim of this review article
      is to determine the role of these various techniques during the different step
      before and after transplantation. Genotyping, transcriptome analysis, proteomic
      as well as the specific immune response are analyzed in this article.

PMID- 16966062
TI  - [Transfusion-transmitted virus (TTV) and renal failure].
AB  - In 1997, a new DNA virus, designated TTV "Transfusion Transmitted Virus", was
      isolated and seemed to be associated with non A-G post-transfusion hepatitis. The
      virus infects mainly patients at risk for parenteral exposure and hence, prone to
      develop chronic liver disease, as well as healthy populations worldwide. Few
      reports, however, have been published on the epidemiology and potential
      significance of TTV infection in patients with renal disease. This paper reviews,
      characterization of the virus, the history of its discovery, taxonomy and
      identification. Current status of TTV infection in patients with renal diseases
      are also summarised.

PMID- 16966063
TI  - [Nephrotoxicity of sirolimus: experimental and clinical data].
AB  - Sirolimus (SRL, rapamycin) is a potent immunosuppressive drug that binds to and
      inhibits mammalian Target Of Rapamycine (mTOR) kinase activity, a central
      controller of cell growth. In response to amino acids, hormones and growth
      factors, mTOR activates the translational machinery. By inhibiting mTOR, SRL
      reduces the translational process and T-cell proliferation in the mid-to-late G1
      phase of the cell cycle. The antiproliferative effects of SRL are not limited to
      activated T cells. SRL has also been shown to block the cell cycle in various
      cell types such as epithelial renal cells, and many types of tumor cell lines.
      Since the approval by the US Food and Drug Administration and by the European
      agency, SRL has provoked great interest, as evidenced by the exponential increase
      in clinical studies. However, whereas preclinical studies failed to show any
      nephrotoxic effect on animal models, many clinical trials raised the possibility
      that SRL might be associated with renal adverse events. The evidence for SRL
      associated early graft nephrotoxicity emerged from these results, and subsequent
      experimental data gave some explanations about the involved mechanisms. The aim
      of this review is to summarize the various renal adverse events reported in
      clinical studies and to present the experimental evidence for putative mechanisms
      of action for this SRL-induced nephrotoxicity.

PMID- 16966064
TI  - [Darbepoetin-alfa treatment of anemia secondary to chronic renal failure in
      dialysis patients: Results of a French multicenter study].
AB  - Darbepoetin alfa is a unique genetically engineered glycoprotein with a three
      fold longer terminal half-life than recombinant human erythropoietin (rHuEPO).
      The objective of this study was to determine if darbepoetin alfa administered at
      a reduced dosing frequency relative to the prior rHuEpo regimen is an effective
      and safe alternative for treating renal anemia in patients undergoing dialysis. A
      total of 1,008 French hemodialysis and peritoneal dialysis patients receiving
      stable rHuEPO therapy by either the intravenous (i.v., N = 217) or subcutaneous
      (s.c., N = 791) route were switched to darbepoetin alfa given by the same route
      of administration at a reduced dosing frequency. Patients receiving rHuEPO once
      weekly (N = 248, 25%) were switched to darbepoetin alfa every two weeks, and
      those receiving rHuEPO two or three times weekly (N = 760, 75%) were switched to
      darbepoetin alfa once weekly. The doses of darbepoetin alfa were titrated to
      maintain hemoglobin concentration in the target range of 10.0 to 13.0 g/dl for up
      to 24 weeks. The primary endpoint was the change in hemoglobin between baseline
      and the evaluation period (weeks 21-24). Adjusted (for covariates that might
      influence hemoglobin response) mean change in hemoglobin from baseline to the
      evaluation period was not clinically significant: +0.11 g/dl (95% CI: -0.30;
      0.52). An i.v./s.c. dose ratio of 0.96 (95% CI: 0.86; 1.06) at evaluation
      confirms previous findings that darbepoetin alfa dose requirements were not
      different for the s.c. and i.v. routes. At the end of the evaluation period, more
      than 98% of patients successfully maintained hemoglobin within the target range
      and at their darbepoetin alfa assigned dosing frequency. Darbepoetin alfa was
      well tolerated with a safety profile consistent with that observed in previous
      darbepoetin alfa studies. Darbepoetin alfa administered at a reduced dosing
      frequency relative to the prior rHuEpo regimen effectively maintains hemoglobin
      in the target range in dialysis patients with renal anemia.

PMID- 16966065
TI  - [Nephronophtisis].
AB  - Nephronophthisis is a chronic tubulo-interstitial nephritis which progress to
      terminal renal failure. It is an heterogeneous entity at the clinical as well as
      at the genetic level. There are three main clinical forms of nephronophtisis
      which have been associated with five gene defects. Juvenile nephronophtisis, the
      most frequent, progress to end stage renal failure before age 15. It is an
      autosomal recessive disease which is responsible for a urine concentration defect
      starting after age 2, failure to thrive and a progressive deterioration of renal
      function without signs of glomerular disease. Kidney size is normal. Histologic
      lesions concern tubular basement membranes which are thickened and multilayered
      or thinned. There is an associated interstitial fibrosis. Some children present
      with extrarenal symptoms: tapetoretinal degeneration (Senior-Loken syndrome),
      mental retardation, cerebellar ataxia, bone anomalies or liver involvement.
      Infantile nephronophtisis is a recessive autosomic tubulo-interstitial nephritis
      with cortical microcysts which progress to end stage renal failure before age 5.
      Adolescent nephronophtisis is a less frequent form of nephronophtisis. Medullary
      cystic disease is transmitted as an autosomic dominant trait. Clinical and
      histological signs are similar to nephronophthisis, but the disease progress
      later to terminal renal failure and is not accompanied by extra-renal symptoms.
      Several genes which are involved in nephronophtisis, encode proteins that
      localize in different cell compartments, in particular to the primary apical
      cilia, as it is the case for many other cystic kidney diseases.

PMID- 16966066
TI  - Comments and controversies: magnetic resonance spectroscopy and gliomas.
AB  - In vivo proton magnetic resonance spectroscopy (1HMRS) can substantially improve
      the non-invasive categorization of human brain tumors, especially for gliomas. It
      provides greater information concerning tumor activity and characterization of
      the tumor tissue than is possible with MRI techniques alone. Moreover, 1HMRS may
      ultimately prove to be a highly beneficial modality in the post-irradiation care
      of patients with brain gliomas. This paper reviews the current status of 1HMRS
      with the emphasis on its clinical utility in the diagnosis of active tumor
      processes of gliomas, and its use in planning surgical and radiation therapy
      interventions and monitoring tumor treatment paradigms.

PMID- 16966067
TI  - Volume definition in radiotherapy planning for lung cancer: how the radiologist
      can help.
AB  - Effective treatment for carcinoma of the lung remains one of the biggest
      challenges in oncology. Radical radiotherapy may be a curative option for
      patients who are unsuitable for radical surgery either because of disease stage
      or because of co-morbidity. Long-term disease control with radical radiotherapy
      is disappointing with only about 6% of patients treated being alive at 5 years.
      Technological advances involved in the planning and delivery of radiotherapy may
      improve this. The advent of conformal radiotherapy, utilizing computed tomography
      and three-dimensional planning systems, allows much more accurate shaping of the
      radiation fields. This greater accuracy of target volume definition facilitates a
      reduction in the radiation dose to normal tissues, allowing for dose escalation
      to the tumour. Delineation of the target volume can be problematic. Conventional
      CT has limitations in term of distinguishing between benign and malignant
      tissues, e.g. the size criteria for involved lymph nodes. The oncologist uses a
      combination of radiological and clinical information when defining the target
      volume but their radiological interpretation of imaging is inferior to that of a
      radiologist. The Royal College of Radiologists (RCR) issued guidance in 2004 on
      the optimal imaging strategies for common cancers. These guidelines address
      issues regarding the localisation and staging of cancers and treatment planning,
      and also reporting and training. They recommend the development of closer links
      between radiologists and oncologists to optimise the interpretation of imaging
      and target volume definition. This article aims to briefly explain the planning
      process involved in irradiating lung cancers, highlight problematic areas and
      suggest ways in which co-operation with radiologists may improve the delivery of
      radiotherapy and therefore the treatment outcomes for this group of patients.

PMID- 16966068
TI  - Imaging of testicular germ cell tumours.
AB  - In testicular germ cell tumour (GCT), imaging plays a central role in assessment
      of tumour bulk, sites of metastases, monitoring response to therapy, surgical
      planning and accurate assessment of disease at relapse. The primary modality used
      for imaging patients with GCT is computed tomography (CT) but plain film
      radiography, ultrasound, magnetic resonance imaging (MRI) and positron emission
      tomography (PET) may all have roles to play. This article reviews the role of
      imaging of testicular germ cell tumours.

PMID- 16966069
TI  - Image guided biopsy in the management of cancer of the ovary.
AB  - When used in the context of multidisciplinary team discussion, image guided
      biopsy using ultrasound (US) or computed tomography (CT) guidance is of value in
      planning management of women with suspected ovarian cancer and peritoneal
      carcinomatosis (PC) of uncertain aetiology. It is essential in women believed to
      have ovarian cancer but with poor performance status or with advanced disease
      believed beyond the scope of primary cytoreductive surgery for whom staging
      surgical pathology will not be obtained. It provides a site-specific primary
      tumour diagnosis in 93% of cases and it should replace diagnostic laparoscopy or
      laparotomy for this purpose. It allows provision of primary (neoadjuvant)
      chemotherapy based on a firm histological diagnosis. It is mandatory in women
      with a history of cancer whose metastases may mimic ovarian cancer (e.g. breast,
      GI tract, melanoma). More women with prior breast cancer who re-present with
      peritoneal cancer will have a new gynaecological primary than recurrence of their
      original primary tumour; the two options require radically different therapies.
      Finally it is a valuable problem solving tool in situations of diagnostic
      uncertainty, e.g. unusual imaging patterns of disease such as PC with bilateral
      solid ovarian masses or non-enlarged ovaries and with an unusual tumour marker
      profiles suggesting primary tumours outwith the ovary. The technique is simple,
      safe and effective and can be combined with palliative drainage of ascites at the
      same procedure.

PMID- 16966071
TI  - Testing needed for acesulfame potassium, an artificial sweetener.

PMID- 16966072
TI  - Chemical mixtures: greater-than-additive effects?

PMID- 16966073
TI  - Comparing risk of West Nile Virus against risk of adulticiding.

PMID- 16966074
TI  - WHO/ILSI affiliation sustained.

PMID- 16966075
TI  - RTP leaders unite to advance environmental health.

PMID- 16966076
TI  - Monitoring environmental exposures: now it's personal.

PMID- 16966077
TI  - The price of gold in Chile.

PMID- 16966078
TI  - T rays vs. terrorists: widening the security spectrum.

PMID- 16966080
TI  - Chemical plants remain vulnerable to terrorists: a call to action.
AB  - U.S. chemical plants currently have potentially catastrophic vulnerabilities as
      terrorist targets. The possible consequences of these vulnerabilities echo from
      the tragedies of the Bhopal incident in 1984 to the terrorist attacks on 11
      September 2001 and, most recently, Hurricanes Katrina and Rita. Findings from a
      2004 nationwide participatory research study of 125 local union leaders at sites
      with very large volumes of highly hazardous chemicals suggest that voluntary
      efforts to achieve chemical plant security are not succeeding. Study respondents
      reported that companies had only infrequently taken actions that are most
      effective in preventing or in preparing to respond to a terrorist threat. In
      addition, companies reportedly often failed to involve key stakeholders,
      including workers, local unions, and the surrounding communities, in these
      efforts. The environmental health community thus has an opportunity to play a key
      role in advocating for and supporting improvements in prevention of and
      preparation for terrorist attacks. Policy-level recommendations to redress
      chemical site vulnerabilities and the related ongoing threats to the nation's
      security are as follows: a) specify detailed requirements for chemical site
      assessment and security ; b) mandate audit inspections supported by significant
      penalties for cases of noncompliance ; c) require progress toward achieving
      inherently safer processes, including the minimizing of storage of highly
      hazardous chemicals ; d) examine and require additional effective actions in
      prevention, emergency preparedness, and response and remediation ; e) mandate and
      fund the upgrading of emergency communication systems ; and f) involve workers
      and community members in plan creation and equip and prepare them to prevent and
      respond effectively to an incident.

PMID- 16966081
TI  - The chernobyl accident 20 years on: an assessment of the health consequences and
      the international response.
AB  - BACKGROUND: The Chernobyl accident in 1986 caused widespread radioactive
      contamination and enormous concern. Twenty years later, the World Health
      Organization and the International Atomic Energy Authority issued a generally
      reassuring statement about the consequences. Accurate assessment of the
      consequences is important to the current debate on nuclear power. OBJECTIVES: Our
      objectives in this study were to evaluate the health impact of the Chernobyl
      accident, assess the international response to the accident, and consider how to
      improve responses to future accidents. DISCUSSION: So far, radiation to the
      thyroid from radioisotopes of iodine has caused several thousand cases of thyroid
      cancer but very few deaths ; exposed children were most susceptible. The focus on
      thyroid cancer has diverted attention from possible nonthyroid effects, such as
      mini-satellite instability, which is potentially important. The international
      response to the accident was inadequate and uncoordinated, and has been
      unjustifiably reassuring. Accurate assessment of Chernobyl's future health
      effects is not currently possible in the light of dose uncertainties, current
      debates over radiation actions, and the lessons from the late consequences of
      atomic bomb exposure. CONCLUSIONS: Because of the uncertainties over the dose
      from and the consequences of the Chernobyl accident, it is essential that
      investigations of its effects should be broadened and supported for the long
      term. Because of the problems with the international response to Chernobyl, the
      United Nations should initiate an independent review of the actions and
      assignments of the agencies concerned, with recommendations for dealing with
      future international-scale accidents. These should involve independent scientists
      and ensure cooperation rather than rivalry.

PMID- 16966082
TI  - Climate change and human health impacts in the United States: an update on the
      results of the U.S. national assessment.
AB  - The health sector component of the first U.S. National Assessment, published in
      2000, synthesized the anticipated health impacts of climate variability and
      change for five categories of health outcomes: impacts attributable to
      temperature, extreme weather events (e.g., storms and floods) , air pollution,
      water- and food-borne diseases, and vector- and rodent-borne diseases. The Health
      Sector Assessment (HSA) concluded that climate variability and change are likely
      to increase morbidity and mortality risks for several climate-sensitive health
      outcomes, with the net impact uncertain. The objective of this study was to
      update the first HSA based on recent publications that address the potential
      impacts of climate variability and change in the United States for the five
      health outcome categories. The literature published since the first HSA supports
      the initial conclusions, with new data refining quantitative exposure-response
      relationships for several health end points, particularly for extreme heat events
      and air pollution. The United States continues to have a very high capacity to
      plan for and respond to climate change, although relatively little progress has
      been noted in the literature on implementing adaptive strategies and measures.
      Large knowledge gaps remain, resulting in a substantial need for additional
      research to improve our understanding of how weather and climate, both directly
      and indirectly, can influence human health. Filling these knowledge gaps will
      help better define the potential health impacts of climate change and identify
      specific public health adaptations to increase resilience.

PMID- 16966083
TI  - Effects of airway exposure to nanoparticles on lung inflammation induced by
      bacterial endotoxin in mice.
AB  - BACKGROUND: Although adverse health effects of particulate matter with a diameter
      of < 100 nm (nanoparticles) have been proposed, molecular and/or experimental
      evidence for their facilitation of lung inflammation in vivo is not fully
      defined. OBJECTIVE: In the present study we investigated the effects of
      nanoparticles on lung inflammation related to bacterial endotoxin
      [lipopolysaccharide (LPS) ] in mice. RESULTS: We intratracheally administered
      vehicle, two sizes (14 nm, 56 nm) of carbon black nanoparticles (4 mg/kg) , LPS
      (2.5 mg/kg) , or LPS plus nanoparticles and evaluated parameters for lung
      inflammation and coagulation. Nanoparticles alone induced slight lung
      inflammation and significant pulmonary edema compared with vehicle. Fourteen
      nanometer nanoparticles intensively aggravated LPS-elicited lung inflammation and
      pulmonary edema that was concomitant with the enhanced lung expression of
      interleukin-1beta (IL-1beta) , macrophage inflammatory protein-1alpha (MIP
      1alpha) , macrophage chemoattractant protein-1, MIP-2, and keratinocyte
      chemoattractant in overall trend, whereas 56-nm nanoparticles did not show
      apparent effects. Immunoreactivity for 8-hydroxyguanosine, a marker for oxidative
      stress, was more intense in the lungs from the LPS + 14-nm nanoparticle group
      than in those from the LPS group. Circulatory fibrinogen levels were higher in
      the LPS + plus 14-nm nanoparticle group than in the LPS group. CONCLUSIONS: Taken
      together, evidence indicates that nanoparticles can aggravate lung inflammation
      related to bacterial endotoxin, which is more prominent with smaller particles.
      The enhancement may be mediated, at least partly, via the increased local
      expression of proinflammatory cytokines and via the oxidative stress.
      Furthermore, nanoparticles can promote coagulatory disturbance accompanied by
      lung inflammation.

PMID- 16966084
TI  - Extreme temperatures and mortality: assessing effect modification by personal
      characteristics and specific cause of death in a multi-city case-only analysis.
AB  - BACKGROUND: Extremes of temperature are associated with short-term increases in
      daily mortality. OBJECTIVES: We set out to identify subpopulations and mortality
      causes with increased susceptibility to temperature extremes. METHODS: We
      conducted a case-only analysis using daily mortality and hourly weather data from
      50 U.S. cities for the period 1989-2000, covering a total of 7,789,655 deaths. We
      used distributions of daily minimum and maximum temperature in each city to
      define extremely hot days (>/= 99 th percentile) and extremely cold days (</= 1st
      percentile) , respectively. For each (hypothesized) effect modifier, a city
      specific logistic regression model was fitted and an overall estimate calculated
      in a subsequent meta-analysis. RESULTS: Older subjects [odds ratio (OR) = 1.020 ;
      95% confidence interval (CI) , 1.005-1.034], diabetics (OR = 1.035 ; 95% CI,
      1.010-1.062) , blacks (OR = 1.037 ; 95% CI, 1.016-1.059) , and those dying
      outside a hospital (OR = 1.066 ; 95% CI, 1.036-1.098) were more susceptible to
      extreme heat, with some differences observed between those dying from a
      cardiovascular disease and other decedents. Cardiovascular deaths (OR = 1.053 ;
      95% CI, 1.036-1.070) , and especially cardiac arrest deaths (OR = 1.137 ; 95% CI,
      1.051-1.230) , showed a greater relative increase on extremely cold days, whereas
      the increase in heat-related mortality was marginally higher for those with
      coexisting atrial fibrillation (OR = 1.059 ; 95% CI, 0.996-1.125) . CONCLUSIONS:
      In this study we identified several subpopulations and mortality causes
      particularly susceptible to temperature extremes. This knowledge may contribute
      to establishing health programs that would better protect the vulnerable.

PMID- 16966085
TI  - Gene expression changes related to endocrine function and decline in reproduction
      in fathead minnow (Pimephales promelas) after dietary methylmercury exposure.
AB  - BACKGROUND: Methylmercury (MeHg) is a known neurotoxic agent, but the mechanisms
      by which MeHg may act on reproductive pathways are relatively unknown. Several
      studies have indicated potential changes in hormone levels as well as declines in
      vertebrates with increasing dietary MeHg exposure. OBJECTIVES: The purpose of
      this study was to identify alterations in gene expression associated with MeHg
      exposure, specifically those associated with previously observed changes in
      reproduction and reproductive biomarkers. Fathead minnows, Pimephales promelas,
      were fed one of three diets that were similar to documented concentrations of
      MeHg in the diets of wild invertivorous and piscivorous fish. We used a
      commercial macroarray in conjunction with quantitative polymerase chain reaction
      to examine gene expression in fish in relation to exposure to these
      environmentally relevant doses of MeHg. RESULTS: Expression of genes commonly
      associated with endocrine disruption was altered with Hg exposure. Specifically,
      we observed a marked up-regulation in vitellogenin mRNA in individual Hg-exposed
      males and a significant decline in vitellogenin gene expression in female fish
      with increasing Hg concentrations. Other genes identified by the macroarray
      experiment included those associated with egg fertilization and development,
      sugar metabolism, apoptosis, and electron transport. We also observed differences
      in expression patterns between male and female fish not related to genes
      specifically associated with reproduction, indicating a potential physiological
      difference in the reaction of males and females to MeHg. CONCLUSION: Gene
      expression data may provide insight into the mechanisms by which MeHg affects
      reproduction in fish and indicate how MeHg differs in its effect from other heavy
      metals and endocrine-disrupting compounds.

PMID- 16966086
TI  - The relation between temperature, ozone, and mortality in nine French cities
      during the heat wave of 2003.
AB  - BACKGROUND: During August 2003, record high temperatures were observed across
      Europe, and France was the country most affected. During this period, elevated
      ozone concentrations were measured all over the country. Questions were raised
      concerning the contribution of O3 to the health impact of the summer 2003 heat
      wave. METHODS: We used a time-series design to analyze short-term effects of
      temperature and O3 pollution on mortality. Counts of deaths were regressed on
      temperatures and O3 levels, controlling for possible confounders: long-term
      trends, season, influenza outbreaks, day of the week, and bank holiday effects.
      For comparison with previous results of the nine cities, we calculated pooled
      excess risk using a random effect approach and an empirical Bayes approach.
      FINDINGS: For the nine cities, the excess risk of death is significant (1.01% ;
      95% confidence interval, 0.58-1.44) for an increase of 10 microg/m3 in O3 level.
      For the 3-17 August 2003 period, the excess risk of deaths linked to O3 and
      temperatures together ranged from 10.6% in Le Havre to 174.7% in Paris. When we
      compared the relative contributions of O3 and temperature to this joint excess
      risk, the contribution of O3 varied according to the city, ranging from 2.5% in
      Bordeaux to 85.3% in Toulouse. INTERPRETATION: We observed heterogeneity among
      the nine cities not only for the joint effect of O3 and temperatures, but also
      for the relative contribution of each factor. These results confirmed that in
      urban areas O3 levels have a non-negligible impact in terms of public health.

PMID- 16966087
TI  - Reproductive hormone levels in men exposed to persistent organohalogen
      pollutants: a study of inuit and three European cohorts.
AB  - OBJECTIVE: Persistent organohalogen pollutant (POP) exposure may have a negative
      impact on reproductive function. The objective of this study was to assess the
      impact of POP exposure on the male hypothalamo-pituitary-gonadal axis.
      PARTICIPANTS: Participants included 184 Swedish fishermen and spouses of pregnant
      women from Greenland (n = 258), Warsaw, Poland (n = 113) , and Kharkiv, Ukraine
      (n = 194). EVALUATIONS/MEASUREMENTS: Serum levels of 2,2,4,4,5,5
      hexachlorobiphenyl (CB-153) and dichlorodiphenyl dichloroethene (p,p -DDE) were
      determined in the four populations, showing different exposure patterns: Swedish
      fishermen, high CB-153/low p,p -DDE; Greenland, high CB-153/high p,p -DDE;
      Warsaw, low CB-153/moderate p,p -DDE; Kharkiv, low CB-153/high p,p -DDE. Serum
      was also analyzed for testosterone, estradiol, sex hormone-binding globulin
      (SHBG) , inhibin B, luteinizing hormone (LH) , and follicle-stimulating hormone
      (FSH) . Free testosterone levels were calculated based on testosterone and SHBG.
      RESULTS: We found significant center-to-center variations in the associations
      between exposure and the outcomes. The most pronounced effects were observed in
      Kharkiv, where statistically significant positive associations were found between
      the levels of both CB-153 and p,p -DDE and SHBG, as well as LH. In Greenland,
      there was a positive association between CB-153 exposure and LH. In the pooled
      data set from all four centers, there was positive association between p,p -DDE
      and FSH levels [beta = 1.1 IU/L; 95% confidence interval (CI), 1.0-1.1 IU/L]. The
      association between CB-153 levels and SHBG was of borderline statistical
      significance (beta = 0.90 nmol/L; 95% CI, -0.04 to 1.9 nmol/L). CONCLUSIONS:
      Gonadotropin levels and SHBG seem to be affected by POP exposure, but the pattern
      of endocrine response is the subject of considerable geographic variation.

PMID- 16966089
TI  - Lung cancer attributable to indoor radon exposure in france: impact of the risk
      models and uncertainty analysis.
AB  - OBJECTIVE: The inhalation of radon, a well-established human carcinogen, is the
      principal-and omnipresent-source of radioactivity exposure for the general
      population of most countries. Scientists have thus sought to assess the lung
      cancer risk associated with indoor radon. Our aim here is to assess this risk in
      France, using all available epidemiologic results and performing an uncertainty
      analysis. METHODS: We examined the exposure-response relations derived from
      cohorts of miners and from joint analyses of residential case-control studies and
      considered the interaction between radon and tobacco. The exposure data come from
      measurement campaigns conducted since the beginning of the 1980s by the Institute
      for Radiation Protection and Nuclear Safety and the Directorate-General of Health
      in France. We quantified the uncertainties associated with risk coefficients and
      exposures and calculated their impact on risk estimates. RESULTS: The estimated
      number of lung cancer deaths attributable to indoor radon exposure ranges from
      543 [90% uncertainty interval (UI) , 75-1,097] to 3,108 (90% UI, 2,996-3,221) ,
      depending on the model considered. This calculation suggests that from 2.2% (90%
      UI, 0.3-4.4) to 12.4% (90% UI, 11.9-12.8) of these deaths in France may be
      attributable to indoor radon. DISCUSSION: In this original work we used different
      exposure-response relations from several epidemiologic studies and found that
      regardless of the relation chosen, the number of lung cancer deaths attributable
      to indoor radon appears relatively stable. Smokers can reduce their risk not only
      by reducing their indoor radon concentration but also by giving up smoking.

PMID- 16966088
TI  - The role of inflammatory mediators in the synergistic toxicity of ozone and 1
      nitronaphthalene in rat airways.
AB  - Ambient air is polluted with a mixture of pulmonary toxicants. Previous studies
      indicate that prior exposure to atmospheric oxidant pollutants such as ozone may
      significantly alter the response to other pollutants, such as 1-nitronaphthalene
      (1-NN) . 1-NN, a component of the particulate exhaust from diesel engines, has
      been found at low concentrations in ambient air. Using a metabolomic approach, we
      investigated inflammatory responses in arachidonic and linoleic acid biochemical
      cascades (35 metabolites) and the expression of 19 cytokines/chemokines at three
      time points (2, 6, and 24 hr) following exposure to 1-NN with and without prior
      long-term O3 exposure. Long-term O3 exposure is associated with biochemical
      changes that have been shown to render the lung resistant to further O3 exposure.
      This study indicates that airways of O3-tolerant rats exhibited a low level of
      chronic inflammation, rendering the lungs more susceptible to other environmental
      pollutants such as 1-NN. Specifically, a 12.5-mg/kg dose of 1-NN to O3-tolerant
      rats produced significantly higher levels of cysteinyl-leukotrienes in
      bronchiolar lavage fluid even when compared to a 50-mg/kg dose of 1-NN in rats
      exposed to filtered air. Collectively, these results indicate that the
      combination of exposures as encountered in polluted ambient air are considerably
      more injurious to the lung than would be anticipated from previous studies
      employing single exposures. The observed synergism between O3 and 1-NN may be
      causally related to a shift in a T-helper 1 to T-helper 2 immune response in the
      airways.

PMID- 16966090
TI  - Apoptosis and Bax expression are increased by coal dust in the polycyclic
      aromatic hydrocarbon-exposed lung.
AB  - BACKGROUND: Miners inhaling respirable coal dust (CD) frequently develop coal
      workers' pneumoconiosis, a dust-associated pneumoconiosis characterized by lung
      inflammation and variable fibrosis. Many coal miners are also exposed to
      polycyclic aromatic hydrocarbon (PAH) components of diesel engine exhaust and
      cigarette smoke, which may contribute to lung disease in these workers. Recently,
      apoptosis was reported to play a critical role in the development of another
      pneumoconiosis of miners, silicosis. In addition, CD was reported to suppress
      cytochrome P450 1A1 (CYP1A1) induction by PAHs. METHODS: We investigated the
      hypothesis that apoptosis plays a critical role in lung injury and down
      regulation of CYP1A1 induction in mixed exposures to CD and PAHs. We exposed rats
      intratracheally to 0.0, 2.5, 10.0, 20.0, or 40.0 mg/rat CD and, 11 days later, to
      intraperitoneal beta-naphthoflavone (BNF) , a PAH. In another group of rats
      exposed to CD and BNF, caspase activity was inhibited by injection of the pan
      caspase inhibitor Q-VD-OPH [quinoline-Val-Asp (OMe) -CH2-OPH]. RESULTS: In rats
      exposed to BNF, CD exposure increased alveolar expression of the proapoptotic
      mediator Bax but decreased CYP1A1 induction relative to BNF exposure alone. Pan
      caspase inhibition decreased CD-associated Bax expression and apoptosis but did
      not restore CYP1A1 activity. Further, CD-induced lung inflammation and alveolar
      epithelial cell hypertrophy and hyperplasia were not suppressed by caspase
      inhibition. CONCLUSIONS: Combined BNF and CD exposure increased Bax expression
      and apoptosis in the lung, but Bax and apoptosis were not the major determinants
      of early lung injury in this model.

PMID- 16966091
TI  - GIS approaches for the estimation of residential-level ambient PM concentrations.
AB  - Spatial estimations are increasingly used to estimate geocoded ambient
      particulate matter (PM) concentrations in epidemiologic studies because measures
      of daily PM concentrations are unavailable in most U.S. locations. This study was
      conducted to a) assess the feasibility of large-scale kriging estimations of
      daily residential-level ambient PM concentrations, b) perform and compare cross
      validations of different kriging models, c) contrast three popular kriging
      approaches, and d) calculate SE of the kriging estimations. We used PM data for
      PM with aerodynamic diameter </= 10 microm (PM10) and aerodynamic diameter </=
      2.5 microm (PM2.5) from the U.S. Environmental Protection Agency for the year
      2000. Kriging estimations were performed at 94,135 geocoded addresses of Women's
      Health Initiative study participants using the ArcView geographic information
      system. We developed a semiautomated program to enable large-scale daily kriging
      estimation and assessed validity of semivariogram models using prediction error
      (PE) , standardized prediction error (SPE) , root mean square standardized (RMSS)
      , and SE of the estimated PM. National- and regional-scale kriging performed
      satisfactorily, with the former slightly better. The average PE, SPE, and RMSS of
      daily PM10 semivariograms using regular ordinary kriging with a spherical model
      were 0.0629, -0.0011, and 1.255 microg/m3, respectively ; the average SE of the
      estimated residential-level PM10 was 27.36 microg/m3. The values for PM2.5 were
      0.049, 0.0085, 1.389, and 4.13 microg/m3, respectively. Lognormal ordinary
      kriging yielded a smaller average SE and effectively eliminated out-of-range
      predicted values compared to regular ordinary kriging. Semiautomated daily
      kriging estimations and semivariogram cross-validations are feasible on a
      national scale. Lognormal ordinary kriging with a spherical model is valid for
      estimating daily ambient PM at geocoded residential addresses.

PMID- 16966092
TI  - Airborne mold and endotoxin concentrations in New Orleans, Louisiana, after
      flooding, October through November 2005.
AB  - BACKGROUND: The hurricanes and flooding in New Orleans, Louisiana, in October and
      November 2005 resulted in damp conditions favorable to the dispersion of
      bioaerosols such as mold spores and endotoxin. OBJECTIVE: Our objective in this
      study was to assess potential human exposure to bioaerosols in New Orleans after
      the flooding of the city. METHODS: A team of investigators performed continuous
      airborne sampling for mold spores and endotoxin outdoors in flooded and
      nonflooded areas, and inside homes that had undergone various levels of
      remediation, for periods of 5-24 hr during the 2 months after the flooding.
      RESULTS: The estimated 24-hr mold concentrations ranged from 21,000 to 102,000
      spores/m3 in outdoor air and from 11,000 to 645,000 spores/m3 in indoor air. The
      mean outdoor spore concentration in flooded areas was roughly double the
      concentration in nonflooded areas (66,167 vs. 33,179 spores/m3 ; p < 0.05) . The
      highest concentrations were inside homes. The most common mold species were from
      the genera of Cladosporium and Aspergillus/Penicillium ; Stachybotrys was
      detected in some indoor samples. The airborne endotoxin concentrations ranged
      from 0.6 to 8.3 EU (endotoxin units) /m3 but did not vary with flooded status or
      between indoor and outdoor environments. CONCLUSIONS: The high concentration of
      mold measured indoors and outdoors in the New Orleans area is likely to be a
      significant respiratory hazard that should be monitored over time. Workers and
      returning residents should use appropriate personal protective equipment and
      exposure mitigation techniques to prevent respiratory morbidity and long-term
      health effects.

PMID- 16966093
TI  - Lung toxicity of ambient particulate matter from southeastern U.S. sites with
      different contributing sources: relationships between composition and effects.
AB  - BACKGROUND: Exposure to air pollution and, more specifically, particulate matter
      (PM) is associated with adverse health effects. However, the specific PM
      characteristics responsible for biological effects have not been defined.
      OBJECTIVES: In this project we examined the composition, sources, and relative
      toxicity of samples of PM with aerodynamic diameter </= 2.5 microm (PM2.5)
      collected from sites within the Southeastern Aerosol Research and
      Characterization (SEARCH) air monitoring network during two seasons. These sites
      represent four areas with differing sources of PM2.5, including local urban
      versus regional sources, urban areas with different contributions of
      transportation and industrial sources, and a site influenced by Gulf of Mexico
      weather patterns. METHODS: We collected samples from each site during the winter
      and summer of 2004 for toxicity testing and for chemical analysis and chemical
      mass balance-based source apportionment. We also collected PM2.5 downwind of a
      series of prescribed forest burns. We assessed the toxicity of the samples by
      instillation into rat lungs and assessed general toxicity, acute cytotoxicity,
      and inflammation. Statistical dose-response modeling techniques were used to rank
      the relative toxicity and compare the seasonal differences at each site.
      Projection-to-latent-surfaces (PLS) techniques examined the relationships among
      sources, chemical composition, and toxicologic end points. RESULTS AND
      CONCLUSIONS: Urban sites with high contributions from vehicles and industry were
      most toxic.

PMID- 16966094
TI  - Use of a physiologically based pharmacokinetic model for rats to study the
      influence of body fat mass and induction of CYP1A2 on the pharmacokinetics of
      TCDD.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly lipophilic chemical that
      distributes into adipose tissue, especially at low doses. However, at high doses
      TCDD sequesters in liver because it induces cytochrome P450 1A2 (CYP1A2) that
      binds TCDD. A physiologically based pharmacokinetic (PBPK) model was developed
      that included an inducible elimination rate of TCDD in the Sprague-Dawley rat.
      Objectives of this work were to characterize the influence of induction of CYP1A2
      and adipose tissue mass fraction on the terminal elimination half-life (t1/2) of
      TCDD using this PBPK model. When the model assumes a fixed elimination of TCDD,
      t1/2 increases with dose, due to hepatic sequestration. Because experimental data
      indicate that the t1/2 of TCDD decreases with dose, the model was modified to
      include an inducible elimination rate. The PBPK model was then used to compare
      the t1/2 after an increase of adipose tissue mass fraction from 6.9 to 70%. The
      model suggests that at low exposures, increasing adipose tissue mass increases
      the terminal t1/2. However, at higher exposures, as CYP1A2 is induced, the
      relationship between adipose tissue mass and t1/2 reaches a plateau. This
      demonstrates that an inducible elimination rate is needed in a PBPK model in
      order to describe the pharmacokinetics of TCDD. At low exposures these models are
      more sensitive to parameters related to partitioning into adipose tissue.

PMID- 16966095
TI  - Exit from arsenite-induced mitotic arrest is p53 dependent.
AB  - BACKGROUND: Arsenic is both a human carcinogen and a chemotherapeutic agent, but
      the mechanism of neither arsenic-induced carcinogenesis nor tumor selective
      cytotoxicity is clear. Using a model cell line in which p53 expression is
      regulated exogenously in a tetracycline-off system (TR9-7 cells) , our laboratory
      has shown that arsenite disrupts mitosis and that p53-deficient cells [p53(-)],
      in contrast to p53-expressing cells [p53(+)], display greater sensitivity to
      arsenite-induced mitotic arrest and apoptosis. OBJECTIVE: Our goal was to examine
      the role p53 plays in protecting cells from arsenite-induced mitotic arrest.
      METHODS: p53(+) and p53(-) cells were synchronized in G2 phase using Hoechst
      33342 and released from synchrony in the presence or absence of 5 microM sodium
      arsenite. RESULTS: Mitotic index analysis demonstrated that arsenite treatment
      delayed exit from G2 in p53(+) and p53(-) cells. Arsenite-treated p53(+) cells
      exited mitosis normally, whereas p53(-) cells exited mitosis with delayed
      kinetics. Microarray analysis performed on mRNAs of cells exposed to arsenite for
      0 and 3 hr after release from G2 phase synchrony showed that arsenite induced
      inhibitor of DNA binding-1 (ID1) differentially in p53(+) and p53(-) cells.
      Immunoblotting confirmed that ID1 induction was more extensive and sustained in
      p53(+) cells. CONCLUSIONS: p53 promotes mitotic exit and leads to more extensive
      ID1 induction by arsenite. ID1 is a dominant negative inhibitor of transcription
      that represses cell cycle regulatory genes and is elevated in many tumors. ID1
      may play a role in the survival of arsenite-treated p53(+) cells and contribute
      to arsenic carcinogenicity.

PMID- 16966096
TI  - Meeting report: development of environmental health indicators in Brazil and
      other countries in the americas.
AB  - This report summarizes the Brazilian experience on the design and implementation
      of environmental health, with contributions from Argentina, Canada, and Cuba,
      presented at the International Symposium on the Development of Indicators for
      Environmental Health Integrated Management, held in Recife, Pernambuco, Brazil,
      on 17-18 June 2004. The methodology for the development of environmental health
      indicators has been used as a reference in the implementation of environmental
      health surveillance in Brazil. This methodology has provided tools and processes
      to facilitate the understanding and to measure the determinants of risks to
      environmental health, to help decision makers control those risks. Key words:
      environmental health indicators, environmental health surveillance, integrated
      management.

PMID- 16966097
TI  - Experimental PVC material challenge in subjects with occupational PVC exposure.
AB  - BACKGROUND: Polyvinyl chloride (PVC) materials have been linked to asthma in
      several epidemiologic studies, but the possible causal factors remain unknown.
      PARTICIPANTS: We challenged 10 subjects experimentally to degraded PVC products
      under controlled conditions. All of the subjects had previously experienced
      respiratory symptoms suspected to be caused by this kind of exposure in their
      work place. Five subjects had doctor-diagnosed asthma. METHODS: The subjects were
      exposed to degraded PVC material in an exposure chamber ; a challenge with
      ceramic tile was used as the control test. We followed exhaled nitric oxide,
      nasal NO, lung functions, cytokines [tumor necrosis factor-alpha (TNF-alpha) ,
      interleukin-4 (IL-4) , IL-6, and IL-12] and NO in nasal lavage fluid (NAL) during
      and after the exposures. We also measured 2-ethylhexanol in exhaled breath
      samples and NAL. RESULTS: On the morning after the PVC exposure, subjects
      reported respiratory tract symptoms significantly more often than they did after
      the control test (50% vs. 0%, respectively ; p = 0.029 ; n = 10) . We did not
      detect any changes in lung functions or levels of exhaled NO, nasal NO, or NO in
      NAL after PVC challenge compared with the control test. Cytokine levels increased
      after both exposures, with no statistically significant difference between
      situations. All of the exhaled breath samples collected during the PVC exposure
      contained 2-ethylhexanol. CONCLUSIONS: PVC flooring challenge can evoke
      respiratory tract symptoms in exposed subjects. Our results do not support the
      hypothesis that PVC materials themselves evoke immediate asthmatic reactions. The
      chamber test used is well suited to this type of exposure study.

PMID- 16966098
TI  - Traffic-related air pollution and otitis media.
AB  - BACKGROUND: Otitis media is one of the most common infections in young children.
      Although exposure to environmental tobacco smoke is a known risk factor
      associated with otitis media, little information is available regarding the
      potential association with air pollution. OBJECTIVE: We set out to study the
      relationship between exposure to traffic-related air pollution and otitis media
      in two birth cohorts. METHODS: Individual estimates of outdoor concentrations of
      traffic-related air pollutants-nitrogen dioxide, fine particles [particulate
      matter with aerodynamic diameters </= 2.5 microm (PM2.5)], and elemental carbon
      were calculated for home addresses of approximately 3,700 and 650 infants from
      birth cohort studies in the Netherlands and Germany, respectively. Air pollution
      exposure was analyzed in relation to physician diagnosis of otitis media in the
      first 2 years of life. RESULTS: Odds ratios (adjusted for known major risk
      factors) for otitis media indicated positive associations with traffic-related
      air pollutants. An increase in 3 microg/m3 PM2.5, 0.5 microg/m3 elemental carbon,
      and 10 microg/m3 NO2 was associated with odds ratios of 1.13 (95% confidence
      interval, 1.00-1.27) , 1.10 (1.00-1.22) , and 1.14 (1.03-1.27) in the Netherlands
      and 1.24 (0.84-1.83) , 1.10 (0.86-1.41) , and 1.14 (0.87-1.49) in Germany,
      respectively. CONCLUSIONS: These findings indicate an association between
      exposure to traffic-related air pollutants and the incidence of otitis media.
      Given the ubiquitous nature of air pollution exposure and the importance of
      otitis media to children's health, these findings have significant public health
      implications.

PMID- 16966099
TI  - A longitudinal approach to assessing urban and suburban children's exposure to
      pyrethroid pesticides.
AB  - We conducted a longitudinal study to assess the exposure of 23 elementary school
      age children to pyrethroid pesticides, using urinary pyrethroid metabolites as
      exposure biomarkers. We substituted most of the children's conventional diets
      with organic food items for 5 consecutive days and collected two daily spot urine
      samples, first morning and before bedtime voids, throughout the 15-day study
      period. We analyzed urine samples for five common pyrethroid metabolites. We
      found an association between the parents' self-reported pyrethroid use in the
      residential environment and elevated pyrethroid metabolite levels found in their
      children's urine. Children were also exposed to pyrethroids through their
      conventional diets, although the magnitude was smaller than for the residential
      exposure. Children's ages appear to be significantly associated with pyrethroids
      exposure, which is likely attributed to the use of pyrethroids around the
      premises or in the facilities where older children engaged in the outdoor
      activities. We conclude that residential pesticide use represents the most
      important risk factor for children's exposure to pyrethroid insecticides. Because
      of the wide use of pyrethroids in the United States, the findings of this study
      are important for both children's pesticide exposure assessment and environmental
      public health.

PMID- 16966100
TI  - Exposure to phthalates in neonatal intensive care unit infants: urinary
      concentrations of monoesters and oxidative metabolites.
AB  - OBJECTIVE: We previously demonstrated that among 54 infants in neonatal intensive
      care units, exposure to polyvinyl chloride plastic medical devices containing the
      plasticizer di(2-ethylhexyl) phthalate (DEHP) is associated with urinary
      concentrations of mono(2-ethylhexyl) phthalate (MEHP) , a DEHP metabolite. In
      this follow-up report, we studied the neonates' exposure to DEHP-containing
      devices in relation to urinary concentrations of two other DEHP metabolites, and
      to urinary concentrations of metabolites of dibutyl phthalate (DBP) and
      benzylbutyl phthalate (BzBP) , phthalates found in construction materials and
      personal care products. MEASUREMENTS: A priori, we classified the intensiveness
      of these 54 infants' exposure to DEHP-containing medical products. We measured
      three metabolites of DEHP in infants' urine: MEHP and two of its oxidative
      metabolites, mono(2-ethyl-5-hydroxylhexyl) phthalate (MEHHP) and mono(2-ethyl-5
      oxohexyl) phthalate (MEOHP) . We also measured monobutyl phthalate (MBP) , a
      metabolite of DBP, and monobenzyl phthalate (MBzP), a metabolite of BzBP.
      RESULTS: Intensiveness of DEHP-containing product use was monotonically
      associated with all three DEHP metabolites. Urinary concentrations of MEHHP and
      MEOHP among infants in the high-DEHP-intensiveness group were 13-14 times the
      concentrations among infants in the low-intensiveness group (p</= 0.007).
      Concentrations of MBP were somewhat higher in the medium- and high-DEHP
      intensiveness group; MBzP did not vary by product use group. Incorporating all
      phthalate data into a structural equation model confirmed the specific monotonic
      association between intensiveness of product use and biologic measures of DEHP.
      CONCLUSION: Inclusion of the oxidative metabolites MEHHP and MEOHP strengthened
      the association between intensiveness of product use and biologic indices of DEHP
      exposure over that observed with MEHP alone.

PMID- 16966101
TI  - Lung radiology and pulmonary function of children chronically exposed to air
      pollution.
AB  - We analyzed the chest radiographs (CXRs) of 249 clinically healthy children, 230
      from southwest Mexico City and 19 from Tlaxcala. In contrast to children from
      Tlaxcala, children from southwest Mexico City were chronically exposed to ozone
      levels exceeding the U.S. National Ambient Air Quality Standards for an average
      of 4.7 hr/day and to concentrations of particulate matter (PM) with aerodynamic
      diameters </= 2.5 microm (PM2.5) above the annual standard. CXRs of Mexico City
      children demonstrated bilateral hyperinflation (151 of 230) and increased linear
      markings (121 of 230) . Hyperinflation and interstitial markings were
      significantly more common in Mexico City children (p < 0.0002 and 0.00006
      respectively) . Mexico City boys had a higher probability of developing
      interstitial markings with age (p = 0.004) . Computed tomography (CT) scans were
      obtained in 25 selected Mexico City children with abnormal CXRs. Mild bronchial
      wall thickening was seen in 10 of 25, prominent central airways in 4 of 25, air
      trapping in 8 of 21, and pulmonary nodules in 2 of 21. Only 7.8% of Mexico City
      children had abnormal lung function tests based on predicted values. These
      findings are consistent with bronchiolar, peribronchiolar, and/or alveolar duct
      inflammation, possibly caused by ozone, PM, and lipopolysaccharide exposure. The
      epidemiologic implications of these findings are important for children residing
      in polluted environments, because bronchiolar disease could lead to chronic
      pulmonary disease later in life.

PMID- 16966102
TI  - Autism spectrum disorders in relation to distribution of hazardous air pollutants
      in the san francisco bay area.
AB  - OBJECTIVE: To explore possible associations between autism spectrum disorders
      (ASD) and environmental exposures, we linked the California autism surveillance
      system to estimated hazardous air pollutant (HAP) concentrations compiled by the
      U.S. Environmental Protection Agency. METHODS: Subjects included 284 children
      with ASD and 657 controls, born in 1994 in the San Francisco Bay area. We
      assigned exposure level by census tract of birth residence for 19 chemicals we
      identified as potential neurotoxicants, developmental toxicants, and/or endocrine
      disruptors from the 1996 HAPs database. Because concentrations of many of these
      were highly correlated, we combined the chemicals into mechanistic and structural
      groups, calculating summary index scores. We calculated ASD risk in the upper
      quartiles of these group scores or individual chemical concentrations compared
      with below the median, adjusting for demographic factors. RESULTS: The adjusted
      odds ratios (AORs) were elevated by 50% in the top quartile of chlorinated
      solvents and heavy metals [95% confidence intervals (CIs) , 1.1-2.1], but not for
      aromatic solvents. Adjusting for these three groups simultaneously led to
      decreased risks for the solvents and increased risk for metals (AORs for metals:
      fourth quartile = 1.7 ; 95% CI, 1.0-3.0 ; third quartile = 1.95 ; 95% CI, 1.2
      3.1) . The individual compounds that contributed most to these associations
      included mercury, cadmium, nickel, trichloroethylene, and vinyl chloride.
      CONCLUSIONS: Our results suggest a potential association between autism and
      estimated metal concentrations, and possibly solvents, in ambient air around the
      birth residence, requiring confirmation and more refined exposure assessment in
      future studies.

PMID- 16966103
TI  - Key scientific issues in the health risk assessment of trichloroethylene.
AB  - Trichloroethylene (TCE) is a common environmental contaminant at hazardous waste
      sites and in ambient and indoor air. Assessing the human health risks of TCE is
      challenging because of its inherently complex metabolism and toxicity and the
      widely varying perspectives on a number of critical scientific issues. Because of
      this complexity, the U.S. Environmental Protection Agency (EPA) drew upon
      scientific input and expertise from a wide range of groups and individuals in
      developing its 2001 draft health risk assessment of TCE. This scientific
      outreach, which was aimed at engaging a diversity of perspectives rather than
      developing consensus, culminated in 2000 with 16 state-of-the-science articles
      published together as an Environmental Health Perspectives supplement. Since that
      time, a substantial amount of new scientific research has been published that is
      relevant to assessing TCE health risks. Moreover, a number of difficult or
      controversial scientific issues remain unresolved and are the subject of a
      scientific consultation with the National Academy of Sciences coordinated by the
      White House Office of Science and Technology Policy and co-sponsored by a number
      of federal agencies, including the U.S. EPA. The articles included in this mini
      monograph provide a scientific update on the most prominent of these issues: the
      pharmacokinetics of TCE and its metabolites, mode(s) of action and effects of TCE
      metabolites, the role of peroxisome proliferator-activated receptor in TCE
      toxicity, and TCE cancer epidemiology.

PMID- 16966104
TI  - Issues in the pharmacokinetics of trichloroethylene and its metabolites.
AB  - Much progress has been made in understanding the complex pharmacokinetics of
      trichloroethylene (TCE) . Qualitatively, it is clear that TCE is metabolized to
      multiple metabolites either locally or into systemic circulation. Many of these
      metabolites are thought to have toxicologic importance. In addition, efforts to
      develop physiologically based pharmacokinetic (PBPK) models have led to a better
      quantitative assessment of the dosimetry of TCE and several of its metabolites.
      As part of a mini-monograph on key issues in the health risk assessment of TCE,
      this article is a review of a number of the current scientific issues in TCE
      pharmacokinetics and recent PBPK modeling efforts with a focus on literature
      published since 2000. Particular attention is paid to factors affecting PBPK
      modeling for application to risk assessment. Recent TCE PBPK modeling efforts,
      coupled with methodologic advances in characterizing uncertainty and variability,
      suggest that rigorous application of PBPK modeling to TCE risk assessment appears
      feasible at least for TCE and its major oxidative metabolites trichloroacetic
      acid and trichloroethanol. However, a number of basic structural hypotheses such
      as enterohepatic recirculation, plasma binding, and flow- or diffusion-limited
      treatment of tissue distribution require additional evaluation and analysis.
      Moreover, there are a number of metabolites of potential toxicologic interest,
      such as chloral, dichloroacetic acid, and those derived from glutathione
      conjugation, for which reliable pharmacokinetic data is sparse because of
      analytical difficulties or low concentrations in systemic circulation. It will be
      a challenge to develop reliable dosimetry for such cases.

PMID- 16966105
TI  - Key issues in the modes of action and effects of trichloroethylene metabolites
      for liver and kidney tumorigenesis.
AB  - Trichloroethylene (TCE) exposure has been associated with increased risk of liver
      and kidney cancer in both laboratory animal and epidemiologic studies. The U.S.
      Environmental Protection Agency 2001 draft TCE risk assessment concluded that it
      is difficult to determine which TCE metabolites may be responsible for these
      effects, the key events involved in their modes of action (MOAs) , and the
      relevance of these MOAs to humans. In this article, which is part of a mini
      monograph on key issues in the health risk assessment of TCE, we present a review
      of recently published scientific literature examining the effects of TCE
      metabolites in the context of the preceding questions. Studies of the TCE
      metabolites dichloroacetic acid (DCA) , trichloroacetic acid (TCA) , and chloral
      hydrate suggest that both DCA and TCA are involved in TCE-induced liver
      tumorigenesis and that many DCA effects are consistent with conditions that
      increase the risk of liver cancer in humans. Studies of S-(1,2-dichlorovinyl) -l
      cysteine have revealed a number of different possible cell signaling effects that
      may be related to kidney tumorigenesis at lower concentrations than those leading
      to cytotoxicity. Recent studies of trichloroethanol exploring an alternative
      hypothesis for kidney tumorigenesis have failed to establish the formation of
      formate as a key event for TCE-induced kidney tumors. Overall, although MOAs and
      key events for TCE-induced liver and kidney tumors have yet to be definitively
      established, these results support the likelihood that toxicity is due to
      multiple metabolites through several MOAs, none of which appear to be irrelevant
      to humans.

PMID- 16966106
TI  - Key issues in the role of peroxisome proliferator-activated receptor agonism and
      cell signaling in trichloroethylene toxicity.
AB  - Peroxisome proliferator-activated receptor alpha (PPARalpha) is thought to be
      involved in several different diseases, toxic responses, and receptor pathways.
      The U.S. Environmental Protection Agency 2001 draft trichloroethylene (TCE) risk
      assessment concluded that although PPAR may play a role in liver tumor induction,
      the role of its activation and the sequence of subsequent events important to
      tumorigenesis are not well defined, particularly because of uncertainties
      concerning the extraperoxisomal effects. In this article, which is part of a mini
      monograph on key issues in the health risk assessment of TCE, we summarize some
      of the scientific literature published since that time on the effects and actions
      of PPARalpha that help inform and illustrate the key scientific questions
      relevant to TCE risk assessment. Recent analyses of the role of PPARalpha in gene
      expression changes caused by TCE and its metabolites provide only limited data
      for comparison with other PPARalpha agonists, particularly given the difficulties
      in interpreting results involving PPARalpha knockout mice. Moreover, the increase
      in data over the last 5 years from the broader literature on PPARalpha agonists
      presents a more complex array of extraperoxisomal effects and actions, suggesting
      the possibility that PPARalpha may be involved in modes of action (MOAs) not only
      for liver tumors but also for other effects of TCE and its metabolites. In
      summary, recent studies support the conclusion that determinations of the human
      relevance and susceptibility to PPARalpha-related MOA(s) of TCE-induced effects
      cannot rely on inferences regarding peroxisome proliferation per se and require a
      better understanding of the interplay of extraperoxisomal events after PPARalpha
      agonism.

PMID- 16966107
TI  - Trichloroethylene cancer epidemiology: a consideration of select issues.
AB  - A large body of epidemiologic evidence exists for exploring causal associations
      between cancer and trichloroethylene (TCE) exposure. The U.S. Environmental
      Protection Agency 2001 draft TCE health risk assessment concluded that
      epidemiologic studies, on the whole, support associations between TCE exposure
      and excess risk of kidney cancer, liver cancer, and lymphomas, and, to a lesser
      extent, cervical cancer and prostate cancer. As part of a mini-monograph on key
      issues in the health risk assessment of TCE, this article reviews recently
      published scientific literature examining cancer and TCE exposure and identifies
      four issues that are key to interpreting the larger body of epidemiologic
      evidence: a) relative sensitivity of cancer incidence and mortality data ; b)
      different classifications of lymphomas, including non-Hodgkin lymphoma ; c)
      differences in data and methods for assigning TCE exposure status ; and d)
      different methods employed for causal inferences, including statistical or meta
      analysis approaches. The recent epidemiologic studies substantially expand the
      epidemiologic database, with seven new studies available on kidney cancer and
      somewhat fewer studies available that examine possible associations at other
      sites. Overall, recently published studies appear to provide further support for
      the kidney, liver, and lymphatic systems as targets of TCE toxicity, suggesting,
      as do previous studies, modestly elevated (typically 1.5-2.0) site-specific
      relative risks, given exposure conditions in these studies. However, a number of
      challenging issues need to be considered before drawing causal conclusions about
      TCE exposure and cancer from these data.

PMID- 16966108
TI  - Endogenous inhibitors of nitric oxide and preeclampsia: a review.
AB  - Nitric oxide (NO) is a potent vasodilator. NO is synthesized by NO synthases
      (NOS) and NOS are inhibited by asymmetrical dimethylarginine (ADMA). ADMA is
      metabolized by dimethylarginine dimethylaminohydrolase (DDAH) and excreted in the
      kidneys. Lower ADMA levels in pregnant women compared to non-pregnant controls
      suggest that ADMA has a role in vascular dilatation and blood pressure changes.
      Several studies show an increase in ADMA levels in pregnancies complicated with
      preeclampsia. Elevated ADMA levels in preeclampsia are seen before clinical
      symptoms have developed; these findings suggest that ADMA has a role in the
      pathogenesis of preeclampsia.

PMID- 16966109
TI  - Antibiotic administration to patients with preterm labor and intact membranes: is
      there a beneficial effect in patients with endocervical inflammation?
AB  - OBJECTIVE: To determine whether broad-spectrum antibiotic administration to
      patients with preterm labor and intact membranes is associated with an
      improvement in neonatal and maternal outcomes, particularly in patients with
      microbial invasion of the amniotic cavity (MIAC) or endocervical inflammation
      (ECI). METHODS: A prospective clinical trial was conducted in which women in
      premature labor were alternately allocated to receive either antibiotics or
      placebo, and information about MIAC and ECI collected. Eighty-four pregnant women
      between 24 and 34 weeks of gestation with spontaneous preterm labor were
      enrolled. Exclusion criteria were cervical dilatation greater than 3 cm, clinical
      chorioamnionitis, abruption, rupture of membranes, vaginal bleeding, and several
      additional fetal and maternal conditions that may influence perinatal outcome.
      Amniocentesis was offered to all patients and the cervix and vagina were sampled
      for microbiological and cytological studies. Eligible patients were allocated to
      receive either clindamycin-gentamycin or placebo for 7 days. Corticosteroids and
      tocolysis with beta-adrenergic agents were used according to the standard
      management of our institution. MIAC was defined as the presence of a positive
      amniotic fluid culture obtained by trans-abdominal amniocentesis. ECI was
      diagnosed when a significant increase in the white blood cell count of the
      endocervical secretions was found. A composite neonatal morbidity/mortality
      outcome was created, including severe neonatal morbidity (respiratory distress
      syndrome, asphyxia, sepsis, pneumonia, intraventricular hemorrhage) and
      mortality. RESULTS: Thirty-nine women received antibiotics and 40 received
      placebo. The prevalence of ECI and MIAC in both groups was comparable (antibiotic
      group ECI 61.5% (24/39) and MIAC 20.5% (8/39); placebo group ECI 62.5% (25/40)
      and MIAC 20% (8/40); p > 0.05). Overall, there were no significant differences in
      maternal infections and composite neonatal outcomes between antibiotic and
      placebo groups. Women who received antibiotics had a lower rate of subsequent
      rupture of membranes compared to patients who received placebo (2.6% (1/39) vs.
      25% (10/40), respectively; p = 0.007). A sub-analysis showed that among patients
      with ECI, antibiotic administration was associated with a lower rate of composite
      neonatal morbidity/mortality outcome compared to those who received placebo (4.2%
      (1/24) vs. 28% (7/25), respectively; p < 0.05). This association was also present
      in patients with ECI without MIAC (0% (0/16) vs. 27.8% (5/18); p < 0.05), but not
      in patients with ECI and MIAC (antibiotic group 12.5% (1/8) vs. placebo group
      28.6% (2/7); p > 0.05). CONCLUSIONS: The combination of antibiotics used in this
      study did not improve maternal or perinatal outcome in patients with preterm
      labor and intact membranes. Further studies are required to determine if women
      with endocervicitis presenting with preterm labor and intact membranes may
      benefit from antibiotic administration.

PMID- 16966110
TI  - A randomized controlled trial of acupuncture for initiation of labor in
      nulliparous women.
AB  - OBJECTIVE: To evaluate the utility of outpatient acupuncture for labor
      stimulation. METHODS: Nulliparous women at 39 4/7 weeks or greater with a
      singleton gestation and Bishop score of less than 7 were randomized to usual
      medical care (control group) versus usual care and three outpatient acupuncture
      treatments (acupuncture group). Each treatment consisted of eight needles applied
      to bilateral points LI4, SP6, UB31, and UB32. The primary outcome was time
      elapsed from the time of randomization to delivery. Secondary outcomes included
      rates of cesarean section and induction of labor. Medical records were abstracted
      for maternal demographic, medical, and delivery outcome data. A priori sample
      size calculation revealed that 56 women were required to detect a 72-hour
      difference in delivery time with a power of 83% and an alpha of 0.05. Student's t
      test, Chi-square, and Kaplan-Meier statistics were used to compare groups.
      RESULTS: Fifty-six women were randomized and completed the study procedures.
      Race, age, gestational age, and cervical Bishop score were similar in both
      groups. Mean time to delivery occurred 21 hours sooner in the acupuncture group,
      but this difference did not reach statistical significance (p = 0.36). Compared
      to controls, women in the acupuncture group tended to be more likely to labor
      spontaneously (70% vs. 50%, p = 0.12) and less likely to deliver by cesarean
      section (39% vs. 17%, p = 0.07). Of women who were not induced, those in the
      acupuncture group were more likely to be delivered than the controls at any point
      after enrollment (p = 0.05). CONCLUSION: Acupuncture is well tolerated among term
      nulliparous women and holds promise in reducing interventions that occur in post
      term pregnancies.

PMID- 16966111
TI  - Induction of labor: comparison of a cohort with uterine scar from previous
      cesarean section vs. a cohort with intact uterus.
AB  - OBJECTIVE: To compare the risk of uterine rupture between a cohort of women with
      previous low-transverse cesarean section (CS) and a cohort with intact uterus.
      METHODS: All women with a singleton pregnancy and previous low-transverse CS
      requiring induction of labor from January 1, 1992 to December 30, 2001 (n = 310)
      were compared with a cohort of women with intact uterus undergoing induction of
      labor during the same study period (n = 5420). Protocols of induction using
      prostaglandin E2 gel and oxytocin infusion were consistent within groups, but
      differed between the previous CS and the intact uterus group. RESULTS: Uterine
      rupture occurred in 0.3% in the previous CS group vs. 0.03% in the intact uterus
      group (p = 0.37). Logistic regression analysis showed no significant difference
      in rate of uterine rupture between the previous CS vs. intact uterus group (p =
      0.16) after controlling for maternal age, parity, gestational age at delivery,
      Bishop score on admission, use of prostaglandin and oxytocin, and birth weight.
      Our study had adequate power to detect a 0.38% difference in rate of uterine
      rupture between the two groups (alpha = 0.05, beta = 0.80). CONCLUSION: Induction
      of labor is not associated with significantly higher rates of uterine rupture
      among women with previous low-transverse CS compared with women with intact
      uterus provided a consistent protocol with strict intervention criteria is
      adopted.

PMID- 16966112
TI  - Trypsin and antitrypsin activities and protein concentration in serial meconium
      and feces of healthy newborns.
AB  - BACKGROUND: Meconium has the potential for being the matrix on which markers of
      fetal exposure to physiologic and non-physiologic agents during intrauterine life
      can be analyzed. The aim of this study was to compare trypsin and antitrypsin
      activities and protein concentration during intra- and extrauterine human
      development based on an assessment of these parameters in serial meconium and
      first feces of healthy, term newborns during the first four days of life.
      METHODS: One hundred and eighteen mature, term newborns were studied. Single
      portions of meconium or feces were taken prospectively from day 1 to day 4. In
      ten newborns each meconium and feces passed by the infant from birth up to the
      fourth day after delivery was collected individually. Trypsin activity was
      measured using L-TAPA (N-alpha-tosyl-l-arginine-p-nitroanilide) as substrate,
      trypsin inhibitory capacity (TIC) with N-alpha-benzoyl-dl-arginine-p-nitroanilide
      (BAPNA) as substrate, and protein concentration by the method of Lowry et al.
      RESULTS: Meconium and feces of healthy newborns demonstrated a decrease in TIC
      during the first two days of life and an increase in trypsin activity over the
      first three successive days of life. No correlation was observed between the
      variability of both parameters. During the first three days of a newborn's life,
      significant correlation was observed between TIC and protein concentration in
      meconium and first feces. In the course of proteolytic activity changes in
      successive portions of meconium and feces, a transient peak occurs on the 2nd-4th
      day of life. CONCLUSIONS: The gradual decrease in protease inhibitor activity and
      low trypsin activity in successive portions of meconium from the first two days
      of extrauterine life may provide a retrograde chronological depiction of the
      course of the second and third trimesters of intrauterine life. Serial collection
      of feces over 2-4 days may provide a reflection of the dynamics of the postnatal
      increase in the newborn's pancreatic exocrine functions.

PMID- 16966113
TI  - Ethnic disparity in the success of vaginal birth after cesarean delivery.
AB  - OBJECTIVE: To estimate whether maternal race/ethnicity is independently
      associated with successful vaginal birth after cesarean delivery (VBAC). STUDY
      DESIGN: A retrospective cohort study from January 1, 1997 to July 30, 2002 of
      women with singleton pregnancies and a previous cesarean delivery. The odds ratio
      (OR) for successful VBAC as a function of ethnicity was corrected for age >35
      years, parity, weight gain, diabetes mellitus, hospital site, prenatal care
      provider, gestational age, induction, labor augmentation, epidural analgesia, and
      birth weight >4000 g. RESULTS: Among 54 146 births, 8030 (14.8%) occurred in
      women with previous cesarean deliveries. The trials of labor rates were similar
      among Caucasian (46.6%), Hispanic (45.4%), and African American (46.0%) women.
      However, there was a significant difference among ethnic groups for VBAC success
      rates (79.3% vs. 79.3% vs. 70.0%, respectively). When compared to Caucasian
      women, the adjusted OR for VBAC success was 0.37 (95% confidence interval (CI)
      0.27-0.50) for African American women and 0.63 (95% CI 0.51-0.79) for Hispanic
      women. CONCLUSION: African American and Hispanic women are significantly less
      likely than Caucasian women to achieve successful VBAC.

PMID- 16966114
TI  - Effect of maternal dexamethasone and alpha-ketoglutarate administration on
      skeletal development during the last three weeks of prenatal life in pigs.
AB  - BACKGROUND: The effect of dexamethasone (Dex) on postnatal bone formation
      processes is known to decrease the synthesis of collagen and bone matrix, but the
      effect of alpha-ketoglutarate (AKG) is to induce positive effects on growth and
      skeletal development during postnatal life. However, the effects of Dex and AKG
      treatment on the prenatal processes of skeletal development have not been
      investigated so far. OBJECTIVE: The aim of this study was to determine the effect
      of Dex and AKG administered separately or simultaneously to sows during the last
      three weeks of pregnancy on the skeletal development in fetuses. METHODS:
      Immediately after birth blood samples were collected from non-suckling piglets
      for alkaline phosphatase and osteocalcin determinations, and the humeri were
      isolated. Bone mineral density (BMD) and bone mineral content (BMC) of humeri and
      the geometric and mechanical properties were evaluated. RESULTS: Dex and AKG
      administered separately to pregnant sows during the last 24 days of prenatal life
      decreased BMD, BMC, and geometric and mechanical parameters of humeri in the
      newborns. Simultaneous administration of Dex and AKG significantly increased the
      analyzed properties of humeri. CONCLUSION: The bone mineral density and
      mechanical and geometric properties of humeri indicate an inverse effect of
      maternal separate or simultaneous administration of AKG and Dex to sows on bone
      development during the last 24 days of prenatal life.

PMID- 16966115
TI  - Chronic effects of maternal smoking on pulse waves in the fetal aorta.
AB  - OBJECTIVE: In order to evaluate the impact of maternal smoking on arterial
      stiffness in utero, pulse wave characteristics in the fetal aorta were
      investigated. A prospective clinical study was made of 34 smoking and 34 non
      smoking healthy volunteers with uncomplicated pregnancies at 31-40 weeks of
      gestation. METHODS: The mechanical properties of the fetal thoracic aorta were
      assessed by an ultrasonic phase-locking echo-tracking system. For each fetus with
      a smoking mother, a non-smoking control matched for gestational and maternal age
      was monitored. Women with later appearing pregnancy complications were excluded.
      Pulse wave velocity (PWV), maximum diameter in systole (Ds), end-diastolic
      diameter (Dd), pulse amplitude (DeltaD), and maximum incremental velocity (MIV)
      in the fetal aorta were measured and analyzed in relation to maternal smoking and
      gestational age. RESULTS: Results were computed on fetuses of 32 smokers and 30
      non-smokers. PWV increased with gestational age in smokers (corr. coeff. 0.49, p
      < 0.006) but not in non-smokers (corr. coeff. -0.12). MIV did not change in
      smokers (corr. coeff. -0.15) but increased in non-smokers (corr. coeff. 0.40, p <
      0.03). Differences in regression lines between the groups regarding PWV and MIV
      were significant (p < 0.02 for both). CONCLUSIONS: Maternal smoking seems to
      promote the stiffening of the fetal aorta during gestation.

PMID- 16966116
TI  - Audit of perinatal deaths in a tertiary level hospital in Latvia (1995-1999)
      using the Nordic-Baltic perinatal death classification: evidence of suboptimal
      care.
AB  - OBJECTIVE: The objective of this study was to explore applicability of the Nordic
      Baltic perinatal death (PND) classification in a single hospital via evaluation
      of changes of the preventability of PND over the time period in a tertiary level
      perinatal care center in Latvia. METHOD: All PND cases during the period 1995
      1999 at a tertiary referral perinatal care center, the Riga Maternity Hospital
      (RMH), were analyzed using the common Nordic-Baltic PND classification. RESULTS:
      The total perinatal mortality rate (PNMR) did not decline at the RMH over the
      study period. The rate of antenatal and intrapartum deaths at <28 weeks of
      gestation increased (p < 0.01). Early neonatal deaths at 28-33 weeks of gestation
      with a low 5-minute Apgar score became less frequent (p < 0.05). There was a
      trend towards more cases of probably suboptimal care (p < 0.005) and the
      proportion of preventable PND cases increased from 14.7% in 1995 to 36.4% in 1999
      (p = 0.01). CONCLUSION: The perinatal audit performed at the RMH using the Nordic
      Baltic PND classification disclosed a requirement for further improvement of
      perinatal care in the hospital. The classification can be used to evaluate the
      preventability of perinatal death cases in a single hospital, and its application
      in other hospitals in Latvia could provide information necessary for the
      improvement of perinatal care in the country.

PMID- 16966117
TI  - Tissue microarray: an effective high-throughput method to study the placenta for
      clinical and research purposes.
AB  - OBJECTIVE: Tissue microarray (TMA) technology allows simultaneous examination of
      the expression of many molecular markers (protein, mRNA, DNA, etc.) with high
      throughput. The application of this technology, to date, has been largely
      confined to the study of cancer. Placental pathology poses unique challenges
      because of the size of the organ, its complex anatomy, as well as its
      histological heterogeneity. The objective of this study was to assess the
      feasibility and efficiency of TMAs for immunohistochemistry and in situ
      hybridization of placental tissues. STUDY DESIGN: TMAs were constructed using an
      automated tissue arrayer. Standard 0.6-mm or 1-mm microarray needles were used.
      Villous parenchyma, basal plate, and chorioamniotic membranes were targeted in
      each block. Five mum-thick TMA sections underwent immunohistochemical analysis of
      both cytoplasmic and nuclear antigens using a panel of antibodies against a
      variety of cytoplasmic [cytokeratin-7, vascular endothelial growth factor (VEGF),
      and protein Z], membranous (endoglin), and nuclear (c-fos and c-jun) antigens.
      mRNA in situ hybridization for surfactant protein A (SP-A) and chromogenic in
      situ hybridization for the Y chromosome (DYZ1) were also performed. RESULTS:
      Validation of TMA immunoreactivity demonstrated comparable results with
      corresponding whole sections. When a two-tiered scoring system
      (positive/negative) was employed, there was agreement between two and three cores
      and whole tissue sections (kappa>0.7). When a three-tiered scoring system
      (negative, weak-positive, or strong-positive) was used, the data from three cores
      showed the highest agreement with whole tissue sections (kappa >0.7). In situ
      hybridization experiments for mRNA and DNA were also successful in that the
      signals were readily detectable. Successful transfer from the donor block to the
      recipient block differed according to the anatomical compartment. The transfer
      efficiency of villous parenchyma, basal plate, and chorioamniotic membranes were
      96.9% (875/903), 76.7% (115/150), and 75.4% (224/297), respectively. CONCLUSION:
      TMA is a practical and effective tool for high-throughput molecular analysis of
      the human placenta. Duplicate and triplicate cores offer agreement with whole
      tissue sections for two-category distinction immunostaining. TMA also affords
      relevant results from in situ hybridization experiments for mRNA and DNA. The
      major advantages are the conservation of tissues and reagents, simultaneous
      comparison of molecular markers in different anatomical compartments of the
      placenta, and reduction of experimental error.

PMID- 16966118
TI  - The management of feto-maternal alloimmune thrombocytopenia: report of three
      cases.
AB  - We report herein three cases of severe fetal thrombocytopenia due to anti-human
      platelet antigen (HPA)- 1a maternal antibodies. The first and the third cases
      were diagnosed on the basis of previously affected siblings and treated
      successfully by maternal intravenous human immunoglobulins and corticosteroids.
      In the second case an unexpected neonatal thrombocytopenia was found after birth
      without previously affected siblings and treated subsequently with intravenous
      immunoglobulins. Our experience supports a switch from an invasive management,
      including early FBS (fetal blood sampling) and platelet transfusions, to a more
      cautious approach. Also in severe HPA-1a alloimmunization and in 'high risk'
      fetuses, prenatal maternal treatment could be performed, without previous FBS,
      only on the basis of a risk score defined by sibling history and parents'
      genotypes.

PMID- 16966119
TI  - Periodontal disease and adverse pregnancy outcomes.
AB  - Periodontal disease is a common infectious disease in women of reproductive age.
      The disease is often not diagnosed and in studies of over 10 000 women has been
      associated with preterm birth, small for gestational age newborns, and
      preeclampsia. It has been shown in a smaller number of women that treatment of
      periodontal disease may reduce the rate of preterm birth. The pregnancy
      complications of periodontal disease may be due to lipopolysaccharide from the
      periodontal pockets inciting prostaglandin pathways controlling parturition.
      Three large randomized controlled trials of treatment of periodontal disease are
      underway and may provide confirmation of the importance of periodontal disease in
      causing complications of pregnancy.

PMID- 16966120
TI  - Fetal plasma cortisol and dehydroepiandrosterone sulfate concentrations in
      pregnancy and term parturition.
AB  - OBJECTIVE: To examine if changes in fetal plasma concentrations of cortisol or
      dehydroepiandrosterone sulfate (DHEAS) levels are associated with human term
      parturition. METHODS: Umbilical cord plasma cortisol and DHEAS concentrations
      were measured in 374 singleton pregnancies that delivered at term in the
      following six groups: group 1, cordocentesis for clinical indications before 36
      weeks of gestation (n = 93); group 2, cordocentesis for clinical indications
      after 36 weeks of gestation (n = 9); group 3, cord blood sampling after elective
      cesarean section (CS) at term without labor (n = 140); group 4, cord blood
      sampling after CS at term with early labor (cervical dilatation < or =3 cm, n =
      18); group 5, cord blood sampling after CS at term with active labor (cervical
      dilatation 4 cm or greater, n = 26); group 6, cord blood sampling after vaginal
      delivery at term (n = 88). Corticosteroids were not administered before blood
      collection. RESULTS: (1) Fetal plasma cortisol remained unchanged until 36 weeks
      of gestation and increased thereafter to term; (2) active labor was associated
      with a significant increase in fetal plasma cortisol; (3) fetal plasma DHEAS
      increased at term gestation (>36 weeks) but did not increase during active labor;
      (4) the cortisol/DHEAS ratio (stress index) increased with advancing gestation
      and with active labor at term. CONCLUSIONS. Human parturition at term is
      associated with an increase in fetal plasma cortisol and in the cortisol/DHEAS
      ratio, but not in DHEAS.

PMID- 16966121
TI  - Possible association between maternal recurrent orofacial herpes in pregnancy and
      a lower rate of preterm birth.
AB  - OBJECTIVE: To study the possible association between orofacial herpes during
      pregnancy and pregnancy complications including preterm birth and low birth
      weight, since the results of previous studies are inconsistent. METHOD: The
      population-based large data set of the Hungarian Case-Control Surveillance System
      of Congenital Abnormalities was used; pregnancies in mothers with and without
      recurrent orofacial herpes were compared. RESULTS. Of 38,151 newborn infants, 572
      (1.5%) had mothers with recurrent orofacial herpes during pregnancy, while 37 577
      had mothers with no orofacial herpes. Pregnant women with recurrent orofacial
      herpes had a higher prevalence of severe nausea and vomiting, threatened preterm
      delivery, and placental disorders but a lower prevalence of preeclampsia. Mothers
      with recurrent orofacial herpes during pregnancy also had a somewhat longer (0.4
      weeks) gestation (adjusted t = 2.7; p = 0.006) and an obviously lower proportion
      of preterm births (3.5% vs. 9.3%; adjusted POR with 95% CI = 0.42, 0.27-0.65).
      However, there was no significant difference in the mean birth weight and rate of
      low birth weight infants between the two study groups. CONCLUSION: Recurrent
      orofacial herpes during pregnancy is associated with a smaller proportion of
      preterm births.

PMID- 16966122
TI  - Low-molecular-weight heparin for thromboprophylaxis in pregnant women with
      mechanical heart valves.
AB  - BACKGROUND: Pregnancy in a woman with a mechanical heart valve is a life
      threatening situation. Due to the inability of unfractionated heparin to prevent
      valvular thromboses, warfarin or other vitamin K antagonists have been the
      preferred anticoagulants for the mother. They are, however, potentially harmful
      to the fetus. With the advent of low-molecular-weight heparins, clinicians were
      hopeful for an alternative that was safe for the fetus, but more effective than
      unfractionated heparin, which carries a 29-33% risk of life-threatening
      thromboses and a 7-15% chance of mortality. Unfortunately, fatal thromboses have
      occurred with low-molecular-weight heparin as well. METHODS: We searched the
      MEDLINE database and other sources to identify cases of the use of low-molecular
      weight heparin for thromboprophylaxis in women with mechanical heart valves.
      RESULTS: We found 73 cases and added three of our own for a total of 76. There
      were 17 thrombotic events (22%). Thirteen were valve thromboses, two were
      strokes, and two were myocardial infarctions. There were three deaths (4%).
      CONCLUSIONS: While pregnant women with mechanical heart valves who receive low
      molecular-weight heparin for thromboprophylaxis are at extremely high risk of
      life-threatening thromboses, there is no evidence that low-molecular-weight
      heparin is inferior to unfractionated heparin.

PMID- 16966123
TI  - Evaluation of third trimester uterine artery flow velocity indices in
      relationship to perinatal complications.
AB  - OBJECTIVE: Uterine artery Doppler is becoming a routine part of pregnancy
      surveillance in high-risk pregnancies. Which blood flow velocity waveform index
      to measure is debated and the 'notch' in early diastole is not widely accepted,
      as it is a subjective measure. The aim of the present study was to evaluate the
      different indices in the prediction of adverse outcome of pregnancies suspected
      for intrauterine fetal growth restriction (IUGR). METHODS: Uterine artery blood
      flow was recorded in 217 pregnancies admitted for Doppler ultrasound surveillance
      due to suspected IUGR. The median gestational age at examination was 38 weeks
      (range 25-42 weeks). Only cases having bilateral uterine artery notching were
      included in the evaluation. The uterine artery Doppler spectrum was analyzed for
      different indices, including evaluation of notch and end-diastolic velocities.
      Umbilical artery Doppler velocimetry was also performed. The outcome variables
      chosen were: a small-for-gestational-age (SGA) newborn, preterm birth, and
      abdominal delivery. ROC-curve calculations were used to compare the different
      indices. RESULTS: The uterine artery blood velocity pulsatility index (PI) and
      resistance indices (RI) were the best predictors of adverse outcome of pregnancy.
      Apart from premature birth, the systolic/end-diastolic ratio was less predictive
      of adverse outcome. The indices including only diastolic blood velocities were
      the least predictive of adverse outcome. The group with notch velocity above end
      diastolic velocity was compared with those having notch velocity below the end
      diastolic velocity. No difference in outcome was seen between the two groups.
      CONCLUSIONS: RI and PI as measures of third trimester utero-placental vascular
      impedance are the best predictors of adverse outcome of IUGR-suspected
      pregnancies.

PMID- 16966124
TI  - Suspicion of intrauterine growth restriction: Use of abdominal circumference
      alone or estimated fetal weight below 10%.
AB  - OBJECTIVE: To determine, among patients at risk for intrauterine growth
      restriction (IUGR), the peripartum outcomes and predictive accuracy for those
      with normal abdominal circumference (AC) and estimated fetal weight (EFW) for
      gestational age (GA; group 1) versus those with AC < or = 10% for GA but EFW>10%
      (group 2) versus those with AC and EFW < or = 10% for GA (group 3). STUDY DESIGN:
      We identified, retrospectively, non-anomalous singleton pregnancies with reliable
      GA, and delivery within 21 days of the examination who were referred for possible
      IUGR. Odds ratios (OR) and 95% confidence intervals (CI) were calculated, as were
      likelihood ratios (LR) for detection of small for gestational age (SGA) (birth
      weight < or = 10% for GA; SGA). RESULTS: Among the 169 consecutive patients who
      met the inclusion criteria, the prevalence of SGA was significantly higher for
      group 3 (80%) than group 1 (42%; OR 4.26, 95% CI 1.94-9.16) or group 2 (49%; OR
      5.49, 95% CI 2.13-13.85). The rate of admission to the neonatal intensive care
      unit (67%, 34%, and 36% for groups 3, 2, and 1, respectively) and the combined
      perinatal morbidity (35%, 23%, and 15%) were different for the three groups. The
      LR for detection of SGA was 1.2 (95% CI 1.0-1.4) for group 2 and 2.8 (95% CI 1.6
      4.9) for group 3. CONCLUSIONS: Among patients suspected for IUGR, the peripartum
      outcome is poorest for those with AC and EFW < or = 10% for GA, than for those
      with AC < or = 10% but EFW>10%. The detection of SGA is poor regardless of
      whether just AC or AC plus EFW are < or = 10%.

PMID- 16966125
TI  - Associated factors and outcomes of persistent occiput posterior position: A
      retrospective cohort study from 1976 to 2001.
AB  - OBJECTIVE: To identify maternal and fetal risk factors associated with persistent
      occiput posterior position at delivery, and to examine the association of occiput
      posterior position with subsequent obstetric outcomes. METHODS: This is a
      retrospective cohort study of 30 839 term, cephalic, singleton births. Women with
      persistent occiput posterior (OP) position at delivery were compared to those
      with occiput anterior (OA) position. Demographics, obstetric history, and labor
      management were evaluated and subsequent obstetric outcomes examined. Potential
      confounding variables were controlled for using multivariate logistic regression
      analysis. RESULTS: The overall frequency of OP position was 8.3% in the study
      population. When compared to Caucasians, a higher rate of OP was observed among
      African-Americans (OR = 1.4, 95% CI 1.25-1.64) while no other racial/ethnic
      differences were noted. Other associated factors included nulliparity, maternal
      age > or =35, gestational age > or =41 weeks, and birth weight >4000 g, as well
      as artificial rupture of the membranes (AROM) and epidural anesthesia (p < 0.001
      for all). Persistent OP was associated with increased rates of operative vaginal
      (OR = 4.14, 95% CI 3.57-4.81) and cesarean deliveries (OR = 13.45, 95% CI 11.94
      15.15) and other peripartum complications including third or fourth degree
      perineal lacerations (OR = 2.38, 95% CI 2.03-2.79), and chorioamnionitis (OR =
      2.10, 95% CI 1.81-2.44). CONCLUSION: Epidural use, AROM, African-American
      ethnicity, nulliparity, and birth weight >4000 g are associated with persistent
      OP position at delivery, with higher rates of operative deliveries and obstetric
      complications. This information can be useful in counseling patients regarding
      risks and associated outcomes of persistent OP position.

PMID- 16966126
TI  - Delivery room strategies and outcomes in preterm infants with gestational age 24
      28 weeks.
AB  - OBJECTIVE: To investigate the effect of different delivery room strategies on
      survival, short term morbidity, and outcomes in extremely premature infants.
      METHODS: This retrospective cohort study included all preterm infants with a
      gestational age between 24 and 28 weeks who were born in 1992-1997 (period A; n =
      161) and in 1998-2003 (period B; n = 163). In period A, elective intubation was
      performed. In period B, if spontaneous breathing was present, nasal continuous
      positive airway pressure (nCPAP) was applied. RESULTS: Survival rate and the
      number of never-intubated infants significantly increased in period B. No
      differences were found concerning short-term morbidity. Among major outcomes, the
      need for retinopathy of prematurity (ROP) surgery and the length of stay were
      significantly lower in period B. Subgroup analysis showed no significant
      differences from period A to period B in infants with gestational age 24-26
      weeks. In the 27-28 weeks subgroup, the never-intubated infants rate increased
      from 2.8% to 21.3% and survival rate increased from 63% to 79%. A reduced need
      for ROP surgery and a shorter hospital stay were also observed. CONCLUSIONS:
      Changes in delivery room strategy tending to reduce mechanical ventilation in
      extremely premature infants are likely to benefit essentially infants of 27-28
      weeks of gestation. Extension of such benefits to premature infants at the limit
      of viability requires further research.

PMID- 16966127
TI  - Is routine prophylactic cervical cerclage associated with significant
      prolongation of triplet gestation?
AB  - OBJECTIVE: The purpose of this study was to determine if routine prophylactic
      cervical cerclage was associated with a significant prolongation of triplet
      pregnancy. STUDY DESIGN: A retrospective study of all women carrying triplet
      pregnancies at a single institution during a four-year period was carried out.
      Selected maternal characteristics and obstetric outcome measures in women who
      received prophylactic cerclage (PC) were compared to women who did not receive PC
      (no cerclage placed and emergency cerclage). Statistical comparison was done
      using the Mann-Whitney test for continuous variables and Fisher's exact test for
      categorical variables. RESULTS: Fifty-five women had PC and 40 had no PC. There
      was no significant difference between these two groups in mean maternal age or
      weight, nulliparity, history of or current sexually transmitted disease,
      cigarette smoking, history of cervical insufficiency, prior dilation and
      curettage, prior cervical surgery, prior preterm labor/prolonged preterm rupture
      of membranes (PTL/PPROM), medical complications in pregnancy, current PTL/PPROM,
      gestational age at delivery, delivery prior to 28 weeks, delivery prior to 32
      weeks, or delivery of an infant weighing less than 1000 or 1500 grams. Thirteen
      women in the no PC group (32.5%) required emergency cerclage. CONCLUSION: PC was
      not associated with significant prolongation of triplet pregnancy.

PMID- 16966128
TI  - Treatment of pulmonary hypertension with sildenafil in a neonate with
      spondyloepiphyseal dysplasia congenita.
AB  - Persistent pulmonary hypertension of the newborn (PPHN) remains an important
      cause of mortality and morbidity in the term neonate. Preliminary but limited
      data suggest that there may be a role for sildenafil in the treatment of PPHN. We
      report the successful treatment of PPHN caused by pulmonary hypoplasia in a
      patient with spondyloepiphyseal dysplasia congenita.

PMID- 16966129
TI  - Abruptio placentae and idiopathic arterial calcification in a stillborn.
AB  - We report a case of idiopathic arterial calcification in a stillborn of 22 weeks
      gestational age. The pregnancy was complicated by abruptio placentae and the
      postmortem examination showed widespread arterial calcification in the placenta,
      as well as in the pulmonary, renal, cerebellar, and brain arteries.

PMID- 16966130
TI  - Mitochondrial respiratory chain defects and developmental diaphragmatic
      dysfunction in the neonatal period.
AB  - Mitochondrial respiratory chain disorders are increasingly recognized as common
      causes of neurological disease and can present at any time from birth through to
      later in adult life. Although presentation in the neonatal period is rare and few
      syndromes are described, an association between mitochondrial dysfunction and
      diaphragmatic problems presenting in the neonatal period has not previously been
      reported in the literature. Here we report a case series of three newborns that
      were ventilator-dependent with abnormal diaphragms and became acidotic when
      required to perform the work of breathing. All were later confirmed to have a
      mitochondrial respiratory chain disorder following biochemical investigations of
      muscle tissue, raising the possibility of a link between mitochondrial
      dysfunction and diaphragmatic involvement.

PMID- 16966131
TI  - Accelerating biomedical engineering in Japan--the TUBERO project.

PMID- 16966132
TI  - High maneuverability guidewire with functionally graded properties using new
      superelastic alloys.
AB  - Nitinol shape memory alloys (SMAs) are attracting considerable attention as core
      materials for medical guidewires because of their excellent flexibility and shape
      retention. However, since Nitinol guidewires possess low rigidity, the
      pushability and torquability of the guidewires are insufficient. On the other
      hand, although guidewires made of stainless steel have high pushability, plastic
      deformation occurs easily. We have developed a new class of superelastic
      guidewires with functionally graded properties from the tip to the end by using
      new SMA core materials such as Cu-Al-Mn-based or Ni-free Ti-Mo-Sn SMAs. The tip
      portion of the guidewire shows excellent superelasticity (SE), while the body
      portion possesses high rigidity. These functionally graded characteristics can be
      realized by microstructural control. These guidewires with functionally graded
      properties show excellent pushability and torquability and are considerably
      easier to handle than conventional guidewires with Nitinol or stainless steel
      cores. Moreover, a metallic catheter using a Ni-free Ti-based SMA with high
      biocompatibility is introduced.

PMID- 16966133
TI  - Development of amyloid imaging PET probes for an early diagnosis of Alzheimer's
      disease.
AB  - Progressive accumulation of senile plaques (SPs) is one of the major
      neuropathological features of Alzheimer's Disease (AD) that precedes cognitive
      decline. Noninvasive detection of SPs could, therefore, be a potential diagnostic
      test for early or presymptomatic detection of AD patients. For this purpose, many
      attempts have been made to visualize AD-specific pathological changes in the
      living brain. Currently, a most practical method for the in vivo measurement of
      SP depositions is using positron emission tomography (PET) and contrast agent
      that specifically label SPs. We have developed a novel compound 2-[2-(2
      dimethylaminothiazol-5-yl) ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole (BF-227) as
      a candidate for an amyloid imaging probe for PET. BF-227 displayed high affinity
      to synthetic amyloid beta fibrils and clearly stained both SPs and diffuse
      plaques in AD brain sections. Intravenous administration of [11C]BF-227 into
      normal mice indicated that this labeled tracer readily penetrated the blood brain
      barrier (BBB) and was washed out quickly from brain tissue. Currently, we have
      investigated the clinical trial of [11C]BF-227 in healthy subjects and AD
      patients.

PMID- 16966134
TI  - Measurement method for the fetal electrocardiogram.
AB  - A fetal electrocardiogram (ECG) provides clinically significant information
      concerning the electrophysiological states of a fetus. Since the first attempt by
      Cremer in 1906, for about 100 years nobody has been able to non-invasively
      extract the fetal ECG popularly used in clinical situations. The low amplitude of
      the fetal signals and the high background noise and the non-linearity of the ECG
      signals mainly have been interfering with the noninvasive extraction of the fetal
      ECG. The aim of this paper is to introduce a new nonlinear filtering method to
      extract the fetal electrocardiogram detected from the mother's abdominal wall.
      This method consists of two steps: The rough extraction step performed by blind
      source separation (BSS) with references and the precise extraction step with fast
      non-linear state space projection (FNSSP) based on a nonlinear state space
      projection (NSSP), which needs several complicated conditions or has limitations.
      So, it takes a lot of time to calculate. Our new method does not require such
      conditions, and it has about a thirty-fold speedup when compared with the
      previous method. Our new method has been successfully applied to on-line
      recordings with fetal components and will be useful for monitoring the fetal
      electrocardiogram in clinical applications.

PMID- 16966135
TI  - Minimally invasive diagnostics and treatment using micro/nano machining.
AB  - Several medical tools with various functions have been developed for minimally
      invasive diagnostics and treatment. Microfabrication techniques such as MEMS
      technology are useful for the realization of high-performance multifunctional
      minimally invasive medical tools with small sizes. An ultra-miniature pressure
      sensor and an intravascular ultrasonic forward-viewing imager have been developed
      as microsensors for use in the human body. Active bending catheters have been
      developed for steering catheter tips without using traction of wires from outside
      the body. An ultrasonic therapeutic tool for sonodynamic therapy and
      sonoporation, and a micro scanner for precise laser treatment have been developed
      as therapeutic tools for use in the human body. High-functionalized endoscopic
      tools and catheters will enable more precise and safe diagnostics and therapy, as
      well as novel diagnostics and treatment which have been impossible to date.

PMID- 16966136
TI  - A non-invasive tissue-specific molecular delivery method of cancer gene therapy.
AB  - A Japanese word, monozukuri (literally translated "making things") is the
      philosophy of first having the idea and then the faith in the technical expertise
      and experience to accomplish the result. We believe that the concept of
      engineering is monozukuri. Through the process of monozukuri, engineered natural
      science based on mathematics and physics has been developed. Medicine is the
      field of study which has been developed for maintaining daily healthy life with
      diagnosis, treatment, examination, and protection. Biomedical engineering is the
      interdisciplinary study of engineering and medicine, and should be developed
      based on monozukuri. In this particular research, we have developed a physical
      molecular delivery method for cancer gene therapy using nano/microbubbles and
      ultrasound. First, the behavior of cavitation bubbles and subsequent shock wave
      phenomena involved in the mechanism of molecular delivery were analyzed,
      combining theory and computer simulation. In a second step, the methodology was
      optimized in vitro and in vivo. Finally, the therapeutic potential of the method
      in pre-clinical models was evaluated using transgenes relevant to cancer gene
      therapy instead of reporter genes, and whole body, non-invasive imaging using
      single photon emission computed tomography (SPECT/CT) was used to evaluate the
      selectivity of gene delivery in vivo.

PMID- 16966137
TI  - Development of shock wave assisted therapeutic devices and establishment of shock
      wave therapy.
AB  - In order to exploit systems for shock wave therapy, we are working for the
      development of clinical devices that are based on the concept of shock waves or
      related phenomena. The paper describes these new therapeutic devices designed for
      the minimally invasive approach to vascular thromboloysis, selective dissection
      of tissues, and drug or DNA delivery. To investigate the response of cells to
      shock loading, a precise method of shock waves generation in space and time has
      been developed. This method has been studied for application in cardiovascular
      therapy, cancer treatment, and cranioplasty in close vicinity of the brain. A
      laser ablation shock wave assisted particle acceleration device has been
      developed for delivering drug and DNA into soft targets in the human body. The
      penetration depth of microparticles observed in the experimental targets is
      believed to be sufficient for pharmacological treatments. In order to achieve an
      efficient method for rapid revascularization of cerebral thrombosis, a laser
      induced liquid jet (LILJ) system has been developed. The LILJ has been
      successfully applied for selective dissection of soft tissue preserving nerve and
      blood vessels. The system has been further improved by using piezoelectric
      actuators to drive the liquid jets, as an alternative to pulse laser.

PMID- 16966138
TI  - Preclinical development of SMA artificial anal sphincters.
AB  - This article presents some progress in the development for preclinical trials of
      an artificial anal sphincter using shape memory alloys. The novel device has been
      proposed and developed by the author's group at Tohoku University. It has two
      dominant features different from other systems, which are either clinically
      available or still under development. One is that a solid driving element, a
      combination of shape memory alloy (SMA) ribbons and silicone elastomer sheets
      with a layered structure, is adopted for the opening and closing functions of the
      artificial sphincter. The other is a sandwich mechanism for the closing of bowel
      to reduce the risk of buckling induced ischemia which has been reported in
      hydraulically driven artificial sphincters with a radial squeezing mechanism. The
      device has fewer parts inside the body and therefore be implanted more easily. A
      new design eliminating the risk of heat burns enables long-term implantation and
      brings the device closer to practical use. Functionality and safety of the device
      have been proved in three-month animal experiments.

PMID- 16966139
TI  - Adipose precursor cells (preadipocytes) induce formation of new vessels in fibrin
      glue on the newly developed cylinder chorioallantoic membrane model (CAM).
AB  - Successful augmentation of soft tissues by transplantation of preadipocytes
      within a matrix requires the formation of a new capillary network with connection
      to the host vessel system. Particularly, cells located centrally within the
      transplanted cell-matrix-construct represent a population with a blood supply
      questionable for survival. We demonstrated that under in vivo conditions
      preadipocytes possess the ability to induce and support the vascularization of
      the implant presumably by expression of several growth factors, such as VEGF
      (vascular endothelial growth factor) and bFGF (basic fibroblast growth factor).
      Fertilized White-Leghorn eggs were incubated under standardized conditions.
      Opening was performed at day three of incubation and preadipocytes with and
      without recombinant growth factors were transferred into a fibrin matrix and
      subsequently placed on the Chorioallantoic Membrane (CAM), respectively. Eight
      days later, the implanted constructs were explanted, histologically processed and
      vascularization evaluated by means of a computer-assisted image analysis program.
      Matrices containing preadipocytes displayed a significantly higher density of
      vascularization, whereas in the control group (fibrin without preadipocytes) no
      vessel ingrowth was observed. Daily application of recombinant growth factors
      added to the medium did not positively influence vascularization of the implant.
      Our investigations demonstrate that preadipocytes possess a strong angiogenic
      potential to induce and support neovascularization of 3D-fibrin matrices under in
      vivo conditions. Addition of recombinant growth factors did not result in any
      stimulatory effect. Neither did the application of fibrin alone demonstrate an
      angiogenic potential with regard to induction of vascularization.

PMID- 16966140
TI  - One-stage completely laparoscopic restorative proctocolectomy for ulcerative
      colitis complicated with sigmoid colon cancer--a case report.
AB  - Recent advances in laparoscopic surgery have made it possible to perform
      restorative proctocolectomy (RP) for ulcerative colitis (UC) or familial
      adenomatous polyposis (FAC). However, most of these procedures are performed as
      two-stage operations with the creation of diverting ileostomy. Furthermore, they
      are performed with a small abdominal incision from 4 to 8 cm in length. We
      describe the first case of ulcerative colitis that underwent a single-stage
      completely laparoscopic restorative proctocolectomy without an abdominal
      incision. The patient also underwent lymph node dissection since he had a sigmoid
      colon cancer. The postoperative course was uneventful and the functional outcome
      was satisfactory. Considering the improved cosmetic as well as functional results
      achieved by this procedure, the present technology can be applied for selected
      patients, especially young UC or FAP patients needing RP who seek for a superior
      cosmetic result.

PMID- 16966141
TI  - Virulence factor profiles and antimicrobial susceptibilities of ocular bacillus
      isolates.
AB  - Bacillus causes one of the most rapidly blinding intraocular infections:
      endophthalmitis. In this study, Bacillus spp. were isolated from ocular infection
      cases, taxonomically characterized by riboprint analysis, and screened for the
      presence of putative virulence factors. The ability of these isolates to kill
      retinal and corneal cells was examined, as were antibiotic susceptibility
      profiles. The majority of isolates belonged to the B. cereus taxonomic group of
      microorganisms and were identified as B. cereus (53%) or B. thuringiensis (26%).
      Toxins were identified in most B. thuringiensis and B. cereus isolates. Most B.
      cereus and B. thuringiensis killed corneal and retinal cells within 6 h. All
      isolates were susceptible to most antibiotics tested, with quinolones and
      vancomycin being the most potent. These findings represent the first report of B.
      thuringiensis as an important ocular pathogen, demonstrates the potential ocular
      toxicity of B. cereus and B. thuringiensis isolates, and identifies antibiotics
      whose efficacy against Bacillus were superior to those used clinically.

PMID- 16966142
TI  - Apolipoprotein E modulates establishment of HSV-1 latency and survival in a mouse
      ocular model.
AB  - PURPOSE: To evaluate and compare the neuroinvasiveness and neurovirulence after
      ocular HSV-1 infection in ApoE knockout (ApoE-/-) and control C57BL/6 (ApoE+/+)
      mice. METHODS: Age-matched (14 weeks of age) C57BL/6J (ApoE+/+) female mice and
      female ApoE knockout (ApoE-/-) mice were inoculated by corneal scarification with
      HSV-1 strain 17Syn+. Analysis of HSV-1 replication in the mouse cornea was
      assessed through infectious virus assays of ocular (tear film) swabs at 1 to 5
      days postinoculation (PI), slit-lamp examination (SLE) of corneas at PI days 1 to
      7, and survival of infected mice. The contribution of apoE to the efficient
      establishment of latency was measured by real-time PCR quantitation of the latent
      viral genome in the trigeminal ganglia (TG) of infected mice. RESULTS: These
      studies showed that HSV-1 strain 17Syn+ replicates efficiently in the eyes,
      regardless of the host ApoE genotype. Neither the scoring of corneal pathology
      via SLE nor the infectious virus assay of the tear film resulted in any
      statistical differences between ApoE knockout (-/-) mice or the C57BL/6 (ApoE+/+)
      mice. In mice latently infected with HSV-1, our real-time PCR data showed
      significantly lower viral copy numbers of HSV-1 DNA in ApoE knockout (ApoE-/-)
      mice compared with C57BL/6 (ApoE+/+) mice. C57BL/6 (ApoE+/+) mice are more
      susceptible to the neurovirulence of HSV-1 strain 17Syn+ than female ApoE
      knockout (-/-) mice, as demonstrated by the fact that 50% (7/14) of the female
      C57BL/6 (ApoE+/+) mice inoculated with 17Syn+ died, as opposed to none (0/14) of
      the age- and sex-matched ApoE knockout mice. CONCLUSIONS: These data indicate
      that age (14 weeks) and sex-matched (female) wild mice with an ApoE null
      background (ApoE-/-) are more resistant and less efficient in the establishment
      of latency compared with ApoE+/+ mice in the C57BL/6 background.

PMID- 16966143
TI  - Immunohistochemical localization of EGF, TGF-alpha, TGF-beta, and their receptors
      in rat corneas during healing of excimer laser ablation.
AB  - PURPOSE: Members of the epidermal growth factor (EGF) and transforming growth
      factor beta (TGF-beta) families of growth factors and receptors are known to
      regulate key aspects of corneal wound healing, including epithelial migration and
      scar formation. To further understand their roles, mRNA levels were measured and
      proteins were immunolocalized in rat corneas at multiple time points during
      healing of excimer laser ablation injury. METHODS: Excimer laser photoablation
      was performed to a depth of 50 microm on rat corneas. Levels of mRNAs for EGF,
      TGF-alpha, TGF-beta isoforms 1, 2, and 3, and their receptors (EGF-R and TGFbeta
      IIR) were measured by quantitative RT-PCR on days 0, 1.5, 7, 21, 42, and 91 after
      ablation. Immunohistochemical localization of the growth factors and their
      receptors was performed on days 0, 7, and 21 in corneal sections. RESULTS: Levels
      of EGF mRNA remained stable in rat corneas after ablation (68 +/- 12 copies/cell,
      mean +/- SD), whereas levels of TGF-alpha mRNA progressively increased sixfold to
      a maximum at day 42 (300 copies/cell) then slightly decreased on day 91. Levels
      of EGF-R mRNA rapidly increased 60-fold on day 7 compared with day 0 (571 vs. 9
      copies/cell) then decreased sixfold above baseline at day 91. Levels of TGF-beta1
      mRNA remained stable (36 +/- 10 copies/cell), whereas levels of TGF-beta2 and TGF
      beta3 mRNAs peaked on day 21 (300-fold and 25-fold increase) and remained
      elevated through day 91. Levels of TGFbeta-IIR mRNA showed a similar pattern.
      Immunostaining of all the growth factors and receptors was primarily in basal
      layers of epithelial cells in uninjured cornea and during healing. Intensity of
      immunostaining for TGF-beta1, TGFbeta-IR, and TGFbeta-IIR increased appreciably
      in the basal epithelial layers after ablation. CONCLUSIONS: Levels of mRNAs for
      several key members of the EGF and TGF-beta systems increase during corneal wound
      healing. In addition, the proteins are primarily localized in basal layers of
      epithelial cells, which suggest these cells are active in synthesizing autocrine
      and paracrine growth factors that modulate corneal wound healing.

PMID- 16966144
TI  - Increased risk for herpetic eye disease in patients with allergic conjunctivitis.
AB  - PURPOSE: To evaluate the risk of ocular surface herpetic eye disease (osHED) in
      allergic eye disease. METHODS: We calculated the risk for osHED in 11,205
      patients on antiallergic ocular topical agents compared with 453,069 controls
      based on filled prescriptions for topical acyclovir between 2001 and 2003.
      RESULTS: Significantly more allergic patients, of all age groups, received
      treatment for osHED (p < 0.01). The age and gender adjusted relative risk for
      allergic patients to suffer an osHED event was 2.31 (95% CI: 1.84-2.90), raising
      to 3.55 (95% CI: 2.0-6.4) in patients that filled > or = 4 antiallergic
      prescriptions. CONCLUSIONS: Patients treated for allergic eye disease have an
      increased risk of osHED.

PMID- 16966145
TI  - Plasma endothelin-1 level in Japanese normal tension glaucoma patients.
AB  - PURPOSE: To compare the plasma concentration of endothelin-1 (ET-1) among
      patients < 60 years of age with normal-tension glaucoma (NTG), primary open-angle
      glaucoma (POAG), and in age-matched normal participants. METHODS: Plasma
      concentration of ET-1 was determined in 30 NTG 18 POAG patients, and 19 age
      matched normal participants using an enzyme immunoassay. RESULTS: The ET-1 level
      was 1.49 +/- 0.51 pg/ml in the NTG patients (49.4 +/- 8.8 years), 1.58 +/- 0.64
      pg/ml in the POAG patients (44.7 +/- 10.7 years), and 1.33 +/- 0.50 pg/ml in the
      normal participants (49.9 +/- 5.6 years). The ET-1 levels were not significantly
      different among the three groups, and no significant correlation with the extent
      of visual field damage, intraocular pressure (IOP), refraction, or age was seen
      in the glaucoma patients. CONCLUSIONS: The plasma ET-1 level showed no difference
      among NTG patients, POAG patients, and normal participants < 60 years of age in
      the Japanese population.

PMID- 16966146
TI  - Lens fluorescence in relation to glucose tolerance and genetic predisposition to
      type 2 diabetes mellitus in a population-based study.
AB  - PURPOSE: The fluorescence of the lens has the characteristics of a life-long
      cumulative index of glycemia, and it is elevated in patients with diabetes in
      proportion to the duration of diabetes and the level of glycemia. Consequently,
      lens fluorometry should be capable of providing an estimate of prediagnostic
      disease duration when patients are diagnosed with type 2 diabetes. Among
      euglycemic subjects, first-degree relatives of patients with type 2 diabetes tend
      to have higher glycemia levels than subjects who are unrelated to diabetes
      patients. They should therefore also have the higher lens fluorescence values.
      METHODS: The study comprised 218 Caucasian subjects in self-reported good health
      aged 30-88 years who were recruited from population-based studies to represent
      approximately equal proportions of different type 2 diabetes family history
      characteristics: no diabetic relative, first-degree offspring, second-degree
      offspring, not first-degree offspring but possibly second-degree offspring, or
      uncertain family history. Characterization of subjects included oral glucose
      tolerance testing and lens fluorometry. RESULTS: Type 2 diabetes was diagnosed in
      10 subjects (4.6% of the population) and impaired glucose tolerance in 12
      subjects (5.5%). Regression analysis indicated a prediagnostic duration of type 2
      diabetes of 2.7 years versus 0.1 years for impaired glucose tolerance. Neither
      group demonstrated significantly increased lens fluorescence compared with
      euglycemic subjects. Being a first-degree relative of a patient with type 2
      diabetes was associated with higher lens fluorescence than having no relative
      with diabetes (p = 0.02). CONCLUSIONS: Population screening by fasting blood
      glucose measurement can advance the diagnosis and initiation of treatment of type
      2 diabetes mellitus by nearly a decade, compared with previous studies of
      patients diagnosed in routine clinical practice. In addition to higher than
      normal glycemia, euglycemic subjects who are offspring of patients with type 2
      diabetes also have both elevated lens fluorescence and elevated glycemia. Fasting
      blood glucose measurement remains the method of choice for type 2 diabetes
      screening.

PMID- 16966147
TI  - Characterization of barrier properties and inducible VEGF expression of several
      types of retinal pigment epithelium in medium-term culture.
AB  - PURPOSE: To investigate and compare the characteristics of four different types
      of retinal pigment epithelium (RPE) cells cultured for 2 to 5 weeks to provide
      guidance when choosing RPE cells for experimentation. METHODS: Human cell lines
      ARPE-19 (ARPE) and D407, primary RPE cells from C57Bl/6 mouse (mRPE), and primary
      human fetal RPE (hfRPE) cells were grown in respective media previously reported
      to be optimal for each cell type. Two methods to obtain hfRPE were used: one
      isolated outside and transported to our laboratory, and one isolated primarily
      within our laboratory from donor human fetal eyes. Barrier function was
      determined by transepithelial electrical resistance (TER) and permeability and
      structure by localization of Na+,K+-ATPase alpha-1, ZO-1, and actin. VEGF
      expression, determined by real-time polymerase chain reaction (PCR) for mRNA and
      ELISA for protein, was determined after exposure to 24 h of 1% oxygen. Madin
      Darby canine kidney (MDCK) cells were compared as a non-RPE epithelial cell line.
      RESULTS: ARPE at passage 15, but not passage 32, maintained steady low TER
      measurements (up to 30 ohms x cm(2)) despite forming a monolayer with apical
      Na+,K+-ATPase alpha-1 labeling after 35 days. mRPE developed and maintained a TER
      of 30 ohms x cm(2) for 2 weeks but did not localize ATPase. hfRPE showed two
      phenotypes. hfRPE isolated remotely and sent to us appeared more mesenchymal and
      undifferentiated (hfRPE-U) and had a slow but steady increase in measured TER to
      approximately 25 ohms x cm(2), whereas hfRPE isolated from donor eyes in our
      laboratory showed well-differentiated monolayers (hfRPE-D) with TER measurements
      > 500 ohms x cm(2) within 1 month of culture. TER measurements reflected
      permeability determined by the measurement of paracellular movement of sodium
      fluorescein. All human RPE cell types showed expression of VEGF mRNA and protein,
      and expression was upregulated by hypoxia in hfRPE and D407, but not in ARPE,
      which had constitutively high expression. ARPE expressed high levels of VEGF
      protein in media and cell lysates (777.2; 54.4 pg/mg protein, respectively),
      whereas hfRPE and D407 produced significantly less (media: 5.7 [p = 0.001], 323.6
      pg/mg protein [p = 0.01]; lysate: 0 [p < 0.001], 3.5 pg/mg protein [p < 0.001],
      respectively). CONCLUSIONS: Primary RPE cells and those from cell lines had
      different responses to medium-term culture or hypoxic stress. Primary isolation
      of hfRPE cells with careful control of culture conditions to assure adequate
      differentiation is recommended when using this cell as an example of a highly
      polarized epithelium. For disease, use of RPE cells that do not require long-term
      culture are more efficient and may be more relevant to study certain pathologies.

PMID- 16966148
TI  - An ultrastructural study of the pathology of the retinal pigment epithelium,
      Bruch's membrane, and the choriocapillaris in the aged Fischer 344 rat.
AB  - PURPOSE: The neural retinal degeneration in the aging Fischer 344 (F344) rat has
      been previously characterized. Here we describe the ultrastructural changes that
      occur in the retinal pigment epithelium (RPE), Bruch's membrane, and
      choriocapillaris in the periphery of the aged Fischer 344 rat. METHODS: F344 eyes
      from 24-month-old animals (n = 4 animals, 8 eyes) were fixed and embedded for
      ultrastructural study. Serial mid-sagittal sections were taken from the superior
      peripheral retinas within 300 microm of the ora serrata. Pathology within the
      RPE, Bruch's membrane, and choriocapillaris was described. RESULTS: Progressive
      changes were seen in the RPE/Bruch's/choriocapillaris complex, increasing
      anteriorly as the ora serrata was approached. Early pathology of the RPE included
      increased number of basal infoldings, increased number of phagolysosomes and
      lipofuscin deposits, attenuation, inclusion of vasculature, vesicle formation,
      and whirling extensions of the basement membrane into the cytoplasm. Bruch's
      membrane showed spots of considerable thinning, but most prominent was the
      nodular thickening. The choriocapillaris was found to have severe endothelial
      degeneration and transformation to fibrous tissue in the most severely affected
      regions. Lipofuscin was also found in areas of degenerated choriocapillaris.
      CONCLUSIONS: Prior work focused on the neural retina, documented photoreceptor
      cell loss, and showed that Muller cell changes preceded that loss in the
      periphery of the F344 rat. It is now evident that the pathology in the
      RPE/Bruch's membrane/choriocapillaris complex may also be a critical component of
      the overall degenerative process. A possible mechanism for the extensive
      peripheral retinal degeneration in the F344 is presented.

PMID- 16966149
TI  - Photodynamic therapy of experimental choroidal neovascularization in the mouse.
AB  - PURPOSE: To evaluate the qualitative and quantitative effects of verteporfin
      photodynamic therapy (PDT) on laser-induced choroidal neovascularization (CNV) in
      the mouse. METHODS: PDT was applied to the normal mouse fundus using light doses
      of 32, 64, and 83 s, and histological analysis of the treated areas was
      performed. CNV was induced using krypton laser photocoagulation of the fundus,
      and the CNV lesions were subsequently treated with PDT using light doses of 32,
      64, and 83 s. Enucleated eyes were analyzed with light and transmission electron
      microscopies, and measurements of CNV size were done on histologic sections and
      on isolectin B4-stained choroidal flat mounts. RESULTS: PDT induced a light dose
      dependent damage to the surrounding neural retina in normal eyes. At a light dose
      of 32 s, minimal damage was detected in the neural retina, whereas higher light
      doses caused distortion and disruption of the outer and inner nuclear layers and
      of the retinal pigment epithelium. When PDT was applied over laser-induced CNV
      lesions, the relative height of the lesions was significantly reduced (p < 0.05)
      using all light doses. Transmission electron microscopy 1 day after PDT treatment
      revealed occlusion of many of the CNV vessels. One week after PDT treatment, the
      CNV lesions contained patent vessels irrespective of light dose applied.
      Accordingly, PDT treatment inhibited (p < 0.05) but did not halt CNV lesion
      growth. CONCLUSIONS: PDT treatment of laser-induced CNV may create an acute
      occlusion of neovessels and an inhibition of CNV lesion growth without apparent
      injury to the surrounding neural retina. However, PDT-treated areas will remain
      vascularized with continued growth of the CNV lesion, which in turn may explain
      the often limited effect of PDT in patients with neovascular age-related macular
      degeneration. Elevating the PDT light dose will not increase the treatment effect
      substantially but may lead to increased collateral injury.

PMID- 16966152
TI  - Diagnostic value of voice acoustic analysis in assessment of occupational voice
      pathologies in teachers.
AB  - It has been shown that teachers are at risk of developing occupational dysphonia,
      which accounts for over 25% of all occupational diseases diagnosed in Poland. The
      most frequently used method of diagnosing voice diseases is videostroboscopy.
      However, to facilitate objective evaluation of voice efficiency as well as
      medical certification of occupational voice disorders, it is crucial to implement
      quantitative methods of voice assessment, particularly voice acoustic analysis.
      The aim of the study was to assess the results of acoustic analysis in 66 female
      teachers (aged 40-64 years), including 35 subjects with occupational voice
      pathologies (e.g., vocal nodules) and 31 subjects with functional dysphonia. The
      acoustic analysis was performed using the IRIS software, before and after a 30
      minute vocal loading test. All participants were subjected also to laryngological
      and videostroboscopic examinations. After the vocal effort, the acoustic
      parameters displayed statistically significant abnormalities, mostly lowered
      fundamental frequency (Fo) and incorrect values of shimmer and noise to harmonic
      ratio. To conclude, quantitative voice acoustic analysis using the IRIS software
      seems to be an effective complement to voice examinations, which is particularly
      helpful in diagnosing occupational dysphonia.

PMID- 16966150
TI  - Angiogenic profile of uveal melanoma.
AB  - Uveal melanoma develops in one of the most capillary-rich tissues of the body and
      is disseminated hematogenously. Knowledge of the nature and the spatiotemporal
      expression of angiogenic factors in uveal melanoma is essential to the
      development of new treatment strategies, especially with regard to improving
      survival. In this study, we measured the angiogenic potential of several
      angiogenic factors in different uveal melanoma cell lines, in an in vivo model,
      and in primary tumor material from patients with melanoma. Most uveal melanoma
      cell lines expressed vascular endothelial growth factor (VEGF)-A (isoforms 121,
      165, 189), VEGF-B, VEGF-C, VEGF-D, and basic fibroblastic growth factor (b-FGF)
      to various extents. The expression of VEGF-A 121 was always higher than that of
      the other VEGF-A isoforms, suggesting that VEGF-A 121 is the most abundant VEGF-A
      isoform. All experimentally induced tumors expressed VEGF-A, VEGF-B, VEGF-C, VEGF
      D, and basic fibroblastic growth factor (b-FGF). Similarly, significant amounts
      of mRNA for VEGF-B, VEGF-C, VEGF-D, and b-FGF were detected in uveal melanoma
      material from patients. In contrast, VEGF-A mRNA (121, 165, 189) was low (9/28)
      or not detectable in the tumor samples. The synthesis of VEGF-A 165 and b-FGF
      protein by various cell lines was measured by enzyme-linked immunosorbent assay
      (ELISA). Most uveal melanoma cell lines, but not normal melanocytes, strongly
      synthesized and secreted VEGF-A 165 and b-FGF during cell culture. Our data
      suggest that the expression of (lymph) angiogenic factors may play a causal role
      in the angiogenesis and progression of uveal melanoma and distant metastasis.

PMID- 16966153
TI  - Perceptual and acoustic evidence of speaker adaptation to a thin pseudopalate.
AB  - The purpose of this study was to examine the effect of a thin pseudopalate on the
      speech of normal adults. It was hypothesized that speech would be initially
      altered, but speakers would adapt quickly to the device. Eleven speakers produced
      words without the pseudopalate and at six intervals with the appliance in place.
      Consonant acoustics were changed initially, but returned to baseline within
      approximately 30 minutes. Perceptually, consonant identification and distortion
      ratings were unchanged when wearing the pseudopalate. Results suggest an initial
      alteration to speech detectable acoustically, but rapid adaptation, for most
      speakers. Investigators using thin pseudopalates must recognize that speech is
      altered, at least initially, and account for this in their procedures and
      interpretation of results.

PMID- 16966154
TI  - Computational modelling of effect of tonsillectomy on voice production.
AB  - The aim of this study is to develop mathematical 3D finite element (FE) models
      for numerical simulations of vibroacoustic properties of the human vocal tract
      after a tonsillectomy. Similar experimental studies are not easily realizable on
      living subjects. The FE models of the acoustic spaces corresponding to the human
      vocal tract for the Czech vowels /a:/ and /i:/ and the acoustic space around the
      human head were used in numerical simulations of phonation. The acoustic resonant
      characteristics of the FE models were studied using modal and transient analyses
      (excitation by a short pulse). Calculated results show that a tonsillectomy
      causes a frequency shift of the 3rd (down by approximately 180 Hz) and 4th (down
      by approximately 120 Hz) formants down to the lower frequencies for the vowel
      /a:/ and similarly for the 2nd, 4th and 5th formants for the vowel /i:/ (all down
      by approximately 100 Hz). Similar effects and results can be found in
      experimental studies in literature. The formant changes are dependent on the size
      of additional acoustic spaces that occur after a tonsillectomy. The verification
      of the model was performed on the recordings of patients before and after the
      tonsillectomy operation. Multi-Dimensional Voice Program (MDVP Advanced, KAY
      Elemetrics Corp.) was used for the comparing of the formant centre frequencies.
      Very small differences in the results of subjective evaluation of the voice
      before and after tonsillectomy were found.

PMID- 16966155
TI  - A comparison of different methods to measure the EGG contact quotient.
AB  - The results from six published electroglottographic (EGG-based) methods for
      calculating the EGG contact quotient (CQEGG) were compared to closed quotients
      derived from simultaneous videokymographic imaging (CQKYM). Two trained male
      singers phonated in falsetto and in chest register, with two degrees of adduction
      in both registers. The maximum difference between methods in the CQEGG was 0.3
      (out of 1.0). The CQEGG was generally lower than the CQKYM. Within subjects, the
      CQEGG co-varied with the CQkym, but with changing offsets depending on method.
      The CQEGG cannot be calculated for falsetto phonation with little adduction,
      since there is no complete glottal closure. Basic criterion-level methods with
      thresholds of 0.2 or 0.25 gave the best match to the CQKYM data. The results
      suggest that contacting and de-contacting in the EGG might not refer to the same
      physical events as do the beginning and cessation of airflow.

PMID- 16966156
TI  - Investigation of voice initiation and voice offset characteristics with high
      speed digital imaging.
AB  - This study involves preliminary investigation of the characteristics of the voice
      initiation period (VIP) and voice offset period (VOP) using high-speed digital
      imaging. The goals of the study were to develop a methodology to objectively
      analyze these periods of phonation and to explore the feasibility of studying the
      effects of aging on these phonation segments. Results of the analysis of the data
      from two female subjects, one younger and one older, with the developed
      methodology, demonstrated that the older subject's VIP was characterized by a
      slow and irregular increase in glottal area waveform (GAW) until reaching 90% of
      the maximum opening of the glottis at 244 frames or 122 ms. The younger subject
      demonstrated a sharp increase in GAW during VIP, taking only 155 frames or 77.5
      ms to reach the 90% mark. Also, the older subject took a greater number of frames
      for the vocal fold vibration to come to a complete stop than the younger subject
      during the VOP; 275 frames and 150 frames respectively.

PMID- 16966157
TI  - Biomarkers in cancer screening, research and detection: present and future: a
      review.
AB  - Biomarkers provide a powerful and dynamic approach to understanding the spectrum
      of malignancies with applications in observational and analytic epidemiology,
      randomized clinical trials, screening, diagnosis and prognosis. Defined as
      alterations in the constituents of tissues or body fluids, these markers offer a
      means for homogeneous classification of a disease and risk factor, and they can
      extend one's basic information about the underlying pathogenesis of disease. The
      goals in cancer research include finding biomarkers that can be used for the
      early detection of cancers, design individual therapies, and to identify
      underlying processes involved in the disease. Because so many myriad processes
      are involved in the diseased states, the goal is similar to 'finding a needle in
      a haystack'. However, the development of many -omic technologies, such as
      genomics and proteomics, has allowed us to monitor a large number of key cellular
      pathways simultaneously. This has enabled the identification of biomarkers and
      signalling molecules associated with cell growth, cell death and cellular
      metabolism. These are also facilitating in monitoring the functional disturbance,
      molecular and cellular damage, and damage response. This brief review describes
      the development of biomarkers in cancer research and detection with emphasis on
      different proteomic tools for the identification and discovery of new biomarkers,
      different clinical assays to detect various biomarkers in different specimens,
      role of biomarkers in cancer screening and last but not the least, the challenges
      in this direction of cancer research.

PMID- 16966158
TI  - Application of proteomic strategies to the identification of urinary biomarkers
      for prostate cancer: a review.
AB  - In the post-genomic era, genes and proteins are now studied on a more
      comprehensive scale. Studying disease processes at only the genetic or
      transcriptomic level will give an incomplete amount of information. A proteomic
      approach potentially allows for a more global overview of how disease processes
      affect the proteins present in cells, tissues and organisms. The challenge arises
      in determining which proteins are affected in specific diseases and establishing
      which of these changes are unique to a particular disease. Existing and emerging
      proteomic technologies allow for high throughput analysis of proteins in a
      variety of sample types. Prostate cancer is a significant male health problem in
      the Western world. It is widely accepted that more specific prognostic and
      diagnostic markers of prostate cancer are urgently required. The present paper
      suggests that urine may be an attractive biofluid in which to pursue the
      identification of novel biomarkers of prostate cancer. This review introduces
      some proteomic techniques including mass spectrometry and the newer, quantitative
      proteomic strategies. It focuses on the potential application of these platforms
      to novel urinary biomarker identification in prostate malignancy. It also
      includes a synopsis of the current literature on urinary proteomics.

PMID- 16966159
TI  - Comparison of the urinary excretion time courses of pyrene-1,6-dione, pyrene-1,8
      dione and 1-hydroxypyrene in rats intravenously exposed to pyrene.
AB  - The urinary excretion time courses of pyrene-1,6-dione (P16D), pyrene-1,8-dione
      (P18D) and 1-hydroxypyrene (1-OHP) were compared in Sprague-Dawley and Wistar
      rats. Groups of five male rats, of about 200 g of body weight, were injected
      intravenously with 0.05, 0.5, 5 and 50 micromol pyrene kg-1 of body weight. Urine
      was collected at 2, 4, 6, 8, 10, 12, 18, 24, 30, 42 and 48 h post-dosing. Pyrene
      metabolites were measured by high-performance liquid chromatography
      (HPLC)/fluorescence after enzymatic hydrolysis of the glucurono- and sulfo
      conjugates, extraction on Sep-Pak C18 cartridges and, for the analysis of dione
      metabolites, derivatization to stable diacetoxypyrene molecules. Over the 48-h
      sampling period, on average 17.4-25.6% of the injected pyrene was excreted
      overall as P16D, 6.4-8.8% as P18D and 0.6-0.8% as 1-OHP in the urine of Sprague
      Dawley rats. By comparison, on average 10.3-14.7% of the intravenous pyrene dose
      was recovered as P16D, 4.8-6.4% as P18D and 0.3-0.4% as 1-OHP in the urine of
      Wistar rats. In both strains of rats there was no clear effect of the dose on the
      0-48-h cumulative urinary excretion of P18D and 1-OHP over the entire dose range,
      while the percentage of dose recovered overall as P16D in urine at the highest
      dose (50 micromol kg-1) was statistically lower than at the other doses. The 0-48
      h cumulative percentage of pyrene dose excreted as metabolites in the urine of
      Sprague-Dawley rats was also significantly higher than in Wistar rats (p<0.01)
      exposed under identical conditions. As for the urinary excretion-time courses of
      the different metabolites, for a given dose and strain of rats, excretion curves
      of P16D, P18D and 1-OHP generally evolved in parallel. There was also no clear
      effect of the dose on the excretion rate, thus half-life, of pyrene metabolites,
      except for P16D in Sprague-Dawley rats at the highest dose where elimination
      tended to be slower compared with the other doses (p<0.01). The average first
      order elimination half-life of P16D, P18D and 1-OHP was 4.0, 5.7 and 4.1 h,
      respectively, in Sprague-Dawley rats, and 5.1, 6.1 and 5.1 h, respectively, in
      Wistar rats (all doses combined but excluding the highest dose for P16D). This
      study showed the relative importance of metabolic pathways leading to diones
      compared with 1-OHP. These dioxygenated metabolites appear to be interesting
      biomarkers of pyrene exposure at environmentally and occupationally relevant
      doses. Their adequacy as biomarkers of human exposure has yet to be confirmed.

PMID- 16966160
TI  - Integrated use of biomarkers and bioaccumulation data in Zebra mussel (Dreissena
      polymorpha) for site-specific quality assessment.
AB  - One of the useful biological tools for environmental management is the
      measurement of biomarkers whose changes are related to the exposure to chemicals
      or environmental stress. Since these responses might vary with different
      contaminants or depending on the pollutant concentration reached in the organism,
      the support of bioaccumulation data is needed to prevent false conclusions. In
      this study, several persistent organic pollutants -- 23 polychlorinated biphenyl
      (PCB) congeners, 11 polycyclic aromatic hydrocarbons (PAHs), six
      dichlorodiphenyltricholroethane (DDT) relatives, hexachlorobenzene (HCB),
      chlorpyrifos and its oxidized metabolite -- and some herbicides (lindane and the
      isomers alpha, beta, delta; terbutilazine; alachlor; metolachlor) were measured
      in the soft tissues of the freshwater mollusc Zebra mussel (Dreissena polymorpha)
      from 25 sampling sites in the Italian portions of the sub-alpine great lakes
      along with the measure of ethoxyresorufin dealkylation (EROD) and
      acetylcholinesterase (AChE) activity. The linkage between bioaccumulation and
      biomarker data allowed us to create site-specific environmental quality indexes
      towards man-made chemicals. This classification highlighted three different
      degrees of xenobiotic contamination of the Italian sub-alpine great lakes: a high
      water quality in Lake Lugano with negligible pollutant levels and no effects on
      enzyme activities, an homogeneous poor quality for Lakes Garda, Iseo and Como,
      and the presence of some xenobiotic point-sources in Lake Maggiore, whose
      ecological status could be jeopardized, also due to the heavy DDT contamination
      revealed since 1996.

PMID- 16966161
TI  - High-performance liquid chromatography (HPLC) determination of inosine, a
      potential biomarker for initial cardiac ischaemia, using isolated mouse hearts.
AB  - Each year in the USA approximately 7-8 million patients with non-traumatic chest
      pain come to hospital emergency rooms. It is estimated that approximately 2-5% of
      these patients are experiencing cardiac ischaemia, but due to the shortcomings of
      the available testing methods they are incorrectly diagnosed and discharged
      without appropriate therapy having been provided. Preliminary data with a
      globally ischaemic mouse heart model has demonstrated that endogenous inosine
      might be a potential biomarker of initial cardiac ischaemia before cardiac tissue
      necrosis. A high-performance liquid chromatographic diode array detection (HPLC
      DAD) method was utilized for the detection and quantification of inosine in Krebs
      Henseleit (Krebs) buffer solution perfusing from surgically removed and isolated
      mouse hearts undergoing global cardiac ischaemia. A C18 column at a flow rate of
      0.6 ml min-1 with an aqueous mobile phase of trifluoroacetic acid (0.05%
      trifluoroacetic acid in deionized water, pH 2.2, v/v) and methanol gradient was
      used for component separation. The assay detection limit for inosine in Krebs
      buffer solution was 500 ng ml-1 using a 100-microl neat injection. The HPLC
      results were used to determine total cardiac effluxed inosine into the Krebs
      effluent for each mouse during oxidative stress and compared with the per cent
      cardiac ventricular functional recovery rate to determine if a relationship
      exists amongst this cardiovascular parameter during periods of cardiac oxidative
      stress.

PMID- 16966162
TI  - Whole blood glutathione peroxidase and erythrocyte superoxide dismutase
      activities, serum trace elements (Se, Cu, Zn) and cardiovascular risk factors in
      subjects from the city of Ponta Delgada, Island of San Miguel, The Azores
      Archipelago, Portugal.
AB  - Activities of whole blood glutathione peroxidase (GSH-Px) and erythrocyte
      superoxide dismutase (SOD) and serum levels of selenium (Se), copper (Cu) and
      zinc (Zn) were measured in 118 apparently healthy subjects aged 20-60 years from
      the city of Ponta Delgada, Island of San Miguel, The Azores Archipelago,
      Portugal. Data were analysed by age/gender, lipid profile and blood pressure as
      cardiovascular risk factors searching for their relevance when assessing
      reference values for antioxidant biomarkers. GSH-Px was in the same range, but
      SOD was significantly lower than in other Portuguese populations. Neither
      activity differed with gender. GSH-Px activity increased with age, namely in
      normolipidemic men versus the hyperlipidemic group in which a decrease was
      observed. This suggests a progressive impairment of GSH-Px with age caused by an
      enhanced production of oxidant species in hyperlipidemia. GSH-Px was 30% lower in
      male hypertensives versus normotensives. SOD activity did not relate to age or
      blood pressure but was 17% higher in the hyperlipidemic men versus the
      normolipidemic group, suggesting a better antioxidant protection by SOD than by
      GSH-Px in hyperlipidemia and hypertension. Se was higher in men versus women,
      particularly in the older subjects, and partly related to hyperlipidemia. Zn
      levels showed a similar dependency on gender, not related to age or lipid
      profile. Cu levels were much higher in women than in men in all age or lipid
      profile classes and decreased in hyperlipidemia. They were lowered with age in
      both genders, particularly in normolipidemic women. The present research
      therefore suggests that hyperlipidemia and hypertension do affect antioxidant
      status and should be considered when assessing antioxidant biomarkers in blood.

PMID- 16966163
TI  - Quantitation of DNA in buccal cell samples collected in epidemiological studies.
AB  - Buccal cell samples are increasingly used in epidemiological studies as a source
      of genomic DNA. The accurate and precise quantitation of human DNA is critical
      for the optimal use of these samples. However, it is complicated by the presence
      of bacterial DNA and wide inter-individual variation in DNA concentration from
      buccal cell collections. The paper evaluated the use of ultraviolet light (UV)
      spectroscopy, Hoechst (H33258) and PicoGreen as measures of total DNA, and real
      time quantitative polymerase chain reaction (PCR) as a measure of human
      amplifiable DNA in buccal samples. Using serially diluted white blood cell DNA
      samples (at a concentration range of 300 to 0.5 ng microl-1), UV spectroscopy
      showed the largest bias, followed by Hoechst, especially for low concentrations.
      PicoGreen and real-time PCR provided the most accurate and precise estimates
      across the range of concentrations evaluated, although an increase in bias with
      decreasing concentrations was observed. The ratio of real-time PCR to PicoGreen
      provided a reasonable estimate of the percentage of human DNA in samples
      containing known mixtures of human and bacterial DNA. Quantification of buccal
      DNA from samples collected in a breast cancer case-control study by PicoGreen and
      real-time PCR indicated that cytobrush and mouthwash DNA samples contain similar
      percentages of human amplifiable DNA. Real-time PCR is recommended for the
      quantification of buccal cell DNA in epidemiological studies since it provides
      precise estimates of human amplifiable DNA across the wide range of DNA
      concentrations commonly observed in buccal cell DNA samples.

PMID- 16966164
TI  - Acridinium ester conjugated to lectin as chemiluminescent histochemistry marker.
AB  - Cell differentiation/dedifferentiation includes changes in oligosaccharide
      composition and distribution in the cell surface glycoconjugates. Lectins have
      been used as auxiliary tools in histopathological diagnosis of mammary, uterus
      and brain pathologies. Acridinium ester (AE) conjugated to biomolecules has been
      employed in chemiluminescent analytical applications. This work aimed to use a
      lectin, concanavalin A (Con A), conjugated to AE as a chemiluminescent
      histochemistry tool. Biopsies of normal and infiltrating duct carcinoma (IDC) of
      mammary tissues were treated by a Con A-AE derivative. Photon emission, observed
      during the breakage of the chemical bound between Con A and AE, was quantified,
      expressed in relative light units (RLU) and correlated to the labelling of the
      normal and transformed tissues. The results demonstrated that RLU presented a
      linear relationship with the labelled tissue area in the range 0.125-1.0 cm2
      (r=0.98). Furthermore, RLU was much higher for the IDC (1283.920x103+/
      220.621x103) than the normal tissue (2.565x103+/-0.247x103), namely, about 500
      times higher. The Con A-AE conjugation efficiency, differential staining of
      normal and IDC tissues, and quantification of results contribute to a decrease in
      the subjectivity in routine histopathological diagnoses and indicate that
      acrydinum ester can join other lectin marker to be used in histochemistry.

PMID- 16966165
TI  - Role of birds of prey as carriers and spreaders of Cryptococcus neoformans and
      other zoonotic yeasts.
AB  - In the last 20 years, cases of human cryptococcosis, have increased in
      immunocompromised patients. In several instances, the cases have been associated
      with the exposure of the patients to bird droppings. In order to investigate
      birds of prey as potential carriers and spreaders of Cryptococcus neoformans and
      other yeasts of importance in human infections, 182 swab samples were collected
      from the cloacae of several species of birds of prey (Group I) and 32 faecal
      samples from aviaries in which the birds were housed (Group II). Samples were
      also taken from digestive tract of 60 dead birds (Group III). A total of 454
      samples were cultured from which 215 colonies of yeastlike fungi were recovered
      and identified. Cryptococcusneoformans var. grubii was isolated from three
      cloacae samples (4.8%) collected from Falco tinnunculus and from one sample
      (3.1%) obtained from Buteo buteo, as well as from samples collected at the
      aviaries in which these birds were kept. Overall, 18 samples (9.9%) from Group I,
      13 (40.6%) from Group II, 12 crops (20%), three proventriculi (5%) and 12 cloacae
      (20%) from Group III yielded positive cultures for yeasts. The results indicate
      that birds of prey and in particular, F. tinnunculus and B. buteo, may act as
      carriers and spreaders of C. neoformans and other zoonotic yeasts.

PMID- 16966166
TI  - Heat killed cells of Cryptococcus neoformans var. grubii induces protective
      immunity in rats: immunological and histopathological parameters.
AB  - Different clinical parameters which included cell-mediated immune (CMI) response,
      were evaluated in a model of disseminated cryptococcosis in rats. The
      experimental animals were pretreated four days prior to their exposure to
      Cryptococcus neoformans var. grubii with either heat killed cells of this
      yeastlike pathogen (HKC) or capsular polysaccharide (CPS) emulsified in complete
      Freund adjuvant (CFA). Rats treated with HKC-CFA and intraperitoneally infected
      with C. neoformans var. grubii had significantly better clearance of yeasts from
      tissues, a lower concentration of the cryptococcal capsular polysaccharide,
      glucuronoxylomannan (GXM), in serum and tissues, and better histopathological
      parameters compared to unpretreated infected rats. In contrast, rats treated with
      CPS-CFA presented an exacerbation of infection with a significantly higher fungal
      burden in tissues, a higher concentration of GXM in serum, and worse
      histopathological parameters compared to similar unpretreated infected rats. In
      addition, HKC-CFA treatment produced a T helper 1 (Th1) profile with improvements
      in the spleen cell proliferative response, in the level of INFgamma production by
      CD4 T cells, and in the nitric oxide (NO) production by peritoneal cells. On the
      other hand, rats treated with CPS-CFA showed an increased level of the
      immunoregulatory cytokine IL10 production by CD4 T cells, but no modification in
      the NO production by peritoneal cells.

PMID- 16966167
TI  - Cytokine production in lungs and adrenal glands of high and low antibody
      producing mice infected with Paracoccidioides brasiliensis.
AB  - Mice genetically selected for high (H) and low (L) antibody production (HIV-A and
      LIV-A) were used in an experimental model of paracoccidioidomycosis. In a
      previous work, it was observed that male HIV-A animals were more susceptible to
      the infection due to adrenal gland damage. Male HIV-A and LIV-A animals were
      intravenously inoculated with Paracoccidioides brasiliensis (strain 18) and
      sacrificed 2, 4, 6, 8 and 10 weeks after inoculation. At each time interval,
      lungs and adrenals were removed to estimate recoverability of the fungus, as well
      as to determine Th1 (IFN-gamma, TNF-alpha) and Th2 (IL-4 and IL-10) cytokine
      profiles. While viable fungi recoverability from the lungs of HIV-A mice was
      higher after 4 and 8 weeks, there was less fungal recovery from the adrenals of
      LIV-A animals after the 2nd week, with total fungal elimination after the 8th
      week. With regard to Th2 cytokines, there was an inhibition in IL-4 production in
      the organs from infected animals, the extent of which varied according to the
      organ and the time period after initiation of infection. IL-10 production was
      found to be lower in both organs. Determination of Th1 cytokines revealed that
      IFN-gamma production increased in both organs, mainly in the adrenal of LIV-A
      after 8 and 10 weeks, when these animals showed a total fungal elimination. A
      significant difference was observed between HIV-A and LIV-A concerning TNF-alpha
      production in both organs and at all recovery times, in that LIV-A produced a
      higher level of this cytokine, mainly in the adrenal. These results may explain
      the high susceptibility of HIV-A to P. brasiliensis infection, is due, at least
      in part, to adrenal involvement. The higher production of Th1 cytokines by LIV-A
      in comparison to HIV-A mice may account for LIV-A resistance to P. brasiliensis
      infection. Our data reveal the importance of this experimental model in the study
      of the adrenal involvement in paracoccidioidomycosis, since this gland may be
      highly compromised in the patients, leading to the development of Addison's
      Disease.

PMID- 16966168
TI  - A Rhizopus oryzae strain isolated from resected bone and soft tissue specimens
      from a sinonasal and palatal mucormycosis case. Report of a case and in vitro
      experiments of yeastlike cell development.
AB  - We report a histologically and mycologically proven sinonasal mucormycosis case
      causing palatal necrosis in a nondiabetic patient with renal failure. Mycological
      examination of Giemsa stained imprinted tissue preparations revealed abundant
      yeast-like cells besides the typical mucoraceous hyphae. The fungus was isolated
      from surgical specimens and identified as Rhizopus oryzae by phenotypic and
      genotypic tests. Laboratory studies were performed to investigate the association
      of the yeast-like cells observed in tissue specimens and the fungus recovered in
      culture. In vitro induced yeast-like cell development of the case isolate was
      found under certain growth conditions and documented by photomicrographs.

PMID- 16966169
TI  - Blastomycosis in a South Indian patient after visiting an endemic area in USA.
AB  - We describe a case of blastomycosis in a diabetic patient from South India who
      had visited Milwaukee, Wisconsin, an endemic area for blastomycosis in the USA.
      After his return to Bangalore, India, the patient developed intermittent fever of
      moderate to high grade, cough, loss of weight and appetite, and abscesses in the
      left cubital fossa and thigh regions. Systemic examination at our hospital
      revealed that he had dullness to percussion over the chest region and decreased
      breath sounds. Direct examination of Gram-stained smears of the pus from an
      abscess showed many broad-based budding yeast cells and culture yielded a
      dimorphic fungus later identified as Blastomyces dermatitidis. Histologic
      examination of the curettage tissue slides stained with hematoxylin and eosin,
      periodic acid Schiff's reagent, and Gomori's methenamine silver stain procedures
      showed many broad-based budding cells characteristic of B. dermatitidis. The
      patient was successfully treated, initially with amphotericin B, followed by oral
      itraconazole for a period of 6 months. Blastomycosis cases in India are reviewed
      and the likely source of infection in this patient is discussed.

PMID- 16966170
TI  - Fulminating fungal sinusitis caused by Valsa sordida, a plant pathogen, in a
      patient immunocompromised by acute myeloid leukemia.
AB  - We describe a case in which a patient immunocompromised by acute myeloid leukemia
      experienced acute fulminating invasive fungal sinusitis followed by pneumonia and
      then death. Though the microbiology of the pneumonia could not be directly
      investigated, nasal lesions revealed fungal mycelium. Valsa sordida was
      consistently cultured from a biopsied sample. The fungus was identified to the
      genus level based on morphology in culture and DNA sequence homology, and then
      was placed at species level by means of phylogenetic analysis of the nuclear
      ribosomal internal transcribed spacer region. The fungus is in the order
      Diaporthales, family Valsaceae in the Ascomycota and is distributed worldwide as
      a pathogen of trees in the genera Populus and Salix. Koch's postulates were
      demonstrated to apply in a neutropenic rat model. The fungus was susceptible to
      antifungals with MIC-0 scores of 0.0313 microg/ml for amphotericin B, 0.25
      microg/ml for voriconazole, 0.0313 microg/ml for caspofungin, and MIC-2 of 16
      microg/ml for fluconazole. This is the first substantiated report of an isolate
      in the genus Valsa (anamorph Cytospora) being identified in human disease.

PMID- 16966171
TI  - A case of subcutaneous phaeohyphomycosis caused by Chaetomium globosum and the
      sequences analysis of C. globosum.
AB  - A 14-year-old boy developed painful erythema and necrosis on his face with
      petechia on his upper extremities. Microscopically, necrotic tissue treated with
      potassium hydroxide showed branched, dematiaceous, septate hyphae. Chaetomium
      globosum was isolated repeatedly from the necrotic tissues. Morphology and
      thermotolerance test of the pathogen were also studied. The internal transcribed
      spacer region in rRNA gene was amplified and sequenced. The sequence of this
      patient matched well with that of C. globosum in GenBank and from other patients
      and environment.

PMID- 16966172
TI  - Gangrenous necrosis of the diabetic foot caused by Fusarium acutatum.
AB  - Foot infections are common and serious complications of diabetic patients. We
      report the case of a 68-year-old patient with a diabetic foot infection that
      developed into a gangrenous necrosis. Fusarium spp. was isolated on two
      successive occasions with no other associated microorganisms. Histopathology
      demonstrated invasion of the fungus into the tisssue. These findings suggested an
      infection rather than colonization. A detailed morphological study showed that
      the isolate was Fusarium acutatum, which was confirmed by rDNA sequencing. This
      fungus is found only in Asia and has not been previously reported as a human
      pathogen.

PMID- 16966173
TI  - Sub-cutaneous phaeohyphomycosis caused by Cladophialophora devriesii in a United
      Kingdom resident.
AB  - An 83-year-old diabetic man receiving corticosteroids developed a forearm lesion.
      Histology confirmed the presence of a dematiaceous fungus, with associated
      granulomatous inflammation. Culture of a biopsy yielded fungal colonies with
      branching chains of single-celled, melanised, dry, sympodial conidia, which were
      identified as Cladophialophora devriesii on the basis of morphology and rDNA gene
      sequencing. To date, C. devriesii has been a relatively rare cause of human
      disease. To our knowledge, this is only the second case to be described, and the
      first report of infection in a UK resident.

PMID- 16966174
TI  - Fatal hemoptysis from invasive Aspergillus niger in a patient with cavitary lung
      disease and Mycobacterium avium complex infection.
AB  - Invasive aspergillosis typically afflicts immunocompromised patients, whereas
      pulmonary aspergilloma is a recognized complication of pre-existing cavitary lung
      disease in immunocompetent hosts. In both cases, the most prevalent pathogens are
      Aspergillus fumigatus and Aspergillus flavus. We describe a case of fatal
      hemoptysis from invasive Aspergillus niger infection in the setting of bullous
      lung disease, steroid-treated sarcoidosis, and Mycobacterium avium complex
      infection. This report highlights the potential for A. niger to cause invasive
      disease in conjunction with other pathologic processes in the lung.

PMID- 16966175
TI  - Recrudescent cryptococcosis, caused by Cryptococcus gattii (molecular type VGII),
      over a 13-year period in a Birman cat.
AB  - A 17-year-old desexed male Birman cat presented with a fleshy mass protruding
      from the left ear canal. A culture from the mass revealed a heavy growth of
      Cryptococcus gattii (molecular type VGII, serotype B). The lesion resolved with
      antifungal therapy over 8 weeks. Itraconazole was continued indefinitely due to
      persistent high serum cryptococcal antigen titres. The cat was euthanased 12
      months later due to the acute development of hindlimb ataxia and collapse which
      may or may not have been attributable to cryptococcosis. This cat had first
      presented when 4 years of age with a 3-week history of inappetance, sneezing and
      serous nasal discharge. Culture of swabs from both nostrils were positive for C.
      gattii (VGII). Fluconazole therapy produced steady improvement over a 6 month
      period, at which time therapy was discontinued. The cat presented 9 months later
      for sneezing, again with a positive culture of C. gattii from the nasal cavity.
      Antifungal therapy was continued for 8 months, after which time cultures were
      negative and symptoms resolved. Three episodes of cryptococcosis in a cat over a
      13-year period were thus documented. Importantly, the two C. gattii isolates,
      obtained 13 years apart, were identical using DNA fingerprinting and random
      amplification of polymorphic DNA (RAPD) analysis.

PMID- 16966176
TI  - Cutaneous mucormycosis in a young, immunocompetent girl.
AB  - We report a case of cutaneous mucormycosis in a healthy, immunocompetent young
      girl (age 14 years). The patient had a 5-year history of a slowly enlarging,
      erythematous plaque with slight elevated, scaling, circinate borders on the right
      thigh. Histopathology showed a granulomatous infiltrate with broad, pale, non
      septate hyphae. Mycological study identified Mucor hiemalis (Wehmer).

PMID- 16966177
TI  - Phialemonium curvatum arthritis of the knee following intra-articular injection
      of a corticosteroid.
AB  - Phialemonium curvatum arthritis of the knee developed in a diabetic man following
      intra-articular injection of a corticosteroid. Cure was achieved with a 6-week
      course of intravenous amphotericin B deoxycholate. P.curvatum is commonly found
      in the environment and is often considered a contaminant; yet, its pathogenic
      potential should be seriously considered in selected patients.

PMID- 16966178
TI  - Fluconazole resistance mechanisms in Candida krusei: the contribution of efflux
      pumps.
AB  - The main resistance mechanism for fluconazole in Candida krusei is the diminished
      sensitivity of the target enzyme cytochrome P450 sterol 14 alpha-demethylase
      (CYP51) to inhibition by azole agents. An alternative mechanism of resistance,
      efflux-pump activity, has been proposed. The aim of our study was to find out the
      possible contribution of efflux-pumps in conferring resistance to fluconazole in
      33 C. krusei isolates from different clinical sources. The activity of efflux
      pumps was checked using the inhibitor CCCP (carbonyl cyanide 3-chloro
      phenylhydrazone), which decreases the minimum inhibitory concentration (MIC) when
      resistance is attributed. We established a concentration of 0.5 microg/ml of
      CCCP. The susceptibility patterns of our isolates for five antifungal drugs
      (amphotericin B, fluconazole, itraconazole, flucytosine and voriconazole) were
      determined according to an NCCLS M27-A2 protocol modification (Sensititre Yeast
      One). We tested all the strains before and after adding CCCP to the RPMI medium.
      The MIC90s and ranges of the drugs were identical before and after addition of
      CCCP. The MIC for fluconazole was higher than for the other antifungals. The new
      triazoles were active and the MICs were lower, although this should be
      interpreted carefully as the drugs showed different cut-offs. Only one isolate
      showed a two-fold decrease in MIC to fluconazole when CCCP was added. We did not
      find any multi-resistant strains. According to our study with C. krusei, CCCP
      inhibited efflux-pumps do not play a significant role in resistance to
      fluconazole.

PMID- 16966179
TI  - Real-time PCR TaqMan assay for detecting Trichophyton tonsurans, a causative
      agent of tinea capitis, from hairbrushes.
AB  - Tinea capitis caused by Trichophyton tonsurans is currently an epidemic in the
      United States, Europe, and Japan, and the cultivation of this microorganism is
      necessary for a definitive diagnosis. We recently developed a real-time PCR
      TaqMan assay as a culture-independent method for the rapid detection of T.
      tonsurans from hairbrushes.

PMID- 16966180
TI  - Evaluation and optimization of radioprotective activity of Coronopus didymus
      Linn. in gamma-irradiated mice.
AB  - PURPOSE: To evaluate and optimize the radioprotective ability of the most potent
      fraction of an aqueous extract of Coronopus didymus in whole body gamma
      irradiated Swiss albino mice and to evaluate the antioxidant status and lipid
      peroxidation of the livers of the surviving mice. To correlate the free radical
      scavenging studies with in vivo radioprotection ability. MATERIALS AND METHODS:
      Swiss albino mice were treated with either vehicle or the different doses of
      extract/fraction suspension by an i.p. route, 30 min before exposure to 10 Gy
      gamma-irradiation and the animals were monitored twice daily for any signs of
      radiation toxicity and mortality. Radiation dose response (7-11 Gy), optimization
      of route, time of drug administration and evaluation of dose response factor
      (DRF) at the best dose of the fraction was studied. Endogenous antioxidant status
      and lipid peroxidation of the livers of the mice surviving on the 31st day was
      evaluated by using spectrophotometric methods. RESULTS: The most active free
      radical scavenging fraction (CDF1) as assessed by competition kinetic studies
      using pulse radiolysis showed maximum in vivo radioprotection of 70% at a dose of
      400 mg/kg body weight (bw) compared to corresponding 10 Gy irradiated control.
      Optimum radioprotection was observed upon i.p. administration, 30 min prior to 10
      Gy irradiation and DRF at a dose of 400 mg/kg bw for 30 day survival was found to
      be 1.07. The levels of endogenous antioxidant enzymes and lipid peroxidation in
      the CDF1 treated surviving mice were found to reverse back to their normal
      levels. CONCLUSIONS: The optimum dose, time and route of drug administration for
      maximum radioprotection by CDF1 were determined. The reversal of the levels of
      endogenous antioxidant enzymes and lipid peroxidation indicates reduced oxidative
      stress in CDF1 treated surviving mice.

PMID- 16966181
TI  - Radiation-induced bystander effects and adaptive response in murine lymphocytes.
AB  - PURPOSE: To study the bystander effects of gamma-radiation in murine lymphocytes
      using irradiated conditioned medium (ICM) generated from irradiated lymphocytes.
      METHODS: Proliferation response of unirradiated lymphocytes to mitogen
      concanavalin A (con A) in presence of ICM, collected from gamma-irradiated
      lymphocytes (60Co source; 0.35 Gy/min; 0.1-1 Gy), was studied by 3H-thymidine
      incorporation and also by dye dilution using carboxyfluorescein succinimidyl
      ester (CFSE). Expression of proliferation markers, interleukin 2 receptor alpha
      chain (CD25) and cyclin D in ICM treated lymphocytes was analyzed by labeling
      with specific antibodies. Intracellular reactive oxygen species (ROS) and
      apoptosis were estimated by flow cytometry using dichlorodihydrofluorescein
      diacetate (H2DCFDA) and propidium iodide, respectively. Nitric oxide (NO) was
      measured using Griess reagent. RESULTS: Proliferation response to con A in
      unirradiated lymphocytes was enhanced in the presence of ICM with maximum
      enhancement observed in the presence of 0.5 Gy ICM. Augmentation of proliferation
      in the presence of ICM was accompanied by an increase in CD25 and cyclin D
      expression, enhanced ROS and NO generation. ICM pretreated lymphocytes showed
      adaptive response to radiation which was not abrogated by wortmannin, a
      phosphatidyl inositol 3-kinase (PI3K) inhibitor. CONCLUSION: Soluble factors
      released from irradiated lymphocytes initiate a signaling cascade in unirradiated
      lymphocytes resulting in increased response to mitogen and radioresistance which
      may have an important role in radiation-induced immunomodulation.

PMID- 16966182
TI  - The magnitude and time-dependence of the apoptotic response of normal and
      malignant cells subjected to ionizing radiation versus hyperthermia.
AB  - PURPOSE: The purpose of the study was to examine the optimal time of exposure and
      dose of heat and ionizing radiation that results in the killing of human cancer
      cells in vitro via apoptosis vs. necrosis. MATERIALS AND METHODS: Human mammary
      carcinoma, colorectal carcinoma and normal bovine capillary endothelial (BCE)
      cell lines were subjected to 20 Gy ionizing radiation and 6, 12, 24, and 72 h
      later assessed for apoptosis using detection of apoptotic bodies and caspase
      assays. Necrosis was detected by loss of cells from the surface and lactate
      dehydrogenase (LDH) release. The colorectal carcinoma cells were subjected to
      hyperthermia using temperatures ranging from 39 - 44 degrees C for 5, 15 or 45
      min. exposures and at varying times post-treatment, apoptosis and necrosis were
      measured. RESULTS: In response to ionizing radiation, none of the cells underwent
      necrosis and some cell types apoptosed 24 and 72 h posttreatment. The colorectal
      cancer cells exhibited a steady increase of apoptosis at 6, 12, and 24 h. When
      these cells were exposed to 40 degrees C for 5 min, caspases increased within 6 h
      and a significant fraction (50%) of cells apoptosed. If the time of exposure to
      40 degrees C was increased to 15 or 45 min, 80% and 100% of the dying cells
      apoptosed, respectively. A temperature of 39 degrees C did not cause cell death
      even after 45 min exposures. If heat was elevated to 42 or 44 degrees C,
      increased necrosis was observed with a corresponding decrease in apoptosis.
      CONCLUSIONS: These studies reveal time and temperature dependent in vitro cell
      responses to ionizing radiation and water-bath hyperthermia.

PMID- 16966183
TI  - Clastogenicity and aneuploidy in newborn and adult mice exposed to 50 Hz magnetic
      fields.
AB  - PURPOSE: To detect possible clastogenic and aneugenic properties of a 50 Hz, 650
      muT magnetic field. MATERIALS AND METHODS: The micronucleus test with CREST
      (Calcinosis, Raynaud's phenomenon, Esophageal dismotility, Sclerodactility,
      Telangectasia) antibody staining was performed on liver and peripheral blood
      sampled from newborn mice exposed to an ELF (Extremely Low Frequency) magnetic
      field during the whole intra-uterine life (21 days), and on bone marrow and
      peripheral blood sampled from adult mice exposed to the same magnetic field for
      the same period. RESULTS: Data obtained in newborn mice show a significant
      increase in micronuclei frequencies. In absolute terms, most of the induced
      micronuclei were CREST-negative (i.e., formed by a chromosome fragment). However,
      in relative terms, ELF exposure caused a two-fold increase in CREST-negative
      micronuclei and a four-fold increase in CREST-positive micronuclei (i.e., formed
      by a whole chromosome). No significant effect was recorded on exposed adults.
      CONCLUSIONS: These findings suggest the need for investigation of aneugenic
      properties of ELF magnetic fields in order to establish a possible relationship
      to carcinogenesis.

PMID- 16966184
TI  - Induction of radiation resistance by a heat shock protein inhibitor, KNK437, in
      human glioblastoma cells.
AB  - PURPOSE: We examined the effects of a heat shock protein (hsp) inhibitor, N
      formyl-3, 4-methylenedioxy-gamma-butyrolactam (KNK437), on the radiosensitivity
      of human glioblastoma cells (A-172). MATERIALS AND METHODS: Effects of KNK437 on
      radiosensitivity and cell cycle regulation were examined using colony formation
      assays, flow cytometry analysis and Western blot analysis. KNK437 was added to
      the culture medium 1 h before X-ray irradiation at 50, 100 or 300 microM final
      concentration. RESULTS: KNK437 induced the resistance of A-172 cells and human
      squamous cell carcinoma cells (SAS) to X-rays. Flow cytometry analysis showed
      that KNK437 alone efficiently induced A-172 cells to enter G2/M phase. Though A
      172 cells irradiated with X-rays at 6 Gy showed no clear change in the cell
      cycle, the irradiated cells were induced to enter G2/M phase when they had been
      pre-treated with KNK437. By Western blot analysis, p53, 14-3-3sigma and cell
      division cycle 2 (cdc2) proteins that function in G2 arrest were observed to be
      persistently accumulated or phosphorylated in KNK437-treated cells, regardless of
      X-ray irradiation. CONCLUSIONS: These results show that KNK437 causes cells to be
      resistant to radiation, and that this might be correlated with maintenance of G2
      arrest in the cell cycle regulation.

PMID- 16966185
TI  - Risk of radiation-induced subcutaneous fibrosis in relation to single nucleotide
      polymorphisms in TGFB1, SOD2, XRCC1, XRCC3, APEX and ATM--a study based on DNA
      from formalin fixed paraffin embedded tissue samples.
AB  - PURPOSE: In two previously published studies, associations with risk of radiation
      induced subcutaneous fibrosis were found for single nucleotide polymorphisms
      (SNP) in TGFB1 (transforming growth factor beta 1 gene), XRCC1 (X-ray repair
      cross-complementing 1 gene), XRCC3 (X-ray repair cross-complementing 3 gene),
      SOD2 (manganese superoxide dismutase gene) and ATM (gene of ataxia telangiectasia
      mutated). The present study was conducted to seek a confirmation of these
      findings. MATERIALS AND METHODS: Like the 41 patients previously investigated,
      the 120 subjects included in the present study were accrued from a historical
      cohort of 319 post-mastectomy radiotherapy patients. All patients received hypo
      fractionated radiotherapy. The TGFB1 position--509, codons 10 and 25, XRCC1
      codons 194, 280 and 399, XRCC3 codon 241, SOD2 codon 16, ATM codon 1853 and APEX
      (apurinic/apyrimidinic exonuclease gene) codon 148 polymorphisms were assessed
      based on archival histological material. Differences in fibrosis risk were
      quantified from dose-response assessments. RESULTS: For none of the investigated
      polymorphisms, significant associations with risk of subcutaneous fibrosis were
      observed. A detailed analysis did not reveal any obvious explanation for the
      discrepancy between the previous and the present study. CONCLUSION: The
      previously observed associations with risk of radiation-induced subcutaneous
      fibrosis could not be replicated in the present study. Further studies are needed
      to elucidate the influence of genetic variation upon normal tissue
      radiosensitivity.

PMID- 16966186
TI  - Biological effects of anhydrobiosis in an African chironomid, Polypedilum
      vanderplanki on radiation tolerance.
AB  - PURPOSE: Anhydrobiotic organisms are known to have an extremely high tolerance
      against a range of stresses. However, the functional role of anhydrobiosis in
      radiation tolerance is poorly understood, especially in development following
      irradiation. The present study aims to evaluate effects of anhydrobiosis on
      radiation tolerance in an anhydrobiotic insect, Polypedilum vanderplanki.
      MATERIALS AND METHODS: Larval survival (48 h), anhydrobiotic ability,
      metamorphosis and reproduction after exposure to 1-9000 Gy of gamma-rays at the
      larval stage were compared between anhydrobiotic (dry) and normal (wet) phases.
      RESULTS: Wet larvae were killed in a dose-dependent manner at doses higher than
      2000 Gy, and all died within 8 h after 4000 Gy exposure. In contrast, dry larvae
      survived even 5000 Gy, and some of them still tolerated 7000 Gy and were alive at
      48 h after rehydration. Moreover, greater radiotolerance of dry larva, compared
      to wet ones, was demonstrated in terms of metamorphoses. However, anhydrobiosis
      did not protect against radiation damage in terms of producing viable offspring.
      CONCLUSION: These results indicate that anhydrobiosis enhances radiotolerance,
      resulting in increases of successful metamorphoses.

PMID- 16966187
TI  - Constitutive mRNA expression of DNA repair-related genes as a biomarker for
      clinical radio-resistance: A pilot study in prostate cancer patients receiving
      radiotherapy.
AB  - PURPOSE: Repair of radiation-induced DNA damage is believed to play a critical
      role in the development of adverse reactions in radiotherapy patients.
      Constitutive mRNA expression of repair genes was investigated in such patients to
      analyze whether expression patterns are predictive for therapy-related acute side
      effects. MATERIALS AND METHODS: Prostate cancer patients (n = 406) receiving
      intensity-modulated radiotherapy were recruited in a prospective epidemiological
      study. Adverse effects were monitored during therapy using common toxicity
      criteria. For expression analyses, samples from 58 patients were selected
      according to their observed grade of clinical side effects to radiotherapy.
      Expression profiles were generated from peripheral blood lymphocytes using
      customized cDNA-arrays which carried probes for 143 DNA repair or repair-related
      genes. In addition, expression of selected genes was confirmed by quantitative
      real-time reverse transcription PCR (RT-PCR). Constitutive mRNA expression
      profiles were analyzed for predicting acute clinical radiosensitivity or radio
      resistance. RESULTS: Cluster analysis identified 19 differentially expressed
      genes. Many of these genes are involved in DNA double strand break repair.
      Expression levels of these genes differed up to 7-fold from the mean of all
      patients whereas expression levels of housekeeping genes varied only up to 2
      fold. High expression of the identified genes was associated with a lack of
      clinical radiation sensitivity thus indicating radio-resistance. CONCLUSIONS:
      Constitutive expression of DNA repair-related genes may affect the development of
      acute side effects in radiotherapy patients, and high expression levels of these
      genes seem to support protection from adverse reactions.

PMID- 16966188
TI  - Serotonin transporter genotype and acute subjective response to amphetamine.
AB  - The authors have previously shown an effect of dopamine transporter genotype on
      acute subjective responses to d-amphetamine, which may affect risk of addiction.
      They now report the results of an evaluation of the role of the serotonin
      transporter gene (HTT) using a double-blind, placebo-controlled, crossover design
      in which subjects (N = 101) completed self-report measures of subjective effect.
      The separate and combined analyses of the gene-linked polymorphic region (5
      HTTLPR) and the Intron 2 VNTR suggest that these two HTT polymorphisms may
      contribute to acute subjective responses to d-amphetamine with a small effect.

PMID- 16966189
TI  - Integrating tobacco cessation treatment into mental health care for patients with
      posttraumatic stress disorder.
AB  - The integration of tobacco cessation treatment into mental health care for
      posttraumatic stress disorder (PTSD), known as Integrated Care (IC), was
      evaluated in an uncontrolled feasibility and effectiveness study. Veterans (N =
      107) in PTSD treatment at two outpatient clinics received IC delivered by mental
      health practitioners. Outcomes were seven-day point prevalence abstinence
      measured at two, four, six, and nine months post-enrollment and repeated seven
      day point prevalence abstinence (RPPA) obtained across three consecutive
      assessment intervals (four, six, and nine months). Abstinence rates at the four
      assessment intervals were 28%, 23%, 25%, and 18%, respectively, and RPPA was 15%.
      The number of IC sessions and a previous quit history greater than six months
      predicted RPPA. Stopping smoking was not associated with worsening PTSD or
      depression.

PMID- 16966190
TI  - Comorbid schizophrenia and substance abuse: a review of epidemiology and course.
AB  - Over the last dozen years, our knowledge regarding comorbid schizophrenia (SCZ)
      and substance use disorder (SUD) has evolved in several ways. First, the rate of
      lifetime comorbid SCZ-SUD appears to have increased another 20-30%, so now about
      70-80% of persons with SCZ have lifetime SUD. Second, early remission of SUD has
      become commonplace among patients with SCZ, perhaps outnumbering the number of
      SCZ-only patients as well as those with active SCZ-SUD. Third, sustained SUD
      remission is well demonstrated, though the rates may yet be low. Fourth, research
      on comorbid SCZ-SUD is filling out our knowledge in many areas, including the
      characteristics of SCZ patients at risk for SUD, reasons SCZ patients seek out
      substances, effects of various substances on SCZ course and symptoms, and
      obstacles to SUD recovery in people with SCZ. The influence of SUD treatment and
      self-help on epidemiology and course has not been adequately evaluated. Primary
      prevention and early treatment of SUD in SCZ patients are still relatively
      neglected, though they offer our greatest hope for enhancing the lives of people
      with SCZ and improving the cost efficacy of care.

PMID- 16966191
TI  - Exploration of the relationship between drinking intensity and quality of life.
AB  - This work explored the association between quality of life and drinking intensity
      in the Project MATCH sample. Tobit regression models were evaluated to assess the
      relationship between quality of life indicators (eg, measures of depression,
      adverse consequences, and others) and drinks per drinking day (DDD), and to
      assess modification or confounding of DDD by subject characteristics and
      treatment type. Each quality of life indicator improved with decreased DDD.
      Gender and ethnicity modified the DDD effect for some outcomes, with DDD exerting
      a greater influence on quality of life in women and non-Hispanic whites.

PMID- 16966192
TI  - Using addiction severity profiles to differentiate cocaine-dependent patients
      with and without comorbid major depression.
AB  - This study compared pretreatment addiction severity profiles of 339 abusers in
      three diagnostic groups: cocaine dependence only (CO), cocaine dependence with
      substance-induced major depression (SIMD), and cocaine dependence with
      independent major depression (IMD). Depressed subjects reported more severe
      problems than non-depressed subjects across numerous domains, regardless of
      diagnostic etiology. These findings support the need for specialized treatment
      approaches targeting depressive symptoms or life stress for cocaine-dependent
      patients with IMD or SIMD, though patients with IMD may require additional
      attention for chronic and comorbid psychiatric and medical problems.

PMID- 16966193
TI  - Substance abuse treatment and criminal justice involvement for SSI recipients:
      results from Washington state.
AB  - This study examined the association between receiving substance abuse treatment
      and subsequent criminal justice involvement. The sample consisted of Supplemental
      Security Income (SSI) recipients in the state of Washington that were determined
      to be in need of treatment. Fifty-two percent of those clients entered substance
      abuse treatment during the study period, while 48% did not. Arrests, felony
      convictions and convictions for less serious crimes were tracked for 8343 adults
      for one year following the end of an index treatment episode. Results showed that
      entering treatment was associated with reduced risks for each outcome. In
      addition, further analyses were conducted just on those entering treatment. Among
      that subset of the study population, the completion of treatment and having an
      episode of treatment lasting at least 90 days were both associated with reduced
      criminal justice risks. These results suggest that efforts to provide substance
      abuse treatment for SSI recipients have the potential to provide substantial
      public benefits.

PMID- 16966194
TI  - A gendered analysis of Canadian Aboriginal individuals admitted to inpatient
      substance abuse detoxification: a three-year medical chart review.
AB  - This study examined gender differences within a sample of Canadian Aboriginal
      individuals admitted to an inpatient, hospital-based substance abuse
      detoxification program. Even though alcohol was the most frequent primary drug of
      detoxification for both genders, women received proportionately higher rates of
      cocaine or opiate detoxification diagnoses. In addition to a younger age, females
      reported higher rates of physical and sexual abuse. Women were also administered
      antidepressants, antibiotic medication protocols, and more medical evaluation
      tests. It appears that Canadian Aboriginal women have a diverse set of
      psychological and medical needs. This study demonstrates the need for
      detoxification programs to address the substantial rates of intravenous drug use
      and the associated risk of infectious disease (eg, Hepatitis C, HIV) among this
      treatment-seeking population.

PMID- 16966195
TI  - The relationship between perceived exposure to promotional smoking messages and
      smoking status among high school students.
AB  - Data on self-reported perceived exposure to pro-smoking messages were collected
      from 1,608 high school students surveyed through the ASPIRE (A Smoking Prevention
      Interactive Experience) Program in Houston, Texas, in 2003. Results indicated
      that high school smoking quitters had approximately twice the odds of perceived
      exposure to pro-smoking messages as nonsmokers through billboard advertisements
      (Adjusted Odds Ratio [AOR] = 2.04, 95% CI: 1.09, 3.81), newspapers & magazines
      (AOR: 1.97, 95% CI: 1.09, 3.56), and movies (AOR: 1.94, 95% CI: 1.03, 3.65).
      Smoking experimenters marginally perceived more exposure to pro-smoking radio
      messages (AOR = 1.31, 95% CI: 1.04, 1.67) and billboard advertisements (AOR =
      1.28, 95% CI: 1.02, 1.61) compared to nonsmokers. Lastly, current smokers were
      1.82 times as likely to report exposure to pro-smoking poster advertisements as
      nonsmokers (95% CI: 1.19, 2.79, p < or = .05). These findings suggest that
      experimenters and quitters may pay more attention to smoking advertisements than
      nonsmokers and current smokers.

PMID- 16966196
TI  - Self-harm and suicidal behavior in women with comorbid PTSD and substance
      dependence.
AB  - This study examined the frequency, methods, and correlates of self-harm and
      suicidal behavior in 65 outpatient women with comorbid posttraumatic stress
      disorder (PTSD) and substance dependence (SD). Results showed high rates of
      suicide attempts, self-harm, suicidal ideation, and self-harm ideation for the
      prior three months. The most common methods were overdosing and
      cutting/scratching. Both PTSD and SD were perceived as contributing to self-harm
      and suicidal behavior. Women who had and had not engaged in such behavior
      differed in SD diagnoses and reasons for staying safe, but not in the number or
      type of traumatic experiences, age at first trauma, or substance abuse diagnoses.

PMID- 16966197
TI  - Readiness to quit cigarette smoking, intimate partner violence, and substance
      abuse among arrested violent women.
AB  - Cigarette smoking is a leading cause of preventable mortality in the United
      States. Not much data are available regarding the prevalence and correlates of
      cigarette smoking in female perpetrators of intimate partner violence (IPV).
      Ninety-eight arrested violent women were recruited from court-referred batterer
      intervention programs. The prevalence of smoking in the sample was 62%. Smokers
      reported higher levels of substance abuse, psychopathology, general violence, and
      IPV perpetration and victimization than nonsmokers. Most smokers (65%) indicated
      a desire to quit within the next year. The results highlight the importance of
      screening for cigarette smoking in violence intervention programs and offering
      assistance to those who choose to quit.

PMID- 16966198
TI  - Response to "transferring methadone-stabilized pregnant patients to
      buprenorphine".

PMID- 16966200
TI  - Mismatch in the transtheoretical model?

PMID- 16966201
TI  - Buspirone for treatment of marijuana dependence: a pilot study.

PMID- 16966202
TI  - Zolpidem and dextromoramide abuse with increased metabolism.

PMID- 16966204
TI  - Loyalty.

PMID- 16966205
TI  - John B. Murphy: unique among American surgeons.
AB  - John B. Murphy (1857-1916), one of the most outstanding and controversial
      surgeons of his age, was a product of the strong clinical programs that developed
      in Chicago in the late 19th century. Heavily influenced by Christian Fenger,
      surgeon and surgical pathologist, he went to Europe for training under Theodore
      Billroth and others. He applied results of his dog lab experiments to human
      problems while maintaining a large private practice. He is best known for his
      teaching clinics, for his groundbreaking work with a button for intestinal
      anastomosis, and for encouraging early operation in appendicitis. Though often in
      trouble with his fellow surgeons who accused him of stealing patients, especially
      in the Haymarket affair and when Theodore Roosevelt was shot, he nevertheless
      made many contributions to the care of surgical patients and development of
      academic surgery.

PMID- 16966206
TI  - Prostaglandin E1 maintains structural integrity of intestinal mucosa and prevents
      bacterial translocation during experimental obstructive jaundice.
AB  - The absence of bile in the gut lumen induces mucosal injury and promotes
      bacterial translocation (BT). Prostaglandin E (PGE) has a protective effect on
      the mucosal layer of the alimentary tract. We hypothesize that PGE1 may prevent
      BT by its beneficial action on the mucosa of the small bowel. Thirty Wistar
      albino rats were divided equally into 3 groups; Group 1 (control) underwent sham
      laparotomy, group 2 obstructive jaundice (OJ) and group 3 (OJ + PGE1) underwent
      common bile duct (CBD) ligation and transection. Groups 1 and 2 received; 1 mL
      normal saline and group 3 received 40 mg of the PGE1 analogue misoprostol
      dissolved in 1 mL normal saline administered by orogastric tube once daily. After
      7 days, laparotomy and collection of samples for laboratory analyses were
      performed, including bacteriological analysis of intestine, mesenteric lymph
      nodes (MLNs), and blood, and histopathologic examination of intestinal mucosa to
      determine mucosal thickness and structural damage. Serum bilirubin and alkaline
      phosphatase levels confirmed OJ in all animals with CBD transection. The mucosal
      damage score was significantly reduced in jaundiced animals receiving PGE1
      compared to jaundiced controls (2.15 +/- 0.74 vs 5.3 +/- 0.59; p < .00001) and
      mucosal thickness was greater (607 +/- 59.1 microm vs. 393 +/- 40.3 microm; p <
      .00001). The incidence of BT to MLNs decreased from 90% to 30% (p < .02) when
      jaundiced rats received PGE1. PGE1 treatment reduced the detection rate of viable
      enteric bacteria in the blood from 60% to 10% (p < .057). We conclude that
      administration of PGE1 provides protection against OJ-induced atrophy and damage
      of intestinal mucosa, and thereby prevents translocation of enteric bacteria to
      underlying tissues.

PMID- 16966207
TI  - Role of peritoneal lavage in adhesion formation and survival rate in rats: an
      experimental study.
AB  - Following laparotomy, almost 95% of patients develop adhesions. To prevent
      adhesion formation, peritoneal lavage has been investigated and many different
      lavage solutions have been proposed. In this study, different peritoneal lavage
      solutions were evaluated, testing their ability to prevent adhesion formation.
      Three consecutive steps were followed: (1) The lethal dose of Eschericia coli
      injected in the rat peritoneal cavity was determined, (2) the morbidity and
      mortality rates of different solutions for peritoneal lavage (i.e., saline, twice
      distilled water, antiseptics, and antibiotics solutions) was investigated, and
      (3) the capability of the different lavage solutions to prevent adhesion
      formation was tested. Two hundred and ninety-eight rats were employed in this
      study. After intraperitoneal injection of E. coli, infection (clinical signs and
      animal vitality), adhesion formation (explorative laparoscopy, peritoneumgraphy
      and Zuhlke scale grading), and animal performance status were investigated. All
      differences were evaluated by chi-square and analysis of variance (ANOVA) tests.
      Saline solution showed a low morbidity rate with no deaths. Twice-distilled water
      was associated with 100% mortality rate, as opposed to 45-75% for antiseptics,
      and 0-3% mortality for antibiotics. Antibiotics determined higher adhesion
      formation by Zuhlke score as compared to saline solution (p < .001), while no
      difference was observed between antiseptics and saline (p = NS). Peritoneal
      lavage with 37 degrees C saline solution was associated with low adhesion
      formation and high survival rate as compared to twice-distilled water and
      antiseptics. Antibiotics solutions had high survival rate and high adhesion
      formation. Twice-distilled water and antisepsis should be avoided when based on
      the data obtained in this work.

PMID- 16966208
TI  - Hemoglobin-based oxygen carrier does not improve survival of ischemic rat island
      groin flaps.
AB  - Reducing reperfusion injury to skin flaps is an effective means to improve the
      survival of the flap. By enhancing oxygen delivery to the microcirculation within
      the flap, ischemia-reperfusion injury should be decreased, improving the flap's
      survival. This study evaluated the effects of a hemoglobin-based oxygen carrier
      (Oxyglobin) on the development of necrosis and survival of ischemic rat island
      groin flaps. Sprague-Dawley rats were randomly assigned to one of three treatment
      groups. A groin flap was elevated on each rat and subjected to 9 h of ischemia.
      Rats in group I were given an intravenous infusion of 0.9% saline prior to
      elevation of the skin flap. Rats in group II were given an intravenous infusion
      of Oxyglobin prior to elevation of the skin flap. Rats in group III were given a
      low-dose intravenous infusion of Oxyglobin following the 9 h of ischemia, just
      prior to reperfusion. The flaps were monitored for 7 days postoperatively for
      necrosis. The percentage of flap necrosis was recorded at the end of 7 days. All
      rats were euthanized at the completion of the study and the flaps were harvested
      for histopathological analysis. No significant difference was noted in the
      survival of the flaps or the degree of necrosis in the rats treated with
      Oxyglobin compared to the control group. Thus, pre-reperfusion treatment with
      Oxyglobin did not improve the percentage of flap survival, or the degree of
      severity of necrosis in rat groin flaps subjected to 9 h of ischemia.

PMID- 16966209
TI  - The "opening time" and "pelvic floor electromyographic lag time": two novel tools
      in the assessment of the anorectal evacuation time.
AB  - Rectal evacuation necessitates rectal contraction and pelvic floor muscles
      relaxation; it is not known which action precedes the other. We investigated the
      hypothesis that pelvic floor muscles relaxation precedes rectal contraction so
      that rectal contents find the anal canal already opened. Electromyographic
      activity of the external anal sphincter as well as anal and rectal pressures were
      recorded during rectal balloon distension and evacuation. Pelvic floor muscles
      electromyographic lag time (time from start of pelvic floor muscles relaxation to
      start of evacuation) and opening time (time from start of rectal contraction to
      start of evacuation) were measured. Rectal balloon distension in increments of 20
      mL up to 100 mL effected progressive increase of both external anal sphincter
      electromyography and anal pressure. At 120 mL balloon distension up to 180 mL,
      external anal sphincter electromyography and anal pressure exhibited gradual
      decrease whereas rectal pressure showed no changes. At 200 to 220 mL rectal
      balloon distension, rectal pressure increased and anal pressure decreased, while
      external anal sphincter showed no electromyographic activity; rectal balloon was
      expelled. The opening time recorded a mean of 1.8 +/- 0.7 s and pelvic floor
      muscles electromyographic lag time of 2.2 +/- 0.9; the two recordings showed no
      significant difference (p > .05). These, two diagnostic tools in anorectal
      investigations are presented: the opening time and pelvic floor muscles
      electromyographic lag time. Pelvic floor muscles relaxation preceded rectal
      contraction. As there is no significant difference between opening time and
      pelvic floor muscles electromyographic lag time, it appears easier to apply the
      latter as it is simple, objective, and noninvasive.

PMID- 16966210
TI  - Selectin inhibition modulates NF-kappa B and AP-1 signaling after liver
      ischemia/reperfusion.
AB  - The infiltration of neutrophils after ischemia and reperfusion (I/R) is
      facilitated by the expression of adhesion molecules on the surface of both
      leukocytes and endothelial cells. Adhesion molecules of the selectin family are
      of particular importance at the onset of neutrophil mediated injury, as
      demonstrated by the occurrence of many cellular interactions with the final
      extravasation of inflammatory leukocytes at the site of I/R damage. Previous
      studies demonstrated a prevention of neutrophil extravasation and protection of
      ischemic damage when a small anti-selectin molecule was used. In this study, we
      tested a new small anti-selectin compound (OC-229) in a murine model of partial
      hepatic I/R. The aim of this study was to determine the effect of OC-229 on liver
      function and histology after I/R and to evaluate its role in the modulation of
      the inflammatory molecular signaling pathways of NF-kappa B and AP-1 under the
      same experimental condition. Mice subjected to 90 min of partial (70-80%) hepatic
      ischemia and 3 h of reperfusion were divided into three groups (n = 9/group):
      sham, ischemic control, and treated group, which received 25 mg/kg of the anti
      selectin small molecule OC-229. These groups were studied when the treatment was
      given at the time of reperfusion (no pretreatment was given). The parameters
      measured at 3 h of reperfusion included liver function tests (ALT and AST), liver
      histology, and liver tissue electrophoretic mobility shift assay (EMSA) for NF
      kappa B and AP-1. It was demonstrated that the multiselectin inhibitor OC-229
      offered significant protection for the ischemic liver when given at 25 mg/kg at
      the time of reperfusion. ALT and AST serum levels significantly decreased when
      the ischemic control and the group receiving OC-229 were compared (p = .01).
      Treated animals demonstrated better histological findings as well. The EMSA
      showed dissociation of NF-kappa B and AP-1 activity in the liver nuclear extracts
      after selectin inhibition treatment. A reduction in the activity of AP-1 and an
      increment in NF-kappa B activation was seen. In this work, we obtained evidence
      that the small-molecule selectin inhibitor OC-229 offered functional and
      histological protection of the ischemic liver when given at 25 mg/kg at the time
      for reperfusion. There was dissociation in the activation signals of NF-kappa B
      and AP-1. Increase in NF-kappa B and reduction of the activation of AP-1 were
      noted at 3 h of reperfusion.

PMID- 16966211
TI  - A low-cost and simple method to stop intraoperative leakage-type bleeding: use of
      the vancomycin-oxidized regenerated cellulose (ORC) sandwich.
AB  - Intraoperative bleeding may cause life-threatening complications in patients if
      such bleeding cannot be brought under control. Various materials are available
      for stopping such bleeding. However, there are some difficulties in the
      acquisition and application of these materials. The aim of this study was to
      investigate the efficiency of the low-cost and simple-to-prepare vancomycin
      oxidized regenerated cellulose (ORC) sandwich in surgical bleeding control.
      Thirty New Zealand rabbits were used for this purpose. The animals were separated
      into three groups as group 1 (n = 10), control group; group 2 (n = 10), oxidized
      regenerated cellulose (ORC) group; and group 3 (n = 10), vancomycin-ORC sandwich
      group. Left thoracotomies were performed on the rabbits under general anesthesia,
      and bleeding was created in the parietal pleura. The amount of bleeding in the
      groups was measured and compared. The amount of bleeding in the group in which
      the vancomycin-ORC sandwich was used was found to be less, compared to the other
      two groups. According to these results, we conclude that the vancomycin-ORC
      sandwich can be used safely in the control of intraoperative leakage-type
      bleeding, as the vancomycin-ORC sandwich is a low-cost, easily applied, and
      easily acquired material.

PMID- 16966215
TI  - Ligand up-regulation does not correlate with a role for CCR1 in pathogenesis in a
      mouse model of non-lymphocyte-mediated neurological disease.
AB  - CCR1 ligands, including CCL3, CCL5, and CCL7, are up-regulated in a number of
      neurological disorders in humans and animal models. CCR1 is expressed by multiple
      cell types in the central nervous system (CNS), suggesting that receptor
      signaling by neuronal cell types may influence pathogenesis. In the current
      study, the authors used a mouse model of retrovirus infection to study the
      contribution of CCR1 to neuropathogenesis in the absence of lymphocyte
      recruitment to the CNS. In this model, infection of neonatal mice with the
      neurovirulent retrovirus Fr98 results in increased expression of proinflammatory
      chemokines in the CNS, activation of glial cells, and development of severe
      neurological disease. Surprisingly, no difference in neuropathogenesis was
      observed between CCR1-sufficient and CCR1-deficient mice following infection with
      the neuropathogenic virus Fr98. CCR1 was also not necessary for control of virus
      replication in the brain or virus-induced activation of astroglia. Additionally,
      CCR1 deficiency did not affect the up-regulation of its ligands, CCL3, CCL5, or
      CCL7. Thus, CCR1 did not appear to have a notable role in Fr98-induced
      pathogenesis, despite the correlation between ligand expression and disease
      development. This suggests that in the absence of inflammation, CCR1 may have a
      very limited role in neuropathogenesis.

PMID- 16966216
TI  - Anti-CCL2 treatment inhibits Theiler's murine encephalomyelitis virus-induced
      demyelinating disease.
AB  - Theiler's murine encephalomyelitis virus induces a demyelinating disease (TMEV
      IDD) of the central nervous system (CNS) in susceptible mouse strains with
      accompanying histopathology characterized by mononuclear cell infiltrates. In
      susceptible strains of mice such as SJL, virus establishes a persistent infection
      in macrophages, induces a CNS infiltration by macrophages, T cells, and B cells,
      which results in chronic-progressive paralysis. In the present report the authors
      have investigated the functional role of CCL2 (monocyte chemotactic protein-1) in
      the induction and progression of demyelinating disease. Treatment of infected
      mice at day 0, 14, or 28 with anti-CCL2 resulted in a significant decrease in the
      clinical disease progression. Further analysis of anti-CCL2-treated mice revealed
      decreased CNS inflammation and mononuclear cell infiltration with an accompanying
      change in inflammatory cytokine responses. There was an overall decrease in the
      absolute numbers of CNS-infiltrating CD4+ T cells, macrophages, and B cells.
      Finally, anti-CCL2 treatment resulted in decreased viral load in the CNS. These
      data directly demonstrate a role for CCL2 in the pathogenesis of TMEV-IDD.

PMID- 16966217
TI  - Positron emission tomography imaging of peripheral benzodiazepine receptor
      binding in human immunodeficiency virus-infected subjects with and without
      cognitive impairment.
AB  - The pathology associated with late-stage dementia in human immunodeficiency virus
      (HIV) infection has been studied extensively. Neuropathological examination has
      demonstrated abundant activation and infection of macrophages/microglia termed
      HIV encephalitis. For obvious reasons, less is known regarding the neuropathology
      of minor cognitive impairment seen in earlier stages of HIV infection. The
      authors examined the utility of the peripheral benzodiazepine receptor ligand
      PK11195 in positron emission tomography (PET) imaging to assess
      microglial/macrophage activation in the brains of HIV-infected subjects with
      minor neurocognitive impairment in a cross-sectional study of 12 HIV infected
      individuals and 5 age-matched noninfected controls. Subjects were given a battery
      of neuropsychological tests in addition to assessing CD4 T-cell count and
      peripheral viremia followed by contrast enhanced magnetic resonance imaging (MRI)
      and PET with [15O]H2O followed by [11C](R)-PK11195. Two of the six
      neurocognitively impaired HIV-infected subjects demonstrated plasma viral
      breakthrough, whereas only one of six nonimpaired individuals demonstrated plasma
      viral load near the limits of detection. MRI demonstrated no abnormal enhancement
      and although atrophy was more prominent in impaired subjects, it was also present
      though to a lesser extent in nonimpaired subjects. None of the 12 HIV-infected
      subjects demonstrated increased retention of [11C](R)-PK11195 in the brain
      parenchyma compared to the 5 controls. These results suggest that either [11C](R)
      PK11195 PET assessment is insensitive to the degree of macrophage activation in
      HIV-associated minor neurocognitive impairment or macrophage activation is not
      the pathological substrate of this neurological condition.

PMID- 16966218
TI  - Brain CD8+ and cytotoxic T lymphocytes are associated with, and may be specific
      for, human immunodeficiency virus type 1 encephalitis in patients with acquired
      immunodeficiency syndrome.
AB  - CD8+ T cells infiltrate brains with human immunodeficiency virus type-1 (HIV-1)
      encephalitis (HIVE) and related animal models; their perineuronal localization
      suggests cytotoxic T cell (CTL)-mediated neuronal killing. Because CTLs have not
      been identified in acquired immunodeficiency syndrome (AIDS) brains, the authors
      identified their cytotoxic granules in autopsy AIDS brains with HIVE and without
      HIVE (HIVnE) plus controls (7 to 13 cases/group) and determined gene expression
      profiles of CTL-associated genes in a separate series of cases. CD3+ and CD8+ T
      cells were significantly increased (P < .01) in perivascular spaces and
      inflammatory nodules in HIVE but were rare or absent in brain parenchyma in HIVnE
      and control brains. Eight HIVE brains contained granzyme B+ T cells and five
      contained perforin+ T cells. Their T-cell origin was confirmed by colocalization
      of CD8 and granzyme B in the same cell and the absence of CD56+ natural killer
      cells. The CTLs directly contacted with neurons, as the authors showed previously
      for CD3+ and CD8+ T cells. CTLs were rare or absent in HIV nonencephalitis
      (HIVnE) and controls. Granzyme B and H precursor gene expression was up-regulated
      and interleukin (IL)-12A precursor, a maturation factor for natural killer cells
      and CTLs, was down-regulated in HIVE versus HIVnE brain. This study demonstrates,
      for the first time, CTLs in HIVE and shows that parenchymal T cells and CTLs are
      sensitive biomarkers for HIVE. Consequently, CD8+ T cells and CTLs could mediate
      brain injury in HIVE and may represent an important biomarker for productive
      brain infection by HIV-1.

PMID- 16966219
TI  - Efficacy of antiviral compounds in human herpesvirus-6-infected glial cells.
AB  - The beta-herpesvirus human herpesvirus-6 (HHV-6) is becoming increasingly
      recognized as an important pathogen in immunocompromised patients, particularly
      in post bone marrow transplant (BMT). Reactivation of latent HHV-6 resulting in
      encephalitis has been reported in BMT and stem cell transplant (SCT) patients.
      The development of HHV-6 encephalitis can be a fatal complication, the frequency
      of which is increasing likely due to improved diagnosis with quantitative
      polymerase chain reaction (PCR) of cerebrospinal fluid. There are currently no
      antiviral compounds approved for HHV-6, nor have any controlled clinical trials
      been conducted. The frequency and severity of HHV-6 encephalitis in both
      immunocompetent and immunocompromised patients necessitates studies on the
      usefulness of currently available anti-viral compounds. The authors compared the
      antiviral efficacy of four drugs currently used for cytomegalovirus (CMV)
      infection, a beta-herpesvirus sharing homology with HHV-6. In HHV-6A- and HHV-6B
      infected T cells, acyclovir, ganciclovir, foscarnet, and cidofovir exhibited
      antiviral activity consistent with that published in other studies. In HHV-6
      infected human astrocytes (U251), however, only foscarnet and cidofovir exhibited
      antiviral activity and this effect was restricted to infection with HHV-6 variant
      A. In pathological brain sections from patients with neurological disorders such
      as multiple sclerosis and epilepsy, HHV-6 has been localized to glial cells.
      Determination of antiviral activity in human glial fibrillary acidic protein
      (GFAP)-positive astrocytes of currently used antiviral compounds is essential for
      potential treatment of HHV-6 and neurological disorders. Our data highlight the
      necessity for further study of antiviral compound in HHV-6-infected glial cells
      as well as the development of more selective compounds for HHV-6.

PMID- 16966220
TI  - Cerebrospinal fluid is an efficient route for establishing brain infection with
      feline immunodeficiency virus and transfering infectious virus to the periphery.
AB  - Like human immunodeficiency virus (HIV), feline immunodeficiency virus (FIV)
      invades and infects the central nervous system (CNS) soon after peripheral
      infection. The appearance of viral RNA is particularly prominent in the
      cerebrospinal fluid (CSF), suggesting an efficient route of virus transfer across
      the blood-CSF barrier. This raises the concern whether this route can establish a
      stable viral reservoir and also be a source of virus capable of reseeding
      peripheral systems. To examine this possibility, 200 mul of cell-free NCSU1 FIV
      or FIV-infected choroid plexus macrophages (ChP-Mac) was directly injected into
      the right lateral ventricle of the brain. Negative controls were sham inoculated
      with uninfected ChP-Mac or virus-free culture supernatant and positive controls
      were infected systemically by intraperitoneal (i.p.) injection.
      Intracerebroventricular (i.c.v.) inoculation with cell-free FIV resulted in high
      levels of plasma FIV RNA detected as early as 1 to 2 weeks post inoculation in
      all cats. In each case, the plasma viremia preceded the detection of CSF viral
      RNA. Compared to i.p. cats, i.c.v. cats had 32-fold higher CSF viral loads, 8
      fold higher ratios of CSF to plasma viral load, and a 23-fold greater content of
      FIV proviral DNA in the brain. No FIV RNA was detected in plasma or CSF from the
      cats inoculated with FIV-infected ChP-Mac but an acute inflammatory response and
      a slight suppression of the CD4+:CD8+ ratio were observed. These results indicate
      that free FIV circulating in the CSF promotes infection of the CNS and provides a
      highly efficient pathway for the transfer of infectious virus to the periphery.

PMID- 16966221
TI  - Compartmentalization and evolution of feline immunodeficiency virus between the
      central nervous system and periphery following intracerebroventricular or
      systemic inoculation.
AB  - The emergence of distinct neuropathogenic strains resulting from the adaptation
      and the unique evolution of human immunodeficiency virus (HIV) in the brain may
      contribute to the development of HIV-induced neurological diseases. In this
      study, the authors tracked early changes in virus evolution and
      compartmentalization between peripheral tissues and the central nervous system
      (CNS) after intracerebroventricular (i.c.v.) or intraperitoneal (i.p.)
      inoculation of animals with cell-free feline immunodeficiency virus (FIV). Using
      the FIV-NCSU1 envelope V3-V4 heteroduplex tracking assay (HTA), the authors
      observed a rapid compartmentalization of envelope variants between the CNS and
      periphery. Animals receiving the i.c.v. inoculation showed two peaks of viral RNA
      in the cerebrospinal fluid (CSF) with very different HTA patterns. Compared to
      the initial viral peak in CSF, the second peak showed an increased
      compartmentalization from plasma, reduced viral diversity, and more divergence
      from the proviral DNA in peripheral blood mononuclear cells (PBMCs) and the
      choroid plexus. In contrast, changes in plasma over the same time period were
      small. Different animals harbored different FIV DNA genotypes with varied
      regional compartmentalization within the brain. These results demonstrated that
      the virus within the CNS experienced a relatively independent but variable
      evolution from the periphery. Initial penetration of virus into the CSF
      facilitated the development of brain-specific reservoirs and viral
      diversification within the CNS.

PMID- 16966222
TI  - Inflammatory response in human tick-borne encephalitis: analysis of postmortem
      brain tissue.
AB  - In Central European tick-borne encephalitis (TBE) mechanisms of tissue
      destruction are poorly understood. To evaluate the contribution of immunological
      mechanisms to tissue injury, the authors immunohistochemically analyzed paraffin
      embedded autoptic brain tissue of 26 human TBE cases. In the parenchymal
      compartment, there was a predominance of macrophages/microglia and cytotoxic T
      cells. In addition, it was found that granzyme B-expressing lymphocytes were in
      close contact with TBE-expressing neurons up-regulating caspase-3. These findings
      indicate that cellular and humoral pathways of the immune system, especially
      granzyme B-releasing cytotoxic T cells and macrophages/microglia, mainly
      contribute to tissue destruction in TBE.

PMID- 16966223
TI  - A placebo-controlled study of memantine for the treatment of human
      immunodeficiency virus-associated sensory neuropathy.
AB  - Distal sensory polyneuropathy (DSP) is the most frequent neurological
      complication of HIV infection. Neuropathic symptoms vary from mild paresthesias
      to severe pain that respond only partially to symptomatic treatment. Forty-five
      subjects with human immunodeficiency virus (HIV)-associated symptomatic DSP
      (SDSP) were enrolled in a randomized, multicenter, 16-week placebo-controlled
      study of memantine, an N-methyl-D-aspartate (NMDA) uncompetitive antagonist.
      Although memantine was well tolerated, no trend toward clinical benefit was
      observed. Results were similar to those of other pilot studies of memantine for
      neuropathic pain unrelated to HIV, suggesting that memantine is ineffective for
      the symptomatic treatment of HIV-associated SDSP.

PMID- 16966224
TI  - From the editor-the age of the techno-child?

PMID- 16966225
TI  - Abuse during pregnancy: current theory and new contextual understandings.
AB  - This study used Landenburger's theory, a process of leaving and recovering from
      an abusive relationship, as a framework to interview 35 pregnant women identified
      as being at high risk for abuse. Results are reported on 18 women who disclosed
      active abuse during the study. Landenburger's model was not a good fit. Our
      participants became trapped and endured violent relationships if they perceived
      this was the best situation for their unborn child. Additionally the chaos,
      instability, and lack of resources experienced by these women likely contributed
      to their inability to complete the four phases described by Landenburger's model
      for non-pregnant women.

PMID- 16966226
TI  - Creativity enhancement: possibilities for successful aging.
AB  - Successful aging is of growing importance in the U.S. Many researchers have
      explored the phenomenon using various approaches, yet we are still lacking
      practical guidelines on how to promote successful aging in older adults. The Roy
      Adaptation Model supports the promotion of adaptation to chronic health problems
      at a time when one's overall health may be declining and is a useful guide for
      understanding successful aging. Current literature also suggests that functional
      performance and creativity are important in order to age successfully. This study
      examined the relationships between functional performance, creativity, and
      successful aging within the context of the Roy Adaptation Model. Although
      creativity was not significantly predictive of successful aging, functional
      performance was a statistically significant predictor of a successful aging
      indicator, purpose in life. The study was a pretest-posttest experimental design
      investigating the effects of a creativity enhancement intervention in older
      adults. Although the intervention did not appear to increase creativity or
      successful aging, there were some statistically significant results and valuable
      findings about the possibilities for creativity enhancement.

PMID- 16966227
TI  - Schizophrenia and violence: the perspective of women.
AB  - Violence against women is a major public health problem. Women with a diagnosis
      of schizophrenia suffer higher rates of violence compared with women without
      mental illnesses. Little research has focused on what it means for women to live
      with schizophrenia and a history of violence. This interpretive phenomenological
      study identified three themes of schizophrenia and violence: Being Stigmatized,
      Foreclosing a Future of Possibilities, and Finding Meaning in Symptoms. The
      results suggest mental health professionals should assess women with diagnoses of
      schizophrenia for violence and provide opportunities for trauma stories to be
      heard. These listening types of patient-centered interventions may promote
      recovery.

PMID- 16966228
TI  - Fostering a culture of support in mental health settings: alternatives to
      traditional models of clinical supervision.
AB  - Clinical supervision [CS] for mental health nurses in inpatient settings in
      Sydney, Australia, is virtually nonexistent despite over a decade of discussion
      regarding its benefits to staff, patients, and organisations. Whilst there is
      general agreement about the merit of CS, its ad-hoc implementation and the use of
      models that do not correspond to the realities of the environment have led to its
      adoption being somewhat half-hearted. It is unsurprising then that there is an
      absence of achievable policy regarding CS making its integration into modern
      inpatient units even harder to attain. In this paper, we outline some pragmatic
      issues concerning CS and advocate for facility-specific professional development
      and support processes that incorporate succession planning opportunities. This we
      believe has the potential to promote professional behaviour, continuous learning
      and development, cohesive teamwork, and ultimately a change in culture regarding
      CS.

PMID- 16966229
TI  - Splitting the difference: the heroes and villains of mental health policy and
      nursing practice.
AB  - Drawing on psychodynamic and managerialist concepts, this paper explores possible
      consequences for patients and mental health nurses of the policy driven
      "splitting" of mental health service provision in the UK. Services and resources
      are now split for those with a severe and enduring mental illness and those with
      a common mental problem. We argue the damaging divisiveness in creating these two
      "political" groups makes determining how to meet the needs of individuals with
      common yet complex problems more difficult. The way in which an increased
      awareness and understanding of psychodynamic concepts can help the mental health
      nurse deal with such complexity is explored.

PMID- 16966230
TI  - The potential for utilizing inter-limb coupling in the rehabilitation of upper
      limb motor disability due to unilateral brain injury.
AB  - PURPOSE: Symmetry tendencies in human movement have generally been regarded as a
      constraint to upper limb motor performance. However, several recent studies have
      suggested that this phenomenon might be utilized in the rehabilitation of
      individuals with motor disability due to unilateral brain injury. In this paper
      the efficacy of such a rehabilitative approach is explored by reviewing: (i)
      examples of symmetry tendencies in healthy individuals, (ii) the potential
      neurophysiological mechanisms responsible for inter-limb coupling, and (iii)
      recent studies which have directly assessed the effects of inter-limb coupling on
      individuals with unilateral brain injury. METHOD: A thorough review of current
      published evidence was conducted utilizing various electronic search engines
      (Medline, PreMedline, Embase and Cinahl). Studies included those that focused on
      symmetry tendencies and/or inter-limb coupling in the upper limbs with a
      particular emphasis placed on studies of individuals with unilateral brain
      injury. RESULTS: Based on the current literature it seems that motor function of
      the affected upper limb in individuals with unilateral brain injury can be
      improved through a rehabilitation approach that incorporates inter-limb coupling.
      CONCLUSION: This approach should be considered as an adjunct to more common
      rehabilitation strategies with future research aimed at determining the most
      effective means of employing this paradigm.

PMID- 16966231
TI  - Pain, disability and rehabilitation practices. A phenomenological perspective.
AB  - PURPOSE: Rehabilitation experts and disabled people are faced with the question
      of pain on a daily basis. This is a complex phenomenon with various different
      aspects: physiological, social, cultural and personal experience. In this article
      the author focuses on the personal experience of pain, i.e., the way in which it
      is experienced by the person in question and how it changes that person, his/her
      body and life; the author refers to cases of people who became disabled following
      a road accident or a neuromuscular illness, and takes a phenomenonological and
      philosophical standpoint. METHOD: The article is based upon ethnographical
      observations made in three settings: assistance departments set up by an
      association, a wheelchair test centre and a rehabilitation centre. RESULTS AND
      DISCUSSION: The experience of pain has been described as a rupture of a person's
      relationship with the outside world leading to a loss in capacity. Rehabilitation
      enables this link to be rebuilt by focusing on the body and thus changing the way
      in which the person feels his/her body. CONCLUSIONS: This analysis highlights the
      importance of how pain is experienced and how it is taken into account in
      rehabilitation practices, whilst at the same time showing how rehabilitation
      changes this experience.

PMID- 16966232
TI  - Progressive resistance exercise for people with multiple sclerosis.
AB  - PURPOSE: This study aimed to determine if participation in a progressive
      resistance exercise (PRE) programme can: (1) increase the ability to generate
      maximal muscle force, (2) increase muscle endurance, (3) increase functional
      activity, and (4) improve overall psychological function of people with multiple
      sclerosis (MS). METHODS: A pre-post single group research design with a 4-week
      baseline familiarisation phase was used. Nine people (mean age 45.6 years, SD
      10.7) with MS attended a gymnasium three times over 4 weeks for familiarization.
      Participants then completed a twice-weekly 10-week PRE programme, with two sets
      of 10 - 12 repetitions of each exercise. Outcome measures of muscle strength (1RM
      for arms and legs), muscle endurance (repetitions at half 1RM), walking speed,
      the 2-min walk test (2MWT), a timed stairs test, and the impact of MS on physical
      and psychological function were taken at weeks 2, 4, and 14. RESULTS:
      Participants attended 94.3% (SD 8.2%) of the training sessions, with no adverse
      events. After accounting for baseline stability, significant improvements (P <
      0.05) were found in arm strength (14.4%), leg endurance (170.9%), fast walking
      speed (6.1%), and there was a trend for increased distance in the 2MWT (P =
      0.06). The perceived impact of MS on physical function was reduced (P = 0.02).
      CONCLUSIONS: Adults with MS benefited from a PRE programme by improving muscle
      performance and physical activities, without adverse events. These findings
      suggest that PRE may be a feasible and useful fitness alternative for people with
      mild to moderate disability due to MS.

PMID- 16966233
TI  - A qualitative analysis of a progressive resistance exercise programme for people
      with multiple sclerosis.
AB  - PURPOSE: This qualitative study explored the perceptions of adults with multiple
      sclerosis about the positive and negative effects of a progressive resistance
      strengthening programme; and identified factors that might facilitate or create
      barriers to participation. METHODS: Seven women and two men (mean age 45.6 years,
      SD 10.7) with multiple sclerosis participated in a 10-week gymnasium based
      progressive resistance strengthening programme held twice a week. Participants
      were interviewed at the end of the programme. The recorded interviews were
      transcribed and then independently coded by three researchers. From these codes,
      the main themes emerged. RESULTS: Reports about the programme were very positive
      with physical, psychological and social benefits noted. Most participants said
      that they had less fatigue as a result of the programme. Few negative outcomes
      were reported and these were minor such as aches and pains. Key extrinsic factors
      for programme completion were the leaders' encouragement and knowledge of
      exercise; and the group aspect of the programme. Key intrinsic factors were
      enjoyment, determination, seeing the signs of progress, and a previously held
      positive attitude about the benefits of exercise. CONCLUSIONS: The results of
      this study suggest that progressive resistance strength training is a feasible
      fitness option for some people with multiple sclerosis. Factors perceived to be
      important for programme completion suggest that choosing encouraging leaders with
      knowledge of exercise, and exercising in a group may contribute to programme
      success.

PMID- 16966234
TI  - Smoking rates and smoking cessation among individuals with multiple sclerosis.
AB  - PURPOSE: Adults with physical disabilities tend to smoke at higher rates than
      smokers in the general population. No study to date, however, has assessed
      smoking prevalence and cessation among individuals with multiple sclerosis (MS).
      Such information is critically needed because smoking is more deleterious for
      individuals with MS than for smokers without MS and increases MS risk. METHOD:
      Questionnaires were sent to 700 National Multiple Sclerosis Society Rhode Island
      Chapter members. RESULTS: Based on a 50% response rate, results demonstrated a
      15.2% current smoker prevalence rate, which is lower than USA and Rhode Island
      general adult population averages. Individuals who smoked, however, tended to be
      heavy smokers, consuming 20 - 30 cigarettes daily, and had been smoking 10 years
      or longer. Smokers varied in their interest in quitting but seemed confident in
      their ability to do so. Respondents reported that it was difficult to quit
      because smoking was pleasurable; smoking was helpful in coping with boredom and
      with having MS; withdrawal symptoms were unpleasant; and treatment for tobacco
      dependence was expensive. CONCLUSIONS: Efficacious smoking cessation
      interventions for smokers with MS should be developed to address a critical
      health need for a population of highly nicotine-dependent smokers who face
      numerous obstacles to quitting.

PMID- 16966235
TI  - Material handling performance of patients with chronic low back pain during
      functional capacity evaluation: a comparison between three countries.
AB  - PURPOSE: Functional Capacity Evaluations (FCEs) are batteries of tests designed
      to measure patients' ability to perform work-related activities. Although FCEs
      are used worldwide, it is unknown how patients' performances compare between
      countries or settings. This study was performed to explore similarities and
      differences in FCE performance of patients with chronic low back pain (CLBP)
      between three international settings that utilize the same FCE protocol. METHODS:
      Standardized FCEs were performed on three cohorts of patients with CLBP: A sample
      from an outpatient rehabilitation context in The Netherlands (n = 121), a
      Canadian sample in a Worker's Compensation context (n = 273), and a Swiss sample
      in an inpatient rehabilitation context (n = 170). Patients were undergoing FCE as
      part of their usual clinical care. Means and standard deviations of maximum
      performance on the FCE material handling items were calculated and differences
      compared using ANOVA. Multivariable linear regression was used to determine the
      relationship between country of origin and FCE performance while controlling for
      potential confounders including, age, sex, duration of back pain problems, and
      self-reported pain and disability ratings. RESULTS: Compared to the Dutch sample,
      the mean performance of patients in the Canadian and Swiss samples was
      consistently lower on all FCE items. This association remained statistically
      significant after controlling for potential confounders. CONCLUSIONS:
      Considerable differences were observed between settings in maximum weight handled
      on the various FCE items. Future FCE research should examine the effects of a
      number of potentially influential factors, including variability in evaluator
      judgements across settings, the evaluator-patient interaction and patients'
      expectations of the influence of FCE results on disability compensation.

PMID- 16966236
TI  - Validity of physical activity measures in ambulatory individuals with multiple
      sclerosis.
AB  - PURPOSE: The literature suggests that individuals with multiple sclerosis (MS)
      engage in less physical activity than non-diseased individuals. That conclusion,
      however, depends upon the validity of scores from measures of physical activity
      among the MS population. This study evaluated the validity of scores from two
      self-report surveys, a pedometer, and an accelerometer and during seven days of
      free-living conditions among individuals with MS. METHOD: Participants were 30
      individuals (28 females, two males) with an established definite diagnosis of MS.
      The participants wore a pedometer and a single-axis accelerometer during the
      waking hours of a 7-day period. After the 7-day period, participants returned to
      the lab and completed a self-administered physical activity questionnaire and
      then underwent a 7-day physical activity recall. RESULTS: There were strong
      correlations (a) between scores from the two self-report measures of physical
      activity and (b) between scores from the two objective measures of physical
      activity, and (c) weaker, but moderate-to-strong correlations between scores from
      the self-report and objective measures of physical activity. CONCLUSION: Our
      results support the quantification of physical activity among those with MS using
      validated self-report and objective measures.

PMID- 16966237
TI  - Participation of disabled children: how should it be characterised and measured?
AB  - PURPOSE: The aim of the paper is to explore the issues involved in measuring
      children's participation. METHOD: The concept of participation as encapsulated in
      the International Classification of Functioning, Disability and Health (ICF) is
      discussed as it applies to children. The essential components of any measure of
      children's participation are outlined, including participation essential for
      normal development and survival, leisure activities, and educational
      participation. Some existing instruments are briefly reviewed in terms of their
      coverage of the essential components and the adequacy of their approach to
      measurement. RESULTS: Key issues regarding the content of an adequate measure of
      participation include the need to consider the child's dependency on the family,
      and their changing abilities and autonomy as they grow older. Instruments may be
      most appropriate where they ask the child directly, implying use of visual as
      well as verbal presentation. Their focus should be on 'performance' such as
      whether and how often an activity is taken part in, and not incorporate degree of
      assistance within the measurement scaling. CONCLUSIONS: Currently available
      measures of children's participation all have some limitations in terms of their
      applicability across impairment groupings, whether the child can directly
      respond, and in the ICF components covered. The feasibility of developing
      measurement instruments of children's participation at different ages is
      discussed.

PMID- 16966238
TI  - "Marina-Trinkkur" and a few more modern-time hydrotherapeutic myths from the
      Kvarner region of NW Croatia.
AB  - PURPOSE: The present paper tries to address the rise and decay of the sea-water
      "cult" in regional health tourism in NW Croatia, concentrating upon and analysing
      more thoroughly the example of Marina, chemically processed sea water, an
      invention of Dr Geza Fodor, the Hungarian physician practicing in that part of
      Croatia. METHOD: The original documents and archived items related to the topic
      were examined. Furthermore, we investigated numerous communal bulletins and
      medical authorities' records of respective time. RESULTS: Our research showed
      that the sea-water baths, introduced thanks to the influence of balneologists
      (like J. Glax), and "drinking cures" (advocated by M.-J. Ortel, for instance)
      were surprisingly popular not only among tourists of the time, but also among the
      physicians that used them extensively for therapeutical purposes. These baths and
      "drinking cures" enriched and completed the medical offer of the resorts
      regardless of their sometimes dubious effectiveness. CONCLUSIONS: This simple
      distilled sea-water preparation, advertised as a real panacea, demonstrates a
      paradigm that elucidates the mentality of physicians, merchants, and
      patients/consumers of the time.

PMID- 16966239
TI  - Development of cerebral lateralisation for recognition of emotions in chimeric
      faces in children aged 5 to 11.
AB  - In contrast to research into the development of language laterality, there has
      been relatively little research into the development of lateralisation of
      emotional processing. If language lateralisation begins in childhood and is
      complete by puberty (Lenneberg, 1967) it seems reasonable that the lateralisation
      of the perception of emotions might also occur during this period. In this study
      a split field chimeric faces test using the six universal facial expressions
      proposed by Ekman and Friesen (1971), an emotion in the eyes test, and a
      situational cartoon test were administered to three groups of children aged 5/6,
      7/8, and 10/11. No overall hemispace advantage was seen for the 5/6-year-old
      group, but by the age of 10/11 a clear left hemispace advantage (right
      hemisphere) was found for all six emotions. Such a pattern is comparable to a
      previous study that made use of adults on this task (Workman, Peters, & Taylor,
      2000b). Moreover, a significant positive correlation between a child's ability to
      recognise emotions in cartoon situations and their left hemispatial advantage
      score was uncovered. Finally, a significant positive correlation between a
      child's ability to recognise emotions in the eyes of others and their left
      hemispatial advantage score was also uncovered. These findings are taken as
      evidence that there may be a relationship between the development of emotional
      processing in the right hemisphere and a child's emerging ability to perceive or
      attend to the emotional states of others. Results are discussed in relation to
      the child's development of a theory of mind.

PMID- 16966240
TI  - Heritability and linkage analysis of hand, foot, and eye preference in Mexican
      Americans.
AB  - Functional lateralities are of interest due to their relationship with cerebral
      lateralisation and language development. However, genes influencing sidedness
      remain elusive. We measured direction and consistency of hand, foot, and eye
      preference in 584 Mexican-Americans from families participating in the San
      Antonio Family Diabetes/Gallbladder Study. Using maximum-likelihood-based
      variance components methods, we estimated weak (.11 <or= h2<or=.17) but
      significant heritability for foot preference, eye preference, several hand
      preferences (writing, drawing, throwing, using scissors, using spoon, striking
      match), and a composite hand preference trait. Self-reported handedness was
      significantly heritable (h2=.57), whereas hand preference for opening a box or
      using a toothbrush or knife was not. Many trait pairs had significant genetic
      correlations, and all had significant environmental correlations. Using genome
      wide multipoint linkage screens using 382 highly informative autosomal STR
      markers, we identified suggestive linkage signals for drawing (LOD 2.10) and
      writing (LOD 2.00) hand preference on chromosome 12q21-23, in the region flanked
      by markers D12S1300 and PAH. A suggestive signal (LOD 2.46) for eye preference
      occurred on chromosome 22pter, near marker D22S420. No obvious candidate genes
      occur in these regions. Our results indicate that genes are an important
      component of side preferences, and suggest chromosomal regions for further
      investigation.

PMID- 16966241
TI  - Language and visuospatial impairment in a case of crossed aphasia.
AB  - Crossed aphasia in dextrals (CAD) constitutes an interesting model for
      understanding the lateralisation and interaction of language with other cognitive
      functions in the brain. The authors present a study of a right-handed patient
      with Wernicke's aphasia following a right hemisphere cerebrovascular accident,
      who also had impairment in visuospatial skills. Although the patient presented a
      remarkable improvement in language symptoms on longitudinal follow-up, the
      combination of linguistic, visuospatial, and attentional impairments ultimately
      resulted in a persisting inability to perform complex tasks. The study of mild
      residual disturbances can improve our understanding of the interaction of
      language with other cognitive functions, going some way towards explaining the
      particular features found in CAD.

PMID- 16966243
TI  - Was Alexander the Great left-handed?
AB  - No evidence, literary or pictorial, exists from antiquity to indicate that
      Alexander the Great was left-handed. Instead classical representations of
      Alexander show him as right-handed.

PMID- 16966242
TI  - The role of structural facial asymmetry in asymmetry of peak facial expressions.
AB  - Asymmetric facial expression is generally attributed to asymmetry in movement,
      but structural asymmetry in the face may also affect asymmetry of expression.
      Asymmetry in posed expressions was measured using image-based approaches in
      digitised sequences of facial expression in 55 individuals, N=16 men, N=39 women.
      Structural asymmetry (at neutral expression) was higher in men than women and
      accounted for .54, .62, and .66 of the variance in asymmetry at peak expression
      for joy, anger, and disgust expressions, respectively. Movement asymmetry
      (measured by change in pixel values over time) was found, but was unrelated to
      peak asymmetry in joy or anger expressions over the whole face and in facial
      subregions relevant to the expression. Movement asymmetry was negatively related
      to peak asymmetry in disgust expressions. Sidedness of movement asymmetry
      (defined as the ratio of summed movement on the left to movement on the right)
      was consistent across emotions within individuals. Sidedness was found only for
      joy expressions, which had significantly more movement on the left. The
      significant role of structural asymmetry in asymmetry of emotion expression and
      the exploration of facial expression asymmetry have important implications for
      evolutionary interpretations of facial signalling and facial expressions in
      general.

PMID- 16966244
TI  - The modern mythology of the left-handedness of Alexander the Great.
AB  - The prevalent modern suggestion that Alexander the Great was left-handed probably
      derives from Michael Barsley's (1966) book, Left-handed man is a right-handed
      word, perhaps by mutation from as earlier story cited by Wile in 1934 from a 17th
      century Rabbirical exegesis, which said that Alexander discovered a country where
      all the inhabitants were left-handed. That itself may derive in part from the
      medieval Hebrew Book of Jossippon, which mentions Alexander talking of the
      superiority of the left hand and of how "kings stemming from the tribe of kings
      are left-handed".

PMID- 16966245
TI  - Kissing laterality and handedness.
AB  - Kissing behaviour was observed between kissing couples: about 80% turned their
      heads to the right to kiss. To remove the influence of one kissing partner upon
      the other, kissing behaviour was also observed between participants and a
      symmetrical doll's face: about 77% turned their heads to the right to kiss. There
      was no significant difference in handedness between right- and left-kissers: both
      groups were predominantly right-kissers. It is thought that motor bias rather
      than emotive bias influences kissing behaviour.

PMID- 16966247
TI  - Autoimmunity and chronic lymphocytic leukemia.

PMID- 16966248
TI  - Autoimmunity in CLL: grave consequences of gravidity?

PMID- 16966249
TI  - Toxicity of high dose BCNU: how much is too much?

PMID- 16966250
TI  - Photopheresis versus transimmunization?

PMID- 16966251
TI  - Treatment strategies for pediatric nodular lymphocyte predominant Hodgkin's
      lymphoma.

PMID- 16966252
TI  - When is myeloma, myeloma?

PMID- 16966253
TI  - The relevance of information generated by in vitro experimental models to
      clinical doxorubicin cardiotoxicity.

PMID- 16966254
TI  - TRAIL, caspases and maturation of normal and leukemic myeloid precursors.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) is a
      membrane-bound cytokine molecule that belongs to the family of tumor necrosis
      factor (TNF). Members of this family share diverse biological effects, including
      induction of apoptosis and/or promotion of cell survival. Identification of TRAIL
      has generated considerable enthusiasm for its ability to induce apoptotic cell
      death in a variety of tumor cells, by engaging the death receptors TRAIL-R1/DR4
      and TRAIL-R2/DR5, while sparing most normal cells. Beside its anticancer
      activity, several studies have suggested a role for endogenously expressed TRAIL
      in hemopoiesis. In this review, we summarize the knowledge about the different
      lineage-specific roles of TRAIL and its receptors in hemopoiesis regulation.
      Moreover, the complex interplay among the signaling pathways triggered by
      TRAIL/TRAIL-receptors in myeloid cells is discussed in some detail.

PMID- 16966255
TI  - CCR6 regulates the function of alloreactive and regulatory CD4+ T cells during
      acute graft-versus-host disease.
AB  - The chemokine receptor CCR6 is expressed by CD4+ T cell effector/memory and
      regulatory effector/memory (TREM) subsets. Here we show that CCR6 modulates graft
      versus-host-disease (GVHD) responses in both alloreactive CD4+ T effector cells
      and regulatory T (Treg) cells. Mortality and morbidity due to acute GVHD were
      drastically reduced and delayed when naive T cells were derived from CCR6
      deficient donor mice. This deficiency also affected the suppressive ability of
      Treg cells in GVHD. CCR6-/- Treg cells were able to suppress T cell proliferation
      in vitro, but their in vivo capacity to downregulate target tissue damage induced
      by naive wild type (WT) T cells was impaired. The data demonstrate a requirement
      for CCR6 in CD4+ T cell function in GVHD, in both effector and regulatory cell
      subsets.

PMID- 16966256
TI  - Sex differences in incidence and outcome of chronic lymphocytic leukemia
      patients.
AB  - Observational studies have consistently reported a reduced incidence and superior
      survival for female patients with chronic lymphocytic leukemia (CLL). These
      results were corroborated by different national cancer database reports and
      confirmed in recent prospective trials. Whether improved survival for women is
      attributable to increased comorbidities in men, better response and/or tolerance
      of therapy in women or an intrinsic difference in the molecular biology of the
      disease (or a combination thereof) is unknown. It is through prospective trials
      that evaluate known molecular, genetic and clinical prognostic predictors that
      one will better understand these differences and determine whether treatment
      should be tailored to biological clinical profiles or more to sex.

PMID- 16966257
TI  - The influence of pregnancy on the development of autoimmunity in chronic
      lymphocytic leukemia.
AB  - To examine whether pregnancy influences the development of autoimmunity in
      chronic lymphocytic leukemia (CLL), we studied 591 consecutive CLL patients (202
      post-menopausal women and 389 men). The mean observation time for all patients
      was 3.8 years, corresponding to approximately 2200 person-years of follow-up.
      Autoimmune manifestations were analyzed in 194 women with known obstetric history
      and known number of long-term sexual partners, and in the 389 male CLL patients
      for comparison. One hundred and fifty-nine of the CLL patients exhibited
      autoimmune manifestations, 38% in females and 21% in men. In female CLL patients,
      the frequency of autoimmunity and the number of pregnancies and the number of
      partners were strongly correlated. Each of the major autoimmune types
      approximately doubled in frequency for each additional pregnancy. The impact of
      pregnancy on expressed autoimmunity increased with each additional sexual partner
      (the odds of autoimmunity increased 11 times with each long-term sexual partner).
      The average numbers of pregnancies in female CLL patients with and without
      autoimmunity were 4.92 and 2.24, respectively (P < 0.001). Coombs' positive
      autoimmune anemia, a gastric ulcer with parietal cell autoantibodies and
      idiopathic thrombocytopenic purpura were equally common in women and men, whereas
      autoimmune thyroiditis, Sjogren's syndrome, rheumatoid arthritis and systemic
      lupus erythematosus were seen in higher rates in women than in men. The spectrum
      of autoimmunity suggests that pregnancy-related alloimmunization may be involved
      in the development of autoimmunity in CLL.

PMID- 16966258
TI  - Morbidity and transplant-related mortality of CBV and BEAM preparative regimens
      for patients with lymphoid malignancies undergoing autologous stem-cell
      transplantation.
AB  - CBV and BEAM are the two most frequently used regimens for patients with lymphoma
      undergoing autologous hematopoietic stem-cell transplantation (ASCT). This study
      compared their morbidity and transplant-related mortality (TRM) in 113 patients
      with non-Hodgkin's lymphoma (69) and Hodgkin's disease (44) undergoing ASCT
      between 1990 - 2004. CBV (cyclophosphamide, 6000 mg m(-2); VP-16, 750 mg m(-2);
      and high-dose BCNU, 800 mg m(-2)) was administered to 75 patients and 38 received
      BEAM (BCNU, 300 mg m(-2); VP-16, 800 mg m(-2); cytarabine, 800 mg m(-2);
      melphalan, 140 mg m(-2)). Patients in the BEAM group had a significantly higher
      median age (p = 0.002) and were more heavily treated before ASCT (p = 0.003).
      More patients showed active disease at transplant in the BEAM group (p = 0.04).
      Sinusoidal obstruction syndrome (SOS) was more frequent in the CBV group (11% vs
      0%, p = 0.048). There were 20 (18%) transplant-related deaths, 18 in the CBV and
      two in the BEAM group. Infectious complications (12 patients, seven with
      pneumonia) and SOS (four) were the most frequent causes of death. The cumulative
      incidences of TRM were 25% in the CBV and 7% in the BEAM group (p = 0.02). CBV
      thus produced a higher incidence of SOS and TRM than BEAM in this series.

PMID- 16966259
TI  - Transimmunization for cutaneous T cell lymphoma: a Phase I study.
AB  - Extracorporeal photochemotherapy (ECP) is a widely used immunotherapy for
      cutaneous T cell lymphoma (CTCL). It involves four sequential steps: conversion
      of blood monocytes into dendritic antigen presenting cells (DC) by repetitive
      adherence and disadherence to plastic surface; reinfusion of the new DC; presumed
      in vivo loading of the new DC with apoptotic malignant leukocytes; and expansion
      of the anti-tumor CD8 T cell pool. To assess the safety of a methodology designed
      to increase ex vivo contact between the apoptotic malignant cells and new DC
      prior to reinfusion, a single-center, open-label Phase I clinical study of a
      revised procedure--referred to as "Transimmunization"--was conducted in CTCL
      patients. Twenty-seven subjects were treated monthly for 3 to 5 months, alone or
      in combination with electron beam therapy. For those receiving Transimmunization
      alone, there was an overall diminution in infiltrative lesions in eleven (55%) of
      twenty patients. In the twelve leukemic CTCL patients, there was a significant
      mean reduction of 50.1% in the circulating malignant cells, as determined with
      family-specific anti-T cell receptor Vbeta monoclonal antibodies (P <or= 0.021).
      Because this therapy permits the synchronous induction and tumor loading of DC,
      with minimal toxicity, Transimmunization may merit further investigation in CTCL
      and other malignancies.

PMID- 16966260
TI  - High relapse rate in children with non-advanced nodular lymphocyte predominant
      Hodgkin's lymphoma (NLPHL or nodular paragranuloma) treated with chemotherapy
      only.
AB  - Nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) is a rare variant of
      Hodgkin's lymphoma (HL) in children. Since specific immunohistochemical staining
      has become available, NLPHL can be separated from classical Hodgkin's lymphoma
      (cHL) more accurately. Scarce information is available about pediatric NLPHL
      treated with chemotherapy only. Therefore, clinical characteristics, treatment,
      response and outcome of seven pediatric NLPHL patients, median age 9.2 years
      (range 7.5 - 14.2 years), diagnosed between 1986 - 2003 among 58 HL patients,
      uniformly treated in a single center with chemotherapy only, were evaluated. The
      median follow-up time was 4.2 years (range 2.1 - 10.2 years). NLPHL patients were
      stage I (n = 5), II (n = 2), whereas cHL, median age 11.4 years (range 3.3 - 15.9
      years), were stage I (n = 8), II (n = 17), III (n = 9), IV (n = 1). Upfront
      treatment of NLPHL patients consisted of six courses of epirubicin, bleomycin,
      vinblastine and dacarbazine (EBVD) without radiotherapy, whereas cHL patients
      received six courses of EBVD (n = 14) or 4 - 6 courses of EBVD/MOPP (mitoxin,
      oncovin, procarbazine, prednison; n = 21). Chemotherapy was used as primary
      treatment thereby aiming to avoid radiotherapy with potential serious side
      effects to growing jaws and thyroid. All seven patients reached complete
      remission (CR). Four patients relapsed, of which three locally. These three were
      salvaged with second-line chemotherapy without radiation therapy (RT) and are in
      second CR. One patient relapsing with stage III disease was salvaged by EBVD/MOPP
      followed by autologous BMT and is also in second CR for 36 months. The event-free
      survival (EFS) is 43% and overall survival (OS) 100%. This study shows that apart
      from histology, immunohistochemistry (ICH) is required for diagnosing NLPHL.
      Moreover, it illustrates that although cure of pediatric NLPHL is feasible with
      chemotherapy only, high dosages of cytotoxic drugs are necessary as salvage
      treatment in a relatively high proportion of patients after relapse.

PMID- 16966261
TI  - Sequential doxorubicin and topotecan in relapsed/refractory aggressive non
      Hodgkin's lymphoma: results of CALGB 59906.
AB  - Topoisomerase enzymes are critical components of genomic replication and function
      to minimize torsional stress on DNA. Sequential administration of a topoisomerase
      II inhibitor followed by a topoisomerase I inhibitor is potentially synergistic
      due to increased target enzyme levels. Patients with relapsed or refractory
      aggressive non-Hodgkin's lymphomas (NHL) were eligible for this phase II study of
      doxorubicin 25 mg/m2 intravenous (IV) on day 1 and topotecan 1.75 mg/m2/day IV on
      days 3 - 5, every 21 days. The trial objectives included the overall response
      rate, progression-free survival, and toxicity. Twenty-six patients were enrolled
      and 25 patients are assessable for toxicity and response. The median age was 58
      (range 23 - 74) years. The patients had received a median of two (range one to
      five) prior regimens, including five patients with a prior stem cell transplant.
      Five patients (20%, 95% confidence interval 0.07, 0.42) responded with two (8%)
      complete remissions and three (12%) partial remissions; an additional four (16%)
      patients had stable disease. Both patients achieving a complete remission had
      Burkitt's lymphoma. There were no treatment-related deaths. In conclusion, the
      combination of doxorubicin and topotecan is well tolerated and has modest
      activity in relapsed/refractory NHL, with occasional patients having a prolonged
      remission. The activity in Burkitt's lymphoma should be investigated further.

PMID- 16966262
TI  - Hodgkin's lymphoma in the elderly: the results of 10 years of follow-up.
AB  - Elderly patients with Hodgkin's lymphoma carry a worse prognosis than younger
      patients because of a higher incidence of advanced stages, a worse performance
      status and the intolerance of full-dose curative treatment. A retrospective
      analysis of patients treated at our institution was performed. Our retrospective
      study summarizes the treatment results for 52 Hodgkin's lymphoma patients aged
      older than 60 years between 1973 and 1993. These patients were treated with
      combination of less toxic chemotherapy schedule (cyclophosphamide, vincristine,
      procarbazine and prednisone) and/or involved-field radiotherapy. The aim was to
      maintain an acceptable quality of life in spite of lower remission rate. The 5-
      and 10-year overall survival rates were 48% and 33%, respectively. We found two
      independent prognostic factors for overall survival: (i) stage of the disease and
      (ii) accomplishment of the treatment. Combined modality treatment yielded better
      results than chemotherapy. Tolerance of the treatment was acceptable. The present
      study demonstrates that a combination of mild chemotherapy with limited
      radiotherapy is a feasible way of treating elderly patients with Hodgkin's
      lymphoma.

PMID- 16966263
TI  - Molecular analysis of light-chain switch and acute lymphoblastic leukemia
      transformation in two follicular lymphomas: implications for lymphomagenesis.
AB  - We observed novel transformations of follicular lymphoma (FL), first, a switch in
      immunoglobulin (Ig) light chain, and second, transformation of FL to acute
      lymphoblastic leukemia (ALL). Each set of tumors shared a common clonal origin,
      as demonstrated by expression of identical, unique CDR IIIH sequences, shared
      somatic mutations in JH, and identical bcl-2 translocation breakpoints of
      microdissected ALL cells. Molecular analysis of lambda V-gene expression
      demonstrated lambda-bearing cells in the original kappa tumor, while expansion of
      the lambda subclone at relapse occurred after active immunotherapy targeting the
      Ig receptor. These exceptional cases are compatible with a more contemporary
      model of lymphomagenesis in which critical events originate from genetic
      mechanisms which normally occur in germinal center (GC) B cells and challenge the
      current paradigm of parallel generation of subclones from an early, pre-GC
      precursor. It is also possible that the outgrowth of these variants was a
      consequence of immunoselection.

PMID- 16966264
TI  - Medical costs associated with non-Hodgkin's lymphoma in the United States during
      the first two years of treatment.
AB  - OBJECTIVES: To determine the direct costs of medical care associated with
      aggressive and indolent non-Hodgkin's lymphoma (NHL) in the United States; to
      show how costs for aggressive NHL change over time by examining costs related to
      initial, secondary and palliative treatment phases; and to evaluate the economic
      consequences of treatment failure in aggressive NHL. PATIENTS AND METHODS: A
      retrospective cohort analysis of 1999 - 2000 direct costs in newly diagnosed NHL
      patients and controls (subjects without any cancer) was conducted using the
      MarketScan medical and drug claims database of large employers across the United
      States. Treatment failure analysis was conducted for aggressive NHL patients, and
      was defined by the need for secondary treatment or palliative care after initial
      therapy. Cost of treatment failure was calculated as difference in regression
      adjusted costs between patients with initial therapy only and patients
      experiencing initial treatment failure. RESULTS: Patients with aggressive (n =
      356) and indolent (n = 698) NHL had significantly greater health service
      utilization and associated costs (all P < 05) than controls (n = 1068 for
      aggressive, n = 2094 for indolent). Mean monthly costs were 5871 dollars for
      aggressive NHL vs. 355 dollars for controls (P < 0001) and 3833 dollars for
      indolent NHL vs. 289 dollars for controls (P < 0001). The primary cost drivers
      were hospitalization (aggressive NHL = 44% of total costs, indolent NHL = 50%)
      and outpatient office visits (aggressive NHL = 39%, indolent NHL = 34%). For
      aggressive NHL, mean monthly initial treatment phase costs (10,970 dollars) and
      palliative care costs (9836 dollars) were higher than costs incurred during
      secondary phase (3302 dollars). The mean cost of treatment failure in aggressive
      NHL was 14,174 dollars per month, and 85,934 dollars over the study period.
      CONCLUSION: The treatment of NHL was associated with substantial health care
      costs. Patients with aggressive lymphomas tended to accrue higher costs, compared
      with those with indolent lymphomas. These costs varied over time, with the
      highest costs occurring during the initial treatment and palliative care phases.
      Treatment failure was the most expensive treatment pattern. New strategies to
      prevent or delay treatment failure in aggressive NHL could help reduce the
      economic burden of NHL.

PMID- 16966265
TI  - High dose sequential chemotherapy and autologous stem cell transplantation in
      patients with relapsed/refractory lymphoma.
AB  - Although high-dose chemotherapy followed by autologous stem cell transplantation
      (ASCT) has become the standard approach for patients with relapsed/refractory
      Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL), more than 50% of patients
      will experience relapse following ASCT. High-dose sequential chemotherapy (HDSC)
      can intensify the conventional salvage treatment and improve the outcome of ASCT
      by maximal debulking of the tumor load with the use of non-cross resistant drugs,
      each at their maximal tolerated doses. We conducted a phase II study in 40
      patients with relapsed/refractory HD (n = 18) and NHL (n = 22) using HDSC
      followed by ASCT. Only patients sensitive to salvage chemotherapy were eligible
      for the protocol, consisting of three phases. Phase I consisted of
      cyclophosphamide (4.5 g/m2) followed by G-CSF and peripheral blood stem cell
      (PBSC) collection. Phase II consisted of etoposide (2 g/m2). The transplant phase
      consisted of mitoxantrone (60 mg/m2) and melphalan (180 mg/m2) followed by PBSC
      infusion. Eleven out of nineteen patients with B-cell lymphoma received
      rituximab. Prior to HDSC, 45% of the patients were in complete remission (CR) and
      55% were in partial remission (PR). After completion of all phases of the
      protocol, 35 out of 39 evaluable patients achieved CR (90%) and this was durable
      in 30 (75%) patients with a projected progression-free survival (PFS) rate at 4
      years of 71.7%. Treatment-related mortality rate at day +100 was 2.5% (n = 1). At
      a median follow-up of 32 months (range, 3 - 61), nine patients
      relapsed/progressed and eleven patients died. The estimated 4-year PFS and
      overall survival (OS) were 72.2% and 47.6% in HD patients and 70.3% and 69.4% in
      NHL patients, respectively. Factors predicting OS were response to conventional
      salvage therapy and stage prior to salvage therapy. When compared to patients
      achieving PR, patients who attained CR prior to HDSC had a significantly higher
      probability of 4-year OS (78.4% vs 31.3%, p = 0.02). Three prognostic subgroups
      were defined according to the score determined by stage prior to initiation of
      salvage chemotherapy, remission duration prior to salvage (refractory/early
      relapse vs. late relapse) and response to salvage. Prognostic score was found to
      predict OS, PFS and event free survival (EFS). In conclusion, HDSC followed by
      ASCT is an effective salvage therapy with acceptable toxicity, allowing further
      consolidation of response attained by conventional salvage therapy.

PMID- 16966266
TI  - Macrofocal multiple myeloma in young patients: a distinct entity with favorable
      prognosis.
AB  - There are limited reports of young patients with multiple myeloma (MM) who
      presented with multiple lytic bone lesions but without intervening infiltration
      of bone marrow, a pattern consisting of macrofocal MM. In order to clearly define
      the clinical and laboratory features and outcome of such patients, a
      retrospective analysis was performed of symptomatic patients with MM <or=40 years
      of age at diagnosis who received primary treatment over a 20-year period. Ten of
      51 patients fulfilled the criteria of macrofocal MM. When compared to patients
      with typical MM, patients with macrofocal pattern were less anemic, none had
      hypercalcemia, renal impairment, elevated serum LDH or stage 3 according to the
      International Staging System (ISS). Patients with macrofocal MM usually had
      preserved the uninvolved immunoglobulins. An objective response to primary
      treatment was noted in 55% of patients with macrofocal MM and in 50% of patients
      without this pattern. The median survival of patients with typical MM was 57
      months and is projected to exceed 8 years in patients with macrofocal MM (p =
      0.087). With macrofocal MM despite multiple lytic bone lesions, patients have
      features of low tumor burden and improved survival when compared with young
      patients with typical MM.

PMID- 16966267
TI  - De novo acute myeloid leukemia in adults younger than 60 years of age:
      socioeconomic aspects and treatment results in a Brazilian university center.
AB  - We retrospectively studied the outcomes of adults with de novo acute myeloid
      leukemia treated in a reference center in Brazil and analyzed the association
      with the human development index (HDI) of the United Nations used as a
      socioeconomic factor. Among 123 patients, 46 (37%) died during induction, 65
      (53%) reached complete remission and 45 (37%) received high-dose cytarabine
      (Hidac) consolidation. The 5-year overall survival and leukemia-free survival
      (LFS) were 17 and 26%, respectively, for all patients and 36 and 30%,
      respectively, for those receiving Hidac. In multivariate analysis, an HDI <0.660
      was associated with a lower probability to receive Hidac (P = 0.001), a trend for
      higher mortality in remission induction (P = 0.062) and a decreased LFS (P <
      0.0001). However, it was not associated with outcomes for patients receiving
      Hidac. In conclusion, survival for patients who received Hidac consolidation is
      satisfactory; however, socioeconomic factors may have selected patients to
      receive intensive Hidac consolidation.

PMID- 16966268
TI  - IgM multiple myeloma: report of four cases and review of the literature.
AB  - The differential diagnosis between multiple myeloma (MM) and Waldenstrom's
      macroglobulinemia (WM) is generally well defined. Consistent with a diagnosis of
      MM is the presence of a non-IgM monoclonal gammopathy associated to multiple
      osteolytic lesions and plasma cell infiltration of the bone marrow.
      Characteristic of WM is the presence of an IgM monoclonal gammopathy associated
      to lymphoadenopathy, hepatosplenomegaly, anemia and hyperviscosity syndrome in
      the presence of a monoclonal lymphoplasmacytoid proliferation in the bone marrow.
      Nonetheless, few cases of IgM myeloma have been reported that display clinico
      pathologic features intermediate between MM and WM. Here, this study describes
      four of 317 (1.2%) patients with an IgM monoclonal gammopathy in whom the
      morphologic and clinical features were consistent with a diagnosis of IgM
      myeloma.

PMID- 16966269
TI  - Immune parameters in multiple myeloma patients: influence of treatment and
      correlation with opportunistic infections.
AB  - The present study evaluated cellular and humoral immune parameters in myeloma
      patients, focusing on the effect of treatment and the risk of opportunistic
      infections. Peripheral blood lymphocyte subsets and serum levels of nonmyeloma
      immunoglobulins (Ig) were analysed in 480 blood samples from 77 myeloma patients.
      Untreated myeloma patients exhibited significantly reduced CD4+/45RO+, CD19+,
      CD3+/HLA-DR+, and natural killer (NK) cells, as well as nonmyeloma IgA, IgG and
      IgM. Conventional-dose chemotherapy resulted in significantly reduced CD4+ and
      even further decline of CD4+/CD45RO+ and CD19+ cells, most notably in relapsed
      patients. Additional thalidomide treatment had no significant effects on these
      parameters. Following high-dose chemotherapy (HD-CTX), prolonged
      immunosuppression was observed. Although CD8+, NK, CD19+ and CD+/CD45RO+ cells
      recovered to normal values within 60, 90, 360 and 720 days, respectively, CD4+
      counts remained reduced even thereafter. Nine opportunistic infections were
      observed, including five cytomegalovirus (CMV) diseases, one Pneumocystis carinii
      pneumonia (PCP) and three varicella zoster virus infections with CMV diseases and
      PCP occurring exclusively after HD-CTX. Opportunistic infections were correlated
      with severely reduced CD4+, as well as CD4+/CD45RO+ and CD19+ counts. Thus,
      myeloma patients display cellular and humoral immunodeficiencies, which increase
      following conventional as well as HD-CTX, and constitute an important
      predisposing factor for opportunistic infections.

PMID- 16966270
TI  - Marrow irradiation with high-dose 153Samarium-EDTMP followed by chemotherapy and
      hematopoietic stem cell infusion for acute myelogenous leukemia.
AB  - In four patients, aged 15 - 20 years, with high-risk acute myeloid leukemia
      (AML), high-dose samarium 153-labelled ethylenediaminetetramethylenephosphonate
      (153Sm-EDTMP) was used for targeted marrow irradiation before preparative
      chemotherapy conditioning regimens and allogeneic (three patients) or autologous
      (one patient) hematopoietic stem cell transplantation. The dose of 153Sm-EDTMP
      was 703 MBq/kg (n = 1) or 1110 MBq/kg (n = 3). No side-effects occurred during
      the 30-min infusion of 153Sm-EDTMP. Samarium - melphalan regimens were given to
      three patients; one had 153Sm-EDTMP - busulfan + cyclophosphamide. Total body
      radioactivity was below the 133 MBq safe limit before infusion of stem cells (day
      14 after 153Sm-EDTMP). No hemorrhagic cystitis, nephrotoxicity or serious
      infections occurred. Leukocyte engraftment (white blood cell count >0.5 x
      10(9)/l) occurred between 12 and 23 days after stem cell infusion (mean of 17
      days). Complete cytogenetic and morphologic remission of AML was evident on
      follow-up marrow aspirate and biopsy specimens from all patients. In two of the
      four study patients, the disease remains in complete remission and the patients
      have an excellent quality of life (Eastern Cooperative Oncology Group performance
      status 0; no medications) and no organ toxicity more than 2 years and more than 4
      years, respectively, after their blood and bone marrow transplantations. Thus, in
      adolescents and adults, 153Sm-EDTMP may provide a relatively simple and effective
      means for using irradiation to eliminate AML within the marrow.

PMID- 16966271
TI  - Feasibility of autologous peripheral blood stem cell transplantation in elderly
      patients with acute myeloid leukemia.
AB  - Most studies showing that autologous stem cell transplantation (ASCT) is feasible
      in older patients with acute myeloid leukemia (AML) referred to highly selected
      patients considered as eligible after complete remission (CR) achievement and
      bone marrow or peripheral blood stem cell (PBSC) collection. This study evaluated
      the feasibility of ASCT from 155 consecutive AML patients aged over 60 years
      (median age 72 years, range 61 - 94) programmed to receive ASCT by using PBSCs
      after CR achievement. Overall, 90 out of 155 patients (58%) were judged as
      eligible for aggressive chemotherapy and 45 (50%) achieved CR. Among these, 36
      (80%) received consolidation and 32 (89% of consolidated) were monitored for PBSC
      mobilization. A successful collection was registered in 25/32 patients (78% of
      monitored). Finally, 20 patients received ASCT. Reasons for not autografting five
      mobilizing patients included relapse pre-ASCT, toxicity, and refusal. Median
      survival was 4 months for the whole patient population and 19 months for patients
      actually autografted. Overall, 20 out of 90 patients accrued into intensive
      chemotherapy (22%) and 20 out of the entire patient population (13%) underwent
      ASCT. It is concluded that APBSCT can result in an improvement of therapeutic
      results in AML of the elderly, but it is feasible in a minority of selected
      patients.

PMID- 16966272
TI  - A precise pharmacodynamic study showing the advantage of a marked reduction in
      cardiotoxicity in continuous infusion of doxorubicin.
AB  - We have already shown that the antileukemic activity of daunorubicin that had
      been reported to be dependent on the area under the concentration - time curve
      (AUC) was actually peak concentration (Cmax) dependent. The antitumor activity of
      doxorubicin (DXR) has also been reported to be dependent on AUC, whereas its
      cumulative cardiotoxicity has been reported to be Cmax dependent. In this study,
      we evaluated whether the antileukemic and cardiotoxic effects of DXR were AUC or
      Cmax dependent, and compared their cytotoxic effects, utilizing the computer
      controlled in vitro pharmacokinetic simulation system or a conventional culture
      system for a leukemic cell line and measuring the intracellular ATP amount or the
      proportion of beating cells for the cardiotoxicity. In leukemic cells, the
      cytotoxic rate decreased as the simulated infusion time or exposure time
      increased with the same AUC value in the simulation and conventional culture
      system (P < 0.05 and <0.01, respectively). The intracellular ATP and proportion
      of beating cells also increased with prolonged DXR exposure time with the same
      constant concentration - time product value (P < 0.05 and <0.0001, respectively)
      in heart cells. These results indicated that both the antileukemic effects and
      the cardiotoxicity were Cmax dependent. However, a comparison of the two showed
      that cardiotoxicity was more Cmax dependent than the antileukemic effect. These
      results suggested that the continuous infusion treatment schedule of DXR may have
      the clinical advantage of reducing cardiotoxicity more markedly than the
      antileukemic effect.

PMID- 16966273
TI  - A prospective study on chemotherapy-induced hepatitis B virus reactivation in
      chronic HBs Ag carriers with hematologic malignancies and pre-emptive therapy
      with nucleoside analogues.
AB  - Chemotherapy-induced hepatitis B virus (HBV) reactivation is a serious problem in
      chronic HBV carriers with hematologic malignancies. In 12 patients with
      hematologic malignancies, we performed a prospective study to determine the
      effectiveness of nucleoside analogues in the pre-emptive therapy of chemotherapy
      induced HBV reactivation. HBV reactivation occurred in seven patients (58.3%)
      whereas five of the seven patients (71%) responded to nucleoside analogue
      therapy. HBV reactivation-related acute liver failure and death was not observed
      in the present study. All five patients with chronic lymphocytic leukemia (CLL)
      experienced chemotherapy-induced HBV reactivation regardless of the chemotherapy
      regimen. Therefore, we suggest that CLL carries a significant risk of
      chemotherapy-induced HBV reactivation. The pre-emptive therapy of chemotherapy
      induced HBV reactivation appears to be safe, based on the results of this pilot
      study. Pre-emptive therapy enables the definition of high-risk patients who
      cannot be identified by primary prophylaxis.

PMID- 16966274
TI  - Pleocytosis after hemopoietic stem cell transplantation.
AB  - Frequency and clinical significance of cerebrospinal fluid (CSF) pleocytosis in
      hemopoietic stem cell (HSC) transplantation were surveyed. Cyclosporine (CSA)- or
      tacrolimus (FK506)-based regimens were used as graft-vs-host disease (GVHD)
      prophylaxis in allogeneic HSC transplantation. CSF pleocytosis with or without
      neurologic symptoms was detected in 12 of 25 patients receiving allogeneic HSC
      transplants but in none of 11 patients receiving autologous HSC transplants. Of
      the 12 patients with CSF pleocytosis, only one patient developed
      leukoencephalopathy later. There was a correlation between CSF cell numbers and
      trough levels of CSA but not with those of FK506. In patients receiving
      allogeneic HSC transplants, CSF pleocytosis may be relatively common and may
      reflect neurologic damage associated with calcineurin inhibitors.

PMID- 16966275
TI  - Efficacy of intravenous ciprofloxacin in patients with febrile neutropenia
      refractory to initial therapy.
AB  - We previously reported that monotherapy with carbapenem or cefepime exhibited
      efficacy equivalent to cefepime plus an aminoglycoside as initial therapy for
      febrile neutropenia (FN), achieving an adequate response in two-thirds of the
      patients. However, only one-third of the remaining poor responders to monotherapy
      became afebrile after an aminoglycoside was added to the initial carbapenem or
      cefepime. The present study was designed to evaluate the benefit of intravenous
      ciprofloxacin for neutropenic patients with fever who were refractory to initial
      therapy given for the first 3 days. Patients with FN--as defined by an axillary
      temperature >or=37.5 degrees C and a neutrophil count <1,000/microL-who had no
      response to initial therapy with carbapenem or cefepime for 72 hours were to
      receive additional ciprofloxacin 600 mg/day. They were otherwise managed
      according to the Japanese guidelines for FN. An adequate response was defined as
      a decline of temperature to <37.5 degrees C within 7 days after initiation of
      ciprofloxacin treatment. Thirty-one patients with FN (seventeen male and fourteen
      female; mean age 53.1 +/- 14.8 years) were entered in the study. The initial
      antibiotics were cefepime (2 - 4 g/day) in twenty and carbapenem (1 - 2 g/day) in
      eleven. Three patients were excluded from analysis, leaving 28 patients for
      evaluation of efficacy. The response rate was 16/31 patients (51.6%),with four
      patients judged non-assessable due to adverse effects, protocol violation or
      early change to other agents. Adverse events occurred in seventeen patients, but
      all were mild and reversible. Only three patients had adverse events (skin rash,
      hepatic dysfunction and elevation of alkaline phosphatase in one patient,
      respectively) considered related to ciprofloxacin. These findings indicate that
      addition of intravenous ciprofloxacin is effective against FN refractory to
      initial antibiotic therapy and has acceptable toxicity.

PMID- 16966276
TI  - Genotyping of thiopurine methyltransferase in patients with acute leukemia using
      LightCycler PCR.
AB  - Patients with acute lymphoblastic leukemia (ALL) are treated with thiopurines.
      Thiopurine methyltransferase (TPMT) catalyses the S-methylation of thiopurines
      and is subject to genetic polymorphism. The TPMT genotype was determined in 55
      patients with ALL. Three patients were heterozygous for allelic variants of TPMT.
      We describe an assay for the genotyping of the TPMT polymorphism using real-time
      fluorescence polymerase chain reaction (PCR) to facilitate rapid processing of
      samples. This strategy is superior to standard PCR-restriction fragment length
      polymorphism genotyping methods and provides informative data on TPMT
      polymorphisms in patients prior to treatment with thiopurines.

PMID- 16966277
TI  - Down-regulation of wt1 expression in leukemia cell lines as part of apoptotic
      effect in arsenic treatment using two compounds.
AB  - Arsenic trioxide (As2O3) induces remission in patients with acute promyelocytic
      leukemia (APL). To better understand molecular mechanisms of arsenic actions,
      this study investigated the effect of two different arsenic compounds on gene
      expression of apoptosis and cellular proliferation related genes. The Wilms'
      tumor gene (wt1) is up-regulated in acute myeloid leukemia (AML) and a variety of
      leukemia cell lines. The expression of wt1 in these cells is proposed to have an
      anti-apoptotic effect. HL-60 and K562 were treated with arsenic trioxide (As2O3)
      and sodium arsenite (NaAsO2) at concentrations between 0 - 10 microM for up to 48
      h. The induction of apoptosis was accompanied by down-regulation of hTERT and wt1
      mRNA and protein expression but up-regulation of par-4. Low concentrations of 0.1
      microM arsenic induced expression of the anti-apoptotic bcl-2 gene in both cell
      lines HL-60 and K562. There were no major differences encountered between
      compounds. After arsenic treatment of the leukemia cell lines HL-60 and K562 the
      up-regulation of par-4 may contribute to the induction of apoptosis rather than
      down-regulation of bcl-2. The therapeutic effect of arsenic is the induction of
      apoptosis by modulating the gene expression profile of pro- and anti-apoptotic
      genes including the wt1 gene.

PMID- 16966279
TI  - Distinct biological impact of dephosphorylation vs. downregulation of p210Bcr
      Abl: implications for imatinib mesylate response and resistance.
AB  - Imatinib mesylate suppresses phosphorylation of its kinase target, Bcr-Abl. We
      hypothesized that loss of p210Bcr-Abl (the kinase target) may lead to imatinib
      mesylate resistance. We studied K562 cells [chronic myelogenous leukemia (CML)
      blast crisis line] and MO7E/MBA-1 cells (with MBA-1 cells representing MO7E cells
      stably transfected with BCR-ABL). Imatinib mesylate resistance developed when
      p210Bcr-Abl expression was abolished. Furthermore, K562 cells were significantly
      more growth suppressed after imatinib mesylate exposure than after downregulation
      of Bcr-Abl expression. Signaling pathways which were functional in the absence of
      Bcr-Abl expression (NF-kappaB and mitogen-activated protein kinase activation or
      the growth factor pathway) were disrupted when p210Bcr-Abl was present but
      dephosphorylated, suggesting that an intact, but enzymatically inactive Bcr-Abl,
      may interfere with critical growth/signaling pathways. Downregulation of p210Bcr
      Abl may be a mechanism by which imatinib mesylate resistance emerges. Samples
      from three of 15 patients with imatinib mesylate-resistant CML blast crisis had
      undetectable levels of p210Bcr-Abl. We conclude that retention of a
      dephosphorylated p210Bcr-Abl has a biologic impact distinct from that of
      downregulation/loss of p210Bcr-Abl and, in a subset of patients, loss of the
      target of the kinase inhibitor may lead to imatinib mesylate resistance.

PMID- 16966278
TI  - In situ detection of hTERT variants in anaplastic large cell lymphoma.
AB  - The expression of hTERT and its isoforms is difficult to assess in lymphoma
      tissues with the commonly used reverse transcription-polymerase chain reaction
      (RT-PCR) methods, because non-neoplastic lymphocytes expressing hTERT are always
      present in the lymphomatous infiltrates. The present study aimed to investigate
      hTERT mRNA variants in anaplastic large cell lymphoma (ALCL) (n = 38) with in
      situ hybridization (ISH), along with the immunodetection of hTERT protein. Probes
      for the identification of mRNAs containing (Bplus) and lacking (Bdel) exons 7 and
      8 of the hTERT mRNA were used. Normal lymphocyte populations equally expressed
      both Bplus and Bdel mRNAs. Although all ALCL examined were found positive for
      hTERT expression with RT-PCR, hTERT mRNAs were identified in 68% of these tumors
      with ISH, with a higher incidence in the group bearing ALK translocations (10 out
      of 11; 90.9%) compared to the ALK negative group (17 out of 27; 59.3%)
      (PPearson's = 0.002). The same results were obtained with immunohistochemistry
      for hTERT. In approximately 50% of cases, only Bplus positive cells were
      identified, again with a higher incidence in the ALK positive compared to the ALK
      negative group (PPearson's = 0.016). In conclusion, ISH for hTERT mRNAs appears
      to be a valuable tool for the investigation of hTERT expression in lymphomas.
      Aberrations in hTERT variant profiles and a decline in the expression of the B
      deleted isoform may be associated with the pathogenesis of ALCL, especially with
      respect to ALK positive tumors.

PMID- 16966280
TI  - Case 30: hypereosinophilia.
AB  - A young man presented with systemic symptoms and marked eosinophilia.
      Subsequently cyclical weight gain and edema contributed to a diagnosis.

PMID- 16966281
TI  - High activity of rituximab combined with cladribine and cyclophosphamide in a
      patient with pulmonary lymphomatoid granulomatosis and bone marrow involvement.

PMID- 16966282
TI  - Bortezomib is effective in primary plasma cell leukemia.

PMID- 16966283
TI  - Autoimmune marrow fibrosis with cytopenias responsive to methotrexate.

PMID- 16966284
TI  - Non-secretory multiple myeloma with involvement of the hand as initial
      manifestation.

PMID- 16966285
TI  - Primary choroid plexus T-cell lymphoma and multiple aneurysms in the CNS.

PMID- 16966286
TI  - Extensive organizing pneumonia during chemo-immunotherapy containing rituximab
      and G-CSF in a patient with diffuse large B-cell lymphoma: case report and review
      of the literature.

PMID- 16966287
TI  - High efficacy of the CHOP + rituximab association in a case of primary rectal non
      Hodgkin lymphoma (NHL).

PMID- 16966288
TI  - Intravascular large B-cell lymphoma with multisystem involvement.

PMID- 16966289
TI  - Successful treatment of HTLV-1-associated acute adult T-cell leukemia lymphoma by
      allogeneic bone marrow transplantation: a 12 year follow-up.

PMID- 16966290
TI  - Fulminant, but reversible interstitial pneumonitis associated with imatinib
      mesylate.

PMID- 16966291
TI  - Panniculitis-like T-cell lymphoma with an unusual clinical presentation.

PMID- 16966292
TI  - Antimitochondrial antibodies and non-Hodgkin lymphoma presenting as hepatobiliary
      disease.

PMID- 16966293
TI  - Listeria monocytogenes meningitis in two allogeneic hematopoietic stem cell
      transplant recipients.

PMID- 16966294
TI  - Involvement of the appendix and palate by pleomorphic variant mantle cell
      lymphoma.

PMID- 16966295
TI  - A case of erythrodermic-CTCL.

PMID- 16966296
TI  - Small cell variant of T-cell prolymphocytic leukemia exhibiting suppressor
      phenotype.

PMID- 16966297
TI  - Parotitis associated with a parainfluenza virus type 3 infection during aplasia
      after unrelated allogeneic stem cell transplantation.

PMID- 16966298
TI  - Isolated intraperitoneal relapse of AML after allogeneic hematopoietic stem cell
      transplantation in a patient with extensive chronic GVHD and full donor chimerism
      in bone marrow.

PMID- 16966300
TI  - Association between air pollution and multiple respiratory hospitalizations among
      the elderly in Vancouver, Canada.
AB  - Recurrent events, such as repeated hospital admissions for the same health
      outcome, occur frequently in environmental health studies. In this study, we
      conducted an analysis of data on repeated respiratory hospitalizations among the
      elderly in Vancouver, Canada, for the period of June 1, 1995, to March 31, 1999,
      using a new method proposed by (Dewanji and Moolgavkar 2000, 2002) for recurrent
      events, and compared it with some traditional methods. In particular, we assessed
      the impact of ambient gaseous (SO2, NO2, CO, and O3) and particulate pollutants
      (PM10, PM2.5, and PM10-2.5) as well as the coefficient of haze (CoH) on recurrent
      respiratory hospital admissions. Using the new procedure, significant
      associations were found between admissions and 3-day, 5-day, and 7-day moving
      averages of the ambient SO2 concentrations, with the strongest association
      observed at the 7-day lag (RR = 1.044, 95% CI: 1.018-1.070). We also found PM10
      2.5 for 3-day and 5-day lag to be significant, with the strongest association at
      5-day lag (RR = 1.020, 95% CI: 1.001-1.039). No significant associations with
      admission were found with current day exposure.

PMID- 16966301
TI  - Quantitative risk analysis of particulate matter in the air: interspecies
      extrapolation with bioassay and mathematical models.
AB  - We analyzed the health risk of particulate matters in the air to humans using
      bioassay data and a mathematical model. We designed an original dosimetry model
      to estimate the particle concentration in human respiratory organs, and the
      concentration of the inhaled particles at the target organ was used for
      interspecies extrapolation from rat to human. Our model is based on the
      conventional dosimetry model and deposition model in the previous literature, but
      clearance parameters have been newly introduced for the simulation of long-term
      exposure. Lung cancer was set as the risk endpoint in our risk study, and the
      dose-response relationship at the target organ (lung) was quantitatively analyzed
      by the benchmark dose (BMD) method. For interspecies extrapolation based on
      target organ concentration, we assumed benchmark concentration (BMC) related to
      1% excess cancer in rats and humans, and the human equivalent concentration (HEC)
      was searched by back-estimation using our model. The obtained HEC was 948 to 1098
      mg/m3, and the unit risk to humans was 9.11 to 10.5 x 10(-9) per 1 microg/m3 of
      particulate matter. The estimated cancer risk for Japanese people in general was
      estimated as approximately 9-10 persons per 100,000,000 when the particle
      concentration in the air is 10 microg/m3.

PMID- 16966302
TI  - Outdoor air pollution and female lung cancer in Taiwan.
AB  - To investigate the relationship between air pollution and female lung cancer, the
      authors conducted a matched case-control study using female deaths that occurred
      in Taiwan from 1994 through 2003. Data on all eligible female lung cancer deaths
      were obtained from the Bureau of Vital Statistics of the Taiwan Provincial
      Department of Health. The control group consisted of women who died from causes
      other than cancer or diseases associated with respiratory problems. The controls
      were pair matched to the cases by sex, year of birth, and year of death. Each
      matched control was selected randomly from the set of possible controls for each
      case. A municipality-based aggregate index of long-term exposure to air pollution
      was created by dividing the annual average of the measured values for each
      pollutant by the National Ambient Air Quality Standard for that pollutant. The
      ratios for each pollutant were scaled to a 100-point scale and then averaged
      together to generate an index value representing the net burden of these
      pollutants, with each weighted equally. The subjects were divided into tertiles
      according to the levels of the index just described. Women who lived in the group
      of municipalities with highest levels of air pollution exposure index were at a
      statistically significant increased lung cancer risk compared to the group living
      in municipalities with the lowest air pollution exposure index after controlling
      for possible confounders (OR = 1.28, 95% CI = 1.02-1.61). The findings of this
      study warrant further investigation of the role of air pollutants in the etiology
      of lung cancer.

PMID- 16966303
TI  - Aspergillus fumigatus challenge increases cytokine levels in nasal lavage fluid.
AB  - Several studies have shown an association between exposure in moisture-damaged
      buildings and adverse health effects. There are several indicator microbes of
      moisture damage, but Aspergillus fumigatus is one of the best-documented molds
      provoking health problems in different occupational conditions. We assessed
      whether inhalation of a commercial A. fumigatus solution would affect cytokine
      levels (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, IL-4, IL-6,
      interferon [IFN]-gamma) in nasal lavage fluid (NAL) compared with that evoked by
      placebo challenge. Twenty-seven subjects were studied: 13 had occupational
      exposure in a moisture-damaged building, 4 were atopic, and 10 were considered as
      controls. In all the subjects, the IL-1beta levels were increased significantly
      both at 6 (p = 0.013) and 24 h (p = .005) after the A. fumigatus challenge
      compared to placebo. In subjects with previous occupational exposure in a
      moisture-damaged building, IL-4 concentrations were increased significantly both
      at 6 (p =.046) and 24 h (p =.008) after the A. fumigatus challenge compared with
      placebo. Furthermore, in the control group, TNF-alpha levels were significantly
      increased at 6 h after the A. fumigatus challenge compared to placebo (p = .028).
      Thus, these data show a link between markers of inflammation in NAL and
      experimental A. fumigatus challenge.

PMID- 16966304
TI  - Carcinoembryonic antigen, alpha-fetoprotein, and prostate-specific antigen in the
      sera of industrial workers exposed to phenol, formaldehyde, urea, and mixed
      vapors.
AB  - Exposure to certain industrial agents has been thought to have carcinogenic
      potential, both for employees who work closely with agents and for the general
      population that comes into contact with them. The objective of the present study
      is to evaluate the changes at the cellular level or at the level of cellular
      metabolism products present in the biological fluid, and to detect early stages
      of the carcinogenic process resulting from the exposure of industrial
      environmental hazards. Carcinoembryonic antigen (CEA), alpha-fetoproteins (AFP),
      and prostate-specific antigen (PSA) were measured in sera of workers (n = 51),
      who were divided into 4 groups: group I, workers exposed to phenol; group II,
      workers exposed to formaldehyde; group III, workers exposed to urea; and group
      IV, workers exposed to mixed vapor, plus a reference control healthy group (n =
      15). The results showed that 75% of the workers exposed to phenol, 75% of the
      workers exposed to urea, 83.3% of workers exposed to formalin, and 92.3% of the
      workers exposed to mixed vapors had raised values of serum CEA (S-CEA) above
      normal value of the control group. Also, 23% of workers exposed to mixed vapors,
      44% of workers exposed to formalin, 50% of workers exposed to phenol, and 62.5%
      of workers exposed to urea had raised values of serum AFP (S-AFP) above normal
      value of control group. Finally, 16.6% of workers exposed to phenol, 23% of
      workers exposed to mixed vapors, and 33.3% of workers exposed to formalin had
      raised values of serum PSA (S-PSA) above the normal value of control group; there
      were no raised values of S-PSA in workers exposed to urea. No significant
      difference was found in the activities of AST and ALT in group I, but a highly
      significant increase was found in the AST activities for groups II and IV and the
      ALT activities for groups III and IV. A significant difference was found in the
      activity of ALT in group II and in AST for group III. There was no significant
      difference in the levels of albumin in groups I, II, and III, whereas albumin
      levels were significantly decreased in group IV. No significant change was found
      in the level of urea and creatinine in all groups except for group III, where
      serum levels of creatinine were significantly decreased. From our findings, we
      concluded that S-CEA can be used as an important prognostic screening marker for
      early prediction for malignancy, and for management of workers with lung cancer
      who are exposed to the environmental hazards in industrial factories.
      Furthermore, S-AFP can be used also as a biomarker if it is carried out and
      correlated with S-CEA.

PMID- 16966305
TI  - Hyperbaric oxygenation in the treatment of life-threatening isobutyl nitrite
      induced methemoglobinemia--a case report.
AB  - Methemoglobinemia usually results from exposure to oxidizing substances such as
      nitrates or nitrites. Iron within hemoglobin is oxidized from the ferrous (Fe2+)
      state to the ferric (Fe3+) state, resulting in the inability to transport oxygen
      and carbon dioxide. Clinically, this condition causes functional cyanosis. As
      methemoglobin levels increase, patients show evidence of cellular hypoxia in all
      tissues. Death usually occurs when methemoglobin fractions approach 70% of total
      hemoglobin. We describe the case of a 35-year-old female patient with severe life
      threatening isobutyl nitrite-induced methemoglobinemia of 75% of total
      hemoglobin. Toluidine-blue was administered as first-line antidotal therapy
      immediately, followed by hyperbaric oxygenation. The patient recovered
      uneventfully and could be discharged 3 days later.

PMID- 16966306
TI  - Psychosocial severity, length of stay and the role of social work services.
AB  - Data on excess length of stay (LOS)-the difference between actual LOS and target
      LOS for the medical problem-were analyzed for three acute care hospitals. For a
      sample of 2,642 cases, 29.2% of all hospital days were excess days for patients
      referred to social services. For a sample of 176 social service cases, a stepwise
      regression yielded two statistically significant predictors of LOS: (1) Medical
      problem (target LOS) and (2) severity of psychosocial problem (Person-in-
      Environment scale). The importance of psychosocial severity as a predictor of LOS
      has clear implications for the role social workers can play in making health care
      organizations more efficient.

PMID- 16966307
TI  - Social support and health outcomes in a multicultural urban population.
AB  - Data from the Ontario Health Survey were used to examine the relationship between
      levels of social support and general health, suicidal ideation, family
      functioning, and utilization of health services among Metropolitan Toronto
      cultural populations 16-59 years of age (N = 2684). The results of this study
      provided some support for the hypothesis that social support variables correlate
      with general health status. Results also show that being a visible minority
      immigrant is not a risk factor for any of the health outcomes considered here.
      This finding is not in accordance with the notion of social hardship, which
      visible minority immigrants purportedly experience in a predominantly white
      society. Overall, indicators of social support show stronger association with
      mental health outcomes than with physical health ones.

PMID- 16966308
TI  - A qualitative study of hardiness and social support among underserved, inner-city
      minority adults recovering from oral surgery.
AB  - Using qualitative data, this study examines hardiness and social support among
      twenty-two African American and Hispanic subjects, at least 18 years of age, who
      received treatment for a jaw fracture and participated in an hour-long focus
      group to discuss the treatment they received at King/Drew Medical Center, an
      inner-city hospital in Los Angeles, California. Treatment was either a non
      surgical wiring of the teeth closed for six to eight weeks or surgical placement
      of a metal bone plate in the lower jaw with a short period of jaw fixation
      following surgery. A mandibular fracture is one of the most common orofacial
      traumas for minority individuals, and the majority of these fractures among
      patients at urban trauma centers are a result of interpersonal violence. Thus the
      link between psychosocial stress and oral health is evident, yet exposure to
      daily stress does not automatically place one at risk for distress. Some people
      under daily stress have hardiness, conceptualized as an internal personal
      resource consisting of control, commitment, and challenge. This study examines
      hardiness and social support relevant to an underserved, minority population.
      Hardiness and social support were identified and noted in order of frequency
      according to participant characteristics of treatment type, gender, and
      ethnicity. Main themes related to hardiness and social support are highlighted
      with verbatim quotes providing additional context to the theme presented.

PMID- 16966309
TI  - Social well-being of siblings living with a child with diabetes:a qualitative
      study.
AB  - Qualitative data were collected to determine the impact on children where the
      sibling have diabetes. This study represents an attempt to achieve a broad
      perspective and understanding of effects on the well child and family relations.
      In-depth interviews were conducted with siblings and their parents exploring the
      impact of diabetes on sibling's daily lives, sibling relationships and knowledge
      of diabetes. In this study we gained first hand knowledge of the actions and
      reactions of children to their siblings in the context of their daily lives. A
      semi-structured interview guide was used to assist data collection. A sample of
      32 participants was interviewed involving well children and their parents.

PMID- 16966310
TI  - Building community-based short-term psychosocial counseling capacity for cancer
      patients and their families: the Individual Cancer Assistance Network (ICAN)
      model.
AB  - Research studies show that 30% of cancer patients experience significant disease
      related psychosocial distress, which is often under-recognized and undertreated.
      To satisfy the need for increased capacity to deliver accessible, affordable,
      community-based psychosocial counseling for cancer patients and their families,
      the Bristol-Myers Squibb Foundation developed the Individual Cancer Assistance
      Network (ICAN) demonstration project. Results of a 3-phase evaluation in diverse
      community settings in Florida show that ICAN effectively provided "cancer
      sensitivity"; training for social workers preparing them to deliver short-term
      individualized psychosocial counseling, on a sliding fee scale, to cancer
      patients and their families, and to market it effectively to oncologists and the
      community.

PMID- 16966311
TI  - Iraqi Gulf War veteran refugees in the U.S.: PTSD and physical symptoms.
AB  - Veterans of the Gulf War present various symptoms and maladies. Reports by
      governmental and private entities have yielded mixed results and have been
      fraught with criticisms of biased research design. The vast majority of these
      studies have focused on U.S. veterans, with a much smaller number focusing upon
      British veterans. Very few have examined Iraqi Gulf War veterans. Our study
      involves administering a health issues questionnaire to a sample of Iraqi Gulf
      War veteran refugees in the U.S. Results indicate relationships between Post
      Traumatic Stress Disorder (PTSD) scores and health outcome measures of chronic
      fatigue, fibromyalgia, functional status, quality of life, and health care
      utilization in terms of frequency and level of intensity. Implications for
      further inquiry are presented.

PMID- 16966313
TI  - Intra-rater and inter-rater reliability of the 10-point Manual Muscle Test (MMT)
      of strength in children with juvenile idiopathic inflammatory myopathies (JIIM).
AB  - OBJECTIVE: Children with juvenile idiopathic inflammatory myopathies (JIIM)
      present with muscle inflammation and decreased strength that may affect their
      functional abilities. The purpose of this study was to determine the intra-rater
      and inter-rater reliability of the 0 to 10-point manual muscle testing method for
      children with JIIM. METHODS: For the intra-rater and inter-rater reliability
      studies, 10 and 9 children with JIIM participated, respectively. For intra-rater
      reliability, one pediatric therapist completed two assessments in one day with a
      one-hour break. For inter-rater reliability, four therapists assessed the same
      child within a single morning. RESULTS: Spearman correlations for intra-rater
      reliability ranged from 0.70 to 1.00. Kendall's W coefficient for inter-rater
      reliability of groups of muscles (total, proximal, distal, and peripheral) ranged
      from 0.51 to 0.76. CONCLUSIONS: The total, proximal, and peripheral Manual Muscle
      Test (MMT) score, using the 0-10 point scale, has acceptable reliability in JIIM
      patients.

PMID- 16966314
TI  - Searching for evidence in pediatric occupational therapy using free versus
      subscription databases: a comparison of outcomes.
AB  - OBJECTIVE: This study compared the results of searching free versus subscription
      databases and using brief versus comprehensive search strategies to locate
      evidence for three pediatric occupational therapy clinical questions. METHOD:
      Three clinical questions were nominated by practicing pediatric occupational
      therapists. Brief and comprehensive search strategies were then developed.
      Searches were conducted in three free-to-access databases and four subscription
      databases. RESULTS: Based on descriptive data, more relevant citations were
      retrieved using the subscription databases compared with the free databases and
      when using a comprehensive search strategy. Citations that were present in some
      databases were not always retrieved by the searches. This was mainly due to the
      inclusion of an insufficient number of search terms in the brief search
      strategies used in this study and a mismatch between terms used in the search
      strategies and the databases. CONCLUSION: Clinicians may need to use both
      subscription and free databases and use comprehensive search strategies to
      maximize retrieval of relevant articles to answer pediatric clinical questions.

PMID- 16966315
TI  - The effect of positioning for children with cerebral palsy on upper-extremity
      function: a review of the evidence.
AB  - CONTEXT: Controversy exists about the most appropriate seating position for
      children with cerebral palsy (CP) to promote energy conservation and maximize
      upper-extremity function. EVIDENCE ACQUISITION: Sixteen journal articles
      published after 1980 were identified by searching allied health, medical, and
      occupational and physical therapy data bases and evidence-based medicine reviews
      using specific key terms (positioning, wheelchair, postural control, posture,
      adaptive seating devices, patient positioning, cerebral palsy, movement
      disorders, upper extremity, reaching, grasping, and occupational therapy) and
      reviewing bibliographies of retrieved articles. EVIDENCE SYNTHESIS: The majority
      of the evidence supports the positive effects of a neutral to slightly forward
      orientation (whole chair tilted) on upper-extremity function. Only one study did
      not demonstrate such effects. Of the supporting studies, one suggested the
      addition of an abduction orthrosis (AO), one recommended the entire functional
      sitting position (FSP) package (this orientation plus a hip-belt, footrests, AO,
      and cutout tray), and one established the long-term effects of the FSP. One less
      rigorous study opposed the addition of an AO. With the exception of one study,
      most of the evidence states that seat angle does not affect functional abilities.
      However, some of these studies contain faulty methodology and/or their results
      demonstrate clinical significance. CONCLUSION: Evidence supports that children
      with CP should be fitted for wheelchairs that place them in a FSP, which
      includes; orientation in space of 0 degrees -15 degrees, a hip-belt, an AO,
      footrests, and a cutout tray, with the addition of a sloped forward seat of 0
      degrees -15 degrees, to improve upper-extremity function. The exact seat angle
      and orientation in space within the 0 degrees -15 degrees range should be
      determined on an individual basis.

PMID- 16966316
TI  - Sleep issues in children with physical disabilities and their families.
AB  - Sleep has a significant impact on the daily functioning of children and their
      parents. The purpose of this study was to describe the sleep patterns, issues,
      and strategies used to facilitate sleep in children with and without physical
      disabilities and their families. Data were collected from questionnaires
      completed by caregivers and siblings. Caregivers of children with physical
      disabilities reported significantly greater concerns regarding general sleep
      problems, safety, and discomfort at night, night wakening, daytime irritability,
      interference with daytime activities and sleep-related health concerns in
      children with physical disabilities than in their counterparts. Caregivers, but
      not siblings, in families of children with physical disabilities experienced an
      increased prevalence of sleep issues. The most frequently cited strategies to
      alleviate problems were the establishment of consistent routines and provision of
      calming, supportive sleep environments. Pediatric therapists need to assess and
      address sleep issues to promote the well-being of children and their families.

PMID- 16966317
TI  - Exploring occupational therapy and transitions for young children with special
      needs.
AB  - Young children with special needs typically experience many transitions between
      services. As part of a larger family system, each of these transitions and the
      myriad of factors involved affect the life of the child and the lives of their
      families. Occupational therapists have a unique, yet insufficiently explored,
      perspective that may contribute to the support and planning for families and
      children during the transition process. The purpose of this paper is to explore
      the Ecology of Human Performance (EHP) framework (Dunn, Brown & McGuigan, 1994)
      and apply it to occupational therapy and early childhood transitions. A
      description of the transition process and potential occupational therapy
      interventions using the EHP framework is developed.

PMID- 16966318
TI  - School-based occupational therapy for children with fine motor difficulties:
      evaluating functional outcomes and fidelity of services.
AB  - Consultative occupational therapy services are becoming widely used in the school
      environment. However, few studies have evaluated the utility of and the process
      by which these services are delivered. This study examined whether the written
      communication and fine motor skills of 23 children with fine motor difficulties
      improved after receiving school-based occupational therapy from a program whose
      mandate was to deliver services according to a consultation model of service
      delivery. In addition, the study assessed the process of service delivery,
      including treatment fidelity, or the extent to which consultation services were
      implemented as intended. Statistically significant and practically meaningful
      improvement was found in written communication on the Vineland Adaptive Behavior
      Scales-Classroom Edition (VABS-C) and School Functional Assessment-Version 3.0
      (SFA), and in fine motor skills on the SFA, but not on the VABS-C. An examination
      of the service delivery process revealed that therapists deviated from a purely
      consultative model, with 86% providing some direct therapy to children. Parents
      were mostly satisfied with services received, whereas teachers were indifferent
      or somewhat dissatisfied. Treatment fidelity is taken into consideration when
      discussing study findings. Recommendations to enhance school-based occupational
      therapy services delivered according to a primarily consultative model, and
      suggestions for future research, are provided.

PMID- 16966319
TI  - Medium-chain fatty acids as ligands for orphan G protein-coupled receptor GPR84.
AB  - Free fatty acids (FFAs) play important physiological roles in many tissues as an
      energy source and as signaling molecules in various cellular processes. Elevated
      levels of circulating FFAs are associated with obesity, dyslipidemia, and
      diabetes. Here we show that GPR84, a previously orphan G protein-coupled
      receptor, functions as a receptor for medium-chain FFAs with carbon chain lengths
      of 9-14. Medium-chain FFAs elicit calcium mobilization, inhibit 3',5'-cyclic AMP
      production, and stimulate [35S]guanosine 5'-O-(3-thiotriphosphate) binding in a
      GPR84-dependent manner. The activation of GPR84 by medium-chain FFAs couples
      primarily to a pertussis toxin-sensitive G(i/o) pathway. In addition, we show
      that GPR84 is selectively expressed in leukocytes and markedly induced in
      monocytes/macrophages upon activation by lipopolysaccharide. Furthermore, we
      demonstrate that medium-chain FFAs amplify lipopolysaccharide-stimulated
      production of the proinflammatory cytokine interleukin-12 p40 through GPR84. Our
      results indicate a role for GPR84 in directly linking fatty acid metabolism to
      immunological regulation.

PMID- 16966320
TI  - Regulatory factor interactions and somatic silencing of the germ cell-specific
      ALF gene.
AB  - Germ cell-specific genes are active in oocytes and spermatocytes but are silent
      in all other cell types. To understand the basis for this seemingly simple
      pattern of regulation, we characterized factors that recognize the promoter
      proximal region of the germ cell-specific TFIIA alpha/beta-like factor (ALF)
      gene. Two of the protein-DNA complexes formed with liver extracts (C4 and C5) are
      due to the zinc finger proteins Sp1 and Sp3, respectively, whereas another
      complex (C6) is due to the transcription factor RFX1. Two additional complexes
      (C1 and C3) are due to the multivalent zinc finger protein CTCF, a factor that
      plays a role in gene silencing and chromatin insulation. An investigation of CTCF
      binding revealed a recognition site of only 17 bp that overlaps with the Sp1/Sp3
      site. This site is predictive of other genomic CTCF sites and can be aligned to
      create a functional consensus. Studies on the activity of the ALF promoter in
      somatic 293 cells revealed mutations that result in increased reporter activity.
      In addition, RNAi-mediated down-regulation of CTCF is associated with activation
      of the endogenous ALF gene, and both CTCF and Sp3 repress the promoter in
      transient transfection assays. Overall, the results suggest a role for several
      factors, including the multivalent zinc finger chromatin insulator protein CTCF,
      in mediating somatic repression of the ALF gene. Release of such repression,
      perhaps in conjunction with other members of the CTCF, RFX, and Sp1 families of
      transcription factors, could be an important aspect of germ cell gene activation.

PMID- 16966321
TI  - Spectroscopic and kinetic studies of the reaction of bromopropanesulfonate with
      methyl-coenzyme M reductase.
AB  - Methyl-coenzyme M reductase (MCR) catalyzes the final step of methanogenesis in
      which coenzyme B and methyl-coenzyme M are converted to methane and the
      heterodisulfide, CoMS-SCoB. MCR also appears to initiate anaerobic methane
      oxidation (reverse methanogenesis). At the active site of MCR is coenzyme F430, a
      nickel tetrapyrrole. This paper describes the reaction of the active MCR(red1)
      state with the potent inhibitor, 3-bromopropanesulfonate (BPS; I50 = 50 nM) by UV
      visible and EPR spectroscopy and by steady-state and rapid kinetics. BPS was
      shown to be an alternative substrate of MCR in an ionic reaction that is coenzyme
      B-independent and leads to debromination of BPS and formation of a distinct state
      ("MCR(PS)") with an EPR signal that was assigned to a Ni(III)-propylsulfonate
      species (Hinderberger, D., Piskorski, R. P., Goenrich, M., Thauer, R. K.,
      Schweiger, A., Harmer, J., and Jaun, B. (2006) Angew. Chem. Int. Ed. Engl. 45,
      3602-3607). A similar EPR signal was generated by reacting MCR(red1) with several
      halogenated sulfonate and carboxylate substrates. In rapid chemical quench
      experiments, the propylsulfonate ligand was identified by NMR spectroscopy and
      high performance liquid chromatography as propanesulfonic acid after protonolysis
      of the MCR(PS) complex. Propanesulfonate formation was also observed in steady
      state reactions in the presence of Ti(III) citrate. Reaction of the alkylnickel
      intermediate with thiols regenerates the active MCR(red1) state and eliminates
      the propylsulfonate group, presumably as the thioether. MCR(PS) is catalytically
      competent in both the generation of propanesulfonate and reformation of
      MCR(red1). These results provide evidence for the intermediacy of an alkylnickel
      species in the final step in anaerobic methane oxidation and in the initial step
      of methanogenesis.

PMID- 16966322
TI  - Regulation of bone morphogenetic protein-4 activity by sequence elements within
      the prodomain.
AB  - Bone morphogenetic protein-4 (BMP-4) is synthesized as a large precursor protein,
      which undergoes proprotein convertase-mediated proteolytic maturation along the
      secretory pathway to release the active ligand. Pro-BMP-4 is initially cleaved at
      a consensus furin motif adjacent to the mature ligand domain (the S1 site), and
      this allows for subsequent cleavage at an upstream motif (the S2 site). This
      sequential cleavage liberates a small, evolutionarily conserved, prodomain
      fragment (the linker peptide) of unknown fate and function. Here we show that the
      linker domain is essential for proper folding, exit from the endoplasmic
      reticulum, and thus cleavage of the BMP-4 precursor when overexpressed in Xenopus
      oocytes and embryos but not in cultured mammalian cells. Mature BMP-4 synthesized
      from a precursor in which the S1 site is non-cleavable, such that the linker
      domain remains covalently attached to the ligand, has little or no activity in
      vivo. Finally, analysis of folding, cleavage, and bioactivity of chimeric
      precursors containing the BMP-7 prodomain and BMP-4 mature domain, or vice versa,
      with or without the BMP-4 linker domain revealed that the linker domain is only
      functional in the context of the BMP-4 prodomain, and that differential cleavage
      around this domain can regulate the activity of a heterologous ligand.

PMID- 16966323
TI  - Cag pathogenicity island-independent up-regulation of matrix metalloproteinases-9
      and -2 secretion and expression in mice by Helicobacter pylori infection.
AB  - Helicobacter pylori cag pathogenicity island (PAI) is a major determinant of
      gastric injury via induction of several matrix metalloproteinases (MMPs). In the
      present study, we examined the influence of the cag PAI on gastric infection and
      MMP-9 production in mice and in cultured cells. A new mouse colonizing Indian H.
      pylori strain (AM1) that lacks the cag PAI was used to study the cag PAI
      importance in inflammation. Groups of C57BL/6 mice were inoculated separately
      with H. pylori strains AM1 and SS1 (cag+), gastric tissues were histologically
      examined, and bacterial colonization was scored by quantitative culture. Mice
      infected with either cag+ or cag- H. pylori strains showed gastric inflammation
      and elevated MMP-3 production. Significant up-regulation of pro-MMP-9 secretion
      and gene expression in H. pylori infected gastric tissues indicate dispensability
      of cag PAI for increased pro-MMP-9 secretion and synthesis in mice. In agreement,
      cell culture studies revealed that both AM1 and SS1 were equipotent in pro-MMP-9
      induction in human gastric epithelial cells. Both strains showed moderate
      increase in MMP-2 activity in vivo and in vitro. In addition, increased secretion
      of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 induced
      pro-MMP-9 secretion and synthesis in AM1 or SS1 strain-infected mice suggesting
      elicitation of pro-inflammatory cytokines by both cag- and cag+ genotype.
      Moreover, tissue inhibitors of metalloproteinase-1 expression were decreased with
      increase in pro-MMP-9 induction. These data show that H. pylori may act through
      different pathways other than cag PAI-mediated for gastric inflammation and
      contribute to up-regulation of MMP-9 via pro-inflammatory cytokines.

PMID- 16966324
TI  - Sumoylated SnoN represses transcription in a promoter-specific manner.
AB  - The transcriptional modulator SnoN controls a diverse set of biological
      processes, including cell proliferation and differentiation. The mechanisms by
      which SnoN regulates these processes remain incompletely understood. Recent
      studies have shown that SnoN exerts positive or negative regulatory effects on
      transcription. Because post-translational modification of proteins by small
      ubiquitin-like modifier (SUMO) represents an important mechanism in the control
      of the activity of transcriptional regulators, we asked if this modification
      regulates SnoN function. Here, we show that SnoN is sumoylated. Our data
      demonstrate that the SUMO-conjugating E2 enzyme Ubc9 is critical for SnoN
      sumoylation and that the SUMO E3 ligase PIAS1 selectively interacts with and
      enhances the sumoylation of SnoN. We identify lysine residues 50 and 383 as the
      SUMO acceptor sites in SnoN. Analyses of SUMO "loss-of-function" and "gain-of
      function" SnoN mutants in transcriptional reporter assays reveal that sumoylation
      of SnoN contributes to the ability of SnoN to repress gene expression in a
      promoter-specific manner. Although this modification has little effect on SnoN
      repression of the plasminogen activator inhibitor-1 promoter and only modestly
      potentiates SnoN repression of the p21 promoter, SnoN sumoylation robustly
      augments the ability of SnoN to suppress transcription of the myogenesis master
      regulatory gene myogenin. In addition, we show that the SnoN SUMO E3 ligase,
      PIAS1, at its endogenous levels, suppresses myogenin transcription. Collectively,
      our findings suggest that SnoN is directly regulated by sumoylation leading to
      the enhancement of the ability of SnoN to repress transcription in a promoter
      specific manner. Our study also points to a physiological role for SnoN
      sumoylation in the control of myogenin expression in differentiating muscle
      cells.

PMID- 16966325
TI  - Loss of Ikkbeta promotes migration and proliferation of mouse embryo fibroblast
      cells.
AB  - The IkappaB kinase complex (IKK) is central to the activation of NF-kappaB, a
      critical transcription factor governing expression of genes involved in cell
      proliferation and anti-apoptotic responses. Mice with genetic disruptions of the
      Ikkbeta or Ikkgamma gene loci die during embryogenesis because of severe hepatic
      apoptosis. We now show that Ikkbeta gene deficiency promotes migration and
      proliferation of mouse embryo fibroblast cells. Morphological analyses revealed
      an unusual protrusion of the cytoplasm in Ikkbeta(-/-) cells when cultured at a
      lower density. In a Boyden chamber assay, Ikkbeta(-/-) cells exhibited a high
      rate of invasion and migration. Enhanced formation of actin stress fibers was
      also observed in the Ikkbeta(-/-) cells. Mechanistic studies indicated that
      IKKbeta affects the expression of proteins involved in the assembly of
      cytoskeleton and cell movement. Furthermore, re-expression of Ikkbeta and
      antioxidant treatment in Ikkbeta(-/-) cells caused a reversal of protrusive
      phenotype and high motility, respectively. Furthermore, elimination of reactive
      oxygen species (ROS) blocked expression of snail and subsequently derepressed E
      cadherin expression. Although the underlying mechanism is likely entangled and
      complicated, the data presented indicate that generation of ROS played a key role
      in the morphological and mobility changes in Ikkbeta(-/-) cells. These data thus
      suggest that IKKbeta provides inhibitory signals for cell mobility and growth.
      Deficiency in the Ikkbeta gene promotes cell mobilization, at least partially,
      through a ROS-dependent mechanism.

PMID- 16966326
TI  - Induction of transcriptionally active Jun proteins regulates drug-induced
      senescence.
AB  - The drug hydroxyurea (HU) is used for cancer therapy and treatment of sickle cell
      anemia. It inhibits cell cycle progression by blocking DNA synthesis and drives
      cells to undergo apoptosis or enter senescence. We demonstrate here that HU
      induces the expression of two AP-1 proteins, c-Jun and JunB, which exert
      antagonistic effects on the cell cycle. Moreover, the induction of c-Jun is
      observed following treatment with two other drugs that inhibit the cell cycle in
      S phase, aphidicolin and camptothecin. The induction of c-Jun, which promotes
      cell cycle progression, up-regulates expression of cyclin D after exposure of
      cells to HU. Deficiency in c-jun prevents elevation of cyclin D expression and
      extends entrance into HU-induced senescence but also renders cells more resistant
      to HU-dependent apoptosis. The induction of c-Jun is independent of JNK activity,
      and additionally, of c-Jun autoregulatory activity but is inhibited upon
      inhibition of protein kinase C activity. Therefore, we suggest that c-Jun
      activity prevents drug-induced senescence. Conversely, the JunB target gene,
      tumor suppressor p16(INK4a), a cyclin-dependent kinase inhibitor essential for
      the induction of drug-induced senescence, is also up-regulated by HU in a JunB
      dependent manner. Constitutive expression of JunB up-regulates p16(INK4a) and
      increases the sensitivity of mouse fibroblasts to drug-induced-senescence. Thus,
      we suggest that in contrast to c-Jun, JunB drives cells to enter HU-dependent
      senescence. The effect of HU treatment, which regulates the intricate web of AP-1
      transcription, depends on the balance between c-Jun and JunB activities.

PMID- 16966327
TI  - A typical N-terminal extensions confer novel regulatory properties on GTP
      cyclohydrolase isoforms in Drosophila melanogaster.
AB  - The cofactor tetrahydrobiopterin plays critical roles in the modulation of the
      signaling molecules dopamine, serotonin, and nitric oxide. Deficits in cofactor
      synthesis have been associated with several human hereditary diseases.
      Responsibility for the regulation of cofactor pools resides with the first enzyme
      in its biosynthetic pathway, GTP cyclohydrolase I. Because organisms must be able
      to rapidly respond to environmental and developmental cues to adjust output of
      these signaling molecules, complex regulatory mechanisms are vital for signal
      modulation. Mammalian GTP cyclohydrolase is subject to end-product inhibition via
      an associated regulatory protein and to positive regulation via phosphorylation,
      although target residues are unknown. GTP cyclohydrolase is composed of a highly
      conserved homodecameric catalytic core and non-conserved N-terminal domains
      proposed to be regulatory sites. We demonstrate for the first time in any
      organism that the N-terminal arms of the protein serve regulatory functions. We
      identify two different modes of regulation of the enzyme mediated through the N
      terminal domains. The first is end-product feedback inhibition, catalytically
      similar to that of the mammalian enzyme, except that feedback inhibition by the
      cofactor requires sequences in the N-terminal arms rather than a separate
      regulatory protein. The second is a novel inhibitory interaction between the N
      terminal arms and the active sites, which can be alleviated through the
      phosphorylation of serine residues within the N termini. Both mechanisms allow
      for acute and highly responsive regulation of cofactor production as required by
      downstream signaling pathways.

PMID- 16966328
TI  - The role of a conserved serine residue within hydrogen bonding distance of FAD in
      redox properties and the modulation of catalysis by Ca2+/calmodulin of
      constitutive nitric-oxide synthases.
AB  - The crystal structure of the neuronal nitric-oxide synthase (nNOS) NADPH/FAD
      binding domain indicated that Ser-1176 is within hydrogen bonding distance of Asp
      1393 and the O4 atom of FAD and is also near the N5 atom of FAD (3.7 A). This
      serine residue is conserved in most of the ferredoxin-NADP+ reductase family of
      proteins and is important in electron transfer. In the present study, the
      homologous serines of both nNOS (Ser-1176) and endothelial nitric-oxide synthase
      (eNOS) (Ser-942) were mutated to threonine and alanine. Both substitutions
      yielded proteins that exhibited decreased rates of electron transfer through the
      flavin domains, in the presence and absence of Ca2+/CaM, as measured by reduction
      of potassium ferricyanide and cytochrome c. Rapid kinetics measurements of flavin
      reduction of all the mutants also showed a decrease in the rate of flavin
      reduction, in the absence and presence of Ca2+/CaM, as compared with the wild
      type proteins. The serine to alanine substitution caused both nNOS and eNOS to
      synthesize NO more slowly; however, the threonine mutants gave equal or slightly
      higher rates of NO production compared with the wild type enzymes. The midpoint
      redox potential measurements of all the redox centers revealed that wild type and
      threonine mutants of both nNOS and eNOS are very similar. However, the redox
      potentials of the FMN/FMNH* couple for alanine substitutions of both nNOS and
      eNOS are >100 mV higher than those of wild type proteins and are positive. These
      data presented here suggest that hydrogen bonding of the hydroxyl group of serine
      or threonine with the isoalloxazine ring of FAD and with the amino acids in its
      immediate milieu, particularly nNOS Asp-1393, affects the redox potentials of
      various flavin states, influencing the rate of electron transfer.

PMID- 16966330
TI  - Phosphorylation of Tyr1214 within VEGFR-2 triggers the recruitment of Nck and
      activation of Fyn leading to SAPK2/p38 activation and endothelial cell migration
      in response to VEGF.
AB  - VEGFR-2 is the major receptor that regulates the different functions of VEGF in
      adults. We have previously reported that following VEGF treatment of endothelial
      cells, VEGFR-2 is phosphorylated on Tyr1214 upstream of the Cdc42-SAPK2/p38
      MAPKAP K2 pathway. However, little is known of the earliest molecular events that
      compose the SAPK2/p38 pathway following VEGFR-2 activation. In this study, we
      address this question using HA-tagged constructs of either wild-type VEGFR-2 or
      Y1214F VEGFR-2 mutant in immunoprecipitation assays. We show that the Src family
      kinase member Fyn, but not c-Src itself, is recruited to VEGFR-2 and is activated
      in a p-Tyr1214-dependent manner. We also report that the SH2 domain-containing
      adapter molecule Nck, but not Grb2, is recruited to VEGFR-2 in a p-Tyr1214
      dependent manner and that it associates with Fyn. Moreover, PAK-2 is
      phosphorylated in a Fyn-dependent manner. Using chemical and genetic inhibitors,
      we show that Fyn activity is required for SAPK2/p38 but not for FAK activation in
      response to VEGF. In contrast, c-Src permits activation of FAK, but not that of
      SAPK2/p38. In addition, Fyn is required for stress fiber formation and
      endothelial cell migration. We propose a model in which Fyn forms a molecular
      complex with Nck and PAK-2 and suggest that this complex assembles in a p-Tyr1214
      dependent manner within VEGFR-2 following VEGF treatment. In turn, this triggers
      the activation of the SAPK2/p38 MAP kinase module, and promotes stress fiber
      formation and endothelial cell migration.

PMID- 16966329
TI  - Regulation of Ncx1 expression. Identification of regulatory elements mediating
      cardiac-specific expression and up-regulation.
AB  - The Na+-Ca2+ exchanger (NCX1) is up-regulated in hypertrophy and is often found
      up-regulated in end-stage heart failure. Studies have shown that the change in
      its expression contributes to contractile dysfunction. We have previously shown
      that the 1831-bp Ncx1 H1 (1831Ncx1) promoter directs cardiac-specific expression
      of the exchanger in both development and in the adult, and is sufficient for the
      up-regulation of Ncx1 in response to pressure overload. Here, we utilized
      adenoviral mediated gene transfer and transgenics to identify minimal regions and
      response elements that mediate Ncx1 expression in the heart. We demonstrate that
      the proximal 184 bp of the Ncx1 H1 (184Ncx1) promoter is sufficient for
      expression of reporter genes in adult cardiomyocytes and for the correct
      spatiotemporal pattern of Ncx1 expression in development but not for up
      regulation in response to pressure overload. Mutational analysis revealed that
      both the -80 CArG and the -50 GATA elements were required for expression in
      isolated adult cardiomyocytes. Chromatin immunoprecipitation assays in adult
      cardiocytes demonstrate that SRF and GATA4 are associated with the proximal
      region of the endogenous Ncx1 promoter. Transgenic lines were established for the
      1831Ncx1 promoter-luciferase containing mutations in the -80 CArG or -50 GATA
      element. No luciferase activity was detected during development, in the adult, or
      after pressure overload in any of the -80 CArG transgenic lines. The Ncx1 -50
      GATA mutant promoter was sufficient for driving the normal spatiotemporal pattern
      of Ncx1 expression in development and for up-regulation in response to pressure
      overload but importantly, expression was no longer cardiac restricted. This work
      is the first in vivo study that demonstrates which cis elements are important for
      Ncx1 regulation.

PMID- 16966331
TI  - Involvement of the conserved adaptor protein Alix in actin cytoskeleton assembly.
AB  - The conserved adaptor protein Alix, also called AIP1 or Hp95, promotes flattening
      and alignment of cultured mammalian fibroblasts; however, the mechanism by which
      Alix regulates fibroblast morphology is not understood. Here we demonstrate that
      Alix in WI38 cells, which require Alix expression for maintaining typical
      fibroblast morphology, associates with filamentous actin (F-actin) and F-actin
      based structures lamellipodia and stress fibers. Reducing Alix expression by
      small interfering RNA (siRNA) decreases F-actin content and inhibits stress fiber
      assembly. In cell-free systems, Alix directly interacts with F-actin at both the
      N-terminal Bro1 domain and the C-terminal proline-rich domain. In Alix
      immunoprecipitates from WI38 cell lysates, actin is the most abundant partner
      protein of Alix. In addition, the N-terminal half of the middle region of Alix
      binds cortactin, an activator of the ARP2/3 complex-mediated initiation of actin
      polymerization. Alix is required for lamellipodial localization of cortactin. The
      C-terminal half of the middle region of Alix interacts with alpha-actinin, a key
      factor that bundles F-actin in stress fibers. Alix knockdown decreases the amount
      of alpha-actinin that associates with F-actin. These findings establish crucial
      involvement of Alix in actin cytoskeleton assembly.

PMID- 16966332
TI  - Group VIA calcium-independent phospholipase A2 mediates endothelial cell S phase
      progression.
AB  - Arachidonic acid and its metabolites have been previously implicated in the
      regulation of endothelial cell proliferation. Arachidonic acid may be liberated
      from cellular phospholipids by the action of group VIA calcium-independent
      phospholipase A2 (iPLA2-VIA). Consequently, we tested the hypothesis that iPLA2
      VIA activity is linked to the regulation of endothelial cell proliferation.
      Inhibition of iPLA2 activity by bromoenol lactone (BEL) was sufficient to
      entirely block endothelial cell growth. BEL dose-dependently inhibited
      endothelial cell DNA synthesis in a manner that was reversed upon the exogenous
      addition of arachidonic acid. DNA synthesis was inhibited by the S-isomer and not
      by the R-isomer of BEL, demonstrating that endothelial cell proliferation is
      mediated specifically by iPLA2-VIA. iPLA2-VIA activity was critical to the
      progression of endothelial cells through S phase and is required for the
      expression of the cyclin A/cdk2 complex. Thus, inhibition of iPLA2-VIA blocks S
      phase progression and results in exit from the cell cycle. Inhibition of iPLA2
      VIA-mediated endothelial cell proliferation is sufficient to block angiogenic
      tubule formation in co-culture assays. Consequently, iPLA2-VIA is a novel
      regulator of endothelial cell S phase progression, cell cycle residence, and
      angiogenesis.

PMID- 16966333
TI  - Structural snapshots of Escherichia coli histidinol phosphate phosphatase along
      the reaction pathway.
AB  - HisB from Escherichia coli is a bifunctional enzyme catalyzing the sixth and
      eighth steps of l-histidine biosynthesis. The N-terminal domain (HisB-N)
      possesses histidinol phosphate phosphatase activity, and its crystal structure
      shows a single domain with fold similarity to the haloacid dehalogenase (HAD)
      enzyme family. HisB-N forms dimers in the crystal and in solution. The structure
      shows the presence of a structural Zn(2+) ion stabilizing the conformation of an
      extended loop. Two metal binding sites were also identified in the active site.
      Their presence was further confirmed by isothermal titration calorimetry. HisB-N
      is active in the presence of Mg(2+), Mn(2+), Co(2+), or Zn(2+), but Ca(2+) has an
      inhibitory effect. We have determined structures of several intermediate states
      corresponding to snapshots along the reaction pathway, including that of the
      phosphoaspartate intermediate. A catalytic mechanism, different from that
      described for other HAD enzymes, is proposed requiring the presence of the second
      metal ion not found in the active sites of previously characterized HAD enzymes,
      to complete the second half-reaction. The proposed mechanism is reminiscent of
      two-Mg(2+) ion catalysis utilized by DNA and RNA polymerases and many nucleases.
      The structure also provides an explanation for the inhibitory effect of Ca(2+).

PMID- 16966334
TI  - Evolution of a basic helix-loop-helix protein from a transcriptional repressor to
      a plastid-resident regulatory factor: involvement in hypersensitive cell death in
      tobacco plants.
AB  - The tobacco gene NtWIN4 (Nicotiana tabacum wound-induced clone 4) is transiently
      up-regulated in response not only to wounding but also to pathogen attack. NtWIN4
      encodes a putative basic helix-loop-helix protein with an apparent molecular mass
      of 28 kDa that exhibited clear nuclear transcription repression activity in Dual
      Luciferase assays. However, immunoblotting indicated the existence of a 17-kDa
      form of NtWIN4 localized exclusively in tobacco leaf chloroplasts. Subsequent
      peptide dissection analyses with green fluorescent protein fusions revealed that
      a polypeptide of 81 amino acids starting at position 13 from the N terminus is
      maximally necessary for this localization. Further fine dissection analysis
      strongly suggested that the protein actually begins at the second Met located at
      position 27, yielding a signal peptide of 67 amino acids. However, the last C
      terminal 15 amino acids overlap with the conserved basic region critical for DNA
      binding, so NtWIN4 presumably does not function as a transcription factor in
      planta. Transgenic tobacco plants constitutively overexpressing NtWIN4
      demonstrated mortality with abnormal features, including albinism, and transient
      expression upon agroinfiltration resulted in distinct necrosis with a sharp
      decrease in chlorophyll content, consistent with the phenomenon known as
      chlorosis. Transgenic RNA interference tobacco plants exhibited reduced
      hypersensitive cell death, showing delayed tissue necrosis upon pathogen
      infection. These results suggest that NtWIN4 arose by divergence, becoming a
      chloroplast-resident factor from a nuclear transcriptional repressor by obtaining
      a transit peptide sequence, and that, upon translocation, it interacts with
      chloroplast components to induce hypersensitive cell death through chloroplast
      disruption, thereby contributing to plant stress responses.

PMID- 16966335
TI  - Functional and biochemical analysis of the N-terminal domain of phytochrome A.
AB  - Phytochrome A (phyA) is a versatile plant photoreceptor that mediates responses
      to brief light exposures (very low fluence responses, VLFR) as well as to
      prolonged irradiation (high irradiance responses, HIR). We identified the phyA
      303 mutant allele of Arabidopsis thaliana bearing an R384K substitution in the
      GAF subdomain of the N-terminal half of phyA. phyA-303 showed reduced phyA
      spectral activity, almost normal VLFR, and severely impaired HIR. Recombinant N
      terminal half oat of PHYA bearing the phyA-303 mutation showed poor incorporation
      of chromophore in vitro, despite the predicted relatively long distance (>13 A)
      between the mutation and the closest ring of the chromophore. Fusion proteins
      bearing the N-terminal domain of oat phyA, beta-glucuronidase, green fluorescent
      protein, and a nuclear localization signal showed physiological activity in
      darkness and mediated VLFR but not HIR. At equal protein levels, the phyA-303
      mutation caused slightly less activity than the fusions containing the wild-type
      sequence. Taken together, these studies highlight the role of the N-terminal
      domain of phyA in signaling and of distant residues of the GAF subdomain in the
      regulation of phytochrome bilin-lyase activity.

PMID- 16966336
TI  - A novel positive feedback loop between peroxisome proliferator-activated receptor
      delta and prostaglandin E2 signaling pathways for human cholangiocarcinoma cell
      growth.
AB  - Peroxisome proliferator-activated receptor-delta (PPARdelta) is a nuclear
      receptor implicated in lipid oxidation and the pathogenesis of obesity and
      diabetes. This study was designed to examine the potential effect of PPARdelta on
      human cholangiocarcinoma cell growth and its mechanism of actions. Overexpression
      of PPARdelta or activation of PPARdelta by its pharmacological ligand, GW501516,
      at low doses (0.5-50 nM) promoted the growth of three human cholangiocarcinoma
      cell lines (CCLP1, HuCCT1, and SG231). This effect was mediated by induction of
      cyclooxygenase-2 (COX-2) gene expression and production of prostaglandin E2
      (PGE2) that in turn transactivated epidermal growth factor receptor (EGFR) and
      Akt. In support of this, inhibition of COX-2, EGFR, and Akt prevented the
      PPARdelta-induced cell growth. Furthermore, PPARdelta activation or PGE2
      treatment induced the phosphorylation of cytosolic phospholipase A2alpha
      (cPLA2alpha), a key enzyme that releases arachidonic acid (AA) substrate for PG
      production via COX. Overexpression or activation of cPLA2alpha enhanced PPARdelta
      binding to PPARdelta response element (DRE) and increased PPARdelta reporter
      activity, indicating a novel role of cPLA2alpha for PPARdelta activation.
      Consistent with this, AA enhanced the binding of PPARdelta to DRE, in vitro,
      suggesting a direct role of AA for PPARdelta activation. In contrast, although
      PGE2 treatment increased the DRE reporter activity in intact cells, it failed to
      induce PPARdelta binding to DRE in cell-free system, suggesting that cPLA2alpha
      mediated AA release is required for PGE2-induced PPARdelta activation. Taken
      together, these observations reveal that PPARdelta induces COX-2 expression in
      human cholangiocarcinoma cells and that the COX-2-derived PGE2 further activates
      PPARdelta through phosphorylation of cPLA2alpha. This positive feedback loop
      plays an important role for cholangiocarcinoma cell growth and may be targeted
      for chemoprevention and treatment.

PMID- 16966337
TI  - PLPD: reliable protein localization prediction from imbalanced and overlapped
      datasets.
AB  - Subcellular localization is one of the key functional characteristics of
      proteins. An automatic and efficient prediction method for the protein
      subcellular localization is highly required owing to the need for large-scale
      genome analysis. From a machine learning point of view, a dataset of protein
      localization has several characteristics: the dataset has too many classes (there
      are more than 10 localizations in a cell), it is a multi-label dataset (a protein
      may occur in several different subcellular locations), and it is too imbalanced
      (the number of proteins in each localization is remarkably different). Even
      though many previous works have been done for the prediction of protein
      subcellular localization, none of them tackles effectively these characteristics
      at the same time. Thus, a new computational method for protein localization is
      eventually needed for more reliable outcomes. To address the issue, we present a
      protein localization predictor based on D-SVDD (PLPD) for the prediction of
      protein localization, which can find the likelihood of a specific localization of
      a protein more easily and more correctly. Moreover, we introduce three
      measurements for the more precise evaluation of a protein localization predictor.
      As the results of various datasets which are made from the experiments of Huh et
      al. (2003), the proposed PLPD method represents a different approach that might
      play a complimentary role to the existing methods, such as Nearest Neighbor
      method and discriminate covariant method. Finally, after finding a good boundary
      for each localization using the 5184 classified proteins as training data, we
      predicted 138 proteins whose subcellular localizations could not be clearly
      observed by the experiments of Huh et al. (2003).

PMID- 16966338
TI  - Site-directed spin labeling measurements of nanometer distances in nucleic acids
      using a sequence-independent nitroxide probe.
AB  - In site-directed spin labeling (SDSL), local structural and dynamic information
      is obtained via electron paramagnetic resonance (EPR) spectroscopy of a stable
      nitroxide radical attached site-specifically to a macromolecule. Analysis of
      electron spin dipolar interactions between pairs of nitroxides yields the inter
      nitroxide distance, which provides quantitative structural information. The
      development of pulse EPR methods has enabled such distance measurements up to 70
      A in bio-molecules, thus opening up the possibility of SDSL global structural
      mapping. This study evaluates SDSL distance measurement using a nitroxide
      (designated as R5) that can be attached, in an efficient and cost-effective
      manner, to a phosphorothioate backbone position at arbitrary DNA or RNA
      sequences. R5 pairs were attached to selected positions of a dodecamer DNA duplex
      with a known NMR structure, and eight distances, ranging from 20 to 40 A, were
      measured using double electron-electron resonance (DEER). The measured distances
      correlated strongly (R2 = 0.98) with the predicted values calculated based on a
      search of sterically allowable R5 conformations in the NMR structure, thus
      demonstrating accurate distance measurements using R5. Furthermore, distance
      measurement in a 42 kD DNA was demonstrated. The results establish R5 as a
      sequence-independent probe for global structural mapping of DNA and DNA-protein
      complexes.

PMID- 16966339
TI  - Maternal depression increases infant risk of diarrhoeal illness: --a cohort
      study.
AB  - AIMS: To examine the associations between postnatal depression in mothers and
      diarrhoeal illness in their infants in the first year of life in a low-income
      country. METHODS: Using a prospective cohort design, 265 infants (n = 130 of
      mothers having a depressive episode according to the International Classification
      of Diseases, 10th revision, at 3 months postnatal and n = 135 of psychologically
      well mothers) living in rural Rawalpindi, Pakistan, were followed up for 1 year.
      Frequency of diarrhoeal episodes was measured fortnightly by health workers using
      a standard questionnaire. RESULTS: Infants of depressed mothers had significantly
      more diarrhoeal episodes per year than those of controls (mean 5.5 v 4.0; 95%
      confidence interval (CI) 0.9 to 2.0). The relative risk of having > or =5
      diarrhoeal episodes per year in infants of depressed mothers was 2.3 (95% CI 1.6
      to 3.1). The association remained significant after adjustment for other risk
      factors by multivariate analysis. CONCLUSIONS: Maternal depression is associated
      with infant diarrhoeal morbidity in a low-income community setting. It is
      independent of the effects of known factors such as undernutrition, socioeconomic
      status and parental education. Preventive child health programmes targeting
      mothers must consider their mental health.

PMID- 16966340
TI  - Assessment of ventricular dyssynchrony: global or regional function?

PMID- 16966341
TI  - A rare case of single giant cardiac hamartomas in an adult patient.

PMID- 16966342
TI  - Myocardial metastasis of a bronchial carcinoid.

PMID- 16966343
TI  - Determinants of microvascular flow.

PMID- 16966344
TI  - Anti-inflammatory effects of angiotensin-converting enzyme inhibitors and
      angiotensin receptor blockers: Potential benefits for the prevention of atrial
      fibrillation.

PMID- 16966345
TI  - Rare coronary anomaly coexisting with atrial septal defect: contraindication to
      Amplatzer occluder implantation.

PMID- 16966346
TI  - Leptin and vascular function: Friend or foe?

PMID- 16966347
TI  - Effects of cardiac resynchronization therapy on overall mortality and mode of
      death: a meta-analysis of randomized controlled trials.
AB  - AIMS: Cardiac resynchronization therapy (CRT) has been shown to improve symptoms
      and exercise tolerance in patients with advanced heart failure (HF). However,
      studies were underpowered to address its effect on overall mortality. To evaluate
      whether CRT alone (without a combined defibrillator function) reduces overall
      mortality as compared with optimal pharmacological therapy, and how it affects
      the mode of death in patients with advanced HF. METHODS AND RESULTS: Public
      domain databases were systematically searched. Randomized controlled studies that
      evaluated the effects of CRT alone in patients with advanced HF and a depressed
      left ventricular systolic performance were selected for this analysis. Trials,
      which did not independently report data on CRT alone or had a follow-up period of
      less than 3 months, were excluded. Five studies were identified and analyzed.
      They included a total of 2371 patients, 1028 controls and 1343 CRT-treated
      patients. Pooled analysis demonstrated that CRT alone, as compared with optimal
      medical therapy, significantly reduced all-cause mortality by 29% [16.9 vs.
      20.7%; odds ratio (OR), 0.71; 95% confidence interval (CI), 0.57-0.88] and
      mortality due to progressive HF by 38% (6.7 vs. 9.7%; OR, 0.62; 95% CI, 0.45
      0.84). No effect on sudden cardiac death (SCD) was observed with CRT (6.4 vs.
      5.9%; OR, 1.04; 95% CI, 0.73-1.22). CONCLUSIONS: CRT alone as compared with
      optimal medical therapy reduces all-cause mortality in patients with advanced HF.
      It predominantly reduces worsening HF mortality, not affecting SCD.

PMID- 16966348
TI  - Ganirelix acetate causes a rapid reduction in estradiol levels without adversely
      affecting oocyte maturation in women pretreated with leuprolide acetate who are
      at risk of ovarian hyperstimulation syndrome.
AB  - BACKGROUND: Elevated estradiol (E(2)) levels predispose to development of ovarian
      hyperstimulation syndrome (OHSS). Since GnRH antagonist is associated with a
      reduction in E(2) levels, we hypothesized that GnRH-antagonist treatment of women
      down-regulated with GnRH agonist who are at risk of OHSS might reduce E(2) levels
      and avoid cycle cancellation. METHODS: Retrospective study in a university-based
      assisted reproduction technology (ART) programme in 87 patients treated with long
      luteal (LL) or microdose flare (MDF) with ovarian hyperresponse and 87 control
      patients without ovarian hyperresponse. GnRH-antagonist (ganirelix acetate)
      treatment was started and leuprolide acetate discontinued in women who failed to
      respond to a reduction in gonadotrophin dosage. RESULTS: In the treatment group,
      there was a significant, reproducible reduction in serum E(2) levels. Mean E(2)
      at the start of ganirelix treatment was 4219.8 pg/ml and decreased in 24 h to
      2613.7 pg/ml (36.7%; P < 0.001). An average of 24.9 +/- 8.8 oocytes were obtained
      at retrieval and an average of 19.1 +/- 8.0 were metaphase II (79.2%).
      Fertilization occurred in 13.9 +/- 8.1 embryos (72.8%). In this high risk group,
      two cases of severe OHSS (2.3%) occurred. The ongoing pregnancy rate was 51.8%.
      Compared with the control group, there were no statistically significant
      differences in the rate of oocyte recovery, oocyte maturity, 2PN rate,
      fertilization, cancellation, OHSS or pregnancy. CONCLUSIONS: GnRH-antagonist
      treatment of women pretreated with GnRH agonist rapidly reduced circulating serum
      E(2) without adversely affecting oocyte maturation, fertilization rates or embryo
      quality and resulted in a high pregnancy rate in this subgroup of patients at
      risk of OHSS.

PMID- 16966349
TI  - Successful delivery after the transfer of twice-vitrified embryos derived from in
      vitro matured oocytes: a case report.
AB  - We report here the first case of successful pregnancy and delivery after the
      blastocyst transfer of twice-vitrified embryos produced following in vitro
      maturation (IVM) and ICSI. The patient received 5000 IU hCG on day 12 of the
      treatment cycle, and oocyte retrieval was carried out 36 h after hCG injection. A
      total of 22 immature oocytes were obtained. Following incubation for 26 h in IVM
      medium, 15 oocytes (68.2%) reached metaphase II stage. In total, 13 oocytes
      (86.7%) were fertilized after ICSI with the husband's sperm, and 11 embryos at
      the pronuclear stage and two cleaved embryos on day 2 were vitrified because of
      thin endometrial thickness. Eight cryopreserved embryos at the pronuclear stage
      were warmed and cultured until the day 3 stage. Three embryos were transferred,
      and three embryos were twice vitrified. Unfortunately, these transferred embryos
      did not implant. Three twice-vitrified embryos were rewarmed and cultured until
      the day 5 stage, and two embryos were transferred. The second transfer attempt of
      twice-vitrified embryos resulted in the full-term delivery of a healthy infant.
      This case report demonstrates that twice-vitrified embryos, developed using an
      IVM protocol, retain the developmental competence for full-term, healthy infants.

PMID- 16966350
TI  - Is smoking a risk factor for decreased semen quality? A cross-sectional analysis.
AB  - BACKGROUND: Previous studies suggest a deleterious effect of cigarette smoking on
      semen quality, but their results have not been consistent. We studied the
      association between current smoking and semen characteristics and hormonal levels
      in a large group of healthy men. METHODS: From 1987 to 2004, seven separate
      occupational or environmental semen quality studies were co-ordinated by our
      department. A total of 2562 men participated, each providing semen and blood
      sample and answering a questionnaire about lifestyle and factors related to
      health. Appropriate semen and smoking data were available for 2542 men. RESULTS:
      Adjusting for study, age and other covariates, we observed an inverse dose
      response relation between smoking and semen volume, total sperm count and
      percentage motile sperm. Heavy smokers had a 19% lower sperm concentration than
      non-smokers. We found a positive dose-response relationship between smoking and
      testosterone, LH and the LH/free testosterone ratios. CONCLUSION: Current smoking
      in adult life moderately impairs the semen quality. It is well known that semen
      quality is associated to fecundity. Therefore, it would be sensible to advise men
      to abstain from smoking to avoid decreased fecundity.

PMID- 16966352
TI  - Expression and regulation of heme oxygenase isozymes in the developing mouse
      cortex.
AB  - Heme oxygenase (HO), the rate-limiting enzyme in heme degradation, plays a role
      in neonatal jaundice. Understanding the regulation of the developmental
      expression patterns of the two HO isozymes, HO-1 and HO-2, is essential for
      targeting HO to control pathologic jaundice, and uncovering the fundamental role
      that they play in mammalian development. Here we characterized the ontogeny of HO
      1 and HO-2 expression in the developing mouse cortex by in vivo bioluminescence
      imaging, quantitative RT-PCR, and Western blot. HO-2, the predominant isoform in
      the adult cortex, was relatively stable throughout all ages. HO-1 was observed to
      be progressively down-regulated in an age-related manner. HO-1 expression in the
      adult cortex was also the lowest among the eight adult tissues analyzed. Because
      there is a 283-bp CpG island region in the HO-1 promoter, we hypothesized that
      methylation of the island is responsible for the age-related HO-1 down-regulation
      in the cortex. Methylation status was assessed using regular and quantitative
      methylation-specific PCR and the CpG island was found to be hypomethylated at all
      ages. Therefore, we conclude that HO-1 gene expression in the cortex is
      developmentally-regulated and that methylation of the HO-1 CpG island is not
      associated with the down-regulation of the gene.

PMID- 16966351
TI  - Iron deficiency in infancy predicts altered serum prolactin response 10 years
      later.
AB  - Serum prolactin may reflect CNS dopaminergic function. Because iron deficiency
      (ID) alters brain dopamine in rats, serum prolactin levels were previously
      investigated in infants with varied iron status. High serum prolactin levels
      correlated with behaviors typical of chronic ID. The objective of this study was
      to determine the effect of infant iron status on serum prolactin levels after a
      stressor in early adolescence. One hundred fifty-nine of 191 children enrolled in
      infancy (chronic ID, n = 46; good iron comparison group, n = 113) had serum
      prolactin measurements after catheter placement at 11-14 y of age. Serum
      prolactin levels were compared by sex, pubertal status and infant iron status and
      the pattern of change over time was compared by infant iron status controlling
      for pubertal stage and background factors. Males and less mature adolescents had
      lower serum prolactin concentrations than females and more mature adolescents.
      Controlling for these factors, the serum prolactin response pattern differed
      significantly by infant iron status. Serum prolactin declined earlier for the
      chronic ID group. In conclusion, an altered serum prolactin response pattern was
      observed 10 y after chronic ID in infancy and may suggest a long-lasting effect
      of ID on the regulation of prolactin.

PMID- 16966353
TI  - Altered placental and fetal expression of IGFs and IGF-binding proteins
      associated with intrauterine growth restriction in fetal sheep during early and
      mid-pregnancy.
AB  - The insulin-like growth factors (IGFs) are postulated to be altered in
      association with the development of intrauterine growth restriction (IUGR). The
      present studies examined placental and fetal hepatic mRNA concentration of
      components of the IGF system at two time points (55 and 90 d gestational age,
      dGA; Term 147 dGA) in a hyperthermia (HT)-induced sheep model of placental
      insufficiency-IUGR. Maternal plasma insulin and IGF-I were constant at 55 and 90
      dGA and were unaffected by treatment. Umbilical vein insulin concentrations
      tended to be reduced at 90 dGA following HT exposure. Caruncle IGF-I mRNA was
      increased at 90 dGA in HT placentae (p < 0.05), while cotyledon concentrations
      were constant over gestation and unaltered by treatment. In control cotyledons,
      IGF-II mRNA concentration increased (p < 0.01) and IGFBP-3 decreased between 55
      and 90 dGA (p < 0.01). Cotyledon IGF-II and caruncle IGFBP-4 mRNA were elevated
      at 55 dGA in HT placentae compared with control (p < 0.01 and p < 0.05
      respectively). Fetal hepatic IGF-I, IGFBP-2, -3 and -4 concentrations rose over
      gestation (p < 0.05), but there were no treatment effects. These data suggest
      that changes in placental IGF expression in early and mid gestation may
      predispose the pregnancy to placental insufficiency, resulting in inadequate
      substrate supply to the developing fetus later in gestation.

PMID- 16966354
TI  - Ureteric jet Doppler waveform and bladder wall thickness in children with
      nocturnal enuresis.
AB  - To test the hypothesis that the presence of nocturnal enuresis is related to
      increased frequency of immature vesicoureteric function, which is further
      associated with detrusor overactivity, we compared the incidence of immature
      monophasic ureteric jet in children with and without nocturnal enuresis. The
      relationship between monophasic ureteric jet Doppler wave form and bladder wall
      thickness was further explored in the enuresis group. Ultrasound examinations
      were performed in 511 children suffering from nocturnal enuresis and 266 normal
      controls. Doppler wave forms of the ureteric jet on each side and the bladder
      wall thickness after voiding were recorded. Standard urodynamic studies were
      obtained in 203 enuretic children for correlations with ultrasound findings.
      There was a significant increase in the incidence of monophasic ureteric jet
      waveforms in enuretic children when compared with the controls (19.2% versus 6.4%
      on the right side, 19.2% versus 8.3% on the left side, all p < 0.01).
      Furthermore, immature monophasic waveforms were more commonly seen in the
      enuretic group with markedly thickened bladder wall. Enuretic children with
      bilateral immature ureteric jet waveforms and markedly thickened bladder wall
      showed multiple significant urodynamic abnormalities (p < 0.05). The above
      observations could be accounted for by immaturity of both vesicoureteric junction
      and detrusor muscle.

PMID- 16966355
TI  - Expression of uncoupling protein 3 and GLUT4 gene in skeletal muscle of preterm
      newborns: possible control by AMP-activated protein kinase.
AB  - We seek to understand the mechanism for the delayed postnatal switch between
      glycolytic and oxidative metabolism in preterm newborns. Our previous study
      [Brauner et al. (Pediatr Res 53: 691-697, 2003)] suggested impaired postnatal
      recruitment of the gene for mitochondrial uncoupling protein 3 (UCP3) by
      nutritional lipids in skeletal muscle of neonates delivered before approximately
      26 wk of gestation. UCP3 is linked to lipid oxidation and may be involved in the
      defective development of energy metabolism in skeletal muscles of very preterm
      newborns. In extension of our previous study, autopsy samples of musculus
      quadriceps femoris from 40 mostly preterm neonates and 5 fetuses were used for
      quantification of transcripts for UCP3, GLUT4, and their transcriptional
      regulator, AMP-activated protein kinase (AMPK). The new analysis confirmed the
      defect in the recruitment of the UCP3 gene expression by lipids in very preterm
      neonates. It also suggested involvement of AMPK in the control of expression of
      both metabolic genes, UCP3 and GLUT4, in the skeletal muscle of the newborns.
      Experiments on adult C57BL/6J mice confirmed the relationships between the
      transcripts and supported the involvement of AMPK in the control of UCP3 gene
      expression.

PMID- 16966356
TI  - Impaired T-lymphocyte proliferation function in biliary atresia patients with
      chronic cholestatic jaundice after a Kasai operation.
AB  - To investigate the association between chronic cholestatic jaundice, systemic
      immunity, and various infectious complications in patients with biliary atresia
      (BA), we performed a survey of the systemic immune function in 30 children with
      BA. Patients were divided into a jaundice group (total serum bilirubin > or = 2
      mg/dL for >6 mo) and control group (total serum bilirubin <2 mg/dL for >6 mo)
      with comparable age. Patients were tested for serum immunoglobulin and complement
      levels, mitogen response, interleukin (IL)-4, IL-5, and interferon-gamma
      production after phytohemagglutinin (PHA) stimulation, blood cell and lymphocyte
      subpopulation counts, phagocytic function, and leukocyte adhesion complex. They
      were then followed prospectively for 6 mo, and severe infectious complications
      requiring hospitalization were recorded. Compared with jaundice-free patients, T
      lymphocyte proliferation function, determined by PHA mitogen test was
      significantly lower (p = 0.02) in BA patients with chronic cholestatic jaundice
      after a Kasai operation. During the study period, patients with chronic
      cholestatic jaundice had a higher risk of severe infectious complications than
      their jaundice-free counterparts (risk ratio = 5.87; p = 0.001). In conclusion,
      BA patients with chronic cholestatic jaundice are associated with impairment of T
      lymphocyte proliferation and increased incidence of severe infectious
      complications.

PMID- 16966357
TI  - Impact of ibuprofen therapy in the outcome of experimental pneumococcal acute
      otitis media treated with amoxicillin or erythromycin.
AB  - The impact of ibuprofen combined with amoxicillin or erythromycin for therapy of
      penicillin-resistant pneumococcal acute otitis media (AOM) was evaluated in a
      gerbil model. Ibuprofen (at 2.5 or 7.5 mg/kg, orally) and/or amoxicillin or
      erythromycin (5 mg/kg each, s.c.) were administered at 5 h (early therapy, as
      single-dose regimen) or at 18 h (delayed therapy, five doses) postinoculation
      (PI). Each antibiotic alone and combined with ibuprofen was more effective
      administered as early regimen than as delayed treatment when evaluating the
      presence of otorrhea, otoscopic aspect, culture-positive and bacterial counts in
      middle ear (ME) samples, and loss of body weight. There was a trend for a better
      bacteriological outcome in animals receiving amoxicillin or erythromycin and
      ibuprofen, especially with the high dose. Such a dose of ibuprofen, associated
      with each antibiotic regimen, also preserved the animal well-being, avoiding a
      great weight loss in comparison to those receiving the antibiotic alone but a
      statistically significant difference was only observed for animals receiving
      delayed therapy with erythromycin and high-dose ibuprofen. In conclusion,
      ibuprofen combined with antibiotics seemed to improve the outcome of this
      experimental pneumococcal AOM.

PMID- 16966358
TI  - Augur--a computational pipeline for whole genome microbial surface protein
      prediction and classification.
AB  - The analysis of protein function is a challenge and a major bottleneck towards
      well-annotated and analysed microbial genomes. In particular, bacterial surface
      proteins present an opportunity for pharmacological intervention and vaccine
      development. We present Augur, an automatic prediction pipeline that integrates
      major surface prediction algorithms and enables comparative analysis,
      classification and visualization for gram-positive bacteria on a genomic scale.
      AVAILABILITY: http://bioinfo.mikrobio.med.uni-giessen.de/augur

PMID- 16966359
TI  - SCAssign: a sparky extension for the NMR resonance assignment of aliphatic side
      chains of uniformly 13C,15N-labeled large proteins.
AB  - SCAssign (side-chain assignment) is a Sparky extension written in Python to
      assist the NMR resonance assignment of aliphatic side-chains of uniformly
      (13)C,(15)N-labeled large proteins. It is based on a general strategy recently
      developed in our laboratory that makes use of 4D (13)C,(15)N-edited NOESY, 3D MQ
      (H)CC(m)H(m)-TOCSY, and prior backbone assignments. The program runs on all
      operating systems for which Sparky is available, and is easy to install, setup
      and use. Not only can it accelerate the assignment process, it also allows
      assignments of weak NOEs in 4D NOESY, which used to be very difficult with manual
      approach. AVAILABILITY: The program, in the form of source code, is provided as
      free download at http://yangdw.science.nus.edu.sg/SCAssign. The website also
      contains installation guide, user manual and demonstrations recorded in Flash.

PMID- 16966360
TI  - Protein-RNA interactions: exploring binding patterns with a three-dimensional
      superposition analysis of high resolution structures.
AB  - MOTIVATION: The recognition of specific RNA sequences and structures by proteins
      is critical to our understanding of RNA processing, gene expression and viral
      replication. The diversity of RNA structures suggests that RNA recognition is
      substantially different than that of DNA. RESULTS: The atomic coordinates of 41
      protein-RNA complexes have been used to probe composite nucleoside binding
      pockets that form the structural and chemical underpinnings of base recognition.
      Composite nucleoside binding pockets were constructed using three-dimensional
      superpositions of each RNA nucleoside. Unlike protein-DNA interactions which are
      dominated by accessibility, RNA recognition frequently occurs in non-canonical
      and single-strand-like structures that allow interactions to occur from a much
      wider set of geometries and make fuller use of unique base shapes and hydrogen
      bonding ability. By constructing composites that include all van der Waals,
      hydrogen-bonding, stacking and general non-polar interactions made to a
      particular nucleoside, the strategies employed are made readily visible. Protein
      RNA interactions can result in the formation of a glove-like tight binding pocket
      around RNA bases, but the size, shape and non-polar binding patterns differ
      between specific RNA bases. We show that adenine can be distinguished from
      guanine based on the size and shape of the binding pocket and steric exclusion of
      the guanine N2 exocyclic amino group. The unique shape and hydrogen-bonding
      pattern for each RNA base allow proteins to make specific interactions through a
      very small number of contacts, as few as two in some cases. AVAILABILITY: The
      program ENTANGLE is available from http://www.bioc.rice.edu/~shamoo

PMID- 16966361
TI  - SPEED: a molecular-evolution-based database of mammalian orthologous groups.
AB  - MOTIVATION: The abundance of nucleotide sequence information available has
      expanded horizons of inquiry for molecular evolution; however, the full potential
      of whole-genome analysis has not been realized because of inadequate tools. Here,
      we present one of the first toolkits to aid multidisciplinary high-throughput
      analysis. SUMMARY: SPEED was created to integrate molecular evolutionary data
      with existing genetic resources and provide a straightforward user interface to
      17,352 orthologous gene groups, containing representatives from eight mammalian
      species and an avian outgroup. AVAILABILITY: See
      http://bioinfobase.umkc.edu/speed/ for access.

PMID- 16966362
TI  - Probabilistic inference of transcription factor concentrations and gene-specific
      regulatory activities.
AB  - MOTIVATION: Quantitative estimation of the regulatory relationship between
      transcription factors and genes is a fundamental stepping stone when trying to
      develop models of cellular processes. Recent experimental high-throughput
      techniques, such as Chromatin Immunoprecipitation (ChIP) provide important
      information about the architecture of the regulatory networks in the cell.
      However, it is very difficult to measure the concentration levels of
      transcription factor proteins and determine their regulatory effect on gene
      transcription. It is therefore an important computational challenge to infer
      these quantities using gene expression data and network architecture data.
      RESULTS: We develop a probabilistic state space model that allows genome-wide
      inference of both transcription factor protein concentrations and their effect on
      the transcription rates of each target gene from microarray data. We use
      variational inference techniques to learn the model parameters and perform
      posterior inference of protein concentrations and regulatory strengths. The
      probabilistic nature of the model also means that we can associate credibility
      intervals to our estimates, as well as providing a tool to detect which binding
      events lead to significant regulation. We demonstrate our model on artificial
      data and on two yeast datasets in which the network structure has previously been
      obtained using ChIP data. Predictions from our model are consistent with the
      underlying biology and offer novel quantitative insights into the regulatory
      structure of the yeast cell. AVAILABILITY: MATLAB code is available from
      http://umber.sbs.man.ac.uk/resources/puma

PMID- 16966363
TI  - Support vector machine learning from heterogeneous data: an empirical analysis
      using protein sequence and structure.
AB  - MOTIVATION: Drawing inferences from large, heterogeneous sets of biological data
      requires a theoretical framework that is capable of representing, e.g. DNA and
      protein sequences, protein structures, microarray expression data, various types
      of interaction networks, etc. Recently, a class of algorithms known as kernel
      methods has emerged as a powerful framework for combining diverse types of data.
      The support vector machine (SVM) algorithm is the most popular kernel method, due
      to its theoretical underpinnings and strong empirical performance on a wide
      variety of classification tasks. Furthermore, several recently described
      extensions allow the SVM to assign relative weights to various datasets,
      depending upon their utilities in performing a given classification task.
      RESULTS: In this work, we empirically investigate the performance of the SVM on
      the task of inferring gene functional annotations from a combination of protein
      sequence and structure data. Our results suggest that the SVM is quite robust to
      noise in the input datasets. Consequently, in the presence of only two types of
      data, an SVM trained from an unweighted combination of datasets performs as well
      or better than a more sophisticated algorithm that assigns weights to individual
      data types. Indeed, for this simple case, we can demonstrate empirically that no
      solution is significantly better than the naive, unweighted average of the two
      datasets. On the other hand, when multiple noisy datasets are included in the
      experiment, then the naive approach fares worse than the weighted approach. Our
      results suggest that for many applications, a naive unweighted sum of kernels may
      be sufficient. AVAILABILITY: http://noble.gs.washington.edu/proj/seqstruct

PMID- 16966365
TI  - Management of neuromuscular dose limiting toxicity at the early stage of drug
      development.

PMID- 16966366
TI  - Phase I study of Aplidine in a dailyx5 one-hour infusion every 3 weeks in
      patients with solid tumors refractory to standard therapy. A National Cancer
      Institute of Canada Clinical Trials Group study: NCIC CTG IND 115.
AB  - BACKGROUND: Aplidine is a cyclic depsipeptide isolated from the marine tunicate
      Aplidium albicans. METHODS: This phase I study of Aplidine given as a 1-hour i.v.
      infusion daily for 5 days every 3 weeks was conducted in patients with refractory
      solid tumors. Objectives were to define the dose limiting toxicities, the maximal
      tolerated dose, and the recommended phase II dose. RESULTS: Thirty-seven patients
      were accrued on study. Doses ranged from 80 microg/m(2) to 1500 microg/m(2)/day.
      Eleven patients received more than three cycles of Aplidine. Dose-limiting
      toxicities occurred at 1500 microg/m(2) and 1350 microg/m(2)/day and consisted of
      nausea, vomiting, myalgia, fatigue, skin rash and diarrhea. Mild to moderate
      muscular pain and weakness was noted in patients treated with multiple cycles
      with no significant drug related neurotoxicity. Bone marrow toxicity was not
      observed. The recommended dose for phase II studies was 1200 microg/m(2) daily
      for 5 days, every 3 weeks. Pharmacokinetic studies performed during the first
      cycle demonstrated that therapeutic plasma levels of Aplidine are reachable well
      below the recommended dose. Nine patients with progressive disease at study entry
      had stable disease and two had minor responses, one in non-small cell lung cancer
      and one in colorectal cancer. CONCLUSIONS: Aplidine given at a dose of 1200
      microg/m(2) daily for 5 days, every 3 weeks is well tolerated with few severe
      adverse events. This schedule of Aplidine is under evaluation in phase II studies
      in hematological malignancies and solid tumors.

PMID- 16966367
TI  - Detailed analysis of a randomized phase III trial: can the tolerability of
      capecitabine plus docetaxel be improved without compromising its survival
      advantage?
AB  - BACKGROUND: In a phase III trial, 3-weekly capecitabine (1250 mg/m(2) twice daily
      days 1-14) plus docetaxel (75 mg/m(2) day 1) demonstrated significantly superior
      overall survival to 3-weekly docetaxel (100 mg/m(2) day 1). We report a
      retrospective analysis of the impact of capecitabine/docetaxel dose reduction on
      safety and efficacy. PATIENTS AND METHODS: Safety and efficacy data were analyzed
      retrospectively according to the actual doses of capecitabine and docetaxel
      administered. RESULTS: More patients receiving capecitabine/docetaxel (65%) had
      dose reductions for adverse events than docetaxel alone (35%). In most patients
      requiring dose reduction with the combination (80%), capecitabine and docetaxel
      were simultaneously reduced to 950 mg/m(2) and 55 mg/m(2), respectively.
      Subsequently, there were fewer cycles (17%) with grade 3/4 adverse events than
      with the full doses (34%). Time to progression and overall survival appeared to
      be similar in patients starting the second cycle with reduced doses of
      capecitabine/docetaxel and those who continued to receive full doses of
      capecitabine/docetaxel for at least the first four cycles. CONCLUSIONS:
      Capecitabine/docetaxel dosing flexibility allows management of side-effects
      without compromising efficacy. This retrospective analysis, as well as multiple
      phase II studies of taxanes with reduced-dose capecitabine, shows that reducing
      the starting dose of capecitabine with docetaxel is a reasonable strategy for the
      treatment of patients with metastatic breast cancer. In addition, reducing the
      dose of both agents may be appropriate.

PMID- 16966368
TI  - High incidence of non-neutropenic infections induced by rituximab plus
      fludarabine and associated with hypogammaglobulinemia: a frequently unrecognized
      and easily treatable complication.
AB  - BACKGROUND: Rituximab is associated with low incidence of hypogammaglobulinemia
      and little morbidity. Our experience with the combination of rituximab +
      chemotherapy suggested the opposite. PATIENTS AND METHODS: We analyzed our
      experience with rituximab plus chemotherapy in 97 patients to determine:
      frequency and type of non-neutropenic infection (NNI); frequency and type of
      hypogammaglobulinemia; response to gammaglobulin therapy; and factors associated
      with NNI. RESULTS: We observed 40 episodes of NNI in 19 of 97 (20%) patients. By
      3 years, 43% of patients treated with rituximab + chemotherapy were projected to
      have developed at least one NNI. Of 19 with NNI, 15 had Ig levels studied and all
      15 had hypogammaglobulinemia. Most frequently affected Ig were IgG (14 of 15) and
      IgM (13 of 14). IgA was usually spared (six of 14 cases affected). NNIs observed
      were 18 bronchitis, 16 sinusitis, four pneumonias, three otitis media, two fevers
      of unknown origin (FUOs) and three herpes zoster. Hospitalization was required in
      seven of 19. Ten received gammaglobulin infusions and all responded promptly.
      Gammaglobulin was given only when NNIs recurred. We examined sex, age, histology,
      type of rituximab-chemotherapy (fludarabine + rituximab versus other chemotherapy
      + rituximab) for correlation with NNI. CONCLUSIONS: Indolent histology, female
      sex and fludarabine + rituximab significantly correlated with frequency of NNI
      but multivariate analysis picked fludarabine + rituximab followed by female
      gender as the only two independent variables predictive of NNI.

PMID- 16966369
TI  - Differential role of basal keratinocytes in UV-induced immunosuppression and skin
      cancer.
AB  - Cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs) comprise
      major UV-induced photolesions. If left unrepaired, these lesions can induce
      mutations and skin cancer, which is facilitated by UV-induced immunosuppression.
      Yet the contribution of lesion and cell type specificity to the harmful
      biological effects of UV exposure remains currently unclear. Using a series of
      photolyase-transgenic mice to ubiquitously remove either CPDs or 6-4PPs from all
      cells in the mouse skin or selectively from basal keratinocytes, we show that the
      majority of UV-induced acute effects to require the presence of CPDs in basal
      keratinocytes in the mouse skin. At the fundamental level of gene expression,
      CPDs induce the expression of genes associated with repair and recombinational
      processing of DNA damage, as well as apoptosis and a response to stress. At the
      organismal level, photolyase-mediated removal of CPDs, but not 6-4PPs, from the
      genome of only basal keratinocytes substantially diminishes the incidence of skin
      tumors; however, it does not affect the UVB-mediated immunosuppression. Taken
      together, these findings reveal a differential role of basal keratinocytes in
      these processes, providing novel insights into the skin's acute and chronic
      responses to UV in a lesion- and cell-type-specific manner.

PMID- 16966370
TI  - Placental but not heart defects are associated with elevated hypoxia-inducible
      factor alpha levels in mice lacking prolyl hydroxylase domain protein 2.
AB  - PHD1, PHD2, and PHD3 are prolyl hydroxylase domain proteins that regulate the
      stability of hypoxia-inducible factor alpha subunits (HIF-alpha). To determine
      the roles of individual PHDs during mouse development, we disrupted all three Phd
      genes and found that Phd2(-/-) embryos died between embryonic days 12.5 and 14.5
      whereas Phd1(-/-) or Phd3(-/-) mice were apparently normal. In Phd2(-/-) mice,
      severe placental and heart defects preceded embryonic death. Placental defects
      included significantly reduced labyrinthine branching morphogenesis, widespread
      penetration of the labyrinth by spongiotrophoblasts, and abnormal distribution of
      trophoblast giant cells. The expression of several trophoblast markers was also
      altered, including an increase in the spongiotrophoblast marker Mash2 and
      decreases in the labyrinthine markers Tfeb and Gcm1. In the heart, trabeculae
      were poorly developed, the myocardium was remarkably thinner, and
      interventricular septum was incompletely formed. Surprisingly, while there were
      significant global increases in HIF-alpha protein levels in the placenta and the
      embryo proper, there was no specific HIF-alpha increase in the heart. Taken
      together, these data indicate that among all three PHD proteins, PHD2 is uniquely
      essential during mouse embryogenesis.

PMID- 16966371
TI  - Transcriptional regulation is affected by subnuclear targeting of reporter
      plasmids to PML nuclear bodies.
AB  - Whereas the PML protein has been reported to have both transcriptional
      coactivator and corepressor potential, the contribution of the PML nuclear body
      (PML NB) itself to transcriptional regulation is not well understood. Here we
      demonstrate that plasmid DNA artificially tethered to PML or the PML NB-targeting
      domain of Sp100 is preferentially localized to PML NBs. Using the tethering
      technique, we targeted a simian virus 40 promoter-driven luciferase reporter
      plasmid to PML NBs, resulting in the repression of the transgene transcriptional
      activity. Conversely, the tethering of a cytomegalovirus promoter-containing
      reporter plasmid resulted in activation. Targeting a minimal eukaryotic promoter
      did not affect its activity. The expression of targeted promoters could be
      modulated by altering the cellular concentration of PML NB components, including
      Sp100 and isoforms of the PML protein. Finally, we demonstrate that ICP0, the
      promiscuous herpes simplex virus transactivator, increases the level of
      transcriptional activation of plasmid DNA tethered to the PML NB. We conclude
      that when PML NB components are artificially tethered to reporter plasmids, the
      PML NB contributes to the regulation of the tethered DNA in a promoter-dependent
      manner. Our findings demonstrate that transient transcription assays are
      sensitive to the subnuclear localization of the transgene plasmid.

PMID- 16966372
TI  - Lck regulates the threshold of activation in primary T cells, while both Lck and
      Fyn contribute to the magnitude of the extracellular signal-related kinase
      response.
AB  - The src family kinases p56lck (Lck) and p59fyn (Fyn) are the most proximal
      signaling molecules to be activated downstream of the T-cell receptor. Using an
      inducible transgenic model, we can regulate the expression of Lck in primary T
      cells and ask how the signaling cascade and differentiation potential are
      affected by the absence or the presence of reduced levels of Lck. We show that in
      naive T cells, Lck controls the threshold of activation by preferentially
      regulating multiple signaling pathways that result in the mobilization of Ca2+
      through activation of phospholipase C-gamma and protein kinase C as well as
      activation of the extracellular signal-regulated kinase (ERK)/mitogen-activated
      protein kinase (MAPK) pathway. Fyn is also able to stimulate the ERK/MAPK pathway
      in primary T cells but has little influence on the mobilization of Ca2+. Only Lck
      efficiently stimulates production of diacylglycerol and therefore RasGRP1
      recruitment to the plasma membrane and phosphorylation of Shc, suggesting that
      Fyn activates ERK via a different upstream signaling route. Finally, we show that
      signals through Lck are essential for the development of T-cell-effector
      potential, particularly for effective cytokine transcription.

PMID- 16966373
TI  - Apoptosome-independent activation of the lysosomal cell death pathway by caspase
      9.
AB  - The apoptosome, a heptameric complex of Apaf-1, cytochrome c, and caspase-9, has
      been considered indispensable for the activation of caspase-9 during apoptosis.
      By using a large panel of genetically modified murine embryonic fibroblasts, we
      show here that, in response to tumor necrosis factor (TNF), caspase-8 cleaves and
      activates caspase-9 in an apoptosome-independent manner. Interestingly, caspase-8
      cleaved caspase-9 induced lysosomal membrane permeabilization but failed to
      activate the effector caspases whereas apoptosome-dependent activation of caspase
      9 could trigger both events. Consistent with the ability of TNF to activate the
      intrinsic apoptosis pathway and the caspase-9-dependent lysosomal cell death
      pathway in parallel, their individual inhibition conferred only a modest delay in
      TNF-induced cell death whereas simultaneous inhibition of both pathways was
      required to achieve protection comparable to that observed in caspase-9-deficient
      cells. Taken together, the findings indicate that caspase-9 plays a dual role in
      cell death signaling, as an activator of effector caspases and lysosomal membrane
      permeabilization.

PMID- 16966374
TI  - O-GlcNAc integrates the proteasome and transcriptome to regulate nuclear hormone
      receptors.
AB  - Mechanisms controlling nuclear hormone receptors are a central question to
      mammalian developmental and disease processes. Herein, we show that a subtle
      increase in O-GlcNAc levels inhibits activation of nuclear hormone receptors. In
      vivo, increased levels of O-GlcNAc impair estrogen receptor activation and cause
      a decrease in mammary ductal side-branching morphogenesis associated with loss of
      progesterone receptors. Increased O-GlcNAc levels suppress transcriptional
      expression of coactivators and of the nuclear hormone receptors themselves.
      Surprisingly, increased O-GlcNAc levels are also associated with increased
      transcription of genes encoding corepressor proteins NCoR and SMRT. The
      association of the enzyme O-GlcNAc transferase with these corepressors
      contributes to specific regulation of nuclear hormone receptors by O-GlcNAc.
      Overall, transcriptional inhibition is related to the integrated effect of O
      GlcNAc by direct modification of critical elements of the transcriptome and
      indirectly through O-GlcNAc modification of the proteasome.

PMID- 16966375
TI  - Requirement of hCenexin for proper mitotic functions of polo-like kinase 1 at the
      centrosomes.
AB  - Outer dense fiber 2 (Odf2) was initially identified as a major component of sperm
      tail cytoskeleton and later was suggested to be a widespread component of
      centrosomal scaffold that preferentially associates with the appendages of the
      mother centrioles in somatic cells. Here we report the identification of two Odf2
      related centrosomal components, hCenexin1 and hCenexin1 variant 1, that possess a
      unique C-terminal extension. Our results showed that hCenexin1 is the major
      isoform expressed in HeLa cells, whereas hOdf2 is not detectably expressed.
      Mammalian polo-like kinase 1 (Plk1) is critical for proper mitotic progression,
      and its association with the centrosome is important for microtubule nucleation
      and function. Interestingly, depletion of hCenexin1 by RNA interference (RNAi)
      delocalized Plk1 from the centrosomes and the C-terminal extension of hCenexin1
      was crucial to recruit Plk1 to the centrosomes through a direct interaction with
      the polo-box domain of Plk1. Consistent with these findings, the hCenexin1 RNAi
      cells exhibited weakened gamma-tubulin localization and chromosome segregation
      defects. We propose that hCenexin1 is a critical centrosomal component whose C
      terminal extension is required for proper recruitment of Plk1 and other
      components crucial for normal mitosis. Our results further suggest that the anti
      Odf2 immunoreactive centrosomal antigen previously detected in non-germ line
      cells is likely hCenexin1.

PMID- 16966376
TI  - DNA repair protein involved in heart and blood development.
AB  - Apurinic/apyrimidinic endonuclease 1, a key enzyme in repairing abasic sites in
      DNA, is an embryonic lethal in mice. We are examining its role in embryogenesis
      in zebra fish. Zebra fish contain two genomic copies (zfAPEX1a and zfAPEX1b) with
      identical coding sequences. zfAPEX1b lacks introns. Recombinant protein (ZAP1) is
      highly homologous with and has the same enzymatic properties as its human
      orthologue. ZAP1 is highly expressed throughout development. Embryos
      microinjected with morpholino oligonucleotide (MO) targeting the translation
      start site die at approximately the midblastula transition (MBT) without
      apoptosis. They are rescued with mRNA for human wild-type APEX1 but not for APEX1
      encoding endonuclease-defective protein. Rescued embryos develop dysmorphic
      hearts, pericardial edema, few erythrocytes, small eyes, and abnormal notochords.
      Although the hearts in rescued embryos form defective loops ranging from no loop
      to one that is abnormally shaped, cardiac myosin (cmlc2) is present and
      contraction occurs. Embryos microinjected with MO targeting zfAPEX1a intron-exon
      junctions also pass the MBT with similar abnormalities. We conclude that AP
      endonuclease 1 is involved in both repairing DNA and regulating specific early
      stages of embryonic development.

PMID- 16966377
TI  - The HBP1 transcriptional repressor participates in RAS-induced premature
      senescence.
AB  - Oncogene-mediated premature senescence has emerged as a potential tumor
      suppressive mechanism in early cancer transitions. Previous work shows that RAS
      and p38 MAPK participate in premature senescence, but transcriptional effectors
      have not been identified. Here, we demonstrate that the HBP1 transcriptional
      repressor participates in RAS- and p38 MAPK-induced premature senescence. In cell
      lines, we had previously isolated HBP1 as a retinoblastoma (RB) target but have
      determined that it functions as a proliferation regulator by inhibiting oncogenic
      pathways as a transcriptional repressor. In primary cells, the results indicate
      that HBP1 is a necessary component of premature senescence by RAS and p38 MAPK.
      Similarly, a knockdown of WIP1 (a p38 MAPK phosphatase) induced premature
      senescence that also required HBP1. Furthermore, HBP1 requires regulation by RB,
      in which few transcriptional regulators for premature senescence have been shown.
      Together, the data suggest a model in which RAS and p38 MAPK signaling engage
      HBP1 and RB to trigger premature senescence. As an initial step toward clinical
      relevance, a bioinformatics approach shows that the relative expression levels of
      HBP1 and WIP1 correlated with decreased relapse-free survival in breast cancer
      patients. Together, these studies highlight p38 MAPK, HBP1, and RB as important
      components for a premature-senescence pathway with possible clinical relevance to
      breast cancer.

PMID- 16966378
TI  - Skeletal muscle-selective knockout of LKB1 increases insulin sensitivity,
      improves glucose homeostasis, and decreases TRB3.
AB  - LKB1 is a tumor suppressor that may also be fundamental to cell metabolism, since
      LKB1 phosphorylates and activates the energy sensing enzyme AMPK. We generated
      muscle-specific LKB1 knockout (MLKB1KO) mice, and surprisingly, found that a lack
      of LKB1 in skeletal muscle enhanced insulin sensitivity, as evidenced by
      decreased fasting glucose and insulin concentrations, improved glucose tolerance,
      increased muscle glucose uptake in vivo, and increased glucose utilization during
      a hyperinsulinemic-euglycemic clamp. MLKB1KO mice had increased insulin
      stimulated Akt phosphorylation and a > 80% decrease in muscle expression of TRB3,
      a recently identified Akt inhibitor. Akt/TRB3 binding was present in skeletal
      muscle, and overexpression of TRB3 in C2C12 myoblasts significantly reduced Akt
      phosphorylation. These results demonstrate that skeletal muscle LKB1 is a
      negative regulator of insulin sensitivity and glucose homeostasis. LKB1-mediated
      TRB3 expression provides a novel link between LKB1 and Akt, critical kinases
      involved in both tumor genesis and cell metabolism.

PMID- 16966379
TI  - A new function in translocation for the mitochondrial i-AAA protease Yme1: import
      of polynucleotide phosphorylase into the intermembrane space.
AB  - Polynucleotide phosphorylase (PNPase) is an exoribonuclease and poly(A)
      polymerase postulated to function in the cytosol and mitochondrial matrix. Prior
      overexpression studies resulted in PNPase localization to both the cytosol and
      mitochondria, concurrent with cytosolic RNA degradation and pleiotropic cellular
      effects, including growth inhibition and apoptosis, that may not reflect a
      physiologic role for endogenous PNPase. We therefore conducted a mechanistic
      study of PNPase biogenesis in the mitochondrion. Interestingly, PNPase is
      localized to the intermembrane space by a novel import pathway. PNPase has a
      typical N-terminal targeting sequence that is cleaved by the matrix processing
      peptidase when PNPase engaged the TIM23 translocon at the inner membrane. The i
      AAA protease Yme1 mediated translocation of PNPase into the intermembrane space
      but did not degrade PNPase. In a yeast strain deleted for Yme1 and expressing
      PNPase, nonimported PNPase accumulated in the cytosol, confirming an in vivo role
      for Yme1 in PNPase maturation. PNPase localization to the mitochondrial
      intermembrane space suggests a unique role distinct from its highly conserved
      function in RNA processing in chloroplasts and bacteria. Furthermore, Yme1 has a
      new function in protein translocation, indicating that the intermembrane space
      harbors diverse pathways for protein translocation.

PMID- 16966380
TI  - Phosphorylation of Rad55 on serines 2, 8, and 14 is required for efficient
      homologous recombination in the recovery of stalled replication forks.
AB  - DNA damage checkpoints coordinate the cellular response to genotoxic stress and
      arrest the cell cycle in response to DNA damage and replication fork stalling.
      Homologous recombination is a ubiquitous pathway for the repair of DNA double
      stranded breaks and other checkpoint-inducing lesions. Moreover, homologous
      recombination is involved in postreplicative tolerance of DNA damage and the
      recovery of DNA replication after replication fork stalling. Here, we show that
      the phosphorylation on serines 2, 8, and 14 (S2,8,14) of the Rad55 protein is
      specifically required for survival as well as for normal growth under genome-wide
      genotoxic stress. Rad55 is a Rad51 paralog in Saccharomyces cerevisiae and
      functions in the assembly of the Rad51 filament, a central intermediate in
      recombinational DNA repair. Phosphorylation-defective rad55-S2,8,14A mutants
      display a very slow traversal of S phase under DNA-damaging conditions, which is
      likely due to the slower recovery of stalled replication forks or the slower
      repair of replication-associated DNA damage. These results suggest that Rad55
      S2,8,14 phosphorylation activates recombinational repair, allowing for faster
      recovery after genotoxic stress.

PMID- 16966381
TI  - Mammalian polynucleotide phosphorylase is an intermembrane space RNase that
      maintains mitochondrial homeostasis.
AB  - We recently identified polynucleotide phosphorylase (PNPase) as a potential
      binding partner for the TCL1 oncoprotein. Mammalian PNPase exhibits
      exoribonuclease and poly(A) polymerase activities, and PNPase overexpression
      inhibits cell growth, induces apoptosis, and stimulates proinflammatory cytokine
      production. A physiologic connection for these anticancer effects and
      overexpression is difficult to reconcile with the presumed mitochondrial matrix
      localization for endogenous PNPase, prompting this study. Here we show that basal
      and interferon-beta-induced PNPase was efficiently imported into energized
      mitochondria with coupled processing of the N-terminal targeting sequence. Once
      imported, PNPase localized to the intermembrane space (IMS) as a peripheral
      membrane protein in a multimeric complex. Apoptotic stimuli caused PNPase
      mobilization following cytochrome c release, which supported an IMS localization
      and provided a potential route for interactions with cytosolic TCL1. Consistent
      with its IMS localization, PNPase knockdown with RNA interference did not affect
      mitochondrial RNA levels. However, PNPase reduction impaired mitochondrial
      electrochemical membrane potential, decreased respiratory chain activity, and was
      correlated with altered mitochondrial morphology. This resulted in FoF1-ATP
      synthase instability, impaired ATP generation, lactate accumulation, and AMP
      kinase phosphorylation with reduced cell proliferation. Combined, the data
      demonstrate an unexpected IMS localization and a key role for PNPase in
      maintaining mitochondrial homeostasis.

PMID- 16966382
TI  - Control of G2/M transition by Drosophila Fos.
AB  - The transcription factors of the Fos family have long been associated with the
      control of cell proliferation, although the molecular and cellular mechanisms
      that mediate this function are poorly understood. We investigated the
      contributions of Fos to the cell cycle and cell growth control using Drosophila
      imaginal discs as a genetically accessible system. The RNA interference-mediated
      inhibition of Fos in proliferating cells of the wing and eye discs resulted in a
      specific defect in the G2-to-M-phase transition, while cell growth remained
      unimpaired, resulting in a marked reduction in organ size. Consistent with the
      conclusion that Fos is required for mitosis, we identified cyclin B as a direct
      transcriptional target of Fos in Drosophila melanogaster, with Fos binding to a
      region upstream of the cyclin B gene in vivo and cyclin B mRNA being specifically
      reduced under Fos loss-of-function conditions.

PMID- 16966383
TI  - IRF-1 deficiency skews the differentiation of dendritic cells toward plasmacytoid
      and tolerogenic features.
AB  - Members of the IFN regulatory factors (IRFs) family are transcriptional
      regulators that play essential roles in the homeostasis and function of the
      immune system. Recent studies indicate a direct involvement of some members of
      the family in the development of different subsets of dendritic cells (DC). Here,
      we report that IRF-1 is a potent modulator of the development and functional
      maturation of DC. IRF-1-deficient mice (IRF-1(-/-)) exhibited a predominance of
      plasmacytoid DC and a selective reduction of conventional DC, especially the
      CD8alpha(+) subset. IRF-1(-/-) splenic DC were markedly impaired in their ability
      to produce proinflammatory cytokines such as IL-12. By contrast, they expressed
      high levels of IL-10, TGF-beta, and the tolerogenic enzyme indoleamine 2,3
      dioxygenase. As a consequence, IRF-1(-/-) DC were unable to undergo full
      maturation and retained plasmacytoid and tolerogenic characteristics following
      virus infection ex vivo and in vivo. Accordingly, DC from IRF-1(-/-) mice were
      less efficient in stimulating the proliferation of allogeneic T cells and
      instead, induced an IL-10-mediated, suppressive activity in allogeneic
      CD4(+)CD25(+) regulatory T cells. Together, these results indicate that IRF-1 is
      a key regulator of DC differentiation and maturation, exerting a variety of
      effects on the functional activation and tolerogenic potential of these cells.

PMID- 16966384
TI  - Effect of nicotine on IL-18-initiated immune response in human monocytes.
AB  - Nicotine is thought to inhibit the production of proinflammatory cytokines from
      macrophages through an anti-inflammatory pathway that is dependent on nicotinic
      acetylcholine receptor alpha7 subunit (alpha7-nAChR). IL-18, an important
      proinflammatory cytokine, is reported to induce the expression of adhesion
      molecules on monocytes, thus enhancing cell-to-cell interactions with T-cells and
      contributing to IL-18-initiated cytokine production. Accordingly, inhibition of
      IL-18 suppresses systemic inflammatory responses. In the present study, we found
      that nicotine inhibited the IL-18-enhanced expression of ICAM-1, B7.2, and CD40
      on monocytes, and the production of IL-12, IFN-gamma, and TNF-alpha by PBMC. A
      nonselective and a selective alpha7-nAChR antagonist, mecamylamine, and alpha
      bungarotoxin abolished the effects of nicotine, suggesting that this depends on
      alpha7-nAChR stimulation. It is reported that nicotine induces prostaglandinE2
      (PGE(2)) production in PBMC through the up-regulation of cyclooxygenase (COX)-2
      expression. PGE(2) is known to activate the EP2/EP4-receptor, leading to an
      increase in cyclic adenosine monophosphate (cAMP) levels and protein kinase A
      (PKA) activity. Consistent with this, we found that COX-2 and PKA inhibitors
      prevented the effects of nicotine on adhesion molecule expression and cytokine
      production, indicating that the mechanism of action of nicotine may be via
      endogenous PGE(2) production.

PMID- 16966385
TI  - Gene and protein characteristics reflect functional diversity of CD56dim and
      CD56bright NK cells.
AB  - Recent findings underline the role of NK cell subsets in regulating adaptive
      immunity. To define characteristics of NK cell subpopulations, purified CD56(dim)
      and CD56(bright) NK cells were analyzed by using gene chip arrays covering more
      than 39,000 transcripts. Gene profiling revealed resting NK cells to differ in
      respect to 473 transcripts with 176 exclusively expressed in CD56(dim) and 130
      solely in CD56(bright) NK cells. Results were compared with array analyses using
      mRNA obtained from activated CD56(dim) and CD56(bright) NK cells. In this
      approach, NK cell receptors, cytolytic molecules, adhesion structures, and
      chemokine ligands showed differential expression patterns in the two
      subpopulations. These data were validated using FACS, RT-qPCR, or cytokine bead
      array (CBA) techniques. Cytokines produced by CD56(dim) and CD56(bright) NK cells
      were determined using a protein array covering 79 different bioactive mediators.
      GDNF, IGFBP-1, EGF, and TIMP-2 were detected in both subsets. In contrast, IGFBP
      3 and IGF-1 were mainly produced by CD56(dim), while GM-CSF, TARC, and TGFbeta3
      were expressed by CD56(bright) NK cells. In summary, we report new characteristic
      features of CD56(dim) and CD56(bright) NK cells, further underscoring that they
      represent independent populations with functionally diverse capabilities. The
      information on NK cells generated in this study will help to define corresponding
      NK cell populations in other species that lack CD56 expression on NK cells, such
      as mice. This will subsequently lead to the establishment of suitable animal
      models for detailed analysis of NK cell populations in vivo.

PMID- 16966386
TI  - High mobility group box-1 protein induces the migration and activation of human
      dendritic cells and acts as an alarmin.
AB  - High mobility group box-1 (HMGB1) protein is a nonhistone, DNA-binding protein
      that plays a critical role in regulating gene transcription. Recently, HMGB1 has
      also been shown to act as a late mediator of endotoxic shock and to exert a
      variety of proinflammatory, extracellular activities. Here, we report that HMGB1
      simultaneously acts as a chemoattractant and activator of dendritic cells (DCs).
      HMGB1 induced the migration of monocyte-derived, immature DCs (Mo-iDCs) but not
      mature DCs. The chemotactic effect of HMGB1 on iDCs was pertussis toxin
      inhibitable and also inhibited by antibody against the receptor of advanced
      glycation end products (RAGE), suggesting that HMGB1 chemoattraction of iDCs is
      mediated by RAGE in a Gi protein-dependent manner. In addition, HMGB1 treatment
      of Mo-iDCs up-regulated DC surface markers (CD80, CD83, CD86, and HLA-A,B,C),
      enhanced DC production of cytokines (IL-6, CXCL8, IL-12p70, and TNF-alpha),
      switched DC chemokine responsiveness from CCL5-sensitive to CCL21-sensitive, and
      acquired the capacity to stimulate allogeneic T cell proliferation. Based on its
      dual DC-attracting and -activating activities as well as its reported capacity to
      promote an antigen-specific immune response, we consider HMGB1 to have the
      properties of an immune alarmin.

PMID- 16966387
TI  - Endurance exercise differentially stimulates heart and axial muscle development
      in zebrafish (Danio rerio).
AB  - Mechanical load is an important factor in the differentiation of cells and
      tissues. To investigate the effects of increased mechanical load on development
      of muscle and bone, zebrafish were subjected to endurance swim training for 6
      h/day for 10 wk starting at 14 days after fertilization. During the first 3 wk of
      training, trained fish showed transiently increased growth compared with
      untrained (control) fish. Increased expression of proliferating cell nuclear
      antigen suggests that this growth is realized in part through increased cell
      proliferation. Red and white axial muscle fiber diameter was not affected. Total
      cross-sectional area of red fibers, however, was increased. An improvement in
      aerobic muscle performance was supported by an increase in myoglobin expression.
      At the end of 10 wk of training, heart and axial muscle showed increased
      expression of the muscle growth factor myogenin and proliferating cell nuclear
      antigen, but there were major differences between cardiac and axial muscle. In
      axial muscle, expression of the "slow" types of myosin and troponin C was
      increased, together with expression of erythropoietin and myoglobin, which
      enhance oxygen transport, indicating a shift toward a slow aerobic phenotype. In
      contrast, the heart muscle shifts to a faster phenotype but does not become more
      aerobic. This suggests that endurance training differentially affects heart and
      axial muscle.

PMID- 16966388
TI  - Effects of cholesterol manipulation on the signaling of the human oxytocin
      receptor.
AB  - We have recently shown that oxytocin inhibits cell growth when the vast majority
      of oxytocin receptors (OTRs) are excluded from detergent-resistant membranes
      (DRMs; the biochemical counterpart of lipid rafts), but has a strong mitogenic
      effect when the receptors are targeted to these plasma membrane domains upon
      fusion with caveolin-2, a resident raft protein. The aim of this study was to
      investigate whether the manipulation of total cell cholesterol can influence OTR
      localization and signaling. Our data indicate that cholesterol depletion in HEK
      293 cells does not affect the signaling events mediated by the OTRs located
      outside DRMs. When treated with 2 mM methyl-beta-cyclodextrin (MbetaCD), the
      receptors remained outside and continued to inhibit cell growth. On the contrary,
      the MbetaCD treatment of cells expressing receptors fused to caveolin-2 led to
      their redistribution outside DRMs, and converted the receptor-mediated
      proliferative effect into cell growth inhibition. These data indicate that 1)
      once released from DRMs, the receptors fused to caveolin-2 signal exactly as wild
      type OTRs and 2) their DRM location is responsible for the specific OTR signaling
      leading to cell proliferation. Finally, we evaluated whether cholesterol loading
      could force the OTRs into lipid rafts and change their signaling, but, after cell
      treatment with an MbetaCD/cholesterol complex, receptor stimulation continued to
      lead to cell growth inhibition, thus indicating that increasing cell cholesterol
      levels is not sufficient per se to affect OTR signaling.

PMID- 16966389
TI  - Efferent projection from the bed nucleus of the stria terminalis suppresses
      activity of taste-responsive neurons in the hamster parabrachial nuclei.
AB  - Although the reciprocal projections between the bed nucleus of the stria
      terminalis (BNST) and the gustatory parabrachial nuclei (PbN) have been
      demonstrated neuroanatomically, there is no direct evidence showing that the
      projections from the PbN to the BNST carry taste information or that descending
      inputs from the BNST to the PbN modulate the activity of PbN gustatory neurons. A
      recent electrophysiological study has demonstrated that the BNST exerts
      modulatory influence on taste neurons in the nucleus of the solitary tract (NST),
      suggesting that the BNST may also modulate the activity of taste neurons in the
      PbN. In the present study, we recorded from 117 taste-responsive neurons in the
      PbN and examined their responsiveness to electrical stimulation of the BNST
      bilaterally. Thirteen neurons (11.1%) were antidromically invaded from the BNST,
      mostly from the ipsilateral side (12 cells), indicating that a subset of taste
      neurons in the PbN project their axons to the BNST. The BNST stimulation induced
      orthodromic responses on most of the PbN neurons: 115 out of 117 (98.3%),
      including all BNST projection units. This descending modulation on the PbN
      gustatory neurons was exclusively inhibitory. We also confirmed that activation
      of this efferent inhibitory projection from the BNST reduces taste responses of
      PbN neurons in all units tested. The BNST is part of the neural circuits that
      involve stress-associated feeding behavior. It is also known that brain stem
      gustatory nuclei, including the PbN, are associated with feeding behavior.
      Therefore, this neural substrate may be important in the stress-elicited
      alteration in ingestive behavior.

PMID- 16966390
TI  - A randomized comparison of nitrous oxide plus hematoma block versus ketamine plus
      midazolam for emergency department forearm fracture reduction in children.
AB  - OBJECTIVES: Ketamine provides effective and relatively safe sedation analgesia
      for reduction of fractures in children in the emergency department. However,
      prolonged recovery and adverse effects suggest the opportunity to develop
      alternative strategies. We compared the efficacy and adverse effects of
      ketamine/midazolam to those of nitrous oxide/hematoma block for analgesia and
      anxiolysis during forearm fracture reduction in children. METHODS: Children 5 to
      17 years of age were randomly assigned to receive intravenous ketamine (1
      mg/kg)/midazolam (0.1 mg/kg; max: 2.5 mg) or 50% nitrous oxide/50% oxygen and a
      hematoma block (2.5 mg/kg of 1% buffered lidocaine). All of the children received
      oral oxycodone 0.2 mg/kg (max: 15 mg) at triage > or = 45 minutes before
      reduction. Videotapes were obtained before (baseline), during (procedure), and
      after (recovery) reduction and scored using the Procedure Behavioral Checklist by
      an observer blinded to study purpose. The primary outcome measure was the mean
      change in Procedure Behavioral Checklist score from baseline to procedure, with
      greater change indicating greater procedure distress. Other outcome measures of
      efficacy included recovery times and visual analog scale scores to assess patient
      distress, parent report of child distress, and orthopedic surgeon satisfaction
      with sedation. Adverse effects were assessed during the emergency visit and by
      telephone 1 day after reduction. Data were analyzed using repeated measures, that
      is, analysis of variance, chi2, and t tests. RESULTS: There were 102 children
      (mean age: 9.0 +/- 3.0 years) who were randomly assigned. There was no difference
      in age, race, gender, and baseline Procedure Behavioral Checklist scores between
      ketamine/midazolam (55 subjects) and nitrous oxide/hematoma block (47 subjects).
      Mean changes in Procedure Behavioral Checklist scores were very small for both
      groups. The mean change in Procedure Behavioral Checklist was less for nitrous
      oxide/hematoma block, and patients and parents reported less pain during fracture
      reduction with nitrous oxide/hematoma block. Recovery times were markedly shorter
      for nitrous oxide/hematoma block compared with ketamine/midazolam. Orthopedic
      surgeons were similarly satisfied with the 2 regimens. Of the ketamine/midazolam
      subjects, 11% had O2 saturations < 94%. Other adverse effects occurred in both
      groups, but more often in ketamine/midazolam both during the emergency visit and
      at 1-day follow-up. CONCLUSIONS: In children who had received oral oxycodone,
      both nitrous oxide/hematoma block and ketamine/midazolam resulted in minimal
      increases in distress during forearm fracture reduction at the doses studied. The
      nitrous oxide/hematoma block regimen had fewer adverse effects and significantly
      less recovery time.

PMID- 16966391
TI  - Role of insurance for children with special health care needs: a synthesis of the
      evidence.
AB  - OBJECTIVE: Children with special health care needs constitute a particularly
      vulnerable subpopulation of children. Health insurance coverage has the potential
      to enhance access to care and improve the quality of life for these children
      while protecting their families from financially burdensome health care expenses.
      The purpose of this review is to assess and synthesize recent research in the
      peer-reviewed literature pertaining to the role of insurance for children with
      special health care needs. A marked increase in the volume of research on this
      topic makes this an opportune time to summarize these contributions and begin the
      process of formalizing an evidence base that can inform health policy decisions.
      Our intention is to further the evidence base by providing a literature-driven
      assessment of the role of health insurance in influencing access, utilization,
      satisfaction, quality, expenditures, and health outcomes for children with
      special health care needs. METHODS: A systematic literature review was conducted
      on the effects of insurance status, insurance type, and insurance features on
      access, utilization, satisfaction, quality, expenditures, and health status.
      RESULTS: The strongest evidence emerged for the positive effects of insurance on
      access and utilization. Limited evidence on the effect of insurance on
      satisfaction with care showed improved satisfaction ratings for the insured. The
      studies with findings relevant to out-of-pocket expenditures for insured versus
      uninsured children with special health care needs all found significantly higher
      out-of-pocket burden and financial problems among the uninsured. Evidence was
      mixed for the effects of insurance type (public or private) and insurance
      characteristics (eg, managed care or fee-for-service payment mechanisms) on
      outcomes. None of the studies that we reviewed attempted to assess the impact of
      health insurance on health outcomes. CONCLUSIONS: Our review of the literature
      found plentiful evidence demonstrating the positive and substantial impact of
      insurance on access and utilization. There also is clear evidence that insurance
      protects families against financially burdensome expenses. The evidence is less
      conclusive for satisfaction and quality and is nonexistent for health status.
      These latter outcomes should be the focus of future studies.

PMID- 16966392
TI  - Physical and mental health of mothers caring for a child with Rett syndrome.
AB  - OBJECTIVES: Our goal was to investigate the physical and mental health of mothers
      who care for a child with Rett syndrome. METHODS: We assessed maternal physical
      and mental health by using the SF-12 version 1 physical component summary and
      mental component summary scores as the outcome measures of interest. Mothers (n =
      135) of children with Rett syndrome completed the SF-12 measure as part of the
      Australian Rett Syndrome Study in 2002. The analysis investigated linear
      relationships between physical and mental health scores and maternal, family, and
      child characteristics. RESULTS: Mothers ranged in age from 21 to 60 years and
      their children from 3 to 27 years. Nearly half of these mothers (47.4%) indicated
      that they worked full-time or part-time outside the home, and 41% had a combined
      family (gross) income of <40,000 Australian dollars. The resultant model for
      physical health demonstrated that the following factors were positively
      associated with better maternal physical health: the mother working full-time or
      part-time outside the home, having some high school education, having private
      health insurance, the child not having breathing problems in the last 2 years,
      the child not having home-based structured therapy, and high scores on the Family
      Resource Scale (indicating adequacy of time resources for basic and family
      needs). The resultant model for mental health demonstrated that the following
      factors were positively associated with better maternal mental health: the mother
      working full-time or part-time outside the home, the child not having a fracture
      in the last 2 years, lesser reporting of facial stereotypes and involuntary
      facial movements, being in a well-adjusted marriage, and having low stress
      scores. CONCLUSIONS: Our study suggests that the most important predictors of
      maternal physical and emotional health are child behavior, caregiver demands, and
      family function.

PMID- 16966393
TI  - Comparison of N-terminal pro-B-type natriuretic peptide levels in critically ill
      children with sepsis versus acute left ventricular dysfunction.
AB  - OBJECTIVE: N-terminal pro-B-type natriuretic peptide has been shown to be a
      marker for cardiac dysfunction. The peptide level is also elevated in patients
      with sepsis. The purpose of this study was to assess whether N-terminal pro-B
      type natriuretic peptide levels can differentiate pediatric patients with sepsis
      from patients with acute left ventricular dysfunction. PATIENTS AND METHODS:
      Pediatric patients admitted to an ICU with sepsis or acute left ventricular
      dysfunction were evaluated clinically, and the grade of systemic inflammatory
      response syndrome was determined. Echocardiography was performed, and their
      levels of N-terminal pro-B-type natriuretic peptide were measured. The N-terminal
      pro-B-type natriuretic peptide level was also measured in patients with simple
      febrile illness. RESULTS: There were 10 patients with sepsis and 10 with acute
      left ventricular dysfunction. The age of the patients was similar, and systemic
      inflammatory-response syndrome grading was not different (sepsis: 2.8 +/- 0.4;
      acute left ventricular dysfunction: 2.6 +/- 0.7). N-terminal pro-B-type
      natriuretic peptide levels were elevated in patients with sepsis (median: 6064
      pg/mL; range: 495-60,417 pg/mL) but were significantly higher in patients with
      acute left ventricular dysfunction (median: 65,630 pg/mL; range: 15,125-288,000).
      The area under the receiver operating characteristics curve for the diagnosis of
      acute left ventricular dysfunction was 0.9. N-terminal pro-B-type natriuretic
      peptide levels of patients with sepsis and impaired systolic function were not
      different from those of patients with sepsis and normal systolic function. The N
      terminal pro-B-type natriuretic peptide levels of 20 patients with simple febrile
      illness were significantly lower. CONCLUSIONS: N-terminal pro-B-type natriuretic
      peptide levels are elevated in pediatric patients with sepsis but are higher in
      some, but not all, patients with acute left ventricular dysfunction. The overlap
      between N-terminal pro-B-type natriuretic peptide levels in sepsis and acute left
      ventricular dysfunction precludes the use of the peptide's level as a sole means
      to differentiate between these conditions. Excessive elevation in N-terminal pro
      B-type natriuretic peptide levels, however, suggests cardiac etiology for acute
      hemodynamic deterioration in infants and children.

PMID- 16966394
TI  - Novel Pseudomonas aeruginosa quorum-sensing inhibitors identified in an ultra
      high-throughput screen.
AB  - The opportunistic pathogen Pseudomonas aeruginosa has two complete acyl
      homoserine lactone (acyl-HSL) signaling systems, LasR-LasI and RhlR-RhlI. LasI
      catalyzes the synthesis of N-3-oxododecanoyl homoserine lactone (3OC12-HSL), and
      LasR is a transcription factor that requires 3OC12-HSL as a ligand. RhlI
      catalyzes the synthesis of N-butanoyl homoserine lactone (C4), and RhlR is a
      transcription factor that responds to C4. LasR and RhlR control the transcription
      of hundreds of P. aeruginosa genes, many of which are critical virulence
      determinants, and LasR is required for RhlR function. We developed an ultra-high
      throughput cell-based assay to screen a library of approximately 200,000
      compounds for inhibitors of LasR-dependent gene expression. Although the library
      contained a large variety of chemical structures, the two best inhibitors
      resembled the acyl-homoserine lactone molecule that normally binds to LasR. One
      compound, a tetrazole with a 12-carbon alkyl tail designated PD12, had a 50%
      inhibitory concentration (IC50) of 30 nM. The second compound, V-06-018, had an
      IC50 of 10 microM and is a phenyl ring with a 12-carbon alkyl tail. A microarray
      analysis showed that both compounds were general inhibitors of quorum sensing,
      i.e., the expression levels of most LasR-dependent genes were affected. Both
      compounds also inhibited the production of two quorum-sensing-dependent virulence
      factors, elastase and pyocyanin. These compounds should be useful for studies of
      LasR-dependent gene regulation and might serve as scaffolds for the
      identification of new quorum-sensing modulators.

PMID- 16966395
TI  - Interaction between miltefosine and amphotericin B: consequences for their
      activities towards intestinal epithelial cells and Leishmania donovani
      promastigotes in vitro.
AB  - The aim of this study was to evaluate the potential of a combination of two
      antileishmanial drugs, miltefosine (HePC) and amphotericin B (AMB), when
      administered by the oral route. Caco-2 cell monolayers were used as a validated
      in vitro model of the intestinal barrier and Leishmania donovani promastigotes as
      a model for evaluating the effect of the drug combination. Spectroscopic
      measurements demonstrated that HePC and AMB associate, leading to the formation
      of mixed aggregates in which AMB is solubilized as monomers. The incubation of
      the association of HePC and AMB with Caco-2 cell monolayers, at a concentration
      higher than 5 microM, led to (i) a reduction of the HePC-induced paracellular
      permeability enhancement in Caco-2 cell monolayers, (ii) an inhibition of the
      uptake of both drugs, and (iii) a decrease in the transepithelial transport of
      both drugs, suggesting that a pharmacokinetic antagonism between HePC and AMB
      could occur after their oral administration. However, the combination did not
      exhibit any antagonism or synergy in its antileishmanial activity. These results
      demonstrated a strong physicochemical interaction between HePC and AMB, depending
      on the concentration of each, which could have important consequences for their
      biological activities, if they are administered together.

PMID- 16966396
TI  - Variant Salmonella genomic island 1-L antibiotic resistance gene cluster in
      Salmonella enterica serovar Newport.
AB  - We report a new Salmonella genomic island 1 variant antibiotic resistance gene
      cluster called SGI1-L in a Salmonella enterica serovar Newport isolate containing
      a dfrA15 gene cassette conferring resistance to trimethoprim. The isolate carried
      another class 1 integron containing the aacC5 and aadA7 gene cassettes conferring
      resistance to gentamicin and streptomycin/spectinomycin, respectively.

PMID- 16966397
TI  - Peptide deformylase inhibitors as potent antimycobacterial agents.
AB  - Peptide deformylase (PDF) catalyzes the hydrolytic removal of the N-terminal
      formyl group from nascent proteins. This is an essential step in bacterial
      protein synthesis, making PDF an attractive target for antibacterial drug
      development. Essentiality of the def gene, encoding PDF from Mycobacterium
      tuberculosis, was demonstrated through genetic knockout experiments with
      Mycobacterium bovis BCG. PDF from M. tuberculosis strain H37Rv was cloned,
      expressed, and purified as an N-terminal histidine-tagged recombinant protein in
      Escherichia coli. A novel class of PDF inhibitors (PDF-I), the N-alkyl urea
      hydroxamic acids, were synthesized and evaluated for their activities against the
      M. tuberculosis PDF enzyme as well as their antimycobacterial effects. Several
      compounds from the new class had 50% inhibitory concentration (IC50) values of
      <100 nM. Some of the PDF-I displayed antibacterial activity against M.
      tuberculosis, including MDR strains with MIC90 values of <1 microM.
      Pharmacokinetic studies of potential leads showed that the compounds were orally
      bioavailable. Spontaneous resistance towards these inhibitors arose at a
      frequency of < or =5 x 10(-7) in M. bovis BCG. DNA sequence analysis of several
      spontaneous PDF-I-resistant mutants revealed that half of the mutants had
      acquired point mutations in their formyl methyltransferase gene (fmt), which
      formylated Met-tRNA. The results from this study validate M. tuberculosis PDF as
      a drug target and suggest that this class of compounds have the potential to be
      developed as novel antimycobacterial agents.

PMID- 16966398
TI  - A small subpopulation of blastospores in candida albicans biofilms exhibit
      resistance to amphotericin B associated with differential regulation of
      ergosterol and beta-1,6-glucan pathway genes.
AB  - The resistance of Candida albicans biofilms to a broad spectrum of antimicrobial
      agents has been well documented. Biofilms are known to be heterogeneous,
      consisting of microenvironments that may induce formation of resistant
      subpopulations. In this study we characterized one such subpopulation. C.
      albicans biofilms were cultured in a tubular flow cell (TF) for 36 h. The
      relatively large shear forces imposed by draining the TF removed most of the
      biofilm, which consisted of a tangled mass of filamentous forms with associated
      clusters of yeast forms. This portion of the biofilm exhibited the classic
      architecture and morphological heterogeneity of a C. albicans biofilm and was
      only slightly more resistant than either exponential- or stationary-phase
      planktonic cells. A submonolayer fraction of blastospores that remained on the
      substratum was resistant to 10 times the amphotericin B dose that eliminated the
      activity of the planktonic populations. A comparison between planktonic and
      biofilm populations of transcript abundance for genes coding for enzymes in the
      ergosterol (ERG1, -3, -5, -6, -9, -11, and -25) and beta-1,6-glucan (SKN and
      KRE1, -5, -6, and -9) pathways was performed by quantitative RT-PCR. The results
      indicate a possible association between the high level of resistance exhibited by
      the blastospore subpopulation and differential regulation of ERG1, ERG25, SKN1,
      and KRE1. We hypothesize that the resistance originates from a synergistic effect
      involving changes in both the cell membrane and the cell wall.

PMID- 16966399
TI  - Inhibition of multiple subtypes of influenza A virus in cell cultures with
      morpholino oligomers.
AB  - Peptide-conjugated phosphorodiamidate morpholino oligomers (P-PMO) are single
      stranded nucleic acid-like antisense agents that can reduce gene expression by
      sterically blocking complementary RNA sequence. P-PMO are water soluble and
      nuclease resistant, and they readily achieve uptake into cells in culture under
      standard conditions. Eight P-PMO, each 20 to 22 bases in length, were evaluated
      for their ability to inhibit influenza A virus (FLUAV) A/PR/8/34 (H1N1)
      replication in cell culture. The P-PMO were designed to base pair with FLUAV RNA
      sequences that are highly conserved across viral subtypes and considered critical
      to the FLUAV biological-cycle, such as gene segment termini and mRNA translation
      start site regions. Several P-PMO were highly efficacious, each reducing viral
      titer in a dose-responsive and sequence-specific manner in A/PR/8/34-infected
      cells. Two P-PMO, one designed to target the AUG translation start site region of
      PB1 mRNA and the other the 3'-terminal region of nucleoprotein viral genome RNA,
      also proved to be potent against several other FLUAV strains, including A/WSN/33
      (H1N1), A/Memphis/8/88 (H3N2), A/Eq/Miami/63 (H3N8), A/Eq/Prague/56 (H7N7), and
      the highly pathogenic A/Thailand/1(KAN-1)/04 (H5N1). The P-PMO exhibited minimal
      cytotoxicity in cell viability assays. High efficacy by two of the P-PMO against
      multiple FLUAV subtypes suggests that these oligomers represent a broad-spectrum
      therapeutic approach against a high percentage of known FLUAV strains.

PMID- 16966400
TI  - Molecular basis for enhanced activity of posaconazole against Absidia corymbifera
      and Rhizopus oryzae.
AB  - Posaconazole and itraconazole were more potent inhibitors of ergosterol
      synthesis, in both intact cells and cell extracts from Absidia corymbifera and
      Rhizopus oryzae, than voriconazole and fluconazole. Similarly, expression of
      CYP51 from R. oryzae in Saccharomyces cerevisiae significantly increased
      resistance to fluconazole and voriconazole but not to posaconazole and
      itraconazole.

PMID- 16966401
TI  - Multiple genetic elements carry the tetracycline resistance gene tet(W) in the
      animal pathogen Arcanobacterium pyogenes.
AB  - The tet(W) gene is associated with tetracycline resistance in a wide range of
      bacterial species, including obligately anaerobic rumen bacteria and isolates
      from the human gut and oral mucosa. However, little is known about how this gene
      is disseminated and the types of genetic elements it is carried on. We examined
      tetracycline-resistant isolates of the animal commensal and opportunistic
      pathogen Arcanobacterium pyogenes, all of which carried tet(W), and identified
      three genetic elements designated ATE-1, ATE-2, and ATE-3. These elements were
      found in 25%, 35%, and 60% of tetracycline-resistant isolates, respectively, with
      some strains carrying both ATE-2 and ATE-3. ATE-1 shows characteristics of a
      mobilizable transposon, and the tet(W) genes from strains carrying this element
      can be transferred at low frequencies between A. pyogenes strains. ATE-2 has
      characteristics of a simple transposon, carrying only the resistance gene and a
      transposase, while in ATE-3, the tet(W) gene is associated with a streptomycin
      resistance gene that is 100% identical at the DNA level with the aadE gene from
      the Campylobacter jejuni plasmid pCG8245. Both ATE-2 and ATE-3 show evidence of
      being carried on larger genetic elements, but conjugation to other strains was
      not observed under the conditions tested. ATE-1 was preferentially associated
      with A. pyogenes strains of bovine origin, while ATE-2 and ATE-3 elements were
      primarily found in porcine isolates, suggesting that these elements may circulate
      in different environments. In addition, four alleles of the tet(W) gene,
      primarily associated with different elements, were detected among A. pyogenes
      isolates.

PMID- 16966402
TI  - Utility of alkylaminoquinolinyl methanols as new antimalarial drugs.
AB  - Mefloquine has been one of the more valuable antimalarial drugs but has never
      reached its full clinical potential due to concerns about its neurologic side
      effects, its greater expense than that of other antimalarials, and the emergence
      of resistance. The commercial development of mefloquine superseded that of
      another quinolinyl methanol, WR030090, which was used as an experimental
      antimalarial drug by the U.S. Army in the 1970s. We evaluated a series of related
      2-phenyl-substituted alkylaminoquinolinyl methanols (AAQMs) for their potential
      as mefloquine replacement drugs based on a series of appropriate in vitro and in
      vivo efficacy and toxicology screens and the theoretical cost of goods.
      Generally, the AAQMs were less neurotoxic and exhibited greater antimalarial
      potency, and they are potentially cheaper than mefloquine, but they showed poorer
      metabolic stability and pharmacokinetics and the potential for phototoxicity.
      These differences in physiochemical and biological properties are attributable to
      the "opening" of the piperidine ring of the 4-position side chain. Modification
      of the most promising compound, WR069878, by substitution of an appropriate N
      functionality at the 4 position, optimization of quinoline ring substituents at
      the 6 and 7 positions, and deconjugation of quinoline and phenyl ring systems is
      anticipated to yield a valuable new antimalarial drug.

PMID- 16966403
TI  - Comparison of the serological responses to Moraxella catarrhalis immunoglobulin D
      binding outer membrane protein and the ubiquitous surface proteins A1 and A2.
AB  - Moraxella catarrhalis immunoglobulin D-binding protein (MID) is a complex antigen
      with unique immunoglobulin D (IgD)-binding, adhesion, and hemagglutination
      properties. Previous studies have shown that antibodies raised against MID764-913
      in rabbits inhibited M. catarrhalis adhesion to human alveolar epithelial cells,
      and immunization with MID764-913 resulted in an increased pulmonary clearance in
      a murine model. Strong immune responses against MID have also consistently been
      shown in humans. Here, the MID-specified IgG responses were compared to those of
      ubiquitous surface proteins A1 and A2 (UspA1/A2) using a series of recombinant
      fragments that spanned all three proteins. Sera were obtained from young
      children, aged 6 months to 1 year (n=8) and 2 to 3 years (n=15), and healthy
      adults (n=16). Acute- and convalescent-phase sera from chronic obstructive
      pulmonary disease (COPD) patients with M. catarrhalis infective exacerbations
      (n=23) were also analyzed. Young children, who are at risk of M. catarrhalis
      infection, had low levels of anti-MID and anti-UspA1/A2 antibodies. Healthy
      adults and the majority of COPD patients (16/23) had high levels of antibodies
      directed against, among others, the adhesive domain of MID and the fibronectin-
      and C3-binding domains of UspA1/A2. Among eight COPD patients in whom a rise in
      antibody levels could be detected, these functional domains were also the main
      regions targeted by the antibodies. In addition, human IgG directed against MID
      was bactericidal and anti-MID antibodies were additive to antibodies targeting
      UspA1/A2. Hence, the functional domains in these three antigens may have
      significant potential in a future vaccine against M. catarrhalis.

PMID- 16966404
TI  - Aberrant contraction of antigen-specific CD4 T cells after infection in the
      absence of gamma interferon or its receptor.
AB  - Several lines of evidence from different model systems suggest that gamma
      interferon (IFN-gamma) is an important regulator of T-cell contraction after
      antigen (Ag)-driven expansion. To specifically investigate the role of IFN-gamma
      in regulating the contraction of Ag-specific CD4 T cells, we infected IFN-gamma-/
      and IFN-gammaR1-/- mice with attenuated Listeria monocytogenes and monitored the
      numbers of Ag-specific CD4 T cells during the expansion, contraction, and memory
      phases of the immune response to infection. In the absence of IFN-gamma or the
      ligand-binding portion of its receptor, Ag-specific CD4 T cells exhibited normal
      expansion in numbers, but in both strains of deficient mice there was very little
      decrease in the number of Ag-specific CD4 T cells even at time points later than
      day 90 after infection. This significant delay in contraction was not due to
      prolonged infection, since mice treated with antibiotics to conclusively
      eliminate infection exhibited the same defect in contraction. In addition to
      altering the number of Ag-specific CD4 T cells, the absence of IFN-gamma
      signaling also changed the phenotype of cells generated after infection. IFN
      gammaR1-/- Ag-specific CD4 T cells reacquired expression of CD127 more quickly
      than wild-type cells, and more IFN-gammaR1-/- CD4 T cells were capable of
      producing both IFN-gamma and interleukin 2 following Ag stimulation. From these
      data we conclude that IFN-gamma regulates the contraction, phenotype, and
      function of Ag-specific CD4 T cells generated after infection.

PMID- 16966405
TI  - Ganglioside molecular mimicry and its pathological roles in Guillain-Barre
      syndrome and related diseases.

PMID- 16966406
TI  - Expression of Pseudomonas aeruginosa toxin ExoS effectively induces apoptosis in
      host cells.
AB  - Pseudomonas aeruginosa is an opportunistic bacterial pathogen that primarily
      infects immunocompromised individuals and patients with cystic fibrosis. Invasive
      strains of P. aeruginosa are known to induce apoptosis at a high frequency in
      HeLa cells and in many other cell lines, a process that is dependent on the ADP
      ribosylation (ADPRT) activity of a type III secreted protein ExoS. In our
      previous report, it was proposed that P. aeruginosa secreting ExoS, upon
      infection, shuts down host cell survival signal pathways by inhibiting ERK1/2 and
      p38 activation, and it activates proapoptotic pathways through activation of
      JNK1/2, leading ultimately to cytochrome c release and activation of caspases. In
      this study, we demonstrate that the expression of ExoS in HeLa cells by
      eukaryotic expression vector effectively caused apoptosis in an ADPRT activity
      dependent manner, indicating that ExoS alone is sufficient to trigger apoptotic
      death of host cells independent of any other bacterial factors. By expressing an
      EGFP-ExoS fusion protein, we were able to directly correlate the death of HeLa
      cells with the presence of intracellular ExoS and further proved the dependence
      of this process on both JNK activation and mitochondrial proapoptotic event. The
      cellular pathway responsible for the ExoS-induced cytotoxicity appears to be well
      conserved, since the expression of the ADPRT-competent ExoS also induced rapid
      cell death in the Drosophila melanogaster S2 cell lines. The presented study not
      only highlights the ability of ExoS ADPRT to modulate host cell signaling,
      eventually leading to apoptosis, but also establishes ExoS as a valuable tool, in
      principle, for the elucidation of apoptosis mechanisms.

PMID- 16966407
TI  - Role of lgtC in resistance of nontypeable Haemophilus influenzae strain R2866 to
      human serum.
AB  - We are investigating a nontypeable Haemophilus influenzae (NTHI) strain, R2866,
      isolated from a child with meningitis. R2866 is unusually resistant to killing by
      normal human serum. The serum 50% inhibitory concentration (IC50) for this strain
      is 18%, approaching that of encapsulated H. influenzae. R3392 is a derivative of
      R2866 that was found to have increased sensitivity to human serum (IC50, 1.5%).
      Analysis of tetrameric repeat regions within lipooligosaccharide (LOS)
      biosynthetic genes in both strains indicated that the glycosyltransferase gene
      lgtC was out of frame ("off") in most colonies of R3392 but in frame with its
      start codon ("on") in most colonies of the parent. We sought antigenic and
      biochemical evidence for modification of the LOS structure. In a whole-cell
      enzyme-linked immunosorbent assay, strain R3392 displayed reduced binding of the
      Galalpha1,4Gal-specific monoclonal antibody 4C4. Mass spectrometry analysis of
      LOS from strain R2866 indicated that the primary oligosaccharide glycoform
      contained four heptose and four hexose residues, while that of R3392 contained
      four heptose and three hexose residues. We conclude that the R2866 lgtC gene
      encodes a galactosyltransferase involved in synthesis of the 4C4 epitope, as in
      other strains, and that expression of lgtC is associated with the high-level
      serum resistance that has been observed for this strain. This is the first
      description of the genetic basis of high-level serum resistance in NTHI, as well
      as the first description of LOS composition in an NTHI strain for which the
      complete genome sequence has been determined.

PMID- 16966408
TI  - Structure of the expression site reveals global diversity in MSP2 (P44) variants
      in Anaplasma phagocytophilum.
AB  - Anaplasma phagocytophilum, a recently reclassified bacteria in the order
      Rickettsiales, infects many different animal species and causes an emerging tick
      borne disease of humans. The genome contains a large number of related genes and
      gene fragments encoding partial or apparently full-length outer membrane protein
      MSP2 (P44). Previous data using strains isolated from humans in the United States
      suggest that antigenic diversity results from RecF-mediated conversion of a
      single MSP2 (P44) expression site by partially homologous donor sequences.
      However, whether similar mechanisms operate in naturally infected animal species
      and the extent of global diversity in MSP2 (P44) are unknown. We analyzed the
      structure and diversity of the MSP2 (P44) expression site in strains derived from
      the United States and Europe and from infections of different animal species,
      including wildlife reservoirs. The results show that a syntenic expression site
      is present in all strains of A. phagocytophilum investigated. This genomic locus
      contained diverse MSP2 (P44) variants in all infected animals sampled, and
      variants also differed at different time points during infection. Although
      similar variants were found among different populations of U.S. origin, there was
      little sequence identity between U.S. strain variants (including genomic copies
      from a completely sequenced U.S. strain) and expression site variants infecting
      sheep and dogs in Norway and Sweden. Finally, the possibility that combinatorial
      mechanisms can generate additional diversity beyond the basic donor sequence
      repertoire is supported by the observation of shared sequence blocks throughout
      the MSP2 (P44) hypervariable region in reservoir hosts. These data suggest
      similar genetic mechanisms for A. phagocytophilum variation in all hosts but
      worldwide diversity of the MSP2 (P44) outer membrane protein.

PMID- 16966409
TI  - Human monoclonal antibodies directed against toxins A and B prevent Clostridium
      difficile-induced mortality in hamsters.
AB  - Clostridium difficile is the leading cause of nosocomial antibiotic-associated
      diarrhea, and recent outbreaks of strains with increased virulence underscore the
      importance of identifying novel approaches to treat and prevent relapse of
      Clostridium difficile-associated diarrhea (CDAD). CDAD pathology is induced by
      two exotoxins, toxin A and toxin B, which have been shown to be cytotoxic and, in
      the case of toxin A, enterotoxic. In this report we describe fully human
      monoclonal antibodies (HuMAbs) that neutralize these toxins and prevent disease
      in hamsters. Transgenic mice carrying human immunoglobulin genes were used to
      isolate HuMAbs that neutralize the cytotoxic effects of either toxin A or toxin B
      in cell-based in vitro neutralization assays. Three anti-toxin A HuMAbs (3H2,
      CDA1, and 1B11) could all inhibit the enterotoxicity of toxin A in mouse
      intestinal loops and the in vivo toxicity in a systemic mouse model. Four anti
      toxin B HuMAbs (MDX-1388, 103-174, 1G10, and 2A11) could neutralize cytotoxicity
      in vitro, although systemic toxicity in the mouse could not be neutralized. Anti
      toxin A HuMAb CDA1 and anti-toxin B HuMAb MDX-1388 were tested in the well
      established hamster model of C. difficile disease. CDA1 alone resulted in a
      statistically significant reduction of mortality in hamsters; however, the
      combination treatment offered enhanced protection. Compared to controls,
      combination therapy reduced mortality from 100% to 45% (P<0.0001) in the primary
      disease hamster model and from 78% to 32% (P<0.0001) in the less stringent
      relapse model.

PMID- 16966410
TI  - Ascaris suum-derived products suppress mucosal allergic inflammation in an
      interleukin-10-independent manner via interference with dendritic cell function.
AB  - We have previously demonstrated that protection from allergic inflammation by
      Ascaris suum infection was characterized by a global increase in interleukin-10
      (IL-10) and the development of protective CD4(+)/CD25(+) T cells (L. Schopf, S.
      Luccioli, V. Bundoc, P. Justice, C. C. Chan, B. J. Wetzel, H. H. Norris, J. F.
      Urban, Jr., and A. Keane-Myers, Investig. Ophthalmol. Vis. Sci. 46:2772-2780,
      2005). Here, we used A. suum pseudocoelomic fluid (PCF) in lieu of infection to
      define molecular mechanisms of allergic protection in a mouse model of allergic
      inflammation. Mice were sensitized with ragweed (RW) and PCF (RW/PCF), PCF alone,
      or RW alone and then challenged intratracheally, intranasally, and supraocularly
      with RW. Histological examination of the eyes and lungs, analysis of the
      bronchoalveolar lavage fluid (BALF), and characterization of ex vivo cytokine
      responses were performed to determine allergic inflammatory responses. RW/PCF
      treated mice had suppressed allergic immune responses compared to mice given RW
      alone. To investigate whether IL-10 was involved in PCF-mediated allergic
      protection, similar experiments were performed using mice genetically deficient
      for IL-10. Persistent protection from allergic disease was observed in the
      absence of IL-10, indicating the primary mechanism of PCF protection is IL-10
      independent. Ex vivo and in vitro analysis of PCF-treated dendritic cells (DC)
      demonstrated reduced activation receptor expression and cytokine production in
      response to either RW or lipopolysaccharide stimulation. These findings extend
      previous studies that showed infection with A. suum alters expression of allergic
      disease and suggest that PCF can contribute to this effect by interference with
      DC function.

PMID- 16966411
TI  - Use of protein microarrays to define the humoral immune response in leprosy
      patients and identification of disease-state-specific antigenic profiles.
AB  - Although the global prevalence of leprosy has decreased over the last few decades
      due to an effective multidrug regimen, large numbers of new cases are still being
      reported, raising questions as to the ability to identify patients likely to
      spread disease and the effects of chemotherapy on the overall incidence of
      leprosy. This can partially be attributed to the lack of diagnostic markers for
      different clinical states of the disease and the consequent implementation of
      differential, optimal drug therapeutic strategies. Accordingly, comparative
      bioinformatics and Mycobacterium leprae protein microarrays were applied to
      investigate whether leprosy patients with different clinical forms of the disease
      can be categorized based on differential humoral immune response patterns.
      Evaluation of sera from 20 clinically diagnosed leprosy patients using native
      protein and recombinant protein microarrays revealed unique disease-specific,
      humoral reactivity patterns. Statistical analysis of the serological patterns
      yielded distinct groups that correlated with phenolic glycolipid I reactivity and
      clinical diagnosis, thus demonstrating that leprosy patients, including those
      diagnosed with the paucibacillary, tuberculoid form of disease, can be classified
      based on humoral reactivity to a subset of M. leprae protein antigens produced in
      recombinant form.

PMID- 16966412
TI  - Early gamma interferon and interleukin-2 responses to vaccination predict the
      late resting memory in malaria-naive and malaria-exposed individuals.
AB  - Two different cell populations respond to potent T-cell-inducing vaccinations.
      The induction and loss of effector cells can be seen using an ex vivo enzyme
      linked immunospot (ELISPOT) assay, but the more durable resting memory response
      is demonstrable by a cultured ELISPOT assay. The relationship of the early
      effector response to durable resting memory is incompletely understood. Effector
      phenotype is usually identified by gamma interferon (IFN-gamma) production, but
      interleukin-2 (IL-2) has been specifically linked to the differentiation of
      memory cells. Here, IFN-gamma- and IL-2-secreting effector cells were identified
      by an ex vivo ELISPOT assay 1 week after vaccination and compared with the
      resting memory responses detected by a cultured ELISPOT assay 3 months later. The
      different kinetics and induction of IL-2 by different vaccines and natural
      exposure are described. Furthermore, both early IFN-gamma and IL-2 production
      independently predicted subsequent memory responses at 3 months in malaria-naive
      volunteers, but only IFN-gamma predicted memory in malaria-exposed volunteers.
      However, dual ELISPOT assays were also performed on malaria-exposed volunteers to
      identify cells producing both cytokines simultaneously. This demonstrated that
      double-cytokine-producing cells were highly predictive of memory. This assay may
      be useful in predicting vaccinations most likely to generate stable, long-term
      memory responses.

PMID- 16966413
TI  - Immunization with live Neisseria lactamica protects mice against meningococcal
      challenge and can elicit serum bactericidal antibodies.
AB  - Natural immunity against Neisseria meningitidis is thought to develop following
      nasopharyngeal colonization with this bacterium or other microbes expressing
      cross-reactive antigens. Neisseria lactamica is a commensal of the upper
      respiratory tract which is often carried by infants and young children;
      epidemiological evidence indicates that colonization with this bacterium can
      elicit serum bactericidal activity (SBA) against Neisseria meningitidis, the most
      validated correlate of protective immunity. Here we demonstrate experimentally
      that immunization of mice with live N. lactamica protects animals against lethal
      meningococcal challenge and that some, but not all, strains of N. lactamica
      elicit detectable SBA in immunized animals regardless of the serogroup of N.
      meningitidis. While it is unlikely that immunization with live N. lactamica will
      be implemented as a vaccine against meningococcal disease, understanding the
      basis for the induction of cross-protective immunity and SBA should be valuable
      in the design of subunit vaccines for the prevention of this important human
      infection.

PMID- 16966414
TI  - Tumor necrosis factor alpha- and inducible nitric oxide synthase-producing
      dendritic cells are rapidly recruited to the bladder in urinary tract infection
      but are dispensable for bacterial clearance.
AB  - The role of dendritic cells (DC) in urinary tract infections (UTI) is unknown.
      These cells contribute directly to the innate defense against various viral and
      bacterial infections. Here, we studied their role in UTI using an experimental
      model induced by transurethral instillation of the uropathogenic Escherichia coli
      (UPEC) strain 536 into C57BL/6 mice. While few DC were found in the uninfected
      bladder, many had been recruited after 24 h, mostly to the submucosa and
      uroepithelium. They expressed markers of activation and maturation and exhibited
      the CD11b+ F4/80+ CD8- Gr-1- myeloid subtype. Also, tumor necrosis factor alpha
      (TNF-alpha)- and inducible nitric oxide synthase (iNOS)-producing CD11bINT DC
      (Tip-DC) were detected, which recently were proposed to be critical in the
      defense against bacterial infections. However, Tip-DC-deficient CCR2-/- mice did
      not show reduced clearance of UPEC from the infected bladder. Moreover, clearance
      was also unimpaired in CD11c-DTR mice depleted of all DC by injection of
      diphtheria toxin. This may be explained by the abundance of granulocytes and of
      iNOS- and TNF-alpha-producing non-DC that were able to replace Tip-DC
      functionality. These findings demonstrate that some of the abundant DC recruited
      in UTI contributed innate immune effector functions, which were, however,
      dispensable in the microenvironment of the bladder.

PMID- 16966415
TI  - Complex role of hemoglobin and hemoglobin-haptoglobin binding proteins in
      Haemophilus influenzae virulence in the infant rat model of invasive infection.
AB  - Haemophilus influenzae requires an exogenous heme source for aerobic growth in
      vitro. Hemoglobin or hemoglobin-haptoglobin satisfies this requirement. Heme
      acquisition from hemoglobin-haptoglobin is mediated by proteins encoded by hgp
      genes. Both Hgps and additional proteins, including those encoded by the hxu
      operon, provide independent pathways for hemoglobin utilization. Recently we
      showed that deletion of the set of three hgp genes from a nontypeable strain (86
      028NP) of H. influenzae attenuated virulence in the chinchilla otitis media model
      of noninvasive disease. The present study was undertaken to investigate the role
      of the hgp genes in virulence of the wild-type serotype b clinical isolate HI689
      in the infant rat model of hematogenous meningitis, an established model of
      invasive disease requiring aerobic growth. Bacteremia of high titer and long
      duration (>14 days) and histopathologically confirmed meningitis occurred in >95%
      of infant rats challenged at 5 days of age with strain HI689. While mutations
      disrupting either the Hgp- or Hxu-mediated pathway of heme acquisition had no
      effect on virulence in infant rats, an isogenic mutant deficient for both
      pathways was unable to sustain bacteremia or produce meningitis. In contrast,
      mutations disrupting either pathway decreased the limited ability of H.
      influenzae to initiate and sustain bacteremia in weanling rats. Biochemical and
      growth studies also indicated that infant rat plasma contains multiple heme
      sources that change with age. Taken together, these data indicate that both the
      hgp genes and the hxuC gene are virulence determinants in the rat model of human
      invasive disease.

PMID- 16966416
TI  - The action behind the words: embryonic stem cell research marches on.
AB  - Talk of policy has dominated talk of science for those interested in embryonic
      stem cell science. But research is continuing, and the advances are making clear
      why embryonic stem cells are such an important scientific and medical resource.

PMID- 16966417
TI  - A hitchhiker's guide to survival finally makes CENs.
AB  - Most strains of the yeast Saccharomyces cerevisiae contain many copies of a 2
      microm plasmid, a selfish autonomously replicating DNA that relies on two
      different mechanisms to ensure its survival. One of these mechanisms involves the
      high fidelity segregation of the plasmids to daughter cells during cell division,
      a property that is starkly reminiscent of centromeres. A new study reported in
      this issue (see Hajra et al. on p. 779) demonstrates that this high fidelity is
      achieved by the 2-microm plasmid, effectively recruiting the centromeric histone
      Cse4 from its host yeast cell to forge its own centromere and finally revealing
      how the 2-microm plasmid has survived in budding yeasts over millions of years.

PMID- 16966418
TI  - Direct measurement of the lamellipodial protrusive force in a migrating cell.
AB  - There has been a great deal of interest in the mechanism of lamellipodial
      protrusion (Pollard, T., and G. Borisy. 2003. Cell. 112:453-465). However, one of
      this mechanism's endpoints, the force of protrusion, has never been directly
      measured. We place an atomic force microscopy cantilever in the path of a
      migrating keratocyte. The deflection of the cantilever, which occurs over a
      period of approximately 10 s, provides a direct measure of the force exerted by
      the lamellipodial leading edge. Stall forces are consistent with approximately
      100 polymerizing actin filaments per micrometer of the leading edge, each working
      as an elastic Brownian ratchet and generating a force of several piconewtons.
      However, the force-velocity curves obtained from this measurement, in which
      velocity drops sharply under very small loads, is not sensitive to low loading
      forces, and finally stalls rapidly at large loads, are not consistent with
      current theoretical models for the actin polymerization force. Rather, the curves
      indicate that the protrusive force generation is a complex multiphase process
      involving actin and adhesion dynamics.

PMID- 16966419
TI  - Specific and flexible roles of heparan sulfate modifications in Drosophila FGF
      signaling.
AB  - Specific sulfation sequence of heparan sulfate (HS) contributes to the selective
      interaction between HS and various proteins in vitro. To clarify the in vivo
      importance of HS fine structures, we characterized the functions of the
      Drosophila HS 2-O and 6-O sulfotransferase (Hs2st and Hs6st) genes in FGF
      mediated tracheal formation. We found that mutations in Hs2st or Hs6st had
      unexpectedly little effect on tracheal morphogenesis. Structural analysis of
      mutant HS revealed not only a loss of corresponding sulfation, but also a
      compensatory increase of sulfation at other positions, which maintains the level
      of HS total charge. The restricted phenotypes of Hsst mutants are ascribed to
      this compensation because FGF signaling is strongly disrupted by Hs2st; Hs6st
      double mutation, or by overexpression of 6-O sulfatase, an extracellular enzyme
      which removes 6-O sulfate groups without increasing 2-O sulfation. These findings
      suggest that the overall sulfation level is more important than strictly defined
      HS fine structures for FGF signaling in some developmental contexts.

PMID- 16966420
TI  - The centromere-specific histone variant Cse4p (CENP-A) is essential for
      functional chromatin architecture at the yeast 2-microm circle partitioning locus
      and promotes equal plasmid segregation.
AB  - The centromere protein A homologue Cse4p is required for kinetochore assembly and
      faithful chromosome segregation in Saccharomyces cerevisiae. It has been regarded
      as the exquisite hallmark of centromeric chromatin. We demonstrate that Cse4
      resides at the partitioning locus STB of the 2-microm plasmid. Cse4p-STB
      association is absolutely dependent on the plasmid partitioning proteins Rep1p
      and Rep2p and the integrity of the mitotic spindle. The kinetochore mutation
      ndc10-1 excludes Cse4p from centromeres without dislodging it from STB. Cse4p-STB
      association lasts from G1/S through late telophase during the cell cycle. The
      release of Cse4p from STB chromatin is likely mediated through spindle
      disassembly. A lack of functional Cse4p disrupts the remodeling of STB chromatin
      by the RSC2 complex, negates Rep2p binding and cohesin assembly at STB, and
      causes plasmid missegregation. Poaching of a specific histone variant by the
      plasmid to mark its partitioning locus with a centromere tag reveals yet another
      one of the molecular trickeries it performs for achieving chromosome- like
      fidelity in segregation.

PMID- 16966421
TI  - Mouse Emi2 is required to enter meiosis II by reestablishing cyclin B1 during
      interkinesis.
AB  - During interkinesis, a metaphase II (MetII) spindle is built immediately after
      the completion of meiosis I. Oocytes then remain MetII arrested until
      fertilization. In mouse, we find that early mitotic inhibitor 2 (Emi2), which is
      an anaphase-promoting complex inhibitor, is involved in both the establishment
      and the maintenance of MetII arrest. In MetII oocytes, Emi2 needs to be degraded
      for oocytes to exit meiosis, and such degradation, as visualized by fluorescent
      protein tagging, occurred tens of minutes ahead of cyclin B1. Emi2 antisense
      morpholino knockdown during oocyte maturation did not affect polar body (PB)
      extrusion. However, in interkinesis the central spindle microtubules from meiosis
      I persisted for a short time, and a MetII spindle failed to assemble. The
      chromatin in the oocyte quickly decondensed and a nucleus formed. All of these
      effects were caused by the essential role of Emi2 in stabilizing cyclin B1 after
      the first PB extrusion because in Emi2 knockdown oocytes a MetII spindle was
      recovered by Emi2 rescue or by expression of nondegradable cyclin B1 after
      meiosis I.

PMID- 16966422
TI  - Ca2+ store depletion causes STIM1 to accumulate in ER regions closely associated
      with the plasma membrane.
AB  - Stromal interacting molecule 1 (STIM1), reported to be an endoplasmic reticulum
      (ER) Ca(2+) sensor controlling store-operated Ca(2+) entry, redistributes from a
      diffuse ER localization into puncta at the cell periphery after store depletion.
      STIM1 redistribution is proposed to be necessary for Ca(2+) release-activated
      Ca(2+) (CRAC) channel activation, but it is unclear whether redistribution is
      rapid enough to play a causal role. Furthermore, the location of STIM1 puncta is
      uncertain, with recent reports supporting retention in the ER as well as
      insertion into the plasma membrane (PM). Using total internal reflection
      fluorescence (TIRF) microscopy and patch-clamp recording from single Jurkat
      cells, we show that STIM1 puncta form several seconds before CRAC channels open,
      supporting a causal role in channel activation. Fluorescence quenching and
      electron microscopy analysis reveal that puncta correspond to STIM1 accumulation
      in discrete subregions of junctional ER located 10-25 nm from the PM, without
      detectable insertion of STIM1 into the PM. Roughly one third of these ER-PM
      contacts form in response to store depletion. These studies identify an ER
      structure underlying store-operated Ca(2+) entry, whose extreme proximity to the
      PM may enable STIM1 to interact with CRAC channels or associated proteins.

PMID- 16966423
TI  - The elementary unit of store-operated Ca2+ entry: local activation of CRAC
      channels by STIM1 at ER-plasma membrane junctions.
AB  - The activation of store-operated Ca(2+) entry by Ca(2+) store depletion has long
      been hypothesized to occur via local interactions of the endoplasmic reticulum
      (ER) and plasma membrane, but the structure involved has never been identified.
      Store depletion causes the ER Ca(2+) sensor stromal interacting molecule 1
      (STIM1) to form puncta by accumulating in junctional ER located 10-25 nm from the
      plasma membrane (see Wu et al. on p. 803 of this issue). We have combined total
      internal reflection fluorescence (TIRF) microscopy and patch-clamp recording to
      localize STIM1 and sites of Ca(2+) influx through open Ca(2+) release-activated
      Ca(2+) (CRAC) channels in Jurkat T cells after store depletion. CRAC channels
      open only in the immediate vicinity of STIM1 puncta, restricting Ca(2+) entry to
      discrete sites comprising a small fraction of the cell surface. Orai1, an
      essential component of the CRAC channel, colocalizes with STIM1 after store
      depletion, providing a physical basis for the local activation of Ca(2+) influx.
      These studies reveal for the first time that STIM1 and Orai1 move in a
      coordinated fashion to form closely apposed clusters in the ER and plasma
      membranes, thereby creating the elementary unit of store-operated Ca(2+) entry.

PMID- 16966424
TI  - PKA-activated ApAF-ApC/EBP heterodimer is a key downstream effector of ApCREB and
      is necessary and sufficient for the consolidation of long-term facilitation.
AB  - Long-term memory requires transcriptional regulation by a combination of positive
      and negative transcription factors. Aplysia activating factor (ApAF) is known to
      be a positive transcription factor that forms heterodimers with ApC/EBP and
      ApCREB2. How these heterodimers are regulated and how they participate in the
      consolidation of long-term facilitation (LTF) has not, however, been
      characterized. We found that the functional activation of ApAF required
      phosphorylation of ApAF by PKA on Ser-266. In addition, ApAF lowered the
      threshold of LTF by forming a heterodimer with ApCREB2. Moreover, once activated
      by PKA, the ApAF-ApC/EBP heterodimer transactivates enhancer response element
      containing genes and can induce LTF in the absence of CRE- and CREB-mediated gene
      expression. Collectively, these results suggest that PKA-activated ApAF-ApC/EBP
      heterodimer is a core downstream effector of ApCREB in the consolidation of LTF.

PMID- 16966425
TI  - Role of fascin in filopodial protrusion.
AB  - In this study, the mechanisms of actin-bundling in filopodia were examined.
      Analysis of cellular localization of known actin cross-linking proteins in mouse
      melanoma B16F1 cells revealed that fascin was specifically localized along the
      entire length of all filopodia, whereas other actin cross-linkers were not. RNA
      interference of fascin reduced the number of filopodia, and remaining filopodia
      had abnormal morphology with wavy and loosely bundled actin organization.
      Dephosphorylation of serine 39 likely determined cellular filopodia frequency.
      The constitutively active fascin mutant S39A increased the number and length of
      filopodia, whereas the inactive fascin mutant S39E reduced filopodia frequency.
      Fluorescence recovery after photobleaching of GFP-tagged wild-type and S39A
      fascin showed that dephosphorylated fascin underwent rapid cycles of association
      to and dissociation from actin filaments in filopodia, with t(1/2) < 10 s. We
      propose that fascin is a key specific actin cross-linker, providing stiffness for
      filopodial bundles, and that its dynamic behavior allows for efficient
      coordination between elongation and bundling of filopodial actin filaments.

PMID- 16966426
TI  - RLIP76 (RalBP1) is an R-Ras effector that mediates adhesion-dependent Rac
      activation and cell migration.
AB  - The Ras family of small GTPases regulates cell proliferation, spreading,
      migration and apoptosis, and malignant transformation by binding to several
      protein effectors. One such GTPase, R-Ras, plays distinct roles in each of these
      processes, but to date, identified R-Ras effectors were shared with other Ras
      family members (e.g., H-Ras). We utilized a new database of Ras-interacting
      proteins to identify RLIP76 (RalBP1) as a novel R-Ras effector. RLIP76 binds
      directly to R-Ras in a GTP-dependent manner, but does not physically associate
      with the closely related paralogues H-Ras and Rap1A. RLIP76 is required for
      adhesion-induced Rac activation and the resulting cell spreading and migration,
      as well as for the ability of R-Ras to enhance these functions. RLIP76 regulates
      Rac activity through the adhesion-induced activation of Arf6 GTPase and
      activation of Arf6 bypasses the requirement for RLIP76 in Rac activation and cell
      spreading. Thus, we identify a novel R-Ras effector, RLIP76, which links R-Ras to
      adhesion-induced Rac activation through a GTPase cascade that mediates cell
      spreading and migration.

PMID- 16966427
TI  - Continuous recruitment of naive T cells contributes to heterogeneity of antiviral
      CD8 T cells during persistent infection.
AB  - Numerous microbes establish persistent infections, accompanied by antigen
      specific CD8 T cell activation. Pathogen-specific T cells in chronically infected
      hosts are often phenotypically and functionally variable, as well as distinct
      from T cells responding to nonpersistent infections; this phenotypic
      heterogeneity has been attributed to an ongoing reencounter with antigen.
      Paradoxically, maintenance of memory CD8 T cells to acutely resolved infections
      is antigen independent, whereas there is a dependence on antigen for T cell
      survival in chronically infected hosts. Using two chronic viral infections, we
      demonstrate that new naive antigen-specific CD8 T cells are primed after the
      acute phase of infection. These newly recruited T cells are phenotypically
      distinct from those primed earlier. Long-lived antiviral CD8 T cells are
      defective in self-renewal, and lack of thymic output results in the decline of
      virus-specific CD8 T cells, indicating that newly generated T cells preserve
      antiviral CD8 T cell populations during chronic infection. These findings reveal
      a novel role for antigen in maintaining virus-specific CD8 T cells during
      persistent infection and provide insight toward understanding T cell
      differentiation in chronic infection.

PMID- 16966428
TI  - The requirement for Notch signaling at the beta-selection checkpoint in vivo is
      absolute and independent of the pre-T cell receptor.
AB  - Genetic inactivation of Notch signaling in CD4(-)CD8(-) double-negative (DN)
      thymocytes was previously shown to impair T cell receptor (TCR) gene
      rearrangement and to cause a partial block in CD4(+)CD8(+) double-positive (DP)
      thymocyte development in mice. In contrast, in vitro cultures suggested that
      Notch was absolutely required for the generation of DP thymocytes independent of
      pre-TCR expression and activity. To resolve the respective role of Notch and the
      pre-TCR, we inhibited Notch-mediated transcriptional activation in vivo with a
      green fluorescent protein-tagged dominant-negative Mastermind-like 1 (DNMAML)
      that allowed us to track single cells incapable of Notch signaling. DNMAML
      expression in DN cells led to decreased production of DP thymocytes but only to a
      modest decrease in intracellular TCRbeta expression. DNMAML attenuated the pre
      TCR-associated increase in cell size and CD27 expression. TCRbeta or TCRalphabeta
      transgenes failed to rescue DNMAML-related defects. Intrathymic injections of
      DNMAML(-) or DNMAML(+) DN thymocytes revealed a complete DN/DP transition block,
      with production of DNMAML(+) DP thymocytes only from cells undergoing late Notch
      inactivation. These findings indicate that the Notch requirement during the beta
      selection checkpoint in vivo is absolute and independent of the pre-TCR, and it
      depends on transcriptional activation by Notch via the CSL/RBP-J-MAML complex.

PMID- 16966429
TI  - Essential roles of DC-derived IL-15 as a mediator of inflammatory responses in
      vivo.
AB  - Interleukin (IL)-15 is expressed in a variety of inflammatory diseases. However,
      the contribution of dendritic cell (DC)-derived IL-15 to the development of
      diseases is uncertain. Using established models of Propionibacterium acnes (P.
      acnes)- and zymosan-induced liver inflammation, we observed granuloma formation
      in the livers of wild-type (WT) and RAG-2(-/-) mice but not in those of IL-15(-/
      ) mice. We demonstrate that this is likely caused by an impaired sequential
      induction of IL-12, IFN-gamma, and chemokines necessary for monocyte migration.
      Likewise, lethal endotoxin shock was not induced in P. acnes- and zymosan-primed
      IL-15(-/-) mice or in WT mice treated with a new IL-15-neutralizing antibody. In
      both systems, proinflammatory cytokine production was impaired. Surprisingly,
      neither granuloma formation, lethal endotoxin shock, nor IL-15 production was
      induced in mice deficient for DCs, and adoptive transfer of WT but not IL-15(-/-)
      DCs restored the disease development in IL-15(-/-) mice. Collectively, these data
      indicate the importance of DC-derived IL-15 as a mediator of inflammatory
      responses in vivo.

PMID- 16966430
TI  - Persistent expression of autoantibodies in SLE patients in remission.
AB  - A majority of the antibodies expressed by nascent B cells in healthy humans are
      self-reactive, but most of these antibodies are removed from the repertoire
      during B cell development. In contrast, untreated systemic lupus erythematosus
      (SLE) patients fail to remove many of the self-reactive and polyreactive
      antibodies from the naive repertoire. Here, we report that SLE patients in
      clinical remission continue to produce elevated numbers of self-reactive and
      polyreactive antibodies in the mature naive B cell compartment, but the number of
      B cells expressing these antibodies is lower than in patients with active
      disease. Our finding that abnormal levels of self-reactive mature naive B cells
      persist in the majority of patients in clinical remission suggests that early
      checkpoint abnormalities are an integral feature of SLE.

PMID- 16966431
TI  - Primary glioblastomas express mesenchymal stem-like properties.
AB  - Glioblastoma is the most common and aggressive primary brain cancer. Recent
      isolation and characterization of brain tumor-initiating cells supports the
      concept that transformed neural stem cells may seed glioblastoma. We previously
      identified a wide array of mesenchymal tissue transcripts overexpressed in a
      broad set of primary glioblastoma (de novo) tumors but not in secondary
      glioblastoma (derived from lower-grade) tumors, low-grade astrocytomas, or normal
      brain tissues. Here, we extend this observation and show that a subset of primary
      glioblastoma tumors and their derived tumor lines express cellular and molecular
      markers that are associated with mesenchymal stem cells (MSC) and that
      glioblastoma cell cultures can be induced to differentiate into multiple
      mesenchymal lineage-like cell types. These findings suggest either that a subset
      of primary glioblastomas derive from transformed stem cells containing MSC-like
      properties and retain partial phenotypic aspects of a MSC nature in tumors or
      that glioblastomas activate a series of genes that result in mesenchymal
      properties of the cancer cells to effect sustained tumor growth and malignant
      progression.

PMID- 16966432
TI  - Honokiol potentiates apoptosis, suppresses osteoclastogenesis, and inhibits
      invasion through modulation of nuclear factor-kappaB activation pathway.
AB  - Recent reports have indicated that honokiol can induce apoptosis, suppress tumor
      growth, and inhibit angiogenesis. In this report, we found that honokiol
      potentiated the apoptosis induced by tumor necrosis factor (TNF) and
      chemotherapeutic agents, suppressed TNF-induced tumor cell invasion, and
      inhibited RANKL-induced osteoclastogenesis, all of which are known to require
      nuclear factor-kappaB (NF-kappaB) activation. Honokiol suppressed NF-kappaB
      activation induced by a variety of inflammatory stimuli, and this suppression was
      not cell type specific. Further studies showed that honokiol blocked TNF-induced
      phosphorylation, ubiquitination, and degradation of IkappaBalpha through the
      inhibition of activation of IkappaBalpha kinase and of Akt. This led to
      suppression of the phosphorylation and nuclear translocation of p65 and NF-kappaB
      dependent reporter gene expression. Magnolol, a honokiol isomer, was equally
      active. The expression of NF-kappaB-regulated gene products involved in
      antiapoptosis (IAP1, IAP2, Bcl-x(L), Bcl-2, cFLIP, TRAF1, and survivin),
      proliferation (cyclin D1, cyclooxygenase-2, and c-myc), invasion (matrix
      metalloproteinase-9 and intercellular adhesion molecule-1), and angiogenesis
      (vascular endothelial growth factor) were also down-regulated by honokiol.
      Honokiol also down-regulated NF-kappaB activation in in vivo mouse dorsal skin
      model. Thus, overall, our results indicate that NF-kappaB and NF-kappaB-regulated
      gene expression inhibited by honokiol enhances apoptosis and suppresses
      osteoclastogenesis and invasion.

PMID- 16966433
TI  - Nuclear factor Y drives basal transcription of the human TLX3, a gene
      overexpressed in T-cell acute lymphocytic leukemia.
AB  - Based on a knocked-out mouse model and a few expression studies, TLX3 is regarded
      as a homeobox gene crucial for the development of the autonomic nervous system.
      This gene can undergo rearrangements or deregulation, giving rise to T-cell acute
      lymphocytic leukemia. The present report is focused on the identification of
      elements and factors playing a role in the TLX3 physiologic expression regulation
      and therefore likely to be involved in cancer development. In particular, after
      identifying the transcription start points, we have made use of in vitro
      transfection assays to show that the 5'-untranslated region of the gene is
      necessary for the basal promoter activity in cell lines from different origin. By
      site-directed mutagenesis, two tandem CCAAT boxes have been localized as critical
      elements of this region. In vivo chromatin immunoprecipitation and
      electrophoretic mobility shift assays have indicated that nuclear factor Y (NFY)
      recognizes these sites in all the analyzed cell lines. The physiologic role of
      such an interaction has been confirmed by a dominant-negative version of the NFY
      transcription factor that has turned out to decrease both in vitro TLX3 promoter
      activity and endogenous amount of mRNA. Finally, a consistent in vivo TLX3
      expression impairment was also achieved after NFY mRNA knockdown. The full
      characterization of the TLX3 transcription regulation will ultimately provide
      crucial elements to define the involvement of this gene in T-cell acute
      lymphocytic leukemia development.

PMID- 16966434
TI  - ZNF652, a novel zinc finger protein, interacts with the putative breast tumor
      suppressor CBFA2T3 to repress transcription.
AB  - The transcriptional repressor CBFA2T3 is a putative breast tumor suppressor. To
      define the role of CBFA2T3, we used a segment of this protein as bait in a yeast
      two-hybrid screen and identified a novel uncharacterized protein, ZNF652. In
      general, primary tumors and cancer cell lines showed lower expression of ZNF652
      than normal tissues. Together with the location of this gene on the long arm of
      chromosome 17q, a region of frequent loss of heterozygosity in cancer, these
      results suggest a possible role of ZNF652 in tumorigenesis. In silico analysis of
      this protein revealed that it contains multiple classic zinc finger domains that
      are predicted to bind DNA. Coimmunoprecipitation assays showed that ZNF652
      strongly interacts with CBFA2T3 and this interaction occurs through the COOH
      terminal 109 amino acids of ZNF652. In contrast, there was a weak interaction of
      ZNF652 with CBFA2T1 and CBFA2T2, the other two members of this ETO family.
      Transcriptional reporter assays further confirmed the strength and selectivity of
      the ZNF652-CBFA2T3 interaction. The transcriptional repression of growth factor
      independent-1 (GFI-1), a previously characterized ETO effector zinc finger
      protein, was shown to be enhanced by CBFA2T1, but to a lesser extent by CBFA2T2
      and CBFA2T3. We therefore suggest that each of the various gene effector zinc
      finger proteins may specifically interact with one or more of the ETO proteins to
      generate a defined range of transcriptional repressor complexes.

PMID- 16966435
TI  - Endoplasmic reticulum vacuolization and valosin-containing protein relocalization
      result from simultaneous hsp90 inhibition by geldanamycin and proteasome
      inhibition by velcade.
AB  - Geldanamycin and Velcade, new anticancer drugs with novel mechanisms of action,
      are currently undergoing extensive clinical trials. Geldanamycin interrupts Hsp90
      chaperone activity and causes down-regulation of its many client proteins by the
      ubiquitin-proteasome pathway; Velcade is a specific proteasome inhibitor.
      Misfolded Hsp90 clients within the endoplasmic reticulum (ER) lumen are cleared
      by ER--associated protein degradation, a sequential process requiring valosin
      containing protein (VCP)-dependent retrotranslocation followed by ubiquitination
      and proteasomal proteolysis. Cotreatment of cells with geldanamycin and Velcade
      prevents destruction of destabilized, ubiquitinated Hsp90 client proteins,
      causing them to accumulate. Here, we report that misfolded protein accumulation
      within the ER resulting from geldanamycin and Velcade exposure overwhelms the
      ability of the VCP--centered machine to maintain the ER secretory pathway,
      causing the ER to distend into conspicuous vacuoles. Overexpression of dominant
      negative VCP or the "small VCP--interacting protein" exactly recapitulated the
      vacuolated phenotype provoked by the drugs, associating loss of VCP function with
      ER vacuolization. In cells transfected with a VCP--enhanced yellow fluorescent
      protein fluorescent construct, geldanamycin plus Velcade treatment redistributed
      VCP--enhanced yellow fluorescent protein from the cytoplasm and ER into
      perinuclear aggresomes. In further support of the view that compromise of VCP
      function is responsible for ER vacuolization, small interfering RNA interference
      of VCP expression induced ER vacuolization that was markedly increased by
      Velcade. VCP knockdown by small interfering RNA eventually deconstructed both the
      ER and Golgi and interdicted protein trafficking through the secretory pathway to
      the plasma membrane. Thus, simultaneous geldanamycin and Velcade treatment has
      far-reaching secondary cytotoxic consequences that likely contribute to the
      cytotoxic activity of this anticancer drug combination.

PMID- 16966438
TI  - Altered expression of beta-catenin, E-cadherin, cycloxygenase-2, and p53 protein
      by ovine intestinal adenocarcinoma cells.
AB  - Around 1.6% of sheep in New Zealand develop small-intestinal adenocarcinomas.
      These neoplasms typically develop widespread metastases. The common development
      of these neoplasms and their subsequent behavior suggests that sheep could be a
      useful animal model of human colonic cancer. However, for an animal model of
      human disease to be relevant, similar genetic mutations should be present.
      Genetic mutations within human colonic cancers frequently result in expression of
      cycloxygenase-2 (COX-2), loss of membranous expression of beta-catenin and E
      cadherin, and accumulation of p53 protein within the neoplastic cells.
      Immunohistochemistry was used to investigate the presence of these 4 proteins
      within 26 ovine intestinal adenocarcinomas. Loss of membranous beta-catenin
      reactivity was observed in 14 of 26 ovine intestinal adenocarcinomas (54%). The
      loss of membranous beta-catenin reactivity was accompanied by cytoplasmic and
      nuclear reactivity in 2 neoplasms. Loss of E-cadherin was observed within 8 of 26
      neoplasms (31%). Neoplastic cell expression of COX-2 was observed in 12 of 26
      neoplasms (46%), whereas cells within 3 of 26 neoplasms (11%) contained visible
      p53 protein. In conclusion, all 4 proteins that commonly have altered expression
      in human colonic cancers were also altered in a proportion of the ovine
      intestinal adenocarcinomas. These results provide additional evidence that sheep
      could be useful for the study of human colonic cancer.

PMID- 16966439
TI  - Prognostic significance of intratumoral microvessel density in canine soft-tissue
      sarcomas.
AB  - The prognosis of canine soft-tissue sarcomas (STS) has traditionally been based
      on histologic grading. We have recently demonstrated the prognostic value of
      cellular proliferation markers in canine STS. Another method of predicting the
      behavior of neoplasms is intratumoral microvessel density (IMD), which is a
      measure of tumor angiogenesis. The prognostic significance of IMD has been
      documented in many human neoplasms and in a limited number of canine and feline
      neoplasms. To evaluate the prognostic value of IMD in canine STS, we studied 57
      STS and compared IMD with histologic features, histologic grade, cellular
      proliferation, metastatic propensity, and survival. Using immunohistochemistry,
      the STS were labeled with anti-factor VIII-related antigen (FVIII-RA) and anti
      CD31 antibodies to determine 3 IMD parameters: mean microvessel density, high
      microvessel density, and microvessel area. Using FVIII-RA and CD31, increasing
      IMD was statistically associated with increasing histologic grade, necrosis
      scores, and mitotic scores. Higher FVIII-RA IMD values were significantly
      associated with higher median argyrophilic nucleolar organizing region (AgNOR)
      values (as previously investigated) and increased metastatic propensity.
      Fibrosarcomas appear to be the least vascularized of STS. There is no correlation
      between IMD and survival. Our results indicate that IMD is of prognostic value
      for histologic grade, histologic features, cellular proliferation (based on
      AgNOR), and metastatic propensity of canine STS, specifically when using FVIII-RA
      as the endothelial marker. Assessing histologic grading, cellular proliferation,
      and IMD of canine STS at the time of diagnosis could therefore provide better
      prognostic information for the veterinary clinician.

PMID- 16966437
TI  - Collectins and cationic antimicrobial peptides of the respiratory epithelia.
AB  - The respiratory epithelium is a primary site for the deposition of microorganisms
      that are acquired during inspiration. The innate immune system of the respiratory
      tract eliminates many of these potentially harmful agents preventing their
      colonization. Collectins and cationic antimicrobial peptides are antimicrobial
      components of the pulmonary innate immune system produced by respiratory
      epithelia, which have integral roles in host defense and inflammation in the
      lung. Synthesis and secretion of these molecules are regulated by the
      developmental stage, hormones, as well as many growth and immunoregulatory
      factors. The purpose of this review is to discuss antimicrobial innate immune
      elements within the respiratory tract of healthy and pneumonic lung with emphasis
      on hydrophilic surfactant proteins and beta-defensins.

PMID- 16966440
TI  - Canine hemophagocytic histiocytic sarcoma: a proliferative disorder of CD11d+
      macrophages.
AB  - Histiocytic disorders of dogs include histiocytoma, localized histiocytic sarcoma
      (HS), disseminated HS (malignant histocytosis), and the reactive histiocytoses:
      cutaneous and systemic. A common element to these diseases is proliferation of
      dendritic cells (DC) of either Langerhans cell (epithelial DC) or interstitial DC
      lineage. In this report, 17 dogs with hemophagocytic HS are described. Breeds
      affected included Bernese Mountain Dog (6), Golden Retriever (4), Rottweiler (3),
      Labrador Retriever (2), a mixed-breed dog, and a Schnauzer, which were from 2.5
      to 13 years old. The dogs presented with Coombs negative responsive anemia in
      16/17 dogs (94%), thrombocytopenia in 15/17 dogs (88%), hypoalbuminemia in 16/17
      dogs (94%), and hypocholesterolemia in 11/16 dogs (69%). All dogs died or were
      euthanized. The clinical course ranged from 2 to 32 weeks (mean 7.1 weeks).
      Diffuse splenomegaly with ill-defined masses was consistently present.
      Microscopic lesions were prevalent in spleen, liver, lung, and bone marrow.
      Metastasis occurred by insidious intravascular invasion with minimal mass
      formation. Histiocytes were markedly erythrophagocytic and accompanied by foci of
      extramedullary hemopoiesis. Cytologically, the histiocytes varied from well
      differentiated to atypical, with atypia more prevalent in spleen than bone
      marrow. These tumors arose from splenic red pulp and bone marrow macrophages,
      which expressed major histocompatibility complex class II and the beta2 integrin,
      CD11d. They had low and/or inconsistent expression of CD1 and CD11c, which are
      dominantly expressed by canine nonhemophagocytic HS of DC origin. Canine
      histiocytic proliferative diseases now encompass proliferation of all members of
      the myeloid histiocytic lineage: Langerhans cells, interstitial DC, and
      macrophages.

PMID- 16966441
TI  - Feline progressive histiocytosis.
AB  - Histiocytic proliferative diseases include reactive and neoplastic proliferations
      of dendritic cells (DC) or macrophages. Various forms of DC proliferations have
      been documented in humans and dogs; their etiology is largely unknown. With the
      exception of a few case reports, histiocytic proliferations have not been
      characterized in cats. This study summarizes clinical, morphologic, and
      immunophenotypic features of a feline progressive histiocytosis (FPH) in 30 cats.
      There was no breed or age predilection. Females were more often affected than
      males. Solitary or multiple nonpruritic firm papules, nodules, and plaques had a
      predilection for feet, legs, and face. Lesions consisted of poorly circumscribed
      epitheliotropic (13/30) and nonepitheliotropic (17/30) histiocytic infiltrates of
      the superficial and deep dermis, with variable extension into the subcutis. The
      histiocytic population was relatively monomorphous early in the clinical course.
      With disease progression, cellular pleomorphism was more frequently encountered.
      Histiocytes expressed CD1a, CD1c, CD18, and major histocompatibility complex
      class II molecules. This immunophenotype suggests a DC origin of these lesions.
      Coexpression of E-cadherin, a feature of cutaneous Langerhans cells, was only
      observed in 3 cats. FPH followed a progressive clinical course; the lesions,
      however, were limited to the skin for an extended period of time. Terminal
      involvement of internal organs was documented in 7 cases. Treatment with
      chemotherapeutics or immunosuppressive and immunomodulatory drugs was not
      successful. The etiology of FPH remains unknown. FPH is best considered an
      initially indolent cutaneous neoplasm, which is mostly slowly progressive and may
      spread beyond the skin in the terminal stage.

PMID- 16966442
TI  - Cyclooxygenase-2 expression in normal and neoplastic canine mammary cell lines.
AB  - Mammary cancer is the most common cancer in female dogs. Induction of
      cyclooxygenase-2 (COX-2), a key enzyme in prostaglandins (PGs) biosynthesis, has
      been demonstrated in various cancers in humans and dogs, including mammary
      cancer. The objective of this study was to investigate the expression and
      regulation of COX-2 in canine mammary epithelial cells. Cell lines derived from
      normal and neoplastic canine mammary glands were cultured in the absence or
      presence of phorbol 12-myristate 13-acetate (PMA), and immunoblots,
      immunocytochemistry, radioimmunoassays, and a cell proliferation assay were used
      to study COX-2 expression and PGs production. Results showed that the neoplastic
      cell line CMT12 constitutively overexpressed COX-2 protein whereas other mammary
      cell lines expressed low to undetectable basal levels of COX-2 protein. Basal
      PGE(2) production was significantly higher (P < .05) in CMT12 compared to other
      cell lines. Levels of COX-2 protein in CMT12 decreased in a time-dependent manner
      with serum starvation, and PMA stimulation induced a strong time-dependent
      increase in COX-2 protein. Treatment of CMT12 cells with NS-398 (a specific COX-2
      inhibitor) significantly blocked PGE(2) synthesis and reduced cell proliferation
      (P < .05). These results indicate that some neoplastic canine mammary cell lines
      constitutively overexpress COX-2, and that COX-2 inhibition decreases PGE(2)
      production and cell proliferation, supporting a role for COX-2 and PGs in canine
      mammary oncogenesis.

PMID- 16966443
TI  - Mammary mucinous carcinoma in the cat.
AB  - Mucinous carcinoma of the mammary gland is a rare tumor characterized by
      excessive mucin production. In human and canine pathology, the diagnosis of
      mucinous carcinoma is based on the demonstration of an epithelial phenotype of
      mucus-producing cells and periodic acid-Schiff (PAS)-diastase positivity of the
      mucin. The histologic and immunohistologic characteristics of feline mucinous
      mammary carcinoma were examined. Of 656 cases of feline mammary neoplasms and
      dysplasias, 3.2% were found to be mucin-producing tumors. Cytokeratin 19 (16
      cases positive, 4 heterogenous, and 1 negative) and vimentin (15 cases positive,
      2 heterogenous, and 4 negative) expression were examined, and the mucin produced
      was alcian blue positive. PAS-diastase staining was variable (38.1%). Based on
      these findings, mucinous mammary carcinoma in the cat varies significantly from
      the human and canine varieties and alcian blue is the prominent stain in the
      diagnosis of feline mucinous carcinoma.

PMID- 16966444
TI  - Transitional cell carcinoma in fishing cats (Prionailurus viverrinus): pathology
      and expression of cyclooxygenase-1, -2, and p53.
AB  - A high prevalence of urinary bladder transitional-cell carcinoma (TCC) has been
      noted in captive fishing cats (Prionailurus viverrinus). Of the 91 adult deaths
      between 1995 and 2004, 12 (13%) were attributed to TCC. To help elucidate
      mechanisms of carcinogenesis, archival sections of urinary bladder from 14
      fishing cats were examined histologically and immunohistochemically for p53,
      cyclooxygenase (COX)-1, and COX-2 expression. Ten cats had TCC, and 4 were
      unaffected. The average age at death was 10.8 years in affected individuals and
      10.5 years in unaffected individuals. There was no sex predilection. Fishing cat
      TCCs were characterized histologically as papillary and infiltrating (n = 6),
      nonpapillary and infiltrating (n = 3), or carcinoma in situ (n = 1). Glandular
      and squamous metaplasia, necrosis, and lymphatic invasion were prominent
      histologic features. Two individuals had documented metastasis. p53 nuclear
      immunolabeling was detected in 4/10 (40%) TCCs. In two cases, immunolabeling was
      limited to less than 10% of the neoplastic cellular population and was comparable
      to staining of normal fishing cat bladder. Therefore, p53 gene mutation did not
      appear to be an essential component of TCC carcinogenesis in examined fishing
      cats. COX-1 immunohistochemistry was negative in all cases. All TCCs had some
      degree of COX-2 cytoplasmic immunolabeling, which was exclusively within the
      invasive portions of the neoplasms. Papillary portions were uniformly negative.
      COX-2 overexpression was a prominent feature in the majority of the examined
      fishing cat TCCs, suggesting that COX-2-mediated mechanisms of carcinogenesis are
      important in this species and that COX-inhibiting drugs may be of therapeutic
      benefit.

PMID- 16966445
TI  - Eosinophilic crystalline pneumonia as a major cause of death in 129S4/SvJae mice.
AB  - Eosinophilic crystalline pneumonia is an idiopathic disease that occurs in many
      strains and stocks of mice, more commonly in strains on a C57BL/6 background. The
      disease occurs sporadically in most strains of mice and varies from mild and
      subclinical to severe and fulminating, sometimes resulting in respiratory
      distress and death. In this study, 94 aged male and female 129S4/SvJae mice were
      evaluated for eosinophilic crystalline pneumonia lesions. There was an 87%
      incidence, with females overrepresented. Histologically, there were multifocal to
      coalescing inflammatory infiltrates composed of numerous large eosinophilic
      macrophages and multinucleate cells admixed with eosinophils, neutrophils,
      lymphocytes, and plasma cells within alveolar and bronchiolar spaces, associated
      with refractile, brightly eosinophilic, angular crystals. Alveolar macrophages
      and multinucleate cells contained fine needlelike to rectangular intracytoplasmic
      crystalline material. Similar crystals were often free within alveoli and
      conducting airways, often associated with mucous metaplasia of bronchiolar
      epithelium. This disease may occur spontaneously or in concert with other
      pulmonary lesions, such as pulmonary adenomas, lymphoproliferative disease,
      allergic pulmonary disease, and parasitic or fungal infections. The
      characteristic crystals morphologically resemble Charcot-Leyden crystals, which
      represent eosinophil breakdown products in humans with eosinophil-related
      disease. However, crystals in eosinophilic crystalline pneumonia are composed
      predominantly of Ym1 protein, a chitinase-like protein associated with neutrophil
      granule products and secreted by activated macrophages. The function of Ym1
      protein is not fully understood but is believed to be involved in host immune
      defense, eosinophil recruitment, and cell-cell and cell-matrix interactions
      consistent with tissue repair. The mechanism of induction of eosinophilic
      crystalline pneumonia with Ym1 crystal formation is unknown.

PMID- 16966446
TI  - Monocytic/macrophagic pneumonitis after intrabronchial deposition of vascular
      endothelial growth factor in neonatal lambs.
AB  - Preterm and young neonates are prone to inadequate surfactant production and are
      susceptible to respiratory distress syndrome characterized by alveolar damage and
      hyaline-membrane formation. Glucocorticoid therapy is commonly used in preterm
      and young infants to enhance lung maturation and surfactant synthesis. Recently,
      vascular endothelial growth factor (VEGF) was suggested to be a novel therapeutic
      agent for lung maturation that lacked adverse effects in mice. The purpose of
      this study was to assess the safety of incremental concentration (0.0005, 0.005,
      and 0.05 mg/ml) and duration (16, 24, and 32 hours) of recombinant human VEGF
      after bronchoscopic instillation (10 ml) in neonatal lambs. High-dose VEGF caused
      locally extensive plum-red consolidation that was microscopically characterized
      by interstitial and alveolar infiltrates of cells that were morphologically and
      phenotypically (CD68+) consistent with monocytes/macrophages. T cells (CD3+) and
      B cells (CD79+) were located primarily in bronchus/bronchiole-associated lymphoid
      tissue and were not consistently altered by treatment with VEGF. The dose of VEGF
      had significant effects on both gross lesions (P < .0047) and microscopic
      monocyte/macrophage recruitment scores (P < .0001). Thus, the VEGF dose instilled
      into the lung greatly influenced cellular recruitment and lesion development. The
      post-dosing interval of VEGF in this study had minor impact (no statistical
      significance) on cellular recruitment. This study showed that airway deposition
      of VEGF in the neonatal lamb induces monocyte/macrophage recruitment to the lung
      and high doses can cause severe lesions. The cellular recruitment suggests
      further research is needed to define dosages that are efficacious in enhancing
      lung maturation while minimizing potential adverse effects.

PMID- 16966447
TI  - Neurohistologic and ultrastructural lesions in cattle experimentally intoxicated
      with the plant Prosopis juliflora.
AB  - Intoxication by pods of Prosopis juliflora (mesquite beans) causes an impairment
      of cranial nerve function in cattle and goats. In goats, vacuolation of neurons
      in the trigeminal motor nuclei has been reported. To study the lesions in cattle
      caused by consumption of P. juliflora pods and dry ground pods, eight 6- to 12
      month-old male cattle were divided into 4 groups: group 1 was fed a ration
      containing 50% of pods; groups 2 and 3 received a ration containing 50 and 75% of
      dry ground pods, respectively; group 4 was the control. After 200 days, all
      cattle were killed and sampled for histologic evaluation. Samples of the
      trigeminal motor nucleus were examined by electron microscopy. All cattle from
      groups 1, 2, and 3 showed clinical signs resulting from impaired function of
      cranial nerves V, IX, X, and XII, starting 45-75 days after consumption of the
      plant. The main histologic lesions were vacuolation and loss of neurons in
      trigeminal motor nuclei and other motor cranial nerve nuclei with Wallerian-like
      degeneration in the cranial nerves. Mild denervation atrophy was observed in the
      masseter and other masticatory muscles. On electron microscopy, neurons of the
      trigeminal nuclei had markedly swollen mitochondria, with the mitochondrial
      cristae displaced peripherally, disoriented and disintegrating. Intoxication by
      P. juliflora seems to have a novel pathogenesis, characterized by a selective,
      primary, chronic, and progressive injury to mitochondria of neurons of the
      trigeminal and other cranial nerve nuclei. Cranial nerve degeneration and
      denervation atrophy of the muscles occurs as a consequence of the neuronal
      lesion.

PMID- 16966448
TI  - Chlamydia-related abortions in cattle from Graubunden, Switzerland.
AB  - In 2001, the first case of bovine chlamydial abortion was reported in canton
      Graubunden, Switzerland. In this region, Chlamydophila (Cp.) abortus is endemic
      in small ruminants. Hence, we aimed to investigate the incidence of chlamydia
      related abortions in cattle from Graubunden. During breeding seasons of 2003
      2004, formalin-fixed and paraffin-embedded placenta specimens (n = 235) from late
      term abortions in cattle were analyzed by histopathology, immunohistochemistry
      with a Chlamydiaceae-specific monoclonal antibody against chlamydial
      lipopolysaccharide (LPS), and 2 different polymerase chain reaction (PCR) methods
      (16 S ribosomal ribonucleic acid [rRNA] PCR, intergenic spacer [IGS-S] PCR),
      followed by PCR product sequencing. In 149 of 235 cases (63.4%), histopathologic
      lesions such as purulent and/or necrotizing placentitis were observed. Chlamydial
      antigen was clearly demonstrated in immunohistochemistry in only 1 of 235 cases
      (0.4%). Cp. abortus or Cp. psittaci was found in 12 of 235 (5.1%) and 10 of 235
      cases (4.2%) by 16 S rRNA PCR and IGS-S PCR, respectively. However, we detected,
      by 16 S rRNA PCR, 43 of 235 cases (18.3%) to be positive for chlamydia-like
      organisms. In contrast to the situation in small ruminants in the canton
      Graubunden, bovine abortion from Cp. abortus seems not to play an important role.
      Nevertheless, zoonotic potential should be taken into account when handling
      abortion material from cattle. The significance of chlamydia-like isolates other
      than Waddlia chondrophila remains an open question in abortion and needs further
      investigation.

PMID- 16966449
TI  - Coexpression of NRAMP1, iNOS, and nitrotyrosine in bovine tuberculosis.
AB  - In murine models the inducible nitric oxide synthase (iNOS) and the natural
      resistance associated macrophage protein (NRAMP1) play major roles in host
      defense against mycobacteria. iNOS regulates nitric oxide (NO) production, which
      is noxious for ingested mycobacteria, and NRAMP1 displays pleiotropic
      antimicrobial effects, including upregulation of iNOS expression. Little is known
      about the role of these molecules in bovine tuberculosis (TB). In this work we
      demonstrate by Western blot a high expression of NRAMP1 in peripheral blood
      mononuclear cells (PBMCs), alveolar macrophages (obtained by bronchioalveolar
      lavage), and lymph node granulomas from 8 Holstein-Freisian cattle with autopsy
      proven bovine TB. Immunohistochemistry revealed the abundant expression of NRAMP1
      and iNOS in lymph node and lung granulomas. Immunoreactivity was abundant in the
      cytoplasm of many epithelioid macrophages and multinucleated giant cells of the
      Langhans type. A striking accumulation of nitrotyrosine (NT), an indicator of
      iNOS activity and local NO production, was observed in granuloma cells,
      particularly in multinucleated Langhans cells. This study shows that the
      expression of NRAMP1 and iNOS is costimulated in granulomas, which are protective
      T-cell reactions against mycobacteria.

PMID- 16966450
TI  - Potentiation of porcine circovirus 2-induced postweaning multisystemic wasting
      syndrome by porcine parvovirus is associated with excessive production of tumor
      necrosis factor-alpha.
AB  - This study investigated the potentiation of porcine circovirus 2 (PCV2)-induced
      postweaning multisystemic wasting syndrome by porcine parvovirus (PPV) and found
      it was associated with excessive production of tumor necrosis factor-alpha (TNF
      alpha). Colostrum-deprived conventional pigs were inoculated intranasally with
      PCV2 or PPV alone or in combination (PCV2 and PPV). In vitro assay of TNF-alpha,
      obtained from alveolar macrophages coinfected with PCV2 and PPV, showed a
      significant increase in TNF-alpha compared to single infection of macrophages
      with either PCV2 or PPV alone (P < 0.05). All pigs inoculated with PCV2 and PPV
      developed severe postweaning wasting syndrome, whereas clinical signs (e.g.,
      weight loss) were present but perhaps less severe in either PCV2- or PPV
      inoculated pigs. Compared to the pigs inoculated with PCV2 or PPV alone, pigs
      inoculated dually with PCV2 and PPV showed significantly (P < 0.05) increased
      levels of TNF-alpha. Levels of TNF-alpha in the sera were reversely correlated
      with the body weight in pigs experimentally infected with dual inoculation of
      PCV2 and PPV (r(s) = -0.92, P < 0.001). These data suggest that a potentiation of
      PPV in PCV2-induced PMWS is associated with the excessive production of TNF
      alpha.

PMID- 16966451
TI  - Defective gamma-glutamyl carboxylase activity and bleeding in Rambouillet sheep.
AB  - A flock of Rambouillet sheep was examined because of increased lamb mortality
      caused by ineffective hemostasis at parturition. Neonatal-affected lambs
      presented with inadequate hemostasis at the umbilicus, pale mucus membranes, and
      markedly prolonged activated clotting time. Affected lambs had consistently
      prolonged 1-stage prothrombin times and activated partial thromboplastin times
      that supported a defect in the common pathway or defects in both the intrinsic
      and extrinsic pathway of the coagulation cascade. Decreased activity of vitamin K
      dependent procoagulant factors II, VII, IX, and X in male and female lambs
      suggested either a defect of the hepatic enzyme gamma-glutamyl carboxylase, or
      vitamin K(1) 2,3 epoxide reductase. Affected lamb hepatic gamma-glutamyl
      carboxylase activity was markedly decreased compared with that of age- and sex
      matched control lambs, while vitamin K(1) 2,3 epoxide reductase and glucose-6
      phosphatase activities were similar between an affected and normal lamb.
      Subcutaneous vitamin K(1) supplementation did not increase vitamin K-dependent
      procoagulant factor activities in 3 lambs administered vitamin K(1) daily. These
      data confirm defective gamma-glutamyl carboxylase activity as the cause of
      impaired coagulation of sheep in this flock. This flock represents the only
      viable animal model of hereditarily defective gamma-glutamyl carboxylase
      activity.

PMID- 16966452
TI  - Abnormal prion accumulation associated with retinal pathology in experimentally
      inoculated scrapie-affected sheep.
AB  - The purpose of this study was to characterize the patterns of PrP(Sc)
      immunoreactivity in the retinae of scrapie-affected sheep and to determine the
      extent of retinal pathology as indicated by glial fibrillary acidic protein
      immunoreactivity (GFAP-IR) of Muller glia. Sections from the retina of 13
      experimentally inoculated scrapie-affected and 2 negative control sheep were
      examined with immunohistochemical staining for PrP(Sc), GFAP, and PrP(Sc)/GFAP
      double staining. GFAP-IR of Muller glia is suggestive of retinal pathology in the
      absence of morphologic abnormality detected by light microscopy. Sheep with the
      least amount of PrP(Sc) in the retina have multifocal punctate aggregates of
      prion staining in the outer half of the inner plexiform layer and rarely in the
      outer plexiform layer. In these retinae, GFAP-IR is not localized with prion
      accumulation, but rather is present in moderate numbers of Muller glia throughout
      the sections of retina examined. The majority of sheep with retinal accumulation
      of PrP(Sc) have intense, diffuse PrP(Sc) staining in both plexiform layers, with
      immunoreactivity in the cytoplasm of multiple ganglion cells and lesser amounts
      in the optic fiber layer and between nuclei in nuclear layers. This intense
      PrP(Sc) immunoreactivity is associated with diffuse, intense GFAP-IR that extends
      from the inner limiting membrane to the outer limiting membrane. This is the
      first report of a prion disease in a natural host that describes the accumulation
      of PrP(Sc) in retina associated with retinal pathology in the absence of overt
      morphologic changes indicative of retinal degeneration.

PMID- 16966453
TI  - Age-related and non-age-related changes in 100 surveyed horse brains.
AB  - Brains from 100 horses, aged 2-25 years, were systematically examined by
      histopathology at 46 different neuroanatomical sites. The horses were sourced
      from a slaughterhouse (group A, n = 57), from a kennel that collected dead
      animals, and from 2 diagnostic laboratories (group B, n = 43). All horses from
      group A and 26 horses from group B were examined by a veterinarian in the period
      before death. None of the horses were known to exhibit clinical signs suggestive
      of neurologic disease. Among the main changes identified were vacuolation in the
      neuropil (n = 73), neurons (n = 32), white matter (n = 31), and focal
      perivascular lymphoid cell infiltrates (n = 35). Spheroids were frequently seen
      (n = 91), and 10 horses each had more than 10 spheroids in the cuneate or gracile
      nucleus. Statistically significant age-related changes noted included
      intraneuronal (n = 97) and glial or extracellular lipofuscin deposition (n = 41),
      hemosiderin deposition around blood vessels (n = 60), and calcium depositions (n
      = 24). One horse had low-grade nonsuppurative meningoencephalitis; Alzheimer type
      II cells were detected in the brains of 2 horses. Hyalinized vessel walls in the
      cerebellum were observed in 1 horse. It was concluded that some histopathologic
      changes are a frequent feature in equine brains, which has implications for the
      pathologists involved in equine neurology and disease surveillance.

PMID- 16966454
TI  - Nasal oncocytoma in a domestic shorthair cat.
AB  - An oncocytoma was diagnosed in the nasal cavity of a 12-year-old Domestic
      Shorthair cat who presented with periocular swelling and sneezing. Histologic
      examination from biopsy material revealed monomorphic sheets, anastomosing cords,
      tubules, and acini composed of large polygonal to oval cells that contained
      abundant finely granular eosinophilic cytoplasm. No vascular or lymphatic
      invasions were noted. Histochemical stains revealed positive staining of tumor
      cells with periodic acid-Schiff (PAS) (before and after diastase digestion) and
      phosphotungstic acid-hematoxylin. Immunohistochemical evaluation of the tumor
      cells demonstrated positive staining for cytokeratin and negative staining for
      vimentin, desmin, S-100, glial fibrillar acidic protein, and neuronal specific
      enolase. Ultrastructurally, the tumor cells contained large numbers of
      mitochondria within their cytoplasm, which confirmed a diagnosis of oncocytoma.

PMID- 16966455
TI  - Immunohistochemical identification and pathologic findings in natural cases of
      equine abortion caused by leptospiral infection.
AB  - The aim of this study was to examine the utility of immunohistochemistry (IHC) in
      the diagnosis of leptospiral equine abortion and to compare IHC to silver
      staining and serology of the aborted mares. Ninety-six fetuses from 57 farms were
      examined using all 3 diagnostic techniques, revealing evidence of leptospiral
      infection in 3 fetuses (3.1%) from 3 (5.3%) different farms. A new finding in 1
      of these confirmed cases of leptospiral abortion was the presence of macroscopic
      pinpoint grayish-white nodules that had a histologic correlate of hepatic
      necrosis; other histologic findings were consistent with those previously
      reported. IHC performed using 2 different leptospiral antisera (multivalent whole
      cell rabbit antiserum and rabbit antiserum against the major outer membrane
      protein LipL32) yielded similar results. IHC was more sensitive (19/21 [90.5%]
      tissue samples) than silver staining (8/21 [38.1%] tissue samples), and more
      specific than serology performed using the microscopic agglutination test. The
      primary advantage of IHC over silver staining was the ability of IHC to identify
      leptospiral antigen not only as morphologically intact spiral forms.

PMID- 16966456
TI  - A case of interface perianal dermatitis in a dog: is this an unusual
      manifestation of lupus erythematosus?
AB  - Discoid lupus erythematosus (DLE) is a well-known autoimmune disorder described
      in dogs and humans. In dogs, DLE is considered the second most common immune
      mediated dermatitis and is usually localized to the nasal planum. DLE does not
      evolve to generalized disease, however lesions may spread to the bridge of the
      nose and less commonly may extend to periocular region, pinnae, distal limbs, and
      mucocutaneous junctions (lips, oral cavity, and genital region). A 4-year-old
      male Bavarian Mountain Scenthound developed a chronic, erosive, cutaneous lesion
      located exclusively in the perianal region without facial skin involvement.
      Clinical signs included erythema, depigmentation, severe alopecia, crusting, and
      ulceration. Histologically, the hallmarks of the changes were an interface
      dermatitis consisting of plasma cells, lymphocytes, neutrophils, and macrophages,
      hydropic degeneration of basal cells, few apoptotic cells in the basal layer,
      pigmentary incontinence, and a focal thickening of the basement membrane, which
      was characterized by linear deposition of IgG. Despite the unusual localization
      the lesion was diagnosed as DLE based on the characteristic histologic and
      immunohistologic features. Following diagnosis, corticosteroid therapy resulted
      in a complete resolution of perianal lesions.

PMID- 16966457
TI  - Clostridium piliforme infection in two farm-raised white-tailed deer fawns
      (Odocoileus virginianus) and association with copper toxicosis.
AB  - Necropsy of 2 white-tailed deer fawns who died acutely revealed diarrhea and
      melena in case No. 1 and no gross changes in case No. 2. Histologically, the
      livers of both deer displayed multifocal coagulative necrosis, with infiltrations
      of neutrophils, macrophages, and lymphocytes. By Warthin-Starry staining, bundles
      of filamentous bacteria were identified within hepatocytes at the periphery of
      the necrotic foci in case No. 1. There was multifocal myocardiocyte necrosis in
      case No. 1 and multifocal lymphoid necrosis of the Peyer's patches in case No. 2.
      Clostridium piliforme 16S ribosomal ribonucleic acid gene was detected in both
      livers by polymerase chain reaction (PCR) with C. piliforme-specific primers. The
      liver copper levels in both cases were normal to slightly elevated. The kidney
      copper level in case No. 2 was elevated. This represents the first published
      cases of Tyzzer's disease in deer, a novel use of PCR for the diagnosis of C.
      piliforme infection, and a possible association between copper toxicosis and
      Tyzzer's disease.

PMID- 16966458
TI  - Fatal herpesvirus encephalitis in a reticulated giraffe (Giraffa camelopardalis
      reticulata).
AB  - Fatal meningoencephalitis caused by equine herpesvirus-1 (EHV-1) was diagnosed in
      a reticulated giraffe (Giraffa camelopardalis reticulate). The giraffe died
      following a history of stumbling, incoordination, and abdominal pain. Gross
      examination of the brain revealed asymmetric edema and red-brown discoloration,
      predominantly within the telencephalon. Microscopically, there was perivascular
      lymphohistiocytic cuffing, multifocal gliosis, and neuronal necrosis in the
      cerebrum. Necrotic neurons contained acidophilic intranuclear inclusions. EHV-1
      was isolated from the brain of the giraffe, and polymerase chain reaction was
      positive on sections of the brain. Immunohistochemistry using an EHV-1-specific
      antibody identified positive staining in neurons, astrocytes, and endothelial
      cells. The giraffe had been housed with a group of zebras that were serologically
      positive for EHV-1 and suspected as the source of infection. This raises concerns
      for cross-species transmission of EHV-1 when housing equids together with other
      species in zoologic collections.

PMID- 16966459
TI  - Immunohistochemical detection of Ym1/Ym2 chitinase-like lectins associated with
      hyalinosis and polypoid adenomas of the transitional epithelium in a mouse with
      acute myeloid leukemia.
AB  - An 8-month-old PML/RARalpha knock-in female mouse developed a promyelocytic-like
      myeloid leukemia with an expected latency. At necropsy, besides the typical
      findings associated with myeloid leukemia, a severe unilateral hydronephrosis was
      observed. By histopathologic examination, 2 polypoid adenomas arising from the
      transitional epithelium of the renal pelvis and ureter were detected. The
      epithelial cells of the polypoid adenomas showed accumulation of hyaline
      eosinophilic material within the cytoplasm. Large amounts of extracellular
      eosinophilic crystals were also associated with the transitional cell adenomas.
      Immunohistochemical analysis revealed that the eosinophilic intracytoplasmic
      material and the extracellular eosinophilic crystals were composed of Ym
      proteins. A unilateral hyaline droplet tubular nephropathy was associated with
      the myeloid leukemia. Expression of Ym proteins characterized both the neoplastic
      myeloid infiltrates and the tubular hyaline droplets. In the present PML/RARalpha
      knock-in female mouse, the accumulation of Ym proteins associated with the
      myeloid leukemia and with the polypoid adenomas of the transitional epithelium
      underlies 2 distinct pathogenetic mechanisms.

PMID- 16966460
TI  - Natural occurrence of amyloid-Abeta deposits in the brain of young common
      marmosets (Callithrix jacchus): a morphological and immunohistochemical
      evaluation.
AB  - The spontaneous incidence and distribution of beta-amyloid (Abeta) peptide and
      argyrophilic deposits were extensively investigated in the common marmoset
      (Callithrix jacchus). In 12 young marmosets, up to 67 coronal step sections were
      evaluated in the brain. One brain hemisphere was stained by a silver method and
      also immunohistochemically with a primary antibody directed against Abeta.
      Argyrophilic deposits were observed in 4 (33%) of 12 animals with silver stain,
      and Abeta was seen in 4 (33%) of 12 animals with anti-4G8 antibody. The overall
      incidence was 6 (50%) of 12 affected animals. These results show that the young
      marmoset brain displays Abeta deposits at a low incidence and that
      immunohistochemistry is more suitable than silver staining to reveal rare amyloid
      plaques. These findings also provide evidence for the early onset of amyloid
      deposits in marmoset brain.

PMID- 16966461
TI  - Avian riboflavin deficiency: an acquired tomaculous neuropathy.
AB  - The finding of tomacula, focal areas of sausage-shaped hypermyelination in
      peripheral nerves, is reported for the first time in avian riboflavin deficiency.
      Day-old, meat-type chickens were fed a riboflavin-deficient diet (1.8 mg/kg) and
      were killed on postnatal days 6, 11, 16, and 21, while control chickens were fed
      a conventional diet containing 5.0 mg/kg riboflavin. Tomacula were found in
      sciatic and brachial nerves from day 11 onward, became more frequent and
      prominent with increasing time, and preceded the onset of segmental
      demyelination.

PMID- 16966462
TI  - Primary cerebral hemangiosarcoma in a 6-week-old dog.
AB  - A primary cerebral hemangiosarcoma was identified in a 6-week-old, female, cross
      breed dog. Grossly, the tumor mass was poorly demarcated from the adjacent
      neuropil, hemorrhagic, and caused effacement of the right dorsolateral cerebral
      hemisphere. Microscopically, the tumor was composed of an infiltrative mass of
      small vascular channels lined by neoplastic endothelial cells that stained
      variably with factor VIII-related antigen and negatively with glial fibrillary
      acidic protein. This is the first description of a primary intracranial
      hemangiosarcoma in an immature dog.

PMID- 16966463
TI  - Placental tumor from an East African bongo (Eurycerus isaaci) fetus.
AB  - This case report describes a placental tumor from a stillborn East African bongo
      fetus. On gross examination, the tumor was reminiscent of a chorangioma; however,
      based on histomorphology, histochemical and immunophenotypic characterization,
      comparison to 21 human cases of chorangioma, and embryogenesis, this tumor is
      hypothesized to be a placental stem cell tumor. Histologically, the tumor had 2,
      often commingled, morphologies with one area having dense cellularity and scant
      vascularity and a second area having scant cellularity and prominent vascularity.
      Pleomorphic mesenchymal cells were arranged in intersecting fascicles, often
      whorled around, or were contiguous with vascular channels and had features of
      skeletal muscle, smooth muscle, pericyte, endothelial, fibrous, and
      undifferentiated mesenchymal cells. Phosphotungstic acid-hematoxylin outlined
      cross-striations in some cells. Cells variably were immunoreactive for vimentin,
      CD31, von Willebrand factor VIII, desmin, muscle specific actin, alpha-smooth
      muscle actin, and skeletal myosin and negative for cytokeratin antigens. The
      relationship of this tumor to the presence of fetal musculoskeletal and omental
      anomalies is discussed.

PMID- 16966464
TI  - Chromosome instability in a calf with amelia of thoracic limbs.
AB  - We report here on a case of a Holstein-Friesian male calf with the congenital
      total absence of thoracic limbs (amelia). Cytogenetic study showed a high rate of
      chromosome instability, represented by chromosome or chromatid breaks and gaps in
      46% of the analyzed metaphase spreads. Moreover, 12% of the spreads appeared to
      be polypolid. The number of micronuclei also was significantly higher when
      compared to control animals. This paper discusses the association between
      chromosome instability and limb malformation.

PMID- 16966465
TI  - Liposarcoma in the nasal cavity of a cow.
AB  - Liposarcomas are rare neoplasms in domestic animals, but have been reported to
      occur in many species. In humans, liposarcoma is one of the most common malignant
      mesenchymal tumors. Classification of liposarcomas in humans has been well
      established and categorization by type can be of prognostic value; no such unique
      classification scheme has been established for liposarcomas in animals.
      Liposarcoma of the head and neck in humans are uncommon, and are rarely reported
      in the nasal cavity, sinuses, and nasopharynx. To our knowledge, a liposarcoma
      has never been reported in the nasal cavity of a domestic animal. In this report
      we describe a liposarcoma that developed in the nasal cavity of a cow, with local
      invasion into the oral cavity.

PMID- 16966466
TI  - A cerebral granular cell tumor in a cat.
AB  - A cerebral granular cell tumor is described in a 6-year-old, short-haired, female
      cat. The tumor was observed above the corpus callosum and completely infiltrating
      the third ventricle. Histologic examination revealed that the tumor was
      characterized by large cells containing densely packed intracytoplasmic granules
      and expressed psammoma body-like patterns and cholesterinic degeneration.
      Immunohistochemical analysis revealed granular neoplastic cells that were
      diffusely and strongly vimentin-positive, while they did not express
      cytokeratins, lysozyme, and synaptophysin. Based on morphologic and
      immunohistochemical findings, the tumor under study was considered to be of
      meningeal origin arising directly from the meninges or from meningeal elements
      scattered in the tela choroidea of the third ventricle roof.

PMID- 16966469
TI  - Anti-influenza prodrug oseltamivir is activated by carboxylesterase human
      carboxylesterase 1, and the activation is inhibited by antiplatelet agent
      clopidogrel.
AB  - Oseltamivir is the main medicine recommended by the World Health Organization in
      anticipation of next influenza pandemic. This anti-influenza viral agent is an
      ester prodrug, and the antiviral activity is achieved by its hydrolytic
      metabolite: oseltamivir carboxylate. In this study, we report that the hydrolytic
      activation is catalyzed by carboxylesterase human carboxylesterase (HCE) 1. Liver
      microsomes rapidly hydrolyzed oseltamivir, but no hydrolysis was detected with
      intestinal microsomes or plasma. The overall rate of the hydrolysis varied among
      individual liver samples and was correlated well with the level of HCE1.
      Recombinant HCE1 but not HCE2 hydrolyzed this prodrug and produced similar
      kinetic parameters as the liver microsomes. Several HCE1 natural variants
      differed from the wild-type enzyme on the hydrolysis of oseltamivir. In the
      presence of antiplatelet agent clopidogrel, the hydrolysis of oseltamivir was
      inhibited by as much as 90% when the equal concentration was assayed. Given the
      fact that hydrolysis of oseltamivir is required for its therapeutic activity,
      concurrent use of both drugs would inhibit the activation of oseltamivir, thus
      making this antiviral agent therapeutically inactive. This is epidemiologically
      of significance because people who receive oseltamivir and clopidogrel
      simultaneously may maintain susceptibility to influenza infection or a source of
      spreading influenza virus if already infected.

PMID- 16966470
TI  - Time-dependent cognitive deficits associated with first and second generation
      antipsychotics: cholinergic dysregulation as a potential mechanism.
AB  - Although cognitive dysfunction is considered one of the more debilitating
      symptoms of schizophrenia, there is a fundamental gap in our knowledge of how the
      primary pharmacologic treatments of this disease, first- and second-generation
      antipsychotics (FGAs and SGAs, respectively), affect cognition, particularly over
      extended periods of time. Moreover, it has been known for decades that chronic
      treatment with FGAs can lead to imbalances in cholinergic function in the
      striatum that result in movement disorders; however, there is a growing body of
      evidence to suggest that both FGAs and SGAs can lead to cholinergic alterations
      in brain areas more traditionally considered as memory-related, such as cortical
      and hippocampal regions. Data from our laboratories in rodents indicate that some
      SGAs (if administered for sufficient periods of time) can be associated with
      impairments in memory-related task performance as well as alterations in the
      cholinergic enzyme choline acetyltransferase, the vesicular acetylcholine
      transporter, and nicotinic (alpha(7)) and muscarinic (M(2)) acetylcholine
      receptors. Given the well documented importance of central cholinergic function
      to information processing and cognitive function, it is important that the
      mechanisms for such chronic antipsychotic effects be identified. In this review,
      two potential mechanisms for long-term antipsychotic-related cholinergic
      alterations in the central nervous system are discussed: 1) antipsychotic
      antagonist activity at dopaminergic-D(2) receptors on cholinergic neurons and 2)
      antipsychotic effects on neurotrophins that support cholinergic neurons, such as
      nerve growth factor and brain derived growth factor. Novel strategies to optimize
      the therapeutics of schizophrenia and maintain cognitive function via adjunctive
      cholinergic compounds and antipsychotic crossover approaches are also discussed.

PMID- 16966471
TI  - Prostaglandin E2 receptor EP4 contributes to inflammatory pain hypersensitivity.
AB  - Prostaglandin E(2) (PGE(2)) is both an inflammatory mediator released at the site
      of tissue inflammation and a neuromodulator that alters neuronal excitability and
      synaptic processing. The effects of PGE(2) are mediated by four G-protein-coupled
      EP receptors (EP1-EP4). Here we show that the EP4 receptor subtype is expressed
      by a subset of primary sensory dorsal root ganglion (DRG) neurons, and that its
      levels, but not that of the other EP1-3 subtypes, increase in the DRG after
      complete Freund' adjuvant-induced peripheral inflammation. Administration of both
      an EP4 antagonist [AH23848, (4Z)-7-[(rel-1S,2S,5R)-5-((1,1'-biphenyl-4
      yl)methoxy)-2-(4-morpholinyl)-3-oxocyclopentyl]-4-heptenoic acid] and EP4
      knockdown with intrathecally delivered short hairpin RNA attenuates inflammation
      induced thermal and mechanical behavioral hypersensitivity, without changing
      basal pain sensitivity. AH23848 also reduces the PGE(2)-mediated sensitization of
      capsaicin-evoked currents in DRG neurons in vitro. These data suggest that EP4 is
      a potential target for the pharmacological treatment of inflammatory pain.

PMID- 16966472
TI  - State-dependent block of BK channels by synthesized shaker ball peptides.
AB  - Crystal structures of potassium channels have strongly corroborated an earlier
      hypothetical picture based on functional studies, in which the channel gate was
      located on the cytoplasmic side of the pore. However, accessibility studies on
      several types of ligand-sensitive K(+) channels have suggested that their
      activation gates may be located near or within the selectivity filter instead. It
      remains to be determined to what extent the physical location of the gate is
      conserved across the large K(+) channel family. Direct evidence about the
      location of the gate in large conductance calcium-activated K(+) (BK) channels,
      which are gated by both voltage and ligand (calcium), has been scarce. Our
      earlier kinetic measurements of the block of BK channels by internal quaternary
      ammonium ions have raised the possibility that they may lack a cytoplasmic gate.
      We show in this study that a synthesized Shaker ball peptide (ShBP) homologue
      acts as a state-dependent blocker for BK channels when applied internally,
      suggesting a widening at the intracellular end of the channel pore upon gating.
      This is consistent with a gating-related conformational change at the cytoplasmic
      end of the pore-lining helices, as suggested by previous functional and
      structural studies on other K(+) channels. Furthermore, our results from two BK
      channel mutations demonstrate that similar types of interactions between ball
      peptides and channels are shared by BK and other K(+) channel types.

PMID- 16966473
TI  - Acute oxygen sensing in heme oxygenase-2 null mice.
AB  - Hemeoxygenase-2 (HO-2) is an antioxidant enzyme that can modulate recombinant
      maxi-K(+) channels and has been proposed to be the acute O(2) sensor in the
      carotid body (CB). We have tested the physiological contribution of this enzyme
      to O(2) sensing using HO-2 null mice. HO-2 deficiency leads to a CB phenotype
      characterized by organ growth and alteration in the expression of stress
      dependent genes, including the maxi-K(+) channel alpha-subunit. However,
      sensitivity to hypoxia of CB is remarkably similar in HO-2 null animals and their
      control littermates. Moreover, the response to hypoxia in mouse and rat CB cells
      was maintained after blockade of maxi-K(+) channels with iberiotoxin. Hypoxia
      responsiveness of the adrenal medulla (AM) (another acutely responding O(2)
      sensitive organ) was also unaltered by HO-2 deficiency. Our data suggest that
      redox disregulation resulting from HO-2 deficiency affects maxi-K(+) channel gene
      expression but it does not alter the intrinsic O(2) sensitivity of CB or AM
      cells. Therefore, HO-2 is not a universally used acute O(2) sensor.

PMID- 16966476
TI  - Role of the agonist binding site in up-regulation of neuronal nicotinic
      alpha4beta2 receptors.
AB  - Long-term exposure to nicotinic ligands results in up-regulation of neuronal
      nicotinic alpha4beta2 receptors in the brain and in heterologous expression
      systems. Up-regulation can be produced by a variety of drugs, including nicotinic
      agonists and competitive antagonists, but previous studies have indicated that
      the signal for up-regulation does not reflect a traditional nicotinic
      pharmacology, and the initial steps in signal transduction are not clear. We
      examined the signal for up-regulation and the possible involvement of the
      nicotine binding site in signal reception using mutated subunits transiently
      expressed in human embryonic kidney 293 cells. The data indicate that receptor
      activation and desensitization are not part of the signaling pathway. However,
      mutations to residues in the binding site can affect up-regulation. These results
      provide evidence that the binding site is directly involved in receiving the
      signal for up-regulation.

PMID- 16966475
TI  - The two ATP binding sites of cystic fibrosis transmembrane conductance regulator
      (CFTR) play distinct roles in gating kinetics and energetics.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR), a member of the ABC
      (ATP binding cassette) transporter family, is a chloride channel whose activity
      is controlled by protein kinase-dependent phosphorylation. Opening and closing
      (gating) of the phosphorylated CFTR is coupled to ATP binding and hydrolysis at
      CFTR's two nucleotide binding domains (NBD1 and NBD2). Recent studies present
      evidence that the open channel conformation reflects a head-to-tail dimerization
      of CFTR's two NBDs as seen in the NBDs of other ABC transporters (Vergani et al.,
      2005). Whether these two ATP binding sites play an equivalent role in the
      dynamics of NBD dimerization, and thus in gating CFTR channels, remains
      unsettled. Based on the crystal structures of NBDs, sequence alignment, and
      homology modeling, we have identified two critical aromatic amino acids (W401 in
      NBD1 and Y1219 in NBD2) that coordinate the adenine ring of the bound ATP.
      Conversion of the W401 residue to glycine (W401G) has little effect on the
      sensitivity of the opening rate to [ATP], but the same mutation at the Y1219
      residue dramatically lowers the apparent affinity for ATP by >50-fold, suggesting
      distinct roles of these two ATP binding sites in channel opening. The W401G
      mutation, however, shortens the open time constant. Energetic analysis of our
      data suggests that the free energy of ATP binding at NBD1, but not at NBD2,
      contributes significantly to the energetics of the open state. This kinetic and
      energetic asymmetry of CFTR's two NBDs suggests an asymmetric motion of the NBDs
      during channel gating. Opening of the channel is initiated by ATP binding at the
      NBD2 site, whereas separation of the NBD dimer at the NBD1 site constitutes the
      rate-limiting step in channel closing.

PMID- 16966477
TI  - Point mutations in the transmembrane region of GABAB2 facilitate activation by
      the positive modulator N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6
      diamine (GS39783) in the absence of the GABAB1 subunit.
AB  - GABA(B) receptors are heterodimers of two subunits, GABA(B1) (GB1) and GABA(B2)
      (GB2). Agonists such as GABA and baclofen bind to the GB1 subunit only, whereas
      GB2 is essential for G protein activation. Positive allosteric modulators enhance
      the potency and efficacy of agonists at GABA(B) receptors and are of particular
      interest because they lack the sedative and muscle relaxant properties of
      agonists. In this study, we aimed to characterize the interaction of the positive
      modulator N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine
      (GS39783) with the GABA(B) receptor heterodimer. Using functional guanosine 5'-O
      (3-[(35)S]thio)triphosphate binding assays, we observed positive modulation by
      GS39783 in different vertebrate species but not in Drosophila melanogaster.
      However, coexpression of D. melanogaster GB1 with rat GB2 yielded functional
      receptors positively modulated by GS39783. Together with data from rat/D.
      melanogaster GB2 subunit chimeras, this pointed to a critical role of the GB2
      transmembrane region for positive modulation. We further characterized GS39783
      function using point mutations. GS39783 positively modulated GABA responses but
      also showed considerable agonistic activity at heterodimers containing a mutant
      rat GB2 subunit with three amino acid substitutions in transmembrane domain VI.
      It was surprising that in contrast to wild-type rat GB2, this mutant subunit was
      also activated by GS39783 when expressed without GB1. The mutations of both G706T
      and A708P are necessary and sufficient for activation and identify a key region
      for the effect of GS39783 in the GB2 transmembrane region. Our data show that
      mutations of specific amino acids in GB2 can induce agonism in addition to
      positive modulation and facilitate GB2 activation in the absence of GB1.

PMID- 16966474
TI  - Function of a STIM1 homologue in C. elegans: evidence that store-operated Ca2+
      entry is not essential for oscillatory Ca2+ signaling and ER Ca2+ homeostasis.
AB  - 1,4,5-trisphosphate (IP(3))-dependent Ca(2+) signaling regulates gonad function,
      fertility, and rhythmic posterior body wall muscle contraction (pBoc) required
      for defecation in Caenorhabditis elegans. Store-operated Ca(2+) entry (SOCE) is
      activated during endoplasmic reticulum (ER) Ca(2+) store depletion and is
      believed to be an essential and ubiquitous component of Ca(2+) signaling
      pathways. SOCE is thought to function to refill Ca(2+) stores and modulate Ca(2+)
      signals. Recently, stromal interaction molecule 1 (STIM1) was identified as a
      putative ER Ca(2+) sensor that regulates SOCE. We cloned a full-length C. elegans
      stim-1 cDNA that encodes a 530-amino acid protein with approximately 21% sequence
      identity to human STIM1. Green fluorescent protein (GFP)-tagged STIM-1 is
      expressed in the intestine, gonad sheath cells, and spermatheca. Knockdown of
      stim-1 expression by RNA interference (RNAi) causes sterility due to loss of
      sheath cell and spermatheca contractile activity required for ovulation.
      Transgenic worms expressing a STIM-1 EF-hand mutant that constitutively activates
      SOCE in Drosophila and mammalian cells are sterile and exhibit severe pBoc
      arrhythmia. stim-1 RNAi dramatically reduces STIM-1GFP expression, suppresses the
      EF-hand mutation-induced pBoc arrhythmia, and inhibits intestinal store-operated
      Ca(2+) (SOC) channels. However, stim-1 RNAi surprisingly has no effect on pBoc
      rhythm, which is controlled by intestinal oscillatory Ca(2+) signaling, in wild
      type and IP(3) signaling mutant worms, and has no effect on intestinal Ca(2+)
      oscillations and waves. Depletion of intestinal Ca(2+) stores by RNAi knockdown
      of the ER Ca(2+) pump triggers the ER unfolded protein response (UPR). In
      contrast, stim-1 RNAi fails to induce the UPR. Our studies provide the first
      detailed characterization of STIM-1 function in an intact animal and suggest that
      SOCE is not essential for certain oscillatory Ca(2+) signaling processes and for
      maintenance of store Ca(2+) levels in C. elegans. These findings raise
      interesting and important questions regarding the function of SOCE and SOC
      channels under normal and pathophysiological conditions.

PMID- 16966478
TI  - 2,3-butanedione monoxime affects cystic fibrosis transmembrane conductance
      regulator channel function through phosphorylation-dependent and phosphorylation
      independent mechanisms: the role of bilayer material properties.
AB  - 2,3-Butanedione monoxime (BDM) is widely believed to act as a chemical
      phosphatase. We therefore examined the effects of BDM on the cystic fibrosis
      transmembrane regulator (CFTR) Cl(-) channel, which is regulated by
      phosphorylation in a complex manner. In guinea pig ventricular myocytes,
      forskolin-activated whole-cell CFTR currents responded biphasically to external
      20 mM BDM: a rapid approximately 2-fold current activation was followed by a
      slower (tau approximately 20 s) inhibition (to approximately 20% of control). The
      inhibitory response was abolished by intracellular dialysis with the phosphatase
      inhibitor microcystin, suggesting involvement of endogenous phosphatases. The BDM
      induced activation was studied further in Xenopus laevis oocytes expressing human
      epithelial CFTR. The concentration for half-maximal BDM activation (K(0.5)) was
      state-dependent, approximately 2 mM for highly and approximately 20 mM for
      partially phosphorylated channels, suggesting a modulated receptor mechanism.
      Because BDM modulates many different membrane proteins with similar K(0.5)
      values, we tested whether BDM could alter protein function by altering lipid
      bilayer properties rather than by direct BDM-protein interactions. Using
      gramicidin channels of different lengths (different channel-bilayer hydrophobic
      mismatch) as reporters of bilayer stiffness, we found that BDM increases channel
      appearance rates and lifetimes (reduces bilayer stiffness). At 20 mM BDM, the
      appearance rates increase approximately 4-fold (for the longer, 15
      residues/monomer, channels) to approximately 10-fold (for the shorter, 13
      residues/monomer channels); the lifetimes increase approximately 50%
      independently of channel length. BDM thus reduces the energetic cost of bilayer
      deformation, an effect that may underlie the effects of BDM on CFTR and other
      membrane proteins; the state-dependent changes in K(0.5) are consistent with such
      a bilayer-mediated mechanism.

PMID- 16966479
TI  - Vessel wall calcifications at multi-detector row CT angiography in patients with
      peripheral arterial disease: effect on clinical utility and clinical predictors.
AB  - PURPOSE: To evaluate retrospectively the effect of vessel wall calcifications on
      the clinical utility of multi-detector row computed tomographic (CT) angiography
      performed in patients with peripheral arterial disease and to identify clinical
      predictors for the presence of vessel wall calcifications. MATERIALS AND METHODS:
      The study was approved by the hospital institutional review board, and informed
      consent was obtained from all patients. For this study the authors included
      patients from two randomized controlled trials that measured the costs and
      effects of diagnostic imaging in patients with peripheral arterial disease. All
      patients underwent CT angiography and were followed up for 6 months. Clinical
      utility was measured on the basis of therapeutic confidence (rated on a 10-point
      scale) in the results of initial CT angiography and the need for additional
      vascular imaging. Univariable and multivariable logistic and linear regression
      analysis and the area under the receiver operating characteristic curve were used
      to evaluate the effect of vessel wall calcifications on the clinical utility of
      CT angiography and the use of patient characteristics to predict the number of
      calcified segments at CT angiography. RESULTS: A total of 145 patients were
      included (mean age, 64 years; 70% men). The authors found that the number of
      calcified segments was a significant predictor of the need for additional imaging
      (P = .001) and of the confidence scores (P < .001). The number of calcified
      segments discriminated between patients who required additional imaging after CT
      angiography and those who did not (area under the receiver operating
      characteristic curve, 0.66; 95% confidence interval: 0.54, 0.77). Age, diabetes
      mellitus, and cardiac disease were significant predictors of the number of
      calcified segments in both the univariable and multivariable analyses (P < .05).
      CONCLUSION: Vessel wall calcifications decrease the clinical utility of CT
      angiography in patients with peripheral arterial disease. Diabetes mellitus,
      cardiac disease, and elderly age (older than 84 years) are independently
      predictive for the presence of vessel wall calcifications.

PMID- 16966480
TI  - Stage T1 non-small cell lung cancer: preoperative mediastinal nodal staging with
      integrated FDG PET/CT--a prospective study.
AB  - PURPOSE: To prospectively evaluate the sensitivity and specificity of integrated
      fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and
      computed tomography (CT) (PET/CT) for the preoperative diagnosis of mediastinal
      nodal metastasis in stage T1 non-small cell lung cancer (NSCLC), with surgical
      and histologic results as reference standards. MATERIALS AND METHODS:
      Institutional review board approval and informed consent were obtained. From June
      2003 to February 2005, 150 patients (89 men and 61 women; mean age, 59 years)
      with stage T1 NSCLC at stand-alone CT underwent integrated PET/CT and surgical
      staging. Two observers (one radiologist and one nuclear medicine physician)
      evaluated prospectively and in consensus the mediastinal nodes by analyzing both
      PET (functional) and CT (anatomic) images. Nodal stages were determined by using
      the American Joint Committee on Cancer staging system and surgical and histologic
      findings as the reference standard. Statistical evaluation of malignant lymph
      nodes was performed on per-nodal-station and per-person bases. RESULTS: A total
      of 568 mediastinal nodal stations were evaluated. Nodes were positive for
      malignancy in 34 (23%) of 150 patients and 55 (10%) of 568 nodal stations. For
      depiction of malignant nodes, the respective sensitivity, specificity, positive
      predictive value, negative predictive value, and accuracy of integrated PET/CT
      were 42% (23 of 55), 100% (513 of 513), 100% (23 of 23), 94% (513 of 545), and
      94% (536 of 568) on per-nodal-station basis and 47% (16 of 34), 100% (116 of
      116), 100% (16 of 16), 87% (116 of 134), and 88% (132 of 150) on a per-patient
      basis. CONCLUSION: Integrated FDG PET/CT provides high specificity and positive
      predictive value of mediastinal nodal staging in stage T1 NSCLC, although the
      sensitivity is low.

PMID- 16966481
TI  - Liver adenomatosis: classification of MR imaging features and comparison with
      pathologic findings.
AB  - PURPOSE: To retrospectively compare the clinical manifestation and magnetic
      resonance (MR) imaging features of liver adenomatosis with pathologic findings.
      MATERIALS AND METHODS: This study had institutional review board approval, and
      informed consent was waived. Twenty patients were classified on the basis of
      pathologic findings into three groups: those with a steatotic, those with a
      peliotic, and those with a mixed (steatotic and peliotic) form of liver
      adenomatosis. MR images were reviewed in consensus by two abdominal radiologists,
      and findings were compared with the pathologic classification. Statistical
      evaluation was performed with the Student t test. RESULTS: All patients were
      women (mean age, 39 years +/- 10 [standard deviation]). Lesions of the steatotic
      form (n = 7) showed (a) a mean diameter of 6.3 cm +/- 1.7, (b) slightly
      hyperintense signal on T2-weighted images, (c) hyper- or isointense signal on T1
      weighted images with a signal dropout with fat suppression sequences, and (d)
      moderate enhancement at the arterial phase with no delayed enhancement. Lesions
      of the peliotic form (n = 7) showed (a) a somewhat larger size (8.3 cm +/- 3.6),
      (b) markedly hyperintense signal on T2-weighted images, (c) iso- or
      hyperintensity on T1-weighted images with no signal dropout with fat suppression
      sequences, and (d) strong arterial enhancement and persistent enhancement at the
      portal and delayed phase. Lesions of the mixed form (n = 6) included a
      combination of imaging features of the steatotic and peliotic forms. Lesions,
      however, were significantly larger in the mixed form than in the steatotic form
      (10.3 cm +/- 4, P < .05). CONCLUSION: There are three patterns of MR imaging
      features of liver adenomatosis that are associated with three pathologic forms
      (steatotic, peliotic, and mixed).

PMID- 16966482
TI  - Inflammation in carotid atherosclerotic plaque: a dynamic contrast-enhanced MR
      imaging study.
AB  - PURPOSE: To prospectively evaluate if there is an association between plaque
      enhancement at magnetic resonance (MR) imaging and proinflammatory cardiovascular
      risk factors and plaque content. MATERIALS AND METHODS: This study was performed
      with informed consent, HIPAA compliance, and institutional review board approval.
      Contrast agent dynamics within carotid plaques were measured in 30 patients (29
      men, one woman; mean age, 67.7 years +/- 10.7 [standard deviation]) who were
      scheduled to undergo carotid endarterectomy. Measurements were based on kinetic
      modeling of images obtained at 15-second intervals during which a gadolinium
      based contrast agent was injected. The time-varying signal intensities within the
      plaques were used to estimate the fractional plasma volume (vp) and transfer
      constant (Ktrans) of contrast material into the extracellular space. Pearson
      correlation coefficients were computed between blinded MR measurements and
      histologic measurements of plaque composition, including macrophages,
      neovasculature, necrotic core, calcification, loose matrix, and dense fibrous
      tissue. Correlation coefficients or mean differences were computed regarding
      clinical markers of cardiovascular risk. RESULTS: Analyzable MR images and
      histologic results were obtained in 27 patients. Measurements of Ktrans
      correlated with macrophage (r = 0.75, P < .001), neovasculature (r = 0.71, P <
      .001), and loose matrix (r = 0.50, P = .01) content. Measurements of v(p)
      correlated with macrophage (r = 0.54, P = .004), neovasculature (r = 0.68, P <
      .001), and loose matrix (r = 0.42, P = .03) content. For clinical parameters,
      significant associations were correlated with Ktrans only, with decreased high
      density lipoprotein levels (r = -0.66, P < .001) and elevated Ktrans measurements
      in smokers compared with nonsmokers (mean, 0.134 min(-1) vs 0.074 min(-1),
      respectively; P = .01). CONCLUSION: The correlations between Ktrans and
      histologic markers of inflammation suggest that Ktrans is a quantitative and
      noninvasive marker of plaque inflammation, which is further supported by the
      correlation of Ktrans with proinflammatory cardiovascular risk factors, decreased
      high-density lipoprotein levels, and smoking.

PMID- 16966483
TI  - Noninvasive coronary angiography with 64-section CT: effect of average heart rate
      and heart rate variability on image quality.
AB  - PURPOSE: To evaluate prospectively the effect of average heart rate and heart
      rate variability on image quality at 64-section computed tomographic (CT)
      coronary angiography. MATERIALS AND METHODS: The study protocol had local ethics
      committee approval; written informed consent was obtained. There were 125
      patients (45 women, 80 men; mean age, 59.9 years +/- 12.9 [standard deviation];
      79 receiving beta-blockers) who underwent 64-section CT coronary angiography with
      retrospective electrocardiographic gating. Data sets were reconstructed in 5%
      steps from 20% to 80% of R-R interval. Heart rate variability was calculated as 1
      standard deviation from mean rate during scanning. Two observers rated image
      quality of each coronary segment at least 1.5-mm diameter (1 = no motion
      artifacts, 5 = not evaluative). Repeated analysis of variance measurements were
      performed to evaluate quantitative parameters. Pearson correlation analysis was
      performed to compare image quality in each patient with average heart rate and
      heart rate variability. RESULTS: Average heart rate was 63.3 beats per minute +/-
      13.1, with variability of 3.2 beats per minute +/- 2.1. Diagnostic image quality
      (score < or = 3) was attained in 1821 of 1836 segments at the best reconstruction
      interval. There was no correlation between mean heart rate and image quality for
      all segments of the right coronary and left anterior descending arteries, but
      there was a significant correlation for left circumflex artery (r = 0.33, P <
      .05). Heart rate variability was correlated with image quality overall (r = 0.75,
      P < .001) and for each coronary artery. Heart rate was less variable and image
      quality was better (P < .05) in patients receiving beta-blockers. Best image
      quality was obtained in diastole with heart rate less than 80 beats per minute
      and in systole with faster heart rate. CONCLUSION: Coronary angiography with 64
      section CT provides diagnostic image quality within a wide range of heart rates.
      Reducing average heart rate and heart rate variability is beneficial for reducing
      artifacts.

PMID- 16966484
TI  - Prostate cancer localization with dynamic contrast-enhanced MR imaging and proton
      MR spectroscopic imaging.
AB  - PURPOSE: To prospectively determine the accuracies of T2-weighted magnetic
      resonance (MR) imaging, dynamic contrast material-enhanced MR imaging, and
      quantitative three-dimensional (3D) proton MR spectroscopic imaging of the entire
      prostate for prostate cancer localization, with whole-mount histopathologic
      section findings as the reference standard. MATERIALS AND METHODS: This study was
      approved by the institutional review board, and informed consent was obtained
      from all patients. Thirty-four consecutive men with a mean age of 60 years and a
      mean prostate-specific antigen level of 8 ng/mL were examined. The median biopsy
      Gleason score was 6. T2-weighted MR imaging, dynamic contrast-enhanced MR
      imaging, and 3D MR spectroscopic imaging were performed, and on the basis of the
      image data, two readers with different levels of experience recorded the location
      of the suspicious peripheral zone and central gland tumor nodules on each of 14
      standardized regions of interest (ROIs) in the prostate. The degree of diagnostic
      confidence for each ROI was recorded on a five-point scale. Localization accuracy
      and ROI-based receiver operating characteristic (ROC) curves were calculated.
      RESULTS: For both readers, areas under the ROC curve for T2-weighted MR, dynamic
      contrast-enhanced MR, and 3D MR spectroscopic imaging were 0.68, 0.91, and 0.80,
      respectively. Reader accuracy in tumor localization with dynamic contrast
      enhanced imaging was significantly better than that with quantitative
      spectroscopic imaging (P < .01). Reader accuracy in tumor localization with both
      dynamic contrast-enhanced imaging and spectroscopic imaging was significantly
      better than that with T2-weighted imaging (P < .01). CONCLUSION: Compared with
      use of T2-weighted MR imaging, use of dynamic contrast-enhanced MR imaging and 3D
      MR spectroscopic imaging facilitated significantly improved accuracy in prostate
      cancer localization.

PMID- 16966486
TI  - Differential role of Jak-STAT signaling in retinal degenerations.
AB  - Retinal degeneration is a major cause of severe visual impairment or blindness.
      Understanding the underlying molecular mechanisms is a prerequisite to develop
      therapeutic approaches for human patients. We show in three mouse models that
      induced and inherited retinal degeneration induces LIF and CLC as members of the
      interleukin (IL)-6 family of proteins, activates proteins of the Jak-STAT
      signaling pathway, and up-regulates suppressors of cytokine signaling as a
      negative feedback loop. Inhibition of Jak2 leads to protection of photoreceptors
      in a model of induced but not in a model of inherited retinal degeneration.
      Differential activation of Akt suggests alternative pathways for cell death
      and/or survival in different models. Proteins induced during photoreceptor
      degeneration are not mainly expressed in photoreceptors but in cells of other
      retinal layers. This suggests a model in which photoreceptor injury is signaled
      to cells of the inner retina, which in turn initiate a response either to support
      viability or accelerate death of injured cells.

PMID- 16966485
TI  - Prodynorphin storage and processing in axon terminals and dendrites.
AB  - The classical view postulates that neuropeptide precursors in neurons are
      processed into mature neuropeptides in the somatic trans-Golgi network (TGN) and
      in secretory vesicles during axonal transport. Here we show that prodynorphin
      (PDYN), precursor to dynorphin opioid peptides, is predominantly located in axon
      terminals and dendrites in hippocampal and striatal neurons. The molar content of
      unprocessed PDYN was much greater than that of dynorphin peptides in axon
      terminals of PDYN-containing neurons projecting to the CA3 region of the
      hippocampus and in the striatal projections to the ventral tegmental area.
      Electron microscopy showed coexistence of PDYN and dynorphins in the same axon
      terminals with occasional codistribution in individual dense core vesicles. Thus,
      the precursor protein is apparently stored at presynaptic sites. In comparison
      with the hippocampus and striatum, PDYN and dynorphins were more equally
      distributed between neuronal somata and processes in the amygdala and cerebral
      cortex, suggesting regional differences in the regulation of trafficking and
      processing of the precursor protein. Potassium-induced depolarization activated
      PDYN processing and secretion of opioid peptides in neuronal cultures and in a
      model cell line. Regulation of PDYN storage and processing at synapses by
      neuronal activity or extracellular stimuli may provide a local mechanism for
      regulation of synaptic transmission.

PMID- 16966487
TI  - Mast cells are required for normal healing of skin wounds in mice.
AB  - Mast cells (MCs) have recently been reported to play a pivotal role in the
      elicitation of inflammatory reactions that are beneficial to the host, e.g.,
      during innate immune responses to bacteria. To explore whether MCs also
      contribute to wound repair, we studied experimentally induced skin wounds in MC
      deficient Kit(W)/Kit(W-v) mice, normal Kit+/+ mice, and MC-reconstituted
      Kit(W)/Kit(W-v) mice. Wound closure was significantly impaired in the absence of
      MCs during the first 6 days of wound healing and histomorphometric analyses of MC
      degranulation at the wound edges revealed distance-dependent MC activation, i.e.,
      MC degranulation was most prominent directly adjacent to the wound. In addition,
      Kit(W)/Kit(W-v) mice showed impaired extravasation and recruitment of neutrophils
      to the wounded areas. Notably, wound closure, extravasation, and neutrophil
      recruitment were found to be normal in MC-reconstituted Kit(W)/Kit(W-v) mice.
      Therefore, we examined whether MCs promote wound healing by releasing histamine
      or TNF-alpha. Interestingly, wound closure was reduced in mice treated with an H1
      receptor antagonist but not after treatment with an H2-receptor antagonist or in
      the absence of TNF-alpha. Taken together, our findings indicate that MC
      activation and histamine release are required for normal cutaneous wound healing.

PMID- 16966488
TI  - Genistein, a soy isoflavone, up-regulates expression of antioxidant genes:
      involvement of estrogen receptors, ERK1/2, and NFkappaB.
AB  - We have previously reported that estrogens up-regulate longevity-associated
      genes. As recent evidence has shown that estrogen replacement therapy is
      associated with an increased risk of cardiovascular disease, we have studied the
      effects of genistein, a soy isoflavone with a similar structure to estradiol, on
      the expression of antioxidant, longevity-related genes. MCF-7 cells (human
      mammary gland tumor cell line) were incubated for 48 h with 0.5 microM genistein,
      a concentration found in the plasma of populations consuming diets rich in soy
      protein. Peroxide levels were determined by fluorimetry, activation of
      extracellular-signal regulated kinase (ERK1/2), and nuclear factor kappaB
      (NFkappaB)-signaling pathways by Western blot analysis and ELISA, respectively,
      and mRNA expression of antioxidant genes by real-time reverse transcriptase
      polymerase chain reaction (RT-PCR). Inhibition of basal peroxide levels in MCF-7
      cells by genistein was prevented by pretreatment of cells with the estrogen
      receptor antagonist tamoxifen. Phosphorylation of extracellular regulated kinase
      (ERK)1/2 led to an activation of NFkappaB, as indicated by increased p50 subunit
      expression in nuclear extracts, and increased mRNA levels of the antioxidant
      enzyme manganese-superoxide dismutase (MnSOD). Inhibition of ERK1/2 abrogated
      genistein-mediated NFkappaB activation and elevated expression of MnSOD. Our
      molecular studies may provide a basis to determine the effects of genistein and
      other soy protein-derived products on longevity in both animals and the human
      population.

PMID- 16966489
TI  - Capturing complexity: integrating health and education research to inform health
      promoting schools policy and practice.
AB  - Despite the intersectoral nature of health promotion practice many programs limit
      their evidence base to health sector research and do not draw on evidence from
      other sectors' research in program design. To help ensure programs are relevant
      and acceptable to intersectoral partners and intended outcomes are of value to
      all sectors involved, utilising evidence from more than one discipline is
      essential. This article identifies the narrow interpretation of existing evidence
      for health promoting schools and discusses the challenges faced by practitioners
      and policy makers when reviewing evidence. These issues include the various
      perspectives on what is 'quality' evidence and how to ensure multidisciplinary
      evidence is used to inform practice, particularly with the education sector that
      has a strong research base of its own. A data extraction tool was developed to
      help address these issues and assist the design of a health promoting schools
      program. A description of the tool's elements and two case studies provide
      examples of how research from two different disciplines can be integrated to
      inform planning and strengthen partnerships. The tool expands the evidence base
      for policy and practice decision-making for health promoting schools,
      acknowledging the practical realities of both sectors.

PMID- 16966490
TI  - The neural correlates of human working memory for haptically explored object
      orientations.
AB  - Skillful object manipulation requires that haptically explored spatial object
      characteristics like orientation be adequately represented in working memory. In
      the current functional magnetic resonance imaging study, healthy right-handed
      participants explored a bar-shaped reference object with the left hand,
      memorizing its orientation. After a variable delay (0.5, 5, or 10 s),
      participants used their right hand to match the orientation by rotating a second,
      identical object. In the first seconds of the delay, right sensorimotor cortex
      was active, whereas clusters in left anterior prefrontal cortex (aPFC) (Brodmann
      area 10) became dominant 2 s after the end of exploration, showing sustained
      activity for several seconds. In contrast, left parieto-occipital cortex was
      involved toward the end of the delay interval. Our results indicate that a
      dynamic network of brain areas subserves hapticospatial information processing in
      the delay between haptic stimulus exploration and orientation matching. We
      propose that haptic sensory traces, maintained in contralateral sensorimotor
      cortex, are transformed into more abstract hapticospatial representations in the
      early delay stages. Maintenance of these representations engages aPFC and parieto
      occipital cortex. Whereas aPFC possibly integrates spatial and motor components
      of hapticospatial working memory, parieto-occipital cortex might be involved in
      orientation imagery, supporting working memory, and the preparation of haptic
      matching.

PMID- 16966491
TI  - The lipid-lowering effect of ezetimibe in pure vegetarians.
AB  - Results of previous studies have shown that ezetimibe (10 mg/day) reduces LDL
      cholesterol in patients with mild hypercholesterolemia on a normal-cholesterol
      diet (dietary intake of 200-500 mg/day) by 16-22%. However, the LDL cholesterol
      lowering effect of ezetimibe in subjects with an extremely low dietary
      cholesterol intake (vegetarians) has not been studied. We conducted a randomized,
      double-blind, placebo-controlled, two-phase crossover study in 18 healthy pure
      vegetarians to assess the effect of ezetimibe (10 mg/day) on plasma lipids,
      cholesterol absorption, and its synthesis. Treatment periods lasted 2 weeks each,
      with an intervening 2 week washout period. Fractional cholesterol absorption was
      determined using the continuous dual stable isotope feeding method. Mean dietary
      cholesterol intake in the pure vegetarians was extremely low and averaged 29.4 +/
      16.8 and 31.4 +/- 14.4 mg/day during the placebo and ezetimibe administration
      phases, respectively. Fractional cholesterol absorption during the placebo phase
      was 48.2 +/- 8.2% and was decreased by 58% during ezetimibe treatment to 20.2 +/-
      6.2% (P < 0.001). This change in intestinal cholesterol absorption was followed
      by a significant reduction in LDL cholesterol of 17.3%. In individuals with
      extremely low dietary cholesterol intake, treatment with ezetimibe (10 mg/day)
      leads to a significant reduction of cholesterol absorption and a clinically
      relevant decrease of plasma LDL cholesterol, comparable to that of subjects with
      a normal dietary cholesterol intake. Thus, the lipid-lowering effect of ezetimibe
      is mediated mainly through a reduction of the absorption of endogenous (biliary)
      cholesterol.

PMID- 16966492
TI  - Acute hyperinsulinemia inhibits intramyocellular triglyceride synthesis in high
      fat-fed obese rats.
AB  - Hyperinsulinemia is common in obesity, but whether it plays a role in
      intramyocellular triglyceride (imcTG) buildup is unknown. In this study,
      hyperinsulinemic-euglycemic clamp experiments were performed in overnight-fasted
      lean and high-fat-fed obese rats, awake, to determine the effect of insulin on
      imcTG synthesis (incorporation of [(14)C]glycerol, [(14)C]glucose, and
      [(3)H]oleate). Insulin infusion at 25 (low insulin) and 100 (high insulin)
      pmol/kg/min increased plasma insulin by 5- and 16-fold, respectively, whereas
      plasma and intramyocellular glycerol, FFAs, triglycerides, and glucose levels
      were maintained at their basal levels by co-infusion of exogenous glycerol, FFAs,
      and triglycerides at fixed rates and glucose at varying rates. In obese rats,
      insulin suppressed incorporation of glycerol into the imcTG-glycerol moiety dose
      dependently (P < 0.01-P < 0.001) in gastrocnemius and tibialis anterior, but only
      the high insulin suppressed it in soleus (P < 0.05). The low insulin suppressed
      glucose incorporation into imcTG-glycerol in all three muscles (P = 0.01-P <
      0.01). However, the low insulin did not affect (P > 0.05) and the high insulin
      suppressed (P < 0.05-P < 0.01) fatty acid incorporation into imcTG in all three
      muscles. Insulin also suppressed glycerol incorporation in lean rats (P < 0.01-P
      < 0.04). On the other hand, imcTG pool size was not affected by insulin (P >
      0.05). These observations suggest that acute hyperinsulinemia inhibits imcTG
      synthesis and thus does not appear to promote imcTG accumulation via the
      synthetic pathway, at least in the short term.

PMID- 16966493
TI  - Constant rate of steady-state self-antigen trafficking from skin to regional
      lymph nodes.
AB  - It is suggested that dendritic cells (DCs) capture and present both foreign
      antigens such as components of pathogens as well as endogenous self-antigens.
      However, the magnitude of self-antigen trafficking to secondary lymphoid organs
      is still unclear. Here we show constitutive trafficking of self-antigens from
      skin to regional lymph nodes (LNs) quantitatively using a KRT14-Kitl transgenic
      mouse. This mouse model expresses the Kit ligand in keratinocytes, shows
      hyperpigmentation of the epidermis and exhibits constitutive accumulation of
      melanin granules (MGs) in skin regional LNs transported by Langerhans cells.
      Using an MG-solubilization technique, we revealed that 128 microg per week of
      MGs, a marker of self-antigens, accumulated in skin regional LNs and that the
      rate of accumulation was constant from 3 to 50 weeks. Activation markers such as
      CD40, CD54 and CD86 did not increase in the LNs, and abrogation of CD40 signaling
      did not affect the accumulation. Additionally, the total amount of MGs did not
      increase significantly following stimulation with intravenous LPS injections.
      These results suggest that the accumulation is not caused by inflammatory
      stimuli, and the steady-state trafficking of self-antigens is intrinsically
      maintained at a constant rate. Because the levels of self-antigens as well as the
      phenotype of these DCs are thought to be important in the strength of immune
      responses, the results may imply that the constant rate of trafficking of self
      antigens is required for maintaining homeostatic conditions, such as self
      tolerance.

PMID- 16966494
TI  - Dendritic cell activating peptides induce distinct cytokine profiles.
AB  - High-mobility group box 1 protein (HMGB1), a DNA-binding nuclear and cytosolic
      protein, is a pro-inflammatory cytokine released by monocytes and macrophages.
      HMGB1 as well as its B box domain induce maturation of human dendritic cells
      (DCs). This report demonstrates that the B box domain induces phenotypic
      maturation of murine bone marrow-derived dendritic cells (BM-DCs) as evidenced by
      increased CD86, CD40 and MHC-II expression. The B box domain enhanced secretion
      of pro-inflammatory cytokines and chemokines: IL-1beta, IL-2, IL-5, IL-8, IL-12
      and tumor necrosis factor (TNF)-alpha, but not IL-6 and IL-10. Furthermore, four
      peptides whose sequences correspond to different regions of HMGB1 induced
      production of IL-1beta, IL-2 and IL-12 (p70), but not IL-10 and IL-6 in mouse BM
      DCs. Interestingly, these peptides differed in their capacity to induce TNF
      alpha, IL-5, IL-18 and IL-8. B box domain as well as peptide-activated DCs acted
      as potent stimulators of allogeneic T cells in a mixed leukocyte reaction. DCs
      exposed to HMGB1 peptides induced proliferation of ovalbumin-specific syngeneic T
      cells. These DC-activating peptides could serve as an adjuvant in
      immunotherapeutic or vaccine context and the selective activity of these
      different peptides suggests a means to customize the functional properties of
      DCs.

PMID- 16966495
TI  - TCR transgenic CD8+ T cells activated in the presence of TGFbeta express FoxP3
      and mediate linked suppression of primary immune responses and cardiac allograft
      rejection.
AB  - Although CD4+CD25+FoxP3+ regulatory T cells play a role in allograft tolerance,
      the role of CD8+ cells with immunosuppressive function is less clear. To address
      this issue, spleen cells from Rag-1-deficient TCR transgenic (Tg) mice expressing
      a receptor for ovalbumin (OVA) in the context of MHC class I (OT1) were activated
      with OVA expressing antigen-presenting cell (APC) in the presence or absence of
      exogenous transforming growth factor beta (TGFbeta). TGFbeta inhibited the
      expression of IFN-gamma, granzyme B and the lytic activity of the OT1 T cells
      while inducing FoxP3 expression in 5-15% of the cells. By contrast, FoxP3
      expression was not detected in naive OT-1 T cells or OT-1 T cells activated
      without exogenous TGFbeta. TGFbeta-activated OT1 cells inhibited the activation
      of Kd-specific CD8+ CTL responses by normal B6 T cells and the proliferation by
      Kd-specific CD4+ TCR Tg T cells, but only if the OVA epitope was co-expressed by
      Kd+ APC. This antigen-specific inhibitory activity, referred to as linked
      suppression, was neither mediated by residual lytic activity within the activated
      OT1 T cells nor did it depend upon IL-10 or TGFbeta. Suppression correlated with
      inhibition of CD86 expression on CD11c+ APC. TGFbeta-activated OT1 T cells also
      delayed the rejection of heterotopic, vascularized cardiac allografts mediated by
      anti-Kd-specific CD4+ TCR Tg T cells, but only if the cardiac allograft expressed
      both OVA and Kd as transgenes. Prolonged survival of allografts was associated
      with rapid migration of the FoxP3+ OT1 T cells into the donor heart raising the
      possibility that suppression may be mediated within the allograft. These data
      show that TGFbeta-activated CD8+ T cells mediate antigen-specific, APC-focused
      patterns of suppression in vitro and in vivo.

PMID- 16966496
TI  - CD27 contributes to the early systemic immune response to Mycobacterium
      tuberculosis infection but does not affect outcome.
AB  - The development of a strong Th1-mediated adaptive immune response is considered
      of main importance for host defense against the intracellular pathogen
      Mycobacterium tuberculosis. The induction of a cellular immune response is not
      only dependent on the engagement of the TCR but also requires co-stimulation. In
      order to study the role of the co-stimulatory molecule of the tumor necrosis
      factor receptor family member CD27 during murine M. tuberculosis infection, we
      intranasally infected wild-type (WT) and CD27 knockout (KO) mice with 10(5)
      colony-forming units M. tuberculosis. Whereas there were no differences in
      bacterial growth, inflammation and IFNgamma production by CD4+ and CD8+
      lymphocytes in the lungs early after infection, the number of splenic CD8+ T
      cells producing the key Th1 cytokine IFNgamma was lower in CD27 KO mice than in
      WT mice. After 6 weeks, CD27 KO mice had 3.6-fold higher mycobacterial counts in
      their lungs and displayed more pulmonary inflammation and increased numbers of
      infiltrated leukocytes. Despite these differences early in infection, an equal
      number of WT and CD27 KO mice died during a 43-week observation period and lung
      bacterial loads and inflammation were comparable in the surviving animals. Our
      data suggest that CD27 does not contribute to the local IFNgamma-mediated
      response and long-term protection against M. tuberculosis.

PMID- 16966497
TI  - Effectiveness of intranasal zolmitriptan in acute cluster headache: a randomized,
      placebo-controlled, double-blind crossover study.
AB  - BACKGROUND: Cluster headache is a form of primary headache in which attacks are
      rapid in onset with very severe pain. The mainstays of acute therapy are inhaled
      oxygen and sumatriptan succinate injection. OBJECTIVE: To evaluate zolmitriptan
      nasal spray in the acute treatment of cluster headache. METHODS: Ninety-two
      patients, aged 40 +/- 10 years (mean +/- SD) (80 men and 12 women), with
      International Headache Society-defined cluster headache were randomized into a
      placebo-controlled, double-blind crossover study. Patients treated 3 headache
      attacks using placebo for 1 attack, 5 mg of zolmitriptan nasal spray (ZNS5) for 1
      attack, and 10 mg of zolmitriptan nasal spray for 1 attack. The primary end point
      was headache relief at 30 minutes, defined as reduction from moderate, severe, or
      very severe pain to no or mild pain. The study was approved by the appropriate
      ethics committees. RESULTS: Sixty-nine patients were available for an intention
      to-treat analysis. The 30-minute headache relief rates were placebo, 21%; ZNS5,
      40%; and ZNS10, 62%. Modeling the response as a binary outcome, the Wald test was
      significant for the overall regression (chi(2)(1) = 29.4; P<.001), with both ZNS5
      and ZNS10 giving significant effects against placebo. Headache relief rates for
      patients with episodic cluster headache were 30% for placebo, 47% for ZNS5, and
      80% for ZNS10, while corresponding rates for patients with chronic cluster
      headache were 14%, 28%, and 36%, respectively. Zolmitriptan was also well
      tolerated. CONCLUSION: Five-milligram and 10-mg doses of zolmitriptan intranasal
      spray are effective within 30 minutes and well tolerated in the treatment of
      acute cluster headache. Trial Registration controlled-trials.com Identifier
      ISCRTN27362692.

PMID- 16966498
TI  - The importance of LRRK2 mutations in Parkinson disease.

PMID- 16966499
TI  - Genetic testing in Parkinson disease: promises and pitfalls.

PMID- 16966500
TI  - A parietofrontal network for spatial awareness in the right hemisphere of the
      human brain.

PMID- 16966501
TI  - Clinical heterogeneity of the LRRK2 G2019S mutation.
AB  - BACKGROUND: Several pathogenic mutations have been reported in the leucine-rich
      repeat kinase 2 gene (LRRK2) that cause parkinsonism. The "common" LRRK2 G2019S
      kinase domain substitution has been reported to account for approximately 5% of
      familial and 1% of sporadic Parkinson disease. OBJECTIVE: To observe the clinical
      heterogeneity presented by LRRK2 kinase mutation carriers. DESIGN, SETTING, AND
      PARTICIPANTS: We screened 130 patients with pathologically confirmed Parkinson
      disease and 85 controls for 3 LRRK2 kinase domain pathogenic substitutions:
      I2012T, G2019S, and I2020T. MAIN OUTCOME MEASURES: Detailed clinical phenotypes
      for individuals who screened positive for LRRK2 mutations. RESULTS: Five LRRK2
      G2019S carriers were identified, of whom 4 had Parkinson disease (clinically and
      pathologically confirmed), and the fifth was a control subject who died at age 68
      years after an acute myocardial infarction with no evidence of neurodegenerative
      abnormalities. There was no evidence of the I2012T or I2020T mutation in these
      participants. CONCLUSIONS: The underlying disease mechanisms of LRRK2 G2019S
      associated parkinsonism are similar to those of typical Parkinson disease. The
      identification of a control subject raises important questions concerning genetic
      diagnosis and counseling.

PMID- 16966502
TI  - Clinical features of Parkinson disease patients with homozygous leucine-rich
      repeat kinase 2 G2019S mutations.
AB  - BACKGROUND: The G2019S mutation is the most common pathogenic substitution in the
      leucine-rich repeat kinase 2 (LRRK2) gene, which has recently been identified in
      familial and sporadic Parkinson disease (PD). OBJECTIVES: To report the clinical
      characteristics of PD patients with homozygous LRRK2 6055G>A (G2019S) mutations
      and to compare them with previously published descriptions of heterozygous
      patients. DESIGN: Descriptive clinical report from an international consortium of
      studies. Subjects Patients with familial PD and homozygous LRRK2 mutations
      included 23 Tunisians, 2 Algerians, 2 US patients, 1 Canadian, and 1 Moroccan.
      RESULTS: There were no observable differences between the homozygote and
      heterozygote phenotypes. CONCLUSIONS: Parkinson disease related to LRRK2 is
      characterized by typical clinical features, and the similarities between patients
      with homozygous and heterozygous mutations do not support a gene dosage effect.

PMID- 16966503
TI  - Juvenile-onset Parkinsonism as a result of the first mutation in the adenosine
      triphosphate orientation domain of PINK1.
AB  - BACKGROUND: Mutations in the PTEN-induced putative kinase 1 (PINK1) gene at 1p36
      have been involved in autosomal recessive early-onset parkinsonism. OBJECTIVE: To
      describe the clinical and genetic features of the largest kindred reported to
      date with early-onset parkinsonism associated with the PINK1 gene. DESIGN:
      Clinical and genetic study. SETTING: Collaborative study. Patients Eight patients
      from Sudan with particularly early onset (ages 9-17 years) and phenotypes varying
      from dopa-responsive dystonia-like to typical early-onset parkinsonism. MAIN
      OUTCOME MEASURES: The PINK1 genotype and Parkinson disease status of all
      available family members. RESULTS: The disease was caused by a novel mutation,
      p.A217D, located in the highly conserved adenosine triphosphate orientation site
      of the PINK1 kinase domain. CONCLUSION: This study extends the phenotypic and
      molecular spectrum of the PINK1 gene and the geographic origin of patients with
      PINK1 gene mutations.

PMID- 16966504
TI  - Frequency-dependent reciprocal modulation of verbal fluency and motor functions
      in subthalamic deep brain stimulation.
AB  - BACKGROUND: High-frequency deep brain stimulation (DBS) of the subthalamic
      nucleus (STN) improves motor functions in those with Parkinson disease but may
      worsen frontal functions such as verbal fluency (VF). In contrast, low-frequency
      DBS leads to deterioration of motor functions. It is not known whether low
      frequency STN DBS also has an effect on frontal functions. OBJECTIVE: To examine
      whether low-frequency STN DBS in contrast to high-frequency STN DBS has a
      positive effect on frontal functions on the basis of VF test results. DESIGN: A
      double-blind randomized crossover experiment to compare performance in 4 VF
      subtests and motor performance at 10 Hz, 130 Hz, and no stimulation. SETTING:
      University hospitals in Dusseldorf and Cologne, Germany. PATIENTS: Twelve
      patients with Parkinson disease 3 months or more after bilateral electrode
      implantation into the STN. MAIN OUTCOME MEASURE: Mean number of words in VF at
      different stimulation frequencies. RESULTS: The VF was significantly better at 10
      Hz (48.3 words) compared with 130 Hz and showed a nonsignificant trend toward
      worsening at 130 Hz (42.3 words) compared with no stimulation (43.8 words). These
      results were consistent across all subtests. CONCLUSIONS: The study provides
      evidence of a beneficial effect of low-frequency (10 Hz) STN DBS on VF, which may
      be caused by activating neural pathways projecting to the frontal cortex. In
      addition, the study reproduces the negative effect of therapeutic high-frequency
      STN DBS on VF. The study results provide evidence for a frequency-dependent
      modulation of cognitive circuits involving the STN.

PMID- 16966505
TI  - Neurochemical aftermath of amateur boxing.
AB  - BACKGROUND: Little solid information is available on the possible risks for
      neuronal injury in amateur boxing. OBJECTIVE: To determine whether amateur boxing
      and severity of hits are associated with elevated levels of biochemical markers
      for neuronal injury in cerebrospinal fluid. DESIGN: Longitudinal study. SETTING:
      Referral center specializing in evaluation of neurodegenerative disorders.
      PARTICIPANTS: Fourteen amateur boxers (11 men and 3 women) and 10 healthy male
      nonathletic control subjects. INTERVENTIONS: The boxers underwent lumbar puncture
      7 to 10 days and 3 months after a bout. The control subjects underwent LP once.
      MAIN OUTCOME MEASURES: Neurofilament light protein, total tau, glial fibrillary
      acidic protein, phosphorylated tau, and beta-amyloid protein 1-40 (Abeta([1-40]))
      and 1-42 (Abeta([1-42])) concentrations in cerebrospinal fluid were measured.
      RESULTS: Increased levels after a bout compared with after 3 months of rest from
      boxing were found for 2 markers for neuronal and axonal injury, neurofilament
      light protein (mean +/- SD, 845 +/- 1140 ng/L vs 208 +/- 108 ng/L; P = .008) and
      total tau (mean +/- SD, 449 +/- 176 ng/L vs 306 +/- 78 ng/L; P = .006), and for
      the astroglial injury marker glial fibrillary acidic protein (mean +/- SD, 541 +/
      199 ng/L vs 405 +/- 138 ng/L; P = .003). The increase was significantly higher
      among boxers who had received many hits (>15) or high-impact hits to the head
      compared with boxers who reported few hits. In the boxers, concentrations of
      neurofilament light protein and glial fibrillary acidic protein, but not total
      tau, were significantly elevated after a bout compared with the nonathletic
      control subjects. With the exception of neurofilament light protein, there were
      no significant differences between boxers after 3 months of rest from boxing and
      the nonathletic control subjects. CONCLUSIONS: Amateur boxing is associated with
      acute neuronal and astroglial injury. If verified in longitudinal studies with
      extensive follow-up regarding the clinical outcome, analyses of cerebrospinal
      fluid may provide a scientific basis for medical counseling of athletes after
      boxing or head injury.

PMID- 16966506
TI  - Regional effects of lamotrigine on cerebral glucose metabolism in idiopathic
      generalized epilepsy.
AB  - BACKGROUND: Antiepileptic drugs have been reported to affect cerebral metabolism.
      We performed (18)F-fluorodeoxyglucose positron emission tomography (PET) before
      and after lamotrigine administration to investigate its effects on cerebral
      glucose metabolism in patients with drug-naive idiopathic generalized epilepsy.
      DESIGN: We included patients who were newly diagnosed as having idiopathic
      generalized epilepsy or who had not taken an antiepileptic drug after the
      diagnosis was made. Antiepileptic drug (18)F-fluorodeoxyglucose PETs were
      obtained before and after lamotrigine administration in 21 subjects (male-female
      ratio, 10:11; mean +/- SD age, 24.3 +/- 2.8 years). The mean lamotrigine dosage
      was 211.9 mg/d (range, 175.0-275.0 mg/d). For statistical parametric mapping
      analysis, all PET images were spatially normalized to the standard PET template
      and then smoothed using a 14-mm full width at half-maximum gaussian kernel. The
      paired t test was used to compare premedication and postmedication (18)F
      fluorodeoxyglucoae PET images. RESULTS: After lamotrigine administration,
      cerebral metabolism was decreased in bilateral thalami, bilateral caudate nuclei,
      the left side of the putamen, the left entorhinal area, bilateral parahippocampal
      gyri, the right inferior temporal gyrus, the left rectosubcallosal gyrus,
      bilateral superior frontal gyri, the left middle frontal gyrus, the right
      precentral gyrus, left pericentral gyri, the right superior parietal lobule, and
      bilateral substantia nigra at P<.05 corrected for multiple comparisons using the
      false discovery rate approach. No brain region showed increased metabolism after
      lamotrigine administration. CONCLUSION: This study revealed that lamotrigine
      treatment reduces glucose metabolism in the thalamus, basal ganglia, and multiple
      regions of the cerebral cortex in drug-naive patients with idiopathic generalized
      epilepsy.

PMID- 16966507
TI  - Distribution and outcome of symptomatic stenoses and occlusions in patients with
      acute cerebral ischemia.
AB  - OBJECTIVE: To describe the distribution of steno-occlusive disease and the
      associated rate of recurrence in patients with acute cerebral ischemia. DESIGN:
      An inception cohort was prospectively recruited after an index event and followed
      up to assess recurrent stroke and death up to 1 year after the event. SETTING:
      Eleven German departments of neurology with acute stroke units. PATIENTS: A total
      of 4157 patients who experienced an acute ischemic stroke or a transient ischemic
      attack and had complete cerebrovascular examination results. Follow-up
      information could be obtained in 85.3% of these patients. RESULTS: Symptomatic
      vessel occlusions were associated with a high mortality rate and were found most
      often in the proximal internal carotid artery (6.5% of patients), the M1 segment
      of the middle cerebral artery (3.7%), and the vertebral artery (3.0%).
      Symptomatic stenosis of 50% to 99% of the internal carotid artery was found in
      308 patients (7.4%), and 272 patients (6.5%) had symptomatic intracranial
      stenosis. The highest rates of recurrent stroke during the first 3 days occurred
      in patients with symptomatic carotid and intracranial occlusions. Overall, 82
      (8.0%) of 1027 patients with symptomatic cerebrovascular disease experienced a
      recurrent stroke between day 4 and 1 year, but no significant differences in
      recurrent stroke rates could be found when comparing different locations of steno
      occlusive disease. CONCLUSIONS: Our study provides representative data on the
      distribution and outcome of steno-occlusive disease in patients with acute
      cerebral ischemia. In contrast to prior studies in more selected populations, the
      rate of recurrent stroke in patients with symptomatic intracranial stenosis was
      not elevated compared with that of patients without steno-occlusive disease.

PMID- 16966508
TI  - Potential for interferon beta-induced serum antibodies in multiple sclerosis to
      inhibit endogenous interferon-regulated chemokine/cytokine responses within the
      central nervous system.
AB  - BACKGROUND: A proportion of patients with multiple sclerosis (MS) receiving
      systemic interferon beta therapy will develop serum neutralizing antibodies
      (NAbs) that can reduce the activity of the drug. Interferon-beta (IFN-beta) is
      produced by glial cells within the central nervous system. Although systemic
      interferon beta does not access the central nervous system, titers of serum NAbs
      may be sufficient that some will access the central nervous system. OBJECTIVE: To
      address whether serum samples that contain high titers of NAbs could inhibit
      glial cell production of chemokines and cytokines that are regulated by
      endogenous IFN-beta. DESIGN: We used an in vitro assay involving toll-like
      receptor 3 ligand (polyinosinic-polycytidylic acid) signaling to assess the
      effect of serum samples containing high titers of NAbs (1800-20 000 U) on
      production of the chemokine CXCL10 and the cytokine interleukin 6 by human
      astrocytes. RESULTS: Serum samples positive for NAbs significantly inhibited
      polyinosinic-polycytidylic acid-induced CXCL10 and IL-6 production by astrocytes.
      CONCLUSION: High-titer NAbs to interferon beta may block endogenous IFN-beta
      function and alter the chemokine/cytokine microenvironment within the central
      nervous system, thereby modulating the profile and course of the local
      inflammatory response.

PMID- 16966509
TI  - Neocortical atrophy, third ventricular width, and cognitive dysfunction in
      multiple sclerosis.
AB  - BACKGROUND: Cognitive dysfunction is common in multiple sclerosis (MS).
      Correlations are reported between atrophy and neuropsychological test results.
      OBJECTIVE: To determine if neocortical volume would supplant or supplement third
      ventricular width and other magnetic resonance imaging measures when predicting
      neuropsychological impairment. DESIGN: Cross-sectional study. SETTING: University
      MS clinic. PARTICIPANTS: Seventy-seven patients with relapsing-remitting MS, 42
      patients with secondary progressive MS, and 27 healthy control subjects. MAIN
      OUTCOME MEASURES: Brain atrophy and lesion burden measures were obtained in all
      patients. A subset of 82 patients and all controls underwent neuropsychological
      testing. RESULTS: Patients with secondary progressive MS had more atrophy than
      patients with relapsing-remitting MS and controls. Neocortical volume was
      significantly correlated with all neuropsychological measures, with r values
      ranging from 0.29 to 0.58. Third ventricular width was retained in most stepwise
      regression analyses predicting cognitive impairment in patients with MS and
      distinguishing secondary progressive from relapsing-remitting courses of MS.
      CONCLUSIONS: We confirm an association between neocortical volume and multiple
      cognitive domains in MS, although neocortical volume did not explain
      significantly more variance than other magnetic resonance imaging measures. Of
      the magnetic resonance imaging variables studied, third ventricular width was
      retained in most regression models.

PMID- 16966510
TI  - Early-onset Alzheimer disease in families with late-onset Alzheimer disease: a
      potential important subtype of familial Alzheimer disease.
AB  - BACKGROUND: Genetic influences on the development of late-onset Alzheimer disease
      (LOAD) are heterogeneous and ill defined. OBJECTIVE: To determine the genetic
      risk factors for LOAD. DESIGN: We asked the following questions: (1) Does early
      onset Alzheimer disease (EOAD) occur in families with predominantly LOAD? and (2)
      Does the apolipoprotein E (APOE) genotype explain the wide differences in onset
      age in LOAD families? SETTING: University of Washington Alzheimer Disease
      Research Center, Seattle. PARTICIPANTS: A total of 136 kindreds and a separate
      group of 29 affected parent-child pairs. MAIN OUTCOME MEASURES: We evaluated the
      kindreds with familial LOAD for the occurrence of EOAD and the affected parent
      child pairs with a 20-year or more difference in the age at onset. RESULTS: In
      the 136 kindreds with LOAD, 104 had only late-onset cases (men, 36%), whereas 32
      families (24%) had a combination of LOAD and EOAD cases. The 44 EOAD cases in
      these families accounted for 20% of cases of AD in the 32 families and 6% in all
      136 families. The early-onset cases had a mean +/- SD onset age of 56.1 +/- 3.2
      years (range, 45-59 years; men, 50%). Seven (28%) of 25 individuals with EOAD
      sampled did not have an APOE epsilon4 allele, and 2 of the earliest-onset cases
      were epsilon3/epsilon3. In 29 parent-child pairs with a 20-year or more
      difference in age at onset, 7 (35%) of the 20 children sampled did not have an
      APOE epsilon4 allele. CONCLUSIONS: Many LOAD families (approximately 25%) have at
      least 1 individual with EOAD, and in these individuals, the ratio of men to women
      is nearly 50%, suggesting a possible subtype of familial AD. The APOE genotype
      plays an important role in these early-onset cases, but at least one fourth of
      the risk must represent the influence of other genetic and/or environmental
      factors. These LOAD families with early-onset cases represent an important
      resource for investigation of these factors.

PMID- 16966511
TI  - Accelerated weight loss may precede diagnosis in Alzheimer disease.
AB  - OBJECTIVES: To determine the association of weight loss and the onset of dementia
      of the Alzheimer type (DAT) and to characterize the rate of weight change over
      time in older adults (aged 65-95 years) who develop DAT vs those who remain
      without dementia. DESIGN: Rates of weight change were investigated in older adult
      research participants (N = 449) who were enrolled as control subjects without
      dementia and followed up longitudinally (6 years on average) at the Alzheimer's
      Disease Research Center, Washington University School of Medicine. Some
      individuals (n = 125) eventually developed DAT; the others (n = 324) remained
      without dementia. Body weight was measured at each annual assessment. Piecewise
      linear regression and random effects models were used to test longitudinal rates
      of weight change between the groups. RESULTS: Participants without dementia lost
      about 0.6 lb per year. For those individuals who developed DAT, about 1 year
      before the detection of DAT, the rate of weight loss doubled (1.2 lb per year).
      As a group, participants who eventually developed DAT weighed less (about 8
      pounds) at study enrollment (ie, when they did not have dementia) than
      participants who remained without dementia. CONCLUSIONS: Aging with and without
      DAT is associated with weight loss; however, weight loss may accelerate before
      the diagnosis of DAT. Specific factors contributing to weight loss are unknown,
      but these data suggest they operate before the development of DAT. Hence, weight
      loss may be a preclinical indicator of Alzheimer disease.

PMID- 16966513
TI  - Generalized epilepsy and classic spike-wave discharges with unilateral thalamic
      lesions.
AB  - BACKGROUND: Idiopathic generalized epilepsy (IGE) is a heterogeneous condition
      with a predominantly genetic origin. Clinical hallmarks of IGE syndromes include
      generalized spike and wave discharges and normal results on brain imaging.
      OBJECTIVE: To describe 2 patients with clinical presentations compatible with IGE
      but whose imaging studies revealed unilateral thalamic lesions. DESIGN: Case
      reports. SETTING: University-affiliated hospitals. PATIENTS: Two 21-year-old
      patients (1 man and 1 woman). MAIN OUTCOME MEASURES: Magnetic resonance imaging
      findings. RESULTS: Magnetic resonance imaging unexpectedly revealed unilateral
      thalamic lesions. CONCLUSIONS: We recommend doing magnetic resonance imaging
      studies in patients with IGE, especially in refractory or atypical cases. In rare
      cases, clinical features compatible with IGE may be associated with structural
      thalamic or other lesions.

PMID- 16966512
TI  - Combined antiviral-immunosuppressive treatment in human T-lymphotrophic virus 1
      Sjogren-associated myelopathy.
AB  - BACKGROUND: In several studies, antiretroviral drugs (principally zidovudine)
      have been used with success in the treatment of myelopathy associated with human
      T-lymphotrophic virus 1 (HTLV-1) (tropical spastic paraparesis-HTLV-1-associated
      myelopathy). The retrovirus HTLV-1 has been implicated as a causative agent of
      Sjogren syndrome (SS) in clinical reports and murine experiments. Moreover, a
      recognized complication of primary SS is a myelopathy, which has been shown in
      case reports to respond to immunosuppressive treatment. OBJECTIVE: To describe a
      patient with a rapidly progressive, extensive myelopathy with evidence of HTLV-1
      infection and SS (probably secondary to HTLV-1) in whom we achieved spectacular
      therapeutic success using combined immunosuppressive and antiviral therapy.
      DESIGN: Case report. SETTING: University hospital. Patient A young Haitian woman
      diagnosed with HTLV-1 and SS developed extensive myelopathy leading to severe
      disability. MAIN OUTCOME MEASURES: Clinical and radiological improvement.
      RESULTS: Spectacular radiological and clinical recovery as well as stabilization
      were achieved with combined antiviral and immunosuppressant treatment. Follow-up
      at 2 years showed no signs of relapse. CONCLUSIONS: Both tropical spastic
      paraparesis-HTLV-1-associated myelopathy and Sjogren myelopathy are potentially
      very disabling. Rapidly progressive myelopathy secondary to SS necessitates the
      introduction of immunosuppressant therapies. The presence of HTLV-1 may confer
      the necessity to add antiviral therapy.

PMID- 16966514
TI  - Opsoclonus persisting during sleep in West Nile encephalitis.
AB  - BACKGROUND: Recent outbreaks of West Nile virus infection have alerted the public
      to disabling paralysis as an outcome. Ocular motor involvement with West Nile
      virus is rare. OBJECTIVE: To describe a patient with West Nile virus encephalitis
      that resulted in opsoclonus-myoclonus syndrome with persistent ocular oscillation
      on electroencephalography during stage 2 sleep. PATIENT: A 53-year-old man who
      presented with viral prodrome followed by intense vertigo and encephalopathy. In
      addition to multifocal myoclonic jerks in the extremities, his eye movements were
      disrupted by bursts of high-frequency, conjugate ocular oscillations that
      occurred in random directions. RESULTS: Electroencephalography showed eye
      movement artifacts during the awake state and stage 2 sleep. Opsoclonus-myoclonus
      syndrome remained disabling 3 months after onset but markedly improved 8 months
      after onset. CONCLUSIONS: West Nile virus is another cause of opsoclonus
      myoclonus syndrome that can occur in conjunction with encephalitis. The presence
      of an eye movement artifact on results of electroencephalography during stage 2
      sleep should raise suspicion for opsoclonus.

PMID- 16966515
TI  - Abdominal pseudohernia caused by herpes zoster truncal D12 radiculoneuropathy.

PMID- 16966516
TI  - Spontaneous improvement of syringomyelia with deterioration of a Chiari type I
      malformation and new symptoms.

PMID- 16966517
TI  - Vertebral artery susceptibility sign as a marker of vertebral thromboembolism on
      magnetic resonance imaging.

PMID- 16966518
TI  - Cerebral sinus thrombosis.

PMID- 16966519
TI  - Transient global amnesia: increasing evidence of a venous etiology.

PMID- 16966520
TI  - Transient global amnesia: the continuing quest for a source.

PMID- 16966521
TI  - Transient global amnesia: look at mechanisms not causes.

PMID- 16966522
TI  - History of the corpus luysii: 1865-1995.

PMID- 16966523
TI  - Dopamine receptor agonists and levodopa and inducing psychosis-like behavior in
      the MPTP primate model of Parkinson disease.

PMID- 16966524
TI  - Interhemispheric dissociation of language regions in a healthy subject.

PMID- 16966525
TI  - LRRK2 gene and tremor-dominant parkinsonism.

PMID- 16966526
TI  - Benign tremulous parkinsonism.

PMID- 16966527
TI  - Stroke and memory decline: a question of degenerative or vascular origin.

PMID- 16966528
TI  - Brainstem activity in migraine: primary or secondary?

PMID- 16966529
TI  - Neuro-ophthalmology Internet digital media library.

PMID- 16966530
TI  - NIPPV: a treatment for ALS whose time has come.

PMID- 16966531
TI  - Susceptibility genes in sporadic ALS: separating the wheat from the chaff by
      international collaboration.

PMID- 16966532
TI  - There is nothing staid about STARD: progress in the reporting of diagnostic
      accuracy studies.

PMID- 16966533
TI  - Update on the pharmacology of REM sleep behavior disorder.
AB  - REM sleep behavior disorder (RBD) is characterized by complex behavioral
      manifestations in response to dream content that may cause sleep disruption or
      injuries to the patient or the bed partner. In this case, the patients need
      treatment to control their symptoms. Pharmacologic agents have been reported to
      have positive and negative impacts on REM sleep muscle atonia and the motor
      behaviors associated with RBD. Clonazepam is efficacious and well tolerated by
      the majority of patients afflicted by RBD and should be considered as initial
      treatment. In patients at risk of falls who have cognitive impairment or who have
      obstructive sleep apneas, melatonin may be a good alternative to clonazepam.
      Anticholinesterase inhibitors and dopaminergic agents are not of clear benefit.
      Monoamine oxidase inhibitors, tricyclic antidepressants, serotonergic synaptic
      reuptake inhibitors, and noradrenergic antagonists can induce or aggravate RBD
      symptoms and should be avoided in patients with RBD. When these agents are
      prescribed to patients with neurodegenerative disorders or narcolepsy who are at
      risk of developing RBD, systematic follow-up may be warranted to detect the
      emergence of RBD symptoms.

PMID- 16966534
TI  - Effects of rivastigmine on cognitive function in patients with traumatic brain
      injury.
AB  - OBJECTIVE: To compare the efficacy and safety of rivastigmine (3 to 6 mg/day) vs
      placebo over 12 weeks in patients with traumatic brain injury and persistent
      cognitive impairment. METHODS: This prospective, randomized, double-blind,
      placebo-controlled study was conducted in 157 patients at least 12 months after
      injury. The primary efficacy measures were the Cambridge Neuropsychological Test
      Automated Battery (CANTAB) Rapid Visual Information Processing (RVIP) A' subtest
      and the Hopkins Verbal Learning Test (HVLT). The primary efficacy outcome was the
      proportion of patients who demonstrated 1.0 SD or greater improvement from
      baseline at week 12 on CANTAB RVIP A' or HVLT. RESULTS: The percentage of
      responders at week 12 on either the CANTAB RVIP A' or HVLT was 48.7% for
      rivastigmine and 49.3% for placebo (p = 0.940). Furthermore, for the overall
      study population, there were no significant differences for any of the secondary
      efficacy variables. In a subgroup of patients with moderate to severe memory
      impairment (n = 81), defined as 25% impairment or greater on HVLT at baseline,
      rivastigmine was significantly better than placebo for a number of measures,
      including the proportion of HVLT responders and CANTAB RVIP mean latency.
      CONCLUSIONS: Rivastigmine was safe and well tolerated in patients with traumatic
      brain injury with cognitive deficits. Rivastigmine shows promising results in the
      subgroup of patients with traumatic brain injury with moderate to severe memory
      deficits.

PMID- 16966535
TI  - Hippocampal volume, brain atrophy, and APOE genotype after traumatic brain
      injury.
AB  - OBJECTIVE: To examine the association between hippocampal volumes, general brain
      atrophy, and apolipoprotein E (APOE) polymorphism in patients with a remote
      traumatic brain injury (TBI). METHODS: MRI-based volumetric analyses of the
      hippocampus and lateral ventricles were performed in 58 patients with TBI of
      varying severity on average 31.3 years after the trauma. The APOE genotype was
      determined using standard methods and correlated with the MRI volumetric
      measurements. RESULTS: Hippocampal or lateral ventricle volumes did not differ
      significantly in those patients with the APOE-epsilon4 allele (APOE4) vs those
      without this allele. CONCLUSIONS: The APOE-epsilon4 allele was not associated
      with the development of hippocampal or ventricular atrophy after traumatic brain
      injury. If the APOE-epsilon4 allele is associated with an unfavorable outcome
      after traumatic brain injury as proposed, this association may involve mechanisms
      other than those responsible for the development of brain atrophy.

PMID- 16966536
TI  - Trends in hospital utilization and outcome for patients with ALS: analysis of a
      large U.S. cohort.
AB  - OBJECTIVE: To examine hospital mortality, utilization, and trends in care of
      patients with ALS in a large U.S. cohort. METHODS: The authors performed a
      retrospective cohort comparison, using the Nationwide Inpatient Sample for 1988
      to 2002. They identified admissions, comorbidities, and procedures using ICD-9
      codes. Outcomes included reason for admission, cost (adjusted to 2002 dollars),
      length of stay, discharge disposition, and utilization of hospice care.
      Significance was set a priori at p < 0.001. RESULTS: They identified 17,249
      records. The significant findings were that common morbidities increased over
      time (pneumonia [38.1% to 47.3%], respiratory failure [26.9% to 35.5%], and
      nutritional deficiency [43.0% to 56.3%]); the median length of stay dropped from
      6 to 4 days; mean hospital charges increased from 21,574 dollars to 24,314
      dollars; the proportion of hospital deaths decreased over time (17.6% to 14.6%),
      whereas the proportion discharged to home health/hospice care (14.0% to 18.2%)
      and to long-term care facilities (13.2% to 27.9%) increased. The odds ratio (OR)
      of death was 5.03 (95% CI: 4.57 to 5.54) for those admitted with respiratory
      failure, 1.36 (1.24 to 1.50) for those with pneumonia, and 0.84 (0.77 to 0.92)
      for those with nutritional deficiency. CONCLUSION: The high OR of death in
      patients admitted for pneumonia or respiratory failure is likely associated with
      more advanced disease, whereas the protective effect of admission for nutritional
      deficiency is consistent with the predominance of bulbar symptoms and admission
      earlier in the disease. The trends during the 15 years of this administrative
      data set were for increasing comorbidities and higher utilization of end-of-life
      care.

PMID- 16966537
TI  - Peripheral neurotoxicity of pegylated interferon alpha: a prospective study in
      patients with HCV.
AB  - OBJECTIVE: To assess whether pegylated interferon alpha (PEG-IFNalpha) may induce
      peripheral neuropathy or antibodies to peripheral nerve antigens in patients with
      hepatitis C virus (HCV) infection. METHODS: We studied 52 patients with HCV (38
      men, 14 women; mean age 44.6 +/- 10.6 years) treated with IFNalpha. Before
      therapy (T(0)), patients underwent quantitative viral RNA determination, HCV
      genotype analysis, and neurologic and electrophysiologic evaluation. At the end
      (T(1)) and after therapy (T(2)), patients were neurologically and
      electrophysiologically re-evaluated. Antibodies to gangliosides and sulfatides
      were assayed by ELISA at T(0) and T(1). Twenty-three patients with HCV with
      comparable age, viral load, and genotype, not treated with IFNalpha, were studied
      as controls. RESULTS: Seven patients (six in IFNalpha, one control) had
      peripheral neuropathy at recruitment. No significant differences in the
      electrophysiologic measures were detected between T(0) and T(1) (repeated
      measures analysis of variance [ANOVA]) in any of the 52 patients or in those with
      neuropathy at T(0). No changes were found at T(2), independent of the viral
      response to treatment. Two patients, one with neuropathy, had antiganglioside
      antibodies at recruitment. Two patients, one not treated with IFNalpha, developed
      low antibody titers during follow-up, without symptoms or signs of neuropathy.
      CONCLUSIONS: Pegylated interferon alpha therapy was not associated with the
      occurrence (or worsening) of peripheral neuropathy or antibodies to peripheral
      nerve antigens in patients with hepatitis C virus.

PMID- 16966538
TI  - Pain and small-fiber neuropathy in patients with hypothyroidism.
AB  - OBJECTIVE: To investigate large- and small-fiber function in patients with
      hypothyroidism and pain. METHODS: The authors studied 38 women treated for
      hypothyroidism and with painful extremities and 38 healthy controls. All subjects
      underwent neurologic examination of the extremities, neurophysiologic testing of
      large myelinated nerves, and thresholds for warmth detection (WDT), cold
      detection (CDT), heat-pain detection (HPDT), and cold-pain detection (CPDT) in
      one upper and both lower limbs. RESULTS: Eighteen patients had ongoing or
      intermittent ongoing distal pain in their limbs. Of these, 8 reported evoked and
      10 reported paroxysmal pain. Fifteen patients had only diffuse musculoskeletal
      pain. A total of 16 patients had "hyperphenomena" (brush-evoked allodynia,
      punctate hyperalgesia, or cold allodynia or a combination of these, in their feet
      or hands or both). Eight patients were classified as having large fiber
      neuropathy, whereas 20 had "hypophenomena" (elevated thermal thresholds in their
      feet or hands or both). Thermal thresholds at the feet (WDT, CDT, and HPDT) were
      elevated (p = 0.001, p = 0.007, and p = 0.003, respectively) in the whole group
      of patients compared with the controls as well as WDT (p = 0.001) and CDT (p =
      0.001) being elevated at the thenar eminence. All patients with ongoing, evoked,
      or paroxysmal pain had either hyperphenomena or hypophenomena or a combination of
      the two. CONCLUSIONS: Some patients treated for hypothyroidism have symptoms and
      findings compatible with small-fiber neuropathy or "hyperphenomena" indicating
      central sensitization.

PMID- 16966539
TI  - The quality of diagnostic accuracy studies since the STARD statement: has it
      improved?
AB  - OBJECTIVE: To assess whether the quality of reporting of diagnostic accuracy
      studies has improved since the publication of the Standards for the Reporting of
      Diagnostic Accuracy studies (STARD statement). METHODS: The quality of reporting
      of diagnostic accuracy studies published in 12 medical journals in 2000 (pre
      STARD) and 2004 (post-STARD) was evaluated by two reviewers independently. For
      each article, the number of reported STARD items was counted (range 0 to 25).
      Differences in completeness of reporting between articles published in 2000 and
      2004 were analyzed, using multilevel analyses. RESULTS: We included 124 articles
      published in 2000 and 141 articles published in 2004. Mean number of reported
      STARD items was 11.9 (range 3.5 to 19.5) in 2000 and 13.6 (range 4.0 to 21.0) in
      2004, an increase of 1.81 items (95% CI: 0.61 to 3.01). Articles published in
      2004 reported the following significantly more often: methods for calculating
      test reproducibility of the index test (16% vs 35%); distribution of the severity
      of disease and other diagnoses (23% vs 53%); estimates of variability of
      diagnostic accuracy between subgroups (39% vs 60%); and a flow diagram (2% vs
      12%). CONCLUSIONS: The quality of reporting of diagnostic accuracy studies has
      improved slightly over time, without a more pronounced effect in journals that
      adopted the STARD statement. As there is still room for improvement, editors
      should mention the use of the STARD statement as a requirement in their
      guidelines for authors, and instruct reviewers to check the STARD items. Authors
      should include a flow diagram in their manuscript.

PMID- 16966540
TI  - Lifetime prevalence and concordance risk of cluster headache in the Swedish twin
      population.
AB  - OBJECTIVE: To examine the lifetime prevalence and the concordance risk of cluster
      headache (CH) in a twin sample representative of the Swedish general population.
      METHODS: The authors assessed CH as defined by the second edition of the
      International Classification of Headache Disorders in 31,750 registered twins
      born from 1935 to 1958. Structured lay screening interviews were followed by
      neurologist interviews of possible cases. Co-twins of affected index twins were
      follow-up interviewed regardless of their screening outcome. RESULTS: A total of
      250 screening-positives (0.8%) were found, of which 218 (88%) were follow-up
      interviewed. Forty-five (21%) had the CH diagnosis verified. Among screen
      negatives, hospitalization records pointed at two more verified cases and index
      twins at one more verified case. A total of 48 CH cases provided a crude lifetime
      prevalence of 151 per 100,000 (95% CI: 108, 194). The male-to-female sex ratio
      corresponded to 4.8 (95% CI: 2.3, 9.9). The crude lifetime prevalence of CH was
      higher in the twins born from 1945 to 1958 than in the twins born from 1935 to
      1944 (190 vs 90/100,000). CH recurred in 2 of 12 co-twins of monozygous index
      twins (including 1 nonparticipant twin), whereas all co-twins of 25 dizygous
      index twins proved to be unaffected. CONCLUSION: As many as 1 per 500 of the
      general population are affected by cluster headache. Twin concordance seems low,
      but genetic factors may play a role for familial clustering.

PMID- 16966541
TI  - Relapses and subsequent worsening of disability in relapsing-remitting multiple
      sclerosis.
AB  - OBJECTIVE: To investigate whether relapses contribute to the development of
      subsequent sustained increase of impairment and disability in patients with
      multiple sclerosis (MS). METHODS: In a random sampled subset of 256 relapsing
      remitting MS (RRMS) patients from the placebo arms of 20 randomized, controlled
      clinical trials contained in the Sylvia Lawry Centre for MS Research (SLCMSR)
      open database (mean follow-up time 2.66 years), the authors tested whether time
      to an increase of the Expanded Disability Status Scale (EDSS) score (confirmed
      after 6 months) was related to the occurrence of prior relapses. In the primary
      analysis, EDSS progressions starting within the period used to calculate the on
      study relapse rate (sacrifice period) were not counted. The result obtained was
      then validated in an independent validation part of the SLCMSR database (n =
      320). RESULTS: Although in the first subset of 256 RRMS patients, occurrence of
      relapses in the first 4 months on study appeared to be the best predictor for a
      shorter time to subsequent sustained increase in the EDSS score (hazard ratio
      [HR] 2.26 [95% CI: 1.36 to 3.75]), this finding was not confirmed in the
      validation dataset (HR 1.35, one-sided Wald test, lower limit of the 95% CI:
      0.90). CONCLUSION: Although relapses may result into permanent damage and
      Expanded Disability Status Scale (EDSS) progression, there is no consistent
      effect of on-study relapses on the subsequent development of sustained EDSS score
      increase during a typical clinical study observation period.

PMID- 16966542
TI  - Are initial demyelinating event recovery and time to second event under
      differential control?
AB  - BACKGROUND: Relapsing-remitting multiple sclerosis (RRMS) begins with an initial
      demyelinating event (IDE) that can be monosymptomatic, polysymptomatic, or
      polyregional. Failure to recover from the IDE is a known predictor of later
      development of disability. Factors that predict IDE recovery (outside optic
      neuritis) and time to second event are relatively unknown. The authors speculate
      that IDE recovery and time to second event are under separate biologic or genetic
      control, and as such, their clinical predictors are different. METHODS: Data on
      all UCSF MS clinic patients are entered prospectively into an ACCESS database.
      The authors identified all patients seen at the UCSF clinic within 1 year of
      their IDE. Expanded Disability Status Scale scores, functional system scores, and
      visual acuity were used to define IDE severity and recovery. RESULTS: The cohort
      included 186 patients (127 women, 59 men) with an average onset age of 34 +/- 10
      years with 150 whites (non-Hispanic), 15 African Americans, 11 Hispanics, eight
      Asians, and two unknown/unreported. Worse onset severity predicted worse IDE
      recovery (23.1% of the patients with severe onset vs 32.9% with moderate severity
      vs 56.4% with mild onset recovered completely, p < 0.001). Polyregional onset
      predicted poor recovery compared to monoregional onset (46.2% vs 14.4%, p <
      0.001). Nonwhite patients were 2.48 times more likely than whites to experience a
      second episode within 1 year from onset (95% CI: 1.45 to 4.23, p < 0.001).
      Similarly, age younger than 30 years predicted higher risk of a second
      exacerbation (hazard ratio 1.92, 95% CI: 1.17 to 3.15, p = 0.010). CONCLUSION:
      Initial demyelinating event recovery and time to second event may have distinct
      predictors. These findings suggest that recovery and time to second event might
      be under separate biologic control.

PMID- 16966543
TI  - Cerebral venous sinus thrombosis: Incidence of venous thrombosis recurrence and
      survival.
AB  - OBJECTIVE: To determine whether treatments guidelines for lower extremity venous
      thrombosis (DVT) could be applied to patients with cerebral venous sinus
      thrombosis (CVST), the rates of recurrent venous thrombosis and survival for
      these two diseases were compared. METHODS: The authors studied all patients
      diagnosed with CVST at the Mayo Clinic between 1978 and 2001. Survival and
      recurrent venous thrombosis rates (cerebral or noncerebral) were compared with
      those from patients with DVT. Survival rates were also compared with white US
      residents. RESULTS: One hundred fifty-four patients (age 40 +/- 19 years) were
      included (58% women). Warfarin, prescribed in 50% of patients, was continued for
      an average of 9 months. During a mean of follow up of 36 +/- 47 months (464
      patient-years), 20 patients experienced 23 recurrent venous thrombi for an event
      rate of 5.0/100 patient-years. This recurrence rate was similar to patients with
      lower extremity DVT (3.8/100 patient-years). Mortality rates were lower for CVST
      (2.8/100 patient-years) compared with DVT (6.2/100 patient-years; p = 0.001)
      patients but higher than expected for white US residents (p = 0.001). Increasing
      age and active malignancy were the only predictors of poor survival. Neither
      recurrent thrombosis nor survival was influenced by warfarin therapy.
      CONCLUSIONS: The likelihood of recurrent venous thrombosis is similar after
      cerebral venous sinus thrombosis (CVST) and lower extremity deep venous
      thrombosis (DVT). Compared with DVT, survival rates are higher following CVST but
      are adversely influenced by malignancy and older age.

PMID- 16966544
TI  - Blood pressure measures and risk of total, ischemic, and hemorrhagic stroke in
      men.
AB  - OBJECTIVE: To evaluate which blood pressure measure is the best predictor of risk
      of total, ischemic, and hemorrhagic stroke. METHODS: The authors used a
      prospective cohort study among 11,466 men followed for incident stroke during a
      median of 19.4 years in the Physicians' Health Study. Systolic blood pressure
      (SBP) and diastolic blood pressure (DBP) were self-reported. They calculated
      relative risks (RRs) and 95% CIs for total, ischemic, and hemorrhagic stroke
      using Cox proportional hazards models. Model fit was compared using the chi(2)
      test statistic from likelihood ratio tests. RESULTS: During follow-up, 508
      strokes occurred (411 ischemic, 89 hemorrhagic, and eight of unknown etiology).
      For each 10-mm Hg increase in SBP, the multivariable RRs were 1.31 (95% CI: 1.20
      to 1.42) for total stroke, 1.28 (95% CI: 1.16 to 1.40) for ischemic stroke, and
      1.38 (95% CI: 1.13 to 1.68) for hemorrhagic stroke. Although DBP, pulse pressure,
      and mean arterial pressure were all significant predictors of stroke risk, none
      was a significantly better predictor than SBP alone. Adding DBP did not
      significantly improve the model fit of SBP alone for any stroke type. CONCLUSION:
      In this large cohort of initially healthy men, systolic blood pressure was a
      consistent and significant predictor of total, ischemic, and hemorrhagic stroke.
      Systolic blood pressure alone was the only measure necessary to predict risk of
      total stroke or its major subtypes.

PMID- 16966545
TI  - How affected is oxygen metabolism in DWI lesions?: A combined acute stroke PET-MR
      study.
AB  - OBJECTIVE: To use back-to-back diffusion-weighted imaging (DWI) and PET to obtain
      quantitative measures of the cerebral metabolic rate of oxygen (CMRO(2)) within
      DWI lesions, and to assess the perfusion-metabolism coupling status by measuring
      the cerebral blood flow and the oxygen extraction fraction within DWI lesions.
      METHODS: Six prospectively recruited acute carotid-territory stroke patients
      completed the imaging protocol, which was commenced 7 to 21 hours from onset and
      combined DWI derived from state-of-the-art diffusion tensor imaging sequencing
      using a 3-T magnet and fully quantitative (15)O-PET. The PET variables were
      obtained in individual DWI lesions in each patient. RESULTS: Across patients, the
      CMRO(2) was reduced in the DWI lesion relative to mirror (mean reduction 39.5%; p
      = 0.028). Examining individual DWI lesions, however, revealed considerable
      variability in the extent of this CMRO(2) reduction. The flow-metabolism coupling
      pattern underlying the DWI lesion was also variable, including ongoing ischemia,
      mild oligemia, and partial or complete reperfusion. DISCUSSION: Diffusion
      weighted imaging (DWI) lesions generally reflect substantial disruption of energy
      metabolism. However, the degree of metabolic disruption is variable, indicating
      DWI lesions may not always represent irreversibly damaged tissue. Finally,
      because DWI lesions can persist despite reperfusion, assessment of perfusion is
      necessary for interpretation of DWI changes in acute stroke.

PMID- 16966546
TI  - Associations between white matter lesions, cerebrovascular risk factors, and low
      CSF Abeta42.
AB  - OBJECTIVE: To analyze a putative relationship between white matter lesions
      (WMLs), risk factors for WMLs, and Alzheimer disease (AD) as measured with the
      surrogate marker CSF Abeta42. METHODS: The authors analyzed effects of acquired
      risk factors for cerebrovascular disease and WMLs on AD as measured with an
      intermediate marker, CSF Abeta42. A total of 127 consecutive patients with
      subjective memory impairment (mean age 66 years; 57 women) investigated at a
      university-based memory clinic had brain MRI scans. WMLs were rated on a 12-point
      scale with a semiquantitative procedure. They used path analysis with established
      and possible risk factors for WMLs and for reduced CSF Abeta42 (age,
      hypertension, hyperhomocysteinemia, hypercholesterolemia, APOE-epsilon4) as
      variables. RESULTS: The WML score was 1.5 points higher (p < 0.05) in
      hypertensive than in nonhypertensive patients and 1.9 points higher (p < 0.05) in
      patients with hyperhomocysteinemia than in those with normal homocysteine levels.
      Hypercholesterolemia increased the probability of low CSF Abeta42 levels by 0.2
      (p < 0.05). For each point increase in WML score, the probability of low CSF
      Abeta42 levels increased by 0.03 (p < 0.05). APOE-epsilon4 was associated with
      reduced CSF Abeta42 (p < 0.01). CONCLUSION: Both hypercholesterolemia and white
      matter lesions may contribute to low CSF Abeta42 by independent mechanisms.

PMID- 16966548
TI  - Association of metabolic syndrome with Alzheimer disease: a population-based
      study.
AB  - OBJECTIVE: To assess the association of metabolic syndrome (MetS) with Alzheimer
      disease (AD). METHODS: The authors derived subjects from a population-based study
      of 980 randomly selected elderly subjects. After exclusion of all non-Alzheimer
      dementia cases, the final study population included 959 subjects (337 men and 622
      women) aged 69 to 78 years. The presence of MetS was defined according to the
      National Cholesterol Education Program (Adult Treatment Panel III) criteria, and
      the diagnosis of AD was based on the criteria of the National Institute of
      Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and
      Related Disorders Association. RESULTS: Of the study subjects, 418 (43.6%) had
      MetS. Probable or possible AD was diagnosed in 45 subjects (4.7%). AD was more
      frequently detected in subjects with MetS than in subjects without MetS (7.2 vs
      2.8%; p < 0.001). The prevalence of AD was higher in women with MetS vs women
      without the syndrome (8.3 vs 1.9%; p < 0.001), but in men with MetS, the
      prevalence of AD was not increased (3.8 vs 3.9%; p = 0.994). In univariate
      logistic regression analysis, MetS was significantly associated with AD (odds
      ratio [OR] 2.71; 95% CI 1.44 to 5.10). In multivariate logistic regression
      analysis including also apolipoprotein E4 phenotype, education, age, and total
      cholesterol, MetS was significantly associated with AD (OR 2.46; 95% CI 1.27 to
      4.78). If only nondiabetic subjects were included in the multivariate analysis,
      MetS was still significantly associated with AD (OR 3.26; 95% CI 1.45 to 7.27).
      CONCLUSION: Metabolic syndrome is associated with Alzheimer disease in elderly
      subjects.

PMID- 16966549
TI  - MRI reveals structural abnormalities in patients with idiopathic generalized
      epilepsy.
AB  - OBJECTIVE: To evaluate MRI findings in a large group of patients with idiopathic
      generalized epilepsies. METHODS: Idiopathic generalized epilepsies were diagnosed
      according to clinical and EEG criteria following International League Against
      Epilepsy recommendations. MRI was performed in a 2.0 T scanner using a previously
      established epilepsy protocol. Images were reviewed, and any abnormality was
      reported. Patients were divided in those with and without MRI abnormalities.
      Comparisons were made between these groups concerning age, age at seizure onset,
      subsyndrome, EEG findings, and seizure control. RESULTS: Of the 134 MRIs
      evaluated, 33 (24%) showed abnormalities, most of which (88%) were nonspecific.
      There were eight main abnormalities: arachnoid cyst, diffuse cortical atrophy,
      basal ganglia abnormalities (signal alterations and prominent perivascular
      spaces), ventricular abnormalities (uni- or bilateral increased volume of the
      lateral ventricles), white matter abnormalities (increased T2 signal in the
      frontal lobes), reduced hippocampal volume, focal gyral abnormality, and area of
      gliosis in the frontal lobe. Comparisons between the groups showed a higher
      proportion of EEG focalities in patients with abnormal MRI, which were in most
      part concordant with the location of the MRI abnormalities. CONCLUSIONS: Twenty
      four percent of patients with idiopathic generalized epilepsies had MRI
      abnormalities. However, the majority of these abnormalities were nonspecific.

PMID- 16966547
TI  - Older adults with cognitive complaints show brain atrophy similar to that of
      amnestic MCI.
AB  - OBJECTIVE: To examine the neural basis of cognitive complaints in healthy older
      adults in the absence of memory impairment and to determine whether there are
      medial temporal lobe (MTL) gray matter (GM) changes as reported in Alzheimer
      disease (AD) and amnestic mild cognitive impairment (MCI). METHODS: Participants
      were 40 euthymic individuals with cognitive complaints (CCs) who had normal
      neuropsychological test performance. The authors compared their structural brain
      MRI scans to those of 40 patients with amnestic MCI and 40 healthy controls (HCs)
      using voxel-based morphometry and hippocampal volume analysis. RESULTS: The CC
      and MCI groups showed similar patterns of decreased GM relative to the HC group
      on whole brain analysis, with differences evident in the MTL, frontotemporal, and
      other neocortical regions. The degree of GM loss was associated with extent of
      both memory complaints and performance deficits. Manually segmented hippocampal
      volumes, adjusted for age and intracranial volume, were significantly reduced
      only in the MCI group, with the CC group showing an intermediate level.
      CONCLUSIONS: Cognitive complaints in older adults may indicate underlying
      neurodegenerative changes even when unaccompanied by deficits on formal testing.
      The cognitive complaint group may represent a pre-mild cognitive impairment stage
      and may provide an earlier therapeutic opportunity than mild cognitive
      impairment. MRI analysis approaches incorporating signal intensity may have
      greater sensitivity in early preclinical stages than volumetric methods.

PMID- 16966550
TI  - Excessive daytime sleepiness in Parkinson disease: is it the drugs or the
      disease?
AB  - OBJECTIVE: To examine associated demographic and clinical correlates and the
      development of excessive daytime sleepiness (EDS) over 8 years in a community
      based cohort of patients with Parkinson disease (PD). METHODS: A total of 232
      patients with PD were included in a population-based prevalence study in 1993.
      Patients were followed prospectively and reexamined after 4 and 8 years. At all
      study visits, the authors administered semistructured interviews to obtain
      information on clinical and demographic variables. Standardized rating scales of
      parkinsonism, depression, and cognitive impairment were used. The diagnosis of
      EDS was based on a sleep questionnaire and in 2001 also on the Epworth Sleepiness
      Scale. Population-averaged logistic regression models for correlated data were
      performed to study the relationship between EDS and various demographic and
      clinical variables. RESULTS: Of the 232 patients included at baseline, 138 were
      available for re-evaluation after 4 years and 89 patients after 8 years.
      Frequency rates of EDS increased from 5.6% in 1993 to 22.5% in 1997 and 40.8% in
      2001, with an 8-year prevalence of 54.2%. In the majority of patients, EDS was a
      persistent feature. In the logistic regression model, EDS was related to age,
      gender, and use of dopamine agonists. In those never having used dopamine
      agonists, hypersomnia was associated with the Hoehn and Yahr stage only.
      CONCLUSION: Excessive daytime sleepiness is a frequent and highly persistent
      feature in Parkinson disease, with multifactorial underlying pathophysiology. The
      authors' findings indicate that both age and disease related disturbances of the
      sleep-wake regulation contribute to hypersomnia in PD. Treatment with dopamine
      agonists also contributed to excessive daytime sleepiness in our patients.

PMID- 16966551
TI  - Late-onset metachromatic leukodystrophy: genotype strongly influences phenotype.
AB  - BACKGROUND: P426L and I179S are the two most frequent mutations in juvenile and
      adult metachromatic leukodystrophy (late-onset MLD), which, in contrast to
      infantile MLD, show marked phenotypic heterogeneity. OBJECTIVE: To search for
      genotype-phenotype correlations in late-onset MLD. METHODS: The authors reviewed
      the clinical course of 22 patients homozygous for mutation P426L vs 20 patients
      heterozygous for mutation I179S, in which the second arylsulfatase A (ASA)
      mutation had also been determined. RESULTS: P426L homozygotes principally
      presented with progressive gait disturbance caused by spastic paraparesis or
      cerebellar ataxia; mental disturbance was absent or insignificant at the onset of
      disease but became more apparent as the disease evolved. In contrast, compound
      heterozygotes for I179S presented with schizophrenia-like behavioral
      abnormalities, social dysfunction, and mental decline, but motor deficits were
      scarce. Reduced peripheral nerve conduction velocities and less residual ASA
      activity were present in P426L homozygotes vs I179S heterozygotes. CONCLUSION:
      The characteristic clinical differences between homozygous P426L and compound
      heterozygous I179S patients establish a distinct genotype-phenotype correlation
      in late-onset metachromatic leukodystrophy.

PMID- 16966552
TI  - Andreas Rett and benign familial neonatal convulsions revisited.
AB  - In 1964 Andreas Rett published the first account of a family with benign familial
      neonatal convulsions (BFNC). The authors retraced Rett's family and report that
      the clinical and genetic features of this original family fit the currently
      accepted definitions of BFNC. They also consider the career of Dr. Rett, a
      researcher and social reformer as well as an advocate for the rights of children
      with developmental disabilities.

PMID- 16966553
TI  - A novel familial MECP2 mutation in a young boy: clinical and molecular findings.
AB  - We describe the clinical and molecular findings of a 6-year-old boy carrying a
      novel missense 964C>T mutation on the MECP2 gene. The patient shows moderate
      mental retardation with autistic features and epilepsy. His mother is
      heterozygous for the same mutation.

PMID- 16966554
TI  - Factors associated with poor compliance of patients with epilepsy driving
      restrictions.
AB  - The authors sought to identify factors associated with poor compliance with
      driving restrictions due to a diagnosis of epilepsy. They compared the
      demographic and clinical characteristics of 60 patients with epilepsy who,
      despite the authors' recommendation, continued to drive, with those of 60 age-
      and sex-matched epileptic patients who refrained from driving. The results showed
      that patients with epilepsy do not comply with driving restrictions, mainly for
      employment-related reasons.

PMID- 16966555
TI  - Late-onset Tay-Sachs disease: adverse effects of medications and implications for
      treatment.
AB  - The authors conducted a retrospective and brief prospective study of adverse
      effects of approximately 350 medications in 44 adults with late-onset Tay-Sachs
      disease (LOTS). Some medications were relatively safe, whereas others,
      particularly haloperidol, risperidone, and chlorpromazine, were associated with
      neurologic worsening.

PMID- 16966556
TI  - Subcortical white matter abnormalities related to drug resistance in Wilson
      disease.
AB  - Wilson disease (WD) produces typical lesions in the brain, which can aid in
      diagnosis and therapy. The authors present a drug-resistant WD case with atypical
      cerebral lesions with marked involvement of white matter as visualized on MRI
      scans. The diagnosis was confirmed by identification of mutations in the ATP7B
      gene. The case demonstrates an uncommon pathology-related cerebral copper
      accumulation and emphasizes the importance of genetic screening in the diagnosis
      of WD.

PMID- 16966557
TI  - Brain shrinkage due to acute hypernatremia.

PMID- 16966558
TI  - Occurrence of CNS demyelinating disease in patients with myasthenia gravis.
AB  - An increased incidence of multiple sclerosis (MS) has been reported in patients
      with myasthenia gravis (MG). We reviewed records of 214 patients with MG. CNS
      demyelinating disease (CNSDD) occurred in five patients (2.3%). CNSDD always
      occurred after the diagnosis of MG. Myelitis (including recurrent myelitis) was
      the most common CNS manifestation. All patients had antinuclear antibodies. CNSDD
      occurs more frequently in patients with MG and may be related to immune
      modulating treatments including thymectomy.

PMID- 16966559
TI  - Characteristics and antecedents of progressive multifocal leukoencephalopathy in
      an insured population.
AB  - Based on health insurance claims from a large U.S. health insurer, the authors
      identified 44 progressive multifocal leukoencephalopathy (PML) cases from 2002
      through 2004 and described their characteristics, including antecedent diagnoses
      and treatments as well as survival. Immunosuppressive conditions such as
      HIV/AIDS, rather than potentially immunosuppressive treatments, were the main
      antecedents of PML. A lower mortality was observed among PML patients whose
      antecedent diagnosis was HIV/AIDS, the majority of whom received highly active
      antiretroviral therapy.

PMID- 16966560
TI  - Auditory and tactile processing in a postmeningitic deaf-blind patient with a
      cochlear implant.
AB  - The authors examined the neural function of a postmeningitic deaf-blind patient
      who regained his hearing with a multichannel cochlear implant. Auditory stimuli
      activated the temporal cortices of both sides in a manner similar to that of
      controls, reflecting the successful recruitment of the auditory cortex after
      implantation. The patient's occipital lobes were deactivated during the tactile
      language task, the results of which were completely different from those before
      cochlear implantation.

PMID- 16966561
TI  - Factors predicting prognosis after decompressive hemicraniectomy for hemispheric
      infarction.
AB  - The authors reviewed 42 consecutive cases of decompressive hemicraniectomy after
      hemispheric ischemic stroke to assess predictors of outcome. On univariate
      analysis, advanced age and history of hypertension were significantly associated
      with unfavorable outcome, whereas thrombolysis was protective. Side of
      infarction, pupillary nonreactivity, degree of preoperative midline shift, and
      timing of surgery did not predict outcome. On multivariate analysis, older age
      independently predicted poor recovery (odds ratio 2.9 per 10-year increase in
      age).

PMID- 16966562
TI  - Cerebrovascular disease among patients from the Indian subcontinent.
AB  - In this study, the authors document the characteristics of South Asian (SA)
      cerebrovascular patients. A retrospective medical record review comparing SA (n =
      99) and European-American (n = 106) patients was performed. SA patients were
      younger and had a greater prevalence of diabetes, but lower prevalences of
      hyperlipidemia and tobacco use. SA patients experienced a 75% lower risk of
      cardiogenic infarctions, but a threefold increased risk of intracranial
      atherothrombosis. Risk factor modifications and secondary prevention strategies
      may differ for SA patients.

PMID- 16966563
TI  - Effects of caffeine on levodopa pharmacokinetics and pharmacodynamics in
      Parkinson disease.
AB  - The authors studied the acute effect of caffeine on the levodopa pharmacokinetics
      and pharmacodynamics in 12 patients with idiopathic Parkinson disease. This
      double-blind, randomized, crossover study revealed that caffeine shortened the
      maximal plasma concentration of levodopa, decreased the latency to levodopa
      walking and tapping motor response, and increased the magnitude of walking
      response. Caffeine administered before levodopa may improve its pharmacokinetics
      in some parkinsonian patients.

PMID- 16966564
TI  - A novel autosomal dominant restless legs syndrome locus maps to chromosome 20p13.
AB  - The authors investigated genetic factors contributing to restless legs syndrome
      (RLS) by performing a 10-cM genome-wide scan in a large French-Canadian pedigree.
      They detected an autosomal-dominant locus mapping to chromosome 20p13, with a
      maximum multipoint lod score of 3.86 at marker D20S849. This is the third
      reported autosomal-dominant locus for RLS and the first autosomal-dominant RLS
      locus in the French-Canadian population.

PMID- 16966565
TI  - Caregiver time use in ALS.
AB  - The authors evaluated the caregiver time for 70 patients with ALS. The mean
      number of caregivers per patient was 2.0 (SD 1.3). Caregiver time increased with
      worsening of disability (p = 0.0001). The most time-consuming duties were
      housekeeping, feeding, and toileting. With worsening of patients' disability,
      families relied increasingly on paid caregivers. Caregiver time is a hidden cost
      of ALS care and is a major burden for caregivers.

PMID- 16966566
TI  - Hypergraphia and the diagnosis of psychogenic attacks.

PMID- 16966567
TI  - Treatment of the gravity dependence of downbeat nystagmus with 3,4
      diaminopyridine.
AB  - The authors examined the effect of 3,4-diaminopyridine (DAP) on the gravity
      dependent (GD) vertical ocular drift component of downbeat nystagmus in 11
      patients with idiopathic cerebellar ataxia. With the head tilted downward (45
      degrees ), DAP reduced slow phase velocity (SPV) in 7 of 11 patients by 36%. Its
      efficacy correlated with the GD modulation. DAP minimizes the gravity-independent
      velocity bias and may improve deficient inhibitory cerebellar control on
      overacting otolith-ocular reflexes.

PMID- 16966568
TI  - Transient paraparesis due to right carotid stenosis with left anterior cerebral
      artery aplasia.

PMID- 16966569
TI  - Quantification of neurometabolites in subacute sclerosing panencephalitis by 1H
      MRS.
AB  - The authors studied 20 patients with subacute sclerosing panencephalitis (SSPE)
      to investigate the correlations between MRI, magnetic resonance spectroscopy
      (MRS), and clinical status. MRI findings did not correlate with clinical status.
      By contrast, all patients had reductions in N-acetyl aspartate (NAA) and increase
      in myoinositol (mI) (p < 0.01), and NAA and mI concentrations correlated with
      clinical severity (p < 0.05). During follow-up, NAA continued to decline. (1)H
      MRS may be a useful measure of disease severity and progression in SSPE.

PMID- 16966570
TI  - Anterograde amnesia with hippocampal lesions following glufosinate intoxication.

PMID- 16966571
TI  - Unilateral mydriasis from ipratropium in transplant patients.

PMID- 16966572
TI  - Distal medial plantar neuropathy in infantry soldiers.

PMID- 16966573
TI  - Eureka!

PMID- 16966574
TI  - Different degrees of right-to-left shunting predict migraine and stroke: data
      from 420 patients.

PMID- 16966575
TI  - Brain death worldwide: accepted fact but no global consensus in diagnostic
      criteria.

PMID- 16966576
TI  - Sudden deafness from stroke.

PMID- 16966577
TI  - Phosphodiesterase 5 inhibition to treat essential hypertension: is this the
      beginning of the story?

PMID- 16966578
TI  - Association between arterial properties and renal sodium handling in a general
      population.
AB  - Mean arterial pressure drives pressure-natriuresis and determines arterial
      structure and function. In a population sample, we investigated the relation
      between arterial characteristics and renal sodium handling as assessed by the
      clearance of endogenous lithium. We ultrasonographically measured diameter, cross
      sectional compliance (CC) and distensibility (DC) of the carotid, brachial, and
      femoral arteries in 1069 untreated subjects (mean age: 41.6 years; 50.1% women;
      18.8% hypertensive subjects). While accounting for covariates and standardizing
      for the sodium excretion rate in both sexes, CC and DC of the femoral artery
      increased with higher fractional distal sodium reabsorption. Differences
      associated with a 1-SD change in fractional distal reabsorption of sodium were
      51.7 mm(2)/kPax10(-3) (95% CI: 23.9 to 79.5; P=0.0002) and 0.56x10(-3)/kPa (95%
      CI: 0.17 to 0.94; P=0.004) for femoral CC and DC, respectively. In women as well
      as in men, a 1-SD increment in fractional proximal sodium reabsorption was
      associated with decreases in femoral and brachial diameter, amounting to 111.6
      mum (95% CI: 38.2 to 185.1; P=0.003) and 52.5 mum (95% CI: 10.0 to 94.9;
      P=0.016), respectively. There was no consistent association between the
      properties of the elastic carotid artery and renal sodium handling. In
      conclusion, higher fractional sodium reabsorption in the distal nephron is
      associated with higher femoral CC and DC, and higher proximal sodium reabsorption
      is associated with decreased brachial and femoral diameters. These findings
      demonstrate that there might be an influence of renal sodium handling on arterial
      properties or vice versa or that common mechanisms might influence both arterial
      and renal function.

PMID- 16966579
TI  - Too much is not enough: hypertension and sympathetic vasoconstriction in
      contracting muscles.

PMID- 16966580
TI  - Salt loading on plasma asymmetrical dimethylarginine and the protective role of
      potassium supplement in normotensive salt-sensitive asians.
AB  - Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase.
      Because endothelial NO pathway is compromised in patients with salt-sensitive
      hypertension, we investigated whether the plasma ADMA can be modulated by chronic
      salt loading in normotensive salt-sensitive persons and its relationship with NO,
      and we further determined whether or not dietary potassium supplementation can
      reverse them. Sixty normotensive subjects (aged 20 to 60 years) were selected
      from a rural community of Northern China. All of the people were sequentially
      maintained on a low-salt diet for 7 days (3 g/day, NaCl), then a high-salt diet
      for 7 days (18 g/day), and high-salt diet with potassium supplementation for
      another 7 days (4.5 g/day, KCl). After salt loading, the plasma ADMA
      concentrations increased significantly in salt-sensitive subjects (0.89+/-0.02
      micromol/L versus 0.51+/-0.02 micromol/L; P<0.05), whereas the plasma NOx levels
      reduced considerably (41.8+/-2.1 micromol/L versus 63.5+/-2.1 micromol/L;
      P<0.01). All of the abnormalities normalized when dietary potassium were
      supplemented (0.52+/-0.03 micromol/L versus 0.89+/-0.02 micromol/L for ADMA and
      58.1+/-0.9 micromol/L versus 41.8+/-2.1 micromol/L for NOx). Statistically
      significant correlations were found among plasma ADMA level, the mean blood
      pressure, and the level of NO after salt loading in normotensive salt sensitive
      individuals. Our study indicates that high dietary potassium intake reduces blood
      pressure and ADMA levels while increasing NO bioactivity in normotensive salt
      sensitive but not salt-resistant Asian subjects after salt loading.

PMID- 16966581
TI  - Central action of increased osmolality to support blood pressure in
      deoxycorticosterone acetate-salt rats.
AB  - To test the hypothesis that increased osmolality contributes to hypertension in
      deoxycorticosterone acetate (DOCA)-salt-hypertensive rats by acting in the brain,
      DOCA-salt and Sham-salt rats were instrumented with bilateral, nonoccluding
      intracarotid and femoral catheters. Two weeks prior, rats were uninephrectomized
      and received subcutaneous implants with or without DOCA (65 mg) and began
      drinking salt water (1% NaCl and 0.2% KCl). DOCA-salt rats (n=28) exhibited
      elevated blood pressure (159+/-4 mm Hg; P<0.05) and heart rate (392+/-10 bpm;
      P<0.05) compared with Sham-salt animals (n=5; blood pressure: 107+/-5 mm Hg;
      heart rate: 355+/-10 bpm). Bilateral intracarotid infusion of hypotonic fluid
      (osmolality: approximately 40 mOsm/L), which lowers osmolality of blood to the
      brain by approximately 2%, rapidly decreased blood pressure in DOCA-salt rats (
      22+/-4 mm Hg after 15 minutes; P<0.05; n=7) but not Sham-salt rats (2+/-2 mm Hg;
      n=5). Hypotonic fluid infused intravenously did not lower blood pressure (0+/-2
      mm Hg) in DOCA-salt rats (n=7). In DOCA-salt rats pretreated with a V(1)
      vasopressin antagonist (Manning compound, 5 microg, IV), intracarotid hypotonic
      infusion still decreased blood pressure (-10+/-3 mm Hg; P<0.05; n=9), but the
      response was smaller (P<0.05). Finally, in DOCA-salt rats (n=4) pretreated with
      the V(1) antagonist and the ganglionic blocker hexamethonium, decreasing
      osmolality of blood to the brain did not reduce blood pressure. These data
      indicate that, in DOCA-salt rats, hypertonicity acts in the brain to support
      blood pressure, in part by stimulating vasopressin secretion and in part by
      stimulating another rapidly reversible mechanism, likely the sympathetic nervous
      system.

PMID- 16966582
TI  - Functional expression of the TRPM4 cationic current in ventricular cardiomyocytes
      from spontaneously hypertensive rats.
AB  - Cardiac hypertrophy is associated with electrophysiological modifications,
      including modification of action potential shape that can give rise to
      arrhythmias. We report here a higher detection of a calcium-activated
      nonselective cation current in cardiomyocytes of spontaneously hypertensive rats
      (SHRs), a model of hypertension and heart hypertrophy when compared with Wistar
      Kyoto (WKY) rat, its normotensive equivalent. Freshly isolated cells from the
      left ventricles of 3- to 6-month-old WKY rats or SHRs were used for patch-clamp
      recordings. In inside-out patches, the channel presented a linear conductance of
      25+/-0.5 pS, did not discriminate Na(+) over K(+), and was not permeable to
      Ca(2+). Open probability was increased by depolarization and a rise in
      [Ca(2+)](i) (dissociation constant=10+/-5.4 micromol/L) but reduced by 0.5 mmol/L
      [ATP](i), 10 micromol/L glibenclamide, or flufenamic acid (IC(50)=5.5+/-1.7
      micromol/L). Thus, it owns the fingerprint of the TRPM4 current. Although rarely
      detected in WKY cardiomyocytes, the current was present in >50% of patches from
      SHR cardiomyocytes. Moreover, by performing RT-PCR from ventricular samples, we
      observed that TRPM4 mRNA detection was higher in SHRs than in WKY rats. We
      propose that a TRPM4 current is expressed in ventricular cardiomyocytes from
      SHRs. According to its properties, this channel may contribute to the transient
      inward current implicated in delayed-after-depolarizations observed during
      [Ca(2+)] overload of cardiomyocytes.

PMID- 16966583
TI  - Nitrative inactivation of thioredoxin-1 and its role in postischemic myocardial
      apoptosis.
AB  - BACKGROUND: Intracellular proteins involved in oxidative stress and apoptosis are
      nitrated in diseased tissues but not in normal tissues; definitive evidence to
      support a causative link between a specific protein that is nitratively modified
      with tissue injury in a specific disease is limited, however. The aims of the
      present study were to determine whether thioredoxin (Trx), a novel antioxidant
      and antiapoptotic molecule, is susceptible to nitrative inactivation and to
      establish a causative link between Trx nitration and postischemic myocardial
      apoptosis. METHODS AND RESULTS: In vitro exposure of human Trx-1 to 3
      morpholinosydnonimine resulted in significant Trx-1 nitration and almost
      abolished Trx-1 activity. 3-morpholinosydnonimine-induced nitrative Trx-1
      inactivation was completely blocked by MnTE-2-PyP(5+) (a superoxide dismutase
      mimetic) and markedly attenuated by PTIO (a nitric oxide scavenger).
      Administration of either reduced or oxidized Trx-1 in vivo attenuated myocardial
      ischemia/reperfusion injury (>50% reduction in apoptosis and infarct size,
      P<0.01). However, administration of nitrated Trx-1 failed to exert a
      cardioprotective effect. In cardiac tissues obtained from ischemic/reperfused
      heart, significant Trx-1 nitration was detected, Trx activity was markedly
      inhibited, Trx-1/ASK1 (apoptosis signal-regulating kinase-1) complex formation
      was abolished, and apoptosis signal-regulating kinase-1 activity was increased.
      Treatment with either FP15 (a peroxynitrite decomposition catalyst) or MnTE-2
      PyP(5+) 10 minutes before reperfusion blocked nitrative Trx inactivation,
      attenuated apoptosis signal-regulating kinase-1 activation, and reduced
      postischemic myocardial apoptosis. CONCLUSIONS: These results strongly suggest
      that nitrative inactivation of Trx plays a proapoptotic role under those
      pathological conditions in which production of reactive nitrogen species is
      increased and that antinitrating treatment may have therapeutic value in those
      diseases, such as myocardial ischemia/reperfusion, in which pathological
      apoptosis is increased.

PMID- 16966584
TI  - Analytical identification of ideal pulmonary-systemic flow balance in patients
      with bidirectional cavopulmonary shunt and univentricular circulation: oxygen
      delivery or tissue oxygenation?
AB  - BACKGROUND: In the present study, we extended previous mathematical modeling work
      on patients with bidirectional cavopulmonary ("bidirectional Glenn") anastomosis
      to assess the potential utility of several descriptors of oxygen status. We set
      out to determine which of these descriptors best represents the overall tissue
      oxygenation. We also introduce a new descriptor, SO2min, defined as the lower of
      the superior and inferior vena cava oxygen saturations. METHODS AND RESULTS: The
      application of differential calculus to a model of oxygen physiology of patients
      with bidirectional Glenn allowed simultaneous assessment of all possible
      distributions of blood flow and metabolic rate between upper and lower body,
      across all cardiac outputs, total metabolic rates, and oxygen-carrying
      capacities. When total cardiac output is fixed, although it may intuitively seem
      best to distribute flow to maximize oxygen delivery (total, upper body, or lower
      body), we found that for each variable, there are situations in which its
      maximization seriously deprives flow to the upper or lower circulation. In
      contrast, maximizing SO2min always gives physiologically sensible results. If the
      majority of metabolism is in the upper body (typical of infancy), then
      oxygenation is optimized when flow distribution matches metabolic distribution.
      In contrast, if the majority of metabolism is in the lower body (typical of older
      children and during exercise), oxygenation is optimal when flows are equal.
      CONCLUSIONS: In patients with bidirectional cavopulmonary anastomosis, because
      there is a tradeoff between flow distribution and saturation, it is unwise to
      concentrate on maximizing oxygen delivery. Maximizing systemic venous saturations
      (especially SO2min) is conceptually different and physiologically preferable for
      tissue oxygenation.

PMID- 16966585
TI  - Localization of Na+ channel isoforms at the atrioventricular junction and
      atrioventricular node in the rat.
AB  - BACKGROUND: The electrical activity of the atrioventricular node (AVN) is
      functionally heterogeneous, but how this relates to distinct cell types and the 3
      dimensional structure of the AVN is unknown. To address this, we have studied the
      expression of Na(V)1.5 and other Na+ channel isoforms in the AVN. METHODS AND
      RESULTS: The rat AVN was identified by Masson's trichrome staining together with
      immunolabeling of marker proteins: connexin40, connexin43, desmoplakin, atrial
      natriuretic peptide, and hyperpolarization-activated and cyclic nucleotide-gated
      channel 4. Na+ channel expression was investigated with immunohistochemistry with
      isoform-specific Na+ channel antibodies. Na(V)1.1 was distributed in a similar
      manner to Na(V)1.5. Na(V)1.2 was not detected. Na(V)1.3 labeling was present in
      nerve fibers and cell bodies (but not myocytes) and was abundant in the
      penetrating atrioventricular (AV) bundle and the common bundle but was much less
      abundant in other regions. Na(V)1.5 labeling was abundant in the atrial and
      ventricular myocardium and the left bundle branch. Na(V)1.5 labeling was absent
      in the open node, penetrating AV bundle, AV ring bundle, and common bundle but
      present at a reduced level in the inferior nodal extension and transitional zone.
      Na(V)1.6 was not detected. CONCLUSIONS: Our findings provide molecular evidence
      of multiple electrophysiological cell types at the AV junction. Impaired AV
      conduction as a result of mutations in or loss of Na(V)1.5 must be the result of
      impaired conduction in the AVN inputs (inferior nodal extension and transitional
      zone) or output (bundle branches) rather than the AVN itself (open node and
      penetrating AV bundle).

PMID- 16966586
TI  - Clinical utility and safety of a protocol for noncardiac and cardiac magnetic
      resonance imaging of patients with permanent pacemakers and implantable
      cardioverter defibrillators at 1.5 tesla.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is an important diagnostic modality
      currently unavailable for millions of patients because of the presence of
      implantable cardiac devices. We sought to evaluate the diagnostic utility and
      safety of noncardiac and cardiac MRI at 1.5T using a protocol that incorporates
      device selection and programming and limits the estimated specific absorption
      rate of MRI sequences. METHODS AND RESULTS: Patients with no imaging alternative
      and with devices shown to be MRI safe by in vitro phantom and in vivo animal
      testing were enrolled. Of 55 patients who underwent 68 MRI studies, 31 had a
      pacemaker, and 24 had an implantable defibrillator. Pacing mode was changed to
      "asynchronous" for pacemaker-dependent patients and to "demand" for others.
      Magnet response and tachyarrhythmia functions were disabled. Blood pressure, ECG,
      oximetry, and symptoms were monitored. Efforts were made to limit the system
      estimated whole-body average specific absorption rate to 2.0 W/kg (successful in
      >99% of sequences) while maintaining the diagnostic capability of MRI. No
      episodes of inappropriate inhibition or activation of pacing were observed. There
      were no significant differences between baseline and immediate or long-term
      (median 99 days after MRI) sensing amplitudes, lead impedances, or pacing
      thresholds. Diagnostic questions were answered in 100% of nonthoracic and 93% of
      thoracic studies. Clinical findings included diagnosis of vascular abnormalities
      (9 patients), diagnosis or staging of malignancy (9 patients), and assessment of
      cardiac viability (13 patients). CONCLUSIONS: Given appropriate precautions,
      noncardiac and cardiac MRI can potentially be safely performed in patients with
      selected implantable pacemaker and defibrillator systems.

PMID- 16966587
TI  - Strategy for safe performance of extrathoracic magnetic resonance imaging at 1.5
      tesla in the presence of cardiac pacemakers in non-pacemaker-dependent patients:
      a prospective study with 115 examinations.
AB  - BACKGROUND: The purpose of the present study was to evaluate a strategy for safe
      performance of extrathoracic magnetic resonance imaging (MRI) in non-pacemaker
      dependent patients with cardiac pacemakers. METHODS AND RESULTS: Inclusion
      criteria were presence of a cardiac pacemaker and urgent clinical need for an MRI
      examination. Pacemaker-dependent patients and those requiring examinations of the
      thoracic region were excluded. The study group consisted of 82 pacemaker patients
      who underwent a total of 115 MRI examinations at 1.5T. To minimize radiofrequency
      related lead heating, the specific absorption rate was limited to 1.5 W/kg. All
      pacemakers were reprogrammed before MRI: If heart rate was <60 bpm, the
      asynchronous mode was programmed to avoid magnetic resonance (MR)-induced
      inhibition; if heart rate was >60 bpm, sense-only mode was used to avoid MR
      induced competitive pacing and potential proarrhythmia. Patients were monitored
      with ECG and pulse oximetry. All pacemakers were interrogated immediately before
      and after the MRI examination and after 3 months, including measurement of pacing
      capture threshold (PCT) and serum troponin I levels. All MR examinations were
      completed safely. Inhibition of pacemaker output or induction of arrhythmias was
      not observed. PCT increased significantly from pre- to post-MRI (P=0.017). In 2
      of 195 leads, an increase in PCT was only detected at follow-up. In 4 of 114
      examinations, troponin increased from a normal baseline value to above normal
      after MRI, and in 1 case (troponin pre-MRI 0.02 ng/mL, post-MRI 0.16 ng/mL), this
      increase was associated with a significant increase in PCT. CONCLUSIONS:
      Extrathoracic MRI of non-pacemaker-dependent patients can be performed with an
      acceptable risk-benefit ratio under controlled conditions and by taking both MR-
      and pacemaker-related precautions.

PMID- 16966588
TI  - Cost-effectiveness of coronary artery bypass grafts versus percutaneous coronary
      intervention for revascularization of high-risk patients.
AB  - BACKGROUND: A Department of Veterans Affairs Cooperative Study randomized high
      risk patients with medically refractory myocardial ischemia, a group largely
      excluded from previous trials, to urgent revascularization with either
      percutaneous coronary intervention (PCI) or coronary artery bypass grafting
      (CABG). The present study examined the cost-effectiveness of PCI versus CABG for
      these high-risk patients. METHODS AND RESULTS: Of 454 patients at 16 Department
      of Veterans Affairs medical centers, 445 were available for the economic analysis
      (218 PCI and 227 CABG patients). Total costs were assessed at 3 and 5 years from
      the third-party payer's perspective, and effectiveness was measured by survival.
      After 3 years, average total costs were 63,896 dollars for PCI versus 84,364
      dollars for CABG patients, a difference of 20,468 dollars (95% confidence
      interval [CI] 13,918 dollars to 27,569 dollars). CIs were estimated by
      bootstrapping. Survival at 3 years was 0.82 for PCI versus 0.79 for CABG patients
      (P=0.34). Precision of the cost-effectiveness estimates were assessed by
      bootstrapping. PCI was less costly and more effective at 3 years in 92.6% of the
      bootstrap replications. After 5 years, average total costs were 81,790 dollars
      for PCI versus 100,522 dollars for CABG patients, a difference of 18,732 dollars
      (95% CI 9873 dollars to 27,831 dollars), whereas survival at 5 years was 0.75 for
      PCI patients versus 0.70 for CABG patients (P=0.21). At 5 years, PCI remained
      less costly and more effective in 89.4% of the bootstrap replications.
      CONCLUSIONS: PCI was less costly and at least as effective for the urgent
      revascularization of medically refractory, high-risk patients over 5 years.

PMID- 16966589
TI  - An unusual explanation for episodic dyspnea.

PMID- 16966590
TI  - Rheumatic myocarditis masquerading as left ventricle tumor.

PMID- 16966591
TI  - Unmasking of the Brugada syndrome phenotype during the acute phase of amiodarone
      infusion.

PMID- 16966592
TI  - Letter by Kurth regarding article, "Nonsteroidal antiinflammatory drugs,
      acetaminophen, and the risk of cardiovascular events".

PMID- 16966593
TI  - Pioneers in cardiology: Maarten Simoons, MD. Interview by Robert Short.

PMID- 16966594
TI  - Sudden cardiac death: better understanding of risks, mechanisms, and treatment.

PMID- 16966595
TI  - Inflamed joints and stiff arteries: is rheumatoid arthritis a cardiovascular risk
      factor?

PMID- 16966596
TI  - Navigating the crossroads of coronary artery disease and heart failure.

PMID- 16966597
TI  - Sleep disruption, oxidative stress, and aging: new insights from fruit flies.

PMID- 16966598
TI  - A mutation in the translation initiation codon of Gata-1 disrupts megakaryocyte
      maturation and causes thrombocytopenia.
AB  - We have generated mice from a N-ethyl-N-nitrosourea mutagenesis screen that carry
      a mutation in the translation initiation codon of Gata-1, termed Plt13, which is
      equivalent to mutations found in patients with acute megakaryoblastic leukemia
      and Down syndrome. The Gata-1 locus is present on the X chromosome in humans and
      in mice. Male mice hemizygous for the mutation (Gata-1Plt13/Y) failed to produce
      red blood cells and died during embryogenesis at a similar stage to Gata-1-null
      animals. Female mice that carry the Plt13 mutation are mosaic because of random
      inactivation of the X chromosome. Adult Gata-1Plt13/+ females were not anemic,
      but they were thrombocytopenic and accumulated abnormal megakaryocytes without a
      concomitant increase in megakaryocyte progenitor cells. Gata-1Plt13/+ mice
      contained large numbers of blast-like colony-forming cells, particularly in the
      fetal liver, but also in adult spleen and bone marrow, from which continuous mast
      cells lines were readily derived. Although the equivalent mutation to Gata-1Plt13
      in humans results in production of GATA-1s, a short protein isoform initiated
      from a start codon downstream of the mutated initiation codon, Gata-1s was not
      detected in Gata-1Plt13/+ mice.

PMID- 16966599
TI  - Ca2+/calmodulin-dependent protein kinase II (CaMKII) is activated by calmodulin
      with two bound calciums.
AB  - Changes in synaptic strength that underlie memory formation in the CNS are
      initiated by pulses of Ca2+ flowing through NMDA-type glutamate receptors into
      postsynaptic spines. Differences in the duration and size of the pulses determine
      whether a synapse is potentiated or depressed after repetitive synaptic activity.
      Calmodulin (CaM) is a major Ca2+ effector protein that binds up to four Ca2+
      ions. CaM with bound Ca2+ can activate at least six signaling enzymes in the
      spine. In fluctuating cytosolic Ca2+, a large fraction of free CaM is bound to
      fewer than four Ca2+ ions. Binding to targets increases the affinity of CaM's
      remaining Ca2+-binding sites. Thus, initial binding of CaM to a target may depend
      on the target's affinity for CaM with only one or two bound Ca2+ ions. To study
      CaM-dependent signaling in the spine, we designed mutant CaMs that bind Ca2+ only
      at the two N-terminal or two C-terminal sites by using computationally designed
      mutations to stabilize the inactivated Ca2+-binding domains in the "closed" Ca2+
      free conformation. We have measured their interactions with CaMKII, a major
      Ca2+/CaM target that mediates initiation of long-term potentiation. We show that
      CaM with two Ca2+ ions bound in its C-terminal lobe not only binds to CaMKII with
      low micromolar affinity but also partially activates kinase activity. Our results
      support the idea that competition for binding of CaM with two bound Ca2+ ions may
      influence significantly the outcome of local Ca2+ signaling in spines and,
      perhaps, in other signaling pathways.

PMID- 16966600
TI  - Extreme genetic risk for type 1A diabetes.
AB  - Type 1A diabetes (T1D) is an autoimmune disorder the risk of which is increased
      by specific HLA DR/DQ alleles [e.g., DRB1*03-DQB1*0201 (DR3) or DRB1*04-DQB1*0302
      (DR4)]. The genotype associated with the highest risk for T1D is the DR3/4-DQ8
      (DQ8 is DQA1*0301, DQB1*0302) heterozygous genotype. We determined HLA-DR and -DQ
      genotypes at birth and analyzed DR3/4-DQ8 siblings of patients with T1D for
      identical-by-descent HLA haplotype sharing (the number of haplotypes inherited in
      common between siblings). The children were clinically followed with prospective
      measurement of anti-islet autoimmunity and for progression to T1D. Risk for islet
      autoimmunity dramatically increased in DR3/4-DQ8 siblings who shared both HLA
      haplotypes with their diabetic proband sibling (63% by age 7, and 85% by age 15)
      compared with siblings who did not share both HLA haplotypes with their diabetic
      proband sibling (20% by age 15, P < 0.01). 55% sharing both HLA haplotypes
      developed diabetes by age 12 versus 5% sharing zero or one haplotype (P = 0.03).
      Despite sharing both HLA haplotypes with their proband, siblings without the HLA
      DR3/4-DQ8 genotype had only a 25% risk for T1D by age 12. The risk for T1D in the
      DR3/4-DQ8 siblings sharing both HLA haplotypes with their proband is remarkable
      for a complex genetic disorder and provides evidence that T1D is inherited with
      HLA-DR/DQ alleles and additional MHC-linked genes both determining major risk. A
      subset of siblings at extremely high risk for T1D can now be identified at birth
      for trials to prevent islet autoimmunity.

PMID- 16966601
TI  - Molecular switch for alternative conformations of the HIV-1 V3 region:
      implications for phenotype conversion.
AB  - HIV-1 coreceptor usage plays a critical role in virus tropism and pathogenesis. A
      switch from CCR5- to CXCR4-using viruses occurs during the course of HIV-1
      infection and correlates with subsequent disease progression. A single mutation
      at position 322 within the V3 loop of the HIV-1 envelope glycoprotein gp120, from
      a negatively to a positively charged residue, was found to be sufficient to
      switch an R5 virus to an X4 virus. In this study, the NMR structure of the V3
      region of an R5 strain, HIV-1(JR-FL), in complex with an HIV-1-neutralizing
      antibody was determined. Positively charged and negatively charged residues at
      positions 304 and 322, respectively, oppose each other in the beta-hairpin
      structure, enabling a favorable electrostatic interaction that stabilizes the
      postulated R5 conformation. Comparison of the R5 conformation with the postulated
      X4 conformation of the V3 region (positively charged residue at position 322)
      reveals that electrostatic repulsion between residues 304 and 322 in X4 strains
      triggers the observed one register shift in the N-terminal strand of the V3
      region. We posit that electrostatic interactions at the base of the V3 beta
      hairpin can modulate the conformation and thereby influence the phenotype switch.
      In addition, we suggest that interstrand cation-pi interactions between
      positively charged and aromatic residues induce the switch to the X4 conformation
      as a result of the S306R mutation. The existence of three pairs of identical (or
      very similar) amino acids in the V3 C-terminal strand facilitates the switch
      between the R5 and X4 conformations.

PMID- 16966602
TI  - Efficiency of carcinogenesis with and without a mutator mutation.
AB  - Carcinogenesis involves the acquisition of multiple genetic changes altering
      various cellular phenotypes. These changes occur within the fixed time period of
      a human lifespan, and mechanisms that accelerate this process are more likely to
      result in clinical cancers. Mutator mutations decrease genome stability and,
      hence, accelerate the accumulation of random mutations, including those in
      oncogenes and tumor suppressor genes. However, if the mutator mutation is not in
      itself oncogenic, acquiring that mutation would add an extra, potentially time
      consuming step in carcinogenesis. We present a deterministic mathematical model
      that allows quantitative prediction of the efficiency of carcinogenesis with and
      without a mutator mutation occurring at any time point in the process. By
      focusing on the ratio of probabilities of pathways with and without mutator
      mutations within cell lineages, we can define the frequency or importance of
      mutator mutations in populations independently of absolute rates and circumvent
      the question of whether mutator mutations are "necessary" for cancers to evolve
      within a human lifetime. We analyze key parameters that predict the relative
      contribution of mutator mutants in carcinogenesis. Mechanisms of carcinogenesis
      involving mutator mutations are more likely if they occur early. Involvement of
      mutator mutations in carcinogenesis is favored by an increased initial mutation
      rate, by greater fold-increase in mutation rate due to the mutator mutation, by
      increased required steps in carcinogenesis, and by increased number of cell
      generations to the development of cancer.

PMID- 16966603
TI  - Transcriptional activation by EBV nuclear antigen 1 is essential for the
      expression of EBV's transforming genes.
AB  - EBV is a paradigm for human tumor viruses because, although it infects most
      people benignly, it also can cause a variety of cancers. Both in vivo and in
      vitro, EBV infects B lymphocytes in G0, induces them to become blasts, and can
      maintain their proliferation in cell culture or in vivo as tumors. How EBV
      succeeds in these contrasting cellular environments in expressing its genes that
      control the host has not been explained. We have genetically dissected the EBV
      nuclear antigen 1 (EBNA1) gene that is required for replication of the viral
      genome, to elucidate its possible role in the transcription of viral genes.
      Strikingly, EBNA1 is essential to drive transcription of EBV's transforming genes
      after infection of primary B lymphocytes.

PMID- 16966604
TI  - The cephalic neural crest exerts a critical effect on forebrain and midbrain
      development.
AB  - Encephalisation is the most important characteristic in the evolutionary
      transition leading from protochordates to vertebrates. This event has coincided
      with the emergence of a transient and pluripotent structure, the neural crest
      (NC), which is absent in protochordates. In vertebrates, NC provides the rostral
      cephalic vesicles with skeletal protection and functional vascularization. The
      surgical extirpation of the cephalic NC, which is responsible for building up the
      craniofacial skeleton, results in the absence of facial skeleton together with
      severe defects of preotic brain development, leading to exencephaly. Here, we
      have analyzed the role of the NC in forebrain and midbrain development. We show
      that (i) NC cells (NCC) control Fgf8 expression in the anterior neural ridge,
      which is considered the prosencephalic organizer; (ii) the cephalic NCC are
      necessary for the closure of the neural tube; and (iii) NCC contribute to the
      proper patterning of genes that are expressed in the prosencephalic and
      mesencephalic alar plate. Along with the development of the roof plate, NCC also
      concur to the patterning of the pallial and subpallial structures. We show that
      the NC-dependent production of FGF8 in anterior neural ridge is able to restrict
      Shh expression to the ventral prosencephalon. All together, these findings
      support the notion that the cephalic NC controls the formation of craniofacial
      structures and the development of preotic brain.

PMID- 16966605
TI  - Identification of Clostridium difficile toxin B cardiotoxicity using a zebrafish
      embryo model of intoxication.
AB  - Clostridium difficile toxin B (TcdB) has been studied extensively by using cell
      free systems and tissue culture, but, like many bacterial toxins, the in vivo
      targets of TcdB are unknown and have been difficult to elucidate with traditional
      animal models. In the current study, the transparent Danio rerio (zebrafish)
      embryo was used as a model for imaging of in vivo TcdB localization and organ
      specific damage in real time. At 24 h after treatment, TcdB was found to localize
      at the pericardial region, and zebrafish exhibited the first signs of
      cardiovascular damage, including a 90% reduction in systemic blood flow and a 20%
      reduction in heart rate. Within 72 h of exposure to TcdB, the ventricle chamber
      of the heart became deformed and was unable to contract or pump blood, and the
      fish exhibited extensive pericardial edema. In line with the observed defects in
      ventricle contraction, TcdB was found to directly disrupt coordinated
      contractility and rhythmicity in primary cardiomyocytes. Furthermore, using a
      caspase-3 inhibitor, we were able to block TcdB-related cardiovascular damage and
      prevent zebrafish death. These findings present an insight into the in vivo
      targets of TcdB, as well as demonstrate the strength of the zebrafish embryo as a
      tractable model for identification of in vivo targets of bacterial toxins and
      evaluation of novel candidate therapeutics.

PMID- 16966606
TI  - Ancestral reconstruction of the ligand-binding pocket of Family C G protein
      coupled receptors.
AB  - The metabotropic glutamate receptors (mGluRs) within the Family C subclass of G
      protein-coupled receptors are crucial modulators of synaptic transmission.
      However, their closest relatives include a diverse group of sensory receptors
      whose biological functions are not associated with neurotransmission, raising the
      question of the evolutionary origin of amino acid-binding Family C receptors. A
      common feature of most, if not all, functional Family C receptors is the presence
      of an amino acid-binding site localized within the large extracellular Venus
      flytrap domain. Here, we used maximum likelihood methods to infer the ancestral
      state of key residues in the amino acid-binding pocket of a primordial Family C
      receptor. These residues were reconstructed in the background of the fish 5.24
      chemosensory receptor, a broad-spectrum amino acid-activated receptor. Unlike the
      WT 5.24 receptor, which was not activated by mGluR agonists and displayed low
      sensitivity toward l-glutamate, the reconstructed ancestral receptor possessed a
      pharmacological profile characterized by high affinity for both l-glutamate and
      selective Group I mGluR agonists. This pharmacological phenotype could be largely
      recapitulated by mutating only two residues in the 5.24 receptor-binding pocket.
      Our results suggest that this primordial Family C receptor may have arisen early
      in metazoan evolution and that it already was preadapted as a glutamate receptor
      for its later use at excitatory synapses in glutamate-mediated neurotransmission.

PMID- 16966607
TI  - Crocidolite asbestos and SV40 are cocarcinogens in human mesothelial cells and in
      causing mesothelioma in hamsters.
AB  - Only a fraction of subjects exposed to asbestos develop malignant mesothelioma
      (MM), suggesting that additional factors may render some individuals more
      susceptible. We tested the hypothesis that asbestos and Simian virus (SV40) are
      cocarcinogens. Asbestos and SV40 in combination had a costimulatory effect in
      inducing ERK1/2 phosphorylation and activator protein-1 (AP-1) activity in both
      primary Syrian hamster mesothelial cells (SHM) and primary human mesothelial
      cells (HM). Ap-1 activity caused the expression and activation of matrix
      metalloprotease (MMP)-1 and MMP-9, which in turn led to cell invasion.
      Experiments using siRNA and chemical inhibitors confirmed the specificity of
      these results. The same effects were observed in HM and SHM. Experiments in
      hamsters showed strong cocarcinogenesis between asbestos and SV40: SV40 did not
      cause MM, asbestos caused MM in 20% of hamsters, and asbestos and SV40 together
      caused MM in 90% of hamsters. Significantly lower amounts of asbestos were
      sufficient to cause MM in animals infected with SV40. Our results indicate that
      mineral fibers and viruses can be cocarcinogens and suggest that lower amounts of
      asbestos may be sufficient to cause MM in individuals infected with SV40.

PMID- 16966608
TI  - Phoretic nest parasites use sexual deception to obtain transport to their host's
      nest.
AB  - Cooperative behaviors are common among social insects such as bees, wasps, ants,
      and termites, but they have not been reported from insect species that use
      aggressive mimicry to manipulate and exploit prey or hosts. Here we show that
      larval aggregations of the blister beetle Meloe franciscanus, which parasitize
      nests of the solitary bee Habropoda pallida, cooperate to exploit the sexual
      communication system of their hosts by producing a chemical cue that mimics the
      sex pheromone of the female bee. Male bees are lured to larval aggregations, and
      upon contact (pseudocopulation) the beetle larvae attach to the male bees. The
      larvae transfer to female bees during mating and subsequently are transported to
      the nests of their hosts. To mimic the chemical and visual signals of female bees
      effectively, the parasite larvae must cooperate, emphasizing the adaptive value
      of cooperation between larvae. The aggressive chemical mimicry by the beetle
      larvae and their subsequent transport to their hosts' nests by the hosts
      themselves provide an efficient solution to the problem of locating a critical
      but scarce resource in a harsh environment.

PMID- 16966609
TI  - Cross-protective immunity can account for the alternating epidemic pattern of
      dengue virus serotypes circulating in Bangkok.
AB  - Dengue virus, the causative agent of dengue fever and its more serious
      manifestation dengue hemorrhagic fever, is widespread throughout tropical and
      subtropical regions. The virus exists as four distinct serotypes, all of which
      have cocirculated in Bangkok for several decades with epidemic outbreaks
      occurring every 8-10 years. We analyze time-series data of monthly infection
      incidence, revealing a distinctive pattern with epidemics of serotypes 1, 2, and
      3 occurring at approximately the same time and an isolated epidemic of serotype 4
      occurring in the intervening years. Phylogenetic analysis of virus samples
      collected over the same period shows that clade replacement events are linked to
      the epidemic cycle and indicates that there is an interserotypic immune reaction.
      Using an epidemic model with stochastic seasonal forcing showing 8- to 10-year
      epidemic oscillations, we demonstrate that moderate cross-protective immunity
      gives rise to persistent out-of-phase oscillations similar to those observed in
      the data, but that strong or weak cross-protection or cross-enhancement only
      produces in-phase patterns. This behavior suggests that the epidemic pattern
      observed in Bangkok is the result of cross-protective immunity and may be
      significantly altered by changes in the interserotypic immune reaction.

PMID- 16966610
TI  - Rapid nongenomic actions of thyroid hormone.
AB  - The binding of thyroid hormone to the thyroid hormone receptor (TR) mediates
      important physiological effects. However, the transcriptional effects of TR
      mediated by the thyroid response element (TRE) cannot explain many actions of
      thyroid hormone. We postulate that TR can initiate rapid, non-TRE-mediated
      effects in the cardiovascular system through cross-coupling to the
      phosphatidylinositol 3-kinase (PI3-kinase)/protein kinase Akt pathway. In
      vascular endothelial cells, the predominant TR isoform is TRalpha1. Treatment of
      endothelial cells with L-3,5,3'-triiodothyronine (T3) increased the association
      of TRalpha1 with the p85alpha subunit of PI3-kinase, leading to the
      phosphorylation and activation of Akt and endothelial nitric oxide synthase
      (eNOS). The activation of Akt and eNOS by T3 was abolished by the PI3-kinase
      inhibitors, LY294002 and wortmannin, but not by the transcriptional inhibitor,
      actinomycin D. To determine the physiological relevance of this PI3-kinase/Akt
      pathway, we administered T3 to mice undergoing transient focal cerebral ischemia.
      Compared with vehicle, a single bolus infusion of T3 rapidly increased Akt
      activity in the brain, decreased mean blood pressure, reduced cerebral infarct
      volume, and improved neurological deficit score. These neuroprotective effects of
      T3 were greatly attenuated or absent in eNOS-/- and TRalpha1-/-beta-/- mice and
      were completely abolished in WT mice pretreated with LY294002 or a T3 antagonist,
      NH-3. These findings indicate that the activation of PI3-kinase/Akt pathways can
      mediate some of the rapid, non-TRE effects of TR and suggest that the activation
      of Akt and eNOS contributes to some of the acute vasodilatory and neuroprotective
      effects of thyroid hormone.

PMID- 16966611
TI  - Progesterone blocks estrogen-induced DNA synthesis through the inhibition of
      replication licensing.
AB  - In the uterus, progesterone (P4) acts early in G1 as a physiological inhibitor of
      estradiol-17beta (E2)-induced epithelial cell proliferation. Gene expression
      profiling of uterine epithelial cell RNA isolated 3 h after hormonal treatment of
      ovariectomized mice revealed the co-coordinate down-regulation by P4 of >20 genes
      whose functions are associated with DNA replication. This group included all of
      the minichromosome maintenance (MCM) proteins that are required for DNA
      replication licensing. E2 regulated loading of these MCM proteins onto chromatin
      in parallel with its induction of DNA synthesis. E2 caused this chromatin loading
      by retention of MCM proteins in the nucleus and through the induction of the
      loading factor Cdt1, which is necessary for the MCM heterohexamer to bind to the
      origin of DNA replication. P4 dramatically reduced the binding of the MCMs to
      chromatin by a number of mechanisms. First, MCM mRNA and protein abundance was
      down-regulated. Second, P4 inhibited the E2 induction of Cdt1. Third, P4
      treatment sequestered the normally nuclear MCM proteins into the cytoplasm. This
      reduced MCM binding resulted in the complete inhibition of E2-induced DNA
      synthesis by P4. These data reveal mechanisms not only for female sex steroid
      hormone action but also in the regulation of DNA replication licensing.

PMID- 16966612
TI  - Mg2+-RNA interaction free energies and their relationship to the folding of RNA
      tertiary structures.
AB  - Mg2+ ions are very effective at stabilizing tertiary structures in RNAs. In most
      cases, folding of an RNA is so strongly coupled to its interactions with Mg2+
      that it is difficult to separate free energies of Mg2+-RNA interactions from the
      intrinsic free energy of RNA folding. To devise quantitative models accounting
      for this phenomenon of Mg2+-induced RNA folding, it is necessary to independently
      determine Mg2+-RNA interaction free energies for folded and unfolded RNA forms.
      In this work, the energetics of Mg2+-RNA interactions are derived from an assay
      that measures the effective concentration of Mg2+ in the presence of RNA. These
      measurements are used with other measures of RNA stability to develop an overall
      picture of the energetics of Mg2+-induced RNA folding. Two different RNAs are
      discussed, a pseudoknot and an rRNA fragment. Both RNAs interact strongly with
      Mg2+ when partially unfolded, but the two folded RNAs differ dramatically in
      their inherent stability in the absence of Mg2+ and in the free energy of their
      interactions with Mg2+. From these results, it appears that any comprehensive
      framework for understanding Mg2+-induced stabilization of RNA will have to (i)
      take into account the interactions of ions with the partially unfolded RNAs and
      (ii) identify factors responsible for the widely different strengths with which
      folded tertiary structures interact with Mg2+.

PMID- 16966614
TI  - The quantum MacMahon Master Theorem.
AB  - We state and prove a quantum generalization of MacMahon's celebrated Master
      Theorem and relate it to a quantum generalization of the boson-fermion
      correspondence of physics.

PMID- 16966613
TI  - Testing the importance of p27 degradation by the SCFskp2 pathway in murine models
      of lung and colon cancer.
AB  - Decreased expression of the CDK inhibitor p27kip1 in human tumors directly
      correlates with increased resistance to chemotherapies, increased rates of
      metastasis, and an overall increased rate of patient mortality. It is thought
      that decreased p27 expression in tumors is caused by increased proteasomal
      turnover, in particular activation of the pathway governed by the SCFskp2 E3
      ubiquitin protein ligase. We have directly tested the importance of the SCFskp
      mediated degradation of p27 in tumorigenesis by analyzing the tumor
      susceptibility of mice that express a form of p27 that cannot be ubiquitinated
      and degraded by this pathway (p27T187A). In mouse models of both lung and colon
      cancer down-regulation of p27 promotes tumorigenesis. However, we found that
      preventing p27 degradation by the SCFskp2 pathway had no impact on tumor
      incidence or overall survival in either tumor model. Our study unveiled a
      previously unrecognized role for the control of p27 mRNA abundance in the
      development of non-small cell lung cancers. In the colon cancer model, the
      frequency of intestinal adenomas was similarly unaffected by the p27T187A
      mutation, but, unexpectedly, we found that it inhibited progression of intestinal
      adenomas to carcinomas. These studies may guide the choice of clinical settings
      in which pharmacologic inhibitors of the Skp2 pathway might be of therapeutic
      value.

PMID- 16966615
TI  - Secondary lymphoid tissue chemokine (SLC/CCL21)/CCR7 signaling regulates
      fibrocytes in renal fibrosis.
AB  - Fibrocytes are a distinct population of bloodborne cells that share markers of
      leukocytes as well as mesenchymal cells. We hypothesized that CCR7-positive
      fibrocytes migrate into the kidney in response to secondary lymphoid tissue
      chemokine (SLC/CCL21) and contribute to renal fibrosis. To investigate this
      hypothesis, renal fibrosis was induced by unilateral ureteral obstruction in
      mice. A considerable number of fibrocytes dual-positive for CD45 and type I
      collagen (ColI) or CD34 and ColI infiltrated the interstitium, reaching a peak on
      day 7. Most fibrocytes were positive for CCR7, and CCL21/CCR7 blockade reduced
      the number of infiltrating fibrocytes. CCL21 and MECA79 dual-positive vessels
      were also detected in the interstitium. The blockade of CCL21/CCR7 signaling by
      anti-CCL21 antibodies reduced renal fibrosis, which was confirmed by a decrease
      in fibrosis in CCR7-null mice with concomitant reduction in renal transcripts of
      pro alpha1 chain of ColI and TGF-beta1. The number of F4/80-positive macrophages
      decreased along with renal transcripts of monocyte chemoattractant protein 1 (MCP
      1/CCL2) after the blockade of CCL21/CCR7 signaling. These findings suggest that
      CCR7-positive fibrocytes infiltrate the kidney via CCL21-positive vessels,
      thereby contributing to the pathogenesis of renal fibrosis. Thus, the CCL21/CCR7
      signaling of fibrocytes may provide therapeutic targets for combating renal
      fibrosis.

PMID- 16966617
TI  - Dacryoadenitis associated with Acanthamoeba keratitis.
AB  - OBJECTIVE: To report the incidence of dacryoadenitis as a symptom associated with
      Acanthamoeba keratitis. METHODS: We investigated all cases of Acanthamoeba
      keratitis (20 patients and 21 eyes) diagnosed and treated at Tokyo Dental
      College, Ichikawa General Hospital, Ichikawa, Japan, between May 1, 1994, and
      November 30, 2005. We recorded the incidence of dacryoadenitis diagnosed using
      clinical signs of lacrimal gland swelling and pain on pressure, computed
      tomography, magnetic resonance imaging, and histopathologic analysis. RESULTS:
      Eight eyes (38%) of 8 patients had dacryoadenitis simultaneously with
      Acanthamoeba keratitis. Dacryoadenitis was diagnosed using histopathologic
      analysis and computed tomography in 1 patient, histopathologic analysis and
      magnetic resonance imaging in 1, magnetic resonance imaging in 2, and clinical
      signs alone in 4. Histopathologic examination in 2 patients revealed moderate
      infiltration of lymphocytes and plasma cells in the lacrimal gland compatible
      with dacryoadenitis. No Acanthamoeba organisms were found in the lacrimal gland.
      The standard protocol for Acanthamoeba keratitis was performed without particular
      treatment of dacryoadenitis in all patients. Lacrimal gland swelling improved
      after a mean of 10 weeks (range, 4-17 weeks) in conjunction with symptoms of
      keratitis; however, 1 patient (patient 1) required levator muscle surgery and
      blepharoplasty for residual ptosis. CONCLUSION: Dacryoadenitis is a clinical
      finding associated with Acanthamoeba keratitis.

PMID- 16966616
TI  - Twice-daily 0.2% brimonidine-0.5% timolol fixed-combination therapy vs
      monotherapy with timolol or brimonidine in patients with glaucoma or ocular
      hypertension: a 12-month randomized trial.
AB  - OBJECTIVE: To evaluate the intraocular pressure (IOP)-lowering efficacy and
      safety of a fixed combination of 0.2% brimonidine tartrate and 0.5% timolol
      maleate (fixed brimonidine-timolol) compared with the component medications.
      METHODS: In 2 identical, 12-month, randomized, double-masked multicenter trials,
      patients with ocular hypertension or glaucoma were treated with fixed brimonidine
      timolol twice daily (n = 385), 0.2% brimonidine tartrate 3 times daily (n = 382),
      or 0.5% timolol maleate twice daily (n = 392). MAIN OUTCOMES MEASURES: Mean
      change from baseline IOP and incidence of adverse events. RESULTS: The mean
      decrease from baseline IOP during 12-month follow-up was 4.4 to 7.6 mm Hg with
      fixed brimonidine-timolol, 2.7 to 5.5 mm Hg with brimonidine, and 3.9 to 6.2 mm
      Hg with timolol. Mean IOP reductions were significantly greater with fixed
      brimonidine-timolol compared with timolol at all measurements (P< or =.002) and
      brimonidine at 8 am, 10 am, and 3 pm (P<.001) but not at 5 pm. The incidence of
      treatment-related adverse events in the fixed-combination group was lower than
      that in the brimonidine group (P = .006) but higher than that in the timolol
      group (P<.001). The rate of discontinuation for adverse events was 14.3% with the
      fixed combination, 30.6% with brimonidine, and 5.1% with timolol. CONCLUSIONS:
      Twice-daily fixed brimonidine-timolol therapy provides sustained IOP lowering
      superior to monotherapy with either thrice-daily brimonidine or twice-daily
      timolol and is better tolerated than brimonidine but less well tolerated than
      timolol. APPLICATION TO CLINICAL PRACTICE: Fixed brimonidine-timolol is an
      effective and convenient IOP-lowering therapy.

PMID- 16966618
TI  - Idiopathic sclerosing orbital inflammation.
AB  - OBJECTIVE: To perform a multicenter review of the clinical features and treatment
      of 31 patients with idiopathic sclerosing orbital inflammation. METHODS: We
      included all patients with histologically confirmed idiopathic sclerosing orbital
      inflammation from 5 regional orbital centers. We reviewed the case notes to
      determine the clinical presentation, diagnostic features, and response to
      treatment. The main outcome measures were duration and nature of symptoms,
      anatomical location of disease, histopathological findings, treatment modalities,
      treatment efficacy and adverse effects, and final clinical status. RESULTS: We
      included 13 male and 18 female patients ranging in age from 7 to 83 years. The
      average duration of symptoms at presentation was 13.4 months. There was a
      predilection for the lateral and superior quadrants. Thirteen patients had apical
      disease, and 4 had extraorbital involvement. Histopathological findings
      invariably showed sclerosis associated with a sparse mixed cellular infiltrate.
      Twenty-seven patients were treated with oral prednisolone, response to which was
      good in 9 patients, partial in 11, and poor in 7. Six patients were treated with
      a second-line immunosuppressive agent, and 6 received radiotherapy. The response
      to radiotherapy was generally poor. CONCLUSIONS: Idiopathic sclerosing orbital
      inflammation is a rare condition that can be difficult to diagnose and manage.
      Early intervention with immunosuppression in the form of corticosteroids combined
      with second-line agents can result in control and even regression of the disease.

PMID- 16966619
TI  - Intraocular pressure variation during weight lifting.
AB  - OBJECTIVE: To evaluate the effect of weight lifting on intraocular pressure
      (IOP). METHODS: Subjects performed 4 repetitions of a bench press exercise in 2
      ways: in mode I (right eyes), the breath was held during the last repetition; in
      mode II (left eyes), subjects exhaled normally during the last repetition. The
      IOP was measured with an electronic tonometer during the fourth repetition in
      both modes while the subject sustained the exercise. RESULTS: Mean IOP during
      exercise in mode I increased by 4.3 +/- 4.2 mm Hg (P<.001, paired t test; range, 
      3.6 to 17.7 mm Hg). In mode II, mean IOP increased by 2.2 +/- 3.0 mm Hg (P<.001,
      paired t test; range, -6.0 to 8.7 mm Hg). The IOP increased in 90% of subjects in
      mode I and in 62% in mode II. An increase in IOP greater than 5.0 mm Hg was
      observed in 9 subjects (30%) in mode I and in 6 (21%) in mode II. In 2 subjects,
      IOP during exercise mode I was markedly increased (>10.0 mm Hg). CONCLUSIONS: The
      IOP increases significantly during a bench press exercise. Breath holding during
      the exercise leads to a greater IOP increase.

PMID- 16966620
TI  - Short-term treatment of cocaine and/or methamphetamine abuse with vigabatrin:
      ocular safety pilot results.
AB  - OBJECTIVE: To evaluate the ocular safety of short-term use of vigabatrin to treat
      cocaine and/or methamphetamine addiction. METHODS: Individuals who were actively
      using cocaine and/or methamphetamine were eligible for enrollment. Enrolled
      subjects were scheduled for comprehensive eye examinations at the beginning and
      end of the study. Visual field testing was performed at baseline and 1 week, 4
      weeks, 8 weeks, and 1 month or more after discontinuing vigabatrin. Twenty-eight
      subjects received at least 1 dose of vigabatrin; however, only 20 subjects
      continued beyond the initial escalating vigabatrin dose phase to the treatment
      phase. Of these 20 subjects, 18 completed the study with full follow-up. Visual
      fields were evaluated subjectively by 2 glaucoma specialists and analyzed
      objectively for group and individual changes in quadrant mean sensitivity. The
      objective analysis was also repeated for superior field quadrants after excluding
      the uppermost peripheral points to minimize the eyelid effect. The main outcome
      measures were change of visual field, visual acuity, and ocular adverse effects.
      RESULTS: Vigabatrin seemed to help treat cocaine and/or methamphetamine
      addiction. Of 18 subjects, 16 had negative test results for cocaine and
      methamphetamine use during the last 6 weeks of the trial. No ocular adverse
      events were detected. The subjective evaluation did not reveal visual field
      constriction in any of the 18 evaluable participants. Objective group and
      individual analyses for quadrant mean sensitivity did not show any change from
      baseline in any quadrant. No changes in visual acuity were noted. CONCLUSIONS: In
      this short-term pilot study, vigabatrin seemed to help treat cocaine and/or
      methamphetamine abuse. There was no evidence of ocular or visual field adverse
      effects.

PMID- 16966621
TI  - Evaluating surgical dexterity during corneal suturing.
AB  - OBJECTIVE: To evaluate motion tracking as an aid to a more objective assessment
      of ophthalmic microsurgical skill. METHODS: In a cohort study, 3 groups of
      differing levels of surgical experience were assessed. The groups included novice
      surgeons (n = 10) with fewer than 5 previously performed corneal sutures, trainee
      surgeons (n = 10) with 5 to 100 previously performed corneal sutures, and expert
      surgeons (n = 10) with more than 100 previously performed corneal sutures. The
      Imperial College Surgical Assessment Device was used for the objective assessment
      of surgical dexterity during corneal suturing. Each of the subjects used a 10-0
      nylon suture in a 3-1-1 pattern on an artificial eye (Royal College of
      Ophthalmologists, London, England). The Imperial College Surgical Assessment
      Device measures 3-dimensional spatial vectors via electromagnetic sensors
      attached to the surgeon's fingers. The number of movements, path length for the
      respective movements, and time taken to complete the given task were recorded.
      RESULTS: Highly statistically significant differences were found between the 3
      grades of surgeon experience for time taken (P<.001), number of hand movements
      (P<.001), and path length of the hand movements (P = .002) to complete the given
      task. CONCLUSIONS: Motion analysis measured by this technology may be useful in
      the formal surgical training of residents and as an objective quantitative
      measure of dexterity.

PMID- 16966622
TI  - Small molecule inhibition of HDM2 leads to p53-mediated cell death in
      retinoblastoma cells.
AB  - PURPOSE: To determine the efficacy of inducing p53-mediated cell death in
      retinoblastoma cells by Nutlin 3A, a small molecule HDM2 inhibitor. METHODS:
      Retinoblastoma cell lines WERI-RB-1 and Y79 were treated with Nutlin 3A. Cell
      viability assays, Western blot analyses, confocal microscopy, and flow cytometry
      were performed to measure cell survival, p53 protein levels, activation of
      downstream targets, and apoptosis. To determine whether the effects of Nutlin 3A
      were p53-dependent, cell viability assays were performed on Y79 cells expressing
      short interfering RNA (siRNA) against p53. RESULTS: Nutlin 3A induced cell death
      in Y79 and WERI-RB-1 in the 5- to 10-microM dose range. Treated cells
      demonstrated increased protein levels of p53 and the p53 targets p21 and HDM2.
      Phosphorylation of p53-serine-15, a marker for activation of p53 via genotoxic
      mechanisms, was absent. Y79 cells expressing siRNA against p53 demonstrated
      resistance to Nutlin 3A. CONCLUSIONS: Nutlin 3A induced p53-mediated apoptosis in
      a dose-dependent, nongenotoxic fashion in 2 retinoblastoma cell lines. CLINICAL
      RELEVANCE: Nutlin 3A is effective against retinoblastoma cells in a nongenotoxic
      manner. Because the mutagenic effects of radiation and chemotherapy may increase
      risks of secondary tumor formation, targeted p53 activation may be a safer
      alternative treatment for retinoblastoma in the future.

PMID- 16966623
TI  - Use of iris pigment epithelium to replace retinal pigment epithelium in age
      related macular degeneration: a gene expression analysis.
AB  - OBJECTIVE: To determine the gene expression profiles of primary retinal pigment
      epithelium (RPE) and iris pigment epithelium (IPE) using microarrays. METHODS:
      Primary RPE and IPE from 6 human donor eyes were collected, and total RNA was
      isolated. Differences in gene expression were determined using a human genechip
      (human U95Av2 [12 600 probes]; Affymetrix Inc, Santa Clara, Calif). RESULTS:
      Hierarchical cluster analysis differentiated the gene expression profiles of RPE
      and IPE clusters into 2 distinct groups. A mean +/- SD of 5308 +/- 416 gene
      probes were expressed in RPE vs 6130 +/- 205 in IPE. Sixty-eight genes were
      expressed only in RPE; 154 genes were expressed only in IPE. Twenty-two
      additional genes had greater than 3-fold increased expression in RPE vs IPE, and
      147 genes had greater than 3-fold decreased expression in RPE vs IPE. CONCLUSION:
      There are major differences in the gene expression profiles of primary RPE vs
      IPE. Clinical Relevance The different gene expression profiles of primary RPE vs
      IPE harvested from the same donor eyes infer that it may be difficult for IPE to
      replace all aspects of damaged RPE function in transplantation studies.

PMID- 16966624
TI  - Influence of aging on the polar and neutral lipid profiles in human meibomian
      gland secretions.
AB  - OBJECTIVE: To determine whether aging is associated with significant alterations
      in the polar and neutral lipid profiles in human meibomian gland secretions.
      METHODS: Meibomian gland secretions were collected from both eyes of younger and
      older men and women. Samples were processed for high-performance liquid
      chromatography or mass spectrometry and for the analysis of associated spectra of
      fragment ions. Subjects also underwent slitlamp evaluations of the eyelid.
      RESULTS: Aging is associated with numerous significant alterations in the lipid
      profiles of human meibomian gland secretions. Analysis of polar and neutral lipid
      patterns identified ions that were significantly different in secretions of
      younger vs older men and women, as well as ions that varied significantly only
      between men and women. Correlation coefficients within, but not between, groups
      were high. Aging was accompanied by increased opacity of meibomian gland
      secretions and by eyelid and eyelid margin changes. CONCLUSION: Aging is
      associated with significant sex-related alterations in the polar and neutral
      lipid profiles of human meibomian gland secretions. CLINICAL RELEVANCE: The
      observed changes may contribute to the age-related increase in the prevalence of
      dry eye syndromes.

PMID- 16966625
TI  - Six-year progression of retinopathy and associated risk factors in African
      American patients with type 1 diabetes mellitus: the New Jersey 725.
AB  - OBJECTIVE: To report the 6-year progression of diabetic retinopathy (DR) and
      associated risk factors among African American patients with type 1 (insulin
      dependent) diabetes mellitus. METHODS: Participants from the New Jersey 725
      included 483 African American patients with type 1 diabetes who underwent
      reexamination as part of a 6-year follow-up. Evaluations included a structured
      clinical interview, ocular examination, 7 stereoscopic fundus photographs, and
      blood pressure measurements. Severity of DR was determined via masked grading of
      fundus photographs. Biological evaluation included blood and urine assays.
      RESULTS: During the 6-year period, 56.1% of patients at risk showed progression
      of DR; 15.0% showed progression to proliferative DR; and 15.9% developed macular
      edema. A baseline high glycosylated hemoglobin level and systemic hypertension
      were significant risk factors for progression of DR, progression to proliferative
      DR, and incidence of macular edema. Progression to proliferative DR was
      significantly associated with baseline older age, renal disease, and severity of
      DR. The incidence of macular edema was significantly associated with baseline
      older age, low socioeconomic status, severity of DR, and total serum cholesterol
      level. CONCLUSIONS: Six-year progression of DR is high in African American
      patients with type 1 diabetes. Improving glycemic and blood pressure control may
      reduce the ocular morbidity of diabetes in African Americans.

PMID- 16966627
TI  - Sutureless revision of overhanging filtering blebs.
AB  - We describe methods and outcomes of a technique for sutureless surgical revision
      of symptomatic corneal overhanging filtering blebs after trabeculectomy using
      mitomycin in 6 eyes in 6 patients. Separation of the bleb from the corneal
      surface was achieved by blunt or sharp dissection, as necessary, and the
      overhanging portion of the bleb was excised and a bandage contact lens was
      inserted. Outcome measures included symptomatic relief, retention of bleb
      function, and maintenance of intraocular pressure. Five eyes (83.3%) demonstrated
      symptomatic relief and a cosmetically acceptable appearance. One patient
      continued to have dysesthesia, and 1 patient had bleb leak that required suture
      repair. Sutureless surgical revision of overhanging filtering blebs is a safe and
      effective technique to reduce bleb-related dysesthesia and improve cosmesis
      without compromising filtration function.

PMID- 16966626
TI  - Longitudinal rates of cataract surgery.
AB  - OBJECTIVE: To determine the cumulative probability of cataract surgery and
      factors accounting for such surgery. METHODS: Respondents to the Asset and Health
      Dynamics Among the Oldest Old survey, a national longitudinal panel, were
      interviewed in 1998, 2000, and 2002 to determine whether they had undergone
      cataract extraction since the previous interview (N = 8363 in 1998). Multivariate
      analysis was used to identify factors affecting cataract surgery rates. RESULTS:
      The annual incidence of cataract surgery from January 1, 1995, to December 31,
      2002, was 7.4%. The prevalence of unilateral pseudophakia increased from 7.6% in
      1998 to 9.8% in 2002; the prevalence of bilateral pseudophakia increased from
      10.5% in 1998 to 22.3% in 2002. The self-reported vision of persons undergoing
      cataract surgery improved related to that of others (a difference of 0.4 on a 9
      point scale; P<.001). Black individuals were less likely to undergo cataract
      surgery than white individuals (P<.01). The highest rates of surgery were for
      persons who were 65 years or older in 1998. However, persons with Medicare parts
      A and B coverage underwent more procedures than those with primary private
      employer-based coverage or the uninsured. CONCLUSIONS: At 5.3%, the cataract
      surgery incidence is similar to that given in previous reports. Persons
      undergoing cataract surgery more often had low self-reported vision before
      surgery, and their vision improved on average relative to others after surgery.

PMID- 16966628
TI  - Perspective on strabismus, 2006.
AB  - During the last half of the 20th century, the field of strabismus did not undergo
      as many major advances as other areas of ophthalmology. In recent years, an
      increase in basic science research has fostered important advances in our
      understanding and treatment of disorders of binocular vision. This article
      identifies 4 important questions that need to be addressed by the pediatric
      ophthalmology and adult strabismus community: (1) What terms should be used to
      describe muscle dysfunction? (2) By what mechanism does strabismus surgery work?
      (3) What is the role of orbital imaging in the management of strabismus? (4) What
      is the role of refractive surgery in the treatment of patients with amblyopia and
      strabismus?

PMID- 16966629
TI  - The role of the WDR36 gene on chromosome 5q22.1 in a large family with primary
      open-angle glaucoma mapped to this region.
AB  - OBJECTIVE: To determine whether mutations in the WD40-repeat 36 (WDR36) gene are
      responsible for primary open-angle glaucoma (POAG) that maps to the GLC1G locus
      in a family with 16 affected family members. METHODS: Ninety-two family members
      underwent clinical evaluation for POAG on the basis of intraocular pressures,
      cupping of discs, and visual fields after informed consent was obtained. All 23
      exons of WDR36 were sequenced in DNA from 5 affected and 2 unaffected family
      members. RESULTS: Sixteen family members showed evidence of POAG. A number of
      sequence variations were identified in family members; most of the variations
      were previously described single-nucleotide polymorphisms also present in the
      general population. The 3 new sequence changes were all intronic; 2 were found in
      only 1 of the family members undergoing screening. CONCLUSIONS: Several
      polymorphisms, including known single-nucleotide polymorphisms, were identified;
      however, none of these were consistent with disease-causing mutations. A mutation
      in a noncoding region of WDR36 may be responsible for POAG in this family, or
      another gene in this region may be the actual cause of glaucoma in this family.
      CLINICAL RELEVANCE: The finding that the WDR36 gene is probably not the
      responsible gene in this family further documents the genetic heterogeneity of
      POAG.

PMID- 16966630
TI  - The Armed Forces Institute of Pathology: an appreciation.

PMID- 16966631
TI  - Are we there yet? Celebrating the centennial of the Schiotz tonometer.

PMID- 16966632
TI  - Potential value of antioxidant-rich foods in slowing age-related macular
      degeneration.

PMID- 16966633
TI  - The case for observational management of suspected small choroidal melanoma.

PMID- 16966634
TI  - Treating some small melanocytic choroidal lesions without waiting for growth.

PMID- 16966635
TI  - Expression of vascular endothelial growth factor in iris melanoma.

PMID- 16966636
TI  - Localized, central optic snowflake degeneration of a polymethyl methacrylate
      intraocular lens: clinical report with pathological correlation.

PMID- 16966637
TI  - Octreotide as a treatment for uveitic cystoid macular edema.

PMID- 16966638
TI  - Keratoprosthesis in high-risk pediatric corneal transplantation: first 2 cases.

PMID- 16966639
TI  - Intravascular B-cell lymphoma (angiotropic lymphoma) with choroidal involvement.

PMID- 16966640
TI  - Unilateral eyelid swelling and ptosis caused by dural arteriovenous fistula in an
      infant.

PMID- 16966641
TI  - Vicarious menstruation in primary localized conjunctival amyloidosis.

PMID- 16966642
TI  - Vanishing disc neovascularization following intravitreal bevacizumab (avastin)
      injection.

PMID- 16966643
TI  - Pseudotumoral retinal pigment epithelium proliferation in a patient with Vogt
      Koyanagi-Harada disease.

PMID- 16966644
TI  - Adverse effects of cyclooxygenase-2 inhibitors on ocular vision.

PMID- 16966645
TI  - No evidence for the causation by cosmic radiation of nuclear cataracts in pilots.

PMID- 16966647
TI  - Editorial policy: the right to medical information.

PMID- 16966646
TI  - Further information regarding KERA and recessive cornea plana.

PMID- 16966648
TI  - "Mixed message" about public-private interface emerges from CMA.

PMID- 16966649
TI  - New Day dawns.

PMID- 16966650
TI  - Clement: set wait-times or the courts will.

PMID- 16966651
TI  - CMA wants National Children's Health Strategy.

PMID- 16966652
TI  - Advances and retreats on AIDS Front.

PMID- 16966653
TI  - MED-1: hospital on wheels.

PMID- 16966654
TI  - West Nile virus still a threat.

PMID- 16966655
TI  - Alberta doctors seek relief from oil patch boom.

PMID- 16966656
TI  - Fitness to drive.

PMID- 16966658
TI  - Online reporting of adverse reactions.

PMID- 16966657
TI  - Human T-cell lymphotropic virus type 1-associated adult T-cell leukemia/lymphoma
      in the Inuit people of Nunavut.

PMID- 16966659
TI  - An unusual cause of gastrointestinal bleeding in a young girl.

PMID- 16966660
TI  - Incidence and causes of severe neonatal hyperbilirubinemia in Canada.
AB  - BACKGROUND: Severe hyperbilirubinemia is the most common cause of neonatal
      readmission to hospital in Canada even though, in the majority of cases, risk
      factors can be identified before discharge. Severe neonatal hyperbilirubinemia
      and kernicterus continue to be reported worldwide in otherwise healthy term
      infants. We conducted this study to estimate the incidence of severe neonatal
      hyperbilirubinemia in Canada and to determine underlying causes, improved
      knowledge of which would be valuable to help identify strategies for risk
      reduction. METHODS: Data on term infants 60 days of age and younger with
      unconjugated hyperbilirubinemia were collected prospectively through the Canadian
      Paediatric Surveillance Program from 2002 to 2004. Infants were included if they
      had a peak serum total bilirubin level of more than 425 micromol/L or underwent
      an exchange transfusion. Infants with rhesus iso-immunization or who were born at
      less than 36 weeks' gestation were excluded. RESULTS: Of 367 cases reported, 258
      were confirmed to be severe neonatal hyperbilirubinemia, for an estimated
      incidence of 1 in 2480 live births. Causes were identified in 93 cases and
      included ABO incompatibility (n = 48), glucose-6-phosphate dehydrogenase
      deficiency (n = 20), other antibody incompatibility (n = 12) and hereditary
      spherocytosis (n = 7). The mean peak bilirubin level reported was 471 micromol/L
      (standard deviation [SD] 76 micromol/L, range 156-841 micromol/L). Fifty-seven
      infants (22.1%) underwent an exchange transfusion. A total of 185 infants (71.7%)
      were readmitted to hospital, 121 (65.4%) of them within 5 days of age.
      INTERPRETATION: Severe neonatal hyperbilirubinemia continues to occur frequently
      in Canada. In the majority of cases, the underlying cause was not identified. The
      high readmission rate within days after initial discharge indicates a need for a
      more thorough assessment of newborn infants and consideration of strategies to
      identify at-risk newborns, such as predischarge measurement of serum bilirubin
      levels.

PMID- 16966661
TI  - Predictors of driving cessation in mild-to-moderate dementia.
AB  - BACKGROUND: Although physicians in most provinces are mandated to report patients
      whose driving ability is impaired by illness, little is known about dementia
      related factors associated with driving cessation. The purpose of our study was
      to explore factors that may affect the likelihood of driving cessation in a
      sample of elderly, community-dwelling patients with dementia. METHODS: A 3-year
      prospective study, the Canadian Outcomes Study in Dementia (COSID) has enrolled
      883 patients with mild-to-moderate dementia at 32 centres across Canada.
      Assessment tools included the Mini-Mental State Examination (MMSE) for cognition,
      the Global Deterioration Scale (GDS) for staging (severity), the Functional
      Autonomy Measurement System (SMAF) for function, and the Neuropsychiatric
      Inventory (NPI) for behaviour. Factors associated with the decision to quit
      driving after the baseline assessment were tested with Cox survival analysis.
      RESULTS: Of 719 subjects who were or had been drivers, 203 (28.2%) were still
      driving at baseline. Over an observation period that averaged 23 months, 97
      (48.5%) of 200 patients quit driving. Factors predictive of driving cessation
      included GDS (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.15-2.45),
      MMSE score (HR 0.90, 95% CI 0.83-0.97) and NPI findings (HR 1.63 for presence of
      > or = 3 behaviours, 95% CI 1.01-2.62). Among the NPI behaviours, when they were
      analyzed separately, agitation led to a decreased likelihood of driving cessation
      (p = 0.019), whereas apathy (p = 0.031) and hallucinations (p = 0.050) led to an
      increased likelihood. INTERPRETATION: Cognitive impairment and behaviours such as
      agitation, apathy and hallucinations were significant predictors of driving
      cessation in patients with a mild to moderate degree of dementia. These findings
      should be considered when one counsels patients and their families.

PMID- 16966662
TI  - Surveillance of severe neonatal hyperbilirubinemia: a view from south of the
      border.

PMID- 16966663
TI  - Driving retirement: the role of the physician.

PMID- 16966664
TI  - Understanding the health of Indigenous peoples in Canada: key methodological and
      conceptual challenges.

PMID- 16966665
TI  - Health literacy: where are the Canadian doctors?

PMID- 16966667
TI  - End-of-life care in Canada.

PMID- 16966666
TI  - Natriuretic peptides in the diagnosis and management of heart failure.
AB  - The natriuretic peptides are a family of related hormones that play a crucial
      role in cardiovascular homeostasis. They have recently emerged as potentially
      important clinical markers in heart failure. Recent data have suggested an
      important role for these markers in establishing the diagnosis of heart failure
      in patients with unexplained dyspnea in both acute care and ambulatory settings.
      Other clinical uses of the natriuretic peptides, such as screening for
      asymptomatic ventricular dysfunction, establishing prognosis or guiding titration
      of drug therapy, are under investigation but have not yet sufficiently been
      validated for widespread clinical use.

PMID- 16966668
TI  - Patient safety deserves better response.

PMID- 16966670
TI  - End-of-life care in Canada.

PMID- 16966672
TI  - Terri Schiavo: rest in peace.

PMID- 16966673
TI  - Terri Schiavo: rest in peace.

PMID- 16966674
TI  - Terri Schiavo: rest in peace.

PMID- 16966675
TI  - Introduction: rethinking child care research.
AB  - This introduction summarizes the articles in this collection. It describes how
      the articles address one or more of the key elements of the child care research
      model: (a) selecting and measuring the independent variablesto determine the
      characteristics ("qualities") of the child care environment (and, in some
      studies, the characteristics of parents and family), (b) selecting and measuring
      the dependent variablesto determine the child's physical and developmental status
      after a period of time in a particular child care arrangement (usually a school
      year) compared with that of children in other arrangements (or simply the same
      child before spending time in the arrangement), (c) establishing causal
      linksbetween the independent and dependent variables that are either assumed in
      randomized experiments or estimated through statistical controls in
      nonexperimental studies, and (d) assessing impacts across subgroups to see
      whether the program benefits one particular group more (or less) than others. The
      collection closes with a proposal to develop a systematic federal research
      program to pursue improvements in child care and early childhood education
      programs.

PMID- 16966676
TI  - The "quality " of early care and education settings: definitional and measurement
      issues.
AB  - There is a widespread belief that high-quality early care and education can
      improve children's school readiness. However, debate continues about the
      essential elements of a high-quality experience, about whether quality means the
      same things across different types of care settings, about how to measure
      quality, and about the level of quality that might make a meaningful difference
      in outcomes for children. Are the aspects of the child care environment that
      researchers measure the ones that are most strongly related to children's
      development? This article argues that the ways in which researchers currently
      measure early care environments are flawed and that the conclusions drawn about
      the relationship between these measures and outcomes for children are frequently
      incorrect or overstated. The article addresses four questions: How is the quality
      of the child care environment commonly defined and measured? Do the most commonly
      used measures capture the child's experience? Do they work well across all
      settings? Are researchers drawing the correct conclusions from studies that
      relate the child care environment to child outcomes? Finally, the article
      discusses some possible directions for future research.

PMID- 16966677
TI  - Child outcome measures in the study of child care quality.
AB  - This article assesses whether there are methodological problems with child
      outcome measures that may contribute to the small associations between child care
      quality and child outcomes found in the literature. Outcome measures used in 65
      studies of child care quality published between 1979 and December 2005 were
      examined, taking the previous review by Vandell and Wolfe (2000) as the starting
      point. Serious methodological problems were not pervasive for child outcome
      measures. However, methodological concerns were most prevalent among measures of
      socioemotional development. Furthermore, psychometric information on outcome
      measures was often missing from published reports, and health outcomes and
      approaches to learning were infrequently studied. Future research should address
      alignment issues between aspects of quality and the specific child outcomes
      chosen for study.

PMID- 16966678
TI  - Connecting child care quality to child outcomes: drawing policy lessons from
      nonexperimental data.
AB  - Effective early childhood intervention and child care policies should be based on
      an understanding of the effects of child care quality and type on child well
      being. This article describes methods for securing unbiased estimates of these
      effects from nonexperimental data. It focuses on longitudinal studies like the
      one developed by the National Institute of Child Health and Human Development's
      Early Child Care Research Network. This article first describes bias problems
      that arise in analyses of nonexperimental data and then explains strategies for
      controlling for biases arising from parental selection of child care. Next, it
      comments on attrition in longitudinal studies and outlines some strategies for
      addressing possible attrition bias. Finally, it discusses the need to translate
      "effect sizes" derived from these studies into the kinds of cost and benefit
      information needed by policy makers.

PMID- 16966679
TI  - Family factors in child care research.
AB  - The purpose of this article is to review evidence concerning the joint impact of
      family characteristics and child care experiences in understanding children's
      development. Although child care experiences are related to children's
      development across a variety of domains, family characteristics, particularly
      socioeconomic status and parenting quality, are typically stronger predictors of
      children's outcomes. An important implication of these findings is that high
      quality child care experiences are likely to have stronger effects on children
      who are at risk of poorer outcomes because of less optimal family environments;
      evidence from experimental and nonexperimental studies generally supports this
      conclusion. From a policy perspective, an important goal for future research is
      to identify subgroups of families within the heterogeneous low-income population
      that are in particular need of relatively more intensive services and to develop
      effective interventions that are tailored to their needs.

PMID- 16966680
TI  - Randomize groups, not individuals: a strategy for improving early childhood
      programs.
AB  - Until the past few years, our nation's approach to designing federal programs for
      preschool-age children lacked coherence and paid little attention to what had
      worked (and not worked) in the past. In this article, the authors propose that
      credible information useful for designing effective programs will require the
      ongoing, systematic development and evaluation of alternative approaches for the
      improvement of large-scale early childhood programs. The research should place
      greater reliance on experiments in which existing groups of individuals, such as
      intact classes or preschool agencies, are randomly assigned to implement
      competing early education programs or program components. Randomizing groups,
      rather than individual children, changes the research question from "What works?"
      to "What works better?" yielding more useful information than is currently
      available about which preschool approaches ought to be strongly embedded in our
      nation's social policy.

PMID- 16966681
TI  - The Parkinson disease gene LRRK2: evolutionary and structural insights.
AB  - Mutations in the human leucine-rich repeat kinase 2 (LRRK2) gene are associated
      with both familial and sporadic Parkinson disease (PD). LRRK2 belongs to a gene
      family known as Roco. Roco genes encode for large proteins with several protein
      domains. Particularly, all Roco proteins have a characteristic GTPase domain,
      named Roc, plus a domain of unknown function called COR. In addition, LRRK2 and
      several other Roco proteins also contain a protein kinase domain. In this study,
      I use a combination of phylogenetic and structural analyses of the COR, Roc, and
      kinase domains present in Roco proteins to describe the origin and evolutionary
      history of LRRK2. Phylogenetic analyses using these domains demonstrate that
      LRRK2 emerged from a duplication that occurred after the protostome-deuterostome
      split. The duplication was followed by the acquisition by LRRK2 proteins of a
      specific type of N-terminal repeat, described here for the first time. This
      repeat is absent in the proteins encoded by the paralogs of LRRK2, called LRRK1
      or in protostome LRRK proteins. These results suggest that Drosophila or
      Caenorhabditis LRRK genes may not be good models to understand human LRRK2
      function. Genes in the slime mold Dictyostelium discoideum with structures very
      similar to those found in animal LRRK genes, including the protein kinase domain,
      have been described. However, phylogenetic analyses suggest that this structural
      similarity is due to independent acquisitions of distantly related protein kinase
      domains. Finally, I confirm in an extensive sequence analysis that the Roc GTPase
      domain is related but still substantially different from small GTPases, such as
      Rab, Ras, or Rho. Modeling based on known kinase structures suggests that
      mutations in LRRK2 that cause familiar PD may alter the local 3-dimensional
      folding of the LRRK2 protein without affecting its overall structure.

PMID- 16966682
TI  - Gene gain and gene loss in streptococcus: is it driven by habitat?
AB  - Bacterial genomes can evolve either by gene gain, gene loss, mutating existing
      genes, and/or by duplication of existing genes. Recent studies have clearly
      demonstrated that the acquisition of new genes by lateral gene transfer (LGT) is
      a predominant force in bacterial evolution. To better understand the significance
      of LGT, we employed a comparative genomics approach to model species-specific and
      intraspecies gene insertions/deletions (ins/del among 12 sequenced streptococcal
      genomes using a maximum likelihood method. This study indicates that the rate of
      gene ins/del is higher on the external branches and varies dramatically for each
      species. We have analyzed here some of the experimentally characterized species
      specific genes that have been acquired by LGT and conclude that at least a
      portion of these genes have a role in adaptation.

PMID- 16966683
TI  - Reaching first base in the treatment of metastatic melanoma.

PMID- 16966684
TI  - Metabolic imaging predicts response, survival, and recurrence in adenocarcinomas
      of the esophagogastric junction.
AB  - PURPOSE: A previous study suggested that measurement of therapy-induced changes
      in tumor glucose metabolism by positron emission tomography (PET) with the
      glucose analog [18F]fluorodeoxyglucose (FDG) allows to select patients most
      likely to benefit from preoperative chemotherapy in adenocarcinomas of the
      esophagogastric junction (AEG). The aim of this study was to prospectively
      validate these findings by using an a priori definition of metabolic response.
      PATIENTS AND METHODS: Sixty-five patients with locally advanced AEGs were
      included. Tumor glucose utilization was quantitatively assessed by FDG-PET before
      chemotherapy and 14 days after initiation of therapy. Patients were classified as
      metabolic responders when the metabolic activity of the primary tumor had
      decreased by more than 35% at the time of the second PET. RESULTS: Metabolic
      responders showed a high histopathologic response rate (44%) with a 3-year
      survival rate of 70%. In contrast, prognosis was poor for metabolic nonresponders
      with a histopathologic response rate of 5% (P = .001) and a 3-year survival rate
      of 35% (P = .01). A multivariate analysis (covariates: ypT-, ypN-category,
      histopathologic response) demonstrated that metabolic response was the only
      factor predicting recurrence (P = .018) in the subgroup of completely resected
      (R0) patients. CONCLUSION: This study prospectively demonstrates that changes in
      tumor metabolic activity during chemotherapy predict response, prognosis, and
      recurrence. These data provide the basis for clinical trials in which
      preoperative treatment is changed for patients without a metabolic response early
      in the course of therapy. PET-guided induction therapy may even be applicable to
      earlier tumor stages because surgery is only minimally delayed in nonresponding
      patients.

PMID- 16966685
TI  - Detection of subclinical systemic disease in primary CNS lymphoma by polymerase
      chain reaction of the rearranged immunoglobulin heavy-chain genes.
AB  - PURPOSE: To search for subclinical systemic disease in bone marrow and peripheral
      blood in patients with primary CNS lymphoma (PCNSL) to elucidate whether
      extracerebral relapse may represent a sequel of initial occult systemic disease
      rather than true extracerebral spread. PATIENTS AND METHODS: Bone marrow and
      peripheral-blood specimens of 24 PCNSL patients were examined using polymerase
      chain reaction (PCR) for analysis of clonally rearranged immunoglobulin heavy
      chain (IgH) genes. RESULTS: Identical dominant PCR products were found in bone
      marrow aspirates, blood samples, and tumor biopsy specimens of two patients,
      indicating that the same tumor cell population is present in the CNS and in
      extracerebral sites. Follow-up IgH PCR performed in one of these patients in
      complete remission 24 months after diagnosis yielded a persistent monoclonal
      product in the blood. An oligoclonal IgH rearrangement pattern was found in the
      tumor specimen of two other patients, whereas bone marrow and blood samples
      demonstrated the same dominant PCR products. Follow-up PCR showed a persistent
      monoclonal amplificate in blood in one of these patients 27 months after
      diagnosis. CONCLUSION: It could be demonstrated for the first time that
      subclinical systemic disease can be present in PCNSL patients at initial
      diagnosis. Our findings may have an impact on the understanding of PCNSL
      pathogenesis and the extent of staging and treatment.

PMID- 16966686
TI  - RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non
      small-cell lung cancer.
AB  - PURPOSE: RRM1 encodes the regulatory subunit of ribonucleotide reductase and is a
      molecular target of gemcitabine. Previous studies showed increased RRM1
      expression on continuous exposure of cell lines to gemcitabine and suggested
      improved survival for patients with low as opposed to high tumoral RRM1
      expression when treated with gemcitabine-containing chemotherapy. However, the
      principal hypothesis that intratumoral levels of gene expression are associated
      with disease response has not been addressed. PATIENTS AND METHODS: We
      constructed genetically modified lung cancer cell lines with increased and
      decreased RRM1 expression to investigate the in vitro 50% inhibitory
      concentration (IC50) for gemcitabine, cisplatin, and carboplatin. A prospective
      phase II clinical trial in patients with locally advanced non-small-cell lung
      cancer was conducted with pretreatment tumor collection for determination of RRM1
      and ERCC1 expression by real-time reverse transcriptase polymerase chain
      reaction. The levels of gene expression were correlated with tumor response after
      two cycles of gemcitabine and carboplatin. RESULTS: In cell lines with a
      genetically engineered 15-fold RRM1 expression range, the gemcitabine IC50 had a
      100-fold range, and the cisplatin and carboplatin IC50 had a two-fold range. They
      were highest in constructs with high RRM1 expression. In the prospective clinical
      trial, RRM1 expression was significantly (P = .002) and inversely correlated (r =
      -0.498) with disease response. ERCC1 expression showed a similar trend (P =
      .099). CONCLUSION: The results strongly suggest that tumoral RRM1 expression is a
      major predictor of disease response to gemcitabine/platinum chemotherapy. ERCC1
      expression is predictive of response albeit to a lesser degree.

PMID- 16966687
TI  - Gemcitabine plus carboplatin compared with carboplatin in patients with platinum
      sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC
      CTG, and the EORTC GCG.
AB  - PURPOSE: Most patients with advanced ovarian cancer develop recurrent disease.
      For those patients who recur at least 6 months after initial therapy, paclitaxel
      platinum has shown a modest survival advantage over platinum without paclitaxel;
      however, many patients develop clinically relevant neurotoxicity, frequently
      resulting in treatment discontinuation. Thus, an alternative regimen without
      significant neurotoxicity was evaluated by comparing gemcitabine plus carboplatin
      with single-agent carboplatin in platinum-sensitive recurrent ovarian cancer
      patients. METHODS: Patients with platinum-sensitive recurrent ovarian cancer were
      randomly assigned to receive either gemcitabine plus carboplatin or carboplatin
      alone, every 21 days. The primary objective was to compare progression-free
      survival (PFS). RESULTS: Three hundred fifty-six patients (178 gemcitabine plus
      carboplatin; 178 carboplatin) were randomly assigned. Patients received a median
      of six cycles in both arms. With a median follow-up of 17 months, median PFS was
      8.6 months (95% CI, 7.9 to 9.7 months) for gemcitabine plus carboplatin and 5.8
      months (95% CI, 5.2 to 7.1 months) for carboplatin. The hazard ration (HR) for
      PFS was 0.72 (95% CI, 0.58 to 0.90; P = .0031). Response rate was 47.2% (95% CI,
      39.9% to 54.5%) for gemcitabine plus carboplatin and 30.9% (95% CI, 24.1% to
      37.7%) for carboplatin (P = .0016). The HR for overall survival was 0.96 (95% CI,
      0.75 to1.23; P = .7349). While myelosuppression was significantly more common in
      the combination, sequelae such as febrile neutropenia or infections were
      uncommon. No statistically significant differences in quality of life scores
      between arms were noted. CONCLUSION: Gemcitabine plus carboplatin significantly
      improves PFS and response rate without worsening quality of life for patients
      with platinum-sensitive recurrent ovarian cancer.

PMID- 16966688
TI  - Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced
      melanoma: the Oblimersen Melanoma Study Group.
AB  - PURPOSE: Chemotherapy resistance in melanoma has been linked to antiapoptotic
      effects mediated by Bcl-2 protein. We evaluated whether targeting Bcl-2 using an
      antisense oligonucleotide (oblimersen sodium) could improve the efficacy of
      systemic chemotherapy in patients with advanced melanoma. PATIENTS AND METHODS:
      We randomly assigned chemotherapy-naive patients with advanced melanoma to
      treatment with dacarbazine (1,000 mg/m2) alone or preceded by a 5-day continuous
      intravenous infusion of oblimersen sodium (7 mg/kg/d) every 3 weeks for up to
      eight cycles. Patients were stratified by Eastern Cooperative Oncology Group
      performance status, liver metastases, disease site, and serum lactate
      dehydrogenase (LDH). The primary efficacy end point was overall survival.
      RESULTS: Among 771 patients randomly assigned, the addition of oblimersen to
      dacarbazine yielded a trend toward improved survival at 24-month minimum follow
      up (median, 9.0 v 7.8 months; P = .077) and significant increases in progression
      free survival (median, 2.6 v 1.6 months; P < .001), overall response (13.5% v
      7.5%; P = .007), complete response (2.8% v 0.8%), and durable response (7.3% v
      3.6%; P = .03). A significant interaction between baseline serum LDH and
      treatment was observed; oblimersen significantly increased survival in patients
      whose baseline serum LDH was not elevated (median overall survival, 11.4 v 9.7
      months; P = .02). Neutropenia and thrombocytopenia were increased in the
      oblimersen-dacarbazine group; however, there was no increase in serious
      infections or bleeding events. CONCLUSION: The addition of oblimersen to
      dacarbazine significantly improved multiple clinical outcomes in patients with
      advanced melanoma and increased overall survival in patients without an elevated
      baseline serum LDH.

PMID- 16966689
TI  - Loss of heterozygosity 1p36 and 19q13 is a prognostic factor for overall survival
      in patients with diffuse WHO grade 2 gliomas treated without chemotherapy.
AB  - PURPOSE: This study was conducted to elucidate the impact of loss of
      heterozygosity (LOH) for chromosomes 1p36 and 19q13 on the overall survival of
      patients with diffusely infiltrating WHO grade 2 gliomas treated without
      chemotherapy. PATIENTS AND METHODS: We assessed the LOH status of tumors from
      patients harboring WHO grade 2 gliomas diagnosed between 1991 and 2000. Patients
      were either followed after initial biopsy or treated by surgery and/or radiation
      therapy (RT). Overall survival, time to malignant transformation, and progression
      free survival were last updated as of March 2005. RESULTS: Of a total of 79
      patients, LOH 1p36 and LOH 19q13 could be assessed in 67 and 66 patients,
      respectively. The median follow-up after diagnosis was 6 years. Loss of either 1p
      or 19q, in particular codeletion(s) at both loci, was found to positively impact
      on both overall survival (log-rank P < .01), progression-free survival, and
      survival without malignant transformation (P < .05). Tumor volume (P < .0001),
      neurologic deficits at diagnosis (P < .01), involvement of more than one lobe (P
      < .01), and absence of an oligodendroglial component (P < .05) were also
      predictors of shorter overall survival. The extent of surgery was similar in
      patients with or without LOH 1p and/or 19q; RT was more frequently resorted to
      for patients without than for patients with LOH 1p/19q (30% v 60%). CONCLUSION:
      The presence of LOH on either 1p36 or 19q13, and in particular codeletion of both
      loci is a strong, nontreatment-related, prognostic factor for overall survival in
      patients with diffusely infiltrating WHO grade 2 gliomas.

PMID- 16966690
TI  - Phase II study of belagenpumatucel-L, a transforming growth factor beta-2
      antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung
      cancer.
AB  - PURPOSE: Belagenpumatucel-L is a nonviral gene-based allogeneic tumor cell
      vaccine that demonstrates enhancement of tumor antigen recognition as a result of
      transforming growth factor beta-2 inhibition. PATIENTS AND METHODS: We performed
      a randomized, dose-variable, phase II trial involving stages II, IIIA, IIIB, and
      IV non-small-cell lung cancer patients. Each patient received one of three doses
      (1.25, 2.5, or 5.0 x 10(7) cells/injection) of belagenpumatucel-L on a monthly or
      every other month schedule to a maximum of 16 injections. Immune function,
      safety, and anticancer activity were monitored. RESULTS: Seventy-five patients
      (two stage II, 12 stage IIIA, 15 stage IIIB, and 46 stage IV patients) received a
      total of 550 vaccinations. No significant adverse events were observed. A dose
      related survival difference was demonstrated in patients who received > or = 2.5
      x 10(7) cells/injection (P = .0069). Focusing on the 61 late-stage (IIIB and IV)
      assessable patients, a 15% partial response rate was achieved. The estimated
      probabilities of surviving 1 and 2 years were 68% and 52%, respectively for the
      higher dose groups combined and 39% and 20%, respectively, for the low-dose
      group. Immune function was explored in the 61 advanced-stage (IIIB and IV)
      patients. Increased cytokine production (at week 12 compared with patients with
      progressive disease) was observed among clinical responders (interferon gamma, P
      = .006; interleukin [IL] -6, P = .004; IL-4, P = .007), who also displayed an
      elevated antibody-mediated response to vaccine HLAs (P = .014). Furthermore,
      positive enzyme-linked immunospot reactions to belagenpumatucel-L showed a
      correlation trend (P = .086) with clinical responsiveness in patients achieving
      stable disease or better. CONCLUSION: Belagenpumatucel-L is well tolerated, and
      the survival advantage justifies further phase III evaluation.

PMID- 16966691
TI  - MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are
      associated with distinctive pathologic features and clinical behavior.
AB  - PURPOSE: We investigated the global microRNA expression patterns in normal
      pancreas, pancreatic endocrine tumors and acinar carcinomas to evaluate their
      involvement in transformation and malignant progression of these tumor types.
      MicroRNAs are small noncoding RNAs that regulate gene expression by targeting
      specific mRNAs for degradation or translation inhibition. Recent evidence
      indicates that microRNAs can contribute to tumor development and progression and
      may have diagnostic and prognostic value in several human malignancies. MATERIALS
      AND METHODS: Using a custom microarray, we studied the global microRNA expression
      in 12 nontumor pancreas and 44 pancreatic primary tumors, including 12
      insulinomas, 28 nonfunctioning endocrine tumors, and four acinar carcinomas.
      RESULTS: Our data showed that a common pattern of microRNA expression
      distinguishes any tumor type from normal pancreas, suggesting that this set of
      microRNAs might be involved in pancreatic tumorigenesis; the expression of miR
      103 and miR-107, associated with lack of expression of miR-155, discriminates
      tumors from normal; a set of 10 microRNAs distinguishes endocrine from acinar
      tumors and is possibly associated with either normal endocrine differentiation or
      endocrine tumorigenesis; miR-204 is primarily expressed in insulinomas and
      correlates with immunohistochemical expression of insulin; and the overexpression
      of miR-21 is strongly associated with both a high Ki67 proliferation index and
      presence of liver metastasis. CONCLUSION: These results suggest that alteration
      in microRNA expression is related to endocrine and acinar neoplastic
      transformation and progression of malignancy, and might prove useful in
      distinguishing tumors with different clinical behavior.

PMID- 16966692
TI  - Stage II colon cancer prognosis prediction by tumor gene expression profiling.
AB  - PURPOSE: This study mainly aimed to identify and assess the performance of a
      microarray-based prognosis predictor (PP) for stage II colon cancer. A previously
      suggested 23-gene prognosis signature (PS) was also evaluated. PATIENTS AND
      METHODS: Tumor mRNA samples from 50 patients were profiled using oligonucleotide
      microarrays. PPs were built and assessed by random divisions of patients into
      training and validation sets (TSs and VSs, respectively). For each TS/VS split, a
      30-gene PP, identified on the TS by selecting the 30 most differentially
      expressed genes and applying diagonal linear discriminant analysis, was used to
      predict the prognoses of VS patients. Two schemes were considered: single-split
      validation, based on a single random split of patients into two groups of equal
      size (group 1 and group 2), and Monte Carlo cross validation (MCCV), whereby
      patients were repeatedly and randomly divided into TS and VS of various sizes.
      RESULTS: The 30-gene PP, identified from group 1 patients, yielded an 80%
      prognosis prediction accuracy on group 2 patients. MCCV yielded the following
      average prognosis prediction performance measures: 76.3% accuracy, 85.1%
      sensitivity, and 67.5% specificity. Improvements in prognosis prediction were
      observed with increasing TS size. The 30-gene PS were found to be highly-variable
      across TS/VS splits. Assessed on the same random splits of patients, the
      previously suggested 23-gene PS yielded a 67.7% mean prognosis prediction
      accuracy. CONCLUSION: Microarray gene expression profiling is able to predict the
      prognosis of stage II colon cancer patients. The present study also illustrates
      the usefulness of resampling techniques for honest performance assessment of
      microarray-based PPs.

PMID- 16966694
TI  - Drinking from the fountain of promise: biomarkers in the surveillance of
      Barrett's oesophagus--the glass is half full!

PMID- 16966693
TI  - Endocannabinoid overactivity and intestinal inflammation.
AB  - Cannabinoid receptors of type 1 and 2 (CB(1) and CB(2)), endogenous ligands that
      activate them (endocannabinoids), and mechanisms for endocannabinoid biosynthesis
      and inactivation have been identified in the gastrointestinal system. Activation
      of CB(1 )receptors by endocannabinoids produces relaxation of the lower
      oesophageal sphincter and inhibition of gastric acid secretion, intestinal
      motility, and fluid stimulated secretion. However, stimulation of cannabinoid
      receptors impacts on gastrointestinal functions in several other ways. Recent
      data indicate that the endocannabinoid system in the small intestine and colon
      becomes over stimulated during inflammation in both animal models and human
      inflammatory disorders. The pathological significance of this "endocannabinoid
      overactivity" and its possible exploitation for therapeutic purposes are
      discussed here.

PMID- 16966695
TI  - Impedance-pH monitoring in proton pump inhibitor resistant patients: ready for
      clinical application?

PMID- 16966696
TI  - Hypnosis for non-cardiac chest pain.

PMID- 16966697
TI  - Another important function for an old friend! The role of iron in colorectal
      carcinogenesis.

PMID- 16966698
TI  - Folate: a magic bullet or a double edged sword for colorectal cancer prevention?

PMID- 16966699
TI  - An unusual cause of rectal bleeding.

PMID- 16966700
TI  - Weight loss and an abdominal mass after resection of a lung carcinoma.

PMID- 16966701
TI  - Narrow band imaging with magnification for dysplasia detection and pit pattern
      assessment in ulcerative colitis surveillance: a case with multiple dysplasia
      associated lesions or masses.
AB  - A 62 year old man with longstanding ulcerative colitis and previous endoscopic
      excision of two dysplasia associated lesions or masses (DALMs) was admitted to
      our endoscopy unit for evaluation and resection of other possible DALMs. He had
      previously been offered and refused colectomy because of comorbidity from
      Parkinson's disease. He had multiple polypoid and sessile lesions which were
      assessed using a third generation prototype narrow band imaging (NBI) colonoscope
      with magnification. Selected lesions were either biopsied or resected with a
      combination of endoscopic submucosal dissection and endoscopic mucosal resection
      techniques. We correlated the pit pattern and vascular pattern intensity seen
      with magnification NBI with histology of both inflammatory and dysplastic
      lesions. Dysplastic areas showed Kudo pit patterns II, IIIL, and IV and high
      vascular pattern intensity. Non-dysplastic and dysplastic areas of recurrence
      immediately adjacent to the scar from a previous endoscopic mucosal resection
      site were also assessed. This is the first case report where NBI has been shown
      to help in DALM detection and to distinguish dysplastic from non-dysplastic
      mucosa in ulcerative colitis.

PMID- 16966702
TI  - Unusual findings in the biliary tract.

PMID- 16966703
TI  - A case of a "fragile" oesophagus.

PMID- 16966705
TI  - Alterations in intestinal permeability.

PMID- 16966706
TI  - Long term suppressive therapy with pegylated interferon for chronic hepatitis C
      associated membranoproliferative glomerulonephritis.

PMID- 16966707
TI  - Diagnosis of lymphogranuloma venereum from biopsy samples.

PMID- 16966708
TI  - Efficacy of ecabet sodium enema on steroid resistant or steroid dependent
      ulcerative colitis.

PMID- 16966704
TI  - Antiangiogenic therapy in human gastrointestinal malignancies.

PMID- 16966709
TI  - Anti-TNF-alpha therapy for orofacial granulomatosis: proceed with caution.

PMID- 16966710
TI  - EUS could detect ascites missed by CT scan.

PMID- 16966711
TI  - Adverse events in clinical trials with azathioprine and mesalamine for prevention
      of postoperative recurrence of Crohn's disease.

PMID- 16966712
TI  - Impaired portal circulation resulting from L-arginine deficiency in patients with
      lysinuric protein intolerance.

PMID- 16966713
TI  - Association study of TNFSF15 polymorphisms in Japanese patients with inflammatory
      bowel disease.

PMID- 16966714
TI  - Biotech drugs come of age; policymakers take notice.

PMID- 16966715
TI  - Insurance coverage of biopharmaceuticals.

PMID- 16966716
TI  - Insurers' strategies for managing the use and cost of biopharmaceuticals.
AB  - This paper examines strategies under development by health insurers to manage
      biopharmaceuticals, as their use spreads beyond rare diseases and academic sub
      specialists to common conditions and community-based practices. Emphasis is
      placed on medical management (formulary placement and prior authorization),
      network design (physician contracting and drug distribution), and benefit design
      (coinsurance and annual payment limits). Contemporary initiatives are modest in
      ambition but potentially lay the foundation for a framework that balances access
      to innovation with affordability in this dynamic industry.

PMID- 16966717
TI  - Coverage options for promising technologies: Medicare's 'coverage with evidence
      development'.
AB  - In April 2005 the Centers for Medicare and Medicaid Services (CMS) posted on its
      Web site a draft guidance document describing a new approach to coverage policy
      called "coverage with evidence development" (CED). CED offered an option for
      coverage of promising drugs, biologics, devices, diagnostics, and procedures that
      would not otherwise meet Medicare's evidentiary standards for being "reasonable
      and necessary." An updated guidance was posted 12 July 2006, clarifying several
      key statutory, regulatory, and operational issues. This paper traces the history
      of this policy approach, explains the rationale behind the policy, and describes
      the major challenges that will need to be addressed for CED to become an
      important advance in evidence-based coverage decision making.

PMID- 16966718
TI  - Medicare's coverage of colorectal cancer drugs: a case study in evidence
      development and policy.
AB  - Payers point to the lack of unbiased evidence for making coverage decisions for
      new and often costly technologies. This paper provides a case study of a new
      approach to developing information to meet the needs of a payer: Medicare's
      coverage with evidence development (CED) policy. Medicare's decision to condition
      coverage of cancer therapies on clinical trial participation is an early
      application of CED and signals Medicare's interest in developing evidence on new
      technologies for beneficiaries. This paper reviews the rationale and challenges
      Medicare faces in applying its CED policy and discusses the implications of
      payers' using and generating evidence.

PMID- 16966719
TI  - Access to cancer drugs in Medicare Part D: formulary placement and beneficiary
      cost sharing in 2006.
AB  - The Medicare Part D benefit expands the universe of cancer drugs and biologics
      that Medicare may cover. Individual Part D plans have discretion to determine
      their formularies and cost sharing for drugs within federal guidelines. This
      paper analyzes differences in coverage and cost sharing for cancer drugs among
      these plans. We find that many cancer drugs, including brand-name products, are
      covered by almost all plans, although prior authorization might limit access to
      some. In addition, many plans charge a relatively low copayment for most cancer
      drugs. These findings suggest that Part D could greatly expand beneficiaries'
      access to cancer treatments.

PMID- 16966720
TI  - Translating epoetin research into practice: the role of government and the use of
      scientific evidence.
AB  - Spending for epoetin is Medicare's single largest drug expenditure. We chronicle
      the evolution of epoetin policy based on a lack of well-designed post-Food and
      Drug Administration approval studies demonstrating clinical benefit;
      congressional/federal agency reliance on clinical practice guidelines that might
      have misinterpreted evidence supporting causality; and the premature translation
      of research into practice and policy. Were the right choices made? Epoetin
      showcases the risk and benefit conundrum created when evidentiary standards are
      relaxed. Our review concludes with broad-based policy recommendations for the
      newly implemented Medicare Part D program.

PMID- 16966721
TI  - Biotechnology and Medicare's new technology policy: lessons from three case
      studies.
AB  - Biotechnology has figured prominently in recent Medicare coverage and payment
      policies. Biotech treatments push policy boundaries for several reasons: They
      attract strong patient demand; they often treat rare or life-threatening
      diseases; they may have uncertain evidence of health benefits; and they are often
      costly. This paper considers case studies of Medicare coverage for off-label uses
      of biotech cancer drugs and payments for anemia biopharmaceuticals. The cases
      suggest Medicare's ongoing challenge to balance access considerations, the role
      and strength of evidence, and cost consequences of new treatments.

PMID- 16966722
TI  - Evolution and future of biopharmaceuticals.

PMID- 16966723
TI  - The intersection of biotechnology and pharmacogenomics: health policy
      implications.
AB  - Increasing knowledge of the genetic basis of disease is changing the landscape of
      health care. Two critical aspects are growth in biotechnology and growth in
      personalized health care, particularly targeting medicines based on genetic
      information (pharmacogenomics). This paper provides an overview of the health
      policy implications of the integration of biotechnology and pharmacogenomics. I
      examine four factors that determine whether relevant technologies will be
      successfully adopted, using case studies for illustration. Key policy challenges
      include determining the appropriate role of policy in (1) providing incentives to
      develop socially beneficial interventions and (2) facilitating development of the
      evidence base.

PMID- 16966724
TI  - Linking pharmacogenetics-based diagnostics and drugs for personalized medicine.
AB  - Progress toward personalized medicine in the five years following the sequencing
      of the human genome has been slower than many expected. We focus on two potential
      factors that might be important in explaining this disappointing progress: the
      limitations of genetic prediction and the lack of appropriate economic
      incentives. Clinical application of DNA-based and other biomarkers is likely to
      succeed only on a case-by-case basis, depending on such factors as information
      content of the biomarker, accuracy of current assessment methods, and
      effectiveness of available interventions. Both strong intellectual property and
      value-based, flexible pricing systems will be important in making personalized
      medicine a reality.

PMID- 16966725
TI  - The market for follow-on biologics: how will it evolve?
AB  - With spending on biologics rising and patent expiry approaching for several
      blockbuster biologics, Congress and the Food and Drug Administration are
      considering creating a clear pathway for so-called follow-on biologics.
      Differences between drugs and biologics will affect market outcomes in various
      ways. Conservative budget impacts are appropriate in the short run because fewer
      competitors will enter, and average prices will drop less than was the case
      following the Hatch-Waxman Act. Over the long term, intellectual property
      provisions will be important considerations for policymakers designing a pathway
      for follow-on biologics that balances price competition and innovation
      incentives.

PMID- 16966726
TI  - The emerging market dynamics of targeted therapeutics.
AB  - Targeted biotech drugs that attack specific biological molecules that cause
      disease are bringing new benefits even as they foment pricing dynamics that are
      very different from those of traditional drugs. Targeted drugs tend not to
      compete with each other even when treating closely related diseases, which makes
      them resistant to price controls. We can expect the supply of expensive new so
      called biotech drugs to continue. But the same properties that generate premium
      prices also facilitate inventing around successful drugs, eventually leading to
      vigorous competition despite the lack of generic alternatives.

PMID- 16966727
TI  - How changes in drug-safety regulations affect the way drug and biotech companies
      invest in innovation.
AB  - Changes in the economics of product development resulting from heightened safety
      regulations could have a sizable negative impact on drug and biotechnology
      companies' decisions about investing in innovation. We developed a model to
      compare the potential economic effects of pre- and postmarketing strategies to
      identify safety problems with new drugs. Although expanding Phase III clinical
      testing and postmarketing safety surveillance are not perfect substitutes, our
      findings suggest that even a large increase in funding for the latter will have a
      relatively small adverse impact on investment decisions by drug companies and
      venture capital firms, compared with the former.

PMID- 16966728
TI  - Specialty drug management.

PMID- 16966729
TI  - Benefit design and specialty drug use.
AB  - In this paper we examine spending by privately insured patients with four
      conditions often treated with specialty drugs: cancer, kidney disease, rheumatoid
      arthritis, and multiple sclerosis. Despite having employer-sponsored health
      insurance, these patients face substantial risk for high out-of-pocket spending.
      In contrast to traditional pharmaceuticals, we find that specialty drug use is
      largely insensitive to cost sharing, with price elasticities ranging from 0.01 to
      0.21. Given the expense of many specialty drugs, care management should focus on
      making sure that patients who will most benefit receive them. Once such patients
      are identified, it makes little economic sense to limit coverage.

PMID- 16966730
TI  - Health plans' strategies for managing outpatient specialty pharmaceuticals.
AB  - Balancing increased spending for specialty pharmaceuticals while providing
      affordable and equitable coverage for consumers is a key issue for public and
      private payers. Health plans rely on an array of strategies, including both
      medical management and those used for more traditional pharmaceuticals. To
      explore specific management strategies for outpatient specialty pharmaceuticals,
      a survey was administered to thirty-eight Blue Cross and Blue Shield plans,
      focused on identifying core strategies. Prior authorization was the most commonly
      used strategy, implemented by 83.3 percent of respondents. Other frequently
      implemented management strategies included claims review (82.8 percent),
      formulary management (76.7 percent), and utilization review (70 percent).

PMID- 16966731
TI  - Kaiser Permanente's evaluation and management of biotech drugs: assessing,
      measuring, and affecting use.
AB  - Two decades into the age of high-cost biotechnology medications, health care
      organizations are challenged to provide safe, effective treatment while managing
      costs. In a market lacking generic biotech drugs, health care organizations have
      few opportunities to negotiate reduced pricing; other strategies must be devised
      to manage use. Kaiser Permanente leverages its integrated health care delivery
      system to deploy management tools for costly therapies: evidence analysis, usage
      measurements, and multidisciplinary planning. Evidence-based medicine and
      realization of value provided by new therapies will depend on data capture and
      outcomes measurement, tools that are crucial to Kaiser Permanente's management of
      biotechnologies and effective use of members' financial resources.

PMID- 16966732
TI  - Managing biotechnology in a network-model health plan: a U.S. private payer
      perspective.
AB  - Emerging biotechnology poses challenges to payers, including access, coverage,
      reimbursement, patient selection, and affordability. Premera Blue Cross, a
      private regional health plan, developed an integrated cross-functional approach
      to managing biologics, built around a robust formulary process that is fast,
      flexible, fair, and transparent to stakeholders. Results are monitored by cost
      and use reporting from merged pharmacy and medical claims. Utilization management
      and case management strategies will integrate with specialty pharmacy programs to
      improve outcomes and cost-effectiveness. Creative approaches to provider
      reimbursement can align providers' incentives with those of the plan. Redesign of
      member benefits can also encourage appropriate use of biotechnology.

PMID- 16966733
TI  - Prices and availability of biopharmaceuticals: an international comparison.
AB  - This paper presents new evidence on availability, use, and prices of
      biopharmaceuticals in five major European Union (EU) markets, Canada, Australia,
      Japan, and Mexico, relative to the United States. Our data set from IMS Health
      includes all product sales in 2005. Per capita spending on biopharmaceuticals was
      at least twice as high in the United States as in the other countries. This
      difference reflects primarily greater availability and use of new, relatively
      high-price molecules and formulations. Prices for identical formulations are not
      higher on average in the United States. The broader price indexes, which do not
      control formulation, are also not higher in the United States, after adjusting
      for income.

PMID- 16966734
TI  - Market access for biopharmaceuticals: new challenges.
AB  - Biotechnology firms face new challenges as biologics account for an increasing
      share of product approvals and pipelines and their high costs are under scrutiny
      by regulators, employers, and consumers. Although the first generation of
      biologics often targeted niche markets with little impact on payers' total costs,
      the current product wave addresses larger populations. To meet the needs of all
      stakeholders, manufacturers must adopt an evidence-based approach including three
      principles: demonstration of clinical and economic value, price evolution
      according to market conditions (from orphan diseases to large areas such as
      diabetes), and an early timetable integrating clinical and economic endpoints.

PMID- 16966735
TI  - How direct-to-consumer television advertising for osteoarthritis drugs affects
      physicians' prescribing behavior.
AB  - Concern about the potential pernicious effect of direct-to-consumer (DTC) drug
      advertising on physicians' prescribing patterns was heightened with the 2004
      withdrawal of Vioxx, a heavily advertised treatment for osteoarthritis. We
      examine how DTC advertising has affected physicians' prescribing behavior for
      osteoarthritis patients. We analyzed monthly clinical information on fifty-seven
      primary care practices during 2000-2002, matched to monthly brand-specific
      advertising data for local and network television. DTC advertising of Vioxx and
      Celebrex increased the number of osteoarthritis patients seen by physicians each
      month. DTC advertising of Vioxx increased the likelihood that patients received
      both Vioxx and Celebrex, but Celebrex ads only affected Vioxx use.

PMID- 16966736
TI  - Teleradiology: a case study of the economic and legal considerations in
      international trade in telemedicine.
AB  - Growth in the global market for telemedical services is being driven by
      economics. Two operational models are already recognizable. "Nighthawk" providers
      are virtually indistinguishable from their domestic counterparts with respect to
      medical malpractice liability and price for service. Indian providers, in
      contrast, offer deep price discounts on services, but jurisdictional loopholes
      are likely to allow these providers a method to avoid medical malpractice
      liability. Hospitals that outsource their radiology services need to be aware of
      these differences, because hiring Indian telemedical providers will likely result
      in a shift of medical malpractice liability from providers to hospitals.

PMID- 16966737
TI  - Medicare payment for selected adverse events: building the business case for
      investing in patient safety.
AB  - This study estimates that Medicare extra payments under the hospital prospective
      payment system (PPS) range from about $700 per case of decubitus ulcer to $9,000
      per case of postoperative sepsis in the five types of adverse events identifiable
      in Medicare claims. Medicare extra payment for the five types of events totals
      more than $300 million per year, accounting for 0.27 percent of annual Medicare
      hospital spending. But these extra payments cover less than a third of the extra
      costs incurred by hospitals in treating these adverse events. We conclude that
      both Medicare and hospitals gain financially by improving patient safety.

PMID- 16966738
TI  - Mediating medical malpractice lawsuits against hospitals: New York City's Pilot
      Project.
AB  - The New York City Health and Hospitals Corporation participated in a feasibility
      study to measure the participants' satisfaction with mediation of medical
      malpractice lawsuits. Twenty-nine cases were referred to the study, twenty-four
      agreed to mediation, and nineteen were mediated. Satisfaction data indicate that
      the plaintiffs and their attorneys and the defendant's attorney were satisfied
      with the process whether or not settlement was reached. The mean length of a
      mediation was 2.34 hours. Of the cases mediated, thirteen settled, with a median
      payment of 111,000 dollars. The defendant's and plaintiffs' attorneys estimated
      spending approximately one-tenth the amount of time preparing their case for
      mediation that they would have spent preparing for trial.

PMID- 16966739
TI  - Poked and prodded again and again.

PMID- 16966740
TI  - My mother, a professional patient.

PMID- 16966741
TI  - The impact of quality-reporting programs on hospital operations.
AB  - We used data from the 2005-06 Community Tracking Study site visits to examine the
      impact of quality reporting on hospitals' data collection and review processes,
      feedback and accountability mechanisms, quality improvement activities, and
      resource allocation. Individual hospitals participate in multiple, varied
      reporting programs with distinct effects on hospital operations. Reporting
      programs play complementary roles in encouraging quality improvement but are
      poorly coordinated and command sizable resources, in large part because of
      inadequate information technology. Policy should be directed at encouraging
      formal assessments of how individual and combinations of programs affect quality
      outcomes, and the development of adaptable information systems.

PMID- 16966742
TI  - An evaluation of Oregon's evidence-based Practitioner-Managed Prescription Drug
      Plan.
AB  - This paper describes Oregon's implementation of its publicly developed, evidence
      based, Practitioner-Managed Prescription Drug Plan (PMPDP). Oregon's PMPDP was
      initially self-enforced with a dispense as written (DAW) exception process,
      followed by an educational prior authorization (soft PA) method, and finally no
      active enforcement. Market-share trends indicate that the educational prior
      authorization process was most effective at increasing the use of preferred
      agents. Pharmacy costs decreased 9.1 percent and 17.7 percent after
      implementation of the DAW and soft PA policies, respectively. Data from
      nonenforced PMPDP classes showed no change; this suggests the need for effective
      methods to encourage PMPDP compliance.

PMID- 16966744
TI  - Using pharmacoepidemiology to inform drug coverage policy: initial lessons from a
      two-province collaborative.
AB  - Prescription drug plan managers seek "real-world" evidence regarding the safety
      and effectiveness of drugs and drug coverage policies. University-based
      pharmacoepidemiologists with access to administrative health data can help meet
      these information needs and, by collaborating with other health plans, exploit
      variations in plan policy. Canada, with its universal health insurance, public
      drug benefit plans, and population-based linked health care databases, is an
      ideal setting for such research. Here we describe our initial experience in
      collaborating with researchers and drug plan managers in British Columbia and
      Ontario.

PMID- 16966745
TI  - More on premiums and practice.

PMID- 16966746
TI  - Malpractice premiums: analytic flaws.

PMID- 16966748
TI  - Yes, yes, and moving on.

PMID- 16966749
TI  - Why Indian physicians emigrate.

PMID- 16966750
TI  - Medical tourism.

PMID- 16966753
TI  - Human salmonellosis in travellers is highly correlated to the prevalence of
      salmonella in laying hen flocks.

PMID- 16966754
TI  - Mumps outbreak affecting adolescents and young adults in Austria, 2006: update.

PMID- 16966756
TI  - Outbreak of invasive meningococcal disease among soldiers in Skwierzyna, Poland,
      March 2006.

PMID- 16966755
TI  - Outbreak of Salmonella Kedougou in Norway associated with salami, April-June
      2006.

PMID- 16966752
TI  - Guidelines on the management of ascites in cirrhosis.

PMID- 16966757
TI  - European investigation into recent norovirus outbreaks on cruise ships: update.

PMID- 16966759
TI  - Outbreak of legionnaires disease in Amsterdam, June-July 2006.

PMID- 16966760
TI  - National outbreak of Salmonella Ajiobo infection in England and Wales, June 2006.

PMID- 16966761
TI  - US study finds that consistent condom use protects against genital human
      papillomavirus infection.

PMID- 16966762
TI  - Outbreak of legionnaires disease in Amsterdam, June-July 2006: source confirmed.

PMID- 16966763
TI  - Increase in cases of Crimean-Congo haemorrhagic fever, Turkey, 2006.

PMID- 16966764
TI  - Botulism associated with vacuum-packed smoked whitefish in Finland, June-July
      2006.

PMID- 16966765
TI  - Twenty years of active paediatric surveillance in the the UK and Republic of
      Ireland.

PMID- 16966766
TI  - Sexually acquired HIV infections on the rise in Catalonia, Spain.

PMID- 16966767
TI  - E-alert 24 July: Case of Lassa fever imported into Germany from Sierra Leone.

PMID- 16966768
TI  - Unexpected increase in case fatality of invasive group B streptococcal infections
      in infants in Norway, January-July 2006.

PMID- 16966769
TI  - Outbreak of measles in Belarus, January-June 2006.

PMID- 16966770
TI  - Avian influenza H5N1 update: resurgence in Thailand.

PMID- 16966771
TI  - Wound infections due to Vibrio cholerae in Sweden after swimming in the Baltic
      Sea, summer 2006.

PMID- 16966772
TI  - Heatwave in France, July 2006: 112 excess deaths so far attributed to the heat.

PMID- 16966773
TI  - Measles outbreak in Grosseto, central Italy, 2006.

PMID- 16966774
TI  - Tuberculosis and air travel: towards improved control.

PMID- 16966775
TI  - Emergence of EMRSA-15 clone in hospitals throughout the Czech Republic.

PMID- 16966776
TI  - Innovative new Swiss HIV prevention campaign: no action without protection.

PMID- 16966777
TI  - Resurgence of chikungunya virus in India: an emerging threat.

PMID- 16966778
TI  - Reducing salmonella in European egg-laying hens: EU targets now set.

PMID- 16966779
TI  - Diversity of needle exchange provision in the UK: findings from a national
      survey.

PMID- 16966780
TI  - Georgios Gouvras, head of DG SANCO's health threats unit.

PMID- 16966781
TI  - Vibrio vulnificus wound infections after contact with the Baltic Sea, Germany.

PMID- 16966782
TI  - Probable human anthrax death in Scotland.

PMID- 16966783
TI  - Outbreak of Salmonella Enteritidis infections in people attending a village event
      in Latvia.

PMID- 16966784
TI  - Removal of ticks: a review of the literature.

PMID- 16966785
TI  - Results from the integrated surveillance system for the 2006 Winter Olympic and
      Paralympic Games in Italy.

PMID- 16966787
TI  - Imported cases of chikungunya in metropolitan France: update to June 2006.

PMID- 16966788
TI  - Outbreak of Q fever in workers at a meat processing plant in Scotland, July 2006.

PMID- 16966789
TI  - Surveillance of enteric pathogens in Europe and beyond: Enter-net annual report
      for 2004.

PMID- 16966790
TI  - Typing of Legionella isolates during an epidemiological investigation can be
      helpful but also misleading: an example from Greece.

PMID- 16966793
TI  - Outbreak of extended spectrum beta-lactamase producing E. coli in a nursing home
      in Ireland, May 2006.

PMID- 16966794
TI  - Reducing the risks of transmitting gastrointestinal infections in home paddling
      pools.

PMID- 16966795
TI  - Healthcare associated infections in university hospitals in Latvia, Lithuania and
      Sweden: a simple protocol for quality assessment.
AB  - Surveillance of healthcare associated infections is an overlooked parameter of
      good clinical practice in most healthcare institutions, due to the workload
      demanded in the absence of adequate IT-systems. The aim of the present study was
      to investigate whether a simple protocol could be used to estimate the burden of
      healthcare associated infections in three university hospitals in Huddinge in
      Sweden, Riga in Latvia and Vilnius in Lithuania and form the basis for initiating
      a long term follow up system. The medical records of all patients receiving
      antibiotics were reviewed according to a standardised protocol, focusing on the
      indications for the drugs and on the frequency of hospital acquired infection
      (HAI) in a point-prevalence survey. Only comparable specialties were included.
      The proportion of patients treated with antibiotics (prophylaxis not included)
      were 63/280 (22%) in Huddinge, 73/649 (11%) in Riga and 99/682 (15%) in Vilnius.
      The proportion of admitted patients treated for a HAI were 15%, 3% and 4%,
      respectively, (both comparisons Huddinge versus other centres P <0.001). Surgical
      site infections were most common, followed by infections with an onset more than
      2 days after admission without any of the other registered risk factors present.
      Our inexpensive and simple method showed that healthcare associated infections
      were a significant problem among patients admitted to Huddinge. The figures
      obtained can be used for further discussion and form a baseline for follow up at
      the local level. The comparison of figures between centres was far less relevant
      than the process the study created.

PMID- 16966796
TI  - Antibiotic resistance in the southeastern Mediterranean--preliminary results from
      the ARMed project.
AB  - Sporadic reports from centres in the south and east of the Mediterranean have
      suggested that the prevalence of antibiotic resistance in this region appears to
      be considerable, yet pan-regional studies using comparable methodology have been
      lacking in the past. Susceptibility test results from invasive isolates of
      Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Enterococcus
      faecium and faecalis routinely recovered from clinical samples of blood and
      cerebrospinal fluid within participating laboratories situated in Algeria,
      Cyprus, Egypt, Jordan, Lebanon, Malta, Morocco, Tunisia and Turkey were collected
      as part of the ARMed project. Preliminary data from the first two years of the
      project showed the prevalence of penicillin non-susceptibility in S. pneumoniae
      to range from 0% (Malta) to 36% (Algeria) [median: 29%] whilst methicillin
      resistance in Staphylococcus aureus varied from 10% in Lebanon to 65% in Jordan
      [median: 43%]. Significant country specific resistance in E. coli was also seen,
      with 72% of isolates from Egyptian hospitals reported to be resistant to third
      generation cephalosporins and 40% non-susceptible to fluoroquinolones in Turkey.
      Vancomycin non-susceptibility was only reported in 0.9% of E. faecalis isolates
      from Turkey and in 3.8% of E. faecium isolates from Cyprus. The preliminary
      results from the ARMed project appear to support previous sporadic reports
      suggesting high antibiotic resistance in the Mediterranean region. They suggest
      that this is particularly the case in the eastern Mediterranean region where
      resistance in S. aureus and E. coli seems to be higher than that reported in the
      other countries of the Mediterranean.

PMID- 16966797
TI  - Diagnosis of non-viral sexually transmitted infections in Lithuania and
      international recommendations.
AB  - The aim of this study is to evaluate the range, quality and availability of
      diagnostic services for non-viral sexually transmitted infections (STIs), i.e. C.
      trachomatis, N. gonorrhoeae, T. vaginalis and T. pallidum, in Lithuania from
      September 2002 to December 2003. Surveillance data describing the organisation
      and performance characteristics of non-viral STI diagnostic services in Lithuania
      were collected using a questionnaire and subsequent site-visits. International
      evidence-based recommendations for non-viral STI diagnosis were used to evaluate
      the quality of the STI diagnostics. There were 171 facilities providing non-viral
      STI diagnostic services for the 3.5 million inhabitants of Lithuania. However,
      only 6% (n=9) of the respondents (n=153) could provide a confirmatory diagnosis,
      in accordance with international recommendations, for the full minimum range of
      relevant non-viral STIs in Lithuania, i.e. C. trachomatis, N. gonorrhoeae, T.
      pallidum, and T. vaginalis. In addition, accessibility to STI diagnostic services
      differed significantly among the different counties in Lithuania. Several of the
      respondents analysed low numbers of samples each year, and overall the sampling
      size was extremely low, especially for C. trachomatis diagnostics. In Lithuania,
      optimisation of non-viral STI diagnostics as well as of epidemiological
      surveillance and management of STIs is crucial. It may be worth considering a
      decrease in the number of laboratories, with those remaining having the
      possibility of performing STI diagnostic services that are optimised, in
      concordance with international recommendations, standardised, and quality assured
      using systematic internal and external quality controls and systems. In addition,
      establishment of national inter-laboratory networks and reference centres for non
      viral STIs is recommended.

PMID- 16966798
TI  - Epidemic conjunctivitis in Germany, 2004.
AB  - Epidemic conjunctivitis can be associated with viral or bacterial pathogens,
      whereas epidemic keratoconjunctivitis is caused mainly by adenoviruses type 8,19
      and 37. In Germany, the incidence of adenovirus conjunctivitis cases increased
      from 0.2 per 100,000 inhabitants (in 2001 and 2002) eventually to 0.5 in 2003 and
      0.8 in 2004. The detection of adenovirus in conjunctival swabs is notifiable to
      the local health departments. Data about cases with positive conjunctival swabs
      are then transmitted to the Robert Koch-Institut. Quality control of data takes
      place and national surveillance data of confirmed cases with adenovirus
      conjunctivitis are published. From January to April 2004 the national
      surveillance system captured an outbreak with 1024 cases (131 laboratory
      confirmed). Analysis of the national surveillance data showed that in March 2004
      the group primarily affected by epidemic keratoconjunctivitis was young men
      between 18-29 years old followed by an increased number of notifications from
      women in the same age group. Meanwhile the German Armed Forces experienced an
      outbreak of conjunctivitis, almost exclusively without laboratory confirmation,
      affecting 6378 soldiers. Despite the small number of laboratory confirmed cases
      it became clear from the analysis of the national surveillance data that person
      to-person transmission between young men and similar age groups of the population
      did occur. Whether the outbreak started within the garrisons of the German Armed
      Forces or whether it was triggered within these accommodations, there is clearly
      a need for the national and the military public health institutions to work
      together on guidelines to handle future challenges.

PMID- 16966799
TI  - Shiga toxin-producing Escherichia coli (STEC) O157 outbreak, The Netherlands,
      September-October 2005.
AB  - In September 2005, the first national food-related outbreak of Shiga toxin (Stx)
      producing Escherichia coli (STEC) O157 was investigated in the Netherlands. A
      total of 21 laboratory-confirmed cases (including one secondary case), and
      another 11 probable cases (two primary and nine secondary cases) were reported in
      patients who became ill between 11 September and 10 October 2005. Preliminary
      investigation suggested consumption of a raw beef product, steak tartare (in the
      Netherlands also known as "filet americain"), and contact with other symptomatic
      persons as possible risk factors. A subsequent case-control study supported the
      hypothesis that steak tartare was the source of the outbreak (matched odds ratio
      (OR) 272, 95% confidence interval (CI) 3-23,211). Consumption of ready-to-eat
      vegetables was also associated with STEC O157 infection (matched OR 24, 95% CI
      1.1-528), but was considered a less likely source, as only 40% of the cases were
      exposed. Samples of steak tartare collected from one chain of supermarkets where
      it is likely that most patients (67%) bought steak tartare, all tested negative
      for STEC O157. However, sampling was done three days after the date of symptom
      onset of the last reported case. Since 88% of the cases became ill within a two
      week period, point source contamination may explain these negative results. It is
      concluded that steak tartare was the most likely cause of the first national food
      related outbreak of STEC O157 in the Netherlands.

PMID- 16966800
TI  - Prolonged outbreak of B meningococcal disease in the Seine-Maritime department,
      France, January 2003 to June 2005.
AB  - Between January 2003 and June 2005, an outbreak of meningococcal disease occurred
      in the department of Seine-Maritime in northern France. Eighty six cases were
      notified, giving an average annual incidence of 2.7 cases per 100,000
      inhabitants, compared with 1.6 in France. An especially affected area was defined
      as the city of Dieppe and its surrounding area (26 cases, giving an annual
      incidence of 12 cases per 100,000). This outbreak was due to N. meningitidis
      phenotype B:14:P1.7,16 belonging to the clonal complex ST-32/ET-5. Over the 31
      B14:P1.7,16 cases confirmed by phenotyping methods at the national reference
      centre for meningococci (CNR, Centre National de Reference des meningocoques) the
      case-fatality rate (19%) and the proportion of purpura fulminans (42%) were
      especially high. Teenagers aged between 15 and 19 years and children aged 1 to 9
      years were the most affected. In 2003, health authorities put in place enhanced
      epidemiological surveillance and informed practitioners and population about the
      disease. In 2004, the national vaccination advisory board studied the opportunity
      of using a non licensed outer membrane vesicle vaccine developed in Norway which
      may be effective against the B14:P1.7,16 strain. The Ministry of health decided
      in 2006 to offer vaccination with this vaccine to people aged 1 to 19 years in
      Seine-Maritime.

PMID- 16966801
TI  - Is there a need for a public vaccine production capacity at European level?

PMID- 16966802
TI  - Magnetic susceptibility measurements of solutions by surface nanodisplacement
      detection.
AB  - A new principle to measure the magnetic susceptibility of a solution was
      proposed; it utilized the displacement of solution surface caused by the magnetic
      force applied to the solution. The interfacial displacement was measured with the
      sensitivity of 5 nm from a change of the interference fringes, so called Newton
      Ring, generated from the solution surface and an upper surface of a small plano
      convex lens on the bottom wall of a cell. The surface displacement measurement
      was carried out in a homemade cell attached by one or two small Nd-Fe-B magnets.
      The performance of this method was investigated by the measurements of magnetic
      susceptibility of manganese(II) chloride solution and some lanthanide(III)
      solutions. An excellent linear relationship between the magnetic susceptibility
      and the interfacial displacement was observed for each solution system. Then, it
      was demonstrated that this relationship could be used for the determination of
      the magnetic susceptibility of solutions or the concentration of a solute by
      using the manganese(II) solution as a standard solution.

PMID- 16966803
TI  - On-line preconcentration system using mini-column packed with a chelating resin
      for the characterization of seasonal variations of trace elements in seawater by
      ICP-MS and ICP-AES.
AB  - An on-line column preconcentration technique coupled with inductively coupled
      plasma-mass spectrometry (ICP-MS) and -atomic emission spectrometry (ICP-AES) was
      developed using a mini-column (ca. 3 mm i.d., 40 mm length), that was packed with
      chelating resin (0.2 g) of iminodiacetic acid groups, Muromac A-1. After the
      preconcentration step, the column was washed with ammonium acetate buffer (pH
      5.5) and water to remove major elements, such as Ca and Mg, and then eluted with
      4 ml of 2 mol l(-1) nitric acid. Eleven trace elements (Al, V, Fe, Co, Ni, Cu,
      Zn, Cd, Pb, Th and U) in seawater were determined by ICP-MS/AES. Recoveries for
      most of the elements tested were over 90%, although those for Al, V and Th were
      around 70%. The accuracy of the proposed method was evaluated by analyzing a
      standard reference material of seawater (NASS-4, NRC Canada). The values of Fe,
      Co, Ni, Cu, Zn, Cd and Pb obtained with the present method showed good agreement
      with the certified values as judged from the standard deviation. The method was
      successfully applied to characterize seasonal variations of trace elements in
      deep seawater (DSW) and surface seawater (SSW). In addition, no serious decrease
      in analytical performance of the present column system was observed during the
      experimental period of about 1 year.

PMID- 16966804
TI  - Solvent sublation and spectrometric determination of iron(II) and total iron
      using 3-(2-pyridyl)-5,6-bis(4-phenylsulfonic acid)-1,2,4-triazine and
      tetrabutylammonium bromide.
AB  - Solvent sublation has been studied for the separation and determination of trace
      iron(II) in various kinds of water samples. A strongly magenta-colored anionic
      [Fe(FZ)3](4-) complex was formed at pH 5.0 upon adding 3-(2-pyridyl)-5,6-bis(4
      phenylsulfonic acid)-1,2,4-triazine (ferrozine, FZ) to the sample solution.
      Tetrabutylammonium bromide (TBAB) was added in the solution to form the
      (TBA)4[Fe(FZ)3)] ion pair, and an oleic acid (HOL) surfactant was added. Then,
      the (TBA)4[Fe(FZ)3] ion pairs were floated by vigorous shaking in the flotation
      cell and extracted into methyl isobutyl ketone (MIBK) on the surface of the
      aqueous solution. The iron collected in the MIBK layer was measured directly by
      spectrophotometry and/or flame atomic-absorption spectrophotometry. Different
      experimental variables that may affect the sublation efficiency were thoroughly
      investigated. The molar absorptivity of the (TBA)4[Fe(FZ)3] ion pair was 2.8 x
      10(4) l mol(-1) cm(-1) in the aqueous layer. Beer's law held up to 1.0 mg L(-1)
      Fe(II) in the aqueous as well as in the organic layers. The adopted solvent
      sublation method was successfully applied for the determination of Fe(II) in
      natural water samples with a preconcentration factor of 200. The application was
      extended to determine iron in pharmaceutical samples.

PMID- 16966805
TI  - Onboard determination of submicromolar nitrate in seawater by anion-exchange
      chromatography with lithium chloride eluent.
AB  - Ion-exchange chromatography using a high-capacity anion exchanger with UV
      detection was applied to the determination of nitrate in seawater. Major ions in
      seawater samples did not affect the peak shape and the retention time of the
      nitrate when an alkaline metal cation-chloride solution was used as an eluent at
      high concentrations (0.5-2 mol/l). At a wavelength of 220 nm, the peak of bromide
      was very small because of low absorption, while its separation from the nitrate
      peak was good at high concentrations. Among the eluents tested, lithium chloride
      gave the best separation of nitrate from bromide. It was estimated that the
      lithium ion had the least potential for ion-pair formation with nitrate, and its
      retention time was prolonged compared with the retention times when using other
      cations; with bromide and nitrite, such an effect was not observed. The results
      of shipboard seawater nitrate determination by our method in the South Pacific
      Ocean and Antarctic Sea showed good agreement with those by the conventional
      photometric method using continuous flow.

PMID- 16966806
TI  - Determination of Pb(II), Cu(II) and Fe(III) with capillary electrophoresis using
      ethylenediaminetetraacetic acid as a complexing agent and vancomycin as a complex
      selector.
AB  - The simultaneous determination of metal ions using ethylenediaminetetraacetic
      acid (EDTA) as a complexing agent and vancomycin as a complex selector was
      successfully studied by capillary electrophoresis with the U-shaped cell. The
      partial filling method (counter current mode) was used in order to gain
      selectivity of the separation, and also to increase the detection sensitivity.
      The effect of the vancomycin concentration on the separation behavior of free
      EDTA and metal products, and the effect of the EDTA concentration on the
      stability of metal-EDTA products were considered. Under the optimal condition,
      the reproducibilities (RSD) of the migration time and the peak area were less
      than 3.39% and 9.61%, respectively. With the high sensitivity of the method,
      Pb(II), Cu(II) and Fe(III) in tap water were successfully determined, and the
      recoveries were 99 - 105%. The concentrations of these metal ions found in tap
      water did not exceed the maximum allowed concentrations regulated by the U.S.
      Environmental Protection Agency.

PMID- 16966807
TI  - Weak interaction between inhibition peptides and a soluble receptor of fusion
      protein in the liquid phase.
AB  - Fluorescence polarization analysis (FPA) of a liquid-phase method was carried out
      with a glycosylphosphatidylinositol (GPI) anchored membrane receptor bone marrow
      stromal cell antigen 1 (BST-1, CD157) as a model receptor for medical screening.
      A soluble receptor, BST1-Fc, was prepared by fusing the extracellular domain of
      BST-1 and the Fc region of human immunoglobulin G (IgG). The binding curves of
      BST1-Fc with a fluorescently labeled ligand peptide, or its three derivatives,
      were developed using ordinary FPA in the liquid phase. The obtained dissociation
      constants (Kd) were comparable with those reported as measured with SPR of a
      solid-phase method, except for one derivative peptide with Kd larger than 7000
      nM. Competitive FPA was carried out, and it was demonstrated that a very weak
      interaction, which would be difficult to detect with SPR or other solid-phase
      methods, could be analyzed with both ordinary and competitive FPA.

PMID- 16966808
TI  - Determination of daunomycin in human plasma and urine by using an interference
      free analysis of excitation-emission matrix fluorescence data with second-order
      calibration.
AB  - Daunorubicin (DNR) is a significant antineoplastic antibiotic, which is usually
      applied to a chemotherapy of acute lymphatic and myelogenous leukaemia.
      Unfortunately, cardiotoxicity research in animals has indicated that DNR is
      cardiotoxic. Therefore, it is important to quantify DNR in biological fluids. A
      new algorithm, the alternating fitting residue (AFR) method, and the traditional
      parallel factor analysis (PARAFAC) have been utilized to directly determine DNR
      in human plasma and urine. These methodologies fully exploit the second-order
      advantage of the employed three-way fluorescence data, allowing the analyte
      concentrations to be quantified even in the presence of unknown fluorescent
      interferents. Furthermore, in contrast to PARAFAC, more satisfactory results were
      gained with AFR.

PMID- 16966809
TI  - Evaluation of powdered infant formula milk as chelating agent for copper under
      simulated gastric conditions of a baby's stomach.
AB  - The objective of this study was to determine the complexing capacity of four
      types of powdered commercial milks with copper(II) using square wave adsorptive
      stripping voltammetry. Two were types of cow milk adapted for babies under one
      year (A and B), one was soymilk (C) and the other was normal milk (D). Milk
      solutions were prepared following the instructions shown on the milk container,
      and they were mixed with a pepsin solution simulating a baby's stomach conditions
      (pepsin and salts concentration, pH and temperature). Complexing capacity was
      determined by titrating milk samples with aliquots of a standard copper solution
      until the peak current due to solvated or free copper ions was increasing.
      Assuming a 1:1 copper-milk complex, the apparent stability constant was found
      using the pseudopolarogram method. The log K'(Cu-milk) values were 4.9, 5.0, 3.0
      and 5.1 for A, B, C and D types of milk, respectively. Voltammograms of the milk
      solution as a function of copper added show that the binding properties of the
      four types of powdered milk studied were different and that saturation of the
      four types, occurs at different copper concentrations. Concentrations obtained
      were: 4.9, 5.8, 1.1 and 10.1 mM for A, B, C and D types, respectively. The best
      complexing agent was the solution prepared with powdered milk D and the worst was
      that of C. This is important for the bioavailability of this element as a
      micronutrient.

PMID- 16966810
TI  - Application of crude extract of kohlrabi (Brassica oleracea gongylodes) as a rich
      source of peroxidase in the spectrofluorometric determination of hydrogen
      peroxide in honey samples.
AB  - Crude extract of kohlrabi (Brassica oleracea gongylodes) was prepared by a simple
      procedure and its enzymatic activity and total protein concentration were
      determined. It was found that this crude extract is a rich source of peroxidase
      (POx) and has high specific activity. Cross-linked polyvinylpyrrolidone was used
      as a stabilizer in the preparation of the crude extract. The POx activity of
      kohlrabi crude extract did not vary for at least 2 months when deoxygenated and
      stored at 4 degrees C. This extract was applied for the spectrofluorometric
      determination of hydrogen peroxide using homovanillic acid as a fluorogenic
      substrate. POx catalyzes the hydrogen peroxide oxidation of homovanillic acid to
      produce a dimer which shows strong fluorescence at 420 nm with excitation at 312
      nm. In the optimum conditions, the calibration graph for hydrogen peroxide was
      linear up to 190 ng mL(-1), with a detection limit of 4.4 ng mL(-1). The relative
      standard deviation (RSD) was 1.48% for 50 ng mL(-1) hydrogen peroxide. The
      proposed method was successfully applied to the determination of hydrogen
      peroxide in honey. The concentration-time profile of H2O2 produced upon dilution
      of honey was studied and H2O2 contents of some different honeys from various
      areas of Iran were determined.

PMID- 16966811
TI  - Amperometric immunosensor for the detection of Vibrio cholerae O1 using
      disposable screen-printed electrodes.
AB  - A disposable amperometric immunosensor was studied for the rapid detection of
      Vibrio cholerae (V. cholerae), the causative agent of cholera, employing an
      indirect sandwich enzyme linked immunosorbent assay (ELISA) principle. Screen
      printed electrodes (SPEs) were fabricated (by using commercial and homemade
      carbon inks), electrochemically characterized and the assay conditions were
      optimized for capturing antibodies and antigen. Whole cell lysate (WCL) of V.
      cholerae was used to raise antibodies in rabbits and mice. The antibodies raised
      against WCL of V. cholerae were found to be specific, and no cross reactivity was
      observed with other enteric bacteria. 1-Naphthyl phosphate was used as a
      substrate with the amperometric detection of its enzymatic hydrolysis product 1
      naphthol at a potential of +400 mV vs. Ag/AgCl reference electrode. A comparison
      between the amperometric detection technique and the standard ELISA was made in
      terms of the total assay time, the amount of biological materials used and the
      sensitivity of detection. The minimum detection limit of the amperometric
      immunosensor for V. cholerae was found to be 10(5) cells/ml in 55 min, while
      ELISA detected 10(6) cells/ml in 4 h.

PMID- 16966812
TI  - Electrocatalytic oxidation and highly selective voltammetric determination of L
      cysteine at the surface of a 1-[4-(ferrocenyl ethynyl)phenyl]-1-ethanone modified
      carbon paste electrode.
AB  - A carbon paste electrode (CPE) chemically modified with 1-[4-(ferrocenyl
      ethynyl)phenyl]-1-ethanone (4-FEPEMCPE) was employed to study the
      electrocatalytic oxidation of L-cysteine using cyclic voltammetry, differential
      pulse voltammetry and double potential step chronoamperometry as diagnostic
      techniques. The diffusion coefficient (D = 7.863 x 10(-6) cm2 s(-1)) of L
      cysteine was also estimated using chronoamperometry. The electron-transfer
      coefficient, alpha (= 0.40), for L-cysteine at the surface of 4-FEPEMCPE was
      determined using cyclic voltammetry technique. It was found that under an optimum
      pH (= 7.00), the oxidation of L-cysteine at the surface of such an electrode
      occurred at a potential of about 350 mV less positive than that of an unmodified
      CPE. The catalytic oxidation peak currents represented a linear dependence on the
      L-cysteine concentration. Linear analytical curves were obtained in the ranges of
      9.0 x 10(-5) - 4.9 x 10(-3) M and 2.0 x 10(-5) - 2.8 x 10(-3) M of L-cysteine
      with correlation coefficients of 0.9981 and 0.9982 in cyclic voltammetry and
      differential pulse voltammetry, respectively. The detection limits (2 sigma) were
      determined to be 9.9 x 10(-6) M and 5 x 10(-6) M with cyclic voltammetry and
      differential pulse voltammetry, respectively. The influences of twenty other
      amino acids, such as glutamine, L-glutamic acid, L-glysine, L-histidine, L
      isoleucine, L-leucine, L-arginine hydrochloride, L-aspargine, L-aspartic acid, S
      carboxy methyl-L-cysteine, L-methionine, L-phenyl alanine, L-proline, L-serine, L
      threonine, L-cystine, cysteamine and gluthathione, on the current response of the
      sensor were examined. The obtained results did not show any influence on the
      analytical signal of L-cysteine by these amino acids (except for cysteamine). The
      method was also used for the selective determination of L-cysteine in patient
      blood plasma and some pharmaceutical preparations by using standard addition
      method.

PMID- 16966813
TI  - Thiocyanate ion-selective PVC membrane electrode based on N,N'-ethylene-bis(4
      methylsalicylidineiminato)nickel(II).
AB  - A highly selective poly(vinyl chloride) (PVC) membrane electrode based on an N,N'
      ethylene-bis(4-methyl-salicylidineiminato) nickel(II) [Ni(EBMSI)] complex as a
      carrier for a thiocyanate-selective electrode is reported. The influences of the
      membrane composition, pH and possible interfering anions were investigated based
      on the response properties of the electrode. The electrode exhibited a good
      Nernstian slope of -58.9 +/- 0.7 mV decade(-1), over a wide pH range of 3.5 - 8.5
      and a linear range of 1.0 x 10(-6) - 1.0 x 10(-1) M for thiocyanate. The
      detection limit of electrode was 3.1 x 10(-7) M SCN(-). The selectivity
      coefficients determined by a fixed interference method (FIM) indicate that a good
      discriminating ability towards the SCN- ion compared to other anions. The
      proposed sensor had a fast response time of about 5 - 15 s and could be used for
      at least 3 months without any considerable divergence in the potential. It was
      applied as an indicator electrode in the titration of thiocyanate with Ag+ and in
      the potentiometric determination of thiocyanate in saliva and urine samples.

PMID- 16966814
TI  - An improved colorimetric determination of lead(II) in the presence of nonionic
      surfactant.
AB  - Phenanthraquinone monophenyl thiosemicarbazone (PPT), an excellent color-forming
      chelating agent, combines to Pb(II) to form a slightly soluble complex in aqueous
      solution. To determine this metal ion, a tedious and time-consuming separation
      technique, such as liquid-liquid extraction, has to be performed. However, the
      Pb(II)-PPT complex could be determined conveniently by ultraviolet-visible (UV
      Vis) spectrophotometry at 520 nm in a Tween 80 micellar medium that has
      polyoxyethylene groups. After conditions, such as the pH, the concentration of
      PPT and the stability, were adjusted to their optimum values, the sensitivities
      of the Pb(II) ions in the Tween 80 micellar medium and in chloroform were
      compared. It was shown that the sensitivity of Pb(II) in the Tween 80 micellar
      medium was higher than in chloroform. The interference from different cations and
      anions was studied. Beer's law was obeyed over a concentration range of 0-40
      microg ml(-1). The detection limit of Pb(II) was 0.036 microg ml(-1). The
      recovery yields of the lead(II) in the synthetic mixtures and water samples
      ranged from 98 to 99.8%, and their relative standard deviations (RSD) were below
      4%. The proposed method was successfully applied to the determination of lead in
      certified reference samples, biological samples and in environmental water
      samples.

PMID- 16966815
TI  - Sequential injection analysis for Cr(VI) and Cr(III) with renewable surface
      reflection spectrophotometry.
AB  - On the basis of the chromogenic reaction of chromium(VI) with 1,5
      diphenylcarbohydrazide (DPC) on the surface of Polysorb C-18 beads and the
      sequential injection renewable surface technique (SI-RST), a highly sensitive
      reflect spectrophotometric method for the determination of chromium(III) and
      chromium(VI) was proposed. Considerations of system and flow cell design, and
      factors that influence the determination performance were discussed. With 300
      microl of sample loaded and 0.6 mg of beads trapped, the linear response range
      was 0.02 - 0.5 mg l(-1) Cr(VI) with a detection limit (3 sigma) of 2.4 microg l(
      1) Cr(VI). The method achieves a precision of 1.3% RSD (n = 11) and a throughput
      of 53 samples per hour. The determination of Cr(III) was based on the same
      reaction for the determination of Cr(VI) after being oxidized by (NH4)2S2O8. The
      precision of the oxidation method was evaluated using a 0.2 mg l(-1) Cr(III)
      standard, yielding an RSD of 2.5% (n = 11). The average recovery of Cr(III)
      oxidized was tested to be 99.1%. The proposed method was used in the simultaneous
      determination of Cr(VI) and Cr(III) in water samples, and the error was less than
      3%.

PMID- 16966816
TI  - Control of the bioluminescence starting time by inoculated cell density.
AB  - In this study, we attempted to control the timing of light-emission from
      bioluminescent bacteria, by changed cell numbers inoculated into medium. Luminous
      bacteria express bioluminescence when the number of cells reached a threshold.
      Inoculated cell density had an effect on the time of bioluminescence starting.
      Samples were prepared by varying cell density of inoculation. In the results, all
      the vials showed different luminescence profiles in the order of inoculated cell
      population.

PMID- 16966817
TI  - Chitosan as cationic polyelectrolyte for the modification of electroosmotic flow
      and its utilization for the separation of inorganic anions by capillary zone
      electrophoresis.
AB  - Cationic polyelectrolyte of chitosan was used for the reversal of electroosmotic
      flow in capillary zone electrophoresis. The chitosan was dissolved in acetic acid
      solution, and stable electroosmotic flow was obtained at the chitosan
      concentrations between 50 and 300 microg/mL. Separation of inorganic anions was
      carried out using the dynamically coated capillary by capillary zone
      electrophoresis. Nine kinds of anions were separated and detected with the
      capillary. The electrophoretic mobility of the analyte anions decreased with
      increasing concentrations of chitosan in the migrating solution through ion-ion
      interaction, but the migration order of the analyte anions was not changed in the
      concentration range of the chitosan examined. The signal shape for the analyte
      anions was developed by using field-enhanced sample stacking with 10 mM sodium
      sulfate.

PMID- 16966818
TI  - Synthesis and application of amberlite XAD-2 functionalized with dithizone for
      field preconcentration and separation of trace cadmium in seawater.
AB  - A chelating resin coupling Amberlite XAD-2 functionalized with dithizone is
      synthesized and characterized. Dissolved cadmium is field-preconcentrated using a
      minicolumn packed with the synthesized resin and determined by flame atomic
      absorption spectrometry. Five experimental variables are evaluated. The
      enrichment factor of 416 is obtained for 50 mL of sampling volume, and the
      detection limit (3 sigma) of the procedure is 6.7 ng L(-1). The precision (RSD)
      for 11 independent determinations is 1.97%. This method has been successfully
      applied to the determination of cadmium in natural seawater samples.

PMID- 16966819
TI  - Rapid study of fragrance loss from commercial soap after use by solid phase
      microextraction-GC/MS and olfactory evaluation.
AB  - A quick and reliable approach was reported to measure the perfume loss in a
      commercial soap sample after continued use. This work firstly studied the
      fragrance loss profile in soap scientifically combined and compared with
      traditional olfactory evaluation. Solid-phase microextraction (SPME), as a simple
      and effective adsorption and desorption technique, was selected here to eliminate
      the needs of organic solvents or complicated apparatus; more importantly, SPME
      kept the soap intact and made it available for continued study. Thanks to control
      of the sampling time and other extraction parameters, a consistent and reliable
      result was achieved, which was much better and more detailed than traditional
      olfactory evaluation done by human beings.

PMID- 16966820
TI  - Analysis of ethanol and methanol in human body fluids by headspace solid phase
      microextraction coupled with capillary gas chromatography.
AB  - A new method for extraction and analysis of ethanol and methanol in human whole
      blood, urine and saliva samples based on headspace solid phase microextraction
      (SPME) using silver sulfide (Ag(2)S) and polyvinyl chloride (PVC) coated on
      silver wire is described. Unlike commercial fibers, which are coated on fused
      silica, the proposed fiber has a metallic base to which the coating adheres very
      strongly. Due to metallic base, this fiber is very durable and is thermally
      stable up to 250 degrees C. After optimization of coating composition and
      microextraction conditions, the fiber was used for sampling of methanol and
      ethanol from human body fluids prior to capillary gas chromatographic analysis.
      The high recovery (>94%), low detection limits (5.6 mg/L for ethanol and 12.8
      mg/L for methanol) and excellent linearity (>0.9900) of calibration graphs made
      the proposed method suitable for this purpose.

PMID- 16966821
TI  - Liquid-chromatographic separation and determination of process-related
      impurities, including a regio-specific isomer of celecoxib on reversed-phase C18
      column dynamically coated with hexamethyldisilazane.
AB  - A simple and rapid reversed-phase high-performance liquid-chromatographic method
      for the separation and determination of process-related impurities of celecoxib
      (CXB) in bulk drugs and pharmaceuticals was developed. The separation of
      impurities viz., 4-methylacetophenone (I), 1-(4-methylphenyl)-4,4,4
      trifluorobutane-1,3-dione (II), 4-hydrazinobenzene sulfonamide (III) and a regio
      specific isomer [3-(4-methylphenyl)-5-trifluoromethyl-1H-pyrazole-1-yl]
      benzenesulfonamide (IV), was accomplished on an Inertsil ODS-3 column dynamically
      coated with 0.1% hexamethyldisilazane (HMDS) in acetonitrile:water (55:45 v/v) as
      a mobile phase and detection at 242 nm using PDA at ambient temperature. The
      chromatographic conditions were optimized by studying the effects of HMDS, an
      organic modifier, time of silanization and column temperature. The method was
      validated and found to be suitable not only for monitoring the synthetic
      reactions, but also to evaluate the quality of CXB.

PMID- 16966822
TI  - Application of the nanogold-4,4'-bis(methanethiol)biphenyl modified gold
      electrode to the determination of tyrosinase-catechol reaction kinetics in
      acetonitrile.
AB  - The reactivity of tyrosinase adsorbed on nanogold bound with 4,4'
      bis(methanethiol)biphenyl monolayer self-assembled on a gold disk with catechol
      in a dipolar aprotic solvent, acetonitrile (AN), was studied by cyclic
      voltammetric and amperometric methods. Tyrosinase exhibited characteristics of a
      Michaelis-Menten kinetic mechanism. The tyrosinase attached to the nanogold
      continued to react with substrates in AN even when the water content was lower
      than 0.01 w/w%. The apparent Michaelis-Menten constant K(m) of tyrosinase for
      catechol is 5.5 +/- 0.4 mM (n = 5).

PMID- 16966823
TI  - Preparation and certification of the new reference materials; plastics (disk
      form, JSAC 0621-0625) for determination of mercury using x-ray fluorescent
      analysis.
AB  - The Japan Society for Analytical Chemistry has developed some new plastic
      certified reference materials (CRMs) for the analysis of mercury in polyester
      disks using XRF analysis. These CRMs (named as JSAC 0621-0625) were prepared by
      casting polyesters including a toluene solution of organometallic compounds as a
      standard. Concentrations of the five levels of mercury ranged from 0 to 250
      mg/kg. Homogeneity tests of prepared disks had shown excellent results.
      Interlaboratory comparison study for the certification was performed by 15
      laboratory participants. The z-scores in robust statistical method was applied
      for the evaluation of outliers. The certified values were assigned after
      discarding outliers. The uncertainties of certified values were determined as the
      confidence levels of 95%.

PMID- 16966825
TI  - Postprandial reactive hypoglycemia in an oldest-old patient effectively treated
      with low-dose acarbose.
AB  - We recently encountered a 96-year-old Japanese woman who suffered from frequent
      hypoglycemia. Endocrinological and imaging data eliminated the possibility of
      insulinoma, whereas oral glucose tolerance testing revealed impaired glucose
      tolerance and subsequent reactive hypoglycemia. The patterns between insulin or C
      peptide secretions and glucose excursions demonstrated that the discrepancy
      occurred in the late postprandial stage. Administration of small doses of alpha
      glucosidase inhibitor (alpha-GI) dramatically inhibited the rapid rise and
      subsequent precipitous fall of plasma glucose. Reactive hypoglycemia may be one
      of the important cause of hypoglycemia in the elderly, and alpha-GI could
      effectively and safely prevent such hypoglycemic attacks in those patients.

PMID- 16966826
TI  - Loss of consciousness and hypokalemia in an elderly man with a mutation of the
      thiazide-sensitive Na-Cl cotransporter gene.
AB  - An 80-year-old man was referred to our department for evaluation of repetitive
      loss of consciousness and faintness with hypokalemia. He had relatively low blood
      pressure, hypomagnesemia, hypocalciuria and chondrocalcinosis in the knee,
      clinically suggesting Gitelman's syndrome. A renal clearance study could not be
      carried out due to the patient's age and complications of the heart. Sequence
      analysis of the gene of thiazide-sensitive Na-Cl cotransporter (TSC) showed a
      heterozygous missense mutation from C to T at 1712 base pairs from the
      translation start site, with resultant changes in codon 569 from alanine to
      valine (A569V). Treatment with oral administration of potassium chloride improved
      all the symptoms. Although Gitelman's syndrome has been considered to be
      autosomal recessive, cases of only heterozygous mutation detected have recently
      been reported. Therefore, the mutation found in this patient may be responsible
      for Gitelman's syndrome.

PMID- 16966827
TI  - Serum hyaluronan concentration as a marker of angiopathy in patients with
      diabetes mellitus.
AB  - Accumulation of hyaluronan (HA) around smooth muscle cells in lesions of
      atherosclerosis in diabetic patients suggests that this protein plays an
      important role in diabetic angiopathy. The aim of this study was to determine the
      correlation between serum HA concentrations and diabetic angiopathy. Diabetic
      patients treated with or without an oral hypoglycemic agent and/or insulin for at
      least 1 year were recruited (n = 95). We also included 20 non-diabetic control
      subjects. We measured serum levels of HA, body mass index (BMI), fasting plasma
      glucose (FPG), HbA1c, total cholesterol, triglyceride, glycated albumin (GA),
      high sensitivity CRP (hs-CRP), monocyte chemoattractant protein (MCP)-1 and
      evaluated diabetes mellitus history, drug use and presence of related
      complications. Serum HA levels were significantly (P<0.05) higher in diabetic
      patients (83.6 +/- 5.6 ng/ml, mean +/- SEM) than in normal subjects (41.7 +/- 12
      ng/ml). In diabetic patients, serum HA concentration significantly correlated
      with FPG, HbA1c, GA, triglyceride and also significantly correlated with BMI, hs
      CRP and MCP-1 and tended to be higher in diabetic patients with complications
      than in those without such complications. Our data suggest that serum HA level
      correlates with poor blood glucose control and diabetic angiopathy and that it
      could be used as a marker of diabetic angiopathy.

PMID- 16966828
TI  - Interleukin-12B gene polymorphism does not confer susceptibility to Graves'
      ophthalmopathy in Japanese population.
AB  - Graves' disease (GD) is an autoimmune disorder with genetic predisposition and
      frequently associated with Graves' ophthalmopathy (GO). Interleukin 12 (IL-12) is
      an important mediator of inflammatory immune responses and is expressed in the
      thyroid and orbit. IL-12B gene, which encodes the p40 subunit of IL-12, is
      located at chromosome 5q31-33. The aim of the present study was to investigate
      whether IL-12B gene polymorphism is associated with the development of GD or GO.
      IL-12B gene polymorphism was studied in Japanese GD patients (n = 329) and
      healthy control subjects without anti-thyroid autoantibodies or a family history
      of autoimmune disorders (n = 226). The A/C polymorphism at position 1188 of the
      3' untranslated region (3'UTR) of the IL-12B gene was analyzed using the
      polymerase chain reaction--restriction fragment length polymorphism method. There
      was no difference in allele or genotype frequency of the IL-12B gene polymorphism
      (1188A/C) between GD patients and control subjects. There was no association of
      the IL-12B gene polymorphism with ophthalmopathy, severity of hyperthyroidism or
      serum IgE levels. There was no association of the IL-12B gene polymorphism with
      serum IL-12 levels, which were significantly elevated in hyperthyroid phase of
      GD. In conclusion, IL-12B gene 1188A/C polymorphism is not associated with GD or
      GO susceptibility in Japanese.

PMID- 16966829
TI  - Possible relationship between adiponectin and renal tubular injury in diabetic
      nephropathy.
AB  - Adiponectin is an adipose-derived protein which has anti-inflammatory and anti
      atherogenic properties in addition to insulin-sensitizing effects. To date, the
      role of adiponectin in the pathogenesis of diabetic nephropathy remains unclear.
      The aim of the present study was to explore the relationship between adiponectin
      and renal tubular injury in diabetic nephropathy. We determined serum and urinary
      adiponectin levels in type 2 diabetic patients with normoalbuminuria (n = 19),
      microalbuminuria (n = 18), and overt diabetic nephropathy (n = 16), and then
      analyzed the correlations between serum and urinary adiponectin, urinary N
      acetylglucosaminidase (NAG) as a clinical marker of renal tubular injury, urinary
      monocyte chemoattractant protein-1 (MCP-1) as an inflammatory marker in renal
      tubulointerstitium, and clinical markers of renal disease. Notably, serum and
      urinary adiponectin levels were significantly increased in patients with overt
      diabetic nephropathy compared to those with normoalbuminuria and
      microalbuminuria. In univariate linear regression analysis, serum adiponectin
      levels were positively correlated with serum creatinine (r = 0.648, P<0.0001),
      urinary albumin (r = 0.583, P<0.0001), urinary NAG (r = 0.406, P<0.01), urinary
      MCP-1 (r = 0.514, P<0.0001), and urinary adiponectin (r = 0.691, P<0.0001) levels
      in all diabetic patients. Urinary adiponectin levels were also positively
      correlated with serum creatinine (r = 0.729, P<0.0001), urinary albumin (r =
      0.799, P<0.0001), urinary NAG (r = 0.701, P<0.0001), and urinary MCP-1 (r =
      0.801, P<0.0001) levels in all diabetic patients. Multiple linear regression
      analysis showed that serum creatinine and urinary adiponectin levels were
      independently associated with serum adiponectin levels (r(2) = 0.522), and that
      serum creatinine, urinary NAG, urinary MCP-1, and serum adiponectin levels were
      independent determinants of urinary adiponectin levels (r(2) = 0.851). These
      results collectively indicate that renal insufficiency and tubular injury
      possibly play a contributory role in increases in serum and urinary adiponectin
      levels in overt diabetic nephropathy. We presume that an increase in circulating
      adiponectin in overt diabetic nephropathy might be a physiological response to
      mitigate renal tubular injury and to prevent the further progression of diabetic
      nephropathy through its anti-inflammatory and anti-atherogenic effects.

PMID- 16966830
TI  - Caregiver burden, health-related quality of life and coping in dementia
      caregivers: a comparison of frontotemporal dementia and Alzheimer's disease.
AB  - Frontotemporal dementia (FTD) is the second most prevalent dementia after
      Alzheimer's disease (AD). We compared 29 FTD and 90 AD caregivers with respect to
      burden, health-related quality of life (HQoL) and coping. FTD caregivers were
      more burdened than AD caregivers, and caregivers of patients who were demented
      for shorter duration had lower HQoL. We furthermore compared the 29 FTD
      caregivers with 34 caregivers of institutionalized FTD patients to understand
      their specific caregiver issues. Caregivers of FTD patients institutionalized
      after shorter dementia duration were most burdened and affected in their HQoL.
      Overall, passive coping strategies were associated with increased burden and
      decreased HQoL. We recommend that FTD caregivers be offered more support than AD
      caregivers. Furthermore, we suggest that interventions target passive coping
      strategies.

PMID- 16966831
TI  - Outcomes of cognitively impaired not demented at 2 years in the Canadian Cohort
      Study of Cognitive Impairment and Related Dementias.
AB  - BACKGROUND: People who are cognitively impaired not demented (CIND) can be at an
      increased risk for developing dementia, but little is known about the natural
      history of CIND in clinical settings. METHOD: We examined the 2-year outcome of
      CIND subjects in the Canadian Cohort Study of Cognitive Impairment and Related
      Dementias.CIND was diagnosed when at least one positive item was endorsed on the
      DSM-III-R dementia criteria, but not all criteria were met. CIND was further
      subclassified as: pre-Alzheimer's disease (pre-AD), vascular cognitive impairment
      (VCI-ND), non-AD degenerative, psychiatric, other neurologic, other medical
      conditions, mixed disorders and no etiology identified (not otherwise specified
      [NOS]). RESULT: Of 146 CIND patients with 2-year follow-up data available, 49
      (34%) progressed to dementia, while 20 (14%) recovered to not cognitively
      impaired (NCI). Progressors were significantly older than stable CIND and
      reverters (p < 0.0001; mean age = 71.1, 64.3, and 59.1, respectively), and there
      were significantly (p = 0.001) more ApoE epsilon4 carriers among progressors
      (67%) than stable CIND (29%) and reverters (12%). Pre-AD CIND and VCI-ND had the
      highest rate of conversion to dementia (41.0 and 40.0%, respectively), while
      psychiatric CIND and CIND NOS had highest rate of recovery to NCI (20.0 and
      30.0%, respectively). All conversions in pre-AD CIND were to 'probable AD'.
      CONCLUSION: CIND consists of a heterogeneous group of disorders that can be
      classified syndromically. Many subclassess - not just those with pre-AD CIND -
      are at high risk of progression to dementia, usually to Alzheimer's disease.

PMID- 16966832
TI  - Symptomatic treatment of multiple sclerosis. Multiple Sclerosis Therapy Consensus
      Group (MSTCG) of the German Multiple Sclerosis Society.
AB  - Besides immunomodulation and immunosuppression, the specific treatment of
      symptoms is an essential component of the overall management of multiple
      sclerosis (MS). Symptomatic treatment is aimed at the elimination or reduction of
      symptoms impairing the functional abilities and quality of life of the affected
      patients. Moreover, with symptomatic treatment the development of a secondary
      physical impairment due to an existing one may be avoided. Many therapeutic
      techniques as well as different drugs are used for the treatment of MS symptoms,
      but only a few of them have been investigated, especially in MS patients, and are
      approved by the national health authorities. Despite an overwhelming number of
      publications, only a few evidence-based studies exist and consensus reports are
      very rare, too. Therefore, it seemed necessary to develop a consensus statement
      on symptomatic treatment of MS comprising existing evidence-based literature as
      well as therapeutic experience of neurologists who have dealt with these problems
      over a long time. This consensus paper contains proposals for the treatment of
      the most common MS symptoms: disorders of motor function and coordination, of
      cranial nerve function, of autonomic, cognitive, and psychological functions as
      well as MS-related pain syndromes and epileptic seizures.

PMID- 16966833
TI  - Voice complaints, risk factors for voice problems and history of voice problems
      in relation to puberty in female student teachers.
AB  - The aim of the study was to estimate voice complaints, risk factors for voice
      complaints and history of voice problems in student teachers before they embarked
      on their professional teaching career. A cross-sectional questionnaire survey was
      performed among female student teachers. The response rate was 72% and 457
      questionnaires were analyzed. Voice complaints at the moment and/or during the
      past year were reported by 39.6% subjects. Subjects with voice complaints had
      significantly higher VHI scores than subjects without voice complaints. In
      comparison to subjects without voice complaints, overall, subjects with voice
      complaints reported more frequently that vocal loading factors, physical factors,
      environmental factors and psychological factors had a negative influence on their
      voice. Subjects with voice complaints reported more frequently a history of voice
      complaints during puberty and before puberty in comparison to subjects without
      voice complaints. Voice complaints in student teachers apparently had a
      multifactorial genesis and with roots during puberty or before puberty. Logistic
      regression analysis revealed that intensive voice use, emotions and history of
      voice complaints during puberty were the most discriminating set of risk factors
      for voice complaints. Subjects with voice complaints in comparison to those
      without voice complaints reported more frequently that they would develop a voice
      problem due to future teaching and that future teaching would have a negative
      influence on their voice. Around three quarters of subjects with and without
      voice complaints reported that attention paid to their voice during their
      training was sufficient. However, subjects with voice complaints were observed to
      report the need for a refresher course on voice use more frequently than those
      without voice complaints. The findings call for more intensive voice training for
      student teachers to cope with the vocal, physical and psychological demands of
      the teaching profession. Authorities should take responsibility to monitor and
      improve working conditions of student teachers and teachers.

PMID- 16966834
TI  - Fundamental frequency as a perceptual cue for vowel identification in speakers
      with Parkinson's disease.
AB  - This study investigates the importance of fundamental frequency (F0) as a
      perceptual cue for identification of vowel targets produced by speakers with
      Parkinson's disease (PD). It has been suggested in the literature that F0 is a
      redundant cue for vowel identification in highly intelligible speech. For
      speakers with dysarthria who are having difficulty with segmental and
      suprasegmental aspects of production which result in ambiguous or conflicting
      cues in the acoustic signal, F0 may have increased perceptual importance for
      accurate identification of vowel targets. In the present study, F0 contours for
      single-word targets produced in sentence level material by 20 speakers with PD
      and 20 control speakers were synthetically modified in several different ways
      (i.e., flattened and enhanced). Listener identification of vowel targets across
      the F0 conditions was recorded. The accuracy of vowel identification for the
      control group was not affected by the flattening of the F0 contour. For the
      speakers with PD, however, modification of the F0 contour (flattening or
      enhancing) affected the accuracy with which listeners identified certain vowels.
      Differences in vowel identification were found primarily for the front vowels /I,
      epsilon, ae/ along a high-low continuum.

PMID- 16966835
TI  - Tonal perceptions in normal laryngeal, esophageal, and electrolaryngeal speech of
      Mandarin.
AB  - The present study attempted to investigate if alaryngeal speakers of Mandarin
      Chinese could differentially produce the four tone levels of Mandarin: high
      level, mid-rising, falling-rising and high-falling, as perceived by native
      listeners. Syllables /ma/ and /ba/ produced at four different tone levels by 8
      normal laryngeal (NL), 7 standard esophageal (SE), and 8 electrolaryngeal (EL)
      speakers of Mandarin were perceived by 8 naive listeners. Results from the
      listening experiments showed a higher percent correct identification of tone for
      NL speech than SE and EL speech. Perceptual data showed different patterns of
      tone confusion associated with the three types of speech. SE and EL speakers were
      not able to produce the four tone levels as accurately as were NL speakers. NL
      speakers achieved a near-perfect level of accuracy in signaling tonal contrasts.
      SE speakers produced the falling-rising and high-falling tones more accurately
      than high-level and mid-rising tones, but tonal confusions existed between mid
      rising tone and falling-rising tone, and between high-level tone and high-falling
      tone. In EL phonation, high-level tone was produced more accurately than the
      other tones which were often misidentified as a high-level tone.

PMID- 16966836
TI  - Acoustic changes related to laryngeal examination with a rigid telescope.
AB  - The influence on voice quality of the insertion of endoscopic equipment with
      tongue anchoring and head position requirements during endoscopic evaluation has
      not been fully investigated. The present study attempted to examine the influence
      of: (1) the presence of a rigid endoscope and tongue anchoring, and (2) the angle
      of position technique (70-degree and 90-degree) on participants' vocal output
      during sustained production of the vowel /i/. Five acoustic measurements
      including fundamental frequency (F0) values, percent jitter values, relative
      average perturbation of F0 shimmer, and noise-to-harmonic ratios were used to
      represent participants' voice quality. Results indicated that F0 values were
      significantly influenced by the angle of sitting position, while percent jitter
      values, relative average perturbation of F0, shimmer, and noise- to-harmonic
      ratios were affected by the presence of a rigid endoscope and tongue anchoring.

PMID- 16966837
TI  - Effects of vocal training on respiratory kinematics during singing tasks.
AB  - This longitudinal study determined the effects of vocal training (VT) on
      respiratory kinematics and muscle activity during singing tasks. Four voice
      students, 3 females and 1 male, were recorded during singing tasks once a
      semester for 3 consecutive semesters. Respiratory kinematic measures included
      lung volume, rib cage (RCE) and abdominal excursions (ABE). Surface
      electromyographic measures included burst duration (BD) and peak amplitude (PA)
      of the pectoralis major, rectus abdominis and external oblique muscles.
      Descriptive statistics revealed that RCE and ABE increased from the 1st to the
      2nd semester, but decreased from the 2nd to the 3rd semester of VT. Overall, mean
      BD decreased from the 1st to the 2nd semester and increased from the 2nd to the
      3rd semester. Mean PA increased from the 1st to the 2nd semester and decreased
      from the 2nd to the 3rd semester of VT. RCE and muscle force generation of the
      above muscles increased as the demand level and the length of the phonatory tasks
      increased. Interpretation of the results suggests that the respiratory system is
      highly responsive to VT, after only 3 semesters of training.

PMID- 16966838
TI  - Analysis of the association between Apolipoprotein D and schizophrenia.
AB  - Schizophrenia is a severe, chronic and common complex debilitating mental illness
      with a large genetic component. Evidence to date suggests that apolipoprotein D
      protein may be closely related to schizophrenia. To investigate the role of the
      APOD gene in the etiology of schizophrenia, we genotyped three genetic
      polymorphisms (rs7659, rs2280520 and rs4677695) in a case-control study using
      subjects from the Chinese population, and altogether 425 cases and 473 controls
      were analyzed in the study. However, we found no significant discrepancies in
      allele and genotype frequencies of the three polymorphisms nor in the haplotype
      distribution between the cases and the controls. Our data indicate no direct
      evidence of association between schizophrenia and the APOD gene, and the results
      suggest that the three genetic polymorphisms within the APOD gene are unlikely to
      confer increased susceptibility to the illness in the Chinese population.

PMID- 16966839
TI  - Association of a functional polymorphism in the serotonin transporter gene with
      personality traits in females in a Polish population.
AB  - The aim of our study was to determine whether the 5-HTTLPR polymorphism is
      related to temperamental traits measured using the Formal Characteristics of
      Behavior - Temperament Inventory (FCB-TI) and personality traits assessed by the
      NEO Five-Factor Inventory (NEO-FFI) questionnaire. The sample comprised 200
      unrelated females, aged 18-29 years. DNA of the subjects was isolated from buccal
      epithelial cells, and 5-HTTLPR polymorphism was genotyped using PCR. The subjects
      were divided into SS, SL and LL groups according to their genotype. The
      differences in results on the endurance scale (F = 11.29, p = 0.001), measured
      using FCB-TI and neuroticism measured using NEO-FFI (F = 15.32, p = 0.000)
      between the S group (short-form allele; genotypes SS and SL) and the L group
      (long-form allele; genotype LL) were statistically significant. Additionally,
      statistically significant differences between the LL and SS groups, and between
      the SL and SS groups with respect to 'activity' (FCB-TI) were found (F = 4.5, p =
      0.012). These findings support a role of the 5-HTTLPR polymorphism in the
      modulation of personality and temperamental traits.

PMID- 16966840
TI  - Brain activation during mental maze solving.
AB  - BACKGROUND: So-called Porteus mazes are used to investigate prefrontal cortex
      (PFC) functioning in normal subjects and patients with different neuropsychiatric
      disorders. Here we present data confirming the involvement of the PFC for the
      first time by means of functional magnetic resonance imaging (fMRI). To minimize
      motor-related activation, mental mazes were used. METHODS: Mazes as well as
      pseudo-mazes without any bifurcations were presented to 49 healthy participants
      during fMRI scans. RESULTS: Both, mazes as well as pseudo-mazes, activated a
      large network from visual to parietal regions, reflecting the dorsal stream of
      visual information processing. Mazes but not pseudo-mazes also activated
      bilateral areas of the PFC indicating their special role in decision processes.
      In addition, although no motor response was required during maze performance,
      both tasks activated subcortical and cortical motor areas. CONCLUSIONS: These
      tasks are suitable for investigating and specifying PFC functioning and its
      impairment in psychiatric disorders such as schizophrenia. In addition, mental
      mazes might be a suitable task for the investigation of patients with motor
      disturbances.

PMID- 16966841
TI  - Binding and signal transduction characteristics of the nonpeptide vasopressin V1A
      receptor-selective antagonist YM218 in cultured rat mesangial cells.
AB  - Vasopressin (AVP) causes mesangial cell contraction, proliferation and
      hypertrophy. The present study investigated the effects of YM218, a potent,
      nonpeptide AVP V(1A) receptor-selective antagonist, on rat mesangial cells using
      binding, signal transduction and cell growth assays. Specific binding of (3)H-AVP
      to rat mesangial cell plasma membranes was dependent upon time, temperature and
      membrane protein concentration. Scatchard plot analysis of equilibrium binding
      data revealed the existence of a single class of high-affinity binding sites with
      the expected V(1A) receptor profile. YM218 showed high affinity for V(1A)
      receptors, exhibiting a K(i) value of 0.19 nmol/l. AVP concentration-dependently
      increased intracellular Ca(2+) ([Ca(2+)](i)) levels, stimulated mitogen-activated
      protein (MAP) kinase and induced hyperplasia. Conversely, YM218 potently
      suppressed [Ca(2+)](i) elevation, activation of MAP kinase and hyperplasia
      induced by AVP. These results indicate that YM218 displays both high affinity for
      rat mesangial cell V(1A) receptors and high potency in inhibiting AVP-induced
      signal transduction and growth response. Therefore, YM218 is a useful
      pharmacologic tool for investigating the physiologic and pathophysiologic roles
      of AVP in kidney, and may have clinical application in the prevention or
      regression of mesangial cell growth.

PMID- 16966842
TI  - Second International Conference on Pediatric Mechanical Circulatory Support
      Systems and Pediatric Cardiopulmonary Perfusion.

PMID- 16966844
TI  - Management of pediatric patients after implantation of the Berlin Heart EXCOR
      ventricular assist device.
AB  - Within the last 16 years, the Berlin Heart EXCOR systems have been used for
      circulatory support in 73 infants and children up to 17 years of age (mean, 7
      years) with severe circulatory failure resistant to pharmacological therapy at
      our institution. These were patients with cardiomyopathy, fulminant myocarditis,
      end-stage congenital cardiac defects, and acute heart failure after congenital
      heart surgery. Mean EXCOR support time was 36 days (range, 1 to 420 days). Forty
      four patients (62%) survived up to transplantation or after weaning and 37 (51%)
      of them, including 9 infants, were discharged home. These results in patients
      with very advanced disease have improved significantly during the past few years
      as the result of technical developments and growing experience in the treatment
      of patients on the device and in postoperative care. The following article gives
      answers to five questions frequently asked about intensive care unit treatment
      while on the device, anticoagulation and additional medical support during left
      ventricular or biventricular support, the daily treatment of the children, and
      options for the weaning procedure.

PMID- 16966845
TI  - Pulsatile ECMO and VAD: a dual use of a new device in pediatric cardiac patients.
AB  - The purpose of this investigation was to present the first European clinical
      experience with the new MEDOS DELTASTREAM DP1 used in pulsatile extracorporeal
      membrane oxygenation (ECMO) or ventricular assist device (VAD) options in the
      pediatric population. Between January 2002 and April 2006, 11 patients required
      ECMO and 5 patients received a left VAD (LVAD) in the San Vincenzo Hospital.
      Indications were postcardiotomy heart failure in 15 patients and fulminant
      myocarditis in one patient. ECMO was established in all patients by cannulation
      of the right atrium and ascending aorta. LVAD was instituted by cannulation of
      the left atrium and ascending aorta. The DP1, an extracorporeal rotary blood
      pump, was used as an ECMO and an LVAD device. The pump features a diagonal-flow
      impeller and can be used for both continuous and pulsatile modes of perfusion.
      Priming volume of the pump was approximately 30 ml, with a flow rate of up to 8
      l/min. Ten patients were discharged from ECMO and four from VAD. In the ECMO
      group, one patient died of peritonitis while on ECMO and two patients died on
      days 3 and 4 after weaning because of persistent pulmonary hypertension and major
      neurologic complications. In the VAD group, one patient died of low output
      syndrome 9 days after weaning. A 12-year-old patient was successfully given
      transplantation on day 8 of ECMO support and discharged on day 30 after heart
      transplant. All other patients were discharged. Three pumps were changed for pump
      failure and one pump was electively replaced because of improper anticoagulation
      management. No other thromboembolic adverse events occurred. Our results suggest
      that the MEDOS DELTASTREAM DP1 pulsatile pump system can be used as an ECMO or a
      VAD support. The opportunity to utilize pulsatile flow in postcardiotomy
      cardiogenic shock significantly improved the outcomes by producing more
      physiologic hemodynamics and superior end organ function. Easy implantation and
      simple management of this device represents the major advantage.

PMID- 16966846
TI  - Pediatric assist with the Medos and Excor systems in small children.
AB  - Pediatric long-term ventricular support with paracorporeal assist devices is
      performed in only a few institutions. We report on our experience with two
      pediatric paracorporeal devices, which have been implanted in neonates, infants,
      and small children. Seven children with ages ranging from 2 weeks to 6 years and
      a body weight of 3 to 19 kg were provided with either a Medos or a BerlinHeart
      System. The underlying heart diseases included dilative cardiomyopathy (n = 3),
      endocardial fibroelastosis (n = 2), Ebstein anomaly, and status post redo aortic
      valve replacement (n = 1). All children were in New York Heart Association class
      IV and were inotrope dependent. Three children were provided with a Medos system
      and 4 children with a BerlinHeart Excor device. In 6 cases, left ventricular
      support, and in 1 case, right ventricular support was performed. All patients
      were stabilized with univentricular mechanical support. The perioperative course
      was uneventful, and end-organ function was well recovered. Reexploration for
      bleeding and evacuation of mediastinal blood clots was necessary in all three
      neonates but not in any of the older infants. Severe thromboembolic events were
      only noticed in the neonates. Successful bridge to transplantation was performed
      in 6 of the 7 patients (87.5%). Our late results have been quite encouraging, as
      they readily prove that pediatric long-term mechanical support is possible with a
      high quality of life and an acceptable low complication rate.

PMID- 16966847
TI  - DIDECMO: a new polymethylpentene oxygenator for pediatric extracorporeal membrane
      oxygenation.
AB  - We reviewed the performance of a new polymethylpentene oxygenator (DIDECMO,
      Dideco, Mirandola, Italy) in terms of clinical safety and efficiency in priming,
      oxygenation, and oxygenator resistance in neonatal and pediatric extracorporeal
      membrane oxygenation (ECMO) patients. Between March 2005 and January 2006, 14
      patients required ECMO in the San Vincenzo Hospital. Of these, 8 (median age, 9
      days; range, 3 days to 15 months) received normothermic ECMO for postcardiotomy
      heart failure after surgery for congenital heart disease. The DIDECMO oxygenator
      was used in all patients (median weight, 2.4 kg; range, 2 to 7 kg). According to
      our previous experience, all patients received the same anticoagulation
      management. DIDECMO is a new phosphorylcholine-coated, polymethylpentene hollow
      fiber oxygenator recommended for a maximum blood flow of 2300 ml/min with a
      membrane surface area of 0.67 m2 and validated to be used up to 5 days. Static
      priming was 100 ml and mean support time 05 hours (range, 36 to 198 hours). No
      oxygenators were changed during support. Median pressure drop during overall
      assistance was 24 mm Hg. Carbon dioxide elimination was obtained with a 1:1 blood
      flow/air flow ratio. Neither oxygenator-related major nor minor adverse events
      occurred during support. In our initial experience, the new polymethylpentene
      DIDECMO oxygenator provided adequate gas exchange and offered technical
      advantages in terms of low priming volume and acceptable hemodynamic resistance
      despite pulsatile flow regimen. Also, we used this device for more than 8 days
      without any technical problems.

PMID- 16966848
TI  - Use of a novel anticoagulation strategy during ECMO in a pediatric population:
      single-center experience.
AB  - We describe a novel anticoagulation strategy with continuous intravenous
      antithrombin infusion and intermittent heparin infusion in pediatric population
      during extracorporeal membrane oxygenation (ECMO). From November 2004 through
      February 2006, 11 patients required ECMO for postcardiotomy cardiorespiratory
      failure. The mean duration of support time was 112 hours (range 68-192 hours).
      Since April 2005, we modified our anticoagulation protocol in the last six
      patients. Continuous antithrombin infusion was started immediately after surgery
      based on the lab result. The antithrombin level was maintained >100% using the
      following formula: 100 (target value) - (Antithrombin value on lab test) x weight
      in 4 hours. Antithrombin value was checked at 4-hour intervals. Heparin infusion
      was started when the antithrombin value was > 100% and remained stable for more
      than 12 hours and the amount of bleeding was < 2 ml/kg for more than 3
      consecutive hours; then heparin infusion was started at 2 UI/kg/h via the
      oxygenator (target ACT was not < 150 seconds). Three patients in the first group
      died. Eight patients were weaned and discharged; the third, fourth, and fifth
      required surgical revision for bleeding. One experienced minor neurologic
      sequelae. Neither surgical revision nor thromboembolic complications occurred in
      the new anticoagulation group. A novel anticoagulation strategy utilizing
      continuous intravenous antithrombin and intermittent heparin infusion reduced
      significantly surgical revision for bleeding in the first 48 hours. This has
      translated into excellent overall outcomes.

PMID- 16966849
TI  - Trans-hepatic cannulation: a novel approach for placement of a pediatric
      percutaneous ventricular assist device.
AB  - Pediatric ventricular assist device (VAD) use is increasing. The TandemHeart PTVA
      system is a percutaneous VAD used in adults. Pediatric use is limited by cannula
      size. Trans-hepatic left atrial (LA) cannulation offers the possibility of
      shorter, larger-diameter cannulae, but specific requirements for cannula size and
      flow characteristics need to be developed. We evaluated the feasibility of trans
      hepatic cannulation based on patient measurements and bench-top modeling. Two
      hundred patients admitted to the University of Michigan Pediatric CICU were
      evaluated. Patients over 14 years and dextrocardiac patients were excluded. The
      distance from the skin between the 10th and 11th ribs at the mid-axillary line to
      the left-heart border was measured on x-ray. LA size was measured on
      echocardiogram. From these measurements, prototype cannulae were fabricated.
      Benchtop testing of developed cannulae was performed with a pump speed of 8500
      RPM and fluid viscosity of 4.0 cP at physiologic atrial and arterial pressures.
      Inlet pressure and deliverable flows were measured. The proposed design delivered
      sufficient flow with negative pressures low enough to avoid hemolysis. Trans
      hepatic LA cannulation for percutaneous VAD placement is feasible. The shorter
      distance to the LA and larger hepatic vein size allows design of pediatric
      appropriate cannulae with adequate flow rates.

PMID- 16966850
TI  - Use of dilutional ultrasound monitoring to detect changes in recirculation during
      venovenous extracorporeal membrane oxygenation in swine.
AB  - Since recirculation during venovenous extracorporeal membrane oxygenation (VV
      ECMO) reduces oxygen delivery to the patient, monitoring recirculation is
      necessary to guide clinicians in interventions that may reduce recirculation and
      thereby optimize patient care. The use of dilutional ultrasound may be a
      clinically practical way to quantify recirculation during VV ECMO. This study
      evaluates in a swine model of VV ECMO a dilutional ultrasound techniques ability
      to provide accurate recirculation data under changing conditions. One 16-kg swine
      was cannulated with a dual-lumen cannula and placed on VV ECMO. Recirculation
      measured by using blood oxygen saturations (r = S(preox) - SVO2/S(postox) - SVO2)
      was compared with recirculation measured by a saline dilution ultrasound
      technique. Dilutional ultrasound was then used to measure changes in baseline
      recirculation in the face of (a) cannula repositioning and (b) a drug-induced
      cardiac output change. The comparison of recirculation calculations between the
      saturation method and dilutional ultrasound were similar at all flow rates
      measured. The time for results was much faster with the use of dilutional
      ultrasound. Induction of recirculation changes by repositioning the cannula or
      changing cardiac output was rapidly detected using dilutional ultrasound and
      showed significant differences from baseline recirculation. Dilutional ultrasound
      provides a clinically practical method to quantify and monitor recirculation in
      VV ECMO applications and may aid in assessing interventions to improve oxygen
      delivery.

PMID- 16966851
TI  - Pediatric mechanical circulatory support in the United States: past, present, and
      future.
AB  - Mechanical support of the failing myocardium has become standard therapy for
      adults who fail medical management. Historically, there have been fewer options
      for children with heart failure. Extracorporeal membrane oxygenation and
      centrifugal pump-based ventricular assist devices have been the most commonly
      used circulatory support modalities for pediatrics in the United States. During
      the last few years, substantial advances in pediatric circulatory support have
      been made, with greater availability of a number of devices suitable for
      pediatrics. For example, there has been increasing experience using the DeBakey
      VAD Child and the Berlin Heart VAD to provide circulatory support for children
      during this period. A number of innovative devices under development supported by
      the Pediatric Circulatory Support Program of the National Heart, Lung, and Blood
      Institute hold great promise for expanded options for pediatric mechanical
      circulatory support in the future.

PMID- 16966852
TI  - Effects of pulsatile and nonpulsatile perfusion on vital organ recovery in
      pediatric heart surgery: a pilot clinical study.
AB  - The use of pulsatile flow during cardiopulmonary bypass (CPB) with regard to
      improved patient outcomes is controversial. We evaluated pulsatile perfusion in
      pediatric patients undergoing CPB in a clinical setting. Fifty consecutive
      pediatric patients undergoing open heart surgery for repair of congenital heart
      disease were prospectively entered into the study and randomly assigned to either
      the pulsatile perfusion group (group P, n = 25) or the nonpulsatile perfusion
      group (group NP, n = 25). Study parameters included intubation time, duration of
      intensive care unit (ICU) stay and hospital stay, need for inotropic support,
      preoperative and postoperative enzymes, creatinine, C-reactive protein, blood
      count, mean urine output, and total drainage. Group P, compared with group NP,
      had significantly less inotropic support (number of agents, 1.48 +/- 1.05 versus
      2.44 +/- 1.03, p = 0.0015; dopamine, 6.48 +/- 3.27 versus 10.3 +/- 4.8 microg/kg
      per minute, p = 0.0023; dobutamine, 3.12 +/- 6.55 versus 8.03 +/- 9.1 microg/kg
      per minute, p = 0.034), shorter intubation period (20.36 +/- 17.02 versus 35.44
      +/- 30.72 hours, p = 0.038), and shorter duration of ICU stay (2.16 +/- 1.07
      versus 4.32 +/- 4.21 days, p = 0.028) and hospital stay (7.64 +/- 2.48 versus
      11.84 +/- 6.82 days, p = 0.007). There were no significant differences in
      creatinine, enzyme levels, or drainage amounts between the two groups. Higher
      urine output during CPB (553.6 +/- 150.89 versus 465.8 +/- 151.23 ml/d, p =
      0.045) and during the ICU period (658.8 +/- 210.99 versus 528,2 +/- 224.71 ml/d,
      p = 0.039) was observed in group P compared with group NP. We concluded that the
      use of pulsatile flow resulted in improved patient outcome in preserving cardiac
      function and maintaining better renal and pulmonic function (shorter intubation
      period) in the early postbypass period.

PMID- 16966853
TI  - Continuous cerebral and myocardial perfusion during aortic arch repair in
      neonates and infants.
AB  - To minimize myocardial ischemia, we repaired aortic arch obstruction with
      ventricular septal defect, using two different techniques of cerebral and
      myocardial perfusion. Seventy-one infants, ages 3 to 137 days, underwent primary
      repair of coarctation of the aorta (n = 49)/interruption of the aortic arch (n =
      22) with ventricular septal defect. In 65 patients, an end-to-end arch
      anastomosis was performed with cerebral and myocardial perfusion through the
      innominate or the ascending arterial cannula (non-working beating heart: NWBH).
      In the remaining 6 patients, an arterial cannula was placed into the innominate
      artery. With partial cardiopulmonary bypass, the innominate artery was snared
      proximal to the cannulation site and the ascending aorta was cross-clamped. An
      extended arch anastomosis was carried out with cerebral perfusion and a working
      beating heart (WBH). Ten patients (15%) undergoing aortic arch repair with the
      NWBH technique required cardioplegic arrest to complete a proximal anastomosis,
      whereas in all 6 repairs with the WBH technique, the extended anastomoses were
      completed without myocardial ischemia. One hospital death and late death
      occurred, with an overall survival of 98%. End-to-end arch reconstruction is
      feasible without myocardial ischemia, using the NWBH technique in patients
      without hypoplastic arch and using the WBH technique in patients with hypoplastic
      arch.

PMID- 16966854
TI  - Normothermic bypass in pediatric surgery: technical aspect and clinical
      experience with 1400 cases.
AB  - We analyzed our experience with warm perfusion and blood cardioplegia in
      pediatric surgery. Warm surgery was performed in 1400 patients. Prime and
      perfusate are kept at 37 degrees C before and during bypass and intermittent warm
      blood cardioplegia is used for myocardial protection. Analyzed parameters were:
      perioperative blood gas, hydric balance of cardioplegia, spontaneous resumption
      of rhythm after aortic unclamping, troponin I level, postoperative neurologic and
      renal function, duration of mechanical ventilation (five diagnostic groups), and
      duration of intensive care unit (ICU) stay. Satisfactory gas exchange is the
      rule, and fluid addition is negligible during warm cardioplegia. Spontaneous
      resumption of sinus rhythm occurred in 99% of patients, Troponin I elevation was
      < 10 ng/ml in 46% of cases. Prevalence of neurologic complications (0.3%) and of
      renal insufficiency treated by peritoneal dialysis (0.35%) favorably compares
      with data reported in the literature. Average mechanical ventilation time was <
      48 hours in each diagnostic group. Duration of ICU stay was < 48 hours in 86% of
      the 1400 patients. In our experience, normothermic surgery is an excellent
      alternative to hypothermia.

PMID- 16966855
TI  - Atrial natriuretic peptide: could it be a marker for postoperative recurrent
      effusions after Fontan circulation in complex congenital heart defects?
AB  - Fontan operation and its modifications are used for the physiological correction
      of complex congenital heart malformations with functionally single ventricle.
      Atrial natriuretic peptide (ANP), a physiological diuretic and vasodilator that-
      together with the effects of cardiopulmonary bypass--plays an important role in
      the augmentation of capillary permeability in Fontan patients. The rise in right
      atrial pressure and wall stress is an important stimulus for the release of ANP.
      ANP levels were measured before and early after surgery in Fontan group (n = 20)
      and control group (n = 20, patients with simple cardiac defects) to study its
      influence on and association with mean right atrial pressure, pulmonary vascular
      resistance (PVR), systemic vascular resistance, amount of drainage during early
      and late postoperative period, duration of intensive care unit and hospital stay,
      and need for colloid supplement. Early postoperative ANP values showed a negative
      correlation with PVR (r = -0.55) and total drainage (r = -0.88). There was no
      significant change in ANP during surgery or in the postoperative period in
      control patients. Reduction of PVR and maintenance of efficient urine output are
      important in the management of Fontan circulation. We conclude that high levels
      of ANP measured early after Fontan operation can be used as a marker for the
      successful establishment of Fontan circulation in patients with complex
      congenital heart defects.

PMID- 16966856
TI  - Advantages of temporary venoatrial shunt using centrifugal pump during
      bidirectional cavopulmonary shunt.
AB  - Single-ventricle palliation without the use of cardiopulmonary bypass carries
      advantages that reduce systemic edema and inflammatory responses; however, simple
      clamping of the superior vena cava (SVC) without a temporary shunt leads to
      increase in cerebral venous pressure and subsequent decrease in cerebral blood
      flow during bidirectional cavopulmonary shunt (BCPS). We report our experience of
      BCPS, using a centrifugal pump-assisted temporary shunt. The criteria included an
      unrestrictive interatrial communication, the absence of atrioventricular valve
      regurgitation, and the existence of an antegrade pulmonary blood flow. From
      August 2000, 14 children with single-ventricle physiology met the criteria. The
      mean age was 1.0 +/- 0.9 years, and the mean weight was 8.4 +/- 2.6 kg. A
      temporary shunt was established between the SVC and the right atrium with right
      angle cannulae, which were connected to a centrifugal pump to accelerate the
      blood flow from the SVC to the right atrium. All patients tolerated the
      procedure. Mean central venous pressure was 17 +/- 4 mm Hg, and transcutaneous
      oxygen saturation was maintained at 77 +/- 8% during anastomosis. No patients
      required blood transfusion. There were no postoperative neurological
      complications. The centrifugal pump-assisted temporary shunt offered safer and
      more effective circulatory support than other shunt systems, with excellent
      venous drainage in pediatric patients undergoing BCPS.

PMID- 16966857
TI  - Mortality as an outcome parameter for pediatric heart surgery.
AB  - Public interest in the performance of pediatric cardiac surgery programs is
      increasing. Mortality is the focus of outcomes reporting in pediatric cardiac
      surgery due both to its importance as an outcome and its accessibility in
      clinical and administrative data. However, assessment of mortality rates in
      congenital cardiac surgery is more complex than in adult cardiac surgery due to
      the wider range of procedures performed and the low frequency at which each
      individual procedure is performed. In order to accurately describe mortality, one
      must understand types of databases, data definitions, and risk adjustment
      methods. We review the risk adjustment methodologies and data sources used to
      produce mortality statistics. In addition, the issues of data quality and
      defining mortality are discussed.

PMID- 16966858
TI  - Seven years' experience of pediatric cardiopulmonary bypass: 8685 cases in
      Shanghai Children's Medical Center.
AB  - Herein we report our 7-year-experience of cardiopulmonary bypass. Between April
      1, 1999, and December 31, 2005, 8685 children with congenital heart disease
      underwent cardiopulmonary bypass in Shanghai Children's Medical Center. The
      number of cases increased every year, and the number of patients younger than 1
      year or weighing <10 kg also increased. Different bypass technology was adapted
      according to the operation. Roller pumps were used for most of the patients.
      Crystal cardioplegia (St. Thomas II) was used until blood cardioplegia was
      introduced in 2003. Ultrafiltrators were set up for infants weighing <10 kg.
      Mortality rates per year ranged from 1.81% to 3.70%. The most frequent
      complication was low cardiac output, about 12% in recent years. Arrhythmia,
      infection, and lung complications were the next three most frequent problems
      after surgery.

PMID- 16966859
TI  - Mechanical valve replacement of the systemic atrioventricular valve in children.
AB  - In children with systemic atrioventricular valve disease (SAVVD), reconstructive
      surgery is the primary goal. However, in cases with severely dysplastic valves or
      failed repair, valve replacement is the only option. The purpose of this study
      was to assess the early and late outcome following mechanical valve replacement
      in SAVVD. Between 1989 and 2003, 31 children underwent mechanical valve
      replacement (19 St. Jude Medical, 12 Carbomedics) in SAVVD (27 mitral, 3
      tricuspid in corrected transposition of the great arteries, 1 common in an
      univentricular heart) at our institution. The ages ranged from 3 months to 15
      years (mean 4 years) and body weight varied between 4.2 and 57 kg (mean 13.3 kg).
      The size of prostheses ranged between 16 and 31 mm (mean 23.9 mm). The main
      indication for valve replacement was severe insufficiency of left
      atrioventricular valve (84%); 84% of the patients had had a previous cardiac
      operation. The overall hospital mortality was 6.5% The mean follow up was 7.7
      years (range 2-13 years). Ninety percent of children represent sinus rhythm, 87%
      are in NYHA class I. All patients were placed on a regimen of Phenprocoumon
      aiming to maintain the international normalized ratio (INR) between 3.0 and 4.0.
      Since 1994, INR self-management of oral anticoagulation was performed either by
      the patient or his or her parents. There was no anticoagulation-related
      complication in this patient group. Mechanical valve replacement in left
      atrioventricular valve disease carries a low operative risk across the spectrum
      of pediatric age despite previous operations in most cases. Long-term survival
      and quality of life are good in nearly all cases. The rate of anticoagulation
      related complications is very low, especially when INR self management is
      performed.

PMID- 16966860
TI  - Plasma proteomics: a noninvasive window on pathology and pediatric cardiac
      surgery.
AB  - A challenge of pediatric research is the limited ability to obtain tissue samples
      from small patients. To confront this problem, blood biomarkers can be used as
      surrogate markers of disease processes and aid in patient monitoring and disease
      detection. Furthermore, proteomic analysis of plasma samples is one approach for
      large-scale discovery of disease biomarkers. This study examined the use of
      plasma for disease process biomarkers in pediatric patients undergoing
      cardiopulmonary bypass (CPB) surgery. Proteomic studies of plasma are limited by
      the presence of a few high abundance proteins that mask the presence of lower
      abundance proteins of interest. Plasma immunoaffinity depletion (removing 6 of
      the highest abundance proteins of little pathological importance) increases
      sensitivity of detection for proteins such as those related to inflammation,
      remodeling, and damage. Using two-dimensional in-gel fluorescence
      electrophoresis, changes in the expression levels of proteins that occur as a
      result of CPB can be identified. In the present study, plasma depletion removed
      83% of the plasma protein mass, allowing approximately 1400 spots to be observed
      by two-dimensional in-gel fluorescence electrophoresis. Of the detected spots, 79
      (5.7%) were altered by CPB. These data illuminate the strength of plasma
      proteomics in identification of candidate biomarkers of CPB-associated disease
      processes.

PMID- 16966861
TI  - Development of standard tests to examine viscoelastic properties of blood of
      experimental animals for pediatric mechanical support device evaluation.
AB  - We investigated the applicability of measuring the viscoelasticity of bovine,
      ovine, and porcine whole blood for the evaluation of sublethal damage to red
      blood cells (RBCs). An increase in blood viscosity and elasticity without changes
      in hematocrit and plasma viscosity would signify a decrease in RBC deformability.
      Blood viscoelasticity was assessed using a Vilastic Scientific viscoelastometer.
      Due to the natural absence of RBC aggregation and small RBC size in normal bovine
      and ovine blood, viscoelastic properties are less readily detected. However, we
      found that adjustment of blood hematocrit to a standard level of 40-50% allows
      for sensitive assessment of viscoelasticity in these blood types demonstrating a
      marked non-Newtonian behavior mostly related to RBC deformability. Porcine blood
      showed a pronounced non-Newtonian behavior at all tested hematocrit values, which
      makes it rheologically comparable to human blood. Both viscosity and elasticity
      were elevated after blood exposure to a uniform mechanical stress. RBCs
      rigidified by heat exposure demonstrated a loss of viscoelasticity dependence on
      shear rate. Measurements of blood viscoelasticity can be meaningful in bovine,
      ovine, and, especially, porcine blood, and can be used for evaluation of
      sublethal blood damage during in vitro and animal trials of heart-assist devices.

PMID- 16966862
TI  - Novel "biomechanical" polymeric valve prostheses with special design for aortic
      and mitral position: a future option for pediatric patients?
AB  - In children, systemic heart valve replacement with bioprostheses is associated
      with accelerated valve degeneration, and mechanical prostheses require permanent
      anticoagulation. Novel "biomechanical" polymeric valve prostheses ("bio" =
      flexible, "mechanical" = synthetic), solely made of polycarbonate urethane (PCU),
      were tested in vitro and in a growing animal (calf) model with the aim of
      improved durability without permanent anticoagulation. The trileaflet aortic
      prosthesis has diminished pressure loss and reduced stress and strain peaks. The
      asymmetric bileaflet mitral valve mimics natural nonaxial inflow. The valves
      underwent long-term in vitro testing and in vivo testing in growing calves for 20
      weeks [mitral (7), aortic (7)] with comparison to different commercial
      bioprostheses [mitral (7), aortic (2)]. In vitro durability of PCU valves was
      proved up to 20 years. Survival of PCU valves versus bioprostheses was 7 versus 2
      mitral and 5 versus 0 aortic valves, respectively. Two animals with PCU aortic
      valves died of pannus overgrowth causing left ventricular outflow tract
      obstruction. Degeneration and calcification were mild (mitral) and moderate
      (aortic) in PCU valves but were severe in biological valves. There was no
      increased thrombogenicity of the PCU valves compared to bioprostheses. The novel
      polymeric valve prostheses revealed superior durability compared to current
      bioprostheses in growing animal model without permanent anticoagulation and thus,
      may be a future option for pediatric patients.

PMID- 16966863
TI  - The PediPump: development status of a new pediatric ventricular assist device:
      update II.
AB  - The PediPump is a new ventricular assist device with a hydraulic output range
      designed for children from newborn infants to adolescents. The design is based on
      a mixed-flow rotary pump; the rotating assembly consists of a front impeller,
      front and rear radial magnetic bearings, and a central motor magnet. Two
      different implantable pumps were designed initially: an intravascular pump
      measuring 7 x 75 mm and an extravascular pump measuring 14 x 85 mm. Current
      prototypes are substantially smaller: The current intravascular version measures
      4.5 x 55 mm, whereas the current extravascular version measures 11 x 70 mm. Both
      devices provide pressure and flows capable of supporting adults, far exceeding
      the initially defined physiologic requirements for children weighing 2 to 25 kg.
      This basic pump design may be used in acute or chronic clinical settings to
      provide right ventricular, left ventricular, or biventricular support. There are
      three objectives for the PediPump development program: 1) determination of basic
      engineering requirements for hardware and control logic including design analysis
      for system sizing, evaluation of control concepts, and bench testing of
      prototypes; 2) performance of preclinical anatomic fitting studies using CT-based
      3D modeling; and 3) animal studies to provide characterization and reliability
      testing of the device.

PMID- 16966864
TI  - Model of pCO2 gap during hypothermic cardiopulmonary bypass.
AB  - Perfusion adequacy during cardiopulmonary bypass is important in reducing
      postoperative morbidity. The pCO2 gap (defined as the difference between blood
      and tissue pCO2 levels) has been shown to be a sensitive measure of ischemia
      resulting from inadequate perfusion in pediatric patients undergoing deep
      hypothermic cardiac arrest. The complexity of measuring tissue pCO2 levels has
      motivated development of a mathematical model to provide an indirect indication
      of pCO2 gap. The model allows us to examine relations between tissue pCO2, plasma
      pCO2, and the rate of CO2 removal through the extracorporeal oxygenator. Three
      compartments have been modeled with CO2 generation and mass transfer coefficients
      estimated on the basis of published correlations with height and weight. Model
      predictions have been compared with oxygenator exhaust measurements taken during
      a hypothermic cardiac procedure. The model predicts carbon dioxide buildup in the
      tissues during hypothermia followed by equilibration with the blood on rewarming.
      The model appears to qualitatively predict CO2 removal rates observed during deep
      hypothermic cardiac arrest. Refinement and validation of the model may lead to a
      tool for predicting tissue pCO2 levels during and after hypothermic
      cardiopulmonary bypass.

PMID- 16966865
TI  - Hemodynamic energy generated by a combined centrifugal pump with an intra-aortic
      balloon pump.
AB  - We examined the pulsatility generated by an intra-aortic balloon pump/centrifugal
      pump (IABP/CP) combination in terms of energy equivalent pressure (EEP) and
      surplus hemodynamic energy (SHE). In five cardiac-arrested pigs, the outflow
      cannula of the CP was inserted into the ascending aorta, the inflow cannula in
      the right atrium. A 30-ml IABP was subsequently placed in the descending aorta.
      Extracorporeal circulation was maintained for 30 minutes using a pump flow of 75
      ml/kg per minute by CP alone or by IABP/CP with pressure and flow measured in the
      right internal carotid artery. The IABP/CP combination converted the flow to
      pulsatile and increased pulse pressure significantly from 9.1 +/- 1.3 mm Hg to
      54.9 +/- 6.1 mm Hg (p = 0.012). It also significantly increased the percent
      change from mean arterial pressure to EEP from 0.2 +/- 0.3% to 23.3 +/- 6.1% (p =
      0.012) and SHE from 133.2 +/- 234.5 erg/cm to 20,219.8 +/- 5842.7 erg/cm3 (p =
      0.012). However, no statistical difference was observed between CP and IABP/CP in
      terms of mean carotid artery pressure (p = NS). In a cardiac-arrested animal
      model, pulsatility generated by a IABP/CP combination may be effective in terms
      of energy equivalent pressure and surplus hemodynamic energy.

PMID- 16966866
TI  - Comparison of coronary artery blood flow and hemodynamic energy in a pulsatile
      pump versus a combined nonpulsatile pump and an intra-aortic balloon pump.
AB  - We compared the coronary artery blood flow and hemodynamic energy between
      pulsatile extracorporeal life support (ECLS) and a centrifugal pump (CP)/intra
      aortic balloon pump (IABP) combination in cardiac arrest. A total cardiopulmonary
      bypass circuit was constructed for six Yorkshire swine weighing 30 to 40 kg. The
      outflow cannula of the CP or a pulsatile ECLS (T-PLS) was inserted into the
      ascending aorta, and the inflow cannula of the CP or T-PLS was placed into the
      right atrium. A 30-ml IABP was subsequently placed in the descending aorta.
      Extracorporeal circulation was maintained for 30 minutes with a pump flow of 75
      ml/kg per minute by a CP with an IABP or T-PLS. Pressure and flow were measured
      in the right internal carotid artery. The energy equivalent pressure (EEP) and
      surplus plus hemodynamic energy (SHE) were recorded. The left anterior descending
      coronary artery flow was measured with an ultrasonic coronary artery flow
      measurement system. The percent change of the mean arterial pressure to EEP was
      effective in both groups (23.3 +/- 6.1 in CP plus IABP vs. 19.8 +/- 6.2% in T
      PLS, p = NS). The SHE was high enough in the CP/IABP and the T-PLS (20,219.8 +/-
      5824.7 vs. 13,160.2 +/- 4028.2 erg/cm3, respectively, p = NS). The difference in
      the coronary artery flow was not statistically significant at 30 minutes after
      bypass was initiated (28.2 +/- 9.79 ml/min in CP plus IABP vs. 27.7 +/- 9.35
      ml/min in T-PLS, p = NS).

PMID- 16966867
TI  - Hurricane Katrina: emergent interstate transport of an evacuee on biventricular
      assist device support.
AB  - In many U.S. hospitals, mechanical circulatory support has become routine.
      However, catastrophes such as Hurricane Katrina test the abilities of a hospital
      system to sustain patients on such support and transport them in emergent
      situations. A 15-year-old boy with dilated cardiomyopathy who was receiving
      biventricular mechanical circulatory support at a New Orleans hospital was
      successfully transported by Angel One Transport from Arkansas Children's Hospital
      across state lines to Texas Children's Hospital, where he was stabilized and
      received an orthotopic heart transplant.

PMID- 16966868
TI  - Unrehearsed circuit failure during neonatal ECMO: critical trans-heat exchanger
      pressure.
AB  - A newborn infant who could not be weaned from bypass after undergoing corrective
      surgery for atrioventricular septal defect was placed on arteriovenous
      extracorporeal membrane oxygenation (ECMO). Thirty-six hours later, a sudden
      violent gush of water was observed from the heater cooler system at the point
      where the outlet tubing had become detached from the machine. It was quickly
      established that this event had been caused by a massive pressure buildup at the
      integrated ECMO heat exchanger. A series of attempts were made to identify the
      cause of the problem and so rectify the situation: changing the heater cooler
      system, reversal of water flow through the heat exchanger, and, finally,
      insertion of a bridge between the outlet and inlet water tubing to moderate flow
      through the device. A complete circuit change-out and the associated risks were
      thus avoided, and the patient was successfully weaned from ECMO after 83 hours.
      Subsequent analysis of this incident identified three key elements as factors in
      this systems failure: heater cooler system cleaning protocol, heat exchange
      device construction, and incongruous heater cooler system application, which,
      together under these exact conditions, contributed to creating a situation with
      the realistic potential for a negative outcome.

PMID- 16966869
TI  - Left ventricular assist device for pediatric postcardiotomy cardiac failure.
AB  - Children with postcardiotomy heart failure who are unresponsive to maximal
      medical management have limited options for survival. Short-term mechanical
      circulatory support, such as with extracorporeal membrane oxygenation and
      ventricular assist devices, has assumed an expanding role in the care of these
      patients by providing a bridge to recovery. This report describes the use of left
      ventricular assist devices with centrifugal pumps in five pediatric cases (weight
      <15 kg) with postcardiotomy heart failure.

PMID- 16966870
TI  - Acute myocardial infarction in a young adult: a case report and literature
      review.
AB  - Sudden cardiac death related to sports in young patients can have many causes.
      Hypertrophic cardiomyopathy, congenital coronary abnormalities, and myocarditis
      make up about half of the causes of sudden cardiac death after sports. Screening
      for all athletes is important to prevent such episodes. This involves yearly
      examinations including clinical examinations, stress echocardiograms,
      echocardiography, and laboratory investigations. Also, behavioral follow up
      should be addressed, as cocaine administration and doping can both lead to
      cardiac problems and sudden cardiac death after sports. We present a case of a 17
      year-old boy who collapsed after an ice hockey competition as a result of an
      acute myocardial infarction, which was first represented by ventricular
      fibrillation. We also review the main causes of sudden cardiac death in such
      young athletes and the main investigations that have to be performed to reach the
      proper diagnosis and etiology of the condition.

PMID- 16966871
TI  - Transcranial Doppler-revealed retrograde cerebral artery flow during Norwood 1
      operation.
AB  - We describe a 6-week-old girl with a hypoplastic left heart syndrome in whom
      multimodal neuromonitoring was used during Norwood stage I palliation. After
      placement of modified Blalock-Taussig shunt, transcranial Doppler measurements
      revealed retrograde flow in the right middle cerebral artery throughout the
      cardiac cycle. Further examination showed that the change in cerebral blood flow
      was secondary to shunt runoff and clinical correlation was noted in near infrared
      spectroscopy measurements of regional cerebral oxygenation saturation. The
      surgical procedure was subsequently modified with a return of antegrade flow. We
      offer this case as one of the first (if not the first) documented case reports of
      an intraoperative modification of surgical procedure driven by changes identified
      by multimodal neuromonitoring.

PMID- 16966872
TI  - Radiation shielding design of a new tomotherapy facility.
AB  - It is expected that intensity modulated radiation therapy (IMRT) and image guided
      radiation therapy (IGRT) will replace a large portion of radiation therapy
      treatments currently performed with conventional MLC-based 3D conformal
      techniques. IGRT may become the standard of treatment in the future for prostate
      and head and neck cancer. Many established facilities may convert existing vaults
      to perform this treatment method using new or upgraded equipment. In the future,
      more facilities undoubtedly will be considering de novo designs for their
      treatment vaults. A reevaluation of the design principles used in conventional
      vault design is of benefit to those considering this approach with a new
      tomotherapy facility. This is made more imperative as the design of the
      TomoTherapy system is unique in several aspects and does not fit well into the
      formalism of NCRP 49 for a conventional linear accelerator.

PMID- 16966873
TI  - Influence of alpha and gamma radiations and non-radiation risk factors on the
      incidence of malignant liver tumors among Mayak PA workers.
AB  - This Mayak worker-based study focuses on evaluating possible associations between
      malignant liver cancers and chronic alpha irradiation, chronic gamma irradiation,
      and non-radiation risk factors (alcohol consumption, smoking, viral hepatitis,
      chemical exposure, and chronic digestive diseases). This is the first
      multivariate study related to liver cancer among Mayak workers. The study was
      performed using the nested, case-control approach and includes 44 cases of
      malignant liver tumors diagnosed from 1972 to 1999, and 111 matched controls.
      Adjusted odds ratio (OR(ad)) was evaluated relative to a group of workers with
      alpha radiation doses to liver (D(alpha)) < 2.0 Gy. Dose estimates of D(alpha) >
      2.0 Gy (corresponding (239)Pu body burden estimates >20.4 kBq) were significantly
      associated (p < 0.003) with the occurrence of hemangiosarcomas (HAS) but only
      marginal significance (0.05 < p < 0.1) was found for hepatocellular cancers
      (HCC). The ORad for HAS was 41.7 [95% confidence interval (CI): 4.6, 333] for a
      group with D(alpha) in the range >2.0-5.0 Gy and was 62.5 (7.4, 500) for a group
      with D(alpha) > 5.0-16.9 Gy. The attributable risk (AR) was calculated as 82%.
      For HCC, O(Rad) was estimated as 8.4 (0.8, 85.3; p < 0.07) for a group with
      D(alpha) in the range >2.0-9.3 Gy. For the indicated group, the AR was 14%. An
      association with high external gamma-ray doses (D(gamma)) to the total body was
      revealed for both HCC and for combined liver cancers when dose was treated as a
      continuous variable. However, we find no evidence that chronic low doses of gamma
      rays are associated with liver cancer occurrence. Cholangiocarcinoma (CHC) was
      not associated with either alpha- or gamma-ray exposure. As expected, an
      association between alcohol abuse and HCC was inferred [O(Rad) = 3.3 (1.2, 9); AR
      = 41%] but not for CHC or HAS.

PMID- 16966874
TI  - A novel technique for the rapid identification of alpha emitters released during
      a radiological incident.
AB  - Before the May 2003 TOPOFF II exercise in Seattle, the U.S. EPA's Laboratory in
      Las Vegas prepared five spiked samples to be analyzed by the Washington State
      Department of Health's (WSDOH) Radiation Laboratory. Two of these were simulated
      deposition samples prepared on packaging tape. Laboratories throughout the world
      are investigating rapid methods for analyzing plume-borne radioactive materials.
      While measuring gamma emitters in environmental samples is fairly
      straightforward, the potential presence of alpha emitters adds complexity. The
      short range of alpha particles and the high degree of energy interference between
      nuclides usually require chemical separations and very thin mounts for alpha
      spectrometry. Work published on Frisch-Grid alpha counting of transuranics in
      soil and the commercial development of radon-rejection for air filters indicate
      that alpha spectrometry can be used directly on some media with success. This
      suggests that plume-borne material sampled from air or freshly deposited surface
      layers may be counted directly by alpha spectrometry, making it possible to
      identify both alpha and gamma emitters and determine their relative
      concentrations. The long-range objective is to propose a sampling method that can
      be used for rapid qualitative and semi-quantitative analyses using conventional
      radioanalytical instruments, with minimal preparation. This paper describes
      experimentation with this approach during a real-time exercise. All samples were
      prepared by spiking with (137)Cs, (241)Am, (238)Pu, and (239)Pu and presented to
      the WSDOH's Radiation Laboratory for analysis during TOPOFF II. The laboratory
      quickly identified and determined the ratios of all four contaminants on the tape
      samples using sequential alpha spectrometry and gamma-ray spectroscopy without
      chemical separations.

PMID- 16966875
TI  - Nuclear security and radiological preparedness for the olympic games, athens
      2004: lessons learned for organizing major public events.
AB  - In light of the exceptional circumstances that arose from hosting the Olympic
      Games in Athens in 2004 and from recent terrorist events internationally, Greece
      attributes the highest priority to security issues. According to its statutory
      role, the Greek Atomic Energy Commission is responsible for emergency
      preparedness and response in case of nuclear and radiological events, and advises
      the Government on the measures and interventions necessary to protect the public.
      In this context, the Commission participated in the Nuclear, Radiological,
      Biological, and Chemical Threat National Emergency Plan, specially developed for
      the Olympic Games, and coordinated by the Olympic Games Security Division. The
      objective of this paper is to share the experience gained during the organization
      of the Olympic Games and to present the nuclear security program implemented
      prior to, during, and beyond the Games, in order to prevent, detect, assess, and
      respond to the threat of nuclear terrorism. This program adopted a multi-area
      coverage of nuclear security, including physical protection of nuclear and
      radiological facilities, prevention of smuggling of radioactive materials through
      borders, prevention of dispersion of these materials into the Olympic venues,
      enhancement of emergency preparedness and response to radiological events,
      upgrading of the technical infrastructure, establishment of new procedures for
      assessing the threat and responding to radiological incidents, and training
      personnel belonging to several organizations involved in the National Emergency
      Response Plan. Finally, the close cooperation of Greek Authorities with the
      International Atomic Energy Agency and the U.S. Department of Energy, under the
      coordination of the Greek Atomic Energy Commission, is also discussed.

PMID- 16966876
TI  - Effective dose scaling factors for use with uranium series cascade impactor data:
      a reassessment using the IMBA code.
AB  - Air sampling with a multi-stage cascade impactor enables one to assess airborne
      radioactivity as a function of particle size, significantly enhancing the
      accuracy of the dose assessment. The application of cascade sampling data to
      inhalation dose assessments can require more computational effort if something
      other than a mono-sized distribution per impactor stage is to be considered. To
      overcome this limitation, Kim et al. (Health Phys 89:359-374; 2005) introduced
      the concept of an effective dose scaling factor SF(E) enabling one to consider
      more realistic impactor stage radioactivity distributions (uniform, linearly
      decreasing, or linearly increasing variations with particle size). The SF(E) is
      the ratio of the effective dose given under a uniform or linearly changing
      radioactivity distribution across the particle size interval to that given for a
      mono-sized radioactivity distribution for the same impactor stage. The latter
      approach can initially be used (which requires less computational effort)
      followed by a rescaling of the effective dose either upward or downward by the
      SF(E) value. In this earlier study, the LUDEP code was employed which utilizes
      the ICRP 66 human respiratory tract model along the radionuclide biokinetic
      models given in ICRP Publication 30. In the present study, inhalation dose
      coefficients and effective dose scaling factors were reexamined for several
      radionuclides of the (238)U series using the IMBA program, which employs more
      recent and physiologically realistic biokinetic models published by the ICRP. An
      update of the effective dose scaling factors is thus the primary focus of this
      study rather than an extensive inter-comparison of the IMBA and LUDEP codes.
      Inhalation dose coefficients calculated by the two programs differ by up to a
      factor of 5 for Type F (238)U and (234)U, but are within only 2% of each other
      for Type S radionuclides. The ICRP 69 biokinetic model of uranium predicts
      retention in bone and kidneys that is slightly higher than predicted in ICRP
      Publication 30, but is significantly higher in the liver and other soft tissues
      by up to 1 or 2 orders of magnitude. Nevertheless, effective dose scaling factors
      generated using the IMBA program are nearly identical to those calculated by the
      LUDEP program as their magnitude is primarily dictated by the dependence of
      particle deposition and lung clearance with particle size, and less by the
      systemic biodistribution of the radionuclide following absorption to blood. For
      both codes, greater than 10% re-scaling of the effective dose is required for
      third-stage (4.5 to 12 microm) and filter-stage (0.03 to 0.35 microm) particles
      in the approximation of uniform or linearly decreasing radioactivity
      distributions per particle stage. For linearly increasing distributions, greater
      than 10% corrections in the effective dose are found irregularly across impactor
      stage, radionuclide, and solubility class, especially for rather steep (1:5)
      impactor stage activity ratios.

PMID- 16966877
TI  - Comparison of natural background dose rates for residents of the Amargosa Valley,
      NV, to those in Leadville, CO, and the states of Colorado and Nevada.
AB  - In the latter half of 2005, the U.S. Environmental Protection Agency (U.S. EPA)
      published a Proposed Rule (40 CFR Part 197) for establishing a dose rate standard
      for limiting radionuclide releases from the proposed Yucca Mountain high-level
      radioactive waste repository during the time period from 10 to 10 years after
      closure. The proposed standard was based on the difference in the estimated dose
      rate from natural background in the Amargosa Valley and the "average annual
      background radiation" for the State of Colorado. As defined by the U.S. EPA,
      "natural background radiation consists of external exposures from cosmic and
      terrestrial sources, and internal exposures from indoor exposures to naturally
      occurring radon." On the basis of its assessments, the U.S. EPA estimated that
      the difference in the dose rate in the two identified areas was 3.5 mSv y. The
      purpose of this paper is to provide an independent evaluation and review of this
      estimate. One of the first observations was that, because site-specific dose rate
      measurements for the Amargosa Valley "were not available," the dose rates for
      various sources of natural background in that area, used by the U.S. EPA in its
      assessment, were based on modifications of the average values for the State of
      Nevada. A second observation was that the conversion coefficient applied in
      estimating the dose rates due to exposures to indoor radon and its decay products
      was a factor of >2 higher than the currently internationally accepted value.
      Further review revealed that site-specific data for many natural background
      sources in the Amargosa Valley were available. One particularly important
      observation was that about 91% of the residents of that area live in mobile homes
      which, due to their construction and design, have indoor radon concentrations
      comparable to, or less than, those outdoors. For that reason, alone, the U.S. EPA
      estimate of the average dose rate for residents of the Amargosa Valley, due to
      exposures to indoor radon, was not valid. For purposes of the comparisons in this
      paper, site-specific dose rates were estimated for all major natural background
      sources of exposure to residents of the Amargosa Valley, and those in Leadville,
      CO. The latter community was selected for comparison because of its altitude
      (3,200 m) and accompanying relatively high cosmic radiation dose rate, and the
      fact the size of its population is comparable to that of the Amargosa Valley.
      Another reason for this selection was that a comparison of the average natural
      background dose rate in the Amargosa Valley to that for the State of Colorado is
      not suitable because it fails to consider those locations within the State that
      have dose rates that are higher than the average. Nonetheless, for completeness,
      and to provide a number that could be compared to the U.S. EPA estimated
      difference, similar comparisons of the estimated dose rate in the Amargosa Valley
      to those for average residents of the States of Colorado and Nevada were included
      in the assessments that follow. The outcome showed that the estimated dose rates
      in Leadville, the State of Colorado, and the State of Nevada, were higher than
      those in the Amargosa Valley by 3.94 +/- 1.09, 2.54 +/- 2.18, and 0.95 +/- 0.82
      mSv y, respectively. Associated uncertainties were highest for the estimated dose
      rates due to exposures to radon and its decay products. Had the systematic errors
      in the radon dose conversion coefficient and the random distribution in radon
      concentrations been included, the overall uncertainty in the total dose rate
      estimates could have been as high as 150%.

PMID- 16966878
TI  - A laboratory intercomparison of radon in water measurements in Maine.
AB  - Naturally occurring radon exists in ground water and drinking water supplies.
      Many water testing laboratories provide measurements of radon in water for the
      public. No known national intercomparison program exists to verify the accuracy
      of the laboratories measuring radon in water in Maine or the Northeast. In
      recognition of this situation, the State of Maine Radiation Control Program
      sanctioned an intercomparison study for laboratories registered in Maine to
      measure radon in water. The University of Maine supplied each laboratory with
      water samples of various radon concentrations, served as the reference
      laboratory, and analyzed the results. Of the nine participating laboratories,
      eight use the liquid scintillation method while the ninth uses the E-PERM method
      to measure radon in water. Presented here are the results of this intercomparison
      study with a tabulation of the materials and methods used by the laboratories.
      The results from five of the nine testing laboratories showed significant
      discrepancies with those of the reference laboratory, typically due to low
      measurements.

PMID- 16966879
TI  - Doppler broadening effect on low-energy photon dose calculations using MCNP5 and
      PENELOPE.
AB  - Recent releases of the MCNP5 and PENELOPE Monte Carlo codes include the transport
      algorithm and momentum profiles that are necessary for accounting for Doppler
      broadening in Compton scattering processes. Such improvements might be
      particularly important in low-energy photon dose calculations. MCPLIB04 and
      PENDBASE (PENELOPE photon dataset) are based on the EPDL97 library with Compton
      momentum profiles, while MCPLIB03 and MCPLIB02 are based on the 1970's old
      library, with MCPLIB03 including the Compton momentum profiles. To isolate the
      dosimetric effects of Doppler broadening by the transport algorithm and Compton
      momentum profiles, we varied the choice of the above photon databases, in the
      same simulation geometry, using either version of MCNP5 or MCNP4 (no Doppler
      algorithm). We computed dose rate constants and dose distributions for r = 0.2-10
      cm from a point source in a 50-cm-diameter sphere of water. Nine discrete
      energies for primary photon sources were chosen in the range of 10-150 keV. The
      results from both versions of MCNP with MCPLIB04 agreed with those of PENELOPE
      within statistical uncertainties (+/-1%) over the entire ranges of energies and
      radial distances investigated. MCNP5 with either MCPLIB03 or MCPLIB02 yielded
      almost identical data within statistical uncertainties (+/-1%) over the entire
      ranges of energies and radial distances investigated. This implies that in spite
      of the spectral broadening of scattered photons due to the orbital electron
      motion, the dosimetric effect of Doppler broadening for Compton interactions in
      water appears to be insignificant in the energy range investigated. The spectral
      dose analysis with and without the Doppler broadening supported this conclusion.

PMID- 16966880
TI  - Sensitivity of portable personnel portal monitors: potential problems when
      dealing with contaminated persons.
AB  - Health physicists are usually concerned with small amounts of radioactivity and
      strive to develop techniques to measure them; however, following a terrorist
      attack involving radioactive materials the converse might be the case, and
      exposed persons may be heavily contaminated. The Human Monitoring Laboratory
      (HML) has field tested its Portable Personnel Portal (P3) monitors using sources
      up to 1,700 MBq (47 mCi) to determine the alarm distance as a function of
      activity. The results show that the P3 monitors are highly sensitive, so much so
      that siting will be a problem for multiple units if multiple alarms are to be
      avoided. Building materials will shield the monitors allowing units to be placed
      closer together than in the open where there is no shielding, but windows and
      doors reduce shielding and complicate the siting of multiple units. In either
      situation, careful prior thought should be given to siting the monitors and the
      logistics of crowd control techniques.

PMID- 16966881
TI  - The EPRI EDE calculator--a software package for assessing effective dose
      equivalent from hot particles on the skin.
AB  - Whole body exposure from photon-emitting hot particles is receiving new attention
      because of changes in skin dose regulations. A recent study calculated and
      tabulated effective dose equivalent (EDE) and effective dose (ED) for photon
      energies between 0.1 MeV and 2 MeV for point sources at 74 locations on the skin.
      This technical note describes a software package called the EPRI EDE Calculator
      that allows a user to input exposure data and to calculate the EDE and ED
      automatically.

PMID- 16966882
TI  - Reconstruction of external dose from beta radiation sources of nuclear weapon
      origin.
AB  - In response to requests from the Department of Veterans Affairs, a methodology
      was developed to assess the external dose accrued by personnel in the vicinity of
      beta radiation sources of nuclear weapon origin. This methodology has been
      applied in support of the Nuclear Test Personnel Review (NTPR) Program
      implemented by the Department of Defense. As required by the Code of Federal
      Regulations (Title 32, Part 218 and Title 38, Part 3.311), the NTPR Program must
      evaluate radiological hazards from nuclear testing activities that include alpha
      particle, beta particle, neutron, and photon emissions from radionuclides. Prior
      to the development of this methodology, only photon and neutron radiations were
      explicitly quantified for external dose assessments in this program. Alpha
      radiation of external origin presents no risk for biological effects due to
      external dose potential to skin tissue because of the particle's very limited
      range. However, beta particles are sufficiently penetrating to have such
      potential. Methods are provided to quantify ionizing radiation doses to the skin
      and lens of the eye from beta radiation sources of nuclear weapon origin located
      external to the body. This formulation allows the estimation of beta dose from a
      film badge (gamma) dose or from an equivalent reconstructed gamma dose.

PMID- 16966883
TI  - Errors and blunders in the estimation of radiation exposure for the uranium
      miners of WISMUT in Germany.

PMID- 16966885
TI  - Dosimetry for members of the extended Techa River cohort.

PMID- 16966886
TI  - Understanding the toxicity of buried radioactive waste.

PMID- 16966890
TI  - Beyond the hex.

PMID- 16966891
TI  - Endodontics versus implants.

PMID- 16966892
TI  - The critical role of the implant treatment coordinator.
AB  - Acting as a liaison, the ITC helps both the surgical and restorative practices
      provide optimal patient care, as well as eliminate miscommunication and
      bottlenecks. An ITC promotes increased implant production by allowing the surgeon
      to spend more time performing surgery and less time dealing with administrative
      work.

PMID- 16966893
TI  - Dental endosseous implants in patients on bisphosphonate therapy.
AB  - About a decade ago, bisphosphonates were introduced as an alternative to hormone
      replacement therapies for osteoporosis and to treat osteolytic tumors. More
      recently, it has became evident that the bisphosphonates used intravenously such
      as pamidronate (Aredia; Novartis Pharmaceuticals Corp., East Hanover, NJ) and
      zoledronate (Zometa; Novartis Pharmaceuticals Corp.), in particular, could lead
      to painful refractory bone exposure (sometimes termed osteochemonecrosis or
      osteonecrosis) in the jaws. Patients with osteonecrosis of the jaws usually
      present after dental treatment with oral signs and symptoms of painful, exposed,
      and necrotic bone, primarily of the mandible and, to a lesser extent, the
      maxilla. Although the precipitating event that produces this complication may be
      spontaneous, there is little doubt that oral surgery and endosseous implants can
      be responsible. Exodontia is the main precipitant. The present postulated
      mechanism of osteonecrosis of the jaws is that prolonged use of bisphosphonates
      may suppress bone turnover to the point that the repair function of physiologic
      microdamage of bone is abolished. Such a mechanism could presumably interfere
      with the healing process after implant placement. Although, to our knowledge,
      there is no evidence that bone disorders are a contraindication to implants,
      there is evidence that bisphosphonate therapy is a contraindication. Where
      possible, extractions should be avoided, and it is best to avoid all elective
      oral surgery in patients on bisphosphonates, including endosseous implant
      placement, or the treatment should be performed well before commencing
      bisphosphonates. If surgery is essential on a patient taking bisphosphonate
      therapy, the patient must be counseled about the risks.

PMID- 16966894
TI  - Vertical bone augmentation: where are we now?
AB  - As the prevalence of implants has increased, so has the challenge to augment the
      remaining osseous structure to house those implants. The biggest surgical
      challenge clinically is to augment lost bone vertically. The purpose of this
      article is to review currently available techniques for achieving greater
      vertical dimension before implant placement. A literature search was conducted
      using MEDLINE to find all articles published between 1970 and 2004 regarding
      vertical bone augmentation. Following the literature search, all articles were
      reviewed and summarized in this review article of vertical bone augmentation. The
      results of the research showed that guided-bone regeneration, monocortical onlay
      grafting, and distraction osteogenesis have the potential to be applied to
      augment deficient areas vertically. The expectations of dimensional gain and bone
      quality are unique to each technique, as well as the potential complications.
      Distraction osteogenesis has had the greatest potential for vertical gain, while
      guided-bone regeneration and monocortical onlay grafting achieve similar results.
      The choice of procedure is to be based upon the patient's existing anatomy,
      degree of vertical deficiency, and willingness to participate in treatment.

PMID- 16966895
TI  - Bone marrow aspiration: technique, grafts, and reports.
AB  - This article describes a technique for obtaining adult stem cells from bone
      marrow aspirate. Case reports show how this procedure might replace the gold
      standard for bone grafts with the platinum standard of obtaining stem cells. The
      bone marrow aspirate and transplantation of adult stem cells within the
      resorbable) matrix and under the influence of soluble regulators have the
      potential for introducing the platinum standard for bone grafts. There are
      several advantages to using bone marrow aspirate. The technique is simple, a
      second surgical site is not needed, there is minimal postoperative morbidity, and
      adult stem cells populate the graft site with osteoblasts.

PMID- 16966896
TI  - Plastic temporary abutments with provisional restorations in immediate loading
      procedures: a clinical report.
AB  - A provisional restoration in combination with an implant-retained restoration
      provides many of the same benefits as nonimplant-retained fixed restorations.
      Provisional restorations serve as a diagnostic tool to confirm esthetics,
      contours, accessibility for oral hygiene, and can be used to duplicate the
      definitive restoration. A provisional restoration allows for communication
      between the patient, dentist, and technician. The soft tissue around the implants
      can heal according to the contours of the provisional restoration. However,
      implant-retained treatment can require an extended period of osseointegration,
      and provisional treatment can be a challenge if a removable prosthesis is
      provided because adjustments of the denture may become necessary during healing.
      This article presents a case report that describes the simultaneous placement of
      implants with the connection of fixed provisional restorations to prefabricated
      plastic provisional abutments.

PMID- 16966897
TI  - Prosthetic rehabilitation of a bone defect with a teeth-implant supported,
      removable partial denture.
AB  - The use of teeth-implant, mucosa-supported removable dentures for rehabilitation
      of partially edentulous patients involves highly complex biomechanical aspects.
      This type of prosthesis associates 3 kinds of support that react differently to
      the functional and parafunctional forces developed in the oral cavity. Although
      the construction of removable partial dentures may seem paradoxical when
      osseointegrated implants are placed, in some cases, this option is an excellent
      alternative to solve difficulties related to the anatomic, biologic, psychomotor,
      and financial conditions of the patient. This article reports on a case in which
      a teeth-implant, mucosa-supported removable partial denture was the option of
      choice for a patient with financial and anatomic limitations, having a large
      structural loss of the residual alveolar ridge caused by trauma by a gunshot
      injury at the mandible. The 5-year follow-up did not reveal any type of
      biomechanical or functional problem.

PMID- 16966898
TI  - Dentin dysplasia type I treated with onlay bone grafting, sinus augmentation, and
      osseointegrated implants.
AB  - Dentin dysplasia is a defect of dentin development that was classified by Shields
      as type I and type II. The teeth in dentin dysplasia type I are characterized by
      normal enamel and abnormal dentin in the crown and root. For that reason, this
      disorder is characterized by dental caries, early exfoliation of the teeth and,
      consequently, maxillomandibular bony atrophy. In this report, we present a case
      of a young girl affected by dentin dysplasia type I, treated with a combination
      of onlay bone grafting and a sinus lift technique to accomplish implant
      placement. This case showed that onlay autogenous grafting and a sinus lift
      technique are well-tested methods of bony augmentation and can be useful in
      patients with congenital dentin defects, such as dentin dysplasia.

PMID- 16966899
TI  - Finite element analysis of different bone substitutes in the bone defects around
      dental implants.
AB  - PURPOSE: To evaluate the distribution of stress and strain for the evaluation of
      implant and graft stability at each stage before stabilization of the graft is
      achieved after implantation was performed. MATERIALS AND METHODS: Dembone
      (Pacific Coast Tissue Bank, Los Angeles, CA), Bio-Oss (Geistlich Pharma,
      Wolhusen, Switzerland), particulate dentin, and plaster of Paris were used to
      fill bone defects. The distribution of stress was compared in the mandible and
      maxilla, between vertical load and load applied at 30 degrees angle, and
      according to time, with 3 different graft materials. RESULTS: Stress occurred
      more when it was applied at an angle, rather than applied vertically. Stress was
      relatively high immediately after implantation, and particulate dentin-plaster of
      Paris showed larger mechanical properties and lower stress distribution overall.
      The largest stress distribution was shown when stress was applied at an angle
      when demineralized freeze-dried bone was used. The pattern of stress distribution
      was different according to differences in the mechanical properties of implants.
      CONCLUSION: Caution is needed not to apply stress at an angle immediately after
      implantation. Differences of stress were reduced with time as the implant became
      stabilized.

PMID- 16966900
TI  - Heterotopic bone formation around sintered porous-surfaced Ti-6Al-4V implants
      coated with native bone morphogenetic proteins.
AB  - PURPOSE: Coating endosseous dental implants with growth factors such as bone
      morphogenetic proteins (BMPs) may be one way to accelerate and/or enhance the
      quality of osseointegration. The purpose of this study was to investigate in the
      murine muscle pouch model whether sintered porous-surfaced titanium alloy
      implants coated with BMPs would lead to heterotopic bone formation around and
      within the implant surface geometry. MATERIALS: Porous-surfaced dental implants
      were coated with partially purified native human BMPs, with or without a carrier
      of Poloxamer 407 (BASF Corp., Parsippany, NJ), placed in gelatin capsules and
      implanted into the hindquarter muscles of mice. Mice were euthanized after 28
      days. Sections of retrieved specimens were subsequently prepared for morphometric
      analysis of bone formation using backscatter electron microscopic images.
      RESULTS: Human BMPs, either with or without the carrier of Poloxamer 407, led to
      bone formation within and outside of the sintered porous implant surface. When
      the sintered implant surface region was subdivided into inner and outer halves,
      similar levels of bone ingrowth and contact were seen in the 2 halves. Evidence
      of bone formation to the depth of the solid implant core (i.e., the deepest level
      possible) also was seen. DISCUSSION AND CONCLUSIONS: Sintered porous-surfaced
      dental implants can be used as substrate for partially purified BMPs in the
      murine muscle pouch model. With the addition of these osteoinductive factors, the
      porous implant surface supported bone formation within the surface porosity
      provided, in some instances, all the way to the solid implant core. The addition
      of growth factors to a sintered porous surface may be an efficient method for
      altering locally the healing sequence and quality of bone associated with
      osseointegration of bone-interfacing implants.

PMID- 16966901
TI  - Increasing the width of keratinized mucosa around endosseous implant using
      acellular dermal matrix allograft.
AB  - OBJECTIVES: To: (1) investigate the clinical efficacy of acellular dermal matrix
      allograft to achieve increased peri-implant keratinized mucosa around implants,
      and (2) evaluate the effect as to whether the increase of keratinized mucosa has
      a positive effect on oral hygiene. MATERIALS AND METHODS: There were 10 male
      patients, ranging from 43 to 53 years of age, with attached gingiva < or = 2 mm
      on the buccal aspect included in this study. Acellular dermal matrix allograft
      was used to increase the keratinized mucosa on the buccal side. RESULTS: The
      change of peri-implant pocket depth showed statistical differences among 3
      measurements. The modified plaque index at 3 and 6 months showed statistical
      differences compared with the baseline measurements. The modified gingival index
      did not show any significant differences among all measurements. The width of
      peri-implant keratinized mucosa increased from a mean of 0.8 +/- 0.6 to 3.2 +/-
      0.9 mm at 3 months and 2.2 +/- 0.6 mm at 6 months. CONCLUSIONS: It is concluded
      that the acellular dermal matrix allograft could be applied as a grafting
      material to increase the width of peri-implant keratinized mucosa. Its procedure
      appears to have some benefits for oral hygiene. Further randomized controlled
      trials over long periods of time are necessary to establish whether this
      procedure offers long-tem benefits to patients.

PMID- 16966902
TI  - Reconstruction of a mandibular critical-sized defect using iliac graft in rats.
AB  - OBJECTIVE: To evaluate, histologically and by optical densitometry of
      radiographs, the healing of a critical-sized defect in the rat mandible filled
      with iliac graft. MATERIALS: The study was conducted on 25 adult Wistar rats.
      With the rats under general anesthesia, a bicortical critical-sized osseous
      defect was created in the right mandibular ramus and filled with autogenous iliac
      crest graft. The animals were divided into 5 groups, with 5 rats in each. They
      were sacrificed after 1, 7, and 14 days, and 1 and 3 months. The mandibles were
      removed, fixed in formalin, and radiographed. The right hemi-mandibles were
      decalcified, and sections were cut and stained with hematoxylin and eosin.
      RESULTS: Initially, an acute inflammatory process was noted along the graft that
      was tightly fitted to the defect. Subsequently, intense bone neoformation from
      external corticals and in the inner spaces of the graft was observed, while
      medullar spaces were occupied by granulation tissue and osteoblasts. There was
      remodelation of the receptor site, with a decrease in the graft volume and
      medullary space, as well as cancellous bone replaced by compact bone. Later, the
      receptor site was similar to the normal mandible, and only devitalized remnants
      of corticals of the graft were found. Optical densitometry of radiographs
      revealed statistically significant differences between experimental and control
      sites. CONCLUSIONS: This experimental model is valuable in the study of bone
      healing. The study showed that autogenous iliac graft promoted healing of the
      critical-sized defect of the mandible with complete bony remodeling.

PMID- 16966903
TI  - Measuring mobility of 2 dental implant fixtures of different configurations: an
      in vitro study.
AB  - OBJECTIVES: To our knowledge, it has not as yet been determined if mini-dental
      implants can be used as a long-term treatment method compared to endosseous
      standard root-form dental implant fixtures. This in vitro study investigates the
      stability of 2 different implants, 1 mini-dental implant and 1 endosseous
      standard root form dental implant, under lateral forces. METHODS: There were 2
      different screw-type dental implants with the O-ring/ball attachment prosthetic
      heads used. A mini-dental implant (Sendax MDI MAX; IMTEC, Corp., Ardmore, OK) 13
      mm in length and 2.2 mm in diameter, and root form implant (Branemark; Nobel
      Biocare AB, Goteborg, Sweden) 13 mm in length and 4 mm in diameter. These
      implants were then embedded into a matrix mixture of pumice, two-fifths BaSO4
      powder and one-fifth plaster. Parallel periapical radiographs were taken pretest
      and after lateral forces were applied. The implants were vibrated using electric
      toothbrushes. They were attached to O-rings on the implants. Periapical
      radiographs were secured periodically every 5 minutes. The first discrepancy was
      observed at the 35th minute. Mobility and discrepancy values were recorded at the
      instances of 35th, 60th, 90th, and 120th minutes. Stability was measured and
      recorded using a manual stress and tension gauge. Radiographic discrepancy values
      were measured using a stereomicroscope. RESULTS: The Branemark implant showed
      less mobility and discrepancy values than the mini-dental implant. The
      discrepancies were observed mostly at the cervical region of the 2 implants.
      CONCLUSIONS: According to the experimental results of this study, the Branemark
      implant was more stable than the mini-dental implant at the end of 2 minutes.

PMID- 16966904
TI  - Bacterial plaque colonization around dental implant surfaces.
AB  - PURPOSE: To examine the distribution of bacteria into the internal and external
      surfaces of failed implants using histologic analysis. MATERIALS AND METHODS:
      There were 10 failed pure titanium and 5 failed hydroxyapatite-coated titanium
      implants consecutively removed various years after their placement. Criteria for
      fixture removal were peri-implant radiolucency and clinical mobility. The mobile
      fixtures were retrieved with the patients under local anesthesia. Fixtures were
      removed maintaining the abutments with the aim to observe the bacterial
      infiltration at the level of abutment/implant interface and on the implant
      surface. RESULTS: A thin radiolucent space was always present around all the
      failed implants. The abutments screws were tightly secured in all clinical cases.
      The bacterial cells were composed of cocci and filaments, which were adherent to
      the implant surface with an orientation perpendicular to the long axis of the
      implant. All the specimens included in this study showed bacteria at the level of
      implant/abutment interface. CONCLUSIONS: Histologic analysis at the level of
      abutment/implant interface in 2-stage implants identified heavy bacterial
      colonization. These findings appear to support those studies showing bacteria
      penetration at the level of the micro-gap, which can legitimate the hypothesis
      that the micro-gap at the bone level could present a risk for bone loss caused by
      bacterial colonization.

PMID- 16966905
TI  - Histologic evaluation of 3 retrieved immediately loaded implants after a 4-month
      period.
AB  - OBJECTIVE: To perform a histologic and histomorphometric analysis of the peri
      implant tissue reactions and bone-titanium interface in 3 immediately loaded
      (provisional loaded) titanium implants retrieved from a man after a loading
      period of 4 months. MATERIALS & METHODS: A 35-year-old patient with a maxillary
      partial edentulism did not want to wear a provisional removable prosthesis during
      the healing period. It was decided to insert 3 definitive implants and use 3
      provisional implants for the transitional period. The provisional implants were
      loaded the same day with a resin prosthesis in occlusal contact. During the
      second surgical phase, after 4 months, the provisional prosthesis was removed,
      and the provisional implants were retrieved with a trephine bur. Before
      retrieval, all implants appeared to be clinically osseointegrated. The specimens
      were processed for observation under light microscopy. RESULTS: At low
      magnification, it was possible to observe that bone trabeculae were present
      around the implant. Areas of bone remodeling and haversian systems were present
      near the implant surface. Under polarized-light microscopy, it was possible to
      observe that in the coronal aspect of the thread, the lamellar bone showed
      lamellae that tended to run parallel to the implant surface, while in the
      inferior aspect of the thread, the bone lamellae ran perpendicular to the implant
      surface. CONCLUSIONS: Histologic data pertaining to these 3 immediately loaded
      implants, and retrieved after a 4-month loading period, show that immediate
      loading did not produce untoward effects on peri-implant bone healing.

PMID- 16966906
TI  - Benefits of an implant platform modification technique to reduce crestal bone
      resorption.
AB  - PURPOSE: The alveolar bone resorption that occurs around a 2-piece implant
      following abutment attachment is a well-documented observation. Several
      investigators propose that crestal bone loss is a response to the invasion of the
      biologic width by secondary bacterial colonization and micromovements at the
      implant-abutment interface. This study proposes the creation of a difference
      between the diameter of the implant platform and diameter of the abutment
      (implant platform modification), shifting the implant-abutment interface medially
      to minimize invasion of the biologic width. MATERIAL AND METHODS: We present a
      series of 30 control cases and 30 study cases using the platform-modification
      technique. Interproximal bone resorption on the medial and distal of each implant
      was assessed using digital radiography at 1, 4, and 6 months after abutment
      attachment. RESULTS: The mean value of bone resorption observed in the mesial
      measurement for the control group was 2.53 mm, whereas for those patients
      included in the study group, it was 0.76 mm. The mean value of bone resorption
      observed in the distal measurement for patients in the control group was 2.56 mm,
      whereas for those included in the study group, it was 0.77 mm. CONCLUSIONS: All
      patients in the study group had a significant reduction of bone loss in
      comparison to the control group (P < 0.0005).

PMID- 16966907
TI  - Knowing your risk factors for coronary heart disease improves adherence to advice
      on lifestyle changes and medication.
AB  - Implementation of guidelines for coronary heart disease prevention is less
      optimal in clinical practice. The aim of this study was to investigate if
      specific knowledge (patients' knowledge about their own coronary heart disease
      risk factors) would correlate to their adherence as measured by self-reported
      lifestyle changes, reaching defined treatment goals and adhering to treatment
      with prescribed drugs. The consecutive medical records of 509 men and women
      younger than 71 years, hospitalized for a cardiac event, were screened. Of these,
      392 patients came for an interview and were subjected to a clinical examination.
      All patients received a questionnaire regarding their specific knowledge of risk
      factors and their adherence to lifestyle changes, which was completed by 347
      patients. In addition, data were collected and analyzed on how their treatment
      goals were attained in 8 domains and their adherence to drug treatment. There
      were significant correlations between specific knowledge and self-reported
      lifestyle changes, the ability to reach treatment goals in all 8 domains, and
      adherence to prescribed drugs. Patients with coronary heart disease will benefit
      from increased specific knowledge of risk factors to adhere with lifestyle
      changes and prescribed medication after a cardiac event.

PMID- 16966909
TI  - Progress in prevention: secondary prevention of primary importance.

PMID- 16966910
TI  - Missed targets: gender differences in the identification and management of
      dyslipidemia.
AB  - Gender differences in the treatment of heart disease have a significant impact on
      the outcomes and mortality for women. From screening and detection, through
      treatment and intervention, women are less likely than men to receive guideline
      based care. Risk factor modification, including lipid management, is critical to
      all levels of prevention. This article discusses gender differences in the
      detection and management of dyslipidemia. By identifying the suboptimal
      recognition and treatment of lipid abnormalities in women, healthcare
      professionals can revise their practice patterns in an effort to improve the
      outcomes for women with cardiovascular disease.

PMID- 16966911
TI  - The relationship of blood pressure and cortisol reactivity to family history of
      hypertension of African American adolescents.
AB  - Ethnicity and family history of hypertension (FHH) have been associated with the
      development of hypertension. Blood pressure and cortisol reactivity during
      physiologic stress are hypothesized to function as biologic markers for
      hypertension. The purpose of this study was to explore the relationship of blood
      pressure and cortisol reactivity physiologic to FHH in a selected sample of
      African American adolescents. METHODS: Demographic data and physiologic
      measurements were obtained from 48 African American adolescents (14-17 years).
      Reactivity was induced by a cold pressor test of hand immersion in cold water.
      chi, t tests, and multivariate repeated-measures analysis were used to determine
      relationships. RESULTS: Thirty-one (65%) subjects reported an FHH. Thirty (63%)
      subjects demonstrated cardiovascular reactivity. Although the mean systolic blood
      pressure was 4 mm Hg higher, t tests indicated no significance between group in
      systolic blood pressure (P = .32), diastolic pressure (P = .73), and cortisol (P
      =.81). Blood pressure reactivity of the FHH group was significantly different
      than the no family history group (P = .0338). Cortisol levels for the total group
      were markedly elevated (19 nmol/dL) and there was no significant difference in
      reactivity. CONCLUSION: African American adolescents with FHH demonstrate
      increased blood pressure reactivity. Cortisol levels were elevated for all
      participants. This study adds support to the association of blood pressure
      reactivity, a biologic marker of HTN and FHH.

PMID- 16966912
TI  - Cultural factors associated with antihypertensive medication adherence in Chinese
      immigrants.
AB  - BACKGROUND: Little is known about hypertension control and cultural factors
      related to medication adherence in Chinese immigrants. OBJECTIVE: : The purpose
      of this study was to characterize Chinese immigrants with hypertension and to
      examine what cultural factors are associated with medication adherence. METHODS:
      A cross-sectional design was used. Data were gathered from a convenience sample
      of 200 subjects recruited in an Asian outpatient clinic in the San Francisco Bay
      Area using self-report questionnaires and blood pressure measurements.
      Participants were Chinese immigrants 18 years old and older, taking
      antihypertensive medications, and able to speak Mandarin. RESULTS: The mean age
      was 71 (+/-10) years. Half were men (50%). Most were married (70%), and reported
      an annual family income of <20,000 dollars (71%) and an average length of stay in
      the United States of 13 (+/-7) years. Medication adherence was reported by 75%,
      although only 51% had controlled hypertension. Four of 8 cultural factors were
      statistically significant predictors for medication nonadherence: lower perceived
      susceptibility [OR = 3.77 (95% CI 1.19, 12.01)]; higher perceived benefit of
      Chinese herbs [OR = 2.21 (95% CI 1.02, 4.81)]; lower perceived benefit of Western
      medications for hypertension [OR = 2.78 (95% CI 1.13, 6.84)]; and longer length
      of stay in the United States [OR = 2.48 (95% CI 1.12, 5.50)]. CONCLUSIONS: Four
      cultural factors were identified as significant predictors of medication
      nonadherence in this sample. These findings can guide culturally appropriate
      nursing interventions for hypertension management in Chinese immigrants.

PMID- 16966913
TI  - Self-rated competency and education/programming needs for Care of the Older Adult
      with Cardiovascular Disease: a survey of the members of the Council of
      Cardiovascular Nursing.
AB  - An online survey, Care of the Older Adult with Cardiovascular Disease (COA-CVD),
      was used to describe self-rated competency in the care of the aging adult with
      cardiovascular disease and subsequently determine the future education and
      programming needs of the Council of Cardiovascular Nursing. Respondents indicated
      that developing relationships, patient teaching, and assessment were areas where
      they felt most competent. The areas of highest priority for future programming
      included assessment of the older adult, diagnosis of health status, deriving a
      plan of care, implementing a treatment plan, patient teaching, and ensuring
      quality care. Most stated that content relative to the care of the older adult
      should be available at the annual meeting, Scientific Sessions of the American
      Heart Association, followed by self-study modules (65%), local and regional
      conferences (64%), and stand-alone national conferences (53%). The conclusions
      are that the Council of Cardiovascular Nursing and its membership need to address
      the importance of care of aging adults with cardiovascular disease and stroke in
      future programming. Although the Scientific Sessions of the American Heart
      Association is an appropriate venue, efforts can be directed toward developing
      self-study modules and local and regional conferences. As always, there is a need
      to work collaboratively with the other councils of the American Heart Association
      and other nursing organizations who view the care of the older adult as a high
      priority.

PMID- 16966915
TI  - Persistence of coronary risk factor status in participants 12 to 18 months after
      percutaneous coronary intervention.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) is a widely performed
      revascularization technique for coronary heart disease; however, there is limited
      research investigating the risk factor status of patients 1 year after the
      procedure. OBJECTIVE: This cross-sectional study was conducted to investigate the
      self-reported risk factor status by patients who had undergone a PCI at a major
      teaching hospital in Sydney, Australia. SUBJECTS: : Two hundred seventy
      participants who underwent PCI between April 2003 and March 2004 and who met the
      inclusion criteria were followed up 1 year after the PCI. METHODS: After
      obtaining informed consent, a follow-up self-administered questionnaire was
      mailed to participants. Information was collected relating to the following
      coronary risk factors: smoking, and physical activity status, blood pressure and
      cholesterol levels, body mass index, depression, anxiety, and stress levels.
      RESULTS: Two hundred two participants (75%) returned a completed questionnaire.
      Approximately one third of participants had at least two modifiable risk factors.
      The most common cardiovascular risk factors identified were physical inactivity,
      increased body mass index, high blood pressure, and high cholesterol.
      Approximately half the women (46%) and a quarter of the men had at least two
      modifiable risk factors. Only a minority (11%) of the participants continued to
      smoke at 1-year follow up. Participating in physical activity for a total time of
      150 minutes or more per week was reported by only 42% of the participants.
      Depression and anxiety were present in 25% and stress in 17% of the participants.
      A third of the participants (n = 64) erroneously believed that they had no heart
      problems. CONCLUSIONS: The findings reveal inadequate management of modifiable
      risk factors among post-PCI participants 12 to 18 months after revascularization,
      which highlights a need for tailored secondary prevention interventions to
      address factors contributing to cardiovascular risk. The evidence obtained from
      this study will inform the development of an intervention to address
      cardiovascular risk factor modification.

PMID- 16966914
TI  - Racial disparities in outcomes following coronary artery bypass grafting.
AB  - More than 12 million people in the United States have coronary heart disease, the
      second leading cause of hospitalization in the United States. It is known that
      persons within racial minorities, specifically African Americans, have a higher
      prevalence of coronary heart disease, yet are much less likely to undergo
      invasive cardiac treatment interventions. An invasive intervention commonly used
      to treat coronary heart disease is coronary artery bypass grafting, with over
      140,000 operations performed annually in the United States. However, blacks are
      known to experience higher post-coronary artery bypass graft morbidity and
      mortality. The causes for racial disparities in post-coronary artery bypass graft
      outcomes are not well known but may include factors related to the individual,
      provider, system, and society/environment, either alone or in combination. The
      purpose of this article is to provide an overview of the literature regarding
      disparities in the health and healthcare of black patients with coronary heart
      disease with respect to CABG, and examine potential hypotheses for variant
      outcomes after surgery.

PMID- 16966916
TI  - Perceived effects on patients' health of participation in the atrial fibrillation
      follow-up investigation of rhythm management study.
AB  - BACKGROUND: Patients' views about participation in clinical trials have been
      explored using end-of-study questionnaires for various disease entities. However,
      little is known about why individuals with atrial fibrillation (AF) choose to
      participate in clinical trials or how they view their research experience.
      Understanding these perceptions should provide valuable information for future
      studies in developing methods to enhance enrollment, optimize adherence to
      therapies, and maximize patient retention. METHODS: The Atrial Fibrillation
      Follow-up Investigation of Rhythm Management (AFFIRM) Study was a randomized
      trial of rate-control versus rhythm-control for the management of AF. This
      descriptive ancillary study used a 7-item questionnaire comprising closed and
      open-ended items that explored: (1) perceptions of benefits from participation,
      (2) motivation for enrolling, and (3) satisfaction with research staff and
      operations. RESULTS: A total of 741/1,032 participants (72%) at 34 of 213
      participating AFFIRM sites responded, representing 18% of the 4,060 patients
      enrolled. The mean follow-up of these respondents was 3.8 +/- 1.1 years. Most
      respondents (91%) felt that they received enough information about AFFIRM before
      enrolling and that the results would benefit themselves (88%) and others (91%).
      Most respondents felt study participation improved awareness about AF (90%) and
      facilitated coordination of their healthcare (89%). Virtually all were satisfied
      with information received from AFFIRM personnel (96%), and most (98%) reported
      that they had received "good care." Responses were similar between randomization
      groups (rate-control or rhythm-control) and between those younger than 65 years
      and those 65 years or older. Participants in sinus rhythm at last follow-up were
      more likely to believe that their medical care in AFFIRM was better than what
      they would otherwise have received, and were more likely to perceive their
      treatment course as entailing fewer emergency room visits, hospitalizations, and
      doctor visits. Regularly scheduled appointments and ongoing availability of staff
      to answer questions appeared to increase participants' confidence and reduce
      anxiety. CONCLUSIONS: Patients enrolled in a long-term clinical trial for
      management of AF were overwhelmingly satisfied with participation.

PMID- 16966917
TI  - Enhancing care for cardiac resynchronization therapy patients: device diagnostics
      and clinical application.
AB  - Implantation of a cardiac resynchronization device in patients with heart failure
      does not attenuate the vigilant monitoring required by clinicians. Daily
      information about symptoms, quality of life, and weight are often part of routine
      care. Cardiac resynchronization devices also contain data on various heart
      failure parameters that can be obtained in or out of clinic. A number of cardiac
      resynchronization devices now have the ability to transmit such data to secure
      Internet sites, which can be accessed by clinicians. Incorporating these device
      data into daily practice can enhance current care. For instance, such data can
      confirm subjective patient reporting, help diagnose changes in the patient's
      condition, assist in deciding what changes to make in pharmacologic therapy, and
      assess the impact of device or pharmacologic therapy. Reviewing and utilizing
      device diagnostics may allow clinicians to intervene before a decompensation
      event and prevent a subsequent hospitalization. It is also likely that these
      device diagnostics can reduce the amount of time cardiovascular nurses spend on
      patient follow-up, thus enhancing efficiency in the clinical setting.

PMID- 16966918
TI  - Associations between depression, fatigue, and life orientation in myocardial
      infarction patients.
AB  - BACKGROUND: The possible preventive and treatment measures for post-myocardial
      infarction fatigue may rely on gaining insight into the psychosocial factors
      associated with fatigue. One such factor may be life orientation, that is, having
      an optimistic versus pessimistic view of life. Optimists expect things to turn
      out for the good, whereas pessimists generally expect that bad things will happen
      to them. OBJECTIVE: The aim of this study was to explore the relations among life
      orientation (optimism-pessimism), depression, and fatigue after a first-time
      myocardial infarction. METHODS: The sample included 98 patients in total, 33
      women and 65 men, who had suffered a first-time myocardial infarction 1 year
      before the testing. Linear and curvilinear regression analysis models were used
      to describe and explore the associations between the variables. RESULTS: A
      nonlinear relationship between postmyocardial fatigue and life orientation was
      found. The interpretation was that a pessimistic view of life could have more
      negative consequences for postmyocardial fatigue than an optimistic view of life
      could have positive consequences. The association between depression and fatigue
      was weak, supporting the notion that fatigue may be experienced by myocardial
      infarction patients without coexisting depression. CONCLUSION: Post-myocardial
      infarction fatigue must be investigated further and explicitly focused upon. One
      way to decrease postmyocardial fatigue could be to focus on steps that cause the
      most pessimistic individuals to feel less pessimistic.

PMID- 16966920
TI  - Measurement of anxiety for patients with cardiac disease: a critical review and
      analysis.

PMID- 16966923
TI  - Management of heart failure in older adults.
AB  - The incidence of heart failure in the United States is approaching 5 million
      patients with approximately 550,000 new cases identified each year. In addition,
      the prevalence of heart failure increases with age. Heart failure as a common
      chronic syndrome in the geriatric population challenges healthcare providers in
      the provision of patient care and improvement of patient outcomes. The purposes
      of this article are to (1) describe medication use and its associated challenges
      and (2) discuss hospitalization and outpatient management for older adults with
      heart failure with the goal of improving patient outcomes.

PMID- 16966924
TI  - Peripheral arterial disease in older adults: management of cardiovascular disease
      risk factors.
AB  - Patients with peripheral arterial disease experience significant functional
      limitations due to ischemic symptoms (claudication) and are at high risk for
      cardiovascular disease morbidity and mortality resulting from untreated
      cardiovascular disease risk factors and aggressive atherosclerosis. Peripheral
      arterial disease is commonly undiagnosed and cardiovascular disease risk factors
      are frequently untreated in this population. The increased risk associated with
      peripheral arterial disease necessitates greater emphasis on detection and
      management, not only to improve survival but to improve functional capacity and
      quality of life. This article briefly describes the detection and medical
      management with emphasis on lifestyle modification for elders with peripheral
      arterial disease.

PMID- 16966925
TI  - Depression, isolation, social support, and cardiovascular disease in older
      adults.
AB  - Research evidence related specifically to psychosocial issues in older adults
      with cardiovascular disease remains sparse; however, widespread recognition of
      the impact of the changing population demographic is spurring new research in
      this important area. National guidelines for cardiac rehabilitation and secondary
      prevention in several countries include recommendations related to psychosocial
      issues; authors are beginning to address the older cardiac patient in their
      recommendations. The purpose of this article is to highlight some key
      psychosocial factors that have been independently associated with coronary heart
      disease but to do so with a focus on the older adult in the secondary prevention
      setting. The selected psychosocial factors are social support, social isolation,
      and depression. Although evidence supports a relationship between psychosocial
      factors and coronary heart disease, the issue addressed in this article is
      whether such relationships hold true in the older adult and whether
      rehabilitation and secondary prevention interventions are targeted to address
      these factors. As much as possible, current recommendations (related to
      psychosocial issues) from worldwide Clinical Practice Guidelines are highlighted.
      Finally, any examination of psychosocial factors and coronary heart disease must
      consider the possibility of sex and/or gender differences. Therefore, a
      commentary on reported differences between men and women with respect to social
      support, social isolation, and depression is included.

PMID- 16966926
TI  - Stroke prevention and management in older adults.
AB  - Stroke is the third leading cause of death and a foremost cause of serious, long
      term disability in the United States. As cardiovascular and metabolic disease
      incidence rises with age, older people are more likely to experience strokes. Age
      is the single most important risk factor for stroke. For each successive 10 years
      after age 55, the stroke rate more than doubles in both men and women. However,
      stroke is not an inevitable consequence of aging. By identifying and modifying
      risk factors in older people, nurses can partner with other providers to reduce
      the incidence, morbidity, and mortality associated with stroke in older adults.
      Control of hypertension, resolution of dyslipidemia, management of diabetes
      mellitus, anticoagulation for atrial fibrillation, promotion of exercise and
      healthy diet, and cessation of cigarette smoking are of particular importance in
      older adults. Recognition of stroke symptoms, access to emergency evaluation and
      treatments, and participation in comprehensive rehabilitation may determine
      stroke outcomes in aging. This article presents stroke risk factors and primary
      and secondary prevention in the context of aging, with special considerations in
      the identification and management of acute stroke, recovery, and rehabilitation
      for older adults who survive stroke.

PMID- 16966927
TI  - Cardiovascular disease risk reduction in older adults.
AB  - Preventing cardiovascular events in older persons presents unique challenges to
      clinicians. Cardiovascular disease accounts for a large amount of disability and
      mortality in older persons. Older persons are often faced with unique and
      multiple challenges to health, including cognitive decline, social isolation,
      financial constraints, and physical disabilities. As more and more older persons
      are enrolled in studies that aim to better understand coronary heart disease and
      its prevention, new information is becoming available that allow clinicians to
      improve outcomes in the older adult. The most recent updates in the area of
      medical management, as well as updates of recommendations for lifestyle changes,
      including physical activity and dietary recommendations for older persons at
      risk, are presented in this article.

PMID- 16966931
TI  - A CR(I)MP in the optic nerve: recognition and implications of paraneoplastic
      optic neuropathy.

PMID- 16966930
TI  - Analysis of measures of functional and cognitive ability for aging adults with
      cardiac and vascular disease.
AB  - Baseline and follow-up assessments of functional and cognitive status are
      essential for aging patients who survive acute cardiac and vascular disease, as
      they are faced with new medications and implementing changes in lifestyle.
      Because declining functional and/or cognitive status will interfere with
      treatment regimens and taking prescribed medications, it is imperative that
      healthcare providers develop an understanding of approaches to functional and
      cognitive assessment that can be used with aging patients, selecting those most
      appropriate for the venue in which they practice and for their particular patient
      population.

PMID- 16966932
TI  - Small cell lung carcinoma presenting as collapsin response-mediating protein
      (CRMP) -5 paraneoplastic optic neuropathy.
AB  - A 77-year-old woman presenting with progressive visual loss in both eyes was
      found to have small cell lung cancer. Assay for collapsin response-mediating
      protein (CRMP) -5 was positive suggesting a paraneoplastic optic neuropathy
      (PON). During treatment of the small cell lung cancer, the patient died of
      pneumonia and autopsy disclosed neuropathologic abnormalities consistent with
      PON. This is only the second case of CRMP-5-confirmed PON to report
      neuropathologic findings.

PMID- 16966933
TI  - Unilateral midbrain infarction causing upward and downward gaze palsy.
AB  - We report on a 47-year-old-woman who developed sudden complete loss of vertical
      saccades, smooth pursuit, and vestibular eye movements bilaterally. MRI revealed
      a unilateral midbrain infarct involving the rostral interstitial nucleus of the
      medial longitudinal fasciculus (riMLF) and the interstitial nucleus of Cajal
      (INC) and spared the posterior commissure (PC). The lesion is presumed to have
      interrupted the pathways involved in vertical gaze just before they decussate,
      inducing an anatomically unilateral but functionally bilateral lesion. Previous
      reports of bidirectional vertical gaze palsy have shown lesions involving the PC
      or both riMLFs. This case is the first to show that a unilateral lesion of the
      riMLF and the INC that spares the PC may cause complete bidirectional vertical
      gaze palsy.

PMID- 16966934
TI  - A case of bilateral simultaneous sixth cranial nerve palsies secondary to
      diabetes mellitus.
AB  - Ocular motor cranial nerve palsy secondary to diabetes mellitus usually affects
      one cranial nerve at a time. We report a patient with simultaneous bilateral
      sixth nerve palsies attributed to diabetes. Although an extremely rare cause of
      this phenomenon, diabetes may be the explanation after other causes have been
      excluded.

PMID- 16966935
TI  - Homonymous hemianopia in stroke.
AB  - BACKGROUND: Previous reports have suggested that most cases of homonymous
      hemianopia (HH) are caused by occipital stroke. However, these reports have not
      always been supported by brain imaging. METHODS: We reviewed the medical records
      of all patients seen in our unit between 1989 and 2004 who had HH documented by
      formal perimetry or confrontation visual fields and had undergone brain imaging.
      HHs were divided into those caused by stroke and by non-stroke conditions. The
      clinical and visual field characteristics were compared in the two groups.
      RESULTS: Among 850 patients with 902 HHs, 629 (69.7%) resulted from stroke, of
      which 531 (84.4%) were from infarction and 98 (15.6%) from primary
      intraparenchymal hemorrhage. Non-stroke causes included head trauma (123), brain
      tumor (102), neurosurgical procedures (22), multiple sclerosis (13), and
      miscellaneous conditions (13). Occipital lesions most commonly resulted from
      stroke. The configuration of the HH did not predict where in the retrochiasmal
      visual pathway the responsible lesion lay. CONCLUSIONS: Ischemic stroke causes
      most HHs from lesions in the occipital lobe that generally do not produce other
      neurologic manifestations. The configuration of the HH does not predict the
      location of the lesion within the retrochiasmal visual pathway.

PMID- 16966936
TI  - Orbital apex syndrome from gnathostomiasis.
AB  - A 16-year-old Thai girl presented with acute unilateral visual loss, proptosis,
      and ophthalmoparesis. CT demonstrated thickening and enhancement of orbital
      tissues including the orbital apex. A history of consumption of raw fish,
      together with the findings of cutaneous migratory swelling and eosinophilia, made
      the diagnosis of gnathostomiasis likely. Her serum was positive for Gnathostoma
      spinigerum using an immunoblotting technique. Parasites removed from the skin
      lesions revealed the typical head bulbs with 4 circumferential rows of hooklets
      and fine cuticular spines on their surface. Treatment with an antihelminthic and
      systemic corticosteroids led to resolution of orbital inflammation but left a
      persistent optic neuropathy marked by nerve fiber bundle visual field loss with
      normal visual acuity. Gnathostomiasis should be suspected in patients with an
      orbital apex syndrome who live or travel in an endemic area, have eaten raw fish,
      and develop a migratory skin rash.

PMID- 16966937
TI  - Paroxysmal tonic downgaze in two healthy infants.
AB  - A 5-month-old boy and 7-month-old girl had episodes of downward eye deviation
      starting at age 5 months, lasting seconds to minutes, and associated with
      stiffening of the extremities in one case and grasping, flailing upper extremity
      movements and retroflexion of the head in the other. There were no other clinical
      abnormalities. Electroencephalography and MRI were normal. The episodes stopped
      after 6 to 12 weeks and there have been no sequelae. This idiopathic condition
      resembles paroxysmal tonic upgaze in infancy. Until further documentation clearly
      establishes that this phenomenon is benign, evaluation with MRI and
      electroencephalography is indicated.

PMID- 16966938
TI  - Optic neuropathy and sixth cranial nerve palsy caused by compression from a
      dolichoectatic basilar artery.
AB  - A 53-year-old man with progressive visual loss in the right eye and diplopia
      manifested dysfunction of the right optic nerve and the right sixth cranial
      nerve. MRI revealed a markedly enlarged and tortuous basilar artery, its proximal
      portion compressing the right sixth cranial nerve at the exit from the pons and
      its distal portion elevating and compressing the right optic nerve. This is the
      first report of optic neuropathy and sixth cranial nerve palsy caused by a
      dolichoectatic basilar artery.

PMID- 16966939
TI  - Regression of bilateral optic disc edema after discontinuation of amiodarone.
AB  - A 54-year-old non-obese woman treated with amiodarone reported blurred vision and
      had bilateral optic disc edema with relative preservation of visual function.
      Neurologic examination, brain imaging, and lumbar puncture opening pressures were
      normal, effectively ruling out increased intracranial pressure. Amiodarone was
      discontinued and the optic disc edema completely resolved over 15 months. In the
      absence of alternative explanations for the optic disc findings, amiodarone
      toxicity is suggested.

PMID- 16966940
TI  - Monocular temporal hemianopia with septo-optic dysplasia.
AB  - A 26-year-old woman displayed a monocular temporal hemianopic defect together
      with an ipsilateral afferent pupillary defect and bowtie optic nerve hypoplasia.
      MRI revealed a thin right optic nerve, an asymmetrically thinned chiasm, and an
      absent septum pellucidum. Monocular temporal visual field loss from organic
      lesions is quite rare but has been reported in conjunction with compressive
      lesions at the optic nerve-optic chiasm junction. This is the first report to
      demonstrate this visual field defect together with bowtie optic nerve hypoplasia.

PMID- 16966941
TI  - Subretinal hemorrhage from a peripapillary choroidal neovascular membrane in
      papilledema caused by idiopathic intracranial hypertension.
AB  - A 42-year-old man with idiopathic intracranial hypertension and chronic
      papilledema had severe visual loss in his left eye caused by subretinal bleeding
      from a peripapillary choroidal neovascular membrane (CNVM). After optic nerve
      sheath fenestration in his left eye, the papilledema improved, allowing improved
      visualization of the CNVM. Visual function did not improve after the surgery.
      CNVM can complicate chronic papilledema and account for sudden worsening of
      vision. The appropriate management of this type of CNVM is unresolved.

PMID- 16966942
TI  - New concepts in the diagnosis and management of optic nerve sheath meningioma.
AB  - Optic nerve sheath meningiomas are by far the most common tumors of the optic
      nerve sheath. The diagnosis can be suspected in most cases from clinical findings
      and supported by the results of neuroimaging, obviating tissue biopsy in the
      majority of cases. Observation may be appropriate in patients with mild or no
      visual deficit or in whom visual loss is not progressing, whereas stereotactic
      fractionated radiation therapy has been demonstrated to improve or stabilize
      vision in progressive or advanced cases. Attempts at surgical excision, and even
      biopsy, of optic nerve sheath meningiomas are associated with a high risk of
      blindness and should be reserved for the rare case of an anteriorly located,
      primarily exophytic tumor with focal involvement of the dural sheath.

PMID- 16966943
TI  - Pupil abnormalities in selected autonomic neuropathies.
AB  - Examination of the pupil provides an opportunity to detect disturbances in the
      autonomic innervation of the eye. The pupil is frequently affected in patients
      with generalized autonomic neuropathies. This literature review confirms a high
      prevalence of sympathetic deficits and parasympathetic deficits in acute or
      subacute dysautonomia, diabetes, amyloidosis, pure autonomic failure,
      paraneoplastic syndromes, Sjogren syndrome, familial dysautonomia, and dopamine
      beta-hydroxylase deficiency. It confirms the relative scarcity of a pupil
      abnormality in patients with multiple system atrophy. There are difficulties in
      clinical diagnosis of pupil abnormalities and interpretation of pupil
      pharmacologic tests, particularly when combined sympathetic and parasympathetic
      deficits are present.

PMID- 16966944
TI  - The annual meeting of the Association for Research in Vision and Ophthalmology,
      Fort Lauderdale, Florida April 30-May 4, 2006.

PMID- 16966945
TI  - The 58th annual meeting of the American Academy of Neurology San Diego,
      California April 1-8, 2006.

PMID- 16966946
TI  - Horner syndrome and ipsilateral abduction deficit attributed to giant cell
      arteritis.

PMID- 16966947
TI  - Mydriasis and accommodative failure from exposure to topical glycopyrrolate used
      in hyperhidrosis.

PMID- 16966949
TI  - Mechanism of bitemporal hemianopia.

PMID- 16966952
TI  - Truckers with OSA, should they be driving?

PMID- 16966953
TI  - An investigation of the effects of a healthcare provider network on costs and
      lost time in workers' compensation.
AB  - OBJECTIVE: The objective of this study was to evaluate the number of lost time
      days and cost of workers' compensation claims at a median claim duration
      (maturity) of 25 months for individuals injured between August 1, 2003, and July
      31, 2004, who chose a statewide (Louisiana) network (Omnet Gold) of healthcare
      providers not subject to utilization review. METHODS: We identified and
      contrasted 176 lost time claims (143 closed) managed by Omnet Gold (OG)
      healthcare providers and 1464 lost time claims managed by healthcare providers
      not participating in OG. RESULTS: The average frequency of lost workdays for a
      closed OG claim was 53 days versus 99 days for a closed non-OG claim and the
      average cost of a closed OG claim was 12,554 dollars, whereas the average cost of
      a closed non-OG claim was 20,400 dollars. Both days lost from work and costs were
      significantly lower among claims managed by OG healthcare providers. This outcome
      was consistent with the findings of a previous study performed on the same claims
      in which a significant difference was demonstrated analyzing primarily open
      (unresolved) claims with a median claim duration of 6 months. The ability of OG
      healthcare providers to return a higher proportion of injured workers to work
      early and shorten claims durations were the major factors influencing these
      outcomes. CONCLUSIONS: In a state where claimants are permitted choice of medical
      provider, a network of healthcare providers can achieve superior lost time and
      cost outcomes than out of network healthcare providers.

PMID- 16966954
TI  - Cancer incidence in Florida professional firefighters, 1981 to 1999.
AB  - OBJECTIVE: The objective of this study was to examine the cancer risk associated
      with firefighting. METHODS: Standardized incidence ratio analysis (SIR) was used
      to determine the relative cancer risk for firefighters as compared with the
      Florida general population. RESULTS: Among 34,796 male (413,022 person-years) and
      2,017 female (18,843 person-years) firefighters, 970 male and 52 female cases of
      cancer were identified. Male firefighters had significantly increased incidence
      rates of bladder (SIR = 1.29; 95% confidence interval = 1.01-1.62), testicular
      (1.60; 1.20-2.09), and thyroid cancers (1.77; 1.08-2.73). Female firefighters had
      significantly increased incidence rates of overall cancer (1.63; 1.22-2.14),
      cervical (5.24; 2.93-8.65), and thyroid cancer (3.97; 1.45-8.65) and Hodgkin
      disease (6.25; 1.26-18.26). CONCLUSIONS: Firefighting may be associated with an
      increased risk of selected site-specific cancers in males and females, including
      an overall increased cancer risk in female firefighters.

PMID- 16966955
TI  - Effectiveness of an incentive-based online physical activity intervention on
      employee health status.
AB  - OBJECTIVE: The objective of this study was to test whether a financial incentive
      integrated with health benefits for an online physical activity program was
      associated with increased employee participation and improved health status among
      participants compared with nonparticipants. METHODS: Participation in the Virtual
      Fitness Center (VFC), an online physical activity program associated with a 150
      dollars cash rebate, was assessed. Risk status for 2004 VFC participants and
      nonparticipants was compared using a health risk appraisal. RESULTS: A total of
      53.8% of total eligible employees were VFC participants and reduced their risk
      for physical inactivity (8.4% points), life dissatisfaction (2.1), low perception
      of health (1.9), high risk status (1.3), smoking (0.4), and high body weight
      (0.2). CONCLUSIONS: Providing a cash incentive is one strategy for encouraging
      VFC participation and eliciting improved health status in an employer-sponsored,
      web-based physical activity program.

PMID- 16966956
TI  - Financial costs due to excess health risks among active employees of a utility
      company.
AB  - OBJECTIVE: The objective of this study was to examine the health risk-related
      excess costs of time away from work, medical claims, pharmacy claims, and total
      costs with and without considering the prevalence of health risks. METHODS: A
      total of 2082 of 4266 employees of a Midwest utility participated in a health
      risk appraisal (HRA). Individuals were classified by their HRA participation
      status and also by 15 health risks. Total and excess costs were analyzed for all
      employees. RESULTS: There were significant excess costs due to individual risks
      and overall excess health risks in all cost measures. Both excess cost per risk
      and prevalence of the risk were important factors in determining the excess costs
      in the population. As compared with low-risk participants, HRA nonparticipants
      and the medium- and high-risk participants were 1.99, 2.22, and 3.97 times more
      likely to be high cost status. CONCLUSIONS: Approximately one third of corporate
      costs in medical claims, pharmacy claims, and time away from work could be
      defined as excess costs associated with excess health risks.

PMID- 16966957
TI  - Effects of a smoke-free law on hair nicotine and respiratory symptoms of
      restaurant and bar workers.
AB  - OBJECTIVE: Bar and restaurant workers' exposure to secondhand smoke (SHS) was
      compared before and 3 and 6 months after implementation of a smoke-free
      ordinance. METHODS: Hair nicotine, self-reported exposure to SHS, and respiratory
      symptoms were assessed on 105 smoking and nonsmoking workers from randomly
      selected establishments in Lexington, Kentucky. Thirty-eight percent were current
      smokers with more than half smoking 10 or fewer cigarettes per day. Workers
      provided a hair sample at baseline and at the 3-month interview. RESULTS: There
      was a significant decline in hair nicotine 3 months postlaw when controlling for
      cigarettes smoked per day. Bar workers showed a significantly larger decline in
      hair nicotine compared with restaurant workers. The only significant decline in
      SHS exposure was in the workplace and other public places. Regardless of smoking
      status, respiratory symptoms declined significantly postlaw. CONCLUSIONS:
      Hospitality workers demonstrated significant declines in hair nicotine and
      respiratory symptoms after the law. Comprehensive smoke-free laws can provide the
      greatest protection to bar workers who are the most vulnerable to SHS exposure at
      work.

PMID- 16966958
TI  - Underreporting of work-related injury or illness to workers' compensation:
      individual and industry factors.
AB  - OBJECTIVE: We quantified the underreporting of work-related injury or illness to
      workers' compensation (WC). METHODS: Using data from 2612 wage-earning
      respondents who participated in the 2002 Washington State Behavioral Risk Factor
      Surveillance System, we assessed work-related injury or illness in the previous
      year and identified the factors associated with WC claim filing by logistic
      regression. RESULTS: The self-reported rate of work-related injury or illness of
      respondents was 13%. Among those who had a work-related injury or illness, 52%
      filed a WC claim. After adjustment for age, gender, and race, those who filed WC
      claims were more likely to be overweight and married. WC claim filing varies
      considerably across industry and occupation groups holding all other measured
      factors constant. CONCLUSIONS: Individual and industry/occupation factors are
      related to underreporting of work-related injury or illness to the WC system.

PMID- 16966959
TI  - Multilevel analysis of workplace and individual risk factors for long-term
      sickness absence.
AB  - OBJECTIVE: The objective of this study was to examine if psychosocial and
      physical work-environment factors predict long-term sickness absence (>8 weeks)
      at both the individual and the workplace level. MATERIAL AND METHODS: Data were
      collected in a prospective study in 52 Danish workplaces. Psychosocial factors
      were aggregated as workplace means. We used multilevel logistic regression models
      with psychosocial factors as predictors of long-term sickness absence over 5
      years based on data from a national absence register. RESULTS: Long-term sickness
      absence was predicted by physical work-environment factors at the individual
      level and psychosocial work environment factors at the workplace level.
      Interaction between the individual physical and workplace-level psychosocial risk
      factors was found. CONCLUSION: Workplace-based absence reduction interventions
      can be enhanced by concurrently addressing the individual and the workplace
      level.

PMID- 16966960
TI  - Associations between exposure to polycyclic aromatic hydrocarbons and temporal
      change of urinary 1-hydroxypyrene levels in Taiwanese coke-oven workers.
AB  - OBJECTIVES: Our aim is to analyze the association between polycyclic aromatic
      hydrocarbon (PAH) exposure and the temporal change of urinary 1-hydroxypyrene (1
      OHP). METHODS: Two personal air samples, eight spot urine samples, and
      questionnaires were used to collect PAH exposure, urinary 1-OHP, demographic
      data, and environmental pollutants. RESULTS: Topside-oven workers had
      significantly higher levels of PAH exposure and 1-OHP than side-oven workers.
      Urinary 1-OHP was a biomarker for PAH exposure. In topside-oven workers, the
      trend of 1-OHP increased sharply and reached the top in the sixth day after work
      and declined dramatically on days off. In side-oven workers, such a trend was not
      found, and those who smoked showed a slight increase in urinary 1-OHP levels on
      days off. CONCLUSIONS: We suggest that the pattern of temporal change of urinary
      1-OHP levels is different between topside-oven and side-oven workers.

PMID- 16966961
TI  - Use of beryllium lymphocyte proliferation testing for screening of asymptomatic
      individuals: an evidence-based assessment.
AB  - OBJECTIVE: We reviewed published data describing use of beryllium lymphocyte
      proliferation testing (BeLPT) to determine the appropriateness of BeLPT for
      screening asymptomatic individuals. METHODS: Published studies were identified by
      computerized literature searches and hand searches of relevant bibliographies and
      cited references. Critical assessment of evidence focused on five elements
      essential to judging effectiveness of preventive services: 1) burden of
      suffering, 2) accuracy and reliability of screening tests, 3) effectiveness of
      early detection, 4) harms of screening, and 5) benefits outweighing harms.
      RESULTS: Important gaps and deficiencies in the evidence were found. The
      prevalence of beryllium sensitization and chronic beryllium disease in
      asymptomatic individuals are unknown. The accuracy and reliability of BeLPT are
      uncertain. Marked intra- and interlaboratory variability has been reported. The
      clinical benefits of early intervention have not been confirmed or quantified in
      asymptomatic individuals. CONCLUSIONS: There is currently insufficient scientific
      evidence to support the use of BeLPT for routine screening of asymptomatic
      individuals.

PMID- 16966962
TI  - Nasal air sampling for measuring inhaled wheat allergen in bakeries with and
      without facemask use.
AB  - OBJECTIVE: Occupational asthma caused by flour is common in bakers. We applied
      novel intranasal air samplers (INAS) to assess wheat allergen exposure and
      evaluate respiratory protection in bakeries. METHODS: Two models of INAS (INAS-M1
      and INAS-M2) were compared with simultaneous personal air sampling of inhalable
      dust, both with and without facemasks. Wheat allergen levels were measured using
      a sensitive sandwich enzyme immunoassay. Allergenic particles were immunostained
      for microscopic visualization. RESULTS: Personal air sampling correlated well
      with INAS-M1 (r = 0.89) and INAS-M2 (r = 0.75). INAS-M2 collected particles more
      effectively than INAS-M1. Facemasks reduced inhalation of wheat allergen by 96%
      and 93% measured using INAS-M1 and INAS-M2, respectively. CONCLUSIONS: Nasal air
      sampling can complement personal air sampling to measure short-term exposure and
      evaluate respiratory protection. To prevent baker's asthma, facemasks may be an
      effective solution in addition to improving workplaces.

PMID- 16966963
TI  - Cancer mortality among textile workers in Shanghai, China: a preliminary study.
AB  - OBJECTIVE: We assessed the association between cotton textile work and cancer
      mortality. METHODS: The cancer mortality experience of 912 (444 cotton, 468 silk)
      textile workers in Shanghai, China, was compared. Workers were followed from 1981
      to 2003. The associations between cotton textile work and death due to all
      cancers combined (with and without lung cancer) and to gastrointestinal cancers
      were estimated with Cox models, adjusting for age, work years, and pack-years.
      RESULTS: There were 69 deaths. The adjusted hazard rate ratio (HR) was 2.10 (95%
      confidence interval [CI], 0.98-4.47) for all cancers combined and 2.56 (95% CI,
      1.14-5.74) after excluding lung cancer. For gastrointestinal cancers, the
      adjusted HR was 2.09 (95% CI, 0.83-5.27). CONCLUSIONS: These preliminary data
      suggest that, with the exception of lung cancer, cotton workers have
      significantly higher cancer mortality rates than silk workers.

PMID- 16966965
TI  - Preventing needless work disability by helping people stay employed.

PMID- 16966964
TI  - Fall-related injuries among agricultural household members: Regional Rural Injury
      Study II (RRIS-II).
AB  - OBJECTIVE: The objective of this study was to identify the magnitude and
      consequences of and potential risk factors for fall-related injuries among
      agricultural operation households. METHODS: Demographic, injury, and exposure
      data were collected through 1999 from 3765 households in a five-state region. A
      causal model facilitated survey design, data analyses, and interpretation of
      results; directed acyclic graphs guided multivariate modeling. RESULTS: The
      16,538 participants experienced 766 fall-related injury events (48.3 per 1000
      persons). Consequences included lost agricultural and other work time. Increased
      risks involved residence in states other than Minnesota, male gender, and injury
      history. Decreased risks were among those less than 35 years of age and those who
      worked 40 hours or less per week. CONCLUSIONS: Fall-related injury is a major
      problem for the agricultural population. This effort serves as a basis for
      further in-depth research.

PMID- 16966966
TI  - Occupational Medicine Forum. What are the major points to consider for review of
      heavy metal toxicity? Part 1.

PMID- 16966968
TI  - Disease prevention through antismoking efforts.

PMID- 16966969
TI  - Newer treatment options for patients with moderate-to-severe psoriatic disease.

PMID- 16966970
TI  - Searching and critiquing literature essential for acute care NPs.

PMID- 16966971
TI  - A 70-year-old woman with muscle weakness and pain.

PMID- 16966972
TI  - Menopause: studying the research.

PMID- 16966974
TI  - Improving outcomes for COPD patients.

PMID- 16966976
TI  - Enhancing women's mood and energy.

PMID- 16966977
TI  - RotaTeq for prevention of rotavirus gastroenteritis.

PMID- 16966982
TI  - Effectiveness of brief interventions after alcohol-related vehicular injury: A
      randomized controlled trial.
AB  - BACKGROUND: Because 40% of motor vehicle fatalities in the United States are
      alcohol-related, interventions delivered by trauma clinicians targeted to reduce
      drinking are of particular importance to public health. The objective of this
      study was to test the effectiveness of hospital-based brief intervention
      strategies to reduce alcohol consumption and other health-related outcomes in the
      year after an alcohol-related vehicular injury. Brief interventions are
      clinically based strategies including assessment and direct feedback about
      drinking alcohol, goal setting, behavioral modification techniques, and the use
      of a self-help manual. METHODS: The study was a randomized controlled trial of
      two types of brief intervention with a 12-month follow-up. Participants with
      alcohol-related vehicular injury who were admitted to Level I trauma centers were
      eligible for enrollment. Enrolled participants were randomized to a control,
      simple advice, or brief counseling condition. Primary outcome variables were
      alcohol consumption (standard drinks/month, binges/month), adverse driving events
      (driving citations, traffic crashes), and changes in health status (hospital and
      emergency department admissions). RESULTS: The study enrolled 187 participants at
      baseline and retained 100 across 12 months. Participants had a significant
      decrease in alcohol consumption and traffic citations at 12 months as compared
      with baseline. Mean standard drinks/month declined from 56.80 (SD 63.89) at
      baseline to 32.10 (SD 53.20) at 12 months. Mean binges/month declined from 5.79
      (SD 6.98) at baseline to 3.21 (SD 6.17) at 12 months. There were no differences
      in alcohol consumption, adverse driving events, or health status by condition.
      CONCLUSIONS: Whether the reductions in alcohol consumption and traffic citations
      were a result of the crash, hospitalization for injury, screening for alcohol
      use, or combination of these factors is difficult to determine. Further work is
      needed to understand the mechanisms involved in reductions of health-related
      outcomes and the role of brief intervention in this population.

PMID- 16966983
TI  - Hospital-based violence intervention programs work.
AB  - BACKGROUND: Hospital-based violence prevention programs have emerged at trauma
      centers nationwide; however, none has been thoroughly evaluated for
      effectiveness. Our Violence Intervention Program (VIP) conducted a prospective
      randomized control study to evaluate the effectiveness of intervention for repeat
      victims of violence. METHOD: Patients admitted between 1999 and 2001 for
      treatment of injuries inflicted by a violent act were identified. Repeat victims
      of violence on parole/probation were invited to join the study. Participants were
      given a history-gathering questionnaire and randomized into two groups. Cases
      (intervention [n = 56]) received intensive psychosocial follow-up services,
      family or group therapy, and assisted with substance abuse treatment. Controls
      (nonintervention [n = 44]) received standard medical treatment and follow-through
      in accordance with standard parole or probation procedures. RESULTS: There was no
      significant difference in the number of arrests in the two groups. The control
      group was three times more likely to be arrested for a violent crime, two times
      more likely to be convicted of any crime, and four times more likely to be
      convicted of a violent crime. The projected time of incarceration is
      significantly longer for the control group. Repeat violent criminal activity was
      significantly more evident in the control group. CONCLUSION: Significant
      differences exist between the VIP intervention and nonintervention groups in
      terms of the quantity and severity of criminal activity.

PMID- 16966984
TI  - Splenic artery embolization: Have we gone too far?
AB  - BACKGROUND: Splenic artery angioembolization (EMBO) has been promoted to increase
      the success rate of nonoperative management of splenic injuries. Our
      institutional clinical pathway calls for EMBO in the setting of ongoing splenic
      bleeding or contrast blush on computed tomography scan. We perceived a higher
      rate of failure than that reported in the literature. The purpose of this study
      was to review our experience with splenic EMBO to identify predictors of failure
      of nonoperative/EMBO management. METHODS: The trauma registry and interventional
      radiology database of a Level I trauma center were reviewed for patients with
      splenic injuries from January 2000 through June 2004. Charts and films of
      patients undergoing EMBO were reviewed. RESULTS: There were 221 patients admitted
      with blunt splenic injuries. Of these, 165 (75%) were selected for nonoperative
      management; 41 (25%) of them underwent splenic EMBO. Of the 41, 11 patients (27%)
      failed nonoperative/EMBO management. Of nine patients with low-grade injury (I,
      II) and small or no hemoperitoneum, none failed EMBO, whereas 10 of 23 (43%) with
      high-grade injury (III, IV, V) and moderate or large hemoperitoneum failed. EMBO
      was more likely to fail if extravasation was seen on angiography (59% vs. 4%).
      Coils (vs. particles) and main (vs. selective) artery EMBO were more often
      successful. Of EMBO patients who experienced transient hypotension, 57% required
      splenectomy. CONCLUSIONS: EMBO may have salvaged many spleens, but splenectomy
      was required in 27% of EMBO patients. Patient selection is critical to successful
      management. Any hypotension in the face of a contrast blush probably warrants
      laparotomy. The combination of high grade injury and significant hemoperitoneum,
      or extravasation on angiogram, predict a high risk of failure and thus warrant a
      low threshold for splenectomy if bleeding persists. Technical EMBO considerations
      may impact success, but this requires further investigation.

PMID- 16966985
TI  - The CT risk factors for the need of operative treatment in initially
      hemodynamically stable patients after blunt hepatic trauma.
AB  - BACKGROUND: Most hemodynamically stable blunt hepatic trauma (BHT) patients are
      treated nonoperatively with a reported successful rate exceeding 80%. It is
      current clinical consensus that hemodynamic stability is the only determinant for
      a patient to be managed nonoperatively. However, conversion to operative
      treatment was found in around 10% of these patients. METHODS: There were 214
      computed tomography (CT) scans of hemodynamically stable patients with main or
      sole BHT studied. CT findings including injury severity grading, contrast
      extravasation, the amount of hemoperitoneum, the degree of maceration, the depth
      of laceration, the size of hematoma, and the involvement of great vessels were
      analyzed to determine risk factors leading to the need of operative treatment.
      RESULTS: Intraperitoneal contrast extravasation, hemoperitoneum in six
      compartments, maceration >2 segments, high Mirvis' CT grade as well as American
      Association for the Surgery of Trauma injury scale, laceration > or =6 cm in
      depth, and porta hepatis involvement occurred significantly more frequently (p <
      or = 0.001, respectively) in patients who needed operative treatment. Logistic
      regression analysis identified "intraperitoneal contrast extravasation" (RR =
      12.5, 95% CI: 7.8-20.0; p < 0.001) and "hemoperitoneum in six compartments" (RR =
      22, 95% CI: 9.7-49.4; p < 0.001) to independently contribute to the need of
      operative treatment. CONCLUSION: Intraperitoneal contrast extravasation and
      hemoperitoneum in six compartments on CT scan both indicate massive or active
      hemorrhage and should be regarded as high risk for the need of operation in
      hemodynamically stable patients after BHT. Patients with low risk profile can be
      successfully treated with nonoperative modalities.

PMID- 16966986
TI  - Residents managed trauma adequately using their own radiological interpretation
      as compared with "nighthawk" radiologists.
AB  - OBJECTIVE: To determine whether senior surgical residents can independently
      interpret radiologic studies for the trauma patients under their care. METHOD:
      Five senior surgical residents (PGY-4 and -5) participated in this prospective
      study. The residents independently read trauma films as part of the emergency
      assessment, documenting their interpretations to be compared with the reports by
      nighthawk radiologists. RESULTS: During a period of 4 months, 426 films of 124
      trauma patients admitted to a Level II trauma center were read by one of the five
      senior surgical residents, and by nighthawk radiologists. Approximately 22% of
      these were penetrating injuries and the remainder blunt trauma. Residents
      identified 127 injuries versus 128 injuries identified by the radiologists, with
      99.2% agreement. The residents missed two injuries, while the radiologists missed
      one. CONCLUSIONS: Senior surgical residents can independently and accurately
      interpret the trauma radiology studies, a skill essential for time-critical
      decision making.

PMID- 16966987
TI  - Indications for CT scanning in mild traumatic brain injury: A cost-effectiveness
      study.
AB  - BACKGROUND: There is considerable uncertainty about the indications for cranial
      computed tomography (CT) scanning in patient with minor traumatic brain injury
      (TBI). This analysis involves an evidence-based comparison of several strategies
      for selecting patients for CT with regard to effectiveness and cost. METHODS: We
      performed a structured literature review of mild traumatic brain injury and
      constructed a cost-effectiveness model. The model estimated the impact of missed
      intracranial lesions on longevity, quality of life and costs. Using a 20-year-old
      patient for primary analysis, we compared the following strategies to screen for
      the need to perform a CT scan: observation in the emergency department or
      hospital floor, skull radiography, Selective CT based on the presence of
      additional risk factors and scanning all. RESULTS: Outcome measures for each
      strategy included average years of life, quality of life and costs. Selective CT
      and the CT All policy performed significantly better than the alternatives with
      respect to outcome. They were also less expensive in terms of total direct health
      care costs, although the differences did not reach statistical significance. The
      model yielded similar, but smaller, differences between the selective imaging and
      other strategies when run for older patients. CONCLUSIONS: Although the incidence
      of intracranial lesions, especially those that require surgery, is low in mild
      TBI, the consequences of delayed diagnosis are forbidding. Adverse outcome of an
      intracranial hematoma is so costly that it more than balances the expense of CT
      scans. In our cost-effectiveness model, the liberal use of CT scanning in mild
      TBI appears justified.

PMID- 16966988
TI  - Retrospective evaluation of anemia and transfusion in traumatic brain injury.
AB  - BACKGROUND: Despite clear evidence in critical care that blood transfusion has an
      adverse impact on outcome, neurosurgical textbooks still recommend transfusion of
      patients with traumatic brain injury (TBI) to a hematocrit (HCT) of 30%. There is
      little empirical evidence to support this practice. The current study addresses
      transfusion requirements in TBI in terms of neurologic outcome. METHODS:
      Retrospective record review of patients with severe TBI. Outcome measures were
      Glasgow Coma Scale score (GCS), Glasgow Outcome Score (GOS), and Ranchos Los
      Amigos Score (RLA) at hospital discharge (D/C); and GOS and Functional
      Independence Measures at follow-up. Association of outcomes with the number of
      days the HCT <30% and lowest measured HCT were evaluated. RESULTS: In all, 169
      patients reviewed; 150 with D/C outcome data and 72 with long-term follow-up
      data. Univariate analysis showed that lowest measured HCT was associated with
      lower D/C GCS, D/C GOS, and RLA scores. Linear regression showed that more days
      with HCT <30% were associated with improved neurologic outcomes measured by GOS
      (R2 = 0.424, p < 0.001), GCS (R2 = 0.381, p < 0.001) and RLA (R2 = 0.392, p <
      0.001) scores on D/C. Both transfusion and lowest measured HCT were significantly
      associated with all lower outcome scores on D/C. Additional factors with adverse
      impact on outcome were head Abbreviated Injury Score (AIS), Injury Severity
      Score, hyperglycemia, and hypotension. Long-term outcomes were only significantly
      associated with head AIS. CONCLUSIONS: Patients with severe TBI should not have a
      different transfusion threshold than other critical care patients. Prospective
      studies are needed to evaluate the effects of anemia in TBI.

PMID- 16966989
TI  - Obesity and traumatic brain injury.
AB  - BACKGROUND: As obesity continues to run rampant in our society, an understanding
      of its adverse effect after traumatic injury is starting to unfold. We
      hypothesize that obesity negatively impacts head-injured patients, and the
      current study intends to compare obese and lean patients with traumatic brain
      injury (TBI). METHODS: This is a retrospective study evaluating all blunt trauma
      patients with TBI admitted to the intensive care unit (ICU) in our urban, Level I
      trauma center from 1998 until 2003. Body mass index (BMI) was used to categorize
      patients as either lean (BMI <30 kg/m2) or obese (BMI > or =30 kg/m2). Admission
      demographics, type and severity of head injury, and associated injuries were
      recorded for each patient. Primary outcome was mortality, while secondary
      outcomes were cause of death, complications, and for survivors, days of
      mechanical ventilation, ICU length of stay, and hospital length of stay. Obese
      and lean patients were compared using univariate analysis and multivariate
      stepwise logistic regression. In addition, a subgroup analysis of patients with
      isolated head injury was performed. RESULTS: There were 690 patients with TBI
      admitted to the ICU during the study period, with 129 (19%) obese patients (BMI =
      34 +/- 5 kg/m2) and 561 (81%) lean patients (BMI = 24 +/- 4 kg/m2). The two
      groups were similar with the exceptions that obese patients were older (46 +/- 20
      years versus 39 +/- years, p < 0.01), had lower admission systolic blood pressure
      (125 +/- 38 mm Hg versus 134 +/- 30 mm Hg, p = 0.01), and more often sustained an
      associated chest injury (46% versus 35%, p = 0.03). Obese patients with TBI had a
      trend toward more complications (34% versus 28%, p = 0.17) and a higher mortality
      (36% versus 25%, p = 0.02). However, stepwise logistic regression failed to
      identify obesity as an independent risk factor for either morbidity or mortality.
      In addition, obese patients with isolated head injury had no increase in
      complications or death. CONCLUSIONS: Although obese patients suffer more
      complications and higher mortality than lean patients after TBI, this adverse
      effect seems to be due to age, lower admission blood pressure, and more
      associated chest injury, rather than a direct result of the obese state.

PMID- 16966990
TI  - Delayed intracranial complications after concussion.
AB  - BACKGROUND AND METHODS: The incidence of readmissions because of delayed
      intracranial complications within 3 weeks after observation for the sole
      diagnosis of concussion was examined in a national cohort. A nested case-control
      design was used to analyze the association between clinical factors as well as
      early computed tomography (CT) scan examination and these complications. RESULTS:
      Out of 100,784 patients hospitalized because of concussion during ten years, 127
      (0.13%) patients were readmitted because of a delayed intracranial complication.
      High clinical severity grade (odds ratio [OR] 2.0, confidence interval [CI] 1.2
      3.6), minor CT scan abnormalities (OR 1.7, CI 0.8-3.4) and male gender (OR 2.2,
      CI 1.4-3.5) were associated with an increased risk of delayed, intracranial
      complications. CONCLUSION: The incidence of delayed intracranial complications
      after primarily uncomplicated concussion was low. High clinical severity grade
      and male gender were risk factors. We failed to demonstrate an additional value
      of the acute CT scan examination to predict these complications.

PMID- 16966991
TI  - Blind subxiphoid pericardiotomy for cardiac tamponade because of acute
      hemopericardium.
AB  - OBJECTIVE: Percutaneous catheter drainage (PCD) is not always effective in a case
      of hemopericardium. Acute occlusion of catheter and cardiac perforation can
      happen more often. To perform subxiphoid pericardiotomy within a minute for
      emergency cases, we have done this procedure in a blind method after finger
      dissection by subxiphoid approach. We report the usefulness of blind subxiphoid
      pericardiotomy (BSP) based on the results of a prospective control study.
      METHODS: We designed a study to determine a favorable management for cardiac
      tamponade resulting from hemopericardium. In an emergency case of cardiac
      tamponade because of hemopericardium, board certified surgeons should perform BSP
      and other emergency physicians should perform PCD, with or without local
      anesthesia. PCD (n = 67) and BSP (n = 16) were performed for patients with cardio
      pulmonary arrest (CPA) or near CPA because of cardiac tamponade secondary to
      trauma (n = 7), acute aortic dissection (n = 65), and cardiac rupture following
      acute myocardial infarction (n = 11) in our emergency medical center from January
      2000 to December 2004. RESULTS: BSP was effective in all cases but PCD was
      ineffective in five cases because of clotting in pericardium (p = 0.260). No
      complication was observed in the BSP group but five critical complications and
      three infeasible drainage complications were observed in the PCD group (p =
      0.146). Ten patients (BSP, 4; PCD, 6; p = 0.077) survived after emergency surgery
      (n = 8) or conservative treatment (n = 2). CONCLUSION: BSP was safe and could be
      performed quickly in an emergency situation. Percutaneous catheter drainage for
      hemopericardium could not avoid critical complications because of clotting in
      pericardium.

PMID- 16966992
TI  - An experimental cadaveric study for a better understanding of blunt traumatic
      aortic rupture.
AB  - BACKGROUND: Blunt traumatic aortic rupture (BTAR) is a common catastrophic injury
      leading to death. Considerable uncertainty remains regarding the pathogenic
      cause. This study examines the comportment of the heart and the aorta during a
      frontal deceleration. METHODS: Accelerometers were placed in the right ventricle
      of the heart, the aorta, the sternum, and the spine of six trunks removed from
      human cadavers. Different vertical decelerations were applied to cadavers and the
      relative motion of these organs was studied (19 tests). RESULTS: The deceleration
      recorded in the isthmus of the aorta was always higher that the one recorded in
      the heart (p < 0.05). The difference of deceleration was 17% and increased with
      the speed's fall (extremes 5-25%). There was no significant difference of
      deceleration between the bony structures of the thorax. These results
      experimentally demonstrate for the first time that the fundamental mechanism of
      BTAR is sudden stretching of the isthmus of the aorta. CONCLUSION: Four
      mechanisms are suspected to explain the location of the rupture: two hemodynamic
      mechanism (sudden increase of intravascular pressure and the water-hammer
      effect), and two physical mechanisms (sudden stretching of the isthmus and the
      osseous pinch). A greater understanding of the mechanism of this injury could
      improve vehicle safety leading to a reduction in its incidence and severity.
      Future work in this area should include the creation of an inclusive, dynamic
      model of computer-based modeling systems. This study provides for the first time
      physical demonstration and quantification of the stretching of the isthmus,
      leading to a computerized model of BTAR.

PMID- 16966993
TI  - Crash analysis of lower extremity injuries in children restrained in forward
      facing car seats during front and rear impacts.
AB  - BACKGROUND: The mechanism, crash characteristics, and spectrum of lower extremity
      injuries in children restrained in forward-facing car seats during front and rear
      impacts have not been described. METHODS: We identified in two databases children
      who sustained lower extremity injuries while restrained in forward-facing car
      seats. To identify the mechanism, we analyzed crash reconstructions from three
      frontal-impact cases from the Crash Injury Research and Engineering Network. To
      further describe the crash and injury characteristics we evaluated children
      between 1 and 4 years of age with lower extremity injuries from front or rear
      impacts in the National Automotive Sampling System (NASS) Crashworthiness Data
      System (CDS) database. RESULTS: Crash reconstruction data demonstrated that the
      likely mechanism of lower extremity injury was contact between the legs and the
      front seatbacks. In the CDS database, we identified 15 children with lower
      extremity injuries in a forward-facing child seat, usually (13 out of 15) placed
      in the rear seat, incurred in frontal impacts (11 out of 15). Several (5 out of
      15) children were in unbelted or improperly secured forward-facing car seats.
      Injury Severity Scores varied widely (5-50). CONCLUSIONS: Children in forward
      facing car seats involved in severe front or rear crashes may incur a range of
      lower extremity injury from impact with the car interior component in front of
      them. Crash scene photography can provide useful information about anatomic sites
      at risk for injury and alert emergency department providers to possible subtle
      injury.

PMID- 16966994
TI  - Gene therapy with lipopolysaccharide binding protein for gram-negative pneumonia:
      respiratory physiology.
AB  - BACKGROUND: Lipopolysaccharide binding protein (LBP) plays an essential role in
      the pulmonary immune response to gram-negative bacterial infection. LBP knockout
      mice with gram-negative pneumonia have increased mortality compared with wild
      type controls. This mortality difference can be abolished with systemic LBP gene
      therapy. We postulate that LBP knockout mice will develop derangements in lung
      physiology from gram-negative pneumonia and that these changes can be reversed
      with systemic LBP gene therapy. METHODS: Twelve- to 16-week-old C57BL/6 wild-type
      mice and/or sex, age, matched LBP knockout mice were administered 1 x 10(3)
      colony-forming units/mouse of Klebsiella pneumoniae by intratracheal inoculation.
      Treated mice were administered 5 x 10(9) plaque-forming units of recombinant
      adenovirus containing either the gene for LBP or the irrelevant control protein
      beta-galactosidase by intravenous injection 2 days before bacterial inoculation.
      Respiratory physiology parameters were measured preinoculation and 24 hours
      postbacterial inoculation. RESULTS: Administration of LBP by systemic gene
      therapy to LBP knockout mice improved 7-day survival from Klebsiella pneumonia to
      a level equivalent to wild-type mice exposed to the same dose of bacteria (42 vs.
      43% survival). LBP knockout mice given the LBP gene therapy demonstrated
      increased 14-day survival from Klebsiella pneumonia when compared with controls
      treated with beta-galactosidase (28 vs. 0%, p < 0.001). LBP knockout mice
      developed significant differences in respiratory rate, minute ventilation, and
      enhanced pause (Penh), when compared with wild-type mice with Klebsiella
      pneumonia. These respiratory derangements were prevented with adenoviral delivery
      of the LBP gene before K. pneumoniae inoculation. CONCLUSIONS: Gram-negative
      pneumonia produces measurable changes in mortality and respiratory physiology
      between wild-type and LBP knockout mice. These changes can be prevented in LBP
      knockout mice by systemic gene therapy to restore innate immunity.

PMID- 16966995
TI  - Radiation exposure in trauma patients.
AB  - BACKGROUND: Trauma patients are exposed to a large amount of ionizing radiation.
      Radiologic examinations may include a multitude of plain films, computed
      tomography scans, and/or fluoroscopic examination. Previous studies have assessed
      radiation exposure to staff members at trauma centers, and in pregnant trauma
      patients. The purpose of the current study is to evaluate the amount of radiation
      to which trauma patients are exposed in a Level I trauma center. METHODS: The
      study used a prospective cohort design. All patients for whom a trauma code was
      activated between the months of September 2004 and July of 2005 were eligible to
      be enrolled in the study. Upon arrival to the trauma bay, a dosimeter badge, that
      measures ionizing radiation, was attached to a Velcro bracelet on the wrist of
      the patient. The badges were removed at the time of discharge from the hospital
      and analyzed. RESULTS: Data were collected on 224 patients (167 adults, 57
      pediatric). The median amount of radiation exposure to all patients equaled 68
      MREM (Interquartile range 31-181). A significant increase in the median amount of
      radiation exposure was found in patients with orthopedic injuries (107 MREM vs.
      45 MREM), an Injury Severity Score (ISS) >15 (107 MREM vs. 46 MREM), a length of
      stay >than 1 week (105 MREM vs. 65 MREM), age >18 (82 MREM vs. 44 MREM), and when
      >11 radiologic procedures were performed (127 MREM vs. 46 MREM). CONCLUSION:
      Trauma patients are being exposed to high amounts of radiation. Patients with
      orthopedic injuries, and those more severely injured, are at an increased risk.
      Further precautions to limit radiation exposure in this population are needed.

PMID- 16966996
TI  - Multiple, simultaneous trauma patients: Are they worse off?
AB  - BACKGROUND: The simultaneous management of multiple severely injured patients has
      the potential to overwhelm trauma center resources. We hypothesize that trauma
      patients presenting in clusters of two or more patients within a short time
      period have worse outcomes. METHODS: From the registry at our urban Level I
      trauma center, we reviewed 4,619 "major" trauma patients admitted during a span
      of 5.5 years (January 1998 through June 2003). A multidisciplinary team led by an
      in-house trauma surgery attending evaluated all patients. Pairs of two patients
      presenting less than 10 minutes apart (PAIRS) and clusters of three patients
      presenting within 30 minutes (CLUSTERS) were compared with patients arriving
      alone presenting over 4 hours apart (ALONE) and to other patients that did not
      meet any of the above criteria (OTHER). Multivariate regression was performed to
      determine differences in likelihood of direct operating room admissions,
      hospital, and intensive care unit (ICU) length of stay, and mortality. RESULTS:
      PAIRS made up 8.9% (413) and CLUSTERS made up 2.7% (126) of patients; 42% (1,939)
      arrived ALONE; 48.3% (2,229) of patients were classified as OTHER. Multivariate
      regression showed no significant differences in ICU or hospital length of stay,
      or mortality for PAIRS or CLUSTERS compared with patients presenting ALONE. PAIR
      and CLUSTER patients were more likely to undergo immediate surgery than the ALONE
      group (odds ratio 1.37, 95% confidence interval 1.03-1.83 and 1.61, 95% CI 1.00
      2.58, respectively). CONCLUSIONS: When PAIRS or CLUSTERS of seriously injured
      patients arrive in close time proximity, they are more likely to be directly
      admitted to the operating room than patients arriving ALONE. This difference in
      management does not appear to affect patient outcomes.

PMID- 16966997
TI  - Enhanced expression of intracellular heme oxygenase-1 in deactivated monocytes
      from patients with severe systemic inflammatory response syndrome.
AB  - BACKGROUND: Monocyte deactivation is an important contributor to infectious
      susceptibility in critically ill patients. However, the mechanism of monocyte
      deactivation has not been fully elucidated. Recently, intracellular heme
      oxygenese-1 (HO-1), an anti-inflammatory heat-shock protein, was reported to be
      activated by Toll-like receptors (TLRs), and to inhibit inflammatory cytokine
      production such as that of TNF-alpha. In the present study, we evaluated the
      expression of intracellular HO-1 and TLRs in monocytes from patients with severe
      systemic inflammatory response syndrome (SIRS) and examined the role of HO-1 in
      monocyte deactivation. PATIENTS: Twenty-seven patients who fulfilled the criteria
      for severe SIRS and had a serum C-reactive protein (CRP) level >10 mg/dL were
      included in this study. The cause of SIRS was sepsis in 16 patients, trauma in 7,
      and other in 4. Expression of intracellular HO-1, surface TLR2 and TLR4, and
      intracellular cytokines (TNF-alpha, Interleukin-6) stimulated via TLR activation
      were measured in circulating monocytes by flow cytometry. Intracellular HO-1
      expression was evaluated in normal monocytes stimulated with patient serum. Serum
      cytokine levels were also measured. Patient data were compared with data from
      healthy volunteers (n = 16). RESULTS: Cytoplasmic HO-1 was clearly detected by
      fluorescence microscopy. Expression of HO-1, TLR2, and TLR4 in monocytes was
      significantly enhanced in patients with severe SIRS compared with that in healthy
      volunteers, whereas intracellular TNF-alpha expression with peptidoglycan was
      significantly decreased (p < 0.05) in patients compared with that in healthy
      volunteers. HO-1 expression was significantly enhanced in normal monocytes
      stimulated with patient serum. Intracellular HO-1 levels were positively related
      to serum TNF-alpha levels in patients (r = 0.46). CONCLUSIONS: Expression of
      intracellular HO-1 and of TLRs was enhanced in deactivated monocytes from
      patients with SIRS. Increased production of intracellular HO-1 in response to
      serum factors may play a role in monocyte deactivation after systemic
      inflammation.

PMID- 16966998
TI  - Acidosis impairs the coagulation: A thromboelastographic study.
AB  - BACKGROUND: Coagulopathy is a contributor to and predictor of death in bleeding
      patients. Acidosis is known to be a predictor of worse outcome in trauma patients
      and to be a coexisting factor in coagulopathic patients, but it has not been
      studied if it is a causal factor in the development of coagulopathy. METHODS: We
      have adjusted the pH level in blood samples from healthy volunteers to different
      levels between 7.4 and 6.8 by the use of hydrochloric acid. Thereafter we have
      studied the coagulation at the different pH levels by the use of
      thromboelastography. RESULTS: We found a strong correlation between pH levels and
      impairment of the coagulation, where the clot strength is increased much slower
      at pH levels below 7.4 even though the initiation of the clotting seems to be
      normal. The clot formation time was increased by 168% at pH 6.8 as compared with
      pH 7.4 (p < 0.00001, r = 0.89) whereas the clotting time was left unaffected.
      CONCLUSIONS: Acidosis causes a strong impairment of the coagulation as measured
      with thromboelastography. The impairment found when lowering pH from 7.4 to 7.15
      was almost identical to the impairment seen in another study by Kettner et al.
      when the temperature was lowered from 36 degrees C to 32 degrees C.

PMID- 16966999
TI  - Arterial pulse pressure and its association with reduced stroke volume during
      progressive central hypovolemia.
AB  - BACKGROUND: The reduction of stroke volume (SV) during hemorrhage reflects the
      degree of blood loss, but accurate assessment of SV in bleeding patients in the
      field currently is not possible. In a previous pilot study, we reported that
      arterial pulse pressure and estimated sympathetic nerve activity (SNA) in trauma
      patients who died of hemorrhagic injuries was significantly lower than that
      observed in patients who did not die. For the current study, we measured mean
      arterial blood pressure (MAP), pulse pressure (PP), SV, and muscle sympathetic
      nerve activity (MSNA) in human subjects during progressive lower body negative
      pressure (LBNP) to test the hypothesis that a reduction in PP tracks the
      reduction of SV and change in MSNA during graded central hypovolemia in humans.
      METHODS: After a 12-minute baseline data collection period, 13 men were exposed
      to LBNP at -15 mm Hg for 12 minutes followed by continuous stepwise increments to
      -30, -45, and -60 mm Hg for 12 minutes each. RESULTS: Comparing baseline to -60
      mm Hg chamber decompression, systolic blood pressure (SBP) decreased (from 129 +/
      3.0 to 111 +/- 6.1 mm Hg; p = 0.005) and diastolic pressure was unchanged (78 +/
      3.0 versus 81 +/- 4.0 mm Hg; p = 0.55). Pulse pressure decreased (from 50 +/-
      2.5 to 29 +/- 4.0 mm Hg; p = 0.0001). LBNP caused linear reductions in PP and SV
      (from 125 +/- 9.2 to 47 +/- 6.4; r2 = 0.99), and increases in MSNA (from 14 +/-
      3.5 to 36 +/- 4.6 bursts/min; r2 = 0.96) without a significant change in MAP (r2
      = 0.28). PP was inversely correlated with MSNA (r2 = 0.88) and positively
      correlated with SV (r2 = 0.91). CONCLUSIONS: Reduced PP resulting from
      progressive central hypovolemia is a marker of reductions in SV and elevations in
      SNA. Therefore, when SBP is >90 mm Hg, PP may allow for early, noninvasive
      identification of volume loss because of hemorrhage and more accurate and timely
      triage.

PMID- 16967000
TI  - Evaluation of skin perfusion by use of indocyanine green video angiography:
      Rational design and planning of trauma surgery.
AB  - BACKGROUND: A very important aspect in the treatment of traumatic injuries is to
      determine the extent of skin involvement. Traditionally, this has involved
      clinical examinations, a more or less subjective technique. Therefore, various
      techniques, supplementing the clinical diagnosis, have been suggested, but none
      has yet achieved widespread clinical acceptance. Experiments have shown that the
      blood flow in injured tissue indicates the extent of tissue damage. METHODS: The
      clinical and scientific impact of Indocyanine green (ICG) video angiographies was
      tested in 40 patients. All kinds of depth and all kinds of causes of injury were
      included and analyzed. RESULTS: In all cases, it was possible to perform the ICG
      video angiography. Qualitative and quantitative measurements and observations
      correlated well with the extent and depth of the skin lesion, which was
      determined clinically (pre- and intraoperative assessment) and histologically
      (biopsies). CONCLUSION: Based on our experiences, we think that the ICG video
      angiography seems to be a very sensible and user-friendly device to detect the
      vascular patency of the skin. Our results indicate that laser induced ICG
      fluorescence angiography is a practical, accurate, and effective adjunct to
      clinical methods for evaluating skin perfusion and thereby, helpful to design and
      plan surgery.

PMID- 16967001
TI  - Local cooling restores microcirculatory hemodynamics after closed soft-tissue
      trauma in rats.
AB  - BACKGROUND: Severe closed soft-tissue injury (CSTI) results in progressively
      developing microvascular dysfunction and local inflammation. Cooling reduces
      swelling, pain, cellular oxygen demand, and metabolic activity. However, effects
      of cooling on posttraumatic microcirculation are not yet fully understood. Thus,
      we assessed effects of local cooling on microcirculation, regional inflammatory
      response including leukocyte-endothelial cell interaction, and edema formation
      after CSTI. METHODS: Standardized CSTI was induced by means of controlled impact
      injury in the left tibial compartment of 14 male Sprague-Dawley rats. Rats were
      assigned to four groups (n = 7 per group) as follows: group I, no trauma/no
      cooling; group II, no trauma/20 minutes of cooling; group III, 1.5 hours
      posttrauma/no cooling; and group IV, 1.5 hours posttrauma/20 minutes of cooling.
      RESULTS: CSTI resulted in a significant decrease in functional capillary density,
      a marked increase in microvascular permeability, and granulocyte infiltration
      (HIS48) as revealed by intravital microscopy and immunohistochemistry of the left
      extensor digitorum longus muscle. After 20 minutes of local cooling, these
      microvascular derangements were restored to the level of controls (group I).
      Edema (extensor digitorum longus muscle wet-to-dry weight ratio) was less
      pronounced compared with noncooling conditions (group III). Immunoreactivity for
      HIS48 (neutrophilic granulocytes) in injured rats subjected to local cooling
      (group IV) was markedly decreased compared with noncooling conditions (group
      III). CONCLUSION: These results provide in vivo evidence that cooling affords
      protection of posttraumatic microcirculation through sustained inhibition of
      microvascular and endothelial dysfunction leading to less granulocyte-dependent
      inflammation and skeletal muscle edema. Local cooling appears to reduce
      propagation of acute microvascular injury, preventing leukocyte-dependent tissue
      destruction and escalation of secondary tissue damage after musculoskeletal soft
      tissue trauma.

PMID- 16967002
TI  - The role of bifidobacteria in gut barrier function after thermal injury in rats.
AB  - BACKGROUND: Early multiple organ dysfunction syndrome appears to be facilitated
      with bacterial translocation in severe burn injury, yet the mechanisms of
      bacterial translocation remain in dispute. The aim of this study was to
      characterize the potential role of intestinal bifidobacteria in the pathogenesis
      of gut-derived bacterial translocation after burns and to analyze the effects of
      bifidobacterial supplement on gut barrier function. METHODS: Wistar rats were
      randomly divided into burn group (Burn, n = 60), sham burn group (SB, n = 10) in
      experiment 1, and burn + saline group (BS, n = 30), burn + bifidobacteria group
      (BB, n = 30), and sham-burn + saline group (SS, n = 30) in experiment 2. Animals
      in BB group were fed bifidobacterial preparation (5 x 10(9) CFU/mL) after burns,
      1.5 mL, twice daily. Animals in BS and SS were fed saline. Samples were taken on
      postburn days 1, 3, and 5. The incidence of bacterial translocation and counts of
      Bifidobacterium, fungi and Escherichia coli in gut mucosa, as well as the sIgA
      levels in mucus of the small intestine were determined. The positive sIgA
      expression in lamina propria and ileum mucosal injury were evaluated light
      microscopically by blinded examiners. RESULTS: The incidence of bacterial
      translocation was increased after burns, which was accompanied by significant
      decrease in number of bifidobacteria but significant increase in E. coli and
      fungi in gut mucosa, and elevation of levels of plasma endotoxin and IL-6 (p <
      0.001). The incidence of bacterial translocation was markedly reduced after 3-
      and 5-day supplementation of bifidobacteria compared with control group (p <
      0.05). The counts of mucosal bifidobacteria were increased by 4- to 40-fold,
      whereas E. coli and fungi were decreased by 2- to 30-fold and 10- to 150-fold,
      respectively, after bifidobacterial supplementation. The damage of mucosa tended
      to be less pronounced after 3-day bifidobacteria-supplemented formula compared
      with control group (grade 2 [0-6] versus grade 4 [3-6], p < 0.05). Moreover, the
      expression and release of sIgA was markedly augmented after 3-days of
      bifidobacteria-supplementation formula and it returned to normal range on
      postburn day 5. CONCLUSIONS: The decrease in counts and proportion of
      bifidobacteria to other flora in gut may play an important role in the
      development of bacterial translocation after thermal injury. Supplementation of
      exogenous bifidobacteria could improve gut barrier function, and attenuate
      bacterial/endotoxin translocation secondary to major burns.

PMID- 16967003
TI  - Uterine trauma in pregnancy after motor vehicle crashes with airbag deployment: A
      30-case series.
AB  - BACKGROUND: We describe a cohort of women of at least 20 weeks gestation to
      determine the frequency of placental abruption or fetal compromise after a motor
      vehicle crash (MVC) with airbag deployment. METHODS: A retrospective chart review
      was conducted at two urban emergency departments. All women of at least 20 weeks
      gestation with MVCs in which their airbag deployed and who were admitted for
      monitoring or trauma care between 1997 and 2002 were identified by the Trauma
      Registry for each hospital and included. RESULTS: Thirty women in the 6-year
      period were identified. Gestational age (GA) at the time of the MVC ranged from
      20 weeks to 37 weeks (median GA 29 weeks). Of the 30 women, 15 (50%) were belted
      drivers, 5 (17%) were unbelted drivers, 5 (17%) were belted front-seat
      passengers, and 5 (17%) were unbelted front-seat passengers. Median speed was 35
      mph. One woman experienced placental abruption with subsequent intrauterine fetal
      demise. Twenty-two (73%, 95% CI: 58-89) experienced uterine contractions. Sixteen
      (53%, 95% CI: 36-71) reported abdominal pain. Abnormal fetal heart rate was
      documented in six patients (20%, 95% CI: 6-34). Vaginal bleeding was reported in
      two patients (7%). Only three women had no abnormal abdominal findings after the
      MVC. CONCLUSIONS: From this preliminary series, placental abruption does not
      appear to occur frequently in MVCs with airbag deployment. It is unclear if fetal
      risk is higher than that without airbags. A significant number of pregnant women
      do not wear seatbelts.

PMID- 16967004
TI  - Internal fracture fixation using the Stoppa approach in pelvic ring and
      acetabular fractures: technical aspects and operative results.
AB  - BACKGROUND: The ilioinguinal approach is well established for the treatment of
      pelvic fractures. As an alternative, the modified Stoppa approach can be used to
      expose pelvic and acetabular fractures. We describe our experience with this
      approach in patients with pelvic and acetabular fractures with respect to
      fracture reduction, technical aspects, and the incidence of intra- and
      postoperative complications. METHODS: This retrospective study describes a series
      of 25 consecutive patients where a modified Stoppa approach was used for pelvic
      or acetabular fracture fixation. RESULTS: Fifteen patients with acetabular
      fractures, six patients with a pelvic ring injury not involving the acetabular
      joint and four patients with a combined fracture were operated through a Stoppa
      approach. Nine patients had a total of 13 complications, none of which required
      reoperation. Anatomic or satisfactory reduction was achieved in 95% of the
      acetabular fractures. Pelvic ring fractures had an anatomic (displacement <1 cm)
      postoperative result in all 10 cases. CONCLUSION: The modified Stoppa approach
      allows an adequate exposure and good postoperative results for treatment of
      pelvic ring fractures and acetabular fractures that are eligible for an anterior
      approach.

PMID- 16967005
TI  - A biomechanical comparison of two volar locked plates in a dorsally unstable
      distal radius fracture model.
AB  - BACKGROUND: This study compares the biomechanical stability of two volar locked
      plate systems for fixation of unstable, extra-articular distal radius fractures.
      METHODS: In six matched pairs of fresh frozen cadaveric specimens, a simulated
      unstable, extra-articular distal radius fracture was created. The fractures were
      stabilized with one of two types of volar locked plates. Specimens were axially
      loaded at five different positions: central, volar, dorsal, radial, and ulnar.
      Initial (precyclic loading) stiffness of each locked plate system was calculated.
      Each specimen was then loaded for 5,000 cycles with an 80 N central load.
      Finally, specimens were axially loaded at the same five positions to calculate
      the postcyclic loading stiffness of each volar locked plate system. Main outcome
      measurements were precyclic loading stiffness, postcyclic loading stiffness,
      maintenance of stiffness after cyclic loading, and amount of fracture
      displacement between the two volar locked plate systems. RESULTS: There were no
      differences in maintenance of stiffness and fracture displacement following
      cyclical loading between the two volar plate systems. After cyclic loading, the
      distal volar radius (DVR) locked plate was significantly stiffer than the Synthes
      volar locked plate in volar loading only (p < 0.01). CONCLUSION: Materials
      properties and design differences between these systems did not provide enough
      biomechanical difference to support use of either implant over the other. With
      this in vitro model, both implants provided adequate stability to resist
      physiologic loads expected during therapy in the initial postoperative period.

PMID- 16967006
TI  - Outcome of open release for post-traumatic elbow stiffness.
AB  - BACKGROUND: Post-traumatic elbow stiffness can be caused by a tether and/or a
      block, and these structures can exist both anteriorly and posteriorly about the
      joint to prevent motion. The purpose of this article is to report the outcome of
      elbow release performed for post-traumatic stiffness by a single surgeon.
      METHODS: A retrospective review of charts and radiographs was performed on 52
      case of patients who underwent open surgical treatment for post-traumatic elbow
      contracture by the senior author (RHN). The mean age of the group was 35.1 years.
      There were 32 men and 20 women. Contracture release surgery was performed at an
      average of 14 months from the time of injury. Indication for operative release
      was functional loss of elbow arc of motion that failed nonoperative therapy and
      splinting program. Follow-up was 18.7 months. Comparison of ranges of motion was
      performed with Student's paired t tests. RESULTS: The average extension-flexion
      arc of motion improved from 57 to 116 degrees and forearm rotation improved from
      119 to 145 degrees postoperatively. Fourteen patients (27%) required closed
      manipulation under anesthesia, in the early postoperative period. Five patients
      required a second contracture release at an average of 12 months after the index
      release. Four patients failed because of painful motion (n = 2) and elbow
      instability (n = 2). Other complications included wound infection (n = 3),
      cubital tunnel syndrome (n = 3) and reflex sympathetic dystrophy (n = 1).
      CONCLUSIONS: Open elbow release with excision of tethers and blocks is a valuable
      procedure for post-traumatic stiffness. Recurrence in postoperative period is
      common but is responsive to manipulation under anesthesia and repeat releases.

PMID- 16967007
TI  - Prospective evaluation of a critical care pathway for clearance of the cervical
      spine using the bolster and active range-of-motion flexion/extension techniques.
AB  - BACKGROUND: Clearance of the cervical spine after blunt trauma remains
      controversial in patients with normal radiologic evaluation. METHODS: Blunt
      trauma patients with midline boney cervical tenderness and plain films that
      disclose no abnormalities and computed tomography (CT) scans were entered into a
      care pathway for spinal clearance using the Bolster or active range-of-motion
      (AROM) flexion/extension techniques. The quality of films between the two
      techniques was then compared. RESULTS: In all, 159 patients entered the pathway
      with 14 patients (9%) unable to complete the examination secondary to pain. The
      Bolster was used in 129 patients (89%) and AROM was used in 16 (11%). The total
      range of motion was significantly better with AROM at 51.4 +/- 19.4 degrees of
      motion compared with 32.0 +/- 13.0 degrees with the Bolster (p < or = 0.05). The
      most distal level visualized was not different between groups with 6.6 +/- 0.8
      cervical vertebrae visualized on average in the Bolster group and 6.8 +/- 0.7 in
      the AROM group. Positive findings occurred in five patients (3.4%) in the Bolster
      group. CONCLUSION: The incidence of occult cervical injury in patients with boney
      cervical pain despite normal plain films and CT scans in this study was 3.4%. The
      AROM technique has better total range of motion than the Bolster, although
      results of the Bolster technique remain within acceptable standards. The present
      care pathway appears to be an effective screening tool for evaluation of this
      population of patients. Additional evaluation of the obtunded patient is
      necessary before broad implementation of this technique.

PMID- 16967008
TI  - Risk of thoracolumbar fractures doubled in victims of motor vehicle collisions
      with cervical spine fractures.
AB  - BACKGROUND: An association between cervical fractures and thoracolumbar fractures
      after blunt trauma has long been assumed, but not adequately demonstrated. We
      sought to determine the actual association between these injuries in a large
      nationwide data set. METHODS: The National Trauma Databank (NTDB) was queried for
      victims of blunt vehicular trauma with at least minimal injury. An odds ratio was
      calculated for the association between cervical spine fractures and thoracolumbar
      fractures. RESULTS: Overall 190,183 NTDB patient records met the criteria of a
      motor vehicle crash with more than minimal injury. Of these 7.51% (14,292) had
      cervical spine fractures, 4.73% (8,996) had thoracic spine fractures, 5.93%
      (11,280) had lumbar spine fractures, and 9.79% (18,623) had either thoracic or
      lumbar fractures. Of patients with a cervical spine fracture, 13.06% (2,433) also
      had a thoracic or lumbar fracture, whereas among patients without cervical spine
      fracture only 6.91% (11,859) had a thoracolumbar fracture. The odds ratio (OR)
      for a thoracolumbar fracture in the presence of a cervical spine fracture was
      2.02 (p < 0.0001) (95% confidence interval 1.9318-2.1201). CONCLUSION: These data
      confirm a strong association between cervical spine fractures and thoracolumbar
      fractures after blunt vehicular trauma, and support the practice of imaging the
      complete spine when a cervical fracture is identified.

PMID- 16967009
TI  - Early predictors of long-term work disability after major limb trauma.
AB  - BACKGROUND: A better understanding of the factors influencing return to work
      (RTW) after major limb trauma is essential in reducing the high costs associated
      with these injuries. METHODS: Patients (n = 423) who underwent amputation or
      reconstruction after limb threatening lower extremity trauma and who were working
      before the injury were prospectively evaluated at 3, 6, 12, 24, and 84 months.
      Time to first RTW was assessed. For individuals working at 84 months, the
      percentage of time limited in performance at work was estimated using the Work
      Limitations Questionnaire. RESULTS: Estimates of the cumulative proportion
      returning to work at 3, 6, 12, 24, and 84 months were 0.12, 0.28, 0.42, 0.51, and
      0.58. Patients working at 84 months were, on average, limited in their ability to
      perform the demands of their job 20 to 25% of the time. In the context of a Cox
      proportional hazards model, differences in RTW outcomes by treatment (amputation
      versus reconstruction) were not statistically significant. Factors that were
      significantly associated (p < 0.05) with higher rates of RTW include younger age,
      being White, higher education, being a nonsmoker, average to high self efficacy,
      preinjury job tenure, higher job involvement, and no litigation. Early (3 month)
      assessments of pain and physical functioning were significant predictors of RTW.
      CONCLUSIONS: Return to work after severe lower extremity trauma remains a
      challenge. Although the causal pathway from injury to impairment and work
      disability is complex, this study points to several factors that influence RTW
      that suggest strategies for intervention.

PMID- 16967010
TI  - Incidence and propagation of infrageniculate deep venous thrombosis in trauma
      patients.
AB  - BACKGROUND: The incidence and propagation of thrombosis involving vessels distal
      to the popliteal vein has not been clearly defined in trauma patients. Our aim
      was to determine the incidence and rate of propagation of infrageniculate deep
      venous thrombosis (DVT) in a trauma population and identify potential risk
      factors specific to propagation. METHODS: Retrospective review of all trauma
      admissions between the years 2001 and 2003 was conducted. Only those 18 years or
      older with an isolated infrageniculate DVT who underwent a lower extremity venous
      duplex scan during admission were included in the study. Nature of injury, injury
      severity score (ISS), method of DVT prophylaxis, thrombus location, and risk
      factors for hypercoagulable states were recorded. RESULTS: During the study
      period, 698 trauma admissions were included, and 109 (15.7%) with infrageniculate
      DVT were identified. Thirty-nine (35.7%) had thrombus propagation (14
      suprageniculate and 25 infrageniculate) with a mean ISS of 27.6. Seventy (64.3%)
      had infrageniculate DVT without propagation and a mean ISS of 19.6. Thirty-eight
      (97%) patients with propagating infrageniculate DVT had received mechanical
      prophylaxis, and 33 (84%) also received chemical prophylaxis. The 14 patients
      with suprageniculate thrombus propagation were the most severely injured (mean
      ISS = 35.1). Elevated ISS, operation, age < or =62 years, and intensive care unit
      admission were positively correlated with propagation of infrageniculate DVT.
      CONCLUSION: The incidence and propagation of infrageniculate DVT in an
      aggressively prophylaxed trauma population are greater than previously reported.
      The clinical significance of isolated infrageniculate DVT remains to be
      determined, but when associated with a multiple injury trauma, the patient may be
      at risk for future suprageniculate DVT formation and may benefit from therapeutic
      anticoagulation.

PMID- 16967011
TI  - A new approach to outcome prediction in trauma: A comparison with the TRISS
      model.
AB  - BACKGROUND: The Trauma Audit & Research Network (TARN) has been using the TRISS
      methodology since 1989. Its database contains 200,000 hospital admissions from
      110 hospitals over the country. To improve outcome prediction, a revision of the
      current model became necessary. Our model tried to overcome some of the concerns
      of the trauma community, namely missing data, functional form of the predictors,
      inclusion criteria and patient's death within 30 days. METHODS: The data for
      modeling consisted of 100,399 anonymized hospital trauma admissions during the
      period 1996 to 2001. Cross validation was performed on this data set, and a
      multiple logistic regression model was derived using the prediction set and then
      its prediction ability was tested on the validation set. Fractional polynomials
      modeling showed that the linear functional form of the Injury Severity Score
      (ISS) in the model was not satisfactory. Using the Glasgow Coma Score (GCS)
      instead of the revised trauma score (RTS) has dramatically reduced the number of
      missing cases. Sex and its interaction with age have also been included in the
      model. The model was tested on different subsets of cases, traditionally
      excluded, such as children, those with penetrating injuries, and ventilated and
      transferred patients. The new model included all those subsets using age, a
      transformation of ISS, GCS, sex, and sex by age interaction as predictors.
      RESULTS: The model has shown a good discriminant ability tested by the Area under
      the Receiver Operating Characteristic (AROC) curve. The values of the AROC for
      the new model were 0.947 (95% confidence interval [CI]: 0.943-0.951) on the
      prediction set and 0.952 (95% CI: 0.946-0.957) on the validation set compared,
      respectively, with 0.937 (95% CI: 0.932-0.943) and 0.941 (95% CI: 0.936-0.952)
      for TRISS. CONCLUSION: The new model has enabled us to include most of the cases
      that were excluded under the TRISSs inclusion criteria, less missing data are
      incurred and the predictive performance was significantly better than that of the
      TRISS model as shown by the AROC curves.

PMID- 16967012
TI  - Different AIS triplets: Different mortality predictions in identical ISS and
      NISS.
AB  - BACKGROUND: Previous studies demonstrated different mortality predictions for
      identical Injury Severity Scores (ISS) from different Abbreviated Injury Scale
      (AIS) triplets. This study elaborates in both scope and volume producing results
      of a larger magnitude, applicable to specific injury subgroups of blunt or
      penetrating, traumatic brain injury, various age groups, and replicated on NISS.
      METHODS: All patients hospitalized after trauma at 10 hospitals, with ISS/NISS
      (new ISS) generated by two AIS triplets, excluding patients with isolated minor
      or moderate injuries to a single body region were studied. Patients were
      separated into two groups based on the different triplets. Inpatient-mortality
      rates were calculated for each triplet group. Odds ratios were calculated to
      estimate the risk of dying in one triplet group as compared with the other. The
      chi test determined whether the difference in mortality rate between the two
      groups was significantly different. Differences were further explored for various
      subgroups. RESULTS: There were 35,827 patients who had ISS/NISS scores generated
      by two different AIS triplets. Significant differences in death rates were noted
      between triplet groups forming identical ISS/NISS. Odds ratio for being in the
      second group (always containing the higher AIS score) ranged from 2.3 to 7.4.
      CONCLUSIONS: ISS and NISS that are formed by different AIS triplets have
      significantly different inpatient-mortality rates. The triplet with the higher
      AIS score has higher inpatient-mortality rates, overall and in several sub
      populations of varying vulnerability. The comparison of populations and the
      interpretation of ISS/NISS based outcome data should take this important
      information into account and the components of AIS triplets creating each ISS and
      NISS should be reported.

PMID- 16967013
TI  - Unification of the revised trauma score.
AB  - BACKGROUND: The Revised Trauma Score (RTS) calculated with Major Outcome Trauma
      Study weights (MTOS-RTS) is currently the standard physiologic severity score in
      trauma research and quality control. It is often confused with the Triage-RTS (T
      RTS), a version that is easier to calculate but only intended for clinical
      triage. OBJECTIVES: To compare the accuracy of the MTOS-RTS to the RTS calculated
      with weights derived from the study population (POP-RTS) and the T-RTS, for
      predicting mortality in a trauma population. METHODS: The study population
      consists of 22,388 patients, drawn from the trauma registries of three Level I
      trauma centers. The predictive accuracy of the MTOS-RTS, POP-RTS, and the T-RTS
      were compared using measures of discrimination and model fit from logistic
      regression models. RESULTS: The MTOS-RTS, the POP-RTS, and the T-RTS had the same
      discrimination (Area under the Receiver Operating Curve [AUC] = 0.841). The POP
      RTS and the T-RTS had a slightly better model fit than the MTOS-RTS (AIC = 8010,
      8010, and 8067, respectively). The T-RTS had equal discrimination and equal or
      better model fit than the MTOS-RTS in the whole sample, in each of the three
      trauma centers and in the population of patients with severe head trauma. The T
      RTS was also equivalent to the POP-RTS in all of these population sub-groups.
      CONCLUSIONS: The T-RTS could replace the MTOS-RTS as the standard physiologic
      severity score for trauma outcome prediction. The advantages of using the T-RTS
      over the MTOS-RTS are ease of calculation, the need for only one measure for
      triage and mortality prediction purposes and universal adaptation to a broad
      range of trauma populations.

PMID- 16967014
TI  - Pilot study on the comprehensive economic costs of major trauma: Consequential
      costs are well in excess of medical costs.
AB  - BACKGROUND: Trauma care is expensive. However, reliable data on the exact
      lifelong costs incurred by a major trauma patient are lacking. Discussion usually
      focuses on direct medical costs--underestimating consequential costs resulting
      from absence from work and permanent disability. METHODS: Direct medical costs
      and consequential costs of 63 major trauma survivors (ISS >13) at a Swiss trauma
      center from 1995 to 1996 were assessed 5 years posttrauma. The following cost
      evaluation methods were used: correction cost method (direct cost of restoring an
      original state), human capital method (indirect cost of lost productivity),
      contingent valuation method (human cost as the lost quality of life), and
      macroeconomic estimates. RESULTS: Mean ISS (Injury Severity Score) was 26.8 +/-
      9.5 (mean +/- SD). In all, 22 patients (35%) were disabled, causing discounted
      average lifelong total costs of USD 1,293,800, compared with 41 patients (65%)
      who recovered without any disabilities with incurred costs of USD 147,200
      (average of both groups USD 547,800). Two thirds of these costs were attributable
      to a loss of production whereas only one third was a result of the cost of
      correction. Primary hospital treatment (USD 27,800 +/- 37,800) was only a minor
      fraction of the total cost--less than the estimated cost of police and the
      judiciary. Loss of quality of life led to considerable intangible human costs
      similar to real costs. CONCLUSIONS: Trauma costs are commonly underestimated.
      Direct medical costs make up only a small part of the total costs. Consequential
      costs, such as lost productivity, are well in excess of the usual medical costs.
      Mere cost averages give a false estimate of the costs incurred by patients
      with/without disabilities.

PMID- 16967015
TI  - Use of ipsilateral superficial femoral vein for common femoral vein
      reconstruction after trauma: A useful approach in selected cases.

PMID- 16967016
TI  - Two-stage reconstruction of the superior vena cava after gunshot to the chest.

PMID- 16967017
TI  - Modified rapid deployment hemostat terminates bleeding from hepatic rupture in
      third trimester.

PMID- 16967018
TI  - Pericardial tamponade with a positive abdominal FAST scan in blunt chest trauma.

PMID- 16967019
TI  - Delayed massive pleural effusion after scoliosis correction and thoracoplasty: A
      case report.

PMID- 16967020
TI  - Degloving injury of pelvis treated by internal fixation and omental flap
      reconstruction.

PMID- 16967021
TI  - Trans-orbital foreign body with intracranial extension.

PMID- 16967022
TI  - The wire-guided endobronchial blocker: Applications in trauma patients beyond
      mere single-lung ventilation.

PMID- 16967023
TI  - Tyrolean tensiometer: A new instrument for easy intraoperative tension
      measurement before nerve coaptation.
AB  - BACKGROUND: In reconstructive surgery microsurgical repair of dissected nerves
      can be done end-to-end or by using a nerve graft. Guidelines to support an
      objective decision, whether tension associated with direct suture is acceptable
      or grafting is needed, do not exist. All experimental data found concerned the
      clinical outcome when a certain length defect was treated in various animal
      models. The aim of this study was to show the feasibility of a new instrument for
      measuring the tension needed to coapt nerve stumps before beginning nerve suture.
      METHODS: A tension spring balance was modified in a way that the thread of the
      first suture is used to measure the force applied to the two nerve stumps by the
      suture before knotting. Immediately after measuring, the suture can be completed
      by knotting. Twenty-four rat sciatic nerves were dissected, segments of various
      length were resected, and tension needed for approximation was measured. These ex
      vivo data were combined with clinical outcome data of previous animal trials.
      RESULTS: Data obtained showed that tension measured increased almost
      proportionally to the size of the gap created. The average additional time needed
      to measure the tension using the Tyrolean Tensiometer was 11 (+/-4) seconds.
      CONCLUSIONS: None of the methods described before allow intraoperative tension
      measurement at a time when changes in strategy are still possible. The Tyrolean
      Tensiometer allows fast and reliable measurement of the tension acting on the
      first suture and might hereby be useful in predicting final operative outcome.

PMID- 16967024
TI  - Serial computed tomographic scans document healing of solid organ injury in a
      trauma patient with multiple injuries.

PMID- 16967025
TI  - Abdominal wall injury perpetrated by a shark.

PMID- 16967026
TI  - Majority of the 50 states lack effective trauma systems.

PMID- 16967027
TI  - A typical bird flu infection, caused by the H5N1 virus, is a new emerging
      infectious disease.

PMID- 16967028
TI  - Injuries are growing public health concern in low- and middle-income countries
      (LMICs).

PMID- 16967029
TI  - Evaluating the influence of focused assessment sonography for trauma (FAST) on
      individual patient management in a major trauma center.

PMID- 16967031
TI  - Fibular osteosarcomas: contaminated margins may not impact survival.
AB  - The fibula is an expendable bone which when affected by primary malignancy may
      simplify treatment and improve outcome. This concept was questioned previously in
      a study showing a high rate of inadequate margins at surgical resection. We asked
      whether margin status and other dependent variables affect survival. We analyzed
      the charts of 36 patients with fibular osteosarcomas treated from 1919 to 2000.
      We estimated survival by the Kaplan-Meier method and the prognostic significance
      of dependent variables, especially marginal status, with univariate association
      using Cox proportional hazard regression. The survival of patients with fibular
      osteosarcomas was limited, with a median survival of 5 years 4 months after
      diagnosis. At 5 years, 16 patients died of their disease. Sixteen patients were
      still alive at 10 years followup. The margin status at surgery was not associated
      with survival. A higher tumor grade at diagnosis, surgical treatment with above
      knee amputation, and occurrence of metastasis were associated with poorer long
      term survival. The survival of patients with fibular osteosarcomas was not better
      than with osteosarcomas arising in other locations. A marginal resection
      surprisingly did not impact on overall survival, although we had a limited
      dataset and heterogeneous treatment protocols.

PMID- 16967032
TI  - Recurrent fracture after operative treatment for a tibial stress fracture.
AB  - We report a patient with a recurrent stress fracture and subsequent nonunion
      around an intramedullary nail placed for treatment of a more proximal, chronic
      tibial stress fracture. After 9 months of failed nonoperative treatment, we
      performed an exchange intramedullary nailing with open bone graft. At 8 months
      postoperatively, the patient showed clinical and radiographic signs of healing.

PMID- 16967033
TI  - A hydroxyapatite graft substitute reduces subsidence in a femoral impaction
      grafting model.
AB  - Synthetic bone graft substitutes have been developed for impaction grafting
      revision hip surgery in response to concerns about the availability and potential
      infection risk of allograft. We performed an in vitro experiment to determine
      whether a synthetic porous hydroxyapatite material might improve resistance to
      cumulative subsidence and cyclic (elastic) movement on loading. We impacted
      different ratios of hydroxyapatite and allograft (0%, 50%, 70%, and 90%
      hydroxyapatite) into composite femoral models (eight per group) and implanted
      tapered, polished stems with cement. Models were loaded for 18,000 cycles on a
      servohydraulic materials testing machine. Migration of the femoral prostheses and
      the distal cement was determined using radiostereometric analysis, and cyclic
      movement was measured mechanically by the testing machine. Hydroxyapatite
      decreased overall subsidence and subsidence at the prosthesis-cement interface,
      but there was no difference at the cement-femur interface. This decrease may have
      occurred because the hydroxyapatite-containing graft was more rigid, or because
      it resulted in a thicker cement mantle. Cyclic prosthesis movement also was lower
      with hydroxyapatite. While the biologic response to porous hydroxyapatite remains
      to be determined, its mechanical properties appear promising.

PMID- 16967034
TI  - Intramedullary fixation of tibial shaft fractures using an expandable nail.
AB  - Interlocking intramedullary nails are the gold standard for treating tibial
      fractures. We compared the clinical and economic factors associated with tibial
      fracture fixation using either interlocking intramedullary or expandable nails.
      From 2000 to 2002, 53 patients with 53 diaphyseal tibial fractures of similar
      characteristics (AO/OTA 42A1-B3) were randomly and prospectively treated with
      either interlocking (n = 26) or expandable nails (n = 27). Patients were followed
      for a minimum of 2 years. The mean surgical duration was 104 minutes with
      interlocking nails and 52.9 minutes with expandable nails. Rehospitalizations
      were required in 12 patients (46%) and reoperations were required in nine
      patients (35%) with interlocking nails. Only one patient (3%) with an expandable
      nail required rehospitalization and reoperation. Union was achieved after 17
      weeks (mean) with interlocking nails and 11.5 weeks with expandable nails. The
      beneficial economic ramifications of using expandable nails were a 39% reduction
      in overall surgical and hospital expenses. Expandable nails showed important
      clinical advantages for tibial fracture fixation, and complications related to
      lengthy operations, reoperations, and rehospitalizations were substantially
      reduced. Overall treatment cost was substantially lower with expandable nails.
      Based on these advantages, simplicity in use, and short surgical time, we
      recommend an expandable nail for treating tibial (AO Type A, B) shaft fractures.

PMID- 16967035
TI  - The John Insall Award: Patient expectations affect satisfaction with total knee
      arthroplasty.
AB  - Satisfaction with the outcome of total knee arthroplasty is highly variable, with
      a small but significant percentage of patients reporting dissatisfaction with the
      procedure. The purpose of this study was to determine which factors contribute to
      patient satisfaction with total knee replacement (TKR), and their relative
      importance. At a minimum of 1 year post unilateral primary TKR, 253 patients
      completed a self-administered, validated "Knee Function Questionnaire," which
      examined each patient's participation in a broad range of activities involving
      the knee, their level of satisfaction, and the extent to which TKR had fulfilled
      their expectations. The association between function, expectation and
      satisfaction was examined using univariate and multivariate logistic regression.
      Seventy-five percent of patients were either "satisfied" or "very satisfied" with
      their knee replacement, while 14% were "dissatisfied" or "very dissatisfied."
      Satisfaction correlated significantly (p < 0.001) with age less than 60, absence
      of residual symptoms, fulfillment of expectations, and absence of functional
      impairment. Satisfaction with TKR is primarily determined by patients'
      expectations, and not their absolute level of function. Real improvements in the
      outcome of TKA must address prevention of residual pain, stiffness and swelling,
      and each patient's preoperative concept of the likely outcome of these
      procedures.

PMID- 16967036
TI  - Minimally invasive total knee arthroplasty: the mini midvastus approach.
AB  - Minimally invasive knee surgery offers the potential for earlier return of
      motion. To ascertain whether this potential is realized we retrospectively
      reviewed 335 consecutive patients (391 knees) who underwent minimally invasive
      total knee arthroplasties from September 2001 to September 2004 using the mini
      midvastus approach. There were 248 women and 87 men, with an average preoperative
      range of motion (ROM) of 109 degrees. Sixty-three percent of patients had a body
      mass index of less than 30% and 33% had a body mass index from 30 to 39. Patients
      received epidural anesthesia and a posterior-stabilized knee. We obtained Knee
      Society scores and determined ROM. The mean ROM at 6 weeks postoperatively was
      111 degrees, 121 degrees at 3 months, and 125 degrees at 1 year and 2 years
      postoperatively. Knee Society scores were 95 or over at all followup periods.
      Postoperative ROM was related to preoperative ROM, although patients with less
      preoperative motion had the greatest improvements at 6 weeks and 3 months
      postoperatively. We observed no increased complication rate with this approach.
      Minimally invasive total knee arthroplasty with a mini midvastus approach was
      associated with rapid functional recovery and substantial improvements in ROM.
      This procedure can be performed safely and provides high Knee Society scores
      short term.

PMID- 16967037
TI  - Internet promotion of MIS and CAOS in TKA By Knee Society members.
AB  - Minimally invasive surgery (MIS) and computer-assisted orthopaedic surgery (CAOS)
      options for total knee arthroplasty (TKA) have become increasingly popular.
      However, few controlled studies document their efficacy and safety. We examined
      the Internet for Knee Society members' websites to evaluate the level of
      promotion for these procedures in terms of direct (surgeon endorsed) and indirect
      (surgeon associated) information. On 92 websites, 22.7% made indirect reference
      to MIS TKA, while only 10.9% made a direct reference. Of the sites referencing
      MIS TKA, faster recovery was reported on 90% of indirect sites and 50% of direct
      sites. Specific risks were discussed on only 35% of indirect sites, and on only
      20% of direct sites. CAOS TKA was discussed on 6.5% of indirect sites and on 5.4%
      of direct sites. Although MIS and CAOS TKA are frequently discussed on the
      Internet, only a small percentage of KS members directly promote these techniques
      (10.9% and 5.4%, respectively). Information was often indirectly associated with
      KS surgeons through institutional websites or hospital affiliations. Information
      indirectly associated with a surgeon may be mistaken as endorsing the procedure
      by a prospective patient.

PMID- 16967038
TI  - Extensor mechanism allograft reconstruction in TKA at a mean of 56 months.
AB  - Extensor mechanism disruption in total knee arthroplasty (TKA) occurs
      infrequently but often requires surgical intervention. We compared two cohorts
      undergoing extensor mechanism allograft reconstruction and presumed both types of
      extensor mechanism allograft reconstruction will be successful but for different
      indications and forms of extensor failure. Nineteen consecutive patients with
      extensor mechanism disruption after TKA were treated. Two different types of
      extensor mechanism allografts were used: quadriceps tendon-patella-patella tendon
      tibial tubercle, and Achilles tendon allograft. Demographic factors, diagnosis at
      extensor failure, Knee Society clinical rating scores, radiographs, and patient
      satisfaction were recorded. The average time from extensor mechanism disruption
      to surgery was 6.6 months (range, 1-24 months). At a mean followup of 56 months
      (range, 24-96 months), all patients were community ambulators. The mean Knee
      Society score improved from 27 points preoperatively to 76 points
      postoperatively. There was no loss of knee flexion postoperatively. The mean
      postoperative lag was 14 degrees. Fifteen patients had an extensor lag of less
      than 10 degrees. All patients thought their functional status had improved, and
      89% were satisfied with the results of the allograft reconstruction. The total
      extensor mechanism allograft and Achilles tendon allograft both were successful
      in the treatment of the failed extensor mechanism.

PMID- 16967039
TI  - Revision of the polyethylene component for wear in TKA.
AB  - Given reports of failure in isolated polyethylene exchange in well-fixed TKA
      components, we asked whether isolated exchange could be successful either by
      replacing the polyethylene in implants whose locking mechanism accepts currently
      available polyethylene designs or by creating a new locking mechanism fabricated
      with a carbide bit and augmented with polymethylmethacrylate cement. We performed
      isolated liner exchange for wear in 46 patients (49 knees). The polyethylene
      locking mechanism in two total knee designs (13 knees) allowed polyethylene
      exchange without polymethylmethacrylate fixation. A locking mechanism was
      fabricated for three implant designs (36 knees). Clinical function after
      polyethylene component exchange was good in all but three knees. No knees with a
      fabricated locking mechanism failed. The mechanical strength of the fabricated
      locking mechanism was tested in the laboratory. The cement- fabricated locking
      mechanism in the unmodified tray notably outperformed the standard polyethylene
      locking mechanism. Isolated polyethylene component exchange was successful in
      this small clinical study. Fabricating a locking mechanism with a carbide bit and
      acrylic cement was effective in laboratory testing and clinical application.

PMID- 16967040
TI  - Long-term results of initial therapy with abacavir and Lamivudine combined with
      Efavirenz, Amprenavir/Ritonavir, or Stavudine.
AB  - OBJECTIVE: To compare alternative class-sparing antiretroviral regimens in
      treatment-naive subjects. DESIGN: Open-label, multicenter, randomized trial of up
      to 3 consecutive treatment regimens over 96 weeks. METHODS: Two hundred ninety
      one subjects received abacavir (ABC) and lamivudine and efavirenz (nonnucleoside
      reverse transcriptase inhibitors [NNRTIs]), ritonavir-boosted amprenavir
      (protease inhibitor [PI]), or stavudine (nucleoside reverse transcriptase
      inhibitor [NRTI]) by random assignment. The primary end points were the
      percentages of subjects with plasma HIV-1 RNA levels <400 copies/mL and time to
      treatment failure over 96 weeks. RESULTS: Ninety percent of subjects completed 96
      weeks of follow-up, and 79% remained on study treatment. At week 96, there were
      no differences between arms in the percentages of subjects with plasma HIV-1 RNA
      levels <400 and <50 copies/mL, mean changes in plasma HIV-1 RNA levels, time to
      treatment failure, time to first or second virologic failure, or CD4 cell counts.
      The NNRTI arm had a greater percentages of subjects with RNA levels <or=50
      copies/mL at weeks 24 and 48 and a greater overall duration of plasma HIV-1 RNA
      levels <400 copies/mL. Three subjects in the NNRTI arm had treatment failure on
      their first regimen and switched therapy compared with 16 in the NRTI arm and 13
      in the PI arm. Twenty-one subjects had hypersensitivity reactions attributed to
      ABC (7.3%). Fewer drugs were used by subjects in the NNRTI arm, and fewer
      subjects in the NNRTI arm used 3 drug classes. CONCLUSIONS: All treatment
      regimens demonstrated excellent 96-week results. Secondary analyses favored the
      NNRTI regimen over the PI and NRTI regimens.

PMID- 16967041
TI  - Predictors of antiretroviral-related hepatotoxicity in the adult AIDS Clinical
      Trial Group (1989-1999).
AB  - HIV antiretroviral therapy (ART)-related hepatotoxicity is a significant clinical
      problem, resulting in severe elevations of liver enzymes and, potentially, liver
      failure and death. We retrospectively determined baseline clinical predictors of
      severe hepatotoxicity (SH; serum aminotransferases or total bilirubin >5 times
      and >2.5 times the upper limit of normal [ULN], respectively) among 8,851
      subjects enrolled in 16 Adult AIDS Clinical Trial Group studies from October 1989
      to June 1999. Subjects were divided into the following treatment categories:
      single nucleoside reverse transcriptase inhibitors (NRTIs), multiple NRTIs,
      nonnucleoside reverse transcriptase inhibitors (NNRTIs) combined with NRTIs, and
      the protease inhibitor (PI) indinavir (IDV) combined with NRTIs. SH occurred in
      824 (9.3%) subjects, in 613 (6.92%) in the first 6 months and in another
      211(2.38%) in the subsequent 6 months of study ART. Consistent with other
      reports, baseline elevation in serum aminotransferases was a significant risk
      factor for SH for all regimens. Risk factors not previously identified included
      concomitant hepatotoxic medications, thrombocytopenia, and renal insufficiency.
      Hepatitis C virus coinfection was associated with an increased risk of SH (odds
      ratio [OR] = 2.7; P < 0.003). In conclusion, this study identified known and
      previously unreported risk factors for severe hepatotoxicity that should be
      considered before the initiation of ART.

PMID- 16967042
TI  - Effects of highly active antiretroviral therapy and immune recovery on CD8+ T
      cell-mediated inhibition of HIV-1 transcription.
AB  - SUMMARY: : To date, the relation between the CD8 antiviral factor (CAF) and
      clinical indicators of disease progression in HIV-1 infection (CD4 T-cell counts
      and viral load [VL]) is inconclusive. Particularly, the effect of antiretroviral
      therapy and immune recovery on CAF production remains unclear. Using a transient
      transfection assay and a reporter gene activated by the HIV-1 long terminal
      repeat (LTR), we analyzed CAF production in CD8 T cells of HIV-1-positive
      individuals divided into 3 groups: patients on protease inhibitor (PI)-based
      therapy, patients on nonnucleoside reverse transcriptase inhibitor (NNRTI)-based
      therapy, and patients receiving no therapy. We found that within the untreated
      group, CAF activity inversely correlated with VL and high CAF was associated with
      lower VLs over a period of 0.5 to 3 years. Furthermore, patients who were drug
      naive demonstrated significantly higher CAF than untreated patients who had
      previously undergone antiretroviral therapy. CAF activity in treated patients was
      similar to CAF in drug-naive patients and higher than in off-treatment patients.
      There seemed to be a trend toward higher CAF in patients on NNRTI-based therapy
      compared with those on PI-based therapy. These results suggest that immune
      recovery after highly active antiretroviral therapy (HAART) contributes to the
      normalization of CAF levels in HIV-1-positive individuals. Furthermore, we have
      distinguished between CD8 T-cell-mediated suppression of HIV-1 replication and
      gene transcription.

PMID- 16967043
TI  - Highly active antiretroviral therapy attenuates re-endothelialization and alters
      neointima formation in the rat carotid artery after balloon injury.
AB  - Highly active antiretroviral therapy (HAART) has led to a sustained decline of
      HIV-associated morbidity and mortality. HAART exhibits significant side effects,
      however, such as hyperlipidemia and hyperglycemia, which possibly contribute to
      accelerated atherosclerosis in HAART-treated patients. In addition, direct
      effects of HAART on vascular cells have been described, which may promote
      atherosclerotic lesion formation. The effects of HAART on balloon-induced
      neointima formation have not been studied previously. The rat carotid artery
      balloon model was used to evaluate the effects of HAART (lopinavir, ritonavir,
      lamivudine, and zidovudine) on neointima formation and endothelial recovery.
      Furthermore, the effects of concomitant administration of the 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor rosuvastatin were
      investigated. HAART-treated animals displayed an increase in lesion size
      (neointima/media ratio: 1.14 +/- 0.32 vs. 1.31 +/- 0.20 in control vs. HAART; P <
      0.05) and an impaired regenerative capacity of the endothelium, as indicated by
      reduction in endothelial regrowth from an adjacent undilated vessel segment 14
      days after injury (re-endothelialization area: 8.29 +/- 1.45 mm vs. 5.09 +/- 0.53
      mm in control vs. HAART; P < 0.05). When rosuvastatin was given in addition to
      HAART, these effects were not observed. In conclusion, HAART inhibited
      endothelial cell-mediated healing and promoted neointima formation after
      angioplasty in rats. These deleterious effects were attenuated by cotreatment
      with rosuvastatin, however. Our studies suggest that currently used drug regimens
      against HIV infection may lead to an increased risk for restenosis after
      percutaneous vascular interventions. Moreover, the findings indicate that the
      additional treatment with statins might counteract these adverse effects by
      HAART.

PMID- 16967044
TI  - Interleukin-7 receptor expression on CD8 T-cells is downregulated by the HIV Tat
      protein.
AB  - We have previously shown decreased expression of the interleukin (IL)-7 receptor
      alpha-chain (CD127) on CD8 T-cells in HIV-infected patients and an apparent
      recovery of this receptor in those receiving antiretroviral therapy with
      sustained viral suppression. Here, we demonstrate that the HIV Tat protein
      specifically downregulates cell surface expression of CD127 on human CD8 T-cells
      in a dose- and time-dependent manner. The effects of Tat on CD127 expression
      could be blocked with anti-Tat monoclonal antibodies or by preincubating Tat with
      heparin. Tat had no effect on the expression of other cell surface proteins
      examined, including CD132, or on cell viability over 72 hours. Further, CD127
      expression was not altered by other HIV proteins, including gp160 or Nef.
      Preincubation of purified CD8 T-cells with Tat protein inhibited CD8 T-cell
      proliferation and perforin synthesis after stimulation with IL-7. Because IL-7
      signaling is essential for optimal CD8 T-cell proliferation and function, the
      downregulation of CD127 and apparent inhibition of cytotoxic activity by Tat may
      play an important role in HIV-induced immune dysregulation and impaired cell
      mediated immunity.

PMID- 16967045
TI  - Treatment of allergic rhinitis can improve blood pressure control.
AB  - Owing to high prevalence of arterial hypertension (AH) and allergic rhinitis
      (AR), these diseases frequently coexist. The study aimed to assess whether
      improvement of AR by conventional treatment can improve blood pressure (BP)
      control in this population. Sixty-eight subjects of both sexes aged 35-60 years
      with AR and AH were randomized into two groups to receive in addition to their
      antihypertensive medications: treatment group (n=34) Fluticasone nasal 50
      microg/spray b.i.d. and Fenoxifenadine 180 mg tablets q.d., and control group
      (n=34) 0.9% NaCl nasal drops b.i.d. Office BP and AR severity (using the Relative
      Quality of Life Questionnaire (RQLQ)) and high-sensitive C-reactive protein (hs
      CRP) were measured at study entry and after 8 weeks in both groups, without
      changing of antihypertensive medications. In Treatment group an improvement in
      RQLQ, significant reduction of systolic BP (SBP) (DSBP 7.4 +/- 4.3 mm Hg,
      P=0.006) and reduction of hs-CRP level (DCRP 2.05 +/- 1.08; P=0.028) were
      observed, whereas diastolic BP (DBP) remained unchanged (DDBP 0.9 +/- 1.7 mm Hg,
      P=0.7). There was a significant correlation between DRQLQ and DSBP (r=0.86;
      P=0.019) and between DCRP and DSBP (r=0.56; P=0.027). No statistically
      significant changes of RQLQ, BP and CRP were observed in the control group. In
      patients with coincidence of AH and AR, medications meant to improve AR attenuate
      low-grade systemic inflammation and can lower SBP, but not DBP.

PMID- 16967046
TI  - Drug-induced long QT syndrome: hERG K+ channel block and disruption of protein
      trafficking by fluoxetine and norfluoxetine.
AB  - BACKGROUND AND PURPOSE: Fluoxetine (Prozac) is a widely prescribed drug in adults
      and children, and it has an active metabolite, norfluoxetine, with a prolonged
      elimination time. Although uncommon, Prozac causes QT interval prolongation and
      arrhythmias; a patient who took an overdose of Prozac exhibited a prolonged QT
      interval (QTc 625 msec). We looked for possible mechanisms underlying this
      clinical finding by analysing the effects of fluoxetine and norfluoxetine on ion
      channels in vitro. EXPERIMENTAL APPROACH: We studied the effects of fluoxetine
      and norfluoxetine on the electrophysiology and cellular trafficking of hERG K+
      and SCN5A Na+ channels heterologously expressed in HEK293 cells. KEY RESULTS:
      Voltage clamp analyses employing square pulse or ventricular action potential
      waveform protocols showed that fluoxetine and norfluoxetine caused direct,
      concentration-dependent, block of hERG current (IhERG). Biochemical studies
      showed that both compounds also caused concentration-dependent reductions in the
      trafficking of hERG channel protein into the cell surface membrane. Fluoxetine
      had no effect on SCN5A channel or HEK293 cell endogenous current. Mutations in
      the hERG channel drug binding domain reduced fluoxetine block of IhERG but did
      not alter fluoxetine's effect on hERG channel protein trafficking. CONCLUSIONS
      AND IMPLICATIONS: Our findings show that both fluoxetine and norfluoxetine at
      similar concentrations selectively reduce IhERG by two mechanisms, (1) direct
      channel block, and (2) indirectly by disrupting channel protein trafficking.
      These two effects are not mediated by a single drug binding site. Our findings
      add complexity to understanding the mechanisms that cause drug-induced long QT
      syndrome.

PMID- 16967047
TI  - Combined hERG channel inhibition and disruption of trafficking in drug-induced
      long QT syndrome by fluoxetine: a case-study in cardiac safety pharmacology.
AB  - Drug-induced prolongation of the rate-corrected QT interval (QTCI) on the
      electrocardiogram occurs as an unwanted effect of diverse clinical and
      investigational drugs and carries a risk of potentially fatal cardiac
      arrhythmias. hERG (human ether-a-go-go-related gene) is the gene encoding the
      alpha-subunit of channels mediating the rapid delayed rectifier K+ current, which
      plays a vital role in repolarising the ventricles of the heart. Most QTCI
      prolonging drugs can inhibit the function of recombinant hERG K+ channels,
      consequently in vitro hERG assays are used widely as front-line screens in
      cardiac safety-testing of novel chemical entities. In this issue, Rajamani and
      colleagues report a case of QTCI prolongation with the antidepressant fluoxetine
      and correlate this with a dual effect of the drug and of its major metabolite
      norfluoxetine on hERG channels. Both compounds were found to produce an acute
      inhibition of the hERG channel by pharmacological blockade, but in addition they
      also were able to disrupt the normal trafficking of hERG protein to the cell
      membrane. Mutations to a key component of the drug binding site in the S6 region
      of the channel greatly attenuated channel block, but did not impair disruption of
      trafficking; this suggests that channel block and drug effects on trafficking
      were mediated by different mechanisms. These findings add to growing evidence for
      disruption of hERG channel trafficking as a mechanism for drug-induced long QT
      syndrome and raise questions as to possible limitations of acute screening
      methods in the assessment of QTcI prolonging liability of drugs in development.

PMID- 16967048
TI  - Combination of Ca2+ -activated K+ channel blockers inhibits acetylcholine-evoked
      nitric oxide release in rat superior mesenteric artery.
AB  - BACKGROUND AND PURPOSE: The present study investigated whether calcium-activated
      K+ channels are involved in acetylcholine-evoked nitric oxide (NO) release and
      relaxation. EXPERIMENTAL APPROACH: Simultaneous measurements of NO concentration
      and relaxation were performed in rat superior mesenteric artery and endothelial
      cell membrane potential and intracellular calcium ([Ca2+]i) were measured. KEY
      RESULTS: A combination of apamin plus charybotoxin, which are, respectively,
      blockers of small-conductance and of intermediate- and large-conductance Ca2+ 
      activated K channels abolished acetylcholine (10 microM)-evoked hyperpolarization
      of endothelial cell membrane potential. Acetylcholine-evoked NO release was
      reduced by 68% in high K+ (80 mM) and by 85% in the presence of apamin plus
      charybdotoxin. In noradrenaline-contracted arteries, asymmetric dimethylarginine
      (ADMA), an inhibitor of NO synthase inhibited acetylcholine-evoked NO release and
      relaxation. However, only further addition of oxyhaemoglobin or apamin plus
      charybdotoxin eliminated the residual acetylcholine-evoked NO release and
      relaxation. Removal of extracellular calcium or an inhibitor of calcium influx
      channels, SKF96365, abolished acetylcholine-evoked increase in NO concentration
      and [Ca2+]i. Cyclopiazonic acid (CPA, 30 microM), an inhibitor of sarcoplasmic
      Ca2+ -ATPase, caused a sustained NO release in the presence, but only a transient
      increase in the absence, of extracellular calcium. Incubation with apamin and
      charybdotoxin did not change acetylcholine or CPA-induced increases in [Ca2+]i,
      but inhibited the sustained NO release induced by CPA. CONCLUSIONS AND
      IMPLICATIONS: Acetylcholine increases endothelial cell [Ca2+]i by release of
      stored calcium and calcium influx resulting in activation of apamin and
      charybdotoxin-sensitive K channels, hyperpolarization and release of NO in the
      rat superior mesenteric artery.

PMID- 16967049
TI  - The C-terminus of murine S100A9 protein inhibits hyperalgesia induced by the
      agonist peptide of protease-activated receptor 2 (PAR2).
AB  - BACKGROUND AND PURPOSE: S100A9 protein induces anti-nociception in rodents, in
      different experimental models of inflammatory pain. Herein, we investigated the
      effects of a fragment of the C-terminus of S100A9 (mS100A9p), on the hyperalgesia
      induced by serine proteases, through the activation of protease-activated
      receptor-2 (PAR2). EXPERIMENTAL APPROACH: Mechanical and thermal hyperalgesia
      induced by PAR2 agonists (SLIGRL-NH2 and trypsin) was measured in rats submitted
      to the paw pressure or plantar tests, and Egr-1 expression was determined by
      immunohistochemistry in rat spinal cord dorsal horn. Calcium flux in human
      embryonic kidney cells (HEK), which naturally express PAR2, in Kirsten virus
      transformed kidney cells, transfected (KNRK-PAR2) or not (KNRK) with PAR2, and in
      mouse dorsal root ganglia neurons (DRG) was measured by fluorimetric methods. KEY
      RESULTS: mS100A9p inhibited mechanical hyperalgesia induced by trypsin, without
      modifying its enzymatic activity. Mechanical and thermal hyperalgesia induced by
      SLIGRL-NH2 were inhibited by mS100A9p. SLIGRL-NH2 enhanced Egr-1 expression, a
      marker of nociceptor activation, and this effect was inhibited by concomitant
      treatment with mS100A9p. mS100A9p inhibited calcium mobilization in DRG neurons
      in response to the PAR2 agonists trypsin and SLIGRL-NH2, but also in response to
      capsaicin and bradykinin, suggesting a direct effect of mS100A9 on sensory
      neurons. No effect on the calcium flux induced by trypsin or SLIGRL in HEK cells
      or KNRK-PAR2 cells was observed. CONCLUSIONS AND IMPLICATIONS: These data
      demonstrate that mS100A9p interferes with mechanisms involved in nociception and
      hyperalgesia and modulates, possibly directly on sensory neurons, the PAR2
      induced nociceptive signal.

PMID- 16967050
TI  - Sustained contraction and loss of NO production in TGFbeta1-treated endothelial
      cells.
AB  - BACKGROUND AND PURPOSE: Transforming growth factor beta1 (TGFbeta1) is generated
      in atherosclerotic and injured vessel walls. We examined whether the endothelial
      to-mesenchymal transdifferentiation induced by TGFbeta1 affects endothelial
      functions. EXPERIMENTAL APPROACH: Bovine aortic endothelial cells (BAECs) were
      treated with 3 ng ml(-1) TGFbeta1 for 7 days. Contraction of TGFbeta1-treated
      BAECs was assessed by collagen gel contraction assay. Protein expression and
      phosphorylation were assessed by Western blotting. Intracellular Ca2+
      concentration and NO production were measured using fura2 and DAF-2,
      respectively. KEY RESULTS: TGFbeta1-treated BAECs showed dense actin fibers and
      expressed smooth muscle marker proteins; they also changed into smooth muscle
      like, spindle-shaped cells in collagen gel cultures. ATP (10 microM) induced a
      gradual contraction of collagen gels containing TGFbeta1-treated BAECs but not of
      gels containing control BAECs. ATP-induced contraction of TGFbeta1-treated BAECs
      was not reversed by the removal of ATP but was partially suppressed by a high
      concentration of sodium nitroprusside (1 microM). TGFbeta1-treated BAECs showed
      sustained phosphorylation of myosin light chain in response to ATP and low levels
      of basal MYPT1 expression. ATP-induced Ca2+ transients as well as eNOS protein
      expression were not affected by TGFbeta1 in BAECs. However, ATP-induced NO
      production was significantly reduced in TGFbeta1-treated BAECs. Anti-TGFbeta1
      antibody abolished all of these TGFbeta1-induced changes in BAECs. CONCLUSIONS
      AND IMPLICATIONS: Mesenchymal transdifferentiation induced by TGFbeta1 leads to
      sustained contraction and reduced NO production in endothelial cells. Such
      effects, therefore, would not be beneficial for vascular integrity.

PMID- 16967052
TI  - Effects of pyrrophenone, an inhibitor of group IVA phospholipase A2, on
      eicosanoid and PAF biosynthesis in human neutrophils.
AB  - BACKGROUND AND PURPOSE: The biosynthesis of leukotrienes (LT) and platelet
      activating factor (PAF) involves the release of their respective precursors,
      arachidonic acid (AA) and lyso-PAF by the group IVA PLA2 (cPLA2alpha). This paper
      aims at characterizing the inhibitory properties of the cPLA2alpha inhibitor
      pyrrophenone on eicosanoids and PAF in human neutrophils (PMN). EXPERIMENTAL
      APPROACH: Freshly isolated human PMN were activated with physiological and
      pharmacological agents (fMLP, PAF, exogenous AA, A23187 and thapsigargin) in
      presence and absence of the cPLA2alpha inhibitor pyrrophenone and biosynthesis of
      LT, PAF, and PGE2 was measured. KEY RESULTS: Pyrrophenone potently inhibited LT,
      PGE2 and PAF biosynthesis in PMN with IC50s in the range of 1-20 nM. These
      inhibitory effects of pyrrophenone were specific (the consequence of substrate
      deprivation), as shown by the reversal of inhibition by exogenous AA and lyso
      PAF. Comparative assessment of pyrrophenone, methyl-arachidonoyl-fluoro
      phosphonate (MAFP) and arachidonoyl-trifluoromethylketone (AACOCF3) demonstrated
      that pyrrophenone was more specific and 100-fold more potent than MAFP and
      AACOCF3 for the inhibition of LT biosynthesis in A23187-activated PMN. The
      inhibitory effect of pyrrophenone on LT biosynthesis was reversible as LT
      biosynthesis was recovered when pyrrophenone-treated PMN were washed with
      autologous plasma. No alteration of phospholipase D (PLD) activity in fMLP
      activated PMN was observed with up to 10 microM pyrrophenone, suggesting that the
      cPLA2alpha inhibitor does not directly inhibit PLD. CONCLUSIONS AND IMPLICATIONS:
      Pyrrophenone is a more potent and specific cPLA2alpha inhibitor than MAFP and
      AACOCF3 and represents an excellent pharmacological tool to investigate the
      biosynthesis and the biological roles of eicosanoids and PAF.

PMID- 16967051
TI  - Collagen impairs glucocorticoid actions in airway smooth muscle through integrin
      signalling.
AB  - BACKGROUND AND PURPOSE: Airway wall remodelling in asthma is characterised by a
      number of structural changes, including an increase in the volume of airway
      smooth muscle (ASM), and the abundance of the extracellular matrix (ECM) protein,
      collagen, is increased. We have investigated the mechanism of collagen-induced
      glucocorticoid resistance of proliferation, and migration of ASM. EXPERIMENTAL
      APPROACH: ASM cultured from human airways has been seeded on to either type I
      monomeric collagen or a laminin pentapeptide, YIGSR. The role of alpha2beta1
      integrin in the collagen-induced glucocorticoid resistance was investigated using
      a function blocking monoclonal antibody. KEY RESULTS: Culture of ASM on collagen
      I, but not laminin, led to a greater proliferative response that was insensitive
      to regulation by dexamethasone (100 nM). The anti-migratory effects of the
      glucocorticoid, fluticasone propionate (1 nM) were also impaired by contact of
      ASM with collagen. The impaired anti-mitogenic action of dexamethasone was
      associated with a failure to reduce the levels of the rate-limiting cell cycle
      regulatory protein, cyclin D1. When signalling through the alpha2beta1 integrin
      was reduced, dexamethasone-mediated reductions in proliferation and cyclin D1
      levels were restored. CONCLUSIONS AND IMPLICATIONS: In the collagen-rich
      microenvironment of the inflamed and fibrotic asthmatic airway, integrin/ECM
      interactions may contribute to glucocorticoid resistance.

PMID- 16967053
TI  - Cellular effects and metabolic stability of N1-cyclic inosine diphosphoribose and
      its derivatives.
AB  - BACKGROUND AND PURPOSE: Recently, a number of mimics of the second messenger
      cyclic ADP-ribose (cADPR) with replacement of adenosine by inosine were
      introduced. In addition, various alterations in the molecule ranging from
      substitutions at C8 of the base up to full replacement of the ribose moieties
      still retained biological activity. However, nothing is known about the metabolic
      stability and cellular effects of these novel analogues. EXPERIMENTAL APPROACH:
      cADPR and the inosine-based analogues were incubated with CD38, ADP-ribosyl
      cyclase and NAD-glycohydrolase and metabolism was analysed by RP-HPLC.
      Furthermore, the effect of the analogues on cytokine expression and proliferation
      was investigated in primary T-lymphocytes and T-lymphoma cells. KEY RESULTS:
      Incubation of cADPR with CD38 resulted in degradation to adenosine
      diphosphoribose. ADP-ribosyl cyclase weakly catabolised cADPR whereas NAD
      glycohydrolase showed no such activity. In contrast, N1-cyclic inosine 5'
      diphosphoribose (N1-cIDPR) was not hydrolyzed by CD38. Three additional N1-cIDPR
      analogues showed a similar stability. Proliferation of Jurkat T-lymphoma cells
      was inhibited by N1-cIDPR, N1-[(phosphoryl-O-ethoxy)-methyl]-N9-[(phosphoryl-O
      ethoxy)-methyl]-hypoxanthine-cyclic pyrophosphate (N1-cIDP-DE) and N1
      ethoxymethyl-cIDPR (N1-cIDPRE). In contrast, in primary T cells neither
      proliferation nor cytokine expression was affected by these compounds.
      CONCLUSIONS AND IMPLICATIONS: The metabolic stability of N1-cIDPR and its
      analogues provides an advantage for the development of novel pharmaceutical
      compounds interfering with cADPR mediated Ca2+ signalling pathways. The
      differential effects of N1-cIDPR and N1-cIDPRE on proliferation and cytokine
      expression in primary T cells versus T-lymphoma cells may constitute a starting
      point for novel anti-tumor drugs.

PMID- 16967054
TI  - Meeting the support and information needs of women with advanced breast cancer: a
      randomised controlled trial.
AB  - Addressing psychosocial and quality of life needs is central to provision of
      excellent care for people with advanced cancer. This study tested a brief nurse
      delivered intervention to address the needs of urban women with advanced breast
      cancer. This study was conducted at four large urban hospitals in Australia. One
      hundred and five women with advanced breast cancer were recruited and randomised
      to receive the intervention or usual care, then asked to complete the European
      Organisation of Research and Treatment of Quality of life Q-C30 version (2.0)
      (EORTC Q-C30) (version 2) and Supportive Care Needs Survey (SCNS) at 1 month and
      3 months postrecruitment. No significant differences were detected between
      intervention and usual care groups in the SCNS or the EORTC Q-C30 subscale
      scores. However, when the groups were divided into high needs (score of above 50)
      and low baseline needs (score of 50 or below) for each SCNS subscale, a
      significant difference between intervention and usual care groups was found in
      the psychological/emotional subscale among women with high baseline needs. In
      conclusions, this study demonstrated that a face-to-face session and follow-up
      phone call with a breast care nurse significantly reduced the psychological and
      emotional needs of those with high initial needs. There was no evidence of the
      intervention influencing the quality of life; or perceived needs of women with
      low initial psychological/emotional needs or perceived needs in other domains.
      Possibly, the intervention was not sufficiently intense to achieve an effect.

PMID- 16967055
TI  - Health state utilities for metastatic breast cancer.
AB  - The aim of the study was to obtain United Kingdom-based societal preferences for
      distinct stages of metastatic breast cancer (MBC) and six common toxicities.
      Health states were developed based on literature review, iterative cycles of
      interviews and a focus group with clinical experts. They described the burden of
      progressive, responding and stable disease on treatment; and also febrile
      neutropenia, stomatitis; diarrhoea/vomiting; fatigue; hand-foot syndrome (grade
      3/4 toxicities) and hair loss. One hundred members of the general public rated
      them using standard gamble to determine health state utility. Data were analysed
      with a mixed model analysis. The study sample was a good match to the general
      public of England and Wales by demographics and current quality of life. Stable
      disease on treatment had a utility value of 0.72, with a corresponding gain of
      +0.07 following a treatment response and a decline by 0.27 for disease
      progression. Toxicities lead to declines in utility between 0.10
      (diarrhoea/vomiting) and 0.15 (febrile neutropenia). This study underlines the
      value that society place on the avoidance of disease progression and severe side
      effects in MBC. This may be the largest preference study in breast cancer
      designed to survey a representative general public sample.

PMID- 16967058
TI  - [New, true and interesting].

PMID- 16967056
TI  - Induction cisplatin-irinotecan followed by concurrent cisplatin-irinotecan and
      radiotherapy without surgery in oesophageal cancer: multicenter phase II FFCD
      trial.
AB  - A recent phase I study showed that weekly cisplatin, irinotecan and concurrent
      radiotherapy can be administered with moderate toxicity in patients with
      oesophageal cancer. Patients with no prior treatment and oesophageal cancer stage
      I to III, performance status <3, caloric intake >1,500 kcal day(-1) were
      included. Chemotherapy, with cisplatin 30 mg m(-2) and irinotecan 60 mg m(-2),
      was administered at days 1, 8, 22, 29, and concurrently with radiotherapy at days
      43, 50, 64 and 71. Radiotherapy was delivered with 50 or 50.4 Gy in 25
      fractions/5 weeks. Forty-three patients were included, 10 stage I, 19 stage II
      and 14 stage III. Mean age was 59.2 years (range 44-79). A total of 30 out of 43
      (69.8%) patients underwent all planned treatment. During induction chemotherapy,
      14 severe toxicities of grade 3 or 4 in 10 patients (23.3%) were reported with
      57.1% due to haematoxicity. During chemoradiotherapy, 31 severe toxicities of
      grade 3 or 4 with 64.5% due to haematotoxicity were reported in 18 patients. One
      toxic death occurred (diarrhoea grade 4). The complete clinical response rate was
      58.1% (95% CI: 43.4-72.8%). Overall survival rate at 1 and 2 years was 62.8%,
      (95% CI, 58.3-77.3%) and 27.9% (95% CI, 13.4-41.3%), respectively. In conclusion,
      cisplatin-irinotecan-radiotherapy is an active and well-tolerated regimen
      feasible in out-patients.

PMID- 16967059
TI  - [How to prevent amputation in diabetes].

PMID- 16967060
TI  - [Changes in cardiovascular risk factors among men in Oslo during 28 years].
AB  - BACKGROUND: The aim of the study was to measure changes in known risk factors for
      cardiovascular disease among men over a period of 28 years. MATERIAL AND METHODS:
      The present cohort study comprises a selection of men previously included in the
      Oslo-study of 1972/73. The men selected, were either followed-up in the Oslo II
      study (n = 5,323), or were included in five other studies in the period 1996-2001
      (n = 1,834). The total material is named The second screening of the Oslo-study
      and consists of 7157 men. RESULTS: The men were born between 1923 and 1952. All
      age groups showed a marked increase in mean weight by 4.4 Kg. Body Mass Index
      changed from 24.3 to 26.4 kg/m2 , coinciding with reduced level of physical
      activity in all age groups. A comparison of body mass index in men of the same
      age in 1972/73 and 2000, show a mean increase in body mass index of two units. An
      increase of 0.30 mmol/L glucose (non-fasting) was observed. Total cholesterol
      decreased from 6.19 to 5.95 mmol/L and triglycerides remained unchanged (1.89 to
      1.87 mmol/L). Systolic blood pressure increased but not the diastolic pressure.
      Overall 30.8 % of the men took medication for increased blood pressure, versus
      3.1 % at the first screening. The percentage of daily smokers decreased from 44.2
      % to 17.4 %. INTERPRETATION: The most encouraging result was the strong reduction
      in number of daily smokers. The study confirms the weight increase observed among
      men in Norway.

PMID- 16967061
TI  - [Is a healthy lifestyle worthwhile?].
AB  - BACKGROUND: The men invited to participate in the Oslo Study in 1972/3 were
      invited again to participate in the Oslo II study in 2000. We examined whether
      self-reported lifestyle habits were associated with biological markers, a range
      of symptoms and several illnesses in 2000. MATERIAL AND METHODS: In addition to
      data from Oslo II, were data from those men of the Oslo-cohort who participated
      in 5 other studies between 1998 and 2001. The total material is named The second
      screening of the Oslo-study. Levels of lipids and glucose, height, weight, waist
      and hip circumferences and blood pressure were measured in 6,410 men born in 1923
      32 that participated in both surveys. Participants were divided into four groups
      according to their lifestyle habits in both surveys, as follows: unhealthy,
      somewhat unhealthy, somewhat healthy and healthy lifestyle. RESULTS: Participants
      with a healthy lifestyle had a lower number of symptoms and illnesses, prevalence
      of the metabolic syndrome and waist-hip ratio, compared to those with a less
      healthy lifestyle. The number of men with psychological distress leading to
      treatment, was inversely associated with an increasingly healthy lifestyle. After
      adjustment for level of education and smoking in both 1972/3 and in 2000, the
      relationship between health profile and lifestyle became more linear.
      INTERPRETATION: A healthy lifestyle was associated with protective levels of risk
      factors and lower prevalences of a wide range of illnesses.

PMID- 16967062
TI  - [Syncope in children and young adults].
AB  - BACKGROUND: 15-40% of children and young adults have had at least one episode of
      syncope. The most frequent types are the reflex-mediated syncopes (60-70%). 5-6 %
      are cardiac syncopes that include several life-threatening diseases that are
      essential to diagnose. This article presents reasons, assessment and treatment of
      syncopes in children and young adults. MATERIAL: PubMed has been searched for
      relevant literature. RESULTS: A thorough medical history, ECG and
      echocardiography can reveal life-threatening cardiac causes of syncope. Reflex 
      mediated syncopes often have a typical history and always completely normal
      physical examinations and ECGs. A tilt test can be necessary and give further
      information. Cardiac syncope often occurs suddenly or during exercise. Reflex
      syncopes are treated with education, medication and sometimes insertion of a
      pacemaker. Treatment of cardiac syncope depends on the underlying disease and
      includes medication and device therapy. CONCLUSION: Syncopes in children and
      young adults are mostly benign, but diagnosis of underlying life- threatening and
      treatable cardiac disease is essential.

PMID- 16967063
TI  - [Corticosteroids in the treatment of HELLP-syndrome?].
AB  - BACKGROUND: Haemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome
      is a severe form of preeclampsia. It is often manifested clinically by elevated
      blood pressure, proteinuria and abdominal pain. Women diagnosed with the HELLP
      syndrome normally show evidence of recovery within the first 48 hours after
      delivery. There is however a small group of patients in which no arrest or
      reversal of the HELLP process can be seen after 72 hours post partum. These
      patients have a high incidence of maternal morbidity and mortality. Several
      studies have shown benefits to HELLP patients after administration of
      corticosteroids. MATERIAL AND METHODS: We have reviewed the literature for this
      treatment and present a case report as illustration. PubMed/Medline was searched
      with the key words "HELLP and corticosteroids" from 1990 to 2006. We have chosen
      to review the prospective and randomised studies. RESULTS AND INTERPRETATION:
      None of the studies show statistically significant differences in maternal
      morbidity or mortality by administering corticosteroids to patients with HELLP
      syndrome. Treatment can give a faster increase in the platelet count for patients
      with platelets < 50 (10(9)/L), but larger trials are needed to support the use of
      corticosteroids for treatment of HELLP-syndrome.

PMID- 16967064
TI  - [On-site testing for drug abuse in urine].
AB  - BACKGROUND: There is an increasing interest in on-site testing for drugs of
      abuse. METHODS: Based upon our own experience and published literature, we have
      reviewed advantages and disadvantages of such tests. On-site testing is also
      evaluated in relation to the recommendations for urinary testing of drugs of
      abuse from the Norwegian Health Authorities. RESULTS: The most significant
      advantage with on-site testing is provision of rapid results, usually within 5-10
      minutes. Disadvantages are the risks of false positive and false negative
      results, the fact that numerous drugs cannot be tested for, and the limited
      possibilities to detect manipulation. According to Norwegian regulations, on-site
      testing can be used for medical purposes, but cannot be used as the only method
      if a positive result may cause sanctions such as e.g. exclusion from school, job
      dismissal or loss of parental rights. There are also special requirements for the
      organization of such testing. INTERPRETATION: Before starting on-site testing for
      drugs of abuse, it should be considered if such testing is allowed or discouraged
      in the specific case. It is mandatory to know how the specific test works and to
      have routines for follow-up of positive test results.

PMID- 16967065
TI  - [Lower-limb amputations and diabetes].
AB  - BACKGROUND: A reduced incidence of lower-limb amputations in diabetic patients is
      a highly prioritised goal. The frequency and prognosis of amputations in our
      hospital area was recorded in the present study. MATERIAL AND METHODS: All
      patient records from 1990 to 1999 from the hospitals in Hamar and Elverum, with
      operation codes for lower-limb amputations, were examined. Known diabetes,
      smoking status, previous angiography or vascular surgery, and survival until
      January 31st 2002 were recorded. RESULTS: 412 amputations in 270 patients were
      recorded. 118 patients (44%) had diabetes, 96% of them had diabetes type 2.
      Diabetic patients were subject to 51% of the amputations. On average, 0.31% of
      known diabetic patients in our hospital area had amputations of lower-limb(s)
      annually during the study period. The mean annual incidence of amputations in
      diabetic persons was 550 per 100,000 and in non-diabetics 17 per 100,000. The
      mean age at the first amputation was 77 years. Multiple and distal operations
      were more frequent in diabetics. Mortality 30 days after the first amputation was
      11% in diabetics and 24% in non-diabetics and after one year it was 32% for
      diabetics and 51% for non-diabetics. INTERPRETATION: The amputation frequency in
      our hospital area is similar to that in other parts of Norway. About one half of
      lower-limb amputations are performed in diabetic patients. Most amputees are old
      and mortality after amputation is high.

PMID- 16967066
TI  - [Impaired glucose tolerance in patients with acute myocardial infarction].
AB  - BACKGROUND: Diabetes and impaired glucose tolerance are associated with increased
      mortality in patients with acute myocardial infarction. We have used standardised
      oral glucose tolerance tests shortly after a myocardial infarction. METHODS: 109
      patients admitted with acute myocardial infarction were prospectively enrolled in
      the study. An oral glucose tolerance test was performed the first morning the
      patients were stable, without pain, nausea or hyperglycaemia. The patients were
      classified into normal glucose tolerance, impaired glucose tolerance or diabetes,
      according to the results of the oral glucose tolerance test and fasting plasma
      glucose levels. RESULTS: 109 patients (25 women) were included. Eight patients
      were previously diagnosed with diabetes type 2. Oral glucose tolerance was tested
      for 90 patients, usually the day after admission. The test was positive in 47
      patients; 32 of them had 2-h plasma glucose levels between 7.8 and 11.0 mmol/L
      and were classified as having impaired glucose tolerance, and 15 had 2-h plasma
      glucose > or = 11.1 mmol/L and were classified as newly diagnosed diabetes
      patients. Similar body mass indexes and lipid values were found in patients with
      different glycometabolic states. Smoking was associated with a positive oral
      glucose tolerance test. INTERPRETATION: More than half of the patients with acute
      myocardial infarction had undiagnosed impaired glucose tolerance or diabetes type
      2, as determined by an oral glucose tolerance test. The test could easily be
      performed shortly after a myocardial infarction in most of the patients. Oral
      glucose tolerance testing should be considered in all patients with coronary
      heart disease without a history of diagnosed diabetes.

PMID- 16967067
TI  - [False measurement of glucose during dialysis with icodextrin].
AB  - BACKGROUND: Recent reports have indicated that icodextrin may interfere with
      glucose assays when patients are treated with icodextrin for peritoneal dialysis
      (PD). We wished to examine whether icodextrin interfered with plasma glucose, as
      measured with new instruments commonly used for glucose measurements in Norway.
      MATERIAL AND METHODS: Serum and plasma glucose were measured in a diabetic
      patient (type II) who had started PD with icodextrin. Serum glucose was measured
      simultaneously in venous blood using the laboratory reference method
      (hexokinase), and compared with eight point of care testing (POCT) glucometers.
      The instruments used glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ),
      glucose dehydrogenase nicotinamide adenine dinucleotide (GDH- NAD), or glucose
      oxidase (GOx) methods. RESULTS: The laboratory reference method for glucose
      measurements was not affected by icodextrin. Biosensors with GDH-NAD and GOx
      methods did not give falsely elevated glucose results. Two of the eight POCT
      glucometers used the GDH-PQQ method. Both Ascensia Contour (Bayer HealthCare) and
      Accu-Chek (Roche Diagnostics) showed more than 60 % higher glucose values than
      the reference method. INTERPRETATION: The GDH-PQQ method is non-specific for
      measurements of glucose. Over-estimation of glucose may result in unrecognized
      hypoglycaemia. POCT glucometers with a GDH-PQQ based monitoring system should not
      be used in diabetics receiving icodextrin for PD. The patients and caregivers
      must be informed about which glucometers to use.

PMID- 16967068
TI  - [Opioid switching and methadone in pain relief].

PMID- 16967069
TI  - [Increased risk of testicular dysgenesis?].
AB  - The latest figures from the Cancer Registry of Norway show that Norway has the
      highest incidence rate of testicular cancer in the world. They also show that the
      incidence rate continues to increase, as it has for the last decades in the
      western world. The reasons for this increase, which might also be true for
      urogenital abnormalities in men and reduced sperm quality, are uncertain. Data
      suggest, however, that these anomalies originate in foetal life, and that
      contributing factors are genetic, pregnancy-related and environmental. The
      potential importance of environmental factors must be taken seriously, and the
      authorities must take action to strengthen the research in this area.

PMID- 16967070
TI  - [Co-sleeping and baby-controlled breast feeding].

PMID- 16967071
TI  - [This is not our medical ethic].

PMID- 16967073
TI  - [Abortion--more than numbers, more than the Tidsskrift].

PMID- 16967074
TI  - [Will Tidsskriftet go on censoring openness about abortions?].

PMID- 16967076
TI  - [Epicrisis to the admitting physician].

PMID- 16967077
TI  - [Gluten intolerance, hypothyroidism, lactose and fructose malabsorption--a new
      "syndrome"?].

PMID- 16967078
TI  - [A wonder about Tidskriftet's prioritization].

PMID- 16967079
TI  - [Retraction of: Diagnostics and treatment of early stages of oral cancer].
AB  - The undersigned, who are co-authors of the article Diagnostics and treatment of
      early stages of oral cancer, wish to retract it. The reason is that the basis for
      the review article has been shown to be false. A review committee, that has
      assessed the research activity of the main author, has concluded that the data in
      this article are fabricated. We can no longer stand behind the article and hereby
      retract it.

PMID- 16967080
TI  - [Retraction of: Chemoprevention of oral cancer].
AB  - On the basis of the Review Committee's conclusions on Jon Sudbo's research, the
      Journal of the Norwegian Medical Association has decided to retract the article
      Chemoprevention of oral cancer.

PMID- 16967082
TI  - [The occupational environment legislation and physicians' working situation].

PMID- 16967084
TI  - [Antiretroviral therapy in Poipet].

PMID- 16967086
TI  - Application of biochemical markers for identification of biological properties of
      animal semen.
AB  - The use of biochemical markers for identification of biological properties of
      semen will help to develop new criteria that are accurate and objective in
      predicting and improving male fertility. Understanding and controlling the
      mechanisms involved in fertility is a key challenge, which is of fundamental
      importance in successful animal reproductive performance. Moreover, unraveling
      the unique molecular mechanism associated with sperm function might have
      considerable diagnostic value in the evaluation of male infertility. This review
      offered insights into some recent achievements and provided perspectives for
      possible applications of the biochemical markers of semen.

PMID- 16967087
TI  - Genetical and biotechnological methods of utilization of female reproductive
      potential in mammals.
AB  - The investigations included: 1/ Establishment of culture systems that would
      maintain the three-dimensional structure of bovine intact early antral follicles
      (EAF) or isolated cumulus-oocyte-granulosa complexes (COCGs) and increase the
      resulting portion of cumulus-oocyte complexes (COCs) with normal morphology for
      subsequent in vitro maturation (IVM) and in vitro fertilization (IVF), 2/ Quality
      assessment of IVM bovine oocytes and resulting day-8 blastocysts produced in
      TCM199 medium supplemented with fetal bovine serum (FBS), fatty acid free bovine
      serum albumin (fafBSA) or polyvinylpyrrolidone (PVP40), 3/ Testing the
      polymorphism of the genes: retinol binding protein (RBP4), epidermal growth
      factor (EGF), prostaglandin-endoperoxide synthase 2 (PTGS2), insulin-like growth
      factor 2 (IGF2), amphiregulin (AREG) and prolactin (PRL), and their effects on
      reproductive traits in swine. Isolated COCGs created in culture follicle-like
      structures and their oocytes achieved meiotic competence and matured to metaphase
      II at a higher rate than did oocytes from smaller diameter follicles which were
      cultured intact. The proportion of COCs with normal morphology significantly
      increased when isolated COCGs were embedded in microdrops of collagen gel or
      cultured on inserts covered with gel rather than in large gel volumes. No
      significant effect of maturation media composition on meiotic spindle morphology
      and the rate of apoptotic bovine oocytes was observed. Among day-8 embryos
      derived from oocytes matured with PVP40 a reduced blastocyst rate and elevated
      apoptotic index were found, whereas total cell count was not affected. Gene
      expression study also revealed a decrease in relative abundance for IGF2 and its
      receptor (IGF2R), and heat shock protein 70 (Hsp70) genes in PVP40 group and a
      significant elevation in fafBSA derived embryos. The significant effect of
      reproduction traits of swine (litter size and litter weight) was found for RBP4,
      EGF, IGF2 and AREG genes. A new polymorphism was also revealed within a promoter
      region of PRL gene.

PMID- 16967088
TI  - Candidate mRNAs interacting with fertility protein PUMILIO2 in the human germ
      line.
AB  - Pumilio protein regulates translation of specific mRNAs in morphogenesis and germ
      line development of the flies by binding nucleotide motifs GUUGU (A) and AUUGUA
      (B) in 3'untranslated regions. A human homologue, PUMILIO2 has been recently
      identified in the germ-line stem cells and the question was raised whether it
      regulates translation. We designed software to screen the GeneBank for A and B
      motifs and found that they are not uncommon in the human genome. Moreover, some
      of the genes containing motifs A and B are germ cell specific, but some others
      are expressed in a number of other tissues. This may indicate that PUMILIO
      mediated translational regulation is universally used in developmental processes
      of the human body.

PMID- 16967089
TI  - Hormonal status of male reproductive system: androgens and estrogens in the
      testis and epididymis. In vivo and in vitro approaches.
AB  - The purpose of this article was to summarize our results on the role of androgens
      and estrogens in human, rodent and equine testes and epididymides, in both,
      physiological and patological conditions, obtained in the space of the Solicited
      Project (084/PO6/2002) financially supported by the State Committee for
      Scientific Research during the last three years. Testosterone produced by Leydig
      cells of the testes is clearly the major androgen in the circulation of men and
      adult males of most mammalian species. However, androgen metabolites make up a
      significant fraction of total circulating steroids. Moreover, androgen metabolism
      may proceed to amplify the action of testosterone through its conversion to
      dihydrotestosterone (DHT) or its aromatization to estradiol. The distribution of
      androgen and estrogen receptors (ARs and ERs) within male reproductive tissues is
      important because of their crucial role in mediating androgen and/or estrogen
      action. Attempts were undertaken to discuss not only the role of aromatase and
      ERs in mediating the action of estrogens in the male, but also the importance of
      DHT in hormonal regulation of the epididymis. In the latter, alterations caused
      by finasteride treatment and lead-induced oxidative stress are described. Male
      reproductive function of the testis and epididymis reflected by the alterations
      in enzymatic activity, distribution of steroid hormone receptors, differences in
      steroid hormone levels and altered gene expression of antioxidant enzymes are
      also discussed.

PMID- 16967090
TI  - Mechanisms ensuring optimal conditions of implantation and embryo development in
      the pig.
AB  - The paper summarizes results of a series of studies concerning luteolysis and
      early pregnancy in pigs. The involvement of the oxytocin (OT)/OT receptor system
      in the mechanism of corpus luteum (CL) protection during early pregnancy as well
      as the implication of luteinizing hormone (LH) in the endometrial prostaglandin
      (PG) release and synthesis are described. In addition, the role of leptin in the
      regulation of ovarian steroidogenesis and the expression of leptin and its
      receptor (OB-Rb) genes in hypothalamus, pituitary and reproductive tissues are
      reported. Moreover, a strong emphasis was placed on the mechanism of PGE2
      participation in the local endocrine regulations of reproductive processes
      occurring in the utero-ovarian area as well as on the vascular endothelial growth
      factor (VEGF) ligand-receptor system in the ovary and uterus.

PMID- 16967091
TI  - Aspects of central and peripheral regulation of reproduction in mammals.
AB  - To increase our knowledge concerning the central and peripheral regulation of
      reproduction in mammals a series of studies were performed. In the first
      experiment, we found that exogenous leptin altered the activity of the hypothalmo
      pituitary-gonadotropic axis in sheep during insufficient feeding. The action of
      leptin appears to be mediated by changes in GnRH and LH secretion as well as NPY
      immunoreactivity. The aim of the second experiment was to investigate the role of
      the adipoinsular axis hormones during pregnancy in rats. The elevated levels of
      plasma leptin as wells as the increased mRNAs expression of the leptin receptors
      in placenta indicate the significant role of the hormone in fetal growth and
      development. On the other hand, a decrease in leptin receptors mRNA content
      within hypothalamus and pituitary together with unchanged plasma insulin level
      may suggest that during rat pregnancy leptin resistance was developed in the
      hypothalamus, pituitary and pancreatic islets. The third experiment was carried
      out to establish the role of opioids and glucocorticoids in the regulation of the
      hypothalmo-pituitary-gonadal axis in ewes during natural or synchronized estrous
      cycle. Prolonged treatment with progesterone resulted in significant changes in
      plasma levels of Met-enkephalin, cortisol and steroids and altered the expression
      of proenkephalin mRNA in the hypothalamus, pituitary, ovary and adrenals.
      Injections of Met-enkephalin or naltrexone (blocker of opioid receptors)
      modulated the progesterone influence in tested tissues. The data clearly suggest
      that opioids are involved in the regulation of the estrous cycle at the
      hypothalamo-pituitary-gonadal/adrenal axes.

PMID- 16967092
TI  - Porcine pregnancy-associated glycoprotein family (pPAGs) - as in vitro-produced
      chorionic ligands for luteal and uterine gonadotropin receptors.
AB  - This paper compares proteomic interaction-types and binding-effectiveness of
      secretory chorionic ligands (including pPAGs) with other proteins, i.e.
      gonadotropin membrane receptors (Rc) isolated from luteal-phase corpora lutea,
      uterine myometrium and endometrium of cyclic (cCLRc, cMYORc and cENDRc) or
      pregnant (pCLRc, pMYORc and pENDRc) pigs. Binding-effectiveness of miscellaneous
      in vitro-produced chorionic ligands (+pPAGs) was compared by radioreceptor assay
      (RRA) with endometrial (END) proteins of cyclic, pseudopregnant and pregnant
      gilts - as negative control ligands and porcine LH and hCG - as positive control
      ligands. The binding-comparison suggests that the pPAGs may play an important
      role as potential antiluteolytic or luteoprotective chorionic-origin signals
      during pregnancy, according to the binding-effectiveness of secretory chorionic
      ligands (+pPAGs) that was relatively comparable to LH/hCG - as classical ligands
      competing for luteal and uterine gonadotropin receptors of cyclic and pregnant
      pigs.

PMID- 16967093
TI  - Androgen receptor in the reproductive systems of pregnant pigs and rats.
AB  - The immunohistochemical expression of the androgen receptor (AR) was investigated
      in the ovarian atretic follicles and corpora lutea (CL) of pregnant pigs and
      rats, as well as in porcine uteri and fetuses. Follicular atresia involved either
      abnormal persistence or depletion of AR in various follicular compartments.
      Porcine and rat CL expressed nuclear AR. However, in the porcine CL, starting
      from day 70 of pregnancy, mainly cytoplasmic staining was observed, with
      exclusively cytoplasmic expression found on day 90. In the CL of pregnant rats,
      differences in AR distribution within the same CL were observed and decreasing AR
      expression during luteal regression was found. AR mRNA and protein expression in
      the porcine uterus depended on the uterine compartment and the day of pregnancy.
      AR-positive were also testes, ovaries, uteri, kidneys and lungs of fetuses.

PMID- 16967094
TI  - Generation of cloned and chimeric embryos/offspring using the new methods of
      animal biotechnology.
AB  - The article summarizes results of studies concerning: 1/ qualitative evaluation
      of pig nuclear donor cells to somatic cell cloning, 2/ developmental potency of
      sheep somatic cells to create chimera, 3/ efficient production of chicken
      chimera. The quality of nuclear donor cells is one of the most important factors
      to determine the efficiency of somatic cell cloning. Morphological criteria
      commonly used for qualitative evaluation of somatic cells may be insufficient for
      practical application in the cloning. Therefore, different types of somatic cells
      being the source of genomic DNA in the cloning procedure were analyzed on
      apoptosis with the use of live-DNA or plasma membrane fluorescent markers. It has
      been found that morphological criteria are a sufficient selection factor for
      qualitative evaluation of nuclear donor cells to somatic cell cloning.
      Developmental potencies of sheep somatic cells in embryos and chimeric animals
      were studied using blastocyst complementation test. Fetal fibroblasts stained
      with vital fluorescent dye and microsurgically placed in morulae or blastocysts
      were later identified in embryos cultured in vitro. Transfer of Polish merino
      blastocysts harbouring Heatherhead fibroblasts to recipient ewes brought about
      normal births at term. Newly-born animals were of merino appearance with dark
      patches on their noses, near the mouth and on their clovens. This overt chimerism
      shows that fetal fibroblasts introduced to sheep morulae/blastocysts revealed
      full developmental plasticity. To achieve the efficient production of chicken
      chimeras, the blastodermal cells from embryos of the donor breeds, (Green-legged
      Partridgelike breed or GPxAraucana) were transferred into the embryos of the
      recipient breed (White Leghorn), and the effect of chimerism on the selected
      reproductive and physiological traits of recipients was examined. Using the model
      which allowed identification of the chimerism at many loci, it has been found
      that 93.9% of the examined birds were chimeras. The effect of donor cells on the
      reproduction and physiology of the recipients was evident.

PMID- 16967095
TI  - Season controlled reproduction of undomesticated animals.
AB  - The following article is a summary of research on the influence of season on the
      reproductive processes in undomesticated animals. The results presented below
      show: a/ an annual hormonal profile of domestic pig and wild boar crossbreed and
      the antioxidant blood system in the different seasons, b/ the possibility of
      gonadptropic hormone stimulation in chinchillas which are in diestrus or
      infertile, c/ the possibility of using bison's semen (collected post mortem from
      the epididymis) for cryoconservation.

PMID- 16967096
TI  - Mechanism of phytoestrogens action in reproductive processes of mammals and
      birds.
AB  - Phytoestrogens are polyphenolic compounds that occur ubiquitously in food of
      plant origin and they have a variety of biological effects in numerous animal
      cell systems in vivo as well in vitro. Results of studies conducted on animals
      have shown that effects of phytoestrogens vary depending on species, sex, routes
      of administration, dose and exposure time. This review summarizes the results of
      ours studies concerning: 1/ molecular mechanism of phytoestrogen action in
      porcine granulosa cells, 2/ the involvement of phytoestrogens in immunological
      regulations of bovine corpus luteum function during luteolysis, 3/ genistein
      action on metabotropic hormones and lipid-carbohydrate metabolism in rats during
      pregnancy, 4/ the effects of phytoestrogens on reproductive processes in males of
      bilgoraj goose.

PMID- 16967097
TI  - Influence of heavy metals and 4-nonylphenol on reproductive function in fish.
AB  - Many industrial and agricultural chemicals (including heavy metals and
      alkylphenols) present in the environment have adverse effects on the reproductive
      function in fish. Three studies were conducted to assess toxicity of these
      chemicals towards reproduction of freshwater fish. It was shown that heavy metals
      added to the diets accumulate in brain tissue of carp, and this accumulation
      results in inhibition of the secretion of noradrenaline and stimulation of the
      secretion of dopamine in the hypothalamus. These processes results in a
      disturbance of hormonal equilibrium of the hypothalamo-pituitary system, which
      can unfavorably influence the efficiency of artificial spawning in fish. Quality
      of salmonid and sturgeon sperm was impaired after in vitro exposure to heavy
      metals. The degree of this toxic effect was species-specific. It was demonstrated
      that sperm motility parameters appeared to be good indicators of adverse effects
      of heavy metals fish sperm. The protection role of seminal plasma against toxic
      effects of heavy metals was suggested for salmonid fish. Oral application of 4
      nonylphenol (NP) disrupted reproduction in pikeperch. In juvenile fish a decrease
      in the percentage of males and an increase of intersex fish was observed in
      relation to dose of NP and time of exposure to this alkylphenol. Exposure of
      adult males to the NP led to the reduction in fecundity, milt quality and
      fertility.

PMID- 16967098
TI  - The influence of polychlorinated biphenyls (PCBs) and phytoestrogens in vitro on
      functioning of reproductive tract in cow.
AB  - Ovarian, endometrial and myometrial cells and strips of longitudinal myometrium
      from cows on defined days of estrous cycle were treated for 24-72 h with
      different doses (1-100 ng/ml) of PCBs mixture (Aroclor 1248) or with one of PCB
      congeners (126, 77, 153). The administered doses of PCBs neither affected the
      viability of cells nor influenced the ovarian steroidogenesis as measured by
      progesterone (P(4)), estradiol (E(2)) and testosterone secretion from luteal,
      granulosa and theca cells, respectively. In contrast, PCBs clearly inhibited a
      FSH and LH-stimulated effect on steroids secretion from granulosa and luteal
      cells. Moreover, PCBs significantly stimulated oxytocin (OT) secretion from the
      studied ovarian cells, and at least part of this effect is elicited through
      activation of glucocorticoid receptors. Further, PCBs were found to increase
      basal intracellular concentrations of Ca(2+) and both spontaneous and OT
      stimulated contractions of myometrial strips. Concomitantly, PCBs increased
      endometrial secretion of PGF(2alpha), hence the ratio of PGF(2alpha):PGE(2) was
      also increased. Phytoestrogens (genistein, daidzein, coumestrol), with a
      different intensity, reduced the effect of PCBs on PGF(2alpha) secretion and
      myometrial contractions. Genistein inhibited PCBs' effect on OT secretion from
      granulosa cells, while PCB's effect on OT release from luteal cells was reduced
      mainly by genistein and daidzein. We conclude that PCBs can impair both ovarian
      functioning and uterine contractility, while phytoestrogens are able to reduce
      this effect.

PMID- 16967099
TI  - The effect of aromatase inhibitor, fadrozole, on sGnRHa stimulated LH secretion
      in goldfish (Carassius auratus) and common carp (Cyprinus carpio).
AB  - The aromatase inhibitor, fadrozole, was applied to common carp and goldfish in
      order to examine its ability to increase the spontaneous and sGnRHa stimulated LH
      secretion. First, trials in goldfish in 2003 showed fadrozole's moderate ability
      to potentiate sGnRHa-stimulated LH secretion. However, this ability was much
      weaker than that obtained with dopamine antagonist, pimozide. There was no
      ovulation in fadrozole-treated fish. Several experiments on goldfish and carp
      during the two consecutive years with the different treatment regimes and doses
      of fadrozole did not confirm the optimistic results obtained in 2003. This shows
      that fadrozole is unable to replace the antidopaminergic drugs being used in
      fisheries practice.

PMID- 16967100
TI  - The effect of long term exposure to copper on physiological condition and
      reproduction of sheep.
AB  - The influence of copper upon some physiological parameters and reproduction in
      ewes was studied. Four groups of animals were investigated: 1/ control ewes
      (untreated); 2) ewes receiving copper as a supplement over the recommended amount
      of copper in food (10, 25 or 50 mg Cu/ewe/day); 3/ control, superovulated ewes;
      and 4) ewes treated with 50 mg copper during one month and then superovulated.
      After 10 months of daily exposure to 10 mg of copper/ewe/day no signs of toxicity
      on physiological condition and reproduction were found. In ewes exposed to 25 or
      50 mg of copper a decrease in blood parameters and increase in concentration of
      Cu in blood and liver were noticed. The wavy pattern of follicles was disturbed
      and disorders in fecundity, prolificacy and pregnancy occurred. Significant
      differences between the number of corpora lutea in superovulated control animals
      and experimental (Cu 50 mg) ewes were observed.

PMID- 16967101
TI  - Carotenoid biosynthesis in cyanobacteria: structural and evolutionary scenarios
      based on comparative genomics.
AB  - Carotenoids are widely distributed pigments in nature and their biosynthetic
      pathway has been extensively studied in various organisms. The recent access to
      the overwhelming amount genomic data of cyanobacteria has given birth to a novel
      approach called comparative genomics. The putative enzymes involved in the
      carotenoid biosynthesis among the cyanobacteria were determined by similarity
      based tools. The reconstruction of biosynthetic pathway was based on the related
      enzymes. It is interesting to find that nearly all the cyanobacteria share quite
      similar pathway to synthesize beta-carotene except for Gloeobacter violaceus PCC
      7421. The enzymes, crtE-B-P-Qb-L, involved in the upstream pathway are more
      conserved than the subsequent ones (crtW-R). In addition, many carotenoid
      synthesis enzymes exhibit diversity in structure and function. Such examples in
      the families of zeta -carotene desaturase, lycopene cylases and carotene
      ketolases were described in this article. When we mapped these crt genes to the
      cyanobacterial genomes, the crt genes showed great structural variation among
      species. All of them are dispersed on the whole chromosome in contrast to the
      linear adjacent distribution of the crt gene cluster in other eubacteria.
      Moreover, in unicellular cyanobacteria, each step of the carotenogenic pathway is
      usually catalyzed by one gene product, whereas multiple ketolase genes are found
      in filamentous cyanobacteria. Such increased numbers of crt genes and their
      correlation to the ecological adaptation were carefully discussed.

PMID- 16967102
TI  - Chimeric antibody-binding Vitreoscilla hemoglobin (VHb) mediates redox-catalysis
      reaction: new insight into the functional role of VHb.
AB  - Experimentation was initiated to explore insight into the redox-catalysis
      reaction derived from the heme prosthetic group of chimeric Vitreoscilla
      hemoglobin (VHb). Two chimeric genes encoding chimeric VHbs harboring one and two
      consecutive sequences of Fc-binding motif (Z-domain) were successfully
      constructed and expressed in E. coli strain TG1. The chimeric ZVHb and ZZVHb were
      purified to a high purity of more than 95% using IgG-Sepharose affinity
      chromatography. From surface plasmon resonance, binding affinity constants of the
      chimeric ZVHb and ZZVHb to human IgG were 9.7 x 10(7) and 49.1 x 10(7) per molar,
      respectively. More importantly, the chimeric VHbs exhibited a peroxidase-like
      activity determined by activity staining on native PAGE and dot blotting. Effects
      of pH, salt, buffer system, level of peroxidase substrate and chromogen substrate
      were determined in order to maximize the catalytic reaction. From our findings,
      the chimeric VHbs displayed their maximum peroxidase-like activity at the neutral
      pH (approximately 7.0) in the presence of high concentration (20-40 mM) of
      hydrogen peroxide. Under such conditions, the detection limit derived from the
      calibration curve was at 250 ng for the chimeric VHbs, which was approximately 5
      fold higher than that of the horseradish peroxidase. These findings reveal the
      novel functional role of Vitreoscilla hemoglobin indicating a high trend of
      feasibility for further biotechnological and medical applications.

PMID- 16967104
TI  - A basis approach to goodness-of-fit testing in recurrent event models.
AB  - A class of tests for the hypothesis that the baseline hazard function in Cox's
      proportional hazards model and for a general recurrent event model belongs to a
      parametric family C identical with {lambda(0)(.; xi): xi in Xi} is proposed.
      Finite properties of the tests are examined via simulations, while asymptotic
      properties of the tests under a contiguous sequence of local alternatives are
      studied theoretically. An application of the tests to the general recurrent event
      model, which is an extended minimal repair model admitting covariates, is
      demonstrated. In addition, two real data sets are used to illustrate the
      applicability of the proposed tests.

PMID- 16967103
TI  - Homeostatic restitution of cell membranes. Nuclear membrane lipid biogenesis and
      transport of protein from cytosol to intranuclear spaces.
AB  - Our studies on homeostatic restitution of cellular and subcellular membranes
      showed that vesicular intracellular transport is engaged in systematic and
      coordinated replacement of lipids and proteins in the membranes of the secretory,
      non-dividing epithelial cells (Slomiany et al., J. Physiol. Pharmacol. 2004; 55:
      837-860). In this report, we present evidence on the homeostatic restitution of
      lipids in the biomembranes that constitute nuclear envelopes. We investigated
      nuclear membranes lipid synthesis by employing purified intact nuclei (IN), the
      outer nuclear membrane (ONM), the inner nuclear membrane (INM) and the cell
      cytosol (CC). In contrast to Endoplasmic Reticulum (ER) which in the presence of
      CC generates new biomembrane that forms ER vesicles transporting ER products to
      Golgi, the IN, ONM and INM are not producing transport vesicles. Instead, the
      newly synthesized lipids remain in the nuclear membranes. The membranes (INM,
      ONM) of IN incubated with CC become enriched with newly synthesized
      phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylinositol
      phosphates (PIPs) and phosphatidic acid (PA). The incubation of separated ONM and
      INM with CC also enriched the membranes with IN specific lipids identified above.
      Moreover, the incubation of IN or its membranes with CC afforded retention of
      numerous CC proteins on the nuclear membrane. Here, we concentrated on 30kDa CC
      protein that displayed affinity to nuclear membrane PIP2. The 30kDa CC protein
      bound to PIP2 of IN, INM, and ONM. With IN, initially the PIP2-30kDa CC protein
      complex was detected on ONM, after 30-120 min of incubation, was found on INM and
      in nuclear contents. At the same time when the 30 kDa protein was released from
      INM and found in nuclear contents, the PIP2 of INM and ONM became undetectable,
      while the lipid extract from the membrane displaced from IN contained labeled PI
      only. Since ONM is an uninterrupted continuum of ER and INM, we speculate that
      the synthesis of the lipids in the ER, in the region adjacent to nucleus, is
      defining nuclear outer and inner biomembrane composition, is responsible for
      transport of the cytosolic protein into the nucleus and, replenishment of ER
      membrane used for vesicular transport.

PMID- 16967105
TI  - [The bioethics as a new paradigm].
AB  - The word "bioethics" is a key to understand the nature and the origins of this
      new discipline. Made up of bios and ethike (life and ethics), that it conjugates
      biology and moral in paradigmatic synthesis of science and it makes aware, facts
      and values, to be and duty to be. If there is "two cultures" that seem unable to
      speak one to the other one, science and humanities, and if this is part of the
      reason for which the future is shown so uncertain, then we should spread a
      "bridge toward the future" building the discipline of the bioethics like a bridge
      among the two cultures. To what bios and to what ethos does the the bioethics
      refer? By definition, it is biology or biomedicine and of ethics applied to the
      human behavior. The bioethics, bridge toward the future and among the two
      cultures, he or she responds to the challenge of the crisis bioethics of the
      technological era, crisis at the same time vital and normative in whose warp
      stands out the ecological catastrophe, the new biology and the medicalization of
      the life.

PMID- 16967106
TI  - [Work environment and train conductors' restlessness. Impact on workers' health].
AB  - In this work, which follows a quali-quantitative methodology, we explored train
      conductors' sources of restlessness and the relationship between work environment
      stressors and health of those conductors from urban zones. Firstly, observations
      and interviews to key informants and conductors were done. Secondly, a group of
      conductors were asked to complete the following instruments: Occupational Stress
      Inventory (OSI, Osipow and Spokane, 1987; adaptation: Schmidt, Leibovich,
      Schufer, Gonzalez and Marcomi, 2003), General Health Questionnaire (GHQ, Goldberg
      and Williams, 1996; Spanish version: Lobo and Munoz, 1996) and a Socio
      demographic and a Work Questionnaire (elaborated by researcher group). Data were
      analyzed with quali-quantitative methodology. Main sources of restlessness from
      this population were identified as well as the possible impact these sources have
      on workers health.

PMID- 16967107
TI  - [Psychogeriatric unit within a General Hospital. Descriptive analysis of
      outpatient assessment, diagnosis and treatment].
AB  - OBJECTIVE: To assess the frequency of some epidemiological variables in 200
      patients over 65 years old that came to admission as outpatients in the
      psychogeriatric area in the psychiatric unit at the Hospital Italiano in Buenos
      Aires, Argentina. METHOD: A specific questionnaire was completed by both patient
      (or relative) and the physician. RESULTS: 83% were female and 17% male. The most
      important diagnosis were depressive disorder (34%), adaptive upheavals (28%) and
      dementia (16%), within this group, major depressive disorder and Alzheimer
      dementia. Only a 31% patients went under a neuropsychological assessment
      psychotherapy was indicated to 18% of the patients, pharmacology for 39%, memory
      improvement group for 18% and combined treatment for 25%. CONCLUSION: This paper
      brings data regarding outpatients over 65 years old with psychogeriatric
      treatment. This may improve the health system in psychogeriatric area taking into
      account socio-cultural and economic factors.

PMID- 16967108
TI  - [Clinical aspects of collaborative treatments between psychiatrists and
      psychotherapists].
AB  - The present paper analyzes the combination of psychiatric and psychological
      treatments, exploring the clinical aspects that turn them into split or
      collaborative treatments. A historical sketch is presented and the current state
      of the psychiatrist-psychotherapist relationship is depicted, putting special
      emphasis on the frequent causes of tension usually hard to resolve. Two case
      vignettes are put forward to shed light on how combined treatments are much more
      than a simple addition of medication and psychotherapy, including subtle and
      complex aspects of both professionals work and a particular relationship between
      them.

PMID- 16967109
TI  - [Psychiatry and psychoanalysis: a crazy dialogue].
AB  - The relation between psychiatry and psychoanalysis has been and is complex and
      fertile, in the frame of coincidences and differences. The common sense will be
      the first point that will allow us to guide the reflection. The hermeneutic
      treatment of the sense and its opposite, the non sense, will open the way for
      enquiring a diversity of concepts: 1. A different use of the word. 2. The
      consequent destination between two ways of the truth. 3. It is extracted from the
      previous point two positions that I call: psychiatric volunteer and the
      psychoanalyst's desire. At the end of the article, we explore different
      positions, but not necessarily incompatible, referred to the suicide act risk.

PMID- 16967110
TI  - [Collaborative relationship between psychiatrists and psychologists: a literature
      review].
AB  - The aim of this paper is to review the empirical literature concerning the
      collaborative relationship between psychiatrists and psychologists. Despite the
      scarcity of published studies about this topic, three main areas of interest
      could be identified: 1. Literature regarding combined treatments (psychotherapy
      plus medication); 2. The development of therapeutic programs for specific
      conditions within a biopsychosocial framework; 3. The discussion about the team
      role in the approach of difficult cases. In general terms, it could be stated
      that collaborative treatments are a valid and effective option in mental health
      settings.

PMID- 16967111
TI  - [Pharmacotherapy as psychotherapy?].
AB  - If the psychotherapist considers the psychological implications of the
      medication, he can develop very important interventions for the result of the
      treatment. Diverse examples in that sense are offered. Like a symbol, a metaphor
      and a rite, the medication can be used much more than which it usually does. More
      than a parallel treatment, it is a material with which a central part of
      psychotherapy can be constructed.

PMID- 16967112
TI  - [The possibility of an interdisciplinary work].
AB  - It is a fact that several disciplines take part in the treatment of specific
      pathologies. The approach to alimentary disorders, for example, gathers
      psychiatrists, clinicians, dieticians and psychotherapists. However, despite that
      many disciplines may work together that does not mean that a true
      interdisciplinary task is being performed, specially if we consider it as
      something different from an effort to achieve a complementary relationship. From
      a psychoanalytic standpoint we question the meaning of interdisciplinary work.

PMID- 16967113
TI  - The application of modified mesoporous silicas in liquid phase catalysis.
AB  - This review focuses on recent developments in the preparation, properties and
      catalytic applications of chemically modified mesoporous silicas. Over the last
      few years, this group of materials has been the subject of intense activity in
      the materials community, and many applications have been found for these
      fascinating materials. This non-exhaustive review aims to highlight the key
      features of the materials, which are relevant and important to catalysis, and
      illustrates their utility with a series of recent examples.

PMID- 16967114
TI  - Bulky 4-phosphacyclohexanones: diastereoselective complexations,
      orthometallations and unprecedented [3.1.1]metallabicycles.
AB  - The 4-phosphacyclohexanones, 2,2,6,6-tetramethyl-1-phenyl-4-phosphorinanone (La),
      1,2,6-triphenyl-4-phosphorinanone ((Ph)Lb), 1-cyclohexyl-2,6-diphenyl-4
      phosphorinanone ((Cy)Lb) and 1-tert-butyl-2,6-diphenyl-4-phosphorinanone ((Bu)Lb)
      have been made by modifications of literature methods. Phosphines (R)Lb are each
      formed as mixtures of meso- and rac-diastereoisomers. Isomerically pure rac
      (Ph)Lb, rac-(Cy)Lb and meso-(Bu)Lb can be isolated by recrystallisation from
      MeCN. Heating mixtures of isomers of (R)Lb with TsOH leads to isomerisations to
      give predominantly the meso-(R)Lb. The complex trans-[PdCl2(La)2] (1) is readily
      made from [PdCl2(NCPh)2] but the analogous platinum complex 2 has not been
      detected and instead, cyclometallation at the 3-position (alpha to the ketone) in
      the phosphacycle occurs to give trans-[PtCl(La)(La-3H)] (3) (where La-3H = La
      deprotonated at the 3-position) featuring a [3.1.1]metallabicycle as confirmed by
      X-ray crystallography. The analogous palladabicycle 4 has been detected upon
      treatment of 1 with Et3N in refluxing toluene. The type of complex formed by
      (R)Lb depends on which diastereoisomer (meso or rac) is involved. rac-(Ph)Lb (a
      mixture of R,R- and S,S-enantiomers, labelled alpha and beta) forms trans
      [MCl2(rac-(Ph)Lb)2], M = Pd (5) or Pt (6), as mixtures of diastereoisomers
      (alphaalpha/betabeta and alphabeta forms). The structure of alphaalpha-6 has been
      determined by X-ray crystallography. Ligand competition experiments monitored by
      31P NMR showed that Pd(II) and Pt(II) have a significant preference to bind rac
      (Ph)Lb over meso-(Ph)Lb. meso-(Bu)Lb reacts with [PtCl2(NCBu(t))2] under ambient
      conditions to give the binuclear complex [Pt2Cl2(meso-(Bu)Lb-2'H)2] (7) where
      orthometallation has occurred on one of the exocyclic phenyl substituents as
      confirmed by X-ray crystallography. rac-(Bu)Lb reacts with [PtCl2(NCBu(t))2] to
      give a mononuclear cyclometallated species assigned the structure trans-[PtCl(rac
      (Bu)Lb-2'H)((Bu)Lb)] (8) on the basis of its 31P NMR spectrum. rac-(Cy)Lb reacts
      with [PtCl2(NCBu(t))2] in refluxing toluene to give trans-[PtCl2(rac-(Cy)Lb)2]
      (9) and the crystal structure of alphabeta-9 has been determined.

PMID- 16967115
TI  - Stability of phosphinidenes--are they synthetically accessible?
AB  - The relative stability of different singlet phosphinidenes (R-P) has been
      investigated by using isodesmic reactions. The energies of these reactions with
      several R groups were calculated with DFT and ab initio methods at different
      levels of theory. The best stabilising effect on the phosphinidene centre is
      exhibited by the R'2C=N-group, resulting in a singlet ground state. The analysis
      of the electron density in the parent H2C=N-P, indicates a considerable double
      bond character of the PN bond. Further tuning of the C=N pi-bond polarity is
      possible by variation of the R' substituents. Using trimethylsilyl substituents
      or incorporating the carbon atom in a pi-withdrawing pentafulvene ring the
      stabilization and the computed singlet triplet separation increases. The
      thermodynamics and the kinetics of dimerisation reactions of the most stabilised
      R'2C=N-P indicates that these compounds are likely synthetic targets.

PMID- 16967116
TI  - The reaction of TiF4 with Li(OC(CF3)2Ph): direct synthetic route to the lithium
      titanium heterometallic fluoride bridged complex {Li(THF)2TiF3(OC(CF3)2Ph)2}2 and
      Ti(OC(CF3)2Ph)4 alkoxide.
AB  - Reaction of TiF4 and LiORf (Rf = C(CF3)2Ph) in the donor solvent-THF lead to the
      isolation of the heterometallic lithium-titanium complex (THF)2Li(mu
      F)2Ti(ORf)2(mu-F)2Ti(ORf)(2)(mu-F)2Li(THF)2 (1) and Ti(ORf)4 alkoxide (2).
      Interaction of TiF4 and LiORf in the non-coordinating and low polar toluene
      yielded only Ti(ORf)4 (2). Compounds 1 and 2 were characterized by X-ray single
      crystal analysis, IR, NMR and mass spectrometry. Compound 1 is a centrosymmetric
      fluorine bridged dimer and contains the Li(mu-F)2Ti(mu-F)2Ti(mu-F)2Li cage.
      Complex 2 containing four bulky ligands is monomeric. NMR evidence is presented
      that the TiF4 and LiORf in THF solution gave lithium-titanium heterometallic
      complexes containing Li-(mu-F)-Ti and the Ti-(mu-F)-Ti bonds.

PMID- 16967117
TI  - Synthesis and characterization of Pd and Pt complexes of 1,3
      bis(ferrocenylchalcogeno)propanes: crystal structures of FcSe(CH2)3SeFc and
      [M{FcE(CH2)3E'Fc}2](PF6)2 (M = Pd, Pt; E, E' = Se, Te; Fc = [Fe(eta5-C5H5)(eta5
      C5H4)]).
AB  - Reaction of a 1,3-bis(ferrocenylchalcogeno)propane, FcE(CH2)3E'Fc (L: E, E' = Se
      or Te; Fc = [Fe(eta5-C5H5)(eta5-C5H4)]), with a palladium(II) or platinum(II)
      precursor [M(NCMe)4](PF6)2 (M = Pd or Pt) in acetonitrile at room temperature led
      in good yield to the bis-chelate complexes [ML2](PF6)2. The structures of
      FcSe(CH2)3SeFc and all six complexes have been determined by X-ray
      crystallography. Electrochemical studies showed that electronic communication
      between ferrocenyl groups, absent in all three bis(ferrocenylchalcogeno)propanes,
      is established on complexation only for E = Se and E' = Se or Te, when the
      through-bond Fe...Fe distance is reduced to 13.17 A or less.

PMID- 16967118
TI  - Tris(1,2-dimethyl-3-hydroxy-4(1H)-pyridone)oxotantalum(v): a new water-soluble
      tantalum complex containing the [Ta=O]3+ core.
AB  - The synthesis, the characterization and the X-ray crystal structure of a novel
      tantalum(v) complex tris(1,2-dimethyl-3-hydroxy-4(1H)-pyridone)oxotantalum(v)
      [TaO(C7H8O2N)3] 1 is reported. Starting from the tantalum pentaethoxide a two
      step reaction was carried out observing rigorous anhydrous conditions in methanol
      in the first step, while the insertion of the oxo group was achieved using water
      as oxygen donor in the second step. X-Ray diffraction analysis of a crystal of 1
      obtained upon evaporation of an aqueous solution shows a seven-coordinate
      monomeric complex containing the [Ta=O]3+ core in the triclinic space group P1, a
      = 7.282(3), b = 14.055(5), c = 16.987(6) A, alpha = 65.704(5), beta = 89.155(6),
      gamma = 75.270(6) degrees, V = 1525(1)A3, Z = 2. Spectroscopic investigation
      reveals that the complex is highly soluble and stable in water at physiological
      pH values; as a consequence the complex may represent a potential candidate for
      the development of new studies on aqueous tantalum(v) chemistry for
      radiopharmaceutical applications.

PMID- 16967119
TI  - Novel dimetal bridging carbene complexes derived from a terminal carbonyl dimetal
      compound. Syntheses, structures and reactivities of 7H-indene-coordinated diiron
      bridging carbene complexes.
AB  - Pentacarbonyl-7H-indenediiron, [Fe2(CO)5(eta3,eta5-C9H8)] (1), reacts with
      aryllithium, ArLi (Ar = C6H5, p-C6H5C6H4), followed by alkylation with Et3OBF4 to
      give novel 7H-indene-coordinated diiron bridging alkoxycarbene complexes [Fe2{mu
      C(OC2H5)Ar}(CO)4(eta4,eta4-C9H8)] (2, Ar = C6H5; 3, Ar = p-C6H5C6H4). Complexes 2
      and 3 react with HBF4.Et2O at low temperature to yield cationic bridging carbyne
      complexes [Fe2(mu-CAr)(CO)4(eta4,eta4-C9H8)]BF4 (4, Ar = C6H5; 5, Ar = p
      C6H5C6H4). Cationic 4 and 5 react with NaBH4 in THF at low temperature to afford
      diiron bridging arylcarbene complexes [Fe2{mu-C(H)Ar}(CO)4(eta4,eta4-C9H8)] (6,
      Ar = C6H5; 7, Ar = p-C6H5C6H4). The similar reactions of 4 and 5 with NaSC6H4CH3
      p produce the bridging arylthiocarbene complexes [Fe2{mu-C(Ar)SC6H4CH3
      p}(CO)4(eta4,eta4-C9H8)] (8, Ar = C6H5; 9, Ar = p-C6H5C6H4). Cationic 4 and 5 can
      also react with anionic carbonylmetal compounds Na[M(CO)5(CN)] (M = Cr, Mo, W) to
      give the diiron bridging aryl(pentacarbonylcyanometal)carbene complexes [Fe2{mu
      C(Ar)NCM(CO)5}(CO)4(eta4,eta4-C9H8)] (10, Ar = C6H5, M = Cr; 11, Ar = p-C6H5C6H4,
      M = Cr; 12, Ar = C6H5, M = Mo; 13, Ar = p-C6H5C6H4, M = Mo; 14, Ar = C6H5, M = W;
      15, Ar = p-C6H5C6H4, M = W). Interestingly, in CH2Cl2 solution at room
      temperature complexes 10-15 were transformed into the isomerized 7H-indene
      coordinated monoiron complexes [Fe(CO)2(eta5-C9H8)C(Ar)NCM(CO)5] (16, Ar = C6H5,
      M = Cr; 17, Ar = p-C6H5C6H4, M = Cr; 18, Ar = C6H5, M = Mo; 19, Ar = p-C6H5C6H4,
      M = Mo; 20, Ar = C6H5, M = W; 21, Ar = p-C6H5C6H4, M = W), while complex 3 was
      converted into a novel ring addition product [Fe2{C(OC2H5)C6H4C6H5-p-(eta2,eta5
      C9H8)}(CO)5] (22) under the same conditions. The structures of complexes 2, 6, 8,
      14, 18 and 22 have been established by X-ray diffraction studies.

PMID- 16967120
TI  - Design of new heteroscorpionate ligands and their coordinative ability toward
      Group 4 transition metals; an efficient synthetic route to obtain enantiopure
      ligands.
AB  - The reaction of different types of bis(pyrazol-1-yl)methane derivatives with
      Bu(n)Li and alkyl or aryl-containing-isocyanates or isothiocyanates, some of
      these as chiral reagents, gives rise to the preparation of new heteroscorpionate
      ligands in the form of the lithium derivatives [Li(NNE)]2 (1-10), although a
      similar process with trimethylsilyl isocyanate or isothiocyanate gave the
      complexes [Li(NCX)(bdmpzs)(THF)](X = O, 11; X = S, 12)[bdmpzs = bis(3,5
      dimethylpyrazol-1-yl)trimethylsilylmethane]. Compounds 1-8 reacted with
      [TiCl4(THF)2] or [MCl4](M = Zr, Hf) to give a series of cationic complexes
      [MCl3{kappa3-NNE(H)}]Cl (13-36) where the heteroscorpionate ligand contains
      either an acetamide or thioacetamide group resulting from the protonation of the
      corresponding acetamidate or thioacetamidate. However, under appropriate
      experimental conditions neutral Ti complexes were isolated-namely [TiClx(NMe2)3
      x(S-mbbpam)](37-39)[S-mbbpam =(S)-(-)-N-alpha-methylbenzyl-2,2-bis(3,5
      dimethylpyrazol-1-yl)acetamidate]. Finally, two alkoxide-containing titanium
      complexes [TiClx(OR)3-x(S-mbbpamH)]Cl (40-41) were also prepared. The structures
      of these complexes have been determined by spectroscopic methods and, in
      addition, the X-ray crystal structures of 1, 12, and 19 were also established.

PMID- 16967121
TI  - Base induced P-C bond cleavage in a coordinated bis(dimethylphosphino)methane
      ligand.
AB  - Treatment of fac-[Mn(CNR)(CO)3{(PMe2)2CH2}]ClO4 (1a R = Ph, R = tBu) with KOH
      produced the cleavage of one of the P-C bonds of the coordinated dmpm ligand,
      resulting in the formation of phosphine-phosphinite complexes fac
      [Mn(PMe2O)(CNR)(CO)3(PMe3)] (2a,b). Alkoxides such as NaOMe and NaOEt promoted
      similar processes in 1a,b, yielding fac-[Mn(CNR)(CO)3(PMe3)(PMe2OR')]ClO4 (3a R =
      tBu, R' = Me; 3b R = Ph, R' = Me; 4a R = tBu, R' = Et; 4b R = Ph, R' = Et)
      derivatives. The phosphinite ligand in 2a, b can be sequentially protonated by
      addition of 0.5 and 1 equivalent of HBF4 leading to fac
      [{Mn(CNR)(CO)3(PMe3)(PMe2O)}2H]BF4 (6a,b) and fac-[Mn(CNR)(CO)3(PMe3)(PMe2OH)]BF4
      (5a,b), respectively.

PMID- 16967122
TI  - Effect of Sr content on the crystal structure and electrical properties of the
      system La2-xSrxNiO4+delta (0 <or=x<or= 1).
AB  - Materials formulated as La(2-x)Sr(x)NiO(4+delta) (0 <or=x<or= 1) have been
      prepared and investigated by high-resolution neutron powder diffraction in order
      to correlate the structural variation induced by the incorporation of Sr into the
      crystal lattice with the electronic and thermal properties of each material. The
      evolution of the electrical conductivity and thermal expansion coefficients with
      temperature have been determined in order to study the potential use of these
      compounds as cathodes for intermediate-temperature solid oxide fuel cells (IT
      SOFC). These oxides show a good thermal expansion coefficient (TEC = 11-13 x 10(
      6) K(-1)), and high electronic conductivity up to 273 S cm(-1). It is noticeable
      that a great enhancement of the electrical conductivity with the Sr content is
      concomitant with the shortening of the Ni-O1 bond length.

PMID- 16967123
TI  - Coordination ability of trans-cyclohexane-1,2-diamine-N,N,N',N'
      tetrakis(methylenephosphonic acid) towards lanthanide(III) ions.
AB  - The proton and metal complex equilibria of trans-cyclohexane-1,2-diamine
      N,N,N',N'-tetrakis(methylenephosphonic acid) (CDTP) with lanthanide(iii) ions,
      where Ln(III) = La(III), Nd(III), Sm(III), Eu(III), Gd(III), Tb(III), Ho(III) and
      Lu(III) were studied. The stoichiometry, protonation and complex formation
      constants were determined by potentiometric titration at 25.0 degrees C and ionic
      strength of 0.1 mol dm(-3) (KCl). All metal ions form several species: [LnH4L]-,
      [LnH3L](2-), [LnH2L](3-), [LnHL](4-), [LnL](5-), [LnH(-1)L](6-) and [LnH(-2)L](7
      ) in the pH range between 2 and 11. The stability constants log beta(LnL) were
      found to be between 14.7 and 16.7. The studied complexes were also characterized
      by spectroscopic methods (31P NMR, UV-Vis absorption and emission spectroscopy).
      These studies allowed to reveal a distinct structural change of the Ln(III)-CDTP
      complex which occurs between protonated and hydroxy species in solutions at pH
      around 7.5. The major change is caused by the involvement of both nitrogen donors
      in the metal ion coordination occurring in ML species. The data obtained from UV
      Vis spectroscopy allowed to draw conclusions about complex symmetry and to
      estimate a number of coordinated water molecules. The hydration number or more
      precisely the number of two OH oscillators was found to be approximately one in
      all species formed over the pH range between 5 and 10. The structure of the major
      hydroxy complex was supported by X-ray crystallographic data. The crystal
      structures of the Eu(III) and Tb(III) complexes clearly show that the CDTP ligand
      is coordinated to the Ln(III) ion by two nitrogen and four oxygen atoms in such a
      way that only one oxygen atom from each phosphonic group is placed in the
      lanthanide inner sphere. The monomeric complex anion is connected to a symmetry
      related ion through short hydrogen bonds formed by two hydroxy ions and one water
      molecule. In this way the two neighbouring anions form a quasi-dimer in which one
      of the Ln(III) ion is seven-coordinate (two N atoms, four O atoms and one hydroxy
      ion) and the other is eight-coordinate (two N atoms, four O atoms, one hydroxy
      ion and one water molecule).

PMID- 16967124
TI  - Dicatechol cis-dioxomolybdenum(VI): a building block for a lithium cation
      templated monomer-dimer equilibrium.
AB  - Dinuclear helicate-type complexes form from 3-carbonyl catechol derivatives and
      MoO2 units. The two monomeric subunits are non-covalently bound through
      templating Li+ ions. The monomeric and dimeric complexes as well as a hydrolysis
      product have been investigated in the solid state by X-ray crystallography, in
      solution by NMR experiments, and in the gas phase by ESI mass spectrometry.
      Dimerization constants can easily be extracted from NMR experiments. A particular
      property of these complexes is the mutual homochiral recognition between the two
      halves of the dimers which only occurs between homochiral monomers.

PMID- 16967126
TI  - [Clinical research conducted by medical students: its potential for learning and
      the national scientific production].

PMID- 16967127
TI  - [Quality of life in coronary arterial diseases carriers].

PMID- 16967128
TI  - [Pre-Eclampsia : "hypovolemic state" or "content adjusted to the continent" ?].

PMID- 16967129
TI  - [Roux en Y gastric bypass surgery or gastric band to the treatment of the morbid
      obesity?].

PMID- 16967130
TI  - [Which the number of diabetic patients type 2 necessary to treat to prevent a
      coronary event ?].

PMID- 16967131
TI  - [Gynecomastia in adults: only esthetics ?].

PMID- 16967132
TI  - [Triage to the identification of alcohol harmful use in the primary health care].

PMID- 16967133
TI  - [Update in the treatment of acute otitis media in childhood , evidence-based and
      patient-centered].

PMID- 16967134
TI  - [Isolated effect of the monoclonal antibody trastuzumab (Herceptin) in a patient
      with local recurrence of breast carcinoma with HER-2 hyperexpression. ].

PMID- 16967135
TI  - [Postoperative adverse effects in gynaecological and breast surgeries].
AB  - OBJECTIVES: To analyze the occurrence of adverse effects in the first 24-hour
      postoperative/postanesthetic period in women undergoing minor gynecologic or
      minor breast surgeries and to identify main associated factors. METHODS: A cross
      sectional study was conducted with 159 women who underwent minor gynecologic or
      breast surgeries. The women were admitted to the hospital one day before surgery
      and remained hospitalized for at least 24 hours after surgery. The anesthetic
      techniques performed were intercostal nerve blockade, spinal anesthesia, and
      general anesthesia. RESULTS: The most frequent adverse effects were vomiting,
      nausea and pain that occurred in 40.3% of women. Of these effects, 60% were
      observed in the first four hours and 80% were observed in up to six hours after
      surgical intervention. Women submitted to intercostal blockade received earlier
      postanesthetic release. Spinal anesthesia was most frequently associated with
      postoperative pain, although with a lower incidence of nausea and vomiting when
      compared to general anesthesia and intercostal blockade. The incidence of pain
      was higher in women who smoked. CONCLUSIONS: A six-hour period of postoperative
      observation appeared to be adequate for assessment of most complications and
      adverse effects occurring in women who undergo minor gynecologic or minor breast
      surgeries.

PMID- 16967136
TI  - [Laparoscopic adrenalectomy: a prospective study comparing transperitoneal and
      retroperitoneal approaches].
AB  - OBJECTIVES: A prospective protocol was used to compare transperitoneal and
      retroperitoneal laparoscopic access for treatment of adrenal lesions. METHODS:
      Forty patients (19 male and 21 female) were submitted to laparoscopic
      adrenalectomy. Patients were operated by two surgeons. Twenty cases for each type
      of access (transperitoneal and retroperitoneal) were selected for analysis.
      Operative time, blood loss, time to oral intake, dose of analgesic, surgical
      complications, conversions, hospital stay and return to normal activities were
      compared for both approaches. RESULTS: All procedures were successfully
      completed. Operative mean time and time to oral intake were 3.6 h and 24 h for
      the transperitoneal and 2.5 h and 12 h for the retroperitoneal approach (p<0.05).
      There were no differences in blood loss, analgesia, hospital stay and time for
      return to normal activities. Complications were observed in two patients in the
      transperitoneal approach (retroperitoneal bleeding and pancreatitis) and there
      were three events in the retroperitoneal approach (hipercarbia, peritoneal
      laceration and pneumonia). No conversions occurred in this cohort of patients.
      CONCLUSION: Laparoscopic adrenalectomy is a safe and efficient treatment for an
      adrenal mass of up to 10 cm. There are no relevant differences between the
      transperitoneal and retroperitoneal approach. Choice of the laparoscopic approach
      rests upon particular aspects of each case or upon the surgeon's preference.

PMID- 16967137
TI  - [Nutritional status and related factors among elderly Brazilians].
AB  - OBJECTIVE: This study describes the nutritional status and associated factors
      among elderly Brazilians. METHODS: Data from "Pesquisa sobre Padroes de Vida"
      (PPV- Life Pattern Research), conducted by the "Brazilian Geographic and
      Statistics Institute" in 1996/1997 were used. Body Mass Index (BMI) was applied
      to classify nutritional status and is the response variable of this study.
      Multivariate analysis with polytomous logistic regression was used. RESULTS:
      Prevalence of underweight was 5.7%, eutrophy 50.4%, overweight 32.3% and obesity
      11.6%. Women have a 1.32 greater chance of overweight (CI 95% 0.99-1.74; p=0.05)
      and 4.11 of obesity (CI 95% 2.57-6.57; p<0.01). Higher age increased risk of
      underweight and diminished that of overweight and obesity. Elderly with a lower
      income have a higher risk of underweight and those with a greater income have
      higher risk of overweight and obesity. Elderly with a chronic disease have a
      higher risk of changes in the nutritional status. CONCLUSION: Results show a
      higher prevalence of overweight and eutrophy and a lower prevalence of obesity
      and underweight. Characteristics associated with nutritional status other than
      eutrophy are: gender, schooling, income, chronic health problem and age.

PMID- 16967139
TI  - [Tetanus in the climacterium].
AB  - OBJECTIVE: The purpose of this study was to evaluate Brazilian women in the
      climacterium who are affected by tetanus. METHODS: Data were collected from
      publications of DATASUS/Ministerio da Saude (Health Ministry) referring to
      hospital admissions (SIH) in hospitals of the Sistema Unico de Saude (SUS)
      (Official Health System) and accorded hospitals. The numbers of vaccinations
      administered were obtained at the National Program of immunizations. Data
      regarding the population was obtained at the Brazilian Geography and Statistics
      Institute (IBGE). RESULTS: Between January 2001 and July 2004, while for the male
      gender, with the passing of years there was reduction in the total number of
      admissions due to tetanus, for the female gender there was an increase. Frequency
      of the disease, for both genders aged from 35 to 64 years in the different
      regions of Brazil, disclosed that the there is a higher incidence in the
      Northeast, followed by the Southeast and South. Data for the year 2002 showed
      that in the age bracket from 50 to 59 years, only 15.73% of the people were
      adequately protected against tetanus. CONCLUSIONS: In the adult phase, healthy
      life depends on public health policies, in the sense of supplying appropriate
      prevention against the disease. In the case of tetanus, vaccination is an
      effective prevention.

PMID- 16967138
TI  - [Evaluation of clinical and psychiatric symptoms in sub clinical hypothyroidism].
AB  - BACKGROUND: This investigation evaluated and correlated clinical, laboratorial
      aspects and psychiatric symptoms in sub clinical hypothyroidism (SH). METHODS:
      Cross sectional study involving 103 patients with SH and 60 subjects without
      thyroid disease. Clinical and psychiatric evaluation was respectively based on
      the Zulewski score and Hamilton A, Hamilton D and Beck questionnaires. Serum
      thyreotropin (TSH), (thyroxine) FT4 and (antithyroperoxidase) ATPO were measured
      in all participants. Analysis of continuums data was assessed by the Student t-
      test, for normally distributed data, and by the Mann- Whitney and Kruskal Wallis
      tests for non-parametric data. The chi2, Fisher's and Kruskal Wallis tests were
      used to study qualitative variables. Multivariate analyses were used to study
      confounding variables. RESULTS: Mean serum TSH level was 7.76 +/- 2.9 micro UI/mL
      in SH and 1.66 +/- 0.6 micro UI/mL in the group without thyroid disease
      (p=0.001). Mean serum T4L was slightly lower among patients with HS, and showed a
      negative linear correlation with TSH. Higher frequencies of abnormal clinical
      score (48.3 vs. 67.0%; p=0.02), depression self reported symptoms (20.5 vs.
      44.2%; p=0.011) and anxiety symptoms (86.0 vs. 63.4%; p=0.004) occurred more
      frequently in SH. Frequency of psychiatric symptoms had a positive correlation
      with the clinical score and serum TSH. There was no association between the
      clinical and psychiatric findings and the etiology of SH, presence of ATPO, age
      or menopause. CONCLUSIONS: The study showed that SH was associated with clinical
      findings and with psychiatric symptoms. Clinical trials are required to evaluate
      possible improvement with levotiroxine.

PMID- 16967140
TI  - Fetal rhd genotyping from maternal plasma in a population with a highly diverse
      ethnic background.
AB  - OBJECTIVE: To establish the performance of conventional PCR as a noninvasive
      method for fetal genotyping, by free fetal DNA analysis of distinct RHD regions
      from maternal plasma, in a population of a diverse ethnic origin. METHODS: We
      conducted a validity of the diagnostic test by analyzing 81 plasma samples from
      RhD-negative Brazilian pregnant women, from 4 to 41 gestational weeks. We tested
      for exon 10 and intron 4 gene regions by allele specific-PCR. Fetal RHD
      genotyping by PCR on maternal plasma was compared to serologic RhD typing in the
      neonatal period. RESULTS: Samples were obtained as follows: 15 in the 1st, 37 in
      the 2nd and 29 in the 3rd trimester. General accuracy was 97.3%, sensitivity of
      98.3% and specificity of 93.8%. CONCLUSIONS: Conventional PCR is an accurate
      method for fetal RHD genotyping on maternal plasma, even in a population of mixed
      ethnic origin.

PMID- 16967141
TI  - [Quality of life in patients with coronary artery disease: comparison between the
      genders].
AB  - OBJECTIVE: To analyze the quality of life of people with coronary artery disease
      (CAD) who underwent distinct therapeutic interventions and compare the possible
      differences between genders. METHODS: This study comprised 542 subjects, 376 men
      (58.5 +/- 8.7 years) and 166 women (61.8 +/- 9.2 years), with CAD who underwent
      surgical, medical treatment or angioplasty. Quality of life was assessed with The
      Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) administered at
      the beginning of treatment and after 6 and 12 months. The applied statistical
      method was the ANOVA test. RESULTS: Those who underwent surgical treatment had
      scores of 46, 63, 68, for physical components; 52, 65, 62 for medical treatment,
      and 57, 66, 70 for angioplasty, respectively, in the initial, six, and twelve
      months phases. For mental components, results were 58, 71, 74 for the surgical
      intervention; 61, 69, 69 for the medical treatment, 64, 74, 74 for angioplasty.
      The differences over time and between treatments reached a statistical
      significance (p<0.001). In comparing genders, physical component scores in men
      were 56*, 69, 77*, and 41*, 64, 62* in women, respectively; mental component
      scores in men were 61*, 73, 80* and 51*, 68, 62* in women (*p<0.0001).
      CONCLUSIONS: Subjects who underwent surgical treatment had the most favorable
      evolution. Men when compared to women had a better quality of life in the
      beginning of treatment with a progressive improvement after six and twelve
      months, while women, after an improvement at six months, presented a decrease at
      twelve.

PMID- 16967142
TI  - [Habitual physical activity and cardiovascular risk in post menopause].
AB  - BACKGROUND: To evaluate the prevalence of habitual physical activity and
      cardiovascular risk in postmenopausal women. METHODS: A cross-sectional study was
      made of 162 women, aged 40-65 years, amenorrheic for at least 12 months,
      receiving care at the menopause clinic of CAISM/UNICAMP. The women verbally
      answered the International Physical Activity Questionnaire for assessment of
      physical activity levels. This instrument evaluates the frequency and duration of
      activities performed during transportation, at work, at home or in leisure- over
      the course of a normal week. Women were classified as sedentary, insufficiently
      active, active or very active. Laboratory tests were carried out to measure total
      serum cholesterol, high density lipoproteins and fasting glucose. Systolic and
      diastolic pressure was measured. RESULTS: The mean age of women in this study was
      56.5 years and mean age at menopause was 46 years. Prevalence of physical
      activity was 83.3% of which 80.8% were classified as active, 2.5% as very active
      and 16.7% as insufficiently active. Principal activities were performed during
      transportation and while carrying out household chores. Only 38.3% of women had
      leisure-time physical activities. In the population, 87.7% of the women presented
      a Framingham score <10, considered of low cardiovascular risk. CONCLUSIONS:
      Postmenopausal women show a high prevalence of habitual physical activity and low
      adherence to physical exercise. Cardiovascular risk was low in the population
      studied. It is important to encourage these women to practice physical activity
      compatible with their physical condition, to orient and stimulate them to
      practice not only their habitual physical activity but also physical exercise.

PMID- 16967143
TI  - [Hysterosonography: evaluation of the uterine cavity in women with abnormal
      uterine bleeding].
AB  - OBJECTIVE: To compare the diagnostic accuracy of sonohysterography with that of
      hysteroscopy and ultrasonography for the diagnosis of uterine alterations with
      abnormal uterine bleeding. METHODS: Fifty three patients scheduled for
      hysteroscopy at the Hysteroscopy Sector of the Women's Hospital (CAISM) at the
      "Universidade Estadual de Campinas" (Brazil) were included in the study.
      Sensitivity and specificity of the three propaedeutic methods were compared using
      histology as the gold standard. RESULTS: Sensitivity of sonohysterography and of
      hysteroscopy was 94% and that of ultrasonography 83%. The specificity of
      sonohysterography was 77%, of hysteroscopy 91% and of ultrasonography 69%. There
      were no significant differences between sensitivities of the three methods.
      However, a significant difference was found between the specificity of
      ultrasonography and hysteroscopy. Sonohysterography demonstrated a much greater
      capability than ultrasonography to identify endometrial polyps. CONCLUSION:
      Sonohysterography may be used to complement ultrasonography and to substitute
      hysteroscopy, for the diagnosis of alterations that result in abnormal uterine
      bleeding.

PMID- 16967144
TI  - [New formulation of sublingual misoprostol (25 mcg) for induction of labor].
AB  - OBJECTIVES: To determine effectiveness and safety of sublingual misoprostol in
      tablets of 25 mcg, given every 6 hours for induction of labor in high-risk
      pregnant women hospitalized in two teaching hospitals in the Northeast of Brazil.
      METHODS: An open, non-randomized clinical trial was conducted, including 40 women
      with high-risk pregnancies hospitalized at "Maternidade-Escola Assis
      Chateaubriand" and "Instituto Materno-Infantil de Pernambuco". All of them had
      gestational age >or= 37 weeks, alive fetus with good vitality and Bishop scores
      <or= 7. A tablet of 25 mcg of misoprostol was administered every 6 hours, up to a
      maximum of 4, until active labor. Statistical analysis was performed using the
      public domain software Epi-Info 3.2.2. RESULTS: Active labor occurred in 100% of
      cases after misoprostol administration. The mean (+/-SD) induction-to-labor
      interval was 4.8(+/-3.8 hours. Interval from induction-to-delivery varied from 8
      to 31 hours with 95% of the deliveries occurring in the first 24 hours with 75%
      of vaginal deliveries. The frequency of tachysystole was 12.5%. The women did not
      present relevant side effects neither were there any neonatal complications.
      CONCLUSIONS: The sublingual tablet of misoprostol of 25 mcg was shown to be
      effective for induction of labor in high-risk pregnant women. The efficacy and
      acceptability of this new route should be compared to vaginal administration of
      misoprostol in future prospective randomized clinical trials.

PMID- 16967145
TI  - [Factors related to frequency of sexual activity of postmenopausal women].
AB  - OBJECTIVE: To identify factors related to the frequency of sexual activity of
      postmenopausal women METHODS: A cross-section study of 206 postmenopausal women
      between 45 and 60 years of age was made at a university health care service in
      the South of Brazil between June and October 2002. Evaluations were made of
      sexual activity according to the number of sexual intercourses in the previous
      month and the climacteric symptoms using the Kupperman index. Statistical
      analysis was performed with multiple linear regression analysis. RESULTS: Of
      those surveyed 176 (85%) women were sexually active. Although 60.6% reported a
      decrease in sexual activity after menopause, mostly attributing it to the
      husband's sexual impotence (41.7%). Approximately 25.7% stated they had no
      satisfaction with sexual intercourse. By means of multiple linear regression
      analysis the following aspects were associated to sexual activity: age (p<0.1),
      degree of sexual satisfaction (p=0.01), and climacteric symptomatology (p=0.02).
      As age increased the climacteric symptoms were more intense and sexual activity
      was less frequent with lower sexual satisfaction. The climacteric symptoms
      correlated with sexual activity were: hot flashes (p=0.05), irritability
      (p=0.04), melancholy/sadness (p=0.04), arthralgia/myalgia (p<0.01) and
      weakness/tiredness (p<0.01). CONCLUSION: Findings of this study were similar to
      those in literature. They agree with the hypothesis that sexuality of climacteric
      women is not only influenced by factors related to hypoestrogenism, but also by
      psychosocial and cultural aspects associated with aging itself. Nevertheless,
      longitudinal studies are necessary to provide more conclusive data. Special
      attention should be given to the sexual dysfunction of men.

PMID- 16967146
TI  - [Echocardiographic findings in children with "innocent" murmur].
AB  - OBJECTIVES: To access the frequency of abnormal echocardiographic findings in
      patients with diagnosis of innocent murmur. METHODS: A transversal study of 166
      consecutive patients was carried out with diagnosis of innocent murmur evaluated
      in the pediatric cardiology outpatient clinic of "Instituto de
      Cardiologia/Fundacao Universitaria de Cardiologia", a tertiary reference center,
      between December 3, 2001 and December 2, 2002. History, clinical examination and
      echocardiogram were performed in all patients. Post-test probabilities of disease
      with positive and negative clinical examination were estimated, considering the
      echocardiogram as gold standard. RESULTS: Of the 166 patients evaluated, 11
      showed some alteration in the echocardiogram: pulmonary stenosis (4), patent
      foramen ovale (2), atrial septal defect (1), bicuspid aortic valve (2), minimum
      aortic regurgitation (1) and ventricular septal defect (1). Negative post-test
      probability (probability of disease with diagnosis of innocent murmur) was of
      6.6%. CONCLUSION: In a referral outpatient clinic the proportion of minor lesions
      is high in patients with diagnosis of innocent murmur. These injuries may not be
      related to the heart murmur, as in the patent foramen ovale and bicuspid aortic
      valve. However, they raise the question of the indication of echocardiogram
      taking into account the low risk of detected lesions and, on the other hand, the
      resolutive character of a daycare reference center.

PMID- 16967147
TI  - [Pre-menstrual cyclic mastalgia].
AB  - OBJECTIVES: To compare therapeutic effects of placebo with intake of low doses of
      acetyl-salysilic acid (aspirin) and a compound of retinol, pyridoxine
      chlorhydrate and tocopherol acetate. METHODS: The study is a prospective,
      controlled, triple blinded, randomized trial. From 259 patients, 81 were selected
      in order to follow rigid criteria of inclusion. They were divided into three
      groups of 27 patients, taking aspirin, vitamins or placebo respectively. The
      number of patients in each group was considered satisfactory for statistical
      analysis. Pain was scored as Grade 1 (without pain), Grade II (moderate pain) and
      Grade III (severe pain). The Tukey test was applied for comparison of results
      (statistical significance 5%). RESULTS: Clinical parameters, age, weight, BMI,
      parity and lactation period were similar for each group. There was a decrease of
      pain intensity in all groups, that was even more pronounced for the placebo
      group. DISCUSSION: Emphasis was given to symptomatic treatment of cyclic
      premenstrual mastalgia with symptoms considered to be the expression of a
      physiological process that can be treated with simple drugs or placebo. Usual
      therapeutic approaches with several drugs are criticized, including results and
      contraindications. CONCLUSION: This study based upon acceptable trial methodology
      (randomized, triple blinded, placebo controlled, prospective) did not show
      significant differences in the treatment of cyclic mastalgia.

PMID- 16967148
TI  - [Simulation of D1 lymphadenectomy in patients submitted to D2 lymphadenectomy.
      Prospective study of 57 patients with gastric adenocarcinoma].
AB  - BACKGROUND: To simulate a D1 lymphadenectomy in 57 patients who had already been
      submitted to D2 lymphadenectomy, and analyze stage migration using the Japanese
      Gastric Cancer Association (JGCA) staging system. METHODS: All patients underwent
      a D2 lymphadenectomy between August 1997 and November 2001. At the end of
      surgery, the surgeon himself separated all lymph node stations. The parameters
      analyzed were: sex, age, lymph node invasion and number of dissected nodes. All
      patients were re-staged based on the new data, in order to evaluate the stage
      migration according to the JGCA staging system. RESULTS: The advanced tumors
      corresponded to 80.70% and the early ones to 19.30%. In 43.90% there were
      positive nodes at N1 and N2 levels. The mean number of dissected lymph nodes was
      28.63 in each patient. In IA, IB and II tumors, there were no changes in the
      stage after simulation of D1 lymphadenectomy. In ten IIIA tumors, three migrated
      to stage II and IB; in 21 tumors staged as IIIB, a migration was observed in 18;
      all stage IV tumors migrated to IIIB after the D1 simulation. CONCLUSION: a) D2
      lymphadenectomy is important for the correct staging of gastric cancer; b)
      simulation of D1 lymphadenectomy changed the stage of advanced tumors,
      particularly in stages IIIA, IIIB, and IV; c) D2 lymphadenectomy avoided residual
      lymph node disease in almost half of the patients operated.

PMID- 16967149
TI  - [Cox-2 and CD105 expression in breast cancer and disease-free survival].
AB  - OBJECTIVE: To verify the expression of CD105 in primary breast cancer, and the
      expression of cyclooxygenase-2 in primary breast cancer and in the respective
      axillary lymph nodes. METHODS: Seventy two women from 18 to 80 years of age, with
      a diagnosis of Ductal Infiltrative Breast Cancer, stage II, histological type non
      special, with their respective axillary lymph nodes were submitted to surgical
      treatment at the "Hospital Nossa Senhora da Conceicao" between 2001 and 2002.
      Immunohistochemical analyses of CD 105 in the primary breast cancer and of COX 2
      in the local axillary lymph node were compared for local recurrence. RESULTS: Of
      the 72 patients with primary tumors, 40 had positive axillary lymph nodes, while
      32 were negative. For each primary tumor, only one lymph node was analyzed. .
      Fifteen patients had local recurrence after 26 months (CI 95% 24-28). Presence of
      COX-2 in the primary tumors was verified in 52 cases, and presence of CD105 in 34
      cases. These independent prognostic factors were not correlated to local
      recurrence (P= 0.203 e P=0.145, respectively). The period free of local
      recurrence for patients with positive expression of COX-2 in axillary lymph nodes
      (with metastasis or not) was of 19 months, while patients with negative
      expression had a 28.3 months long period free of local recurrence. CONCLUSION:
      The positive expression of COX-2 in axillary lymph nodes (either positive or
      negative) seems to be an independent prognostic factor for local recurrence.

PMID- 16967150
TI  - The construction of nursing knowledge in the reflexive-comprehensive paradigm.

PMID- 16967151
TI  - Life experiences with Systemic Lupus Erythematosus as reported in outpatients'
      perspective: A clinical-qualitative study in Brazil.
AB  - This study aimed to know lupus outpatients' life experiences, in terms of the
      meanings they attributed to several phenomena associated to the process of
      becoming ill. Systemic Lupus Erythematosus is a chronic inflammatory disease,
      probably caused by a combination of inborn/hereditary predispositions and
      environmental factors, which leads to an abnormal stimulation of the immune
      system. Lupus life experience is associated to important psychosocial adaptation
      mechanisms of affected people. This work had a clinical-qualitative design and
      was performed in the dermatology service of a Brazilian General Hospital. The
      method included purposive sample, and a semistructured interview with open-ended
      questions was applied. After categorizing the interviewees' discourse, the
      discussion employed psychodynamic theories. The patients' reactions included the
      attempt to rebuild their relationships with their own strengths. Lupus patients'
      familiar and interpersonal conflicts seem to be associated with the idea that
      family and friends do not understand the nature of the disease.

PMID- 16967153
TI  - Analysis of proxemic communication with HIV/AIDS patients.
AB  - This descriptive and exploratory study analyzed the proxemic factors of the
      nursing team and HIV/AIDS patients in a hospital environment in Fortaleza - CE,
      between October and November 2004. Data were collected through non-participant
      observation. Forty-one interactions were analyzed, in which no gender influence
      was observed. The professional's position towards the patient was mainly
      standing; intimate distance occurred in 21.95% of interactions, which were mostly
      related to technical procedures; personal distance predominated in 63.41% of
      cases, which were related to technical care; social distance occurred in 14.64%
      of interactions, which were aimed at conservation; obstacles were present in 15
      interactions; local touch was the most frequent contact behavior; visual contact
      was present in 11 interactions, with a view to regulating the conversation flow;
      the tone of voice was found always adequate. Through proxemics, we can identify
      important factors in communication with HIV/AIDS patients.

PMID- 16967152
TI  - [The meaning of the new way of life of individuals with permanent intestinal
      ostomy].
AB  - The research aims to identify and analyze the main modifications that affect the
      way of life of an ostomate, and strategies developed to face the situation of
      having an ostomy. The method used was oral history of topic life. Ten semi
      structured interviews were conducted with permanent ostomates. For data analysis,
      the method used was thematic content analysis. Five themes emerged from the
      analysis of the interviews: the experience of signs and symptoms and the need for
      an ostomy; learning to live with an ostomy, the pouching system, and the search
      for alternatives to replace the usage of the pouching system; facing the changes
      caused by an ostomy in terms of feeding, clothing and sex life; the search for
      social reintegration, the challenge of facing death, and the search for future
      perspectives; the search for a social support network: religious and spiritual
      beliefs, family and the ostomates association.

PMID- 16967154
TI  - Ethical events in nursing: Daily activities of nurse managers and nursing ethics
      committee members.
AB  - This study aimed to understand the meaning of nurses' actions related to ethical
      occurrences involving nursing professionals. Data were collected through
      interviews with nurse managers and members of a Nursing Ethics Committee who
      experienced the phenomenon. Data were analyzed in the framework of social
      phenomenology. The nurses' experiences gave rise to the following categories of
      meaning, as these professionals seek: the humanization of nursing care;
      continuous improvement of the care process; professional credibility; patients'
      satisfaction; demystification of the fear of punishment; partnership in the
      educational process; respect for ethical secrecy and expectation related to the
      event being forwarded to the Nursing Ethics Committee. The social typification
      was described at the end. Nurses' actions in cases of ethical events attract the
      interest of nursing professionals, who want to ensure a risk or damage-free care
      and to promote the valuation of these professionals.

PMID- 16967155
TI  - [Motives which lead women not to return to receive the results of their pap smear
      test].
AB  - The Pap smear test is an efficient method of uterine cervical cancer prevention.
      For this prevention method to be effective, it is essential that the patient
      receives her results and satisfactorily concludes the treatment. This study aims
      to identify the motives which lead women not to return to receive the results of
      their Pap smear test. This is a descriptive research with a qualitative approach,
      carried out at a health centre in the city of Fortaleza, Ceara, Brazil. The study
      subjects are 21 women who underwent the Pap smear test and did not return to
      collect their results. The tool for data collection was a semi-structured
      telephone interview, held between September and November 2004. The results
      pointed to motives related to the patient, to the health professional delivering
      care and to the service offered.

PMID- 16967156
TI  - Medical reports recommending work restrictions at a teaching hospital in Brazil.
AB  - This non-experimental and cross-sectional descriptive study aimed to evaluate
      medical reports recommending work restrictions for workers at a teaching hospital
      in Brazil. A form was used for data collection, characterizing the medical
      reports and work restrictions, with its content previously validated. A total of
      176 medical reports was analyzed, containing 337 work restrictions, recommended
      from January 2001 to January 2004. The results demonstrated a high rate of work
      restrictions in the study hospital. The most restrictions frequent were ergonomic
      (78.6%), and the most often prescribed were: no weight lifting or carrying and no
      repetitive movements. There was an average of two restrictions per medical
      report, 79.5% of which were definitive and the mean restriction period was 13
      months.

PMID- 16967157
TI  - [The relation between work, health and living conditions: Negativity and
      positivity in nursing work at a teaching hospital].
AB  - This article results from a research carried out among nursing professionals at
      the Hospital das Clinicas da Universidade Federal de Uberlandia (MG), located in
      Uberlandia (MG), Brazil, and aimed to examine the relations between these
      professionals' work, health and living conditions. Data were collected through
      semistructured interviews and observations in the work environment. The results
      indicate the common occurrence of physical and mental health problems, mainly
      resulting from stress and exhaustion provoked by work conditions, which cause
      interferences in their living conditions. Paradoxically, the results show that
      these workers do not realize their health treatments systematically. The analysis
      of their work, in combination with the gender issue and the specific nature of
      nursing work, contributed to a better understanding of this professional group's
      work, living and health conditions.

PMID- 16967158
TI  - Cross-cultural adaptation of the Burns Specific Pain Anxiety Scale--BSPAS to be
      used with Brazilian burned patients.
AB  - This study aimed at translating and adapting the Burns Specific Pain Anxiety
      Scale--BSPAS and the Impact of Event Scale--IES into Portuguese; making available
      two simple, short and easily applicable instruments and describing the study
      participants according to their scores on the Visual Analogue Scale and the Trait
      State Anxiety Inventory. The cross-cultural adaptation process involved the
      following steps: translation of the scales; reaching a consensus in Portuguese;
      evaluation by an expert committee; back-translation; obtaining a consensus in
      Dutch; comparing the original versions with the consensus in Dutch; semantic
      analysis and pretest of the Portuguese versions. The results showed that both
      scales present high values of internal consistency between the scale items.
      Participants' average pain scores were higher after bathing and wound dressing.
      Participants' average anxiety scores were low or medium.

PMID- 16967159
TI  - [Stress among emergency unit nurses].
AB  - Stress is clearly present in nursing work. This article presents an exploratory
      study carried out among emergency unit nurses from hospital institutions, and
      aimed at determining these professionals' stress level. The sample consisted of
      73 emergency unit nurses who work for public and private institutions in the city
      of Sao Paulo. The data was collected through a structured questionnaire. The
      results indicated that emergency unit nurses present a medium stress level, and
      that participants considered E--Work Conditions to perform nursing activities,
      and F - Activities related to personnel administration, as the most stressful
      areas. For emergency unit nurses, in spite of the ready and effective action
      towards the instability of the patient's situation, conditions external to this
      situation are more stressful than the emergency. Hospitals need to analyze these
      requisites to allow for decreased stress among emergency nurses.

PMID- 16967160
TI  - [Identification of result evaluation criteria for nursing service in hospital
      accreditation programs].
AB  - The quality is already a part of daily reality in hospital organizations. Care is
      assessed through the organizational structures, work processes and obtained
      results. The goal was to identify the result evaluation criteria applied to the
      nursing service, used in accreditation programs, and to classify them in
      administrative, care and teaching/research activities. We carried out an
      exploratory, descriptive and quantitative study. Data were collected from 7
      companies accredited by the National Accrediting Organization. These sent us 8
      models, divided into groups A, B and C. Group A: models that use the manual;
      group B: models to which criteria were added; and group C: proper models. We
      identified 24 criteria: 13 administrative, 06 for care processes and 05 for
      teaching/research. Nursing services are evaluated with prominence to the
      administrative area, indicating that the other areas need to be reevaluated in
      terms of qualitative and quantitative aspects, in order to obtain more precise
      measurements.

PMID- 16967161
TI  - Hand hygiene: The impact of incentive strategies on adherence among healthcare
      workers from a newborn intensive care unit.
AB  - We carried out a before-after non-controlled intervention study to assess the
      impact of different handwashing strategies in health care workers at a neonatal
      ICU in Goiania - Goias, Brazil. All ethical aspects were considered. Data was
      collected by using a check list in order to register hand hygiene opportunities
      during six months. Three strategies were elaborated together with the hospital
      team. We observed 1358 handwashing opportunities. Incentive strategies caused a
      small impact on the increase of adherence to hand hygiene during and after the
      implementation period. However, we noticed that this increase mainly occurred
      after the procedures were realized. On the whole, adherence levels were similar
      before (62.2%) and after (61.6%) the procedures. The study showed that health
      care workers were more worried about individual risks.

PMID- 16967162
TI  - Perception of persons with severe or profound deafness about the communication
      process during health care.
AB  - This study describes a qualitative approach with the objective of characterizing
      the perceptions of people with severe or profound deafness about the
      communication process in the context of health care services. Study participants
      were 11 people with severe and/or profound deafness, who were interviewed using
      Brazilian sign language (LIBRAS). The interactions were videotaped and then
      transcribed. Care was taken to maintain the grammatical construction which was
      characteristic in the expression of each person. Three categories emerged from
      thematic analysis: Understanding, Need for Mediation, Feelings. Deaf persons do
      not achieve effective communication in health care, during which they experience
      negative feelings. Hence, the presence of a professional interpreter is needed.

PMID- 16967163
TI  - Evolution of nursing diagnoses for children with congenital heart disease.
AB  - We aimed to describe the evolution in nursing diagnoses for children with
      congenital heart disease. This longitudinal study was carried out from July to
      November of 2004. The sample consisted of 45 children interned in a public
      hospital in Fortaleza, Brazil, followed during fifteen days. In this period, we
      accomplished six diagnostic evaluations and found 21 nursing diagnoses. Six of
      these showed greater oscillations in their occurrence over time: Ineffective
      breathing pattern, Activity intolerance, Ineffective airway clearance,
      Hyperthermia, Sleep pattern disturbance, Risk for activity intolerance. Five
      parametric models were constructed in the time domain, with a view to predicting
      the occurrence of the nursing diagnoses. Knowledge about the temporal evolution
      in individuals' responses can guide nursing care towards the client's real needs.

PMID- 16967164
TI  - Socialization of children and adolescents with cystic fibrosis: Support for
      nursing care.
AB  - The aim of this paper is to identify the routine (school, work, free time
      activities and relationships with friends and family) of children and adolescents
      with Cystic Fibrosis (CF) through their experiences and identify situations that
      can affect these routines. The objects of analysis of this research are children
      and adolescents with CF who attend a teaching hospital in a city of the State of
      Sao Paulo--Brazil. It is a qualitative research, with data collection based on
      open interviews and patient charts. The data brought the following themes:
      misleading knowledge about the disease, concern with self-image, search for self
      care and hope of improvement in the future. The results evidence the repercussion
      of CF in those patients' socialization process, evidencing the importance of
      health professionals knowing about these demands and incorporating them into the
      care plan, with a view to effective interventions to promote infant-juvenile
      growth and development.

PMID- 16967165
TI  - [Intrafamily violence during adolescence in the city Puno--Peru].
AB  - This epidemiological case-control study aimed to describe the epidemiological
      profile of intrafamily violence against pregnant and non pregnant adolescents.
      The study was carried out at the outpatient clinic for central care to
      adolescents of the Regional Hospital Manuel Nunez Butron and at secondary schools
      in the city of Puno--Peru. The results were obtained by means of statistical
      analysis, verifying statistically significant differences for the occurrence of
      physical violence (p = 0.008) and sexual-rape violence (p = 0.01). The majority
      of the adolescents were victims of different types of aggression, executed either
      by members of the family (intrafamily) or by individuals outside the family
      (extrafamily). The most frequent causes associated to this aggression were
      disobedience, late arrival at home, having friends/boyfriends and doing domestic
      chores slowly.

PMID- 16967166
TI  - [Schizophrenia patients' daily life after the use of clozapine and group
      accompaniment: Family's view].
AB  - This study described the daily life of schizophrenia patients after the use of
      clozapine and group accompaniment from the perspective of family members. The
      research population consisted of 11 family members who most frequently
      accompanied 11 schizophrenia patients who participate in the group and use
      clozapine. With a view to data collection, interviews oriented by a script were
      held in April 2003, which were taped and fully transcribed afterwards. Results
      indicated an improvement in patients' symptoms, demonstrated by decreased social
      isolation, resumption of home/work activities and study as well as by
      participation in social events. These results point towards the need for a new
      view on patients who suffer from mental disorder and their family members, with a
      view to seeking therapeutic attitudes that act in the production of life with a
      view to a new existential meaning, in the different forms of social contact and
      sociability.

PMID- 16967167
TI  - [Cost analysis of reprocessing disposable forceps used in video-assisted
      surgery].
AB  - This study aimed to analyze the reprocessing costs of disposable forceps used in
      video-assisted surgery. The frequent reuse of these instruments is justified by
      their high cost. However, few studies have been carried out on this topic. The
      multiple case study method was applied in three hospitals in the State of Sao
      Paulo, using the observation and document analysis techniques. In case number
      one, the processing cost was R dollars 9.37, R dollars 6.59 for case number two
      and R dollars 3.31 for case number three. The low cost observed should be
      analyzed with caution, since it was observed that quality-control plays a role in
      the final cost. When the quality-control measures are adopted, the reprocessing
      costs jumped to R dollars 185.19 for case number one, R dollars 595.82 for case
      number two and to R dollars 363.10 for case number three.

PMID- 16967168
TI  - Professional socialization: students becoming nurses.
AB  - Usually colleges are evaluated by the quality of the knowledge and technical
      training offered to the students. Little attention is given to the acquisition of
      the values, behaviors and attitudes necessary to assume their professional role.
      This exploratory study aims to increase understanding of the professional
      socialization process that occurs at nursing schools and the results obtained
      through the socialization of professional values and standards. The educational
      experience of nursing students involves more than a body of scientific knowledge
      and the acquisition of abilities to provide care to patients. Questionnaires were
      filled out by 278 students of two public Nursing Schools in Sao Paulo state, 164
      in school A and 114 in school B. The results indicated that some professional
      values, norms and behaviors are influenced by College years, studying at a
      College of Nursing during four years leads to a difference in values, norms and
      professional behavior.

PMID- 16967169
TI  - [Analysis of publications on Nursing Interventions Classification (NIC) from 1980
      to 2004].
AB  - This study aimed at reviewing the knowledge produced about the Nursing
      Interventions Classification (NIC) available in the scientific literature from
      January 1980 to January 2004. NIC is a taxonomy with activities performed by
      nurses. Authors searched Lilacs and Medline databases, materials at the Center
      for Nursing Classification-University of Iowa College of Nursing and a doctoral
      dissertation obtained from a private library. The works found referred to the
      application of NIC to practice, the languages used in information systems, the
      use of NIC in these systems and the presentation, construction, development and
      validation of a taxonomy, among others. Authors concluded that there are several
      possibilities related to the production of knowledge on NIC in Brazil and that it
      is necessary to encourage studies on this taxonomy, raising questions and
      generating new knowledge to contribute to the improvement of Brazilian Nursing.

PMID- 16967170
TI  - [Brazilian research in oncology nursing: An integrative review].
AB  - We carried out an integrative literature review to characterize research produced
      by Brazilian oncology nursing. The bibliographic survey covered national nursing
      publications, from 1980 to 2004, from which we identified 84 articles, which
      composed the study sample. The results indicate the lack of clarifications to
      demonstrate study rigor in the analyzed articles. We suggest identifying research
      priorities, refining the strategies to synthesize research results, conducting
      studies rigorously, respecting the steps of the scientific method and taking
      greater care in the elaboration of reports submitted for publication.

PMID- 16967171
TI  - [Low back pain during gestation].
AB  - This research qualitatively analyzed the contents of national and international
      scientific publications, indexed in the period from 1999 to 2005, about low back
      pain in gestation. Around 50 % of pregnant women complain about low back pain.
      The physiologic modifications that occur happen in pregnancy alter the posture of
      pregnant women and the largest incidence of low back pain usually happens in the
      last three months. Specific causes remain unknown. However, treatment involves
      analgesics, antiphlogistics, exercises and physiotherapy. Low back pain during
      gestation is a symptom that causes great discomfort and, depending on the level
      of pain, it generates motor disability and impairs daily activities, besides
      causing problems to take care of the baby after birth. Some discomfort of low
      back pain can continue for a period of up to three years after childbirth. We see
      a great need for further research in this subject area, in order to provide a
      better quality of life for pregnant women.

PMID- 16967172
TI  - Violence against children and adolescents: A challenge in the daily work of the
      nursing team.
AB  - This article aims to reflect on various forms of violence against children and
      adolescents practiced in the family context, and the importance of professional
      nursing care in view of this phenomenon. We discuss possibilities of care and
      violence prevention as well as the problems violence causes to society. Violence
      is a social and historical problem, constructed in society, and needs to be
      adequately addressed in academic nursing education.

PMID- 16967173
TI  - [For a better dissemination of Portuguese pulmonology].

PMID- 16967174
TI  - [Six-minute walk work is not correlated to the degree of airflow obstruction in
      patients with Chronic Obstructive Pulmonary Disease (COPD)].
AB  - INTRODUCTION: The six-minute walking test distance, despite being considered the
      main parameter, does not consider body weight which is known to influence
      exercise capacity. A body of evidence shows the degree of airflow obstruction
      does not correlate to walking distance and the body weight affects the
      work/energy required to perform the walk. OBJECTIVE: To verify if the degree of
      airflow obstruction correlates to six-minute walk work obtained by weight-walking
      distance product. PATIENT AND METHODS: A total of 60 patients with chronic
      obstructive pulmonary disease were evaluated. The physiological and functional
      variables were correlated to distance and body weight walking distance product
      (WxW). RESULTS: There were no correlations between six- minute walk work and the
      degree of airflow obstruction. A positive and significant correlation were
      observed between the distance and Carbon Monoxide Diffusing Capacity (DLCO)
      (r=0.6; p<0.01) and between the distance and final SatO 2 (r= 0.3 ; p <0.05).
      Correlation between distance and Borg scale was negative and significant (r= 
      0.3; p<0.05). The six-minute walk work was positive and significantly correlated
      to DLCO (r= 0.7; p<0.01) and negative but significantly correlated to Borg scale
      in the initial (r= - 0.3; p<0.01) and final of the test (r= -0.4; p<0.05).
      CONCLUSION: Based on this data, there was no correlation between the degree of
      airflow obstruction and six-minute walk work test. The DLCO was the only
      respiratory functional parameter significantly correlated to the distance and to
      the six- minute walk work.

PMID- 16967175
TI  - [Lung adenocarcinoma: application of the WHO 1999/2004 classification to the
      caseload of the Pathologic Anatomy Service at the Hospital of the Coimbra
      University].
AB  - A study of 701 primary adenocarcinomas of the lung was made at the Department of
      Pathology of the Hospital da Universidade de Coimbra for a period of fifteen
      years, between 1990 and 2004. In the same period 382 metastases were diagnosed,
      mainly from colon (119) and breast (66). The incidence of primary adenocarcinomas
      varied from 16 cases in 1990 to 49 cases in men and from 12 to 37 cases in women
      in that period. From 2001 onwards, the incidence was almost coincident in both
      genders. In the last four years, since 2001, patients were in the seventies at
      the time of diagnosis and a considerable number of cases were diagnosed after 80
      years of age. The criteria defined by the WHO classification of Tumours of the
      Lung, Pleura, Thymus and Heart 2004 were applied to the primary adenocarcinomas
      of the lung and as was expected, bronchioloalveolar carcinomas had its incidence
      in women while acinar adenocarcinomas were diagnosed mainly in men. These
      conclusions were obtained via surgical specimens and when surgical biopsies were
      representative and those were mainly in stage IIB and IIIA. A number of 109 cases
      had the final diagnosis of adenocarcinoma of the lung based on morphology and
      immunohistochemistry criteria.

PMID- 16967176
TI  - [Glomic tumor: presentation of an infrequent case].
AB  - Glomic tumours are perivascular tumours whose cells resemble modified smooth
      muscular cells of the glomic body. They are more frequent in the subungueal
      region and rare in the lung. The authors present a case of a 62 year old women
      with left thoracic pain and great enforces dyspnoea. She presented a solitary
      nodule in the external basal segment of the LLL, 1.9 cm diameter, circumscribed,
      firm and with nodular whitish rose cut surface. Glomic tumours are generally
      benign. They may origin in ectopic glomic cells or be differentiated from non
      glomic cells. They should be classified as glomic tumor, glomangioma and
      glomangiomioma according to the relative abundance of glomic cells and of the
      vascular and muscular components. Pulmonary metastasis of malignant glomic
      tumours have been described. In these cases an extra pulmonary primary origin
      must be excluded. The differential diagnosis of glomic tumours of the lung
      includes the carcinoid, hemangioperycitoma, smooth muscle tumours (epithelioid
      leyomioma) and the paraganglioma.

PMID- 16967177
TI  - [Mediastinal angiofolicular lymphoid hyperplasia--Castleman's disease--case
      report].
AB  - Angiofolicular lymphoid hyperplasia was first described by Castleman as a lymph
      node hyperplasia characterized by abnormal follicles with small germinal centres
      and high capillary proliferation. The authors present a case of a 37 year old man
      with thoracalgy and a mediastinal mass of 4 cm diameter, fleshy and red with a
      white central area. The diagnosis of plasma cell type of angiofolicular lymphoid
      hyperplasia in an mediastinal lymph node was made. He also had involvement of two
      "diaphragmatic" lymph nodes. Angiofolicular lymphoid hyperplasia--Castleman's
      disease--is a rare lymphoproliferative disease that involves the mediastine or
      the pulmonary hilus when of solitary form but it can also have other
      localizations (multicentric or systemic form). Two histological variants are
      described, the hyaline vascular type and the plasma cell type. IL-6 seems to be
      in the plasma cell type, due to plasma cells proliferation. Castleman's Disease
      must be considered in the differential diagnosis of mediastinal masses, namely
      lymphomas.

PMID- 16967178
TI  - [Mechanical ventilation and medical futility or dysthanasia, the dialectic of
      high technology in intensive medicine].
AB  - Dysthanasia or any of its synonyms is a consequence of excessive technical
      science, without any reasonable chance of achieving a therapeutic benefit for the
      patient. Medical futility is a distressing ethical dilemma of intensive care
      medicine. Its recognition has led to a precept support in various institutions
      and organizations. Not withdrawing or withholding mechanical ventilation in
      certain circumstances can be considered as a paradigmatic model of medical
      futility. The understanding of this posture implies a philosophical approach and
      reflexion of medical practice.

PMID- 16967179
TI  - [About a case of common variable immunodeficiency--revision of
      hypogammaglobulinemias].
AB  - Common variable immunodeficiency is a primary immune deficiency characterized by
      heterogeneous immunologic disorders of unknown etiology. Its clinical
      manifestations include recurrent infections, autoimmune diseases, lymphoid
      hyperplasia, granulomatous diseases and malignancy. It can appear in patients
      with immunoglobulin A deficiency. The authors report the clinical case of a
      patient with common variable immunodeficiency and history of respiratory
      infections from the age of 9 months old, associated with the appearing of
      bronchiectasis.

PMID- 16967180
TI  - [Unusual diagnosis of tracheal obstruction].
AB  - Male, 54 years old, with smoking habits. The patient complaints were cough, with
      bleeding secretions in the previous two months. Because of the persistence of the
      symptoms, a bronchoscopy was proposed. This exam showed multiple lesions in the
      trachea, nearly 2 cm above the vocal cords that compromised the airway and did
      not allow the progression of the bronchoscope. For this reason, it was decided to
      introduce a tracheal prosthesis. Because of instability, and the suspicion of
      malignancy we started thoracic irradiation. The histological specimen was
      compatible with anaplastic Lymphoma, CD 30+. Because of respiratory distress,
      with stridor, the prosthesis was removed. The trachea was permeable after this.
      The patient was discharged and oriented to Clinical Haematology. He is clinically
      stable and under monitoring, having now completed a chemotherapy treatment with
      CHOP (Ciclophosphamide, Adriamycin or Hydroxydorubicin, Vincristine or Oncovin
      and Prednisone). The primary mediastinal Large Cells Lymphoma represents 11.5% of
      the Large Cells Lymphomas (2% of the non-Hodgkin's Lymphomas). This neoplasm is
      in many studies considered incurable, but there are some positive results with
      the combination of radiotherapy and chemotherapy. If there is any airway
      compromise, the tracheal prosthesis may be one option for the resolution of the
      respiratory insufficiency.

PMID- 16967181
TI  - [Traumatic diaphragmatic hernias: retrospective analysis].
AB  - AIMS: This study classifies cases of traumatic diaphragmatic hernias (TDH) in
      patients admitted to the Intensive Care Unit (ICU) of the Coimbra University
      Hospitals (HUC) from 1990 to 2004. METHODS: Retrospective analysis of 34 cases of
      TDH, studying anatomical location, place and time of diagnosis, complementary
      tests aiding diagnosis, herniated organs, associated traumatism, morbidity and
      mortality. RESULTS: Twenty-eight male and six female patients with an average age
      of 40.5 years +/- 20.5, average SAPS score 38.8. Average length of stay was 19.1
      +/- 13.6 days, all suffered from closed traumatism and were put on artificial
      ventilation. The left-side diaphragm was more frequently affected (94.1%) then
      the right. Diagnosis in 19 cases was made up in the first six hours following the
      diagnosis of traumatism, in four cases within 12 hours and in the remaining cases
      between 48 hours and 16 years after traumatism. In 13 patients the diagnosis was
      established intra-operatively. The stomach was typically one of the herniated
      organs. The most frequently associated lesions at the thoracic level were
      pulmonary contusion, haemothorax and pneumothorax, and at the abdominal level,
      haemoperitoneum and splenic lesion. The rates for complications and mortality
      were 55.8% and 11.7% respectively. CONCLUSIONS: TDH mainly occurs on the left
      side through closed thoraco-abdominal trauma following road traffic accidents.
      This group of patients, on average younger than others admitted to ICU, presents
      a longer average hospitalisation period, but has lower rates of mortality and
      lower SAPS severity scores. The most commonly herniated organ was the stomach and
      the most frequently encountered lesions were cranial-encephalic, splenic and
      pleural traumatisms. Pre-operative diagnosis of diaphragmatic injuries is
      difficult and a high index of clinical suspicion is needed after thoraco
      abdominal trauma. This diagnosis should always be considered a possibility in
      cases of closed thoraco-abdominal traumas.

PMID- 16967182
TI  - Heavy metal-induced differential gene expression of metallothionein in Javanese
      medaka, Oryzias javanicus.
AB  - A metallothionein (MT) gene was isolated for the first time from Javanese medaka,
      Oryzias javanicus, which shows high adaptability from freshwater to seawater. The
      full-length cDNA of MT from O. javanicus (OjaMT) comprises 349 bp, excluding the
      poly(A)+ stretch, and codes for a total of 60 amino acids. The positions of
      cysteine residues are highly conserved. The pattern of OjaMT expression induced
      by six heavy metals was analyzed via real-time quantitative polymerase chain
      reaction (PCR). The level of hepatic OjaMT mRNA was increased in a dose-dependent
      manner by Ag, Cd, Cu, and Zn after 24 h of exposure. However, after Cr and Ni
      exposure, a significant decrease in OjaMT levels was observed. Cadmium-induced
      OjaMT expression was detectable in fishes as young as 3 months. After Cd
      exposure, OjaMT induction was prominent in intestine and liver and moderate in
      muscle and gill. OjaMT mRNA levels could represent a good biomarker for
      monitoring heavy metals in seawater.

PMID- 16967183
TI  - A male reproduction-related Kazal-type peptidase inhibitor gene in the prawn,
      Macrobrachium rosenbergii: molecular characterization and expression patterns.
AB  - Peptidase inhibitors in the male reproductive tract are well known in mammals, in
      which they play roles in protecting the tract epithelium against proteolytic
      damage or in regulating the fertilization process. By screening the subtracted
      cDNA clones enriched for male reproductive tract-specific transcripts, one clone
      encoding a putative protein that showed significant similarity to Kazal-type
      peptidase inhibitor (KPI) was obtained. This is the first report of an
      invertebrate in which a male reproductive tract-specific KPI gene has been
      identified and characterized. The gene contains a 405-bp open reading frame
      (ORF), a 72 bp 5' untranslated region (UTR), and a 259 bp 3' UTR. The
      conceptually translated protein consisted of a 21-amino-acid signal peptide and a
      113-amino-acid mature polypeptide with two Kazal-type domains (named after the
      discoverer). Significant levels of the mRNA were observed only in the male
      reproductive tract, while mRNA expression was not detected in any other tissues
      tested. The transcription of the gene remained constant during maturation,
      although not in the postlarval stage. In situ hybridization demonstrated the
      presence of the mRNA in the secretory epithelial cells of vas deferens and
      terminal ampullae.

PMID- 16967185
TI  - Comprehensive profiling of N-acylhomoserine lactones produced by Yersinia
      pseudotuberculosis using liquid chromatography coupled to hybrid quadrupole
      linear ion trap mass spectrometry.
AB  - A method for the comprehensive profiling of the N-acylhomoserine lactone (AHL)
      family of bacterial quorum-sensing molecules is presented using liquid
      chromatography (LC) coupled to hybrid quadrupole-linear ion trap (QqQLIT) mass
      spectrometry. Information-dependent acquisition (IDA), using triggered
      combinations of triple-quadrupole and linear ion trap modes in the same LC-MS/MS
      run, was used to simultaneously screen, quantify and identify multiple AHLs in a
      single sample. This MS method uses common AHL fragment ions attributed to the
      homoserine moiety and the 3-oxo-, 3-hydroxy- or unsubstituted acyl side chains,
      to identify unknown AHLs in cell-free culture supernatants in an unbiased manner.
      This LC-MS technique was applied to determine the relative molar ratios of AHLs
      produced by Yersinia pseudotuberculosis and the consequences of inactivating by
      mutation either or both of the AHL synthase genes (ypsI and ytbI) on AHL profile
      and concentration. The Y. pseudotuberculosis wild type but not the ypsI ytbI
      double mutant produced at least 24 different AHLs with acyl chains ranging from
      C4 to C15 with or without 3-oxo or 3-hydroxy substituents. YtbI, in contrast to
      YpsI, could direct the synthesis of all of the AHLs identified. The most abundant
      and hence most biologically relevant Y. pseudotuberculosis AHLs were found to be
      the 3-oxo-substituted C6, C7 and C8 AHLs and the unsubstituted C6 and C8
      compounds. The LC-QqQLIT methodology is broadly applicable to quorum-sensing
      signal molecule analysis and can provide comprehensive AHL profiles and
      concentrations from a single sample and simultaneously collect confirmatory
      spectra for each AHL identified.

PMID- 16967186
TI  - Electrocatalytic reduction of hydrogen peroxide on modified graphite electrodes:
      application to the development of glucose biosensors.
AB  - The electrocatalytic activities of a series of compact graphites modified with
      microquantities of platinum metals (Pd or Pt+Pd) towards the electrochemical
      reduction of hydrogen peroxide were characterised. Operational parameters such as
      the optimal working potential, the influence of temperature and the resulting
      electrode characteristics were examined. The benefits of using graphite modified
      with Pt+Pd (mixture ratio 30%:70%) as the basic transducer in a glucose biosensor
      with improved sensitivity were demonstrated. It was proven that, under the
      working conditions chosen, the selected electrode (whether bare or covered with
      an enzyme layer) did not respond to any glutathione, uric acid or ascorbic acid
      (which all normally occur in biological fluids) present.

PMID- 16967187
TI  - Expression of discoidin domain receptor 2 (DDR2) extracellular domain in pichia
      pastoris and functional analysis in synovial fibroblasts and NIT3T3 cells.
AB  - Discoidin domain receptor 2 (DDR2) is a kind of protein tyrosine kinases
      associated with cell proliferation and tumor metastasis, and collagen, identified
      as a ligand for DDR2, up-regulates matrix metallloproteinase 1 (MMP-1) and MMP-2
      expression in cellular matrix. To investigate the roles of DDR2 in destruction of
      cartilage in rheumatoid arthritis (RA) and tumor metastasis, we tried to express
      extracellular domain of DDR2 fused with a His tag to increase protein solubility
      and facilitate purification (without signal peptide and transmembrane domain,
      designated DR) in Pichia pastoris, purify the expressed protein, and characterize
      its function, for purpose of future application as a specific DDR2 antagonist.
      Two clones of relative high expression of His-DR were obtained. After
      purification by a Ni-NTA (nitric-tri-acetic acid) chromatographic column, soluble
      fused His-DR over 90% purity were obtained. Competitive binding inhibition assay
      demonstrated that expressed His-DR could block the binding of DDR2 and natural
      DDR2 receptors on NIT3T3 and synovial cell surfaces. Results of RT-PCR, Western
      blotting, and gelatinase zymography showed that His-DR was capable of inhibiting
      MMP-1 and MMP-2 secretion from NIT3T3 cells and RA synoviocytes stimulated by
      collagen II. For MMP-1, the inhibitory effect was displayed at the levels of mRNA
      and protein, whereas for MMP-2 it was demonstrated at the level of protein
      physiological activity. All these findings suggested that the fused expressed His
      DR inhibited the activity of natural DDR2, and relevant MMP-1 and MMP-2
      expression in synoviocytes and NIH3T3 cells provoked by collagen II.

PMID- 16967188
TI  - Tethered cord syndrome in a 24-year-old woman presenting with urinary retention.
AB  - We discuss a case of newly diagnosed tethered cord syndrome (TCS) in a 24-year
      old woman who presented with dysuria, hematuria, and urinary retention. Physical
      exam revealed hyperreflexic lower extremity deep tendon reflexes. MRI showed
      filum terminale terminating in a lipoma, consistent with TCS. We discuss the role
      of MRI in the workup of adults with bladder dysfunction.

PMID- 16967189
TI  - What's a 'cure'? Patient-centred outcomes of treatments for stress urinary
      incontinence.

PMID- 16967190
TI  - Serum 25-hydroxyvitamin D, parathyroid hormone, and bone mineral density in men:
      the Rancho Bernardo study.
AB  - INTRODUCTION: This study examined the distribution and determinants of serum 25
      hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) and their associations
      with bone mineral density (BMD) at the hip and spine in 414 older men (mean age
      74 years) living in southern California. METHODS: At a clinic visit (1997-2000),
      demographic and lifestyle information, fracture history, and medication use were
      recorded; venous blood for serum 25OHD and PTH was obtained; and BMD was measured
      at the hip and spine. RESULTS: Only one man had vitamin D deficiency (25OHD <20
      nmol/l), but 15.5% of the men had high parathyroid levels (PTH >or=65 pg/ml). The
      mean 25OHD and PTH levels were 109.0 nmol/l and 50.3 pg/ml, respectively.
      Overall, 21.5% used calcium and 9.7% used vitamin D supplements. Serum 25OHD
      decreased with age and was lowest in the winter; levels were higher in supplement
      users (vitamin D and/or calcium; p<0.01). Serum PTH did not vary by age or
      season, and it was lower in supplement users (p<0.01). After excluding 12 men who
      were outliers for serum 25OHD and PTH, there was no significant correlation
      between serum 25OHD and PTH (r=-0.05, p=0.3). In multiple adjusted models, serum
      25OHD was positively associated with BMD at the hip (p=0.01) and spine (p=0.001).
      Serum PTH was moderately and inversely associated with BMD at the hip (p=0.04)
      but not at the spine (p=0.77). CONCLUSION: We conclude that serum 25OHD is
      associated with bone health in older, community-dwelling men.

PMID- 16967191
TI  - Long-term survival in a patient with AL amyloidosis after cardiac transplantation
      followed by autologous stem cell transplantation.

PMID- 16967192
TI  - Factors influencing the intake and plasma levels of calcium, phosphorus and
      magnesium in southern Spain.
AB  - OBJECTIVE: The aim of the study was to assess factors influencing the intake and
      plasma levels of calcium (Ca), phosphorus (P) and magnesium (Mg) in an adult
      population from southern Spain, in order to identify patterns of intake and
      groups at risk for deficiency. METHODS: A cross-sectional survey was carried out
      in Andalusia, a western Mediterranean region in southern Spain. Nutrient intakes
      were studied in a random sample of 3,421 subjects (1,747 men, 1,674 women)
      between 25 and 60 years of age. Blood samples were obtained for biochemical
      assays in a random subsample of 354 subjects (170 men, 184 women). Food
      consumption was assessed by a 48-h recall. Concentrations of Ca, P and Mg were
      measured in plasma. Information about level of education, smoking habit, alcohol
      consumption and physical exercise was collected with a structured questionnaire.
      RESULTS: Intakes were below two-thirds of the RDA in 39.52% of the sample for Ca,
      and in 32.31% for Mg. Gender, age, educational level, obesity, smoking, alcohol
      use and physical activity were associated with differences in nutrient intakes.
      Plasma concentrations were below the reference value in 14.81% of the sample for
      Ca, and in 8.82% for Mg. Obese persons [body mass index (BMI) >/= 30 kg/m(2)]
      consumed less Ca, P and Mg, and had lower plasma Ca concentrations (P < 0.05)
      than non-obese persons. BMI showed an inverse correlation with plasma
      concentrations of Ca (r = -0.21, P < 0.05). CONCLUSION: Our results provide an
      estimate of the intake of Ca, P and Mg in the adult population of southern Spain.
      Of the factors that affected the intake of these nutrients, logistic regression
      analysis showed that only female gender and older age were associated with the
      risk of low plasma Ca concentrations.

PMID- 16967194
TI  - Measurement of 15N relaxation in deuterated amide groups in proteins using direct
      nitrogen detection.
AB  - 15N chemical shielding tensors contain useful structural information, and their
      knowledge is essential for accurate analysis of protein backbone dynamics. The
      anisotropic component (CSA) of 15N chemical shielding can be obtained from 15N
      relaxation measurements in solution. However, the predominant contribution to
      nitrogen relaxation from 15N-(1)H dipolar coupling in amide groups limits the
      sensitivity of these measurements to the actual CSA values. Here we present
      nitrogen-detected NMR experiments for measuring 15N relaxation in deuterated
      amide groups in proteins, where the dipolar contribution to 15N relaxation is
      significantly reduced by the deuteration. Under these conditions nitrogen spin
      relaxation becomes a sensitive probe for variations in 15N chemical shielding
      tensors. Using the nitrogen direct-detection experiments we measured the rates of
      longitudinal and transverse 15N relaxation for backbone amides in protein G in
      D(2)O at 11.7 T. The measured relaxation rates are validated by comparing the
      overall rotational diffusion tensor obtained from these data with that from the
      conventional 15N relaxation measurements in H(2)O. This analysis revealed a 17-24
      degree angle between the NH-bond and the unique axis of the 15N chemical
      shielding tensor.

PMID- 16967193
TI  - A simple and reliable approach to docking protein-protein complexes from very
      sparse NOE-derived intermolecular distance restraints.
AB  - A simple and reliable approach for docking protein-protein complexes from very
      sparse NOE-derived intermolecular distance restraints (as few as three from a
      single point) in combination with a novel representation for an attractive
      potential between mapped interaction surfaces is described. Unambiguous
      assignments of very sparse intermolecular NOEs are obtained using a reverse
      labeling strategy in which one the components is fully deuterated with the
      exception of selective protonation of the delta-methyl groups of isoleucine,
      while the other component is uniformly (13)C-labeled. This labeling strategy can
      be readily extended to selective protonation of Ala, Leu, Val or Met. The
      attractive potential is described by a 'reduced' radius of gyration potential
      applied specifically to a subset of interfacial residues (those with an
      accessible surface area > or = 50% in the free proteins) that have been
      delineated by chemical shift perturbation. Docking is achieved by rigid body
      minimization on the basis of a target function comprising the sparse NOE distance
      restraints, a van der Waals repulsion potential and the 'reduced' radius of
      gyration potential. The method is demonstrated for two protein-protein complexes
      (EIN-HPr and IIA(Glc)-HPr) from the bacterial phosphotransferase system. In both
      cases, starting from 100 different random orientations of the X-ray structures of
      the free proteins, 100% convergence is achieved to a single cluster (with near
      identical atomic positions) with an overall backbone accuracy of approximately 2
      A. The approach described is not limited to NMR, since interfaces can also be
      mapped by alanine scanning mutagenesis, and sparse intermolecular distance
      restraints can be derived from double cycle mutagenesis, cross-linking combined
      with mass spectrometry, or fluorescence energy transfer.

PMID- 16967195
TI  - Toward automated biochemotype annotation for large compound libraries.
AB  - Combinatorial chemistry allows scientists to probe large synthetically accessible
      chemical space. However, identifying the sub-space which is selectively
      associated with an interested biological target, is crucial to drug discovery and
      life sciences. This paper describes a process to automatically annotate
      biochemotypes of compounds in a library and thus to identify bioactivity related
      chemotypes (biochemotypes) from a large library of compounds. The process
      consists of two steps: (1) predicting all possible bioactivities for each
      compound in a library, and (2) deriving possible biochemotypes based on
      predictions. The Prediction of Activity Spectra for Substances program (PASS) was
      used in the first step. In second step, structural similarity and scaffold
      hopping technologies are employed. These technologies are used to derive
      biochemotypes from bioactivity predictions and the corresponding annotated
      biochemotypes from MDL Drug Data Report (MDDR) database. About a one million
      (982,889) commercially available compound library (CACL) has been tested using
      this process. This paper demonstrates the feasibility of automatically annotating
      biochemotypes for large libraries of compounds. Nevertheless, some issues need to
      be considered in order to improve the process. First, the prediction accuracy of
      PASS program has no significant correlation with the number of compounds in a
      training set. Larger training sets do not necessarily increase the maximal error
      of prediction (MEP), nor do they increase the hit structural diversity. Smaller
      training sets do not necessarily decrease MEP, nor do they decrease the hit
      structural diversity. Second, the success of systematic bioactivity prediction
      relies on modeling, training data, and the definition of bioactivities
      (biochemotype ontology). Unfortunately, the biochemotype ontology was not well
      developed in the PASS program. Consequently, "ill-defined" bioactivities can
      reduce the quality of predictions. This paper suggests the ways in which the
      systematic bioactivities prediction program should be improved.

PMID- 16967196
TI  - An easy access to 2-Amino-5,6-dihydro-3H-pyrimidin-4-one building blocks: the
      reaction under conventional and microwave conditions.
AB  - A new one-stage fast multicomponent synthesis of title compounds leads to
      products in 21-55% isolated yields under both conventional and microwave
      conditions. The primary amino group in the building blocks can be easily acylated
      by various usual electophilic agents that can be utilized in the synthesis of
      diverse heterocylic compounds libraries.

PMID- 16967197
TI  - Synthesis of functionalized 5-imino-2,5-dihydro-furans through the reaction of
      isocyanides with activated acetylenes in the presence of ethyl bromopyruvate.
AB  - The reaction between alkyl(aryl) isocyanides and dibenzoylacetylene in the
      presence of ethyl bromopyruvate leads to ethyl 3,4-dibenzoyl-2-bromomethyl-5
      alkyl(aryl)imino-2,5-dihydro-furan-2-carboxylates in high yields. Dialkyl
      acetylenedicarboxylates react with tert-butyl isocyanide and ethyl bromopyruvate
      to produce 3,4-dialkyl 2-ethyl 2-bromomethyl-5-tert-butylimino-2,5-dihydro-furan
      2,3,4-tricarboxylates.

PMID- 16967198
TI  - An unusual case of foreign body knee that spontaneously migrated inside and out
      of the joint: arthroscopic removal.
AB  - Cause of acute knee pain and locking episodes in a young sports person can be due
      to foreign bodies which penetrated unnoticed into the joint cavity. Here we
      report an unusual injury of this kind where a glass foreign body remained in the
      subcutaneous tissue for many years and then migrated late into the knee joint
      cavity. Complaints occurred for the first time in adult age. Arthroscopy revealed
      a circular defect in the posterior capsule beyond which a 1.6 cm glass foreign
      body was lying in an extra capsular location. The late and episodic migration of
      the glass piece into the joint from its extracapsular location produced symptoms
      of acute pain and locking. There is no reported case of such spontaneous and
      episodic migration of a glass foreign body inside and out of the knee joint
      resulting in acute episodes of pain and locking during sporting activity
      mimicking a torn meniscus or a chondral lesion. This report highlights the
      importance of accurate history taking, thorough physical examination, besides
      describing this unusual extra capsular location of the glass foreign body during
      arthroscopic surgery.

PMID- 16967199
TI  - Clinical disability in posterior cruciate ligament deficient patients does not
      relate to knee laxity, but relates to dynamic knee function during stair
      descending.
AB  - We investigated the factors which influence clinical subjective symptoms during
      activities in PCL deficient patients by evaluating knee laxity, muscle strength
      and knee mechanics during level walking, stair ascent and descent. Twenty-two
      subjects with isolated PCL deficient knees and 20 healthy volunteers were
      involved. The PCL deficient patients were divided into two subgroups based on
      previous history of experiencing giving-way during stair descent; a giving-way
      group (10 subjects) and a non giving-way group (12 subjects). Giving-way during
      activities of daily living is a key symptom in isolated PCL deficient patients.
      No statistically significant differences in the knee laxity, muscle strength and
      knee mechanics during level walking and were observed between the giving-way
      group and the non giving-way group. However, we found significant differences in
      the knee mechanics during stair ascent and descent between the two groups, and
      these differences were more remarkable during stair descent. Peak values of knee
      flexion angle, external knee flexion moment and posterior knee force during early
      stance phase were significantly lower in the giving-way group than in the non
      giving-way group. This study indicated that the symptom of giving-way during
      stair descent was related to knee mechanics during stair descent, unlike other
      quantitative evaluations such as KT-2000 or Biodex.

PMID- 16967200
TI  - Arthroscopic reduction and internal fixation of an avulsion fracture of the
      posterior horn of the lateral meniscus.
AB  - We report a very rare case of an avulsion fracture of the posterior horn of the
      lateral meniscus associated with ACL tear, which was successfully treated by
      arthroscopic reduction and pullout fixation of the fragment along with ACL
      reconstruction.

PMID- 16967201
TI  - Mid-term clinical results of medial meniscus repair with the meniscus arrow in
      the unstable knee.
AB  - The medial meniscus is a secondary stabilizer to anterior tibial translation and
      provides significant stability, especially in an ACL-deficient knee. The purpose
      of this study is to evaluate the clinical outcome of medial meniscus repair in
      the unstable knee. Between 1997 and 2002, 11 patients, with a mean age of 25.8
      years (range 15-39 years), underwent all-inside medial meniscus repair, using the
      Meniscus Arrow, for unstable medial meniscus tear in ACL-deficient knees. For
      various reasons none of these patients underwent ACL reconstruction. The average
      follow-up was 73 months (range 52-91 months). There were three failures (27.3%)
      defined as the need for reoperation and partial meniscectomy. The mean Tegner
      activity score decreased from 6.75 (pretrauma) to 4.5 (postoperatively). The
      average Lysholm and subjective IKDC scores were 83 and 77.4, respectively. Two
      patients were graded as B (nearly normal) and six as C (abnormal), according to
      the IKDC knee evaluation form. KT-2000 arthrometry demonstrated that sagittal
      knee laxity was more than 5 mm in all knees (side to side difference). MRI
      demonstrated grade three signal alterations at the repair site of meniscus in
      three patients and signs of cartilage damage in two patients. All patients were
      asymptomatic during daily activities but seven out of eight reported pain or
      effusion after sports. Medial meniscus repair in the ACL-deficient knee is not
      contraindicated. The need of reducing the level of physical activity is
      essential.

PMID- 16967202
TI  - Sclerosing polidocanol injections in mid-portion Achilles tendinosis: remaining
      good clinical results and decreased tendon thickness at 2-year follow-up.
AB  - The short-term results after treatment with sclerosing polidocanol injections
      have been shown to be good in patients with chronic painful mid-portion Achilles
      tendinosis. This study aimed to evaluate the longer-term effects on tendon
      thickness, structure and vascularity, patient satisfaction with treatment, and
      pain during tendon loading activity. Ultrasonography (US) + colour Doppler (CD)
      was used for evaluation of the tendon, and the patients graded the amount of pain
      during tendon loading activity on a VAS. Forty-two patient's tendons (23 men and
      19 women, mean age 53 years) with a long duration (mean 32 months) of pain
      symptoms from mid-portion Achilles tendinosis (US + CD showed a localised
      thickening, structural changes and neovascularisation), were at three (mean)
      occasions (6-8 weeks in between) treated with US and CD guided injections of the
      sclerosing substance polidocanol, targeting the area with neovessels ventral to
      the tendon. After treatment, 37 patients were satisfied with the results of the
      treatment and back to previous (before injury) activity level. At the 2-year
      follow-up (mean 23 months), 38 patients were satisfied with the results of the
      treatment, and there was a significant reduction in VAS (from 75 to 7; P < 0.05).
      US showed a significant reduction in the mean mid-portion tendon thickness (from
      10 to 8 mm, P < 0.05) and a "more normal" structure. CD showed no, or a few,
      remaining neovessels in the majority of the successfully treated tendons. In
      conclusion, treatment with sclerosing polidocanol injections in patients with
      chronic painful mid-portion Achilles tendinosis showed remaining good clinical
      results at a 2-year follow-up. Decreased tendon thickness and improved structure
      after treatment, might indicate a remodelling potential?

PMID- 16967203
TI  - Simultaneous evaluation of circulating chemokine and cytokine profiles in elderly
      subjects by multiplex technology: relationship with zinc status.
AB  - Cellular components of both adaptive and innate immune systems produce different
      chemokines and cytokines, involved in different signalling pathways among cells,
      and modulate effector function during immune response, playing a key role in the
      regulation of the type and extent of the immune response in the elderly. We
      evaluated the circulating concentration of selected chemokines: MCP-1, MIP
      1alpha, IL-8, RANTES together with IL-6 and TNF-alpha in plasma obtained from a
      group of healthy old subjects, in order to highlight possible differences in the
      synthesis of these factors, assuming that both the cytokine and the chemokine
      networks are remodelled with ageing. The simultaneous evaluation was performed by
      a multiplex analysis system. In addition, since micronutrient deficiency may
      underlie an inflammatory response, the association between chemokine levels and a
      nutritional element such as zinc was also evaluated, since the immune system is
      the first system to be affected by changing zinc levels, due to its high cell
      turnover. A progressive age-related increase of plasma concentrations of all
      soluble factors was observed. The increment was particularly evident for IL-6, IL
      8, MCP-1 and TNF-alpha in the over 85-year-old group in concomitance with
      increasing percentages of subjects with low circulating levels of zinc. In
      conclusion, the remodelling of chemokine profiles, skewed to Th2 response by both
      advanced ages and circulating levels of zinc, might reflect different states of
      activation and/or responsiveness of the human immune cell/mediator network, thus
      influencing the ability to develop rapid innate and long-lasting adaptive immune
      responses with advancing age.

PMID- 16967204
TI  - Effect of improved zinc status on T helper cell activation and TH1/TH2 ratio in
      healthy elderly individuals.
AB  - Mild zinc deficiency is a common condition in healthy elderly individuals leading
      to impaired cell-mediated immune response. Here we report the effect of improved
      zinc status on TH1/TH2 balance and on the activation status of T helper cells in
      19 healthy elderly subjects aged 69.8 +/- 5.1 years. Our investigations revealed
      a mild zinc deficiency which was adjusted by oral zinc supplementation for seven
      weeks. Improved serum zinc levels significantly reduced levels of activated T
      helper cells whereas changes in TH1/TH2 ratio (determined by CCR4 and CCR5
      expression) were not observed. These findings suggest that elderly individuals
      may benefit from moderate zinc supplementation due to improved immune response
      leading to reduced incidences of autoimmune diseases and infections.

PMID- 16967205
TI  - Antioxidant enzyme activities in healthy old subjects: influence of age, gender
      and zinc status: results from the Zincage Project.
AB  - Enzymatic activities of plasma superoxide dismutase (pSOD), catalase (CAT) and
      glutathione peroxidase (GPx) and erythrocyte superoxide dismutase (eSOD) were
      assayed in 981 healthy community dwelling old subjects participating in the
      Zincage Project. The relationship between antioxidant enzyme activities and,
      respectively, gender, age and zinc status were assessed. eSOD activity was higher
      in nonagenarians than in 80 year old subjects. Plasma Zn was lower in
      nonagenarians compared with younger subjects. The prevalence of Zn deficiency
      increased with age, with normal Zn levels observed in about 80% of adult subjects
      and only in 37% of the nonagenarians. Women showed higher eSOD and CAT activities
      compared to men, whereas plasma Zn was higher in men than in women. There was a
      positive correlation between eSOD activity and age and a negative correlation
      between eSOD activity and plasma Zn concentrations. An inverse correlation was
      also found between plasma Zn concentration and age. Further studies on different
      aspects of Zn metabolism--intake, plasma concentration, peripheral cell
      concentration, activity and amount of Zn-dependent enzymes--are warranted.

PMID- 16967206
TI  - Homocysteine induces DNA damage and alterations in proliferative capacity of T
      lymphocytes: a model for immunosenescence?
AB  - Homocysteine (Hcy) appears to exert different effects on immune functions
      possibly contributing to age-related pathological states, including vascular
      diseases, immune dysfunction, and Alzheimer's disease. However, molecular
      mechanisms underlying Hcy toxicity need to be better characterized. Since T cells
      are a suitable model to address the possible role of replicative senescence
      during the in vivo aging, we investigated the effects of high Hcy concentrations
      on mitogen-activated lymphocytes, with regard to evaluation of DNA damage and
      cell cycle alterations. Cultured human peripheral blood lymphocytes were
      stimulated with mitogenic concanavalin A (5 microg/ml) for 48 h in the presence
      or absence of Hcy (1 mM). Both flow cytometric analysis and caspase-3 activity
      assay showed an increased rate of apoptosis in Hcy-treated lymphocyte cultures
      compared to controls. Further, Hcy exposure caused DNA fragmentation as evaluated
      by single cell gel electrophoresis showing the occurrence of comets. Cytokinesis
      block micronucleus assay, performed after addition of cytochalasin B (5
      microg/ml) and incubation up to 72 h, revealed a significantly higher frequency
      of micronucleated/binucleated cells in Hcy-treated cultures compared to controls
      (P < 0.001). Hcy also reduced cyclin B expression in comparison to control
      cultures, while cyclin D levels were not significantly affected. Cell cycle
      alterations, such as the inability of cells to enter into mitosis, could be
      related with DNA damage. These findings provided a link between perturbation of
      lymphocyte proliferation homeostasis and commitment towards apoptosis. Our
      results suggest the involvement of Hcy in the altered immune function associated
      with age and disease pathology.

PMID- 16967207
TI  - Carnosine, taurine and enzyme activities of human skeletal muscle fibres from
      elderly subjects with osteoarthritis and young moderately active subjects.
AB  - Ageing is associated with a reduction in muscle carnosine (beta-alanyl-L
      histidine), but there are no data on the changes specifically in type I and type
      II muscle fibres. Given the higher carnosine content of type II fibers, changes
      observed in whole muscle may be secondary to a shift in fibre composition.
      Carnosine, beta-alanine, histidine, taurine, and citrate synthase (CS) and
      glycogen phosphorylase (Phos), were measured in pools of single muscle fibres
      from freeze-dried muscle biopsies of vastus lateralis of nine elderly sedentary
      subjects (65-80 years) with osteoarthritis of the knee and undergoing total knee
      replacement, and nine young moderately active healthy subjects (20-35 years).
      Fibres were characterised as type I or II by myosin ATPase activity. Carnosine
      was 53.2% lower in type II fibres of older subjects resulting in an estimated 7%
      (and most probably still higher) decline in intracellular physico-chemical
      buffering capacity. Younger subjects showed higher CS activities in type I and
      higher Phos activities in type II fibres. These differences were less apparent in
      elderly subjects. Possible causes for the change in the carnosine content are
      reduced physical activity, reduced meat intake, or the result of progressive
      denervation.

PMID- 16967208
TI  - Determination of volatile organic compounds pollution sources in malaysian
      drinking water using multivariate analysis.
AB  - A field investigation was conducted at all water treatment plants throughout 11
      states and Federal Territory in Peninsular Malaysia. The sampling points in this
      study include treatment plant operation, service reservoir outlet and auxiliary
      outlet point at the water pipelines. Analysis was performed by solid phase micro
      extraction technique with a 100 microm polydimethylsiloxane fibre using gas
      chromatography with mass spectrometry detection to analyse 54 volatile organic
      compounds (VOCs) of different chemical families in drinking water. The
      concentration of VOCs ranged from undetectable to 230.2 microg/l. Among all of
      the VOCs species, chloroform has the highest concentration and was detected in
      all drinking water samples. Average concentrations of total trihalomethanes
      (THMs) were almost similar among all states which were in the range of 28.4--33.0
      microg/l. Apart from THMs, other abundant compounds detected were cis and trans
      1,2-dichloroethylene, trichloroethylene, 1,2-dibromoethane, benzene, toluene,
      ethylbenzene, chlorobenzene, 1,4-dichlorobenzene and 1,2-dichloro - benzene.
      Principal component analysis (PCA) with the aid of varimax rotation, and parallel
      factor analysis (PARAFAC) method were used to statistically verify the
      correlation between VOCs and the source of pollution. The multivariate analysis
      pointed out that the maintenance of auxiliary pipelines in the distribution
      systems is vital as it can become significant point source pollution to Malaysian
      drinking water.

PMID- 16967209
TI  - Predicting water quality impaired stream segments using landscape-scale data and
      a regional geostatistical model: a case study in Maryland.
AB  - In the United States, probability-based water quality surveys are typically used
      to meet the requirements of Section 305(b) of the Clean Water Act. The survey
      design allows an inference to be generated concerning regional stream condition,
      but it cannot be used to identify water quality impaired stream segments.
      Therefore, a rapid and cost-efficient method is needed to locate potentially
      impaired stream segments throughout large areas. We fit a set of geostatistical
      models to 312 samples of dissolved organic carbon (DOC) collected in 1996 for the
      Maryland Biological Stream Survey using coarse-scale watershed characteristics.
      The models were developed using two distance measures, straight-line distance
      (SLD) and weighted asymmetric hydrologic distance (WAHD). We used the Corrected
      Spatial Akaike Information Criterion and the mean square prediction error to
      compare models. The SLD models predicted more variability in DOC than models
      based on WAHD for every autocovariance model except the spherical model. The SLD
      model based on the Mariah autocovariance model showed the best fit (r(2) = 0.72).
      DOC demonstrated a positive relationship with the watershed attributes percent
      water, percent wetlands, and mean minimum temperature, but was negatively
      correlated to percent felsic rock type. We used universal kriging to generate
      predictions and prediction variances for 3083 stream segments throughout
      Maryland. The model predicted that 90.2% of stream kilometers had DOC values less
      than 5 mg/l, 6.7% were between 5 and 8 mg/l, and 3.1% of streams produced values
      greater than 8 mg/l. The geostatistical model generated more accurate DOC
      predictions than previous models, but did not fit the data equally well
      throughout the state. Consequently, it may be necessary to develop more than one
      geostatistical model to predict stream DOC throughout Maryland. Our methodology
      is an improvement over previous methods because additional field sampling is not
      necessary, inferences about regional stream condition can be made, and it can be
      used to locate potentially impaired stream segments. Further, the model results
      can be displayed visually, which allows results to be presented to a wide variety
      of audiences easily.

PMID- 16967211
TI  - A multimodal approach in coil embolization of a bile leak following
      cholecystectomy.
AB  - Bile leak is a well-known complication of cholecystectomy. Endoscopic drainage
      and decompression of the biliary system including temporary insertion of a
      biliary stent is generally considered the treatment of choice. We report the
      successful obliteration of a bile leak using fibered platinum coils placed under
      fluoroscopic guidance after stent treatment had failed.

PMID- 16967212
TI  - Tension pneumothorax after placement of a tunneled pleural drainage catheter in a
      patient with recurrent malignant pleural effusions.
AB  - A case of tension pneumothorax developed after placement of a tunneled pleural
      catheter for treatment of malignant pleural effusion in a patient with advanced
      lung cancer. The catheter placement was carried out by an experienced operator
      under direct ultrasound guidance, and the patient showed immediate symptomatic
      improvement with acute decompensation occurring several hours later. Possible
      mechanisms for this serious complication of tunneled pleural catheter placement
      are described, and potential strategies to avoid or prevent it in future are
      discussed.

PMID- 16967213
TI  - The size of gelatin sponge particles: differences with preparation method.
AB  - PURPOSE: To assess whether the size distribution of gelatin sponge particles
      differed according to the method used to make them and the type of original
      sheet. METHODS: Gelatin sponge particles of approximately 1-1.5 x 1-1.5 x 2 mm
      were made from either Spongel or Gelfoam sheets by cutting with a scalpel and
      scissors. Particles were also made of either Spongel or Gelfoam sheets by pumping
      with two syringes and a three-way stopcock. The size distribution of the
      particles in saline was compared among the groups. RESULTS: (1) Cutting versus
      pumping: When Spongel was used, cutting produced lower rates of smaller particles
      < or = 500 microm and larger particles > 2000 microm compared with pumping back
      and forth 30 times (1.1% vs 37.6%, p < 0.0001; 2.2% vs 14.4%, p = 0.008). When
      Gelfoam was used, cutting produced lower rates of smaller and larger particles
      compared with pumping (8.5% vs 20.4%, p = 0.1809; 0% vs 48.1%, p < 0.0001). (2)
      Spongel versus Gelfoam: There was no significant difference in the size
      distribution of the particles between Spongel and Gelfoam (p = 0.2002) when
      cutting was used. CONCLUSION: The size distribution of gelatin sponge particles
      differed according to the method used to make them. More uniform particle sizes
      can be achieved by cutting than by pumping.

PMID- 16967214
TI  - Contribution of transjugular liver biopsy in patients with the clinical
      presentation of acute liver failure.
AB  - PURPOSE: Acute liver failure (ALF) treated with conservative therapy has a poor
      prognosis, although individual survival varies greatly. In these patients, the
      eligibility for liver transplantation must be quickly decided. The aim of this
      study was to assess the role of transjugular liver biopsy (TJLB) in the
      management of patients with the clinical presentation of ALF. METHODS: Seventeen
      patients with the clinical presentation of ALF were referred to our institution
      during a 52 month period. A TJLB was performed using the Cook Quick-Core needle
      biopsy. Clinical data, procedural complications, and histologic findings were
      evaluated. RESULTS: Causes of ALF were virus hepatitis B infection in 7 patients,
      drug toxicity in 4, mushroom in 1, Wilson's disease in 1, and unknown origin in
      4. TJLB was technically successful in all patients without procedure-related
      complications. Tissue specimens were satisfactory for diagnosis in all cases. In
      14 of 17 patients the initial clinical diagnosis was confirmed by TJLB; in 3
      patients the initial diagnosis was altered by the presence of unknown cirrhosis.
      Seven patients with necrosis < 60% were successfully treated with medical
      therapy; 6 patients with submassive or massive necrosis (> or = 85%) were treated
      with liver transplantation. Four patients died, 3 had cirrhosis, and 1 had
      submassive necrosis. There was a strict statistical correlation (r = 0.972, p <
      0.0001) between the amount of necrosis at the frozen section examination and the
      necrosis found at routine histologic examination. The average time for TJLB and
      frozen section examination was 80 min. CONCLUSION: In patients with the clinical
      presentation of ALF, submassive or massive liver necrosis and cirrhosis are
      predictors of poor prognosis. TLJB using an automated device and frozen section
      examination can be a quick and effective tool in clinical decision-making,
      especially in deciding patient selection and the best timing for liver
      transplantation.

PMID- 16967215
TI  - Intermittent hepatic vein balloon occlusion during radiofrequency ablation in the
      liver.
AB  - The purpose of the study was to assess the feasibility of intermittent hepatic
      vein balloon occlusion during percutaneous radiofrequency (RF) ablation. Eight
      non-anticoagulated patients who had primary (n = 2) and metastatic (n = 6) liver
      tumors with a mean diameter of 4.2 cm (range 2.4-6.5 cm) were treated, resulting
      in a mean ablation diameter of 6.3 cm (range 4.3-9.3 cm). Six of 9 (67%) of the
      balloon-occluded hepatic veins were patent. No clinical sequelae of thrombosis
      were noted. Mean length of follow-up with CT and/or MRI was 12 months. Local
      tumor control was achieved in 5 of 8 patients. Intermittent hepatic vein balloon
      occlusion could potentially be a low-risk adjunctive maneuver for thermal
      ablation therapy in the treatment of large tumors and tumors adjacent to large
      vessels.

PMID- 16967216
TI  - Spontaneous retroperitoneal hemorrhage from adrenal artery aneurysm.
AB  - Spontaneous adrenal hemorrhage is a very rare but serious disorder of the adrenal
      gland that can require emergent treatment. We report on a 42-year-old man who
      underwent selective angiography for diagnosis and treatment of retroperitoneal
      hemorrhage from small adrenal artery aneurysm. This case gives further details
      about the value of transluminal artery embolization in the management of visceral
      aneurysm rupture.

PMID- 16967217
TI  - Outcomes of endovascular abdominal aortic aneurysm repair in patients with
      hostile neck anatomy.
AB  - PURPOSE: The principal anatomic contraindication to endovascular aneurysm repair
      (EVR) is an unfavorable proximal aortic neck. With increasing experience, a
      greater proportion of patients with unfavorable neck anatomy are being offered
      EVR. This study aimed to evaluate outcomes in patients with challenging proximal
      aortic neck anatomy. METHODS: Prospectively collected data from 147 consecutive
      patients who underwent EVR between December 1997 and April 2005 were supplemented
      with a retrospective review of medical records and radiological images.
      Unfavorable anatomic features were defined as neck diameter >28 mm, angulation
      >60 degrees, circumferential thrombus >50%, and length <10 mm. Eighty-seven
      patients with 0 adverse features (good necks) were compared with 60 patients with
      one or more adverse features (hostile necks). RESULTS: Comparing the good neck
      with the hostile neck group, there were no significant differences in the
      incidence of primary technical success (p = 0.15), intraoperative adjunctive
      procedures (p = 0.22), early proximal type I endoleak (<30 days) (p = 1.0), late
      proximal type I endoleak (>30 days) (p = 0.57), distal type I endoleak (p =
      0.40), type III endoleak (p = 0.51), secondary interventions (p = 1.0), aneurysm
      sac expansion (p = 0.44), or 30 day mortality (p = 0.70). The good neck group had
      a significantly increased incidence of type II endoleak (p = 0.023). By
      multivariate analysis, the incidence of intraoperative adjunctive procedures was
      significantly increased in the presence of severe angulation (p = 0.041, OR 3.08,
      95% CI 1.05-9.04). CONCLUSION: Patients with severely hostile proximal aortic
      neck anatomy may be treated with EVR, although severely angulated necks require
      additional intraoperative procedures. Early outcomes are encouraging and suggest
      that indications for EVR may be expanded to include patients with hostile neck
      anatomy.

PMID- 16967218
TI  - New embolization microcoil consisting of firm and flexible segments: preliminary
      clinical experience.
AB  - PURPOSE: To describe the preliminary clinical experience with a new embolization
      microcoil. METHODS: The microcoil was made of a platinum coil spring, and
      consisted of firm and flexible segments. The firm segment functioned as an anchor
      and the flexible segment was well compacted to occlude the arteries. No Dacron
      fiber was attached. Seventy-one new microcoils were placed via microcatheters in
      28 visceral arteries of 17 patients. Two other types of microcoils with Dacron
      fibers were used together in 8 arteries. RESULTS: Sixty-nine new microcoils were
      placed and compacted successfully. Two coils were misplaced; one was retrieved
      and the other was left in the migrated artery, which remained patent 5 months
      later. All 28 arteries were occluded, and the goals of intervention were achieved
      successfully in all 17 cases. CONCLUSION: The new microcoils anchored and
      compacted well in the arteries. The clinical feasibility of this coil design was
      confirmed. The additional use of other types of microcoils with Dacron fiber was
      necessary to obtain rapid occlusion in some cases.

PMID- 16967219
TI  - Percutaneous transcatheter embolization of a large pulmonary arteriovenous
      fistula with an Amplatzer vascular plug.
AB  - Percutaneous transcatheter embolization has become the treatment of choice for
      pulmonary arteriovenous fistulas (PAVFs), in most cases replacing surgical
      intervention. However, while "classic" devices, such as intravascular coils and
      detachable balloons, have proved to be successful for interventional occlusions
      of small or medium-sized PAVFs, they are not ideal in larger fistulas because of
      the risk for embolization to the systemic circulation. We describe the case of a
      61-year-old woman with a symptomatic huge solitary pulmonary arteriovenous
      fistula (4.5 cm in diameter), occupying part of the lung in the lower right lobe
      with two feeding arteries (10 and 4 mm in diameter, respectively), who underwent
      successful transcatheter closure with an Amplatzer Vascular Plug, a new device
      designed for the occlusion of vascular abnormalities.

PMID- 16967220
TI  - Catheter-directed thrombolysis with percutaneous rheolytic thrombectomy versus
      thrombolysis alone in upper and lower extremity deep vein thrombosis.
AB  - PURPOSE: To compare the efficacy of catheter-directed thrombolysis (CDT) alone
      versus CDT with rheolytic percutaneous mechanical thrombectomy (PMT) for upper
      and lower extremity deep vein thrombosis (DVT). METHODS: A retrospective cohort
      of consecutive patients with acute iliofemoral or brachiosubclavian DVT treated
      with urokinase CDT was identified, and a chart review was conducted. Demographic
      characteristics, treatment duration, total lytic dose, clot lysis rates and
      complications were compared in patients treated with urokinase CDT alone or
      combined CDT and rheolytic PMT. RESULTS: Forty limbs in 36 patients were treated
      with urokinase CDT alone. Twenty-seven limbs in 21 patients were treated with
      urokinase CDT and rheolytic PMT. The mean treatment duration for urokinase CDT
      alone was 48.0 +/- 27.1 hr compared with 26.3 +/- 16.6 hr for urokinase CDT and
      rheolytic PMT (p = 0.0004). The mean urokinase dose required for CDT alone was
      5.6 +/- 5.3 million units compared with 2.7 +/- 1.8 million units for urokinase
      CDT with rheolytic PMT (p = 0.008). Complete clot lysis was achieved in 73%
      (29/40) of DVT treated with urokinase CDT alone compared with 82% (22/27) treated
      with urokinase CDT with rheolytic PMT. CONCLUSION: Percutaneous CDT with
      rheolytic PMT is as effective as CDT alone for acute proximal extremity DVT but
      requires significantly shorter treatment duration and lower lytic doses.
      Randomized studies to confirm the benefits of pharmacomechanical thrombolysis in
      the treatment of acute proximal extremity DVT are warranted.

PMID- 16967221
TI  - Treatment of a celiac trunk aneurysm close to the hepato-splenic bifurcation by
      using hepatic stent-graft implantation and splenic artery embolization.
AB  - We present a case of a 73-year-old man in whom a celiac trunk aneurysm close to
      the hepato-splenic bifurcation was discovered and treated by using celiac-hepatic
      stent-grafts implantation and splenic artery embolization.

PMID- 16967222
TI  - Catheter-directed thrombolysis of acute deep vein thrombosis in the lower
      extremity of a child with interrupted inferior vena cava.
AB  - We present the case of a 14-year-old girl who developed acute deep vein
      thrombosis (DVT) in her right lower extremity. Laboratory testing revealed
      protein S deficiency, and the patient's father also had this abnormality with a
      history of lower extremity DVT. Manual thromboaspiration followed by catheter
      directed thrombolysis resulted in total clearance of all thrombi. Computed
      tomography and later venography revealed an interrupted inferior vena cava.
      Catheter-directed thrombolysis is an established treatment for adults with acute
      DVT. To the best of our knowledge, this report is the first to describe catheter
      directed thrombolysis in a pediatric patient with lower extremity DVT. Our
      results suggest that catheter-directed thrombolysis is safe and effective for use
      in selected older children and adolescents with acute DVT in the lower extremity.

PMID- 16967223
TI  - Fatal peritoneal bleeding following embolization of a carotid-cavernous fistula
      in Ehlers-Danlos syndrome type IV.
AB  - We report the case of a 25-year-old woman treated for a spontaneous carotid
      cavernous fistula in a context of Ehlers-Danlos syndrome type IV. Embolization
      with a transvenous approach was achieved without complications; however, the
      patient died 72 hr later of massive intraperitoneal bleeding. At autopsy, no
      lesion of the digestive arteries was identified. Possible causes of this bleeding
      are discussed.

PMID- 16967224
TI  - Stent-grafts in the management of hemorrhagic complications related to hemostatic
      closure devices: report of two cases.
AB  - We report 2 cases of hemorrhagic complications related to use of the Angio-Seal
      hemostatic closure device that were successfully managed with stent-grafts. Two
      patients with subarachnoid hemorrhage were referred to our departments for
      endovascular treatment of ruptured intracranial aneurysms. The treatment was
      performed through a femoral access; the sheaths were removed immediately after
      the procedures, and the punctures sites closed by Angio-Seals. Both patients
      presented clinical signs of hypovolemic shock after treatment. The diagnosis of
      active bleeding through the puncture site was made by emergency digital
      subtraction angiography. The lesions were managed with stent-grafts. The use of
      stent-grafts proved to be efficient in the management of these life-threatening
      hemorrhagic complications following the use of the Angio-Seal hemostatic closure
      device.

PMID- 16967225
TI  - Complications of endovascular repair of abdominal aortic aneurysms: a review.
AB  - The endovascular procedure for repair of abdominal aortic aneurysms has had an
      enormous impact on the treatment of this challenging disease. Complications,
      however, do occur and it is important to have a thorough understanding of the
      array of complications and appropriate management strategies. In this review of
      endovascular complications, we describe early and late complications paying
      particular attention to preventive, treatment and surveillance strategies.

PMID- 16967226
TI  - The potential role of optical coherence tomography in the evaluation of
      vulnerable carotid atheromatous plaques: a pilot study.
AB  - PURPOSE: The decision to intervene surgically in patients with carotid artery
      disease is based on the presence of symptoms, along with the severity of carotid
      artery stenosis as assessed by ultrasound or X-ray computed tomography (CT).
      Optical coherence tomography (OCT) is a relatively new imaging technique that
      offers potential in the identification of, as well as the distinction between,
      stable and unstable atherosclerotic plaques. The purpose of our study was to
      evaluate whether OCT can be used as a noninvasive diagnostic tool to reveal the
      morphology of carotid stenosis from the adventitial surface of the carotid
      artery. To achieve this aim, excised atheromatous plaques were scanned by OCT
      from the external surface. METHODS: Plaques removed at carotid endarterectomy
      were scanned by OCT from the external surface within 72 hr of surgery and then
      examined histologically. The images of the histologic slides and the scans were
      then compared. RESULTS: We examined 10 carotid endarterectomy specimens and were
      able to identify calcification, cholesterol crystal clefts, and lipid deposits in
      the OCT images with histologic correlation. The strong light scattering from the
      calcified tissue and cholesterol crystal clefts limited the depth of light
      penetration, making observation of the intimal surface and the detail of the
      fibrous cap difficult. However, we were able to confidently identify the absence
      of an atherosclerotic plaque by OCT scans even from the external surface.
      CONCLUSION: The results of this pilot study demonstrate that OCT can reveal the
      main features of carotid stenosis but that plaque vulnerability cannot be
      reliably and precisely assessed if scanned from the external surface with OCT in
      its present form.

PMID- 16967228
TI  - Spectrum of the inferior vena cava: MDCT findings.
AB  - Inferior vena cava (IVC) abnormalities are not uncommon. Congential anomalies,
      thrombosis, neoplasms, and obstructive lesions can involve IVC. With the wide use
      of multidetector CT, it has demonstrated its ability to display the abnormalities
      of IVC. Congenital anomalies, thrombosis, neoplasms, and stenosis or obstructive
      diseases and other abnormalities can be demonstrated by MDCT. We present a
      pictorial essay to illustrate its roles in detecting and defining the nature of
      lesions of IVC, from the anatomy to disease spectrum of IVC.

PMID- 16967229
TI  - Extravascular incidental findings at multislice CT angiography of the abdominal
      aorta and lower extremity arteries: a retrospective review study.
AB  - PURPOSE: To assess the frequency and clinical impact of extravascular incidental
      findings on routine CT angiography of abdominal aorta or lower extremity
      arteries. MATERIALS AND METHODS: From January 2002 to July 2004, a total of 692
      patients underwent CT angiography of abdominal aorta and lower extremity
      arteries. Two radiologists retrospectively reviewed by consensus cross-sectional
      images for the presence and clinical impact definition of extravascular findings.
      The revision of hospital charts, medical records, and all procedures' reports
      performed before and after CT angiography represented the standard of reference
      (SOR). RESULTS: Only 373 out of 605 patients in whom extravascular findings were
      found had a SOR; in these patients CT angiography obtained a true-positive
      incidental rate of 98.9% (369/373). For the clinical impact definition of CT
      angiography incidental findings, a concordance with SOR was obtained in 56.3% of
      patients, whereas a subsequent investigation was required in 183 patients
      (183/369, 49.6%). Among clinically relevant incidental findings, a total of 35
      malignancies (35/894, 3.9%) were detected in 20 patients (20/423, 4.7%); in 15
      patients (15/423, 3.5%) malignancy was unknown before CT-angiography exam.
      CONCLUSIONS: A careful observation of cross-sectional images, even if "time
      consuming", is mandatory not only to assess vascular findings but also to avoid a
      misdiagnosis of clinical relevant extravascular findings.

PMID- 16967238
TI  - Crohn disease of small bowel: multidetector row CT with CT enteroclysis, dynamic
      contrast enhancement, CT angiography, and 3D imaging.
AB  - BACKGROUND: CT could be used to evaluate abnormalities in the bowel wall,
      mesentery, adjacent structures, vasculature, and even the activity of Crohn
      disease (CD). To our knowledge, few direct comparisons of CD characterization
      using multidetector row CT with dynamic contrast enhancement, 3D imaging, CT
      angiography (CTA), and CT-enteroclysis (CT-E) on the same cohort of patients. The
      purpose of this study was to evaluate the diagnostic value of CD using
      multidetector helical CT with CT-E, dynamic contrast enhancement, 3D imaging, and
      CTA. METHODS: Twenty-eight patients known or suspected CD underwent CT-E, dynamic
      contract enhancement, CTA, and 3D imaging. The multidetector CT series images
      were performed on eight-slice CT scanner. All the examinations were performed
      when water was used as an oral contrast starting 25 s after 140 mL of intravenous
      contrast agent was administered, followed by portal venous phase (60 s), and a 60
      70 s delay, then sending 1.25-mm slices to the 3D workstation, CT angiograms and
      3D images were reconstructed. All the images were reviewed to detect
      abnormalities of CD. The abnormalities of the bowel wall, mucosal and submucosal
      ulceration, prominent perienteric vasculature, sinus tracts or fistulae, abscess
      were evaluated. RESULTS: Crohn disease was diagnosed in 28 patients by CT images,
      and 54 inflammatory segments were revealed. In active inflammatory cases, the
      diseased bowel wall thickened and the enhancement of diseased bowel wall
      increased significantly in 34 inflammatory segments of 22 cases, the enhancement
      of diseased bowel wall increased significantly but without the wall thickened in
      three patients. Prominent vasculature was found in CTA and 3D images in 21
      patients with active diseases. In 16 patients, the sharp interface between bowel
      and mesentery was lost and the attenuation of fat increased. Sinus tracts or
      fistulae were observed in eight patients, four of 28 patients demonstrated
      abscesses, all were active inflammatory patients. In three chronic inflammatory
      patients, normal bowel, bowel lumen stricture, and the normal enhancement of the
      wall were displayed. CONCLUSION: The abnormalities of CD and its complications
      can be identified by multidetector CT with CT-E, dynamic enhancement, CTA, and 3D
      imaging, and they are important methods in diagnosing CD. Complications of CD can
      be shown better when CT-E is performed.

PMID- 16967239
TI  - Adult celiac disease: MRI findings.
AB  - The purpose of our report is to describe a spectrum of findings of celiac disease
      at MR enterography. MR enterography is a non-invasive, feasible, and reproducible
      imaging technique for the evaluation of small bowel. Findings on MR enterography,
      similar to those of conventional barium studies, may suggest a diagnosis of
      celiac disease.

PMID- 16967240
TI  - Staging rectal cancer: MRI compared to MDCT.
AB  - PURPOSE: To audit the accuracy with which pre-operative MRI and multi-detector
      row CT determine the relationship between rectal tumour and the circumferential
      resection margin (CRM). MATERIALS AND METHODS: The MR and CT scans of 72 patients
      with rectal adenocarcinoma were retrieved. The relationship between tumour and
      the mesorectal fascia was determined by two observers, who classified appearances
      into three categories: no tumour within 5 mm of the mesorectal fascia; tumour
      within 5 mm of the mesorectal fascia ('threatened' margin); tumour at the
      mesorectal fascia ('involved' margin). Agreement with post-operative
      histopathology was assessed by Kappa statistics. RESULTS: There was poor
      agreement between both MRI and CT, and post-operative histology, both in all 72
      patients and in the 42 who had received no pre-operative therapy or short-course
      radiotherapy only. Both imaging modalities had a tendency to overstage patients
      whose CRM was uninvolved subsequently. However, the negative predictive value for
      an uninvolved margin was 81.8% by MRI and 84.6% by CT. There was no patient with
      an involved margin by histopathology whose imaging had suggested the margin was
      uninvolved. CONCLUSION: Both pre-operative MRI and multi-detector row CT have
      high negative predictive values for a subsequently uninvolved resection margin.

PMID- 16967241
TI  - Diagnosis of intrahepatic and common duct stones: combined unenhanced and
      contrast-enhanced helical CT in 1090 patients.
AB  - BACKGROUND: We determined the accuracy of combined unenhanced and contrast
      enhanced helical computed tomography (CT) for diagnosis of bile duct stones.
      METHODS: During a 12-month period, 1090 patients who underwent combined CT and
      endoscopic retrograde cholangiography (ERC) or percutaneous transhepatic
      cholangioscopy (PTC) were enrolled in this study. The results of prospective CT
      interpretation regarding the presence of bile duct stones were compared with
      results of endoscopic stone removal, PTC and with surgical results. In 70
      patients, detectability of stones on CT was evaluated depending on stone types.
      RESULTS: Of 1090 study patients, 175 and 299 patients were confirmed to have
      intrahepatic and common duct stones, respectively. The sensitivity and
      specificity of combined CT were 73% and 98% for diagnosis of intrahepatic stones
      and 71% and 97% for common duct stones. Of 70 patients 24, 25, and 21 patients
      had cholesterol, black pigment, and brown pigment stones, respectively. Eleven of
      24 cholesterol stones, 21 of 25 black pigment stones, and 15 of 21 brown pigment
      stones were detected on combined CT. CONCLUSION: Combined CT is of limited
      sensitivity for detection of bile duct stones, especially in Western countries
      where cholesterol stones predominate. It may be of greater value in populations
      with a higher incidence of pigment stones. Other complementary imaging modalities
      are needed for patients with negative CT findings who are highly suspected to
      have biliary stones.

PMID- 16967242
TI  - Acute mesenteric ischemia: endovascular therapy.
AB  - Acute mesenteric ischemia (AMI) is an abdominal emergency with a high mortality.
      Prompt revascularization can prevent intestinal infarction and reduce mortality.
      We report three cases of acute occlusive mesenteric ischemia without signs of
      intestinal necrosis, which were successfully managed with endovascular
      interventions. Mechanical thrombus fragmentation was performed and underlying
      chronic stenoses were treated with stent implantation. All the patients had pain
      relief immediately after the procedure, and none of them required surgery for
      bowel resection. The patients remained symptom free during a follow-up of 12-16
      months. We suggest that endovascular treatment is a feasible option in patients
      with AMI and can prevent intestinal infarction.

PMID- 16967243
TI  - Gastric hepatoid adenocarcinoma: CT findings.
AB  - BACKGROUND: In this study, we evaluated the CT findings of patients with hepatoid
      adenocarcinoma of the stomach. METHODS: The CT scans of eight patients (seven
      males and one female; age range 44-70 years; mean age 59 years) with
      histologically proven hepatoid adenocarcinoma of the stomach were retrospectively
      evaluated by two radiologists in consensus. Scans were evaluated for gastric wall
      thickening, involved site enhancement, adjacent organ invasion, lymphadenopathy,
      distant metastases, and venous tumor thrombosis. RESULTS: Tumors appeared as
      eccentric wall thickening (n = 8) and heterogeneous enhancement (n = 7). Adjacent
      organ invasions were noted to liver (n = 3), pancreas (n = 2), and esophagus (n =
      1). All eight patients had a regional lymphadenopathy larger than 8 mm in its
      short axis. Distant metastases (liver, n = 4; non-regional lymph node, n = 1)
      were also noted. Venous tumor thrombosis was identified in the portal vein (n =
      3), splenic vein (n = 1), main portal vein (n = 1), or right gastroepiploic vein
      (n = 1) in the regions near primary gastric tumors or metastatic masses.
      CONCLUSION: On CT scans, hepatoid adenocarcinoma of the stomach appears as an
      eccentric gastric wall thickening and shows a strong tendency for liver and lymph
      node metastasis and venous invasion around the primary gastric tumor or a
      metastatic hepatic mass.

PMID- 16967246
TI  - Utility of multidetector CT in the diagnosis of gastric bare area invasion by
      proximal gastric carcinoma.
AB  - PURPOSE: To investigate the utility of multidetector CT (MDCT) in the diagnosis
      of gastric bare area (GBA) invasion by proximal gastric carcinoma (PGC). METHODS:
      Sixty-eight consecutive patients with biopsy-proven PGC underwent MDCT scan prior
      to gastrectomy. We evaluated the CT images separately for the site, size, depth,
      lymph node, and enhancement characteristic of each case. Each postsurgical
      stomach specimen was axially sectioned and comparison was made to determine the
      correlation between the CT findings and the pathological examination of each
      tumor bearing slice. RESULTS: The sensitivity for detecting GBA involvement in
      patients with PGC was 84%. MDCT correctly identified 32 of 38 patients with GBA
      invasion and 10/13 (77%) tumors with metastatic lymph node greater than 5 mm in
      GBA or subphrenic retroperitoneal space. 33/36 (92%) patients with tumor
      extension within the edge of the gastric wall and 28/32 (88%) patients with tumor
      infiltration into subphrenic fat were correctly identified. MDCT correctly
      predicted the infiltration of tumor into the diaphragm in all 14 patients and
      identified 6/11 (55%) patients with gastrophrenic ligament invasion. CONCLUSION:
      MDCT may be of value in assessing the important radiological characteristics of
      GBA invasion in patients with PGC.

PMID- 16967247
TI  - Collateral branches IPMTs: secretin-enhanced MRCP.
AB  - Recently, the fantastic evolution of imaging modalities (especially MR, MDCT,
      EUS) has raised many issues regarding the correct classification of smaller and
      smaller lesions, their preoperative evaluations, and indications of most
      appropriate treatment. However, it is still debated which technique should be
      employed for the diagnosis and the follow-up of intraductal papillary mucinous
      tumours (IPMTs). Despite the superb spatial resolution of MDCT, nowadays most of
      the authors agree on considering MR with magnetic resonance
      cholangiopancreatography (MRCP) the imaging modality of choice in studying IPMTs.
      In particular, MRCP is rapid, non-invasive, and accurate in detecting,
      localizing, and correctly classifying IPMT. The diagnostic performance of MRCP is
      even improved after the introduction of secretin stimulation. In fact, dynamic
      MRCP studies after secretin administration, besides facilitating the depiction of
      the structural characteristics of the lesions, make easier the detection of the
      communicating duct of branch duct IPMTs with the main pancreatic duct, especially
      if the newest high resolution 3D heavily T2-weighted sequences are utilized.
      Secretin stimulation is also useful in the demonstration of early changes of
      associated chronic pancreatitis. Consequently, we believe that secretin-enhanced
      MRCP is the most suitable imaging modality in the diagnosis and follow-up of
      IPMTs of the collateral branches.

PMID- 16967248
TI  - Thrombosed interrupted inferior vena cava and retroaortic left renal vein
      mimicking retroperitoneal neoplasm.
AB  - Anomalies of the inferior vena cava (IVC) have been recognized as one of the
      predisposing factors for deep vein thrombosis. Rarely, thrombosis of an anomalous
      retroperitoneal vein may resemble a soft tissue mass. Awareness of this fact
      helps preventing unnecessary interventions. We report a case of thrombosis of
      retroaortic left renal vein and interrupted IVC that mimicked a retroperitoneal
      neoplasm.

PMID- 16967249
TI  - CT colonography: surveillance in patients with a history of colorectal cancer.
AB  - Colorectal cancer is a leading cause of morbidity and mortality in the United
      States. It is also a disease that is preventable if precursor adenomatous polys
      are removed. Once a diagnosis of colorectal cancer is made, surgical resection is
      the only means of cure. The ability to resect colorectal cancer for cure is
      largely dependent upon the stage of tumor at presentation. Once a patient has
      been treated for colorectal cancer with surgery and in some cases neo-adjuvant or
      adjuvant therapy, they will present for follow-up. Surveillance is performed on
      these patients in order to detect local recurrence that if detected early can be
      surgically resected for cure. Surveillance also allows detection of distant
      metastatic disease that may in some cases also be cured with resection. Finally,
      surveillance of the remaining colon is important to detect the development of new
      or metachronous adenomatoid polyps that if left in place could develop into new
      colon cancers. Imaging can play a part in patient surveillance to detect
      recurrent disease at extracolonic sites as well as the development of new colonic
      lesions. CT colonography is a promising tool for surveillance in patients with a
      history of colorectal cancer.

PMID- 16967251
TI  - Diverticulitis of the small bowel: CT diagnosis.
AB  - In contrast with their colonic equivalents, noncolonic diverticula of the gastro
      intestinal tract are much rarer and an uncommon site of inflammation. Symptoms
      and signs are generally nonspecific and before the advent and development of CT,
      clinical and radiological diagnosis was very difficult. As a result laparotomy
      was carried out in most cases without correct preoperative diagnosis. We report
      three rare cases of noncolonic diverticulitis, respectively, affecting the
      duodenum, the jejunum, and the distal ileum. MDCT with multiplanar
      reconstructions revealed unambiguously diagnostic features in the three cases and
      allowed minimally invasive endoscopic drainage in the duodenal case and
      successful conservative medical treatment in the jejunal and ileal cases. We
      discuss and review the prevalence, physiopathology, symptoms, and complications
      of diverticula of the duodenum and jejuno-ileum and emphasis on the high
      performance of MDCT for the diagnosis of acute diverticular complications.

PMID- 16967250
TI  - Biliary atresia in infants with prolonged cholestatic jaundice: diagnostic
      accuracy of hepatobiliary scintigraphy.
AB  - BACKGROUND: Cholestatic jaundice during infancy is one of the most problematic
      challenges for pediatricians. Biliary atresia (BA) and neonatal hepatitis
      syndrome (NHS) are major causes of cholestatic jaundices. Our aim was to compare
      the diagnostic accuracy of hepatobiliary scintigraphy with liver biopsy and
      ultrasonography in excluding BA. METHODS: Seventy consecutive patients, all
      suffering from prolonged cholestatic jaundice (>1 month), were included.
      Laparotomy with surgical cholangiography was considered as the gold standard;
      however, in nine patients, based on the patient's recovery from jaundice and the
      normalization of laboratory values during the clinical follow-up period (=6-12
      months), the diagnosis of NHS was verified and performing laparotomy was
      unnecessary. All patients underwent hepatobiliary scintigraphy, liver biopsy and
      ultrasonography and their results were compared. RESULTS: Based on the gold
      standards mentioned above, 46 patients (46/70 = 65.7%) had BA. The sensitivity,
      specificity, PPV, NPV, and accuracy of the hepatobiliary scintigraphy in
      diagnosis of BA were 90%, 80%, 91.8%, 76.2%, and 84.5%, respectively. The
      respective values for liver biopsy were 92.5%, 88.9%, 94.9%, 84.2%, and 90.1% and
      for ultrasonographic analysis were 41.7%, 90.9%, 90.9%, 41.7%, and 66.3%.
      CONCLUSION: Hepatobiliary scintigraphy is an important imaging technique in the
      diagnostic evaluation of infants with prolonged cholestatic jaundice. It is a
      convenient and reliable method of differentiating BA from NHS, with a diagnostic
      accuracy superior to that of US but slightly inferior to that of liver biopsy.
      Ultrasonography is the least sensitive and specific available modality and its
      findings should be confirmed by scintigraphy or liver biopsy.

PMID- 16967252
TI  - CT depiction of small arteries in the pancreatic head: assessment using coronal
      reformatted images with 16-channel multislice CT.
AB  - BACKGROUND: To assess the capabilities of 16-channel multislice CT in acquiring
      almost exclusively arterial-phase images of the pancreas and depicting small
      pancreatic arteries in coronal reformatted images. MATERIALS AND METHODS: In 45
      consecutive patients, arterial-phase contrast enhancement was measured in the
      aorta and its branches, portal venous system, and pancreas. Coronal reformatted
      images of 1.2- or 1.3-mm slice thickness at 0.8- or 0.9-mm intervals were
      generated from axial images acquired with 0.5-mm collimation. Two radiologists
      evaluated the quality of imaging in the arterial phase and the visibility of the
      pancreatic arteries in coronal reformatted images. RESULTS: Mean enhancement in
      the aorta and its branches was greater than 300 HU, while that in the portal
      venous system and pancreas was less than 100 HU. The images were judged to be
      suitable for delineating the pancreatic arteries in all patients. The following
      arteries were visualized: anterior superior pancreaticoduodenal (39 patients),
      posterior superior pancreaticoduodenal (41), anterior inferior
      pancreaticoduodenal (39), posterior inferior pancreaticoduodenal (33), dorsal
      pancreatic (42), its right branch (34), and transverse pancreatic (37).
      CONCLUSION: Multislice CT can depict small pancreatic arteries using coronal
      reformatted images generated from almost exclusively arterial-phase axial images
      acquired with 0.5-mm collimation.

PMID- 16967253
TI  - Vascular complications after liver transplantation: evaluation with Doppler US.
AB  - PURPOSE: To demonstrate the spectral and color Doppler ultrasonography (US)
      findings that would indicate vascular complications after liver transplantation
      and to report our single center results of vascular complications detected in
      liver transplant recipients. MATERIALS AND METHODS: Our study was consisted of
      326 patients who underwent liver transplantation procedures between November 1997
      and May 2004. The records of all patients were reviewed retrospectively for the
      details of each patient's post-transplant Doppler US examinations, visceral
      angiographic examinations, and/or surgical procedures. Doppler US findings were
      correlated with angiographic results or surgery. Sensitivity and specificity of
      Doppler US parameters for the diagnosis of vascular complications of the hepatic
      artery, portal vein, and hepatic veins were calculated. RESULTS: Vascular
      complications occurred in 47 patients (14%). Eight instances of vascular
      complications were detected intraoperatively by Doppler US at the time of
      transplantation. For hepatic artery complications, use of a Doppler US criteria
      resulted in a sensitivity and a specificity of 92% and 97%, respectively. Doppler
      US parameters also resulted in a sensitivity and a specificity of 100% in
      detecting portal vein complications, and resulted in a sensitivity of 99% and a
      specificity of 100% in detecting hepatic vein complications. CONCLUSION: Although
      it is clear that Doppler US evaluation is an effective choice for diagnosing
      vascular complications after liver transplantation, we also observed that Doppler
      US examination plays an important role in detecting vascular complications
      intraoperatively and improving the patient's chance for a successful outcome.

PMID- 16967254
TI  - Cowper's syringocele in an adult.
AB  - Cowper's syringocele is cystic dilatation of the excretory bulbourethral gland
      duct. It is an uncommon condition and is usually reported in children. There are
      only ten previous case reports of late presentation in adulthood to the best of
      our knowledge. We present the imaging findings of such a case manifesting at 30
      years of age.

PMID- 16967256
TI  - Nodal staging in genitourinary cancers.
AB  - In patients with genitourinary cancers nodal staging is an integral part of the
      pretreatment evaluation. The presence of nodal metastatic disease plays an
      important role in predicting prognosis and treatment planning. Although some
      nodal groups can be evaluated clinically, most patients undergo various imaging
      studies for nodal staging. Each modality has its own unique attributes and
      applications. This article reviews various imaging modalities, namely, contrast
      enhanced computerized tomography, magnetic resonance imaging (MRI), and positron
      emission tomography, used for nodal staging in patients with genitourinary
      cancers and highlights their strengths and weaknesses. Emerging novel techniques
      such as lymphotropic nanoparticle enhanced MRI are also highlighted.

PMID- 16967257
TI  - An optimization algorithm for a distributed-loop model of an avian urine
      concentrating mechanism.
AB  - To better understand how the avian kidney's morphological and transepithelial
      transport properties affect the urine concentrating mechanism (UCM), an inverse
      problem was solved for a mathematical model of the quail UCM. In this model, a
      continuous, monotonically decreasing population distribution of tubes, as a
      function of medullary length, was used to represent the loops of Henle, which
      reach to varying levels along the avian medullary cones. A measure of
      concentrating mechanism efficiency - the ratio of the free-water absorption rate
      (FWA) to the total NaCl active transport rate (TAT) - was optimized by varying a
      set of parameters within bounds suggested by physiological experiments. Those
      parameters include transepithelial transport properties of renal tubules, length
      of the prebend enlargement of the descending limb (DL), DL and collecting duct
      (CD) inflows, plasma Na(+) concentration, length of the cortical thick ascending
      limbs, central core solute diffusivity, and population distribution of loops of
      Henle and of CDs along the medullary cone. By selecting parameter values that
      increase urine flow rate (while maintaining a sufficiently high urine-to-plasma
      osmolality ratio (U/P)) and that reduce TAT, the optimization algorithm
      identified a set of parameter values that increased efficiency by approximately
      60% above base-case efficiency. Thus, higher efficiency can be achieved by
      increasing urine flow rather than increasing U/P. The algorithm also identified a
      set of parameters that reduced efficiency by approximately 70% via the production
      of a urine having near-plasma osmolality at near-base-case TAT. In separate
      studies, maximum efficiency was evaluated as selected parameters were varied over
      large ranges. Shorter cones were found to be more efficient than longer ones, and
      an optimal loop of Henle distribution was found that is consistent with
      experimental findings.

PMID- 16967258
TI  - Proliferation and death in a binary environment: a stochastic model of cellular
      ecosystems.
AB  - The activation, growth and death of animal cells are accompanied by changes in
      the chemical composition of the surrounding environment. Cells and their
      microscopic environment constitute therefore a cellular ecosystem whose time
      evolution determines processes of interest for either biology (e.g. animal
      development) and medicine (e.g. tumor spreading, immune response). In this paper,
      we consider a general stochastic model of the interplay between cells and
      environmental cellular niches. Niches may be either favourable or unfavourable in
      sustaining cell activation, growth and death, the state of the niches depending
      on the state of the cells. Under the hypothesis of random coupling between the
      state of the environmental niche and the state of the cell, the rescaled model
      reduces to a set of four non-linear differential equations. The biological
      meaning of the model is studied and illustrated by fitting experimental data on
      the growth of multicellular tumor spheroids. A detailed analysis of the
      stochastic model, of its deterministic limit, and of normal fluctuations is
      provided.

PMID- 16967259
TI  - Stochastic kinetics description of a simple transcription model.
AB  - We study a stochastic model of transcription kinetics in order to characterize
      the distributions of transcriptional delay and of elongation rates.
      Transcriptional delay is the time which elapses between the binding of RNA
      polymerase to a promoter sequence and its dissociation from the DNA template
      strand with consequent release of the transcript. Transcription elongation is the
      process by which the RNA polymerase slides along the template strand. The model
      considers a DNA template strand with one promoter site and n nucleotide sites,
      and five types of reaction processes, which we think are key ones in
      transcription. The chemical master equation is a set of ordinary differential
      equations in 3(n) variables, where n is the number of bases in the template. This
      model is too huge to be handled if n is large. We manage to get a reduced Markov
      model which has only 2n independent variables and can well approximate the
      original dynamics. We obtain a number of analytical and numerical results for
      this model, including delay and transcript elongation rate distributions. Recent
      studies of single-RNA polymerase transcription by using optical-trapping
      techniques raise an issue of whether the elongation rates measured in a
      population are heterogeneous or not. Our model implies that in the cases studied,
      different RNA polymerase molecules move at different characteristic rates along
      the template strand. We also discuss the implications of this work for the
      mathematical modeling of genetic regulatory circuits.

PMID- 16967260
TI  - European Society of Gastrointestinal and Abdominal Radiology (ESGAR): consensus
      statement on CT colonography.
AB  - Rapid clinical dissemination of CT colonography (CTC) is occurring in parallel
      with continued research into technique optimisation and diagnostic performance. A
      need exists therefore for current guidance as to basic prerequisites for
      effective clinical implementation. A questionnaire detailing CTC technique,
      analysis, training and clinical implementation was developed by the European
      Society of Gastrointestinal and Abdominal Radiology (ESGAR) CTC committee and
      circulated to all faculty members of previous ESGAR "hands-on" CTC training
      courses. Responses were collated and a consensus statement produced. Of 27
      invited to participate, 24 responded. Reasonable consensus was reached on bowel
      preparation, colonic distension, patient positioning, use of IV contrast and
      optimal scan parameters. Both primary 2D and primary 3D analysis were advocated
      equally, with some evidence that more experienced readers prefer primary 2D.
      Training was universally recommended, although there was no consensus regarding
      minimum requirements. CTC was thought superior to barium enema, although
      recommended for screening only in the presence of validated local experience.
      There was consensus that polyps 4 mm or less could be ignored assuming agreement
      from local gastroenterological colleagues. There is increasing consensus amongst
      European experts as to the current best practice in CTC.

PMID- 16967262
TI  - Management of patients with epistaxis by general practitioners: impact of
      otolaryngology experience on their practice.
AB  - This study aims to assess the management of patients with epistaxis by general
      practitioners (GPs) and to show whether previous experience as a junior doctor in
      ear, nose and throat (ENT) surgery influences their practice. A questionnaire was
      sent together with self-addressed reply envelopes to a random sample of 1,000
      GPs. Four hundred and twenty eight GPs replied (43% response rate). Ninety-eight
      percent GPs see less than five epistaxis per week. Eighty-six percent GPs seek a
      specialist opinion for approximately one in four patients seen. Fifty percent GPs
      would arrange investigations. There was a wide variation in these and the first
      aid advice given. Fifteen percent GPs had previous experience in ENT. The only
      significant difference in the management of epistaxis with these GPs is that they
      were 2x more likely to cauterize a nose with silver nitrate (P=0.002). There is
      no general consensus on the management of epistaxis by GPs and despite previous
      experiences in the specialty as a junior doctor, this fails to have a significant
      impact on the day to day management of epistaxis.

PMID- 16967261
TI  - Gene expression and gene therapy imaging.
AB  - The fast growing field of molecular imaging has achieved major advances in
      imaging gene expression, an important element of gene therapy. Gene expression
      imaging is based on specific probes or contrast agents that allow either direct
      or indirect spatio-temporal evaluation of gene expression. Direct evaluation is
      possible with, for example, contrast agents that bind directly to a specific
      target (e.g., receptor). Indirect evaluation may be achieved by using specific
      substrate probes for a target enzyme. The use of marker genes, also called
      reporter genes, is an essential element of MI approaches for gene expression in
      gene therapy. The marker gene may not have a therapeutic role itself, but by
      coupling the marker gene to a therapeutic gene, expression of the marker gene
      reports on the expression of the therapeutic gene. Nuclear medicine and optical
      approaches are highly sensitive (detection of probes in the picomolar range),
      whereas MRI and ultrasound imaging are less sensitive and require amplification
      techniques and/or accumulation of contrast agents in enlarged contrast particles.
      Recently developed MI techniques are particularly relevant for gene therapy.
      Amongst these are the possibility to track gene therapy vectors such as stem
      cells, and the techniques that allow spatiotemporal control of gene expression by
      non-invasive heating (with MRI guided focused ultrasound) and the use of
      temperature sensitive promoters.

PMID- 16967263
TI  - New experimental model of sinus and cortical vein thrombosis in pigs for MR
      imaging studies.
AB  - INTRODUCTION: Diagnosis of cerebral sinus vein thrombosis is still a challenge
      for imaging. MRI and MRA play a major role in sinus imaging. For further
      development of MR techniques, MR-compatible animal models are required. The aim
      of this study was to develop an animal model for sinus thrombosis and additional
      cortical vein thrombosis with a clot of human blood for MR imaging studies.
      METHODS: A combined surgical and interventional approach was carried out in 13
      pigs. After minimal invasive surgical access to the anterior superior sagittal
      sinus and cortical vein, thrombosis with human blood was induced using an
      interventional catheter approach. MR imaging was performed prior to and after
      thrombus induction. RESULTS: Sinus thrombosis was induced in 12 of 13 animals.
      Three animals suffered acute subdural haemorrhage; one of these animals died
      during the intervention, and one died after thrombus induction. MR imaging of the
      thrombosed sinus could easily be performed without significant artefacts in 11 of
      13 animals. CONCLUSION: This new model of sinus and cortical vein thrombosis with
      a clot of human blood allows artefact-free imaging studies on MR.

PMID- 16967264
TI  - Ammonia removal from livestock wastewater by ammonia-assimilating microorganisms
      immobilized in polyvinyl alcohol.
AB  - We isolated ammonia-assimilating microorganisms from the livestock manure
      treatment systems and evaluated their ammonia-assimilating ability. Many isolates
      utilized ammonia at high rates when they were purely cultivated in a nitrogen
      limited medium to which sterilized lagoon extract had been added. Some isolates
      that were immobilized in polyvinyl alcohol (PVA) utilized ammonia present in the
      media containing viable lagoon microorganisms. Staining with 4',6'-diamidino-2
      phenylindole (DAPI) indicated that the immobilized high ammonia-assimilating
      isolates grew dominantly within the PVA beads. High ammonia-assimilating isolates
      in the mixed culture containing viable lagoon microorganisms were identified as
      Pseudomonas spp. and member of Rhizobiaceae species by partial sequencing of the
      16S ribosomal DNA.

PMID- 16967265
TI  - Production and characterization of thermostable alkaline phytase from Bacillus
      laevolacticus isolated from rhizosphere soil.
AB  - A novel phytase producing thermophilic strain of Bacillus laevolacticus
      insensitive to inorganic phosphate was isolated from the rhizosphere soil of
      leguminous plant methi (Medicago falacata). The culture conditions for production
      of phytase by B. laevolacticus under shake flask culture were optimized to obtain
      high levels of phytase (2.957 +/- 0.002 U/ml). The partially purified phytase
      from B. laevolacticus strain was optimally active at 70 degrees C and between pH
      7.0 and pH 8.0. The enzyme exhibited thermostability with approximately 80%
      activity at 70 degrees C and pH 8.0 for up to 3 h in the presence/absence of 5 mM
      CaCl(2). The phytase from B. laevolacticus showed high specificity for phytate
      salts of Ca(+) > Na(+). The enzyme showed an apparent K (m) 0.526 mM and V (max)
      12.3 mumole/min/mg of activity against sodium phytate.

PMID- 16967266
TI  - Immunohistochemical detection of bombesin receptor subtypes GRP-R and BRS-3 in
      human tumors using novel antipeptide antibodies.
AB  - Bombesin (BN)-like peptides can stimulate cancer cell growth through binding to
      their specific G protein-coupled receptors. It is well established that BN
      receptors are being overexpressed in a subset of human tumors; however, little is
      known about the cellular and subcellular localization of individual BN receptor
      subtypes in these tissues. In this study, we developed and characterized novel
      antipeptide antibodies to the carboxy terminal regions of the gastrin-releasing
      peptide-preferring bombesin receptor (GRP-R) and the bombesin receptor subtype-3
      (BRS-3). Specificity of the antisera was demonstrated by (1) detection of broad
      bands migrating at Mr 50,000-70,000 in Western blots of membranes from receptor
      expressing tissues; (2) cell surface staining of transfected cells; (3)
      translocation of GRP-R receptor immunostaining after BN exposure; and (4)
      abolition of tissue immunostaining by preadsorbtion of the antibodies with their
      immunizing peptides. The distribution of BN receptors was investigated in 74
      formalin-fixed, paraffin-embedded human tumors. GRP-R receptors were most
      frequently detected in breast and prostate carcinomas. BRS-3 receptors were often
      detected in prostate and pancreatic carcinomas and in pituitary adenomas.
      Immunoreactive GRP-R and BRS-3 receptors were in many cases predominantly
      confined to the plasma membrane and uniformly present on nearly all tumor cells.
      The development of these novel antipeptide antibodies will facilitate the
      identification of those tumors, which may be targets for diagnostic or
      radiotherapeutic application of subtype-selective BN analogs.

PMID- 16967267
TI  - TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a
      grading system.
AB  - The need for standards in the management of patients with endocrine tumors of the
      digestive system prompted the European Neuroendocrine Tumor Society (ENETS) to
      organize a first Consensus Conference, which was held in Frascati (Rome) and was
      based on the recently published ENETS guidelines on the diagnosis and treatment
      of digestive neuroendocrine tumors (NET). Here, we report the tumor-node
      metastasis proposal for foregut NETs of the stomach, duodenum, and pancreas that
      was designed, discussed, and consensually approved at this conference. In
      addition, we report the proposal for a working formulation for the grading of
      digestive NETs based on mitotic count and Ki-67 index. This proposal, which needs
      to be validated, is meant to help clinicians in the stratification, treatment,
      and follow-up of patients.

PMID- 16967268
TI  - MRI of traumatic patellar dislocation in children.
AB  - BACKGROUND: Traumatic patellar dislocations (TPD) are common injuries in
      children, and MRI is useful in evaluation of pediatric musculoskeletal injuries.
      However, no pediatric studies on the MR features of TPD have been reported.
      OBJECTIVE: To review the injuries after TPD in children. MATERIALS AND METHODS:
      Patients with clinical or radiological recognition of TPD and those with
      suggestive MR findings were selected. Bone, cartilage and soft-tissue injuries
      and patellofemoral relationships were assessed. RESULTS: A total of 26 patients
      (age range 10-18 years) were identified. The following injuries were seen: bone
      bruising of the inferomedial patella (81% of patients) and the lateral femoral
      condyle (81% of patients), cartilage injuries of the inferomedial patella (38% of
      patients) and the lateral femoral condyle (38% of patients), osteochondral
      fragments (42% of patients) and injuries of the medial patellar restraints (81%
      of patients). CONCLUSION: Pediatric manifestations of TPD seen on MRI are similar
      to those in adults. TPD is often occult in children. Early recognition of bone
      bruising of the patella and lateral femoral condyle, associated osteochondral
      injuries, and medial patellar stabilizer injury is important for timely
      diagnosis.

PMID- 16967269
TI  - Neonatal nasal obstruction caused by bilateral dacryocystoceles.

PMID- 16967270
TI  - Tracheoesophageal fistula without esophageal atresia: are pull-back tube
      esophagograms needed for diagnosis?
AB  - BACKGROUND: A pull-back tube esophagogram (PBTE) is widely accepted in the
      literature as the radiological investigation of choice for the diagnosis of
      tracheoesophageal fistula without esophageal atresia. However, PBTE is rarely
      performed in our institution, as we have been successful in confirming the
      presence of such fistulae with a contrast material swallow (CS). We hypothesized
      that PBTE is not the radiological investigation of choice for the diagnosis of
      the fistula in this condition. OBJECTIVE: We sought to determine what proportion
      of patients with tracheoesophageal fistula without esophageal atresia can be
      diagnosed promptly by a CS and what the indications are for a PBTE. MATERIALS AND
      METHODS: We retrospectively analyzed the clinical and radiological findings in
      patients with tracheoesophageal fistula without esophageal atresia to determine
      whether the fistula was diagnosed with a CS or PBTE. RESULTS: We identified 20
      children (13 female and 7 male) with tracheoesophageal fistula without esophageal
      atresia. Their age at diagnosis ranged from 3 days to 168 months with a median of
      9 days. The diagnosis was documented by CS in 12, PBTE in 7 and CT in 1. In three
      of the seven who had the fistula documented by PBTE, a previous CS had shown
      contrast material in the trachea, but no fistulous tract or aspiration was
      identified. CONCLUSION: We believe that CS should be the examination of choice in
      most patients suspected of having a tracheoesophageal fistula without esophageal
      atresia. A PBTE is indicated in patients who are intubated or are at significant
      risk of aspiration. Furthermore, a PBTE is also indicated where contrast material
      is seen in the airway on CS and there is uncertainty whether this is due to
      aspiration or a fistula.

PMID- 16967271
TI  - Highly predictable photosynthetic production in natural macroalgal communities
      from incoming and absorbed light.
AB  - Photosynthesis-irradiance relationships of macroalgal communities and thalli of
      dominant species in shallow coastal Danish waters were measured over a full year
      to test how well community production can be predicted from environmental
      (incident irradiance and temperature) and community variables (canopy
      absorptance, species number and thallus metabolism). Detached thalli of dominant
      species performed optimally at different times of the year, but showed no general
      seasonal changes in photosynthetic features. Production capacity of communities
      at high light varied only 1.8-fold over the year and was unrelated to incident
      irradiance, temperature and mean thallus photosynthesis, while community
      absorptance was a highly significant predictor. Actual rates of community
      photosynthesis were closely related to incident and absorbed irradiance alone.
      Community absorptance in turn was correlated to canopy height and species
      richness. The close relationship of community photosynthesis to irradiance is due
      to the fact that (1) large differences in thallus photosynthesis of individual
      species are averaged out in communities composed of several species, (2) seasonal
      replacement of species keeps communities metabolically active, and (3) maximum
      possible absorptance at 100% constrains the total photosynthesis of all species.
      Our results imply that the photosynthetic production of macroalgal communities is
      more predictable than their complex and dynamic nature suggest and that
      predictions are possible over wide spatial scales in coastal waters by
      measurements of vegetation cover, incoming irradiance and canopy absorptance.

PMID- 16967272
TI  - Correlation of metabolism with tissue carbon and nitrogen turnover rate in small
      mammals.
AB  - Stable isotopes have proven to be a useful tool for deciphering food webs,
      examining migration patterns and determining nutrient resource allocation. In
      order to increase the descriptive power of isotopes, an increasing number of
      studies are using them to model tissue turnover. However, these studies have,
      mostly by necessity, been largely limited to laboratory experiments and the
      demand for an easier method of estimating tissue turnover in the field for a
      large variety of organisms remains. In this study, we have determined the
      turnover rate of blood in mice and rats using stable isotope analysis, and
      compared these rates to the metabolic rates of the animals. Rats (Rattus
      norvegicus) (n=4) and mice (Mus musculus) (n=4) were switched between
      isotopically distinct diets, and the rate of change of delta(13)C and delta(15)N
      in whole blood was determined. Basal metabolic rates (as CO(2) output and O(2)
      consumption per unit time, normalized for mass) were determined for the rats and
      mice. Rats, which were an order of magnitude larger and had a slower metabolic
      rate per unit mass than mice (0.02 vs. 0.14 O(2)/min/g), had a slower blood
      turnover than mice for (13)C (t (1/2 )=24.8 and 17.3 days, respectively) and
      (15)N (t (1/2 )=27.7 and 15.4 days, respectively). A positive correlation between
      metabolic rate and blood isotopic turnover rate was found. These are the only
      such data for mammals available, but the literature for birds shows that mass and
      whole-body metabolic rates in birds scale logarithmically with tissue turnover.
      Interestingly, the mammalian data graph separately from the bird data on a
      turnover versus metabolic rate plot. Both mice and rat tissue in this study
      exhibited a slower turnover rate compared to metabolic rate than for birds. These
      data suggest that metabolic rate may be used to estimate tissue turnover rate
      when working with organisms in the field, but that a different relationship
      between tissue turnover and metabolism may exist for different classes of
      organisms.

PMID- 16967273
TI  - Fasting plasma glucose as a screening test for gestational diabetes mellitus.
AB  - Although debated, most preeminent expert panels recommend routine screening for
      gestational diabetes mellitus (GDM). Among the many tests that have been used and
      evaluated for the screening of GDM, the fasting plasma glucose (FPG) remains very
      appealing. It is easy to administer, well tolerated, inexpensive, reproducible
      and patient friendly. However attractive, the FPG has given varied results in
      different populations and its use as a screening test for GDM remains uncertain.
      This review will objectively assess the available studies to find the real value
      of FPG as a screening test for GDM.

PMID- 16967274
TI  - Vaginal fluid urea and creatinine in diagnosis of premature rupture of membranes.
AB  - OBJECTIVE: To evaluate the reliability of vaginal fluid urea and creatinine for
      the diagnosis of premature rupture of membranes (PROMs). MATERIALS AND METHODS: A
      total of 139 pregnant women were recruited. Group I consisted of 47 patients with
      diagnosis of PROM confirmed by amniotic fluid pooling and nitrazine paper test.
      Group II consisted of 36 patients in whom diagnosis of PROM was suspected but
      unconfirmed by amniotic fluid pooling (+/-) and/or nitrazine paper test (+/-).
      Group III consisted of 56 pregnant women without any complaint or complication.
      All patients underwent speculum examination for amniotic fluid pooling, nitrazine
      paper test, vaginal washing fluid urea and creatinine sampling. One-way ANOVA
      test, Scheffe multiple comparison test and receiver operating characteristic
      curve analysis were used. RESULTS: The mean vaginal fluid urea levels in group I,
      II, and III were 34.6 +/- 5.3, 2.4 +/- 5.3 and 1.3 +/- 6.2 mg/dl, respectively,
      where the difference was statistically significant (P < 0.001). The mean vaginal
      fluid creatinine concentrations of group I were, 1.5 +/- 0.3 mg/dl, found higher
      against the group II, 0.34 +/- 0.22 mg/dl, and group III, 0.28 +/- 0.23 mg/dl (P
      < 0.01). The sensitivity, specificity, positive predictivity, and negative
      predictivity were all 100% in detecting PROM by evaluation of vaginal fluid urea
      and creatinine concentration with a cut-off value of 12 and 0.6 mg/dl,
      respectively. CONCLUSION: Vaginal washing fluid urea and creatinine determination
      for the diagnosis of PROM is a reliable, simple and rapid test.

PMID- 16967275
TI  - Bilateral encapsulated adipocytic prosoplasia of ovary with fat necrosis: a case
      report.
AB  - Mature adipose tissue is not a normal component of ovarian cortical stroma.
      Rarely, it is seen as a phenomenon termed adipocytic prosoplasia of ovarian
      stroma, which occurs as an unencapsulated collection of mature adipocytes. The
      lesions in differential diagnosis of adipocytic prosoplasia can range from
      reactive/benign to aggressive conditions. The exact diagnosis of this entity is
      essential, since no further intervention is required. We describe a case of a 45
      year-old female presenting with uterine leiomyomata. Bilateral ovaries were
      normal on gross inspection. Microscopy of both ovaries showed circumscribed
      encapsulated subcapsular foci of adipose tissue with focal necrosis and
      calcification, suggestive of fat necrosis. No teratomatous elements were found on
      multiple sections examined, and a diagnosis of bilateral adipocytic prosoplasia
      with fat necrosis was considered. We report this case due to its intriguing and
      interesting finding, with an emphasis on the various differential diagnoses to be
      considered in such a case. Extensive examination, special stains and clinico
      pathological correlation help in arriving at a proper diagnosis. Our case is the
      first report of an ovarian adipocytic prosoplasia with fat necrosis.

PMID- 16967276
TI  - Effect of prepregnancy body mass index categories on obstetrical and neonatal
      outcomes.
AB  - OBJECTIVES: To examine the association between body mass index (BMI) and
      obstetrical and neonatal outcomes. METHODS: We conducted a cohort study comparing
      prepregnant BMI categories with obstetrical and neonatal outcomes using the
      McGill Obstetrical and Neonatal Database on all deliveries in 10 year period
      (1987-1997). Prepregnant BMI was categorized into underweight (<20), normal (20
      24.9), overweight (25-29.9), obese (30-39.9), and morbidly obese (40+). Logistic
      regression analysis was used to adjust for age, smoking, parity, and preexisting
      diabetes using normal BMI as the reference. RESULTS: The population consisted of
      underweight 4,312 (23.1%), normal weight 10,021 (53.8%), overweight 3,069
      (16.5%), obese 1,137 (6.1%), and morbidly obese 104 (0.6%). As compared to women
      with normal BMIs, overweight, obese, and morbidly obese women had an increased
      risk of preeclampsia 2.28 (1.88-2.77), 4.65 (3.71-5.83), 6.26 (3.48-11.26);
      gestational hypertension 1.56 (1.35-1.81), 2.01 (1.64-2.45), 2.77 (1.60-4.78);
      gestational diabetes 1.89 (1.63-2.19), 3.22 (2.68-3.87), 4.71 (2.89-7.67);
      preterm birth 1.20 (1.04-1.38), 1.60 (1.32-1.94), 2.43 (1.46-4.05); cesarean
      section 1.48 (1.35-1.62), 1.85 (1.62-2.11), 2.92 (1.97-4.34); and macrosomia 1.66
      (1.23-2.24), 2.32 (1.58-3.41), 2.10 (0.64-6.86). Underweight women were less
      likely to have: preeclampsia 0.67 (0.52-0.86), gestational hypertension 0.71
      (0.60-0.83), gestational diabetes 0.82 (0.69-0.97), cesarean section 0.89 (0.81
      0.97), shoulder dystocia 0.88 (0.80-0.96), birth injuries 0.40 (0.21-0.77), and
      macrosomia 0.43 (0.28-0.68) but more likely to have small for gestational age
      infants 1.54 (1.37-1.72) and intrauterine growth restricted infants 1.33 (1.07
      1.67). CONCLUSION: In a large Canadian teaching hospital, increasing prepregnancy
      BMI category was associated with an increasing risk of adverse pregnancy
      outcomes. Underweight prepregnancy BMI was associated with a reduced risk of
      adverse pregnancy outcomes.

PMID- 16967277
TI  - Observer reliability in evaluating pedicle screw placement using computed
      tomography.
AB  - Pedicle screw insertion in spinal surgery is a demanding technique with potential
      risks to neurological structures, for example, within the spinal canal. Assessing
      screw placement in clinical practice has been performed using plain radiographs
      and/or mainly axial computed tomography (CT) images. Screw placement using CT
      image reconstructions in multiple planes has been described, but its reliability
      has yet to be studied. This study aimed at addressing the clinical issue of
      interobserver and intraobserver reliability in the use of axial and coronal CT
      images for the assessment of pedicle screw placement. Fifty nine pedicle screws
      were studied by two experienced radiologists on two separate occasions. Screw
      placement was classified as "in", "out" or "questionable". On average, 88% and
      92% of the screws were classified as "in" by the first and second radiologist,
      respectively. Intraobserver agreement strength was almost perfect for both
      observers using either axial or coronal images. Interobserver agreement strength
      was almost perfect (axial) and substantial (coronal) in the first reading and
      substantial (axial, coronal) in the second reading. Assessing screw placement in
      more than one CT imaging plane is not only useful but reliable. Routine use may
      enhance reporting quality of screw placement by surgeons and radiologists.

PMID- 16967278
TI  - Lumbar hyperlordosis of neuromuscular origin: pathophysiology and surgical
      strategy for correction.
AB  - Lumbar hyperlordosis of neuromuscular origin is rare and requires surgical
      treatment in order to preserve a good sitting posture. We report twenty-seven
      cases of a preponderantly sagittal hyperlordosis deformity of the lumbar spine in
      patients with neuromuscular disorders and identify the indications and results of
      treatment. Seventeen males and ten females, aged 13 to 27 years, underwent
      operations for a lumbar hyperlordosis of neuromuscular origin responsible for
      major difficulties in sitting. In all patients, the sacrum was horizontal and
      associated in twenty-six cases with marked pelvic anteversion. Eleven patients
      were treated surgically by a posterior approach. The sixteen remaining patients
      had a preliminary discectomy, followed by posterior correction and fusion. Lumbar
      hyperlordosis was reduced from 8 degrees to 77 degrees between L1 and S1. The
      horizontal sacrum was partially reduced with an improvement from 8 degrees to 50
      degrees . Consequently, patients recovered a comfortable sitting position. One
      patient died of respiratory complications six weeks after surgery. Surgical
      correction is a demanding procedure which can be performed by a posterior
      approach. It is mandatory to analyse the spino-pelvic balance to avoid iliac
      retroversion and the loss of the role of the ischia in the sitting position.

PMID- 16967279
TI  - Megaprostheses for the treatment of malignant bone tumours of the lower limbs.
AB  - Lower limb salvage surgery remains a challenge in orthopaedic oncology. Both
      cemented and cementless, modular, endoprosthetic systems are widely used to treat
      defects of different sizes. The systems have changed over the years, and each
      major orthopaedic company offers a modular tumour and revision system for the
      lower extremities. All systems have worse long-term results compared to
      conventional total hip or total knee systems. This is due to the large defects
      that need to be bridged with a more difficult fixation in the diapyhsis of the
      femur and tibia and a more complex restoration of joint biomechanics. This
      article summarises the results of several clinical studies with different
      systems. Newer systems without clinical follow-up are described. We previously
      reported a prospective study of 50 consecutive patients treated with the MUTARS
      endoprostheses. The follow-up was 2-7 years. Clinical evaluation showed good
      results compared to other systems. The review of the literature and our own
      results do not validate the support or favouring of one specific system. The
      surgeon should choose a system with which he/she is familiar and that provides
      the modularity needed intraoperatively to bridge any defect in the lower limbs.

PMID- 16967280
TI  - Tumor specific phage particles promote tumor regression in a mouse melanoma
      model.
AB  - Within cancer research, phage display libraries have been widely used for the
      identification of tumor targeting peptides and antibodies. Additionally, phages
      are known to be highly immunogenic; therefore we evaluated the immunotherapeutic
      potential of tumor specific phages to treat established solid tumors in a mouse
      model of melanoma. We developed two tumor specific phages, one derived from a
      peptide phage display library and one Fab expressing phage with known
      specificity, for the treatment of mice bearing palpable B16-F10 or B16/A2K(b)
      tumors. Therapy in B16-F10 tumor bearing mice with tumor specific phages was
      superior to treatment with non-tumor specific phages and lead to delayed tumor
      growth and increased survival. In B16/A2K(b )tumor bearing mice, therapy with
      tumor specific phages resulted in complete tumor regression and long-term
      survival in 50% of the mice. Histological analysis of tumors undergoing treatment
      with tumor specific phages revealed that phage administration induced a massive
      infiltration of polymorphonuclear neutrophils. Furthermore, phages induced
      secretion of IL-12 (p70) and IFN-gamma as measured in mouse splenocyte culture
      supernatants. These results demonstrate a novel, immunotherapeutic cancer
      treatment showing that tumor specific phages can promote regression of
      established tumors by recruitment of inflammatory cells and induction of Th1
      cytokines.

PMID- 16967281
TI  - Mitochondrial DNA deletion in a girl with Fanconi's syndrome.
AB  - We report a sporadic large-scale mitochondrial deletion in a paediatric patient
      with Fanconi's syndrome. Renal biopsy disclosed chronic interstitial nephritis.
      Ultrastructural examination of the renal tissue showed many giant atypical
      mitochondria. Histochemical stains revealed markedly reduced cytochrome c oxidase
      (COX). Genetic analysis disclosed a novel mitochondrial deletion of 7.3 kb in
      both peripheral blood and renal tissue. Mitochondrial diseases have heterogeneous
      clinical phenotypes; mutation analysis has proved to be an effective tool in
      confirming the diagnosis.

PMID- 16967282
TI  - Mild hydronephrosis in newborns and infants: can ultrasound predict the presence
      of vesicoureteral reflux.
AB  - The objective of our study was to determine the significance of mild
      hydronephrosis in newborns and infants as an indicator of vesicoureteral reflux
      (VUR). The voiding cystourethrography (VCUG) of 573 patients aged 0-18 months
      with mild, sonographically detected hydronephrosis were reviewed for VUR.
      Patients with secondary reflux or anomalies making an exact reflux grading
      impossible were excluded. Normal kidneys, contralateral to hydronephrotic ones,
      were included. Each kidney was considered separately, forming a total of 1,146
      renal units. Mild hydronephrosis was defined as an anteroposterior diameter of
      the renal pelvis of 0.5-1.5 cm without caliectasis. The International Grading
      System was used to grade VUR. Seven hundred and thirty-six kidneys had mild
      hydronephrosis. VUR occurred in 189 out of 736 (25.7%) of these kidneys, and in
      108 out of 410 (26.3%) non-distended kidneys, contralateral to hydronephrotic
      ones (p=0.806). No statistical differences in the frequency of VUR and dilatation
      were found between the subgroups of patients with and without infection, except
      for a higher grade of reflux in the group with infection. The frequency of VUR in
      mildly dilated kidneys was not significantly different from that in non-distended
      ones. There was a poor correlation between VUR and mild hydronephrosis. The
      latter should not be considered in itself an indication for VCUG in asymptomatic
      neonates and infants.

PMID- 16967283
TI  - Prognostic significance of microalbuminuria in postdiarrheal hemolytic uremic
      syndrome.
AB  - Patients who survive the acute phase of postdiarrheal hemolytic uremic syndrome
      (D+ HUS) may develop renal complications after years of apparent recovery. The
      optimal regimen for monitoring these children is unclear. We therefore determined
      if screening for microalbuminuria, in the absence of overt proteinuria at follow
      up, increased the sensitivity for predicting long-term renal-related sequelae. We
      found that screening for microalbuminurea, within the first 6-18 months following
      an episode of HUS, increased the sensitivity for predicting later sequelae from
      22 to 66.7%, compared to screening for overt proteinuria alone. These findings,
      if confirmed by a larger cohort with more years of follow-up, may facilitate
      early initiation of intervention strategies designed to reduce progressive renal
      damage.

PMID- 16967284
TI  - Maternal diabetes mellitus--early consequences for the offspring.
AB  - Although several studies have focused on the effects of nutritional status during
      intrauterine development, few have addressed the impact of maternal diabetes
      mellitus on renal function and morphology in the young offspring. In the present
      study, renal morpho-functional aspects were studied in the offspring of diabetic
      rats. Diabetes was induced in female rats with a single dose of streptozotocyn
      (STZ), 10 days before mating. After weaning, the offspring (DO) had free access
      to food and water. Arterial blood pressure was measured, by tail plethysmography,
      from 2 months on. Renal function was evaluated in 2- and 3-month-old rats in the
      DO group and in controls (C). Analysis of renal morphology was carried out in
      newborn and in 1-, 2- and 3-month-old rats in both groups. Although the nephron
      number was not changed in the DO group, glomerular hypertrophy was observed from
      2 months on. At the same age, the glomerular filtration rate was significantly
      reduced in DO, and blood pressure was significantly increased, when compared to
      C. Glucose tolerance test (GTT) from DO showed a different profile when compared
      to C. The number of PCNA positive cells in renal tissue was similar in both
      groups. Our data suggests that exposure to intrauterine diabetes may be an
      important cause of both impaired renal function and hypertension in offspring,
      without changes in the nephron number.

PMID- 16967285
TI  - Voiding dysfunction in children. Pelvic-floor exercises or biofeedback therapy: a
      randomized study.
AB  - Fifty-six patients 5.9-15.2 years old with dysfunctional elimination syndrome
      (DES) unimproved by previous therapies were randomly distributed into two voiding
      training programs: group 1 contained 26 patients submitted to 24 training
      sessions over a 3-month period; group 2 contained 30 patients submitted to 16
      sessions over a 2-month period. Both groups adhered to a voiding and drinking
      schedule, received instruction on adequate toilet posture, were reinforced
      through the maintenance of voiding diaries, and went through proprioceptive and
      pelvic floor muscle training (Kegel exercises). Group 2 patients also received
      biofeedback therapy. Clinical evaluation was carried out before each program's
      initiation and 1, 6, and 12 months after each program's termination. All patients
      were submitted to renal ultrasonography and dynamic ultrasonography before and 6
      months after each program's conclusion. Millivoltage recordings of pelvic floor
      muscles were compared before and after training. Urinary continence was improved
      after completion of either training program. Only those patients who received
      biofeedback training showed a significant decrease in postvoiding residual (PVR)
      urine as detected by dynamic ultrasonography. Our results show that either
      training regime can reduce episodic urinary incontinence and urinary tract
      infection but that further study is required to identify the optimal training
      duration.

PMID- 16967286
TI  - Steroid-resistant nephrotic syndrome: the influence of race on cyclophosphamide
      sensitivity.
AB  - Steroid-resistant (SR) forms of nephrotic syndrome (NS) have a poorer outcome in
      blacks compared to other racial groups. In this study, 223 children with SRNS,
      aged 1-16 years old, were analysed retrospectively for the period 1976-2004.
      Treatment schedules included oral cyclophosphamide (2-3 mg/kg) with prednisone
      0.5-1 mg/kg (maximum 60 mg) only (n=90); prednisone on alternate days with
      methylprednisolone (30 mg/kg, maximum 1 g) and oral cyclophosphamide (n=117);
      oral prednisone on alternate days, three doses of intravenous methylprednisolone
      on alternate days and monthly doses of intravenous cyclophosphamide (500-750 mg
      m(-2) dose(-1)x7 doses monthly) (n=10); or cyclosporine 5 mg kg(-1) day(-1)
      adjusted to a trough level of 150-200 mg/ml (n=6). We compared the clinical and
      biochemical characteristics and outcome using different forms of therapies. A
      total of 183 (82.1%) underwent biopsy; 84 (45.9%) were Indian and 99 (54.1%) were
      black. Sixty-six (36.1%) had minimal change NS, 66 (36.1%) had focal segmental
      glomerulosclerosis (FSGS), 15 (8.2%) had a proliferative form of NS, and 36
      (19.7%) had other forms of NS. Of the 84 Indian children biopsied, 58 (69.0%)
      were in complete remission, including 29 of 40 (72.5%) treated with oral
      cyclophosphamide and prednisone only. Of the 99 black children who were biopsied,
      20 (20.2%) achieved complete remission; none of those treated with oral
      cyclophosphamide and prednisone only achieved complete remission. Of the 40
      Indian children who were not biopsied who received only oral prednisone and
      cyclophosphamide, 32 (80%) achieved complete remission. This study shows Indian
      children with SRNS respond better to treatment than black children (69.0 vs.
      20.2%). Since 80% of Indian children with SRNS responded to a trial of oral
      cyclophosphamide and prednisone, we propose the use of oral cyclophosphamide
      therapy in non-black children before embarking on renal biopsy.

PMID- 16967287
TI  - Idiopathic nephrotic syndrome in Polish children - its variants and associations
      with HLA.
AB  - HLA-DR and HLA-DQ antigens were investigated in 127 Polish children with
      idiopathic nephrotic syndrome (INS) followed-up for the median time of 11 years
      (minimum 7 years). HLA typing was performed using the polymerase chain reaction
      sequence-specific oligonucleotide probing technique and the
      microlymphocytotoxicity test. Histopathologic INS categories and a response to
      therapy were analyzed according to particular HLA associations. The results were
      compared with 330 healthy individuals. In INS children, we observed an increased
      frequency of HLA-DR7, DR3/7, DQ2 and DQ8, whereas HLA-DR13, DR15, DQ5 and DQ6
      were decreased. In minimal change nephrotic syndrome, a relationship with HLA
      DR3, DR7, DR3/7 and DQ2 was found. Evolved from minimal changes, focal segmental
      glomerulosclerosis was associated with HLA-DR7, while primary focal segmental
      glomerulosclerosis with HLA-DR4 and DQ8. In steroid-dependence and secondary
      steroid-resistance, an increased frequency of HLA-DR3, DR7, DR3/7 and DQ2 was
      documented. In contrast, primary steroid-resistant nephrotic syndrome was
      associated with HLA-DR4 and DQ8. Steroid-dependent patients bearing HLA-DR3
      achieved longer remissions after chlorambucil therapy compared with HLA-DR3
      negative. In steroid-resistant focal segmental glomerulosclerosis, a reduced
      response to cyclosporine A was associated with HLA-DR4. Associations with HLA
      differentiate between pathoanatomic entities of INS and may influence a response
      to immunosuppressive therapy.

PMID- 16967288
TI  - Symptomatic resolution of spinal osteoid osteoma with conservative management:
      imaging correlation.
AB  - A 10-year-old girl presented with a history of painful scoliosis. Imaging
      performed, including computed tomography (CT) and magnetic resonance imaging
      (MRI), demonstrated a lesion with radiological features consistent with an
      osteoid osteoma (OO) of the 6th thoracic vertebra. The patient was treated
      conservatively with non-steroidal anti-inflammatory drugs (NSAIDs). Over eight
      months of clinical and radiological surveillance, she became entirely
      asymptomatic and demonstrated complete resolution of the scoliotic curve. The CT
      and MRI features of the osteoid osteoma during the period of surveillance are
      presented and are correlated with the corresponding clinical features.

PMID- 16967289
TI  - Congenital pseudoarthrosis associated with venous malformation.
AB  - Congenital pseudoarthrosis is a pathologic entity that may be isolated, or may be
      associated with neurofibromatosis. We report the case of a 3-year-old female with
      congenital pseudoarthrosis involving the right tibia and fibula. Magnetic
      resonance imaging (MRI) and complementary magnetic resonance angiogram (MRA)
      revealed a lobulated mass with vivid enhancement, which led to the diagnosis of
      venous malformation. This is the first report of congenital pseudoarthrosis
      caused by the presence of a vascular malformation.

PMID- 16967290
TI  - Adaptive feature extraction for EEG signal classification.
AB  - One challenge in the current research of brain-computer interfaces (BCIs) is how
      to classify time-varying electroencephalographic (EEG) signals as accurately as
      possible. In this paper, we address this problem from the aspect of updating
      feature extractors and propose an adaptive feature extractor, namely adaptive
      common spatial patterns (ACSP). Through the weighed update of signal covariances,
      the most discriminative features related to the current brain states are
      extracted by the method of multi-class common spatial patterns (CSP). Pseudo
      online simulations of EEG signal classification with a support vector machine
      (SVM) classifier for multi-class mental imagery tasks show the effectiveness of
      the proposed adaptive feature extractor.

PMID- 16967291
TI  - Reanalysis of constitutively active rat and human 5-HT7(a) receptors in HEK-293F
      cells demonstrates lack of silent properties for reported neutral antagonists.
AB  - The present study reinvestigated a series of 5-HT receptor antagonists at both
      constitutively active rat and human 5-HT7(a) receptors in HEK-293F cells using
      the cAMP signalling pathway as a functional read-out. Both rat and human 5-HT7(a)
      receptors were expressed in similar amounts ([3H]-LSD binding: 1.0 to 1.1 pmol/mg
      protein). Attenuation of basal cAMP formation by the inverse agonist SB-691673 (1
      microM) was slightly larger by the human 5-HT7(a) (-73+/-3 %) than rat 5-HT7(a)
      receptor (-62+/-3 %). The 5-HT receptor antagonists investigated here displayed
      systematically inverse agonism. While methiothepin and SB-269970 displayed
      similar negative intrinsic activity to SB-691673 at the rat 5-HT7(a) receptor,
      the compounds SB-258719, mesulergine and metergoline displayed some lower
      negative intrinsic activity (between -38 and -49%). Inverse agonist properties
      were observed with potencies fitting with their respective binding pIC50 values
      and pKB values as estimated from antagonist studies with 5-HT. With the exception
      of SB-258719 and mesulergine, which remained a partial inverse agonist at the
      human 5-HT7(a) receptor, the other compounds behaved with a similar Emax value to
      the full inverse agonist SB-691673. In conclusion, none of the 5-HT receptor
      antagonists investigated displayed silent properties at the rat or human 5-HT7(a)
      receptor, when these are expressed in a system allowing detection of constitutive
      activity. They appear to be partial to full inverse agonists, further
      illustrating that an antagonist is preferentially an inverse agonist when
      investigated under constitutively active receptor conditions.

PMID- 16967292
TI  - Generation and maintenance of human memory cells during viral infection.
AB  - Long-term maintenance of memory T cell response is the hallmark of immune
      protection and hence the holy grail of most vaccine development studies.
      Persistent memory cells, developed after either viral infection or vaccination,
      ensure the generation of an antiviral response upon reexposure to the pathogen.
      During acute viral infections, as in the case of measles and influenza viruses,
      strong T cell effector functions, which eradicate the virus and protect patients
      against reexposure, are achieved by the generation of persistent protective
      memory cells. However, in chronic infections, T cells drastically lose effector
      functions before acquiring a memory phenotype. Chronic infections can be
      categorized into infections where viremia is controlled and protective memory
      cells are maintained as in the case of EBV and CMV infections, or where the virus
      persists and memory cells are exhausted and disrupted as in the case of human
      immunodeficiency virus infection. In this review, we will discuss the different
      phenotypical and functional characteristics of memory cells subsets, the
      importance of the role they play during acute and chronic infections, and the
      mechanisms behind their effectiveness and persistence.

PMID- 16967293
TI  - Mechanisms of lineage segregation in the avian dermomyotome.
AB  - The somite and its intermediate derivatives, sclerotome and dermomyotome (DM),
      are composed of distinct subdomains based on lineage analysis and gene expression
      patterns. This sets the grounds for elucidating the mechanisms underlying
      differential cell specification and morphogenesis. By examining the in vivo roles
      of N-cadherin on discrete domains of the somitic epithelium at various times, our
      recent studies highlight the existence of a regional and temporal heterogeneity
      in cellular responsiveness. As examples of this assortment, we document a
      coupling between asymmetric cell division and fate segregation in the DM sheet,
      sequential effects of N-cadherin-mediated adhesion on early myogenic
      specification compared to later myofiber patterning, and a differential behavior
      of pioneer myoblasts compared to later myogenic waves.

PMID- 16967294
TI  - Results from the International Conference of Experts on Intra-abdominal
      Hypertension and Abdominal Compartment Syndrome. I. Definitions.
AB  - OBJECTIVE: Intra-abdominal hypertension (IAH) and abdominal compartment syndrome
      (ACS) have been increasingly recognized in the critically ill over the past
      decade. The variety of definitions proposed has led to confusion and difficulty
      in comparing one study to another. DESIGN: An international consensus group of
      critical care specialists convened at the second World Congress on Abdominal
      Compartment Syndrome to standardize definitions for IAH and ACS based upon the
      current understanding of the pathophysiology surrounding these two syndromes.
      METHODS: Prior to the conference the authors developed a blueprint for the
      various definitions, which was further refined both during and after the
      conference. The present article serves as the final report of the 2004
      International ACS Consensus Definitions Conference and is endorsed by the World
      Society of Abdominal Compartment Syndrome (WSACS). RESULTS: IAH is redefined as
      an intra-abdominal pressure (IAP) at or above 12 mmHg. ACS is redefined as an IAP
      above 20 mmHg with evidence of organ dysfunction/failure. ACS is further
      classified as either primary, secondary, or recurrent based upon the duration and
      cause of the IAH-induced organ failure. Standards for IAP monitoring are set
      forth to facilitate accuracy of IAP measurements from patient to patient.
      CONCLUSIONS: State-of-the-art definitions for IAH and ACS are proposed based upon
      current medical evidence as well as expert opinion. The WSACS recommends that
      these definitions be used for future clinical and basic science research.
      Specific guidelines and recommendations for clinical management of patients with
      IAH/ACS are published in a separate review.

PMID- 16967296
TI  - Acute otitis media and respiratory viruses.
AB  - The present study was performed to elucidate the clinical outcome, and etiology
      of acute otitis media (AOM) in children based on virologic and bacteriologic
      tests. The study group consisted of 120 children aged 6 to 144 months with AOM.
      Middle ear fluid (MEF) was tested for viral pathogens by reverse transcriptase
      polymerase chain reaction (RT-PCR) and for bacteria by gram-staining and culture.
      Clinical response was assessed on day 2 to 4, 11 to 13, 26 to 28. Respiratory
      viruses were isolated in 39 patients (32.5%). Respiratory syncytial virus (RSV)
      (46.5%) was the most common virus identified in MEF samples, followed by human
      rhinovirus (HRV) (25.6%), human coronavirus (HCV) (11.6%), influenza (IV) type A
      (9.3%), adenovirus type sub type A (AV) (4%), and parainfluenza (PIV) type -3
      (2%) by RT-PCR. In total 69 bacterial species were isolated from 65 (54.8%) of
      120 patients. Streptococcus pneumoniae (S. pneumoniae) was the most frequently
      isolated bacteria. Viral RNA was detected in 31 (56.3%) of 55 bacteria-negative
      specimens and in 8 (12.3%) of 65 bacteria-positive MEF samples. No significant
      differences were found between children representing viral infection alone,
      combined viral and bacterial infection, bacterial infection alone, and neither
      viral nor bacterial infection, regarding clinical cure, relapse and reinfection
      rates. A significantly higher rate of secretory otitis media (SOM) was observed
      in alone or combined RSV infection with S. pneumonia or Haemophilus influenzae
      (H. influenzae) than in other viruses infection. Conclusion. This study provides
      information about etiologic agents and diagnosis of AOM in Turkish children. The
      findings highlight the importance of common respiratory viruses and bacterial
      pathogens, particularly RSV, HRV, S. pneumoniae and H. influenzae, in
      predisposing to and causing AOM in children.

PMID- 16967295
TI  - Inhibition of poly(ADP-ribose)polymerase does not affect the recombination events
      in CHO xrs6 and wild type cells.
AB  - Activation of poly (ADP-ribose) polymerase -1 (PARP-1) is an early DNA damage
      response event that, together with phosphorylation of p53, prompts various
      cellular functions important in the maintenance of the genome stability. In
      mammalian cells, DSB are repaired by nonhomologous end-joining (NHEJ) and by
      homologous recombination (HR). To investigate the role of PARP-1 in HR, CHO-K1
      wild type and xrs-6 mutant cell line were transfected with pLrec plasmids which
      carry two nonfunctional copies of the beta-galactosidase (lacZ) gene in a tandem
      array. In result of HR they can give rise to a functional copy of beta
      galactosidase. To test whether PARP-1 affects the frequency of spontaneous and
      induced recombination repair, we treated CHO-K1 and xrs6 clones carrying
      chromosomally integrated pLrec with the PARP-1 inhibitor 3-aminobenzamide (3AB).
      Our results show that the spontaneous homologous intrachromosomal recombination
      frequency between the two lacZ copies was almost two orders of magnitude higher
      in xrs6 cells than in CHO-K1 cells, but that it was not affected by 3AB
      treatment. Induction of DNA damage by irradiation or electroporation of
      restriction enzymes did not significantly increase the recombination frequency.
      Furthermore, in both the cell lines, the effect of PARP-1 inhibition on DSB
      repair was examined using the neutral comet assay. There was no effect of 3AB
      treatment on DSB rejoining after 10 Gy irradiation. The results presented support
      the conclusion that PARP-1 is not directly involved in HR.

PMID- 16967297
TI  - Computer tomography assessment of pedicle screw insertion in percutaneous
      posterior transpedicular stabilization.
AB  - Percutaneous insertion of cannulated pedicle screws has been recently developed
      as a minimally invasive alternative to the open technique during instrumented
      fusion procedures. Given the reported rate of screw misplacement using open
      techniques (up to 40%), we considered it important to analyze possible side
      effects of this new technique. Placement of 60 pedicle screws in 15 consecutive
      patients undergoing lumbar or lumbosacral fusion, mainly for spondylolisthesis,
      were analyzed. Axial, coronal, and sagittal reformatted computer tomography
      images were examined by three observers. Individual and consensus interpretation
      was obtained for each screw position. Along with frank penetration, we also
      looked at cortical encroachment of the pedicular wall by the screw. Thirteen
      percent of the patients (2/15) had severe frank penetration from the screws,
      while 80% of them (12/15) had some perforation. On axial images the incidence of
      severe frank pedicle penetration was 3.3% while the overall rate of screw
      perforation was 23%. In coronal images the overall screw perforation rate rose to
      30% while the rate of severe frank pedicle penetration remained unchanged. One
      patient (6.6%) suffered S1 root symptoms due to a frankly medially misplaced
      screw, requiring re-operation. This study has shown that percutaneous insertion
      of cannulated pedicle screws in the lumbar spine is an acceptable procedure. The
      overall rate of perforation in axial images is below the higher rates reported in
      the literature but does remain important. Frank penetration of the pedicle was
      nevertheless low. It remains a demanding technique and has to be performed with
      extreme care to detail.

PMID- 16967298
TI  - Effect of zoledronic acid in an L6-L7 rabbit spine fusion model.
AB  - Previous studies have shown that zoledronic acid administration can increase
      mineral content and strength in distraction osteogenesis. Of the few studies that
      have examined the use of bisphosphonates in spinal arthrodesis, none have
      assessed the effect of single dose treatment. The objective of this study was to
      evaluate the feasibility of enhancing spinal fusion rate using single dose
      zoledronic acid (ZA) to increase fusion-mass size and mineral density. Forty
      eight New Zealand white rabbits underwent an L6-L7 intertransverse process
      fusion. The L6-L7 model is more challenging than the more commonly used level of
      L5-L6. Animals were randomly allocated to one of three groups, one received iliac
      crest bone graft alone, one group received iliac crest bone graft with locally
      administered zoledronic acid, 20 microg, and one group received iliac crest bone
      graft with a single dose of systemically administered zoledronic acid, 0.1 mg/kg.
      ZA doses were administered at the time of surgery. Twenty-four rabbits were
      culled at 6 weeks and 24 rabbits were culled at 12 weeks. Success of spinal
      fusion was determined by manual palpation. Specimens were evaluated
      radiographically, underwent quantitative computerised tomography analysis and
      were tested biomechanically in flexion and extension. In the six-week group, only
      five of the 24 spines fused with no noticeable trend with respect to treatment.
      In the 12-week group there was a trend toward increased fusion in the
      systemically administered ZA group (63%) versus the other two groups (25%) but
      was not statistically significant (p = 0.15). Radiographically, the local ZA
      treatment group showed a delay in remodelling with the presence of unremodelled
      bone chips. The 12-week systemic ZA group exhibited an 86% increase in BMC, a 31%
      increase in vBMD and a 41% increase in the volume of the fusion-mass (p < 0.05).
      The 12-week local ZA group also showed significant increases in BMC (69%), vBMD
      (31%) and total fusion-mass volume (29%) (p < 0.05). Biomechanical testing showed
      that the range of motion in flexion decreased to 4.5 (+/-2.5) degrees and 4.8 (+/
      4.7) degrees for the local and systemic groups respectively compared to 9.6 (+/
      4.9) degrees for the control group (p < 0.05). This study has shown that
      zoledronic acid increased fusion-mass size and bone mineral content. Systemic ZA
      led to an increased fusion rate; however the fusion rate remained below 100%. We
      suggest that bisphosphonate treatment may require an anabolic conjunctive therapy
      to ensure enhanced successful fusion.

PMID- 16967299
TI  - Chemosensitization and radiosensitization of human lung and colon cancers by
      antimitotic agent, ABT-751, in athymic murine xenograft models of subcutaneous
      tumor growth.
AB  - PURPOSE: ABT-751 is an orally active antimitotic agent that is currently in Phase
      II clinical trials. This agent binds to the colchicine site on ss-tubulin and
      inhibits polymerization of microtubules. This disruption of microtubule dynamics
      leads to a block in the cell cycle at the G2/M phase, and promotes apoptosis. ABT
      751, as a single agent, has antitumor activity against a series of xenograft
      models including non-small cell lung cancer (NSCLC) and colon cancer. The current
      studies were conducted to determine whether ABT-751 enhances antitumor activity
      of standard cytotoxic therapies currently in clinical use. METHODS: Efficacy of
      ABT-751, in combination with cisplatin, 5-FU, and radiation, was evaluated in the
      Calu-6 NSCLC, HT-29 colon, and HCT-116 colon carcinoma xenograft models,
      respectively. Tumor-bearing athymic mice were treated with ABT-751 orally once a
      day at 75 or 100 mg/kg/day on a 5-days-on, 5-days-off schedule for two cycles.
      RESULTS: Efficacy of ABT-751 at 100 mg/kg/day was tested in combination with
      cisplatin at its maximum tolerable dose (MTD) (10 mg/kg/day, i.p. x1) in Calu-6
      tumor-bearing athymic mice. The percent treated/control (%T/C) tumor volume
      ratios on day 38 were 35, 37, and 6, and the percent tumor growth delay (%TGD)
      values were 71, 65, and 188 for cisplatin, ABT-751 and the combination groups,
      respectively. HT-29 colon tumors were used to test ABT-751 in combination with an
      MTD of 5-FU, 30 mg/kg/day, i.p., q.d. x5. The %T/C ratios on day 38 were 22, 28,
      and 5 and the %TGD values were 75, 75, and 150 for 5-FU, ABT-751, and the
      combination groups, respectively. Treatment of HCT-116 colon carcinoma tumors
      with ABT-751, concurrent with the radiation treatment, was able to both enhance
      radiation-induced tumor regression, and delay the time to recurrence and
      progression. Growth curves allowed calculation of enhancement of radiation
      induced growth delay (defined as the additional time required for a treated tumor
      to reach four times its original size) of 2, 9, and 12 days, for ABT-751 alone,
      radiation alone, and the combination, respectively. CONCLUSION: Collectively,
      these studies demonstrate that ABT-751 enhanced efficacy of standard cytotoxic
      therapies in a variety of tumor xenograft models, and that enhancement was at
      least additive in all systems.

PMID- 16967300
TI  - Effect of intervention promoting a reduction in antibiotic prescribing by
      improvement of diagnostic procedures: a prospective, before and after study in
      general practice.
AB  - OBJECTIVE: To investigate if an intervention aimed at improving the quality of
      the diagnostic procedures in Spanish general practice could lower antibiotic
      prescribing in patients with respiratory tract infections (RTIs). METHODS: GPs in
      the intervention group (n=17) registered all patients with RTIs during a 3-week
      period before and after the intervention. The intervention was aimed at reducing
      prescribing of inappropriate antibiotics for RTIs by improving the diagnostic
      procedures and thereby helping the GPs to distinguish between bacterial and viral
      infections. It consisted of courses in management of RTI according to local
      clinical guidelines, and included implementation of two rapid diagnostic tests
      (StrepA and CRP measurement). Diagnoses and prescribing of antibiotics were
      assessed before and after the intervention, and compared to a control group not
      exposed to intervention (35 GPs). RESULTS: The intervention led to a significant
      reduction in antibiotic prescribing. Before the intervention 36% (29%-44%) of
      consultations were followed by antibiotic prescribing, after the intervention 24%
      (20%-29%). Antibiotic prescribing in the control group not exposed to
      intervention was 32% (27%-38%). The reduction was most pronounced in patients
      with sinusitis and lower RTIs. CONCLUSION: Quality improvement of diagnostic
      procedures may lead to a reduction of antibiotic prescribing in primary health
      care in Spain.

PMID- 16967301
TI  - Antifungal therapy in febrile neutropenic patients: review of treatment choices
      and strategies for aspergillar infection.
AB  - RATIONALE: Invasive fungal infections, especially aspergillosis, are a major
      problem in patients who undergo aggressive therapy for haematological
      malignancies. Presently, the standard therapy for demonstrated aspergillar
      infection is voriconazole. Because the morbidity and the mortality of proven
      aspergillar infection is relatively high, empirical and preemptive approaches
      have been explored. FINDINGS: Empirical therapy is effective at the cost of
      overtreatment in a significant number of patients. This can be reduced through
      the preemptive approach; however, its equivalence in terms of successful therapy
      and mortality should be studied further and, optimally, in prospective controlled
      clinical trials.

PMID- 16967302
TI  - Incident pain and analgesic consumption decrease after samarium infusion: a pilot
      study.
AB  - OBJECTIVE: The aim of this pilot study was to observe the variations of pain
      intensity on movement and at rest and the variation of analgesic drug consumption
      in patients with prostate cancer and painful bone metastases treated with a
      single dose of 1.0 mCi/kg of samarium-153 (153-Sm) lexidronam. DESIGN: Case
      series. SETTING: The Nuclear Medicine Unit and Pain Therapy and Palliative Care
      Unit, National Cancer Institute of Milan, Italy. PATIENTS: Thirteen outpatients
      with hormone refractory prostate cancer and painful multiple bone metastases.
      INTERVENTIONS: Infusion of a single dose of 1.0 mCi/kg of 153-Sm lexidronam, pain
      therapy, and the assessment of pain intensity at rest and on movement. MAIN
      OUTCOME MEASURES: Variation of pain intensity on movement and at rest by means of
      a verbal scale and the reduction of analgesic drug consumption 4 weeks after
      infusion of 153-Sm lexidronam. RESULTS: From baseline, 61.5% of patients reported
      a decrease of at least two levels of pain intensity on movement and 53.8% of
      patients had an improvement of pain at rest. Of the patients, 15.4% were not in
      pain at rest or on movement at baseline and continued to be free of pain 4 weeks
      after the administration of samarium. All ten patients, but one, who were on
      analgesic drugs before samarium infusion, reduced the regular drug administration
      or rescue medication. Bone marrow toxicity was mild and readily reversible in
      three patients. CONCLUSIONS: In patients with bone metastases, pain on movement
      is a frequent and often difficult clinical problem to treat and the most frequent
      cause of breakthrough pain. In patients with painful multiple bone metastases due
      to prostate cancer, the infusion of a single dose of 1.0 mCi/kg of 153-Sm
      lexidronam may be considered an effective and safe treatment for pain either at
      rest or during movement.

PMID- 16967303
TI  - Life review interviews on the spiritual well-being of terminally ill cancer
      patients.
AB  - GOALS: The aims of this study were (1) to evaluate the treatment efficacy of life
      review interviews on the spiritual well-being of terminally ill cancer patients,
      and (2) to explore any differences in the responses of patients who obtained
      clinical benefits and those who did not. MATERIALS AND METHODS: Structured life
      review interviews were conducted with 12 patients in a palliative care unit in
      Japan. They completed the SELT-M (Skalen zur Erfassung von Lebens qualitat bei
      Tumorkranken-Modified Version) questionnaire before and after the interviews. The
      patients were classified into two groups: effective (patients who showed an
      increase in the SELT-M scores after the intervention) and noneffective groups.
      Meaningful spoken sentences from the patients' life reviews were transcribed and
      correspondence analysis was conducted on the sentences using text mining
      software. RESULTS: The mean overall QOL score and spirituality subscale score of
      the SELT-M significantly increased after the life reviews from 2.57+/-0.61 to
      3.58+/-1.0 (P=0.013) and 2.57+/-0.61 to 3.14+/-2.25 (P=0.023), respectively.
      Three dimensions were extracted from the effective group based on the scores
      "Positive view of life," "Pleasure in daily activities and good human
      relationships," and "Balanced evaluation of life." Similarly, three dimensions
      were extracted from the noneffective group: "Worries about future caused by
      disease," "Conflicts in family relationship problems," and "Confrontation of
      practical problems." CONCLUSION: Life review interviews may be effective in
      improving the spiritual well-being of terminally ill cancer patients. The
      potential predictors of treatment success are "positive view of life," "pleasure
      in daily activities and good human relationships," and a "balanced evaluation of
      life," while those of treatment failure are "worries about future caused by
      disease," "conflicts in family relationships," and "confrontation of practical
      problems." Further intervention trials on patients with predictors of treatment
      success are promising.

PMID- 16967304
TI  - The ntp operon encoding the Na+ V-ATPase of the thermophile Caloramator fervidus.
AB  - The V-type ATPase of the thermophile Caloramator fervidus is an ATP-driven Na+
      pump. The nucleotide sequence of the ntpFIKECGABD operon containing the
      structural genes coding for the nine subunits of the enzyme complex was
      determined. The identity of the proteins in two pairs of subunits (D, E and F, G)
      that have very similar mobilities on SDS-PAGE of the purified complex (24.3 and
      22.7 kDa, and 12.3 and 11.6 kDa) was established by tryptic digestion of the
      protein bands followed by mass spectrometric analysis of the peptides.

PMID- 16967305
TI  - Temperature modifies the health effects of particulate matter in Brisbane,
      Australia.
AB  - A few epidemiological studies have examined whether there was an interactive
      effect between temperature and ambient particulate matter on cardiorespiratory
      morbidity and mortality, but the results were inconsistent. The present study
      used three time-series approaches to explore whether maximum temperature modified
      the impact of ambient particulate matter less than 10 microm in diameter (PM(10))
      on daily respiratory hospital admissions, cardiovascular hospital admissions,
      respiratory emergency visits, cardiovascular emergency visits, non-external cause
      mortality and cardiovascular mortality in Brisbane between 1996 and 2001. The
      analytical approaches included a bivariate response surface model, a non
      stratification parametric model and a stratification parametric model. Results
      show that there existed a statistically significant interaction between PM(10)
      and temperature on most health outcomes at various lags. PM(10) exhibited more
      adverse health effects on warm days than cold days. The choice of the degree of
      freedom for smoothers to adjust for confounders and the selection of arbitrary
      cut-offs for temperature affected the interaction estimates to a certain extent,
      but did not change the overall conclusion. The results imply that it is important
      to control and reduce the emission of air particles in Brisbane, particularly
      when temperature increases.

PMID- 16967306
TI  - Purinoceptor expression on keratinocytes reflects their function on the epidermis
      during chronic venous insufficiency.
AB  - Purines are extracellular nucleotides that have long-term effects on keratinocyte
      proliferation, differentiation and death through P2Y(1), P2Y(2), P2X(5) and
      P2X(7) receptors. This study examined changes in expression of these P2 receptors
      on lower leg epidermal keratinocytes in control and chronic venous insufficiency
      (CVI) states. Lower limb skin biopsies from CVI (CEAP classification 4a and 4b)
      and control skin were immunostained for the above P2 receptor subtypes and
      epidermal area was calculated. Our results with CVI show an increase in P2Y(1)
      and P2Y(2) receptor expression in basal and spinosal layers of the epidermis and
      an increase of P2X(5) receptors mainly in the spinosal layer and extending
      further into the stratum granulosum. In contrast, P2X(7) receptors were reduced
      in the stratum corneum in CVI. In conclusion, a thinner epidermis was found in
      CVI, which might be the result of the changes in expression of P2Y and P2X
      receptors on keratinocytes: that is, increased proliferation via P2Y(1) and
      P2Y(2) receptors and reduced P2X(7) receptor-mediated cell death opposed by a
      dominant decrease in cell numbers as a result of increased P2X(5) receptor
      mediated differentiation (which is in effect antiproliferative). Thus, increased
      keratinocyte P2X(5) receptor activity may, in part, be accountable for epidermal
      thinning in CVI.

PMID- 16967307
TI  - Kinetics of blood flow after topical application of benzyl nicotinate on
      different anatomic sites.
AB  - Cutaneous characteristics, e.g., thickness of the SC and density of follicles,
      affect the penetration of topically applied substances. In the present study, the
      penetration of benzyl nicotinate, causing a vasodilation, was studied on three
      anatomic sites (forearm, forehead and calf) differing in their skin
      characteristics. Therefore, the blood flow of the superficial dermal plexus and
      that of the larger capillaries in the deeper skin layers was simultaneously
      measured using a laser Doppler flowmeter. In addition, the cutaneous temperature
      and redness were determined as a function of time. These four biological
      reactions were measured in turn on a skin area treated with a gel containing
      benzyl nicotinate and on an untreated control area. The highest basal levels were
      observed on the forehead. Topical application of benzyl nicotinate resulted in an
      increase in each biological response. Compared to the other sites, the maximal
      values were reached earliest on the forehead, which also showed the fastest
      decrease. No significant differences were obtained comparing the kinetic data of
      the calf with that of the forearm. The results indicate an additional
      contribution by the numerous vellus hair follicles of the forehead to the
      penetration and exposure of the drug.

PMID- 16967308
TI  - Muscle sparing thoracotomy in pediatric age: a comparative study with standard
      posterolateral thoracotomy.
AB  - Alternative approaches to the standard posterolateral incision for thoracotomy
      have been developed to minimize its postoperative pain and wound related side
      effects. Muscle-sparing (MS) thoracotomy has been a well-known substitution to
      the standard posterolateral thoracotomy for this purpose; however it has not been
      studied in the pediatric age group in detail. We studied retrospectively the
      patients with thoracotomy for non-cardiac, thoracic surgical procedures. Group 1
      included the patients with standard posterolateral thoracotomy for the surgery.
      The patients with MS thoracotomy composed group 2. The related data were
      collected retrospectively. The early postoperative morbidities (time requiring
      for regaining shoulder girdle movement, extubation, intensive care unit stay, and
      hospital stay) and late musculoskeletal anomalies (scoliosis, elevation of the
      shoulder, winged scapula, asymmetry of the nipples) were compared between groups.
      A total of 90 patients were included in the study. Group 1 constituted 50
      patients with an average age of 4.24 +/- 2.91 years. Group 2 included 40 patients
      with an average age of 4.20 +/- 2.92 years. Comparison of the demographics and
      the baseline characteristics of the patients were not different between groups.
      In comparison of operative characteristics, there was lesser morbidity in group 2
      as re-exploration for bleeding, wound infection, wound healing and fewer
      intensive care unit and hospital stay days. Late follow-up revealed a significant
      increase in musculoskeletal deformities in group 1. We conclude that muscle
      sparing incision should be preferred to the standard posterolateral thoracotomy
      in pediatric age.

PMID- 16967309
TI  - Bleeding duodenal varices successfully treated with TIPS.

PMID- 16967310
TI  - De novo hepatocellular carcinoma occurring in a transplanted liver: case report
      and review of the literature.

PMID- 16967311
TI  - Bifidobacterial diversity determined by culturing and by 16S rDNA sequence
      analysis in feces and mucosa from ten healthy Spanish adults.
AB  - This study aimed to identify the numerically predominant bifidobacterial species
      in feces and mucosa of healthy Spanish people and to determine their phenotypic
      and genetic diversity. To this end, both traditional culturing and molecular
      methods were used. A set of 196 bifidobacterial colonies was identified from the
      counting plates by sequencing of a stretch of their 16S rRNA gene. Representative
      isolates were phenotypically characterized by their carbohydrate fermentation
      profile and genotypically typed by RAPD-PCR. Four 16S rDNA libraries composed of
      113 clones from two fecal and two mucosal samples were independently analyzed.
      Seven bifidobacterial species were identified by culturing, and six by 16S rDNA
      analysis. Both methodologies showed Bifidobacterium longum and B.
      pseudocatenulatum to predominate in feces and mucosa, although high
      interindividual variability was noted. High phenotypic variation was observed in
      the fermentation profile of different isolates from the same species. RAPD
      analysis showed that two to five strains made up the subjects' personal
      bifidobacterial communities. The identification of the dominant bifidobacterial
      species could be useful for the rational design, use, and evaluation of
      probiotics in our community.

PMID- 16967312
TI  - Multilayered epithelium may be found in patients with Barrett's epithelium and
      dysplasia or adenocarcinoma.
AB  - To determine if multilayered epithelium (MLE) is a useful prognostic indicator
      for a benign natural history of Barrett's epithelium, we evaluated endoscopic
      biopsies from patients with Barrett's epithelium without and with dysplasia
      and/or adenocarcinoma and from non-Barrett's controls for the presence of MLE.
      MLE was found in 6% of non-Barrett's controls, 30% of Barrett's patients with no
      dysplasia, and 14% of Barrett's patients with dysplasia and/or adenocarcinoma.
      MLE was significantly associated with shorter lengths of Barrett's epithelium in
      both Barrett's groups. Three of 5 photodynamic therapy patients were noted to
      develop MLE after therapy. MLE may be found in patients with dysplasia and/or
      adenocarcinoma and after photodynamic therapy; its presence is not useful as a
      prognostic indicator for a more benign course of Barrett's. This study confirms
      that MLE is significantly associated with shorter lengths of Barrett's
      epithelium.

PMID- 16967313
TI  - Incidental small ampullary somatostatinoma treated with ampullectomy 2 years
      after diagnosis.
AB  - Somatostatinomas are rare tumors; ampullary somatostatinomas are very rare. We
      report a case of a small pure somatostatin-producing neuroendocrine tumor of
      ampulla of Vater in a 54-year-old woman with neither neurofibromatosis nor
      somatostatinoma syndrome, "incidentally" discovered during an abdominal computed
      tomography. The patient initially refused other adjunctive exams but after 2
      years she was admitted, presenting with itch, night sweats, severe fatigue, and
      unintentional weight loss. The size of the tumor (1.5 cm) and the other
      radiologic findings had not changed since the abdominal CT scan 2 years before.
      The somatostatin, gastrin, glucagons, serotonin, vasoactive intestinal peptide,
      dopamine, norepinephrine, epinephrine, and calcitonin plasma levels were normal.
      ERCP-obtained biopsies revealed a neuroendocrine tumor with psammoma bodies;
      immunohistochemical profile was positive for chromogranin and somatostatin. The
      patient underwent surgery; intraoperative histologic examination of lymph nodes
      sampling of perihepatic and periduodenal lymph nodes was negative for metastasis.
      We performed, therefore, a transduodenal ampullectomy. The patient continues to
      do well at 3 years' follow-up with no evidence of local or distance recurrence of
      disease.

PMID- 16967314
TI  - Primary solitary extragastrointestinal stromal tumor of the greater omentum
      coexisting with ulcerative colitis.

PMID- 16967315
TI  - Peripheral neurological disturbances, autonomic dysfunction, and antineuronal
      antibodies in adult celiac disease before and after a gluten-free diet.
AB  - Thirty-two consecutive adult celiac disease (CD) patients (pts), complaining of
      peripheral neuropathy (12 pts), autonomic dysfunction (17 pts), or both (3 pts),
      were evaluated to assess the presence of neurological damage (by clinical
      neurological evaluation and electrophysiological study) and antineuronal
      antibodies and to assess the effect of a gluten-free diet (GFD) on the course of
      the neurological symptoms and on antineuronal antibodies. At entry, 12 of 32
      (38%) pts showed signs and symptoms of neurological damage: 7 of 12 (58%),
      peripheral neurological damage; 3 of 12 (25%), autonomic dysfunction; and 2
      (17%), both peripheral neurological damage and autonomic dysfunction. The overall
      TNS score was 105 at entry. Anti-GM1 antibodies were present in 5 of 12 (42%)
      pts: 3 showed peripheral neurological damage and 2 showed both peripheral
      neurological damage and autonomic dysfunction. One year after the GFD was
      started, histological lesions were still present in only 10 of 12 (83%) pts. TNS
      score was 99, 98, 98, and 101 at the 3rd, 6th, 9th, and 12th month after the GFD
      was started, so it did not improve throughout the follow-up. None of the pts
      showed disappearance of antineuronal antibodies throughout the follow-up. We
      conclude that adult CD patients may show neurological damage and presence of
      antineuronal antibodies. Unfortunately, these findings do not disappear with a
      GFD.

PMID- 16967316
TI  - ESR spectroscopy investigation of the denaturation process of soybean peroxidase
      induced by guanidine hydrochloride, DMSO or heat.
AB  - The involvement of protein denaturation and/or misfolding processes in the
      insurgence of several diseases raises the interest in structural dynamic studies
      of proteins. The use of nitroxide spin labels with electron paramagnetic
      resonance is a powerful tool for detecting structural changes in proteins. In the
      present study, we apply this strategy to soybean peroxidase (SBP), a protein
      characterised by high thermal and structural stability, and we propose a simple
      method to analyse the anisotropy changes of the protein system and to relate them
      with the structural changes induced by protein unfolding. We examined the effect
      of temperature, guanidine hydrochloride and dimethylsulfoxide on the stability of
      SBP and looked for correlations between the ESR results and the experimental
      findings obtained by other techniques, reported in the literature. The agreement
      between data obtained through different strategies supports the validity and
      reliability of the ESR approach to protein unfolding.

PMID- 16967317
TI  - Analysis of chameleon sequences by energy decomposition on a pairwise per-residue
      basis.
AB  - The conversion from alpha-helix to beta-strand that has been widely observed in
      so-called chameleon sequences has received considerable attention since such a
      structural change may induce many amyloidogenic proteins to self-assemble into
      fibrils thus causing fatal diseases. Here we report a large scale-analysis of the
      energetics of secondary structural conversions in a collection of chameleon
      sequences retrieved from the Protein Data Bank. Major energetic contributions to
      the secondary structural conversion were analyzed by carrying out energy
      decomposition on a pairwise per-residue basis, i.e., (i,i), (i,i +/- 1), (i,i +/-
      2), (i,i +/- 3), (i,i +/- 4) and > (i,i +/- 4) intra-/inter-residual
      interactions. While the overall potential energy differences were subtle,
      individual residue-based interacting energy differences were observed to vary
      significantly depending on the specific type of secondary structural conversion.
      The average energy difference between alpha-helix and beta-strand, <DeltaE (alpha
      ->beta)>, in the chameleon sequences varied significantly in (i,i), (i,i +/- 1)
      and > (i,i +/- 4) interactions. The major energetic factors in secondary
      structure conversions were electrostatic interactions and the polar term for
      solvation energy. In addition, residue-based average energy differences in alpha
      helix --> beta-strand conversions were well-correlated to those in alpha-helix -
      > random coil --> beta-strand conversions (R2 = 0.92). Assuming that three
      secondary structural elements can transform in either direction, this strong
      correlation indicates that the present energy decomposition method using database
      structures of chameleon sequences provides a reliable tool for the
      characterization of secondary structure fluctuations in amino acid sequences.

PMID- 16967318
TI  - Primary structure of myostracal prism soluble protein (MPSP) in oyster shell,
      Crassostrea gigas.
AB  - Soluble protein (MPSP, myostracal prism soluble protein) obtained from myostracum
      in oyster shell (Crassostrea gigas) was characterized using biochemical and
      molecular biological techniques. From an analysis of secondary protein structure,
      it was shown that beta-structure was predominant in MPSP. And via in vitro
      assays, the relation of MPSP to biomineral phase and morphology was studied. SDS
      PAGE revealed one major protein band of 20 kDa. An amino acid sequence of 160
      amino acids was deduced for myostracum by characterization of the complementary
      DNA encoding the protein. The deduced protein was composed of a high proportion
      of Gly and Asp, typifying a calcium-binding protein for shell formation, and a
      relatively high proportion of Val, Ala and Ile, typifying an adhesive protein. In
      contrast to prevailing expectations, (Gly-Asp)n-type sequence motifs exist in
      MPSP, demanding a revision of previous theories of protein-mineral interactions.
      The cDNA sequence of myostracum is elucidated for the first time.

PMID- 16967319
TI  - Delayed fluorescence and phosphorescence of 8-aza-D-homogonane in the gas and
      condensed phases.
AB  - The delayed fluorescence spectrum for 8-aza-D-homogonane in the gas phase
      consists of a band of E-type delayed fluorescence of M-centers and a band of P
      type delayed fluorescence of L-centers being the products of photo- and
      thermotransformations of a basic steroid. Triplet-triplet energy transfer from
      the M-centers to the L-centers is established and its efficiency is determined.
      For 8-aza-D-homogonane in frozen hexane solutions at T=77 K only the
      phosphorescence of the M- and L-centers is revealed. The phosphorescence of the
      basic steroid itself (lambda(max)(phos) = 415 nm) as well as that of the M- and L
      centers (lambda(max)(phos) = 498 and 532 nm, respectively) is seen in a mixture
      of frozen tetrahydrofuran and toluene solutions. This is evident of the fact that
      the basic steroid has the products of its transformations, whose amount grows due
      to irradiation and heating. The M- and L-centers are stable molecules.

PMID- 16967320
TI  - Luminescent behavior of two novel thermo-sensitive poly(N-isopropylacrylamide)
      hydrogels incorporated with rare earth complexes.
AB  - Two novel luminescent temperature-sensitive poly(N-isopropylacrylamide) hydrogels
      fabricated with rare earth (Eu, Tb) picolinic acid complexes were in-situ
      synthesized within the interpenetration networks. Fluorescence spectra indicate
      the two functional gels exhibit red for Eu3+ species and green emissions for Tb3+
      ones, respectively, whose luminescence intensities are changed due to temperature
      increasing from 5 to 30 degrees C until totally quenched at lower critical
      solution temperature (33 degrees C). In addition, the decreasing luminescence
      behavior obeys the simple linear equations. The releasing experiment
      substantiates that there may be complexation between O=C-NH- moieties of P-NIPAA
      and Eu3+ ions for the prolonged released time.

PMID- 16967321
TI  - Counterstaining improves visualization of the myenteric plexus in immunolabelled
      whole-mount preparations.
AB  - Immunocytochemistry has emerged as a powerful research tool in neurobiology. One
      of the widely used methods is an indirect fluorescence technique that uses FITC-
      conjugated IgG to visualise protein expression within tissues, but a major
      drawback of this technique is the high background fluorescence due to non
      specific antibody binding. Gut innervation is complex and best visualized in
      three-dimensions in whole mount preparations. We describe a simple and easy to
      use counterstaining procedure in conjunction with an indirect immunofluorescence
      technique in gut whole mount preparations that largely eliminates background
      fluorescence and creates a contrasting background against the bright antigen
      antibody complexes. Furthermore, this technique allows the detailed qualitative
      and quantitative study of myenteric plexuses in whole-mount preparations.

PMID- 16967322
TI  - Spectrophotometric characteristics of new pyridylindolizine derivatives
      solutions.
AB  - Three new pyridylindolizine derivatives, 1, 2, 3-tricarbometoxi-7-(4-pyridyl)
      pyrrolo[1, 2-a]pyridine (I), 1,2-dicarboethoxy-3-(4-bromobenzoyl)-7-(4-pyridyl)
      pyrrolo[1,2-a]pyridine (II) and its isomer 1,2-dicarboethoxy-3- (4-bromobenzoyl) 
      5- (2-pyridyl) -pyrrolo[1, 2-a]pyridine (III) have been investigated in different
      solutions by UV-VIS absorption, steady-state, and time-resolved fluorescence
      methods. The effects of the substituent and solvent on the spectroscopic
      properties have been demonstrated. The fluorescence decay data could be fitted to
      a single-exponential function. The lifetime values are higher in protic polar
      than in aprotic apolar solvents for compound I. In the case of compounds II and
      III the fluorescence intensities and lifetimes are very low, with the exception
      of III in aprotic solvents. The absorption and fluorescence properties of the
      compounds showed a solvent dependence.

PMID- 16967323
TI  - Ex-vivo analysis of CD8+ T cells infiltrating colorectal tumors identifies a
      major effector-memory subset with low perforin content.
AB  - Previous studies have indicated that the infiltration of CD8+ T cells in
      colorectal cancer is an independent predictor of increased survival but clinical
      observations have suggested that the cytotoxic function of CD8+ T cells
      infiltrating colorectal cancer may often be limited. In this study, we have
      assessed the phenotype of colorectal cancer CD8+ tumor-infiltrating lymphocytes
      (TILs) isolated ex vivo from tumor tissue, and assessed the perforin content of
      TIL with respect to their location using immunohistochemistry. We found that CD8+
      T cells TILs isolated from colorectal cancer are mainly composed of antigen
      experienced cells of effector memory type (TEM, CD45RA-CCR7-, and CD27+/CD28- or
      CD27-/CD28-), and contain only minor proportions of terminally differentiated
      CD8+ T cells (TEMRA, CD45RA+CCR7-). The perforin content of these TILs, however,
      is significantly lower than that of antigen-experienced T cells in PBMCs due to
      the much lower levels of perforin found in the CD27-CD28- subset in TILs compared
      with CD8+ T cells of similar phenotype in PBMCs.

PMID- 16967324
TI  - Does totally endoscopic access for off-pump cardiac surgery influence the
      incidence of postoperative atrial fibrillation in coronary artery bypass
      grafting? A preliminary report.
AB  - BACKGROUND: The occurrence rate of atrial fibrillation (AF) after coronary artery
      bypass grafting, quoted in the literature, is wide ranging from 5% to over 40%.
      It is speculated that, off-pump coronary artery bypass grafting (OPCAB) and also
      minimally invasive cardiac surgery reduces the incidence of postoperative AF due
      to reduced trauma, ischemia, and inflammation. Current data, however, do not
      clearly answer the question, whether the incidence of postoperative AF is reduced
      in using minimally invasive techniques, ideally resulting in the combination of
      both small access and off-pump surgery. The aim of this study was to evaluate the
      incidence of postoperative AF in patients undergoing totally endoscopic off-pump
      coronary artery bypass grafting (TECAB). METHODS: A retrospective analysis of 72
      patients undergoing myocardial revascularization was performed. Early
      postoperative incidence of AF was compared between three groups of patients: 24
      after conventional coronary artery bypass grafting (CABG), 24 after OPCAB, and 24
      after totally endoscopic off-pump CABG. Clinical profile of the patients,
      including factors having potential influence on postoperative AF was matched for
      groups. RESULTS: Postoperative AF occurred in 25% of the patients in the CABG
      group, in 16% of the patients in the OPCAB group, and in 16% of the patients in
      the TECAB group. This difference has no statistical significance. Risk factors
      and incidence of postoperative complications were comparable in all groups
      excepting the number of distal anastomoses. There was a statistical significance
      between CABG group and TECAB group. CONCLUSION: Avoiding cardiopulmonary bypass
      and minimizing surgical trauma did not reduce the incidence of postoperative AF
      in this patient collective. It remains an attractive hypothesis that
      postoperative AF is reduced by off-pump myocardial revascularisation and
      minimizing surgical trauma but more robust data are required.

PMID- 16967325
TI  - A combined FEM/genetic algorithm for vascular soft tissue elasticity estimation.
AB  - Tissue elasticity reconstruction is a parameter estimation effort combining
      imaging, elastography, and computational modeling to build maps of soft tissue
      mechanical properties. One application is in the characterization of
      atherosclerotic plaques in diseased arteries, wherein the distribution of elastic
      properties is required for stress analysis and plaque stability assessment. In
      this paper, a computational scheme is proposed for elasticity reconstruction in
      soft tissues, combining finite element modeling (FEM) for mechanical analysis of
      soft tissues and a genetic algorithm (GA) for parameter estimation. With a model
      reduction of the discrete elasticity values into lumped material regions, namely
      the plaque constituents, a robust, adaptive strategy can be used to solve inverse
      elasticity problems involving complex and inhomogeneous solution spaces. An
      advantage of utilizing a GA is its insistence on global convergence. The
      algorithm is easily implemented and adaptable to more complex material models and
      geometries. It is meant to provide either accurate initial guesses of low
      resolution elasticity values in a multi-resolution scheme or as a replacement for
      failing traditional elasticity estimation efforts.

PMID- 16967326
TI  - Role of tumor-associated macrophages in tumor progression and invasion.
AB  - Tumor-Associated Macrophages (TAM) represent the major inflammatory component of
      the stroma of many tumors, able to affect different aspects of the neoplastic
      tissue. Many observations indicate that TAM express several M2-associated
      protumoral functions, including promotion of angiogenesis, matrix remodelling and
      suppression of adaptive immunity. The protumoral role of TAM in cancer is further
      supported by clinical studies that found a correlation between the high
      macrophage content of tumors and poor patient prognosis and by evidence showing
      that long-term use of non-steroidal anti-inflammatory drugs reduces the risk of
      several cancers. Here, we discuss evidence supporting the view that TAM represent
      a unique and distinct M2-skewed myeloid population and a potential target of anti
      cancer therapy.

PMID- 16967327
TI  - Gender, threat/control-override delusions and violence.
AB  - This study brings together the threat/control-override perspective and the
      literature on gender and stress coping to argue that gender moderates the
      association between threat delusions and violence. We suggest that men are more
      likely than women to respond to stressors such as threat delusions with violence.
      We test these ideas using data from the MacArthur Violence Risk Assessment Study,
      a multi-wave study of post-discharge psychiatric patients. Within-person results
      from two-level hierarchical models support the idea that men and women cope with
      threat delusions differently. Specifically, we find that men are significantly
      more likely to engage in violence during periods when they experience threat
      delusions, compared with periods when they do not experience threat delusions. In
      contrast, women are significantly less likely to engage in violence during times
      when they experience threat delusions, compared with periods when they do not. We
      discuss these findings in light of the literature on gender and stress coping.

PMID- 16967328
TI  - Symptom overreporting and recovered memories of childhood sexual abuse.
AB  - The authenticity of recovered memories is a much debated issue. Surprisingly, no
      study has systematically looked at symptom overreporting in people claiming
      recovered memories of childhood sexual abuse (CSA). In a first sample we
      administered the Structured Inventory of Malingered Symptomatology (SIMS) to
      individuals who said they had recovered CSA memories (n=66), individuals who said
      their CSA had always been accessible (continuous CSA memory group; n=119), and
      controls who said they had no CSA experiences (n=83). In a second sample
      individuals reporting recovered (n=45) or continuous (n=45) CSA memories
      completed the Morel Emotional Numbing Test (MENT). Our aim was to compare these
      groups with regard to their tendency to overreport symptoms. The results indicate
      that people with recovered memories do not score higher on the SIMS and the MENT
      than other CSA survivors suggesting that symptom overreporting is not typical for
      people reporting recovered memories.

PMID- 16967329
TI  - Prisoners' positive illusions of their post-release success.
AB  - Prisoners' forecasts of post-release success may have implications for how they
      respond to imprisonment, release, and parole decisions. We examined sentenced US
      and UK prisoners' forecasts of recidivism, and how well UK prisoners believed
      they would fare compared to the average other prisoner. In both samples,
      forecasts of recidivism were unrealistically optimistic when compared to official
      statistics on recidivism. UK prisoners also demonstrated a self-enhancement bias
      by forecasting that they were less likely to re-offend than other prisoners.
      Prisoners' forecasts of recidivism were predicted by only a few of the pre
      prison, in-prison, and post-prison factors that have been shown to be associated
      with actual recidivism. We discuss the implications of these findings and propose
      avenues for future research.

PMID- 16967330
TI  - Visioning family-centered care in genetics: what parents and providers have to
      say.
AB  - The purpose of this multisite exploratory research study involving focus groups
      of consumers and service providers was to generate stakeholder input for a
      statewide strategic plan for genetic services in the southwestern region of the
      United States. This article describes the qualitative methods by which the data
      were collected and summarizes major themes in participants' perceptions about
      genetic services. It also describes processes related to obtaining genetic
      services and characteristics of an ideal service delivery system for children
      affected by genetic disorders and the families that care for them. Implications
      for practice and policy are also reviewed.

PMID- 16967331
TI  - Depression and suicidal ideation after predictive testing for Huntington's
      disease: a two-year follow-up study.
AB  - The present study reports a two-year follow-up of psychological effects of
      predictive testing for Huntington's disease. Questionnaires assessing depression,
      general health, well-being, self injurious behavior, life satisfaction, and
      lifestyle were completed by 35 carriers and 58 non-carriers before the predictive
      test, and 2, 6, 12, and 24 months afterwards. Both carriers and non-carriers
      showed high suicidal ideation before the predictive testing. Depression scores
      and frequency of suicidal thoughts increased for carriers, compared to non
      carriers, over time. There were no differences regarding life satisfaction or
      life style between carriers and non-carriers. Predictive testing was beneficial
      in reducing overall ill-health symptoms and increasing well-being for those
      initially expressing concern about Huntington's disease. The importance of
      assessing suicidal ideation and of continuing to provide adequate support is
      emphasized.

PMID- 16967332
TI  - Development of a communication aid to facilitate risk communication in
      consultations with unaffected women from high risk breast cancer families: a
      pilot study.
AB  - The literature on risk perception in women from high-risk breast cancer families
      reveals persistent over-estimation of risk, even after counseling. In this study,
      a communication aid was designed to facilitate discussion of risk between
      clinical geneticists and genetic counselors and women from this high-risk
      population. METHOD: Stage 1. The aid was developed by an expert panel of clinical
      geneticists, genetic counselors, psychologists, an epidemiologist, an oncologist,
      linguists and a consumer. It was guided by the international literature on risk
      communication and a large multi-centre Australian study of risk communication.
      The 13 page full-color communication aid used varying formats of words, numbers,
      graphs and pie-charts to address (a) the woman's subjective risk; (b) the
      population risk of breast cancer; c) the risk of inherited breast cancer; (d) the
      cumulative risk for women with BRCA1 and BRCA2 mutations; (e) family risk
      factors; (f) the woman's suitability for genetic testing; (h) screening and
      management recommendations, and (i) a re-assessment of the woman's subjective
      risk. Stage 2: A before-after pilot study of 38 women who were unaffected with
      breast cancer and were attending four Australian familial cancer clinics was
      undertaken. Baseline and follow-up questionnaires were completed by 27 women.
      Outcomes were compared to those observed in 107 similar women undergoing genetic
      counseling without the communication aid in 2001. RESULTS: The risk communication
      aid appears to be beneficial; breast cancer genetics knowledge improved in some
      areas and importantly, risk perceptions improved in the cohort receiving the
      communication aid. Psychological measures showed no difference in anxiety or
      depression between the group receiving the communication aid and the comparison
      cohort. Women and clinicians were very positive about the usefulness of the
      communication aid as an adjunct to the genetic counseling consultation.

PMID- 16967334
TI  - Autoantibodies against an extracellular peptide of the GluR3 subtype of AMPA
      receptors activate both homomeric and heteromeric AMPA receptor channels.
AB  - Autoantibodies to the GluR3-subtype of AMPA/glutamate receptors are found in the
      sera and cerebrospinal fluid of some individuals with epilepsy. They could
      possibly play a role in the pathophysiology of epilepsy since anti-GluR3 sera
      display glutamatergic agonist activity. We have investigated here the ability of
      affinity-purified antibodies (Abs) directed against the immunogenic peptide
      GluR3B (amino-acid 372-395) to interact with and activate recombinant GluR3
      receptor channels expressed by Xenopus oocytes. We report here that the affinity
      purified anti-GluR3B Abs directly activate GluR3-containing homomeric and
      heteromeric AMPA receptor complexes without the requirement of neuronal, glial or
      blood ancillary molecules. We present some of the properties of the purified anti
      GluR3B Abs and discuss the possible physiological or pathological consequences of
      their activation of glutamate receptors.

PMID- 16967333
TI  - Workplace interventions for workers with musculoskeletal disabilities: a
      descriptive review of content.
AB  - BACKGROUND: Despite the convergence of scientific data to the effect that
      interventions in the workplace promote a healthy return to work, the
      interventions carried out in the real work environment appear to be very
      heterogeneous and ill-defined. OBJECTIVE: The goal of this review is to identify
      the different objectives pursued through the workplace interventions carried out
      in the context of a rehabilitation program, and to describe the activities
      involved. METHODS: A descriptive review of the literature, including various
      research designs, was carried out. RESULTS: This review reveals great
      heterogeneity in the content of interventions offered in the workplace to workers
      with musculoskeletal disabilities. The objectives of workplace interventions may
      range from gathering information in order to reproduce work demands in a clinical
      setting, to gradually exposing workers to the demands of the real work
      environment, or permanently reducing the demands of the work situation. A
      descriptive analysis of the literature also brings to light the diversity of
      actions carried out, human resources used, and workplace environments involved,
      while highlighting the few documented process outcome evaluations that have been
      done of workplace interventions. CONCLUSION: It is recommended that in future
      research in this area, efforts be made to better describe the components of the
      interventions, to develop process outcomes representing the multidimensional
      results obtained in the workplace, and to differentiate between temporary and
      permanent modifications made to the work situation.

PMID- 16967335
TI  - Genetic and environmental influences on schizotypy among adolescents in Taiwan: a
      multivariate twin/sibling analysis.
AB  - This study aimed to examine the relative contribution of genes and environment to
      psychometrically measured schizotypy and the causes for the covariation between
      different dimensions of schizotypy in a total of 330 pairs of twins and 36 same
      sex sib-pairs aged 12-16 and systematically recruited from junior high schools in
      Taipei. Twins' zygosity was determined by a combination of DNA typing and
      physical similarity. Schizotypy was measured using the Perceptual Aberration
      Scale (PAS) as well as the Schizotypal Personality Questionnaire (SPQ) and its
      three factors (Cognitive-perceptual Dysfunction, Disorganization, and
      Interpersonal Dysfunction). Univariate analyses of structural equation modeling
      using Mx program showed that scores on these schizotypal measures were
      substantially heritable (h (2) ranging from 41 to 49%), with some genetic effects
      being non-additive. Multivariate analyses revealed common genetic factors linking
      between various traits of schizotypy, with bivariate heritability ranging from 50
      to 65%. The proportion of the genetic contributions not shared with the other
      measures of schizotypy ranged from 24% for the Disorganization to 49% for the PAS
      scores. We concluded that there exist both common and specific genetic factors
      between the various dimensions of schizotypy, and at least half of their
      correlations were genetic in nature.

PMID- 16967336
TI  - Conduct problems, depressive symptomatology and their co-occurring presentation
      in childhood as predictors of adjustment in early adolescence.
AB  - The present study investigated patterns in the development of conduct problems
      (CP), depressive symptoms, and their co-occurrence, and relations to adjustment
      problems, over the transition from late childhood to early adolescence. Rates of
      depressive symptoms and CP during this developmental period vary by gender; yet,
      few studies involving non-clinical samples have examined co-occurring problems
      and adjustment outcomes across boys and girls. This study investigates the
      manifestation and change in CP and depressive symptom patterns in a large,
      multisite, gender-and ethnically-diverse sample of 431 youth from 5th to 7th
      grade. Indicators of CP, depressive symptoms, their co-occurrence, and adjustment
      outcomes were created from multiple reporters and measures. Hypotheses regarding
      gender differences were tested utilizing both categorical (i.e., elevated symptom
      groups) and continuous analyses (i.e., regressions predicting symptomatology and
      adjustment outcomes). Results were partially supportive of the dual failure model
      (Capaldi, 1991, 1992), with youth with co-occurring problems in 5th grade
      demonstrating significantly lower academic adjustment and social competence two
      years later. Both depressive symptoms and CP were risk factors for multiple
      negative adjustment outcomes. Co-occurring symptomatology and CP demonstrated
      more stability and was associated with more severe adjustment problems than
      depressive symptoms over time. Categorical analyses suggested that, in terms of
      adjustment problems, youth with co-occurring symptomatology were generally no
      worse off than those with CP-alone, and those with depressive symptoms-alone were
      similar over time to those showing no symptomatology at all. Few gender
      differences were noted in the relations among CP, depressive symptoms, and
      adjustment over time.

PMID- 16967337
TI  - Effects of "dual focus" mutual aid on self-efficacy for recovery and quality of
      life.
AB  - Four million adults in the U.S. have co-occurring serious mental illness and a
      substance use disorder. Mutual aid can usefully complement treatment, but people
      with co-occurring disorders often encounter a lack of empathy and acceptance in
      traditional mutual aid groups. Double Trouble in Recovery (DTR) is a dual focus
      fellowship whose mission is to bring the benefits of mutual aid to persons with
      dual diagnoses. Three hundred and ten persons attending 24 DTR groups in New York
      City during 1998 were interviewed and followed-up for two years. A mediational
      model was specified and results across time were summarized with generalized
      estimating equations (GEE). Degree of DTR Affiliation (attendance and
      involvement) was significantly associated with Self-efficacy for Recovery and
      three quality of life measures: Leisure Time Activities, Feelings of Well-Being
      and Social Relationships. Self-efficacy fully mediated the effects of DTR
      Affiliation on Leisure Time and Feelings and partially mediated DTR's effect on
      Social Relationships. The association of DTR involvement with self-efficacy is
      consistent with the processes inherent in mutual aid, although the observational
      nature of these data preclude causal inference. To improve outcomes, clinicians
      should facilitate affiliation with dual focus groups among persons with dual
      diagnoses as part of a comprehensive treatment approach.

PMID- 16967338
TI  - Implementing a depression improvement intervention in five health care
      organizations: experience from the RESPECT-Depression trial.
AB  - A growing body of research provides strong evidence for the effectiveness of
      programs to improve the primary care of depression based on the chronic care
      model. At the same time these changes are difficult to sustain in their original
      research settings and more difficult to widely disseminate in primary care
      practice. The RESPECT-Depression trial tested an implementation and dissemination
      strategy by working through five community-based health care organizations (HCOs)
      to implement the Three Component Model (TCM) for improving depression care. This
      report describes the results of extensive interviews of project principals,
      health care program managers, depression care managers, and practicing primary
      care clinicians to understand the characteristics of organizations and the
      intervention components that were associated with implementation and
      dissemination of the TCM. In two of the organizations all 29 participating
      practices continued the TCM, while all 31 practices from the other three
      organizations did not. Successful continuation and dissemination appeared to be
      related to a broadly shared vision and commitment among all levels of the
      organization, clearly articulated by clinical leadership, for pursuing a
      systematic change strategy to improve chronic care that included, but extended
      beyond, depression, independent of clear evidence for cost-effectiveness of
      expanding depression management. Factors associated with inability to sustain the
      TCM included lack of a shared change strategy throughout the organization and
      inability to rationalize an economic model of depression care.

PMID- 16967339
TI  - Project IMPACT: a report on barriers and facilitators to sustainability.
AB  - Project IMPACT is a collaborative care intervention to assist older adults
      suffering from major depressive disorder or dysthymia. Qualitative research
      methods were used to determine the barriers and facilitators to sustaining IMPACT
      in a primary care setting. Strong evidence supports the program's sustainability,
      but considerable variation exists in continuation strategies and
      operationalization across sites. Sustainability depended on the organizations'
      support of collaborative care models, the availability of staff trained in the
      intervention, and funding. The intervention's success was the most important
      sustainability factor, as documented by outcome data and through the "real world"
      experience of treating patients with this intervention.

PMID- 16967341
TI  - A focused approach to assessing program fidelity.
AB  - The primary goals of the present study were 1) to explore the types and
      frequencies of adaptation reported by facilitators; 2) to document their reasons
      for making those adaptations; and 3) to propose an efficient approach to the
      study of prevention program fidelity based on interview data. We interviewed 42
      program facilitators involved in a large-scale dissemination about their
      implementation of a community-based prevention program. Interview questions
      addressed facilitators' attitudes about program fidelity and the various types of
      changes, deletions, and additions they made. Although nearly all facilitators
      reported that fidelity to program curriculum was important, most also reported
      adapting the program. The most frequent reason facilitators gave for adaptation
      was deleting or changing material because they ran out of time. We employed a
      method used in business and health care settings (the Pareto principle, or the
      "law of the vital few") to identify the minority (30%) of types of adaptation
      that accounted for a majority (70%) of all adaptations reported. Similarly, we
      identified the minority of reasons (25%) for adaptation that accounted for a
      majority (75%) of reasons reported. This approach helps to focus the assessment
      of fidelity on those adaptations that occur with high frequency, since low
      frequency events are unlikely to have a significant impact on large-scale
      outcomes. High-frequency adaptations can then be targeted to determine their
      effect on outcomes; to address in training; and to assess on an ongoing basis for
      continuous quality improvement.

PMID- 16967342
TI  - The impact of the built environment on children's school conduct grades: the role
      of diversity of use in a Hispanic neighborhood.
AB  - A population-based study examined the relationship between diversity of use of
      the built environment and teacher reports of children's grades. Diversity of use
      of the built environment (i.e., proportion of a block that is residential,
      institutional, commercial and vacant) was assessed for all 403 city blocks in
      East Little Havana, Miami-a Hispanic neighborhood. Cluster analysis identified
      three block-types, based on diversity of use: Residential, Mixed-Use, and
      Commercial. Cross-classified hierarchical linear modeling was used to examine the
      impact of diversity of use, school, gender, and year-in-school on academic and
      conduct grades for 2857 public school children who lived in these blocks.
      Contrary to popular belief, mixed-use blocks were associated with optimal
      outcomes. Specifically, follow-up analyses found that a youth living on a
      residential block had a 74% greater odds of being in the lowest 10% of conduct
      grades (conduct GPA <2.17) than a youth living on a mixed-use block. In fact, an
      analysis of the population attributable fraction suggests that if the risk
      associated with residential blocks could be reduced to the level of risk
      associated with mixed-use blocks, a 38% reduction in Conduct GPAs <2.17 could be
      achieved in the total population. These findings suggest that public policy
      targeting the built environment may be a mechanism for community-based
      interventions to enhance children's classroom conduct, and potentially related
      sequelae.

PMID- 16967343
TI  - Depressive symptomatology among HIV-positive women in the era of HAART: a stress
      and coping model.
AB  - OBJECTIVE: An enhanced stress and coping model was used to explain depression
      among HIV-positive women in healthcare and community settings where highly active
      anti-retroviral treatment (HAART) was commonplace. METHOD: HIV-infected women in
      four cities (N=978) were assessed, cross-sectionally, for mental and physical
      health, stress, social support, and other background factors. RESULTS: Self
      reported level of depressive symptomatology was high. Number of physical
      symptoms, illness intrusiveness, and perceived stress were positively associated
      with depressed mood, while coping self-efficacy and social support were
      negatively associated. Stress mediated the effect of health status on depression
      and coping self-efficacy mediated the effect of psychosocial resources on
      depression. Our enhanced stress and coping model accounted for 52% of variance in
      depressive symtpomatology. CONCLUSIONS: Interventions focused on improving coping
      self-efficacy, bolstering social supports, and decreasing stress in the lives of
      HIV-positive women may help to reduce the negative effects of HIV disease on
      mood.

PMID- 16967344
TI  - The impact of neuropsychological deficits on functional stroke outcomes.
AB  - This review examines the available literature on neuropsychological outcomes of
      stroke and the literature on the ability of specific areas of neuropsychological
      deficit to predict functional stroke outcome. The literature reviewed indicates
      that post-stroke deficits in executive function, memory, language, and speed of
      processing are common, with those identified as having progressive 'post-stroke
      dementia' presenting with a similar, though more impaired profile, with increased
      impairments particularly noted in the area of memory. It is clear that some
      aspects of neuropsychological functioning (e.g., presence of neglect, aphasia,
      anosognosia; and verbal memory and attention deficits) show promise as a means of
      predicting post-stroke functional outcomes. Examining the available literature,
      it becomes evident that there is a need for long-term, large scale (i.e.,
      population based) follow-up studies, evaluating likely long-term
      neuropsychological outcomes of stroke and their prognostic utility.

PMID- 16967345
TI  - Short-term memory deficits are not uniform in Down and Williams syndromes.
AB  - Neuropsychological investigation of the development of the mnesic function in
      mental retardation has primarily focused on evaluating short-term memory (STM).
      Studies have often documented a reduced verbal short-term memory span in
      individuals with mental retardation and with Down syndrome in particular,
      compared to groups of mental age-matched controls. However, recent evidence
      suggests that verbal short-term memory is not equally impaired in all individuals
      with mental retardation. Findings in children with Williams syndrome are
      particularly relevant in this regard. Also, data concerning STM for visual
      information suggest that visual-object and visual-spatial working memory may be
      differently compromised in people with mental retardation. In particular,
      individuals with Williams syndrome exhibit specific difficulties in visual
      spatial but not in visual-object working memory tasks compared to typically
      developing children matched for mental age. Instead, people with Down syndrome
      show reduced performance in both visual-spatial and visual-object tests. Taken
      together, these results reinforce the view that intellectual disability is not a
      unitary condition characterized by homogeneous slowness of cognitive development
      but a variety of conditions in which some cognitive functions may be more
      disrupted than others. The finding that the working memory deficit in individuals
      with Williams and Down syndrome may be qualitatively differentiated also supports
      the hypothesis that it is not simply a manifestation of general cognitive
      impairment but, rather, the expression of a specific deficit of a discrete
      cognitive ability.

PMID- 16967346
TI  - Semi-mechanistic pharmacodynamic modeling for degarelix, a novel gonadotropin
      releasing hormone (GnRH) blocker.
AB  - An integrated semi-mechanistic pharmacodynamic (PD) model describing the
      relationship between luteinizing hormone (LH) and testosterone (T) after short
      term administration of degarelix was developed. Data from three clinical studies
      involving, intravenous (IV) and subcutaneous (SC) dosing, in healthy male
      subjects were available. Degarelix pharmacokinetic (PK) data from all studies
      were modeled simultaneously. One intravenous study was used to develop the PD
      model and the two other studies (IV and SC dosing) were used to qualify the
      model. Degarelix PK follows a two-compartment model and exhibits flip-flop
      kinetics after subcutaneous dosing. Based on physiological mechanism, the
      gonadotropin releasing hormone (GnRH) time course was described using a pulsatile
      release model. A precursor-dependent pool model was used to describe the kinetics
      of LH in the pituitary and plasma compartment. In males, LH regulates T
      production in leydig cells. Degarelix inhibits the release of LH from the pool
      compartment to the plasma compartment leading to decreased T production. The
      plasma half-life of LH (2.6-3.3 hr) and T (2.7 hr) match well with the literature
      reports. The proposed PD model reasonably described the time course of LH and T
      including the LH rebound for short-term studies. The model predicted the time
      course of LH and T for the second IV and SC dosing studies very well. However,
      the long term simulations from the final model did not match with literature
      reports. A modification is suggested based on the physiological understanding of
      the system. The proposed novel modification to precursor models can be of general
      use for predicting long term responses.

PMID- 16967347
TI  - [Intracranial temperature measurements in brain death].
AB  - BACKGROUND AND PURPOSE: Intracranial temperature in many clinical situations can
      significantly differ from core trunk temperature. Little is known about
      temperature relations in these locations in brain death. MATERIAL AND METHODS:
      The oesophageal and rectal temperatures were monitored in 52 comatose (GCS score:
      3-9) patients after head trauma or haemorrhagic stroke. Brain temperature was
      recorded in 44 patients who had been treated surgically. In 8 patients treated
      conservatively only tympanic temperature was monitored. Signs of brain death
      appeared in 27 patients. RESULTS: In patients who were unconscious but without
      signs of brain death, the brain and trunk temperature run parallel in time, the
      former being somewhat higher than the latter. The tympanic temperature matched
      well the temperature of the brain. With brain death symptoms all core
      temperatures fell by 2 to 4 degrees C during 6 to 12 hours. Most notably, the
      decrease in brain temperature far exceeded that of trunk temperature. As a
      result, intracranial temperature established itself as the lowest temperature of
      the body, being 2 to 4 degrees C lower than core trunk temperature. Tympanic
      temperature fall was less prominent, thus it no more mirrored brain temperature.
      CONCLUSIONS: After brain death intracranial temperature dissociates from core
      trunk temperature and from the tympanic temperature. Brain temperature lower than
      arterial blood temperature is incompatible with ongoing brain metabolism. So such
      temperature relations might be specific to brain death.

PMID- 16967348
TI  - [The influence of vascular risk factors and white matter hyperintensities on the
      degree of motor impairment in Parkinson's disease].
AB  - BACKGROUND AND PURPOSE: The aim of the study was to assess the prevalence of
      vascular risk factors and white matter hyperintensities (WMH) in patients with
      Parkinson's disease (PD) and its impact on clinical features such as motor
      impairment. MATERIAL AND METHODS: 60 patients with PD [25 women and 35 men; mean
      age 68.4 (51-81) years, mean duration of disease 8.4 (1-27) years] with good
      response to L-Dopa were studied. Besides neurological examination, the degree of
      motor impairment was evaluated in all patients using UPDRS, Hoehn-Yahr, and
      Schwab-England scales. All patients underwent MRI to assess the degree of WMH
      using Age Related White Matter Changes (ARWMC) Wahlund scale. Moreover, the
      prevalence of classic vascular risk factors included arterial hypertension,
      diabetes mellitus t. 1 and 2; plasma cholesterol, cardiovascular diseases,
      alcohol abuse and smoking was assessed. RESULTS: Presence of at least one
      vascular risk factor was noted in 19 patients (31.7%). No significant differences
      were found between the groups of patients with and without vascular risk factors
      with regard to all clinical parameters and total ARWMC score. These factors did
      not differ between the groups of patients with more than 3 vascular risk factors
      and other patients. WMH (ARWMC > or =1) occurred in 33 patients (55%). No
      significant differences in all analysed clinical factors and the total number of
      vascular risk factors between the groups with (ARWMC > or =1) and without
      (ARWMC=0) WMH were found. The group of patients with at least one focus with
      score of 2 in the Wahlund scale did not differ significantly in all analysed
      clinical parameters from the rest of the patients. CONCLUSIONS: Our data suggest
      that the severity of WMH and incidence of vascular risk factors are not
      significantly related with the degree of motor disability in PD.

PMID- 16967349
TI  - [The usefulness of fused MRI and SPECT images for the voxel positioning in proton
      magnetic resonance spectroscopy and planning the biopsy of brain tumors:
      presentation of the method].
AB  - BACKGROUND AND PURPOSE: Progress in neurooncology suggests a need to combine
      information from anatomical-morphological and functional imaging in diagnosis and
      management. It is not always possible to establish a correct diagnosis using MRI
      imaging techniques alone, especially in the case of recurrent brain tumors. It is
      suggested that the results of different imaging techniques should be combined
      especially in these circumstances. The aim of this study was to evaluate the
      usefulness of fused post gadolinium MRI and single photon emission tomography
      (SPECT) images for planning 1H MRS. MATERIALS AND METHODS: 19 patients with a
      histopathological diagnosis of glial brain neoplasms were examined. SPECT was
      performed after i.v. administration of iodine-alpha-methyltyrozine (IMT). Fused
      SPECT and post Gd MR images were obtained on a peripheral console (Linux, PC),
      using a self developed technique. 1H MRS was performed on a 1.5 T scanner with
      the single voxel (SVS) technique using STEAM (TE 20 ms, TR 2000 ms) and (PRESS TE
      136 TR 2000 ms) sequences. RESULTS: 1H MRS with a volume of interest positioned
      in the most metabolically active areas on fused images, gave a more accurate
      diagnosis of tumor type and grade that was clinically relevant in 3 patients.
      CONCLUSIONS: The authors conclude that planning 1H MRS with the use of fused MRI
      and SPECT images improves the diagnosis.

PMID- 16967350
TI  - [Antiphospholipid antibodies in children with migraine].
AB  - BACKGROUND AND PURPOSE: There are only a few investigations in the literature,
      that address the occurrence and the role of anticardiolipin antibodies (aCL) in
      children with migraine. The results of those studies are often contradictory. The
      aim of the study was to determine if the values of aCL in children with migraine
      differ from the control group. We tried to assess whether the type of migraine
      (with aura or without aura) had the influence on those values. MATERIAL AND
      METHODS: Sixty patients (mean age: 10.9+/-3.3 years), including 30 children with
      migraine hospitalized from January 2000 to December 2003 in the Department of
      Developmental Neurology Medical University of Gdansk and 30 healthy children,
      were studied. The values of aCL in class IgA, IgM and IgG were assessed by the
      immunoenzymatic method (ELISA test). RESULTS: The values aCL in IgA and IgG class
      were significantly different between the migraineurs and control group. The mean
      value of aCL in patients with migraine was 8.7+/-1.27 U/ml, while in the control
      group--3.81+/-1.74 U/ml. The positive values of aCL in class IgG were found in 11
      (37%) children with migraine, and positive values of aCL in class IgM were noted
      in 6 (20%) cases in the same group. The type of migraine had no influence on the
      values of aCL. CONCLUSIONS: Children with migraine present with the higher values
      of aCL than the control group. The mean values of aCL were within the normal
      range, therefore their role in pathogenesis of migraine remains unclear. The
      further observation is needed to assess the reliable role of higher values of aCL
      in pathophysiology of vascular disorders.

PMID- 16967351
TI  - [Comparison of plasma concentrations of fibrinogen in patients with ischemic
      stroke due to large vessel disease and small vessel disease].
AB  - BACKGROUND AND PURPOSE: Hyperfibrinogenemia is a known cardiovascular risk
      factor, but its role as a risk factor for ischemic stroke remains controversial.
      Most studies on this topic did not consider the different etiologies of ischemic
      stroke. We designed this study to compare plasma fibrinogen concentrations in
      patients with acute ischemic stroke due to large vessel disease (LVD) or small
      vessel disease (SVD). MATERIAL AND METHODS: We studied 203 patients with acute
      ischemic stroke, including 107 patients with SVD and 96 subjects with LVD.
      Etiology of stroke was established according to the TOAST criteria, using
      computed tomography, ultrasonography of the carotid and vertebral arteries as
      well as echocardiography. The plasma concentration of fibrinogen was measured in
      venous blood samples drawn within 48 hours from the onset of stroke. RESULTS:
      Patients with LVD were more likely to be men and more likely to have ischemic
      heart disease. The median plasma concentration of fibrinogen was higher in
      patients with LVD [3.7 g/l (2.9-4.9 g/l)] than in patients with SVD [3.2 g/l (2.6
      3.8 g/l); p=0.0001]. Hyperfibrinogenemia (i.e. plasma fibrinogen concentration
      >3.5 g/l) occurred more frequently in patients with LVD (54.2%) than in patients
      with SVD (35.5%; p=0.008). CONCLUSIONS: Patients with ischemic stroke due to LVD
      have a higher concentration of plasma fibrinogen than patients with SVD, they
      also present more frequently with hyperfibrinogenemia. Further studies of risk
      factors for stroke should take into account various etiologies of ischemic
      stroke.

PMID- 16967352
TI  - [Reconstruction of the sellar floor in transsphenoidal surgery: our experience of
      818 patients].
AB  - BACKGROUND AND PURPOSE: Transsphenoidal microsurgery (TSS) is the method of
      choice for resection of most pituitary tumors. Postoperative cerebrospinal fluid
      rhinorrhea is one of the most frequent complications of TSS. Its incidence ranges
      from 1.3 to 9.6%. Failure to close a cerebrospinal fistula can result in life
      threatening complications e. g. meningitis or tension pneumocephalus. Therefore
      sellar closure has to be done properly certainly and has to be watertight. The
      aim of the study was to evaluate the results of reconstruction of the skull base
      after TSS with autologous material (fascia lata and fat or muscle). MATERIAL AND
      METHODS: Our operative experience of reconstruction of the sellar floor during
      transsphenoidal surgery is described. We report the well known method of the
      sellar closure using autologous tissue (fascia lata and fat or muscle). We did
      not use other materials e.g., fibrin glue, titanium mesh etc. This technique has
      been performed in 316 patients. RESULTS: The postoperative cerebrospinal fluid
      leakage occurred in 7 patients. Four of them underwent early reoperation. Three
      others were treated successfully with lumbar drainage. In another patient, a
      cerebrospinal fistula occurred during chronic pharmacotherapy of the giant PRL
      secreting adenoma. Transsphenoidal reconstruction of the skull base according to
      the described method was performed in that case. Lethal meningitis occurred in
      one patient in our group. CONCLUSION: In our opinion the described method of
      reconstruction of the sellar floor is easy, safe and very effective.

PMID- 16967353
TI  - [Aspirin resistance theory].
AB  - Acetylsalicylic acid is an effective antiplatelet drug for primary and secondary
      prevention of heart and brain vascular diseases. Analyses of trials including
      patients with atherosclerosis proved that vascular ischaemic events have been
      reduced by 25% and risk of vascular death has been reduced due to aspirin. The
      increasing number of reports about aspirin resistance (the failure of the
      compound to protect from an ischemic event despite regular intake of appropriate
      doses) is alarming. The purpose of this review is to present current opinions and
      results of investigations connected with this problem.

PMID- 16967354
TI  - Current status of percutaneous vertebral augmentation techniques for vertebral
      compression fractures.
AB  - Vertebral compression fracture (VCF) is a common and debilitating problem that
      occurs in patients with osteoporosis and osteolytic tumors. Standard conservative
      management with narcotic analgesics, bracing, and immobilization is often
      ineffective, and major reconstructive surgery is poorly tolerated by this frail
      patient population. The limitations of conventional treatments stimulated the
      development of minimally invasive, percutaneous vertebral augmentation
      techniques, including vertebroplasty and kyphoplasty, which have become
      established as safe and effective treatments for VCF. This report reviews the
      current status of vertebroplasty and kyphoplasty in the management of acute VCF.

PMID- 16967355
TI  - [Charcot-Marie-Tooth disorders: past, today and tomorrow].
AB  - Both intra- and interfamiliar variability of the clinical course of Charcot-Marie
      Tooth disorders (CMT) were reported in the descriptions of the CMT disease in the
      19th century. In the 1950s, it was shown that CMT disorders may be classified
      into two main groups i.e. CMT 1 and 2 on the basis of motor nerve conduction
      velocity in the motor fibers of the median nerve (MNCV=38 m/s). With the
      neuropathological studies in the 1960s, especially electron microscopy, a further
      enrichment of CMT classification was possible (hypomyelinating neuropathy, CMT
      with focally folded myelin). Thus, CMT classification based on EMG and
      neuropathological studies created an enormous opportunity to develop molecular
      genetics studies in CMT. Since early 1980s up to date, molecular genetic studies
      in CMT disorders resulted in a discovery of 30 genes. The new forms have been
      added to CMT classification on the basis of molecular DNA studies. In the "DNA
      era" in CMT genetic counseling in this group of disorders may be offered to the
      patients. Due to a possibility of delineating CMT patients on the basis of
      "genetic background", myological semiology and diagnostics may be improved. The
      access, costs and range of molecular DNA studies are still limited in CMT
      disorders. It seems possible that in the near future microarray DNA technology
      may revolutionize CMT diagnostics. The question whether and when gene therapy
      will be available in CMT remains to be answered, similar to other disorders with
      a genetic background.

PMID- 16967356
TI  - [Current possibilities of assessment of quality of life in multiple sclerosis].
AB  - An overall aim of treatment in multiple sclerosis is to minimize the negative
      impact of the disease on functioning and quality of life of patients. Therefore,
      a measurement of functioning and quality of life should be included in the
      evaluation of the effectiveness of treatment. In this paper, the most commonly
      used quality of life questionnaires, either generic or specific, are presented.
      The information about clinical and functional status are useful in the
      interpretation of the quality of life assessment results. Therefore, the
      instruments for the assessment of depression, cognitive functions, functional
      ability and fatigue in multiple sclerosis are also described.

PMID- 16967357
TI  - [Headache induced by oral intake of metoprolol in a patient with chronic and
      limited cardiac tamponade].
AB  - The papers describing the secondary headache attributed simultaneously to
      vascular disorder beyond the head and neck and use of drug are lacking. There is
      no adequate position for that type of headache in the current classification of
      headache, either. The case of secondary headache induced by metoprolol in a 57
      year-old patient with superior vena cava syndrome (SVCS) is reported. He suffered
      from chronic paroxysmal headache with accompanying rash and the superficial
      jugular veins were over-flown about 30 minutes after an intake of 25 mg of
      metoprolol. At the seventh day of hospital stay, the sudden death occurred.
      Postmortem examination showed the limited cardiac tamponade caused by aortal
      perforation and adhesive pericarditis SVCS produced by chronic, limited cardiac
      tamponade revealed after oral intake of metoprolol can be the cause of secondary
      headache that might be defined as "headache attributed to vascular disorder
      beyond the head and neck and related to medication for other indications".

PMID- 16967358
TI  - [Intrasellar arachnoid cyst. A case report and review of the literature].
AB  - Intrasellar arachnoid cyst (IAC) is a very rare pathological lesion occurring in
      5 of 1000 autopsy cases, and constitutes 9% of all arachnoid cysts. As a space
      occupying mass, IAC may cause headaches, visual disturbances, hypopituitarism,
      precocious puberty, and the "bobble-head doll" syndrome. The pathogenesis of IAC
      remains controversial. Magnetic resonance imaging (MRI) is the neurodiagnostic
      tool of choice to evaluate IAC. The authors presented a 38 year-old woman
      suffering from severe chronic headaches, dysmenorrhea, and visual disturbance.
      MRI revealed an intrasellar cystic lesion that had compressed the optic chiasma.
      Preoperative endocrinological assessment revealed hyperprolactinemia and
      hypogonadotropic hypogonadism. The patient underwent transsphenoidal surgery. The
      cyst membrane was opened and clear, serous fluid was evacuated. The postoperative
      course was complicated by CSF leakage, which was corrected by an autologous fat
      graft placement. Visual field defects improved immediately after surgery but a
      transient panhypopituitarism and diabetes insipidus occurred. Postoperative MRI
      revealed no recurrence of the lesion during the four-year follow-up.

PMID- 16967359
TI  - [Severe cardiovascular complications due to the pituitary adenoma with
      acromegaly. An interdisciplinary approach to the treatment. A case report].
AB  - Acromegaly reduces life expectancy and leads to 3-5-fold increase in mortality.
      The main causes are cardiovascular, pulmonary and enhanced prevalence of deaths
      from malignancy. Successful therapy ought to normalize GH, IGF-I secretion,
      remove the adenoma mass and its local pressure effects and preserve pituitary
      functions intact to improve systemic morbidity and normalize mortality. The
      primary therapy for most patients with acromegaly is still transsphenoidal
      adenomectomy. The authors present a 64-year-old woman with diagnosed GH-secreting
      pituitary macroadenoma suffering from severe coronary heart disease and diabetes
      mellitus. Somatostatin analogue therapy was ineffective in our patient. She was
      unfit for transsphenoidal adenomectomy. The patient was qualified for coronary
      artery bypass grafting after cardiological investigation. We have decided to
      carry out the bypass grafting and transsphenoidal adenomectomy during one
      anaesthesia. Both surgical procedures and postoperative time were uncomplicated.
      Our patient feels well and she is in outpatient follow-up.

PMID- 16967360
TI  - Dysphagia-gastroesophageal reflux complex: complications due to dysfunction of
      solitary tract nucleus-mediated vago-vagal reflex.
AB  - We report on the complication of gastroesophageal reflux (GER) in four patients
      with lower brainstem dysfunction. These patients suffered from perinatal
      asphyxia, cerebellar hemorrhage, or congenital dysphagia of unknown origin and
      showed facial nerve palsy, inspiratory stridor due to vocal cord paralysis,
      central sleep apnea, and dysphagia, in various combinations. Naso-intestinal tube
      feeding was introduced in all of the patients due to recurrent vomiting and
      aspiration pneumonia resulting from GER. T2-weighted magnetic resonance (MR)
      imaging revealed symmetrical high intensity lesions in the tegmentum of the lower
      pons and the medulla oblongata in two of the patients, and pontomedullary atrophy
      in another patient. In normal subjects, lower esophageal sphincter contraction is
      provoked by distension of the gastric wall, through a vago-vagal reflex. Since
      this reflex arc involves the solitary tract nucleus, where the swallowing center
      is located, the association of dysphagia and GER in the present patients is
      thought to result from the lesions in the tegmentum of medulla oblongata. We
      propose the term "dysphagia-GER complex" to describe the disturbed motility of
      the upper digestive tract due to lower brainstem involvement. In children with
      brainstem lesions, neurological assessment of GER is warranted, in addition to
      the examination of other signs of brainstem dysfunction, including dysphagia and
      respiratory disturbance.

PMID- 16967361
TI  - Leptomeningeal lymphoma in a child with acquired immune deficiency syndrome.
AB  - Primary non-Hodgkin lymphoma of the central nervous system is rare in pediatric
      AIDS patients. We report a seven-year-old HIV-infected boy, in stage C3 of the
      disease, who developed non-Hodgkin lymphoma in the central nervous system with a
      leptomeningeal location. The patient started with signs and symptoms of increased
      intracranial pressure, impaired consciousness and then became blind. The
      diagnosis was based on brain biopsy, immunophenotypic studies of B cells, and
      Epstein-Barr virus serology of the cerebrospinal fluid. The boy was treated with
      intrathecal and systemic chemotherapy. Fifteen months after diagnosis he had
      clinically improved, but he then relapsed with a thalamic tumor. He was treated
      with radiotherapy and he died four months later. In the present article, we
      discuss diagnostic difficulties, evolution, treatment, and the association of
      this neoplasm with the Epstein-Barr virus.

PMID- 16967362
TI  - Toxocara infection is not associated with viral or bacterial central nervous
      system infection in children.
AB  - BACKGROUND: Helminth infections with larvae that migrate through the tissues have
      been considered risk factors for CNS infections. OBJECTIVES: The present work was
      designed to investigate the prevalence of anti- TOXOCARA antibodies in the serum
      and/or in the cerebrospinal fluid (CSF) of children with infectious meningitis or
      meningoencephalitis and of a control group, without meningitis, admitted at the
      Children's Hospital NS Gloria, Vitoria, ES, Brazil. PATIENTS AND METHODS: After
      adsorption with ASCARIS LUMBRICOIDES antigen, serum and/or cerebrospinal fluid of
      381 inpatients (201 with meningitis and 180 without meningitis) were submitted to
      an ELISA IgG, for anti- TOXOCARA antibodies using secretion/excretion antigens of
      third stage larvae of T. CANIS. RESULTS: No significant differences between the
      meningitis and the control groups were observed in the frequencies of positive
      tests for anti- TOXOCARA antibodies in the serum or CSF (respectively for the
      meningitis and control group: 33/103 or 32 % and 52/152 or 34.2 % for the serum,
      p = 0.821; 48/184 or 26.1 % and 23/121 or 19.0 % for the CSF; p = 0.196.
      CONCLUSION: The results demonstrated that TOXOCARA infection, evaluated by
      detection of anti- TOXOCARA antibodies in serum or CSF, is not associated with
      viral or bacterial meningitis or meningoencephalitis in children in our country.

PMID- 16967363
TI  - Interleukin-10 high producer allele and ultrasound-defined periventricular white
      matter abnormalities in preterm infants: a preliminary study.
AB  - OBJECTIVES: Inflammation plays a role in prematurity, in neonatal disorders of
      the brain, lung, eye, bowel, and in developmental disability among preterm
      infants. We initiated a pilot study in preterm children to determine the
      prevalence of single nucleotide polymorphisms (SNPs) in the
      infection/inflammation-associated genes for interleukin (IL)-10 (- 1082 G/A), IL
      1beta (+ 3953 C/T), tumor necrosis factor (TNF)-alpha (- 308 G/A) and toll-like
      receptor 4 (TLR-4) (Asp299Gly) and whether these SNPs affect the risk for
      neonatal disorders. STUDY DESIGN: We genotyped 73 children >/= 2 years of age
      whose gestational age at birth was < 32 weeks, and explored the associations
      between genotypes and neonatal disorders and developmental status at age 2 +
      years. RESULTS: Infants homozygous for the high IL-10 producer - 1082 G-allele (n
      = 15) were significantly less likely to develop ultrasound-defined
      periventricular echodensities. A non-significant, but prominent, risk reduction
      for bronchopulmonary dysplasia, high-grade retinopathy, cerebral palsy, and
      developmental delay at age 2 + years was present. Polymorphisms in the IL-1beta,
      TNF-alpha, and TLR-4 genes were too infrequent in our pilot sample to allow for
      reasonable analysis. CONCLUSION: Infants homozygous for the IL-10 high producer -
      1082 G allele might be at reduced risk for prematurity-associated disorders.

PMID- 16967364
TI  - Acute flaccid paralysis as initial symptom in 4 patients with novel E1alpha
      mutations of the pyruvate dehydrogenase complex.
AB  - We report on 4 boys from 3 families presenting initially in infancy with an acute
      onset of flaccid tetraparesis and areflexia, resembling Guillain-Barre syndrome
      (GBS). However, the cerebrospinal fluid (CSF) protein was normal, while serum and
      CSF lactate were elevated. All patients had recurrent similar episodes, usually
      associated with infections. Brain MRI showed T (2) hyperintensities in the basal
      ganglia in two boys, in one of them at the first clinical presentation; the other
      one had a normal brain MRI during the first episode. A third boy had a normal MRI
      twice but an increased lactate peak in the basal ganglia in (1)H-MR spectroscopy.
      Motor nerve conduction velocities (NCV) were normal in all patients. Biochemical
      analyses of muscle tissue, performed in two patients, revealed a deficiency of
      the pyruvate dehydrogenase (PDH). Molecular genetic analysis of the X-chromosomal
      E1alpha subunit of PDH showed three new mutations in phylogenetically conserved
      areas of the protein: Glu358Lys in patient 1; Arg88Lys in patient 2 and 3
      (brothers); and Leu216Ser in patient 4. In conclusion, children with "atypical
      GBS" should be evaluated for a mitochondrial disorder, including pyruvate
      dehydrogenase deficiency, even after a first episode.

PMID- 16967365
TI  - Skeletal muscle ultrasonography in children with a dysfunction in the oxidative
      phosphorylation system.
AB  - OBJECTIVE: The aim of this prospective study was to investigate the diagnostic
      value of quantitative skeletal muscle ultrasonography in children suspected of
      having a mitochondrial disorder. METHODS: Muscle thickness and quantitatively
      determined echo intensity of four muscles were established in 53 children with
      symptoms indicative of a mitochondrial disorder. RESULTS: A sensitivity of 25 to
      46 % was found, depending on the chosen cut-off point (abnormal or borderline
      abnormal), with a specificity of 85 to 100 %. Except for one, all abnormal
      ultrasound scans were found in children over five years of age. Within the group
      of patients with a mitochondrial disorder, a significant correlation was found
      between muscle echo intensity and age (r = 0.38; p = 0.047). CONCLUSIONS: We
      conclude that skeletal muscle ultrasound can be of additional value in the
      diagnosis of children with suspected mitochondrial disorders, especially in
      children over five years of age. With its low sensitivity, it is not suitable for
      screening purposes. However, since all abnormal ultrasound scans were found in
      children with a mitochondrial disorder, and no significant correlation with the
      MDC score was found, muscle ultrasound can be used complementary to this scoring
      system to facilitate the decision-making in pursuing further invasive
      diagnostics.

PMID- 16967366
TI  - Sequential neurological examinations in infants with neonatal encephalopathy and
      low apgar scores: relationship with brain MRI.
AB  - OBJECTIVE: The aims of this study were to (a) describe the evolution of
      neurological signs after the neonatal period in infants with neonatal
      encephalopathy and abnormal outcome and (b) to establish the relationship between
      the evolution of neurological signs and patterns of lesions on brain MRI.
      PATIENTS: Fifteen children with low Apgar scores, abnormal neurological signs at
      the end of the neonatal period, and abnormal outcome were examined at 1 - 2
      weeks, 5 - 7 weeks, and 6 months. All the infants had at least one MRI scan
      performed in the neonatal period. RESULTS: All infants had persistent
      abnormalities on all examinations performed but the severity of neurological
      impairment was variable and was related to the pattern of brain lesions. Infants
      with severe basal ganglia and white matter lesions showed abnormal axial and limb
      tone, movements, and visual function on all the examinations and none achieved
      independent sitting. In infants with moderate basal ganglia lesions and/or severe
      white matter changes, visual function and feeding improved by 5 - 7 weeks and
      were still normal at 6 months while limb tone, which was reduced in the first
      weeks, appeared to be normal at 5 - 6 weeks but was found to be increased at 6
      months; all were able to sit unsupported at 2 years and most of them achieved the
      ability to walk with support. CONCLUSIONS: Our results suggest that the evolution
      of the neurological patterns after the neonatal period in infants with persisting
      neonatal abnormalities depends on their pattern of brain lesions.

PMID- 16967367
TI  - Aicardi syndrome: presentation at onset in Swedish children born in 1975-2002.
AB  - In a nation-wide survey of Aicardi syndrome, defined as the onset of epilepsy in
      the first six months of life, agenesis of the corpus callosum (partial or total)
      and lacunar chorioretinopathy, 18 patients, all girls, born between 1975 and 2002
      were identified in Sweden. Fifteen were definite cases and three were regarded as
      probable, since they only fulfilled two of three inclusion criteria in addition
      to other cerebral malformations and/or chorioretinal changes. Calculations based
      on this survey and population-based studies on epilepsy in retarded children
      yielded a prevalence rate in the range of 2 - 15 : 100 000 girls. All but one had
      an ordinary birth weight, length and head circumference for gestational age. One
      was born preterm, one post term. The age at diagnosis varied from three days to
      12 years and decreased during the period reflecting the increased awareness of
      the syndrome. Eleven came to medical attention because of seizures. Six had
      myoclonic, four generalized tonic-clonic and eight tonic, clonic or complex
      partial seizures. One had hypsarrhythmia, five multifocal epileptiform activity,
      three bilateral independent bursts, two burst-suppression pattern, six other
      types of spikes and one slowing of background activity. Asymmetrical EEG
      abnormalities indicating independent hemispheric dysfunction were detected in
      13/18 (72 %). Complete absence of the corpus callosum was found in 13/18 (72 %),
      although not identical with the previous group, a partial defect in 3/18 (17 %),
      and a thinning in 2/18 (11 %). Of 15 children with definite Aicardi syndrome, 13
      had binocular and two monocular lacunae. In one of the latter two, subtle
      monocular lacunae were found on fundus photographs, but had been missed on
      repeated clinical examinations. Of three children with probable Aicardi syndrome
      typical lacunae were reported in one and other kinds of depigmentation in the
      other two. Most of the children had anomalous optic discs. Neuroimaging in
      infancy or early childhood combined with ophthalmological examination and ocular
      fundus photography will facilitate an early diagnosis of Aicardi syndrome.
      Seizure type and EEG abnormalities may be non-specific at onset.

PMID- 16967368
TI  - Transient encephalopathy with reversible white matter lesions in children.
AB  - We report on two children with acute encephalopathy showing mild clinical
      manifestations and reversible white matter lesions. In both patients, MRI
      revealed high intensities on T (2)-weighted imaging and marked reductions of
      water diffusion in the white matter of the bilateral centrum semiovale and the
      corpus callosum. These abnormalities disappeared along with the neurological
      symptoms within a week in both patients. These children represent a
      characteristic group of patients among childhood acute encephalopathy.

PMID- 16967369
TI  - Acute neuronopathic Gaucher disease complicated by fatal gastrointestinal
      bleeding.
AB  - Gaucher disease, a rare lysosomal storage disease caused by deficiency of
      glucocerebrosidase, may present with gastrointestinal bleeding. We report about
      an 11-month-old boy suffering from acute neuronopathic Gaucher disease who died
      after massive gastrointestinal bleeding. A gastric ulcer was found as the sole
      bleeding source. The gastric mucosa showed marked infiltration with Gaucher
      cells, in particular around the ulcer. Alterations of the gastrointestinal mucosa
      offer a new explanation for gastrointestinal bleedings in this disease.

PMID- 16967370
TI  - Influenza a-associated acute necrotizing encephalopathy.
AB  - Acute inflammatory processes of the brain tissue and meninges caused by viruses
      are relatively common and may be caused by a number of different viral agents.
      The specific etiological agent is not identified in many instances. Most cases
      completely recover. The prognosis depends upon the severity of the clinical
      illness, the specific etiology, and the age of the child. Acute necrotizing
      encephalopathy (ANE) is an important clinical type of encephalitis. In recent
      years, many cases of ANE caused by influenza A virus infection have been reported
      from different Eastern and European countries. In this paper we describe a young
      child with influenza A-associated ANE.

PMID- 16967372
TI  - Lymphatic spread in resectable lung cancer: can we trust in a sentinel lymph
      node?
AB  - The aim of this study was to describe lymphatic spread in resected lung cancer
      patients and evaluate for the presence for a reliable sentinel lymph node.
      Onethousand and eighty-eight patients with NSCLC underwent resection. Twelve to
      sixteen percent of the patients with primaries in the upper lobes had an
      involvement in the upper mediastinum; in 12 %, it was subcarinal, in 6 % and 3 %,
      in the lower mediastinum at paraoesophageal and ligamentum pulmonale sites,
      respectively. The rate of "lymph node skipping" is between 31 and 74 %. An
      isolated involvement of mediastinal nodes is possible without involvement of the
      N-1 position. Irrespective of the location of the primary tumour, there is a high
      incidence of "lymph node skipping" because of the specific architecture of the
      pulmonary, hilar and medistinal lymph nodes. Therefore, a reliable sentinel lymph
      node in lung cancer cannot be defined. In conclusion, systematic lymph node
      dissection in anatomical compartments is the gold standard for evaluation of the
      exact pN stage. Furthermore, a complete R/O-resection is a prognostically
      relevant factor in the surgery of NSCLC.

PMID- 16967373
TI  - Differential gene expression in response to ventricular unloading in rat and
      human myocardium.
AB  - Left ventricular unloading by mechanical assist devices induces myocardial
      atrophy. We aimed to systematically identify differentially expressed genes in a
      model of physiological atrophy (unloading of healthy rat myocardium) and compare
      these changes to those in a unloaded, failing human heart. METHODS: Atrophy in
      rat hearts was induced by heterotopic transplantation of a donor heart into the
      abdomen of an isogenic recipient. After one week, donor and recipient RNA was
      isolated. Differential gene expression was assessed by subtractive hybridization.
      Two screens with radioactive probes were performed to verify differentially
      expressed clones. Positive clones were sequenced and cDNA of genes of known
      homology were used as probes for hybridization with RNA from separate atrophied
      rat hearts and human tissue from a normal, failing or failing and unloaded left
      ventricle. RESULTS: We picked 1880 clones from the subtractive hybridization
      procedure (940/940: forward/reverse runs assessing up- or down-regulation,
      respectively). The first screen verified 465/140 and the second screen verified
      67/30 clones. 24/23 clones were sequenced and 14/10 homologies to known genes
      were found. In the atrophied heart, respiratory chain and metabolic genes were
      down-regulated (NADH-DH, cytochrome c oxidase, acetyl-CoA synthetase, myoglobin)
      and cellular recognition and stress genes were up-regulated (MHC1 and 2, HSP70).
      In the human heart, cytochrome c oxidase, acetyl-CoA synthetase, and myoglobin
      expression was increased in the failing heart and returned to normal with
      unloading. Unloading also resulted in up-regulation of HSP70. CONCLUSIONS: The
      genetic responses of failing human and healthy rat myocardium to mechanical
      unloading show similarities that appear to be independent of species differences
      and/or underlying disease. Thus, heterotopic heart transplantation is a relevant
      model for investigating the mechanisms of mechanical unloading.

PMID- 16967374
TI  - Inhibition of carotis venous bypass graft disease by intraoperative nucleic acid
      based therapy in rabbits.
AB  - BACKGROUND: Bypass graft stenosis after venous revascularisation procedures is
      characterised by massive neointimal and vascular smooth muscle cell proliferation
      triggered via endothelin-1 synthesis in the vessel wall. Decoy
      oligodesoxynucleotides (ODN) against the transcription factor activator protein-1
      (AP-1) inhibits pre-pro-endothelin-1 expression. METHODS: In 20 rabbits, an end
      to-side jugular vein bypass to the carotid artery was performed: (group A) 8
      grafts were treated with consensus AP-1 decoy ODN, (group B) 8 with mutated
      control ODN and (group C) 4 received no treatment. Explantation,
      histomorphometric and immunohistochemical evaluation was performed after 28 days.
      RESULTS: Median intimal thickness of groups: (A) 28.3 microm, (B) 48.4 microm,
      (C) 71.1 microm. The decoy ODN-treated group showed a significant reduction of
      neointima formation ( P = 0.029) and a downregulation of the endothelin receptor.
      CONCLUSIONS: In this model, neointima formation was reduced by local transfection
      with consensus decoy ODN against AP-1. Endothelin A and B receptor expression is
      downregulated. Molecular target nucleic acid-based therapies seem to be a future
      means of overcoming neointima proliferation in pressure-induced venous graft
      failure. Intraoperative local application makes it easy to use in routine
      revascularisation procedures.

PMID- 16967375
TI  - The excor device - revival of an old system with excellent results.
AB  - OBJECTIVE: We report on our experience with the BerlinHeart Excor system in
      adults and paediatric patients who underwent placement of the mechanical support
      device under emergency conditions and demonstrate the exceptional advantages and
      the considerable versatility of the system. METHODS: Since 2003, 29 consecutive
      patients (25 adults and 4 infants) with ages ranging from 10 months to 54 years
      underwent implantation of an Excor system. Main underlying heart diseases in
      adults were acute myocardial infarction (n = 9), dilative cardiomyopathy (n = 6),
      acute myocarditis (n = 6), whereas most of the children suffered from dilative
      cardiomyopathy. Ten patients had undergone implantation of an extracorporeal
      membrane oxygenation system. RESULTS: In 26 cases, a left ventricular assist
      device (LVAD) was implanted, while 3 patients had biventricular support. The
      support interval of all patients surviving the perioperative period lasted from
      30 to 412 days, mean period of support until heart transplantation or
      explantation was 184 +/- 117 days. Severe complications were rare. CONCLUSION:
      The Excor paracorporeal mechanical support system is an excellent and highly
      versatile device for the support of patients of all ages and different types of
      underlying heart disease in the mid-term and long-term. The implant procedure and
      the perioperative management are simple, and complication rates are low.

PMID- 16967376
TI  - Morbidity and embolic potential of left atrial cardiac tumors.
AB  - BACKGROUND: The aim of the study was to correlate cardiac tumors with
      implantation site, embolic potential and long-term evolution in patients
      undergoing surgery. METHODS: From 1981 to 2004, 78 patients underwent surgery for
      cardiac tumors. 64 % were female, with a mean age of 44 years. 14 % had embolic
      episodes (91 % CVA). The sizes of the tumors ranged from 0.4 cm to 10 cm. The
      most frequent tumors were myxomas (70 %), papillary fibroelastomas and fibromas.
      The preferential location was the left atrium (72 %). Data were analyzed using
      chi (2) and Student's T-tests, and the Kaplan-Meyer method and curves were
      compared with the log-rank test. RESULTS: Hospital mortality was 6 % and 8.2 % in
      the follow-up period. Myxoma was predominantly found in the left atrium ( P <
      0.0001; OR = 12.8 and 4 - 41 95 % CI). Left atrial tumors showed less mortality (
      P = 0.1; OR = 3 and 0.7 - 11.6 95 % CI), with a lower mortality for myxomas ( P <
      0.001), fewer recurrences ( P = 0.03; OR = 8.7 and 0.8 - 89 95 % CI), and a
      greater embolic potential than in other locations ( P = 0.03 % OR = 0.7 and 0.6 -
      0.8 95 % CI). CONCLUSION: Left atrial tumors showed greater embolic potential,
      fewer recurrences and less mortality.

PMID- 16967377
TI  - The effects of a neutrophil elastase inhibitor on the postoperative respiratory
      failure of acute aortic dissection.
AB  - BACKGROUND: Postoperative respiratory failure is often encountered in patients
      suffering from acute aortic dissection (AAD) and is believed to be influenced by
      release of neutrophil elastase after cardiopulmonary bypass. Sivelestat is a
      specific neutrophil elastase inhibitor, and this study aims to evaluate the
      effects of sivelestat on postoperative respiratory failure due to AAD. METHODS
      AND RESULTS: Patients who were operated for AAD from January 2000 to April 2005
      and who had less than 300 mmHg initial postoperative PaO (2)/FiO (2) were
      investigated retrospectively and divided into two groups. Group 1 (n = 9)
      received intravenous administration of sivelestat immediately after the
      operation, while Group II (n = 9) received no sivelestat. There were no
      significant differences between Group I and II with respect to patients'
      characteristics or background (age, body weight, operating time, cardiopulmonary
      bypass time, amount of bleeding, preoperative WBC number and initial PaO (2)/FiO
      (2)). Though patients in Group I showed a subtle improvement in certain
      parameters such as PaO (2)/FiO (2), A-aDO (2) and respiratory index (RI) over a 3
      day observation period compared to those of Group II, there were no significant
      differences. Neither postoperative mechanical ventilation time nor ICU stay
      differed between Group I and II. However, Group I showed a significantly greater
      improvement in the ratio of RI to initial RI on the 3POD compared to that of
      Group II (61.6 +/- 44.2 % vs. 111.9 +/- 40.9 %, P = 0.02). CONCLUSION: Inhibiting
      the activity of the neutrophil elastase may attenuate the postoperative
      respiratory complications of patients with AAD.

PMID- 16967378
TI  - Primary closure of median sternotomy: a survey of all German surgical heart
      centers and a review of the literature concerning sternal closure technique.
AB  - BACKGROUND: Sternal instability and mediastinitis are rare but serious
      complications following cardiac surgery with median sternotomy. METHODS: This
      study presents the results of a questionnaire, which was sent to all 79 German
      surgical heart centers. The conventional sternal closure technique, the
      parameters considered to be risk factors for sternal instability, and the
      surgical strategy in the presence of risk factors were determined. In addition, a
      literature research with the key words "sternal closure technique" and "sternal
      dehiscence" was performed. RESULTS: Conventional closure of primary sternotomy is
      done using many different methods, most often with surgical steel sutures (87 %)
      passed trans/peristernally (64 %). An osteoporotic or fractured sternum (70 x),
      and obesity (31 x) were the most frequently cited risk factors. The preferred
      osteosynthetic procedure for patients with an increased risk for sternal
      instability was the method of Robicsek (48 x). CONCLUSION: There is no uniform
      osteosynthetic method for primary sternal closure and there is substantial
      variation in the perception of risk factors for sternal instability and possible
      surgical consequences among the surgical heart centers in Germany.

PMID- 16967379
TI  - The Eurotransplant High-Urgency Heart Transplantation Program: an option for
      patients in acute heart failure?
AB  - OBJECTIVE: The Eurotransplant High-Urgency (HU) Heart Transplantation Program
      allows urgent heart transplants to be carried out in rapidly deteriorating
      patients with acute-to-chronic heart failure on the elective waiting list. But do
      the results of HU heart transplantation justify performing primary heart
      transplantation in these critically ill patients and offer an acceptable outcome?
      METHODS: Between 2000 and 2004, 64 heart transplantations (HTx) (32 elective and
      32 HU-HTx) were performed in our department. After having been accepted in an
      auditing process based on HU criteria, intensive care patients in NYHA functional
      class IV (cardiac index 1.7 l/min/qm BS), in end-organ failure (creatinine 1.5
      mg/dl), and with catecholamine dependence (dobutamine 8 microg/kg/min), are given
      priority with respect to organ allocation, and their data were compared to data
      from elective patients from the same period. RESULTS: HU requests were accepted
      in 97 % of cases. Two requests were not accepted, and both patients with
      contraindications for assist device implantation died within one week. The HU
      patients were 100 % in NYHA class IV, 93 % of the elective patients were in NYHA
      class III. Waiting time on the HU list was 13 days, and 7 of these patients died
      before HTx. Following heart transplantation, survival rates at 30 days and at one
      year of the HU group were 88 % and 85 % versus 94 % and 93 % in the elective
      group. CONCLUSIONS: This study shows that end-stage heart failure patients in the
      HU program can be transplanted primarily with good results if an organ is
      available in time. We are still in the position where the HU program only manages
      the organ shortage; there are still too many patients on the waiting list who die
      before receiving a donor organ.

PMID- 16967380
TI  - Spread of malignant cells in the surgical margin with stapled excision of lung
      cancer: comparison of aggressive clump and less traumatic jaw closure type
      staplers.
AB  - BACKGROUND: During stapled excision of lung cancer tissue, malignant cells can
      spread in the surgical margin. Stapling methods can be classified as aggressive
      clumping (AC) and less traumatic jaw closing (LTJC) types, thus the ratio of
      malignant margins may differ between stapler types. METHODS: The malignant status
      of the stapled margin was retrospectively investigated in 112 cases using a
      cytology technique. Stapler type, maximum tumor diameter, distance from surgical
      margin, thoracotomy type, and tumor location were used as variables. In addition,
      clinical results of excision cases were assessed. RESULTS: The ratio of malignant
      margins was 22/54 (41 %) in the AC group and 11/58 (19 %) in the LTJC group ( P =
      0.01). Multivariate analysis revealed that the stapling method and tumor location
      were an independently significant factor. Surgical margin recurrence occurred
      only in 4 (57 %) of 7 cases with malignant margin. CONCLUSIONS: The AC type
      method showed a greater potential to spread malignant cells, thus there seems to
      be a higher possibility of regional relapse with that technique.

PMID- 16967381
TI  - Entrapment of guidewire in the coronary stent during percutaneous coronary
      intervention.
AB  - A 76-year-old man presented with chest discomfort. On coronary angiography,
      subtotal occlusion in the mid-right coronary artery (RCA) and 60 % tubular
      stenosis in the distal RCA were revealed. Two intracoronary stents could be
      placed in the RCA without any difficulty. However, the guidewire could not be
      removed. The intraoperative finding showed that the guidewire had become
      entrapped in the coronary stent. The guidewire was successfully removed and
      emergency coronary bypass grafting was performed.

PMID- 16967382
TI  - Repair of postinfarction ventricular septal defect through the right atrium.
AB  - Repair of post infarction posterior ventricular septal defect has generally been
      performed with a ventriculotomy through the infarcted zone. This approach has a
      significant mortality and morbidity due to haemorrhage, extension of infarction
      or further compromise of ventricular function secondary to suture placement. We
      present a case with delayed repair of a post infarction posterior septal defect
      using a right atrial approach, where no discrete infarct or other abnormality of
      the free ventricular wall was found.

PMID- 16967384
TI  - Pulmonary myofibroblastic pseudotumor: a rare surgical pathology.
AB  - Pulmonary myofibroblastic pseudotumors are rare surgical pathologies, of unknown
      origin, with benign behavior and a good prognosis if completely resected. We
      present a 21-year-old male with a solitary pulmonary nodule found during a
      routine chest X-ray with CT scan confirmation. After a 16-month follow-up, the
      nodule increased in size and the patient developed mild dyspnea. He underwent an
      elective left postero-lateral thoracotomy and excision of the mass with an upper
      lobectomy. Pathologic studies revealed a pulmonary myofibroblastic pseudotumor.

PMID- 16967383
TI  - Extra-anatomic management of homograft reinfection after thoracic aortic rupture.
AB  - Vascular graft infections involving the thoracic aorta have high morbidity and
      mortality rates. The management of homograft reinfection has not been discussed
      yet. A 23-year-old woman suffered a rupture of the descending thoracic aorta.
      Seven months after interposition of a Dacron graft she was readmitted for graft
      infection and a homograft was inserted. An esophageal lesion was oversewn. Follow
      up CT showed several aneurysms around the homograft. She underwent implantation
      of an extra-anatomic ascending-descending aorta Dacron bypass with stump closure
      of the descending aorta. The patient is alive and free from reinfection seven
      years later.

PMID- 16967385
TI  - Posttraumatic pulmonary pseudocyst: a rare complication of blunt chest trauma.
AB  - Posttraumatic pulmonary pseudocyst is a rare cavitary lesion lacking an
      epithelial lining, which develops within the pulmonary parenchyma after blunt
      chest trauma. Such pseudocysts develop most commonly in children and young
      adults. The clinical course is usually benign with spontaneous resolution of the
      radiologic manifestations within 2 to 4 months after trauma. A young male injured
      in a motor vehicle accident, sustaining a posttraumatic pulmonary pseudocyst, is
      presented here.

PMID- 16967386
TI  - Thymolipoma of the anterior mediastinum: videothoracoscopic removal using a
      bilateral approach.
AB  - Thymolipoma, a rare benign neoplasm of the anterior mediastinum, is often
      asymptomatic and as a result it can become quite large before it is diagnosed. CT
      is the most accurate diagnostic technique to identify the adipose tissue, but it
      often cannot make a differential diagnosis differentiating it from other anterior
      mediastinal masses; transthoracic biopsy also reveals the presence of fatty
      tissue, but a definitive diagnosis can only be achieved by means of surgical
      excision, which is also curative. We describe the case of a young woman who
      presented with a fatty neoplasm of the anterior mediastinum. The mass was removed
      using single-stage bilateral sequential videothoracoscopy. The histopathological
      diagnosis was thymolipoma.

PMID- 16967387
TI  - Large mediastinal sarcoma in a patient with Gorlin-Goltz syndrome.

PMID- 16967390
TI  - [Elevated concentrations of fecal calprotectin in patients with liver cirrhosis].
AB  - BACKGROUND AND OBJECTION: Bacterial translocation from the gut lumen is
      considered to play an important role in the development of infectious
      complications in patients with liver cirrhosis. This translocation might be
      increased by inflammation of the gut mucosa. Calprotectin is a cytoplasmatic
      protein of neutrophilic granulocytes and is an established marker for the
      assessment of localized intestinal inflammation. It was the aim of the current
      study to systematically evaluate a localized intestinal inflammation in patients
      with liver cirrhosis by means of fecal calprotectin concentrations. PATIENTS AND
      METHODS: Fecal calprotectin concentrations were determined in 53 consecutive
      patients with liver cirrhosis and in 18 subjects without intestinal or liver
      diseases, who were comparable with respect to age and gender. Patients with
      diarrhoea, inflammatory bowel disease and a positive stool test for occult blood
      were excluded from the study. Fecal calprotectin concentrations were measured by
      a sandwich ELISA. The systemic inflammatory reaction of the patients was assessed
      by C-reactive protein, white blood cells counts and the serum concentrations of
      the cytokines IL-6, IL-8 and IL-10. RESULTS: Fecal calprotectin concentrations
      were significantly increased in patients with liver cirrhosis (median 37.0 mg/kg)
      compared to controls patients (median 2.2, P < 0.0001). There were no significant
      correlations of calprotectin concentrations with systemic inflammatory
      parameters, like CRP, white blood cell count or serum cytokines. However, fecal
      calprotectin concentrations were significantly associated with the stage of liver
      cirrhosis as expressed by the Child-Pugh score ( P < 0.001). A trend towards
      higher concentrations of calprotectin was found in patients with alcoholic liver
      cirrhosis ( P = 0.1). CONCLUSIONS: Patients with liver cirrhosis display elevated
      fecal calprotectin concentrations as a potential sign of intestinal inflammation.
      Further studies are warranted to establish a role of calprotectin for the risk
      assessment of infectious complications secondary to bacterial translocation in
      patients with liver cirrhosis.

PMID- 16967391
TI  - [Retroperitoneal abscess in a man with severe necrotizing pancreatitis].
AB  - HISTORY AND ADMISSION FINDINGS: A 65-year-old man was admitted to the emergency
      unit of another hospital with severe acute abdominal pain. Medial laparotomy
      revealed a tear in the lower pole of the capsule of the enlarged spleen. Results
      of some laboratory tests became available only after the procedure: Lipase and
      amylase levels were markedly elevated at 5097 U/l (normal range < 100 U/l) and
      1776 U/l (normal range < 60 U/l), respectively. These findings suggested acute
      pancreatitis as cause of the acute abdominal pain. Conservative treatment was
      initiated, but because of progressive clinical deterioration with fever, dyspnea
      and tachyarrhythmia he was transferred to our hospital for further treatment.
      INVESTIGATIONS, DIAGNOSIS AND TREATMENT: Chest X-ray revealed bilateral pleural
      effusion. Contrast-enhanced abdominal CT scan revealed an acute peripancreatic
      fluid collection and extensive pancreatic necrosis extending into the perirenal
      space, hilum of the spleen and transverse mesocolon. Despite the placement of
      multiple percutaneous pigtail catheters clinical improvement of the severe
      necrotizing pancreatitis was only temporary and repeated episodes of fever and
      septicaemia occured. Supported by a multidisciplinary consensus an endoscopic
      ultrasound (EUS)-guided transgastric drainage of the pancreatic abscess was
      performed with placement of two double-pigtail catheters and a nasocystic drain
      for irrigation. After this intervention the patient}s condition rapidly improved,
      inflammatory parameters normalized and the retroperitoneal abscess gradually
      resolved. CONCLUSION: A multidisciplinary consensus and modern interventional
      approaches such as EUS-guided endoscopic therapy are mandatory to successfully
      approach severe necrotizing pancreatitis and its complications.

PMID- 16967393
TI  - [Multidisciplinary treatment of rectal cancer].

PMID- 16967394
TI  - [Visceral medicine: the gastroenterologist's point of view].

PMID- 16967395
TI  - [Visceral medicine: the surgeons's point of view].

PMID- 16967396
TI  - [Defensins: endogenous antibiotics as a central part of innate immunity].

PMID- 16967397
TI  - [Isolated ventricular non-compaction cardiomyopathy].

PMID- 16967399
TI  - The effect of intermittent nasogastric feeding on preventing aspiration pneumonia
      in ventilated critically ill patients.
AB  - This randomized, controlled study employed two feeding protocols for 107
      participants in two intensive care units (ICUs) of a medical center to
      investigate the efficacy of intermittent nasogastric (NG) feeding in preventing
      aspiration pneumonia in critically ill patients on ventilators. The participants
      were randomly assigned to receive continuous (51 patients) or intermittent (56
      patients) feeding. The primary outcomes, including gastric emptiness index and
      pulmonary aspiration index, were examined on Day 0 and Day 7 of the intervention.
      In addition, patients were followed up to the 21st day to evaluate the secondary
      outcomes, which included length of stay (LOS) in the ICU and airway status. The
      results showed that the patients in the intermittent feeding group had a higher
      total intake volume at Day 7 (p = .000), had been extubated earlier at Day 21 (p
      = .002), and had a lower risk of aspiration pneumonia (odds ratios: 0.146, 95% CI
      = 0.062-0.413, p = .000) than the patients in the control group. Participants
      being treated with a high dose of dopamine were 2.95 times more likely to get
      aspiration pneumonia than those receiving a low dose of dopamine (95 % CI = 1.076
      8.107, p = .035). However, there was no significant difference between the two
      groups'; LOS. The results of this study provide evidence that clinical caregivers
      may use to make better decisions in terms of feeding methods for critically ill
      patients.

PMID- 16967400
TI  - A comparison study of nursing care quality in different working status nursing
      staffs: An example of one local hospital.
AB  - To reduce costs, many hospitals are trying to adopt strategies to contract out
      their nursing workforce. The purpose of this study is to compare the quality of
      health care among the following three categories of nursing workforces in public
      hospitals: outsourced nurses, permanently employed nurses and contracted nurses
      compensated based on hours worked. The research sample included 300 patients
      cared for by 78 nurses in insurance wards in a local public hospital. Four
      methods were used to evaluate care quality. They included examining medical
      records, interviewing nurses, observing, and interviewing patients. The study
      found the best care quality was delivered by permanently employed nurses followed
      by that delivered by contracted nurses. The worst care quality was delivered by
      outsourced nurses employed by agency companies contracted to the public hospital.
      Care quality dimensions that were statistically significant among three
      categories of nurses included total quality of nursing care, nursing care
      planning, nursing instruction, and nursing evaluation.

PMID- 16967401
TI  - A comparison of massage effects on labor pain using the McGill Pain
      Questionnaire.
AB  - The purpose of this study was to describe the characteristics of pain during
      labor with and without massage. Sixty primiparas in labor were randomly assigned
      to either a massage or control group and tested using the self-reported Short
      Form McGill Pain Questionnaire (SF-MPQ) at 3 phases of cervical dilation: phase 1
      dilation (3-4 cm), phase 2 dilation (5-7 cm), and phase 3 dilation (8-10 cm). The
      massage group received standard nursing care and massage intervention, whereas
      the control group received standard nursing care only. The results of this study
      showed: (1) In both groups, as cervical dilation increased, there were
      significant increases in pain intensity as measured by SF-MPQ; (2) massage
      lessened pain intensity at phase 1 and phase 2, but there were no significant
      differences between the groups at phase 3; (3) the most frequently selected five
      sensory words chosen by both groups were similar at phases 1 and 2- (a) sore, (b)
      sharp, (c) heavy, (d) throbbing, and (e) cramping, while of the 4 affective
      classes, "fearful" and "tiring-exhausting" were the most used by participants to
      describe the affective dimension. The results of this study indicate that,
      although massage cannot change the characteristics of pain experienced by women
      in labor, it can effectively decrease labor pain intensity at phase 1 and phase 2
      of cervical dilation during labor. Nurses and caregivers could consider using
      massage to help laboring women through the labor pain.

PMID- 16967402
TI  - Comparisons of life images and end-of-life attitudes between the elderly in
      Taiwan and New Zealand.
AB  - Rapid advances in medical technology may in the near future make "natural" aging
      and old age diseases the main causes of human death in affluent societies (apart
      from accidents). When dealing with end of life issues, medical sociology will
      need to focus more on life and death in seniors. Understanding the attitudes of
      older persons toward life and death is important for both performing end-of-life
      medical care and in developing end-of-life policies. Descriptive bioethical
      analysis of attitudes in different cultures can aid a fuller understanding of the
      views inside each culture and the trajectories of conflict situations within each
      culture. In-depth interviews were conducted with 112 senior citizens in Taiwan
      and with 25 senior citizens in New Zealand. All interviews were transcribed
      verbatim; qualitative data analysis was used to examine people's views on life
      and death. Their images of life and end of life attitudes were compared. Analysis
      of the key concepts they mentioned revealed distinctive views in life attitudes
      between these two groups. However, in spite of differences in culture and
      traditions, most life and end-of-life attitudes among elderly people in the two
      groups were rather similar. According to these similarities, an interpretation of
      these values was made within a Confucian and Taoist framework that might be
      applicable to non-Eastern cultures as well.

PMID- 16967403
TI  - The self-empowerment process of primary caregivers: A study of caring for elderly
      with dementia.
AB  - The purpose of this qualitative research was to explore and develop the process
      of self-empowerment for primary caregivers responsible for caring for elderly
      with dementia. Nine primary caregivers who lived in northern Taiwan were
      interviewed through a theoretical sampling procedure. In-depth, face-to-face
      interviews were tape-recorded and transcribed verbatim. The grounded theory
      method was applied for analyzing data. The six main components that emerged in
      this model: "filial piety", "feeling of out of control", "inner awareness", "care
      ability", "emotion reconstruction", and "life management". This model starts from
      "filial piety" and "feeling of out of control," then evokes caregivers' "inner
      awareness". The inner awareness powerfully influences caregivers' "care ability",
      "emotion reconstruction" and "life management," which account for the three inner
      mechanism parts in their caregiving experience. Each part comprises three stages
      that are influenced by "inner awareness". The lower stage of each part supports
      the next higher stage. The same stages in all parts parallel one another, and
      influence each other by providing support or creating barriers. On the other
      side, competition between support and barriers from the outside environment
      determines the completion of this self-empowerment process. Results of this
      research extend the knowledge in understanding the psychological processes
      related to caring for elderly with dementia. The findings also provide readers a
      positive viewpoint on the caring experiences of primary caregivers of elderly
      with dementia.

PMID- 16967404
TI  - The efficacy of hyperbaric oxygen therapy in improving the quality of life in
      patients with problem wounds.
AB  - The unpredictable course followed by severe, chronic, non-healing wounds not only
      restricts the daily activities of affected patients, but also impairs their
      quality of life (QOL). Hyperbaric oxygen therapy (HBOT) treatment for such wounds
      elevates tissue oxygen content, increases cellular repair functions and the
      probability of wound healing, and improves the patient's QOL. This was a
      longitudinal, prospective study, and used a purposive sampling method. A total of
      15 patients receiving HBOT at a medical center were enrolled. Data were collected
      by questionnaire before and after HBOT. The questionnaire included basic patient
      characteristics, self-perceived wound severity, wound physiological indices, and
      a QOL scale. The overall QOL score of the subjects after HBOT was higher than
      before HBOT. After HBOT, there was a positive correlation between the QOL of
      patients with problem wounds and the scoring of the Strauss wound classification
      system. After HBOT, there was a negative correlation between the QOL of patients
      with problem wounds and their self-perceived severity of the wound. The results
      were then used to provide suggestions for nursing care and additional research
      directions in order to effectively assist patients with problem wounds receiving
      HBOT, with the goal of achieving an optimal QOL.

PMID- 16967405
TI  - Risk factors for musculoskeletal discomfort in nurses.
AB  - Although musculoskeletal problems are commonly reported among the working
      population, including nurses, the prevalence and risk factors for musculoskeletal
      discomfort in nurses have not been extensively studied in Taiwan. To understand
      the risk factors and prevalence of musculoskeletal discomfort in different body
      parts among nurses in Taiwan, we performed a cross-sectional study using a self
      administered questionnaire to collect data. A total of 5,269 (93%) nurses
      completed the questionnaire survey. Musculoskeletal discomfort was found to be
      prevalent in this group. In terms of location, the lower back was the most
      commonly reported site of discomfort, followed by lower legs, shoulders and neck.
      Considering limitation of motion as an indicator of musculoskeletal discomfort
      severity, the highest levels of prevalence were reported, respectively, in the
      lower back, shoulder, lower leg, and wrist. Numbness was most commonly reported
      in lower legs, hands, thighs, and lower back. Risk factors for pain in
      shoulders/neck included waist-bending and waist-twisting, while those for lower
      back pain included duration of standing, waist-bending, and weight-lifting. Risk
      factors for lower leg pain included duration of standing and weight-lifting.
      Musculoskeletal discomfort was prevalent among nurses (91.6%). Pain in different
      body parts was related to different ergonomic risk factors while at work, namely,
      bending and twisting of the waist, and standing for extended periods of time. The
      development and testing of interventions to minimize these risk factors is
      warranted in future studies.

PMID- 16967406
TI  - The job self-efficacy and job involvement of clinical nursing teachers.
AB  - This paper explored the present status of self-efficacy and job involvement of
      clinical nursing teachers and investigated the predictive power of teachers'
      personal background variables on such, as well as the relationship between self
      efficacy and job involvement. A total of 419 participants in the survey sample
      were chosen among clinical nursing teachers at 19 public and private institutes
      of technology and junior colleges in Taiwan in 2004. The self-developed
      structural questionnaire was categorized into three sections, including personal
      background data, job self-efficacy related to the clinical teaching inventory and
      job involvement related to clinical teaching inventory. Of the total 419
      questionnaires distributed for this cross-sectional survey, 266 valid copies were
      registered, at a recovery rate of 63%. Findings indicated that both the job self
      efficacy and job involvement of clinical nursing teachers are at a medium to high
      level and that significant differences exist in job self-efficacy and job
      involvement based on differences in age, marital status, teaching seniority,
      teacher qualifications, and job satisfaction. Second, samples have significantly
      different performance in self-efficacy due to differences in education level
      attained and the medical institution to which nursing teachers had been assigned.
      Self-efficacy and job involvement are significantly positively correlated. These
      results can serve as a reference for the cultivation of nursing teachers and
      reform of clinical nursing education in the future.

PMID- 16967407
TI  - Is the inherent imprecision of manual leukocyte differential counts acceptable
      for quantitative purposes?

PMID- 16967408
TI  - Developing formal training opportunities for clinical pathology residents at
      pharmaceutical and biotechnology companies and commercial diagnostic
      laboratories.

PMID- 16967409
TI  - Method comparison in the clinical laboratory.
AB  - Studies comparing a new method with an established method, to assess whether the
      new measurements are comparable with existing ones, are frequently conducted in
      clinical pathology laboratories. Assessment usually involves statistical analysis
      of paired results from the 2 methods to objectively investigate sources of
      analytical error (total, random, and systematic). In this review article, the
      types of errors that can be assessed in performing this task are described, and a
      general protocol for comparison of quantitative methods is recommended. The
      typical protocol has 9 steps: 1) state the purpose of the experiment, 2)
      establish a theoretical basis for the method comparison experiment, 3) become
      familiar with the new method, 4) obtain estimates of random error for both
      methods, 5) estimate the number of samples to be included in the method
      comparison experiment, 6) define acceptable difference between the 2 methods, 7)
      measure the patient samples, 8) analyze the data, and 9) judge acceptability. The
      protocol includes the essential investigations and decisions needed to
      objectively assess the overall analytical performance of a new method compared to
      a reference or established method. The choice of statistical methods and
      recommendations of decision criteria within the stages are discussed. Use of the
      protocol for decision-making is exemplified by the comparison of 2 methods for
      measuring alanine aminotransferase activity in serum from dogs. Finally, a
      protocol for comparing simpler semiquantitative methods with established methods
      that measure on a continuous scale is suggested.

PMID- 16967410
TI  - Serum alkaline phosphatase isoenzyme activities in canine malignant mammary
      neoplasms with and without osseous transformation.
AB  - BACKGROUND: Increased serum activity of total alkaline phosphatase (TALP) has
      been found in dogs with mammary neoplasms, especially malignant mixed tumors. We
      hypothesized that the bone isoenzyme of alkaline phosphatase (BALP), a specific
      indicator of osteoblastic activity and bone formation, may contribute to
      increased TALP in dogs with mammary neoplasms with osseous transformation.
      OBJECTIVE: The purpose of this study was to compare serum TALP, BALP, and other
      ALP isoenzyme activities in dogs with mammary malignant neoplasms with and
      without osseous transformation. METHODS: Twenty-one female dogs with malignant
      mammary neoplasms were compared with 21 clinically healthy, age-matched female
      control dogs. Physical, clinicopathologic (including preprandial and postprandial
      serum bile acids, ACTH stimulation, and low-dose dexamethasone suppression
      tests), radiographic, and ultrasonographic examinations were performed on all
      dogs with tumors to assess coexisting conditions. On the basis of histologic
      examination of excised tumors, dogs were further classified as having epithelial
      (n = 11) or mesenchymal/mixed (epithelial-mesenchymal) (n = 10) neoplasms, the
      latter of which had histologic and radiologic evidence of bone formation. Serum
      TALP, BALP, liver alkaline phosphatase (LALP), and corticosteroid-induced
      alkaline phosphatase (CALP) activities were measured using biochemical methods.
      RESULTS: Dogs with malignant mammary tumors had significantly higher (P < .05)
      median serum TALP (170 U/L), BALP (59 U/L), LALP (49 U/L), and CALP (24 U/L)
      activities, compared with control dogs (81, 32, 37, and 5 U/L, respectively).
      Significantly higher activities of BALP and LALP were found in dogs with
      epithelial neoplasms; whereas, only CALP activity was higher in dogs with
      mesenchymal/mixed neoplasms. There was no significant difference in TALP or
      isoenzyme activitities between epithelial and mesenchymal/mixed groups.
      CONCLUSION: BALP activity is increased in some dogs with malignant mammary tumors
      but does not account for the increase in TALP in dogs with neoplasms that have
      osseous transformation.

PMID- 16967411
TI  - Sex-based differences in plasma chemistry and cardiac marker test results in
      Siamese fighting fowl.
AB  - BACKGROUND: Variations in the results of plasma chemistry analysis as a function
      of sex have rarely been demonstrated in avian species. OBJECTIVE: The aim of the
      present study was to investigate sex-related differences in values for routine
      biochemical variables, including conventional muscle enzymes, and novel cardiac
      markers in female and male Siamese fighting fowl. METHODS: Plasma chemistry
      analytes and cardiac marker proteins (creatine kinase-MB and cardiac troponin T)
      were measured in 70 Siamese fighting fowl using automated chemistry and
      immunoassay analyzers. Data were compared by 2-tailed t tests between sexes, and
      Spearman rank correlation between conventional and novel cardiac markers.
      RESULTS: Male fowl had significantly higher uric acid concentration and gamma
      glutamyltransferase activity; whereas, female fowl had significantly higher total
      cholesterol, triglycerides, and calcium concentrations, and alkaline phosphatase
      activity. As compared with female fowl, the fighting cocks also had significantly
      higher plasma concentrations of creatine kinase-MB and cardiac troponin T.
      Significant correlations between cardiac troponin T, but not creatine kinase-MB,
      and the activities of conventional muscle enzymes (creatine kinase, aspartate
      aminotransferase and lactate dehydrogenase) were observed in male but not in
      female fowl. CONCLUSION: These results indicate that sex-specific differences
      exist for several biochemical parameters and cardiac marker proteins in fighting
      fowl, and that such differences should be considered in interpreting laboratory
      test results.

PMID- 16967412
TI  - Comparison of white blood cell differential percentages determined by the in
      house LaserCyte hematology analyzer and a manual method.
AB  - BACKGROUND: The LaserCyte hematology analyzer (IDEXX Laboratories, Chalfont St.
      Peter, Bucks, UK) is the first in-house laser-based single channel flow cytometer
      designed specifically for veterinary practice. The instrument provides a full
      hematologic analysis including a 5-part WBC differential (LC-diff%). We are
      unaware of published studies comparing LC-diff% results to those determined by
      other methods used in practice. OBJECTIVE: To compare LC-diff% results to those
      obtained by a manual differential cell count (M-diff%). METHODS: Eighty-six
      venous blood samples from 44 dogs and 42 cats were collected into EDTA tubes at
      the Forest Veterinary Centre (Epping, UK). Samples were analyzed using the
      LaserCyte within 1 hour of collection. Unstained blood smears were then posted to
      Langford Veterinary Diagnostics, University of Bristol, and stained with modified
      Wright's stain. One hundred-cell manual differential counts were performed by 2
      technicians and the mean percentage was calculated for each cell type. Data (LC
      diff% vs M-diff%) were analyzed using Wilcoxon signed rank tests, Deming
      regression, and Bland-Altman difference plots. RESULTS: Significant differences
      between methods were found for neutrophil and monocyte percentages in samples
      from dogs and cats and for eosinophil percentage in samples from cats.
      Correlations (r) (canine/feline) were .55/.72 for neutrophils, .76/.69 for
      lymphocytes, .05/.29 for monocytes and .60/.82 for eosinophils. Agreement between
      LC-diff% and Mdiff% results was poor in samples from both species. Bland-Altman
      plots revealed outliers in samples with atypical WBCs (1 cat), leukocytosis (2
      dogs, 9 cats), and leukopenia (16 dogs, 11 cats). The LaserCyte generated error
      flags in 28 of 86 (32.6%) samples, included 7 with leukopenia, 8 with
      lymphopenia, 7 with leukocytosis, 1 with anemia, and 1 with erythrocytosis. When
      results from these 28 samples were excluded, correlations from the remaining
      nonflagged results (canine/feline) were .63/.65 for neutrophils, .67/.65 for
      lymphocytes, .11/.33 for monocytes, and .63/.82 for eosinophils. CONCLUSION:
      Although use of a 100-cell (vs 200-cell) M-diff% may be a limitation of our
      study, good correlation between WBC differentials obtained using the LaserCyte
      and the manual method was achieved only for feline eosinophils.

PMID- 16967413
TI  - Evaluation of static telepathology in veterinary diagnostic cytology.
AB  - BACKGROUND: Telepathology is the process of diagnostic pathology performed on
      digital images viewed on a display screen rather than by conventional light
      microscopy with glass slides. At present, electronic mail (e-mail) attachment is
      the most common communication medium for telepathology, because it is relatively
      simple and incurs minimal cost. OBJECTIVE: Our objective was to test whether
      telediagnosis through Internet e-mail could be applied to veterinary diagnostic
      cytology. METHODS: Using 20 cytology cases, on which a consensus diagnosis was
      reached by 3 experienced pathologists, a total of 130 images were digitized and
      sent as e-mail attachments from the Unit of Anatomic Pathology of the Faculty of
      Veterinary Medicine of Naples to the Unit of Pathology of the Faculty of
      Veterinary Medicine of Messina, Italy. The images were reviewed at the Unit of
      Pathology of Messina, where the consulting pathologist formulated his diagnoses
      by visualizing the images on the monitor of a computer. The telediagnoses were
      compared with the consensus diagnoses and with the consulting pathologist's
      interpretation using conventional light microscopy at a later date. RESULTS: The
      median time to capture images was approximately 30 minutes for each case. The
      median time to make a telecytodiagnosis was a few seconds for each case. Overall,
      there was good agreement (85%) between the consensus diagnosis and the
      consultant's telediagnosis. In 100% of the cases there was agreement between the
      consulting pathologist's telediagnosis and conventional glass slide diagnosis.
      CONCLUSION: Telepathology by e-mail provides acceptable efficacy and a faster
      turnaround time than post and can be applied to veterinary diagnostic cytology.

PMID- 16967414
TI  - Separation of serum glycated proteins by agarose gel electrophoresis and
      nitroblue tetrazolium staining in diabetic and normal cats.
AB  - BACKGROUND: The total glycated protein (fructosamine) concentration in serum
      consists mainly of glycated albumin and lipoproteins. Measurement of fructosamine
      is used to diagnose and monitor diabetes mellitus in cats. OBJECTIVE: The aims of
      this study were to measure glycated proteins in diabetic and healthy
      (nondiabetic) cats using a semiquantitative technique and to determine whether
      measurement of any of the fractions of glycated protein could be potentially
      advantageous for the diagnosis and monitoring of diabetic cats. METHODS: Serum
      samples from 6 cats with diabetes mellitus and 10 clinically healthy adult cats
      were assayed for total glycated protein using a nitroblue tetrazolium (NBT)
      fructosamine assay. Serum proteins were separated by agarose gel electrophoresis
      and stained with NBT to identify individual glycated proteins within the bands.
      Gels were scanned by densitometry at 525 nm and the glycated protein content was
      calculated with reference to the total glycated protein content of the sample.
      RESULTS: Diabetic cats with increased total fructosamine concentrations had
      higher concentrations of glycated albumin and glycated alpha- and beta
      lipoproteins compared with healthy cats. The concentration of glycated proteins
      in each of the fractions had a positive linear association with the total
      glycated protein content of serum, but there was large variation in the relative
      contributions of the 3 protein fractions to the total glycated protein
      concentration. CONCLUSIONS: Based on the results of this study, measurement of
      individual glycated fractions does not seem to offer any potential diagnostic
      advantage over measurement of total glycated protein (fructosamine) concentration
      alone. In some diabetic and healthy cats, glycated lipoproteins formed the major
      part of the total glycated protein, whereas in other cats albumin was the major
      contributor.

PMID- 16967415
TI  - Bone marrow mastocytosis in dogs with myelosuppressive monocytic ehrlichiosis
      (Ehrlichia canis): a retrospective study.
AB  - BACKGROUND: Bone marrow mastocytosis has been reported rarely in naturally
      occurring canine monocytic ehrlichiosis (CME). OBJECTIVES: The aims of the
      present study were to estimate the prevalence and magnitude of bone marrow
      mastocytosis in a case series of dogs with natural CME and to assess the
      association, if any, between mastocytosis and the clinical severity of the
      disease. METHODS: Seventy-six dogs with confirmed CME (Ehrlichia canis) were
      included in the study. Affected dogs were allocated into group A (n = 51) without
      bone marrow hypoplasia and group B (n = 25) with bone marrow hypoplasia. Twenty
      clinically healthy Beagles not previously exposed to E canis served as controls
      (group C). The main inclusion criteria for group A were documentation of
      normocellular to hypercellular bone marrow and complete clinical cure following a
      4-week treatment with doxycycline, while those for group B were bone marrow
      hypoplasia and lack of response to doxycycline. Bone marrow aspirate smears from
      all 96 dogs were Giemsa-stained and examined for the presence of mast cells,
      which were calculated as a percentage of 1,000 nucleated cells (NCs). The
      prevalence of mastocytosis was compared among the 3 groups by the Pearson's chi
      square test. RESULTS: Bone marrow mastocytosis (>0.1% of NCs) was found in 5
      (20%) dogs in group B (range, 0.5-2.5% of NCs; median, 1% of NCs). One dog in
      each of groups A and C had 0.1% mast cells in the marrow. The prevalence of bone
      marrow mastocytosis in dogs in group B was significantly higher (P = .004) than
      in groups A and C. CONCLUSION: Bone marrow mastocytosis can be seen in a
      substantial number of dogs with E canis-induced myelosuppression.

PMID- 16967416
TI  - Cerebrospinal fluid analysis and magnetic resonance imaging in the diagnosis of
      neurologic disease in dogs: a retrospective study.
AB  - BACKGROUND: Diagnosis of central nervous system (CNS) abnormalities in dogs can
      be challenging antemortem. Historically, cerebrospinal fluid (CSF) analysis has
      been used for routine diagnostic evaluation of animals with suspected neurologic
      disease; however, with increasing availability of magnetic resonance (MR)
      imaging, the need for concurrent CSF analysis may be questioned. OBJECTIVE: The
      purpose of this study was to retrospectively assess and compare the diagnostic
      information contributed from MR imaging and CSF analysis in a population of dogs
      presenting with neurologic disease. METHODS: Results of concurrent MR imaging and
      CSF analysis were evaluated in dogs presented for neurologic diseases. Based on
      clinical diagnosis, the sensitivity of CSF analysis and MR imaging for detecting
      a nervous system abnormality was calculated. Dogs with diagnoses confirmed by
      other diagnostic modalities were also evaluated separately. RESULTS: A total of
      256 dogs were included in the study. For clinical diagnoses in which
      abnormalities were expected, MR imaging abnormalities were found in 89% and CSF
      abnormalities in 75% of dogs; CSF abnormalities were more common than MR imaging
      abnormalities only in inflammatory CNS disease. The majority of CSF abnormalities
      were nonspecific; an etiologic diagnosis was determined in only 2% of CSF
      samples. MR imaging excelled in detecting structural disorders, revealing 98% of
      vertebral abnormalities. In confirmed cases (n = 55), 76% of MR images and 9% of
      CSF samples were diagnostic. When intervertebral disk disease (IVDD) and
      vertebral malformation were excluded from analysis (n = 16 remaining), 25% of MR
      images and 6% of CSF cytology results were highly indicative of the confirmed
      diagnoses; CSF titer results provided the diagnosis in 25% of these cases.
      CONCLUSION: CSF analysis may not be necessary when MR findings of IVDD or
      vertebral malformation/instability are obvious; however, when the cause of
      neurologic disorder is uncertain, concurrent MR imaging and CSF analysis provides
      the greatest assistance in establishing a clinical diagnosis.

PMID- 16967417
TI  - Biochemical and hematologic values for 18 clinically healthy radiated tortoises
      (Geochelone radiata) on St Catherines Island, Georgia.
AB  - BACKGROUND: The radiated tortoise (Geochelone radiata) is a critically endangered
      species in its native land, the southern portion of the island of Madagascar.
      Captive breeding programs have generated data on the breeding behavior and
      ecology of G radiata; however, hematologic and biochemical data also are
      critically important in managing populations. OBJECTIVE: The purpose of this
      study was to evaluate sex and seasonal effects on hematologic and biochemical
      data from captive radiated tortoises. METHODS: Whole blood was collected in
      January and August 2001 from 18 radiated tortoises (10 male, 8 female) housed at
      the Wildlife Survival Center on St Catherines Island, Georgia, as part of a
      routine health assessment. Routine hematologic and plasma biochemical analyses
      and electrophoresis were done using standard methods. Data from male and female
      tortoises were compared within and between seasons using 2-way ANOVA. RESULTS:
      RBC and HCT values were significantly higher in summer than in winter and were
      higher in males than in females. Total protein concentration did not differ
      significantly between males and females; however, female tortoises had
      significantly higher concentrations of alpha1- and beta-globulins in winter and
      summer compared to males. Male tortoises had significantly higher sodium and uric
      acid concentrations and LDH activity during winter, and higher urea concentration
      and LDH and CK activities in summer, compared with females. Female tortoises had
      significantly higher triglyceride and phosphorus concentrations in winter, and
      higher phosphorus, cholesterol, and triglyceride concentrations in summer,
      compared with males. CONCLUSION: Sex and seasonal differences in hematologic and
      biochemical values for radiated tortoises likely reflect vitellogenesis and egg
      production in females, and altered hydration status and activity in summer. Data
      from the tortoises in this study will be useful for the seasonal health
      assessment of this species.

PMID- 16967418
TI  - Cytologic analysis of synovial fluid in clinically normal tarsal joints of young
      camels (Camelus dromedarius).
AB  - BACKGROUND: Camels are important in the racing industry and for milk, meat, and
      hair production in the Middle East. Evaluation of synovial fluid is an important
      part of the assessment of musculoskeletal injuries in this species. Information
      in the literature regarding synovial fluid in camels is limited. OBJECTIVES: The
      objective of this study was to determine the protein and cellular composition of
      synovial fluid from the tarsal joints of clinically normal, young camels (Camelus
      dromedarius). METHODS: Thirty clinically healthy, male camels, aged 9 to 12
      months, were used in the study. Synovial fluid samples were collected from the
      right and left tarsal joints. Samples were processed within 60 minutes after
      collection. Total nucleated cell counts (TNCC) were assessed using a
      hemacytometer. Total protein concentration was determined using a refractometer.
      RESULTS: Forty-six samples were analyzed. The TNCC (mean +/- SD) was 175.8 +/-
      136.7 cells/microL (range 50-678 cells/microL). Differential cell percentages
      were obtained for lymphocytes (58.2 +/- 21.55%, range 15-90%),
      monocyte/macrophages (38.3 +/- 20.8%, range 10-85%), and neutrophils (3.5 +/-
      5.1%, range 0-15%). Protein concentration was 2.1 +/- 0.6 g/dL (range 1-3 g/dL).
      Significant differences were not observed in any parameters between right and
      left tarsal joints. CONCLUSION: Synovial fluid reference values were established
      and may be useful in the clinical investigation of joint disease in young camels.

PMID- 16967419
TI  - "Carry-on" dermal baggage: a nodule from a dog. Pyogranulomatous inflammation
      with intralesional fungal agents.
AB  - A 2-year-old intact female Australian Cattle Dog presented with a 1-cm diameter
      nonexudative dermal nodule on the medial aspect of the right thigh. Fine-needle
      aspiration revealed pyogranulomatous inflammation and many ovoid, 2-4 microm
      diameter, thin-capsulated, basophilic bodies that appeared to be fungal spores or
      yeast. Results of CBC, serum chemistry panel, lymph node palpation, and
      radiographs were unremarkable. Excisional biopsy and histopathology revealed
      pyogranulomatous folliculitis, furunculosis, and perifolliculitis. Rare fungal
      hyphae and spore forms were intimately associated with, and occasionally within,
      hair shafts. A morphologic diagnosis of dermatophytosis was made and Microsporum
      canis infection was confirmed by fungal culture. M canis is a common infectious
      agent found within the follicles and superficial keratin layers of canine skin.
      The kerion-type clinical presentation observed in the dog of this case is
      uncommonly observed with M canis. Additionally, the cytologic finding of multiple
      arthroconidia without hyphae is unusual. In the absence of hyphae, M canis
      arthroconidia may be confused with other fungal yeast bodies; therefore close
      scrutiny of a cytologic sample for arthroconidia associated with keratin, hair
      fragments, or hyphal structures is recommended.

PMID- 16967420
TI  - Serum lipid and lipoprotein parameters of Turkman horses.
AB  - BACKGROUND: Lipid transport systems in animals have been evaluated both as
      experimental models for lipid and lipoprotein metabolism in humans and to gain
      insight into the lipid metabolism of specific breeds. The Turkman horse is a pure
      blooded horse that lives on the margins of the Caspian Basin; information about
      serum lipids and lipoproteins in this breed is lacking. OBJECTIVE: The purpose of
      this study was to evaluate serum lipid and lipoprotein concentrations in
      clinically healthy Turkman horses. METHODS: Concentrations of triglyceride (TG),
      total cholesterol (TC), high density lipoprotein cholesterol (HDLC), low density
      lipoprotein cholesterol (LDL-C), and very low density lipoprotein cholesterol
      (VLDL-C), and lipoprotein electrophoretic patterns were determined in serum
      samples from 48 Turkman horses of both sexes and 0-12 years of age. Results were
      analyzed by 1-way ANOVA. RESULTS: In both sexes and all age groups, the relative
      percentages of LDL-C (44.2-64.3%) were higher than those of HDL-C (29.7-47.1%)
      and VLDL-C (5.9-9.0%). Serum concentrations of TG and TC were significantly
      higher in male (0.45 +/- 0.12 mmol/L; 2.70 +/- 0.45 mmol/L) than in female (0.34
      +/- 0.1 mmol/L; 2.15 +/- 0.3 mmol/L) horses in most age groups. The relative
      percentages of alpha- and beta-lipoproteins in electrophoretic tracings were
      62.77 +/- 5.05% and 36.67 +/- 4.29%, respectively. CONCLUSION: Serum lipid and
      lipoprotein values in Turkman horses differ from those of other equine breeds,
      and may be useful for evaluating metabolic diseases in this species.

PMID- 16967421
TI  - A femorotibial joint swelling with popliteal lymph node enlargement in a
      Rottweiler.
AB  - A 9-year-old male Rottweiler was presented to the Veterinary Medical Hospital
      Montenegro, Porto, Portugal with a large mass medial to the left stifle and
      radiographic signs of bone lysis involving the proximal tibia, fibula, and distal
      femur. A fine-needle aspiration was obtained from left popliteal lymph node,
      which was markedly enlarged. Cytologic examination revealed a highly cellular
      sample consisting of pleomorphic cells with marked anisocytosis and anisokaryosis
      and other criteria of malignancy. Some cells contained intracytoplasmic,
      granular, dark brown material, consistent with hemosiderin. Histologic evaluation
      of the surgically-excised lymph node revealed a neoplastic proliferation of
      histiocytic cells, with marked pleomorphism; occasional cells were
      erythrophagocytic. Mitotic figures were frequently observed, and many were
      atypical. Histologic findings were consistent with malignant histiocytosis.
      Necropsy examination confirmed the diagnosis of malignant histiocytosis with
      systemic involvement affecting most organs examined. This case of malignant
      histiocytosis case had an atypical clinical presentation, mimicking a
      musculoskeletal disorder. It underlines the importance of cytology as a simple,
      inexpensive, rapid and noninvasive complementary exam in routine clinical
      practice that can permit early diagnosis of the disease and timely selection of
      the most adequate therapy.

PMID- 16967422
TI  - Effect of repeated freeze-thaw cycles on routine plasma biochemical constituents
      in canine plasma.
AB  - BACKGROUND: The effect of repeated freeze-thaw cycles on plasma constituents has
      not been assessed in dogs, although such a procedure is not uncommon to use in
      routine laboratory practice. OBJECTIVE: To assess the effect of freeze-thaw
      cycles on routine plasma constituents in healthy dogs. METHODS: Six healthy adult
      dogs were used. Blood was sampled and placed in heparinized tubes. After
      centrifugation, plasma was separated into 5 aliquots. One aliquot was considered
      as the reference aliquot and used immediately for the assay of all of the
      biochemical constituents. All of the other aliquots were stored at 20 degrees C.
      Three aliquots underwent 1, 2, or 3 freeze-thaw cycles during a 1- to 3-day
      period. The last aliquot remained at 20 degrees C throughout the study and was
      thawed on the third day. The following biochemical constituents were assayed:
      glucose, urea, creatinine, total proteins, sodium, potassium, chloride, calcium,
      phosphates, aspartate aminotransferase (AST), alanine aminotransferase (ALT),
      creatine kinase (CK), and alkaline phosphatase (ALP). RESULTS: No clinically
      relevant change was observed between the different aliquots for all of the
      constituents. CONCLUSION: Repeated freeze-thaw cycles do not cause changes in the
      biochemical constituents studied in canine plasma.

PMID- 16967423
TI  - Reluctant to dive: coelomic effusion in a frog.
AB  - An adult female, albino South African Clawed frog (Xenopus laevis) from a
      research colony at the Biological Resources Facility of the College of
      Agriculture and Life Sciences at North Carolina State University (NCSU) was
      presented with depression, lethargy, loss of diving reflex, and a distended
      abdomen. Cytologic examination of coelomic effusion fluid at the NCSU veterinary
      teaching hospital revealed a mixed population of inflammatory cells, including
      heterophils and a predominance of large mononuclear cells (macrophages) that
      often contained intracytoplasmic, negatively-stained, rod-shaped to filamentous
      organisms consistent with Mycobacterium sp. Ziehl-Neelsen stain revealed bright
      pink to red, acid-fast organisms with a beaded appearance. Histopathologic
      findings in tissues obtained at necropsy included marked, multifocal to
      coalescing, heterophilic, granulomatous and fibrinous coelomitis as well as
      severe multifocal heterophilic and granulomatous hepatitis, interstitial
      pneumonia and sinusitis/rhinitis. Slender gram-positive, acid-fast bacterial rods
      were identified in sections of coelomic pleura, kidneys, nasal cavities, spleen,
      liver, and pulmonary interstitium, indicative of systemic mycobacteriosis. Based
      on mycobacterial culture, the organism was identified as M marinum complex.
      Mycobacteria are variably gram-positive, often acid-fast, small rods that are
      ubiquitous in aquatic environments. The clinical and pathologic spectrum of
      disease in amphibians depends on host and pathogen status. Xenopus sp and several
      other frogs are good models for studying the pathogenesis of M tuberculosis
      infection. In addition to culture, polymerase chain reaction assays may be used
      for definitive identification of the organisms; accurate speciation may require
      further genetic investigation.

PMID- 16967424
TI  - Intracellular success: cytologic findings in an ulcerated submandibular mass from
      a cat.
AB  - A 1-year-old neutered male domestic shorthair cat had an ulcerated, proliferative
      lesion in the submandibular area that did not respond to antibiotic therapy.
      Impression smears from the mass revealed septic pyogranulomatous inflammation,
      with large numbers of pleomorphic bacteria observed intracellularly within
      macrophages as well as neutrophils. Bacterial culture was consistent with a
      diagnosis of Rhodococcus equi, a facultative intracellular coccobacillus capable
      of replicating within macrophages. The cat's lesion resolved after treatment with
      rifampin and clarithromycin. R equi should be considered as a differential
      diagnosis when coccobacilli are recognized within macrophages in cytologic
      samples.

PMID- 16967425
TI  - Cytologic identification of immature endospores in a dog with rhinosporidiosis.
AB  - An 8-year-old, intact, male Labrador Retriever was presented to the Boren
      Veterinary Medical Teaching Hospital at Oklahoma State University with a 2-month
      history of severe sneezing episodes that resulted in epistaxis and bilateral
      sanguineous discharge. Rhinoscopy revealed a small polypoid mass, and specimens
      were obtained for histopathology. Microscopic examination of formalin-fixed
      tissue specimens revealed organisms consistent with Rhinosporidium seeberi. The
      mass was surgically excised and impression smears were made for cytology
      examination. Smears revealed high numbers of endospores, typical of those
      previously described for R seeberi. In addition, numerous smaller structures,
      presumed to be immature endospores, were noted. The immature endospores were
      morphologically distinct from mature endospores and have not been described
      previously. Recognition of immature forms of Rhinosporidium may help prevent
      misidentification of the organism or misdiagnosis of a dual infection.

PMID- 16967426
TI  - Fatal hepatic sarcocystosis in a puppy with eosinophilia and eosinophilic
      peritoneal effusion.
AB  - A 3-month-old male Golden Retriever puppy was evaluated for lethargy and fever of
      2-days duration. Results of a CBC and biochemical profile revealed marked
      eosinophilia (6.3 X 10(3)/microL; reference interval 0.1-1.2 X 10(3)/microL),
      moderate thrombocytopenia, and increased activities of alanine aminotransferase,
      aspartate aminotransferase, and creatine kinase. Hepatomegaly and peritoneal
      effusion were found using abdominal ultrasound. Peritoneal fluid analysis
      revealed eosinophilic inflammation (23,000 nucleated cells/microL with 88%
      eosinophils). Despite supportive treatment the puppy's condition deteriorated
      rapidly; euthanasia was requested, and a necropsy performed. Microscopically,
      there was marked necrosuppurative and eosinophilic hepatitis with vasculitis.
      Numerous hepatocytes contained protozoal organisms suspected to be Toxoplasma
      gondii or Neospora caninum. However, serum was negative for both T gondii and N
      caninum antibodies; polymerase chain reaction assay on hepatic tissue was
      negative for both organisms; and immunohistochemical evaluation of hepatic tissue
      using serum raised against T gondii, N caninum, and Sarcocystis neurona also was
      negative. Schizont morphology suggested that merozoites replicated by
      endopolygeny, forming rosettes around a central residual body. Transmission
      electron microscopy revealed that merozoites lacked rhoptries. These findings
      were consistent with a diagnosis of Sarcocystis canis, an apicomplexan parasite
      with an unknown life cycle.

PMID- 16967427
TI  - Cutaneous metastasis of primary appendicular osteosarcoma in a dog.
AB  - A 6-year-old, neutered male Rottweiler was presented to the University of
      Illinois Veterinary Teaching Hospital because of a lytic bone lesion involving
      the distal portion of the right radius and possible pulmonary metastases on
      thoracic radiographs. Results of serum biochemical analysis were unremarkable.
      Aspiration and cytologic examination of the bone lesion indicated likely sarcoma
      with reactive bone. Cutaneous masses were found on the left thigh, interscapular
      region, and dorsal lumbar region, 4 weeks after initial presentation. Neoplastic
      spindle cells were found in aspirates from 2 of the masses. The neoplastic cells
      stained positive for alkaline phosphatase activity using cytochemistry. Re
      evaluation of serum biochemical values at this time revealed a marked increase in
      alkaline phosphatase activity (413 U/L, reference interval 12-110 U/L) compared
      with the initial value (26 U/L). Due to progressive disease, the dog was
      euthanized and a necropsy was performed. Histologic findings included primary
      osteosarcoma of the distal portion of the right radius, with metastases in the
      lungs, spleen, left fourth and fifth ribs, soft tissue of the right medial thigh,
      and T1-T3/interscapular region. Cutaneous metastasis of primary appendicular
      osteosarcoma has been reported rarely in animals and humans. Increased serum
      alkaline phosphatase activity may be a potential indicator of poor prognosis for
      this neoplasm.

PMID- 16967428
TI  - Hypernatremia associated with intracranial B-cell lymphoma in a cat.
AB  - An 8-year-old, spayed female, domestic shorthair cat with a history of
      hyperthyroidism, anorexia, dehydration, cervical ventroflexion, and behavioral
      changes was referred to the Iowa State University College of Veterinary Medicine.
      The cat was obtunded, with severe dehydration (15%) and hypothermia (86 degrees
      F), and severe muscle atrophy and fasciculations. Serum biochemical abnormalities
      included severe hypernatremia (195 mmol/L, reference interval 155-165 mmol/L),
      hyperchloridemia (161 mmol/L, reference interval 123-131 mmol/L), and hypokalemia
      (3.6 mmol/L, reference interval 4.0-5.7 mmol/L). Calculated osmolality was 418
      mOsm/kg (reference interval 280-305 mOsm/kg), attributable to the hypernatremia.
      The cat was kept warm and given fluid and glucocorticoid therapy and supportive
      measures but remained unresponsive. Hypernatremia and hyperosmolality improved
      through day 3, when the cat died suddenly. At necropsy, a 1.25-cm mass was found
      in the area of the thalamus and interthalamic adhesion that extended to the
      ventral aspect of the cerebrum. The histologic and immunohistochemical diagnosis
      was B-cell lymphoma. Hypernatremia and hyperosmolality in this cat were
      attributed to primary adipsia and hypothalamic dysfunction secondary to
      effacement of central nervous system tissue by neoplastic lymphocytes. To the
      authors' knowledge, this is the first reported case of central nervous system
      lymphoma, confirmed by use of immunohistochemical analysis as a B-cell phenotype,
      associated with hypernatremia. It also is the first reported case of lymphoma in
      animals limited to the thalamus, hypothalamus, and cerebrum, with no involvement
      of the spinal cord.

PMID- 16967431
TI  - D and 18O enrichment measurements in biological fluids in a continuous-flow
      elemental analyser with an isotope-ratio mass spectrometer using two
      configurations.
AB  - In doubly labelled water studies, biological sample enrichments are mainly
      measured using off-line techniques (equilibration followed by dual-inlet
      introduction) or high-temperature elemental analysis (HT-EA), coupled with an
      isotope-ratio mass spectrometer (IRMS). Here another continuous-flow method, (CF
      EA/IRMS), initially dedicated to water, is tested for plasma and urine analyses.
      The elemental analyser configuration is adapted for each stable isotope: chromium
      tube for deuterium reduction and glassy carbon reactor for 18O pyrolysis. Before
      on-line conversion of water into gas, each matrix is submitted to a short and
      easy treatment, which is the same for the analysis of the two isotopes. Plasma is
      passed through centrifugal filters. Urine is cleaned with black carbon and
      filtered (0.45 microm diameter). Tested between 150 and 300 ppm in these fluids,
      the D/H ratio response is linear with good repeatability (SD<0.2 ppm) and
      reproducibility (SD<0.5 ppm). For 18O/16O ratios (from 2000 to 2200 ppm), the
      same repeatability is obtained with a between-day precision lower than 1.4 ppm.
      The accuracy on biological samples is validated by comparison to classical dual
      inlet methods: 18O analyses give more accurate results. The data show that
      enriched physiological fluids can be successfully analysed in CF-EA/IRMS.

PMID- 16967433
TI  - Is lGnRH-III the most potent GnRH analog containing only natural amino acids that
      specifically inhibits the growth of human breast cancer cells?
AB  - Analogs of the decapeptide, gonadotropin-releasing hormone (GnRH), used in the
      treatment of hormone-dependent tumors, contain numerous unnatural amino acids,
      giving rise to many adverse effects. lGnRH-III, a natural isoform of GnRH
      isolated from the sea lamprey, is a weak agonist of GnRH in the pituitary, but
      inhibits the growth of human cancer cells in micromolar concentrations. As lGnRH
      III is not a natural ligand in humans, it is possible that a more potent peptide,
      also containing only natural amino acids, can be synthesized. A positional
      scanning peptide library, focused on the variable region of the GnRH family of
      peptides, residues 5-8, was synthesized. The synthesized peptides were analyzed
      in competitive binding experiments and six new analogs were designed on the basis
      of the results. Their biological activities were evaluated in cell growth
      experiments. The only natural sequence selected was chicken GnRH-II. The
      synthetic library did not yield a more potent peptide than lGnRH-III.

PMID- 16967434
TI  - Purification and characterization of the central segment of prothymosin-alpha:
      methodology for handling highly acidic peptides.
AB  - Prothymosin-alpha is a highly acidic protein consisting of 110 amino acids. The
      central segment of this protein, residues 51-89, is thought to be involved in
      metal binding which may be necessary for its physiological function. To carry out
      studies of this peptide, this central segment was synthesized in a linear fashion
      using Fmoc-based methods on rink amide MBHA resin. However, this peptide could
      not be purified with the typical straightforward approach of RP HPLC followed by
      negative mode electrospray ionization mass spectrometry (ESI-MS). This was
      attributed to the high proportion of acidic residues: 26 out of the 39 residues
      are aspartic and glutamic acids. The acidity of the peptide prevented retention
      on the RP HPLC column. Additionally, the ability of the highly negatively charged
      peptide to retain sodium ions prevented molecular weight determination with ESI
      MS. A systematic approach to the purification of this highly acidic peptide was
      undertaken. Ultimately, strong anion exchange chromatography was used to purify
      the peptide. Extensive desalting using dialysis was required prior to ESI-MS, and
      the choice of the buffer proved to be critical. In the end, a purification method
      was devised that yielded a highly purified peptide and is readily compatible with
      analysis by ESI-MS.

PMID- 16967435
TI  - Synthesis and biological activity of homoarginine-containing opioid peptides.
AB  - Two tris-alkoxycarbonyl homoarginine derivatives, Boc-Har{omega,omega'-[Z(2Br)]2}
      OH and Boc-Har{omega,omega'-[Z(2Cl)]2}-OH, were prepared by guanidinylation of
      Boc-Lys-OH, and used for the synthesis of neo-endorphins and dynorphins. The
      results were compared with that obtained in the synthesis in which Boc-Lys(Fmoc)
      OH was incorporated into the peptide chain, and after removing Fmoc protection,
      the resulting peptide-resin was guanidinylated with N,N'-[Z(2Br)]2- or N,N'
      [Z(2Cl)]2-S-methylisourea. The peptides were tested in the guinea-pig ileum (GPI)
      and mouse vas deferens (MVD) assays. The results indicated that replacement of
      Arg by Har may be a good avenue for the design of biologically active peptides
      with increased resistance to degradation by trypsin-like enzymes.

PMID- 16967436
TI  - High operative risk of cool-tip radiofrequency ablation for unresectable
      pancreatic head cancer.
AB  - BACKGROUND AND OBJECTIVES: To report and discuss the effect, complications and
      mortality of cool-tip radiofrequency ablation (RFA) for unresectable pancreatic
      cancer. METHODS: During October 2003 to July 2004, sixteen patients with
      unresectable pancreatic cancer were treated by open cool-tip RFA. One-half of the
      16 patients had tumors located in the pancreatic head. A 5-mm minimum safe
      distance between RFA site and major peripancreatic vessels was kept to avoid
      injury to the vessels. RESULTS: Six of twelve patients with back pain got pain
      relief postoperatively. Pancreatic fistula occurred in three patients (18.8%) and
      healed smoothly in 7-10 days with routine abdominal drainage. The mortality was
      25% (4/16). In the four death cases, tumors were all located in the pancreatic
      head; three patients with tumor close to portal vein died suddenly of massive
      gastrointestinal hemorrhage on the 4th, 30th, 40th postoperative day respectively
      and a 79-year-old patient died of acute renal failure on the 2nd postoperative
      day. CONCLUSIONS: Standard use of cool-tip RFA was dangerous for pancreatic head
      cancer close to portal vein, in which a 5-mm minimum safe distance between RFA
      site and major peripancreatic vessels might not be enough to avoid injury to the
      vessels.

PMID- 16967437
TI  - Management of goblet cell carcinoid.
AB  - BACKGROUND AND OBJECTIVES: Goblet cell carcinoid, a rare tumor of intermediate
      malignant potential, is known to account for a significant minority of
      appendiceal neoplasms. Sixteen new cases of gastrointestinal goblet cell
      carcinoid were reviewed to describe their presentation, treatment, and outcome.
      METHODS: A review of 16 cases from a single institution. RESULTS: Sixteen
      patients were diagnosed with goblet cell carcinoid between 1995 and 2005.
      Presenting diagnoses included appendicitis (n=8), abdominal or liver mass (n=5),
      uterine fibroids (n=1), ovarian mass (n=1), and Crohn's Disease exacerbation
      (n=1). Mean follow-up was 12 months with a mortality of 19% (n=3). Patients were
      divided into two groups: those where the diagnosis was an incidental finding at
      operation (Group 1) and those where the presentation was of an abdominal mass or
      metastatic disease (Group 2). Nine of ten patients in Group 1 initially received
      appendectomies. Group 2 included patients presenting with Krukenberg type lesions
      (n=2) and abdominal masses (n=4). CONCLUSIONS: Goblet cell carcinoid is a rare
      malignant tumor largely affecting the appendix. In patients presenting with
      appendicitis, our series does not support the recommendation of right
      hemicolectomy based on pathologic diagnosis alone and surgical intervention must
      be customized to the individual patient.

PMID- 16967438
TI  - Cyclic insulin-regulated aminopeptidase (IRAP)/AT4 receptor ligands.
AB  - The angiotensin IV receptor (AT4 receptor) is the insulin-regulated
      aminopeptidase enzyme (IRAP, EC 3.4.11.3). This membrane-spanning enzyme belongs
      to the M1 family of zinc-dependent metallo-peptidases. It has been proposed that
      AT4 receptor ligands exert their physiological effects by binding to the active
      site of IRAP and thereby inhibiting the catalytic activity of the enzyme. The
      biological activity of a large series of linear angiotensin IV analogs was
      previously disclosed. Herein, the synthesis and biological evaluation of a series
      of angiotensin IV analogs, encompassing macrocyclic ring systems of different
      sizes, are presented. It is demonstrated that disulfide cyclizations of
      angiotensin IV can deliver ligands with high IRAP/AT4 receptor affinity. One
      ligand, with an 11-membered ring system (4), inhibited human IRAP and
      aminopeptidase N (AP-N) activity with similar potency as angiotensin IV but was
      considerably more stable than angiotensin IV toward enzymatic degradation. The
      compound provides a promising starting point for further optimization toward more
      drug-like derivatives. The cyclic constrained analogs allowed us to propose a
      tentative bioactive conformation of angiotensin IV and it seems that the peptide
      adopts an inverse gamma-turn at the C-terminal.

PMID- 16967439
TI  - Detecting and characterizing reactive metabolites by liquid chromatography/tandem
      mass spectrometry.
AB  - Metabolic activation of a drug leading to reactive metabolite(s) that can
      covalently modify proteins is considered an initial step that may lead to drug
      induced organ toxicities. Characterization of reactive metabolites is critical to
      designing new drug candidates with an improved toxicological profile. High
      performance liquid chromatography (HPLC) coupled with mass spectrometry (MS)
      predominates over all analytical tools used for screening and characterization of
      reactive metabolites. In this review, a brief description of experimental
      approaches employed for assessing reactive metabolites is followed by a
      discussion on the reactivity of acyl glucuronides and acyl coenzyme A thioesters.
      Techniques for high-throughput screening and quantitation of reactive metabolite
      formation are also described, along with proteomic approaches used to identify
      protein targets and modification sites by reactive metabolites. Strategies for
      dealing with reactive metabolites are reviewed. In conclusion, we discuss the
      challenges and future needs in this field of research.

PMID- 16967440
TI  - Sustained release pellets based on poly(N-isopropyl acrylamide): matrix and in
      situ photopolymerization-coated systems.
AB  - The usefulness of poly(N-isopropyl acrylamide), PNIPA, for preparing sustained
      release matrix or photopolymerization-coated cellulosic pellets was evaluated.
      Theophylline pellets and granules were prepared using powdered cellulose (PC),
      poly(vinylpyrrolidone) (PVP), and PNIPA of Mw approximately 330 kDa, Mn
      approximately 93 kDa and low critical solubility temperature approximately 32
      degrees C. The low consistency of wet mass, evaluated by torsion rheometry, due
      to hydrophilic character of PNIPA at room temperature, favored extrusion
      spheronization. Theophylline (20%) pellets prepared with 15% PNIPA, 20% PVP and
      45% PC, and granules obtained using 40% PNIPA and 40% PC showed an enhanced,
      although limited, ability to sustain the release. This effect was notably
      promoted after compression (which provides slowly eroding tablets) or coating of
      individualized pellets. A new coating technique consisting in forming the polymer
      film by photo-polymerization/cross-linking of NIPA monomers on pellets surface,
      using a photoinitiator and UV-irradiation at 366 nm, was developed. The
      composition of coating mixture and the time of irradiation were optimized using
      oscillatory rheometry. Coating did not significantly change the shape, size, or
      friability of the pellets but remarkably decreased the porosity and sustained
      drug release for several hours. In situ formation and cross-linking of PNIPA on
      the pellet appears as a feasible way for controlling drug release.

PMID- 16967441
TI  - Health profiles of younger and older breast cancer survivors.
AB  - BACKGROUND: Over the past several decades, the incidence of prolonged survival
      after a diagnosis of cancer has increased; however, little is known regarding the
      long-term health profiles of cancer survivors in general and of breast cancer
      survivors in particular. To obtain more information concerning the consequences
      of surviving breast cancer, the authors conducted a large-scale health survey of
      patients who had been treated for the disease at their institution. METHODS: A
      descriptive analysis of information was provided by cancer survivors. Of the
      breast cancer survivors who were studied, 695 women were age < 45 years, 580
      women were between ages 46 years and 54 years, and 655 women were age > 55 years
      at the time of diagnosis. Their medical and psychosocial responses were analyzed
      and compared with those of age-matched responders in a national survey. RESULTS:
      Younger breast cancer survivors received chemotherapy more often than older
      survivors and were more likely to report memory loss and that cancer had affected
      their overall health adversely. Several other differences in physiologic and
      psychosocial characteristics, such as interpersonal relationships, also emerged.
      CONCLUSIONS: Physiologic and psychosocial differences distinguished younger
      breast cancer survivors from older breast cancer survivors. The findings of this
      study suggested that a systematic analysis of cancer survivors is needed to
      understand their unique health profiles and needs.

PMID- 16967442
TI  - Clinical outcome of anaplastic thyroid carcinoma treated with radiotherapy of
      once- and twice-daily fractionation regimens.
AB  - BACKGROUND: The purpose was to assess local control, survival, and toxicity after
      radiotherapy in patients with anaplastic thyroid carcinoma, and to compare
      clinical outcomes between once-daily and twice-daily fractionation regimens.
      METHODS: A retrospective review of patients with anaplastic thyroid carcinoma (n
      = 47) who underwent external beam radiotherapy from 1983 to 2004 was conducted.
      Twenty-three patients underwent radical radiotherapy with a radiation dose > 40
      Gy, and 24 patients underwent palliative radiotherapy with a dose < or = 40 Gy.
      Of radical radiotherapy, radiation was given with once-daily (14 patients) or
      twice-daily fractionation (9 patients; 1.5 Gy per fraction) to a total dose of 45
      66 Gy. Most patients (37 patients; 78.7%) were followed to death. RESULTS: The 6
      month local progression-free rate in patients who underwent radical radiotherapy
      was 94.1%, significantly higher compared with palliative radiotherapy (64.6%; P =
      .02). The median actuarial overall survival was greater in patients with radical
      radiotherapy (11.1 months) compared with palliative radiotherapy (3.2 months; P <
      .0001). The median overall survival in patients with twice-daily fractionation
      (13.6 months) was 3.3 months longer than patients treated with once-daily
      fractionation (10.3 months), but the difference was not statistically significant
      (P = .3). For patients treated with twice-daily fractionation, 3 patients had
      Grade 3 acute skin toxicity, and no patient had Grade 3 or higher esophageal
      toxicity. CONCLUSIONS: Radiotherapy can result in local control of anaplastic
      thyroid carcinoma. A twice-daily fractionation regimen is well tolerated and has
      a trend to longer survival, which deserves a larger study.

PMID- 16967443
TI  - Recreational physical activity and survival among young women with breast cancer.
AB  - BACKGROUND: Most epidemiologic studies report a reduced risk of developing breast
      cancer associated with higher levels of recreational physical activity, but
      little is known regarding its effect on prognosis. METHODS: In this study, the
      authors investigated whether activity undertaken prior to diagnosis influenced
      breast cancer survival in a population-based cohort. A follow-up study was
      conducted among 1264 women ages 20 to 54 years who were diagnosed with invasive
      breast cancer between 1990 and 1992. Women in the study were interviewed within
      several months of diagnosis and were asked about their average frequency of
      moderate and vigorous activity at age 13 years, age 20 years, and during the year
      before diagnosis. With 8 to 10 years of follow-up, all-cause mortality status was
      determined by using the National Death Index (n = 290 deaths). RESULTS: A modest
      reduction in the hazards ratio (HR) was observed for the highest quartile of
      activity in the year before diagnosis compared with the lowest quartile (stage
      adjusted and income-adjusted HR, 0.78; 95% confidence interval [95% CI], 0.56
      1.08). High activity was associated with a reduced HR among women who were
      overweight or obese at the time of diagnosis (HR, 0.70; 95% CI, 0.49-0.99) but
      not among ideal weight or underweight women (HR, 1.08; 95% CI, 0.77-1.52). A
      reduced HR was not evident for activity at age 13 years or 20 years or for
      average activity across the 3 periods studied. CONCLUSIONS: The results of this
      study provided some suggestive evidence for a beneficial effect on survival of
      recreational physical activity undertaken in the year before diagnosis,
      particularly among women who are overweight or obese near the time of diagnosis.

PMID- 16967444
TI  - Treatment of acute myelogenous leukemia with outpatient azacitidine.
AB  - BACKGROUND: Patients older than 55 years of age with acute myelogenous leukemia
      (AML) are less likely to achieve complete remission and more likely to experience
      toxicity with conventional induction chemotherapy than younger patients.
      Azacitidine administered in the outpatient setting is well tolerated and can
      induce complete hematological remission in patients with myelodysplastic
      syndromes (MDS). At higher doses, azacitidine has activity in AML. METHODS:
      Twenty patients were retrospectively identified who had been treated with
      azacitidine with bone marrow blast counts between 21 and 38%. Patients with blast
      counts up to 29% were initially treated as MDS, but by WHO now meet criteria for
      AML. Patients with blast counts over 29% were treated with azacitidine after
      being deemed poor candidates for induction chemotherapy. Azacitidine 75 mg/m2/day
      was administered subcutaneously for 7 days every 4 weeks, which was defined as 1
      cycle. RESULTS: The overall response rate was 60% (12/20): complete response (CR;
      n = 4; 20%); partial response (PR; n = 5; 25%); hematologic improvement (HI; n =
      3; 15%). The median survival of responders was 15+ months compared with 2.5
      months for nonresponders (P = .009). During therapy, responders had an Eastern
      Cooperative Oncology Group (ECOG) performance status of 1 or 0. The most common
      toxic event was infection (n = 8). Four patients were hospitalized during the
      first cycle of treatment. CONCLUSIONS: Azacitidine administered in the outpatient
      setting can induce remission in AML. The therapy is well tolerated and might be
      an alternative for patients unlikely to tolerate standard induction chemotherapy.

PMID- 16967445
TI  - Neoadjuvant intratumoral cytokine-loaded microspheres are superior to
      postoperative autologous cellular vaccines in generating systemic anti-tumor
      immunity.
AB  - BACKGROUND: Sustained intratumoral cytokine release using poly-lactic acid
      microspheres (PLAMs) can induce a systemic immune response, shifting
      immunotherapy to the neoadjuvant setting. METHODS: C57BL6 mice with established
      B16 melanomas underwent a single intralesional injection of IL-12, TNF-alpha or
      GM-CSF PLAM, alone or in combination. Tumor draining lymph nodes (TDLN) and
      spleens were assessed for a specific anti-tumor response by IFNgamma release
      assay and ELISPOT. RESULTS: Intralesional injection of TNF-alpha, alone or in
      combination, resulted in significant tumor ablation. The induction of tumor
      specific reactive T-cells in the TDLN was greatest with IL-12 and TNF-alpha. Only
      mice treated with IL-12 and TNF-alpha demonstrated a substantial T-cell response
      in cultured splenocytes. This combination resulted in a significant reduction in
      new tumors after re-challenge. Adjuvant therapy, using irradiated B16 cells in
      combination with equivalent doses of IL-12 and TNF-alpha, failed to generate a
      similar T-cell response or prevent re-challenge. CONCLUSIONS: Intratumoral IL-12
      and TNF-alpha loaded PLAM leads to both local eradication of tumor and the
      induction of specific anti-tumor T-cells in the lymph nodes and spleens,
      resulting in memory immune response. Neoadjuvant treatment was significantly
      superior to postoperative autologous cellular vaccines using IL-12 and TNF-alpha
      PLAM.

PMID- 16967446
TI  - Application of capillary electrophoresis mass spectrometry to the
      characterization of bacterial lipopolysaccharides.
AB  - Capillary electrophoresis (CE) is a high-resolution technique for the separation
      of complex biological mixtures and has been widely applied to biological
      analyses. The coupling of capillary electrophoresis with mass spectrometry (MS)
      provides a powerful approach for rapid identification of target analytes present
      at trace levels in biological matrices, and for structural characterization of
      complex biomolecules. Here we review the analytical potential of combined
      capillary electrophoresis electrospray mass spectrometry (CE-MS) for the analysis
      of bacterial lipopolysaccharides (LPS). This hyphened methodology facilitates the
      determination of closely related LPS glycoform and isoform families by exploiting
      differences in their unique molecular conformations and ionic charge
      distributions by electrophoretic separation. On-line CE-MS also provides an
      additional avenue to improve detection limits, which has been successfully
      applied to directly probe oligosaccharide LPS glycoform populations of bacteria
      isolated from infected animal models without the need for further passage.

PMID- 16967447
TI  - High expressions of CD105 and VEGF in early oral cancer predict potential
      cervical metastasis.
AB  - BACKGROUND AND OBJECTIVES: Although elective neck dissection has become a popular
      treatment modality for early oral cancer among most head and neck surgeons, a
      large portion of patients revealed pathological N0 postoperatively. Our study is
      aimed to evaluate the expressions of the angiogenic factors, vascular endothelial
      growth factor (VEGF), and CD105 (endoglin) on the prediction of neck metastasis
      for clinical N0 patients in early oral cancer. PATIENTS AND METHODS: Between July
      1996 and July 2005, the preoperative biopsy specimens among 176 patients who
      underwent surgical treatment for early oral cancer were retrieved for the
      immunohistochemical study for VEGF and CD105. RESULTS: High expressions of CD105
      and VEGF significantly correlated with positive nodal metastasis, respectively
      (P<0.001). The expression of CD105 also significantly correlated with that of
      VEGF (P<0.001). Furthermore, the sensitivity and specificity for prediction of
      cervical metastasis by high expressions of CD105 versus VEGF were 81.8% and 97.7%
      versus 93.2% and 72%, respectively. Low expression of CD105 and VEGF also
      significantly correlated with higher survival rate, respectively (P<0.001).
      CONCLUSIONS: Besides the image studies, the expressions of both CD105 and VEGF
      could be useful to guide the elective treatment for clinical N0 neck in early
      oral cancer.

PMID- 16967448
TI  - The effect of valence on the ion-exchange process: theoretical and experimental
      aspects on compound binding/release.
AB  - The effect of valence of mobile counter-ions (extracting electrolytes), mobile co
      ions, and drug-like compounds was evaluated on drug binding/release in ion
      exchange fibers. The experimental results support the Donnan theory and suggest
      that incorporation of monovalent salicylic acid (SA) and divalent 5
      hydroxyisophthalic acid (di-COOH) into the anion-exchange fibers was attained
      mainly as a result of electrostatic (ionic) interaction, with additional
      contribution of non-electrostatic interactions. Increasing the capacity of ion
      exchanger increased the molar amount of compound loading. More efficient release
      of model anions was observed at increasing valence or concentration of the
      extracting counter-ion. Potency to release the compounds decreased in the order
      of citrate (-3) > sulfate (-2) > chloride (-1). The valence of co-ions (sodium
      (+1) vs. calcium (+2)) in the external solution had only a slight effect on the
      release. Due to dual site binding (two ionized carboxylate groups), the amount of
      di-COOH bound into the fibers was half of that of monovalent SA. Also the release
      was significantly reduced, as the electrostatic interaction was stronger in the
      case of divalent compound. Simulations on the effect of valence on the Donnan
      potential and theoretical modeling of the release efficiencies by the external
      ions supported successfully the conclusions above.

PMID- 16967450
TI  - Matrix-free methods for laser desorption/ionization mass spectrometry.
AB  - Matrix assisted laser desorption/ionization (MALDI) is a soft ionization mass
      spectrometric method that has become a preeminent technique in the analysis of a
      wide variety of compounds including polymers and proteins. The main drawback of
      MALDI is that it is difficult to analyze low molecular weight compounds (<1,000
      m/z) because the matrix that allows MALDI to work interferes in this mass range.
      In recent years there has been considerable interest in developing laser
      desorption/ionization (LDI) techniques for the analysis of small molecules. This
      review examines the approaches to matrix-free LDI mass spectrometry including
      desorption/ionization on silicon (DIOS), sol-gels, and carbon-based
      microstructures. For the purposes of this review matrix-free methods are defined
      as those that do not require matrix to be mixed with the analyte and therefore
      does not require co-crystallization. The review will also examine mechanisms of
      ionization and applications of matrix-free LDI-MS.

PMID- 16967451
TI  - Colchicine delays the development of hepatocellular carcinoma in patients with
      hepatitis virus-related liver cirrhosis.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant neoplasm associated
      with liver cirrhosis, with an annual incidence of 3% to 9%, which is one of the
      main causes of death in patients with cirrhosis. Viral hepatitis is associated
      with an increased risk of HCC, probably due to an inflammatory reaction.
      Colchicine is an antiinflammatory agent that inhibits the formation of
      intracellular microtubules, affecting mitosis and fibrogenesis. Diverse clinical
      studies have failed to demonstrate the benefit of colchicine over the progression
      of fibrosis in patients with liver cirrhosis; nevertheless, to the authors'
      knowledge there are no studies that evaluate its effect in the development of
      HCC. METHODS: The effect of the administration of colchicine on the development
      of HCC was evaluated in 186 patients with hepatitis virus-related liver cirrhosis
      in a retrospective cohort study. The minimum follow-up time was 3 years (median,
      84 months +/- 2.8 months). One hundred sixteen patients received treatment with
      colchicine. The characteristics of both groups were similar. RESULTS: The
      percentage of patients who developed HCC was significantly smaller in the
      colchicine group when compared with the noncolchicine group (9% vs. 29%; P =
      .001). On multivariate analysis, an alpha-fetoprotein level > or = 5 ng/dL (P =
      .03), a platelet count < 100,000 at diagnosis (P = .05), alanine aminotransferase
      > or = 52 IU (P = .006), and a lack of treatment with colchicine (P = .0001) were
      found to be associated with an earlier development of HCC. The average time for
      the development of HCC was 222 months +/- 15 months and 150 months +/- 12 months
      in the patients who received and who did not receive colchicine, respectively.
      CONCLUSIONS: The results suggest that treatment with colchicine prevents and
      delays the development of HCC in patients with hepatitis virus-related cirrhosis.
      The protective mechanisms of colchicine over the development of HCC could be
      related to antiinflammatory properties and inhibition of mitosis. Prospective
      studies to confirm this observation with a greater number of patients and long
      term follow-up may be indicated.

PMID- 16967452
TI  - Clinical factors affecting acquired resistance to gefitinib in previously treated
      Japanese patients with advanced nonsmall cell lung cancer.
AB  - BACKGROUND: The risk factors for the development of acquired resistance in
      nonsmall cell lung cancer (NSCLC) patients responding to gefitinib are unclear.
      The current study assessed clinicopathologic factors affecting acquired
      resistance to gefitinib in previously treated patients with advanced NSCLC.
      METHODS: Between 2000 and 2004, 197 consecutive Japanese patients with advanced
      NSCLC underwent treatment with gefitinib. Of these patients, 56 who had continued
      gefitinib treatment without disease progression for at least 6 months were
      included in the study. RESULTS: At a median follow-up time of 21.6 months (range,
      7.7-59.7 months), the median time to disease progression was 19.5 months, with
      progression-free survival rates of 68.5% at 1 year, 33.6% at 2 years, and 21.2%
      at 3 years. In a multivariate analysis using a Cox regression model, baseline
      brain metastasis was the strongest prognostic factor affecting acquired
      resistance to gefitinib (hazards ratio, 2.14; 95% confidence interval, 1.10- 4.17
      [P = .025]). In addition, a decreased baseline hemoglobin level (P = .074) and
      the administration of >1 chemotherapy regimen before gefitinib treatment (P =
      .069) tended to be significant negative prognostic factors. CONCLUSIONS: In
      patients undergoing treatment with gefitinib, the presence of brain metastasis
      was strongly associated with the emergence of acquired resistance in the current
      series of NSCLC patients. The finding requires confirmation in a large cohort of
      patients with advanced NSCLC, including a non-Japanese/Asian population.

PMID- 16967453
TI  - Accumulation of beta-catenin protein, mutations in exon-3 of the beta-catenin
      gene and a loss of heterozygosity of 5q22 in solid pseudopapillary tumor of the
      pancreas.
AB  - BACKGROUND: Solid pseudopapillary tumors (SPT) of the pancreas are neoplasms with
      a low malignant potential. The molecular events contributing to the pathogenesis
      of SPTs are still unknown. OBJECTIVES: This study was intended to help better
      understand the early steps of human SPT development. METHODS: We microdissected
      20 SPTs and normal pancreatic tissue. In addition, we examined the DNA from each
      SPT for mutations in exon-3 of beta-catenin and loss of heterozygosity (LOH) on 9
      chromosome arms using 10 microsatellite markers. Immunohistochemical staining for
      beta-catenin was performed. RESULTS: Activating mutations between codons 32 and
      37 of beta-catenin exon-3 were present in 16 cases (80%). Allelic loss on
      chromosome 5q22.1 was present in 10 cases (55.5%), while no allelic loss was
      found on chromosomes 1p, 6q, 9p, 9q, 11p, 11q, 17p, or 22q. Nuclear accumulation
      of beta-catenin was found in 20 cases (100%). CONCLUSION: Mutations in exon-3 of
      the beta-catenin gene, nuclear accumulation of beta-catenin, and LOH on
      chromosome 5q22.1 in SPT tissue suggest that these mutations are involved in SPT
      tumorigenesis.

PMID- 16967455
TI  - Staging of esophageal carcinoma: length of tumor and number of involved regional
      lymph nodes. Are these independent prognostic factors?
AB  - BACKGROUND AND OBJECTIVES: New potential prognostic indicators aside from the TNM
      classification have been proposed. The aim of this study was to analyze the
      prognostic relevance of tumor length as well as number of involved regional lymph
      nodes (LNM) in patients with esophageal carcinoma. METHODS: Two hundred thirteen
      patients with esophageal carcinoma (116 squamous cell- and 97 adenocarcinoma)
      were included in this study. Treatment of choice was subtotal en bloc
      esophagectomy including "2-field" lymphadenectomy. The median number of examined
      lymph nodes (LNs) was 28. Eighty patients (38%) received preoperative radio
      chemotherapy according to a standardized protocol. Histopathology consisted of
      tumor stage, residual tumor, grading, and number of examined and involved LN.
      Univariate and multivariate prognostic values were calculated. RESULTS: Length of
      tumor correlated with pT/ypT-category (P<0.01). Univariate but not multivariate
      analysis showed better survival for tumors<or=3 cm (P<0.05). Patients with 1-5
      LNM had significantly better prognoses than those with more than 5 LNM (Hazard
      ratio 2.7, 95% CI=1.7-4.2) (P<0.01). Patients without LNM and more than 15
      examined LN showed significantly better prognosis than those with fewer examined
      LN (Hazard ratio=0.3, 95% CI=0.1-0.6) (P<0.01). CONCLUSIONS: A revision of the
      TNM classification for esophageal carcinoma should subdivide the pN1-category
      according to the number of LNM.

PMID- 16967456
TI  - Added value of ultrasound in screening the clinically negative axilla in breast
      cancer.
AB  - BACKGROUND: For staging purposes in breast cancer it is current practice to
      perform a sentinel node biopsy in a clinically negative axilla, followed by an
      axillary lymph node dissection if metastases are found in the sentinel node. To
      limit the number of surgical procedures it is therefore of importance to try and
      identify as much patients as possible who have axillary metastases. Clinical
      staging of the axillary nodes in breast cancer is mainly based on palpation, but
      ultrasound has been shown to be of additional value in detecting pathological
      nodes. METHODS: In this paper, we report our results of screening 131 breast
      cancer patients without palpable axillary nodes through ultrasound. RESULTS: Out
      of the 53 patients with axillary node involvement, 18 were identified as such by
      our radiologist, resulting in a detection score of 34%. DISCUSSION: This high
      rate is probably reached because of the limited number of radiologists performing
      this procedure, thereby rapidly increasing their experience.

PMID- 16967457
TI  - Ductal carcinoma in situ: value of sentinel lymph node biopsy.
AB  - BACKGROUND: Ductal carcinoma in situ (DCIS) represents about 20% of newly
      diagnosed breast carcinomas. Axillary metastasis is often related to undiagnosed
      DCIS with microinvasion (DCISM). The aim of this study was to confirm the
      interest of sentinel lymph node (SLN) biopsy in extensive DCIS. METHODS: Patients
      with a diagnosis of DCIS or DCISM and axillary lymph node evaluation were
      selected. Surgical treatment included SLN biopsy and/or axillary lymph node
      dissection (ALND). Serial sections were stained with hematoxylin and eosin (H&E)
      and with an immunohistochemical (IHC) method. When a micrometastasis was found,
      the breast specimen was revised searching for occult microinvasion. RESULTS:
      Hundred and forty patients with initial DCIS were enrolled in the study. Node
      metastasis was identified in 9 patients (7%) of the 128 patients with DCIS and
      DCISM. At final histology, 4 (10%) of the 39 patients with pure DCIS and SLN
      biopsy and 1 (7%) of the 14 patients with DCISM and SLN biopsy had axillary
      micrometastasis. Four of the 12 patients upstaged to invasive carcinoma had
      metastatic SLNs. CONCLUSIONS: Sentinel lymph node biopsy is valuable in patients
      with diffuse DCIS or DCISM who are scheduled for mastectomy in order to search
      for axillary micrometastases and occult breast microinvasion.

PMID- 16967458
TI  - Malignancies in organ transplant recipients.

PMID- 16967459
TI  - Extended right hemihepatectomy with extracorporeal circulation for liver
      mestastases invading the inferior vena cava and right atrium.

PMID- 16967460
TI  - Validation of a tool for identifying women at high risk for hereditary breast
      cancer in population-based screening.
AB  - BACKGROUND: Recent scientific advances provide the opportunity to identify women
      in the general population at increased breast cancer risk and to offer effective
      early detection and disease prevention interventions. METHODS: A pedigree
      assessment tool (PAT) was designed to identify women in primary care settings who
      are at increased risk for hereditary breast cancer, including potential BRCA
      mutation carriers. The PAT is a simple point-scoring system based on family
      cancer history with points weighted to account for features associated with a
      higher probability that a BRCA mutation is present. The ability of the PAT and
      the Gail model to accurately identify potential BRCA mutation carriers in 3,906
      women without a personal history of breast cancer presenting for a screening
      mammogram at a community hospital was tested. RESULTS: Eighty-six (2.2%) women
      had a family history indicative of a high probability (>10%) that a BRCA mutation
      was present within the family. The PAT performed better than the Gail model in
      correctly assigning women to the "high BRCA probability" cohort. The area under
      the receiver operating characteristic (ROC) curve for the PAT was 0.9625 compared
      with 0.389 and 0.5861 for the Gail model 5-year and lifetime risk estimates,
      respectively. At the optimal threshold score, the PAT performed with 100%
      sensitivity and 93% specificity. CONCLUSIONS: The PAT is a simple and accurate
      tool for identifying women at risk for the hereditary breast cancer syndromes
      that can be employed as part of a comprehensive breast cancer risk-screening
      strategy in the primary care setting.

PMID- 16967461
TI  - Primary angiosarcoma of the breast: observations in Asian Indian women.
AB  - BACKGROUND: Primary angiosarcomas of breast are rare tumors, with a fatal
      outcome. MATERIAL AND METHODS: We studied histological prognostic factors and c
      kit expression by immunohistochemistry (IHC) in 12 angiosarcomas accessioned at a
      cancer referral center in India. RESULTS: All patients had primary angiosarcoma;
      no case of secondary angiosarcoma was accessioned during the study period. Median
      age of patients was 24.5 years. Nine patients had intermediate grade tumors, one
      a well differentiated tumor and three patients had high-grade tumors. Interesting
      cases encountered included an epithelioid angiosarcoma and an angiosarcoma
      arising on the background of a biphasic tumor. Eight patients had lumpectomy,
      four mastectomy and two patients were given radiotherapy. Of the nine patients
      (seven type I/II and two high grade) with follow up, eight patients developed
      disseminated metastases within a year of presentation. The patient with well
      differentiated angiosarcoma also died of metastasis albeit after a longer time.
      On IHC c-kit staining was weakly seen in two cases. CONCLUSION: Primary
      angiosarcoma was fatal in young Indian women even in lower grade tumors. The low
      expression of c-kit on IHC suggests that targeting this protein for therapy may
      not be successful in treating these tumors.

PMID- 16967462
TI  - Ipsilateral breast tumor reappearance in patients treated with conservative
      surgery after primary chemotherapy. The role of surgical margins on outcome.
AB  - BACKGROUND AND OBJECTIVES: To evaluate the ipsilateral breast tumor reappearance
      (IBTR) rate after breast conservative surgery (BCS) following primary
      chemotherapy (PC) and to assess whether positive margins affects IBTR rate and
      overall survival (OS). METHODS: Three hundred nine women candidates for
      mastectomy received PC before surgery. One hundred ninety-five patients (63.1%)
      underwent BCS and 114 patients (36.9%) a modified radical mastectomy. RESULTS:
      After a median follow-up of 41 months (range 7-90), 13 patients of the 195
      treated with BCS had an IBTR (6.7%), 6 patients had a regional relapse (3.1%), 28
      women had distant metastases (14.4%). Twenty-three patients died of breast cancer
      (11.8%). Twenty-four patients treated with BCS had positive margins (12.3%). At 3
      years, the crude cumulative incidence of local recurrence was 4.7% in women with
      negative margins, and 13.3% in women with positive margins (P=0.05). Cumulative
      incidence of distant metastases was similar in patients with positive and
      negative margins (P=0.16) and there was no significant difference in terms of OS
      according to the margin status (P=0.577). CONCLUSIONS: BCS after PC has an
      acceptable rate of IBTR. After a short follow-up, the presence of positive
      margins does not affect OS.

PMID- 16967464
TI  - A simple method to identify supramolecules in action: Hill coefficients for
      exergonic self-assembly.
AB  - Precise supramolecular architecture is often essential for significant function.
      Simple methods to reliably and rapidly demonstrate the existence of such
      supramolecular structure and function at relevant concentrations in complex
      systems are badly needed. Hill plots, describing the dependence of a signal on
      the n-th power of the monomer concentration, are compatible only with the
      identification of supramolecules that do not really exist, that is, endergonic
      self-assembly (Litvinchuk et al., J Am Chem Soc 2004;126:10067). Here, we show
      that the artificial increase in monomer concentration by chemical denaturation
      restores compatibility of Hill plots with exergonic self-assembly and affords
      Hill coefficients n > 1 for stable supramolecules. Recent rigid-rod pi-stack
      architecture with photosynthetic and ion channel activity is used as timely
      example, circular dichroism (CD) spectroscopy as method of choice for both
      sensitive and selective detection under relevant conditions.

PMID- 16967466
TI  - Analysis of the 5HT-2A T102C receptor polymorphism and psychotic symptoms in
      Alzheimer's disease.
AB  - Although the aetiology of psychotic symptoms in Alzheimer's disease (AD) is multi
      factorial, alterations in serotonergic neurotransmission are often implicated.
      Polymorphisms of the serotonin receptor 5HT-2A are associated with hallucinatory
      symptoms and delusions in demented and non-demented cohorts. This study examined
      the role of the 5HT-2A T102C polymorphism in influencing psychotic symptoms in a
      large Northern Ireland AD population (n = 406, mean MMSE 13/30). Forty-eight
      percent of patients experienced delusional symptoms and 28% experienced
      hallucinations during the course of their dementia. No significant association
      was found either in frequency of genotype or allelic variation for either set of
      symptoms. Furthermore, the mean delusional and hallucinatory severity scores did
      not differ significantly among the three genotype groups. The lack of influence
      of the T102C polymorphism of the 5HT-2A receptor on the emergence of psychotic
      symptoms in AD contrasts with previous reports in other cohorts involving smaller
      numbers of subjects.

PMID- 16967465
TI  - Positive association of schizophrenia to JARID2 gene.
AB  - Dysbindin (DTNBP1) is a positional candidate gene for 6p22.3-linked schizophrenia
      (SZ). However, so far, no disease-causing alleles have been identified. DTNBP1 is
      immediately adjacent to JARID2, a member of the ARID (AT-rich interaction domain)
      family of transcription modulators. We have previously suggested that proteins
      which bind to AT-rich domains could play a role in SZ pathogenesis. Consequently,
      we explored the possibility that JARID2 itself could be a candidate gene for
      6p22.3-linked SZ. We used a case control design to analyze single nucleotide
      polymorphisms (SNPs) and insertion/deletion variants affecting AT-rich domains in
      both the DTNBP1 and JARID2 genes. Three of the DTNBP1 SNPs analyzed had
      previously been shown to be associated with SZ. We did not detect any significant
      difference in allele, genotype or haplotype distribution for any of these DTNBP1
      markers. However, we did detect a significant difference in allele distribution
      for a tetranucleotide repeat polymorphism in the JARID2 gene that affects an AT
      rich domain. A significant increase in short alleles (less than 11 repeats) was
      found in patients with SZ (chi(2) = 7.02; P = 0.008). No other JARID2 marker
      displayed statistically significant allele and genotype distributions. Our
      findings suggest that JARID2 should be viewed as a candidate gene for 6p22.3
      linked SZ.

PMID- 16967467
TI  - Tumour-positive sentinel node findings in patients with ductal carcinoma in situ.
AB  - BACKGROUND: Our aim was to evaluate the prevalence of and risk factors for tumour
      positive sentinel node (SN) findings in patients with ductal carcinoma in situ
      (DCIS). METHODS: Altogether 1,470 patients underwent sentinel node biopsy (SNB)
      between April 2001 and March 2005 in our unit. According to a histopathological
      review, 11 of them had microinvasive and 74 pure DCIS and were included in the
      study. RESULTS: Five patients (7%) with pure DCIS had SN metastases. Three of
      them had isolated tumour cells (ITC) only. Axillary clearance without further
      metastatic findings was performed in three patients. The median histological size
      of DCIS was larger, 50 (45-60) mm in patients with metastatic SN findings than
      the median of 18 (2-110) mm in those with tumour-negative SN, P=0.0103. All five
      patients with metastatic SN findings underwent mastectomy. Metastatic SN findings
      were detected in one (9%) patient with microinvasive DCIS. CONCLUSIONS:
      Metastatic SN findings in patients with pure DCIS may be a sign of missed
      invasion.

PMID- 16967468
TI  - Inflammatory myofibroblastic tumors.
AB  - INTRODUCTION: Inflammatory myofibroblastic tumors (IMT) while uncommon may arise
      within numerous organs. Historically, the literature regarding IMT has been
      confined to small one organ case series, with few reviews encompassing multiple
      anatomic sites, and little data regarding adjuvant treatment. METHODS: A review
      of patients with IMT treated at two large academic medical centers over a 15-year
      period was undertaken. Patient demographics, pathologic diagnoses, and pertinent
      clinical data were obtained. RESULTS: Forty-four cases of pathologically
      confirmed IMT were identified. Tumor locations included multiple anatomic sites.
      Therapies included complete resection, incomplete resection, observation, or
      chemotherapy, and/or radiation. Five patients underwent adjuvant chemotherapy
      and/or radiation therapy following surgery (14%) for local aggressiveness of the
      tumor, invasion, positive margins, or location of tumor that was not amenable to
      surgical resection. A second, concomitant, histologically distinct, neoplasm was
      identified in five cases. Of the patients who underwent treatment three local
      recurrences were noted (8%) and occurred in patients with partial resection
      without adjuvant chemo- or radiotherapy. CONCLUSIONS: Inflammatory
      myofibroblastic tumors may be a locally aggressive and destructive neoplasm.
      Tumor recurrence is unusual following complete surgical resection or organ
      preserving combined modality therapy.

PMID- 16967469
TI  - Association of tagSNPs in the urokinase-plasminogen activator (PLAU) gene with
      Alzheimer's disease and associated quantitative traits.
AB  - The gene coding for urokinase-plasminogen activator (PLAU) is a strong biological
      and positional candidate gene for Alzheimer's disease (AD). Previously some
      studies have examined the role of common variation in the PLAU gene with AD risk
      but the results have been inconsistent and this inconsistency could have been due
      to the use of relatively small sample sizes. In this study we evaluated the
      distribution of four tagSNPs (rs2227562 in intron 5, rs2227564 in exon 6,
      rs2227571 in intron 9, and rs4065 in 3'UTR) in the PLAU gene in a large case
      control study consisting of up to 1,000 AD patients and 697 white control
      subjects. We examined the role of these tagSNPs with AD risk and quantitative
      traits of AD, including age-at-onset (AAO), disease duration, and mini-mental
      state examination (MMSE) scores. The 3'UTR SNP revealed modest significant
      association with risk (OR = 0.71, 95% CI: 0.53-0.95; P = 0.02), AAO (P = 0.036)
      and disease duration (P = 0.04) of AD. In addition, the intron 9 SNP also
      revealed a significant association with AAO (P = 0.01) and disease duration (P =
      0.006). Our data on a large number of AD cases and controls suggest that genetic
      variation in PLAU may affect the risk and AAO of AD.

PMID- 16967470
TI  - Similar chromosomal changes in cisplatin and oxaliplatin-resistant sublines of
      the H69 SCLC cell line are not associated with platinum resistance.
AB  - Small cell lung cancer (SCLC) initially responds well to DNA damaging drugs such
      as cisplatin, however this is transitory as resistance normally develops. To
      investigate whether changes in chromosomal copy number caused by platinum drug
      treatment contributes to platinum resistance, we have analyzed H69 SCLC cells and
      two low-level platinum-resistant sublines, H69CIS200 and H69OX400, derived by
      cisplatin and oxaliplatin treatment, respectively. Affymetrix 10K SNP array
      showed that cisplatin and oxaliplatin have independently caused similar changes
      including loss of segments 6q21-qter and 13pter-13q.14.11 and duplication of
      chromosome 21. Interestingly, despite using equally cytotoxic doses of drug in
      the development of the cell lines, oxaliplatin caused three times more
      chromosomal changes than cisplatin. The resistant cell lines lose their resistant
      phenotype after 3 months of drug-free culture. The revertant cell lines, denoted
      H69CIS200-S and H69OX400-S, were also analyzed by Affymetrix array to determine
      if chromosomal changes associated with resistance remain after the resistant
      phenotype is lost. In the H69OX400-S many of the changes observed in the
      resistant cells were absent suggesting that they contributed to the resistant
      phenotype including: loss of 1q23.3-qter, 10q11.23, and 19q13.12-q13.2 and
      duplication of segments 6p21.2-p12.3, 16q12.1-16q13, 16q21-q23.1, and 19q12.
      However, out of the similar changes induced by cisplatin and oxaliplatin, both
      the loss of 6q21-qter and gain of 21 were still present in the H69CIS200-S and
      H69OX400-S cells. This suggests that cisplatin and oxaliplatin induced similar
      changes due to inherent vulnerabilities in the H69 cells rather than changes
      associated with platinum resistance.

PMID- 16967471
TI  - Anterior interosseous nerve conduction study: normative data.
AB  - Neurophysiological techniques assessing anterior interosseous nerve (AIN)
      function and employing surface electrode recordings from the flexor pollicis
      longus (FPL), have been limited by technical difficulties. The aim of this study
      was to describe a surface electrode recording technique of investigating the AIN
      by recording compound muscle action potentials (CMAPs) from FPL. CMAP responses
      exhibited a negative onset, suggesting that they originated from FPL, and this
      was confirmed by needle recording. Normative data has been established that may
      prove useful in future studies assessing pathological involvement of the anterior
      interosseous nerve.

PMID- 16967472
TI  - Double trouble (McArdle's disease and myasthenia gravis): how can exercise help?
AB  - We report a 29-year-old patient with McArdle's disease and myasthenia gravis. She
      had been debilitated with McArdle's disease since childhood (with marked
      rhabdomyolysis) and was obese. Myasthenia gravis was diagnosed at 24 years of
      age. After 3 months of aerobic exercise training, her exercise capacity increased
      significantly and she regained the ability to live independently. We conclude
      that even patients with profound neuromuscular diseases may benefit from
      carefully prescribed exercise training.

PMID- 16967473
TI  - Structural effects of crosslinking a biopolymer hydrogel derived from marine
      mussel adhesive protein.
AB  - In an effort to explore new biocompatible substrates for biomedical technologies,
      we present a structural study on a crosslinked gelatinous protein extracted from
      marine mussels. Prior studies have shown the importance of iron in protein
      crosslinking and mussel adhesive formation. Here, the structure and properties of
      an extracted material were examined both before and after crosslinking with iron.
      The structures of these protein hydrogels were studied by SEM, SANS, and SAXS.
      Viscoelasticity was tested by rheological means. The starting gel was found to
      have a heterogeneous porous structure on a micrometer scale and, surprisingly, a
      regular structure on the micron to nanometer scale. However disorder, or "no
      periodic structure", was deduced from scattering on nanometer length scales at
      very high q. Crosslinking with iron condensed the structure on a micrometer
      level. On nanometer length scales at high q, small angle neutron scattering
      showed no significant differences between the samples, possibly due to strong
      heterogeneity. X-ray scattering also confirmed the absence of any defined
      periodic structure. Partial crosslinking transformed the viscoelastic starting
      gel into one with more rigid and elastic properties.

PMID- 16967475
TI  - Quintessence from proteomics networks--the HUPO Brain Proteome Project Pilot
      Studies.

PMID- 16967476
TI  - Surface behavior and molecular recognition in DNA microarrays from N,N
      dimethylacrylamide terpolymers with activated esters as linking groups.
AB  - A series of terpolymers made of DMA, NAS and MAPS were synthesized by free
      radical copolymerization and used as functional coatings for the fabrication of
      glass slide DNA microarrays. The surface properties of coated glass slides were
      investigated through contact angle measurements, ellipsometry and atomic force
      microscopy. The terpolymer molecular weight showed a moderate effect on surface
      tension (gamma(s) = 56-62 mN x m(-1)), but no clear effect on polymeric layer
      thickness (5-8 nm) and roughness. Hybridization experiments with amine
      functionalized oligonucleotides gave the best fluorescence intensity results for
      microarrays coated with intermediate-molecular-weight terpolymers. Finally, an
      accelerated ageing test of the microarray in a humidity chamber showed a nice
      relationship between decay curves of contact angle against water and fluorescence
      intensity.

PMID- 16967477
TI  - Melt spinning of poly(3-hydroxybutyrate) fibers for tissue engineering using
      alpha-cyclodextrin/polymer inclusion complexes as the nucleation agent.
AB  - This paper reports on an attempt to use CD and CD/PHB ICs as nucleation agents
      for PHB in a high-speed melt spinning process. At first rheological and thermal
      properties of the nucleated melts are determined in order to assess the influence
      of the nucleating agents. Then spinning tests are carried out. Thermal and
      textile properties of the spun PHB fibers are also determined. An estimation of
      the improvement of inhibition of the secondary crystallization from use of the
      described blood compatible nucleating agents is given.

PMID- 16967478
TI  - Structure of algal-born phenolic polymeric adhesives.
AB  - Adhesive materials extracted from the brown alga Fucus serratus are composed of
      phenolic polymer, alginate, and CaCl2. The phenolic polymer undergoes an
      oxidation reaction in the presence of bromoperoxidase, KI, and H2O2. The
      nanostructure of the adhesive was investigated using small angle X-ray
      scattering, light scattering, and cryo- transmission electron microscopy
      experiments. These have shown that the phenolic polymer undergoes self-assembly
      and forms flexible chain-like objects. Oxidation or adding alginate does not
      alter this structure. However, once calcium ions are added, a rigid network is
      formed. Presumably, this network is responsible for the cohesive strength of the
      glue.

PMID- 16967479
TI  - Solvent-assisted room-temperature compression molding approach to fabricate
      porous scaffolds for tissue engineering.
AB  - This study investigated the room-temperature compression molding/particle
      leaching approach to fabricate three-dimensional porous scaffolds for tissue
      engineering. Scaffolds with anatomical shapes (ear, joint, tube, cylinder) were
      made from biodegradable poly(D,L-lactide) and poly[(D,L-lactide)-co-glycolide].
      The utility of this room-temperature compression approach comes from the effect
      of solvent assistance, but the tendency for post-molding scaffold shrinkage is a
      problem unique to this method and is thus examined with emphasis in this paper.
      Scaffold shrinkage was found to be tolerable under normal fabrication conditions
      with high salt contents, which is just what the preparation of highly porous
      scaffolds requires. Furthermore, the resultant porosities after salt leaching
      were measured as well as the initial scaffold shrinkages after solvent
      evaporation, and the relation between them was revealed by theoretical analysis
      and confirmed by comparison with experimental measurements. The pores were
      interconnected, and porosity can exceed 90%. The effects of porosity on the
      mechanical properties of porous scaffolds were also investigated. This convenient
      fabrication approach is a prospective method for the tailoring of porous
      scaffolds for a variety of possible applications in tissue engineering and tissue
      reconstruction.

PMID- 16967480
TI  - Loading and release of ibuprofen in multi- and monofilament surgical sutures.
AB  - The preparation of mono- and multifilament sutures incorporating ibuprofen as an
      anti-inflammatory agent is considered. Poly(p-dioxanone) monofilament samples can
      be loaded by a molecular diffusion process using a swelling agent such as
      dichloromethane. The mechanical properties have been measured and have not shown
      a significant change for the ibuprofen loaded samples in knot tensile assays. The
      kinetics of both the loading process and the release in a Sorensen's medium at 37
      degrees C have been investigated. Diffusion coefficients have also been estimated
      from film and slab poly(p-dioxanone) samples containing ibuprofen and their
      release behavior compared to that shown by monofilaments. Release from a coating
      copolymer based on lactide, epsilon-caprolactone and trimethylene carbonate
      (PLA/PCA/PTMC 10/60/30) has also been studied. This coating solubilizes ibuprofen
      molecules well and can be used for braided sutures or when a rapid dose of
      ibuprofen is preferred.

PMID- 16967481
TI  - Phase transition behavior of novel pH-sensitive polyaspartamide derivatives
      grafted with 1-(3-aminopropyl)imidazole.
AB  - New pH-sensitive polyaspartamide derivatives were synthesized by grafting 1-(3
      aminopropyl)imidazole and/or O-(2-aminoethyl)-O'-methylpoly(ethylene glycol) 5000
      on polysuccinimide for application in intracellular drug delivery systems. The DS
      of 1-(3-aminopropyl)imidazole was adjusted by the feed molar ratio, and the
      structure of the prepared polymer was confirmed using FT-IR and 1H NMR
      spectroscopy. Their pH-sensitive properties were characterized by light
      transmittance measurements, and the particle size and its distribution were
      investigated by dynamic light scattering measurements at varying pH values. The
      pH-sensitive phase transition was clearly observed in polymer solutions with a
      high substitution of 1-(3-aminopropyl)imidazole. The prepared polymers showed a
      high buffering capacity between pH 5 and 7, and this increased with the DS of 1
      (3-aminopropyl)imidazole. The pH dependence of the aggregation and de-aggregation
      behavior was examined using a fluorescence spectrometer. For MPEG/imidazole-g
      polyaspartamides with a DS of 1-(3-aminopropyl)imidazole over 82%, self
      aggregates associated with the hydrophobic interactions of the unprotonated
      imidazole groups were observed at pH values above 7, and their mean size was over
      200 nm, while the aggregates of polymers were dissociated at pH values below 7 by
      the protonation of imidazole groups. These pH-sensitive polyaspartamide
      derivatives are potential basic candidates for intracellular drug delivery
      carriers triggered by small pH changes.

PMID- 16967482
TI  - Micromechanical testing of individual collagen fibrils.
AB  - A novel method based on AFM was used to attach individual collagen fibrils
      between a glass surface and the AFM tip, to allow force spectroscopy studies of
      these. The fibrils were deposited on glass substrates that are partly coated with
      Teflon AF. A modified AFM tip was used to accurately deposit epoxy glue droplets
      on either end of the collagen fibril that cross the glass-Teflon AF interface, as
      to such attach it with one end to the glass and the other end to the AFM tip.
      Single collagen fibrils have been mechanically tested in ambient conditions and
      were found to behave reversibly up to stresses of 90 MPa. Within this regime a
      Young's modulus of 2-7 GPa was obtained. In aqueous media, the collagen fibrils
      could be tested reversibly up to about 15 MPa, revealing Young's moduli ranging
      from 0.2 to at most 0.8 GPa.

PMID- 16967483
TI  - Elastic, superporous hydrogel hybrids of polyacrylamide and sodium alginate.
AB  - A novel approach was developed to prepare a superporous hydrogel with superior
      mechanical and elastic properties. According to this method, a synthetic monomer
      was polymerized and crosslinked in the presence of a water-soluble alginate
      polymer. Later in the process, the alginate part of the synthesized hydrogel was
      treated with metal cations, which resulted in a hydrogel hybrid with an
      interpenetrating network structure. In this article, a hydrogel hybrid of
      acrylamide and alginate is highlighted because of its unique swelling and
      mechanical properties. This hydrogel hybrid shows resilience and a rubbery
      property in its fully water-swollen state, which not previously been reported. To
      help understand the underlying mechanism responsible for such unique properties
      with hydrogel hybrids, the ionotropic gelation of the alginate polymer was also
      studied in more detail.

PMID- 16967484
TI  - Effects of SCA1, MJD, and DPRLA triplet repeat polymorphisms on cognitive
      phenotypes in a normal population of adolescent twins.
AB  - The expansion of unstable trinucleotide CAG repeat polymorphisms of a number of
      genes causes several neurodegenerative disorders with decreased cognitive
      function, the severity of the disorder being related to allele length at the
      triplet repeat locus. While the effects of repeat length have been well studied
      in clinical samples, there has been little investigation of the effects of
      triplet repeat variation in the normal range for these genes. We have, therefore,
      examined linkage and association for three CAG triplet repeat markers
      (Spinocerebellar Ataxia Type 1, SCA1; Machado-Joseph Disease, MJD; Dentatorubro
      pallidoluysian Atrophy, DRPLA) to assess their contribution to variation in
      cognitive ability (IQ, reading ability, processing speed) in a normal, unselected
      sample of adolescent twins (248 dizygotic (DZ) sibling pairs, aged 16 years).
      Association tests, performed in Mx and QTDT, showed a consistent positive
      association of SCA1 with Arithmetic (P = 0.04). While association was supported
      between SCA1 and Cambridge reading scores and between DRPLA and inspection time,
      results were inconsistent across software packages. Given the number of
      statistical tests performed, it is unlikely that trinucleotide repeat variation
      in the normal range for these genes influences variation in normal cognition.

PMID- 16967485
TI  - Celiac disease and antibodies associated with celiac disease in patients with
      inflammatory myopathy.
AB  - Celiac disease is usually associated with autoimmune disorders and has
      occasionally been reported in patients with inflammatory myopathies. Our aim was
      to determine the presence of celiac disease and antibodies associated with celiac
      disease in patients with inflammatory myopathies and to investigate their
      relationship. Serum antigliadin, anti-tissue transglutaminase, and antiendomysial
      antibodies were determined in 51 patients with inflammatory myopathies. HLA-DQ2
      and -DQ8 alleles were studied to assess their complementary diagnostic value.
      Jejunal biopsy was performed in patients with moderate to high levels of
      antigliadin antibodies. Patients with jejunal histology consistent with celiac
      disease initiated a gluten-free diet. Seventeen patients (31%) were positive for
      antigliadin antibodies, which were significantly more frequent in patients with
      inclusion-body myositis than dermatomyositis (P < 0.001). Positive status to HLA
      DQ2 and/or -DQ8 did not differ between antigliadin-positive (75% and 12.5%) or 
      negative (60% and 15%) patients. Three of five jejunal biopsies were diagnostic
      for celiac disease with histological normalization after a gluten-free diet.
      Thus, celiac disease is more prevalent in patients with inflammatory myopathies
      than in the general population. Positive status to HLA-DQ2 allele, which is known
      to be more frequent in patients with inflammatory myopathies, could explain the
      high prevalence of antigliadin antibodies in this population. The diagnostic
      value of HLA-DQ2 or -DQ8 haplotypes to detect celiac disease in patients with
      inflammatory myopathy is limited.

PMID- 16967486
TI  - Plectin defects in epidermolysis bullosa simplex with muscular dystrophy.
AB  - Epidermolysis bullosa simplex with muscular dystrophy (EBS-MD, MIM 226670) is
      caused by plectin defects. We performed mutational analysis and
      immunohistochemistry using EBS-MD (n = 3 cases) and control skeletal muscle to
      determine pathogenesis. Mutational analysis revealed a novel homozygous plectin
      exon32 rod domain mutation (R2465X). All plectin/HD1-121 antibodies stained the
      control skeletal muscle membrane. However, plectin antibodies stained the
      cytoplasm of type II control muscle fibers (as confirmed by ATPase staining),
      whereas HD1-121 stained the cytoplasm of type I fibers. EBS-MD samples lacked
      membrane (n = 3) but retained cytoplasmic HD1-121 (n = 1) and plectin staining in
      type II fibers (n = 3). Ultrastructurally, EBS-MD demonstrated widening and
      vacuolization adjacent to the membrane and disorganization of Z-lines (n = 2 of
      3) compared to controls (n = 5). Control muscle immunogold labeling colocalized
      plectin and desmin to filamentous bridges between Z-lines and the membrane that
      were disrupted in EBS-MD muscle. We conclude that fiber-specific plectin
      expression is associated with the desmin-cytoskeleton, Z-lines, and crucially
      myocyte membrane linkage, analogous to hemidesmosomes in skin.

PMID- 16967487
TI  - Proapoptotic factor Bax is increased in satellite cells in the tibialis anterior
      muscles of old rats.
AB  - Aging impairs the ability of muscle to adapt to exercise or injury. The goal of
      this study was to determine whether age-related changes in muscle adaptability
      could be the result of satellite cell apoptosis. Ten days after exposure to an
      injury protocol, estimates of edema in the exposed tibialis anterior muscles were
      higher in old (30 months) than young (3 months) rats, and isometric force levels
      were lower in old rats. Both young and old rats displayed an increase in MyoD
      labeling in the exposed muscle, indicating that injury induced satellite-cell
      activation. However, there were more MyoD-labeled cells that coexpressed the
      proapoptotic factor, Bax, in old than in young rats, suggesting that decrements
      in muscle recovery may be associated with an increase in satellite-cell
      apoptosis. Based on these findings we conclude that reducing satellite-cell
      apoptosis in aged animals may improve muscle recovery after injury.

PMID- 16967488
TI  - Expanding the phenotypes of the Pro56Ser VAPB mutation: proximal SMA with
      dysautonomia.
AB  - The phenotype of 16 members of a family affected by a late-onset, dominant,
      progressive, motor and autonomic disorder is described. The VAPB (Pro56Ser)
      mutation was detected in Brazilian families with different phenotypes of motor
      neuron disorders. In this family, proximal and axial muscle weakness and atrophy,
      associated with abdominal protrusion, defined the motor phenotype. Death occurred
      in 10-15 years due to respiratory insufficiency. Tone and tendon reflexes were
      decreased and a distal tremor was common. Sensation was preserved. Autonomic
      abnormalities were also present, including choking, chronic intestinal
      constipation, sexual dysfunction, and sudomotor abnormalities, and on nerve
      morphology there was involvement of unmyelinated fibers. Electromyography
      disclosed ongoing denervation and reinnervation. Isolated dysfunction of motor
      and autonomic neurons is unusual among the spinal muscular atrophies. On this
      basis, this condition seems to represent a new category of disease.

PMID- 16967489
TI  - Predictability of disease progression in amyotrophic lateral sclerosis.
AB  - The aim of this study was to determine the predictors of disease progression in a
      group of 832 patients with the diagnosis of definite or probable amyotrophic
      lateral sclerosis (ALS). Disease progression was defined as the time to 20-point
      change in Appel ALS (AALS) score. The effects of individual prognostic factors on
      disease progression were assessed with the Kaplan-Meier life-table method. In
      addition, the prognostic value of each factor was estimated using both univariate
      and multivariate Cox proportional hazard analyses. The median time to a 20-point
      change in AALS score in our patient population was 9 months. Age, site of symptom
      onset, time between first symptom and first examination, total AALS score at
      first examination, and AALS preslope (rate of disease progression between first
      symptom and first examination) were significant and independent covariates of
      disease progression in our population. Identification of predictors of disease
      progression will facilitate better design of therapeutic trials, permitting the
      use of disease progression as a primary endpoint and improving baseline
      stratification of patient populations.

PMID- 16967490
TI  - Variable presentation of nemaline myopathy: novel mutation of alpha actin gene.
AB  - Nemaline myopathy is a rare disorder of varying severity and genetic etiology. We
      present two cases, a father and son, with a novel missense mutation in the alpha
      actin gene. Both have a history of early motor impairment, with the son's course
      being considerably more severe. This pair illustrates the clinical variability of
      nemaline myopathy, highlighting the possible influence of environmental and
      epigenetic factors. Implications for the current classification system and
      prognosis are discussed.

PMID- 16967491
TI  - Hip joint position modulates volitional knee extensor muscle activity after
      stroke.
AB  - Evidence from animal and human models has demonstrated the importance of hip
      proprioceptors and vestibular inputs in modulating lower-extremity muscle
      activity through reflex pathways. Comprehension of the role of these sensory
      inputs following stroke may be important in understanding pathological muscle
      activity during functional activities. We therefore examined the influence of
      both hip and head/trunk position on volitional quadriceps activity in chronic
      stroke and control subjects. With the knee held at 60 degrees, maximal voluntary
      isometric quadriceps contractions were elicited with trunk orientation (head
      position) and hip angle systematically positioned at 0 degrees, 45 degrees, and
      90 degrees. Integrated electromyographic activity from the quadriceps was
      compared between groups and conditions. Vasti activity in the stroke group was
      greater in a seated upright posture (hip flexed) than supine (hip neutral).
      Controlling for vestibular input, the stroke group demonstrated greater
      quadriceps activity (VL and RF) with a neutral hip compared to flexion. Such
      findings may have implications for understanding inappropriate muscle activity
      during walking after stroke, as hip extension occurs immediately prior to toe
      off, when inappropriate quadriceps activity is commonly observed.

PMID- 16967492
TI  - Rituximab treatment in patients with IVIg-dependent immune polyneuropathy: a
      prospective pilot trial.
AB  - We studied the effect of rituximab in allowing a reduction in dose of intravenous
      immune globulin (IVIg) in six patients with IVIg-dependent, relapsing immune
      polyneuropathy. Rituximab (375 mg/m(2) intravenously each week for 4 weeks) was
      administered in a prospective, open-label design to two patients with chronic
      inflammatory demyelinating polyneuropathy (CIDP), two with multifocal motor
      neuropathy (MMN), one with neuropathy and anti-myelin-associated glycoprotein
      (MAG) antibody neuropathy, and one with Sjogren syndrome (SS) ataxic neuropathy.
      The primary endpoint was a reduced cumulative IVIg dosage by at least 25% at 1
      year after rituximab therapy compared to the previous year. Secondary endpoints
      included an improved summed strength score by at least 5 points on the Medical
      Research Council scale, an increased sensory score by at least 4 points, or an
      improved Rankin disability score by at least 1 grade. Total IVIg dosage decreased
      by greater than 25% in one patient with SS neuropathy and one with MMN; the
      dosage was unchanged in one with CIDP, slightly reduced in the patient with anti
      MAG neuropathy, and increased in one with CIDP and another with MMN. There was no
      improvement in secondary endpoints. No adverse events occurred. In this small
      prospective study, rituximab did not reduce IVIg requirements in the majority of
      patients with IVIg-dependent, immune-mediated polyneuropathies.

PMID- 16967493
TI  - Laser scanning cytometry in the characterization of the proapoptotic effects of
      transiently transfected genes in cerebellar granule neurons.
AB  - BACKGROUND: Low transient transfection efficiency limits the ability to
      characterize putative proapoptotic gene function in neurons. Laser scanning
      cytometry (LSC), with its high capacity, medium throughput means of collecting
      fluorescent emissions from cultured cells, offers an effective technology for
      scoring cell death in neuronal transfectants. METHODS: Cerebellar granule neurons
      (CGNs) were transfected with EGFP-fusion constructs of Caspase-3 and Caspase-9
      using a DNA-calcium phosphate coprecipitation method. CGNs were fixed,
      permeablized, and stained with propidium iodide (PI) nuclear dye. An LSC method,
      based on a combination of Long Red Max Pixel, Long Red Integral, and Green
      Integral fluorescence parameters was validated for the scoring of apoptotic cell
      death in CGNs. RESULTS: In Caspase-3 and Caspase-9 transfected CGNs, cell death
      was scored both in transfectants and nontransfected culture-mates. The cell death
      phenotype was found to be independent of transfection efficiency. LSC scoring of
      Caspase-9 transfectants was compared with visual scoring following Hoechst 33342
      staining, yielding results that were similar qualitatively, but not
      quantitatively, likely owing to the greater sensitivity to green fluorescence of
      laser scanning compared to human vision. CONCLUSION: LSC scoring of transiently
      transfected CGNs offers a rapid and reliable means of characterizing proapoptotic
      gene effects.

PMID- 16967494
TI  - Comparison of fluorescein and phycoerythrin conjugates for quantifying CD20
      expression on normal and leukemic B-cells.
AB  - BACKGROUND: Numerous methods for quantitative fluorescence calibration (QFC) have
      been developed to quantify receptor expression on lymphocytes as potential
      disease biomarkers. CD20 expression in B-cell chronic lymphocytic leukemia (B
      CLL) is one of the best examples of such a biomarker, but results from the use of
      different QFC methods vary considerably. METHODS: We measured CD20 expression on
      normal and B-CLL B-cells, using FITC and PE conjugates from the same monoclonal
      antibody (Mab). As a biological control and calibrator, we also measured CD4
      expression on T-cells with FITC and PE Mab. Calibration curves were constructed
      using the CLSI (formerly NCCLS) consensus guidelines for QFC. Calibration with
      QuantiBRITE PE-labeled microspheres and the use of unimolar PE conjugates
      provided direct measurement of antibody bound per cell (ABC) for CD4 and CD20.
      Calibration for FITC conjugates was based on molecules of equivalent soluble
      fluorochrome (MESF), as determined by NIST RM 8640 microsphere standards. These
      MESF values were then converted to ABC, using the CD4 T-cell as a biologic
      calibrator, to normalize FITC and PE results for CD20 expression. RESULTS: On
      normal B cells, the mean ABC value for unimolar CD20-PE conjugate was 143,500 (CV
      +/- 19.1%). The mean ABC value for B-CLL B-cells stained with the same conjugate
      was 21,700 (CV +/- 42.0%). Using the CD4 T-cell as a biologic calibrator for FITC
      conjugate, the mean ABC value for CD20-FITC on normal B-cells was 199,300. CD20
      FITC staining on B-CLL cells was generally too weak for accurate quantification.
      On normal T-cells, the mean ABC value for CD4 unimolar PE conjugate was (36,800
      +/- 10.4)%, and it did not differ significantly in CLL samples. CONCLUSION: The
      expression of CD20 on normal and B-CLL lymphocytes can be quantified in ABC units
      using unimolar CD20-PE conjugates. In addition, CD4 expression on T-cells can be
      used as a biological calibrator to quantify CD20-FITC ABC, with reasonable
      agreement between the two conjugates with different fluorochromes. Issues
      regarding the accuracy of MESF microsphere calibrators and effective F/P ratios
      for FITC conjugates will require additional laboratory studies.

PMID- 16967495
TI  - Molecular and cellular defects of skeletal muscle in an animal model of acute
      quadriplegic myopathy.
AB  - Muscle denervation and concomitant high-dose dexamethasone treatment in rodents
      produces characteristic pathologic features of severe muscle atrophy and
      selective myosin heavy filament (MyHC) depletion, identical to those seen in
      acute quadriplegic myopathy (AQM), also known as critical illness myopathy. We
      tested the hypothesis that defective pre-translational processes contribute to
      the atrophy and selective MyHC depletion in this model. We examined the effects
      of combined glucocorticoid-denervation treatment on MyHC and actin mRNA
      populations; we also studied mRNA expression of the myogenic regulatory factors
      (MRFs), primary transcription factors for MyHC. Adult female rats were subjected
      to proximal sciatic denervation followed by high-dose dexamethasone (DD)
      treatment (5 mg/kg body weight daily) for 7 days. Disease controls included rats
      treated with denervation alone (DN) or dexamethasone alone (DX). At 1 week the
      plantaris atrophied by approximately 42% in DD muscles. DD treatment resulted in
      selective MyHC protein depletion; actin protein concentration was not
      significantly changed. Despite an increase in total RNA concentration in DN and
      DD muscles, MyHC and actin mRNA concentrations were significantly decreased in
      these muscles. MyHC mRNA showed a significantly more extensive depletion relative
      to actin mRNA in DD muscles. Glucocorticoid treatment did not influence a
      denervation-induced increase in the mRNA expression of the MRFs. We conclude that
      a deleterious interaction between glucocorticoid and denervation treatments in
      skeletal muscle is responsible for pre-translational defects that reduce actin
      and MyHC mRNA substrates in a disproportionate fashion. The resultant selective
      MyHC depletion contributes to the severe muscle atrophy.

PMID- 16967496
TI  - Whipple's disease with muscle impairment.
AB  - A 67-year-old man presented with myalgia, muscle atrophy, and a history of
      seronegative polyarthritis. Blood tests showed inflammation but no hematologic or
      immunologic abnormalities. Muscle biopsy revealed no vasculitis or myositis but
      Tropheryma whipplei was detected by polymerase chain reaction in muscle, blood,
      and duodenum specimens; this was confirmed by immunohistochemistry. Ceftriaxone
      led to clinical improvement. Although rare, Whipple's disease should be
      considered in the differential diagnosis of diffuse myopathy.

PMID- 16967497
TI  - Microinjection of carbachol in the supramammillary region suppresses CA1
      pyramidal cell synaptic excitability.
AB  - Previous studies have established that the posterior hypothalamus-supramammillary
      (SUM) region is involved in the control of the hippocampal theta rhythm and also
      modulates the synaptic excitation of hippocampal neurons. Particularly, the
      medial but not lateral SUM region mediates reticular stimulation-induced
      suppression of CA1 pyramidal cell synaptic excitation to Schaffer collateral
      stimulation. In the present study using urethane anesthetized rats, we have
      investigated the effect of direct chemical stimulation of the posterior
      hypothalamus-SUM region on CA1 pyramidal cell excitability. It was observed that
      microinjection of the cholinergic muscarinic receptor agonist, carbachol (0.1
      microl, concentration of either 0.0052, 0.156, or 0.625 microg/microl), evoked
      concentration-dependent suppression of CA1 pyramidal cell excitability that was
      dissociated from theta activation. Further, carbachol microinjection
      preferentially recruited the lateral SUM region when compared with the medial SUM
      and the posterior hypothalamic regions. In this context, the shortest latencies
      to suppression at the lowest concentration of carbachol and the strongest
      suppression at higher concentrations were observed with lateral microinjections.
      The carbachol-induced suppression was attenuated by inactivation of the medial
      septal region by microinjection of procaine (0.5 microl, 20% w/v). These results
      underscore a possible role for cholinergic mechanisms in the lateral SUM region
      in modulation of CA1 pyramidal cell synaptic excitation via the medial septal
      region. Furthermore, the present findings when juxtaposed with the medial SUM
      mediation of reticularly-elicited suppression suggest a medial-lateral
      topographic organization of the SUM region in modulation of CA1 excitability.

PMID- 16967498
TI  - High iNOS mRNA and protein levels during early third trimester suggest a role for
      NO in prelabor cervical ripening in the bovine.
AB  - Nitric oxide (NO) plays a key role in the processes leading to cervical softening
      prior to labor. Inducible nitric oxide synthase (iNOS) contributes most to the
      increased production of NO during labor, as demonstrated in the rat cervix, or at
      term pregnancy in women. Changes in expression of iNOS during late gestation have
      not yet been studied longitudinally in any species, because repeatedly taking
      biopsies could not be performed. iNOS mRNA (n = 6) and protein expression (n = 3)
      in serial cervical biopsies of pregnant pluriparous cows taken around days 225,
      250, and 275 of pregnancy and within 1.5 hr after calving (d225, d250, d275 and
      parturition biopsies, respectively) were measured using quantitative RT-PCR and
      Western blotting. iNOS mRNA expression decreased from the d225 biopsy onwards,
      differences being significant between the d250 and d275 (P < 0.05) and between
      the d275 and parturition biopsies (P < 0.05). iNOS protein expression decreased
      from d225 to d250 onwards. Immunohistochemical analysis of biopsies showed,
      besides positive staining in endothelium and epithelium, which remained unchanged
      at different time points, that iNOS expressing cells in the connective tissue
      cells of early biopsies were predominantly spindle shaped (mostly smooth muscle
      cells and some fibroblasts). In the parturition biopsies, iNOS reactivity was
      mainly found in mononuclear leucocytes. These results lead us to suggest that
      iNOS from spindle shaped cells is involved in prepartum cervical ripening, while
      iNOS in mononuclear inflammatory cells may be important for local tissue repair
      mechanisms during postpartum cervical involution.

PMID- 16967499
TI  - Premature translation of transition protein 2 mRNA causes sperm abnormalities and
      male infertility.
AB  - During mammalian spermiogenesis somatic histones are replaced at first by
      transition proteins, which are in turn replaced by the protamines, forming the
      sperm nucleoprotamines. It is believed that transition protein 2 (Tnp2) is
      necessary for maintaining the normal processing of protamines and, consequently,
      the completion of chromatin condensation. The transition protein mRNAs are stored
      in translationally inert messenger ribonucleoprotein particles for up to 7 days
      until translational activation in elongated spermatids. Substantial evidence
      suggests an involvement of 3'untranslated region (UTR) in the translational
      regulation of the Tnp2 mRNAs. In order to determine the role of Tnp2 3'UTR in
      translational regulation and to study whether the translational repression of
      Tnp2 mRNA is necessary for normal spermatid differentiation in mice, we generated
      transgenic mice that carry a Tnp2-hGH transgene. In this transgene, 3'UTR of Tnp2
      gene was replaced by 3' 3'UTR of human growth hormone gene. In these transgenic
      animals, transcription and translation of Tnp2 occur simultaneously in round
      spermatids which is an evidence for involvement of Tnp2 3'UTR in its translation
      repression. Premature translation of Tnp2 mRNA caused abnormal head
      morphogenesis, reduced sperm motility and male infertility. These results show
      clearly that a strict temporal and stage-specific Tnp2 translation is necessary
      for the correct differentiation of round spermatids into mature spermatozoa and
      for male fertility.

PMID- 16967500
TI  - Synergistic induction of apoptosis in primary rat decidual cells by INF-gamma and
      TNF.
AB  - In the rat, in response to blastocyst implantation, stromal cells of the
      endometrium proliferate and differentiate into decidual cells, forming the
      decidua. After reaching its maximum development, the decidua undergoes
      regression. This phenomenon appears to be due to an active process involving
      apoptosis. As there is sparse knowledge concerning the mechanisms of induction of
      decidual cell death, the potential role of cytokines present in the uterine
      environment during pregnancy, such as tumor necrosis factor (TNF) and interferon
      gamma (INF-gamma) was explored in primary cultures of rat decidual cells. The
      effects of these factors upon cellular viability, nuclear morphologic
      alterations, expression, and enzymatic activities of the effector caspases-3/7
      were evaluated. The results obtained demonstrated that in contrast to TNF, which
      did not induce any alteration, INF-gamma and in association with TNF caused a
      decrease in cell viability and an increase in the appearance of apoptotic bodies
      in a time-dependent manner that was augmented in the co-presence of TNF. An
      increase in caspase-3/7 activities after 12 hr of TNF/INF-gamma treatment was
      also observed. These findings suggest that INF-gamma expressed in the uterine
      environment may play an important role in regulating apoptosis through potential
      synergistic mechanisms with TNF and thereby modulate decidual stability and
      regression during pregnancy.

PMID- 16967501
TI  - Structural abnormalities in spermatids together with reduced sperm counts and
      motility underlie the reproductive defect in HIP1-/- mice.
AB  - Huntingtin interacting protein 1 (HIP1) is an endocytic adaptor protein with
      clathrin assembly activity that binds to cytoplasmic proteins, such as F-actin,
      tubulin, and huntingtin (htt). To gain insight into diverse functions of HIP1, we
      characterized the male reproductive defect of HIP1(-/-) mice from 7 to 30 weeks
      of age. High levels of HIP1 protein were expressed in the testis of wild-type
      mice as seen by Western blots and as a reaction over Sertoli cells and elongating
      spermatids as visualized by immunocytochemistry. Accordingly, major structural
      abnormalities were evident in HIP1(-/-) mice with vacuolation of seminiferous
      tubules caused by an apparent loss of postmeiotic spermatids and a significant
      reduction in mean profile area. Remaining spermatids revealed deformations of
      their heads, flagella, and/or acrosomes. In some Sertoli cells, ectoplasmic
      specializations (ES) were absent or altered in appearance accounting for the
      presence of spherical germ cells in the epididymal lumen. Quantitative analyses
      of sperm counts from the cauda epididymidis demonstrated a significant decrease
      in HIP1(-/-) mice compared to wild-type littermates. In addition, computer
      assisted sperm analyses indicated that velocities, amplitude of lateral head
      displacements (ALH), and numbers and percentages of sperm in the motile, rapid,
      and progressive categories were all significantly reduced in HIP1(-/-) mice,
      while the numbers and percentages of sperm in the static category were greatly
      increased. Taken together, these various abnormalities corroborate reduced
      fertility levels in HIP1(-/-) mice and suggest a role for HIP1 in stabilizing
      actin and microtubules, which are important cytoskeletal elements enabling normal
      spermatid and Sertoli cell morphology and function.

PMID- 16967502
TI  - Transition of nuclear proteins and chromatin structure in spermiogenesis of Sepia
      officinalis.
AB  - During spermiogenesis of Sepia officinalis histones are directly substituted by a
      molecule of precursor protamine, which is later transformed into the protamine
      through a deletion of the amino terminal end. In the present work, it is shown
      that the pattern of spermiogenic chromatin condensation consists of a phase of
      "patterning" and a phase of "condensation." In the phase of patterning, three
      structural remodelings are produced in the chromatin structure: [somatic-like
      chromatin --> 18 nm granules --> 25 nm fibers --> 44 nm fibers]. The first
      remodeling of the chromatin into granules of 18 nm takes place without the
      entrance of specific proteins in the spermiogenic nuclei. The second remodeling
      [granules of 18 nm --> fibers of 25 nm] is due to the entrance of the precursor
      protamine and its interaction with the DNA-histone complex. The third remodeling
      [fibers of 25 nm --> fibers of 44 nm] occurs simultaneously with the
      disappearance of histones from the chromatin. In the phase of condensation, the
      fibers of 44 nm coalesce among themselves to form progressively larger aggregates
      of chromatin. In this phase there are no substantial variations in the nuclear
      proteins, so that the condensation of the chromatin must respond to
      posttranscriptional changes of the precursor protamine (dephosphorylation,
      deletion of the amino-terminal end).

PMID- 16967503
TI  - Tissue inhibitor of metalloproteinase-2 (TIMP-2) regulates neuromuscular junction
      development via a beta1 integrin-mediated mechanism.
AB  - Extracellular matrix (ECM) molecules play critical roles in muscle function by
      participating in neuromuscular junction (NMJ) development and the establishment
      of stable, cytoskeleton-associated adhesions required for muscle contraction.
      Matrix metalloproteinases (MMPs) are neutral endopeptidases that degrade all ECM
      components. While the role of MMPs and their inhibitors, the tissue inhibitor of
      metalloproteinases (TIMPs), has been investigated in many tissues, little is
      known about their role in muscle development and mature function. TIMP-2 -/- mice
      display signs of muscle weakness. Here, we report that TIMP-2 is expressed at the
      NMJ and its expression is greater in fast-twitch (extensor digitorum longus, EDL)
      than slow-twitch (soleus) muscle. EDL muscle mass is reduced in TIMP-2-/- mice
      without a concomitant change in fiber diameter or number. The TIMP-2-/- phenotype
      is not likely due to increased ECM proteolysis because net MMP activity is
      actually reduced in TIMP-2-/- muscle. Most strikingly, TIMP-2 colocalizes with
      beta1 integrin at costameres in the wild-type EDL and beta1 integrin expression
      is significantly reduced in TIMP-2-/- EDL. We propose that reduced beta1 integrin
      in fast-twitch muscle may be associated with destabilized ECM-cytoskeletal
      interactions required for muscle contraction in TIMP-2-/- muscle; thus,
      explaining the muscle weakness. Given that fast-twitch fibers are lost in
      muscular dystrophies and age-related sarcopenia, if TIMP-2 regulates
      mechanotransduction in an MMP-independent manner it opens new potential
      therapeutic avenues.

PMID- 16967504
TI  - Intrastriatal administration of human immunodeficiency virus-1 glycoprotein 120
      reduces glial cell-line derived neurotrophic factor levels and causes apoptosis
      in the substantia nigra.
AB  - Uninfected neurons of the substantia nigra (SN) degenerate in human
      immunodeficiency virus (HIV)-positive patients through an unknown etiology. The
      HIV envelope glycoprotein 120 (gp120) causes apoptotic neuronal cell death in the
      rodent striatum, but its primary neurotoxic mechanism is still under
      investigation. Previous studies have shown that gp120 causes neurotoxicity in the
      rat striatum by reducing brain-derived neurotrophic factor (BDNF). Because glial
      cell line-derived neurotrophic factor (GDNF) and BDNF are neurotrophic factors
      crucial for the survival of dopaminergic neurons of the SN, we investigated
      whether gp120 reduces GDNF and BDNF levels concomitantly to induce apoptosis.
      Rats received a microinjection of gp120 or vehicle into the striatum and were
      sacrificed at various time intervals. GDNF but not BDNF immunoreactivity was
      decreased in the SN by 4 days in gp120-treated rats. In these animals, a
      significant increase in the number of caspase-3- positive neurons, both tyrosine
      hydroxylase (TH)-positive and -negative, was observed. Analysis of TH
      immunoreactivity revealed fewer TH-positive neurons and fibers in a medial and
      lateral portion of cell group A9 of the SN, an area that projects to the
      striatum, suggesting that gp120 induces retrograde degeneration of nigrostriatal
      neurons. We propose that dysfunction of the nigrostriatal dopaminergic system
      associated with HIV may be caused by a reduction of neurotrophic factor
      expression by gp120.

PMID- 16967505
TI  - Metalloprotease-induced ectodomain shedding of neural cell adhesion molecule
      (NCAM).
AB  - Transmembrane forms of neural cell adhesion molecule (NCAM140, NCAM180(1)) are
      key regulators of neuronal development. The extracellular domain of NCAM can
      occur as a soluble protein in normal brain, and its levels are elevated in
      neuropsychiatric disorders, such as schizophrenia; however the mechanism of
      ectodomain release is obscure. Ectodomain shedding of NCAM140, releasing a
      fragment of 115 kD, was found to be induced in NCAM-transfected L-fibroblasts by
      the tyrosine phosphatase inhibitor pervanadate, but not phorbol esters.
      Pervanadate-induced shedding was mediated by a disintegrin metalloprotease
      (ADAM), regulated by ERK1/2 MAP kinase. In primary cortical neurons, NCAM was
      shed at high levels, and the metalloprotease inhibitor GM6001 significantly
      increased NCAM-dependent neurite branching and outgrowth. Moreover, NCAM
      dependent neurite outgrowth and branching were inhibited in neurons isolated from
      a transgenic mouse model of NCAM shedding. These results suggest that regulated
      metalloprotease-induced ectodomain shedding of NCAM down-regulates neurite
      branching and neurite outgrowth. Thus, increased levels of soluble NCAM in
      schizophrenic brain have the potential to impair neuronal connectivity.

PMID- 16967506
TI  - Down-regulation of torp4a, encoding the Drosophila homologue of torsinA, results
      in increased neuronal degeneration.
AB  - Early-onset torsion dystonia is a dominant motor disorder linked to mutations in
      torsinA. TorsinA is weakly related to a superfamily of chaperone-like proteins.
      The function of the torsin group remains largely unknown. Here we use RNAi and
      over-expression to analyze the function of torp4a, the only Drosophila torsin.
      Targeted down-regulation in the eye causes progressive degeneration of the
      retina. Conversely, over-expression of torp4a protects from age-related
      degeneration. In the retinas of young animals, a correlation with the lysosome
      related organelle, the pigment granule, is also observed. Lowering torp4a causes
      an increase in pigment granules, while over-expression causes loss of granules.
      We have performed a screen for genetic interactors of torp4a identifying a number
      mutants, including two members of the AP-3 complex. Other genetic interactors
      found included genes related to actin and myosin function. Our findings implicate
      the Drosophila torsin, torp4a, to function with molecules consistent with already
      predicted roles in the endoplasmic reticulum/nuclear envelope compartment, and
      have identified potential new interactions with AP-3 like components.

PMID- 16967507
TI  - Breeding status affects motoneuron number and muscle size in naked mole-rats:
      recruitment of perineal motoneurons?
AB  - Naked mole-rats live in large colonies and exhibit a strict reproductive
      hierarchy. Each colony has one breeding female and one to three breeding males;
      all other individuals are nonreproductive subordinates. Subordinates show a
      remarkable lack of sex differences in behavior and anatomy, but can become
      reproductive if removed from the colony. We recently reported that the striated
      perineal muscles and their innervating motoneurons, which are sexually dimorphic
      in all other mammals examined to date, are not dimorphic in subordinate naked
      mole-rats. Here we asked whether sexual differentiation of this neuromuscular
      system occurs when a subordinate becomes a breeder. The size and number of cells
      within Onuf's nucleus (homologue of the rat spinal nucleus of the
      bulbocavernosus) as well as perineal muscle volume were examined in subordinate
      and breeding naked mole-rats of both sexes. Sex differences in perineal
      motoneurons were not observed, regardless of social status. To our surprise,
      however, counts of motoneurons in Onuf's nucleus were increased approximately 30%
      in breeders of both sexes. This was accompanied by a reciprocal decrease in cells
      in Onuf's nucleus that were characterized by small soma size, and lacked a clear
      nucleus or nucleolus. Although not exhibiting typical motoneuron morphology, some
      of these small cells were positive for the motoneuron marker, SMI-32. The
      neuronal changes correlate with increased perineal muscle volumes in breeders. We
      propose that small, relatively undifferentiated cells are recruited to the pool
      of large Onuf's nucleus motoneurons when subordinate naked mole-rats become
      breeders.

PMID- 16967508
TI  - Distinct functions of neuronal synaptobrevin in developing and mature fly
      photoreceptors.
AB  - Neuronal synaptobrevin (n-Syb, alias VAMP2), a synaptic vesicle membrane protein
      with a central role in neurotransmission, is specifically cleaved by the light
      chain of tetanus neurotoxin (TNT) that is known to reliably block
      neuroexocytosis. Here, we study fly photoreceptors transmitting continuous,
      graded signals to first order interneurons in the lamina, and report consequences
      of targeted expression of TNT in these cells using the UAS/GAL4 driver/effector
      system. Expressing the toxin throughout photoreceptor development causes
      developmental, electrophysiological, and behavioral defects. These can be
      differentiated by confining toxin expression to shorter developmental periods.
      Applying a method for controlled temporal and spatial TNT expression, we found
      that in the early pupa it impaired the development of the retina; in the midpupa,
      during synapse formation TNT caused a severe hypoplasia of the lamina that
      persisted into adulthood and left the photoreceptor-interneuron synapses of the
      lamina without function. Finally, during adulthood TNT neither blocks synaptic
      transmission in photoreceptors nor depletes the cells of n-Syb. Our study
      suggests a novel, cell type-specific function of n-Syb in synaptogenesis and it
      distinguishes between two synapse types: TNT resistant and TNT sensitive ones.
      These results need to be taken into account if TNT is used for neural circuit
      analysis.

PMID- 16967509
TI  - Reduction in nerve growth factor availability leads to a conditioning lesion-like
      effect in sympathetic neurons.
AB  - Axotomized peripheral neurons are capable of regeneration, and the rate of
      regeneration can be enhanced by a conditioning lesion (i.e., a lesion prior to
      the lesion after which neurite outgrowth is measured). A possible signal that
      could trigger the conditioning lesion effect is the reduction in availability of
      a target-derived factor resulting from the disconnection of a neuron from its
      target tissue. We tested this hypothesis with respect to nerve growth factor
      (NGF) and sympathetic neurons by administering an antiserum to NGF to adult mice
      for 7 days prior to explantation or dissociation of the superior cervical
      ganglion (SCG) and subsequently measuring neurite outgrowth. The antiserum
      treatment dramatically lowered the concentration of NGF in the SCG and increased
      the rate of neurite outgrowth in both explants and cell cultures. The increase in
      neurite outgrowth was similar in magnitude to that seen after a conditioning
      lesion. To determine if exogenous NGF could block the effect of a conditioning
      lesion, mice were injected with NGF or cytochrome C immediately prior to
      unilateral axotomy of the SCG, and for 7 days thereafter. A conditioning lesion
      effect of similar magnitude was seen in NGF-treated and control animals. While
      NGF treatment increased NGF levels in the contralateral control ganglion, it did
      not significantly elevate levels in the axotomized ganglion. The results suggest
      that the decreased availability of NGF after axotomy is a sufficient stimulus to
      induce the conditioning lesion effect in sympathetic neurons. While NGF
      administration did not prevent the conditioning lesion effect, this may be due to
      the markedly decreased ability of sympathetic neurons to accumulate the growth
      factor after axotomy.

PMID- 16967510
TI  - Pre-/post-otic rhombomeric interactions control the emergence of a fetal-like
      respiratory rhythm in the mouse embryo.
AB  - How regional patterning of the neural tube in vertebrate embryos may influence
      the emergence and the function of neural networks remains elusive. We have begun
      to address this issue in the embryonic mouse hindbrain by studying rhythmogenic
      properties of different neural tube segments. We have isolated pre- and post-otic
      hindbrain segments and spinal segments of the mouse neural tube, when they form
      at embryonic day (E) 9, and grafted them into the same positions in stage-matched
      chick hosts. Three days after grafting, in vitro recordings of the activity in
      the cranial nerves exiting the grafts indicate that a high frequency (HF) rhythm
      (order: 10 bursts/min) is generated in post-otic segments while more anterior pre
      otic and more posterior spinal territories generate a low frequency (LF) rhythm
      (order: 1 burst/min). Comparison with homo-specific grafting of corresponding
      chick segments points to conservation in mouse and chick of the link between the
      patterning of activities and the axial origin of the hindbrain segment. This HF
      rhythm is reminiscent of the respiratory rhythm known to appear at E15 in mice.
      We also report on pre-/post-otic interactions. The pre-otic rhombomere 5 prevents
      the emergence of the HF rhythm at E12. Although the nature of the interaction
      with r5 remains obscure, we propose that ontogeny of fetal-like respiratory
      circuits relies on: (i) a selective developmental program enforcing HF rhythm
      generation, already set at E9 in post-otic segments, and (ii) trans-segmental
      interactions with pre-otic territories that may control the time when this rhythm
      appears.

PMID- 16967512
TI  - Nephropathy and defective spermatogenesis in mice transgenic for a single isoform
      of the Wilms' tumour suppressor protein, WT1-KTS, together with one disrupted Wt1
      allele.
AB  - The Wilms' tumour suppressor protein, WT1, is a zinc finger protein essential for
      the development of several organs, including the kidney and gonads. In each of
      these tissues WT1 is required at multiple stages of development and its
      persistent expression in podocytes and Sertoli cells suggests WT1 may also have a
      role in the maintenance of kidney and testis function throughout adult life.
      Naturally occurring isoforms of WT1 are generated by alternative mRNA splicing.
      An altered ratio of the splice isoforms WT1-KTS and WT1 + KTS appears to be
      sufficient to account for the developmental abnormalities (pseudohermaphroditism
      and nephropathy) characteristic of Frasier syndrome. We show that mice with a
      transgene encoding WT1-KTS do not differ from their wild-type littermates unless
      they are also heterozygous for a null mutation at the endogenous Wt1 locus.
      Animals with both genetic modifications develop proteinuria, together with
      multiple glomerular cysts, and male infertility. These pathologic changes may be
      explained as a consequence of altering the WT1 isoform ratio in tissues that
      express WT1 during adulthood. The results suggest WT1 misexpression could
      contribute to human glomerulocystic kidney disease.

PMID- 16967511
TI  - Gbetagamma that interacts with adenylyl cyclase in opioid tolerance originates
      from a Gs protein.
AB  - We previously demonstrated that chronic morphine induces a change in G protein
      coupling by the mu opioid receptor (MOR) from Gi/o to Gs, concurrent with the
      instatement of an interaction between Gbetagamma and adenylyl cyclase types II
      and IV. These two signaling changes confer excitatory effects on the cell in
      place of the typical inhibition by opioids and are associated with morphine
      tolerance and dependence. Both signaling changes and these behavioral
      manifestations of chronic morphine are attenuated by cotreatment with ultra-low
      dose naloxone. In the present work, using striatum from chronic morphine-treated
      rats, we isotyped the Gbeta within Gs and Go heterotrimers that coupled to MOR
      and compared these to the Gbeta isotype of the Gbetagamma that interacted with
      adenylyl cyclase II or IV after chronic morphine treatment. Isotyping results
      show that chronic morphine causes a Gs heterotrimer associated with MOR to
      release its Gbetagamma to interact with adenylyl cyclase. These data suggest that
      the switch to Gs coupling by MOR in response to chronic morphine, which is
      attenuated by ultra-low-dose opioid antagonist cotreatment, leads to a two
      pronged stimulation of adenylyl cyclase utilizing both Galpha and Gbetagamma
      subunits of the Gs protein novel to this receptor.

PMID- 16967513
TI  - Simulation of an all-beta 3-icosapeptide containing the 20 proteinogenic side
      chains: effect of temperature, pH, counterions, solvent, and force field on helix
      stability.
AB  - Simulations of various beta-peptides have in the last years clarified several
      issues concerning peptide folding equilibria and interpretation of experimental
      data, especially from NMR and CD spectroscopy. These simulations involved
      different temperatures, pH-values, ionic strengths, solvents, and force-field
      parameters, but a variation of these factors for one beta-peptide has not yet
      been done. To investigate the influence of varying these factors, we analyze the
      helix stability of an all-beta3-icosapeptide bearing all 20 proteinogenic amino
      acid side chains, which is experimentally observed to fold into a 3(14)-helix in
      methanol but not in water. Structural aspects, such as hydrogen-bonded rings and
      salt bridges, are discussed and a comparison with NMR primary (NOE distance
      bounds and 3J-values) and secondary (NMR derived model structures) data is made.
      We further investigate the reasons for the 3(14)-helix stability/instability in
      methanol/water. Of all factors studied, the presence of counterions seems to be
      the one inducing most significant effects in the simulations.

PMID- 16967514
TI  - The importance of ingestion rates for estimating food quality and energy intake.
AB  - Testing ecological or socioecological models in primatology often requires
      estimates of individual energy intake. It is a well established fact that the
      nutrient content (and hence the energy content) of primate food items is highly
      variable. The second variable in determining primate energy intake, i.e., the
      ingestion rate, has often been ignored, and few studies have attempted to
      estimate the relative importance of the two predictors. In the present study
      individual ingestion rates were measured in two ecologically very different
      populations of Hanuman langurs (Semnopithecus entellus) at Jodhpur, India, and
      Ramnagar, Nepal. Protein and soluble sugar concentrations in 50 and 100 food
      items. respectively, were measured using standardized methods. Variation in
      ingestion rates (gram of dry matter per minute) was markedly greater among food
      items than among langur individuals in both populations, but did not differ
      systematically among food item categories defined according to plant part and
      age. General linear models (GLMs) with ingestion rate, protein, and soluble sugar
      content explained 40-80% of the variation in energy intake rates (kJ/min). The
      relative importance of ingestion rates was either similar (Ramnagar) or much
      greater (Jodhpur) than the role of sugar and/or protein content in determining
      the energy intake rates of different items. These results may impact
      socioecological studies of variation in individual energy budgets, investigations
      of food choice in relation to chemical composition or sensory characteristics,
      and research into habitat preferences that measures habitat quality in terms of
      abundance of important food sources. We suggest a definition of food quality that
      includes not only the amount of valuable food contents (energy, vitamins, and
      minerals) and the digestibility of different foods, but also the rate at which
      the food can be harvested and processed. Such an extended definition seems
      necessary because time may constrain primates when feeding competition is intense
      and foraging is risk-prone.

PMID- 16967515
TI  - Differential use of attentional and visual communicative signaling by orangutans
      (Pongo pygmaeus) and gorillas (Gorilla gorilla) in response to the attentional
      status of a human.
AB  - In this study we investigated the communicative abilities of 10 orangutans (Pongo
      pygmaeus) and seven western lowland gorillas (Gorilla gorilla gorilla), and
      particularly focused on their sensitivity to the attentional state of a human
      experimenter when choosing from a repertoire of both auditory and visual
      communication strategies. In experiment 1 a banana was placed in front of the
      subject's cage and a human experimenter was either present or absent. The
      subject's behavior was recorded for 60 sec. Both gorillas and orangutans gestured
      (t(16)=-3.58, P<.005) and vocalized (t(16)=-2.47, P<.05) more when the
      experimenter was present. In experiment 2 a human experimenter held a banana in
      front of the subject's cage and was oriented either toward or away from the
      subject. Again the subject's behavior was recorded for 60 sec. In this experiment
      both gorillas and orangutans gestured significantly more frequently (t(16)=3.40,
      P<.005) when the experimenter was oriented toward them. In addition, gorillas and
      orangutans used other forms of visual communication signals, such as lip pout
      (t(16)=3.66, P<.005), barter/trade (t(16)=2.31, P<.05), and body present
      (t(16)=2.31, P<.05) significantly more when an experimenter was facing them. The
      overall results indicate that both gorillas and orangutans are sensitive to the
      attentional state of a human experimenter and use appropriate communicative
      signals to gain that individual's attention. These results are also similar to
      previous findings on communicative behaviors in chimpanzees.

PMID- 16967516
TI  - Characterization and differential expression of vascular endothelial growth
      factor isoforms and receptors in swine corpus luteum throughout estrous cycle.
AB  - Corpus luteum (CL) undergoes growth and regression during each estrous cycle;
      these processes are accompanied by growth and regression of the luteal vascular
      bed. Vascular endothelial growth factor (VEGF) is the main regulator of
      angiogenesis, inducing endothelial cell proliferation, migration, vascular
      permeability, and vessel lumen formation. VEGF presents several isoforms that are
      produced by alternative splicing of the same mRNA transcript. We determined by
      real time RT-PCR the expression patterns of VEGF isoform and receptor mRNAs, as
      well as the VEGF protein levels in pig CL throughout a whole estrous cycle. Four
      novel VEGF isoforms (VEGF144, VEGF147, VEGF182, and VEGF164b) were found for the
      first time in swine and the seven identified isoforms can be grouped in four
      different patterns of expression. The most expressed splice variants were VEGF120
      and VEGF164. All isoforms showed their highest mRNA levels in newly formed CLs
      (day 1), followed by a decrease during mid-late luteal phase (days 10-17), except
      for VEGF182, VEGF188 and VEGF144 that showed a differential regulation during
      late luteal phase (day 14) or at luteolysis (day 17). VEGF protein levels
      paralleled the most expressed and secreted VEGF120 and VEGF164 isoforms. The VEGF
      receptors mRNAs showed a different pattern of expression in relation to their
      ligands, increasing between day 1 and 3 and gradually decreasing during the mid
      late luteal phase. The differential regulation of VEGF isoforms may suggest
      specific physiological roles for some of them, particularly in angioregression
      occurring during the apoptotic structural luteolysis.

PMID- 16967517
TI  - Regulation of MMP-9 expression and activity in the mouse uterus by estrogen.
AB  - Matrix metalloproteinases (MMPs) are spatiotemporally expressed in the uterus
      across normal estrous and menstrual cycles and are known to participate in the
      extensive endometrial tissue remodeling. MMP-9/gelatinase B is one of the major
      MMPs found in the uterus that modulates uterine biology during various
      reproductive processes. Although it seems that uterine MMP-9 is under ovarian
      steroid hormonal control, there are conflicting reports regarding steroidal
      hormonal regulation of MMP-9 expression, and there is little information on the
      effects of estrogen in vivo in this respect. We therefore examined the steroidal
      regulation of MMP-9 within the mouse uterus. Female mice (2-3 months old) were
      ovariectomized and treated with estradiol-l7beta (E(2)) or E(2) + progesterone
      (P(4)) and uterine gelatinase activity and expression were determined. Gelatin
      zymography revealed that E(2) alone or in combination with P(4) increased MMP-9
      activation, whereas Northern analysis showed that E(2) decreased MMP-9 steady
      state mRNA expression and an estrogen receptor antagonist ICI-182, 780 blocked
      this effect. In contrast, uterine MMP-2 expression and activity were not affected
      by steroidal treatments. Pretreatment with a transcription inhibitor actinomycin
      D or translation inhibitor cycloheximide indicates that E(2) regulates uterine
      MMP-9 at multiple points, involving transcriptional and posttranscriptional
      control as well as modulation of inhibitor activities. Collectively, these data
      suggest that E(2) regulates uterine MMP-9 expression and activity in vivo via a
      complex mechanism. This estrogen regulation of MMP-9 activity may play an
      important role in uterine tissue remodeling.

PMID- 16967519
TI  - Effect of cationic flaxseed protein hydrolysate fractions on the in vitro
      structure and activity of calmodulin-dependent endothelial nitric oxide synthase.
AB  - The objective of this study was to determine the in vitro effects of cationic
      flaxseed protein hydrolysate fractions on calmodulin (CaM) structure as well as
      the activity of CaM-dependent endothelial nitric oxide synthase (eNOS). Flaxseed
      protein isolate was hydrolyzed with alcalase, and two peptide fractions were
      isolated by cation-exchange chromatography. Fraction I, eluted first from the
      column, and fraction II contained 42% and 51% contents of basic amino acids,
      respectively. Fractions I and II reduced the activity of CaM-dependent eNOS
      through a mostly mixed-type inhibition mode. Fraction II was at least ten times
      more effective as an eNOS inhibitor when compared to fraction I, as evident from
      the IC(50) (concentration of protein hydrolysate that reduced eNOS activity by
      50%) values. Fluorescence spectroscopy showed that the tyrosine residues in CaM
      were increasingly exposed upon addition of fraction I, while the opposite was the
      case when fraction II was added. Circular dichroism studies showed that fractions
      I and II reduced the alpha-helix content but increased the rigidity of the active
      calcium/CaM complex. We concluded that ability of the protein hydrolysate
      fractions to change the secondary and tertiary structures of CaM may explain
      their ability to reduce activity of CaM-dependent eNOS.

PMID- 16967518
TI  - Molecular weight of guar gum affects short-chain fatty acid profile in model
      intestinal fermentation.
AB  - Dietary fiber exerts many beneficial physiological effects; however, not all
      types of dietary fiber display the same effects. Partially hydrolyzed guar gum
      (PHGG), a lower molecular weight form of guar gum, is more easily incorporated
      into food, but may have less pronounced physiological effects than the native
      form. The aim of this study was to identify differences in intestinal
      fermentability based on the molecular weight of guar gum. Guar gum of four
      molecular masses (15, 20, 400, and 1,100 kDa) was fermented using a batch in
      vitro fermentation system. Human fecal inoculum was the source of microbes. The
      400-kDa fraction produced the greatest concentrations of total short-chain fatty
      acid (SCFA) at 8 h and the highest amounts of butyrate at 24 h. At 24 h, the 400
      kDa fraction produced more total SCFA and propionate than the 15 kDa, but was not
      different than 20 kDa or 1,100 kDa fractions. The molecular weight of guar gum
      was positively correlated with acetate production and negatively correlated with
      propionate production. This study concludes that 400-kDa guar gum may be optimal
      for intestinal fermentability. In conclusion, the molecular weight of guar gum
      affects in vitro fermentability and should be considered when adding to a food or
      beverage.

PMID- 16967520
TI  - UK pushes stem cell support.

PMID- 16967521
TI  - [Buruli ulcer emerging from obscurity].

PMID- 16967522
TI  - Readers' and author's responses to "are traditional peer-reviewed medical
      articles obsolete?".

PMID- 16967523
TI  - Readers' and author's responses to "are traditional peer-reviewed medical
      articles obsolete?".

PMID- 16967524
TI  - Readers' and author's responses to "are traditional peer-reviewed medical
      articles obsolete?".

PMID- 16967525
TI  - [15th consensus conference about management of lower respiratory tract infections
      in immunocompetent adult].

PMID- 16967526
TI  - Readers' responses to the letter by Chalifoux and the editorial by Bond in regard
      to "sham peer review".

PMID- 16967527
TI  - Readers' responses to the letter by Chalifoux and the editorial by Bond in regard
      to "sham peer review".

PMID- 16967528
TI  - Readers' responses to the letter by Chalifoux and the editorial by Bond in regard
      to "sham peer review".

PMID- 16967529
TI  - Readers respond to "increasing diversity in the medical workforce is one solid
      way to prevent disparities in healthcare".

PMID- 16967530
TI  - Readers respond to "increasing diversity in the medical workforce is one solid
      way to prevent disparities in healthcare".

PMID- 16967531
TI  - Readers respond to "increasing diversity in the medical workforce is one solid
      way to prevent disparities in healthcare".

PMID- 16967532
TI  - Readers respond to "increasing diversity in the medical workforce is one solid
      way to prevent disparities in healthcare".

PMID- 16967533
TI  - Readers' responses to "MRI replaces CT for stroke evaluation".

PMID- 16967534
TI  - Readers' responses to "thought for food, part 2: a great weight-loss
      supplement?".

PMID- 16967535
TI  - Readers' responses to "thought for food, part 2: a great weight-loss
      supplement?".

PMID- 16967536
TI  - Readers' responses to "thought for food, part 2: a great weight-loss
      supplement?".

PMID- 16967537
TI  - Readers' responses to "thought for food, part 2: a great weight-loss
      supplement?".

PMID- 16967538
TI  - Readers' and author's responses to "are we really better off with HIPAA?".

PMID- 16967539
TI  - Readers' and author's responses to "are we really better off with HIPAA?".

PMID- 16967540
TI  - Readers' and author's responses to "are we really better off with HIPAA?".

PMID- 16967541
TI  - Readers' and author's responses to "are we really better off with HIPAA?".

PMID- 16967542
TI  - Readers' and author's responses to "are we really better off with HIPAA?".

PMID- 16967543
TI  - Readers' and author's responses to "are we really better off with HIPAA?".

PMID- 16967544
TI  - Readers' and author's responses to "are we really better off with HIPAA?".

PMID- 16967545
TI  - Readers' and author's responses to "are we really better off with HIPAA?".

PMID- 16967546
TI  - Readers' and author's responses to "are we really better off with HIPAA?".

PMID- 16967547
TI  - Readers' responses (continued) to "it is time for marijuana to be reclassified as
      something other than a schedule I drug".

PMID- 16967548
TI  - Readers' responses to "is there a place for medical blogs in a medical media
      company?".

PMID- 16967549
TI  - Readers' responses to "is there a place for medical blogs in a medical media
      company?".

PMID- 16967550
TI  - RNA interference on target.

PMID- 16967551
TI  - STEDy progress.
AB  - Continuing progress in the development of stimulated emission depletion
      microscopy (STED) is slowly but surely fulfilling the method's promise of
      ultrahigh-resolution fluorescence microscopy and may bring unexpected benefits to
      other imaging modalities as well.

PMID- 16967552
TI  - Quantum dots go with the flow.
AB  - Adding quantum dots to a repertoire of conventional fluorochromes allows
      researchers to extend the power of fluorescence immunophenotyping.

PMID- 16967553
TI  - In praise of manual high-throughput screening.
AB  - RNA interference (RNAi) and automated high-throughput screening is a promising
      combination. But the first systematic large-scale mapping of genetic interactions
      in an animal shows that manual methods still have advantages over sophisticated
      automated screens.

PMID- 16967554
TI  - Pushing size to the limit: extreme DNA.
AB  - Double-wide pyrimidine bases can assemble into helical, sequence-specific DNA
      complexes.

PMID- 16967555
TI  - Iraq's health requires continued funding commitment.

PMID- 16967556
TI  - Assessing the health implications of Nepal's ceasefire.

PMID- 16967557
TI  - Cover illustration. From the top down.

PMID- 16967558
TI  - Genetic mapping of the gene affecting polyphenol oxidase activity in tetraploid
      durum wheat.
AB  - The quality of durum wheat (Triticum turgidum ssp. durum) is influenced by
      polyphenol oxidase(PPO) activity and its corresponding substrates. A saturated
      molecular-marker linkage map was constructed previously by using a set of
      recombinant inbred (RI) lines, derived from a cross between durum wheat cultivars
      Jennah Khetifa and Cham 1. Quantitative trait loci (QTL) for PPO activity in
      seeds were mapped in this population. PPO activity in seeds of the parents and
      110 RI lines was measured spectrophotometrically. The PPO activity of Cham 1 was
      significantly lower than that of Jennah Khetifa. QTL analysis of these data
      indicated that most of PPO activity was associated with major loci on the long
      arm of chromosome 2A. The trait was found to be strongly associated with the SSR
      marker Xgwm312@2A. With this knowledge, marker-assisted selection can be used to
      select genotypes with lower PPO activity in durum wheat populations.

PMID- 16967559
TI  - [Depression--a public disease].

PMID- 16967560
TI  - [Physicians recruitment problems in psychiatry].

PMID- 16967561
TI  - 9-day payment freeze could turn into 12 days.

PMID- 16967562
TI  - The TG system for bedside recording of sputum colour.

PMID- 16967563
TI  - Another fallen super hero.

PMID- 16967564
TI  - Insurance. HSAs in crosshairs.

PMID- 16967565
TI  - The constitutionality of abortion on request in South Africa.

PMID- 16967566
TI  - For love or money: the legal regulation of surrogate motherhood.

PMID- 16967567
TI  - Judges' voices in the French abortion debate of the 1970s.

PMID- 16967568
TI  - Anisotropic imaging performance in indirect x-ray imaging detectors.
AB  - We report on the variability in imaging system performance due to oblique x-ray
      incidence, and the associated transport of quanta (both x rays and optical
      photons) through the phosphor, in columnar indirect digital detectors. The
      analysis uses MANTIS, a combined x-ray, electron, and optical Monte Carlo
      transport code freely available. We describe the main features of the simulation
      method and provide some validation of the phosphor screen models considered in
      this work. We report x-ray and electron three-dimensional energy deposition
      distributions and point-response functions (PRFs), including optical spread in
      columnar phosphor screens of thickness 100 and 500 microm, for 19, 39, 59, and 79
      keV monoenergetic x-ray beams incident at 0 degrees, 10 degrees, and 15 degrees.
      In addition, we present pulse-height spectra for the same phosphor thickness, x
      ray energies, and angles of incidence. Our results suggest that the PRF due to
      the phosphor blur is highly nonsymmetrical, and that the resolution properties of
      a columnar screen in a tomographic, or tomosynthetic imaging system varies
      significantly with the angle of x-ray incidence. Moreover, we find that the noise
      due to the variability in the number of light photons detected per primary x-ray
      interaction, summarized in the information or Swank factor, is somewhat
      independent of thickness and incidence angle of the x-ray beam. Our results also
      suggest that the anisotropy in the PRF is not less in screens with absorptive
      backings, while the noise introduced by variations in the gain and optical
      transport is larger. Predictions from MANTIS, after additional validation, can
      provide the needed understanding of the extent of such variations, and
      eventually, lead to the incorporation of the changes in imaging performance with
      incidence angle into the reconstruction algorithms for volumetric x-ray imaging
      systems.

PMID- 16967569
TI  - New questions emerge over stem-cell research claims.

PMID- 16967570
TI  - New 'air pollution alerts' warn of health risks.

PMID- 16967571
TI  - Free-energy landscape of alcohol driven coacervation transition in aqueous
      gelatin solutions.
AB  - Liquid-liquid phase separation of a homogeneous polyampholyte (gelatin) solution
      into a dense polymer-rich coacervate and the dilute supernatant phase is
      discussed through free-energy landscape formalism. We have evaluated the free
      energy and entropy of the system as it undergoes the phenomenon of simple
      coacervation, driven by the addition of a nonsolvent. Electrophoretic mobility
      (mu) and turbidity measurements were performed on 0.01% and 0.05% (w/v) aqueous
      gelatin solutions that were driven towards coacervation by the addition of
      ethanol. The mobility of the polyampholyte molecules, which was typically mu
      approximately 0.38+/-0.02 microm/s cm/V in water, gradually reduced for the
      soluble intermolecular complexes to a plateau value of mu approximately 0.11+/
      0.01 microm/s cm/V as the ethanol volume fraction equaled phi(ns) approximately
      0.47+/-0.03, which coincided with the first appearance of coacervate droplets
      (coacervation transition) observed from turbidity measurements, a behavior found
      to be invariant of gelatin concentration. These results were used as input to the
      theoretical model to explicitly construct the free-energy landscape for a single
      gelatin chain and the global system comprising the polymer-rich coacervate and
      the dilute supernatant phase.

PMID- 16967572
TI  - Erythropoietin and hepatitis C therapy: useful adjuvant therapy but remember to
      treat the patient and not just a number.

PMID- 16967576
TI  - A dreadful heritage: interpreting epidemic disease at Eyam, 1666-2000.

PMID- 16967577
TI  - Sequence-based species delimitation for the DNA taxonomy of undescribed insects.
AB  - Cataloging the very large number of undescribed species of insects could be
      greatly accelerated by automated DNA based approaches, but procedures for large
      scale species discovery from sequence data are currently lacking. Here, we use
      mitochondrial DNA variation to delimit species in a poorly known beetle radiation
      in the genus Rivacindela from arid Australia. Among 468 individuals sampled from
      65 sites and multiple morphologically distinguishable types, sequence variation
      in three mtDNA genes (cytochrome oxidase subunit 1, cytochrome b, 16S ribosomal
      RNA) was strongly partitioned between 46 or 47 putative species identified with
      quantitative methods of species recognition based on fixed unique ("diagnostic")
      characters. The boundaries between groups were also recognizable from a striking
      increase in branching rate in clock-constrained calibrated trees. Models of
      stochastic lineage growth (Yule models) were combined with coalescence theory to
      develop a new likelihood method that determines the point of transition from
      species-level (speciation and extinction) to population-level (coalescence)
      evolutionary processes. Fitting the location of the switches from speciation to
      coalescent nodes on the ultrametric tree of Rivacindela produced a transition in
      branching rate occurring at 0.43 Mya, leading to an estimate of 48 putative
      species (confidence interval for the threshold ranging from 47 to 51 clusters
      within 2 logL units). Entities delimited in this way exhibited biological
      properties of traditionally defined species, showing coherence of geographic
      ranges, broad congruence with morphologically recognized species, and levels of
      sequence divergence typical for closely related species of insects. The finding
      of discontinuous evolutionary groupings that are readily apparent in patterns of
      sequence variation permits largely automated species delineation from DNA surveys
      of local communities as a scaffold for taxonomy in this poorly known insect
      group.

PMID- 16967578
TI  - Importance of research design in cost analysis.

PMID- 16967579
TI  - High-dose subcutaneous midazolam infusions in palliative care.

PMID- 16967580
TI  - A randomized double-blind crossover trial of intravenous lidocaine in the
      treatment of neuropathic cancer pain.
AB  - In a randomized, double-blind, crossover study, we evaluated the effect of
      intravenous lidocaine (5 mg/kg body weight over 30 min) on the neuropathic pain
      of advanced cancer patients. Pain intensity, assessed by a visual analogue scale,
      did not show any significant difference between lidocaine and placebo infusion.
      The blinded choice of patients and investigators also suggested no significant
      improvement from lidocaine when given by this regimen. Intravenous lidocaine does
      not appear to have a significant analgesic effect on neuropathic cancer pain.

PMID- 16967581
TI  - Physician attitudes and beliefs about use of morphine for cancer pain.
AB  - The recent literature asserts that mistaken physician beliefs and attitudes are
      critical barriers to adequate cancer pain relief. To determine the prevalence of
      12 proposed myths or misconceptions about morphine use in cancer pain management
      (CPM), we surveyed all physicians engaged in direct patient care in Duluth,
      Minnesota (N = 243). A 62% response was obtained. Many physicians misunderstood
      concepts of morphine tolerance, both to analgesia (51%) and to side effects
      (39%). Many were unaware of the use of adjuvant analgesics (29%), efficacy of
      oral morphine (27%), and nonexistent risk of addiction in CPM (20%). Analysis of
      result by physician age and specialy groups confirmed significant levels of
      misunderstanding in all subsets. Strategies to change physician attitudes and
      beliefs regarding morphine in CPM should focus on tolerance concepts, dosing
      schemes, safety, efficacy, lack of addictive risk, use of drug combinations, and
      the fact that cancer pain can be relieved.

PMID- 16967582
TI  - The role of patient-controlled analgesia in the management of cancer pain.
AB  - The technology of patient-controlled analgesia (PCA) has gained wide acceptance
      for use in cancer pain management. Assessment of technological innovations is
      necessary in order to evaluate the most appropriate use from the perspective of
      the individual patient and broader health policy perspective. This paper reviews
      the literature related to PCA use in chronic cancer pain, appropriate and
      inappropriate uses of PCA, as well as several professional issues and directions
      for future PCA use. Professional dialogue regarding the standard of PCA care is
      necessary for optimum use of this technology for relief of chronic pain.

PMID- 16967583
TI  - Cancer pain control by infusion techniques in the home situation in the Northern
      Netherlands: an innovative project on the use of medical technology in the home
      situation.
AB  - Since 1982, 229 terminally ill cancer pain patients were treated by the
      administration of epidural opioids. An adequate level of aid was provided by the
      coordinated efforts of the patients' general practitioner, the district nurse,
      and the anesthesiologist. Based on 9 yr of experience with this model, a project
      on quality improvement and organization of cancer pain control by infusion
      techniques in the home situation was proposed. The purpose of the study is to
      create a nationwide organization for cancer pain control for terminal patients on
      a home-care basis. Specially trained ambulatory field teams will be set up to
      collect and process the information necessary to make protocols and instructions.

PMID- 16967584
TI  - Novel delivery systems: electrotransport.
AB  - Electrotransport involves the transport of ionized drugs across the skin under
      the influence of an electric current. This method of delivery has been used for
      many years to deliver drugs locally to the skin or the mouth, but now it is being
      studied as a means of delivering drugs for their systemic effects. Opioid
      analgesics may be administered via this route.

PMID- 16967585
TI  - Novel delivery systems: oral transmucosal and intranasal transmucosal.
AB  - During the past 2 decades, anesthesiologists have been provided with a number of
      new, potent opioid analgesics and sedative/hypnotics, as well as an increased
      understanding of the pharmacokinetic and pharmacodynamic principles that govern
      their action and disposition. These developments have suggested that the skin and
      the buccal and nasal mucous membranes may have use as alternate routes of
      analgesic and anesthetic drug delivery. A novel transmucosal delivery system for
      fentanyl has recently been developed by incorporating the drug into a dissolvable
      matrix on a stick called an "oralete." Oral transmucosal fentanyl citrate has
      been evaluated as a premedication in the pediatric population and as an
      analgesicfor acute postoperative and emergency room pain, procedural pain, and
      breakthrough cancer pain by using fentanyl. Increases in plasma fentanyl and
      onset of clinical effect are rapid (20-40 min) with this formulation. A potential
      advantage is the apparent ease of titration to a sedative or analgesic end point.
      This system may improve premedication, acute postoperative analgesia, and chronic
      pain therapy in various clinical settings. Delivery of opioids through the nasal
      mucosa also has been recently investigated. In one study, sufentanil was
      administered (1.5, 3.0, or 4.5 mu/kg) to 80 children ranging in age from 6 mo to
      7yr. Easy separation from parents was achieved in 86% of the children 10 min
      following administration of the premedication. Unfortunately, 61% of the children
      cried after drug administration, and side effects included reduced ventilatory
      compliance (chest-wall rigidity) with higher doses (3.0 and 4.5 microg/kg).
      Nevertheless, nasal transmucosal drug delivery may have value, especially in
      frightened or uncooperative children.

PMID- 16967586
TI  - Response of central pain syndromes to intravenous lidocaine.
AB  - In this study, 8 patients with central pain syndromes, 6 with hemispheric
      lesions, and 2 with spinal cord lesions were treated with a 1 mg/kg dose of
      intravenous lidocaine. Patients first received the same volume of normal saline,
      in single-blind fashion, to monitor placebo effects. Of the 8 patients, 7
      responded to lidocaine, and only 1 responded to normal saline. Responses ranged
      from partial to complete. All components of central pain, including constant
      pain, paroxysms ofpain, and evoked pain, responded to lidocaine. In addition, 3
      patients had pain relief that lasted for 8-20 wk. These findings, which are in
      agreement with two previous open-label studies, suggest that a single dose of a
      local anesthetic, lidocaine, can provide lasting pain relief for patients with
      central pain syndromes. This analgesic action may be central, and possibly
      supraspinal, at least in patients with hemispheric lesions.

PMID- 16967587
TI  - Relief of intractable pain from metastatic multiple myeloma using epidural phenol
      injections.

PMID- 16967588
TI  - [Coma in a child after treatment with the 'magic salve' lidocaine-prilocaine
      cream].
AB  - A 2-year-old girl lost consciousness after the topical application of lidocaine
      prilocaine cream (EMLA) in preparation for the removal of multiple mollusca
      contagiosa. Both the area on which cream was applied (80% of body surface) and
      the total amount of cream (90 g) exceeded the maximum dosage. Lidocaine
      prilocaine cream is a widely used local anaesthetic with few side effects when
      used properly. Intoxication with a lidocaine-prilocaine preparation may have
      serious consequences, such as changes in intracardiac conduction, excitation or
      depression of the central nervous system and methaemoglobinaemia. In our patient
      both methaemoglobinaemia and depression of the central nervous system occurred,
      resulting in loss of consciousness. She was treated with 100% oxygen and fully
      recovered.

PMID- 16967589
TI  - [Legionella outbreak in Amsterdam: a cooling tower as the source].
AB  - During the period 6-28 July 2006, 30 confirmed cases of Legionella infection were
      identified in Amsterdam, 2 of which were fatal. All had a positive urinary
      antigen test, by which Legionella pneumophila serogroup I could be demonstrated.
      Consultations between the parties involved in the control of infectious diseases
      started on July 7th, as soon as it became clear that there was an outbreak. On
      July 10th it was established that relatively many of these patients lived in the
      eastern part of the city centre. After a study of the prevailing winds during the
      past 3 weeks, the search for installations containing water was started. A
      cooling tower in the town centre was closed on July 11th by way of precaution.
      During the following week, this tower was proven to be the source of the
      outbreak.

PMID- 16967590
TI  - [The combination of acetylsalicylic acid and dipyridamole is more effective in
      secondary prevention following transient ischaemic attack or cerebral infarction:
      the debate is closed].
AB  - The European/Australasian stroke prevention in reversible ischaemia trial
      (ESPRIT) confirms that long-term administration of the combination
      acetylsalicylic acid and dipyridamole is more effective than acetylsalicylic acid
      in reducing the risk of vascular events after cerebral ischaemia of arterial
      origin. The results of this study in combination with the results of previous
      studies have provided sufficient evidence for the use of this therapy in clinical
      practice.

PMID- 16967591
TI  - [The risk of yellow fever in travellers].
AB  - Yellow fever is a tropical virus disease characterised by high fever, jaundice,
      heart and kidney failure, and haemorrhagic diathesis. The causative Flavivirus is
      endemic in parts of tropical Africa and South America and is transmitted among
      humans and primates by mosquitoes. The chance that an unvaccinated traveller to
      West Africa will die of yellow fever is estimated at 1:650 to 1:5000 visitors per
      month of stay, depending on whether an epidemic occurs. Vaccination with the
      attenuated yellow fever Asibi 17D virus results in limited virus replication in
      the body and long-term protection due to the formation of neutralising
      antibodies. Vaccination is contraindicated in immunocompromised persons. Serious
      disseminated disease and encephalitis due to infection with the vaccine virus
      strain are seen more often in the elderly. One should therefore refrain from
      vaccination in persons over 60 years of age when the risk of infection is
      negligible. In recent years, the number of yellow fever epidemics has risen
      substantially, particularly in West Africa and the Amazon region. Reintroduction
      of yellow fever vaccination in childhood vaccination programmes is necessary in
      endemic areas to turn the tide of increasing outbreaks of yellow fever.

PMID- 16967592
TI  - [Coffee consumption and the decreased risk of diabetes mellitus type 2].
AB  - Coffee is among the most commonly consumed beverages in The Netherlands. Caffeine
      can acutely lower insulin sensitivity, but it is not clear whether tolerance for
      this effect develops after long-term regular intake. Furthermore, it is plausible
      that the effects of coffee are different from those of caffeine. Coffee contains
      hundreds of substances and there are indications that certain components may
      partly counter-act the effect of caffeine or may have independent beneficial
      effects. Intake of the coffee components chlorogenic acid, quinides, lignans, and
      trigonelline improved glucose metabolism in animal studies. Habitual coffee
      consumption has been studied in relation to the risk of diabetes mellitus type 2
      in 12 cohort studies in Europe, the USA, and Japan. Generally, high coffee
      consumption was associated with a substantially lower risk of type-2 diabetes.
      The findings were similar for caffeinated and decaffeinated coffee, suggesting
      that the non-caffeine components of coffee may be responsible. Identification of
      these coffee components may lead to the development or selection of coffee types
      with improved effects on health.

PMID- 16967593
TI  - [From the Cochrane Library and Diabetes Care: self-monitoring of blood glucose
      probably an effective way to improve glycaemic control in patients with type 2
      diabetes not taking insulin].
AB  - Self-monitoring of blood glucose has been found to be effective for patients with
      type I diabetes and for patients with type 2 diabetes taking insulin. There is
      much debate on the effectiveness of self-monitoring of blood glucose in the
      management of patients with type 2 diabetes who are not taking insulin. A
      systematic review of 6 randomised controlled trials comparing self-monitoring of
      blood glucose with standard care, self-monitoring of urine glucose, or both
      showed that self-monitoring of blood glucose may be effective in improving
      glycaemic control in patients with type 2 diabetes who are not using insulin.
      There was scant data on patient-related outcomes, such as quality of life, well
      being and satisfaction. Therefore, more large long-term studies of high quality
      are needed.

PMID- 16967594
TI  - [Diagnostic image (287). A newborn with exanthema].
AB  - A 4-week-old girl presented with annular skin lesions caused by neonatal lupus
      syndrome.

PMID- 16967596
TI  - [Gynaecomastia and male infertility as symptoms of a nonpalpable Leydig cell
      tumour].
AB  - A 35-year-old man and his partner were referred for intracytoplasmic sperm
      injection treatment (ICSI) because of secondary infertility due to severe
      oligoasthenoteratospermia. Three years earlier he had presented elsewhere with
      left unilateral gynaecomastia. A hypertrophic mammary gland had been excised one
      year later. Histopathological investigation showed benign hypertrophy. One year
      later he developed gynaecomastia on the other side. Physical examination and
      incomplete hormonal screening showed no abnormalities. The couple were referred
      to our tertiary clinic for ICSI treatment. The patient still had unilateral
      gynaecomastia. Hormonal screening showed not only severe
      oligoasthenoteratospermia, but also an elevated serum oestrogen level. Scrotal
      ultrasound revealed a 17 mm mass in his right testicle. Subsequently unilateral
      orchidectomy was performed. Histology showed a benign Leydig cell tumour for
      which no further therapy was required. Four months after surgery the
      gynaecomastia diminished, oestrogen levels became normal and improvement in semen
      parameters followed. Patients with severe male infertility or gynaecomastia are
      at a higher risk of developing a testicular neoplasm. Besides history taking,
      physical examination of breasts and testicles, hormonal screening and scrotal
      sonography should be performed as some testicular neoplasms are not apparent on
      palpation.

PMID- 16967597
TI  - [A nationwide Dutch study into the optimal treatment of patients with infected
      necrotising pancreatitis: the PANTER trial].
AB  - Surgical intervention in infected necrotising pancreatitis generally consists of
      necrosectomy via laparotomy. The morbidity and mortality after this procedure
      might be reduced by minimally invasive strategies. The 20 hospitals of the Dutch
      Acute Pancreatitis Study Group are currently enrolling patients in a randomised
      trial to compare (a) laparotomy with necrosectomy and continuous postoperative
      lavage with (b) CT-guided or endoscopic transgastric drainage, if necessary,
      followed by videoscopic assisted retroperitoneal debridement (VARD): the PANTER
      trial ('pancreatitis, necrosectomy versus a minimally invasive step-up
      approach'). The primary endpoint is the proportion of patients suffering from
      major postoperative morbidity and mortality. Patients with (suspected) infected
      necrotising pancreatitis can be put forward for participation in the trial in one
      of the 20 participating centres.

PMID- 16967598
TI  - [Severe disciplinary measures in the Millecam case: important precedent for
      revising the rules of conduct by scientific associations and the KNMG].
AB  - The popular 45-year-old Dutch actress Sylvia Millecam died in August 2001 from
      untreated advanced breast cancer. She refused standard medical treatment and
      sought solace in many alternative healers, including three medical physicians.
      The Dutch Healthcare Inspection accused the three physicians of malpractice and
      asked the Medical Disciplinary Tribunal to pass judgment. In April 2006 one
      physician was struck from the physician register and the other two were suspended
      for 1 year and 6 months, respectively. These unusually severe measures were based
      mainly on the fact that they had neglected professional standards as defined by
      specialty boards, they had presented themselves as professional physicians and
      they had not tried hard enough to convince Millecam of the need for standard
      treatment. The Tribunal did not accept the strong desire of the patient to
      undergo only alternative treatment as a defence. Notably, the judgment of the
      Tribunal seems to be more severe than the present bylaws of medical-scientific
      bodies and the Dutch Medical Association (KNMG), which are apparently too lenient
      regarding the use of alternative treatments by their members.

PMID- 16967599
TI  - [Medical assistance by doctors on board an aircraft].

PMID- 16967600
TI  - [Medical assistance by doctors on board an aircraft].

PMID- 16967601
TI  - [Nitrous oxide sedation].

PMID- 16967602
TI  - [Remicade: six years of experience in immune-mediated inflammatory disorders].

PMID- 16967603
TI  - [Tolerance of anti-TNF alpha: the experience acquired in inflammatory rheumatic
      disease].

PMID- 16967604
TI  - [Remicade in moderate to severe plaque psoriasis].

PMID- 16967606
TI  - [Treatment of early arthritis--recommendations of EULAR].
AB  - Team of fourteen prominent rheumatologists created the "Recommendations for the
      therapy of early arthritis" based on standard operating procedures. This
      publication was made on the basis of analysis of previously published double
      blind studies (the so-called evidence based procedure) and mutual consensus of
      the authors.

PMID- 16967607
TI  - [Gastroduodenal complications associated with non-steroidal anti-inflammatory
      drugs in Slovak Republic: results of one-year prospective study].
AB  - The aim of the one-year prospective study was to estimate the prevalence of non
      steroidal anti-inflammatory drugs using in patients with symptomatic
      gastroduodenal ulcers, the upper gastrointestinal bleeding and perforation (PUB-
      perforation, ulcer, bleeding). Among of 326 patients with PUB, prevalence of non
      steroidal anti-inflammatory drugs using was 60%. In the group of 194 patients
      with non-steroidal antiinflammatory drugs induced PUB, 49% patients took aspirin,
      38% non-aspirin non-steroidal anti-inflammatory drugs and 13% their combination.
      Low dosing aspirin (daily dosis < or =200 mg) was associated with PUB in 21% of
      patients. Age higher than 60 years and women had statisticaly signiticant higher
      prevalence of non-steroidal anti-inflammatory drugs induced PUB.

PMID- 16967608
TI  - [Problems of cardiovascular toxicity of coxibs and non-selective NSA].
AB  - Non-steroidal antirheumatics (NSA) belong to the most often prescribed drugs.
      Certain observation studies indicate that they are used by 20 to 30% of
      population of developed countries. The most common NSA's adverse effects are
      gastrointestinal complications. Coxibs have been developed as an alternative to
      conventional non-selective NSA; with similar efficacy, they should reduce the
      risk of development of gastrointestinal complications. In the few last years,
      possible toxicity of coxibs and other non-steroidal antirheumatics has been
      widely discussed. The VIGOR study, which was performed 6 years ago, showed five
      times higher incidence of nonfatal myocardial infarction in patients with
      rofecoxib therapy as compared with naproxen. Afterwards, there was much debate
      about rofecoxib, and coxibs in general, whose cardiotoxicity was supported and
      confuted at the same time. Possible cardioprotective effect of naproxen was
      discussed too. Later on, results of the APPROVE study (Adenoma Polyp Prevention
      on Vioxx) made Merck & Co., Inc. withdraw rofecoxib from all markets voluntarily.
      In the end of 2004, three controversial studies on celecoxib were published.
      Although the first study (Adenoma Prevention with Celecoxib study, APC) showed
      higher cardiovascular risk of celecoxib, the second study (Prevention of
      Adenomatosus Polyps, PreSAP) did not verify these results. Surprisingly, the
      third study (Alzheimer Disease and Prevention Trial, ADAPT) proved 50% increase
      of the risk of cardiovascular (CV) toxicity of naproxen. In the last year,
      researchers have tried to decide whether CV toxicity is a class effect of coxib
      group or a class effect of all NSA. Many observation studies proved higher CV
      risk both of coxibs (particularly rofecoxib) and non-selective NSA including
      naproxen. These new findings moved the American FDA (Food and Drug
      Administration) to publish guidance concerning higher CV risk of all coxibs and
      NSA. For the time being, the EMEA (European Agency for Evaluation of Medicinal
      Products) does not change its attitude to NSA; coxibs are contraindicated in
      patients with ischemic heart disease, cerebrovascular disease and peripheral
      artery disease; they should be used with caution in high-risk patients. Final
      assessment of the problems of CV toxicity of NSA and coxibs will be a case of a
      long-term randomized study focused on the incidence of cardiovascular adverse
      effects.

PMID- 16967609
TI  - [Nonsteroidal antiinflammatory drugs and the kidney].
AB  - Nonsteroidal antiinflammatory drugs (NSAIDs) have potentially important renal
      adverse effects. With regard to renal adverse effects there is no indication of
      significant differences between conventional NSAIDs and selective COX-2
      inhibitors. Their nephrotoxicity has been well documented. Many of the renal
      abnormalities that are encountered as a result of NSAIDs use can be attributed to
      the inhibition of prostaglandins synthesis. The release of prostaglandins is
      particulary importent in high-risk patients, including patients with severe heart
      disease, liver disease, preexisting renal disease, elderly and patients with
      volume depletion. The common complication of NSAID use is retention of sodium and
      edema formation due to increased reabsorption of sodium and water in the loop of
      Henle and hyperkalemie due to diminished renin secretion. Nonsteroidal
      antiiflammatory drugs can induce two different forms of acute renal failure.
      Decreased prostaglandin synthesis can lead to reversible renal ischemia and
      hemodynamically-mediated acute renal failure. Second form of acute renal failure
      is acute interstitial nephritis. This type of interstitial nephritis is often
      accompanied by nephrotic syndrome due to minimal change disease. Nephrotic
      syndrome after NSAIDs treatments may be also associated with membranous
      nephropathy. Another complication of NSAIDs treatment is modest rise of systemic
      blood pressure in some hypertensive patients due to increase in renal and
      systemic vascular resistence. In patients consuming excessive amount of NSAIDs
      over a prolonged period of years papillary necrosis can occur. Exposure to large
      quantities of NSAIDs can probably induce in some patients chronic renal
      insufficiency.

PMID- 16967610
TI  - [Polymyalgia rheumatica and giant cell arteritis--first results of a year-long
      study].
AB  - INTRODUCTION: Due to ageing of population, gerontorheumatology becomes more and
      more important. Both polymyalgia rheumatica (PMR) and giant cell arteritis (GCA)
      typically develop in later life and they have many other common features. The aim
      of our study was to explore diagnostic and prognostic markers and, prospectively,
      establish diagnostic and therapeutic algorithm for patients with PMR and GCA.
      SAMPLE AND METHODS: We examined 27 patients with suspected PMR or OBA. The
      diagnosis was verified in 22 patients. Three of them were in a long-term clinical
      remission. Besides examination for basic clinical and laboratory parameters, all
      other patients were subjected to ultrasonography of temporal artery and
      peripheral joints to detect any exudates. Also, they were examined for T-cell
      subpopulations in peripheral blood and HLA antigens. RESULTS: Exudate was
      confirmed in 7 patients; some of them had exudate in multiple joints. Puncture of
      synovial fluid was done in 4 patients. Increased resistance index of temporal
      artery was found in 2 patients with GCA and 4 patients with PMR. GCA patients
      showed lower level of T-cells and increased activation of CD8-cells. Decreased
      count of CD8+ T-cells was observed in 56 % of PMR patients. Analysis of HLA
      antigens indicates that GCA, rheumatoid arthritis and, probably, PMR are
      associated with HLA-DR4 antigen in Slovak population. CONCLUSION: The importance
      of assessment of disease activity and its prognosis in PMR or GCA patients via
      ultrasonographic evaluation of exudate in peripheral joints and resistance index
      of temporal artery as well as the analysis of T-cell distribution in peripheral
      blood and incidence of HLA-antigens has not been proved yet. Practical
      significance of monitoring the above-mentioned parameters can be verified only by
      further prospective study performed with a larger sample of patients.

PMID- 16967611
TI  - [How can the autoantibody detection help in the diagnostics and evaluation of
      autoimmune rheumatic diseases?].
AB  - Autoantibodies are immunoglobulins that are directed against self tissues.
      Variable structural components of the cells or their products may be the targets.
      Production of a majority of autoantibodies is a physiological phenomenon, which
      does not have to lead to the disease. Autoantibodies that are associated with
      connective tissue diseases are produced in high levels, they are usually of high
      affinity and IgG isotype. Connective tissue diseases are characterized by a
      frequent presence of organ non-specific autoantibodies. Some of their properties
      can be used for clinical evaluation. The presence of the autoantibody may
      directly diagnose a specific connective tissue disease or support such a
      diagnosis. Some autoantibodies associate with typical clinical signs and
      symptoms, which sometimes form a specific subgroup with a different prognosis.
      Follow-up of the levels of autoantibodies is less significant, although they may
      occasionally help to assess the activity and contribute to a therapeutic
      decision. It is important to be aware of some technical limits that may affect
      the detection and interpretation of autoantibodies in the laboratory.

PMID- 16967612
TI  - [Systemic lupus erythematodes].
AB  - Systemic lupus erythematodes (SLE) is chronic autoimmune disease, characteristic
      by production of autoantibodies against different autoantigens. Etiopathogenesis
      in not precise determinated, but genetic, immunologic, hormonal factors or
      influence of environment are assumed. It manifests by various symptoms and it can
      affect whichever organ or system in the body. Clinical manifestation are due
      chronic inflammation in the tissues, which is caused first of all by deposit of
      immunocomplex and by cytotoxic damage. At the last decades the mortality of
      patients with SLE is markly lower and their live is prolong. In spite of this
      diagnostic, to follow up and therapy of this disease is complicated and it
      requires the colaboration of more branches of medicine.

PMID- 16967613
TI  - [New trends in diagnosis and treatment of systemic sclerosis].
AB  - Systemic sclerosis (SSc) is a generalised connective tissue disease of unknown
      origin, which clinically shows by skin thickening and sclerosis of different
      extent (scleroderma) and by typical involvement of visceral organs. At the same
      time fibrotic and sclerotic changes occur in the blood vesel walls. SSc usually
      involves females at young and middle age. Myalgias, arthralgias and arthritis are
      nonspecific, tendon friction rubs in fingers are more typical for this diagnosis.
      Gastrointestinal involvement starts early in the oropharyngeal part, esophagus
      and proceeds into the distal parts. Fibrotic changes lead to slow transit
      dysmotility and pseudoobstruction and/or dilation of the bowels. The main
      symptoms are dysphagia, pyrosis, malabsorption and constipation. SSc produces two
      major patterns of abnormality within the lungs a fibrosing alveolitis or a
      primary pulmonary vascular disease. More frequently an insterstitial process
      develops which can be followed by pulmonary arterial hypertension. Cardiac
      involvement can also have different forms. Myocardial fibrosis usually appears at
      first in the conduction system by arrhythmias and various conduction blocks while
      pericarditis is mostly asymptomatic. Renal manifestation of SSc is observed in 8
      10% patients. The most severe form--scleroderma renal crisis is characterised by
      the new onset of accelerated hypertension and rapidly progressive oliguric renal
      failure. No therapies have been proven to modify the course of SSc. Some of the
      drugs can affect only the skin changes. Majority of the currently applied agents
      have only a symptomatic effect.

PMID- 16967614
TI  - [Antiphospholipid syndrome].
AB  - Antiphospholipid syndrome (APS), first described and termed in the early 1980's,
      is defined by its clinical and laboratory signs. If other disorders inducing
      antibody production are excluded, APS may be considered a primary disease. Or it
      can be a secondary condition that is usually seen in systemic diseases of
      connective tissues. The main concept of APS is based on strong association
      between its clinical and laboratory manifestations and patient's medical history.
      Clinical signs include recurrent arterial and venous thrombosis or repeated fetal
      losses; laboratory criteria involve lupus anticoagulant (LA) syndrome or medium
      and high titres of anticardiolipin (aCL) antibodies. Thus defined, APS represents
      the most common form of acquired thrombophilic conditions while the basic concept
      lies in strong association between specific clinical manifestations and repeated
      detection of LA or aCL. Antiphospholipid antibodies (LA and aCL) are extremely
      heterogeneous antibody groups whose effect on processes at different levels of
      coagulation cascade varies. Their effect can be analogical to the action of
      phospholipid surfaces at various points of blood coagulation. This process
      usually results in development of a certain degree of thrombophilia. Present
      level of understanding of APS indicates that characteristics of clinical signs
      and detection and evaluation of antiphospholipid antibodies have not been
      definitely established yet and are to be specified with the help of molecular
      geneticists, immunologists, biochemists, hematologists and rheumatologists.

PMID- 16967615
TI  - [Early diagnosis of ankylosing spondylitis].
AB  - The present study surveys the problems of diagnostics of early ankylosing
      spondylitis (AS) and axial spondylarthritis (SpA). Epidemiologic studies
      repeatedly identified seven- to nine-year delay of diagnosis of AS from its
      development to its first manifestations. Delayed diagnostics is caused both by
      unfamiliarity of rheumatologists with the disease and the inappropriateness of
      New York classification criteria for early stages of AS. In this study, we
      suggest diagnostic algorithms allowing high probability diagnosis of AS/axial in
      X-ray silent stage (the so-called pre X-ray stage). Spondylarthritis represents
      approximately 5% of a total number of chronic low back pain (CLBP) cases. The
      probability grows up to 15% with the presence of inflammatory character of back
      pain. The presence of HLA B 27 increases the probability to 59% and the
      occurrence of other 1 or 2 clinical signs raises the probability up to 90%.
      Probability reaches 95% with positive MRI. The overall concept requires
      verification of new samples in a prospective study. After certification of such
      study, it will be possible to use biological medications for much more efficient
      therapy of patients in early AS stages.

PMID- 16967616
TI  - [Ankylosing spondylitis--the current situation and new therapeutic options].
AB  - Ankylosing spondylitis (AS) is a chronic, immunologically mediated rheumatic
      disease whose progression largely depends on the extent of inflammatory activity.
      In contrast to rheumatoid arthritis (RA), therapeutic control of AS is very
      limited. Therapy of ankylosing spondylitis should not only control inflammatory
      processes, but also prevent structural damages and maintain the functions. Until
      recently, physiotherapy and non-steroidal antiphlogistics (NSA) therapy was a
      gold standard of AS treatment. NSA therapy alleviates inflammatory pain of spine
      in 60 to 80% of patients. According to the most recent findings, long-term
      administration of NSA can affect also X-ray progression. DMARD therapy, which is
      efficient in RA, has insignificant effect on axial form of AS. Sulfasalazine
      proved to be efficacious against peripheral form of AS; administration of MTX and
      leflunomide is not supported by controlled studies. Peripheral arthritis and
      enthesitis is usually treated by short-term application of corticoids. The fact
      remains that an important role in AS immunopathogenesis is played by TNF alpha
      whose increased levels were found in patients with AS in serum, synovial fluid
      and SI joints. Anti-TNF therapy with infliximab and etanercept proved to be
      highly efficacious in patients with AS resistant to conventional therapy.
      Infliximab and etanercept reduced the disease activity (50% improvement in more
      than half of patients), improved the function and slowed down the structural
      damage. MRI studies of anti-TNF therapy proved reduction of inflammatory activity
      in SI joints and spine. Other studies verified the efficacy of adalimumab in AS
      therapy and showed that adalimumab is a promising drug. Also, several randomized
      clinical studies proved efficacy of thalidomide whose administration, however, is
      limited by its severe adverse effects. Until now, the results of studies focused
      on pamidronate therapy appear to be rather controversial. Better understanding of
      AS pathogenesis led to implementation of new therapeutic procedures that
      significantly improve activity and functional condition of patients.

PMID- 16967617
TI  - [Pathogenesis, diagnostics and therapy of gout].
AB  - Gout refers to heterogeneous group of metabolic diseases characterized by
      production of deposits of sodium urate crystals in tissues. Gout manifests as
      acute gouty arthritis with classic clinical picture, or as chronic gouty
      arthropathy with periarticular and subcutaneous deposits of sodium urate
      crystals, i.e. tophi. As for kidney, gout is manifested as acute or chronic gouty
      nephropathy and urolithiasis. These manifestations occur separately or they are
      combined. Hyperuricemia of primary gout is caused rather by impaired renal
      secretion than overproduction of uric acid. Secondary hyperuricemia is associated
      with many pathological conditions; it is also connected with the use of various
      medicaments. Pathogenesis of gouty arthritis is critically influenced by sodium
      urate crystals and inflammatory processes they induce. Hyperuricemia is part of
      metabolic syndrome X which is associated with unanswered question of the
      relationship between uric acid and atherosclerosis. Although gouty arthritis is
      the most frequent inflammatory disease of joints in men over 50 years of age, it
      is often diagnosed and treated inadequately. On that account, the indication of
      long-term hypouricemic therapy should be always based on the following criteria:
      secondary causes of hyperuricemia have to be excluded first; frequency of gout
      attacks and the risk of their recurrence should be taken into consideration; then
      it is necessary to search for renal manifestations of gout; and last but not
      least, we should check whether there are any associated diseases classified in
      metabolic syndrome X.

PMID- 16967618
TI  - [Musculoskeletal manifestations of diabetes mellitus].
AB  - The article outlines changes of locomotor system in patients with diabetes
      mellitus. Classification of individual diseases is based on the requirements of
      clinical practice mainly. The following diseases are described here: diabetic
      cheiroarthropathy, shoulder impingement syndrome, Charcots joint, diffuse
      idiopathic skeletal hyperostosis, diabetic osteopathy and other pathologies
      associated with diabetes.

PMID- 16967620
TI  - The decision to trust.
AB  - Surveys have shown that 80% of Americans don't trust corporate executives and-
      worse--that roughly half of all managers don't trust their own leaders. Mergers,
      downsizing, and globalization have accelerated the pace of change in
      organizations, creating a crisis of trust that didn't exist a generation ago.
      Leaders who understand how trust is built can actively influence its development,
      resulting in a more supportive and productive work environment and, not
      incidentally, a competitive advantage in the war for talent. Building on research
      in social psychology, and on his 15 years of experience consulting on trust, the
      author has developed a model for predicting whether trust or distrust will be
      chosen in a given situation. It helps managers analyze ten factors at play in the
      decision-making process. Hundreds of top executives have used it to diagnose and
      address the root causes of distrust in their work relationships. Some of the
      factors in the model relate to the decision maker: How tolerant of risk, how well
      adjusted, and how relatively powerful is he or she? Others relate to the specific
      situation: How closely aligned are the interests of the parties concerned? Does
      the person who is asking to be trusted demonstrate competence? Predictability and
      integrity? Frequent and honest communication? Sue, a relatively new VP of sales,
      used the trust model to manage her relationship with Joe, an employee nearing
      retirement who was not performing well in a new sales role. Fearing for his job,
      Joe wasn't initially inclined to trust her. Sue took concrete steps to
      communicate openly with Joe, explore other options for him, and show concern for
      his well-being. When joe was transferred, he let his former colleagues know how
      pleased he was with Sue's handling of the situation. As a result, the level of
      trust increased in Sue's department, even though it was experiencing major
      change.

PMID- 16967619
TI  - [Present possibilities of diagnostics and therapy of osteoporosis].
AB  - The occurence of osteoporosis is not so poor in industrial countries, together
      with advance of socioeconomical level and spreading of human life's lenght,
      increases the prevalence of osteoporosis, affect about 5-6% of Europe population
      and also raises the number of the most consequential results--fractures,
      complications, dramatically deteriorating health state and limiting social self
      realization of the pacients. Osteoporosis belongs to metabolic bone diseases with
      highly clarified mechanisms of bone tissue decrease and comprehensive diagnostic
      platform, based on combination of imaging and laboratory methods, enabling early
      disease detection, before occurence of fracture complications. In sequence of
      disorder etiology, the adequate therapy is known with continualy increasing
      effectivity and aplication simplicity for pacient, increasing his compliance.
      Increasing public knowledge and prevention put back not only occurance of
      complications, but also onset of the disease. Neverthless, the osteoporosis is
      still hidden danger with serious economic and social impact.

PMID- 16967621
TI  - 10 ways to create shareholder value.
AB  - Executives have developed tunnel vision in their pursuit of shareholder value,
      focusing on short-term performance at the expense of investing in long-term
      growth. It's time to broaden that perspective and begin shaping business
      strategies in light of the competitive landscape, not the shareholder list. In
      this article, Alfred Rappaport offers ten basic principles to help executives
      create lasting shareholder value. For starters, companies should not manage
      earnings or provide earnings guidance; those that fail to embrace this first
      principle of shareholder value will almost certainly be unable to follow the
      rest. Additionally, leaders should make strategic decisions and acquisitions and
      carry assets that maximize expected value, even if near-term earnings are
      negatively affected as a result. During times when there are no credible value
      creating opportunities to invest in the business, companies should avoid using
      excess cash to make investments that look good on the surface but might end up
      destroying value, such as ill-advised, overpriced acquisitions. It would be
      better to return the cash to shareholders in the form of dividends and buybacks.
      Rappaport also offers guidelines for establishing effective pay incentives at
      every level of management; emphasizes that senior executives need to lay their
      wealth on the line just as shareholders do; and urges companies to embrace full
      disclosure, an antidote to short-term earnings obsession that serves to lessen
      investor uncertainty, which could reduce the cost of capital and increase the
      share price. The author notes that a few types of companies--high-tech start-ups,
      for example, and severely capital-constrained organizations--cannot afford to
      ignore market pressures for short-term performance. Most companies with a sound,
      well-executed business model, however, could better realize their potential for
      creating shareholder value by adopting the ten principles.

PMID- 16967622
TI  - Rethinking political correctness.
AB  - Legal and cultural changes over the past 40 years ushered unprecedented numbers
      of women and people of color into companies' professional ranks. Laws now protect
      these traditionally underrepresented groups from blatant forms of discrimination
      in hiring and promotion. Meanwhile, political correctness has reset the standards
      for civility and respect in people's day-to-day interactions. Despite this
      obvious progress, the authors' research has shown that political correctness is a
      double-edged sword. While it has helped many employees feel unlimited by their
      race, gender, or religion,the PC rule book can hinder people's ability to develop
      effective relationships across race, gender, and religious lines. Companies need
      to equip workers with skills--not rules--for building these relationships. The
      authors offer the following five principles for healthy resolution of the
      tensions that commonly arise over difference: Pause to short-circuit the emotion
      and reflect; connect with others, affirming the importance of relationships;
      question yourself to identify blind spots and discover what makes you defensive;
      get genuine support that helps you gain a broader perspective; and shift your
      mind-set from one that says, "You need to change," to one that asks, "What can I
      change?" When people treat their cultural differences--and related conflicts and
      tensions--as opportunities to gain a more accurate view of themselves, one
      another, and the situation, trust builds and relationships become stronger.
      Leaders should put aside the PC rule book and instead model and encourage risk
      taking in the service of building the organization's relational capacity. The
      benefits will reverberate through every dimension of the company's work.

PMID- 16967623
TI  - With friends like these: the art of managing complementors.
AB  - Intel and Microsoft neither buy from nor sell to each other directly, but they
      are undeniably in business together. They are probably the world's most widely
      known pair of complementors--companies that independently provide complementary
      products or services to mutual customers. Complementors increase the value of
      each other's offerings and the size of the total market. So it's not surprising
      that so many just assume that their interests are aligned. Nothing could be
      further from the truth. Discord can develop in many areas, such as pricing,
      technology, standards, and control of the market--both in terms of which company
      has the most influence over customers and which one gets the biggest slice of the
      pie. The issue of pricing perfectly captures this tension. Ideally, you'd like to
      price your goods high while your complementors price theirs low. Airlines, for
      instance, would be happy to see vacation lodgings go for a song, while
      destination resorts could raise rates and still fill their rooms if customers
      could fly there for free. The first step in managing relationships with
      complementors is to develop a deep understanding of their economics, their
      strategies and goals, their existing capabilities, their incentives for
      cooperation, and any potential areas of conflict. Then, to gain the upper hand,
      companies can use a variety of tools that fall into two main categories: hard
      power (inducements or coercion to get what you want) and soft power (persuasion
      through indirect means to get others to want what you want). The authors explain
      how to build both hard power and soft, illustrate the strengths and limits of
      each, and offer guidelines for choosing one over the other. Conflict among
      complementors is inevitable, but together, hard and soft power can help companies
      manage the dark side of complementor relationships and take full advantage of the
      opportunities that cooperation should create.

PMID- 16967624
TI  - How to keep A players productive.
AB  - After graduating from Harvard Business School with highest honors, Jane rapidly
      moved up the corporate ladder at a large advertising firm, racking up promotions
      and responsibilities along the way. By the time she became the company's creative
      director, she was, in everyone's estimation, an A player--one of the
      organization's most gifted and productive employees. But although she received an
      extraordinarily generous pay package and had what some people considered to be
      one of the most stimulating jobs in the company, Jane felt underappreciated and
      was talking to head-hunters. Eventually, she was lured away to a competing
      company that, by her own admission, offered less-challenging work. Both Jane and
      the advertising firm she left behind lost out. Of course, not all A players are
      as vulnerable as Jane. Some superstars soar to stunning heights, needing little
      or no special attention, and have the natural self-confidence and brilliance to
      stay at the top of their game with elegance and grace. But as every manager
      knows, megastars with manageable egos are rare. Far more common are people like
      Jane who are striving to satisfy an inner need for recognition that is often a
      sign of irrationally low self-esteem. According to the author--an executive
      coach, management consultant, and former faculty member of the department of
      psychiatry at Harvard Medical School--if you do not carefully manage the often
      unconscious need A players have for kudos and appreciation, they will burn out in
      a way that is damaging to them and unproductive for you. The key is understanding
      what makes your A players tick. The author suggests that you assist your stars by
      offering them authentic praise, helping them set boundaries, and teaching them to
      play nicely with subordinates. In the process, you can turn these high performers
      into even more effective players.

PMID- 16967625
TI  - Curveball strategies to fool the competition.
AB  - In this follow-on piece to his article "Hardball: Five Killer Strategies for
      Trouncing the Competition" (HBR April 2004), George Stalk of the Boston
      Consulting Group offers another approach for prevailing over rivals. Strategic
      hardball is about playing rough and tough with competitors; strategic curveball
      is about outfoxing them. It involves getting rivals to do something dumb that
      they otherwise wouldn't (that is, swing at a pitch that appears to be in the
      strike zone but isn't) or not do something smart that they otherwise would (that
      is, fail to swing at a pitch that's in the strike zone but appears not to be).
      Stalk describes four types of curveball: Draw your rival out of the profit zone.
      Lure competitors into disadvantageous areas--for example, by competing for, but
      intentionally failing to win, the business of less profitable customers. Borrow
      techniques from unexpected places. Using the hardball tactic of plagiarizing good
      ideas, put rivals off balance by importing techniques from other industries--for
      example, employing the retailer's hard sell in the stodgy world of retail
      financial services. Disguise how you attain your success. Veil your methods by
      achieving an advantage through unlikely means--for example, generating product
      sales through your service operations. Let rivals misinterpret the reasons for
      your success. Allow them to act on conventional but incomplete explanations for
      your success--for example, squeezing costs rather than aggressively utilizing
      assets. The author provides extended examples of these curveball strategies in
      action, at companies such as the industrial-cleaning chemical supplier Ecolab and
      the Australian airline Jetstar.

PMID- 16967626
TI  - The new science of sales force productivity.
AB  - For years, sales managers at many companies have relied on top performers and
      sheer numbers of sales reps to stay competitive. But while they may have squeaked
      by on this wing-and-a-prayer technique, their sales teams haven't thrived the way
      they once did. Today's most successful sales leaders are taking a more scientific
      approach. Savvy managers are reshaping their tactics in response to changing
      markets. They are reaching out to new customers in innovative ways. And they are
      increasing productivity by helping the reps they already have make the most of
      their skills and resources. Leaders who take a scientific approach to sales force
      effectiveness have learned to use four levers to boost their reps' productivity
      in a predictable and manageable way. First, they systematically target their
      firms' offerings, matching the right products with the right customers. Second,
      they optimize the automation, tools, and procedures at their disposal, providing
      reps with the support they need to boost sales.Third, they analyze and manage
      their reps' performance, measuring both internal processes and results to
      determine where their teams' strengths and weaknesses are. Fourth, they pay close
      attention to sales force deployment--how well sales, support, marketing, and
      delivery resources are matched to customers. These four levers can help sales
      leaders increase productivity across the board, the authors say, though they have
      the greatest impact on lower-ranked performers. The overall effect of increasing
      the average sales per employee can be exponential; it means a company won't have
      to rely on just a few talented individuals to stay competitive. This is
      especially important because finding and keeping star salespeople is more
      difficult than ever. What's more, managers who optimize the sales forces they
      already have can see returns they never thought possible.

PMID- 16967627
TI  - When your contract manufacturer becomes your competitor.
AB  - PC maker Lenovo started out as a distributor of equipment made by IBM and other
      companies; now it has formed a joint venture with IBM and will eventually affix
      its own logo to its computers. Shanghai Automotive Industry Corporation (SAIC)
      started out manufacturing vehicles for Volkswagen and GM; now it's preparing to
      sell its own cars in China, Europe, and North America. Lenovo and SAIC represent
      a host of formerly anonymous makers of brand-name products that are breaking out
      of their defined roles and pushing the brands themselves aside. In this article,
      the authors explore the double-edged relationships original equipment
      manufacturers (OEMs) forge with their contract manufacturers (CMs). On the one
      hand, an OEM can reduce its labor costs, free up capital, and improve worker
      productivity by outsourcing all the manufacturing of a product. The company can
      then concentrate on value-adding activities--research and development, product
      design, and marketing, for instance. On the other hand, an OEM that retains a
      contract manufacturer may find itself immersed in a melodrama replete with
      promiscuity (the ambitious CM pursues liaisons with other OEMs), infidelity (the
      OEM's retailers and distributors shift their business to the upstart CM), and
      betrayal (the brazen CM transmits the OEM's intellectual property to the OEM's
      rivals or keeps it for itself when the contract is up). OEMs cannot simply
      terminate their outsourcing arrangements--they need contract manufacturers in
      order to keep specializing, adding value, and staying competitive. But OEMs can
      manage these relationships so that they don't become weak or the CMs too strong.
      Doing so requires modesty about revealing trade secrets; caution about whom one
      consorts with; and a judicious degree of intimacy, loyalty, and generosity toward
      partners and customers.

PMID- 16967628
TI  - The Philadelphia Episiotomy Intervention Study.
AB  - OBJECTIVE: To lower the episiotomy rate through physician education and
      documentation of indication when episiotomy was performed. STUDY DESIGN: The
      intervention consisted of an evidence-based lecture recommending limited usage of
      episiotomy and requesting documentation of any episiotomy's indication. Data 3
      months prior to the intervention were compared to those of the year following.
      Adjusted comparisons of episiotomy rates were completed using multivariate
      logistic regression models. RESULTS: For all vaginal deliveries, there was a 17%
      decrease in the rate of episiotomy, from 46.9% to 38.8%. For spontaneous vaginal
      deliveries, there was a 25% decrease in the episiotomy rate, from 40.8% to 30.8%.
      The most common indications for episiotomy reported were routine/elective, 41.0%;
      vacuum, 18.6%; forceps, 16.4%; and nonreassuring fetal heart tracing, 10.9%.
      CONCLUSION: Episiotomy rates may be effectively reduced through physician
      education and documentation of procedure indication.

PMID- 16967629
TI  - Effects of E2 and E2/norgestimate hormone therapy on elevated baseline lipids.
AB  - OBJECTIVE: To evaluate lipid effects of estradiol/ norgestimate hormone therapy
      in postmenopausal women with elevated lipid levels. STUDY DESIGN: Postmenopausal
      women were randomized to E2, 1 mg/intermittent norgestimate (NGM) 90 microg (n =
      31), or opposed E2, 1 mg (n = 36), in a 12-month trial. A subset analysis was
      conducted on participants with unfavorable baseline lipid levels, either total
      cholesterol (TC) levels > 200 mg/dL, high-density lipoprotein cholesterol (HDL-C)
      levels < 40 mg/dL, low-density lipoprotein cholesterol (LDL-C) levels > or = 160
      mg/dL or triglyceride levels > or = 150 mg/dL. Mean changes and categorical
      shifts were assessed on fasting blood samples collected at baseline and at 7 and
      12 months. RESULTS: Twelve-month mean changes from baseline in women treated with
      E2/NGM included a 19.8% increase in HDL-C and decreases of 13.4% in LDL-C, 17.5%
      in triglycerides and 3.3% in TC. Women with poorer lipid profiles at baseline
      showed the greatest benefit. Results were similar in women randomized to
      unopposed E2. CONCLUSION: E2/NGM and unopposed E2 were similarly beneficial in
      modifying lipid fractions in women with unfavorable baseline levels.

PMID- 16967630
TI  - Concordance of gross surgical and final fixed margins in vulvar intraepithelial
      neoplasia 3 and vulvar cancer.
AB  - OBJECTIVE: To prospectively evaluate the concordance of initial surgical vulvar
      margins and final fixed margins and to determine the amount of microscopic
      pathology of grossly negative margins in women with vulvar intraepithelial
      neoplasia (VIN) 3 or vulvar carcinoma. STUDY DESIGN: Women with VIN 3 or vulvar
      carcinoma undergoing surgical excision were identified. Prior to excision, acetic
      acid was used to highlight the lesions, and 2 sutures were placed, 1 at the edge
      of gross disease and another 1 cm distal from the first. After specimen removal
      and fixation, the distance between sutures and microscopic involvement of VIN was
      determined. RESULTS: Twenty-seven women were enrolled; however, only 19 had final
      fixed specimens that could be accurately measured. The median fixed distance of
      the vulvar margin was 0.85 cm (mean, 0.83; SD, 0.19) as compared to the gross, 1
      cm margin (p = 0.001). Three subjects (16%) had microscopic involvement by VIN 3
      in the grossly negative epithelium between the 2 sutures, but none had a positive
      peripheral margin. CONCLUSION: The gross surgical margin after vulvar resection
      is reduced by 15% when measured in its final fixed state, and a grossly negative
      1-cm margin will seldom harbor significant disease.

PMID- 16967631
TI  - Prediction of ABOG written examination performance from the third-year CREOG in
      training examination results.
AB  - OBJECTIVE: To study the ability of the Council on Resident Education in
      Obstetrics and Gynecology (CREOG) in-training examination score to predict
      American Board of Obstetrics and Gynecology (ABOG) written examination
      performance. STUDY DESIGN: Twenty-six physicians took the CREOG examination
      during the third year of their residency and the ABOG written examination during
      their fourth year. These 2 test scores were compared. RESULTS: There was a
      statistically significant correlation between the 2 examination scores (r = 0.69,
      p < 0.001). CONCLUSION: The CREOG in-training examination at the third year of
      the residency correlates well with the ABOG written examination score and can be
      used to identify residents who need remedial study before finishing the program.

PMID- 16967632
TI  - Hyperemesis gravidarum and nonspecific abnormal EEG findings: a preliminary
      report.
AB  - OBJECTIVE: To evaluate central nervous system abnormalities in a group of
      otherwise healthy pregnant women with hyperemesis gravidarum (HG) during the
      first trimester. STUDY DESIGN: In a case-control study, 17 pregnant women with HG
      during the first trimester (study group) were compared with 18 pregnant women
      without nausea and vomiting in pregnancy (NVP). The latter group included women
      who were planning first-trimester termination of pregnancy for reasons other than
      health (control group). All the pregnant women enrolled in the study answered a
      questionnaire and underwent a physical examination, blood tests, urinalysis, EEG,
      and visual evoked potential (VEP) and brainstem auditory evoked response (BAER)
      tests. RESULTS: An abnormal EEG was found in 5 of the 17 women in the study group
      (29.4%), whereas none of the 18 women in the control group had an abnormal EEG (p
      = 0.013). The VEP and BAER tests were normal among the women in both groups.
      There were no clinically significant differences between the 2 groups with regard
      to maternal age, gravidity, parity, weeks of gestational age, blood count, renal
      function, liver function or electrolytes. Low thyroid stimulating hormone levels
      were found in 6 of the 17 women in the study group (35.3%) as compared to 1 of
      the 18 in the control group (5.5%) (p = 0.028). None of the women in either group
      had hyperthyroidism. HG in previous pregnancies was a significant risk factor for
      HG in the present pregnancy. CONCLUSION: In pregnant women with HG during the
      first trimester, the frequency of abnormal EEG findings is significantly higher
      as compared to that in pregnant women without NVP. However, the mechanism and
      implications of these findings are yet to be clarified.

PMID- 16967633
TI  - Globozoospermia: Do Y-chromosome microdeletions play a role in this rare
      spermatogenic disorder?
AB  - OBJECTIVE: To explore the possible relationship between Y-chromosome
      microdeletions and a rare spermatogenic disorder, globozoospermia. STUDY DESIGN:
      Twelve patients with 100% globozoospermia were evaluated. Each man was questioned
      about his medical and surgical history and underwent a thorough andrologic
      examination. Plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH),
      testosterone and prolactin levels were measured. Routine sperm analysis and
      morphology with electron microscopy were done. A set of 17 Y-specific sequence
      tagged sites spanning the 3 AZF regions and also RBM1, ZFY, SRY, sY78, CDY, BPY2
      and PRY were tested to detect the existence of Y-chromosome microdeletions by
      polymerase chain reaction. RESULTS: The mean age of the patients was 36 years
      (range, 27-42). No patient had abnormal blood concentrations of FSH, LH,
      testosterone or prolactin. Semen analysis revealed normal values for volume (2.2
      mL) and concentration (32 x 10(6)/mL) but subnormal values for motility (37%) and
      progressive motility (24%). On light and electron microscopy, all the spermatozoa
      were round headed, with abnormal morphologic features. Patients had normal 46,XY
      karyotyping. No microdeletion of the Y chromosome was detected in any patient.
      CONCLUSION: Although this study did not find any Y-chromosome microdeletions in
      patients with globozoospermia, the exact genetic locus resulting in this
      pathology requires further study.

PMID- 16967634
TI  - Subjective and objective outcomes of botulinum toxin type A treatment in
      vestibulodynia: pilot data.
AB  - OBJECTIVE: To collect pilot data on the efficacy of intramuscular botulinum toxin
      type A (BTX/A) injection into the levator ani muscles to relieve coital pain,
      reduce pelvic floor tension and instability, and reduce vestibular hyperalgesia
      in vestibulodynia. STUDY DESIGN: Two subjects meeting diagnostic criteria for
      vestibulodynia were treated with 20 units and 40 units of BTX/A at 12-week
      intervals. Outcomes included a visual analogue scale (VAS), weekly coital pain
      diaries, surface electromyography (sEMG) and a vulvar algesiometer. RESULTS:
      BTX/A modestly reduced coital pain in 1 patient and was ineffective in the other.
      Pelvic floor hypertonicity and variability were markedly reduced in both
      patients, but negligible changes occurred in vestibular hyperalgesia. The patient
      with greater pelvic floor tension had more of a reduction in diary-rated coital
      pain 2 weeks after the injection (29% vs. 9%) and on the VAS at 12 weeks (15% vs.
      3%). CONCLUSION: BTX/A injections may be effective in reducing coital pain in
      vestibulodynia with levator ani tenderness but have little effect on vestibular
      allodynia. The relationship between pelvic floor hypertonicity and decreased
      coital pain suggests that vestibulodynia may be a variant of chronic regional
      pain syndrome. The dose and volume of BTX/A injected may be related to the degree
      of relief.

PMID- 16967635
TI  - Patients' knowledge of umbilical cord blood banking.
AB  - OBJECTIVE: To determine patients' knowledge of umbilical cord blood banking
      (UCBB). METHODS: A questionnaire was administered. Part 1 queried issues of
      familiarity with the term UCBB. Those patients with any awareness of UCBB were
      provided with part 2, asking more detailed questions that assessed knowledge.
      RESULTS: Four hundred twenty-five patients completed the survey; 37% had no
      knowledge of UCBB. Older patients and those with higher degrees of education were
      more aware of UCBB, and the greatest disparity of knowledge was noted among
      Native American patients (p < 0.001). Of patients indicating familiarity with
      UCBB, 2.6% felt "extremely knowledgeable," while 74% felt "minimally informed."
      Fifty percent of the patients were misinformed that UCBB was only for "the child
      that I will deliver." Seventy-one percent of patients were not planning UCBB,
      with "expense" and "insufficient knowledge" as the primary reasons cited. Only
      14% of patients were educated about UCBB by their nurse or obstetrician, although
      90% of patients expected their obstetrician to answer their questions on UCBB.
      CONCLUSIONS: Patients are poorly informed about UCBB, especially ethnic
      minorities, younger patients and those with lesser degrees of education. Few
      patients receive UCBB education from health care providers, yet most patients
      expect their obstetrician to be able to answer questions on UCBB. Lack of
      knowledge and expense remain barriers to UCBB. Opportunities to educate patients
      and obstetric providers on UCBB should be pursued.

PMID- 16967636
TI  - Pregnancy outcomes in women with mechanical heart valves.
AB  - OBJECTIVE: To evaluate maternal complications and perinatal outcomes in women
      with mechanical heart valves treated with warfarin and heparin during pregnancy.
      STUDY DESIGN: A retrospective chart review was performed on 45 pregnancies in 28
      women who were previously fitted with mechanical valve prostheses and treated
      between 1991 and 2005 at Seoul National University Hospital. Outcome parameters
      were maternal complications and perinatal outcomes. RESULTS: Overall, there were
      27 live births (60%), 7 stillbirths (15.6%), 2 therapeutic terminations in the
      second trimester (4.4%), 9 first-trimester spontaneous abortions (20%) and 2
      neonatal deaths after preterm delivery. After excluding 9 first-trimester
      spontaneous abortions and 3 pregnancies administered warfarin throughout
      pregnancy, there were significantly more live births among patients administered
      heparin only after a diagnosis of pregnancy than among those administered
      warfarin from the second trimester (11 of 11 vs. 13 of 22, p = 0.015). One
      patient with mitral valve thrombosis during heparinization in the first trimester
      received valve replacement surgery and then aborted. Late postpartum hemorrhage
      occurred in 1 patient. All stillbirths and therapeutic terminations occurred in
      women being administered warfarin. CONCLUSION: Warfarin use from the second
      trimester in combination anticoagulation regimens increases the risk of an
      adverse perinatal outcome.

PMID- 16967637
TI  - Anaphylaxis to cefazolin during labor secondary to prophylaxis for group B
      Streptococcus: a case report.
AB  - BACKGROUND: Anaphylaxis is an uncommon event during pregnancy, but if it does
      arise, it can lead to serious fetal consequences even if there are no serious
      long-term maternal complications. CASE: A parturient developed anaphylaxis in the
      labor unit shortly after intravenous cefazolin chemoprophylaxis had begun for
      perinatal group B streptococcal disease. Prompt treatment for anaphylaxis
      commenced, involving the administration of epinephrine and glucocorticoids, and
      an emergency cesarean section spared the mother serious morbidity, with a
      favorable perinatal outcome for the fetus. CONCLUSION: To the best of our
      knowledge, this case is the first reported one of anaphylaxis to cefazolin in
      pregnancy secondary to prophylaxis against for B Streptococcus. The case
      demonstrates that a life-threatening anaphylactic reaction can occur at any time
      during pregnancy and that all staff in a maternal unit should be familiar with
      the management of perinatal anaphylaxis.

PMID- 16967638
TI  - Natural history of an untreated presumed hydatidiform mole: a case report.
AB  - BACKGROUND: Hydatidiform moles (HMs) usually are evacuated by dilation and
      curettage soon after diagnosis. A small percentage of HMs later progress to
      choriocarcinomas. CASE: A 20-year-old woman presented with signs and symptoms of
      an HM. Through poor medical care, noncompliance and misunderstanding, she delayed
      dilation and curettage for 3 months, until after the condition regressed
      spontaneously. CONCLUSION: HMs masquerading as miscarriages (or other pregnancy
      outcomes) may account for some rogue choriocarcinomas that do not appear to
      follow HMs.

PMID- 16967639
TI  - Placenta percreta diagnosed after first-trimester pregnancy termination: a case
      report.
AB  - BACKGROUND: Placenta percreta in early pregnancy has been documented in only a
      few cases. This is the first report of placenta percreta diagnosed after an
      extended period from pregnancy termination. CASE: A woman with a history of a
      previous cesarean section presented with heavy and irregular vaginal bleeding
      beginning immediately after pregnancy termination at 7 weeks' gestation. Failed
      response to hormonal treatment and curettage necessitated hysterectomy.
      Histologic examination revealed a placenta percreta. CONCLUSION: Although
      placenta percreta is an uncommon occurrence, clinicians should consider it in
      patients who have a uterotomy scar and complain of long-term metrorrhagia
      following pregnancy termination.

PMID- 16967640
TI  - Group A streptococcal toxic shock syndrome after an office endometrial biopsy: a
      case report.
AB  - BACKGROUND: Endometrial biopsy is a common office procedure and is relatively
      free of serious complications. CASE: A 43-year-old woman presented with fevers,
      vaginal bleeding and abdominal pain after an office endometrial biopsy. She was
      found to have sepsis, shock abdominal tenderness and an erythematous rash. She
      was managed with intravenous antibiotics and fluid resuscitation. Once stable,
      she underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy,
      with findings of acute pelvic infection. Blood cultures grew group A beta
      hemolytic Streptococcus. CONCLUSION: Since the 1980s, an increase in severe
      infections caused by Streptococcus pyogenes led to the definition of group A
      streptococcal toxic shock syndrome. This appears to be the first report of
      streptococcal toxic shock syndrome occurring after an endometrial biopsy.

PMID- 16967641
TI  - [Coping and quality of life among children and adolescents with attention
      deficit/hyperactivity disorder].
AB  - First studies suggest an impaired emotion regulation especially with negative
      emotions among children and adolescents with attention deficit/hyperactivity
      disorder (ADHD), which particularly emerged in the subgroup with comorbid conduct
      disorder. Moreover, first results have shown that quality of life of children and
      adolescents with ADHD are negatively affected compared to healthy controls. The
      present study examined differences in age and subgroup on coping and quality of
      life among boys with ADHD. Furthermore, coping and quality of life were compared
      to healthy norms. In total, N=48 boys with ADHD with and without conduct disorder
      (ages 8 to 12 years) were asked to complete self-report questionnaires on coping
      and quality of life. Fifth and sixth graders with ADHD reported less distraction
      than third and fourth graders. The subgroup with ADHD and conduct disorder showed
      more passive avoidance and resignation compared to the subgroup with ADHD alone.
      Compared to normative data, especially third and fourth graders with ADHD showed
      an increased maladaptive coping. Additionally, the subgroup with conduct disorder
      scored higher on all maladaptive coping strategies than the normative sample.
      Finally, all domains of quality of life were impaired among children and
      adolescents with ADHD compared to normative data. These findings support the
      consideration of emotion regulation and quality of life in the research of ADHD
      in childhood and adolescence to develop effective programs for prevention and
      intervention.

PMID- 16967642
TI  - [Life situation and health status of children and adolescents].
AB  - In the last decades an increasing number of characteristics of the child's life
      circumstances have been identified as risk factors for mental health problems. Up
      to now, the natural distribution of these factors in the population has not been
      systematically investigated. In the Hamburg Health Survey N=1950 children and
      adolescents between 4 and 18 years of age and their families representative for
      Germany have been examined. The questionnaire used asks for sociodemographic
      variables, pregnancy and birth, kindergarten and school attendance, psychosocial
      burden and utilization of health services. Complications in pregnancy, birth or
      in the first year of life arise in every fifth child. Severe childhood illnesses,
      serious accidents, hospital stays for longer than 14 days or early changes of
      caregivers have 14% of those investigated. Every tenth child has problems in the
      kindergarten (mostly separation anxiety), every fourth child has problems in
      school (especially problems in concentration or performance) and 8% suffer from
      stressful life events (mostly changed family relations). Mental or physical
      illness and disabilities are found in 8.5% of all families. Although the majority
      of all children and adolescents live in healthy life circumstances, risk factors
      are not as rare as to be neglected. Especially the frequency of problems in
      kindergarten and school as well as stressful life events indicate that preventive
      interventions are necessary.

PMID- 16967643
TI  - [Evaluation of the Faustlos-Curriculum for Kindergartens].
AB  - In this control group study the Faustlos-Kindergarten version was evaluated. This
      violence prevention program is based on strengthening social-emotional
      competences in children. The results of the pre-post-study in 7 intervention and
      7 control kindergartens (N=124 children aged 4; 5-6 years) show significant
      improvements in the childrens' social-emotional competences and significant
      reduction of aggressive behavior in the Faustlos groups in contrast to the
      controls.

PMID- 16967644
TI  - [Autistic spectrum disorders in very young children: issues in the diagnostic
      process].
AB  - The diagnosis of very young children with autistic spectrum disorders and
      differentiating the disorder from mental retardation are difficult in the early
      years. Some efforts to improve diagnostic practice are reviewed. The usefulness
      of standardized behavioural rating scales, observation of core deficits in
      communication and play and parental reports are discussed in view of the author's
      experience with 13 children (2-4 years of age). Even in the case of diagnostic
      uncertainty, focussing early intervention on core symptoms of autism and
      supporting responsive parent-child interactions is recommended in order to
      prevent further social isolation of children with autistic features.

PMID- 16967646
TI  - Make the most of publicly reported quality data.

PMID- 16967645
TI  - JCAHO's new credentialing, privileging standards require provider-specific data.

PMID- 16967647
TI  - Patient satisfaction planner. More care not necessarily better care, study says.

PMID- 16967648
TI  - Patient satisfaction planner. Diabetes care program addresses specific needs.

PMID- 16967649
TI  - Achieve near-100% hand hygiene compliance.

PMID- 16967650
TI  - Ways to avert potential patient care disasters.

PMID- 16967651
TI  - Medication safety gets a close look during survey.

PMID- 16967652
TI  - Thanks for the bad news.

PMID- 16967653
TI  - A craving for sugar hastens slavery in the West.

PMID- 16967654
TI  - Thirty years of academic family medicine in Rhode Island: looking back, looking
      forward.

PMID- 16967655
TI  - Family medicine residency education: staying on the cutting edge.

PMID- 16967656
TI  - Brown Medical School Family Medicine at thirty: residents' views of now and then.

PMID- 16967657
TI  - Fellowship training in family medicine at Brown: adding depth to breadth.
AB  - The Brown Family Medicine fellowship programs share a common goal of nurturing
      the future leaders of our specialty. In a complex and demanding practice
      environment our fellowships have contributed to the development and propagation
      of an adept Family Medicine specialist. These fellowships endorse our specialty's
      broad approach to healthcare through addressing primary care and prevention, but
      also enhance the future of our field through melding the breadth of our
      discipline with the depth of expertise and the stewardship of responsible
      leadership.

PMID- 16967658
TI  - History of the predoctoral division in the department of family medicine at Brown
      Medical School.

PMID- 16967659
TI  - Building a successful research enterprise in family medicine: the Brown
      experience.

PMID- 16967660
TI  - Becoming a doctor.

PMID- 16967661
TI  - Improving health care access for uninsured Rhode Islanders.

PMID- 16967662
TI  - Evidence of increased prostate cancer screening in Rhode Island.

PMID- 16967663
TI  - Skin-deep in words.

PMID- 16967664
TI  - 401(k) plan asset allocation, account balances, and loan activity in 2005.

PMID- 16967665
TI  - Changing face of health care: consumers want centralized care coordination.

PMID- 16967666
TI  - Forward-looking docs go online with benes--and want insurers to pay for it.

PMID- 16967667
TI  - An obligation unmet?

PMID- 16967668
TI  - Resist the 'quick-fix mentality'.

PMID- 16967669
TI  - Looks, ease driving use of mini-implants.

PMID- 16967670
TI  - Persistent orodental pain, atypical odontalgia, and phantom tooth pain: when are
      they neuropathic disorders?
AB  - Patients with unrelenting pain in the teeth, gingival, palatal or alveolar
      tissues often see multiple dentists and have multiple irreversible procedures
      performed and still have their pain. Up to one-third of patients attending a
      chronic facial pain clinic have undergone prior irreversible dental procedures
      for their pain without success. In these cases, if no local source of infectious,
      inflammatory, or other pathology can be found, then the differential diagnosis
      must include a focal neuropathic pain disorder. The common diagnoses given
      include the terms atypical odontalgia, persistent orodental pain, or if teeth
      have been extracted, phantom tooth pain. One possibility is that these pain
      complaints are due to a neuropathic alteration of the trigeminal nerve. There are
      several diagnostic procedures that need to be performed in any patient suspected
      of having a trigeminal neuropathic disorder including (1) cold testing of
      involved teeth for pulpal nonvitality; (2) a periapical radiograph examining the
      teeth for apical change; (3) a panoramic radiograph examining for other
      maxillofacial disease; (4) a thorough head and neck examination also looking for
      abnormality; (5) a cranial nerve examination including anesthetic testing which
      documents any increased or decreased nerve trigeminal nerve sensitivity and rules
      out other neurologic changes outside the trigeminal nerve; and (6) MRI imaging in
      some cases. Finally, when a nonobvious atypical toothache first presents, direct
      microscopic examination of the tooth for incomplete tooth fracture is also
      suggested. The majority of these patients are women over the age 30 with pain in
      the posterior teeth/alveolar arch. Multiple causes exist for sustained
      neuropathic pain including direct nerve injury (e.g., associated with fracture or
      surgical treatment), nerve injection injury, nerve compression injury (e.g.,
      implant, osseous growth, neoplastic invasion) and infection-inflammation damage
      to the nerve itself. Sustained nerve pain is commonly seen in patients with
      psychiatric impairment. It may be that the unrelenting nature of the pain itself
      alters the patient's personality. Treatment includes pharmacologic medications
      which suppress nerve activity. The common medications used for atypical
      odontalgia and phantom tooth pain include gabapentin, tricyclics, topical
      anesthetics, and opioids. A list of these medications is provided in table form.
      Data suggest that once the patient has failed dental treatment and pain persists,
      the long-term outcome is less than 25 percent will have complete pain relief with
      treatment. With earlier treatment, better pain control, and improved nerve
      activity suppression medications, this should also prevent secondary psychiatric
      disease from developing and lower the number of inappropriate treatments.

PMID- 16967671
TI  - Burning mouth syndrome: an update on diagnosis and treatment methods.
AB  - Burning mouth syndrome is characterized by both positive (burning pain, dysgeusia
      and dysesthesia) and negative (loss of taste and paraesthesia) sensory symptoms
      involving the lips and tongue, mainly the tip and anterior two-thirds. BMS
      patients report a persistently altered (metallic) taste or diminished taste
      sensations. Acidic foods such as tomatoes and orange juice cause considerable
      distress. Most of the common laboratory tests suggested for BMS patients will be
      negative as well. BMS is best subcategorized as primary BMS, no other evident
      disease, and secondary BMS, which is defined as oral burning from other clinical
      abnormalities. The presence of BMS is very uncommon before the age of 30; 40
      years for men. The onset in women usually occurs within three to 12 years after
      menopause, and is higher in women who have more systemic disease. Quantitative
      assessment of the sensory and chemosensory functions in BMS patients reveals that
      the sensory thresholds (significantly higher) are different than in controls.
      Tongue biopsies have shown that there is a significantly lower density of
      epithelial nerve fibers for BMS patients than controls. The above data generally
      support the idea that BMS is a disorder of altered sensory processing which occur
      following the small fiber neuropathic changes in the tongue. BMS patients
      frequently have depression, anxiety, sometimes diabetes, and even
      nutritional/mineral deficiencies, but overall these co-morbid diseases do not
      fully explain BMS. The management of BMS is still not satisfactory, but because
      BMS is now largely considered to be neuropathic in origin, treatment is primarily
      via medications that may suppress neurologic transduction, transmission, and even
      pain signal facilitation more centrally. Finally, spontaneous remission of pain
      in BMS subjects has not been definitely demonstrated. The current treatments are
      palliative only, and while they may not be much better than a credible placebo
      treatment, few studies report relief without intervention.

PMID- 16967672
TI  - Orofacial muscle pain: new advances in concept and therapy.
AB  - This manuscript focuses on chronic myogenous pains affecting the masticatory
      muscles. The differentiation of myogenous masticatory pain into subcategories is
      proposed by separating myogenous pains according to their location and anatomic
      extent. Focal myalgia, regional myalgia, myofascial pain, and fibromyalgia are
      classified based on specific historical and clinical examination criteria. The
      probable mechanisms underlying chronic myogenous pains and trigger points
      phenomena are discussed. Treatment options of the myogenous masticatory pain
      conditions including physical medicine modalities, as well as several types of
      pharmacologic agents, are presented.

PMID- 16967673
TI  - Diagnostic imaging for chronic orofacial pain, maxillofacial osseous and soft
      tissue pathology and temporomandibular disorders.
AB  - Since dentists can be faced by unusual cases during their professional life, this
      article reviews the common orofacial disorders that are of concern to a dentist
      trying to diagnose the source of pain or dysfunction symptoms, providing an
      overview of the essential knowledge and usage of nowadays available advanced
      diagnostic imaging modalities. In addition to symptom-driven diagnostic dilemmas,
      where such imaging is utilized, occasionally there are asymptomatic anomalies
      discovered by routine clinical care and/or on dental or panoramic images that
      need more discussion. The correct selection criteria of an image exam should be
      based on the individual characteristics of the patient, and the type of imaging
      technique should be selected depending on the specific clinical problem, the kind
      of tissue to be visualized, the information obtained from the imaging modality,
      radiation exposure, and the cost of the examination. The usage of more
      specialized imaging modalities such as magnetic resonance imaging, computed
      tomography, ultrasound, as well as single photon computed tomography, positron
      electron tomography, and their hybrid machines, SPECT/ CT and PET/CT, are
      discussed.

PMID- 16967675
TI  - Medical management of oral motor disorders: dystonia, dyskinesia and drug-induced
      dystonic extrapyramidal reactions.
AB  - This article reviews three of the involuntary hyperkinetic motor disorders that
      affect the orofacial region, namely orofacial dystonia, oromandibular dyskinesia,
      as well as medication-induced extrapyramidal syndrome-dystonic reactions.
      Specifically, it discusses and contrasts the clinical features and management
      strategies for spontaneous primary and drug-induced motor disorders in the
      orofacial region. The article provides a list of medications reported to cause
      drug-related extrapyramidal motor activity above and beyond the more commonly
      known antipsychotics medications. It provides a needed update because the number
      and use of medications causing involuntary jaw muscle activity are increasing.
      For example, selective serotonin reuptake inhibitors (SSRI), stimulant
      medications and illegal drugs have all been reported to induce an orofacial motor
      activation as adverse reactions. This article also discusses briefly the genetic
      and traumatic events associated with spontaneous dystonia. Finally, this article
      presents an approach for management of the orofacial motor disorders that
      involves the following three steps: (1) collect a full clinical history and
      examination, including magnetic resonance imaging of the brain; (2) after ruling
      out CNS disease, adverse medications reactions and local pathology, try one or
      more of the motor-suppressive medications that may be helpful in these cases
      (e.g., cholinergic receptor antagonizers or blockers, and GABA-ergic including
      benzodiazepines); and (3) if the disorder is severe enough and focal enough to
      consider, and motor-suppressive medications are not adequate, then consider
      botulinum toxin injections. The contraindications, side effects, and usual
      approach for these medications and injections are discussed.

PMID- 16967674
TI  - Using oral medications, infusions and injections for differential diagnosis of
      orofacial pain.
AB  - Chronic orofacial pain is a rapidly evolving and challenging field that deals
      with the management of pain originating from neurogenic, osseous, muscular, or
      vascular structures of the head and neck. The challenge lies in the accurate
      diagnosis of orofacial pain conditions, which may be difficult to differentiate
      in many clinical situations. As pain cannot be "seen" or precisely located or its
      intensity measured with any device, clinicians must rely heavily on the patient's
      own description of type, duration and location of pain, and thus, history plays a
      crucial role in diagnosis. Advances in neuroscience, pharmacology, and pain
      management have made medications one of the primary therapeutic modalities in the
      management of pain including orofacial pain conditions. Despite this, these
      medications will not help patients if the origin and nature of pain is not
      accurately diagnosed. Hence, diagnosis is critical for successful management of
      orofacial pain conditions. Experience and knowledge of practice in pain
      management have led clinicians to devise several clinical diagnostic tests using
      medications in various forms (topical, oral, injections, intravenous infusions)
      to differentiate certain orofacial pain disorders where the nature of pain is
      unclear and the presentation of pain is at multiple sites. Although the
      diagnostic tests are not 100 percent accurate, they are very effective in many
      clinical scenarios, especially in orofacial pain conditions. Topical medications
      such as anesthetics and anti-inflammatories, oral medications such as anti
      inflammatory drugs and skeletal muscle relaxants, injections such as local
      anesthetics and corticosteroids, and vapocoolant sprays are some examples of the
      modalities used by clinicians to manage orofacial pain conditions. These
      medications may also be used for diagnostic tests to aid in accurate diagnosis of
      some orofacial pain conditions. In addition, there are special cases where
      medications such as triptans, carbamazepine and indomethacin may be used as
      diagnostic tests to confirm diagnosis of migraines, neuralgias, or stabbing
      headaches, respectively. Based on the concept of using medications to predict
      which treatment would be best for certain pain conditions or to aid in better
      diagnosis, diagnostic intravenous infusions of lidocaine, morphine, and ketamine
      have been studied to test the response to adjuvant analgesics and oral
      dextromethorphan. Paradoxically, taking the patients off their current
      medications can be of diagnostic significance in conditions like medication
      overuse headache and serotonin selective reuptake inhibitor-induced clenching. In
      summary, this paper focuses on the use of medications in different forms as
      useful diagnostic tests for differential diagnosis of orofacial pain conditions
      that are difficult to diagnose or are refractory to past or current treatment.

PMID- 16967677
TI  - Orthotopic liver transplantation in hepatocellular carcinoma: comparison of
      results in incidental and known hepatocellular carcinoma.
AB  - Liver transplantation (LTx) is known therapy for hepatocellular carcinoma (HCC).
      We undertook a retrospective chart review and analysis of our experience with 19
      patients with HCC who had undergone LTx between June 1995 and January 2003. We
      compared the results of 12 patients with known HCC (group I) with that of 7
      patients with incidental HCC (group II). We found that the incidence of
      multifocal disease, lymphatic involvement, and tumor-free survival was not
      significantly different between the two groups. One patient in group I died of
      tumor. Patient survival was better in group II (100%), with a median follow-up of
      45 months, as 4 more patients in group I (with known HCC) died of reasons
      unrelated to tumors, with a median follow-up of 23 months. We conclude that LTx
      in patients with either incidental or known HCC results in excellent tumor-free
      survival.

PMID- 16967678
TI  - Etiology of intestinal obstruction in patients without a prior history of
      laparotomy or a detectable external hernia on physical examination.
AB  - We evaluated the preoperative determination of the etiology and effectiveness of
      the diagnostic modalities, as well as the incidence of various causes of
      intestinal obstruction (IO) from 1981 through 2001 at a university-affiliated
      emergency center. Patients with a history of prior laparotomy or evidence of
      hernia on physical examinations were excluded. Eighty-three patients with
      surgically or endoscopically proven IO were reviewed. The most common cause of IO
      in the group with enteric obstruction was hernia while that in the group of
      colonic obstruction was carcinoma. Of the first preoperative diagnostic
      modalities to correctly determine the cause of obstruction, the most common were
      contrast enema and colonoscopy. Preoperative determination of the etiology was
      possible in 67% of the patients and was significantly more common in patients
      with colonic obstruction than in those with enteric obstruction.

PMID- 16967679
TI  - Medial hemisoleus muscle flap: a reliable flap for soft tissue reconstruction of
      the middle-third tibial wound.
AB  - Although the medial hemisoleus muscle has been considered a local reconstructive
      option for soft-tissue reconstruction of the middle-third tibial wound, its
      reliability and usefulness has been debated among plastic surgeons. This study
      reports one surgeon's experience with medial hemisoleus muscle flaps and shows
      their application for soft tissue reconstruction of middle-third tibial wounds.
      Over the past 2 years, 10 patients underwent soft tissue reconstruction of a
      middle-third tibial wound with a medial hemisoleus muscle flap and skin graft.
      The flap was elevated with emphasis on the preservation of as many perforators to
      the flap as possible while allowing adequate arch rotation of the flap to cover
      the exposed tibia and/or hardware. All patients were followed for up to 2 years.
      There was no total flap loss, and limb salvage was achieved in every patient in
      this series. Only two patients with peripheral vascular disease developed small
      partial but insignificant distal flap necrosis and were treated with debridement
      and flap advancement. The tibial wounds of all patients subsequently healed with
      excellent cosmetic outcome during follow-up. The results from this study indicate
      that the medial hemisoleus muscle flap is reliable for soft-tissue reconstruction
      of a middle-third tibial wound. Meticulous flap elevation with the preservation
      of perforators to the flap is the key for such success.

PMID- 16967680
TI  - Free jejunal autograft reconstruction after total pharyngolaryngeal resection.
AB  - A free jejunal autograft reconstruction after debulking high stage larynx and
      hypopharynx tumors has become a popular method in our 10-year experience. We
      retrospectively studied the efficacy and outcome. Nine patients (M/F, 8/1)
      underwent a total of 10 free jejunal autograft reconstructions. The median age
      was 58.6 years (range, 48-78 years). The median hospital stay was 32 days (range,
      13-67 days) and the graft failure rate was 10% (1/10), 9/10 successfully
      retransplanted. Postoperative mortality rate was 0%; one patient was lost during
      follow-up, one patient died of lung cancer, three died of local recurrence, and
      four patients have no evidence of disease at this moment (mean follow-up of 16.5
      months; range, 9-41 months). Salivation fistulas were present postoperatively in
      four patients: one closed spontaneously and three closed after surgery. In our
      hands, the free jejunal graft is the preferred method for single-stage
      reconstruction of circumferential defects of the gullet.

PMID- 16967681
TI  - Marjolin's ulcer arising from a laparostomy scar.
AB  - Marjolin's ulcer is the malignant transformation of a scar, usually as a squamous
      cell carcinoma. An uncommon presentation form is from a laparostomy scar. A 49
      year-old patient that had a laparostomy during the treatment of a
      necrohemorrhagic pancreatitis in 1987 complained 13 years later of a 20-cm ulcer
      on the laparostomy scar. A resection of the abdominal wall including the ulcer
      and a segmental transverse colectomy were performed because of infiltration by an
      invasive squamous cell carcinoma. Ten months later, axillary lymphadenectomy was
      performed because of lymph node metastasis. Currently, the patient is free of
      disease. Lymph node infiltration is frequent in squamous cell carcinoma on
      Marjolin's ulcer and survival is not good. Prophylaxis of this disease includes
      meticulous care of wounds, with early skin grafts when required and treatment of
      infections.

PMID- 16967682
TI  - Does truncal ligation of the inferior thyroid arteries during bilateral subtotal
      thyroidectomy affect serum calcium levels? A prospective, randomized, controlled
      study.
AB  - This study was designed to investigate the effect of truncal ligation of the
      inferior thyroid arteries on post-thyroidectomy serum calcium levels. This
      prospective, randomized study was carried out in 98 patients. In group 1,
      bilateral inferior thyroid arteries were ligated truncally during bilateral
      subtotal thyroidectomy procedure, whereas in group 2, ligation was not performed.
      In all patients, serum ionized calcium levels were measured preoperatively and on
      postoperative days 1, 2, 3 and 30. There were no statistically significant
      differences in serum ionized calcium values between group 1 and 2 on
      postoperative days 1, 2, 3, and 30 (P > 0.05). Laboratory hypocalcemia was found
      on postoperative days 1, 2, and 3 in 9 (9.2%), 15 (15.3%), and 2 (2.0%) patients,
      respectively. In all patients, laboratory hypocalcemia improved until
      postoperative day 5. It was thought that truncal ligation of the inferior thyroid
      arteries during bilateral subtotal thyroidectomy had no effect on post
      thyroidectomy serum calcium levels.

PMID- 16967683
TI  - Pelvic vascular prospects for uterine transplantation.
AB  - While developing the technique of abdominal radical trachelectomy for
      conservative cervical cancer management, the vascular supply of the uterus was
      thoroughly examined. This was a prelude to study the possibility of uterine
      transplantation where initial concerns were about how uterine artery anastomosis
      might be achieved and the subsequent function of these vessels in pregnancy. In
      experiment 1, the uterine arteries in two sows were divided and reanastomosed. At
      6 weeks, all sows including control were inseminated. After weaning 3 months
      after delivery, the sows were killed, and postmortem studies were undertaken.
      Successful reanastomoses of the uterine arteries were accomplished in both study
      sows. After insemination, pregnancy proceeded uneventfully, and both sows
      farrowed normally with average litter sizes. Histopathology of the uterine
      arteries revealed minimal intimal fibrosis across all anastomotic sites. Uterine
      artery anastomosis in the porcine model is feasible with subsequent normal
      vascular function in pregnancy of the anastomosed vessels.

PMID- 16967684
TI  - Pulse oximetry and perfusion index measurement to assess uterine perfusion and
      viability.
AB  - This study was designed to establish if pulse oximetry (O2Sat) and perfusion
      index (PI) could be used to assess the contribution that uterine and ovarian
      vessels make to the overall perfusion of the uterus. During routine
      hysterectomies, the O2Sat and PI were measured over the right and left uterine
      cornu. These measurements were taken before any vessels were ligated (baseline),
      after only the ovarian vessels were clamped and then after the uterine vessels
      were clamped. Clamping the ovarian vessels alone decreased the uterine O2Sat and
      PI by a statistically significant amount. Subsequent clamping of the uterine
      vessels produced further significant decreases in O2Sat and PI. We concluded that
      both pairs of vessels contribute almost equally to uterine perfusion and that
      there may be a role, particularly for O2Sat and possibly for PI variables, in
      determining the success of uterine and ovarian vessel reanastomosis in uterine
      transplantation.

PMID- 16967685
TI  - Liver abscess: a clinicopathological analysis of 82 cases.
AB  - Liver abscesses are a common pathology in India, but a strategy for effective
      treatment has not been established. Eighty-two patients with liver abscess were
      studied over a 4-year period. Clinical features, ultrasound findings, laboratory
      studies, and outcome of therapy were evaluated. Treatment options were
      antibiotics alone, needle aspiration, catheter drainage, or open surgical
      drainage; 51.2% of all abscesses were amebic, 23.2% were pyogenic, and 25.6% had
      unknown causes. A total of 75.6% of the abscesses were solitary, with 62.2%
      confined to the right lobe. Pyogenic abscesses were more likely to have anemia,
      leukocytosis, and deranged liver function. Amebic abscesses tended to have a
      larger volume. Patients undergoing catheter drainage showed a more rapid
      reduction in initial abscess volume, whereas resolution of the abscess cavity
      took longer with antibiotic therapy alone. Ultrasound-guided needle aspiration
      and catheter drainage are safe and effective in the management of liver abscess.
      Drug therapy alone may be useful only in select cases.

PMID- 16967686
TI  - Adenoid cystic carcinoma of the male breast.
AB  - We present an 82-year-old male patient who presented with complaints of gradually
      an increasing ulcero-proliferative lesion with persistent mucinous discharge in
      the left breast. Left side-modified radical mastectomy was done. This was
      histopathologically diagnosed as an adenoid cystic carcinoma of the left breast.
      Periodic acid schiff (PAS) staining confirmed the diagnosis. Three of the five
      axillary lymph nodes excised were positive for malignancy. Although the patient
      was advised to have postoperative radiotherapy, he did not comply. After 2 years,
      the patient again presented with local recurrence of the disease. Wide excision
      of the recurrent malignant nodules over the anterior chest wall was done, and the
      defect was covered primarily with split thickness skin grafting. Postoperative
      radiation was given. For the past 9 months, the patient has maintained a regular
      follow-up on an outpatient basis. He does not have any evidence of recurrence of
      the tumor--neither locally nor distant metastasis.

PMID- 16967688
TI  - The future of Texas dentistry challenges and opportunties, part II.

PMID- 16967687
TI  - Thyroid incidentalomas: prediction of malignancy and management.
AB  - The treatment strategy of an incidentally detected thyroid nodule is
      controversial. The aim of this study was to establish management criteria for
      thyroid incidentalomas by defining and formulating the risk factors predicting
      thyroid malignancy. A prospective database containing 815 consecutive patients
      who underwent a thyroidectomy for nodular thyroid disease, between January 1992
      and May 2003, was studied. Multivariate analyses demonstrated that the
      independent clinical predictors of malignancy were a fixed nodule and cervical
      lymphadenopathy on palpation, a euthyroid patient, and a patient age <23 years or
      >45 years; and independent nodule features significantly associated with
      malignancy were punctuate calcifications, irregular nodule margin, solid
      appearance on ultrasonography, and solitary nodule in an euthyroid patient. Using
      the regression coefficients of four independent ultrasound (US) features, a
      malignancy risk score of a nodule was calculated as follows. Depending on the
      score of a thyroid nodule, a simple follow-up, a US-guided fine needle aspiration
      biopsy or a thyroidectomy, may be offered for management.

PMID- 16967689
TI  - Who would've blamed a little piece of protein?

PMID- 16967690
TI  - Prions in dentistry--what are they, should we be concerned, and what can we do?

PMID- 16967691
TI  - A "right start" for children in the cities of Texas?

PMID- 16967692
TI  - Recommendations to improve the oral health of Texas seniors.

PMID- 16967693
TI  - Human--and porcine--dura mater linked to iatrogenic CJD.

PMID- 16967694
TI  - Increasing your practice with cosmetic dentistry.
AB  - Incorporate these guidelines into your practice, and utilize patient financing to
      maximize your treatment acceptance, and the cosmetic aspect of your practice will
      likely boom. No matter how much you want to do something, or how great your ideas
      are, if you aren't able to execute the project, nothing will happen. Plan.
      Prepare. Present. Persevere.

PMID- 16967695
TI  - Oral and maxillofacial pathology case of the month. Osteosarcoma (osteogenic
      sarcoma), high grade.

PMID- 16967696
TI  - [Comprehensive geriatric assessment in hospitalized patients aged 80 years and
      more].
AB  - Comprehensive geriatric assessment during hospitalization, taking into account
      the specificity of geriatric patients could be used both in acute and long-term
      care. We analyzed 63 patients aged at least 80 years, born on odd days and
      hospitalized at the Department of Internal Medicine and Geriatrics, University
      Hospital, Krakow. We examined patients using Geriatric Assessment Chart which
      consisted of Barthel Index (used to determinate motor activity), MMSE, GDS
      (Geriatric Depression Scale), abbreviated Tinetti Test, Waterlow Index (used to
      determine the risk of pressure sore development), delirium risk factors scale,
      and social evaluation. The data were analyzed according to sex, marital status,
      level of mood, and residence status (free living or institutionalized). The mean
      age of 47 women and 16 men was 85.0 +/- 4.34 years. Dementia was been found in
      60% of examined patients. Depression (usually mild) was encountered in 55.4%.
      Motor activity was moderately to severely impaired in the entire group, with high
      level of risk of falls and development of pressure sores. Thirteen per cent of
      the patients have been admitted with already developed ulcers. The results
      suggest the need for the comprehensive geriatric assessment both in hospitalized
      patients and in post-hospital phase of care.

PMID- 16967697
TI  - [Analysis of correlation between HPV DNA lymph node presence and pathologic
      parameters of primary tumour in cervical carcinoma patients treated surgically].
AB  - Young-age sexual activity, multiple sexual partners, number of pregnancies,
      smoking and human papilliomavirus (HPV) infections are factors commonly
      considered as promoters of cervical tumorogenesis. Cervical carcinoma patients'
      prognosis correlates significantly with staging (according to FIGO
      classification). In early stages lymph-node involvement is considered as the most
      important prognostic factor. Other factors are: initial volume of the lesion,
      lymphatic and blood vessels involvement, depth of cervical invasion. Also
      parametrium involvement seems to decrease the rate of 5-year survival. The aim of
      the research was to estimate correlation between HPV DNA lymph node presence and
      pathologic parameters of primary tumour in surgically treated cervical carcinoma
      patients. We analysed DNA isolated from lymph nodes sampled intra-operatively
      from 134 patients, surgically treated for cervical cancer with PCR. We confirmed
      the presence of HPV DNA sequences in lymph nodes in 81 (60.5%) cases. Lymph node
      presence of HPV DNA rate was significantly higher in: advanced tumours, cases
      with initial lesion volume exceeding 10 cm3, cases with uterus and vaginal
      involvement and with initial tumour invasion deeper than 10 mm.

PMID- 16967698
TI  - [Evaluation of the efficacy of long-acting somatostatin analog as adjunctive
      therapy in patients with active acromegaly].
AB  - Transsphenoidal surgery is the first-line therapy for patients with acromegaly,
      but can achieve biochemical control with normalization of somatomedin C in 40-80%
      of cases. All patients with continued growth hormone hypersecretion after
      neurosurgery require adjunctive therapy to prevent morbidity and premature
      mortality. The aim of our study was to evaluate the efficacy of long-acting
      somatostatin analog--octreotide LAR (OCT-LAR) as adjunctive therapy for patients
      with persistent disease. 14 adult subjects (age 45 +/- 15 years) were included
      into the study. All patients were diagnosed as having growth hormone secreting
      pituitary tumor and underwent transsphenoidal surgery (TSS). Radiotherapy (RT)
      was used as adjunctive therapy in 7 of investigated persons. In all subjects
      elevated level of somatomedin C was found, 9 have increased level of growth
      hormone (hGH) as well. After 6 months therapy with OCT-LAR we noticed drop in
      somatomedin C and hGH levels in all patients. Mean drop in somatomedin C level
      was 42.3% (p=0.001), in GH level was 52.3% (p=0.001). We found entire
      normalization of GH in 12 (85.7%) patients, nearly normalization of somatomedin C
      (level lower than 110% of normal upper limit) in 8 (57%) patients. We found no
      significant correlation between decrease in somatomedin C and its level prior to
      the treatment (p=0.8), but high positive correlation between decrease in hGh
      level and its initial value (R=0.75, p=0.002). Decreases in both somatomedin C
      (p=0.7) and hGH (p=0.6) levels were not correlated with patients' age. The
      therapeutic outcome defined as decrease in somatomedin C level was not
      significantly different between patients with or without adjunctive radiotherapy
      in the past (p=0.08) and between patients with intensive or weak isotope
      collection in the pituitary in 99mTc-octreotide scintiscan (p=0.2). CONCLUSIONS:
      Octreotide-LAR efficiently reduces somatomedin C and GH levels in patients with
      active acromegaly. Initial values of somatomedin C as well as age and isotopic
      imaging findings are not valuable predictor factors for therapeutic outcome.

PMID- 16967699
TI  - [Influence of hyperthyroidism defined as TSH serum level on QT corrected interval
      dispersion (QTcd)].
AB  - BACKGROUND: Electrocardiographic dispersion reflects the heterogenity of
      ventricular repolarisation. It has been suggested that changes QT dispersion in
      thyroid dysfunction can be prognostic factor of different arrhytmias aspecially
      ventricular arrhytmias. Calculation can be done from easy availabe tests such as:
      TSH serum level and resting electrocardiogram. AIM: The aim of the present study
      was to evaluate the prognostic value between TSH serum level, QT corrected
      interval value and corrected interval dispersion value.Are there any relationship
      between QTcd and TSH serum level. METHODS: From 314 person with hyperthyroidism
      included to the study group 46 patients with isolate hyperthyroidism whom have
      made TSH serum leve land resting electrocardiogram. In this group was 36 (78.3%)
      women and 10 (21.7%) men aged 38 to 78. The medium age was 52.3 +/- 9.9 years. To
      the observation include the patient with TSH level below 0,4 uU/ml in sreening.
      The results has been analysed in two subgroups: first A (1A)--high level
      hyperthyroidism (25 person; 18 women (72.0%), 7 men (28%); second B(2B)--low
      level hyperthyroidism (21 person; 18 85.7%)women, 7 men (14.3%). RESULTS: In
      hyperthyroidism group (1A+1B) with TSH serum level below 0.4 uU/ml QTc dispersion
      increase. Relation seems to be inversely proportional. The lower TSH serum level
      the higher percent increasing distance of QTcd, especially in high level
      hyperthyroidism subgroup(1A) with TSH seru level below 0.1 uU/ml. For QTcd > or =
      65 ms sensivity is 88.0%; specisicity is 42.9%. We didn't observe serious
      ventricular arrhytmias in the both subgroups. CONCLUSIONS: Indeed there is
      evidence that invesigating QT c interval dispersion (QTcd) in thyroid dysfunction
      may be a useful parameter in hyperthyroidism especially in high level
      hyperthyroidism subgroup (1A). The long QTcd suggest proarythmic susceptibility
      in this subjects subhyperthyroidism group with another risk stratification
      predicts increasing QTcd such as dyselectrolytaemia, previous myocardial infarct,
      coronary artery disease, diabetes, stroke or antyarrhytmic drugs.

PMID- 16967700
TI  - [Prevalence of Helicobacter pylori infection among children and youth with acid
      gastroesophageal reflux].
AB  - AIM: The aim of the study was to estimate the prevalence of Helicobacter pylori
      infection in patients with acid gastroesophageal reflux. PATIENTS NAD METHODS:
      Analysis of medical records of 160 children and youth admitted to the hospital
      between October 2003 and December 2004 was performed. All of these patients were
      diagnosed for acid gastroesophageal reflux due to clinical features and results
      of oesophageal pH-metry. During routine diagnostic procedures of abdominal pain,
      vomiting, nausea and other non-specific symptoms, endoscopy of upper
      gastrointestinal tract was simultaneously performed. Helicobacter pylori
      infection among analysed patients was diagnosed due to histopathological studies
      of specimens sampled during endoscopy and positive urease test. RESULTS: Analysed
      group included 75 girls and 85 boys between 12 month old and 18 years old (mean
      age 8.47). Helicobacter pylori infection was observed in 29 patients (18.1%) of
      160 analysed cases. Mean age of patients with H. pylori infection was 11.83
      years, whereas mean age of patients without H. pylori infection was 7.72 years.
      Oesophagitis was presented in 28 (17.4%) of all patients. In the group with H.
      pylori infection oesophagitis was observed only in 4 patients (13,8%). In the
      group without H. pylori infection oesophagitis was presented in 24 patients
      (18,3%). CONCLUSIONS: 1. Prevalence of Helicobacter pylori infection among
      patients with acid gastroesophageal reflux was lower than prevalence of infection
      in children and youth population of Kujawsko-Pomorski region. 2. Helicobacter
      pylori infection among children and youth with acid gastroesophageal reflux
      doesn't influence the prevalence of oesophagitis.

PMID- 16967701
TI  - [Vitamin B-6 in chronic renal insufficiency].
AB  - Chronic diseases, including chronic renal insufficiency, predispose to deficiency
      of vitamin B-6. Prevalence of that phenomenon, the need and appropriate level of
      supplementation remain controversial. The paper is a review of literature
      concerning those topics. Causes of deficiency, as well as advantages and dangers
      of supplementation were referred.

PMID- 16967702
TI  - [Cachexia in chronic cardiac disease. Ancient syndrome new idea?].
AB  - Cachexia has long been recognized as serious complication of chronic illness.
      Cardiac cachexia is a syndrome of generalised wasting which carries a poor
      prognosis of the chronic heart disease. Characteristic features of cachexia
      include the activation of the immune system associated with raised plasma
      concentriations of tumor necrosis factor alpha (TNF(alpha) and other plasma
      cytokines. Another crucial issue is muscle wasting through the ubiquitin
      proteasome pathway. The prevention or attenuation of disease related skeletal
      muscle degeneration has been a common goal in the treatment of cardiac cachexia.

PMID- 16967704
TI  - [Solitary fibrous tumor of the pleura (SFTP) hidden in the pleural effusion].
AB  - The patient with a non-malignant type of solitary fibrous tumor of the pleura
      (SFTP) has been presented as an example; this tumor manifested itself in long
      lasting pleural effusion. The tumor, submerged in the liquid, with the diameter
      of 16 cm, was invisible in standard and computer X-rays of the chest. The tumor
      was found and removed during the thoracotomy. The patient has been alive for 9
      years, without symptoms of the disease since the operation was performed.
      CONCLUSIONS: 1. The source of one-sided exudation can be a non-malignant SFTP. 2.
      Tumor submerged in the liquid can be invisible on standard and computer pictures
      of the chest.

PMID- 16967703
TI  - [VEGF and its receptors as therapeutic target in cancer therapy].
AB  - Vascular endothelial growth factor is the main mediator of angiogenesis. For the
      time being five members of VEGF familly have been discovered and marked A to E.
      First of them VEGF-A, previously named vascular permeability factor, possesses
      five isoforms. Some of them are connected to extracellular matrix, other are
      soluble. Two isoforms of VEGF-B are also distinguished. VEGF-A and VEGF-B play
      major roles in angiogenesis as ligands of tyrosine activity receptors: VEGFR-1
      and VEGFR-2. VEGF-C and VEGF-D are responsible for lymphangio-genesis as VEGFR-3
      ligands; however VEGF-C being related to the second receptor may also influence
      angiogenesis. The least known is the function of VEGF-E. Angiogenic factors are
      attractive targets for cancer therapy because of inhibition of VEGF functions
      they cause "dormic tumors". Nowadays research of several inhibitors of
      angiogenesis takes place, and some of them have already reached the third phase.

PMID- 16967705
TI  - [Cutaneous melanoma during pregnancy--a case report].
AB  - Cutaneous melanoma is a tumour which has the highest increase of incidence per
      year. In Poland, the process reaches 10%. In this essay, a case of cutaneus
      melanoma co-existing with pregnancy was presented. The woman was 36 years old.
      The neoplasm was diagnosed during the eighth week of her second pregnancy. An
      excision biopsy of the skin lesion on the back surface of the left shank was
      carried out. III degree melanoma malignum according to Clark's, and 1,6 mm
      according to Breslov was diagnosed. During the 35th week of pregnancy, the woman
      was hospitalized because of threatening premature labour. During her stay at the
      department, enlarged inguinal lymph nodes were observed. Because of the advanced
      pregnancy, the patient was qualified to limfadectonomy after labour. In the 38th
      week of pregnancy, she delivered by spontaneous labour a healthy baby. After two
      weeks, an inguinal limfadectonomy was carried out. In the histopathological
      analysis, metastases to lymph nodes were diagnosed. They did not cross the
      nodular capsules. The patient remains under monthly oncological observation.
      Eight months after delivery, thirteen months from the removal of the primary
      lesion, no lesions in the physical examination and other additional examinations
      have been diagnosed. The accurate evaluation of the pigmented nevus appearance
      could contribute to the diagnosis of the melanoma in the early stage of
      progression. Pregnant women, who notice a change in the look of a nevus should be
      directed to a dermatological consultation.

PMID- 16967706
TI  - [What Edmund Modrzejewski (1849-1893) contributed to the Polish otiatrics?].
AB  - The professional and scientific activities in the area of otiatrics of Edmund
      Modrzejewski (1849-1893) are presented. Modrzejewski's education in otology in
      Vienna and other places is strongly pointed out. His achievements in the
      treatment of many diseases of the ear are depicted. Modrzejewski is shown as a
      one of the pioneer of treatment of deaf-mutism in Polish territories. His
      publishing activity is also depicted.

PMID- 16967707
TI  - Early pharmacological intervention in newly diagnosed metabolic syndrome and type
      2 diabetes.

PMID- 16967708
TI  - Economics of type 2 diabetes prevention.

PMID- 16967709
TI  - [Echocardiographic picture of Polish Olympic Team--Athens 2004].
AB  - Echocardiography is the basic, non-invasive diagnostic method in assessment of
      heart's structure and function in elite athletes. The aim of a study was to
      assess the heart's structure and function of Olympic-class athletes, enduring
      intensive training in log-term. An attempt was also made to compare types of
      physiological heart hypertrophy after extreme physical exercise load depending on
      gender and sport discipline. MATERIALS AND METHODS: 79 athletes (24 women and 55
      men) aged 19-37 (median of 26) took part in the study, they represented wide
      range of sports. In all cases single transthoracic echocardiography was
      performed. Body surface area was considered for better comparison of outcomes.
      RESULTS: High percentage of results exceeded echocardiographic norms for general
      population. In case of LVEDd (left ventricle end diastolic diameter) it was 27.8%
      of examined, for LA (left atrium) 32.9%, for RV (right ventricle) 84.8%, 53.2%
      for IVSd (interventricle sept diameter) and 11.4% for Ao (aorta diameter). Some
      of results exceeded also norms used in sport medicine. In 6.3% examined "sport"
      norms for IVSd were exceeded and in 19.9% for LV relative wall thickness (RWT).
      Higher than trace mitral valve insufficiency was observed in 6.3% cases, while in
      tricuspid valve this fraction reached 25%. Only in males the trace aortic
      insufficiency was observed (7% of all examined). 53% examined exceeded norm's
      range for E/A proportion (E/A >2). Significant differences in adaptive heart
      hypertrophy were observed between men and women and between athletes from sport
      disciplines with different static exertion load. These differences included both
      morphology and valve function. CONCLUSION: (1) Adaptive heart hypertrophy
      observed in echocardiography in Olympic-class athletes exceeds not only the norms
      for general population but also norms used in sport medicine. (2) Adaptive heart
      hypertrophy in female elite athletes leads to more eccentric type of remodelling
      then in men. (3) High static exertion load in performed sport is connected with
      concentric type of heart remodelling and with significant differences in systolic
      and diastolic parameters. (4) Considering body surface area allows a proper
      comparing of morphologic parameters between different genders and athletes
      practicing different sport disciplines.

PMID- 16967710
TI  - [Antiheparin activity of the aneurysm wall and parietal thrombus and blood plasma
      of patients with aortic aneurysm].
AB  - Aneurysm dilatation is filled by parietal thrombus. Its magnitude is determined
      by the ratio of coagulative to anticoagulative activities above all. The aim of
      the study was to assess antiheparin activity, contents of heparin neutralizing
      chemical compounds and glycosaminoglycans with anticoagulative activity as well
      in the aneurysm wall, parietal thrombus filling the aneurysm dilatation and blood
      plasma/blood serum of patients with aortic aneurysm. The studied material
      consisted of aneurysm walls and parietal thrombi extracts, as well as of blood
      plasma/serum of patients with aortic aneurysm. Extracts of normal aorta from
      organ donors and blood plasma/serum of healthy subjects were the control
      material. Antiheparin and antithrombin III activities, as well as contents of
      heparin neutralizing compounds and heparin-like acting glycosaminoglycans were
      evaluated in the investigated material with chemical methods. The aneurysm wall,
      parietal thrombus filling the aneurysm dilatation and blood plasma of patients
      with aortic aneurysm show high antiheparin activity and increased content of
      heparin neutralizing compounds. However differences in glycosaminoglycans content
      were not demonstrated. That can predispose to formation and enlargement of
      parietal thrombus in aneurysm dilatation.

PMID- 16967711
TI  - [Diagnosis and operative treatment cavernous angiomas of the central nervous
      system].
AB  - Among all detected cerebral angiomas the frequency of cavernous angiomas (CAs) is
      5-13%. The aim of this study is to present the diagnostic methods of CA of the
      central nervous system (CNS), indications for surgery and assessment of its
      outcome. Between 1993-2000, eleven cases of CAs were operated on at the
      Department of Neurosurgery, Medical College, Jagiellonian University in Krakow.
      In 6--seizures were observed, in 4--headache (supratentorial CAs), increasing
      neurological deficits in 4 (location in vertebral channel and cerebellum),
      hemorrhage--1 case (CA in pons combined with supratentorial lesion). Surgery was
      carried out by means of craniotomy, and via laminectomy in the cases of spinal
      channel tumours. Early and late outcome were assessed in following cathegories:
      very good, good, fair, bad (significant deterioration). The shortest late
      observation was 5 years. Direct very good surgical outcome was attained in 4
      cases (36%), good in 4. (36%), fair in 2. (18%), bad in 1 case. In late
      observation, 7 patients were very good (64%), and 3 good (27%). In one case the
      neurological improvement was poor, later observed--late outcome was fair. In 6
      cases they suffered from frequent epileptic seizures before surgery; they were
      seizure free in the late assessment. CONCLUSIONS: (1) direct surgical outcome in
      CA of the CNS is good and very good in the majority of cases; (2) in late
      observation, further neurological improvement allows to attain over 90% good and
      very good outcomes; (3) the high antiepileptic effectiveness after surgery of CA
      is observed.

PMID- 16967712
TI  - [New horizons for increased sensitivity of radionuclide imaging in primary
      hyperparathyroidism].
AB  - The aim of the study was to evaluate the impact of therapy with biphosphonates in
      patients with primary hyperparathyroidism and negative result of parathyroid
      scintigraphic imaging on increase of diagnostic sensitivity in repeated scans.
      Three female patients with diagnosed primary hyperparathyroidism and negative
      parathyroid imaging with subtraction 99m-Tc-MIBI scintigraphy were included into
      this prospective study. Patients had been receiving 70 mg of sodium alendronate
      orally, once a week for 3 months. After this period they were reevaluated with
      parathyroid subtraction scintigraphy. In all three patients a solitary area of
      uptake was found in the repeated scans. Patients were qualified for minimally
      invasive video-assisted parathyroidectomy. In two of them the repeated scans
      after treatment with biphosphonates were found to be true positive and in those
      two patients a solitary parathyroid adenoma was removed with video-assisted
      technique. In one patient a multiglandular disease was revealed intraoperatively
      basing on intraoperative iPTH assay and in that patient a subtotal video-assisted
      parathyroidectomy has been successfully completed. All three patients have been
      eucalcemic within the 6-months follow-up with iPTH serum values within the
      reference range. In conclusion, treatment with oral biphosphonates in patients
      with primary hyperparathyroidism and negative result of radionuclide parathyroid
      imaging, results in increased diagnostic sensitivity of repeated scans. This
      allows for successful minimally invasive parathyroid surgery in this group of
      patients with a predominant solitary parathyroid adenoma.

PMID- 16967713
TI  - [The laryngological and neurological aspects of dysphagia].
AB  - Swallowing is a complex motor event that is difficult to investigate in man. A
      slowed ability to eat a meal, loss of salivary control with drooling, episodic
      coughing, and choking and nasal regurgitation occurred due to the dysphagia.
      Swallowing disorders can be divided into oropharyngeal dysphagia and oesophageal
      dysphagia. The most common cause of oropharyngeal dysphagia is cerebrovascular
      accidents; other causes may include oropharyngeal structural lesions, systematic
      and local muscular diseases, and diverse neurologic disorders. Oesophageal
      dysphagia may result from neuromuscular disorders, mobility abnormalities, and
      intrinsic or extrinsic obstructive lesions. Initial evaluation of patients with
      suspected oropharyngeal dysphagia includes patient history, laryngological and
      neurological examination, and careful videofluoroscopic study of pharyngeal
      dynamics. Initial evaluation of patients with suspected oesophageal dysphagia
      includes patient history and barium swallow with oesophagography. Classifying
      dysphagia as oropharyngeal, oesophageal and obstructive, or neuromuscular symptom
      complexes leads to a successful diagnosis in 80% of patients.

PMID- 16967714
TI  - [Early laboratory markers of acute renal failure].
AB  - Acute renal failure is a sudden clinical condition caused by loss of renal
      ability to maintain homeostasis. Despite significant advances in renal
      replacement therapy--the mortality rate in ARF patients is still very high-
      ranging from 20% to 50%. Differential diagnostics, especially between acute
      prerenal and intrinsic acute renal failure is an extremly important stage in
      patient evaluation process. In the article--the authors present a short and
      concise profile of novel, more and less promising for future diagnostic ARF
      biomarkers: neutrophil gelatinase associated lipocalin (NGAL), sodium/hydrogen
      exchanger isoform 3 (NHE3), human kidney injury molecule-1 (hKIM-1), interleukin
      6 (IL-6), interleukin 8 (IL-8), interleukin 18 (IL-18), urinary cysteine-rich
      protein (Cyr 61), urinary glutathione-S-transferase (GST), cystatin C,
      spermidine/spermine N-acetyl transferase (SSAT) and actin) which are recently
      either in the animal model research stage or during preliminary clinical studies.
      Extension of research and wideninig of knowledge about the discussed novel, early
      markers of ARF--would permit for quicker introduction of specifically guided
      therapy and might improve the prognosis of ARF patients in the near future.

PMID- 16967715
TI  - [Prenatal ACTH-depot therapy].
AB  - ACTH-depot therapy is one of the therapeutic methods in threatening abortion or
      premature labor, introduced by Prof. R. Klimek in the 60-ies of the last century.
      Administration of syntetic ACTH is the method of first choice in treatment of
      neuroendocrinologically complicated pregnancy, safe for mother as for infant. The
      first trials of application of this method disclosed good results determined by
      very high birth rate of at term pregnancies (96%) and delivery of live infants,
      in comparison to 18.5% or 37% supported pregnancies treated conservatively, in
      the same group of women previously. Because hypothalamic hormones induce
      synthesis of enzyme-oxytocinase, it becomes possible to observe the development
      of pregnancy in women treated with ACTH-depot by CAP-level determination. In
      women with hypothalamic hypofunction, level of oxytocinase is low, increasing
      slowly, sometimes even its decrease is observed. Current multiple ACTH-depot
      doses: 0.5 mg i.m. are routinely used, instead of hitherto applied series of 3
      injections in the second and third trimester. Number of doses depend on: levels
      of oxyto-cinase, rate of its increase, reactivity of patient and progression of
      pregnancy. Administration of ACTH-depot seems to be more beneficial than
      aministration of corticoids, because this hormone does not cross the placenta,
      but increases the production of endogenic hormones. Unwelcome symptoms of ACTH
      depot treatment are similar to those observed in course of the corticold therapy,
      but they are less expressed. Development of features connected with
      hypercatabolism of proteins like: muscular atrophy, striae and osteoporotic
      changes, are not observed. Only single therapy with ACTH-depot causes regression
      of clinical symptoms of threatening premature labor, without necessity of
      tocolitic treatment. Thanks to steroidogenesis, normalisation of the number of
      preterm labors and respiratory disorders decreases.

PMID- 16967716
TI  - [Nonalcoholic steatohepatitis--current treatment options].
AB  - Nonalcoholic steatohepatitis (NASH) is the term used to describe the distinct
      clinical entity in which the liver biopsy findings are similar to that observed
      in alcoholic hepatitis, but patients lack a history of significant alcohol
      consumption. The most widely supported theory implicates insulin resistance as
      the key mechanism leading first to hepatic steatosis, and next to
      steatohepatitis. In spite of lacking proof by EBM (evidence based medicine) and
      effective therapy for NASH, modification of risk factors, such as obesity,
      hyperlipidemia, and good diabetic control is generally recommended. Although
      there is no consensus of treatment form, the new drugs which can be useful in
      NASH treatment are continously tested. The aim of our study is to present current
      knowledge about nonalcoholic steatohepatitis, focusing on present and being in
      various phases of clinical trials treatment options.

PMID- 16967717
TI  - [Pharmacological effects of flavonoids from Scutellaria baicalensis].
AB  - Scutellaria baicalensis is a plant widely used in Chinese and Japanese herbal
      medicine. Dry roots of Scutellaria baicalensis are used, especially as alcohol
      extracts. Flavonoids isolated from Radix Scutellariae have beneficial effects in
      hepatitis. Flavonoids derived from Scutellaria baicalensis produce antioxidative,
      antineoplastic, cardiomiocyte-protective activity. They inhibit agregation of
      platelets, permeability of capillary vessels, have antibacterial and anty
      angiogenic effects.

PMID- 16967718
TI  - [Acute toxoplasmic perimyocarditis in a 67-year-old HIV-negative woman--a case
      report].
AB  - Acquired toxoplasmosis is a widespread parasitic disease caused by an obligate
      intracellular protozoan, Toxoplasma gondii. Humans are infected by consuming
      undercooked or raw meat containing tissue cysts or by ingesting oocysts in food
      or water contaminated with feline faeces. Most cases of Toxoplasma gondii
      infections in immunocompetent individuals are asymptomatic. Although acquired
      toxoplasmosis is usually a mild infection, it may be life-threatening in
      immunocompromised patients. In this report we present a 67-year-old HIV-negative
      woman with acute toxoplasmic perimyocarditis, heart failure and with a history of
      ischemic heart disease, hypertension and dyslipidemia. The diagnosis was based on
      clinical characteristics, echocardiographic examinations, elevated inflammatory
      markers and the presence of IgM and IgG antibodies against Toxoplasma gondii. We
      conclude that Toxoplasma gondii infection should be considered in each case of
      perimyocarditis with concomitant, significant diagnostic and therapeutic
      problems, especially in immunocompromised patients. This paper also reviews
      differential diagnosis of elevated CA 125 serum levels in postmenopausal women.

PMID- 16967719
TI  - [Bourneville-Pringle disease. Case report].
AB  - We present a case of a 47-year-old woman suffering from Bourneville-Pringle
      disease and uterus cancer undergoing radical operation. Surgery was performed
      under general anaesthesia and went uneventfully.

PMID- 16967721
TI  - FAQs: neurological illness and driving.

PMID- 16967720
TI  - [A case of GH and TSH secreting pituitary macroadenoma].
AB  - A case of GH and TSH secreting pituitary macroadenoma is reported. A 45-year-old
      female presented clinical features of acromegaly (the abnormal growth of the
      hands and feet, with lower jaw protrusion), diabetes mellitus, hypertension,
      nodular goiter and hyperthyroidism of unclear origin. NMR pituitary imaging
      revealed intra and extrasellar tumor. The laboratory examinations showed very
      high plasma levels of GH and IGF-1 and normal level of TSH coexisting with high
      plasma levels of free thyroid hormones. Pharmacological pretreatment with
      somatostatin analogues caused the substantial reduction of GH and TSH plasma
      levels. Histological and immunohistochemical examination of the tissue obtained
      at transsphenoidal surgery showed GH and TSH secreting adenoma. The laboratory
      examinations after surgery showed normal GH and IGF-1 plasma levels and reduced
      insulin requirement, what indicates radical operation. The very low plasma levels
      of TSH and free thyroid hormones after surgery and immunohistochemical
      examination suggest central hyperthyroidism due to TSH secreting pituitary tumor
      (thyrotropinoma).

PMID- 16967722
TI  - Caring for patients with migraine.

PMID- 16967723
TI  - Managing neurological problems in heavy drinkers.

PMID- 16967724
TI  - Eczema: an essential picture guide for GPs.

PMID- 16967725
TI  - Managing scoliosis in adolescents.

PMID- 16967727
TI  - Private sector nurse training set to grow.

PMID- 16967728
TI  - The NHS needs a culture change to cope with patient choice.

PMID- 16967729
TI  - Raising the status of stroke.

PMID- 16967730
TI  - Streets ahead. Interview by Jennifer Taylor.

PMID- 16967731
TI  - Helping children cope with a debilitating disorder. Interview by Clare Lomas.

PMID- 16967732
TI  - A mental health worker for minority ethnic communities.
AB  - The Mental Health Workforce Strategy for England outlined a commitment to ensure
      that the mental health workforce had the skills, capabilities and capacity to
      meet the needs of people with mental health problems. One of its commitments
      involves creating new roles, including the community development worker for black
      and minority ethnic communities. This article outlines the key components of the
      role and how it is intended to ensure the mental health needs of black and
      minority ethnic communities are met.

PMID- 16967733
TI  - Tracheal intubation.

PMID- 16967734
TI  - Improving the care of dying patients in the community.
AB  - Palliative care services provided by the primary sector have changed considerably
      over recent years and patients and carers want choice over end-of-life care. In
      response to this need, the Macmillan Gold Standards Framework has been introduced
      and funded by the NHS as its chosen end-of-life programme. Clinical experience
      suggests the framework provides a better quality of care, improves staff morale
      and patient satisfaction, and reduces hospital and hospice occupancy.

PMID- 16967735
TI  - A patient satisfaction survey of a nurse-led colorectal clinic.
AB  - A new service was set up to achieve government targets to see patients with signs
      or symptoms of a possible colorectal cancer within two weeks of referral from
      their GP. The new clinics were nurse-led. A patient satisfaction survey was used
      to assess patients' opinions about the clinic. The results showed patients had a
      positive view of the clinic.

PMID- 16967736
TI  - Work relationships between agency and permanent staff.
AB  - AIM: To explore the nature of the relationship between agency workers and
      permanent staff within care homes. METHOD: A qualitative design was used with an
      interpretative phenomenological analysis. RESULTS: Four key themes were
      identified: issues about the psychological contract of agency workers; agency
      stigmatisation; issues on both sides of the relationship; and power and shifts in
      attitude. CONCLUSION: This study builds on our psychological understanding of
      workplace practices and relationships between agency and permanent staff. It
      should enable practical and effective improvements to be made to the quality of
      working life and self-identity of all who work in care homes.

PMID- 16967737
TI  - Changing food preference as a function of mood.
AB  - The authors investigated the effect of mood on food selection. Participants (N =
      98) indicated the likelihood of general eating and the likelihood of eating
      specific foods after reading and projecting themselves onto the events and
      emotions described in a sad and a happy vignette. Both men and women believed
      they were more likely to consume food following a happy versus a sad event, and
      men believed they were significantly more likely to eat than did women. However,
      the type of food men and women believed they would consume interacted with the
      type of event experienced. Vegetarian snack foods were more likely to be consumed
      following a happy versus a sad event, with men more likely to eat snack foods.
      Men did not significantly change in likelihood of consuming sweet foods as their
      mood changed. However, women believed they were more likely to consume sweet
      foods following a sad event. The authors discuss the results in terms of a self
      medication hypothesis and the effect of carbohydrates on central serotonin and
      endogenous opioids. Overall, results demonstrated that mood influences belief in
      the likelihood of food selection.

PMID- 16967738
TI  - Self research in educational psychology: a cautionary tale of positive psychology
      in action.
AB  - Recent calls for a positive psychology that would deemphasize human pathology and
      dysfunction in favor of building an understanding of positive features of human
      life and human flourishing make two assumptions that the author questions in this
      article. First, he challenges the assumption that disciplinary psychology has
      been fixated on pathology and dysfunction by considering work in educational
      psychology that, both historically and currently, espouses the characteristics of
      positive psychology as articulated by its major advocates. Second, through a
      brief, critical consideration of research on the self in educational psychology,
      he contests the assumption that psychology has sufficient resources to develop
      into the positive psychology envisioned by its promoters. He argues that
      psychology's emphasis on the individual, whose core self resides in a deep,
      internal psyche, radically strips psychology of the historical and sociocultural
      resources that enable self-development, constrain self-understanding, and
      constitute the self.

PMID- 16967739
TI  - Contribution of religiousness in the prediction and interpretation of mystical
      experiences in a sensory deprivation context: activation of religious schemas.
AB  - M. A. Persinger (2002) claimed that transcranial magnetic stimulation with weak,
      complex magnetic fields evokes mystical experiences. However, in a double-blind
      experiment, P. Granqvist, M. Fredrikson, P. Unge, A. Hagenfeldt, S. Valind., et
      al. (2005) found no effects of field exposure on mystical experiences (N = 89),
      though a minority of participants reported spontaneous mystical experiences.
      Following the conclusion of null effects from magnetic field exposure, the setup
      of this experiment, including pre-experimental assessments of religiousness and
      sensory deprivation, can be viewed as a prime/setting for such experiences. The
      authors analyzed subsets of experimental data from P. Granqvist and colleagues
      with emphasis on the contribution of religiousness in the prediction and
      interpretation of mystical experiences. They found that a higher degree of
      religiousness predicted a higher occurrence of mystical experiences with a
      religious quality, but not of mystical experiences without such a quality. The
      authors discuss findings in terms of the experimental setup serving as a
      prime/setting activating the religious schemas of religious participants.

PMID- 16967740
TI  - The Music Experience Questionnaire: development and correlates.
AB  - The authors introduce the Music Experience Questionnaire (MEQ), a self-report
      measure of individual differences in reactions to music. In analyses of responses
      in a derivation sample of 211 undergraduates and a replication sample of 105
      undergraduates, scores on the 6 scales of this measure showed acceptable alpha
      coefficients and test-retest correlations. The authors found 2 principal factors:
      subjective/physical reactions to music and active involvement. MEQ scores were,
      at most, weakly correlated with 2 measures of favorability of self-presentation,
      the Marlowe-Crowne Social Desirability Scale (D. P. Crowne & D. Marlowe, 1960)
      and the Responding Desirability on Attitudes and Opinions Scale (K. Schuessler,
      D. H. Hittle, & J. Cardascia, 1978). Examination of correlations between MEQ
      scores and the Center for Epidemiological Studies Depression scale (L. S.
      Radloff, 1977), as well as factor scores on the Adjective Check List (H. G. Gough
      & A. B. Heilbrun, 1983), suggested areas of similarity and difference in the
      correlates of music experience for women and men. The authors discuss directions
      for future research as well as potential uses of the MEQ.

PMID- 16967742
TI  - Integrating situational and dispositional determinants of job satisfaction:
      findings from three samples of professionals.
AB  - Job satisfaction can be conceptualized as a function of situational conditions,
      personal characteristics, and interactions between both groups of variables. The
      authors compared the relative predictive power of these determinants in 3 samples
      of professionals (total N = 1,065). Perceived job characteristics (qualification
      possibilities, social support, stress, autonomy, participatory leadership)
      uniquely explained 7-22% of the variance in job satisfaction, and dispositional
      factors (Big Five, occupational self-efficacy, work centrality, mastery goals)
      uniquely explained 8-12% of the variance. Dispositional influences were partially
      mediated by perceived job characteristics. Interactions between situational and
      dispositional factors were of little significance. The authors concluded that
      perceived job characteristics (especially autonomy and participatory leadership)
      are important determinants of job satisfaction, and neuroticism is an important
      determinant as well. Highly educated professionals' job satisfaction also seems
      to be driven by qualification possibilities.

PMID- 16967741
TI  - A bird in hand: discouraging gambling on a slot machine simulation.
AB  - Using a slot machine simulation, our laboratory has found that participants,
      given the opportunity not to gamble and to keep the money they have been staked,
      almost always choose to play the simulation. In this study, the authors
      investigated whether increasing the salience of the money for which participants
      played or increasing the response effort required to gamble the money would
      decrease gambling. In Experiment 1, participants in different groups were told
      about, were shown, or held the dollars 10 they were to be staked to play the
      simulation. Results showed that participants who held the money prior to gambling
      played fewer trials and bet less money than participants in other groups. In
      Experiment 2, participants in different groups were staked with dollars 5 in
      nickels, quarters, or their choice of nickels or quarters. Results showed that
      the participants staked with nickels ultimately gambled a similar amount of money
      as did participants staked with quarters. They did so by playing the simulation
      more times than the other participants. Participants staked with nickels did,
      however, end the session with the most money. Findings suggest ways that gambling
      and gambling losses can be lessened.

PMID- 16967743
TI  - What determines the public's health?

PMID- 16967744
TI  - Physical activity and ethnicity: evidence from the Canadian Community Health
      Survey.
AB  - BACKGROUND: A large proportion of the Canadian population lives a sedentary
      lifestyle. Few data are available describing the physical activity behaviours
      among specific ethnic groups in Canada, so the purpose of this study is to
      examine the relationship between ethnicity and the level of self-reported
      physical activity. METHODS: Pooled data from cycles 1.1 (2000/01) and 2.1 (2003)
      of the cross-sectional Canadian Community Health Survey (ages 20-64 yrs; N =
      171,513) were used for this study. Weighted prevalences of self-reported leisure
      time moderate (> or = 1.5 kcal x kg(-1) day(-1) (kkd)); moderate to high (> or =
      3 kkd) and high physical activity (> or = 6 kkd) were calculated, and multiple
      logistic regression models were used to quantify the odds of being physically
      active across ethnic groups, after adjustment for several covariates (White
      referent group). RESULTS: The rank order of prevalence of being moderately
      physically active by ethnicity was: White (49%), Other (48%), NA Aboriginal
      (47%), Latin American (40%), East/Southeast Asian (39%), Black (38%), West
      Asian/Arab (36%), South Asian (34%). Aboriginal men and women had the highest
      prevalences of being physically active at > or = 3 kkd (M = 32%, F = 22%) while
      East/Southeast Asian (19%) and East Asian/Arab men (19%), and South Asian women
      (12%) had the lowest prevalences. After accounting for covariates, Aboriginal men
      were at elevated odds of being physically active compared to Whites (> or = 3
      kkd, OR=1.6, p < 0.05; > or = 6 kkd, OR = 2.7, p < 0.05). Only 7% and 3% of
      Canadian men and women, respectively, were active at > or = 6 kkd. CONCLUSION:
      These results suggest that the prevalence of physically active Canadian adults
      varies by ethnicity. Strategies to promote physical activity and prevent physical
      inactivity should consider these findings.

PMID- 16967745
TI  - Physical activity and immigrant status: evidence from the Canadian Community
      Health Survey.
AB  - BACKGROUND: The immigrant population in Canada is diverse and growing, yet little
      is known about their physical activity behaviour and how it changes as they adapt
      to a Canadian lifestyle. This study extends the surveillance of physical activity
      in Canada to include the influence of time since immigration within and between
      ethnic groups. METHODS: Pooled data from cycles 1.1 (2000/01) and 2.1 (2003) of
      the cross-sectional Canadian Community Health Survey (ages 20-64 y; N = 171,513)
      were used for this study. Weighted prevalences of self-reported leisure-time
      physical activity (> or = 3 kcal x kg(-1) x day(-1) (kkd)) were calculated, and
      unadjusted and adjusted (age, income, education, BMI) multiple logistic
      regression models were used to quantify the odds of being physically active (PA)
      (> or = 3 kkd) by time since immigration (recent immigrant < or = 10 yrs,
      immigrant >10 yrs, non-immigrant) within and between ethnic groups (White
      referent group). RESULTS: The prevalence of recent immigrants (< or = 10 yrs)
      being PA (> or = 3 kkd) by ethnicity was: White (21%), Other (19%), Black (19%),
      Latin American (17%), West Asian/Arab (16%), East/Southeast Asian (14%), South
      Asian (11%). Recent immigrant Black men and White women had the highest
      prevalence of being PA (M = 27%, F = 18%) while South Asian men and women had the
      lowest prevalence (M = 14%, F = 9%). There is a gradient in the prevalence of
      being PA with recent immigrants (16%) < immigrants (20%) < non-immigrants (24%).
      Ethnic differences in the prevalence of being PA by time since immigration show
      similar patterns for men and women. Controlling for age, income, education and
      BMI had only small effects on the odds of being physical active across
      ethnicities and immigrant status. CONCLUSION: These results suggest that physical
      activity levels vary according to immigrant status and self-ascribed ethnicity in
      Canadian adults. Strategies to promote physical activity and prevent physical
      inactivity should consider both ethnicity and time since immigration.

PMID- 16967746
TI  - Drugs and driving: when science and policy don't mix.
AB  - This commentary briefly looks at the Canadian federal government's proposed
      legislation to strengthen the enforcement of drug-impaired driving, placing
      special emphasis on cannabis. After outlining the legislation, three issues are
      examined. Of primary concern is at what level cannabis use impairs driving
      ability leading to an increased risk of motor vehicle collision. Current
      epidemiological evidence is reviewed. Equally important is the government's
      emphasis on the training and implementation of Drug Recognition Experts (DREs),
      specially trained police officers whose role is to detect drivers under the
      influence of drugs. Research on the effectiveness of DREs is discussed, along
      with a dialogue regarding the potential shortcomings of the DRE program. Finally,
      a brief surveillance of international policy literature on drugs and driving is
      offered, along with some sober thoughts on the potential difficulties that may
      emerge in the enforcement of the proposed legislation.

PMID- 16967747
TI  - Vegetable and fruit food frequency questionnaire serves as a proxy for quantified
      intake.
AB  - BACKGROUND: Public health practitioners need valid tools to survey trends in
      dietary intake. The Rapid Risk Factor Surveillance System (RRFSS) includes an
      optional six-item vegetable and fruit intake food frequency questionnaire (FFQ)
      module. Our objectives were 1) to compare reported vegetable and fruit
      consumption from the FFQ to quantified servings (portions) defined by Canada's
      Food Guide to Healthy Eating and ascertained by a reference method, and 2) to
      compare the FFQ with the reference method for their classification of the
      proportion of respondents consuming five or more servings of vegetables and fruit
      per day. METHODS: Dietitians administered 24-hour recalls to each of 174 adult
      respondents who had completed the FFQ as part of the RRFSS. Recalls were
      conducted over the telephone on three separate occasions using an adaptation of
      the multiple pass method. RESULTS: The mean total intake of vegetables and fruit
      for the group was 4.6 times/day from the FFQ versus 4.8 servings/day from the
      recalls (paired t-test; p = 0.92). Thirty-seven percent of respondents were
      classified as consuming five or more times/day by the FFQ versus 35% by the 24
      hour recall servings. CONCLUSION: The FFQ tool can be used as a proxy for
      quantified intake of vegetable and fruit consumption.

PMID- 16967748
TI  - Research as intervention in heart health promotion.
AB  - BACKGROUND: Capacity building in health promotion has traditionally involved
      training interventions to support knowledge, skill and resource building for
      effective practice. However, there is a need to understand how research can be
      used to support capacity building and practice. METHODS: Findings are based on a
      parallel case study comprising qualitative analysis of 66 key informant
      interviews from five provincial heart health projects (Manitoba, Prince Edward
      Island, Ontario, Saskatchewan, and Newfoundland and Labrador) as part of the
      Canadian Heart Health Dissemination Project. FINDINGS: Results indicate research
      was used primarily to monitor and report results about health promotion capacity
      and dissemination to stakeholders, and contribute to participatory processes.
      Respondents noted that research as intervention had an influence on five areas of
      health promotion capacity and practice: increased heart health promotion
      knowledge/skills; improved programming, planning and prioritizing; increased
      motivation for (heart) health promotion initiatives; and cultivation of
      relationships as well as buy-in. INTERPRETATION: Research was a complementary
      capacity-building activity, although it did not directly increase program
      implementation. These findings contribute to linking researchers, practitioners
      and community decision-makers in the process of enhancing health promotion
      practice.

PMID- 16967749
TI  - Guiding health promotion efforts with urban Inuit: a community-specific
      perspective on health information sources and dissemination strategies.
AB  - OBJECTIVE: To develop a community-specific perspective of health information
      sources and dissemination strategies of urban Inuit to better guide health
      promotion efforts. METHODS: Through a collaborative partnership with the
      Tungasuvvingat Inuit Family Resource Centre, a series of key informant interviews
      and focus groups were conducted to gather information on specific sources of
      health information, strategies of health information dissemination, and overall
      themes in health information processes. FINDINGS: Distinct patterns of health
      information sources and dissemination strategies emerged from the data. Major
      themes included: the importance of visual learning, community Elders, and
      cultural interpreters; community cohesion; and the Inuit and non-Inuit
      distinction. The core sources of health information are family members and
      sources from within the Inuit community. The principal dissemination strategy for
      health information was direct communication, either through one-on-one
      interactions or in groups. CONCLUSION: This community-specific perspective of
      health information sources and dissemination strategies shows substantial
      differences from current mainstream models of health promotion and knowledge
      translation. Health promotion efforts need to acknowledge the distinct health
      information processes of this community, and should strive to integrate existing
      health information sources and strategies of dissemination with those of the
      community.

PMID- 16967750
TI  - Fire-related deaths among Aboriginal people in British Columbia, 1991-2001.
AB  - BACKGROUND: Fire-related mortality rates are known to be higher in Aboriginal
      people in BC. The purpose of this study was to describe the epidemiology and
      context of fire-related deaths in this population. METHODS: All death
      registrations attributable to fires in the province were identified by the B.C.
      Vital Statistics Agency (1991-2001). Age-specific death rates (ASDR) and age
      standardized mortality rates (ASMR) were calculated for Status Indians and other
      residents. Data from Coroner's reports from the B.C. Coroners' Service (1997
      2001) were used to describe the context of Aboriginal fire-related deaths.
      RESULTS: The overall fire-related ASMR for Status Indians and other residents
      were 0.66 deaths and 0.07 deaths/10,000 population respectively. Annual ASMR for
      both populations were constant over the study period. ASDR were higher in every
      age category for Status Indians; children and seniors had higher rates in both
      populations. Twenty-seven Aboriginal fatalities (20 fires) were identified for
      the contextual analysis. Key findings were: 48% of the total sample had elevated
      blood alcohol levels; 30% of the fires were caused by lit cigarettes (majority of
      decedents were intoxicated); 15% of the fires were caused by electric heating
      sources; at least 34% of fires occurred in homes with absent or non-functional
      smoke alarms. INTERPRETATION: Fire-related mortality among Aboriginal people in
      BC is a preventable public health concern. In this population, fire safety and
      prevention programs should consider improving the prevalence of functioning smoke
      alarms, promoting the safe use of heat sources, and decreasing smoking behaviours
      and the use of alcohol.

PMID- 16967751
TI  - Aboriginal participation in the DOVE study.
AB  - OBJECTIVE/BACKGROUND: Aboriginals constitute a substantial portion of the
      population of Northern Alberta. Determinants such as poverty and education can
      compound health-care accessibility barriers experienced by Aboriginals compared
      to non-Aboriginals. A diabetes care enhancement study involved the collection of
      baseline and follow-up data on Aboriginal and non-Aboriginal patients with known
      type 2 diabetes in two rural communities in Northern Alberta. Analyses were
      conducted to determine any demographic or clinical differences existing between
      Aboriginals and non-Aboriginals. METHODS: 394 diabetes patients were recruited
      from the Peace and Keeweetinok Lakes health regions. 354 self-reported whether or
      not they were Aboriginal; a total of 94 self-reported being Aboriginal. Baseline
      and follow-up data were collected through interviews, standardized physical
      assessments, laboratory testing and self-reporting questionnaires (RAND-12 and
      HUI3). RESULTS: Aboriginals were younger, with longer duration of diabetes, more
      likely to be female, and less likely to have completed high school. At baseline,
      self-reported health status was uniformly worse, but the differences disappeared
      with adjustments for sociodemographic confounders, except for perceived mental
      health status. Aboriginals considered their mental health status to be worse than
      non-Aboriginals at baseline. Some aspects of health utilization were also
      different. DISCUSSION: While demographics were different and some utilization
      differences existed, overall this analysis demonstrates that "Aboriginality" does
      not contribute to diabetes outcomes when adjusted for appropriate variables.

PMID- 16967752
TI  - What are the effects of tobacco policies on vulnerable populations? A better
      practices review.
AB  - BACKGROUND: While comprehensive tobacco policies have reduced the prevalence of
      smoking in Canada, some groups remain vulnerable to tobacco use and display high
      rates of smoking. This article reviews three types of tobacco policies--tax and
      price, smoking location restrictions and sales restrictions--and examines the
      consequences for Aboriginal people, youth and low-income people. METHODS: A
      better practices review model was used to assess the strength of studies
      published between 1990 and 2004 that examined the effects of these tobacco
      policies on the three vulnerable populations of interest. A total of 72 studies
      were assessed and 42 judged medium or high strength. A gender-based and diversity
      analysis was applied to assess the differential impacts on females and males
      and/or diverse characteristics within these populations. Intended and unintended
      consequences were examined. FINDINGS: Few studies assessed the potential or
      differential effects of tobacco policies on the three selected populations. In
      these, it was difficult to disentangle the effects of each policy in a
      comprehensive tobacco control environment, and there is need for improved
      indicators and greater attention to sex and gender analysis. CONCLUSIONS:
      Research is required to measure the intended and unintended impacts of tobacco
      policies on populations vulnerable to tobacco use. There are problems in
      assessing these studies that could be resolved with more precise indicator
      development. An equity-based framework for assessing the effects of tobacco
      policies is needed that is conceptually linked to health determinants and
      inequities. The article concludes with a set of recommendations for research,
      evaluation, policy and ethics arising from this review.

PMID- 16967753
TI  - Are the recommended taxonomies for the stages of youth smoking onset consistent
      with youth's perceptions of their smoking status?
AB  - BACKGROUND: To examine if the recommended taxonomies for the stages of youth
      smoking onset are aligned with the beliefs of smoking youth. METHODS: The SHAPES
      Tobacco Module was administered to 23,047 students (grades 9 to 13) in a
      convenience sample of 29 secondary schools during the 2000-2001 school year in
      the province of Ontario, Canada. Cross-tabs were used to compare a student's self
      perceived smoking status to their smoking status as determined with the currently
      recommended stage taxonomies for smoking behaviour. RESULTS: The majority of
      students classified as regular smokers (52.4%) and experimental smokers (98.9%)
      did not actually consider themselves to be smokers. Self-reported smoking status
      appeared to be relatively consistent for the never smoker and established smoker
      categories. CONCLUSIONS: Additional research is required to develop stage
      taxonomies that are aligned with the self-perceptions of non-established youth
      smokers.

PMID- 16967754
TI  - Methamphetamine use among marginalized youth in British Columbia.
AB  - BACKGROUND: Crystal methamphetamine (MA) is a powerful, highly addictive central
      nervous stimulant that can cause serious health consequences including
      neurotoxicity, paranoia, psychosis, depression, violence, and death. The
      objective of this study is to assess the prevalence and characteristics of MA use
      among two marginalized populations of youth (less than 30 years of age) in
      British Columbia. METHODS: A self-administered questionnaire was administered to
      a convenience sample of Vancouver street-involved youth (SY) and
      Lesbian/Gay/Bisexual/Transgender/Questioning (LGBTQ) centre youth in Vancouver
      and Victoria. Items measured include: participants' demographic characteristics;
      illicit substance use, including details of MA use; attempts at recovery and
      treatment; and potential consequences of MA use. RESULTS: One hundred and eighty
      of the 200 questionnaires distributed were completed. Sixty-seven percent of the
      SY and 24% of the LGBTQ youth reported ever having used MA. Of these: 43% had
      used within the last week; 46-57% used multiple times per day in their lifetime;
      they spent a maximum of 7-9 consecutive days awake; they began use in their
      middle to late teens; and half had sought help for a substance use disorder. SY
      who used MA within the last week were more likely to also use marijuana,
      cigarettes, heroin, ecstasy, and ketamine. Previous use of MA was associated with
      reports of auditory hallucinations. CONCLUSION: The current study demonstrates a
      high prevalence of MA use in two marginalized populations of youth. Use in sexual
      minorities, resulting psychopathology, and concurrent substance use all have
      important implications in delivery of service, prevention, and subsequent
      research.

PMID- 16967755
TI  - Prevalence and characteristics of body piercing and tattooing among high school
      students.
AB  - BACKGROUND: Although body piercing and tattooing seem to be gaining popularity
      among a diversity of social and age groups, studies of these practices in general
      adolescent populations are scarce. This study establishes the prevalence of body
      modification (tattooing and body piercing) among high school students in grades 7
      11 (aged 12 to 18). METHODS: Data come from a 2002 in-school survey conducted
      among a representative sample of 2,180 students (81% response rate) enrolled in
      the 23 high schools of the Outaouais region in Quebec. Systematic sampling was
      performed. Specific data on tattooing and body piercing are available for 2,145
      students (1% non-response rate). RESULTS: A prevalence of 27% for body piercing
      and 8% for tattooing is observed among high school students. Differences between
      girls and boys are observed in many ways: i.e., frequency and number of tattoos
      or piercings; aftercare practices. While most teens say that a "professional" in
      a studio performed their body modification and that they received aftercare
      instruction, a high percentage of students report health complications following
      the procedure. CONCLUSION: Results show that tattooing and body piercing are
      common among adolescents and may involve health risks. Consequently, appropriate
      preventive measures should be adopted by professionals such as school
      counsellors, nurses, physicians and others who are in contact with teenagers to
      help them make informed choices.

PMID- 16967756
TI  - What do women know about the risks of delayed childbearing?
AB  - BACKGROUND: Women aged 35 and older account for an increasing proportion of
      births and are at increased risk of pregnancy complications and poor infant
      outcomes. The objectives of the study were: 1) to determine what women know about
      delayed childbearing, including pregnancy complications and outcomes associated
      with low birthweight (LBW, < 2500 grams), preterm delivery (< 37 weeks) and
      multiple birth, and 2) to assess the characteristics of women with limited
      knowledge of risks. METHODS: A computer-assisted telephone interview survey was
      conducted with 1,044 randomly selected women who delivered their first live-born
      infant, between July 2002 and September 2003, in two urban centres, Calgary and
      Edmonton, in Alberta, Canada. RESULTS: The proportion of women aware of specific
      childbearing risks associated with advanced maternal age were as follows:
      conception difficulties (85.3%), multiple birth (24.0%), caesarean section
      (18.8%), preterm delivery (21.8%), and LBW (11.2%). Knowledge of specific
      developmental and health-related risks of suboptimal infant outcomes ranged
      between 18.0% and 46.5%. Logistic regression revealed that limited knowledge of
      maternal age-related pregnancy risks were associated with unplanned pregnancy
      (OR, 1.48; 95% CI, 1.03-2.14), smoking (OR, 1.83; 95% CI, 1.29-2.60) and non-use
      of fertility treatment (OR, 2.15; 95% CI, 1.44-3.19). Characteristics associated
      with limited knowledge of the risks associated with suboptimal birth outcomes
      were: age 35-39 years (OR, 2.98; 95% CI, 1.35-6.58), less than post-graduate
      education (< or = high school OR, 2.14; 95% CI, 1.20-3.82), and not currently
      enrolled as a student (OR, 1.75; 95% CI, 1.02-3.00). CONCLUSIONS: Many women are
      generally unaware of the potential consequences of delayed childbearing. There
      are missed opportunities in preconception counselling and education, which should
      be addressed to allow for more informed decision-making about family planning.

PMID- 16967758
TI  - The battle over your aching back.

PMID- 16967757
TI  - Predictors of influenza immunization among home care clients in Ontario.
AB  - BACKGROUND: This study examined factors associated with the receipt of influenza
      vaccination among Ontario home care clients. METHODS: Home care clients were
      assessed, as part of a routine home visit, during a pilot study of the Resident
      Assessment Instrument - Home Care (RAI-HC) in 12 Ontario Community Care Access
      Centres (CCACs). The RAI-HC is a multidimensional assessment that identifies
      clients' needs and level of functional ability. Multiple logistic regression was
      used to identify factors associated with influenza immunization in the two years
      prior to assessment. RESULTS: The overall rate of immunization reached about 80%
      by 2002. Factors such as age, respiratory problems, diabetes and congestive heart
      failure were associated with greater uptake, but overall rates of influenza
      immunization were lower than expected. Low education, smoking and poor medication
      adherence were negatively associated with influenza immunization. In addition,
      there was considerable variation in uptake among CCACs after adjusting for other
      significant individual-level independent variables. INTERPRETATION: Comprehensive
      assessments like the RAI-HC can be used to help identify and respond to health
      promotion and disease prevention issues in this population, and to compare rates
      across Canada.

PMID- 16967759
TI  - Folate deficiency results in alteration in intestinal brush border membrane
      composition and enzyme activities in weanling rats.
AB  - Folic acid deficiency is the most prevalent vitamin deficiency throughout the
      world and its effect on brush border membrane composition has not been studied
      earlier. We investigated the effect of folate deficiency on the structure and
      function of the intestinal brush border membrane. Various brush border enzyme
      activities, membrane sugars and lipids were evaluated in two groups of weanling
      male albino rats after 3 mo of feeding control and folate deficient diets. Except
      sucrase, all the other three enzymes, viz., alkaline phosphatase, leucine amino
      peptidase and y-glutamyl transpeptidase showed decrease in activity in rats fed
      folate-deficient diets. Among sugars, hexoses and hexosamines showed significant
      decline in amount whereas sialic acid content showed great increase in brush
      border membrane of folate-deficient rats as compared to controls. Furthermore,
      there was a significant reduction in cholesterol, phospholipids, triglycerides,
      cerebrosides and fucolipids in the group fed the folate-deficient diet. Our study
      suggests that folate deficiency results in altered enzyme activities, lipid and
      sugar composition of intestinal brush border membrane. Such changes might reflect
      the underlying cause of the gastrointestinal disturbances observed in folate
      deficiency.

PMID- 16967760
TI  - Abnormal increase in the expression level of proliferating cell nuclear antigen
      (PCNA) in the liver and hepatic injury in rats with dietary cobalamin deficiency.
AB  - Dietary cobalamin (Cbl; vitamin B12) deficiency resulted in severe growth
      retardation in rats, and body weight in the Cbl-deficient rats at 20 wk of age
      was significantly lower compared with the age-matched Cbl-sufficient control
      rats. In contrast, liver weight, when normalized to body weight, was greater in
      the Cbl-deficient rats than in the controls (p<0.05). The expression level of
      proliferating cell nuclear antigen (PCNA), a marker for cell proliferation, in
      the liver was significantly enhanced in the deficient rats, suggesting that cell
      proliferation is abnormally activated in the liver under Cbl-deficient
      conditions. In addition, plasma alanine aminotransferase (ALT) activity, a marker
      for hepatic injury, was also significantly elevated in the deficient rats. When L
      carnitine, which is used clinically for the treatment of Cbl-deficient patients
      with methylmalonic aciduria, was administered to the Cbl-deficient rats by
      intraperitoneal injection twice per day for 2 wk (each 0.5 mmol), the amount of
      methylmalonic acid excreted into the urine was significantly reduced, and the
      plasma ALT activity was lowered to a normal level. However, the PCNA expression
      in the liver was barely influenced by the treatment with carnitine. In contrast,
      when the deficient rats were fed an L-methionine-supplemented diet (4 g of L
      methionine per kg of the diet) for 2 wk, the increased expression of PCNA was
      normalized.

PMID- 16967761
TI  - Effects of genistein, an isoflavone, on pregnancy outcome and organ weights of
      pregnant and lactating rats and development of their suckling pups.
AB  - There is a general agreement that isoflavones can be beneficial to health in
      adults. However, isoflavones are well known as endocrine-disrupting chemicals. It
      should be considered that soy foods might adversely affect the reproductive
      system and infants. The aim of this study was to evaluate the effects of
      genistein, an isoflavone, on dams and their offspring. Maternal rats were fed
      diets containing genistein at levels of 0 and 0.5 g/kg diet from pregnancy day 5
      to postnatal day 13. No effects of genistein on the delivery, anogenital
      distance, reproductive organ weight, and body weight of the infants at birth were
      observed. There were no consistent effects on suckling pups after continuous
      genistein exposure during their fetal and suckling stages through their mothers,
      and there was no difference in effects according to the periods of exposure
      during pregnancy and lactation. We also observed no significant effect on the
      growth of offspring after weaning. Moreover, while we observed that the serum
      concentration of triiodothyronine (T3) in dams decreased, the result was a
      tendency, not a significant decrease. Our study suggested that maternal ingestion
      of genistein might have not induced serious adverse effects on dams, fetuses,
      infants or offspring during growth. However, the results indicated in many papers
      suggest the necessity of further study on the safety of genistein.

PMID- 16967762
TI  - Beef extract supplementation increases leg muscle mass and modifies skeletal
      muscle fiber types in rats.
AB  - The objective of this research was to investigate the effects of beef extract on
      fat metabolism, muscle mass and muscle fiber types in rats. We also investigated
      the synergetic effect of endurance exercise. Twenty-four male rats weighing about
      270 g were assigned to two diets containing 0 or 6% beef extract (BE). Half the
      rats fed each diet were subjected to compulsory exercise (CE) for 30 min every
      other day. After 4 weeks feeding, the blood was collected and various organs were
      dissected. The muscle fiber type of the soleus and extensor digitorum longus
      (EDL) muscles were evaluated by histochemical and electrophoretical analyses.
      Rats supplemented with BE showed a decrease in fat content in liver and abdomen
      and an increase in the activity of carnitine palmitoyl transferase II in liver.
      BE as well as exercise increased the relative weights of both soleus and EDL. BE
      alone and BE plus CE did not affect the distribution of muscle fiber types in
      soleus. BE without exercise decreased in type IIb of EDL from 54% to 44% with
      compensatory increase in type IIa from 41% to 49% and type I from 5% to 7%
      compared with the nonsupplemented, nonexercised control group. No synergetic
      effect on a fast to slow fiber conversion due to the combination of BE and CE was
      detected. Thus, BE supplement increased muscle mass and slow type fiber in EDL.
      The effects of BE supplement on muscle characteristics were similar to those of
      exercise. beef extract, fat metabolism, muscle fiber type, muscle mass, L
      carnitine

PMID- 16967763
TI  - Effects of chronic betaine ingestion on methionine-loading induced plasma
      homocysteine elevation in rats.
AB  - The effects of chronic betaine ingestion were investigated in rats. Rats were fed
      an experimental diet containing 5% betaine for 4 wk and methionine was
      intravenously administered. The elevations of plasma homocysteine were assessed
      by comparing the increments to the initial measured value and the positive
      incremental area under the plasma homocysteine concentration curve over the 240
      min post-methionine-loading period (deltaAUC0-240). In the betaine-ingesting
      rats, deltaAUC0-240 was significantly lower than in the control group (48% of the
      control), and the increments of plasma homocysteine were also lower compared with
      the control, especially 15-30 min after methionine loading. Choline, a precursor
      of betaine, did not alter the plasma homocysteine elevation. In a definite period
      immediately after methionine loading, carnitine, a methyl-group-rich amino acid,
      induced a significant increase of plasma homocysteine, compared to the control.
      Moreover, plasma homocysteine concentration was significantly decreased by 4 wk
      of betaine ingestion. Betaine enhanced liver BHMT activity whereas choline and
      carnitine did not show any effects on BHMT activity. These results suggest that
      betaine contributes to both the decrease in the plasma homocysteine concentration
      and the suppression of plasma homocysteine elevation through the activation of
      liver BHMT.

PMID- 16967764
TI  - Recovery and maintenance of copper levels in geriatric patients on enteral
      feeding for a prolonged period.
AB  - Latent copper deficiency develops after 3 mo in patients receiving enteral
      feeding solutions with low copper levels. We examined whether a copper-rich
      enteral solution restores and maintains the level of copper in serum for a
      prolonged period. The study group consisted of 13 patients (eight males and five
      females). Commercial preparations, F2alpha and Lifelon-PZ, for enteral
      administration were used. F2alpha and Lifelon-PZ contain 1.6 and 0.13 mg/L,
      respectively, of copper. Serum copper levels were monitored in patients before
      and after administration of F2alpha, a copper-rich enteral solution, at the
      neurological ward of Nagoya Daini Red Cross Hospital. Four of the 13 patients
      received Liflon-PZ, a copper-poor enteral solution, before this trial. Blood
      samples were taken every month. The daily average copper dosage with F2alpha was
      1.8 +/- 0.4 mg/d (1.0-2.4 mg/d). The copper level in the four patients who
      received Liflon-PZ was 10.5 +/- 5.5 micromol/L before this trial. The level rose
      to 18.9 +/- 3.6)mol/L 1 mo after the change to the copper-rich, F2alpha. The
      average serum copper level in the other patients before the start of enteral
      feeding was 15.3 +/- 5.0 micromol/L. The proper copper level was maintained with
      F2alpha in the long term. A copper-rich enteral preparation could easily restore
      and maintain serum copper levels for a prolonged period. A dose of 1.8 +/- 0.4 mg
      copper/d (1.0-2.4 mg/d) was sufficient for our patients.

PMID- 16967765
TI  - Association of dietary fiber with temporal changes in serum cholesterol in
      Japanese-Brazilians.
AB  - To examine dietary intakes in relation to long-term serum lipoprotein changes in
      a prospective cohort study with 7 y of follow-up, serum lipids were analyzed by
      enzymatic methods, while food intake was calculated from validated food frequency
      questionnaires. First- and second-generation Japanese-Brazilians (n = 316) living
      in Bauru, Sao Paulo/Brazil, of both genders, aged 40 to 79 y were assessed at
      baseline in 1993. Multiple linear regression models were used with changes in
      serum lipoproteins as the dependent variable and changes in dietary intakes as
      the independent variables, adjusted for confounding factors. In energy-adjusted
      analyses, changes in serum total cholesterol were inversely associated with
      changes in total dietary fiber, fruits/fruit juices and vegetables after
      adjustment for age and gender. Each increase of 10 g in the consumption of total
      dietary fiber was associated with a reduction of 12.5 mg/dL in the serum total
      cholesterol (p<0.05). Our results highlight the importance of increased intakes
      of total fiber, fruits and vegetables to prevent and control dyslipidemia in
      Japanese migrants.

PMID- 16967766
TI  - Effects of ingestion of collagen peptide on collagen fibrils and
      glycosaminoglycans in the dermis.
AB  - In order to investigate the effects of collagen peptide ingestion on fibroblasts
      and the extracellular matrix in the dermis, collagen peptide was administered
      orally to pigs at 0.2 g/kg body weight/d for 62 d, and its effects were compared
      with those of lactalbumin and water controls. Fibroblast density, and diameter
      and density of collagen fibrils were significantly larger in the collagen peptide
      group than in the lactalbumin and water control groups. The two major components
      of dermal glycosaminoglycans, hyaluronic acid and dermatan sulfate, which are
      present in the inter-fibrillar space, did not differ significantly among the
      three groups. However, the ratio of dermatan sulfate, which is derived from
      fibril-bound decorin, was largest in the collagen peptide group. These results
      suggest that ingestion of collagen peptide induces increased fibroblast density
      and enhances formation of collagen fibrils in the dermis in a protein-specific
      manner.

PMID- 16967767
TI  - Chemical components, palatability, antioxidant activity and antimutagenicity of
      oncom miso using a mixture of fermented soybeans and okara with Neurospora
      intermedia.
AB  - The enzyme activities of Aspergillus oryzae on koji (malted rice) and Neurospora
      intermedia on S-oncom and O-oncom (fermented soybeans and okara with N.
      intermedia, respectively) were compared. The major enzymes of N. intermedia were
      different from those of A. oryzae, and the enzyme activities of O-oncom were
      extremely higher than those of S-oncom. S5-Miso, S10-miso and S9O1-miso replacing
      50% or 100% of steamed soybeans with S-oncom or a 9 : 1 mixture of S-oncom and O
      oncom, respectively, were prepared to supplement the enzyme action of koji. The
      chemical components of those miso were almost the same as those of soybean-miso
      (C-miso). The miso soups prepared with S5-miso, S10-miso and S9O1-miso were all
      considered to be more palatable and pleasant-tasting than the soup prepared with
      C-miso, and their flavor was preferred in the same degree as that of T5-miso
      using 50% tempeh, the soybeans fermented with Rhizopus oligosporus. Scavenging
      activities of DPPH and O2- and antimutagenicity of the 70% ethanol extract from
      those miso were higher than those of hot-water extract, and the activities of
      S9O1-miso were the highest. The isoflavone-aglycons and brownish color of S9O1
      miso were higher than those of C-miso. The higher contents of isoflavone-aglycons
      and melanoidines of S9O1-miso might contribute to their higher antioxidant
      activity and antimutagenicity. From these results, S9O1-miso has potential as a
      healthier alternative to C-miso in terms of taste and health benefits.

PMID- 16967768
TI  - Suppression of apolipoprotein B secretion from HepG2 cells by glucosyl
      hesperidin.
AB  - Our previous study has shown that a soluble hesperidin derivative, glucosyl
      hesperidin (G-hesperidin), preferentially lowers serum triglyceride (TG) level in
      hypertriglyceridemic subjects through the improvement of very low-density
      lipoprotein (VLDL) metabolic abnormality. G-Hesperidin has also been found to
      decrease an elevated serum apolipoprotein B (apo B) level in the
      hypertriglyceridemic subjects, suggesting a possibility that this compound
      suppresses excess VLDL secretion in the liver. In the present study, to gain a
      better understanding of possible mechanisms by which G-hesperidin lowers serum
      TG, we examined whether this derivative affects apo B secretion from HepG2 human
      hepatoma cells, a model of hepatic VLDL secretion. As a result, G-hesperidin
      significantly reduced apo B secretion from the oleate-stimulated HepG2 cells.
      Furthermore, G-hesperidin significantly suppressed apo B secretion only in the
      oleate-stimulated cells and failed to act on the cells incubated without oleate.
      In the oleate-stimulated cells, G-hesperidin significantly decreased cellular
      cholesteryl ester (CE), although it had no effect on cellular TG or free
      cholesterol amounts. Moreover, the oleate-stimulated cells had a decrease in
      cellular apo B amounts by G-hesperidin exposure. These findings indicate that G
      hesperidin down-regulates the assembly of apo B-containing lipoproteins via the
      reduction of CE synthesis augmented with oleate and results in suppressing excess
      apo B secretion from the cells. This effect is speculated to be associated with
      the improvement of VLDL metabolic abnormality in hypertriglyceridemic subjects
      and considered as a mechanism of lowering serum TG.

PMID- 16967769
TI  - Decompression sickness following breath-hold diving.
AB  - Despite convincing evidence of a relationship between breath-hold diving and
      decompression sickness (DCS), the causal connection is only slowly being
      accepted. Only the more recent textbooks have acknowledged the risks of
      repetitive breath-hold diving. We compare four groups of breath-hold divers: (1)
      Japanese and Korean amas and other divers from the Pacific area, (2) instructors
      at naval training facilities, (3) spear fishers, and (4) free-dive athletes.
      While the number of amas is likely decreasing, and Scandinavian Navy training
      facilities recorded only a few accidents, the number of spear fishers suffering
      accidents is on the rise, in particular during championships or using scooters.
      Finally, national and international associations (e.g., International Association
      of Free Drives [IAFD] or Association Internationale pour Le Developpment De
      L'Apnee [AIDA]) promote free-diving championships including deep diving
      categories such as constant weight, variable weight, and no limit. A number of
      free-diving athletes, training for or participating in competitions, are
      increasingly accident prone as the world record is presently set at a depth of
      171 m. This review presents data found after searching Medline and ISI Web of
      Science and using appropriate Internet search engines (e.g., Google). We report
      some 90 cases in which DCS occurred after repetitive breath-hold dives. Even
      today, the risk of suffering from DCS after repetitive breath-hold diving is
      often not acknowledged. We strongly suggest that breath-hold divers and their
      advisors and physicians be made aware of the possibility of DCS and of the
      appropriate therapeutic measures to be taken when DCS is suspected. Because the
      risk of suffering from DCS increases depending on depth, bottom time, rate of
      ascent, and duration of surface intervals, some approaches to assess the risks
      are presented. Regrettably, none of these approaches is widely accepted. We
      propose therefore the development of easily manageable algorithms for the
      prevention of those avoidable accidents.

PMID- 16967770
TI  - Perceived exertion is related to muscle activity during leg extension exercise.
AB  - This study examined the relationship between ratings of perceived exertion and
      muscle activity during dynamic leg extension exercise using a resistance exercise
      specific OMNI-RPE scale. Twenty volunteers (10 males, 10 females, age 22.2 +/-
      3.1 yr) performed one set of leg extension exercise at 30%, 60%, and 90% of their
      one-repetition maximum (1-RM). OMNI-RPE responses were assessed for both the
      active muscle (OMNI-AM) and the overall body (OMNI-O) following each intensity.
      Electromyography (EMG) data were collected from the rectus femoris, vastus
      lateralis, and vastus medialis muscles. A two-factor repeated measures ANOVA
      showed a significant OMNI-RPE (region) X intensity interaction (p < 0.01). Both
      OMNI-AM and OMNI-O increased with exercise intensity, and RPE-AM was higher than
      RPE-O at all intensities. EMG activity increased with exercise intensity in all
      muscle groups (all p < 0.01). Muscle activity was significantly and positively
      related to OMNI-RPE in both the active muscle and overall body (all p < 0.01).
      The OMNI-Res RPE scale may be a promising technique for regulating resistance
      training intensity.

PMID- 16967771
TI  - Changes in blood markers of serotoninergic activity following high intensity
      cycle ergometer exercise.
AB  - The purpose of this study was to measure concentrations of adrenaline (A),
      noradrenaline (NE), free tryptophan (f-Trp), prolactin (PRL), nonesterified fatty
      acids (NEFA), and blood lactate following 30 s of high-intensity cycle ergometer
      exercise. Adrenaline (A) and NE concentrations increased immediately postexercise
      (P < 0.05) and returned to levels observed at baseline 24 h later. Plasma f-Trp
      concentration decreased by 23.5% immediately following exercise (P < 0.05). There
      were no changes observed in serum concentrations of PRL. Plasma NEFA
      concentrations decreased immediately following exercise by 46% (P < 0.05) and
      returned to baseline values 24 h later. Whole blood lactate concentrations
      increased immediately post exercise (P < 0.05), and were higher than those
      measured 24 h later (P < 0.05). These findings indicate that blood markers of
      serotoninergic activity were unaltered by a single 30 s bout of maximal cycling.

PMID- 16967772
TI  - Strength and speed characteristics of elite, subelite, and recreational young
      soccer players.
AB  - The purpose of the present study was to compare maximal isometric force, force
      time curve characteristics, pedaling rate, vertical jump, and sprint performance
      among young soccer players from different competition levels. Fifty-four (54)
      young soccer players were divided into three groups according to competition
      level: the elite group (n=18) consisted of soccer players from the national youth
      soccer team of Greece, the subelite group (n=18) consisted of youth soccer
      players who participated in the local championship, and the recreational group
      (n=18) consisted of recreational soccer players. All groups were evaluated for
      maximal isometric force, explosive force at 100 msec, peak force relative to body
      mass, rate of force development, squat and drop jump heights, 10 m sprint time,
      and pedaling rate. The elite group presented significantly (p < 0.05) higher
      maximal isometric force, vertical jump height, and pedaling rate, and lower 10 m
      sprint time in comparison with the subelite and recreational groups. No
      significant differences were observed in strength and speed characteristics
      between the subelite and recreational young soccer players. The findings of the
      present study suggest that the elite young soccer players can be distinguished
      from subelite and recreational young soccer players in strength and speed
      characteristics. These strength and speed measures can be used for strength and
      speed diagnosis, and for designing and evaluating training programs.

PMID- 16967773
TI  - The effect of corrective taping of the patella on patella position as defined by
      MRI.
AB  - Taping of the patella is a common treatment for patellofemoral pain syndrome
      (PFPS) and has been shown to reduce pain. The reason for this affect is unknown;
      it has been proposed that taping alters patella orientation. Magnetic resonance
      imaging (MRI) studies investigating this are limited and the results are
      contradictory. Eight subjects (5 female, 3 male, 10 knees in total) with PFPS
      were involved in the study. MRI scans were taken at 0, 10, and 20 degrees of knee
      flexion, prior to and after patella taping. Lateral patella displacement (LPD)
      was determined for both conditions at each joint angle. Mean LPD data were
      compared using two-way ANOVA. Taping resulted in a significant reduction in LPD
      (p < 0.05) at all joint angles. The absolute average reductions in LPD here 0.4,
      1.1, and 0.7 mm at 0 degree, 10 degrees, 20 degrees knee flexion, respectively.
      This change was small but might be sufficient to bring about the biologically
      significant changes resulting in the reported reduction in pain.

PMID- 16967775
TI  - Chemotherapy using intra-arterial infusion for oral cancer.
AB  - There are three historically recognized methods of intra-arterial infusion for
      oral cancer: Conventional intra-arterial infusion via the superficial temporal
      artery: Superselective intra-arterial infusion via the femoral artery (Seldinger
      method), New superselective intra-arterial infusion via the superficial temporal
      artery. Here we report a recent instance of daily concurrent chemoradiotherapy
      using a new superselective intra-arterial infusion. A catheter with a curved tip
      was inserted superselectively into the feeding artery of the tumor via the
      superficial temporal artery (long-term catheterization has become possible using
      this method). The patient with T3 tongue cancer was treated by chemoradiotherapy.
      Radiotherapy (total dose: 40 Gy/4weeks) and superselective intra-arterial
      infusion chemotherapy using docetaxel (DOC) (total dose: 60 mg/m2/4weeks, 15
      mg/m2/week) and cisplatin (CDDP) (total dose: 100 mg/m2/4weeks, 5 mg/m2/day) were
      concurrently performed daily, followed by surgery, after which no major
      complication was observed. The clinical effect was complete response (CR), and
      the pathological effect on the resected tumor after surgery was pathological CR.
      This method promises to be a new strategy of choice for the treatment of oral
      cancer.

PMID- 16967774
TI  - Influence of carbohydrate on immune function following 2 h cycling.
AB  - The influence of carbohydrate compared with placebo ingestion on changes in
      immune cell counts and functions following 2 h intensive cycling was studied in
      12 trained cyclists who functioned as their own controls. The subjects performed
      two tests 2 weeks apart where they cycled for 2 h at approximately 64% Watts(max)
      while receiving 4 mL x kg(-1) x 15 min(-1) carbohydrate (6%) (Cho) or placebo
      (Pla) beverages. Blood samples were collected 30 min preexercise, and immediately
      and 1 h postexercise. The samples were assayed for plasma cortisol and
      epinephrine, blood leukocyte subset counts, PHA-induced lymphocyte proliferation,
      and natural killer cell activity (NKCA). Compared with Pla ingestion, Cho
      attenuated exercise-induced changes in plasma cortisol, blood neutrophil, and
      monocyte counts, but not in total blood lymphocyte, T cell, and NK cell counts,
      PHA-induced lymphocyte proliferation, and NKCA. Thus despite a strong attenuating
      influence of carbohydrate ingestion on exercise-induced changes in plasma
      cortisol and blood neutrophil and monocyte counts, other immune measures related
      to lymphocyte subset counts, and function were unaffected.

PMID- 16967776
TI  - Influence of age and sex on high-fat diet-induced increase in blood pressure.
AB  - We are studying to elucidate the reason for increase in age-related hypertension
      and the mechanism thereof using rats. We would like to introduce model animals
      and the results obtained from these animal experiments. Based on a study
      regarding whether the elevation of blood pressure caused by dietary fat is due to
      excessive calorie intake and resulting body-weight gain or else fat itself--if so
      which type of fat is responsible for elevating blood pressure, it was suggested
      that elevated blood pressure was due to some effects specific to animal fat.
      According to a study if insulin resistance involves elevated blood pressure, it
      became apparent that the build-up of visceral fat caused by high-fat diet
      together with worsening of insulin sensitivity were responsible for elevating
      blood pressure. Next, we studied if there are sexual differences in dietary-fat
      induced hypertension and influence of male hormone. It became clear that the
      mechanism of elevated blood pressure caused by high-fat diet involved a condition
      of insulin resistance due to high-fat diet and furthermore, only when
      testosterone was present, the blood pressure was elevated. In addition, we
      studied aging effects on hypertension due to dietary fat. As a result, it became
      clear that the older the person gets, more likely he/she suffers from visceral
      obesity and conditions of insulin resistance, making blood pressure proneto rise.
      In summary, even without having excessively high calorie diet and without body
      weight gain, intake of excessive animal fat will cause visceral obesity and so do
      hypertension. Also, when taking high-fat diet, males tend to suffer from
      hypertension more often than females, suggesting testosterone is involved as the
      cause. Further, it was shown that the older the persons are, the greater the
      dietary effects result in, causing their blood pressures likely to increase.

PMID- 16967777
TI  - Influence of monitor luminance and room illumination on soft-copy reading
      evaluation with electronically generated contrast-detail phantom: comparison of
      cathode-ray tube monitor with liquid crystal display.
AB  - The influence of monitor brightness and room illumination on soft-copy diagnosis
      by both cathode-ray tube (CRT) monitor and liquid crystal display (LCD) was
      evaluated and compared using a contrast-detail phantom. Nine observers (7
      radiologists and 2 radiological technicians) interpreted six types of
      electronically generated contrast-detail phantom images using a 21-inch CRT
      (2,048x2,560) and a 21-inch LCD (2,048x2,560) under 6 kinds of viewing
      conditions, i.e. monitor brightness of 330 cd/m2 or 450 cd/m2, and room
      illumination of 20, 100 or 420 lux at the center of the display. Observers were
      requested to determine the visible borderline of the objects. Between 330 cd/m2
      and 450 cd/m2, no significant difference in the visible area was found under any
      of the three lighting conditions. However, in two low-contrast phantom images,
      the visible area on the LCD was significantly larger than that on the CRT,
      independent of both monitor brightness and room illumination. (p<0.05). The
      effect of room illumination was not significant, suggesting that the use of LCD
      at high room illumination is acceptable.

PMID- 16967778
TI  - Factors related to frequency of engaging in outside activities among elderly
      persons living an independent life at home.
AB  - We examined by cross-sectional design the association between the frequency of
      outside activity and the demographic, health problem, lifestyle, psychosocial and
      environmental factors among 239 community-dwelling elderly Japanese people (105
      men and 134 women) aged 65 years and older, who lived independently at home. The
      associations of the outside activities more than 6-7 days per week based on a
      categorical questionnaire choice with potential factors were expressed by odds
      ratio (OR) and 95% confidence interval (CI) calculated through logistic
      regression analysis by sex. The proportions of those engaging in outside activity
      more than 6-7 days per week were 38.1% and 21.6% among men and women,
      respectively. The associations of the factors belonging to various fields with
      the frequency of engaging in outside activities were clearly pronounced among
      men. Elderly men engaging in outside activities more often were scored less for
      depression and more socially active than men engaging in outside activities less
      often. Multiple regression analysis revealed meeting and talking often with
      friend (OR=4.18, 95% CI: 1.06-16.5), current alcohol consumption (3.01, 1.06
      8.54), having any hobby (3.59, 0.94-13.7), and easy access to public
      transportation (3.43, 1.28-9.16) as significant or borderline significant factors
      related to engaging in outside activities more than 6-7 days per week. Women who
      were currently employed engaged in outside activities more frequently. The
      frequency of engaging in outside activities was associated with factors belonging
      to various fields among elderly people living independently, particularly among
      men, suggesting its usefulness as an indicator of comprehensive well-being.

PMID- 16967779
TI  - Evaluation of new image processing conditions for digital mammograms from Fuji
      computed radiography.
AB  - PURPOSE: A new processing parameter (T-type parameter) setting for gray scale was
      developed to improve the image quality of digital mammograms. To clarify the
      usefulness of this parameter setting, we have evaluated the image quality of
      digital mammograms (hard copy images) processed with this parameter, and compared
      it with S/F mammography. MATERIAL AND METHODS: Mammograms were made under the
      same radiographic conditions by the S/F and FCR systems (type 1, S/F; type 2 and
      3, FCR with new T-type parameters; type 4 and 5, FCR with conventional
      parameters). A total of 49 images from 10 cases was selected for evaluation
      testing. Evaluation items were the contrast visibility of mammary glands and
      adipose tissues together with their granularity and sharpness. Eleven medical
      doctors participated in evaluating the images. RESULTS: The FCR hard copy images
      processed with the T-type parameter settings were significantly preferred over
      the conventional S/F images for the contrast visibility of mammary glands and
      adipose tissue. As for the other items (except for granularity), the FCR hard
      copy images processed with the T-type parameter settings were subjectively
      evaluated as slightly better than or equal to the S/F images. In contrast, the
      conventional S/F images were significantly preferred over the FCR hard copy
      images processed with the conventional parameter settings. CONCLUSION: The image
      quality of FCR hard copy images processed with the T-type parameter settings was
      preferred over that of conventional S/F images as evaluated by medical doctors
      who specialized in mammography interpretation.

PMID- 16967780
TI  - Application of subsecond rotation scan to helical CT for lung cancer screening.
AB  - PURPOSE: To clarify whether the benefit of a reduced effective scan width
      obtained using a smaller pitch outweighs the disadvantage of increased noise in
      the application of a subsecond helical CT to mass screenings for lung cancer.
      MATERIALS AND METHODS: Twenty-two helical CT scans of the lung were obtained in
      11 healthy subjects using the following parameters: 1) scan 1 was performed at
      120 kVp, 50 mA, 10-mm collimation, 1-second/rotation, helical pitch of 2.0; and
      2) scan 2 was performed at 120 kVp, 50 mA, 10-mm collimation, 0.75
      second/rotation, helical pitch of 1.5. Computer-generated nodules measuring 10 mm
      and 6 mm in diameter showing ground-glass opacity were superimposed on these
      images. The detectability of each nodule was evaluated by six blinded readers
      using ROC analysis. RESULTS: Detectability of the 6-mm nodules was significantly
      higher in scan 2 than in scan 1. Detectability of the 10-mm nodules was not
      significantly different between scans 1 and 2. CONCLUSION: The use of a smaller
      pitch by employing a subsecond rotation scan in a helical CT for lung cancer
      screenings improves the detection of small lesions without increasing either the
      scanning time or radiation dose.

PMID- 16967781
TI  - Intra- and interobserver agreement and performance score of breast phantom image
      interpretation: influence of ambient room lighting levels.
AB  - The influence of ambient room lighting conditions on soft-copy breast phantom
      image interpretation was evaluated by comparing cathode ray tube (CRT) monitors
      with liquid crystal displays (LCDs). Nine observers were asked to use a three
      point scale to rate the visibility of various phantom objects (masses, specks,
      and fibers) displayed on a 21-inch CRT (2,560 x 2,048) and a 21-inch LCD (2,560 x
      2,048) under three different levels of ambient lighting (20, 100 and 420 lux at
      the display center). Each phantom image was interpreted twice, and the
      reproducibility of judgment and inter-observer agreement was evaluated using
      kappa statistics. Except for the "mass" score, the LCD score showed a
      significantly higher value (p<0.05) compared with that of CRT. Nevertheless, no
      significant differences were found among the three lighting levels. Furthermore,
      intra- and inter-observer agreement in judgments showed no effects of room
      illumination. Although the breast phantom objects were better visualized on LCDs
      than on CRT monitors, room illumination did not affect the performance score of
      soft-copy reading.

PMID- 16967782
TI  - Impaired insulin-regulated membrane aminopeptidase translocation to the plasma
      membrane in adipocytes of Otsuka Long Evans Tokushima Fatty rats.
AB  - Insulin-regulated membrane aminopeptidase (IRAP) translocates to the plasma
      membrane with glucose transporter-4 (GLUT4) on insulin stimulation. However, this
      may be impaired in patients at risk of diabetes. Recently a novel technique has
      been developed to assess cell surface IRAP activity dynamically using a
      fluorogenic membrane impermeable substrate. In this study we measured the cell
      surface IRAP activity and 3-O-[methyl-14C]-D-Glucose uptake in adipocytes
      isolated from Otsuka Long Evans Tokushima Fatty rats (OLETF), developed as a
      model of type 2 diabetes mellitus, to evaluate whether the translocation of
      GLUT4/IRAP vesicles is affected. On the addition of insulin, the cell surface
      IRAP activity promptly increased to reach equilibrium in a hormone dose-dependent
      manner. OLETF rats showed significantly lower equilibrium activity than control
      rats (P<0.01). Time to reach the equilibrium was also significantly longer in the
      OLETF case, and adipocytes isolated from OLETF rats demonstrated both a delay and
      a reduction in 3-O-[methyl-14C]-D-Glucose uptake. This impairment in all
      parameters was alleviated by treatment with pioglitazone. Continuous measurement
      of cell surface IRAP activity allowed accurate evaluations of GLUT4/IRAP vesicle
      translocation and of the establishment of defects in OLETF rats.

PMID- 16967783
TI  - Thinness: a woman's conflict or Eating Disorders: facts and the search for
      solutions.

PMID- 16967784
TI  - Identifying needs and barriers to diabetes education in patients with diabetes.
AB  - OBJECTIVE: To assess the needs, awareness and barriers to diabetes education for
      self management and to facilitate the initiation of an education programme
      promoting self care among diabetics and their families. METHODS: A qualitative
      study was conducted among adult diabetics attending outpatient clinics in a
      tertiary care teaching hospital in Karachi, Pakistan. Semi-structured interviews
      were conducted on 27 subjects (11 men; 16 women) to identify dominant themes and
      priority issues. RESULTS: Participants displayed great deal of variation with
      respect to level of knowledge and motivation for education. Most believed that
      diabetes was caused by stress. Family was perceived to be a source of positive
      support. Relative ease of adherence to pharmacological regimens as compared to
      diet and exercise was reported. Participants expressed frustration at chronicity
      of disease and fear of developing certain specific complications and inheritance
      by their children. Barriers to enhancing knowledge included 'No need for further
      information', distance from training institutions and other priorities.
      CONCLUSION: Knowledge, beliefs and fears about diabetes, family influence and
      accessibility of healthcare, affects management behaviours and learning.
      Understanding needs and expectations of people with diabetes is essential in
      initiating and improving the outcomes of education programme for diabetes self
      care.

PMID- 16967785
TI  - A randomized clinical trial comparing 50mCi and 100mCi of iodine-131 for ablation
      of differentiated thyroid cancers.
AB  - OBJECTIVE: To compare the efficacy of low (50 mCi) and high dose (100 mCi) Iodine
      131 in ablation of differentiated thyroid cancer remnants. METHODS: Baseline
      serum thyroglobulin (sTg), thyroglobulin antibody (Tg Ab) and diagnostic whole
      body iodine scan with 2 mCi of I-131 were performed in each individual. After 6
      months serum Tg, Tg Ab (of-thyroxin) and WB iodine scan with 10 mCi of I-131 were
      done to assess the efficacy of the low and high dose of I-131. Iodine ablative
      therapy (IAT) was considered successful (complete ablation) if the I-131 whole
      body scan was negative and sTg level was undetectable. In case of positive scan
      and/or sTg level detectable the patient was considered as
      unsuccessfully/partially ablated. RESULTS: In group A, (high dose) successful IAT
      was seen in 12/20 (60%) patients. Of these 5/7 (71%) had follicular Carcinoma on
      histopathology and 7/13 (54%) had papillary Ca. In group B, (low dose) successful
      IAT was seen in 8/20 (40%) patients, out of which 3/10 (30%) had follicular
      Carcinoma on histopathology and had successful IAT. 5/10 (50%) patients with
      papillary Carcinoma had successful IAT. As far as histopathology is concerned, in
      group A, response to high dose I-131 was better in follicular type than papillary
      type. Whereas in group B, response to low dose I-131 was better in patients with
      papillary type than follicular. CONCLUSION: 100 mCi of radioactive Iodine-131 (I
      131) is a more effective therapeutic dose than 50 mCi (I-131) in the treatment of
      differentiated thyroid cancer remnants. Furthermore, follicular Carcinoma respond
      better to 100 mCi I-131 than 50 mCi while papillary Carcinoma showed an almost
      equal response to both.

PMID- 16967786
TI  - Appropriate and inappropriate use of fresh frozen plasma.
AB  - OBJECTIVE: To analyze the current situation of use and misuse of fresh frozen
      plasma (FFP) in various clinical situations. METHODS: This was a cross sectional
      study done at Liaquat National Hospital (LNH) during a period of 4 months from
      December 2002 to March 2003. About 300 file records of those patients who
      received fresh frozen plasma were studied. Each file record was checked for the
      diagnosis of the patient, coagulation profile and doctor's trigger for blood
      transfusion. The indications of FFP were checked according to guidelines set by
      British Committee of Standards and Haematology. RESULTS: Of 1486 units of FFP
      that were transfused to 300 patients, it was observed that 78.6% (1169 / 1486) of
      FFP was appropriately transfused while the remaining 21.3% (317/1486 units) was
      used without any supportive evidence. CONCLUSION: Although majority of the plasma
      was used appropriately, a considerable volume of plasma was also wasted.

PMID- 16967787
TI  - The pattern of malignant tumours: tumour registry data analysis, AFIP,
      Rawalpindi, Pakistan (1992-2001).
AB  - OBJECTIVE: To provide information regarding frequency of malignant tumours
      through data retrieved from pathology based tumour registry of AFIP, Rawalpindi,
      Pakistan. METHODS: All malignant tumours recorded with the AFIP tumour registry
      over a period of 10 years (1992-2001) were analysed in terms of age group, gender
      and type of tumour with relation to site. A comparison with the previously
      published material from same setting, national and international studies were
      also done. RESULTS: The total malignant tumours in the 10 years period were
      21,168. Out of these, 12584 (59.5%) were seen in male patients while 8584 (40.5%)
      were in females. Total malignant tumours in pediatric age group were 927 (4.4%).
      The common malignant tumours in males in order of decreasing frequency were,
      those of prostate, skin, lymph node, leukaemia, urinary bladder, colorectum,
      bone, lung, stomach and liver. In females, breast carcinoma was on top followed
      by skin, leukaemia, ovary, coloretum, lymph node, bone, liver, cervix and gall
      bladder. In females, contrary to the Western studies and India, ovarian tumours
      were more frequent than cervical cancers. Comparison of this analysis with our
      previous analysis, national and international studies showed some interesting
      features. CONCLUSION: It was found that in males, tumours of the prostate were
      the most frequent as compared to the previous study, which showed lymphomas and
      leukemias to be the most common. On the other hand in females, tumours of the
      breast remained to be consistently most frequent.

PMID- 16967788
TI  - Surgical ligation of scrotal varicocele for male factor infertility is a valid
      option of treatment.
AB  - OBJECTIVE: To evaluate the role of surgical ligation of scrotal varicocele for
      treatment of male factor infertility. METHODS: We studied 60 patients who
      presented with infertility and were also found to have scrotal varicocele.
      Patients with other probable causes contributing to infertility were excluded.
      Diagnosis was made by clinical examination and scrotal ultrasonography. All the
      patients underwent either laparoscopic varicocelectomy or open retroperitoneal
      high ligation of the testicular veins. Operative time and hospital stay was
      recorded. All patients were evaluated for postoperative improvement of semen
      parameters and development of any postoperative complication. The results were
      analyzed by commercially available software. RESULTS: During the study period 5
      patients were lost to follow up and were excluded. The rest of patients (n=55)
      were young, with age ranging from 20-35 years (Mean age 27.8 years, SD +/- 4.38).
      All patients had unilateral left sided varicocele; two patients (3.6%) had grade
      I varicocele, 21 patients (38.2%) had grade II varicocele and 32 patients (58.2%)
      had grade III varicocele. Statistically significant improvement in sperm density
      (p value < 0.05), sperm activity (p value < 0.05) and sperm morphology (p value <
      0.05) was observed after the surgical ligation. The mean operative time was 54.88
      minutes (SD + 13). The mean hospital stay in laparoscopic procedure was 33.4 (SD
      + 15.3). Minor complications were noted in 13 patients and included superficial
      wound infection in 3 patients, 6 patients exhibited testicular pain and
      persistence of varicocele in 4 patients. CONCLUSION: Surgical ligation of scrotal
      varicocele is asafe and effective mode of treatment of male factor infertility in
      selected population.

PMID- 16967789
TI  - Comparison of the Personal Health Questionnaire and the Self Reporting
      Questionnaire in rural Pakistan.
AB  - OBJECTIVE: To apply ROC analysis to select the best threshold scores for the PHQ
      and SRQ; to compare the sensitivity and specificity of the PHQ and SRQ against a
      criterion diagnosis of depressive disorder in a community sample in rural
      Pakistan, and to examine the influence of socio-demographic factors on
      misclassification. METHODS: The study used a two-stage design. Receiver Operating
      Characteristic (ROC) analysis was used to estimate the optimal threshold score
      and to compare the ability of the Self Reporting Questionnaire (SRQ) and the
      Personal Health Questionnaire (PHQ) to discriminate between cases of depressive
      disorder and non-cases. RESULTS: The results of the ROC analysis suggest that the
      SRQ is superior to the PHQ, and at the threshold of 5/6, the SRQ has superior
      sensitivity, negative predictive value and percentage agreement compared with the
      PHQ. When the SRQ threshold is raised it gains specificity, and at a cut-off
      threshold of 7/8 it is superior to the PHQ (5/6) in all validity coefficients and
      percentage agreement. Only gender and the presence of a confidant had a
      significant effect on misclassification using the SRQ among the cases. Both
      questionnaires performed better for females based on comparison of the areas
      under the ROC curves. CONCLUSION: This study has demonstrated that the Urdu
      translations of both the PHQ and SRQ can be used as screening tests for
      depressive disorder in the Pakistani population. People with little or no
      education answer both somatic and psychological items with equal ease.
      Inconclusion, the PHQ does not appear to have any advantage over the SRQ.

PMID- 16967790
TI  - Earthquake relief experience of Aga Khan University trauma team.

PMID- 16967791
TI  - Efficiency of PA catheters in the ICU of a tertiary care hospital.
AB  - Existing randomized controlled trials on Pulmonary Artery Catheter (PAC)-guided
      strategies reveal a modest risk reduction that does reach statistical
      significance. An observational, prospective, controlled study was carried out in
      the ICU of a tertiary care hospital. Incidence, indications, complication rate
      and outcome of Pulmonary Artery (PA) catheter over a period of 3 months was
      looked at, comparing cases to matched controls. Despite being a limited study, it
      is obvious that the cost effectiveness and outcome of patients with the PA
      catheter seems ambiguous. In a developing country where resources are limited,
      thought must be given to the risk and benefit ratio of placing this invasive
      monitor and use of the information provided properly justified.

PMID- 16967792
TI  - A case of Taenia saginata (tape worm) infestation of the uterus presenting with
      abnormal vaginal bleeding.
AB  - There are many reported causes of abnormal uterine bleeding. We report an unusual
      case of uterine bleeding caused by tapeworm infestation, mimicking retained
      products of conception in a 35 year old multipara.

PMID- 16967793
TI  - Pleomorphic rhabdomyosarcoma within a choledochal cyst; a rare cause of
      obstructive jaundice.
AB  - Bile duct cysts are rare and of uncertain origin. Most have been reported in
      young females of Asian Descent. The long term complication of choledochal cysts
      includes malignant transformation in the epithelial lining of biliary tree.
      Histopathologically it is Cholangiocarcinoma in the majority of cases with poor
      long-term prognosis. However, Rhabdomyosarcoma associated with choledochal cyst
      in an adult is rarely reported before. The authors report one such case in an
      adult female patient who presented to us with features of obstructive jaundice.

PMID- 16967794
TI  - Laparoscopic assisted percutaneous nephrolithotomy (PCNL) in ectopic pelvic
      kidney.
AB  - We report the case of a patient with pain and an abdominal palpable mass whose
      tests showed a right pelvic kidney with a 4-cm stone in the renal pelvis. We
      describe the successful management through laparoscopic assisted percutaneous
      nephrolithotomy (PCNL) in ectopic pelvic kidney, stressing that this method is a
      minimally invasive therapeutic option in such cases.

PMID- 16967795
TI  - Rectal malakoplakia presenting as a mass and fistulous tract in a renal
      transplant patient.
AB  - Malakoplakia (MK) is a rare, chronic inflammatory disorder with characteristic
      morphologic features. It most commonly involves urogenital organs but can affect
      any organ system in the body. Gastrointestinal tract is the second common site of
      involvement. It commonly occurs in nontransplant patients but transplant patients
      are also vulnerable to it. We present a case report of a forty year old male
      renal transplant patient, who received a kidney from his brother with 1 haplotype
      and 4 antigen match. He was on regular post transplant follow up with stable
      graft function. Fifteen months post transplant he presented with the complaint of
      painful defecation, a swelling in the perianal region and inability to sit down
      properly. Biopsy examination showed malakoplakia with characteristic Michaelis
      Gutmann bodies. Culture of the tissue grew E Coli. Immunosuppression therapy was
      curtailed and patient was started on ciprofloxacin 500mg OD for 6 months. The
      lesions regressed completely after six months of the above therapy and the
      patient became completely symptoms free.

PMID- 16967796
TI  - Case presentation--first echelon for the young researcher.

PMID- 16967797
TI  - Indigenous and transcultural psychiatry; putting research into practice.

PMID- 16967798
TI  - Monotonic penalized-likelihood image reconstruction for X-ray fluorescence
      computed tomography.
AB  - In this paper, we derive a monotonic penalized-likelihood algorithm for image
      reconstruction in X-ray fluorescence computed tomography (XFCT) when the
      attenuation maps at the energies of the fluorescence X-rays are unknown. In XFCT,
      a sample is irradiated with pencil beams of monochromatic synchrotron radiation
      that stimulate the emission of fluorescence X-rays from atoms of elements whose K
      or L-edges lie below the energy of the stimulating beam. Scanning and rotating
      the object through the beam allows for acquisition of a tomographic dataset that
      can be used to reconstruct images of the distribution of the elements in
      question. XFCT is a stimulated emission tomography modality, and it is thus
      necessary to correct for attenuation of the incident and fluorescence photons.
      The attenuation map is, however, generally known only at the stimulating beam
      energy and not at the energies of the various fluorescence X-rays of interest. We
      have developed a penalized-likelihood image reconstruction strategy for this
      problem. The approach alternates between updating the distribution of a given
      element and updating the attenuation map for that element's fluorescence X-rays.
      The approach is guaranteed to increase the penalized likelihood at each
      iteration. Because the joint objective function is not necessarily concave, the
      approach may drive the solution to a local maximum. To encourage the algorithm to
      seek out a reasonable local maximum, we include in the objective function a prior
      that encourages a relationship, based on physical considerations, between the
      fluorescence attenuation map and the distribution of the element being
      reconstructed.

PMID- 16967799
TI  - Estimation of images and nonrigid deformations in gated emission CT.
AB  - In this paper, we propose and test a new iterative algorithm to simultaneously
      estimate the nonrigid motion vector fields and the emission images for a complete
      cardiac cycle in gated cardiac emission tomography. We model the myocardium as an
      elastic material whose motion does not generate large amounts of strain. As a
      result, our method is based on minimizing an objective function consisting of the
      negative logarithm of a maximum likelihood image reconstruction term, the
      standard biomechanical model of strain energy, and an image matching term that
      ensures a measure of agreement of intensities between frames. Simulations are
      obtained using data for the four-dimensional (4-D) NCAT phantom. The data models
      realistic noise levels in a typical gated myocardial perfusion SPECT study. We
      show that our simultaneous algorithm produces images with improved spatial
      resolution characteristics and noise properties compared with those obtained from
      postsmoothed 4-D maximum likelihood methods. The simulations also demonstrate
      improved motion estimates over motion estimation using independently
      reconstructed images.

PMID- 16967800
TI  - Learning-based deformable registration of MR brain images.
AB  - This paper presents a learning-based method for deformable registration of
      magnetic resonance (MR) brain images. There are two novelties in the proposed
      registration method. First, a set of best-scale geometric features are selected
      for each point in the brain, in order to facilitate correspondence detection
      during the registration procedure. This is achieved by optimizing an energy
      function that requires each point to have its best-scale geometric features
      consistent over the corresponding points in the training samples, and at the same
      time distinctive from those of nearby points in the neighborhood. Second, the
      active points used to drive the brain registration are hierarchically selected
      during the registration procedure, based on their saliency and consistency
      measures. That is, the image points with salient and consistent features (across
      different individuals) are considered for the initial registration of two images,
      while other less salient and consistent points join the registration procedure
      later. By incorporating these two novel strategies into the framework of the
      HAMMER registration algorithm, the registration accuracy has been improved
      according to the results on simulated brain data, and also visible improvement is
      observed particularly in the cortical regions of real brain data.

PMID- 16967801
TI  - Automated contour detection in X-ray left ventricular angiograms using multiview
      active appearance models and dynamic programming.
AB  - This paper describes a new approach to the automated segmentation of X-ray left
      ventricular (LV) angiograms, based on active appearance models (AAMs) and dynamic
      programming. A coupling of shape and texture information between the end
      diastolic (ED) and end-systolic (ES) frame was achieved by constructing a
      multiview AAM. Over-constraining of the model was compensated for by employing
      dynamic programming, integrating both intensity and motion features in the cost
      function. Two applications are compared: a semi-automatic method with manual
      model initialization, and a fully automatic algorithm. The first proved to be
      highly robust and accurate, demonstrating high clinical relevance. Based on
      experiments involving 70 patient data sets, the algorithm's success rate was 100%
      for ED and 99% for ES, with average unsigned border positioning errors of 0.68 mm
      for ED and 1.45 mm for ES. Calculated volumes were accurate and unbiased. The
      fully automatic algorithm, with intrinsically less user interaction was less
      robust, but showed a high potential, mostly due to a controlled gradient descent
      in updating the model parameters. The success rate of the fully automatic method
      was 91% for ED and 83% for ES, with average unsigned border positioning errors of
      0.79 mm for ED and 1.55 mm for ES.

PMID- 16967802
TI  - Tomographic reconstruction using an adaptive tetrahedral mesh defined by a point
      cloud.
AB  - Medical images in nuclear medicine are commonly represented in three dimensions
      as a stack of two-dimensional images that are reconstructed from tomographic
      projections. Although natural and straightforward, this may not be an optimal
      visual representation for performing various diagnostic tasks. A method for three
      dimensional (3-D) tomographic reconstruction is developed using a point cloud
      image representation. A point cloud is a set of points (nodes) in space, where
      each node of the point cloud is characterized by its position and intensity. The
      density of the nodes determines the local resolution allowing for the modeling of
      different parts of the image with different resolution. The reconstructed volume,
      which in general could be of any resolution, size, shape, and topology, is
      represented by a set of nonoverlapping tetrahedra defined by the nodes. The
      intensity at any point within the volume is defined by linearly interpolating
      inside a tetrahedron from the values at the four nodes that define the
      tetrahedron. This approach creates a continuous piecewise linear intensity over
      the reconstruction domain. The reconstruction provides a distinct multiresolution
      representation, which is designed to accurately and efficiently represent the 3-D
      image. The method is applicable to the acquisition of any tomographic geometry,
      such as parallel-, fan-, and cone-beam; and the reconstruction procedure can also
      model the physics of the image detection process. An efficient method for
      evaluating the system projection matrix is presented. The system matrix is used
      in an iterative algorithm to reconstruct both the intensity and location of the
      distribution of points in the point cloud. Examples of the reconstruction of
      projection data generated by computer simulations and projection data
      experimentally acquired using a Jaszczak cardiac torso phantom are presented.
      This work creates a framework for voxel-less multiresolution representation of
      images in nuclear medicine.

PMID- 16967803
TI  - Electrode boundary conditions and experimental validation for BEM-based EIT
      forward and inverse solutions.
AB  - In this paper, we present theoretical developments and experimental results for
      the problem of estimating the conductivity map inside a volume using electrical
      impedance tomography (EIT) when the boundary locations of any internal
      inhomogeneities are known. We describe boundary element method (BEM)
      implementations of advanced electrode models for the forward problem of EIT. We
      then use them in the inverse problem with known internal boundaries and derive
      the associated Jacobians. We report on the results of two EIT phantom studies,
      one using a homogeneous cubical tank, and one using a cylindrical tank with agar
      conductivity inhomogeneities. We test both the accuracy of our BEM forward model,
      including the electrode models, as well as our inverse solution, against the
      measured data. Results show good agreement between measured values and both
      forward-computed tank voltages and inverse-computed conductivities; for instance,
      in a phantom experiment, we reconstructed the conductivities of three agar
      objects inside a cylindrical tank with an error less than 2% of their true value.

PMID- 16967804
TI  - Efficient transmission of compressed data for remote volume visualization.
AB  - One of the goals of telemedicine is to enable remote visualization and browsing
      of medical volumes. There is a need to employ scalable compression schemes and
      efficient client-server models to obtain interactivity and an enhanced viewing
      experience. First, we present a scheme that uses JPEG2000 and JPIP (JPEG2000
      Interactive Protocol) to transmit data in a multi-resolution and progressive
      fashion. The server exploits the spatial locality offered by the wavelet
      transform and packet indexing information to transmit, in so far as possible,
      compressed volume data relevant to the clients query. Once the client identifies
      its volume of interest (VOI), the volume is refined progressively within the VOI
      from an initial lossy to a final lossless representation. Contextual background
      information can also be made available having quality fading away from the VOI.
      Second, we present a prioritization that enables the client to progressively
      visualize scene content from a compressed file. In our specific example, the
      client is able to make requests to progressively receive data corresponding to
      any tissue type. The server is now capable of reordering the same compressed data
      file on the fly to serve data packets prioritized as per the client's request.
      Lastly, we describe the effect of compression parameters on compression ratio,
      decoding times and interactivity. We also present suggestions for optimizing
      JPEG2000 for remote volume visualization and volume browsing applications. The
      resulting system is ideally suited for client-server applications with the server
      maintaining the compressed volume data, to be browsed by a client with a low
      bandwidth constraint.

PMID- 16967805
TI  - Segmentation of retinal blood vessels by combining the detection of centerlines
      and morphological reconstruction.
AB  - This paper presents an automated method for the segmentation of the vascular
      network in retinal images. The algorithm starts with the extraction of vessel
      centerlines, which are used as guidelines for the subsequent vessel filling
      phase. For this purpose, the outputs of four directional differential operators
      are processed in order to select connected sets of candidate points to be further
      classified as centerline pixels using vessel derived features. The final
      segmentation is obtained using an iterative region growing method that integrates
      the contents of several binary images resulting from vessel width dependent
      morphological filters. Our approach was tested on two publicly available
      databases and its results are compared with recently published methods. The
      results demonstrate that our algorithm outperforms other solutions and
      approximates the average accuracy of a human observer without a significant
      degradation of sensitivity and specificity.

PMID- 16967806
TI  - Retinal vessel segmentation using the 2-D Gabor wavelet and supervised
      classification.
AB  - We present a method for automated segmentation of the vasculature in retinal
      images. The method produces segmentations by classifying each image pixel as
      vessel or nonvessel, based on the pixel's feature vector. Feature vectors are
      composed of the pixel's intensity and two-dimensional Gabor wavelet transform
      responses taken at multiple scales. The Gabor wavelet is capable of tuning to
      specific frequencies, thus allowing noise filtering and vessel enhancement in a
      single step. We use a Bayesian classifier with class-conditional probability
      density functions (likelihoods) described as Gaussian mixtures, yielding a fast
      classification, while being able to model complex decision surfaces. The
      probability distributions are estimated based on a training set of labeled pixels
      obtained from manual segmentations. The method's performance is evaluated on
      publicly available DRIVE (Staal et al., 2004) and STARE (Hoover et al., 2000)
      databases of manually labeled images. On the DRIVE database, it achieves an area
      under the receiver operating characteristic curve of 0.9614, being slightly
      superior than that presented by state-of-the-art approaches. We are making our
      implementation available as open source MATLAB scripts for researchers interested
      in implementation details, evaluation, or development of methods.

PMID- 16967807
TI  - Automated microaneurysm detection using local contrast normalization and local
      vessel detection.
AB  - Screening programs using retinal photography for the detection of diabetic eye
      disease are being introduced in the UK and elsewhere. Automatic grading of the
      images is being considered by health boards so that the human grading task is
      reduced. Microaneurysms (MAs) are the earliest sign of this disease and so are
      very important for classifying whether images show signs of retinopathy. This
      paper describes automatic methods for MA detection and shows how image contrast
      normalization can improve the ability to distinguish between MAs and other dots
      that occur on the retina. Various methods for contrast normalization are
      compared. Best results were obtained with a method that uses the watershed
      transform to derive a region that contains no vessels or other lesions. Dots
      within vessels are handled successfully using a local vessel detection technique.
      Results are presented for detection of individual MAs and for detection of images
      containing MAs. Images containing MAs are detected with sensitivity 85.4% and
      specificity 83.1%.

PMID- 16967808
TI  - Constrained Gaussian mixture model framework for automatic segmentation of MR
      brain images.
AB  - An automated algorithm for tissue segmentation of noisy, low-contrast magnetic
      resonance (MR) images of the brain is presented. A mixture model composed of a
      large number of Gaussians is used to represent the brain image. Each tissue is
      represented by a large number of Gaussian components to capture the complex
      tissue spatial layout. The intensity of a tissue is considered a global feature
      and is incorporated into the model through tying of all the related Gaussian
      parameters. The expectation-maximization (EM) algorithm is utilized to learn the
      parameter-tied, constrained Gaussian mixture model. An elaborate initialization
      scheme is suggested to link the set of Gaussians per tissue type, such that each
      Gaussian in the set has similar intensity characteristics with minimal
      overlapping spatial supports. Segmentation of the brain image is achieved by the
      affiliation of each voxel to the component of the model that maximized the a
      posteriori probability. The presented algorithm is used to segment three
      dimensional, T1-weighted, simulated and real MR images of the brain into three
      different tissues, under varying noise conditions. Results are compared with
      state-of-the-art algorithms in the literature. The algorithm does not use an
      atlas for initialization or parameter learning. Registration processes are
      therefore not required and the applicability of the framework can be extended to
      diseased brains and neonatal brains.

PMID- 16967809
TI  - Vaccination coverage survey in Dhaka District.
AB  - A survey was conducted in Dhaka District to measure the level of routine
      immunization coverage of children (12-23 months), to assess the tetanus toxoid
      (TT) immunization coverage among mothers of children (12-23 month), to evaluate
      EPI program continuity (dropout rates) and quality (percent of Invalid doses,
      vaccination card availability etc.) For this purpose, a thirty cluster cross
      sectional survey was conducted in October 2002 to assess the immunization
      coverage in Dhaka. In this survey 30 clusters were randomly selected from a list
      of villages in 63 Unions of Dhaka following probability proportion to size (PPS)
      sampling procedure. A total of 210 children was studied using pre-tested
      structured questionnaire. Descriptive statistics was employed using software SPSS
      package for data analysis. The study showed that the routine immunization
      coverage in Dhaka among children by 12 months of age by card + history was 97%
      for BCG, 97% for Diphtheria, Pertussis Tetanus (DPT 1) and Oral Polio Vaccine
      (OPV 1), 75% for DPT3 and OPV3 and 67% for measles. Sixty six percent of all
      children surveyed had received valid doses of all vaccines by 12 months (fully
      immunized child). Programme access as measured by crude DPT1 coverage was better
      in Keranigonj (97%). Vaccination cards retention rate for children was 84%.
      Invalid DPT (1,2 or 3) doses were given to 25% of vaccinated children; 18% of
      measles doses were invalid. Surprisingly, major cause for invalid doses were not
      due to early immunizations or due to card lost but for giving tick in the card,
      instead of writing a valid date. DPT1 and DPT3 and DPT1- Measles drop out rates
      were 5% and 13% respectively. Major reason parents gave for never vaccinating
      their children (zero dose children) was (43%), major reasons for incomplete
      vaccination was lack of knowledge regarding subsequent doses (46%). TT surveys
      were also conducted for mothers of the children surveyed for vaccination coverage
      (mothers between 15-49 year old). Valid TT 1-5 coverage by card+ history was 97%,
      55%, 44%, 24% and 11%, respectively. Card retention rate for TT was 67%. The
      findings of this study revealed that access to child and TT immunizations were
      good. But high dropouts and invalid doses reduced these percentages of fully
      immunized child to 66%. Programmatic strategy must be undertaken to reduce the
      existing high dropout rate in both child and TT immunizations.

PMID- 16967810
TI  - Efficacy of terazosin and finasteride in symptomatic benign prostatic
      hyperplasia: A comparative study.
AB  - Medical treatment for symptomatic Benign Prostatic Hyperplasia (BPH) has become
      popular for the last few years. This study was designed to find out and compare
      the efficacy of terazosin, a alpha1 adrenoceptor blocker and finasteride, a
      5alpha-reductase inhibitor in symptomatic BPH. A total of 60 patients (30 in
      terazosin group and 30 finasteride group) of symptomatic BPH were selected.
      Terazosin group received 1 mg daily at bedtime for 3 days, 2 mg at bedtime for 7
      days, thereafter 5 mg at bedtime daily for 6 months. Finasteride group received 5
      mg once daily. In terazosin treated patients, improvement after 3 months were as
      follows, IPSS 3.93 +/- .74 points reduction, Qmax 2.13 +/- .68 ml/s increase,
      post-voided residual urine volume (PVR) 20.67 +/- 10.56 ml reduction
      (significant, p<0.001) and prostate volume 0.57 +/- 1.54 ml reduction (not
      significant). Similar statistical differences were observed at 6 months follow
      up. In finasteride treated patients, improvements after 3 months were as follows,
      International Prostate Symptom Score (IPSS) 1.38 +/- .63 points reduction, Qmax
      0.55 +/- 0.78 ml/s increase, PVR 5.93 +/- 7.64 ml reduction (significant,
      p<0.001) and prostate volume 0.17 +/- 5.6 ml reduction (non-significant). At 6
      month follow up statistical differences were significant in all parameters
      including prostate volume 4.57 +/- 5.30 ml reduction (p<0.001). In comparison,
      statistically significant superiority of terazosin over finasteride was found in
      improving IPSS, Qmax and PVR in both follow up visits. But terazosin had
      nonsignificant effect in reducing prostate volume; in contrast, finasteride had
      significant effect in second visit. It can be concluded from this study that
      terazosin 5mg once daily is effective in mild to moderate cases of symptomatic
      BPH. On the other hand, finasteride 5mg once daily may be useful in large
      prostate and to be given for at least 6 months.

PMID- 16967811
TI  - Diabetic neuropathy and zinc therapy.
AB  - This was a double blind study conducted on 60 subjects; 20 age and sex matched
      healthy controls (Group-I), 20 patients of diabetes mellitus with neuropathy who
      received placebo for 6 weeks (Group-IIA); and 20 patients of diabetes mellitus
      with neuropathy who were given oral 660 mg zinc sulphate for 6 weeks (Group-IIB).
      Serum zinc level, fasting blood sugar (FBS), blood sugar 2 hour after breakfast
      (2HABF) and motor nerve conduction velocity (MNCV) were estimated on day 0 and
      after 6 weeks in all subjects. Serum zinc levels were significantly low (p<0.001)
      in group II-A and II-B as compared to healthy controls (group-I) at base line.
      After 6 weeks the changes in pre and post therapy values of FBS, 2HABF and MNCV
      (median and common peroneal nerve) were highly significant (p<0.001) for group II
      B alone with insignificant change (p>0.05) in group II-A. Therefore, zinc therapy
      helps in achieving better glycemic control and improvement in peripheral
      neuropathy as assessed by MNCV.

PMID- 16967812
TI  - Noise level in different places of Dhaka Metropolitan City (DMC) and noise
      induced hearing loss (NIHL) in Dhaka City dwellers.
AB  - A cross sectional, exploratory study was designed at "National Center for Hearing
      and Speech for Children" (NCHSC), Dhaka, Bangladesh, from May 2001 to June 2002,
      with a view to determine the average noise level in different places of Dhaka
      Metropolitan City (DMC), and also aiming at evaluating the extent of Noise
      induced Hearing Loss (NIHL) in different groups of city dwellers and finally a
      base line information. A total of 32 places in DMC were selected randomly. The
      highest noise level recorded 104 dB at Sayedabad bus terminal and the lowest 68
      dB in Banani and Baridhara residential area. In silent zone of DMC, average noise
      level was 79 dB, in residential zone 72 dB, in commercial zone 90 dB, and in
      mixed zone average noise level was recorded at 91 dB. Measured noise levels were
      more than acceptable and permissible levels in all places of DMC. A total of 312
      persons aged between 15-45 years (mean age- 24.64 years) were enrolled for the
      study as per inclusion criteria. Gender-wise male were 211(67.62%) and female
      were 101(32.57%). Profession-wise Automobile drivers were 57(18.26 %), Garment
      workers 58(18.55 %), City dwellers 72(23.07%), Students 72(23.07%), Traffic
      polices 12(3.85%), Hawkers and Road side shopkeepers were 41(13.1%). Definite
      noise notch (>25dB) at 4KHz observed in 33(10.58%) audiogram of persons under
      study. Automobile drivers, Traffic polices, Road side hawkers and Shop keepers,
      Garment workers are mostly affected were 17.54%, 16.4%, 12.09% and 12.06%
      respectively. A total of 201 persons (64.42%) were not aware of their hearing
      impairment, 244(78%) of the person had poor level of knowledge regarding bad
      effects of noise on health and about protective means available. Amongst persons
      (33) found to have NIHL did not use any protective device.

PMID- 16967813
TI  - Use of parenteral magnesium sulphate in eclampsia and severe pre-eclampsia cases
      in a rural set up of Bangladesh.
AB  - This was a quasi-experimental interventional study to see the role of injection
      magnesium sulphate in eclampsia and severe pre-eclampsia patients at community
      level in a rural set up before referral to the hospital. This study was conducted
      on 265 cases of eclampsia and severe pre-eclampsia over a period of six months
      from July 2001 to December 2001. Among 265 cases, 133 were in intervention group
      who had received loading dose of injection magnesium sulphate before referral and
      the rest 132 were in non-intervention group, had not received injection magnesium
      sulphate before admision in hospital. The number (mean +/- SD) of convulsion
      before treatment in intervention and non-intervention groups were 4.7 +/- 2.64 &
      6.86 +/- 2.97 respectively. Recurrence of fits observed more in non-intervention
      group and the difference was statistically significant (p<.001). Mean (+/- SD)
      time taken to regain full consciousness was 12.0+9.6 and 17.4+7.4 hours in the
      intervention and non-intervention group respectively (p<.05). Control of
      convulsion by loading dose of 10 gm of injection magnesium sulphate was achieved
      in 94.0% of the intervention group and 74.0% in non-intervention group. There was
      only 3(2.3%) maternal death in study group whereas in non-intervention group
      maternal death was 14(10.4%) and the difference was highly significant (p<.005).
      Fourteen (13.7%) babies were still born in intervention group and 21(20%) in non
      intervention group. The difference was statistically highly significant (p<.001).
      Remarkable achievements were obtained through use of magnesium sulphate at the
      community level at rural setting among the eclampsia and severe pre-eclampsia
      cases.

PMID- 16967814
TI  - Effect rHuEpo on predialysis CRF patients: study of 45 cases.
AB  - Forty five (24 male & 21 female) moderate to severe degree of predialysis CRF
      patients were prospectively studied over a period of 6 months (July- December,
      2004) to see the effect of Recombinant Human Erythropoietin (rHuEpo/EPO) therapy
      on renal anaemia, progression of renal excretory function & quality of life at 3
      and 6 months intervals from the starting of EPO therapy. Mean +/- SD age of the
      patients was 56 +/- 12 (30-77 yrs) and causes of CRF were Diabetic Nephropathy
      (DN)=15 (33%), Chronic Glomerulonephritis (CGN) =14(31%), Hypertension
      (HTN)=11(21%), Chronic Pyelonephritis (CPN)=03 (6.5%) and Obstructive Uropathy
      (OU)=02 (4.5%). Doses of rHuEpo was 80-100 IU/k week subcutaneously (SC) until
      the target Hb 11gm% & Hct 30% were achieved; there after the dose was titrated as
      appropriate. Serum Iron & Ferritin levels were also kept within normal reference
      level by iron therapy during the study period. Mean +/- SD base line (before
      starting EPO therapy) level of haemoblobin were 8.4 +/- 0.81(gm%), Hct 27.86 +/-
      1.6 (%), blood urea 21.72 +/- 10.5 (mmol/L), S. creatinine 431.93 +/- 228.79
      (mmol/L) & Ccr. 21.25 +/- 10 mum respectively. The results showed that
      significant improvement of haemoglobin level occurred (gm%) from 8.4 +/- 0.81
      (gm%) to 9.51 +/- 1.02 (p<0.001) at 3 months and 8.4 +/- 0.81 to 11.10 +/- 1.4,
      (p<0.001) at 6 months interval. Haematocrit (Hct%) value also significantly
      increased from 27.86 +/- 1.5 to 30.57 +/- 3.62, (p<0.001) at 3 months and 27.86
      +/- 1.5 to 32.81 +/- 3.92 (p<0.001) at 6 months of EPO therapy. Mean blood urea
      and S. creatinine levels decreased from base line level during the study period
      but did not show any statistical significance. There was no significant side
      effects like uncontrolled hypertension, seizure or hyperviscosity syndrome in any
      of the study population. The quality of life in terms of improvement of physical
      ability and sense of well being were also improved in all the study patients. In
      conclusion, this study showed that the effect of rHuEpo therapy is beneficial for
      the correction of renal anaemia, can delay the progression of renal failure and
      improvement of overall quality of life in predialysis CRF patients.

PMID- 16967815
TI  - Generation and characterisation of monoclonal antibodies specific to Plasmodium
      falciparum enolase.
AB  - BACKGROUND AND OBJECTIVES: Glycolysis is the sole source of energy for the
      intraerythrocytic stages of Plasmodium falciparum, making glycolytic enzymes
      putative therapeutic targets. Enolase, a single copy gene in P. falciparum is one
      such enzyme whose activity is elevated approximately 10-15 fold in infected
      RBC's. It holds the possibility of having multiple biological functions in the
      parasite and hence can be a suitable candidate for diagnostic and
      chemotherapeutic purposes. METHODS: We have aimed at generating parasite-specific
      reagents in the form of monoclonal antibodies. We have raised monoclonal
      antibodies against the recombinant P. falciparum enolase. RESULTS: Two IgG
      monoclonals were obtained with 1:1000 titre and specific for P. falciparum
      enolase. Apicomplexan parasites including P. falciparum enolase has a plant like
      pentapeptide sequence (104EWGWS108) which is uniquely different from the host
      counterpart. A peptide spanning this pentapeptide region (ELDGSKNEWGWSKSK)
      coupled to BSA was used to raise parasite-specific antibody. Four monoclonals
      were obtained with 1:1000 titre and of IgM isotype. INTERPRETATION AND
      CONCLUSION: All the monoclonals are specific for P. falciparum enolase and one of
      them display reactivity against native P. falciparum enolase signifying this
      pentapeptide to be surface exposed and immunogenic.

PMID- 16967816
TI  - Comparing the results of light microscopy with the results of PCR method in the
      diagnosis of Plasmodium vivax.
AB  - BACKGROUND AND OBJECTIVES: Although polymerase chain reaction (PCR) is a new
      technique in the diagnosis of malaria with very high accuracy; light microscopy
      is still conventional diagnostic method in Iran. In this study we checked the
      accuracy of light microscopy using the results of PCR as gold standard in Iran.
      METHODS: The blood samples were collected from 124 febrile cases in Kahnooj
      district. The blood slides were read by microscopists, and double checked by
      experts in provincial referral laboratory. DNA samples were processed by PCR to
      amplify species-specific sequences of 18s subunit ribosomal ribonucleic acid
      (18ssrRNA) genes of Plasmodium vivax and P. falciparum. RESULTS: The sensitivity
      and specificity of microscopy in the detection of Plasmodium spp infection were
      77% (95% CI: 46-94%) and 100% (95% CI: 95-100%), correspondingly. Also, the
      estimated positive and negative predictive values were 100% (95% CI: 66-100%) and
      97% (95% CI: 91-99%), respectively. INTERPRETATION AND CONCLUSION: According to
      these results, we believe that the accuracy of light microscopy in the diagnosis
      of malaria in Kahnooj was acceptable. Expert micorscopists in endemic areas of
      Iran such as Kahnooj and available equipments in one hand and expensive PCR test
      on the other hand may convince that in current situation we do not have to change
      the diagnostic method.

PMID- 16967817
TI  - The role of private drug vendors as malaria treatment providers in selected
      malaria endemic areas of Sri Lanka.
AB  - BACKGROUND AND OBJECTIVES: The involvement of private drug vendors in malaria
      treatment is particularly high in developing countries and understanding their
      practices and knowledge about antimalarials and malaria treatment will aid in
      devising strategies to increase the correct use of antimalarials and improve
      adherence to the government's malaria drug policy. Results of a study on the
      knowledge and practices of the private drug vendors conducted in seven districts
      in Sri Lanka, mostly in malarious areas are presented. METHODS: Data on awareness
      of government's malaria drug policy, practice of issuing antimalarials, knowledge
      about malaria and antimalarial drugs were collected from the drug vendors using
      pre-tested questionnaire in vernacular language. Data were statistically analysed
      using Stata 8.2. Chi-square test was carried out for individual explanatory
      variables and a logistic regression model was applied taking all response
      variables as binary outcome. RESULTS: Vendors' knowledge on antimalarials was
      poor with 58% of the vendors being unaware of the government malaria drug policy
      in the country. Also, the advice provided to customers buying antimalarials was
      limited. However, the majority of the private vendors emphasised that they were
      aware of the importance of case confirmation before treatment as stressed in the
      national policy. Although, the vendors did not have a high awareness of national
      drug policies they were only found selling chloroquine and primaquine as
      recommended by the Ministry of Health. INTERPRETATION AND CONCLUSION: In recent
      years Sri Lanka, as a whole, has experienced very little malaria. The reduction
      in demand for antimalarials due to low incidence levels may have influenced the
      knowledge and awareness on antimalarials and government drug policies. However,
      since low levels of malaria do not guarantee that epidemics will not occur,
      attempts to educate private drug vendors as a part of an organised control
      programmes are of major importance.

PMID- 16967818
TI  - Predatory activity of Rhantus sikkimensis and larvae of Toxorhynchites splendens
      on mosquito larvae in Darjeeling, India.
AB  - BACKGROUND AND OBJECTIVES: Predation potential of the dytiscid beetle, Rhantus
      sikkimensis Regimbart 1899 and the larvae of Toxorhynchites splendens Wiedemann
      1819 occurring along with the larval stages of the mosquitoes in the annual
      lentic water bodies of Darjeeling was evaluated using the larvae of Culex
      quinquefasciatus Say 1823 as preys, in the laboratory under simulated natural
      conditions. METHODS: Field collected R. sikkimensis and larvae of Tx. splendens
      were offered IV instar larvae of Cx. quinquefasciatus to observe the rate of
      predation, at varying prey and predator densities. Based on the data obtained on
      the predation for a period of three consecutive days, two indices of predation,
      predatory impact (PI) and clearance rate (CR) values were estimated, and compared
      between the predator species. RESULTS: The rate of predation of IV instar Cx.
      quinquefasciatus larvae by R. sikkimensis ranged between 21.56 and 86.89 larvae
      per day, depending on the prey and predator densities. The PI value remained
      between 18.67 and 35.33 larvae/day depending on prey densities, while the CR
      ranged between 2.21 and 2.23 larvae litres/day/predator. Compared to these, the
      Tx. splendens larvae consumed the prey larvae at the rate of 0.67 to 34.22 larvae
      per day, depending on the prey and predator densities. The PI value ranged
      between 7.67 and 11.33 larvae/day, and the CR value ranged between 1.41 and 1.76
      larvae litres/day/predator. The rate of predation, CR values and PI values of R.
      sikkimensis and Tx. splendens varied significantly. INTERPRETATION AND
      CONCLUSION: Both the predators R. sikkimensis and larvae of Tx. splendens can
      consume a good number of mosquito larvae, though the rate of consumption between
      the two predators vary owing to the difference in the life history traits and
      features. It can be assumed that these predators play an important role in larval
      population regulation of mosquitoes and thereby impart an effect on species
      composition and interactions in the aquatic insect communities of Darjeeling
      Hills, India.

PMID- 16967819
TI  - An observation on correlation between rainfall and the prevalence of clinical
      cases of dengue in Thailand.
AB  - BACKGROUND AND OBJECTIVES: An investigation was carried out in Thailand to study
      the correlation between rainfall and prevalence of dengue infection during 2002
      03, which can be used for prevention and control of the disease. METHODS:
      Rainfall data (2002-03) collected from Ministry of Public Health were utilised
      for transformation of the infection and the rainfall data were derived from Royal
      Irrigation Department, Thailand. The correlation between the rainfall and the
      prevalence of dengue was assessed by regression analysis. RESULTS: The least
      square equation plot prevalence (y) versus rainfall (x) is y = 3.0x + 4.6 (r =
      0.78, p < 0.05) (r = 0.68, p < 0.05). INTERPRETATION AND CONCLUSION: The study
      indicated that the prevalence of dengue infection in Thailand may depend on
      rainfall. Therefore, the surveillance and control of mosquito should be
      intensified during the period with high rainfall is recommended. However, the
      other confounding factors like ambient temperature and humidity which also
      determine the transmission of dengue should be looked into, before concluding
      that the increased prevalence is a result of rainfall alone. Further, similar
      studies to assess the correlation between the rainfall and prevalence of
      infection in the other countries are required to confirm these observations.

PMID- 16967821
TI  - Synchronic macrophage response and Plasmodium falciparum malaria.

PMID- 16967820
TI  - Relationship between malaria and filariasis transmission indices in an endemic
      area along the Kenyan Coast.
AB  - BACKGROUND AND OBJECTIVES: An entomological survey was conducted to determine the
      relationship between malaria and lymphatic filariasis transmission by Anopheles
      gambiae s.l. and An. funestus in two inland villages along the Kenyan coast.
      METHODS: Mosquitoes were sampled inside houses by pyrethrum spray sheet
      collection (PSC). In the laboratory, the mosquitoes were sorted to species,
      dissected for examination of filarial infection and the anophelines later tested
      for Plasmodium falciparum circumsporozoite proteins by an enzyme-linked
      immunosorbent assay (ELISA). RESULTS: From a total of 2,032 female mosquitoes
      collected indoors, An. gambiae s.l constituted 94.4% while the remaining 5.6%
      comprised of An. funestus and Culex quinquefasciatus. None of the Cx.
      quinquefasciatus was positive for filarial worms. P. falciparum sporozoite rate
      for An. gambiae s.l. from both villages was significantly higher than Wuchereria
      bancrofti infectivity rate. Similarly, the entomological inoculation rate for An.
      gambiae s.l. was significantly higher than the corresponding W. bancrofti
      infective biting rate and transmission potential for both the villages. Mass
      treatment of people with filaricidal drugs in Shakahola in the ongoing global
      elimination of lymphatic filariasis campaign seemed to have reduced the indices
      of filariasis transmission but had no effect on malaria transmission.
      INTERPRETATION AND CONCLUSION: These results indicate the intensity of malaria
      transmission by anophelines to be much higher than that of lymphatic filariasis
      in areas where both diseases co-exist and re-emphasise the need to integrate the
      control of the two diseases in such areas.

PMID- 16967822
TI  - Mosquito larvicidal properties of Momordica charantia Linn (family:
      Cucurbitaceae).

PMID- 16967823
TI  - Quality control of mosquito insecticide treated nets as a preventive measure.

PMID- 16967824
TI  - Mortality of iron-steel workers in Anshan, China: a retrospective cohort study.
AB  - Foundry workers have increased mortality and morbidity risks from numerous
      causes, including various cancers. A retrospective Chinese iron-steel cohort
      study was conducted to examine the mortality effects of exposure to foundry work.
      Standardized mortality ratios (SMRs) and standardized rate ratios (SRRs) were
      calculated to evaluate mortality risks among male workers with exposure to 15
      hazardous factors, adjusting for confounders. During 14 years of follow-up,
      13,363 of 121,846 male workers died. SMR analysis showed a healthy-worker effect
      in comparison with the general population. SRR analysis showed increased risks
      for all causes, all neoplasms, and others among the exposed workers compared with
      non-exposed blue-collar workers. Combined exposure to polycyclic aromatic
      hydrocarbons and two or more dusts increased the risks of lung cancer (SRR = 654;
      95% CI: 113-3,780) and other malignancies. Foundry work has adverse health
      effects, including carcinogenic risks.

PMID- 16967826
TI  - Neurocognitive screening of mercury-exposed children of Andean gold miners.
AB  - Performance on Raven's Coloured Progressive Matrices (RCPM) test of visual
      spatial reasoning was used to evaluate the effects of mercury (Hg) exposure on 73
      Andean children aged 5 to 11 years (mean: 8.4) living in the Nambija and
      Portovelo gold mining areas of Ecuador, where Hg is widely used in amalgamation.
      Mean levels of Hg found in blood (Hg(B)), urine (Hg(U)), and hair (Hg(H)) samples
      were 5.1 microg/L (SD: 2.4; range: 1-10 microg/L), 13.3 microg/L (SD: 25.9;
      range: 1-166 microg/L), and 8.5 microg/g (SD: 22.8; range: 1-135 microg/g),
      respectively. Of the children in the Nambija area 67-84.9% had abnormal RCPM
      standard scores (i.e., < or = 25%tile), depending on the test norm used in the
      data analysis. Higher standard scores for Peruvian (t = 4.77; p = < 0.0001) and
      Puerto Rican (t = 4.51; p = < 0.0001) norms than for U.S. norms suggested a
      linguistic influence. No difference was found between Peruvian and Puerto Rican
      norms (t = 0.832; p = < 0.408), which showed a significant positive correlation
      (r = 0.915, p = < 0.0001). Children with abnormal Hg(B) and Hg(H) levels had
      significantly lower scores on the RCPM subtest B than did children with nontoxic
      Hg levels (t = -2.16; p = < 0.034). These results suggest that a substantial
      number of Hg-exposed children in the Nambija study area have neurocognitive
      deficits in visual-spatial reasoning.

PMID- 16967825
TI  - Sequential radiologic and functional pulmonary changes in patients with paraquat
      intoxication.
AB  - The sequential changes of paraquat-induced pulmonary damage were studied using
      high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) in
      long-term follow-up. Among the cohort of 27 patients who had ingested paraquat,
      the HRCT findings showed a normal (n = 14) and an abnormal group (n = 13).
      Increased paraquat ingestion in the abnormal group was associated with more rapid
      and severe pulmonary changes. Ground-glass opacity on HRCT peaked on day 7 after
      ingestion. Between 2 weeks and 1 month, consolidation increased and pulmonary
      fibrosis progressed, and slow improvements were observed for up to six months.
      Compared with the PFT results obtained at 1 and 6.5 months, FVC, FEV1, and
      diffusing capacity all improved slightly. Lung changes after paraquat
      intoxication are functionally and radiologically reversible following treatment.

PMID- 16967827
TI  - Mercury reduction in Munhena, Mozambique: homemade solutions and the social
      context for change.
AB  - The health and environmental impacts of artisanal gold mining are of growing
      concern in Munhena, Mozambique, where more than 12,000 people are involved in
      such activities. Gold is extracted using mercury amalgamation, posing a
      considerable threat to human and environmental health. A pilot project
      ascertained the feasibility of reducing mercury use and emissions by promoting
      control measures utilizing local resources. Retorts were fabricated with local
      materials. Training workshops introduced the homemade retorts, and a portable
      mercury monitor revealed effective mercury reduction. Barriers to widespread
      technology adoption include poverty, lack of knowledge and trust, and the free
      supply of mercury from private gold buyers. Homemade retorts are inexpensive and
      effective, and miners could benefit by building community amalgamation centers.
      The government could play a greater role in gold purchasing to reduce mercury
      pollution.

PMID- 16967828
TI  - Association between blood lead level and blood pressure in aborigines and others
      in central Taiwan.
AB  - To investigate the relationship between the blood lead level (BLL) and blood
      pressure among aborigines and non-aborigines in central Taiwan, a community-based
      survey that included demographic data, medical history, and blood chemistry
      analyses was conducted among 2,565 adults during an annual health examination.
      BLLs were analyzed using a graphite furnace atomic absorption spectrometer (AAS).
      There was a dose response among the non-aborigines (high BLL odds ratio = 2.97,
      compared with low BLL) but not among aborigines. Based on multiple linear
      regression models, BLLs were positively correlated with both systolic (an
      increase of 0.85 mm Hg/microg/dL) and diastolic (an increase of 0.48 mm
      Hg/microg/dL) blood pressures after adjusting for age, gender, ethnic group,
      alcohol consumption, and body mass index. BLLs were higher among aborigines than
      non-aborigines and were significantly correlated with blood pressure,
      particularly systolic pressure. The association should be considered causal.

PMID- 16967829
TI  - Use of pesticides and its impact on health of farmers in South India.
AB  - The relationship between extent of pesticide use and signs and symptoms of
      illnesses due to exposure was assessed in a cross-sectional survey of 631 farmers
      (537 men and 94 women) in South India. Responses to questionnaires showed that
      433 farmers (68.6%) sprayed pesticides themselves and were thus directly exposed.
      More than 75% used moderately or highly hazardous pesticides; 88% used no
      protection while handling pesticides. About 50% of sprayers mixed different
      brands. Retailers were the source of information about pesticides for 56%. The
      farmers reported excessive sweating (36.5%), burning/stinging/itching of eyes
      (35.7%), dry/sore throat (25.5%), and excessive salivation (14.1%), all more
      prevalent among sprayers. Among men, excessive sweating and eye and throat
      problems were significantly associated with exposure. There is a need to raise
      farmers' and authorities' awareness of the need to use protective gear when
      handling pesticides.

PMID- 16967830
TI  - Cancer incidence and mortality in the industrial city of Sumgayit, Azerbaijan.
AB  - This study, the first environmental cancer study in Azerbaijan, addressed
      concerns that residents of the industrial city of Sumgayit have an increased
      cancer burden as a consequence of intense occupational and environmental
      pollution from industry. Vital statistics data were used to calculate annual
      crude cancer incidence and mortality rates for selected cancers and regions in
      Azerbaijan for the years 1980-2000. Poisson regression analysis of age- and sex
      specific data from 1995-2000 demonstrates an increased risk for selected cancers
      in Sumgayit relative to the rest of the country, as measured by adjusted rate
      ratios [aRR (95% CI))]: larynx 1.39 (1.04, 1.85), lung 1.67 (1.44, 1.92), bladder
      2.49 (1.93, 3.22), and all sites 1.51 (1.43, 1.58). Sumgayit appears to suffer
      from an increased cancer burden; poor data quality and suspected underreporting,
      however, prevent accurate estimates of incidence or mortality rates. Construction
      of a modern cancer registry would be prerequisite to more detailed examinations
      of cancer rates in the country.

PMID- 16967831
TI  - Development of permissible exposure limits: the California experience.
AB  - The California OSHA Airborne Contaminant Advisory Committee reviewed several
      hundred substances and recommended occupational exposure limits with the intent
      of worker and employer protection. The model used offers important benefits.
      First, by allowing open meetings, the process was transparent, and input could be
      offered by concerned stakeholders. Second, the process was data-driven and,
      therefore, less susceptible to bias and error. Third, by incorporating members
      with backgrounds in toxicology, epidemiology, risk assessment, occupational
      medicine, and industrial hygiene, the process fostered a thorough and diverse
      assessment of substances.

PMID- 16967832
TI  - Banning asbestos in Asia: campaigns and strategies by the Asian Network for the
      Rights of Occupational Accident Victims (ANROAV).
AB  - China, India, Indonesia, and Thailand are among the largest consumers of
      asbestos. Because markets in the West are dwindling, asbestos is heavily promoted
      in Asia. In spite of widespread usage, asbestos-related diseases are surprisingly
      few and reported cases of mesothelioma are rare in Asia except in Japan, Korea,
      and Singapore. The problem lies in diagnosis. Most of the asbestos-related
      diseases are not diagnosed in Asia and thus do not appear in government
      statistics. This deadly substance is killing workers. Unless drastic action is
      taken to stop its use, Asian workers as well as the general population will pay a
      heavy price.

PMID- 16967833
TI  - FIOH-sponsored newsletter misrepresents asbestos hazards in Zimbabwe.
AB  - The Finnish Institute of Occupational Health (FIOH) has received support from the
      World Health Organization (WHO) and the International Labor Office (ILO) to
      publish the African Newsletter on Occupational Health and Safety. The African
      Newsletter on Occupational Health and Safety should not be a medium for industry
      propaganda, or the source of misinformation among the workers of Africa. Instead,
      FIOH should provide the same level of scientific information in Africa that it
      does in Finland and other developed countries.

PMID- 16967834
TI  - European Union bans atrazine, while the United States negotiates continued use.
AB  - Atrazine is a common agricultural herbicide with endocrine disruptor activity.
      There is evidence that it interferes with reproduction and development, and may
      cause cancer. Although the U.S. Environmental Protection Agency (EPA) approved
      its continued use in October 2003, that same month the European Union (EU)
      announced a ban of atrazine because of ubiquitous and unpreventable water
      contamination. The authors reviewed regulatory procedures and government
      documents, and report efforts by the manufacturer of atrazine, Syngenta, to
      influence the U.S. atrazine assessment, by submitting flawed scientific data as
      evidence of no harm, and by meeting repeatedly and privately with EPA to
      negotiate the government's regulatory approach. Many of the details of these
      negotiations continue to be withheld from the public, despite EPA regulations and
      federal open-government laws that require such decisions to be made in the open.

PMID- 16967835
TI  - The past suppression of industry knowledge of the toxicity of benzene to humans
      and potential bias in future benzene research.
AB  - Petrochemical industry representatives often withhold information and
      misinterpret positive evidence of toxicity of benzene, even from their own
      research, also discouraging or delaying disclosure of findings of adverse effects
      to the public. They now appear to be attempting to influence study results in
      industry's favor by offering predetermined conclusions about study results as
      part of an effort to draw financial support for the studies. The American
      Petroleum Institute is currently raising funds for benzene research being
      conducted in China for which it has already announced the intended conclusions.

PMID- 16967836
TI  - Emerging issues in occupational safety and health.
AB  - In developed countries, changes in the nature of work and the workforce may
      necessitate recalibrating the vision of occupational safety and health (OSH)
      researchers, practitioners, and policymakers to increase the focus on the most
      important issues. New methods of organizing the workplace, extensive labor
      contracting, expansion of service and knowledge sectors, increase in small
      business, aging and immigrant workers, and the continued existence of traditional
      hazards in high-risk sectors such as construction, mining, agriculture, health
      care, and transportation support the need to address: 1) broader consideration of
      the role and impact of work, 2) relationship between work and psychological
      dysfunction, 3) increased surveillance basis for research and intervention, 4)
      overcoming barriers to the conduct and use of epidemiologic research, 5)
      information and knowledge transfer and application, 6) economic issues in
      prevention, and 7) the global interconnectedness of OSH. These issues are offered
      to spur thinking as new national research agendas for OSH are considered for
      developed countries.

PMID- 16967837
TI  - Occupational health care for the 21st century: from health at work to workers'
      health.
AB  - A survey of relevant national and international legislation and recommendations
      on occupational health (OH) organization revealed two fundamental approaches to
      OH: 1) the historically older labor approach, essentially seeing OH care as an
      obligation of the employer derived from the labor contract, and 2) an emerging
      health approach, including all workers and all aspects of health, A draft decree
      on OH in Flanders seeks to integrate the two approaches. It extends the scope of
      OH to all workers (not only employees), introduces holistic health surveillance,
      rejects the incapacity concept, provides for strong integration of health and
      workplace surveillance, and stresses ethics. Workers' satisfaction is seen as the
      first criterion in quality control. Systematic data collection and analysis, and
      when necessary, scientific research are recommended. Additional resources for OH
      services should be provided by stakeholders other than employers.

PMID- 16967838
TI  - Don't ask, don't tell? Preventing information exchange increases the risks of
      chemical exposures.

PMID- 16967839
TI  - Poultry workers shouldn't serve as canaries.

PMID- 16967840
TI  - Scientific method questioned.

PMID- 16967841
TI  - Differential peeky bias.

PMID- 16967842
TI  - Training and public health hit for pounds 350m to recover deficits.

PMID- 16967843
TI  - Spent forces: who pulls the levers on local funding.

PMID- 16967844
TI  - On a summer of discontent.

PMID- 16967845
TI  - Acute trusts July 2006.

PMID- 16967846
TI  - Rocky patch.
AB  - As PCTs come under intense financial pressure, it is often local authority
      partners who feel the burden. Councils are being asked to fund cases that would
      previously have been an NHS responsibility and have seen health partners pull out
      of joint projects. instead of legal action and 'tit-for-tat arguments' the best
      solution is more forward planning; new PCT boundaries should help.

PMID- 16967847
TI  - Mental health. Working method.

PMID- 16967848
TI  - Only a third of chief executive hopefuls win new PCT jobs.

PMID- 16967849
TI  - Sir Liam's damning verdict heralds new dawn of regulation.

PMID- 16967850
TI  - On challenging acute trusts.

PMID- 16967851
TI  - Why binning bad habits will take the fudge out of finance.

PMID- 16967852
TI  - Variations in length of stay.

PMID- 16967853
TI  - Refer to sender.
AB  - GP scepticism about demand management has been successfully tackled by a co
      operative venture involving GPs and a primary care trust. Using the choose and
      book system to manage referrals makes it easy for data to be collected and
      analysed.

PMID- 16967854
TI  - On public health.

PMID- 16967855
TI  - The anatomy of learning.

PMID- 16967856
TI  - How community health care saves lives.

PMID- 16967857
TI  - Building healthy communities.
AB  - Open Door Health Center's community health plan enables it to increase access to
      an integrated array of health, social, and mental health/substance abuse
      services. This plan is divided into life cycle segments. Chronic disease
      treatment and management are built into each segment as appropriate. This plan
      for the underinsured and uninsured takes a proactive approach to preventive care
      and includes health education and promotion in all of its services. Consistent
      with our mission and the needs of our patient population is a strong emphasis on
      culturally and linguistically appropriate services. Our commitment to health
      education and empowerment to help clients manage their health and related issues
      are having an impact on the health of the community.

PMID- 16967858
TI  - Innovation fosters community health.

PMID- 16967859
TI  - Wanda Alexander builds bridges to better care. Interview by Laura Rydholm.

PMID- 16967860
TI  - Documenting the value of faith community nursing: 1. Saving hundreds, making
      cents--A study of current realities.

PMID- 16967861
TI  - Documenting the value of faith community nursing: 2. Faith nursing online.

PMID- 16967862
TI  - Community-based mental health care. Interview by Susan Lampe.

PMID- 16967863
TI  - [Physiology of innate immunity].
AB  - The mechanisms of innate immunity functioning--the first row of counteraction
      (resistance) to infectious agents are reviewed. A concept of pathogen associated
      molecular patterns--the unique prokaryotic conservative structures--as well as a
      concept of pattern-recognizing receptors of innate immunity cell recognizing the
      given bacterial patterns, are discussed. The data on molecular and genetic
      structures of both Toll-like- and NOD-receptors: the important compounds of
      pattern-recognizing receptors, the main signaling pathways from receptor to cell
      genome activation as well as the principles of immune cell activation by pathogen
      associated molecular patterns are submitted.

PMID- 16967864
TI  - [The physiological activation and inhibition features of immunity cell functions.
      Receptor structures and intracellular signal ways of macrophages and natural
      killer cells].
AB  - The receptor structures of activating and inhibiting types of innate immunity
      central cells (macrophages and natural killer cells) participating in supporting
      genetic homeostasis and providing organism protection from extracellular and
      intracellular microbes and other alien cells, have been considered. The molecular
      physiological formation mechanisms of intracellular signal ways providing
      macrophage activation under interaction influence of Toll-like phagocyte
      receptors with one of its ligands: lipopolysaccharide that is the main component
      of gram-negative bacterium membrane have been analysed.

PMID- 16967865
TI  - [Structure and functions of the brain orexin-containing neurons].
AB  - The results of investigations of the new discovered brain orexin neurons, their
      chemical structure, localization and functions are reviewed. The following data
      are described: the specifics of orexins mRNA, orexins A and B and their
      receptors; connections between orexin neurons and neurons from different
      structures of the brain and spinal cord and the participation of the orexin
      neuron system in the functional regulation.

PMID- 16967866
TI  - [Blocks of neuron correlates of behaviour in the monkey brain prefrontal cortex
      and striatum].
AB  - The dynamics of tonic neuron activity of the putamen and prefrontal cortex of
      monkey's brain is researched by studying sequential stages of executive behavior
      program. It is determined that tonic responses in both structures are classified
      in separate blocks. The blocks are timed to key moments of behavior connected
      with intermediate goals framed by a common task. As to the structures of the
      aforesaid blocks of tonic activity in cortex and striatum, they are different in
      instructive part of the program and similar in executive one. More differential
      attitude of cortex is revealed to the sequence of executive behavior activity.

PMID- 16967867
TI  - [NO-synthase dependent increase in citrulline extracellular level in the nucleus
      accumbens during acquisition and expression of conditioned emotional response].
AB  - In Sprague-Dawley rats, by means of in vivo microdialysis combined with HPLC
      analysis, it was shown that acquisition and expression of conditioned emotional
      response resulted in increase in extracellular level of citrulline: a nitric
      oxide co-product, in the nucleus accumbens. The rise extracellular citrulline
      caused by the acquisition of the response was significantly reduced by
      intraaccumbens infusion of 7-nitroindasole (0.5 mM), a selective inhibitor of
      neuronal NO-synthase, and completely prevented by intraaccumbens infusion of N
      nitroarginine (0.5 mM): a nonselective NO-synthase inhibitor. The increase in
      citrulline extracellular level cased by expression of the conditioned emotional
      response is completely prevented by infusion of both NO-synthase inhibitors. The
      data obtained suggest that the acquisition and the expression of the conditioned
      emotional response increase the production of nitric oxide in the n. accumbens,
      predominantly due to activation of the neuronal NO-synthase.

PMID- 16967868
TI  - [Interhemisphere differences of extrastriate cortical activation during attention
      and selection of lateralized visual stimuli in humans].
AB  - The cortical activation was estimated by event-related potentials (ERPs) methods
      during selection tasks of lateralized visual stimuli in right and left hemi
      fields requiring different forms of attention: 1. Attention of a stimuli form, 2.
      Attention of a stimuli position, 3. Combined attention of form and position. ERPs
      were recorded in 15 young healthy adults in 6 leads: P3, P4, T3, T4, T5, T6 and
      endogenous ERPs components: CNV (contingent negative variation), N1, P3 and
      complex [N1--P3]. The differences between ERPs at contra- and ipsilateral stimuli
      in the right and left hemispheres were considered as indices of asymmetry. The
      asymmetry was revealed in right hemisphere in all kinds of attention forms. The
      level (amplitude) of right-side asymmetry was depended on the level of attention:
      The significant relation between the right-side asymmetry and subjects' reaction
      time was also revealed. It is proposed that such an asymmetry is the evidence of
      better spatial differentiation of visual stimuli in right hemisphere in humans.

PMID- 16967869
TI  - [Magnesium ions prevent development of hyperkinesis produced by picrotoxin
      intrastriatal microinjections into the rat neostriatum].
AB  - The effects of daily bilateral microinjections of GABA-A receptor antagonist
      picrotoxin (2 mcg) into rostral neostriatum of the rats in chronic experiments
      were investigated. The picrotoxin was injected in volume of 1 mcl of saline or in
      1 mcl of 1.0 M or 1.5 M MgCl2 solution; 1 mcl of saline or 1.0 M MgCl2 solution
      were injected in control groups of animals. The impairment of the avoidance
      conditioning in shuttle box, changes in free locomotor activity and the
      stereotypic choreo-myoclonic limb jerks were registered in rats with picrotoxin
      with the saline microinjections. The motor deviation registered are similar with
      Huntington chorea hyperkinesis in humans. The addition of magnesium ions into
      injected solution prevented both the lyperkinesis and condition behaviour
      realization impairment. As the magnesium is a universal calcium channel blocker,
      the calcium homeostasis of striatal neurons impairment as one of principal
      elements of hyperkinesis pathogenesis is proposed.

PMID- 16967870
TI  - [Protective effect of peptide semax the rat heart in acute myocardial
      infarction].
AB  - Semax, a member of ACTH-derived peptides family, has been employed in the
      treatment of acute ischemic stroke in patients. It decreased neurological deficit
      and reduced NO hyperproduction in the rat brain, caused by acute cerebral
      hypoperfusion. We suggested that semax is also able to protect rat heart from
      ischemic damage in acute myocardial infaction (AMI). AMI was induced by left
      coronary artery occlusion, myocardial ischemic area averaged 30 % of left
      ventricle. In 2 hours after coronary occlusion, the AMI group developed 11 %
      reduced mean arterial blood pressure and 48 % increased diastolic blood pressure
      in left ventricle in comparison with sham-operated control group. However,
      infusion of either dobutamine, which directly stimulates myocardial
      contractility, or sodium nitroprusside and phenylephrine, that change vascular
      resistance and thus cardiac afterload, did not reveal distinctions in hemodynamic
      parameters between groups. These data indicate absense or only moderate cardiac
      dysfunction in rats with AMI and are consistent wih morphometrical and
      histochemical studies that did not detect any necrotic or apoptotic (TUNEL-test)
      changes in left ventricular cardiomyocytes in spite of development of distinct
      ischemic disturbances of mitochondria and nuclear in about 50 % of cardiomyocytes
      in 2 hours after AMI. Semax (150 microg/kg), given i. p. 15 min and 2 hours after
      coronary occlusion, caused no effect on cardiac function, but completely
      prevented ischemia-induced ultrastructural changes of cardiomyocytes. This
      protective effect was accompanied by the ability of peptide to blunt the increase
      in plasma concentrations of nitrates, observed in AMI group.

PMID- 16967871
TI  - [Mechanisms of disrupting the microcirculation in the brain during deep
      hypothermia development].
AB  - The number of the acts of leukocyte adhesion per unit of the vessel length was
      shown to increase gradually in the venous brain vessels during gradual cooling of
      the white rat from the body temperature in the rectum of approximately 37 to 13.5
      +/- 0.2 degrees C. Upon a very deep hypothermia at the level of body temperature
      of 15 degrees C, the adhesion ofleukocytes to the walls of the brain microvessels
      gains a mass character. As the body temperature decreases to 13.5 +/- 0.2 degrees
      C, the respiration gets arrested. This coincides with an aspecially abrupt
      increase in the number of the acts of adhesion and with stretching the venules
      and smallest veins. The dynamics of these phenomena resembles the development of
      the mass adhesion of leukocytes during various kinds of hypoxia. There are
      reasons to believe that the adhesion of leukosytes during hypothermia disrupts
      the microcirculation and provokes the development of hypoxia in the cooled brain.

PMID- 16967872
TI  - [The effect of neonatal administration of monosodium glutamate on behavior and
      blood corticosterone level].
AB  - DBA/2 male mice were treated with monosodium glutamate (MSG) in a dose of 4 mg/g
      on 1, 3, 5, 7, 9 days after birth. Saline treated and intact males were used as
      control groups. MSG treated males displayed decreased number of crossed squares,
      rearings, entries in the centre and time in the centre of open field in
      comparison with saline-treated but not intact animals. Time in the light
      compartment of the light-dark box was increased in MSG-treated mice versus both
      saline treated and intact animals. MSG administration reduced acoustic startle
      response but did not affect the magnitude of prepulse inhibition of the startle
      reflex. Sexual motivation in male mice was reduced by MSG, the same trend was
      observed after saline treatment. MSG administration increased corticosterone
      basal level 4-fold while saline treatment did not affect it. These data suggest
      that neonatal administration of MSG decreases locomotion, exploratory activity,
      anxiety in male mice, while corticosterone level is increased. Saline treatment
      increases these parameters (except sexual motivation), and this augmentation is
      not connected to changes in corticosterone basal level.

PMID- 16967873
TI  - [Mechanism of carbachol and adenosine action on spontaneous quantal mediator
      release at frog neuromuscular junction].
AB  - Experiments on the frog sartorius muscle showed that nonhydrolisable
      acetylcholine analog carbachol (CCh) depresses spontaneous quantal mediator
      release via muscarinic M2 receptors of nerve ending. Adenosine (Ade) acting via
      inhibitory A1 receptors is another strong spontaneous quantal release modulator.
      Inhibition of pertussis toxin (PTx)-sensitive G-proteins only partly eliminated
      CCh and Ade depressive action. It means metabotropic A1 and M2 receptors of the
      frog nerve ending regulate spontaneous quantal release via activating of both PTx
      sensitive and PTx-insensitive inhibitory mechanisms.

PMID- 16967874
TI  - Game planning.

PMID- 16967875
TI  - Upshifting physicians who haven't slowed down in retirement.

PMID- 16967876
TI  - Work group tackles sick tax.

PMID- 16967877
TI  - MMA looks at early retirement health insurance options.

PMID- 16967878
TI  - MMA supports Gov. Pawlenty's call for study of drug-marketing costs.

PMID- 16967879
TI  - Practice doesn't make perfect.

PMID- 16967880
TI  - Retire...or not?

PMID- 16967881
TI  - The graying of a physician.

PMID- 16967882
TI  - What will I do without you?

PMID- 16967883
TI  - Don't overestimate yourself.

PMID- 16967884
TI  - Use of the emergency department by Somali immigrants and refugees.
AB  - Staff at a hospital emergency department (ED) located in an urban neighborhood
      densely populated by Somali immigrants and refugees have observed that a large
      number of Somali patients use the ED for care that is normally provided in a
      clinic setting. This article reports on the Somali population's use of the ED for
      such care. It also explores Somali traditions and culture in order to shed light
      on this population's health care practices and attitudes toward the medical
      system in this country, and it makes recommendations consistent with those
      findings for more effectively meeting the health needs of Somalis.

PMID- 16967885
TI  - The doctor's husband.

PMID- 16967886
TI  - A voice from an ancient stump.

PMID- 16967887
TI  - The oldies are goodies.

PMID- 16967888
TI  - Nurse managers as transformational and transactional leaders.
AB  - Nurse managers demonstrating transformational leadership are more likely than
      transactional leaders to have committed staff nurse followers. Committed
      followers exert extra effort, thus improving unit performance and enhancing the
      organization's competitive advantage.

PMID- 16967889
TI  - Hardiness, stress, and use of ill-time among nurse managers: is there a
      connection?
AB  - Intense job-related demands often result in effects on job performance and
      increased use of ill-time. In this study, associations between hardiness, stress,
      and use of ill-time among nurse managers were examined. High-hardy/low-stress
      managers used 27% less ill-time than those low-hardy/high-stressed.

PMID- 16967890
TI  - Stress and coping in nurse managers: two decades of research.
AB  - An integrative literature review was undertaken to examine the research related
      to stress and coping in nurse managers. Key gaps in the literature were
      identified with implications for research presented.

PMID- 16967892
TI  - Paving and resurfacing the road to Magnet: Part III--unique organizational
      characteristics.

PMID- 16967891
TI  - Insurer policies create barriers to health care access and consumer choice.
AB  - A national survey shows that most insurance companies refuse to credential nurse
      practitioners in nurse-managed health centers as primary care providers. These
      prohibitive policies along with weak federal and state laws threaten the long
      term sustainability of nurse-managed health centers as safety net health care
      providers, and the ability for nurse practitioners to become an accepted primary
      health care source in the United States.

PMID- 16967893
TI  - The art of truth telling: handling failure with disclosure and apology.
AB  - There are sentinel events and near misses associated with leadership and
      management, as well as the clinical process of health care. We should hold
      ourselves accountable to the same level of rigor and analysis of these events and
      near misses as we expect from clinicians. Research and analysis will continue to
      help us understand the science behind the power of truth telling and apology.

PMID- 16967894
TI  - Human capital management: Implications for health care leaders.

PMID- 16967895
TI  - Still in recovery. One year after Hurricane Katrina hit the Gulf Coast, many New
      Orleans hospitals are still struggling to restore services.

PMID- 16967896
TI  - It's a seller's market. Big Three's sales aren't enough to flood market.

PMID- 16967897
TI  - Leaving on a high note. AHA is flush as its president exits at the top of the
      heap in compensation.

PMID- 16967898
TI  - Uniting to conquer. SEIU joins with other unions to target healthcare workers as
      organizing intensifies.

PMID- 16967899
TI  - New Orleans needs intensive care. The area's healthcare system has been slighted
      in federal recovery effort.

PMID- 16967900
TI  - On the same page. Patient-created Web sites keep family, friends informed, but
      for hospitals the pages carry risks as well as rewards.

PMID- 16967901
TI  - 1/f correlations in viral genomes--a Fast-Fourier Transformation (FFT) Study.
AB  - We have studied the presence of long-range correlations in the complete genomes
      of ten different dsDNA viruses and Saccharomyces cerevisiae (bakers' yeast)
      chromosome I. We have also studied the correlation between the distribution of
      the gene length and the domain of "1/f region" of their genomes. Linear
      regression analysis was done for the power-law region of these organisms and the
      slope values obtained were approximately -1, which signify the existence of "1/f
      noise" in the low and medium (intermediate) frequency regions. This suggests the
      presence of long-range correlations in their genomes. The presence of 1/f noise
      in a given frequency interval indicates the existence of a fractal (self-similar)
      structure in the corresponding range of wavelengths. The results of our study
      suggest that genes have correlations within themselves, and the correlations
      appear to be related with the scaling exponent alpha.

PMID- 16967902
TI  - Regulation of MAL1+ gene expression encoding maltase in Schizosaccharomyces pombe
      by added inositol.
AB  - In this study, the effects of inositol addition on maltase activity and
      expression of MAL1+ gene encoding maltase in Schizosaccharomyces pombe were
      investigated. The maximum specific maltase activity was observed, when the
      concentration of inositol reached 6.0 microg/ml in the synthetic medium
      containing 2.0% glucose. At 1.0 microg/ml inositol concentration, the maltase
      activity continuously decreased, as initial glucose concentration was higher than
      0.1%. mRNA encoding maltase and phosphatidylinositol (PI) content were higher in
      the cells grown in the synthetic medium with 6.0 microg/ml of inositol and 2.0%
      glucose than those with 1.0 microg/ml of inositol. These results demonstrated
      that higher inositol concentration in the synthetic medium could derepress MAL1+
      gene expression in S. pombe and PI might be involved in derepression of MAL1+
      gene expression in S. pombe probably by PI-type signalling pathway.

PMID- 16967903
TI  - Effect of denaturants on the structure and activity of 3-hydroxybenzoate-6
      hydroxylase.
AB  - The effect of denaturants such as urea, sodium dodecylsulphate (SDS), guanidinium
      hydrochloride (Gu.HCl) on the structure of enzyme 3-hydroxybenzoate-6-hydroxylase
      was studied using intrinsic fluorescence and far and near-UV-CD spectroscopic
      techniques. Also, activity profiles of the enzyme, as a function of increasing
      concentrations of denaturants were studied. The far-UV CD spectrum of the enzyme
      did not show appreciable alterations in the presence of urea, SDS or Gu.HCl,
      thereby suggesting that the protein does not undergo gross conformational changes
      in its alpha-helical secondary structure. The treatment of enzyme with 2 M urea
      resulted in almost complete loss of catalytic activity, accompanied by the
      reduction of emission fluorescence of enzyme. Similarly, treatment with 0.01% SDS
      also caused almost complete loss of activity and quenching of enzyme fluorescence
      as well as a red shift in the emission peak. In addition, reduction in the
      intensity of near-UV-CD spectrum, especially at 280 nm was observed. About 70% of
      the activity was lost by treatment with 20 mM Gu.HCl, accompanied by quenching of
      intrinsic fluorescence of the enzyme. The change in intrinsic fluorescence of the
      enzyme in the presence of 5 mM-100 mM Gu.HCI could be correlated to progressive
      loss of catalytic activity. Thus, intrinsic fluorescence (due to tryptophan
      residues) could be used as an effective probe to provide an insight into the
      relation between the activity and subtle conformational changes of the enzyme.
      The results suggested that denaturants caused very slight conformational changes
      in the enzyme that perturbed the microenvironment of aromatic amino acid residues
      such as tryptophan accompanied by reduction or loss of catalytic activity.

PMID- 16967904
TI  - Quantitative structure-activity relationship (QSAR) analysis of a series of
      indole analogues as inhibitor for human group V secretory phospholipase A2.
AB  - Phospholipase A2s (PLA2) are a class of enzymes, which catalyze the hydrolysis of
      membrane phospholipids at the sn-2 position to release fatty acids and
      lysophospholipids. When the fatty acid is arachidonic acid (AA), a complementary
      metabolism leads to pro-inflammatory mediators collectively known as eicosanoids.
      Thus, inhibiting PLA2 activity remains a prime target for the development of new
      drugs for the treatment of inflammation-related diseases. More than one type of
      PLA2s plays a major role in inflammatory disease conditions. In the present
      study, quantitative structure-activity relationship (QSAR) study was performed
      for a series of 48 Me-indoxam derivatives as human group V PLA, (hVPLA2)
      inhibitors, using molecular operating environment (MOE) software. The hVPLA2 is a
      secretory PLA2 (sPLA2), involved in eicosanoid formation in inflammatory cells
      such as macrophages and mast cells. These studies have come out with three good
      predictive models (r = 0.82-0.84), which are cross-validated (rcv = 0.68-0.70) by
      leave-out-one method (Loo). The positive correlation of spatial descriptor Pmiz
      with inhibitory activity shows that proper orientation of the substitution at R
      position towards Z-axis is necessary to facilitate the possible interactions of
      the indole core with active site residues of the PLA2 enzyme. The negative
      contribution of b_rotN (atom and bond count-type descriptor) suggests that
      increasing flexibility conferred by the R substitution is detrimental for the
      activity. In addition to the hVPLA2 inhibitory activity is found to be highly
      influenced by molecular size, energy and polarity of the Me-indoxam derivatives.

PMID- 16967905
TI  - Metabolic and physiologic characteristics of skeletal muscle determine its
      response to clenbuterol treatment.
AB  - beta-Adrenoceptor agonists are reported to induce skeletal muscle hypertrophy and
      hence serve as valuable adjunct to the treatment of wasting disorders. In the
      present study, we attempted to find out whether metabolic and physiologic
      characteristics of fibres are important in determining skeletal muscle response
      to clenbuterol (an adrenergic receptor agonist) therapy, as proposed in the
      treatment of wasting disorders. The treatment of mice with clenbuterol (2 mg/kg
      body wt for 30 days) resulted in skeletal muscle hypertrophy, more common amongst
      fast-twitch glycolytic fibres/muscle, with increase in body mass and a parallel
      rise in muscle mass to body mass ratio. Measurement of fibre diameters in soleus
      (rich in slow-twitch oxidative fibres), ALD or anterior latissimus dorsi (with a
      predominance of fast-twitch glycolytic fibres) and gastrocnemius (a mixed-type of
      muscle) from clenbuterol-treated mice for 30 days revealed noticeable increase in
      the per cent population of narrow slow-twitch fibre and a corresponding decline
      in white-type or fast-twitch glycolytic fibres in gastrocnemius and ALD. As
      revealed by counting of muscle cells in soleus, narrow red fibres declined with
      corresponding increase in white-type glycolytic fibres population. A significant
      decline in the succinic dehydrogenase activity was observed, thereby suggesting
      abnormality in oxidative activity of skeletal muscles in response to clenbuterol
      therapy.

PMID- 16967906
TI  - Augmented bone-matrix formation and osteogenesis under magnetic field stimulation
      in vivo XRD, TEM and SEM investigations.
AB  - Bone is a composite biomaterial, which is formed, when proteins constituting
      collagen fibers attract calcium, phosphate and hydroxide ions in solution to
      nucleate atop the fibers. It grows into a hard structure of tiny crystallites of
      hydroxyapatite, aligned along the long axis of collagen fibers. The present work
      reports the stimulating effect of static magnetic field on microstructure and
      mineralization process of bone repair. A unilateral transverse fracture of mid
      shaft of metacarpal was surgically created in healthy goats under thiopental
      sedation and xylocaine analgesia. Two bar magnets (approximately 800 gauss/cm2
      field strength) were placed across the fracture line at opposite pole alignment
      immobilized in Plaster of Paris (POP) splint bandage for static magnetic field
      stimulation. Radiographs were taken at weekly intervals up to 45 days. Results
      show that formation of extra-cellular matrix and its microstructure can be
      influenced by non-invasive physical stimulus (magnetic field) for achieving an
      enhanced osteogenesis, leading to quicker regeneration of bone tissue in goats. X
      ray diffraction (XRD) patterns of treated (magnetic field-exposed) and control
      samples revealed the presence and orientation of crystalline structures.
      Intensity of diffraction peaks corresponding to 310 and 222 planes were enhanced
      with respect to 211 families of reflections, indicating preferential alignment of
      the crystals. Also, the percent crystallinity and crystal size were increased in
      treated samples. The study provides a biophysical basis for augmented fracture
      healing under the influence of semi-aligned static magnetic field applied across
      the fracture line.

PMID- 16967907
TI  - Vibrational dynamics of morphine in relation to Leu5--and Met5-enkephalins.
AB  - A complete normal coordinate analysis of morphine using Wilson's GF matrix method
      and Urey Bradley force field has been carried out to understand the dynamical
      behaviour of morphine in relation to Leu5- and Met5-enkephalins. In addition,
      charge distribution on different atoms of morphine, along with that of Leu5- and
      Met5-enkephalins using CNDO/2 method is also reported. The similarity in charge
      distribution on some of the sites of these molecules is indicative of the
      possible interactions at the same receptor site. It is surmised that the
      recognition and interaction of active sites with the receptor must be dynamical
      in nature and for this the modes involving the active sites should play an
      important role. It is found that the binding to receptors is not static, but a
      dynamic process.

PMID- 16967908
TI  - Bemnisia tabaci feeding induces pathogenesis-related proteins in cassava (Manihot
      esculenta Crantz).
AB  - Cassava (Manihot esculenta Cranzts) plants fed upon by whitefly Bemisia tabaci
      showed increased levels of pathogenesis-related (PR) proteins, such as beta-1, 3
      glucanase, peroxidase and chitinase activities, as compared to uninfested plants.
      The enzymes increased in specific activities from 2 to 7 fold and protein content
      in leaf extracts decreased in whitefly-infested plants, compared to uninfested
      plants. Among the three PR proteins, B. tabaci feeding induced significantly
      higher beta-1, 3-glucanase activities, when compared with other two PR proteins.
      Study also discussed the possible application of PR proteins in whitefly control
      program.

PMID- 16967909
TI  - Biophysical studies on the liposome-albumin system.
AB  - The potential use of liposomes as a delivery system is still limited by the poor
      understanding of their interaction mechanisms with biological media. In the
      present work, interaction between bovine albumin (BA) and liposomes was studied
      using phase transition and dielectric measurements as well as solubilization
      process using non-ionic detergent octylglucoside (OG). After liposomes were
      incubated with diluted and concentrated BA, phase transition, characterizing the
      liposome membrane exhibited a shift towards higher temperatures, together with
      initiation of multiple phase transitions. The relaxation time of liposome
      membrane molecules also increased in a concentration-dependent manner. The
      solubilization profiles of incubated samples also showed remarkable changes,
      especially in beginning of solubilization stages. Moreover, amount of detergent
      needed to completely solubilize membrane was also increased. It was concluded
      that BA significantly altered the physical state of liposome membrane, which may
      be attributed to BA interaction with liposomes surface and/or by its
      incorporation within the bilayer membrane.

PMID- 16967910
TI  - TRendys meeting report 2005.

PMID- 16967911
TI  - Strategies for fostering HPV vaccine acceptance.
AB  - Vaccines that protect against infection with the types of human papillomavirus
      (HPV) commonly associated with cervical cancer (HPV 16 and 18) and genital warts
      (HPV 6 and 11) are expected to become available in the near future. Because HPV
      vaccines are prophylactic, they must be administered prior to exposure to the
      virus, ideally during preadolescence or adolescence. The young age of the target
      vaccination population means that physicians, parents, and patients will all be
      involved in the decision-making process. Research has shown that parents and
      patients are more likely to accept a vaccine if it is efficacious, safe,
      reasonably priced, and recommended by a physician. Widespread education of
      physicians, patients, and parents about the risks and consequences of HPV
      infection and the benefits of vaccination will be instrumental for fostering
      vaccine acceptance.

PMID- 16967912
TI  - Epidemiology and natural history of human papillomavirus infections in the female
      genital tract.
AB  - Human papillomavirus (HPV) is the most common newly diagnosed sexually
      transmitted infection in the United States. Although the majority of sexually
      active adults will be infected with HPV at least once in their lives, it is
      sexually active women less than 25 years of age who consistently have the highest
      rates of infection. Besides youth and gender, common risk factors for HPV
      infection and clinical sequelae of infection include high number of sexual
      partners and coinfection with Chlamydia trachomatis or herpes simplex virus. Most
      HPV infections are cleared by the immune system and do not result in clinical
      complications. Clinical sequelae in cases of low-risk HPV infection consist of
      genital warts, and clinical manifestations of high-risk HPV infection include
      abnormal Pap test results, low-grade squamous intraepithelial lesions (LSIL),
      high-grade squamous intraepithelial lesions (HSIL), and cervical cancer. LSIL,
      HSIL, and cervical cancer carry significant morbidity and/or mortality; genital
      warts and abnormal Pap test results are often significant sources of psychosocial
      distress. Currently, there are neither effective means of preventing HPV
      transmission nor cures for clinical manifestations: infection can only be
      prevented via complete sexual abstinence, while treatment for clinical sequelae
      such as genital warts and cytologic abnormalities consists of removing the
      problematic cells and watching for recurrence; this method consumes significant
      health care resources and is costly. New prophylactic HPV vaccines promise to
      dramatically reduce the incidence of HPV infection, genital warts, and cytologic
      abnormalities.

PMID- 16967913
TI  - Reducing the health burden of HPV infection through vaccination.
AB  - Human papillomavirus (HPV), a sexually transmitted infection and the etiologic
      cause of genital warts and cervical cancer, is highly prevalent in sexually
      active men and women. Although cervical screening procedures have significantly
      reduced the disease burden associated with HPV infection, they are expensive and
      abnormal results cause significant emotional distress. Therefore, prevention may
      be an effective strategy for reducing the economic, psychosocial, and disease
      burden of HPV infection. Multivalent vaccines are now in clinical development. A
      bivalent vaccine that protects against HPV 16 and 18, and a quadrivalent vaccine
      which protects against HPV types 6, 11, 16, and 18, have been shown to
      significantly reduce the occurrence of incident and persistent HPV infections in
      phase 2 clinical trials; phase 3 trials are currently underway. HPV vaccines will
      be most effective when administered prior to initiation of sexual activity, and
      vaccination campaigns should aggressively target preadolescent and adolescent
      populations.

PMID- 16967914
TI  - Target-related applications of first principles quantum chemical methods in drug
      design.

PMID- 16967915
TI  - Reversible coordinative bonds in molecular recognition.

PMID- 16967916
TI  - C(2)-symmetric chiral bis(oxazoline) ligands in asymmetric catalysis.

PMID- 16967917
TI  - Dynamic combinatorial chemistry.

PMID- 16967918
TI  - Peptide conjugates of oligonucleotides: synthesis and applications.

PMID- 16967919
TI  - Spider silk: ancient ideas for new biomaterials.

PMID- 16967920
TI  - Detecting RNA and DNA with templated chemical reactions.

PMID- 16967921
TI  - Advances in the synthesis and catalytic applications of organosulfonic
      functionalized mesostructured materials.

PMID- 16967922
TI  - Organometallic hydroxides of transition elements.

PMID- 16967923
TI  - Kinetics, spectroscopy, and computational chemistry of arylnitrenes.

PMID- 16967925
TI  - Use of iodocompounds in radical polymerization.

PMID- 16967924
TI  - Fluorinated phosphonates: synthesis and biomedical application.

PMID- 16967926
TI  - Polycyclic polyprenylated acylphloroglucinols.

PMID- 16967927
TI  - Chiral salen complexes: an overview to recoverable and reusable homogeneous and
      heterogeneous catalysts.

PMID- 16967928
TI  - Synthesis of transportation fuels from biomass: chemistry, catalysts, and
      engineering.

PMID- 16967929
TI  - The nose as a stereochemist. Enantiomers and odor.

PMID- 16967930
TI  - X-ray magnetic circular dichroism of size-selected, thiolated gold clusters.
AB  - We report herein the X-ray magnetic circular dichroism (XMCD) at the Au L2,3
      edges of a series of Au clusters protected by glutathione (GSH). The samples used
      here included AuN(SG)M with (N, M) = (10, 10), (15, 13), (18, 14), (22, 16), (25,
      18), (29, 20), (39, 24) and a sodium gold(I) thiomalate (SGT) as a reference.
      Magnetic moments per cluster were found to be increased with size, whereas those
      per Au-S bond were nearly constant. This finding suggests that a localized hole
      created by Au-S bonding at the gold/glutathione interface, rather than the
      quantum size effect, is responsible for the spin polarization of gold clusters.

PMID- 16967931
TI  - Ionic conductivity in crystalline PEO6:Li(AsF6)1-x(SbF6)x.
AB  - The ionic conductivity of PEO6:LiXF6 (X = As, Sb) complexes may be raised by over
      an order of magnitude by forming solid solutions of PEO6:Li(AsF6)1-x(SbF6)x.

PMID- 16967932
TI  - Solvatochromism of the green fluorescence protein chromophore and its
      derivatives.
AB  - The solvatochromic behavior of the green fluorescence protein (GFP) chromophore
      (p-hydroxybenzylideneimidazolone, p-HBDI) and its derivatives (p
      methoxybenzylideneimidazolone, p-MeOBDI, and N-methyl-p
      hydroxybenzylideneimidazolonium iodide, p-HBDIMe+) was studied using UV-vis
      absorption spectroscopy in a wide array of solvents. The relative contribution of
      specific (polarity) vs nonspecific (hydrogen-bonding) solvation to the absorbance
      spectra was studied. On the basis of these data, we discuss the nature of the
      absorption peak of the protonated and deprotonated forms of the wild-type GFP.

PMID- 16967933
TI  - Improved photostable FRET-competent biarsenical-tetracysteine probes based on
      fluorinated fluoresceins.
AB  - We have developed fluoro-substituted versions of the biarsenical-tetracysteine
      label FlAsH, exhibiting significant improvements in important properties over the
      original fluorescein derivative. In complexes with tetracysteine targets, F2FlAsH
      exhibits 50 times improved photostability, lower pH sensitivity, higher
      absorbance and quantum yield than FlAsH, and F4FlAsH adds a new color to the
      palette of biarsenical dyes. The two probes also provide a new FRET pair with a
      larger Ro value (54 A) than any previously obtained with biarsenical dyes.

PMID- 16967934
TI  - Selective ion-binding by protein probed with the 3D-RISM theory.
AB  - Cations (Ca2+, Na+, K+) selectively bound by human lysozyme and its mutants are
      probed by the 3D-RISM theory, a statistical mechanics theory of liquids.

PMID- 16967935
TI  - Conductive wiring of immobilized photosynthetic reaction center to electrode by
      cytochrome C.
AB  - The photosynthetic reaction center (RC) found in photosynthetic bacteria is one
      of the most advanced photoelectronic devices developed by nature. However, after
      immobilization on the electrode surface, the efficiency of electron transfer (ET)
      between the RC and the electrode is relatively low. This inefficiency has limited
      the possibility of using the RC for technological applications. Here we show that
      photoinduced electron transfer between the immobilized RC and a gold electrode
      can be increased by several tens-fold by incorporation of cytochrome c into the
      RC-self-assembled monolayer (SAM)-electrode complex. The effect does not depend
      on the initial redox state of the cytochrome and seems to be the result of the
      formation of a complex between the RC and the cytochrome c serving as an ET wire.
      This observation opens the possibility for electrochemical analysis of the
      special pair in the RC protein that is deeply buried inside the protein globe and
      is barely electrically addressable from the electrode surface.

PMID- 16967936
TI  - Multiple deprotonations and deaminations of phenethylamines to synthesize
      pyrroles.
AB  - A unique method was discovered to construct polysubstituted pyrroles via an
      unprecedented multiple deprotonations/deaminations process from commercially
      available phenethylamines. During this transformation, twelve bonds were broken
      and five new bonds were constructed.

PMID- 16967937
TI  - Efficient catalysis of ammonia borane dehydrogenation.
AB  - In the presence of an iridium pincer complex, dehydrogenation of ammonia borane
      (H3NBH3) occurs rapidly at room temperature in tetrahydrofuran to generate 1.0
      equivalent of H2 and [NH2BH2]5. A metal borohydride complex has been isolated as
      a dormant form of the catalyst which can be reactivated by reaction with H2.

PMID- 16967939
TI  - Dynamic electronic structure of a Au/TiO2 catalyst under reaction conditions.
AB  - The electronic structure of a highly active Au/TiO2 powder catalyst was probed in
      situ by synchrotron X-ray photoelectron spectroscopy (XPS) in the 10-1 mbar
      range. The electronic structure of the Au component was found to respond
      sensitively to changes in temperature and indicated the absence of bulklike
      metallic Au under the conditions of highest catalytic activity. Concurrent
      modification of interfacial sites adjacent to Au on the TiO2 support was not
      evident from the Ti photoemission, but may have been below the detection limit of
      XPS.

PMID- 16967938
TI  - Gold-catalyzed 1,2-migration of silicon, tin, and germanium en route to C-2
      substituted fused pyrrole-containing heterocycles.
AB  - An efficient method for the synthesis of fused pyrroloheterocycles from diverse
      propargyl-substituted heterocycles in the presence of Au-catalyst has been
      developed. The cascade transformation proceeds via alkyne-vinylidene
      isomerization with concomitant 1,2-shift of hydrogen, silyl, and stannyl groups.
      Remarkably, it was also shown that previously unknown 1,2-migration of a germyl
      group upon alkyne-vinylidene rearrangement occurs under these reaction
      conditions. This method allows for mild and efficient synthesis of diverse C-2
      substituted N-containing heterocycles.

PMID- 16967940
TI  - A Re(CO)5 fragment bonded to a polyhedral oligomeric hydroxysilsesquioxane as a
      model which gives further evidence to the existence of an unexpected Re(CO)5
      surface species.
AB  - Reaction of Re(CO)5O3SCF3 with (c-C6H11)7Si8O12O-Li+ at 273 K under a CO
      atmosphere affords the [Re(CO)5OR] (R = (c-C6H11)7Si8O12) derivative (1). 1 is
      the first example of a rhenium pentacarbonyl bearing an OR ligand (R = alkyl,
      aryl, or silyl) stable enough to be characterized, and it represents also the
      first molecular model of the surface [Re(CO)5OSi] species formed by reductive
      carbonylation of silica-supported [Re(CO)3OH]4. At room temperature, 1 loses one
      carbonyl ligand and dimerizes to afford {Re(CO)4[(mu-O)O12Si8(c-C6H11)7]}2 (2),
      which has been characterized by X-ray diffraction and is the first reported
      example of a rhenium tetracarbonyl mu-oxo-bridged dimer of the type [Re(CO)4(mu
      OR)]2.

PMID- 16967941
TI  - On the versatile and unusual coordination behavior of ambiphilic ligands o
      R2P(Ph)BR'2.
AB  - Monophosphine-boranes were shown to behave as bidentate ambiphilic ligands, whose
      structural versatility has been illustrated by the preparation of PdII and AuI
      complexes featuring unusual P --> M-Cl --> B and P --> M --> B interactions,
      respectively.

PMID- 16967942
TI  - Total degradation of fenitrothion and other organophosphorus pesticides by
      catalytic oxidation employing Fe-TAML peroxide activators.
AB  - A Fe-TAML/H2O2 catalytic oxidation process achieves facile in-solution total
      degradation of fenitrothion and two other organophosphorus (OP) pesticides.
      Degradation products have been identified and quantified providing evidence for
      oxidative hydrolysis, oxidative desulfuration, perhydrolysis, and deep oxidation.
      Degradation pathways can be selected by pH control to completely obviate all
      toxic residuals. Aquatic toxicity assays support the environmental compatibility
      of the degradation process.

PMID- 16967943
TI  - cis-trans formic acid dimer: experimental observation and improved stability
      against proton tunneling.
AB  - We prepared the first cis-trans dimer of formic acid and measured its vibrational
      spectrum in a low-temperature Ar matrix. This preparation was done by selective
      vibrational excitation of the trans-trans noncyclic dimer. It was found that the
      stability of the cis-trans dimer against proton tunneling is strongly improved
      compared to the monomer, especially at elevated temperatures (>30 K). This
      surprising phenomenon was explained by differences in dynamical, energetic, and
      vibrational properties of the dimer and monomer. The obtained results show that
      the proton tunneling reactions can be strongly modified in the hydrogen-bonded
      solid network compared to the monomeric species.

PMID- 16967944
TI  - Synthesis of indenyl ethers by gold(I)-catalyzed intramolecular carboalkoxylation
      of alkynes.
AB  - The gold(I)-catalyzed carboalkoxylation of alkynes to form indanone derivatives
      from readily available ortho-acetylenic benzylic ethers is described.
      Importantly, the gold(I)-catalyzed rearrangement of enantioenriched benzylic
      ethers proceeds with chirality transfer, thus providing a practical method for
      the enantioselective synthesis of indenyl ethers.

PMID- 16967945
TI  - In situ fabrication of a water-soluble, self-doped polyaniline nanocomposite: the
      unique role of DNA functionalized single-walled carbon nanotubes.
AB  - Dispersion of carbon nanotubes into solvents affects their surface chemistries,
      electronic structures, and subsequent functionalization. In this Communication, a
      water-soluble self-doped polyaniline nanocomposite was fabricated by in situ
      polymerization of the 3-aminophenylboronic acid monomers in the presence of
      single-stranded DNA dispersed- and functionalized-single-walled carbon nanotubes.
      For the first time, we found that the carbon nanotubes became novel active
      stabilizers owing to the DNA functionalization. The nanotubes reduced the
      polyaniline backbone from the unstable, degradable, fully oxidized pernigraniline
      state to the stable, conducting emeraldine state because of their reductive
      ability, which could improve the chemical stability of the self-doped
      polyaniline. Electrical measurements demonstrate that the conductivity of the
      nanocomposite was much higher than that of the pure self-doped polyaniline in
      both acidic and neutral solutions.

PMID- 16967946
TI  - Mixed-valence two-legged MX-ladder complex with a pair of out-of-phase charge
      density waves.
AB  - A novel two-legged MX-ladder complex {[(dien)PtIVBr2-bpy
      PtII(dien)]Br4.2H2O}infinity was synthesized and analyzed by single-crystal X-ray
      diffraction method and Raman and diffuse reflectance spectra. The electronic
      structure on two-legged MX-ladder is a pair of out-of-phase charge-density-waves
      state within each ladder, and these pairs of CDWs are also ordered from ladder to
      ladder. The intervalence charge-transfer (PtII to PtIV) excitation energy is
      significantly larger than that in the MX-chain system because of the intersite
      Coulomb repulsion along the rung.

PMID- 16967947
TI  - Unusual non-bulk properties in nanoscale materials: thermal metal-metal bond
      contraction of gamma-alumina-supported Pt catalysts.
AB  - Variable-temperature X-ray absorption spectroscopy measurements of sub-nanometer
      Pt nanoparticles on a high-surface-area gamma-alumina support reveal that the Pt
      Pt bonds exhibit contraction upon heating [i.e., negative thermal expansion
      (NTE)]. Bare clusters under a He environment show an average linear expansion
      coefficient of -2.5 x 10-5 K-1 over the temperature range studied. Adsorption of
      hydrogen results in an overall bond relaxation and less dramatic Pt-Pt thermal
      bond-length contraction. From the temperature effect on bond length, disorder
      parameters, and the X-ray absorption near edge structure (XANES) spectra,
      temperature-dependent charge transfer between the support and the Pt clusters was
      concluded to be responsible for the observed behavior.

PMID- 16967948
TI  - Electron paramagnetic resonance studies of an integral membrane peptide inserted
      into aligned phospholipid bilayer nanotube arrays.
AB  - This communication reports for the first time the determination of the helical
      tilt of an integral membrane peptide inserted into aligned phospholipids bilayer
      nanotube arrays using spin label EPR spectroscopy. Also, we demonstrate herein
      how the helical tilt of the peptide can be easily calculated using the hyperfine
      splitting values gleaned from a perpendicularly aligned bilayer in phospholipid
      bilayer nanotube arrays. EPR spectral simulations were used to verify the method.

PMID- 16967949
TI  - Copolymerization of silyl vinyl ethers with olefins by (alpha-diimine)PdR+.
AB  - This paper reports that (alpha-diimine)PdMe+ catalyzes the copolymerization of
      olefins and silyl vinyl ethers. The reactions of (alpha-diimine)PdMe+ (alpha
      diimine = (2,6-iPr2-C6H3)N=CMe-CMe=N(2,6-iPr2-C6H3)) with excess vinyl ethers
      CH2=CHOR (1a-d: R = tBu (a), SiMe3 (b), SiPh3 (c), Ph (d)) in CH2Cl2 at 20
      degrees C afford polymers for 1a (rapidly) and 1b (slowly) but not for 1c or 1d.
      The structures of poly(1a,b) indicate a cationic polymerization mechanism. The
      reaction of (alpha-diimine)PdMe+ with 1-2 equiv of 1a-d proceeds by sequential
      C=C pi-complexation to form (alpha-diimine)PdMe(CH2=CHOR)+ (2a-d), 1,2 insertion
      to form (alpha-diimine)Pd(CH2CHMeOR)+ (3a-d), reversible isomerization to (alpha
      diimine)Pd(CMe2OR)+ (4a-d), beta-OR elimination to generate (alpha
      diimine)Pd(OR)(CH2=CHMe)+ (not observed), and allylic C-H activation to yield
      (alpha-diimine)Pd(eta3-C3H5)+ (5) and ROH. The reaction of (alpha-diimine)PdMe+
      with 1-hexene/1b and 1-hexene/1c mixtures in CH2Cl2 at 20 degrees C affords
      copolymers containing up to 20 mol % silyl vinyl ether. The copolymers were
      purified to be free of any -[CH2CHOSiR3]n- homopolymer. The copolymer structures
      are similar to that of homopoly(1-hexene) generated under the same conditions.
      The major comonomer units are CH3CH(OSiR3)CH2-, CH2(OSiR3)CH2- and 
      CH2CH(OSiR3)CH2-. The 1-hexene/CH2=CHOSiR3 copolymers can be desilylated to give
      1-hexene/CH2=CHOH copolymers. The results of control experiments argue against
      cationic and radical mechanisms for the copolymerization, and an insertion/chain
      walking mechanism is proposed.

PMID- 16967950
TI  - Generalized route to metal nanoparticles with liquid behavior.
AB  - We report the generalized synthesis of metal nanoparticles with liquid-like
      behavior. We introduce a thiol-containing ionic liquid, N,N-dioctyl-N-(3
      mercaptopropyl)-N-methylammonium bromide, which serves as a ligand for platinum,
      gold, palladium, and rhodium nanoparticles. A rapid reduction using THF-soluble
      metal salts in the presence of the thiol generates nanoparticles with tunable
      sizes and size distributions. The as-synthesized nanoparticles are a solid and
      decompose before melting. Upon exchange of the halide anion for an amphiphilic
      sulfonate anion, however, the nanoparticles exhibit liquid-like properties at
      room temperature. The liquids have high metal loadings; for example, the 2.7 nm
      platinum nanoparticle liquid is 36% platinum by mass.

PMID- 16967951
TI  - Transfer of surface polymerase reaction products to a secondary platform with
      conservation of spatial registration.
AB  - Here, we describe a method for directly transferring very small amounts of
      reaction products from one surface to another. The approach is illustrated using
      a T4 DNA polymerase reaction to extend primers hybridized to a surface-confined
      DNA template. Following the extension reaction, the resulting oligonucleotide is
      transferred to a product surface. The important results are that (1) the spatial
      registration of the product is preserved after transfer; (2) the same reactant
      surface can be used to generate and transfer multiple iterations of products; and
      (3) the reaction products are biologically active after transfer.

PMID- 16967952
TI  - A chemical reporter strategy to probe glycoprotein fucosylation.
AB  - Fucosylated glycoproteins are involved in many cell-cell recognition events and
      are markers of embryonic and malignant tissue. Here we report a method for rapid
      profiling of fucosylated glycoproteins from human cells using 6-azido fucose as a
      metabolic label.

PMID- 16967953
TI  - Force-controlled inorganic crystallization lithography.
AB  - Lithography plays a key role in integrated circuits, optics, information
      technology, biomedical applications, catalysis, and separation technologies.
      However, inorganic lithography techniques remain of limited utility for
      applications outside of the typical foci of integrated circuit manufacturing. In
      this communication, we have developed a novel stamping method that applies
      pressure on the upper surface of the stamp to regulate the dewetting process of
      the inorganic buffer and the evaporation rate of the solvent in this buffer
      between the substrate and the surface of the stamp. We focused on generating
      inorganic microstructures with specific locations and also on enabling the
      ability to pattern gradients during the crystallization of the inorganic salts.
      This approach utilized a combination of lithography with bottom-up growth and
      assembly of inorganic crystals. This work has potential applications in a variety
      of fields, including studying inorganic material patterning and small-scale
      fabrication technology.

PMID- 16967954
TI  - Direct electrochemistry of endonuclease III in the presence and absence of DNA.
AB  - The electrochemistry of the base excision repair enzyme Endonuclease III (Endo
      III) in the presence and absence of DNA has been examined on highly oriented
      pyrolytic graphite (HOPG). At the surface modified with pyrenated DNA, a
      reversible signal is observed at 20 mV versus NHE for the [4Fe-4S]3+/2+ couple of
      Endo III, similar to Au. Without DNA modification, oxidative and reductive
      signals for the [4Fe-4S] cluster of Endo III are found on bare HOPG, allowing a
      direct comparison between DNA-bound and free redox potentials. These data
      indicate a shift of approximately -200 mV in the 3+/2+ couple upon binding of
      Endo III to DNA. This potential shift reflects a difference in affinity for DNA
      of more than 3 orders of magnitude between the oxidized 3+ and reduced 2+ protein
      and provides quantitative support for our model utilizing DNA-mediated charge
      transport to redistribute base excision repair enzymes in the vicinity of damaged
      DNA.

PMID- 16967955
TI  - A versatile new monomer family: functionalized 4-vinyl-1,2,3-triazoles via click
      chemistry.
AB  - Using facile, highly modular synthetic approaches, a new monomer family based on
      a 1,2,3-triazole-4-vinyl building block has been prepared, and various functional
      derivatives have been obtained. Subsequent homo- and copolymerization of these
      novel functionalized monomers gives polymeric materials with unique physical
      properties, combining many attractive features of more traditional monomers, such
      as styrene, vinylpyridine, and meth/acrylates.

PMID- 16967956
TI  - Constrained-geometry aluminum complexes with eta5;eta1-coordination: syntheses,
      structures, and theoretical studies of dicarbollylamino aluminum(III) complexes.
AB  - A series of constrained geometry complexes of formula [(eta5-RC2B9H10)CH2(eta1
      NMe2)]Al(Me) (R = H, 2a; Me, 2b) was prepared in high yields from the reaction of
      dicarbollylamine with trimethylaluminum. These complexes showed a unique
      constrained geometry structure with a central aluminum atom having eta5;eta1
      coordination. DFT calculations further elaborate the electronic effect of an
      amine sidearm on the bonding capability of dicarbollyl ligand with an aluminum
      atom. It has been noted that dicarbollylamines are effective ancillary ligands
      for the production of novel constrained geometry complexes of aluminum.

PMID- 16967957
TI  - Reversible alkene extrusion from platinaoxetanes.
AB  - Reversible alkene extrusion from platinaoxetanes has been observed. Catalytic
      amounts of electrophilic Pt complexes, HOTf, Ag+, or BF3 (best) result in
      dramatic rate enhancements.

PMID- 16967958
TI  - Unusual hydrogen bonding in water-filled carbon nanotubes.
AB  - We present the first experimental vibrational spectroscopy study providing direct
      evidence of a water phase inside single-walled carbon nanotubes that exhibits an
      unusual form of hydrogen-bonding due to confinement. Water adopts a stacked-ring
      structure inside nanotubes, forming intra- and inter-ring hydrogen bonds. The
      intra-ring hydrogen bonds are bulk-like while the inter-ring hydrogen bonds are
      relatively weak, having a distorted geometry that gives rise to a distinct OH
      stretching mode. The experimentally observed infrared mode at 3507 cm(-1) is
      assigned to vibrations of the inter-ring OH-groups based on detailed atomic-level
      modeling. The direct observation of unusual hydrogen bonding in nanotubes has
      potential implications for water in other highly confined systems, such as
      biological channels and nanoporous media.

PMID- 16967959
TI  - Atomically detailed simulations of concentrated protein solutions: the effects of
      salt, pH, point mutations, and protein concentration in simulations of 1000
      molecule systems.
AB  - An ability to accurately simulate the dynamic behavior of concentrated
      macromolecular solutions would be of considerable utility in studies of a wide
      range of biological systems. With this goal in mind, a Brownian dynamics (BD)
      simulation method is reported here that allows systems to be modeled that
      comprise in excess of 1000 protein molecules, all of which are treated in atomic
      detail. Intermolecular forces are described in the method using an energy
      function that incorporates electrostatic and hydrophobic interactions and that is
      calibrated to reproduce experimental thermodynamic information with a single
      adjustable parameter. Using the method, BD simulations have been performed over a
      wide range of pH and ionic strengths for three proteins: hen egg white lysozyme
      (HEWL), chymotrypsinogen, and T4 lysozyme. The simulations reproduce experimental
      trends in second virial coefficients (B(22)) and translational diffusion
      coefficients, correctly capture changes in B(22) values due to single amino acid
      substitutions, and reveal a new explanation for the difficulties reported
      previously in the literature in reproducing B(22) values for protein solutions of
      very low ionic strength. In addition, a strong correlation is found between a
      residue's probability of being involved in a protein-protein contact in the
      simulations and its probability of being involved in an experimental crystal
      contact. Finally, exploratory simulations of HEWL indicate that the simulation
      model also gives a promising description of behavior at very high protein
      concentrations (approximately 250 g/L), suggesting that it may provide a suitable
      computational framework for modeling the complex behavior exhibited by
      macromolecules in cellular conditions.

PMID- 16967960
TI  - Microsolvation of formamide: a rotational study.
AB  - Microsolvated formamide clusters have been generated in a supersonic jet
      expansion and characterized using Fourier transform microwave spectroscopy. Three
      conformers of the monohydrated cluster and one of the dihydrated complex have
      been observed. Seven monosubstituted isotopic species have been measured for the
      most stable conformer of formamide...H(2)O, which adopts a closed planar ring
      structure stabilized by two intermolecular hydrogen bonds (N-H...O(H)-H...O=C).
      The two higher energy forms of formamide...H(2)O have been observed for the first
      time. The second most stable conformer is stabilized by a O-H...O=C and a weak C
      H...O hydrogen bond, while, in the less stable form, water accepts a hydrogen
      bond from the anti hydrogen of the amino group. For formamide...(H(2)O)(2), the
      parent and nine monosubstituted isotopic species have been observed. In this
      cluster the two water molecules close a cycle with the amide group through three
      intermolecular hydrogen bonds (N-H...O(H)-H...O(H)-H...O=C), the nonbonded
      hydrogen atoms of water adopting an up-down configuration. Substitution (r(s))
      and effective (r(0)) structures have been determined for formamide, the most
      stable form of formamide...H(2)O and formamide...(H(2)O)(2). The results on
      monohydrated formamide clusters can help to explain the observed preferences of
      bound water in proteins. Clear evidence of sigma-bond cooperativity effects
      emerges when comparing the structures of the mono- and dihydrated formamide
      clusters. No detectable structural changes due to pi-bond cooperativity are
      observed on formamide upon hydration.

PMID- 16967961
TI  - Solvent-induced effects: self-association of positively charged pi systems.
AB  - Antimalarial cationic drugs, such as chloroquine (CQ) and ferroquine (FQ), form
      stable dimer structures not only in the solid state but also in solution. The
      short distances (3.3-3.5 A) observed between the positively charged quinolinium
      rings suggest that this self-association process is driven by pi/pi stacking
      interactions. Nevertheless, the strength of these dispersive forces is likely not
      sufficient to overcome the strong repulsive +/+ electrostatic effects. The
      question of the exact role of the environment, particularly the solvent, is
      clearly raised here. Characterization of these unconventional stabilizing
      nonbonding interactions which we have named +-pi/+-pi is therefore of great
      importance. In the present work, we describe theoretical calculations and NMR
      experiments undertaken to probe the nature and the strength of +-pi/+-pi
      interactions occurring upon self-association of FQ and CQ molecules in water.

PMID- 16967962
TI  - Influence of the membrane potential on the protonation of bacteriorhodopsin:
      insights from electrostatic calculations into the regulation of proton pumping.
AB  - Proton binding and release are elementary steps for the transfer of protons
      within proteins, which is a process that is crucial in biochemical catalysis and
      biological energy transduction. Local electric fields in proteins affect the
      proton binding energy compared to aqueous solution. In membrane proteins, also
      the membrane potential affects the local electrostatics and can thus be crucial
      for protein function. In this paper, we introduce a procedure to calculate the
      protonation probability of titratable sites of a membrane protein in the presence
      of a membrane potential. In the framework of continuum electrostatics, we use a
      modified Poisson-Boltzmann equation to include the influence of the membrane
      potential. Our method considers that in a transmembrane protein each titratable
      site is accessible for protons from only one side of the membrane depending on
      the hydrogen bond pattern of the protein. We show that the protonation of sites
      receiving their protons from different sides of the membrane is differently
      influenced by the membrane potential. In addition, the effect of the membrane
      potential is combined with the effect of the pH gradient resulting from proton
      pumping. Our method is applied to bacteriorhodopsin, a light-activated proton
      pump. We find that the proton pumping of this protein might be regulated by
      Asp115, a conserved residue for which no function has been identified yet.
      According to our calculations, the interaction of Asp115 with Asp85 leads to the
      protonation of the latter if the pH gradient or the membrane potential becomes
      too large. Since Asp85 is the primary proton acceptor in the photocycle,
      bacteriorhodopsin molecules in which Asp85 is protonated cannot pump protons.
      Furthermore, we estimate how the membrane potential affects the energetics of the
      individual proton-transfer reactions of the photocycle. Most reactions, except
      the initial proton transfer from the Schiff base to Asp85, are influenced. Our
      calculations give new insights into the mechanism with which bacteriorhodopsin
      senses the membrane potential and the pH gradient and how the proton pumping is
      regulated by these parameters.

PMID- 16967963
TI  - Automated search for new thermoelectric materials: the case of LiZnSb.
AB  - An automated band structure calculation based on the inorganic crystal structure
      database and the augmented plane wave method for electronic structure
      calculations is presented. Using a rigid band approach and semiclassic Boltzmann
      theory the band structures are analyzed and a large number of compounds are
      screened for potential interesting thermoelectric properties. We thereby propose
      LiZnSb as a potential new thermoelectric material. The k-space structure of the
      lowest conduction band of LiZnSb is analyzed in detail, and excellent
      thermoelectric properties are expected for this material. Furthermore the lattice
      dynamics are calculated, and anisotropic lattice thermal conduction is predicted.

PMID- 16967964
TI  - X-ray diffraction area mapping of preferred orientation and phase change in TiO2
      thin films deposited by chemical vapor deposition.
AB  - This paper reports on an investigation into the formation of TiO(2) thin films,
      whereby X-ray diffraction is used to map systematic changes in preferred
      orientation and phase observed throughout the films. The key to this strategy is
      the recording of X-ray diffraction patterns of specific and isolated areas of a
      substrate, ensuring this specificity by the use of a small X-ray sample
      illumination area (approximately 3-5 mm(2)). A map of the variation in film
      composition can then be built up by recording such diffraction patterns at
      regular intervals over the whole substrate. Two titania films will be presented,
      grown using atmospheric pressure chemical vapor deposition, at 450 and 600
      degrees C, from TiCl(4) and ethyl-acetate precursors. The film grown at 450
      degrees C showed a systematic change in preferred orientation, while the film
      grown at 600 degrees C was composed of a mixture of the rutile and anatase phases
      of TiO(2) with the ratio of these phases altering with position on the substrate.
      The results of physical property measurements and electron microscopy carried out
      on the films are also reported, conducted at locations identified by the X-ray
      diffraction mapping procedure as having different compositions, and hence
      different physical responses. We found that the photocatalytic activity and
      hydrophobicity were dependent on the rutile:anatase ratio at any given location
      on the film.

PMID- 16967965
TI  - Antimicrobial peptides in action.
AB  - Molecular dynamics simulations of the magainin MG-H2 peptide interacting with a
      model phospholipid membrane have been used to investigate the mechanism by which
      antimicrobial peptides act. Multiple copies of the peptide were randomly placed
      in solution close to the membrane. The peptide readily bound to the membrane, and
      above a certain concentration, the peptide was observed to cooperatively induce
      the formation of a nanometer-sized, toroidally shaped pore in the bilayer. In
      sharp contrast with the commonly accepted model of a toroidal pore, only one
      peptide was typically found near the center of the pore. The remaining peptides
      lay close to the edge of the pore, maintaining a predominantly parallel
      orientation with respect to the membrane.

PMID- 16967966
TI  - Sequence-specific alkylation of double-strand human telomere repeat sequence by
      pyrrole-imidazole polyamides with indole linkers.
AB  - We designed and synthesized pyrrole (Py)-imidazole (Im) hairpin polyamide 1
      (chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI) conjugates 1 and
      2, which target both strands of the double-stranded region of the human telomere
      repeat sequences, 5'-d(TTAGGG)(n)-3'/5'-d(CCCTAA)(n)-3'. High-resolution
      denaturing polyacrylamide gel electrophoresis demonstrated that conjugates 1 and
      2 alkylated DNA at the 3' A of 5'-ACCCTA-3' and 5'-AGGGTTA-3', respectively.
      Cytotoxicities of conjugates 1 and 2 were evaluated using 39 human cancer cell
      lines; averages of log IC(50) values for conjugates 1 and 2 were -6.96 (110 nM)
      and -7.24 (57.5 nM), respectively. Conjugates 1 and 2 have potential as antitumor
      drugs capable of targeting telomere repeat sequence.

PMID- 16967967
TI  - Circumambulatory rearrangement with characteristics of a 2:1 covalent molecular
      bevel gear.
AB  - anti-W(CO)(5)-complexed 9-methyl-9-phosphabicyclo[6.1.0]nonatriene represents a
      covalently interlocked molecular bevel gear. Correlated movement of the
      phosphorus atom and the eight-membered ring by way of a "walk" rearrangement
      makes gear slippage impossible. The gearing motion is transferred to the four
      toothed W(CO)(5) propeller connected to the rotating phosphorus atom, enabling a
      gearing ratio of 2:1 according to B3LYP and Car-Parrinello Molecular Dynamics
      calculations. Methyl substitution of the eight-membered ring tempers the gearing
      process, with the PMeW(CO)(5) entity passing the substituted carbon atom only at
      temperatures above 50 degrees C.

PMID- 16967969
TI  - Serendipity and four polymorphic structures of benzidine, C12H12N2.
AB  - The search for a co-crystal of benzidine as a bifunctional hydrogen-bond donor
      with potential hydrogen-bond acceptors has instead revealed four polymorphs of
      the source material benzidine for which, somewhat surprisingly, no structure has
      been reported as of the November 2005 update of the CSD. All four structures are
      characterized by a rather unusual number of molecules in the asymmetric unit (Z'
      = 1.5, 3, and 4.5), which are found in only 0.25%, 0.4%, and 0.002% of structures
      in the CSD. Forms I and IV (Z' = 4.5) exhibit very similar crystal habits and are
      not distinguishable visually. In all forms except Form II (Z' = 3), one of the
      molecules lies on a crystallographic inversion center, requiring the molecule to
      be planar; other molecules are nonplanar. Spectroscopic and thermodynamic
      characterizations of the system, including at least two possible additional forms
      of benzidine obtained by HT polymorph screening are reported.

PMID- 16967968
TI  - Synthesis and evaluation of bioorthogonal pantetheine analogues for in vivo
      protein modification.
AB  - In vivo carrier protein tagging has recently become an attractive target for the
      site-specific modification of fusion systems and new approaches to natural
      product proteomics. A detailed study of pantetheine analogues was performed in
      order to identify suitable partners for covalent protein labeling inside living
      cells. A rapid synthesis of pantothenamide analogues was developed and used to
      produce a panel which was evaluated for in vitro and in vivo protein labeling.
      Kinetic comparisons allowed the construction of a structure-activity relationship
      to pinpoint the linker, dye, and bioorthogonal reporter of choice for carrier
      protein labeling. Finally bioorthogonal pantetheine analogues were shown to
      target carrier proteins with high specificity in vivo and undergo chemoselective
      ligation to reporters in crude cell lysate. The methods demonstrated here allow
      carrier proteins to be visualized and isolated for the first time without the
      need for antibody techniques and set the stage for the future use of carrier
      protein fusions in chemical biology.

PMID- 16967970
TI  - Pentacyanoiron(II) as an electron donor group for nonlinear optics: medium
      responsive properties and comparisons with related pentaammineruthenium(II)
      complexes.
AB  - In this article, we describe a series of complex salts in which electron-rich
      {Fe(II)(CN)(5)}(3)(-) centers are coordinated to pyridyl ligands with electron
      accepting N-methyl/aryl-pyridinium substituents. These compounds have been
      characterized by using various techniques including electronic absorption
      spectroscopy and cyclic voltammetry. Molecular quadratic nonlinear optical (NLO)
      responses have been determined by using hyper-Rayleigh scattering (HRS) at 1064
      nm, and also via Stark (electroabsorption) spectroscopic studies on the intense,
      visible d --> pi* metal-to-ligand charge-transfer (MLCT) bands. The relatively
      large static first hyperpolarizabilities, beta(0), increase markedly on moving
      from aqueous to methanol solutions, accompanied by large red-shifts in the MLCT
      transitions. Acidification of aqueous solutions allows reversible switching of
      the linear and NLO properties, as shown via both HRS and Stark experiments. Time
      dependent density functional theory and finite field calculations using a
      polarizable continuum model yield relatively good agreement with the experimental
      results and confirm the large decrease in beta(0) on protonation. The Stark
      derived beta(0) values are generally larger for related {Ru(II)(NH(3))(5)}(2+)
      complexes than for their {Fe(II)(CN)(5)}(3)(-) analogues, consistent with the HRS
      data in water. However, the HRS data in methanol show that the stronger
      solvatochromism of the Fe(II) complexes causes their NLO responses to surpass
      those of their Ru(II) counterparts upon changing the solvent medium.

PMID- 16967971
TI  - Microfluidic production of biopolymer microcapsules with controlled morphology.
AB  - We report a microfluidic approach to generating capsules of biopolymer hydrogels.
      Droplets of an aqueous solution of a biopolymer were emulsified in an organic
      phase comprising a cross-linking agent. Polymer gelation was achieved in situ (on
      a microfluidic chip) by diffusion-controlled ionic cross-linking of the
      biopolymer, following the transfer of the cross-linking agent from the continuous
      phase to the droplets. Gelation was quenched by collecting particles in a large
      pool of cross-linking agent-free liquid. The structure of microgels (from
      capsules to gradient microgels to particles with a uniform structure) was
      controlled by varying the time of residence of droplets on the microfluidic chip
      and the concentration of the cross-linking agent in the continuous phase. We
      demonstrated the encapsulation of a controlled number of polystyrene beads in the
      microgel capsules. The described approach was applied to the preparation of
      capsules of several polysaccharides such as alginate, kappa-carrageenan, and
      carboxymethylcellulose.

PMID- 16967972
TI  - Catalyzed relaxation of a metastable DNA fuel.
AB  - Practically all of life's molecular processes, from chemical synthesis to
      replication, involve enzymes that carry out their functions through the catalytic
      transformation of metastable fuels into waste products. Catalytic control of
      reaction rates will prove to be as useful and ubiquitous in nucleic-acid-based
      engineering as it is in biology. Here we report a metastable DNA "fuel" and a
      corresponding DNA "catalyst" that improve upon the original hybridization-based
      catalyst system (Turberfield et al. Phys. Rev. Lett. 90, 118102-1-118102-4) by
      more than 2 orders of magnitude. This is achieved by identifying and purifying a
      fuel with a kinetically trapped metastable configuration consisting of a "kissing
      loop" stabilized by flanking helical domains; the catalyst strand acts by opening
      a helical domain and allowing the complex to relax to its ground state by a
      multistep pathway. The improved fuel/catalyst system shows a roughly 5000-fold
      acceleration of the uncatalyzed reaction, with each catalyst molecule capable of
      turning over in excess of 40 substrates. With k(cat)/K(M) approximately
      10(7)/M/min, comparable to many protein enzymes and ribozymes, this fuel system
      becomes a viable component enabling future DNA-based synthetic molecular machines
      and logic circuits. As an example, we designed and characterized a signal
      amplifier based on the fuel-catalyst system. The amplifier uses a single strand
      of DNA as input and releases a second strand with unrelated sequence as output. A
      single input strand can catalytically trigger the release of more than 10 output
      strands.

PMID- 16967973
TI  - Stereochemical and regiochemical trends in the selective detection of
      saccharides.
AB  - Several discreet sugar-boronate complexes exist in solution. This is due to the
      complex equilibria between isomeric species of even the simplest monosaccharides.
      In the current investigation, we determine the regio- and stereochemical features
      of the various equilibrating sugar isomers that induce signal transduction in
      boronic acid chemosensors such as 1 as well as 2 and 3. We present a unique
      example of a chemosensor (1) that is selective for ribose, adenosine,
      nucleotides, nucleosides, and congeners. As a result of this study, we are able
      to predict and achieve selective fluorescence and colorimetric responses to
      specific disaccharides as a consequence of their terminal sugar residue linkage
      patterns and configurations. We also find that the combined use of chemosensors
      exhibiting complementary reactivities may be used cooperatively to obtain
      enhanced selectivity for ribose and rare saccharides.

PMID- 16967974
TI  - Determining the intracellular transport mechanism of a cleft-[2]rotaxane.
AB  - Rotaxanes are a class of interlocked compounds that have been extensively
      investigated for their potential utility as switches or sensors. We recently
      demonstrated that rotaxanes have further application as agents that transport
      material into cells. This novel finding prompted our investigation into the
      mechanism by which rotaxanes are involved in transmembrane transport. Two
      dimensional NMR analysis showed that a cleft-containing rotaxane exists in two
      dominant conformations ("closed" and "open"). To determine the importance of
      conformational flexibility on the ability of the rotaxanes to bind guests and
      transport material into cells, the rotaxane was chemically modified to lock it in
      the closed conformation. Charged guests interact less favorably with the locked
      rotaxane, as compared to the unmodified rotaxane, both in an aqueous solution and
      in DMSO. In a chloroform solution, both rotaxanes bind the guests with similar
      affinities. The locked rotaxane exhibited a reduced capacity to transport a
      fluoresceinated peptide into cells, whereas the unmodified rotaxane efficiently
      delivers the peptide. Flow cytometry experiments demonstrated that a high
      percentage of the cells contained the delivered peptide (89-98%), the level of
      delivery is concentration dependent, and the rotaxanes and peptide have low
      toxicity. Cellular uptake of the peptide was largely temperature and ATP
      independent, suggesting that the rotaxane-peptide complex passes through the
      cellular membrane without requiring active cell-mediated processes. The results
      show that the sliding motion of the wheel is necessary for the delivery of
      materials into cells and can enhance the association of guests. These studies
      demonstrate the potential for rotaxanes as a new class of mechanical devices that
      deliver a variety of therapeutic agents into targeted cell populations.

PMID- 16967975
TI  - Dispersion and separation of small-diameter single-walled carbon nanotubes.
AB  - The dispersion of small-diameter single-walled carbon nanotubes (SWNTs) produced
      by the CoMoCAT method in tetrahydrofuran (THF) with the use of amine was studied.
      The absorption, photoluminescence, and Raman spectroscopies showed that the
      dispersion and centrifugation process leads to an effective separation of
      metallic SWNTs from semiconducting SWNTs. Since this method is simple and
      convenient, it is highly applicable to an industrial utilization for widespread
      applications of SWNTs.

PMID- 16967976
TI  - Synthesis, structural studies, theoretical calculations, and linear and nonlinear
      optical properties of terpyridyl lanthanide complexes: new evidence for the
      contribution of f electrons to the NLO activity.
AB  - The synthesis and structural, photophysical, and second-order nonlinear optical
      (NLO) properties of a novel lanthanide terpyridyl-like complex family
      LLn(NO(3))(3) (Ln = La, Gd, Dy, Yb, and Y) are reported. The isostructural
      character of this series in solution and in the solid state has been established
      on the basis of X-ray diffraction analysis in the cases of yttrium and gadolinium
      complexes, theoretical optimization of geometry (DFT), and NMR spectroscopy. The
      absorption, emission, and solvatochromic properties of the free terpyridyl-like
      ligand L were thoroughly investigated, and the twist intramolecular charge
      transfer (TICT) character of the lowest energy transition was confirmed by
      theoretical calculation (TDDFT and CIS). The similar ionochromic effect of the
      different lanthanide ions was evidenced by the similar UV-visible spectra of the
      complete family of complexes. On the other hand, the quadratic
      hyperpolarizability coefficient beta, measured by the harmonic light scattering
      (HLS) technique, is clearly dependent on the nature of the metal, and a careful
      examination of the particular case of yttrium unambiguously confirms the
      contribution of metal f electrons to the NLO activity.

PMID- 16967978
TI  - Thermally stable perfluoroalkylfullerenes with the skew-pentagonal-pyramid
      pattern: C60(C2F5)4O, C60(CF3)4O, and C60(CF3)6.
AB  - Reaction of C(60) with CF(3)I at 550 degrees C, which is known to produce a
      single isomer of C(60)(CF(3))(2,4,6) and multiple isomers of C(60)(CF(3))(8,10),
      has now been found to produce an isomer of C(60)(CF(3))(6) with the C(s)
      C(60)X(6) skew-pentagonal-pyramid (SPP) addition pattern and an epoxide with the
      C(s)-C(60)X(4)O variation of the SPP addition pattern, C(s)-C(60)(CF(3))(4)O. The
      structurally similar epoxide C(s)-C(60)(C(2)F(5))(4)O is one of the products of
      the reaction of C(60) with C(2)F(5)I at 430 degrees C. The three compounds have
      been characterized by mass spectrometry, DFT quantum chemical calculations,
      Raman, visible, and (19)F NMR spectroscopy, and, in the case of the two epoxides,
      single-crystal X-ray diffraction. The compound C(s)-C(60)(CF(3))(6) is the first
      [60]fullerene derivative with adjacent R(f) groups that are sufficiently
      sterically hindered to cause the (DFT-predicted) lengthening of the cage (CF(3))C
      C(CF(3)) bond to 1.60 A as well as to give rise to a rare, non-fast-exchange
      limit (19)F NMR spectrum at 20 degrees C. The compounds C(s)-C(60)(CF(3))(4)O and
      C(s)-C(60)(C(2)F(5))(4)O are the first poly(perfluoroalkyl)fullerene derivatives
      with a non-fluorine-containing exohedral substituent and the first fullerene
      epoxides known to be stable at elevated temperatures. All three compounds
      demonstrate that the SPP addition pattern is at least kinetically stable, if not
      thermodynamically stable, at temperatures exceeding 400 degrees C. The high
      temperature synthesis of the two epoxides also indicates that perfluoroalkyl
      substituents can enhance the thermal stability of fullerene derivatives with
      other substituents.

PMID- 16967977
TI  - Structure determination of a membrane protein with two trans-membrane helices in
      aligned phospholipid bicelles by solid-state NMR spectroscopy.
AB  - The structure of the membrane protein MerFt was determined in magnetically
      aligned phospholipid bicelles by solid-state NMR spectroscopy. With two trans
      membrane helices and a 10-residue inter-helical loop, this truncated construct of
      the mercury transport membrane protein MerF has sufficient structural complexity
      to demonstrate the feasibility of determining the structures of polytopic
      membrane proteins in their native phospholipid bilayer environment under
      physiological conditions. PISEMA, SAMMY, and other double-resonance experiments
      were applied to uniformly and selectively (15)N-labeled samples to resolve and
      assign the backbone amide resonances and to measure the associated (15)N chemical
      shift and (1)H-(15)N heteronuclear dipolar coupling frequencies as orientation
      constraints for structure calculations. (1)H/(13)C/(15)N triple-resonance
      experiments were applied to selectively (13)C'- and (15)N-labeled samples to
      complete the resonance assignments, especially for residues in the nonhelical
      regions of the protein. A single resonance is observed for each labeled site in
      one- and two-dimensional spectra. Therefore, each residue has a unique
      conformation, and all protein molecules in the sample have the same three
      dimensional structure and are oriented identically in planar phospholipid
      bilayers. Combined with the absence of significant intensity near the isotropic
      resonance frequency, this demonstrates that the entire protein, including the
      loop and terminal regions, has a well-defined, stable structure in phospholipid
      bilayers.

PMID- 16967979
TI  - Calix[4]pyrrole as a chloride anion receptor: solvent and countercation effects.
AB  - The interaction of calixpyrrole with several chloride salts has been studied in
      the solid state by X-ray crystallography as well as in solution by isothermal
      titration calorimetry (ITC) and (1)H NMR spectroscopic titrations. The titration
      results in dimethylsulfoxide, acetonitrile, nitromethane, 1,2-dichloroethane, and
      dichloromethane, carried out using various chloride salts, specifically
      tetraethylammonium (TEA), tetrapropylammonium (TPA), tetrabutylammonium (TBA),
      tetraethylphosphonium (TEP), tetrabutylphosphonium (TBP), and
      tetraphenylphosphonium (TPhP), showed no dependence on method of measurement. The
      resulting affinity constants (K(a)), on the other hand, were found to be highly
      dependent on the choice of solvent with K(a)'s ranging from 10(2)-10(5) M(-1)
      being recorded in the test solvents used for this study. In dichloromethane, a
      strong dependence on the countercation was also seen, with the K(a)'s for the
      interaction with chloride ranging from 10(2)-10(4) M(-1). In the case of TPA,
      TBA, and TBP, the ITC data could not be fit to a 1:1 binding profile.

PMID- 16967980
TI  - Staurosporine and rebeccamycin aglycones are assembled by the oxidative action of
      StaP, StaC, and RebC on chromopyrrolic acid.
AB  - In the biosynthesis of the antitumor indolocarbazoles rebeccamycin and
      staurosporine by streptomycetes, assembly of the aglycones involves a complex set
      of oxidative condensations. Overall formation of aglycones K252c and
      arcyriaflavin A from their biosynthetic precursor chromopyrrolic acid involves
      four- and eight-electron oxidations, respectively. This process is catalyzed by
      the remarkable enzyme StaP, with StaC and RebC acting to direct the level of
      oxidation in the newly formed five-membered ring. An aryl-aryl coupling reaction
      is integral to this transformation as well as oxidative decarboxylation of the
      dicarboxypyrrole moiety of chromopyrrolic acid. Herein we describe the
      heterologous expression of staP, staC, and rebC in Escherichia coli and the
      activity of the corresponding enzymes in constructing the two distinct six-ring
      scaffolds. StaP is a cytochrome P450 enzyme, requiring dioxygen, ferredoxin,
      flavodoxin NADP(+)-reductase, and NAD(P)H for activity. StaP on its own converts
      chromopyrrolic acid into three aglycone products, K252c, arcyriaflavin A, and 7
      hydroxy-K252c; in the presence of StaC, K252c is the predominant product, while
      the presence of RebC directs formation of arcyriaflavin A. (18)O-Labeling studies
      indicate that the oxygen(s) of the pyrrolinone and maleimide functionalities of
      the aglycones formed are all derived from dioxygen. This work allowed for the in
      vitro reconstitution of the full biosynthetic pathway from l-tryptophan to the
      staurosporine and rebeccamycin aglycones, K252c and 1,11-dichloroarcyriaflavin A.

PMID- 16967981
TI  - Homogeneously alloyed CdSxSe1-x nanocrystals: synthesis, characterization, and
      composition/size-dependent band gap.
AB  - Alloy nanocrystals provide an additional degree of freedom in selecting desirable
      properties for nanoscale engineering because their physical and optical
      properties depend on both size and composition. We report the pyrolytic synthesis
      of homogeneously alloyed CdS(x)Se(1-x) nanocrystals in all proportions. The
      nanocrystals are characterized using UV-visible absorption spectroscopy,
      transmission electron microscopy, X-ray diffractrometry, and Rutherford
      backscattering spectrometry to determine precisely structure, size, and
      composition. The dependence of band gap on nanocrystal size and composition is
      elucidated, yielding a bowing constant of 0.29, in agreement with bulk values. In
      addition, the morphology of the resultant nanocrystals can be altered by changing
      the reaction conditions, generating structures ranging from homogeneous,
      spherical nanocrystals to one-dimensional gradient nanorods.

PMID- 16967982
TI  - Hydrogen-bonding-mediated anthranilamide homoduplexes. Increasing stability
      through preorganization and iterative arrangement of a simple amide binding site.
AB  - This paper describes the assembly of two new series of self-complementary
      duplexes by making use of amide units, the simplest assembling units of hydrogen
      bonding, as binding sites. All the new monomers possess a rigidified
      anthranilamide skeleton, which is stabilized by intramolecular hydrogen bonding.
      Amide units are iteratively introduced to one side of the preorganized skeletons
      to facilitate the formation of intermolecular hydrogen bonding. Compounds 2 and 3
      bear two and three CONH(2) units, respectively, while 4, 6, and 7 are
      incorporated with two, three, and four AcNH units, respectively. For comparison,
      compound 5, which is similar to 4 but contains one AcNH and one CF(3)CONH unit,
      is also prepared. X-ray diffraction analysis of 2, 4, and 5 revealed homodimeric
      motifs in the solid state which are stabilized by two or more intermolecular
      hydrogen bonds. (1)H NMR investigations in CDCl(3) indicated that all the
      compounds form hydrogen-bonded homoduplexes. Duplexes 3.3, 6.6, and 7.7 are
      highly stable in CDCl(3), with a lower K(assoc) limit of 2.3 x 10(5) M(-1). The
      K(assoc) values of the three duplexes in more polar CDCl(3)/CD(3)CN (9:1, v/v)
      were determined with the (1)H NMR dilution method. The result opens the way for
      the development of new polymeric duplexes of well-ordered structures.

PMID- 16967983
TI  - Born-Haber-Fajans cycle generalized: linear energy relation between molecules,
      crystals, and metals.
AB  - Classical procedures to calculate ion-based lattice potential energies (U(POT))
      assume formal integral charges on the structural units; consequently, poor
      results are anticipated when significant covalency is present. To generalize the
      procedures beyond strictly ionic solids, a method is needed for calculating (i)
      physically reasonable partial charges, delta, and (ii) well-defined and
      consistent asymptotic reference energies corresponding to the separated
      structural components. The problem is here treated for groups 1 and 11
      monohalides and monohydrides, and for the alkali metal elements (with their
      metallic bonds), by using the valence-state atoms-in-molecules (VSAM) model of
      von Szentpaly et al. (J. Phys. Chem. A 2001, 105, 9467). In this model, the Born
      Haber-Fajans reference energy, U(POT), of free ions, M(+) and Y(-), is replaced
      by the energy of charged dissociation products, M(delta)(+) and Y(delta)(-), of
      equalized electronegativity. The partial atomic charge is obtained via the iso
      electronegativity principle, and the asymptotic energy reference of separated
      free ions is lowered by the "ion demotion energy", IDE = -(1)/(2)(1 -
      delta(VS))(I(VS,M) - A(VS,Y)), where delta(VS) is the valence-state partial
      charge and (I(VS,M) - A(VS,Y)) is the difference between the valence-state
      ionization potential and electron affinity of the M and Y atoms producing the
      charged species. A very close linear relation (R = 0.994) is found between the
      molecular valence-state dissociation energy, D(VS), of the VSAM model, and our
      valence-state-based lattice potential energy, U(VS) = U(POT) - (1)/(2)(1 -
      delta(VS))(I(VS,M) - A(VS,Y)) = 1.230D(VS) + 86.4 kJ mol(-)(1). Predictions are
      given for the lattice energy of AuF, the coinage metal monohydrides, and the
      molecular dissociation energy, D(e), of AuI. The coinage metals (Cu, Ag, and Au)
      do not fit into this linear regression because d orbitals are strongly involved
      in their metallic bonding, while s orbitals dominate their homonuclear molecular
      bonding.

PMID- 16967984
TI  - Catalysis of diribonucleoside monophosphate cleavage by water soluble copper(II)
      complexes of calix[4]arene based nitrogen ligands.
AB  - Calix[4]arenes functionalized at the 1,2-, 1,3-, and 1,2,3-positions of the upper
      rim with [12]ane-N(3) ligating units were synthesized, and their bi- and
      trimetallic zinc(II) and copper(II) complexes were investigated as catalysts in
      the cleavage of phosphodiesters as RNA models. The results of comparative kinetic
      studies using monometallic controls indicate that the subunits of all of the
      zinc(II) complexes and of the 1,3-distal bimetallic copper(II) complex 7-Cu(2)
      act as essentially independent monometallic catalysts. The lack of cooperation
      between metal ions in the above complexes is in marked contrast with the behavior
      of the 1,2-vicinal bimetallic copper(II) complex 6-Cu(2), which exhibits high
      catalytic efficiency and high levels of cooperation between metal ions in the
      cleavage of HPNP and of diribonucleoside monophosphates NpN'. A third ligated
      metal ion at the upper rim does not enhance the catalytic efficiency, which
      excludes the simultaneous cooperation in the catalysis of the three metal ions in
      8-Cu(3). Rate accelerations relative to the background brought about by 6-Cu(2)
      and 8-Cu(3) (1.0 mM catalyst, water solution, pH 7.0, 50 degrees C) are on the
      order of 10(4)-fold, largely independent of the nucleobase structure, with the
      exception of the cleavage of diribonucleoside monophosphates in which the
      nucleobase N is uracil, namely UpU and UpG, for which rate enhancements rise to
      10(5)-fold. The rationale for the observed selectivity is discussed in terms of
      deprotonation of the uracil moiety under the reaction conditions and complexation
      of the resulting anion with one of the copper(II) centers.

PMID- 16967985
TI  - Kinetics of CO insertion and acetyl group transfer steps, and a model of the
      acetyl-CoA synthase catalytic mechanism.
AB  - Acetyl-CoA synthase/carbon monoxide dehydrogenase is a Ni-Fe-S-containing enzyme
      that catalyzes the synthesis of acetyl-CoA from CO, CoA, and a methyl group. The
      methyl group is transferred onto the enzyme from a corrinoid-iron-sulfur protein
      (CoFeSP). The kinetics of two steps within the catalytic mechanism were studied
      using the stopped-flow method, including the insertion of CO into a putative
      Ni(2+)-CH(3) bond and the transfer of the resulting acetyl group to CoA. Neither
      step had been studied previously. Reactions were monitored indirectly, starting
      with the methylated intermediate form of the enzyme. Resulting traces were
      analyzed by constructing a simple kinetic model describing the catalytic
      mechanism under reducing conditions. Besides methyl group transfer, CO insertion,
      and acetyl group transfer, fitting to experimental traces required the inclusion
      of an inhibitory step in which CO reversibly bound to the form of the enzyme
      obtained immediately after product release. Global simulation of the reported
      datasets afforded a consistent set of kinetic parameters. The equilibrium
      constant for the overall synthesis of acetyl-CoA was estimated and compared to
      the product of the individual equilibrium constants. Simulations obtained with
      the model duplicated the essential behavior of the enzyme, in terms of the
      variation of activity with [CO], and the time-dependent decay of the NiFeC EPR
      signal upon reaction with CoFeSP. Under standard assay conditions, the model
      suggests that the vast majority of active enzyme molecules in a population should
      be in the methylated form, suggesting that the subsequent catalytic step, namely
      CO insertion, is rate limiting. This conclusion is further supported by a
      sensitivity analysis showing that the rate is most sensitively affected by a
      change in the rate coefficient associated with the CO insertion step.

PMID- 16967986
TI  - Studies of the generation and pericyclic behavior of cyclic pentadienyl
      carbanions. Alkylation reactions as an efficient route to functionalized cis
      bicyclo[3.3.0]octenes.
AB  - Carbolithiation has been studied with alkyllithium reagents in a series of six-
      through nine-membered 3-methylene-1,4-cycloalkadienes, efficiently producing the
      corresponding cyclic pentadienyl carbanions. These pentadienyl anions display
      unique reactivity, depending on ring size. Cyclooctadienyl anions readily undergo
      disrotatory electrocyclization to cis-bicyclo[3.3.0]octenyl systems, which are
      trapped with a variety of electrophiles to stereoselectively provide
      functionalized cis-bicyclo[3.3.0]octenes. The carbolithiation and
      electrocyclization processes are examined using low-temperature (1)H NMR
      experiments. An expedient synthesis of a linear triquinane illustrates this
      methodology. Electrocyclization of the corresponding cyclononadienyl anion
      requires unusually high temperatures (120 degrees C), and computational studies
      provide insights into this change in reactivity. Cycloheptadienyl and
      cyclohexadienyl anions, generated via carbolithiation, provide functionalized
      cycloheptadienes and cyclohexadienes upon electrophilic capture. Trapping
      experiments reveal that the cycloheptadienyl anions are transformed to
      heptatrienyl anions. A series of experiments have been designed to explore
      evidence for the feasibility of equilibration of open and closed anionic systems,
      and these studies report the first isolation of a cis-bicyclo[3.1.0]hexene
      derived from electrocyclization of a cyclohexadienyl carbanion.

PMID- 16967987
TI  - Controlled growth-reversal of catalytic carbon nanotubes under electron-beam
      irradiation.
AB  - The growth of carbon nanotubes from Ni catalysts is reversed and observed in real
      time in a transmission electron microscope, at room temperature. The Ni catalyst
      is found to be Ni3C and remains attached to the nanotube throughout the
      irradiation sequence, indicating that C most likely diffuses on the surface of
      the catalyst to form nanotubes. We calculate the energy barrier for saturating
      the Ni3C (2-13) surface with C to be 0.14 eV, thus providing a low-energy surface
      for the formation of graphene planes.

PMID- 16967988
TI  - Improved subthreshold slope in an InAs nanowire heterostructure field-effect
      transistor.
AB  - An n-type InAs/InAsP heterostructure nanowire field-effect transistor has been
      fabricated and compared with a homogeneous InAs field-effect transistor. For the
      same device geometry, by introduction of the heterostructure, the threshold
      voltage is shifted 4 V, the maximum current on-off ratio is enhanced by a factor
      of 10,000, and the subthreshold swing is lowered by a factor 4 compared to the
      homogeneous transistor. At the same time, the drive current remains constant for
      a fixed gate overdrive. A single nanowire heterostructure transistor has a
      transconductance of 5 muA/V at a low source-drain voltage of 0.3 V. For the
      homogeneous InAs transistor, we deduced a high electron mobility of 1500 cm2/Vs.

PMID- 16967989
TI  - Direct spectroscopic evidence for the formation of one-dimensional wetting wires
      during the growth of InGaAs/GaAs quantum dot chains.
AB  - We report direct spectroscopic evidence for the formation of one-dimensional (1D)
      wetting wires (WWs) during the Stransky-Krastanov growth of InGaAs/GaAs quantum
      dot (QD) chains. The wire-like nature of these 1D WWs was demonstrated by their
      1D density of states and absorption anisotropies from the photoluminescence
      excitation measurements. Two groups of QDs were found sitting on top of these 1D
      WWs and the traditional two-dimensional wetting layers, respectively, with size
      dependent emission polarization anisotropies of ca. 6-25% because of their
      elongated shapes.

PMID- 16967990
TI  - Instability and transport of metal catalyst in the growth of tapered silicon
      nanowires.
AB  - During metal-catalyzed growth of tapered silicon nanowires, or silicon nanocones
      (SiNCs), Au-Si eutectic particles are seen to undergo significant and
      reproducible reductions in their diameters. The reductions are accompanied by the
      transfer of eutectic droplet mass to adjacent, initially metal catalyst-free
      substrates, producing secondary nucleation and growth of SiNCs. Remarkably, the
      catalyst particle diameters on the SiNCs grown on the adjacent substrates are
      strongly correlated with those on the SiNCs grown on the initially Au
      nanoparticle-coated substrate. These post-growth nanoparticle sizes depend on
      temperature and are found to be independent of the initial nanoparticle sizes.
      Our modeling and analysis indicates that the size reduction and mass transfer
      could be explained by electrostatic charge-induced dissociation of the droplet.
      The reduction in size enables the controlled growth of SiNCs with tip sharpnesses
      approaching the atomic scale, indicating that metal-catalyst nanoparticles can
      play an even more dynamic role than previously thought, and suggesting additional
      modes of control of shape, and of nucleation and growth location.

PMID- 16967991
TI  - Regular arrays of monodisperse platinum/erbium disilicide core-shell nanowires
      and nanoparticles on Si(001) via a self-assembled template.
AB  - We have developed a process for fabricating monodisperse noble metal/rare earth
      disilicide core-shell nanoparticles and nanowires in regular arrays on Si(001)
      with a density of 5 x 10(10) / cm2, and over areas > 1 mm2. Pt deposited via
      physical vapor deposition on a self-assembled rare earth disilicide nanowire
      template combined with reactive ion etching produces arrays of nanostructures.
      SEM images demonstrate the ability to select nanowires or nanoparticles as a
      function of Pt coverage. Statistical analysis of images of Pt nanoparticle arrays
      yield a mean feature size of 8 nm with a size variation of +/- 0.9 nm and
      interparticle spacing of approximately 15 nm.

PMID- 16967992
TI  - Quantum dots based probes conjugated to annexin V for photostable apoptosis
      detection and imaging.
AB  - Quantum dots (Qdots) are nanoparticles exhibiting fluorescent properties that can
      be used for cell staining. We present here the development of quantum dots
      conjugated to Annexin V for specific targeting of apoptotic cells, for both
      apoptosis detection and staining of apoptotic "living" cells. For that purpose,
      Qdots Streptavidin Conjugates are coupled to biotinylated Annexin V, a 35-kDa
      protein which specifically recognizes and binds to phosphatidylserine (PS)
      moieties present on the outer membrane of apoptotic cells and not on healthy or
      necrotic cells. By using Annexin V, our Qdots probes are made specific for
      apoptotic cells. Staining of apoptotic cells was checked using fluorescence and
      confocal microscopy techniques and nonfixed cells. It is shown here that Qdots
      are insensitive to bleaching after prolonged exposure as opposed to organic dyes.
      This makes Qdots excellent candidates to continuously follow fast changes
      occurring at the membrane of apoptotic cells and facilitates time-lapse imaging
      as they alleviate any bleaching issue.

PMID- 16967993
TI  - Antibody molecules discriminate between crystalline facets of a gallium arsenide
      semiconductor.
AB  - Seamless integration of biomolecules with manmade materials will most likely rely
      on molecular recognition and specific binding. In the following we show that
      combinatorial antibody libraries, based on the vast repertoire of the human
      immune system, can be harnessed to generate such binders. As a demonstration, we
      isolate antibody fragments that discriminate and bind selectively GaAs (111A)
      facets as opposed to GaAs (100). The isolated antibodies are utilized for
      exclusive localization of a fluorescent dye on (111A) surfaces in a structure
      comprising a mixture of (100) and (111A) surfaces. The potential importance of
      structure rigidity to facet recognition is suggested vis-a-vis published
      experiments with short and longer peptides.

PMID- 16967994
TI  - Dynamics of polymorphic nanostructures: from growth to collapse.
AB  - The deposition of preformed clusters on surfaces offers new possibilities to
      build complex artificial nanostructures, the shape of which depends on the
      cluster size. We describe routes for generating unusual polymorphic nanoislands,
      which constitute unique platforms for exploring instabilities. As coverage
      increases, the constraints accumulated in such nanostructures induce spectacular
      flattening collapse processes, which are not observed when the constraints are
      imposed by the substrate.

PMID- 16967995
TI  - Transparent, conductive, and flexible carbon nanotube films and their application
      in organic light-emitting diodes.
AB  - We have carried out comparative studies on transparent conductive thin films made
      with two kinds of commercial carbon nanotubes: HiPCO and arc-discharge nanotubes.
      These films have been further exploited as hole-injection electrodes for organic
      light-emitting diodes (OLEDs) on both rigid glass and flexible substrates. Our
      experiments reveal that films based on arc-discharge nanotubes are overwhelmingly
      better than HiPCO-nanotube-based films in all of the critical aspects, including
      surface roughness, sheet resistance, and transparency. Further improvement in arc
      discharge nanotube films has been achieved by using PEDOT passivation for better
      surface smoothness and using SOCl2 doping for lower sheet resistance. The
      optimized films show a typical sheet resistance of approximately 160 Omega/
      square at 87% transparency and have been used successfully to make OLEDs with
      high stabilities and long lifetimes.

PMID- 16967996
TI  - Photoconductive characteristics of single-crystal CdS nanoribbons.
AB  - The photoconductive characteristics of CdS single nanoribbons were investigated.
      The device characteristics, including spectral response, light intensity
      response, and time response, were studied systematically. It is found that CdS
      nanoribbon has the response speed substantively faster than those ever reported
      for conventional film and bulk CdS materials and the size of nanoribbons has a
      significant influence on the response speed with smaller CdS nanoribbons showing
      higher response speed. The high photosensitivity and high photoresponse speed are
      attributable to the large surface-to-volume ratio and high single-crystal quality
      of CdS nanoribbons and the reduction of recombination barrier in nanostructures.
      Measurements in a different atmosphere demonstrate that the absorption of ambient
      gas (mainly oxygen) can significantly change the photosensitivity of CdS
      nanoribbons through trapping electrons from the nanoribbons.

PMID- 16967997
TI  - Nanopumping using carbon nanotubes.
AB  - A new "nanopumping" effect consisting of the activation of an axial gas flow
      inside a carbon nanotube by producing Rayleigh traveling waves on the nanotube
      surface is predicted. The driving force for the new effect is the friction
      between the gas particles and the nanotube walls. A molecular dynamics simulation
      of the new effect was carried out showing macroscopic flows of atomic and
      molecular hydrogen and helium gases in a carbon nanotube.

PMID- 16967998
TI  - Electrostatic aggregation and formation of core-shell suprastructures in binary
      mixtures of charged metal nanoparticles.
AB  - Electrostatic aggregation of oppositely charged silver and gold nanoparticles
      leads to the formation of core-shell clusters in which the shell is formed by the
      nanoparticles, which are in excess. Arguments based on Debye screening of
      interactions between like-charged particles help explain why these clusters are
      stable despite possessing net electric charge. The core-shell aggregates exhibit
      unusual optical properties with the resonance absorption of the shell particles
      enhanced by the particles in the core and that of the core suppressed by the
      shell. Experimental UV-vis absorption spectra are faithfully reproduced by Mie
      theory. The modeling allows for estimation of the numbers of particles forming
      the shell and of the shell's effective thickness. These theoretical predictions
      are substantiated by experiments using nanoparticles covered with different
      combinations of charged groups and performed at different values of pH.

PMID- 16967999
TI  - Force-deflection spectroscopy: a new method to determine the Young's modulus of
      nanofilaments.
AB  - We demonstrate the determination of Young's modulus of nanowires or nanotubes via
      a new approach, that is, force-deflection spectroscopy (FDS). An atomic force
      microscope is used to measure force versus deflection (F-D) curves of
      nanofilaments that bridge a trench patterned in a Si substrate. The FD data are
      then fit to the Euler-Bernoulli equation to determine Young's modulus. Our
      approach provides a generic platform from which to study the mechanical and
      piezoelectric properties of a variety of materials at the nanoscale level.
      Young's modulus measurements on ZnS (wurtzite) nanowires are presented to
      demonstrate this technique. We find that the Young's modulus for rectangular
      cross section ZnS nanobelts is 52 +/- 7.0 GPa, about 30% smaller than that
      reported for the bulk.

PMID- 16968000
TI  - Nanoparticle traffic on helical tracks: thermophoretic mass transport through
      carbon nanotubes.
AB  - Using molecular dynamics simulations, we demonstrate and quantify thermophoretic
      motion of solid gold nanoparticles inside carbon nanotubes subject to wall
      temperature gradients ranging from 0.4 to 25 K/nm. For temperature gradients
      below 1 K/nm, we find that the particles move "on tracks" in a predictable
      fashion as they follow unique helical orbits depending on the geometry of the
      carbon nanotubes. These findings markedly advance our knowledge of mass transport
      mechanisms relevant to nanoscale applications.

PMID- 16968001
TI  - Docking of chiral molecules on twisted and helical nanotubes: nanomechanical
      control of catalysis.
AB  - We theoretically demonstrate the possibility of dynamically controlling catalysis
      by nanomechanical means. This novel methodology is based on switching the
      configuration (activity) of catalysts docked on nanoscale surfaces that are
      reversibly deformed. We test the approach by molecular dynamics simulations of an
      organic chiral catalyst that is docked by van der Waals coupling on twisted
      carbon nanotubes. Our results show that its catalytic activity is sharply
      correlated with the direction and amount of the nanotube twist. We also observe a
      small selectivity in docking of chiral molecules on straight helical nanotubes.

PMID- 16968002
TI  - The effects of crowding in dendronized polymers.
AB  - We present a comprehensive numerical study of the effect of degree of
      polymerization, generation of dendron growth, length of dendron tether, and
      dendron grafting density on the conformational statistics of dendronized
      polymers. This class of supramolecular assembly promises to find application in a
      number of nanotechnological devices in which their dimensions and conformations
      are key. We find that the radius of gyration estimates obtained from Brownian
      dynamics simulations yield to a "Flory" scaling argument in the high degree of
      polymerization regime and that these data from a range of topologically distinct
      molecules collapse onto a single curve in this limit. The size of the tethered
      dendrons serve as the key parameter in the scaling theory. Close examination of
      the dendrons also reveals some curious trends. In particular, we observe that as
      the grafting density is increased, spatial packing constraints around the main
      chain backbone force the dendrons further away from the backbone and compress
      them, significantly affecting the spatial distribution and accessibility of
      terminal groups; in contrast to dendrimers, the terminal groups of these
      molecules display a tendency to partition near the surface at high dendron
      grafting densities.

PMID- 16968003
TI  - Highly confined photon transport in subwavelength metallic slot waveguides.
AB  - We report experimental realization of subwavelength slot waveguides that exhibit
      both micrometer-range propagation and high spatial confinement of light.
      Attention is given to rectangular waveguides with a Si3N4 core and Ag cladding;
      core thicknesses of 50-100 nm and widths of 250 nm - 10 microm are explored.
      Propagation lengths of approximately 5lambda are achieved with light confined to
      lateral and transverse dimensions of approximately lambda/5 and approximately
      lambda/2, respectively. This unique combination of light localization and
      propagation is achieved via interacting surface plasmons, which produce short
      modal wavelengths and strong field confinement at each metal/dielectric
      interface.

PMID- 16968004
TI  - Multilayer nanoencapsulation. New approach for immune protection of human
      pancreatic islets.
AB  - Immune protection of artificial tissue by means of pancreatic islet
      microencapsulation is a very ambitious new approach to avoid life-long immune
      suppression. But the success in the utilization of the alginate-beads with
      incorporated islets is unfortunately limited. Some of the problems cannot be
      solved by a two-component system, so polymer encapsulation of the microbeads was
      tested to improve the properties. In the present paper a pure nanoencapsulation
      multilayer approach was tested in order to reduce the size of the capsule and
      possibly apply in the future a multilayer capsule with individual properties in
      each layer or region of the capsule. Different polycations were attached in a
      self-assembly process. The advantage in using the surface charge of islets as
      binding site for the polyions is the guarantee of complete coverage after the
      second layer. Release of insulin was determined to characterize the function of
      the islets after encapsulation as well as the permeability of the capsule.
      Fluorescence microscopy was used to visualize the polyelectrolyte layers. Finally
      by means of an immune assay, the protection capability of the capsule was proved.
      In these first measurements the encapsulation with a multilayer nanocapsule was
      shown to be a possible alternative to the more space-consuming and random islet
      trapping microencapsulation.

PMID- 16968005
TI  - Ultrafast electronic relaxation and charge-carrier localization in CdS/CdSe/CdS
      quantum-dot quantum-well heterostructures.
AB  - The relaxation and localization times of excited electrons in CdS/CdSe/CdS
      colloidal quantum wells were measured using subpicosecond spectroscopy. HRTEM
      analysis and steady-state PL demonstrate a narrow size distribution of 5-6 nm
      epitaxial crystallites. By monitoring the rise time of the stimulated emission as
      a function of pump intensity, the relaxation times of the electron from the CdS
      core into the CdSe well are determined and assigned. Two-component rise times in
      the stimulated emission are attributed to intraband relaxation of carriers
      generated directly within the CdSe well (fast component) and charge transfer of
      core-localized carriers across the CdS/CdSe interface (slow component). This is
      the first reported observation of simultaneous photon absorption in the core and
      well of a quantum-dot heterostructure. With increasing pump intensity, the charge
      transfer channel between the CdS core CdSe well contributes less to the
      stimulated emission signal because of filling and saturation of the CdSe well
      state, making the interfacial charge-transfer component less efficient. The
      interfacial charge-transfer time of the excited electron was determined from the
      slow component of the stimulated emission build-up time and is found to have a
      value of 1.2 ps.

PMID- 16968006
TI  - Interactions in concentric carbon nanotubes: the radius vs the chirality angle
      contributions.
AB  - In multiwall carbon nanotubes in general, and in double wall carbon nanotubes,
      DWCNTs, in particular, the guest-host interactions depend primarily on the
      difference of the nanotubes radii, Deltar. The chirality angle mismatch of the
      two tubes, Deltatheta, also matters since it determines the pattern of pi
      stacking interactions that ultimately is responsible for the shift of graphite
      layers into the so-called A-B structure. Here we calculate the minimum energy
      structures of 198 DWCNTs and construct two functions of Deltar and Deltatheta
      that fit the calculated data. Cross terms exists between Deltar and Deltatheta.
      The shape of the functions is rationalized in simple physical terms and can be
      used to construct minimum energy multiwall nanotubes.

PMID- 16968007
TI  - Defective structure of BN nanotubes: from single vacancies to dislocation lines.
AB  - A combination of electron microscopy and theoretical calculations provides new
      insights into the structure, electronics, and energetics of point defects and
      vacancy lines in BN single-wall nanotubes (SWNT). We show that the point defects
      forming under electron irradiation in the BN SWNTs are primarily divacancies. Due
      to the partially ionic character of the BN bonding, divacancies behave like an
      associated Schottky pair, with a dissociation energy of around 8 eV. Clustering
      of multiple vacancies is energetically favorable and leads to extended defects
      which locally change the nanotube diameter and chirality. Nevertheless these
      defects do not alter significantly the band gap energy, and all of them have
      electronic structure similar to that of BN divacancies. We thus conclude that
      under irradiation BN SWNT may have a very stable alteration of its electronic and
      optical properties.

PMID- 16968008
TI  - Automated formation of lipid-bilayer membranes in a microfluidic device.
AB  - Although membrane channel proteins are important to drug discovery and hold great
      promise as engineered nanopore sensing elements, their widespread application to
      these areas has been limited by difficulties in fabricating planar lipid-bilayer
      membranes. We present a method for forming these sub-5-nm-thick free-standing
      structures based on a self-assembly process driven by solvent extraction in a
      microfluidic channel. This facile automatable process forms high-quality
      membranes able to host channel proteins measurable at single-molecule conductance
      resolution.

PMID- 16968009
TI  - Colloidal synthesis and characterization of tetrapod-shaped magnetic
      nanocrystals.
AB  - Tetrapod-shaped maghemite nanocrystals are synthesized by manipulating the
      decomposition of iron pentacarbonyl in a ternary surfactant mixture under mild
      thermal conditions. Adjustment of the reaction parameters allows for the
      systematic tuning of both the width and the length of the tetrapod arms, which
      grow preferentially along the 111 easy axis direction. Such degree of control
      leads to modulation of the magnetic behavior of the nanocrystals, which evolves
      systematically as their surface magnetization phase and shape anisotropy are
      progressively increased.

PMID- 16968010
TI  - A nanofluidic railroad switch for DNA.
AB  - We present a metamaterial consisting of a two-dimensional, asymmetric lattice of
      crossed nanochannels in fused silica, with channel diameters of 80 nm to 140 nm.
      When DNA is introduced, it is stretched and linearized. We show that the
      asymmetry in channel dimensions gives rise to a preferred direction for DNA
      orientation and a preferred direction for transport under dc electrophoresis.
      Interestingly, the preferred axis of orientation and transport can be switched by
      90 degrees through application of an ac voltage. We explain the results in terms
      of an energy landscape for polyelectrolytes that consists of entropic and
      dielectrophoretic contributions and whose strength and sign can be tuned by
      changing the ac field strength.

PMID- 16968011
TI  - Receptor-ligand-based specific cell adhesion on solid surfaces: hippocampal
      neuronal cells on bilinker functionalized glass.
AB  - Cell adhesion through binding between specific cell membrane receptors and
      corresponding cell-adhesion-molecule (CAM)-coated solid surfaces is examined. The
      morphology of surfaces at various modification steps leading to functionalization
      with cell-binding CAMs is characterized. In one week neuron cultures, enhanced
      growth on surfaces modified with neuron-binding versus astrocyte-binding CAMs is
      observed. However, nonspecific adhesion on a poly-D-lysine-coated positive
      control surface is found to be even higher. Potential reasons and further studies
      needed are discussed.

PMID- 16968012
TI  - Reversible switching of microtubule motility using thermoresponsive polymer
      surfaces.
AB  - We report a novel approach for the dynamic control of gliding microtubule
      motility by external stimuli. Our approach is based on the fabrication of a
      composite surface where functional kinesin motor-molecules are adsorbed onto a
      silicon substrate between surface-grafted polymer chains of thermoresponsive
      poly(N-isopropylacrylamide). By external temperature control between 27 and 35
      degrees C, we demonstrate the reversible landing, gliding, and releasing of motor
      driven microtubules in response to conformational changes of the polymer chains.
      Our method represents a versatile means to control the activity of biomolecular
      motors, and other surface-coupled enzyme systems, in bionanotechnological
      applications.

PMID- 16968014
TI  - Quantum dot encapsulation in viral capsids.
AB  - Incorporation of CdSe/ZnS semiconductor quantum dots (QDs) into viral particles
      provides a new paradigm for the design of intracellular microscopic probes and
      vectors. Several strategies for the incorporation of QDs into viral capsids were
      explored; those functionalized with poly(ethylene glycol) (PEG) can be self
      assembled into viral particles with minimal release of photoreaction products and
      enhanced stability against prolonged irradiation.

PMID- 16968013
TI  - Protease-modulated cellular uptake of quantum dots.
AB  - Quantum dots (QDs) are often cell-impermeable and require transporters to
      facilitate crossing over cell membranes. Here we present a simple and versatile
      method that utilizes enzymes, matrix metalloprotease 2 (MMP-2) and MMP-7, to
      modulate the cellular uptake of QDs. QD-peptide conjugates could be efficiently
      taken up into cells after the MMP treatment. This enzyme-modulated cellular
      uptake of QDs may be applied to other nanoparticles for biological imaging and
      selective drug delivery into tumor cells.

PMID- 16968015
TI  - Dye-sensitized solar cells incorporating a "liquid" hole-transporting material.
AB  - We present the first application of an amorphous "liquid" organic semiconductor
      in an optoelectronic device, demonstrating that it is highly suited for use as a
      hole-transporting material in nanostructured dye-sensitized solar cells. For such
      devices, we obtain power conversion efficiencies of up to 2.4% under simulated
      air mass 1.5 solar spectrum at 100 mWcm(-2), and incident photon-to-electron
      quantum efficiencies in excess of 50%.

PMID- 16968016
TI  - Towards biocompatibility of RE2O3 nanocrystals - water and organic molecules
      chemisorbed on Gd2O3 and Y2O3 nanocrystals studied by quantum-chemical
      computations.
AB  - Nanocrystals of Gd2O3/Y2O3 and their interaction with water, formic acid,
      diethylene glycol (DEG), and tetramethoxy silane (TMOS) have been studied by
      quantum-chemical calculations at the B3LYP level using solvent-coated clusters of
      gadolinia and yttria. Adsorption energies, surface geometries, electronic
      structures, and excitation spectra were calculated. The results concerning
      adsorption strengths and superparamagnetic high-spin states can provide insight
      into the design of molecular-capped RE2O3 nanocrystals to be used in vivo.

PMID- 16968017
TI  - Ultrasensitive chemiresistors based on electrospun TiO2 nanofibers.
AB  - Nanostructured semiconducting metal oxides and particularly single nanowire
      devices offer exceptional gas sensitivity but at the expense of statistical
      variations and excessive noise levels. In this study TiO2/poly(vinyl acetate)
      composite nanofiber mats were directly electrospun onto interdigitated Pt
      electrode arrays, hot pressed at 120 degrees C, and calcined at 450 degrees C.
      This resulted in a novel multiple nanowire network composed of sheaths of 200-500
      nm diameter cores filled with readily gas accessible approximately 10 nm thick
      single-crystal anatase fibrils. TiO2 nanofiber sensors tested for NO2, in dry
      air, exhibited exceptional sensitivity showing with, for example, a 833% increase
      in sensor resistance when exposed to 500 ppb NO2 at 300 degrees C, consistent
      with a detection limit estimated to be well below 1 ppb. Unusual response
      patterns were observed at high NO2 concentrations (> 12.5 ppm), consistent with n
      to p inversion of the surface-trap limited conduction facilitated by the high
      surface-to-volume ratio of this material.

PMID- 16968018
TI  - Signatures of molecular magnetism in single-molecule transport spectroscopy.
AB  - We report single-molecule-transistor measurements on devices incorporating
      magnetic molecules. By studying the electron-tunneling spectrum as a function of
      magnetic field, we are able to identify signatures of magnetic states and their
      associated magnetic anisotropy. A comparison of the data to simulations also
      suggests that sequential electron tunneling may enhance the magnetic relaxation
      of the magnetic molecule.

PMID- 16968019
TI  - Nanoscale patterning on insulating substrates by critical energy electron beam
      lithography.
AB  - This Letter describes a method to generate nanometer scale patterns on insulating
      substrates and wide band gap materials using critical energy electron beam
      lithography. By operating at the critical energy (E2) where a charge balance
      between incoming and outgoing electrons leaves the surface neutral, charge
      induced pattern distortions typically seen in e-beam lithography on insulators
      were practically eliminated. This removes the need for conductive dissipation
      layers or differentially pumped e-beam columns with sophisticated gas delivery
      systems to control charging effects. Using a "scan square" method to find the
      critical energy, sub-100 nm features in 65 nm thick poly(methyl methacrylate) on
      glass were achieved at area doses as low as 10 microC/cm2 at E2 = 1.3 keV. This
      method has potential applications in high-density biochips, flexible electronics,
      and optoelectronics and may improve the fidelity of low voltage e-beam
      lithography for parallel microcolumn arrays.

PMID- 16968020
TI  - Dimensional control of brittle nanoplatelets. A statistical analysis of a thin
      film cracking approach.
AB  - Nanoparticles are essential building blocks for nanotechnology. In this paper we
      demonstrate a novel method to create nanoplatelets by thin film cracking. The
      thickness of the resulting platelets is determined by the film thickness, and
      their aspect ratio is controlled by the total strain and the elastic mismatch
      between substrate and thin film. Platelets can be created from any brittle film
      independently of microstructure and materials class. The feasibility of this
      method is substantiated by a statistical analysis of the fracture process.

PMID- 16968021
TI  - Bioinspired detection of light using a porphyrin-sensitized single-wall nanotube
      field effect transistor.
AB  - Single-wall carbon nanotube (SWNT) field effect transistors (FETs),
      functionalized noncovalently with a zinc porphyrin derivative, were used to
      directly detect a photoinduced electron transfer (PET) within a donor/acceptor
      (D/A) system. We report here that the SWNTs act as the electron donor and the
      porphyrin molecules as the electron acceptor. The magnitude of the PET was
      measured to be a function of both the wavelength and intensity of applied light,
      with a maximum value of 0.37 electrons per porphyrin for light at 420 nm and 100
      W/m2. A complete understanding of the photophysics of this D/A system is
      necessary, as it may form the basis for applications in artificial photosynthesis
      and alternative energy sources such as solar cells.

PMID- 16968022
TI  - Surface plasmons and vibrations of self-assembled silver nanocolumns.
AB  - Optical and vibrational properties of novel self-assembled silver nanocolumns are
      studied experimentally and theoretically. The split of the surface plasmon
      resonance into transverse and longitudinal modes verifies the one-dimensional
      character of the nanocolumns. In this work, we have identified the acoustic
      vibration modes of the nanocolumns using Raman scattering, as spheroid-like modes
      (l = 2, m = +/-2) involving vibrations of the nanocolumns along their minor axes
      and the existence of surface plasmon-vibration coupling mechanisms.

PMID- 16968023
TI  - Neural stimulation with a carbon nanotube microelectrode array.
AB  - We present a novel prototype neural interface using vertically aligned
      multiwalled carbon nanotube (CNT) pillars as microelectrodes. Functionalized
      hydrophilic CNT microelectrodes offer a high charge injection limit (1-1.6
      mC/cm2) without faradic reactions. The first repeated in vitro stimulation of
      hippocampal neurons with CNT electrodes is demonstrated. These results suggest
      that CNTs are capable of providing far safer and more efficacious solutions for
      neural prostheses than previous metal electrode approaches.

PMID- 16968024
TI  - Quantum dots monitor TrkA receptor dynamics in the interior of neural PC12 cells.
AB  - Can quantum dots (QDs) serve as physiologically relevant receptor probes in the
      interior of cells? We directly visualize endocytosis, redistribution, and
      shuttling of QD bound-TrkA receptors to PC12 neural processes and far-reaching
      growth cone tips. Internalized QDs are contained in microtubule-associated
      vesicles and possess transport properties that reflect TrkA receptor dynamics.
      This opens up new possibilities for the development of QD platforms as molecular
      tools to image biochemical signaling and transport cargo in the cell interior.

PMID- 16968025
TI  - Localized surface plasmon resonance spectroscopy of single silver triangular
      nanoprisms.
AB  - The plasmonic properties of single silver triangular nanoprisms are investigated
      using dark-field optical microscopy and spectroscopy. Two distinct localized
      surface plasmon resonances (LSPR) are observed. These are assigned as in-plane
      dipolar and quadrupolar plasmon excitations using electrodynamic modeling based
      on the discrete dipole approximation (DDA). The dipole resonance is found to be
      very intense, and its peak wavelength is extremely sensitive to the height, edge
      length, and tip sharpness of the triangular nanoprism. In contrast, the intensity
      of the quadrupole resonance is much weaker relative to the dipole resonance in
      the single particle spectra than in the ensemble averaged spectrum. Several
      parameters relevant to the chemical sensing properties of these nanoprisms have
      been measured. The dependence of the dipole plasmon resonance on the refractive
      index of the external medium is found to be as high as 205 nm RIU(-1) and the
      plasmon line width as narrow as approximately 0.17 eV. These data lead to a
      sensing figure of merit (FOM), the slope of refractive index sensitivity in eV
      RIU(-1)/line width (eV), as high as 3.3. In addition, the LSPR shift response to
      alkanethiol chain length was found to be linear with a slope of 4.4 nm per CH2
      unit. This is the highest short-range refractive index sensitivity yet measured
      for a nanoparticle.

PMID- 16968026
TI  - "Self-corralling" nanorods under an applied electric field.
AB  - Producing densely packed arrays of nanoscopic anisotropic objects, while
      necessary for applications in photovoltaic and field emission devices, presents
      considerable challenges. Here, we present findings on the phase separation of
      ligand-functionalized nanorods in a polymer matrix under an applied electric
      field. Densely packed hexagonal arrays of nanorods are produced by this method,
      where the rods are oriented in the direction of the applied field. Minimization
      of interfacial energy between the array of nanorods and the surrounding polymer
      serves to corral the nanorods into the densely packed arrays observed. These
      findings carry implications toward advancing organic-inorganic heterojunction
      photovoltaic devices that are expected to benefit from the oriented, densely
      packed ordered arrays of nanorods produced here.

PMID- 16968027
TI  - Realization of a linear germanium nanowire p-n junction.
AB  - Germanium nanowires grown by chemical vapor deposition exhibit a peculiar dopant
      incorporation mechanism. The dopant atoms, such as boron and phosphorus, get
      incorporated through the wire surface, a mechanism which limits the doping
      modulation along the wire length, and therefore the fabrication of more elaborate
      structures that combine both n- and p-type doping. Using a novel device design
      that circumvents these constraints, we demonstrate here a linear Ge nanowire p-n
      junction.

PMID- 16968028
TI  - Cavity QED with diamond nanocrystals and silica microspheres.
AB  - Normal mode splitting is observed in a cavity QED system in which nitrogen
      vacancy centers in diamond nanocrystals are coupled to whispering gallery modes
      in a silica microsphere. The composite nanocrystal-microsphere system takes
      advantage of the exceptional spin properties of nitrogen vacancy centers as well
      as the ultrahigh quality factor of silica microspheres. The observation of the
      normal mode splitting indicates that the dipole optical interaction between the
      relevant nitrogen vacancy center and whispering gallery mode has reached the
      strong coupling regime of cavity QED.

PMID- 16968029
TI  - Controlled electrostatic gating of carbon nanotube FET devices.
AB  - Carbon nanotube transistors are a promising platform for the next generation of
      nonoptical biosensors. However, the exact nature of the biomolecule interactions
      with nanotubes in these devices remains unknown, creating one of the major
      obstacles to their practical use. We assembled alternating layers of oppositely
      charged polyelectrolytes on the carbon nanotube transistors to mimic gating of
      these devices by charged molecules. The devices showed reproducible oscillations
      of the transistor threshold voltage depending on the polarity of the outer
      polymer layer in the multilayer film. This behavior shows excellent agreement
      with the predictions of a simple electrostatic model. Finally, we demonstrate
      that complex interactions of adsorbed species with the device substrate and the
      surrounding electrolyte can produce significant and sometimes unexpected effects
      on the device characteristics.

PMID- 16968030
TI  - Heparin binding nanostructures to promote growth of blood vessels.
AB  - Controlling new blood vessel formation is of interest in regenerative medicine
      and cancer treatment. Heparin, a biopolymer that binds to angiogenic growth
      factors, was used to nucleate the self-assembly of nanostructures from designed
      peptide amphiphile molecules. This process yields rigid nanofibers that display
      heparin chains to orient proteins for cell signaling. In vivo, the nanostructures
      stimulated extensive new blood vessel formation using nanogram amounts of growth
      factor proteins that by themselves did not induce any detectable angiogenesis.

PMID- 16968031
TI  - First-principles study of electrochemical gate-controlled conductance in
      molecular junctions.
AB  - A first-principles computational method is developed to study the electrochemical
      gate-controlled conductance in molecular junctions. It has been applied to a
      single molecular field-effect transistor made by a perylene tetracaboxylic
      diimide molecule connected to gold electrodes and has successfully reproduced the
      experimentally observed huge gate voltage effect on the current. It is found that
      such a significant gain is a result of the large polarization of the molecule
      induced by the huge local electrical field generated by the electrochemical gate.
      The resonant electron tunneling through unoccupied molecular orbitals is shown to
      be the dominant transport process.

PMID- 16968033
TI  - Self-assembled one-dimensional nanostructure arrays.
AB  - A range of proposed devices relies on the electronic, optical or magnetic
      properties of one-dimensional (1D) chains of nanoparticles. Here, well-controlled
      1D arrays have been formed by templating a spherical-morphology block copolymer
      within a narrow groove. Significantly, the domains are distorted into ellipses
      with aspect ratio and major axis orientation controlled by the groove width. This
      technique gives unprecedented control over the period, particle size, aspect
      ratio, and orientation of nanoparticles in 1D arrays, making it valuable for
      creating self-assembled masks for the fabrication of novel devices.

PMID- 16968032
TI  - Complete CO oxidation over Cu2O nanoparticles supported on silica gel.
AB  - We find that nearly monodisperse copper oxide nanoparticles prepared via the
      thermal decomposition of a Cu(I) precursor exhibit exceptional activity toward CO
      oxidation in CO/O2/N2 mixtures. Greater than 99.5% conversion of CO to CO2 could
      be achieved at temperatures less than 250 degrees C for over 12 h. In addition,
      the phase diagram and pathway for CO oxidation on Cu2O (100) is computed by ab
      initio methods and found to be in qualitative agreement with the experimental
      findings.

PMID- 16968034
TI  - Direct evidence for surface plasmon-mediated enhanced light transmission through
      metallic nanohole arrays.
AB  - This paper provides direct evidence for the role of surface plasmons in the
      enhanced optical transmission of light through metallic nanoscale hole arrays.
      Near-field optical images directly confirmed the presence of surface plasmons on
      gold nanohole arrays with interhole spacings larger than the surface plasmon
      wavelength. A simple interference model provides an intuitive explanation of the
      two types of fringe wavelengths observed in the near-field optical images. Far
      field spectroscopy revealed a surface plasmon band that contributed a factor > 8
      to the transmission enhancement. Furthermore, silicon nanohole arrays did not
      exhibit any features in the near-field, which demonstrates that metallic
      materials are necessary for enhanced light transmission through nanohole arrays.

PMID- 16968035
TI  - Optically driven resonance of nanoscale flexural oscillators in liquid.
AB  - We demonstrate the operation of radio frequency nanoscale flexural resonators in
      air and liquid. Doubly clamped string, as well as singly clamped cantilever
      resonators, with nanoscale cross-sectional dimensions and resonant frequencies as
      high as 145 MHz are driven in air as well as liquid with an amplitude modulated
      laser. We show that this laser drive technique can impart sufficient energy to a
      nanoscale resonator to overcome the strong viscous damping present in these
      media, resulting in a mechanical resonance that can be measured by optical
      interference techniques. Resonance in air, isopropyl alcohol, acetone, water, and
      phosphate-buffered saline is demonstrated for devices having cross-sectional
      dimensions close to 100 nm. For operation in air, quality factors as high as 400
      at 145 MHz are demonstrated. In liquid, quality factors ranging from 3 to 10 and
      frequencies ranging from 20 to 100 MHz are observed. These devices, and an all
      optical actuation and detection system, may provide insight into the physics of
      the interaction of nanoscale mechanical structures with their environments,
      greatly extending the viscosity range over which such small flexural resonant
      devices can be operated.

PMID- 16968036
TI  - Selectivity- and size-induced segregation of molecular and nanoscale species in
      microphase-ordered triblock copolymers.
AB  - Microphase-ordered block copolymers serve as model systems to elucidate the
      potential of molecular self-assembly and organic templates to fabricate
      functionalized polymeric materials. Both aspects are related to the incorporation
      of secondary species such as low-molar-mass compounds or nanoparticles within the
      copolymer matrices. Since the resulting properties of such functionalized
      copolymers critically depend on the morphology of the blend or composite, the
      nonrandom distribution of such inclusions within the copolymer matrix must be
      understood. Using a self-consistent field theoretical approach, we quantitatively
      evaluate the segregation and interfacial excess of low-molar-mass and nanoscale
      species in ordered triblock copolymers as functions of block selectivity and
      inclusion size. The predictions are found to agree with the morphology observed
      in a model triblock copolymer/nanoparticle composite, thereby demonstrating the
      generality of this approach. Our results suggest a wide correspondence in the
      structure-forming effect of molecular and nanoscale inclusions that will have
      implications in the design and processing of functional nanostructured polymers.

PMID- 16968037
TI  - Bioengineered flagella protein nanotubes with cysteine loops: self-assembly and
      manipulation in an optical trap.
AB  - An E. coli flagellin protein, termed FliTrx, was investigated for use as a novel
      form of self-assembling protein nanotube. This protein was genetically engineered
      to display constrained peptide loops with a series of different thiol, cationic,
      anionic, and imidazole functional groups. "Cys-loop" thiol variants consisting of
      6 and 12 cysteine residues were isolated in the form of disulfide-linked nanotube
      bundles, a novel nanomaterial. Bundles were characterized by fluorescence
      microscopy, transmission electron microscopy, and optical trapping.

PMID- 16968038
TI  - Manganese-induced growth of GaAs nanowires.
AB  - GaAs nanowires have been grown on SiO2 and GaAs by molecular beam epitaxy using
      manganese as growth catalyst. Transmission electron microscopy shows that the
      wires have a wurtzite-type lattice and that alpha-Mn particles are found at the
      free end of the wires. X-ray absorption fine structure measurements reveal the
      presence of a significant fraction of Mn-As bonds, suggesting Mn diffusion and
      incorporation during wire growth. Transport measurements indicate that the wires
      are p-type, as expected from doping of GaAs with Mn.

PMID- 16968039
TI  - Far field thermal radiation through nanoholes and apertures.
AB  - Thermal radiation through a nanohole or a nanoaperture is calculated in this
      paper. Results show that for aperture size << dominant wavelength of thermally
      excited photons, heat flux deviates significantly from the well-known Planck
      blackbody expression of sigmaT4, where sigma is the Stefan-Boltzmann constant and
      T is the temperature. The heat flux through a nanohole is proportional to T8 and
      a4, where a is the radius of the hole. Finally it is shown that for aT < 10(6),
      where a is expressed in nm and T is expressed in K, radiative heat flux through
      the hole is proportional to T8 and for aT > 10(6) radiative heat flux is equal to
      the Planck blackbody heat flux; i.e., it is proportional to T4.

PMID- 16968040
TI  - Tunable light emission from quantum-confined excitons in TiSi2-catalyzed silicon
      nanowires.
AB  - Visible and near-infrared photoluminescence (PL) at room temperature is reported
      from Si nanowires (NWs) grown by chemical vapor deposition from TiSi2 catalyst
      sites. NWs grown with average diameter of 20 nm were etched and oxidized to thin
      and passivate the wires. The PL emission blue shifted continuously with
      decreasing nanowire diameter. Slowed oxidation was observed for small nanowire
      diameters and provides a high degree of control over the emission wavelength.
      Transmission electron microscopy, PL, and time-resolved PL data are fully
      consistent with quantum confinement of charge carriers in the Si nanowire core
      being the source of luminescence. These light emitting nanowires could find
      application in future CMOS-compatible photonic devices.

PMID- 16968041
TI  - Nanoscale thermal analysis of an energetic material.

PMID- 16968042
TI  - Influences of interfacial resistances on gas transport through carbon nanotube
      membranes.
AB  - Carbon nanotubes have significant promise as gas separation membranes. Gas
      permeation through nanopores involves mass transfer resistances from molecules
      entering and leaving pores (so-called surface resistances) and diffusion within
      the pores. We use molecular simulations to give the first estimates of surface
      resistances for gas transport through nanotubes. For CH4 transport through (20,0)
      carbon nanotubes at 300 K, surface resistances are small for nanotubes 5-10 mum
      in length but can be significant for shorter nanotubes.

PMID- 16968043
TI  - Zero-phonon linewidth in CdSe/ZnS core/shell nanorods.
AB  - High-resolution spectral hole-burning studies of CdSe/ZnS core/shell nanorods
      reveal a sharp zero-phonon line, with a line width dependent on the measurement
      time scale. The zero-phonon line width is attributed to contributions from
      radiative decay, spectral diffusion induced by surface electric field
      fluctuations, and phonon-assisted migration of excitons localized in the
      nanorods. A decoherence rate as small as 4.5 GHz has been observed, when the
      effects of spectral diffusion are suppressed in the spectral hole-burning
      measurement. Comparison between zero-phonon line widths in nanorods and spherical
      nanocrystals also elucidates important differences in the decoherence process
      between the one- and zero-dimensional nanostructures.

PMID- 16968044
TI  - Tuning from thermionic emission to ohmic tunnel contacts via doping in Schottky
      barrier nanotube transistors.
AB  - Electrical power >1 mW is dissipated in semiconducting single-walled carbon
      nanotube devices in a vacuum. After high-power treatment, devices exhibit lower
      on currents and intrinsic, ambipolar behavior with near-ideal thermionic emission
      from Schottky barriers of height one-half the band gap. Upon exposure to air,
      devices recover p-type behavior, with positive threshold and ohmic contacts. The
      air-exposed state cannot be explained by a change in contact work function but
      instead is due to doping of the nanotube.

PMID- 16968045
TI  - Fabrication of high-aspect-ratio metallic nanostructures using nanoskiving.
AB  - This communication describes the fabrication of gold structures (for example,
      rings) with wall thickness of 40 nm, and with high aspect ratios up to 25. This
      technique combines thin-film deposition of metal on a topographically patterned
      epoxy substrate, with nanometer-scale sectioning using a microtome in a plane
      parallel to the patterned substrate. The dimensions of the metal structures are
      determined by the thickness of the metal film and the thickness of the epoxy
      sections. The shape of the resulting nanostructure is defined by the cross
      section of the original template.

PMID- 16968047
TI  - Measurement of inorganic phosphorus in soybeans with near-infrared spectroscopy.
AB  - This study explored the feasibility of near-infrared (NIR) quantitative and
      qualitative models for soybean inorganic phosphorus (Pi), which is complementary
      to phytic acid, a component of nutritional and environmental importance. Spectra,
      consisting of diffuse reflectance (1100-2500 nm) of ground meal and single-bean
      transmittance (600-1900 nm) of whole seed, were collected on 191 recombinant
      inbred soybean lines. Partial least-squares regression models were individually
      developed for soy meal diffuse reflectance, single-bean transmittance, and
      averaged (24 beans/line) whole seed transmittance data. The best performance was
      obtained with diffuse reflectance data, in which the standard errors (rmsd) were
      263 and 248 mg/kg for cross-validation and validation sets, respectively. Model
      accuracy was lower for the 24-bean average transmittance spectra and still lower
      for single beans. Despite the overall poorer modeling ability of Pi with respect
      to the common macronutrient NIR regressions, such as those for protein and oil,
      this technique holds promise for use in breeding programs.

PMID- 16968046
TI  - Core-shell and segmented polymer-metal composite nanostructures.
AB  - Composite nanostructures (approximately 200 nm wide and several micrometers long)
      of metal and polyaniline (PANI) in two new variations of core-shell (PANI-Au) and
      segmented (Au-PANI and Ni-Au-PANI) architectures were fabricated
      electrochemically within anodized aluminum oxide (AAO) membranes. Control over
      the structure of these composites (including the length of the gold shells in the
      core-shell structures) was accomplished by adjusting the time and rate of
      electrodeposition and the pH of the solution from which the materials were grown.
      Exposure of the core-shell structures to oxygen plasma removed the PANI and
      yielded aligned gold nanotubes. In the segmented structures, a self-assembled
      monolayer (SAM) of thioaniline nucleated the growth of PANI on top of metal
      nanorods and acted as an adhesion layer between the metal and PANI components.

PMID- 16968048
TI  - Quantitative determination of pyrethroids, pyrethrins, and piperonyl butoxide in
      surface water by high-resolution gas chromatography/high-resolution mass
      spectrometry.
AB  - A new method for determination of pyrethroids, pyrethrins, and piperonyl butoxide
      (PBO) by high-resolution gas chromatography/high-resolution mass spectrometry
      (HRGC/HRMS) was developed for surface water samples. The method is based on
      sampling 100 L of ambient surface water with a solid phase extraction (SPE)
      technique that uses both wound glass fiber filters for collecting the particulate
      associated chemicals and XAD-2 resin for collecting the dissolved chemicals. The
      method detection limits of the analytes ranged from 0.58 to 8.16 ng/sample, which
      is equivalent to a detection limit range of 0.0058-0.082 ng/L for a 100 L water
      sample collected by the SPE technique. The SPE when coupled with HRGC/HRMS was a
      suitable match for detecting these chemicals at subnanogram per liter ranges that
      are toxicologically significant to aquatic organisms. To confirm the utility of
      this method for environmental applications, pyrethroids and PBO were found at
      subnanogram per liter concentrations in surface water samples collected from five
      tributaries (primarily urban creeks) of the San Francisco Bay, California.

PMID- 16968049
TI  - Analysis of unsaponifiable compounds of edible oils by automated on-line coupling
      reversed-phase liquid chromatography-gas chromatography using the through oven
      transfer adsorption desorption interface.
AB  - An automated method for analysis of unsaponifiable compounds in edible oils is
      presented. The method involves the on-line coupling of reversed-phase liquid
      chromatography and gas chromatography (LC-GC) using the through oven transfer
      adsorption desorption (TOTAD) interface. The oil is injected directly with no
      sample pretreatment step other than filtration. It may also be considered to
      dilute the oil sample. In the LC step, a short C4 column using a methanol/water
      eluent separates analytes from the other components of the oils, which are made
      up of mainly triglycerides. A LC fraction of up to 1.6 mL containing the analytes
      is transferred to GC at a flow rate of 0.1-2 mL/min. The TOTAD interface allows
      solvent venting and the introduction of the analytes into the GC column. The
      proposed fully automated method allows the analysis of different groups of
      compounds (free sterols, tocopherols, squalene, and erythrodiol and uvaol) in one
      chromatographic run or the analysis of these compounds in different groups.
      Sensitivity is more than necessary, and repeatability is good, the CV ranging
      from 3 to 12% for the full analysis.

PMID- 16968050
TI  - NMR, ESI/MS, and MALDI-TOF/MS analysis of pear juice polymeric proanthocyanidins
      with potent free radical scavenging activity.
AB  - The structure of a polymeric proanthocyanidin fraction isolated from pear juice
      was characterized by NMR, ESI/MS, and MALDI-TOF/MS analyses, and its antioxidant
      activity was investigated using the DPPH free radical scavenging method. The
      results obtained from 13C NMR analysis showed the predominance of signals
      representative of procyanidins. Typical signals in the chemical shift region
      between 70 and 90 ppm demonstrated the exclusive presence of epicatechin units.
      The results obtained through negative ESI/MS analysis showed singly and doubly
      charged ions corresponding to the molecular mass of procyanidins with a degree of
      polymerization up to 22. The spectra obtained through MALDI-TOF/MS analysis
      revealed the presence of two series of tannin oligomers. Supporting the
      observations from NMR spectroscopy, the first series consists of well-resolved
      tannin identified as procyanidin polymers units with chain lengths of up to 25. A
      second series of monogalloyl flavan-3-ols polymers with polymerization degree up
      to 25 were also detected. This is the first mass spectrometric evidence
      confirming the existence of galloylated procyanidin oligomers in pear fruits.
      Within each of these oligomers, various signals exist suggesting the presence of
      several oligomeric tannins. The antioxidant properties of the polymeric fraction
      were investigated through reduction of the DPPH free radical, and the results
      obtained showed that the polymeric fraction exhibited a higher antioxidant power
      compared to those of (+)-catechin and B3 procyanidin dimer.

PMID- 16968051
TI  - Small molecule microarrays for drug residue detection in foodstuffs.
AB  - Microarrays have been used as tools for analyzing biological compositions at
      different levels. In this study, we proposed a small molecule microarray (SMM)
      method for detection of three veterinary drug residues, chloramphenicol,
      clenbuterol, and tylosin, in foodstuffs simultaneously and quantitatively. The
      small drug molecules were immobilized on the surface of the modified glass
      slides. Then the mixture of drug corresponding antibodies and standards or
      samples was added to the reaction area. After incubation, the antigen-antibody
      binding was detected using cy5 labeled secondary antibody. The calibration curves
      of the residues were drawn, and they indicated the lowest detection limit the
      linearity range. The detectable concentrations of the three residues are lower
      than the maximum residue levels (MRLs). No cross reactivity was found among the
      three residues. The coefficient of variation of the spot intensities was below 5%
      in a subarray, and below 15% among subarrays. The spike sample test and the
      comparison of detection results by SMMs and ELISA demonstrated the accuracy of
      the proposed SMMs method.

PMID- 16968052
TI  - Occurrence of the free and Peptide forms of pyroglutamic acid in plasma from the
      portal blood of rats that had ingested a wheat gluten hydrolysate containing
      pyroglutamyl peptides.
AB  - In order to determine pyroglutamic acid levels in plasma, we developed a method
      based on precolumn derivatization of the carboxyl group of pyroglutamic acid with
      2-nitrophenylhydrazine. Eight-week-old male SD strain rats were administered 200
      mg of an acidic peptide fraction obtained from a commercial wheat gluten
      hydrolysate containing 0.63 mmol/g pyroglutamyl peptide. After administration,
      significant amounts of free pyroglutamic acid were observed in the ethanol
      soluble fraction of the plasma from the portal vein. In addition, pyroglutamate
      aminopeptidase digestion of the ethanol-soluble fraction liberated significant
      amounts of pyroglutamic acid, which indicated the presence of the pyroglutamyl
      peptide. The presence of the pyroglutamyl peptide in the plasma was further
      confirmed by size exclusion chromatography. The levels of free and peptide forms
      of pyroglutamic acid increased significantly and reached a maximum (approximately
      40 nmol/mL) at 15 and 30 min after administration, respectively.

PMID- 16968053
TI  - Champagne experiences various rhythmical bubbling regimes in a flute.
AB  - Bubble trains are seen rising gracefully from a few points on the glass wall
      (called nucleation sites) whenever champagne is poured into a glass. As time
      passes during the gas-discharging process, the careful observation of some given
      bubble columns reveals that the interbubble distance may change suddenly, thus
      revealing different rhythmical bubbling regimes. Here, it is reported that the
      transitions between the different bubbling regimes of some nucleation sites
      during gas discharging is a process which may be ruled by a strong interaction
      between tiny gas pockets trapped inside the nucleation site and/or also by an
      interaction between the tiny bubbles just blown from the nucleation site.

PMID- 16968054
TI  - Preparation of anti-pefloxacin antibody and development of an indirect
      competitive enzyme-linked immunosorbent assay for detection of pefloxacin residue
      in chicken liver.
AB  - Pefloxacin has been increasingly used in veterinary medicine to treat microbial
      infections. To avoid using a labor-intensive instrumental method to detect the
      residue of pefloxacin in food, a simple and convenient indirect competitive
      enzyme-linked immunosorbent assay method has been developed in this study. The
      antibody generated from immunogen cationized bovine serum albumin-pefloxacin
      showed high sensitivity toward pefloxacin with an IC50 value of 6.7 ppb in buffer
      and was suitable for a screening assay to detect the residue of pefloxacin in
      food products. The antibody has been assessed using rapid enzyme immunoassays to
      exploit its specificity. The antibody prepared shows cross-reactivity with a few
      other (fluoro)quinolones including fleroxacin (116%), enrofloxacin (88%), and
      ofloxacin (10%). The assay measured drug residue in chicken liver spiked with
      pefloxacin with an interassay coefficient of variation of 13.6% or less and an
      intra-assay coefficient of variation of 10.9% or less. The average recovery rates
      at 0.5, 5, 10, 50, and 100 ppb were in the range of 86-106% for interassay and in
      the range of 87-103% for intra-assay, respectively.

PMID- 16968055
TI  - Rapid sample preparation method for LC-MS/MS or GC-MS analysis of acrylamide in
      various food matrices.
AB  - A fast and easy sample preparation procedure for analysis of acrylamide in
      various food matrices was developed and optimized. In its first step, deuterated
      acrylamide internal standard is added to 1 g of homogenized sample together with
      5 mL of hexane, 10 mL of water, 10 mL of acetonitrile, 4 g of MgSO4, and 0.5 g of
      NaCl. Water facilitates the extraction of acrylamide; hexane serves for sample
      defatting; and the salt combination induces separation of water and acetonitrile
      layers and forces the majority of acrylamide into the acetonitrile layer. After
      vigorous shaking of the extraction mixture for 1 min and centrifugation, the
      upper hexane layer is discarded and a 1 mL aliquot of the acetonitrile extract is
      cleaned up by dispersive solid-phase extraction using 50 mg of primary secondary
      amine sorbent and 150 mg of anhydrous MgSO4. The final extract is analyzed either
      by liquid chromatography-tandem mass spectrometry or by gas chromatography-mass
      spectrometry (in positive chemical ionization mode) using the direct sample
      introduction technique for rugged large-volume injection.

PMID- 16968056
TI  - Development of analyses by high-performance liquid chromatography and liquid
      chromatography/tandem mass spectrometry of bilberry (Vaccinium myrtilus)
      anthocyanins in human plasma and urine.
AB  - Anthocyanins are potent antioxidants that may possess chronic disease preventive
      properties. Here, rapid, reliable, and reproducible solid-phase extraction, high
      performance liquid chromatography (HPLC), and mass spectrometry techniques are
      described for the isolation, separation, and identification of anthocyanins in
      human plasma and urine. Recoveries of cyanidin-3-glucoside (C3G) were 91% from
      water, 71% from plasma, and 81% from urine. Intra- and interday variations for
      C3G extraction were 9 and 9.1% in plasma and 7.1 and 9.1% in urine and were less
      than 15% for all anthocyanins from a standardized bilberry extract (mirtoselect).
      Analysis of mirtoselect by HPLC with UV detection produced spectra with 15 peaks
      compatible with anthocyanin components found in mirtoselect within a total run
      time of 15 min. Chromatographic analysis of human urine obtained after an oral
      dose of mirtoselect yielded 19 anthocyanin peaks. Mass spectrometric analysis
      employing multiple reaction monitoring suggests the presence of unchanged
      anthocyanins and anthocyanidin glucuronide metabolites.

PMID- 16968057
TI  - Determination of theanine in commercial tea by liquid chromatography with
      fluorescence and diode array ultraviolet detection.
AB  - Two liquid chromatographic methods that involve precolumn derivatization with o
      phthaladehyde (OPA) and phenylisothiocyanate (PITC) with fluorescence and diode
      array UV detection for the determination of theanine have been developed. The
      chromatographic separations were achieved by reverse-phase high-performance
      liquid chromatography using octadecyl columns and gradient elution. The methods
      were applied to evaluate the theanine content of commercial tea leaves. The
      coefficient of variation of the peak area repeatability for within day (n = 8)
      and between day (n = 8 over 10 days) was lower than 3% for both of the methods.
      The estimated limit of detection (LOD) and limit of quantitation (LOQ) for the
      OPA method was 0.12 and 0.35 microg theanine, respectively. The PITC method was
      500-fold more sensitive with LOD and LOQ values of 0.25 and 0.75 ng,
      respectively. The theanine content of the commercial tea samples varied from 2-5
      mg/g leaf. The overall % recoveries for these methods ranged from 93-99.3. The
      sensitivity and simplicity of the method render them suitable for use in quality
      control laboratories.

PMID- 16968058
TI  - Quality control of commercially available essential oils by means of Raman
      spectroscopy.
AB  - The essential oils of different spices and aroma plants were investigated fast
      and nondestructively by means of Raman spectroscopy. The main ingredients of
      these oils, mostly monoterpenes and phenylpropane derivatives, were identified. A
      hierarchical cluster analysis shows that the oils of the investigated plants
      cluster chemotaxonomically, which means according to their chemical composition
      and not according to their botanical degree of relationship. In addition, cross
      sections of anise seeds were analyzed applying the Raman mapping technique to
      localize and investigate the distribution of the oil in situ.

PMID- 16968059
TI  - Colorimetric characterization for comparative analysis of fungal pigments and
      natural food colorants.
AB  - Exogenous pigments produced by ascomycetous filamentous fungi belonging to the
      genera Penicillium, Epicoccum, and Monascus, preselected based on chemotaxonomic
      knowledge, have been extracted and characterized by quantitative colorimetry. The
      color characteristics of the fungal extracts were compared to water soluble
      natural colorants derived from sources currently in use. The tested fungal
      extracts also included some commercially available Monascus colorants. The a
      values for the fungal extracts were found to be both positive and negative, the b
      values were found to be positive, while the hue angles of the fungal color
      extracts ranged from 40 to 110 indicating the color distribution of fungal
      extracts over the red-orange-yellow region of the CIELAB color space. The fungal
      extracts exhibited additional color hues in the red spectrum and similar hues in
      the yellow spectrum as compared to the reference natural colorants. They were
      also found to be similar or brighter in terms of chroma to some of the reference
      natural colorants. Principal component analysis was performed to group and
      distinguish different colors based on the a and b values. The fungal color
      extracts could be grouped in accordance with the similarity or difference in the
      color to those of the existing natural colorants. The diversity of colors was not
      only found among different fungal genera and/or species but also within the same
      species on changing the media. There was a marked change in the color composition
      of the extracts resulting in relatively different hues. Our results, thus,
      indicate that there exists pigment-producing genera of ascomycetous fungi other
      than Monascus that produce color shades in the red and the yellow spectra in
      addition or similar to reference colorants. These color shades could add to the
      color palette of the natural colorants currently in use. In addition, the
      multivariate approach in distinguishing and classifying the colorants was shown
      to be a very useful tool in colorimetric comparison of colorants.

PMID- 16968060
TI  - Pistachio skin phenolics are destroyed by bleaching resulting in reduced
      antioxidative capacities.
AB  - Pistachio shells split naturally prior to maturity leading to their unique crack
      shell form. Within 24 h of harvest, hull-trapped moisture may cause shell
      staining. The illegal process of bleaching has been used to restore a desirable
      white color to pistachio shells. It is not known whether bleaching adversely
      affects phytochemical levels in pistachios. Therefore, we identified for the
      first time multiple pistachio skin phenolics as quercetin (14.9 microg/g),
      luteolin (10.0 microg/g), eriodictyol (10.2 microg/g), rutin (1.6 microg/g),
      naringenin (1.2 microg/g), apigenin (0.2 microg/g), and the anthocyanins,
      cyanidin-3-galactoside (696 microg/g) and cyanidin-3-glucoside (209 microg/g). We
      investigated the effects of bleaching (0.1-50% hydrogen peroxide) on phenolic
      levels and antioxidative capacities in raw and roasted nuts. Because of their
      flavylium cation structures, anthocyanins were the most sensitive to bleaching.
      Bleaching decreased total anthocyanin levels [mug/g of skins (% hydrogen
      peroxide)]: 905 and 549 (0%); 653 and 145 (0.1%); 111 and 18.4 (5%); 6.1 and 3.2
      (25%); 0 and 0 (50%) for raw and roasted nuts, respectively. Bleaching also
      reduced antioxidative capacity [microM/g of Trolox (% hydrogen peroxide)]: 945
      and 725 (0%); 940 and 472 (0.1%); 930 and 455 (5%); 433 and 370 (25%); 189 and
      173 (50%), for raw and roasted nuts, respectively. Raw nuts preserved phenolic
      levels and antioxidant capacity better than roasted nuts, suggesting contributing
      effects of other substances and/or matrix effects that are destroyed by the
      roasting process. The destruction of bioactive phenolics in pistachio skins may
      negatively impact the potential health benefits arising from pistachio
      consumption.

PMID- 16968061
TI  - Modulation of key elements of the Wnt pathway by apple polyphenols.
AB  - Glycogen synthase kinase-3beta (GSK3beta) is one of the key elements of the Wnt
      pathway involved in the regulation of beta-catenin homeostasis. The inhibition of
      GSK3beta kinase activity might lead to the onset of beta-catenin/TCF/LEF-mediated
      gene transcription, representing a potentially mitogenic stimulus. Apple
      polyphenols have been shown to mediate several biological effects that might be
      of interest with respect to chemoprevention. The objective of the study was to
      elucidate whether apple polyphenols also modulate key elements of the Wnt
      pathway, an effect that might limit the usefulness of these compounds for the
      prevention of carcinogenesis. A polyphenol-rich apple juice extract (AE02) was
      found to effectively inhibit the kinase activity of GSK3beta, immunoprecipitated
      from HT29 cells. Treatment of HT29 cells with AE02 for 24 h resulted in a
      concentration-dependent decrease of the cellular GSK3beta kinase activity. The
      inhibition of the kinase activity in HT29 cells was observed at polyphenol
      concentrations corresponding to the concentration of the constituents in the
      original apple juice. The apple characteristic dihydrochalcone glycoside
      phloridzin was found to be inactive up to 500 muM. The free aglycon phloretin as
      well as the flavonol quercetin effectively inhibited isolated GSK3beta, but did
      not affect the respective kinase activity within HT29 cells. In accordance with
      the inhibition of GSK3beta kinase activity by AE02, treatment of HT29 cells
      resulted in a significant decrease of phosphorylated beta-catenin. However, the
      total intracellular beta-catenin level was also found to be diminished,
      indicating that the interference of the apple constituents with GSK3beta was not
      associated with a stabilization of beta-catenin in HT29 cells. In line with these
      results, TCF/LEF-mediated gene transcription remained unaffected by treatment
      with AE02 as shown in a reporter gene approach. We can assume from the results
      that at consumer-relevant concentrations apple polyphenols do not mediate growth
      stimulating effects in HT29 cells via the Wnt pathway.

PMID- 16968062
TI  - Trichoderma brevicompactum complex: Rich source of novel and recurrent plant
      protective polypeptide antibiotics (peptaibiotics).
AB  - Three strains of Trichoderma brevicompactum and another four that are closely
      related to that species (Trichoderma cf. brevicompactum) were analyzed for the
      formation of polypeptide antibiotics (peptaibiotics) by LC/ESI-MS(n). These
      isolates were selected because of an antagonistic potential against Eutypa
      dieback and Esca disease of grapevine and have not yet been investigated for the
      production of peptide antibiotics. Fully grown cultures on potato dextrose agar
      were extracted with CH2Cl2/MeOH, and this extract was subjected to SPE using C18
      cartridges. The methanolic eluates were analyzed by LC/ESI-MS(n). All strains
      were found to produce membrane-active alamethicins F30. In addition to that,
      novel peptaibiotics were detected, namely, 14 12-residue trichocryptins B, 12 11
      residue trichocryptins A, 19 11-residue trichobrevins A and B, 6 10-residue
      trichoferins, and 17 8-residue trichocompactins. These compounds may partially be
      responsible for the plant-protective action of the producers. Chemotaxonomic
      considerations also indicated the necessity to introduce another new species that
      is closely related to T. brevicompactum.

PMID- 16968063
TI  - Highly efficient preparation of lipophilic hydroxycinnamates by solvent-free
      lipase-catalyzed transesterification.
AB  - Various medium- or long-chain alkyl cinnamates and hydroxycinnamates, including
      oleyl p-coumarate as well as palmityl and oleyl ferulates, were prepared in high
      yield by lipase-catalyzed transesterification of an equimolar mixture of a short
      chain alkyl cinnamate and a fatty alcohol such as lauryl, palmityl, and oleyl
      alcohol under partial vacuum at moderate temperature in the absence of solvents
      and drying agents in direct contact with the reaction mixture. Immobilized lipase
      B from Candida antarctica was the most effective biocatalyst for the various
      transesterification reactions. Transesterification activity of this enzyme was up
      to 56-fold higher than esterification activity for the preparation of medium- and
      long-chain alkyl ferulates. The relative transesterification activities found for
      C. antarctica lipase were of the following order: hydrocinnamate > cinnamate > 4
      hydroxyhydrocinnamate > 3-methoxycinnamate > 2-methoxycinnamate approximately 4
      methoxycinnamate approximately 3-hydroxycinnamate > hydrocaffeate approximately 4
      hydroxycinnamate > ferulate > 2-hydroxycinnamate > caffeate approximately
      sinapate. With respect to the position of the hydroxy substituents at the phenyl
      moiety, the transesterification activity of C. antarctica lipase B increased in
      the order meta > para > ortho. The immobilized lipases from Rhizomucor miehei and
      Thermomyces lanuginosus demonstrated moderate and low transesterification
      activity, respectively. Compounds with inverse chemical structure, that is, 3
      phenylpropyl alkanoates such as 3-(4-hydroxyphenyl)propyl oleate and 3-(3,4
      dimethoxyphenyl)propyl oleate, were obtained by C. antarctica lipase-catalyzed
      transesterification of fatty acid methyl esters with the corresponding 3
      phenylpropan-1-ols in high yield, as well.

PMID- 16968064
TI  - Cranberry phytochemicals: Isolation, structure elucidation, and their
      antiproliferative and antioxidant activities.
AB  - Bioactivity-guided fractionation of cranberries was used to determine the
      chemical identity of bioactive constituents. Twenty compounds were isolated using
      gradient solvent fractionation, silica gel and ODS columns, and preparative RP
      HPLC. Their chemical structures were identified using HR-MS, 1D and 2D NMR, and X
      ray diffraction analysis. Antiproliferative activities of isolated compounds
      against HepG2 human liver cancer and MCF-7 human breast cancer cells were
      evaluated. Among the compounds isolated, ursolic acid, quercetin, and 3,5,7,3',4'
      pentahydroxyflavonol-3-O-beta-D-glucopyranoside showed potent antiproliferative
      activities against HepG2 cell growth, with EC50 values of 87.4 +/- 2.7, 40.9 +/-
      1.1, and 49.2 +/- 4.9 microM, respectively. Ursolic acid, quercetin, and
      3,5,7,3',4'-pentahydroxyflavonol-3-O-beta-D-glucopyranoside showed potent
      inhibitory activity toward the proliferation of MCF-7 cells, with EC50 values of
      11.7 +/- 0.1, 137.5 +/- 2.6, and 23.9 +/- 3.9 microM, respectively. Quercetin,
      3,5,7,3',4'-pentahydroxyflavonol-3-O-beta-D-glucopyranoside, 3,5,7,3',4'
      pentahydroxyflavonol-3-O-beta-D-galactopyranoside, and 3,5,7,3',4'
      pentahydroxyflavonol-3-O-alpha-l-arabinofuranoside showed potent antioxidant
      activities, with EC50 values of approximately 10 microM. These results showed
      cranberry phytochemical extracts have potent antioxidant and antiproliferative
      activities.

PMID- 16968065
TI  - Impact of quercetin and EGCG on key elements of the Wnt pathway in human colon
      carcinoma cells.
AB  - The flavonoids quercetin (QUE) and (-)-epigallocatechin-3-gallate (EGCG) are
      discussed as potential chemopreventive food constituents. Both compounds have
      been shown to affect a spectrum of different cellular signaling pathways.
      Glycogen synthase kinase-3beta (GSK3beta) is one of the key elements of the Wnt
      pathway, governing beta-catenin homeostasis. The inhibition of GSK3 kinase
      activity might lead to the onset of beta-catenin/TCF/LEF-mediated gene
      transcription, representing a potentially mitogenic stimulus. The aim of the
      study was to elucidate whether QUE and EGCG possibly mediate undesired
      proliferative stimuli in human colon carcinoma cells by interference with the Wnt
      pathway. In HT29 cells QUE did not inhibit the activity of GSK3alpha and -beta,
      measured as phosphorylation at Ser21 and Ser9, respectively. In accordance, QUE
      did not substantially affect beta-catenin homeostasis. In a reporter gene assay
      QUE was found to act as a weak inductor of T-cell factor/lymphoid enhancer factor
      (TCF/LEF) mediated luciferase expression, which was, however, not associated with
      a stimulation of cell growth. Treatment of HT29 cells with EGCG led to a potent
      inhibition of GSK3alpha and -beta activity. Subsequently, the amount of
      phosphorylated beta-catenin was diminished in a concentration-dependent manner.
      Concomitantly, the overall amount of beta-catenin was decreased to a similar
      extent, which might result from a downregulation of beta-catenin neogenesis,
      indicated by reduced levels of beta-catenin mRNA. In accordance, no induction of
      TCF/LEF-mediated luciferase expression was observed. In conclusion, the results
      allow the assumption that QUE and EGCG do not mediate proliferative stimuli in
      HT29 cells by interference with key elements of the Wnt pathway.

PMID- 16968066
TI  - Production of mutagenic metabolites by Metarhizium anisopliae.
AB  - NG-391 (1) and NG-393 (2), previously reported from undescribed Fusarium species
      as nerve-cell growth stimulants, were identified from fermentation extracts of
      the entomopathogenic fungus Metarhizium anisopliae. These compounds are 7
      desmethyl analogues of fusarin C and (8Z)-fusarin C, mutagenic toxins from
      Fusarium species that contaminate corn. A mutant strain of M. anisopliae (KOB1-3)
      overproduces 1 and 2 by ca. 10-fold relative to the wild-type strain, ARSEF 2575,
      from which it was derived. Overproduction of these compounds in KOB1-3 imparts a
      yellow pigmentation to the culture medium of the fungus. These compounds were
      inactive at 100 mug/disk in antimicrobial disk diffusion assays. Compound 1 was
      inactive at 100 ppm in a mosquitocidal assay. However, like their fusarin
      analogues, 1 and 2 exhibited potent S9-dependent mutagenic activity in the
      Salmonella mutagenicity test. Discovery of these highly mutagenic mycotoxins in
      M. anisopliae suggests that screening for production of NG-391 and NG-393 in
      strains that are used as biocontrol agents would be a prudent course of action.
      The impact of these findings on the use of M. anisopliae as a biocontrol agent is
      currently unknown and requires further investigation.

PMID- 16968067
TI  - High-performance liquid chromatography with photodiode array detection (HPLC
      DAD)/HPLC-mass spectrometry (MS) profiling of anthocyanins from Andean Mashua
      Tubers (Tropaeolum tuberosum Ruiz and Pavon) and their contribution to the
      overall antioxidant activity.
AB  - Mashua (Tropaeolum tuberosum Ruiz and Pavon), an Andean tuber with high
      antioxidant activity, has sparked interest because of its traditional medicinal
      use. In this study, we evaluated the anthocyanin composition for three purple
      mashua genotypes and their contribution to the overall antioxidant activity of
      the tuber. Mashua anthocyanins, total phenolics, and 2,2'-azinobis(3
      ethylbenzothiazoline-6-sulfonic acid) (ABTS) antioxidant activity ranged from
      45.5 to 131.9 mg of cyanidin 3-glucoside equivalents/100 g fresh weight (FW),
      174.9 to 275.5 mg of gallic acid equivalents/100 g of FW, and 16.2 to 45.7
      micromol of Trolox equivalents/g of FW, respectively. The high-performance liquid
      chromatography with photodiode array detection (HPLC-DAD) and HPLC-electrospray
      ionization tandem mass spectrometry (ESI/MS-MS) profiles revealed the presence of
      11 different anthocyanins. The two major pigments (56.4-73.0% total area range at
      520 nm) were identified as delphinidin 3-glucoside-5-acetylrhamnoside and
      delphinidin 3-sophoroside-5-acetylrhamnoside. Other pigments were delphinidin 3
      glucoside-5-rhamnoside, delphinidin 3-sophoroside-5-rhamnoside, delphinidin 3
      glucoside, cyanidin 3-sophoroside, and cyanidin 3-sophoroside-5-rhamnoside.
      Cyanidin 3-glucoside and cyanidin 3-rutinoside were only found in two genotypes,
      while pelargonidin 3-sophoroside and pelargonidin 3-sophoroside-5-rhamnoside were
      only found in the third one. Anthocyanins from mashua were the major contributors
      to the total ABTS values for only one of the three genotypes, suggesting that
      other phenolics present are playing a major role in the antioxidant power of
      mashua tubers. Results from this study provide important information for the
      Nutraceutical and Functional Food Market for the use of mashua anthocyanins not
      only as a source of natural colorants but also as a source of phytonutrients.

PMID- 16968068
TI  - Gene cloning, expression, and biochemical characterization of a recombinant
      trehalose synthase from Picrophilus torridus in Escherichia coli.
AB  - A trehalose synthase (TSase) gene from a hyperacidophilic, thermophilic archaea,
      Picrophilus torridus, was synthesized using overlap extension PCR and transformed
      into Escherichia coli for expression. The purified recombinant P. torridus TSase
      (PTTS) showed an optimum pH and temperature of 6.0 and 45 degrees C,
      respectively, and the enzyme maintained high activity at pH 5.0 and 60 degrees C.
      Kinetic analysis showed that the enzyme has a 2.5-fold higher catalytic
      efficiency (k(cat)/K(M)) for maltose than for trehalose, indicating maltose as
      the preferred substrate. The maximum conversion rate of maltose into trehalose by
      the enzyme was independent of the substrate concentration, tended to increase at
      lower temperatures, and reached approximately 71% at 20 degrees C. Enzyme
      activity was inhibited by Hg2+, Al3+, and SDS. Five amino acid residues that are
      important for alpha-amylase family enzyme catalysis were shown to be conserved in
      PTTS (Asp203, Glu245, Asp311, His106, and His310) and required for its activity,
      suggesting this enzyme might employ a similar hydrolysis mechanism.

PMID- 16968069
TI  - Expression, purification, and characterization of the maltooligosyltrehalose
      trehalohydrolase from the thermophilic archaeon Sulfolobus solfataricus ATCC
      35092.
AB  - The maltooligosyltrehalose trehalohydrolase (MTHase) mainly cleaves the alpha-1,4
      glucosidic linkage next to the alpha-1,1-linked terminal disaccharide of
      maltooligosyltrehalose to produce trehalose and the maltooligosaccharide with
      lower molecular mass. In this study, the treZ gene encoding MTHase was PCR-cloned
      from Sulfolobus solfataricus ATCC 35092 and then expressed in Escherichia coli. A
      high yield of the active wild-type MTHase, 13300 units/g of wet cells, was
      obtained in the absence of IPTG induction. Wild-type MTHase was purified
      sequentially using heat treatment, nucleic acid precipitation, and ion-exchange
      chromatography. The purified wild-type MTHase showed an apparent optimal pH of 5
      and an optimal temperature at 85 degrees C. The enzyme was stable at pH values
      ranging from 3.5 to 11, and the activity was fully retained after a 2-h
      incubation at 45-85 degrees C. The k(cat) values of the enzyme for hydrolysis of
      maltooligosyltrehaloses with degree of polymerization (DP) 4-7 were 193, 1030,
      1190, and 1230 s(-1), respectively, whereas the k(cat) values for glucose
      formation during hydrolysis of DP 4-7 maltooligosaccharides were 5.49, 17.7,
      18.2, and 6.01 s(-1), respectively. The K(M) values of the enzyme for hydrolysis
      of DP 4-7 maltooligosyltrehaloses and those for maltooligosaccharides are similar
      at the same corresponding DPs. These results suggest that this MTHase could be
      used to produce trehalose at high temperatures.

PMID- 16968070
TI  - Evaluation of binary solvent mixtures for efficient monoacylglycerol production
      by continuous enzymatic glycerolysis.
AB  - This study was aimed at evaluating different binary solvent mixtures for
      efficient industrial monoacylglycerol (MAG) production by enzymatic glycerolysis.
      Of all investigated cases, the binary mixture of tert-butanol:tert-pentanol
      (TB:TP) 80:20 vol % was the most suitable organic medium for continuous enzymatic
      glycerolysis, ensuring high MAG formation in a short time, reasonable solvent
      price, and easy handling during distillation/condensation processing. A minimum
      solvent dosage of 44-54 wt % of the reaction mixture was necessary to achieve
      high MAG yields of 47-56 wt %, within 20 min. The melting and boiling points of
      the TB:TP mixture were estimated to be 7 and 85 degrees C, respectively, using
      thermodynamic models. These predictions were in good agreement with
      experimentally determined values. In spite of the high reaction efficiency in the
      binary TB:TP system, the mixture of glycerol and sunflower oil (containing 97.1%
      triacylglycerol) yielded surprisingly a liquid/liquid phase split behavior even
      at high temperatures (>80 degrees C). This in contrast to thermodynamic model
      calculations suggested full miscibility in all proportions. These findings
      suggest that enhanced reaction efficiency in organic solvent also depends upon
      aspects other than the system homogeneity such as reduced viscosity, reduced mass
      transfer limitations, and the accessibility of the substrate to the active site
      of the enzyme.

PMID- 16968071
TI  - Affinity purification of angiotensin converting enzyme inhibitory peptides using
      immobilized ACE.
AB  - A lung extract rich in angiotensin converting enzyme (ACE) and pure ACE were
      immobilized by reaction with the activated support 4 BCL glyoxyl-agarose. These
      immobilized ACE derivatives were used for purification of ACE inhibitory peptides
      by affinity chromatography. The immobilized lung extract was used to purify
      inhibitory peptides from sunflower and rapeseed protein hydrolysates that had
      been obtained by treatment of protein isolates with alcalase. The ACE binding
      peptides that were retained by the derivatives were specifically released by
      treatment with the ACE inhibitor captopril and further purified by reverse-phase
      C18 HPLC chromatography. Inhibitory peptides with IC50 50 and 150 times lower
      than those of the original sunflower and rapeseed hydrolysates, respectively,
      were obtained. The derivative prepared using pure ACE was used for purification
      of ACE inhibitory peptides from the same type of sunflower protein hydrolysate.
      ACE binding peptides were released from the ACE-agarose derivatives by treatment
      with 1 M NaCl and had an IC50 a little higher than those obtained using
      immobilized extract and elution with captopril. Affinity chromatography
      facilitated the purification of ACE inhibitory peptides and potentially other
      bioactive peptides present in food proteins.

PMID- 16968072
TI  - Optimal formation of hexyl laurate by Lipozyme IM-77 in solvent-free system.
AB  - A medium-chain ester, hexyl laurate, with fruity flavor is primarily used in
      personal care formulations as an important emollient for cosmetic applications.
      To conform to the "natural" interests of consumers, the ability of immobilized
      lipase from Rhizomucor miehei (Lipozyme IM-77) to catalyze the direct
      esterification of hexanol and lauric acid by using a solvent-free system was
      investigated in this study. Response surface methodology (RSM) and four-factor
      five-level central composite rotatable design (CCRD) were employed to evaluate
      the effects of synthesis parameters, such as reaction time (10-50 min),
      temperature (45-85 degrees C), lipase amount (10-30 mg/volume; 0.077-0.231 batch
      acidolysis units of Novo (BAUN), and pH memory (5-9), on percentage molar
      conversion of hexyl laurate by lipase-catalyzed direct esterification. Reaction
      time, temperature, and enzyme amount had significant effects on percent molar
      conversion. On the basis of ridge maximum analysis, the optimum synthesis
      conditions for hexyl laurate were a reaction time of 40.6 min, a temperature of
      58.2 degrees C, an enzyme amount of 25.4 mg/volume (0.196 BAUN), and a pH memory
      of 5.9. The predicted percentage molar conversion of hexyl laurate was 69.7 +/-
      1.4%.

PMID- 16968073
TI  - Phenolic and volatile compounds of extra virgin olive oil (Olea europaea L. Cv.
      Cornicabra) with regard to fruit ripening and irrigation management.
AB  - This study investigated the effect of both the degree of ripening of the olive
      fruit and irrigation management-rain-fed, two different regulated deficit
      irrigations (RDI), the method proposed by the Food and Agriculture Organization
      of the United Nations (known as FAO), and 125 FAO (125% FAO)-on the phenolic and
      volatile composition of Cornicabra virgin olive oils obtained during two crop
      seasons. Secoiridoid phenolic derivatives greatly decreased upon increase of both
      irrigation and ripening, for example, the 3,4-DHPEA-EDA content decreased from
      770 to 450 mg/kg through fruit ripening under rain-fed conditions and from 676 to
      388 mg/kg from rain-fed conditions to FAO irrigation treatment (at a ripeness
      index of approximately 4). Moreover, secoiridoid derivatives of hydroxytyrosol
      decreased more than those of tyrosol. The levels of major volatile components
      decreased in the course of ripening but were higher in irrigated olive oils: for
      example, the E-2-hexenal content ranged between 4.2 and 2.6 mg/kg (expressed as 4
      methyl-2-pentanol) over fruit maturation under rain-fed conditions and between
      8.0 and 3.5 mg/kg under FAO scheduling. It is important to note that where water
      was applied only from the beginning of August (RDI-2), when oil begins to
      accumulate in the fruit, the resulting virgin olive oil presented a phenol and
      volatile profile similar to those of the FAO and 125 FAO methods, but with a
      considerable reduction in the amount of water supplied to the olive orchard.

PMID- 16968074
TI  - Alteration of chemical composition and the oxidative stability of bleached pomace
      olive oil on activated clays.
AB  - This work is a contribution to the study of the bleaching process, which is a
      very important stage in the refining process of vegetable oils and used to reduce
      or convert undesired constituents to harmless ones from fats and oils. The virgin
      olive oil, taken as reference, and the pomace-olive oil were bleached in the
      optimal conditions using Tunisian bleaching earths (South of Tunisia) which were
      activated in our laboratory and compared with commercial clays. It was shown that
      activated Tunisian clays are characterized by a very important adsorptive
      capacity, comparable to that of commercial clays. Also, the physicochemical
      stability of bleached oils was studied. The fatty acid composition (GC), the
      triacylglycerol composition (HPLC), and the oxidative stability (UV spectrometry)
      allowed us to conclude that oils, bleached with the Tunisian activated clays, do
      not undergo considerable physicochemical alterations and remain corresponding to
      the international standards for refined oils for human consumption.

PMID- 16968075
TI  - Discrimination of storage conditions and freshness in virgin olive oil.
AB  - Virgin olive oil samples stored in the light at ambient temperature, in the dark
      at ambient temperature, and at low temperature in the dark for 12 months both
      with and without headspace were separated into recognizable patterns with
      stepwise linear discriminant analysis. The discrimination with variables volatile
      and phenolic compounds, free fatty acid (FFA), peroxide values, K232, and K270
      revealed a departure of stored oil from freshness and showed significant (p <
      0.01) differences between storage conditions. Virgin olive oil stored at low
      temperature had characteristics closest to fresh oil while oil stored in the
      light showed the largest departure from freshness. Parameters that exclusively
      and significantly (p < 0.01) discriminated storage conditions were identified as
      potential markers of the storage condition. In the presence of oxygen, hexanal
      was a marker of storage in the light, FFA was a marker for dark storage, and
      markers of low-temperature storage were acetic acid and pentanal. In the absence
      of oxygen, octane was the marker for storage in the light whereas tyrosol and
      hexanol were markers of virgin olive oil stored in the dark, with no marker
      indicative of low-temperature storage. E-2-Hexenal, K232, and K270 were
      identified as markers of virgin olive oil freshness.

PMID- 16968076
TI  - Kinetics of sucrose crystallization in whey protein films.
AB  - The kinetics of sucrose crystallization in whey protein isolate (WPI) films was
      studied at 25 degrees C in four different relative humidity environments: 23, 33,
      44, and 53%. The effects of protein matrix, crystallization inhibitors, and
      storage environment on the rate constants of sucrose crystallization were
      determined using the Avrami model of crystallization. It was found that a cross
      linked, denatured whey protein (WP) matrix more effectively hindered sucrose
      crystallization than a protein matrix of native WP. The crystallization
      inhibitors tested were lactose, raffinose, modified starch (Purity 69), and
      polyvinylpyrrolidone (Plasdone C15). Raffinose and modified starch were
      determined to be the more effective inhibitors of sucrose crystallization. At
      lower relative humidities (23, 33, and 44%), the cross-linked protein matrix
      played a more important role in sucrose crystallization than the inhibitors. As
      relative humidity increased (53%), the crystallization inhibitors were more
      central to controlling sucrose crystallization in WPI films.

PMID- 16968077
TI  - Analysis of gamma-irradiated melon, pumpkin, and sunflower seeds by electron
      paramagnetic resonance spectroscopy and gas chromatography-mass spectrometry.
AB  - Seeds of melon (Citrullus lanatus var. sp.), pumpkin (Cucurbita moschata), and
      sunflower (Heliantus annus) were gamma-irradiated at 1, 3, 5, and 10 kGy and
      analyzed by electron paramagnetic resonance (EPR) and gas chromatography-mass
      spectrometry (GC-MS) according to EN1787:2000 and EN1785:2003, respectively.
      Distinguishable triplet signals due to the presence of induced cellulose radicals
      were found at 2.0010-2.0047 g in the EPR spectra. The gamma-irradiated radiolytic
      markers of 2-dodecylcyclobutanone (2-DCB) and 2-tetradecylcyclobutanone (2-TCB)
      were identified in all irradiated seed samples. Both the free radicals and the
      alkylcyclobutanones were found to increase with irradiation dose. In general,
      linear relationships between the amount of radicals and irradiation dosage could
      be established. Studies at an ambient temperature (20-25 degrees C) in a humidity
      controlled environment showed a complete disappearance of the cellulosic peaks
      for irradiated samples upon 60 days of storage. Such instability behavior was
      considered to render the usefulness of using EPR alone in the determination of
      irradiated seed samples. On the other hand, 2-DCB and 2-TCB were also found to
      decompose rapidly (>85% loss after 120 days of storage), but the radiolytic
      markers remained quantifiable after 120 days of postirradiation storage. These
      results suggest that GC-MS is a versatile and complimentary technique for the
      confirmation of irradiation treatment to seeds.

PMID- 16968078
TI  - Use of a Plackett-Burman experimental design to examine the impact of extraction
      parameters on yields and compositions of pectins extracted from chicory roots
      (Chicorium intybus L.).
AB  - Chicory root pectin was isolated by acid extraction followed by alcohol
      precipitation. Because the extraction conditions have important effects on the
      features of pectins, an experimental design was used to study the influence of 17
      different extraction parameters on yield and composition of pectin: pH,
      temperature, time of extraction, solid/liquid ratio, and different pretreatments
      of the pulps before extraction. Twenty extractions were conducted and examined
      for their significance on yield and sugar content using the Plackett-Burman
      factorial design. The acid extraction of chicory roots resulted in an average
      yield of 11% containing 86% of sugars. It was found that extraction temperature,
      time, protease pretreatment, water purity, and water washing of pulps
      significantly affected yield and pectin composition with an increase of yield and
      purity of pectin in harsher extraction conditions.

PMID- 16968079
TI  - Detection and quantitation of resveratrol in tomato fruit (Lycopersicon
      esculentum Mill.).
AB  - Resveratrol is a stilbene phytoalexin well-known for its presence in grape, wine,
      and peanut. As a result of its antioxidant and chemopreventative properties, it
      has gained much attention as a functional food ingredient. A gas chromatography
      mass spectrometry method for the detection of resveratrol, its 3-glucopyranoside
      piceid, and the cis isomers of both compounds has been developed and used to
      quantitate the levels of these compounds in the skin of commercially available
      tomato fruit (Lycopersicon esculentum Mill.). The resveratrol concentration
      remains relatively stable during fruit maturation, reaching a maximum
      concentration in the skin of 18.4 +/- 1.6 microg/g dry weight at 4 weeks
      postbreaker. No stilbenes were detected in the flesh of tomato fruit.

PMID- 16968080
TI  - Allergen Ara h 1 occurs in peanuts as a large oligomer rather than as a trimer.
AB  - Ara h 1, a major peanut allergen, is known as a stable trimeric protein.
      Nevertheless, upon purification of native Ara h 1 from peanuts using only size
      exclusion chromatography, the allergen appeared to exist in an oligomeric
      structure, rather than as a trimeric structure. The oligomeric structure was
      independent of the salt concentration applied. Subjecting the allergen to anion
      exchange chromatography induced the allergen to dissociate into trimers. Ammonium
      sulfate precipitation did not bring about any structural changes, whereas
      exposing the allergen to hydrophobic interaction chromatography caused it to
      partly dissociate into trimers, with increasing amounts of trimers at higher
      ionic strengths. The (partial) dissociation into trimers led to a change in the
      tertiary structure of the monomeric subunits of the allergen, with the monomers
      in Ara h 1 oligomers having a more compact tertiary structure compared with the
      monomers in Ara h 1 trimers. As structural characteristics are important for a
      protein's allergenicity, this finding may imply a different allergenicity for Ara
      h 1 than previously described.

PMID- 16968081
TI  - Glyphosate-tolerant alfalfa is compositionally equivalent to conventional alfalfa
      (Medicago sativa L.).
AB  - Glyphosate-tolerant alfalfa (GTA) was developed to withstand over-the-top
      applications of glyphosate, the active ingredient in Roundup agricultural
      herbicides. As a part of the safety assessment, GTA (designated J101 x J163) was
      grown under controlled field conditions at geographically diverse locations
      within the United States during the 2001 and 2003 field seasons along with
      control and other conventional alfalfa varieties for compositional assessment.
      Field trials were conducted using a randomized complete block design with four
      replication blocks at each site. Alfalfa forage was harvested at the late bud to
      early bloom stage from each plot at five field sites in 2001 (establishment year)
      and from four field sites in 2003 (third year of stand). The concentration of
      proximate constituents, fibers, amino acids, coumestrol, and minerals in the
      forage was measured. The results showed that the forage from GTA J101 x J163 is
      compositionally equivalent to forage from the control and conventional alfalfa
      varieties.

PMID- 16968082
TI  - Phenolic acids in berries, fruits, and beverages.
AB  - The contents of soluble and total phenolic acids were analyzed in samples of 29
      berries and berry products, 24 fruits and fruit peels, and 12 beverages.
      Variation of phenolic acids in berries was also studied. Soluble phenolic acids
      were extracted with methanolic acetic acid, and a tentative quantification was
      performed by high-performance liquid chromatography (HPLC). The total phenolic
      acid content was determined by HPLC after alkaline and acid hydrolyses. The
      content of total phenolic acids as aglycones in the above samples varied from 0
      (pear cider) to 103 mg/100 g fresh weight (rowanberry). Besides rowanberry, the
      best phenolic acid sources among berries were chokeberry (96 mg/100 g), blueberry
      (85 mg/100 g), sweet rowanberry (75 mg/100 g), and saskatoon berry (59 mg/100 g).
      Among fruits, the highest contents (28 mg/100 g) were determined in dark plum,
      cherry, and one apple variety (Valkea Kuulas). Coffee (97 mg/100 g) as well as
      green and black teas (30-36 mg/100 g) were the best sources among beverages.
      Caffeic acid dominated in all of these samples except in tea brews. Variation in
      the phenolic acid contents of the berries was either small or moderate.

PMID- 16968083
TI  - A quantitative structure-activity relationship study of herbicidal analogues of
      alpha-hydroxy-substituted 3-benzylidenepyrrolidene-2,4-diones.
AB  - A series of pyrrolidine-2,4-dione and piperidine-2,4-dione derivatives were
      prepared and evaluated for their herbicidal activities where some of these
      compounds exhibited good bioactivity against Echinochloa crus-galli in comparison
      with sulcotrione. Quantitative structure-activity relationship studies were
      performed on these compounds using physicochemical parameters (hydrophobic,
      electronic, and Taft) as independent parameters and herbicidal activity as a
      dependent parameter, where herbicidal activity correlated best (r > 0.8) with
      hydrophobic (pi(o) + pi(p)), steric (Es), STERIMOL (B4), indicator (H(M)), van
      der Waals volume (V), and electronic parameter (sigma(m) + sigma(p)) in this set
      of molecules; the optimum van der Waals volume for R(2) is about 41.8 A3; when B4
      is equal to 3, the target molecule possessed the lowest herbicidal activity.

PMID- 16968084
TI  - Preliminary chemometric study on the use of honey as an environmental marker in
      Galicia (northwestern Spain).
AB  - Thirteen metal elements were determined in 40 honey samples from Galicia with
      different environmental origins: rural, urban, and industrial areas. The data set
      of the honey metallic profiles was studied with a double purpose: first, to make
      a preliminary evaluation of honey as an environmental indicator in Galicia with
      the aim of monitoring pollution and, second, to compare the different
      capabilities of diverse pattern recognition prediction procedures for modeling
      the environmental surrounding of the hive. A certain level of similarity for
      urban and industrial samples was obtained using principal component analysis and
      cluster analysis, whereas significant differences for urban and industrial honeys
      were found in relation to rural honey samples. Different classification rules to
      associate metal content of honeys with their environmental surrounding were
      obtained by chemometric pattern recognition procedures. In general, the
      classification methods developed by neural networks provided better results than
      the traditional pattern recognition procedures. The metal profiles of honey seem
      to provide sufficient information to enable categorization criteria for
      classifying samples according to their environmental surrounding. Thus, honey
      could be a potential pollution indicator for the Galician area.

PMID- 16968085
TI  - Field dissipation and environmental hazard assessment of clomazone, molinate, and
      thiobencarb in Australian rice culture.
AB  - The fates of clomazone [2-(2-chlorophenyl)methyl-4,4-dimethyl-3-isoxazolidinone],
      molinate (S-ethyl hexahydro-1-H-azepine-1-carbothioate), and thiobencarb {S-[(4
      chlorophenyl)methyl]diethylcarbamothioate} applied to rice were studied at two
      locations in New South Wales (Australia). Rates of dissipation (DT50) from
      floodwaters and soils were measured. Dissipation of the three herbicides from
      water and soil can be best explained by a first-order decay process. DT(50)
      values for clomazone, molinate, and thiobencarb were 7.2, 5.1, and 3.5 days,
      respectively, in water and 14.6, 23.9, and >46 days, respectively, in surface
      soil. Maximum measured concentrations of clomazone, molinate, and thiobencarb in
      floodwaters were 202, 1042, and 148 microg/L, respectively, taking 18.4, 26.4,
      and 21.4 days to dissipate to concentrations set to protect aquatic ecosystems. A
      hazard assessment identified clomazone as presenting a low environmental hazard
      while molinate and thiobencarb presented a medium environmental hazard when used
      at registered field rates.

PMID- 16968086
TI  - Soil microbial activity is affected by Roundup WeatherMax and pesticides applied
      to cotton (Gossypium hirsutum).
AB  - Adoption of glyphosate-based weed control systems has led to increased use of the
      herbicide with continued use of additional pesticides. Combinations of pesticides
      may affect soil microbial activity differently than pesticides applied alone.
      Research was conducted to evaluate the influence of glyphosate-based cotton pest
      management systems on soil microbial activity. Soil was treated with commercial
      formulations of trifluralin, aldicarb, and mefenoxam + pentachloronitrobenzene
      (PCNB) with or without glyphosate (applied as Roundup WeatherMax). The soil
      microbial activity was measured by quantifying C and N mineralization. Soil
      microbial biomass was determined using the chloroform fumigation-incubation
      method. Soils treated with glyphosate alone exhibited greater cumulative C
      mineralization 30 days after treatment than all other treatments, which were
      similar to the untreated control. The addition of Roundup WeatherMax reduced C
      mineralization in soils treated with fluometuron, aldicarb, or mefenoxam + PCNB
      formulations. These results indicate that glyphosate-based herbicides alter the
      soil microbial response to other pesticides.

PMID- 16968087
TI  - Aroma extraction dilution analysis of Sauternes wines. Key role of polyfunctional
      thiols.
AB  - The aim of the present work was to investigate Sauternes wine aromas. In all wine
      extracts, polyfunctional thiols were revealed to have a huge impact. A very
      strong bacon-petroleum odor emerged at RI = 845 from a CP-Sil5-CB column. Two
      thiols proved to participate in this perception: 3-methyl-3-sulfanylbutanal and 2
      methylfuran-3-thiol. A strong synergetic effect was evidenced between the two
      compounds. The former, never mentioned before in wines, and not found in the
      musts of this study, is most probably synthesized during fermentation. 3
      Methylbut-2-ene-1-thiol, 3-sulfanylpropyl acetate, 3-sulfanylhexan-1-ol, and 3
      sulfanylheptanal also contribute to the global aromas of Sauternes wines. Among
      other key odorants, the presence of a varietal aroma (alpha-terpineol), sotolon,
      fermentation alcohols (3-methylbutan-1-ol and 2-phenylethanol) and esters (ethyl
      butyrate, ethyl hexanoate, and ethyl isovalerate), carbonyls (trans-non-2-enal
      and beta-damascenone), and wood flavors (guaiacol, vanillin, eugenol, beta-methyl
      gamma-octalactone, and Furaneol) is worth stressing.

PMID- 16968088
TI  - Determination of volatile organic compound patterns characteristic of five
      unifloral honey by solid-phase microextraction-gas chromatography-mass
      spectrometry coupled to chemometrics.
AB  - We report the evaluation of the floral origin of honey by analysis of its
      volatile organic compounds (VOCs) profile, joined with the use of combined
      pattern recognition techniques. Honey samples, from five floral origins, were
      analyzed by headspace solid-phase microextraction-gas chromatography-mass
      spectrometry, selecting 35 VOCs out of the entire profiles, which were analyzed
      by hierarchical cluster analysis (HCA), stepwise discriminant analysis (SDA), and
      K-nearest-neighbor (KNN). Both HCA and SDA were used as exploratory tools to
      select a group of VOCs representing similitude and differences among studied
      origins. Thus, six out of 35 VOCs were selected, verifying their discriminating
      power by KNN, which afforded 93% correct classification. Therefore, we
      drastically reduced the amount of compounds under consideration but kept a good
      differentiation between floral origins. Selected compounds were identified as
      octanal, benzeneacetaldehyde, 1-octanol, 2-methoxyphenol, nonanal, and 2-H-1
      benzopyran-2-one. The analysis of VOC profiles, coupled to HCA, SDA, and KNN,
      provides a feasible alternative to evaluate the botanical source of honey.

PMID- 16968089
TI  - Key odor impact compounds in three yeast extract pastes.
AB  - Three types of yeast extract pastes from two different suppliers were compared.
      Compounds responsible for the key odors include 2-methyl-3-furanthiol, 2-methyl-3
      methyldithiofuran, methional, 1-octen-3-one, dimethyltrisulphide together with a
      number of pyrazines, thiophenes, and aliphatic compounds. The three types of
      yeast extract paste differed in the intensity of their main odors and, in
      particular, those caused by furans, furanthiols, and heterocyclic sulfur
      compounds. Not only do pastes from different suppliers differ in terms of odor
      volatiles, but so do different treatments and batches of yeast extract from one
      supplier. The results suggest that normal variations in the concentrations of
      precursors and processing conditions may cause variations in the flavor of the
      end product.

PMID- 16968090
TI  - Stereoisomeric distribution of 3-mercaptohexan-1-ol and 3-mercaptohexyl acetate
      in dry and sweet white wines made from Vitis vinifera (Var. Sauvignon Blanc and
      Semillon).
AB  - The enantiomeric distribution of 3-mercaptohexan-1-ol (3MH) and 3-mercaptohexyl
      acetate (3MHA) in Vitis vinifera wines was determined by combining two
      techniques: specific purification of volatile thiols from the wines using p
      hydroxymercuribenzoate and separation of the chiral molecules by gas-phase
      chromatography on a cyclodextrin capillary column. The R and S enantiomer ratios
      of these two thiols in dry white Sauvignon blanc and Semillon wines are
      approximately 30:70 for A3MH and 50:50 for 3MH. However, in sweet white wines
      made from grapes affected by "noble rot" due to the development of Botrytis
      cinerea on ripe grapes, the proportion of the R and S forms of 3MH is in the
      vicinity of 30:70. During alcoholic fermentation, a change in the ratio of the
      two enantiomers of 3MH in dry white wines was observed. At the beginning of
      fermentation (around density 1.08), the S form represented over 60%; then, at
      lower density, as fermentation proceeded, the enatiomeric ratio approached 50:50.
      The ratio of the two 3MHA enantiomers remained constant throughout fermentation.
      On the contrary, the distribution of the two 3MH enantiomers changed very little
      during fermentation of the botrytized sweet wines. The perception thresholds for
      the R and S forms of 3MH in hydroalcoholic model solution are similar (50 and 60
      ng/L). These two enantiomers have quite different aromas: The R form is fruitier,
      with a zesty aroma reminiscent of grapefruit, while the S form smells more of
      passion fruit. The perception thresholds of the R and S enantiomers of 3MHA are
      slightly different (9 and 2.5 ng/L). The less odoriferous R form is reminiscent
      of passion fruit, while the S form has a more herbaceous odor of boxwood.

PMID- 16968091
TI  - Relationship between crystallization behavior, microstructure, and macroscopic
      properties in trans containing and trans free coating fats and coatings.
AB  - The objective of this study is to gain further understanding into the
      relationship between crystallization behavior, microstructure, and macroscopic
      properties in coating fats. The isothermal crystallization behavior of two
      coating fats (one trans containing and one trans free) was examined, both as pure
      fats and in coatings, by DSC and microscopy. Furthermore, the hardness of the
      samples was examined after cooling in a water bath at two different temperatures
      and at three different storage times. Both fats seemed to show an alpha-mediated
      beta' crystallization at lower temperatures and a direct beta' crystallization at
      higher temperatures. The trans free coating fat clearly crystallized faster and
      in smaller crystals. The hardness was governed not only by the amount of solid
      fat present in the network but also by the structure of this network. The coating
      matrix components seem to have a pronounced influence on the microstructure and
      thus on the macroscopic properties.

PMID- 16968092
TI  - Effect of methyl jasmonate on phenolics, isothiocyanate, and metabolic enzymes in
      radish sprout (Raphanus sativus L.).
AB  - The effect of spraying exogenous plant hormone methyl jasmonate (MeJA) upon
      radish sprout (Raphanus sativus L.) was investigated in aspects of total phenolic
      content (TPC), isothiocyanate content, antioxidant activity of the radish
      extract, and enzymatic activities of phenylalanine ammonia lyase (PAL) and
      myrosinase. The MeJA treatment significantly increased the TPC that resulted in
      the increased DPPH* (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging
      capacity. In addition, the PAL activity also increased by 60% at 24 h after MeJA
      treatment. However, the same treatment decreased the amount of 4-methylthio-3
      butenylisothiocyanate (MTBITC), a major isothiocyanate in radish sprout and the
      activity of myrosinase, an enzyme related to produce isothiocyanates.

PMID- 16968093
TI  - Comparison of the concentrations of phenolic constituents in cane sugar
      manufacturing products with their antioxidant activities.
AB  - Polyphenol content and free radical scavenging capacity of seven kinds of sugar
      manufacturing products (A sugars, clear juices, syrups, massecuite, and A, B, and
      C molasses) were studied. Seventy-two samples were collected at different stages
      of the process during two sugar harvests from a local sugar factory (Bois-Rouge,
      La Reunion). The total phenolic content of sugar products was determined
      according to the Folin-Ciocalteu assay. Polyphenols of sugar products were
      extracted with ethyl acetate and quantified by LC-UV-ESI-MS during all of the
      process. ABTS and DPPH assays were applied to aqueous solution of sugar products,
      which exhibited interesting free radical scavenging activity. Comparatively,
      ethyl acetate extracts exhibited higher antioxidant activity. Multivariate
      analyses (principal component analysis and canonical discriminant analysis)
      demonstrated a significant correlation between polyphenols and antioxidant
      activity. Moreover, it was observed that the sugar process results in an increase
      of the phenolic content and the free radical scavenging capacity of the different
      products. These products and especially molasses proved to be a rich source of
      natural antioxidants and may represent an interesting alternative to synthetic
      food antioxidants.

PMID- 16968094
TI  - Effects of extraction solvent mixtures on antioxidant activity evaluation and
      their extraction capacity and selectivity for free phenolic compounds in barley
      (Hordeum vulgare L.).
AB  - Four kinds of solvent extracts from three Chinese barley varieties (Ken-3, KA4B,
      and Gan-3) were used to examine the effects of extraction solvent mixtures on
      antioxidant activity evaluation and their extraction capacity and selectivity for
      free phenolic compounds in barley through free radical scavenging activity,
      reducing power and metal chelating activity, and individual and total phenolic
      contents. Results showed that extraction solvent mixtures had significant impacts
      on antioxidant activity estimation, as well as different extraction capacity and
      selectivity for free phenolic compounds in barley. The highest DPPH* and ABTS*+
      scavenging activities and reducing power were found in 80% acetone extracts,
      whereas the strongest *OH scavenging activity, O2*- scavenging activity, and
      metal chelating activity were found in 80% ethanol, 80% methanol, and water
      extracts, respectively. Additionally, 80% acetone showed the highest extraction
      capacity for (+)-catechin and ferulic, caffeic, vanillic, and p-coumaric acids,
      80% methanol for (-)-epicatechin and syringic acid, and water for protocatechuic
      and gallic acids. Furthermore, correlations analysis revealed that TPC, reducing
      power, DPPH* and ABTS*+ scavenging activities were well positively correlated
      with each other (p < 0.01). Thus, for routine screening of barley varieties with
      higher antioxidant activity, 80% acetone was recommended to extract free phenolic
      compounds from barley. DPPH* scavenging activity and ABTS*+ scavenging activity
      or reducing power could be used to assess barley antioxidant activity.

PMID- 16968095
TI  - Effects of conjugated linoleic acid (CLA) isomers on oxygen diffusion
      concentration products in liposomes and phospholipid solutions.
AB  - Conjugated linoleic acids (CLAs) are a group of octadecadienoic acids (18:2) that
      are naturally present in food products and may have beneficial health effects.
      Liposomes and ethanol solutions were prepared by mixing synthetic
      phosphatidylcholines (PCs) with c9,t11-CLA, t10,c12-CLA, and linoleic acid (LA)
      in the sn-2 position into natural PCs from soybean, egg yolk, rat brain, and rat
      heart at 5 mol %. The oxygen diffusion-concentration products were measured using
      electron spin resonance spin-label oximetry methods. Individual synthetic PCs,
      the phospholipid matrix, and the tested lipid systems all exhibited influence on
      oxygen diffusion-concentration products during lipid peroxidation. Incorporating
      5 mol % PC(c9,t11-CLA) into soy and egg yolk PC increased oxygen consumption in
      liposome suspensions while it was decreased in rat heart and brain PCs. On the
      other hand, PC(t10,c12-CLA) increased oxygen consumption in mixtures with egg
      yolk and rat heart PC but decreased it in soybean and rat brain PC. By
      comparison, PC(LA) decreased oxygen consumption in every case. In ethanol
      solutions, all of the synthetic PCs suppressed the capacity to generate peroxide
      radicals in the order of LA > c9,t11-CLA > t10,c12-CLA. In addition, PCs
      containing individual CLA isomers and LA differed in their capacities to react
      with and quench DPPH radicals in both ethanol solution and liposome, suggesting
      differences between CLA isomers and LA in DPPH radical-fatty acid interactions.
      Incorporation of CLA isomers and LA into dimyristyl-PC reduced the phase
      transition temperature from 23.6 to 23.1 and 23.3 degrees C, respectively. The
      results of this study provide evidence that the behavior of CLA isomers differs
      in the microenvironment of membranes possibly due to structural differences that
      affect the permeability of membranes to oxygen and lipid peroxidation.

PMID- 16968096
TI  - Effects of ethylene and 1-methylcyclopropene (1-MCP) on gene expression and
      activity profile of alpha-1,4-glucan-phosphorylase during banana ripening.
AB  - Starch phosphorylases are enzymes that can use starch as substrate, and they are
      supposed to act in both in starch synthesis and degradation. This paper reports
      the effects of ethylene and 1-methylcyclopropene (1-MCP) on the degradation of
      starch and phosphorylase activity and gene expression. The results indicate that
      phosphorylase activity is induced during ripening and that it is associated with
      the onset of starch degradation. The regulation of banana phosphorylase activity
      is mainly dependent on gene expression, and the absence of ethylene perception by
      1-MCP had a positive effect. However, this effect can be precluded by increased
      levels of ethylene, both autocatalytic and exogenous.

PMID- 16968097
TI  - Thermal inactivation of ricin using infant formula as a food matrix.
AB  - Ricin is a potent protein toxin found in the seeds of the castor bean plant,
      Ricinus communis. Ricin specifically and irreversibly inactivates ribosomes,
      promoting cell death by inhibiting protein synthesis. It is composed of a
      ribosome-inactivating enzyme (A-chain) linked to a lectin (B-chain) by a single
      disulfide bond. Several reports indicate that ricin can be detoxified by thermal
      treatment; however, the conditions required for inactivation are not well
      characterized. In addition, little information exists on the thermal stability of
      ricin added to foods. The objective of this work was to determine the effects of
      heat treatments on the detection and toxicity of ricin added to milk- and soy
      based infant formulas. Reconstituted infant formula powders containing 100 mug of
      ricin/mL were heated at 60-90 degrees C for up to 5 h. The heat-treated formulas
      were analyzed by ELISA to determine levels of ricin. The residual cytotoxicity of
      ricin-containing infant formula after heat treatments was determined using
      RAW264.7 mouse macrophage cells. The ELISA and the cytotoxicity assay indicated
      that ricin detection and toxicity decreased with increasing heating times and
      temperatures. Minimal losses in detection and toxicity were found for ricin
      heated at 60 degrees C for 2 h. The half-lives of ricin cytoxic activity in a
      milk-based infant formula at 60, 70, 75, 80, 85, and 90 degrees C were >100, 9.8
      +/- 0.5, 5.8 +/- 0.9, 5.1 +/- 0.7, 3.1 +/- 0.4, and 1.8 +/- 0.2 min,
      respectively; the comparable values for a soy-based infant formula were >100, 16
      +/- 1.6, 8.7 +/- 1.2, 6.9 +/- 1.1, 3.0 +/- 0.4, and 2.0 +/- 0.3 min. ELISA
      detection was a good indicator of the cytotoxicity of heat-treated ricin. The
      results indicate that ricin is a relatively heat stable protein and may remain
      toxic under some food processing conditions.

PMID- 16968098
TI  - Conjugation of sodium caseinate and gum arabic catalyzed by transglutaminase.
AB  - Conjugation of the milk protein sodium caseinate and a protein-containing
      polysaccharide, gum arabic, was achieved through the use of the cross-linking
      enzyme transglutaminase. The extent of conjugation was monitored by size
      exclusion separation coupled with a multiangle laser light scattering detector.
      The elution times of gum arabic solutions incubated with transglutaminase were
      unchanged over time, whereas incubation of sodium caseinate with transglutaminase
      resulted in shorter elution times as reaction time increased, indicating the
      formation of cross-linked caseinate polymers. However, when mixtures of caseinate
      and gum arabic were incubated with transglutaminase, the elution times were
      decreased markedly, indicating conjugation between the protein and
      polysaccharide. The molecular masses of the conjugates increased from
      approximately 950 to 1600 kDa. This method of protein-polysaccharide conjugation
      offers noticeable advantages over previously used methods, and the conjugates
      produced may exhibit unique functional properties.

PMID- 16968099
TI  - Epicatechin carbonyl-trapping reactions in aqueous maillard systems:
      Identification and structural elucidation.
AB  - Recently, our group reported via labeling experiments that epicatechin in
      Maillard reaction aqueous glucose-glycine model systems formed adduct reaction
      products with C2, C3, and C4 sugar fragments. In the current study, we
      investigated the identity of the sugar fragment precursors responsible for adduct
      generation by directly comparing the liquid chromatography-mass spectrometry
      properties of these reported epicatechin (EC)-sugar fragments adducts with those
      generated from reactions consisting of only EC and well-known Maillard-generated
      glucose fragments (i.e., glyoxal, glycolaldehyde, methylglyoxal, glyceraldehyde,
      etc.). The structural properties of an EC-methylglyoxal adduct reaction product
      were also analyzed by NMR. The most likely precursors for the C2, C3, and C4
      sugar moiety of the EC-sugar fragment adducts were identified as glyoxal,
      hydroxyacetone, and erythrose, respectively. 1H NMR analysis of the EC
      methylglyoxal indicated that the analyte underwent rapid
      conformational/constitutional exchange. Using cold temperature (-25 degrees C)
      two-dimensional NMR analyses (heteronuclear multiple bond coherence,
      heteronuclear multiple quantum coherence, and 1H-(1)H correlation spectroscopy),
      the structure of one of the isomers was reported to consist of a covalent linkage
      between the C1 position of the methylglyoxal and either the C6 or the C8 position
      of the EC A ring, presumably generated by hydroxyalkylation and aromatic
      substitution reactions.

PMID- 16968100
TI  - Acidolysis reactions lead to esterification of endogenous tocopherols and
      compromised oxidative stability of modified oils.
AB  - For the first time, a possible mechanism responsible, in part, for the removal of
      endogenous antioxidants through the formation of tocopheryl esters during
      acidolysis reactions is proposed and confirmed. Tocopherols in the oils were
      found to react with carboxylic acids present in the medium, thus leading to the
      formation of tocopheryl esters that do not render any stability to the resultant
      modified oils as they lack any free hydroxyl groups on the phenolic ring of the
      molecule. Tocopheryl oleate, used as a standard, was synthesized through the
      reaction of acyl chloride of oleic acid with alpha-tocopherol (m/z 695.5 as
      evidenced by mass spectrometry). Subsequently, lipase-assisted esterification of
      alpha-, gamma-, and delta-tocopherols with oleic acid was carried out, and
      corresponding tocopheryl esters were isolated. In a real acidolysis reaction
      system involving docosahexaenoic acid single-cell oil and capric acid, high
      performance liquid chromatography-mass spectrometry analysis demonstrated the
      presence of several tocopheryl esters. These included tocopheryl esters of
      myristic acid, namely, alpha-tocopheryl myristate, m/z 641.1, gamma-tocopheryl
      myristate, m/z 627.1, and delta-tocopheryl myristate, m/z 613.1, as well as those
      of palmitic acid, namely, alpha-tocopheryl palmitate, m/z 669.1, gamma-tocopheryl
      palmitate, m/z 655.1, and delta-tocopheryl palmitate, m/z 641.1. The mixture also
      contained different species of tocopheryl oleates, namely, alpha-tocopheryl
      oleate, m/z 695.5, gamma-tocopheryl oleate, m/z 681.1, and delta-tocopheryl
      oleate, m/z 667.2. Esters produced from reactions of docosahexaenoic acid and
      tocopherols were also detected, namely, alpha-tocopheryl docosahexaenoate, m/z
      738.7, and delta-tocopheryl docosahexaenoate, m/z 710.7.

PMID- 16968101
TI  - Antioxidant and antimutagenic properties of Hibiscus tiliaceus L. methanolic
      extract.
AB  - The genus Hibiscus thrives in a variety of climates and produces a diversity of
      natural compounds with bioactive properties. We have studied the chemical
      composition and the in vivo antioxidant properties of Hibiscus tiliaceus L.
      methanolic flower extract, as well as its mutagenic/antimutagenic effects.
      Vitamin E and some stigmasterol derivatives that might confer an antioxidant
      effect to the extract were present. Treatment with this extract protected several
      Saccharomyces cerevisiae strains defective in antioxidant defenses against H2O2
      and t-BOOH cytotoxicities, showing a clear antioxidant activity. The effect is
      the same for all strains used, independent of the antioxidant defense disrupted,
      suggesting that protection may be due to molecules that act as versatile and wide
      spectrum nonenzymatic antioxidants, such as vitamins or phytosterols. The extract
      was not mutagenic in either Salmonella typhimurium or S. cerevisiae and showed a
      significant antimutagenic action against oxidative mutagens in S. cerevisiae.

PMID- 16968102
TI  - Accumulation and extractability of grape skin tannins and anthocyanins at
      different advanced physiological stages.
AB  - Quantitative and qualitative modifications of tannins and anthocyanins in grape
      skin were investigated at different dates of harvest, from berries sorted on the
      basis of their density. Free anthocyanins accumulated until 170 g/L of sugars in
      pulp before undergoing a slight decrease. Changes in anthocyanin composition were
      observed with increasing sugar levels in the pulp that reflected structural
      differences between classes of anthocyanins. The proportion of methoxylated
      anthocyanins continued to increase in the skin as sugar accumulated while the
      proportion of coumaroylated anthocyanins initially increased (up to 200 g/L of
      sugars in the pulp) and then rapidly decreased. In comparison, no major
      quantitative nor qualitative change was observed for tannins, except for a slight
      increase of the mean degree of polymerization. Whatever the physiological stage
      of the pulp, the extraction yield of skin phenolics into hydroalcoholic solution
      for 5 h was lower than 77% for anthocyanins and 38% for proanthocyanidins. For
      both classes of compounds, no clear evolution in these extraction yields could be
      observed as sugars accumulated in pulp (from 162.6 to 275.0 g/L). Nevertheless,
      some structural features within each family of compounds significantly influenced
      extractability, for example, a lower extraction yield for coumaroylated
      anthocyanins and for tannins with a high degree of polymerization. Finally, no
      direct relationship could be found in extraction media between the amounts of all
      red pigments (measured in acidic conditions) and the color intensity at 520 nm
      (measured in wine-like model solutions).

PMID- 16968103
TI  - Effect of protein, nonprotein-soluble components, and lactose concentrations on
      the irreversible thermal denaturation of beta-lactoglobulin and alpha-lactalbumin
      in skim milk.
AB  - The effect of protein, nonprotein-soluble components, and lactose concentrations
      on the irreversible denaturation of beta-lactoglobulin (beta-LG) and alpha
      lactalbumin (alpha-LA) in reconstituted skim milk samples was studied over a wide
      temperature range (75-100 degrees C). The irreversible thermal denaturation of
      beta-LG had a reaction order of 1.5 and that of alpha-LA had a reaction order of
      1.0 in all systems and under all conditions. The rates of irreversible
      denaturation of beta-LG and alpha-LA were markedly dependent upon the composition
      of the milk. At all temperatures, the irreversible denaturations of beta-LG and
      alpha-LA were enhanced at a higher protein concentration and were retarded when
      the nonprotein-soluble components and lactose concentrations were increased. The
      effects of increasing the concentrations of lactose and nonprotein-soluble
      components were interpreted using the preferential hydration theory and allowed
      for the interpretation of the changes in the denaturations of beta-LG and alpha
      LA when the milk total solids concentration was increased.

PMID- 16968104
TI  - Extraction, detection, and quantification of flavano-ellagitannins and
      ethylvescalagin in a Bordeaux red wine aged in oak barrels.
AB  - An extraction procedure and an analytical method have been developed to detect
      and quantify for the first time a series of ellagitannin derivatives formed in
      wine during aging in oak barrels. The method involves a preliminary purification
      step on XAD7 HP resin followed by a second purification step on TSK 40 HW gel.
      The resulting extract is analyzed for compound identification and quantitative
      determination by high-performance liquid chromatography-electrospray ionization
      mass spectrometry in single ion recording mode. Reference compounds, which are
      accessible through hemisynthesis from the oak C-glycosidic ellagitannin
      vescalagin, were used to build calibration curves, and chlorogenic acid was
      selected as an internal standard. This method enabled us to estimate the content
      of four flavano-ellagitannins and that of another newly identified wine
      polyphenol, beta-1-O-ethylvescalagin, in a Bordeaux red wine aged for 18 months
      in oak barrels. All five ellagitannin derivatives are derived from the
      nucleophilic substitution reaction of vescalagin with the grape flavan-3-ols
      catechin and epicatechin or ethanol.

PMID- 16968105
TI  - Total antioxidant activity and fiber content of select Florida-grown tropical
      fruits.
AB  - Fourteen tropical fruits from south Florida (red guava, white guava, carambola,
      red pitaya (red dragon), white pitaya (white dragon), mamey sapote, sapodilla,
      lychee, longan, green mango, ripe mango, green papaya, and ripe papaya) were
      evaluated for antioxidant activity, total soluble phenolics (TSP), total ascorbic
      acid (TAA), total dietary fiber (TDF), and pectin. ORAC (oxygen radical
      absorbance capacity) and DPPH (1,1-diphenyl-2-picrylhydrazyl, radical scavenging
      activity) assays were used to determine antioxidant activity. The TSP, ORAC, and
      DPPH ranged from 205.4 to 2316.7 g gallic acid equiv/g puree, <0.1 to 16.7
      micromol Trolox equiv/g puree, and 2.1 to 620.2 microg gallic acid equiv/g puree,
      respectively. The TAA, TDF, and pectin ranged from 7.5 to 188.8 mg/100 g, 0.9 to
      7.2 g/100 g, and 0.20 to 1.04 g/100 g, respectively. The antioxidant activities,
      TSP, TAA, TDF, and pectin were influenced by cultivar (papaya, guava, and dragon
      fruit) and ripening stage (papaya and/or mango). Antioxidant activity showed high
      correlations with levels of TSP compounds (r = 0.96) but low correlations with
      levels of ascorbic acid (r = 0.35 and 0.23 for ORAC and DPPH data, respectively).
      The antioxidant activities evaluated by both ORAC and DPPH showed similar trends
      where red guava and carambola exhibited the highest and sapodilla and green
      papaya exhibited the lowest levels. Guava and mamey sapote exhibited the highest
      TDF and pectin levels. Many of the tropical fruits were shown to contain an
      abundance of hydrolyzable tannins, ellagic acid conjugates, and flavone
      glycosides. Preliminary descriptions are given of the phenols in red/white pitaya
      (dragonfruit), lychee, and mamey sapote, these fruit being thus far
      uncharacterized in the literature.

PMID- 16968106
TI  - Absorption of flavonols derived from sea buckthorn (Hippophae rhamnoides L.) and
      their effect on emerging risk factors for cardiovascular disease in humans.
AB  - Sea buckthorn (Hippophae rhamnoides L.) is a rich source of flavonols, especially
      isorhamnetin. Most prospective cohort studies have indicated some degree of
      inverse association between flavonoid intake and coronary heart disease. Animal
      and human studies suggest that sea buckthorn flavonoids may scavenge free
      radicals, lower blood viscosity, and enhance cardiac function. The effects of
      flavonol aglycones derived from sea buckthorn on the risk factors of
      cardiovascular disease as well as their absorption were studied in humans. The
      flavonols, ingested with oatmeal porridge, did not have a significant effect on
      the levels of oxidized low-density lipoprotein, C-reactive protein, and
      homocysteine, on the plasma antioxidant potential, or on the paraoxonase
      activity. Flavonols at two dosages in oatmeal porridge were rapidly absorbed, and
      a relatively small amount of sea buckthorn oil added to the porridge seemed to
      have increased the bioavailability of sea buckthorn flavonols consumed at the
      higher dose.

PMID- 16968108
TI  - Bilberry adulteration using the food dye amaranth.
AB  - Vaccinium myrtillus or bilberry fruit is a commonly used herbal product. The
      usual method of determining the anthocyanin content is a single-wavelength
      spectrophotometric assay. Using this method, anthocyanin levels of two extracts
      were found to be 25% as claimed by the manufacturers. When high-performance
      liquid chromatography (HPLC) was used, however, one extract was found to contain
      9% anthocyanins probably not derived from V. myrtillus but from an adulterant.
      This adulterant was subsequently identified, using HPLC, mass spectroscopy, and
      nuclear magnetic resonance, as amaranth, that is, 3-hydroxy-4-[(4-sulfo-1
      naphthalenyl)azo]-2,7-naphthalenedisulfonic acid trisodium salt-a synthetic dark
      red sulfonic acid based naphthylazo dye. As described in this study, if
      deliberate adulteration occurs in an extract, a single-wavelength
      spectrophotometric assay is inadequate to accurately determine the levels of
      compounds such as anthocyanins. Detection of deliberate adulteration in
      commercial samples thus requires the use of alternative, more sophisticated,
      methods of analysis such as HPLC with photodiode array detection as a minimum.

PMID- 16968107
TI  - Analysis of acrylamide in green tea by gas chromatography-mass spectrometry.
AB  - Optimization of the solid-phase extraction cleanup procedure enabled the GC-MS
      analysis of acrylamide in tea samples without the interference of bromination by
      tea catechins. Although polyvinylpolypyrrolidone (PVPP) is available for removing
      tea catechins from tea extract, the peaks derived from PVPP had the same
      retention time as brominated acrylamide in mass chromatograms obtained by GC-MS.
      A considerable amount of acrylamide was formed at roasting temperatures of > or
      =120 degrees C; the highest acrylamide level was observed when tea samples were
      roasted at 180 degrees C for 10 min. Higher temperatures and longer processing
      times caused a decrease in the acrylamide content. Furthermore, an analysis of 82
      tea samples showed that rather than the reducing sugar content, the asparagine
      content in tea leaves was a significant factor related to acrylamide formation in
      roasted products. The acrylamide level in roasted tea products was controlled by
      asparagine in the presence of reducing sugars.

PMID- 16968109
TI  - Maize ear rot and moniliformin contamination by cryptic species of Fusarium
      subglutinans.
AB  - Fusarium subglutinans causes maize ear rot and contaminates grain with the
      mycotoxin moniliformin. Previous DNA sequence analysis divided F. subglutinans
      from maize into two cryptic species, designated groups 1 and 2. Here, it was
      determined whether the two groups differ in the agriculturally important traits
      of virulence on maize and moniliformin production in planta. Thirty-seven strains
      from U.S. maize were assigned to groups 1 and 2 by DNA sequence analysis. In
      field tests, all strains were highly virulent on maize inbred B73 and four maize
      hybrids. In planta, 82% of group 1 strains and 25% of group 2 strains produced
      high levels (100-1500 microg/g) of moniliformin. All group 2 strains from more
      northern states produced little or no moniliformin (0-5 microg/g). These data
      indicate that moniliformin production is highly variable in F. subglutinans from
      U.S. maize and that production may not be required for the fungus to cause maize
      ear rot.

PMID- 16968110
TI  - Influence of lupin (Lupinus luteus L. cv. 4492 and Lupinus angustifolius L. var.
      zapaton) and fenugreek (Trigonella foenum-graecum L.) germination on microbial
      population and biogenic amines.
AB  - Microbial population and bioactive amine profile and levels of two lupin species
      (Lupinus luteus L. cv. 4492 and Lupinus angustifolius L. var. zapaton) and
      fenugreek (Trigonella foenum-graecum L.) seeds as affected by germination were
      investigated. Microbial population increased considerably mainly in the first
      stage of germination (2 days), then small changes in bacterial numbers were
      observed up to 5 days to levels between 7.8 and 8.9 log colony-forming units/g.
      Microorganisms belonging to the Enterobacteriaceae family were dominant for the
      legumes tested. Ungerminated legume seeds contained putrescine, cadaverine,
      histamine, tyramine, spermidine, and spermine. Bioactive amine levels found in
      fenugreek seeds were between 3- and 4-fold higher than those found in lupin
      seeds. The highest total amine levels were found in fenugreek seeds [162 mg/kg of
      dry weight (dw)], followed by L. angustifolius var. zapaton seeds (84 mg/kg of
      dw) and, finally, L. luteus cv. 4492 (46 mg/kg of dw) seeds. The concentration of
      individual amines showed a gradual rising trend during the germination period in
      all tested sprouts, reaching levels >3 times higher than those found in
      ungerminated seeds. After 5 days of germination, the fenugreek sprouts contained
      the highest amount of total bioactive amines. Tyramine was the predominant amine
      in both lupin varieties, whereas cadaverine was the main bioactive amine detected
      in fenugreek. The results of this work thus indicated that microbial population
      and biogenic amine levels in the studied lupin and fenugreek sprouts are not a
      risk for healthy consumers or for individuals with restricted activity of
      detoxification enzymes.

PMID- 16968111
TI  - Ochratoxin a contents in wine: comparison of organically and conventionally
      produced products.
AB  - Ochratoxin A (OTA) content was determined in 44 organically and conventionally
      produced wines originating from different geographical regions. Wine samples were
      extracted using a series of C18 and mixed-bed solid-phase cartridges and analyzed
      by HPLC with fluorescence detection. The identity of the mycotoxin was confirmed
      using liquid chromatography-tandem mass spectrometry. Recoveries were in excess
      of 90%, intraday precisions were better than 6%, and the interday variation was
      15%. Limit of detection was 0.05 microg/L (HPLC). All sampled wines contained OTA
      below the level permitted by the European Union of 2 microg/L, ranging from not
      detectable (nd) to 0.75 microg/L for red wines (n = 26), from nd to 0.092
      microg/L for rose wines (n = 2), and from nd to 0.22 microg/L for white wines (n
      = 16). The concentration of OTA in organically produced wines (nd to 0.72
      microg/L, median 0.092 microg/L, n = 19) was not significantly different from
      that in conventional products (nd to 0.75 microg/L, median 0.066 microg/L, n =
      25) as assessed by a Mann-Whitney statistical test (p = 0.54).

PMID- 16968113
TI  - The distinct signaling mechanisms of microbial sensory rhodopsins in Archaea,
      Eubacteria and Eukarya.
AB  - Most of the known archaeal-type microbial rhodopsins are retinal-binding ion
      transporters, such as bacteriorhodopsin (BR) and proteorhodopsin (PR). Their
      identification is the result of extensive studies of their photochemical and
      biophysical properties. The cells containing these pigments, however, use other
      microbial rhodopsins as photosensors to monitor environmental light signals. From
      the early studies of sensory rhodopsin I (HsSRI) in Halobacterium salinarum and
      sensory rhodopsin II (NpSRII) in Natronomonas pharaonis, we now know that several
      microbial sensory rhodopsins in the other major domain of life relay information
      on light intensity and quality to the cell. Three of the most studied
      photosensory transduction mechanisms of these microbial rhodopsins are dealt with
      in this review. We discuss recent progress in the understanding of genomic
      organization, photochemical properties and photosignaling mechanisms with respect
      to biological function.

PMID- 16968114
TI  - Photochemistry of organic iron(III) complexing ligands in oceanic systems.
AB  - Iron is a limiting nutrient for primary production in marine systems, and
      photochemical processes play a significant role in the upper ocean biogeochemical
      cycling of this key element. In recent years, progress has been made toward
      understanding the role of biologically produced organic ligands in controlling
      the speciation and photochemical redox cycling of iron in ocean surface waters.
      Most (>99%) of the dissolved iron in seawater is now known to be associated with
      strong organic ligands. New data concerning the structure and photochemical
      reactivity of strong Fe(III) binding ligands (siderophores) produced by pelagic
      marine bacteria suggest that direct photolysis via ligand-to-metal charge
      transfer reactions may be an important mechanism for the production of reduced,
      biologically available iron (Fe[II]) in surface waters. Questions remain,
      however, about the importance of these processes relative to secondary
      photochemical reactions with photochemically produced radical species, such as
      superoxide (O2-). The mechanism of superoxide-mediated reduction of Fe(III) in
      the presence of strong Fe(III) organic ligands is also open to debate. This
      review highlights recent findings, including both model ligand studies and
      experimentallobservational studies of the natural seawater ligand pool.

PMID- 16968115
TI  - Empirical evidence for the effect of airline travel on inter-regional influenza
      spread in the United States.
AB  - BACKGROUND: The influence of air travel on influenza spread has been the subject
      of numerous investigations using simulation, but very little empirical evidence
      has been provided. Understanding the role of airline travel in large-scale
      influenza spread is especially important given the mounting threat of an
      influenza pandemic. Several recent simulation studies have concluded that air
      travel restrictions may not have a significant impact on the course of a
      pandemic. Here, we assess, with empirical data, the role of airline volume on the
      yearly inter-regional spread of influenza in the United States. METHODS AND
      FINDINGS: We measured rate of inter-regional spread and timing of influenza in
      the United States for nine seasons, from 1996 to 2005 using weekly influenza and
      pneumonia mortality from the Centers for Disease Control and Prevention.
      Seasonality was characterized by band-pass filtering. We found that domestic
      airline travel volume in November (mostly surrounding the Thanksgiving holiday)
      predicts the rate of influenza spread (r(2) = 0.60; p = 0.014). We also found
      that international airline travel influences the timing of influenza mortality
      (r(2) = 0.59; p = 0.016). The flight ban in the US after the terrorist attack on
      September 11, 2001, and the subsequent depression of the air travel market,
      provided a natural experiment for the evaluation of flight restrictions; the
      decrease in air travel was associated with a delayed and prolonged influenza
      season. CONCLUSIONS: We provide the first empirical evidence for the role of
      airline travel in long-range dissemination of influenza. Our results suggest an
      important influence of international air travel on the timing of influenza
      introduction, as well as an influence of domestic air travel on the rate of inter
      regional influenza spread in the US. Pandemic preparedness strategies should
      account for a possible benefit of airline travel restrictions on influenza
      spread.

PMID- 16968116
TI  - Eight Americas: investigating mortality disparities across races, counties, and
      race-counties in the United States.
AB  - BACKGROUND: The gap between the highest and lowest life expectancies for race
      county combinations in the United States is over 35 y. We divided the race-county
      combinations of the US population into eight distinct groups, referred to as the
      "eight Americas," to explore the causes of the disparities that can inform
      specific public health intervention policies and programs. METHODS AND FINDINGS:
      The eight Americas were defined based on race, location of the county of
      residence, population density, race-specific county-level per capita income, and
      cumulative homicide rate. Data sources for population and mortality figures were
      the Bureau of the Census and the National Center for Health Statistics. We
      estimated life expectancy, the risk of mortality from specific diseases, health
      insurance, and health-care utilization for the eight Americas. The life
      expectancy gap between the 3.4 million high-risk urban black males and the 5.6
      million Asian females was 20.7 y in 2001. Within the sexes, the life expectancy
      gap between the best-off and the worst-off groups was 15.4 y for males (Asians
      versus high-risk urban blacks) and 12.8 y for females (Asians versus low-income
      southern rural blacks). Mortality disparities among the eight Americas were
      largest for young (15-44 y) and middle-aged (45-59 y) adults, especially for men.
      The disparities were caused primarily by a number of chronic diseases and
      injuries with well-established risk factors. Between 1982 and 2001, the ordering
      of life expectancy among the eight Americas and the absolute difference between
      the advantaged and disadvantaged groups remained largely unchanged. Self-reported
      health plan coverage was lowest for western Native Americans and low-income
      southern rural blacks. Crude self-reported health-care utilization, however, was
      slightly higher for the more disadvantaged populations. CONCLUSIONS: Disparities
      in mortality across the eight Americas, each consisting of millions or tens of
      millions of Americans, are enormous by all international standards. The observed
      disparities in life expectancy cannot be explained by race, income, or basic
      health-care access and utilization alone. Because policies aimed at reducing
      fundamental socioeconomic inequalities are currently practically absent in the
      US, health disparities will have to be at least partly addressed through public
      health strategies that reduce risk factors for chronic diseases and injuries.

PMID- 16968117
TI  - Birth outcome in women with previously treated breast cancer--a population-based
      cohort study from Sweden.
AB  - BACKGROUND: Data on birth outcome and offspring health after the appearance of
      breast cancer are limited. The aim of this study was to assess the risk of
      adverse birth outcomes in women previously treated for invasive breast cancer
      compared with the general population of mothers. METHODS AND FINDINGS: Of all
      2,870,932 singleton births registered in the Swedish Medical Birth Registry
      during 1973-2002, 331 first births following breast cancer surgery--with a mean
      time to pregnancy of 37 mo (range 7-163)--were identified using linkage with the
      Swedish Cancer Registry. Logistic regression analysis was used. The estimates
      were adjusted for maternal age, parity, and year of delivery. Odds ratios (ORs)
      and 95% confidence intervals (CIs) were used to estimate infant health and
      mortality, delivery complications, the risk of preterm birth, and the rates of
      instrumental delivery and cesarean section. The large majority of births from
      women previously treated for breast cancer had no adverse events. However, births
      by women exposed to breast cancer were associated with an increased risk of
      delivery complications (OR 1.5, 95% CI 1.2-1.9), cesarean section (OR 1.3, 95% CI
      1.0-1.7), very preterm birth (<32 wk) (OR 3.2, 95% CI 1.7-6.0), and low birth
      weight (<1500 g) (OR 2.9, 95% CI 1.4-5.8). A tendency towards an increased risk
      of malformations among the infants was seen especially in the later time period
      (1988-2002) (OR 2.1, 95% CI 1.2-3.7). CONCLUSIONS: It is reassuring that births
      overall were without adverse events, but our findings indicate that pregnancies
      in previously treated breast cancer patients should possibly be regarded as
      higher risk pregnancies, with consequences for their surveillance and management.

PMID- 16968118
TI  - Does academic medicine matter?

PMID- 16968119
TI  - Patient outcomes with teaching versus nonteaching healthcare: a systematic
      review.
AB  - BACKGROUND: Extensive debate exists in the healthcare community over whether
      outcomes of medical care at teaching hospitals and other healthcare units are
      better or worse than those at the respective nonteaching ones. Thus, our goal was
      to systematically evaluate the evidence pertaining to this question. METHODS AND
      FINDINGS: We reviewed all studies that compared teaching versus nonteaching
      healthcare structures for mortality or any other patient outcome, regardless of
      health condition. Studies were retrieved from PubMed, contact with experts, and
      literature cross-referencing. Data were extracted on setting, patients, data
      sources, author affiliations, definition of compared groups, types of diagnoses
      considered, adjusting covariates, and estimates of effect for mortality and for
      each other outcome. Overall, 132 eligible studies were identified, including 93
      on mortality and 61 on other eligible outcomes (22 addressed both). Synthesis of
      the available adjusted estimates on mortality yielded a summary relative risk of
      0.96 (95% confidence interval [CI], 0.93-1.00) for teaching versus nonteaching
      healthcare structures and 1.04 (95% CI, 0.99-1.10) for minor teaching versus
      nonteaching ones. There was considerable heterogeneity between studies (I(2) =
      72% for the main analysis). Results were similar in studies using clinical and
      those using administrative databases. No differences were seen in the 14 studies
      fully adjusting for volume/experience, severity, and comorbidity (relative risk
      1.01). Smaller studies did not differ in their results from larger studies.
      Differences were seen for some diagnoses (e.g., significantly better survival for
      breast cancer and cerebrovascular accidents in teaching hospitals and
      significantly better survival from cholecystectomy in nonteaching hospitals), but
      these were small in magnitude. Other outcomes were diverse, but typically
      teaching healthcare structures did not do better than nonteaching ones.
      CONCLUSIONS: The available data are limited by their nonrandomized design, but
      overall they do not suggest that a healthcare facility's teaching status on its
      own markedly improves or worsens patient outcomes. Differences for specific
      diseases cannot be excluded, but are likely to be small.

PMID- 16968120
TI  - SARS: systematic review of treatment effects.
AB  - BACKGROUND: The SARS outbreak of 2002-2003 presented clinicians with a new, life
      threatening disease for which they had no experience in treating and no research
      on the effectiveness of treatment options. The World Health Organization (WHO)
      expert panel on SARS treatment requested a systematic review and comprehensive
      summary of treatments used for SARS-infected patients in order to guide future
      treatment and identify priorities for research. METHODS AND FINDINGS: In response
      to the WHO request we conducted a systematic review of the published literature
      on ribavirin, corticosteroids, lopinavir and ritonavir (LPV/r), type I interferon
      (IFN), intravenous immunoglobulin (IVIG), and SARS convalescent plasma from both
      in vitro studies and in SARS patients. We also searched for clinical trial
      evidence of treatment for acute respiratory distress syndrome. Sources of data
      were the literature databases MEDLINE, EMBASE, BIOSIS, and the Cochrane Central
      Register of Controlled Trials (CENTRAL) up to February 2005. Data from
      publications were extracted and evidence within studies was classified using
      predefined criteria. In total, 54 SARS treatment studies, 15 in vitro studies,
      and three acute respiratory distress syndrome studies met our inclusion criteria.
      Within in vitro studies, ribavirin, lopinavir, and type I IFN showed inhibition
      of SARS-CoV in tissue culture. In SARS-infected patient reports on ribavirin, 26
      studies were classified as inconclusive, and four showed possible harm. Seven
      studies of convalescent plasma or IVIG, three of IFN type I, and two of LPV/r
      were inconclusive. In 29 studies of steroid use, 25 were inconclusive and four
      were classified as causing possible harm. CONCLUSIONS: Despite an extensive
      literature reporting on SARS treatments, it was not possible to determine whether
      treatments benefited patients during the SARS outbreak. Some may have been
      harmful. Clinical trials should be designed to validate a standard protocol for
      dosage and timing, and to accrue data in real time during future outbreaks to
      monitor specific adverse effects and help inform treatment.

PMID- 16968122
TI  - Is DOTS-plus a feasible and cost-effective strategy?

PMID- 16968121
TI  - A new arthritis therapy with oxidative burst inducers.
AB  - BACKGROUND: Despite recent successes with biological agents as therapy for
      autoimmune inflammatory diseases such as rheumatoid arthritis (RA), many patients
      fail to respond adequately to these treatments, making a continued search for new
      therapies extremely important. Recently, the prevailing hypothesis that reactive
      oxygen species (ROS) promote inflammation was challenged when polymorphisms in
      Ncf1, that decrease oxidative burst, were shown to increase disease severity in
      mouse and rat arthritis models. Based on these findings we developed a new
      therapy for arthritis using oxidative burst-inducing substances. METHODS AND
      FINDINGS: Treatment of rats with phytol (3,7,11,15-tetramethyl-2-hexadecene-1-ol)
      increased oxidative burst in vivo and thereby corrected the effect of the genetic
      polymorphism in arthritis-prone Ncf1(DA) rats. Importantly, phytol treatment also
      decreased the autoimmune response and ameliorated both the acute and chronic
      phases of arthritis. When compared to standard therapies for RA, anti-tumour
      necrosis factor-alpha and methotrexate, phytol showed equally good or better
      therapeutic properties. Finally, phytol mediated its effect within hours of
      administration and involved modulation of T cell activation, as injection
      prevented adoptive transfer of disease with arthritogenic T cells. CONCLUSIONS:
      Treatment of arthritis with ROS-promoting substances such as phytol targets a
      newly discovered pathway leading to autoimmune inflammatory disease and
      introduces a novel class of therapeutics for treatment of RA and possibly other
      chronic inflammatory diseases.

PMID- 16968123
TI  - Feasibility and cost-effectiveness of treating multidrug-resistant tuberculosis:
      a cohort study in the Philippines.
AB  - BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is an important global
      health problem, and a control strategy known as DOTS-Plus has existed since 1999.
      However, evidence regarding the feasibility, effectiveness, cost, and cost
      effectiveness of DOTS-Plus is still limited. METHODOLOGY/PRINCIPAL FINDINGS: We
      evaluated the feasibility, effectiveness, cost, and cost-effectiveness of a DOTS
      Plus pilot project established at Makati Medical Center in Manila, the
      Philippines, in 1999. Patients with MDR-TB are treated with regimens, including
      first- and second-line drugs, tailored to their drug susceptibility pattern
      (i.e., individualised treatment). We considered the cohort enrolled between April
      1999 and March 2002. During this three-year period, 118 patients were enrolled in
      the project; 117 were considered in the analysis. Seventy-one patients (61%) were
      cured, 12 (10%) failed treatment, 18 (15%) died, and 16 (14%) defaulted. The
      average cost per patient treated was US3,355 dollars from the perspective of the
      health system, of which US1,557 dollars was for drugs, and US837 dollars from the
      perspective of patients. The mean cost per disability-adjusted life year (DALY)
      gained by the DOTS-Plus project was US242 dollars (range US85 dollars to US426
      dollars). CONCLUSIONS: Treatment of patients with MDR-TB using the DOTS-Plus
      strategy and individualised drug regimens can be feasible, comparatively
      effective, and cost-effective in low- and middle-income countries.

PMID- 16968125
TI  - Shigellosis: an old disease in new clothes?

PMID- 16968124
TI  - A multicentre study of Shigella diarrhoea in six Asian countries: disease burden,
      clinical manifestations, and microbiology.
AB  - BACKGROUND: The burden of shigellosis is greatest in resource-poor countries.
      Although this diarrheal disease has been thought to cause considerable morbidity
      and mortality in excess of 1,000,000 deaths globally per year, little recent data
      are available to guide intervention strategies in Asia. We conducted a
      prospective, population-based study in six Asian countries to gain a better
      understanding of the current disease burden, clinical manifestations, and
      microbiology of shigellosis in Asia. METHODS AND FINDINGS: Over 600,000 persons
      of all ages residing in Bangladesh, China, Pakistan, Indonesia, Vietnam, and
      Thailand were included in the surveillance. Shigella was isolated from 2,927 (5%)
      of 56,958 diarrhoea episodes detected between 2000 and 2004. The overall
      incidence of treated shigellosis was 2.1 episodes per 1,000 residents per year in
      all ages and 13.2/1,000/y in children under 60 months old. Shigellosis incidence
      increased after age 40 years. S. flexneri was the most frequently isolated
      Shigella species (1,976/2,927 [68%]) in all sites except in Thailand, where S.
      sonnei was most frequently detected (124/146 [85%]). S. flexneri serotypes were
      highly heterogeneous in their distribution from site to site, and even from year
      to year. PCR detected ipaH, the gene encoding invasion plasmid antigen H in 33%
      of a sample of culture-negative stool specimens. The majority of S. flexneri
      isolates in each site were resistant to amoxicillin and cotrimoxazole.
      Ciprofloxacin-resistant S. flexneri isolates were identified in China (18/305
      [6%]), Pakistan (8/242 [3%]), and Vietnam (5/282 [2%]). CONCLUSIONS: Shigella
      appears to be more ubiquitous in Asian impoverished populations than previously
      thought, and antibiotic-resistant strains of different species and serotypes have
      emerged. Focusing on prevention of shigellosis could exert an immediate benefit
      first by substantially reducing the overall diarrhoea burden in the region and
      second by preventing the spread of panresistant Shigella strains. The
      heterogeneous distribution of Shigella species and serotypes suggest that
      multivalent or cross-protective Shigella vaccines will be needed to prevent
      shigellosis in Asia.

PMID- 16968126
TI  - Geographic data on health inequities: understanding policy implications.

PMID- 16968127
TI  - Live, attenuated influenza A H5N1 candidate vaccines provide broad cross
      protection in mice and ferrets.
AB  - BACKGROUND: Recent outbreaks of highly pathogenic influenza A H5N1 viruses in
      humans and avian species that began in Asia and have spread to other continents
      underscore an urgent need to develop vaccines that would protect the human
      population in the event of a pandemic. METHODS AND FINDINGS: Live, attenuated
      candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA) and
      a wild-type (wt) N1 neuraminidase from influenza A H5N1 viruses isolated in Hong
      Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived
      from the cold-adapted (ca) influenza A vaccine donor strain, influenza A/Ann
      Arbor/6/60 ca (H2N2), were generated by reverse genetics. The H5N1 ca vaccine
      viruses required trypsin for efficient growth in vitro, as predicted by the
      modification engineered in the gene encoding the HA, and possessed the
      temperature-sensitive and attenuation phenotypes specified by the internal
      protein genes of the ca vaccine donor strain. More importantly, the candidate
      vaccines were immunogenic in mice. Four weeks after receiving a single dose of
      10(6) 50% tissue culture infectious doses of intranasally administered vaccines,
      mice were fully protected from lethality following challenge with homologous and
      antigenically distinct heterologous wt H5N1 viruses from different genetic
      sublineages (clades 1, 2, and 3) that were isolated in Asia between 1997 and
      2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were
      fully protected against pulmonary replication of homologous and heterologous wt
      H5N1 viruses. CONCLUSIONS: The promising findings in these preclinical studies of
      safety, immunogenicity, and efficacy of the H5N1 ca vaccines against
      antigenically diverse H5N1 vaccines provide support for their careful evaluation
      in Phase 1 clinical trials in humans.

PMID- 16968128
TI  - Antidepressants and violence: problems at the interface of medicine and law.

PMID- 16968129
TI  - A step closer to meeting the threat of avian influenza.

PMID- 16968130
TI  - Regenerative medicine and the developing world.

PMID- 16968131
TI  - Harmful waste products as novel immune modulators for treating inflammatory
      arthritis?

PMID- 16968132
TI  - Predicting essential components of signal transduction networks: a dynamic model
      of guard cell abscisic acid signaling.
AB  - Plants both lose water and take in carbon dioxide through microscopic stomatal
      pores, each of which is regulated by a surrounding pair of guard cells. During
      drought, the plant hormone abscisic acid (ABA) inhibits stomatal opening and
      promotes stomatal closure, thereby promoting water conservation. Dozens of
      cellular components have been identified to function in ABA regulation of guard
      cell volume and thus of stomatal aperture, but a dynamic description is still not
      available for this complex process. Here we synthesize experimental results into
      a consistent guard cell signal transduction network for ABA-induced stomatal
      closure, and develop a dynamic model of this process. Our model captures the
      regulation of more than 40 identified network components, and accords well with
      previous experimental results at both the pathway and whole-cell physiological
      level. By simulating gene disruptions and pharmacological interventions we find
      that the network is robust against a significant fraction of possible
      perturbations. Our analysis reveals the novel predictions that the disruption of
      membrane depolarizability, anion efflux, actin cytoskeleton reorganization,
      cytosolic pH increase, the phosphatidic acid pathway, or K(+) efflux through
      slowly activating K(+) channels at the plasma membrane lead to the strongest
      reduction in ABA responsiveness. Initial experimental analysis assessing ABA
      induced stomatal closure in the presence of cytosolic pH clamp imposed by the
      weak acid butyrate is consistent with model prediction. Simulations of stomatal
      response as derived from our model provide an efficient tool for the
      identification of candidate manipulations that have the best chance of conferring
      increased drought stress tolerance and for the prioritization of future wet bench
      analyses. Our method can be readily applied to other biological signaling
      networks to identify key regulatory components in systems where quantitative
      information is limited.

PMID- 16968133
TI  - Threshold-dependent BMP-mediated repression: a model for a conserved mechanism
      that patterns the neuroectoderm.
AB  - Subdivision of the neuroectoderm into three rows of cells along the dorsal
      ventral axis by neural identity genes is a highly conserved developmental
      process. While neural identity genes are expressed in remarkably similar patterns
      in vertebrates and invertebrates, previous work suggests that these patterns may
      be regulated by distinct upstream genetic pathways. Here we ask whether a
      potential conserved source of positional information provided by the BMP
      signaling contributes to patterning the neuroectoderm. We have addressed this
      question in two ways: First, we asked whether BMPs can act as bona fide
      morphogens to pattern the Drosophila neuroectoderm in a dose-dependent fashion,
      and second, we examined whether BMPs might act in a similar fashion in patterning
      the vertebrate neuroectoderm. In this study, we show that graded BMP signaling
      participates in organizing the neural axis in Drosophila by repressing expression
      of neural identity genes in a threshold-dependent fashion. We also provide
      evidence for a similar organizing activity of BMP signaling in chick neural plate
      explants, which may operate by the same double negative mechanism that acts
      earlier during neural induction. We propose that BMPs played an ancestral role in
      patterning the metazoan neuroectoderm by threshold-dependent repression of neural
      identity genes.

PMID- 16968134
TI  - Inhibition of gap junction communication at ectopic Eph/ephrin boundaries
      underlies craniofrontonasal syndrome.
AB  - Mutations in X-linked ephrin-B1 in humans cause craniofrontonasal syndrome
      (CFNS), a disease that affects female patients more severely than males. Sorting
      of ephrin-B1-positive and -negative cells following X-inactivation has been
      observed in ephrin-B1(+/-) mice; however, the mechanisms by which mosaic ephrin
      B1 expression leads to cell sorting and phenotypic defects remain unknown. Here
      we show that ephrin-B1(+/-) mice exhibit calvarial defects, a phenotype
      autonomous to neural crest cells that correlates with cell sorting. We have
      traced the causes of calvarial defects to impaired differentiation of osteogenic
      precursors. We show that gap junction communication (GJC) is inhibited at ectopic
      ephrin boundaries and that ephrin-B1 interacts with connexin43 and regulates its
      distribution. Moreover, we provide genetic evidence that GJC is implicated in the
      calvarial defects observed in ephrin-B1(+/-) embryos. Our results uncover a novel
      role for Eph/ephrins in regulating GJC in vivo and suggest that the pleiotropic
      defects seen in CFNS patients are due to improper regulation of GJC in affected
      tissues.

PMID- 16968135
TI  - Generalization of motor learning depends on the history of prior action.
AB  - Generalization of motor learning refers to our ability to apply what has been
      learned in one context to other contexts. When generalization is beneficial, it
      is termed transfer, and when it is detrimental, it is termed interference.
      Insight into the mechanism of generalization may be acquired from understanding
      why training transfers in some contexts but not others. However, identifying
      relevant contextual cues has proven surprisingly difficult, perhaps because the
      search has mainly been for cues that are explicit. We hypothesized instead that a
      relevant contextual cue is an implicit memory of action with a particular body
      part. To test this hypothesis we considered a task in which participants learned
      to control motion of a cursor under visuomotor rotation in two contexts: by
      moving their hand through motion of their shoulder and elbow, or through motion
      of their wrist. Use of these contextual cues led to three observations: First, in
      naive participants, learning in the wrist context was much faster than in the arm
      context. Second, generalization was asymmetric so that arm training benefited
      subsequent wrist training, but not vice versa. Third, in people who had prior
      wrist training, generalization from the arm to the wrist was blocked. That is,
      prior wrist training appeared to prevent both the interference and transfer that
      subsequent arm training should have caused. To explain the data, we posited that
      the learner collected statistics of contextual history: all upper arm movements
      also move the hand, but occasionally we move our hands without moving the upper
      arm. In a Bayesian framework, history of limb segment use strongly affects
      parameter uncertainty, which is a measure of the covariance of the contextual
      cues. This simple Bayesian prior dictated a generalization pattern that largely
      reproduced all three findings. For motor learning, generalization depends on
      context, which is determined by the statistics of how we have previously used the
      various parts of our limbs.

PMID- 16968136
TI  - Morphological evolution is accelerated among island mammals.
AB  - Dramatic evolutionary changes occur in species isolated on islands, but it is not
      known if the rate of evolution is accelerated on islands relative to the
      mainland. Based on an extensive review of the literature, I used the fossil
      record combined with data from living species to test the hypothesis of an
      accelerated morphological evolution among island mammals. I demonstrate that
      rates of morphological evolution are significantly greater--up to a factor of 3.1
      -for islands than for mainland mammal populations. The tendency for faster
      evolution on islands holds over relatively short time scales--from a few decades
      up to several thousands of years--but not over larger ones--up to 12 million y.
      These analyses form the first empirical test of the long held supposition of
      accelerated evolution among island mammals. Moreover, this result shows that
      mammal species have the intrinsic capacity to evolve faster when confronted with
      a rapid change in their environment. This finding is relevant to our
      understanding of species' responses to isolation and destruction of natural
      habitats within the current context of rapid climate warming.

PMID- 16968137
TI  - Initiation, establishment, and maintenance of heritable MuDR transposon silencing
      in maize are mediated by distinct factors.
AB  - Paramutation and transposon silencing are two epigenetic phenomena that have
      intrigued and puzzled geneticists for decades. Each involves heritable changes in
      gene activity without changes in DNA sequence. Here we report the cloning of a
      gene whose activity is required for the maintenance of both silenced transposons
      and paramutated color genes in maize. We show that this gene, Mop1 (Mediator of
      paramutation1) codes for a putative RNA-dependent RNA polymerase, whose activity
      is required for the production of small RNAs that correspond to the MuDR
      transposon sequence. We also demonstrate that although Mop1 is required to
      maintain MuDR methylation and silencing, it is not required for the initiation of
      heritable silencing. In contrast, we present evidence that a reduction in the
      transcript level of a maize homolog of the nucleosome assembly protein 1 histone
      chaperone can reduce the heritability of MuDR silencing. Together, these data
      suggest that the establishment and maintenance of MuDR silencing have distinct
      requirements.

PMID- 16968139
TI  - Fundamental questions in biology.

PMID- 16968138
TI  - Cooperation among microorganisms.

PMID- 16968140
TI  - Environmental influences on the behavioral phenotype of Angelman syndrome.
AB  - Using observational methods, we examined the social influences on laughing and
      smiling behavior in children with Angelman syndrome by systematically
      manipulating aspects of social interaction. Seven boys and 4 girls who were
      between 4 and 11 years of age and who had a confirmed maternal deletion of
      chromosome 15q11-q13 completed the study. Each child was observed while
      repeatedly exposed to three conditions in which parameters of social interaction
      were manipulated. Laughing and smiling behavior varied across all children and
      was significantly heightened in a condition involving adult speech, touch,
      smiling, laughing, and eye contact. The findings highlight the importance of
      examining environmental and social influences on purported phenotypic behavior in
      genetic syndromes.

PMID- 16968141
TI  - Large state-level fluctuations in mental retardation classifications related to
      introduction of renormed intelligence test.
AB  - Oppositely valenced forces may be at work to influence rates of placement of
      children into mental retardation programs. On one hand, educational policies
      regarding intellectual disability and concerns about overrepresentation of
      minorities in special education may contribute to lower placement rates; on the
      other hand, more difficult intelligence test norms may be a countervailing force,
      increasing placement rates. An analysis of longitudinal data on state and
      national level placement rates reveals that a lengthy and steep 12-year decline
      in students receiving mental retardation services reversed shortly after the
      introduction of the WISC-III in 1991. This phenomenon has relevance for death
      penalty cases, because this historical pattern may affect the ability to
      establish whether an adult meets the developmental period onset criterion for
      mental retardation.

PMID- 16968142
TI  - Promoting the peer-related social development of young children with mild
      developmental delays: effectiveness of a comprehensive intervention.
AB  - To address the unusual peer-related social competence difficulties characteristic
      of young children with mild developmental delays, we conducted a randomized
      clinical trial to evaluate the effectiveness of a comprehensive, developmentally
      oriented, highly individualized intervention extending over a 2-year period.
      Outcome measures emphasized generalization of peer interactions in unfamiliar
      playgroups. Results revealed modest effects of the intervention, with children
      who had lower cognitive levels benefiting most. Intervention effects were best
      conceptualized as preventative, minimizing the negative features and atypical
      patterns of children's social play with peers. Our discussion of future work was
      focused on alternative implementation models to enhance intervention intensity,
      inclusion of specific subgroups of children, and direct measurement of children
      engaging in social tasks.

PMID- 16968144
TI  - Teaching sight words to children with moderate to mild mental retardation:
      comparison between instructional procedures.
AB  - Differential effects of three training procedures to teach sight words to 13
      children with moderate to mild mental retardation were investigated in an
      alternating treatments design. Number of correct responses was assessed during
      probe sessions in word-alone (word was presented without picture), integrated
      picture (word was presented with integrated picture, no fading), and picture
      fading (integrated picture was faded out) conditions. Results show that most
      children learned to identify sight words fastest in the word-alone condition.
      Effects were largely maintained during follow-up at 2 to 5 weeks after training.

PMID- 16968145
TI  - Relationships between facial discrimination and social adjustment in mental
      retardation.
AB  - Sixty-two adults with mental retardation of heterogeneous etiology performed four
      facial emotion discrimination tasks and two facial nonemotion tasks. Staff
      members familiar with the participants completed measures of social adjustment
      (the Socialization and Communication domains of the Vineland Adaptive Behavior
      Scales and the Social Performance Survey Schedule). All facial discrimination
      tasks had very good reliability (internal consistency), but only some of the
      tasks correlated with measures of social adjustment. Furthermore, no evidence was
      found that emotion tasks and nonemotion tasks assessed different social
      constructs. Emotion tasks in which participants were presented with visual
      emotion stimuli correlated significantly with prosocial behavior, whereas those
      with verbal emotion stimuli did not.

PMID- 16968146
TI  - Mania and intellectual disability: the course of manic symptoms in persons with
      intellectual disability.
AB  - Our aim was to extend the literature by examining the presence of manic symptoms
      in persons with intellectual deficits with and without bipolar disorder for 3
      years. Three groups (bipolar, psychopathology other than bipolar disorder, and no
      Axis I diagnosis) were formed with 14 participants in each group. Initially, the
      presence of mania symptoms were examined across diagnostic groups. The bipolar
      group had significantly greater endorsements on the Parent Version of the Young
      Mania Rating Scale and the DASH-II Mania subscale item "decreased need for sleep"
      than did the other groups. A 3 (group) x 3 (year) ANOVA revealed that the item
      endorsements differed significantly over time for the bipolar group but not the
      other groups. Implications of these findings are discussed.

PMID- 16968147
TI  - Trends in tissue engineering research.
AB  - For more than a decade, Tissue Engineering has been devoted to the reporting and
      discussion of scientific advances in the interdisciplinary field of tissue
      engineering. In this study, 779 original articles published in the journal since
      its inception were analyzed and classified according to different attributes,
      such as focus of research and tissue of interest, to reveal trends in tissue
      engineering research. In addition, the use of different biomaterials, scaffold
      architectures, surface and bulk modification agents, cells, differentiation
      factors, gene delivery vectors, and animal models was examined. The results of
      this survey show interesting trends over time and by continental origin.

PMID- 16968148
TI  - Decellularized xenogenic heart valves reveal remodeling and growth potential in
      vivo.
AB  - We have developed an advanced tissue processing technique on porcine pulmonary
      heart valves for pulmonary valve replacement and its initial clinical application
      during the autograft operation according to Ross. The novel concept consists of a
      cell-free matrix achieved by deoxycholic acid treatment that is repopulated by
      host cells in vivo. Molecular biology, radioligand binding, and electron
      microscopy consistently showed that these valves are almost free of cellular
      components. Animal experiments and clinical investigations revealed excellent
      hemodynamic properties of the valves, no need for antithrombotic therapy, and
      repopulation by host cells without any signs of calcification. In juvenile sheep
      the internal diameter of the implanted valves significantly increased in growing
      animals by approximately 10 mm. The repopulation of the decellularized heart
      valves was found not only in sheep but also in humans, which indicates that the
      underlying mechanisms, presumably repair mechanisms, might be common in mammals.
      If these findings can be confirmed by others, they will lead to new concepts in
      the field of cardiovascular tissue engineering that will eliminate the need for
      in vitro construction of autologous heart valves.

PMID- 16968149
TI  - Tissue engineering of tooth crown, root, and periodontium.
AB  - Tissue engineering of teeth requires the coordinated formation of correctly
      shaped crowns, roots, and periodontal ligament. Previous studies have shown that
      the dental mesenchyme controls crown morphogenesis and epithelial histogenesis
      during tooth development in vivo, but little is known about the inductive
      potential of dissociated mesenchymal cells used in ex vivo cultures. A 2-step
      method is described in which, by using different types of reassociations between
      epithelial and mesenchymal tissues and/or cells from mouse embryos,
      reassociations were cultured in vitro before in vivo implantation. In vitro, the
      reassociated tissues developed and resulted in tooth-like structures that
      exhibited normal epithelial histogenesis and allowed the functional
      differentiation of odontoblasts and ameloblasts. After implantation, the
      reassociations formed roots and periodontal ligament, the latter connected to
      developing bone. The shape of the crown, initially suspected to depend on the
      integrity of the mesenchyme, could be modulated by adjusting the number of
      dissociated mesenchymal cells reassociated with the epithelial compartment. Based
      on these results, we propose a refined strategy for tooth tissue engineering that
      may help to eventually generate morphologically defined teeth.

PMID- 16968150
TI  - Biomimetic approach to cardiac tissue engineering: oxygen carriers and channeled
      scaffolds.
AB  - We report that the functional assembly of engineered cardiac muscle can be
      enhanced by oxygen supply provided by mechanisms resembling those in normal
      vascularized tissues. To mimic the capillary network, cardiomyocytes and
      fibroblasts isolated from the neonatal rat hearts were cultured on a highly
      porous elastomer with a parallel array of channels that were perfused with
      culture medium. To mimic oxygen supply by hemoglobin, culture medium was
      supplemented with a perfluorocarbon (PFC) emulsion; constructs perfused with
      unsupplemented culture medium served as controls. In PFC-supplemented medium, the
      decrease in the partial pressure of oxygen in the aqueous phase was only 50% of
      that in control medium (28 mmHg vs. 45 mmHg between the construct inlet and
      outlet at a flow rate of 0.1 mL/min). Consistently, constructs cultivated in the
      presence of PFC contained higher amounts of DNA and cardiac markers (troponin I,
      connexin-43) and had significantly better contractile properties as compared to
      control constructs. In both groups, electron microscopy revealed open channels
      and the presence of cells at the channel surfaces as well as within constructs.
      Improved properties of cardiac constructs could be correlated with the enhanced
      supply of oxygen to the cells, by a combined use of channeled scaffolds and PFC.

PMID- 16968151
TI  - Angiogenesis in tissue engineering: breathing life into constructed tissue
      substitutes.
AB  - Long-term function of three-dimensional (3D) tissue constructs depends on
      adequate vascularization after implantation. Accordingly, research in tissue
      engineering has focused on the analysis of angiogenesis. For this purpose, 2
      sophisticated in vivo models (the chorioallantoic membrane and the dorsal
      skinfold chamber) have recently been introduced in tissue engineering research,
      allowing a more detailed analysis of angiogenic dysfunction and engraftment
      failure. To achieve vascularization of tissue constructs, several approaches are
      currently under investigation. These include the modification of biomaterial
      properties of scaffolds and the stimulation of blood vessel development and
      maturation by different growth factors using slow-release devices through pre
      encapsulated microspheres. Moreover, new microvascular networks in tissue
      substitutes can be engineered by using endothelial cells and stem cells or by
      creating arteriovenous shunt loops. Nonetheless, the currently used techniques
      are not sufficient to induce the rapid vascularization necessary for an adequate
      cellular oxygen supply. Thus, future directions of research should focus on the
      creation of microvascular networks within 3D tissue constructs in vitro before
      implantation or by co-stimulation of angiogenesis and parenchymal cell
      proliferation to engineer the vascularized tissue substitute in situ.

PMID- 16968152
TI  - Glucagon-like peptide-1 differentiation of primate embryonic stem cells into
      insulin-producing cells.
AB  - The present study was performed to determine whether glucagon-like peptide-1 (GLP
      1) stimulates differentiation of nestin-selected embryonic stem cells into
      insulin-producing cells. Our experimental strategy began with the production of a
      highly enriched population of nestin-positive cells from embryoid bodies. These
      cells differentiated into insulin-producing cells after addition of GLP-1. Islet
      like cell clusters (ICCs) formed in inducing culture. These nestin-positive cell
      derived ICCs expressed numerous beta-cell lineage genes, including insulin; Glut
      2; pancreatic duodenal homebox-1 protein (PDX-1); islet amyloid polypeptide
      (IAPP); neurogenin 3 (ngn3); and alpha, gamma, and delta cell gene markers. Cells
      of ICCs showed increased insulin protein expression, glucose-dependent insulin
      release, and coexpression of insulin and C-peptide. In addition, ICCs were
      characterized by coexpression of nestin/insulin and nestin/PDX-1. The levels of
      pancreas-related gene and protein expression and insulin secretion in the GLP-1
      group were stronger than those in the normal controls. GLP-1 has been shown to be
      involved in stimulating the signaling pathways downstream of the transcription
      factor PDX-1, by increasing its protein and messenger RNA levels. In vivo, ICCs
      displayed the ability to reverse hyperglycemia in diabetic severe combined
      immunodeficiency (SCID) mice. We concluded that GLP-1 induced differentiation of
      nestin-positive progenitor embryonic stem cells into insulin-producing cells,
      which was achieved by upregulation of PDX-1 expression. This method may have
      future applications in stem cell therapy of diabetes.

PMID- 16968153
TI  - Production of an acellular amniotic membrane matrix for use in tissue
      engineering.
AB  - A clinical need exists for an immunologically compatible surgical patch with a
      wide range of uses including soft tissue replacement, body wall repair,
      cardiovascular applications, and as a wound dressing. This study aimed to produce
      an acellular matrix from human amniotic membrane for future assessment as a
      surgical patch and a delivery system for epithelial cells. A novel detergent
      based protocol was modified to remove all cellular components from amnion to
      render it non-immunogenic. Amnion was harvested within 24 h after elective
      caesarean section (n = 12). One sample group remained fresh, whereas the other
      was treated with 0.03% (w/v) sodium dodecyl sulphate, with hypotonic buffer and
      protease inhibitors, nuclease treatment, and terminal sterilization, using
      peracetic acid (0.1% v/v). Fresh and treated amnion was analyzed histologically
      for the presence of cells, deoxyribonucleic acid (DNA), collagen,
      glycosaminoglycans (GAGs), and elastin. Quantitative analysis was performed to
      determine levels of GAGs, elastin, hydroxyproline, denatured collagen, and DNA.
      The biomechanical properties of the membrane were determined using uniaxial
      tensile testing to failure. Histological analysis of treated human amnion showed
      complete removal of cellular components from the tissue; the histoarchitecture
      remained intact. All major structural components of the matrix were retained,
      including collagen type IV and I, laminin, and fibronectin. Differences were
      observed between fresh and decellularized amnion in matrix hydroxyproline (34.7
      microg/mg vs 49.7 microg/mg), GAG (42.5 microg/mg vs 85.4 microg/mg), denatured
      collagen (2.2 microg/mg vs 1.7 microg/mg), and elastin (359.2 microg/mg vs 490.8
      microg/mg) content. DNA content was diminished after treatment. Acellular
      matrices were biocompatible, cells grew in contact, and there was no decrease in
      cell viability after incubation with soluble tissue extracts. In addition, no
      significant reduction in ultimate tensile strength, extensibility, or elasticity
      was found after decellularization. Removal of the cellular components should
      eliminate immunological rejection. The resulting matrix was biocompatible in
      vitro and exhibited no adverse effects on cell morphology or viability.

PMID- 16968154
TI  - Review. Hyaluronan: a powerful tissue engineering tool.
AB  - Hyaluronan (HA) is a versatile molecular tool with considerable potential for
      tissue engineering applications. The inclusion of HA has created biocompatible
      biomaterials and engineered tissues that can be crosslinked or degraded
      controllably and can facilitate angiogenesis, osteointegration, and cell
      phenotype preservation. The utility of HA in tissue engineering has been
      broadened further by the recently identified HA synthases, which can be
      manipulated to stimulate the endogenous production of HA by cells seeded within
      biomaterial scaffolds. Overall, HA shows great promise in the development of
      engineered tissues and biomaterials for a variety of biomedical needs including
      orthopedic, cardiovascular, pharmacologic, and oncologic applications.

PMID- 16968155
TI  - Visual histological grading system for the evaluation of in vitro-generated
      neocartilage.
AB  - Here we present the development of a visual evaluation system for routine
      assessment of in vitro-engineered cartilaginous tissue. Neocartilage was produced
      by culturing human articular chondrocytes in pellet culture systems or in a
      scaffold-free bioreactor system. All engineered tissues were embedded in paraffin
      and were sectioned and stained with Safranin O-fast green. The evaluation of each
      sample was broken into 3 categories (uniformity and intensity of Safranin O
      stain, distance between cells/amount of matrix produced, and cell morphology),
      and each category had 4 components with a score ranging from 0 to 3. Three
      observers evaluated each sample, and the new system was independently tested
      against an objective computer-based histomorphometry system. Pellets were also
      assessed biochemically for glycosaminoglycan (GAG) content. Pellet histology
      scores correlated significantly with GAG contents and were in agreement with the
      computer-based histomorphometry system. This system allows a valid and rapid
      assessment of in vitro-generated cartilaginous tissue that has a relevant
      association with objective parameters indicative of cartilage quality.

PMID- 16968156
TI  - Design of custom-shaped vascularized tissues using microtissue spheroids as
      minimal building units.
AB  - Tissue engineering strategies are gathering clinical momentum in regenerative
      medicine and are expected to provide excellent opportunities for therapy for
      difficult-to-treat human pathologies. Being aware of the requirement to produce
      larger artificial tissue implants for clinical applications, we used
      microtissues, produced using gravity-enforced self-assembly of monodispersed
      primary cells, as minimal tissue units to generate scaffold-free vascularized
      artificial macrotissues in custom-shaped agarose molds. Mouse myoblast, pig and
      human articular-derived chondrocytes, and human myofibroblast (HMF)-composed
      microtissues (microm3 scale) were amalgamated to form coherent macrotissue
      patches (mm3 scale) of a desired shape. Macrotissues, assembled from the human
      umbilical vein endothelial cell (HUVEC)-coated HMF microtissues, developed a
      vascular system, which functionally connected to the chicken embryo's vasculature
      after implantation. The design of scaffold-free vascularized macrotissues is a
      first step toward the scale-up and production of artificial tissue implants for
      future tissue engineering initiatives.

PMID- 16968157
TI  - Co-culture of umbilical cord blood CD34+ cells with human mesenchymal stem cells.
AB  - Insufficient numbers of hematopoietic stem cells (HSCs) and hematopoietic
      progenitor cells (HPCs) sometimes limit allogenic transplantation of umbilical
      cord blood (UCB). Ex vivo expansion may overcome this limitation. Mesenchymal
      stem cells (MSCs), as non-hematopoietic, well-characterized skeletal and
      connective-tissue progenitor cells within the bone marrow stroma, have been
      investigated as support cells for the culture of HSCs/HPCs. MSCs are attractive
      for the rich environmental signals that they provide and for immunological
      compatibility in transplantation. Thus far, HSC/MSC co-cultures have mainly been
      performed in 2-dimensional (2D) configuration. We postulate that a 3-dimensional
      (3D) culture environment that resembles the natural in vivo hematopoietic
      compartment might be more conducive for regulating HSC expansion. In this study,
      we compared the co-culture of HSCs and MSCs in 2D and 3D configurations. The
      results demonstrated the benefit of MSC inclusion in HSC expansion ex vivo.
      Direct contact between MSCs and HSCs in 3D cultures led to statistically
      significantly higher expansion of cord blood CD34+ cells than in 2D cultures (891
      versus 545-fold increase in total cells, 96- versus 48-fold increase of CD34+
      cells, and 230- versus 150-fold increase in colony-forming cell assay [CFC]).
      Engraftment assays in non-obese diabetic/severe combined immunodeficiency mice
      also indicated a high success rate of hematopoiesis reconstruction with these
      expanded cells.

PMID- 16968158
TI  - Vocal fold tissue repair in vivo using a synthetic extracellular matrix.
AB  - Chemically modified hyaluronic acid (HA)-gelatin hydrogels have been documented
      to support attachment, growth, and proliferation of fibroblasts in vitro and to
      facilitate repair and engineering of tissues in vivo. The objective of this study
      was to determine the optimal composition of a synthetic extracellular matrix
      (sECM) that would promote wound repair and induce tissue regeneration in a rabbit
      vocal fold wound healing model. The sECM was formed using a thiol-modified
      semisynthetic glycosaminoglycan (GAG) derived of HA (Carbylan-SX) mixed with a
      thiolated gelatin derivative, co-cross-linked with poly(ethylene glycol)
      diacrylate to form Carbylan-GSX. Forty rabbits underwent vocal fold biopsy
      bilaterally. Rabbits were treated with Carbylan-SX, which lacks gelatin, or with
      Carbylan-GSX with different gelatin concentrations (2.5%, 5%, 10%, and 20%) via
      unilateral injection of the vocal fold at the time of biopsy. Saline was injected
      in the contralateral vocal fold as a control. Three weeks after biopsy and
      injection, animals were euthanized and mRNA levels of procollagen type 1,
      fibronectin, transforming growth factor beta 1 (TGF-beta1), fibromodulin, HA
      synthase 2, hyaluronidase 2, and tissue biomechanics were evaluated.
      Hyaluronidase mRNA levels were found to be significantly elevated in for Carbylan
      GSX 20% w/w gelatin compared to controls. Both Carbylan-SX and Carbylan-GSX
      significantly improved tissue elasticity and viscosity. Carbylan-GSX containing
      5% w/w gelatin showed the most promise as a scaffold material for vocal fold
      tissue regeneration.

PMID- 16968159
TI  - Improved hepatocyte excretory function by immediate presentation of polarity
      cues.
AB  - Liver tissue constructs with excretory function are crucial to developing
      realistic hepatocyte models for engineering effective bioartificial liver
      assisted devices and for modeling the in vivo tissue. Current hepatocyte in vitro
      models suffer from limited or inefficient hepatocyte repolarization, which
      results in poor removal of xenobiotics and other waste products from the cells.
      We hypothesized that the temporal and spatial presentation of the cell matrix and
      cell-cell contacts as polarity cues would be important to define the axis of
      polarization to improve the excretory function of hepatocytes. The spatial
      presentation of polarity cues can be best achieved with sandwich configuration.
      We improve the temporal presentation of polarity cues by introducing the collagen
      overlay immediately in synchrony with cell-cell contacts instead of after 24 h in
      conventional sandwich culture. We demonstrate that the immediate presentation of
      the collagen matrix overlay enhances the formation of apicobasolateral domains,
      tight junctions, and the recovery of the functional activity of 2 canalicular
      transporters, the multidrug resistance-associated protein (Mrp2) and P
      glycoprotein (P-gp) at 48 h of culture, and enhances the albumin secretion, urea
      production, and 7-ethoxyresorufin-O-deethylation cytochrome P450 activities of
      hepatocytes over 14 days of culture as compared to the 24-h overlay controls. The
      improvement in the excretory function of hepatocytes for the removal of waste
      products deleterious to cells may improve the functional maintenance and the in
      vivo fidelity of tissue-engineered liver constructs.

PMID- 16968160
TI  - Time and space evolution of transport properties in agarose-chondrocyte
      constructs.
AB  - During the development of de novo synthesized cartilage tissue engineered
      constructs, transport and biophysical properties are expected to change in time
      and space. Monitoring and control of the evolution of these parameters are of
      crucial importance to process biohybrid constructs in vitro. The aim of this work
      was to measure fluid and macromolecular transport and evolution of mechanical
      properties of tissue-engineered cartilage constructs as a function of culture
      time and extracellular matrix (ECM) production. It was found, in agreement with
      other literature reports, that mechanical and fluid transport properties of the
      constructs correlated well with time of culture and glycosaminoglycan (GAG)
      content. Further, diffusion coefficients of 2 probes, dextran (500 kDa) and
      bovine serum albumin (BSA), correlated well with GAG production. Diffusion
      coefficients (D) were measured with high spatial and temporal resolution by
      fluorescent recovery after photobleaching (FRAP). Diffusivity steadily decreases
      with time while it does not vary through the thickness of the specimen. On the
      basis of these results, an empirical relationship between diffusion coefficient
      and GAG content was proposed for the 2 probes analyzed. The results of this study
      provide useful information to optimize and control the tissue culture process in
      vitro.

PMID- 16968161
TI  - Species specificity of ectopic bone formation using periosteum-derived
      mesenchymal progenitor cells.
AB  - To investigate novel cell-based bone-engineering approaches using rabbit as a
      preclinical animal model, we compared the osteogenic potential of rabbit
      periosteum-derived cells (RPDCs) and human periosteum-derived cells (HPDCs) in
      vitro and in vivo. Adherent periosteal cells from both species were expanded in
      vitro and subsequently treated with osteogenic medium or bone morphogenetic
      protein 6 (BMP6). Alkaline phosphatase (ALP) activity was measured, and alizarin
      red staining was performed to evaluate osteogenic differentiation. In vivo
      ectopic bone formation was assessed by seeding 5x10(6) periosteal cells, grown in
      osteogenic conditions, in a Collagraft carrier and subsequent implantation
      subcutaneously in athymic mice. In vitro, growth analysis indicated that RPDCs
      expanded faster and were smaller than HPDCs under the same culture conditions.
      Osteogenic medium did not affect the ALP activity of HPDCs or RPDCs. In contrast,
      BMP6 stimulated ALP activity in cultured RPDCs and HPDCs but at different rates.
      In vivo, HPDCs gave rise to extensive bone formation, whereas RPDCs failed to
      make bone. In vivo, cell tracking revealed that engraftment and survival of HPDCs
      and RPDCs after 8 weeks in the implant were limited. Some HPDCs were incorporated
      into the newly formed bone. RPDCs and HPDCs displayed distinct growth
      characteristics and osteogenic differentiation capacity in vitro and in vivo
      under the culture conditions used. Our data indicate potential limitations of use
      of the rabbit as a preclinical model for cell-based treatments for bone repair.

PMID- 16968162
TI  - Osteogenic differentiation of mouse embryonic stem cells and mouse embryonic
      fibroblasts in a three-dimensional self-assembling peptide scaffold.
AB  - In the present work, we studied the differentiation capacity of mouse embryonic
      stem cells (mESCs) and mouse embryonic fibroblasts (MEFs) to differentiate into
      osteoblast-like cells in a 3-dimensional (3D) self-assembling peptide scaffold, a
      synthetic nanofiber biomaterial with potential applications in regenerative
      medicine. We demonstrated that 2D and 3D systems promoted differentiation of
      mESCs into cells with an osteoblast-like phenotype consisting of osteopontin and
      collagen I marker expression, as well as high alkaline phosphatase (ALP) activity
      and calcium phosphate deposits. In 3D cultures the frequency of appearance of
      embryonic stem cell-like colonies was substantially greater, suggesting that the
      3D microenvironment promoted the generation of a stem cell-like niche that allows
      undifferentiated stem cell maintenance. On the other hand, after MEFs were
      cultured in the 3D system with their regular growth medium, but not in the 2D
      system, they expressed osteopontin, up-regulated metalloproteinase activities,
      and acquired a distinct phenotype consisting of small, elongated cells with
      remaining mitotic activity. Furthermore, only 3D MEF cultures underwent
      osteoblast differentiation after osteogenic induction, based on matrix
      mineralization, collagen I synthesis, ALP activity, and expression of the
      osteoblast transcription factor Runx2, suggesting that the 3D environment
      promotes differentiation of MEFs into osteoblast-like cells. We propose that the
      3D system provides a unique microenvironment that promotes differentiation of
      mESCs and MEFs into osteoblast-like cells.

PMID- 16968163
TI  - Three-dimensional microchannels in biodegradable polymeric films for control
      orientation and phenotype of vascular smooth muscle cells.
AB  - The poor mechanical strength and vasoactivity of current small-diameter tissue
      engineered blood vessels (TEBVs) remain unsolved problems. Given the plasticity
      of smooth muscle cells (SMCs), 1 of the main limitations of current scaffolding
      techniques is the difficulty in controlling SMC phenotype shifts in vitro. A
      synthetic phenotype allows the cells to rapidly proliferate and produce
      extracellular matrix (ECM), whereas a shift to contractile phenotype with
      organized ECM ultimately provides a functional blood vessel. In this study, 3D
      deep (65 microm) and wide microchannels separated by high-aspect ratio (8)
      microwalls were successfully ultraviolet (UV) microembossed using a liquid UV
      polymerizable biodegradable macromer (poly(epsilon-caprolactone-r-L-lactide-r
      glycolide) diacrylate) and the in vitro guidance effects of varying channel width
      (40-160 microm) on SMCs were verified. The results show that SMCs cultured in the
      wider microchannels (80-160 microm wide) switch from fibroblast morphology and
      random orientation to spindle-shaped morphology, and align along the direction of
      the microchannel nearing confluence achieved with similar cell density to
      unpatterned film. Further, an enhanced expression of smooth muscle alpha-actin of
      SMCs grown on micropatterns was found nearing confluence, which demonstrates a
      phenotype shift to a more contractile phenotype. These films are flexible and can
      be folded into tubular and lamellar structures for tissue engineering of small
      diameter TEBVs as well as other organs such as esophagus or intestine. These
      results suggest that these micropatterned synthetic biodegradable scaffolds may
      be useful for guiding SMCs to grow into functional, small-diameter vascular
      grafts.

PMID- 16968164
TI  - Contribution of non-parenchymal cells to the performance of micropatterned
      hepatocytes.
AB  - Hepatocytes within current bioartificial liver designs are unable to maintain the
      wide range of differentiated functions observed for the liver in vivo. As recent
      studies suggest, the absence of controlled interactions between hepatocytes and
      non-parenchymal cell populations of the liver may contribute to this hepatocyte
      dedifferentiation. The current study investigates the effect of Kupffer cells,
      fibroblasts, and human umbilical vein endothelial cells on hepatocyte function.
      To effectively study the effect of these heterotypic cell-to-cell interactions,
      it is necessary to establish a culture environment that controls the interactions
      between multiple cell types. Micropatterning is such a technique and was used in
      the current study. In addition, to elucidate the influence of soluble factors on
      hepatocyte function, the micropatterned results were compared with those of the
      trans-well culture system. Specifically, we compared the morphological and
      functional changes of hepatocytes cultured with these cells at varying ratios.
      Our results suggest that direct heterotypic cell-to-cell contact between
      hepatocytes and fibroblasts, and soluble factor exchanges between hepatocytes and
      human umbilical vein endothelial cells, significantly enhanced hepatocyte
      performance.

PMID- 16968165
TI  - Dose- and time-dependent effects of cyclic hydrostatic pressure on transforming
      growth factor-beta3-induced chondrogenesis by adult human mesenchymal stem cells
      in vitro.
AB  - This study examined effects of varying magnitudes of intermittent hydrostatic
      pressure (IHP) applied for different times on chondrogenesis of adult human
      mesenchymal stem cells (hMSCs) in vitro. hMSCs were exposed to 0.1, 1, and 10 MPa
      of IHP at a frequency of 1 Hz for 4 h/day for 3, 7, and 14 days in the presence
      of transforming growth factor (TGF-beta3). Chondrogenesis was characterized by
      gene expression, macromolecule production, and extracellular matrix deposition.
      Exposure of hMSCs to 0.1 MPa of IHP increased SOX9 and aggrecan mRNA expression
      by 2.2- and 5.6-fold, respectively, whereas type II collagen mRNA expression
      responded maximally at 10 MPa. Production of sulfated glycosaminoglycan responded
      to IHP of 1 MPa and 10 MPa, whereas collagen levels increased only at 10 MPa.
      Morphologically, matrix condensation occurred with increased IHP, concomitant
      with collagen expression. This study demonstrated that different levels of IHP
      differentially modulate hMSC chondrogenesis in the presence of TGF-beta3. The
      data suggest that tissue engineering of articular cartilage through application
      or recruitment of hMSCs can be facilitated by mechanical stimulation.

PMID- 16968166
TI  - Human mesenchymal stem cells induce T cell anergy and downregulate T cell allo
      responses via the TH2 pathway: relevance to tissue engineering human heart
      valves.
AB  - To generate an ''off the shelf'' tissue-engineered heart valve, the cells would
      need to be of allogeneic origin. Here, we report the possibility of using human
      bone marrow-derived mesenchymal stem cells (MSCs) as a suitable allogeneic cell
      source for tissue-engineered heart valves. Proliferative responses of primary and
      primed CD4+ T cells to allogeneic MSCs were examined. A protein microarray system
      was used to detect soluble factors from supernatants collected from the T cell
      assays. MSCs are poor stimulators of primary and primed CD4+ T cell
      proliferation, despite provision of B7-1 trans-co-stimulation. MSCs not only
      directly inhibited primary and primed T cell responses to allogeneic peripheral
      blood mononuclear cells (PBMCs), but 24-h pre-culture of T cells with MSCs
      suppressed subsequent T cell proliferative responses to allogeneic PBMCs in a
      contact-dependent manner. Analysis of supernatants revealed a distinctly
      different cytokine profile after co-culture of T cells with MSCs than with PBMCs
      or endothelial cells. Pro-inflammatory Th1 cytokines interleukin (IL)-1alpha and
      beta, interferon (IFN)gamma, and tumor necrosis factor (TNF)alpha were
      downregulated, whereas, anti-inflammatory Th2 cytokines IL-3, IL-5, IL-10, and IL
      13 and the Th2 chemokine I-309, a chemoattractant for regulatory T cells, were
      upregulated. Further analysis revealed that after co-culture with MSCs, the T
      cells exhibited a regulatory phenotype (CD4+ CD25(lo) CD69(lo) FoxP3+). MSCs
      downregulate T cell responses through direct contact and secretion of anti
      inflammatory and tolerogenic cytokines, which may involve the recruitment of
      regulatory T cells. This implies that allogeneic MSCs could be a suitable cell
      source for tissue engineering a heart valve.

PMID- 16968167
TI  - Tissue-engineered human vascular media produced in vitro by the self-assembly
      approach present functional properties similar to those of their native blood
      vessels.
AB  - We have developed a tissue-engineering approach for the production of a
      completely biological blood vessel from cultured human cells. In the present
      study, we took advantage of this tissue-engineering method to demonstrate that it
      can be used to reproduce the subtle differences in the expression of receptors
      present on the media of native human blood vessels. Indeed, a small percentage (3
      of 18) of native human umbilical cord veins (HUCVs) responded to endothelin, the
      most powerful vasopressor agent known to date, via both endothelin A (ET(A)) and
      endothelin B (ET(B)) receptor activation. In contrast, most HUCVs tested
      responded to ET via ET(A) receptor activation only. Tissue-engineered vascular
      media (TEVM) were next reconstructed by using vascular smooth muscle cells
      (VSMCs) isolated and cultured from HUCVs expressing both ET(A) and ET(B)
      receptors to determine the functional integrity of our TEVM model. The
      reconstructed TEVM presents an endothelin response similar to that of respective
      HUCVs from which VSMCs were isolated. Reverse transcriptase polymerase chain
      reaction on TEVM reconstructed in vitro correlated these vasocontractile profiles
      by showing the presence of messenger RNA for both ET(A) and ET(B) receptors.
      Taken together with recently published results on TEVM expressing only ET(A)
      receptor, these results show that our reconstructed TEVM present a similar ET
      response profile as the blood vessel from which the VSMCs were isolated and
      cultured. These findings indicate that subtle differences, such as receptor
      expression, are preserved in the reconstructed tissue. Therefore, our TEVM offers
      a valuable human in vitro model with which to study the functionality of human
      blood vessels, such as their vasoactive response, or to perform pharmacologic
      studies.

PMID- 16968168
TI  - Biphasic calcium phosphate: a scaffold for growth plate chondrocyte maturation.
AB  - While skeletal development can occur by either intramembranous or endochondral
      bone formation, all current tissue engineering approaches for bone repair and
      regeneration try to mimic intramembranous ossification. In this study, we propose
      to create an in vitro cartilage template as the transient model for in vivo
      endochondral bone formation. The goals of this study are to (1) establish a
      method of growing chondrocytes in a well-characterized macroporous biphasic
      calcium phosphate (MBCP) scaffold and (2) induce maturation of chondrocytes grown
      in the MBCP scaffold. Chondrocytes isolated from chick embryonic tibia were grown
      on MBCP particles and treated with retinoic acid to induce chondrocyte maturation
      and extracellular matrix deposition. Chondrocytes were observed to attach and
      proliferate on the MBCP scaffold. The thickness of the chondrocyte and
      extracellular matrix layer increased in the presence of the retinoid. Alkaline
      phosphatase activity and expression, proteoglycans synthesis, cbfa1 and type I
      collagen mRNA levels also increased in the presence of retinoic acid. These
      results demonstrated for the first time the proliferation, maturation of
      chondrocytes, and matrix deposition on MBCP, suggesting the potential for such
      scaffold in tissue engineering via the endochondral bone formation mechanism.

PMID- 16968169
TI  - Effects of mechanical stimulation on the biomechanics and histology of stem cell
      collagen sponge constructs for rabbit patellar tendon repair.
AB  - The objective of this study was to determine how mechanical stimulation affects
      the biomechanics and histology of stem cell-collagen sponge constructs used to
      repair central rabbit patellar tendon defects. Autogenous tissue-engineered
      constructs were created for both in vitro and in vivo analyses by seeding
      mesenchymal stem cells from 10 adult rabbits at 0.14x10(6) cells/construct in
      type I collagen sponges. Half of these constructs were mechanically stimulated
      once every 5 min for 8 h/day to a peak strain of 4% for 2 weeks. The other half
      remained in an incubator without mechanical stimulation for 2 weeks. Samples
      allocated for in vitro testing revealed that mechanically stimulated constructs
      had 2.5 times the linear stiffness of nonstimulated constructs. The remaining
      paired constructs for in vivo studies were implanted in bilateral full-thickness,
      full-length defects in the central third of rabbit patellar tendons. Twelve weeks
      after surgery, repair tissues were assigned for biomechanical (7 pairs) and
      histologic (3 pairs) analyses. Maximum force, linear stiffness, maximum stress,
      and linear modulus for the stimulated (vs. nonstimulated) repairs averaged 70%
      (vs. 55%), 85% (vs. 55%), 70% (vs. 50%), and 50% (vs. 40%) of corresponding
      values for the normal central third of the patellar tendons. The average force
      elongation curve for the mechanically stimulated repairs also matched the
      corresponding curve for the normal patellar tendons, up to 150% of the peak in
      vivo force values recorded in a previous study. Construct and repair linear
      stiffness and linear modulus were also positively correlated (r = 0.6 and 0.7,
      respectively). Histologically both repairs showed excellent cellular alignment
      and mild staining for decorin and collagen type V, and moderate staining for
      fibronectin and collagen type III. This study shows that mechanical stimulation
      of stem cell-collagen sponge constructs can significantly improve tendon repair
      biomechanics up to and well beyond the functional limits of in vivo loading.

PMID- 16968170
TI  - Modeling the effect of exogenous calcium on keratinocyte and HaCat cell
      proliferation and differentiation using an agent-based computational paradigm.
AB  - In this study we sought to develop a computational modeling paradigm in order to
      describe the influence of calcium on normal and transformed keratinocyte
      proliferation and differentiation. Keratinocytes and HaCat cells were grown in
      monolayer cultures with low and physiologic calcium concentrations, and levels of
      proliferation and involucrin expression were assessed. Both types of cells grew
      as monolayers under a low-calcium environment, and stratified in media with
      physiologic levels of calcium. However, keratinocytes were more proliferative in
      low rather than physiologic levels of calcium, whereas the opposite was true for
      HaCat cells. Normal keratinocytes differentiated as calcium levels increased.
      HaCat cells showed little differentiation at any calcium concentration. However,
      while the computer simulation could be modified to describe the effect of calcium
      on the growth of normal keratinocytes, our findings did not support the
      hypothesis that simply "turning off" the ability of HaCat cells to differentiate
      would account for the growth characteristics of these transformed cells. This
      demonstrates the application of computational modeling to hypothesis testing in
      biological systems.

PMID- 16968171
TI  - A novel simulation model for engineered cartilage growth in static systems.
AB  - A novel mathematical model to simulate the growth of engineered cartilage in
      static systems is proposed. This model is based on material balances for the
      involved species (glycosaminoglycan and collagen, both pertaining to
      extracellular matrix), as well as mass-structured population balance for
      simulating cell growth and its proliferation within the scaffold. This model may
      simulate tissue growth on static culture taking place in Petri dishes, static
      flasks, and well plates for different types of scaffolds (i.e., poly(glycolic
      acid) [PGA], PGA/poly(l-lactic acid), and collagen sponge). This work aimed to
      demonstrate that the model approach proposed in previous works, regarding
      engineered cartilage growth on PGA scaffolds performed in rotating bioreactors,
      may also be applied to different scaffolds and system configurations. In
      particular, the balance equation for simulating collagen production is
      introduced, as well as the use of spatial averaging over the spatial region to
      compare experimental data with the model. Experimental data from the literature
      in terms of cells, glycosaminoglycans, and collagen content have been
      successfully compared with model results, thus demonstrating the validity of the
      proposed model, as well as its predictive capability.

PMID- 16968172
TI  - Fibroblasts accelerate culturing of mucosal substitutes.
AB  - Reconstruction of large mucosal defects of the floor of the mouth is typically
      performed with keratinizing skin. Drawbacks include donor site defects and hair
      bearing of the flaps. Cultured mucosal substitutes (CMSs) have been developed for
      clinical use to replace keratinizing skin. Acellular dermis is often used as a
      dermal carrier for autologous cells, because it reduces wound contraction and is
      easier for the surgeon to handle than, for example, collagen gels. A major
      problem of CMSs using acellular dermis is variation in epidermal quality. To
      improve the quality of the CMSs, human fibroblasts were incorporated into the
      acellular dermis and seeded with human keratinocytes. To study the role of the
      fibroblasts in epidermal morphology and basement membrane formation, CMSs were
      stained for differentiation markers beta1 integrin, cytokeratin 10, and
      involucrin after 1 and 2 weeks in culture. Basement membrane formation was
      analyzed using laminin 5 and collagen IV and VII staining; proliferation was
      analyzed using Ki-67 staining. The epidermises of fibroblast-containing CMSs
      matured faster into a well-organized epithelium than did those that did not
      contain CMSs. A 52.7% increase in basal cells, a 53.5% increase in mitosis index,
      and a 78.0% increase in keratinocyte cell layers were observed. Addition of
      fibroblasts reduced culturing time and enhanced proliferation, maturation, and
      quality of the epidermis.

PMID- 16968173
TI  - Encapsulation of chondrocytes in photopolymerizable styrenated gelatin for
      cartilage tissue engineering.
AB  - We have developed a photopolymerizable styrenated gelatin that can cross-link
      through polymerization induced by irradiation with visible light. The purpose of
      this study was to investigate the feasibility of using photopolymerizable
      styrenated gelatin as a cell carrier in chondrocyte transplantation. As visible
      light activates camphorquinone added as a photoinitiator, free radicals induce
      the polymerization of the gelatin macromer; the styrenated gelatin then becomes
      cross-linked. Rabbit articular chondrocytes were cultured in styrenated gelatin
      hydrogels and also in collagen gels as a control. After being cultured in the
      gels, the cells were collected from both gels and counted. Reverse transcriptase
      polymerase chain reaction, histological examination, and quantification of the
      synthesized glycosaminoglycan were performed. On average, 26% of the embedded
      cells were collected from the gelatin hydrogel immediately after the crosslinking
      reaction. The surviving chondrocytes expressed the mRNA of type II collagen and
      aggrecan core protein and produced a cartilaginous matrix throughout the gelatin
      after 3 weeks. A slightly insufficient accumulation of the matrix was found in
      the internal region of the gelatin hydrogels, suggesting that less permeability
      for nutrients due to the high concentration and closely packed structure resulted
      in less cell viability. Although some limitations became evident, these results
      indicate that it may be possible to use photopolymerizable styrenated gelatin as
      a cell carrier in chondrocyte transplantation.

PMID- 16968174
TI  - High-yield isolation, expansion, and differentiation of rat bone marrow-derived
      mesenchymal stem cells with fibrin microbeads.
AB  - Fibrin microbeads (FMB), made of extensively cross-linked dense and partially
      denatured fibrin, were used as a matrix for efficient isolation of mesenchymal
      stem cells (MSC) from rat bone marrow (BM). After 2 days of incubation of FMB
      with whole BM in suspension, a high number of cells of mesenchymal origin
      attached to the FMB. On the 14th day after their transfer to plastic, the yield
      of the cells isolated via FMB was approximately 3-4 times higher than that
      obtained by currently used protocols based solely on plastic adhesion. This
      implies that the number of MSC in BM may be higher than previously reported. FACS
      analyses and immunostaining showed the mesenchymal characteristics of these cells
      by positive staining for fibronectin, vimentin, CD49E, and CD29. Immediately
      after isolation, less than 20% of the cells still expressed the hematopoietic
      markers CD11b and CD45. Most of these cells were eventually eliminated after
      further expansion of the isolated cells on plastic. Cells isolated via FMB were
      expanded in culture for more than 4 months and could be defined as MSC along this
      time period based on their ability to differentiate into precursors of
      mesenchymal tissues, such as osteogenic, adipogenic, and chondrogenic cells.
      Similar differentiation plasticity was observed in clones derived from single
      cells from whole MSC populations isolated via FMB. Based on our results we
      propose that FMB can serve as a 3-dimensional biodegradable matrix for isolation,
      differentiation, and possibly implantation of MSC for tissue regeneration.

PMID- 16968175
TI  - Engineering of blood vessels from acellular collagen matrices coated with human
      endothelial cells.
AB  - Small-caliber synthetic grafts used for coronary bypass artery grafting are
      compromised by thrombogenicity and accelerated intimal thickening, resulting in
      early graft occlusion. Herein we describe the fabrication and physical properties
      of small-caliber blood vessels using decellularized porcine aortic segments.
      These vessels were further coated with human saphenous vein endothelial cells
      (HSVECs) for future clinical applications. Chemical staining of decellularized
      vessels showed that they preserved their native matrix architecture, including
      several collagen layers in between internal and external elastin layers. The
      burst pressure for the decellularized vessels was higher than 1,000 mmHg. HSVECs,
      seeded on the luminal side, adhered to the matrix and formed a uniform monolayer.
      HSVEC-seeded vessels produced prostaglandin I2 and released vasoactive agents in
      response to the calcium ionophore A23187. These results show that engineered
      blood vessels coated with the host endothelial cells possess morphologic and
      functional characteristics of human small-caliber vessels. Tissue-engineered
      vessels may potentially be useful clinically as vascular grafts.

PMID- 16968176
TI  - Bioreactors for tissue engineering: focus on mechanical constraints. A
      comparative review.
AB  - Considering the current techniques in cell culture, the stimulation of cellular
      proliferation and the formation of bidimensional tissues such as skin are widely
      performed in academic and industrial research laboratories. However, the
      formation of cohesive, organized, and functional tissues by three-dimensional
      (3D) cell culture is complex. A suitable environment is required, which is
      achieved and maintained in a specific bioreactor, a device that reproduces the
      physiological environment (including biochemical and mechanical functions)
      specific to the tissue that is to be regenerated. Bioreactors can also be used to
      apply mechanical constraints during maturation of the regenerating tissue for
      studying and understanding the mechanical factors influencing tissue
      regeneration. In this work, the main types of bioreactors used for tissue
      engineering and regeneration, as well as their most common applications, were
      reviewed and compared. The importance of the mechanical properties applied to the
      scaffolds and the regenerating constructs has been often neglected. This review
      focused on the influence of mechanical stresses and strains during the culture
      period that leads to the final mechanical properties of the construct.

PMID- 16968177
TI  - Human mesenchymal stem cell proliferation and osteogenic differentiation in
      fibrin gels in vitro.
AB  - This study analyzed human mesenchymal stem cell (hMSC) behavior in a fibrin
      sealant. hMSC morphology, proliferation, and osteogenic differentiation were
      analyzed after up to 28 days of incubation in eight different formulations of
      fibrin gels (Tisseel) prepared with various concentrations of fibrinogen complex
      (FC) and thrombin. Cell morphology and distribution within the gels were observed
      by fluorescence microscopy after cell staining with calcein dye. Cell
      proliferation was assessed by measuring the fluorescence intensity of the cell
      suspension stained with calcein dye after dissolution of the gels. A standard
      alkaline phosphatase (ALP) assay, von Kossa staining, and real-time reverse
      transcriptase-polymerase chain reaction (RT-PCR) were used to analyze hMSC
      osteogenic differentiation. Cell behavior varied depending on the gel
      formulation. Proliferation was higher in the formulations containing a low FC
      concentration, but ALP activity was higher in the formulations containing a high
      FC concentration. Variations in thrombin concentration had a lesser effect. Small
      nodules of mineralization were observed at days 21 and 28 in a formulation
      containing a high FC concentration, in addition to a marked increase in bone
      sialoprotein (BSP) gene expression level as well as a lower increase in ALP and
      osteopontin (OPN) levels. However, there was no significant increase in
      osteocalcin (OCN) expression, a late marker of osteogenic differentiation, up to
      day 28. In conclusion, this study demonstrated that hMSC morphology,
      proliferation, and osteogenic differentiation in fibrin gels depended on the
      FC/thrombin ratio. hMSCs appeared to undergo osteogenic differentiation when
      seeded in Tisseel fibrin sealant containing a high FC concentration, but they did
      not fully differentiate into mature osteoblasts.

PMID- 16968178
TI  - Early ligation of the splenic artery in the leaning spleen approach to
      laparoscopic splenectomy.
AB  - BACKGROUND: A variety of approaches have been proposed for laparoscopic
      splenectomy, including the anterior approach, the lateral approach (hanging
      spleen technique), and the semilateral approach (leaning spleen technique). We
      advocate a leaning spleen approach with early ligation of the splenic artery.
      MATERIALS AND METHODS: Since 1997, we have performed 120 laparoscopic
      splenectomies using the leaning spleen approach along with early ligation of the
      splenic artery. The patient is placed in a 70-degree semi-right lateral position.
      The operative steps are: exposure of the lesser sac, control of the splenic
      artery, mobilization of the splenic flexure, division of the splenocolic
      ligament, division of the splenophrenic ligament, hilar mobilization,
      mobilization of the upper pole of the spleen, and removal of the specimen.
      RESULTS: The most common indication for surgery was autoimmune hemolytic anemia
      (35.8%). One patient had severe perisplenitis with extensively vascularized
      adhesions, which led to oozing during surgery obscuring the laparoscopic view,
      requiring conversion to open surgery. The mean spleen diameter was 22.8 cm
      (range, 12.5-37.0 cm) on imaging. The mean operative time was 85 minutes (range,
      54-124 minutes). Concomitant laparoscopic cholecystectomy for pigment stone
      cholelithiasis was performed in 8.3% of the patients. Accessory splenic tissue
      was found in 4.2%. The average hospital stay was 3 days (range, 1-6 days). There
      were no significant postoperative complications. The average follow-up has been
      5.4 years (range, 1 month-9 years). CONCLUSION: In adopting the modification of
      early ligation of the splenic artery in the leaning spleen approach, we believe
      we have helped to advance laparoscopic splenectomy.

PMID- 16968179
TI  - Laparoscopic esophagomyotomy for achalasia without a complementary antireflux
      procedure.
AB  - BACKGROUND: Achalasia is a progressive motility disorder of the esophagus,
      without a definitive cure. The principal method of palliation is myotomy of the
      distal esophagus. We analyzed the 5-year experience at our institution with
      laparoscopic Heller myotomy without an antireflux procedure to determine its
      results, particularly regarding postoperative gastroesophageal reflux. MATERIALS
      AND METHODS: Thirty-three patients, mean age 43 years (range, 29-62 years) with
      clinical, manometric, x-ray, and endoscopic proof of achalasia were operated on
      and followed up for 24 months. Prior to being referred to surgery they had all
      undergone at least one pneumatic balloon dilation. The operative technique was a
      7-cm myotomy that included the lower esophageal sphincter but did not exceed 5 mm
      of the gastric cardia. Follow-up consisted of clinical observation,
      cineesophagography, and 24-hour pHmetry. RESULTS: All patients reported
      satisfactory to excellent results regarding dysphagia and no heartburn two years
      after the operation. The 24-hour pHmetry and the radiographic investigation
      showed no evidence of gastroesophageal reflux. CONCLUSION: It seems that the risk
      of gastroesophageal reflux is very low when the cardiomyotomy does not exceed the
      length of 5 mm. Our results are in accordance with other observational studies as
      well as larger cohort and meta-analysis studies. Prospective randomized studies
      are needed to clarify the role of an antireflux procedure after laparoscopic
      Heller myotomy.

PMID- 16968180
TI  - Emergency laparoscopically assisted right hemicolectomy for obstructing right
      sided colon carcinoma.
AB  - BACKGROUND: We report our preliminary experience in urgent laparoscopically
      assisted right hemicolectomy for obstructing right-sided colon carcinoma.
      MATERIALS AND METHODS: From January to April 2005, seven consecutive patients
      with obstructing right-sided colon carcinoma underwent emergency laparoscopically
      assisted right or extended right hemicolectomy. Patient demographic data,
      operative details, and short-term clinical outcomes were prospectively collected
      and analyzed. RESULTS: The median duration of obstructing symptoms prior to
      admission was 3 days (range, 1-6 days). Two patients underwent palliative
      resection and five patients underwent curative resection. The median operative
      time was 180 minutes (range, 125-350 minutes). There were no conversions to the
      open procedure. Median blood loss was 30 mL (range, negligible-300 mL). The
      median times to resuming diet, first bowel motion, and full ambulation were 4
      days (range, 3-10 days), 5 days (range, 3-7 days), and 4 days (range, 4-5 days),
      respectively. The median duration of hospital stay was 7 days (range, 6-19 days).
      One patient with ischemic heart disease developed acute coronary syndrome
      postoperatively and died on postoperative day 19. The remaining patients had no
      complications. The median tumor length was 3.5 cm (range, 2-5 cm) and the median
      number of lymph nodes removed was 17 (range, 16-36). CONCLUSION: Emergency
      laparoscopically assisted right hemicolectomy for obstructing right-sided colon
      carcinoma is feasible and safe, with favorable short-term clinical outcomes and
      an acceptable number of lymph nodes removed.

PMID- 16968181
TI  - Management of acute upper gastrointestinal bleeding in a district hospital.
AB  - BACKGROUND: This study was conducted to assess the management of acute upper
      gastrointestinal bleeding in a district hospital and to compare these results
      with national guidelines and the published literature. MATERIALS AND METHODS:
      This prospective and retrospective study included 112 patients, mean age 66
      years, who presented with acute upper gastrointestinal bleeding between July 2004
      and February 2005. All patients were assigned a Rockall risk assessment score.
      RESULTS: The surgical on-call teams managed all the patients according to an
      agreed protocol. Forty-nine patients had a Rockall score > or =4. Endoscopy was
      performed in all patients, with 60% accomplished within the first 24 hours. The
      most common cause found was peptic ulcer (30%). Therapeutic endoscopy was
      undertaken in 10 patients (9%) with a success rate of 70%. Open surgery was
      performed in 3 patients. One patient died after having surgery and the Rockall
      score was >5. Of the patients admitted with acute upper gastrointestinal
      bleeding, 90.2% were discharged without complication. Eleven patients died (9.8%)
      and all of them from the high risk group with Rockall scores > or =5. Their mean
      hospital stay was 17.8 days (range, 2-43 days). CONCLUSION: High-standard results
      in acute upper gastrointestinal bleeding can be achieved in a district hospital.
      The management, including the use of the operating theater facilities with
      operative and anesthetic support, was safe and efficient. A 24-hour-a-day
      endoscopy service is important to achieve early diagnosis and to plan management.
      A protocol and early endoscopy improve clinical outcome and reduce mortality,
      which occurred mostly among elderly patients with high risk scores. It is
      advisable to introduce the Rockall scoring system in practice.

PMID- 16968182
TI  - Degloving of the renal capsule: a rare complication of laparoscopic live donor
      nephrectomy.
AB  - Laparoscopic live donor nephrectomy is becoming the procedure of choice for
      kidney procurement. In the course of 172 laparoscopic procurements, degloving of
      the renal capsule, a rare complication believed to be related to the method of
      extraction of the kidney, was encountered in 2 patients (1.2%). The complication
      was noted after revascularization of the kidney. A capsulotomy was performed to
      evacuate the subcapsular hematoma. No adverse effect was noted in the
      postoperative period in the transplanted kidneys.

PMID- 16968183
TI  - Is laparoscopic cholecystectomy safe and acceptable as a day case procedure?
AB  - BACKGROUND: This study reviewed the results of performing day case laparoscopic
      cholecystectomy to assess the feasibility and safety of the procedure as a day
      case. MATERIALS AND METHODS: This is a prospective study of 150 day case
      laparoscopic cholecystectomies performed between September 1999 and December 2004
      under the care of the senior author. The results of a follow-up questionnaire to
      assess post-discharge clinical course and patient satisfaction were analyzed. All
      patients had commenced eating and drinking and were fully mobile before discharge
      home. The length of hospital stay was 4-8 hours. RESULTS: The mean age of the
      patients was 43 years; 134 patients had an American Society of Anesthesiologists
      grade I, the remaining 16 patients were grade II. The mean operative time was 41
      minutes. There were no conversions to open procedures. There was no bleeding, no
      visceral injury, and no mortality. There was one admission directly from the day
      surgical unit (admission rate of 0.6%), but no readmission following discharge.
      No patients were admitted due to postoperative nausea or pain. Ninety-nine (66%)
      of 150 patients responded to our questionnaire: 97% were satisfied about the
      information they had received. Patients rated their satisfaction with the
      procedure as follows: 75% excellent, 21% good, 3% satisfied, and 1 patient un
      satisfied. Ninety-four percent of the patients would recommend the procedure as a
      day case. CONCLUSION: Day case laparoscopic cholecystectomy is safe, feasible,
      and cost-effective when patients are carefully selected. It provides good patient
      satisfaction.

PMID- 16968184
TI  - Laparoscopic removal of a retained intra-abdominal ribbon malleable retractor
      after 14 years.
AB  - We report a case of the laparoscopic removal of a 33 x 5 cm ribbon malleable
      retractor retained intra-abdominally for 14 years. Plain films revealed a
      radiopaque object in the midline abdomen consistent with a metallic device. This
      was a ribbon malleable retractor which was subsequently removed laparoscopically
      without complication. Laparoscopic surgery should be considered in the removal of
      foreign bodies from the abdominal cavity.

PMID- 16968185
TI  - Laparoscopic duodenojejunostomy for superior mesenteric artery syndrome.
AB  - Superior mesenteric artery syndrome (Wilkie's syndrome) causes acute or chronic
      compression of the third part of the duodenum. Initially conservative treatment
      is tried, but on failure of treatment, duodenojejunostomy is the procedure of
      choice, usually done by open surgery. We present a case of superior mesenteric
      artery syndrome in which the duodenojejunostomy was done laparoscopically.

PMID- 16968186
TI  - Multilocular flank abscess due to stone migration following laparoscopic
      cholecystectomy with spillage of gallstones.
AB  - We report a case of a patient who presented with a large flank abscess 18 months
      after laparoscopic cholecystectomy. The patient underwent repeated percutaneous
      drainage but the abscess recurred. Further evaluation with ultrasound revealed
      subcutaneous tracks from the flank leading to the abdominal cavity and suspected
      stones in one of the tracks. Laparoscopy revealed dense adhesions at the level of
      the right gutter leading to a retroperitoneal track heading over to the flank.
      The tracks were partially opened, debrided, and two gallstones were retrieved
      from one of the retroperitoneal tracks. The patient's recovery was uneventful.
      This case demonstrates the potential migration of dropped gallstones to
      extraperitoneal sites leading to infectious complications. Careful dissection of
      the gallbladder with an attempt not to rupture it is important in order to
      prevent this complication. Once rupture does occur, efforts should be made to
      retrieve dropped stones from the peritoneal cavity. Patients presenting with
      intra- or extraperitoneal abscesses following laparoscopic cholecystectomy and no
      obvious source of infection should be evaluated for dropped stones.

PMID- 16968187
TI  - Retroperitoneoscopic live donor nephrectomy in a patient with a double inferior
      vena cava.
AB  - BACKGROUND: Vascular anomalies are considered a contraindication for laparoscopic
      live donor nephrectomy. We report a successful hand-assisted retroperitoneoscopic
      live donor nephrectomy from a donor with a double inferior vena cava. MATERIALS
      AND METHODS: A 37-year-old woman wanted to donate a kidney to her 44-year-old
      boyfriend who had hypertensive nephropathy. Preoperative donor imaging showed a
      double inferior vena cava. Each renal vein drains into the ipsilateral inferior
      vena cava division, making the left renal vein short. A single renal artery,
      vein, and ureter were noted on both sides. A hand-assisted retroperitoneoscopic
      left nephrectomy was performed. Blood loss was minimal and the warm ischemia time
      was 2 minutes. Renal transplantation was performed with good initial perfusion
      and urine output. Cold ischemia and rewarming time was 25 minutes. RESULTS: The
      donor postoperative period was uneventful with infrequent need for pain relief.
      The donor was discharged in good condition 3 days postoperatively. The donor's
      kidney functions were within the normal range at follow-up 4 months
      postoperatively. The recipient was discharged in good condition 7 days
      postoperatively. The recipient is alive with good graft function and unremarkable
      complications at 4 month follow-up. CONCLUSION: Although vascular anomalies
      present a surgical challenge, we have shown the feasibility of performing hand
      assisted retroperitoneoscopic live donor nephrectomy in a donor with a double
      vena cava and short renal vein. With comprehensive preoperative assessment,
      laparoscopic live donor nephrectomy can be done safely in donors with anatomical
      anomalies. This may increase the number of living donor kidney transplants as it
      offers lower postoperative morbidity and economic disincentives for potential
      donors.

PMID- 16968188
TI  - Composite mesh repair of a large paraesophageal hiatal hernia.
AB  - We describe the first experience in Italy with a new pre-cut composite
      polytetrafluoroethylene (PTFE)/expanded PTFE (ePTFE) prosthesis designed for the
      hiatal region. A 78-year-old female patient with a large paraesophageal hiatal
      hernia with migration of the left transverse colon inside the hiatal defect (type
      IV hernia) received laparoscopic repair by means of the composite V-shaped mesh.
      The procedure was completed laparoscopically and a partial fundoplication was
      performed. A favorable outcome was assessed by barium swallow radiograms
      performed on postoperative day 7. A complete resolution of the symptoms was noted
      at follow-up 1 month postoperatively. This report confirms the feasibility,
      effectiveness, and added advantages of the composite V-shaped mesh in tension
      free repair of a large hiatal hernia.

PMID- 16968189
TI  - Vesicovaginal fistula with secondary vaginal stones.
AB  - PURPOSE: We report a rare case of a vesicovaginal fistula associated with
      secondary vaginal stones that was managed totally endoscopically. MATERIALS AND
      METHODS: A 52-year-old woman presented with urinary incontinence and perineal
      pain. On subsequent evaluation, we found a vesicovaginal fistula associated with
      secondary vaginal stones caused by a retained gauze. Management involved
      vaginoscopy, intracorporeal shock wave lithotripsy for vaginal stones, and
      removing retained medical gauze. We performed cystoscopy, laparoscopic cystotomy,
      transabdominal Foley catheterization of the vesicovaginal fistula for traction,
      injection of diluted adrenaline-saline solution for better dissection, dissection
      of the bladder from the vagina, tension-free closure of the bladder and vaginal
      defects, and closure of the cystotomy. RESULTS: Operative time was 155 minutes
      and blood loss was 60 mL. The patient was discharged on postoperative day 3, and
      catheterization time was 14 days. At 3-month follow-up, the patient was fully
      continent. CONCLUSION: To our knowledge, this is the first reported case of a
      vesicovaginal fistula associated with secondary vaginal stones which was managed
      totally endoscopically. We believe that this is a feasible and efficacious
      approach for the management of such cases.

PMID- 16968190
TI  - Overhead analysis in a surgical practice: a brief communication.
AB  - Evaluating overhead is an essential part of any business, including that of the
      surgeon. By examining each component of overhead, the surgeon will have a better
      grasp of the profitability of his or her practice. The overhead discussed in this
      article includes health insurance, overtime, supply costs, rent, advertising and
      marketing, telephone costs, and malpractice insurance. While the importance of
      evaluating and controlling overhead in a business is well understood, few know
      that overhead increases do not always imply increased expenses. National
      standards have been provided by the Medical Group Management Association. One
      method of evaluating overhead is to calculate the amount spent in terms of
      percent of net revenue. Net revenue includes income from patients, from interest,
      and from insurers less refunds. Another way for surgeons to evaluate their
      practice is to calculate income and expenses for two years, then calculate the
      variance between the two years and the percentage of variance to see where they
      stand.

PMID- 16968191
TI  - Lymphography prior to laparoscopic Palomo varicocelectomy to prevent
      postoperative hydrocele.
AB  - BACKGROUND: We report our experience with preoperative lymphography to identify
      and perioperatively preserve the ligature of the lymphatic vessels to reduce the
      incidence of postoperative testicular hydrocele in patients undergoing
      laparoscopic Palomo varicocelectomy for adolescent varicocele. MATERIALS AND
      METHODS: Twenty-seven consecutive patients with varicocele had preoperative
      lymphography. The mean age was 13.5 years (range, 8-18 years) and the mean grade
      of varicocele was III. We performed lymphography with intrascrotal isosulfan
      blue. The laparoscopic Palomo procedure was successfully carried out in all
      patients. RESULTS: In 17 patients (63%) we were able to identify and conserve the
      lymphatic vessels by lymphography. Mean follow-up was 9.5 months (range, 6-24
      months). None of the 27 patients had a recurrence. None of the 17 patients with
      positive lymphography had a testicular hydrocele. One of the 10 remaining
      patients developed a sizable hydrocele. CONCLUSION: Preoperative lymphography
      prior to laparoscopic Palomo varicocelectomy is a simple and feasible method for
      preventing testicular hydrocele. However, the method should be standardized to
      identify the exact site, the correct level of injection of blue dye, and to
      determine the optimal time to perform lymphography prior to the procedure.

PMID- 16968192
TI  - Pediatric thoracoscopic training in an experimental pleural empyema rabbit model.
AB  - BACKGROUND: Thoracoscopy has proved to be effective in the treatment of stage 2
      (fibrinopurulent) empyema, but this technique requires different abilities from
      those needed in open surgery. The aim of this study is to evaluate the usefulness
      of an experimental empyema in rabbits as a thoracoscopic training model.
      MATERIALS AND METHODS: Twenty New Zealand rabbits were anesthetized with
      acepromazine and ketamine. A Veress needle was introduced into the pleural space,
      and a turpentine and saline solution were injected. Twenty-four hours later, 1016
      colony-forming units of Escherichia coli and 1 g of agar in 1 mL of saline
      solution were injected. The rabbits were operated on 96 hours after bacterial
      injection by 30 pediatric surgeons attending a hands-on pediatric laparoscopic
      course. The contralateral lung was selectively intubated and three ports were
      placed to perform an empyema debridement. The surgeons evaluated the model using
      subjective criteria from an evaluation form. RESULTS: One animal died (5%) and 2
      (10%) did not form empyema. The other 17 rabbits (85%) presented with a
      fibrinopurulent empyema. All usual surgical steps could be performed. As regards
      the surgeons' opinion of the model, 23 (76.7%) considered it very good while 7
      (23.3%) thought it was good. Twenty-three (76.7%) answered that the empyema stage
      was correct for thoracoscopic treatment. CONCLUSION: As reflected by our
      experience and the survey completed by the 30 pediatric surgeons, this empyema
      model in rabbits is very useful for thoracoscopic training.

PMID- 16968193
TI  - Appendicostomy stomas and antegrade colonic irrigation after laparoscopic
      antegrade continence enema.
AB  - BACKGROUND: Children with spina bifida, high anorectal anomalies, or neuronal
      intestinal dysplasia who are treated with a laparoscopic antegrade continence
      enema to achieve a socially acceptable level of fecal continence sometimes have
      problems with the stoma and its catheterization. The goal of this study was to
      determine the nature and incidence of these problems, and their relationship to
      the underlying condition. MATERIALS AND METHODS: A retrospective review of the
      hospital case notes of 74 consecutive patients who had a laparoscopic antegrade
      continence enema was undertaken. RESULTS: The laparoscopic antegrade continence
      enema procedure is well tolerated but is associated with a variety of usually
      minor complications including stomal stenosis, leakage, peristomal infection,
      granulation tissue overgrowth, mucosal prolapse, abdominal discomfort during
      irrigation, appendiceal false passage, and ineffective irrigation. Surgical
      revision of the stoma was required in 19% of the cases in this study, usually
      because of stenosis and skin overgrowth. Ongoing problems achieving colonic
      emptying were most likely to occur in patients with an anorectal malformation.
      CONCLUSION: Overall, the laparoscopic antegrade continence enema provides an
      effective method of facilitating emptying of the bowel. However, it has a high
      incidence of minor troublesome problems, with stenosis and skin overgrowth of the
      stoma being the most common. Younger children tend to have more complications and
      difficulty performing effective irrigation. Children with anorectal malformations
      were more likely to require surgical revision of the stoma, and often needed
      ongoing manual evacuation and bowel washouts despite the laparoscopic antegrade
      continence enema.

PMID- 16968194
TI  - Adverse effects of increased intra-abdominal pressure on small bowel structure
      and bacterial translocation in the rat.
AB  - BACKGROUND: The purpose of this study was to evaluate the effects of elevated
      intra-abdominal pressure (IAP) on intestinal structures and bacterial
      translocation in the rat. MATERIALS AND METHODS: Forty-two male Sprague-Dawley
      rats were randomly divided into three experimental groups of 14 rats each: the
      sham group underwent insertion of a balloon-tipped catheter; the IAP-15 group was
      subjected to a 15 mm Hg pneumoperitoneum for 60 minutes; and the IAP-25 group was
      subjected to a 25 mm Hg pneumoperitoneum for 60 minutes. Intestinal structural
      changes (bowel circumference, overall bowel and mucosal weight, mucosal DNA and
      protein, villus height, and crypt depth) and bacterial translocation to
      mesenteric lymph nodes, liver, spleen, portal blood, and peripheral blood were
      determined 24 hours following pneumoperitoneum. RESULTS: IAP-15 and IAP-25 rats
      demonstrated a significant decrease in: bowel and mucosal weight in the duodenum,
      jejunum, and ileum; mucosal DNA and protein in the jejunum and ileum; villus
      height in the jejunum: and crypt depth in the jejunum and ileum compared to the
      sham rats. Bacterial translocation was demonstrated in 60% of IAP-15 rats and in
      80% of IAP-25 rats. CONCLUSION: Elevated IAP results in mucosal injury of the
      gut, causing mucosal hypoplasia, and increases bacterial translocation.

PMID- 16968195
TI  - Laparoscopy as an adjunct to peritoneal drainage in perforated necrotizing
      enterocolitis.
AB  - Intestinal perforation in very low birth weight infants with necrotizing
      enterocolitis has a high morbidity and mortality. We report the use of
      laparoscopy on day 30 of life in the treatment of a very low birth weight infant
      (900 g) with perforated necrotizing enterocolitis. The question of laparotomy
      versus peritoneal drain is ongoing. Laparoscopy may have a major role to play in
      the answer to this debate. The versatility of laparoscopy enables good
      visualization of the bowel and organs: a drain can be placed in a port site if
      there is no fecal contamination and a more conservative approach is warranted, or
      a conversion to a laparotomy can be undertaken if there are obvious feces or
      necrotic bowel. We feel that laparoscopy in the initial evaluation of necrotizing
      enterocolitis is invaluable, and can avoid potentially unnecessary surgery in an
      already extremely unwell infant.

PMID- 16968196
TI  - Laparoscopic partial splenectomy using radiofrequency ablation for nonparasitic
      splenic cysts in two children.
AB  - Nonparasitic splenic cysts are uncommon lesions, for which partial splenectomy
      offers a definitive treatment while preserving splenic function. We report the
      use of radiofrequency energy for laparoscopic partial splenectomy to treat two
      children with nonparasitic splenic cysts by creating a 1-cm thick coagulated
      parenchyma resection plane, allowing bloodless splenic transection. This approach
      spares the need for blood transfusions, reduces hospital stay, and offers great
      promise for partial splenectomy in children.

PMID- 16968197
TI  - Two cases of thoracoscopic resection of esophageal duplication in children.
AB  - We report two cases of thoracoscopic resection of esophageal duplication cysts.
      Both patients underwent successful thoracoscopic excision. They were discharged
      on postoperative day 2 and 4, respectively. They made uneventful recoveries and
      were completely asymptomatic at 1-month followup. One child was lost to long-term
      follow-up. In the other child, barium swallow study 10 months after surgery
      demonstrated a pseudodiverticulum at the site of cyst excision. Thoracoscopic
      resection of esophageal duplications is safe. Complete excision is possible even
      if the cyst shares a common muscular wall with the esophagus. Pseudodiverticulum
      may develop at the site of excision: follow- up is necessary and consideration
      should be given to closure of the muscular defect at the time of excision. To
      help avoid esophageal injury and, should it occur, recognize esophageal
      perforation, we recommend performing the dissection under intraesophageal
      endoscopic supervision.

PMID- 16968198
TI  - Robotic-assisted laparoscopic correction of pediatric retrocaval ureter.

PMID- 16968199
TI  - Laparoscopic resection of an axially torted Meckel's diverticulum in a 13-year
      old.
AB  - We report an unusual case of acute abdomen due to axial torsion and infarction of
      a Meckel's diverticulum in a 13-year-old boy and illustrate the versatility of
      laparoscopy in the diagnosis and management of acute surgical abdomen in
      children. We believe that this is only the third case reported in a child of
      torsion of a Meckel's diverticulum and the first to be managed by laparoscopic
      resection.

PMID- 16968200
TI  - How reliable is intracorporeal laparoscopic knot tying?
AB  - BACKGROUND: Are knots tied laparoscopically as reliable as those tied in open
      surgery? The aim of our study was to try to answer this question. MATERIALS AND
      METHODS: Using a standardized technique, one senior laparoscopic surgeon tied 3
      suture materials using 3 methods of knotting: hand, instrument, and laparoscopic
      (in a simulator). The tension in the knots was measured using a tension gauge at
      the time of knotting and 5 minutes later. The surgeon was blinded to the value.
      The experiment was repeated 4 times. The 36 sutures were then analyzed using a
      materials-testing machine. The force achieved prior to breakage, the extension,
      and the breaking points were recorded. The scientist performing the analysis was
      blinded as to the method of tying and tensions produced. RESULTS: There were no
      significant differences in tension at 5 minutes between suture materials or
      method of knot tying. The mean extension achieved prior to breakage for 33
      sutures was 29.71 mm with a force of 16.09 N. In 3 sutures the knot slipped
      completely while tension was being increased, thus no measure of breakage force
      could be obtained. These 3 sutures were monofilament and tied laparoscopically.
      CONCLUSION: There were no significant changes in suture tension after 5 minutes
      regardless of material or method of knot tying. Three of the 12 knots tied
      laparoscopically came undone under strain testing. All 3 knots were monofilament
      suture. This may have important implications when choosing suture material.
      Further studies are planned to expand the analysis of different knotting
      techniques with different suture materials.

PMID- 16968202
TI  - The role of allatostatins in juvenile hormone synthesis in insects and
      crustaceans.
AB  - Allatostatins are pleiotropic neuropeptides for which one function in insects is
      the inhibition of juvenile hormone synthesis. Juvenile hormone, an important
      regulator of development and reproduction in insects, is produced by the corpora
      allata. Mandibular organs, the crustacean homologs of insect corpora allata,
      produce precursors of juvenile hormone with putatively similar functions. Three
      types of allatostatins in insects have been isolated: FGLamides, W(X)(6)Wamides,
      and PISCFs. All act rapidly and reversibly; however, although these types occur
      in all groups of insects studied, they act as inhibitors of juvenile hormone
      production in only some groups. Only the FGLamide-type peptides have been
      isolated in crustaceans, in which they may function to stimulate production of
      hormone by the mandibular glands, as occurs in early cockroach embryos. Much
      remains to be learned in order to understand the role of allatostatins in the
      modulation of hormone production.

PMID- 16968203
TI  - Group decision making in nest-site selection among social insects.
AB  - The choice of a new nest site is ecologically critical for an insect colony. In
      swarm-founding social insects, or those that move as colonies from one site to
      another, this choice is one of the best-available examples of a distributed,
      nonhierarchical decision-making process in animals. In the few species of ants
      and bees that have been studied in detail, the main features of this collective
      decision making are strikingly similar, although some differences occur.
      Individual scouts discover potential nest sites and integrate multiple properties
      of these sites into assessments of their quality. The discovered sites then
      compete for a limited pool of nest-site scouts, and attrition of less-favored
      sites occurs by several mechanisms. Finally, the mass movement of the colony to
      the new site is triggered by a quorum-sensing mechanism when sufficient scouts
      are present at one of the alternatives. Movement itself is coordinated by
      different mechanisms in different insects.

PMID- 16968204
TI  - Biology of the bed bugs (Cimicidae).
AB  - The cimicids, or bed bugs, belong to a highly specialized hematophagous taxon
      that parasitizes primarily humans, birds, and bats. Their best-known member is
      the bed bug, Cimex lectularius. This group demonstrates some bizarre but
      evolutionarily important biology. All members of the family Cimicidae show
      traumatic insemination and a suite of female adaptations to this male trait.
      Cimicids therefore constitute an ideal model system for examining the extreme
      causes and consequences of sexual selection. Our dual goal in re-examining the
      extensive literature on this group is to identify issues relevant to pest
      control, such as dispersal ecology and the recent global spread, and to
      understand the selective forces that have shaped the unique aspects of this
      insect's biology.

PMID- 16968205
TI  - Insect conservation: a synthetic management approach.
AB  - Threats to insect diversity range from habitat loss and invasive alien organisms
      to environmental contamination and biological control. Many of the threats are
      synergistic, with the joint impact of habitat loss and global climate change
      being highly adversely synergistic. Recent research on insect conservation has
      elucidated some basic principles for conservation management. There are six basic
      principles that are interrelated and together provide guidelines for synthetic
      conservation management of insects. They are maintain reserves (principle 1),
      maintain as much quality landscape heterogeneity as possible (principle 2),
      reduce contrast between remnant patches and neighboring disturbed patches
      (principle 3), outside reserves, introduce land sparing (principle 4), simulate
      natural conditions and disturbance (principle 5), and connect similar patches of
      quality habitat (principle 6). These six principles constitute a coarse-filter,
      landscape approach. Permeating all six is the principle of maintaining healthy
      population levels, which require the combined support of the metapopulation trio
      of large patch (habitat) size, good patch quality, and reduced patch isolation.
      In addition to these six coarse-filter principles is an overlay of the fine
      filter, species approach, in which particular species are given focused attention
      and management.

PMID- 16968206
TI  - The use of push-pull strategies in integrated pest management.
AB  - Push-pull strategies involve the behavioral manipulation of insect pests and
      their natural enemies via the integration of stimuli that act to make the
      protected resource unattractive or unsuitable to the pests (push) while luring
      them toward an attractive source (pull) from where the pests are subsequently
      removed. The push and pull components are generally nontoxic. Therefore, the
      strategies are usually integrated with methods for population reduction,
      preferably biological control. Push-pull strategies maximize efficacy of behavior
      manipulating stimuli through the additive and synergistic effects of integrating
      their use. By orchestrating a predictable distribution of pests, efficiency of
      population-reducing components can also be increased. The strategy is a useful
      tool for integrated pest management programs reducing pesticide input. We
      describe the principles of the strategy, list the potential components, and
      present case studies reviewing work on the development and use of push-pull
      strategies in each of the major areas of pest control.

PMID- 16968208
TI  - Mediation analysis.
AB  - Mediating variables are prominent in psychological theory and research. A
      mediating variable transmits the effect of an independent variable on a dependent
      variable. Differences between mediating variables and confounders, moderators,
      and covariates are outlined. Statistical methods to assess mediation and modern
      comprehensive approaches are described. Future directions for mediation analysis
      are discussed.

PMID- 16968209
TI  - Ostracism.
AB  - In this review, I examine the social psychological research on ostracism, social
      exclusion, and rejection. Being ignored, excluded, and/or rejected signals a
      threat for which reflexive detection in the form of pain and distress is adaptive
      for survival. Brief ostracism episodes result in sadness and anger and threaten
      fundamental needs. Individuals then act to fortify or replenish their thwarted
      need or needs. Behavioral consequences appear to be split into two general
      categories: attempts to fortify relational needs (belonging, self-esteem, shared
      understanding, and trust), which lead generally to prosocial thoughts and
      behaviors, or attempts to fortify efficacy/existence needs of control and
      recognition that may be dealt with most efficiently through antisocial thoughts
      and behaviors. Available research on chronic exposure to ostracism appears to
      deplete coping resources, resulting in depression and helplessness.

PMID- 16968210
TI  - The representation of object concepts in the brain.
AB  - Evidence from functional neuroimaging of the human brain indicates that
      information about salient properties of an object-such as what it looks like, how
      it moves, and how it is used-is stored in sensory and motor systems active when
      that information was acquired. As a result, object concepts belonging to
      different categories like animals and tools are represented in partially
      distinct, sensory- and motor property-based neural networks. This suggests that
      object concepts are not explicitly represented, but rather emerge from weighted
      activity within property-based brain regions. However, some property-based
      regions seem to show a categorical organization, thus providing evidence
      consistent with category-based, domain-specific formulations as well.

PMID- 16968211
TI  - Partitioning the domain of social inference: dual mode and systems models and
      their alternatives.
AB  - Recent decades of theorizing about social inference phenomena have seen a variety
      of models that partitioned the underlying processes into two qualitatively
      distinct types whose specific nature was depicted differently in the different
      frameworks. The present article reviews major such partitioning efforts as well
      as their proposed alternatives, and discusses their unique features, their
      commonalities, and the conceptual and empirical issues that they raise.

PMID- 16968213
TI  - mTOR pathway as a target in tissue hypertrophy.
AB  - Recent work has shown that the mTOR (mammalian target of rapamycin) pathway is an
      integral cell growth regulator. The mTOR pathway involves two functional
      complexes, TORC1 and TORC2, which have been defined by both their association
      with raptor or rictor, respectively, and their sensitivity to short-term
      rapamycin inhibition. Loss of tumor suppressors TSC1 or TSC2 leads to aberrant
      activation of TORC1, which has been implicated in the control of cell size. As a
      result, both physiologic and pathologic tissue hypertrophy are associated with
      TORC1 activation. Some clinical examples include skeletal and cardiac muscle
      hypertrophy, vascular restenosis, and compensatory nephrotic hypertrophy.
      Clarification of the mTOR pathway may lead to increased understanding of both the
      etiology and consequences of aberrant cell size regulation. This review covers
      some of the biochemical regulation of the mTOR pathway that may be important to
      the regulation of cell size, and it will present several potential clinical
      applications where the control of cell size may be biologically significant.

PMID- 16968212
TI  - Diseases caused by defects in the visual cycle: retinoids as potential
      therapeutic agents.
AB  - Absorption of a photon by an opsin pigment causes isomerization of the
      chromophore from 11-cis-retinaldehyde to all-trans-retinaldehyde. Regeneration of
      visual chromophore following light exposure is dependent on an enzyme pathway
      called the retinoid or visual cycle. Our understanding of this pathway has been
      greatly facilitated by the identification of disease-causing mutations in the
      genes coding for visual cycle enzymes. Defects in nearly every step of this
      pathway are responsible for human-inherited retinal dystrophies. These retinal
      dystrophies can be divided into two etiologic groups. One involves the impaired
      synthesis of visual chromophore. The second involves accumulation of cytotoxic
      products derived from all-trans-retinaldehyde. Gene therapy has been successfully
      used in animal models of these diseases to rescue the function of enzymes
      involved in chromophore regeneration, restoring vision. Dystrophies resulting
      from impaired chromophore synthesis can also be treated by supplementation with a
      chromophore analog. Dystrophies resulting from the accumulation of toxic pigments
      can be treated pharmacologically by inhibiting the visual cycle, or limiting the
      supply of vitamin A to the eyes. Recent progress in both areas provides hope that
      multiple inherited retinal diseases will soon be treated by pharmaceutical
      intervention.

PMID- 16968214
TI  - Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway.
AB  - Keap1-Nrf2-ARE signaling plays a significant role in protecting cells from
      endogenous and exogenous stresses. The development of Nrf2 knockout mice has
      provided key insights into the toxicological importance of this pathway. These
      mice are more sensitive to the hepatic, pulmonary, ovarian, and neurotoxic
      consequences of acute exposures to environmental agents and drugs, inflammatory
      stresses, as well as chronic exposures to cigarette smoke and other carcinogens.
      Under quiescent conditions, the transcription factor Nrf2 interacts with the
      actin-anchored protein Keap1, largely localized in the cytoplasm. This quenching
      interaction maintains low basal expression of Nrf2-regulated genes. However, upon
      recognition of chemical signals imparted by oxidative and electrophilic
      molecules, Nrf2 is released from Keap1, escapes proteasomal degradation,
      translocates to the nucleus, and transactivates the expression of several dozen
      cytoprotective genes that enhance cell survival. This review highlights the key
      elements in this adaptive response to protection against acute and chronic cell
      injury provoked by environmental stresses.

PMID- 16968216
TI  - Historical and conceptual background of self-organization by reactive processes.
AB  - Order, form, pattern and organization are properties central to much living
      matter. The physicochemical processes by which an initially homogeneous solution
      of reacting chemicals or biochemicals might self-organize is hence a question of
      fundamental biological importance. In most cases, solutions of reacting chemicals
      in a test-tube do not self-organize. Because of this, for many years, it was not
      thought possible that reactive processes could result in self-organization.
      However, progressively over the last hundred years, it has been shown that this
      is not always the case, and under certain conditions, the combination of reaction
      with molecular diffusion can lead to macroscopic self-organization. In 'complex'
      systems comprised of populations of strongly coupled elements, new 'emergent'
      properties, such as self-organization, arise by way of the dynamics of the
      system. Self-organizing reaction-diffusion systems form a specific type of
      complex system. Here, I will give a personal overview of the conceptual and
      historical background to this approach with an emphasis on biological self
      organization.

PMID- 16968217
TI  - Microtubules viewed as molecular ant colonies.
AB  - Populations of ants and other social insects self-organize and develop 'emergent'
      properties through stigmergy in which individual ants communicate with one
      another via chemical trails of pheromones that attract or repulse other ants. In
      this way, sophisticated properties and functions develop. Under appropriate
      conditions, in vitro microtubule preparations, initially comprised of only
      tubulin and GTP, behave in a similar manner. They self-organize and develop other
      higher-level emergent phenomena by a process where individual microtubules are
      coupled together by the chemical trails they produce by their own reactive
      growing and shrinking. This behaviour is described and compared with the
      behaviour of ant colonies. Viewing microtubules as populations of molecular ants
      may provide new insights as to how the cytoskeleton may spontaneously develop
      high-level functions. It is plausible that such processes occur during the early
      stages of embryogenesis and in cells.

PMID- 16968219
TI  - The exosome: a macromolecular cage for controlled RNA degradation.
AB  - The exosome, a large multisubunit complex with exoribonucleic activity, emerges
      as the central 3' RNA degradation and processing factor in eukaryotes and
      archaea. But how are the many RNA substrates of the exosome degraded in a
      processive, yet controlled manner? Recent functional and structural progress
      shows that the exosome is a macromolecular cage, where the nuclease active sites
      are situated in a central processing chamber. A narrow entry pore controls access
      to the active sites in the processing chamber and prevents uncontrolled RNA
      decay. The emerging mechanism of exosome function suggests a strikingly parallel
      architectural concept to protein degradation by proteasomes.

PMID- 16968220
TI  - The cell biology of secondary endosymbiosis--how parasites build, divide and
      segregate the apicoplast.
AB  - Protozoan parasites of the phylum Apicomplexa harbour a chloroplast-like
      organelle, the apicoplast. The biosynthetic pathways localized to this organelle
      are of cyanobacterial origin and therefore offer attractive targets for the
      development of new drugs for the treatment of malaria and toxoplasmosis. The
      apicoplast also provides a unique system to study the cell biology of
      endosymbiosis. This organelle is the product of secondary endosymbiosis, the
      marriage of an alga and an auxotrophic eukaryote. This origin has led to a
      fascinating set of novel cellular mechanisms that are clearly distinct from those
      employed by the plant chloroplast. Here we explore how the apicoplast interacts
      with its 'host' to secure building blocks for its biogenesis and how the
      organelle is divided and segregated during mitosis. Considerable advances in
      parasite genetics and genomics have transformed apicomplexans, long considered
      hard to study, into highly tractable model organisms. We discuss how these
      resources might be marshalled to develop a detailed mechanistic picture of
      apicoplast cell biology.

PMID- 16968221
TI  - Structure and reactivity of Trypanosoma brucei pteridine reductase: inhibition by
      the archetypal antifolate methotrexate.
AB  - The protozoan Trypanosoma brucei has a functional pteridine reductase (TbPTR1),
      an NADPH-dependent short-chain reductase that participates in the salvage of
      pterins, which are essential for parasite growth. PTR1 displays broad-spectrum
      activity with pterins and folates, provides a metabolic bypass for inhibition of
      the trypanosomatid dihydrofolate reductase and therefore compromises the use of
      antifolates for treatment of trypanosomiasis. Catalytic properties of recombinant
      TbPTR1 and inhibition by the archetypal antifolate methotrexate have been
      characterized and the crystal structure of the ternary complex with cofactor
      NADP+ and the inhibitor determined at 2.2 A resolution. This enzyme shares 50%
      amino acid sequence identity with Leishmania major PTR1 (LmPTR1) and comparisons
      show that the architecture of the cofactor binding site, and the catalytic centre
      are highly conserved, as are most interactions with the inhibitor. However,
      specific amino acid differences, in particular the placement of Trp221 at the
      side of the active site, and adjustment of the beta6-alpha6 loop and alpha6 helix
      at one side of the substrate-binding cleft significantly reduce the size of the
      substrate binding site of TbPTR1 and alter the chemical properties compared with
      LmPTR1. A reactive Cys168, within the active site cleft, in conjunction with the
      C-terminus carboxyl group and His267 of a partner subunit forms a triad similar
      to the catalytic component of cysteine proteases. TbPTR1 therefore offers novel
      structural features to exploit in the search for inhibitors of therapeutic value
      against African trypanosomiasis.

PMID- 16968222
TI  - Eukaryotic cyclophilin as a molecular switch for effector activation.
AB  - Gram-negative phytopathogenic bacteria, such as Pseudomonas syringae, deliver
      multiple effector proteins into plant cells during infection. It is hypothesized
      that certain plant and mammalian effector proteins need to traverse the type III
      secretion system unfolded and are delivered into host cells as inactive enzymes.
      We have previously identified cyclophilin as the Arabidopsis eukaryotic activator
      of AvrRpt2, a P. syringae effector that is a cysteine protease. Cyclophilins are
      general folding catalysts and possess peptidyl-prolyl cis/trans isomerase
      (PPIase) activity. In this paper, we demonstrate the mechanism of AvrRpt2
      activation by the Arabidopsis cyclophilin ROC1. ROC1 mutants lacking PPIase
      enzymatic activity were unable to activate AvrRpt2. Furthermore, nuclear magnetic
      resonance spectroscopy revealed a structural change in AvrRpt2 from an unfolded
      to a folded state in the presence of ROC1. Using in vitro binding assays, ROC1's
      consensus binding sequence was identified as GPxL, a motif present at four sites
      within AvrRpt2. The GPxL motifs are located in close proximity to AvrRpt2's
      catalytic triad and are required for protease activity both in vitro and in
      planta. These data suggest that after delivery into the plant cell during
      infection, cyclophilin binds AvrRpt2 at four sites and properly folds the
      effector protein by peptidyl-prolyl cis/trans isomerization.

PMID- 16968223
TI  - Attenuation of penicillin resistance in a peptidoglycan O-acetyl transferase
      mutant of Streptococcus pneumoniae.
AB  - The level of penicillin resistance in clinical isolates of Streptococcus
      pneumoniae depends not only on the reduced affinity of penicillin binding
      proteins (PBPs) but also on the functioning of enzymes that modify the stem
      peptide structure of cell wall precursors. We used mariner mutagenesis in search
      of additional genetic determinants that may further attenuate the level of
      penicillin resistance in the bacteria. A mariner mutant of the highly penicillin
      resistant S. pneumoniae strain Pen6 showed reduction of the penicillin minimum
      inhibitory concentration (MIC) from 6 to 0.75 microg ml(-1). Decrease in
      penicillin MIC was also observed upon introduction of the mutation (named
      provisionally adr, for attenuator of drug resistance) into representatives of
      major epidemic clones of penicillin-resistant pneumococci. Attenuation of
      resistance levels was specific for beta-lactams. The adr mutant has retained
      unchanged (low affinity) PBPs, unaltered murM gene and unchanged cell wall stem
      peptide composition, but the mutant became hypersensitive to exogenous lysozyme
      and complementation experiments showed that both phenotypes--reduced resistance
      and lysozyme sensitivity--were linked to the defective adr gene. DNA sequence
      comparison and chemical analysis of the cell wall identified adr as the
      structural gene of the pneumococcal peptidoglycan O-acetylase.

PMID- 16968224
TI  - A systematic genetic analysis in Neisseria meningitidis defines the Pil proteins
      required for assembly, functionality, stabilization and export of type IV pili.
AB  - Although type IV pili (Tfp) are among the commonest virulence factors in
      bacteria, their biogenesis by complex machineries of 12-15 proteins, and thereby
      their function remains poorly understood. Interestingly, some of these proteins
      were reported to merely antagonize the retraction of the fibres powered by PilT,
      because piliation could be restored in their absence by a mutation in the pilT
      gene. The recent identification of the 15 Pil proteins dedicated to Tfp
      biogenesis in Neisseria meningitidis offered us the unprecedented possibility to
      define their exact contribution in this process. We therefore systematically
      introduced a pilT mutation into the corresponding non-piliated mutants and
      characterized them for the rescue of Tfp and Tfp-mediated virulence phenotypes.
      We found that in addition to the pilin, the main constituent of Tfp, only six Pil
      proteins were required for the actual assembly of the fibres, because apparently
      normal fibres were restored in the remaining mutants. Restored fibres were
      surface-exposed, except in the pilQ/T mutant in which they were trapped in the
      periplasm, suggesting that the PilQ secretin was the sole Pil component necessary
      for their emergence on the surface. Importantly, although in most mutants the
      restored Tfp were not functional, the pilG/T and pilH/T mutants could form
      bacterial aggregates and adhere to human cells efficiently, suggesting that Tfp
      stabilization and functional maturation are two discrete steps. These findings
      have numerous implications for understanding Tfp biogenesis/function and provide
      a useful groundwork for the characterization of the precise function of each Pil
      protein in this process.

PMID- 16968225
TI  - Comparative proteomic analysis of two Entamoeba histolytica strains with
      different virulence phenotypes identifies peroxiredoxin as an important component
      of amoebic virulence.
AB  - Entamoeba histolytica is a protozoan intestinal parasite that causes amoebic
      colitis and amoebic liver abscess. To identify virulence factors of E.
      histolytica, we first defined the phenotypes of two E. histolytica strains, HM
      1:IMSS, the prototype virulent strain, and E. histolytica Rahman, a strain that
      was reportedly less virulent than HM-1:IMSS. We found that compared with HM
      1:IMSS, Rahman has a defect in erythrophagocytosis and the ability to cause
      amoebic colitis in human colonic xenografts. We used differential in-gel 2D
      electrophoresis to compare the proteome of Rahman and HM-1:IMSS, and identified
      six proteins that were differentially expressed above a fivefold level between
      the two organisms. These included two proteins with antioxidative properties
      (peroxiredoxin and superoxide dismutase), and three proteins of unknown function,
      grainin 1, grainin 2 and a protein containing a LIM-domain. Overexpression of
      peroxiredoxin in Rahman rendered the transgenic trophozoites more resistant to
      killing by H2O2 in vitro, and infection with Rahman trophozoites expressing
      higher levels of peroxiredoxin was associated with higher levels of intestinal
      inflammation in human colonic xenografts, and more severe disease based on
      histology. In contrast, higher levels of grainin appear to be associated with a
      reduced virulence phenotype, and E. histolytica HM-1:IMSS trophozoites infecting
      human intestinal xenografts show marked decreases in grainin expression. Our data
      indicate that there are definable molecular differences between Rahman and HM
      1:IMSS that may explain the phenotypic differences, and identify peroxiredoxin as
      an important component of virulence in amoebic colitis.

PMID- 16968226
TI  - Epigenetic mechanisms are involved in the control of Giardia lamblia antigenic
      variation.
AB  - Giardia lamblia, an intestinal dwelling protozoan parasite, undergoes surface
      antigenic variation where only one of an estimated 150 variant-specific surface
      proteins (VSPs) is expressed and present on the surface at any one time.
      Transcriptional switching between VSPs results in replacement of one VSP by
      another. The mechanisms that control antigenic variation are poorly understood
      and difficult to study because there are multiple copies of each VSP and strong
      similarity with other VSPs. In order to study transcriptional regulation of one
      specific vsp, a haemagglutinin (HA) epitope-tagged h7 was integrated into the G.
      lamblia GS genome. We show that HA-tagged H7 undergoes antigenic variation in the
      same manner as native H7, also present in the GS genome. Control of expression of
      both HA-tagged H7 and native H7 is independent of each other even though the
      genes and their surrounding 5' and 3' flanking sequences are virtually identical.
      Analysis of expressing and non-expressing clones revealed an absence of HA-tagged
      h7 gene rearrangements upon switching and acetylation of histone lysine residues
      within the 167 nucleotides 5' to the expressed HA-tagged h7 gene. Lack of vsp
      rearrangements and acetylation of expressed immediate upstream regions implicates
      involvement of epigenetic mechanisms in antigenic variation.

PMID- 16968227
TI  - Treatment of Chlamydia trachomatis with a small molecule inhibitor of the
      Yersinia type III secretion system disrupts progression of the chlamydial
      developmental cycle.
AB  - The obligate intracellular bacterium Chlamydia trachomatis possesses a biphasic
      developmental cycle that is manifested by differentiation of infectious,
      metabolically inert elementary bodies (EBs) to larger, metabolically active
      reticulate bodies (RBs). The cycle is completed by asynchronous differentiation
      of dividing RBs back to a population of dormant EBs that can initiate further
      rounds of infection upon lysis of the host cell. Chlamydiae express a type III
      secretion system (T3SS) that is presumably employed to establish and maintain the
      permissive intracellular niche by secretion of anti-host proteins. We hypothesize
      that T3SS activity is essential for chlamydial development and pathogenesis.
      However, the lack of a genetic system has confounded efforts to establish any
      role of the T3SS. We therefore employed the small molecule Yersinia T3SS
      inhibitor N'-(3,5-dibromo-2-hydroxybenzylidene)-4-nitrobenzohydrazide, designated
      compound 1 (C1), to examine the interdependence of the chlamydial T3SS and
      development. C1 treatment inhibited C. trachomatis but not T4SS-expressing
      Coxiella burnetii development in a dose-dependent manner. Although chlamydiae
      remained viable and metabolically active, they failed to divide significantly and
      RB to EB differentiation was inhibited. These effects occurred in the absence of
      host cell cytotoxicity and were reversible by washing out C1. We further
      demonstrate that secretion of T3S substrates is perturbed in C1-treated
      chlamydial cultures. We have therefore provided evidence that C1 can inhibit C.
      trachomatis development and T3SS activity and present a model in which
      progression of the C. trachomatis developmental cycle requires a fully functional
      T3SS.

PMID- 16968228
TI  - All three chaperonin genes in the archaeon Haloferax volcanii are individually
      dispensable.
AB  - The Hsp60 or chaperonin class of molecular chaperones is divided into two
      phylogenetic groups: group I, found in bacteria, mitochondria and chloroplasts,
      and group II, found in eukaryotic cytosol and archaea. Group I chaperonins are
      generally essential in bacteria, although when multiple copies are found one or
      more of these are dispensable. Eukaryotes contain eight genes for group II
      chaperonins, all of which are essential, and it has been shown that these
      proteins assemble into double-ring complexes with eightfold symmetry where all
      proteins occupy specific positions in the ring. In archaea, there are one, two or
      three genes for the group II chaperonins, but whether they are essential for
      growth is unknown. Here we describe a detailed genetic, structural and
      biochemical analysis of these proteins in the halophilic archaeon, Haloferax
      volcanii. This organism contains three genes for group II chaperonins, and we
      show that all are individually dispensable but at least one must be present for
      growth. Two of the three possible double mutants can be constructed, but only one
      of the three genes is capable of fully complementing the stress-dependent
      phenotypes that these double mutants show. The chaperonin complexes are made up
      of hetero-oligomers with eightfold symmetry, and the properties of the different
      combinations of subunits derived from the mutants are distinct. We conclude that,
      although they are more homologous to eukaryotic than prokaryotic chaperonins,
      archaeal chaperonins have some redundancy of function.

PMID- 16968229
TI  - The response regulator ResD modulates virulence gene expression in response to
      carbohydrates in Listeria monocytogenes.
AB  - Listeria monocytogenes is a versatile bacterial pathogen that is able to
      accommodate to diverse environmental and host conditions. Presently, we have
      identified a L. monocytogenes two-component response regulator, ResD that is
      required for the repression of virulence gene expression known to occur in the
      presence of easily fermentable carbohydrates not found inside host organisms.
      Structurally and functionally, ResD resembles the respiration regulator ResD in
      Bacillus subtilis as deletion of the L. monocytogenes resD reduces respiration
      and expression of cydA, encoding a subunit of cytochrome bd. The resD mutation
      also reduces expression of mptA encoding the EIIABman component of a
      mannose/glucose-specific PTS system, indicating that ResD controls sugar uptake.
      This notion was supported by the poor growth of resD mutant cells that was
      alleviated by excess of selected carbohydrates. Despite the growth deficient
      phenotype of the mutant in vitro the mutation did not affect intracellular
      multiplication in epithelial or macrophage cell lines. When examining virulence
      gene expression we observed traditional induction by charcoal in both mutant and
      wild-type cells whereas the repression observed in wild-type cells by fermentable
      carbohydrates did not occur in resD mutant cells. Thus, ResD is a central
      regulator of L. monocytogenes when present in the external environment.

PMID- 16968230
TI  - Secondary metabolic gene cluster silencing in Aspergillus nidulans.
AB  - In contrast to most primary metabolism genes, the genes involved in secondary
      metabolism and certain nutrient utilization pathways are clustered in fungi.
      Recently a nuclear protein, LaeA, was found to be required for the transcription
      of several secondary metabolite gene clusters in Aspergillus nidulans. Here we
      show that LaeA regulation does not extend to nutrient utilization or the spoC1
      sporulation clusters. One of the secondary metabolite clusters regulated by LaeA
      contains the positive regulatory (i.e. aflR) and biosynthetic genes required for
      biosynthesis of sterigmatocystin (ST), a carcinogenic toxin. Analysis of ST gene
      cluster expression indicates LaeA regulation of the cluster is location specific
      as transcription of genes bordering the ST cluster are unaffected in a DeltalaeA
      mutant and placement of a primary metabolic gene, argB, in the ST cluster
      resulted in argB silencing in the DeltalaeA background. ST cluster gene
      expression was remediated when an additional copy of aflR was placed outside of
      the cluster but not when placed in the cluster. Site-specific mutation of an s
      adenosyl methionine (AdoMet) binding site in LaeA generated a DeltalaeA phenotype
      suggesting the protein to be a methyltransferase.

PMID- 16968231
TI  - Extensive phage dynamics in Staphylococcus aureus contributes to adaptation to
      the human host during infection.
AB  - Bacteriophages serve as a driving force in microbial evolution, adaptation to new
      environments and the pathogenesis of human bacterial infections. In
      Staphylococcus aureus phages encoding immune evasion molecules (SAK, SCIN,
      CHIPS), which integrate specifically into the beta-haemolysin (Hlb) gene, are
      widely distributed. When comparing S. aureus strain collections from infectious
      and colonizing situations we could detect a translocation of sak-encoding phages
      to atypical genomic integration sites in the bacterium only in the disease
      related isolates. Additionally, significantly more Hlb producing strains were
      detected in the infectious strain collection. Extensive phage dynamics
      (intragenomic translocation, duplication, transfer between hosts, recombination
      events) during infection was shown by analysing cocolonizing and consecutive
      isolates of patients. This activity leads to the splitting of the strain
      population into various subfractions exhibiting different virulence potentials
      (Hlb-production and/or production of immune evasion molecules). Thus, phage
      inducing conditions and strong selection for survival of the bacterial host after
      phage movement are typical for the infectious situation. Further in vitro
      characterization of phages revealed that: (i) SAK is encoded not only on
      serogroup F phages showing a conserved tropism for hlb but also on serogroup B
      phages which always integrate in a distinct intergenic region, (ii) the level of
      sak transcription correlates to phage inducibility but is independent of the
      phage localization in the chromosome, and (iii) phages can be stabilized extra
      chromosomally during their life cycle.

PMID- 16968232
TI  - Classification of odontogenic tumours. A historical review.
AB  - Using the term odontome for any tumour arising from the dental formative tissues,
      Broca suggested a classification of odontogenic tumours (OTs) in 1869. From 1888
      to 1914, Bland-Sutton and Gabell, James and Payne modified tumour terminology,
      while maintaining Broca's odontome concept. Thoma and Goldman's classification
      (1946) divided the OTs into tumours of ectodermal, mesodermal and mixed origin
      and abolished the general term odontome. The Pindborg and Clausen classification
      (1958) based on the idea that the reciprocal epithelial-mesenchymal tissue
      interactions were also operating in the pathogenesis of OTs. In 1966, WHO
      established a Collaborating Centre for the Histological Classification of
      Odontogenic Tumours and Allied Lesions (including jaw cysts) headed by Dr Jens
      Pindborg. In 1971, the first authoritative WHO guide to the classification of OTs
      and cysts appeared followed in 1992 by a second edition. In 2002, Philipsen and
      Reichart produced a revision of the 1992-edition and in 2003, the editors of the
      WHO Blue Book series: 'WHO Classification of Tumours' decided to produce a volume
      on the Head and Neck Tumours including a chapter on Odontogenic Tumours and Bone
      Related Lesions. In July of 2005 this volume was published by IARC, Lyon.

PMID- 16968233
TI  - Matrix metalloproteinase-7, -8, -9, -25, and -26 and CD43, -45, and -68 cell
      markers in HIV-infected patients' saliva and gingival tissue.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) process the extracellular matrix and
      act in tissue remodelling in many physiological and pathological conditions.
      Certain MMPs can also exert protective anti-inflammatory properties. The levels
      and expression of MMPs and tissue inhibitors of MMPs (TIMPs) in saliva and
      gingival tissues of human immunodeficiency virus-seropositive (HIV+) patients are
      unclear. METHODS: Enzyme-linked immunosorbent assay methods and Western blots
      were used to study levels and molecular forms of MMP-7, -8, -9, -25, and -26 and
      TIMP-1 from salivary samples of HIV+ patients (n = 55) and healthy controls (n =
      10). The expression of MMPs was also studied by immunohistochemical means in
      gingival tissue specimens (n = 11, HIV+ patients; n = 10, healthy controls).
      RESULTS: The HIV+ patients' MMP-8 levels in saliva were statistically
      significantly higher only in the acquired immunodeficiency syndrome (AIDS)-phase.
      MMP-9 levels in ASX- and AIDS-phases showed increased expression. TIMP-1 levels
      were significantly decreased in lymphadenopathy syndrome (LAS)- and AIDS-related
      complex (ARC)-phases, while MMP-8/TIMP-1 and MMP-9/TIMP-1 molar ratios were
      increased in all phases in comparison with controls. The molecular forms of MMP
      7, -25, and -26 were different between patients and controls as assessed by
      Western blot. Immunohistochemical studies showed slightly enhanced MMP-7, -8, -9,
      -25, and -26 staining in HIV+ gingival tissue samples in comparison with
      controls. CONCLUSIONS: This study confirmed and further demonstrated differences
      in salivary amounts and molecular forms of MMPs and TIMP-1 in HIV+ patients. The
      results may reflect alterations in host defence reactions associated with HIV
      infection.

PMID- 16968234
TI  - Effect of oral iron supplementation on unstimulated salivary flow rate: a
      randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: No treatment is known to permanently increase salivary flow in
      patients with hyposalivation. The objective of this study was to investigate the
      effect of iron supplementation on salivary flow rate. METHODS: A double-blind,
      randomized, placebo-controlled trial was carried out on 50 individuals with a low
      unstimulated whole salivary flow rate and low serum ferritin. Half the
      individuals received 60 mg iron orally twice a day for 3 months, while the other
      half received placebo. RESULTS: No statistically significant difference was found
      between the groups after treatment for the unstimulated flow rate and in the
      subjective assessments of oral dryness. The serum ferritin values increased
      significantly in the iron group but not in the placebo group. CONCLUSION: Oral
      supplementation with iron for 3 months has no effect on salivary flow rate among
      individuals with hyposalivation and low serum ferritin values.

PMID- 16968235
TI  - Oral shedding of herpes simplex virus type 1 in immunocompetent persons.
AB  - BACKGROUND: Reactivation of herpes simplex virus-1 (HSV-1) can result in
      recurrent herpes labialis lesions (RHL) and in oral shedding of virus. This study
      utilized polymerase chain reaction (PCR) to document the frequency and quantity
      of such shedding. METHODS: Thirty adults with greater than three RHL episodes per
      year were followed through one recurrence. They collected swabs for PCR every 12
      h starting at prodrome and for 10 days thereafter. Shedding was analyzed with
      regard to frequency, timing and quantity. RESULTS: HSV-1 was detectable in 87% of
      participants for a mean of 4 days. Shedding occurred most frequently during the
      vesicle/ulcer stage (91% of subjects), but was common in both clinical and
      subclinical stages (50% vs. 23%, average log DNA copy number/ml(2) 2.6 vs. 1.4).
      CONCLUSION: The majority of RHL patients shed viral DNA. Shedding occurred before
      and after the appearance of clinical lesions. Such findings may be useful in
      designing methods to reduce viral shedding and prevent transmission.

PMID- 16968236
TI  - Parameters of oxidative stress in saliva from diabetic and parenteral drug addict
      patients.
AB  - BACKGROUND: Oxidative stress constitutes the basis for many diseases and it may
      account for the severity of systemic and oral disease complications. The aim of
      this study was to assess whether saliva may be used to detect the body's
      oxidative stress level. METHODS: Oxidative stress was determined in saliva from
      14 diabetic patients and 10 heroin addicts; two different pathologic conditions
      related to free radical damage, and 21 healthy control subjects were included in
      the study. Glutathione peroxidase (GPx) and reductase (GRd) activities, and
      glutathione (GSH) and glutathione disulfide (GSSG) levels were analyzed in the
      saliva of all individuals. Other variables including salivary volume and the oral
      status were also analyzed. RESULTS: Diabetic patients had GPx and GRd activities
      of 39.98 +/- 1.61 and 6.19 +/- 0.61 nmol/min/mg prot, respectively. These values
      were significantly higher (P < 0.001) than those obtained in control saliva
      (27.51 +/- 0.86 and 3.44 +/- 0.25 nmol/min/mg prot, respectively). Drug addicts
      showed significantly (P < 0.001) lower salivary GPx and GRd activities than
      controls. Both group of patients had significantly lower levels of GSH and higher
      of GSSG than controls (P < 0.001). CONCLUSIONS: Changes in the antioxidant
      enzymes and glutathione levels in saliva from two different pathologic situations
      as those here studied suggest that this biologic fluid may be suitable for
      determining the prognosis and evolution of these diseases and its oral
      manifestations.

PMID- 16968237
TI  - Expression of complement restriction factors (CD46, CD55 & CD59) in head and neck
      squamous cell carcinomas.
AB  - BACKGROUND: Tumor cells can escape complement-dependent cytotoxicity (CDC) by
      expressing complement restriction factors (CRFs), CD46, CD55 and CD59. CRF
      expression in non-neoplastic mucosa of the head and neck was compared with
      biopsies of the head and neck squamous cell carcinoma (HNSCC) and cell lines
      derived from oral squamous cell carcinomas (OSCC). METHODS: Normal mucosa and
      HNSCC tumor tissue (poor, moderate, or well differentiated) specimens were
      immunostained with anti-CRF monoclonal antibodies. Immunostaining of the OSCC
      cell lines (SCC12 and SCC71) was examined under laser scan fluorescence
      microscopy. RESULTS: CD46, CD55 and CD59 were highly expressed in HNSCC cells
      including T1/T2N0M0 stages. The CRF expression was much lower or absent in non
      neoplastic squamous epithelia or in the submucosa of both normal and tumor
      tissues. CONCLUSIONS: Enhanced staining of tumor tissues at stages T1/T2
      indicates that the CRFs are overexpressed by primary tumors before metastasis to
      either lymph nodes or organs (N0M0 stage) suggesting that CRFs are formed early
      during tumorigenesis.

PMID- 16968238
TI  - Expression of p53, Ki-67, and EGFR in odontogenic keratocysts before and after
      decompression.
AB  - BACKGROUND: Sixteen odontogenic keratocysts were examined morphologically and
      immunohistochemically for changes in proliferative activity before and after
      decompression using p53, Ki-67, and expression of growth factor (EGFR). METHODS:
      p53 and Ki-67 positivity was scored by counting 500 cells and then counting the
      number of brown staining nuclei out of these. EGFR was scored using guidelines
      for scoring Herceptest [Dako (Her-2)]. A Wilcoxon test was performed on the
      results. RESULTS: The values of Ki-67 and p53 before and after decompression were
      without significant change. There was no significant change in EGFR expression
      either. No correlation was found between inflammation or decompression time and
      expression of EGFR, p53, and Ki-67. The degree of change of the epithelium was
      varying, yet the reduction of the cysts size was considerable (18-100%- average
      47.6%). CONCLUSION: The morphologic changes in the cysts could not be correlated
      with expression of Ki-67, p53 or EGFR, to the clinical reduction of the cysts or
      the time of decompression.

PMID- 16968239
TI  - Synchronous ameloblastoma and orthokeratinized odontogenic cyst of the mandible.
AB  - The simultaneous occurrence of ameloblastomas with odontogenic cysts or other non
      odontogenic lesions have already been described as combined lesions. However, we
      are unaware of any report in the English literature of simultaneous occurrence of
      ameloblastoma and orthokeratinized odontogenic cyst (OOC) occurring as completely
      distinct lesions. This report shows a case of synchronous ameloblastoma and OOC,
      located on posterior regions of the mandible, but in distinct sides.

PMID- 16968240
TI  - Epulis granulomatosa as an oral manifestation of Klippel-Trenaunay syndrome.
AB  - The Klippel-Trenaunay syndrome (KTS) was first described by Klippel and Trenaunay
      in 1900. It is characterized by the triad of hemihypertrophy of soft and hard
      tissue, naevus flammeus and venous varicosity in the affected area. Though all
      oral tissues may be affected, only 5% of KTS show manifestations in the head and
      neck region. Only three cases are described with an oral manifestation, showing
      gingival overgrowth clinically and histologically corresponding to a pyogenic
      granuloma. It is still uncertain whether the combination of gingival fibromatosis
      and KTS is significant or coincidental. We report about a 25-year-old patient
      with KTS and recidivous gingival fibromatosis, clinically and histologically
      corresponding to an epulis fibromatosa in a case report. It is suggested that
      this occurrence is significant.

PMID- 16968241
TI  - Mixed testicular germ cell tumor presenting as metastatic pure choriocarcinoma
      involving the maxillary gingiva.
AB  - Gingival metastases are infrequent and invariably associated with a widespread
      disease and a poor prognosis. Because of their unremarkable clinical appearance,
      they can be difficult to distinguish from more common gingival hyperplastic or
      reactive lesions, such as pyogenic granuloma, peripheral giant cell granuloma,
      and peripheral ossifying granuloma. We are reporting here an unusual case of a 36
      year-old man with a mixed testicular germ cell tumor presenting as a metastatic
      pure choriocarcinoma involving the maxillary gingiva, extending from the first
      left premolar to the left second maxillary molar, mimicking a 'benign looking'
      gingival mass. Gingival metastases may be the first manifestation of a widespread
      metastatic disease and therefore particular attention must be paid to gingival
      lesions associated with atypical clinical symptoms and/or signs.

PMID- 16968242
TI  - Mucinous adenocarcinoma of the temporal region initially diagnosed as
      temporomandibular disorders: a case report.
AB  - Adenocarcinoma occurring in the temporal region has not previously been reported.
      We present a case of mucinous adenocarcinoma of the temporal region. A 62-year
      old female patient was diagnosed as having temporomandibular disorders because of
      severe trismus and joint pain. Although trismus progressively worsened, there
      were no abnormal findings on diagnostic imaging studies including magnetic
      resonance imaging (MRI) and bone scintigraphy. As swelling of the temporal region
      was observed, biopsy was performed. Histologic examination showed chronic
      inflammation of the striated muscle. Approximately 6 months later, follow-up MRI
      demonstrated an ill-defined mass lesion in the infratemporal region extending to
      the intracranium. Histologic diagnosis of the biopsy showed that this mass lesion
      was moderately differentiated mucinous adenocarcinoma.

PMID- 16968244
TI  - Morphological examination of the intraorbital muscles (musculi bulbi) in dogs in
      the perinatal period.
AB  - Twelve American Staffordshire terriers, gestational day 60, and 10 dogs de
      Bordeaux, gestational day 57 were examined in respect of the morphology and
      morphometry of their intraorbital muscles. The location of the retractor bulbi,
      recti and oblique muscles was described and the length of the muscles, the length
      and breadth of their tendons as well as the distance of the distal insertions of
      the muscle tendons from the corneal limbus were measured. Similarly, the shape of
      the line of distal insertions was investigated. The measurements were taken with
      an electronic caliper to the nearest 0.1 mm. The distance insertion-corneal
      limbus was measured by means of the Hifny and Misk method (1982). The following
      differences between the breeds in the morphometry of the intraorbital muscles and
      their tendons were found out. The distal insertions of the tendons of the dorsal,
      ventral and lateral recti muscles are further from the corneal limbus in American
      Staffordshire terriers than in dogs de Bordeaux. The muscular funiculi of the
      retractor bulbi muscle are further from the corneal limbus in dogs de Bordeaux,
      except the dorsolateral funiculus (1.96/1.94 mm). In addition, there are
      differences in the morphometry of the intraorbital muscles and their tendons. No
      differences, however, were found in the morphology of the intraorbital muscle
      tendons (their insertion line) and their location. The study can be applied to
      clinical sciences (surgery) and veterinary ophthalmology, in particular.

PMID- 16968245
TI  - Canine spinal cord neuron and axon myelin sheath morphometry.
AB  - This inedited morphometric study has been developed from healthy canine spinal
      cord neuron cytoplasm and nucleus, and white matter axonal myelin sheath, from
      cervical, thoracic and lumbar regions. For the morphometric study, the parameters
      were area, perimeter, maximum and minimum diameters and roundness for neurons and
      myelin thickness for axon. For each parameter, 300 neurons were analysed. The
      results revealed that lumbar neurons had the highest mean values for the analysed
      parameters, indicating the presence of large neurons in this region, with large
      axons as a result of myelin thickness, which is proportional to axon calibre. We
      conclude that these morphometric results can contribute for the establishment of
      normal patterns, for canine spinal cord cervical, thoracic and lumbar segments.

PMID- 16968246
TI  - Intercellular junctions in rabbit eye ora serrata.
AB  - Summary The aim of this study was to describe and localize the intercellular
      junctions in the ora serrata region of albino and pigmented rabbit eyes. Eyes of
      albino and pigmented rabbits were fixed and processed for transmission electron
      microscopy. Light and electron microscope examination was carried out on semithin
      and ultrathin sections. The ora serrata region showed adherens, gap and tight
      junctions in the retinal and ciliary margins of albino and pigmented rabbit eyes.
      In the retinal margin, zonulae adherens between Muller cells and photoreceptors
      are associated with tight junctions. In the ciliary margin, epithelial cells are
      joined by adherens, gap and tight junctions localized between apical and
      apicolateral cell membranes. Tight junctions appear as zonulae occludens in the
      non-pigmented apicolateral cell membranes and as tight focal junctions between
      pigmented and non-pigmented apical cell membranes. Between the ciliary and
      retinal margins there are adherens and tight focal junctions which attach
      pigmented apical cell membranes to adjacent cells. There were no differences in
      the distribution of intercellular junctions between albino and pigmented rabbits.

PMID- 16968247
TI  - Quantification by image analysis of the Gallus gallus lung elastic fibres from
      embryonic to adult birds.
AB  - The organization of the lung's elastic fibres is amazingly uniform in all
      vertebrates, with the possible exception of birds, whose pulmonary architecture
      and air movement are unique. The overall goal of this work was to study and
      quantify elastic fibre distribution patterns and relative amounts in the
      parabronchi, during the incubation period until the 42nd day after hatching.
      Chick embryo lungs were examined on the 14th, 16th, 18th and 20th days of
      incubation and chick lungs on the 1st, 2nd, 7th, 14th, 35th and 42nd days after
      hatching. Four animals were used daily, and the observations were randomly
      performed on both lungs. A morphometric study was carried out focusing on the
      computerized image analysis of histological sections stained according to a
      modified Gomori technique. The values obtained for each day result from the
      observation and processing of 20 images. Complementary studies were performed
      using transmission electron microscopy, as on the 14th embryonic day the fibres
      were not visible on light microscopy. The results show that the area occupied by
      the elastic fibres increases gradually from the 16th day of incubation up till
      the 7th day after hatching and decreases slowly in the following days of the
      study. A prominent increase takes place before hatching, which points out to the
      adequate and essential structural roles played by the elastic fibres in the
      pulmonary maturation process.

PMID- 16968248
TI  - The oral cavity of the adult zebrafish (Danio rerio).
AB  - The zebrafish is a common model for developmental studies including those
      regarding tooth, palate and tongue. Nevertheless, little information is available
      about the morphology of the oral cavity in this teleost, especially in adult
      animals. In this study we used light, scanning and transmission electron
      microscopy to describe in detail the morphology of the oral cavity of adult
      zebrafish. The oral cavity could be divided into three different zones: the outer
      containing the lips, the intermediate corresponding to the internal valves and
      the internal that corresponds to the tongue. In the upper and lower intermediate
      zones, there were semilunar shaped valves, more prominent in the upper part. The
      internal lower zones correspond to the palate and the tongue, which is an
      individualized structure filled with numerous transversal ridges. Both the
      intermediate and internal zones were covered by a stratified epithelium
      containing numerous mucous and rodlet cells. Present data provide the first
      description of the morphology and structure of the oral cavity in the adult
      zebrafish and might serve as a baseline for developmental studies of the oral
      cavity using this teleost as a model.

PMID- 16968249
TI  - Immunohistochemical localization of insulin-like growth factor-I receptor (IGF
      IR) in the developing and mature rat testes.
AB  - It has been suggested that insulin-like growth factor-I (IGF-I) plays an
      important role in the regulation of spermatogenesis in the testes. Its signal is
      mediated predominantly by the IGF-I receptor (IGF-IR). Signalling through IGF-IR
      has been shown to have a potent survival function. IGF-IR, a transmembrane
      tyrosine kinase, is widely expressed across many cell types. In this study, we
      demonstrated the distribution of IGF-IR in testes of differently aged rats. Anti
      IGF-IR is a rabbit polyclonal antibody raised against a peptide mapping at the
      carboxy terminus of the IGF-IR of human origin. Testicular specimens were fixed
      in Bouin's solution and embedded in paraffin. The paraffin-embedded sections were
      processed for standard immunohistochemistry by the labelled streptavidin-biotin
      technique. At postnatal day 19, IGF-IR immunoreactivity was seen moderately in
      spermatogonia, and slightly both in leptotene and zygotene primary spermatocytes.
      At postnatal day 35, immunoreactivity was seen slightly both in the pachytene
      primary spermatocytes and Leydig cells. Although there was intense
      immunoreactivity in the Leydig cells and in the elongated spermatids on days 50
      and 70, the intensity of reaction was decreased in the elongated spermatids in
      the 10th month. Our results suggest that IGF-IR may play significant roles in
      testicular function and germ cell development.

PMID- 16968250
TI  - Comparative study of compact bone tissue microstructure between non-transgenic
      and transgenic rabbits with WAP-hFVIII gene construct.
AB  - The aim of this study was to investigate differences in compact bone tissue
      microstructure between New Zealand White transgenic rabbits with human blood
      clotting factor VIII gene and the non-transgenic ones. The transgene was under
      the transcriptional control of the whey acidic protein (WAP) promoter.
      Altogether, 42 femora were analysed. Specimens were prepared using standard
      histological equipment, producing thin sections approximately 80-100 microm.
      Areas, perimeters, minimum and maximum diameters of vascular canals of primary
      osteons, Haversian canals and secondary osteons were measured. Our results
      indicate the basic structural pattern of the bone tissue was primary vascular
      longitudinal in both groups of rabbits. However, a fibrolamellar bone tissue was
      identified only in the transgenic rabbits. The measured variables of the vascular
      canals of the primary osteons, the Haversian canals and the secondary osteons
      were higher in transgenic rabbits in comparison with non-transgenic ones in most
      cases and the differences were often statistically significant (P < 0.01; P <
      0.001). More significant differences were noticed in males (transgenic versus non
      transgenic). However, it is not easy to find the real cause of the changes.
      Despite the fact that no hFVIII mRNA expression was found in the analysed bone of
      transgenic rabbits, we presume that the observed differences could be associated
      with transgenesis. In this article, we discuss possible associations between
      transgene integration as well as aneuploidy and/or observed microstructural
      changes in compact bone tissue.

PMID- 16968251
TI  - Anatomoradiographic description of the teeth of pacas bred in captivity (Agouti
      paca, Linnaeus, 1766).
AB  - Two newborn males, two adult males 9 and 72 months old, one newborn female and
      two adult females of 30 and 54 months old pacas were used. Animals were
      radiographed on lateral recumbency, teeth were extracted and the vestibulolingual
      and mesiodistal lengths were achieved at the occlusal surface, besides the
      longitudinal length. The lower incisors presented greater length in relation to
      the other ones and sinuous shape; the upper incisors, relatively smaller, are
      practically straight. There is no canine tooth, and after a great diastema there
      is one premolar and three molars in each hemiarcade. In adult pacas, the enamel
      of incisors presents yellowish colour, mainly in the labial surface; in the
      premolars and molars, the enamel is present as internal sheets disposed nearly in
      a parallel way and in vestibulolingual direction, through practically all the
      dental length, which provides several joined teeth aspect.

PMID- 16968252
TI  - Ancient pompeian dogs--morphological and morphometric evidence for different
      canine populations.
AB  - This article examines the morphological features of the dog during the Roman Age
      on the basis of osseous and dental remains dug up in Pompeii. The material,
      consisting of 113 canine bones and teeth, was subjected to both morphological and
      morphometrical analyses and was compared with modern canine breeds. In most
      cases, the age at death, shoulder height and other phenotypic features were
      ascertained. The examined Pompeian canine population fell mainly into two
      categories: small- and large-sized animals. Among the former, one brachycephalic
      and two dolichocephalic subjects were included. Such morphological features agree
      with what is described in numerous texts and appears in mosaics, bas-reliefs and
      frescoes of the Roman Age. As small-sized dogs cannot be classified as Canes
      Venatici (sporting dogs), Canes Villatici (watch dogs) and Canes Pastorales
      (shepherd dogs) according to Columella's De re rustica, these animals may be
      considered as lapdogs.

PMID- 16968253
TI  - Morphology of the intermandibular gland of the Lesser mouse deer, Tragulus
      javanicus.
AB  - The morphology of the intermandibular gland of the Lesser mouse deer (Tragulus
      javanicus), which plays an important function in marking area and territory and
      in the reproductive behaviour of the animal, was examined using
      immunohistochemistry, lectin histochemistry and scanning electron microscopy. The
      gland was composed of sebaceous and apocrine glandular material. Sebaceous glands
      occupied a greater area of the total gland and consisted of many large lobules
      with polyhedral cells having a pale cytoplasm. The sebaceous gland, being
      holocrine, possessed no special secretory ducts. The apocrine gland was lined by
      cuboid cells and the secretory products were often seen in the apical portions of
      the cells. Myoepithelial cells contained actin filaments lining the basal
      membranes of the apocrine gland and were surrounded by nerve fibres which
      immunostained with protein gene product 9.5. The secretion of the gland appears
      to be a mixture of larger amounts of lipid material from sebaceous glands, and
      glycoconjugates secreted by both sebaceous and apocrine glands. Lectin
      histochemistry detected these as galactose, N-acetyl-D-galactosamine, N-acetyl-D
      glucosamine, D-mannose and D-glucose. The male gland was larger in size and
      contained more N-acetyl galactosamine and N-acetyl glucosamine in its secretion
      than the gland of the female. This implied the presence of sexual differences in
      secretions in the intermandibular gland of the Lesser mouse deer.

PMID- 16968254
TI  - Localization of oestrogen receptors within various bovine ovarian cell types at
      different stages of the oestrous cycle.
AB  - In the present study oestrogen receptor alpha(ERalpha) and oestrogen receptor
      beta (ERbeta) mRNA were localized in various ovarian cell types of 23 cows at
      different stages of the oestrous cycle. ERalpha was detected by
      immunohistochemistry and the localization of ERbeta mRNA was examined using in
      situ hybridization. The immunostaining of ERalpha was low in the ovarian
      follicles, tunica albuginea and surface epithelium, but high in cells of the deep
      stroma and superficial stroma, which indicates a functional role of ERalpha in
      the cells surrounding the follicles. In contrast, ERbeta mRNA scores were low to
      moderate in primordial and primary follicles, and increased with the development
      of the follicle. ERbeta mRNA scores were higher in cystic follicles than in
      obliterative follicles. In the corpora lutea and corpora albicantia the scores
      for ERbeta mRNA were moderate. Furthermore, in the corpora lutea, ERbeta mRNA
      levels showed cyclic variations and were low during early dioestrus. The
      correlation between plasma progesterone levels and the score for ER was low and
      negative in all ovarian cell types. This study demonstrates the predominant role
      of ERbeta over ERalpha in bovine ovarian structures. Furthermore, the
      colocalization of both ERbeta mRNA and ERalpha in most cell types suggests
      possible interactions between both ER subtypes.

PMID- 16968255
TI  - Mammary gland secretory concretions contain non-collagenous bone matrix proteins.
AB  - Secretory concretions in mammary gland alveoli are commonly of microscopical
      size. However, some concretions reach clinically palpable dimensions and may
      occlude teat canals and obstruct milk flow. We studied secretory concretions in
      sheep, goat and cow mammary glands, using routine histological staining methods,
      conventional histochemistry and electron microscopy. As concretions frequently
      mineralize, immunostaining for keratan sulphate and calcium-binding non
      collagenous bone matrix proteins (bone sialoprotein, osteocalcin, osteonectin and
      osteopontin) was performed. Concretions consisted of organic matrix (condensed
      secretions) with calcium precipitates. Mineralized deposits mostly show
      concentric organization, bound haematoxylin, and were readily identified in H&E
      stained sections. Mineral components of concretions reacted for calcium carbonate
      and phosphate, organic matrix was found to contain sialoglycan material.
      Immunohistochemistry revealed bone sialoprotein, osteonectin and keratan sulphate
      in cow and goat concretions. Osteocalcin was detected in sheep, cow and goat
      concretions, whilst osteopontin was not identified in any of the specimens
      studied. Our results indicate the presence of non-collagenous bone matrix
      proteins (except osteopontin) in mammary gland concretions. These glycoproteins
      are commonly thought to govern mineralization of organic matrix and are assumed
      also to promote mineral deposition in mammary gland secretory concretions.
      Besides caseins, these particular glycoproteins have to be considered as calcium
      binding milk proteins.

PMID- 16968257
TI  - Molecular marker systems in insects: current trends and future avenues.
AB  - Insects comprise the largest species composition in the entire animal kingdom and
      possess a vast undiscovered genetic diversity and gene pool that can be better
      explored using molecular marker techniques. Current trends of application of DNA
      marker techniques in diverse domains of insect ecological studies show that
      mitochondrial DNA (mtDNA), microsatellites, random amplified polymorphic DNA
      (RAPD), expressed sequence tags (EST) and amplified fragment length polymorphism
      (AFLP) markers have contributed significantly for progresses towards
      understanding genetic basis of insect diversity and for mapping medically and
      agriculturally important genes and quantitative trait loci in insect pests. Apart
      from these popular marker systems, other novel approaches including transposon
      display, sequence-specific amplification polymorphism (S-SAP), repeat-associated
      polymerase chain reaction (PCR) markers have been identified as alternate marker
      systems in insect studies. Besides, whole genome microarray and single nucleotide
      polymorphism (SNP) assays are becoming more popular to screen genome-wide
      polymorphisms in fast and cost effective manner. However, use of such
      methodologies has not gained widespread popularity in entomological studies. The
      current study highlights the recent trends of applications of molecular markers
      in insect studies and explores the technological advancements in molecular marker
      tools and modern high throughput genotyping methodologies that may be applied in
      entomological researches for better understanding of insect ecology at molecular
      level.

PMID- 16968258
TI  - Nuclear and mitochondrial markers reveal distinctiveness of a small population of
      bottlenose whales (Hyperoodon ampullatus) in the western North Atlantic.
AB  - Small populations at the edge of a species' distribution can represent
      evolutionary relics left behind after range contractions due to climate change or
      human exploitation. The distinctiveness and genetic diversity of a small
      population of bottlenose whales in the Gully, a submarine canyon off Nova Scotia,
      was quantified by comparison to other North Atlantic populations using 10
      microsatellites and mitrochondrial DNA (mtDNA) control region sequences (434 bp).
      Both markers confirmed the distinctiveness of the Gully (n = 34) from the next
      nearest population, off Labrador (n = 127; microsatellites -F(ST)= 0.0243, P <
      0.0001; mtDNA -Phi(ST) = 0.0456, P < 0.05). Maximum likelihood microsatellite
      estimates suggest that less than two individuals per generation move between
      these areas, refuting the hypothesis of population links through seasonal
      migration. Both males and females appear to be philopatric, based on significant
      differentiation at both genomes and similar levels of structuring among the sexes
      for microsatellites. mtDNA diversity was very low in all populations (h = 0.51,
      pi = 0.14%), a pattern which may be due to selective sweeps associated with this
      species' extreme deep-diving ecology. Whaling had a substantial impact on
      bottlenose whale abundance, with over 65 000 animals killed before the hunt
      ceased in the early 1970s. Genetic diversity was similar among all populations,
      however, and no signal for bottlenecks was detected, suggesting that the Gully is
      not a relic of a historically wider distribution. Instead, this unique ecosystem
      appears to have long provided a stable year-round habitat for a distinct
      population of bottlenose whales.

PMID- 16968259
TI  - Presumptive horizontal symbiont transmission in the fungus-growing termite
      Macrotermes natalensis.
AB  - All colonies of the fungus-growing termite Macrotermes natalensis studied so far
      are associated with a single genetically variable lineage of Termitomyces
      symbionts. Such limited genetic variation of symbionts and the absence of sexual
      fruiting bodies (mushrooms) on M. natalensis mounds would be compatible with
      clonal vertical transmission, as is known to occur in Macrotermes bellicosus. We
      investigated this hypothesis by analysing DNA sequence polymorphisms as
      codominant SNP markers of four single-copy gene fragments of Termitomyces
      isolates from 31 colonies of M. natalensis. A signature of free recombination was
      found, indicative of frequent sexual horizontal transmission. First, all 31
      strains had unique multilocus genotypes. Second, SNP markers (n = 55) were
      largely in Hardy-Weinberg equilibrium (90.9%) and almost all possible pairs of
      SNPs between genetically unlinked loci were in linkage equilibrium (96.7%).
      Finally, extensive intragenic recombination was found, especially in the EF1alpha
      fragment. Substantial genetic variation and a freely recombining population
      structure can only be explained by frequent horizontal and sexual transmission of
      Termitomyces. The apparent variation in symbiont transmission mode among
      Macrotermes species implies that vertical symbiont transmission can evolve
      rapidly. The unexpected finding of horizontal transmission makes the apparent
      absence of Termitomyces mushrooms on M. natalensis mounds puzzling. To our
      knowledge, this is the first detailed study of the genetic population structure
      of a single lineage of Termitomyces.

PMID- 16968260
TI  - Fine-scale genetic structure and dispersal in cooperatively breeding
      apostlebirds.
AB  - In cooperatively breeding species, restricted dispersal of offspring leads to
      clustering of closely related individuals, increasing the potential both for
      indirect genetic benefits and inbreeding costs. In apostlebirds (Struthidea
      cinerea), philopatry by both sexes results in the formation of large (up to 17
      birds), predominantly sedentary breeding groups that remain stable throughout the
      year. We examined patterns of relatedness and fine-scale genetic structure within
      a population of apostlebirds using six polymorphic microsatellite loci. We found
      evidence of fine-scale genetic structure within the study population that is
      consistent with behavioural observations of short-distance dispersal, natal
      philopatry by both sexes and restricted movement of breeding groups between
      seasons. Global F(ST) values among breeding groups were significantly positive,
      and the average level of pairwise relatedness was significantly higher for
      individuals within groups than between groups. For individuals from different
      breeding groups, geographical distance was negatively correlated with pairwise
      relatedness and positively correlated with pairwise F(ST). However, when each sex
      was examined separately, this pattern was significant only among males,
      suggesting that females may disperse over longer distances. We discuss the
      potential for kin selection to influence the evolution and maintenance of
      cooperative breeding in apostlebirds. Our results demonstrate that spatial
      genetic structural analysis offers a useful alternative to field observations in
      examining dispersal patterns of cooperative breeders.

PMID- 16968261
TI  - Divergence in mating signals correlates with ecological variation in the
      migratory songbird, Swainson's thrush (Catharus ustulatus).
AB  - Song divergence among populations of passerine birds is recognized as a
      potentially important premating isolation mechanism and may represent the first
      step in speciation. Because song divergence may be influenced by an array of
      acoustic, ecological, and genetic factors, the study of its origin requires a
      multifaceted approach. Here we describe the relationship between acoustic,
      neutral genetic and ecological variation in five populations of the Swainson's
      thrush: two from coastal temperate rainforest habitat representing the 'russet
      backed' subspecies group, two from inland coniferous forest habitat representing
      the 'olive-backed' subspecies group, and one mixed locality that resides within a
      contact zone between the two groups. Song in the five populations is analysed
      using a multivariate analysis of spectral and temporal measurements, population
      genetic structure is assessed using an analysis of five microsatellite loci and
      ecological differences between populations are quantified using an analysis of
      climatic parameters. Matrix correspondence tests are used to distinguish between
      the potential for drift and selection in driving song divergence. No significant
      correlation was found between acoustic and genetic distance suggesting that song
      divergence cannot be explained by drift alone. A significant correlation between
      ecological and acoustic distance after accounting for genetic distance, suggests
      a potential role for ecological selection on divergence in spectral and temporal
      components of Swainson's thrush song.

PMID- 16968262
TI  - An empirical verification of population assignment methods by marking and
      parentage data: hatchery and wild steelhead (Oncorhynchus mykiss) in Forks Creek,
      Washington, USA.
AB  - Assignment tests are increasingly applied in ecology and conservation, although
      empirical comparisons of methods are still rare or are restricted to few of the
      available approaches. Furthermore, the performance of assignment tests in cases
      with low population differentiation, violations of Hardy-Weinberg equilibrium and
      unbalanced sampling designs has not been verified. The release of adult hatchery
      steelhead to spawn in Forks Creek in 1996 and 1997 provided an opportunity to
      compare the power of different assignment methods to distinguish their offspring
      from those of sympatric wild steelhead. We compared standard assignment methods
      requiring baseline samples (frequency, distance and Bayesian) and clustering
      approaches with and without baseline information, using six freely available
      computer programs. Assignments were verified by parentage data obtained for a
      subset of returning offspring. All methods provided similar assignment success,
      despite low differentiation between wild and hatchery fish (F(ST) = 0.02).
      Bayesian approaches with baseline data performed best, whereas the results of
      clustering methods were variable and depended on the samples included in the
      analysis and the availability of baseline information. Removal of a locus with
      null alleles and equalizing sample sizes had little effect on assignments. Our
      results demonstrate the robustness of most assignment tests to low
      differentiation and violations of assumptions, as well as their utility for
      ecological studies that require correct classification of different groups.

PMID- 16968263
TI  - Decomposed pairwise regression analysis of genetic and geographic distances
      reveals a metapopulation structure of stream-dwelling Dolly Varden charr.
AB  - Isolation by distance is usually tested by the correlation of genetic and
      geographic distances separating all pairwise populations' combinations. However,
      this method can be significantly biased by only a few highly diverged populations
      and lose the information of individual population. To detect outlier populations
      and investigate the relative strengths of gene flow and genetic drift for each
      population, we propose a decomposed pairwise regression analysis. This analysis
      was applied to the well-described one-dimensional stepping-stone system of stream
      dwelling Dolly Varden charr (Salvelinus malma). When genetic and geographic
      distances were plotted for all pairs of 17 tributary populations, the correlation
      was significant but weak (r(2) = 0.184). Seven outlier populations were
      determined based on the systematic bias of the regression residuals, followed by
      Akaike's information criteria. The best model, 10 populations included, showed a
      strong pattern of isolation by distance (r(2) = 0.758), suggesting equilibrium
      between gene flow and genetic drift in these populations. Each outlier population
      was also analysed by plotting pairwise genetic and geographic distances against
      the 10 nonoutlier populations, and categorized into one of the three patterns:
      strong genetic drift, genetic drift with a limited gene flow and a high level of
      gene flow. These classifications were generally consistent with a priori
      predictions for each population (physical barrier, population size, anthropogenic
      impacts). Combined the genetic analysis with field observations, Dolly Varden in
      this river appeared to form a mainland-island or source-sink metapopulation
      structure. The generality of the method will merit many types of spatial genetic
      analyses.

PMID- 16968264
TI  - Genetic structure and assignment tests demonstrate illegal translocation of red
      deer (Cervus elaphus) into a continuous population.
AB  - Molecular forensic methods are being increasingly used to help enforce wildlife
      conservation laws. Using multilocus genotyping, illegal translocation of an
      animal can be demonstrated by excluding all potential source populations as an
      individual's population of origin. Here, we illustrate how this approach can be
      applied to a large continuous population by defining the population genetic
      structure and excluding suspect animals from each identified cluster. We aimed to
      test the hypothesis that recreational hunters had illegally introduced a group of
      red deer into a hunting area in Luxembourg. Reference samples were collected over
      a large area in order to test the possibility that the suspect individuals might
      be recent immigrants. Due to isolation-by-distance relationships in the data set,
      inferring the number of genetic clusters using Bayesian methods was not
      straightforward. Biologically meaningful clusters were only obtained by
      simultaneously analysing spatial and genetic information using the program baps
      4.1. We inferred the presence of three genetic clusters in the study region.
      Using partial Mantel tests, we detected barriers to gene flow other than
      distance, probably created by a combination of urban areas, motorways and a river
      valley used for viticulture. The four focal animals could be excluded with a high
      certainty from the three genetic subpopulations and it was therefore likely that
      they had been released illegally.

PMID- 16968265
TI  - Demographic spatial genetic structure of the Neotropical tree, Jacaranda copaia.
AB  - We used genotypes from six microsatellite loci and demographic data from a large
      mapped forest plot to study changes in spatial genetic structure across
      demographic stages, from seed rain to seedlings, juveniles, and adult diameter
      classes in the Neotropical tree, Jacaranda copaia. In pairwise comparisons of
      genetic differentiation among demographic classes, only seedlings were
      significantly differentiated from the other diameter classes; F(ST) values ranged
      from 0.006 to 0.009. Furthermore, only seedlings showed homozygote excess
      suggesting biparental inbreeding in the large diameter reproductive adults. We
      found very low levels of relatedness in the first distance class of trees, 1-26
      cm diameter (F(ij) = 0.011). However, there was a 5- to 10-fold rise in
      relatedness in the smallest distance class, from the smallest to the largest tree
      diameter classes (F(ij) = 0.110 for individuals > 56 cm diameter). A variety of
      non-mutually exclusive mechanisms have been invoked perviously to explain such a
      pattern, including natural selection, history, or nonequilibrium population
      dynamics. The long-term demographic data available for this species allow us to
      evaluate these mechanisms. Jacaranda is a fast-growing, light-demanding species
      with low recruitment rates and high mortality rates in the smaller diameter
      classes. It successfully regenerates only in large light gaps, which occur
      infrequently and stochastically in space and time. These factors contribute to
      the nonequilibrium population dynamics and observed low genetic structure in the
      small size classes. We conclude that the pattern of spatial genetic transitions
      in Jacaranda is consistent with overlapping related generations and strong but
      infrequent periods of high recruitment, followed by long periods of population
      decline.

PMID- 16968266
TI  - Evidence of microsatellite hitch-hiking selection in Atlantic cod (Gadus morhua
      L.): implications for inferring population structure in nonmodel organisms.
AB  - Microsatellites have gained wide application for elucidating population structure
      in nonmodel organisms. Since they are generally noncoding, neutrality is assumed
      but rarely tested. In Atlantic cod (Gadus morhua L.), microsatellite studies have
      revealed highly heterogeneous estimates of genetic differentiation among loci. In
      particular one locus, Gmo 132, has demonstrated elevated genetic differentiation.
      We investigated possible hitch-hiking selection at this and other microsatellite
      loci in Atlantic cod. We employed 11 loci for analysing samples from the Baltic
      Sea, North Sea, Barents Sea and Newfoundland covering a large part of the
      species' distributional range. The 'classical' Lewontin-Krakauer test for
      selection based on variance in estimates of F(ST) and (standardized genetic
      differentiation) revealed only one significant pairwise test (North Sea-Barents
      Sea), and the source of the elevated variance could not be ascribed exclusively
      to Gmo 132. In contrast, different variants of the recently developed ln Rtheta
      test for selective sweeps at microsatellite loci revealed a high number of
      significant outcomes of pair-wise tests for Gmo 132. Further, the presence of
      selection was indicated in at least one other locus. The results suggest that
      many previous estimates of genetic differentiation in cod based on
      microsatellites are inflated, and in some cases relationships among populations
      are obscured by one or more loci being the subject to hitch-hiking selection.
      Likewise, temporal estimates of effective population sizes in Atlantic cod may be
      flawed. We recommend, generally, to use a higher number of microsatellite loci to
      elucidate population structure in marine fishes and other nonmodel species to
      allow for identification of outlier loci that are subject to selection.

PMID- 16968267
TI  - Comparative analysis of the within-population genetic structure in wild cherry
      (Prunus avium L.) at the self-incompatibility locus and nuclear microsatellites.
AB  - Gametophytic self-incompatibility (SI) systems in plants exhibit high
      polymorphism at the SI controlling S-locus because individuals with rare alleles
      have a higher probability to successfully pollinate other plants than individuals
      with more frequent alleles. This process, referred to as frequency-dependent
      selection, is expected to shape number, frequency distribution, and spatial
      distribution of self-incompatibility alleles in natural populations. We
      investigated the genetic diversity and the spatial genetic structure within a
      Prunus avium population at two contrasting gene loci: nuclear microsatellites and
      the S-locus. The S-locus revealed a higher diversity (15 alleles) than the eight
      microsatellites (4-12 alleles). Although the frequency distribution of S-alleles
      differed significantly from the expected equal distribution, the S-locus showed a
      higher evenness than the microsatellites (Shannon's evenness index for the S
      locus: E = 0.91; for the microsatellites: E = 0.48-0.83). Also, highly
      significant deviations from neutrality were found for the S-locus whereas only
      minor deviations were found for two of eight microsatellites. A comparison of the
      frequency distribution of S-alleles in three age-cohorts revealed no significant
      differences, suggesting that different levels of selection acting on the S-locus
      or on S-linked sites might also affect the distribution and dynamics of S
      alleles. Autocorrelation analysis revealed a weak but significant spatial genetic
      structure for the multilocus average of the microsatellites and for the S-locus,
      but could not ascertain differences in the extent of spatial genetic structure
      between these locus types. An indirect estimate of gene dispersal, which was
      obtained to explain this spatial genetic pattern, indicated high levels of gene
      dispersal within our population (sigma(g) = 106 m). This high gene dispersal,
      which may be partly due to the self-incompatibility system itself, aids the
      effective gene flow of the microsatellites, thereby decreasing the contrast
      between the neutral microsatellites and the S-locus.

PMID- 16968268
TI  - Differential patterns of morphological and molecular hybridization between
      Fraxinus excelsior L. and Fraxinus angustifolia Vahl (Oleaceae) in eastern and
      western France.
AB  - We examined large-scale patterns of morphology, genetic structure and ecological
      correlates of Fraxinus excelsior and the closely related species Fraxinus
      angustifolia in France, in order to determine the degree of hybridization between
      them. We sampled 24 populations in two putative hybrid zones (Loire and Saone),
      and five control populations of each species. We measured foliar characteristics
      of adult trees and used five nuclear microsatellites as molecular markers.
      Canonical discriminant analysis indicated that the two species differ in
      morphology, but that intermediate types are common in the Loire region but less
      frequent in the Saone region. Bayesian population assignment identified one F.
      angustifolia and two F. excelsior gene pools. Most Loire individuals clustered
      genetically with the F. angustifolia gene pool. In contrast, the Saone region
      presented individuals belonging mostly to F. excelsior pools, although the F.
      angustifolia type was frequent in certain populations. The lowest F(ST) values
      were found between the Loire and F. angustifolia controls that also exhibited no
      significant isolation by distance. The proportion of the F. angustifolia gene
      pool in each locality was negatively correlated with winter temperatures,
      suggesting that a cold climate may be limiting. Hybridization is probably
      favoured by the intermediate climatic conditions in the Loire region that allow
      both species to occur, but is somewhat hampered by the harsher winters in the
      Saone area where morphological introgression has apparently not yet occurred.

PMID- 16968269
TI  - Comparative phylogeography of coastal limpets across a marine disjunction in New
      Zealand.
AB  - Cook Strait, which separates the North and South Island of New Zealand, has been
      a transient, but re-occurring feature of the New Zealand land mass throughout the
      Pleistocene, maintaining its current width and depth for the past 5000 years.
      Historic land fragmentation coupled with the complex hydrography of the Greater
      Cook Strait region has created both biogeographic and phylogeographic
      disjunctions between the North and South Island in several marine species. Here
      we use mitochondrial cytochrome b DNA sequences of three endemic intertidal
      limpets, Cellana ornata, Cellana radians and Cellana flava to assess
      intraspecific phylogeographic patterns across Cook Strait and to look for
      interspecific concordance of ecological and evolutionary processes among closely
      related taxa. We sequenced 328-359 bp in 85-321 individuals from 8-31 populations
      spanning the biogeographic range of the three species. Intraspecific
      phylogeographic analyses show moderate to strong genetic discontinuity among
      North and South Island populations due to allopatric fragmentation. This pattern
      was broadly concordant across the three species and the observed divergence among
      this group of intertidal limpets (0.3-2.0%) is similar to that of previously
      studied subtidal organisms. For each species, divergence time calculations
      suggest contemporary North and South Island lineages diverged from their
      respective most recent common ancestor approximately 200 000 to 300 000 years
      before present (bp), significantly earlier than previous estimates in other
      coastal marine taxa that arose from a miscalculation of divergence time.

PMID- 16968270
TI  - Comparative phylogeography of the Veronica alpina complex in Europe and North
      America.
AB  - The Veronica alpina complex comprises eight species of alpine habitats over a
      wide range of mountain systems in the Northern Hemisphere. The occurrence of
      sympatric species in the European and North American mountain systems allowed us
      not only to investigate the effect of the ice ages on intraspecific
      phylogeographical patterns and genetic diversity in different continents of the
      Northern Hemisphere, but also to compare these patterns in closely related
      species. Plastid DNA trnL-F sequences and AFLP (amplified fragment length
      polymorphism) fingerprints were used to infer the phylogenetic history of the
      group and phylogeographical patterns within species. Hybrid origin of tetraploid
      eastern North American V. wormskjoldii from western North American V. nutans (=
      V. wormskjoldii s.l.) and Eurasian V. alpina is suggested. A number of
      phylogeographical groups have been found both in V. alpina from Europe and in V.
      nutans from western North America. Phylogeographical substructuring in the Alps
      is inferred for V. alpina but not for V. bellidioides, which is moreover
      characterized by an overall very low genetic diversity. Western North American V.
      cusickii is much more genetically diverse than its sympatric relative, V. nutans,
      an effect that is likely due to differences in the breeding system. Populations
      of V. nutans are differentiated into three groups, those from the Cascades and
      from the southern and the northern Rocky Mountains. Genetic diversity seems to be
      higher in the North American V. nutans than in the morphologically and
      ecologically similar European V. alpina. A possible scenario to explain this
      pattern is suggested.

PMID- 16968271
TI  - Phylogeographic analyses of a circumarctic coastal and a boreal lacustrine mysid
      crustacean, and evidence of fast postglacial mtDNA rates.
AB  - Phylogeographic structures of two weakly dispersing Mysis sibling species, one
      with a circumarctic coastal, the other with a boreal lacustrine-Baltic
      distribution, were studied from mitochondrial cytochrome c oxidase subunit I
      (COI) gene sequences. Mysis segerstralei showed high overall diversity and little
      phylogeographic structure across the Arctic, indicating late-glacial dispersal
      among coastal and lake populations from Alaska, Siberia and the north of Europe.
      A strongly divergent refugial lineage was however identified in Beringia. The
      boreal 'glacial relict'Mysis salemaai in turn displayed clear structuring among
      postglacially isolated Scandinavian lake populations. The inferred pattern of
      intralake mitochondrial DNA (mtDNA) monophyly in Scandinavia suggested relatively
      small population sizes and a remarkably fast postglacial mtDNA divergence rate
      (0.27% per 10 000 years). Nevertheless, the broader phylogeographic pattern did
      not support distinct eastern and western glacial refugia in Northern Europe,
      unlike in some other aquatic taxa. In all, the two species comprised three
      equidistant mitochondrial lineages (approximately 2% divergence), corresponding
      to M. salemaai, to the bulk of M. segerstralei, and to the Beringian M.
      segerstralei lineage. The lack of reciprocal monophyly of the two species in
      respect to their mitochondrial genealogy could indicate postspeciation
      mitochondrial introgression, also exemplified by an evidently more recent capture
      of M. segerstralei mitochondria in a Karelian population of M. salemaai. Overall,
      the data suggest that the continental boreal M. salemaai has a relatively recent
      ancestry in arctic coastal waters, whereas two other boreal 'glacial relict'Mysis
      sibling species in Europe (Mysis relicta) and North America (Mysis diluviana)
      have colonized inland waters much earlier (approximately 8% COI divergence).

PMID- 16968274
TI  - An unexpected recent ancestor of unisexual Ambystoma.
AB  - Previous research has shown that members of the unisexual hybrid complex of the
      genus Ambystoma possess a mitochondrial genome that is unrelated to their nuclear
      parental species, but the origin of this mitochondrion has remained unclear. We
      used a 744-bp fragment of the mitochondrial gene cytochrome b within a
      comparative phylogenetic framework to infer the maternal ancestor of this
      unisexual lineage. By examining a broader range of species than has previously
      been compared, we were able to uncover a recent maternal ancestor to this
      complex. Unexpectedly, Ambystoma barbouri, a species whose nuclear DNA has not
      been identified in the unisexuals, was found to be the recent maternal ancestor
      of the individuals examined through the discovery of a shared mtDNA haplotype
      between the unisexuals and A. barbouri. Based on a combination of sequence data
      and glacial patterning, we estimate that the unisexual lineage probably
      originated less than 25 000 years ago. In addition, all unisexuals examined
      showed extremely similar mtDNA sequences and the resultant phylogeny was
      consistent with a single origin for this lineage. These results confirm previous
      suggestions that the unisexual Ambystoma complex was formed from a hybridization
      event in which the nuclear DNA of the original maternal species was subsequently
      lost.

PMID- 16968272
TI  - Incomplete cryptic speciation between intertidal and subtidal morphs of Acrocnida
      brachiata (Echinodermata: Ophiuroidea) in the Northeast Atlantic.
AB  - The brittle-star Acrocnida brachiata (Montagu) lives in sandy-bottom habitat of
      both intertidal and subtidal zones along the coasts of the northwestern Europe.
      An allozyme frequency-based survey (five enzyme loci) was combined with a
      mitochondrial (mt) COI haplotype analysis (598-bp sequences) on 17 populations to
      trace back past colonization pathways from the actual population structure of the
      species. Both genetic markers display a sharp genetic break between intertidal
      (clade I) and subtidal populations (clade S). This break corresponds to an allele
      frequency inversion at three enzyme loci (Hk, Pgm and Pgi) and a deep divergence
      of about 20% in mtCOI sequences between most of the intertidal populations and
      other samples. The geographic distribution of clade I seems to be more restricted
      than clade S as it is absent from the intertidal of the eastern English Channel
      and North Sea and may be replaced by clade S in south Brittany. Applying
      previously published rates of mutation, divergence between the two clades is
      estimated to pre-date 5 million years ago and may be due to allopatric speciation
      processes at the Mio-Pliocene transition. The occurrence of putative hybrids in a
      few localities, however, suggests incomplete cryptic speciation with secondary
      contact zones. The relative importance of colonization history vs. habitat
      specialization are discussed in the light of neutral evolution as tested from
      mtCOI gene sequences. While differential selection seems to have contributed
      little to the separation of the lineages, it may have played a role in the
      emergence of adaptive polymorphisms in the hybrid zone. Furthermore, congruent
      spatial patterns of differentiation were observed in both clades suggesting a
      recent increase in population size. These findings are in agreement with a recent
      expansion of the populations during or after the formation of the English
      Channel, from a southern refuge for the subtidal clade whereas the intertidal
      clade may have persisted further north. As previously suspected for a species
      with a very short pelagic larval phase, contemporary gene flow between distant or
      adjacent populations appears to be extremely reduced or even absent.

PMID- 16968273
TI  - Spatial and temporal genetic structure of the planktonic Sagitta setosa
      (Chaetognatha) in European seas as revealed by mitochondrial and nuclear DNA
      markers.
AB  - Little is known about the spatial and temporal scales at which planktonic
      organisms are genetically structured. A previous study of mitochondrial DNA
      (mtDNA) in the holoplanktonic chaetognath Sagitta setosa revealed strong
      phylogeographic structuring suggesting that Northeast (NE) Atlantic,
      Mediterranean and Black Sea populations are genetically disjunct. The present
      study used a higher sampling intensity and a combination of mitochondrial and
      four microsatellite markers to reveal population structuring between and within
      basins. Between basins, both marker sets indicated significant differentiation
      confirming earlier results that gene flow is probably absent between the
      respective S. setosa populations. At the within-basin scale, we found no evidence
      of spatial or temporal structuring within the NE Atlantic. In the Mediterranean
      basin, both marker sets indicated significant structuring, but only the mtDNA
      data indicated a sharp genetic division between Adriatic and all other
      Mediterranean populations. Data were inconclusive about population structuring in
      the Black Sea. The levels of differentiation indicated by the two marker sets
      differed substantially, with far less pronounced structure detected by
      microsatellite than mtDNA data. This study also uncovered the presence of highly
      divergent mitochondrial lineages that were discordant with morphology, geography
      and nuclear DNA. We thus propose the hypothesis that highly divergent
      mitochondrial lineages may be present within interbreeding S. setosa populations.

PMID- 16968275
TI  - Evolution of rattlesnakes (Viperidae; Crotalus) in the warm deserts of western
      North America shaped by Neogene vicariance and Quaternary climate change.
AB  - During Pleistocene, the Laurentide ice sheet rearranged and diversified biotic
      distributions in eastern North America, yet had minimal physical impact in
      western North America where lineage diversification is instead hypothesized to
      result from climatic changes. If Pleistocene climatic fluctuations impacted
      desert species, the latter would reflect patterns of restricted gene flow
      concomitant with indications of demographic bottlenecks. Accordingly, molecular
      evidence for refugia should be present within these distributions and for
      subsequent range expansions as conditions improved. We sought answers to these
      questions by evaluating mitochondrial DNA (mtDNA) sequences from four species of
      rattlesnakes [Crotalus mitchellii (speckled rattlesnake), Crotalus cerastes
      (sidewinder), Crotalus tigris (tiger rattlesnake), Crotalus ruber (red diamond
      rattlesnake)] with distributions restricted to desert regions of southwestern
      North America. We inferred relationships using parsimony and maximum likelihood,
      tested intraspecific clades for population expansions, applied an isolation-with
      migration model to determine bi-directional migration rates (m) among regions,
      and inferred divergence times for species and clades by applying a semiparametric
      penalized likelihood approach to our molecular data. Evidence for significant
      range expansion was present in two of eight regions in two species (Crotalus
      mitchellii pyrrhus, C. tigris region north). Two species (C. cerastes, C.
      mitchellii) showed a distribution concomitant with northward displacement of Baja
      California from mainland Mexico, followed by vicariant separation into subclades.
      Effects of Pleistocene climate fluctuations were found in the distributions of
      all four species. Three regional diversification patterns were identified: (i)
      shallow genetic diversity that resulted from Pleistocene climatic events (C.
      tigris, C. ruber); (ii) deep Pleistocene divisions indicating allopatric
      segregation of subclades within refugia (C. mitchellii, C. cerastes); and (iii)
      lineage diversifications that extended to Pliocene or Late Miocene (C.
      mitchellii, C. cerastes). Clade-diversifying and clade-constraining effects
      impacted the four species of rattlesnakes unequally. We found relatively high
      levels of molecular diversification in the two most broadly distributed species
      (C. mitchellii, C. cerastes), and lower levels of genetic diversification in the
      two species (C. tigris, C. ruber) whose ranges are relatively more restricted.
      Furthermore, in several cases, the distributions of subspecies were not congruent
      with our molecular information. We suggest regional conservation perspectives for
      southwestern deserts cannot rely upon subspecies as biodiversity surrogates, but
      must instead employ a molecular and deep historical perspective as a primary
      mechanism to frame biodiversity reserves within this region.

PMID- 16968276
TI  - Mitochondrial DNA phylogeography of Lissotriton boscai (Caudata, Salamandridae):
      evidence for old, multiple refugia in an Iberian endemic.
AB  - In Europe, southern peninsulas served as refugia during cold periods in the
      Pleistocene, acting both as centres of origin of endemisms and as sources from
      which formerly glaciated areas were recolonized during interglacial periods.
      Previous studies have revealed that within the main refugial areas, intraspecific
      lineages often survived in allopatric refugia. We analysed two mitochondrial
      markers (nad4, control region, approximately 1.4 kb) in 103 individuals
      representing the entire distribution of Lissotriton boscai, a newt endemic to the
      western Iberian Peninsula. We inferred the evolutionary history of the species
      through phylogenetic, phylogeographic and historical demographic analyses. The
      results revealed unexpected, deep levels of geographically structured genetic
      variability. We identified two main evolutionary lineages, each containing three
      well-supported clades. The first historical split involved populations from
      central-southwestern coastal Portugal and the ancestor of all the remaining
      populations around 5.8 million years ago. Both lineages were subsequently
      fragmented into different population groups between 2.5 and 1.2 million years
      ago. According to nested clade analysis, at lower hierarchical levels the
      patterns suggest restricted gene flow with isolation by distance, whereas at
      higher levels the clades exhibit signatures of contiguous range expansion.
      Bayesian Skyline Plots show recent bottlenecks, followed by demographic
      expansions in all lineages. The significant genetic structure found is consistent
      with long-term survival of populations in allopatric refugia, supporting the
      'refugia-within-refugia' scenario for southern European peninsulas. The
      comparison of our results with other co-distributed species highlights the
      generality of this hypothesis for the Iberian herpetofauna and suggests that
      Mediterranean refuges had more relevance for the composition and distribution of
      present biodiversity patterns than currently acknowledged. We briefly discuss the
      taxonomic and conservation implications of our results.

PMID- 16968277
TI  - Patterns of recurrent evolution and geographic parthenogenesis within apomictic
      polyploid Easter daises (Townsendia hookeri).
AB  - Geographic patterns of parthenogenesis and the number of transitions from sexual
      diploidy to asexual (apomictic) autopolyploidy were examined for 40 populations
      of the Easter daisy, Townsendia hookeri. Analyses of pollen diameter and
      stainability characterized 15 sexual diploid and 25 apomictic polyploid
      populations from throughout the plant's western North American range. Sexual
      diploids were restricted to two Wisconsin refugia: Colorado/Wyoming, south of the
      ice sheets, and northern Yukon/Beringia. Chloroplast DNA sequencing uncovered 17
      polymorphisms within the ndhF gene and trnK intron, yielding 10 haplotypes.
      Phylogenetic analyses indicated that five exclusively polyploid haplotypes were
      derived from four haplotypes that are shared among ploidies, conservatively
      inferring a minimum of four origins of apomictic polyploidy. Three of these
      apomictic polyploid origins were derived from southern sexual diploids, while the
      fourth origin was derived from northern sexual diploids. Analyses of regional
      diversity were suggestive of a formerly broad distribution for sexual diploids
      that has become subsequently fragmented, possibly due to the last round of
      glaciation. As sexual diploids were exclusively found north and south of the
      glacial maximum, while formerly glaciated areas were exclusively inhabited by
      asexual polyploids derived from both northern and southern sexual lineages, it is
      more likely that patterns of glaciation, as opposed to a particular latitudinal
      trend, played a causal role in the establishment of the observed pattern of
      geographic parthenogenesis in Easter daisies.

PMID- 16968278
TI  - Genetic enrichment of the arctic clonal plant Saxifraga cernua at its southern
      periphery via the alpine sexual Saxifraga sibirica.
AB  - Isolation of populations at the margins of a species range may lead to decreasing
      genetic diversity via genetic drift and inbreeding. Hybridization between
      peripheral populations of two species can, however, counteract genetic
      impoverishment. The mainly clonal, polyploid plant Saxifraga cernua has a wide
      arctic distribution but also extends southwards into alpine sites. In the Ural
      Mountains, its peripheral distribution overlaps with that of its sexually
      reproducing, diploid relative Saxifraga sibirica, and fertile polyploids of more
      or less intermediate appearance are found in this overlap zone. We used amplified
      fragment length polymorphism (AFLP) analysis to address the potential impact of
      interspecific gene flow on genetic diversity in the peripheral populations. A
      total of 149 plants from 17 populations along a 1650 km south-north gradient were
      analysed for 253 markers. The results suggest that three Middle Ural populations
      containing fertile and morphologically more or less intermediate plants have been
      affected by hybridization. All of these plants formed a strongly supported (100%)
      group with S. cernua in a neighbour-joining tree, but their AFLP phenotypes
      assigned either to S. cernua or to artificial (simulated) F(1) hybrids between S.
      cernua and S. sibirica in multilocus assignment tests. The three populations were
      highly diverse with virtually every plant representing a distinct AFLP phenotype,
      providing additional evidence for formation of later-generation hybrids and/or
      backcrossing to S. cernua. In contrast, other peripheral populations of S. cernua
      were typically monoclonal, suggesting that hybridization with S. sibirica can
      increase genetic diversity in S. cernua at its southern periphery.

PMID- 16968279
TI  - Genetic isolation and divergence in sexual traits: evidence for the northern
      rockhopper penguin Eudyptes moseleyi being a sibling species.
AB  - The taxonomic status of populations of rockhopper penguins (Eudyptes chrysocome)
      is still enigmatic. Northern populations differ from southern ones in breeding
      phenology, song characteristics and head ornaments used as mating signals. We
      conducted a molecular analysis using mitochondrial DNA sequencing to test if
      there is a gene flow barrier between northern (subtropical) populations and
      southern (subantarctic) populations in relation to the Subtropical Convergence, a
      major ecological boundary for marine organisms. Sequences of the control region
      and the ND2 gene were analysed in rockhopper penguins and in the macaroni penguin
      (Eudyptes chrysolophus), a closely related species. Genetic distances and
      phylogenetic analyses showed a clear split into three clades, two rockhopper
      clades and the macaroni penguin. Moreover, Theta(ST) and gene flow estimates also
      suggested genetic structuring within the northern rockhoppers. Our results add
      further support to the notion that the two rockhopper penguin taxa, often
      considered as two subspecies, can be recognized as two species E. chrysocome and
      E. moseleyi. The divergence in mating signals found between these two taxa seems
      to have occurred recently and relatively rapidly. Thus, the behavioural changes
      may have been enough to isolate these taxa without the need for morphological
      differentiation. The findings have important conservational implications, since
      E. moseleyi is far less abundant than E. chrysocome, but more populations may
      warrant an uplisting to endangered status if full species status should be
      recognized for more subpopulations.

PMID- 16968280
TI  - Phylogeography and Pleistocene refugia of the adder (Vipera berus) as inferred
      from mitochondrial DNA sequence data.
AB  - In order to contribute to the debate about southern glacial refugia used by
      temperate species and more northern refugia used by boreal or cold-temperate
      species, we examined the phylogeography of a widespread snake species (Vipera
      berus) inhabiting Europe up to the Arctic Circle. The analysis of the
      mitochondrial DNA (mtDNA) sequence variation in 1043 bp of the cytochrome b gene
      and in 918 bp of the noncoding control region was performed with phylogenetic
      approaches. Our results suggest that both the duplicated control region and
      cytochrome b evolve at a similar rate in this species. Phylogenetic analysis
      showed that V. berus is divided into three major mitochondrial lineages, probably
      resulting from an Italian, a Balkan and a Northern (from France to Russia)
      refugial area in Eastern Europe, near the Carpathian Mountains. In addition, the
      Northern clade presents an important substructure, suggesting two sequential
      colonization events in Europe. First, the continent was colonized from the three
      main refugial areas mentioned above during the Lower-Mid Pleistocene. Second,
      recolonization of most of Europe most likely originated from several refugia
      located outside of the Mediterranean peninsulas (Carpathian region, east of the
      Carpathians, France and possibly Hungary) during the Mid-Late Pleistocene, while
      populations within the Italian and Balkan Peninsulas fluctuated only slightly in
      distribution range, with larger lowland populations during glacial times and with
      refugial mountain populations during interglacials, as in the present time. The
      phylogeographical structure revealed in our study suggests complex recolonization
      dynamics of the European continent by V. berus, characterized by latitudinal as
      well as altitudinal range shifts, driven by both climatic changes and competition
      with related species.

PMID- 16968281
TI  - Size breeds success: multiple paternity, multivariate selection and male
      semelparity in a small marsupial, Antechinus stuartii.
AB  - Mating in the marsupial genus Antechinus is a synchronous annual event that is
      characterized by monoestry in females and abrupt postmating mortality in males.
      Male semelparity (multiple copulations during a single breeding season per
      lifetime) is often assumed to occur as a consequence of the intense mating effort
      expended by males in the rut, but the forces selecting for this remain elusive.
      Here, we investigate selection in male brown antechinus, Antechinus stuartii, and
      test two hypotheses for the evolution of semelparity: intermale competition and
      sperm competition. If intermale competition drives semelparity, we predicted that
      males would be under strong selection for large body size. If sperm competition
      is important, we predicted that selection would be strongest on scrotal size, a
      surrogate for testes volume. Using microsatellite markers, we found that 92% of
      females in free-living conditions mated with multiple males, producing litters of
      eight that had up to four fathers. These observations confirm the potential for
      sperm competition. Using selection analysis, we then found paternity success in
      119 males to be related most strongly to body mass and scrotal size, thus
      providing support for both hypotheses. Large males presumably experience
      increased paternity success by gaining more matings or prolonged copulations via
      mate guarding, while large testes may allow increased sperm investment per
      copulation. Increased levels of free corticosteroid hormones in males facilitate
      the extreme mating effort during the short period of rut, but lead to immune
      suppression and consequently to the phenomenon of postmating mortality.

PMID- 16968282
TI  - Dispersal, philopatry and intergroup relatedness: fine-scale genetic structure in
      the white-breasted thrasher, Ramphocinclus brachyurus.
AB  - Dispersal is a fundamental process influencing evolution, social behaviour, and
      the long-term persistence of populations. We use both observational and genetic
      data to investigate dispersal, kin-clustering and intergroup relatedness in the
      white-breasted thrasher, Ramphocinclus brachyurus, a cooperatively breeding bird
      that is globally endangered. Mark-resighting data suggested sex-biased dispersal,
      with females dispersing over greater distances while males remained philopatric.
      Accordingly, spatial autocorrelation analysis showed highly significant fine
      scale genetic structure among males, but not among females. This fine-scale
      genetic structuring of the male population resulted in very high levels of
      relatedness between dominant males at neighbouring nests, similar to that seen
      within cooperative groups in many species where kin selection is cited as a cause
      of cooperation. By implication, between-group as well as within-group cooperation
      may be important, potentially creating a feedback loop in which short-distance
      dispersal by males leads to the formation of male kin clusters that in turn
      facilitate nepotistic interactions and favour further local recruitment. The
      strength of spatial autocorrelation, as measured by the autocorrelation
      coefficient, r, was approximately two to three times greater than that reported
      in previous studies of animals. Relatively short dispersal distances by both
      males and females may have a negative impact on the white-breasted thrasher's
      ability to colonize new areas, and may influence the long-term persistence of
      isolated populations. This should be taken into account when designating
      protected areas or selecting sites for habitat restoration.

PMID- 16968283
TI  - Genetic breeding system and investment patterns within nests of Dawson's
      burrowing bee (Amegilla dawsoni) (Hymenoptera: Anthophorini).
AB  - Dawson's burrowing bee is a large solitary ground-nesting bee endemic to the arid
      zone of Western Australia. In this study, we use microsatellite markers to
      analyse the genotypes of offspring from individual nests to determine the number
      of effective mates for each female. From these data we have determined that
      females almost certainly mate only once which is consistent with male
      reproductive tactics that include protandry and intense male-male competition for
      access to virgin females. We also use the molecular data to show that the nesting
      female is the mother of all the offspring of her nest and that brood parasitism
      is unlikely in this species. The data indicate that females make daughters at the
      beginning of the season followed by large sons in the middle, and then small sons
      at the end. Females often place one brood cell directly above another. The
      distribution of sex and morph in these doublets follows a pattern with most
      containing a female on the bottom and a minor male on the top, followed by almost
      equal numbers of female on top of female and minor male on top of major male.
      This pattern is likely favoured by emergence patterns, with males emerging before
      females and minor males emerging before major males. We suggest that although
      minor males have low reproductive success, their production may nonetheless be
      beneficial in that minor males open up emergence tunnels for their larger and
      reproductively more valuable siblings. In addition, minor males may be a best of
      a bad job product arising from changes in the costs to nesting females of
      gathering brood provisions over the course of the flight season.

PMID- 16968284
TI  - Natural selection and climate change: temperature-linked spatial and temporal
      trends in gene frequency in Fagus sylvatica.
AB  - Rapid increases in global temperature are likely to impose strong directional
      selection on many plant populations, which must therefore adapt if they are to
      survive. Within populations, microgeographic genetic differentiation of
      individuals with respect to climate suggests that some populations may adapt to
      changing temperatures in the short-term through rapid changes in gene frequency.
      We used a genome scan to identify temperature-related adaptive differentiation of
      individuals of the tree species Fagus sylvatica. By combining molecular marker
      and dendrochronological data we assessed spatial and temporal variation in gene
      frequency at the locus identified as being under selection. We show that gene
      frequency at this locus varies predictably with temperature. The probability of
      the presence of the dominant marker allele shows a declining trend over the
      latter half of the 20th century, in parallel with rising temperatures in the
      region. Our results show that F. sylvatica populations may show some capacity for
      an in situ adaptive response to climate change. However as reported ongoing
      distributional changes demonstrate, this response is not enough to allow all
      populations of this species to persist in all of their current locations.

PMID- 16968285
TI  - When is a hybrid a hybrid? A counter-reply to Wallace et al.

PMID- 16968286
TI  - Allen Denver Russell Memorial Lecture, 2006. The use of microbicides in infection
      control: a critical look at safety, testing and applications.
AB  - Microbial pathogens continue as major threats to health. Indeed, many ongoing
      societal changes are enhancing our vulnerability and exposure to several frank
      and opportunistic pathogens. This, together with rampant antimicrobial resistance
      and reduced prospects for newer drugs and vaccines, is forcing a higher reliance
      on microbiocides in infection prevention and control. That this reliance may not
      be well-founded becomes apparent from a closer look at current ways of testing
      and registering microbiocides, their label claims as well as human and
      environmental safety of certain widely used microbicidal chemicals. Many methods
      to test microbiocides for registration are flawed and/or entail test conditions
      irrelevant to field use. Pathogens listed on product labels may not be among
      those amenable to interruption through microbiocide use. The wide variations and
      discrepancies in existing national/regional regulations for registering
      microbiocides for sale stifle innovation. This is a critical look at the above
      mentioned issues with emphasis on chemicals meant for use on environmental
      surfaces and medical devices. It highlights better ways to test microbiocides and
      to attain global harmonization of testing and product registration. It also
      details the known and potential dangers of microbiocide use and what to consider
      in choosing such formulations for optimal safety and effectiveness. End users are
      advised to be more critical and prudent in the selection and application of
      microbicidal chemicals, manufacturers are encouraged to explore infection control
      products and technologies that are safer in the workplace and for the
      environment, and regulators are urged to review and update the requirements and
      procedures for premarket review of microbiocide efficacy data and label claims.
      Independent investigations are also urgently needed to document the proportion of
      nosocomial infections that would be amenable to prevention through chemical
      disinfection of environmental surfaces.

PMID- 16968287
TI  - Differential identification of Bacillus anthracis from environmental Bacillus
      species using microarray analysis.
AB  - AIMS: To determine whether microarray analysis could be employed for the
      differential identification of a range of environmental Bacillus sp. from four
      strains of Bacillus anthracis. METHODS AND RESULTS: Oligonucleotide probes were
      designed that were specific to virulence factor genes of B. anthracis (pag, lef
      and cap), the variable number tandem repeat region of the B. anthracis vrrA gene
      and to the 16S-23S rRNA intergenic transcribed spacer region (ITS) and
      pleiotropic regulator (plcR) regions of the Bacillus cereus subgroup species.
      Generic probes were also designed to hybridize with conserved regions of the 16S
      rRNA genes of Bacillus (as a positive control), Neisseria sp., Pseudomonas sp.,
      Streptococcus sp., Mycobacterium sp. and to all members of the Enterobacteriaceae
      to allow simultaneous detection of these bacteria. Identification of B. anthracis
      was found to rely entirely on hybridization of DNA specific to regions of the
      pag, lef and cap genes. Cross-reaction was observed between B. anthracis and
      other Bacillus species with all the other Bacillus probes tested. Results
      obtained using microarray hybridizations were confirmed using conventional
      microbiological techniques and found to have very high comparability.
      CONCLUSIONS: Microarray-based assays are an effective method for the
      identification of B. anthracis from mixed-culture environmental samples without
      problems of false-positivity that have been observed with conventional PCR
      assays. SIGNIFICANCE AND IMPACT OF THE STUDY: Identification of environmental
      Bacillus sp. by conventional PCR is prone to potential for reporting false
      positives. This study provides a method for the exclusion of such isolates.

PMID- 16968288
TI  - Isolation of an ethanol-tolerant endospore-forming Gram-negative Brevibacillus
      sp. as a covert contaminant in grape tissue cultures.
AB  - AIMS: To characterize the alcohol-surviving bacterial isolate ARBG1 from in vitro
      grapes (Vitis vinifera). METHODS AND RESULTS: Two bacterial strains that survived
      in covert form in grape cultures were isolated from the spent alcohol used for
      disinfecting the tools of which one (ARBG2) was characterized earlier. The
      present study describes characterization of the second isolate, ARBG1. Nutrient
      agar (NA)-derived colonies of ARBG1 displayed consistently Gram-negative staining
      rods (2-4x0.5-0.6 micro) substantiated by KOH mucoid thread test. Older cultures
      (3-7 days) showed emergence of Gram-negative staining, oblong, phase-refractile
      cells with ellipsoidal spores. The growth and sporulation were modified by growth
      medium and incubation temperature with the optimum around 37 degrees C.
      Identification attempts involving microscopic, biochemical, Biolog or fatty acid
      profiling approaches brought in mixed and inconclusive results. PCR amplification
      of 16S rDNA was not successful with the standard primers 27F and 1492R but with
      27F and a modified primer ARBG1-RP1. The identity of the isolate was established
      as Brevibacillus sp. based on partial 16S rDNA sequence data from eight single
      colonies with Gram-positive Brevibacillus choshinensis as the closest match
      (99.5%). Spotting tests on NA employing spore suspension in aqueous ethanol (0%,
      25%, 50%, 60%, 70%, 80% or 90%, v/v) indicated unhindered bacterial-survival in
      alcohol for 1 month, and that at 2 or 4 months revealed 90% ethanol as more
      sporicidal than lower levels, corroborated by plating results. Grape
      microcuttings inoculated with ARBG1 showed substantial general colonization of
      shoots, roots and medium but low endophytic colonization. CONCLUSIONS: The rare
      type of spore-producing consistently Gram-negative bacterial isolate ARBG1 was
      identified as Brevibacillus sp. based on 16S rDNA sequence similarity. The
      alcohol-defying organism was nonpathogenic and survived in covert form in grape
      cultures. Aqueous 90% ethanol appeared more sporicidal than lower levels.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Characterization of an unusual endospore
      forming Gram-negative bacterium, observation that some bacteria may fall outside
      the purview of standard 16S rDNA primers, elucidation of the threats of covert
      bacteria in plant tissue cultures and alcohol-mediated lateral transmission of
      spore formers, and the revelation that 70-80% ethanol may not be the most
      effective bactericidal concentration for all bacteria.

PMID- 16968289
TI  - Optimization of activation conditions of Rhodobacter sphaeroides in hydrogen
      generation process.
AB  - AIMS: To examine the effects of the culture age, illuminance intensity and
      changes in these parameters during activation on hydrogen generation process
      carried out by purple nonsulfur Rhodobacter sphaeroides bacteria. METHODS AND
      RESULTS: The following parameters were determined in all experiments: the amount
      of hydrogen evolved (measured using gas chromatography), biomass increase as dry
      mass, pH values and consumption of organic substance as chemical oxygen demand
      (COD). The medium used in the process of activation and hydrogen generation
      contained malic acid (15 mmol) and sodium glutamate (2 mmol). The optimum age of
      bacteria was 12-24 h and the best intensity of illuminance was found to be 5 cd
      sr m-2 on activation and 9 cd sr m-2 on hydrogen generation. These conditions
      provided hydrogen evolution of 1.39 l l-1 of the medium with the highest specific
      hydrogen production of 0.146 l H2 l-1 medium h-1 g-1 inoculum. An increase in the
      illuminance intensity resulted in a slight inhibition of the process.
      CONCLUSIONS: The activation stage of bacteria has a significant effect on the
      parameters of hydrogen photogeneration. The optimization of the activation stages
      allowed a shortening of the time of hydrogen generation and of the period after
      which hydrogen evolution starts. SIGNIFICANCE AND IMPACT OF THE STUDY: An
      innovative method of bacteria activation before the initiation of the hydrogen
      generation process has been used to optimize this process. The shortening of the
      process duration as well as the twice higher hydrogen yield can help in the
      designing of other systems (including also those operating under solar
      irradiation) in which R. sphaeroides bacteria are to be applied.

PMID- 16968290
TI  - FT-IR microspectroscopy for early identification of some clinically relevant
      pathogens.
AB  - AIMS: To investigate the potentials and limitations of Fourier transform-infrared
      (FT-IR) microspectroscopy as a tool to identify, at the level of microcolonies,
      pathogenic bacteria frequently isolated in the clinical environment. METHODS AND
      RESULTS: A total of 1570 FT-IR spectra from 164 gram-positive and gram-negative
      bacteria isolated from patients were recorded from 6 to 10-h old microcolonies of
      50-150 microm size. A classification of 100% was obtained for the most frequent
      gram-positive bacteria, such as Staphylococcus aureus, Staphylococcus
      epidermidis, Enterococcus faecalis, and Enterococcus faecium at the species
      level. An average accuracy of about 80% was reached with Gram negative bacteria
      from the Enterobacteriaceae and Pseudomonaceae families; Enterobacter aerogenes,
      Enterobacter cloacae, Klebsiella spp., and Citrobacter koseri; and Proteus
      mirabilis and Escherichia coli. Results were comparable with FT-IR measurements
      on dried suspensions from 18-h cultures. CONCLUSIONS: Early identification of
      young microcolonies is feasible with FT-IR microscopy with a very high accuracy
      for gram-positive bacteria. Some improvement in the transfer of microcolonies is
      necessary to increase the accuracy for gram-negative bacteria. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Combination of FT-IR microscopy and multivariate data
      analysis could be a complementary, rapid, and reliable tool for screening and
      discriminating, at species and subspecies level, micro-organisms of clinical,
      food-borne, or environmental origins.

PMID- 16968291
TI  - Genotypic diversity in a localized population of Ralstonia solanacearum as
      revealed by random amplified polymorphic DNA markers.
AB  - AIMS: To assess genotypic diversity within Ralstonia solanacearum isolates of a
      single field. METHODS AND RESULTS: A total of 44 field isolates and 22 in vitro
      generated clones of R. solanacearum were studied for genotypic diversity by
      random amplified polymorphic DNA (RAPD) technique. Genomic DNA of these isolates
      and clones was extracted by proteinase-K-SDS lysis mini-prep method. RAPD
      analysis was done with 30 decamer primers. The data were analysed using NTSYSpc
      2.02h software. Forty-two out of 44 field isolates and all the clonal isolates
      were identified as distinct genotypes at 70% similarity level. CONCLUSION: Very
      high level of genome variability was observed within the field and clonal
      isolates of R. solanacearum. This might be a reason for the wide host range of
      this bacterium and for quick breakdown of wilt resistance in host plants.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The results suggest that it would be
      difficult to design specific diagnostic protocol for R. solanacearum even for a
      localized population and to breed cultivars with broad-spectrum resistance.

PMID- 16968292
TI  - The kinetics of Lagenidium giganteum growth in liquid and solid cultures.
AB  - AIMS: Production of the mosquito biolarvacide Lagenidium giganteum in solid
      culture has been proposed as an economic alternative to production in liquid
      culture because of observations of improved shelf life and efficacy upon storage.
      Understanding the differences between these production systems and estimating
      growth rate in solid culture are important for commercialization. In order to
      address these needs a logistic model was developed to describe the growth
      kinetics of L. giganteum produced in solid and liquid cultures. METHODS AND
      RESULTS: Kinetic parameters in the logistic model were estimated by nonlinear
      regression of CO2 evolution rate (CER) and biomass data from solid and liquid
      cultivation experiments. Lagenidium giganteum biomass was measured using DNA
      extracted directly from samples. The logistic model was fit to experimental
      biomass and CER data with low standard errors for parameter estimates. The model
      was validated in two independent experiments by examining prediction of biomass
      using on-line CER measurements. CONCLUSIONS: There were significant differences
      between maximum biomass density, maintenance coefficients, and specific growth
      rates for liquid and solid cultures. The maximum biomass density (mg dw ml-1) was
      11 times greater for solid cultivation compared with liquid cultivation of L.
      giganteum; however, the maintenance coefficient (mg CO2 h-1 (mg dw)-1) was six
      times greater for liquid cultivation than in solid cultivation. The specific
      growth rate at 30 degrees C was approximately 30% greater in liquid cultivation
      compared with solid cultivation. Slower depletion of substrate and lower
      endogenous metabolism may explain the longer shelf life of L. giganteum produced
      in solid culture. SIGNIFICANCE AND IMPACT OF THE STUDY: A simple logistic model
      was developed which allows real-time estimation of L. giganteum biomass from on
      line CER measurements. Parameter estimates for liquid and solid cultivation
      models also elucidated observations of longer shelf life for production in solid
      culture.

PMID- 16968293
TI  - Composting is an effective treatment option for sanitization of Phytophthora
      ramorum-infected plant material.
AB  - AIMS: To determine the effects of heat and composting treatments on the viability
      of the plant pathogen Phytophthora ramorum grown on both artificial and various
      natural substrates. METHODS AND RESULTS: Phytophthora ramorum was grown on V8
      agar, inoculated on bay laurel leaves (Umbellularia californica) and on woody
      tissues of coast live oak (Quercus agrifolia). Effects on growth, viability and
      survival were measured as a result of treatment in ovens and compost piles.
      Direct plating onto PARP medium and pear-baiting techniques were used to
      determine post-treatment viability. No P. ramorum was recovered at the end of the
      composting process, regardless of the isolation technique used. By using a PCR
      assay designed to detect the DNA of P. ramorum, we were able to conclude the
      pathogen was absent from mature compost and not merely suppressed or dormant.
      CONCLUSIONS: Some heat and composting treatments eliminate P. ramorum to lower
      than detectable levels on all substrates tested. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Composting is an effective treatment option for sanitization of P. ramorum
      infected plant material. Assaying for pathogen viability in compost requires a
      direct test capable of differentiating between pathogen suppression and pathogen
      elimination.

PMID- 16968294
TI  - Efficacy of solar disinfection of Escherichia coli, Shigella flexneri, Salmonella
      Typhimurium and Vibrio cholerae.
AB  - AIMS: To determine the efficacy of solar disinfection (SODIS) for enteric
      pathogens and to test applicability of the reciprocity law. METHODS AND RESULTS:
      Resistance to sunlight at 37 degrees C based on F99 values was in the following
      order: Salmonella Typhimurium>Escherichia coli>Shigella flexneri>Vibrio cholerae.
      While F90 values of Salm. Typhimurium and E. coli were similar, F99 values
      differed by 60% due to different inactivation curve shapes. Efficacy seemed not
      to be dependent on fluence rate for E. coli stationary cells. Sensitivity to mild
      heat was observed above a temperature of 45 degrees C for E. coli, Salm.
      Typhimurium and Sh. flexneri, while V. cholerae was already susceptible above 40
      degrees C. CONCLUSIONS: Salmonella Typhimurium was the most resistant and V.
      cholerae the least resistant enteric strain. The reciprocity law is applicable
      for stationary E. coli cells irradiated with sunlight or artificial sunlight.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Escherichia coli might not be the
      appropriate indicator bacterium to test the efficacy of SODIS on enteric bacteria
      and the physiological response to SODIS might be different among enteric
      bacteria. The applicability of the reciprocity law indicates that fluence rate
      plays a secondary role in SODIS efficacy. Stating inactivation efficacy with T90
      or F90 values without showing original data is inadequate for SODIS studies.

PMID- 16968295
TI  - Purification and characterization of two bacteriocins produced by lactic acid
      bacteria isolated from Mongolian airag.
AB  - AIMS: The aim of this study was to isolate and identify bacteriocin-producing
      lactic acid bacteria (LAB) issued from Mongolian airag (traditional fermented
      mare's milk), and to purify and characterize bacteriocins produced by these LAB.
      METHODS AND RESULTS: Identification of the bacteria (Enterococcus durans) was
      carried out on the basis of its morphological, biochemical characteristics and
      carbohydrate fermentation profile and by API50CH kit and 16S rDNA analyses. The
      pH-neutral cell-free supernatant of this bacterium inhibited the growth of
      several Lactobacillus spp. and food-borne pathogens including Escherichia coli,
      Staphylococcus aureus and Listeria innocua. The antimicrobial agent (enterocin A5
      11) was heat stable and was not sensitive to acid and alkaline conditions (pH 2
      10), but was sensitive to several proteolytic enzymes. Its inhibitory activity
      was completely eliminated after treatment with proteinase K and alpha
      chymotrypsin. The activity was however not completely inactivated by other
      proteases including trypsin and pepsin. Three-step purification procedure with
      high recovery yields was developed to separate two bacteriocins. The applied
      procedure allowed the recovery of 16% and 64% of enterocins A5-11A and A5-11B,
      respectively, present in the culture supernatant with purity higher than 99%. SDS
      PAGE analyses revealed that enterocin A5-11 has a molecular mass of 5000 Da and
      mass spectrometry analyses demonstrates molecular masses of 5206 and 5218 Da for
      fractions A and B, respectively. Amino acid analyses of both enterocins indicated
      significant quantitative difference in their contents in threonine, alanine,
      isoleucine and leucine. Their N-termini were blocked hampering straightforward
      Edman degradation. CONCLUSIONS: Bacteriocins A5-11A and B from Ent. durans belong
      to the class II of bacteriocins. SIGNIFICANCE AND IMPACT OF THE STUDY: Judging
      from molecular masses, amino acid composition and spectrum of activities,
      bacteriocins A5-11A and B from Ent. durans show high degree of similarity with
      enterocins L50A and L50B isolated from Enterococcus faecium (Cintas et al. 1998,
      2000) and with enterocin I produced by Ent. faecium 6T1a, a strain originally
      isolated from a Spanish-style green olive fermentation (Floriano et al. 1998).

PMID- 16968296
TI  - Binding of Fusarium mycotoxins by fermentative bacteria in vitro.
AB  - AIMS: Fusarium toxins can occur in conserved forages impairing farm animal
      performances and health. On-farm biological decontamination methods could be an
      alternative to traditional physico-chemical methods. In this work, the ability to
      remove Fusarium toxins by fermentative bacteria was evaluated in vitro. METHODS
      AND RESULTS: Twenty-nine strains of lactic (LAB) and propionic acid bacteria
      (PAB) were tested for their ability to remove deoxynivalenol (DON) and fumonisins
      B1 and B2 (FB1, FB2) from an acid, pH 4, medium. Mycotoxin removal was widespread
      for LAB, but differences among strains were large. Removal was up to 55% for DON,
      82% for FB1 and 100% for FB2. Selected strains were also capable of removing up
      to 88% zearalenone. The PAB strains were less efficient than the LAB. Binding,
      not biodegradation appeared to be the mode of action, as no toxin derivatives
      were observed and removal was not impaired in nonviable bacteria. Binding was not
      affected by pH, except for fumonisins that decreased to nearly 0% at neutral pH.
      CONCLUSIONS: Selected fermentative bacteria are able to bind main Fusarium
      mycotoxins. SIGNIFICANCE AND IMPACT OF THE STUDY: The binding ability of selected
      strains could be used to decrease the bioavailability of toxins in contaminated
      silages.

PMID- 16968297
TI  - Isolation and characterization of a Lactobacillus fermentum temperate
      bacteriophage from Chinese yogurt.
AB  - AIMS: The aim of this study was to investigate the properties of temperate
      bacteriophage of Lactobacillus fermentum, based on its morphology, restriction
      patterns, protein profile and the impact on the growth of host strain. METHODS
      AND RESULTS: With Mitomycin C, seven temperate phages were induced from
      Lactobacilli derived from Chinese yogurt. The temperate phages induced belong to
      the most common Bradley's group B, having hexagonal head and long, noncontractile
      tail. They were furthermore confirmed to be the same bacteriophage by identical
      restriction patterns. SDS-PAGE profile showed that the phage studied had one
      major structure protein about 31.9 kDa. The presence of the prophage influenced
      the cell shape and colony size of its lysogenic strain. CONCLUSIONS: The phage
      obtained had similar, but not complete identical properties with other L.
      fermentum phages reported. It influenced the growth behaviour of its lysogenic
      strain. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides some
      information about bacteriophages occurring in the Chinese yoghurt manufacture and
      contributes to our knowledge on the bacteriophage diversity in the dairy
      industry.

PMID- 16968298
TI  - Molecular analysis of Staphylococcus aureus isolates associated with
      staphylococcal food poisoning in South Korea.
AB  - AIMS: To investigate the molecular epidemiological study of Staphylococcus aureus
      from staphylococcal food poisoning (SFP) incidents in South Korea. METHODS AND
      RESULTS: Three hundred and thirty-two strains isolated from ten provinces between
      June 1999 and January 2002 were characterized by staphylococcal enterotoxin
      genes, toxic shock syndrome toxin 1 (tst) gene, and exfoliative toxin genes.
      Toxin genotypes were sea-seh (n=197), sea (n=51), sea-seg-sei (n=14), seg-sei
      (n=10), seb (n=10), seb-sed-seg-sei-sej (n=3), sea-seg-seh-sei (n=1), sea-seb
      (n=1), sea-sec (n=1), seg-sei plus eta (n=4), and sea-seg-sei plus tst (n=40).
      Most of the strains could be classified into three clusters of pulsed-field gel
      electrophoresis (PFGE) types A and B with coagulase type VII and type E with
      coagulase type IV. Of the ten sequence types (ST), ST1, ST59, and ST30 were
      frequently showed by multilocus sequence typing. CONCLUSIONS: The strain
      belonging to PFGE pattern A with sea-seh gene, coagulase VII, and ST1 was the
      most epidemic clone of SFP incidents in Korea.

PMID- 16968299
TI  - Lactobacillus casei metabolic potential to utilize citrate as an energy source in
      ripening cheese: a bioinformatics approach.
AB  - AIMS: To identify potential pathways for citrate catabolism by Lactobacillus
      casei under conditions similar to ripening cheese. METHODS AND RESULTS: A
      putative citric acid cycle (PCAC) for Lact. casei was generated utilizing the
      genome sequence, and metabolic flux analyses. Although it was possible to
      construct a unique PCAC for Lact. casei, its full functionality was unknown.
      Therefore, the Lact. casei PCAC was evaluated utilizing end-product analyses of
      citric acid catabolism during growth in modified chemically defined media (mCDM),
      and Cheddar cheese extract (CCE). Results suggest that under energy source excess
      and limitation in mCDM this micro-organism produces mainly L-lactic acid and
      acetic acid, respectively. Both organic acids were produced in CCE. Additional
      end products include D-lactic acid, acetoin, formic acid, ethanol, and diacetyl.
      Production of succinic acid, malic acid, and butanendiol was not observed.
      CONCLUSIONS: Under conditions similar to those present in ripening cheese, citric
      acid is converted to acetic acid, L/D-lactic acid, acetoin, diacetyl, ethanol,
      and formic acid. The PCAC suggests that conversion of the citric acid-derived
      pyruvic acid into acetic acid, instead of lactic acid, may yield two ATPs per
      molecule of citric acid. Functionality of the PCAC reductive route was not
      observed. SIGNIFICANCE AND IMPACT OF THE STUDY: This research describes a unique
      PCAC for Lact. casei. Additionally, it describes the citric acid catabolism end
      product by this nonstarter lactic acid bacteria during growth, and under
      conditions similar to those present in ripening cheese. It provides insights on
      pathways preferably utilized to derive energy in the presence of limiting
      carbohydrates by this micro-organism.

PMID- 16968300
TI  - Transmission routes of Salmonella Typhimurium DT 104 between 14 cattle and pig
      herds in Denmark demonstrated by molecular fingerprinting.
AB  - AIMS: Salmonella Typhimurium DT 104 is generally assumed to be spread by contact
      between live animals, e.g. by trading. The aim of the present study was to assess
      the importance of other routes of transmission in the dissemination of this
      bacterium. METHODS AND RESULTS: An outbreak among 14 cattle and pig herds located
      in a geographically narrow area in Denmark was investigated. Epidemiological
      information and disease history of the herds was obtained through interviews.
      Based on this, the hypothesis for horizontal spread was proposed, and these were
      confirmed by comparison of the pulsed field gel electrophoresis (PFGE) and the
      plasmid profiles of isolates obtained by continuous sampling over a period of
      almost 3 years. CONCLUSIONS: The study indicated that other routes might play an
      important role, than the trading of live animals, in the spread of S. Typhimurium
      DT 104 among livestock. SIGNIFICANCE AND IMPACT OF THE STUDY: Salmonella
      Typhimurium DT 104 infected herd might pose a significant risk to herds located
      within the same geographic area. In advising on how to avoid the spread of this
      bacterium, factors like person contacts, sharing of equipment and contaminated
      slurry should be focussed on in addition to infected animals.

PMID- 16968301
TI  - Survival of Escherichia coli O157:H7 in wastewater from dairy lagoons.
AB  - AIM: To determine the survival of Escherichia coli O157:H7 in dairy wastewater
      from on-site holding lagoons equipped with or without circulating aerators.
      METHODS AND RESULTS: Survival was monitored in dairy lagoon microcosms equipped
      with or without scale-size circulators. Both laboratory strains of E. coli
      O157:H7 and an isolate of E. coli H7 from wastewater had poor survival rates and
      none proliferated in water from waste lagoons with or without circulators.
      Furthermore, the decline of E. coli O157:H7 was not enhanced in those microcosms
      equipped with circulators. Strain variation in survival was observed in both
      circulated and settling waters. The decline rate of E. coli O157:H7 Odwalla
      strain increased proportionately with the inoculum load. Escherichia coli failed
      to establish itself in wastewater even after four sequential inoculations
      simulating continuous faecal input into the lagoon. The native aerobic bacteria
      survived longer with a decimal reduction time of 21.3 days vs either introduced
      or native E. coli, which declined rapidly with decimal reduction time of 0.5-9.4
      days. CONCLUSIONS: Escherichia coli O157:H7 failed to establish and proliferate
      in dairy wastewater microcosms equipped with or without circulating aerators.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study furthers our knowledge of
      pathogen survival in wastewater, and suggests that proper management of
      wastewater before its use in irrigation is essential to reduce pathogen transfer
      to crops.

PMID- 16968302
TI  - Examination of Lactobacillus plantarum lactate metabolism side effects in
      relation to the modulation of aeration parameters.
AB  - AIMS: The characterization of global aerobic metabolism of Lactobacillus
      plantarum LP652 under different aeration levels, in order to optimize acetate
      production kinetics and to suppress H2O2 toxicity. METHODS AND RESULTS: Cultures
      of L. plantarum were grown on different aeration conditions. After sugar
      exhaustion and in the presence of oxygen, lactate was converted to acetate, H2O2
      and carbon dioxide with concomitant ATP production. Physiological assays were
      performed at selected intervals in order to assess enzyme activity and vitality
      of the strain during lactic acid conversion. The maximal aerated condition led to
      fast lactate-to-acetate conversion kinetics between 8 and 12 h, but H2O2
      immediately accumulated, thus affecting cell metabolism. Pyruvate oxidase
      activity was highly enhanced by oxygen tension and was responsible for H2O2
      production after 12 h of culture, whereas lactate oxidase and NADH-dependent
      lactate dehydrogenase activities were not correlated to metabolite production.
      Limited NADH oxidase (NOX) and NADH peroxidase (NPR) activities were probably
      responsible for toxic H2O2 levels in over-aerated cultures. CONCLUSION:
      Modulating initial airflow led to the maximal specific activity of NOX and NPR
      observed after 24 h of culture, thus promoting H2O2 destruction and strain
      vitality at the end of the process. SIGNIFICANCE AND IMPACT OF THE STUDY: Optimal
      aeration conditions were determined to minimize H2O2 concentration level during
      growth on lactate.

PMID- 16968303
TI  - The use of a D-optimal design to model the effects of temperature, NaCl, type and
      acid concentration on Lactobacillus pentosus IGLAC01.
AB  - AIMS: To study the effects of temperature, NaCl and acid (HCl, citric, acetic and
      lactic) concentrations on the specific growth rate (mu), lag phase (lambda), and
      h0 of Lactobacillus pentosus IGLAC01. METHODS AND RESULTS: Response surface (RS)
      methodology (D-optimal design) was used with a dummy variable, to account for the
      different types of acids. The variable ranges were: 16-30 degrees C, 0-70 g l-1
      NaCl, and 0-5 g l-1 acid (or 0-2.5 g l-1 HCl). Time to detection from optical
      density data was used to deduce mu and lambda. The RS models for log2mu and
      log2lambda, according to acid types, were estimated and the effects of variables
      were quantified by their z-generalized values. A relationship between ln h0 with
      temperature was also found. CONCLUSIONS: The mu of L. pentosus IGLAC01 can be
      doubled by increasing temperature by 10.3 degrees C or by decreasing NaCl by 48 g
      l-1 (harmonic, averaged, z values, Z); citric was the least inhibitory acid (zmu=
      96.2) and lactic the strongest (zmu=-5.7), according to their generalized z
      values, z. A twofold lambda increase was achieved from a decrease of 3.1 degrees
      C (HCl), or 4.27 degrees C (citric) or 36 g l-1 NaCl increase (both acids)
      (expressed as zlambda ); the same effect was obtained from a decrease of 4.37
      degrees C, 54 g l-1 NaCl increase, or 10 g l-1 acetic or lactic acid additions
      (expressed as Zlambda values). SIGNIFICANCE AND IMPACT OF THE STUDY: Valuable
      information on the effects of environmental variables on the biological
      parameters of L. pentosus IGLAC01, which could be used for the optimization of
      olive, cucumber or other vegetable fermentations, is obtained.

PMID- 16968304
TI  - Improving low water activity and desiccation tolerance of the biocontrol agent
      Pantoea agglomerans CPA-2 by osmotic treatments.
AB  - AIMS: To study the improvement of tolerance to low water activity (aw) and
      desiccation during spray drying in Pantoea agglomerans cells subjected to mild
      osmotic stress during growth. METHODS AND RESULTS: The micro-organism was
      cultured in an unmodified liquid (control) or in aw-modified media, and viability
      of these cells was evaluated on unstressed (0.995) and 0.96 aw stressed solid
      media, in order to check total viability and aw stress tolerance respectively.
      Significant improvements in viability on unmodified medium were observed with
      cells grown for 24 h in NaCl 0.98 aw, glycerol 0.98 aw and 0.97 aw and for 48 h
      in NaCl 0.98 aw and 0.97 aw modified media. Both yield improvements and water
      stress tolerance were achieved with low aw media. Cells grown for 24 h in NaCl
      0.98 aw or for 48 h in NaCl 0.98 aw, 0.97 aw and 0.96 aw, glucose 0.97 aw and
      glycerol 0.97 aw showed improved aw stress tolerance in comparison with control
      cells. The best results were obtained with NaCl treatments (0.98 aw and 0.97 aw)
      which also exhibited better survival rates than control cells during spray-drying
      process and maintained their efficacy against postharvest fungal pathogens in
      apples and oranges. CONCLUSIONS: NaCl treatments are very appropriate for
      improving P. agglomerans low aw tolerance obtaining high production levels and
      maintaining biocontrol efficacy. SIGNIFICANCE AND IMPACT OF THE STUDY: Improving
      stress tolerance of biocontrol agents could be an efficient way to obtain
      consistency and maintain efficacy of biological control under practical
      conditions.

PMID- 16968305
TI  - Development of a rapid strain differentiation method for methicillin-resistant
      Staphylococcus aureus isolated in Japan by detecting phage-derived open-reading
      frames.
AB  - AIMS: To develop a rapid genotyping method for investigating outbreaks of
      methicillin-resistant strains of Staphylococcus aureus (MRSA) isolated in Japan.
      METHODS AND RESULTS: Isolates were genotyped by detecting the keeping pattern of
      16 open-reading frames (ORFs), a process we call phage ORF typing (POT). Thirteen
      of the ORFs were selected from phage genomes and one from a genomic island SaGIm
      in the genome of strain Mu50. The other two ORFs, one from Tn554 and one from
      staphylococcal cassette chromosome mec (SCCmec) type II, were used as strain
      markers. Three hundred and sixty-eight isolates from five hospitals were
      classified into 133 types by POT, whereas they were classified into 139 types by
      pulsed-field gel electrophoresis (PFGE) subtyping. The discriminatory power of
      POT (D=0.989) was equal to that of PFGE subtyping (D=0.986). CONCLUSIONS: MRSA
      isolates collected in Japan can be genotyped by detecting the keeping pattern of
      phage-derived ORFs with a discriminatory power equal to that of PFGE subtyping.
      SIGNIFICANCE AND IMPACT OF THE STUDY: MRSA isolates can be genotyped rapidly by
      detecting phage-derived ORFs. As particular pandemic clones can be found in a
      specific region, a typing method localized to a pandemic clone may be effective
      for the rapid genotyping of MRSA during outbreaks.

PMID- 16968306
TI  - Characterization of a spirochaete isolated from a case of bovine digital
      dermatitis.
AB  - AIMS: The aim of the study was to characterize a spirochaete isolated from the
      lesions of a cow with digital dermatitis (DD). METHODS AND RESULTS: The
      characterization was on the basis of its light and electron microscopic
      appearance, enzymic profile and DNA sequence analysis of its flagellin and 16S
      rRNA genes. The spirochaete was 6-8-microm long and 0.2-0.3 microm in diameter,
      and possessed seven to eight periplasmic flagella, with three to five helical
      turns. The enzymic profile of the bacterium resembles, but is not identical to
      that of Treponema brennaborense. Its flagellin gene sequence was identical to
      that of Treponema phagedenis but distinct from that of an ovine spirochaete.
      Analysis of a 1477-bp region of the 16S rRNA genes indicated that this is a
      Treponema species and that it is indistinguishable from some isolates made from
      cases of bovine DD in the United States. Finally, electron microscopy revealed
      the presence of myovirus-like bacteriophage particles in all cultures of the
      treponeme examined. CONCLUSIONS: The spirochaete isolate was identified as a
      Treponema species closely related to some isolates from the United States (by 16S
      rDNA) and to T. phagedenis (by flagellin gene sequence) and is associated with
      bacteriophage particles. SIGNIFICANCE AND IMPACT OF THE STUDY: The fact that the
      isolates with the same or very similar 16S rDNA sequences have been obtained from
      cases of bovine DD in cattle in different countries at different times, lends
      further support to the hypothesis that treponemes play a role in the pathogenesis
      of this disease.

PMID- 16968307
TI  - A nucleic acid sequence-based amplification assay for real-time detection of
      norovirus genogroup II.
AB  - AIMS: To use molecular beacon based nucleic acid sequence-based amplification
      (NASBA) to develop a rapid, sensitive, specific detection method for norovirus
      (NV) genogroupII (GII). METHODS AND RESULTS: A method to detect NV GII from
      environmental samples using real-time NASBA was developed. This method was
      routinely sensitive to 100 copies of target RNA and intermittent amplification
      occurred with as few as 10 copies. Quantitative estimates of viral load were
      possible over at least four orders of magnitude. CONCLUSIONS: The NASBA method
      described here is a reliable and sensitive assay for the detection of NV. This
      method has the potential to be linked to a handheld NASBA device that would make
      this real-time assay a portable and inexpensive alternative to bench-top, lab
      based assays. SIGNIFICANCE AND IMPACT OF THE STUDY: The development of the real
      time NASBA assay described here has resulted in a simple, rapid (<1 h),
      convenient testing format for NV. To our knowledge, this is the first example of
      a molecular beacon based NASBA assay for NV.

PMID- 16968308
TI  - Prevalence of environmental Aeromonas in South East Queensland, Australia: a
      study of their interactions with human monolayer Caco-2 cells.
AB  - AIMS: To investigate the prevalence of Aeromonas in a major waterway in South
      East Queensland, Australia, and their interactions with a gut epithelial model
      using Caco-2 cells. METHODS AND RESULTS: A total of 81 Aeromonas isolates,
      collected from a major waterway in South East Queensland, Australia, were typed
      using a metabolic fingerprinting method, and tested for their adhesion to HEp-2
      and Caco-2 cells and for cytotoxin production on Vero cells and Caco-2 cells.
      Aeromonas hydrophila had the highest (43%) and Aeromonas veronii biovar sobria
      had the lowest (25%) prevalence. Four patterns of adhesion were observed on both
      HEp-2 and Caco-2 cell lines. Representative isolates having different
      phenopathotypes (nine strains) together with two clinical isolates were tested
      for their translocation ability and for the presence of virulence genes
      associated with pathogenic Escherichia coli. The rate and degree of translocation
      across Caco-2 monolayers varied among strains and was more pronounced with LogA
      pattern. Translocation was associated with the adherence of strains to Caco-2
      cells microvilli, followed by internalization into Caco-2 cells. Two Aer. veronii
      biovar sobria strains were positive for the presence of heat-labile toxin genes,
      with one strain also positive for Shiga-like toxin gene. CONCLUSIONS: Pathogenic
      strains of Aeromonas carrying one or more virulence characteristics are highly
      prevalent in the waterways studied and are capable of translocating across a
      human enterocyte cell model. SIGNIFICANCE AND IMPACT OF THE STUDY: This study
      indicates that Aeromonas strains carrying one or more virulence properties are
      prevalent in local waterways and are capable of translocating in a human
      enterocyte cell culture model. However, their importance in human
      gastrointestinal disease has yet to be verified under competitive conditions of
      the gut.

PMID- 16968310
TI  - Relative contribution of V-H+ATPase and NA+/H+ exchanger to bicarbonate
      reabsorption in proximal convoluted tubules of old rats.
AB  - With aging, the kidney develops a progressive deterioration of several structures
      and functions. Proximal tubular acidification is impaired in old rats with a
      decrease in the activity of brush border Na+/H+ exchange and a fall of H-ion flux
      measured with micropuncture experiments. In the present work we evaluate the
      contribution of 5-N-ethyl-n-isopropyl amiloride- (EIPA) and bafilomycin-sensitive
      bicarbonate flux (JHCO3-) in proximal convoluted tubules of young and aged rats.
      We performed micropuncture experiments inhibiting the Na+/H+ exchanger with EIPA
      (10(-4) M) and the V-H+ATPase with bafilomycin (10(-6) M). We used antibodies
      against the NHE3 isoform of the Na+/H+ exchanger and the subunit E of the V
      H+ATPase for detecting by Western blot the abundance of these proteins in brush
      border membrane vesicles from proximal convoluted tubules of young and old rats.
      The abundance of NHE3 and the V-H+ATPase was similar in 18-month-old and 3-month
      old rats. The bicarbonate flux in old rats was 30% lower than in young rats. EIPA
      reduced by 60% and bafilomycin by 30% in young rats; in contrast, EIPA reduced by
      approximately 40% and bafilomycin by approximately 50% in old rats. The inhibited
      by bafilomycin was the same in young and old rats: 0.62 nmol.cm-2.s-1 and 0.71
      nmol.cm-2.s-1, respectively. However, the EIPA-sensitive fraction was larger in
      young than in old rats: 1.26 nmol.cm-2.s-1 vs. 0.85 nmol.cm-2.s-1, respectively.
      These results suggest that the component more affected in bicarbonate
      reabsorption of proximal convoluted tubules from aged rats is the Na+-H+
      exchanger, probably a NHE isoform different from NHE3.

PMID- 16968311
TI  - New tricks of an old molecule: lifespan regulation by p53.
AB  - As guardian of the genome the tumor suppressor p53 controls a crucial point in
      protection from cellular damage and response to stressors. Activation of p53 can
      have beneficial (DNA repair) or detrimental (apoptosis) consequences for
      individual cells. In either case activation of p53 is thought to safeguard the
      organism at large from the deleterious effects of various stresses. Recent data
      suggest that the function of p53 might also play a role in the regulation of
      organismal lifespan. Increased p53 activity leads to lifespan shortening in mice,
      while apparent reduction of p53 activity in flies leads to lifespan extension.
      Although the mechanism by which p53 regulates lifespan remains to be determined,
      these findings highlight the possibility that careful manipulation of p53
      activity during adult life may result in beneficial effects on healthy lifespan.

PMID- 16968312
TI  - Guest editorial.

PMID- 16968313
TI  - Experiences and expectations of patients after oesophageal cancer surgery: an
      explorative study.
AB  - We investigated which problems patients experience after resection for
      oesophageal cancer and what care they expect, in order to devise a better
      tailored follow-up policy. Thirty patients, all within 1 year after surgery,
      filled in a one-time questionnaire on experienced physical, psychological and
      social problems and on expected care for these problems. Additionally, a semi
      structured interview was performed. Frequencies of experienced problems and
      expected care over time were analysed. The majority of patients experienced
      physical problems such as 'early satiety' (97%) and 'fatigue' (84%) after
      oesophagectomy. In addition, patients often felt depressed (64%), were afraid of
      metastases (80%) and death (47%). Over time, the frequency of problems such as
      'fatigue' (P = 0.035) and 'being dependent' (P = 0.012) decreased. Patients
      particularly expected professional care for physical issues related to their
      disease, whereas they often managed psychosocial problems in their own social
      network. Patients indicated that nurses' involvement during follow-up might
      improve their possibility to satisfactorily deal with problems. Patients
      frequently experience physical problems after oesophagectomy, and professional
      care is expected for these issues. Psychosocial problems are also present, but
      care is less commonly expected. Nurses' involvement during follow-up could be a
      way to optimize patients' management after oesophageal cancer surgery.

PMID- 16968314
TI  - The role of art-making in identity maintenance: case studies of people living
      with cancer.
AB  - The aim of this qualitative research was to understand why some people with
      cancer take up art as a leisure activity, and how visual art-making in daily life
      might support identity maintenance/reconstruction. The study forms part of a
      larger project with people who view art-making as a resource for living with
      chronic illness. In order to provide a detailed, holistic analysis, the paper
      focuses on the accounts and artwork of three participants, two women (aged 47 and
      59 years) each with breast cancer, and a man (aged 51 years) with stomach and
      lung cancer. The participants turned to art after a process of reflection but did
      not necessarily reject their pre-illness lifestyles or selves. Rather, art-making
      afforded many opportunities to retain familiar personal and social identities,
      and to resist being dominated by labels related to their illness. A practical
      implication is that people coping with cancer may need not only cognitive and
      emotional support, but opportunities to find meaningful activities. Such
      activities can be understood to have a powerful role in maintaining a familiar,
      positive identity in cancer, and providing a resource for coping.

PMID- 16968315
TI  - Reducing the risk of peripherally inserted central catheter line complications in
      the oncology setting.
AB  - At our institution, a retrospective review of peripherally inserted central
      catheters (PICCs) in oncology patients had previously demonstrated a complication
      rate of 40.7%. Since then we have implemented strategies to reduce complications
      including staff and patient education, insertion technique modification and PICC
      maintenance utilizing a PICC nurse. The objectives of this study were to evaluate
      the recent PICC complication rate and to compare it with the previously reported
      findings. Prospectively collected PICC complication data and medical records from
      all patients with solid tumours who had PICCs inserted in 2003 were analysed. A
      historical cohort comparative analysis was performed using our PICC complication
      rate from 2000 to 2001. Eighty-eight PICC lines were inserted in 73 patients
      under radiological guidance. The median PICC dwell time was 44 days (1-524 days).
      The overall complication rate was 15.9% (14/88) or 2.0 complications per 1,000
      PICC-days. Infections developed in 5.7% (5/88) and thrombotic events occurred in
      4.5% (4 /88) of PICCs. The mean time to complication was 45 days. The
      complication rate for 2003 was significantly lower than the rate for 2001 (P =
      0.006), especially of infective complications (P = 0.004). Strategies introduced
      to reduce PICC complications may have been the reason for this improvement.

PMID- 16968316
TI  - Staging practices of primary non-small-cell lung cancer: a literature review.
AB  - Lung cancer is the most frequent cause of cancer deaths worldwide, and non-small
      cell lung cancer (NSCLC) accounts for approximately 80% of all cases. Stage at
      diagnosis is the most important indicator of survival. Various non-invasive and
      invasive procedures are available for NSCLC staging. However, the precise
      indications for performing these procedures remain controversial. There is no
      evidence about the level of variability in practice of imaging and invasive
      procedures used for NSCLC staging. Their high costs contribute to the controversy
      about their use. We performed a literature search on the MEDLINE database to
      identify studies reporting practice of staging for a nonselected group of
      patients with NSCLC. Only seven studies enrolling between 185 and 2,071 patients
      reported NSCLC staging practices. These studies were reviewed to identify
      patterns in practice of staging work-up and consecutive treatment. Lack of
      detailed reporting limits the interpretation of the results. Based on our review,
      future investigations should be conducted to determine the extent of variation in
      patterns of physician practices of NSCLC staging and their impact on the
      treatment practice or patient survival.

PMID- 16968317
TI  - Family communication and mental health after breast cancer.
AB  - In the context of a traumatic event, such as a breast cancer diagnosis, talking
      with others about the event can facilitate emotional adjustment and meaning
      finding. Among women with a history of breast cancer, open communication is
      likely to be of particular importance in the family setting, as the family is
      frequently a primary source of support. The goal of this cross-sectional survey
      study was to determine the association between open family communication about
      cancer and breast cancer survivors' mental health. Responses from 230 women at
      various stages post-treatment suggest that the majority of women are able to talk
      openly with their family about breast cancer. Multivariate regression analysis
      further indicates that open family communication is independently associated with
      better mental health outcomes. Given that many women live long after a breast
      cancer diagnosis, maintaining mental health functioning is an important long-term
      goal. Efforts to enhance productive communication between patients and their
      family members may help women cope with and overcome the challenges of breast
      cancer survivorship.

PMID- 16968318
TI  - Gaining insight into the what, why and where of complementary and alternative
      medicine use by cancer patients and survivors.
AB  - The aim of this study was to gain a greater understanding of complementary and
      alternative medicine (CAM) use among cancer patients and survivors. Specific
      objectives included types used and timing, motivations for use and benefits
      received, sources of information on CAM and communication with doctors. Semi
      structured in-depth interviews were conducted with 19 patients and survivors
      (mean age = 57 years). Findings on frequency and type of CAM use were consistent
      with previous studies. Additionally, we found that the main expected benefit from
      using CAM was to boost the immune system, that participants could not readily
      explain the nature of the benefits they received, that CAM practitioners and
      books were the main sources of CAM information, and that the majority reported
      some discussion of CAM with a doctor. A greater range of questions needs to be
      asked of cancer patients in future quantitative studies. Reasons for commencing
      and stopping use of CAM and the quality of the CAM information source will be
      imperative to uncover, especially as the Internet is increasing in importance as
      a source for health information.

PMID- 16968319
TI  - Simultaneous pulmonary metastasectomy and hepatic radiofrequency ablation to
      treat recurrent metastases from rectal cancer.

PMID- 16968320
TI  - Is doctors' ability to identify cancer patients' worry and wish for information
      related to doctors' self-efficacy with regard to communicating about difficult
      matters?
AB  - The aims were to investigate whether: (A) doctors' ability to identify patients'
      worry about prognosis/wish for information about disease and treatment is related
      to doctors' self-efficacy with regard to communicating about difficult matters
      and patients' satisfaction with a consultation/hope to live a good life in spite
      of the disease; and (B) patients and doctors agree on how much worry/wish for
      information a patient experiences/wishes. Sixty-nine patients with carcinoid and
      11 doctors participated. Ability to identify worry/wish for information was
      estimated by posing questions to doctors/patients concerning how much
      worry/information a patient experienced/wished during a consultation. Doctors'
      self-efficacy was measured by nine questions, patients' satisfaction and hope by
      two questions. When doctors show good ability to identify wish for information,
      they report higher self-efficacy (t = 3.5, d.f. = 67, P < 0.001) than when they
      show less good ability. Patients finding the consultation very satisfying meet
      doctors reporting higher self-efficacy than patients finding the consultation
      satisfying (t = 2.26, d.f. = 65, P < 0.05). Doctors fail to identify patients who
      report less worry/wish more information than the average patient. The findings
      underscore the importance of further enhancing doctors' self-efficacy with regard
      to communicating about difficult matters and ability to identify patients who are
      less worried/wish more information than the average patient.

PMID- 16968321
TI  - Cost of illness of malignant lymphoma in Germany.
AB  - Cancer causes a high economic burden. The purpose of this study is to determine
      and compare the direct, indirect and societal costs of illness for Hodgkin's
      Disease (HD), Non-Hodgkin's Lymphoma (NHL), Plasmocytoma and Chronic Lymphatic
      Lymphoma (CLL). We used a database of 1.9 million individuals enrolled in a
      statutory sickness fund in Germany to identify 4,172 patients treated for
      malignant lymphoma in 2000. Direct, indirect and societal costs were calculated
      using a case-control design and the human capital approach. Direct cost (in Euro)
      for patients with HD was 3604, for NHL patients 6,149, for Plasmocytoma 8,400,
      and for CLL patients 3,226. Total indirect cost for HD was 69 million, for NHL
      patients 404 million, for Plasmocytoma 144 million, and for CLL patients 52
      million. Totalling 1.7 billion Euro in economic cost for Germany in 2000, with
      44,000 productive years lost, malignant lymphomas are a relatively costly disease
      group. As life expectancy increases, costs for malignant lymphoma are likely to
      rise due to the high prevalence among the elderly. Further research employing
      disaggregated, incidence-based cost is needed.

PMID- 16968322
TI  - Feasibility of an exercise rehabilitation programme for cancer patients.
AB  - A growing body of evidence indicates the benefits of exercise as a rehabilitation
      intervention for cancer patients. However, few hospitals offer exercise-based
      rehabilitation programmes to patients. This study evaluated the feasibility and
      acceptability of a group-based exercise programme for cancer patients attending a
      local oncology centre. The intervention consisted of a weekly instructor-led
      circuit training class supplemented by home-based activity 4 days/week for 10
      weeks. From 28 eligible patients, 12 were recruited (43%), of whom nine completed
      the intervention (75%). The three withdrawals were due to worsening of disease.
      Adherence (mean of 7.5 classes attended and 4 days/week of home activity
      performed) and tolerability (no adverse events) were good. Positive features of
      the programme identified in interviews with participants included the variety and
      scope of the exercises, and the empathetic but positive approach of the
      instructors. The small group format was highly valued with participants receiving
      social support and inspiration from each other. Perceived outcomes included
      improved fitness, reduced fatigue, enjoyment, enhanced mood and a sense of
      achievement. Several participants felt that the intervention represented a
      stepping stone to becoming habitual exercisers. Results suggested that the
      programme was feasible and acceptable to patients, but uptake was low, indicating
      a need for more effective recruitment strategies in order for a cost-effective
      service to be implemented.

PMID- 16968323
TI  - Traditional Chinese medicine in cancer care: perspectives and experiences of
      patients and professionals in China.
AB  - Although traditional Chinese medicine (TCM) is widely used in Chinese cancer
      centres, it is a brand new area for formal scientific evaluation. As the first
      step of developing a research programme on clinical evaluation of TCM for cancer
      patients, we conducted a qualitative study to explore the perspectives and
      experiences of Chinese cancer patients and TCM professionals. Twenty-eight
      persons participated in two cancer patient focus groups and one professional
      focus group. Semi-structured interviews were audiotaped, transcribed and
      translated. Textual transcripts and field notes underwent inductive thematic
      analysis. We found that patients' decision to use TCM for cancer is a self-help
      process with a deep cultural grounding, which is related to the traditional
      Chinese philosophy of life. Participants perceived TCM to be an effective and
      harmless therapy. They highly valued the fact that TCM is tailored to patients,
      and believed it was the basis of an optimal and safe treatment. Participants also
      highlighted the long-term positive effects, the benefit of group interventions
      and the low cost as important features of TCM. Subjects believed that conducting
      clinical research would be crucial for the recognition and dissemination of TCM
      in Western countries. The findings of this study are expected to contribute to
      the knowledge base on the current TCM use for cancer in China, and to provide
      useful information for developing future clinical research in this area in
      Western countries.

PMID- 16968326
TI  - Soluble CD40 ligand in asthma patients during allergen challenge.

PMID- 16968327
TI  - Chewing fails to induce oral bacteraemia in patients with periodontal disease.
AB  - AIM: To investigate whether chewing in patients with untreated chronic
      periodontitis or plaque-induced gingivitis causes bacteraemia of oral origin.
      METHOD: Twenty-one patients with untreated chronic periodontitis (32-75 years
      old) and 20 with plaque-induced gingivitis (26-54 years old) chewed a standard
      wax medium for 4 min. Blood samples were drawn before, during and 5 min. post
      chewing. Aerobic and anaerobic Bactec system culturing was performed for 21 days
      and positive bottles were subcultured and isolates were identified to genus
      level. A full periodontal analysis was performed on all teeth and included
      probing depths, recession, attachment levels, bleeding on probing, mobility
      plaque index and gingival index. Radiographs were assessed for the severity of
      alveolar bone loss. RESULTS: No bacteraemia of oral origin was detected in any
      patient. Skin contaminants (Staphylococcus epidermidis, Propionibacterium spp.)
      were detected in blood samples from three patients (two periodontitis; one
      gingivitis). CONCLUSION: Chewing did not cause bacteraemia in chronic
      periodontitis or plaque-induced gingivitis patients and may not be a risk factor
      for infective endocarditis in at-risk individuals with periodontal disease.

PMID- 16968328
TI  - Tackling the diabetic platelet: is high clopidogrel dosing the answer?

PMID- 16968329
TI  - Acute activation of the endothelium results in increased levels of active von
      Willebrand factor in hemolysis, elevated liver enzymes and low platelets (HELLP)
      syndrome.
AB  - BACKGROUND: HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome
      is a severe complication of pre-eclampsia in pregnancy, characterized by
      microvascular platelet thrombi. Activation of the endothelium is thought to play
      a key role in pre-eclampsia and HELLP syndrome. Activation of endothelial cells
      may lead to release of von Willebrand factor (VWF) multimers, which are highly
      reactive with platelets. Normally, newly released multimers are cleaved by
      ADAMTS13, resulting in less reactive derivatives. OBJECTIVE: We hypothesized that
      HELLP syndrome is characterized by increased amounts of active VWF compared with
      healthy pregnancy and pre-eclampsia, due to acute activation of endothelial
      cells. This might contribute to thrombocytopenia and thrombotic microangiopathy.
      METHODS: Active VWF and ADAMTS13 activity were measured in healthy pregnant
      volunteers (n = 9), patients with pre-eclampsia (n = 6) and patients with HELLP
      syndrome (n = 14) at similar gestational ages. To study the role of endothelial
      cell activation, the propeptide/mature VWF ratio was determined, and VWF released
      by cultured endothelial cells was analyzed. RESULTS: Active VWF levels were
      increased 2.1-fold in HELLP syndrome compared with healthy pregnant volunteers (P
      < 0.001) and 1.6-fold compared with patients with pre-eclampsia (P = 0.001).
      ADAMTS13 activity was moderately decreased in patients with HELLP syndrome
      compared with healthy pregnant volunteers (P < 0.004), but not compared with
      patients with pre-eclampsia. The propeptide/mature VWF ratio was increased 1.7
      fold compared with healthy pregnant volunteers (P < 0.001) and 1.5-fold compared
      with patients with pre-eclampsia (P < 0.05). A significant correlation was found
      between this ratio and the activation factor of VWF (r = 0.68, P < 0.001). The
      amount of active VWF was increased 1.4-fold in medium of stimulated endothelial
      cells when compared with non-stimulated cells (P < 0.05). CONCLUSION: Acute
      endothelial cell activation in HELLP syndrome and decreased ADAMTS13 activity
      result in increased amounts of active VWF. This might explain the consumptive
      thrombocytopenia and thrombotic microangiopathy associated with HELLP syndrome.
      Inhibition of circulating active VWF could be a potential new approach in the
      treatment of patients with HELLP syndrome.

PMID- 16968330
TI  - Use of preventive measures for air travel-related venous thrombosis in
      professionals who attend medical conferences.
AB  - BACKGROUND: Lack of guidelines for prevention of air travel-related venous
      thrombosis may lead to excessive use of potentially dangerous precautions.
      OBJECTIVES: To assess the use of preventive measures for air travel-related
      thrombosis in professionals employed in the field of thrombosis and hemostasis
      and in other fields. METHODS: A survey amongst delegates of the XXth ISTH
      Congress, the 15th ISDB Congress and the 13th Cochrane Colloquium, which all took
      place in Australia 2005. RESULTS: Two thousand and eighty-nine questionnaires
      were completed (response 53%). Overall, 80% of the respondents had used
      preventive measures. Low-molecular-weight heparin and vitamin K antagonists were
      mostly used by ISTH delegates (10% vs. 1% at the other conferences). Medical
      doctors used more pharmacological prophylaxis (31%) than research fellows (11%)
      and non-clinical scientists (22%). Dutch (64%) and Asian respondents (67%) least
      used any prevention, whereas Israeli used most (94%). Subjects with risk factors
      for thrombosis more often used prophylaxis (90%) than those without (77%). In a
      multivariate analysis, conference, nationality, age, presence of risk factors and
      profession were determinants of prophylaxis use. CONCLUSION: Major differences in
      the use of prophylactic measures for air travel-related thrombosis stress the
      need for studies of interventions and clear guidelines on prevention of air
      travel-related venous thrombosis.

PMID- 16968331
TI  - Vascular endothelial growth factor expression in monocytes from patients with
      primary antiphospholipid syndrome.
AB  - BACKGROUND: One of the described mechanisms leading to thrombosis in
      antiphospholipid syndrome (APS) is overexpression of tissue factor (TF) in the
      monocytes and endothelial cells of patients with antiphospholipid antibodies
      (aPL). Vascular endothelial growth factor (VEGF) may stimulate monocyte TF
      expression through its receptor, the tyrosine kinase Flt-1. OBJECTIVES: This
      study aimed to analyze the following in monocytes of 55 primary APS patients:
      VEGF and Flt-1 expression levels, their potential regulation by aPL, and the
      association of VEGF and Flt-1 expression with the increased TF expression found
      in APS patients. RESULTS: Purified monocytes from APS patients showed higher
      levels of VEGF and Flt-1 than healthy donors, which further correlated with
      immunoglobulin G (IgG) anticardiolipin titers and TF expression rank. Moreover,
      monocyte VEGF and Flt-1 levels were significantly higher in patients with than in
      patients without previous thrombosis. In vitro, IgG from APS patients increased
      monocyte VEGF and Flt-1 expression in a dose-dependent manner. VEGF and Flt-1
      expression was significantly inhibited by the p38 mitogen-activated protein
      kinase (MAPK) inhibitor SB203580; this suggests the involvement of this kinase in
      the aPL-induced VEGF and Flt-1 upregulation. CONCLUSIONS: Our data show, for the
      first time in vivo, that monocytes from primary APS patients have an increased
      expression of VEGF and Flt-1. Furthermore, in vitro results indicated that this
      cytokine is produced by monocytes when treated with aPL, and that the p38 MAPK
      signaling pathway plays an important role. Thus, VEGF might act as a regulatory
      factor in aPL-mediated monocyte activation and TF expression, thereby
      contributing to the proinflammatory-prothrombotic phenotype of APS patients.

PMID- 16968332
TI  - Diageo, University College Dublin and the integrity of alcohol science: It's time
      to draw the line between public health and public relations.

PMID- 16968333
TI  - Sickness absence as an alcohol-related problem.

PMID- 16968334
TI  - Cannabis use, depression and public health.

PMID- 16968335
TI  - Are books a thing of the past for the development of addiction science?

PMID- 16968336
TI  - Public injecting and the need for 'safer environment interventions' in the
      reduction of drug-related harm.
AB  - BACKGROUND: One key structural dimension in the distribution of drug-related harm
      associated with injecting drug use is the injecting environment. Epidemiological
      evidence associates elevated blood-borne viral risk with injecting in 'public'
      and 'semipublic' environments. Yet the quality of evidence on public injecting
      and related viral risk is variable, and is lacking in many countries such as the
      United Kingdom. AIM: This commentary considers the micro-injecting environment as
      a critical dimension of risk, exploring the need for 'safer injecting environment
      interventions'. METHODS: We draw upon published research evidence and qualitative
      case examples. RESULTS: We note the limits in epidemiological evidence on public
      injecting and emphasize the need for ethnographic research to determine the
      'social relations' of how drug users and risk practices interact with injecting
      environments. We identify three main forms of 'safer environment intervention':
      purpose-built drug consumption rooms; interventions within existing spatial
      relations; and spatial programming and urban design. While drug consumption rooms
      find evidence-based support, they are not a panacea. We emphasize the potential
      of interventions embedded within existing spatial and social relations. These
      include low-cost pragmatic interventions enhancing facilities and safety at
      public and semipublic injecting sites and, primarily, peer-based interventions,
      including peer-supervised injecting sites. We caution against spatial programming
      and urban design interventions which can cause the displacement of socially
      marginalized populations and the redistribution of harm. CONCLUSIONS: Public
      health interventions in the addictions field have in the past focused upon
      individual behavioural change at the cost of social interventions and
      environmental change. We wish to focus greater attention on reducing risks
      related to public injecting and encourage greater debate on 'safer environment
      interventions' in harm reduction.

PMID- 16968337
TI  - The ability of two commercially available quick test kits to detect drug
      facilitated sexual assault drugs in beverages--a response by Bloomsbury
      Innovations Ltd.

PMID- 16968339
TI  - Alcohol use in the country with the world's highest per capita beer consumption-
      the Czech Republic.

PMID- 16968340
TI  - Conversation with Juha Partanen.

PMID- 16968341
TI  - Ethyl glucuronide in hair: Is it a reliable marker of chronic high levels of
      alcohol consumption?
AB  - AIMS: This study aims to investigate the relationship between ethanol daily
      intake (EDI) and the levels of ethyl glucuronide in hair. DESIGN: Ethyl
      glucuronide concentration was determined in hair samples from different classes
      of ethanol drinkers and results were compared with the reported information about
      drinking habits. SETTING: Pavia, Italy. PARTICIPANTS: Twenty-two known
      alcoholics, 21 volunteers self-reporting an EDI from 2 to 60 g, and seven
      teetotallers were involved in this study. MEASUREMENTS: Ethyl glucuronide
      determination in hair samples was performed by liquid chromatography-tandem mass
      spectrometry (limit of detection: 2 pg/mg, lower limit of quantification: 3
      pg/mg). FINDINGS: Current known alcoholics (n = 21) had ethyl glucuronide hair
      concentration in the range 4.0-434.7 pg/mg (average: 62.8, median 37.4 pg/mg);
      ethyl glucuronide was not detected in hair samples from teetotallers (n = 7); all
      volunteers reporting an EDI of at least 30 g ('non-moderate drinkers' according
      to the US Department of Health and Human Services) tested positive for ethyl
      glucuronide (cut-off: 4 pg/mg). All volunteers declaring an ethanol daily intake
      higher than 40 g ('heavy drinkers' according to the World Health Organization,
      Regional Committee for Europe) tested positive for this compound (cut-off: 5
      pg/mg). The application of a cut-off of either 4 pg/mg or 5 pg/mg resulted in one
      false positive, coming from a volunteer asserting an ethanol daily intake of 30
      g. No false negatives were found. CONCLUSIONS: The concentration of ethyl
      glucuronide in hair appears to correlate with EDI.

PMID- 16968342
TI  - The ability of two commercially available quick test kits to detect drug
      facilitated sexual assault drugs in beverages.
AB  - AIMS: Assessment of the sensitivity and specificity of two commercially available
      'drug-facilitated sexual assault' drug detector kits, Drink Guard and Drink
      Detective. DESIGN: Experimental. SETTING: Laboratory. MEASUREMENTS: Gamma
      hydroxybutyrate (GHB) sodium salt, ketamine hydrochloride, temazepam,
      flunitrazepam and diazepam were dissolved (Tween added to benzodiazepine
      solutions) as separate stock solutions and added to 330 ml samples of cola (Pepsi
      Max), beer (Stella Artois), 'alcopop' (Bacardi Breezer) and placebo (distilled
      water). The doses used are reported to be common in cases of intoxication. Each
      kit was tested 10 times for each drink/drug combination. Two blind, independent
      observers scored each test (presence/absence of drug) in accordance with kit
      instructions; chi 2 was used to compare the proportion of times raters scored
      tests correctly and incorrectly. Sensitivity and specificity were calculated
      overall, for each drink, and sensitivity was calculated for each drug. Inter
      observer agreement was evaluated using the kappa statistic. FINDINGS: While both
      raters were able to score significantly more tests correctly than incorrectly
      using Drink Detective, and one rater scored similarly using Drink Guard, the
      overall sensitivity of Drink Detective and Drink Guard was 69.0% (95% CI 64.2
      73.5%) and 37.5% (95% CI 30.1-45.5%), respectively. Sensitivity was drink
      dependent. Drink Detective was unable to detect our dose of GHB in water, with
      all tests scored negatively by both raters for this drink/drug combination (n =
      20 negative scores). Overall, specificity was 76.6% (95% CI 71.5-81.0%) and 87.9%
      (95% CI 83.0-91.6%) for Drink Guard and Drink Detective, respectively, but was
      affected by the beverage. Inter-rater agreement was poor for Drink Guard (kappa =
      0.278 +/- 0.069) but excellent for Drink Detective (kappa = 0.894 +/- 0.245).
      Inter-observer agreement was drug-dependent. CONCLUSIONS: Use of drug detector
      kits by the public in the night-time environment needs further investigation and
      may create a false sense of security (false negatives) and undue concern (false
      positives) among kit users.

PMID- 16968343
TI  - Per capita alcohol consumption and sickness absence.
AB  - AIM: The purpose of the study was to assess the relationship between aggregate
      alcohol consumption and sickness absence in Sweden. DATA AND METHODS: Two
      indicators of sickness absence were used, one based on sickness insurance data,
      the other on data from the labour force surveys. Alcohol consumption was gauged
      by sales of pure alcohol (100%) per inhabitant 15 years of age and older. Because
      changes in the economy may affect alcohol consumption as well as sickness
      absence, two macroeconomic indicators were included as control variables:
      unemployment and real wages. The study period was 1935-2002. The data were
      analysed through the Box-Jenkins method for time-series analyses. FINDINGS: A 1
      litre increase in total consumption was associated with a 13% increase in
      sickness absence among men (P < 0.05). The relationship was not statistically
      significant for women. CONCLUSIONS: Previous research has documented that
      aggregate alcohol consumption is related to a large number of harm indicators,
      such as cirrhosis and accident mortality. The present findings add yet another
      indicator to this list.

PMID- 16968344
TI  - How many drinks does it take you to feel drunk? Trends and predictors for
      subjective drunkenness.
AB  - AIMS: To describe and model the sources of the variation and trends in the
      meaning of subjective drunkenness. DESIGN: Trend analyses of three cross
      sectional surveys. SETTING: US general population. PARTICIPANTS: Those who report
      being drunk in the past year among those in the 1979, 1995 and 2000 National
      Alcohol Surveys. MEASUREMENTS: Number of drinks reported to feel drunk (dependent
      variable), past-year alcohol consumption measures, beverage preference, state
      drunk driving blood alcohol concentration (BAC) limit and demographics. FINDINGS:
      The mean reported number of drinks to feel drunk declined significantly between
      each survey and was significantly lower for women. Considerable variation was
      also found within surveys and was explained partially by available variables.
      Volume of alcohol and heavy drinking occasions were associated positively with
      the number of drinks to feel drunk. Higher educational attainment was associated
      negatively as was being a wine drinker, of older age, of African American
      ethnicity and of becoming drunk more frequently than once per month. Living in a
      state with a per se BAC limit of 0.08% was associated negatively in models for
      men. CONCLUSIONS: A substantial shift downward in the meaning of drunkenness
      occurred in the US between 1979 and 2000. This may be explained partly by the
      increase in educational attainment, the ageing of the population, the decline in
      per capita alcohol consumption and changes in alcohol policy towards lower BAC
      limits for drunk driving along with greater penalties, enforcement and awareness.

PMID- 16968345
TI  - Alcohol dependence in relation to burnout among the Finnish working population.
AB  - AIMS: To investigate the relationship of burnout to alcohol dependence and high
      alcohol consumption. DESIGN: A cross-sectional population-based multi
      disciplinary 'Health 2000 Study'. The analyses were performed separately for the
      women and the men and adjusted for socio-demographic factors. SETTING AND
      PARTICIPANTS: In Finland, 3276 active employees (1637 women and 1639 men), aged
      30-64 years, from a representative population sample. MEASUREMENTS: The diagnosis
      of Diagnostic and Statistical Manual of Mental Disorders version IV (DSM-IV)
      alcohol dependence was based on the standardized Munich Composite International
      Diagnostic Interview (M-CIDI). The assessment of high alcohol consumption was
      based on self-reported alcohol use. Burnout was assessed with the Maslach Burnout
      Inventory-General Survey (MBI-GS). FINDINGS: The 12-month prevalence of alcohol
      dependence was associated with burnout among both men and women. Each one-point
      increase in burnout score was associated with an 80% increase in the incidence
      for alcohol dependence among women and a 51% increase among men. These
      associations persisted when socio-demographic factors were adjusted. The
      associations between burnout and high alcohol consumption were not statistically
      significant. CONCLUSIONS: There is an association between burnout and alcohol
      dependence among both genders. Among both women and men, attention to alcohol
      related behaviour is warranted in the clinical context when burnout and other
      problems related to work are encountered. Interventions which include assessment
      of work conditions and management of work-related stress should be targeted at
      employees with alcohol dependence in addition to traditional treatment.

PMID- 16968346
TI  - Becker's rational addiction theory: An empirical test with price elasticities for
      distilled spirits in Denmark 1911-31.
AB  - AIM: To test an implication of Becker's rational addiction theory, namely that
      price changes will lead both to simultaneous consumption changes as well as
      lagged changes (and potentially also immediate changes if future changes in
      prices are anticipated). DESIGN: Time-series analysis, first of aggregate sales
      of distilled spirits and prices, controlled for gross national product (GNP), and
      secondly of deaths from delirium tremens. SETTING: Denmark 1911-31. Price changes
      were very large in the period 1916-18 due to shortages during World War I, and
      the Danish case can be conceived as a natural experiment. FINDINGS: No evidence
      for lagged price effects in the expected direction was found. On the contrary,
      the evidence pointed in the opposite direction. The immediate reduction in sales
      following rising prices are, to some degree, counteracted by an adjustment in the
      opposite direction the following year. The delirium tremens data confirm this
      pattern. CONCLUSION: Becker's theory is not confirmed. Several possible
      explanations are discussed. If the pattern observed in these data is
      representative of a more general mechanism, current price elasticity estimates
      may be too high, by ignoring lagged compensatory effects.

PMID- 16968347
TI  - Naltrexone versus acamprosate in the treatment of alcohol dependence: A multi
      centre, randomized, double-blind, placebo-controlled trial.
AB  - AIM: To compare the efficacy of acamprosate and naltrexone in the treatment of
      alcohol dependence. DESIGN: A double-blind, placebo-controlled trial. SETTING:
      Three treatment centres in Australia. PARTICIPANTS: A total of 169 alcohol
      dependent subjects were given naltrexone (50 mg/day), acamprosate (1998 mg/day)
      or placebo for 12 weeks. INTERVENTION: All subjects were offered manualized
      compliance therapy, a brief intervention that targets problems that may affect
      treatment compliance such as ambivalence and misperceptions about medication.
      MEASUREMENTS: Time to the first drink, time to first relapse, drinks per drinking
      day and cumulative abstinence. FINDINGS: In intention-to-treat analyses, there
      were no differences between groups on outcome measures of drinking, craving or
      biochemical markers. Similarly, analyses of the 94 subjects that completed the
      study in full and demonstrated 80% compliance, revealed no significant treatment
      effects. Differential treatment effects were identified after stratification
      according to scores on the Alcohol Dependence Scale (ADS) and Depression Anxiety
      and Stress Scale (DASS). A significant beneficial treatment effect on time to
      first relapse was revealed for subjects with 'no depression' allocated to
      naltrexone (n = 56; P < 0.01). In addition, a significant beneficial treatment
      effect was revealed in subjects with 'low dependence' allocated to naltrexone (n
      = 34; P < 0.05). CONCLUSIONS: The results of this study support the efficacy of
      naltrexone in the relapse prevention of alcoholism amongst those with low levels
      of clinical depression and alcohol dependence severity. No effect of acamprosate
      was found in our sample.

PMID- 16968348
TI  - Marijuana use and depression among adults: Testing for causal associations.
AB  - AIM: To determine whether marijuana use predicts later development of depression
      after accounting for differences between users and non-users of marijuana.
      DESIGN: An ongoing longitudinal survey of 12 686 men and women beginning in 1979.
      SETTING: The National Longitudinal Survey of Youth of 1979, a nationally
      representative sample from the United States. PARTICIPANTS: A total of 8759
      adults (age range 29-37 years) interviewed in 1994 had complete data on past-year
      marijuana use and current depression. MEASUREMENTS: Self-reported past-year
      marijuana use was tested as an independent predictor of later adult depression
      using the Center for Epidemiologic Studies-Depression questionnaire. Individual's
      propensity to use marijuana was calculated using over 50 baseline covariates.
      FINDINGS: Before adjusting for group differences, the odds of current depression
      among past-year marijuana users is 1.4 times higher (95% CI: 1.1, 1.9) than the
      odds of depression among the non-using comparison group. After adjustment, the
      odds of current depression among past-year marijuana users is only 1.1 times
      higher than the comparison group (95% CI: 0.8, 1.7). Similarly, adjustment
      eliminates significant associations between marijuana use and depression in four
      additional analyses: heavy marijuana use as the risk factor, stratifying by
      either gender or age, and using a 4-year lag-time between marijuana use and
      depression. CONCLUSIONS: After adjusting for differences in baseline risk factors
      of marijuana use and depression, past-year marijuana use does not significantly
      predict later development of depression. These findings are discussed in terms of
      their relevance for understanding possible causal effects of marijuana use on
      depression.

PMID- 16968349
TI  - The prevalence of psychotic symptoms among methamphetamine users.
AB  - AIMS: To examine the prevalence of psychotic symptoms among regular
      methamphetamine users. DESIGN: Cross-sectional survey. SETTING: Participants were
      recruited from Sydney, Australia, through advertisements in free-press magazines,
      flyers and through word-of-mouth. PARTICIPANTS: Methamphetamine users (n = 309)
      who were aged 16 years or over and took the drug at least monthly during the past
      year. MEASUREMENTS: A structured face-to-face interview was used to assess drug
      use, demographics and symptoms of psychosis in the past year. Measures of
      psychosis included: (a) a psychosis screening instrument derived from the
      Composite International Diagnostic Interview; and (b) the Brief Psychiatric
      Rating Scale subscales of suspiciousness, unusual thought content, and
      hallucinations. Dependence on methamphetamine was measured using the Severity of
      Dependence Scale. FINDINGS: Thirteen per cent of participants screened positive
      for psychosis, and 23% had experienced a clinically significant symptom of
      suspiciousness, unusual thought content or hallucinations in the past year.
      Dependent methamphetamine users were three times more likely to have experienced
      psychotic symptoms than their non-dependent counterparts, even after adjusting
      for history of schizophrenia and other psychotic disorders. CONCLUSION: The
      prevalence of psychosis among the current sample of methamphetamine users was 11
      times higher than among the general population in Australia. Dependent
      methamphetamine users are a particularly high-risk group for psychosis.

PMID- 16968350
TI  - A randomized controlled pilot study of motivational interviewing for patients
      with psychotic and drug use disorders.
AB  - AIMS: This pilot study examined the efficacy of a two-session motivational
      interview adapted for dually diagnosed psychotic and drug-related disordered
      patients (DDMI) in comparison to a two-session standard psychiatric interview
      (SI). DESIGN: The study used a randomized controlled trial design. Participants
      received either DDMI or SI and were assessed at baseline, 4-, 8- and 12-week
      follow-up points. The principal analysis for examination of treatment effects
      across time was a random effects regression model. SETTING: Both DDMI and SI
      interviews served as pre-admission intake interventions to an ambulatory
      specialty dual diagnosis intensive out-patient and partial hospital program.
      PARTICIPANTS: Forty-four treatment-seeking participants (DDMI = 24; SI = 20) who
      had co-occurring psychotic and drug-related disorders were assigned randomly to
      the treatment conditions. Measurements Primary outcomes were days of primary drug
      use, secondary drug use, alcohol use and psychotropic medication adherence,
      proportion of participants admitted into the program and days of attendance.
      FINDINGS AND CONCLUSIONS: DDMI and SI resulted in improved treatment outcomes,
      but there were no main effects for the sample as a whole. Separate examination of
      primary cocaine and primary marijuana using subsamples, however, suggested that
      DDMI resulted in significantly better primary drug treatment outcomes for the
      cocaine-using group, whereas SI resulted in significantly better primary drug
      treatment outcomes for the marijuana-using group. These findings indicate that MI
      may not work equally well for all types of psychotic disordered dually diagnosed
      patients and that alternative approaches may be as effective in fostering
      improved substance use treatment outcomes for subgroups of these individuals.

PMID- 16968351
TI  - HIV prevalence among injection drug users in rural Guangxi China.
AB  - AIMS: To determine the HIV-1 seroprevalence, risk behaviors and demographic
      characteristics associated with HIV-1 infection among injection drug users (IDU)
      in rural Guangxi, China. DESIGN AND SETTING: Between July and November 2002, 702
      IDU were screened for HIV-1 antibody through community outreach in rural Guangxi,
      China for enrollment in an HIV sero-incidence study. PARTICIPANTS: A total of 702
      active high-risk IDU were screened. High-risk injection was defined as anyone who
      reported injecting drugs at least three times per week in the last month or
      injected drugs with shared equipment on at least three occasions in the last 3
      months. MEASUREMENTS: HIV-1 antibody testing with confirmation by Western blot
      was performed on all subjects. Demographic and risk assessment survey data were
      collected at screening from everyone whose baseline HIV antibody status was
      known. FINDINGS: HIV-1 antibody prevalence among 702 IDU at baseline was 25% with
      a median age of 26.7 years (18.2-43.2). Based on a multivariate logistic
      regression model using risk factors identified in univariate analyses, the
      following risk factors were associated significantly with an increase in risk for
      HIV seropositivity: age > 26 years (OR 1.50; 95% CI 1.04, 2.17), sharing of rinse
      water (OR = 1.24; 95% CI 1.09, 1.40), not having sex in the last 6 months (OR =
      1.62; 95% CI 1.08, 2.43). CONCLUSIONS: HIV infection among IDU in Guangxi, one of
      China's major HIV epidemic regions, is high and the infection occurs
      predominantly among older IDU males who share rinse water.

PMID- 16968352
TI  - Incidence and risk factors for hepatitis C seroconversion in injecting drug users
      in Australia.
AB  - AIMS: To determine the incidence of hepatitis C virus (HCV) infection and
      identify risk factors for seroconversion. DESIGN: Prospective cohort study.
      Participants were recruited through direct approaches, street-based outreach,
      methadone and sexual health clinics and needle and syringe programmes. SETTING:
      Urban, regional and rural settings in New South Wales, Australia. PARTICIPANTS:
      Injecting drug users (IDUs) (n = 584) were screened and tested for exposure to
      HCV. Between 1999 and 2002 antibody HCV negative IDUs (n = 368) were enrolled and
      followed-up every 3-6 months until seroconversion or study completion.
      MEASUREMENTS: Interviewer-administered baseline and follow-up questionnaires
      consisted of 131 items and included demographics, drug use and risk behaviour.
      Approximately 10 cc of whole blood was drawn at each visit. Specimens were stored
      at -70C and serology performed using one or two third-generation enzyme-linked
      immunosorbent assays and polymerase chain reaction testing. FINDINGS: Sixty-eight
      seroconversions were observed and incidence was 30.8 per 100 person-years, with
      incidence in IDUs injecting < 1 year, 133 per 100 person-years. Independent
      predictors of seroconversion were female gender, duration of injecting, injecting
      cocaine, shared use of filters and recruitment strategy. CONCLUSIONS: Women, new
      initiates and IDUs recruited via outreach appear to be at increased risk of
      infection. Results confirm the significance of cocaine injection as a risk factor
      and provide the first evidence outside North America of the link between shared
      use of drug preparation equipment and incident HCV infection. Prevention efforts
      should attempt to raise awareness of the risks associated with drug sharing and,
      in particular, the role of potentially contaminated syringes in HCV infection.

PMID- 16968354
TI  - Smoking reduction and biomarkers in two longitudinal studies.
AB  - AIMS: To measure reduction in exposure to smoke in two population-based studies
      of self-reported smoking reduction not using nicotine replacement. DESIGN: Cross
      sectional analyses of biomarkers and smoking. SETTING: Data from two time-points
      in the Copenhagen City Heart Study (CCHS), 1981/83 and 1991/94, and the
      Copenhagen Male Study (CMS) in 1976 and 1985/86, respectively. PARTICIPANTS:
      There were 3026 adults who were smokers at both time-points in the CCHS and 1319
      men smoking at both time-points in the CMS. MEASUREMENTS: Smoking status and
      tobacco consumption were assessed by self-completion questionnaire. Measurements
      of biomarkers of smoke intake were taken at the second time-point in the two
      studies: expired-air carbon monoxide (CO) in the CCHS and serum cotinine in the
      CMS. Biomarker levels in medium (15-29 g tobacco/day) and heavy (> 30 g/day)
      smokers at the first time-point who later reported a reduction in cigarettes per
      day of 50% or more without quitting were compared with continuing medium, heavy
      and light smokers (1-14 g/day) using linear regression. Sex (CCHS only), age,
      self-reported inhalation of smoke, duration of smoking, type of tobacco and
      amount smoked were included as covariates in multivariate models. FINDINGS: Heavy
      smokers who reduced did not show lower levels of biomarkers at follow-up. Medium
      smokers who reduced showed a reduction in cotinine but not CO. The reduction in
      cotinine was not commensurate with the reported reduction in consumption.
      CONCLUSIONS: Long-term reductions in self-reported tobacco smoking are probably
      associated with, at best, modest reductions in smoke exposure.

PMID- 16968353
TI  - Cigarettes and oral snuff use in Sweden: Prevalence and transitions.
AB  - AIMS: To investigate the prevalence and patterns of transitions between cigarette
      and snus use. DESIGN: Cross-sectional study within the population-based Swedish
      Twin Registry. SETTING AND PARTICIPANTS: A total of 31 213 male and female twins
      42-64 years old. MEASUREMENTS: Age-adjusted prevalence odds ratios (POR) and 95%
      confidence intervals (CIs) described the association between gender and tobacco
      use, while Kaplan-Meier survival methods produced cumulative incidence curves of
      age at onset of tobacco use. Life-time tobacco use histories were constructed
      using ages at onset of tobacco use and current tobacco use status. FINDINGS:
      Although more males reported ever smoking (64.4%) than females (61.7%), more
      males were former smokers (POR: 1.33, 95% CI: 1.27-1.39). Males were far more
      likely to use snus than females (POR: 18.0, 95% CI: 16.17-20.04). Age at onset of
      cigarette smoking occurred almost entirely before age 25, while the age at onset
      of snus use among males occurred over a longer time period. Most men began using
      cigarettes first, nearly one-third of whom switched to using cigarettes and snus
      in combination. While 30.6% of these combined users quit tobacco completely, only
      7.4% quit snus and currently use cigarettes, while 47.7% quit cigarettes and
      currently use snus. CONCLUSIONS: Current cigarette smoking is more prevalent
      among Swedish women than men, while snus use is more prevalent among men. Among
      men who reported using both cigarettes and snus during their life-time, it was
      more common to quit cigarettes and currently use snus than to quit snus and
      currently use cigarettes. Once snus use was initiated, more men continued using
      snus rather than quit tobacco completely.

PMID- 16968355
TI  - Mortality in a cohort of opiate and amphetamine users in Perth, Western
      australia: Comment on Bartu et al. (2006).

PMID- 16968358
TI  - Editorial.

PMID- 16968359
TI  - Psychiatry in selected countries of Central and Eastern Europe: an overview of
      the current situation.
AB  - OBJECTIVE: To review the current status of psychiatry in selected countries of
      Central and Eastern Europe: Bulgaria, Croatia, Czech Republic, Hungary, Poland,
      Romania, Russia, Slovakia, and Slovenia. METHOD: A group of psychiatrists from
      the region evaluated the status of psychiatry at the end of 2004 based on data
      from their countries and information available on WHO homepages. RESULTS: There
      is a shift from traditional in-patient facilities towards out-patient and
      community services as evidenced by a decreasing number of hospital beds. Economic
      pressures affect the financing of psychiatric services, and reimbursement for
      novel psychotropics. Political changes were followed by updated legislation.
      Psychiatric training, pre-, postgraduate and continuous medical education, are
      gradually being transformed. Scientific output as measured by publications in
      peer-reviewed journals has been significantly lower than in the West. CONCLUSION:
      The major changes in the period of transition documented in the review pose new
      challenges for psychiatry.

PMID- 16968360
TI  - Outcomes of involuntary hospital admission--a review.
AB  - INTRODUCTION: This paper reviews studies on outcomes of involuntary hospital
      admissions in general adult psychiatry, and predictors of outcomes. METHOD:
      Studies assessing observer-rated clinical change and self-rated outcomes were
      identified. Relevant databases were searched and authors were contacted. Studies
      were classified according to quality criteria. RESULTS: Eighteen studies
      fulfilled the inclusion criteria. Most involuntarily admitted patients show
      substantial clinical improvement over time. Retrospectively, between 33% and 81%
      of patients regard the admission as justified and/or the treatment as beneficial.
      Data on predictors of outcomes is limited and inconsistent. Patients with more
      marked clinical improvement tend to have more positive retrospective judgements.
      CONCLUSION: A substantial number of involuntary patients do retrospectively not
      feel that their admission was justified and beneficial. At least for this group,
      new approaches might have to be considered. Larger studies are required to
      identify predictors on which patients are likely to fall into this group.

PMID- 16968361
TI  - Health behavior in psychiatric in-patients compared with a German general
      population sample.
AB  - OBJECTIVE: To compare the health relevant behavior of psychiatric patients and
      the general population. METHOD: Health behavior of 363 psychiatric in-patients
      with ICD-10 diagnoses of schizophrenia, bipolar disorders, major depressive
      disorders and neurotic, and somatoform disorders was compared with health
      behavior of a representative sample of 7200 persons from German general
      population. RESULTS: Increased prevalence rates for smoking and illicit drug use
      were found for all diagnostic groups. Risk alcohol consumption was increased in
      patients with schizophrenia and depression. Smokers with schizophrenia had an
      excess cigarette consumption compared with general population. The number of
      unhealthy food habits was increased in all diagnostic groups, and the body mass
      index was found to be increased for patients with schizophrenia. Patients with
      depression were more physically active than general population. CONCLUSION: Poor
      health behavior is widespread in patients with all major psychiatric diagnoses.
      Interventions to reduce risk behavior and strengthen health preventive lifestyles
      are necessary.

PMID- 16968362
TI  - Pretreatment social functioning predicts 1-year outcome in early onset psychosis.
AB  - OBJECTIVE: The aim was to investigate the association of pretreatment social
      functioning (12 months before initial presentation) with symptom dimensions and
      social functioning at 1-year follow-up. METHOD: Fifty-six adolescents, age 14-18,
      first admitted for early onset psychosis, were evaluated at baseline and 1-year
      follow-up assessing psychopathology (PANSS), social functioning (Strauss and
      Carpenter Prognostic Scale), and duration of untreated psychosis (DUP). RESULTS:
      Adolescents with low pretreatment social functioning were at risk of more severe
      negative symptoms and lower social functioning at follow-up. Negative symptoms at
      baseline were less predictive and DUP was not predictive in this sample.
      CONCLUSION: Results of this study suggest a strong longitudinal inter-relatedness
      between social functioning and negative symptoms in this age group. An
      integrative treatment approach including family interventions, social skills
      training, long-term specialized work/school rehabilitation, and adequate
      antipsychotic treatment is warranted to improve both, social functioning and
      negative symptoms.

PMID- 16968363
TI  - Perinatal risk factors and infantile autism.
AB  - OBJECTIVE: Suboptimal conditions during pregnancy and birth have been suggested
      as a cause of infantile autism. We have studied the association between obstetric
      factors and infantile autism. METHOD: A population-based, matched case-control
      study of infantile autism. Conditional logistic regression was used to calculate
      odds ratios (OR) and 95% confidence intervals (CI). RESULTS: The risk of
      infantile autism was increased for mothers aged >35 years, with foreign
      citizenship, and mothers who used medicine during pregnancy. A higher risk of
      infantile autism was seen among children with low birth weight and with
      congenital malformations. Birth interventions, pathological cardiotocography,
      green amnion fluid and acidosis during delivery were not associated with
      increased risk for infantile autism. CONCLUSION: Our findings suggest that
      suboptimal birth conditions are not an independent risk factor for infantile
      autism. A high prevalence of low birth weight and birth defects among autism
      cases seems to explain the suboptimal birth outcome.

PMID- 16968364
TI  - Shared decision making for in-patients with schizophrenia.
AB  - OBJECTIVE: Patients' participation in treatment planning is being increasingly
      advocated in mental health. The model of "Shared Decision Making" (SDM) is
      proposed as a promising method of engaging patients in medical decisions and
      improving health-related outcomes. In the present study, the feasibility and
      effects of SDM for in-patients with schizophrenia should be evaluated. METHOD:
      Randomized controlled trial comparing a SDM program with routine care (n = 107).
      RESULTS: The intervention studied was feasible for most of the patients and did
      not take up more of the doctors' time. Patients in the intervention group had a
      better knowledge about their disease (P = 0.01) and a higher perceived
      involvement in medical decisions (P = 0.03). The intervention increased the
      uptake of psychoeducation (P = 0.003). CONCLUSION: Sharing medical decisions with
      acutely ill in-patients with schizophrenia is in many cases possible and improves
      important treatment patterns. This might help in destigmatizing this group of
      patients and improving schizophrenia-related health outcomes.

PMID- 16968365
TI  - Treatment costs and clinical outcome for first episode schizophrenia patients: a
      3-year follow-up of the Swedish "Parachute Project" and two comparison groups.
AB  - OBJECTIVE: To evaluate "need-specific treatment" of first episode schizophrenia
      syndrome patients. METHOD: Sixty-one consecutive first episode schizophrenia
      syndrome patients were followed over 3 years. They were compared with a
      Historical "treatment as usual" group (n = 41) and a Prospective group from a
      high quality social and biological psychiatry centre (n = 25). RESULTS:
      Symptomatic and functional outcome was significantly better compared with the
      Historical group and equal with the Prospective group. During the first year, the
      direct costs for in- and out-patient care per patient in the Parachute project
      were less than half of those in the Prospective group. CONCLUSION: The study
      confirms the feasibility, clinically and economically, with a large scale
      application of "need-specific treatments" for first episode psychotic patients.

PMID- 16968366
TI  - Forensic psychiatric assessment in European Union member states.
AB  - OBJECTIVE: To provide a structured description and cross-boundary comparison of
      legal frameworks and training standards relevant for forensic psychiatric
      assessment in European Union member states before the extension in May 2004.
      METHOD: Information on legislation and practice concerning the assessment of
      mentally disordered offenders was gathered by means of a detailed, structured
      questionnaire which was filled in by national experts. RESULTS: Legal frameworks
      for the assessment and reassessment of mentally disordered offenders and
      professional training standards in forensic psychiatry vary markedly across EU
      member states. CONCLUSION: Currently a cross-boundary harmonization of legal
      concepts appears hard to achieve. At least a formal construction and
      implementation of specialist training standards in forensic psychiatry would
      appear desirable.

PMID- 16968367
TI  - "Seeing voices": fused visual/auditory verbal hallucinations reported by three
      persons with schizophrenia-spectrum disorder.
AB  - OBJECTIVE: The neurocognitive basis of verbal/auditory hallucinations remains
      uncertain. A leading hypothesis is that these hallucinations correspond to
      ordinary inner speech mislabeled as non-self. However, some studies suggest
      pathogenic activation of receptive language neurocircuitry as the cause. A form
      of visualized verbal hallucinations not previously reported in the literature is
      described that may shed light on this controversy. METHOD: Review of three cases.
      RESULTS: Two patients described visual hallucinations of speech-like lip and
      mouth movements fused with simultaneous auditory verbal hallucinations
      superimposed on perceptions of faces of actual persons in their immediate
      environment. A third patient described similar experiences incorporated into
      visual hallucinations of human figures who also exhibited finger and hand
      movements corresponding to American Sign Language. CONCLUSION: These fused,
      multimodal verbal hallucinations seem unlikely to be due to inner speech
      mislabeled as non-self, and instead suggest top-down re-shaping of activation in
      visual processing brain centers by pathogenically active receptive language
      neurocircuitry.

PMID- 16968370
TI  - Aripiprazole in chronic schizophrenia: experiences in daily practice.

PMID- 16968372
TI  - Obsessive-compulsive disorder and acute traumatic brain injury.

PMID- 16968373
TI  - Attitude towards antipsychotics among outpatients with schizophrenia.

PMID- 16968376
TI  - The first EAO Consensus Conference 16-19 February 2006, Pfaffikon, Switzerland.

PMID- 16968377
TI  - Validity and clinical significance of biomechanical testing of implant/bone
      interface.
AB  - PURPOSE: The aim of this paper was to review the clinical literature on the
      Resonance frequency analysis (RFA) and Periotest techniques in order to assess
      the validity and prognostic value of each technique to detect implants at risk
      for failure. MATERIAL AND METHODS: A search was made using the PubMed database to
      find clinical studies using the RFA and/or Periotest techniques. RESULTS: A
      limited number of clinical reports were found. No randomized-controlled clinical
      trials or prospective cohort studies could be found for validity testing of the
      techniques. Consequently, only a narrative review was prepared to cover general
      aspects of the techniques, factors influencing measurements and the clinical
      relevance of the techniques. CONCLUSIONS: Factors such as bone density, upper or
      lower jaw, abutment length and supracrestal implant length seem to influence both
      RFA and Periotest measurements. Data suggest that high RFA and low Periotest
      values indicate successfully integrated implants and that low/decreasing RFA and
      high/increasing Periotest values may be signs of ongoing disintegration and/or
      marginal bone loss. However, single readings using any of the techniques are of
      limited clinical value. The prognostic value of the RFA and Periotest techniques
      in predicting loss of implant stability has yet to be established in prospective
      clinical studies.

PMID- 16968378
TI  - Influence of forces on peri-implant bone.
AB  - Occlusal forces affect an oral implant and the surrounding bone. According to
      bone physiology theories, bones carrying mechanical loads adapt their strength to
      the load applied on it by bone modeling/remodeling. This also applies to bone
      surrounding an oral implant. The response to an increased mechanical stress below
      a certain threshold will be a strengthening of the bone by increasing the bone
      density or apposition of bone. On the other hand, fatigue micro-damage resulting
      in bone resorption may be the result of mechanical stress beyond this threshold.
      In the present paper literature dealing with the relationship between forces on
      oral implants and the surrounding bone is reviewed. Randomized controlled as well
      as prospective cohorts studies were not found. Although the results are
      conflicting, animal experimental studies have shown that occlusal load might
      result in marginal bone loss around oral implants or complete loss of
      osseointegration. In clinical studies an association between the loading
      conditions and marginal bone loss around oral implants or complete loss of
      osseointegration has been stated, but a causative relationship has not been
      shown.

PMID- 16968379
TI  - Indications for immediate loading of implants and implant success.
AB  - It was the aim of this review to compare the survival and success rates of
      immediately loaded dental implants with those of conventionally loaded dental
      implants, based on prospective controlled studies and prospective studies without
      controls. Studies on immediate loading were identified in the current literature
      by electronic and hand searches. Only clinical data on root-form or cylindrical
      threaded oral implants were included. For immediate loading of oral implants in
      the edentulous and partially dentate, mandible and maxilla controlled studies
      could be found. All of these studies were based on limited patient numbers.
      Therefore, definitive conclusions could not be drawn concerning survival and
      success rates of immediately loaded implants compared with conventionally loaded
      implants. The compilation of the current literature shows that prospective
      controlled studies as well as prospective studies without controls using several
      different approaches to immediate loading have demonstrated high implant survival
      and success rates. However, more high-level evidence-based studies are needed to
      demonstrate the relative merits of immediate loading compared with conventional
      loading in all potential applications.

PMID- 16968380
TI  - Impact of implant length and diameter on survival rates.
AB  - INTRODUCTION: Despite the high success rates of endosseous oral implants,
      restrictions have been advocated to their placement with regard to the bone
      available in height and volume. The use of short or nonstandard-diameter implants
      could be one way to overcome this limitation. MATERIAL AND METHODS: In order to
      explore the relationship between implant survival rates and their length and
      diameter, a Medline and a hand search was conducted covering the period 1990
      2005. Papers were included which reported: (1) relevant data on implant length
      and diameter, (2) implant survival rates; either clearly indicated or calculable
      from data in the paper, (3) clearly defined criteria for implant failure, and in
      which (4) implants were placed in healed sites and (5) studies were in human
      subjects. RESULTS: A total of 53 human studies fulfilled the inclusion criteria.
      Concerning implant length, a relatively high number of published studies (12)
      indicated an increased failure rate with short implants which was associated with
      operators' learning curves, a routine surgical preparation (independent of the
      bone density), the use of machined-surfaced implants, and the placement in sites
      with poor bone density. Recent publications (22) reporting an adapted surgical
      preparation and the use of textured-surfaced implants have indicated survival
      rates of short implants comparable with those obtained with longer ones.
      Considering implant diameter, a few publications on wide-diameter implants have
      reported an increased failure rate, which was mainly associated with the
      operators' learning curves, poor bone density, implant design and site
      preparation, and the use of a wide implant when primary stability had not been
      achieved with a standard-diameter implant. More recent publications with an
      adapted surgical preparation, new implant designs and adequate indications have
      demonstrated that implant survival rate and diameter have no relationship.
      DISCUSSION: When surgical preparation is related to bone density, textured
      surfaced implants are employed, operators' surgical skills are developed, and
      indications for implant treatment duly considered, the survival rates for short
      and for wide-diameter implants has been found to be comparable with those
      obtained with longer implants and those of a standard diameter. The use of a
      short or wide implant may be considered in sites thought unfavourable for implant
      success, such as those associated with bone resorption or previous injury and
      trauma. While in these situations implant failure rates may be increased,
      outcomes should be compared with those associated with advanced surgical
      procedure such as bone grafting, sinus lifting, and the transposition of the
      alveolar nerve.

PMID- 16968381
TI  - Biomechanical aspects of oral implants. Consensus report of Working Group 1.
AB  - The method used by the working group was an iterative process based upon a
      structured review of the relevant literature by a group of reporters. The review
      papers were circulated to the members of the group before the conference and
      formed the basis for subsequent discussions. Each paper was subject to detailed
      collective analysis and subsequently modified on the basis of the panel's
      discussions and referenced to additional relevant literature where appropriate.
      The group assessed the levels of evidence for the statements made in the
      supporting documentation and recognized that it was necessary to adopt a
      compromise between acceptance of the lowest level, resulting in the largest body
      of material, and the highest level, which, in some cases, produced little
      evidence. While this approach does not represent endorsement of lower evidence
      levels per se, it was designed to provide conclusions of clinical utility within
      the existing knowledge base. The consensus statements were prepared after a
      detailed consideration of the papers submitted to the workshop by the working
      group. The papers were scrutinized, amended and approved by the group. The basis
      of each paper is described in the section on 'search strategy' and defines the
      parameters within which the consensus statements were prepared.

PMID- 16968382
TI  - The effect of material characteristics, of surface topography and of implant
      components and connections on soft tissue integration: a literature review.

PMID- 16968383
TI  - Effect of material characteristics and/or surface topography on biofilm
      development.
AB  - BACKGROUND: From an ecological viewpoint, the oral cavity, in fact the oro
      pharynx, is an 'open growth system'. It undergoes an uninterrupted introduction
      and removal of both microorganisms and nutrients. In order to survive within the
      oro-pharyngeal area, bacteria need to adhere either to the soft or hard tissues
      in order to resist shear forces. The fast turn-over of the oral lining epithelia
      (shedding 3 x/day) is an efficient defence mechanism as it prevents the
      accumulation of large masses of microorganisms. Teeth, dentures, or endosseous
      implants, however, providing non-shedding surfaces, allow the formation of thick
      biofilms. In general, the established biofilm maintains an equilibrium with the
      host. An uncontrolled accumulation and/or metabolism of bacteria on the hard
      surfaces forms, however, the primary cause of dental caries, gingivitis,
      periodontitis, peri-implantitis, and stomatitis. OBJECTIVES: This systematic
      review aimed to evaluate critically the impact of surface characteristics (free
      energy, roughness, chemistry) on the de novo biofilm formation, especially in the
      supragingival and to a lesser extent in the subgingival areas. METHODS: An
      electronic Medline search (from 1966 until July 2005) was conducted applying the
      following search items: 'biofilm formation and dental/oral implants/surface
      characteristics', 'surface characteristics and implants', 'biofilm formation and
      oral', 'plaque/biofilm and roughness', 'plaque/biofilm and surface free energy',
      and 'plaque formation and implants'. Only clinical studies within the oro
      pharyngeal area were included. RESULTS: From a series of split-mouth studies, it
      could be concluded that both an increase in surface roughness above the R(a)
      threshold of 0.2 microm and/or of the surface-free energy facilitates biofilm
      formation on restorative materials. When both surface characteristics interact
      with each other, surface roughness was found to be predominant. The biofilm
      formation is also influenced by the type (chemical composition) of biomaterial or
      the type of coating. Direct comparisons in biofilm formation on different
      transmucosal implant surfaces are scars. CONCLUSIONS: Extrapolation of data from
      studies on different restorative materials seems to indicate that transmucosal
      implant surfaces with a higher surface roughness/surface free energy facilitate
      biofilm formation.

PMID- 16968384
TI  - A systematic review of marginal soft tissue at implants subjected to immediate
      loading or immediate restoration.
AB  - OBJECTIVES: The objective of this systematic review was to critically evaluate
      marginal soft-tissue aspects at implants subjected to immediate loading or
      immediate restoration. METHODS: An electronic Medline search from 1966 up to
      August 2005 was conducted to identify prospective and retrospective studies on
      immediate implant loading. The search strategy was complemented by hand searching
      in peer-reviewed journals. Studies reporting on soft-tissue aspects at implants
      subjected to immediate loading or immediate restoration and with a follow-up time
      of at least 1 year were included. Assessment of identified studies and data
      extraction was performed independently by two reviewers. An attempt was made to
      isolate and categorize studies with similar protocols in order to identify trends
      and relevant factors. Variables that were considered included marginal and
      interproximal soft-tissue stability, marginal plaque accumulation, probing depth,
      bleeding on probing, peri-implant mucositis and peri-implantitis. RESULTS: From
      an initial yield of 581 titles, 240 articles were selected for text analysis,
      finally resulting in 17 studies that met the inclusion criteria. Six studies on
      immediate implant loading or restoration were controlled studies, whereas the
      remainder was prospective case series. Seven studies reported on a 1-year data,
      and the longest follow-up within the included studies was 4 years. The total
      number of patients treated within the 17 studies was 432 including a total 706
      implants studied. Overall, the articles reported on many different procedures and
      follow-up times, time points and evaluated soft-tissue parameters varied
      considerably between the different articles. CONCLUSION: Within the limits of the
      evaluated data it can be cautiously concluded that once immediately loaded or
      restored implants integrate successfully, they appear to show a soft-tissue
      reaction with regard to periodontal as well as morphologic aspects comparable
      with those of conventionally loaded implants. However, follow-up periods are
      generally short, number of patients and/or implants per study are few, and most
      studies present only limited data on peri-implant soft-tissue evaluation. More
      accurate long-term studies with a stronger study design (i.e., RCT) reporting
      more detailed on treatment and follow-up protocols are required to allow for
      proper comparisons and conclusions.

PMID- 16968385
TI  - Soft-tissue integration of implants. Consensus report of Working Group 2.

PMID- 16968386
TI  - Systemic diseases affecting osseointegration therapy.
AB  - OBJECTIVES: To evaluate the impact of systemic diseases and their treatment on
      the success of osseointegration therapy. MATERIAL AND METHODS: A search was made
      to find human studies including subjects treated with osseointegrated oral
      implants, with a diagnosis of 11 systemic diseases, and reporting at least
      implant survival. RESULTS: For most conditions, no studies comparing patients
      with and without the condition in a controlled setting were found. The evidence
      to recommend implant therapy was low and consisted in presentations of some
      successfully treated cases. With regard to diabetes, three types of reports were
      found: eight case series of diabetic patients treated with implants, six cross
      sectional, longitudinal or retrospective evaluations of groups of subjects
      treated with implants, including some diabetic patients, and one matched control
      retrospective chart survey. The heterogeneity of the material and the method of
      data reporting precluded a formal meta-analysis. No unequivocal tendency for
      subjects with diabetes to have higher failure rates emerged, but the largest of
      these studies indicated a significant increase in the relative risk of implant
      failure with diabetes. The data obtained from 17 papers reporting data from
      osteoporotic patients were also heterogeneous. The evidence for an association of
      osteoporosis and implant failure was low. CONCLUSIONS: The level of evidence
      indicative of absolute and relative contraindications for implant therapy due to
      systemic diseases is low. Many conditions have been listed as potentially
      critical, but studies comparing patients with and without the condition in a
      controlled setting are sparse.

PMID- 16968387
TI  - Outcome of implant therapy in patients with previous tooth loss due to
      periodontitis.
AB  - BACKGROUND: It is frequently debated whether implant treatment in individuals
      with previous tooth loss due to periodontitis is characterized by an increased
      incidence of implant loss and peri-implantitis. OBJECTIVE: The objective of the
      present systematic review was to assess whether individuals with previous tooth
      loss due to periodontitis have an increased risk of loss of suprastructures, loss
      of implants, peri-implantitis, and peri-implant marginal bone loss as compared
      with individuals with previous tooth loss due to reasons other than
      periodontitis. SEARCH STRATEGY: Studies considered for inclusion were searched in
      MEDLINE (PubMed) and relevant journals were hand searched. Moreover, reference
      lists of articles selected for full-text screening as well as previously
      published reviews relevant for the present systematic review were searched. The
      search was performed by one reviewer and was restricted to human studies
      published from January 1, 1980 to January 1, 2006. No language restrictions were
      applied. SELECTION CRITERIA: Prospective and retrospective cohort studies with at
      least a 5-year follow-up comparing the outcome of implant treatment in
      individuals with periodontitis-associated and non-periodontitis-associated tooth
      loss, respectively, were included. The outcome measures were survival of
      suprastructures, survival of implants, occurrence of peri-implantitis, and peri
      implant marginal bone loss. The 5- and 10-year time points were evaluated. DATA
      COLLECTION AND ANALYSIS: Screening of eligible studies, methodological quality
      assessment, and data extraction were conducted in duplicate and independently by
      two of the authors. The authors were contacted for missing information. Results
      were expressed as random effect models using weighted mean differences for
      continuous outcomes and relative risk for dichotomous outcomes with 95%
      confidence intervals (CIs). MAIN RESULTS: Two studies with a 5- and 10-year
      follow-up, respectively, were identified including a total of 33 patients with
      tooth loss due to periodontitis and 70 patients with non-periodontitis-associated
      tooth loss. There was no significant difference in the survival of the
      suprastructures after 5 years. Furthermore, there were no significant differences
      in the survival of the implants after 5 and 10 years. However, there were
      significantly more patients affected by peri-implantitis in the group with
      periodontitis-associated tooth loss during the 10-year follow-up period, risk
      ratio (RR) 9 (95% CI 3.94-20.57). Moreover, significantly increased peri-implant
      marginal bone loss was observed in patients with periodontitis-associated tooth
      loss after 5 years, mean difference 0.5 mm (95% CI 0.06-0.94). CONCLUSIONS: The
      survival of the suprastructures and the implants was not significantly different
      in individuals with periodontitis-associated and non-periodontitis-associated
      tooth loss. However, significantly increased incidence of peri-implantitis and
      significantly increased peri-implant marginal bone loss were revealed in
      individuals with periodontitis-associated tooth loss. The small sample size and
      the methodological quality assessment of the two studies suggest that the results
      should be interpreted with caution. Consequently, further long-term studies
      focusing particularly on the outcome of implant treatment in young adults with
      aggressive periodontitis are needed before final conclusions can be drawn about
      the outcome of implant treatment in patients with a history of periodontitis.

PMID- 16968388
TI  - Bone density and primary stability in implant therapy.
AB  - INTRODUCTION: To improve patient comfort, deviations from the very successful
      standard osseointegration protocol are being developed. To keep implant failure
      rates as low as possible, the most perfect treatment planning and a good patient
      selection are extremely important. Because bone density plays an important role
      in implant outcome, known relations of bone density could improve treatment
      planning. MATERIAL AND METHODS: A Pubmed search revealed 66 manuscripts
      investigating and discussing bone density of human jawbone whether or not related
      to implant stability or outcome. Forty-five of these will be discussed in this
      review. RESULTS AND DISCUSSION: Many pre-operative methods of jawbone density
      assessment are available. Most of those techniques correlate well with one
      another. Some are more elaborate to use in clinical practice. Primary stability
      measurements show significant correlations with different bone densities and also
      with implant outcome; however, not many studies investigate both at the same
      time. CONCLUSION: To investigate the outcome of adaptation methods of the
      surgical protocol with regard to the jawbone density, an objective pre-surgical
      determination of bone density is necessary.

PMID- 16968389
TI  - Augmentation procedures for the rehabilitation of deficient edentulous ridges
      with oral implants.
AB  - OBJECTIVES: To analyze publications related to augmentation procedures and to
      evaluate the success of different surgical techniques for ridge reconstruction
      and the survival/success rates of implants placed in the augmented areas.
      MATERIAL AND METHODS: Clinical investigations published in English involving at
      least 5 patients and with a minimum follow-up of 6 months were included. The
      following procedures were considered: a) Guided bone regeneration (GBR); 2) Onlay
      bone grafts; 3) Inlay grafts; 4) Bone splitting for ridge expansion (RE); 5)
      Distraction osteogenesis (DO); and 6) Revascularized flaps. Success rates of
      augmentation procedures and related morbidity, as well as survival and success
      rates of implants placed in the augmented sites were analyzed. RESULTS: Success
      rates of surgical procedures ranged from 60% to 100% for GBR, from 92% to 100%
      for onlay bone grafts, from 98% to 100% for ridge expansion techniques, from
      96,7% to 100% for DO, and was 87.5% for revascularized flaps, whereas survival
      rates of implants ranged from 92% to 100% for GBR, from 60% to 100% for onlay
      bone grafts, from 91% to 97.3% for RE, from 90.4% to 100% for DO, and, finally,
      was 88.2% for revascularized flaps. CONCLUSION: On the basis of available data it
      was shown that it was difficult to demonstrate that a particular surgical
      procedure offered better outcome as compared to another. The main limit
      encountered in this review has been the overall poor methodological quality of
      the published articles. Therefore larger well-designed long term trials are
      needed.

PMID- 16968390
TI  - Local and systemic conditions potentially compromising osseointegration.
      Consensus report of Working Group 3.

PMID- 16968391
TI  - The role of the cellular prion protein in the immune system.
AB  - Prion protein (PrP) plays a key role in the pathogenesis of prion diseases.
      However, the normal function of the protein remains unclear. The cellular isoform
      (PrP(C)) is expressed widely in the immune system, in haematopoietic stem cells
      and mature lymphoid and myeloid compartments in addition to cells of the central
      nervous system. It is up-regulated in T cell activation and may be expressed at
      higher levels by specialized classes of lymphocyte. Furthermore, antibody cross
      linking of surface PrP modulates T cell activation and leads to rearrangements of
      lipid raft constituents and increased phosphorylation of signalling proteins.
      These findings appear to indicate an important but, as yet, ill-defined role in T
      cell function. Although PrP(-/-) mice have been reported to have only minor
      alterations in immune function, recent work has suggested that PrP is required
      for self-renewal of haematopoietic stem cells. Here, we consider the evidence for
      a distinctive role for PrP(C) in the immune system and what the effects of anti
      prion therapeutics may be on immune function.

PMID- 16968392
TI  - Longitudinal epitope analysis of insulin-binding antibodies in type 1 diabetes.
AB  - Autoantibodies to insulin (IAA) are one of the first markers of the autoimmune
      process leading to type 1 diabetes (T1D). While other autoantibodies in T1D have
      been studied extensively, relatively little is known about IAA and their binding
      specificities, especially after insulin treatment is initiated. We hypothesize
      that insulin antibodies (IA) that develop upon initiation of insulin treatment
      differ in their epitope specificities from IAA. We analysed insulin antibody
      binding specificities in longitudinal samples of T1D patients (n = 49). Samples
      were taken at clinical diagnosis of disease and after insulin treatment was
      initiated. The epitope specificities were analysed using recombinant Fab (rFab)
      derived from insulin-specific monoclonal antibodies AE9D6 and CG7C7. Binding of
      radiolabelled insulin by samples taken at onset of the disease was significantly
      reduced in the presence of rFab CG7C7 and AE9D6. rFab AE9D6 competed sera binding
      to insulin significantly better than rFab CG7C7 (P = 0.02). Binding to the AE9D6
      defined epitope in the initial sample was correlated inversely with age at onset
      (P = 0.005). The binding to the AE9D6-defined epitope increased significantly (P
      < 0.0001) after 3 months of insulin treatment. Binding to the CG7C7-defined
      epitope did not change during the analysed period of 12 months. We conclude that
      epitopes recognized by insulin binding antibodies can be identified using
      monoclonal insulin-specific rFab as competitors. Using this approach we observed
      that insulin treatment is accompanied by a change in epitope specificities in the
      emerging IA.

PMID- 16968393
TI  - Agreement of anti-neutrophil cytoplasmic antibody measurements obtained from
      serum and plasma.
AB  - Serum and plasma are used interchangeably to measure anti-neutrophil cytoplasmic
      antibodies (ANCA), even though the release of ANCA target antigens during the
      preparation of serum could affect ANCA assays and cause discrepancies between the
      results obtained from serum and plasma. To what extent ANCA test results obtained
      from serum agree and correlate with results from plasma remains unknown.
      Therefore, a comprehensive comparison was performed using serum and plasma
      samples which were collected in 175 patients with active Wegener's granulomatosis
      at enrollment of a recent randomized trial. These paired serum and plasma samples
      were subjected to parallel ANCA testing by standard indirect immunofluorescence
      on ethanol-fixed neutrophils, a direct enzyme-linked immunoassay (ELISA) for
      proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA, and two different capture
      ELISAs for PR3-ANCA. The concordance of categorical serum and plasma ANCA results
      was assessed using kappa-coefficients. These were > 0.8 for all assays,
      indicating a very good concordance between positive and negative serum and plasma
      results. Spearman's correlation coefficients for serum and plasma PR3-ANCA values
      obtained by direct ELISA and both capture ELISAs were > or = 0.95 (P < 0.0001).
      Our study shows that serum and plasma samples can be used interchangeably for
      measuring ANCA.

PMID- 16968394
TI  - Interleukin-18 overexpression as a hallmark of the activity of autoimmune
      inflammatory myopathies.
AB  - The objective of this study was to explore the role of interleukin (IL)-18 in
      patients with inflammatory myopathies (IM) such as dermatomyositis (DM) and
      polymyositis (PM) in relation to the possible predominance of a Th1 immune
      response in their pathogenesis. Serum concentrations of IL-18, interferon (IFN)
      gamma, IL-4 and IL-6 were measured in six patients by enzyme-linked immunosorbent
      assay (ELISA). IL-18 expression was evaluated by in situ hybridization (ISH),
      whereas CD68, CD8 and CD83 were investigated by immunohistochemistry (IHC) to
      define the main producers of IL-18. Lastly, the expression of both IL-18 receptor
      (IL-18R) and monocyte chemoattractant protein (MCP)-1 was also explored by IHC.
      High serum levels of IL-18 and IFN-gamma, and conversely low titres of IL-4 and
      IL-6, were demonstrated in both diseases. In addition, IL-18 was overexpressed in
      muscle biopsy specimens from patients with IM. Both macrophages and dendritic
      cells (DC) surrounding either perivascular and perimysium areas in DM or
      endomysium in PM were the main producers of IL-18. Endothelial cells (EC), smooth
      muscle cells (SMC) and CD8(+) T cells expressed a high content of IL-18R. Vessel
      cells overexpressed MCP-1 in parallel with IL-18R. High concentrations of serum
      IL-18 as well as muscular up-regulation of IL-18 and IL-18R suggest that
      deregulation of the IL-18/IL-18R pathway is a pathogenetic mechanism in IM.
      Measurement of IL-18 may thus predict the severity of both DM and PM.

PMID- 16968395
TI  - Yersinia enterocolitica infection does not confer an increased risk of thyroid
      antibodies: evidence from a Danish twin study.
AB  - Understanding of the aetiological basis of thyroid autoimmunity may be gained by
      studying the early stages of the disease process. We aimed to (1) investigate the
      relationship between thyroid antibody status and Yersinia enterocolitica (YE)
      infection in euthyroid subjects and (2) explore the relative importance of
      genetic and environmental risk factors in the acquisition of YE infection. The
      association between thyroid antibody status and YE infection was explored using a
      case-control design. Furthermore, thyroid antibody-positive twins were compared
      with their thyroid antibody-negative co-twin. In 468 twins, IgA and IgG
      antibodies to virulence-associated outer-membrane proteins (YOPs) of YE were
      measured. Of these, 147 were thyroid antibody-positive (cases). A total of 147
      age- and gender-matched twins were chosen as controls. The prevalence of YOP
      antibodies was lower among thyroid antibody-positive individuals than among
      controls. Yersinia infection was not associated with a positive thyroid antibody
      status: the odds ratio (with 95% CI) for YOP IgA-ab was 0.66 (0.42-1.05), P =
      0.078 and for YOP IgG-ab it was 0.95 (0.60-1.50), P = 0.816. Within discordant
      twin pairs, the thyroid antibody-positive twin did not have an increased risk of
      Yersinia infection compared to the thyroid antibody-negative co-twin [odds ratio:
      YOP IgA-Ab: 0.94 (0.49-1.83), P = 0.866, and YOP IgG-Ab: 1.35 (0.72-2.53), P =
      0.345]; 41% (95% CI 10-67% of the liability of being YOP antibody-positive was
      due to genetic effects. In conclusion, Yersinia infection does not confer an
      increased risk of thyroid antibodies. The genetic contribution in the acquisition
      of Yersinia infection is modest.

PMID- 16968396
TI  - Alterations in peripheral blood lymphocyte cytokine expression in obesity.
AB  - Obesity is characterized by alterations in immune and inflammatory function. In
      order to evaluate the potential role of cytokine expression by peripheral blood
      mononuclear cells (PBMC) in obesity-associated inflammation, we studied serum
      protein levels and mRNA levels in PBMC of interleukin (IL)-6, IL-1beta, tumour
      necrosis factor (TNF)-alpha and IL-1Ra in nine lean and 10 obese subjects. Serum
      IL-1beta was undetectable, IL-1Ra serum levels were elevated, serum levels of TNF
      alpha were decreased and serum levels of IL-6 were similar in obese subjects
      compared to lean subjects, while transcript levels of IL-6, IL-1beta and TNF
      alpha, but not IL-1Ra, were decreased in PBMC from obese subjects. PBMC from
      obese subjects did, however, up-regulate cytokine expression in response to
      leptin. Thus, obesity-associated changes in IL-1Ra serum levels and IL-6 mRNA
      levels were not correlated with changes in cognate mRNA and serum levels,
      respectively, while TNF-alpha serum levels and PBMC mRNA levels were both
      decreased in obese patients. While immune alterations in obesity are manifest in
      peripheral blood lymphocytes, the general lack of correlation between altered
      serum levels and altered PBMC gene expression suggests that PBMC may not be the
      source of aberrant serum cytokine levels in obesity.

PMID- 16968397
TI  - High-dose intravenous immunoglobulin pulse therapy in patients with progressive
      immunoglobulin A nephropathy: a long-term follow-up.
AB  - In progressive immunoglobulin A nephropathy (IgAN), intravenous immunoglobulin
      (IVIg) treatment has been used to delay disease progression, but the long-term
      efficacy is largely unknown. We report the clinical outcomes after IVIg therapy
      in six male patients with progressive IgAN [median glomerular filtration rate
      (GFR) 31 ml/min per 1.73 m(2)] followed for a median observation period of 8
      years. In this single-arm, non-randomized study, IVIg was given monthly at a dose
      of 2 g/kg body weight for 6 months. The course of renal function was assessed by
      linear regression analysis of GFR and proteinuria, and was compared to eight
      patients with IgAN (median GFR 29 ml/min per 1.73 m(2)) without IVIg as a
      contemporaneous control group. IgAN disease progression was delayed after IVIg
      therapy on average for 3 years. The mean loss of renal function decreased from 
      1.05 ml/min per month to -0.15 ml/min per month (P = 0.024) and proteinuria
      decreased from 2.4 g/l to 1.0 g/l (P = 0.015). The primary end-point (GFR < 10
      ml/min or relapse) occurred 5.2 years (median; range 0.4-8.8) after the first
      IVIg pulse, and after 1.3 years (median; range 0.8-2.4) in the control group (P =
      0.043). In Kaplan-Meier analysis, the median renal survival time with IVIg was
      prolonged by 3.5 years (IVIg 4.7 years versus control 1.2 years; P = 0.006). IVIg
      pulse therapy may be considered as a treatment option to reduce the loss of renal
      function and improve proteinuria in patients with progressive IgAN.

PMID- 16968398
TI  - Coincidence of different structures of mucosa-associated lymphoid tissue (MALT)
      in the respiratory tract of children: no indications for enhanced mucosal
      immunostimulation in sudden infant death syndrome (SIDS).
AB  - Mucosa-associated lymphoid tissue (MALT) is the principal inductive site for
      mucosal immune responses that are capable of T and B cell responses and antigen
      specific responses. In previous independent studies different structures of MALT,
      e.g. bronchus-, larynx- and nose-associated lymphoid tissue (BALT, LALT, NALT)
      have been described separately in various frequencies in the human respiratory
      tract over life spans. Because upper respiratory tract infections are common in
      infants, dysregulations of mucosal immune responses might be seriously involved
      in the aetiology of sudden infant death syndrome (SIDS). In the present study the
      coincidental occurrence of the three different MALT structures in the respiratory
      tract within the same patients were studied, and cases of SIDS and children who
      had died from different traumatic and natural causes of death (non-SIDS) were
      compared. First, the frequency of BALT and LALT in 46 children (35 SIDS, 11 non
      SIDS) with or without NALT were examined. A tendency was found of a coincidence
      of respiratory MALT structures. In 50 additional cases of infant death (30 SIDS,
      20 non-SIDS) from the multi-centric German Study on Sudden Infant Death Syndrome
      (GeSID) where death had occurred in the first year of life, the coincidence was
      evaluated. A coincidental occurrence of BALT, LALT and NALT or BALT and LALT
      (each about 30%) was found in both groups, whereby the coincidence in SIDS and
      the control patients did not differ. Interestingly, the children with
      coincidental MALT were strikingly older, supporting the hypothesis of respiratory
      MALT formation via environmental stimulation over time.

PMID- 16968399
TI  - Post-translational modifications of the major linear epitope 169-190aa of Ro60
      kDa autoantigen alter the autoantibody binding.
AB  - Ro60 kDa is a member of the Ro/LaRNP ribonucleoprotein complex and its major
      linear B cell epitope, corresponding to the region 169-190aa, has been found to
      be the initial target of the autoimmune response in patients with systemic lupus
      erythematosus. This sequence contains one serine and two arginine amino acid
      residues, which can potentially be modified post-translationally by
      phosphorylation or citrullination, respectively. The aim of this study was to
      develop an immunoassay for anti-Ro60 kDa epitope antibody detection and to
      investigate the changes in the antigenicity of the Ro60 kDa epitope when it is
      post-translationally modified, by either citrullination or phosphorylation.
      Peptide analogues corresponding to the unmodified form of the epitope, its
      phosphorylated form, and a form with both arginine residues citrullinated were
      synthesized. The peptide coating conditions were investigated and it was found
      that the use of highly hydrophilic surfaces increase the efficiency of the
      coating, as well as the sensitivity of the method for anti-peptide antibody
      detection. All peptides were tested by the optimized enzyme-linked immunosorbent
      assay (ELISA) against 119 sera from patients with primary Sjogren's syndrome,
      systemic lupus erythematosus and rheumatoid arthritis with anti-Ro/SSA
      reactivity, 20 sera from patients with systemic diseases without anti-Ro/SSA
      immune reactivity, as well as against 65 sera from normal individuals. A large
      proportion of the tested sera reacted against all three peptide analogues,
      although with a preference for the unmodified form of the epitope. In conclusion,
      post-translational modifications of the major Ro60 kDa B cell epitope can alter
      the autoantibody binding.

PMID- 16968400
TI  - Cellular autoreactivity against heat shock protein 60 in renal transplant
      patients: peripheral and graft-infiltrating responses.
AB  - Autoreactivity to heat shock protein 60 (Hsp60) has been implicated in the
      pathogenesis and regulation of chronic inflammation, especially in autoimmune
      diseases. In transplantation, there is a lack of information regarding the
      cytokine profile and specificity of cells that recognize self-Hsp60 as well as
      the kinetics of autoreactivity following transplantation. We studied the cellular
      reactivity of peripheral and graft-infiltrating lymphocytes against Hsp60 in
      renal transplant patients. Cytokine production induced by this protein in
      peripheral blood mononuclear cells indicated a predominance of interleukin (IL)
      10 during the late post-transplantation period, mainly in response to
      intermediate and C-terminal peptides. Patients with chronic rejection presented
      reactivity to Hsp60 with a higher IL-10/interferon (IFN)-gamma ratio compared to
      long-term clinically stable patients. Graft-infiltrating T cell lines, cocultured
      with antigen-presenting cells, preferentially produced IL-10 after Hsp60
      stimulation. These results suggest that, besides its proinflammatory activity,
      autoreactivity to Hsp60 in transplantation may also have a regulatory role.

PMID- 16968401
TI  - Relevance of neutrophils in the murine model of haemolytic uraemic syndrome:
      mechanisms involved in Shiga toxin type 2-induced neutrophilia.
AB  - It has been demonstrated that infections due to Shiga toxins (Stx) producing
      Escherichia coli are the main cause of the haemolytic uraemic syndrome (HUS).
      However, the contribution of the inflammatory response in the pathogenesis of the
      disease has also been well established. Neutrophils (PMN) represent a central
      component of inflammation during infections, and patients with high peripheral
      PMN counts at presentation have a poor prognosis. The mouse model of HUS, by
      intravenous injection of pure Stx type 2 (Stx2), reproduces human neutrophilia
      and allows the study of early events in the course of Stx2-induced
      pathophysiological mechanisms. The aim of this study was to address the
      contribution of PMN on Stx2 toxicity in a murine model of HUS, by evaluating the
      survival and renal damage in mice in which the granulocytic population was
      depleted. We found that the absence of PMN reduced Stx2-induced lethal effects
      and renal damage. We also investigated the mechanisms underlying Stx2-induced
      neutrophilia, studying the influence of Stx2 on myelopoyesis, on the emergence of
      cells from the bone marrow and on the in vivo migration into tissues. Stx2
      administration led to an accelerated release of bone marrow cells, which egress
      at an earlier stage of maturation, together with an increase in the proliferation
      of myeloid progenitors. Moreover, Stx2-treated mice exhibited a lower migratory
      capacity to a local inflammatory site. In conclusion, PMN are essential in the
      pathogenesis of HUS and neutrophilia is not merely an epiphenomenon, but
      contributes to Stx2-damaging mechanism by potentiating Stx2 toxicity.

PMID- 16968403
TI  - Mycobacterium tuberculosis-susceptible I/St mice develop severe disease following
      infection with taxonomically distant bacteria, Salmonella enterica and Chlamydia
      pneumoniae.
AB  - Mice of I/St strain develop severe lung inflammation and die shortly following
      infection with virulent mycobacteria. To find out whether tuberculosis (TB)
      susceptible I/St mice are susceptible to other intracellular bacteria, we
      investigated two different taxonomically distant pathogens, Chlamydia pneumoniae
      and Salmonella enterica serovar Typhimurium. Comparison of I/St and TB-resistant
      A/Sn mice (both Nramp1(r)) demonstrated that the former are more susceptible to
      both salmonella and chlamydia, displaying a significantly shortened survival time
      following challenge. Lung pathology develops more rapidly in I/St compared to
      A/Sn mice following infection with chlamydia, despite their similar ability to
      control bacterial multiplication. Following infection with salmonella,
      substantial ( approximately 3 log) but very short (second day post-infection)
      interstrain differences in bacterial loads were observed, accompanied by higher
      levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha in the
      peritoneal cavities of I/St mice. I/St macrophages were more permissive for
      salmonella growth during the first 24 h following infection in vitro. Because the
      prominent differences in survival time did not correlate with permanent
      differences in bacterial multiplication, we suggest that both infections trigger
      fatal pathological processes whose dynamics depend strongly upon the host
      genetics.

PMID- 16968402
TI  - Inhibition of donor-derived T cells trafficking into target organs by FTY720
      during acute graft-versus-host disease in small bowel transplantation.
AB  - In small bowel transplantation (SBTx), graft-versus-host disease (GVHD) is
      mediated by donor-derived T cells recognizing host major histocompatibility
      complex (MHC) alloantigens, and represents an important immunological event
      influencing life in experimental and clinical situations. We evaluated the
      possibility that a new sphingosine 1-phosphate receptor agonist, FTY720, could
      diminish GVHD in a rat SBTx model through traffic alteration of donor-derived T
      cells in target organs. Heterotopic SBTx was performed using a parent (WF)-into
      F(1) (WF x ACI) rat combination. Recipient survival, body weight, histopathology,
      donor-derived T cell subpopulation and cytokine production were compared with
      untreated controls. FTY720 inhibited lethality and histopathological changes in
      target organs when administered at 0.5 mg/kg, possibly due to sequestration of
      donor-derived T cells in the intestinal graft. FTY720 caused a significant
      reduction in donor T cell numbers in target organs by promoting these cells to
      home into donor, but not recipient, secondary lymphoid tissues. FTY720
      significantly decreased production of interferon (IFN)-gamma in target organs.
      These findings indicate that FTY720 effectively reduced recirculation of
      activated donor-derived T cells and recruitment to target organs in GVHD, and was
      also associated with down-regulated IFN-gamma production. These properties may
      offer the potential to treat ongoing GVHD in SBTx.

PMID- 16968404
TI  - Hormonal change and cytokine mRNA expression in peripheral blood mononuclear
      cells during the development of canine autoimmune thyroiditis.
AB  - To elucidate the hormonal change and alteration in cytokine expression in
      peripheral blood mononuclear cells (PBMC) during the early stage of autoimmune
      thyroiditis, we have developed a canine model of this disease, in which normal
      dogs were immunized with bovine thyroglobulin (Tg) and/or canine thyroid extract.
      Serum samples were collected weekly, anti-canine Tg antibody was measured by
      enzyme-linked immunosorbent assay (ELISA) and thyroid stimulating hormone (TSH)
      and total T4 levels by radioimmunoassay. We also assayed T lymphocyte
      proliferation in response to Tg, as well as measuring cytokine mRNA by
      semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). All
      six dogs immunized with bovine Tg had both canine Tg autoantibody and anti-T4
      antibody. When the sample from the highest TgAA titre time-point was compared
      with baseline the expression of mRNA encoding the Th1-type cytokine such as
      interferon (IFN)-gamma, interleukin (IL)-18 and IL-15 was increased during the
      development of autoimmune thyroiditis. Expression of the Th2-type cytokine, IL-6
      showed minimal change and IL-4 expression was not detected in any of the samples.
      Expression of the T suppressive cytokine, IL-10 and transforming growth factor
      (TGF)-beta was increased in the presence of antigen stimulation. These findings
      suggest that, although autoimmune thyroiditis is an organ-specific autoimmune
      disease, systemic cytokine mRNA expression is also changed.

PMID- 16968405
TI  - Interleukin-12 is involved in the enhancement of human natural killer cell
      activity by Lactobacillus casei Shirota.
AB  - We conducted a placebo-controlled, cross-over trial to examine the effect of
      Lactobacillus casei Shirota (LcS) on natural killer (NK) cell activity in humans.
      NK cell activity exhibited a declining trend during the period of placebo
      ingestion, but NK cell activity increased after intake for 3 weeks of fermented
      milk containing 4 x 10(10) live LcS. When human peripheral blood mononuclear
      cells were cultured in the presence of heat-killed LcS, NK cell activity was
      enhanced. The ability of LcS to enhance NK cell activity and induce interleukin
      (IL)-12 production was correlated, and the addition of anti-IL-12 monoclonal
      antibody reduced the enhancement of NK cell activity triggered by LcS. In
      addition, separation of NK cells from LcS-stimulated monocytes with membrane
      filter reduced NK cell activity to the intermediate level and almost deprived
      monocytes of the ability to produce IL-12. These results demonstrate that LcS can
      enhance NK cell activity in vivo and in vitro in humans, and IL-12 may be
      responsible for enhancement of NK cell activity triggered by LcS.

PMID- 16968406
TI  - Nicotine inhibits the production of proinflammatory mediators in human monocytes
      by suppression of I-kappaB phosphorylation and nuclear factor-kappaB
      transcriptional activity through nicotinic acetylcholine receptor alpha7.
AB  - Macrophages/monocytes and the proinflammatory mediators, such as tumour necrosis
      factor (TNF)-alpha, prostaglandin E(2) (PGE(2)), macrophage inflammatory protein
      (MIP)-1alpha and MIP-1alpha, play a critical role in the progression of
      immunological disorders including rheumatoid arthritis, Behcet's disease and
      Crohn's disease. In addition, the nicotinic acetylcholine receptor-alpha7
      (alpha7nAChR) subunit is an essential regulator of inflammation. In this study,
      we evaluated the expression of the alpha7nAChR subunit on human peripheral
      monocytes and the effect of nicotine on the production of these proinflammatory
      mediators by activated monocytes. Fluorescein isothiocyanate (FITC)-labelled
      alpha-bungarotoxin demonstrated the cell surface expression of the alpha7nAchR
      subunit. Pretreatment with low-dose nicotine caused inhibition of TNF-alpha,
      PGE(2), MIP-1alpha and MIP-1alpha production, and mRNA expression of TNF-alpha,
      MIP-1alpha and MIP-1alpha and COX-2 in lipopolysaccharide (LPS)-activated
      monocytes. These suppressive effects of nicotine were caused at the
      transcriptional level and were mediated through alpha7nAChR. Nicotine suppressed
      the phosphorylation of I-kappaB, and then inhibited the transcriptional activity
      of nuclear factor-kappaB. These immunosuppressive effects of nicotine may
      contribute to the regulation of some immune diseases.

PMID- 16968407
TI  - Mixed inflammatory/regulatory cytokine profile marked by simultaneous raise of
      interferon-gamma and interleukin-10 and low frequency of tumour necrosis factor
      alpha(+) monocytes are hallmarks of active human visceral Leishmaniasis due to
      Leishmania chagasi infection.
AB  - Considering the complexity of the immunological events triggered during active
      visceral Leishmaniasis (VL), the relevance of the segregation of the immune
      response during human VL into type 1 and type 2 still remains unclear. For this
      purpose, in individuals living in risk areas for VL, we have evaluated especially
      asymptomatic individuals and patients with active VL, the plasmatic levels of
      cytokines and reactive nitrogen species under ex vivo conditions. In addition, we
      have also performed an analysis of intracellular cytokine patterns of circulating
      leucocytes after short-term culture, particularly in the absence of antigenic
      specific stimulation, in order to reflect dynamic events of immune response in
      vivo during Leishmania chagasi infection. Although asymptomatic individuals and
      non-infected subjects presented a similar immunological profile, an outstanding
      inflammatory/regulatory profile, based on higher plasmatic levels of cytokines
      such as interleukin (IL)-8, interferon (IFN)-gamma, tumour necrosis factor (TNF)
      alpha, IL-6 and IL-10, was associated with clinical status observed in active VL.
      In this context, we hypothesize that IL-10, through its ability to inhibit anti
      leishmanial macrophage activation, associated with the lower frequency of TNF
      alpha(+) monocytes and ordinary levels of nitrite and nitrate are the major
      mechanisms associated with disease onset.

PMID- 16968408
TI  - Both Fcgamma and complement receptors mediate transfer of immune complexes from
      erythrocytes to human macrophages under physiological flow conditions in vitro.
AB  - Abnormal clearance by the mononuclear phagocytic system of immune complexes (IC)
      is important in the pathogenesis of systemic lupus erythematosus (SLE). We have
      developed an in vitro model to investigate the cellular mechanisms involved in
      the transfer of soluble IC from erythrocytes to human macrophages under
      physiological flow conditions. In this assay, erythrocytes bearing fluorescently
      labelled IC are perfused over monolayers of human monocytes or monocyte-derived
      macrophages in a parallel-plate flow chamber, and transfer quantified using
      confocal microscopy and flow cytometry. Using aggregated human IgG as a model IC,
      we have been able to demonstrate transfer of IC from erythrocytes to macrophages.
      Blocking studies with specific neutralizing antibodies have shown that both
      complement and Fcgamma receptors are required for IC transfer. Blockade of CR4
      (alpha(x)beta(2) integrin), FcgammaRIIa or FcgammaRIII reduced transfer, while
      anti-CR3 (alpha(m)beta(2) integrin) had no effect. Blockade of CR3, FcgammaRIIa
      or FcgammaRIII also reduced the number of adhesive interactions between
      fluorescently labelled IC-bearing erythrocytes and macrophage monolayers. Taken
      together with the transfer data, this suggests differing roles for these
      receptors in the human IC transfer reaction that includes an adhesive function
      which facilitates IC processing by mononuclear phagocytes. Finally, a functional
      effect of the FcgammaRIIa R131/H131 polymorphism, important in susceptibility to
      SLE, has also been demonstrated using this model. Uptake of IgG(2) but not IgG(1)
      containing soluble IC was reduced by macrophages from individuals homozygous for
      the R131 allelic variant of the receptor.

PMID- 16968409
TI  - Activated T lymphocytes suppress osteoclastogenesis by diverting early
      monocyte/macrophage progenitor lineage commitment towards dendritic cell
      differentiation through down-regulation of receptor activator of nuclear factor
      kappaB and c-Fos.
AB  - Activated T lymphocytes either stimulate or inhibit osteoclastogenesis from
      haematopoietic progenitors in different experimental models. To address this
      controversy, we used several modes of T lymphocyte activation in osteoclast
      differentiation--mitogen-pulse, anti-CD3/CD28 stimulation and in vivo and in
      vitro alloactivation. Osteoclast-like cells were generated from non-adherent
      immature haematopoietic monocyte/macrophage progenitors in murine bone-marrow in
      the presence of receptor activator of nuclear factor (NF)-kappaB ligand (RANKL)
      and monocyte-macrophage colony-stimulating factor (M-CSF). All modes of in vivo
      and in vitro T lymphocyte activation and both CD4(+) and CD8(+) subpopulations
      produced similar inhibitory effects on osteoclastogenesis paralleled by enhanced
      dendritic cell (DC) differentiation. Osteoclast-inhibitory effect was associated
      with T lymphocyte activation and not proliferation, and could be replaced by
      their culture supernatants. The stage of osteoclast differentiation was crucial
      for the inhibitory action of activated T lymphocytes on osteoclastogenesis,
      because the suppressive effect was visible only on early osteoclast progenitors
      but not on committed osteoclasts. Inhibition was associated specifically with
      increased granulocyte-macrophage colony-stimulating factor (GM-CSF) expression by
      the mechanism of progenitor commitment toward lineages other than osteoclast
      because activated T lymphocytes down-regulated RANK, CD115, c-Fos and calcitonin
      receptor expression, and increased differentiation towards CD11c-positive DC. An
      activated T lymphocyte inhibitory role in osteoclastogenesis, confirmed in vitro
      and in vivo, mediated through GM-CSF release, may be used to counteract activated
      bone resorption mediated by T lymphocyte-derived cytokines in inflammatory and
      immune disorders. We also demonstrated the importance of alloactivation in
      osteoclast differentiation and the ability of cyclosporin A to abrogate T
      lymphocyte inhibition of osteoclastogenesis, thereby confirming the functional
      link between alloreaction and bone metabolism.

PMID- 16968410
TI  - Correlation between chemical structure and biological activities of Porphyromonas
      gingivalis synthetic lipopeptide derivatives.
AB  - We recently separated a PG1828-encoded triacylated lipoprotein (Pg-LP), composed
      of two palmitoyl and one pentadecanoyl groups at the N-terminal of
      glycerocysteine from Porphyromonas gingivalis, a periodontopathic bacteria, and
      found that Pg-LP exhibited definite biological activities through Toll-like
      receptor (TLR) 2. In the present study, we synthesized 12 different Pg-LP N
      terminal peptide moieties (PGTP) using four combinations of glyceryl (R and S)
      and cysteinyl (l and d) stereoisomers, and three different acyl group
      regioisomers, N-pentadecanoyl derivative (PGTP1), S-glycero 2-pentadecanoyl
      derivative (PGTP2) and S-glycero 3-pentadecanoyl derivative (PGTP3). All the PGTP
      compounds (RL, SL, SD, RD) tested showed TLR2-dependent cell activation. The
      activating capacities of the PGTP-R compounds were more potent than those of the
      PGTP-S compounds, whereas there were no differences between the PGTP-L and -D
      compounds. Furthermore, the production of interleukin (IL)-6 following
      stimulation with the PGTP1-RL, PGTP2-RL and PGTP3-RL compounds was impaired in
      peritoneal macrophages from TLR2 knock-out (KO), but not those from TLR1 KO or
      TLR6 KO mice. These results suggest that P. gingivalis triacylated lipopeptides
      are capable of activating host cells in a TLR2-dependent and TLR1-/TLR6
      independent manner, and the fatty acid residue at the glycerol position in the
      PGTP molecule plays an important role in recognition by TLR2.

PMID- 16968411
TI  - Cathepsins B, L and D in inflammatory bowel disease macrophages and potential
      therapeutic effects of cathepsin inhibition in vivo.
AB  - The cathepsins D (CTSD), B (CTSB) and L (CTSL) are important for the
      intracellular degradation of proteins. Increased cathepsin expression is
      associated with inflammatory diseases. We have shown previously an induction of
      CTSD expression in intestinal macrophages (IMAC) in inflamed mucosa of patients
      with inflammatory bowel disease (IBD). Here we investigated the regulation of
      CTSB and CTSL in IMAC during IBD and effects of CTSD and CTSB/CTSL inhibition in
      vivo. Human IMAC were isolated from normal and inflamed mucosa. Reverse
      transcription-polymerase chain reaction (RT-PCR) was performed for CTSB and CTSL
      mRNA. Immunostaining was used to confirm PCR results. Cathepsin inhibition was
      investigated in the dextran-sulphate-sodium (DSS) colitis model in mice with
      application of pepstatin A (CTSD inhibitor), CA-074 (CTSB inhibitor) and Z-Phe
      Tyr-aldehyde (CTSL inhibitor). CTSL mRNA was significantly up-regulated in IMAC
      isolated from IBD mucosa. Up-regulated protein expression was found mainly in
      areas of mucosal damage by immunostaining. Inhibition of CTSD in mouse DSS
      colitis was followed by an amelioration of the disease. Inhibitor-treated mice
      showed a significant lower histological score (HS) and less colon reduction in
      comparison to controls. Similarly, simultaneous inhibition of CTSB/CTSL was
      followed by a significant amelioration of colitis. Expression of tissue-degrading
      cathepsins is increased in IMAC in IBD. Inhibition of CTSD as well as CTSB/CTSL
      is followed by an amelioration of experimental colitis. The prevention of mucosal
      damage by cathepsin inhibition could represent a new approach for the therapy of
      IBD.

PMID- 16968413
TI  - Cardiovascular pharmacology and physiology of the isoprostanes.
AB  - F(2)-isoprostanes are a complex family of compounds produced from arachidonic
      acid via a free radical-catalyzed mechanism. Their quantification as a
      pathophysiological biomarker provides a unique opportunity to investigate lipid
      peroxidation in vascular diseases. Their measurement also provides an interesting
      biomarker for the rational dose selection of antioxidants in vascular diseases
      where oxidative stress might be involved. In addition to their use as biomarkers,
      some isoprostanes possess a biological activity. The 15-series F(2)- and E(2)
      isoprostanes mediate vasoconstriction in different vascular beds and species. In
      addition, 15-F(2t)-IsoP induces smooth muscle cells mitogenesis and monocyte
      adhesion to endothelial cells. The data available supports but does not prove the
      hypothesis that isoprostanes are involved in vascular physiology and
      pathogenesis.

PMID- 16968412
TI  - Role of Th1-stimulating cytokines in bacillus Calmette-Guerin (BCG)-induced
      macrophage cytotoxicity against mouse bladder cancer MBT-2 cells.
AB  - Previously, we have demonstrated that macrophages exhibited cytotoxicity toward
      mouse bladder cancer MBT-2 cells upon bacille Calmette-Guerin (BCG) stimulation.
      In this study, we have investigated the role of Th1-stimulating cytokines in BCG
      induced macrophage cytotoxicity. Thioglycollate-elicited peritoneal exudate cells
      (PECs) were used as a conventional source for macrophages and the induction of
      PEC effector functions (cytolytic activity and cytokine production) by BCG was
      evaluated in vitro. The BCG-activated PECs showed potent cytotoxicity and killed
      MBT-2 cells in a dose-dependent manner. Depletion of T cells, natural killer (NK)
      cells, or both, in PEC preparations exhibited a marginal or small reduction of
      MBT-2 cell killing, suggesting that macrophages played a primary role in PEC
      cytotoxicity. Transwell assays indicated that the maximal PEC cytotoxicity
      required both direct cell-cell contact and soluble factors such as interferon
      (IFN)-gamma and tumour necrosis factor (TNF)-alpha. Neutralizing endogenous
      cytokines interleukin (IL)-12, IL-18, IFN-gamma or TNF-alpha reduced PEC
      cytotoxicity by 38%, 22%, 15% and 94%, respectively. Supplementation of BCG with
      recombinant (r)IL-2, rIL-12 or rIL-18 increased PEC cytotoxicity by approximately
      twofold. Compared with control BCG for PEC stimulation, rBCGs expressing IL-2 or
      IL-18 showed enhanced MBT-2 cell killing by PECs. Increased cytokine production
      (IFN-gamma, TNF-alpha and IL-6) was also observed in rBCG-stimulated PEC
      cultures. Taken together, these results suggest that Th1-stimulating cytokines
      play an important role in BCG-induced macrophage cytotoxicity and that
      combination of BCG with selected Th1-stimulating cytokines, either supplemented
      or expressed by BCG, may enhance the effect of BCG in the treatment of bladder
      cancer patients.

PMID- 16968414
TI  - Regulation of inflammation by PPARs: a future approach to treat lung inflammatory
      diseases?
AB  - Lung inflammatory diseases, such as acute lung injury (ALI), asthma, chronic
      obstructive pulmonary disease (COPD) and lung fibrosis, represent a major health
      problem worldwide. Although glucocorticoids are the most potent anti-inflammatory
      drug in asthma, they exhibit major side effects and have poor activity in lung
      inflammatory disorders such as ALI or COPD. Therefore, there is growing need for
      the development of alternative or new therapies to treat inflammation in the
      lung. Peroxisome proliferator-activated receptors (PPARs), including the three
      isotypes PPARalpha, PPARbeta (or PPARdelta) and PPARgamma, are transcription
      factors belonging to the nuclear hormone receptor superfamily. PPARs, and in
      particular PPARalpha and PPARgamma, are well known for their critical role in the
      regulation of energy homeostasis by controlling expression of a variety of genes
      involved in lipid and carbohydrate metabolism. Synthetic ligands of the two
      receptor isotypes, the fibrates and the thiazolidinediones, are clinically used
      to treat dyslipidaemia and type 2 diabetes, respectively. Recently however,
      PPARalpha and PPARgamma have been shown to exert a potent anti-inflammatory
      activity, mainly through their ability to downregulate pro-inflammatory gene
      expression and inflammatory cell functions. The present article reviews the
      current knowledge of the role of PPARalpha and PPARgamma in controlling
      inflammation, and presents different findings suggesting that PPARalpha and
      PPARgamma activators may be helpful in the treatment of lung inflammatory
      diseases.

PMID- 16968415
TI  - Effects of chronic trimetazidine treatment on myocardial preconditioning in
      anesthetized rats.
AB  - Trimetazidine is a widely used anti-ischemic agent, but effects of its chronic
      treatment on myocardial preconditioning in anesthetized animals have not been
      investigated. The aim of this study was to examine the effects of 15-day
      treatment of trimetazidine on ischemic preconditioning and carbachol-induced
      preconditioning in anesthetized rats. Ischemic preconditioning, induced by 5 min
      of coronary artery occlusion and 5 min of reperfusion, significantly decreased
      the total number of ventricular ectopic beats, the incidence of ventricular
      tachycardia and abolished the occurrence of ventricular fibrillation (VF) during
      30 min of ischemia. Trimetazidine (10 mg/kg/day, i.p. for 15 days and 10 mg/kg,
      i.v.) itself attenuated these arrhythmia parameters with no marked effect on
      hemodynamic effects. In the presence of trimetazidine, anti-arrhythmic effects of
      ischemic preconditioning were present. Carbachol infusion induced preconditioning
      with a marked depression of mean arterial blood pressure, heart rate and the
      total number of ventricular ectopic beats. No VF was observed in carbachol
      induced preconditioning. The marked reductions in arrhythmia parameters that
      induced carbachol-induced preconditioning were also preserved in the presence of
      trimetazidine. Arrhythmia scores and myocardial infarct size were reduced
      significantly with ischemic preconditioning or carbachol-induced preconditioning
      and were not modified by trimetazidine. Lactate and malondialdehyde levels were
      suppressed significantly with preconditioning or trimetazidine + preconditioning
      groups. These results show that chronic treatment of trimetazidine protects the
      heart against ischemia-induced arrhythmias, reduces myocardial infarct size,
      plasma lactate and malondialdehyde levels, and preserves the effects of ischemic
      and pharmacological preconditioning in anesthetized rats.

PMID- 16968416
TI  - Involvement of endogenous opioid peptides and nitric oxide in the blunted
      chronotropic and inotropic responses to beta-adrenergic stimulation in cirrhotic
      rats.
AB  - It is well known that chronotropic and inotropic responses to beta-adrenergic
      stimulation are impaired in cirrhosis, but the exact reason is not clear.
      Considering the inhibitory effect of endogenous opioid peptides and nitric oxide
      (NO) on beta-adrenergic pathway, we examined their roles in hyporesponsiveness of
      isolated atria and papillary muscles to isoproterenol stimulation in cirrhotic
      rats. Cirrhosis was induced by chronic bile duct ligation. Four weeks after
      ligation or sham operation, the responses of the isolated atria and papillary
      muscles to isoproterenol stimulation were evaluated in the absence and presence
      of naltrexone HCl (10(-6) m), N(omega)-nitro-L-arginine methyl ester (L-NAME, 10(
      4) m), and naltrexone plus L-NAME in the organ bath. Considering the role of
      inducible NOS (iNOS) in hemodynamic abnormalities of cirrhotic rats, the
      chronotropic and inotropic responses of cirrhotic rats to isoproterenol
      stimulation were also assessed in the presence of aminoguanidine (a selective
      inhibitor of iNOS, 3 x 10(-4) m). Sham operation had no significant effect on
      basal atrial beating rate, contractile force, and maximal time derivatives for
      the development and the dissipation of papillary muscle tension. The basal atrial
      beating rate of cirrhotic rats did not show any significant difference compared
      with the sham-operated ones; however, the basal contractile parameters were
      significantly decreased in cirrhosis. Although the maximum effects of
      isoproterenol on chronotropic and inotropic responses were significantly reduced
      in cirrhotic rats, there was no difference in half-maximal effective
      concentrations of isoproterenol in these concentration-response curves. The basal
      abnormalities and the attenuated chronotropic and inotropic responses to
      isoproterenol were completely corrected by the administration of naltrexone, L
      NAME and aminoguanidine. Concurrent administration of naltrexone and L-NAME also
      restored to normal the basal abnormalities and the blunted responses to
      isoproterenol in cirrhotic rats, and did not show any antagonistic effect. Based
      on these findings, both the endogenous opioid peptides and NO may be involved in
      the attenuated chronotropic and inotropic responses to beta-adrenergic
      stimulation in cirrhosis. It seems that the iNOS activity results in NO-induced
      hyporesponsiveness to beta-adrenergic stimulation in cirrhosis.

PMID- 16968417
TI  - Effect of cooling on the responses of human saphenous vein to fentanyl,
      remifentanil and sufentanil.
AB  - We studied the vasodilatory effects of fentanyl, remifentanil and sufentanil on
      the human saphenous vein strips at 37, 32 and 28 degrees C. Fentanyl produced
      concentration-dependent relaxation of human saphenous vein strips precontracted
      with 5-hydroxytryptamine (5-HT) at every temperature studied. Compared with vein
      strips at 37 degrees C, relaxant responses to each one concentration of fentanyl
      were significantly reduced at 32 and 28 degrees C. Remifentanil relaxed vein
      strips in a concentration-dependent way and the relaxation for all concentrations
      were significantly greater at 32 and 28 degrees C compared with 37 degrees C.
      Sufentanil produced concentration-dependent relaxation in saphenous vein strips
      precontracted with 5-HT. These relaxant responses were similar at 32 degrees C
      compared with 37 degrees C. When bath temperature was lowered from 37 to 28
      degrees C, the relaxant responses to sufentanil were significantly reduced. In
      summary, the present study suggests that cooling reduces the relaxation caused by
      fentanyl and sufentanil on human saphenous veins but augments the relaxation with
      remifentanil. The augmented vasodilatory effect of remifentanil with cooling may
      be useful on systemic vascular resistance and organ preservation under
      hypothermic conditions like cardiopulmonary bypass surgery.

PMID- 16968418
TI  - Metabolic normalization of alpha-ketoglutarate against N-nitrosodiethylamine
      induced hepatocarcinogenesis in rats.
AB  - Chemoprevention of cancer is one of the reliable approaches to control the
      incidence of cancer. In the present study, we investigated the chemopreventive
      role of alpha-ketoglutarate (alpha-KG) during N-nitrosodiethylamine (NDEA)
      induced hepatocarcinogenesis. The activities of serum aspartate and alanine
      transaminases were found to be significantly higher in NDEA + CCl(4)-treated
      animals when compared with control animals. Administration of alpha-KG restored
      the activities of transaminases to near normal range. The levels of lipid
      peroxides, thiobarbituric acid reactive substances were decreased in the liver
      tissue of NDEA + CCl(4)-treated animals when compared with control animals. alpha
      KG reversed the lipid peroxide levels to near normal range. Levels of
      antioxidants, reduced glutathione and activities of its dependent enzymes,
      glutathione peroxidase and glutathione-S-transferase were found to be
      significantly higher in liver tissue of NDEA + CCl(4)-treated animals when
      compared with control animals. alpha-KG administration positively modulated the
      antioxidant levels to near normal range. In conclusion, it can be suggested that
      alpha-KG exerts chemopreventive role which may attributable to its ability to
      positively modulate the transaminase activities and oxidant-antioxidant imbalance
      during hepatocarcinogenesis.

PMID- 16968419
TI  - Attenuation of ethanol withdrawal syndrome by extract of Hypericum perforatum in
      Wistar rats.
AB  - The effects of Hypericum perforatum (St John's wort) on ethanol withdrawal
      syndrome have been investigated in ethanol-dependent rats. Adult male Wistar rats
      were subjects. Ethanol (7.2% v/v) was given to rats by a liquid diet for 15 days.
      Hypericum perforatum extract (HPE) (25-200 mg/kg) and saline were injected to
      rats intraperitoneally just before ethanol withdrawal. After second, fourth and
      sixth hour of ethanol withdrawal, rats were observed for 5 min, and withdrawal
      signs that included locomotor hyperactivity, stereotyped behavior and tremors
      were recorded or rated. A second series of injections was given at 6 h after the
      first one, and subjects were then tested for audiogenic seizures. HPE (25-200
      mg/kg) produced some dose-dependent and significant inhibitory effects on
      locomotor hyperactivity at second and sixth hour of ethanol withdrawal. In
      addition, it significantly reduced the number of stereotyped behaviors at the
      same dose range. HPE (50 and 100 mg/kg) produced some significant inhibitory
      effects on tremor and audiogenic seizures during withdrawal period. These results
      suggest that HPE has some beneficial effects on ethanol withdrawal syndrome in
      rats.

PMID- 16968420
TI  - The effect of positive end-expiratory pressure ventilation on propofol
      concentrations during general anesthesia in humans.
AB  - The present study investigated the effects of positive end-expiratory pressure
      (PEEP) on propofol concentrations in humans. Eleven patients undergoing elective
      surgery were enrolled in this study. Anesthesia was induced with propofol, then
      maintained using 60% nitrous oxide in oxygen, fentanyl 10-20 microg/kg and
      continuous infusion of propofol. Vecuronium was used to facilitate the artificial
      ventilation of the lungs. Propofol was administered to all subjects via target
      controlled infusion to achieve a propofol concentration of 6.0 microg/mL at
      intubation and 2.0 microg/mL after intubation. Before, during and after PEEP
      level of 10 cmH(2)O, cardiac output (CO) and effective liver blood flow (LBF) was
      measured using indocyanine green as an indicator and blood propofol concentration
      was determined using high-performance liquid chromatography. Data are expressed
      as median and range. After PEEP of 10 cmH(2)O was applied, CO and effective LBF
      was significantly decreased from 5.5 (3.8-6.8) L/min to 4.5 (3.2-5.8) L/min (P <
      0.05), 0.78 (0.65-1.21) L/min to 0.65 (0.50-0.89) L/min (P < 0.05), respectively.
      Propofol concentration was significantly increased from 2.21 (1.46-2.63)
      microg/mL to 2.45(1.79-2.89) microg/mL (P < 0.05). These data indicate that
      propofol concentrations can be increased by PEEP, suggesting the possibility of
      overdosing following PEEP.

PMID- 16968421
TI  - Comparison of two epoetin brands in anemic hemodialysis patients: results of two
      efficacy trials and a single-dose pharmacokinetic study.
AB  - Epoetin alpha is recombinant human erythropoietin with established efficacy and
      safety in the treatment of renal anemia. Epoetin omega is recombinant
      erythropoietin that differs from epoetin alpha in the sugar moiety. We compared
      the two epoetins in two 12-week efficacy studies (S1, S2) with twice-weekly
      dosing, and a single-dose crossover pharmacokinetic (PK) study in severely anemic
      hemodialysis patients. Epoetins were delivered subcutaneously in all studies. S1
      was randomized (omega n = 39, alpha n = 38), while S2 included the patients from
      S1 (omega n = 32, alpha n = 24) with 'switched' treatments (omegaleft arrow over
      right arrowalpha). In the intent-to-treat analysis, average weekly difference in
      hemoglobin vs. the baseline value was higher in omega-treated patients in both
      studies: 1.94 +/- 0.81 vs. 1.23 +/- 0.62 g/dL in S1 and 1.44 +/- 0.72 vs. 0.95 +/
      0.62 g/dL in S2. The unadjusted and adjusted omega-alpha differences in S1 were
      0.71 g/dL (95% CI 0.38-1.04; P < 0.001) and 0.78 g/dL (95% CI 0.49-1.08; P <
      0.001), respectively. Differences in S2 were 0.48 g/dL (95% CI 0.11-0.86; P =
      0.012) and 0.46 g/dL (95% CI 0.1-0.82; P = 0.025), unadjusted and adjusted,
      respectively. Average weekly epoetin dose was lower in the omega groups in both
      studies: 87 +/- 25 vs. 108 +/- 21 IU/kg in S1 and 106 +/- 25 vs. 125 +/- 20 IU/kg
      in S2. The unadjusted and adjusted omega-alpha differences in S1 were -21 IU/kg
      (95% CI -32 to -11; P < 0.001) and -24 IU/kg (95% CI -35 to -13; P < 0.001),
      respectively. Differences in S2 were -19 IU/kg (95% CI -31 to -6; P = 0.006) and 
      15 IU/kg (95% CI -28 to -2; P = 0.04), unadjusted and adjusted, respectively. In
      the PK study (n = 17), the peak and total exposure to epoetin after 50 IU/kg of
      either drug was approximately twice greater for epoetin omega: C(max) omega/alpha
      2.19 (95% CI 1.55-3.11), AUC omega/alpha 2.24 (95% CI 1.64-3.06). Epoetins were
      comparably well tolerated. In hemodialysis patients, subcutaneous epoetin omega
      apparently provides greater bioavailability and anti-anemic effect per
      administered dose (IU) than epoetin alpha.

PMID- 16968422
TI  - Chronic treatment with trimetazidine reduces the upregulation of atrial
      natriuretic peptide in heart failure.
AB  - Trimetazidine (TMZ) is effective for the treatment of ischemic cardiomyopathy;
      however, little is known about the effect of TMZ in established injury-induced
      heart failure. When rats with established infarct-induced heart failure were
      treated for 12 weeks with TMZ there was no effect on left ventricular function or
      dilation, or on mRNA expression of fatty acid oxidation enzymes. On the other
      hand, TMZ significantly reduced atrial natriuretic peptide mRNA levels compared
      with untreated rats.

PMID- 16968423
TI  - The use of clinical vignettes to study nursing.

PMID- 16968424
TI  - Mealtimes in hospital: when will we ever learn?

PMID- 16968425
TI  - Experiences of African nurses in the UK National Health Service: a literature
      review.
AB  - AIM: This review aims to highlight the experiences of black African nurses in the
      United Kingdom. BACKGROUND: There is an acute shortage of trained nurses in the
      United Kingdom, which has occurred because of several factors including ageing of
      the nurse population and increasing demand due to an ageing population as well as
      under investment in nurse education during the 1980s. Government initiatives have
      included recruiting nurses trained overseas to meet present and future demands.
      Among these internationally recruited nurses, a large number came from Africa,
      but little is known about the experience of nurses once they are in the United
      Kingdom. Although it is known that ethnic minority nurses suffer discrimination
      in the National Health Service, experiences of internationally recruited nurses
      and nurses from African countries, in particular, merit attention as their
      nursing practices and culture in general are different from those of developed
      countries. METHODS: A literature search was conducted using CINAHL, Medline and
      Cochrane databases by using the following terms in various combinations:
      Experiences, African nurses, international nurses, ethnic minorities,
      discrimination, equal opportunities, United Kingdom and NHS. CONCLUSIONS: There
      is very little research into the experiences of African nurses in the United
      Kingdom. Research has concentrated on the experience of internationally recruited
      nurses and ethnic minority nurses in general. There is agreement that most
      foreign nurses have a negative experience of working in the United Kingdom.
      Nurses face discrimination in pay and conditions of service and most are
      exploited by managers. There are also ethical questions surrounding the
      recruitment of nurses form developing countries and their treatment once they
      come to the United Kingdom. RELEVANCE TO CLINICAL PRACTICE: As the nursing
      workforce in the United Kingdom becomes increasingly diverse through
      international recruitment, it is important to have knowledge of experiences of
      different groups of nurses. This helps to devise adaptation programs for smooth
      transition tailored to particular groups and training that will help United
      Kingdom nurses to work in harmony with their foreign colleagues.

PMID- 16968426
TI  - Mealtimes in hospital--who does what?
AB  - AIM: This paper describes the findings of a descriptive study about what nurses
      do at mealtimes in relation to monitoring/assisting the eating practices of older
      patients in an acute care facility. BACKGROUND: The prevalence of under nutrition
      is known to be high in hospitalized older patients and insufficient dietary
      intake is regarded as a major cause. However, most of the research tends to
      concentrate on the nursing home setting. Little is known about the situation in
      acute care facilities. METHODS: Two medical wards participated in the study. Ward
      1 had introduced a change of nurses' meal break time and ward 2 continued with
      normal practice. Convenience sampling was used. Fifty nurses and 48 patients were
      observed at different mealtimes during two weeks. Four nurses and four patients
      who were observed were also interviewed. Data were analysed using descriptive
      statistics and thematic analysis. RESULTS: Kitchen staff delivered all meals and
      collected the majority of the meal trays. Older patients did not receive enough
      assistance during mealtimes. Interruptions happened frequently and social
      interaction was neglected. About one-third of patients observed left more than
      two-third of their meals. CONCLUSION: Nutrition issues appeared to receive less
      priority in the ward than other nursing care activities and nurses' assistance
      was generally insufficient and not provided in a timely manner. Relevance to
      clinical practice. Findings highlight the deficiency in practice that should
      suggest to nurses that they examine their practice and put into place strategies
      to ensure older patients are properly/adequately hydrated and receive sufficient
      nutrient intake.

PMID- 16968427
TI  - The health beliefs of hospital staff and the reporting of needlestick injury.
AB  - AIM: The aim of this study is to examine the connection between the health
      beliefs of hospital staff (doctors, nurses and auxiliary staff) and their failure
      to report needlestick injuries. BACKGROUND: Needlestick injury to hospital staff
      is quite frequent and can result in infections and disease, but staff frequently
      do not report the injury despite their awareness of the risk of blood-borne
      pathogens. METHODS: Five questionnaires were constructed based on three existing
      research tools and were tested for validity and reliability. Two hundred and
      forty questionnaires were distributed to eight randomly chosen departments of a
      single Israeli hospital. Seventy-six percent of the questionnaires were
      anonymously completed and returned. RESULTS: Nurses had the highest rate of
      needlestick injury, followed by auxiliary staff and doctors. Auxiliary staff
      showed the highest rate of compliance with the duty to report such injuries,
      while doctors showed the lowest. Perceived severity of contractable disease, the
      perceived efficacy of reporting injuries and overall motivation to maintain
      health were the best predictors of reporting compliance. Non-compliers emphasized
      the negative aspects of reporting the injuries, primarily that it took up too
      much time. CONCLUSIONS: The solution to non-compliance with the duty to report
      must be a targeted investment in training and education. Relevance to clinical
      practice. Finding the reasons for compliance and non-compliance with the duty to
      report needlestick injuries will help in designing educational programmes for
      hospital staff and in determining a strategy for improving health behaviour.

PMID- 16968429
TI  - Student nurses' experiences of caring for infectious patients in source
      isolation. A hermeneutic phenomenological study.
AB  - AIM: To illuminate issues central to general student nurses' experiences of
      caring for isolated patients within the hospital environment, which may assist
      facilitators of learning to prepare students for caring roles. BACKGROUND:
      Because of the development of hospital-resistant micro-organisms, caring for
      patients in source isolation is a frequent occurrence for supernumerary students
      on the general nursing programme. Despite this, students' perceptions of caring
      for this client group remain under researched. DESIGN AND METHODS: Through
      methods grounded in hermeneutic phenomenology, eight students in the second year
      of the three-year undergraduate programme in general nursing were interviewed
      using an un-structured, open-ended and face-to-face interview approach. Data
      analysis was approached through thematic analysis. RESULTS: Four themes emerged:
      The organization: caring in context, Barriers and breaking the barriers, Theory
      and practice, Only a student. The imposed physical, psychological, social and
      emotional barriers of isolation dramatically alter the caring experience.
      Balancing the care of isolated patients to meet their individual needs while
      preventing the spread of infection has significance for students. Applying
      infection control theory to the care of patients in source isolation is vital for
      students' personal and professional development. Perceptions of supernumerary
      status influence students' experiences of caring for these patients. RELEVANCE TO
      CLINICAL PRACTICE: Designating equipment for the sole use of isolated patients
      assists students in maintaining infection control standards. Balancing the art
      and science of caring for patients in source isolation is important to reduce
      barriers to the student-patient relationship and to promote delivery of holistic
      care. Staff nurses should consider using available opportunities to impart
      recommended isolation practices to students thereby linking the theory of
      infection control to patient care. Providing structured, continuing education for
      all grades of staff would acknowledge the interdependence of all healthcare
      workers in controlling hospital-acquired infection.

PMID- 16968428
TI  - Satisfied patients are also vulnerable patients--narratives from an acute care
      ward.
AB  - AIM: To illuminate the experience of being a patient and cared for in an acute
      care ward. BACKGROUND: Patients may be the best source of information for
      assessing the quality of care in acute care wards. Studies often show that
      patients' satisfaction with their hospital stay is interpreted by managers and
      care providers as a measure for quality of care. DESIGN: Ten patients were
      interviewed as part of a comprehensive investigation by four researchers into the
      narratives of five enrolled nurses (study No. 1--published in Nursing Ethics
      2004), five Registered Nurses (study No. 2 published in Nursing Ethics 2005) and
      10 patients (study No. 3) about their experiences from an acute care ward at one
      university hospital in Sweden. METHOD: A phenomenological hermeneutical method
      (inspired by the French philosopher Paul Ricoeur) was conducted in all three
      studies. FINDINGS: The patients are very satisfied with their treatment and care.
      They also tell about factors that they do not consider as optimal, but which they
      explain as compromises, which must be accepted as a necessary part of their stay
      in the ward. This study demonstrates a close connection between patient
      satisfaction and vulnerability. CONCLUSIONS: It is important for all health care
      providers not to be complacent and satisfied when patients express their
      satisfaction with their treatment and care. This can result in losing the focus
      on the patients' vulnerability and existential thoughts and reflections which are
      difficult for them, and which need to be addressed. RELEVANCE TO CLINICAL
      PRACTICE: The findings can be seen as a challenge for the health care providers
      as well as the organization to provide quality of care to patients in acute care
      ward. When listening to the patients' voice it makes it easier to be aware of the
      content of their vulnerability.

PMID- 16968430
TI  - The culture of a trauma team in relation to human factors.
AB  - AIM: The aim of this ethnographic study was to explore the culture of a trauma
      team in relation to human factors. BACKGROUND: Traumatic injury is the leading
      cause of death in the first four decades of life in the western world. Evidence
      suggests that the initial assessment and resuscitation of trauma victims is most
      successfully carried out by an organized trauma team. Most trauma teams use
      Advanced Trauma Life Support principles which focus on rapid assessment and
      management of the patient's injuries. Similarly, most trauma education focuses on
      Advanced Trauma Life Support principles, concentrating firmly on the patient's
      physical status. Nevertheless, contemporary literature about emergency teams
      suggests that human factors, such as communication and interprofessional
      relationships, can affect the team's performance regardless of how clinically
      skilled the team members are. METHOD: Focused ethnography was used to explore the
      culture of a trauma team in one teaching hospital. Six periods of observation
      were undertaken followed by 11 semi-structured interviews with purposively chosen
      key personnel. Data from transcripts of the observation field notes and
      interviews were analysed using open coding, followed by formation of categories
      resulting in the emergence of six central categories. RESULTS: Findings suggest
      that leadership, role competence, conflict, communication, the environment and
      the status of the patient all influence the culture of the trauma team.
      Interpretation of these categories suggests that trauma team education should
      include human factor considerations such as leadership skills, team management,
      interprofessional teamwork, conflict resolution and communication strategies.
      RELEVANCE FOR CLINICAL PRACTICE: The findings suggest that support systems for
      role development of junior team leaders should be formalized. The proven airline
      industry techniques of Crew Resource Management, focusing on teamwork and
      effective communication, could be implemented into continuing professional
      development for trauma teams to engender collaboration and interprofessional
      practice.

PMID- 16968431
TI  - Effectiveness of sleep management strategies for residents of aged care
      facilities: findings of a systematic review.
AB  - AIMS AND OBJECTIVES: The objectives of this systematic review were to determine
      the most effective tools for the assessment and diagnosis of sleep problems, as
      well as identify the most effective strategies for the promotion of sleep within
      this population. BACKGROUND: Experiencing reduced sleep quality is often
      associated with normal ageing, however this may be exacerbated for residents of
      aged care facilities. External factors such as noise, light and night-time
      nursing may impact negatively upon sleeping patterns. METHODS: Eleven electronic
      databases and the reference lists and bibliographies of included studies were
      searched. Papers were grouped according to type of intervention or assessment
      tool and presented in a narrative summary. CONCLUSIONS: The review identified
      many interventions to promote sleep. Multidisciplinary strategies such as
      combining a reduction in environmental noise, reduction of night-time nursing
      care and promotion of daytime activity, are likely to be most effective for
      promoting sleep in the population of interest. The use of sedating medications is
      cautioned, as their long-term efficacy in promoting sleep is questionable. Wrist
      actigraphy was found to be the most accurate objective sleep assessment tool.
      RELEVANCE TO CLINICAL PRACTICE: Lack of sleep, disturbed sleep and the overuse of
      medications especially sedations reduce the quality of life for older people.
      Effective, safe sleep interventions should be promoted and practised by nurses.

PMID- 16968432
TI  - Do nurses promote urinary continence in hospitalized older people?: An
      exploratory study.
AB  - AIM: The aim of this paper is to explore whether nurses working in elderly
      medicine and in acute medical settings promote urinary continence in older people
      or in reality use containment strategies. BACKGROUND: Untreated urinary
      incontinence in older adults can result in prolonged hospital admission and
      increased risk of admission to long-term care. Urinary incontinence can also have
      severe psychosocial effects on older people. Most studies relating to this topic
      have relied on quantitative approaches to data collection with a seeming lack of
      qualitative investigation into how nursing staff promote urinary continence in
      hospitalized older people. METHOD: Focus groups and one-to-one semi-structured
      interviews were carried out in two NHS regions in Scotland. Registered and non
      Registered Nurses were invited to participate. Five focus groups (n = 17) and
      four single interviews (n = 4) were conducted. Data generated were analysed
      thematically using QSR N-VIVO 2. FINDINGS: Some nurses believe that older people
      accept urinary incontinence as a consequence of ageing. Lack of assessment
      results in older people being labelled as incontinent of urine. Assessment
      strategies in medicine for the elderly tend to focus on product identification
      and management of incontinence. Although nurses from all clinical areas identify
      the importance of promoting continence, the problem continues to be contained
      rather than treated. Conflicting clinical priorities, varying staff approaches to
      urinary continence and deficits in education are cited among the barriers to
      promoting continence. CONCLUSIONS: The results suggest that nurses continue to
      contain urinary incontinence rather than promoting continence in older people.
      RELEVANCE TO CLINICAL PRACTICE: Nursing staff need to be aware of the impact of
      untreated urinary incontinence on older people. Practitioners should promote
      continence rather than employing containment strategies. A validated assessment
      tool for older people needs to be developed. Views of older people should be
      sought regarding their attitudes towards urinary incontinence.

PMID- 16968433
TI  - Determining factors that have an impact upon effective evidence-based pain
      management with older people, following colorectal surgery: an ethnographic
      study.
AB  - AIM: The aim of this project was to examine pain management practices with older
      people admitted to the colorectal unit of an acute hospital trust. BACKGROUND:
      Although pain assessment and management are judged to be a priority, little
      research has examined the care older people receive in the acute surgical
      setting. Thus, pain in older people (65 years and over) can be under recognized
      and unrelieved. With the number of older people requiring surgery increasing, it
      is important to identify factors in the practice context that enhance or inhibit
      effective pain management. DESIGN: The project drew upon an in-depth ethnographic
      approach. METHOD: Sixty-two hours of around the clock, non-participant
      observation of nursing practice was completed. Thirty-nine (78%) nurses and forty
      six (42%) patients were observed. Seven (6%) additional patients participated in
      pre- and postoperative interviews and 35 (90%) nurses completed the Nursing Work
      Index--Revised Questionnaire. FINDINGS: Holistic pain assessment for older people
      was found to be deficient in the acute surgical setting. Nurses appeared unaware
      of the importance of addressing the particular pain needs of older patients.
      Inflexible analgesic prescriptions provided the mainstay treatment of pain, with
      minimal consideration given to non-pharmacological strategies. Older people
      wanted to be active participants in their care. However, existing pain management
      practices disempowered older patients, making them reluctant or unable to discuss
      their pain with ward staff. CONCLUSION: Comprehensive pain assessment, improved
      documentation and proficient communication, inclusive of older patients, are
      necessary to improve pain management practices. It is imperative that patients,
      nurses, doctors and Acute Pain Service work in collaboration to challenge pain
      management practices and implement change. RELEVANCE TO CLINICAL PRACTICE: The
      project demonstrated some of the multiple and complex factors that affect the
      older persons' pain experience and identified three action research cycles for
      further development work.

PMID- 16968434
TI  - The patient's vulnerability, dependence and exposed situation in the discharge
      process: experiences of district nurses, geriatric nurses and social workers.
AB  - AIM: The aim of the study was to obtain a deeper understanding of the experiences
      of the discharge process among different professionals. BACKGROUND: An optimal
      discharge process for hospitalized elderly to other forms of care is of crucial
      importance, especially since health and medical policies encourages shorter
      hospital stays and increased healthcare service in outpatient care. METHODS:
      Nurses and social workers from inpatient care, outpatient care, municipal care
      and social services were interviewed. Eight focus-group interviews with a total
      of 31 persons were conducted. The subsequent analyses followed a phenomenological
      approach. RESULTS: The findings revealed three themes, Framework, Basic Values
      and Patient Resources, which influenced the professionals' actions in the
      discharge process. The overall emerging structure comprised the patient's
      vulnerability, dependence and exposed situation in the discharge process.
      CONCLUSION: In conclusion some factors are of special importance for the co
      operation and the actions of professionals involved in the discharge process.
      Firstly, a distinct and common framework, with conscious and organizationally
      based values. Secondly the need to take the patient resources into consideration.
      Together these factors could contribute to secure the patients involvement in the
      discharge process and to design an optimal, safe and good care. RELEVANCE TO
      CLINICAL PRACTICE: Collaborative approaches among a range of professionals within
      a variety of organizations are common, especially in the care of the elderly. The
      role and support of both the organizations and the educational units are decisive
      factors in this area.

PMID- 16968435
TI  - Negotiation of parental roles within family-centred care: a review of the
      research.
AB  - AIMS AND OBJECTIVES: To review research published in the past 15 years about how
      children's nurses' negotiate with parents in relation to family-centred care.
      BACKGROUND: Family-centred care is a basic tenet of children's nursing and
      requires a process of negotiation between health professionals and the family,
      which results in shared decision-making about what the child's care will be and
      who will provide this. The literature highlights inconsistencies in the degree to
      which nurses are willing to negotiate with parents and allow them to participate
      in decisions regarding care of their child. There is need to explore further the
      extent to which nurses communicate and negotiate shared care with children and
      their parents. CONCLUSIONS: Three themes emerged from this review of the
      literature relating to whether role negotiation occurred in practice, parental
      expectations of participation in their child's care and issues relating to power
      and control. Parents wanted to be involved in their child's care but found that
      nurses' lack of communication and limited negotiation meant that this did not
      always occur. Nurses appeared to have clear ideas about what nursing care parents
      could be involved with and did not routinely negotiate with parents in this
      context. RELEVANCE TO CLINICAL PRACTICE: For family-centred care to be a reality
      nurses need to negotiate and communicate with children and their families
      effectively. Parents need to be able to negotiate with health staff what this
      participation will involve and to negotiate new roles for themselves in sharing
      care of their sick child. Parents should be involved in the decision-making
      process. However, research suggests that a lack of effective communication,
      professional expectations and issues of power and control often inhibit open and
      mutual negotiation between families and nurses.

PMID- 16968436
TI  - Family centred care: a review of qualitative studies.
AB  - AIM: To review systematically qualitative studies, which were found during a
      literature search for a Cochrane systematic review of the use of family centred
      care in children's hospitals. BACKGROUND: Family centred care has become a
      cornerstone of paediatric practice, however, its effectiveness is not known. No
      single definition exists, rather a list of elements that constitute family
      centred care. However, it is recognized to involve the parents in care planning
      for a child in health services. A new definition is presented here. METHODS: The
      papers were found in wide range of databases, by hand searching and by contacting
      the authors where necessary, using terms given in detail in the protocol in the
      Cochrane Library, in 2004. Qualitative studies could not be used for statistical
      analysis, but are still important to the review and so are described separately
      in this paper. RESULTS: Negotiation between staff and families, perceptions held
      by both parents and staff roles influenced the delivery of family centred care. A
      sub-theme of cost of family centred care to families and staffs was discovered
      and this included both financial and emotional costs. CONCLUSION: Further
      research is needed to generate evidence about family centred care in situations
      arising from modern models of care in which family centred care is thought to be
      an inherent part, but which leave families with the care of sick children with
      little or no support. RELEVANCE TO CLINICAL PRACTICE: Family centred care is said
      to be used widely in practice. More research is needed to ensure that is it being
      implemented correctly.

PMID- 16968437
TI  - How do children's nurses make clinical decisions? Two preliminary studies.
AB  - AIMS AND OBJECTIVES: To gain an understanding of how children's nurses make
      clinical decisions. BACKGROUND: Several studies have explored how nurses make
      clinical decisions and the factors that may affect the decision-making strategies
      used. However, the results of these studies are contradictory. Further, little is
      known about children's nurses' decision-making strategies. DESIGN: The think
      aloud technique. METHODS: Nurses (n = 12) from three surgical wards and nurses (n
      = 15) from three medical wards in a Scottish children's hospital were presented
      with clinical scenarios and asked to think aloud. The verbal protocols were
      analysed to provide an indication of how children's nurses made decisions.
      Whether there were any differences in decision-making between experienced and
      less experienced nurses and between graduates and non-graduates was also
      explored. RESULTS: Analysis of verbal protocols obtained using the think aloud
      technique suggested that all the nurses in the sample used a hypothetico
      deductive (analytical) model of decision-making. Further, all participants
      appeared to use backward reasoning strategies regardless of their level of
      expertise. This is a characteristic of non-expert decision-making. Experienced
      and less experienced nurses collected similar additional information before
      planning nursing interventions, supporting the conjecture that they were
      functioning at a non-expert level in relation to decision-making. No differences
      were seen in the information collected by graduate and non-graduate nurses.
      CONCLUSIONS: The decision-making strategies of children's nurses need exploring
      further and further research is needed to identify factors that may affect
      decision-making strategies. Several strategies to support nurses' clinical
      decision-making have been proposed but need testing to ascertain their
      effectiveness. RELEVANCE TO CLINICAL PRACTICE: In clinical practice nurses make
      numerous decisions throughout the course of a shift. Sub-optimal decision-making
      strategies may adversely affect the quality of nursing care provided. It is
      imperative, therefore, to ascertain how nurses make clinical decisions and the
      factors that may influence the decision-making strategies used.

PMID- 16968438
TI  - Living with a diabetic foot ulcer: a phenomenological study.

PMID- 16968439
TI  - Nurses and head nurses views of nursing diagnoses at a geriatric clinic.

PMID- 16968440
TI  - Commentary on Dunnion ME & Kelly B (2005). From the emergency department to home.
      Journal of Clinical Nursing 14, 776-785.

PMID- 16968441
TI  - Commentary on Hsieh P-L, Cholowski K & FitzGerald M (2005). Obesity: translation
      and testing of a survey instrument for use in Taiwan. Journal of Clinical Nursing
      14, 830-844.

PMID- 16968442
TI  - Commentary on Khorshid L, Eser I, Zaybak A and Yapucu U (2005). Comparing mercury
      in-glass, tympanic and disposable thermometers in measuring body temperature in
      healthy young people. Journal of Clinical Nursing 14, 496-500.

PMID- 16968443
TI  - Healthcare research without ethical permission should not be published in JCN.

PMID- 16968448
TI  - A java applet for exploring the new higher level classification of eukaryotes
      with emphasis on the taxonomy of protists.
AB  - We have converted the hierarchically organized new higher level classification of
      eukaryotes with emphasis on the taxonomy of protists proposed by Adl et al. into
      an interactive and dynamic Java applet. The current version of the applet can be
      accessed via http://phylogenetics.bioapps.biozentrum.uni-wuerzburg.de/etv. We use
      the layout from a Degree-of-Interest tree (DOITree) that effectively displays all
      the taxonomic information as well as the phylogenetic relationships described in
      the original article by Adl et al. The tree was made using the Prefuse Toolkit
      for interactive information visualization. All browsers capable of using Java
      applets will be able to view the tree. The applet is freely available for
      scientists, teachers, and students.

PMID- 16968449
TI  - In vitro propagation of two Perkinsus spp. parasites from Japanese Manila clams
      Venerupis philippinarum and description of Perkinsus honshuensis n. sp.
AB  - Perkinsus species are destructive parasites of commercial Manila clams, Venerupis
      philippinarum, in Japan, Korea, and Spain. However, in vitro parasite cultures
      from this important host clam are not available. Tissues of Manila clams
      collected during April 2002 in Gokasho Bay, Japan harbored Perkinsus sp.
      parasites at a 97% prevalence (28/29) of moderate- and high-intensity infections.
      Perkinsus sp. cells in tissue samples were enlarged in alternative Ray's fluid
      thioglycollate medium, before propagation in DME:Ham's F-12 Perkinsus sp. culture
      medium. Enlarged parasite hypnospores zoosporulated at high frequencies to
      release motile zoospores, which gave rise to continuous schizogonic cell lines
      that also zoosporulated continuously at low frequencies. Four Perkinsus sp. in
      vitro isolates comprising two distinct morphotypes were cryopreserved, cloned,
      and archived for public distribution. For three isolates of one morphotype,
      nucleotide sequences of the ribosomal DNA internal transcribed spacer region, of
      the large subunit rRNA gene, and of actin genes, were consistent with those
      reported for P. olseni. Similar sequences from one morphologically unique isolate
      differed from those of all described Perkinsus species. These results show that
      at least two Perkinsus spp. infect Japanese Manila clams, and that one represents
      a new species, Perkinsus honshuensis n. sp.

PMID- 16968450
TI  - Dinoflagellate, Euglenid, or Cercomonad? The ultrastructure and molecular
      phylogenetic position of Protaspis grandis n. sp.
AB  - Protaspis is an enigmatic genus of marine phagotrophic biflagellates that have
      been tentatively classified with several different groups of eukaryotes,
      including dinoflagellates, euglenids, and cercomonads. This uncertainty led us to
      investigate the phylogenetic position of Protaspis grandis n. sp. with
      ultrastructural and small subunit (SSU) rDNA sequence data. Our results
      demonstrated that the cells were dorsoventrally flattened, shaped like elongated
      ovals with parallel lateral sides, 32.5-55.0 mum long and 20.0-35.0 mum wide.
      Moreover, two heterodynamic flagella emerged through funnels that were positioned
      subapically, each within a depression and separated by a distinctive protrusion.
      A complex multilayered wall surrounded the cell. Like dinoflagellates and
      euglenids, the nucleus contained permanently condensed chromosomes and a large
      nucleolus throughout the cell cycle. Pseudopodia containing numerous mitochondria
      with tubular cristae emerged from a ventral furrow through a longitudinal slit
      that was positioned posterior to the protrusion and flagellar apparatus.
      Batteries of extrusomes were present within the cytoplasm and had ejection sites
      through pores in the cell wall. The SSU rDNA phylogeny demonstrated a very close
      relationship between the benthic P. grandis n. sp. and the planktonic
      Cryothecomonas longipes. These ultrastructural and molecular phylogenetic data
      for Protaspis indicated that the current taxonomy of Protaspis and Crythecomonas
      is in need of re-evaluation. The composition and identity of Protaspis is
      reviewed and suggestions for future taxonomic changes are presented. Problems
      within the genus Cryothecomonas are highlighted as well, and the missing data
      needed to resolve ambiguities between the two genera are clarified.

PMID- 16968452
TI  - Taxonomic characterization of Vorticella fuscaPrecht, 1935 and Vorticella
      parapulchella n. sp., two marine peritrichs (Ciliophora, Oligohymenophorea) from
      China.
AB  - Two marine peritrich ciliates, Vorticella fuscaPrecht (1935) and Vorticella
      parapulchella n. sp. were discovered in the littoral zone of Qingdao, northern
      China. Their morphology, infraciliature, and silverline system were described
      using live observation and silver impregnation. The poorly known species V. fusca
      is redescribed, adding information about the oral infraciliature and pellicular
      morphology. Vorticella parapulchella n. sp. is superficially similar to
      Vorticella pulchellaSommer (1951) but is distinguished from it by being markedly
      smaller and having much more widely spaced pellicular ridges. The infundibular
      infraciliature of V. parapulchella is extremely unusual in having infundibular
      polykinety 3 reduced to two rows, one of which has almost disappeared.

PMID- 16968451
TI  - A PCR-based method to distinguish the sibling species Stylonychia mytilus and
      Stylonychia lemnae (Ciliophora, Spirotrichea) using isocitrate dehydrogenase gene
      sequences.
AB  - A differentiation, based on morphological characters, between Stylonychia mytilus
      and Stylonychia lemnae is very difficult, especially for non-specialists. These
      two sibling species were considered as one species, S. mytilus, until detailed
      cytological and genetic studies could show the existence of two genetically
      isolated varieties. Further morphological and biochemical analyses verified the
      separation and finally in 1983 a new species S. lemnae was described. The
      examination of several isoenzymes revealed unambiguous differences in the banding
      pattern of isocitrate dehydrogenase (IDH) between these two species. Therefore,
      the IDH gene of 30 isolates of S. lemnae and S. mytilus coming from various
      regions all over the world were amplified and sequenced. The sequence analyses
      revealed intraspecific as well as interspecific substitutions, which were used
      for the development of species-specific PCR primers for both species. Application
      of these species-specific primer pairs now allows a very easy and clear
      identification of both sibling species.

PMID- 16968453
TI  - Population genetic structure of Carchesium polypinum (Ciliophora: Peritrichia) in
      four Chinese lakes inferred from ISSR fingerprinting: high diversity but low
      differentiation.
AB  - Although the peritrichous ciliate Carchesium polypinum is common in freshwater,
      its population genetic structure is largely unknown. We used inter-simple
      sequence repeat (ISSR) fingerprinting to analyze the genetic structure of 48
      different isolates of the species from four lakes in Wuhan, central China. Using
      eight polymorphic primers, 81 discernible DNA fragments were detected, among
      which 76 (93.83%) were polymorphic, indicating high genetic diversity at the
      isolate level. Further, Nei's gene diversity (h) and Shannon's Information index
      (I) between the different isolates both revealed a remarkable genetic diversity,
      higher than previously indicated by their morphology. At the same time,
      substantial gene flow was found. So the main factors responsible for the high
      level of diversity within populations are probably due to conjugation (sexual
      reproduction) and wide distribution of swarmers. Analysis of molecular variance
      (AMOVA) showed that there was low genetic differentiation among the four
      populations probably due to common ancestry and flooding events. The cluster
      analysis and principal component analysis (PCA) suggested that genotypes isolated
      from the same lake displayed a higher genetic similarity than those from
      different lakes. Both analyses separated C. polypinum isolates into subgroups
      according to the geographical locations. However, there is only a weak positive
      correlation between the genetic distance and geographical distance, suggesting a
      minor effect of geographical distance on the distribution of genetic diversity
      between populations of C. polypinum at the local level. In conclusion, our
      studies clearly demonstrated that a single morphospecies may harbor high levels
      of genetic diversity, and that the degree of resolution offered by morphology as
      a marker for measuring distribution patterns of genetically distinct entities is
      too low.

PMID- 16968454
TI  - Phylogeography of the cosmopolitan marine parasite Kudoa thyrsites (Myxozoa:
      Myxosporea).
AB  - Kudoa thyrsites (Myxozoa: Multivalvulida) is a cosmopolitan marine parasite of
      fishes associated with post-mortem tissue degradation. Financial losses incurred
      as a result of these infections are of concern to commercial fisheries. There is
      conflicting evidence whether K. thyrsites represents a cryptic species complex.
      Myxospore morphology is very similar for K. thyrsites across its range, but
      preliminary genetic analyses show some differences. Kudoa thyrsites and the
      morphologically similar Kudoa histolytica were examined from hosts in British
      Columbia, Canada, Oregon, USA, Chile, England, South Africa, Australia, and
      Japan. We compared myxospore morphology and DNA sequences of heat shock protein
      70 and the small subunit, large subunit, and internal transcribed spacer 1 of the
      ribosomal DNA. There was some morphological variation between regional
      representatives, inconsistent with genetic analyses. Phylogenetically, major
      separations correlated to four broad geographic regions: Japan, Australia,
      eastern Pacific, and eastern Atlantic. Within these regions there was little
      additional genetic structure. These data are evidence for regional subdivision of
      K. thyrsites suggesting global transplantation of fishes has yet to homogenize
      these distinctions. Within regions, parasite gene flow appears to be high between
      host species, suggesting little host specificity and minimal cryptic speciation.
      Our data also indicate that K. histolytica is not a valid species, as it was
      morphologically and genetically indistinguishable from K. thyrsites.

PMID- 16968455
TI  - Characterization of Kudoa monodactyli n. sp. (Myxosporea: Multivalvulida) from
      the Muscle of Monodactylus argenteus (Teleostei: Monodactylidae) from Moreton
      Bay, Queensland, Australia.
AB  - Kudoa monodactyli n. sp. is described from the somatic musculature of
      Monodactylus argenteus from several localities in southern Queensland, Australia.
      This is the first record of a myxozoan parasite from the family Monodactylidae.
      The spores typically have five polar capsules, making this species similar to the
      four other five-valved Kudoa species (K. neurophila, K. muscularis, K. shulmani,
      K. cutanea) that have been described to date. However, morphometric measurements
      particularly of spore length and width make the species from M. argenteus
      distinct from the other species. Comparison of the small subunit ribosomal DNA
      sequence of this species with its congeners for which sequence data are
      available, provides further evidence of novelty. Kudoa monodactyli n. sp.
      displays 38 (of 1,554) nucleotide differences compared with rDNA sequence of
      Kudoa neurophila, which on phylogenetic analysis places these species in clades
      exclusive of each other. Phylogenetic analyses also provide evidence that the
      number of valves per spore in this genus is an imperfect indicator of
      relatedness.

PMID- 16968456
TI  - Insights into the evolutionary origin and genome architecture of the unicellular
      opisthokonts Capsaspora owczarzaki and Sphaeroforma arctica.
AB  - Molecular phylogenetic analyses have recently shown that the unicellular amoeboid
      protist Capsaspora owczarzaki is unlikely to be a nucleariid or an ichthyosporean
      as previously described, but is more closely related to Metazoa,
      Choanoflagellata, and Ichthyosporea. However, the specific phylogenetic
      relationship of Capsaspora to other protist opisthokont lineages was poorly
      resolved. To test these earlier results we have expanded both the taxonomic
      sampling and the number of genes from opisthokont unicellular lineages. We have
      sequenced the protein-coding genes elongation factor 1-alpha (EF1-alpha) and heat
      shock protein 70 (Hsp70) from C. owczarzaki and the ichthyosporean Sphaeroforma
      arctica. Our maximum likelihood (ML) and Bayesian analyses of a concatenated
      alignment of EF1-alpha, Hsp70, and actin protein sequences with a better sampling
      of opisthokont-related protist lineages indicate that C. owczarzaki is not
      clearly allied with any of the unicellular opisthokonts, but represents an
      independent unicellular lineage closely related to animals and choanoflagellates.
      Moreover, we have found that the ichthyosporean S. arctica possesses an EF-like
      (EFL) gene copy instead of the canonical EF1-alpha, the first so far described in
      an ichthyosporean. A maximum likelihood phylogenetic analysis shows that the EF
      like gene of S. arctica strongly groups with the EF-like genes from
      choanoflagellates. Finally, to begin characterizing the Capsaspora genome, we
      have performed pulsed-field gel electrophoresis (PFGE) analyses, which indicate
      that its genome has at least 12 chromosomes with a total genome size in the range
      of 22-25 Mb.

PMID- 16968457
TI  - Species of tetrahymena identical by small subunit rRNA gene sequences are
      discriminated by mitochondrial cytochrome c oxidase I gene sequences.
AB  - The mitochondrial cytochrome c oxidase 1 (CO1) genes of two isolates of each of
      the seven mating types of Tetrahymena thermophila were sequenced and found to
      differ by < 1% in nucleotide sequence and to be identical by putative protein
      sequence. As this gene was highly conserved in this species, the CO1 gene
      sequence was determined for four pairs of Tetrahymena species identical in their
      small subunit rRNA gene sequences. The following pairs of species showed from 1%
      to 12% divergence at the nucleotide level, enabling discrimination of all these
      species: (1) Tetrahymena pyriformis strain T and Tetrahymena setosa strain HZ-1;
      (2) Tetrahymena canadensis strain UM1215 and Tetrahymena rostrata strain ID-3;
      (3) Tetrahymena pigmentosa strain UM1285 and Tetrahymena hyperangularis strain
      EN112; and (4) Tetrahymena tropicalis strain TC-105 and Tetrahymena mobilis.
      However, because of the synonymous nature of the majority of substitutions, the
      pairs of species were identical based on the putative protein sequence.

PMID- 16968458
TI  - Morphogenesis of the marine ciliate, Pseudoamphisiella alveolata (Kahl, 1932)
      Song & Warren, 2000 (Ciliophora, Stichotrichia, Urostylida) during binary
      fission.
AB  - Morphogenesis during the binary fission of the stichotrich ciliate
      Pseudoamphisiella alveolata, isolated from Jiaozhou Bay near Qingdao, China, was
      investigated using protargol silver impregnation. The process is characterized as
      follows: (1) in the proter, only the posterior part of the parental adoral zone
      of membranelles is renewed, where the membranelles dedifferentiate and then
      rebuild the UM-anlage and the missing membranelles, (2) the oral primordium in
      the opisthe and the FVT-anlagen in both dividers are formed de novo on the cell
      surface, (3) an "extra" anlage, which is generated on the right of the right
      marginal anlage, develops into three or four "extra" marginal cirri that connect
      the caudal cirri with the marginal rows, (4) the right marginal anlage is formed
      within the old structure, (5) the FVT-cirri develop in a primary mode, and (6)
      unlike most stichotrichs, the right marginal anlagen in both dividers generate
      closely together. As an additional contribution, the diversity of morphogenetic
      patterns within the genus Pseudoamphisiella is discussed. Based on both
      morphogenetic and SS rRNA gene sequencing data, the systematic position of the
      genus Pseudoamphisiella as well as the family Pseudoamphisiellidae Song et al.
      1997 is briefly analyzed. The results indicate that they should very possibly
      represent a higher evolved group in the order Urostylida.

PMID- 16968459
TI  - Reevaluation of the phylogenetic relationship between mobilid and sessilid
      peritrichs (Ciliophora, Oligohymenophorea) based on small subunit rRNA genes
      sequences.
AB  - Based on morphological characters, peritrich ciliates (Class Olygohymenophorea,
      Subclass Peritrichia) have been subdivided into the Orders Sessilida and
      Mobilida. Molecular phylogenetic studies on peritrichs have been restricted to
      members of the Order Sessilida. In order to shed more light into the evolutionary
      relationships within peritrichs, the complete small subunit rRNA (SSU rRNA)
      sequences of four mobilid species, Trichodina nobilis, Trichodina heterodentata,
      Trichodina reticulata, and Trichodinella myakkae were used to construct
      phylogenetic trees using maximum parsimony, neighbor joining, and Bayesian
      analyses. Whatever phylogenetic method used, the peritrichs did not constitute a
      monophyletic group: mobilid and sessilid species did not cluster together.
      Similarity in morphology but difference in molecular data led us to suggest that
      the oral structures of peritrichs are the result of evolutionary convergence. In
      addition, Trichodina reticulata, a Trichodina species with granules in the center
      of the adhesive disc, branched separately from its congeners, Trichodina nobilis
      and Trichodina heterodentata, trichodinids without such granules. This indicates
      that granules in the adhesive disc might be a phylogenetic character of high
      importance within the Family Trichodinidae.

PMID- 16968461
TI  - Immunomodulation by fluoroquinolones and other antibacterial agents.

PMID- 16968462
TI  - Forearm vasoconstrictor response in uncomplicated type 1 diabetes mellitus.
AB  - BACKGROUND: According to the 'haemodynamic hypothesis', increased tissue
      perfusion predisposes to microangiopathy in diabetic patients. We hypothesized
      that the typical haemodynamic changes underlying the increased tissue perfusion
      can be explained by a decreased sympathetic nerve activity caused by chronic
      hyperglycaemia. In this study we investigated sympathetic activity in patients
      with uncomplicated type 1 diabetes mellitus (DM). MATERIALS AND METHODS: In 15 DM
      patients (DM duration 6.3 +/- 3.8 year; HbA1c 7.9 +/- 1.3%) and 16 age- and sex
      matched healthy volunteers (Control), sympathetic nervous system activity was
      measured at rest (baseline) and during sympathoneural stimulation (lower body
      negative pressure (LBNP)) by means of interstitial and plasma noradrenaline (NA)
      sampling and power spectral analysis. Muscle sympathetic nerve activity (MSNA)
      was measured before (baseline) and during a cold pressure test. Forearm blood
      flow was measured during forearm vascular alpha- and beta-adrenergic receptor
      blockade. RESULTS: At baseline, forearm vascular resistance (FVR), plasma NA
      concentrations, MSNA and heart rate variability were similar in both groups. LBNP
      induced vasoconstriction was significantly attenuated in the DM group compared
      with the Control group (DeltaFVR: 12 +/- 4 vs. 19 +/- 3 arbitrary units, P <
      0.05). The responses of plasma NA and heart rate variability did not differ.
      CONCLUSIONS: Baseline FVR and sympathetic nerve activity are normal in patients
      with uncomplicated type 1 diabetes. However, the forearm vasoconstrictor response
      to sympathetic stimulation is attenuated, which cannot be attributed to an
      impaired sympathetic responsiveness.

PMID- 16968463
TI  - HFE mutations and risk of coronary heart disease in middle-aged women.
AB  - BACKGROUND: Although heterozygosity for the C282Y mutation in the HFE gene has
      been associated with an increased risk of cardiovascular events, epidemiological
      studies remain inconclusive. The aim of the present study was to obtain further
      evidence as to whether HFE mutations are associated with risk of coronary heart
      disease (CHD) in middle-aged women. We used data of a cohort of 15 236 Dutch
      middle-aged women to investigate whether C282Y carriers and H63D carriers are at
      increased risk of coronary heart disease compared with non-carriers. MATERIALS
      AND METHODS: Women were included in the study between 1993 and 1997 and were
      followed until 1 January 2000 for cardiovascular events. HFE genotyping was
      performed on all 211 coronary heart disease cases and a randomly selected sample
      from the baseline cohort (n = 1526). A weighted Cox proportional hazards model
      was used to estimate crude, age-adjusted and multivariate adjusted hazard ratios
      for C282Y and H63D carriership in relation to coronary heart disease. RESULTS:
      Compared with non-carriers, those that carried the C282Y allele were not at
      increased risk for CHD (HR = 1.25, 95% CI = 0.74-2.09). Neither did we find an
      association between the H63D mutation and CHD risk (HR = 0.73, 95% CI = 0.43
      1.24). CONCLUSIONS: Our results are in accordance with similar studies to date,
      for which we present a meta-analysis. HFE mutations appear not to affect the risk
      of coronary heart disease.

PMID- 16968464
TI  - Inflammatory and endothelial markers in women with polycystic ovary syndrome.
AB  - BACKGROUND: Women with polycystic ovary syndrome (PCOS) carry a pattern of
      cardiovascular risk factors. Endothelial dysfunction and chronic inflammation are
      early findings in the atherosclerotic process. The purpose of the study was to
      investigate the coexistence of active inflammation markers and endothelial
      dysfunction in young women with PCOS, and their relationship with metabolic and
      hormonal abnormalities of the syndrome. MATERIALS AND METHODS: Twenty-five young
      women with PCOS and 25 controls of similar age and body mass index (BMI) were
      studied. Endothelial function was assessed by flow-mediated dilatation (FMD) on
      the brachial artery and smooth muscle cells injury was excluded by nitrate
      induced dilatation (NID). Plasma levels of endothelin-1 (ET-1), soluble
      intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion
      molecule-1 (sVCAM-1) and high sensitivity C-reactive protein (hsCRP) were
      measured. Hormonal and metabolic profiles were determined in both groups.
      RESULTS: Flow-mediated dilatation (FMD) was statistically lower in PCOS (P <
      0.001), whereas nitrate-induced dilatation (NID) was similar within the two
      groups. Polycystic ovary syndrome (PCOS) had statistically higher levels of ET-1
      (P = 0.03), sICAM-1 (P = 0.01), sVCAM-1 (P = 0.02) and hsCRP (P = 0.01).
      Furthermore FMD was statistically higher in PCOS population with hsCRP 1 mg L(-1)
      when compared with PCOS population with hsCRP > 1 mg L(-1) (P = 0.02). Flow
      mediated dilatation (FMD) was negatively related to hsCRP (r = -0.512, P =
      0.015); ET-1 was positively related to free androgen index (r = 0.27, P = 0.05)
      and negatively to sex hormone-binding globulin (r = -0.465, P = 0.022); sVCAM-1
      was positively related to total testosterone (r = 0.431, P = 0.036); hsCRP was
      positively related to BMI (r = 0.647, P = 0.001), and negatively related to FMD
      (r = -0.512, P = 0.015), quantitative insulin sensitivity check index (QUICKI) (r
      = -0.499, P = 0.018), and MATSUDA index (r = -0.445, P = 0.038). CONCLUSIONS: The
      present study demonstrates that endothelial dysfunction coexists and is
      influenced by the presence of increased serum levels of inflammation and
      endothelial activation markers in young women with PCOS. These parameters appear
      to be interrelated with hyperandrogenaemia in this insulin-resistant population.

PMID- 16968465
TI  - Homocysteine, traditional risk factors and impaired renal function in coronary
      artery disease.
AB  - BACKGROUND: To establish whether the frequent finding of a moderate-intermediate
      increase in plasma total homocysteine (tHcy) causes coronary artery disease
      (CAD), the authors evaluated the number of coexisting major traditional risk
      factors, as well as the major tHcy determinants, in patients with the same degree
      of CAD but different tHcy levels. MATERIALS AND METHODS: The authors studied 180
      patients with CAD, who were divided into three groups according to tHcy levels:
      60 patients with normal tHcy, 60 patients with moderate (15-30 micromol L(-1))
      and 60 patients with intermediate hyperhomocysteinaemia (30-100 micromol L(-1)).
      The patient groups were matched for gender, age and number of affected coronary
      vessels. All patients were checked for the presence of traditional risk factors
      for CAD (i.e. hypertension, diabetes, hyperlipidaemia, smoking habit, familial
      history, obesity), as well as determinants of tHcy levels. The population was
      subdivided into those having, or not, a substantial burden of traditional risk
      factors (i.e. < 4 and > or = 4, respectively). RESULTS: There was a significant
      trend towards a reduced number of subjects within the group with > or = 4 risk
      factors across increasing tHcy levels (51.7%, 37.8%, 26%, for normal, moderate,
      intermediate tHcy, respectively, chi2 for linear-trend = 0.006). Folate and
      vitamin B12 concentrations, estimated glomerular filtration rate (GFR), MTHFR
      677C > T polymorphism were the major determinants of tHcy in this population.
      CONCLUSIONS: In patients with the same degree of CAD, those with
      hyperhomocysteinaemia had a reduced burden of traditional risk factors as
      compared with those with normal tHcy levels. Hyperhomocysteinaemia was
      significantly associated with an emerging non-traditional risk factor such as
      lower GFR.

PMID- 16968466
TI  - Increased cardiac endothelial nitric oxide synthase expression in patients taking
      angiotensin-converting enzyme inhibitor therapy.
AB  - BACKGROUND: The efficacy of angiotensin-converting enzyme (ACE) inhibitors has
      been demonstrated in large clinical trials, but knowledge of the underlying
      mechanisms remains incomplete. Therefore, this study investigated the impact of
      ACE inhibitor therapy on cardiac nitric oxide (NO) synthases in patients with
      coronary artery disease (CAD) or heart failure. PATIENTS AND METHODS: The mRNA
      expression was quantified by standard calibrated competitive RT-PCR, protein
      expression by Western blotting and NOS activity by monitoring the conversion of
      [3H]arginine to [3H]citrulline during enzymatic formation of NO in tissue
      homogenates of myocardium of patients with, or without, ACE inhibitor treatment
      before elective coronary artery bypass grafting or heart transplantation.
      RESULTS: The mRNA expression (amol microg(-1) RNA) of endothelial NO synthase
      (eNOS) was higher (22.5 +/- 4.8, n = 23) in the atrial myocardium of patients
      taking ACE inhibitor treatment, before elective coronary artery bypass grafting,
      compared with patients not taking this therapy (8.9 +/- 0.7, n = 33, P < 0.0001).
      The ACE inhibitor therapy increased eNOS protein expression from [(9 +/- 0.7)
      relative units (RUs) to (12 +/- 0.9) RUs, P < 0.05, respectively] and cardiac NOS
      activity from 17.6 +/- 1.3 to 23.7 +/- 1.1 pmol mg protein(-1) min(-1) (P <
      0.001, respectively). Inducible and neuronal NO synthase expression was not
      changed by the ACE inhibition. A similar up-regulation of eNOS by ACE inhibition
      was found in the left ventricles of patients with heart failure. The augmented
      endothelial NOS expression and activity was not the result of differences in
      clinical characteristics and concomitant therapy between the patient groups.
      CONCLUSION: Increased eNOS expression and activity might contribute to the
      beneficial effects of ACE inhibitor therapy in the treatment of CAD and heart
      failure.

PMID- 16968467
TI  - Myostatin expression in ventricular myocardium in a rat model of volume-overload
      heart failure.
AB  - BACKGROUND: Mechanical stress increases myocardial myostatin expression. However,
      the expression of myostatin in chronic heart failure resulting from volume
      overload and after treatment with beta-blockers is little known. The authors
      hypothesize that myostatin plays a role in the failing myocardium because of
      volume-overload. MATERIALS AND METHODS: Aorto-caval shunt was created over a 4
      week period in adult Sprague-Dawley rats to induce volume-overload heart failure.
      RESULTS: Heart weight and body weight ratio significantly increased after
      shunting. The left ventricular end-diastolic dimension also significantly
      increased. Treatment with carvedilol in the shunt group reversed the increase in
      heart weight and ventricular dimension to the baseline values. Myocardial and
      skeletal myostatin proteins were up-regulated in the shunt group. The mRNA of
      myocardial myostatin also increased in the shunt group. Treatment with carvedilol
      reversed both protein and mRNA of myocardial myostatin to the baseline values.
      Treatment with N-acetylcysteine and doxazosin partially decreased myostatin mRNA
      and protein expression as compared with the shunt group. Carvedilol normalized
      the increased immunohistochemical labelling of myocardial myostatin in the shunt
      group. CONCLUSION: Myocardial myostatin mRNA and protein expression were up
      regulated in the rat model of volume-overload heart failure. Treatment with
      carvedilol is associated with a limitation of increased myostatin expression in
      the failing ventricular myocardium.

PMID- 16968468
TI  - Ciprofloxacin inhibits cytokine-induced nitric oxide production in human colonic
      epithelium.
AB  - BACKGROUND: The fluoroquinolone ciprofloxacin is a broad-spectrum antibiotic that
      has been used in the treatment of inflammatory bowel diseases. There is evidence
      that quinolones have immunomodulating activities via the regulation of cytokine
      production. MATERIALS AND METHODS: We investigated the effect of ciprofloxacin on
      the nitric oxide (NO) production by colonic epithelium. HT-29 cells and colonic
      biopsies from patients (n = 4) with ulcerative colitis (UC) and normal controls
      (n = 4) were cultured with various concentrations of ciprofloxacin (10-100 microg
      mL(-1)) in the presence and absence of pro-inflammatory cytokines. The production
      of NO was measured in culture supernatants with a spectrophotometric method and
      inducible nitric oxide synthase (iNOS) mRNA expression was examined by reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: Ciprofloxacin did not
      have any effect on the basal NO production by HT-29 cells. In contrast,
      ciprofloxacin significantly (P < 0.001) inhibited the pro-inflammatory cytokines
      (interleukin-1alpha + tumour necrosis factor-alpha + interferon-gamma)-induced NO
      production in HT-29, in a concentration-dependent manner, via the inhibition of
      the cytokine-induced iNOS mRNA expression. Wortmannin produced a concentration
      related reversal of the inhibitory effect of ciprofloxacin at both iNOS mRNA
      expression and NO production in HT-29 cells. A similar inhibitory effect of
      ciprofloxacin on the cytokine-induced NO production and iNOS mRNA expression was
      detected in vitro in cultures of normal colonic tissue. In addition,
      ciprofloxacin significantly inhibited the NO production and iNOS mRNA expression
      in cultures of colonic tissue from ulcerative colitis patients, in a
      concentration-dependent manner. CONCLUSIONS: These data suggest that
      ciprofloxacin, in addition to its antimicrobial role, might have an
      immunoregulatory effect on intestinal inflammation, via the modulation of
      inflammatory mediators.

PMID- 16968469
TI  - Combined LDI/SAT test to evaluate intestinal lactose digestion and mucosa
      permeability.
AB  - BACKGROUND: Intestinal mucosal damage causes impaired digestive capacity and
      increased mucosal permeability. Quantification of damage can be used to improve
      treatment options. Currently, the Lactose Digestion Index (LDI) and the Sugar
      Absorption Test (SAT) are used for evaluation. The investigation studied whether
      both tests could be combined to provide a useful multifunctional test and whether
      measurements in blood (LDI) could be replaced by measurements in urine. MATERIALS
      AND METHODS: The LDI (25 g 13C-lactose, 0.5 g 2H-glucose), the SAT (5 g
      lactulose, 1 g L-rhamnose) and the LDI/SAT combination test were performed in
      seven lactose-digesting and eight lactose-maldigesting adults. Plasma glucose 13C
      enrichment was determined by gas-chromatography/combustion/isotope ratio mass
      spectrometry (GC/C/IRMS), 2H enrichment determined by gas-chromatography/mass
      spectrometry (GC/MS) and urinary sugars by gas-chromatography (GC). RESULTS: The
      results of the separate LDI test were not different from those of the LDI/SAT in
      the lactose-digester group (0.82 +/- 0.06 vs. 0.81 +/- 0.09), nor in the lactose
      maldigester group (0.36 +/- 0.12 vs. 0.35 +/- 0.06). A significant correlation
      was found between the 10-h urinary-lactose/lactulose ratio and the LDI (R2 =
      0.71, P < 0.01). There were no differences in the lactulose/L-rhamnose ratio
      between lactose-digesters and lactose-maldigesters using both the SAT and LDI/SAT
      tests. CONCLUSION: The LDI/SAT test is a reliable method of measuring digestion
      and permeability simultaneously. The 10-h period urinary lactose/lactulose
      excretion ratio following lactose consumption reflects lactose digestive
      capacity.

PMID- 16968470
TI  - Effect of lactose on oro-cecal transit in lactose digesters and maldigesters.
AB  - BACKGROUND: The transit time of the small intestine, in addition to lactase
      activity, may influence lactose digestion and thus play a role in the occurrence
      of lactose intolerance. The objectives of this study were to investigate the
      effect of lactose on the oro-cecal transit time (OCTT) in lactose digesters and
      maldigesters as well as the possible mechanisms underlying these effects.
      MATERIALS AND METHODS: Twenty-eight Chinese subjects and 16 Dutch subjects
      underwent one glucose and one lactose challenge in two single-blinded tests.
      Twenty of the Chinese subjects without complaints after the challenge then
      underwent another lactose challenge. A 6-h symptom score (SSC) was recorded,
      breath-hydrogen concentration was measured and OCTT after consumption of glucose
      and lactose was determined with the lactose-[13C] ureide breath test. The lactose
      digestion index (LDI) was determined in both the Dutch and 20 Chinese subjects
      with the 13C/2H-glucose test. RESULTS: Lactose digesters (n = 13) and
      maldigesters (n = 20) were classified based on the results of the LDI and the
      breath-hydrogen test. The OCTT after the lactose and glucose challenges did not
      differ in the digesters, whereas in the maldigesters the OCTT, after the lactose
      challenge, was shorter than that after glucose. There was no difference in OCTT
      after the glucose challenge between the maldigesters and the digesters. However,
      the OCTT after the lactose challenge in the maldigesters was shorter than that in
      the digesters. The LDI of the digesters was significantly higher than that of the
      maldigesters. The OCTT after the lactose challenge was not correlated to the LDI
      in the maldigesters nor in the digesters. Based on the SSC after the one glucose
      and two lactose challenges, a tolerant (n = 7) and an intolerant (n = 5) group
      were classified in the Chinese subjects. The two groups did not differ in their
      LDI or OCTT after the lactose challenge. The OCTT after the lactose challenge was
      not correlated to the SSC or the LDI. CONCLUSIONS: Lactose triggers a faster oro
      cecal transit in lactose maldigesters, but not in digesters. However, this could
      not be explained by intestinal distension resulting from the osmotic load posed
      by maldigested lactose, and thus suggests a direct effect of lactose on intrinsic
      factors regulating intestinal motility.

PMID- 16968471
TI  - Iron enhances endothelial cell activation in response to Cytomegalovirus or
      Chlamydia pneumoniae infection.
AB  - BACKGROUND: Chronic inflammation has been implemented in the pathogenesis of
      inflammatory diseases like atherosclerosis. Several pathogens like Chlamydia
      pneumoniae (Cp) and cytomegalovirus (CMV) result in inflammation and thereby are
      potentially artherogenic. Those infections could trigger endothelial activation,
      the starting point of the atherogenic inflammatory cascade. Considering the role
      of iron in a wide range of infection processes, the presence of iron may
      complicate infection-mediated endothelial activation. MATERIALS AND METHODS:
      Endothelial intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion
      molecule-1 (VCAM-1) and endothelial selectin (E-selectin) expression were
      measured using flow cytometry, as an indication of endothelial activation.
      Cytotoxicity was monitored using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. Immunostaining was applied to measure Cp
      and CMV infectivity to endothelial cells. RESULTS: An increased number of
      infected endothelial cells in a monolayer population leads to a raised expression
      of adhesion molecules of the whole cell population, suggesting paracrine
      interactions. Iron additively up-regulated Cp-induced VCAM-1 expression, whereas
      synergistically potentiated Cp-induced ICAM-1 expression. Together with CMV, iron
      also enhanced ICAM-1 and VCAM-1 expression. These iron effects were observed
      without modulation of the initial infectivity of both microorganisms. Moreover,
      the effects of iron could be reversed by intracellular iron chelation or radical
      scavenging, conforming modulating effects of iron on endothelial activation after
      infections. CONCLUSIONS: Endothelial response towards chronic infections depends
      on intracellular iron levels. Iron status in populations positive for Cp or CMV
      infections should be considered as a potential determinant for the development of
      atherosclerosis.

PMID- 16968472
TI  - Blockade of noradrenaline transport abolishes 4-methylthioamphetamine-induced
      contraction of the rat aorta in vitro.
AB  - The aim of this study was to characterize the effects of 4-methylthioamphetamine
      (4-MTA) on contractility and noradrenaline (NA) transport and release in the
      isolated rat aorta. Descending thoracic aortic rings were isolated from male
      Wistar rats (220-240 g) and the effect of 4-MTA on contractility was measured by
      isometric force displacement. 4-MTA (0.1 microm-1 mm) induced a concentration
      dependent contraction of aortic rings, with a pD(2) of 4.40 +/- 0.38, and an
      E(max) of 0.80 +/- 0.05 g tension. The alpha(1)-adrenoceptor antagonist, prazosin
      (1 microm) and alpha(2) antagonist, yohimbine (1 microm) inhibited maximal
      contraction to 100 microm 4-MTA by 45.0 +/- 6.7% and 53.5 +/- 7.1% of control
      values respectively, whereas the 5-hydroxytryptamine (5-HT) antagonist,
      ketanserin (100 nm) had no effect on the 4-MTA-mediated contraction. The specific
      NA transport inhibitor, nisoxetine (1 microm) abolished contraction of the aorta
      by 4-MTA. 4 Nisoxetine-sensitive [(3)H]-NA transport in aortic rings was measured
      over a concentration range of 0-5 microm [(3)H]-NA, and had a maximal rate of
      transport (V(max)) of 0.77 +/- 0.07 pmol [(3)H]-NA min(-1) mg(-1) protein and a
      Michaelis affinity constant (K(M)) of 2.3 +/- 0.5 microm. 4-MTA inhibited
      nisoxetine-sensitive [(3)H]-NA transport with a pIC(50) of 6.16 +/- 0.18 and the
      pIC(50) for inhibition of nisoxetine-sensitive [(3)H]-NA transport by 3,4
      methylenedioxymethamphetamine (MDMA) was 6.83 +/- 0.13. 4-MTA (1-100 microm)
      significantly stimulated release of pre-loaded [(3)H]-NA from aortic rings and 4
      MTA-induced [(3)H]-NA release was inhibited by 1 microm nisoxetine. These data
      suggest that 4-MTA causes contraction of the rat aorta in vitro by a mechanism
      that is consistent with an ability to cause release of NA at the level of the NA
      transporter. It is concluded that 4-MTA has the potential to increase the
      extracellular concentration of NA peripherally as well as centrally, and that
      this may cause adverse cardiovascular effects in its users.

PMID- 16968473
TI  - Alpha(1A/L)-adrenoceptors mediate contraction of the circular smooth muscle of
      the pig urethra.
AB  - Sympathetically mediated urethral tone is essential for the maintenance of
      continence and involves the activation of postjunctional alpha(1)-adrenoceptors.
      This study characterizes the alpha(1)-adrenoceptor subtypes responsible for
      mediating contraction of the urethral circular smooth muscle of the pig. The
      potency order of a number of agonists and the affinities of several receptor
      selective antagonists were determined on pig-isolated circular smooth muscle
      strips in the presence of cocaine (1 microm) and corticosterone (10 microm) to
      inhibit amine uptake and propranolol (1 microm) to antagonize beta-adrenoceptors.
      The potency order for agonists was N-[5-(4,5-dihydro-1H-imidazol-2yl)-2-hydroxy
      5,6,7,8-tetrahydronaphthalen-1-yl]methanesulphonamide (A61603) > noradrenaline =
      phenylephrine = M6434 > methoxamine with pEC(50) values of 7.3, 5.8, 5.7, 5.6 and
      5.0 respectively. 4 The alpha(1D)-adrenoceptor-selective antagonist 8-[2-[4-(2
      methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4,5]decane-7,9-dione (BMY7378)
      caused rightward shifts of the concentration-response curves to noradrenaline,
      yielding a low affinity estimate (6.6) for the urethral receptor. The alpha(1A)
      adrenoceptor-selective antagonists, RS100329 and 5-methylurapidil, gave
      relatively high affinity estimates (9.6 and 8.8 respectively) for this receptor.
      All three antagonists produced Schild plots with slopes close to unity but did
      reduce maximum responses at higher concentrations. Prazosin antagonized responses
      of the urethra to noradrenaline, yielding a mean affinity estimate of 9.0.
      Although the Schild plot for prazosin again had a slope of unity, this drug also
      reduced maximum responses to noradrenaline at all concentrations examined (10-100
      nm). N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha,alpha-dimethyl-1H
      indole-3-ethanamide (RS17053), which discriminates between responses mediated via
      alpha(1A) (high affinity) and alpha(1L)-adrenoceptors (low affinity) at
      concentrations up to 3 microm, failed to antagonize responses of the urethra. 5
      These results suggest that contraction of urethral circular smooth muscle in the
      pig is mediated via a single population of adrenoceptors with the pharmacological
      characteristics of the alpha(1A/L)-adrenoceptor, most probably the alpha(1L)
      adrenoceptor.

PMID- 16968474
TI  - Long-term streptozotocin-induced diabetes alters prostanoid production in rat
      aorta and mesenteric bed.
AB  - Vascular disease is a major cause of mortality and morbidity in chronic diabetes
      mellitus. Prostanoids, metabolites of arachidonic acid, include vasoactive
      substances produced and released from the vascular wall. Alterations in
      prostanoid production have been reported in the vasculature of diabetic humans
      and experimental animals. The aim of the present work was to study the influence
      of three different periods of long-term streptozotocin-induced diabetes, 30, 120
      and 180 days in the production of prostanoids in the thoracic aorta and in the
      mesenteric vascular bed of the rat. The prostanoids released to the incubation
      medium by the tissues were extracted and measured by reversed-phase HPLC. In the
      diabetic groups, body weight was reduced and glycaemia was increased when
      compared with the corresponding non-diabetic controls. In the aorta, 30 days of
      diabetes did not modify the prostanoid release pattern, meanwhile 120 and 180
      days of incubation decreased prostacyclin (PGI(2)) production. In the mesenteric
      bed, at 30 days the release of the vasodilators PGI(2) and prostaglandin (PGE(2))
      and the vasoconstrictor thromboxane (TXA(2)) was reduced. At 120 days the
      vasodilators were reduced and at 180 days such reduction was joined by an
      increase of the release of vasoconstrictor metabolites. Thirty days of diabetes
      did not modify the PGI(2)/TXA(2) ratio in the aorta or mesenteric bed. On the
      other hand, 120 and 180 days of diabetes reduced significantly the ratio when
      compared with the corresponding controls. In conclusion, the mesenteric bed, a
      resistance vascular bed, seems to be more sensitive than the aorta, a conductance
      vessel, to the effects of diabetes on prostanoid production. The observed effects
      contribute to a displacement of the balance of prostanoid release in favour of
      the vasoconstrictor metabolites, a phenomenon that could be related to the
      vascular complications of diabetes mellitus.

PMID- 16968475
TI  - Dopamine receptor subtypes in the human pulmonary arterial tree.
AB  - Dopamine induces vasorelaxation of pulmonary artery primarily through an
      endothelium-dependent mechanism, but dopamine receptor subtypes involved in these
      mechanisms have not been identified yet. The expression and localization of
      dopamine D1-like (D1 and D5) and D2-like (D2, D3 and D4) receptors were
      investigated in hilar, lobar and intrapulmonary branches of human pulmonary
      artery by immunoblotting and immunohistochemistry. Pulmonary artery expresses
      dopamine D1, D2, D4 and D5 receptor subtypes, but not the D3 receptor subtype.
      Dopamine D1 and to a lesser extent D5 receptors were accumulated primarily in the
      endothelium of extrapulmonary branches of pulmonary artery. A faint dopamine D1
      and D5 receptor immunoreactivity was found in the inner media of extrapulmonary
      and of large sized intrapulmonary branches of pulmonary artery, but not in medium
      or small-sized intrapulmonary artery branches. Dopamine D2 and to a lesser
      extent D4 receptor immunoreactivity co-localized with the tyrosine hydroxylase
      immunoreactive sympathetic plexus supplying pulmonary artery was found in the
      adventitia and in the adventitia-media of both extra- and different-sized
      intrapulmonary branches of pulmonary artery. These findings suggest the possible
      role of dopamine receptors in the pulmonary endothelium-dependent vasorelaxing
      activity. The D1 receptor subtype seems to be the most involved in this
      mechanism. Dopamine D2-like receptors are prejunctional and are located at the
      level of sympathetic neuroeffector plexus. The heterogeneous distribution and
      density of dopamine receptor subtypes along the human pulmonary arterial tree may
      be related to the different functional roles of dopamine at various levels of the
      pulmonary circulation.

PMID- 16968476
TI  - Selective agonists reveal alpha(1A)- and alpha(1B)-adrenoceptor subtypes in
      caudal artery of the young rat.
AB  - Multiple alpha(1)-adrenoceptors were evaluated in caudal artery of the young
      Wistar rat using selective agonists and antagonists. Arteries were exposed to the
      selective alpha(1A)-adrenoceptor agonist, A-61603 (N-[5-(4,5-dihydro-1H-imidazol
      2-yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl] methanesulfonamide) or to
      phenylephrine and to prazosin (alpha(1)-adrenoceptor antagonist), or the
      selective alpha(1A)-adrenoceptor antagonists 5-methylurapidil, RS 100329 (5
      methyl-3-[3-[4-[2-(2,2,2,-trifluoroethoxy)phenyl]-1-piperazinyl]propyl]-2,4-(1H)
      pyrimidinedione), RS 17053 (N-[2(2-cyclopropylmethoxy) ethyl]-5-chloro-alpha,
      alpha-dimethyl-1H-indole-3-ethanamide), and the selective alpha(1D)-adrenoceptor
      antagonist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8
      azaspiro[4.5] decane-7,9-dione). Results showed a 100-fold higher potency of A
      61603 for the alpha(1)-adrenoceptor present in the artery, compared with
      phenylephrine. Prazosin displaced both agonists with high affinity, whereas 5
      methylurapidil, RS 100329 and RS 17053 displaced A-61603 with high affinity,
      indicating the presence of alpha(1A)-adrenoceptors. The selective alpha(1A)
      adrenoceptor antagonists blocked phenylephrine responses with low affinity,
      suggesting that phenylephrine activated a second receptor population in caudal
      artery. BMY 7378 antagonized with low affinity both A-61603 and phenylephrine
      induced contractions, indicating absence of alpha(1D)-adrenoceptors in the
      vessel. The results suggest that functional alpha(1B)-adrenoceptors are present
      in caudal arteries of the young Wistar rat.

PMID- 16968477
TI  - Abstracts of the 3rd International Conference on Living Donor Abdominal Organ
      Transplantation, June 23-24, 2006, Sardegna, Italy.

PMID- 16968478
TI  - Excellent clinical outcomes in primary kidney transplant recipients treated with
      steroid-free maintenance immunosuppression.
AB  - Steroid-free maintenance immunosuppression is desirable to eliminate the side
      effects of chronic corticosteroid use. Complete steroid avoidance or rapid post
      transplant steroid withdrawal has recently been used in renal transplant
      recipients with encouraging results. The present study evaluated the outcome of a
      steroid-free maintenance immunosuppressive protocol in kidney transplant
      recipients with at least one-yr follow up. Between April 2002 and October 2004, a
      total of 301 primary kidney transplant recipients received steroid-free
      maintenance immunosuppression. The regimen consisted of induction with
      thymogobulin and prednisone for the first five d. Patients were maintained on
      Sirolimus and Neoral. Neoral dose was adjusted to target C2 levels and the
      Sirolimus dose was adjusted to a target rapamycin trough level. All primary
      kidney transplants (n = 502) performed in the two yr (starting January 2000)
      prior to institution of the steroid-free regimen and thus maintained on a steroid
      based immunosuppressive protocol were used for comparison. One-year patient and
      death censored graft survival were 93.1% and 98.1% for the steroid-free group vs.
      95.2% and 95.2% for the comparator groups (p = ns). The incidence of biopsy
      proven acute rejection was 4.9% in the steroid-free group vs. 9.4% in the
      comparator group (p < 0.01). Two (0.7%) of 301 patients in the steroid-free group
      lost their grafts because of acute rejection compared with nine (1.8%) patients
      in the comparator group (p < 0.05). At one-yr post-transplant the mean serum
      creatinine level was not different between the two groups. There were no
      significant differences in mean serum cholesterol and triglycerides levels as
      well as the percentage of patients on lipid lowering agents between the groups.
      White blood cell counts, daily doses of Neoral and weight gain were significantly
      lower in the steroid-free group vs. the comparator group. However, more patients
      in the steroid-free group required erythropoietin and iron therapy for anemia (p
      < 0.001). We conclude that excellent graft survival with a significantly lower
      incidence of acute rejection can be achieved using a steroid-free maintenance
      immunosuppressive protocol consisting of Neoral and Sirolimus.

PMID- 16968479
TI  - The transmission of donor-derived malignant melanoma to a renal allograft
      recipient.
AB  - The transmission to organ transplant recipients of donor origin malignancy in the
      allograft has been described. Here we report the transmission of malignant
      melanoma in a renal allograft transplanted from a multiorgan donor. The lung
      transplant recipient presented with an allograft lesion that was proven to be
      melanoma and of donor-origin based on human leukocyte antigen (HLA)-DR typing.
      One renal allograft recipient was undergoing his second deceased donor renal
      transplant, having lost his first graft from recurrent IgA nephropathy. He was
      unsensitized and immunosuppression consisted of tacrolimus, mycophenolate and
      prednisolone. He achieved stable graft function and there were no episodes of
      rejection. Four and a half months post-transplant a diagnosis of donor origin
      melanoma in the lung recipient was made and his immunosuppression was stopped. He
      presented with clinical rejection two wk later and a transplant nephrectomy was
      undertaken. Histology demonstrated vascular and cellular rejection and there was
      a 3-mm melanoma deposit with no evidence of tumour infiltrating lymphocytes.
      Three years post-transplant he remained clinically well with no evidence of
      melanoma and received his third deceased donor renal transplant. This was
      complicated by cellular rejection in the first week treated with
      methylprednisolone and vascular rejection at day 10 treated with anti-thymocyte
      globulin. Three months post-transplant he has achieved good allograft function
      and remains well with no evidence clinically or on imaging of metastatic
      melanoma. The other renal allograft recipient was receiving his first deceased
      donor transplant, having end-stage renal failure of uncertain aetiology. His
      immunosuppression was not stopped until melanoma was proven in the renal
      allograft pair six months post-transplant and he then presented with clinical
      rejection six wk later. Transplant nephrectomy was undertaken and histology did
      not demonstrate melanoma, but severe vascular and cellular rejection was evident.
      At three-yr post-transplant he remains disease free clinically and on imaging. At
      present, the cardiac allograft recipient has no evidence of transmitted melanoma.
      The highest risk of transmission of donor origin melanoma appears to be from
      donors who are older and have died from an intracerebral haemorrhage. It is
      likely these donors have metastatic melanoma and their intracerebral haemorrhage
      is not primary but has occurred in an unrecognized metastatic cerebral deposit.
      While the occurrence of donor-transmitted malignancy is not common, the outcome
      is often fatal.

PMID- 16968480
TI  - Surgical strategies for liver transplantation in the case of portal vein
      thrombosis--current role of cavoportal hemitransposition and renoportal
      anastomosis.
AB  - Portal vein thrombosis (PVT), a common complication of end stage liver disease,
      is no longer considered a definite contraindication for liver transplantation
      (LTx). The clinical decision to perform an LTx in the case of PVT depends on the
      degree of PVT and the experience of the surgeon. Eversion thromboendovenectomy
      was suggested by most authors as the surgical technique of choice for PVT grade
      1, 2, and 3. If PVT obstructs more extended parts of the porto-mesenteric venous
      circulation, surgical options would include different types of venous jump graft
      reconstructions or arterialization of the portal vein. Combined liver and small
      bowel transplantation is another possible alternative. Cavoportal
      hemitransposition (CPHT) and renoportal anastomosis (RPA) were recently
      particularly advocated as creative surgical strategies in case of diffuse PVT. In
      this work, we focus on CPHT and RPA surgical techniques during LTx, which
      attempts to secure the portal flow to the liver graft in case of pre-existent
      diffuse PVT. We provide a review of all reported clinical experience at
      international clinical centers using these techniques. According to our meta
      analysis a total of 15 studies were published on this topic between 1996 and
      2005. In summary, a total of 56 orthotopic LTx have been performed in 53 patients
      (28 men, 25 women) combined with either CPHT or RPA, for the purpose of providing
      the donor graft with adequate inflow. Mean age was 44 yr including two patients
      who were infants, with the youngest recipient being two yr old. Main indications
      for LTx were liver cirrhosis caused by viral hepatitis, alcoholic cirrhosis and
      cryptogenic cirrhosis. CPHT was performed in 46 cases, and RPA in 10 cases.
      Thirty-five of 53 patients (66%) had surgery previous to LTx. Of these, 13
      patients (37%) [corrected] presented with a history of other previous surgical
      procedures for decompression of portal hypertension or treatment of associated
      complications (portocaval shunts, splenectomy, etc). Ascites, renal dysfunction,
      lower extremity and torso edema and variceal bleeding were dominant post
      operative complications after CPHT or RPA noted in 22 cases (41.5%), 18 cases
      (34%), 17 cases (32%) and 13 cases (24.5%) respectively. Patients' follow-up
      ranged from two to 48 months. Thirty nine of 53 patients [corrected] (74%)
      survived [corrected] and 14 patients died (26%) [corrected] during the course of
      observation. Based on the literature, we conclude that the ideal technique to
      overcome PVT during LTx is still controversial. Short-term follow-up results of
      both methods are promising, however, long-term results are unknown at present.
      Furthermore, clinical follow-up and basic experimental work is required to
      evaluate the influence of systemic venous inflow to the liver graft with respect
      to long-term liver function and liver regeneration.

PMID- 16968481
TI  - Successful renal transplantation despite low levels of donor-specific HLA class I
      antibody without IVIg or plasmapheresis.
AB  - We prospectively transplanted 10 primary kidney recipients with deceased donor
      organs (nine kidney and one pancreas/kidney) when their flow cytometric T-cell
      IgG, HLA class I donor-specific crossmatch was positive but the AHG T-cell
      crossmatch was negative, with a median follow-up of 1.8 yr. No pre- or peri
      operative IVIg or plasmapheresis was administered to any patient. All but one of
      the 11 organs transplanted into patients with a flow T(+)/AHG(-) crossmatch is
      currently functioning despite the continued presence of circulating low levels of
      HLA class I antibody. Flow HLA class I antigen-coated beads showed the presence
      of at least one donor-specific HLA class I antibody at transplantation in each of
      the 10 cases. No rejections were observed in seven of the 10 cases (70%). Six
      rejection episodes, four cellular and two humoral, occurred in three patients.
      Each rejection was successfully treated. The only graft loss occurred in a kidney
      recipient on day 667 secondary to ischemia to the kidney because of cardiac
      surgery. Thus, short-term (one to two years) graft survival in primary
      transplants was not influenced by low levels of donor-specific HLA class I
      antibody present at transplantation and no prophylactic treatment such as IVIg,
      plasmapheresis, anti-CD20 or splenectomy was needed peri-operatively.

PMID- 16968482
TI  - Steroid-free immunosuppression regime reduces both long-term cardiovascular
      morbidity and patient mortality in renal transplant recipients.
AB  - The aim of this retrospective study was to assess the impact of steroid therapy
      on cardiovascular disease (CVD) and patient mortality, in 486 on-CsA renal
      transplant recipients, with a follow-up of 9.5 +/- 4.3 yr. Two hundred and one
      patients had their steroids permanently withdrawn at sixth month after
      transplantation (G1); 285 patients did not (G2) as they were unable (acute
      rejection after suspension) or unsuitable (because of clinical criteria or
      immunosuppressive protocols). The CVD considered were coronary artery disease
      diagnosed by angiography and myocardial infarction. G1 and G2 patients were well
      matched regarding CVD risk factors, except for age (G1: 44 +/- 14 yr; G2: 40 +/-
      12 yr; p < 0.003), incidence of male (G1: 62%; G2: 72%, p < 0.02) incidence of
      acute rejection (G1: 39%; G2: 83%, p < 0.0001). Both CVD and deaths occurring
      during the first year of transplantation were excluded from the analysis. At 20
      yr, the cumulative probability of developing a CVD, was 3.8% in G1; 23.8% in G2
      (p < 0.0005). Patient survival rate was 95% in G1; 62% in G2 (p < 0.003).
      Mortality caused by CVD was higher in G2 (4.2% vs. 0.5%; p < 0.03). The Cox
      analysis identified in steroid therapy the main independent risk factors for both
      CVD (hazard ratio 9.56 p < 0.0001) and patient mortality (hazard ratio 5.99, p <
      0.0001). At 10th and 15th year after transplantation, the mean-daily dose of
      steroids was 4.2 mg. In the long-term, steroid therapy, even in low-doses,
      increases significantly both the rate of CVD and patient mortality. This
      retrospective study suggests that steroid-free regime should always be
      recommended for the prevention of post-transplant CVD. This relevant statement
      should be followed by a long-term prospective study.

PMID- 16968483
TI  - Body mass index as a predictive factor for long-term renal transplant outcomes in
      Asians.
AB  - BACKGROUND: There is substantial evidence that renal transplant recipients with
      obesity or body mass index >30 kg/m(2) have increased risk of graft loss.
      However, few data exist for Asian population; clinicians have to rely upon
      indirect evidence by extrapolating the results from Caucasians to Asian
      recipients. STUDY: Using data from a study population of 150 consecutive
      cadaveric or living related Chinese renal transplant recipients at our center
      between 1985 and 2002, we examined the effect of baseline body mass index cut-off
      25 kg/m(2) on the transplant outcomes using Kaplan-Meier analysis and Cox
      proportional hazards analysis. Primary study end point was overall graft
      survival. RESULTS: The mean body mass index was 22.9 +/- 4.0 kg/m(2). Thirty
      seven (25%) patients were classified as overweight and 113 patients as non
      overweight, using the cut-off of 25 kg/m(2). After median follow up period of
      nine yr, 15 graft losses (41%) occurred in the overweight group, as compared with
      14 graft losses (12%) in the non-overweight group. Kaplan-Meier estimates of
      cumulative graft survival at five yr were significantly worse for the overweight
      group than non-overweight group (83.6% versus 92.7%, p = 0.0041). By multivariate
      Cox proportional hazards analysis, baseline body mass index > or =25 kg/m(2)
      conferred a significantly higher risk of graft loss (with relative risk of 4.78,
      95% CI = 1.52-15.2) and doubling of serum creatinine (relative risk 3.19, 95% CI
      = 1.22-8.40). Death with a functioning graft occurred in 11% of overweight
      recipients, compared with 3% among the non-overweight group (p = 0.041).
      CONCLUSION: Our results draw attention to a recipient body mass index cut-off
      value > or =25 kg/m(2), which might confer an increased risk of graft loss in
      Asian kidney transplant populations.

PMID- 16968484
TI  - Revival of effective and safe high-dose mizoribine for the kidney
      transplantation.
AB  - We investigated whether high-dose Mizoribine (MIZ: a water-soluble anti
      metabolite), 4-6 mg/kg/d was as effective and safe as mycophenolate mofetil (MMF)
      for patients after kidney transplantation. Between January 2001 and December
      2005, 36 recipients at a stable phase more than one month passed after
      transplantation underwent conversion from MMF to MIZ, two from Azathioprine to
      MIZ, and two cases on MIZ from the beginning. There were 24-male and 16-female
      patients whose average age was 43.3 yr old and average weight was 54.0 kg. The
      types of transplantations were living donor renal transplantation 25, cadaveric
      renal transplantation 11, and simultaneous pancreas-kidney transplantation four
      examples. Of these, 33 patients were on Tacrolimus-based triple regimen and seven
      patients on Cyclosporine A base. The drugs used together with MIZ were basically
      the same as those before conversion. The reasons for conversion to MIZ were
      infection in 18 cases (45.0%), bone marrow suppression in nine cases (22.5%) and
      diarrhea in eight cases (20.0%), and post-transplant lymphoproliferative disorder
      in one case (2.5%). We initiated 4-6 mg/kg/d of MIZ divided twice a day depending
      on the serum creatinine (sCr) value of each patient. There was no big difference
      in the sCr value before and after MIZ administration in each individual patient,
      1.79 +/- 1.37 and 1.65 +/- 1.30 mg/dL, respectively. A 12 h pharmaco-kinetic
      study of MIZ revealed that a peak value reached 2.87 microg/mL on average at
      three h (C3) followed by a slow decrease afterward. Acute rejection occurred in
      two cases and adverse effects were seen in five cases. The results of analysis of
      349 points divided into three groups by renal function were as follows; poor
      renal function Group A revealed a trough level of 2.21 +/- 0.99 microg/mL and
      dosage 2.20 +/- 1.06 mg/kg, good renal function Group B had a trough level of
      1.06 +/- 0.82 microg/mL and dosage 4.40 +/- 1.72 mg/kg, and excellent function
      Group C had a trough level of 0.92 +/- 0.55 microg/mL and dosage of 4.36 +/- 1.08
      mg/kg. High-dose MIZ 4-6 mg/kg/d is an anti-metabolite having an equivalent
      immunosuppressive effect, fewer serious adverse events and good cost
      effectiveness as MMF even for patients with prolonged hemodialysis period and
      declined digestive function in Japan.

PMID- 16968485
TI  - Creatinine-based formulae for the estimation of glomerular filtration rate in
      heart transplant recipients.
AB  - Chronic renal failure (CRF) is a common complication in heart transplant
      patients. Serum creatinine has clear limitations for the detection and estimation
      of glomerular filtration rate (GFR). Various creatinine-based formulae are
      classically used for GFR estimation, but little scientific evidence exists for
      such use in a heart transplant population. GFR was measured using the plasmatic
      clearance of the glomerular tracer (51)Cr-EDTA in 27 heart transplant patients
      with two measures for 22 of the patients. Forty-nine measures were thus available
      for analysis. The precision and accuracy (Bland and Altman analysis) of the
      Cockcroft, simplified Modified Diet in Renal Diseases (MDRD) and new Mayo Clinic
      formulae were compared. The mean GFR of the population was 39 +/- 15 mL/min/1.73
      m(2). All formulae were well correlated with the GFR. With the Bland and Altman
      analysis, the accuracy of the MDRD formula appeared higher than that of the
      Cockcroft or the Mayo Clinic formulae (bias of +12 mL/min/1.73 m(2), vs. +19.9
      mL/min/1.73 m(2), and +22.1 mL/min/1.73 m(2), respectively). The difference
      between the estimated and measured GFR was higher than 20 mL/min/1.73 m(2) in 51%
      and 55% cases when using the Cockcroft and the Mayo Clinic formulae respectively,
      whereas the difference was only noted in 14% cases when the MDRD was used. Among
      creatinine-based formulae, the MDRD appears the most precise and accurate for
      estimating the GFR in heart transplant patients. However, when the GFR must be
      measured with high accuracy, we recommend the use of a reference method like
      inulin or (51)Cr-EDTA plasma clearance techniques.

PMID- 16968486
TI  - Successful reuse of liver grafts after death of the first recipient.
AB  - Brain death secondary to cerebrovascular disease is a possible early complication
      of orthotopic liver transplantation. If liver graft continues to function
      normally, the reuse of liver for another patient may be considered. We report
      three cases of successful reuse of liver grafts after death of the first
      recipient. In our experience, liver graft can be reused in the first weeks after
      a previous transplantation provided that liver function is good, in the absence
      of systemic uncontrolled infection, graft rejection and after gross graft
      examination at laparotomy.

PMID- 16968487
TI  - End-to-side caval anastomosis in adult piggyback liver transplantation.
AB  - No consensus exists regarding the optimal reconstruction of the cavo-caval
      anastomosis in piggyback orthotopic liver transplantation (PB-LT). The aim of
      this study was to analyze our experience with end-to-side (ES) cavo-cavostomy.
      Outcome parameters were patient and graft survival and surgical complications.
      During the period 1995-2002 146 full-size PB-LT in 137 adult patients were
      performed with ES cavo-cavostomy without the routine use of temporary portocaval
      shunt (TPCS). In 12 patients (8%) this technique was used for implantation of
      second or third grafts. Veno-venous bypass was not used in any case and TPCS was
      performed only in eight patients (6%). One-, three- and five-yr patient and graft
      survival were 84%, 79% and 75%, and 81%, 74% and 69%, respectively. The median
      number of intraoperative transfusion of packed red blood cells (RBC) was 2.0
      (range 0-33) and 30% of the patients (n = 43) did not require any RBC
      transfusion. Surgical complications of various types were observed after 49 LT
      (34%) and none of the complications was specifically related to the technique of
      ES cavo-cavostomy. Our experience indicates that PB-LT with ES cavo-cavostomy is
      a safe procedure, can safely be performed without the routine use of a TPCS, has
      a very low risk of venous outflow obstruction and can also be used effectively
      during retransplantations.

PMID- 16968488
TI  - De novo malignancies following liver transplantation: a case-control study with
      long-term follow-up.
AB  - BACKGROUND: Long-term survival data on de novo malignancy are limited following
      orthotopic liver transplantation (OLT) when compared with controls without
      malignancies. METHODS: Over a 12 yr period at our institution, 50 of 1043
      patients (4.8%) who underwent OLT were identified to have 53 de novo
      malignancies. The clinical characteristics and survival of these patients were
      retrospectively reviewed and compared with a control cohort of 50 OLT recipients
      without malignancy matched with the incidence cases by age, year of OLT, sex, and
      type of liver disease. RESULTS: Chronic hepatitis C, alcohol and primary
      sclerosing cholangitis were the three leading causes of liver disease. Skin
      cancer was the most common malignancy (32%), followed by gastrointestinal (21%),
      including five small bowel tumors, and hematologic malignancies (17%). The cases
      and controls were not significantly different in the immunosuppressive regimen (p
      = 0.42) or the number of rejection episodes (p = 0.92). The five- and 10-year
      Kaplan-Meier survival rates for the cases were 77% and 34%, respectively, vs. 84%
      and 70%, respectively, for the controls (p = 0.02 by log-rank test). Patients
      with skin cancers had survival similar to the controls, but significantly better
      than non-skin cancers (p = 0.0001). The prognosis for patients with
      gastrointestinal tumors was poor, with a median survival of 8.5 months after the
      diagnosis. CONCLUSION: In this single institutional study, de novo malignancies
      after OLT were uncommon. Patients with non-skin cancer after OLT had diminished
      long-term survival compared with the controls. Our results differ from other
      reports in the high incidence of gastrointestinal malignancies with attendant
      poor prognosis.

PMID- 16968489
TI  - Characterization of CD4, CD8, CD56 positive lymphocytes and C4d deposits to
      distinguish acute cellular rejection from recurrent hepatitis C in post-liver
      transplant biopsies.
AB  - INTRODUCTION: Hepatitis C viral (HCV) infection is the most common cause for
      liver transplantation (LTx) in USA. Hepatitis C viral recurrence in liver
      allograft is almost universal, which is often difficult to distinguish from acute
      cellular rejection (ACR). AIM: Aim of the present study is to examine the
      differences between distribution of CD4, CD8, CD56 positive lymphocytes, and C4d
      deposits in patients with ACR and recurrent HCV. PATIENTS AND METHODS: As a pilot
      project, a group of five post-LTx HCV RNA negative patients, strongly suspicious
      for ACR based on clinical findings and history of medication non-compliance and
      another group of five post-LTx HCV positive, medication compliant patients with
      abnormal liver function were retrospectively selected. Liver biopsies of these
      patients were stained with monoclonal CD4, CD8, CD56, and polyclonal C4d
      antibodies and compared. RESULTS: Mean CD4, CD8, and CD56 counts in ACR group
      were 156.7 +/- 17.6, 35.4 +/- 8.8, and 1.0 +/- 1.8/HPF, respectively and were
      89.7 +/- 41.3, 20.3 +/- 23.2, and 0.6 +/- 0.9/HPF, respectively in HCV recurrence
      group. Biopsies of four of five patients with ACR demonstrated moderate to strong
      C4d staining, whereas all patients with recurrent HCV had none to mild C4d
      staining. CONCLUSION: Mean CD4, CD8, and CD56 were similar for acute rejection
      and recurrent HCV infection. However, 80% of patients with ACR showed moderate to
      strong staining for C4d and all recurrent HCV patients showed none to mild C4d
      staining.

PMID- 16968490
TI  - New onset diabetes mellitus post-kidney transplantation.
AB  - The study explores the prevalence of unrecognized diabetes mellitus (DM), the
      incidence and risk factors new onset diabetes mellitus (NODM) and determines
      whether patient survival differs between patients with transient (NODM that
      resolves) compared with those with fixed NODM. This is a single center review of
      solitary kidney recipients transplanted from 1993 to 2003. Of the 381 patients
      without DM pre-transplant, 111 met criteria for DM post. Of these 17 were
      unrecognized to have DM, 31 had transient (resolved) NODM and 64 had fixed NODM.
      In a multivariate analysis, age, body mass index, repeat transplant and rejection
      were risk factors for NODM. In a separate analysis of only fixed NODM, tacrolimus
      use showed a trend for an independent association (HR 1.7 95% CI 0.95-2.9). NODM
      patient survival was comparable to non-diabetic recipients even up to 10 yr;
      however, excess mortality started to be seen in the fixed NODM subgroup at late
      follow up. Use of more stringent DM criteria results in a population with
      relatively good intermediate term survival and allows detection and treatment of
      early disease. Transient NODM represents approximately one third of NODM and has
      a relatively good prognosis.

PMID- 16968491
TI  - Changes of clotting factors (7, 9 and 10) and hepatocyte growth factor in
      patients with thrombotic microangiopathy after bone marrow transplantation.
AB  - To investigate risk factors for thrombotic microangiopathy (TMA) after bone
      marrow transplantation (BMT), the levels of three clotting factors (7, 9 and 10)
      and hepatocyte growth factor (HGF) were measured. Among 46 consecutive patients
      who underwent BMT, six developed TMA and 40 did not. The levels of the clotting
      factors and HGF did not differ significantly between the six patients with TMA
      and the 40 patients without it. In two patients who developed TMA during the
      earlyperiod after BMT, however, the levels of the three clotting factors were
      significantly decreased even before BMT, along with a significant increase of
      HGF. These findings suggest that patients with severe hepatic dysfunction before
      BMT, especially those with impaired protein synthesis, had an increased risk of
      developing TMA soon after BMT. It was also suggested that measurement of clotting
      factors (7, 9 and 10) and HGF may be useful to predict the occurrence of TMA in
      the early period after BMT.

PMID- 16968492
TI  - Secondary syphilis after liver transplantation: case report and review of the
      literature.
AB  - Syphilitic disease is uncommon, but its incidence has increased worldwide in the
      last few years. An unusual manifestation of secondary syphilis after orthotopic
      liver transplantation is described which confirms that lues should be considered
      in patients with immune deficiency and abnormal liver function tests.

PMID- 16968493
TI  - Increased cardiovascular risk profile and mortality in kidney allograft
      recipients with post-transplant diabetes mellitus in Spain.
AB  - BACKGROUND: Post-transplant diabetes mellitus (PTDM) is associated with poorer
      outcomes in kidney transplantation (KT) but little information exists about the
      evolution of traditional cardiovascular risk (CVR) factors under this disorder.
      METHODS: We retrospectively analysed CVR factors at 3, 12 and 24 months of follow
      up and mortality at three yr in 3365 KT performed in Spain during the years 1990,
      1994 and 1998 with a functioning graft after the first year. Three groups were
      considered: (i) (PTDM, n, 251), (ii) diabetes mellitus as primary disease (DM, n
      = 156) and (iii) the remaining patients (controls, n = 2958). RESULTS: Recipient
      age, weight and body mass index (BMI) were higher in PTDM than in the other
      groups (p < 0.0001), with a lower increase of body weight during follow-up (p <
      0.003). PTDM patients showed higher total-cholesterol levels than controls at one
      (p < 0.01) and two yr (p < 0.0009), and higher triglyceride levels than the other
      groups during follow-up (p < 0.002). Compared with Controls, PTDM patients had
      significantly higher systolic blood pressure at one (p < 0.001) and two yr (p <
      0.005). Diastolic blood pressure was higher in PTDM and controls (p < 0.001),
      while pulse pressure was higher in PTDM and DM patients (p < 0.0001) during
      follow-up. Using Cox proportional hazards analysis, PTDM correlated with total
      mortality (RR = 1.55; range 1.05-2.3; p < 0.02) but not with cardiovascular
      mortality. CONCLUSIONS: In Spanish KT recipients with graft function after one
      yr, PTDM is associated with a worse traditional CVR profile and a higher overall
      mortality. Although short-term cardiovascular mortality remains similar, better
      control of CVR factors is mandatory to prevent long-term cardiovascular mortality
      inherent to this population.

PMID- 16968494
TI  - Relative risk of new-onset diabetes during the first year after renal
      transplantation in patients receiving tacrolimus or cyclosporine
      immunosuppression.
AB  - Clinical trials have consistently shown a higher incidence of new-onset diabetes
      mellitus with tacrolimus than cyclosporine. However, in protocol-driven studies
      steroid doses are comparable in both treatment arms, while in clinical practice
      steroid dose used in conjunction with tacrolimus or cyclosporine may differ. This
      retrospective study analysed renal transplant recipients without pre-existing
      diabetes receiving tacrolimus (n = 100) or cyclosporine (n = 100) for whom one
      year follow-up data were available. Diabetes was defined as use of insulin or
      oral hypoglycemic agents; fasting glucose >6.9 mmol/L; or non-fasting glucose >11
      mmol/L on three consecutive occasions. Tacrolimus-treated patients were
      significantly older than cyclosporine-treated patients (49 +/- 14 vs. 44 +/- 13
      yr, p < 0.05) and received a significantly lower cumulative dose of
      corticosteroids over the first three months post-transplant (1284 +/- 379 vs.
      1714 +/- 486 mg, p < 0.0001). At 3, 6, 9 and 12 months significantly more
      tacrolimus-treated patients had new-onset diabetes than cyclosporine- treated
      patients. At 12 months, 18 patients receiving tacrolimus and two receiving
      cyclosporine had diabetes (p < 0.0001). There was a clear relationship between
      age and incidence of new-onset diabetes at three months in the tacrolimus cohort.
      After stratifying patients by age group, the frequency of diabetes was
      significantly higher with tacrolimus than with cyclosporine in patients aged 40
      60 yr [8/46 (17.4%) vs. 2/48 (4.2%), p < 0.05] and >60 yr [9/28 (32.1%) vs. 0/14
      (0%), p < 0.05]. The mean tacrolimus trough level during the first three months
      was similar in patients with diabetes (13.1 +/- 2.3 ng/mL) or without diabetes
      (13.0 +/- 2.8 ng/mL, n.s.). These results indicate that new-onset diabetes is
      strongly and significantly associated with tacrolimus vs. cyclosporine in renal
      transplant recipients, even when steroid dosing is lower with tacrolimus.

PMID- 16968495
TI  - Re: Gender-associated risk factors for cardiac end points and total mortality
      after renal transplantation.

PMID- 16968497
TI  - Standardization of sample preparation, staining and sampling methods for
      automated sperm head morphometry analysis of boar spermatozoa.
AB  - The accuracy of computer-assisted sperm morphometry analysis (CASMA) depends on
      the careful preparation, fixation and staining of spermatozoa. The efficiency of
      CASMA may be enhanced by developing optimized protocols. The aim of the present
      study was to evaluate the influence of sperm washing and the use of three
      staining techniques [rapid Panoptic, Hemacolor and Harris's Haematoxylin (HH)] on
      image-processing accuracy and boar sperm head morphometry. Sperm washing had a
      significant effect on samples stained with rapid Panoptic, increasing the
      percentage of correctly binarized sperm heads and the contrast between cells and
      background. However, rapid Panoptic yielded the lowest percentage of properly
      digitized sperm heads. HH provided the highest cell/background contrast, and also
      greater sperm head staining intensity, but discrimination of sperm midpieces was
      considered insufficient. Hemacolor occupied an intermediate position, providing
      acceptable colour intensity and satisfactory cell/background contrast. Use of
      different staining procedures prompted dimensional differences in sperm head
      morphometry. Significant differences between animals were observed for all
      morphometric parameters. Low within-animal variation coefficients reflected a
      homogeneous sperm head population. Between-animal variation coefficients were
      relatively high for Hemacolor and HH, and significantly high for the rapid
      Panoptic stain. Using Panoptic and HH, stable morphometric measurements required
      at least 100 properly digitized sperm heads rather than 200, while Hemacolor
      required only 50 spermatozoa. These results indicate that both washing of semen
      and staining procedures significantly affect the accuracy of image processing and
      sperm head dimensions. Hemacolor and HH proved to be the best staining techniques
      for evaluating sperm head dimensions in boar.

PMID- 16968498
TI  - Direct nitric oxide measurement in human spermatozoa: flow cytometric analysis
      using the fluorescent probe, diaminofluorescein.
AB  - We have demonstrated that intracellular nitric oxide (NO) can be detected and
      measured directly in human spermatozoa by flow cytometry using the fluorescent
      probe 4,5-diaminofluorescein-2/diacetate (10 microM). This method can measure
      both exogenously added as well as endogenously generated intracellular NO.

PMID- 16968499
TI  - Culture and medical malpractice: lessons from Japan. Is the "reluctant plaintiff"
      a myth?

PMID- 16968500
TI  - Medical malpractice litigation in gastroenterological practice in Japan: a 22-yr
      review of civil court cases.

PMID- 16968501
TI  - Paracentesis.

PMID- 16968502
TI  - Double-blind, placebo-controlled trial with single-dose pantoprazole for
      laryngopharyngeal reflux.
AB  - OBJECTIVES: Results of randomized treatment trials for laryngopharyngeal reflux
      (LPR) are mixed. The cause and effect between gastroesophageal reflux and
      laryngeal symptoms remain elusive. AIMS: To determine the efficacy of single-dose
      pantoprazole in newly diagnosed LPR and to correlate hypopharyngeal reflux with
      symptom improvement. METHODS: Randomized, double-blind, placebo-controlled trial
      was performed with a 2-wk run-in, 12-wk treatment period (pantoprazole 40 mg
      q.a.m. or placebo), and 4-wk follow-up. Study criteria were laryngeal complaints
      >3 days/wk and a positive triple-sensor pH test. Laryngeal exam was graded using
      a reflux finding score before and after treatment. Repeat pH test was performed
      on study drug at week 12. Weekly diaries were kept on symptom severity and global
      assessment. Total laryngeal symptom score was defined as the sum of six laryngeal
      symptoms. Mann-Whitney U, Wilcoxon, and Pearson tests were used. RESULTS: Thirty
      nine subjects (13 M/26 F, median age 39 yr) were randomized; 35 completed the
      study. During the treatment period, total laryngeal symptom scores significantly
      improved compared with pretreatment scores in both study groups, but there were
      no significant differences between them. Forty percent of pantoprazole group
      reported adequate relief at week 12, compared with 42% of placebo group (p=
      0.89). No significant improvement in hypopharyngeal reflux was found in either
      study group. There were no significant correlations between laryngeal reflux
      finding scores and hypopharyngeal reflux episodes with symptom improvement.
      CONCLUSIONS: Response was similar between single-dose pantoprazole and placebo in
      newly diagnosed LPR. Our results suggested that laryngeal exam was not useful in
      following treatment response. Hypopharyngeal reflux may represent acid reflux or
      artifacts, but is not likely the underlying cause.

PMID- 16968503
TI  - Levofloxacin-based triple therapy in first-line treatment for Helicobacter pylori
      eradication.
AB  - BACKGROUND: The standard first-line therapies for Helicobacter pylori eradication
      are based on clarithromycin and amoxicillin or metronidazole. Recent studies
      suggested levofloxacin as an alternative option for both first-and second-line H.
      pylori eradication treatment. AIMS: To compare efficacy and tolerability of two
      different 7-day standard triple therapies versus 7-day levofloxacin-based triple
      therapy in first-line treatment for H. pylori infection. METHODS: Three hundred
      consecutive H. pylori positive patients were randomized to receive:
      clarithromycin, amoxicillin, esomeprazole (Group A: N = 100); clarithromycin,
      metronidazole, esomeprazole (Group B: N = 100); or clarithromycin, levofloxacin,
      esomeprazole (Group C: N = 100). H. pylori status was rechecked by (13)C urea
      breath test 6 wk after the end of therapy. RESULTS: Sixteen out of 300 patients
      discontinued treatment because of the occurrence of side effects (Group A, 5;
      Group B, 7; Group C, 4). The eradication rates in intention to treat (ITT) and
      per protocol (PP) analyses were: Group A, 75% and 79%; Group B, 72% and 77.4%;
      and Group C, 87% and 90.6%. The eradication rate achieved with levofloxacin-based
      triple therapy was significantly higher than that with standard therapies in
      either ITT (87%vs 75%, p <0.05; 87%vs 72%, p <0.01;) or PP analysis (90.6%vs 79%,
      p <0.05; 90.6 vs 77.4, p <0.05). No difference was found between standard triple
      therapies. The incidence of side effects was similar among groups. CONCLUSIONS: A
      7-day levofloxacin-based triple therapy can achieve higher H. pylori eradication
      rates than standard regimens. These data suggest levofloxacin-based regimens can
      be the most effective in first-line anti-H. pylori therapy, at least in the
      Italian population.

PMID- 16968504
TI  - Continuous infusion of pantoprazole versus ranitidine for prevention of ulcer
      rebleeding: a U.S. multicenter randomized, double-blind study.
AB  - OBJECTIVES: No North American randomized study has compared ulcer rebleeding
      rates after endoscopic hemostasis in high-risk patients treated with high-dose
      intravenous (IV) proton pump inhibitors (PPIs) or IV histamine-2 receptor
      antagonists. Our hypothesis was that ulcer rebleeding with IV pantoprazole (PAN)
      would be lower than with IV ranitidine (RAN). METHODS: This was a multicenter,
      randomized, double-blind, U.S. study. Patients with bleeding peptic ulcers and
      major stigmata of hemorrhage had endoscopic hemostasis with thermal probes with
      or without epinephrine injection, then were randomly assigned to IV PAN 80 mg
      plus 8 mg/h or IV RAN 50 mg plus 6.25 mg/h for 72 h, and subsequently had an oral
      PPI (1/day). Patients with signs of rebleeding had repeat endoscopy. Rebleeding
      rates up to 30 days were compared in an intention-to-treat analysis. RESULTS: The
      study was stopped early because of slow enrollment (total N = 149, PAN 72, RAN
      77). Demographics, APACHE II scores, ulcer type/location, stigmata, and
      hemostasis used were similar. The 7- and 30-day rebleeding rate was 6.9% (5 of 72
      patients) with PAN and 14.3% (11 of 77) for RAN (p= 0.19). Rebleeds occurred
      within 72 h in 56% and between 4 and 7 days in 44% of patients. The 30-day
      mortality rate was 4%. Nonbleeding severe adverse events were more common in the
      RAN than in the PAN group (14 [18.1%]vs 7 [9.7%], p= 0.16). CONCLUSIONS: Because
      of the small sample size of this study, there was an arithmetic but not
      significant difference in ulcer rebleeding rates.

PMID- 16968505
TI  - To establish the efficacy of PPI therapy for ulcer bleeding in the United States,
      do we need more patients or more PPI [corrected].
AB  - Proton pump inhibitor (PPI) therapy is widely used in the management of patients
      with ulcer bleeding. However, most randomized controlled trials (RCTs) have been
      conducted outside of the United States. Jensen and colleagues have conducted the
      first United States-based RCT to compare a PPI with an H(2)-receptor antagonist
      following appropriate endoscopic hemostatic treatment for patients with ulcer
      bleeding. Unfortunately, the trial had to be discontinued prematurely because of
      problems with enrolment. There was a statistically nonsignificant difference in
      rebleeding rates between the two treatment arms. A type II statistical error
      probably explains this apparent lack of efficacy. However, U.S. patients may also
      require higher doses of PPI for adequate control of intragastric acidity.

PMID- 16968506
TI  - Efficacy of bispectral monitoring as an adjunct to nurse-administered propofol
      sedation for colonoscopy: a randomized controlled trial.
AB  - BACKGROUND AND AIMS: Bispectral (BIS) monitoring provides an objective, non
      invasive measure of the level of consciousness in sedated patients. BIS has been
      shown to lag behind the level of sedation during induction and emergence of
      sedation with propofol. In this study, we sought to determine whether BIS is a
      useful adjunctive maneuver to registered nurse-administered propofol sedation
      (NAPS) as measured by reductions in recovery time and doses of propofol
      administered. METHODS: A randomized controlled trial of 102 outpatients
      presenting for colonoscopy was performed. BIS values were recorded continuously
      in all subjects. Patients were randomized to receive NAPS with BIS visible to
      nurse and endoscopist versus BIS invisible to nurse and endoscopist. In phase 1
      (47 patients), the nurse and endoscopist team were instructed to consider BIS
      (when visible) as only adjunctive information with regard to titrating sedation.
      In phase 2 (55 patients), the nurse endoscopist team was instructed to use BIS as
      the primary endpoint for titration of sedation, and to target BIS to greater than
      60 (60-70 is deep sedation). RESULTS: In phase 1, the mean (SD) BIS value from
      scope-in (SI) to scope-out (SO) for BIS was 59.3 (9.9) and was not different from
      controls at 59.9 (10.1; p= 0.82). The mean (SD) propofol dose (mg/min) was 15.8
      (5.6) and 17.2 (6.2) for BIS and controls, respectively (p= 0.45). The mean (SD)
      recovery time with BIS visible in phase 1 was 20.6 min (5.5) versus 19.2 min
      (4.5) in controls (p= 0.34). In phase 2, the mean (SD) BIS from SI to SO in those
      randomized to have BIS visible was 64.1 (5.4) versus 63.1 (8.5) in controls (p=
      0.58). The mean (SD) dose of propofol (mg/min) was 16.1 (11.2) and 16.4 (12.3)
      for BIS and control groups, respectively (p= 0.92). The mean (SD) recovery time
      in phase 2 with BIS visible was 18.7 (3.5) versus 20.1 (5.6) in controls (p=
      0.27). CONCLUSIONS: BIS did not lead to reductions in mean propofol dose or
      recovery time when used as an adjunct to NAPS for colonoscopy, or when used as
      the primary target for sedation. No clinically important role for BIS monitoring
      as an adjunct to NAPS has yet been established.

PMID- 16968507
TI  - Sedation for endoscopic procedures: not as simple as it seems.
AB  - The Bispectral Index (BIS) is a processed electroencephalogram, which has been
      evaluated as an automated monitoring technique for patients receiving sedation
      for endoscopic procedures. BIS monitoring has not been shown to be of significant
      clinical benefit, but the need for an objective quantitative measure of the depth
      of sedation in patients undergoing endoscopy remains.

PMID- 16968508
TI  - Prospective comparison of push enteroscopy and push-and-pull enteroscopy in
      patients with suspected small-bowel bleeding.
AB  - BACKGROUND AND AIMS: The management of patients with suspected mid
      gastrointestinal bleeding has in the past been difficult, as push enteroscopy
      (PE) only allows limited endoscopic access for diagnosis and treatment. Recently
      published uncontrolled data on push-and-pull enteroscopy (PPE) using the double
      balloon technique suggest that this new method has a high diagnostic yield and
      therapeutic efficacy. A prospective controlled study was therefore carried out to
      compare PPE with PE as the common nonsurgical gold standard method. METHODS: The
      diagnostic yield, complications, and various examination parameters were compared
      in 52 consecutive patients with suspected mid-gastrointestinal bleeding who were
      evaluated with both enteroscopy methods. RESULTS: No relevant complications were
      observed with either method. Sedoanalgesia, examination times, and X-ray exposure
      were lower with PE. The insertion depth was significantly greater with PPE than
      with PE (230 cm vs 80 cm, p < 0.0001). The overall diagnostic yield with PPE (38
      of 52 patients, 73%) and the results of oral PPE only (33 of 52 patients, 63%)
      were superior to those with PE (23 of 52 patients, 44%; p < 0.0001). PPE
      identified additional lesions in deeper parts of the small bowel in PE-positive
      patients in 78% of cases (18 of 23 patients). CONCLUSIONS: For endoscopic
      examination of the small bowel in patients with suspected mid-gastrointestinal
      bleeding, PPE is superior to PE with regard to the length of small bowel
      visualized, as well as the diagnostic yield. As the method also allows endoscopic
      treatment to be carried out, PPE should always be considered before open surgery
      and intraoperative endoscopy in patients with mid-gastrointestinal bleeding.

PMID- 16968509
TI  - Surgery or endoscopy for palliation of biliary obstruction due to metastatic
      pancreatic cancer.
AB  - BACKGROUND AND AIMS: Both endoscopic and surgical drainage procedures are
      effective palliative methods for malignant biliary obstruction. Surgical drainage
      is still preferred in developing countries due to the high cost of procuring
      metal biliary stents. The aim of this study was to evaluate the quality of life
      and the cost of care in patients with metastatic pancreatic cancer after
      endoscopic biliary drainage and surgical drainage. PATIENTS AND METHODS: This is
      a prospective, randomized controlled trial conducted in a tertiary referral
      center in Brazil. Patients with biliary obstruction due to metastatic pancreatic
      cancer and liver metastasis, but without gastric outlet obstruction, were
      included in the study. Endoscopic biliary drainage with the insertion of a metal
      stent into the bile duct was compared with the surgical drainage procedure
      (choledochojejunostomy and gastrojejunostomy). Quality of life was assessed
      before, and 30 days, 60 days, and 120 days after the drainage procedure. The cost
      of drainage procedure, cost during the first 30 days and the total cost from
      drainage procedure to death were calculated. RESULTS: Of the 273 patients with
      pancreatic malignancy seen at our hospital between July 2001 and October 2004, 35
      patients were eligible for the study, and 30 agreed to participate in the study.
      Both surgical and endoscopic drainage procedures were successful, without any
      mortality in the first 30 days. The cost of biliary drainage procedure (US
      dollars 2,832 +/- 519 vs 3,821 +/- 1,181, p= 0.031), the cost of care during the
      first 30 days after drainage (US dollars 3,122 +/- 877 vs 6,591 +/- 711, p=
      0.001), and the overall total cost of care that included initial care and
      subsequent interventions and hospitalizations until death (US dollars 4,271+/-
      2,411 vs 8,321 +/- 1,821, p= 0.0013) were lower in the endoscopy group compared
      with the surgical group. In addition, the quality of life scores were better in
      the endoscopy group at 30 days (p= 0.042) and 60 days (p= 0.05). There was no
      difference between the two groups in complication rate, readmissions for
      complications, and duration of survival. CONCLUSIONS: Endoscopic biliary drainage
      is cheaper and provides better quality of life in patients with biliary
      obstruction and metastatic pancreatic cancer.

PMID- 16968510
TI  - Treatment alternatives for hepatitis B cirrhosis: a cost-effectiveness analysis.
AB  - BACKGROUND: Hepatitis B virus (HBV) patients with cirrhosis are at risk for
      developing costly, morbid, or mortal events, and therefore need highly effective
      therapies. Lamivudine is effective but is limited by viral resistance. In
      contrast, adefovir and entecavir have lower viral resistance, but are more
      expensive. The most cost-effective approach is uncertain. METHODS: We evaluated
      the cost-effectiveness of six strategies in HBV cirrhosis: (1) No HBV treatment
      ("do nothing"), (2) lamivudine monotherapy, (3) adefovir monotherapy, (4)
      lamivudine with crossover to adefovir on resistance ("adefovir salvage"), (5)
      entecavir monotherapy, or (6) lamivudine with crossover to entecavir on
      resistance ("entecavir salvage"). The primary outcome was the incremental cost
      per quality-adjusted life-year (QALY) gained. RESULTS: The "do nothing" strategy
      was least effective yet least expensive. Compared with "do nothing," using
      adefovir cost an incremental US dollars 19,731. Entecavir was more effective yet
      more expensive than adefovir, and cost an incremental US dollars 25,626 per QALY
      gained versus adefovir. Selecting between entecavir versus adefovir was highly
      dependent on the third-party payer's "willingess-to-pay" (e.g., 45% and 60% of
      patients fall within budget if willing-to-pay US dollars 10K and US dollars 50K
      per QALY gained for entecavir, respectively). Both lamivudine monotherapy and the
      "salvage" strategies were not cost-effective. However, between the two salvage
      strategies, "adefovir salvage" was more effective and less expensive than
      "entecavir salvage." CONCLUSION: Both entecavir and adefovir are cost-effective
      in patients with HBV cirrhosis. Choosing between adefovir and entecavir is highly
      dependent on available budgets. In patients with HBV cirrhosis with previous
      lamivudine resistance, "adefovir salvage" appears more effective and less
      expensive than "entecavir salvage."

PMID- 16968511
TI  - Inconsistencies in endoscope-reprocessing and infection-control guidelines: the
      importance of endoscope drying.
AB  - INTRODUCTION: Endoscope reprocessing is a multi-stepped process that renders a
      contaminated endoscope safe for reuse. Its steps include meticulous cleaning,
      complete immersion in a liquid chemical sterilant (LCS) or disinfectant to
      achieve high-level disinfection (or "liquid sterilization"), water rinsing, and
      proper handling and storage. Surveys and reports indicate that not all health
      care facilities dry their endoscopes after reprocessing. Endoscope drying can be
      easily, quickly, and inexpensively achieved by flushing the endoscope's internal
      channels, and wiping its external surfaces, with 70-90% ethyl or isopropyl
      alcohol, to facilitate drying after reprocessing, followed by compressed or
      forced air. METHODS: The medical literature was reviewed to evaluate the
      importance of endoscope drying to the prevention of disease transmission. Several
      national and international endoscope-reprocessing and infection-control
      guidelines and a public health advisory were also reviewed and compared for
      consistency and to evaluate the emphasis each places on endoscope drying. If a
      guideline recommends endoscope drying, this study clarified whether this step is
      recommended after reprocessing throughout the day (i.e., between patient
      procedures), before storage, or both. These guidelines were also reviewed to
      determine whether any of them recommend reprocessing endoscopes before the first
      patient of the day. RESULTS: This review identified several published reports and
      clinical studies that demonstrate the significant contribution of endoscope
      drying to the prevention of disease transmission. This review also identified
      significant differences and inconsistencies regarding the emphasis different
      published guidelines and a public health advisory place on endoscope drying. Some
      guidelines recommend drying the endoscope after completion of every reprocessing
      cycle, both throughout the day and before storage, while others deemphasize its
      importance and recommend endoscope drying only before storage, if at all. Instead
      of recommending endoscope drying before storage, some guidelines recommend
      reprocessing endoscopes before the first patient of the day. DISCUSSION AND
      CONCLUSION: The finding that several guidelines are inconsistent with one another
      and that some are remiss and fail to recommend endoscope drying is of concern.
      Endoscope drying is as important to the prevention of nosocomial infection as
      cleaning and high-level disinfection (or "liquid sterilization"). Whereas wet or
      inadequately dried endoscopes pose an increased risk of contamination and have
      been associated with transmission of waterborne microorganisms and nosocomial
      infection, thoroughly dried (and properly cleaned and high-level disinfected)
      endoscopes have not been linked to nosocomial infection. Moreover, inconsistent
      guidelines can confuse reprocessing staff members and result in noncompliance,
      variations in the standard of care, and ineffective reprocessing. To minimize the
      risk of disease transmission and nosocomial infection, modification and revision
      of guidelines are recommended as required to be consistent with one another and
      to unconditionally recommend endoscope drying after completion of every
      reprocessing cycle, both between patient procedures and before storage, no matter
      the label claim of the LCS or disinfectant, the label claim of the automated
      reprocessing system, or the microbial quality of the rinse water. According to
      the medical literature, adoption of this recommendation may reduce the importance
      of not only monitoring the microbial quality of the rinse water, but also
      reprocessing endoscopes before the first patient of the day, both of which can be
      costly practices that a few guidelines recommend.

PMID- 16968512
TI  - Transjugular Intrahepatic Portosystemic Shunt (TIPS), the preferred therapeutic
      option for Budd Chiari syndrome associated with portal vein thrombosis.

PMID- 16968514
TI  - Diet and dyspepsia: to believe patients or studies?

PMID- 16968516
TI  - Crohn's disease in common variable immunodeficiency: treatment with antitumor
      necrosis factor alpha.

PMID- 16968517
TI  - Baclofen facilitates PEG placement in paraplegia-in-flexion syndrome.

PMID- 16968518
TI  - A psoas abscess caused by Pseudomonas aeruginosa due to diverticular perforation.

PMID- 16968522
TI  - Comparative transcript and alkaloid profiling in Papaver species identifies a
      short chain dehydrogenase/reductase involved in morphine biosynthesis.
AB  - Plants of the order Ranunculales, especially members of the species Papaver,
      accumulate a large variety of benzylisoquinoline alkaloids with about 2500
      structures, but only the opium poppy (Papaver somniferum) and Papaver setigerum
      are able to produce the analgesic and narcotic morphine and the antitussive
      codeine. In this study, we investigated the molecular basis for this exceptional
      biosynthetic capability by comparison of alkaloid profiles with gene expression
      profiles between 16 different Papaver species. Out of 2000 expressed sequence
      tags obtained from P. somniferum, 69 show increased expression in morphinan
      alkaloid-containing species. One of these cDNAs, exhibiting an expression pattern
      very similar to previously isolated cDNAs coding for enzymes in
      benzylisoquinoline biosynthesis, showed the highest amino acid identity to
      reductases in menthol biosynthesis. After overexpression, the protein encoded by
      this cDNA reduced the keto group of salutaridine yielding salutaridinol, an
      intermediate in morphine biosynthesis. The stereoisomer 7-epi-salutaridinol was
      not formed. Based on its similarities to a previously purified protein from P.
      somniferum with respect to the high substrate specificity, molecular mass and
      kinetic data, the recombinant protein was identified as salutaridine reductase
      (SalR; EC 1.1.1.248). Unlike codeinone reductase, an enzyme acting later in the
      pathway that catalyses the reduction of a keto group and which belongs to the
      family of the aldo-keto reductases, the cDNA identified in this study as SalR
      belongs to the family of short chain dehydrogenases/reductases and is related to
      reductases in monoterpene metabolism.

PMID- 16968523
TI  - Transition from purkinje fiber-related rapid polymorphic ventricular tachycardia
      to sustained monomorphic ventricular tachycardia in a patient with a structurally
      normal heart: a case report.
AB  - We describe a 17-year-old woman with a structurally normal heart in which short
      sustained rapid polymorphic ventricular tachycardias (VTs) were repetitively
      provoked by an antiarrhythmic agent, pilsicainide, and spontaneously changed into
      a sustained monomorphic VT. The latter was terminated by verapamil and was shown
      to be due to reentry by entrainment. Those two VTs originated from the Purkinje
      fibers in the left ventricular septum. Radiofrequency catheter ablation guided by
      the diastolic double potentials eliminated both VTs. Neither tachycardia recurred
      over a 5-month follow-up period or during antiarrhythmic drug challenge tests at
      1 week, 1 month, and 3 months after the ablation.

PMID- 16968525
TI  - Transthoracic tissue Doppler imaging of the atria: a novel method to determine
      the atrial fibrillation cycle length.
AB  - BACKGROUND: The atrial fibrillation cycle length (AFCL) is a critical parameter
      for the perpetuation and termination of AF. In the present study, we evaluated a
      new method to measure the AFCL based on transthoracic tissue Doppler imaging
      (TDI) of the right atrium (RA) and left atrium (LA). METHODS: Twenty patients
      with AF (6 acute AF, 14 persistent or permanent AF) were studied. A quadripolar
      catheter was positioned at RA or LA to measure AFCL (AFCL(EGM), gold standard).
      Transthoracic echocardiography (apical 4-chamber view) was used to perform pulsed
      wave TDI at the free wall of RA or LA. AFCL(TDI) was defined as the time interval
      between two consecutive positive to negative crossings of the baseline of the
      atrial time velocity curves. AFCL(EGM) and AFCL(TDI) were measured at baseline
      and during a 10-minute infusion of flecainide (1.5 mg/kg). RESULTS: Measurement
      of AFCL(TDI) was feasible in all but one patient. At baseline, AFCL(EGM) was 170
      +/- 22 ms, AFCL(TDI) 172 +/- 22 ms (difference 2 +/- 5 ms). AFCL(TDI) correlated
      significantly with AFCL(EGM) (R = 0.91, P < 0.0001). Bland-Altman analysis showed
      a bias of -2 ms with a 95% limit of agreement between -26 ms and +22 ms. During
      flecainide, the AFCL(TDI) method yielded an AFCL prolongation from 176 +/- 23 ms
      at baseline to 279 +/- 68 ms (P < 0.01) after 10 minutes of infusion (57 +/-
      26%). CONCLUSIONS: (1) Tissue Doppler imaging of the atria during transthoracic
      echocardiography can be used to reliably determine the AFCL during both acute and
      persistent or permanent AF. (2) Continuous measurement of AFCL with TDI can be
      used to monitor the effect of antiarrhythmic drugs on atrial rate during AF. (3)
      This novel method is attractive because of the ease of acquiring the data and its
      noninvasive character.

PMID- 16968526
TI  - Safety concerns on the development of novel therapeutic drugs.
AB  - Along with recent innovative approaches resulting in the development of new
      therapies such as small molecular inhibitors, therapeutic antibodies, recombinant
      proteins and gene therapy, there is increasing need for improved understanding of
      the basic molecular mechanisms that are exploited by such treatments. Helpful
      tools in the analysis of drug effects include high-throughput screening
      techniques such as microarrays, which are used in transcriptomics and
      pharmacogenomics. Although we are far from using these extensive and costly tests
      in our daily clinical routine, their application in basic research nevertheless
      takes us closer to individualized therapeutic strategies, in which the optimal
      therapeutic regimen is identified for each individual patient.

PMID- 16968527
TI  - Localization studies of two white spot syndrome virus structural proteins VP51
      and VP76.
AB  - VP51 and VP76 are two structural proteins of white spot syndrome virus (WSSV).
      However, there is some controversy about their localization in the virion at
      present. In this study, we employ multiple approaches to reevaluate the location
      of VP51 and VP76. Firstly, we found VP51 and VP76 presence in viral nucleocapsids
      fraction by Western blotting. Secondly, after the high-salt treatment of
      nucleocapsids, VP51 and VP76 were still exclusively present in viral capsids by
      Western blotting and immunoelectron microscopy, suggesting two proteins are
      structural components of the viral capsid. To gather more evidence, we developed
      a method based on immunofluorescence flow cytometry. The results revealed that
      the mean fluorescence intensity of the viral capsids group was significantly
      higher than that of intact virions group after incubation with anti-VP51 or anti
      VP76 serum and fluorescein isothiocyanate conjugated secondary antibody. All
      these results indicate that VP51 and VP76 are both capsid proteins of WSSV.

PMID- 16968528
TI  - Binge eating symptomatology in overweight and obese patients with schizophrenia:
      a case control study.
AB  - OBJECTIVE: The purpose of this study was to assess whether severe overweight
      schizophrenic treated patients differ from controls and from pairs in binge
      eating symptomatology. METHOD: Current body mass index (BMI) and the binge eating
      status were assessed cross-sectionally in 40 schizophrenic outpatients and 40 non
      psychiatric controls. In each group half of the subjects were severe overweight
      (BMI > or = 28) or obese. RESULTS: Pearson Chi-square analysis shows a higher
      number of subjects with binge symptomatology in the group of patients with
      schizophrenia having BMI > or = 28 (Pearson Chi-square = 8.67, p = 0.034). Among
      subjects with BMI > or = 28, 60% of patients with schizophrenia and 30% of
      controls have binge eating symptomatology. CONCLUSION: This result may odds to
      the understanding of weight gain associated with antipsychotics and underscores
      the importance of assessing binge eating behaviour during treatment and
      prevention of obesity in this population.

PMID- 16968529
TI  - Development of an in vitro model to study clot lysis activity of thrombolytic
      drugs.
AB  - BACKGROUND: Thrombolytic drugs are widely used for the management of cerebral
      venous sinus thrombosis patients. Several in vitro models have been developed to
      study clot lytic activity of thrombolytic drugs, but all of these have certain
      limitations. There is need of an appropriate model to check the clot lytic
      efficacy of thrombolytic drugs. In the present study, an attempt has been made to
      design and develop a new model system to study clot lysis in a simplified and
      easy way using a thrombolytic drug, streptokinase. METHODS: Whole blood from
      healthy individuals (n = 20) was allowed to form clots in a pre-weighed sterile
      microcentrifuge tubes; serum was removed and clot was weighed. After lysis by
      streptokinase fluid was removed and remnants of clot were again weighed along
      with the tube. Percentage of Clot lysis was calculated on the basis of the weight
      difference of microcentrifuge tubes obtained before and after clot lysis.
      RESULTS: There was a significant percentage of clot lysis observed when
      streptokinase was used. On the other hand with water (negative control), minimal
      (2.5%) clot lysis was observed. There was a significant difference between clot
      lysis done by streptokinase and water. CONCLUSION: Our study could be a rapid and
      effective methodology to study clot-lytic effect of newly developed drugs as well
      as known drugs.

PMID- 16968530
TI  - Lessons from a small country about the global obesity crisis.
AB  - Developed countries had high obesity rates before the problem was taken seriously
      and hence the genesis must be seen in retrospect. Developing countries offer a
      clear view of causal factors but also opportunities for prevention, which must
      focus on both food and physical activity environments.

PMID- 16968531
TI  - Genome-wide DNA polymorphism analyses using VariScan.
AB  - BACKGROUND: DNA sequence polymorphisms analysis can provide valuable information
      on the evolutionary forces shaping nucleotide variation, and provides an insight
      into the functional significance of genomic regions. The recent ongoing genome
      projects will radically improve our capabilities to detect specific genomic
      regions shaped by natural selection. Current available methods and software,
      however, are unsatisfactory for such genome-wide analysis. RESULTS: We have
      developed methods for the analysis of DNA sequence polymorphisms at the genome
      wide scale. These methods, which have been tested on a coalescent-simulated and
      actual data files from mouse and human, have been implemented in the VariScan
      software package version 2.0. Additionally, we have also incorporated a graphical
      user interface. The main features of this software are: i) exhaustive population
      genetic analyses including those based on the coalescent theory; ii) analysis
      adapted to the shallow data generated by the high-throughput genome projects;
      iii) use of genome annotations to conduct a comprehensive analyses separately for
      different functional regions; iv) identification of relevant genomic regions by
      the sliding-window and wavelet-multiresolution approaches; v) visualization of
      the results integrated with current genome annotations in commonly available
      genome browsers. CONCLUSION: VariScan is a powerful and flexible suite of
      software for the analysis of DNA polymorphisms. The current version implements
      new algorithms, methods, and capabilities, providing an important tool for an
      exhaustive exploratory analysis of genome-wide DNA polymorphism data.

PMID- 16968532
TI  - Occupational injury proneness in Indian women: a survey in fish processing
      industries.
AB  - A cross sectional survey was initiated to understand the frequency of
      occupational injury occurrence and the associated factors in the fish processing
      industries of western India involving 185 randomly selected women subjects. All
      the subjects were interviewed with the help of an interviewer-administered
      questionnaire to collect information regarding their personal, occupational and
      work related morbidity details (including details of occupational injuries).
      Logistic regression method was used to analyze the data in order to obtain the
      contribution of individual factors on occupational injuries. This study has shown
      that work related morbidity like blanching of hand (OR; 2.30, 95%CI; 1.12-4.74)
      and nature of job like grading (OR; 3.99, 95%CI; 1.41-11.27) and packing (OR;
      5.68, 95%CI; 1.65-19.57) had a significant impact on injury causation. This study
      eventually concludes that apart from nature of job of fish processing workers
      occupational hazards prevailing in the work environment contribute significantly
      to the occurrence of work related injuries and prevention of such occupational
      hazards may help in protecting workers from occupational injuries also.

PMID- 16968533
TI  - The human ortholog of the rodent testis-specific ABC transporter Abca17 is a
      ubiquitously expressed pseudogene (ABCA17P) and shares a common 5' end with
      ABCA3.
AB  - BACKGROUND: During the past years, we and others discovered a series of human ATP
      binding cassette (ABC) transporters, now referred to as ABC A-subfamily
      transporters. Recently, a novel testis-specific ABC A transporter, Abca17, has
      been cloned in rodent. In this study, we report the identification and
      characterization of the human ortholog of rodent Abca17. RESULTS: The novel human
      ABC A-transporter gene on chromosome 16p13.3 is ubiquitously expressed with
      highest expression in glandular tissues and the heart. The new ABC transporter
      gene exhibits striking nucleotide sequence homology with the recently cloned
      mouse (58%) and rat Abca17 (51%), respectively, and is located in the syntenic
      region of mouse Abca17 indicating that it represents the human ortholog of rodent
      Abca17. However, unlike in the mouse, the full-length ABCA17 transcript (4.3 kb)
      contains numerous mutations that preclude its translation into a bona fide ABC
      transporter protein strongly suggesting that the human ABCA17 gene is a
      transcribed pseudogene (ABCA17P). We identified numerous alternative ABCA17P
      splice variants which are transcribed from two distinct transcription initiation
      sites. Genomic analysis revealed that ABCA17P borders on another ABC A-subfamily
      transporter - the lung surfactant deficiency gene ABCA3. Surprisingly, we found
      that both genes overlap at their first exons and are transcribed from opposite
      strands. This genomic colocalization and the observation that the ABCA17P and
      ABCA3 genes share significant homologies in several exons (up to 98%) suggest
      that both genes have evolved by gene duplication. CONCLUSION: Our results
      demonstrate that ABCA17P and ABCA3 form a complex of overlapping genes in the
      human genome from which both non-coding and protein-coding ABC A-transporter RNAs
      are expressed. The fact that both genes overlap at their 5' ends suggests
      interdependencies in their regulation and may have important implications for the
      functional analysis of the disease gene ABCA3. Moreover, this is the first
      demonstration of the expression of a pseudogene and its parent gene from a common
      overlapping DNA region in the human genome.

PMID- 16968535
TI  - The mother-child nexus. Knowledge and valuation of wild food plants in Wayanad,
      Western Ghats, India.
AB  - This study focuses on the mother-child nexus (or process of enculturation) with
      respect to knowledge and valuation of wild food plants in a context where
      accelerated processes of modernization and acculturation are leading to the
      erosion of knowledge and cultural values associated with wild food plant use, in
      Wayanad, Western Ghats, India. Wild food plants in this biodiversity hotspot form
      an important part of local diets and are used as famine foods and medicines. In
      general, the collection and consumption of these foods are increasingly
      stigmatized as symbols of poverty and 'tribalness' (equivalent to
      'backwardness'). The study, which falls within the discipline of ethnobotany,
      involves three socio-cultural groups--the Paniya and Kuruma tribes and non
      tribals. Further, it examines the impact in the enculturation process of an
      unusual educational programme sponsored by the MS Swaminathan Research Foundation
      that is oriented towards creating awareness among children of cultural identity
      and local biological resources--the study compares children having participated
      in the programme with those who have not, with their mothers. The process of
      enculturation is assessed by comparing wild food plant knowledge and values
      between mothers and their children, and by examining events where knowledge
      transmission occurs, including collection and consumption. For that, quantitative
      and qualitative data collection and analysis tools were used, and methods
      included semi-structured interviews, photo identification and informal interviews
      of key informants. Results ratify that women are the knowledge holders and are
      the primary means of knowledge transmission to their children. Nevertheless,
      fewer children are collecting wild food plants with mothers and learning about
      them, apparently because of children's lack of time. On the other hand, older
      people acknowledge that a "change in taste" is occurring among younger
      generations. In general, there is a simultaneous transmission from mothers to
      children of contrasting values pertaining to wild food plants: that they are
      'good food' but also that they are symbols of low status and poverty, leading to
      feelings of shame and inferiority. Finally, the study concludes that the
      educational programme, through a "learning by doing" approach counteracts social
      stigma and encourages learning among children of all ages and socio-cultural
      groups, particularly stimulating non-tribal children to learn from tribals.

PMID- 16968534
TI  - A biological question and a balanced (orthogonal) design: the ingredients to
      efficiently analyze two-color microarrays with Confirmatory Factor Analysis.
AB  - BACKGROUND: Factor analysis (FA) has been widely applied in microarray studies as
      a data-reduction-tool without any a-priori assumption regarding associations
      between observed data and latent structure (Exploratory Factor Analysis).A
      disadvantage is that the representation of data in a reduced set of dimensions
      can be difficult to interpret, as biological contrasts do not necessarily
      coincide with single dimensions. However, FA can also be applied as an instrument
      to confirm what is expected on the basis of pre-established hypotheses
      (Confirmatory Factor Analysis, CFA). We show that with a hypothesis incorporated
      in a balanced (orthogonal) design, including 'SelfSelf' hybridizations, dye swaps
      and independent replications, FA can be used to identify the latent factors
      underlying the correlation structure among the observed two-color microarray
      data. An orthogonal design will reflect the principal components associated with
      each experimental factor. We applied CFA to a microarray study performed to
      investigate cisplatin resistance in four ovarian cancer cell lines, which only
      differ in their degree of cisplatin resistance. RESULTS: Two latent factors,
      coinciding with principal components, representing the differences in cisplatin
      resistance between the four ovarian cancer cell lines were easily identified.
      From these two factors 315 genes associated with cisplatin resistance were
      selected, 199 genes from the first factor (False Discovery Rate (FDR): 19%) and
      152 (FDR: 24%) from the second factor, while both gene sets shared 36. The
      differential expression of 16 genes was validated with reverse transcription
      polymerase chain reaction. CONCLUSION: Our results show that FA is an efficient
      method to analyze two-color microarray data provided that there is a pre-defined
      hypothesis reflected in an orthogonal design.

PMID- 16968536
TI  - Improvement of lower extremity electrodiagnostic findings following a trial of
      spinal manipulation and motion-based therapy.
AB  - BACKGROUND: Lumbar disc herniation is a problem frequently encountered in manual
      medicine. While manual therapy has shown reasonable success in symptomatic
      management of these cases, little information is known how manual therapy may
      affect the structure and function of the lumbar disc itself. In cases where
      lumbar disc herniation is accompanied by radicular symptoms, electrodiagnostic
      testing has been used to provide objective clinical information on nerve
      function. This report examines the treatment rendered for a patient with lower
      extremity neurological deficit, as diagnosed on electrodiagnostic testing.
      Patient was treated using spinal manipulation and exercises performed on a
      Pettibon Wobble Chair, using electrodiagnostic testing as the primary outcome
      assessment. CASE PRESENTATION: An elderly male patient presented to a private
      spine clinic with right-sided foot drop. He had been prescribed an ankle-foot
      orthosis for this condition. All sensory, motor, and reflex findings in the right
      leg and foot were absent. This was validated on prior electromyography and nerve
      conduction velocity testing, performed by a board certified neurologist. Patient
      was treated using spinal manipulation twice-weekly and wobble chair exercises
      three times daily for 90 days total. Following this treatment, the patient was
      referred for follow-up electrodiagnostic studies. Significant improvements were
      made in these studies as well as self-rated daily function. CONCLUSION: Motion
      based therapies, as part of a comprehensive rehabilitation program, may
      contribute to the restoration of daily function and the reversal of neurological
      insult as detected by electrodiagnostic testing. Electrodiagnostic testing may be
      a useful clinical tool to evaluate the progress of chiropractic patients with
      lumbar disc herniation and radicular pain syndromes.

PMID- 16968537
TI  - Incidence of epidural haematoma and neurological injury in cardiovascular
      patients with epidural analgesia/anaesthesia: systematic review and meta
      analysis.
AB  - BACKGROUND: Epidural anaesthesia is used extensively for cardiothoracic and
      vascular surgery in some centres, but not in others, with argument over the
      safety of the technique in patients who are usually extensively anticoagulated
      before, during, and after surgery. The principle concern is bleeding in the
      epidural space, leading to transient or persistent neurological problems.
      METHODS: We performed an extensive systematic review to find published cohorts of
      use of epidural catheters during vascular, cardiac, and thoracic surgery, using
      electronic searching, hand searching, and reference lists of retrieved articles.
      RESULTS: Twelve studies included 14,105 patients, of whom 5,026 (36%) had
      vascular surgery, 4,971 (35%) cardiac surgery, and 4,108 (29%) thoracic surgery.
      There were no cases of epidural haematoma, giving maximum risks following
      epidural anaesthesia in cardiac, thoracic, and vascular surgery of 1 in 1,700, 1
      in 1,400 and 1 in 1,700 respectively. In all these surgery types combined the
      maximum expected rate would be 1 in 4,700. In all these patients combined there
      were eight cases of transient neurological injury, a rate of 1 in 1,700 (95%
      confidence interval 1 in 3,300 to 1 in 850). There were no cases of persistent
      neurological injury (maximum expected rate 1 in 4,600). CONCLUSION: These
      estimates for cardiothoracic epidural anaesthesia should be the worst case.
      Limitations are inadequate denominators for different types of surgery in
      anticoagulated cardiothoracic or vascular patients more at risk of bleeding.

PMID- 16968538
TI  - Hemolytic uremic syndrome following the infusion of oxaliplatin: case report.
AB  - BACKGROUND: Oxaliplatin is a platinum derivative, which is used in the treatment
      of colorectal cancer. A small number of oxaliplatin-related hemolytic and/or
      thrombocytopenic reactions have been reported. We present a case of hemolytic
      uremic syndrome that developed during the 4th cycle of combination chemotherapy
      with oxaliplatin, 5-fluorouracil and leucovorin. CASE PRESENTATION: A 52-year-old
      male was administered chemotherapy with oxaliplatin, 5-fluorouracil and
      leucovorin for a Duke's stage C colorectal carcinoma. Three cycles of
      chemotherapy had been administered without complications when, at the beginning
      of the fourth cycle, the patient developed clinical and laboratory abnormalities
      consistent with the development of the hemolytic-uremic syndrome. Treatment was
      discontinued; the patient was managed with monitored IV hydration and loop
      diuretics, high dose corticosteroids and fresh frozen plasma infusions and
      recovered completely. CONCLUSION: The hemolytic-uremic syndrome may be a rare
      complication of oxaliplatin-based chemotherapy. Clinicians need to maintain a
      high index of suspicion to diagnose and treat this life-threatening adverse
      event.

PMID- 16968539
TI  - Sex, bugs and Haldane's rule: the nematode genus Pristionchus in the United
      States.
AB  - BACKGROUND: The nematode Pristionchus pacificus has been developed as a satellite
      organism in evolutionary developmental biology for comparison to Caenorhabditis
      elegans. Comparative studies have revealed major differences in the regulation of
      developmental processes between P. pacificus and C. elegans. To place
      evolutionary developmental biology and the observed developmental differences
      between species in a comprehensive evolutionary context, such studies have to be
      complemented with ecological aspects. Knowledge about the ecology of the organism
      in question might indicate specific environmental conditions that can result in
      developmental adaptations and could account for species differences in
      development. To this end, we have started to investigate the ecology of
      Pristionchus nematodes. In recent field studies in Western Europe we found six
      Pristionchus species that are closely associated with scarab beetles and the
      Colorado potato beetle. This Pristionchus-beetle association provides the unique
      opportunity to combine research in evolutionary developmental biology with
      ecology. However, it remains unknown how general these findings from Europe are
      on a global scale. RESULTS: Here, we describe the Pristionchus species associated
      with scarab and Colorado potato beetles in the Eastern United States and show
      striking transatlantic differences and unexpected evolutionary and ecological
      patterns. Two hundred eighty of 285 (98%) isolates from American scarab beetles
      belong to five Pristionchus species, all of which are different from the European
      species. We describe four of them as novel Pristionchus species. The five
      American Pristionchus species fall into a single phylogenetic clade and have a
      male-female (gonochoristic) mode of reproduction, whereas the majority of
      European isolates are hermaphroditic. Crosses between the two most closely
      related species, P. aerivorus and P. pseudaerivorus n. sp., follow Haldane's rule
      in that heterogametic F1 males are inviable. We observed P. aerivorus and P.
      pseudaerivorus n. sp. coexisting on the same scarab beetle and obtained two cases
      of F1 hybrids from wild beetles. Finally, the Colorado potato beetle is
      associated with the same nematode, P. uniformis in the United States and Europe.
      Given the introduction of the Colorado potato beetle to Europe in 1877, our
      results suggest that P. uniformis was introduced together with its beetle vector.
      CONCLUSION: Taken together, the Pristionchus-beetle association provides a
      powerful tool for studying biodiversity, biogeography, speciation and species
      invasion on a global scale.

PMID- 16968540
TI  - Global similarity and local divergence in human and mouse gene co-expression
      networks.
AB  - BACKGROUND: A genome-wide comparative analysis of human and mouse gene expression
      patterns was performed in order to evaluate the evolutionary divergence of
      mammalian gene expression. Tissue-specific expression profiles were analyzed for
      9,105 human-mouse orthologous gene pairs across 28 tissues. Expression profiles
      were resolved into species-specific coexpression networks, and the topological
      properties of the networks were compared between species. RESULTS: At the global
      level, the topological properties of the human and mouse gene coexpression
      networks are, essentially, identical. For instance, both networks have topologies
      with small-world and scale-free properties as well as closely similar average
      node degrees, clustering coefficients, and path lengths. However, the human and
      mouse coexpression networks are highly divergent at the local level: only a small
      fraction (<10%) of coexpressed gene pair relationships are conserved between the
      two species. A series of controls for experimental and biological variance show
      that most of this divergence does not result from experimental noise. We further
      show that, while the expression divergence between species is genuinely rapid,
      expression does not evolve free from selective (functional) constraint. Indeed,
      the coexpression networks analyzed here are demonstrably functionally coherent as
      indicated by the functional similarity of coexpressed gene pairs, and this
      pattern is most pronounced in the conserved human-mouse intersection network.
      Numerous dense network clusters show evidence of dedicated functions, such as
      spermatogenesis and immune response, that are clearly consistent with the
      coherence of the expression patterns of their constituent gene members.
      CONCLUSION: The dissonance between global versus local network divergence
      suggests that the interspecies similarity of the global network properties is of
      limited biological significance, at best, and that the biologically relevant
      aspects of the architectures of gene coexpression are specific and particular,
      rather than universal. Nevertheless, there is substantial evolutionary
      conservation of the local network structure which is compatible with the notion
      that gene coexpression networks are subject to purifying selection.

PMID- 16968541
TI  - Hereditary thrombophilia.
AB  - Thrombophilia can be defined as a predisposition to form clots inappropriately.
      Thrombotic events during infancy and childhood are increasingly recognized as a
      significant source of mortality and morbidity. The predisposition to form clots
      can arise from genetic factors, acquired changes in the clotting mechanism, or,
      more commonly, an interaction between genetic and acquired factors. Since the
      turn of the last century, there has been extensive research focusing on both the
      genetic and acquired causes of thrombophilia, with particular focus on clotting
      events in the venous circulation. This review describes clinically relevant
      aspects of genetic venous thrombophilia, which include well-established, lesser
      known, and suggested causes of inherited thrombophilias.

PMID- 16968542
TI  - Lithium treatment and thyroid abnormalities.
AB  - BACKGROUND: Although the interactions between lithium treatment and thyroid
      function have long been recognised, their clinical relevance is still
      controversial. This paper sets out a review of the literature to date,
      considering that lithium still represents the gold standard among prophylactic
      treatments of manic-depression several decades after its introduction. METHOD:
      PubMed database was used to search for English-language articles relating to
      lithium treatment and thyroid function. As the amount of relevant papers totalled
      several hundreds, this review refers to previous reviews, especially with regard
      to older literature. Moreover, the authors particularly refer to a series of
      studies of thyroid function performed in a cohort of patients at different stages
      of lithium treatment, who were followed up by their group from 1989 onwards.
      RESULTS: The main findings from this review included: a) lithium definitely
      affects thyroid function as repeatedly shown by studies on cell cultures,
      experimental animals, volunteers, and patients; b) inhibition of thyroid hormone
      release is the critical mechanism in the development of hypothyroidism, goitre,
      and, perhaps, changes in the texture of the gland which are detected by
      ultrasonic scanning; c) compensatory mechanisms operate and prevent the
      development of hypothyroidism in the majority of patients; d) when additional
      risk factors are present, either environmental (such as iodine deficiency) or
      intrinsic (immunogenetic background), compensatory potential may be reduced and
      clinically relevant consequences may derive; e) hypothyroidism may develop in
      particular during the first years of lithium treatment, in middle-aged women, and
      in the presence of thyroid autoimmunity; f) thyroid autoimmunity is found in
      excess among patients suffering from affective disorders, irrespective of lithium
      exposure; g) in patients who have been on lithium for several years, the outcome
      of hypothyroidism, goitre, and thyroid autoimmunity do not much differ from those
      observed in the general population; h) hyperthyroidism and thyroid cancer are
      observed rarely during lithium treatment. RECOMMENDATIONS: Thyroid function tests
      (TSH, free thyroid hormones, specific antibodies, and ultrasonic scanning) should
      be performed prior to starting lithium prophylaxis. A similar panel should be
      repeated at one year. Thereafter, annual measurements of TSH may be sufficient to
      prevent overt hypothyroidism. In the presence of raised TSH or thyroid
      autoimmunity, shorter intervals between assessments are advisable (4-6 months).
      Measurement of antibodies and ultrasonic scanning may be repeated at 2-to-3-year
      intervals. The patient must be referred to the endocrinologist if TSH
      concentrations are repeatedly abnormal, and/or goitre or nodules are detected.
      Thyroid function abnormalities should not constitute an outright contraindication
      to lithium treatment, and lithium should not be stopped if a patient develops
      thyroid abnormalities. Decisions should be made taking into account the evidence
      that lithium treatment is perhaps the only efficient means of reducing the
      excessive mortality which is otherwise associated with affective disorders.

PMID- 16968543
TI  - Synthesis of acute phase proteins in rats with cirrhosis exposed to
      lipopolysaccharide.
AB  - BACKGROUND: In patients with cirrhosis, infection is frequent and a leading cause
      of death. This is secondary to various immunologic abnormalities in both the
      innate and the adaptive immune system. However, it remains unclear whether
      cirrhosis affects the inflammatory systemic component of the innate immunity,
      'the acute phase response', mostly effectuated by the liver itself. We
      hypothesized that rats with cirrhosis raise a reduced acute phase response
      induced by lipopolysaccharide (LPS). RESULTS: We examined the acute phase
      response induced by intraperitoneal injection of a low dose of LPS, in sham
      operated control animals and in rats with liver cirrhosis induced by bile duct
      ligation (BDL). We measured the serum concentrations of the most important acute
      phase proteins and their liver tissue gene expressions, assessed by mRNA levels.
      The BDL-model itself increased the serum concentration of alpha1-acid
      glycoprotein (alpha1AGP) and haptoglobin. LPS was lethal to 25% of the cirrhotic
      animals and to none of the controls. Twenty-four hours after LPS, the serum
      concentration of alpha1AGP and haptoglobin, the mRNA level of these acute phase
      proteins and of alpha2-macroglobulin and thiostatin rose to the same level in the
      animals with cirrhosis and in controls. CONCLUSION: In rats with experimental
      cirrhosis LPS caused high mortality. In the survivors, the cirrhotic liver still
      synthesized acute phase proteins as the normal liver, indicating a normal hepatic
      contribution to this part of the acute phase response.

PMID- 16968544
TI  - Fatal stroke after completion pneumonectomy for torsion of left upper lobe
      following left lower lobectomy.
AB  - BACKGROUND: The lobar torsion after lung surgery is a rare complication with an
      incidence of 0.09 to 0.4 %. It may occur after twisting of the bronchovascular
      pedicle of the remaining lobe after lobectomy, usually on the right side. The 180
      degree rotation of the pedicle produces an acute obstruction of the lobar
      bronchus (atelectasis) and of the lobar vessels as well. Without prompt treatment
      it progresses to lobar ischemia, pulmonary infarction and finally fatal gangrene.
      CASE PRESENTATION: A 62 years old female patient was admitted for surgical
      treatment of lung cancer. She underwent elective left lower lobectomy for
      squamous cell carcinoma (pT2 N0). The operation was unremarkable, and the patient
      was extubated in the operating room. After eight hours the patient established
      decrease of pO(2) and chest x-ray showed atelectasis of the lower lobe. To
      establish diagnosis, bronchoscopy was performed, demonstrating obstructed left
      lobar bronchus. The patient was re-intubated, and admitted to the operating room
      where reopening of the thoracotomy was performed. Lobar torsion was diagnosed,
      with the diaphragmatic surface of the upper lobe facing in an anterosuperior
      orientation. A completion pneumonectomy was performed. At the end of the
      procedure the patient developed a right pupil dilatation, presumably due to a
      cerebral embolism. A subsequent brain angio-CT scan established the diagnosis.
      She died at the intensive care unit 26 days later. CONCLUSION: The thoracic
      surgeon should suspect this rare early postoperative complication after any
      thoracic operation in every patient with atelectasis of the neighboring lobe.
      High index of suspicion and prompt diagnosis may prevent catastrophic
      consequences, such as, infarction or gangrene of the pulmonary lobe. During
      thoracic operations, especially whenever the lung or lobe hilum is full
      mobilized, fixation of the remaining lobe may prevent this life threatening
      complication.

PMID- 16968545
TI  - Hyperglycemia and nocturnal systolic blood pressure are associated with left
      ventricular hypertrophy and diastolic dysfunction in hypertensive diabetic
      patients.
AB  - BACKGROUND: The aim of this study was to determine if hypertensive type 2
      diabetic patients, when compared to patients with essential hypertension have an
      increased left ventricular mass index (LVMI) and a worse diastolic function, and
      if this fact would be related to 24-h pressoric levels changes. METHODS: Ninety
      one hypertensive patients with type 2 diabetes mellitus (DM) (group-1 [G1]), 59
      essential hypertensive patients (group-2 [G2]) and 26 healthy controls (group-3
      [G3]) were submitted to 24-h Ambulatory Blood Pressure Monitoring (ABPM) and
      echocardiography (ECHO) with Doppler. We calculated an average of fasting blood
      glucose (AFBG) values of G1 from the previous 4.2 years and a glycemic control
      index (GCI) (percentual of FBG above 200 mg/dl). RESULTS: G1 and G2 did not
      differ on average of diurnal systolic and diastolic BP. However, G1 presented
      worse diastolic function and a higher average of nocturnal systolic BP (NSBP) and
      LVMI (NSBP = 132 +/- 18 vs 124 +/- 14 mmHg; P < 0.05 and LVMI = 103 +/- 27 vs 89
      +/- 17 g/m2; P < 0.05, respectively). In G1, LVMI correlated with NSBP (r = 0.37;
      P < 0.001) and GCI (r = 0.29; P < 0.05) while NSBP correlated with GCI (r = 0.27;
      P < 0.05) and AFBG (r = 0.30; P < 0.01). When G1 was divided in tertiles
      according to NSBP, the subgroup with NSBP> or =140 mmHg showed a higher risk of
      LVH. Diabetics with NSBP> or =140 mmHg and AFBG>165 mg/dl showed an additional
      risk of LVH (P < 0.05; odds ratio = 11). In multivariate regression, both GCI and
      NSBP were independent predictors of LVMI in G1. CONCLUSION: This study suggests
      that hyperglycemia and higher NSBP levels should be responsible for an increased
      prevalence of LVH in hypertensive patients with Type 2 DM.

PMID- 16968546
TI  - Medulloblastoma outcome is adversely associated with overexpression of EEF1D,
      RPL30, and RPS20 on the long arm of chromosome 8.
AB  - BACKGROUND: Medulloblastoma is the most common malignant brain tumor of
      childhood. Improvements in clinical outcome require a better understanding of the
      genetic alterations to identify clinically significant biological factors and to
      stratify patients accordingly. In the present study, we applied cytogenetic
      characterization to guide the identification of biologically significant genes
      from gene expression microarray profiles of medulloblastoma. METHODS: We analyzed
      71 primary medulloblastomas for chromosomal copy number aberrations (CNAs) using
      comparative genomic hybridization (CGH). Among 64 tumors that we previously
      analyzed by gene expression microarrays, 27 were included in our CGH series. We
      analyzed clinical outcome with respect to CNAs and microarray results. We
      filtered microarray data using specific CNAs to detect differentially expressed
      candidate genes associated with survival. RESULTS: The most frequent lesions
      detected in our series involved chromosome 17; loss of 16q, 10q, or 8p; and gain
      of 7q or 2p. Recurrent amplifications at 2p23-p24, 2q14, 7q34, and 12p13 were
      also observed. Gain of 8q is associated with worse overall survival (p = 0.0141),
      which is not entirely attributable to MYC amplification or overexpression. By
      applying CGH results to gene expression analysis of medulloblastoma, we
      identified three 8q-mapped genes that are associated with overall survival in the
      larger group of 64 patients (p < 0.05): eukaryotic translation elongation factor
      1D (EEF1D), ribosomal protein L30 (RPL30), and ribosomal protein S20 (RPS20).
      CONCLUSION: The complementary use of CGH and expression profiles can facilitate
      the identification of clinically significant candidate genes involved in
      medulloblastoma growth. We demonstrate that gain of 8q and expression levels of
      three 8q-mapped candidate genes (EEF1D, RPL30, RPS20) are associated with adverse
      outcome in medulloblastoma.

PMID- 16968547
TI  - Complications after endovascular stent-grafting of thoracic aortic diseases.
AB  - BACKGROUND: To update our experience with thoracic aortic stent-graft treatment
      over a 5-year period, with special consideration for the occurrence and
      management of complications. METHODS: From December 2000 to June 2006, 52
      patients with thoracic aortic pathologies underwent endovascular repair; there
      were 43 males (83%) and 9 females, mean age 63 +/- 19 years (range 17-87).
      Fourteen patients (27%) were treated for degenerative thoracic aortic aneurysm,
      12 patients (24%) for penetrating aortic ulcer, 8 patients (15%) for blunt
      traumatic injury, 7 patients (13%) for acute type B dissection, 6 patients (11%)
      for a type B dissecting aneurysm; 5 patients (10%) with thoraco-abdominal aortic
      aneurysms were excluded from the analyses. Fifteen patients (32%) underwent
      emergency treatment. Overall, mean EuroSCORE was 9 +/- 3 (median 15, range 3-19).
      All procedures were performed in the theatre under general anesthesia. All
      complications occurring during hospitalisation were recorded. Follow-up protocol
      featured CT-A, and chest X-rays 1, 4 and 12 months after intervention, and
      annually thereafter. RESULTS: Primary technical success was achieved in all
      patients; procedures never aborted because of access difficulty. Conversion to
      standard open repair was never required. Mean duration of the procedure was 119
      +/- 75 minutes (median 90, range 45-285). Mean blood loss was 254 mL (range 50
      1200 mL). The mean length of the aorta covered by the SGs was 192 +/- 21 mm
      (range 100-360). The LSA was over-stented in 17 cases (17/47, 36%). Overall 30
      day operative mortality was 6.4% (3/47). Major complications included pneumonia
      (n = 9), cerebrovascular accidents (n = 4), arrhythmia (n = 4), acute renal
      failure (n = 3), and colic ischemia (n = 1). Overall, endoleak rate was 14%.
      CONCLUSION: Although this report is a retrospective and not comparative analysis
      of thoracic aortic repair, the combined minor and major morbidity rate was lower
      than previous reported to results of either electively and emergency performed
      conventional repair.

PMID- 16968548
TI  - Renal cell carcinoma presenting as a solitary cutaneous facial metastasis: case
      report and review of the literature.
AB  - BACKGROUND: Renal cell carcinoma is well known for its frequency to metastasise,
      particularly to lungs, liver, bones and brain. Metastasis to the skin is much
      less common. Presentation as a result of the skin lesion is even more unusual,
      with only 14 previously reported cases in the English literature. The majority of
      these cases have been reported in patients with recurrent disease or with other
      metastases. CASE PRESENTATION: We present only the second case of non-recurrent
      renal cell carcinoma with a solitary cutaneous facial metastasis reported in the
      English literature. CONCLUSION: Clinicians should conduct a careful inspection of
      the skin in patients with renal cell carcinoma and also have a high index of
      suspicion of primary internal organ malignancy in patients presenting with a skin
      lesion.

PMID- 16968549
TI  - Endogenous laminin is required for human airway smooth muscle cell maturation.
AB  - BACKGROUND: Airway smooth muscle (ASM) contraction underlies acute bronchospasm
      in asthma. ASM cells can switch between a synthetic-proliferative phenotype and a
      contractile phenotype. While the effects of extracellular matrix (ECM) components
      on modulation of ASM cells to a synthetic phenotype have been reported, the role
      of ECM components on maturation of ASM cells to a contractile phenotype in adult
      lung is unclear. As both changes in ECM components and accumulation of
      contractile ASM are features of airway wall remodelling in asthma, we examined
      the role of the ECM protein, laminin, in the maturation of contractile phenotype
      in human ASM cells. METHODS: Human ASM cells were made senescence-resistant by
      stable expression of human telomerase reverse transcriptase. Maturation to a
      contractile phenotype was induced by 7-day serum deprivation, as assessed by
      immunoblotting for desmin and calponin. The role of laminin on ASM maturation was
      investigated by comparing the effects of exogenous laminin coated on culture
      plates, and of soluble laminin peptide competitors. Endogenous expression of
      laminin chains during ASM maturation was also measured. RESULTS: Myocyte binding
      to endogenously expressed laminin was required for ASM phenotype maturation, as
      laminin competing peptides (YIGSR or GRGDSP) significantly reduced desmin and
      calponin protein accumulation that otherwise occurs with prolonged serum
      deprivation. Coating of plastic cell culture dishes with different purified
      laminin preparations was not sufficient to further promote accumulation of desmin
      or calponin during 7-day serum deprivation. Expression of alpha2, beta1 and
      gamma1 laminin chains by ASM cells was specifically up-regulated during myocyte
      maturation, suggesting a key role for laminin-2 in the development of the
      contractile phenotype. CONCLUSION: While earlier reports suggest exogenously
      applied laminin slows the spontaneous modulation of ASM to a synthetic phenotype,
      we show for the first time that endogenously expressed laminin is required for
      ASM maturation to the contractile phenotype. As endogenously expressed laminin
      chains alpha2, beta1 and gamma1 are uniquely increased during myocyte maturation,
      these laminin chains may be key in this process. Thus, human ASM maturation
      appears to involve regulated endogenous expression of a select set of laminin
      chains that are essential for accumulation of contractile phenotype myocytes.

PMID- 16968550
TI  - Uncoupling proteins, dietary fat and the metabolic syndrome.
AB  - There has been intense interest in defining the functions of UCP2 and UCP3 during
      the nine years since the cloning of these UCP1 homologues. Current data suggest
      that both UCP2 and UCP3 proteins share some features with UCP1, such as the
      ability to reduce mitochondrial membrane potential, but they also have distinctly
      different physiological roles. Human genetic studies consistently demonstrate the
      effect of UCP2 alleles on type-2 diabetes. Less clear is whether UCP2 alleles
      influence body weight or body mass index (BMI) with many studies showing a
      positive effect while others do not. There is strong evidence that both UCP2 and
      UCP3 protect against mitochondrial oxidative damage by reducing the production of
      reactive oxygen species. The evidence that UCP2 protein is a negative regulator
      of insulin secretion by pancreatic beta-cells is also strong: increased UCP2
      decreases glucose stimulated insulin secretion ultimately leading to beta-cell
      dysfunction. UCP2 is also neuroprotective, reducing oxidative stress in neurons.
      UCP3 may also transport fatty acids out of mitochondria thereby protecting the
      mitochondria from fatty acid anions or peroxides. Current data suggest that UCP2
      plays a role in the metabolic syndrome through down-regulation of insulin
      secretion and development of type-2 diabetes. However, UCP2 may protect against
      atherosclerosis through reduction of oxidative stress and both UCP2 and UCP3 may
      protect against obesity. Thus, these UCP1 homologues may both contribute to and
      protect from the markers of the metabolic syndrome.

PMID- 16968551
TI  - A chaotic view of behavior change: a quantum leap for health promotion.
AB  - BACKGROUND: The study of health behavior change, including nutrition and physical
      activity behaviors, has been rooted in a cognitive-rational paradigm. Change is
      conceptualized as a linear, deterministic process where individuals weigh pros
      and cons, and at the point at which the benefits outweigh the cost change occurs.
      Consistent with this paradigm, the associated statistical models have almost
      exclusively assumed a linear relationship between psychosocial predictors and
      behavior. Such a perspective however, fails to account for non-linear, quantum
      influences on human thought and action. Consider why after years of false starts
      and failed attempts, a person succeeds at increasing their physical activity,
      eating healthier or losing weight. Or, why after years of success a person
      relapses. This paper discusses a competing view of health behavior change that
      was presented at the 2006 annual ISBNPA meeting in Boston. DISCUSSION: Rather
      than viewing behavior change from a linear perspective it can be viewed as a
      quantum event that can be understood through the lens of Chaos Theory and Complex
      Dynamic Systems. Key principles of Chaos Theory and Complex Dynamic Systems
      relevant to understanding health behavior change include: 1) Chaotic systems can
      be mathematically modeled but are nearly impossible to predict; 2) Chaotic
      systems are sensitive to initial conditions; 3) Complex Systems involve multiple
      component parts that interact in a nonlinear fashion; and 4) The results of
      Complex Systems are often greater than the sum of their parts. Accordingly, small
      changes in knowledge, attitude, efficacy, etc may dramatically alter motivation
      and behavioral outcomes. And the interaction of such variables can yield almost
      infinite potential patterns of motivation and behavior change. In the linear
      paradigm unaccounted for variance is generally relegated to the catch all "error"
      term, when in fact such "error" may represent the chaotic component of the
      process. The linear and chaotic paradigms are however, not mutually exclusive, as
      behavior change may include both chaotic and cognitive processes. Studies of
      addiction suggest that many decisions to change are quantum rather than planned
      events; motivation arrives as opposed to being planned. Moreover, changes made
      through quantum processes appear more enduring than those that involve more
      rational, planned processes. How such processes may apply to nutrition and
      physical activity behavior and related interventions merits examination.

PMID- 16968552
TI  - A prospective, multi-method, multi-disciplinary, multi-level, collaborative,
      social-organisational design for researching health sector accreditation
      [LP0560737].
AB  - BACKGROUND: Accreditation has become ubiquitous across the international health
      care landscape. Award of full accreditation status in health care is viewed, as
      it is in other sectors, as a valid indicator of high quality organisational
      performance. However, few studies have empirically demonstrated this assertion.
      The value of accreditation, therefore, remains uncertain, and this persists as a
      central legitimacy problem for accreditation providers, policymakers and
      researchers. The question arises as to how best to research the validity, impact
      and value of accreditation processes in health care. Most health care
      organisations participate in some sort of accreditation process and thus it is
      not possible to study its merits using a randomised controlled strategy. Further,
      tools and processes for accreditation and organisational performance are
      multifaceted. METHODS/DESIGN: To understand the relationship between them a multi
      method research approach is required which incorporates both quantitative and
      qualitative data. The generic nature of accreditation standard development and
      inspection within different sectors enhances the extent to which the findings of
      in-depth study of accreditation process in one industry can be generalised to
      other industries. This paper presents a research design which comprises a
      prospective, multi-method, multi-level, multi-disciplinary approach to assess the
      validity, impact and value of accreditation. DISCUSSION: The accreditation
      program which assesses over 1,000 health services in Australia is used as an
      exemplar for testing this design. The paper proposes this design as a framework
      suitable for application to future international research into accreditation. Our
      aim is to stimulate debate on the role of accreditation and how to research it.

PMID- 16968553
TI  - Leishmania isoenzyme polymorphisms in Ecuador: relationships with geographic
      distribution and clinical presentation.
AB  - BACKGROUND: Determinants of the clinical presentation of the leishmaniases are
      poorly understood but Leishmania species and strain differences are important. To
      examine the relationship between clinical presentation, species and isoenzyme
      polymorphisms, 56 Leishmania isolates from distinct presentations of American
      tegumentary leishmaniasis (ATL) from Ecuador were analyzed. METHODS: Isolates
      were characterized by multilocus enzyme electrophoresis for polymorphisms of 11
      isoenzymes. Patients were infected in four different ecologic regions: highland
      and lowland jungle of the Pacific coast, Amazonian lowlands and Andean highlands.
      RESULTS: Six Leishmania species constituting 21 zymodemes were identified: L.
      (Viannia) panamensis (21 isolates, 7 zymodemes), L. (V.) guyanensis (7 isolates,
      4 zymodemes), L. (V.) braziliensis (5 isolates, 3 zymodemes), L. (Leishmania)
      mexicana (11 isolates, 4 zymodemes), L. (L.) amazonensis (10 isolates, 2
      zymodemes) and L. (L.) major (2 isolates, 1 zymodeme). L. panamensis was the
      species most frequently identified in the Pacific region and was associated with
      several clinical variants of cutaneous disease (CL); eight cases of leishmaniasis
      recidiva cutis (LRC) found in the Pacific highlands were associated with 3
      zymodemes of this species. Mucocutaneous leishmaniasis found only in the
      Amazonian focus was associated with 3 zymodemes of L. braziliensis. The papular
      variant of CL, Uta, found in the Andean highlands was related predominantly with
      a single zymodeme of L. mexicana. CONCLUSION: Our data show a high degree of
      phenotypic variation within species, and some evidence for associations between
      specific variants of ATL (i.e. Uta and LRC) and specific Leishmania zymodemes.
      This study further defines the geographic distribution of Leishmania species and
      clinical variants of ATL in Ecuador.

PMID- 16968554
TI  - A comparison of methods for calculating population exposure estimates of daily
      weather for health research.
AB  - BACKGROUND: To explain the possible effects of exposure to weather conditions on
      population health outcomes, weather data need to be calculated at a level in
      space and time that is appropriate for the health data. There are various ways of
      estimating exposure values from raw data collected at weather stations but the
      rationale for using one technique rather than another; the significance of the
      difference in the values obtained; and the effect these have on a research
      question are factors often not explicitly considered. In this study we compare
      different techniques for allocating weather data observations to small
      geographical areas and different options for weighting averages of these
      observations when calculating estimates of daily precipitation and temperature
      for Australian Postal Areas. Options that weight observations based on distance
      from population centroids and population size are more computationally intensive
      but give estimates that conceptually are more closely related to the experience
      of the population. RESULTS: Options based on values derived from sites internal
      to postal areas, or from nearest neighbour sites--that is, using proximity
      polygons around weather stations intersected with postal areas--tended to include
      fewer stations' observations in their estimates, and missing values were common.
      Options based on observations from stations within 50 kilometres radius of
      centroids and weighting of data by distance from centroids gave more complete
      estimates. Using the geographic centroid of the postal area gave estimates that
      differed slightly from the population weighted centroids and the population
      weighted average of sub-unit estimates. CONCLUSION: To calculate daily weather
      exposure values for analysis of health outcome data for small areas, the use of
      data from weather stations internal to the area only, or from neighbouring
      weather stations (allocated by the use of proximity polygons), is too limited.
      The most appropriate method conceptually is the use of weather data from sites
      within 50 kilometres radius of the area weighted to population centres, but a
      simpler acceptable option is to weight to the geographic centroid.

PMID- 16968555
TI  - The early responses of VEGF and its receptors during acute lung injury:
      implication of VEGF in alveolar epithelial cell survival.
AB  - INTRODUCTION: The function of the vascular endothelial growth factor (VEGF)
      system in acute lung injury (ALI) is controversial. We hypothesized that the role
      of VEGF in ALI may depend upon the stages of pathogenesis of ALI. METHODS: To
      determine the responses of VEGF and its receptors during the early onset of ALI,
      C57BL6 mice were subjected to intestinal ischemia or sham operation for 30
      minutes followed by intestinal ischemia-reperfusion (IIR) for four hours under
      low tidal volume ventilation with 100% oxygen. The severity of lung injury,
      expression of VEGF and its receptors were assessed. To further determine the role
      of VEGF and its type I receptor in lung epithelial cell survival, human lung
      epithelial A549 cells were treated with small interference RNA (siRNA) to
      selectively silence related genes. RESULTS: IIR-induced ALI featured interstitial
      inflammation, enhancement of pulmonary vascular permeability, increase of total
      cells and neutrophils in the bronchoalveolar lavage (BAL), and alveolar
      epithelial cell death. In the BAL, VEGF was significantly increased in both sham
      and IIR groups, while the VEGF and VEGF receptor (VEGFR)-1 in the lung tissues
      were significantly reduced in these two groups. The increase of VEGF in the BAL
      was correlated with the total protein concentration and cell count. Significant
      negative correlations were observed between the number of VEGF or VEGFR-1
      positive cells, and epithelial cells undergoing cell death. When human lung
      epithelial A549 cells were pre-treated with 50 nM of siRNA either against VEGF or
      VEGFR-1 for 24 hours, reduced VEGF and VEGFR-1 levels were associated with
      reduced cell viability. CONCLUSION: These results suggest that VEGF may have dual
      roles in ALI: early release of VEGF may increase pulmonary vascular permeability;
      reduced expression of VEGF and VEGFR-1 in lung tissue may contribute to the death
      of alveolar epithelial cells.

PMID- 16968556
TI  - Laparoscopic hysterectomy with or without pelvic lymphadenectomy or sampling in a
      high-risk series of patients with endometrial cancer.
AB  - BACKGROUND: The purpose of the study was to determine the outcome of all patients
      with endometrial adenocarcinoma cancer treated by laparoscopic hysterectomy at
      our institution, many of whom were high-risk for surgery. METHODS: Data was
      collected by a retrospective search of the case notes and Electronic Patient
      Records of the thirty eight patients who underwent laparoscopic hysterectomy for
      endometrial cancer at our institutions. RESULTS: The median body mass index was
      30 (range 19-67). Comorbidities were present in 76% (29 patients); 40% (15
      patients) had a single comorbid condition, whilst 18% (7 patients) had two, and a
      further 18% (7 patients) had more than two. Lymphadenectomy was performed in 45%
      (17 patients), and lymph node sampling in 21% (8 patients). Median operating time
      was 210 minutes (range 70-360 minutes). Median estimated blood loss was 200 ml
      (range 50-1000 ml). There were no intraoperative complications. Post-operative
      complications were seen in 21% (2 major, 6 minor). Blood transfusion was required
      in 5% (2 patients). The median stay was 4 post-operative nights (range 1-25
      nights). In those patients undergoing lymphadenectomy, the mean number of nodes
      taken was fifteen (range 8-26 nodes). The pathological staging was FIGO stage I
      76% (29 patients), stage II 8% (3 patients), stage III 16% (6 patients). The
      pathological grade was G1 31% (16 patients), G2 45% (17 patients), G3 24% (8
      patients). CONCLUSION: Laparoscopic hysterectomy can be safely carried out in
      patients at high risk for surgery, with no compromise in terms of outcomes,
      whilst providing all the benefits inherent in minimal access surgery.

PMID- 16968559
TI  - Dietitians' opinions and experiences of client-centred nutrition counselling.
AB  - PURPOSE: The concept of "client-centredness" was explored within a nutrition
      counselling relationship. METHODS: A two-round reactive Delphi survey was used.
      The first survey was sent to 65 Dietitians of Canada members who indicated in the
      member database that they had advanced counselling skills. Following analysis of
      the data, the second-round questionnaire was developed and sent to participants
      with a report of the first-round results. Analysis of the second-round survey
      indicated that participants' responses had remained stable, and the Delphi survey
      was terminated. RESULTS: Participants agreed that most of the issues identified
      in the Delphi questionnaire should be included in a client-centred approach to
      practice; however, when participants were asked about their experience in these
      areas, median responses and/ or the interquartile ranges changed, indicating some
      difficulty in implementing the client-centred approach. Comments also indicated
      that the reality of their workplaces did not allow participants to be as client
      centred as they thought they should be, and suggested that the concept of "client
      centredness" is not universally understood by dietitians. CONCLUSION: If a client
      centred approach to practice is truly important, we need to start a dialogue
      within the profession to gain a deeper understanding of what this means and how
      it can be implemented.

PMID- 16968560
TI  - Prevalence of overweight and obesity in school-aged children.
AB  - PURPOSE: Childhood obesity is a public health concern in Canada. Few published
      anthropometric data are available to indicate obesity prevalence in Canadian
      children. Obesity prevalence is reported for school-aged children in 11 London,
      Ontario, schools. METHODS: Data on body weight and height were obtained using
      standardized procedures. United States Centers for Disease Control and Prevention
      (CDC) body mass index (BMI)-for-age references and Cole's international BMI
      reference were used to classify the children's weight categories. RESULTS: The
      study included 1,570 pupils aged six to 13. The CDC BMI references categorized
      16.6% and 11.8% of children as overweight and obese, respectively. In comparison,
      when the Cole BMI reference and cut-off points were used, 17.5% and 7.6% of
      children were classified as overweight and obese, respectively. CONCLUSION:
      Overweight is prevalent in the study population. Public health interventions are
      warranted to curb the obesity epidemic in school-aged children.

PMID- 16968561
TI  - The iron status of Canadian adolescents and adults: current knowledge and
      practical implications.
AB  - OVERVIEW: Iron is an essential nutrient, playing a central role in oxygen
      transport and cellular energy metabolism. The importance of ensuring adequate
      bioavailable dietary iron stems from the severe consequences associated with iron
      deficiency (ID) and anemia, including reduced immune function and resistance to
      infection, developmental delays and irreversible cognitive deficits in young
      children, impaired physical work performance, and adverse pregnancy outcomes.
      SPECIFIC POPULATIONS: Poor dietary iron intake and ID exist in Canada,
      particularly in women of reproductive age. Data from the provincial nutrition
      surveys suggest that the prevalence of inadequate iron intakes (and low intakes
      of absorbable iron) among women under 50 years of age is over 10%, which may
      reflect poor iron status. Teenage girls are at risk for low iron stores because
      of the adolescent growth spurt and the onset of menstruation; those who are
      vegetarian are at even greater risk. CONCLUSIONS: The Canadian diet has changed
      so that grain products are now the main source of dietary iron for all age
      groups. The public must be educated to ensure the consumption of adequate
      quantities of bioavailable iron and enhancing factors such as vitamin C.
      Industry, government, and health professionals must work together to promote
      healthy eating patterns and the selection of appropriate foods.

PMID- 16968562
TI  - Prevalence of childhood obesity in northeastern Ontario: a cross-sectional study.
AB  - PURPOSE: In Canada, the incidence of childhood obesity has tripled within the
      past 20 years. The prevalence of obesity in the Timmins, Ontario, student
      population was studied to gain knowledge for program planning and resource
      allocation, and to compare Centers for Disease Control and Prevention (CDC)
      criteria with Cole's international criteria for childhood obesity. METHODS:
      Anthropometric measurements of 801 students were taken. Students were chosen from
      randomly selected schools for each grade. Data were analyzed according to age,
      gender, and ethnicity. Data were also compared with other studies. Intragroup
      comparisons were performed using hypothesis testing for significance with the z
      table and chi-square test. RESULTS: Overweight and obesity prevalence was 28%
      according to CDC criteria. No statistical difference was found between genders or
      among ethnic groups, or between this study and other Canadian studies. In
      comparison with the CDC criteria, Cole's international criteria indicated less
      obesity and increased overweight prevalence. These differences were not
      statistically significant. CONCLUSIONS: The findings suggest that in the northern
      Ontario community of Timmins, the prevalence of childhood obesity is of epidemic
      proportions. When the findings are shared with different agencies, this study
      will help the health unit to take necessary public health measures to curb the
      epidemic.

PMID- 16968563
TI  - A nutrition odyssey: knowledge discovery, translation, and outreach. 2006 Ryley
      Jeffs Memorial Lecture.
AB  - BACKGROUND: The 21st-century model of health research is founded on a broad base
      of multidisciplinary research that is expeditiously and effectively translated
      into evidence-based practice, education, policy, and advocacy. The key objective
      is to improve the health of populations. DIETITIANS' ROLES: Dietitians, whether
      they are working in clinical or public health nutrition or food science, have a
      vital role to play in this paradigm of health research. As dietitians' roles have
      evolved beyond the traditional ones into subspecialties including epidemiology,
      nutrigenomics, functional foods, nutraceuticals, toxicology, natural health
      products, and multidisciplinary research, the need for advanced training in
      subspecialty fields has become essential. OPPORTUNITIES: A dietetics background
      is an excellent foundation upon which to develop a research career in one of
      these new areas of nutrition. Opportunities for personnel awards and research
      funding targeted at nutrition clinician-scientists and other nutrition
      subspecialists have grown tremendously in recent years. CONCLUSION: The
      information in this paper is intended to inspire dietitians seeking advanced
      academic training in one of the new exciting avenues for a career in nutrition.
      These avenues will permit dietitians to contribute to knowledge discovery,
      translation, and outreach to improve the nutritional status and health of
      populations in Canada and globally.

PMID- 16968564
TI  - Cytochalasin D as the depressant of contraction for the optical monitoring of
      action potentials in isolated rat atrium.
AB  - We used cytochalasin D to reduce contraction-related optical signals by
      inhibiting muscle contraction for the optical monitoring of action potentials,
      using a voltage-sensitive dye in isolated rat atrium preparations. The
      suppression of contraction-related signals was so strong that we concluded that
      this chemical is suitable for this purpose.

PMID- 16968565
TI  - Dosing patterns, treatment costs, and frequency of physician visits in adults
      with cancer receiving erythropoietic agents in managed care organizations.
AB  - OBJECTIVE: To investigate the dosing patterns and treatment costs of
      erythropoietic agents in adult (>or= 18 years of age) cancer patients newly
      initiated on epoetin alfa (EPO) or darbepoetin alfa (DARB) in managed care
      organizations. METHODS: An analysis of US medical claims (30 million lives in
      over 35 health plans) in the period July 1, 2002-February 28, 2005 was conducted.
      Patients with >or= 1 cancer claim within 90 days prior to initiating EPO or DARB,
      and who received at least two doses of the same erythropoietic agent, were
      included in this analysis. Weighted average weekly dosing, cumulative treatment
      dose, associated drug cost, dosing frequency patterns, and the frequency of
      outpatient visits were evaluated. The EPO:DARB dose ratio, based on average
      cumulative treatment doses, was assessed. RESULTS: 5639 EPO and 2166 DARB
      patients met the inclusion and exclusion criteria. The EPO group was older (EPO
      59.1 years; DARB 57.6 years; p < 0.001) with a higher proportion of men (EPO
      38.1%; DARB 33.1%; p < 0.001). Variable dosing frequency was observed with
      similar treatment durations for the two groups (days: EPO 55.6; DARB 57.7; p =
      0.122). A dose ratio of 236:1 was observed (average cumulative dose: EPO 252 856
      U; DARB 1072 mcg). Average drug cost was significantly higher in the DARB group
      (drug cost: EPO 3077 dollars; DARB 4674 dollars; p < 0.001). The average number
      of hematology/oncology outpatient visits per patient (visits: EPO 7.4; DARB 7.3;
      p = 0.676) and outpatient visits for hemoglobin determination (visits: EPO 6.7;
      DARB 6.4; p = 0.093) during treatment was similar between the two groups.
      LIMITATIONS: The results were based on medical claims only. The absence of
      information on actual injection dates in pharmacy claims prevented their
      incorporation in the analysis. CONCLUSIONS: Based on the average cumulative
      doses, the EPO:DARB dose ratio was 236:1 (Units EPO: mcg DARB) with 52% greater
      drug cost in the DARB group. Despite the variable administration frequency
      observed between the two agents, the number of hematology/oncology outpatient
      visits was not different.

PMID- 16968566
TI  - A polysomnography study of eszopiclone in elderly patients with insomnia.
AB  - OBJECTIVE: To evaluate the safety and efficacy of eszopiclone 2 mg in elderly
      patients (aged 64-86 years) with chronic insomnia. METHODS: This was a
      randomized, double-blind, placebo-controlled 2-week study. Patients meeting DSM
      IV criteria for primary insomnia and screening polysomnography criteria
      (wakefulness after sleep onset [WASO] >or= 20 min and latency to persistent sleep
      >or= 20 min) were randomized to 2 weeks of nightly treatment with eszopiclone 2
      mg (n = 136) or placebo (n = 128). Efficacy was assessed using polysomnography
      (Nights 1, 2, 13, and 14) and patient reports (Nights 1-14); safety was assessed
      using adverse events, clinical labs, physical examination, and vital signs. The
      mean of all efficacy results during the double-blind period was used for the
      efficacy analysis. RESULTS: Results indicated that eszopiclone was associated
      with significantly shorter sleep onset, less WASO, higher sleep efficiency, more
      total sleep time, and greater patient-reported quality and depth of sleep scores
      than placebo (p < 0.05 for all) with a trend in patient-reported morning
      sleepiness (p = 0.07). Other measures of daytime functioning (ability to
      function, daytime alertness, and sense of well-being) were not significantly
      different between the two treatment groups. Among patients who napped,
      eszopiclone patients reported fewer naps (p = 0.03) and less cumulative naptime
      (median: 98 min placebo, 70 min eszopiclone, p = 0.07). Unpleasant taste, dry
      mouth, somnolence, and dizziness were higher in the eszopiclone group (12.5%,
      8.8%, 6.6%, and 6.6%, respectively) than in the placebo group (0%, 1.6%, 5.5%,
      and 1.6%, respectively). CONCLUSION: In this study, eszopiclone was well
      tolerated and produced significant improvements in both polysomnographic and
      patient-reported measures of sleep maintenance, sleep induction, and sleep
      duration in elderly patients with chronic primary insomnia.

PMID- 16968567
TI  - Ocular hypotensive efficacy and safety of brinzolamide ophthalmic suspension 1%
      added to travoprost ophthalmic solution 0.004% therapy in patients with open
      angle glaucoma or ocular hypertension.
AB  - OBJECTIVE: The primary objective of this study was to determine if combined
      travoprost ophthalmic solution 0.004% and brinzolamide ophthalmic suspension 1%
      therapy is superior in lowering intraocular pressure (IOP) compared to travoprost
      monotherapy for patients with open angle glaucoma or ocular hypertension. The
      secondary objective was to measure the percentage of patients achieving IOP
      levels of 18 mmHg or less. STUDY DESIGN AND METHODS: Single arm, open-label.
      PARTICIPANTS: eighty-two patients with inadequate IOP control with travoprost
      monotherapy. INTERVENTION: the addition of brinzolamide ophthalmic suspension 1%
      twice daily. MAIN OUTCOME MEASURES: The primary endpoint was mean IOP reduction
      from baseline at 4 and 12 weeks. The percentage of patients who achieved IOP
      values <or= 18 mmHg was also measured. RESULTS: The mean age of the patients was
      67 years. Ethnic origin was 92.7% Caucasian, 3.7% Black, 2.4% Asian and 1.2%
      other. The mean duration of travoprost treatment before the trial started was 30
      weeks. Compared to the baseline data (IOP = 22.5 mmHg) with travoprost ophthalmic
      solution 0.004% monotherapy, IOP was decreased after 4 (n = 78) and 12 (n = 71)
      weeks of combined travoprost and brinzolamide therapy by an average of 3.9 mmHg
      (17.4%) and 4.2 mmHg (18.4%), respectively. At baseline 6.3% of patients had an
      IOP of 18 mmHg or less whereas at 4 and 12 weeks, 53.8% and 60.6% of patients
      respectively had an IOP of 18 mmHg or less. Common adverse events were mild and
      included ocular hyperaemia, dysgeusia and eye irritation. STUDY LIMITATIONS: this
      study had a small sample size and was open-label. CONCLUSION: Patients receiving
      combined travoprost ophthalmic solution 0.004% and brinzolamide ophthalmic
      suspension 1% therapy had lower IOP values compared to those on travoprost
      monotherapy (p < 0.0001). Combined therapy resulted in a significantly greater
      percentage of patients achieving IOPs of 18 mmHg or less (p < 0.0001).

PMID- 16968568
TI  - Restoration of vestibular function: basic aspects and practical advances for
      rehabilitation.
AB  - BACKGROUND: Normal balanced functioning of the human vestibular system is
      required to achieve an upright stance and locomotion, head and eye stabilization
      and internal spatial representation; any lesion in this system will disrupt these
      functions. SCOPE: This review synthesizes previous work performed by the author
      and his research group in both animal models and vestibular defective patients
      over the last three decades. The author presents both an updated view on the
      basic mechanisms underlying the two main theories of vestibular compensation and
      his views on the principles that should guide management and rehabilitation of
      patients with vestibular loss. FINDINGS: Static deficits, following the loss or
      disruption of vestibular functions, are fully compensated; this is explained by
      the vestibulo-centric theory that suggests different plastic changes occurring in
      the vestibular nuclei complexes. In contrast, dynamic deficits remain poorly
      compensated; the restoration of dynamic vestibular functions results from
      substitution processes and vicarious strategies. The practical advances in the
      rehabilitation of vestibular defective patients are as follows: (1) perform
      rehabilitation at an early stage; (2) favour active retraining; (3) do not use
      stereotyped rehabilitation programs but adapt exercises to the patients; (4)
      examine patients in standardized environments; (5) use both static and dynamic
      tests; and (6) avoid drugs with sedative effects (or limit them to the very acute
      stage only) and prescribe those accelerating the recovery process (e.g.
      betahistine dihydrochloride). CONCLUSION: Recovery of vestibular function is
      greatest when early active retraining and adequate pharmacological treatments are
      used in combination.

PMID- 16968569
TI  - Comparison of gastro-oesophageal reflux disease and heartburn diagnoses in UK
      primary care.
AB  - OBJECTIVE: It is unclear how gastro-oesophageal reflux disease (GORD) is
      diagnosed in primary care. The aim of this study is to compare patients given a
      diagnosis of GORD with those diagnosed with heartburn. RESEARCH DESIGN AND
      METHODS: Data from the UK General Practice Research Database were extracted for
      patients newly diagnosed with heartburn (n = 1841) or GORD (n = 5318) in 1996.
      MAIN OUTCOME MEASURES: Patient characteristics, morbidity, healthcare use and
      prescribed treatments were compared using unconditional logistic regression
      analysis. RESULTS: GORD was diagnosed more frequently than heartburn (3.2 vs. 1.1
      per 1000 patient-years). A diagnosis of GORD was less likely among females (odds
      ratio (OR): 0.8; confidence interval (CI): 0.7-0.9), smokers (OR: 0.8; CI: 0.7
      0.9) and patients who consulted their physician frequently (OR: 0.8; CI: 0.7
      0.9). There was a wide distribution in the ratio of GORD-to-heartburn diagnoses
      between primary care practices (mean 2.9; range 0-infinity). GORD patients were
      more likely to receive proton pump inhibitors (OR: 2.9; CI: 2.6-3.4), but 24% of
      GORD patients and 40% of heartburn patients received no acid-suppressive
      treatment in the month after diagnosis. CONCLUSIONS: Several factors influenced
      the diagnosis of gastro-oesophageal reflux symptoms by primary care physicians.
      Further research is needed to aid the diagnosis of GORD in primary care.

PMID- 16968570
TI  - A phase I trial of an interleukin-12/23 monoclonal antibody in relapsing multiple
      sclerosis.
AB  - OBJECTIVE: To assess the safety, tolerability and pharmacokinetics of an
      interleukin (IL)-12/23 monoclonal antibody (mAb) in subjects with a relapsing
      form of multiple sclerosis (MS). METHODS: A phase I, double-blind, placebo
      controlled, sequential dose escalation study was conducted in 20 subjects with
      MS. Subjects were randomized (4:1) to receive a single subcutaneous injection of
      either IL-12/23 mAb (0.3, 0.75, 1.5, and 3.0 mg/kg) or placebo. Clinical and
      laboratory evaluations were performed through 16 weeks following administration.
      RESULTS: IL-12/23 mAb was well tolerated in this study. Adverse events were
      generally mild or moderate, with no apparent dose-related trends. One subject
      with a family history of breast cancer was diagnosed during the study with breast
      cancer 21 days after IL-12/23 mAb administration. There were no significant
      changes in laboratory indicators of systemic or neurotoxicity. There was a large
      degree of variability in T2 lesion volume and total number of gadolinium-positive
      lesions, both unaffected by dose escalation. Three relapses of MS occurred in two
      placebo-treated subjects. Over the range of single doses studied, the median Tmax
      ranged from 9.0 to 16.5 days, and the median T1/2 ranged from 20.2 to 30.9 days.
      CONCLUSION: Single subcutaneous administrations of IL-12/23 mAb in this first
      study of relapsing MS were generally well tolerated. Safety of the agent will
      need to be tested in a study of longer duration and involving a larger cohort of
      subjects.

PMID- 16968571
TI  - Development of a COPD severity score.
AB  - OBJECTIVE: Treatment of chronic obstructive pulmonary disease (COPD) is based on
      symptom control. This suggests that COPD severity can be determined by analyzing
      treatment intensity. The objective of this analysis was to develop and validate a
      severity score for adult COPD based on treatments. RESEARCH DESIGN: Using
      principal components analysis, a COPD severity score was developed using data
      based on treatments extracted from an employer claims database (development
      group). Variables included were identified from literature review and clinical
      expert opinion. External validity was tested in a separate group of adult chronic
      bronchitis patients in whom principal components analysis was re-conducted and
      factor loadings were compared to the development group. Construct validity was
      tested by comparing the incidence of acute exacerbations of chronic bronchitis
      (AECB) in patients with high and lower severity scores. To illustrate the use of
      the COPD severity score, effectiveness of alternative AECB antibiotic treatments
      was compared in a separate patient sample categorized by severe versus
      mild/moderate COPD. RESULTS: In the development group (n = 2068), principal
      components analysis produced a single main factor for severity scoring. Of the 12
      variables contributing to this factor, the 6 with the highest factor loadings
      were treatment related. The factor performed similarly in the external validity
      group (n = 9127) as it did in the development group. In construct validity
      testing, severe COPD patients were 4 times more likely to have AECB episodes than
      mild/moderate patients. Patients with severe COPD and an AECB were more likely to
      fail treatment with antibiotics than those with mild/moderate COPD. Based on the
      COPD severity score developed, we found that treatment of patients with severe
      COPD and an AECB with fluoroquinolones was more likely to result in treatment
      failure than treatment with macrolides (OR = 2.01; p = 0.03). CONCLUSIONS: The
      analysis was successful in developing and validating a method to score COPD
      severity based on treatments. This method may prove useful in providing insights
      about the benefits of COPD treatments.

PMID- 16968572
TI  - Circadian IOP-lowering efficacy of travoprost 0.004% ophthalmic solution compared
      to latanoprost 0.005%.
AB  - PURPOSE: The primary objective of this study was to determine the intraocular
      pressure- (IOP) lowering efficacy over two consecutive 24-h periods of travoprost
      0.004% ophthalmic solution (Travatan) compared to latanoprost 0.005% (Xalatan)
      dosed once daily in patients with primary open-angle glaucoma or ocular
      hypertension. METHODS: This was a double-masked trial conducted at the Hospital
      Clinico San Carlos, Madrid, Spain. The primary objective of this study was to
      determine the IOP lowering efficacy of travoprost and latanoprost. During the
      eligibility visit, patients' IOP was measured throughout two consecutive 24-h
      periods every 4 h. Patients were then randomized to travoprost or latanoprost
      (one drop at 8 p.m. daily for 2 weeks). Sixty-two patients were randomized
      (travoprost n = 32; latanoprost n = 30). IOP was measured at week 2 every 4 h
      throughout two 24-h periods. All measurements were taken in both supine and
      sitting positions with the aid of Perkins applanation tonometry. Limitations of
      the study include a small sample size (due to the difficulty in recruiting
      patients in a study of this type) which enrolled only Caucasian patients and a
      short study duration. However, with 25 subjects per group, there was at least 90%
      power to detect a mean IOP change from baseline of 2.9 mmHg and 80% power to
      detect a difference of 2.5 mmHg between treatments. RESULTS: Patients on
      travoprost therapy showed lower mean IOP levels than those on latanoprost. This
      difference was statistically significant (p < 0.05) at 12, 16, 20, 24, 36, 40,
      and 48 h after the last dose for the supine position. The mean IOPs in the supine
      position throughout the first and the second 24-h period of the week 2 visit as
      well as for the 48-h visit were statistically lower (p < 0.05) for the travoprost
      group. Adverse events were mild and included hyperemia and corneal staining.
      Travoprost and latanoprost were both well tolerated. CONCLUSION: Mean IOP values
      were significantly lower for patients on travoprost for the majority of time
      points in the supine position.

PMID- 16968573
TI  - Single-dose famciclovir for the treatment of herpes labialis.
AB  - BACKGROUND: Approximately 20% to 40% of the population experience recurrent
      herpes labialis caused by herpes simplex virus type 1 (HSV-1). Since there is no
      cure, patients typically use antiviral therapy to treat outbreaks as they occur.
      A large proportion of patients self-administer topical antiviral therapies at the
      onset of symptoms, but lack of efficacy, frequent dosing, and inconvenient long
      term treatment regimens have made the use of oral antiviral therapies more
      common. Valacyclovir is currently the only oral antiviral approved for the
      treatment of herpes labialis in immunocompetent individuals. The
      pharmacokinetic/pharmacodynamic profile of famciclovir suggests that it could be
      utilized for episodic treatment for immunocompetent individuals as well.
      FINDINGS: A recent study comparing single-dose vs. single-day bid famciclovir and
      placebo in the treatment of herpes labialis demonstrated single-dose famciclovir
      to be as efficacious as single-day bid dosing in time to healing of lesions and
      more efficacious than single-day bid famciclovir in time to resolution of pain
      and tenderness. Both were statistically superior to placebo. When results of this
      study were compared with recently published results of other frequently
      prescribed treatments, single-dose famciclovir appeared to produce similar or
      better improvements in healing time and duration of pain. CONCLUSIONS: Single
      dose famciclovir appears to be an effective, convenient therapy for recurrent
      herpes labialis. The convenience of single-dose therapy may lead to better
      overall management of the condition.

PMID- 16968574
TI  - A comparative, randomized, double-blind study of trazodone prolonged-release and
      sertraline in the treatment of major depressive disorder.
AB  - OBJECTIVES: To evaluate the efficacy and safety of trazodone prolonged-release
      compared with sertraline in the treatment of patients with major depression.
      RESEARCH DESIGN AND METHODS: A total of 122 patients aged 19-64 years were
      enrolled in this multicenter, double-blind, double-dummy, randomized, comparator
      controlled study. Patients received 7 days of single-blind placebo treatment
      followed by 6 weeks of double-blind treatment with trazodone prolonged-release
      150-450 mg/day (n = 62) or sertraline 50-100 mg/day (n = 60). OUTCOME MEASURES:
      Efficacy was evaluated by mean changes from baseline in the Hamilton Depression
      Rating scale (HAM-D), Montgomery Asberg Depression Rating Scale, Hamilton Anxiety
      Rating scale, and the Clinical Global Impression-Global Improvement/Severity
      scores; and by the rates of patients responding to treatment and considered to be
      in remission. Time to onset of efficacy and safety were assessed. RESULTS:
      Trazodone and sertraline were equally effective in reducing depressive symptoms
      and promoting remission, and had similar onset times. In the Intent-to-Treat
      population, there were no significant differences in favor of trazodone at study
      endpoint in all efficacy measures, while a statistically significant difference
      was detected in the Per-Protocol population on HAM-D and in the percentage of
      responders. Analysis of HAM-D factors (anxiety/somatization, cognitive
      disturbance, retardation, and sleep disturbance) indicated that sleep
      disturbances were significantly less evident for patients taking trazodone at
      study endpoint. Adverse drug reactions, mostly of mild intensity, were reported
      in 42% of trazodone-treated patients (mainly of the nervous system) and 43% of
      sertraline-treated patients (mainly gastrointestinal). One event was considered
      to be serious: a patient treated with trazodone 450 mg/day showed moderate
      anxiety/tremor/insomnia and was hospitalized. Treatment was discontinued; the
      patient made a full recovery. CONCLUSIONS: This study showed that after 6 weeks,
      trazodone and sertraline were not different in reducing symptoms of depression
      and in producing disease remission. Tolerability profiles reflected the differing
      pharmacological properties of these antidepressants. Trazodone may be a
      therapeutic option in the treatment of patients with major depression showing
      prevalent sleep disturbances.

PMID- 16968575
TI  - Reductions in biomarkers of cardiovascular risk in type 2 diabetes with
      rosiglitazone added to metformin compared with dose escalation of metformin: an
      EMPIRE trial sub-study.
AB  - OBJECTIVE: To compare the effects of rosiglitazone added to metformin with dose
      escalation of metformin on cardiovascular risk biomarkers in type 2 diabetes
      mellitus. RESEARCH DESIGN AND METHODS: Cardiovascular biomarkers were assessed in
      a sub-population of 122 subjects with type 2 diabetes mellitus (mean age 54.6 and
      56.0 years, BMI 34.7 and 32.1 kg/m2; for the rosiglitazone plus metformin and
      metformin groups, respectively) from the multicenter (63 centers in the USA),
      double-blind, randomized parallel-group Escalation of Metformin theraPy vs.
      Initiation of Rosiglitazone Early (EMPIRE) study. Treatment group sizes were
      slightly imbalanced owing to central, rather than local, randomization. Subjects
      receiving metformin 1000 mg/day at baseline were randomized to rosiglitazone 4
      mg/day plus metformin 1000 mg/day (RSG + MET) or metformin 1500 mg/day (up
      titrated MET) for 24 weeks. At 8-weeks, rosiglitazone was increased to 8 mg/day
      in RSG + MET recipients and metformin to 2000 mg/day in up-titrated MET
      recipients. RESULTS: Reductions from baseline in HbA1c at week 24 (mean +/- SD)
      occurred in both groups (RSG + MET: -0.61% +/- 1.16%; up-titrated MET: -0.65% +/-
      1.18%). Post-prandial glucose levels (AUC(0-3h)) decreased with RSG + MET (-3.5
      mmol/L.h; 95% confidence interval [CI]: -5.2 to -1.8) and up-titrated MET (-1.3
      mmol/L.h; 95% CI: -3.8 to 1.1). Homeostasis Model Assessment (HOMA)-estimated
      insulin sensitivity increased by 37.7% (95% CI: 22.8 to 54.5) in RSG + MET and
      6.9% (95% CI: -6.2 to 21.9) in up-titrated MET recipients. RSG + MET reduced C
      reactive protein (CRP; -23.9%; 95% CI: -40.4 to -2.8), plasminogen activator
      inhibitor-1 (PAI-1) activity (-30.1%; 95% CI: -44.5 to -11.9), PAI-1 antigen (
      15.5%; 95% CI: -28.3 to -0.3) and matrix metalloproteinase-9 (MMP-9; -13.8%; 95%
      CI: -25.1 to -0.9), but increased tumor necrosis factor-alpha (TNF-alpha; 27.0%;
      95% CI: 6.8 to 50.9). Corresponding values for up-titrated MET were CRP -9.3%
      (95% CI: -36.9 to 30.2), PAI-1 activity -7.2% (95% CI: -28.2 to 20.0), PAI-1
      antigen -1.5% (95% CI: -17.4 to 17.5), MMP-9 29.0% (95% CI: -1.3 to 68.6) and TNF
      alpha -6.0% (95% CI: -22.0 to 13.2). CONCLUSIONS: These results suggest that
      rosiglitazone plus metformin has positive cardiovascular effects against a
      background of similar glycemic improvements.

PMID- 16968576
TI  - Once-daily ofloxacin otic solution versus neomycin sulfate/polymyxin B
      sulfate/hydrocortisone otic suspension four times a day: a multicenter,
      randomized, evaluator-blinded trial to compare the efficacy, safety, and pain
      relief in pediatric patients with otitis externa.
AB  - INTRODUCTION: Otitis externa (OE) is an infection of the external auditory canal
      affecting children and adults and is associated with symptoms of local pain and
      tenderness. Twice-daily topical treatment with ofloxacin otic solution (0.3%
      [Floxin otic solution]) for 10 days has been reported to be as effective and well
      tolerated as neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension
      (Cortisporin otic suspension) administered four times daily for 10 days.
      OBJECTIVE: This study compared the efficacy, safety, and ear-pain resolution of
      once-daily ofloxacin otic solution (0.3%) versus neomycin sulfate/polymyxin B
      sulfate/hydrocortisone otic suspension administered four times daily, in children
      with OE. RESEARCH DESIGN, PATIENTS, AND METHODS: This multicenter, randomized,
      parallel-group, evaluator-blinded study was conducted at 34 centers in 278
      pediatric OE patients aged 6 months to 12 years. Patients received five drops of
      ofloxacin otic solution (0.3%) in the affected ears once daily or three drops of
      neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension four times
      daily, for 7-10 days. Patient evaluations were performed at pretherapy (day 1),
      end of therapy (days 7-9), and test of cure (7-10 days post-treatment) visits.
      Data for 208 patients were clinically evaluable and those for 90 patients were
      microbiologically evaluable. Scores were obtained for patient assessments of pain
      severity. MAIN OUTCOME MEASURES: The overall clinical response was cure in the
      clinically evaluable patients, demonstrated by resolution of OE signs and
      symptoms at the test of cure visit. The overall clinical-microbiological response
      was cure in the microbiologically evaluable patients demonstrated by both
      clinical cure and microbiological eradication. RESULTS: For the clinically
      evaluable patients, equivalent cure rates were obtained between the once-daily
      ofloxacin-treated and four-times-daily neomycin sulfate/polymyxin B
      sulfate/hydrocortisone-treated patients (93.8% and 94.7%, respectively). For the
      clinically and microbiologically evaluable patients, the overall cure rates were
      96.4% versus 97.1% for the ofloxacin-treated and neomycin sulfate/polymyxin B
      sulfate/hydrocortisone-treated patients, respectively. The eradication rates for
      the prevalent pathogen, Pseudomonas aeruginosa, were 98% versus 100% for
      ofloxacin-treated and neomycin sulfate/polymyxin B sulfate/hydrocortisone-treated
      patients, respectively. Decreases in pain severity were similar in both treatment
      groups. Statistical analyses were limited by the small numbers of patients in
      each treatment group. CONCLUSION: In the treatment of OE in children, once-daily
      ofloxacin otic solution was as effective and safe as neomycin sulfate/polymyxin B
      sulfate/hydrocortisone otic suspension given four times daily. The two treatments
      provide rapid and comparable pain relief; however, ofloxacin otic solution does
      not have the risk of ototoxicity associated with neomycin and provides effective
      pain relief without adjunctive steroids.

PMID- 16968577
TI  - Travoprost versus latanoprost combinations in glaucoma: economic evaluation based
      on visual field deficit progression.
AB  - OBJECTIVE: Changes in intraocular pressure (IOP) are known to be related to
      visual field deficit progression, although multiple models of this relationship
      exist. In addition, visual functioning is known to affect medical costs. The
      objective of this study was to project visual field deficit progression and
      subsequent costs based on clinical trial data. RESEARCH DESIGN AND METHODS: Using
      data from a randomized, 12-month, double-masked study, we compared the use of a
      fixed combination of travoprost 0.004%/timolol 0.5% (T/T) versus a fixed
      combination of latanoprost 0.005%/timolol 0.5% (L/T) on visual field deficit
      progression and associated costs. We applied published algorithms linking IOP to
      visual field changes to calculate the likelihood of visual field deterioration by
      treatment group. Differences in medical care costs were estimated using guideline
      recommended practice patterns, Medicare hospital costs, and published estimates
      of differences in hospitalization by visual functioning. MAIN OUTCOME MEASURES:
      Increase in visual field deficit progression rates, increase in annual hospital
      days per subject, and increase in annual hospital, outpatient, and total costs
      per subject. RESULTS: Predicted visual field deficit progression for T/T patients
      was less than that for L/T patients (not statistically significant). Projected
      annual medical care costs were 43 dollars lower for T/T vs. L/T patients.
      CONCLUSIONS: By applying published algorithms linking IOP to visual field
      changes, this study projected long-term visual field deficit and associated
      costs. Use of a fixed travoprost/timolol solution may lead to less long-term
      visual field deficit progression and lower annual medical care costs than a fixed
      latanoprost/timolol solution. DISCUSSION: The use of clinical trial data may
      limit the applicability of these findings. However, this analysis of direct
      medical costs only is likely a conservative estimate of the costs associated with
      visual field deficits.

PMID- 16968578
TI  - Alendronate with and without cholecalciferol for osteoporosis: results of a 15
      week randomized controlled trial.
AB  - OBJECTIVE: Many osteoporosis patients have low 25-hydroxyvitamin D (25OHD) and do
      not take recommended vitamin D amounts. A single tablet containing both
      cholecalciferol (vitamin D3) and alendronate would improve vitamin D status
      concurrently, with a drug shown to reduce fracture risk. This study assessed the
      efficacy, safety, and tolerability of a once-weekly tablet containing alendronate
      70 mg and cholecalciferol 70 microg (2800 IU) (ALN + D) versus alendronate 70 mg
      alone (ALN). METHODS: This 15-week, randomized, double-blind, multi-center,
      active-controlled study was conducted during a season when 25OHD levels are
      declining, and patients were required to avoid sunlight and vitamin D supplements
      for the duration of the study. Men (n = 35) and postmenopausal women (n = 682)
      with osteoporosis and 25OHD >or= 9 ng/mL were randomized to ALN + D (n = 360) or
      ALN (n = 357). MAIN OUTCOME MEASURES: Serum 25OHD, parathyroid hormone, bone
      specific alkaline phosphatase (BSAP), and urinary N-telopeptide collagen cross
      links (NTX). RESULTS: Serum 25OHD declined from 22.2 to 18.6 ng/mL with ALN
      (adjusted mean change = -3.4; 95% confidence interval [CI]: -4.0 to -2.8), and
      increased from 22.1 to 23.1 ng/mL with ALN + D (adjusted mean change = 1.2; 95%
      CI: 0.6 to 1.8). At 15 weeks, adjusted mean 25OHD was 26% higher (p < 0.001, ALN
      + D versus ALN), the adjusted relative risk (RR) of 25OHD < 15 ng/mL (primary
      endpoint) was reduced by 64% (incidence 11% vs. 32%; RR = 0.36; 95% CI: 0.27 to
      0.48 [p < 0.001]), and the RR of 25OHD < 9 ng/mL (a secondary endpoint) was
      reduced by 91% (1% vs. 13%; RR = 0.09; 95% CI: 0.03 to 0.23 [p < 0.001]).
      Antiresorptive efficacy was unaltered, as measured by reduction in bone turnover
      (BSAP and NTX). CONCLUSION: In osteoporosis patients who avoided sunlight and
      vitamin D supplements, this once-weekly tablet containing alendronate and
      cholecalciferol provided equivalent antiresorptive efficacy, reduced the risk of
      low serum 25OHD, improved vitamin D status over 15 weeks, and was not associated
      with hypercalcemia, hypercalciuria or other adverse findings, versus alendronate
      alone.

PMID- 16968579
TI  - Persistent bisphosphonate use and the risk of osteoporotic fractures in clinical
      practice: a database analysis study.
AB  - INTRODUCTION: International guidelines on the treatment and prevention of
      osteoporosis recommend the use of bisphosphonates to prevent fractures in this
      population. However, low persistent use of bisphosphonates could considerably
      limit the prevention of fractures in clinical practice. OBJECTIVE: This study
      aimed to investigate the association between persistent use of bisphosphonates
      and the risk of osteoporotic fractures in clinical practice. METHODS: Data were
      obtained from the PHARMO Record Linkage System, which includes, among other
      databases, drug-dispensing records from community pharmacies linked to hospital
      discharge records of more than two million subjects in defined areas in the
      Netherlands. Persistence with bisphosphonate therapy was assessed during a period
      of 3 years. A nested matched case control study (cases:controls = 1:10) was
      performed to study the association between persistent bisphosphonate use and
      hospitalisation for osteoporotic fractures and analysed by conditional logistic
      regression analysis. The analyses were adjusted for patient characteristics such
      as previous hospitalisations for fractures, co-morbidity and co-medication.
      RESULTS: 14,760 new female users of bisphosphonates were identified of which 541
      women had a hospitalisation for osteoporotic fracture after start of
      bisphosphonate treatment (1-3 years follow-up). One-year persistence rates
      increased from 33% with alendronate daily to 48% with alendronate weekly, an
      increase of 15%. Similar results were obtained with risedronate daily and weekly.
      One year persistent use of bisphosphonates resulted in a statistical significant
      26% lower fracture rate (OR 0.74; 95%CI 0.57-0.95) whereas 2 year persistent use
      resulted in a 32% lower rate (OR 0.68; 95%CI 0.47-0.96). CONCLUSIONS: Persistent
      use of bisphosphonates decreases the risk of osteoporotic fractures in clinical
      practice. Approximately 6% of fractures among users of bisphosphonates could be
      prevented if persistence was improved by 20%. However, current persistence with
      bisphosphonate therapy is suboptimal and strategies that further increase
      persistence are likely to further prevent the number of fractures.

PMID- 16968580
TI  - The economic value of anti-IgE in severe persistent, IgE-mediated (allergic)
      asthma patients: adaptation of INNOVATE to Sweden.
AB  - BACKGROUND: Severe allergic asthma patients may not be controlled even with
      guideline recommended care, including inhaled corticosteroids, long-acting beta-2
      agonists, theophylline, oral steroids and anti-leukotrienes. They experience
      exacerbations requiring intensive healthcare use and which may be fatal.
      Omalizumab, a new monoclonal antibody for use in IgE-mediated allergic diseases,
      reduces exacerbations and daily symptoms in this patient population. The aim of
      this study is to estimate the cost effectiveness of adding omalizumab to
      optimized standard therapy (ST) in patients with severe persistent IgE-mediated
      (allergic) asthma. METHODS: A Markov model comparing lifelong ST with a treatment
      period of omalizumab add-on therapy followed by ST, was developed based on
      efficacy data from the INNOVATE trial (28 weeks, N = 419) and Swedish life table
      and cost data. This model assumes that patients are at risk of having an
      exacerbation every 2 weeks and are at risk of dying from a clinically significant
      severe asthma exacerbation. Patients in a steady-state of having no exacerbations
      are defined to be in an 'optimized asthma control' state. Resource use data and
      utilities were obtained from INNOVATE and from a UK observational study. Costs
      from a societal perspective include estimates for drugs, routine care,
      exacerbations and costs in added years of life; benefits are expressed in QALYs.
      The response to omalizumab was evaluated after 16 weeks of trial, and non
      responders stopped taking omalizumab for the remaining time. RESULTS: Total
      lifetime discounted costs and QALYs on ST were 52,702 euros and 11.60. Omalizumab
      add-on therapy cost an additional 42,754 euros for 0.76 additional QALYs,
      resulting in an incremental cost-effectiveness ratio of 56,091 euros. A
      probabilistic sensitivity analysis indicates that the 95% CI around the ICER is
      [31,328 euros; 120,552 euros]. One-way analyses indicate that the results are
      sensitive to the exacerbation-related mortality rate, the time horizon and the
      discount rates. CONCLUSIONS: Based on the model and the assumptions used, our
      results suggest that omalizumab provides cost offsets, improves quality of life
      and may have an attractive ICER in treating the severe allergic asthma
      population.

PMID- 16968581
TI  - Health economic impact of olopatadine compared to branded and generic sodium
      cromoglycate in the treatment of seasonal allergic conjunctivitis in the UK.
AB  - OBJECTIVE: This study estimated the health economic impact of olopatadine
      (Opatanol) compared to branded cromoglycate (Opticrom) and generic sodium
      cromoglycate in the treatment of seasonal allergic conjunctivitis (SAC) in the
      UK. DESIGN AND SETTING: This was a modelling study performed from the perspective
      of the UK's National Health Service (NHS). METHODS: A decision model was
      constructed depicting the management of SAC sufferers who are 4 years of age or
      above over a typical allergy season of 4 months and considers the decision by a
      GP to initially treat a patient with olopatadine, branded or generic
      cromoglycate. The analysis assumed both drugs to be equally effective.
      Consequently, a cost-minimisation analysis was performed to identify the least
      costly alternative. MAIN OUTCOME MEASURES AND RESULTS: Starting treatment with
      olopatadine is expected to lead to a healthcare cost of 92 pounds sterling (95%
      CI: 46 pounds sterling; 150 pounds sterling) over 4 months compared to 109 pounds
      sterling (95% CI: 65 pounds sterling; 166 pounds sterling) with branded
      cromoglycate and 95 pounds sterling (95% CI: 51 pounds sterling; 152 pounds
      sterling) with generic cromoglycate, resulting in a 16% and 3% reduction in
      healthcare costs respectively over 4 months of treatment. This cost-difference is
      primarily due to fewer GP visits among olopatadine-treated patients. CONCLUSION:
      Use of olopatadine instead of branded or generic cromoglycate affords an economic
      benefit to the NHS. Hence, within the limitations of the model, olopatadine is
      the preferred first-line treatment for use in SAC sufferers, since it is expected
      to lead to fewer GP visits, thereby releasing healthcare resources for
      alternative use.

PMID- 16968582
TI  - Health-related quality of life burden of women with endometriosis: a literature
      review.
AB  - PURPOSE: The purpose of this study was to conduct a comprehensive and systematic
      literature review of the health-related quality of life (HRQL) burden of
      endometriosis in adults and adolescents. METHODS: We conducted a systematic
      search and review of studies published between January 1999 and January 2006
      using MEDLINE and relevant online resources. Search terms used included
      endometriosis, quality of life, burden of illness, psychology, and adolescent. We
      assessed: (1) the HRQL impact of endometriosis and related key symptoms; (2) the
      impact of specific pharmacologic and surgical treatments of endometriosis on
      HRQL; and (3) the presence and impact of endometriosis in adolescents. RESULTS:
      Twenty relevant studies were identified and reviewed. Generic instruments most
      commonly used to assess HRQL in patients with endometriosis included the SF-36
      and the SF-12. The EQ-5D was used to measure utilities. The Endometriosis Health
      Profile-30 (EHP-30) and its subset, the EHP-5, have been recently developed for
      use in endometriosis studies. Endometriosis was associated with significant
      impairments in pain, psychological functioning, and social functioning.
      Pharmacological and surgical treatments for endometriosis improved patients
      physical functioning, psychological functioning, vitality, pain level, and
      general health. Few studies used disease specific instruments to characterize the
      HRQL burden of endometriosis, addressed the HRQL impact of endometriosis-related
      infertility, and examined endometriosis in adolescents. Instruments specifically
      validated to measure HRQL in adolescents were not identified. CONCLUSIONS:
      Endometriosis impairs HRQL, especially in the domains of pain, psychological and
      social functioning. Therapies have been shown to alleviate symptoms and improve
      HRQL. Further research is warranted to evaluate the impact of endometriosis on
      HRQL in adolescents and the impact of infertility due to endometriosis on HRQL.

PMID- 16968583
TI  - Comparison of the efficacy and safety of travoprost with a fixed-combination of
      dorzolamide and timolol in patients with open-angle glaucoma or ocular
      hypertension.
AB  - PURPOSE: The purpose of this study was to compare travoprost (TRAV; travoprost
      0.004%) and the fixed-combination of dorzolamide/timolol (DTFC; dorzolamide
      2.0%/timolol maleate 0.5%) ophthalmic solutions for reducing intraocular pressure
      (IOP) in patients with primary open-angle glaucoma (OAG) or ocular hypertension
      (OHT). METHODS: This was a randomized single masked, study with parallel
      controls. The TRAV group (n = 29) dosed once daily at 9:00 PM while the DTFC
      group (n = 27) dosed twice daily at 9:00 AM and 9:00 PM. IOP was measured at
      baseline, and following 3 weeks and 6 weeks of treatment at 8:00 AM, 12:00 PM,
      4:00 PM, and 8:00 PM. RESULTS: Mean average IOP reductions from baseline during
      the course of the day were 7.5 (32.7%) and 7.1 (30.7%) mmHg for TRAV and 4.8
      (23.1%) and 4.5 (21.7%) mmHg for DTFC at 3 weeks and 6 weeks, respectively. The
      greater IOP reduction for patients receiving TRAV was statistically significant
      at both the 3 and 6 week visits when averaged across all four time points (p <
      0.01). The two products were well-tolerated over the course of the 6 week study.
      Some factors such as taste perversion were reported more often in the DTFC group.
      CONCLUSIONS: Travoprost monotherapy provided better efficacy in terms of IOP
      reduction and percentage of IOP reduction compared to dorzolamide 2.0%/timolol
      maleate 0.5% fixed combination.

PMID- 16968584
TI  - Conflict of interest or ideological divide: the need for ongoing collaboration
      between physicians and industry.
AB  - Continued collaboration between the health profession and industry is essential
      for future innovation and for fighting disease and illness well into the 21st
      century. Evidence that suggests conflicts of interest have a negative effect on
      patient care or the total cost of health care is lacking. Many arguments put
      forth to address this issue include strictly limiting or severing ties with
      industry. Research takes place in university, government, and pharmaceutical
      laboratories, but only industry translates research into drug therapy. While both
      parties have a shared goal of optimizing health outcomes, industry critics
      conveniently invoke 'conflict of interest' to express their opinion about the
      need to more strictly regulate physician/industry interactions. Retreat from
      industry by academic institutions and working in isolation are simply not
      strategic options and other points of view must be expressed to help avoid the
      'triumph of emotion over fact'.

PMID- 16968585
TI  - Safety, tolerability and pharmacokinetics of escalating doses of NXY-059 in
      healthy young and elderly subjects.
AB  - OBJECTIVE: NXY-059 is a novel, free-radical trapping, neuroprotectant that
      reduces infarct size and preserves brain function in animal models of acute
      ischaemic stroke. This study evaluated the safety, tolerability and
      pharmacokinetics of NXY-059 in the unbound steady-state plasma concentration
      (Cu(ss)) exposure range of 50-300 micromol/L in healthy young and elderly
      subjects. RESEARCH DESIGN AND METHODS: The primary objective of this two-centre,
      randomised, double-blind, placebo-controlled, dose-escalating study was to
      investigate the safety and tolerability, including renal function parameters and
      vasoirritative effects, of 8-h and 72-h intravenous infusions of NXY-059 in
      healthy young (20-45 years) and elderly (55-75 years) male and female subjects.
      The secondary objective of the study was to evaluate the pharmacokinetics of 8-h
      and 72-h intravenous infusions of NXY-059 in these subjects, using blood and
      urine samples taken during and after NXY-059 infusion as well as the doses
      administered. RESULTS: Of the 104 healthy volunteers who participated in the
      study, 72 were young and 32 were elderly. The type and incidence of adverse
      events in NXY-059 and placebo subjects were similar, although headache was more
      common in the NXY-059 group. Renal function was not altered in either group.
      Thrombophlebitis was reported in two elderly subjects: one receiving NXY-059 and
      one receiving placebo. A proportional relationship between AUC and dose for the 8
      h and 72-h infusions was observed, and clearance did not change with dose.
      CONCLUSIONS: NXY-059 was well tolerated at all plasma concentrations tested in
      both the young and elderly subjects, and no safety concerns were raised. Linear
      pharmacokinetics were observed following 8-h and 72-h infusions of NXY-059 at
      doses resulting in an average Cu(ss) in the 52-317 micromol/L range.

PMID- 16968586
TI  - Remission, dropouts, and adverse drug reaction rates in major depressive
      disorder: a meta-analysis of head-to-head trials.
AB  - OBJECTIVE: To summarize remission rates and dropouts due to adverse drug
      reactions (ADRs) or lack of efficacy (LoE) of serotonin-norepinephrine reuptake
      inhibitors (SNRIs), selective serotonin-reuptake inhibitors (SSRIs), and
      tricyclic antidepressants (TCAs) in treating major depressive disorder. METHODS:
      We searched MEDLINE, EMBASE, IPA, and the Cochrane International Library from
      1980-2005. Meta-analysis summarized outcomes from head-to-head randomized
      clinical trials comparing >or= 2 drugs from three antidepressants classes (SNRIs,
      and/or SSRIs, and/or TCAs) followed by >or= 6 weeks of treatment. Remission was a
      final Hamilton Depression Rating Scale (HAMD) score <or= 7 or Montgomery-Asberg
      Depression Rating Scale (MADRS) <or= 12. Intent-to-treat data were combined
      across study arms using random effects models, producing point estimates with 95%
      confidence intervals. RESULTS: We obtained data from 30 arms of 15 head-to-head
      trials with 2458 patients. SNRIs had the highest ITT remission rate (49.0%), then
      TCAs (44.1%), and SSRIs (37.7%) (p > 0.05 for SNRIs versus TCAs; p < 0.001 for
      TCAs versus SSRIs and SNRIs versus SSRIs). When categorized as inpatients (n =
      582) and outpatients (n = 1613), SNRIs had the highest remission rates (52.0% for
      144 inpatients and 49.3% for 559 outpatients). SNRIs had lowest overall dropouts
      (26.1%), followed by SSRIs (28.4%), and TCAs (35.7%). Dropouts due to ADRs and
      LoE were 10.3% and 6.2% for SNRIs, 8.3% and 7.2% for SSRIs, and 19.8% and 9.9%
      for TCAs, respectively (p > 0.05 for ADR dropouts only). One limitation was the
      inclusion of only venlafaxine-XR; results may not be the same for immediate
      release forms. In addition, few studies reported remission rates. CONCLUSIONS:
      SNRIs had the highest efficacy remission rates (statistically significant for
      inpatients and outpatients), and the lowest overall dropout rates, suggesting
      clinical superiority in treating major depression.

PMID- 16968587
TI  - Efficacy, tolerability, and parent reported outcomes for cefdinir vs. high-dose
      amoxicillin/clavulanate oral suspension for acute otitis media in young children.
AB  - OBJECTIVES: To compare efficacy, tolerability, and parental satisfaction of
      cefdinir and high-dose amoxicillin/clavulanate oral suspensions given to young
      children with non-refractory acute otitis media (AOM) based on clinical endpoints
      and outcomes measures. RESEARCH DESIGN AND METHODS: This was an investigator
      blinded, multicenter study in which 318 children 6 months through 6 years of age
      with a clinical diagnosis of AOM were randomized to receive 10 days of either
      cefdinir (14 mg/kg divided BID) or high-dose amoxicillin/clavulanate (90/6.4
      mg/kg divided BID). MAIN OUTCOME MEASURES: Investigators evaluated clinical
      response at an end-of-therapy (EOT) office visit conducted on day 12-15. Outcomes
      of satisfaction, tolerability, and adherence were also assessed at that visit
      using an Otitis Parent Questionnaire. RESULTS: The treatment groups were similar
      at baseline with respect to patient demographics. At the EOT visit, for cefdinir
      and amoxicillin/clavulanate, respectively, intent-to-treat (ITT) clinical cure
      rates were 82% (129/158) and 85% (134/158) (p = 0.547; 95% confidence interval
      [CI] -11.7 to 5.4) and per-protocol cure rates were 82% (123/150) and 90%
      (129/143) (p = 0.045; 95% CI -16.4 to 0.0). This difference was driven primarily
      by reduced cefdinir response in patients with recurrent AOM (p = 0.010) and those
      younger than 24 months (p = 0.039). Comparing cefdinir with
      amoxicillin/clavulanate, parents more often reported significantly better ease of
      use (89% vs. 57%; p < 0.0001), better taste (85% vs. 39%; p < 0.0001), and better
      adherence (at least 95% of doses) (82% vs. 61%; p < 0.0001). Diarrhea/loose
      stools were more common in the amoxicillin/clavulanate group than in the cefdinir
      group (28% vs. 18%, respectively; p = 0.0341). One patient in the cefdinir group
      and eight patients in the amoxicillin/clavulanate group withdrew from the study
      prematurely due to at least one adverse event (p = 0.0364). Study limitations
      included assessment of clinical recurrence by telephone call rather than office
      visit, exclusion of children with refractory AOM, and no assessment of middle ear
      microbiology. CONCLUSIONS: Among young children with non-refractory AOM, cefdinir
      was as efficacious as high-dose amoxicillin/clavulanate in the ITT group, but
      somewhat less effective in per-protocol analysis. From the parental perspective,
      cefdinir was easier to administer, had a better taste, caused less diarrhea, and
      resulted in higher treatment adherence than high-dose amoxicillin clavulanate.

PMID- 16968588
TI  - Efficacy and tolerability of the perindopril/indapamide combination therapy for
      hypertension: the PRIMUS study.
AB  - BACKGROUND: Tight blood pressure (BP) control is required to reduce
      cardiovascular morbidity and mortality. OBJECTIVE: To evaluate the efficacy and
      tolerability of the first line combination perindopril/indapamide in hypertension
      in daily practice. DESIGN AND METHODS: In this prospective, open-label,
      observational trial, 1892 general practitioners in Germany recruited patients
      with hypertension (n = 8023; mean age 59.6 years, 48.1% males, body mass index
      27.6 kg/m2, systolic BP >or= 140 mmHg and/or diastolic BP >or= 90 mmHg) between
      October 2002 and December 2004. Patients received perindopril 2 mg/indapamide
      0.625 mg for 12 weeks. BP measured in the general practice setting, safety, and
      tolerability were evaluated after 4 and 12 weeks. RESULTS: At baseline, most
      patients had moderate to severe hypertension (78%); initial BP was 164.6/95.8
      mmHg. At inclusion, 38% of the patients were newly diagnosed hypertensives (mean
      BP 166.1/97.2 mmHg) and 58% of patients had uncontrolled BP despite preexisting
      antihypertensive treatment (163.5/94.9 mmHg). Previous treatment consisted of
      beta-blockers (49.5%), ACE inhibitors (36.4%), calcium-antagonists (29.3%),
      diuretics (28.8%), AT-I receptor antagonists (7.1%), and other treatments (8.1%).
      In the entire study cohort, treatment with perindopril/indapamide significantly
      decreased systolic BP (27.9 mmHg), diastolic BP (13.7 mmHg), and pulse pressure
      (14.2 mmHg), compared with baseline (p < 0.0001); 96% of patients responded to
      treatment and in 50% of patients BP was normalized (< 140/90 mmHg). Treatment
      dose was doubled in 9.5% of patients. Similar results were found in various
      subgroup analyses (newly diagnosed patients, the elderly, and patients with
      isolated systolic hypertension, additional cardiovascular risk factors,
      associated diseases, or target organ damage). The most frequent adverse events (<
      1% of patients) were dry cough and nausea. CONCLUSIONS: The open-label,
      observational study PRIMUS, extends the existing evidence that the first line
      combination treatment of hypertension with perindopril/indapamide is effective,
      safe, and well tolerated in a representative cross-section of patients with newly
      diagnosed or pretreated but uncontrolled hypertension in daily practice.

PMID- 16968589
TI  - Survey of select practice behaviors by primary care physicians on the use of
      opioids for chronic pain.
AB  - OBJECTIVE: To assess the use of opioids by primary care physicians for the
      treatment of chronic pain. METHODS: A written survey was completed by 248 primary
      care physicians. Outcomes of interest included type of opioids prescribed, common
      pain diagnoses treated, opioid prescribing concerns, treatment of patients with a
      history of substance use disorders and clinic-based protocols for pain
      management. RESULTS: The mean age of the physicians who completed the
      questionnaire was 41 years. The majority were between the ages of 30 and 49 years
      (68%) with an equal number of men and women. Seventy percent were family
      physicians, 28.7% internists and less than 2% were community physicians and
      geriatricians. Physician concerns regarding opioid therapy included prescription
      drug abuse (84.2%), addiction (74.9%), adverse effects (68%), tolerance (60.7%),
      and medication interaction (32%). The survey found that the majority of the
      physicians were comfortable in prescribing narcotics to patients with terminal
      cancer. However, they were less comfortable prescribing narcotics to patients
      with low back pain and persons with a current or past history of drug or alcohol
      abuse. Physician management practices suggested that urine toxicology tests were
      under-utilized with only 6.9% reporting obtaining this test before prescribing
      opioids and only 15.0% performing urine toxicology tests on patients already
      prescribed opioids. Logistic regression analysis revealed that whether or not
      physicians routinely conducted urine toxicology screens was significantly (p =
      0.015) predicted by whether they had a system to track patients on opioids when
      prescribing narcotics. The primary limitation of the study is the reliance on
      physician self-report rather than objective measures of physician behavior.
      CONCLUSIONS: The survey suggests physicians are concerned about drug abuse,
      addiction, adverse effects, tolerance, and medication interaction. Their comfort
      level in prescribing opioids varies with the patient characteristics. Urine
      toxicology testing is underutilized in the primary care setting.

PMID- 16968590
TI  - [The international registry of clinical trials].

PMID- 16968591
TI  - Seroepidemiological profile of pregnant women after inadvertent rubella
      vaccination in the state of Rio de Janeiro, Brazil, 2001-2002.
AB  - OBJECTIVES: To analyze postvaccination serological status in pregnant women
      inadvertently vaccinated against rubella in the state of Rio de Janeiro, Brazil.
      METHODS: This was a cross-sectional study of pregnant women 15 to 29 years old,
      vaccinated against rubella and measles from November 2001 to March 2002, who were
      unaware of their pregnancy at the time of vaccination or who became pregnant
      within 30 days thereafter. They were tested for rubella-specific immunoglobulin M
      (IgM) and G (IgG) and classified as immune (IgM-negative, IgG-positive, tested
      within 30 days after vaccination), susceptible (IgM-positive after vaccination)
      or indeterminate (IgM-negative, IgG-positive, vaccination-serological testing
      interval greater than 30 days). RESULTS: Of 2 292 women, 288 (12.6%) were
      susceptible, 316 (13.8%) immune, 1 576 (68.8%) indeterminate, 8 (0.3%)
      ineligible, and 104 (4.5%) lost to follow-up. IgM seropositivity by vaccination
      serological testing interval was 16.1% (</= 30 days), 15.4% (30-60 days), and
      14.2% (61-90 days). Considering the campaign's target age, the 20-to-24-year age
      group had the largest proportion of individuals susceptible to rubella (14.8%)
      and represented 42.4% (122/288) of all susceptible women. In 75% of susceptible
      pregnant women, gestational age was 5 weeks or less at the time of vaccination.
      CONCLUSIONS: Mass immunization of childbearing-age women was justified on the
      basis of epidemiological and serological data. Follow-up of vaccinated pregnant
      women revealed no cases of congenital rubella syndrome due to rubella
      vaccination. However, the observed rate of congenital infection supports the
      recommendation to avoid vaccinating pregnant women, and to avoid conception for
      up to 1 month following rubella vaccination.

PMID- 16968592
TI  - [Ecological factors linked to the presence of Aedes aegypti larvae in highly
      infested areas of Playa, a municipality belonging to Ciudad de La Habana, Cuba].
AB  - OBJECTIVES: To identify local ecological factors that might have had an impact on
      the higher infestation rates by the vector mosquito Aedes aegypti seen in four
      urban health districts of Ciudad de La Habana, Cuba, and to determine the type of
      containers with the highest number of larvae. METHODS: This is a descriptive
      study that was carried out in four health areas (Docente, 28 de Enero, 26 de
      Julio, and 1. degrees de Enero) within Playa, a municipality belonging to Ciudad
      de La Habana, Cuba. These areas were chosen because of the persistent presence of
      the dengue vector throughout 2003. All buildings on the selected blocks were
      inspected between April 2004 and March 2005, and note was taken of existing water
      deposits (type, number, and location) and of surrounding ecological factors
      (existence of a patio and shade, the way tanks were covered, the presence of
      organic matter inside them, and the overall cleanliness of the dwelling). Using
      filtration, the mosquito larvae and pupae in each deposit were counted. Pupae
      were typified as to their taxonomic species under a stereoscopic microscope.
      RESULTS: The types of deposits where larvae and pupae of A. aegypti were most
      often found in all areas were low tanks and small artificial containers. In three
      of the study areas the greatest numbers of pupae were found in low tanks (88.6%,
      100%, and 56.6%), 90.9% of which were uncovered or only partially covered. On the
      other hand, in the fourth study area small artificial deposits were the most
      commonly infested (85.7%). A correlation was noted between the number of deposits
      in infested houses and the presence of a patio (chi(2) = 29.59; P = 0.0001),
      partial shade (chi(2) = 4.108; P = 0.0001), shrubbery (chi(2) = 43.59; P =
      0.0001) and trees (chi(2) = 101.459; P = 0.0001), as well as poor hygiene (chi(2)
      = 53.76; P = 0.0001). CONCLUSIONS: Artificial deposits, especially low tanks and
      small containers, are the most frequent breeding sites for A. aegypti and are
      therefore risk factors for infestation with this vector species. Uncovered tanks
      containing organic matter and located in the shade on the outside of homes were
      found to present the highest risk in this respect.

PMID- 16968593
TI  - [Dental caries in Brazil: decline, polarization, inequality and social
      exclusion].
AB  - OBJECTIVE: To examine the caries situation in Brazilian schoolchildren between
      1980 and 2003 and to determine the distribution of caries and access to treatment
      in this population group. METHODS: We employed secondary data concerning the
      number of decayed, missing or filled teeth (DMFT). The studies whose data were
      used differed in terms of study type, study design, sampling methods, and
      diagnostic criteria, but yielded national estimates that are considered valid for
      the DMFT index. Therefore, a trend analysis based on these studies was thought to
      be feasible. RESULTS: Analysis of DMFT values revealed a high frequency of dental
      caries in 1980 and a moderate frequency in the 1990s. In 2003, the DMFT index was
      still within the moderate range. Between 1980 and 2003, a 61.7% decrease in DMFT
      frequency was observed. The percentage of children with no DMFT increased from
      3.7% in 1986 to 31.1% in 2003. On the other hand, in the segment of the study
      population least affected, the percentage of children who received care increased
      from 26.3 in 1986 to 34.7 in 2003, yet in the group with DMFT this percentage
      fell from 50.2 in 1986 to 39.3 in 2003. In the segment with DMFT >/=6, the
      percentage of those who received care remained stable (28%). During the study
      period, 60% of the dental caries were found in 20% of the study population.
      CONCLUSION: An important decline in DMFT was observed between 1980 and 2003,
      perhaps as a result of increased access to fluoridated water and toothpaste and
      of changes in the goals of public oral health programs. Despite the improvement,
      caries is unevenly distributed in the pediatric population; a small proportion of
      individuals carries most of the disease burden. In addition, the proportion of
      teeth with caries that went untreated did not change between 1980 and 2003.
      Reducing socioeconomic disparities and adopting public health measures that
      target and reach the most vulnerable groups remain a challenge for policy makers
      in Brazil.

PMID- 16968594
TI  - [The treatment received by public health services users in Mexico].
AB  - OBJECTIVE: To document the fact that differences in the treatment received by
      health services users in Mexico are mainly dependent on the type of provider,
      regardless of the users' socioeconomic status. METHODS: The data were obtained by
      means of a survey of 18 018 users who visited 73 health services in 13 states
      within Mexico. They were asked to grade the way the institution had performed in
      seven of the eight domains that define appropriate user treatment (autonomy,
      confidentiality, communication, respectful manner, condition of basic facilities,
      access to social assistance networks, and free user choice). The questionnaire
      included some vignettes to help determine user expectations. A composite ordinal
      probit model was applied; the perception of quality in connection with each of
      the appropriate treatment domains was the independent variable, whereas gender,
      educational level, age, type of provider, and user expectations were used as
      control variables. RESULTS: The type of provider was the main factor that
      determined users' perceptions regarding the treatment they received when visiting
      health services in Mexico. Institutions belonging to the social security system
      performed the worst, while the services provided under the program targeting the
      rural population (IMSS Oportunidades) received the highest scores. Overall, the
      domain that was most highly ranked was respectful manner, whereas the lowest
      score was given to the ability to choose the provider. Men felt they had been
      able to communicate better than women, while respectful manner, communication,
      and social support showed a significant negative association with educational
      level (P < 0.05). CONCLUSIONS: Differences were noted in the way different public
      health service providers in Mexico treat their users, regardless of the latter's
      socioeconomic status. Social security system providers showed the greatest
      deficiencies in this respect. Respectful manner was the domain that received the
      highest scores in the case of all providers. Organizational changes need to be
      made, since the shortcomings detected are not solely determined by factors
      related to health personnel, but also by certain aspects of the way the health
      system is structured in Mexico.

PMID- 16968595
TI  - Tuberculin skin reactivity after neonatal BCG vaccination in preterm infants in
      Minas Gerais, Brazil, 2001-2002.
AB  - OBJECTIVES: The efficacy of BCG vaccination in preterm babies is unknown, and
      available data on conversion rates to tuberculin in this age group are scarce and
      controversial. This study assessed the tuberculin response in preterm infants
      after BCG vaccination. METHODS: This randomized cohort study was carried out at
      the Neonatal Department, University Hospital, Federal University of Minas Gerais
      in Brazil during 2001 and 2002. The BCG vaccine was administered at birth to 65
      full-term (control) and 40 preterm newborns. All of them were tested with 5
      tuberculin units of purified protein derivative-S approximately 3 months after
      vaccination. RESULTS: A typical BCG scar was verified in 96.9% of the control
      group and in 90.0% of the preterm infants (P = 0.19). Indurations > 5 mm in
      diameter were recorded in 87.7% of the full-term and 67.5% of the preterm infants
      (P = 0.02). Indurations > 10 mm were recorded in 70.8% of the full-term and 42.5%
      of the preterm infants (P = 0.007). For indurations > 5 mm the upper and the
      lower limits of the 95% confidence interval for the difference between
      proportions were 8.5% to 31.8%, and for indurations > 10 mm these limits were
      18.0% to 38.4%. No adverse reactions were observed in the study population.
      CONCLUSION: BCG vaccination could be recommended for preterm infants upon
      discharge from the neonatal unit to reduce morbidity and mortality in infants at
      risk for tuberculous infection, and to increase BCG vaccination coverage rates,
      especially in countries with high prevalence rates of tuberculosis.

PMID- 16968596
TI  - [Principles of the international registry of protocols and clinical trial results
      based on health interventions in human beings: Ottawa Declaration (part 1)].

PMID- 16968597
TI  - The Latin American Ongoing Clinical Trial Register (LATINREC).

PMID- 16968598
TI  - The structuring of health systems and the control of infectious disease: looking
      at Mexico and Cuba.

PMID- 16968599
TI  - Current status of gastric MALT lymphoma.

PMID- 16968600
TI  - Progress and pitfalls with IBD serologies.

PMID- 16968601
TI  - Biologic clocks and the gut.
AB  - The gastrointestinal tract displays biologic rhythms in basal gastric acid
      output, epithelial cell proliferation, gastrointestinal motility, and appetite
      regulation. Furthermore, the development of gastrointestinal complications after
      administration of aspirin and after chemo- and radiotherapy for metastatic colon
      cancer depends on the time of administration. Biologic rhythms are driven by so
      called clock genes. Thus, it is conceivable that subsets of genes in the
      gastrointestinal tract are under clock gene control as well. The purpose of this
      article is to discuss basic concepts in the studies of biologic rhythms, to
      review examples of biologic rhythms in the gastrointestinal tract, and to discuss
      examples of gastrointestinal diseases in which alterations in biologic rhythms
      may play a pathogenetic role.

PMID- 16968602
TI  - Small bowel transplantation.
AB  - Until very recently, outcomes from small bowel transplantation (SBTx) lagged
      behind those in liver, heart, and kidney transplantation because of the magnitude
      of the immunologic burden; the strong expression of histocompatibility antigens;
      and the contamination in grafts by bacterial organisms. With novel techniques of
      immune-induction therapies, such as recipient "preconditioning" with lymphocyte
      reduction, followed by the more subtle use of immunosuppression-based single
      agent tacrolimus, graft and host 1-year survival is now over 90% in the most
      active US centers, a finding that parallels the outcomes in liver and kidney
      transplantation. In contrast to the alternative therapy for permanent intestinal
      failure, home total parenteral nutrition (TPN), SBTx improves quality of life and
      restores digestive and absorptive function, making patients nutritionally
      autonomous. With survival beyond 1 to 3 years, the procedure is cost-effective.
      Current results support expansion of the indications for SBTx from use as salvage
      therapy for patients with TPN failure to preemptive therapy for patients at risk
      of developing TPN failure.

PMID- 16968603
TI  - Ileal brake: neuropeptidergic control of intestinal transit.
AB  - Digestion and absorption of a meal are time-intensive processes. To optimize
      digestion and absorption, transit of the meal through the gastrointestinal tract
      is regulated by a complex integration of neuropeptidergic signals generated as
      the jejunal brake and ileal brake response to nutrients. Mediators involved in
      the slowing of transit responses include peptide YY (PYY), chemosensitive
      afferent neurons, intestinofugal nerves, noradrenergic nerves, myenteric
      serotonergic neurons, and opioid neurons. The activation of this circuitry
      modifies the peristaltic reflex to convert the intestinal motility pattern from
      propagative to segmenting. Fat is the most potent trigger of these transit
      control mechanisms. The integrated circuitry of gut peptides and neurons involved
      in transit control in response to nutrients is described in this review.

PMID- 16968604
TI  - Food allergies.
AB  - Food incompatibilities affect approximately 20% of the general population in
      Western countries. In about one quarter of the affected children and one tenth of
      affected adults, the incompatibility is based on an allergy, that is, on an
      immunologically generated incompatibility reaction. Gastrointestinal symptoms
      occur in a third of these cases. Food allergies are caused by IgE-dependent orIgE
      independent immunologic reactions, which lead to an inflammatory reaction, in
      which mast cells, eosinophilic granulocytes, and other cells are involved. Both
      genetic and environmental causes are under consideration. New findings concerning
      the interaction between the innate immune system and intestinal microflora have
      generated innovative therapeutic concepts, including the use of probiotics to
      prevent food allergies. The development of recombinant allergens and varieties of
      allergens will improve diagnostic possibilities and bring new therapeutic
      options, such as hyposensitization and induction of immunologic tolerance. Food
      intolerances (non-immunologic food incompatibilities often caused by specific
      enzyme deficiencies) must be diagnostically differentiated from food allergies.

PMID- 16968606
TI  - Eosinophils in the gastrointestinal tract.
AB  - Although we know that eosinophils reside in the normal gastrointestinal tract and
      increase during inflammatory states, their exact role in gut homeostasis and in
      the pathogenesis of inflammatory processes is not certain. An increasing number
      of clinical reports suggest that eosinophils participate in the pathogenesis of
      mucosal inflammation, and emerging literature is beginning to define these
      mechanisms. For example, homing of eosinophils to the gastrointestinal tract is
      better understood with respect to the roles of specific eosinophilic attractants,
      such as the eotaxins and interleukin-5. As mechanisms of eosinophil recruitment,
      activation, and functional responses are further elucidated, novel targets for
      treatment strategies in specific diseases will likely follow. We review recent
      developments in eosinophil immunobiology as they relate to gastrointestinal
      inflammation and provide an update on clinical aspects of eosinophilic
      esophagitis as they relate to eosoinophilic diseases of the gastrointestinal
      tract.

PMID- 16968605
TI  - Extraintestinal manifestations of celiac disease.
AB  - Celiac disease is an autoimmune disorder that occurs in genetically predisposed
      individuals as the result of an immune response to gluten. It is present in
      approximately 1% of the population. Diarrhea has become a less common mode of
      presentation (<50% of cases) than it once was. Other presentations include iron
      deficiency anemia, osteoporosis, dermatitis herpetiforme, and neurologic
      disorders, mainly peripheral neuropathy and ataxia. Arthritis is commonly found
      in patients with celiac disease when systematically sought. Overall, autoimmune
      diseases occur more frequently (three to ten times more) in those with celiac
      disease than in the general population. A gluten-free diet is the standard of
      treatment, although its effect on some of the extraintestinal manifestations
      remains to be determined.

PMID- 16968607
TI  - Renal failure after bowel preparation with sodium phosphate.

PMID- 16968608
TI  - Norovirus gastroenteritis.
AB  - Recent epidemiologic studies have shown that norovirus is one of the most
      frequent causes of acute nonbacterial gastroenteritis. Reverse-transcription
      polymerase chain reaction and nucleotide sequencing are the means by which the
      hundreds of norovirus strains have been identified, named, and classified into
      genogroups and genetic clusters. They are also the means by which a particular
      strain is traced from the source of an outbreak throughout its spread. These
      molecular techniques have been combined with classic epidemiology to investigate
      norovirus outbreaks in diverse settings, including hospitals, nursing homes,
      dining locations, schools, daycare centers, and vacation venues. Outbreaks are
      difficult to control because of the apparent ease of transmission through food,
      water, person-to-person contact, and environmental surfaces. Almost all patients
      with norovirus gastroenteritis recover completely, but hospital and nursing home
      outbreaks have been associated with morbidity and mortality. The diagnostic and
      management approach to an individual patient is to use clinical and epidemiologic
      findings to rule out "not norovirus." At the first sign that there is an
      outbreak, strict compliance with cleaning, disinfection, and work release
      guidelines is important to prevent further spread.

PMID- 16968609
TI  - Recent advances in chromoscopic colonoscopy and endomicroscopy.
AB  - The basic rationale for secondary prevention of colorectal carcinoma is by
      endoscopic polypectomy. New technologies in the form of high-magnification or
      "zoom" colonoscopy complemented by chromoscopic agents permit early detection of
      neoplastic colorectal lesions, particularly flat and depressed types. Detailed
      morphologic characteristics of the surface crypt or "pit pattern" can be obtained
      with these techniques, enabling an in vivo "optical biopsy" and staging tool.
      Establishing suitability for endoscopic resection or surgical excision can be
      enhanced using these techniques. Furthermore, chromoscopic colonoscopy may have a
      role in routine endoscopic colorectal cancer surveillance programs in patients at
      high risk for colorectal neoplasia, such as those with long-standing ulcerative
      colitis and familial colorectal cancer syndromes. This review summarizes recent
      data regarding the prevalence and histopathologic characteristics of flat and
      depressed colorectal lesions in Western cohorts and describes how their detection
      and management can be improved by chromoscopy and magnification technology. We
      outline these techniques from a clinical perspective and describe the basic
      principles of endoscopic mucosal resection.

PMID- 16968610
TI  - Diagnostic testing in patients with chronic constipation.
AB  - During the past few years, significant developments have taken place in the
      understanding and diagnosis of defecation disorders. Several innovative
      manometric, neurophysiologic, and radiologic techniques have been discovered,
      which have improved the accuracy of identifying the neuromuscular and
      pathophysiologic mechanisms of chronic constipation. Such approaches have led to
      improved management of these patients. In this review, we summarize and highlight
      recent advances in the utility of diagnostic testing of chronic constipation.

PMID- 16968611
TI  - Adolescents and young adults with Hirschsprung's disease.
AB  - A majority of children and adolescents who have successful surgery to resect
      colon affected by Hirschsprung's disease suffer from digestive disorders,
      defecation problems, or both into adult life. In those with persistent symptoms
      following Hirschsprung's surgery, colon manometry facilitates a physiologic
      explanation for symptoms and guides treatment. Only a few patients born with
      Hirschsprung's disease make it to adult age before diagnosis and surgery, but
      their management does not differ from that of children with Hirschsprung's
      disease. The quality of life for patients with Hirschsprung's disease depends on
      psychosocial factors and not on childhood suffering or chronic symptoms.

PMID- 16968612
TI  - Colonoscopic polypectomy: a critical review of recent literature.
AB  - Colonoscopic polypectomy continues to be a major activity of gastrointestinal
      endoscopists, based upon the belief that ridding the colon of polyps prevents
      colon cancer. We review recent literature bearing on this assumption, emphasizing
      the benefits and limitations of colonoscopy for screening and surveillance of
      polyps. CT colonography has developed as an alternative or adjunct to colonoscopy
      but has not surpassed it in accuracy or therapeutic potential. Other recent
      technologic developments, such as magnification and chromoendoscopy, are
      reviewed, and an attempt is made to put them in perspective.

PMID- 16968613
TI  - Addressing the misuse and abuse of stimulant medications on college campuses.

PMID- 16968615
TI  - Continuing care in the treatment of addictive disorders.
AB  - Newer models of continuing care in the addictions are designed to improve the
      long-term management of substance use disorders by engaging patients into
      flexible, or "adaptive," treatment algorithms that change in focus and intensity
      as symptoms wax and wane over time. This article describes some of these newer
      approaches to the management of substance use disorders and presents recent
      research on their effectiveness. Findings suggest the following: 1) Continuing
      care interventions of a year or longer are more likely to show significant
      positive effects; 2) Continuing care treatments that are less burdensome to
      patients appear to promote higher rates of sustained engagement; 3) More
      structured and intensive continuing care may be more effective for patients with
      severe substance dependence and associated problems and for those who fail to
      achieve reasonable progress while in the initial phase of treatment; and 4) Use
      of medications as part of continuing care is increasing.

PMID- 16968614
TI  - Management of methamphetamine abuse and dependence.
AB  - Preliminary implications for evidence-based treatments and future practice may be
      drawn from new research findings that inspire a fresh view of methamphetamine
      dependence and associated medical consequences. Current user populations include
      increasingly impacted subgroups (ie, youths, women, men who have sex with men,
      and rural residents); complex consequences of methamphetamine abuse among these
      subgroups require additional efforts involving contextual understanding of
      characteristics and needs to develop effective treatments. The neurobiological
      data on cellular activity of methamphetamine taken with findings from
      neuroimaging studies indicate potential targets for pharmacologic interventions.
      In early trials, several candidate medications--bupropion, modafinil, and, to a
      lesser extent, baclofen--have shown promise in treating aspects of
      methamphetamine dependence, including aiding memory function necessary to more
      effectively participate in and benefit from behavioral therapies. Clinicians and
      researchers must interact to efficiently address the problems of methamphetamine
      dependence, a major drug problem in the United States and the world.

PMID- 16968616
TI  - Treating depression in substance abusers.
AB  - The literature on the diagnosis and treatment of depression is reviewed to arrive
      at recommendations for clinical practice, future research, and models of service
      delivery. The DSM-IV criteria are found to provide a sound basis for diagnosis,
      and a review of placebo-controlled trials of antidepressant medications among
      substance-dependent patients suggests medication is effective in the setting of
      careful diagnosis, preferably during a currently observed abstinent period.
      Clinical recommendations offered for the approach to patients with co-occurring
      depression and substance dependence include the following: 1) Initiate treatment
      for substance dependence and encourage abstinence; 2) Conduct a careful
      psychiatric history and apply DSM-IV criteria for primary or substance-induced
      depression; 3) If depression meets diagnostic criteria and persists despite
      treatment of substance use disorder, treat the depression. Future research should
      include trials of psychotherapeutic or behavioral treatments, studies of
      treatment algorithms and of integrated systems of care, and studies of methods
      for disseminating diagnostic and treatment methods in an effort to diminish
      traditional boundaries between the skill sets of mental health and substance
      abuse clinicians.

PMID- 16968617
TI  - Chronic pain and comorbid mood and substance use disorders: a biopsychosocial
      treatment approach.
AB  - Chronic pain is a colossal health care problem that is devastating to the
      individual afflicted with unremitting pain and frustrating to the beleaguered
      health care provider attempting to adequately manage this multifaceted disease.
      The biopsychosocial model of pain management is a promising approach that
      emphasizes evidence-based medication management in conjunction with cognitive
      behavioral therapy and a graded exercise program. The patient with chronic pain
      and concomitant mood and/or substance use disorders is exceptionally challenging.
      Effective pharmacologic management of pain and comorbid mood disorders, including
      the thoughtful use of opioids, can have a dramatic effect in improving the
      quality of life in patients with chronic pain. The high prevalence of chronic
      pain in our society and the scarcity of experienced pain medicine physicians
      necessitate the development of a community-based systems approach to this complex
      patient population.

PMID- 16968618
TI  - The Internet as a source of drugs of abuse.
AB  - The Internet is a vital medium for communication, entertainment, and commerce,
      with more than 1 billion individuals connected worldwide. In addition to the many
      positive functions served by the Internet, it also has been used to facilitate
      the illicit sale of controlled substances. No-prescription websites (NPWs) offer-
      and then actually sell--controlled substances over the Internet without a valid
      prescription. NPW monitoring studies have focused primarily on the availability
      of prescription opioid medications, although many other drugs of abuse also are
      available online. Research indicates that these NPW sites are prevalent. Google
      or Yahoo searches simply using the term "Vicodin" return 40% to 50% NPWs in the
      top 100 sites. Thus, NPWs represent an important development in the sale of
      illicit drugs because of the ease with which controlled substances can be sold
      with relative anonymity. The emergence of NPWs requires new law enforcement and
      public health initiatives; continued monitoring efforts will determine whether
      efforts to reduce the availability of NPWs are successful.

PMID- 16968620
TI  - Treating comorbid ADHD in adults: mixed results in recent clinical trials.

PMID- 16968619
TI  - Choosing the right medication for the treatment of alcoholism.
AB  - In the past decade, scientists have made important progress toward understanding
      the neurobiology underlying an alcohol disorder. This knowledge has led to the
      development of promising pharmacotherapies that target the neural pathways
      involved in the brain's reward center in such a way that the usual treatment
      response (via counseling) is substantially improved upon. There are now four US
      Food and Drug Administration (FDA)-approved pharmacotherapies for the treatment
      of alcohol dependence: disulfiram (Antabuse; Odyssey Pharmaceuticals, East
      Hanover, NJ), oral naltrexone (ReVia; Barr Pharmaceuticals, Inc., Pomona, NY),
      acamprosate (Campral; Forest Laboratories, Inc., New York, NY), and, as of April
      2006, an extended-release (30-day) injectable suspension formulation of
      naltrexone (Vivitrol; Alkermes, Inc., Cambridge, MA). Other types of medications
      (eg, topiramate and quetiapine) are currently under investigation for the
      treatment of alcohol dependence. Research also has provided insights into best
      practices for prescribing the available medications. This report reviews the
      latest innovations in pharmacotherapy for the treatment of alcohol dependence,
      focusing on FDA-approved medications presently available to the treatment
      community.

PMID- 16968622
TI  - The genetics of ADHD: a literature review of 2005.
AB  - Investigations into the genetic basis of attention-deficit/hyperactivity disorder
      (ADHD) continue to yield compelling results as candidate gene studies reveal more
      information about this elusive disorder. Family, twin, and adoption studies
      further the notion that ADHD is a highly heritable disorder with direct genetic
      and environmental influence. The year 2005 saw many ADHD candidate gene studies,
      with most focused on the catecholaminergic candidates. Although many genes were
      studied in 2005, a large portion of findings has been supportive of the roles of
      dopaminergic genes' relationship to clinical phenotypes and drug response. These
      studies often require replication. Clinical implications continue to be
      speculative, as larger sample sizes are needed to validate findings to the
      general population. Further understanding of endophenotypes and the impact of
      comorbidities also is necessary for proper clinical intervention. Forthwith, we
      provide a summary of ADHD genetic studies published in 2005.

PMID- 16968623
TI  - Long-term treatment of children and adolescents with attention
      deficit/hyperactivity disorder (ADHD).
AB  - Only 7% to 50% of children with attention-deficit/hyperactivity disorder actually
      are treated. Of those who begin treatment, only 18% to 50% persist in the
      treatment for any length of time (eg, 2 to 3 years). Thus, available data on
      effects of long-term medication and psychosocial treatment are sparse and
      problematic. This article reviews available data on long-term effects of
      medication (stimulant and nonstimulant) and psychosocial treatment.

PMID- 16968624
TI  - Combination pharmacotherapy for adult ADHD.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent
      neuropsychiatric disorders of adulthood. Although clinical guidelines recommend
      monotherapy with stimulants or atomoxetine, combination pharmacotherapy is a
      common practice among clinicians. There are four main situations in which
      combination medications may be necessary: partial response, dose-limiting side
      effects, associated disorders, and comorbid diagnoses. We present data from two
      chart reviews that support existing research on combination pharmacotherapy.
      Adjunct treatment of d-methylphenidate to stimulant medications extended the
      duration of therapeutic effect. Adjunct treatment of mirtazapine to stimulant
      medications reduced associated insomnia. These data support previous research
      that validates the use of combination pharmacotherapy for adults with ADHD.

PMID- 16968625
TI  - Attention-deficit/hyperactivity disorder (ADHD) and driving risk: a review of the
      literature and a methodological critique.
AB  - This article examines the literature on attention-deficit/hyperactivity disorder
      (ADHD) and unintentional driving injury. This literature has emerged over the
      last decade as part of the burgeoning epidemic of road traffic death and injury,
      which is the number-one cause of death among young adults in North America. The
      available literature on observational outcome studies and experimental
      pharmacologic interventions is critically reviewed. A meta-analysis of behavioral
      outcomes and a review of effect size of pharmacologic studies are presented.
      Current data support the utility of stimulant medication in improving driving
      performance in younger ADHD drivers. A conceptual model of risk factors in young
      ADHD drivers is offered. The current state of screening instruments for
      identifying high-risk subjects within this clinical group is summarized along
      with a final section on emerging trends and future prospects for intervention.

PMID- 16968626
TI  - Brain strains in vehicle impact tests.
AB  - The purpose of this research was to use vehicle impact test data and parametric
      finite element analysis to study the contribution of translational accelerations
      (TransAcc) and rotational accelerations (RotAcc) on strain-induced head injuries.
      Acceleration data were extracted from 33 non-contact vehicle crash tests
      conducted by the US Department of Transportation, National Highway Traffic Safety
      Administration. A human finite element head model was exercised using head
      accelerations from the nine accelerometer package placed inside the driver dummy
      in these tests. Three scenarios were parameterized: both TransAcc and RotAcc,
      only TransAcc, and only RotAcc to demonstrate the contribution of these
      accelerations on brain injury. Brain strains at multiple elements, cumulative
      strain damage, dilatation damage, and relative motion damage data were compared.
      Rotational accelerations contributed to more than 80% of the brain strain. Other
      injury metrics also supported this finding. These findings did not depend on the
      crash mode, peak amplitude of translational acceleration (29 to 120 g), peak
      amplitude of rotational acceleration (1.3 to 9.4 krad/s ( 2 ) ) or HIC (68-778).
      Rotational accelerations appeared to be the major cause of strain-induced brain
      injury.

PMID- 16968627
TI  - An experimental and computational study of blunt carotid artery injury.
AB  - A carotid artery dissection begins as a tear or defect of the intimal lining of
      the artery, and can lead to luminal occlusion and ultimately cerebral ischemia.
      Our aim is to conduct an organ level validation of a finite element model of the
      carotid artery using an experiment designed to elicit internal layer failure
      within fluid-filled carotid artery samples. A 2.4-kg beveled guillotine is
      dropped from three heights (0.3, 0.5 and 0.7 m) onto fluid-filled porcine carotid
      arteries and resulting damage is recorded. These events are modeled using finite
      element analysis. Stress, strain and strain rate are correlated to experimental
      outcome. Internal layer damage is reported in half of the experiments, with
      damage occurring with 100% frequency at a drop height of 0.7 m. Simulations of
      this experiment result in maximum principal stress and strain values of 1.43 MPa
      and 46.2% respectively. The strain level predicted by the model for this impact
      scenario approaches the strain to intimal failure level for porcine arteries
      found in the literature. The results of this study represent an important step in
      validating this finite element carotid artery model at the organ level.

PMID- 16968628
TI  - Factors related to fatal injury in frontal crashes involving European cars.
AB  - Despite considerable improvements in frontal impact crashworthiness, frontal
      crashes still account for a major number of front seat occupant fatalities in
      Great Britain. This study attempted to determine the remaining potential for
      further fatality reduction with passive safety improvements in frontal crashes.
      No evidence was found to support an increase in crash test speeds. Instead,
      assessment of scope for survival showed that at least 27% of all fatal drivers
      and 39% of all fatal front seat passengers have survival potential given
      attention to older occupant's chest injury tolerance and passenger compartment
      intrusion under 60 km/h. Considering only fatal frontal crashes that might be
      assessed with a barrier test, showed an estimated survival potential of at least
      49% of belted drivers and 60% of belted front seat passengers. The high
      proportion of unbelted fatalities suggested that targeting unbelted occupant
      protection could have additional benefit.

PMID- 16968629
TI  - Comparison of delta-v and occupant impact velocity crash severity metrics using
      event data recorders.
AB  - This research compares the ability of delta-V and the occupant impact velocity
      (OIV), a competing measure of crash severity, to predict occupant injury in real
      world collisions. A majority of the analysis is performed using 191 cases with
      vehicle kinematics data from Event Data Recorders (EDRs) matched with detailed
      occupant injury information. Cumulative probability of injury risk curves are
      generated using binary logistic regression for all data, a belted subset, and an
      unbelted subset. By comparing the available fit statistics and performing a
      separate ROC curve analysis, the more computationally intensive OIV is found to
      offer no significant predictive advantage over delta-V.

PMID- 16968630
TI  - The accuracy of WinSmash delta-V estimates: the influence of vehicle type,
      stiffness, and impact mode.
AB  - The objective of this paper is to investigate the accuracy of WinSmash delta-V
      estimates as a function of crash mode, vehicle body type, and vehicle stiffness.
      The accuracy of WinSmash delta-V estimates was evaluated for 121 NASS/CDS 2000
      2003 cases for which direct measurements of delta-V had been retrieved from an
      Event Data Recorder on the case vehicle. WinSmash was found to underestimate
      delta-V by 23% on average. WinSmash was found to be most accurate in crashes
      involving full frontal engagement of the vehicle structure. When using
      categorical stiffness coefficients, the accuracy of delta-V estimates was found
      to be a strong function of vehicle type. WinSmash underestimated delta-V for
      pickup trucks by only 3%, but underestimated delta-V for front-wheel drive cars
      by 31%. The use of vehicle-specific stiffness coefficients improved the accuracy
      of the longitudinal delta-V estimate. The single most important factor in
      improving WinSmash accuracy was the inclusion of restitution. After adjusting for
      restitution, WinSmash underestimated delta-V in frontal crashes by only 1% on
      average.

PMID- 16968631
TI  - Crash culpability and the role of driver blood alcohol levels.
AB  - Twenty years ago the American Medical Association reported the relationship
      between blood alcohol concentration (BAC) and crash causation. This study
      addresses culpability, age, gender and BAC in a population of drivers injured in
      motor vehicle crashes. Five years of hospital and crash data were linked, using
      probabilistic techniques. Trends in culpability were analyzed by BAC category.
      Given BAC level, the youngest and oldest drivers were more likely to have caused
      their crash. Women drivers had significantly higher odds of culpability at the
      highest BAC levels. Seatbelt use was also associated with culpability, perhaps as
      a marker for risk-taking among drinkers.

PMID- 16968632
TI  - Abdominal injury patterns in real frontal crashes: influence of crash conditions,
      occupant seat and restraint systems.
AB  - An in-depth study was conducted through the analysis of medical reports and crash
      data from real world accidents. The objective was to investigate the abdominal
      injury patterns among car occupants in frontal crashes. The influence of the type
      of restraint system, the occupant seat, the age and the crash severity was
      investigated. The results indicate that the risk of abdominal AIS 3+ injuries
      increased with crash severity and decreased with the introduction of belt
      retractors. Rear belted passengers were observed to be more likely injured than
      front belted occupants. The organs injured in frontal crashes for belted
      occupants were mainly hollow organs especially jejunum, ileum and mesentery.

PMID- 16968633
TI  - Incidence of thoracic and lumbar spine injuries for restrained occupants in
      frontal collisions.
AB  - The increased utilization of three-point restraint systems has greatly reduced
      the incidence of spinal injuries in motor vehicle accidents. Nevertheless,
      several studies which rely upon the National Automotive Sampling System (NASS)
      have documented lower thoracic and upper lumbar fractures in restrained occupants
      involved in frontal collisions of moderate severities. Although it has been
      postulated that the injury mechanism may be related to the occupant being out-of
      position or sitting in an unusual posture, conclusions with regard to the precise
      mechanism of injury are difficult due to the lack of information contained in the
      NASS database. In addition, previous studies have not reported statistical
      significance of these injuries. In this study, we combined statistical analysis
      of frontal collisions in the NASS database with the analysis of data acquired
      from sled and crash tests, which utilized anthropomorphic test devices (ATDs), in
      order to evaluate the incidence and potential injury mechanisms underlying
      thoracic and lumbar spine fractures in moderate frontal impacts. In the first
      portion of the study, we performed a statistical analysis of the NASS database to
      estimate the incidence rate of spinal fracture. This was complemented with
      measurements and analysis of lumbar spine load data derived from frontal sled and
      crash tests. Analysis of the NASS database demonstrated that thoracolumbar spinal
      injuries are rare when an occupant is restrained by a lap and shoulder belt, and
      are often accompanied by abdominal injury. The spinal loads measured during
      frontal impacts with restrained and nominally positioned ATDs were found to be
      well below injury thresholds. Our results also suggest that the potential for
      isolated fracture is increased when the geometry of occupant-to-restraint
      interaction is compromised, as occurs when an occupant submarines the lap belt.

PMID- 16968634
TI  - Classification of rollovers according to crash severity.
AB  - NASS/CDS 1995-2004 was used to classify rollovers according to severity. The
      rollovers were partitioned into two classes - rollover as the first event and
      rollover preceded by an impact with a fixed or non-fixed object. The populations
      of belted and unbelted were examined separately and combined. The average injury
      rate for the unbelted was five times that for the belted. Approximately 21% of
      the severe injuries suffered by belted occupants were in crashes with harmful
      events prior to the rollover that produced severe damage to the vehicle. This
      group carried a much higher injury risk than the average. A planar damage measure
      in addition to the rollover measure was required to adequately capture the crash
      severity of this population. For rollovers as the first event, approximately 1%
      of the serious injuries to belted occupants occurred during the first quarter
      turn. Rollovers that were arrested during the 1 ( st ) quarter-turn carried a
      higher injury rate than average. The number of quarter-turns were grouped in
      various ways including the number of times the vehicle roof faces the ground
      (number of vehicle inversions). The number of vehicle inversions was found to be
      a statistically significant injury predictor for 78% of the belted and unbelted
      populations with MAIS 3+F injuries in rollovers. The remaining 22% required crash
      severity metrics in addition to the number of vehicle inversions.

PMID- 16968635
TI  - Implications of vehicle roll direction on occupant ejection and injury risk.
AB  - Vehicle roll direction and occupant position have been shown to affect occupant
      kinematics. Data from NASS-CDS were analyzed for risk of serious or greater
      injuries and ejection with respect to the position of the occupant (near side or
      far side). The risk of AIS 3+ injuries was higher for unrestrained occupants, for
      ejected occupants, for occupants involved in rollovers with higher numbers of
      quarter turns, and for far side occupants. Near side occupants had an increased
      risk of partial ejection in rollovers consisting of one complete roll or less.
      Occupant roll direction did not affect risk of complete ejection.

PMID- 16968636
TI  - Effect of model year and vehicle type on rollover crashes and associated injuries
      to children.
AB  - In child-involved crashes, there was a greater risk of rollover in pickups and
      SUVs than in passenger cars and minivans. Risk of injury to the corresponding
      child occupants in rollovers was significantly higher than for those in non
      rollover crashes. There has been little change in overall rollover rates for
      passenger cars, pickup trucks, and minivans in the most recent model years (since
      2002); however, there has been evidence of a declining rollover rate in SUVs
      during this same period. Even with this decline in SUV rollover risk, similarly
      aged passenger cars and minivans still exhibited a rollover risk approximately
      half that of their SUV counterparts.

PMID- 16968637
TI  - Analysis of pregnant occupant crash exposure and the potential effectiveness of
      four-point seatbelts in far side crashes.
AB  - The purpose of this paper is to present the crash exposure patterns of pregnant
      occupants and to evaluate the effectiveness of restraint systems, including four
      point seatbelts, in far side crashes. The NASS CDS database revealed that 53.0 %
      of pregnant occupants are exposed to frontal crashes while 13.5 % are exposed to
      far side impacts. Given that far side crashes were the second leading crash mode
      after frontal impacts, a previously validated MADYMO computer model of a 30 week
      pregnant occupant was utilized to investigate pregnant occupant biomechanics in
      far side crashes. Three impact speeds (5, 15, and 25 mph) were simulated with
      four restraint conditions: unbelted, lap-belt only, three-point belt, and a four
      point belt. Direct abdominal contact from the shoulder strap of the three-point
      or four-point belt caused uterine-placental strain in contrast to the inertial
      loading induced strain in the lap-belt and unbelted cases. Overall, the three
      point and four-point belt systems provide superior restraint effectiveness for
      the pregnant occupant compared to the lap-belt and no restraint cases. The four
      point resulted in slightly better performance than the three-point belt by
      reducing the fetal injury risk and occupant excursion.

PMID- 16968638
TI  - Worldsid assessment of far side impact countermeasures.
AB  - Far side impact trauma has been demonstrated as a significant portion of the
      total trauma in side impacts. The objective of the study was to assess the
      potential usefulness of countermeasures and assess the trade-offs associated with
      generic countermeasure design. Because the WorldSID dummy has demonstrated
      promise as a potential far side impact dummy, it was chosen to assess
      countermeasures in this mode. A unique far side impact buck was designed for a
      sled test system that included, as a standard configuration, a center console and
      outboard three-point belt system. This configuration assumed a left side driver
      with a right side impact. The buck allowed for additional options of generic
      restraints including shoulder or thorax plates or an inboard shoulder belt. The
      entire buck could be mounted on the sled in either a 90-degree (3-o'clock PDOF)
      or a 60-degree (2-o'clock PDOF) orientation. A total of 19 WorldSID tests were
      completed. The inboard shoulder belt configuration produced high shear forces in
      the lower neck (2430 N) when the belt position was placed over the mid portion of
      the neck. Shear forces were reduced and of opposite sign when the inboard belt
      position was horizontal and over the shoulder; forces were similar to the
      standard outboard belt configuration (830 - 1100 N). A shoulder or thorax
      restraint was effective in limiting the head excursion, but each caused
      significant displacement at the corresponding region on the dummy. A shoulder
      restraint resulted in shoulder displacements of 30 - 43 mm. A thorax restraint
      caused thorax deflections of 39 - 64 mm. Inboard restraints for far side impacts
      can be effective in reducing head excursion but the specific design and placement
      of these restraints determine their overall injury mitigating characteristics.

PMID- 16968639
TI  - Kid in the middle: a discussion of effectiveness of center rear-seat restraint
      systems.
AB  - This paper examines effectiveness of rear seat restraint systems in reducing
      injury in frontal and side impacts. Results indicate effectiveness varies by
      crash configuration and occupant age, with age being the most important factor
      influencing odds of fatality/serious injury to belted, rear seated occupants in
      frontal and side crashes. There is no significant difference between center lap
      and outboard lap/shoulder belts effectiveness; however, field data shows a high
      percentage of misuse (wearing belts improperly or using age-inappropriate belts)
      associated with fatalities and serious injuries. Review of NASS/CDS cases on
      seriously injured belted children shows belt misuse and injury patterns that
      might be mitigated by booster seats or proper use of adult belts.

PMID- 16968640
TI  - Injury patterns and severity among hospitalized motorcyclists: a comparison of
      younger and older riders.
AB  - In recent years there has been a significant increase in mortality among
      motorcyclists, especially older riders (40+ years). However, few studies have
      compared the nature and severity of injuries sustained by older vs. younger
      cyclists. The purpose of this analysis was to determine differences, if any, in
      injury patterns to older vs. younger motorcyclists and to explore rider, vehicle,
      and environmental factors associated with these differences. Older riders were
      found to have a significantly higher incidence of thoracic injury, especially
      multiple thoracic injuries, and specifically multiple rib fractures. Older
      motorcyclists were also more likely to ride larger motorcycles, and were more
      involved in collisions involving overturning or striking highway structures.
      Large engine sizes were associated with increased risk of head and thoracic
      injuries, but not abdominal injuries. The magnitude of increased risks related to
      1000+ cc engine size was higher among older motorcyclists than younger
      motorcyclists.

PMID- 16968641
TI  - Quality of life outcomes in a hospitalized sample of road users involved in
      crashes.
AB  - A follow-up study of road injury survivors admitted to hospital was conducted in
      the UK. The outcomes of road injury and their impact on quality of life were
      assessed using the SF-36v2, EQ-5D and CES-D scales. Lower extremity injury
      predominated (73%) in the study. Furthermore, there was a substantial impact on
      physical activity, large injury costs and potentially high QALY losses. Analysis
      of psychological effects found that females had higher levels of depression
      compared to males. This study identifies the consequences of road injury on
      individuals, highlighting the effective use of health outcome scales to quantify
      the quality of life changes over a 1-year period.

PMID- 16968642
TI  - Consensus or data-derived anatomical severity scoring?
AB  - We aimed to compare the predictive accuracy of consensus-derived and data-derived
      injury severity scores when considered alone and in combination with age and
      physiological status. Analyses were based on 25,111 patients. The predictive
      validity of each severity score was evaluated in logistic regression models
      predicting in-hospital mortality using measures of discrimination and
      calibration. Data-derived scores had consistently better predictive accuracy than
      consensus-derived scores in univariate models (p<0.0001) but very little
      difference between scores was observed in models including information on age and
      physiological status. Data-derived scores provide more accurate mortality
      prediction than consensus-derived scores when only anatomic injury severity is
      considered but offer little advantage if age and physiological status are taken
      into account.

PMID- 16968643
TI  - An approach to the derivation of the cost of UK vehicle crash injuries.
AB  - An approach to costing of road crash injury has been developed using data from a
      'Willingness-to-pay' survey mapped to injuries listed in the Abbreviated Injury
      Scale 1998 Revision. The costs derived have been applied to a database of real
      world crash injuries that have been collected as part of the UK Cooperative Crash
      Injury Study (CCIS). The approach has been developed in order to determine future
      research priorities in vehicle passive safety. When all injuries in all crash
      types are examined, the results highlight the cost of 'Whiplash' in the UK. When
      more serious injuries are considered, specifically those at AIS 2+, the cost of
      head injuries becomes evident in both frontal and side impacts.

PMID- 16968644
TI  - Anxiety, acute- and post-traumatic stress symptoms following involvement in
      traffic crashes.
AB  - Anxiety and traumatic stress symptoms are common post-crash. This study documents
      generalised anxiety responses post-crash, and examines the association between
      Acute Stress Disorder and Post-Traumatic Stress Disorder (PTSD) with personality
      and coping styles. Sixty-two patients aged 18-60 admitted to hospital were
      interviewed prior to discharge, at 2-months and at 6-8 months post-crash. Anxiety
      symptoms were common, with 55% of participants experiencing moderate-severe
      levels prior to discharge, with this decreasing to 11% and 6.5% at 2-months and 6
      8 months post-discharge. Females reported significantly higher levels of anxiety
      and acute distress. Neuroticism and generalised coping styles were associated
      with acute stress responses but not PTSD. These results have important
      theoretical and practical implications, and indicate that females are at risk of
      poorer acute anxiety outcomes following injury.

PMID- 16968645
TI  - Deriving and validating a road safety performance indicator for vehicle fleet
      passive safety.
AB  - Road safety performance indicators (RSPI) are policy tools which describe the
      extent of insecure operational safety conditions within traffic systems. This
      study describes the production of an RSPI which represents the presence within a
      country's vehicle fleet, of vehicles that may not effectively protect an occupant
      in a collision. This work is highly original, as it uses the entire vehicle
      database of European Union Member States in order to estimate the average level
      of passive safety offered by the entire fleet in each country. The EuroNCAP
      safety ratings and vehicle age of each vehicle in each fleet have been obtained
      to calculate the RSPI. The methodology used could be adopted as an international
      standard.

PMID- 16968646
TI  - High risk characteristics for motor vehicle crashes in persons with diabetes by
      age.
AB  - Studies highlight a higher involvement of drivers with diabetes in motor vehicle
      accidents. Extensive debate, though, exists over the most appropriate approach to
      license these drivers. Risk factors for crashes in persons with diabetes are not
      well defined. In this report, motor vehicle crash involvement was identified in
      two cohorts of persons with type 1 diabetes to identify if crash patterns and
      characteristics differ by age. Overall, reported crashes decline with age in
      persons with and without diabetes, but the crash risk remained higher for persons
      with diabetes throughout the age span. No relationship was observed between
      diabetes complications, blood glucose control, and diabetes treatment patterns
      and motor vehicle crashes. Severe hypoglycemia, though, was consistently and
      strongly related to crashes at all ages. The findings suggest that the crash risk
      related to hypoglycemia does not diminish markedly in persons with Type 1
      diabetes, despite changes in health and age. Several reports highlight the
      involvement of drivers with diabetes in motor vehicle crashes [Charlton, 2004].
      Extensive debate exists, though, over the role of diabetes in these crashes and
      licensing policy differs, worldwide, for these drivers. The natural history of
      type 1 diabetes (worsening health outcomes over time) indicates that factors
      influencing crashes in persons with diabetes may change over time. Few reports,
      though, have examined the factors related to crashes in persons with diabetes by
      age.

PMID- 16968647
TI  - Residual injuries after recent safety improvements.
AB  - This study examines the residual injuries reported in NASS/CDS 1997-2004 by crash
      mode, crash severity, body region and occupant age. It examines how serious
      injuries are distributed in present day crashes and identifies opportunities for
      further injury reduction. In planar crashes, approximately 66% of the MAIS 3+
      injuries occur in crashes less severe than 25 mph delta-V. Chest injuries
      predominate in these crashes, particularly among elderly occupants. A reduction
      in chest injuries to belted elderly occupants during low severity frontal crashes
      offers a prime opportunity for further improvement of safety systems. Younger
      occupants could also benefit from improved chest protection.

PMID- 16968648
TI  - High back booster seats: in the field and in the laboratory.
AB  - High back booster (HBB) seat use was studied in the field and in the laboratory.
      This paper presents details of a case series of 19 children using HBBs in real
      world crashes. More than half were using HBBs when a forward facing restraint
      would have been more suitable (i.e. inappropriately), and incorrect use was
      identified in 3 cases. All serious injury occurred in children inappropriately or
      incorrectly using HBBs. Laboratory simulations modelled on real world cases
      demonstrate a greater injury potential in misused HBBs than in correctly used
      HBBs due to excessive upper body excursion.

PMID- 16968649
TI  - Quantifying the relationship between vehicle interior geometry and child
      restraint systems.
AB  - The prevention of interactions of children or child restraints with other vehicle
      structures is critical to child passenger safety. Fifteen current vehicles and
      seven rear and forward facing child restraint systems were measured in an attempt
      to quantify the available distance between child restraints and these vehicle
      structures. Rear facing child restraints exhibited such small amounts of
      clearance that contact would be expected in the majority of frontal crashes.
      Upper tethers are critical in the prevention of head contact, while head contact
      is likely when the upper tether is not used.

PMID- 16968650
TI  - The effects of tethering rear -facing child restraint systems on ATD responses.
AB  - A series of sled tests was performed to analyze the responses of an
      anthropomorphic test device (ATD), particularly neck forces, when rear-facing
      child restraint systems (CRS) are tethered. Nominally identical rear-facing CRS
      were tested in four tether conditions: untethered, tethered down to the floor,
      tethered down to the bottom of the vehicle seat, and tethered rearward to a point
      above the back of the vehicle seat. The CRABI 12MO ATD with head, upper neck, and
      chest instrumentation was used in all tests. The tests were conducted using the
      ECE R44.02 test bench. Both frontal and rear impacts were performed and each
      condition was repeated for a total of 16 sled tests. Motions of the CRS and ATD
      were recorded using high-speed digital video (1000 fps). The highest ATD
      accelerations, forces, and moments were observed during the primary impact of a
      frontal test, rather than on rebound. The loads observed during rebound from
      frontal impact were similar in magnitude to the peak loads collected during rear
      impact. The four tethering geometries produced distinct loading patterns. The
      lowest HIC, neck forces, and chest accelerations in both impact directions were
      observed with the rearward tether. The upper neck moment data did not show a
      clear trend relative to tethering geometry. ATD and CRS motions were best
      controlled in frontal impact by the rearward tethering geometry while the motions
      in rear impact were best controlled by tethering to the floor. The data show a
      potential benefit in both frontal and rear impacts of tethering rear-facing CRS
      to a point above the vehicle seatback.

PMID- 16968651
TI  - Induction of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs
      correlates with outcome of acute experimental pseudomonal keratitis.
AB  - This study aimed to investigate expressions and sources of matrix
      metalloproteinases (MMP)-2 and MMP-9, and of tissue inhibitors of MMP (TIMP)-1
      and TIMP-2 in experimental Pseudomonas aeruginosa keratitis in rabbits.
      Pseudomonal keratitis was induced in New Zealand white rabbits, and macroscopic
      and microscopic examinations were performed at appropriate time points (3, 9, 12,
      18, 24, 72 h). Expressions and sources of MMP-2, 9, and TIMP-1, 2 were determined
      using immunohistochemistry, gelatin zymography, ELISA, and RT-PCR. A typical
      corneal ulcer with a ring abscess was observed 12-72 h post-infection (p.i.) with
      P. aeruginosa. In microscopic examinations, massive inflammatory cell (mostly
      polymorphonuclear leukocytes, PMNs) infiltration and liquefactive necrosis were
      characteristic features. MMP-2 was constitutively expressed in keratocytes, and
      its expression was not apparently enhanced after pseudomonal infection as
      evidenced by zymography, immunostaining, and RT-PCR. However, MMP-9 and its
      activated form were induced, and were significantly enhanced 12-24 h p.i. MMP-9
      appeared to derive from PMNs rather than from resident corneal cells. TIMP-1 was
      expressed in PMNs, macrophages, and keratocytes, and its expression was enhanced
      72 h p.i. Although TIMP-2 was constitutively expressed as seen by immunostaining
      and RT-PCR, its concentration was below detection limits during the experiments.
      We demonstrated that MMP-9 was one of the important factors for corneal tissue
      destruction, because it was induced and significantly expressed in keratocytes
      and inflammatory cells after pseudomonal infection. Although TIMP-1 was expressed
      in later stages of infection, enhancement and activation of MMP-9 were much
      faster and stronger than those of TIMP-1, thereby facilitating tissue destruction
      leading to corneal ulceration.

PMID- 16968652
TI  - Variation in brain size and ecology in Pongo.
AB  - Numerous hypotheses have been advanced to explain relative increases in brain
      size in primates and other mammals. However, notably less attention has been
      directed towards addressing the biological limits to increasing brain size. Here
      we explore variation in brain size in orangutans. We evaluated both raw and size
      adjusted cranial capacity (CC) in adult Pongo pygmaeus pygmaeus (n=147), P. p.
      wurmbii (n=24), P. p. morio (n=14), and P. abelii (n=36). Results demonstrate
      significant variation in CC among orangutan taxa. Population differences in raw
      CC are significant for females (p=0.014) but not males. Post-hoc pairwise
      comparisons among females further reveal that raw CC is significantly smaller in
      P. p. morio compared to both P. abelii and P. p. pygmaeus. When evaluated for
      proportionality, geometric equivalence in CC is not maintained in orangutans, as
      P. p. morio has a significantly smaller CC when compared to one or more other
      orangutan groups. Even after statistically partitioning size and size-correlated
      shape, P. p. morio has a significantly smaller CC compared to most other
      orangutan groups. These observed differences in relative brain size are
      consistent with known variation in resource quality and life history amongst
      orangutan populations. Specifically, P. p. morio is characterized by the least
      productive habitat, the lowest energy intake during extended lean periods, and
      the shortest interbirth intervals. Our results, therefore, provide conditional
      support for the hypothesis that decreased brain size is related to prolonged
      episodes of food scarcity, and suggest a correlation between brain size, diet
      quality, and life history at the lowest macroevolutionary level. The association
      of a relatively small brain and poor diet quality in Pongo further suggests that
      ecological factors may plausibly account for such a reduction in brain size as
      observed in the recently recovered Homo floresiensis from Indonesia.

PMID- 16968653
TI  - Designed ATRA analogue active against ATRA-resistant acute promyelocytic leukemia
      cells having a single nucleotide substitution in their retinoic acid receptor.
AB  - All-trans retinoic acid (ATRA) induces the differentiation of acute promyelocytic
      leukemia (APL) cells into neutrophils. UF-1 cells were established from an ATRA
      resistant APL patient, and were previously shown to possess a single amino acid
      (or nucleotide) substitution, Arg276Trp, in their ATRA receptor. In the present
      research, we designed several ATRA derivatives having a hydrophobic alkyl ketone
      moiety instead of the negatively charged carboxylic acid moiety. Among them the
      ethyl ketone derivative, Et-ketone ATRA, was shown to induce the differentiation
      of UF-1 cells when assessed in terms of intracellular ROS production. It also
      induced the formation of PML NBs and expression of CD11b antigen marker and p21,
      transcriptional targets of RARalpha. Et-ketone ATRA did not induce these
      phenotypic changes in wild-type APL NB4 cells. Furthermore, we found that Et
      ketone ATRA induced apoptosis selectively in UF-1 cells, i.e., not in other
      leukemic cells. The induction of apoptosis was shown to be partly due to the up
      regulation of Bax protein. Thus, Et-ketone ATRA selectively induced
      differentiation and apoptosis in ATRA-resistant APL UF-1 cells, and is likely to
      be useful for the clinical treatment of the Arg276Trp-type of ATRA-resistant APL.

PMID- 16968654
TI  - Detection of bocavirus DNA in nasopharyngeal aspirates of a child with
      bronchiolitis.
AB  - We describe a case of bronchiolitis associated with the newly detected human
      bocavirus (hBoV) in a child with a suspected Noonan syndrome. This is the first
      report of a bronchiolitis probably linked to hBoV that required intensive care
      while being accompanied by a congenital heart disease and a history of several
      episodes of severe respiratory symptoms.

PMID- 16968655
TI  - Hydromineral balance in the marine gulf toadfish (Opsanus beta) exposed to
      waterborne or infused nickel.
AB  - The effects of acute Ni exposure on the marine gulf toadfish (Opsanus beta) were
      investigated via separate exposures to waterborne nickel (Ni) and arterially
      infused Ni. Of the plasma electrolytes measured after 72 h of waterborne exposure
      (215.3 and 606.1 microM Ni in SW (salinity of 34)), only plasma [Ca2+] was
      significantly impacted (approximately 55% decrease at both exposure
      concentrations). At both exposure concentrations, plasma [Ni] was regulated for
      24h, after which a linear accumulation over time occurred. Accumulation of Ni in
      the plasma, and in tissues in direct contact with seawater (gill, stomach, and
      intestine), was roughly proportional to the Ni concentration of the exposure
      water. Hydromineral balance in the intestinal fluid (IF) was markedly impacted,
      with Na(+), Cl(-), SO(4)(2-), K+, and Mg2+ concentrations elevated after 72 h of
      exposure to waterborne Ni. Following arterial Ni infusion (0.40 micromolNikg(
      1)h(-1)), perturbation of hydromineral balance of the intestinal fluid was
      specific only to Na+ (significantly elevated by Ni infusion) and Mg2+
      (significantly decreased by Ni infusion). Nitrogen excretion was not
      significantly impacted by Ni infusion. In all tissues save the kidney, Ni
      accumulation via infusion was only a fraction of that observed during waterborne
      exposures. Remarkably, the kidney Ni burden following infusion was almost
      identical to that resulting from both waterborne exposures, suggesting
      homeostatic control. Ni excretion, dominated at 24 h by extrarenal routes, was
      primarily a function of renal excretion by 72 h of infusion. The sum excretion
      from infused toadfish was relatively efficient, accounting for over 40% of the
      infused dose by 72 h. Mechanistic knowledge of the mechanisms of toxicity of
      waterborne Ni in marine systems is a critical component to the development of
      physiologically based modeling approaches to accurately predict Ni toxicity in
      marine and estuarine ecosystems.

PMID- 16968656
TI  - Acute onset of type 1 diabetes accompanied by acute hepatitis C: the potential
      role of proinflammatory cytokine in the pathogenesis of autoimmune diabetes.
AB  - A 22-year-old Japanese woman presented with general fatigue. Five days later, she
      demonstrated a body temperature of 39 degrees C and a loss in weight of 5kg. She
      thereafter became unconscious and was taken to Tomakomai City General Hospital.
      Urinary ketone body was positive, and plasma glucose was 1063mg/dl. The serum
      asparate aminotransferase and alanine aminotransferase levels were 158 and
      1220IU/l, respectively. An arterial blood gas analysis showed metabolic acidosis.
      Glycated hemoglobin was 10.9%. Urinary C-peptide immnoreactivity was
      11microg/day. Anti-glutamic acid decarboxylase antibody was 12.4U/ml. In general,
      islet-associated autoantibodies are detectable several years before the
      development of overt autoimmune diabetes, thus suggesting that an autoimmune
      reaction against beta-cells had already started in this case. On viral
      examinations, hepatitis C virus (HCV) antibody was negative, while HCV-RNA was
      positive. Based on these findings, she was diagnosed to have autoimmune diabetes
      and acute hepatitis C. In addition, her serum interleukin-18 level was elevated
      to 506pg/ml. The duration of diabetic characteristic symptoms before diagnosis is
      usually several weeks in most cases of autoimmune diabetes. However, it was
      extremely short in this case. Taken together, these findings suggested that the
      progression of autoimmune diabetes might have been accelerated due to the
      infection of HCV.

PMID- 16968657
TI  - A vaccine cold chain freezing study in PNG highlights technology needs for hot
      climate countries.
AB  - Fourteen data loggers were packed with vaccine vials at the national vaccine
      store, Port Moresby, Papua New Guinea (PNG), and sent to peripheral locations in
      the health system. The temperatures that the data loggers recorded during their
      passage along the cold chain indicated that heat damage was unlikely, but that
      all vials were exposed to freezing temperatures at some time. The commonest place
      where freezing conditions existed was during transport. The freezing conditions
      were likely induced by packing the vials too close to the ice packs that were
      themselves too cold, and with insufficient insulation between them. This
      situation was rectified and a repeat dispatch of data loggers demonstrated that
      the system had indeed been rectified. Avoiding freeze damage becomes even more
      important as the price of freeze-sensitive vaccines increases with the
      introduction of more multiple-antigen vaccines. This low-cost high-tech method of
      evaluating the cold chain function is highly recommended for developing and
      industrialized nations and should be used on a regular basis to check the
      integrity of the vaccine cold chain. The study highlights the need for
      technological solutions to avoid vaccine freezing, particularly in hot climate
      countries.

PMID- 16968658
TI  - Vaccination with recombinant fusion proteins incorporating Toll-like receptor
      ligands induces rapid cellular and humoral immunity.
AB  - Recognition of specific pathogen associated molecular patterns (PAMPs) is
      mediated primarily by members of the Toll-like receptor (TLR) family. Stimulation
      through these receptors results in quantitative and qualitative changes in
      antigen presentation and cellular activation, thereby linking innate and adaptive
      immunity. Consequently, the incorporation of TLR-ligands into vaccines could
      result in more potent and efficacious vaccines. To test this hypothesis, we
      employed a recombinant fusion protein strategy using the TLR5 ligand flagellin
      fused to specific antigens to promote protective immunity. These purified
      recombinant fusion proteins demonstrated potent TLR5-specific NF-kappaB dependent
      activity in vitro. Immunization of mice with the recombinant-flagellin-OVA fusion
      protein STF2.OVA resulted in potent antigen-specific T and B cell responses that
      were equal to or better than responses induced by OVA emulsified in Complete
      Freund's adjuvant. These included rapid and consistent antigen-specific IgG(1)
      and IgG(2a) antibody responses that were detectable within 7 days of
      immunization, and the development of protective CD8 T cell responses. Moreover,
      the enhanced immunogenicity to OVA is dependant on the direct fusion to
      flagellin, as co-delivery of OVA with flagellin unlinked failed to augment
      antigen-specific responses in vivo. Similar results were obtained using a
      recombinant fusion protein comprised of flagellin and a novel polypetide sequence
      containing two immuno-protective epitopes derived from the Listeria monocytogenes
      antigens p60 and listeriolysin O. Animals immunized with this recombinant protein
      demonstrated significant antigen-specific CD8 T cell responses and protection
      upon challenge with virulent L. monocytogenes. We conclude that immunization with
      PAMP:antigen fusion proteins induce rapid and potent antigen-specific responses
      in the absence of supplemental adjuvants. Collectively our data demonstrate that
      PAMP:antigen fusion proteins offer significant promise for developing recombinant
      protein vaccines.

PMID- 16968659
TI  - Use of surfactants as plasticizers in preparing solid dispersions of poorly
      soluble API: selection of polymer-surfactant combinations using solubility
      parameters and testing the processability.
AB  - Formation of solid dispersions as a means to enhance the dissolution rate of
      poorly soluble Active pharmaceutical ingredients (APIs) typically employs
      hydrophilic polymer systems and surfactants. While the utility of the surfactant
      systems in solubilization is well known, the secondary effects of the same on
      processing and subsequent physical stability of the solid dispersions needs to be
      studied further. Physical blends of the poorly soluble API and hydrophilic
      polymers such as PVP-K30, Plasdone-S630, HPMC-E5, HPMCAS, and Eudragit L100 with
      mass ratio 1:1 were prepared. The surfactants tested in this study included Tween
      80, Docusate sodium, Myrj-52, Pluronic-F68 and SLS. Thermal analysis of the API
      polymer-surfactant blends suggested that the surfactants caused
      solvation/plasticization, manifesting in reduction of (i) the melting (T(m)) of
      API (ii) T(g) of the polymers and (iii) the combined T(g) of the solid dispersion
      formed from quench cooling. Explanation of these effects of surfactants is
      attempted based on their physical state (at the temperature of interest), HLB
      values and similarity of their solubility parameter values with respect to drug
      polymer systems. Furthermore, extruded matrices containing different API-polymer
      (PVP-K30, Plasdone-S630, and HPMC-E5) mixtures prepared with and without
      surfactants, were produced by feeding the powder blend through a hot-melt
      extruder. The melt viscosity of the polymer blends was assessed by torque
      rheometry using a Haake Rheomix. The physicochemical properties of the extruded
      API-polymer-surfactant were characterized by differential scanning calorimetry, X
      ray diffraction, Raman spectroscopy, and polarized microscopy. The results
      demonstrated that the glass transition temperature of the carrier polymers
      decreased as direct result of the surfactants in the extrudate, due to an
      increase in the chain mobility of polymers. A decrease in the melt viscosity was
      seen due to a plasticization of the polymer. The drug release profiles of the
      extruded solid dispersions containing intra granular surfactants were found to
      fit the dispersions with extra granularly added surfactants.

PMID- 16968660
TI  - Importance of intra-individual variation in tumour volume of hepatic colorectal
      metastases.
AB  - AIMS: The efficacy of surgical resection for multiple colorectal hepatic
      metastases (MCHM) has been controversial. We examined the survival of patients
      who received surgery for MCHM and examined the factors associated with survival.
      METHODS: A retrospective analysis was performed of 50 consecutive patients who
      received hepatic resections for MCHM, defined as four or more metastatic lesions
      of colorectal cancer. RESULTS: Overall survival after hepatic resection for MCHM
      was 48% at 3years and 43% at 5years (median survival, 22.3months). Multivariate
      analyses revealed that a coefficient of variation (CV) in volume of hepatic
      metastases in each individual patient above 1.8 (P=0.01, HR=4.08, 95% CI=1.33
      12.5) was the only poor prognostic factor after resection of MCHM. CONCLUSIONS: A
      CV in volume of hepatic metastases in each individual patient above 1.8 predicts
      poor survival after hepatectomy of MCHM. Thus, the CV in volume of hepatic
      metastases in each individual patient might be useful in planning the therapeutic
      strategy for patients with MCHM.

PMID- 16968661
TI  - Increasing the power for detecting impairment in older adults with the Faces
      subtest from Wechsler Memory Scale-III: an empirical trial.
AB  - Empirical studies have questioned the validity of the Faces subtest from the WMS
      III for detecting impairment in visual memory, particularly among the elderly. A
      recent examination of the test norms revealed a significant age related floor
      effect already emerging on Faces I (immediate recall), implying excessive
      difficulty in the acquisition phase among unimpaired older adults. The current
      study compared the concurrent validity of the Faces subtest with an alternative
      measure between 16 Alzheimer's patients and 16 controls. The alternative measure
      was designed to facilitate acquisition by reducing the sequence of item
      presentation. Other changes aimed at increasing the retrieval challenge,
      decreasing error due to guessing and standardizing the administration. Analyses
      converged to indicate that the alternative measure provided a considerably
      greater differentiation than the Faces subtest between Alzheimer's patients and
      controls. Steps for revising the Faces subtest are discussed.

PMID- 16968663
TI  - Speaking rate and fundamental frequency as speech cues to perceived age.
AB  - This study aimed to specify a set of acoustic cues fundamental to vocal aging and
      to establish their perceptual relevance, using acoustic analysis and perceptual
      testing. Three experiments were conducted to identify the perceptual correlates
      of the aging voice. The first experiment analyzed important voice parameters that
      signal a person's age for 16 older males and 14 younger males. In the second and
      third experiments, these acoustic patterns were systematically shifted through
      resynthesis to see if perceived age would be significantly influenced. In the
      second experiment, the older and younger male voices were resynthesized by
      manipulating speaking rate and fundamental frequency to shift the perceived age
      of the groups toward each other. In the third experiment, older and middle-aged
      male voices were resynthesized in a similar manner. In both perceptual studies,
      an age estimation task with naive listeners was used. The results of the first
      experiment showed that, in older speakers, sentence, word, and diphthong
      durations were all significantly longer and mean fundamental frequency was
      significantly higher than for the younger group. In the second experiment, only
      the manipulation of speaking rate resulted in a significant shift in perceived
      age, and it did so only for the older subjects. In the third experiment, a
      significant shift in age estimates was observed for the middle-aged, but not the
      older, voices when speaking rate was manipulated. The results of both perception
      tests suggest that speaking rate, but possibly not fundamental frequency, is a
      perceptually relevant cue to age in voice.

PMID- 16968662
TI  - The relation of education and gender on the attention items of the Mini-Mental
      State Examination in Spanish speaking Hispanic elders.
AB  - The Mini-Mental State Examination (MMSE) [Folstein, M. F., Folstein, S. E., &
      McHugh, P. R. (1975). Mini-Mental State: A practical method for grading the
      cognitive state of patients for the clinician. Journal of Psychiatric Research,
      12, 189-198] has frequently been challenged for its bias against individuals with
      lower levels of education and the use of scoring adjustments for lower
      educational levels has become standard practice [Ostrosky-Solis, F., Lopez
      Arango, G., & Ardila, A. (2000). Sensitivity and specificity of the Mini Mental
      State Examination in a Spanish-speaking population. Applied Neuropsychology, 7,
      25-31]. An additional source of concern is that original instructions specify
      that the "serial 7's" item may be replaced by an apparently less difficult
      "backwards spelling" task. This study compared the performance on these items and
      the effects for total scores on 102 unimpaired and 58 memory impaired elder
      Hispanic individuals (age 54-98), divided into 3 groups based on educational
      level (<7, 7-11, and >11 years of education). The effects of education and gender
      on the total MMSE scores were analyzed using the "serial 7's" and the "backwards
      spelling" items. For all the studied groups, MMSE scores were higher by an
      average of 1.5 points when using the "backwards spelling" task. Correlation
      between "serial 7's" and "backwards spelling" was a modest .37. Education had a
      significant effect on the MMSE scores in both the impaired and the unimpaired
      groups. After controlling for education, gender also explains a significant
      proportion of the variance of the results. The "backwards spelling" and "serial
      7's" items do not appear to be either equivalent in difficulty or to test the
      same abilities in the unimpaired and the impaired Hispanics elders tested in this
      study.

PMID- 16968664
TI  - Should singing activities be included in speech and voice therapy for prepubertal
      children?
AB  - Customarily, speaking and singing have tended to be regarded as two completely
      separate sets of behaviors in clinical and educational settings. The treatment of
      speech and voice disorders has focused on the client's speaking ability, as this
      is perceived to be the main vocal behavior of concern. However, according to a
      broader voice-science perspective, given that the same vocal structure is used
      for speaking and singing, it may be possible to include singing in speech and
      voice therapy. In this article, a theoretical framework is proposed that
      indicates possible benefits from the inclusion of singing in such therapeutic
      settings. Based on a literature review, it is demonstrated theoretically why
      singing activities can potentially be exploited in the treatment of prepubertal
      children suffering from speech and voice disorders. Based on this theoretical
      framework, implications for further empirical research and practice are
      suggested.

PMID- 16968665
TI  - Functional analysis of voice using simultaneous high-speed imaging and acoustic
      recordings.
AB  - We present a comprehensive, functional analysis of clinical voice data derived
      from both high-speed digital imaging (HSDI) of the larynx and simultaneously
      acquired acoustic recordings. The goals of this study are to: (1) correlate
      dynamic characteristics of the vocal folds derived from direct laryngeal imaging
      with indirectly acquired acoustic measurements; (2) define the advantages of
      using a combined imaging/acoustic approach for the analysis of voice condition;
      and (3) identify new quantitative measures to evaluate the regularity of the
      vocal fold vibration and the complexity of the vocal output -- these measures
      will be key to successful diagnosis of vocal abnormalities. Image- and acoustic
      based analyses are performed using an analytic phase plot approach previously
      introduced by our group (referred to as 'Nyquist' plot). Fast Fourier Transform
      (FFT) spectral analyses are performed on the same data for a comparison. Clinical
      HSDI and acoustic recordings from subjects having normal and specific voice
      pathologies, including muscular tension dysphonia (MTD) and recurrent respiratory
      papillomatosis (RRP) were analyzed using the Nyquist plot approach. The results
      of these analyses show that a combined imaging/acoustic analysis approach
      provides better characterization of the vibratory behavior of the vocal folds as
      it correlates with vocal output and pathology.

PMID- 16968666
TI  - Screening for abdominal aortic aneurysm: time for action.

PMID- 16968667
TI  - The occurrence of arterio-venous fistula during lower limb subintimal
      angioplasty: treatment and outcome.
AB  - OBJECTIVES: To describe our experience with iatrogenic arterio-venous fistula
      (AVF) occurring during lower limb subintimal angioplasty, their management and
      the final clinical, radiological outcome. DESIGN: Retrospective review of case
      series from two centres, from a computerised database over a period of five
      years. MATERIAL: Twelve patients whose lower limb subintimal angioplasty was
      complicated by Iatrogenic AVF. RESULTS: The Majority of AVF occurred at the
      popliteal trifurcation vessels. And the incidence of this complication in our
      case series was 0.8%. This was managed with a variety of techniques-Coil
      embolisation, balloon tamponade, alternative dissection and stent placement. In
      one patient, the fistula was left open intentionally. All twelve patients had a
      successful angioplasty. The overall technical success rate for AVF ablation was
      eighty percent. CONCLUSIONS: AVF is a potential complication of angioplasty. The
      majority can be managed by endovascular means during the angioplasty procedure
      with good technical success.

PMID- 16968668
TI  - Factors affecting patency of subintimal infrainguinal angioplasty in patients
      with critical lower limb ischemia.
AB  - BACKGROUND: Because subintimal angioplasty (SA) is a technique that can achieve
      recanalization of long arterial occlusions, it is considered an alternative to
      lower limb bypass operations. The aim of this prospective study was to identify
      the risk factors that affect patency of SA in patients suffering from critical
      limb ischemia (CLI). METHODS AND RESULTS: 51 consecutive infrainguinal SA were
      done in 46 patients suffered from CLI. The patients were followed-up with regular
      duplex scans up to 12 months post-intervention. Sex, atherosclerosis risk
      factors, and some technical details of the procedure (number of patent run-off
      vessels after the procedure, length and re-entry point of angioplasty) were
      examined as potential risk factors of patency, using survival analysis
      statistical techniques. The overall patency rate at 12 months post-intervention
      was 50%. According to Cox-regression analysis, the factors that affect patency
      were the number of run-off vessels and the length of occlusion. Patients with two
      or three run-off vessels had a hazard of occlusion of 0.30 (P = .027) compared to
      those who had one run-off vessel. The 12-months patency in patients with more
      than one run-off vessels was 81% vs. 25% in patients with one run-off vessel.
      Regarding the length of angioplasty, the hazard of reocclusion was 1.02 for every
      centimeter of occlusion (P = .049). CONCLUSIONS: The number of patent run-off
      crural vessels after the angioplasty and the length of occlusion are significant
      risk factors for reocclusion of infrainguinal SA in patients with CLI. Trying to
      recanalize more than one run-off vessels could raise the SA patency.

PMID- 16968669
TI  - Intranasal administration of adjuvant-combined recombinant influenza virus HA
      vaccine protects mice from the lethal H5N1 virus infection.
AB  - Attenuated recombinant H5N1 influenza virus was constructed to develop a safe
      H5N1 influenza vaccine. The immunogenicity and protective effect of the vaccine
      prepared from haemagglutinin-modified recombinant H5N1 influenza virus was
      evaluated in mice intranasally co-administered with cholera toxin B subunit
      containing a trace amount of holotoxin (CTB*), synthetic double-stranded RNA,
      poly (I:C) or chitin microparticles (CMP) as adjuvants. Intranasal administration
      of recombinant H5 HA split vaccine with CTB* or poly(I:C) and/or CMP elicited an
      immunological response with both anti-H5 HA IgA in the nasal wash and anti-H5 HA
      IgG antibody in the serum, and showed a protective against lethal H5N1 A/Hong
      Kong/483/97 (HK483) infection. We also demonstrated that intranasal co
      administration of antigen with both poly (I:C) and CMP enhanced the expression of
      Toll-like receptor (TLR) 3, TLR7 in the spleen. These results indicate that poly
      (I:C) and CMP are highly effective as mucosal adjuvants for use with the nasal
      H5N1 vaccine.

PMID- 16968670
TI  - HIV-1 Vpr induces G2 cell cycle arrest in fission yeast associated with Rad24/14
      3-3-dependent, Chk1/Cds1-independent Wee1 upregulation.
AB  - Viral protein R (Vpr), an accessory protein of human immunodeficiency virus type
      1 (HIV-1), induces the G2 cell cycle arrest in fission yeast for which host
      factors, such as Wee1 and Rad24, are required. Catalyzing the inhibitory
      phosphorylation of Cdc2, Wee1 is known to serve as a major regulator of G2/M
      transition in the eukaryotic cell cycle. It has been reported that the G2
      checkpoint induced by DNA damage or incomplete DNA replication is associated with
      phosphorylation and upregulation of Wee1 for which Chk1 and Cds1 kinase is
      required. In this study, we demonstrate that the G2 arrest induced by HIV-1 Vpr
      in fission yeast is also associated with increase in the phosphorylation and
      amount of Wee1, but in a Chk1/Cds1-independent manner. Rad24 and human 14-3-3
      appear to contribute to Vpr-induced G2 arrest by elevating the level of Wee1
      expression. It appears that Vpr could cause the G2 arrest through a mechanism
      similar to, but distinct from, the physiological G2 checkpoint controls. The
      results may provide useful insights into the mechanism by which HIV-1 Vpr causes
      the G2 arrest in eukaryotic cells. Vpr may also serve as a useful molecular tool
      for exploring novel cell cycle control mechanisms.

PMID- 16968671
TI  - Activation of mitochondrial-driven apoptosis in skeletal muscle cells is not
      mediated by reactive oxygen species production.
AB  - While the acquisition of apoptosis resistance is part of the differentiation
      program of skeletal muscle cells, differentiated muscle cells can undergo
      apoptosis in response to physiological or pathological stimuli. The generation of
      reactive oxygen species by mitochondria plays a major role in the control of
      apoptosis in many cell types. Indeed their involvement in controlling apoptosis
      in differentiated muscle cells, or in generating resistance to apoptosis remains
      unknown. Moreover, differentiated muscle cells specifically express the
      uncoupling protein-3, a mitochondrial protein potentially involved in controlling
      reactive oxygen species production. To study the role of mitochondrial reactive
      oxygen species in the control of apoptosis in skeletal muscle cells, L6E9
      myoblasts and myotubes were exposed to staurosporine, an inducer of apoptosis via
      mitochondrial pathways. Staurosporine activated apoptotic pathways (i.e. caspase
      3 and caspase-9) increasing reactive oxygen species in myoblasts and, to a minor
      extent, in myotubes. However, the increase in reactive oxygen species was not
      needed to induce apoptosis nor was it involved in the differential sensitization
      of myoblasts and myotubes to apoptosis. Moreover, expression of uncoupling
      protein-3 in myotubes did not affect reactive oxygen species production, although
      it produced a slight sensitization for staurosporine-induced apoptosis. Results
      indicate that apoptotic activation in skeletal muscle cells mainly involves
      reactive oxygen species-independent mechanisms and that mitochondrial uncoupling
      protein-3 is not protective either for reactive oxygen species production or for
      apoptotic activation in muscle cells.

PMID- 16968672
TI  - Photophysical studies of Merocyanine 540 dye in aqueous micellar dispersions of
      different surfactants and in different solvents.
AB  - The fluorescence spectra of Merocyanine 540 (MC 540), an anionic dye have been
      studied in aqueous solution of different nonionic surfactants. The results show
      the enhancement and red shift of fluorescence bands, indicating electron transfer
      from the surfactants to the excited dye. This is also supported by the
      photovoltage generation by the dye-surfactant systems in a photoelectrochemical
      cell. Possible mechanisms of the excited state interaction and photovoltage
      generation have been suggested. From the thermodynamic, spectrophotometric and
      photogalvanic results, it can be concluded that the electron donating abilities
      of the nonionic surfactants towards MC 540 are in the order: Tween 80
      approximately Tween 60>Tween 40>Tween 20>Triton X-100. The spectral studies (both
      absorption and fluorescence) of Merocyanine 540 have been carried out in solvents
      of varying polarities as well as in an aqueous micellar dispersions of nonionic
      surfactants. The Stokes shifts of the fluorescence from the absorption have been
      found to increase with increasing polarity of the solvents. An attempt has been
      made to ascertain the polarity of the microenvironment of Merocyanine 540 in the
      nonionic surfactant media from the photophysical characteristics of the dye in
      different solvents of known polarities.

PMID- 16968673
TI  - Electrochemiluminescence from successive electro- and chemo-oxidation of
      rifampicin and its application to the determination of rifampicin in
      pharmaceutical preparations and human urine.
AB  - A novel electrochemiluminescence (ECL) type was proposed based on successive
      electro- and chemo-oxidation of oxidable analyte, which was different from both
      annihilation and coreactant ECL types in mechanism. Rifampicin was used as a
      model compound. No any chemiluminescence (CL) was produced by either
      electrochemical oxidation or chemical oxidation of rifampicin in KH(2)PO(4)-
      Na(2)B(4)O(7) (pH 6.6) buffer-dodecyl trimethyl ammonium chloride (DTAC)
      solution. However, an ECL was observed by electrochemical oxidization of
      rifampicin in the same solution in the presence of oxidant such as dissolved
      oxygen, activated oxygen and potassium peroxydisulfate (K(2)S(2)O(8)). The ECL
      was attributed to electrochemical oxidation of rifampicin to form semiquinone
      free radical, and then subsequently chemical oxidation of the formed radical by
      oxidant to form excited state rifampicin quinone. The proposed ECL type
      introduced additional advantages such as high selectivity, simple and convenient
      operation, and effective avoidance of side reaction that often took place in
      homogenous CL reaction, and will open a novel application field. In addition,
      with the ECL in the presence of K(2)S(2)O(8) as oxidant, a flow injection ECL
      method for the determination of rifampicin was proposed. The ECL intensity was
      linear with rifampicin concentration in the range of 1.0 x 10(-7) to 4.0 x 10(-5)
      mol l(-1) and the limit of detection (s/n=3) was 3.9 x 10(-8) mol l(-1). The
      proposed method was applied to the determination of rifampicin in pharmaceutical
      preparations and human urine.

PMID- 16968674
TI  - Determination of carbaryl and its metabolite 1-naphthol in water samples by
      fluorescence spectrophotometer after anionic surfactant micelle-mediated
      extraction with sodium dodecylsulfate.
AB  - Anionic surfactant micelle-mediated extraction with sodium dodecylsulfate (SDS)
      was applied as preconcentration step prior to fluorescence spectrophotometer
      without further cleanup step. The obtained surfactant-rich phase was diluted to a
      fixed volume with water-miscible solvents. Carbaryl and its metabolite 1-naphthol
      were used as test compounds. The detection limits (LODs) of the method were in
      the microgram per liter area. Recoveries obtained from four real water samples
      ranged from 90.7 to 98.6%. Under the optimum experimental conditions, the method
      described showed a good precision, with relative standard deviations (R.S.D.) of
      less than 6%. According to the results, this approach reduced the viscidity of
      the surfactant-rich phase and made the combination of fluorescence
      spectrophotometer with anionic surfactant micelle-mediated extraction much
      easier.

PMID- 16968675
TI  - Sensitized phosphorescence studies of p-xylene+biacetyl system, an optical
      antenna.
AB  - p-Xylene sensitized biacetyl fluorescence and phosphorescence has been
      investigated and photosensitized phosphorescence lifetimes of biacetyl in the
      vapor phase has been determined. Attempts to detect the triplet of biacetyl by
      its absorption spectrum were unsuccessful, due to primarily, it is believed, to
      the low extinction coefficients of the triplet, and the low triplet
      concentrations produced by the optical pumping device at room temperature.

PMID- 16968676
TI  - Rapid detection of Norovirus based on an automated extraction protocol and a real
      time multiplexed single-step RT-PCR.
AB  - BACKGROUND: Molecular diagnosis of Norovirus infection can be a complex multistep
      process, which requires significant user intervention and expertise, and is not
      amenable to automation without extensive validation and optimization. OBJECTIVES:
      To develop a real-time multiplexed RT-PCR assay with automated sample preparation
      that requires only a single-step and a single-tube for reverse transcription,
      amplification, and detection while exceeding the sensitivity of conventional PCR
      for broad-spectrum Norovirus detection. STUDY DESIGN: Limit of detection was
      assessed against dilutions of clinical specimens. Fifty archived extractions were
      used to compare TaqMan sensitivity with either a separate RT using random primers
      or a single-step RT-PCR. The sensitivity of the novel assay was compared with
      conventional RT-PCR using 100 specimens from gastroenteritis cases. RESULTS:
      Automated extraction reduced RNA recovery by 0.5 logs compared to manual
      extraction but was more effective at removing PCR inhibitors from stool
      specimens. The optimized single-step real-time RT-PCR demonstrated no reduction
      in sensitivity. Together, the sensitivity of the novel assay was 19% higher than
      manual extraction with conventional RT-PCR. CONCLUSIONS: A semi-automated and
      simplified molecular diagnostic protocol for the rapid detection of Norovirus has
      been achieved. PCR inhibitors are present in human fecal specimens and cause a
      significant problem for Norovirus detection by RT-PCR.

PMID- 16968677
TI  - Caffeine delays replication fork progression and enhances UV-induced homologous
      recombination in Chinese hamster cell lines.
AB  - The ability to bypass DNA lesions encountered during replication is important in
      order to maintain cell viability and avoid genomic instability. Exposure of
      mammalian cells to UV-irradiation induces the formation of DNA lesions that stall
      replication forks. In order to restore replication, different bypass mechanisms
      are operating, previously named post-replication repair. Translesion DNA
      synthesis is performed by low-fidelity polymerases, which can replicate across
      damaged sites. The nature of lesions and of polymerases involved influences the
      resulting frequency of mutations. Homologous recombination represents an
      alternative pathway for the rescue of stalled replication forks. Caffeine has
      long been recognized to influence post-replication repair, although the mechanism
      is not identified. Here, we found that caffeine delays the progress of
      replication forks in UV-irradiated Chinese hamster cells. The length of this
      enhanced delay was similar in wild-type cells and in cell deficient in either
      homologous recombination or nucleotide excision repair. Furthermore, caffeine
      attenuated the frequency of UV-induced mutations in the hprt gene, whereas the
      frequency of recombination, monitored in this same gene, was enhanced. These
      observations indicate that in cells exposed to UV-light, caffeine inhibits the
      rescue of stalled replication forks by translesion DNA synthesis, thereby causing
      a switch to bypass via homologous recombination. The biological consequence of
      the former pathway is mutations, while the latter results in chromosomal
      aberrations.

PMID- 16968678
TI  - Determinants of offline processing of visual information for the control of
      reaching movements.
AB  - The authors investigated the use of visual feedback as a form of knowledge of
      results (KR) for the control of rapid (200-250 ms) reaching movements in 40
      participants. They compared endpoint accuracy and intraindividual variability of
      a full-vision group (FV) with those of no-vision groups provided with KR
      regarding (a) the endpoint in numerical form, (b) the endpoint in visual form, or
      (c) the endpoint and the trajectory in visual form (DEL). The FV group was more
      accurate and less variable than were the no-vision groups, and the analysis of
      limb trajectory variability indicated that their superior performance resulted
      primarily from better movement planning rather than from online visual processes.
      The FV group outperformed the DEL group even though both groups were obtaining
      the same amount of spatial visual information from every movement. That finding
      suggests that the effectiveness with which visual feedback is processed offline
      is not a simple function of the amount of visual information available, but
      depends on how that information is presented.

PMID- 16968679
TI  - Chronometric comparison of actual and imaged complex movement patterns.
AB  - The authors' aim in this study was to consider the functional equivalence of
      internal imagery, external imagery, and action execution. Sixteen elite gymnasts
      imaged and performed a complex gymnastic vault. Ten performers imaged from an
      internal perspective, and 6 used an external perspective. Although the results
      revealed that the time to image the entire motor task did not significantly
      differ from the time required to physically perform it, irrespective of the
      imagery perspective used, the temporal organization of the action was different
      within the imagery conditions than it was in the physical condition. The results
      do not provide support for the principle of temporal functional equivalence. The
      authors discuss the results in light of recent findings from the cognitive
      neuroscience and psychology literatures.

PMID- 16968681
TI  - Scaling a motor skill through observation and practice.
AB  - The authors examined the proposal that a motor skill is scaled through physical
      practice and not through observation of a model. In 4 groups, participants (N =
      32) did or did not imitate a model bowling a ball to a target 8 m away. In an
      assessment phase, those groups did or did not observe the same model bowling a
      ball to a target 4 m away. Participants who viewed a model in the assessment
      phase were more accurate and consistent in terms of bowling accuracy than were
      those who did not. Their shoulder and wrist velocity profiles were more similar
      to those of the 4-m model than were those of the no-model group. Participants who
      had previous practice and viewed a demonstration were more accurate at scaling
      the wrist of the bowling arm. Observing a demonstration facilitates the
      acquisition of control-related features of a movement. Furthermore, early
      acquisition of coordination aids the use of velocity information for scaling the
      endpoint of the primary effector.

PMID- 16968680
TI  - Walking and running on the circular treadmill: transition speed and podokinetic
      aftereffects.
AB  - The author compared 10 participants' self-selected walk-to-run transition speeds
      on a standard treadmill with those on a circular treadmill. The speed of the
      outer limb at walk-to-run transition on the circular treadmill and on the
      standard treadmill were very similar. Adaptive aftereffects from running and
      walking on the circular treadmill were also similar. When asked to step in place
      without vision, all participants inadvertently turned in circles following
      walking or running on the treadmill. The results of the present study suggest
      that the mechanisms controlling walk-to-run transitions are similar for the
      standard and circular treadmills and demonstrate the robust generalizability of
      locomotor aftereffects from running to walking. Adaptive control of speed, form,
      and direction may therefore share similar mechanisms for walking and running.

PMID- 16968682
TI  - Changes in step variability of new walkers with typical development and with Down
      syndrome.
AB  - Models of human gait are based on adult locomotion. C. E. Bauby and A. D. Kuo
      (2000) proposed that adults rely on passive mechanisms at the spinal level to
      control motion in the anteroposterior direction and rely on direct monitoring of
      postural control in the lateral direction. The authors' purpose in this study was
      to determine if that model applies to control at the onset of walking in
      typically developing toddlers (n = 9) and in toddlers with Down syndrome (n = 6).
      Their longitudinal data suggested that toddlers control gait in a distinctly
      different manner than adults do. An adult pattern of control emerges with
      experience. In addition, the effect of experience on the emergence of that
      pattern is magnified by task-specific early intervention. The present data
      support the emergence and discovery of efficient patterns of control in this
      fundamental human behavior.

PMID- 16968683
TI  - Growing older does not always mean moving slower: examining aging and the
      saccadic motor system.
AB  - Although humans typically move more slowly as they age, one exception may be the
      saccadic motor system. To fully determine whether the execution of saccades is
      affected by age, the authors examined detailed kinematics of vertical and
      horizontal saccades across a range of saccadic amplitudes (4 degrees, 8 degrees,
      and 12 degrees). Ten younger and 20 older adults participated in each experiment.
      Whereas in the 1st experiment, the authors assessed volitionally generated
      saccades, in the 2nd experiment, they evaluated reflexively generated saccades.
      The results of those experiments showed that the saccadic motor system is
      relatively impervious to the effects of aging; in fact, the differences between
      vertical and horizontal saccades were more evident than were differences between
      saccades produced by younger and older adults. The authors discuss possible
      reasons for that relative resistance to aging.

PMID- 16968684
TI  - Effects of movement frequency and joint kinetics on the joint coordination
      underlying bimanual circle drawing.
AB  - Ten healthy participants performed bimanual symmetric and asymmetric circle
      drawing at 4 frequencies. The authors partitioned the variance of the joint
      configuration across repetitions into 1 component representing equivalent joint
      configurations with respect to achieving stability of the mean hand path (i.e.,
      goal-equivalent variance, GEV) and 1 component leading to a variable hand path
      (non-goal-equivalent variance, NGEV) across cycles. Higher frequencies led to
      increased NGEV related to control of the nondominant hand and to the relative
      position and orientation between the hands during asymmetric drawing. The results
      were related to differences in muscle and interaction moments between the arms,
      and they suggest a possible relationship between the ability to use
      intersegmental forces and the stability of interlimb synergy.

PMID- 16968685
TI  - Research methods of inquiry.
AB  - Incidents of significant consequence that create surge may require special
      research methods to provide reliable, generalizable results. This report was
      constructed through a process of literature review, expert panel discussion at
      the journal's consensus conference, and iterative development. Traditional
      clinical research methods that are well accepted in medicine are exceptionally
      difficult to use for surge incidents because the incidents are very difficult to
      reliably predict, the consequences vary widely, human behaviors are heterogeneous
      in response to incidents, and temporal conditions prioritize limited resources to
      response, rather than data collection. Current literature on surge research
      methods has found some degree of reliability and generalizability in case
      control, postincident survey methods, and ethnographical designs. Novel methods
      that show promise for studying surge include carefully validated simulation
      experiments and survey methods that produce validated results from representative
      populations. Methodologists and research scientists should consider quasi
      experimental designs and case-control studies in areas with recurrent high
      consequence incidents (e.g., earthquakes and hurricanes). Specialists that need
      to be well represented in areas of research include emergency physicians and
      critical care physicians, simulation engineers, cost economists, sociobehavioral
      methodologists, and others.

PMID- 16968686
TI  - The science of surge: an all-hazard approach is critical to improving public
      health preparedness.

PMID- 16968687
TI  - The science of surge: detection and situational awareness.
AB  - As part of the broader "science of surge" consensus initiative sponsored by
      Academic Emergency Medicine, this report addresses the issues of detection and
      situational awareness as they relate to surge in the practice of emergency
      medicine. The purpose of this report, and the breakout group that contributed to
      its content, was to provide emergency physicians and other stakeholders in the
      emergency medicine community a sense of direction as they plan, prepare for, and
      respond to surge in their practice.

PMID- 16968688
TI  - Surge capacity for healthcare systems: a conceptual framework.
AB  - This report reflects the proceedings of a breakout session, "Surge Capacity:
      Defining Concepts," at the 2006 Academic Emergency Medicine Consensus Conference,
      "Science of Surge Capacity." Although there are several general descriptions of
      surge capacity in the literature, there is no universally accepted standard
      definition specifying the various components. Thus, the objectives of this
      breakout session were to better delineate the components of surge capacity and to
      outline the key considerations when planning for surge capacity. Participants
      were from diverse backgrounds and included academic and community emergency
      physicians, economists, hospital administrators, and experts in mathematical
      modeling. Three essential components of surge capacity were identified: staff,
      stuff, and structure. The focus on enhancing surge capacity during a catastrophic
      event will be to increase patient-care capacity, rather than on increasing
      things, such as beds and medical supplies. Although there are similarities
      between daily surge and disaster surge, during a disaster, the goal shifts from
      the day-to-day operational focus on optimizing outcomes for the individual
      patient to optimizing those for a population. Other key considerations in
      defining surge capacity include psychosocial behavioral issues, convergent
      volunteerism, the need for special expertise and supplies, development of a
      standard of care appropriate for a specific situation, and standardization of a
      universal metric for surge capacity.

PMID- 16968689
TI  - Preventing incapacity in people with musculoskeletal disorders.
AB  - Musculoskeletal disorders are among the most common causes of sickness absence,
      long-term incapacity for work and ill-health retirement. The number of Incapacity
      Benefit (IB) recipients in the United Kingdom has trebled since 1979, despite
      improvement in objective measures of health. Most of the trend is in non-specific
      conditions (largely subjective complaints, often with little objective pathology
      or impairment). Understanding incapacity requires a biopsychosocial model that
      addresses all the physical, psychological and social factors involved in human
      illness and disability. Rehabilitation should be directed to overcome
      biopsychosocial obstacles to recovery and return to work. These principles are
      fundamental to better clinical and occupational management and minimizing
      incapacity. Sickness absence and incapacity from non-specific musculoskeletal
      conditions could be reduced by 33-50%, but that depends on getting all
      stakeholders onside and a fundamental shift in thinking about these conditions-in
      health care, in the workplace and in society.

PMID- 16968690
TI  - Fanconi's anaemia and related bone marrow failure syndromes.
AB  - The inherited bone marrow (BM) failure syndromes are a heterogeneous group of
      disorders characterized by BM failure, usually in association with one or more
      somatic abnormalities. The BM failure may present at birth or at a variable time
      thereafter including in adulthood in some cases. Over the last decade, there have
      been significant advances in the genetics of these syndromes particularly
      Fanconi's anaemia (FA) and dyskeratosis congenita (DC). These advances are
      beginning to provide a better understanding of normal haemopoiesis and of the
      pathophysiology of some cases of idiopathic aplastic anaemia (AA). They have also
      provided important insights into some aspects of DNA repair (FA/BRCA pathway) and
      telomere maintenance (DC-related genes), two pathways critical in the maintenance
      of genomic stability. These advances are already facilitating better diagnosis of
      patients with these disorders. It is hoped that they will also form the basis for
      developing new treatments.

PMID- 16968691
TI  - Allogeneic haematopoietic stem cell transplantation: current status and future
      outlook.
AB  - Allogeneic haematopoietic stem cell transplantation (allo-SCT) is an established
      treatment of haematological malignancies and other immunohaematopoietic
      disorders. The use of unrelated donors and cord blood (CB) grafts has increased
      the possibilities of finding a donor, and results are approaching those after
      sibling donor transplants. The use of peripheral blood stem cells (PBSCs),
      instead of bone marrow, results in faster engraftment and increased risk of
      chronic graft-versus-host disease (GVHD). High-dose myeloablative (MA)
      conditioning is recently challenged by reduced-intensity conditioning (RIC) for
      older patients and those with comorbidity. Better diagnostic tools and novel anti
      microbial drugs have reduced morbidity and mortality from infections. A major
      problem is disease relapse. Early detection of minimal residual disease or
      recurrent recipient haematopoietic cells allows early intervention with
      immunotherapy. Donor lymphocyte infusions (DLIs) have not only an anti-leukaemic
      effect but also an anti-tumour effect against a variety of solid organ tumours.
      New indications such as metastatic solid tumours are investigated. Mesenchymal
      stem cells (MSC) may enhance engraftment and have immunomodulatory effects.

PMID- 16968692
TI  - Atypical haemolytic uraemic syndrome.
AB  - The haemolytic uraemic syndrome (HUS) is characterized by the triad of
      thrombocytopenia, microangiopathic haemolytic anaemia and acute renal failure.
      HUS may be classified as either diarrhoeal-associated or non-diarrhoeal/atypical
      (aHUS). aHUS has recently been shown to be a disease of complement dysregulation,
      with 50% of cases involving the complement regulatory genes, factor H (CFH),
      membrane cofactor protein (MCP; CD46), and factor I (IF). However, incomplete
      penetrance of mutations in each of these genes is reported. This suggests that a
      precipitating event or trigger is required to unmask the complement regulatory
      deficiency. The reported precipitating events predominantly cause endothelial
      injury. Discovery of these mutations has revealed important genotype-phenotype
      correlations. MCP-HUS has a better prognosis and a better outcome after
      transplantation than either CFH-HUS or IF-HUS.

PMID- 16968693
TI  - Prolyl-tRNA(Pro) in the A-site of SecM-arrested ribosomes inhibits the
      recruitment of transfer-messenger RNA.
AB  - Translational pausing can lead to cleavage of the A-site codon and facilitate
      recruitment of the transfer-messenger RNA (tmRNA) (SsrA) quality control system
      to distressed ribosomes. We asked whether aminoacyl-tRNA binding site (A-site)
      mRNA cleavage occurs during regulatory translational pausing using the
      Escherichia coli SecM-mediated ribosome arrest as a model. We find that SecM
      ribosome arrest does not elicit efficient A-site cleavage, but instead allows
      degradation of downstream mRNA to the 3'-edge of the arrested ribosome.
      Characterization of SecM-arrested ribosomes shows the nascent peptide is
      covalently linked via glycine 165 to tRNA(3Gly) in the peptidyl-tRNA binding
      site, and prolyl-tRNA(2Pro) is bound to the A-site. Although A-site-cleaved mRNAs
      were not detected, tmRNA-mediated ssrA tagging after SecM glycine 165 was
      observed. This tmRNA activity results from sequestration of prolyl-tRNA(2Pro) on
      overexpressed SecM-arrested ribosomes, which produces a second population of
      stalled ribosomes with unoccupied A-sites. Indeed, compensatory overexpression of
      tRNA(2Pro) readily inhibits ssrA tagging after glycine 165, but has no effect on
      the duration of SecM ribosome arrest. We conclude that, under physiological
      conditions, the architecture of SecM-arrested ribosomes allows regulated
      translational pausing without interference from A-site cleavage or tmRNA
      activities. Moreover, it seems likely that A-site mRNA cleavage is generally
      avoided or inhibited during regulated ribosome pauses.

PMID- 16968694
TI  - Ras triggers ataxia-telangiectasia-mutated and Rad-3-related activation and
      apoptosis through sustained mitogenic signaling.
AB  - Genetic evidence indicates that Ras plays a critical role in the initiation and
      progression of human thyroid tumors. Paradoxically, acute expression of activated
      Ras in normal rat thyroid cells induced deregulated cell cycle progression and
      apoptosis. We investigated whether cell cycle progression was required for Ras
      stimulated apoptosis. Ras increased CDK-2 activity following its introduction
      into quiescent cells. Apoptotic cells exhibited a sustained increase in CDK-2
      activity, accompanied by the loss of CDK-2-associated p27. Blockade of Ras
      induced CDK-2 activity and S phase entry via overexpression of p27 inhibited
      apoptosis. Inactivation of the retinoblastoma protein in quiescent cells through
      expression of HPV-E7 stimulated cell cycle progression and apoptosis, indicating
      that deregulated cell cycle progression is sufficient to induce apoptosis. Ras
      failed to induce G1 phase growth arrest in normal rat thyroid cells. Rather, Ras
      expressing thyroid cells progressed into S and G2 phases and evoked a checkpoint
      response characterized by the activation of ATR. Ras-stimulated ATR activity, as
      evidenced by Chk1 and p53 phosphorylation, was blocked by p27, suggesting that
      cell cycle progression triggers checkpoint activation, likely as a consequence of
      replication stress. These data reveal that Ras is capable of inducing a DNA
      damage response with characteristics similar to those reported in precancerous
      lesions. Our findings also suggest that the frequent mutational activation of Ras
      in thyroid tumors reflects the ability of Ras-expressing cells to bypass
      checkpoints and evade apoptosis rather than to simply increase proliferative
      potential.

PMID- 16968695
TI  - Control of phospholipid synthesis by phosphorylation of the yeast lipin
      Pah1p/Smp2p Mg2+-dependent phosphatidate phosphatase.
AB  - Phosphorylation of the conserved lipin Pah1p/Smp2p in Saccharomyces cerevisiae
      was previously shown to control transcription of phospholipid biosynthetic genes
      and nuclear structure by regulating the amount of membrane present at the nuclear
      envelope (Santos-Rosa, H., Leung, J., Grimsey, N., Peak-Chew, S., and
      Siniossoglou, S. (2005) EMBO J. 24, 1931-1941). A recent report identified Pah1p
      as a Mg2+-dependent phosphatidate (PA) phosphatase that regulates de novo lipid
      synthesis (Han G.-S., Wu, W. I., and Carman, G. M. (2006) J. Biol. Chem. 281,
      9210-9218). In this work we use a combination of mass spectrometry and systematic
      mutagenesis to identify seven Ser/Thr-Pro motifs within Pah1p that are
      phosphorylated in vivo. We show that phosphorylation on these sites is required
      for the efficient transcriptional derepression of key enzymes involved in
      phospholipid biosynthesis. The phosphorylation-deficient Pah1p exhibits higher PA
      phosphatase-specific activity than the wild-type Pah1p, indicating that
      phosphorylation of Pah1p controls PA production. Opi1p is a transcriptional
      repressor of phospholipid biosynthetic genes, responding to PA levels. Genetic
      analysis suggests that Pah1p regulates transcription of these genes through both
      Opi1p-dependent and -independent mechanisms. We also provide evidence that
      derepression of phospholipid biosynthetic genes is not sufficient to induce the
      nuclear membrane expansion shown in the pah1delta cells.

PMID- 16968696
TI  - Functional genomic and metabolic studies of the adaptations of a prominent adult
      human gut symbiont, Bacteroides thetaiotaomicron, to the suckling period.
AB  - The adult human gut microbiota is dominated by two divisions of Bacteria, the
      Bacteroidetes and the Firmicutes. Assembly of this community begins at birth
      through processes that remain largely undefined. In this report, we examine the
      adaptations of Bacteroides thetaiotaomicron, a prominent member of the adult
      distal intestinal microbiota, during the suckling and weaning periods. Germ-free
      NMRI mice were colonized at birth from their gnotobiotic mothers, who harbored
      this anaerobic Gram-negative saccharolytic bacterium. B. thetaiotaomicron was
      then harvested from the ceca of these hosts during the suckling period (postnatal
      day 17) and after weaning (postnatal day 30). Whole genome transcriptional
      profiles were obtained at these two time points using custom B. thetaiotaomicron
      GeneChips. Transcriptome-based in silico reconstructions of bacterial metabolism
      and gas chromatography-mass spectrometry and biochemical assays of carbohydrate
      utilization in vivo indicated that in the suckling gut B. thetaiotaomicron
      prefers host-derived polysaccharides, as well as mono- and oligosaccharides
      present in mother's milk. After weaning, B. thetaiotaomicron expands its
      metabolism to exploit abundant, plant-derived dietary polysaccharides. The
      bacterium's responses to postnatal alterations in its nutrient landscape involve
      expression of gene clusters encoding environmental sensors, outer membrane
      proteins involved in binding and import of glycans, and glycoside hydrolases.
      These expression changes are interpreted in light of a phylogenetic analysis that
      revealed unique expansions of related polysaccharide utilization loci in three
      human alimentary tract-associated Bacteroidetes, expansions that likely reflect
      the evolutionary adaptations of these species to different nutrient niches.

PMID- 16968698
TI  - Identification of a DOCK180-related guanine nucleotide exchange factor that is
      capable of mediating a positive feedback activation of Cdc42.
AB  - Cdc42, a member of the Rho subfamily of small GTPases, influences a wide range of
      activities including the establishment of cell polarity, migration, and the
      regulation of cell growth and differentiation. Here we describe the
      identification of an approximately 220-kDa protein that formed a stable complex
      with activated forms of Cdc42 and thereby showed characteristics of a downstream
      target/effector for this GTPase. However, molecular cloning of the cDNA encoding
      this protein (p220) revealed that it was highly related to Zizimin-1 and
      identical in sequence to a gene product in the data base designated DOCK11, which
      are members of the DOCK180 family of guanine nucleotide exchange factors (GEFs)
      for Cdc42 and Rac. Biochemical characterization shows that p220 is a specific GEF
      for Cdc42, with the GEF activity originating from its DHR2 (for DOCK homology
      region 2) domain. Nucleotide-depleted Cdc42 forms a stable complex with the DHR2
      domain, whereas the binding of activated Cdc42 requires both the DHR2 domain and
      residues 66-126 within the amino-terminal portion of p220. Moreover, the full
      length protein shows markedly higher GEF activity than the isolated DHR2 domain,
      whereas removal of the amino-terminal 126 amino acids necessary for binding
      activated Cdc42 dramatically diminishes the activity. These and other results
      point to activated Cdc42 providing a positive feedback regulation of the GEF
      activity of p220. Thus, we refer to p220/DOCK11 as activated Cdc42-associated
      GEF, befitting its functional activity.

PMID- 16968697
TI  - Biochemical, molecular, and functional characterization of PISCF-allatostatin, a
      regulator of juvenile hormone biosynthesis in the mosquito Aedes aegypti.
AB  - Aedes aegypti PISCF-allatostatin or allatostatin-C (Ae-AS-C) was isolated using a
      combination of high performance liquid chromatography and enzyme-linked
      immunosorbent assay (ELISA). The matrix-assisted laser desorption/ionization time
      of-flight (TOF) mass spectrum of positive ELISA fractions revealed a molecular
      mass of 1919.0 Da, in agreement with the sequence qIRYRQCYFNPISCF, with bridged
      cysteines. This sequence was confirmed by matrix-assisted laser
      desorption/ionization tandem TOF/TOF mass spectrometry analysis. The
      corresponding Ae-AS-C cDNA was amplified by PCR, and the sequence of the peptide
      was confirmed. An in vitro radiochemical assay was used to study the inhibitory
      effect of synthetic Ae-AS-C on juvenile hormone biosynthesis by the isolated
      corpora allata (CA) of adult female A. aegypti. The inhibitory action of
      synthetic Ae-AS-C was dose-dependent; with a maximum at 10(-9) m. Ae-AS-C showed
      no inhibitory activity in the presence of farnesoic acid, an immediate precursor
      of juvenile hormone, indicating that the Ae-AS-C target is located before the
      formation of farnesoic acid in the pathway. The sensitivity of the CA to
      inhibition by Ae-AS-C in the in vitro assay varied during the adult life; the CA
      was most sensitive during periods of low synthetic activity. In addition, the
      levels of Ae-AS-C in the brain were studied using ELISA and reached a maximum at
      3 days after eclosion. These studies suggest that Ae-AS-C is an important
      regulator of CA activity in A. aegypti.

PMID- 16968699
TI  - Role of RacC for the regulation of WASP and phosphatidylinositol 3-kinase during
      chemotaxis of Dictyostelium.
AB  - WASP family proteins are key players for connecting multiple signaling pathways
      to F-actin polymerization. To dissect the highly integrated signaling pathways
      controlling WASP activity, we identified a Rac protein that binds to the GTPase
      binding domain of WASP. Using two-hybrid and FRET-based functional assays, we
      identified RacC as a major regulator of WASP. RacC stimulates F-actin assembly in
      cell-free systems in a WASP-dependent manner. A FRET-based microscopy approach
      showed local activation of RacC at the leading edge of chemotaxing cells. Cells
      overexpressing RacC exhibit a significant increase in the level of F-actin
      polymerization upon cAMP stimulation, which can be blocked by a
      phosphatidylinositol (PI) 3-kinase inhibitor. Membrane translocation of PI 3
      kinase and PI 3,4,5-trisphosphate reporter is absent in racC null cells. Cells
      overexpressing dominant negative RacC mutants and racC null cells move at a
      significantly slower speed and show a poor directionality during chemotaxis. Our
      results suggest that RacC plays an important role in PI 3-kinase activation and
      WASP activation for dynamic regulation of F-actin assembly during Dictyostelium
      chemotaxis.

PMID- 16968700
TI  - Identification of a novel apical sorting motif and mechanism of targeting of the
      M2 muscarinic acetylcholine receptor.
AB  - Previous studies have shown that the M2 receptor is localized at steady state to
      the apical domain in Madin-Darby canine kidney (MDCK) epithelial cells. In this
      study, we identify the molecular determinants governing the localization and the
      route of apical delivery of the M2 receptor. First, by confocal analysis of a
      transiently transfected glycosylation mutant in which the three putative
      glycosylation sites were mutated, we determined that N-glycans are not necessary
      for the apical targeting of the M2 receptor. Next, using a chimeric receptor
      strategy, we found that two independent sequences within the M2 third
      intracellular loop can confer apical targeting to the basolaterally targeted M4
      receptor, Val270-Lys280 and Lys280-Ser350. Experiments using Triton X-100
      extraction followed by OptiPrep density gradient centrifugation and cholera toxin
      beta-subunit-induced patching demonstrate that apical targeting is not because of
      association with lipid rafts. 35S-Metabolic labeling experiments with domain
      specific surface biotinylation as well as immunocytochemical analysis of the time
      course of surface appearance of newly transfected confluent MDCK cells expressing
      FLAG-M2-GFP demonstrate that the M2 receptor achieves its apical localization
      after first appearing on the basolateral domain. Domain-specific application of
      tannic acid of newly transfected cells indicates that initial basolateral plasma
      membrane expression is required for subsequent apical localization. This is the
      first demonstration that a G-protein-coupled receptor achieves its apical
      localization in MDCK cells via transcytosis.

PMID- 16968701
TI  - Functional importance of the interhelical hydrogen bond between Thr204 and Tyr174
      of sensory rhodopsin II and its alteration during the signaling process.
AB  - Sensory rhodopsin II (SRII), a receptor for negative phototaxis in haloarchaea,
      transmits light signals through changes in protein-protein interaction with its
      transducer HtrII. Light-induced structural changes throughout the SRII-HtrII
      interface, which spans the periplasmic region, membrane-embedded domains, and
      cytoplasmic domains near the membrane, have been identified by several studies.
      Here we demonstrate by site-specific mutagenesis and analysis of phototaxis
      behavior that two residues in SRII near the membrane-embedded interface (Tyr174
      on helix F and Thr204 on helix G) are essential for signaling by the SRII-HtrII
      complex. These residues, which are the first in SRII shown to be required for
      phototaxis function, provide biological significance to the previous observation
      that the hydrogen bond between them is strengthened upon the formation of the
      earliest SRII photointermediate (SRII(K)) only when SRII is complexed with HtrII.
      Here we report frequency changes of the S-H stretch of a cysteine substituted for
      SRII Thr204 in the signaling state intermediates of the SRII photocycle, as well
      as an influence of HtrII on the hydrogen bond strength, supporting a direct role
      of the hydrogen bond in SRII-HtrII signal relay chemistry. Our results suggest
      that the light signal is transmitted to HtrII from the energized interhelical
      hydrogen bond between Thr204 and Tyr174, which is located at both the retinal
      chromophore pocket and in helices F and G that form the membrane-embedded
      interaction surface to the signal-bearing second transmembrane helix of HtrII.
      The results argue for a critical process in signal relay occurring at this
      membrane interfacial region of the complex.

PMID- 16968702
TI  - Hsp90 functions in the targeting and outer membrane translocation steps of Tom70
      mediated mitochondrial import.
AB  - The Tom70 import receptor on the mitochondrial outer membrane specifically
      recognizes Hsp90 and Hsc70, a critical step for the import of mitochondrial
      preproteins, the targeting of which depends on these cytosolic chaperones. To
      analyze the role of Hsp90 in mitochondrial import, the effects of the Hsp90
      inhibitors geldanamycin and novobiocin were compared. Geldanamycin occludes the N
      terminal ATP-binding site of Hsp90, whereas novobiocin targets the C-terminal
      region of the chaperone. Here, novobiocin was found to inhibit preprotein import
      and, in particular, targeting to the purified cytosolic fragment of Tom70. Hsp90
      cross-linking to preprotein and coprecipitation of Hsp90 with Tom70 were both
      impaired by novobiocin. Overall, novobiocin treatment increased preprotein
      aggregation, contributing to reduced import competence. In contrast, geldanamycin
      had no apparent effect on preprotein interactions with Hsp90, formation of
      preprotein-chaperone complexes, Hsp90 docking onto Tom70, or preprotein
      association with the outer membrane. Instead, geldanamycin impaired formation of
      preprotein import intermediates at the outer membrane. This suggests a novel
      active role for Hsp90 in import steps subsequent to Tom70 targeting. Our results
      outline the mechanisms of Hsp90 function in preprotein targeting and transport.

PMID- 16968703
TI  - Gonadotropin-regulated testicular RNA helicase (GRTH/Ddx25) is a transport
      protein involved in gene-specific mRNA export and protein translation during
      spermatogenesis.
AB  - Gonadotropin-regulated testicular RNA helicase (GRTH/Ddx25), a member of the DEAD
      box protein family, is essential for completion of spermatogenesis. GRTH is
      present in the cytoplasm and nucleus of meiotic spermatocytes and round
      spermatids and functions as a component of mRNP particles, implicating its post
      transcriptional regulatory roles in germ cells. In this study, GRTH antibodies
      specific to N- or C-terminal sequences showed differential subcellular expression
      of GRTH 56- and 61-kDa species in nucleus and cytoplasm, respectively, of rodent
      testis and transfected COS1 cells. The 56-kDa nuclear species interacted with
      CRM1 and participated in mRNA transport. The phosphorylated cytoplasmic 61-kDa
      species was associated with polyribosomes. Confocal studies on COS-1 cells showed
      that GRTH-GFP was retained in the nucleus by treatment with a RNA polymerase
      inhibitor or the nuclear protein export inhibitor. This indicated that GRTH is a
      shuttling protein associated with RNA export. The N-terminal leucine-rich region
      (61-74 amino acids) was identified as the nuclear export signal that participated
      in CRM1-dependent nuclear export pathway. Deletion analysis identified a 14-amino
      acid GRTH sequence (100-114 amino acids) as a nuclear localization signal. GRTH
      selectively regulated the translation of specific genes including histone 4 and
      HMG2 in germ cells. In addition, GRTH participated in the nuclear export of RNA
      messages (PGK2, tACE, and TP2) in a gene-specific manner. These studies strongly
      indicate that the mammalian GRTH/Ddx25 gene is a multifunctional RNA helicase
      that is an essential regulator of sperm maturation.

PMID- 16968704
TI  - An unorthodox bacteriophytochrome from Rhodobacter sphaeroides involved in
      turnover of the second messenger c-di-GMP.
AB  - Bacteriophytochromes are bacterial photoreceptors that sense red/far red light
      using the biliverdin chromophore. Most bacteriophytochromes work as
      photoactivated protein kinases. The Rhodobacter sphaeroides bacteriophytochrome
      BphG1 is unconventional in that it has GGDEF and EAL output domains, which are
      involved, respectively, in synthesis (diguanylate cyclase) and degradation
      (phosphodiesterase) of the bacterial second messenger c-di-GMP. The GGDEF-EAL
      proteins studied to date displayed either diguanylate cyclase or
      phosphodiesterase activity but not both. To elucidate the function of BphG1, the
      holoprotein was purified from an Escherichia coli overexpression system designed
      to produce biliverdin. The holoprotein contained covalently bound biliverdin and
      interconverted between the red (dark) and far red (light-activated) forms. BphG1
      had c-di-GMP-specific phosphodiesterase activity. Unexpectedly for a photochromic
      protein, this activity was essentially light-independent. BphG1 expressed in E.
      coli was found to undergo partial cleavage into two species. The smaller species
      was identified as the EAL domain of BphG1. It possessed c-di-GMP
      phosphodiesterase activity. Surprisingly, the larger species lacking EAL
      possessed diguanylate cyclase activity, which was dependent on biliverdin and
      strongly activated by light. BphG1 therefore is the first phytochrome with a non
      kinase photoactivated enzymatic activity. This shows that the photosensory
      modules of phytochromes can transmit light signals to various outputs. BphG1 is
      potentially the first "bifunctional" enzyme capable of both c-di-GMP synthesis
      and hydrolysis. A model for the regulation of the "opposite" activities of BphG1
      is presented.

PMID- 16968705
TI  - Specific epitopes of domains II and III of Bacillus thuringiensis Cry1Ab toxin
      involved in the sequential interaction with cadherin and aminopeptidase-N
      receptors in Manduca sexta.
AB  - The Bacillus thuringiensis Cry toxins are specific to different insects. In
      Manduca sexta cadherin (Bt-R1) and aminopeptidase-N (APN) proteins are recognized
      as Cry1A receptors. Previous work showed that Cry1Ab binds to Bt-R1 promoting the
      formation of a pre-pore oligomer that binds to APN leading to membrane insertion.
      In this work we characterized the binding epitopes involved in the sequential
      interaction of Cry1Ab with Bt-R1 and APN. A Cry1Ab immune M13 phage repertoire
      was constructed using antibody gene transcripts of bone marrow or spleen from a
      rabbit immunized with Cry1Ab. We identified antibodies that recognize domain II
      loop 3 (scFvL3-3) or beta16-beta22 (scFvM22) in domain III. Enzyme-linked
      immunosorbent assay and toxin overlay binding competition assays in the presence
      of scFvL3-3, scFvM22, or synthetic peptides showed that domain II loop 3 is an
      important epitope for interaction with Bt-R1 receptor, whereas domain III beta16
      is involved in the interaction with APN. Both scFvL3-3 and scFvM22 lowered the
      toxicity of Cry1Ab to M. sexta larvae indicating that interaction with both
      receptors is important for in vivo toxicity. scFvL3-3 and anti-loop2 scFv
      (scFv73) promoted the formation of the pre-pore oligomer in contrast to scFvM22.
      In addition, scFvL3-3 and scFv73 preferentially recognized the monomeric toxin
      rather than the pre-pore suggesting a conformational change in domain II loops
      upon oligomerization. These results indicate for the first time that both
      receptor molecules participate in Cry1Ab toxin action in vivo: first the
      monomeric toxin binds to Bt-R1 through loops 2 and 3 of domain II promoting the
      formation of the pre-pore inducing some structural changes, then the pre-pore
      interacts with APN through beta-16 of domain III promoting membrane insertion and
      cell death.

PMID- 16968706
TI  - Triad3A regulates ubiquitination and proteasomal degradation of RIP1 following
      disruption of Hsp90 binding.
AB  - Toll-like receptors (TLRs) play a crucial role in innate immunity by recognizing
      microbial pathogens. Triad3A is an E3 ubiquitin-protein ligase that interacts
      with the Toll/interleukin-1 receptor domain of TLRs and promotes their
      proteolytic degradation. In the present study, we further investigated its
      activity on signaling molecules downstream of TLRs and tumor necrosis factor
      (TNF) receptor 1. Triad3A promoted down-regulation of two TIR domain-containing
      adapter proteins, TIRAP and TRIF, as well as a RIP1 but had no effect on other
      adapter molecules in either the TLRs or TNF-alpha signaling pathways. Multiple
      sequence alignment analysis suggested that RIP1 contains a TIR homologous domain,
      and mutation of amino acid residues in this domain identified three residues
      critical for its interaction with Triad3A. Moreover, Triad3A acted as a negative
      regulator in TNF-alpha signaling. Reduction of Triad3A expression by small
      interference RNAs rendered cells hyperresponsive to TNF-alpha stimulation.
      Conversely, overexpression of Triad3A in cells blocked TNF-alpha-induced cell
      activation. This negative regulation was effected independently of changes in the
      cellular protein level of RIP1. Further studies indicated that RIP1 formed a
      complex with Triad3A and heat shock protein 90 (Hsp90), which is a chaperone
      protein capable of maintaining the stability of its client proteins. Treatment of
      cells with geldanamycin to disrupt the Hsp90 complex led to proteasomal
      degradation of RIP1. Depletion of Triad3A by small interference RNA treatment
      inhibited geldanamycin-activated ubiquitination and proteolytic degradation of
      RIP1. These results suggest that Triad3A is an E3 ubiquitin-protein ligase to
      RIP1 and that Hsp90 and Triad3A cooperatively maintain the homeostasis of RIP1.

PMID- 16968707
TI  - Beta-amyloid precursor protein is a direct cleavage target of HtrA2 serine
      protease. Implications for the physiological function of HtrA2 in the
      mitochondria.
AB  - The processing and metabolism of amyloid precursor protein (APP) is a major
      interest in Alzheimer disease (AD) research, because not only amyloid beta
      (Abeta) peptide, but also cellular or mitochondrial APP are intimately involved
      in cellular dysfunction and AD pathogenesis. Here we demonstrate that APP is
      directly and efficiently cleaved by the HtrA2 serine protease in vitro and in
      vivo. Using several APP mutants and N-terminal amino acid sequencing, we
      identified that the HtrA2-mediated APP cleavage product is the C161 fragment
      encompassing amino acids 535-695 of APP695. The immunofluorescence and
      subcellular fractionation studies indicate that APP is partly colocalized with
      HtrA2 in the mitochondria where HtrA2 can cleave APP under normal conditions. The
      HtrA2-cleaved C161 fragment was detected in the cytosolic fraction; therefore, we
      postulate that the C161 fragment is released into the cytosol after cleavage of
      APP by HtrA2. Interestingly, the level of C161 was remarkably decreased in motor
      neuron degeneration (mnd2) mice in which the serine protease activity of HtrA2
      was greatly reduced. These results show that the protease activity of HtrA2 is
      essential for the production of C161 and that processing of APP into C161 is a
      natural event occurring under normal physiological conditions. Our study suggests
      that the direct cleavage of mitochondrial APP by HtrA2 may prevent mitochondrial
      dysfunction caused by accumulation of APP and that the regulation of HtrA2
      protease activity may be a therapeutic target in AD.

PMID- 16968708
TI  - Functional compensation for adipose differentiation-related protein (ADFP) by
      Tip47 in an ADFP null embryonic cell line.
AB  - Ectopic accumulation of lipid droplets in non-adipose tissues correlates with the
      degree of insulin resistance in these tissues. Emerging evidence indicates that
      lipid droplets are specialized organelles that participate in lipid metabolism
      and intracellular trafficking. These properties are thought to derive from the
      lipid droplet-associated PAT protein family (perilipin, ADFP, and Tip47). The
      functions of the ubiquitously distributed adipose differentiation-related protein
      (ADFP) and Tip47 remain unknown. To evaluate the roles of ADFP and Tip47 in lipid
      biogenesis and metabolism, ADFP null and wild type (wt) clonal cell lines were
      established from ADFP null and wt mice, respectively. In ADFP null cells, Tip47
      was identified as the sole lipid droplet-associated protein from the PAT family
      by mass spectroscopy, which was further confirmed by immunoblotting and
      immunocytochemistry. Following incubation with oleic acid, ADFP null cells were
      able to form lipid droplets to the same extent as wt cells. No statistical
      differences between the two cell types were observed in NEFA uptake or lipolysis.
      Small interference RNAs (siRNAs) against Tip47 were found to down-regulate
      protein levels for Tip47 by 85%. ADFP null cells treated with Tip47 siRNA
      retained the ability to form lipid droplets but to a lesser extent and shunted
      the utilization of exogenously added NEFA from triglycerides to phospholipids.
      These data support the hypothesis that Tip47 plays an important role in lipid
      metabolism. Tip47 and ADFP in peripheral tissues may play a critical role in
      regulating the formation and turnover, and hence metabolic consequences, of
      ectopic fat.

PMID- 16968709
TI  - The orphan nuclear receptor Rev-erb alpha regulates circadian expression of
      plasminogen activator inhibitor type 1.
AB  - Plasminogen activator inhibitor type 1 (PAI-1) is a major physiologic regulator
      of the fibrinolytic system and has recently gained recognition as a modulator of
      inflammation and atherosclerosis. PAI-1 exhibits circadian rhythmicity in its
      expression, peaking in the early morning, which is associated with increased risk
      for cardiovascular events. However, the mechanisms that determine PAI-1 circadian
      rhythmicity remain poorly understood. We discovered that the orphan nuclear
      receptor Rev-erb alpha, a core component of the circadian loop, represses human
      PAI-1 gene expression through two Rev-erb alpha binding sites in the PAI-1
      promoter. Mutations of these sites, as well as RNA interference targeting
      endogenous Rev-erb alpha and its corepressors, led to increased expression of the
      PAI-1 gene. Furthermore, glycogen synthase kinase 3beta (GSK3beta) contributes to
      pai-1 repression by phosphorylating and stabilizing Rev-erb alpha protein, which
      can be blocked by lithium. Interestingly, serum shock generated circadian
      oscillations in PAI-1 mRNA in NIH3T3 cells, suggesting that PAI-1 is a direct
      output gene of the circadian loop. Ectopic expression of a stabilized form of Rev
      erb alpha that mimics GSK3beta phosphorylation dramatically dampened PAI-1
      circadian oscillations. Thus, our results suggest that Rev-erb alpha is a major
      determinant of the circadian PAI-1 expression and a potential modulator of the
      morning susceptibility to myocardial infarction.

PMID- 16968710
TI  - Characterization of a new thermophilic spore photoproduct lyase from Geobacillus
      stearothermophilus (SplG) with defined lesion containing DNA substrates.
AB  - The Geobacillus stearothermophilus splG gene encodes a thermophilic spore
      photoproduct lyase (SplG) that belongs to the family of radical S
      adenosylmethionine (AdoMet) enzymes. The aerobically purified apo-SplG forms a
      homodimer, which contains one [4Fe-4S] cluster per monomer unit after
      reconstitution to the holoform. Formation of the [4Fe-4S] cluster was proven by
      quantification of the amount of iron and sulfur per homodimer and by UV and EPR
      spectroscopy. The UV spectrum features a characteristic absorbance at 420 nm
      typical for [4Fe-4S] clusters, and the EPR data were found to be identical to
      those of other proteins containing an [4Fe-4S]+ center. Probing of the activity
      of the holo-SplG with oligonucleotides containing one spore photoproduct lesion
      at a defined site proved that the enzyme is able to turn over substrate. In
      addition to repair, we observed cleavage of AdoMet to generate 5'-deoxyadenosine.
      In the presence of aza-AdoMet the SplG is completely inhibited, which provides
      direct support for the repair mechanism.

PMID- 16968711
TI  - Indoor 222Rn concentration measurements in some buildings of Hebron province
      during the winter season of the year 2000.
AB  - In this study, we report on the indoor radon concentration levels in a number of
      locations scattered in the Hebron province, Palestine. The measurements were
      performed during the winter season of the year 1999/2000 using the CR-39
      detectors. The radon concentration levels were found to vary from 23 to 580 Bq m(
      3). The arithmetic average of the obtained radon concentration levels was found
      to be 91 Bq m(-3). It was found that most of the radon concentration levels in
      houses and school rooms are below the low reference levels limits. Most of the
      high-radon concentration levels were found in unpainted storage rooms.

PMID- 16968712
TI  - Development of LiF:Mg,Cu,Si TL material (new KLT-300) with a low-residual signal
      and high-thermal stability.
AB  - LiF-based thermoluminescence (TL) materials have been widely used for radiation
      dosimetry due to their attractive features. LiF:Mg,Cu,P is one of the most
      sensitive tissue-equivalent TL materials, approximately 40 times more sensitive
      than LiF:Mg,Ti (TLD-100), but it has two main drawbacks: a thermal loss of the TL
      sensitivity when annealed at temperatures>240 degrees C, and a relatively high
      residual signal. Recently, LiF:Mg,Cu,Na,Si TL material was developed to overcome
      these drawbacks at the Korea Atomic Energy Research Institute, but it provided
      only marginal improvements in reducing the residual signal. The newly developed
      LiF:Mg,Cu,Si TL material has a significantly lower residual signal and a better
      stability to thermal treatments. In this article, the preparation method and some
      dosimetric properties (sensitivity and residual signal) of the new LiF:Mg,Cu,Si
      TL material are presented. At the end of the preparation procedures, a dual-step
      annealing method is introduced and this has proved as a very efficient method to
      reduce the high-temperature peak and is the cause of residual signal. Therefore,
      the high-temperature peak in the glow curve was significantly reduced. The
      sensitivity is approximately 20 times higher than that of TLD-100 and the
      residual signal was estimated to be approximately 0.04%.

PMID- 16968713
TI  - Radiophotoluminescence dosimetry using a small spherical glass: a preliminary
      phantom study.
AB  - A radiophotoluminescence dosimetry has been proposed using a spherical silver
      activated phosphate glass with a diameter of 1.5 mm. A 6 MV photon dose of 2 Sv
      (2 Gy) was delivered to 14 spherical glass samples placed between two solid water
      phantoms at a depth of 10 cm. The samples were positioned within a 20 x 20 mm(2)
      centred at beam axis to ensure uniform dose absorption. A normalised output from
      a read-out system was obtained by simultaneously measuring luminescence from a
      non-irradiated reference and that from an irradiated reference to eliminate
      background contamination and time-varying fluctuation of the readout system,
      leading to a normalised standard deviation of 1.8%. A dose up to 3.5 Sv (3.5 Gy)
      was delivered to three spherical glass samples positioned between two solid water
      phantoms at a depth of 10 cm. The normalised output increased linearly with the
      applied dose.

PMID- 16968714
TI  - Maps and meanings.

PMID- 16968716
TI  - Severe intravascular haemolysis and acute renal failure following intravenous
      administration of iron dextran.

PMID- 16968715
TI  - Etanercept 50 mg once weekly is as effective as 25 mg twice weekly in patients
      with ankylosing spondylitis.
AB  - OBJECTIVE: To compare the efficacy, pharmacokinetics and safety of etanercept 50
      mg once weekly with 25 mg twice weekly and placebo in patients with ankylosing
      spondylitis. METHODS: A 12-week, double-blind, placebo-controlled study compared
      the effects of etanercept 50 mg once weekly, etanercept 25 mg twice weekly and
      placebo in 356 patients with active ankylosing spondylitis (3:3:1 randomisation,
      respectively). The primary end point was the proportion of patients achieving a
      response at week 12 based on the Assessment in Ankylosing Spondylitis Working
      Group criteria (ASAS 20). The pharmacokinetics of etanercept 50 mg once weekly
      and 25 mg twice weekly were analysed. RESULTS: Baseline characteristics and
      disease activity were similar among the three groups: etanercept 50 mg once
      weekly, etanercept 25 mg twice weekly and placebo. The percentage of patients
      discontinuing therapy was 9.0%, 9.3% and 13.7% for the three respective groups.
      ASAS 20 response at 12 weeks was achieved by 74.2% of patients with etanercept 50
      mg once weekly and 71.3% of those with etanercept 25 mg twice weekly, both
      significantly higher than the percentage of patients taking placebo (37.3%,
      p<0.001). Percentages of patients with ASAS 5/6 response (70.3%, 72.0% and 27.5%,
      respectively; p<0.001) and those with ASAS 40 response (58.1%, 53.3% and 21.6%,
      respectively; p<0.001) followed a similar pattern. Significant improvement
      (p<0.05) was seen in measures of disease activity, back pain, morning stiffness
      and C reactive protein levels as early as 2 weeks. Serum etanercept exposure was
      similar between the etanercept groups. Incidence of treatment-emergent adverse
      events, including infections, was similar among all three groups, and no
      unexpected safety issues were identified. CONCLUSIONS: Patients with ankylosing
      spondylitis can expect a comparable significant improvement in clinical outcomes
      with similar safety when treated with etanercept 50 mg once weekly or with 25 mg
      twice weekly.

PMID- 16968717
TI  - Gemcitabine-induced thrombotic microangiopathy: a systematic review.

PMID- 16968718
TI  - Do statins protect the kidney as well as the heart?

PMID- 16968720
TI  - Complement-ary matching: A definite maybe.

PMID- 16968719
TI  - Induction and long-term treatment with cyclosporine in membranous nephropathy
      with the nephrotic syndrome.
AB  - BACKGROUND: Cyclosporine A (CyA) has been shown to be effective in membranous
      nephropathy (MN). However, the optimal dose and the duration of treatment remain
      controversial issues. We evaluated the efficacy of low-dose CyA alone or combined
      with corticosteroids as induction and long-term treatment for nephrotic patients
      with MN. METHODS: In the first part of the study, 51 nephrotic patients with MN
      were treated either with CyA and prednisolone (n=31) or CyA alone (n=20) for 12
      months. Patients who responded with complete remission (CR) or partial remission
      (PR) were placed on long-term treatment with lower doses of CyA and prednisolone
      or CyA alone. The mean follow-up of the second part of the study was 26+/-16
      months and 18+/-7 months, respectively. RESULTS: After 12 months of treatment, 26
      patients in the combination group and 17 patients in the monotherapy group had a
      CR or PR of proteinuria (P=NS). Renal function was unchanged in the two groups.
      During long-term treatment relapses were more frequent in the monotherapy group
      (47 vs 15%, P<0.05). Daily CyA dose was higher in non-relapsers in both groups
      (combination 1.4+/-0.5 vs 1.0+/-0.3 mg/kg, P<0.001, monotherapy 1.5+/-0.4 vs
      1.1+/-0.2 mg/kg, P<0.003). Relapsers in both groups had lower CyA trough levels
      (72+/-48 ng/ml) compared with non-relapsers (194+/-80 ng/ml) (P<0.03). Renal
      function and proteinuria remained stable during the follow-up. CONCLUSION: This
      study suggests that 12-month therapy with CyA (+/-prednisolone) is effective in
      inducing remission in most nephrotic patients with MN and well-preserved renal
      function. Longer treatment with lower doses is a useful approach to maintain
      remission. Relapses occur more frequently in the monotherapy group and usually
      are associated with CyA trough levels<100 ng/ml.

PMID- 16968721
TI  - Angiotensin converting enzyme inhibition prevents development of collapsing focal
      segmental glomerulosclerosis in Thy-1.1 transgenic mice.
AB  - BACKGROUND: Thy-1.1 transgenic mice develop hypercellular focal and segmental
      glomerulosclerosis (FSGS) lesions that mimic human collapsing FSGS, in 7 days
      after injection with anti-Thy-1.1 antibodies. These lesions consist of
      proliferating parietal epithelial cells (PECs). We questioned whether the
      angiotensin converting enzyme inhibitor (ACE), captopril, could prevent the
      development of FSGS and if protection is related to the timing of drug
      administration. METHODS: First, we compared the effect of captopril treatment
      with angiotensin II-(ANGII) independent antihypertensive therapy (triple
      therapy). Second, we tested the effects of captopril administered over four
      different time intervals: days -7 to 0 (Ca-7>0), days -7 to 7 (Ca-7>7), days 0-7
      (Ca0>7) and days 3-7 (Ca3>7) (day 0 being the day of injection of the antibody).
      RESULTS: In anti-Thy-1.1 injected control (C) mice we observed dedifferentiation
      and activation of podocytes, reflected by loss of ASD33 and increased expression
      of desmin, followed by a marked accumulation of PECs forming hypercellular
      lesions. PECs showed an increased expression of connective tissue growth factor
      (CTGF). Triple therapy or captorpil pre-treatment (Ca-7>0) had no significant
      effect on albuminuria or FSGS. In contrast, Ca0>7 and Ca3>7 treatment
      significantly lowered albuminuria and attenuated development of FSGS. The latter
      two treatments attenuated loss of ASD33 expression by podocytes but could not
      prevent increased desmin expression. In addition, these treatments reduced CTGF
      expression by PECs and prevented PEC proliferation. CONCLUSIONS: ACE inhibition,
      but not triple therapy, prevents the development of FSGS, suggesting an important
      role for ANGII. ACE inhibition has a protective effect even when started 3 days
      after the initial podocyte insult, which is probably related to the ability of
      ACE-inhibition to block PEC activation and proliferation.

PMID- 16968722
TI  - Effect of peritoneal dialysis on renal morphology and function.
AB  - BACKGROUND: Results of clinical studies suggest that peritoneal dialysis (PD) is
      less harmful to the residual renal function than haemodialysis. However, we have
      no objective data describing the potential injuring effect of PD to kidney. We
      studied in rats after unilateral nephrectomy changes in renal structure and
      function after 12 weeks exposure to standard, glucose-based PD fluid. METHODS:
      One month after removing one kidney PD catheters were implanted in rats and
      during the following 12 weeks, twice a day, animals were infused with 20 ml of
      3.9% glucose dialysis fluid containing high concentration of glucose degradation
      products. Rats not infused with the dialysis fluid served as control (CON). At
      the beginning and after 12 weeks of the study renal creatinine clearance, urinary
      excretion of albumin, N-acetyl-beta-glucosaminidase (NAG) and cytokines were
      measured. Concentration of malondialdehyde (MDA), advanced glycation end products
      (AGEs) and monocyte chemoattractant protein-1 (MCP-1) were measured in serum
      samples. Morphology of the kidneys was evaluated in the light microscope.
      RESULTS: After 12 weeks exposure to the dialysis fluid serum MDA, AGEs and MCP
      levels were increased as compared with CON by 80%, P < 0.002, 29%, P < 0.05 and
      71%, P < 0.005, respectively. Renal clearance of creatinine was comparable in
      both groups, but urinary excretion of albumin was increased by 55% in control
      group and by 160% in the studied group, P < 0.001; whereas urinary excretion of
      NAG was not changed in control group but increased by 125% in the studied group,
      P < 0.01. Increase of the remnant kidney's weight was higher (+77%, P < 0.01) in
      the CON group, but accumulation of the extramesangial matrix in glomeruli and
      collagen in the peritubular space was stronger in the studied group by 69%, P <
      0.0001 and 274%, P < 0.0001, respectively. CONCLUSION: Chronic exposure of rats
      to the glucose-based dialysis fluid causes morphological changes in the renal
      glomeruli similar to diabetic nephropathy. Albuminuria increases what may
      accelerate progression of the kidney damage.

PMID- 16968723
TI  - Mycotic pseudoaneurysms in a CAPD patient.

PMID- 16968724
TI  - Risk factors for Mycobacterium tuberculosis in US chronic dialysis patients.
AB  - BACKGROUND: End-stage renal disease is known to disrupt the cell-mediated immune
      response that is responsible for the killing of intracellular organisms such as
      Mycobacterium tuberculosis. Risk factors that contribute to the development of
      tuberculosis (TB) disease in the US dialysis population have not been studied on
      a large scale. METHODS: A retrospective cohort study of TB disease in 272,024
      patients in the US Renal Data System initiated on dialysis therapy between 1
      April 1995 and 31 December 1999 with Medicare or Medicaid as primary payer were
      analysed. A total of 21 risk factors were analysed. RESULTS: Among the US
      population studied, there is a 1.2 and 1.6% cumulative incidence of TB in
      patients undergoing either peritoneal or haemodialysis, respectively. Ten risk
      factors for TB that proved to be statistically significant included advanced age
      (P<0.001), unemployment (P<0.001), Medicaid insurance (P<0.001), reduced body
      mass index (P<0.001), decreased serum albumin (P<0.001), haemodialysis (P=0.019),
      both Asian (P=0.010) and Native American (P=0.020) race, ischaemic heart disease
      (P=0.032), smoking (P=0.010), illicit drug use (P=0.018) and anaemia (P=0.028).
      TB was independently associated with increased mortality, adjusted hazard ratio
      (AHR) 1.42 (95% CI 1.18-1.70, P<0.001). CONCLUSIONS: The prevalence of TB disease
      in the US dialysis population is low compared with worldwide rates; however, the
      disease is associated with increased mortality. Of the 10 significant risk
      factors identified, five are potentially modifiable.

PMID- 16968725
TI  - Pruritus in haemodialysis patients: International results from the Dialysis
      Outcomes and Practice Patterns Study (DOPPS).
AB  - BACKGROUND: Pruritus affects many haemodialysis (HD) patients. In this study,
      pruritus and its relationship to morbidity, mortality, quality of life (QoL),
      sleep quality and patient laboratory measures were analysed in >300 dialysis
      units in 12 countries. METHODS: Pruritus data were collected from 18 801 HD
      patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS) (1996
      2004). Analyses were adjusted for age, gender, black race, Kt/V, haemoglobin,
      serum albumin, albumin-corrected serum calcium, serum phosphorus, 13
      comorbidities, depression, years on dialysis, country and facility clustering
      effects. RESULTS: Moderate to extreme pruritus was experienced by 42% of
      prevalent HD patients in DOPPS during 2002/2003. Many patient characteristics
      were significantly associated with pruritus, but this did not explain the large
      differences in pruritus between countries (ranging from 36% in France to 50% in
      the UK) and between facilities (5-75%). Pruritus was slightly less common in
      patients starting HD than in patients on dialysis >3 months. Pruritus in new end
      stage renal disease (ESRD) patients likely results from pre-existing conditions
      and not haemodialysis per se, indicating the need to understand development of
      pruritus before ESRD. Patients with moderate to extreme pruritus were more likely
      to feel drained [adjusted odds ratio (AOR) = 2.3-5.2, P < 0.0001] and to have
      poor sleep quality (AOR = 1.9-4.1, P < or = 0.0002), physician-diagnosed
      depression (AOR = 1.3-1.7, P < or = 0.004), and QoL mental and physical composite
      scores 3.1-8.6 points lower (P < 0.0001) than patients with no/mild pruritus.
      Pruritus in HD patients was associated with a 17% higher mortality risk (P <
      0.0001), which was no longer significant after adjusting for sleep quality
      measures. CONCLUSIONS: The pruritus/mortality relationship may be substantially
      attributed to poor sleep quality. The many poor outcomes associated with pruritus
      underscore the need for better therapeutic agents to provide relief for the 40
      50% of HD patients affected by pruritus.

PMID- 16968726
TI  - Is early treatment of anaemia with epoetin-alpha beneficial to pre-dialysis
      chronic kidney disease patients? Results of a multicentre, open-label,
      prospective, randomized, comparative group trial.
AB  - BACKGROUND: This multicentre, open-label prospective, randomized, comparative
      group study evaluated the effects of maintaining haemoglobin (Hb) in pre-dialysis
      chronic kidney disease (CKD) patients. METHODS: A total of 197 patients were
      randomized to start subcutaneous epoetin-alpha (SC-EPO; EPREX; 1000 U twice
      weekly) at an early stage of anaemia to maintain Hb at 11.0 +/- 1.0 g/dl (group
      A, n = 65), or to allow Hb to fall to < or =9.0 g/dl before starting SC-EPO
      (group B, n = 132) (2000 U three times weekly); and subsequently maintaining Hb
      at 11.0 +/- 1.0 g/dl. RESULTS: Of 132 patients randomized to group B, 55
      progressed to treatment (-trigger). The study was prematurely terminated due to
      contraindication of the subcutaneous administration route. Mean weekly EPO doses
      at 1 year were 1471 U for group A; 820 U for group B; final doses were 2281 U for
      group A; 2099 U for group B. There was no significant difference between groups A
      and B with regard to left ventricular mass (-12.5 vs -9.7%; P = 0.82). In groups
      A and B, 48% and 52%, respectively, terminated the study because of
      dialysis/death, after a median of 36.3 and 27.3 months, respectively. CONCLUSION:
      Early intervention to correct anaemia in CKD patients did not have a significant
      impact on LVM, the primary efficacy variable. Time to dialysis/death was not
      significantly different between groups A and B.

PMID- 16968727
TI  - Perplexing hyperkalaemia.

PMID- 16968728
TI  - Levofloxacin and rhabdomyolysis in a renal transplant patient.

PMID- 16968729
TI  - Does angiotensin blockade influence graft outcome in renal transplant recipients
      with IgA nephropathy?
AB  - BACKGROUND: IgA nephropathy (IgAN) is a frequent cause of end-stage renal disease
      (ESRD) and recurrent disease causes deterioration and graft loss in transplant
      recipients. No definitive management is known to reduce the risk or severity of
      recurrent IgAN, and the evidence to support the use of renin-angiotensin system
      blockade in such patients is limited. METHODS: All 1137 renal transplants
      performed at the Belfast City Hospital over a 27-year period were reviewed. A
      total of 75 patients with ESRD due to biopsy-proven IgAN were identified; 39 of
      them had been prescribed an angiotensin-converting enzyme inhibitor (ACEi) or
      angiotensin-II type I receptor blocker (ARB). RESULTS: The two groups were well
      matched in terms of demographic details, immunosuppressive regimens and duration
      of follow-up (median 65 months, range 18-261 months). The 5- and 10-year graft
      survivals were higher in those prescribed ACEi/ARB therapy compared with those
      who were not, although these differences did not reach statistical significance
      (92.9 vs 86.5%; P = 0.34 and 81.6 vs 72.7%; P = 0.32, respectively). These
      results were similar when censored for death with a functioning graft. In the
      group where an ACEi/ARB was not prescribed, all four with biopsy-proven recurrent
      IgAN progressed to ESRD, compared with three out of nine in the group treated
      with an ACEi/ARB. CONCLUSIONS: In transplant recipients with ESRD due to biopsy
      proven IgAN, a trend towards improved 5-year and 10-year graft survival was seen
      in those prescribed ACEi/ARBs. All with recurrent IgAN in their grafts who were
      not treated with ACEi/ARB therapy progressed again to ESRD.

PMID- 16968730
TI  - Mast cells and the power of local RAS activation.

PMID- 16968731
TI  - A case of successful double sequential bone marrow and kidney transplantations in
      a patient with multiple myeloma.

PMID- 16968732
TI  - Thrombophilia and avascular necrosis of femoral head in kidney allograft
      recipients.
AB  - BACKGROUND: Thrombophilia has been implicated in the development of avascular
      necrosis (AVN) in various diseases. We aimed to search for the relation of both
      prothrombin gene G20210A mutation and factor V G1691A (factor V Leiden) mutation
      with AVN among kidney transplant recipients. METHODS: Nineteen patients with AVN
      and 38 control patients without AVN were included. Clinical information was
      collected, and gender, age, type of renal allograft, duration and type of
      dialysis, presence of acute rejection, and cumulative doses of ciclosporin and
      corticosteroid administration were taken into consideration. Genotypes of factor
      V G1691A and prothrombin G20210A were determined by direct sequencing of genomic
      DNA. RESULTS: Factor V Leiden mutation was detected in six patients (31.6%) among
      patients with AVN and in only three patients (7.9%) in the control group (P =
      0.048). Two patients (10.5%) in the AVN group were determined to have prothrombin
      G20210A mutation, while no prothrombin G20210A mutation was detected in the
      control group. When both of the mutations causing thrombophilia were considered,
      a total of eight patients (42.1%) in the AVN group and three patients (7.9%) in
      the control group were identified (P = 0.004). CONCLUSION: Thrombophilia seems to
      be an important risk factor for development of AVN. More studies are needed to
      clarify the role of factor V G1691A and prothrombin G20210A mutation for AVN.

PMID- 16968733
TI  - Paulista Registry of glomerulonephritis: 5-year data report.
AB  - BACKGROUND: The Paulista Registry of Glomerulopathies was created in May 1999 and
      comprises several centres of Sao Paulo, the most populous Brazilian State, that
      concentrates people from all regions of the country who look for health care.
      METHODS: This report includes data from 2086 patients from Brazil submitted to
      renal biopsy due to the presumed diagnosis of glomerular diseases, registered
      prospectively since May 1999 until January 2005. Data were collected by the
      integrants of the 11 centres involved, utilizing a standardized questionnaire.
      RESULTS: The mean age of the patients was 34.5+/-14.6 years. Primary glomerular
      diseases were more frequent in males (55.1%) than in females; on the other hand,
      secondary glomerular diseases were more frequent in females (71.8%). The most
      common clinical presentation was nephrotic syndrome and the frequency of
      hypertension, at this time, was 55.5%. There was a predominance of indication of
      biopsies in the third, fourth and fifth decades of life. The most common primary
      glomerular diseases were focal and segmental glomerulosclerosis (29.7%), followed
      by membranous nephropathy (20.7%), IgA nephropathy (17.8%), minimal change
      disease (9.1%), membranoproliferative glomerulonephritis (7%), crescentic
      glomerulonephritis (4.1%), advanced chronic glomerulopathy (4%), non-IgA
      mesangial glomerulonephritis (3.8%), diffuse proliferative glomerulonephritis
      (2.5%), focal segmental proliferative glomerulonephritis (1%) and others (0.3%).
      The most frequent secondary glomerular disease was lupus nephritis, corresponding
      to 66.2% of the cases, followed by post-infectious glomerulonephritis (12.5%),
      diabetic nephropathy (6.2%), diseases associated to paraproteinaemia (4.9%),
      hereditary diseases (4.6%), vasculitis (3.2%), malignancies (0.9.%), secondary
      focal segmental glomerulosclerosis (0.6%) and others (0.9%). CONCLUSION: Focal
      segmental glomerulosclerosis was the most frequent primary glomerular disease,
      followed by membranous nephropathy and IgA nephropathy. Lupus nephritis
      predominated over all the other secondary glomerular diseases.

PMID- 16968734
TI  - Genetics and clinical features of 15 Asian families with steroid-resistant
      nephrotic syndrome.

PMID- 16968735
TI  - Cytotoxicity of a mutant huntingtin fragment in yeast involves early alterations
      in mitochondrial OXPHOS complexes II and III.
AB  - Mitochondrial dysfunction may play an important role in the pathogenic mechanism
      of Huntington's disease (HD). However, the exact mechanism by which mutated
      huntingtin could cause bioenergetic dysfunction is still unknown. We have
      constructed a stable inducible yeast model of HD by expressing a human huntingtin
      fragment containing a mutant polyglutamine tract of 103Q fused to green
      fluorescent protein (GFP), and a control expressing a wild-type 25Q domain fused
      to GFP in a wild-type strain. We showed that in yeast cells expressing 103Q, cell
      respiration was progressively reduced after 4-6 h of induction with galactose,
      down to 50% of the control after 10 h of induction. The cell respiration defect
      results from an alteration in the function and amount of mitochondrial
      respiratory chain complex II+III, in congruency to data obtained from postmortem
      brain of HD patients and from toxin models. In our model, the production of
      reactive oxygen species (ROS) is significantly enhanced in cells expressing 103Q.
      Quenching of ROS with resveratrol partially prevents the cell respiration defect.
      Mitochondrial morphology and distribution were also altered in cells expressing
      103Q, probably resulting from the interaction of aggregates with portions of the
      mitochondrial web and from a progressive disruption of the actin cytoskeleton. We
      propose a mechanism for mitochondrial dysfunction in our yeast model of HD in
      which the interactions of misfolded/aggregated polyglutamine domains with the
      mitochondrial and actin networks lead to disturbances in mitochondrial
      distribution and function and to increase in ROS production. Oxidative damage
      could preferentially affect the stability and function of enzymes containing iron
      sulfur clusters such as complexes II and III. Our yeast model represents a very
      useful paradigm to study mitochondrial physiology alterations in the pathogenic
      mechanism of HD.

PMID- 16968736
TI  - Bathing suit ichthyosis is caused by transglutaminase-1 deficiency: evidence for
      a temperature-sensitive phenotype.
AB  - Bathing suit ichthyosis (BSI) is a striking and unique clinical form of autosomal
      recessive congenital ichthyosis characterized by pronounced scaling on the
      bathing suit areas but sparing of the extremities and the central face. Here we
      report on a series of 10 BSI patients. Our genetic, ultrastructural and
      biochemical investigations show that BSI is caused by transglutaminase-1 (TGase
      1) deficiency. Altogether, we identified 13 mutations in TGM1-among them seven
      novel missense mutations and one novel nonsense mutation. Structural modeling for
      the Tyr276Asn mutation reveals that the residue is buried in the hydrophobic
      interior of the enzyme and that the hydroxyl side chain of Tyr276 is exposed to
      solvent in a cavity of the enzyme. Cryosections of healthy skin areas
      demonstrated an almost normal TGase activity, in contrast to the affected BSI
      skin, which only showed a cytoplasmic and clearly reduced TGase-1 activity. The
      distribution of TGase-1 substrates in the epidermis of affected skin corresponded
      to the situation in TGase-1 deficiency. Interestingly, the expression of TGase-3
      and cathepsin D was reduced. Digital thermography validated a striking
      correlation between warmer body areas and presence of scaling in patients
      suggesting a decisive influence of the skin temperature. In situ TGase testing in
      skin of BSI patients demonstrated a marked decrease of enzyme activity when the
      temperature was increased from 25 to 37 degrees C. We conclude that BSI is caused
      by TGase-1 deficiency and suggest that it is a temperature-sensitive phenotype.

PMID- 16968737
TI  - Trimerisation is important for the function of clathrin at the mitotic spindle.
AB  - Clathrin is a triskelion consisting of three heavy chains each with an associated
      light chain. During mitosis, clathrin contributes to kinetochore fibre stability.
      As the N-terminal domain at the foot of each leg can bind to the mitotic spindle,
      we proposed previously a ;bridge hypothesis' wherein clathrin acts as a brace
      between two or three microtubules within a kinetochore fibre to increase fibre
      stability. Here, we have tested this hypothesis by replacing endogenous clathrin
      heavy chain in human cells with a panel of clathrin constructs. Mutants designed
      to abolish trimerisation were unable to rescue the mitotic defects caused by
      depletion of endogenous clathrin. By contrast, stunted triskelia with contracted
      legs could partially rescue normal mitosis. These results indicate that the key
      structural features of clathrin that are necessary for its function in mitosis
      are a trimeric molecule with a spindle interaction domain at each end, supporting
      the bridge hypothesis for clathrin function in mitosis.

PMID- 16968738
TI  - Selective membrane exclusion in phagocytic and macropinocytic cups.
AB  - Specialized eukaryotic cells can ingest large particles and sequester them within
      membrane-delimited phagosomes. Many studies have described the delivery of
      lysosomal proteins to the phagosome, but little is known about membrane sorting
      during the early stages of phagosome formation. Here we used Dictyostelium
      discoideum amoebae to analyze the membrane composition of newly formed
      phagosomes. The membrane delimiting the closing phagocytic cup was essentially
      derived from the plasma membrane, but a subgroup of proteins was specifically
      excluded. Interestingly the same phenomenon was observed during the formation of
      macropinosomes, suggesting that the same sorting mechanisms are at play during
      phagocytosis and macropinocytosis. Analysis of mutant strains revealed that
      clathrin-associated adaptor complexes AP-1, -2 and -3 were not necessary for this
      selective exclusion and, accordingly, ultrastructural analysis revealed no
      evidence for vesicular transport around phagocytic cups. Our results suggest the
      existence of a new, as yet uncharacterized, sorting mechanism in phagocytic and
      macropinocytic cups.

PMID- 16968739
TI  - IFTA-2 is a conserved cilia protein involved in pathways regulating longevity and
      dauer formation in Caenorhabditis elegans.
AB  - Defects in cilia are associated with diseases and developmental abnormalities.
      Proper cilia function is required for sonic hedgehog and PDGFRalpha signaling in
      mammals and for insulin-like growth factor (IGF) signaling in Caenorhabditis
      elegans. However, the role of cilia in these pathways remains unknown. To begin
      addressing this issue, we are characterizing putative cilia proteins in C.
      elegans that are predicted to have regulatory rather than structural functions.
      In this report, we characterized the novel cilia protein T28F3.6 (IFTA-2,
      intraflagellar transport associated protein 2), which is homologous to the
      mammalian Rab-like 5 protein. We found that, unlike the intraflagellar transport
      (IFT) genes, disruption of ifta-2 does not result in overt cilia assembly
      abnormalities, nor did it cause chemotaxis or osmotic avoidance defects typical
      of cilia mutants. Rather, ifta-2 null mutants have an extended lifespan phenotype
      and are defective in dauer formation. Our analysis indicates that these
      phenotypes result from defects in the DAF-2 (insulin-IGF-1-like) receptor
      signaling pathway in ciliated sensory neurons. We conclude that IFTA-2 is not a
      ciliogenic protein but rather is a regulator of specific cilia signaling
      activities. Interestingly, a mammalian IFTA-2 homolog is also found in cilia,
      raising the possibility that its function has been conserved during evolution.

PMID- 16968740
TI  - Characterization of a novel meiosis-specific protein within the central element
      of the synaptonemal complex.
AB  - During the first meiotic prophase, alignment and synapsis of the homologous
      chromosomes are mediated by the synaptonemal complex. Incorrect assembly of this
      complex results in cell death, impaired meiotic recombination and formation of
      aneuploid germ cells. We have identified a novel mouse meiosis-specific protein,
      TEX12, and shown it to be a component of the central element structure of the
      synaptonemal complex at synapsed homologous chromosomes. Only two other central
      element proteins, SYCE1 and SYCE2, have been identified to date and, using
      several mouse knockout models, we show that these proteins and TEX12 specifically
      depend on the synaptonemal transverse filament protein SYCP1 for localization to
      the meiotic chromosomes. Additionally, we show that TEX12 exactly co-localized
      with SYCE2, having the same, often punctate, localization pattern. SYCE1, on the
      other hand, co-localized with SYCP1 and these proteins displayed the same more
      continuous expression pattern. These co-localization studies were confirmed by co
      immunoprecipitation experiments that showed that TEX12 specifically co
      precipitated with SYCE2. Our results suggest a molecular network within the
      central elements, in which TEX12 and SYCE2 form a complex that interacts with
      SYCE1. SYCE1 interacts more directly with SYCP1 and could thus anchor the central
      element proteins to the transverse filaments.

PMID- 16968741
TI  - A novel endothelial-specific heat shock protein HspA12B is required in both
      zebrafish development and endothelial functions in vitro.
AB  - A zebrafish transcript dubbed GA2692 was initially identified via a whole-mount
      in situ hybridization screen for vessel specific transcripts. Its mRNA expression
      during embryonic development was detected in ventral hematopoietic and
      vasculogenic mesoderm and later throughout the vasculature up to 48 hours post
      fertilization. Morpholino-mediated knockdown of GA2692 in embryos resulted in
      multiple defects in vasculature, particularly, at sites undergoing active
      capillary sprouting: the intersegmental vessels, sub-intestinal vessels and the
      capillary sprouts of the pectoral fin vessel. During the course of these studies,
      a homology search indicated that GA2692 is the zebrafish orthologue of mammalian
      HspA12B, a distant member of the heat shock protein 70 (Hsp70) family. By a
      combination of northern blot and real-time PCR analysis, we showed that HspA12B
      is highly expressed in human endothelial cells in vitro. Knockdown of HspA12B by
      small interfering RNAs (siRNAs) in human umbilical vein endothelial cells blocked
      wound healing, migration and tube formation, whereas overexpression of HspA12B
      enhanced migration and accelerated wound healing - data that are consistent with
      the in vivo fish phenotype obtained in the morpholino-knockdown studies.
      Phosphorylation of Akt was consistently reduced by siRNAs against HspA12B.
      Overexpression of a constitutively active form of Akt rescued the inhibitory
      effects of knockdown of HspA12B on migration of human umbilical vein endothelial
      cells. Collectively, our data suggests that HspA12B is a highly endothelial-cell
      specific distant member of the Hsp70 family and plays a significant role in
      endothelial cells during development and angiogenesis in vitro, partially
      attributable to modulation of Akt phosphorylation.

PMID- 16968742
TI  - Silencing profilin-1 inhibits endothelial cell proliferation, migration and cord
      morphogenesis.
AB  - Expression of several actin-binding proteins including profilin-1 is up-regulated
      during capillary morphogenesis of endothelial cells, the biological significance
      of which remains unknown. Specifically, we hypothesized that profilin-1 is
      important for endothelial migration and proliferation. In this study, we
      suppressed profilin-1 expression in human umbilical vein endothelial cells by RNA
      interference. Gene silencing of profilin-1 led to significant reduction in the
      formation of actin filaments and focal adhesions. Loss of profilin-1 expression
      was also associated with reduced dynamics of cell-cell adhesion. Data from both
      wound-healing experiments and time-lapse imaging of individual cells showed
      inhibition of cell migration when profilin-1 expression was suppressed. Cells
      lacking profilin-1 exhibited defects in membrane protrusion, both in terms of its
      magnitude and directional persistence. Furthermore, loss of profilin-1 expression
      inhibited cell growth without compromising cell survival, at least in the short
      term, thus suggesting that profilin-1 also plays an important role in endothelial
      proliferation as hypothesized. Finally, silencing profilin-1 expression
      suppressed matrigel-induced early cord morphogenesis of endothelial cells. Taken
      together, our data suggest that profilin-1 may play important role in biological
      events that involve endothelial proliferation, migration and morphogenesis.

PMID- 16968743
TI  - Regulation of epidermal homeostasis and repair by phosphoinositide 3-kinase.
AB  - The epidermis undergoes continuous self-renewal to maintain its protective
      function. Whereas growth factors are known to modulate overall skin homeostasis,
      the intracellular signaling pathways, which control the delicate balance between
      proliferation and differentiation in keratinocytes, are largely unknown. Here we
      show transient upregulation of the phosphoinositide 3-kinase (PI3K) catalytic
      subunits p110alpha and p110beta in differentiating keratinocytes in vitro,
      expression of these subunits in the epidermis of normal and wounded skin, and
      enhanced Akt phosphorylation in the hyperproliferative wound epidermis.
      Stimulation of PI3K activity in cultured keratinocytes by stable expression of an
      inducible, constitutively active PI3K mutant promoted cell proliferation and
      inhibited terminal differentiation in keratinocyte monocultures and induced the
      formation of a hyperplastic, disorganized and poorly differentiated epithelium in
      organotypic skin cultures. Activation of PI3K signaling also caused
      reorganization of the actin cytoskeleton and induced keratinocyte migration in
      vitro and in skin organ cultures. The identification of 122 genes, which are
      differentially expressed after induction of PI3K signaling provides insight into
      the molecular mechanisms underlying the observed effects of active PI3K on
      keratinocytes and indicates that hyperproliferation may be achieved at the
      expense of genome integrity. These results identify PI3K as an important
      intracellular regulator of epidermal homeostasis and repair.

PMID- 16968744
TI  - Nucleo-cytoplasmic shuttling of human Kank protein accompanies intracellular
      translocation of beta-catenin.
AB  - The human Kank protein has a role in controlling the formation of the
      cytoskeleton by regulating actin polymerization. Besides the cytoplasmic
      localization as reported before, we observed the nuclear localization of Kank in
      OS-RC-2 cells. To uncover the mechanism behind this phenomenon, we focused on the
      nuclear localization signal (NLS) and the nuclear export signal (NES). We found
      one NLS (NLS1) and two NESs (NES1 and NES2) in the N-terminal region of Kank-L
      that were absent in Kank-S, and another NLS (NLS2) and NES (NES3) in the common
      region. These signals were active as mutations introduced into them abolished the
      nuclear import (for NLS1 and NLS2) or the nuclear export (for NES1 to NES3) of
      Kank. The localization of Kank in the cells before and after treatment with
      leptomycin B suggested that the transportation of Kank from the nucleus to the
      cytoplasm was mediated by a CRM1-dependent mechanism. TOPFLASH reporter assays
      revealed a positive relationship between the nuclear import of Kank and the
      activation of beta-catenin-dependent transcription. Kank can bind to beta-catenin
      and regulate the subcellular distribution of beta-catenin. Based on the findings
      shown here, we propose that Kank has multiple functions in the cells and plays
      different roles in the cytoplasm and the nucleus.

PMID- 16968745
TI  - Visualisation of macropinosome maturation by the recruitment of sorting nexins.
AB  - We report that phosphoinositol-binding sorting nexin 5 (SNX5) associates with
      newly formed macropinosomes induced by EGF stimulation. We used the recruitment
      of GFP-SNX5 to macropinosomes to track their maturation. Initially, GFP-SNX5 is
      sequestered to discrete subdomains of the macropinosome; these subdomains are
      subsequently incorporated into highly dynamic, often branched, tubular
      structures. Time-lapse videomicroscopy revealed the highly dynamic extension of
      SNX5-labelled tubules and their departure from the macropinosome body to follow
      predefined paths towards the perinuclear region of the cell, before fusing with
      early endosomal acceptor membranes. The extension and departure of these tubular
      structures occurs rapidly over 5-10 minutes and is dependent upon intact
      microtubules. As the tubular structures depart from the macropinosome there is a
      reduction in the surface area and an increase in tension of the limiting membrane
      of the macropinosome. In addition to the recruitment of SNX5 to the
      macropinosome, Rab5, SNX1 and EEA1 are also recruited by newly formed
      macropinosomes, followed by the accumulation of Rab7. SNX5 forms heterodimers
      with SNX1 and this interaction is required for endosome association of SNX5. We
      propose that the departure of SNX5-positive tubules represents a rapid mechanism
      of recycling components from macropinosomes thereby promoting their maturation
      into Rab7-positive structures. Collectively these findings provide a detailed
      real-time characterisation of the maturation process of the macropinocytic
      endosome.

PMID- 16968746
TI  - Dynamin-related proteins Vps1p and Dnm1p control peroxisome abundance in
      Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae contains three dynamin-related-proteins, Vps1p, Dnm1p
      and Mgm1p. Previous data from glucose-grown VPS1 and DNM1 null mutants suggested
      that Vps1p, but not Dnm1p, plays a role in regulating peroxisome abundance. Here
      we show that deletion of DNM1 also results in reduction of peroxisome numbers.
      This was not observed in glucose-grown dnm1 cells, but was evident in cells grown
      in the presence of oleate. Similar observations were made in cells lacking Fis1p,
      a protein involved in Dnm1p function. Fluorescence microscopy of cells producing
      Dnm1-GFP or GFP-Fis1p demonstrated that both proteins had a dual localization on
      mitochondria and peroxisomes. Quantitative analysis revealed a greater reduction
      in peroxisome number in oleate-induced vps1 cells relative to dnm1 or fis1 cells.
      A significant fraction of oleate-induced vps1 cells still contained two or more
      peroxisomes. Conversely, almost all cells of a dnm1 vps1 double-deletion strain
      contained only one, enlarged peroxisome. This suggests that deletion of DNM1
      reinforces the vps1 peroxisome phenotype. Time-lapse imaging indicated that
      during budding of dnm1 vps1 cells, the single peroxisome present in the mother
      cell formed long protrusions into the developing bud. This organelle divided at a
      very late stage of the budding process, possibly during cytokinesis.

PMID- 16968747
TI  - Characterization of erasin (UBXD2): a new ER protein that promotes ER-associated
      protein degradation.
AB  - Ubiquitin regulator-X (UBX) is a discrete protein domain that binds p97/valosin
      containing protein (VCP), a molecular chaperone involved in diverse cell
      processes, including endoplasmic-reticulum-associated protein degradation (ERAD).
      Here we characterize a human UBX-containing protein, UBXD2, that is highly
      conserved in mammals, which we have renamed erasin. Biochemical fractionation,
      immunofluorescence and electron microscopy, and protease protection experiments
      suggest that erasin is an integral membrane protein of the endoplasmic reticulum
      and nuclear envelope with both its N- and C-termini facing the cytoplasm or
      nucleoplasm. Localization of GFP-tagged deletion derivatives of erasin in HeLa
      cells revealed that a single 21-amino-acid sequence located near the C-terminus
      is necessary and sufficient for localization of erasin to the endoplasmic
      reticulum. Immunoprecipitation and GST-pulldown experiments confirmed that erasin
      binds p97/VCP via its UBX domain. Additional immunoprecipitation assays indicated
      that erasin exists in a complex with other p97/VCP-associated factors involved in
      ERAD. Overexpression of erasin enhanced the degradation of the ERAD substrate
      CD3delta, whereas siRNA-mediated reduction of erasin expression almost completely
      blocked ERAD. Erasin protein levels were increased by endoplasmic reticulum
      stress. Immunohistochemical staining of brain tissue from patients with
      Alzheimer's disease and control subjects revealed that erasin accumulates
      preferentially in neurons undergoing neurofibrillary degeneration in Alzheimer's
      disease. These results suggest that erasin may be involved in ERAD and in
      Alzheimer's disease.

PMID- 16968748
TI  - Estrogen-receptor-alpha exchange and chromatin dynamics are ligand- and domain
      dependent.
AB  - We report a mammalian-based promoter chromosomal array system developed for
      single-cell studies of transcription-factor function. Designed after the
      prolactin promoter-enhancer, it allows for the direct visualization of estrogen
      receptor alpha (ERalpha) and/or Pit-1 interactions at a physiologically regulated
      transcription locus. ERalpha- and ligand-dependent cofactor recruitment, large
      scale chromatin modifications and transcriptional activity identified a distinct
      fingerprint of responses for each condition. Ligand-dependent transcription (more
      than threefold activation compared with vehicle, or complete repression by mRNA
      fluorescent in situ hybridization) at the array correlated with its state of
      condensation, which was assayed using a novel high throughput microscopy
      approach. In support of the nuclear receptor hit-and-run model, photobleaching
      studies provided direct evidence of very transient ER-array interactions, and
      revealed ligand-dependent changes in k(off). ERalpha-truncation mutants indicated
      that helix-12 and interactions with co-regulators influenced both large-scale
      chromatin modeling and photobleaching recovery times. These data also showed that
      the ERalpha DNA-binding domain was insufficient for array targeting.
      Collectively, quantitative observations from this physiologically relevant
      biosensor suggest stochastic-based dynamics influence gene regulation at the
      promoter level.

PMID- 16968750
TI  - Regulation of the polarity kinases PAR-1/MARK by 14-3-3 interaction and
      phosphorylation.
AB  - Members of the PAR-1/MARK kinase family play critical roles in polarity and cell
      cycle control and are regulated by 14-3-3 scaffolding proteins, as well as the
      LKB1 tumour suppressor kinase and atypical protein kinase C (PKC). In this study,
      we initially investigated the mechanism underlying the interaction of mammalian
      MARK3 with 14-3-3. We demonstrate that 14-3-3 binding to MARK3 is dependent on
      phosphorylation, and necessitates the phosphate-binding pocket of 14-3-3. We
      found that interaction with 14-3-3 was not mediated by the previously
      characterised MARK3 phosphorylation sites, which led us to identify 15 novel
      sites of phosphorylation. Single point mutation of these sites, as well as the
      previously identified LKB1-(T211) and the atypical PKC sites (T564/S619), did not
      disrupt 14-3-3 binding. However, a mutant in which all 17 phosphorylation sites
      had been converted to alanine residues (termed 17A-MARK3), was no longer able to
      bind 14-3-3. Wild-type MARK3 was present in both the cytoplasm and plasma
      membrane, whereas the 17A-MARK3 mutant was strikingly localised at the plasma
      membrane. We provide data indicating that the membrane localisation of MARK3
      required a highly conserved C-terminal domain, which has been termed kinase
      associated domain-1 (KA-1). We also show that dissociation of 14-3-3 from MARK3
      did not affect catalytic activity, and that a MARK3 mutant, which could not
      interact with 14-3-3, was normally active. Finally, we establish that there are
      significant differences in the subcellular localisation of MARK isoforms, as well
      as in the impact that atypical PKC overexpression has on 14-3-3 binding and
      localisation. Collectively, these results indicate that 14-3-3 binding to MARK
      isoforms is mediated by multiple phosphorylation sites, and serves to anchor MARK
      isoforms in the cytoplasm.

PMID- 16968751
TI  - Disasters in the 21st century: lessons from project liberty.

PMID- 16968749
TI  - Dystroglycan loss disrupts polarity and beta-casein induction in mammary
      epithelial cells by perturbing laminin anchoring.
AB  - Precise contact between epithelial cells and their underlying basement membrane
      is crucial to the maintenance of tissue architecture and function. To understand
      the role that the laminin receptor dystroglycan (DG) plays in these processes, we
      assayed cell responses to laminin-111 following conditional ablation of DG gene
      (Dag1) expression in cultured mammary epithelial cells. Strikingly, DG loss
      disrupted laminin-111-induced polarity and beta-casein production, and abolished
      laminin assembly at the step of laminin binding to the cell surface. Dystroglycan
      re-expression restored these deficiencies. Investigations of the mechanism
      revealed that DG cytoplasmic sequences were not necessary for laminin assembly
      and signaling, and only when the entire mucin domain of extracellular DG was
      deleted did laminin assembly not occur. These results demonstrate that DG is
      essential as a laminin-111 co-receptor in mammary epithelial cells that functions
      by mediating laminin anchoring to the cell surface, a process that allows laminin
      polymerization, tissue polarity and beta-casein induction. The observed loss of
      laminin-111 assembly and signaling in Dag1(-/-) mammary epithelial cells provides
      insights into the signaling changes occurring in breast carcinomas and other
      cancers, where the binding function of DG to laminin is frequently defective.

PMID- 16968752
TI  - Project Liberty: New York's crisis counseling program created in the aftermath of
      September 11, 2001.

PMID- 16968753
TI  - Demographic characteristics of individuals who received Project Liberty crisis
      counseling services.
AB  - OBJECTIVES: This article describes demographic characteristics of service
      recipients and their patterns of use of crisis counseling services provided under
      Project Liberty during the 27 months after the September 11, 2001, attacks on the
      World Trade Center. It also examines the extent to which service recipients
      reflected the demographic characteristics of their home communities. METHODS: A
      total of 753,015 service encounter logs submitted by 177 providers were analyzed
      to determine rates of use by different demographic groups and to evaluate
      patterns of use over time with goodness-of-fit and logistic regression models.
      RESULTS: A total of 687,848 individual crisis counseling sessions were provided
      to an estimated 465,428 individuals, including large numbers of persons from
      racial or ethnic minority groups and non-English-speaking individuals. Most of
      these services were provided to residents of the five New York City boroughs,
      with a small percentage of services to residents from the ten surrounding
      counties. Most services were provided in community settings rather than provider
      offices. African-American and Hispanic individuals showed the greatest increase
      in rates of accessing services over time. Follow-up visits were significantly
      more likely to be by Caucasians than by non-Caucasians, and children were more
      likely than adults to receive follow-up visits. Demographic characteristics of
      individuals using Project Liberty crisis counseling services generally were
      representative of the five boroughs and ten other counties constituting the
      greater metropolitan region and representative of estimated need. CONCLUSIONS:
      Project Liberty provided services that were accessible to individuals of diverse
      racial and ethnic backgrounds.

PMID- 16968754
TI  - Use of Project Liberty counseling services over time by individuals in various
      risk categories.
AB  - OBJECTIVE: The authors examined temporal changes in the rates at which people
      sought access to Project Liberty services after the attacks of September 11,
      2001, according to risk category (family of missing or deceased, persons directly
      affected, uniformed personnel, other rescue or recovery workers, schoolchildren,
      displaced employed and unemployed workers, persons with disabilities, and the
      general population). METHODS: First visits to individual counseling services, as
      determined from logs of 465,428 service encounters, were proportioned among risk
      categories and plotted across 27 months. RESULTS: Individuals who lost family
      members accounted for 40 percent of visits in the first month but dropped to 5
      percent or fewer visits by five months. Uniformed personnel used
      disproportionately larger percentages of services after the first year.
      Occupationally displaced and unemployed workers sought counseling at relatively
      steady rates. CONCLUSIONS: Postdisaster counseling should be made available for
      extended periods, with shifting emphases to meet the changing needs of high-risk
      groups.

PMID- 16968755
TI  - Clusters of event reactions among recipients of Project Liberty mental health
      counseling.
AB  - OBJECTIVE: This study aimed to determine a pattern in the frequency with which
      individuals who manifested distress reactions resembling diagnostic syndromes of
      posttraumatic stress disorder (PTSD) and major depressive disorder accessed
      services provided by Project Liberty. METHODS: Hierarchical cluster analysis was
      applied to 31 reactions to stress (event reactions) shown by 465,428 recipients
      of Project Liberty counseling, to determine how well event reactions mapped onto
      traditional diagnostic criteria. Service recipients were tracked when they first
      sought Project Liberty counseling during the 27 months after the attacks. Those
      who reported three or more reactions associated with these clusters were
      characterized as having possible diagnosable conditions. RESULTS: Strong
      consistent clusters corresponding to traumatic stress and depressive symptoms
      emerged, with 26 percent, 16 percent, and 8 percent of service recipients rated
      as having possible PTSD, major depressive disorder, or both, respectively. Taken
      together, this group constituted over 40 percent of service recipients served by
      Project Liberty almost every month throughout the 27 months of its existence.
      CONCLUSIONS: Event reactions, as reported by Project Liberty crisis counselors,
      many of whom were nonclinicians, mapped coherently onto diagnostic syndromes,
      suggesting that a checklist of such reactions may be useful to disaster
      counselors as a cost-effective screening and planning instrument. The steady
      entry over time into Project Liberty counseling by a substantial number of
      individuals experiencing high levels of distress underscores the need for
      providing long-term access to mental health services postdisaster.

PMID- 16968756
TI  - Service utilization and event reaction patterns among children who received
      Project Liberty counseling services.
AB  - OBJECTIVES: This study examined service utilization and event reaction patterns
      among children who used crisis counseling services provided under Project Liberty
      for 27 months after the September 11, 2001, terrorist attacks on the World Trade
      Center. METHODS: The authors analyzed logs of 681,318 service encounters
      submitted by Project Liberty counselors, paying particular attention to
      demographic characteristics and reported event reactions. RESULTS: Nine percent
      of service recipients reached by community-based Project Liberty providers were
      children, whereas census data for the 15 counties and boroughs served by Project
      Liberty indicated that children constituted 25 percent of the population. Service
      use as a function of race or ethnicity and of gender was consistent with census
      data. Similar to findings for adults, the most common emotional event reactions
      reported for children were experiencing sadness and tearfulness, being anxious
      and fearful, having difficulty concentrating, experiencing irritability and
      anger, having intrusive thoughts or images, and having difficulty sleeping.
      Behavioral event reactions listed on service logs suggested that older children
      (12 to 17 years) were more likely to use drugs whereas elementary school-age
      children were more likely to display signs of anxiety, isolation and withdrawal,
      and difficulties with concentration and memory. CONCLUSIONS: Sensitivity to
      differences in the event reaction patterns shown by younger and older children
      may be useful in refining treatments to help reduce the psychological impact of
      children's trauma after terrorist incidents.

PMID- 16968757
TI  - The road back: predictors of regaining preattack functioning among Project
      Liberty clients.
AB  - OBJECTIVES: This study determined the likelihood and predictors of Project
      Liberty counseling recipients' reporting their return to satisfactory life
      functioning 16 to 26 months after the September 11, 2001, attacks. METHODS: Using
      anonymous brief paper-and-pencil questionnaires or structured telephone
      interviews, 452 respondents provided retrospective ratings of their functioning
      in five life domains during the month before the World Trade Center attacks and
      the month immediately before the assessment. Information on demographic
      characteristics and exposure to risk during the World Trade Center attacks also
      was obtained and used in logistic regression models. The 153 respondents who were
      interviewed by telephone also rated helpfulness of various coping strategies.
      RESULTS: In the five domains, 77 to 87 percent of the sample reported good to
      excellent functioning in the month before the attacks; 55 to 68 percent reported
      returning to at least the same level of daily functioning after the attacks.
      African Americans were two to four times more likely than respondents of all
      other races to report a return to good or excellent functioning after the attack
      in four domains. Compared with respondents who did not lose their job as a result
      of the attacks, those who did lose their job were less likely to return to good
      preattack functioning in two domains. Project Liberty counseling reportedly
      helped 90 percent of respondents return to predisaster levels of functioning.
      CONCLUSIONS: Responses to future terrorist attacks should consider demographic
      characteristics and the impact of the attack because they can affect return to
      preattack functioning. Counselors should support activities that facilitate
      positive responses and ameliorate negative psychological responses.

PMID- 16968758
TI  - Screening for complicated grief among Project Liberty service recipients 18
      months after September 11, 2001.
AB  - OBJECTIVE: The authors surveyed a sample of Project Liberty crisis counseling
      recipients approximately 1.5 years after the terrorist attacks on September 11,
      2001, to determine the proportion of respondents who screened positive for
      complicated grief, a recently identified condition marked by symptoms of
      continuing separation distress and accompanying bereavement-related traumatic
      distress. METHODS: A total of 149 service recipients drawn from eight high-volume
      providers responded to a telephone survey that included questions to screen for
      complicated grief. RESULTS: Approximately half of the recipients knew someone who
      had been killed in the attacks. Of those recipients, 44 percent screened positive
      for complicated grief. Individuals who lost a family member were more likely than
      those who lost an acquaintance to screen positive for complicated grief. Positive
      screens were associated with functional impairment independent of the presence of
      symptoms consistent with full or subthreshold major depression or posttraumatic
      stress disorder (PTSD). Thirty-two percent of those who screened positive for
      complicated grief did not meet even subthreshold criteria for major depression or
      PTSD. CONCLUSIONS: Results affirmed the importance of complicated grief as a
      unique condition and indicated the need to attend to the psychological
      consequences of bereavement in disaster-related mental health services.

PMID- 16968759
TI  - Outcomes of enhanced counseling services provided to adults through Project
      Liberty.
AB  - OBJECTIVE: Project Liberty provided brief crisis counseling to 753,015 residents
      of New York City and surrounding counties after the attacks on the World Trade
      Center. Most regained predisaster functioning after counseling. For those who did
      not, Project Liberty provided enhanced services by specially trained, licensed
      mental health professionals. Individuals receiving crisis counseling and enhanced
      services responded to confidential telephone interviews about 18 and 24 months,
      respectively, after the attacks. Impairment was compared between groups to
      determine whether enhanced services recipients reported improved functioning and
      fewer symptoms of depression, posttraumatic stress, and complicated grief.
      METHODS: Crisis counseling recipients (N=153) were interviewed once and enhanced
      services recipients (N=76) were interviewed twice about symptomatology and daily
      functioning. RESULTS: The samples did not differ in age or gender. Significantly
      greater proportions of enhanced services recipients reported knowing someone who
      died as a result of the attacks, having been involved in rescue efforts, or
      having lost their job because of the attacks. Compared with crisis counseling
      respondents, enhanced services recipients at their first interview reported
      significantly more symptoms of depression, grief, and traumatic stress and
      significantly poorer daily functioning in five life areas. At follow-up, enhanced
      services respondents reported significant improvement in three of five
      functioning domains, significantly fewer symptoms of depression and grief, and
      marginally less traumatic stress. CONCLUSIONS: Recipients of enhanced services
      were more impaired than people who received only crisis counseling. On the basis
      of reports from service recipients, meaningful improvements in functioning and
      symptoms may be associated with the receipt of enhanced services.

PMID- 16968761
TI  - Did Project Liberty displace community-based medicaid services in New York?
AB  - OBJECTIVE: This study analyzed how the introduction of Project Liberty services
      after the September 11, 2001, terrorist attacks affected agencies' provision of
      community-based Medicaid mental health services in the New York metropolitan
      area. METHODS: Provision of Medicaid mental health services was tracked between
      January 2000 and June 2003 for provider agencies participating in Project Liberty
      (N=164) and for a comparison group of mental health provider agencies that did
      not participate in this program (N=94). RESULTS: Overall, participation in
      Project Liberty did not significantly affect the volume of Medicaid services
      provided. However, for agencies with one site, a statistically significant
      difference was seen; compared with agencies in the comparison group, agencies
      that participated in Project Liberty claimed a mean+/-SE decrease of $4.66+/-3.57
      less in Medicaid services per month per Project Liberty visit. CONCLUSIONS:
      Project Liberty permitted rapid expansion of the total volume of services
      provided by community-based organizations without interfering with the provision
      of traditional services, although a modest effect was seen for smaller agencies.
      Although the results do not imply that "supply side" planning for disaster needs
      would not improve system response, they do imply that implementation of flexible
      "demand side" financing can call forth a large volume of new services rapidly and
      without interfering with other community services.

PMID- 16968760
TI  - Impact of a media campaign for disaster mental health counseling in post
      September 11 New York.
AB  - OBJECTIVE: After the September 11, 2001, terrorist attacks on the World Trade
      Center, the New York State Office of Mental Health (NYOMH) initiated a three
      phase multifaceted, multilingual media campaign that advertised the availability
      of counseling services. This study evaluated the association between patterns of
      spending within this campaign and the volume of calls received and referred to a
      counseling program. METHODS: Spending on television, radio, print, and other
      advertising was examined, as was the corresponding volume of calls to the NetLife
      hotline seeking referrals to counseling services. RESULTS: From September 2001 to
      December 2002, $9.38 million was spent on Project Liberty media campaigns. Call
      volumes increased during months when total monthly expenditures peaked.
      Initially, flyers, billboards, and other material items accounted for most
      monthly expenses. Over time, spending for television and radio advertisements
      increased, whereas other advertising declined. Temporal patterns show that in
      periods after an increase in media spending, call volumes increased independently
      of other sentinel events such as the one-year anniversary of the attacks.
      CONCLUSIONS: Sustained advertising through multiple media outlets appeared to be
      effective in encouraging individuals to seek mental health services.

PMID- 16968762
TI  - Characteristics of Project Liberty clients that predicted referrals to intensive
      mental health services.
AB  - OBJECTIVE: The authors describe characteristics of Project Liberty crisis
      counseling recipients that predicted referral to more intensive professional
      mental health treatments over the two-year period after the terrorist attacks on
      the World Trade Center. METHODS: Random-effects ordinal regression models were
      applied to data from 684,500 logs of Project Liberty service encounters for
      individual counseling sessions. RESULTS: Overall, about 9 percent of individual
      counseling visits ended with a referral to professional mental health services.
      Individuals needing intensive mental health treatment continued to enter Project
      Liberty for two years after the World Trade Center attacks. The strongest
      predictor of referral was having reactions to the attack that fell into a greater
      number of the four domains assessed-behavioral, emotional, physical, or cognitive
      domains. Individuals with reactions in four domains were most likely to be
      referred. Those who had greater attack-related exposure were also more likely to
      be referred. CONCLUSIONS: It is important to provide long-term access to brief
      counseling and triage services and to target these interventions specifically to
      individuals displaying greater distress or impairment and having more traumatic
      exposure.

PMID- 16968763
TI  - Clients' satisfaction with Project Liberty counseling services.
AB  - OBJECTIVE: Satisfaction with 11 aspects of service quality and four domains of
      effectiveness was assessed for counseling services offered through Project
      Liberty after the September 11, 2001, attacks on the World Trade Center. METHODS:
      A total of 607 Project Liberty service recipients completed anonymous
      questionnaires, telephone interviews, or both. The 11 aspects of quality were
      counselor respect for client, willingness to listen, cultural sensitivity,
      speaking the same language as the client, amount of counseling time, convenience
      of meeting time and location, information received, whether the service would be
      used again, whether the service would be recommended to friends or family, and
      overall quality of service. The four effectiveness domains were daily
      responsibilities, relationships, physical health, and community involvement.
      RESULTS: At least 89 percent of service recipients rated Project Liberty as
      either good or excellent across 11 service quality dimensions and four
      effectiveness domains. The counselor's respect for clients and his or her
      cultural sensitivity were rated particularly favorably. CONCLUSIONS: These
      ratings suggest that, from the viewpoint of these recipients of counseling
      services, Project Liberty counselors were largely successful in providing
      accessible, acceptable, and useful services after the World Trade Center
      disaster. Such evaluations can be conducted in a cost-effective manner and
      integrated with evidence-based practice to ultimately ensure that recipients of
      counseling receive the most efficient and effective interventions.

PMID- 16968764
TI  - Use of clients' self-reports to monitor Project Liberty clinicians' fidelity to a
      cognitive-behavioral intervention.
AB  - OBJECTIVE: This study examined outcomes associated with clinicians' fidelity to
      key elements of a cognitive-behavioral treatment intervention developed for
      Project Liberty's enhanced services counseling program. METHODS: In telephone
      interviews 60 individuals reported how often their clinicians provided six
      components considered central to the intervention by the intervention developers.
      Respondents received services at sites where some (25 to 50 percent) or all
      clinicians had received training in the intervention. RESULTS: Compared with
      respondents who received services where only some clinicians had received
      training (N=19), those who received services where all clinicians had received
      training (N=41) were significantly more likely to report that their clinicians
      applied techniques central to the intervention (p<.01). Additionally, those who
      received services from sites where all clinicians were trained were significantly
      more likely to report that they had been given homework (p<.05). CONCLUSIONS:
      Brief questions to service recipients are a useful and cost-effective way to
      monitor intervention fidelity.

PMID- 16968765
TI  - Effectiveness of two methods of obtaining feedback on mental health services
      provided to anonymous recipients.
AB  - OBJECTIVE: The authors examined alternative methods for obtaining feedback from
      people receiving anonymous mental health services via Project Liberty, an
      initiative that provided free counseling to residents of the New York City area
      after the 2001 attacks on the World Trade Center. METHODS: Counselors offered all
      English-speaking and Spanish-speaking adults who used Project Liberty crisis
      counseling services the opportunity to evaluate Project Liberty via a telephone
      interview (eight sites) or a brief questionnaire (four sites). RESULTS: A total
      of 107 service recipients provided feedback via a brief 32-item questionnaire,
      and 153 gave feedback via a 45-minute telephone interview. Although the overall
      participation rates were modest (less than 20 percent), nearly three-quarters of
      those who volunteered to participate in the telephone interview (for which they
      received $20) did so. Neither gender nor racial or ethnic group was associated
      with a greater likelihood of participating in one method over another.
      CONCLUSIONS: Responses to items on the brief questionnaire and in the telephone
      interview were similar, and offering multiple response methods increased
      participation rates. Although telephone interviews were more costly than the
      questionnaire to administer, they provided important additional information about
      ongoing symptoms and problems that individuals experienced after the attacks. The
      modest response rates obtained in the evaluation indicate that future evaluations
      of postdisaster services need to use methodstomaximizeresponse rates and provider
      adherence to administrative tasks that are critical to the evaluation.

PMID- 16968766
TI  - A psychometric analysis of Project Liberty's adult enhanced services referral
      tool.
AB  - OBJECTIVES: Project Liberty was the first federally funded crisis counseling
      program to offer evidence-informed treatments to crisis counseling recipients in
      need of more intensive clinical intervention. The Adult Enhanced Services
      Referral Tool was developed as a screening instrument for making and monitoring
      referrals to enhanced services. This study aimed to examine how well the tool
      functioned for identifying persons who would perceive a need for professional
      treatment. METHODS: A one-page tool was created that assessed demographic
      characteristics, risk categories, and psychological reactions to the focal event,
      September 11, 2001. Psychosocial reactions were assessed by the 12-item SPRINT-E,
      which is an expanded version of the Short Post-Traumatic Stress Disorder Rating
      Interview (SPRINT). The SPRINT-E was embedded in the Adult Enhanced Services
      Referral Tool. Data were collected from 788 clients who received crisis
      counseling between June and October 2003. RESULTS: The SPRINT-E is a
      unidimensional measure of distress and dysfunction. Internal consistency was
      excellent for the total sample (alpha=.93) and subsamples. Among the 543 clients
      offered referral, 71 percent accepted. Among those offered referral, the number
      of intense reactions (score of 4, quite a bit, or 5, very much) was by far the
      strongest predictor of referral acceptance. CONCLUSIONS: The SPRINT-E was
      successfully integrated into the crisis counseling program and provided an
      apparently successful, empirical basis for referral from counseling to
      professional treatment. Results of the brief psychological assessment provided a
      stronger basis for referral to treatment than membership in a risk category (for
      example, family member of deceased) alone.

PMID- 16968767
TI  - A mental health program for ground zero rescue and recovery workers: cases and
      observations.
AB  - Clinical vignettes from the World Trade Center Worker and Volunteer Mental Health
      Monitoring and Treatment Program at the Mount Sinai Medical Center in New York
      City are presented. The hospital-based program pairs mental health screenings
      with federally funded occupational medical screenings to identify persons with
      mental health problems related to their rescue and recovery roles. The program
      also provides on-site mental health treatment. The cases illustrate the diverse
      mental health needs of the rescue and recovery workers, some of whom initially
      sought treatment years after September 11, 2001. The cases show that in addition
      to symptoms of posttraumatic stress disorder, workers experienced survivor guilt,
      distressing memories of childhood trauma, shame associated with intense feelings,
      substance abuse relapse, psychosis, and problems with family relationships.

PMID- 16968768
TI  - News coverage analyses of mental health services immediately after September 11,
      2001.
AB  - OBJECTIVE: This study examined news coverage of mental health resources after the
      attacks of September 11, 2001, in order to inform mental health disaster planning
      and response. METHODS: Keyword searches resulted in a random sample of stories
      reported in the United States between September 11 and 25, 2001. A total of
      10,428 stories combining attack and mental health terms were gathered, and a
      sample of 438 articles that mentioned mental health formed the basis of this
      content analysis. RESULTS: Of the 438 reports in the nationwide sample, 35 (8
      percent) identified at least one risk factor for developing emotional problems
      after the attacks, 204 (47 percent) described at least one coping mechanism, 25
      (6 percent) provided contact information for support, and 97 (22 percent) cited
      expert sources. CONCLUSIONS: This exploratory study suggests a need to evaluate
      and improve the dissemination of mental health information to help the public
      cope in the aftermath of disasters.

PMID- 16968769
TI  - Continuous up-regulation of heat shock proteins in larvae, but not adults, of a
      polar insect.
AB  - Antarctica's terrestrial environment is a challenge to which very few animals
      have adapted. The largest, free-living animal to inhabit the continent year-round
      is a flightless midge, Belgica antarctica. Larval midges survive the lengthy
      austral winter encased in ice, and when the ice melts in summer, the larvae
      complete their 2-yr life cycle, and the wingless adults form mating aggregations
      while subjected to surprisingly high substrate temperatures. Here we report a
      dichotomy in survival strategies exploited by this insect at different stages of
      its life cycle. Larvae constitutively up-regulate their heat shock proteins
      (small hsp, hsp70, and hsp90) and maintain a high inherent tolerance to
      temperature stress. High or low temperature exposure does not further up-regulate
      these genes nor does it further enhance thermotolerance. Such "preemptive"
      synthesis of hsps is sufficient to prevent irreversible protein aggregation in
      response to a variety of common environmental stresses. Conversely, adults
      exhibit no constitutive up-regulation of their hsps and have a lower intrinsic
      tolerance to high temperatures, but their hsps can be thermally activated,
      resulting in enhanced thermotolerance. Thus, the midge larvae, but not the
      adults, have adopted the unusual strategy of expressing hsps continuously,
      possibly to facilitate proper protein folding in a cold habitat that is more
      thermally stable than that of the adults but a habitat subjected frequently to
      freeze-thaw episodes and bouts of pH, anoxic, and osmotic stress.

PMID- 16968770
TI  - The nucleotide-binding site of bacterial translation initiation factor 2 (IF2) as
      a metabolic sensor.
AB  - Translational initiation factor 2 (IF2) is a guanine nucleotide-binding protein
      that can bind guanosine 3',5'-(bis) diphosphate (ppGpp), an alarmone involved in
      stringent response in bacteria. In cells growing under optimal conditions, the
      GTP concentration is very high, and that of ppGpp very low. However, under stress
      conditions, the GTP concentration may decline by as much as 50%, and that of
      ppGpp can attain levels comparable to those of GTP. Here we show that IF2 binds
      ppGpp at the same nucleotide-binding site and with similar affinity as GTP. Thus,
      GTP and the alarmone ppGpp can be considered two alternative physiologically
      relevant IF2 ligands. ppGpp interferes with IF2-dependent initiation complex
      formation, severely inhibits initiation dipeptide formation, and blocks the
      initiation step of translation. Our data suggest that IF2 has the properties of a
      cellular metabolic sensor and regulator that oscillates between an active GTP
      bound form under conditions allowing active protein syntheses and an inactive
      ppGpp-bound form when shortage of nutrients would be detrimental, if not
      accompanied by slackening of this synthesis.

PMID- 16968771
TI  - Functional organization of perisylvian activation during presentation of
      sentences in preverbal infants.
AB  - We examined the functional organization of cerebral activity in 3-month-old
      infants when they were listening to their mother language. Short sentences were
      presented in a slow event-related functional MRI paradigm. We then parsed the
      infant's network of perisylvian responsive regions into functionally distinct
      regions based on their speed of activation and sensitivity to sentence
      repetition. An adult-like structure of functional MRI response delays was
      observed along the superior temporal regions, suggesting a hierarchical
      processing scheme. The fastest responses were recorded in the vicinity of
      Heschl's gyrus, whereas responses became increasingly slower toward the posterior
      part of the superior temporal gyrus and toward the temporal poles and inferior
      frontal regions (Broca's area). Activation in the latter region increased when
      the sentence was repeated after a 14-s delay, suggesting the early involvement of
      Broca's area in verbal memory. The fact that Broca's area is active in infants
      before the babbling stage implies that activity in this region is not the
      consequence of sophisticated motor learning but, on the contrary, that this
      region may drive, through interactions with the perceptual system, the learning
      of the complex motor sequences required for future speech production. Our results
      point to a complex, hierarchical organization of the human brain in the first
      months of life, which may play a crucial role in language acquisition in our
      species.

PMID- 16968772
TI  - A molecular mechanism for osmolyte-induced protein stability.
AB  - Osmolytes are small organic compounds that affect protein stability and are
      ubiquitous in living systems. In the equilibrium protein folding reaction,
      unfolded (U) native (N), protecting osmolytes push the equilibrium toward N,
      whereas denaturing osmolytes push the equilibrium toward U. As yet, there is no
      universal molecular theory that can explain the mechanism by which osmolytes
      interact with the protein to affect protein stability. Here, we lay the
      groundwork for such a theory, starting with a key observation: the transfer free
      energy of protein backbone from water to a water/osmolyte solution, Deltagtr, is
      negatively correlated with an osmolyte's fractional polar surface area. Deltagtr
      measures the degree to which an osmolyte stabilizes a protein. Consequently, a
      straightforward interpretation of this correlation implies that the interaction
      between the protein backbone and osmolyte polar groups is more favorable than the
      corresponding interaction with nonpolar groups. Such an interpretation
      immediately suggests the existence of a universal mechanism involving osmolyte,
      backbone, and water. We test this idea by using it to construct a quantitative
      solvation model in which backbone/solvent interaction energy is a function of
      interactant polarity, and the number of energetically equivalent ways of
      realizing a given interaction is a function of interactant surface area. Using
      this model, calculated Deltagtr values show a strong correlation with measured
      values (R = 0.99). In addition, the model correctly predicts that
      protecting/denaturing osmolytes will be preferentially excluded/accumulated
      around the protein backbone. Taken together, these model-based results
      rationalize the dominant interactions observed in experimental studies of
      osmolyte-induced protein stabilization and denaturation.

PMID- 16968773
TI  - Protein surface hydration mapped by site-specific mutations.
AB  - Water motion at protein surfaces is fundamental to protein structure, stability,
      dynamics, and function. By using intrinsic tryptophans as local optical probes,
      and with femtosecond resolution, it is possible to probe surface-water motions in
      the hydration layer. Here, we report our studies of local hydration dynamics at
      the surface of the enzyme Staphylococcus nuclease using site-specific mutations.
      From these studies of the WT and four related mutants, which change local charge
      distribution and structure, we are able to ascertain the contribution to
      solvation by protein side chains as relatively insignificant. We determined the
      time scales of hydration to be 3-5 ps and 100-150 ps. The former is the result of
      local librational/rotational motions of water near the surface; the latter is a
      direct measure of surface hydration assisted by fluctuations of the protein.
      Experimentally, these hydration dynamics of the WT and the four mutants are also
      consistent with results of the total dynamic Stokes shifts and fluorescence
      emission maxima and are correlated with their local charge distribution and
      structure. We discuss the role of protein fluctuation on the time scale of labile
      hydration and suggest reexamination of recent molecular dynamics simulations.

PMID- 16968774
TI  - Evolving resistance to obesity in an insect.
AB  - Failure to adapt to a changing nutritional environment comes at a cost, as
      evidenced by the modern human obesity crisis. Consumption of energy-rich diets
      can lead to obesity and is associated with deleterious consequences not only in
      humans but also in many other animals, including insects. The question thus
      arises whether animals restricted over multiple generations to high-energy diets
      can evolve mechanisms to limit the deposition of adverse levels of body fat. We
      show that Plutella xylostella caterpillars reared for multiple generations on
      carbohydrate-rich foods (either a chemically defined artificial diet or a high
      starch Arabidopsis mutant) progressively developed the ability to eat excess
      carbohydrate without laying it down as fat, providing strong evidence that excess
      fat storage has a fitness cost. In contrast, caterpillars reared in carbohydrate
      scarce environments (a chemically defined artificial diet or a low-starch
      Arabidopsis mutant) had a greater propensity to store ingested carbohydrate as
      fat. Additionally, insects reared on the low-starch Arabidopsis mutant evolved a
      preference for laying their eggs on this plant, whereas those selected on the
      high-starch Arabidopsis mutant showed no preference. Our results provide an
      experimental example of metabolic adaptation in the face of changes in the
      nutritional environment and suggest that changes in plant macronutrient profiles
      may promote host-associated population divergence.

PMID- 16968775
TI  - Hedgehog modulates cell cycle regulators in stem cells to control hematopoietic
      regeneration.
AB  - The signals that control the regenerative ability of hematopoietic stem cells
      (HSCs) in response to damage are unknown. Here, we demonstrate that downstream
      activation of the Hedgehog (Hh) signaling pathway induces cycling and expansion
      of primitive bone marrow hematopoietic cells under homeostatic conditions and
      during acute regeneration. However, this effect is at the expense of HSC
      function, because continued Hh activation during regeneration represses
      expression of specific cell cycle regulators, leading to HSC exhaustion. In vivo
      treatment with an inhibitor of the Hh pathway rescues these transcriptional and
      functional defects in HSCs. Our study establishes Hh signaling as a regulator of
      the HSC cell cycle machinery that balances hematopoietic homeostasis and
      regeneration in vivo.

PMID- 16968776
TI  - A phosphoryl transfer intermediate in the GTPase reaction of Ras in complex with
      its GTPase-activating protein.
AB  - The hydrolysis of nucleoside triphosphates by enzymes is used as a regulation
      mechanism in key biological processes. Here, the GTP hydrolysis of the protein
      complex of Ras with its GTPase-activating protein is monitored at atomic
      resolution in a noncrystalline state by time-resolved FTIR spectroscopy. At 900
      ms, after the attack of water at the gamma-phosphate, there appears a H2PO4-
      intermediate that is shown to be hydrogen-bonded in an eclipsed conformation to
      the beta-phosphate of GDP. The H2PO4- intermediate is in a position where it can
      either reform GTP or be released from the protein in 7 s in the rate-limiting
      step of the GTPase reaction. We propose that such an intermediate also occurs in
      other GTPases and ATPases.

PMID- 16968777
TI  - Central peptidergic ensembles associated with organization of an innate behavior.
AB  - At the end of each developmental stage, insects perform the ecdysis sequence, an
      innate behavior necessary for shedding the old cuticle. Ecdysis triggering
      hormones (ETHs) initiate these behaviors through direct actions on the CNS. Here,
      we identify the ETH receptor (ETHR) gene in the moth Manduca sexta, which encodes
      two subtypes of GPCR (ETHR-A and ETHR-B). Expression of ETHRs in the CNS
      coincides precisely with acquisition of CNS sensitivity to ETHs and behavioral
      competence. ETHR-A occurs in diverse networks of neurons, producing both
      excitatory and inhibitory neuropeptides, which appear to be downstream signals
      for behavior regulation. These peptides include allatostatins, crustacean
      cardioactive peptide (CCAP), calcitonin-like diuretic hormone, CRF-like diuretic
      hormones (DHs) 41 and 30, eclosion hormone, kinins, myoinhibitory peptides
      (MIPs), neuropeptide F, and short neuropeptide F. In particular, cells L(3,4) in
      abdominal ganglia coexpress kinins, DH41, and DH30, which together elicit the
      fictive preecdysis rhythm. Neurons IN704 in abdominal ganglia coexpress CCAP and
      MIPs, whose joint actions initiate the ecdysis motor program. ETHR-A also is
      expressed in brain ventromedial cells, whose release of EH increases excitability
      in CCAP/MIP neurons. These findings provide insights into how innate, centrally
      patterned behaviors can be orchestrated via recruitment of peptide cotransmitter
      neurons.

PMID- 16968778
TI  - A conserved role for a GATA transcription factor in regulating epithelial innate
      immune responses.
AB  - Innate immunity is an ancient and conserved defense mechanism. Although host
      responses toward various pathogens have been delineated, how these responses are
      orchestrated in a whole animal is less understood. Through an unbiased genome
      wide study performed in Caenorhabditis elegans, we identified a conserved
      function for endodermal GATA transcription factors in regulating local epithelial
      innate immune responses. Gene expression and functional RNAi-based analyses
      identified the tissue-specific GATA transcription factor ELT-2 as a major
      regulator of an early intestinal protective response to infection with the human
      bacterial pathogen Pseudomonas aeruginosa. In the adult worm, ELT-2 is required
      specifically for infection responses and survival on pathogen but makes no
      significant contribution to gene expression associated with intestinal
      maintenance or to resistance to cadmium, heat, and oxidative stress. We further
      demonstrate that this function is conserved, because the human endodermal
      transcription factor GATA6 has a protective function in lung epithelial cells
      exposed to P. aeruginosa. These findings expand the repertoire of innate immunity
      mechanisms and illuminate a yet-unknown function of endodermal GATA proteins.

PMID- 16968780
TI  - Self-assembled single-crystal silicon circuits on plastic.
AB  - We demonstrate the use of self-assembly for the integration of freestanding
      micrometer-scale components, including single-crystal, silicon field-effect
      transistors (FETs) and diffusion resistors, onto flexible plastic substrates.
      Preferential self-assembly of multiple microcomponent types onto a common
      platform is achieved through complementary shape recognition and aided by
      capillary, fluidic, and gravitational forces. We outline a microfabrication
      process that yields single-crystal, silicon FETs in a freestanding, powder-like
      collection for use with self-assembly. Demonstrations of self-assembled FETs on
      plastic include logic inverters and measured electron mobility of 592 cm2/V-s.
      Finally, we extend the self-assembly process to substrates each containing 10,000
      binding sites and realize 97% self-assembly yield within 25 min for 100-microm
      sized elements. High-yield self-assembly of micrometer-scale functional devices
      as outlined here provides a powerful approach for production of macroelectronic
      systems.

PMID- 16968779
TI  - The transcriptome of human oocytes.
AB  - The identification of genes and deduced pathways from the mature human oocyte can
      help us better understand oogenesis, folliculogenesis, fertilization, and
      embryonic development. Human metaphase II oocytes were used within minutes after
      removal from the ovary, and its transcriptome was compared with a reference
      sample consisting of a mixture of total RNA from 10 different normal human
      tissues not including the ovary. RNA amplification was performed by using a
      unique protocol. Affymetrix Human Genome U133 Plus 2.0 GeneChip arrays were used
      for hybridizations. Compared with reference samples, there were 5,331 transcripts
      significantly up-regulated and 7,074 transcripts significantly down-regulated in
      the oocyte. Of the oocyte up-regulated probe sets, 1,430 have unknown function. A
      core group of 66 transcripts was identified by intersecting significantly up
      regulated genes of the human oocyte with those from the mouse oocyte and from
      human and mouse embryonic stem cells. GeneChip array results were validated using
      RT-PCR in a selected set of oocyte-specific genes. Within the up-regulated probe
      sets, the top overrepresented categories were related to RNA and protein
      metabolism, followed by DNA metabolism and chromatin modification. This report
      provides a comprehensive expression baseline of genes expressed in in vivo
      matured human oocytes. Further understanding of the biological role of these
      genes may expand our knowledge on meiotic cell cycle, fertilization, chromatin
      remodeling, lineage commitment, pluripotency, tissue regeneration, and
      morphogenesis.

PMID- 16968781
TI  - Forced and unforced ocean temperature changes in Atlantic and Pacific tropical
      cyclogenesis regions.
AB  - Previous research has identified links between changes in sea surface temperature
      (SST) and hurricane intensity. We use climate models to study the possible causes
      of SST changes in Atlantic and Pacific tropical cyclogenesis regions. The
      observed SST increases in these regions range from 0.32 degrees C to 0.67 degrees
      C over the 20th century. The 22 climate models examined here suggest that century
      timescale SST changes of this magnitude cannot be explained solely by unforced
      variability of the climate system. We employ model simulations of natural
      internal variability to make probabilistic estimates of the contribution of
      external forcing to observed SST changes. For the period 1906-2005, we find an
      84% chance that external forcing explains at least 67% of observed SST increases
      in the two tropical cyclogenesis regions. Model "20th-century" simulations, with
      external forcing by combined anthropogenic and natural factors, are generally
      capable of replicating observed SST increases. In experiments in which forcing
      factors are varied individually rather than jointly, human-caused changes in
      greenhouse gases are the main driver of the 20th-century SST increases in both
      tropical cyclogenesis regions.

PMID- 16968782
TI  - beta-Arrestin2 mediates nephrin endocytosis and impairs slit diaphragm integrity.
AB  - beta-Arrestins mediate internalization of plasma membrane receptors. Nephrin, a
      structural component of the glomerular slit diaphragm, is a single transmembrane
      spanning receptor and belongs to the family of adhesion molecules. Its mutation
      causes a hereditary nephrotic syndrome. We report the previously undescribed
      interaction of beta-arrestin2 with the nephrin C terminus. The phosphorylation
      status of nephrin Y1193 regulates inversely the binding of beta-arrestin2 and
      podocin. The Src-family member Yes, known to enhance podocin-nephrin interaction
      by nephrin phosphorylation, diminishes beta-arrestin2-nephrin interaction. beta
      Arrestin2 induces nephrin endocytosis and attenuates nephrin signaling. This
      finding suggests that nephrin Y1193 serves as a molecular switch that determines
      the integrity of the slit diaphragm by functional competition between beta
      arrestin2 and podocin. This concept offers a molecular pathomechanism of slit
      diaphragm distortion and opens therapeutic avenues for glomerular diseases.

PMID- 16968783
TI  - Pathogenesis and treatment of autosomal-dominant nephrogenic diabetes insipidus
      caused by an aquaporin 2 mutation.
AB  - Frame-shift mutations within the C terminus of aquaporin 2 (AQP2) cause autosomal
      dominant nephrogenic diabetes insipidus (AD-NDI). To identify the molecular
      mechanism(s) of this disease in vivo and to test possible therapeutic strategies,
      we generated a mutant AQP2 (763-772 del) knockin mouse. Heterozygous knockin mice
      showed a severely impaired urine-concentrating ability. However, they were able
      to slightly increase urine osmolality after dehydration. This milder phenotype,
      when compared with autosomal-recessive NDI, is a feature of AD-NDI in humans,
      thus suggesting successful establishment of an AD-NDI mouse model.
      Immunofluorescence of collecting duct cells in the AD-NDI mouse revealed that the
      mutant AQP2 was missorted to the basolateral instead of apical plasma membrane.
      Furthermore, the mutant AQP2 formed a heterooligomer with wild-type AQP2 and
      showed a dominant-negative effect on the normal apical sorting of wild-type AQP2
      even under dehydration. Using this knockin mouse, we tested several drugs for
      treatment of AD-NDI and found that rolipram, a phosphodiesterase 4 inhibitor, was
      able to increase urine osmolality. Phosphodiesterase inhibitors may thus be
      useful drugs for the treatment of AD-NDI. This animal model demonstrates that a
      mutant monomer gains a dominant-negative effect that reverses the normal
      polarized sorting of multimers.

PMID- 16968784
TI  - Mechanisms of uropathogenic Escherichia coli persistence and eradication from the
      urinary tract.
AB  - Recurrent urinary tract infections (rUTIs) are a source of considerable morbidity
      in women. The infecting bacteria in both rUTIs and a de novo acute infection have
      been thought to originate from an extraurinary location. Here, we show in a
      murine model of UTI that uropathogenic Escherichia coli (UPEC) established
      quiescent intracellular reservoirs (QIRs) in Lamp1+ endosomes within the urinary
      bladder epithelium. Depending on the integrity of the urothelial barriers at the
      time of initial infection, these QIRs were established within terminally
      differentiated superficial facet cells and/or underlying transitional epithelial
      cells. Treatment of infected bladders harboring exclusively superficial facet
      cell QIRs with the cationic protein, protamine sulfate, led to epithelial
      exfoliation and eradication of bacteria in 100% of treated animals. However, when
      the bacterial QIRs were harbored in underlying transitional cells, stimulation of
      epithelial turnover triggered reemergence of viable organisms and recurrence of
      infection. Thus, our results suggest (i) that bacterial QIRs within the bladder
      may be a previously unappreciated source of recurrent UTIs and (ii) that inducing
      epithelial exfoliation may be a therapeutic avenue for treating this heretofore
      recalcitrant disease.

PMID- 16968785
TI  - Identifying regulatory mechanisms using individual variation reveals key role for
      chromatin modification.
AB  - Sequence polymorphisms affect gene expression by perturbing the complex network
      of regulatory interactions. We propose a probabilistic method, called Geronemo,
      which directly aims to identify the mechanism by which genetic changes perturb
      the regulatory network. Geronemo automatically constructs a set of coregulated
      genes (modules), whose regulation can involve both sequence variations and
      expression of regulators. By exploiting the modularity of genetic regulatory
      systems, Geronemo reveals regulatory relationships that are indiscernible when
      genes are considered in isolation, allowing the recovery of intricate
      combinatorial regulation. By incorporating both expression and genotype of
      regulators, Geronemo captures cases where the effect of sequence variation on its
      targets is indirect. We applied Geronemo to a data set from the progeny generated
      by a cross between laboratory BY4716 (BY) and wild RM11-1a (RM) isolates of
      Saccharomyces cerevisiae. Geronemo produced previously undescribed hypotheses
      regarding genetic perturbations in the yeast regulatory network, including
      transcriptional regulation, signal transduction, and chromatin modification. In
      particular, we find a large number of modules that have both chromosomal
      characteristics and are regulated by chromatin modification proteins. Indeed, a
      large fraction of the variance in the expression can be explained by a small
      number of markers associated with chromatin modifiers. Additional analysis
      reveals positive selection for sequence evolution of elements in the Swi/Snf
      chromatin remodeling complex. Overall, our results suggest that a significant
      part of individual expression variation in yeast arises from evolution of a small
      number of chromatin structure modifiers.

PMID- 16968786
TI  - Predicting the epidemiological impact of antiretroviral allocation strategies in
      KwaZulu-Natal: the effect of the urban-rural divide.
AB  - Antiretroviral therapy (ART) is becoming available in South Africa. Demand will
      exceed supply; thus, difficult decisions will have to be made in allocating ART.
      The majority of those treated for HIV are likely to be in cities, because health
      infrastructure and personnel are concentrated in urban centers. We predict the
      epidemiological impact of drug allocation strategies (DAS) by using a spatially
      explicit model that links urban and rural epidemics. We parameterize our model by
      using data from the KwaZulu-Natal province in South Africa. We model the South
      African government's treatment plan from 2004-2008, and we predict the
      consequences of one DAS that allocates drugs only to Durban and of two DAS that
      allocate drugs to both urban and rural areas. All three strategies would treat
      500,000 people by 2008. Not surprisingly, the Durban-only DAS would prevent the
      greatest number of infections (an additional 15,000 infections by 2008). However,
      it may have been expected that this DAS would generate the highest levels of
      transmitted resistance, because it concentrates ART in one location.
      Paradoxically, we found that this DAS would generate the lowest levels of
      transmitted resistance. Concentrating treatment in Durban would also avert the
      greatest number of AIDS-related deaths. We discuss the difference between using
      the principle of treatment equity versus using the principle of
      utilitarianism/efficiency to allocate ART. Decisions about allocating scarce
      drugs should consider treatment equity as well as epidemiological consequences.
      Notably, a Durban-only DAS would lead to new disparities in healthcare between
      urban and rural areas in KwaZulu-Natal.

PMID- 16968787
TI  - QnAs with Karl Mahlburg. Interview by Regina Nuzzo.

PMID- 16968788
TI  - Influences of age, gender, smoking, and family history on autoimmune thyroid
      disease phenotype.
AB  - CONTEXT: Both genetic and environmental factors contribute to susceptibility to
      Graves' disease (GD) and Hashimoto's thyroiditis (HT), as well as disease
      manifestations. OBJECTIVE: The objective of the study was to define how
      endogenous/environmental factors contribute to variation in phenotype.
      DESIGN/SETTING: This was a multicenter cohort study. PATIENTS/OUTCOME MEASURES:
      We prospectively collected clinical/biochemical data as part of the protocol for
      a United Kingdom DNA collection for GD and HT. We investigated, in 2805 Caucasian
      subjects, whether age at diagnosis, gender, family history (FH), smoking history,
      and presence of goiter influenced disease manifestations. RESULTS: For 2405
      subjects with GD, the presence of goiter was independently associated with
      disease severity (serum free T4 at diagnosis) (P < 0.001). Free T4 (P < 0.05) and
      current smoking (P < 0.001) were both independent predictors of the presence of
      ophthalmopathy. Approximately half of those with GD (47.4% of females, 40.0% of
      males) and HT (n = 400) (56.4% of females, 51.7% of males) reported a FH of
      thyroid dysfunction. In GD, a FH of hyperthyroidism in any relative was more
      frequent than hypothyroidism (30.1 vs. 24.4% in affected females, P < 0.001). In
      HT, a FH of hypothyroidism was more common than hyperthyroidism (42.1 vs. 22.8%
      in affected females, P < 0.001). For GD (P < 0.001) and HT (P < 0.05), a FH was
      more common in maternal than paternal relatives. The reporting of a parent with
      thyroid dysfunction (hyper or hypo) was associated with lower median age at
      diagnosis of both GD (mother with hyperthyroidism, P < 0.001) and HT (father with
      hypothyroidism, P < 0.05). In GD and HT, there was an inverse relationship
      between the number of relatives with thyroid dysfunction and age at diagnosis (P
      < 0.01). CONCLUSIONS: Marked associations among age at diagnosis, disease
      severity, goiter, ophthalmopathy, smoking, and FH provide evidence for
      interactions between genetic and environmental/endogenous factors; understanding
      these may allow preventive measures or better tailoring of therapies.

PMID- 16968789
TI  - Assessment of iodine status using dried blood spot thyroglobulin: development of
      reference material and establishment of an international reference range in
      iodine-sufficient children.
AB  - CONTEXT: Thyroglobulin (Tg) may be a valuable indicator of improving thyroid
      function in children after salt iodization. A recently developed Tg assay for use
      on dried whole blood spots (DBS) makes sampling practical, even in remote areas.
      OBJECTIVE: The study aim was to develop a reference standard for DBS-Tg,
      establish an international reference range for DBS-Tg in iodine-sufficient
      children, and test the standardized DBS-Tg assay in an intervention trial.
      DESIGN, PARTICIPANTS, AND INTERVENTIONS: Serum Tg reference material of the
      European Community Bureau of Reference (CRM-457) was adapted for DBS and its
      stability tested over 1 yr. DBS-Tg was determined in an international sample of 5
      to 14-yr-old children (n = 700) who were euthyroid, anti-Tg antibody negative,
      and residing in areas of long-term iodine sufficiency. In a 10-month trial in
      iodine-deficient children, DBS-Tg and other indicators of iodine status were
      measured before and after introduction of iodized salt. RESULTS: Stability of the
      CRM-457 Tg reference standard on DBS over 1 yr of storage at -20 and -50 C was
      acceptable. In the international sample of children, the third and 97th
      percentiles of DBS-Tg were 4 and 40 microg/liter, respectively. In the
      intervention, before introduction of iodized salt, median DBS-Tg was 49
      microg/liter, and more than two thirds of children had DBS-Tg values greater than
      40 microg/liter. After 5 and 10 months of iodized salt use, median DBS-Tg
      decreased to 13 and 8 microg/liter, respectively, and only 7 and 3% of children,
      respectively, had values greater than 40 microg/liter. DBS-Tg correlated well at
      baseline and 5 months with urinary iodine and thyroid volume. CONCLUSIONS: The
      availability of reference material and an international reference range
      facilitates the use of DBS-Tg for monitoring of iodine nutrition in school-age
      children.

PMID- 16968790
TI  - Low-grade systemic inflammation causes endothelial dysfunction in patients with
      Hashimoto's thyroiditis.
AB  - OBJECTIVE: The objective of this study was to assess whether low-grade systemic
      inflammation might contribute to the pathogenesis of endothelial dysfunction in
      patients with subclinical hypothyroidism (sHT) and autoimmune thyroiditis.
      BACKGROUND: sHT patients are characterized by peripheral endothelial dysfunction
      and low-grade inflammation. METHODS: In 53 sHT and 45 healthy subjects, we
      studied the forearm blood flow (strain-gauge plethysmography) response to
      intrabrachial acetylcholine (Ach) (0.15-15 microg/min.dl) with and without local
      vascular COX inhibition by intrabrachial indomethacin (50 microg/min.dl) or
      nitric oxide synthase blockade by N-mono methyl arginine (L-NMMA) (100
      microg/min.dl) or the antioxidant vitamin C (8 mg/min.dl). The protocol was
      repeated 2 h after systemic nonselective COX inhibition (100 mg indomethacin) or
      selective COX-2 blockade (200 mg celecoxib) oral administrations. RESULTS: sHT
      patients showed higher C-reactive protein and IL-6 values. In controls,
      vasodilation to Ach was blunted by L-NMMA and unchanged by vitamin C. In
      contrast, in sHT, the response to Ach, reduced in comparison with controls, was
      resistant to L-NMMA and normalized by vitamin C. In these patients, systemic but
      not local indomethacin normalized vasodilation to Ach and the inhibition of L
      NMMA on Ach. Similar results were obtained with celecoxib. When retested after
      indomethacin administration, vitamin C no longer succeeded in improving
      vasodilation to Ach in sHT patients. Response to sodium nitroprusside was
      unchanged by indomethacin or celecoxib. CONCLUSIONS: In sHT patients, low-grade
      chronic inflammation causes endothelial dysfunction and impaired nitric oxide
      availability by a COX-2-dependent pathway leading to increased production of
      oxidative stress.

PMID- 16968791
TI  - Acromegaly and somatotroph hyperplasia with adenomatous transformation due to
      pituitary metastasis of a growth hormone-releasing hormone-secreting pulmonary
      endocrine carcinoma.
AB  - CONTEXT: GHRH excess from extracranial endocrine tumors is known to cause
      somatotroph hyperplasia and acromegaly. Hypothalamic gangliocytomas producing
      GHRH are also known to be associated with pituitary adenomas causing acromegaly.
      OBJECTIVES: The objective of this study was to describe a case of acromegaly due
      to a pulmonary GHRH-secreting endocrine carcinoma with metastasis to the
      pituitary gland and to look at the peculiar histological features of this case.
      SUBJECT: The patient was a 44-yr-old woman who was diagnosed with a biopsy-proven
      metastatic pulmonary endocrine tumor during pregnancy. After delivery, she
      underwent radiation and chemotherapy for pulmonary and skeletal metastases. Her
      disease was clinically stable for 7 yr until she developed bitemporal hemianopia.
      She had symptoms and signs of acromegaly. METHODS: Imaging, biochemical, and
      histological studies were performed. RESULTS: Magnetic resonance imaging (MRI) of
      the brain confirmed the presence of a 2.6-cm lesion within the sella turcica
      extending above the sella and compressing the optic chiasm. Endocrine studies
      showed elevated serum levels of GH, prolactin, alpha-subunit of glycoprotein
      hormones, IGF-I, chromogranin A, and GHRH. The patient underwent uneventful
      transsphenoidal resection of the sellar tumor. Postoperatively, she noted an
      improvement in symptoms of acromegaly. Histological examination confirmed
      metastatic endocrine carcinoma to the pituitary, and immunohistochemistry
      localized GHRH to the tumor cells. The adjacent pituitary exhibited somatotroph
      hyperplasia with abundant reactivity for GH and alpha-subunit. In addition, there
      was focal neoplastic transformation to a sparsely granulated somatotroph
      phenotype with fibrous bodies. CONCLUSION: This is the first report of a GHRH
      producing endocrine tumor metastasizing to the pituitary and causing local
      hyperstimulation with somatotroph hyperplasia and adenomatous transformation.

PMID- 16968792
TI  - Positron emission tomography reveals correlations between brain metabolism and
      mood changes in hyperthyroidism.
AB  - CONTEXT: Hyperthyroidism is frequently associated with emotional distress. The
      underlying cerebral processes of the endocrine-induced mood changes are unclear.
      OBJECTIVE: The objective of this study was to investigate, for the first time,
      the neuronal correlates of thyrotoxicosis-associated psychic symptoms using
      positron emission tomography (PET). DESIGN: The study was designed as a cross
      sectional trial. SETTING: The study was performed at joint nuclear medicine and
      thyroid clinics. PATIENTS: Twelve patients with untreated Graves' hyperthyroidism
      were evaluated. METHODS: Levels of emotional distress were self-rated by means of
      the Hospital Anxiety and Depression Scale. Both patients and 20 age- and gender
      matched euthyroid controls underwent a brain fluorodeoxyglucose PET scan.
      Subsequently, the functional relationship between brain metabolism and the
      psychometric scores was analyzed. RESULTS: Compared with controls and visualized
      by fluorodeoxyglucose PET, hyperthyroid patients showed a decreased (P < 0.0001)
      glucose metabolism in the limbic system (uncus and inferior temporal gyrus).
      Activation foci in the posterior cingulate and in the inferior parietal lobe were
      correlated with both anxiety and depression scales (P < 0.001). Compared with
      patients with normal anxiety levels, those with increased anxiety yielded an
      enhanced glucose metabolism (P < 0.001) in the bilateral sensory association
      cortex. Serum free T3/free T4 levels negatively correlated with regional glucose
      metabolism in the medial posterior cingulate. CONCLUSIONS: Thyrotoxicosis and
      associated psychic symptoms are correlated to regional metabolic changes in the
      main structures of the limbic/paralimbic system.

PMID- 16968793
TI  - Nonclassic congenital lipoid adrenal hyperplasia: a new disorder of the
      steroidogenic acute regulatory protein with very late presentation and normal
      male genitalia.
AB  - CONTEXT: Lipoid congenital adrenal hyperplasia is a severe disorder of adrenal
      and gonadal steroidogenesis caused by mutations in the steroidogenic acute
      regulatory protein (StAR). Affected children typically present with life
      threatening adrenal insufficiency in early infancy due to a failure of
      glucocorticoid (cortisol) and mineralocorticoid (aldosterone) biosynthesis, and
      46,XY genetic males have complete lack of androgenization and appear
      phenotypically female due to impaired testicular androgen secretion in utero.
      OBJECTIVE: The objective of this study was to investigate whether nonclassic
      forms of this condition exist. PATIENTS AND METHODS: Sequence analysis of the
      gene encoding StAR was undertaken in three children from two families who
      presented with primary adrenal insufficiency at 2-4 yr of age; the males had
      normal genital development. Identified mutants were tested in a series of
      biochemical assays. RESULTS: DNA sequencing identified homozygous StAR mutations
      Val187Met and Arg188Cys in these two families. Functional studies of StAR
      activity in cells and in vitro and cholesterol-binding assays showed these
      mutants retained approximately 20% of wild-type activity. CONCLUSIONS: These
      patients define a new disorder, nonclassic lipoid congenital adrenal hyperplasia,
      and represent a new cause of nonautoimmune Addison disease (primary adrenal
      failure).

PMID- 16968794
TI  - Impaired caspase-3 expression by peripheral T cells in chronic autoimmune
      thyroiditis and in autoimmune polyendocrine syndrome-2.
AB  - CONTEXT: Activation-induced cell death (AICD) is a major mechanism in the
      regulation of peripheral tolerance, and caspase-3 represents its major
      executioner. AICD impairment contributes to the persistence of autoreactive T
      cells, and defective AICD has been reported in autoimmune thyroiditis as well as
      in type 1 diabetes mellitus. OBJECTIVE: The objective of this study was to
      evaluate the involvement of caspase-3 in the regulation of AICD resistance in
      thyroid and polyendocrine autoimmunity. DESIGN/SETTINGS/PATIENTS/INTERVENTION:
      Caspase-3 expression was analyzed in peripheral blood lymphocytes from 26 adults
      (A-AT) and 25 children (Y-AT) affected by autoimmune thyroiditis and 13
      individuals affected by chronic autoimmune thyroiditis plus Addison's disease
      [autoimmune polyendocrine syndrome-2 (APS-2)] in comparison with 32 age-matched
      normal control subjects (NC). OUTCOME MEASURES: Caspase-3 mRNA expression in
      peripheral T cells was evaluated by quantitative real-time PCR; protein
      expression of both procaspase-3 and activated caspase-3 by Western blot analysis
      was followed by scanning densitometry. RESULTS: Caspase-3 mRNA expression was
      significantly reduced in resting lymphocytes from both A-AT (P = 0.001) and Y-AT
      (P = 0.016) compared with NC. After lymphocyte activation, protein levels of
      caspase-3 active form were significantly reduced in A-AT (P = 0.023) and Y-AT (P
      = 0.001) compared with NC. The APS-2 group displayed characteristics similar to
      the A-AT group because both caspase-3 mRNA and protein active form levels were
      significantly reduced compared with NC (P = 0.004 and 0.002, respectively).
      CONCLUSION: Our data show that peripheral lymphocytes of subjects affected by
      thyroid autoimmunity or APS-2 show defective expression of the major executioner
      of AICD, thus potentially contributing to AICD resistance and to the development
      of autoimmunity.

PMID- 16968795
TI  - High prevalence of pituitary adenomas: a cross-sectional study in the province of
      Liege, Belgium.
AB  - CONTEXT: Prevalence data are important for assessing the burden of disease on the
      health care system; data on pituitary adenoma prevalence are very scarce.
      OBJECTIVE: The objective of the study was to measure the prevalence of clinically
      relevant pituitary adenomas in a well-defined population. DESIGN: This was a
      cross-sectional, intensive, case-finding study performed in three regions of the
      province of Liege, Belgium, to measure pituitary adenoma prevalence as of
      September 30, 2005. SETTING: The study was conducted in specialist and general
      medical practitioner patient populations, referral hospitals, and investigational
      centers. METHODS: Three demographically and geographically distinct districts of
      the province of Liege were delineated precisely using postal codes. Medical
      practitioners in these districts were recruited, and patients with pituitary
      adenomas under their care were identified. Diagnoses were confirmed after
      retrieval of clinical, hormonal, radiological, and pathological data; full
      demographic and therapeutic follow-up data were collected in all cases. RESULTS:
      Sixty-eight patients with clinically relevant pituitary adenomas were identified
      in a population of 71,972 individuals; the mean (+/- sd) prevalence was 94 +/-
      19.3 cases per 100,000 population (95% confidence interval, 72.2 to 115.8). The
      group was 67.6% female and had a mean age at diagnosis of 40.3 yr; 42.6% had
      macroadenomas and 55.9% underwent surgery. Prolactinomas comprised 66% of the
      group, with the rest having nonsecreting tumors (14.7%), somatotropinomas
      (13.2%), or Cushing's disease (5.9%); 20.6% had hypopituitarism. CONCLUSION: The
      prevalence of pituitary adenomas in the study population (one case in 1064
      individuals) was more than 3.5-5 times that previously reported. This increased
      prevalence may have important implications when prioritizing funding for research
      and treatment of pituitary adenomas.

PMID- 16968796
TI  - Serum resistin and hepatic fat content in nondiabetic individuals.
AB  - CONTEXT: Serum resistin concentration is increased in patients with nonalcoholic
      fatty liver disease in proportion with the histological severity of the disease,
      but the relevance of the contribution of fatty liver per se is undetermined.
      OBJECTIVE: The objective of the study was to assess the relationship between
      serum resistin and the degree of ectopic fat accumulation in vivo in humans.
      DESIGN AND SETTING: The hepatic fat (IHF) content, measured quantitatively by
      means of 1H magnetic resonance spectroscopy, serum resistin, and biochemical and
      hormonal metabolic correlates of fatty liver and insulin resistance were assessed
      in 28 affected patients, and 47 individuals with comparable anthropometric
      features served as controls. Insulin sensitivity was estimated using the computer
      homeostatic model assessment (HOMA)-2. A subset of volunteers (n = 18) also
      underwent 1H magnetic resonance spectroscopy of the calf muscles to assess the
      intramyocellular lipid content (IMCL). RESULTS: In patients with fatty liver, the
      IHF content (13 +/- 8 vs. 2 +/- 1% wet weight; P < 0.0001) and also the soleus
      IMCL content (P < 0.05) were increased in comparison with the controls. Patients
      with fatty liver had lower insulin sensitivity (HOMA2 insulin sensitivity: 59 +/-
      24 vs. 72 +/- 29%; P < 0.04), serum resistin (3.4 +/- 0.8 vs. 3.9 +/- 1.0 ng/ml;
      P < 0.02), and adiponectin (P < 0.01) concentrations. Serum resistin was
      inversely correlated with the IHF content (r = -0.35; P < 0.003) and the soleus
      IMCL content (r = -0.51; P < 0.05) but not HOMA2 insulin sensitivity. CONCLUSION:
      This study demonstrates that excessive ectopic fat accumulation in the liver and
      skeletal muscle of insulin-resistant subjects is associated with lower serum
      resistin concentration and not with hyperresistinemia.

PMID- 16968797
TI  - Differences in follicle-stimulating hormone secretion between 45,X monosomy
      Turner syndrome and 45,X/46,XX mosaicism are evident at an early age.
AB  - CONTEXT: Little information exists regarding FSH values in very young girls with
      Turner syndrome (TS). OBJECTIVES: The objective of the study was to evaluate the
      pattern, natural progression, and karyotype-related differences in FSH secretion
      in young, prepubertal girls with TS. STUDY DESIGN: FSH was measured at study
      entry and annually for 2 yr. SETTING: The Toddler Turner study was conducted at
      11 U.S. pediatric endocrine centers. STUDY PARTICIPANTS: Eighty-eight girls with
      karyotype-proven TS aged 9 months to 4 yr participated in the study. MAIN OUTCOME
      MEASURES: By-karyotype differences in FSH concentration and age-related changes
      in FSH were measured. RESULTS: Mean (+/- SD) FSH was markedly elevated in the
      45,X (n = 56: 68.3 +/- 36.0 IU/liter) and Other groups [n = 15 (excluding three
      subjects with Y-containing karyotypes): 52.7 +/- 50.8 IU/liter] but was minimally
      elevated in girls with 45,X/46,XX mosaicism (n = 14: 10.1 +/- 13.5 IU/liter, P <
      0.005 both comparisons). Over the 2-yr period, FSH declined in the 45,X group (
      13.4 IU/liter.yr, P < 0.0001). Nonetheless, only three of 159 FSH values fell
      within normal range for age at any time during the 2-yr study. FSH decline was
      similar in the Other group (-14.3 IU/liter.yr, P = 0.0032). In contrast, no
      significant decrease in FSH with age was observed in the 45,X/46,XX group.
      CONCLUSIONS: In contrast to the original report of FSH concentrations in
      individuals with TS, this study demonstrates distinct differences in patterns of
      FSH secretion between young girls with monosomy TS, who have persistent elevation
      of FSH to age 6 yr, and those with 45,X/46,XX mosaicism, whose FSH values suggest
      retained ovarian function in the majority. These findings have implications for
      patient management and family counseling.

PMID- 16968798
TI  - The relation of thyroid function and ventricular repolarization: decreased serum
      thyrotropin levels are associated with short rate-adjusted QT intervals.
AB  - CONTEXT: The linkage of thyroid dysfunction with ventricular repolarization
      properties has not been investigated extensively, although alterations might be
      associated with an increased ventricular vulnerability. OBJECTIVE: The objective
      of the study was to investigate whether there is an association between
      functional thyroid status and rate-adjusted QT intervals (QTc). DESIGN, SETTING,
      AND PARTICIPANTS: The population-based Study of Health in Pomerania included 4310
      subjects aged 20-79 yr. Data of 3610 subjects (1862 women and 1748 men) without
      branch bundle blocks or pacemaker were available for the present analyzes. MAIN
      OUTCOME MEASURES: QTc with respect to thyroid status. Short QTc was defined below
      the 25th percentile, and long QTc above the 75th percentile of the gender
      specific distribution. RESULTS: TSH levels were positively associated with QTc
      independent from potential confounders in multivariable analyses (P for trend =
      0.001). Subjects with decreased TSH levels had shorter QTc than those with normal
      TSH levels (426.4 +/- 8.2 vs. 430.2 +/- 8.2; P < 0.001). Adjusted odds ratios for
      short QTc in subjects with elevated, normal, and decreased TSH were 0.87 (95%
      confidence interval 0.58-1.31), 1.00 (reference), and 1.53 (95% confidence
      interval 1.16-2.03), respectively (P for trend = 0.008). CONCLUSION: TSH levels
      were positively related to QTc in a population-based sample. Subjects with
      decreased serum TSH levels had an increased risk for short QTc. Whether these
      findings are of clinical significance has to be investigated by further studies.

PMID- 16968799
TI  - A homozygous R262Q mutation in the gonadotropin-releasing hormone receptor
      presenting as constitutional delay of growth and puberty with subsequent
      borderline oligospermia.
AB  - CONTEXT: The GnRH receptor plays a central role in regulating gonadotropin
      synthesis and release, and several mutations in the GNRHR gene have been reported
      in patients with idiopathic or familial forms of isolated hypogonadotropic
      hypogonadism (IHH). OBJECTIVE: The objective of the study was to investigate
      whether partial loss-of-function mutations in the GnRH receptor might be
      responsible for delayed puberty phenotypes. PATIENTS: Patients included sibling
      pairs with delayed puberty (n = 8) or those in whom one brother had delayed
      puberty and another had hypogonadotropic hypogonadism (n = 3). METHODS: Methods
      included mutational analysis of the GNRHR gene. RESULTS: A homozygous R262Q
      mutation in the GnRH receptor was identified in two brothers from one family. In
      this kindred, the proband presented at 15 yr of age with delayed puberty. After a
      short course of testosterone, he seemed to be progressing through puberty
      appropriately and was discharged from follow-up. His younger brother was also
      referred with delayed puberty but showed little progress after treatment.
      Frequent sampling revealed detectable but apulsatile LH and FSH release. His
      clinical progress was consistent with IHH, and he requires ongoing testosterone
      replacement. CONCLUSIONS: Homozygous partial loss-of-function mutations in the
      GnRH receptor, such as R262Q, can present with variable phenotypes including
      apparent delayed puberty. Ongoing clinical vigilance might be required when
      patients are discharged from follow-up, especially when there is a family history
      of delayed puberty or IHH because oligospermia and reduced bone mineralization
      can occur with time.

PMID- 16968800
TI  - Review: The role of insulin resistance in nonalcoholic fatty liver disease.
AB  - CONTEXT: Insulin resistance is an almost universal finding in nonalcoholic fatty
      liver disease (NAFLD). This review outlines the evidence linking insulin
      resistance and NAFLD, explores whether liver fat is a cause or consequence of
      insulin resistance, and reviews the current evidence for treatment of NAFLD.
      EVIDENCE ACQUISITION: Evidence from epidemiological, experimental, and clinical
      research studies investigating NAFLD and insulin resistance was reviewed.
      EVIDENCE SYNTHESIS: Insulin resistance in NAFLD is characterized by reductions in
      whole-body, hepatic, and adipose tissue insulin sensitivity. The mechanisms
      underlying the accumulation of fat in the liver may include excess dietary fat,
      increased delivery of free fatty acids to the liver, inadequate fatty acid
      oxidation, and increased de novo lipogenesis. Insulin resistance may enhance
      hepatic fat accumulation by increasing free fatty acid delivery and by the effect
      of hyperinsulinemia to stimulate anabolic processes. The impact of weight loss,
      metformin, and thiazolidinediones, all treatments aimed at improving insulin
      sensitivity, as well as other agents such as vitamin E, have been evaluated in
      patients with NAFLD and have shown some benefit. However, most intervention
      studies have been small and uncontrolled. CONCLUSION: Insulin resistance is a
      major feature of NAFLD that, in some patients, can progress to steatohepatitis.
      Treatments aimed at reducing insulin resistance have had some success, but larger
      placebo-controlled studies are needed to fully establish the efficacy of these
      interventions and possibly others in reducing the deleterious effects of fat
      accumulation in the liver.

PMID- 16968801
TI  - ENPP1 variants and haplotypes predispose to early onset obesity and impaired
      glucose and insulin metabolism in German obese children.
AB  - CONTEXT: ENPP1 (nucleotide pyrophosphatase/phosphodiesterase-1) encodes a
      membrane-bound glycoprotein that inhibits the insulin-receptor tyrosine kinase
      activity, resulting in reduced insulin sensitivity. Hence, variants in this gene
      may be related to obesity and insulin resistance. OBJECTIVE: Therefore, in this
      study, we aimed to explore the role of ENPP1 genetic variants in obesity and
      related traits in a representative population of Caucasian children and in
      cohorts of obese children with detailed metabolic characteristics including oral
      glucose tolerance test. DESIGN: We genotyped the K121Q, IVS20delT-11, and
      A/G+1044TGA ENPP1 genetic variants for association analyses in 712 schoolchildren
      (346 boys and 366 girls; mean age 12 +/- 3 yr; mean body mass index-sd score 0.09
      +/- 0.04) and in independent cohorts of 205 obese children from Leipzig and 195
      obese children from Datteln, Germany. RESULTS: We identified a significantly
      increased risk of obesity in Leipzig children carrying the 121Q variant (adjusted
      odds ratio, 1.82; 95% confidence interval, 1.30-2.56; P = 0.0005) or the [Q-delT
      G] haplotype [1.75 (1.17-2.62), P = 0.006] as compared with a lean control group.
      This was replicated in another independent obesity/overweight cohort from Leipzig
      as well as obese children from Datteln. In addition, obese children from Leipzig
      with the [Q-delT-G] haplotype were characterized by impaired glucose metabolism,
      whereas the [K-delT-G] and [K-insT-A] haplotypes were significantly associated
      with improved insulin sensitivity and glucose metabolism (all P < 0.05 after
      adjusting for age, gender, and body mass index). CONCLUSIONS: In conclusion, our
      study suggests a potential role of the K121Q polymorphism or derived ENPP1
      haplotypes in increased susceptibility to obesity and early impairment of glucose
      and insulin metabolism in children.

PMID- 16968802
TI  - Salivary alpha-amylase levels after yohimbine challenge in healthy men.
AB  - CONTEXT: We and others have previously shown that standardized psychosocial
      stress significantly increases salivary alpha-amylase (sAA), but it remains
      unclear whether sAA reflects autonomic nervous system activation. OBJECTIVE: The
      aim of this study was to assess cardiovascular effects and sAA and catecholamine
      secretion after iv injection of yohimbine. DESIGN AND SETTING: We conducted a
      randomized double-blind placebo-controlled study at an academic research unit.
      PARTICIPANTS: Thirteen healthy males (aged 20-28 yr) were examined. INTERVENTION:
      Participants received iv injection of yohimbine (0.4 microg/kg) or placebo (0.9%
      NaCl). MAIN OUTCOME MEASURES: Eight saliva and blood samples were taken before
      and after injection for the assessment of salivary flow rate and sAA and
      catecholamine concentrations. In addition, blood pressure, mood, and anxiety were
      assessed repeatedly. RESULTS: Yohimbine induced increases of sAA activity and
      output in comparison to placebo (P = 0.034). Blood pressure (P < 0.001), salivary
      flow rate (P = 0.007), and catecholamines (P < 0.001) were also significantly
      increased. No significant correlations between alpha-amylase parameters and
      catecholamines were observed. CONCLUSIONS: The results indicate that yohimbine
      administration activates not only autonomic parameters but also sAA via
      adrenergic mechanisms, suggesting that sAA might be an indirect indicator of the
      central sympathetic system.

PMID- 16968803
TI  - Hook needle-guided excision of recurrent differentiated thyroid cancer in
      previously operated neck compartments: a safe technique for small, nonpalpable
      recurrent disease.
AB  - CONTEXT: As a result of more sensitive techniques to detect recurrent thyroid
      cancer, the number of patients presenting with small, nonpalpable recurrent
      thyroid cancer in cervical lymph nodes is increasing. Surgical excision of
      nonpalpable recurrent thyroid cancer can be difficult, particularly in a
      previously operated area. OBJECTIVE: The objective of this study was to
      investigate whether preoperative insertion of a hook needle under ultrasound
      guidance is useful in neck reoperations for recurrent thyroid cancer. PATIENTS:
      Ten consecutive patients presenting over a 4-month period with nonpalpable,
      ultrasound-visible, fine needle biopsy-proven recurrent thyroid cancer in
      previously operated neck compartment(s) were studied. MAIN OUTCOME MEASURES: We
      measured whether it was technically possible to insert a hook needle
      preoperatively, rate of negative neck exploration, and complication rate.
      RESULTS: The hook needle was inserted in seven patients. In three patients, the
      hook needle was not inserted; one patient had palpable disease 4 months after the
      preoperative clinic visit, one patient had a tumor too close to the carotid
      artery, and one patient had multiple bilateral foci of recurrent disease in the
      central neck. One patient had bleeding after insertion of the needle due to a
      penetration of an anterior jugular vein that was easily managed at neck
      reexploration. No other complication occurred during the hook needle insertion,
      and the only surgical complication was a transient recurrent nerve palsy. All
      pathology reports showed malignant disease. CONCLUSION: Hook needle-guided
      excision of recurrent thyroid cancer is feasible and appears to be a promising
      tool for safe and successful reoperation of patients with small recurrent thyroid
      cancer in cervical lymph nodes.

PMID- 16968804
TI  - Dynamic strength training improves insulin sensitivity without altering plasma
      levels and gene expression of adipokines in subcutaneous adipose tissue in obese
      men.
AB  - CONTEXT: Obesity is characterized by a low-grade inflammatory state, which could
      play a role in insulin resistance. Dynamic strength training improves insulin
      sensitivity. OBJECTIVE: The objective of this study was to investigate, in obese
      subjects, whether the insulin sensitizing effect of dynamic strength training is
      associated with changes in plasma levels and gene expression of adipokines
      potentially involved in the development of insulin resistance. DESIGN: Twelve
      obese male subjects were investigated before and at the end of 3 months of
      dynamic strength training. Insulin sensitivity was evaluated using euglycemic
      hyperinsulinemic clamp. Blood samples and needle biopsy samples of sc abdominal
      adipose tissue were obtained. The plasma levels and adipose tissue mRNA levels of
      adiponectin, leptin, IL-1beta, IL-6, and TNF-alpha were determined. RESULTS: The
      training induced an increase in the whole-body glucose disposal rate by 24% (P =
      0.04). The body weight was not altered during the training. Plasma levels of
      leptin decreased during the training (16.6 +/- 6.3 vs. 13.1 +/- 5.7 ng/ml) by 21%
      (P < 0.02), whereas no change in plasma levels of other adipokines and C-reactive
      protein was observed. Gene expression of the investigated adipokines was not
      changed in sc adipose tissue during the training. CONCLUSIONS: In obese subjects,
      the dynamic strength training resulted in an improvement of whole-body insulin
      sensitivity. The increase in insulin sensitivity was not associated with training
      induced modifications of plasma levels or adipose tissue gene expression of
      adipokines supposedly involved in the development of insulin resistance.

PMID- 16968806
TI  - Premature mortality in patients with Addison's disease: a population-based study.
AB  - BACKGROUND: The survival rate of patients with primary adrenal insufficiency
      (Addison's disease) undergoing currently accepted replacement therapy is not
      known, although well-informed patients are considered to have a normal survival
      rate. In this study, we evaluated the mortality of patients with Addison's
      disease in Sweden. METHODS: A population-based, retrospective, observational
      study was performed, using the National Swedish Hospital and Cause of Death
      Registers, covering the period from 1987-2001. After a diagnosis of Addison's
      disease, each patient was followed until the end of follow-up or death. Mortality
      was compared with that of the Swedish background population. FINDINGS: We
      identified 1675 patients (995 women and 680 men) diagnosed with primary adrenal
      insufficiency. The average follow-up from initial diagnosis was 6.5 yr. Five
      hundred seven patients died during the study period compared with an expected
      199. The risk ratio for all-cause mortality was 2.19 (confidence interval 1.91
      2.51) for men and 2.86 (confidence interval 2.54-3.20) for women. The excess
      mortality in both men and women was attributed to cardiovascular, malignant, and
      infectious diseases. Concomitant diabetes mellitus was observed in 12% of the
      patients, but only contributed to the increased mortality to a minor extent.
      INTERPRETATION: Compared with the background population, we observed that the
      risk ratio for death was more than 2-fold higher in patients with Addison's
      disease. Cardiovascular, malignant, and infectious diseases were responsible for
      the higher mortality rate.

PMID- 16968807
TI  - Identification and functional analysis of the novel S179R POU1F1 mutation
      associated with combined pituitary hormone deficiency.
AB  - CONTEXT: The pituitary-specific transcription factor 1 plays a key role in the
      development and differentiation of three pituitary cell types: somatotrophs,
      lactotrophs, and thyrotrophs. Several mutations of the human gene (called POU1F1)
      have been shown to be responsible for a phenotype of combined pituitary hormone
      deficiency involving GH, prolactin (PRL), and TSH. OBJECTIVE: We have identified
      a novel homozygous C to G mutation in exon 4 of the POU1F1 gene (S179R) in a
      patient with this rare phenotype. We analyzed the functional consequences of this
      S179R mutation associated with a single-amino acid change in the POU-specific
      domain. METHODS: Consequences of this mutation on transcriptional activities by
      transfection studies in alphaT3 cells, DNA binding ability by EMSA, structural
      properties, and nuclear accumulation of POU1F1 were investigated. RESULTS: The
      transactivation capacity of this mutant was markedly decreased on the GH1, PRL,
      TSHbeta, and POU1F1 genes. Interestingly, this mutation abolished the functional
      interaction of POU1F1 on the PRL promoter with the coactivator cAMP response
      element-binding protein-binding protein but not with the transcription factor LIM
      homeodomain transcription factor 3. The S179R mutant displayed normal nuclear
      accumulation but a markedly decreased binding to a DNA response element in
      keeping with crystallographic data, suggesting that the S179R mutation might
      interfere with DNA binding. CONCLUSIONS: Together with previous data, our study
      indicates that both DNA binding and interaction with cofactors like cAMP response
      element-binding protein-binding protein are critical for POU1F1 function and that
      functional and structural properties of abnormal POU1F1 proteins are variously
      influenced by the type of mutations.

PMID- 16968805
TI  - Direct demonstration of an antiinflammatory effect of simvastatin in subjects
      with the metabolic syndrome.
AB  - CONTEXT: Metabolic syndrome (MS) is characterized by low-grade inflammation and
      confers an increased risk for cardiovascular disease. Hydroxymethylglutaryl
      coenzyme A reductase inhibitors (statins) reduce cardiovascular events in MS
      patients. There is a paucity of data examining the effect of statins on
      inflammation in MS. OBJECTIVE: We aimed to test the effect of simvastatin (40
      mg/d) compared with placebo on biomarkers of inflammation [high-sensitivity C
      reactive protein (hsCRP) and monocytic cytokines TNF, IL-6, and IL-1] in MS
      subjects. DESIGN AND PATIENTS: We conducted a randomized, double-blind, placebo
      controlled study at the University of California, Davis, Medical Center.
      PARTICIPANTS: Participants were subjects with MS. INTERVENTION: Simvastatin (40
      mg/d) or placebo was administered for 8 wk. METHODS AND RESULTS: The hsCRP levels
      were assayed using a high-sensitivity immunoassay. Monocyte cytokines were
      assayed by ELISA after activation with lipopolysaccharide. Simvastatin therapy
      significantly decreased hsCRP levels in MS subjects compared with placebo (P <
      0.0005) and resulted in a significant reduction in plasma and lipopolysaccharide
      activated monocytic release of IL-6 and TNF (P < 0.025). Simvastatin therapy
      significantly decreased nuclear factor-kappaB and increased Akt activity in MS
      subjects compared with placebo. To gain mechanistic insights, human monocytes
      were pretreated with lovastatin with and without mevalonate or a phosphatidyl-3
      kinase inhibitor or Rho kinase inhibitor. Lovastatin significantly decreased Rho
      kinase and nuclear factor-kappaB activity, significantly increased Akt activity,
      and resulted in decreased monocyte IL-6 levels; these effects were reversed with
      mevalonate and geranylgeranyl pyrophosphate, indicating direct effects of statins
      on protein prenylation. CONCLUSIONS: Thus, we show a direct antiinflammatory
      effect of simvastatin therapy in MS. These findings could partly explain the
      benefit of statin therapy in these patients.

PMID- 16968808
TI  - Epistemological issues in omics and high-dimensional biology: give the people
      what they want.
AB  - Gene expression microarrays have been the vanguard of new analytic approaches in
      high-dimensional biology. Draft sequences of several genomes coupled with new
      technologies allow study of the influences and responses of entire genomes rather
      than isolated genes. This has opened a new realm of highly dimensional biology
      where questions involve multiplicity at unprecedented scales: thousands of
      genetic polymorphisms, gene expression levels, protein measurements, genetic
      sequences, or any combination of these and their interactions. Such situations
      demand creative approaches to the processes of inference, estimation, prediction,
      classification, and study design. Although bench scientists intuitively grasp the
      need for flexibility in the inferential process, the elaboration of formal
      supporting statistical frameworks is just at the very start. Here, we will
      discuss some of the unique statistical challenges facing investigators studying
      high-dimensional biology, describe some approaches being developed by statistical
      scientists, and offer an epistemological framework for the validation of
      proffered statistical procedures. A key theme will be the challenge in providing
      methods that a statistician judges to be sound and a biologist finds informative.
      The shift from family-wise error rate control to false discovery rate estimation
      and to assessment of ranking and other forms of stability will be portrayed as
      illustrative of approaches to this challenge.

PMID- 16968809
TI  - Pharmacology and signaling properties of epidermal growth factor receptor
      isoforms studied by bioluminescence resonance energy transfer.
AB  - We have developed a new assay for measuring epidermal growth factor receptor
      (EGFR) activation using the bioluminescence resonance energy transfer (BRET)
      technology, which directly measures the recruitment of signaling proteins to
      activated EGFR. Our results demonstrate that EGFR BRET assays precisely measure
      the pharmacology and signaling properties of EGFR expressed in human embryonic
      kidney 293T cells. EGFR BRET assays are highly sensitive to known EGFR ligands
      [pEC50 of epidermal growth factor (EGF)=10.1+/-0.09], consistent with previous
      pharmacological methods for measuring EGFR activation. We applied EGFR BRET
      assays to study the characteristics of somatic EGFR mutations that were recently
      identified in lung cancer. In agreement with recent reports, we detected
      constitutively active mutant EGFR isoforms, which predominantly signal through
      the phosphatidylinositol-3-kinase/Akt pathway. The EGFR inhibitors Iressa or
      Tarceva are severalfold more potent in inhibiting constitutive activity of mutant
      EGFR isoforms compared with wild-type EGFR. Notable, our results reveal that most
      of the mutant EGFR isoforms tested were significantly impaired in their response
      to EGF. The highest level of constitutive activity and nearly complete loss of
      epidermal growth factor responsiveness was detected in isoforms that carry the
      activating mutation L858R and the secondary resistance mutation T790M. In
      summary, our study reveals that somatic mutations in EGFR quantitatively differ
      in pharmacology and signaling properties, which suggest the possibility of
      differential clinical responsiveness to treatment with EGFR inhibitors.
      Furthermore, we demonstrate that the EGFR BRET assays are a useful tool to study
      the pharmacology of ligand-induced interaction between EGFR and signaling pathway
      specifying adapter proteins.

PMID- 16968810
TI  - Rapid and robust protection against cocaine-induced lethality in rats by the
      bacterial cocaine esterase.
AB  - There is no approved means to prevent the toxic actions of cocaine. Cocaine
      esterase (CocE) is found in a rhodococcal strain of bacteria that grows in the
      rhizosphere soil around the coca plant and has been found to hydrolyze cocaine in
      vitro. The esteratic activity of CocE (0.1-1.0 mg, i.v.) was characterized and
      confirmed in vivo by assessing its ability to prevent cocaine-induced convulsions
      and lethality in the rat. The therapeutic efficiency of the enzyme was
      demonstrated by the increasing dose of cocaine (100-1000 mg/kg, i.p.) required to
      produce toxic effects after a single intravenous injection of CocE. The enzyme
      demonstrated rapid kinetics for cocaine degradation in rat and human serum. Two
      catalytically inactive mutants of CocE (S117A or Y44F) failed to protect rats
      from the toxic effects of cocaine, confirming the protective effects are due to
      hydrolytic activity. However, butyrylcholinesterase, an endogenous cocaine
      hydrolyzing enzyme, was inactive (1.3-13 mg, i.v.) in this rat toxicity
      procedure. Furthermore, CocE did not block the lethality of WIN-35065-2 (560
      mg/kg, i.p.), a cocaine analog that lacks the benzoyl ester moiety targeted by
      CocE. This characterization of CocE provides preliminary evidence that the enzyme
      could serve as a suitable antidote to cocaine toxicity in humans.

PMID- 16968811
TI  - Association of hormonal dysregulation with metabolic syndrome in older women:
      data from the InCHIANTI study.
AB  - Metabolic syndrome (MetS) is a strong risk factor for type 2 diabetes and
      cardiovascular disease. Conditions associated with hyperandrogenism are often
      associated with glucose intolerance and other features of MetS in young women. As
      the prevalence of MetS increases with age and is probably multifactorial, it is
      reasonable to hypothesize that age-related changes in androgens and other
      hormones might contribute to the development of MetS in older persons. However,
      this hypothesis has never been tested in older women. We hypothesized that high
      levels of testosterone, dehydroepiandrosterone sulfate (DHEA-S), and cortisol and
      low levels of sex hormone-binding globulin (SHBG) and IGF-I would be associated
      with MetS in a representative cohort of older Italian women independently of
      confounders (including inflammatory markers). After exclusion of participants on
      hormone replacement therapy and those with a history of bilateral oophorectomy,
      512 women (>/=65 yr) had complete data on testosterone, cortisol, DHEA-S, SHBG,
      fasting insulin, total and free IGF-I, IL-6, and C-reactive protein (CRP). MetS
      was defined according to ATP-III criteria. Insulin resistance was calculated
      according to HOMA. MetS was found in 145 women (28.3%). Participants with vs.
      those without MetS had higher age-adjusted levels of bioavailable testosterone (P
      < 0.001), IL-6 (P < 0.001), CRP (P < 0.001), and HOMA (P < 0.001) and lower
      levels of SHBG (P < 0.001). After adjustment for potential confounders,
      participants with decreased SHBG had an increased risk of MetS (P < 0.0001) vs.
      those with low SHBG. In a further model including all hormones and confounders,
      log SHBG was the only independent factor associated with MetS (OR: 0.44, 95% CI
      0.21-0.91, P = 0.027). In older women, SHBG is negatively associated with MetS
      independently of confounders, including inflammatory markers and insulin
      resistance. Further studies are needed to support the notion that raising SHBG is
      a potential therapeutic target for prevention and treatment of MetS.

PMID- 16968812
TI  - Carotid artery intima-media thickness is associated with insulin-mediated glucose
      disposal in nondiabetic normotensive offspring of type 2 diabetic patients.
AB  - The aim of this study was to investigate whether insulin resistance is
      independently associated with early manifestations of atherosclerosis. To this
      end, 176 normotensive offspring of type 2 diabetic patients were subjected to
      euglycemic hyperinsulinemic clamp to assess insulin sensitivity. Early
      atherosclerosis was studied by ultrasonography of the common carotid artery. Of
      the total 176 subjects, 145 were glucose tolerant, 18 had impaired fasting
      glucose, and 13 had impaired glucose tolerance. Univariate correlations showed
      that age, body mass index, waist, blood pressure, 2-h postchallenge glucose,
      fasting insulin, triglycerides, interleukin-6, fibrinogen, and white blood cell
      count were significantly correlated with carotid intima-media thickness (IMT),
      whereas HDL cholesterol and glucose disposal showed a negative correlation. A
      stepwise multivariate regression analysis including sex, age, waist
      circumference, smoking status, systolic blood pressure, diastolic blood pressure,
      triglyceride, HDL cholesterol, 2-h postchallenge glucose, plasma IL-6,
      fibrinogen, white blood cell count, insulin-stimulated glucose disposal, and
      fasting insulin showed that the four variables that remained significantly
      associated with carotid IMT were waist circumference, insulin-stimulated glucose
      disposal, white blood cell count, and diastolic blood pressure, accounting for
      33.7% of its variation. These findings support the concept that insulin
      sensitivity, rather than plasma insulin levels, is associated with early
      atherosclerosis in nondiabetic normotensive offspring of type 2 diabetic
      patients.

PMID- 16968813
TI  - Effects of pioglitazone and metformin on beta-cell function in nondiabetic
      subjects at high risk for type 2 diabetes.
AB  - Thiazolidinediones (TZDs) and metformin decreased the incidence of diabetes in
      subjects at risk for developing diabetes and improved peripheral or hepatic
      insulin sensitivity, respectively. Whether they also directly improved beta-cell
      function is not clear. In vitro studies showed improved beta-cell function in
      response to TZDs and metformin; however, the effects of TZDs or metformin on beta
      cell function in humans are still uncertain. We hypothesized that both TZDs and
      metformin directly affect beta-cell function. We evaluated beta-cell function and
      insulin sensitivity (S(I)) in subjects with impaired glucose tolerance or a
      history of gestational diabetes using oral and intravenous glucose tolerance
      tests in addition to the glucose-potentiated arginine stimulation test. In
      contrast to metformin, pioglitazone improved S(I), glucose tolerance, and insulin
      independent glucose disposal [glucose effectiveness (S(G))]. Neither pioglitazone
      nor metformin significantly improved beta-cell compensation for insulin
      resistance [disposition index (DI)], but the change in DI significantly
      correlated with baseline S(I). Insulin secretion in response to arginine at
      maximally potentiating glucose levels (AIR(max)) tended to increase after
      metformin and to decrease after pioglitazone; however, when adjusted for S(I),
      the changes were not significant. Our results demonstrate that, in nondiabetic
      subjects at risk for diabetes, pioglitazone, but not metformin, significantly
      improved glucose tolerance by improving S(I) and S(G). We did not find any
      evidence that either pioglitazone or metformin improved beta-cell function.
      Improved beta-cell compensation was observed primarily in the subgroup of
      subjects that had the lowest S(I) at baseline.

PMID- 16968814
TI  - The journey of developing hematopoietic stem cells.
AB  - Hematopoietic stem cells (HSCs) develop during embryogenesis in a complex process
      that involves multiple anatomical sites. Once HSC precursors have been specified
      from mesoderm, they have to mature into functional HSCs and undergo self-renewing
      divisions to generate a pool of HSCs. During this process, developing HSCs
      migrate through various embryonic niches, which provide signals for their
      establishment and the conservation of their self-renewal ability. These processes
      have to be recapitulated to generate HSCs from embryonic stem cells. Elucidating
      the interactions between developing HSCs and their niches should facilitate the
      generation and expansion of HSCs in vitro to exploit their clinical potential.

PMID- 16968815
TI  - Arteries define the position of the thyroid gland during its developmental
      relocalisation.
AB  - During vertebrate development, the thyroid gland undergoes a unique
      relocalisation from its site of induction to a distant species-specific position
      in the cervical mesenchyme. We have analysed thyroid morphogenesis in wild-type
      and mutant zebrafish and mice, and find that localisation of growing thyroid
      tissue along the anteroposterior axis in zebrafish is linked to the development
      of the ventral aorta. In grafting experiments, ectopic vascular cells influence
      the localisation of thyroid tissue cell non-autonomously, showing that vessels
      provide guidance cues in zebrafish thyroid morphogenesis. In mouse thyroid
      development, the midline primordium bifurcates and two lobes relocalise cranially
      along the bilateral pair of carotid arteries. In hedgehog-deficient mice, thyroid
      tissue always develops along the ectopically and asymmetrically positioned
      carotid arteries, suggesting that, in mice (as in zebrafish), co-developing major
      arteries define the position of the thyroid. The similarity between zebrafish and
      mouse mutant phenotypes further indicates that thyroid relocalisation involves
      two morphogenetic phases, and that variation in the second phase accounts for
      species-specific differences in thyroid morphology. Moreover, the involvement of
      vessels in thyroid relocalisation sheds new light on the interpretation of
      congenital thyroid defects in humans.

PMID- 16968816
TI  - Ephrin A/EphA controls the rostral turning polarity of a lateral commissural
      tract in chick hindbrain.
AB  - Most post-crossing commissural axons turn into longitudinal paths to make
      synaptic connections with their targets. Mechanisms that control their
      rostrocaudal turning polarity are still poorly understood. We used the hindbrain
      as a model system to investigate the rostral turning of a laterally located
      commissural tract, identified as the caudal group of contralateral cerebellar
      projecting second-order vestibular neurons (cC-VC). We found that the caudal
      hindbrain possessed a graded non-permissive/repulsive activity for growing cC-VC
      axons. This non-permissiveness/repulsion was in part mediated by glycosyl
      phosphatidylinositol (GPI)-anchored ephrin A. We further demonstrated that ephrin
      A2 was distributed in a caudal-high/rostral-low gradient in the caudolateral
      hindbrain and cC-VC axons expressed EphA receptors. Finally, perturbing ephrin
      A/EphA signalling both in vitro and in vivo led to rostrocaudal pathfinding
      errors of post-crossing cC-VC axons. These results suggest that ephrin A/EphA
      interactions play a key role in regulating the polarity of post-crossing cC-VC
      axons as they turn into the longitudinal axis.

PMID- 16968817
TI  - Megane/Heslike is required for normal GABAergic differentiation in the mouse
      superior colliculus.
AB  - The mouse Mgn protein (Helt) is structurally related to the neurogenic Drosophila
      hairy and Enhancer of split [h/E(spl)] proteins, but its unique structural
      properties distinguish it from other members of the family. Mgn expression shows
      a spatiotemporal correlation with GABAergic markers in several brain regions. We
      report here that homozygous Mgn-null mice die between the second and the fifth
      postnatal week of age, and show a complete depletion of Gad65 and Gad67
      expression in the superior colliculus and a reduction in the inferior colliculus.
      Other brain regions, as well as other neural systems, are not affected. The
      progenitor GABAergic cells appear to be generated in right numbers but fail to
      become GABAergic neurons. The phenotype of the mice is consistent with reduced
      GABAergic activity. Thus, our in vivo study provides evidence that Mgn is the key
      regulator of GABAergic neurons, controlling their specification in the dorsal
      midbrain. Another conclusion from our results is that the function of Mgn shows a
      previously unrecognized role for h/E(spl)-related transcription factors in the
      dorsal midbrain GABAergic cell differentiation. Vertebrate h/E(spl)-related genes
      can no longer be regarded solely as a factors that confer generic neurogenic
      properties, but as key components for the subtype-neuronal identity in the
      mammalian CNS.

PMID- 16968819
TI  - Exposure to Mycobacterium avium can modulate established immunity against
      Mycobacterium tuberculosis infection generated by Mycobacterium bovis BCG
      vaccination.
AB  - Mycobacterium bovis bacille Calmette Guerin (BCG), the current vaccine against
      infection with Mycobacterium tuberculosis, offers a variable, protective efficacy
      in man. It has been suggested that exposure to environmental mycobacteria can
      interfere with the generation of BCG-specific immunity. We hypothesized that
      exposure to environmental mycobacteria following BCG vaccination would interfere
      with established BCG immunity and reduce protective efficacy, thus modeling the
      guidelines for BCG vaccination within the first year of life. Mice were
      vaccinated with BCG and subsequently given repeated oral doses of live
      Mycobacterium avium to model exposure to environmental mycobacteria. The
      protective efficacy of BCG with and without subsequent exposure to M. avium was
      determined following an aerogenic challenge with M. tuberculosis. Exposure of BCG
      vaccinated mice to M. avium led to a persistent increase in the number of
      activated T cells within the brachial lymph nodes but similar T cell activation
      profiles in the lungs following infection with M. tuberculosis. The capacity of
      BCG-vaccinated mice to reduce the bacterial load following infection with M.
      tuberculosis was impaired in mice that had been exposed to M. avium. Our data
      suggest that exposure to environmental mycobacteria can negatively impact the
      protection afforded by BCG. These findings are relevant for the development of a
      vaccine administered in regions with elevated levels of environmental
      mycobacteria.

PMID- 16968818
TI  - MES-4: an autosome-associated histone methyltransferase that participates in
      silencing the X chromosomes in the C. elegans germ line.
AB  - Germ cell development in C. elegans requires that the X chromosomes be globally
      silenced during mitosis and early meiosis. We previously found that the nuclear
      proteins MES-2, MES-3, MES-4 and MES-6 regulate the different chromatin states of
      autosomes versus X chromosomes and are required for germline viability.
      Strikingly, the SET-domain protein MES-4 is concentrated on autosomes and
      excluded from the X chromosomes. Here, we show that MES-4 has histone H3
      methyltransferase (HMT) activity in vitro, and is required for histone H3K36
      dimethylation in mitotic and early meiotic germline nuclei and early embryos. MES
      4 appears unlinked to transcription elongation, thus distinguishing it from other
      known H3K36 HMTs. Based on microarray analysis, loss of MES-4 leads to
      derepression of X-linked genes in the germ line. We discuss how an autosomally
      associated HMT may participate in silencing genes on the X chromosome, in
      coordination with the direct silencing effects of the other MES proteins.

PMID- 16968821
TI  - Bell's palsy: a review of treatment using antiviral agents.
AB  - OBJECTIVE: To review the evidence evaluating the efficacy and safety of antiviral
      agents to reduce morbidity associated with Bell's palsy. DATA SOURCES: MEDLINE,
      EMBASE, and PubMed were searched (all up to April 2006) for English-language,
      prospective, randomized, controlled clinical trials that evaluated the use of
      antiviral agents in Bell's palsy. Search terms included Bell's palsy, acyclovir,
      valacyclovir, famciclovir, and randomized controlled trials. STUDY SELECTION AND
      DATA EXTRACTION: Prospective, randomized, controlled trials that evaluated
      efficacy and safety endpoints of antiviral agents in the treatment of Bell's
      palsy were included. Primary efficacy outcomes included facial paralysis recovery
      profile, facial paralysis recovery index, and the House-Brackmann facial nerve
      grading scale. Safety outcomes were also identified by each trial. DATA
      SYNTHESIS: Two prospective, randomized clinical trials were included in this
      review, both involving the use of acyclovir for treatment of Bell's palsy.
      Acyclovir monotherapy was shown to be inferior to prednisone monotherapy;
      however, the combination of acyclovir and prednisone was found to be superior to
      prednisone alone. There are limited data describing the safety of acyclovir in
      Bell's palsy. CONCLUSIONS: The use of acyclovir in the treatment of Bell's palsy
      remains controversial. Additional, adequately powered, randomized, placebo
      controlled trials are needed to definitively support its use. For the time being,
      the evidence reviewed in this article would favor the combination of acyclovir
      and prednisone if commenced within the first 72 hours of symptom onset.

PMID- 16968820
TI  - Cytolytic cells induce HMGB1 release from melanoma cell lines.
AB  - High mobility group box 1 (HMGB1) is one of the recently defined damage
      associated molecular pattern molecules, passively released from necrotic cells
      and secreted by activated macrophage/monocytes. Whether cytolytic cells induce
      HMGB1 release from tumor cells is not known. We developed a highly sensitive
      method for detecting intracellular HMGB1 in tumor cells, allowing analysis of the
      type of cell death and in particular, necrosis. We induced melanoma cell death
      with cytolytic lymphokine-activated killing (LAK) cells, tumor-specific cytolytic
      T lymphocytes, TRAIL, or granzyme B delivery and assessed intracellular HMGB1
      retention or release to investigate the mechanism of HMGB1 release by cytolytic
      cells. HMGB1 release from melanoma cells (451Lu, WM9) was detected within 4 h and
      24 h following incubation with IL-2-activated PBMC (LAK activity). HLA-A2 and
      MART1 or gp100-specific cytolytic T lymphocytes induced HMGB1 release from HLA-A2
      positive and MART1-positive melanoma cells (FEM X) or T2 cell-loaded, gp100
      specific peptides. TRAIL treatment, however, induced HMGB1 release, and it is
      interesting that this extrinsic pathway-mediated cell death was blocked with the
      pancaspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone.
      Conversely, granzyme B delivery did not induce HMGB1 release. HMGB1, along with
      other intracellular factors released from tumor cells induced by cytolysis, may
      be important components of the disordered tumor microenvironment. This has
      important implications for the immunotherapy of patients with cancer.
      Specifically, HMGB1 may promote healing or immune reactivity, depending on the
      nature of the local inflammatory response and the presence (or absence) of immune
      effectors.

PMID- 16968822
TI  - Concurrent use of metered-dose and dry powder inhalers by children with
      persistent asthma does not adversely affect spacer/inhaler technique.
AB  - BACKGROUND: Studies conducted in adults have suggested that patients who use a
      metered-dose inhaler/holding chamber spacer (MDI/S) and dry powder inhaler (DPI)
      concurrently will have poorer MDI/S technique than that of patients who use MDI/S
      exclusively. To our knowledge, as of August 31, 2006, no studies have been
      performed in pediatric patients. OBJECTIVE: To compare MDI/S technique scores of
      children using only MDI/S with scores of those using both MDI/S and DPIs.
      METHODS: The MDI/S technique of children aged 6-17 years, with persistent asthma,
      recruited from a general pediatric practice population for an asthma intervention
      study project was scored using a standardized checklist. MDI/S scores of children
      who were being treated with maintenance and rescue medication delivered only by
      MDI/S were compared with those treated with both MDI/S (rescue) and DPI
      (maintenance). Scores lower than 70% were considered to be inadequate. RESULTS: A
      total of 117 patients (73 male, 44 female), aged 9.70 +/- 3.1 years (mean +/-
      SD), with persistent asthma, participated in the study. There were 83 children
      (54 male, 29 female, age 9.4 +/- 3.2 y) in the MDI/S only group and 34 (19 male,
      15 female, age 10.3 +/- 2.9 y) in the MDI/S + DPI group. In the MDI/S + DPI
      group, Diskus was the DPI used for 32 patients, and Turbuhaler was used by 2
      children. Sixteen patients had severe persistent asthma, 80 had moderate
      persistent asthma, and 21 had mild persistent asthma as classified by National
      Heart Lung and Blood Institute guidelines. No difference in sex and age
      demographics existed; however, there was a difference in the distribution of
      asthma severity between groups (ie, no patients with mild persistent asthma in
      the MDI/S + DPI group; p < or = 0.01). Mean score for the MDI/S only group was 86
      +/- 17% and, for the MDI/S + DPI group, 90.1 +/- 12% (p = 0.15). More patients in
      the MDI/S group had inadequate scores (18%) compared with those in the MDI/S +
      DPI group (3%; p < 0.05). CONCLUSIONS: While DPI and MDI/S techniques are
      markedly different in several significant ways, concurrent use of these inhalers
      did not adversely affect MDI/S technique scores of pediatric patients with
      persistent asthma, compared with those using MDI/S alone. Patients in the MDI/S
      only group had an inadequate MDI/S score (<70%) more often than did patients in
      the MDI/S + DPI group.

PMID- 16968823
TI  - A comparative study of consumer participation in mental health pharmacy
      education.
AB  - BACKGROUND: People with mental illness have been recognized as key stakeholders
      in the development of mental health education. However, few studies have
      evaluated the impact of people with mental illness as participants in education
      programs for students studying to become health professionals. OBJECTIVE: To
      assess the impact of education provided by mental health consumer-educators on
      the attitudes of pharmacy students toward people with mental illness. METHODS:
      The study used a 2 group, nonrandomized, clustered, comparative design, with 4
      tutorial classes allocated to receive standard pharmacist-led instruction
      (comparison group), and 5 tutorial classes to receive standard pharmacist-led
      instruction plus additional input from mental health consumer-educators
      (intervention group). All pharmacy students (N = 229) enrolled in the third year
      of a 4 year pharmacy degree program were invited to participate. Consumer
      educators receiving ongoing treatment for illnesses including schizophrenia,
      bipolar disorder, and major depression participated in small-group work, case
      study discussions, and role plays with pharmacy students in the intervention
      group. Pharmacy students' attitudes were assessed using a 39 item survey
      instrument derived from previously published instruments evaluating social
      distance, attribution, provision of pharmaceutical services, and stigmatization
      of people with schizophrenia and severe depression. RESULTS: Paired baseline and
      follow-up responses were obtained from 117 students in the intervention group and
      94 students in the comparison group. Students who received the consumer
      intervention had decreased social distance scores (F(1209) = 5.30; p = 0.02).
      Students in the intervention group more strongly disagreed with 26 of 27
      nonsocial distance statements that demonstrated a negative attitude toward people
      with mental illness (F(1209) = 13.58; p < 0.001) and more strongly agreed with
      all 4 nonsocial distance statements that demonstrated a positive attitude
      (F(1209) = 7.56; p = 0.014). CONCLUSIONS: Consumer participation in mental health
      education for pharmacy students improves students' attitudes toward people with
      mental illness.

PMID- 16968824
TI  - Supplementary prescribing: early experiences of pharmacists in Great Britain.
AB  - BACKGROUND: Pharmacists in Great Britain can undertake supplementary prescribing
      (SP) after training at a higher education institution and completing a "period of
      learning in practice" in accordance with the Royal Pharmaceutical Society of
      Great Britain (RPSGB) curriculum. OBJECTIVE: To explore SP pharmacists' early
      experiences of prescribing and their perceptions of the prescribing course.
      METHODS: A questionnaire was mailed to all RPSGB prescribers (N = 518, on June 1,
      2005; 30 used in pilot questionnaire). Predictors of pharmacists starting to
      practice SP were identified in univariate analysis, and significant variables
      were further tested in multivariate analysis. RESULTS: The respondents (n = 401;
      82.2%) were mainly female (270; 67.3%), had more than 20 years' experience as a
      pharmacist (123; 30.7%), worked in hospital settings (160; 39.9%), and focused on
      cardiovascular conditions (143; 35.7%) during their period of learning in
      practice. The median course satisfaction score, on a scale of 3 to 15 (lowest to
      highest), was 10. Practicing SP was self-reported by 195 (48.6%) respondents, 154
      (79%) of whom had written a prescription. Ninety (58.4%) of the first
      prescriptions were written in primary care settings. Better patient management
      was regarded as the major benefit by 139 (71.3%) of those engaged in SP, while
      funding issues were identified by 71 (36.4%) as major barriers in implementing
      the practice. Lack of organizational recognition of SP was the main reason given
      (37; 18%) for those not commencing the practice. Independent predictors of those
      practicing SP included a longer time since registering as prescriber (p < 0.001);
      confidence of pharmacists in their prescribing abilities (p < 0.001); practicing
      in a setting other than community pharmacy (p = 0.001); and training in
      cardiovascular conditions or multiple conditions during the period of learning in
      practice (p = 0.005). CONCLUSIONS: Pharmacists have made progress in implementing
      SP, which is perceived by pharmacist prescribers as beneficial for both patients
      and themselves. Pharmacists need more support in terms of infrastructure and
      integration into the healthcare team to overcome some of the barriers to
      implementing SP.

PMID- 16968825
TI  - Clinical outcomes associated with concomitant use of atazanavir and proton pump
      inhibitors.
AB  - BACKGROUND: Pharmacokinetic studies have shown that the concomitant use of
      atazanavir and proton pump inhibitors (PPIs) decreases atazanavir plasma
      concentrations. Data describing clinical outcomes associated with this drug
      interaction are limited. OBJECTIVE: To describe the clinical outcomes, in terms
      of viral load (VL) suppression, associated with the concurrent use of ritonavir
      boosted or unboosted atazanavir and PPIs. METHODS: A retrospective chart review
      of 301 HIV-positive adults attending an Ohio infectious diseases clinic was
      performed to identify patients prescribed atazanavir, with or without ritonavir,
      and a PPI. The primary outcome was achievement/maintenance of VL less than 400
      copies/mL for 2 or more months during concomitant atazanavir and PPI therapies.
      Data collected included VL and CD4+ cell count at initiation of coadministered
      atazanavir and PPIs, genotype/phenotype, prior protease inhibitor experience,
      length of concurrent atazanavir/PPI therapy, and adherence. RESULTS: Twelve
      patients met inclusion criteria. PPIs and dosing regimens varied among subjects.
      Five of the subjects had a VL less than 400 copies/mL at initiation of
      atazanavir, with or without ritonavir, which was maintained during concurrent
      atazanavir and PPI therapy. Four additional subjects initiated protease inhibitor
      treatment with a VL greater than 400 copies/mL and achieved an undetectable VL
      while on concurrent PPI therapy. Duration of concurrent therapy ranged from 4 to
      23 months in these 9 subjects. Of the 3 patients not maintaining a VL less than
      400 copies/mL, 1 achieved that level at 4 months, and all 3 of these subjects
      showed atazanavir susceptibility during therapy per genotype resistance testing.
      Subsequently, decreased atazanavir susceptibility was reported in 1 of the 3
      patients after 18 months of therapy. Patients not achieving an undetectable VL
      had known adherence issues. CONCLUSIONS: In this case series, 9 of 12 subjects
      achieved successful virologic outcomes while receiving concurrent atazanavir and
      PPIs in a real-world environment. In our experience, the interaction between
      atazanavir and once-daily PPIs is not clinically significant for adherent
      patients. Concurrent use of these medications could be considered in patients
      with limited treatment options.

PMID- 16968826
TI  - Consumption of dietary supplements containing Citrus aurantium (bitter orange)-
      2004 California Behavioral Risk Factor Surveillance Survey (BRFSS).
AB  - BACKGROUND: Following the marketing ban of ephedra-containing supplements in
      April 2004, many manufacturers substituted the herb Citrus aurantium for ephedra
      and marketed the products as "ephedra-free" supplements. Extracts of C. aurantium
      contain synephrine, a sympathomimetic alkaloid. OBJECTIVE: To determine the
      prevalence of consumption of dietary supplements containing C. aurantium in
      California during 2004. METHODS: We used the 2004 California Behavioral Risk
      Factor Surveillance Survey to determine the prevalence of consumption of dietary
      supplements containing C. aurantium in California during 2004. RESULTS: Two
      percent (n = 70) of the 4140 survey respondents reported taking a dietary
      supplement containing C. aurantium in the previous year. Reasons stated included
      energy enhancement, weight loss, and appetite suppression. Compared with
      nonusers, users were more likely to report being single, aged 18-34 years, and
      Hispanic; consuming 3 or more alcoholic drinks on days that they imbibed; and
      having a heavier body mass index. Among the 5 users who reported experiencing an
      adverse event that they attributed to the supplement, 3 indicated that the
      severity was mild. CONCLUSIONS: Given that supplements containing ephedra were
      banned in April 2004, the results from this study may serve as a baseline
      estimate against which future studies of the use of C. aurantium products may be
      compared.

PMID- 16968827
TI  - Nitrofurantoin-induced fulminant hepatitis mimicking autoimmune hepatitis.

PMID- 16968828
TI  - Oxcarbazepine use in essential tremor.
AB  - OBJECTIVE: To report the novel finding of a significant improvement in essential
      tremor symptoms with oxcarbazepine in a patient with a suboptimal response to
      propranolol. CASE SUMMARY: A 40-year-old woman with a history of substance abuse
      complicated by essential tremor and neuropathic pain was admitted to our
      addictions unit with altered mental state due to escalating use of alprazolam.
      Alprazolam had been prescribed several months prior to admission for treatment of
      anxiety. The doses had risen to 5-10 mg/day during that period. Apparently, her
      essential tremor had responded inadequately to propranolol, but had responded
      well to alprazolam. She was started on a sedative/hypnotic withdrawal protocol,
      but did not require treatment with phenobarbital. She subsequently rated her
      tremor as "moderately severe." On discontinuation of the withdrawal protocol,
      oxcarbazepine 450 mg twice daily was initiated to treat her neuropathic pain, and
      the tremor improved, with a clinically significant reduction in tremor and a
      decreased pain score. DISCUSSION: Essential tremor is a common neurologic
      disorder with uncertain pathophysiology. Practice guidelines advocate the use of
      propranolol or primidone as first-line agents to treat essential tremor.
      Unfortunately, primidone has abuse potential and propranolol has variable
      pharmacokinetics; these characteristics limit their effectiveness in treating
      tremor. Our patient experienced a significant and sustained improvement in her
      tremor following the initiation of oxcarbazepine. To our knowledge, as of
      September 2, 2006, this is the first report of the use of oxcarbazepine in
      essential tremor. While the exact therapeutic action remains unclear,
      oxcarbazepine offers significant advantages compared with current first-line
      agents, including its good tolerability profile, the extended half-life of its
      metabolite, and lack of abuse potential. CONCLUSIONS: We report a case of
      essential tremor responding to oxcarbazepine. This drug offers several potential
      advantages over current first-line agents. Further research is warranted to test
      the robustness of this preliminary finding.

PMID- 16968829
TI  - Pharmacy continuing education: 40 years ago to now.

PMID- 16968830
TI  - COX-2 inhibitors, other NSAIDs, and cardiovascular risk: the seduction of common
      sense.

PMID- 16968833
TI  - The cover. Interior of the Palmhouse on the Pfaueninsel Near Potsdam.

PMID- 16968832
TI  - Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events:
      meta-analysis of randomized trials.
AB  - CONTEXT: Adverse effects of selective cyclooxygenase 2 (COX-2) inhibitors on
      renal events and arrhythmia have been controversial, with suggestions of a class
      effect. OBJECTIVE: To quantitatively evaluate adverse risks of renal events
      (renal dysfunction, hypertension, and peripheral edema) and arrhythmia events and
      to explore drug class effects and temporal trends of apparent effects of the COX
      2 inhibitors: rofecoxib, celecoxib, valdecoxib, parecoxib, etoricoxib, and
      lumiracoxib. DATA SOURCES: A systematic search of EMBASE and MEDLINE (through
      June 2006), bibliographies, US Food and Drug Administration reports, and
      pharmaceutical industry clinical trial databases. STUDY SELECTION: From relevant
      reports, 114 randomized double-blind clinical trials were included. DATA
      EXTRACTION: Information on publication year, participant characteristics, trial
      duration, drug, control, dose, and events were extracted using a standardized
      protocol. DATA SYNTHESIS: Results were pooled via random-effects models and meta
      regressions. Of 116 094 participants from 114 trial reports including 127 trial
      populations (40 rofecoxib, 37 celecoxib, 29 valdecoxib + parecoxib, 15
      etoricoxib, and 6 lumiracoxib), there were a total of 6394 composite renal events
      (2670 peripheral edema, 3489 hypertension, 235 renal dysfunction) and 286
      arrhythmia events. Results indicated significant heterogeneity of renal effects
      across agents (P for interaction = .02), indicating no class effect. Compared
      with controls, rofecoxib was associated with increased risk of arrhythmia
      (relative risk [RR], 2.90; 95% confidence interval [CI], 1.07-7.88) and composite
      renal events (RR, 1.53; 95% CI, 1.33-1.76); adverse renal effects increased with
      greater dose and duration (both P< or =.05). For all individual renal end points,
      rofecoxib was associated with increased risk of peripheral edema (RR, 1.43; 95%
      CI, 1.23-1.66), hypertension (RR, 1.55; 95% CI, 1.29-1.85), and renal dysfunction
      (RR, 2.31; 95% CI, 1.05-5.07). In contrast, celecoxib was associated with lower
      risk of both renal dysfunction (RR, 0.61; 95% CI, 0.40-0.94) and hypertension
      (RR, 0.83; 95% CI, 0.71-0.97) compared with controls. Other agents were not
      significantly associated with risk. Time-cumulative analyses indicated that for
      rofecoxib the adverse risks for peripheral edema and hypertension were evident by
      the end of year 2000 and for risk of arrhythmia by 2004. CONCLUSIONS: In this
      comprehensive analysis of 114 randomized trials with 116,094 participants,
      rofecoxib was associated with increased renal and arrhythmia risks. A COX-2
      inhibitor class effect was not evident. Future safety monitoring is warranted and
      may benefit from an active and continuous cumulative surveillance system.

PMID- 16968831
TI  - Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the
      observational studies of selective and nonselective inhibitors of cyclooxygenase
      2.
AB  - CONTEXT: Evidence that rofecoxib increases the risk of myocardial infarction has
      led to scrutiny of other nonsteroidal anti-inflammatory drugs (NSAIDs).
      Regulatory agencies have provided variable advice regarding the cardiovascular
      risks with older nonselective NSAIDs. OBJECTIVE: To undertake a systematic review
      and meta-analysis of controlled observational studies to compare the risks of
      serious cardiovascular events with individual NSAIDs and cyclooxygenase 2
      inhibitors. DATA SOURCES: Searches were conducted of electronic databases (1985
      2006), scientific meeting proceedings, epidemiological research Web sites, and
      bibliographies of eligible studies. STUDY SELECTION: Eligible studies were of
      case-control or cohort design, reported on cardiovascular events (predominantly
      myocardial infarction) with cyclooxygenase 2 inhibitor, NSAID use, or both with
      nonuse/remote use of the drugs as the reference exposure. Of 7086 potentially
      eligible titles, 17 case-control and 6 cohort studies were included. Thirteen
      studies reported on cyclooxygenase 2 inhibitors, 23 on NSAIDs, and 13 on both
      groups of drugs. DATA EXTRACTION: Two people independently extracted data and
      assessed study quality with disagreements resolved by consensus. DATA SYNTHESIS:
      Data were combined using a random-effects model. A dose-related risk was evident
      with rofecoxib, summary relative risk with 25 mg/d or less, 1.33 (95% confidence
      interval [CI], 1.00-1.79) and 2.19 (95% CI, 1.64-2.91) with more than 25 mg/d.
      The risk was elevated during the first month of treatment. Celecoxib was not
      associated with an elevated risk of vascular occlusion, summary relative risk
      1.06 (95% CI, 0.91-1.23). Among older nonselective drugs, diclofenac had the
      highest risk with a summary relative risk of 1.40 (95% CI, 1.16-1.70). The other
      drugs had summary relative risks close to 1: naproxen, 0.97 (95% CI, 0.87-1.07);
      piroxicam, 1.06 (95% CI, 0.70-1.59); and ibuprofen, 1.07 (95% CI, 0.97-1.18).
      CONCLUSIONS: This review confirms the findings from randomized trials regarding
      the risk of cardiovascular events with rofecoxib and suggests that celecoxib in
      commonly used doses may not increase the risk, contradicts claims of a protective
      effect of naproxen, and raises serious questions about the safety of diclofenac,
      an older drug.

PMID- 16968834
TI  - A piece of my mind. Triggers.

PMID- 16968835
TI  - Health research funding losing ground.

PMID- 16968836
TI  - Advances seen in mood disorders research.

PMID- 16968837
TI  - Treatment key to reducing cost of crime.

PMID- 16968838
TI  - Researchers focus on alternatives for diagnosing heart disease in women.

PMID- 16968839
TI  - Stroke risk emphasized in atrial fibrillation guidelines.

PMID- 16968840
TI  - Antiarrhythmic therapy for prevention of implantable cardioverter defibrillator
      shocks.

PMID- 16968841
TI  - Antiarrhythmic therapy for prevention of implantable cardioverter defibrillator
      shocks.

PMID- 16968842
TI  - Abstract acceptance and blinded peer review.

PMID- 16968843
TI  - Effects of differences between peer reviewers suggested by authors and by
      editors.

PMID- 16968844
TI  - Remission of maternal depression and children's psychopathology.

PMID- 16968845
TI  - Remission of maternal depression and children's psychopathology.

PMID- 16968846
TI  - Remission of maternal depression and children's psychopathology.

PMID- 16968847
TI  - Wait-and-see prescription for the treatment of acute otitis media: a randomized
      controlled trial.
AB  - CONTEXT: Acute otitis media (AOM) is the most common diagnosis for which
      antibiotics are prescribed for children. Previous trials that have evaluated a
      "wait-and-see prescription" (WASP) for antibiotics, with which parents are asked
      not to fill the prescription unless the child either is not better or is worse in
      48 hours, have excluded children with severe AOM. None of these trials were
      conducted in an emergency department. OBJECTIVES: To determine whether treatment
      of AOM using a WASP significantly reduces use of antibiotics compared with a
      "standard prescription" (SP) and to evaluate the effects of this intervention on
      clinical symptoms and adverse outcomes related to antibiotic use. DESIGN,
      SETTING, AND PATIENTS: A randomized controlled trial conducted between July 12,
      2004, and July 11, 2005. Children with AOM aged 6 months to 12 years seen in an
      emergency department were randomly assigned to receive either a WASP or an SP.
      All patients received ibuprofen and otic analgesic drops for use at home. A
      research assistant, blinded to group assignment, conducted structured phone
      interviews 4 to 6, 11 to 14, and 30 to 40 days after enrollment to determine
      outcomes. MAIN OUTCOME MEASURES: Filling of the antibiotic prescription and
      clinical course. RESULTS: Overall, 283 patients were randomized either to the
      WASP group (n = 138) or the SP group (n = 145). Substantially more parents in the
      WASP group did not fill the antibiotic prescription (62% vs 13%; P<.001). There
      was no statistically significant difference between the groups in the frequency
      of subsequent fever, otalgia, or unscheduled visits for medical care. Within the
      WASP group, both fever (relative risk [RR], 2.95; 95% confidence interval [CI],
      1.75 - 4.99; P<.001) and otalgia (RR, 1.62; 95% CI, 1.26 - 2.03; P<.001) were
      associated with filling the prescription. CONCLUSION: The WASP approach
      substantially reduced unnecessary use of antibiotics in children with AOM seen in
      an emergency department and may be an alternative to routine use of
      antimicrobials for treatment of such children. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00250900.

PMID- 16968848
TI  - Regression of electrocardiographic left ventricular hypertrophy and decreased
      incidence of new-onset atrial fibrillation in patients with hypertension.
AB  - CONTEXT: Atrial fibrillation (AF) is associated with increased risk of mortality
      and cardiovascular events, particularly stroke, making prevention of new-onset AF
      a clinical priority. Although the presence and severity of electrocardiographic
      left ventricular hypertrophy (LVH) appear to predict development of AF, whether
      regression of electrocardiographic LVH is associated with a decreased incidence
      of AF is unclear. OBJECTIVE: To test the hypothesis that in-treatment regression
      or continued absence of electrocardiographic LVH during antihypertensive therapy
      is associated with a decreased incidence of AF, independent of blood pressure and
      treatment modality. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized,
      parallel-group study conducted in 1995-2001 among 8831 men and women with
      hypertension, aged 55-80 years (median, 67 years), with electrocardiographic LVH
      by Cornell voltage-duration product or Sokolow-Lyon voltage, with no history of
      AF, without AF on the baseline electrocardiogram, and enrolled in the Losartan
      Intervention for Endpoint Reduction in Hypertension Study. INTERVENTIONS:
      Losartan- or atenolol-based treatment regimens, with follow-up assessments at 6
      months and then yearly until death or study end. MAIN OUTCOME MEASURE: New-onset
      AF in relation to electrocardiographic LVH determined at baseline and
      subsequently. Electrocardiographic LVH was measured using sex-adjusted Cornell
      product criteria ({R(aVL) + S(V3) [+ 6 mm in women]} x QRS duration). RESULTS:
      After a mean (SD) follow-up of 4.7 (1.1) years, new-onset AF occurred in 290
      patients with in-treatment regression or continued absence of Cornell product LVH
      for a rate of 14.9 per 1000 patient-years and in 411 patients with in-treatment
      persistence or development of LVH by Cornell product criteria for a rate of 19.0
      per 1000 patient-years. In time-dependent Cox analyses adjusted for treatment
      effects, baseline differences in risk factors for AF, baseline and in-treatment
      blood pressure, and baseline severity of electrocardiographic LVH, lower in
      treatment Cornell product LVH treated as a time-varying covariate was associated
      with a 12.4% lower rate of new-onset AF (adjusted hazard ratio [HR], 0.88; 95%
      CI, 0.80-0.97; P = .007) for every 1050 mm x msec (per 1-SD) lower Cornell
      product, with persistence of the benefit of losartan vs atenolol therapy on
      developing AF (HR, 0.83; 95% CI, 0.71-0.97; P = .01). CONCLUSIONS: Lower Cornell
      product electrocardiographic LVH during antihypertensive therapy is associated
      with a lower likelihood of new-onset AF, independent of blood pressure lowering
      and treatment modality in essential hypertension. These findings suggest that
      antihypertensive therapy targeted at regression or prevention of
      electrocardiographic LVH may reduce the incidence of new-onset AF.

PMID- 16968849
TI  - Risk of aborted cardiac arrest or sudden cardiac death during adolescence in the
      long-QT syndrome.
AB  - CONTEXT: Analysis of predictors of cardiac events in hereditary long-QT syndrome
      (LQTS) has primarily considered syncope as the predominant end point. Risk
      factors specific for aborted cardiac arrest and sudden cardiac death have not
      been investigated. OBJECTIVE: To identify risk factors associated with aborted
      cardiac arrest and sudden cardiac death during adolescence in patients with
      clinically suspected LQTS. DESIGN, SETTING, AND PARTICIPANTS: The study involved
      2772 participants from the International Long QT Syndrome Registry who were alive
      at age 10 years and were followed up during adolescence until age 20 years. The
      registry enrollment began in 1979 at 5 cardiology centers in the United States
      and Europe. MAIN OUTCOME MEASURES: Aborted cardiac arrest or LQTS-related sudden
      cardiac death; follow-up ended on February 15, 2005. RESULTS: There were 81
      patients who experienced aborted cardiac arrest and 45 who had sudden cardiac
      death; 9 of the 81 patients who had an aborted cardiac arrest event experienced
      subsequent sudden cardiac death. Significant independent predictors of aborted
      cardiac arrest or sudden cardiac death during adolescence included recent
      syncope, QTc interval, and sex. Compared with those with no syncopal events in
      the last 10 years, patients with 1 or 2 or more episodes of syncope 2 to 10 years
      ago (but none in the last 2 years) had an adjusted hazard ratio (HR) of 2.7; (95%
      confidence interval [CI], 1.3-5.7; P<.01) and an adjusted HR of 5.8 (95% CI, 3.6
      9.4; P<.001), respectively, for life-threatening events; those with 1 syncopal
      episodes in the last 2 years had an adjusted HR of 11.7 (95% CI, 7.0-19.5;
      P<.001) and those with 2 or more syncopal episodes in the last 2 years had an
      adjusted HR of 18.1 (95% CI, 10.4-31.2; P<.001). Irrespective of events occurring
      more than 2 years ago, QTc of 530 ms or longer was associated with increased risk
      (adjusted HR, 2.3; 95% CI, 1.6-3.3; P<.001) compared with those having a shorter
      QTc. Males between the ages of 10 and 12 years had higher risk than females (HR,
      4.0; 95% CI, 1.8-9.2; P = .001), but there was no significant risk difference
      between males and females between the ages of 13 and 20 years. Among individuals
      with syncope in the past 2 years, beta-blocker therapy was associated with a 64%
      reduced risk (HR, 0.36; 95% CI, 0.18-0.72; P<.01). CONCLUSIONS: In LQTS, the
      timing and frequency of syncope, QTc prolongation, and sex were predictive of
      risk for aborted cardiac arrest and sudden cardiac death during adolescence.
      Among patients with recent syncope, beta-blocker treatment was associated with
      reduced risk.

PMID- 16968850
TI  - Green tea consumption and mortality due to cardiovascular disease, cancer, and
      all causes in Japan: the Ohsaki study.
AB  - CONTEXT: Green tea polyphenols have been extensively studied as cardiovascular
      disease and cancer chemopreventive agents in vitro and in animal studies.
      However, the effects of green tea consumption in humans remain unclear.
      OBJECTIVE: To investigate the associations between green tea consumption and all
      cause and cause-specific mortality. DESIGN, SETTING, AND PARTICIPANTS: The Ohsaki
      National Health Insurance Cohort Study, a population-based, prospective cohort
      study initiated in 1994 among 40,530 Japanese adults aged 40 to 79 years without
      history of stroke, coronary heart disease, or cancer at baseline. Participants
      were followed up for up to 11 years (1995-2005) for all-cause mortality and for
      up to 7 years (1995-2001) for cause-specific mortality. MAIN OUTCOME MEASURES:
      Mortality due to cardiovascular disease, cancer, and all causes. RESULTS: Over 11
      years of follow-up (follow-up rate, 86.1%), 4209 participants died, and over 7
      years of follow-up (follow-up rate, 89.6%), 892 participants died of
      cardiovascular disease and 1134 participants died of cancer. Green tea
      consumption was inversely associated with mortality due to all causes and due to
      cardiovascular disease. The inverse association with all-cause mortality was
      stronger in women (P = .03 for interaction with sex). In men, the multivariate
      hazard ratios of mortality due to all causes associated with different green tea
      consumption frequencies were 1.00 (reference) for less than 1 cup/d, 0.93 (95%
      confidence interval [CI], 0.83-1.05) for 1 to 2 cups/d, 0.95 (95% CI, 0.85-1.06)
      for 3 to 4 cups/d, and 0.88 (95% CI, 0.79-0.98) for 5 or more cups/d,
      respectively (P = .03 for trend). The corresponding data for women were 1.00,
      0.98 (95% CI, 0.84-1.15), 0.82 (95% CI, 0.70-0.95), and 0.77 (95% CI, 0.67-0.89),
      respectively (P<.001 for trend). The inverse association with cardiovascular
      disease mortality was stronger than that with all-cause mortality. This inverse
      association was also stronger in women (P = .08 for interaction with sex). In
      women, the multivariate hazard ratios of cardiovascular disease mortality across
      increasing green tea consumption categories were 1.00, 0.84 (95% CI, 0.63-1.12),
      0.69 (95% CI, 0.52-0.93), and 0.69 (95% CI, 0.53-0.90), respectively (P = .004
      for trend). Among the types of cardiovascular disease mortality, the strongest
      inverse association was observed for stroke mortality. In contrast, the hazard
      ratios of cancer mortality were not significantly different from 1.00 in all
      green tea categories compared with the lowest-consumption category. CONCLUSION:
      Green tea consumption is associated with reduced mortality due to all causes and
      due to cardiovascular disease but not with reduced mortality due to cancer.

PMID- 16968851
TI  - Peer-reviewed publication of clinical trials completed for pediatric exclusivity.
AB  - CONTEXT: Much of pediatric drug use is off-label because appropriate pediatric
      studies have not been conducted and the drugs have not been labeled by the US
      Food and Drug Administration (FDA) for use in children. In 1997, Congress
      authorized the FDA to grant extensions of marketing rights known as "pediatric
      exclusivity" if FDA-requested pediatric trials were conducted. As a result, there
      have been over 100 product labeling changes. The publication status of studies
      completed for pediatric exclusivity has not been evaluated. OBJECTIVE: To
      quantify the dissemination of results of studies conducted for pediatric
      exclusivity into the peer-review literature. DESIGN: Cohort study of all trials
      conducted for pediatric exclusivity between 1998 and 2004 as determined by
      MEDLINE and EMBASE searches through 2005, the subsequent labeling changes, and
      the publication of those studies in peer-reviewed journals. We categorized any
      labeling changes resulting from the studies as positive or negative for the drug
      under study. We then evaluated aspects of the studies and product label changes
      that were associated with subsequent publication in peer-reviewed medical
      journals. MAIN OUTCOME MEASURES: Publication of the trial data in peer-reviewed
      journals. RESULTS: Between 1998 and 2004, 253 studies were submitted to the FDA
      for pediatric exclusivity: 125 (50%) evaluated efficacy, 51 (20%) were multi-dose
      pharmacokinetic, 34 (13%) were single-dose pharmacokinetic, and 43 (17%) were
      safety studies. Labeling changes were positive for 127/253 (50%) of studies; only
      113/253 (45%) were published. Efficacy studies and those with a positive labeling
      change were more likely to be published. CONCLUSIONS: The pediatric exclusivity
      program has been successful in encouraging drug studies in children. However, the
      dissemination of these results in the peer-reviewed literature is limited.
      Mechanisms to more widely disperse this information through publication warrant
      further evaluation.

PMID- 16968852
TI  - Does this patient with headache have a migraine or need neuroimaging?
AB  - CONTEXT: In assessing the patient with headache, clinicians are often faced with
      2 important questions: Is this headache a migraine? Does this patient require
      neuroimaging? The diagnosis of migraine can direct therapy, and information
      obtained from the history and physical examination is used by physicians to
      determine which patients require neuroimaging. OBJECTIVE: To determine the
      usefulness of the history and physical examination that distinguish patients with
      migraine from those with other headache types and that identify those patients
      who should undergo neuroimaging. DATA SOURCES AND STUDY SELECTION: A systematic
      review was performed using articles from MEDLINE (1966-November 2005) that
      assessed the performance characteristics of screening questions in diagnosing
      migraine (with the International Headache Society diagnostic criteria as a gold
      standard) and addressed the accuracy of the clinical examination in predicting
      the presence of underlying intracranial pathology (with computed
      tomography/magnetic resonance imaging as the reference standard). DATA
      EXTRACTION: Two authors independently reviewed each study to determine
      eligibility, abstract data, and classify methodological quality using
      predetermined criteria. Disagreement was resolved by consensus with a third
      author. DATA SYNTHESIS: Four studies of screening questions for migraine (n =
      1745 patients) and 11 neuroimaging studies (n = 3725 patients) met inclusion
      criteria. All 4 of the migraine studies illustrated high sensitivity and
      specificity if 3 or 4 criteria were met. The best predictors can be summarized by
      the mnemonic POUNDing (Pulsating, duration of 4-72 hOurs, Unilateral, Nausea,
      Disabling). If 4 of the 5 criteria are met, the likelihood ratio (LR) for
      definite or possible migraine is 24 (95% confidence interval [CI], 1.5-388); if 3
      are met, the LR is 3.5 (95% CI, 1.3-9.2), and if 2 or fewer are met, the LR is
      0.41 (95% CI, 0.32-0.52). For the neuroimaging question, several clinical
      features were found on pooled analysis to predict the presence of a serious
      intracranial abnormality: cluster-type headache (LR, 10.7; 95% CI, 2.2-52);
      abnormal findings on neurologic examination (LR, 5.3; 95% CI, 2.4-12); undefined
      headache (ie, not cluster-, migraine-, or tension-type) (LR, 3.8; 95% CI, 2.0
      7.1); headache with aura (LR, 3.2; 95% CI, 1.6-6.6); headache aggravated by
      exertion or a valsalva-like maneuver (LR, 2.3; 95% CI, 1.4-3.8); and headache
      with vomiting (LR, 1.8; 95% CI, 1.2-2.6). No clinical features were useful in
      ruling out significant pathologic conditions. CONCLUSIONS: The presence of 4
      simple historical features can accurately diagnose migraine. Several individual
      clinical features were found to be associated with a significant intracranial
      abnormality, and patients with these features should undergo neuroimaging.

PMID- 16968853
TI  - Moderators of treatment outcomes: clinical, research, and policy importance.

PMID- 16968855
TI  - Delayed prescribing--a sensible approach to the management of acute otitis media.

PMID- 16968856
TI  - JAMA patient page. Electrocardiograms.

PMID- 16968857
TI  - Microsatellite documentation of male-mediated outcrossing between inbred
      laboratory strains of the self-fertilizing mangrove killifish (Kryptolebias
      Marmoratus).
AB  - Primers for 36 microsatellite loci were developed and employed to characterize
      genetic stocks and detect possible outcrossing between highly inbred laboratory
      strains of the self-fertilizing mangrove killifish, Kryptolebias marmoratus. From
      attempted crosses involving hermaphrodites from particular geographic strains and
      gonochoristic males from others, 2 among a total of 32 surveyed progenies (6.2%)
      displayed multilocus heterozygosity clearly indicative of interstrain gametic
      syngamy. One of these outcross hybrids was allowed to resume self-fertilization,
      and microsatellite assays of progeny showed that heterozygosity decreased by
      approximately 50% after one generation, as expected. Although populations of K.
      marmoratus consist mostly of synchronous hermaphrodites with efficient mechanisms
      of internal self-fertilization, these laboratory findings experimentally confirm
      that conspecific males can mediate occasional outcross events and that this
      process can release extensive genic heterozygosity.

PMID- 16968858
TI  - Re: "Fetal growth and childhood behavioral problems: Results from the ALSPAC
      cohort".

PMID- 16968860
TI  - Invited commentary: Using area-based socioeconomic measures--think conceptually,
      act cautiously.

PMID- 16968859
TI  - The metabolic syndrome is associated with reduced risk of prostate cancer.
AB  - Diabetes is associated with reduced risk of prostate cancer, but whether the
      metabolic syndrome is associated with prostate cancer is not established. The
      authors assessed this association in the Atherosclerosis Risk in Communities
      (ARIC) Study, comprising 6,429 men in four US communities initially with no
      history of cancer and aged 45-64 years. Metabolic syndrome and other risk factors
      were assessed in 1987-1989. Follow-up for prostate cancer incidence (n = 385
      through 2000) was accomplished through cancer registry and hospital linkage. At
      baseline, 1,871 men (29.5%) had the metabolic syndrome. After the authors
      adjusted for other risk factors, men with the metabolic syndrome (> or =3
      components) were significantly less likely to develop prostate cancer (relative
      risk = 0.77, 95% confidence interval: 0.60, 0.98) than men without the metabolic
      syndrome. Diabetes was negatively associated with prostate cancer, although the
      confidence interval included 1 (relative risk = 0.73, 95% confidence interval:
      0.51, 1.05). When diabetic participants were excluded, the inverse association
      between metabolic syndrome and prostate cancer incidence was slightly
      strengthened. In this study, the metabolic syndrome was associated with decreased
      prostate cancer incidence. The authors hypothesize that this finding reflects a
      decrease in bioavailable (free and albumin-bound) testosterone with the metabolic
      syndrome and a concomitant reduction in prostate cancer risk.

PMID- 16968861
TI  - Address-based versus random-digit-dial surveys: comparison of key health and risk
      indicators.
AB  - Use of random-digit dialing (RDD) for conducting health surveys is increasingly
      problematic because of declining participation rates and eroding frame coverage.
      Alternative survey modes and sampling frames may improve response rates and
      increase the validity of survey estimates. In a 2005 pilot study conducted in six
      states as part of the Behavioral Risk Factor Surveillance System, the authors
      administered a mail survey to selected household members sampled from addresses
      in a US Postal Service database. The authors compared estimates based on data
      from the completed mail surveys (n = 3,010) with those from the Behavioral Risk
      Factor Surveillance System telephone surveys (n = 18,780). The mail survey data
      appeared reasonably complete, and estimates based on data from the two survey
      modes were largely equivalent. Differences found, such as differences in the
      estimated prevalences of binge drinking (mail = 20.3%, telephone = 13.1%) or
      behaviors linked to human immunodeficiency virus transmission (mail = 7.1%,
      telephone = 4.2%), were consistent with previous research showing that, for
      questions about sensitive behaviors, self-administered surveys generally produce
      higher estimates than interviewer-administered surveys. The mail survey also
      provided access to cell-phone-only households and households without telephones,
      which cannot be reached by means of standard RDD surveys.

PMID- 16968862
TI  - Prevalence and determinants of lateral and medial epicondylitis: a population
      study.
AB  - Epicondylitis is a common disorder of the arm, yet the role of individual- and
      work-related factors has not been addressed in a population study. The aims of
      this study were to estimate the prevalence of lateral and medial epicondylitis
      and to investigate their risk factors. The target population of this study
      comprised a representative sample of people aged 30-64 years residing in Finland
      during 2000-2001. Of the 5,871 subjects, 4,783 (81.5%) were included in this
      study. The prevalence of definite lateral epicondylitis was 1.3%, and that of
      medial epicondylitis was 0.4%. The prevalence did not differ between men and
      women and was highest in subjects aged 45-54 years. Current smoking (adjusted
      odds ratio (OR) = 3.4, 95% confidence interval (CI): 1.4, 8.3) and former smoking
      (OR = 3.0, 95% CI: 1.3, 6.6) were associated with definite lateral epicondylitis.
      An interaction (p = 0.002) was found between repetitive movements of the arms and
      forceful activities for the risk of possible or definite lateral epicondylitis
      (for both repetitive and forceful activities vs. no such activity: OR = 5.6, 95%
      CI: 1.9, 16.5). Smoking, obesity, repetitive movements, and forceful activities
      independently of each other showed significant associations with medial
      epicondylitis. Epicondylitis is relatively common among working-age individuals
      in the general population. Physical load factors, smoking, and obesity are strong
      determinants of epicondylitis.

PMID- 16968863
TI  - Using data on social contacts to estimate age-specific transmission parameters
      for respiratory-spread infectious agents.
AB  - The estimation of transmission parameters has been problematic for diseases that
      rely predominantly on transmission of pathogens from person to person through
      small infectious droplets. Age-specific transmission parameters determine how
      such respiratory agents will spread among different age groups in a human
      population. Estimating the values of these parameters is essential in planning an
      effective response to potentially devastating pandemics of smallpox or influenza
      and in designing control strategies for diseases such as measles or mumps. In
      this study, the authors estimated age-specific transmission parameters by
      augmenting infectious disease data with auxiliary data on self-reported numbers
      of conversational partners per person. They show that models that use
      transmission parameters based on these self-reported social contacts are better
      able to capture the observed patterns of infection of endemically circulating
      mumps, as well as observed patterns of spread of pandemic influenza. The
      estimated age-specific transmission parameters suggested that school-aged
      children and young adults will experience the highest incidence of infection and
      will contribute most to further spread of infections during the initial phase of
      an emerging respiratory-spread epidemic in a completely susceptible population.
      These findings have important implications for controlling future outbreaks of
      novel respiratory-spread infectious agents.

PMID- 16968864
TI  - In utero exposure to background concentrations of DDT and cognitive functioning
      among preschoolers.
AB  - p,p'-DDT (bis[p-chlorophenyl]-1,1,1-trichloroethane) is a persistent
      organochlorine compound that has been used worldwide as an insecticide. The
      authors evaluated the association of cord serum levels of DDT and its metabolite,
      2,2-bis(p-chlorophenyl)-1,1-dichloroethylene (DDE), with neurodevelopment at age
      4 years. Two birth cohorts in Ribera d'Ebre and Menorca (Spain) were recruited
      between 1997 and 1999 (n = 475). Infants were assessed at age 4 years by using
      the McCarthy Scales of Children's Abilities. Organochlorine compounds were
      measured in cord serum. Children's diet and parental sociodemographic information
      was obtained through questionnaire. Results showed that DDT cord serum
      concentration at birth was inversely associated with verbal, memory,
      quantitative, and perceptual-performance skills at age 4 years. Children whose
      DDT concentrations in cord serum were >0.20 ng/ml had mean decreases of 7.86
      (standard error, 3.21) points in the verbal scale and 10.86 (standard error,
      4.33) points in the memory scale when compared with children whose concentrations
      were <0.05 ng/ml. These associations were stronger among girls. Prenatal exposure
      to background, low-level concentrations of DDT was associated with a decrease in
      preschoolers' cognitive skills. These results should be considered when
      evaluating the risk and benefits of spraying DDT during antimalaria and other
      disease-vector campaigns.

PMID- 16968865
TI  - Dietary fat and risk of postmenopausal breast cancer in a 20-year follow-up.
AB  - Dietary fat in midlife has not been associated with breast cancer risk in most
      studies, but few have followed women beyond one decade. The authors examined the
      relation of dietary fat, assessed by repeated questionnaires, to incidence of
      postmenopausal breast cancer in a cohort of 80,375 US women (3,537 new cases)
      prospectively followed for 20 years between 1980 and 2000. The multivariable
      relative risk for an increment of 5% of energy from total dietary fat intake was
      0.98 (95% confidence interval: 0.95, 1.00). Additionally, specific types of fat
      were not associated with an increased risk of breast cancer. Furthermore,
      secondary analyses indicated no differences in breast cancer risk by estrogen
      receptor or progesterone receptor status. However, stratification by waist
      circumference indicated a significant decrease in breast cancer risk for
      participants with a waist circumference of 35 inches (88.9 cm) or greater (p
      trend = 0.04). None of the latency intervals investigated were associated with an
      increased risk of breast cancer. In addition, fat intake before menopause was not
      related to risk of postmenopausal breast cancer. These results suggest a
      reduction in breast cancer risk for women with insulin resistance syndrome who
      consume high-fat diets and no association between specific sources of fat during
      midlife and risk of postmenopausal breast cancer.

PMID- 16968866
TI  - Comparing individual- and area-based socioeconomic measures for the surveillance
      of health disparities: A multilevel analysis of Massachusetts births, 1989-1991.
AB  - The absence of individual-level socioeconomic information in most US health
      surveillance data necessitates using area-based socioeconomic measures (ABSMs) to
      monitor health inequalities. Using the 1989-1991 birth weight data from
      Massachusetts, the authors compared estimates of health disparities detected with
      census tract- and block group-level ABSMs pertaining to poverty and education, as
      well as parental education, both independently and together. In separate models,
      adjusted for infant's sex, mother's age, and parents' race/ethnicity, worst-off
      categories of census tract ABSMs and parental education had a comparable birth
      weight deficit of approximately 70 g. Similar results were observed for low birth
      weight (<2,500 g), with worst-off categories of census tract ABSMs and parental
      education having an odds ratio of approximately 1.37 (p < 0.001). In mutually
      adjusted models for birth weight and low birth weight, census tract ABSMs still
      detected an effect estimate nearly 50% of that detected by parental education.
      Additionally, census tract ABSMs detected socioeconomic gradients in birth weight
      among births to mothers aged less than 25 years, an age group in which
      educational attainment is unlikely to be completed. These results suggest that
      aptly chosen ABSMs can be used to monitor socioeconomic inequalities in health.
      The risk, if any, in the absence of individual-level socioeconomic information is
      a conservative estimate of socioeconomic inequalities in health.

PMID- 16968867
TI  - Invited commentary: Challenges of using contact data to understand acute
      respiratory disease transmission.

PMID- 16968868
TI  - Two distinct functional networks for successful resolution of proactive
      interference.
AB  - In proactive interference (PI) paradigms, previous learning impairs the
      acquisition of new, related information. In rats, efficient resolution of PI
      relies on cholinergic modulation from the basal forebrain (BF). To test whether
      humans resolve PI using a functional network dependent on the medial
      septum/diagonal band of Broca (MS/DB) nuclei of the BF, we analyzed functional
      magnetic resonance imaging signal recorded while human participants learned to
      respond to baseline color paired associates and then additional pairs that
      interfered with the baseline pairs. Multivariate, partial least-squares analysis
      supported a MS/DB-dependent functional network: MS/DB activity covaried with
      activity in areas important to selective attention, including intraparietal
      sulcus, and memory that are direct cholinergic efferents of the MS/DB, including
      the hippocampus, as well as the ventrolateral prefrontal cortex, implicated in PI
      resolution. This network was associated with effective PI-resolution behavior. A
      second network also correlated with PI resolution but appearing not to be driven
      by the MS/DB, included the lateral orbitofrontal cortex. Patients with
      compromised BF function did not engage the MS/DB-dependent network reliably;
      instead their PI-resolution behavior was well explained by the second network.
      Thus, 2 functional networks may underly a single cognitive function; when the
      MS/DB-dependent attention/memory integration network is compromised, an alternate
      network is available to maintain normal levels of performance.

PMID- 16968869
TI  - Multisensory interactions within human primary cortices revealed by BOLD
      dynamics.
AB  - Whether signals from different sensory modalities converge and interact within
      primary cortices in humans is unresolved, despite emerging evidence in animals.
      This is partially because of debates concerning the appropriate analyses of
      functional magnetic resonance imaging (fMRI) data in response to multisensory
      phenomena. Using event-related fMRI, we observed that simple auditory stimuli
      (noise bursts) activated primary visual cortices and that simple visual stimuli
      (checkerboards) activated primary auditory cortices, indicative of multisensory
      convergence. Moreover, analyses of blood oxygen level-dependent response dynamics
      revealed facilitation of hemodynamic response peak latencies and slopes for
      multisensory auditory-visual stimuli versus either unisensory condition,
      indicative of multisensory interactions within primary sensory cortices. Neural
      processing at the lowest cortical levels can be modulated by interactions between
      the senses. Temporal information in fMRI data can reveal these modulations and
      overcome analytic and interpretational challenges of more traditional procedures.
      In addition to providing an essential translational link with animal models,
      these results suggest that longstanding notions of cortical organization need to
      be revised to include multisensory interactions as an inherent component of
      functional brain organization.

PMID- 16968870
TI  - Deterioration of academic achievement and marijuana use onset among rural
      adolescents.
AB  - This study utilizes discrete-time survival analysis to assess the effect of level
      of academic achievement (both contemporaneously and prospectively) and changes in
      academic achievement on initiation of marijuana use among rural adolescents in
      junior high school. In the sample under consideration, 36% of boys and 23% of
      girls initiated use of marijuana by the end of ninth grade. Consistent with our
      hypothesis, poor academic achievement is a salient predictor of initiation of
      marijuana use among both boys and girls. Both contemporaneous and lagged levels
      of achievement significantly predict initiation. In addition, change in academic
      achievement is an important predictor of initiation. That is, students who
      demonstrate a deterioration of their academic achievement over time are more
      likely to start using marijuana. Poor academic achievement and deterioration of
      academic achievement should be considered as risk factors for initiation of
      marijuana use among rural adolescents. Initiatives targeted at improving academic
      achievement and/or drug use prevention initiatives designed for poor achieving
      students may help to prevent initiation of marijuana use.

PMID- 16968871
TI  - Pharmacokinetic and demographic markers of 5-fluorouracil toxicity in 181
      patients on adjuvant therapy for colorectal cancer.
AB  - BACKGROUND: The relationship between 5-fluorouracil (5-FU) pharmacokinetics and
      toxicity following i.v. bolus administration has not been extensively studied.
      PATIENTS AND METHODS: One hundred and eighty-one patients on adjuvant therapy
      with 5-FU plus leucovorin for colorectal cancer were the study population. 5-FU
      pharmacokinetics was determined on day 2 of the first, third, and fifth cycles;
      type and the grade of adverse reactions were recorded on the next cycle. RESULTS:
      The 5-FU area under the curve (AUC) measured at the first cycle ranged between
      146 and 1236 mg x min/l and was significantly correlated with drug dose,
      patients' body weight (BW) and gender, females having higher AUCs. These
      covariates explained only 23% of AUC variability. AUC and age were the only
      covariates which discriminated between toxic (grade > or =2) and nontoxic cycles
      (grade <2), with an optimal AUC cut-off value of 596 mg x min/l. Such a
      correlation was lost during the next cycles following dose reduction because of
      toxicity in 80 patients. CONCLUSIONS: A method for calculating the initial 5-FU
      dose is proposed which takes into account patient BW, gender and a target AUC of
      596 mg x min/l. Nevertheless, it appears that a substantial part of 5-FU toxicity
      is not linked to pharmacokinetic factors and dose adjustments must still be on
      the basis of careful clinical surveillance.

PMID- 16968872
TI  - Sequential gemcitabine and cisplatin followed by docetaxel as first-line
      treatment of advanced urothelial carcinoma: a multicenter phase II study of the
      Hellenic Oncology Research Group.
AB  - BACKGROUND: The purpose of this study was to investigate the toxicity and
      efficacy of the sequential administration of gemcitabine (GMB) in combination
      with cisplatin (CDDP) followed by docetaxel (Taxotere) as first-line treatment of
      advanced urothelial carcinoma. PATIENTS AND METHODS: Patients [aged </=70 years
      and performance status (PS) (Eastern Cooperative Oncology Group) 0-2] with
      previously untreated locally advanced/recurrent or metastatic urothelial
      carcinoma were eligible. Study treatment consisted of GMB (1000 mg/m(2), days 1
      and 8) and CDDP (70 mg/m(2), day 1) (GP regimen), every 21 days for a total of
      four cycles followed by docetaxel (D; 100 mg/m(2), day 1) every 21 days for four
      cycles. RESULTS: Thirty-eight patients with a median age of 67 years were
      enrolled; 67% of them had PS 0 and 87% stage IV disease. Patients received a
      median of four GP and four D cycles per patient. Grade 3-4 neutropenia occurred
      in 27% and 63% patients with GP and D, respectively. Grade 3-4 thrombocytopenia
      occurred in 11% of patients, only with the GP regimen. Other toxic effects were
      mild. There was no toxic death. The objective response rate was 55.2% [95% CI:
      39.45%-71.07%]. Five patients had complete response (13.15%) and 16 patients had
      partial response (42.1%), while nine patients had disease stabilization (23.7%)
      (intention-to-treat analysis). After a median follow-up period of 13 months
      (range 1.5-40.5 months), the median time to progression was 6.8 months (range 1
      40.5 months), the median overall survival 13 months (range 1.5-40.5 months), and
      the 1-year survival rate 55.3%. CONCLUSION: The sequential administration of GP
      followed by D is active and well tolerated as first-line treatment of advanced
      urothelial carcinoma and merits to be further evaluated.

PMID- 16968873
TI  - Anemia may influence the outcome of patients undergoing neo-adjuvant treatment of
      rectal cancer.
AB  - BACKGROUND: We hypothesized that anemia could represent one of the major factors
      influencing the outcome of patients undergoing neo-adjuvant treatment of rectal
      cancer. PATIENTS AND METHODS: This analysis included all the consecutive patients
      who underwent neo-adjuvant treatment (chemotherapy and/or radiotherapy) before
      surgery for rectal cancer in three oncology/radiotherapy departments from June
      1996 to December 2003. RESULTS: Three hundred and seventeen patients were
      eligible for our analysis. Median age at diagnosis was 64 years (range 26-88
      years); male/female ratio was 184/133. Two hundred and eighty-five patients
      (89.9%) were diagnosed with adenocarcinoma, while 32/317 (10.1%) with mucinous
      adenocarcinoma. Neo-adjuvant treatments carried out were as follows: radiotherapy
      alone in 75/317 patients (23.7%), radiotherapy plus chemotherapy in 242/317
      patients (76.3%). At univariate and multivariate analysis, only the hemoglobin
      (Hb) level (group 1: < or=12 g/dl versus group 2: >12 g/dl) resulted in a
      significant factor for disease-free survival. The role of the Hb level seemed to
      be confirmed further by the clinical downstaging obtained in approximately 55% of
      patients in group 2, in comparison with 35% of the patients achieving a
      significant downstaging in group 1. CONCLUSION: Our results indicated that anemia
      could represent an important parameter able to influence the outcome in patients
      receiving neo-adjuvant treatment of rectal cancer.

PMID- 16968874
TI  - Evaluation of the prognostic and predictive value of p53 and Bcl-2 in breast
      cancer patients participating in a randomized study with dose-dense sequential
      adjuvant chemotherapy.
AB  - PURPOSE: To assess the prognostic and predictive significance of p53 and Bcl-2
      protein expression in high risk patients with breast cancer treated with dose
      dense sequential chemotherapy. PATIENTS AND METHODS: From June 1997 until
      November 2000, 595 patients were randomized to three cycles of epirubicin (E) 110
      mg/m2 followed by three cycles of paclitaxel (P) 250 mg/m2 followed by three
      cycles of 'intensified' CMF (cyclophosphamide 840 mg/m2, methotrexate 47 mg/m2
      and fluorouracil 840 mg/m2) or to four cycles of E, followed by four cycles of
      CMF. p53 and Bcl-2 expression was investigated by immunohistochemistry in 392 and
      397 patients respectively. RESULTS: Positive expression of p53 was detected in
      104 (26.5%) patients and was significantly associated with negative hormonal
      status, worse histologic grade, higher incidence of disease relapse and higher
      rate of death. p53 positive expression was a significant negative predictor of
      overall survival (OS) (P = 0.002) and disease-free survival (DFS) (P = 0.001).
      Negative expression of Bcl-2 was detected in 203 (51%) patients and was
      significantly associated with negative hormonal status. Multivariate analysis
      revealed that, positive p53 expression, higher number of positive nodes and worse
      tumor grade were related to significantly poorer OS and DFS. CONCLUSIONS: For
      both treatments, p53 positive expression was a significant negative prognostic
      factor for OS and DFS while Bcl-2 was not. No predictive ability of p53 status or
      Bcl-2 status for paclitaxel treatment was evident.

PMID- 16968875
TI  - Clinical relevance of melanoma micrometastases (<0.1 mm) in sentinel nodes: are
      these nodes to be considered negative?
AB  - As only about 20% of sentinel node (SN) positive melanoma patients have
      additional non-SN lymph node involvement in the Completion Lymph Node Dissection
      (CLND) specimen, we tried to identify a SN positive patient group, which can be
      spared CLND. Micro anatomic analyses of metastatic SNs were performed to identify
      patient/tumor and/or SN factors predicting additional non-SN positivity as well
      as disease-free and overall survival. SN positivity was found in 77 of 262 stage
      I/II patients, included into a prospective database (10/97-5/04). Of 74 patients
      pathology material was available for re-evaluation. Micro anatomic analyses
      categorized topography of SN-metastases, Starz classification and amount of SN
      tumor burden. Additional non-SN positivity, DFS, OS and was calculated for all
      analyses. Mean Breslow thickness was 3.5 mm (0.8-12.0); mean FU was 35 (6-81)
      months. There was no additional non-SN positivity for SN-micrometastases <0.1 mm.
      Topography of SN involvement had no impact on OS. Estimated 5-year OS rates for
      the different groups of <0.1 mm, 0.1-1.0 mm and >1.0 mm SN tumor burden were
      100%, 63% and 35% respectively. Distant metastases were exceedingly rare (1/16 =
      6.3%) in <0.1 mm SN-positive patients. On multivariate analysis the SN tumor
      burden was the most important prognostic factor for DFS (P = 0.005) and OS (P =
      0.03). Distant metastasis-free survival was identical (91%) to the 5-yr OS of SN
      negative patients, the estimated 5-yr OS was 100% for these patients and
      additional non-SN positivity was not observed. Therefore, our data suggest that
      patients with sub-micrometastases (<0.1 mm) in the SN may be judged as SN
      negative, as non-stage III, and are highly unlikely to benefit from CLND, which
      we no longer recommend.

PMID- 16968876
TI  - Is a patient's self-reported health-related quality of life a prognostic factor
      for survival in non-small-cell lung cancer patients? A multivariate analysis of
      prognostic factors of EORTC study 08975.
AB  - BACKGROUND: The aim of this prognostic factor analysis was to investigate if a
      patient's self-reported health-related quality of life (HRQOL) provided
      independent prognostic information for survival in non-small cell lung cancer
      (NSCLC) patients. PATIENTS AND METHODS: Pretreatment HRQOL was measured in 391
      advanced NSCLC patients using the EORTC QLQ-C30 and the EORTC Lung Cancer module
      (QLQ-LC13). The Cox proportional hazards regression model was used for both
      univariate and multivariate analyses of survival. In addition, a bootstrap
      validation technique was used to assess the stability of the outcomes. RESULTS:
      The final multivariate Cox regression model retained four parameters as
      independent prognostic factors for survival: male gender with a hazard ratio (HR)
      = 1.32 (95% CI 1.03-1.69; P = 0.03); performance status (0 to 1 versus 2) with HR
      = 1.63 (95% CI 1.04-2.54; P = 0.032); patient's self-reported score of pain with
      HR= 1.11 (95% CI 1.07-1.16; P < 0.001) and dysphagia with HR = 1.12 (95% CI 1.04
      1.21; P = 0.003). A 10-point shift worse in the scale measuring pain and
      dysphagia translated into an 11% and 12% increased in the likelihood of death
      respectively. A risk group categorization was also developed. CONCLUSION: The
      results suggest that patients' self-reported HRQOL provide independent prognostic
      information for survival. This finding supports the collection of such data in
      routine clinical practice.

PMID- 16968877
TI  - Effect of girdling above the abscission zone of fruit on 'Bartlett' pear ripening
      on the tree.
AB  - Pear fruit usually soften and develop a melting texture when harvested at the
      mature green stage and ripened. The reason why the fruit does not fully ripen on
      the tree is unknown. To clarify this, our attention was directed to the
      continuous supply of assimilates and/or other substances into the fruit via
      phloem transport. To determine the effect of inhibiting phloem transport on fruit
      ripening on the tree, a girdling treatment was applied to the branch above the
      abscission zone of 'Bartlett' pear (Pyrus communis L.). Girdling significantly
      enhanced the ethylene production of fruit on day 12 compared with control fruit.
      Fruit softening was also stimulated by girdling. On day 8, flesh firmness was
      similar in treated fruit on the tree and in fruit off the tree, and was
      significantly lower than that of untreated fruit on the tree. The patterns of
      transcript accumulation for the ethylene biosynthetic [1-aminocyclopropane-1
      carboxylate (ACC) synthase (PcACS) and ACC oxidase (PcACO)] and polygalacturonase
      (PcPG1 and PcPG3) genes showed good correspondence with ethylene production and
      fruit softening, respectively. Thus, fruit ripening on the tree was stimulated
      via ethylene by girdling on the branch above the abscission zone of fruit to
      interrupt phloem transport. Assimilates and/or other substances in phloem sap may
      prevent fruit ripening on the tree.

PMID- 16968878
TI  - Effect of partial rootzone drying on the concentration of zeatin-type cytokinins
      in tomato (Solanum lycopersicum L.) xylem sap and leaves.
AB  - Decreased cytokinin (CK) export from roots in drying soil might provide a root-to
      shoot signal impacting on shoot physiology. Although several studies show that
      soil drying decreases the CK concentration of xylem sap collected from the roots,
      it is not known whether this alters xylem CK concentration ([CK(xyl)]) in the
      leaves and bulk leaf CK concentration. Tomato (Solanum lycopersicum L.) plants
      were grown with roots split between two soil columns. During experiments, water
      was applied to both columns (well-watered; WW) or one (partial rootzone drying;
      PRD) column. Irrigation of WW plants aimed to replace transpirational losses
      every day, while PRD plants received half this amount. Xylem sap was collected by
      pressurizing detached leaves using a Scholander pressure chamber, and zeatin-type
      CKs were immunoassayed using specific antibodies raised against zeatin riboside
      after separating their different forms (free zeatin, its riboside, and
      nucleotide) by thin-layer chromatography. PRD decreased the whole plant
      transpiration rate by 22% and leaf water potential by 0.08 MPa, and increased
      xylem abscisic acid (ABA) concentration 2.5-fold. Although PRD caused no
      detectable change in [CK(xyl)], it decreased the CK concentration of fully
      expanded leaves by 46%. That [CK(xyl)] was maintained and not increased while
      transpiration decreased suggests that loading of CK into the xylem was also
      decreased as the soil dried. That leaf CK concentration did not decline
      proportionally with CK delivery suggests that other mechanisms such as CK
      metabolism influence leaf CK status of PRD plants. The causes and consequences of
      decreased shoot CK status are discussed.

PMID- 16968879
TI  - Sethoxydim affects lipid synthesis and acetyl-CoA carboxylase activity in
      soybean.
AB  - With rare exceptions, dicot plastids have been reported to contain only a
      multisubunit (prokaryotic) form of acetyl-coA carboxylase (ACCase), the first
      committed step of lipid biosynthesis. The sensitivity of most monocots to
      cyclohexanediones (CHDs) such as sethoxydim, has been shown to be associated with
      the presence in their plastids of a multifunctional (eukaryotic) form of ACCase.
      Little is known about the effects of sethoxydim on lipid metabolism and ACCase
      activity in dicots. Here it is shown that foliar lipid biosynthesis is
      differentially affected by the herbicide treatment in two dicot species,
      Nicotiana sylvestris (wild tobacco) and Glycine max (soybean). In N. sylvestris,
      the total lipid content of neoformed leaves harvested 2 weeks after the
      sethoxydim treatment was unaffected by doses of up to 10(-3) M sethoxydim. In
      soybean, lipid content decreased by 45% when 10(-5) M sethoxydim was used, and
      this was associated with a 30% reduction in fatty acid synthesis activity. ACCase
      activity of soybean plastidial preparations was 60% reduced in the presence of
      sethoxydim, whereas that of N. sylvestris was unaffected. Finally, the presence
      of a biotinylated 220 kDa polypeptide, corresponding in size to multifunctional
      ACCase, was observed in soybean plastids. Possible relationships between
      sensitivity of plastidial soybean ACCase towards sethoxydim, plastidial protein
      content, and altered de novo lipid biosynthesis in herbicide-treated plants are
      discussed.

PMID- 16968880
TI  - Phosphorylation of SPICK2, an AKT2 channel homologue from Samanea motor cells.
AB  - SPICK2, a homologue of the weakly-inward-rectifying Shaker-like Arabidopsis K
      channel, AKT2, is a candidate K+-influx channel participating in light- and clock
      regulated leaf movements of the legume, Samanea saman. Light and the biological
      clock regulate the in situ K+-influx channel activity differentially in extensor
      and flexor halves of the pulvinus (the S. saman leaf motor organ), and also
      though differently-the transcript level of SPICK2 in the pulvinus. This disparity
      between the in situ channel activity versus its candidate transcript, along with
      the sequence analysis of SPICK2, suggest an in situ regulation of the activity of
      SPICK2, possibly by phosphorylation and/or by interaction with cAMP. Consistent
      with this (i) the activity of the voltage-dependent K+-selective fraction of the
      inward current in extensor and flexor cells was affected differentially in whole
      cell patch-clamp assays promoting phosphorylation (using the protein phosphatase
      inhibitor okadaic acid); (ii) several proteins in isolated plasma membrane
      enriched vesicles of the motor cells underwent phosphorylation without an added
      kinase in conditions similar to patch-clamp; and (iii) the SPICK2 protein was
      phosphorylated in vitro by the catalytic subunit of the broad-range cAMP
      dependent protein kinase. All of these results are consistent with the notion
      that SPICK2 is the K+-influx channel, and is regulated in vivo directly by
      phosphorylation.

PMID- 16968881
TI  - Functional conservation of MADS-box factors controlling floral organ identity in
      rice and Arabidopsis.
AB  - Studies on MADS-box genes in Arabidopsis and other higher eudicotyledonous
      flowering plants have shown that they are key regulators of flower development.
      Since Arabidopsis and monocotyledonous rice are distantly related plant species
      it is interesting to investigate whether the floral organ identity factors have
      been conserved in their functions, and if not, to understand the differences.
      Arabidopsis and rice are very suitable for these studies since they are both
      regarded as models for plant functional genomics. Both their genomes are
      sequenced and tools are available for the analysis of gene function. These
      developments have accelerated experiments and increased our knowledge on rice
      gene function. Therefore it is the right moment to perform a comparative analysis
      on MADS-box factors controlling floral organ identity as reported in this review.

PMID- 16968882
TI  - A fluoroorotic acid-resistant mutant of Arabidopsis defective in the uptake of
      uracil.
AB  - A fluoroorotic acid (FOA)-resistant mutant of Arabidopsis thaliana was isolated
      by screening M2 populations of ethyl methane sulphonate (EMS)-mutagenized
      Columbia seed. FOA resistance was due to a nuclear recessive gene, for1-1, which
      locates to a 519 kb region in chromosome 5. Assays of key regulatory enzymes in
      de novo pyrimidine synthesis (uridine monophosphate synthase) and salvage
      biochemistry (thymidine kinase) confirmed that FOA resistance in for1-1/for1-1
      plants was not due to altered enzymatic activities. Uptake studies using
      radiolabelled purines, pyrimidines, and [14C]FOA reveal that for1-1/for1-1 plants
      were specifically defective in the uptake of uracil or uracil-like bases. To
      confirm such specificity, genetic crosses show that FOR1 is a distinct locus from
      FUR1 which encodes a deoxyuridine nucleoside transporter. In addition, for1
      1/for1-1 plants were restored to FOA sensitivity by transformation with the
      Escherichia coli uracil transporter gene uraA driven by the cauliflower mosaic
      virus (CaMV) 35S promoter. Molecular mapping studies reveal that FOR1 does not
      correspond to loci belonging to any of the six known nucleobase transporter
      families identified in the Arabidopsis genome. Moreover, FOR1 does not appear to
      regulate the transcript levels of either uracil transporter-encoding loci
      At2g03590 or At2g03530. The above results strongly suggest that the for1-1 mutant
      allele affects a transport mechanism that is specific for the uptake of uracil.

PMID- 16968883
TI  - Additional freeze hardiness in wheat acquired by exposure to -3 degreesC is
      associated with extensive physiological, morphological, and molecular changes.
AB  - Cold-acclimated plants acquire an additional 3-5 degrees C increase in freezing
      tolerance when exposed to -3 degrees C for 12-18 h before a freezing test (LT50)
      is applied. The -3 degrees C treatment replicates soil freezing that can occur in
      the days or weeks leading to overwintering by freezing-tolerant plants. This
      additional freezing tolerance is called subzero acclimation (SZA) to
      differentiate it from cold acclimation (CA) that is acquired at above-freezing
      temperatures. Using wheat as a model, results have been obtained indicating that
      SZA is accompanied by changes in physiology, cellular structure, the
      transcriptome, and the proteome. Using a variety of assays, including DNA arrays,
      reverse transcription-polymerase chain reaction (RT-PCR), 2D gels with mass
      spectroscopic identification of proteins, and electron microscopy, changes were
      observed to occur as a consequence of SZA and the acquisition of added freezing
      tolerance. In contrast to CA, SZA induced the movement of intracellular water to
      the extracellular space. Many unknown and stress-related genes were upregulated
      by SZA including some with obvious roles in SZA. Many genes related to
      photosynthesis and plastids were downregulated. Changes resulting from SZA often
      appeared to be a loss of rather than an appearance of new proteins. From a
      cytological perspective, SZA resulted in alterations of organelle structure
      including the Golgi. The results indicate that the enhanced freezing tolerance of
      SZA is correlated with a wide diversity of changes, indicating that the
      additional freezing tolerance is the result of complex biological processes.

PMID- 16968884
TI  - Use of thermal and visible imagery for estimating crop water status of irrigated
      grapevine.
AB  - Achieving high quality wine grapes depends on the ability to maintain mild to
      moderate levels of water stress in the crop during the growing season. This study
      investigates the use of thermal imaging for monitoring water stress. Experiments
      were conducted on a wine-grape (Vitis vinifera cv. Merlot) vineyard in northern
      Israel. Irrigation treatments included mild, moderate, and severe stress. Thermal
      and visible (RGB) images of the crop were taken on four days at midday with a
      FLIR thermal imaging system and a digital camera, respectively, both mounted on a
      truck-crane 15 m above the canopy. Aluminium crosses were used to match visible
      and thermal images in post-processing and an artificial wet surface was used to
      estimate the reference wet temperature (T(wet)). Monitored crop parameters
      included stem water potential (Psi(stem)), leaf conductance (g(L)), and leaf area
      index (LAI). Meteorological parameters were measured at 2 m height. CWSI was
      highly correlated with g(L) and moderately correlated with Psi(stem). The CWSI
      g(L) relationship was very stable throughout the season, but for that of CWSI
      Psi(stem) both intercept and slope varied considerably. The latter presumably
      reflects the non-direct nature of the physiological relationship between CWSI and
      Psi(stem). The highest R(2) for the CWSI to g(L) relationship, 0.91 (n=12), was
      obtained when CWSI was computed using temperatures from the centre of the canopy,
      T(wet) from the artificial wet surface, and reference dry temperature from air
      temperature plus 5 degrees C. Using T(wet) calculated from the inverted Penman
      Monteith equation and estimated from an artificially wetted part of the canopy
      also yielded crop water-stress estimates highly correlated with g(L) (R(2)=0.89
      and 0.82, respectively), while a crop water-stress index using 'theoretical'
      reference temperatures computed from climate data showed significant deviations
      in the late season. Parameter variability and robustness of the different CWSI
      estimates are discussed. Future research should aim at developing thermal imaging
      into an irrigation scheduling tool applicable to different crops.

PMID- 16968885
TI  - Acclimation of Rubisco specificity factor to drought in tobacco: discrepancies
      between in vitro and in vivo estimations.
AB  - In studies about the photosynthesis response to environmental stresses, such as
      drought, the Rubisco specificity factor (tau) is assumed to be constant or
      derived indirectly from gas exchange measurements. However, an analysis of the
      acclimation of tau to drought using in vitro determinations is lacking. The aim
      of the present work was to analyse the acclimation of tau to different drought
      intensities in tobacco (Nicotiana tabacum L.). Potted tobacco plants were
      subjected to three different water regimes (100%, 40%, and 15% of field capacity)
      and new leaves were allowed to develop. When acclimated leaves were fully
      developed, they were sampled for gas exchange and chlorophyll fluorescence
      measurements, as well as for the in vitro analysis of Rubisco kinetic properties.
      Relative water content and gas exchange decreased with increasing water shortage.
      The apparent Rubisco specificity factor as estimated in vivo by gas exchange
      decreased with water stress. However, in vitro estimates of tau were identical
      among treatments, as were Rubisco specific initial activity and activation state.
      The reasons for the observed discrepancy between in vitro and in vivo estimates
      are profusely discussed. It is suggested that the Rubisco specificity factor does
      not acclimate to water stress in the short term (weeks or months) in tobacco, and
      the validity of the so-called Laisk gas exchange method to estimate tau under
      drought is questioned.

PMID- 16968886
TI  - Evidence for cortical dysfunction and widespread manganese accumulation in the
      nonhuman primate brain following chronic manganese exposure: a 1H-MRS and MRI
      study.
AB  - Exposure to high levels of manganese (Mn) is known to produce a complex
      neurological syndrome with psychiatric disturbances, cognitive impairment, and
      parkinsonian features. However, the neurobiological basis of chronic low-level Mn
      exposure is not well defined. We now provide evidence that exposure to levels of
      Mn that results in blood Mn concentrations in the upper range of environmental
      and occupational exposures and in certain medical conditions produces widespread
      Mn accumulation in the nonhuman primate brain as visualized by T1-weighted
      magnetic resonance imaging. Analysis of regional brain Mn distribution using a
      "pallidal index equivalent" indicates that this approach is not sensitive to
      changing levels of brain Mn measured in postmortem tissue. Evaluation of
      longitudinal 1H-magnetic resonance spectroscopy data revealed a significant
      decrease (p = 0.028) in the N-acetylaspartate (NAA)/creatine (Cr) ratio in the
      parietal cortex and a near significant decrease (p = 0.055) in frontal white
      matter (WM) at the end of the Mn exposure period relative to baseline. Choline/Cr
      or myo-Inositol/Cr ratios did not change at any time during Mn exposure. This
      indicates that the changes in the NAA/Cr ratio in the parietal cortex are not due
      to changes in Cr but in NAA levels. In summary, these findings suggest that
      during chronic Mn exposure a significant amount of the metal accumulates not only
      in the basal ganglia but also in WM and in cortical structures where it is likely
      to produce toxic effects. This is supported by a significantly decreased, in the
      parietal cortex, NAA/Cr ratio suggestive of ongoing neuronal degeneration or
      dysfunction.

PMID- 16968887
TI  - Influence of compensatory renal growth on susceptibility of primary cultures of
      renal cells to chemically induced injury.
AB  - Primary cultures of rat renal proximal tubular (PT) and distal tubular (DT) cells
      from control and uninephrectomized (NPX) Sprague-Dawley rats were established to
      study whether the altered toxicological responses identified in freshly isolated
      cells are maintained in culture. Previous work showed that primary cultures of PT
      cells from hypertrophied rat kidneys maintained their differentiated properties,
      as evidenced by their high respiratory rate, active transport function, transport
      and metabolism of glutathione, and their hypertrophic phenotype. In the present
      study, primary cultures of PT cells from NPX rat kidneys, but to a much lesser
      extent DT cells, were more susceptible to cellular injury induced by either
      mercuric chloride, KCN, or tert-butyl hydroperoxide (tBH), than corresponding
      cells from normal rat kidneys. Direct comparisons of cytotoxicity and lipid
      peroxidation induced by tBH in freshly isolated renal cells showed that the
      primary cultures of cells from NPX rat kidneys retained their altered
      susceptibility relative to cells from control rats. These results show that
      primary cultures of PT cells from NPX rats are more sensitive to cellular injury
      induced by three mechanistically distinct toxicants, demonstrating their
      usefulness in the study of the molecular and biochemical basis for the altered
      phenotype of compensatory renal growth. This is the first report validating the
      use of a mammalian renal cell culture model to study the toxicological effects of
      compensatory renal cellular hypertrophy.

PMID- 16968888
TI  - Evidence that calcineurin is required for the genesis of bone-resorbing
      osteoclasts.
AB  - Here, we demonstrate that the Ca(2+)/calmodulin-sensitive phosphatase calcineurin
      is a necessary downstream mediator for osteoclast differentiation. Using
      quantitative PCR, we detected the calcineurin isoforms Aalpha, Abeta, Agamma
      (catalytic), and B1 (regulatory) in osteoclast precursor RAW-C3 cells. We found
      that, although the expression of these isoforms remained relatively unchanged
      during osteoclast differentiation, there was a profound increase in the
      expression of their primary substrate for calcineurin, nuclear factor of
      activated T cells (NFAT)c1. For gain-of-function studies, we incubated osteoclast
      precursors for 10 min with a calcineurin fusion protein (TAT-calcineurin Aalpha);
      this resulted in its receptorless influx into >90% of the precursor cells. A
      marked increase in the expression of the osteoclast differentiation markers
      tartrate-resistant acid phosphatase (TRAP) and integrin beta(3) followed. In
      addition, the expression of NFATc1, as well as the alternative substrate for
      calcineurin, IkappaBalpha, was significantly enhanced. Likewise, transfection
      with constitutively active NFAT resulted in an increased expression of both TRAP
      and integrin beta(3). In parallel loss-of-function studies, transfection with
      dominant-negative NFAT not only inhibited osteoclast formation but also reversed
      the induction of NFATc1, TRAP, and integrin beta(3) by TAT-calcineurin Aalpha.
      The expression of these markers was also inhibited by calcineurin Aalpha U1 small
      nuclear RNA, which significantly reduced calcineurin Aalpha mRNA and protein
      expression. Consistent with these observations, we observed a reduction in
      osteoclastogenesis in calcineurin Aalpha(-/-) cells and in osteoclast precursors
      treated with the calcineurin inhibitors cyclosporin A and FK506. Together, the
      gain- and loss-of-function experiments establish that calcineurin Aalpha is
      necessary for osteoclast formation from its precursor and that this occurs via an
      NFATc1-dependent mechanism.

PMID- 16968889
TI  - Fetuin-A uptake in bovine vascular smooth muscle cells is calcium dependent and
      mediated by annexins.
AB  - Fetuin-A is a known inhibitor of vascular calcification in vitro. In arteries
      with calcification, there is increased immunostaining for fetuin-A. However,
      vascular smooth muscle cells (VSMC) do not synthesize fetuin-A, suggesting fetuin
      A may be endocytosed to exert its inhibitory effects. To examine the mechanism by
      which fetuin-A is taken up in bovine VSMC (BVSMC), we examined living cells by
      confocal microscopy and determined the uptake of Cy5-labeled fetuin-A. The
      results demonstrated that fetuin-A was taken up in BVSMC only in the presence of
      extracellular calcium, whereas phosphorus had no effect. Additional studies
      demonstrated the calcium-dependent uptake was specific for fetuin-A and only
      observed in BVSMC and osteoblasts, but not epithelial, endothelial, or adipose
      cells. The uptake was dose dependent, but could not be inhibited by excess
      unlabeled fetuin-A, suggesting a fluid phase rather than a receptor-mediated
      process. Fetuin-A also induced a sustained increase in intracellular calcium in
      BVSMC in the presence of extracellular calcium, whereas there was no increase in
      the absence of extracellular calcium. To further characterize the uptake, we
      utilized an inhibitor of annexin calcium channel activity, demonstrating
      inhibition of both fetuin-A uptake and intracellular calcium increase. Finally,
      we demonstrate that fetuin-A binds to annexin II at the cell membrane of BVSMC.
      In summary, our study demonstrates calcium- and annexin-dependent uptake of
      fetuin-A that leads to a sustained rise in intracellular calcium. This regulated
      uptake may be a mechanism by which fetuin-A inhibits VSMC calcification in the
      presence of excess calcium.

PMID- 16968890
TI  - Renal upregulation of HO-1 reduces albumin-driven MCP-1 production: implications
      for chronic kidney disease.
AB  - Proteinuria contributes to chronic kidney disease by stimulating renal tubular
      epithelial cells to produce cytokines such as monocyte chemoattractant protein-1
      (MCP-1). The present study determined whether cellular overexpression of heme
      oxygenase-1 (HO-1) can influence albumin-stimulated MCP-1 production. In response
      to bovine serum albumin, NRK-52E cells constitutively overexpressing HO-1 (HO-1
      OE cells) exhibit less induction of MCP-1 mRNA and less production of MCP-1
      protein compared with similarly treated, control NRK-52E cells (CON cells). In
      wild-type NRK-52E cells, and under these conditions, we demonstrate that the
      induction of MCP-1 is critically dependent on intact NF-kappaB binding sites in
      the MCP-1 promoter. In response to albumin, CON cells exhibit activation of NF
      kappaB, and this is reduced in HO-1 OE cells. Albumin also activates ERK1/2 and
      increases ERK activity, both of which are exaggerated in HO-1 OE cells. Studies
      with an inhibitor of MAPK/ERK kinase (U0126) demonstrate that the inhibitory
      effects of U0126 on MCP-1 production are attenuated in HO-1 OE cells. We conclude
      that HO-1 overexpression in the proximal tubule reduces MCP-1 production in
      response to albumin, and this occurs, at least in part, by inhibiting an ERK
      dependent, NF-kappaB-dependent pathway at a site that is distal to the activation
      of ERK. These findings suggest that the induction of HO-1 in the proximal tubule,
      as occurs in chronic kidney disease, may be a countervailing response that
      reduces albumin-stimulated production of cytokines such as MCP-1.

PMID- 16968891
TI  - p21 and mTERT are novel markers for determining different ischemic time periods
      in renal ischemia-reperfusion injury.
AB  - In many clinical settings, the duration of renal ischemia and therefore the
      outcome of acute renal failure cannot be determined adequately. Renal ischemia
      reperfusion injury is known to shorten telomeres and upregulate stress-induced
      genes, such as the cyclin-dependent kinase (CDK) inhibitor p21. So far, the
      expression and role of CDK inhibitors, as well as mouse telomerase reverse
      transcriptase (mTERT), has not been investigated in a model with variable lasting
      ischemic periods. Male C57Bl/6 mice were subjected to renal ischemia reperfusion
      injury by clamping both renal pedicles for 10, 20, 30, and 45 min, and the
      kidneys were allowed to be reperfused for 3, 24, and 48 h. Expression of
      different CDK inhibitors and mTERT was evaluated. Mice developed signs of acute
      renal failure linear to the duration of the ischemic period. Real-time PCR
      revealed that mTERT was only significantly upregulated in kidneys after short
      ischemic periods (20 min). In contrast, p21 was constantly upregulated in kidneys
      after long ischemic intervals (30 and 45 min), but not in kidneys, which were
      clamped for shorter periods. Mainly, tubular cells contributed to the observed
      increase in p21 expression. Targeting p21 via the selective p53 inhibitor
      pifithrin-alpha was able to prevent acute renal failure when administered
      immediately before ischemia. The expression of another CDK inhibitor, namely p16,
      was differentially regulated, depending on the time of reperfusion. Taken
      together, we detected mTERT and p21 as "indicator" genes for short and long
      ischemic intervals, respectively. These two proteins might also be possible new
      therapeutic targets in the treatment and prevention of acute renal failure.

PMID- 16968893
TI  - Regulation of the Arf tumor suppressor in Emicro-Myc transgenic mice:
      longitudinal study of Myc-induced lymphomagenesis.
AB  - Lymphomagenesis in Emu-Myc mice is opposed by the Arf tumor suppressor, whose
      inactivation compromises p53 function and accelerates disease. Finding nascent
      Emu-Myc-induced tumors in which p19Arf causes cell-cycle arrest or apoptosis is
      problematic, since such cells will be eliminated until Arf or p53 function is
      lost. Knock-in mice expressing a green fluorescent protein (GFP) in lieu of Arf
      coding sequences allow analysis of Arfpromoter regulation uncoupled from p19Arf
      action. Prior to frank lymphoma development, unexpectedly low levels of Emu-Myc
      induced p19Arf or GFP were expressed. However, as lymphomas arose in Arf+/GFP
      heterozygotes, additional oncogenic events synergized with Emu-Myc to further
      induce the functionally null Arf-Gfp allele. Concomitant up-regulation of p19Arf
      was not observed; instead, the wild-type allele was inactivated. We infer that
      very low levels of Arf are tumor suppressive, and that further induction provides
      the selective pressure for the emergence of tumors that have inactivated the
      gene.

PMID- 16968892
TI  - Spontaneously reduced blood pressure load in the rat streptozotocin-induced
      diabetes model: potential pathogenetic relevance.
AB  - The rat streptozotocin (STZ)-induced diabetes model is widely used to investigate
      the pathogenesis of diabetic nephropathy. However, overt nephropathy is
      inexplicably slow to develop in this model compared with renal mass reduction
      (RMR) models. To examine whether blood pressure (BP) differences correlated with
      the time course of glomerulosclerosis (GS), BP was measured continuously
      throughout the course by radiotelemetry in control (n = 17), partially insulin
      treated STZ-diabetes (average blood glucose 364 +/- 15 mg/dl; n = 15), and two
      normotensive RMR models (systolic BP <140 mmHg)--uninephrectomy (UNX; n = 16) and
      3/4 RMR by surgical excision [right nephrectomy + excision of both poles of left
      kidney (RK-NX); n = 12] in Sprague-Dawley rats. Proteinuria and GS were assessed
      at approximately 16-20 wk (all groups) and at 36-40 wk (all groups except RK-NX).
      At 16 wk, significantly greater proteinuria and GS had developed in the RK-NX
      group compared with the other three groups (not different from each other). By 36
      40 wk, substantial proteinuria and GS had also developed in the UNX group, but
      both the control and the STZ-diabetic rats exhibited comparable modest
      proteinuria and minimal GS. Systolic BP (mmHg) was significantly reduced in the
      STZ-diabetic rats (116 +/- 1.1) compared with both control (124 +/- 1.0) and RMR
      (128 +/- 1.2 and 130 +/- 3.0) groups (P < 0.01). Similarly, "BP load" as
      estimated by BP power spectral analysis was also lower in the STZ-diabetic rats.
      Given the known protective effects of BP reductions on the progression of
      diabetic nephropathy, it is likely that this spontaneous reduction in ambient BP
      contributes to the slow development of GS in the STZ-diabetes model compared with
      the normotensive RMR models.

PMID- 16968894
TI  - Monoclonal immunoglobulin with antitransferrin activity: A rare cause of
      hypersideremia with increased transferrin saturation.
AB  - Two unusual but similar cases of very high serum iron, extremely high transferrin
      concentrations (5.4 to 6.5 g/L), and increased transferrin saturation are
      reported. No anemia or microcytosis was observed. The ferritin concentration
      remained within the normal range, and no iron overload was observed. In one case,
      the in vivo half-life of 59Fe-labeled transferrin was shown to be prolonged (206
      minutes versus 75 minutes for controls). In both patients, a monoclonal IgG was
      observed in the serum. The association between serum transferrin and monoclonal
      IgG was demonstrated by Western blot analysis and affinity chromatography. We
      suggest that the transferrin bound to the monoclonal IgG molecule has a prolonged
      half-life in the circulation, leading to high transferrin concentrations, and
      that the increased serum iron values prevent the onset of anemia. The
      antitransferrin activity of monoclonal antibody should be added to the list of
      situations accounting for elevated serum iron with elevated transferrin
      saturation.

PMID- 16968895
TI  - Relationship of expression of aquaglyceroporin 9 with arsenic uptake and
      sensitivity in leukemia cells.
AB  - Arsenic trioxide (As2O3) is highly efficacious in acute promyelocytic leukemia
      (APL). Aquaglyceroporin 9 (AQP9) is a transmembrane protein that may be involved
      in arsenic uptake. In 10 of 11 myeloid and lymphoid leukemia lines, quantitative
      polymerase chain reaction (Q-PCR) and Western blotting showed that AQP9
      expression correlated positively with As2O3-induced cytotoxicity. As a proof-of
      principle, transfection of EGFP-tagged AQP9 to the hepatoma line Hep3B, not
      expressing AQP9 and As2O3 insensitive, led to membrane AQP9 expression and
      increased As2O3-induced cytotoxicity. Similarly, the chronic myeloid leukemia
      line K562 expressed low levels of AQP9 and was As2O3 insensitive. The K562(EGFP
      AQP9) transfectant accumulated significantly higher levels of intracellular
      arsenic than control K562(EGFP) when incubated with As2O3, resulting in
      significantly increased As2O3-induced cytotoxicity. Pretreatment of the myeloid
      leukemia line HL-60 with all-trans retinoic acid (ATRA) up-regulated AQP9,
      leading to a significantly increased arsenic uptake and As2O3-induced
      cytotoxicity on incubation with As2O3, which might explain the synergism between
      ATRA and As2O3. Therefore, AQP9 controlled arsenic transport and might determine
      As2O3 sensitivity. Q-PCR showed that primary APL cells expressed AQP9
      significantly (2-3 logs) higher than other acute myeloid leukemias (AMLs), which
      might explain their exquisite As2O3 sensitivity. However, APL and AML with
      maturation expressed comparable AQP9 levels, suggesting that AQP9 expression was
      related to granulocytic maturation.

PMID- 16968896
TI  - Differentiation of CD1a- and CD1a+ monocyte-derived dendritic cells is biased by
      lipid environment and PPARgamma.
AB  - Accumulating data have shown that the microenvironment of dendritic cells
      modulates subtype differentiation and CD1 expression, but the mechanisms by which
      exogenous factors confer these effects are poorly understood. Here we describe
      the dependence of CD1a- monocyte-derived dendritic cell (moDC) development on
      lipids associated with the expression of peroxisome proliferator-activated
      receptor-gamma (PPARgamma). We also show the consecutive differentiation of
      immature CD1a-PPARgamma+ moDCs to CD1a+PPARgamma- cells limited by serum
      lipoproteins and terminated by proinflammatory cytokines. Immature CD1a- moDCs
      possess higher internalizing capacity than CD1a+ cells, whereas both activated
      subtypes have similar migratory potential but differ in their cytokine and
      chemokine profiles, which translates to distinct T-lymphocyte-polarizing
      capacities. CD1a+ moDCs stand out by their capability to secrete high amounts of
      IL-12p70 and CCL1. As lipoproteins skew moDC differentiation toward the
      generation of CD1a-PPARgamma+ cells and inhibit the development of CD1a+PPARgamma
      cells, we suggest that the uptake of lipids results in endogenous PPARgamma
      agonists that induce a cascade of gene transcription coordinating lipid
      metabolism, the expression of lipid-presenting CD1 molecules, subtype dichotomy,
      and function. The presence of CD1a-PPARgamma+ and CD1a+PPARgamma- DCs in lymph
      nodes and in pulmonary Langerhans cell histiocytosis confirms the functional
      relevance of these DC subsets in vivo.

PMID- 16968897
TI  - Foamy-virus-mediated gene transfer to canine repopulating cells.
AB  - Foamy virus (FV) vectors are particularly attractive gene-transfer vectors for
      stem-cell gene therapy because they form a stable transduction intermediate in
      quiescent cells and can efficiently transduce hematopoietic stem cells. Here, we
      studied the use of FV vectors to transduce long-term hematopoietic repopulating
      cells in the dog, a clinically relevant large animal model. Mobilized canine
      peripheral blood (PB) CD34+ cells were transduced with an enhanced green
      fluorescent protein (EGFP)-expressing FV vector in an 18-hour transduction
      protocol. All 3 dogs studied had rapid neutrophil engraftment to greater than
      500/microL with a median of 10 days. Transgene expression was detected in all
      cell lineages (B cells, T cells, granulocytes, red blood cells, and platelets),
      indicating multilineage engraftment of transduced cells. Up to 19% of blood cells
      were EGFP+, and this was confirmed at the DNA level by real-time polymerase chain
      reaction (PCR) and Southern blot analysis. These transduction rates were higher
      than the best results we obtained previously with lentiviral vectors in a similar
      transduction protocol. Integration site analysis also demonstrated polyclonal
      repopulation and the transduction of multipotential hematopoietic repopulating
      cells. These data suggest that FV vectors should be useful for stem-cell gene
      therapy, particularly for applications in which short transduction protocols are
      critical.

PMID- 16968898
TI  - Discoidin domain receptor 1 contributes to eosinophil survival in an NF-kappaB
      dependent manner in Churg-Strauss syndrome.
AB  - Churg-Strauss syndrome (CSS) is a systemic disease that shows marked eosinophilia
      along with eosinophil infiltration in the tissue. Prolonged eosinophil survival
      plays an important role in the pathogenesis of CSS; however, its detailed
      molecular mechanism remains unclear. Discoidin domain receptor 1 (DDR1) is a
      receptor tyrosine kinase, and its ligand is collagen. DDR1 was expressed in human
      leukocytes and fibroblasts, and it plays an important role in leukocyte cytokine
      production and fibroblast survival in an NF-kappaB-dependent manner. In this
      study, we examined in vitro and in vivo eosinophil DDR1 expression and its
      function in CSS patients. The expression level of DDR1 was significantly higher
      in the eosinophils of CSS patients, and the predominant isoform was DDR1b.
      Immunohistochemical findings revealed that the tissue-infiltrating eosinophils
      expressed endogenous DDR1. In CSS patients, DDR1 activation inhibited Fas
      agonistic antibody-induced apoptosis and up-regulated Fas agonistic antibody
      induced cytokine production of eosinophils in an NF-kappaB-dependent manner.
      Suppression of DDR1 expression in the eosinophils by using RNA interference and
      addition of the DDR1-blocking protein abolished these effects. We propose that
      DDR1 contributes to the eosinophil survival in the tissue microenvironment of CSS
      and that it might be involved in the development of CSS.

PMID- 16968899
TI  - Efficiency of T-cell receptor expression in dual-specific T cells is controlled
      by the intrinsic qualities of the TCR chains within the TCR-CD3 complex.
AB  - Genetic engineering of T lymphocytes is an attractive strategy to specifically
      redirect T-cell immunity toward viral infections and malignancies. We previously
      demonstrated redirected antileukemic reactivity of cytomegalovirus (CMV)-specific
      T cells by transfer of minor histocompatibility antigen HA-2-specific T-cell
      receptors (TCRs). HA-2-TCR-transferred CMV-specific T cells were potent effectors
      against HA-2-expressing leukemic cells, as well as CMV-expressing cells.
      Functional activity of these T cells correlated with TCR cell-surface expression.
      In the present study we analyzed which properties of transferred and endogenous
      TCRs are crucial for efficient cell-surface expression. We demonstrate that
      expression of the introduced TCR is not a random process but is determined by
      characteristics of both the introduced and the endogenously expressed TCR. The
      efficiency of TCR cell-surface expression is controlled by the intrinsic quality
      of the TCR complex. In addition, we demonstrate that chimeric TCRs can be formed
      and that efficiency of TCR expression is independent of whether TCRs are
      retrovirally introduced or naturally expressed. In conclusion, introduced,
      endogenous, and chimeric TCRs compete for cell-surface expression in favor of the
      TCR-CD3 complex with best-pairing properties.

PMID- 16968900
TI  - Oncogenic role of Pax5 in the T-lymphoid lineage upon ectopic expression from the
      immunoglobulin heavy-chain locus.
AB  - Four of 9 PAX transcription factor genes have been associated with chromosomal
      translocations in human tumors, although their oncogenic potential has not yet
      been demonstrated in transgenic mouse models. The B-lymphoidPAX5 gene
      participates in the generation of the t(9;14)(p13;q32) translocation in germinal
      center B cells, which leads to deregulated PAX5 expression under the control of
      the immunoglobulin heavy-chain (IgH) locus in a subset of B-cell non-Hodgkin
      lymphomas. Here we reconstructed a human t(9;14) translocation in a knock-in
      mouse by inserting a PAX5 minigene into the IgH locus. The IgH(P5ki) allele,
      which corresponds to a germline rather than somatic mutation, is activated in
      multipotent hematopoietic progenitors and is subsequently expressed in dendritic
      cells (DCs) and in natural killer (NK), T, and B cells. Ectopic Pax5 expression
      interferes with normal T-cell development and causes immature T-lymphoblastic
      lymphomas in IgH(P5ki/+) and IgH(P5ki/P5ki) mice. Aggressive T-cell lymphomas
      develop even faster in Ik(Pax5/+) mice expressing Pax5 from the Ikaros locus.
      Pax5 expression in thymocytes activates B-cell-specific genes and represses T
      lymphoid genes, suggesting that Pax5 contributes to lymphomagenesis by
      deregulating the T-cell gene-expression program. These data identify Pax5 as a
      potent oncogene and demonstrate that the T-lymphoid lineage is particularly
      sensitive to the oncogenic action of Pax5.

PMID- 16968901
TI  - Regulation of epsilon germline transcription and switch region mutations by IgH
      locus 3' enhancers in transgenic mice.
AB  - Germline (GL) transcription is regulated by specific promoters and immunoglobulin
      heavy chain (IgH) 3' locus enhancers and is necessary for Ig class-switch
      recombination (CSR). We have generated different transgenic lines containing the
      GL epsilon promoter, switch (S) epsilon region, and constant (C) epsilon region
      with or without the DNase I-sensitive regions (HS) 3A-HS1,2 or HS3B-HS4 3' IgH
      enhancer pairs. The enhancerless construct was expressed in B cells activated by
      interleukin (IL)-4 and CD40, thus resembling regulation of the endogenous gene.
      Both enhancer-containing transgenes efficiently increased expression in B cells
      and were strongly up-regulated by stimuli. In addition, Sepsilon regions of the
      transgene containing HS3B-HS4 were mutated in activated, sorted B cells. Such
      mutations are known to precede CSR and are dependent on activation-induced
      cytidine deaminase (AID). Our findings show that all elements necessary for
      recruitment of the recombination machinery are present in the transgene
      containing HS3 and HS4. These enhancers probably provide something more specific
      than mere increased accessibility of switch regions. We propose that
      transcription factors binding the enhancers help to target the recombination
      machinery to the switch regions.

PMID- 16968906
TI  - Unraveling the dynamic transcriptome.

PMID- 16968907
TI  - A discussion of statistical methods for design and analysis of microarray
      experiments for plant scientists.

PMID- 16968902
TI  - IL-15 and dermal fibroblasts induce proliferation of natural regulatory T cells
      isolated from human skin.
AB  - Regulatory T cells (Tregs) are crucial for the induction and maintenance of self
      tolerance and are present in peripheral tissues such as skin and gut under
      normal, noninflamed conditions. We report isolation and expansion of the Treg
      population resident in normal human skin. Cutaneous Tregs expressed high levels
      of CD25, L-selectin, GITR, FOXP3, and intracellular CTLA-4, low levels of CD69,
      and high levels of the skin-homing addressins CLA, CCR4, and CCR6. Skin Tregs
      suppressed the proliferation of CD25(lo) T cells from the same skin sample in
      response to CD3 and CD28 antibodies. Suppression was dependent on cell contact
      and not affected by neutralizing antibodies to interleukin-10 (IL-10) and
      transforming growth factor-beta (TGF-beta). Surprisingly, cutaneous Tregs
      proliferated in an antigen-independent manner when cultured in contact with
      dermal fibroblasts and IL-15, conditions similar to those found in chronically
      inflamed skin. We hypothesize that local proliferation of Tregs may occur within
      inflamed skin and could serve as a brake for cutaneous inflammation as well as a
      mechanism for the homeostatic proliferation of natural Tregs that has been
      observed within intact organisms.

PMID- 16968908
TI  - Cotrimoxazole prophylaxis and malaria in Africa: Have the important questions
      been answered?

PMID- 16968910
TI  - Polymorphisms in pfcrt, pfmdr1, dhfr genes and in vitro responses to
      antimalarials in Plasmodium falciparum isolates from Bangui, Central African
      Republic.
AB  - Drug resistance is probably the greatest challenge to most malaria-control
      programs. Given the limited resources for other malarial-control measures,
      rational drug used is crucial. Molecular markers for parasite resistance such as
      pfcrt, pfmdr-1, and dhfr have the potential to be used in an integrated fashion
      to provide timely information that is useful to policy makers. Therefore, we
      evaluated polymorphisms in these genes from Plasmodium falciparum and their
      association with in vitro antimalarial drug resistance to 135 parasites samples
      collected in Bangui in 2004. For the dhfr gene, we found a strong association
      between the dhfr genotype and chemosensitivity to pyrimethamine. For the pfcrt
      gene, we found that haplotypes with mutant-type alleles led to significant
      changes in the IC50 values for chloroquine, monodesethylamodiaquine, and quinine.
      We found no correlations for the pfmdr1 gene. These findings suggest that a
      regular monitoring and screening for resistance markers for antifolates and for
      chloroquine could act as an adjunct to in vivo trials.

PMID- 16968909
TI  - Effect of cotrimoxazole prophylaxis taken by human immunodeficiency virus (HIV)
      infected persons on the selection of sulfadoxine-pyrimethamine-resistant malaria
      parasites among HIV-uninfected household members.
AB  - The purpose of this prospective cohort study was to assess the effect of
      cotrimoxazole prophylaxis taken by human immunodeficiency virus (HIV)-infected
      persons on the selection of sulfadoxine-pyrimethamine (SP)-resistant malaria
      parasites among HIV-uninfected household members. A total of 2,567 HIV-uninfected
      persons from 605 households were followed and blood specimens were collected each
      time an episode of Plasmodium falciparum malaria was diagnosed. Study
      participants were living in households where HIV-infected persons were either
      taking (exposed) or not taking (unexposed) cotrimoxazole prophylaxis. From all
      malaria episodes diagnosed, 50% of the specimens were randomly selected and
      tested for the presence of five key mutations known to mediate resistance to SP
      (dihydrofolate reductase [dhfr] Asn-108, Ile-51, and Arg-59, and dihydropteroate
      synthase [dhps] Gly-437 and Glu-540). Plasmodium falciparum isolates were
      recovered from 163 specimens in the exposed households and 113 specimens in the
      unexposed households, with similar proportions containing the dhfr triple mutant
      (37% versus 45%; P = 0.18), the dhps double mutant (64% versus 62%; P = 0.81),
      and the dhfr/dhps quintuple mutant (30% versus 32%; P = 0.74). The HIV-uninfected
      persons living with HIV-infected household members taking cotrimoxazole
      prophylaxis had a lower incidence of malaria (incidence rate ratio [IRR] = 0.64,
      95% confidence interval [CI] = 0.50-0.83, P = 0.001) and fewer malaria episodes
      due to parasites containing the dhfr/dhps quintuple mutant (IRR = 0.61, 95% CI =
      0.41-0.91, P = 0.014). Cotrimoxazole prophylaxis taken by HIV-infected persons
      did not select for SP-resistant malaria parasites among HIV-uninfected household
      members, and was associated with a lower overall incidence of SP-resistant
      malaria among household members.

PMID- 16968911
TI  - Molecular epidemiology of malaria in Cameroon. XXI. Baseline therapeutic efficacy
      of chloroquine, amodiaquine, and sulfadoxine-pyrimethamine monotherapies in
      children before national drug policy change.
AB  - The availability of epidemiologic data on drug-resistant malaria based on a
      standardized clinical and parasitological protocol is a prerequisite for a
      rational therapeutic strategy to control malaria. As part of the surveillance
      program on the therapeutic efficacy of the first-line (chloroquine and
      amodiaquine) and second-line (sulfadoxine-pyrimethamine) drugs for the management
      of uncomplicated Plasmodium falciparum infections, non-randomized studies were
      conducted in symptomatic children aged less than 10 years according to the World
      Health Organization protocol (14-day follow-up period) at 12 sentinel sites in
      Cameroon between 1999 and 2004. Of 1,407 children enrolled in the studies, 460,
      444, and 503 were treated with chloroquine, amodiaquine, or sulfadoxine
      pyrimethamine, respectively. Chloroquine treatment resulted in high failure rates
      (proportion of early and late failures, 48.6%). Amodiaquine was effective at all
      study sites (proportion of failures, 7.3%). Sulfadoxine-pyrimethamine therapy was
      less effective than amodiaquine (P < 0.05), with failures observed in 9.9% of
      patients. Chloroquine is no longer a viable option and has been withdrawn from
      the official drug outlets in Cameroon. Amodiaquine and, to a lesser extent,
      sulfadoxine-pyrimethamine monotherapies are still effective in Cameroon, but
      further development of resistance to these drugs should be delayed by the novel
      strategy using artemisinin-based combination therapy. Our findings indicate that
      amodiaquine is the most rational partner for artesunate. Studies on the efficacy
      of artesunate-amodiaquine combination are currently being undertaken at several
      sites in the country.

PMID- 16968912
TI  - Molecular epidemiology of malaria in Cameroon. XXII. Geographic mapping and
      distribution of Plasmodium falciparum dihydrofolate reductase (dhfr) mutant
      alleles.
AB  - Sulfadoxine-pyrimethamine (SP) is still a useful drug to combat chloroquine
      resistant Plasmodium falciparum malaria in Cameroon. Because of several
      disadvantages of the in vivo test and in vitro drug sensitivity assays, molecular
      assays are an alternative laboratory tool to monitor the evolution of antifolate
      resistance, especially over the entire country that is characterized by several
      epidemiologic strata and malaria transmission patterns. In this study, 1,430
      blood samples from either symptomatic children or asymptomatic carriers were
      collected from 14 sites throughout the country between 1999 and 2003 for the
      analysis of dihydrofolate reductase (dhfr) sequence. Of 1,368 samples (95.7%)
      that were successfully amplified, 1,180 were analyzed by direct sequencing of the
      polymerase chain reaction product, and 188 were analyzed by restriction enzymes.
      The prevalences of the wild-type, single Asn-108 mutation, double Arg-59/Asn-108
      mutations, double Ile-51/Asn-108 mutations, triple Ile-51/Arg-59/Asn-108
      mutations, and mixed alleles were 20.8%, 2.8%, 5.7%, 0.8%, 62.2%, and 7.6%,
      respectively. The proportions of triple dhfr mutations were > 60% at all study
      sites, with the exception of the eastern province (42% triple mutants in Bertoua
      in 1999) and the northern provinces (11-35% triple mutants in Ngaoundere, Garoua,
      and Maroua). In these two provinces, the proportion of mutant parasites increased
      significantly (P < 0.05) over the period of 2-4 years. Furthermore, there was a
      higher proportion (P < 0.05) of wild-type parasites in the northern provinces,
      compared with the rest of the country. The geographic mapping of molecular
      markers offers a novel tool for monitoring the epidemiology of drug-resistant
      malaria.

PMID- 16968913
TI  - Primaquine: report from CDC expert meeting on malaria chemoprophylaxis I.
AB  - Primaquine phosphate has been used for preventing relapse of Plasmodium vivax and
      P. ovale malaria since the early 1950s, based on its ability to kill latent
      (hypnozoite) and developing liver stages of these parasites. There are three uses
      for primaquine in malaria: radical cure of established infection with P. vivax or
      P. ovale malaria; presumptive anti-relapse therapy (PART; terminal prophylaxis)
      in persons with extensive exposure to these parasites; and primary prophylaxis
      against all malaria species. All persons for whom primaquine is being considered
      must have a glucose-6-phosphate dehydrogenase (G6PD) enzyme level checked before
      use, and persons who have a deficiency of G6PD must not take primaquine for
      prophylaxis or PART. The recommended adult dose for PART based on clinical trials
      and expert opinion is 30 mg base daily for 14 days, started on return from a
      malarious region and overlapping with a blood schizonticide. The adult dose for
      primary prophylaxis is 30 mg daily begun 1 day before travel and continued for 7
      days after return. This review will examine the evidence for these
      recommendations.

PMID- 16968914
TI  - Cost considerations of malaria chemoprophylaxis including use of primaquine for
      primary or terminal chemoprophylaxis.
AB  - The costs of mefloquine, chloroquine, doxycycline, primaquine, and
      atovaquone/proguanil are calculated for various durations of exposure to malaria.
      The cost is included for detecting glucose 6-phosphate dehydrogenase (G6PD)
      deficiency before administering primaquine for primary or terminal prophylaxis.
      For durations of exposure ranging from 3 to 730 days, if no terminal prophylaxis
      is given, doxycycline (generic) is the least expensive regimen. Compared with
      doxycycline hyclate, chloroquine costs three to four times more, and primaquine,
      after screening for G6PD, costs about eight times more. Atovaquone/proguanil is
      less expensive than mefloquine for a 3-day exposure, but more expensive for 7 or
      more days. When terminal chemoprophylaxis with primaquine for 14 days is used in
      addition to doxycycline, mefloquine, chloroquine, or atovaquone/proguanil,
      primaquine alone is the least expensive regimen for exposures of < 10 days.
      Thereafter, doxycycline plus 14 days of primaquine is most economical. For
      subsequent exposures when G6PD status is already known, primaquine alone is the
      least expensive regimen for up to 9 days of exposure, but doxycycline is less
      expensive thereafter. In general, generic doxycycline hyclate is the least
      expensive regimen. Primaquine alone is economically attractive. Mefloquine,
      doxycyline monohydrate, and atovaquone/proguanil, the most expensive regimens,
      are similar in cost for a 7-day exposure, but thereafter, atovaquone/proguanil is
      much more expensive.

PMID- 16968915
TI  - Socio-economic differences in preferences and willingness to pay for different
      providers of malaria treatment in southeast Nigeria.
AB  - This article determined whether there are links between socio-economic status
      (SES) and preferences of consumers for different strategies for improving timely
      and appropriate management of malaria. Ranking of preferences and willingness to
      pay (WTP) for 5 different strategies for improving the management of malaria in
      Enugu State, southeast Nigeria were elicited from randomly selected respondents.
      The results showed that the people were also willing to pay for improved
      management of malaria, though the levels of WTP was dependent on the SES of the
      respondents, with the poorest SES group willing to pay the least amount of money.
      Also, the respondents generally mostly preferred timely and appropriate
      management of malaria through formal public healthcare system. Hence, to decrease
      the inequity in malaria management and ensure the ready availability of
      appropriate treatment to the poorest households, the government should increase
      the availability and accessibility of publicly owned healthcare services,
      complemented by community-based health services.

PMID- 16968916
TI  - Randomized, double-blind, placebo-controlled study of Malarone for malaria
      prophylaxis in non-immune Colombian soldiers.
AB  - Malarone was compared with placebo in a double-blind, randomized, placebo
      controlled trial of prophylaxis of malaria in predominately Plasmodium vivax
      areas of Colombia. The study population consisted of 180 completely non-immune
      Colombian soldiers, male, average age 19 years, and average weight 63 kg. Twenty
      four subjects were considered unevaluable because of compliance issues, including
      one Malarone subject (with no detectable drug levels) who became infected with P.
      vivax. Of the 97 evaluable subjects who received Malarone (250 mg atovaquone plus
      100 mg proguanil hydrochloride) daily from 1 day before entering the endemic area
      to 7 days after leaving the endemic area, none became parasitemic. Of the 46
      evaluable placebo subjects, 11 became infected with P. vivax and 2 became
      infected with Plasmodium falciparum. The protective efficacy of Malarone for all
      malaria and for P. vivax malaria was 100% (LL 95% CI = 63%) and 100% (LL 95% CI =
      58%), respectively, and was 96% if the one case with undetectable blood levels
      was included. Malarone has high protective efficacy for P. vivax in Colombia.

PMID- 16968917
TI  - Thrombocytopenia in falciparum malaria is associated with high concentrations of
      IL-10.
AB  - Over the last decade, a number of observations have suggested that platelets may
      play a role in the pathophysiology of severe malaria. However, somewhat
      paradoxically, thrombocytopenia is not associated clearly with outcome. We
      studied the relationship between thrombocytopenia and cytokines in Kenyan
      children with severe malaria and showed that thrombocytopenia (platelet count <
      150 x 10(9)/L) strongly correlates with high levels of interleukin (IL)-10.
      Several studies have shown that high levels of IL-10 are associated with a
      favorable outcome in severe malaria. Taken together, these data suggest why
      thrombocytopenia has a complex relationship with severe disease and suggest one
      mechanism whereby IL-10 may modify the outcome of severe disease.

PMID- 16968918
TI  - Critical evaluation of different methods for measuring the functional activity of
      antibodies against malaria blood stage antigens.
AB  - Antibodies are thought to be the primary immune effectors in the defense against
      erythrocytic stage Plasmodium falciparum. Thus, malaria vaccines directed to
      blood stages of infection are evaluated based on their ability to induce
      antibodies with anti-parasite activity. Such antibodies may have different
      effector functions (e.g., inhibition of invasion or inhibition of parasite
      growth/development) depending on the target antigen. We evaluated four methods
      with regards to their ability to differentiate between invasion and/or growth
      inhibitory activities of antibodies specific for two distinct blood stage
      antigens: AMA1 and MSP1(42). We conclude that antibodies induced by these vaccine
      candidates have different modes of action that vary not only by the antigen, but
      also by the strain of parasite being tested. Analysis based on parasitemia and
      viability was essential for defining the full range of anti-parasite activities
      in immune sera.

PMID- 16968919
TI  - Simplified multi-organ dysfunction score predicts disability in African children
      with Plasmodium falciparum malaria.
AB  - In this prospective study, we assessed the simplified multi-organ dysfunction
      score (sMODS) in 485 consecutive African children, hospitalized with Plasmodium
      falciparum malaria. Children were grouped according to their ability to walk
      unaided (Group 1, N = 414), sit unaided (Group 2, N = 63), or inability of both
      (Group 3, N = 8) before contracting malaria. The sMODS on admission to hospital
      was highly correlated with prolonged disease duration in Groups 1 and 2 (Spearman
      r = 0.79 and r = 0.78, respectively). A sMODS of > or = 16 was indicative for
      prolonged disease duration in Group 1 (> 48 hours of inability to walk,
      sensitivity of 87%, specificity of 82%) and Group 2 (> 24 hours of inability to
      sit, sensitivity of 100%, and specificity of 78%.). The simplified MODS is a
      simple and sensitive measure merit of severity of illness in children with P.
      falciparum malaria and allows early prognostic evaluation.

PMID- 16968920
TI  - Malaria vector productivity in relation to the highland environment in Kenya.
AB  - The reasons for the resurgence of malaria in the African highlands have been
      subject of debate. Because vector abundance is important for malaria
      transmission, gaining a better understanding of vector biology is a key to
      understanding the mechanisms of highland malaria. We studied vector productivity
      in relation to the highland environment and compared productivity between lowland
      and highland sites. We found lower vector productivity in the highland and in
      wetlands where the temperature was lower. Immature stage development time was
      significantly longer in the highland site. Development time was significantly
      shorter in aquatic habitats in cultivated areas than in wetlands, and survival
      rate was significantly higher in cultivated areas. Fecundity was significantly
      lower in the highland site. These findings suggest that changes in local
      temperature and land use contribute to an increase of malaria vectors in the
      highland.

PMID- 16968921
TI  - Identification of all members of the anopheles culicifacies complex using allele
      specific polymerase chain reaction assays.
AB  - Anopheles culicifacies, a complex of five isomorphic sibling species, is a major
      vector of malaria in India and neighboring countries. The five species are
      provisionally designated as species A, B, C, D, and E. Polytene chromosome
      examination has been the only method available that differentiates four members
      of this complex in areas where species E is not prevalent. However, this
      technique requires the mosquitoes to be in the half-gravid stage and thus limits
      its application to only about one fourth to one third of the total adult
      collection and excludes immature stages completely. For species E, both polytene
      chromosome examination and mitotic chromosome examination of F1 males are
      required. A polymerase chain reaction (PCR) assay based on the D3 domain (D3-PCR)
      of 28S rDNA and a polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) assay involving ITS2 of rDNA are available for the
      discrimination of the members of the An. culicifacies complex. However, both
      these can only differentiate species A and D from species B, C, and E. We report
      here two allele-specific PCR assays (AD-PCR and BCE-PCR) using sequence
      differences in the mitochondrial cytochrome oxidase II (CO II) subunit. The AD
      PCR assay distinguishes species A and D, whereas the BCE-PCR assay distinguishes
      species B, C, and E. Thus, with a combination of two PCR assays, namely the D3
      PCR/ITS2-RsaI assay, followed by either the AD-PCR or the BCE-PCR assay, it is
      possible to identify individual specimens of any of the species of this complex.
      This assay system is the first, and the best available at present to distinguish
      all sibling species and especially to discriminate non-vector, species B from all
      the vector species, A, C, D, and E, of the An. culicifacies complex. Until
      another DNA-based method involving fewer steps is developed, this assay system
      can be used in all malaria epidemiologic studies where An. culicifacies is
      prevalent.

PMID- 16968922
TI  - Genetic relationships among Mayaro and Una viruses suggest distinct patterns of
      transmission.
AB  - Mayaro and Una viruses (MAYV, UNAV) are mosquito-borne alphaviruses that may
      cause an acute febrile illness characterized by headache, retro-orbital pain, and
      rash that may progress to a severe and prolonged arthralgia. MAYV was first
      isolated in Trinidad in 1954, and UNAV was first identified in northern Brazil in
      1959. Since then, numerous isolates of these agents have been made from humans,
      wild vertebrates, and mosquitoes in several countries in northern South America.
      Serological evidence suggests that these viruses are also present in portions of
      Central America. Because little is known about the natural transmission cycle of
      MAYV and virtually nothing is known about UNAV transmission, 63 isolates covering
      the known geographic and temporal ranges were used in phylogenetic analyses to
      aid in understanding the molecular epidemiology. Approximately 2 kb from the E1
      and E2 glycoprotein genes and the complete 3' non-coding region were sequenced.
      Phylogenetic analyses of these sequences indicated that two distinct genotypes of
      MAYV exist with a distinct clade consisting exclusively of UNAV (previously
      designated as a subtype of MAYV). One MAYV genotype (genotype D) contains
      isolates from Trinidad and the northcentral portion of South America including
      Peru, French Guiana, Surinam, Brazil, and Bolivia. All of these isolates are
      highly conserved with a nucleotide divergence of < 6%. The second MAYV genotype
      (genotype L) contains isolates only from Brazil that are highly conserved (< 4%
      nucleotide divergence) but are quite distinct (15-19%) from the first genotype
      isolates. These analyses provide possible explanations for the natural ecology
      and transmission of MAYV and UNAV.

PMID- 16968923
TI  - Clinical features of 62 imported cases of dengue fever in Japan.
AB  - To describe the clinical features of dengue cases in Japan, a retrospective study
      was conducted on 62 laboratory-confirmed Japanese dengue cases presented to Tokyo
      Metropolitan Komagome Hospital between 1985 and 2000. Age distribution was from
      18 to 62 years old (mean, 31.5 years). All cases were imported from abroad and
      diagnosed as dengue fever. Clinical manifestations included fever (100%),
      headache (90%), and skin rash (82%). Laboratory examinations revealed
      leukocytopenia (71%), thrombocytopenia (57%), elevated levels of serum aspartate
      aminotransferase (78%), and lactate dehydrogenase (71%). Antibody responses were
      consistent with that of secondary flavivirus infection in 60% of cases. Severity
      of symptoms in patients with primary dengue antibody response and those with
      secondary flavivirus antibody responses didn't show statistical significance.
      Dengue virus infection should be taken into consideration in the differential
      diagnosis of febrile patients who recently entered Japan from tropical or
      subtropical countries.

PMID- 16968924
TI  - HDV genotypes in the Western Brazilian Amazon region: A preliminary report.
AB  - In Brazil, hepatitis delta virus (HDV) is only reported in Western Amazonia,
      where severe cases of acute and chronic HDV hepatitis have been described. The
      study area was chosen in the States of Acre and Rondonia where most cases of
      hepatitis B virus (HBV)/HDV are reported. From December 2003 to October 2004, 40
      HBsAg carriers with anti-HDV IgM were selected. An epidemiologic questionnaire,
      including demographic and clinical/epidemiologic variables was filled out. HDV
      amplification and genotyping were performed. Genotype I was detected in 22
      patients (55.0%), whereas genotype III was identified in 18 (45.0%). Patients who
      were infected with genotype I were older (45.1 +/- 17.8 years) than patients
      infected with genotype III (32.8 +/- 10.9 years; P = 0.01). No symptoms were
      reported by 21 (52.5%) patients. Otherwise, 19 (47.5%) had symptoms (fatigue,
      abdominal pain, weight loss, and decompensated liver disease) that motivated them
      to seek medical care. Genotype III carriers were more symptomatic, but no
      statistical significance was achieved. Our preliminary results show that HDV
      genotypes I and III are present in Brazilian Amazonia and that HDV genotype III
      is not limited to the Amerindian population.

PMID- 16968925
TI  - Previous infection with West Nile or St. Louis encephalitis viruses provides
      cross protection during reinfection in house finches.
AB  - House finches are competent hosts for both West Nile and St. Louis encephalitis
      viruses and frequently become infected during outbreaks. In the current study,
      House finches were infected initially with either West Nile or St. Louis
      encephalitis viruses and then challenged 6 weeks post infection with either
      homologous or heterologous viruses. Although mortality rates were high during
      initial infection with West Nile virus, prior infection with either virus
      prevented mortality upon challenge with West Nile virus. Prior infection with
      West Nile virus provided sterilizing immunity against both viruses, whereas prior
      infection with St. Louis encephalitis virus prevented viremia from St. Louis
      encephalitis virus, but only reduced West Nile virus viremia titers. Immunologic
      responses were measured by enzyme immunoassay and plaque reduction neutralization
      tests. Heterologous challenge with West Nile virus in birds previously infected
      with St. Louis encephalitis virus produced the greatest immunologic response,
      markedly boosting antibody levels against St. Louis encephalitis virus. Our data
      have broad implications for free-ranging avian serological diagnostics and
      possibly for the recent disappearance of St. Louis encephalitis virus from
      California.

PMID- 16968926
TI  - Short report: Isolation of two vaccinia virus strains from a single bovine
      vaccinia outbreak in rural area from Brazil: Implications on the emergence of
      zoonotic orthopoxviruses.
AB  - Outbreaks of bovine vaccinia disease caused by circulation of Vaccinia virus
      (VACV) strains have been a common occurrence in Brazil in the recent years, being
      an important emergent zoonosis. During a single outbreak that took place in 2001,
      two genetically different VACV strains were isolated and named Guarani P1 virus
      (GP1V) and Guarani P2 virus (GP2V). Molecular diagnosis was done through
      restriction fragment length polymorphism (RFLP) of ati gene (A26L) and by
      sequence analysis of a group of five VACV genes including the C11R, J2R, A56R,
      B18R, and E3L genes. These findings confirmed the co-circulation of two different
      Vaccinia virus strains during the same outbreak, raising important questions
      about the origin, emergence, and circulation of VACV strains in Brazil.

PMID- 16968927
TI  - A new genetic variant of La Crosse virus (bunyaviridae) isolated from New
      England.
AB  - La Crosse virus (LACV) is found primarily in the Midwestern and Appalachian
      regions of the United States where it is a leading cause of mosquito-borne
      encephalitis in children. To determine whether the distribution of this virus
      extends further east into New England, we analyzed a bunyavirus that was isolated
      from a pool of eastern tree-hole mosquitoes, Ochlerotatus triseriatus (= Aedes
      triseriatus), collected from Fairfield, Connecticut (CT) in 2005. Nucleotide and
      encoded amino acid sequences from portions of the S, M, and L segments were more
      similar to the prototype strain of La Crosse virus than that of closely related
      snowshoe hare virus. Phylogenetic analysis of sequences from the M segment
      indicated that the CT isolate represents a distinct lineage of La Crosse virus,
      diverging earliest from other strains found in southeastern, central, and
      northeastern United States. Despite low sequence homology with other viral
      strains, the CT isolate was antigenically similar to the prototype strain of LACV
      by plaque-reduction neutralization tests with polyclonal and monoclonal
      antibodies. This represents the first isolation of LACV in New England to our
      knowledge and suggests long-term independent evolution of the CT isolate.

PMID- 16968928
TI  - Polymerase chain reaction detection and serologic follow-up after treatment with
      benznidazole in Bolivian children infected with a natural mixture of Trypanosoma
      cruzi I and II.
AB  - Thirty-five Bolivian children (5-10 years of age) seropositive for infection with
      T. cruzi underwent specific chemotherapy with benznidazole. Before treatment,
      57.1% had a positive parasitologic diagnosis. Some patients presented an early
      conversion by polymerase chain reaction of blood samples, while others were still
      positive four and seven months after the end of the treatment, which indicated an
      absence of parasite clearance. Strain typing showed that most patients were
      infected by a mixture of clones I and II of T. cruzi. Serologic conversion in
      conventional tests and antibodies to shed acute-phase antigen were observed in
      two and four patients, respectively. For the other patients, the average rate of
      antibody decay was half the initial rate. The parasitologic and serologic data
      indicated that chemotherapy acts throughout the course of infection in a long
      lasting process in which the decrease of specific antibody production is related
      to the reduction of the live parasite load.

PMID- 16968929
TI  - Short report: ITS-1 DNA sequence confirmation of Leishmania major as a cause of
      cutaneous leishmaniasis from an outbreak focus in the Ho district, southeastern
      Ghana.

PMID- 16968930
TI  - Knowledge, attitude, and practices related to Kala-azar in a rural area of Bihar
      state, India.
AB  - The Indian Government aspires to eliminate Kala-azar by 2010. Success of any
      disease control program depends on community participation, and there is no
      published data about the knowledge, attitude, and practices of the community
      about Kala-azar in endemic regions of India. For this knowledge, attitude, and
      practices (KAP) study, the heads of 3,968 households in a rural area, consisting
      of 26,444 populations, were interviewed using a pre-tested, semi-structured
      schedule. Most of the study subjects (97.4%) were aware of Kala-azar. Fever
      (71.3%) and weight loss (30.5%) were the most commonly known symptoms. The
      infectious nature of the disease was known to 39.9%. The majority believed that
      the disease spreads by mosquito bites (72.8%). For 63.6%, the breeding site of
      the vector was garbage collection. Only 23.6% preferred the public health sector
      for treatment, and 55.9% believed that facilities at primary health centers are
      not adequate. Poor knowledge of the study subjects about the disease and breeding
      sites of the vector underscores the need for health educational campaigns if the
      elimination program is to succeed.

PMID- 16968931
TI  - Helicobacter pylori infection in children of low and high socioeconomic status in
      northeastern Brazil.
AB  - This survey was designed to evaluate the prevalence of Helicobacter pylori
      infection in asymptomatic children from families of low and high socioeconomic
      status living in two neighboring communities in Teresina in northeastern Brazil.
      The study included 303 children, 163 (53.8%) males and 140 (46.2%) females,
      ranging in age from 6 months to 12 years. Helicobacter pylori status was
      determined by the H. pylori stool antigens test, in which sensitivity and
      specificity values for Brazilian children were 96.9% and 100%, respectively. The
      prevalence rates were 55.0% (93 of 169) and 16.4% (22 of 134) for children of low
      and high socioeconomic status, respectively (P < 0.001). Infection with H. pylori
      occurred early in life (before 2 years of age) in both groups (22.9% versus
      14.3%; P = 0.061) and increased as the children became older. The rate of
      infection in children 11-12 years of age living in the poor area was as high as
      the levels found in Brazilian adults. An improved standard of living is followed
      by a sharp decrease in the prevalence rates in children, even in a developing
      country such as Brazil.

PMID- 16968932
TI  - Enteropathogenic Escherichia coli o157 in Bangui and N'Goila, Central African
      Republic: A brief report.
AB  - Escherichia coli O157:H7 producing Shiga like toxins is a food-borne pathogen
      frequently isolated in Bangui from patients with hemorrhagic colitis (HC). This
      survey provides comprehensive data on the high prevalence of E. coli O157:H7
      infection in Bangui: carriage of E. coli O157:H7 by zebu (Bos indicus) and fish,
      contamination of the fields at N'Goila where the butchers kill the zebus, and
      contamination of the field surface water along the M'Poko River upstream of the
      Oubangui River where fish are caught, appear to be important contributory
      factors. We also describe novel strains of serogroup O157:NM isolated from zebu
      and from fish; a variety of assays indicate that these strains belong to the
      enteropathogenic pathotype, though they lack certain genetic elements thought to
      be diagnostic for this pathotype.

PMID- 16968933
TI  - A simple fluorogenic method to detect Vibrio cholerae and Aeromonas hydrophila in
      well water for areas impacted by catastrophic disasters.
AB  - The colony overlay procedure for peptidases (COPP) is a simple, fluorogenic assay
      that can rapidly detect and quantify Vibrio cholerae and Aeromonas hydrophila in
      well water. Cleavage of the substrate L-lysyl-7-amino-4-trifluoromethylcoumarin
      by enzymes present in Vibrio and Aeromonas species produces fluorescent foci on
      cellulose acetate membranes exposed to long-wave ultraviolet light. Vibrio
      cholerae O1, O139, O155, and A. hydrophila were readily detected using this
      procedure, whereas Enterobacteriaceae and other non-Vibrionaceae pathogens did
      not produce fluorescence. The assay is practical for assessing the relative
      safety of well water in areas that have experienced catastrophic devastation from
      natural disasters, acts of war, or civil strife and may help curb outbreaks of
      cholera and other enteric illnesses in affected areas. In tropical climates, the
      procedure may be adapted for use in areas without electricity.

PMID- 16968934
TI  - Prevalence of HIV and syphilis in pregnant women in Leon, Nicaragua.
AB  - The objective of this study was to determine the prevalence of HIV and syphilis
      and to identify risk factors among pregnant women visiting antenatal clinics in
      Leon, Nicaragua. During February to April 2004, blood samples from pregnant women
      were collected after written consent had been obtained. The samples were tested
      for antibodies against HIV and Treponema pallidum. A questionnaire was also
      completed. In total, 1,059 women were included. Antibodies against HIV were not
      detected in any of the women, whereas antibodies against T. pallidum were
      detected in 16 (1.5%). Risk factors for syphilis included illiteracy, lower
      education, and two or more pregnancies. HIV does not seem to be highly prevalent
      among pregnant women in Leon (prevalence, 0%; 95% CI, 0.0-0.3). The higher
      proportion of women infected with syphilis than found in earlier studies suggests
      that sexually transmitted diseases are circulating in the general population and
      highlights the increasing importance of HIV prevention.

PMID- 16968935
TI  - Laboratory use in Ghana: physician perception and practice.
AB  - Clinical diagnosis of infectious diseases in Africa has been associated with
      increased misdiagnosis and mortality, but when laboratory testing is available,
      it remains underused. We retrospectively compared infectious diagnoses, test
      results, anti-microbial use, and patient cost with laboratory and physician
      surveys at a teaching hospital in Ghana to evaluate the potential barriers to
      laboratory use and financial impact for patients. Laboratory capacity was high,
      but physician survey results and objective data indicated a reliance on clinical
      judgment and empirical therapy. For the study period, 9-15% of malaria diagnoses,
      34-43% of urinary tract infections (UTIs), and 62% of meningitis cases were
      supported by abnormal laboratory results. For the same period, 0.82-2.09 units of
      antibiotics were consumed per patient day, and patient cost for antibiotics was
      4.8-21.6 times that of laboratory testing. Physician perception regarding the
      value of diagnostic testing is potentially a major barrier to laboratory use,
      resulting in empiricism, disproportionate anti-microbial administration, and cost
      to patients.

PMID- 16968936
TI  - Salivary gland extracts of Culicoides sonorensis inhibit murine lymphocyte
      proliferation and no production by macrophages.
AB  - Culicoides biting midges serve as vectors of pathogens affecting humans and
      domestic animals. Culicoides sonorensis is a vector of several arboviruses in
      North American that cause substantial economic losses to the US livestock
      industry. Previous studies showed that C. sonorensis saliva, like the saliva of
      many hematophagous arthropods, contains numerous pharmacological agents that
      affect hemostasis and early events in the inflammatory response, which may
      enhance the infectivity of Culicoides-borne pathogens. This paper reports on the
      immunomodulatory properties of C. sonorensis salivary gland extracts on murine
      immune cells and discusses the possible immunomodulatory role of C. sonorensis
      saliva in vesicular stomatitis virus infection of vertebrate hosts. Splenocytes
      treated with C. sonorensis mitogens were significantly affected in their
      proliferative response, and peritoneal macrophages secreted significantly less
      NO. A 66-kDa glycoprotein was purified from C. sonorensis salivary gland extract,
      which may be in part responsible for these observations and may be considered as
      a vaccine candidate.

PMID- 16968937
TI  - Rocky mountain spotted fever hospitalizations among American Indians.
AB  - To describe the epidemiology of Rocky Mountain spotted fever (RMSF) among
      American Indians/Alaska Natives (AI/ANs), we conducted a retrospective analysis
      of hospitalization records with an RMSF diagnosis using Indian Health Service
      (IHS) hospital discharge data for calendar years 1980-2003. A total of 261 RMSF
      hospitalizations were reported among AIs, for an average annual hospitalization
      rate of 1.21 per 100,000 persons; two deaths were reported (0.8%). Most
      hospitalizations (88.5%) occurred in the Southern Plains region, where the rate
      was 4.23 per 100,000 persons. Children 1-4 years of age had the highest age
      specific hospitalization rate of 2.50 per 100,000 persons. The overall annual
      RMSF hospitalization rate declined during the study period. Understanding the
      epidemiology of RMSF among AI/ANs and educating IHS/tribal physicians on the
      diagnosis of tick-borne diseases remain important for the prompt treatment of
      RMSF and the reduction of the disease occurrence among AI/ANs, particularly in
      high-risk areas.

PMID- 16968938
TI  - Usefulness of nested PCR for the diagnosis of scrub typhus in clinical practice:
      A prospective study.
AB  - The aims of this study were to determine the diagnostic accuracy and clinical
      usefulness of using nested polymerase chain reaction (PCR) for the diagnosis of
      scrub typhus through a prospective comparison of nested PCR and indirect
      immunofluorescent antibody assay (IFA). We conducted a multi-center prospective
      study of patients who were suffering with possible scrub typhus infection. Whole
      blood samples were collected for PCR testing, and sera were obtained for serology
      evaluation using the indirect IFA and the passive hemagglutination assay (PHA).
      We prospectively studied 135 patients with possible scrub typhus. One hundred
      eighteen patients were confirmed as having scrub typhus, 7 patients were
      undetermined, and 10 patients were confirmed as having other diseases. The
      results of nested PCR assay showed a sensitivity of 82.2% and a specificity of
      100%. Ninety-six of the 118 patients were positive for IgM on their admission
      day. Of the 22 patients who were negative for IgM antibody at admission, 19 had
      positive results for nested PCR of the buffy coat. The nested PCR assay of the
      buffy coat is useful as a rapid and reliable test for confirming the diagnosis of
      scrub typhus.

PMID- 16968939
TI  - Outbreak of cyclosporiasis at a naval base in Lima, Peru.
AB  - Cyclospora cayetanensis is emerging as an important cause of food-borne diarrheal
      outbreaks, especially in developed regions like the United States and Europe. We
      describe an outbreak of cyclosporiasis in Peruvian naval recruits that we believe
      to be the first among a local population in a developing region.

PMID- 16968940
TI  - A growing degree-days based time-series analysis for prediction of Schistosoma
      japonicum transmission in Jiangsu province, China.
AB  - It has been suggested that global warming may alter the frequency and
      transmission dynamics of vector-borne diseases. To test this claim for
      schistosomiasis, we conducted a time-series analysis from 1972-2002 for 39 of the
      70 counties of Jiangsu province, eastern China, where Schistosoma japonicum is
      partially endemic. We used a modeling approach to estimate the annual growing
      degree-days (AGDD), employing a lower temperature threshold of 15.3 degrees C.
      Our final model included both temporal and spatial components, the former
      consisting of second order polynomials in time plus a seasonality component,
      whereas the spatial trend was formed by second order polynomials of the
      coordinates plus the thin-plate smoothing splines. We found that temperature
      increased over the past 30 years in all observing stations. There were distinct
      temporal trends with seasonality and periodicities of 12, 6, and 3 months,
      whereas only marginal spatial variation was observed. The predicted AGDDs for
      2006 and 2003 showed increases for the entire Jiangsu province, with the AGDDs
      difference between these two time points exhibiting an increase from north to
      south. Our data suggest that changes in temperature will alter the extent and
      level of schistosomiasis transmission, which is relevant for the control of S.
      japonicum in a future warmer China.

PMID- 16968941
TI  - Chinese herbal medicine Yin-Chen-Extract as an adjunct to anthelmintic
      albendazole used against Angiostrongylus cantonensis-induced eosinophilic
      meningitis or meningoencephalitis.
AB  - The effects of albendazole and Yin-Chen-Extract co-therapy on Angiostrongylus
      cantonensis-induced eosinophilic meningitis in BALB/c mice were evaluated. Assay
      indicators for the therapeutic effect include worm recovery, histopathological
      score of the fourth ventricle, tissue-type plasminogen activator, urokinase-type
      plasminogen activator, matrix metalloproteinase-9, cerebrospinal fluid total
      protein, leukocyte counts, and proinflammatory cytokines. As a result,
      albendazole and Yin-Chen-Extract co-therapy significantly decreased (P < 0.05)
      these factors. Although Yin-Chen-Extract may possess pharmacologic activities
      beneficial to the inhibition of parasite-induced inflammation, many of these
      hypothetical benefits await scientific testing and confirmation before
      application. This study suggests that the combination of Yin-Chen-Extract and
      albendazole has synergistic effects in managing eosinophilic meningitis or
      eosinophilic meningoencephalitis.

PMID- 16968942
TI  - A modified filter paper culture technique for screening of Strongyloides
      stercoralis ivermectin sensitivity in clinical specimens.
AB  - An in vitro test for the detection of ivermectin sensitivity of Strongyloides
      stercoralis in human clinical specimens was developed. The test has a simple
      procedure that combines parasite culture with a drug assay. It is based on the
      principle of the drug effect on larval development test, combined with a modified
      coproculture using the filter paper culture technique. This does not require
      parasite isolation, and drug sensitivity can be shown in relationship to the
      dose. This test can be applied in field surveys for anthelmintic sensitivity and
      for appropriate drug rotation strategies when drug resistance occurs.

PMID- 16968943
TI  - Prevalence and species distribution of E. Histolytica and E. Dispar in the Venda
      region, Limpopo, South Africa.
AB  - The prevalence and species distribution of Entamoeba histolytica and E. dispar in
      the Venda region were determined in stool samples collected from public hospitals
      and primary schools by ELISA and a nested polymerase chain reaction (PCR). E.
      histolytica was detected in 37/197 (18.8%) and 1/47 (2.1%) samples, whereas
      50/197 (25.3%) and 4/47 (8.5%) had E. dispar in the hospitals and schools,
      respectively. The age groups most infected were 0-2 (33%) years followed by 20-29
      years (27%). E. histolytica was significantly associated with diarrhea (77.4%
      versus 22.6%; chi 2 = 39.48, P < 0.05), and with the presence of lactoferrin
      (85.7% versus 14.2%) in the stools, indicating intestinal inflammation (chi 2 =
      29.605, P < 0.05). E. histolytica was found in 5 (16.12%) of the 31 HIV-positive
      individuals and in 33 (15.5%) of the 213 HIV-negative individuals. E. histolytica
      infections are common in the Venda region and are associated with diarrhea and
      intestinal inflammation.

PMID- 16968945
TI  - Functionally defective high-density lipoprotein: a new therapeutic target at the
      crossroads of dyslipidemia, inflammation, and atherosclerosis.
AB  - High-density lipoproteins (HDL) possess key atheroprotective biological
      properties, including cellular cholesterol efflux capacity, and anti-oxidative
      and anti-inflammatory activities. Plasma HDL particles are highly heterogeneous
      in physicochemical properties, metabolism, and biological activity. Within the
      circulating HDL particle population, small, dense HDL particles display elevated
      cellular cholesterol efflux capacity, afford potent protection of atherogenic low
      density lipoprotein against oxidative stress and attenuate inflammation. The
      antiatherogenic properties of HDL can, however be compromised in metabolic
      diseases associated with accelerated atherosclerosis. Indeed, metabolic syndrome
      and type 2 diabetes are characterized not only by elevated cardiovascular risk
      and by low HDL-cholesterol (HDL-C) levels but also by defective HDL function.
      Functional HDL deficiency is intimately associated with alterations in
      intravascular HDL metabolism and structure. Indeed, formation of HDL particles
      with attenuated antiatherogenic activity is mechanistically related to core lipid
      enrichment in triglycerides and cholesteryl ester depletion, altered
      apolipoprotein A-I (apoA-I) conformation, replacement of apoA-I by serum amyloid
      A, and covalent modification of HDL protein components by oxidation and
      glycation. Deficient HDL function and subnormal HDL-C levels may act
      synergistically to accelerate atherosclerosis in metabolic disease. Therapeutic
      normalization of attenuated antiatherogenic HDL function in terms of both
      particle number and quality of HDL particles is the target of innovative
      pharmacological approaches to HDL raising, including inhibition of cholesteryl
      ester transfer protein, enhanced lipidation of apoA-I with nicotinic acid and
      infusion of reconstituted HDL or apoA-I mimetics. A preferential increase in
      circulating concentrations of HDL particles possessing normalized antiatherogenic
      activity is therefore a promising therapeutic strategy for the treatment of
      common metabolic diseases featuring dyslipidemia, inflammation, and premature
      atherosclerosis.

PMID- 16968946
TI  - Eicosanoid transcellular biosynthesis: from cell-cell interactions to in vivo
      tissue responses.
AB  - The biosynthesis of the biologically active metabolites of arachidonic acid
      involves a number of enzymes that are differentially expressed in cells.
      Prostaglandins and thromboxanes are derived from the chemically unstable
      prostaglandin (PG) H(2) intermediate synthesized by PGH synthases (cyclooxygenase
      1/2) and leukotrienes from chemically unstable leukotriene A(4) by 5
      lipoxygenase. Additional enzymes transform these reactive intermediates to a
      variety of chemical structures known collectively as the lipid mediators.
      Although some cells have the complete cassette of enzymes required for the
      production of biologically active prostaglandins and leukotrienes, the actual
      biosynthetic events often are a result of cell-cell interaction and a transfer of
      these chemically reactive intermediates, PGH(2) and leukotriene A(4), between
      cells. This process has come to be known as transcellular biosynthesis of
      eicosanoids and requires a donor cell to synthesize and release one component of
      the biosynthetic cascade and a second, accessory cell to take up that
      intermediate and process each into the final biologically active product. This
      review focuses on the evidence for transcellular biosynthetic events for
      prostaglandins, leukotrienes, and lipoxins occurring during cell-cell
      interactions. Evidence for arachidonic acid serving as a transcellular
      biosynthetic intermediate is presented. Experiments for transcellular events
      taking place in vivo that reveal the true complexity of eicosanoid biosynthesis
      within tissues are also reviewed.

PMID- 16968944
TI  - International Union of Pharmacology LVIII: update on the P2Y G protein-coupled
      nucleotide receptors: from molecular mechanisms and pathophysiology to therapy.
AB  - There have been many advances in our knowledge about different aspects of P2Y
      receptor signaling since the last review published by our International Union of
      Pharmacology subcommittee. More receptor subtypes have been cloned and
      characterized and most orphan receptors de-orphanized, so that it is now possible
      to provide a basis for a future subdivision of P2Y receptor subtypes. More is
      known about the functional elements of the P2Y receptor molecules and the
      signaling pathways involved, including interactions with ion channels. There have
      been substantial developments in the design of selective agonists and antagonists
      to some of the P2Y receptor subtypes. There are new findings about the mechanisms
      underlying nucleotide release and ectoenzymatic nucleotide breakdown.
      Interactions between P2Y receptors and receptors to other signaling molecules
      have been explored as well as P2Y-mediated control of gene transcription. The
      distribution and roles of P2Y receptor subtypes in many different cell types are
      better understood and P2Y receptor-related compounds are being explored for
      therapeutic purposes. These and other advances are discussed in the present
      review.

PMID- 16968948
TI  - The lipoxin receptor ALX: potent ligand-specific and stereoselective actions in
      vivo.
AB  - Lipoxins (LXs) and aspirin-triggered LX (ATL) are trihydroxytetraene-containing
      eicosanoids generated from arachidonic acid that are distinct in structure,
      formation, and function from the many other proinflammatory lipid-derived
      mediators. These endogenous eicosanoids have now emerged as founding members of
      the first class of lipid/chemical mediators involved in the resolution of the
      inflammatory response. Lipoxin A(4) (LXA(4)), ATL, and their metabolic stable
      analogs elicit cellular responses and regulate leukocyte trafficking in vivo by
      activating the specific receptor, ALX. ALX was the first receptor cloned and
      identified as a G protein-coupled receptor (GPCR) for lipoxygenase-derived
      eicosanoids with demonstrated cell type-specific signaling pathways. ALX at the
      level of DNA has sequence homology to the N-formylpeptide receptor and as an
      orphan GPCR was initially referred to as the N-formylpeptide receptor-like 1.
      Although LXA(4) is the endogenous potent ligand for ALX activation, a number of
      peptides can also activate this receptor to stimulate calcium mobilization and
      chemotaxis in vitro. In contrast with LXA(4), the counterparts of many of these
      peptides in vivo remain to be established. The purpose of this review is to
      highlight the molecular characterization of the ALX receptor and provide an
      overview of the ALX-LXA(4) axis responsible for anti-inflammatory and
      proresolving signals in vivo. The information in this review provides further
      support for the initial nomenclature proposition for this GPCR as ALX.

PMID- 16968949
TI  - Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use.
AB  - Cyclic nucleotide phosphodiesterases (PDEs) are enzymes that regulate the
      cellular levels of the second messengers, cAMP and cGMP, by controlling their
      rates of degradation. There are 11 different PDE families, with each family
      typically having several different isoforms and splice variants. These unique
      PDEs differ in their three-dimensional structure, kinetic properties, modes of
      regulation, intracellular localization, cellular expression, and inhibitor
      sensitivities. Current data suggest that individual isozymes modulate distinct
      regulatory pathways in the cell. These properties therefore offer the opportunity
      for selectively targeting specific PDEs for treatment of specific disease states.
      The feasibility of these enzymes as drug targets is exemplified by the commercial
      and clinical successes of the erectile dysfunction drugs, sildenafil (Viagra),
      tadalafil (Cialis), and vardenafil (Levitra). PDE inhibitors are also currently
      available or in development for treatment of a variety of other pathological
      conditions. In this review the basic biochemical properties, cellular regulation,
      expression patterns, and physiological functions of the different PDE isoforms
      will be discussed. How these properties relate to the current and future
      development of PDE inhibitors as pharmacological agents is especially considered.
      PDEs hold great promise as drug targets and recent research advances make this an
      exciting time for the field of PDE research.

PMID- 16968950
TI  - Pharmacogenetics, drug-metabolizing enzymes, and clinical practice.
AB  - The application of pharmacogenetics holds great promise for individualized
      therapy. However, it has little clinical reality at present, despite many claims.
      The main problem is that the evidence base supporting genetic testing before
      therapy is weak. The pharmacology of the drugs subject to inherited variability
      in metabolism is often complex. Few have simple or single pathways of
      elimination. Some have active metabolites or enantiomers with different
      activities and pathways of elimination. Drug dosing is likely to be influenced
      only if the aggregate molar activity of all active moieties at the site of action
      is predictably affected by genotype or phenotype. Variation in drug concentration
      must be significant enough to provide "signal" over and above normal variation,
      and there must be a genuine concentration-effect relationship. The therapeutic
      index of the drug will also influence test utility. After considering all of
      these factors, the benefits of prospective testing need to be weighed against the
      costs and against other endpoints of effect. It is not surprising that few drugs
      satisfy these requirements. Drugs (and enzymes) for which there is a reasonable
      evidence base supporting genotyping or phenotyping include
      suxamethonium/mivacurium (butyrylcholinesterase), and azathioprine/6
      mercaptopurine (thiopurine methyltransferase). Drugs for which there is a
      potential case for prospective testing include warfarin (CYP2C9), perhexiline
      (CYP2D6), and perhaps the proton pump inhibitors (CYP2C19). No other drugs have
      an evidence base that is sufficient to justify prospective testing at present,
      although some warrant further evaluation. In this review we summarize the current
      evidence base for pharmacogenetics in relation to drug-metabolizing enzymes.

PMID- 16968951
TI  - Inhibitors of brain phospholipase A2 activity: their neuropharmacological effects
      and therapeutic importance for the treatment of neurologic disorders.
AB  - The phospholipase A(2) family includes secretory phospholipase A(2), cytosolic
      phospholipase A(2), plasmalogen-selective phospholipase A(2), and calcium
      independent phospholipase A(2). It is generally thought that the release of
      arachidonic acid by cytosolic phospholipase A(2) is the rate-limiting step in the
      generation of eicosanoids and platelet activating factor. These lipid mediators
      play critical roles in the initiation and modulation of inflammation and
      oxidative stress. Neurological disorders, such as ischemia, spinal cord injury,
      Alzheimer's disease, multiple sclerosis, prion diseases, and epilepsy are
      characterized by inflammatory reactions, oxidative stress, altered phospholipid
      metabolism, accumulation of lipid peroxides, and increased phospholipase A(2)
      activity. Increased activities of phospholipases A(2) and generation of lipid
      mediators may be involved in oxidative stress and neuroinflammation associated
      with the above neurological disorders. Several phospholipase A(2) inhibitors have
      been recently discovered and used for the treatment of ischemia and other
      neurological diseases in cell culture and animal models. At this time very little
      is known about in vivo neurochemical effects, mechanism of action, or toxicity of
      phospholipase A(2) inhibitors in human or animal models of neurological
      disorders. In kainic acid-mediated neurotoxicity, the activities of phospholipase
      A(2) isoforms and their immunoreactivities are markedly increased and
      phospholipase A(2) inhibitors, quinacrine and chloroquine, arachidonyl
      trifluoromethyl ketone, bromoenol lactone, cytidine 5-diphosphoamines, and
      vitamin E, not only inhibit phospholipase A(2) activity and immunoreactivity but
      also prevent neurodegeneration, suggesting that phospholipase A(2) is involved in
      the neurodegenerative process. This also suggests that phospholipase A(2)
      inhibitors can be used as neuroprotectants and anti-inflammatory agents against
      neurodegenerative processes in neurodegenerative diseases.

PMID- 16968952
TI  - Theoretical basis, experimental design, and computerized simulation of synergism
      and antagonism in drug combination studies.
AB  - The median-effect equation derived from the mass-action law principle at
      equilibrium-steady state via mathematical induction and deduction for different
      reaction sequences and mechanisms and different types of inhibition has been
      shown to be the unified theory for the Michaelis-Menten equation, Hill equation,
      Henderson-Hasselbalch equation, and Scatchard equation. It is shown that dose and
      effect are interchangeable via defined parameters. This general equation for the
      single drug effect has been extended to the multiple drug effect equation for n
      drugs. These equations provide the theoretical basis for the combination index
      (CI)-isobologram equation that allows quantitative determination of drug
      interactions, where CI < 1, = 1, and > 1 indicate synergism, additive effect, and
      antagonism, respectively. Based on these algorithms, computer software has been
      developed to allow automated simulation of synergism and antagonism at all dose
      or effect levels. It displays the dose-effect curve, median-effect plot,
      combination index plot, isobologram, dose-reduction index plot, and polygonogram
      for in vitro or in vivo studies. This theoretical development, experimental
      design, and computerized data analysis have facilitated dose-effect analysis for
      single drug evaluation or carcinogen and radiation risk assessment, as well as
      for drug or other entity combinations in a vast field of disciplines of
      biomedical sciences. In this review, selected examples of applications are given,
      and step-by-step examples of experimental designs and real data analysis are also
      illustrated. The merging of the mass-action law principle with mathematical
      induction-deduction has been proven to be a unique and effective scientific
      method for general theory development. The median-effect principle and its mass
      action law based computer software are gaining increased applications in
      biomedical sciences, from how to effectively evaluate a single compound or entity
      to how to beneficially use multiple drugs or modalities in combination therapies.

PMID- 16968954
TI  - The role of intranasal corticosteroids in the management of pediatric allergic
      rhinitis.
AB  - Allergic rhinitis (AR) is currently the most common chronic disease in children
      in the United States, affecting as many as 40% of the children in the population.
      AR can substantially decrease a child's quality of life and can contribute to
      school absenteeism. Intranasal corticosteroids (INS) are thought to be the most
      effective treatment choice for controlling the symptoms of AR. However, parent
      and physician concerns over INS safety in children have often led to INS being
      used as a second-line treatment option. More recently, safety studies have shown
      that the newer INS agents have improved safety profiles compared with older INS
      agents. The newer INS drugs have been found to have minimal adverse effects on
      growth and hypothalamic-pituitary-adrenal-axis function in children, which is a
      concern when prescribing corticosteroids. This review will discuss the
      pathophysiology, diagnosis, and classification of AR. The mechanism of action,
      efficacy, and safety of INS will also be discussed by focusing on clinical
      evidence. Furthermore, other considerations, such as parent or caregiver
      education and patient compliance, will be reviewed.

PMID- 16968955
TI  - Evaluation and management of shunt infections in children with hydrocephalus.
AB  - Shunt infections constitute one of the main risks of shunt surgery for
      hydrocephalus, which is the single most common type of surgery performed by
      pediatric neurosurgeons. Infectious complications are responsible for increased
      morbidity and mortality, lengthy hospitalizations, and high cost. Most modern
      series report infection rates approaching 10% of all shunt procedures. Despite
      the high incidence of this complication, optimal management is still unknown, and
      research on prevention has been hampered by single-institution series and small
      numbers. This article will review the history, causes, presentation, management,
      and outcome from shunt infections in children. Pitfalls in diagnosis and
      management will be reviewed. Finally, prevention strategies and research
      questions still remaining in this area will be outlined.

PMID- 16968956
TI  - Is there an unconscious conspiracy against teenagers in the United States?

PMID- 16968957
TI  - Validation of a body mass index nomogram for children as an obesity screening
      tool in young children.

PMID- 16968958
TI  - Pill swallowing ability and training in children 6 to 11 years of age.
AB  - Despite the widespread view that children have difficulty swallowing pills, data
      are limited. In an observational cohort study, pill swallowing ability (small
      oral tablet) was assessed in children age 6 to 11 years. A total of 113 of 124
      subjects (91%) swallowed a tablet using an ordinary cup or a patented pill cup.
      All 57 subjects who initially said they could swallow a pill were capable. Forty
      seven learned with an ordinary cup and nine with the pill cup. Eleven did not
      learn. The majority of children (91%) age 6 to 11 years were able to successfully
      swallow a small oral tablet.

PMID- 16968959
TI  - Addressing behavioral health issues during well child visits by pediatric
      residents.
AB  - The study examined practices by pediatric residents (n = 61) concerning
      psychosocial care during well child visits. A random sample (n = 719) of well
      child visits was selected, and a medical record review was conducted. Results
      suggested that a behavioral health issue was discussed in 38% of the cases. The
      most frequent type of problem discussed involved a medical component, while
      problems with mood were rarely discussed (<1%). Residents treated 67% of the
      cases and referred 20% of the cases with behavioral health concerns. Logistic
      regression suggested that residents were significantly more likely to treat
      medically focused problems (P = 0.05), but more likely to refer children with
      social/environmental or learning problems (P = 0.05). Results suggested the need
      for further training in recognition of internalizing disorders.

PMID- 16968960
TI  - Multicenter, randomized, double-blind study comparing 20 and 40 mg of
      pantoprazole for symptom relief in adolescents (12 to 16 years of age) with
      gastroesophageal reflux disease (GERD).
AB  - An age-appropriate questionnaire (GASP-Q) was used to assess the frequency and
      severity of the gastroesophageal reflux disease (GERD) symptoms: abdominal/belly
      pain, chest pain/heartburn, pain after eating, nausea, burping/belching,
      vomiting/regurgitation, choking when eating, and difficulty swallowing, in
      adolescents age 12 to 16 years. The primary objective was to compare the mean
      composite symptom score (CSS) at week 8 with baseline after treatment with 20 or
      40 mg of pantoprazole. Statistically significant (p < 0.001) improvement in CSS
      occurred in both groups. Safety was comparable between the 2 groups. Pantoprazole
      was safe, well tolerated, and effective in reducing symptoms of GERD in
      adolescents.

PMID- 16968961
TI  - Clinician practice patterns: linking to community resources for childhood
      aggression.
AB  - Creating links to community resources for childhood aggression is one component
      of office-based violence prevention. Evidence is lacking regarding the effect of
      training clinicians to make these referrals and families' responses to them.
      Clinicians who received training (n=47) and parents (1093) were queried on the
      provision of referrals immediately after the visit. Fewer than half of clinicians
      (45%) reported making a community referral. A third of providers (37%) noted
      difficulty in identifying local resources. Training clinicians to utilize
      community resources for childhood aggression does not often result in creating
      community links for this purpose.

PMID- 16968962
TI  - Career goals in the high risk adolescent.
AB  - Possessing a career goal might serve as a protective factor for an adolescent's
      healthy development. This could be especially important in adolescents who engage
      in high risk behaviors. The relationship between high risk adolescents' future
      career goals and selected predictor variables were examined. Almost half (49%)
      the students indicated a career goal. Students who reported a job were 5.1-fold
      more likely to have listed a future career goal. Females, those aged 18 years,
      and those whose mothers were employed were twice as likely to have a career goal.
      Considerations for fostering career goals for high risk students are warranted.

PMID- 16968963
TI  - Unilateral benign testicular macro-orchidism in a child: decisions and dilemmas.

PMID- 16968964
TI  - Back pain.

PMID- 16968965
TI  - Acute renal failure.

PMID- 16968966
TI  - Won't Talk in School.

PMID- 16968967
TI  - Health inequities, environmental insecurity and the attainment of the millennium
      development goals in sub-Saharan Africa: the case study of Zambia.
AB  - The United Nations Millennium Development Goals (MDGs) are a series of 8 goals
      and 18 targets aimed at ending extreme poverty by 2015, and there are 48
      quantifiable indicators for monitoring the process. Most of the MDGs are health
      or health-related goals. Though the MDGs might sound ambitious, it is imperative
      that the world, and sub-Saharan Africa in particular, wake up to the persistent
      and unacceptably high rates of extreme poverty that populations live in, and find
      lasting solutions to age-old problems. Extreme poverty is a cause and consequence
      of low income, food insecurity and hunger, education and gender inequities, high
      disease burden, environmental degradation, insecure shelter, and lack of access
      to safe drinking water and basic sanitation. It is also directly linked to
      unsound governance and inequitable distribution of public wealth. While many
      regions in the world will strive to attain the MDGs by 2015, most of the
      countries in sub-Saharan Africa, with major human development challenges
      associated with socio-economic disparities, will not. Zambia's MDG progress
      reports of 2003 and 2005 show that despite laudable political commitment and some
      advances made towards achieving universal primary education, gender equality,
      improvement of child health and management of the HIV/AIDS epidemic, it is not
      likely that Zambia will achieve even half of the goals. Zambia's systems have
      been weakened by high disease burden and excess mortality, natural and man-made
      environmental threats and some negative effects of globalization such as huge
      external debt, low world prices for commodities and the human resource "brain
      drain", among others. Urgent action must follow political will, and some tried
      and tested strategies or "quick wins" that have been proven to produce high
      positive impact in the short term, need to be rapidly embarked upon by Zambia and
      other countries in sub-Saharan Africa if they are to achieve the Millennium
      Development Goals.

PMID- 16968968
TI  - Blood lead levels in children and environmental lead contamination in Miami inner
      city, Florida.
AB  - Studies have shown that the environmental conditions of the home are important
      predictors of health, especially in low-income communities. Understanding the
      relationship between the environment and health is crucial in the management of
      certain diseases. One health outcome related to the home environment among urban,
      minority, and low-income children is childhood lead poisoning. The most common
      sources of lead exposure for children are lead paint in older, dilapidated
      housing and contaminated dust and soil produced by accumulated residue of leaded
      gasoline. Blood lead levels (BLL) as low as 10 microg/dL in children are
      associated with impaired cognitive function, behavior difficulties, and reduced
      intelligence. Recently, it is suggested that the standard for intervention be
      lowered to BLL of 5 microg/dl. The objectives of our report were to assess the
      prevalence of lead poisoning among children under six years of age and to
      quantify and test the correlations between BLL in children and lead exposure
      levels in their environment. This cross-sectional analysis was restricted to 75
      children under six years of age who lived in 6 zip code areas of inner city
      Miami. These locations exhibited unacceptably high levels of lead dust and soil
      in areas where children live and play. Using the 5 microg/dL as the cutoff point,
      the prevalence of lead poisoning among the study sample was 13.33%. The study
      revealed that lead levels in floor dust and window sill samples were positively
      and significantly correlated with BLL among children (p < 0.05). However, the
      correlations between BLL and the soil, air, and water samples were not
      significant. Based on this pilot study, a more comprehensive environmental study
      in surrounding inner city areas is warranted. Parental education on proper
      housecleaning techniques may also benefit those living in the high lead-exposed
      communities of inner city Miami.

PMID- 16968969
TI  - Air quality management using modern remote sensing and spatial technologies and
      associated societal costs.
AB  - This paper presents a study of societal costs related to public health due to the
      degradation of air quality and the lack of physical activity, both affected by
      our built environment. The paper further shows road safety as another public
      health concern. Traffic fatalities are the number one cause of death in the
      world. Traffic accidents result in huge financial loss to the people involved and
      the related public health cost is a significant part of the total societal cost.
      Motor vehicle exhausts and industrial emissions, gasoline vapors, and chemical
      solvents as well as natural sources emit nitrogen oxides and volatile organic
      compounds, which are precursors to the formation of ground-level Ozone. High
      concentration values of ground-level Ozone in hot summer days produce smog and
      lead to respiratory problems and loss in worker's productivity. These factors and
      associated economic costs to society are important in establishing public policy
      and decision-making for sustainable transportation and development of communities
      in both industrialized and developing countries. This paper presents new science
      models for predicting ground-level Ozone and related air quality degradation. The
      models include predictor variables of daily climatological data, traffic volume
      and mix, speed, aviation data, and emission inventory of point sources. These
      models have been implemented in the user friendly AQMAN computer program and used
      for a case study in Northern Mississippi. Lifecycle benefits from reduced
      societal costs can be used to implement sustainable transportation policies,
      enhance investment decision-making, and protect public health and the
      environment.

PMID- 16968970
TI  - Evidence for environmental contamination in residential neighborhoods surrounding
      the defense depot of Memphis, Tennessee.
AB  - An interdisciplinary environmental assessment team from the Howard University
      Environmental Justice Partnership (HUEJP) conducted a site visit and assessment
      of the Defense Depot of Memphis, Tennessee in February of 2000. This depot was
      built in the late 1940's for storage of numerous chemicals and munitions. As the
      years progressed, many Memphis citizens have grown to believe that the activities
      and chemical stockpile located at this site have negatively affected the health
      environment of their residents. There is anecdotal evidence and documentation of
      numerous cancers and other illnesses in those local territories, and
      specifically, at the Memphis Depot site. Currently, this depot is closed and in
      remediation by the local government. Particularly, citizens of the Rozelle
      community have started a campaign to investigate any signs of exposure pathways
      to noted health risks. The HUEJP was contacted and asked to investigate the
      community concerns. Obliging to the request, we aimed to sample at three drainage
      sites and a residential site, talk to local citizens, and gain any additional
      information that would be helpful in relieving anxiety in the Rozelle community.
      Soil, sediment, and water samples were collected and analyzed for total organic
      carbon, inorganic anions, and heavy metals. These data show that for the four
      sites sampled, the highest concentrations of organic compounds and heavy metals
      were located either within a residential area or in an area with a direct
      transport pathway to the community. Atomic absorption analysis revealed
      detectable amounts of cadmium, lead and chromium metals at all sites with direct
      transport pathways into the residential community, with chromium concentrations
      being far in excess of the EPA standard limits.

PMID- 16968971
TI  - Novel functional association of serine palmitoyltransferase subunit 1-A peptide
      in sphingolipid metabolism with cytochrome P4501A1 transactivation and
      proliferative capacity of the human Glioma LN18 brain tumor cell line.
AB  - Some chemical modulators of cytochrome P4501A1, Cyp1A1, expression also perturb
      the activity of serine palmitoyltransferase, SPT, a heterodimeric protein
      responsible for catalyzing the first reaction in sphingolipid biosynthesis. The
      effect of altered SPT activity on Cyp1A1 expression has generally been attributed
      to changes in the composition of bioactive sphingolipids, generated downstream in
      the SPT metabolic pathway, but the precise mechanism remains poorly defined. A
      generally accepted model for chemical-induced transactivation of the Cyp1A1 gene
      involves intracellular signaling mediated by proteins including the
      arylhydrocarbon receptor, AhR, whose interaction with the 90 kilo Dalton heat
      shock protein, Hsp90, is essential for maintaining a high affinity ligandbinding
      receptor conformation. Because ligand-induced Cyp1A1 expression is important in
      the bioactivation of environmentally relevant compounds to genotoxic derivatives
      capable of perturbing cellular processes, binding to Hsp90 represents an
      important regulatory point in the cytotoxicity process. In the present study,
      based on evidence that indicates subunit 1 of serine palmitoyltransferase, SPT1,
      interacts with Hsp90, both ligand-induced Cyp1A1 transactivation and capacity for
      proliferation were evaluated using the wild type Glioma LN18 human brain cancer
      cell line and its recombinant counterparts expressing green fluorescent SPT1
      fusion proteins. Exposure to the prototypical Cyp1A1 inducer, 3
      methylcholanthrene, 3-MC, resulted in the translocation of SPT1 from a primarily
      cytoplasmic domain to sites of focal adhesion complexes. Immunolabel for Hsp90,
      which was dispersed throughout the cell, became primarily cytoplasmic, while the
      distribution of AhR remained unaffected. When compared to the wild type, cells
      transfected with recombinant SPT1-GFP vectors had significantly attenuated levels
      of 3-MC-induced Cyp1A1 mRNA, as determined by quantitative reverse transcription
      PCR. Although all the Glioma cell lines exhibited mitogenic proliferative
      response in dose response assay with the potent Cyp1A1 inducers 3-MC, 2,3,7,8-
      tetrachlorodibenzo-p-dioxin (TCDD) and benzo [k] fluoranthene, BKF, only the
      recombinant cell line designated - 75SPT1-GFP, which was transfected with a
      mutant deletion of SPT1, retained its proliferative capacity at the highest PAH
      doses used in this study. The results suggest that overexpressing SPT1 as a green
      fluorescent fusion protein has a modulating effect on the transactivation of
      Cyp1A1. This is possibly due to SPT1 interacting with Hsp90 to modulate AhR-Hsp90
      interaction, and altering downstream events such as in downregulating the
      transactivation and metabolic activity of Cyp1A1. This is supported by the fact
      that the -75SPT1-GFP recombinant cell line, with much lower capacity for Cyp1A1
      induction, exhibited sustained mitogenic response to high doses of AhR ligands,
      but not the Cyp1A1 inducible wild type. Conceivably, the effect mediated by SPT1
      on the AhR signaling pathway is an important underlying factor contributing to
      variability in Cyp1A1 gene expression and consequently, cytotoxic response to
      environmentally relevant compounds that pose risk to human health.

PMID- 16968972
TI  - Association between multi-level inorganic arsenic exposure from drinking water
      and skin lesions in China.
AB  - Arsenic is one of the most important toxicants in the environment. In Inner
      Mongolia of China, 300,000 residents are believed to be drinking water containing
      >50 microg/liter. Skin lesions have been known as the most common consequences
      resulting from chronic exposure to arsenic. To clarify the prevalence of arsenic
      induced skin lesions, it is important to assess the impact of this problem among
      the target population, and to make future planning. We evaluated the association
      between multi-levels inorganic arsenic exposure from drinking water and skin
      lesions in an arsenic-affected area in Inner Mongolia, China. One hundred nine
      and 32 subjects in high (>50 microg/liter) and low (<50 microg/liter) arsenic
      affected villages were recruited and had the detailed physical examination with
      special emphasis on arsenic-related skin lesions. Arsenic exposure was measured
      for each participant with respect to iAs concentration of primary well and the
      duration using the well. Arsenic-induced skin lesions including keratosis,
      pigmentation, and/or depigmentation were diagnosed in 56 and 3 subjects in the
      two villages, respectively. Logistic regression was conducted to calculate odd
      ratios of skin lesions associated with arsenic exposure with adjustments for sex,
      age group, smoking and duration of exposure. A consistent dose-response
      relationship between arsenic exposure level and skin lesion risk was observed.
      Compared to those with iAs concentration <50 microg/liter, the adjusted odds
      ratios of skin lesions for the subjects with 51-99, 100-149 and >150 microg/liter
      were 33.3% (OR =15.50, 95% CI: 1.53-248.70), 46.7% (OR =16.10, 95% CI: 3.73
      69.63) and 55.7% (OR= 25.70, 95% CI: 6.43-102.87), respectively. Duration of
      using well was not associated with increased risk of skin lesions in this
      population; (OR =1.68, 95% CI: 0.40-6.91 for 6-15 years, OR = 2.30, 95% CI: 0.58
      9.14 for over 15 years) compared with the duration of less than 5 years.

PMID- 16968947
TI  - The endocannabinoid system as an emerging target of pharmacotherapy.
AB  - The recent identification of cannabinoid receptors and their endogenous lipid
      ligands has triggered an exponential growth of studies exploring the
      endocannabinoid system and its regulatory functions in health and disease. Such
      studies have been greatly facilitated by the introduction of selective
      cannabinoid receptor antagonists and inhibitors of endocannabinoid metabolism and
      transport, as well as mice deficient in cannabinoid receptors or the
      endocannabinoid-degrading enzyme fatty acid amidohydrolase. In the past decade,
      the endocannabinoid system has been implicated in a growing number of
      physiological functions, both in the central and peripheral nervous systems and
      in peripheral organs. More importantly, modulating the activity of the
      endocannabinoid system turned out to hold therapeutic promise in a wide range of
      disparate diseases and pathological conditions, ranging from mood and anxiety
      disorders, movement disorders such as Parkinson's and Huntington's disease,
      neuropathic pain, multiple sclerosis and spinal cord injury, to cancer,
      atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma,
      obesity/metabolic syndrome, and osteoporosis, to name just a few. An impediment
      to the development of cannabinoid medications has been the socially unacceptable
      psychoactive properties of plant-derived or synthetic agonists, mediated by CB(1)
      receptors. However, this problem does not arise when the therapeutic aim is
      achieved by treatment with a CB(1) receptor antagonist, such as in obesity, and
      may also be absent when the action of endocannabinoids is enhanced indirectly
      through blocking their metabolism or transport. The use of selective CB(2)
      receptor agonists, which lack psychoactive properties, could represent another
      promising avenue for certain conditions. The abuse potential of plant-derived
      cannabinoids may also be limited through the use of preparations with controlled
      composition and the careful selection of dose and route of administration. The
      growing number of preclinical studies and clinical trials with compounds that
      modulate the endocannabinoid system will probably result in novel therapeutic
      approaches in a number of diseases for which current treatments do not fully
      address the patients' need. Here, we provide a comprehensive overview on the
      current state of knowledge of the endocannabinoid system as a target of
      pharmacotherapy.

PMID- 16968973
TI  - Combating the epidemic of obesity and cardiovascular disease: perspectives from
      school-aged children.
AB  - This study was designed to assess students' perceptions of the obstacles to
      positive dietary practices and increased physical activity and to solicit the
      students' recommendations for addressing and possibly reducing the negative
      practices that are associated with the rise in obesity and the development of
      cardiovascular diseases. Data for the study were obtained from the administration
      of the 2005 Project Health High School Survey (PHHSS) which measured the
      students' perceptions regarding obstacles to eating more nutritious, healthier
      foods and obstacles to participating in daily physical activity. The reasons for
      students' lack of interest in practicing more life-healthy behaviors are ranked
      and recorded. Some of the students indicated that they usually ate what they
      liked to eat, and the decision about what to eat was made because of the taste of
      the food without regard for any health consequence or negative health outcomes.
      Finding ways to reach these students at their young ages is the key to
      successfully combating the high prevalence of obesity and the development of
      other chronic diseases in childhood, as well as in adulthood.

PMID- 16968974
TI  - Implementation of a cardiovascular disease prevention program among school-aged
      children: a pilot study.
AB  - The objective of this study was to test students' knowledge of cardiovascular
      disease information and to determine if a carefully structured training program
      administered to high school students would increase their knowledge about
      cardiovascular disease and risk factors that are preventable. A pilot study was
      conducted during which fifty high school students from nine counties in the State
      of Mississippi were measured for their knowledge of hypertension both at baseline
      and after the completion of an intervention training activity. There were
      significant gains in knowledge between the pre-test and the post-test that the
      students completed. The gains in knowledge indicate that elimination of risk
      factors is possible if all health care and school-based prevention programs are
      implemented to positively impact changes in eating and physical activity
      behaviors. Students' involvement in such activities could translate into
      significant changes in risk factors at these ages and throughout their lifetime.
      It is widely accepted that these behavioral changes, if sustained into adulthood,
      could have the potential to influence cardiovascular risk reduction.

PMID- 16968976
TI  - Free radicals: emerging challenge in environmental health research in childhood
      and neonatal disorders.
AB  - Infants and children may undergo severe oxidative stress due to disease state,
      pre-existing nutritional status, frequent use of oxygen, and lower levels of
      antioxidant defenses. Antioxidant defenses, made up of intracellular and extra
      cellular components, work synergistically to prevent oxidative damage. Total
      antioxidant activity (TAA) was analyzed by method of ferric reducing antioxidant
      power assay (FRAP). Patients admitted in Pediatric Dept, RNT Medical College,
      Udaipur, India were selected for these studies. TAA level in neonates with
      hypoxic-ischemic-encephalopathy (HIE) stage III and in poor outcome cases was
      significantly low. Erythrocyte SOD activity level was low in pre-term neonates.
      TAA level in severely malnourished children at the time of hospital admission was
      low. This low antioxidant level in severely malnourished children could be multi
      factorial viz. low zinc, selenium, vitamin A & C deficiency, recurrent
      infections, elevated free iron and chronic starvation stage. Delayed recovery of
      oxidant injury may lead to delayed incomplete recovery at cellular level. In a
      study of 29 tuberculosis patients TAA level was found to be low in tubercular
      patients compared with control. TAA level decreased more in CNS tuberculosis
      compared with other system tuberculosis. In a study of nutritional tremor
      syndrome TAA, ascorbic acid and alpha-tocopherol levels were low during pre
      tremor phase compared with tremor phase (ATS). Pre-term neonates have
      incompletely developed antioxidant defenses and are deficient in vitamin E, which
      is normally derived from maternal circulation at the end of 3rd trimester.
      Therefore, decreased TAA level in HIE with poor outcome indicates addition of
      antioxidants in therapeutic strategy. Since rise in TAA in antioxidant
      supplemented group of severely malnutrition children was higher with good outcome
      compared with nonsupplemented group it would be prudent to supplement antioxidant
      during nutritional management. These studies have shown that health benefits can
      be obtained by children with a reduced risk of disease from supplements of
      antioxidant nutrients. The amounts of optimal supplements in these disorders,
      whether pharmacologic or large, are to be determined. Further work is needed to
      show whether modest increases in nutrient intakes in children with these
      disorders will delay or prevent the complications and improve the outcome.
      Therefore, available evidence regarding health benefits to be achieved by
      supplementing antioxidant nutrients is encouraging. Free radical injury and
      antioxidant deficiency is more common than what we think. Severely malnourished
      children and children suffering from chronic infections and diseases are at
      several fold increased risk of antioxidant deficiency and likely to suffer from
      free radical injury. Appropriate interventions are required in reducing the risk
      associated with these observations.

PMID- 16968977
TI  - Microbial diversity and bioremediation of a hydrocarbon-contaminated aquifer
      (Vega Baja, Puerto Rico).
AB  - Hydrocarbon contamination of groundwater resources has become a major
      environmental and human health concern in many parts of the world. Our objectives
      were to employ both culture and culture-independent techniques to characterize
      the dynamics of microbial community structure within a fluidized bed reactor used
      to bioremediate a diesel-contaminated groundwater in a tropical environment.
      Under normal operating conditions, 97 to 99% of total hydrocarbons were removed
      with only 14 min hydraulic retention time. Over 25 different cultures were
      isolated from the treatment unit (96% which utilized diesel constituents as sole
      carbon source). Approximately 20% of the isolates were also capable of complete
      denitrification to nitrogen gas. Sequence analysis of 16S rDNA demonstrated ample
      diversity with most belonging to the infinity, beta and gamma subdivision of the
      Proteobacteria, Bacilli, and Actinobacteria groups. Moreover, the genetic
      constitution of the microbial community was examined at multiple time points with
      a Functional Gene Array (FGA) containing over 12,000 probes for genes involved in
      organic degradation and major biogeochemical cycles. Total community DNA was
      extracted and amplified using an isothermal phi29 polymerase-based technique,
      labeled with Cy5 dye, and hybridized to the arrays in 50% formimide overnight at
      50 degrees C. Cluster analysis revealed comparable profiles over the course of
      treatment suggesting the early selection of a very stable microbial community. A
      total of 270 genes for organic contaminant degradation (including naphthalene,
      toluene [aerobic and anaerobic], octane, biphenyl, pyrene, xylene, phenanthrene,
      and benzene); and 333 genes involved in metabolic activities (nitrite and nitrous
      oxide reductases [nirS, nirK, and nosZ], dissimilatory sulfite reductases
      [dsrAB], potential metal reducing C-type cytochromes, and methane monooxygenase
      [pmoA]) were repeatedly detected. Genes for degradation of MTBE, nitroaromatics
      and chlorinated compounds were also present, indicating a broad catabolic
      potential of the treatment unit. FGA's demonstrated the early establishment of a
      diverse community with concurrent aerobic and anaerobic processes contributing to
      the bioremediation process.

PMID- 16968975
TI  - Examination of the food and nutrient content of school lunch menus of two school
      districts in Mississippi.
AB  - This study examined the diet quality of the school meals in two Mississippi
      school districts and compared them to the national guidelines. We examined the
      lunch menus of the two school districts that participated in the National School
      Lunch Program and School Breakfast Program focusing on food quality and assessing
      both healthy and unhealthy foods and eating behaviors. This analysis was
      completed through a computerized review used to accurately determine the nutrient
      content. Both the standard and the alternative meals provided by the cafeterias
      in the two school districts exceeded the minimum requirement for calories for all
      grade levels. The meals from the urban schools cafeteria provide more calories
      than meals from the cafeteria in the rural school district. Although schools
      believe that they are making positive changes to children's diets, the programs
      are falling short of the nutrient recommendations. Poor nutrition and improper
      dietary practices are now regarded as important risk factors in the emerging
      problems of obesity, diabetes mellitus, hypertension and other chronic diseases,
      with excessive energy intake listed as a possible reason. Dieticians, school
      professionals and other health care practitioners need to accurately assess
      energy intake and adequately promote a dietary responsible lifestyle among
      children.

PMID- 16968978
TI  - Analysis of oxygen transfer performance on sub-surface aeration systems.
AB  - The efficiency of oxygen transfer depends on many factors including the type,
      size and shape of diffusers and the tank geometry. In this paper, the effect of
      the depth of water in the tank and, the extension of coverage area of diffusers
      on each of oxygen transfer capacity (OC), efficiency (E) and, on a percentage of
      oxygen absorption (delta) is tested. Experimental procedure is adopted to
      evaluate the effect of these parameters. The results of the study showed that,
      both the depth of water and the extent of coverage area of diffuser had a
      significant effect on the tested parameters. The values of oxygen transfer
      capacity (OC) and efficiency (E) ranged from 18 to 170 grO2/m3. hr and from 2 to
      17 grO2/m3air, respectively; depending on the depth of water in tank and the
      ratio of diffusers coverage area. The percentage of oxygen absorption ranged from
      0.45-5.4% depending on the testing conditions. Specific mathematical models to
      describe the effect of each parameter were also derived. The exponential form of
      equation proved to be efficient in describing the effect of a depth water on
      oxygen transfer capacity (OC) whereas; the linear form of equation was good
      enough in representing the effect of the other parameters.

PMID- 16968979
TI  - Serum fetuin-A levels link inflammation and cardiovascular calcification in
      hemodialysis patients.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality in
      hemodialysis (HD). An elevated incidence of cardiovascular calcifications (CVC)
      is observed in HD. Fetuin-A is an important inhibitor of CVC. Reduced fetuin-A
      levels associate with inflammation and increased cardiovascular (CV) mortality in
      HD. In this study we investigated the association of fetuin-A levels and CVC.
      METHOD: We evaluated a cohort of 115 patients (67 males), aged 63 +/- 16 years
      with a HD vintage >or=9 months. Presence of CVC was assessed by ultrasound
      imaging of the abdominal aorta, common carotid arteries, bilateral ilio-femoral
      axis, aortic and mitral cardiac valves. The presence of CVC was analyzed as a CVC
      score (CVCS) (0-7) according to the number of CVC sites. Patients were arbitrary
      stratified in three groups: group I (CVCS = 0), group II (0 < CVCS < 6) and group
      III (CVCS >or= 6). Patients without CVC were younger, non-diabetic and with a
      negative history for CV events. RESULTS: Patients with evidence of CVC in more
      than 5 sites had lower serum fetuin-A levels (0.41 +/- 0.22 g/l) compared to
      patients with CVCS = 0 (0.51 +/- 0.17 g/l, p = 0.048). In addition a worse CVCS
      was associated with higher serum levels of C-reactive protein (p = 0.002) and
      fibrinogen (p < 0.001). Serum fetuin-A levels lower than 0.290 g/l were
      associated with higher risk of a worse CVCS, independently from traditional risk
      factors. CONCLUSION: Chronic inflammation in HD patients leads to lower serum
      fetuin-A levels. The present study confirms the independent and significant
      association between reduced serum fetuin-A levels and multi-site CVC in HD.

PMID- 16968980
TI  - Perfusion-weighted magnetic resonance imaging in acute intracerebral hemorrhage
      at baseline and during the 1st and 2nd week: a longitudinal study.
AB  - BACKGROUND AND PURPOSE: Ischemic penumbra has been suggested as a contributing
      mechanism to secondary neuronal injury in intracerebral hemorrhage (ICH).
      Preliminary data suggest the presence of perihematomal hypoperfusion within the
      first hours after acute ICH. Our objective was to elucidate perfusion changes in
      the perihematomal region over time using magnetic resonance imaging (MRI).
      METHODS: Two perfusion-weighted MRIs were studied prospectively in 18 ICH
      patients. All patients had an acute perfusion-weighted MRI within 24 h of the
      onset of symptoms (time 0); 11 patients had a follow-up study on day 7 (time 1),
      and 7 patients on days 10-14 (time 2). The region of interest (ROI) was placed
      over the penumbral area, on high-intensity FLAIR and perfusion overlapping map
      imaging. Clinical data were assessed at baseline (National Institutes of Health
      Stroke Scale) and on day 90 (Canadian Scale, modified Rankin Scale). RESULTS: The
      average hematoma volume was 56 (9-140) ml; 10 were located deeply, and 8 were
      lobar. When we compared the perfusion changes (mean transit time prolongation) in
      the perihematomal area (lesion ROI) relative to itself over time, we found
      significant differences only between times 0 and 2 (p = 0.05). There were also
      significant differences in mean transit time between the lesion ROI and the
      contralateral mirror ROI in the baseline study (p = 0.001), with a trend to
      significance for time 1. CONCLUSIONS: Our data confirm the presence of
      hypoperfusion around an acute ICH and demonstrate that this change disappears
      completely after the first week. These data suggest that further evaluation of
      this feature of acute ICH is warranted, as its confirmation may lead to
      modifications in the current therapeutic approach.

PMID- 16968981
TI  - Is 15 mm size criterion for lacunar infarction still valid? A study on strictly
      subcortical middle cerebral artery territory infarction using diffusion-weighted
      MRI.
AB  - BACKGROUND AND PURPOSE: The 'lacunar hypothesis' has been challenged, since small
      (diameter <15 mm) subcortical infarcts can be produced by middle cerebral artery
      disease (MCAD) or cardioembolism (CE), while a larger infarct can occur without
      evidence of MCAD or CE. We sought to assess whether the lacunar hypothesis based
      on size is still valid. METHODS: We studied 118 patients who were admitted within
      72 h after stroke onset and had acute deep subcortical MCA territory infarcts
      detected by diffusion-weighted MRI, and who had undergone angiography (mostly MR
      angiography). Stroke mechanisms were arbitrarily categorized regardless of lesion
      size: (1) MCAD when there was a corresponding MCA lesion; (2) internal carotid
      artery disease (ICAD) when there was a significant (>50%) ipsilateral ICAD; (3)
      CE when there was emboligenic heart disease without MCAD or ICAD, and (4) small
      vessel disease (SVD) when there was neither CE nor MCAD. SVD was further divided
      into definite SVD (dSVD, longest diameter <15 mm) or probable SVD (pSVD, longest
      diameter > or =15 mm). RESULTS: Seventy-three patients (62%) had SVD, of which 38
      (32%) had pSVD and 35 (30%) dSVD. Thirty-three patients (28%) had MCAD, five (4%)
      CE, and seven (6%) ICAD. The infarct diameter in MCAD was not larger than in SVD
      (p = 0.35), and there was no difference in clinical features or risk factors
      between MCAD and SVD, or between pSVD and dSVD. CE was distinguished from SVD by
      its larger size and cortical symptoms. CONCLUSIONS: There are no clinical and
      lesion-size differences between MCAD and SVD, suggesting that there seems to be
      no rationale for the 15 mm size criterion for lacunar or small-vessel infarction.

PMID- 16968982
TI  - Pulse pressure and mortality from cerebrovascular diseases in type 2 diabetic
      patients: the Verona Diabetes Study.
AB  - BACKGROUND/OBJECTIVE: Previous studies conducted both in the general and diabetic
      population have shown that pulse pressure (PP) can predict mortality from
      cardiovascular diseases. The aim of the present study was to investigate the
      relationship between PP and specific cardiovascular mortality, i.e. from
      cerebrovascular and ischemic heart diseases, in a well-characterized cohort of
      type 2 diabetic patients. METHODS: A cohort of 1,128 known type 2 diabetic
      patients 56 to 74 years of age with at least 2 blood pressure measurements for
      each year between 1984-1986 was followed-up for ten years to assess specific
      causes of death. The analyses were carried out by using the mean and the
      coefficient of variation (CV) of PP. RESULTS: By the end of the 10-year follow-up
      period, 375 patients (178 male, 197 female) had died (33%). The mean PP resulted
      as an independent predictor of all causes and cardiovascular mortality.
      Remarkably, the mean PP, but not the CV of PP, was highly predictive of mortality
      from cerebrovascular diseases. The risk of cerebrovascular mortality rose by 86%
      with a 10 mm Hg increase in mean PP. PP turned out to be the most important
      predictor of cerebrovascular mortality among various pressure indexes (mean,
      systolic and diastolic pressure). CONCLUSION: The mean pulse pressure, but not
      the coefficient of variation is a strong predictor of cardiovascular mortality,
      mainly from cerebrovascular diseases, in type 2 diabetic patients.

PMID- 16968983
TI  - Endothelial apoptosis does not determine symptom status in carotid artery
      disease.
AB  - BACKGROUND: We examined the hypothesis that endothelial denudation in advanced
      carotid plaques (CPs) occurs by increased apoptosis of endothelial cells (ECs)
      using scanning electron microscopy (SEM) as well as markers of cellular
      proliferation and apoptosis in advanced symptomatic CPs (SCPs) and asymptomatic
      CPs (ACPs). METHODS: 93 consecutive patients underwent carotid endarterectomy.
      Five additional specimens were studied by SEM. We performed TUNEL assays, and
      immunostaining against Fas receptor (FasR), Fas ligand (FasL), activated caspase
      3 (ACA3) and Ki-67. RESULTS: SEM revealed morphological changes consistent with
      EC detachment. Surprisingly, ACA3 positivity was more pronounced on the
      endothelium of ACPs (4.6 +/- 0.7% of total EC count) than on SCPs (3.3 +/- 0.7%,
      p = 0.049), and was found to correlate positively with nuclear Ki-67 expression
      (r(s) = 0.275, p = 0.040). FasL expression was significantly increased on the
      endothelium of SCPs compared with ACPs (66.4 +/- 4.4 vs. 53.9 +/- 4.5%, p =
      0.047). CONCLUSIONS: Absence of increased positivity of apoptotic markers
      dismisses apoptosis as a dominant mechanism underlying endothelial detachment of
      SCPs. Rather, increased ACA3 with co-expression of Ki-67 in ACPs might suggest
      that renewal of endothelium by active cell turnover may contribute to clinically
      silent evolution of plaques with preserved EC integrity. These observations may
      assist in designing novel therapies to prevent endothelial decay and symptom
      generation in advanced carotid artery disease.

PMID- 16968984
TI  - Deterioration of hemiparesis after recurrent stroke in the unaffected hemisphere:
      Three further cases with possible interpretation.
AB  - BACKGROUND: The concept of neural reorganization after brain damage is already
      well established, and many previous studies have successfully reported the
      translocation of the neural activation in the motor-related cortices during motor
      tasks using functional imaging modalities. Several primate and human studies have
      suggested the formation of newly reorganized tracts in the ipsilesional or
      contralesional hemisphere, but the mechanism for the formation of these tracts is
      still largely unknown. METHODS: Three acute stroke patients who presented with
      abrupt deterioration of their right-sided hemiparesis due to the infarcts
      following a recurrent stroke in the originally unaffected hemisphere were studied
      using magnetic resonance imaging (MRI), MR angiography and single-photon emission
      CT. The relationship between the neurological symptom on admission and the
      precise location of the new infarct was carefully investigated from the
      perspective of reorganization. RESULTS: Diffusion-weighted MRI showed a new
      subcortical infarct in the right hemisphere contralateral to the initial stroke
      in all patients. These new lesions involved the thalamus, globus pallidus or
      corona radiata, sparing the area of the internal capsule. T2-weighed MRI on
      admission showed an old infarct in the left middle cerebral artery territory,
      which had caused the original right-sided hemiparesis. CONCLUSION: It is proposed
      that the 'extrapyramidal' motor pathway in the unaffected hemisphere is
      associated with poststroke neural reorganization.

PMID- 16968986
TI  - The alanine/threonine polymorphism of the alpha-1-antichymotrypsin (SERPINA3)
      gene and ruptured intracranial aneurysms in the Japanese population.
AB  - BACKGROUND: Serine protease inhibitor member 3 of clade A (SERPINA3), also known
      as alpha-1-antichymotrypsin, inhibits the activity of cathepsin G. The release of
      neutrophil cathepsin G (proteolytic enzyme) can destroy the vascular matrix
      through degradation, platelet aggregation and coagulation disorders. In a
      previous report there was evidence that an alanine/threonine polymorphism was
      associated with the risk factor for aneurysmal subarachnoid hemorrhage (SAH) in a
      Polish population. We performed this study to determine whether this A15T
      polymorphism shows the same association in a Japanese population. METHODS: A
      total of 437 patients with an aneurysmal SAH and 405 control cases of Japanese
      origin were genotyped for the A15T polymorphism and 2 further intronic single
      nucleotide polymorphisms by using polymerase chain reaction and direct
      sequencing. RESULTS: In the patients with intracranial aneurysms the SERPINA3
      A15T allele and genotype distribution did not differ significantly from the
      controls. CONCLUSION: In the Japanese population the A15T polymorphism of the
      SERPINA3 gene is not associated with aneurysmal SAH.

PMID- 16968985
TI  - Is fatigue an independent factor associated with activities of daily living,
      instrumental activities of daily living and health-related quality of life in
      chronic stroke?
AB  - BACKGROUND: To determine the longitudinal association of poststroke fatigue with
      activities of daily living (ADL), instrumental ADL (IADL) and perceived health
      related quality of life (HRQoL) and to establish whether this relationship is
      confounded by other determinants. METHODS: A prospective cohort study of stroke
      patients consecutively admitted for inpatient rehabilitation was conducted. ADL,
      IADL and HRQoL were assessed in 223 patients at 6, 12 and 36 months after stroke.
      Fatigue was determined by the Fatigue Severity Scale. Random coefficient analysis
      was used to analyze the impact of fatigue on ADL, IADL and HRQoL. The association
      between fatigue and outcome was corrected for potential confounders, i.e. age,
      gender, comorbidity, executive function, severity of paresis and depression. The
      covariate was considered to be a confounder if the regression coefficient of
      fatigue on outcome changed by >15%. RESULTS: Fatigue was significantly related to
      IADL and HRQoL but not to ADL. The relation between fatigue and IADL was
      confounded by depression and motor impairment. Depression biased the relation
      between fatigue and HRQoL, but fatigue remained independently related to HRQoL.
      CONCLUSIONS: Fatigue is longitudinally spuriously associated with IADL and
      independently with HRQoL. These findings suggest that in examining the impact of
      poststroke fatigue on outcome, one should control for confounders such as
      depression.

PMID- 16968987
TI  - Asymmetric cerebral embolic load and postoperative cognitive dysfunction in
      cardiac surgery.
AB  - BACKGROUND: The aim of the study was to determine the effects of asymmetric
      cerebral embolic load on cognitive functions. METHODS: Thirty-six open heart
      surgery (OH) and 26 coronary artery bypass grafting (CABG) patients were
      evaluated by neuropsychological and transcranial Doppler tests. RESULTS: OH was
      associated with a significantly larger microembolic load in comparison to CABG.
      In OH patients, the microembolic load at the left middle cerebral artery
      correlated with a verbal memory decline, whereas the microembolic load at the
      right middle cerebral artery correlated with a nonverbal memory deficit. CABG
      patients also showed a postoperative verbal memory decline which correlated with
      cardiopulmonary bypass length but not with microembolic load. CONCLUSION: Massive
      microembolic load during OH induces specific cognitive impairment in accordance
      to the brain region to which they are delivered. In atherosclerotic patients, the
      left temporal region is especially prone to perioperative ischemia.

PMID- 16968988
TI  - Raised plasma aldosterone and natriuretic peptides in atrial fibrillation.
AB  - BACKGROUND AND AIMS: During atrial fibrillation (AF), the renin-angiotensin
      aldosterone system (RAAS) may be activated. In this study, our aim was to
      evaluate at a long-term follow-up visit the levels of plasma aldosterone and
      natriuretic peptides as markers of neurohormonal remodeling in patients with
      earlier, documented AF in relation to present heart rhythm, clinical data, and
      the left ventricular ejection fraction (LVEF). We hypothesized that increased
      levels of aldosterone and natriuretic peptides were significantly associated with
      present AF as markers of RAAS activation during the arrhythmia. METHODS: We
      studied 158 patients with earlier ECG-documented AF followed by restored sinus
      rhythm (SR) attending a follow-up visit 2.6 years (mean) after primary inclusion.
      RESULTS: At follow-up, 93 patients had SR. Heart rhythm at follow-up visit
      (SR/AF), plasma aldosterone, plasma N-terminal pro Brain Natriuretic Peptide (Nt
      proBNP), plasma N-terminal pro Atrial Natriuretic Peptide (Nt-proANP), LVEF,
      medication, and clinical characteristics were recorded. Standard linear multiple
      regression analysis including age, sex, weight, hypertension, congestive heart
      failure, ischemic heart disease, present AF at follow-up, total duration of AF
      disease, ongoing medication, and the LVEF as explanatory variables showed that
      only ongoing treatment with diuretics was significantly associated (likelihood
      ratio test, p = 0.0057) with a raised log-transformed plasma aldosterone,
      although present AF at follow-up was related to a high aldosterone level (p =
      0.09). For the natriuretic peptides, present AF at follow-up (p < 0.0001), age (p
      < 0.0001), female gender (p = 0.0047), ischemic heart disease (p = 0.0154), and
      ongoing treatment with sotalol (p = 0.0003) were all independently associated
      with high log-transformed plasma Nt-proANP. Likewise, present AF at follow-up (p
      = 0.0008) as well as age (p < 0.0001) were associated with high log-transformed
      plasma Nt-proBNP. CONCLUSIONS: In patients with earlier AF, AF at long-term
      follow-up visit was independently associated with raised levels of Nt-proANP and
      Nt-proBNP and to some extent with plasma aldosterone indicating neurohormonal
      activation during arrhythmia.

PMID- 16968989
TI  - Gene-based therapy for hypertension--do preclinical data suggest a promising
      future?
AB  - Many experimental studies have obtained a prolonged control of blood pressure
      through gene treatment. This consists in the administration of genes coding for
      vasodilator proteins (the 'sense' approach), or of nucleotide sequences that are
      complementary to the mRNA of vasoconstrictor proteins, which are consequently
      synthesized in smaller amounts (the 'antisense' approach). Examples of the sense
      approach include the genes encoding endothelial nitric oxide synthase and
      kallikrein. Examples of the second type of approach are the antisense
      oligodeoxynucleotides to angiotensin-converting enzyme and endothelin-1. Also,
      RNA molecules, such as ribozymes and small interfering RNAs, are capable to
      inhibit RNA function. Whole sense genes are usually administered through viral
      vectors, while antisense oligonucleotides may be administered with plasmids or
      liposomes. Both viral and non-viral vectors have advantages and disadvantages.
      Despite the still persisting limitations, the possibility exists that in the
      future some forms of genetic treatment will be extended to the clinical setting,
      allowing a prolonged control of essential hypertension and its end-organ
      sequelae.

PMID- 16968991
TI  - Results of two emergency room studies.
AB  - The aim of this paper is to examine to what extent cultural differences in male
      drinking patterns mediate relationships between alcohol and injury in a Polish
      context. Male patients admitted to emergency rooms located in two culturally
      different regions were investigated. Data analysis showed significant differences
      in patients' socio-demographic characteristics, their drinking patterns as well
      as their annual alcohol consumption. Logistic regression, however, has not
      confirmed any impact of site, drinking pattern and their interactions on the risk
      of injury. The risk of injury tended to decline with age, being more than two
      times lower for men over 50 years old, and was 2.4 times higher for those with an
      annual consumption of 12+ liters of pure alcohol.

PMID- 16968992
TI  - Italian survey of organizational functioning and readiness for change: a cross
      cultural transfer of treatment assessment strategies.
AB  - To better understand why some drug abuse treatment programs are more effective
      than others, USA research about organizational functioning and its role in the
      provision of treatment services was extended through a study of a delivery system
      in another country. The Texas Christian University (TCU) organizational
      functioning and readiness for change instrument (ORC) was translated into Italian
      and administered to 405 treatment program directors and staff from both public
      and private sectors in the Veneto Region of Northern Italy. Results indicated
      that the psychometric properties of the ORC in the USA and Italy are consistent.
      Some general differences in staff attributes were found between USA and Italian
      programs, but organizational climates were remarkably similar.

PMID- 16968993
TI  - Intercity differences in drug use by pre-teenage school children.
AB  - BACKGROUND: Regional variations in rates of drug use have been described
      previously in relation to adolescents. However, reasons for these differences are
      not clear. Previous publications pointed to higher rates of drug use by Glasgow
      children compared to children living in Newcastle upon Tyne. This paper explores
      the hypothesis that a higher rate of drug use in Glasgow is due to higher
      availability there. METHOD: School surveys were conducted in Glasgow and
      Newcastle upon Tyne on a total of 2,318 children aged 10-12. These concerned
      aspects of behaviour, lifestyle, family life and drug use. FINDINGS: The data
      indicate that the higher rate of drug use by Glasgow children was attributable to
      greater opportunities for children to gather at leisure centres and other venues
      and activities facilitating exposure to more drug-experienced young people.

PMID- 16968994
TI  - Substance use and substance use disorders in a community sample of adolescents
      and young adults: incidence, age effects and patterns of use.
AB  - OBJECTIVE: We present the prevalence and incidence rates of alcohol, nicotine,
      and illicit substance use, abuse, and dependence in a sample of German
      adolescents and young adults. Patterns of onset, cohort trends, and use of
      various substance classes are also analyzed. METHOD: A prospective longitudinal
      epidemiological study with a representative sample of adolescents and young
      adults (n = 3,021; baseline age range = 14-24 years) was conducted in Munich,
      Germany. Participants were assessed between 1995 and 1999 with the Munich
      Composite International Diagnostic Interview. RESULTS: Cumulative lifetime
      incidence (up to age 28) of any substance abuse or dependence was 43.8%, and 12
      month prevalence of any substance abuse or dependence was 24.4%. The lifetime
      incidence of nicotine dependence was most frequent (24.8%), followed by alcohol
      abuse (19.3%) and alcohol dependence (9.2%); 61.7% endorsed the regular use of a
      substance for at least one circumscribed period during their lifetime. Age
      specific incidence rates and age at onset of substance use disorders differed by
      age cohorts. Furthermore, nicotine dependence was significantly associated with
      illicit substance use disorders (HR = 2.6, 95% CI 1.7-4.0). An interactive
      relationship between age, age at onset of nicotine dependence, and subsequent
      onset of illicit substance use disorders was found. CONCLUSIONS: Since the
      baseline investigation in 1995, high incidence rates of substance use disorders
      and substance use have been observed in this young German sample. Especially
      younger cohorts report significantly earlier ages at onset of abuse and
      dependence. There also seems to be a trend towards a secondary age at onset peak
      of nicotine dependence after the onset of illicit drug use disorders. Further
      investigations are needed to study these patterns in younger samples. However,
      results emphasize the need for a combined prevention of illicit drugs and
      nicotine dependence.

PMID- 16968995
TI  - The relationship between legal status, perceived pressure and motivation in
      treatment for drug dependence: results from a European study of Quasi-Compulsory
      Treatment.
AB  - This paper reports on intake data from Quasi-Compulsory Treatment in Europe, a
      study of quasi-compulsory treatment (QCT) for drug dependent offenders. It
      explores the link between formal legal coercion, perceived pressure to be in
      treatment and motivation amongst a sample of 845 people who entered treatment for
      drug dependence in five European countries, half of them in quasi-compulsory
      treatment and half 'voluntarily'. Using both quantitative and qualitative data,
      it suggests that those who enter treatment under QCT do perceive greater pressure
      to be in treatment, but that this does not necessarily lead to higher or lower
      motivation than 'volunteers'. Many drug-dependent offenders value QCT as an
      opportunity to get treatment. Motivation is mutable and can be developed or
      diminished by the quality of support and services offered to drug-dependent
      offenders.

PMID- 16968996
TI  - Loss of flexibility in alcohol-taking rats: promoting factors.
AB  - Alcohol consumption in humans can move from a flexible pattern of intake to an
      inflexible (addictive) one. Several endogenous and exogenous factors are
      discussed to be involved in this transition. The purpose of this study was to
      examine factors that might promote the development of inflexibility. Over a
      period of 52 weeks (long-term) rats had continuously free choice between
      differently concentrated alcohol solutions and tap water (four-bottle paradigm).
      After 4 months of alcohol deprivation, a retest with free choice of alcohol was
      performed. Bitter-taste conditions were used to test the flexibility of alcohol
      taking. In the retest alcohol-experienced rats revealed a much higher alcohol
      intake than previously alcohol-naive ones. Part of the alcohol-experienced
      animals showed impairment of flexibility in alcohol taking. During long-term
      choice, some groups were submitted to experimental interventions that might
      affect addiction development (stress, withdrawal, limited access, adverse
      consequences). Rats with limited access to alcohol at the end of the long-term
      choice period took more alcohol and were less flexible in the retest than any
      other group. It is suggested that an unsatisfied urge for alcohol leads to
      impairment of control over alcohol drinking.

PMID- 16968997
TI  - Monitoring of alcohol and drugs under scrutiny: output and shortcomings.
AB  - A major focus of Dutch addiction policy is to improve the monitoring of substance
      use and addiction - which surveys and registrations are important for the
      monitoring of alcohol and drugs problems, and what information is generated or
      needs to be generated by these monitors? Three methods were used: an
      inventorisation of existing monitoring projects, a survey among experts in the
      field of alcohol and drugs to study the information needs, and a study on the
      output and shortcomings of the existing monitors. Sixty monitors and 13
      'umbrella' monitors were found. Experts formulated the needs of 11 topics which
      were matched with the output of the monitors. Coverage of the nature and extent
      of use in general is good. Shortcomings apply to the use and accessibility of the
      monitors, as well as to their completeness, standardisation and content.
      Especially questions with respect to problem use, treatment demand/need of help
      and user careers cannot be answered sufficiently with the existing information.

PMID- 16968998
TI  - Comparing injecting and non-injecting illicit opioid users in a multisite
      Canadian sample (OPICAN Cohort).
AB  - Illicit opioid use in Canada and elsewhere increasingly involves a variety of
      opioids and non-injection routes of administration. Injection and non-injection
      opioid users tend to differ in various key characteristics. From a public health
      perspective, non-injection routes of opioid use tend to be less harmful due to
      lesser morbidity and mortality risks. Our study compared current injectors (80%)
      and non-injectors (20%) in a multi-site sample of regular illicit opioid users
      from across Canada ('OPICAN' study). In bivariate analysis, injectors and non
      injectors differed by prevalence in social and health characteristics as well as
      drug use. Logistic regression analysis identified city, drug use, housing status
      and mental health problems as independent predictors of injection status. Further
      analysis revealed that the majority of current non-injectors had an injection
      history. Our results reinforce the need to explore potential interventions aimed
      at preventing the transition from non-injectors to injecting, or facilitating the
      transition of injectors to non-injecting, as initiated in several other contexts.

PMID- 16968999
TI  - Prenatal diagnosis of a fibrosarcoma of the thigh: a case report.
AB  - We report a rare case of fibrosarcoma of the thigh suspected prenatally. At 27
      weeks of gestation a voluminous, vascularised mass was discovered at ultrasound
      on the foetus' left leg, suggestive of haemangioma or a fibrosarcoma. There were
      no signs of heart failure. A rapid increase in the tumour mass was noted and a
      caesarean section was carried out at 39 weeks because of abnormal foetal heart
      rate. Postnatal ultrasound examination was comparable to that carried out
      prenatally; pathological examination of the mass biopsied and immunohistochemical
      investigation provided a diagnosis of congenital fibrosarcoma. After neoadjuvant
      chemotherapy and surgery the infant is now in complete remission without
      amputation.

PMID- 16969000
TI  - Retrospective diagnosis of Pallister-Killian syndrome by CGH array.
AB  - OBJECTIVE AND METHODS: We report a girl presenting with a polymalformation
      syndrome. Despite a normal karyotype on peripheral lymphocytes and the
      unavailability of cultured fibroblasts, a tetrasomy 12p was identified on
      pulmonary DNA extracted from a postmortem biopsy, by use of comparative genomic
      hybridization (CGH) and confirmed by CGH array. The clinical picture of our
      patient was consistent, but not specific of the diagnosis of Pallister-Killian
      syndrome. She presented with the association of antenatal polyhydramnios,
      craniofacial dysmorphic features, skeletal abnormalities, and a congenital
      cardiopathy. CONCLUSION: We discuss the usefulness of CGH and CGH array in
      prenatal and constitutional cytogenetics.

PMID- 16969001
TI  - Prenatal management of placental chorioangioma: value of the middle cerebral
      artery peak systolic velocity.
AB  - Placental chorioangiomas are benign tumors of the placenta. Large chorioangiomas
      may cause severe complications such as fetal anemia, hydrops and fetal death. We
      report the use of sonographic findings and peak systolic velocity in the middle
      cerebral artery in the diagnosis and management of fetal anemia without the
      occurrence of hydrops fetalis in a pregnant woman with a large placental
      chorioangioma. Successful intrauterine blood transfusion was performed at 26
      weeks. Spontaneous thrombosis of the main supplying blood vessel of the
      chorioangioma was detected at 33 weeks. The child was delivered at 39 weeks of
      pregnancy in normal clinical condition.

PMID- 16969002
TI  - Amnion cells engineering: a new perspective in fetal membrane healing after
      intrauterine surgery?
AB  - In this study we aimed to set up an in vitro culture of the rabbit amnion in
      order to support in vivo fetal membrane healing capacity following fetoscopy.
      Fetal membranes were collected from a mid-gestational rabbit, and cultured on
      collagen support material for 14 days. 34 rabbits at 22-23 days gestational age
      (GA) underwent fetoscopy. The entry site was randomly allocated to 4 closure
      technique study groups: group I, human amnion membrane (n = 23); group II,
      collagen foil (n = 16); group III, collagen plug (n = 19), and group IV, collagen
      plug with cultured amnion cells (n = 19). In all groups membrane access sites
      were additionally sealed with fibrin sealant, and the myometrium was closed with
      sutures. Fetal survival, amnion membrane integrity, and the presence of amniotic
      fluid were evaluated at 30 days GA. Cultures showed good survival in the collagen
      support material. Increased cellularity, survival and proliferations were
      observed. The amnion at the access site resealed in 58-64% of cases in groups II
      IV, but none of the tested techniques was significantly better than the other.
      Histological examination indirectly revealed the anatomic repair of the
      membranes, since no entrapment of the membranes could be demonstrated in the
      myometrial wound.

PMID- 16969003
TI  - Antenatal ultrasonographic appearance of isolated fetal ascites. A case report of
      sinus urogenitalis.
AB  - BACKGROUND: Isolated fetal ascites can be caused by many heterogeneous disorders
      and is associated with a variety of conditions. Cloacal anomalies are rare
      abnormalities with a highly variable array of sonographic symptoms, which make
      them difficult to diagnose antenatally. We present a case with isolated fetal
      ascites without hydronephrosis caused by a cloacal malformation. CASE: A 28-year
      old woman, gravida 2, para 1, was referred to our unit at 18 weeks gestation with
      a hyperdense structure in the fetal liver. Cordocentesis revealed a normal
      karyotype and negative viral titers. Isolated fetal ascites occurred for the
      first time at 23 weeks gestation. Serial ultrasounds showed progressive fetal
      ascites with no hydronephrosis at any time and no other malformations apart from
      the previously diagnosed hyperechogenic liver structure. After the insertion of
      an abdomino-amniotic shunt, a temporary reduction of the sonographically
      detectable ascites could be achieved. Cesarean delivery was necessary due to a
      pathological CTG at 33 weeks of gestation. The baby was born with a markedly
      distended abdomen. Postnatal radiologic examination showed two fistulae between
      the cloaca and the notedly dilated vagina and the rectum respectively. At the age
      of 3 months a vaginoplasty was performed, which involved creating a correctly
      positioned vaginal opening, reconstruction of the urethra and rectum as well as
      occlusion of the two fistulae. CONCLUSION: In view of the examinations, performed
      before and after delivery, it has to be assumed that fetal urine drained via the
      cloaca through the fallopian tubes into the abdomen. In contrast to usual
      appearance of cloacal malformations no hydronephrosis was detected and the kidney
      function was normal at all times. To our knowledge, this is the first published
      case of isolated fetal ascites without hydronephrosis caused by a cloacal
      malformation.

PMID- 16969004
TI  - Non-invasive prenatal detection of paternal origin hb lepore in a male fetus at
      the 7th week of gestation.
AB  - OBJECTIVE: To perform a reliable non-invasive prenatal detection of the Hb Lepore
      paternal mutation and determine the fetal gender in the first trimester of
      pregnancy. METHODS: DNA was extracted from a serum sample obtained from a
      pregnant woman at the mid first trimester of gestation. Hb Lepore-specific,
      mutant and normal, primers as well as Y-chromosome-specific STSs were used to
      carry out the analysis. RESULTS: Paternal Hb Lepore and the DYS14 and DYZ1 gene
      specific sequences were detected in the serum sample obtained at the 7th week of
      pregnancy. None of the above sequences was detectable in the maternal peripheral
      blood cell DNA. CONCLUSION: Conventional polymerase chain reaction analysis of
      cell-free fetal DNA can be used to determine fetal gender and paternal Hb Lepore
      as early as the 7th week of pregnancy.

PMID- 16969005
TI  - Prenatally diagnosable differences in the cellular immunity of fetuses with
      Down's and Edwards' syndrome.
AB  - INTRODUCTION: Lymphocyte subpopulations are identified by the uniform CD
      classification (Cluster of Differentiation) and can be accurately differentiated
      with monoclonal antibodies using the method of flow cytometry. With the aid of
      cordocentesis it is possible to perform studies on the status and development of
      cellular immunity as early as in the second trimester of pregnancy. OBJECTIVE: To
      compare lymphocyte subpopulations present in fetuses with chromosomal
      abnormalities (Down's syndrome (DS), Edwards' syndrome (ES)) and fetuses with
      normal karyotype. STUDY DESIGN: Prospective observational study. METHODS: We
      examined a total of 61 pregnant women with an average age of 31.5 years (20- 46
      years). RESULTS: In fetuses with DS we found a significant decrease in B
      lymphocytes (CD19),a decrease in the subpopulations of multi-reactive B-cells
      (CD5(+)CD19(+), B-CLL),and a decrease in the index of CD4/CD8 and class II HLA
      DR. In contrast, the representation of NK cells expressing /CD3-CD (16 + 56)+/
      was greatly increased. In ES we found a decrease in T lymphocytes (CD3), a
      decrease in T-helper lymphocytes (monocytes CD4), a decreased index of CD4/CD8
      and a greater representation of NK cells /CD3-CD (16 + 56)+/. CONCLUSION: We
      determined the normal values of lymphocyte subpopulations in physiological
      fetuses. We demonstrated that the immunological defect of the affected fetuses is
      already present antenatally, and can be reliably diagnosed in the second
      trimester of pregnancy.

PMID- 16969006
TI  - Prenatal diagnosis and postnatal management of diffuse congenital
      hyperinsulinism: a case report.
AB  - We present the first case of the prenatal diagnosis of congenital hyperinsulinism
      based on the genetic analysis of known family mutations in the SUR1 gene. An
      amniocentesis was performed at 16 weeks gestation at which time two mutations in
      the SUR1 gene were identified consistent with the diagnosis of diffuse
      hyperinsulinism. The mother was transported to our facility and underwent an
      elective caesarian section at 38 weeks gestation. The diagnosis was confirmed and
      treatment was initiated within the first minutes of life. After a short course of
      failed medical management, the patient underwent a 98% pancreatectomy with
      subsequent good glycemic control. This case highlights the benefits of the timely
      in utero diagnosis of hyperinsulinism by mutational analysis.

PMID- 16969007
TI  - Follow-up analysis of pregnancies complicated by HELLP syndrome.
AB  - AIM: In this study, we investigated the course of subsequent pregnancies in
      patients with HELLP syndrome and the development of chronic maternal diseases.
      RESULTS: The study population consisted of 50 patients who were treated for HELLP
      syndrome at 1(st) Department of Obstetrics and Gynecology, Semmelweis University
      between January 1, 1995 and December 31, 2004. There were 35 subsequent
      pregnancies in 25 patients. Of these there were seven miscarriages, one mid
      trimester loss. The incidence of premature birth was 40.7%, and neonatal
      mortality 7.4%. Preeclampsia recurred in twelve pregnancies; it was mild in eight
      and severe in four cases. HELLP syndrome re-occurred four times in three patients
      (14.28%). Recurrent hypertension was observed in 24% of the pregnancies.
      CONCLUSIONS: Pregnancies after a previous pregnancy complicated by HELLP syndrome
      carry not only an increased chance for HELLP syndrome but also the development of
      other pathological obstetric conditions and chronic maternal diseases.
      Hypertension was found to be a maternal disease of increased incidence (24%) in
      subsequent pregnancies.

PMID- 16969008
TI  - Automated microscopy of amniotic fluid cells: detection of FISH signals using the
      FastFISH imaging system.
AB  - OBJECTIVE: FISH (fluorescence in situ hybridization) analysis is a valuable
      adjunct to cytogenetics that provides a rapid screen for common abnormalities.
      However, FISH is expensive, labor-intensive, and requires a high skill level and
      subjective signal interpretation. A fully automated system for FISH analysis
      could improve laboratory efficiency and potentially reduce errors and costs.
      METHODS: In this study we blindly compared automated FISH signal acquisition and
      display against standard FISH analysis. A total of 62 amniocentesis samples were
      prepared using the AneuVysion multicolor DNA probe kit and probed for chromosomes
      13, 18, 21, X, and Y. Two sets of slides were produced from each sample. Fifty
      cells were scored in each slide. One set was evaluated using standard manual
      microscopy and the other using the automated image acquisition and display
      capabilities of the Ikoniscope fastFISH amnio Test System. This system uses
      epifluorescence optics, along with optimized slide management to process slides
      automatically. RESULTS: A 100% concordance was observed between the results
      obtained using manual microscopy and the automated system. There was also 100%
      concordance between the FISH results and those obtained by conventional
      karyotyping. CONCLUSION: Our data suggest that the automated system is capable of
      providing accurate and rapid identification and display of cells and FISH
      signals.

PMID- 16969009
TI  - The effectiveness of adrenocorticotropin repeated doses in high risk pregnancies.
AB  - OBJECTIVE: The aim of this study was to assess the effect of two kinds of
      adrenocorticotropin (ACTH)-depot repeated doses administered to pregnant women
      who underwent infertility treatment. MATERIAL AND METHODS: The study population
      included 424 pregnant women with singletons. Two hundred and forty-two women
      received repeated 0.5 mg doses of ACTH, whereas 182 women also were treated for
      infertility but did not receive any therapy. The ACTH-treated patients were
      subdivided into two subgroups: (1) 142 patients received only series of three 0.5
      g ACTH-depot injections every other day in the first and/or second trimester with
      occasionally single ACTH-depot doses in the third trimester, (2) 100 patients
      received only single 0.5 mg ACTH-depot doses for the entire duration of
      pregnancy. Clinical symptoms of threatened abortion and preterm delivery as well
      as very low or decreasing levels of serum oxytocinases were indications for the
      hormonal therapy. Low oxytocinase serum levels, recurrent abortion and preterm
      delivery characterize pregnant women with hypothalamic insufficiency. RESULTS:
      Women who received only single doses of the ACTH-therapy for the entire duration
      of pregnancy had a statistically significant longer gestation, and higher newborn
      mass and length than patients who received a series of three hormonal injections
      as well as control women who had no clinical or laboratory indication for such
      therapy. CONCLUSIONS: ACTH-depot injection results in the oxytocinase increased
      serum level, a decreased number of abortion and preterm deliveries and prolonged
      duration of pregnancy. Single repeated doses of the ACTH-depot therapy had
      statistically significant better results in the prolongation of pregnancy,
      newborn mass and length than a serial hormonal dosage.

PMID- 16969010
TI  - Intrauterine shunt for obstructive hydrocephalus--still not ready.
AB  - OBJECTIVE: To determine the safety and efficacy of ventriculoamniotic shunt
      placement through a hysterotomy in the second trimester of pregnancy as treatment
      for isolated obstructive hydrocephalus. METHODS: Between 1999 and 2003, four
      pregnancies with isolated fetal obstructive hydrocephalus in the second trimester
      were treated at Vanderbilt University Medical Center. Preoperatively, all fetuses
      underwent serial ultrasonographic examinations and an ultrafast magnetic
      resonance imaging to confirm isolated aqueductal stenosis. A normal fetal
      karyotype and negative polymerase chain reaction or culture of the amniotic fluid
      for cytomegalovirus and toxoplasmosis were obtained. Serial enlargement of the
      lateral ventricles >1.5 mm/week and fetal macrocephaly were documented. Using
      epidural and GETA, a standard ultrasmall ventricular catheter and valve were
      inserted via a hysterotomy. The distal catheter, rather than being inserted into
      the fetal peritoneum, exited between the fetal scapulae. Patients were discharged
      home from the hospital, and the remainder of their prenatal care was provided by
      their local obstetrician. After delivery, the distal drain was converted to a
      ventriculoperitoneal shunt. RESULTS: Cases were performed at 23 6/7, 25 5/7, 26
      4/7, and 26 5/7 weeks. Shunts performed well during pregnancy, and were intact at
      delivery. Deliveries occurred at 34 1/7, 27 1/7, 28, and 32 4/7 weeks.
      Birthweights were 2,010, 907, 1,200, and 2,220 g. All Apgar scores were normal.
      Case 1 developed a neonatal shunt infection, and is now developmentally delayed,
      with swallowing dysfunction, hearing deficits and a poor pupillary response. Case
      2 developed neonatal sepsis and is now developmentally delayed. Case 3 delivered
      preterm due to chorioamnionitis, and neonatal death occurred from sepsis. Case 4
      is developmentally delayed. CONCLUSIONS: Ventriculoamniotic shunt can be placed
      through a hysterotomy, overcoming many of the technical difficulties of earlier
      percutaneous shunts. However, recent developments in fetal imaging and molecular
      genetics have not improved case selection. Unless new breakthroughs occur, fetal
      shunting cannot reasonably be expected to improve perinatal outcome.

PMID- 16969011
TI  - A rare form of abruptio placenta and clinical presentation in a preterm labor
      case: Breus' mole.
AB  - A normotensive pregnant woman who had no historical risk factors for abruption
      placenta and found to have Breus' mole that indicates the pattern of single or
      multiple hematoma protrude above the chorionic plate was encountered. The case
      resembled a large fetal abdominal wall defect coexisting with a singleton live
      born fetus at 27 weeks of gestational age is presented. The obstetric ultrasound
      showed that multiple coiled masses in the amniotic cavity, both the fetus and the
      placenta were normal. After two courses of tocolysis therapy, a healthy and,
      1,400 g live-born infant was delivered through cesarean section due to fetal
      distress. Apgar scores at 1 and 5 min were 5 and 8, respectively. The infant died
      on postnatal day 6 due to severe respiratory distress and prematurity. This rare
      condition probably occurs frequently in missed abortion and the etiology is
      unknown, but is probably related to circulatory disturbance on maternal site. We
      report a rare clinical presentation and review the literature of Breus' mole.

PMID- 16969012
TI  - Diagnosis of Pentalogy of Cantrell by three-dimensional ultrasound in third
      trimester of pregnancy. A case report.
AB  - The Pentalogy of Cantrell is a rare congenital anomaly characterized by defects
      in the closing of the supraumbilical abdominal wall, in the anterior portion of
      the diaphragm, in the diaphragmatic pericardium, ectopia cordis, and intracardiac
      defects. It may be associated to other anomalies determining the variants of this
      syndrome. The prenatal ultrasound diagnosis is extremely important for detecting
      structural malformations and for postnatal surgical planning, when possible. We
      present a case of Pentalogy of Cantrell diagnosed in the 34th week of gestation,
      showing the main findings by two-dimensional ultrasound and emphasizing the
      importance of three-dimensional ultrasound on the assessment of structural
      malformations and on the better understanding of the origins of the pathology.

PMID- 16969013
TI  - [Malignant mesothelioma--diagnosis and treatment strategies].
AB  - Malignant mesothelioma originates from the mesothelial cells of the pleural and
      peritoneal cavities as well as the pericardium and tunica vaginalis, which is a
      devastating neoplasm with a strong etiological relationship with asbestos
      exposure. The incidence is rising worldwide, with the peak incidence in most
      industrialized counties expected to occur in the year 2020. Given the
      disappointing results of the single standard therapeutic modality, the
      combination of extrapleural pneumonectomy, chemotherapy, and radiotherapy has
      been attempted in order to reduce local recurrence and distal spread. Combined
      modalities have a better prognosis in selected patients with epithelioid
      histology, clear resection margins, and no positive extrapleural nodes.
      Chemotherapy using new antimetabolite agents in combination with platinum
      compounds is useful for palliation and can improve both survival and quality of
      life compared with single-agent cisplatin.

PMID- 16969014
TI  - [The progress of hepatic arterial infusion chemotherapy for hepatocellular
      carcinoma].
AB  - Hepatic arterial infusion (HAI) chemotherapy has been selected as a therapeutic
      option for highly advanced hepatocellular carcinoma (HCC) with tumor thrombi in
      major portal branches or intrahepatic metastases. Conventional therapies have no
      clinical effect on highly advanced HCC. Recent advances of an implanted
      portcatheter system have facilitated repeated arterial infusion of
      chemotherapeutic agents, and HAI chemotherapy with several anticancer drugs
      provides a useful choice for advanced HCC. In various regimens of HAI
      chemotherapy, low-dose cisplatin and 5-fluorouracil (5-FU) therapy or combination
      therapy of interferon (IFN)-alpha/5-FU have been reported to improve the response
      rates for advanced HCC. However, the survival benefit of HAI chemotherapy may be
      affected by liver function. None of these regimens have been proved to be the
      standard for HAI chemotherapy. We previously reported that the beneficial effects
      of combination therapy of IFN-alpha/5-FU for advanced HCC. IFN-alpha/5-FU
      combination therapy may be a promising treatment modality for advanced HCC.

PMID- 16969015
TI  - [Arterial infusion chemotherapy for patients with advanced pancreatic cancer].
AB  - Although various therapies have been tried to improve advanced nonresectable
      pancreatic cancer, a sufficient consensus has not yet been obtained about the
      treatment. We have performed arterial infusion chemotherapy for pancreatic cancer
      in order to maintain QOL. The response rate was 17.3%, the mean survival time
      282.1+/-204.7 days, median survival time 243.0+/-84.7 days, and many patients
      were continuously treated on an outpatient basis. It is thus expected that
      survival time and maintenance of QOL can be extended by self-sustaining arterial
      infusion chemotherapy.

PMID- 16969016
TI  - [Hepatic arterial infusion chemotherapy for liver metastases from digestive
      cancer].
AB  - Hepatic arterial infusion chemotherapy (HAIC) for liver metastases from digestive
      cancer has passed through a long history. In spite of its significant high tumor
      reduction rate, this therapeutic modality has been rejected as the first-line
      therapy for liver metastases from colorectal cancer because of the negative
      results of RCTs compared to systemic chemotherapy. However, recently some
      excellent results have been reported by the combination with systemic
      chemotherapy,and a positive result of RCT using a satisfactory study design has
      been reported. Thus, the combination with systemic chemotherapy and RCT in
      comparison with modern standard systemic chemotherapy as the first-line therapy
      remains an important problem to be solved. On the other hand, the highly
      developed technology for HAIC using techniques of interventional radiology has
      been standardized in Japan. Thus, we now have become the closest in the world to
      performing good-quality clinical trials of HAIC supported by high-quality
      technology. We should therefore consider our very important role in resolving
      such problems and deciding the future of HAIC.

PMID- 16969017
TI  - [Antitumor effects and clinical problems of transcatheter intraarterial infusion
      for uterine cervical cancer].
AB  - Several studies have confirmed that neoadjuvant chemotherapy and concurrent
      chemoradiation improved survival compared with standard therapy for uterine
      cervical cancer. There have been many reports on the use of transcatheter
      intraarterial infusion (TAI) with anticancer drugs, but there are no randomized
      controlled trials in Japan. Our study of transcatheter arterial infusion before
      operation or radiotherapy for uterine cervical cancer was performed for 49
      patients,and the number of patients with stage Ib (bulky tumor>3 cm), II, III, or
      IVa disease were 15, 18, 11, and 5, respectively. The drugs infused were
      cisplatin (100 mg/m(2)) or carboplatin (300 mg/m(2)). The median survival time, 2
      and 5-year survival rates were 62 months, 81.6%, and 70.6%, respectively. There
      were no grade 4 acute toxicities. As a late complication, ileus occurred in 8.2%.
      TAI may improve the prognosis of patients who underwent a radical operation after
      TAI.

PMID- 16969018
TI  - [Superselective intra-arterial infusion therapy with docetaxel, cisplatin and 5
      fluorouracil for head and neck cancer--for tongue cancer patients in comparison
      patients with other therapies].
AB  - In order to cure head and neck cancer without resection, chemotherapy
      (superselective intra-arterial infusion therapy with DCF) was conducted by
      anterograde, superselective intra-arterial infusion of 50-60 mg/m(2) of DOC and
      50-60 mg/m(2) of CDDP via the femoral artery on day 1 followed by continuous
      intravenous instillation of 600-750 mg/m(2)/day of 5-FU for 5 days from day 2. A
      total of 70 patients with advanced and recurrent cancer of the head and neck have
      been treated since April 2000. With the median follow-up duration of 1,017 days,
      the survival rate was 92.7% and the organ preservation rate was 90.1%. Almost no
      complications associated with this therapy were observed. Due to space
      limitations, here we report only cases of tongue cancer. Histological CR was
      obtained from all 19 patients with squamous cell cancer of the tongue. With the
      median follow-up duration of 1,371 days (45.7 months: 471-2, 133 days), the
      survival rate was 94.74% and the organ preservation rate was 88.42% by the Kaplan
      Meier method. For both the survival rate and organ preservation rate, extremely
      good results were obtained by the superselective intra-arterial infusion therapy
      with DCF compared to the intravenous infusion therapy using a combination of CDDP
      and 5-FU (five-year survival rate: 20%) as well as the superselective intra
      arterial infusion of CDDP alone followed by continuous intravenous infusion of 5
      FU (five year survival rate: 28.5%) that had been conducted before. Major adverse
      effects observed were leukopenia and alopecia. Although patients who underwent
      concurrent radiation therapy developed mucositis and dermatitis, both were
      reversible changes.

PMID- 16969019
TI  - [Retrospective evaluation of the safety of pamidronate administration at the dose
      of 90 mg/day/month in Japanese breast cancer patients with bone metastasis].
AB  - The Japanese Ministry of Health, Labor and Welfare approved the use of
      pamidronate in November 2004 at a dose of 90 mg/day/month especially for Japanese
      breast cancer patients with lytic bone metastasis. But no safety data have been
      shown for these Japanese patients thus far. Therefore, we evaluated the safety of
      pamidronate treatment for breast cancer patients with bone metastasis at the dose
      of 90 mg/day/month since July 1, 2004 until Dec 31, 2004, retrospectively, in our
      institute, the Shikoku Cancer Center. No definite severe side effects were
      detected in these patients, including renal dysfunction and thrombocytopenia. In
      addition, there were no definite alternations in hemoglobin titers, platelet
      counts, BUN, serum creatinine and potassium levels in one month and 3 months
      after beginning the treatment except for significant alternations in RBC counts
      in one month and in the serum calcium level 3 months later (p=0.03). Improvements
      of clinical symptoms or data due to bone metastases, i.e., bone pain or elevation
      of tumor markers, were obtained in 91% of patients. As a conclusion, pamidronate
      administration at the dose of 90 mg/day/month was safe for Japanese breast cancer
      patients with bone metastasis.

PMID- 16969020
TI  - [Long-term results of chemoradiation therapy for the patients with locally
      advanced (T4) esophageal cancer].
AB  - The prognosis of patients with advanced esophageal cancer is still poor.
      Recently, concurrent chemoradiation therapy for esophageal cancer is being
      utilized with increasing frequency. In this study, we reported concurrent
      chemoradiation for patients with T4 esophageal cancer. From July 2000, we treated
      21 consecutive patients with radiation and concurrent chemotherapy using
      intermittent low-dose FP chemoradiation (40 Gy radiation, 2 Gy/day, for 4 weeks
      280/m(2) 5-FU intermittent 24 continuous, CDDP 8 mg/m(2)/intermittent). All
      patients who underwent the treatment with concurrent CRT completed the planned
      chemoradiation. Out of 21 patients, 2 (9.5%) showed a complete response and 9
      patients (42.8%) showed a partial response. The 5-year survival rate of the T4
      patients with CRT was almost the same as for those who underwent surgery alone.
      Concurrent chemoradiation therapy for T4 esophageal cancer patients is feasible
      and seems to be a standard treatment for T4 esophageal cancer patients. The
      results indicated that CRT is an effective therapy for advanced esophageal
      cancer.

PMID- 16969021
TI  - [Clinical efficacy and safety of weekly paclitaxel therapy as second-line
      chemotherapy for patients with advanced and recurrent gastric cancer who were
      previously treated with TS-1 therapy].
AB  - The clinical efficacy and safety of weekly paclitaxel therapy were studied
      retrospectively in 17 patients with advanced and recurrent gastric cancer who had
      previously been treated with TS-1 therapy. The overall response rate was 0%, but
      MST was 495 days. The adverse effects observed were grade 3 leukopenia in 2
      patients (11.8%) and grade 1 and 2 alopecia in 13 patients (76.5%). However,
      weekly paclitaxel therapy was performed for all outpatients. Weekly paclitaxel
      therapy could be useful and safe as second-line chemotherapy.

PMID- 16969022
TI  - [Tailored-dose chemotherapy using gemcitabine for advanced pancreatic cancer].
AB  - Eighteen patients with metastatic or post-surgery recurrent pancreatic cancer
      were given weekly gemcitabine therapy. Almost all of these patients were aged or
      had other complications. We determined the individualized maximum repeatable dose
      (iMRD)as follows. We started at 500 mg/m(2) gemcitabine and repeated the
      treatment with an increase or a decrease of 100mg/m(2) each week, if the
      hematological toxicity was 0 or more than grade 1. If toxicity was grade 1, the
      same dose was given. And the third-week dose was an iMRD. Dose intensity was 286
      mg/m(2)/week. The median survival time was 262 days. Of these 18 patients, 2
      (11.1%), 11(61.1%) and 5 (27.8%) patients showed partial response, stable
      disease, and progressive disease, respectively. The therapeutic effects of iMRD
      equaled those of standard administration of gemcitabine.

PMID- 16969023
TI  - [Gemcitabine versus combined chemotherapy with 5-fluorouracil and cisplatin in
      advanced pancreatic cancer].
AB  - Gemcitabine hydrochloride (GEM) is a first-line therapeutic agent for advanced
      pancreatic cancer, but there is no established second-line treatment after GEM
      failure. We assessed the clinical benefit of systemic combined chemotherapy with
      5-fluorouracil and cisplatin (FP therapy) in 19 patients compared with GEM in 32
      patients, respectively. Tumor response rates were 10.5% and 15.6% for FP therapy
      and GEM, respectively. The median survival time in the FP therapy and GEM was 137
      days and 241 days, respectively. Although clinical benefit was similar in both
      types of therapy, median survival time was more favorable for GEM, especially for
      Stage IVb. Nausea and vomiting were the most commonly observed toxicity in the FP
      therapy group. Our data indicate that FP therapy is not considered to be a useful
      second-line agent in patients with GEM pretreated pancreatic cancer.

PMID- 16969024
TI  - [Evaluation of weekly low-dose CPT-11 combined with 5-FU/l-LV therapy for
      advanced and recurrent colorectal cancer--preliminary study].
AB  - In Japan, cancer chemotherapy for advanced and recurrent colorectal cancer has
      not been adequately developed in comparison with the USA and Europe. However, the
      number of patients with advanced colorectal cancer has increased dramatically in
      this decade. Therefore, effective and feasible regimens against colorectal cancer
      are urgently needed. We designed a new regimen to evaluate the efficacy and
      feasibility of weekly low dose CPT-11 combined with 5-FU/l-LV therapy based on an
      RPMI regimen against advanced and recurrent colorectal cancer. Twenty patients
      were enrolled in this study. Weekly administration (CPT-11; 60 mg/m(2) div for
      1st-line chemotherapy, 40 mg/m(2) div for 2nd-or 3rd-line chemotherapy, l-LV; 200
      mg/m(2) div, 5-FU; 500 mg/m(2) iv, 3 consecutive weeks, 1-week break) was
      performed on an ambulatory basis. The treatment cycles were repeated every 4
      weeks until disease progression and/or severe toxic events occurred. The overall
      response rate was 31.6% with 5.3% complete response and 26.3% partial response in
      addition to 42.1% with no changes beyond 3 months. These results suggested that
      the clinical benefit was shown in 73.7% of patients. Furthermore, median TTF
      (time to failure) of this regimen was 6.5 months and MST was 20.4 months,
      respectively. On the other hand, adverse events were restricted to grade 3 with
      30.0% neutorocytopenia and 5.0% thrombocytopenia. Therefore, weekly low-dose CPT
      11 combined with 5-FU/l-LV therapy seems to be extremely useful, with excellent
      anti-tumor effect and tolerable adverse reactions, for the treatment of advanced
      and recurrent colorectal cancer on an ambulatory basis.

PMID- 16969025
TI  - [Efficacy and safety of monotherapy with temozolomide in patients with anaplastic
      astrocytoma at first relapse--a phase II clinical study].
AB  - The efficacy and safety of temozolomide were evaluated in 32 patients with
      anaplastic astrocytoma at first relapse. Temozolomide was administered orally
      once daily for the first five days of a 28-day cycle, at a dose of 150 or 200
      mg/m(2)/day. The response rate determined by independent central review of MRI
      was 34% (95% confidence interval: 18.6%-53.2%), with 3 complete response and 8
      partial response. The rate of "no change or better" was 91% (95% confidence
      interval: 75.0%-98.0%). Progression-free survival (PFS) at 6 months was 40.6%,
      and the median PFS was 4.1 months. The incidence of constipation (50%) and nausea
      (25%) was high,but these events were all mild or moderate in severity except in
      one subject with constipation,and could be managed with standard laxatives and
      antiemetics. The main laboratory test abnormalities (total incidence and
      incidence of grade 3/4 change) were lymphocytopenia (50%, 25%), neutropenia (47%,
      6%), leukopenia (38%, 3%), thrombocytopenia (31%, 9%), and increased GPT (25%,
      3%). Temozolomide was shown to have good efficacy and tolerability in patients
      with anaplastic astrocytoma at first relapse.

PMID- 16969026
TI  - [A case of occult breast carcinoma with irradiation therapy and axillary lymph
      node dissection].
AB  - A 78-year-old woman was seen at the hospital for a swollen left axillary node.
      There was an elastic hard mass measuring 0.7 cm in diameter in the left axilla,
      but no breast mass was palpable in the bilateral breasts. Mammography did not
      reveal any tumor and calcification, and there was no abnormalities on breast
      ultrasonography (US), computed tomography (CT) and magnetic resonance imaging
      (MRI). Aspiration biopsy cytology of the left axillary node revealed
      adenocarcinoma. Systemic examination failed to reveal primary lesion. Thus, to
      make the diagnosis, we enucleated the axillary nodule. Immunohistochemical
      staining for the excisional specimen revealed an estrogen receptor, progesterone
      receptor and gross cystic disease fluid protein-15 (GCDFP-15) was strongly
      positive, so we diagnosed it as an occult breast carcinoma. After obtaining her
      informed consent, the patient underwent left axillary lymph node dissection and
      irradiation therapy of the left breast. The patient has been disease-free under
      adjuvant chemoendocrine therapy. We treated the occult breast carcinoma with
      radiation therapy of the breast and axillary lymph node dissection, and provided
      a review of the literature.

PMID- 16969027
TI  - [A case of HER2 overexpressing recurrent breast cancer treated clinically showing
      a complete response to trastuzumab/paclitaxel combination therapy].
AB  - A 57-year-old female was diagnosed as local, lung, and multiple liver metastases
      in the 2 years and 6 months after surgery. As expression of HER2 showed 3+, we
      performed trastuzumab/paclitaxel combination therapy. After 3 cycles, a rapid
      complete response was seen clinically. It is suggested that
      trastuzumab/paclitaxel combination therapy might be a first-line treatment for
      HER2 overexpressing recurrent breast cancer which had not been treated previously
      with anthracycline drugs.

PMID- 16969028
TI  - [Markedly effective regimen using bi-weekly trastuzumab and paclitaxel in an
      advanced breast cancer with multiple liver metastases].
AB  - A 69-year-old woman had a 7 x 6 cm tumor on her left breast with ipsilateral
      axillary lymph node swelling and multiple liver metastases as detected on CT scan
      (T 3 N 2 M 1 b, Stage IV). Core needle biopsy and immunohistochemistry of breast
      tumor showed invasive ductal carcinoma with negative hormone receptor and
      overexpression of HER 2. After a treatment failure of 3 months weekly trastuzumab
      monotherapy, a combination of bi-weekly trastuzumab and paclitaxel (weekly 6, bi
      weekly 9 courses), was given. Tumor markers became negative 4 months later, and
      multiple liver nodules, breast tumor and axillary nodes completely disappeared 9
      months later. Breast surgery was avoided, and CR was maintained more than 8
      months only with bi-weekly trastuzumab. From the standpoint of the patient's
      convenience,a bi-weekly schedule of trastuzumab and paclitaxel could be a
      promising treatment choice for metastatic breast cancer.

PMID- 16969029
TI  - [Two cases of recurrent breast cancer with regional lymph node metastases showing
      a complete response to trastuzumab and paclitaxel treatment].
AB  - We report two cases of recurrent breast cancer with regional lymph node
      metastases that responded completely to treatment with trastuzumab and
      paclitaxel. Case 1: A 52-year-old woman, who presented with left breast cancer,
      underwent mastectomy and axillary lymph node dissection in July 2002.
      Pathological findings were as follows: invasive ductal carcinoma (scirrhous
      type), 2.2 cm in size, histological grade 3, positive invasion to the lymphatic
      and blood vessels, negative nodal status (0/11), negative ER/PgR status, and
      overexpression of HER 2/neu. Left axillary lymph node metastasis was noted after
      five months, ie, in December 2002. Four cycles of chemotherapy with doxorubicin
      and cyclophosphamide were administered from January 2003; however, they were not
      effective. The patient showed a complete response after three months of
      chemotherapy with trastuzumab and paclitaxel. This treatment was stopped in
      September 2003. She has maintained a complete response for two and a half years
      and was not administered any further treatment as of February 2006. Case 2: A 59
      year-old woman, who presented with right breast cancer, underwent mastectomy and
      axillary lymph node dissection in May 2002. Pathological findings were as
      follows: invasive ductal carcinoma (scirrhous type), 1.8 cm in size, histological
      grade 2, positive invasion to the lymphatic and blood vessels, negative nodal
      status (0/5), positive ER and uncertain PgR status, and overexpression of HER
      2/neu. She had received adjuvant hormonal therapy with tamoxifen; however, a
      right supraclavicular lymph node metastasis was noted in October 2004. Treatment
      with exemestane was not effective. However, a complete response was observed with
      trastuzumab and paclitaxel for four months. She has maintained a complete
      response for six months and was not administered any further treatment as of
      February 2006.

PMID- 16969030
TI  - [A case of multi-drug resistant recurrent breast cancer with multiple bone
      metastasis responding to TS-1 and trastuzumab].
AB  - We experienced a case of multi-drug resistant recurrent breast cancer with
      multiple bone metastases achieving a significant improvement by TS-1 and
      trastuzumab. The prior treatments including taxane or vinorelbine and trastuzumab
      were changed in the regimen to TS-1 and trastuzumab because of the progressive
      disease. TS-1 was administered orally at 100 mg/day everyday for 2 weeks,
      followed by a 1-week rest interval as 1 cycle, and trastuzumab was injected at 2
      mg/kg/week for 4 weeks, followed by a 1-week rest interval as 1 cycle. After 3
      cycles of the treatment, the level of tumor markers and tumor sizes of bone
      metastases became reduced. In conclusion, the combination treatment of TS-1 and
      trastuzumab is thought to be effective for multi-drug resistant recurrent breast
      cancer.

PMID- 16969031
TI  - [A case of non-curatively resected gastric cancer successfully treated over 17
      months with TS-1 and irinotecan combination therapy].
AB  - We report a case of non-curatively resected gastric cancer successfully treated
      with TS-1 and irinotecan (CPT-11) combination therapy, resulting in long-term
      survival of 17 months. A 56-year-old woman underwent noncurative resection with
      total gastrectomy for advanced gastric cancer with severe lymph node metastasis
      on June 3, 2004. Postoperatively, She received TS-1 and CPT-11 combination
      therapy (TS-1 80 mg/m(2) day 1-21, CPT-11 80 mg/m(2) day 1, 15, every 5 weeks).
      However, due to grade 4 neutropenia, and grade 3 nausea and anorexia in the first
      course, both doses were reduced. Since then, no grade 3 or severer adverse
      reactions have been observed. After 5 courses, partial response to lymph node
      metastasis was obtained, and her quality of life was improved. Thus, TS-1 and CPT
      11 combination therapy has been effective for 17 months, suggesting that it is
      promising for long-term administration and survival to continue it perseveringly.

PMID- 16969032
TI  - [A case of advanced gastric cancer with peritoneal metastasis that responded to
      paclitaxel plus 5-FU therapy].
AB  - We report a case in which paclitaxel (PTX) plus 5-FU therapy was remarkably
      effective for advanced gastric cancer with peritoneal metastasis. The patient was
      a 41-year-old woman who had type 4 gastric cancer with peritoneal metastasis. PTX
      plus 5-FU therapy was performed. The regimen included 600 mg/body/day of 5-FU by
      continuous iv administration from day 1 to 5 and consequent administration of PTX
      (90 mg/body) on days 8, 15 and 22 for 28 days repetitively. After 4 courses were
      completed, abdominal CT revealed that ascites had disappeared and the stomach
      wall had become thinner. Thus,we considered the patient had a partial response,
      and performed total gastrectomy. After the operation, PTX plus 5-FU therapy was
      used for 8 courses with the same regimen. No serious adverse event was
      observed,and the patient maintained good QOL throughout the treatment. No sign of
      progressive disease was seen for 12 months after the operation. However, 18
      months after beginning the treatment, peritoneal metastasis became worse, and she
      died 19 months after treatment had begun. Considering the effectiveness and mild
      toxicity, PTX plus 5-FU therapy is thought to be useful for advanced gastric
      cancer.

PMID- 16969033
TI  - [A case of advanced gastric cancer with liver metastasis completely responding to
      CPT-11+low-dose 5-FU+CDDP chemotherapy].
AB  - The case was a 54-year-old man with type-3 gastric cancer in the cardia
      accompanied by multiple liver metastasis. He received combination chemotherapy
      consisting of CPT-11 (60 mg/body, day 1 and 8)+low-dose 5-FU and CDDP (5-FU 500
      mg/body/day and CDDP 5 mg/body/day, day 1-5 and 8-12, continuous infusion) every
      3 weeks. The initial 2 courses were administered on an inpatient basis,and
      further courses as an outpatient. After 7 courses of therapy without severe
      adverse events, not only primary lesion but also hepatic metastasis disappeared.
      He has been free from disease for 4 months, and chemotherapy was further
      continued with TS-1 (100 mg/body, day 1-14)+CPT-11 60 mg/body, day 1, 8), every 3
      weeks. CPT-11 in combination with low-dose 5-FU+CDDP can be one of the most
      effective regimens for unresectable advanced gastric cancer.

PMID- 16969034
TI  - [A case of N3 gastric cancer successfully treated by TS-1 followed by curative
      resection].
AB  - We report a case of N 3 gastric cancer successfully treated by TS-1 followed by
      curative resection. The patient was a 64-year-old male. Gastrointestinal
      endoscopic examination showed advanced gastric cancer. Examination by computed
      tomography revealed gastric cancer and swollen para-aortic lymph nodes. This
      patient was treated by neoadjuvant chemotherapy with oral administration of TS-1
      (120 mg/day, day 1-28 with 2 weeks rest). After 3 courses of TS-1, the primary
      lesion and swollen lymph nodes were remarkably reduced. This chemotherapy enabled
      pancreatoduodenectomy with D 3 lymph node dissection in curative resection. The
      pathological diagnosis was por, pT 2, pMP and pap, pT 1, pSM 2, pPM(-), pDM(-),
      pN 1, pStage II and curability A. This neoadjuvant chemotherapy regimen seems to
      be an effective and promising therapy for patients with advanced gastric cancer.

PMID- 16969035
TI  - [A resected case of effective treatment with TS-1 and CDDP for advanced gastric
      cancer with carcinomatous ascites].
AB  - We encountered a resected case of advanced gastric cancer after successful
      chemotherapy. The patient remained alive in good condition without any signs of
      recurrence at 2 years and 8 months after surgery. The 40-year-old woman initially
      complained of low abdominal pain, which was diagnosed as gastric cancer with
      metastasis of ovaries and carcinomatous ascites. We administered TS-1 (100
      mg/body/day) for 3 weeks followed by 2-week rest and CDDP (60 mg/body) on the 8th
      day of one cycle. After 3 cycles of treatment, carcinomatous ascites disappeared
      and the ovarian lesion was reduced. The patient underwent total gastrectomy,
      ileocecal resection, cholecystectomy and radical hysterectomy. The antitumor
      efficacy of the treatment was histologically Grade 2. We administered 17 cycles
      of TS-1 treatment, and the patient is alive in good condition at this writing.
      This shows that TS-1 and CDDP may have potent therapeutic efficacy in advanced
      gastric cancer patients. For the future, the safety and efficacious
      administration of TS-1 and CDDP should be examined further.

PMID- 16969036
TI  - [A patient with pancreatic cancer and multiple liver metastases after total
      pancreatectomy who showed a partial response to combination chemotherapy with
      gemcitabine and UFT].
AB  - A 69-year-old man underwent a complete pancreatectomy in March 2002 because of
      cancer of the body of the pancreas. Two months after surgery, the patient had
      multiple metastases to the liver, abdominal recurrence, and an elevated cancer
      antigen (CA) 19-9 level. Combination chemotherapy with gemcitabine and UFT was
      administered on an outpatient basis. Chemotherapy consisted of biweekly
      gemcitabine (1,000 mg/m(2)) and daily UFT (300 mg). After 3 months of treatment,
      a computed tomographic scan of the liver showed marked shrinkage of metastatic
      lesions, accompanied by a decrease in the CA19-9 level. The patient spent most of
      his time at home and worked as usual; his quality of life was maintained. The
      only adverse event was transient leukopenia (grade 2). He died of peritoneal
      dissemination in August 2003 (15 months after recurrence). Our experience
      suggests that combination chemotherapy with gemcitabine and UFT may promote tumor
      dormancy and relieve symptoms in patients with liver metastasis after surgery for
      pancreatic cancer or with recurrence of metastasis.

PMID- 16969037
TI  - [A case of non-curatively resected colon cancer with liver and lymph node
      metastases treated by TS-1/CPT-11 combination therapy].
AB  - The patient was a 66-year-old male who had descending colon cancer with multiple
      liver metastases and paraaortic lymph node metastases. He underwent a left
      colectomy with lymph node dissection, but the operation resulted in curability C.
      The serum CEA level before the operation was 205.5 ng/ml. After 2 courses of 5
      FU/LV as first-line chemotherapy, this treatment could not be continued due to
      grade 3 anorexia. As second-line chemotherapy, the patient was treated with daily
      oral administration of TS-1 (100 mg/day) for 3 weeks. Due to grade 3 anorexia,
      this treatment could not be continued. Tailored TS-1/CPT-11 (TS-1 80 mg/day from
      day 1 to day 21, CPT-11 65 mg/m(2) day 1, 15) combination therapy was then chosen
      as third-line chemotherapy. After 6 courses of combination therapy, the tumor
      marker (CEA) was decreased and para-aortic lymph nodes could not be detected by
      computed tomography (CT). Only grade 1 fatigue was noted as an adverse reaction
      to the treatment. The patient's good QOL was achieved during follow-up over 24
      months with the cancer controlled. This case suggests that patients with non
      curative resected colon cancer could benefit from TS-1/CPT-11 combination therapy
      as a second-line or third-line treatment.

PMID- 16969038
TI  - [A case of rectal cancer with multiple liver metastases responding to TS-1].
AB  - A 63-year-old woman was referred to our hospital with complaints of anal pain,
      constipation and abdominal distention caused by a rectal tumor. After
      examinations, she was diagnosed as rectal cancer with multiple liver metastases.
      The CEA level was 70.0 ng/ml and the CA19-9 level was more than 5,000 U/ml at
      admission. To prevent bowel obstruction, low anterior resection of the rectum was
      performed. At 34 days after operation, TS-1 chemotherapy was started as
      outpatient treatment (each course consisted of daily oral administration of 100
      mg TS-1 for 4 weeks followed by 2 drug-free weeks). After the first course, the
      CEA level was reduced to 3.3 ng/ml and the CA19-9 level to 15 U/ml, both under
      the normal value. After the second course, administration was discontinued due to
      diarrhea, and restarted as a daily oral administration of 80 mg TS-1. After the
      five courses, the CEA level was 4.0 ng/ml and the CA19-9 level was 4 U/ml, both
      under the normal value. Multiple liver metastases had remarkably reduced in the
      CT findings. The patient continues to undergo outpatient treatment with good QOL.

PMID- 16969039
TI  - [A case of advanced rectal carcinoma, preoperative chemo-radiation therapy
      leading to histological complete response].
AB  - A 49-year-old male was admitted to Sendai Saiseikai Hospital with a complaint of
      upper abdominal pain. Perforative rectal cancer was diagnosed, and an emergency
      laparotomy was done. Transient colostomy and drainage for peritonitis were
      performed. Preoperatively rectal cancer was assessed to invade the sacral bone
      and prostate. A total of 50 Gy radiation therapy with low dose CDDP+5-FU
      chemotherapy was conducted for five weeks. Remarkable shrinkage of the tumor was
      found, and elective surgery for curative intent was done on April 2000. The tumor
      seemed to invade the adjacent tissues such as prostate and urine bladder, so
      extensive resection of the urine bladder and sacral bone was done in addition to
      abdominal perineal resection. Pathological exploration showed complete regression
      of the tumor and no tumor invasion to the prostate and sacral bone. He is well
      without tumor relapse. Once complete regression of the rectal cancer by chemo
      radiation therapy has been achieved, relapse of the tumor was reported to be
      rare. Preoperative chemo-radiation therapy is an effective tool to control the
      advanced rectal cancer.

PMID- 16969040
TI  - [A case of local recurrence of rectal cancer in long-term responding to combined
      therapy of low-dose CPT-11 and 5'-DFUR].
AB  - A 68-year-old man underwent Miles'operation for advanced rectal cancer. Local
      recurrence occurred 9 months following the operation. We started the combined
      therapy of low-dose CPT-11 and doxifluridine (5'-DFUR). CPT-11 was administered
      at 80 mg/body biweekly and 5'-DFUR was orally administered at 800 mg/day/body on
      day 3-7. We then reduced the CPT-11 dose to 60 mg/body because of neutropenia.
      Four months later,we obtained a decrease in the tumor marker (carcinoembryonic
      antigen: CEA) to the normal serum level, and stopped the medication. However, 3
      months later the serum CEA level was increased, and we restarted the same
      therapy. Six months after restarting this therapy, the serum CEA level decreased
      to the normal level,and the local recurrence was decreased in size. We finished
      this combined therapy and changed to 5'-DFUR only. No tumor progression or
      recurrences in this patient are seen 2 years after completing this combined
      therapy.

PMID- 16969041
TI  - [Central venous catheter-related thrombosis with infection in cancer patients--2
      cases].
AB  - Cancer patients receive intensive chemotherapy by central venous catheter (CVC).
      Generally, there is a major risk of CVC-related thrombosis and infection due to
      their hematological and immunological status, respectively. Recently, catheter
      induced thrombosis caused by CVC-related bloodstream infection (BSI) has drawn
      attention in cancer patients. We observed a cohort of patients who received
      central venous catheterization for one year and described 2 cases of severe
      thrombosis associated with catheterization and its related infection. In both
      cases, neutropenic fever was followed by extended subcutaneous swelling with
      tenderness around the CVC-inserted site after intensive chemotherapy for
      malignant lymphoma. Chest CT revealed more severe thrombosis around the
      subclavian and cervical veins, but no mural thrombus on the contralateral site,
      in both cases. The thrombus included the air cavity, and was thought to be a sign
      of septic thrombi. Although the issue of the mechanism of infectious thrombosis
      associated with CVC insertion was not fully addressed, this rare but severe
      complication of CVC insertion should be studied descriptively and prevented by
      identification of risks and clinical signs.

PMID- 16969042
TI  - [Gemcitabine is an effective single agent for the treatment of advanced biliary
      tract cancer].
AB  - Gemcitabine, a novel nucleoside analogue, has shown broad clinical activity in a
      variety of malignant tumors and is currently used for the treatments of non-small
      cell lung cancer and pancreatic cancer in Japan. Based on the clinical results
      obtained in the early clinical trials in other locates, the safety profile was
      also established. Recently, the clinical usefulness of gemcitabine against
      advanced biliary tract cancer was approved in Japan. This means an important
      effective drug was developed against a well-known drug-refractory malignant
      neoplasm in Japan.

PMID- 16969043
TI  - MR imaging findings of ovarian cystadenofibroma: clues for making the
      differential diagnosis from ovarian malignancy.

PMID- 16969044
TI  - Comparison of 1.5T and 3T 1H MR spectroscopy for human brain tumors.
AB  - OBJECTIVE: We wanted to estimate the practical improvements of 3T proton MR
      spectroscopy ((1)H MRS) as compared with 1.5T (1)H MRS for the evaluation of
      human brain tumors. MATERIALS AND METHODS: Single voxel (1)H MRS was performed at
      both 1.5T and 3T in 13 patients suffering with brain tumors. Using the same data
      acquisition parameters at both field strengths, the (1)H MRS spectra were
      obtained with a short echo time (TE) (35 msec) and an intermediate TE (144 msec)
      with the voxel size ranging from 2.0 cm(3) to 8.7 cm(3). The signal to noise
      ratios (SNRs) of the metabolites (myoinositol [MI], choline compounds [Cho],
      creatine /phosphocreatine [Cr], N-acetyl-aspartate [NAA], lipid and lactate [LL])
      and the metabolite ratios of MI/Cr, Cho/Cr, Cho/NAA and LL/Cr were compared at
      both TEs between the two field strengths in each brain tumor. The degrees of
      spectral resolution between the Cho and Cr peaks were qualitatively compared
      between the two field strengths in each brain tumor. RESULTS: The SNRs of the
      metabolites at 3T demonstrated 49-73% increase at a short TE (p < 0.01) and only
      2-12% increase at an intermediate TE (p > 0.05) compared with those of 1.5T. The
      SNR of inverted lactate at an intermediate TE decreased down to 49% with poorer
      inversion at 3T (p < 0.05). There was no significant difference in the metabolite
      ratios between the two field strengths. The degrees of the spectral resolution at
      3T were slightly superior to those of 1.5T at a short TE. CONCLUSION: As compared
      with 1.5T, 3T 1H MRS demonstrated 49-73% SNR increase in the cerebral metabolites
      and slightly superior spectral resolution only at a short TE, but little at an
      intermediate TE, in the brain tumors. There was no significant difference in the
      metabolite ratios between the two field strengths.

PMID- 16969045
TI  - Structural brain abnormalities in juvenile myoclonic epilepsy patients: volumetry
      and voxel-based morphometry.
AB  - OBJECTIVE: We aimed to find structural brain abnormalities in juvenile myoclonic
      epilepsy (JME) patients. MATERIALS AND METHODS: The volumes of the cerebrum,
      hippocampus and frontal lobe and the area of the corpus callosum's subdivisions
      were all semiautomatically measured, and then optimized voxel-based morphometry
      (VBM) was performed in 19 JME patients and 19 age/gender matched normal controls.
      RESULTS: The rostrum and rostral body of the corpus callosum and the left
      hippocampus were significantly smaller than those of the normal controls, whereas
      the volume of the JME's left frontal lobe was significantly larger than that of
      the controls. The area of the rostral body had a significant positive correlation
      with the age of seizure onset (r = 0.56, p = 0.012), and the volume of the right
      frontal lobe had a significant negative correlation with the duration of disease
      (r = -0.51, p = 0.025). On the VBM, the gray matter concentration of the
      prefrontal lobe (bilateral gyri rectus, anterior orbital gyri, left anterior
      middle frontal gyrus and right anterior superior frontal gyrus) was decreased in
      the JME group (corrected p < 0.05). CONCLUSION: The JME patients showed complex
      structural abnormalities in the corpus callosum, frontal lobe and hippocampus,
      and also a decreased gray matter concentration of the prefrontal region, which
      all suggests there is an abnormal neural network in the JME brain.

PMID- 16969046
TI  - CT analysis of the anterior mediastinum in idiopathic pulmonary fibrosis and
      nonspecific interstitial pneumonia.
AB  - OBJECTIVE: We wanted to determine whether the amount and shape of the anterior
      mediastinal fat in the patients suffering with usual interstitial pneumonia (UIP)
      or nonspecific interstitial pneumonia (NSIP) was different from those of the
      normal control group. MATERIALS AND METHODS: We selected patients who suffered
      with UIP (n = 26) and NSIP (n = 26) who had undergone CT scans. Twenty-six
      controls were selected from individuals with normal CT findings and normal
      pulmonary function tests. All three groups (n = 78) were individually matched for
      age and gender. The amounts of anterior mediastinal fat, and the retrosternal
      anteroposterior (AP) and transverse dimensions of the anterior mediastinal fat
      were compared by one-way analysis of variance and Bonferroni's test. The shapes
      of the anterior mediastinum were compared using the Chi-square test. Exact
      logistic regression analysis and polychotomous logistic regression analysis were
      employed to assess whether the patients with NSIP or UIP had a tendency to show a
      convex shape of their anterior mediastinal fat. RESULTS: The amount of anterior
      mediastinal fat was not different among the three groups (p = 0.175). For the UIP
      patients, the retrosternal AP dimension of the anterior mediastinal fat was
      shorter (p = 0.037) and the transverse dimension of the anterior mediastinal fat
      was longer (p = 0.001) than those of the normal control group. For the NSIP
      patients, only the transverse dimension was significantly longer than those of
      the normal control group (p < 0.001). The convex shape of the anterior
      mediastinum was predictive of NSIP (OR = 19.7, CI 3.32-infinity, p < 0.001) and
      UIP (OR = 24.42, CI 4.06-infinity, p < 0.001). CONCLUSION: For UIP patients, the
      retrosternal AP and transverse dimensions are different from those of normal
      individuals, whereas the amounts of anterior mediastinal fat are similar. UIP and
      NSIP patients have a tendency to have a convex shape of their anterior
      mediastinal fat.

PMID- 16969047
TI  - Percutaneous treatment of failed native dialysis fistulas: use of pulse-spray
      pharmacomechanical thrombolysis as the primary mode of therapy.
AB  - OBJECTIVE: To determine the efficacy and outcome of percutaneous treatment in
      restoring the function of failed native arteriovenous fistulas (AVFs) where pulse
      spray pharmacomechanical thrombolysis was used as the primary mode of therapy.
      MATERIALS AND METHODS: From June 2001 to July 2005, 14 patients who had
      thrombosis of native AVFs underwent percutaneous restoration following 20
      episodes of thrombosis. These included 6 repeated episodes in one forearm AVF and
      two episodes in another forearm AVF. All patients except one were treated with
      urokinase injection utilizing the pulse-spray technique and had subsequent
      balloon angioplasty. One patient was treated by percutaneous angioplasty alone.
      We retrospectively evaluated the feasibility of percutaneous treatment in
      restoring the function of the failed AVFs. The primary and secondary patencies
      were calculated by using a Kaplan-Meier analysis. RESULTS: Both technical and
      clinical success were achieved in 15 (75%) of 20 AVFs. Four of the five technical
      failures resulted from a failure to cross the occluded segment. One patient
      refused further participation in the trial through a brachial artery access
      following failure to cross the occluded segment via an initial retrograde venous
      puncture. There were no major procedure related complications observed. Including
      the initial technical failures, primary patency rates at six and 12 months were
      64% and 55%, respectively. Secondary patency rates at six and 12 months were 71%
      and 63%, respectively. CONCLUSION: Pulse-spray pharmacomechanical thrombolysis
      for treatment of the thrombosed AVFs is safe, effective and durable. This
      procedure should be considered as an option for the management of failed AVFs
      prior to surgical intervention.

PMID- 16969048
TI  - Long-term results of percutaneous ethanol injection for the treatment of
      hepatocellular carcinoma in Korea.
AB  - OBJECTIVE: To evaluate the long-term follow-up results of percutaneous ethanol
      injection (PEI) for the treatment of hepatocellular carcinoma (HCC) in Korea.
      MATERIALS AND METHODS: Sixty-eight nodular HCCs initially detected in 64
      patients, were subjected to US-guided PEI as a first-line treatment. Long-term
      survival rates, local tumor progression rates, and complications were evaluated,
      as were the influences of tumor size and Child-Pugh class on these variables.
      RESULTS: No major complications occurred. The overall survival rates of the 64
      patients at three and five years were 71% and 39%, and their cancer-free survival
      rates were 22% and 15%, respectively. The overall survival rate of patients with
      a small HCC (< or =2 cm) was significantly higher (p = 0.014) than that of
      patients with a medium-sized HCC (< or =2 cm). The overall survival rate of
      patients with Child-Pugh class A was significantly higher (p = 0.049) than that
      of patients with Child-Pugh class B. Of 59 cases with no residual tumor, local
      tumor progression was observed in ablation zones in 18, and this was not found to
      be significantly influenced by tumor size or Child-Pugh class. CONCLUSION: The
      results of our investigation of the long-term survival rates of PEI in HCC
      patients in Korea (a hepatitis B virus-endemic area) were consistent with those
      reported previously in hepatitis C endemic areas. Patients with a smaller tumor
      or a better liver function exhibited superior survival rates.

PMID- 16969049
TI  - Diagnosis and follow-up US evaluation of ruptures of the medial head of the
      gastrocnemius ("tennis leg").
AB  - OBJECTIVE: The purpose of this study was to demonstrate the ultrasonographic (US)
      findings of rupture and the healing process of the medial head of the
      gastrocnemius ("Tennis Leg"). MATERIALS AND METHODS: Twenty-two patients (age
      range: 30 to 45 years) with clinically suspected ruptures of the medial head of
      the gastrocnemius were referred to us for US examination. All the patients
      underwent US of the affected limb and the contralateral asymptomatic limb. Follow
      up clinical evaluation and US imaging of all patients were performed at two-week
      intervals during the month after injury and at one-month intervals during the
      following six months. RESULTS: Of the 22 patients who had an initial US
      examination after their injury, partial rupture of the medial head of the
      gastrocnemius muscle was identified in seven patients (31.8%); the remaining 15
      patients were diagnosed with complete rupture. Fluid collection between the
      medial head of the gastrocnemius and the soleus muscle was identified in 20
      patients (90.9%). The thickness of the fluid collection, including the hematoma
      in the patients with complete rupture (mean: 9.7 mm), was significantly greater
      than that seen in the patients with partial tear (mean: 6.8 mm) (p < 0.01). The
      primary union of the medial head of the gastrocnemius with the soleus muscle in
      all the patients with muscle rupture and fluid collection was recognized via the
      hypoechoic tissue after four weeks. CONCLUSION: Ultrasonography is a useful
      imaging modality for the diagnosis and follow-up examination for the patients
      suffering with rupture of the medial head of the gastrocnemius.

PMID- 16969050
TI  - MR imaging findings of ovarian cystadenofibroma and cystadenocarcinofibroma:
      clues for the differential diagnosis.
AB  - OBJECTIVE: We wanted to assess the MR imaging findings of ovarian
      cystadenofibroma and cystadenocarcinofibroma, and we wanted to find clues for
      making the differential diagnosis between them. MATERIALS AND METHODS: The MR
      images of 12 pathologically proven cystadenofibromas and two
      cystadenocarcinofibromas were reviewed, with a focus on the internal
      architecture, signal intensity and enhancement. RESULTS: All the tumors appeared
      as multilocular cysts, except for a single unilocular cystic mass and a single
      solid mass. The previously reported characteristic MR findings of
      cystadenofibroma (a multilocular cystic mass with a T2-dark-signal-intensity
      solid component containing small cystic locules) were found in only 43% of the
      tumors (6/14). Diffuse or partial thickening of the cyst wall with T2-dark signal
      intensity without a definite solid component was as common as the previous
      reported findings (6/14). Two cystadenocarcinofibromas showed more prominent
      solid portions with higher T2-signal intensities and stronger enhancement than
      did the cystadenofibromas. CONCLUSION: Diffuse or partial thickening of the cyst
      wall with dark-signal-intensity in multilocular cystic masses may suggest ovarian
      cystadenofibroma, and this type of appearance may be as common as the previously
      reported characteristic appearance. A prominent solid component with a higher T2
      signal intensity and strong enhancement are the typical findings of
      cystadenocarcinofibroma.

PMID- 16969051
TI  - 3D multislice CT angiography in post-aortic stent grafting: a pictorial essay.
AB  - Helical CT angiography has been widely used in both pre- and post-aortic stent
      grafting and it has been confirmed to be the preferred modality when compared to
      conventional angiography. The recent development of multislice CT (MSCT) has
      further enhanced the applications of CT angiography for aortic stent grafting.
      One of the advantages of MSCT angiography over conventional angiography is that
      the 3D reconstructions, based on the volumetric CT data, provide additional
      information during follow-up of aortic stent grafting. While endovascular repair
      has been increasingly used in clinical practice, the use of 3D MSCT imaging in
      endovascular repair continues to play an important role. In this pictorial essay,
      we aimed to discuss the diagnostic performance of 3D MSCT angiography in post
      aortic stent grafting, including the most commonly used surface shaded display,
      curvilinear reformation, the maximum intensity projection, volume rendering and
      virtual endoscopy. The advantages and disadvantages of each 3D reconstruction are
      also explored.

PMID- 16969052
TI  - Transmural migration of surgical sponge evacuated by defecation: mimicking an
      intraperitoneal gossypiboma.
AB  - The spontaneous defecation of the surgical retained sponge is very rare. Here, we
      report a case of migrating surgical sponge that was retained in the colon and it
      was evacuated by defecation.

PMID- 16969053
TI  - Occlusion of traumatic carotid cavernous fistula by incidentally formed thrombus
      during the interventional procedure: a case report.
AB  - In this report, we present a rare case of traumatic carotid cavernous fistula
      that was occluded during the interventional procedure by incidentally formed
      blood clot. Sudden occlusion of the fistula and the resolution process of the
      precarious blood clot can be clearly seen on the serial angiogram.

PMID- 16969054
TI  - Hypertensive encephalopathy: isolated pons involvement mimicking central pontine
      myelinolysis.

PMID- 16969055
TI  - A successful experience of soil-transmitted helminth control in the Republic of
      Korea.
AB  - Soil-transmitted helminths (STH), namely Ascaris, Trichuris and hookworms
      (Ancylostoma and Necator), present a global health problem to about a half of the
      earthos population. In the Republic of Korea, STH were highly prevalent and were
      considered a high priority target for national control. To promote the control, a
      non-governmental organization named Korea Association for Parasite Eradication
      (currently Korea Association of Health Promotion) was founded in 1964, and mass
      fecal examination followed by selective mass chemotherapy with anthelmintics was
      performed twice a year from 1969 to 1995 targeting whole nationwide
      schoolchildren. Meanwhile, decreasing patterns of national STH infections have
      been monitored by 7 timeso quinquennial national surveys targeting general
      population. In 1971, the overall intestinal helminth egg positive rate was 84.3%
      (Ascaris 58.2%, Trichuris 65.4%, and hookworms 10.7%), which became 63.2% in
      1976, 41.1% in 1981, 12.9% in 1986, 3.8% in 1992, 2.4% in 1997, and 4.3% (Ascaris
      0.03%, Trichuris 0.02%, and hookworms 0%) in 2004. During the control period,
      national economy rapidly developed, and living standards including environment,
      sanitation, and agricultural technology greatly improved, which undoubtedly
      boosted the STH control effects. Our experience indicates that social driving
      force to establish an eligible national control system to conduct repeated mass
      chemotherapy, together with improvement of environment and sanitation, is
      important for initiating and achieving STH control in a developing community.

PMID- 16969056
TI  - Molecular and biochemical characterization of hemoglobinase, a cysteine
      proteinase, in Paragonimus westermani.
AB  - The mammalian trematode Paragonimus westermani is a typical digenetic parasite,
      which can cause paragonimiasis in humans. Host tissues and blood cells are
      important sources of nutrients for development, growth and reproduction of P.
      westermani. In this study, a cDNA clone encoding a 47 kDa hemoglobinase of P.
      westermani was characterized by sequencing analysis, and its localization was
      investigated immunohistochemically. The phylogenetic tree prepared based on the
      hemoglobinase gene showed high homology with hemoglobinases of Fasciola hepatica
      and Schistosoma spp. Moreover, recombinant P. westermani hemoglobinase degradaded
      human hemoglobin at acidic pH (from 3.0 to 5.5) and its activity was almost
      completely inhibited by E-64, a cysteine proteinase inhibitor.
      Immunohistochemical studies showed that P. westermani hemoglobinase was localized
      in the epithelium of the adult worm intestine implying that the protein has a
      specific function. These observations suggest that hemoglobinase may act as a
      digestive enzyme for acquisition of nutrients from host hemoglobin. Further
      investigations may provide insights into hemoglobin catabolism in P. westermani.

PMID- 16969057
TI  - Involvement of MAPK activation in chemokine or COX-2 productions by Toxoplasma
      gondii.
AB  - This experiment focused on MAPK activation in host cell invasion and replication
      of T. gondii, as well as the expression of CC chemokines, MCP-1 and MIP-1 alpha ,
      and enzyme, COX-2/prostaglandin E2 (PGE2) in infected cells via western blot,
      [3H]-uracil incorporation assay, ELISA and RT-PCR. The phosphorylation of ERK1/2
      and p38 in infected HeLa cells was detected at 1 hr and/or 6 hr postinfection
      (PI). Tachyzoite proliferation was reduced by p38 or JNK MAPK inhibitors. MCP-1
      secretion was enhanced in infected peritoneal macrophages at 6 hr PI. MIP-1 alpha
      mRNA was increased in macrophages at 18 hr PI. MCP-1 and MIP-1 alpha were reduced
      after treatment with inhibitors of ERK1/2 and JNK MAPKs. COX-2 mRNA gradually
      increased in infected RAW 264.7 cells and the secretion of COX-2 peaked at 6 hr
      PI. The inhibitor of JNK suppressed COX-2 expression. PGE2 from infected RAW
      264.7 cells was increased and synthesis was suppressed by PD98059, SB203580, and
      SP600125. In this study, the activation of p38, JNK and/or ERK1/2 MAPKs occurred
      during the invasion and proliferation of T. gondii tachyzoites in HeLa cells.
      Also, increased secretion and expression of MCP-1, MIP-1 alpha , COX-2 and PGE2
      were detected in infected macrophages, and appeared to occur via MAPK signaling
      pathways.

PMID- 16969058
TI  - Cytokine and antibody responses of reactivated murine toxoplasmosis upon
      administration of dexamathasone.
AB  - Toxoplasma gondii has been shown to result in life-threatening encephalitis in
      immunocompromised patients after reactivation of dormant parasites. In order to
      obtain information on immune responses related to this phenomenon, BALB/c mice
      were infected with 25 cysts of the 76K strain of T. gondii, then, treated orally
      with dexamethasone (Toxo/Dexa-treated group) in order to reactivate the chronic
      toxoplasmosis. None of the T. gondii-infected mice died during the experimental
      periods, whereas the Toxo/Dexa-treated mice evidenced a significant attenuation
      of survival periods. Toxoplasma-specific IgG2a, IgA and IgM titers in sera were
      significantly depressed in the Toxo/Dexa-treated mice; however, the IgG1 sera
      titers were similar to those seen in the Toxoplasma-infected mice. The
      percentages of CD4+ and CD8 alpha + T cells in the Toxo/Dexa-treated mice were
      significantly reduced 2 weeks after dexamethasone treatment. IFN-gamma and IL-10
      production levels in the Toxo/Dexa-treated mice were depressed significantly,
      whereas IL-4 production was increased temporarily. The expression levels of the
      Toxoplasma-specific P30 and B1 genes were found to have been increased in the
      Toxo/Dexa-treated mice in comparison with the Toxoplasmainfected mice.
      Collectively, the findings of this study demonstrate that reactivation of murine
      toxoplasmosis as the result of dexamethasone treatment induced a depression in
      Th1 immune responses, whereas Th2 immune responses were not significantly
      influenced.

PMID- 16969059
TI  - Safety and tolerability of elubaquine (bulaquine, CDRI 80/53) for treatment of
      Plasmidium vivax malaria in Thailand.
AB  - We conducted a study to compare the safety and tolerability of anti-relapse drugs
      elubaquine and primaquine against Plasmodium vivax malaria. After standard
      therapy with chloroquine, 30 mg/kg given over 3 days, 141 patients with P. vivax
      infection were randomized to receive primaquine or elubaquine. The 2 treatment
      regimens were primaquine 30 mg once daily for 7 days (group A, n = 71), and
      elubaquine 25 mg once daily for 7 days (group B, n = 70). All patients cleared
      parasitemia within 7 days after chloroquine treatment. Among patients treated
      with primaquine, one patient relapsed on day 26; no relapse occurred with
      elubaquine treatement. Both drugs were well tolerated. Adverse effects occurred
      only in patients with G6PD deficiency who were treated with primaquine (group A,
      n = 4), whose mean hematocrit fell significantly on days 7, 8 and 9 (P = 0.015,
      0.027, and 0.048, respectively). No significant change in hematocrit was observed
      in patients with G6PD deficiency who were treated with elubaquine (group B, n =
      3) or in patients with normal G6PD. In conclusion, elubaquine, as anti-relapse
      therapy for P. vivax malaria, was as safe and well tolerated as primaquine and
      did not cause clinically significant hemolysis.

PMID- 16969060
TI  - Travelers' malaria among foreigners at the Hospital for Tropical Diseases,
      Bangkok, Thailand - a 6-year review (2000-2005).
AB  - We retrospectively examined the charts of travelers admitted to the Hospital for
      Tropical Diseases, Bangkok, Thailand, with malaria during the years 2000-2005.
      Twenty-one cases of malaria were identified, of which 12 (57%) were Plasmodium
      vivax infections and 9 (43%) were P. falciparum infections. There was one mixed
      case with vivax and falciparum infection. Only 1 P. falciparum case had
      complications. All cases were successfully treated with standard antimalarial
      drugs. Only 3 of the 21 cases were thought to be acquired in Thailand, the rest
      were regarded to be imported.

PMID- 16969061
TI  - Cloning of the novel putative apoptosis-related gene of Spirometra erinacei
      (Order Pseudophyllidae).
AB  - We postulated that apolysis was processed in accordance with apoptotic changes
      occurring in a cestode, Spirometra erinacei (Pseudophyllidea). We cloned the
      novel putative apoptosis-associated gene from S. erinacei via screening of a S.
      erinacei cDNA library with a ced-3 gene (activator of apoptosis) probe from
      Caenorhabditis elegans. We identified a 261-bp cDNA sequence, which encodes for
      an 86-amino acid protein. The cloned gene expression was observed in the neck and
      gravid proglottids via Northern blotting, using cloned cDNA inserts as probes,
      but the clone was not expressed in any of other tissues. We suggest that this
      gene may be involved in the apolysis of S. erinacei during normal tissue
      development and differentiation in cestode parasites.

PMID- 16969062
TI  - In vitro protoscolicidal effects of hypertonic glucose on protoscolices of
      hydatid cyst.
AB  - To evaluate the protoscolicidal effects of various concentrations of hypertonic
      glucose, live protoscolices of sheep were exposed to 10%, 15%, 25% and 50%
      glucose solutions. Cetrimide (0.5%), silver nitrate (0.5%) and hypertonic saline
      (20%) were used as positive controls, while physiological saline was used as a
      negative control. After 1, 2 and 5 min, the protoscolicidal effects were
      determined by 1% eosin. A 25% glucose solution had no significant protoscolicidal
      effect. However, a 50% glucose solution revealed higher protoscolicidal effect
      than 0.5% silver nitrate but weaker effect than 0.5% cetrimide; the effect was
      comparable with that of 20% hypertonic saline. The results showed that hypertonic
      glucose solution is highly effective in killing protoscolices of Echinococcus
      granulosus in vitro.

PMID- 16969063
TI  - Infection status of pond smelts, Hypomesus olidus, and other freshwater fishes
      with trematode metacercariae in 6 large lakes.
AB  - In order to determine the current infection status of pond smelts, Hypomesus
      olidus, and other freshwater fishes with trematode metacercariae, a total of
      4,861 pond smelts and 18 other freshwater fishes, collected from the Soyang and
      Uiam Lakes in Gangwon-do, the Unam Lake in Jeollabuk-do, the Jangseong Lake in
      Jeollanam-do, the Uirim-ji (lake) in Chungcheongbuk-do, and the Andong Lake in
      Gyeongsangbuk-do, were individually digested with 1% pepsin-HCl and examined
      under a dissecting microscope. In all pond smelts caught from the 6 lakes, we
      were unable to detect any known human infectious trematode metacercariae in
      Korea. However, in other freshwater fishes, such as, Squalidus japonicus coreanus
      (Unam Lake), and Zacco platypus (Jangseong Lake) and Opsariichthys uncirostris
      amurensis (Jangseong Lake), metacercariae of human-infecting trematodes, i.e.,
      Clonorchis sinensis and Metagonimus sp. were detected, respectively.

PMID- 16969064
TI  - Egg positive rate of Enterobius vermicularis among preschool children in
      Cheongju, Chungcheongbuk-do, Korea.
AB  - In an attempt to determine the prevalence of pinworm infection, the egg positive
      rate of Enterobius vermicularis was examined using the adhesive cello-tape anal
      swab method in 1,512 preschool children sampled from a total of 20 kindergartens
      in Cheongju city, in November to December of 2004 (951 children from 13
      kindergartens) and September to October of 2005 (561 from 7 kindergartens). The
      overall egg positive rate was found to be 7.9% (119/1,512); 9.3% (73/784) for
      boys and 6.3% (46/728) for girls, respectively. The 5-year age group evidenced
      the highest egg positive rate (10.9%, 47/430) among the examined age groups. As
      compared to those reported from previous works (ranged from 9.2 to 26.1%), the
      prevalence of E. vermicularis in the Cheongju city area is relatively low.

PMID- 16969066
TI  - Field trial on the control effect of fipronil bait against German cockroaches.
AB  - A field trial on the control effect of fipronil poison bait against German
      cockroaches (Blatella germanica) was carried out at different restaurant types in
      Sinchon, Seoul, Republic of Korea. Monitoring was performed applying food baited
      traps for 2 days per week. Reduction rates of German cockroaches by applying
      fipronil baits were 90.9% at Korean restaurants, 96.4% at Chinese restaurants,
      and 89.4% in beer hall kitchens after 4 weeks of the treatment. Overall average
      of the reduction rate was 93.9%. As the natural reduction rate at untreated
      restaurants was 11.5% after 4 weeks, a correction of the average reduction rate
      by applying the Abbot formula was 93.1%.

PMID- 16969065
TI  - Molecular cloning of a rhoptry protein (ROP6) secreted from Toxoplasma gondii.
AB  - Monoclonal antibody (mAb) Tg786 against Toxoplasma gondii has been found to
      detect a 42-kDa rhoptry protein (ROP6) which showed protease activity and host
      cell binding characteristics after secretion. Using the mAb, a colony containing
      a 3o-UTR was probed in a T. gondii cDNA expression library. A full length cDNA
      sequence of the rhoptry protein was completed after 5o-RACE, which consisted of
      1,908 bp with a 1,443 bp ORF. The deduced amino acid sequence of ROP6 consisted
      of a polypeptide of 480 amino acids without significant homology to any other
      known proteins. This sequence contains an amino terminal stop transfer sequence
      downstream of a short neutral sequence, hydrophilic middle sequence, and
      hydrophobic carboxy terminus. It is suggested that the ROP6 is inserted into the
      rhoptry membrane with both N- and C-termini.

PMID- 16969067
TI  - House dust mite fauna in western Anatolia, Turkey.
AB  - House dust mites play an important role in the pathogenesis of allergic diseases.
      Many factors may influence mite growth. The presence of mites is related to mean
      temperature and humidity as well as altitude. The aim of this study was to
      analyze the mite fauna in 5 regions of western Anatolia, Turkey, that have
      similar climatic properties with low mean temperature and humidity, but differ in
      altitude. During the period October-November 2004, house dust was collected from
      290 homes in 5 different cities. House dust mites were isolated in 67 (23.1%) of
      290 samples. The family Pyroglyphidae (Astigmata) was present in all positive
      samples. This study suggests that the selected western Anatolian regions that
      share similar environmental conditions host similar dust mite populations.

PMID- 16969068
TI  - Status of intestinal helminthic infections of borderline residents in North
      Korea.
AB  - The present authors investigated intestinal parasitic infections among North
      Korean residents and refugees in China in 2003. The Kato-Katz method was applied
      to 236 residents and soldiers in a town on the North Korea-China border and to 46
      people at a refugee camp in China. Only eggs of Ascaris and Trichuris were
      detected, with egg positive rates of 41.1% and 37.6%, respectively. The total egg
      positive rate was 55.0% and most of those who were egg positive were only lightly
      infected. Women of 61.2% and men of 53.1% were egg positive. The refugees from
      rural areas showed higher egg positive rates than those from urban areas. The
      present investigation confirmed high prevalence of soil-transmitted intestinal
      helminths in rural borderline areas of North Korea.

PMID- 16969069
TI  - Hypophosphorylation of residue Y1045 leads to defective downregulation of
      EGFRvIII.
AB  - Downregulation of the EGF receptor is the net result of receptor degradation and
      recycling. Cbl functions by specifically targeting activated ErbB receptors for
      ubiquitination, facilitating ligand-induced desensitization of EGFR. The
      interaction between EGFR and c-Cbl has been shown to depend upon receptor
      phosphorylation at tyrosine residue 1045, the major docking site for c-Cbl. To
      better understand the biological consequences of EGFR mutants in human cancers,
      we compared wild-type EGFR and EGFRvIII internalization, as well as gefitinib
      sensitive and resistant EGFR kinase mutations found in non-small cell lung
      carcinoma. We observed that Cbl failed to associate with EGFRvIII as well as an
      inability of the receptor to undergo ubiquitination and degradation. The most
      intriguing observation is that EGFRvIII tyrosine 1045 residue is either un
      phosphorylated or hypophosphorylated. This is in contrast to other tyrosine
      residues in EGFRvIII, such as Y1173, which exhibit levels of phosphorylation
      comparable to those of wild-type EGFR. These results suggest that
      hypophosphorylation of tyrosine residue 1045 is likely to be the cause for
      EGFRvIII escape from c-Cbl-induced ubiquitination and degradation, enhancing
      EGFRvIII's ability to increase proliferation in breast cancer cells.
      Interestingly, inefficient degradation was only observed in the gefitinib
      resistant EGFR kinase mutant, despite the fact that this mutant receptor is
      capable of recruiting c-Cbl and undergoes ubiquitination. The gefitinib sensitive
      EGFR kinase mutant exhibits similar ubiquitination and degradation patterns as
      the wild-type EGFR. Collectively, different EGFR mutations exert various negative
      mechanisms that have the potential to modify receptor internalization and
      degradation, and may play a critical role in resistance to tyrosine kinase
      inhibitory treatments.

PMID- 16969070
TI  - Randomized discontinuation trial of sorafenib (BAY 43-9006).
AB  - With the increasing interest in development of cytostatic anticancer drugs, the
      randomized discontinuation trial (RDT) design has been proved to be useful in the
      evaluation of their clinical activity. In the June 1, 2006 issue of the Journal
      of Clinical Oncology, a study by Ratain et al. uses RDT in a phase-II placebo
      controlled study to evaluate the efficacy of sorafenib (BAY 43-9006) in patients
      with metastatic renal cell carcinoma (RCC). The results from their investigation
      affirm the merits of the RDT in testing the efficacy of cytostatic drugs and also
      prove the significant disease-stabilizing activity and tolerability of sorafenib
      in metastatic renal cell carcinoma.

PMID- 16969071
TI  - Circulating cell-free DNA: a novel biomarker for response to therapy in ovarian
      carcinoma.
AB  - INTRODUCTION: Cell-free DNA (CFDNA) is a reflection of both normal and tumor
      derived DNA released into the circulation through cellular necrosis and
      apoptosis. We sought to determine whether tumor-specific plasma DNA could be used
      as a biomarker for tumor burden and response to therapy in an orthotopic ovarian
      cancer model. METHODS: Female nude mice injected intraperitoneally with HeyA8
      ovarian cancer cells were treated with either docetaxel alone or in combination
      with anti-angiogenic agents (AEE788-dual VEGFR and EGFR antagonist or EA5
      monoclonal antibody against ephrin A2). Following DNA extraction from plasma,
      quantification of tumor-specific DNA was performed by real-time PCR using human
      specific beta-actin primers. The number of genome equivalents (GE/ml) were
      determined from a standard curve. Apoptosis was assessed by TUNEL staining of
      treated tumors. RESULTS: The levels of tumor-specific DNA in plasma increased
      progressively with increasing tumor burden (R2=0.8, p<0.01). Additionally, tumor
      specific plasma DNA levels varied following treatment with chemotherapy. In mice
      with established tumors (19 days following tumor injection), tumor-specific
      plasma DNA levels increased by 63% at 24 hours following a single dose of
      docetaxel (15 mg/kg), and then declined to 20% below baseline at 72 hours and
      were 83% lower than baseline 10 days following therapy. In addition, docetaxel
      treatment resulted in a significant increase in the apoptotic index at 24 hours
      (p<0.01). Moreover, in two separate therapy experiments using a combination of
      cytotoxic chemotherapy with anti-angiogenic agents, tumor-specific plasma DNA
      levels were significantly higher in mice treated with vehicle compared to the
      treatment groups. The correlation between tumor weight and tumor-specific DNA in
      these experiments was 0.71-0.76 (p<0.01). CONCLUSIONS: Our results indicate that
      tumor-specific CFDNA levels correlate with increasing tumor burden and decline
      following therapy. Thus, tumor-specific DNA may be a useful surrogate biomarker
      of therapeutic response and should be evaluated in future clinical trials.

PMID- 16969072
TI  - Important differences between topoisomerase-I and -II targeting agents.

PMID- 16969073
TI  - PV-1 is negatively regulated by VEGF in the lung of caveolin-1, but not caveolin
      2, null mice.
AB  - An N-glycosylated 60-kDa PV-1 protein that binds heparin was detected in mouse
      lung from a single mRNA transcript. In the absence of disulfide bond reduction PV
      1 is detected as a dimer or large molecular weight oligomer. In the lung of Cav
      1, but not Cav-2, null mice the amount of PV-1 protein is diminished, with no
      detectable change in mRNA level. PV-1 does not fractionate with caveolae on a
      sucrose density gradient, but the Cav-1 protein is detected in fractions
      following immunoprecipitation with PV-1 antibodies. Both PV-1 and Cav-1 localize
      to alveolar endothelial cells, but PV-1 is concentrated at the abluminal and Cav
      1 at the luminal cell surface with minimal colocalization. In the Cav-1 null
      lungs, PV-1 is nearly undetectable in endothelial cells, but remains unchanged in
      pneumocytes and bronchial epithelial cells. Injection of a VEGF-R2 inhibitor
      increased PV-1 protein in lung of Cav-1 null, but not Cav-2 or wild-type mice.
      These data indicate that the PV-1 protein is negatively regulated in pulmonary
      endothelial cells by VEGF-R2 signaling.

PMID- 16969074
TI  - Ubiquitination of Myc: flipping the switch.
AB  - Ubiquitination plays a key role in regulating multiple oncoproteins, including
      those of the Myc-family. A recent Cell paper by Adhikary et al reports that a
      novel E3 ligase, HectH9, mediates site-specific ubiquitination of Myc and thereby
      fosters a switch from repression to transcriptional activation. This insight
      elucidates Myc's diverse properties and provides new targets for the development
      of anti-cancer therapy.

PMID- 16969075
TI  - H32, a non-quinone sulfone analog of vitamin K3, inhibits human hepatoma cell
      growth by inhibiting Cdc25 and activating ERK.
AB  - We previously synthesized a K-vitamin derivative, Cpd 5, which was a potent
      growth inhibitor of human tumor cells, including Hep3B hepatoma cells. However,
      being a quinone compound, Cpd 5 has the potential for generating toxic reactive
      oxygen species (ROS). We therefore synthesized a nonquinone sulfone derivative,
      H32, which has a sufone group substituting the quinone. The IC50 of H32 for Hep3B
      cells was found to be 2.5 microM, which was 2.5 and 3.2 times more potent than
      Cpd 5 and vitamin K3 respectively. It induced apoptosis in Hep3B cells but did
      not generate ROS when compared to Cpd 5. Interestingly, under similar culture
      conditions, normal rat hepatocytes were 14-fold more and 7-fold more resistant to
      the growth inhibitory effects of H32 than Hep3B and PLC/PRF5 cells respectively.
      H32 preferentially inhibited the activities of the cell cycle controlling Cdc25A
      phosphatase likely by binding to its catalytic cysteine. As a consequence, it
      induced inhibitory tyrosine phosphorylation of the Cdc25 substrate kinases Cdk2
      and Cdk4 in Hep3B cells and the cells undergo an arrest in the G1 phase of the
      cell cycle. H32 also induced persistent phosphorylation of the MAPK protein
      ERK1/2, but marginal JNK1/2 and p38 phosphorylation. The ERK inhibitor U0126,
      added at least 30 min prior to H32, antagonized the growth inhibition induced by
      H32. However, the JNK and p38 inhibitors, JNKI-II and SB203580, were not able to
      antagonize H32 induced growth inhibition. Thus, H32 differentially inhibited
      growth of normal and liver tumor cells by preferentially inhibiting the actions
      of Cdc25 phosphatases and inducing persistent ERK phosphorylation.

PMID- 16969077
TI  - CD28 costimulation mediates transcription of SKP2 and CKS1, the substrate
      recognition components of SCFSkp2 ubiquitin ligase that leads p27kip1 to
      degradation.
AB  - Activation through TCR/CD3-plus-CD28 induces primary T lymphocytes to enter S
      phase. Downregulation of cyclin-dependent kinase inhibitor p27(kip1) is critical
      in this process and is mediated by ubiquitin-targeted degradation of p27(kip1).
      Ubiquitination of p27(kip1) is performed by the SCF(skp2) ubiquitin ligase
      comprised of the core components Roc1, Cul1 and Skp1 and the substrate
      recognition components Skp2 and Cks1. Here we show that in primary human T
      lymphocytes, the SCF(skp2) core components Roc1, Cul1 and Skp1 are constitutively
      expressed, and their levels remain unchanged upon TCR/CD3-plus-CD28
      costimulation. In contrast, the substrate recognition components Skp2 and Cks1
      are almost undetectable in resting T cells and are transcriptionally induced upon
      costimulation. We determined that the SKP2 promoter lies directly upstream of the
      translational start site and contains binding sites for SP1, Elk-1 and E2F
      transcription factors. Mutagenesis of SP1 and Elk-1 sites abrogated TCR/CD3-plus
      CD28-mediated SKP2 promoter-driven reporter activity, whereas mutagenesis of an
      E2F site enhanced reporter activity, suggesting that SKP2 promoter may act as a
      node of integration for mitogenic and anti-mitogenic signals. Thus, in primary T
      lymphocytes CD28 costimulation can directly regulate cell cycle progression by
      inducing transcription of the substrate recognition components of SCF(skp2)
      ubiquitin ligase that targets p27(kip1) for degradation.

PMID- 16969076
TI  - Recurrent KRAS codon 146 mutations in human colorectal cancer.
AB  - An activating point mutation in codon 12 of the HRAS gene was the first somatic
      point mutation identified in a human cancer and established the role of somatic
      mutations as the common driver of oncogenesis. Since then, there have been over
      11,000 mutations in the three RAS (HRAS, KRAS and NRAS) genes in codons 12, 13
      and 61 reported in the literature. We report here the identification of recurrent
      somatic missense mutations at alanine 146, a highly conserved residue in the
      guanine nucleotide binding domain. In two independent series of colorectal
      cancers from Hong Kong and the United States we detected KRAS A146 mutations in
      7/126 and 2/94 cases, respectively, giving a combined frequency of 4%. We also
      detected KRAS A146 mutations in 2/40 (5%) colorectal cell lines, including the
      NCI-60 colorectal cancer line HCC2998. Codon 146 mutations thus are likely to
      make an equal or greater contribution to colorectal cancer than codon 61
      mutations (4.2% in our combined series, 1% in the literature). Lung
      adenocarcinomas and large cell carcinomas did not show codon 146 mutations. We
      did, however, identify a KRAS A146 mutation in the ML-2 acute myeloid leukemia
      cell line and an NRAS A146 mutation in the NALM-6 B-cell acute lymphoblastic
      leukemia line, suggesting that the contribution of codon 146 mutations is not
      entirely restricted to colorectal cancers or to KRAS.

PMID- 16969078
TI  - PV-1 labels trans-cellular openings in mouse endothelial cells and is negatively
      regulated by VEGF.
AB  - The PV-1 protein is endogenously expressed from a single mRNA in the mouse
      pancreatic MS-1 endothelial cell line as a 60-kDa N-glycosylated and 50-kDa non
      glycosylated protein that form DTT sensitive oligomers. In the absence of cell
      permeabilization, PV-1 antibodies label transcellular openings of variable size,
      many that penetrate through the cytosol with circular openings on the free and
      attached surface of the plasma membrane. Intracellular PV-1 is localized in
      perinuclear aggregates that can extend as a fibrous network through the cytosol
      and often surround the nuclear compartment. In some cells, PV-1 is organized as a
      large unipolar spindle-like structure that is often associated with severe
      deformation of the nucleus. The VEGF-R2 inhibitor SU5614 increased the PV-1
      protein levels in a dose-dependent manner and inhibited MS-1 cell growth, without
      inducing apoptosis. This report provides compelling evidence for a functional
      role of PV-1 in the formation of large transendothelial channels and modulation
      of nuclear shape. Moreover, these data suggest the PV-1 protein is negatively
      regulated by VEGF.

PMID- 16969079
TI  - Lys63-linked polyubiquitin chains: linking more than just ubiquitin.
AB  - Polyubiquitin chains linked through the Lys48 residue of ubiquitin are most
      commonly associated with targeting proteins for proteosomal degradation. In
      contrast, polyubiquitin chains linked through the Lys63 residue of ubiquitin are
      associated with nonproteolytic functions such as signal transduction. The
      mechanism by which Lys63-linked polyubiquitin chains participate in signaling
      cascades has yet to be determined, but two recent publications (Wu et al., Nat
      Cell Bio 2006; 8:398-406 and Ea et al., Mol Cell 2006; 22:245-57) shed light on
      how this distinctive modification functions in NFkappaB activation by TNFalpha.
      Upon stimulation with TNFalpha, RIP1 undergoes Lys63-linked polyubiquitination.
      The polyubiquitin chain on RIP1 is recognized and bound by NEMO, the regulatory
      subunit of the IKK complex, and this binding is essential for NFkappaB activation
      by TNFalpha. Thus, Lys63-linked polyubiquitin chains critically connect
      components of NFkappaB signaling in a highly regulated manner.

PMID- 16969081
TI  - Emerging roles of beta-arrestins.
AB  - Arrestins were originally characterized as structural adaptor proteins which
      modulate the desensitization and trafficking of seven-membrane-spanning
      receptors. From these seminal observations a multitude of novel functions for
      this gene family have arisen. Here we review the recently identified roles for
      beta-arrestin including its nuclear function and roles in development, cellular
      migration, and metastasis.

PMID- 16969080
TI  - Regulation and targeting of Eg5, a mitotic motor protein in blast crisis CML:
      overcoming imatinib resistance.
AB  - Patients with blast crisis (BC) CML frequently become resistant to Imatinib, a
      Bcr-Abl tyrosine kinase-targeting agent. Eg5, a microtubule-associated motor
      protein has been described to be highly expressed in BC CML by microarray
      analysis (Nowicki et al., Oncogene 2003; 22:3952-63). We investigated the
      regulation of Eg5 by Bcr-Abl tyrosine kinase and its potential as a therapeutic
      target in BC CML. Eg5 was highly expressed in all Philadelphia chromosome
      positive (Ph(+)) cell lines and BC CML patient samples. Inhibition of Bcr-Abl by
      Imatinib downregulated Eg5 expression in Imatinib-sensitive KBM5 and HL-60p185
      cells, but not in Imatinib-resistant KBM5-STI571, harboring a T315I mutation, and
      Bcr-Abl-negative HL-60 cells. Blocking Eg5 expression with antisense
      oligonucleotide (Eg5-ASO) or inhibiting its activity with the small-molecule Eg5
      inhibitor, S-trityl-L-cysteine induced G(2)/M cell cycle block and subsequent
      cell death in both Imatinib-sensitive and -resistant cells. Further, Eg5-ASO
      treatment of SCID mice harboring KBM5 cell xenografts significantly prolonged the
      median survival of the animals (p = 0.03). Our findings suggest that Eg5 is
      downstream of and regulated by Bcr-Abl tyrosine kinase in Philadelphia chromosome
      positive cells. Inhibition of Eg5 expression or its activity blocks cell cycle
      progression and induces cell death independent of the cellular response to
      Imatinib. Therefore, Eg5 could be a potential therapeutic target for the
      treatment of BC CML, in particular Imatinib-resistant BC CML.

PMID- 16969082
TI  - Keeping mammalian mutation load in check: regulation of the activity of error
      prone DNA polymerases by p53 and p21.
AB  - To overcome DNA lesions that block replication the cell employs translesion DNA
      synthesis (TLS) polymerases, a group of low fidelity DNA polymerases that have
      the capacity to bypass a wide range of DNA lesions. This TLS process is also
      termed error-prone repair, due to its inherent mutagenic nature. We have recently
      shown that the tumor suppressor p53 and the cell cycle inhibitor p21 are global
      regulators of TLS. When these proteins are missing or nonfunctional, TLS gets out
      of control: its extent increases to very high levels, and its fidelity decreases,
      causing an overall increase in mutation load. This may be explained by the loss
      of selectivity in the bypass of specific DNA lesions by their cognate specialized
      polymerases, such that lesion bypass continues to a maximum, regardless of the
      price paid in increased mutations. The p53 and p21 proteins are also required for
      efficient UV light-induced monoubiquitination of PCNA, which is consistent with a
      model in which this modification of PCNA is necessary but not sufficient for the
      normal activity of TLS. This regulation suggests that TLS evolved in mammals as a
      system that balances gain in survival with a tolerable mutational cost, and that
      disturbing this balance causes a potentially harmful increase in mutations, which
      might play a role in carcinogenesis.

PMID- 16969083
TI  - A novel orthotopic bladder tumor model with predictable localization of a
      solitary tumor.
AB  - An ideal bladder tumor model consists in an orthotopic solitary tumor with a well
      defined localization and stage, as well as unaltered normal mucosa. None of the
      existing models covers all these requirements. We have created a new model,
      suitable for diagnostic and therapeutic purposes. Female Fisher rats were divided
      into different groups according to bladder preconditioning and tumor cell (AY27)
      administration. Generalized desepithelialization was obtained by an intravesical
      instillation of HCl, neutralized by NaOH. Localized desepithelialization of the
      bladder fundus was the result of application of a micro-swab, imbibed with the
      same chemicals. Tumor cells administration was either generalized (intravesical
      instillation) or focal (micro swab). No bladder perforations were observed.
      Generalized desquamation always produced multifocal tumors, whereas focal
      application of HCl/NaOH resulted in solitary tumors of the bladder fundus,
      irrespective of the method of tumor cell administration. Only hyperplasia could
      be detected at day 3. AY27 cells were covered by umbrella cells at day 5 and
      subepithelial AY 27 tumor nests, covered by full thickness epithelium were
      observed day 7.

PMID- 16969084
TI  - Understanding mitochondrial genetic abnormalities in cancer etiology: a
      proteomics approach.

PMID- 16969085
TI  - Checkpoint regulation of replication dynamics in UV-irradiated human cells.
AB  - At any moment during S phase, regions of genomic DNA are in various stages of
      replication (i.e., initiation, chain elongation, and termination). These stages
      may be differentially inhibited after treatment with various carcinogens that
      damage DNA such as UV. We used visualization of active replication units in
      combed DNA fibers, in combination with quantitative analyses of the size
      distributions of nascent DNA, to evaluate the role of S-checkpoint proteins in UV
      induced inhibition of DNA replication. When HeLa cells were exposed to a low
      fluence (1 J/m(2)) of 254 nm UV light (UVC), new initiation events were severely
      inhibited (5-6-fold reduction). A larger fluence of UVC (10 J/m(2)) resulted in
      stronger inhibition of the overall rate of DNA synthesis without decreasing
      further the frequency of replicon initiation events. Incubation of HeLa cells
      with caffeine and knockdown of ATR or Chk1 kinases reversed the UVC-induced
      inhibition of initiation of new replicons. These findings illustrate the
      concordance of data derived from different experimental approaches, thus
      strengthening the evidence that the activation of the intra-S checkpoint by UVC
      is dependent on the ATR and Chk1 kinases.

PMID- 16969086
TI  - The BRCA1 E3 ubiquitin ligase controls centrosome dynamics.
AB  - The breast cancer specific tumor suppressor protein 1, BRCA1, mediates functions
      for all cells to grow. The puzzle of BRCA1 is that its loss is only associated
      with tumors in breast and ovarian epithelial cells. In this focused review, we
      highlight the data linking BRCA1 to the centrosome function, and we suggest that
      the specificity for breast tumors is due to a loss in restraint on centrosome
      function. Amplification of centrosome numbers secondary to loss of BRCA1 can
      drive the cell into the aneuploid state, thus, by this perspective loss of BRCA1
      is a mutator phenotype.

PMID- 16969087
TI  - Analysis of EphA2 expression and mutant p53 in ovarian carcinoma.
AB  - The EphA2 tyrosine kinase receptor is frequently overexpressed in ovarian cancer
      and this feature is predictive of poor clinical outcome. Preclinical
      investigation has also linked EphA2 with p53. In our present study, we examined
      EphA2 and p53 status (both expression and full-length mutation status) in 6
      ovarian cell lines and 79 human ovarian cancers to determine potential
      associations. EphA2 was overexpressed in 80% of ovarian cancer cell lines and in
      75% of clinical specimens. In particular, high levels of EphA2 occurred in 91% of
      tumors with p53 null mutations compared to 68% in tumors with wild-type or
      missense mutations (p=0.027). EphA2 expression did not relate to critical versus
      non-critical site missense p53 mutations or the location of mutations on specific
      p53 exons. We also demonstrated that while EphA2 and p53 can provide independent
      information regarding clinical status, the combination of EphA2 and p53 status
      can predict poor clinical outcome. In particular, the combination of EphA2
      overexpression and p53 null status was associated with decreased overall patient
      survival and related to increased incidence of ascites and distant metastasis.
      Taken together, these data indicate a complex relationship between EphA2 and p53
      that appears to regulate EphA2 expression and clinical outcome.

PMID- 16969088
TI  - New in vivo results support concerns about harmful effects of cortisone drugs in
      the treatment of breast cancer.

PMID- 16969089
TI  - Cyclin A1/Cdk2 is sufficient but not required for the induction of apoptosis in
      early Xenopus laevis embryos.
AB  - The role of cyclin-dependent kinases in cell proliferation is well characterized,
      whereas their somewhat paradoxical role in catalyzing apoptosis is less
      understood. One Cdk complex implicated in both cell proliferation and cell death
      is cyclin A/Cdk2. During early embryonic development of Xenopus laevis, distinct
      isoforms of cyclin A are expressed at different times. From fertilization through
      gastrulation, cyclin A1 is the predominant isoform. Cyclin A1 primarily dimerizes
      with Cdk2 but not Cdk1. In contrast, cyclin A2 is expressed at a low level until
      gastrulation, when it becomes the major A-type cyclin and associates with both
      Cdk1 and Cdk2. When Xenopus embryos are treated with ionizing radiation (IR)
      prior to the midblastula transition (MBT), cyclin A1 protein persists beyond the
      MBT and forms an active complex with Cdk2. During this window of cyclin A1/Cdk2
      activity, the embryo undergoes apoptosis. To test the hypothesis that cyclin A1
      associated activity is a mediator of apoptosis, cyclin A1 protein level and
      associated kinase activity were measured in embryos treated with aphidicolin to
      induce apoptosis. Both cyclin A1 content and associated kinase activity were
      sustained after the MBT as embryos underwent apoptosis. To determine whether
      cyclin A1/Cdk2 was sufficient to induce apoptosis, recombinant cyclin A1/Cdk2
      complex was injected into single-celled embryos, which induced apoptosis after
      the MBT. However, morpholinos targeting translation of cyclins A1 and A2 did not
      block apoptosis in embryos treated with X-rays or aphidicolin. These data
      indicate that cyclin A1/Cdk2 is sufficient, but not required for apoptosis during
      early development.

PMID- 16969090
TI  - Histone phosphorylation and pericentromeric histone modifications in oocyte
      meiosis.
AB  - Epigenetic regulation of pericentromeric heterochromatin is crucial for proper
      interactions between kinetochores and spindle microtubules governing accurate
      chromosome segregation. Here, we first examined the dynamic distribution of
      phosphorylated serine 10 and 28 on H3 during mouse oocyte maturation and early
      embryo development using immunofluorescent staining and confocal microscopy. Our
      results revealed strong signals of phosphorylated H3/ser10 and 28 in the
      pericentromeric heterochromatin area and continuous persistent staining of the
      chromosome periphery, respectively. A panel of specific antibodies against
      various acetylated lysine, dimethylated lysine or phosphorylated serine residues
      on histone H3 or H4 were used to investigate the effects of Trichostatin A (TSA),
      a general inhibitor of histone deacetylases (HDACs), on histone modifications of
      pericentromeric heterochromatin. Unexpectedly, TSA treatment was unable to alter
      the acetylation and methylation status of pericentromeric heterochromatin,
      however, it resulted in significant dephosphorylation of H3/ser10 at this site
      during mouse oocyte meiosis, which is likely to play a role in the TSA-induced
      defective chromosome segregation. Furthermore, by using ZM447439, an inhibitor of
      Aurora kinases, we revealed that Aurora kinases may participate in the regulation
      of histone phosphorylation during mouse oocyte maturation.

PMID- 16969091
TI  - Resistance from the flanks: a role for telomere repeat factor 2 in
      chemotherapeutic drug resistance.

PMID- 16969092
TI  - E1B55K-deleted adenovirus (ONYX-015) overrides G1/S and G2/M checkpoints and
      causes mitotic catastrophe and endoreduplication in p53-proficient normal cells.
AB  - In order to take advantage of cell replication machinery, viruses have evolved
      complex strategies to override cell cycle checkpoints and force host cells into S
      phase. To do so, virus products must interfere not only with the basal cell cycle
      regulators, such as pRb or Mad2, but also with the main surveillance pathways
      such as those controlled by p53 and ATM. Recently, a number of defective viruses
      has been produced which, lacking the latter ability, are incapable of replicating
      in normal cells but should be able to grow and finally lyse those cells that,
      such as the tumor cells, have lost their surveillance mechanisms. A prototype of
      these oncolytic viruses is the E1B55K-defective Adenovirus ONYX-015, which was
      predicted to selectively replicate and kill p53-deficient cancer cells. We found
      that, despite wt p53 and notwithstanding the activation of the checkpoint
      regulators p53, ATM and Mad2, ONYX-015 actively replicated in HUVEC cells.
      Furthermore, ONYX-015 replication induced a specific phenotype, which is distinct
      from that of the E4-deleted adenovirus dlE4 Ad5, although both viruses express
      the main regulatory region E1A. This phenotype includes overriding of the G(1)/S
      and G(2)/M checkpoints, over-expression of MAD2 and retardation of mitosis and
      accumulation of polyploid cells, suggesting the occurrence of alterations at the
      mitotic-spindle checkpoint and impairment of the post-mitotic checkpoint. Our
      data suggest that viral E1A and E4 region products can override all host cell
      checkpoint response even at the presence of a full activation of the ATM/p53
      pathway. Furthermore, the E4 region alone seems to act independently of the
      E1B55K virus product in impairing the ATM-dependent, p53-independent G(2)/M
      checkpoint since dlE4 Ad5-infected cells arrested in G(2) while ONYX-015-infected
      cells did enter mitosis.

PMID- 16969093
TI  - Before and after the spindle assembly checkpoint--an APC/C point of view.
AB  - On May 17-21, 2006 the Cold Spring Harbor Laboratory meeting on the cell cycle
      reunited over 350 researchers to discuss new findings in the cell cycle field. A
      common thread that connected numerous presentations was the regulation of the
      anaphase promoting complex/cyclosome (APC/C). This was also the main theme of the
      lecture given by the keynote speaker, Marc Kirschner (Harvard), who talked about
      "The unexpected importance of UbcH10 in both the G(1)/S transition and the
      initiation of anaphase", and it is also the main focus in this summary.

PMID- 16969094
TI  - Mcl-1 is a relevant molecular target for antisense oligonucleotide strategies in
      gastric cancer cells.
AB  - Gastric cancer is the second most common cause of death from cancer worldwide and
      resistant to various chemotherapeutic regimens. In gastric cancer, the anti
      apoptotic Mcl-1 protein is expressed in up to 75% of all cases and associated
      with poor prognosis. The biological relevance of Mcl-1 expression in gastric
      cancer is unclear. Thus, we investigated the functional significance and
      potential role of Mcl-1 as a molecular target in gastric cancer by using an
      antisense strategy. Gastric cancer cell lines (NCI-N87, MKN-28, MKN-45) were
      treated with Mcl-1 antisense oligonucleotides. Protein expression, cell growth
      and apoptosis were assessed for single-agent Mcl-1 AS oligonucleotide treatment
      and for combinations with docetaxel or cisplatin. Treatment by Mcl-1 AS
      oligonucleotides resulted in approximately 50% reduction in Mcl-1 protein levels
      in all gastric cancer cell lines examined. Surprisingly, dose-dependent Mcl-1
      downregulation produced a significant increase in apoptosis and up to 60%
      decrease in cell growth. Moreover, combination of Mcl-1 AS oligonucleotide with
      docetaxel or cisplatin displayed synergistic anti-tumor activity. In conclusion,
      the impressive single-agent anti-tumor activity and the synergistic effect of Mcl
      1 AS oligonucleotides in combination with chemotherapy might qualify Mcl-1 as a
      promising molecular target for AS oligonucleotide based treatment strategies for
      gastric cancer in the future.

PMID- 16969095
TI  - Lysyl oxidase (LOX) and hypoxia-induced metastases.
AB  - Angiogenesis is a critical process in the transition of tumors from a localized,
      primary site to a distant site of metastases. Hypoxic conditions within the tumor
      mass lead to the activation of signalling pathways which initiate tumor cell
      invasion, migration, adhesion and subsequent angiogenesis. Several key molecular
      players in hypoxia-induced tumor progression are well-described, e.g., hypoxia
      inducible factor-1 (HIF-1) and angiopoietin-2; however, drug development aimed at
      suppressing individual members of this signalling cascade has proven to be
      challenging. The article by Erler et al. published in Nature (Vol. 440, April
      2006) identifies lysyl oxidase (LOX) as an essential enzyme for hypoxia-induced
      metastases. This Journal Club reviews the findings presented by Erler and
      colleagues and briefly discusses the implications of LOX in cancer.

PMID- 16969096
TI  - Synphilin isoforms and the search for a cellular model of lewy body formation in
      Parkinson's disease.
AB  - A common finding in many neurodegenerative diseases is the presence of inclusion
      bodies made of aggregated proteins in neurons of affected brain regions. In
      Parkinson's disease, the inclusion bodies are referred to as Lewy bodies and
      their main component is alpha-synuclein. Although many studies have suggested
      that inclusion bodies may be cell protective, it is still not clear whether Lewy
      bodies promote or inhibit dopaminergic cell death in Parkinson's disease.
      Synphilin-1 interacts with alpha-synuclein and is present in Lewy bodies.
      Accumulation of ubiquitylated synphilin-1 leads to massive formation of inclusion
      bodies, which resemble Lewy bodies by their ability to recruit alpha-synuclein.
      We have recently isolated an isoform of synphilin-1, synphilin-1A, that
      spontaneously aggregates in cells, and is present in detergent-insoluble
      fractions of brain protein samples from alpha-synucleinopathy patients. Synphilin
      1A displays marked neuronal toxicity and, upon proteasome inhibition, accumulates
      into ubiquitylated inclusions with concomitant reduction of its intrinsic
      toxicity. The fact that alpha-synuclein interacts with synphilin-1A, and is
      recruited to synphilin-1A inclusion bodies in neurons together with synphilin-1,
      further indicates that synphilin-1A cell model is relevant for research on
      Parkinson's disease. Synphilin-1A cell model may help provide important insights
      regarding the role of inclusion bodies in Parkinson's disease and other
      neurodegenerative disorders.

PMID- 16969097
TI  - Calmodulin-mediated cell cycle regulation: new mechanisms for old observations.
AB  - The significance of divalent calcium ions (Ca(2+)) to cell cycle progression has
      been a subject of study for several decades, with a regulatory role for Ca(2+)
      suggested in distinct cell types and multiple organisms. Our interest in
      proliferative vascular diseases led us to focus on mammalian vascular smooth
      muscle cells (VSMC) in particular, in which we and others had shown that a
      coordinate elevation in the intracellular free Ca(2+) concentration is required
      for G(1) to S phase cell cycle progression. However, the molecular basis for this
      Ca(2+)-sensitive cell cycle transition was not known. Our recent discovery of a
      functional protein-protein interaction between the late G1-active cyclin E1 and
      the major calcium signal-transducing factor calmodulin (CaM) sheds new light on
      the mechanism(s) through which Ca2+ concentrations regulate cell cycle. Having
      identified a CaM-binding site on cyclin E1, our studies support a direct role for
      CaM in mediating Ca2+-sensitive cyclin E/CDK2 activity and G1 to S phase
      transitions in VSMC. The CaM binding site identified on cyclin E1 has a Kd for
      CaM consistent with that of known CaM-binding proteins, and is composed of a 22
      amino acids N-terminal sequence that is highly conserved across several mammalian
      species. Deletion of this binding site abolished CaM binding and Ca2+-sensitive
      cyclin E/Cdk2 activity. Here we provide our perspectives on the literature
      supporting a role for Ca2+ in cell cycle regulation, focusing on the evidence
      implicating CaM in this functionality, and discuss the potential for therapeutic
      modulation of CaM-dependent cell cycle machinery.

PMID- 16969099
TI  - The role of N-cadherin, MCAM and beta3 integrin in melanoma progression,
      proliferation, migration and invasion.
AB  - Melanoma, the most aggressive form of skin cancer, which accounts for 75% of all
      skin cancer-related deaths, continues to rise at an alarming rate worldwide.
      Despite a favorable cure rate when surgically removed at an early stage, the
      response rate of patients with metastatic disease to single agent chemotherapy is
      less than 15%, and biologic therapies are only marginally effective. Given this
      bleak picture, there is a great need to identify and characterize genes that play
      an important role in the advanced stages of melanoma and thus, may represent
      valuable targets for clinical therapy. The cell adhesion molecules N-cadherin,
      MCAM and beta3 integrin have been suggested to represent melanoma progression
      markers; yet, little is known as to whether they may constitute therapeutic
      targets for the disease. To provide information regarding this aspect, we
      determined by way of whole-genome and tissue microarray analysis, their level of
      expression concordant with melanoma progression, and via RNA interference and
      antisense technology, their role in melanoma cell proliferation, migration, and
      invasion. The results of these studies demonstrate that N-cadherin and beta3
      integrin expression correlates with progression to advanced-stage melanoma,
      whereas expression of MCAM does not. On the other hand, MCAM and beta3 integrin
      are the two adhesion molecules that play a pivotal role in melanoma cell
      migration and invasion, and for this reason, may represent valuable targets for
      melanoma therapy.

PMID- 16969098
TI  - Critical role of the HMGA2 gene in pituitary adenomas.
AB  - The molecular pathway leading to pituitary tumorigenesis is still largely unknown
      and is one of the challenges of the endocrine oncology. The development of
      pituitary adenomas in HMGA2 transgenic mice and the finding of HMGA2
      amplification and overexpression in human pituitary adenomas led us to
      investigate the mechanism by which the HMGA2 gene plays a crucial role in
      pituitary oncogenesis. This mechanism has been recently described by our group:
      it entails the acetylation of E2F1, and its consequent enhanced activity,
      following the displacement of HDAC1 from the pRB/E2F1 inhibitory complex. Based
      on the mating between HMGA2 transgenic and E2F1 knockout mice, the activation of
      E2F1 appears to be the main mechanism of the onset of HMGA2-induced pituitary
      adenoma development. Nevertheless, other events may be also involved in this
      process, and are discussed here.

PMID- 16969100
TI  - Proliferation: the most prominent predictor of clinical outcome in breast cancer.
AB  - We recently identified a gene expression cassette of 97 unique genes that were
      consistently differentially expressed between low and high grade breast
      carcinomas. The majority of these genes were overexpressed in high grade tumors
      and, as expected, they were associated with cell cycle progression and
      proliferation. Interestingly, by applying this gene expression cassette to
      several datasets, we demonstrated that intermediate grade tumors were composed of
      a mixture of well- and poorly- differentiated tumors with statistically distinct
      clinical outcome similar to those of low and high grade carcinomas. Furthermore,
      these proliferation-related genes appear to be a common denominator of several
      existing prognostic gene expression signatures. This recapitulates their
      prognostic power far beyond the estrogen receptor (ER) status and highlights the
      importance of proliferation genes in breast cancer biology. Importantly, their
      weight seems to be far more important in ER-positive than in ER-negative disease.

PMID- 16969101
TI  - CIN By WNT: growth pathways, mitotic control and chromosomal instability in
      cancer.
AB  - There is mounting evidence suggesting that an instable genome is directly
      involved in the development of cancer. The predominant form of genomic
      instability in most cancers presents itself as an increased rate of loss or gain
      in chromosome number and parts, referred to as chromosomal instability (CIN).
      Indeed, mutations in components of mitotic checkpoints have been described in
      human cancers, albeit in low numbers, suggesting that although CIN principally
      arises due to defective surveillance of mitosis, its molecular causes remain
      largely unclear. We have recently shown that the Wnt/beta-catenin signaling
      pathway, whose aberrant activation has been established as the driving force of
      tumorigenesis in many cancers particularly colorectal cancer, can generate CIN
      through the transcriptional target gene conductin/axin2. Here we propose a model
      for the generation of CIN by aberrant Wnt/beta-catenin signaling and we suggest
      that growth pathways not only control cell cycle progression through G(1)/S
      transition but have also evolved cross talks to regulate mitosis. We speculate
      that aberrant activation of these pathways, as observed in cancer can result in
      chromosomal instability thus explaining the widespread appearance of CIN in human
      cancers.

PMID- 16969102
TI  - Caveolae internalization regulates integrin-dependent signaling pathways.
AB  - Integrin-mediated adhesion regulates trafficking of cholesterol-enriched membrane
      microdomains (CEMM). Upon cell detachment from the extracellular matrix (ECM),
      CEMMs undergo rapid internalization and are cleared from the plasma membrane.
      This pathway regulates integrin-mediated Rac membrane targeting, allowing
      coupling of Rac to downstream effectors. Internalization of CEMMs is mediated by
      Dynamin-2, a regulator of caveolae dynamics, and caveolin-1, an essential
      caveolae coat protein. Translocation of tyrosine phosphorylated caveolin-1 from
      focal adhesions to caveolae upon cell detachment induces CEMM internalization.
      Notably, integrin-mediated regulation of Erk, phosphatidylinositol-3-OH kinase
      (PI3K) and Rac pathways is dependent on caveolin-1. These results describe a
      novel pathway in which integrins prevent downregulation of Erk, PI3K and Rac
      dependent pathways by inhibiting caveolin-1-dependent endocytosis. This pathway
      define a novel molecular mechanism for regulated cell growth and tumor
      suppression by caveolin-1.

PMID- 16969103
TI  - New insights regarding vessel regression.
AB  - The regression of blood vessels is an intrinsic feature of both physiological and
      pathological processes. This suggests the existence of molecular regulators of
      regression, which would be potential targets for management and therapy of
      numerous diseases involving angiogenesis. This review summarizes some of the
      prevailing views on vessel regression and highlights our recent contribution to
      the field.

PMID- 16969104
TI  - Evidence that the ATR/Chk1 pathway maintains normal replication fork progression
      during unperturbed S phase.
AB  - If cells are treated with DNA damaging agents or inhibitors that interfere with
      ongoing DNA replication, the intra-S and S/M checkpoints delay progression
      through S phase and mitotic entry, respectively, to allow time for DNA repair and
      replication restart. In vertebrates, these checkpoint responses to replication
      blocks are largely mediated by the sensor kinase ATR and its major downstream
      effector kinase Chk1. Increasing evidence suggests that the ATR pathway is also
      vital in the absence of exogenous stresses, i.e., during "unperturbed"
      replication. Both ATR and Chk1 are essential proteins in vertebrates, and lack of
      components of the ATR/Chk1 pathway can result in impaired replication and
      spontaneous DNA damage. Here we give an overview of how the ATR/Chk1 pathway
      responds to exogenously blocked replication and then describe evidence for roles
      of this pathway during replication in an unperturbed S phase.

PMID- 16969105
TI  - Histone modifications and the chromatin scaffold for meiotic chromosome
      architecture.
AB  - Chromosomes are capable of remarkable structural adaptability that enables their
      diverse functions. Histone modifications play pivotal roles in conferring
      structural diversity to chromosomes by influencing the compactness of chromatin.
      Several multi-protein complexes bind to chromatin and affect chromosome dynamics,
      including cohesin, condensin, the chromosome passenger complex, and the
      synaptonemal complex. The roles of these complexes in promoting chromosome
      functions include cohesion, condensation and synapsis. It is now crucial to
      define the relationship between the protein complexes that affect chromosome
      architecture and the underlying state of the chromatin. During meiosis
      chromosomes undergo striking morphological changes, including alignment of
      homologous chromosomes, double-strand break formation and repair, and
      establishment of meiosis-specific chromosome structures. These dynamic chromosome
      arrangements are accompanied by the recruitment and expulsion of multi-protein
      complexes from chromatin. Meiotic chromosome dynamics ensure proper chromosome
      segregation and production of healthy gametes. Meiosis thus affords an excellent
      opportunity to determine how histone modifications impact higher order chromosome
      dynamics by affecting localization and function of chromosome protein complexes.
      A meiotic mutation in the Drosophila histone kinase, NHK-1, uncovered a critical
      requirement for histone modifications in chromosome architecture, underscoring
      the power of this approach.

PMID- 16969106
TI  - Oligomerization of p53 precedes its association with dynein and nuclear
      accumulation.
AB  - Previous studies have identified several proteins that associate with
      microtubules and the dynein motor complex including p53, the glucocorticoid and
      the vitamin D receptors, and the APC (adenomatous polyposis coli) protein; but
      neither the residues important for this interaction nor the physical state of the
      proteins involved have been clarified. We observed in SN12C cells harboring a
      mutant p53 truncated at amino acid 336, impaired nuclear localization and
      impaired association with dynein. This finding was confirmed and extended by
      examining a series of truncated p53 proteins that identified residues 336 to 348
      as crucial for association with dynein and nuclear transport. Point mutations
      identified the importance of residues involved in p53 oligomerization in this
      process, establishing a p53 oligomer as the cargo for dynein transport. The
      association of cytosolic p53 oligomers with dynein occurs independent of
      microtubules indicating that following this association, the p53/dynein complex
      then associates with microtubules and is transported to the peri-nuclear region.
      These studies suggest that mutations or modifications that affect p53
      oligomerization not only interfere with DNA binding but also with its
      intracellular distribution. They also highlight the importance of an intact
      microtubule network in the trafficking of crucial cellular proteins.

PMID- 16969107
TI  - EGFR targeted therapy: view from biological standpoint.
AB  - Activating mutations in the kinase domain of the epidermal growth factor receptor
      (EGFR) in nonsmall cell lung cancers (NSCLCs) correlate with responsiveness to
      EGFR kinase inhibitors. In vitro cell culture studies have demonstrated that EGFR
      kinase domain mutants but not wild type (wt) EGFR are transforming and essential
      for cancer cell survival. We and others have recently demonstrated that the
      induction of EGFR kinase domain mutants specifically in murine lung epithelium in
      vivo led to development of adenocarcinoma with bronchioloalveolar carcinoma (BAC)
      features. These tumors depend completely on the sustained expression of EGFR
      kinase domain mutants for tumor maintenance. The murine tumors with EGFR kinase
      domain mutations are sensitive to EGFR targeted therapy similarly to NSCLC
      patients whose tumors harbor EGFR mutations. In contrast, initial results suggest
      that overexpression of wt EGFR in murine lungs does not seem to be transforming.
      We therefore divide EGFR targeted therapy in NSCLC patients into two parts: "EGFR
      mutant targeted therapy" and "wt EGFR targeted therapy". The "EGFR mutant
      targeted therapy" targets the oncogene essential for tumor initiation and
      maintenance and is frequently correlated with effective clinical outcome. In
      contrast, "wt EGFR targeted therapy" likely targets the proto-oncogene product wt
      EGFR, which is not directly involved in tumor initiation and maintenance, and in
      these cases, the response has been considerably less dramatic.

PMID- 16969108
TI  - ASPP2: a gene that controls life and death in vivo.
AB  - The fundamental role of apoptosis in tumor prevention and the important role of
      p53 in this process are now universally recognized. Recently, several families of
      p53-binding proteins have been shown to influence p53's decision to direct the
      cells either into the apoptotic pathway or in cell cycle arrest. Among them, the
      ASPP family specifically regulate p53-dependent apoptosis. Its member ASPP2 was
      discovered more than 10 years ago as a binding partner of p53 and its role as a
      positive regulator of p53 mediated apoptosis has been clearly established in
      vitro. However, its physiological importance in vivo has just emerged through the
      generation and characterisation of the ASPP2-deficient mice. We now know that
      ASPP2 is a haploinsufficient tumor suppressor and an important activator of p53
      during mouse development and tumor suppression in vivo. ASPP2 might be a novel
      target for future cancer therapy.

PMID- 16969109
TI  - Initiation of chromosomal DNA replication in mammalian cell-free systems.
AB  - Chromosomal DNA replication is a fundamental part of the cell division cycle of
      eukaryotes, and its disruption often leads to genome instability and cancer. A
      focus for regulation is the initiation of the first replication forks, marking
      the transition from G1 to S phase. Direct biochemical investigation of the
      establishment and further progression of chromosomal DNA replication in human
      somatic cell nuclei has become possible through a cell-free system that obeys
      cell cycle control. Since its development less than a decade ago, several
      modifications and adaptations of the original system have been reported, which
      have led to temporal resolution of replication complex assembly and to the
      identification of novel DNA replication factors. Here, I will review the
      different systems, highlight fundamental differences and unifying concepts, and
      discuss their potential for understanding chromosomal DNA replication in somatic
      mammalian cells.

PMID- 16969111
TI  - Targeting cyclins and cyclin-dependent kinases in cancer: lessons from mice,
      hopes for therapeutic applications in human.
AB  - The activity of cyclins and their associated cyclin-dependent kinases (CDKs) is
      frequently deranged in human cancers. For this reason, cyclin-CDK complexes have
      been considered as very promising therapeutic targets in human malignancies. An
      obvious concern, however, is whether blocking cyclin-CDK function would
      preferentially affect cancer cells, but not normal, non-transformed cells. Two
      recent reports addressed the requirement for cyclin D1-CDK4 kinase in mouse
      development versus in neoplasia. These studies documented that the kinase
      activity of cyclin D1-CDK complexes is largely dispensable for normal
      development, but it is critically required for the initiation and maintenance of
      mammary carcinomas. Here we summarize the lessons learned from mouse knockout
      experiments, and discuss the utility of CDK inhibitors in therapy of human
      cancers, and possibly of other diseases.

PMID- 16969110
TI  - Condensin function in mitotic nucleolar segregation is regulated by rDNA
      transcription.
AB  - Chromosome condensation is established and maintained by the condensin complex.
      The mechanisms governing loading of condensin onto specific chromosomal sites
      remain unknown. To elucidate the molecular pathways that determine condensin
      binding to the nucleolar organizer, a key condensin binding site, we analyzed the
      properties of condensin-bound sites within the rDNA repeat in budding yeast and
      demonstrated that the bulk of mitotic condensin binding to rDNA is reduced or
      eliminated when Pol I transcription is elevated. Conversely, when Pol I
      transcription is repressed either by rapamycin treatment or by promoter shut-off,
      condensin binding to rDNA is increased. This novel potential role for
      constitutive and/or periodic repression of Pol I transcription in rDNA condensin
      loading is an important factor in determining the segregation proficiency of NOR
      containing chromosomes.

PMID- 16969112
TI  - Identification of target genes in their native cellular context: an analysis of
      EWS/FLI in Ewing's sarcoma.
AB  - Ewing's sarcoma is the second most common tumor of bone in children and young
      adults, and requires highly intensive chemotherapy along with surgery and/or
      radiation for successful treatment. Because these therapies are associated with
      significant short- and long-term side effects, new therapeutic approaches are
      needed. Most cases of Ewing's sarcoma contain somatic translocations between
      chromosomes 11 and 22 that result in the t(11;22)(q24;q12). This translocation
      encodes the EWS/FLI fusion protein. EWS/FLI formation appears to be the critical
      oncogenic event in the development of Ewing's sarcoma. It is hoped that an in
      depth understanding of the mechanism that EWS/FLI uses to cause oncogenic
      transformation will result in new therapies for this disease. Unfortunately, this
      hope has not been realized. One difficulty has been the lack of an appropriate
      model system in which to study the fusion oncoprotein. We recently described and
      validated the use of retroviral RNA interference approaches to study EWS/FLI in
      Ewing's sarcoma cell lines. We now put this model into a historical context, and
      describe the benefits (both perceived and observed) of this model over previous
      approaches using heterologous cell types.

PMID- 16969113
TI  - The positive regulation of p53 by the tumor suppressor VHL.
AB  - The ubiquitin-mediated degradation of hypoxia-inducible factor-alpha (HIF-alpha)
      by a von Hippel-Lindau tumor suppressor protein (pVHL) is mechanistically
      responsible for controlling gene expression due to oxygen availability. Germline
      mutations in the VHL gene cause dysregulation of HIF and induce an autosomal
      dominant cancer syndrome referred to as VHL disease. However, it is unclear
      whether HIF accumulation caused by VHL mutations is sufficient for tumorigenesis.
      Recently, we found that pVHL directly associates and positively regulates the
      tumor suppressor p53 by inhibiting Mdm2-mediated ubiquitination, and by
      subsequently recruiting p53-modifying enzymes. Moreover, VHL-deleted RCC cells
      showed attenuated apoptosis or abnormal cell-cycle arrest upon DNA damage, but
      became normal when pVHL was restored. Thus, pVHL appears to play a pivotal role
      in tumor suppression by participating actively as a component of p53
      transactivation complex during DNA damage response.

PMID- 16969114
TI  - Functional interaction of CREB binding protein (CBP) with nuclear transport
      proteins and modulation by HDAC inhibitors.
AB  - Nuclear transport proteins such as CSE1, NUP93 and Importin-alpha have recently
      been shown to be chromatin-associated proteins in yeast, which have unexpected
      functions in gene regulation. Here we report interactions between the mammalian
      histone acetyltransferase CBP with nuclear transport proteins CAS (a CSE1
      homologue) and Importin-alpha (Impalpha) and NUP93. CAS was found to bind the
      SRC1 interaction domain (SID) of CBP via a leucine-rich motif in the N-terminus
      of the protein, that is conserved in other SID-binding proteins.
      Coimmunoprecipitation experiments also revealed that CBP and Impalpha proteins
      form a complex. As Impalpha is a known acetylation target of CBP/p300, and is
      recycled to the cytoplasm via the exportin CAS, we investigated whether HDAC
      inhibitors would alter the subcellular localization of these proteins. Treatment
      of COS-1 cells with the HDAC inhibitors trichostatin A or sodium butyrate
      resulted in sequestration of Impalpha in the nuclear envelope, accumulation of
      CAS in nuclear aggregates, and an increased number of CBP-containing PML bodies
      per cell. In addition, HDACi treatment appeared to enhance the association of
      Impalpha and CBP in coimmunoprecipitation experiments. Our results provide
      evidence for novel functional interactions between the chromatin modification
      enzyme CBP and nuclear transport proteins in mammalian cells.

PMID- 16969115
TI  - Replication-dependent DNA damage response triggered by roscovitine induces an
      uncoupling of DNA replication proteins.
AB  - The cyclin-dependent kinase (CDK) inhibitor roscovitine is under evaluation in
      clinical trials for its antiproliferative properties. Roscovitine arrests cell
      cycle progression in G(1) and in G(2) phase by inhibiting CDK2 and CDK1, and
      possibly CDK7 and CDK9. However, the effects of CDK2 inhibition in S-phase cells
      have been not fully investigated. Here, we show that a short-term treatment with
      roscovitine is sufficient to inhibit DNA synthesis, and to activate a DNA damage
      checkpoint response, as indicated by phosphorylation of p53-Ser15, replication
      protein A, and histone H2AX. Analysis of DNA replication proteins loaded onto DNA
      during S phase showed that the amount of proliferating cell nuclear antigen
      (PCNA), a cofactor of DNA replication enzymes, was significantly reduced by
      roscovitine. In contrast, chromatin-bound levels of DNA polymerase delta, DNA
      ligase I and CDK2, were stabilized. Checkpoint inhibition with caffeine could
      rescue PCNA disassembly only partially, pointing to additional effects due to
      CDK2 inhibition and the presence of replication stress. These results suggest
      that in S-phase cells, roscovitine induces checkpoint-dependent and -independent
      effects, leading to stabilization of replication forks and an uncoupling between
      PCNA and PCNA-interacting proteins.

PMID- 16969116
TI  - Redox control of cell cycle progression via Cdc25 phosphatase (Mih1p) in S.
      cerevisiae.

PMID- 16969117
TI  - Bub1 prevents chromosome misalignment and precocious anaphase during mouse oocyte
      meiosis.
AB  - In mitosis the checkpoint proteins ensure faithful chromosome segregation by
      delaying onset of anaphase until all sister chromatids align at the metaphase
      plate of the bipolar spindle correctly. In the present study we blocked the
      function of Bub1 during meiosis by microinjecting anti-Bub1 specific antibody
      into cytoplasm of mouse oocytes, and found that depletion of Bub1 induced evident
      cyclin B degradation and precocious anaphase onset. Bub1 suppression also
      overrode the checkpoint-dependent cell cycle arrest provoked by a low dosage of
      nocodazole. Furthermore, Bub1 depletion induced a significantly higher percentage
      of oocytes with misaligned chromosomes. In addition, we depicted the localization
      dynamics of Bub1 in response to spindle damage and its relationship with
      microtubules and chromosomes, providing further evidence for Bub1's role as a
      spindle checkpoint protein. Our data suggest that Bub1 is a critical spindle
      checkpoint protein that regulates accurate chromosome alignment and homolog
      disjunction in mammalian oocyte meiosis.

PMID- 16969118
TI  - Treatment strategies for skeletal complications of cancer.
AB  - Skeletal complications are a common result of many cancers, particularly of
      multiple myeloma and bone metastases of solid tumors originating in the breast,
      prostate or lung. A number of treatment options are available, including
      radiotherapy, radiopharmaceuticals, surgery and chemotherapy. Recently,
      bisphosphonates have emerged as a promising new treatment option for bone
      complications of cancer. These agents are potent inhibitors of osteoclast
      activity that bind to the bone matrix, are released during bone resorption, and
      are subsequently internalized by osteoclasts, where they interfere with
      biochemical pathways and induce osteoclast apoptosis. Bisphosphonates also
      antagonize osteoclastogenesis and promote the differentiation of osteoblasts. As
      a result, bisphosphonates inhibit tumor-induced osteolysis and reduce skeletal
      morbidity. Bisphosphonates are generally well tolerated, although they have
      recently been associated with osteonecrosis of the jaw, a painful and
      debilitating side effect that is only beginning to be understood. Despite this
      concern, bisphosphonates are an important tool in the management of skeletal
      complications of cancer, providing benefits for the treatment of hypercalcemia,
      osteolytic lesions and fractures, as well as offering amelioration of pain and
      improvement in quality of life.

PMID- 16969119
TI  - Bone complications in multiple myeloma.
AB  - Multiple myeloma is the malignant proliferation of plasma cells involving more
      than 10% of the bone marrow. The bone complications associated with multiple
      myeloma include bone pain, pathologic fractures, hypercalcemia of malignancy and
      cord compressions. The principal pathophysiology of bone disease in multiple
      myeloma is a shift in the balance of bone remodeling toward bone resorption. In
      recent years, bisphosphonates have become an important treatment for the bone
      complications of multiple myeloma. Potent inhibitors of osteoclast activity,
      bisphosphonates interfere with biochemical pathways and induce osteoclast
      apoptosis. Bisphosphonates also antagonize osteoclastogenesis and promote
      differentiation of osteoblasts, as well as inhibiting other aspects of osteoclast
      homeostasis and metabolism. Several studies have evaluated treatment with
      bisphosphonates in patients with multiple myeloma, and have demonstrated the
      efficacy of clodronate (Bonefos; Anthra Pharmaceuticals; Princeton, NJ;
      www.bonefos.com), pamidronate (Aredia; Novartis Pharmaceuticals Corp; East
      Hanover, NJ; www.pamidronate.com) and zoledronic acid (Zometa; Novartis
      Pharmaceuticals Corp; East Hanover, NJ; www.us.zometa.com) in reduction of pain,
      reduction of SREs and survival. Moreover, recent data suggest direct and indirect
      antimyeloma activity of pamidronate and zoledronic acid.

PMID- 16969120
TI  - Managing bone complications of solid tumors.
AB  - Bone metastases are a common occurrence in patients with breast cancer, lung
      cancer and prostate cancer. Bone metastases cause considerable morbidity
      including pain, impaired mobility, pathologic fracture, spinal cord or nerve root
      compression, bone marrow infiltration and hypercalcemia of malignancy. These
      complications result from the derangement of normal bone metabolism that arise
      from interactions between factors originating in tumor cells and others
      originating in the microenvironment of the bone. Fortunately, there is an
      increasing array of treatment options for the skeletal complications associated
      with bone metastases arising from breast, lung, and prostate cancer. The goals of
      treatment for such skeletal complications are to relieve pain and reduce the risk
      of fracture. Traditional therapies to treat skeletal malignancies include
      radiation, surgery, and chemotherapy. In recent years, bisphosphonates have
      become the treatment of choice because of their ability to reduce bone
      resorption, leading to decreases in hypercalcemia, new osteolytic lesions, and
      fractures, thereby ameliorating pain and improving quality of life.

PMID- 16969121
TI  - Radiosensitizing effects of the prenyltransferase inhibitor AZD3409 against RAS
      mutated cell lines.
AB  - Mutations at the H-, N- and K-ras loci are among the most frequent genetic
      alterations in human cancers. In this study, we have investigated the effect of
      AZD3409, a novel, peptidomimetic prenyltransferase inhibitor (PTI), on the
      radiosensitivity of cells with mutated ras alleles. AZD3409, developed by
      AstraZeneca, inhibits both farnesyl- and geranylgeranyl transferase in cell free
      systems. AZD3409 inhibits the growth of a variety of human cancer cell lines,
      including cells that express mutant alleles of either K- or H- ras and was well
      tolerated when administered orally to healthy volunteers in a phase I clinical
      trial. We have previously shown that PTI can radiosensitize human and rodent
      cancer cell lines that express activated RAS. Here we assessed the ability of
      AZD3409 to radiosensitize human cancer cell lines in vivo and in vitro and the
      activation state of RAS proteins in treated cells. Once daily oral administration
      of AZD3409 to nude mice bearing PSN-1 and MiaPaCa-2 human pancreatic cancer
      xenografts expressing mutant K-ras was well tolerated and resulted in a supra
      additive reduction in clonogenic cell survival after irradiation. Similarly,
      AZD3409 reduced clonogenic survival in cells that express either mutant K- or H-
      ras in vitro. We next examined the effect of AZD3409 on the processing and
      activation of K- and H-RAS. AZD3409-mediated radiosensitization, both in vivo and
      in vitro, correlates with a decrease in H-RAS processing without detectable
      effect on K-RAS processing. RAS activation assays show that the decreased H-RAS
      processing is accompanied by decreased H-RAS activation in cell lines with
      mutations in either K- or H-ras. However, no decrease in K-RAS activation was
      detected. Thus, radiosensitization of human cancer cells that express mutated K
      RAS occurred under conditions where AZD3409 inihibits the activation of
      farneyslated H-RAS, but did not inhibit K-RAS activation.

PMID- 16969122
TI  - Therapeutic targets: MTOR and related pathways.
AB  - The mammalian target of rapamycin (mTOR), a protein kinase of the
      phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, has a central role in
      controlling malignant cellular growth. As a result, mTOR is viewed as an
      important target for anticancer drug development. Inhibitors of mTOR currently
      under evaluation in cancer clinical trials are rapamycin (also known as
      sirolimus, Wyeth) and derivatives temsirolimus (CCI-779, Wyeth), everolimus,
      (RAD001, Novartis Pharma AG), and AP23573 (Ariad Pharmaceuticals). Preclinical
      studies suggest that sensitivity to mTOR inhibitors may correlate with activation
      of the PI3K pathway and/or with aberrant expression of cell cycle regulatory or
      anti-apoptotic proteins. Clinical trial results show that mTOR inhibitors are
      well tolerated and may induce prolonged stable disease and tumor regressions in
      cancer patients. Future research should evaluate optimal, schedule, patient
      selection, and combination strategies for this novel class of agents.

PMID- 16969123
TI  - Hepatic transport, metabolism and biliary excretion of irinotecan in a cancer
      patient with an external bile drain.
AB  - BACKGROUND: Irinotecan is metabolized by various enzymes, including
      carboxylesterases, cytochrome P450 3A isozymes (CYP3A) and uridine-diphosphate
      glucuronosyltransferase 1A isoforms (UGT1A). Here we report on the disposition of
      irinotecan and its metabolites in plasma, urine, bile and feces of a single
      cancer patient with an external bile drain. METHODOLOGY: Irinotecan (450 mg) was
      administered during a 90-minutes continuous infusion to a cancer patient with an
      external bile drain. Blood samples were collected up to 55 hours after infusion,
      while bile, feces and urine were collected during six consecutive days after
      administration. Samples were analyzed using high-performance liquid
      chromatography (HPLC)-assays with fluorescence detection. RESULTS: Plasma
      pharmacokinetics were characterized by a relatively slow clearance of irinotecan
      and a relatively high exposure to 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1
      piperidino] carbonyloxycamptothecin (APC). Exposures to the other metabolites was
      within the normal range. Overall, 83.4% of the administered dose was recovered in
      the excreta, with the majority excreted during the first 24 hours. CONCLUSIONS:
      Enterohepatic recirculation is of minor importance for the plasma disposition of
      irinotecan and its metabolites. The high percentage of the dose recovered in
      urine, the relatively slow clearance of irinotecan and the preferential urinary
      over biliary excretion of APC in this particular patient are likely related to
      reduced functioning of ABC-transporters. Circumstantial evidence was found that
      APC is subject to further intestinal biotransformation indicating a role in the
      etiology of irinotecan-induced diarrhea. Since intra-luminal exposure to SN-38 in
      patients with an external bile drain is limited, neutropenia will be the dose
      limiting toxicity. Based on presented data, although collected from only one
      patient, irinotecan therapy in patients with an external bile drain is feasible.
      No a priori dose adjustments are recommended, although in the absence of severe
      side-effects in previous courses, a higher dose may be considered.

PMID- 16969124
TI  - The radiosensitization effect of 2-deoxy-D-glucose on human glioma cells.

PMID- 16969125
TI  - The biochemical changes associated with phytic Acid on induced breast
      proliferative lesions in rats: preliminary findings.
AB  - BACKGROUND: Phytic acid is an anti-neoplastic agent. We hypothesize that during
      mammary tumorigenesis, the administration of phytic acid is associated with
      biochemical changes including enhancement of apoptosis and inhibition of
      oxidative stress. MATERIALS AND METHODS: An animal model formed of 25 rats was
      established. The animals were divided into three groups: (1) a control group
      which received the same phytic acid treatment in the right route and amount; (2)
      a carcinogen group which received a carcinogenic substance DMBA that can induce
      proliferative changes in the mammary gland; (3) treated group which received
      phytic acid, 60 days after the intake of DMBA. The animals were sacrificed, serum
      and tissue were evaluated for markers of tumori-genicity (serum total sialic
      acid, TSA); apoptotic changes (tissue caspase-3 activity and % DNA Fragmentation)
      and oxidative stress (tissue level of nitric oxide, NO). RESULTS: Following DMBA
      administration, benign proliferative breast changes occurred in all animals.
      However, these changes disappeared following phytic acid treatment. As compared
      to the control group, the development of these proliferative changes in DMBA
      group was associated with statistically significantly (p < 0.05) increased levels
      of TSA and NO and decreased apoptotic activity. When compared to DMBA group, the
      disappearance of the proliferative changes in phytic acid -treated group was
      associated with statistically significantly (p < 0.05) decreased levels of TSA
      and NO and increased apoptotic activity. CONCLUSIONS: Administration of phytic
      acid reversed the proliferative effects of DMBA, suggesting its protective role.

PMID- 16969126
TI  - Identification and characterization of proteins interacting with Traf4, an
      enigmatic p53 target.
AB  - Tumor necrosis factor receptor associated factor 4 (Traf4) mRNA expression is
      upregulated in various breast tumors and tumor cell lines. We previously
      identified Traf4 as a p53 target gene, and showed overexpression of Traf4
      inhibited colony formation. However, basal Traf4 expression in cell lines does
      not appear to be dependent entirely on p53. To address the putative function of
      Traf4, a yeast 2-hybrid screen and coimmunoprecipitation/mass spectrometry
      experiments were performed to identify Traf4-interacting proteins. A yeast 2
      hybrid using full length Traf4 as bait yielded several candidate interacting
      proteins including beta-catenin, GRIM19, PSMC3, p62 and dynamin. Although all of
      these proteins are novel interactors for Traf4, PSMC3 and p62 have been
      previously demonstrated to interact with the related protein, Traf6. Traf4
      appears to enhance beta-catenin related transcription as well as to provide some
      protection of beta-catenin protein levels from p53-mediated degradation although
      a direct interaction was not observed in mammalian cells. To obtain interacting
      proteins using a more physiologically relevant environment, we immunoprecipitated
      Flag-tagged Traf4 followed by mass spectrometry which identified other novel
      Traf4 interacting proteins including Eg5, PRMT5, and MYH-9.

PMID- 16969127
TI  - The limitless role of p53 in cell cycle machinery: good news or bad news?
AB  - The p53 tumor suppressor gene acts as a great protagonist in deciding how cells
      undergo either cell cycle arrest or apoptosis after experiencing various stress
      signals, including DNA damage, hypoxia, oncogene activation, and
      hyperproliferation. Research on p53 is in steady expansion, as evidenced by the
      continual flood of papers claiming novel mutations, gain or loss of p53
      functions, and gene interactions. The latest study carried out by Spurgers of
      Texas University and his Colleagues (J Biol Chem 2006; 281:25134-42) emphasizes
      the strong impact of p53 in the complicated machinery that regulates cell cycle
      progression. In this paper, microarray data and well-evaluated statistical
      procedures on PC3 and LNCaP prostate carcinoma cells, open new perspectives in
      p53 mechanisms and bring the simultaneous identification of novel p53-repressed
      cell cycle genes, hopefully providing significant improvements in the study of
      DNA damage response, multistep carcinogenesis, and treatment rationales and
      outcomes.

PMID- 16969128
TI  - Role of autophagy in cancer: management of metabolic stress.
AB  - Human breast, ovarian, and prostate tumors display allelic loss of the essential
      autophagy gene beclin1 with high frequency, and an increase in the incidence of
      tumor formation is observed in beclin1(+/-) mutant mice. These findings suggest a
      role for beclin1 and autophagy in tumor suppression; however, the mechanism by
      which this occurs has been unclear. Autophagy is a bulk degradation process
      whereby organelles and cytoplasm are engulfed and targeted to lysosomes for
      proteolysis,(1,2) There is evidence that autophagy sustains cell survival during
      nutrient deprivation through catabolism, but also that autophagy is a means of
      achieving cell death when executed to completion. If or how either of these
      diametrically opposing functions proposed for autophagy may be related to tumor
      suppression is unknown. We found that metabolic stress is a potent trigger of
      apoptotic cell death, defects in which enable long-term survival that is
      dependent on autophagy both in vitro and in tumors in vivo.(3) These findings
      raise the conundrum whereby inactivation of a survival pathway (autophagy)
      promotes tumorigenesis. Interestingly, when cells with defects in apoptosis are
      denied autophagy, this creates the inability to tolerate metabolic stress,
      reduces cellular fitness, and activates a necrotic pathway to cell death. This
      necrosis in tumors is associated with inflammation and enhancement of tumor
      growth, due to the survival of a small population of surviving, but injured,
      cells in a microenvironment that favors oncogenesis. Thus, by sustaining
      metabolism through autophagy during periods of metabolic stress, cells can limit
      energy depletion, cellular damage, and cell death by necrosis, which may explain
      how autophagy can prevent cancer, and how loss of a survival function can be
      tumorigenic.

PMID- 16969129
TI  - Functions of PI4P and sterol glucoside are necessary for the synthesis of a
      nascent membrane structure during pexophagy.
AB  - We recently showed that, in the yeast Pichia pastoris, an ergosterol glucoside
      synthesizing enzyme, Atg26, is recruited to the precursor of the pexophagic
      structure, micropexophagic membrane apparatus (MIPA), under the regulation of
      phosphatidylinositol 4'-monophosphate (PI4P)-signaling during pexophagy. Atg26
      was found to harbor a novel PI4P-binding motif, the GRAM domain. Both lipids,
      PI4P and sterol glucoside, synthesized by PpPik1 and PpAtg26, respectively, were
      necessary for pexophagy, in the step where the MIPA was formed. In this addendum,
      we review these findings, and speculate on the mechanistic and physiological
      implications of the functions of these lipids during the autophagic process.

PMID- 16969130
TI  - Probiotics, prebiotics and synbiotics: a role in chemoprevention for colorectal
      cancer?
AB  - Colorectal cancer (CRC) is the third most common form of cancer. Current
      treatments including chemotherapy, radiotherapy and surgery are all associated
      with a high risk of complications and are not always successful, highlighting the
      need to develop new treatment strategies. The ingestion of probiotics, prebiotics
      or combinations of both (synbiotics) represents a novel new therapeutic option.
      Probiotics and prebiotics act to alter the intestinal microflora by increasing
      concentrations of beneficial bacteria such as lactobacillus and bifidobacteria,
      and reducing the levels of pathogenic micro-organisms. This strategy has the
      potential to inhibit the development and progression of neoplasia via mechanisms
      including; decreased intestinal inflammation, enhanced immune function and anti
      tumorigenic activity, binding to potential food carcinogens including toxins
      found in meat products, and a reduction in bacterial enzymes which hydrolyse
      precarcinogenic compounds, such as beta-glucuronidase. There is substantial
      experimental evidence to suggest that probiotics and prebiotics may be beneficial
      in the prevention and treatment of colon cancer, however to date there have been
      few conclusive human trials. Probiotics and prebiotics have the potential to
      impact significantly on the development, progression and treatment of colorectal
      cancer and may have a valuable role in cancer prevention.

PMID- 16969131
TI  - Selective induction of necrotic cell death in cancer cells by beta-lapachone
      through activation of DNA damage response pathway.
AB  - Most efforts thus far have been devoted to develop apoptosis inducers for cancer
      treatment. However, apoptotic pathway deficiencies are a hallmark of cancer
      cells. We propose that one way to bypass defective apoptotic pathways in cancer
      cells is to induce necrotic cell death. Here we show that selective induction of
      necrotic cell death can be achieved by activation of the DNA damage response
      pathways. While beta-lapachone induces apoptosis through E2F1 checkpoint
      pathways, necrotic cell death can be selectively induced by beta-lapachone in a
      variety of cancer cells. We found that beta-lapachone, unlike DNA damaging
      chemotherapeutic agents, transiently activates PARP1, a main regulator of the DNA
      damage response pathway, both in vitro and in vivo. This occurs within minutes of
      exposure to beta-lapachone, resulting in selective necrotic cell death.
      Inhibition of PAR blocked beta-lapachone-induced necrosis. Furthermore, necrotic
      cell death induced by beta-lapachone was significantly reduced in PARP1 knockout
      cell lines. Our data suggest that selective necrotic cell death can be induced
      through activation of DNA damage response pathways, supporting the idea of
      selective necrotic cell death as a therapeutic strategy to eliminate cancer
      cells.

PMID- 16969132
TI  - Functional variant in the 3'-untranslated region of Toll-like receptor 4 is
      associated with nasopharyngeal carcinoma risk.
AB  - Signaling pathways activated by the Toll-like receptor 4 (TLR4) involve the
      induction of anti-cancer immunity. While screening for nasopharyngeal carcinoma
      (NPC) susceptibility genes, we isolated TLR4 and found that the 3'-untranslated
      region (3'-UTR) of exon 4 contained two polymorphisms that may alter its
      translation efficiency, potentially leading to NPC. To test this hypothesis, we
      conducted a hospital-based case-controlled study on NPC patients and cancer-free
      controls. We determined that the variant allele 11350C and the 11350GC genotype
      were associated with a significantly increased risk for NPC. We also determined
      significant differences between the male gender group and the remaining patient
      cases and controls, and between subjects equal to or younger than 47 years old
      and the cases and controls. Secondly, we cloned the entire 3'-UTR into a
      luciferase reporter system, and compared the luciferase activities between the
      wild-type 3'-UTR construct (WILD) and a construct containing the 11350C variant
      (MUT). Both constructs caused lower reporter gene activities, as compared to the
      positive control pGL3-promoter plasmid. Sixty hours after the transfections, the
      MUT construct reduced the reporter gene activity by 40% compared to that of the
      WILD construct (P<0.05). Functional analyses of the 11350C variant suggested that
      the TLR4 3'-UTR is a potent regulator of gene expression, as the mutated TLR4 3'
      UTR was associated with decreased mRNA stability, and may down-regulate TLR4
      expression resulting in EBV metainfective antiviral immunologic deficits and a
      high risk of NPC.

PMID- 16969133
TI  - p27Kip1 and cyclin dependent kinase 2 regulate passage through the restriction
      point.
AB  - When quiescent cells are stimulated to reenter the cell cycle, growth factors are
      required only until the restriction point in G(1) phase. After this point the
      cell no longer requires growth factors, proliferative signaling molecules, or
      even protein synthesis in order to initiate DNA synthesis, which starts several
      hours later. Consequently, understanding the molecular nature of the restriction
      point constitutes one of the major goals in studies of growth regulation. We
      recently demonstrated that p27Kip1 (p27) regulates passage through G(1) phase in
      actively proliferating cultures, and initiated these studies to determine if it
      is also involved in passage through the restriction point following stimulation
      of quiescent cells. In support of this suggestion, we found that passage through
      the restriction point requires mitogen-dependent suppression of the high p27
      levels normally present in quiescent cells. Moreover, as the culture progresses
      to mid-G(1) phase, the proportion of cells that pass the restriction point is
      increased by artificial suppression of p27 levels, while this proportion is
      reduced by elevation of p27 levels. p27 performs this critical function by
      regulating the subsequent activating phosphorylation of cyclin dependent kinase
      (CDK)2, which we also show is necessary for and closely associated with the
      initiation of DNA synthesis. We conclude that the p27 expression level at mid
      G(1) phase determines when a cell passes through the restriction point, and does
      so by regulating subsequent CDK2 activation.

PMID- 16969134
TI  - The role of Vpr in HIV-1 disease progression is independent of its G2 arrest
      induction function.
AB  - Vpr (viral protein R) is a vital HIV-1 accessory protein with multiple functions
      in the viral life cycle, including nuclear import of preintegration complex,
      induction of apoptosis and G(2) cell cycle arrest. The cell cycle perturbation
      activity of Vpr requires activation of the ATR (Ataxia-Telangiectasia and Rad3
      related) pathway and the integrity of Vpr C-terminal motif that is crucial for
      chromatin binding. Recent studies also demonstrated Vpr as one of the viral
      factors that influence HIV disease progression, as mutations in Vpr were
      overrepresented in some cohorts of long-term nonprogressors (LTNP). The LTNP
      associated mutations of Vpr are frequently observed in the C-terminal domain.
      This raises the question whether the LTNP phenotype of Vpr is the result of the
      loss its ability to induce G(2) arrest. Here we report that the LTNP-associated
      mutants of Vpr function normally in the induction of G(2) arrest. No defects in
      ATR activation and direct binding to chromatin are observed. These mutants also
      show similar levels of apoptosis induction as wild-type Vpr. These data
      differentiate the LTNP-associated mutations of Vpr with those defective in
      inducing G(2) arrest. We propose that the G(2) arrest function of Vpr is
      separated from the LTNP phenotype, and the role of Vpr in HIV disease progression
      may involve other functions of Vpr.

PMID- 16969135
TI  - Cells that trigger fever.
AB  - Bacterial lipopolysaccharide (LPS) is recognized by several receptors, including
      the toll-like receptor (TLR) 4, on various cells. Among many biological responses
      to LPS is fever, an often polyphasic rise in body temperature that is thought to
      be mediated by prostaglandin (PG) E(2). Which receptors on which cells are linked
      to fever production is unknown. It is also unknown which cells produce PGE(2)
      that triggers the earliest (first) phase of fever. Two recent studies from our
      group answer these questions. In the first one, we studied LPS-induced fever in
      mouse chimeras selectively lacking the TLR4 in hematopoietic or nonhematopoietic
      cells. We found that the first phase of fever is triggered via the TLR4 on
      hematopoietic cells. In the second study, we investigated LPS fever in rats. We
      found that the number of cells expressing cyclooxygenase (COX)-2, a PGE(2)
      synthesizing enzyme, surged at the onset of fever in the lung and liver (but not
      in the brain), and that most of these cells were macrophages. Because LPS-induced
      PGE(2) production in macrophages is TLR4-dependent, it is tempting to speculate
      that the TLR4-bearing, bone marrow-derived cells implicated in fever pathogenesis
      by the first study are the same as the COX-2-positive macrophages identified in
      the second study. Hence, pulmonary and hepatic macrophages that recognize LPS via
      the TLR4 and rapidly produce PGE(2) are likely triggers of the fever response.

PMID- 16969136
TI  - Aurora-A kinase and inhibitor-2 regulate the cyclin threshold for mitotic entry
      in Xenopus early embryonic cell cycles.
AB  - The abrupt activation of CDK1 during mitotic entry requires suppression of CDK
      activity until a threshold concentration of cyclin B is synthesized, triggering
      the activation of a large pool of CDK. The cellular mechanisms that define the
      concentration of cyclin B at which the threshold occurs are unknown. Here we
      demonstrate that this threshold is regulated by Aurora-A kinase and phosphatase
      Inhibitor-2. In Xenopus CSF extracts that actively translate cyclin B1,
      immunodepletion of either endogenous xInhibitor-2 or endogenous xAurora-A caused
      delayed mitotic entry and normal timing was restored by addition of the
      respective recombinant proteins. Aurora-A depleted extracts also could be rescued
      by the addition of full-length xInhibitor-2, but not an xInhibitor-2 truncated of
      its PP1 binding motif. This demonstrates that inhibition of PP1 was required to
      compensate for the absence of Aurora-A. To test the hypothesis that the delays in
      mitotic entry in CSF extracts were due to increases in cyclin B thresholds, we
      employed interphase extracts, which are driven into mitosis by the addition of
      recombinant cyclin B in a nonlinear (threshold) dose-response. Neutralization of
      endogenous xInhibitor-2 or xAurora with antibodies increased the cyclin B
      threshold concentration. Alternatively, the addition of exogenous Aurora-A or
      Inhibitor-2 lowered the concentration of cyclin B that triggered CDK activation.
      Because the cyclin B threshold could be raised or lowered by changing the amount
      of either Aurora-A or Inhibitor-2, the results demonstrate these regulatory
      proteins are involved in a signaling loop required to create the switching
      behavior characteristic of mitotic entry.

PMID- 16969138
TI  - Physician-directed primary care intervention to reduce risk factors for type 2
      diabetes in high-risk youth.
AB  - BACKGROUND: The incidence of type 2 diabetes in youth is increasing at an
      alarming rate. The purpose of this pilot study was to determine whether a
      nutrition and physical activity intervention in an urban primary care office is
      feasible and effective in decreasing risk factors for type 2 diabetes in high
      risk youth. METHODS: A one-group pretest/post-test design was used. Participants
      were recruited from existing patients in a primary care facility serving low
      income children. Inclusion criteria included body mass index (BMI) over the 85th
      percentile for age and a fasting glucose-insulin ratio (FGIR) less than 6. Thirty
      six African-American patients, 9 males, 27 females, average age 12.4 years
      (range, 8-18) participated in a 12-week nutrition and physical activity program.
      Measurements included fasting glucose, insulin, FGIR, lipid profile, blood
      pressure, and BMI. BMI and laboratory values were tested for significant
      differences before and after intervention using paired t-tests. A P-value of <.05
      was considered statistically significant. RESULTS: On average, patients attended
      8.3 of 24 physical activity sessions, 2 of 3 nutrition sessions and 1.5 of 3
      planned clinical sessions. Twenty-six of 36 patients completed follow-up
      laboratory tests. Mean FGIR improved significantly from baseline (3.6 +/- 1.2 to
      4.6 +/- 2.8; P = .043). CONCLUSIONS: A nutrition and physical activity
      intervention for overweight children can be conducted in an urban primary care
      setting and may decrease laboratory evidence of insulin resistance, a risk factor
      for type 2 diabetes. Making the program accessible by public transit and
      scheduling the sessions at convenient times were important factors.

PMID- 16969139
TI  - Secondary hyperparathyroidism and hypovitaminosis D in African-Americans with
      decompensated heart failure.
AB  - OBJECTIVE: We previously noted secondary hyperparathyroidism (SHPT) in African
      American patients hospitalized during February, 2005 with either untreated or
      treated congestive heart failure (CHF) due to ischemic or idiopathic
      cardiomyopathy. Herein, we hypothesized that housebound African-American patients
      hospitalized during the period of June 1 through August 31, 2005, with CHF would
      have SHPT and hypovitaminosis D. METHODS: Twenty-five African-American patients
      with an ejection fraction (EF) less than 35% due to ischemic or dilated
      (idiopathic) cardiomyopathy were monitored: 20 were hospitalized with CHF,
      stratified on historical grounds as of 4 weeks' or longer duration or of 1 to 2
      weeks' duration in 11 and 9 patients, respectively, despite medical care that
      included furosemide; serum parathyroid hormone (PTH) and 25(OH)D at the time of
      admission in these patients were compared to five asymptomatic outpatients seen
      during the summer with stable, compensated failure. RESULTS: Serum PTH was
      elevated (127 +/- 13; 82-243 pg/mL) in all patients with CHF of 4 weeks' or
      longer duration (normal, 12-65 pg/mL) and was elevated in three of nine patients
      (59 +/- 8; 18-99 pg/mL) with CHF of 1 to 2 weeks' duration. Ionized hypocalcemia
      (1.09 +/- 0.03 and 1.08 +/- 0.02 mmol/L; normal, 1.12-1.30) and hypomagnesemia
      (0.47 +/- 0.02 and 0.46 +/- 0.03 mmol/L; normal, 0.53-0.67) were respectively
      found in long- or short-duration CHF. No compensated patient had elevated PTH (42
      +/- 5; 17-53). Hypovitaminosis D (< or =30 ng/mL) was universally present in
      patients with CHF of 4 weeks' or longer duration (15.1 +/- 1.4; 7.0-23.8 ng/mL)
      and was also prevalent in the other groups (20.3 +/- 5.1, 7.0-54.1 ng/mL in CHF
      of 1 to 2 weeks' duration and 23.1 +/- 4.9; 17.2-42.7 ng/mL in compensated
      failure). CONCLUSIONS: In African-American patients with CHF, hypovitaminosis D,
      aldosteronism, and loop diuretic treatment each exaggerate Ca and Mg losses to
      stress a fragile Ca balance leading to ionized hypocalcemia and hypomagnesemia
      with SHPT.

PMID- 16969140
TI  - Prevalence and evaluation of B12 deficiency in patients with autoimmune thyroid
      disease.
AB  - BACKGROUND: Patients with autoimmune thyroid disease (AITD) have a higher
      prevalence of pernicious anemia compared with the general population. Clinical
      signs of B12 deficiency may be subtle and missed, particularly in patients with
      known autoimmune disease. We assessed the prevalence of vitamin B12 deficiency in
      patients with AITD and whether their evaluation may be simplified by measuring
      fasting gastrin levels. METHODS: Serum B12 levels was measured in 115 patients
      with AITD (7 men and 108 women), with a mean age of 47 +/- 15 years. In patients
      with low serum B12 levels (< or =133 pmol/L), fasting serum gastrin and parietal
      cell antibodies (PCA) were measured. RESULTS: Thirty-two patients (28%) with AITD
      had low B12 levels. Fasting serum gastrin was measured in 26 and was higher than
      normal in 8 patients. PCA were also measured in 27 patients with B12 deficiency
      and were positive in 8 patients. Five patients with high gastrin levels underwent
      gastroscopy with biopsy, and atrophic gastritis was diagnosed in all. The
      prevalence of pernicious anemia as assessed by high serum gastrin levels in
      patients with low B12 was 31%. CONCLUSIONS: Patients with AITD have a high
      prevalence of B12 deficiency and particularly of pernicious anemia. The
      evaluation of B12 deficiency can be simplified by measuring fasting serum gastrin
      and, if elevated, referring the patient for gastroscopy.

PMID- 16969141
TI  - A mariner with crippling arthritis and bleeding eyes.
AB  - A 41-year-old mariner developed acute arthritis affecting his legs more than his
      arms or hands during a violent storm on his return from the first of four voyages
      of discovery. He experienced repeated attacks of the arthritis over the ensuing
      14 years, which on at least two occasions were accompanied by painful eyes "much
      affected with bleeding." He died shortly before his 55 birthday "quite paralyzed
      and bedridden." Who was he, and what was the likely etiology of his disorder?

PMID- 16969142
TI  - Internal jugular vein thrombosis following mild ovarian hyperstimulation syndrome
      in women with factor V Leiden mutation.
AB  - OBJECTIVE: To study two women who presented with internal jugular vein thrombosis
      that developed shortly after in vitro fertilization (IVF) therapy complicated by
      mild ovarian hyperstimulation syndrome (OHSS). METHODS: Evaluation of the past
      medical history, treatment, laboratory studies, and clinical outcome of both
      patients. RESULTS: The two patients were found to be carriers for factor V Leiden
      mutation (FVLM). One was homozygote and the other heterozygote for that mutation.
      The genetic predisposition probably contributed to the development of an early
      thrombosis in these patients despite the mildness of their OHSS. In the
      homozygote patient, the dose of low molecular weight heparin was reduced due to
      vaginal bleeding. Afterwards, fetal loss due to an extensive placental infarction
      occurred. Infarction was confined to maternal side while the fetal side vessels
      were spared. CONCLUSION: We suggest that women of European descent, especially
      those with personal or familial history of thromboembolic events, should be
      screened for FVLM before IVF treatment. In those found to be carriers of FVLM,
      preventive anticoagulation should be considered.

PMID- 16969143
TI  - An unusual cause of muscle weakness: a case report.
AB  - Thyrotoxic hypokalemic periodic paralysis (THPP) has been reported earlier in the
      Asian population. However, it is now becoming increasingly common in the Western
      countries as well. Thus, its in-depth knowledge is a must for every physician so
      that this diagnosis is not overlooked in any case presenting with extremity
      weakness and paralysis, especially considering its reversible nature. We present
      an interesting case of THPP in a Vietnamese patient presenting with bilateral
      lower extremity weakness and extremely low serum potassium levels. We also
      present a comprehensive discussion and review of literature related to THPP,
      which would be helpful for the internists to diagnose and appropriately manage
      this disease.

PMID- 16969144
TI  - A case of classical polyarteritis nodosa complicated by ulcerative colitis.
AB  - Classical polyarteritis nodosa (PAN) is a term that includes patients with
      necrotizing inflammation of medium-sized arteries and excludes those with
      microscopic vessel involvement. Although gastrointestinal manifestations are not
      unusual in patients with classical PAN, the association with ulcerative colitis
      has been reported only rarely. We describe a patient with classical PAN
      complicated by bilateral renal artery aneurysms with subsequent rapture and
      perirenal hemorrhages. He was successfully treated, and the bilateral renal
      aneurysms resolved with steroid therapy. Two years later, the patient presented
      with hematochezia. Colonoscopy revealed inflamed rectal mucosa with bleeding
      ulcers. Histologic findings of biopsy specimens showed severe mucosal
      inflammation and crypt abscess. The patient was diagnosed with ulcerative
      colitis, and the symptoms attenuated after meselazine therapy.

PMID- 16969145
TI  - Hyperthyroidism: a rare cause of reversible pulmonary hypertension.
AB  - We describe a case of pulmonary hypertension and high-output heart failure in a
      61-year-old woman suffering from relapsing Graves disease. The patient
      experienced prompt hemodynamic and symptomatic recovery after normal thyroid
      function was restored. Possible mechanisms for the development of pulmonary
      arterial hypertension due to hyperthyroidism include damage to pulmonary vascular
      endothelium due to high cardiac output or an autoimmune process or increased
      metabolism of intrinsic pulmonary vasodilators. Another possible mechanism is
      vascular vasoconstriction due to decreased cholinergic output.

PMID- 16969146
TI  - Oncogenic osteomalacia in a case with a maxillary sinus mesenchymal tumor.
AB  - We herein describe the rare case of a 41-year-old woman with oncogenic
      osteomalacia due to a tumor in the maxillary sinus who presented with chronic
      general pain that had been gradually deteriorating. The patient's laboratory
      findings revealed hypophosphatemia due to renal phosphate wasting, an
      inappropriately low serum 1 alpha,25-dihydroxyvitamin D3 level for
      hypophosphatemia and an unusually high serum level of fibroblast growth factor 23
      (FGF23). The causative tumor was surgically removed, resulting in a rapid
      resolution of the patient's biochemical abnormalities. An improvement of the
      abnormal multiple deposits on (99)Technetium-methylene diphosphonate bone
      scintigraphy and an increase in the bone metabolism markers suggested the
      development of bone remodeling within 49 days after the operation. The pathologic
      diagnosis of the tumor was a "phosphaturic mesenchymal tumor, mixed with a
      connective tissue variant." The expression of FGF23 was demonstrated in the tumor
      by the immunohistochemical techniques and a Western analysis.

PMID- 16969147
TI  - Pleural fluid and peripheral eosinophilia from hemothorax: hypothesis of the
      pathogenesis of EPE in hemothorax and pneumothorax.
AB  - Blood and air in the pleural space are the most common conditions associated with
      an eosinophilic pleural effusion. The recruitment of eosinophils is dependent
      upon stimulation by cytokines, specifically interleukin (IL)-3, IL-5, granulocyte
      monocyte cell stimulating factor (GM-CSF), and RANTES (regulated upon activation,
      normal t-cell expressed and secreted), that cause eosinophil proliferation in the
      bone marrow, movement into the circulation, and adhesion and migration across
      endothelial barriers into tissues. There are several possible mechanisms that can
      explain eosinophilic pleural effusions. We report a case of an eosinophilic
      pleural effusion after spontaneous hemothorax that illustrates the course of
      pleural fluid and blood eosinophilia in following hemothorax and describe the
      different pathophysiology of eosinophil trafficking in the pleural space and
      serum following hemothorax and pneumothorax.

PMID- 16969148
TI  - Colonoscopy-associated pneumothorax: a case of tension pneumothorax and review of
      the literature.
AB  - A 64-year-old woman presented with severe abdominal pain and was found to have a
      large fecolith in the sigmoid colon with resulting bowel obstruction. During a
      therapeutic colonoscopy, she developed severe shortness of breath and hypoxia,
      and was found to have a tension pneumothorax. We review the potential mechanisms
      by which pneumothorax may occur following colonoscopy. In addition, the eight
      previously published cases are reviewed. Pneumothorax, with or without
      pneumomediastinum, can occur through a variety of mechanisms following
      colonoscopy. Although rarely reported, this may represent an underappreciated
      complication and should be fully investigated in the appropriate setting.
      Colonoscopy, an exceedingly common procedure, will continue to increase with the
      aging population. As a result, tension pneumothorax can have a profound effect on
      the patient outcome and therefore physicians, both gastroenterologists and
      pulmonologists, should be aware of all the potential problems with this
      procedure.

PMID- 16969149
TI  - Removal of methotrexate by peritoneal dialysis and hemodialysis in a single
      patient with end-stage renal disease.
AB  - BACKGROUND: Although methotrexate is highly bound to albumin, it is thought to be
      removed by hemodialysis and not by peritoneal dialysis. We are not aware of any
      direct comparison in the same patient. CASE REPORT/METHODS: A 60-year-old patient
      on continuous ambulatory peritoneal dialysis was admitted to the East Alabama
      Medical Center for stomatitis and pancytopenia after being given 10 mg of
      methotrexate for his rheumatoid arthritis. Measurements of total methotrexate
      levels were made before, during, and after sequential peritoneal and hemodialysis
      treatments. RESULTS: We found that the clearance of methotrexate measured in the
      dialysate was equal in the first hour of dialysis for both types of dialysis,
      although serum levels were markedly lower in hemodialysis compared to peritoneal
      dialysis. CONCLUSION: Methotrexate was cleared by peritoneal dialysis in the
      first hour of an exchange and was not associated with a rebound in serum levels.
      Hemodialysis was associated with lower serum levels; however, there was also a
      significant rebound 2 hours after the procedure ended. Since neither procedure
      was able to preclude the death of the patient, other more effective means of
      methotrexate elimination should be employed.

PMID- 16969151
TI  - The inflamed peripheral nervous system: update on immune therapies.

PMID- 16969152
TI  - Immune circuitry in the peripheral nervous system.
AB  - PURPOSE OF REVIEW: The aim of this review is to describe the local immune
      circuitry in the peripheral nervous system and its dialogue with systemic
      immunity under pathological conditions. Specifically, interactions of the immune
      system with cellular and extracellular components within peripheral nerve and
      immune functions of tissue-resident endoneurial macrophages and Schwann cells
      will be discussed. RECENT FINDINGS: New insights into the elements involved in
      the pathogenesis of immune-mediated disorders of the peripheral nervous system
      provide a better understanding of the complex interplay of these cellular and
      molecular components in the immunology of the peripheral nervous system. SUMMARY:
      The application of innovative and cutting-edge technologies to the study of
      immunoinflammatory disorders of the peripheral nervous system provides a better
      understanding of underlying principles of the organization of the immune network
      present in the peripheral nerve and its dialogue with the systemic immune system.
      This may foster the development of specific and highly effective therapies for
      immune-mediated disorders of the peripheral nerve.

PMID- 16969153
TI  - Recent advances in HIV neuropathy.
AB  - PURPOSE OF REVIEW: To describe recent advances in HIV neuropathy. RECENT
      FINDINGS: Epidemiologic studies since highly active antiretroviral therapy was
      introduced have shown that the incidence of HIV-associated distal sensory
      polyneuropathy is reduced. Studies have also shown the relationship between
      distal sensory polyneuropathy and the use of neurotoxic antiretroviral drugs.
      Skin punch biopsy for assessment of epidermal nerve fiber density is valuable
      both for diagnosis of distal sensory polyneuropathy and as a predictor of the
      condition occurring in the future. An in-vitro model of antiretroviral toxic
      neuropathy showed that dideoxynucleoside analogues that cause neuropathy exert
      direct mitochondrial toxicity that is not mediated indirectly through the
      inhibition of DNA polymerase-gamma. HIV envelope protein gp120 exerts axonal
      toxicity directly or indirectly via perineuronal Schwann cells. A feline model of
      HIV, infection of neonatal cats with the feline immunodeficiency virus, showed
      development of peripheral neuropathy characterized by loss of epidermal
      innervation. SUMMARY: While epidemiological studies of HIV-associated peripheral
      neuropathy continue to provide useful information, pathogenic studies are moving
      forward. Animal models of the disease will allow researchers to 'manipulate' the
      system. It is hoped that these types of studies will translate to an improved
      understanding of the pathogenesis of HIV-associated neuropathies leading to
      better treatments.

PMID- 16969154
TI  - Bacterial infections in Guillain-Barre and Fisher syndromes.
AB  - PURPOSE OF REVIEW: Progress has been made in our understanding of Guillain-Barre
      syndrome, especially in identifying the Campylobacter jejuni genes responsible
      for the development of clinical features. RECENT FINDINGS: C. jejuni is grouped
      into several classes based on the organization of lipo-oligosaccharide
      biosynthesis genes. A specific class carrying a sialyltransferase gene (cst-II)
      is associated with the development of Guillain-Barre syndrome, which is essential
      for the biosynthesis of ganglioside-like lipo-oligosaccharides. The class of C.
      jejuni expressed both GM1-like and GD1a-like lipo-oligosaccharides, which could
      induce the production of autoantibodies to GM1, to GD1a or to the GM1/GD1a
      complex, possibly increasing the risk of development. C. jejuni sialyltransferase
      (Cst-II) consists of 291 amino acids, and the 51st amino acid determines its
      enzymatic activity. Strains with cst-II (Thr51) expressed GM1-like or GD1a-like
      lipo-oligosaccharide whereas strains with cst-II (Asn51) expressed GT1a-like or
      GD1c-like lipo-oligosaccharide. Patients infected with the cst-II (Thr51) strains
      had anti-GM1 or anti-GD1a IgG antibodies, and showed limb weakness. Patients
      infected with the cst-II (Asn51) strains had anti-GQ1b IgG antibodies, and showed
      ophthalmoplegia and ataxia. SUMMARY: The cst-II gene is responsible for the
      development of Guillain-Barre and Fisher syndromes, and the polymorphism
      (Thr/Asn51) determines which syndrome develops after C. jejuni enteritis.

PMID- 16969155
TI  - Anti-myelin-associated glycoprotein neuropathy.
AB  - PURPOSE OF REVIEW: The anti-myelin-associated glycoprotein (MAG) neuropathy is an
      antibody-mediated demyelinating neuropathy. The clinical picture is characterized
      by a distal and symmetric, mostly sensory neuropathy. Monoclonal immunoglobulin M
      anti-MAG antibodies are uniquely found in this condition and are believed to be
      pathogenic. This review focuses on recent progress in understanding the
      mechanisms of this neuropathy and discusses new therapeutic advances. RECENT
      FINDINGS: Different electrophysiological parameters have been demonstrated to
      distinguish the anti-MAG-associated polyneuropathy from chronic inflammatory
      demyelinating polyneuropathy. The electrophysiological findings generally
      indicate a predominantly demyelinating neuropathy with a distal accentuation of
      conduction slowing. Analyses of pathology in nerve tissue from anti-MAG patients
      using classical nerve biopsy or skin biopsy tissue demonstrated immunoglobulin M
      deposits at the site of MAG localization, demyelination and axonal degeneration.
      MAG is a Schwann cell-based glycoprotein and has been implicated as a mediator of
      an outside-in signaling cascade influencing the cytoskeletal integrity of axons.
      SUMMARY: Therapy in patients with anti-MAG neuropathy is directed at reducing the
      antibody concentration, blocking the effector mechanisms and depleting the
      monoclonal B cells. The recent availability of rituximab, a monoclonal antibody
      suppressing B-cell clones, which is not myelosuppressive and does not cause
      secondary malignancies, allows for early targeted intervention.

PMID- 16969156
TI  - Animal models of inherited neuropathies.
AB  - PURPOSE OF REVIEW: Mutations in a number of genes have been associated with
      inherited neuropathies (Charcot-Marie-Tooth or CMT disease). This review
      highlights how animal models of demyelinating CMT have improved our understanding
      of disease mechanisms. Transgenic CMT models also allow therapies to be developed
      in a preclinical setting. RECENT FINDINGS: Rodent models for the most common
      subtypes of human CMT disease are now available, and two mouse mutants modeling
      the rare CMT4B subform have lately extended this repertoire. In a peripheral
      myelin protein 22 kDa (Pmp22) transgenic rat model of CMT1A, administration of a
      progesterone receptor antagonist reduced Pmp22 overexpression, axon loss and
      clinical impairments. Dietary ascorbic acid prevented dysmyelination and
      premature death in a Pmp22 transgenic mouse line. Neurotrophin-3 promoted small
      fiber remyelination in CMT1A xenografts and sensory functions in CMT1A patients.
      Gene expression profiling in rodent models of CMT may identify further
      therapeutical targets. While original classifications distinguish the
      demyelinating and axonal forms of CMT, recent findings emphasize that axon loss
      is a common feature, possibly caused by Schwann cell defects rather than
      demyelination per se. This supports our model that myelination and long-term
      axonal support are distinct functions of all myelinating glial cells. SUMMARY:
      Animal models have opened up new perspectives on the pathomechanisms and possible
      treatment strategies of inherited neuropathies.

PMID- 16969157
TI  - Recent advances in hereditary sensory and autonomic neuropathies.
AB  - PURPOSE OF REVIEW: This review summarizes the genetic advances of hereditary
      sensory neuropathies and hereditary sensory and autonomic neuropathies, and
      provides information on phenotype-genotype correlation and on possible underlying
      pathomechanisms. RECENT FINDINGS: Hereditary sensory neuropathies, also known as
      hereditary sensory and autonomic neuropathies, are a clinically and genetically
      heterogeneous group of disorders. These disorders are characterized by prominent
      sensory loss with acro-mutilating complications and a variable degree of motor
      and autonomic disturbances. Based on age at onset, clinical features and mode of
      inheritance, these disorders have originally been subdivided into five types. The
      identification of eight loci and six disease-causing genes for this group of
      disorders, however, has shown that this present classification has to be refined.
      SUMMARY: This review will discuss each of the different loci and genes of these
      disorders, showing glimpses into a possible underlying pathomechanism leading to
      the degeneration of sensory and autonomic neurons.

PMID- 16969158
TI  - Alcoholic neuropathy.
AB  - PURPOSE OF REVIEW: The concept of alcoholic neuropathy has been obscured because
      of an often undetected or overestimated influence of thiamine deficiency. We
      describe clinicopathologic features of alcoholic neuropathy, taking the effect of
      thiamine status into consideration, and recent progress associated with the
      pathogenesis. RECENT FINDINGS: Clinical features of alcoholic neuropathy without
      thiamine deficiency are characterized by slowly progressive, sensory-dominant
      symptoms. Superficial sensation is predominantly impaired and painful symptoms
      are the major complaint. Pathologic features are characterized by small-fiber
      predominant axonal loss. In contrast, the clinicopathologic features of alcoholic
      neuropathy with concomitant thiamine deficiency are variable, constituting a
      spectrum ranging from a picture of a pure form of alcoholic neuropathy to a
      presentation of nonalcoholic thiamine-deficiency neuropathy. One possible
      mediator of the direct neurotoxic effects among the metabolites of ethanol is
      acetaldehyde. Axonal transport and cytoskeletal properties are impaired by
      ethanol exposure. Protein kinase A and protein kinase C may also play a role in
      the pathogenesis, especially in association with painful symptoms. SUMMARY:
      Nutritional deficiency as well as the direct neurotoxic effects of ethanol or its
      metabolites can cause alcoholic neuropathy. Although clinicopathologic features
      of the pure form of alcoholic neuropathy are uniform, they show extensive
      variation when thiamine deficiency is present.

PMID- 16969159
TI  - Bibliography. Current world literature. Neuromuscular diseases: nerve.

PMID- 16969161
TI  - Recent advances in the prevention of congenital heart disease.

PMID- 16969162
TI  - Outcome of fetal cardiac defects.
AB  - PURPOSE OF REVIEW: The present review summarizes the prenatal and postnatal
      outcome of cardiac anomalies and sustained arrhythmias diagnosed during fetal
      life. RECENT FINDINGS: The outcome of sustained fetal arrhythmias has improved
      with greater experience using Sotalol for atrial flutter, and digoxin and
      amiodarone for 1: 1 reciprocating tachycardia. The outcome of fetal conduction
      system disease secondary to maternal Sjogren's antibodies has noticeably improved
      with transplacental dexamethasone. The postnatal prognosis for atrioventricular
      block associated with left atrial isomerism, however, remains very bleak.
      Assessing the effect of prenatal diagnosis on the outcome of structural defects
      remains difficult because of the high number of extracardiac anomalies and
      chromosome defects in this group. Preoperative survival is improved, but
      postoperative mortality has not improved. One clear advantage of prenatal
      diagnosis is the selection of fetuses that may benefit from in-utero intervention
      to limit the progression of their disease or lessen its severity at birth.
      SUMMARY: For the most part, postoperative mortality of structural cardiac defects
      is not significantly improved by prenatal diagnosis. In-utero management of
      tachyarrhythmias and conduction system disease has improved postnatal outcome,
      except for the fetus with atrioventricular block and left atrial isomerism.

PMID- 16969163
TI  - Advances in congenital long QT syndrome.
AB  - PURPOSE OF REVIEW: Dramatic advances have been made in understanding of both the
      genetics and the phenotypic expression of congenital long QT syndrome. This paper
      reviews recent clinically relevant literature. RECENT FINDINGS: Long QT syndrome
      is one of the leading causes of sudden cardiac death. This syndrome, once
      diagnosed by a clinical profile, has been more clearly defined by specific gene
      defects causing ion channel abnormalities in the beating heart. Genetic testing
      for long QT syndrome, once available only through research laboratories, is now
      commercially available. Diagnosis, risk assessment, and management are
      increasingly being guided by gene-specific diagnoses. In a family with suspected
      disease, the genetic test will determine the defect in as many as 75% of
      subjects. Once the diagnosis is made, the mainstay of therapy continues to be
      beta-blockers. Implantable cardioverter-defibrillators are indicated in patients
      at high risk for malignant arrhythmias. SUMMARY: Long QT syndrome is one of the
      first cardiovascular diseases to see the dramatic changes that bench research can
      bring to the clinical arena. Future research is needed to determine the gene
      defect in the remaining 25% of patients with suspected long QT syndrome and in
      risk stratification.

PMID- 16969164
TI  - Advances in cardiac intensive care.
AB  - PURPOSE OF REVIEW: As surgical survival in children with congenital heart
      disease, particularly those with univentricular hearts, has improved in recent
      years, focus has shifted to reducing the morbidity of congenital cardiac
      malformations and their treatment. This review will focus on emerging therapies
      aimed at reducing these morbidities in the intensive care unit. RECENT FINDINGS:
      A protracted stay in the intensive care unit after cardiac surgery is a risk
      factor for developing various morbidities. Therapies or interventions that may
      hasten postoperative recovery and minimize the length of stay are thus important
      to evaluate. Fluid overload, renal dysfunction, low cardiac output and
      neurological dysfunction remain major contributors to morbidity after cardiac
      surgery. In addition, the treatment of these adverse states can potentially
      compound the injury. SUMMARY: The reduction in morbidity after cardiac surgery
      remains challenging. Recent insights have allowed us to recognize the impact of
      factors beyond the intraoperative period as significant contributors to
      morbidity. As our field continues to evolve, future studies should focus on
      emerging technologies and therapies that facilitate the prevention of
      physiological states that compound congenital morbidities.

PMID- 16969165
TI  - Advances in pediatric heart transplantation.
AB  - PURPOSE OF REVIEW: Heart transplantation has become a reasonable treatment option
      for pediatric patients with end-stage heart failure or complex congenital cardiac
      defects not amenable to conventional surgical intervention. This review will
      summarize the current state of pediatric cardiac transplantation and review
      recent advances leading to new therapies. RECENT FINDINGS: Improvements in early
      mortality after cardiac transplantation have occurred consistently over time
      since the 1980s, short-term survival rates are high, and most patients enjoy an
      excellent quality of life with minimal restrictions. The reduction of late
      mortality is still a major challenge, however, largely as a result of transplant
      related coronary artery disease causing chronic graft failure and arrhythmogenic
      sudden death. Additional causes of morbidity and mortality occurring late after
      transplantation include renal dysfunction related to chronic immunosuppressive
      therapy with calcineurin inhibitors (tacrolimus or cyclosporine) and
      posttransplant lymphoproliferative disorders related to chronic
      immunosuppression. Newer agents (sirolimus, everolimus) have shown promise in
      immunosuppressive regimens that may alter the development or progression of long
      term complications. SUMMARY: New immunosuppressive agents allow alterations in
      drug regimens to minimize renal complications, and may influence the incidence
      and progression of transplant vasculopathy. Recent studies on posttransplant
      lymphoproliferative disorders should result in earlier diagnosis and therapy.

PMID- 16969167
TI  - A family systems perspective on pediatric illness.

PMID- 16969166
TI  - Stem cells for repair of the heart.
AB  - PURPOSE OF REVIEW: Stem cell therapy for treatment of cardiac disease has shown
      therapeutic potential. RECENT FINDINGS: A number of stem and progenitor
      populations have been identified for potential use in cardiac repair. Each
      possesses a unique potency that justifies consideration for use. Autologous,
      unfractionated bone marrow cells or skeletal myoblasts were used in early
      clinical trails to evaluate reparative effects on recent or record infarcts. In
      each case, evidence of limited improvement in cardiac function was obtained.
      Myoblast grafts were unexpectedly correlated with arrhythmias, thereby
      identifying a safety issue. The small number of patients and the lack of
      randomized control groups preclude conclusions regarding efficacy. Randomized
      controlled, intermediate-sized, double-blind clinical trials must be undertaken
      to this end. SUMMARY: Cellular therapy may be useful in the treatment of cardiac
      disease in adults. Appropriate adaptations to meet unique requirements for
      treatment of pediatric cardiovascular disease may be required. Bone marrow and
      skeletal myoblasts do not promote true tissue regeneration in spite of observed
      functional improvement. Trials using cells possessing true potential for
      (trans)differentiation may elucidate the potential and value of this therapy as a
      reparative modality. Development of optimal strategies for targeted delivery
      consistent with pathobiology is of exception clinical relevance.

PMID- 16969168
TI  - Facilitating family resilience with childhood illness and disability.
AB  - PURPOSE OF REVIEW: The present review describes the clinical utility of a
      research-informed Family Systems-Illness model and a family resilience framework
      in helping families meet the challenges of child and adolescent illness,
      disability, and loss. Together they provide a psychosocial map to guide families
      through the illness experience over time and to facilitate effective coping and
      adaptation, thereby enhancing the quality of life for children and their
      families. Key processes and intervention guidelines of this strengths-oriented,
      collaborative approach are outlined, with attention to multigenerational, life
      cycle, and socio-cultural influences. RECENT FINDINGS: A growing body of research
      on resilience finds that family resources are significant influences in positive
      adaptation to adversity, such as a major health problem. Research also
      demonstrates the impact of serious illness on families across the life cycle and
      the relationship of family dynamics to illness behavior, adherence, and disease
      course. SUMMARY: The Family Resilience and Family Systems-Illness models offer a
      framework for collaborative practice to foster optimal coping and adaptation to
      chronic child and adolescent illness or disability.

PMID- 16969169
TI  - Family processes in pediatric asthma.
AB  - PURPOSE OF REVIEW: Family processes are best conceptualized within an integrated,
      dynamic biopsychosocial model of pediatric asthma. We reviewed the literature on
      specific family processes proposed to influence asthma outcomes, the mechanisms
      of influence, and family-focused interventions to improve asthma control. RECENT
      FINDINGS: Family characteristics associated with asthma outcomes include
      caregiver psychological functioning, parenting, and whole-family processes. These
      characteristics influence asthma outcomes via asthma management behaviors and/or
      disease-related psychophysiologic pathways. Family-focused interventions designed
      to promote asthma control include psychoeducation and family therapy, although
      alternative models have also been proposed. SUMMARY: Despite the increasing
      evidence that family processes contribute to asthma outcomes, few theory-based
      family interventions have been developed for children with asthma. Systemic
      consultation models and biobehavioral family interventions, in conjunction with
      pediatric care, appear to hold the most promise for helping families of children
      with poorly controlled asthma.

PMID- 16969170
TI  - Family context and HIV risk among youth in psychiatric care: what pediatricians
      can do.
AB  - PURPOSE OF REVIEW: The HIV/AIDS epidemic is one of the most widespread public
      health problems today. Teens with mental health concerns are particularly
      vulnerable to infection because they engage in higher rates of risky behaviors
      than their peers. Families are vital influences in protecting teens from HIV
      exposure, but parents often feel unprepared to discuss sexual behavior with
      teens. This review provides an overview of the role of teens' mental illness in
      HIV risk and suggests guidelines for pediatricians to facilitate parents' ability
      to keep teens safe from risky behaviors. RECENT FINDINGS: Young people account
      for more than 50% of new infections each year, and mental health problems are
      related to increased risk taking via inconsistent condom use, multiple partners,
      and decreased assertiveness. Parents can protect youth from engaging in HIV risk
      behaviors through supervision, providing support, and communicating effectively
      about sexual topics. SUMMARY: Pediatricians can support parents in keeping youth
      safe from HIV infection by openly discussing ways to reduce teens' risk of
      exposure. Talking to families about risks, empowering parents to address issues
      with teens, and providing referrals for parents to build a network of support can
      reduce mental health problems and HIV risk among teens.

PMID- 16969171
TI  - Medical adherence and childhood chronic illness: family daily management skills
      and emotional climate as emerging contributors.
AB  - PURPOSE OF REVIEW: To describe recent research that examines family factors that
      promote or derail adherence to medical regimens for children with chronic health
      conditions, primarily asthma, diabetes, and cystic fibrosis. From the past 2
      years, eight correlational studies were identified which specifically examined
      the links between family management strategies, family climate and medical
      adherence. RECENT FINDINGS: Findings from the studies suggest that team-based
      management strategies and cohesive family climate promote adherence to medical
      treatments over time. Family interactions that are characterized by conflict and
      disengagement tend to disrupt adherence and inevitably cause a decline in child
      health. Moreover, these findings seem to be moderated by child age in that poorer
      adherence often occurs when a child reaches adolescence and is searching for
      greater autonomy. SUMMARY: Future research should consider the challenges in
      measuring medical adherence in the family context as well as incorporating more
      naturalistic studies of family interactions. Randomized controlled trials using
      family-based interventions may consider focusing on medical adherence as an
      important mediator between family process and child health outcomes.

PMID- 16969172
TI  - Pediatric medical traumatic stress in pediatric oncology: family systems
      interventions.
AB  - PURPOSE OF REVIEW: Traumatic stress offers a helpful framework by which the
      ongoing reactions of children with cancer and their families can be understood.
      Family systems interventions in pediatric oncology are reviewed, with a focus on
      reducing pediatric medical traumatic stress (PMTS) across members of the family.
      RECENT FINDINGS: A recently developed model of PMTS is presented and applied to
      the pediatric cancer population. Two family interventions to decrease traumatic
      stress systems are reviewed. Reductions in traumatic stress symptoms were
      observed at postintervention follow-ups for family members in both studies.
      SUMMARY: The pediatric medical traumatic stress model provides a useful heuristic
      for understanding the psychological consequences of pediatric cancer on the child
      and their family over the course of treatment and beyond. Two family systems
      interventions show promise in improving outcomes for childhood cancer survivors
      and their parents. Although interventions are promising, future development of
      these interventions to modify them for dissemination is needed.

PMID- 16969173
TI  - Foreign bodies in the gastrointestinal tract.

PMID- 16969174
TI  - The effect of childhood malnutrition on externalizing behavior.
AB  - PURPOSE OF REVIEW: Childhood externalizing behavior (aggression, hyperactivity,
      and conduct disorder) has been increasingly viewed as a public health problem
      because of its etiology and outcome. The association between malnutrition and
      externalizing behavior has begun to receive attention. This review summarizes
      recent empirical findings on malnutrition as a risk factor for the development of
      externalizing behavior, with an emphasis on micronutrient deficiency, and
      explores brain dysfunction as a possible mechanism. RECENT FINDINGS:
      Externalizing behavior is associated with both macromalnutrition (e.g. protein)
      and micromalnutrition (e.g. iron and zinc). Both prenatal and postnatal
      malnutrition is implicated. The long-term effects of malnutrition on behavior
      could be reversible. The effects of docosahexaenoic acid/omega-3 long-chain
      essential fatty acid on externalizing behavior are more mixed. From animal and
      human findings, it is hypothesized that malnutrition impairs neurocognitive
      functioning by reducing neurons, alternating neurotransmitter functioning, and
      increasing neurotoxicity, and that such neurocognitive impairments predispose to
      externalizing behavior. SUMMARY: Different lines of evidence support the view
      that poor nutrition contributes to the development of child behavior problems.
      More randomized, controlled trials that manipulate nutritional intake and
      evaluate behavior in children are needed to evaluate the etiological role of
      nutrition in externalizing behavior in order to inform intervention and
      prevention efforts.

PMID- 16969176
TI  - Bibliography. Current world literature. Cardiovascular medicine.

PMID- 16969175
TI  - Management of esophageal coins.
AB  - PURPOSE OF REVIEW: Coins are the most commonly ingested foreign body encountered
      in the pediatric population. Coins that are in the esophagus and are causing
      symptoms (cough, stridor, respiratory distress, drooling or pain) are managed
      with immediate removal via various methods. Asymptomatic coins have been a
      perplexing problem to the clinician for decades, with some advocating for
      immediate removal while others are proponents of "watchful waiting". RECENT
      FINDINGS: This article will provide a review of the current literature on
      management options for symptomatic and asymptomatic esophageal coins. The article
      will discuss clinical decision-making strategies for the diagnosis of the
      unwitnessed ingestion, as well as diagnostic studies, such as plain radiographs,
      as well as novel modalities, such as metal detectors. Discussion of the anatomic
      issues related to esophageal foreign bodies will be addressed. Treatment options
      for asymptomatic patients will be reviewed utilizing data from retrospective
      studies as well as a prospective randomized trial. SUMMARY: In the symptomatic
      patient with an esophageal coin, immediate removal via endoscopy is recommended.
      For the asymptomatic patient with an esophageal coin, current data support
      expectant management for a period of 12-24 h with the hope of spontaneous passage
      and avoidance of general anesthesia and surgical procedure.

PMID- 16969227
TI  - Abstracts of the 4th European Congress on Emergency Medicine, Herakilon, Crete, 4
      8 October 2006.

PMID- 16969228
TI  - A cadaveric study of complications associated with the subxiphoid and
      transthoracic approaches to emergency pericardiocentesis.
AB  - OBJECTIVES: The aim of this cadaveric study was to compare three commonly used
      approaches for emergency pericardiocentesis and to determine the safest approach.
      METHODS: Thirteen cadavers were injected at three sites with three different
      coloured dyes, one for each of the three different recommended approaches. The
      approaches used were (1) ATIP: anterior transthoracic in the fifth left
      intercostal space (Advanced Cardiac Life Support protocol), (2) SXP1: immediately
      subxiphoid and (3) SXP2: subxiphoid approach 1.5 cm inferior to SXP1 (Advanced
      Trauma Life Support protocol). The needles were left in the chest cavity to
      confirm their course on the way into the pericardial sac. Once the chest plate
      was removed, the location of the needle and the presence of dye enabled the
      identification of structures damaged and cavities entered by the needle. The
      associated complications from the three approaches were then recorded and
      compared. RESULTS: The anterior transthoracic intercostal pericardiocentesis
      approach to pericardiocentesis (2/39) and an immediately subxiphoid approach SXP1
      (1/39) produced fewer potential complications than SXP2 (4/39). CONCLUSIONS: The
      SXP1 approach appeared to be the safest, followed by anterior transthoracic
      intercostal pericardiocentesis. The SXP2 approach caused the highest amount of
      complications, resulting from the needle entering the abdominal cavity. The
      presence of intra-abdominal pathology and the possibility of post-mortem changes
      in the position of the diaphragm, however, might have been a causative factor in
      this finding.

PMID- 16969229
TI  - Health network to improve elderly patients' flow in emergency department.
AB  - BACKGROUND: The French population has been growing older these past decades. The
      French Regional Health Organization System authorizes the creation of health
      networks in order to improve healthcare. We have developed since 2002 in our
      Tertiary Hospital Cochin, a health network inside Paris and its suburbs for the
      elderly to improve their flow from the emergency department. Our study, based on
      this organization, analyses the outcome of such a system. METHODS: From January
      2002 to December 2002, we conducted a monocentric retrospective study from the
      emergency department including all polypathological elderly patients (older than
      75 years) admitted for a medical purpose. We classified them according to triage
      level at arrival, their duration of stay in the emergency department and in the
      tertiary hospital/geriatric network and their in-hospital mortality. RESULTS:
      Elderly patients represented 12% of our recruitment of an overall number of 42
      700 patients in 2002. Six hundred and ninety-nine (24.2%) patients needed
      admission in a geriatric field; 42.8% were hospitalized in our tertiary hospital
      and 57.2% in the geriatric network. The mean age was 86.5+/-6 years in the two
      groups. The triage scale shows that most elderly people needed rapid care in the
      emergency department. Our mean duration of stay in the emergency department was
      11 h 30 min. No significant difference was observed in the two groups for the in
      hospital duration of stay. Mortality rate was 10.2% with a significant difference
      in the two groups. CONCLUSION: We observed a decreasing number of elderly
      persons' admission in our tertiary hospital, allowing a specific activity in the
      referred medical units. Our contract with the geriatric hospital in the network
      favoured elderly patients' flow from the emergency department. The geriatric
      network hospitals could refer back any patient to the emergency department for
      emergent events.

PMID- 16969230
TI  - Low molecular weight heparin self-injection training: assessment of feasibility,
      tolerance and economic analysis in emergency departments.
AB  - BACKGROUND: The purpose of this study was to assess low molecular weight heparin
      auto-injection skills of self-supporting patients, taught by a nurse through a
      rapid demonstration in an emergency department. METHODS: The study was a
      prospective, multicentre study, carried out in emergency departments. It included
      all ambulatory attending patients over 18 years of age, who were given a lower
      limb cast in an emergency ward and provided with limited orthopaedic treatment.
      Eligible patients who accepted self-injection training were given a quick
      demonstration by the nurse in the emergency ward. A questionnaire about the
      perception of the patient was completed at the beginning of the treatment and at
      the end of the treatment. A surveillance chart for recording injections and side
      effects was also given to the patient, and platelet counts were performed twice
      weekly. FINDINGS: Two hundred and fourteen patients have been assessed. Forty
      four patients (20.5%) were judged inappropriate for training (n=19) or refused it
      (n=25). Primary perception of the self-injection method showed absence of fear of
      injections among patients in 43.7% of cases. Training was successful in 88% of
      cases. Twenty-one patients out of 170 (12%) gave up after completing the
      training. Questionnaires given at the end of the treatment found a generally
      favourable opinion on self-injections among 73.26% of patients (n=86). Compliance
      was good - 95.5% of patients completed all their injections. Platelet counts were
      considered appropriate only in 52.5% of cases. INTERPRETATION: It seems possible
      to extend the practice of self-injection to other types of injections prescribed
      after discharge from the emergency department, such as preventive low molecular
      weight heparin for surgical or medical purposes and curative ambulatory low
      molecular weight heparin treatment for deep vein thrombosis.

PMID- 16969231
TI  - The practice of pediatric procedural sedation and analgesia in the emergency
      department.
AB  - The treatment of acute pain and anxiety in children undergoing therapeutic and
      diagnostic procedures in the emergency department has improved dramatically over
      the last few years. The availability of noninvasive monitoring devices and the
      use of short-acting sedative and analgesic medications enable physicians to
      conduct safe and effective sedation and analgesia treatment. In today's practice
      of pediatric emergency medicine, sedation and analgesia has been considered as
      the standard of care for procedural pain. The following article describes the
      basic principles of pediatric procedural sedation and analgesia in the emergency
      department.

PMID- 16969232
TI  - Simple thoracostomy in prehospital trauma management is safe and effective: a 2
      year experience by helicopter emergency medical crews.
AB  - OBJECTIVE: To evaluate the effectiveness and potential complications of simple
      thoracostomy, as first described by Deakin, as a method for prehospital treatment
      of traumatic pneumothorax. METHODS: Prospective observational study of all severe
      trauma patients rescued by our Regional Helicopter Emergency Medical Service and
      treated with on-scene simple thoracostomy, over a period of 25 months, from June
      1, 2002 to June 30, 2004. RESULTS: Fifty-five consecutive severely injured
      patients with suspected pneumothorax and an average Revised Trauma Score of 9.6+/
      2.7 underwent field simple thoracostomy. Oxygen saturation significantly improved
      after the procedure (from 86.4+/-10.2% to 98.5%+/-4.7%, P<0.05). No difference
      exists in the severity of thoracic lesions between patients with systolic
      arterial pressure and oxygen saturation below and above or equal to 90. A
      pneumothorax or a haemopneumothorax was found in 91.5% of the cases and a
      haemothorax in 5.1%. No cases of major bleeding, lung laceration or pleural
      infection were recorded. No cases of recurrent tension pneumothorax were
      observed. Forty (72.7%) patients survived to hospital discharge. CONCLUSIONS:
      Prehospital treatment of traumatic pneumothorax by simple thoracostomy without
      chest tube insertion is a safe and effective technique.

PMID- 16969233
TI  - Protective effects of N-acetylcysteine and erdosteine on hemorrhagic shock
      induced acute lung injury.
AB  - BACKGROUND: The drugs N-acetylcysteine and erdosteine were used to evaluate their
      protective effects in hemorrhagic shock-induced acute lung injury in an animal
      model. METHODS: Forty rats were used and randomly allocated into four groups
      (n=10). Animals in group III were fed with water containing 1 mg/dl erdosteine,
      and those in group IV were given 0.5 mg/dl N-acetylcysteine 3 days before the
      experiment. Group I was taken as the control and group II was taken as the
      hemorrhagic shock group. Hemorrhagic shock was initiated by blood withdrawal and
      reduction of the mean arterial pressure to 40 mmHg within 10 min via the right
      carotid artery. After a hypotensive period of 2 h, animals were resuscitated by
      transfusion of the shed blood and Ringer lactate in a volume equal to the shed
      blood. After a period of 1 h, blood samples were taken via the carotid artery.
      Bronchoalveolar lavage was performed to recover cells from the alveolar space
      with 40 ml of bronchoalveolar lavage fluid. Lung tissues were also resected to
      measure tissue malondialdehyde and L-gamma-glutamyl-L-cysteinyl-glycine levels
      with high performance liquid chromatography. The numbers of neutrophils and
      alveolar macrophages in bronchoalveolar lavage fluid were counted. RESULTS: Serum
      malondialdehyde levels were significantly higher in the shock groups (P<0.05),
      but there was no significant difference (P>0.05). Lung malondialdehyde levels
      were also significantly increased in the shock groups (P<0.05). In the erdosteine
      applied group, tissue malondialdehyde levels were lower than in group II and the
      NAC-applied group (P<0.05). In the analyses of serum and lung tissue L-gamma
      glutamyl-L-cysteinyl-glycine, the values of groups I, II and IV were found to be
      below the calibration graphics. The alveolar macrophage count was found to be the
      highest and the neutrophil count the lowest in group III when compared with the
      other groups in bronchoalveolar lavage fluid analyses (P<0.05). CONCLUSION: We
      may say that in the model of hemorrhagic shock-induced acute lung injury, it was
      found that erdosteine has a protective effect on lung tissue.

PMID- 16969234
TI  - Lawnmower injuries in children.
AB  - OBJECTIVE: Power lawnmowers can pose significant danger of injury to both the
      operator and the bystander, from direct contact with the rotary blades or missile
      injury. Our objective was to review our experience with paediatric lawnmower
      associated trauma, and the safety recommendations available to operators of power
      lawnmowers. METHODS: The patient cohort comprised paediatric (<16 years of age)
      patients treated for lawnmower-associated trauma, by the plastic surgery service,
      between 1996 and 2003. These patients were identified retrospectively. Age at the
      time of injury, location and extent of bony and soft tissue injuries sustained,
      treatment instituted and clinical outcome were recorded. Brochures and
      instruction manuals of six lawnmower manufacturers were reviewed, and safety
      recommendations noted. RESULTS: Fifteen patients were identified. The majority of
      injuries occurred from direct contact with the rotary blades (93%); the remaining
      child sustained a burn injury. Fourteen children (93%) required operative
      intervention. Seven patients (46%) sustained injuries resulting in amputation,
      two of whom had major limb amputations. All children, except the burns patient,
      underwent wound debridement and received antibiotic therapy. Reconstructive
      methods ranged from primary closure to free tissue transfer. Many patients
      required multiple procedures. In all instruction manuals, instructions to keep
      children and pets indoors or out of the yard when mowing were found. CONCLUSIONS:
      Lawnmower injuries can be devastating, particularly in children. Many victims
      have lasting deformities as a result of their injuries. Awareness of and
      stringent adherence to safety precautions during use of power lawnmowers can
      prevent many of these accidents.

PMID- 16969235
TI  - Could a computer-based system including a prevalence function support emergency
      medical systems and improve the allocation of life support level?
AB  - OBJECTIVES: To evaluate whether a computer-based decision support system could be
      useful for the emergency medical system when identifying patients with acute
      myocardial infarction (AMI) or life-threatening conditions and thereby improve
      the allocation of life support level. METHODS: Patients in the Municipality of
      Goteborg who dialled the dispatch centre due to chest pain during a period of 3
      months. To analyse the relationship between patient characteristics (according to
      a case record form used during an interview) and the response variables (AMI or
      life-threatening condition), multivariate logistic regression was used. For each
      patient, the probability of AMI/life-threatening condition was estimated by the
      model. We used these probabilities retrospectively to allocate advanced life
      support or basic life support. This model allocation was then compared with the
      true allocation made by the dispatchers. RESULTS: The sensitivity, that is, the
      percentage of AMI patients allocated to advanced life support, was 85.7% in
      relation to the true allocation made by the dispatchers. The corresponding
      sensitivity regarding allocation made by the model was 92.4% (P=0.17). The
      specificity was also slightly higher for the model allocation than the dispatcher
      allocation. Among the 15 patients with AMI who were allocated to basic life
      support by the dispatchers, nine died (eight during and one after
      hospitalization). Among the eight patients with AMI allocated to basic life
      support by the model, only one patient died (in hospital) (P=0.02). CONCLUSION: A
      computer-based decision support system including a prevalence function could be a
      valuable tool for allocating the level of life support. The case record form,
      however, used for the interview can be refined and a model based on a larger
      sample and confirmed in a prospective study is recommended.

PMID- 16969236
TI  - The impact of associated diseases on the etiology, course and mortality in
      geriatric trauma patients.
AB  - OBJECTIVES: To determine the impact of accompanying medical illnesses on the
      cause, course, mortality and morbidity of a geriatric trauma population. METHODS:
      This prospective and observational study was carried out in a university hospital
      that is a level 1 trauma center between January 2002 and January 2003 with a
      total of 55 patient aged over 65 years. All consecutive patients presented with
      trauma and having an Abbreviated Injury Severity Scale (AIS) score greater than
      20 points were recruited. All patients and relatives were requested to give
      information on the accompanying diseases. The raw data were analyzed as to the
      effect of these factors on the findings relating to trauma severity, vital signs,
      course, short-term mortality and morbidity. RESULTS: The most common mechanism of
      trauma was pedestrians hit by cars (33%) in the young elderly group; 81.2% of the
      sample had an associated disease and 40% of these patients had a complaint
      related to the disease. The rates of admission to the intensive care units and
      mortality were higher in patients with higher total Abbreviated Injury Scale
      scores (P=0.007, P=0.003). Patients with pulmonary disease or myocardial
      infarction had a significantly higher mortality rate than those without.
      CONCLUSION: Although not an essential factor in the cause per se, the diseases
      often encountered in the geriatric trauma population have a significant role on
      the course and mortality.

PMID- 16969237
TI  - A case of group A streptococcal meningitis following acute otitis media.
AB  - Group A streptococcal meningitis is less common than other forms of meningitis;
      however, the occurrence of this infection is associated with high mortality and
      morbidity. Early recognition and a prompt treatment are therefore essential. We
      review one case of an Asian women admitted with group A streptococcal meningitis
      as a complication of otitis media.

PMID- 16969238
TI  - Detection of gastric drug packet by ultrasound scanning.
AB  - A 53-year-old male drug user was brought to the emergency department by police
      for suspected drug smuggling by body packing. The abdominal X-ray revealed
      suspicion of the presence of a drug packet in the gastric antrum, but the patient
      strongly denied body packing. Abdominal ultrasonography confirmed the presence of
      a 4.0 x 2.8 cm(2) oval-shaped echogenic mass with posterior shadowing in the
      gastric antrum. A small plastic bag with many blue tablets was later retrieved by
      endoscopy. Ultrasonography is recommended in similar cases with doubtful
      radiological findings.

PMID- 16969239
TI  - Point-of-care blood analyzer during the interhospital transport of critically ill
      children.
AB  - OBJECTIVES: To investigate the influence of point-of-care laboratory results
      (arterial blood gases, ionized calcium, potassium, sodium, glucose, hematocrit
      and hemoglobin) on therapeutic interventions during interhospital pediatric
      intensive care transport. DESIGN: Prospective observational study. SETTINGS:
      Specialist pediatric intensive care retrieval team of a university hospital.
      PARTICIPANTS: Critically ill pediatric patients who were referred from a
      community hospital to a pediatric intensive care of a tertiary center. The
      retrieval team sampled arterial blood during the time of stabilization in the
      referring hospital and during transport. All results were recorded and for each
      result the physician of the specialist retrieval team wrote down the influence on
      the treatment (none, partly, only). The physician specified the kind of
      intervention. RESULTS: Point-of-care blood analyses influenced the therapeutic
      management in 76.5% of all blood samples and in 86.2% of the referred patients.
      Of all interventions, 42.9% were based only on the laboratory results. The
      majority of interventions were adjustments of the mechanical ventilation. Point
      of-care blood analyses reduced the delay in treatment of potentially life
      threatening abnormalities of laboratory results (severe hypokalemia and low
      hematocrit). CONCLUSIONS: During interhospital pediatric intensive care
      transport, point-of-care blood analyses frequently led to therapeutic
      interventions. Some abnormal blood results were potentially life threatening and
      could not have been discovered without point-of-care measurement. We therefore
      recommend the use of a point-of-care blood analyzer during interhospital
      intensive care transports, not only for blood gases but also for electrolytes,
      glucose and hematocrit.

PMID- 16969240
TI  - Prehospital evaluation and treatment of a presumed acute coronary syndrome: what
      are the options?
AB  - The earlier infarct-limiting therapy is started the better is the outcome among
      patients suffering from a threatened myocardial infarction. The introduction of a
      prehospital electrocardiogram has improved triage of patients with acute chest
      pain. With regard to medication, fibrinolytic agents have the best documentation.
      Their use when frequently followed by a percutaneous coronary intervention at a
      later stage may be a good alternative among patients with ST-elevation myocardial
      infarction. Other treatments of potential value in the prehospital setting are
      oxygen, narcotic analgesics, nitrates, aspirin, heparin, low molecular weight
      heparin, glycoprotein IIB, IIIA blockers, clopidogrel and beta-blockers. We need
      further studies, however, for most of these treatments including cost-benefit
      analysis, analysis of various logistic aspects and safety in order to confirm
      their value.

PMID- 16969241
TI  - Blood cultures ordered in the adult emergency department may be useful.

PMID- 16969242
TI  - Urgent emergency issue in Poland.
AB  - The paper refers to the problem of emergency medical service in Poland, which is
      the only European Union Member State not having activated the emergency phone
      number 112. This fact has caused the threat of European Union sanctions. In this
      context, we try to discuss the chances of finalizing reform of the dramatically
      inefficient Polish emergency services. Except for the lack of the integrated
      emergency call centres, there is no appropriate network of emergency hospital
      departments in Poland and no clear regulations concerning emergency professions.
      The necessary law was enacted in 2001, but it did not come into force. The threat
      of European Union sanctions may hasten its implementation; however, the weak
      position of the present government may cause a further delay of the reform.

PMID- 16969243
TI  - Analgesia and sedation in the presence of a naltrexone implant: a novel
      pharmacological challenge.
AB  - In chronic opioid abusers, sedation and analgesia present challenges. We describe
      two trauma patients with naltrexone implants (depot micro-receptor antagonists
      that facilitate opioid withdrawal) requiring intensive care. The first patient, a
      28-year-old man, sustained chest and pelvic injuries when hit by a motor vehicle.
      When we learned of the implant he was already on a morphine infusion, appearing
      responsive to it. It subsequently emerged that the implant was placed 3 months
      earlier, but had only a 6-week duration of effect and had expired. His intensive
      care course was unaffected. The second patient, a 24-year-old man, had been
      stabbed in the chest. His implant being recently placed, he was markedly opioid
      insensitive. Propofol, tramadol and paracetamol proved effective. We wish to
      notify colleagues of the existence of these implants as they are increasingly
      widely used, and should be considered when encountering severe opioid resistance.
      Secondly, their role in managing opioid-dependent physicians appears promising.

PMID- 16969244
TI  - Spanish Broom flower ingestion: a very unusual poisoning.

PMID- 16969245
TI  - Hypoglycaemia in patients with diabetes: do they prefer prehospital treatment or
      admission to hospital?

PMID- 16969246
TI  - Quality improvement as research: unintended consequences and the slippery slope.

PMID- 16969248
TI  - Diffusion of the clinical nurse leader innovation.

PMID- 16969249
TI  - Collaboration is a competency!

PMID- 16969250
TI  - Patients' perceptions of today's nursing attire: exploring dual images.
AB  - OBJECTIVE: To determine what image is conveyed to patients by 3 different nurse
      uniforms. BACKGROUND: With the shift from the historical "single note" white
      nursing uniform to the current cacophony of uniforms, it is difficult to
      recognize the registered nurses. Uniforms are nonverbal messages sent to
      patients, making it critical to know what images patients associate with
      different uniforms. METHODS: One hundred eighty patients (convenience sample) in
      a Pacific Northwest hospital completed a 13-item survey asking for perceptions of
      3 nursing uniforms. Participants selected 1 of 3 nurse uniform photos that best
      reflected each of 10 characteristics and 3 overall images. RESULTS: Using
      descriptive statistics and multivariate analyses, 2 themes for images emerged;
      the first is described professional and the second, approachable. When
      demographic variables were included, 4 generational-age strata yielded these same
      themes. However, different uniforms were selected for the various characteristics
      by age. Patients in the Seniors category consistently chose the white uniform for
      both themes, whereas Generations X, Y, and Baby-Boomers chose a uniform with a
      print as being approachable. CONCLUSION: The dual images of nursing present a
      challenge for nursing leaders deciding whether uniforms should be standardized
      for nursing staff. Complicating this issue are differences in perceptions among
      the 4 generational ages.

PMID- 16969251
TI  - Crew resource management: applications in healthcare organizations.
AB  - Healthcare organizations continue their struggle to establish a culture of open
      communication and collaboration. Lessons are learned from the aviation industry,
      which long ago acknowledged that most errors were the result of poor
      communication and coordination rather than individual mistakes. The author
      presents a review of how some healthcare organizations have successfully adopted
      aviation's curriculum called Crew Resource Management, which promotes and
      reinforces the conscious, learned team behaviors of cooperation, coordination,
      and sharing.

PMID- 16969252
TI  - The impact of culture change on nurse retention.
AB  - Given the nursing shortage, retaining qualified nurses is of primary importance
      to nurse executives. In this article, the authors discuss problems they
      experienced in retaining newly hired nurses on 3 surgical nursing units and
      describe how efforts to change the culture of the units resulted in dramatic
      improvements in nurse satisfaction and the retention of new hires.

PMID- 16969253
TI  - Nurse staffing, nursing intensity, staff mix, and direct nursing care costs
      across Massachusetts hospitals.
AB  - OBJECTIVE: This study describes the distribution of patient-to-registered nurse
      (RN) ratios, RN intensity of care, total staff intensity of care, RN to total
      staff skill mix percent, and RN costs per patient day in 65 acute community
      hospitals and 9 academic medical centers in Massachusetts. METHODS: We conducted
      a retrospective secondary analysis of the Patients First database published by
      the Massachusetts Hospital Association for planned nurse staffing in 601
      inpatient nursing units in the state for 2005 using a multivariate linear
      statistical model controlling for hospital type and unit type. Nursing unit types
      were identified as adult and pediatric medical/surgical, step down, critical
      care, neonatal level II, and neonatal level III/IV nurseries. RESULTS: Medical
      centers had significantly higher case-mix index (1.72 vs 1.20, P < .001), longer
      lengths of stay (5.18 vs 4.19, P < .001), more beds (574 vs 147, P < .001),
      discharges (31,597 vs 7,248, P < .001), and patient days (161,440 vs 31,020, P <
      .001) compared with to community hospitals. Medical centers had significantly
      lower patient-to-RN ratios (3.22 vs 4.64, P < .001), higher nursing intensity and
      total nursing staff intensity (9.62 vs 7.43/11.75 vs 9.87, both P < .001), higher
      percent of RN to all staff mix (79% vs 71%, P < .001), and higher RN costs per
      patient day ($385 vs $297, P < .001) compared with to community hospitals. There
      were significant differences in adult med/surg units between community hospitals
      and medical centers for patient-to-RN staffing ratios (5.25 vs 4.08), nursing
      intensity (5.1 vs 6.2 hours daily), skill mix (67% vs 73% RN), and RN costs per
      patient day ($203 vs $248, all P < .001). There were no significant differences
      between the adult step-down units. CONCLUSION: The significant differences
      between community hospitals and medical centers, unit type, as well as the high
      degree of variability in patient-to-RN ratios, nursing intensity, skill mix, and
      RN costs per patient day suggest that nursing resource expenditure at
      Massachusetts hospitals is complex and affected by case mix, unit size, and
      complexity of care.

PMID- 16969254
TI  - The benefits of standardized nursing languages in complex adaptive systems such
      as hospitals.
AB  - Paperwork is a major source of frustration for hospital nurses and takes valuable
      time away from patient care. Studies indicate that nurses spend an estimated 13%
      to 28% of total shift time documenting. The growth in documentation requirements
      for nurses can, in part, be attributed to an exponential rise in health system
      complexity. Authors explore the documentation of nursing care plans from a
      complex adaptive system perspective and then analyze the utility of adopting a
      standardized nursing language. An actual case history of a nursing unit's attempt
      to reduce complexity, improve completion time, and increase staff satisfaction in
      care planning by adopting a standardized nursing language is provided to
      emphasize a practical application.

PMID- 16969255
TI  - Practical and clinical benefits of radioimmunotherapy lead to advantages in cost
      effectiveness in the treatment of patients with non-Hodgkin's lymphoma.

PMID- 16969256
TI  - Nuclear medicine imaging of diabetic foot infection: results of meta-analysis.
AB  - BACKGROUND AND AIM: Osteomyelitis of the foot is the most commonly encountered
      complication in diabetic patients. Nuclear medicine techniques are usually
      complementary to radiology in the diagnosis of foot infections; they play an
      important role in various clinical situations. The aim of this study was to
      develop a practical guideline to describe the radiopharmaceuticals to be used for
      different clinical conditions and different aims in diabetic foot infection.
      METHODS: In this study, we reviewed 57 papers (published between 1982 and 2004;
      50 original papers and seven reviews) that described the imaging of the diabetic
      foot and examined a total of 2889 lesions. We performed data analysis to
      establish which imaging technique could be used as a 'gold standard' to diagnose
      infection, evaluate the extent of disease and monitor the efficacy of therapy.
      RESULTS AND CONCLUSION: We provide a guideline to assist in the selection of the
      optimal radiopharmaceuticals for different clinical conditions and different
      aims.

PMID- 16969257
TI  - The influence of attenuation correction and reconstruction techniques on the
      detection of hypo-perfused lesions in brain SPECT images.
AB  - BACKGROUND: We evaluated the effects of attenuation correction and reconstruction
      techniques on the detection of hypoperfused lesions in brain SPECT imaging.
      METHODS: A software phantom was constructed using the data available on the
      BrainWeb database by assigning activity values to grey and white matter. The true
      attenuation map was generated by assigning attenuation coefficients to six
      different tissue classes to create a non-uniform attenuation map. The uniform
      attenuation map was calculated using an attenuation coefficient of 0.15 cm(-1).
      Hypoperfused lesions of varying intensities and sizes were added. The phantom was
      then projected as typical SPECT projection data, taking into account attenuation
      and collimator blurring with the addition of Poisson noise. The projection data
      were reconstructed using four different methods: filtered back-projection in
      combination with Chang's first-order attenuation correction using the uniform or
      the true attenuation map and maximum likelihood iterative reconstruction using
      the uniform or the true attenuation map. Different Gaussian post-smoothing
      kernels were applied onto the reconstructed images and the performance of each
      procedure was analysed using figures of merit such as signal-to-noise ratio, bias
      and variance. RESULTS: Uniform attenuation correction offered only slight
      deterioration of the signal-to-noise ratio compared to the true attenuation map.
      Maximum likelihood produced superior signal-to-noise ratios and lower bias at the
      same variance in comparison to the filtered back-projection. CONCLUSION: Uniform
      attenuation correction is adequate for lesion detection while maximum likelihood
      provides enhanced lesion detection when compared to filtered back-projection.

PMID- 16969258
TI  - Evaluation of transcriptional activity of the oestrogen receptor with sodium
      iodide symporter as an imaging reporter gene.
AB  - BACKGROUND: Oestrogen receptors are ligand-dependent transcription factors whose
      activity is modulated either by oestrogens or by an alternative signalling
      pathway. Oestrogen receptors interact via a specific DNA-binding domain, the
      oestrogen responsive element (ERE), in the promoter region of sensitive genes.
      This binding leads to an initiation of gene expression and hormonal effects.
      OBJECTIVE: To determine the transcriptional activity of the oestrogen receptor,
      we developed a molecular imaging system using sodium iodide symporter (NIS) as a
      reporter gene. METHODS: The NIS reporter gene was placed under the control of an
      artificial ERE derived from pERE-TA-SEAP and named as pERE-NIS. pERE-NIS was
      transferred to MCF-7, human breast cancer cells, which highly expressed oestrogen
      receptor-alpha with lipofectamine. Stably expressing cells were generated by
      selection with G418 for 14 days. After treatment of 17beta-oestradiol and
      tamoxifen with serial doses, the (125)I uptake was measured for the determination
      of NIS expression. The inhibition of NIS activity was performed with 50 micromol
      x l(-1) potassium perchlorate. RESULTS: The MCF7/pERE-NIS treated with 17beta
      oestradiol accumulated (125)I up to 70-80% higher than did non-treated cells. NIS
      expression was increased according to increasing doses of 17beta-oestradiol.
      MCF7/pERE-NIS treated with tamoxifen also accumulated (125)I up to 50% higher
      than did non-treated cells. Potassium perchlorate completely inhibited (125)I
      uptake. When MDA-MB231 cells, the oestrogen receptor-negative breast cancer
      cells, were transfected with pERE-NIS, (125)I uptake of MDA-MB-231/pERE-NIS did
      not increase. CONCLUSION: This pERE-NIS reporter system is sufficiently sensitive
      for monitoring transcriptional activity of the oestrogen receptor. Therefore, cis
      enhancer reporter systems with ERE will be applicable to the development of a
      novel selective oestrogen receptor modulator with low toxicity and high efficacy.

PMID- 16969259
TI  - Evaluating dopamine transporter activity with 99mTc-TRODAT-1 SPECT in drug-naive
      Tourette's adults.
AB  - OBJECTIVES: Findings on imaging of dopamine transporter (DAT) activity in
      patients with Tourette's syndrome remain inconclusive. The present study was
      carried out to observe DAT activity in patients with well-controlled Tourette's
      syndrome by using (99m)Tc-TRODAT-1 single photon emission computerized tomography
      (SPECT). METHODS: Six drug-naive patients with Tourette's syndrome (mean age+/
      SD, 21.2+/-1.5 years) were recruited. All met the criteria for Tourette's
      syndrome established in the DSM-IV. Seventeen age-matched and sex-matched healthy
      subjects served as the controls. Brain SPECT were acquired 165-195 min after
      administrating 740 MBq of (99m)Tc-TRODAT-1, using a double-headed camera equipped
      with ultra-high-resolution fan-beam collimators. The specific uptake ratio was
      calculated by subtracting the mean counts per pixel in the occipital cortex from
      the mean counts per pixel in the striatum, putamen or caudate nucleus and by
      dividing the result by the mean counts per pixel in the occipital cortex. Tic
      severity scores were also measured and correlated with the specific uptake
      ratios. RESULTS: No significant difference in DAT activity between patients with
      Tourette's syndrome and control subjects was found in the striatum and its sub
      regions. Tic-severity scores were also not correlated with specific uptake ratios
      measured from the striatum and its sub-regions. CONCLUSIONS: In conjunction with
      previous findings, our results suggested that functional abnormality of the
      dopamine system in patients with Tourette's syndrome might be evident only in its
      early stage. Adaptation to tic symptoms might play a role in regulating the
      neural system.

PMID- 16969260
TI  - Is it possible to refine the indication for sentinel node biopsy in high-risk
      ductal carcinoma in situ?
AB  - BACKGROUND: The indication for sentinel node biopsy (SNB) has not been fully
      established yet for patients with ductal carcinoma in situ (DCIS). AIM: To relate
      the conversion rate to invasive carcinoma with sentinel node positivity in high
      risk DCIS, and to refine the clinical presentation analysis in order to better
      select patients for SNB. For this purpose, a risk score was devised. METHODS:
      From 1998 to 2005, 151 high-risk DCIS patients from six clinical centres were
      included in a prospective sentinel node database. The conversion rate to invasive
      carcinoma was 39%. Ten of 142 (7%) successful SNBs showed a positive sentinel
      node (eight micrometastatic). The sentinel node was positive in 1% of pure DCIS,
      in 5.5% of DCIS with micro-invasion, and in 19.5% of invasive carcinoma. RESULTS:
      Both clinical presentation and corresponding risk score were closely related to
      conversion to invasive carcinoma. The association of risk score and sentinel node
      positivity approached but did not reach statistical significance (P=0.06);
      therefore a subset of further selected higher risk patients could not be defined.
      CONCLUSION: The relevance of SNB positivity cannot be overlooked in high-risk
      DCIS patients, however, because SNB is not free from morbidity and cost, more
      studies are needed to refine its final indication.

PMID- 16969261
TI  - Myocardial perfusion quantification in patients suspected of cardiac syndrome X
      with positive and negative exercise testing: a [13N]ammonia positron emission
      tomography study.
AB  - BACKGROUND: The combination of angina pectoris, angiographically normal coronary
      arteries, and a positive exercise stress test (EST) is referred to as cardiac
      syndrome X. However, a large group of patients suspected of syndrome X reveals a
      normal exercise stress test and weakens the diagnosis of syndrome X. Previous
      studies demonstrated an impaired coronary flow reserve on ammonia positron
      emission tomography (PET) in patients with syndrome X. AIM: To evaluate the
      coronary flow reserve in patients suspected of syndrome X with positive and
      negative EST findings, using [(13)N]ammonia PET as the diagnostic aid. METHODS:
      Forty-two patients with chest pain and a normal coronary angiography, were
      analysed by exercise stress testing (EST) and the dypyridamole stress test (DST)
      on [(13)N]ammonia PET. Two subgroups were predefined, based on outcome of EST: an
      EST positive and negative group. A normal control group was used as the reference
      method. RESULTS: A total of 24 (57%) out of 42 patients had significant ST-T
      changes (EST positive). [(13)N]ammonia PET showed a significantly lower rest flow
      in the EST positive and EST negative group compared to controls (P<0.001 and
      P=0.0028, respectively). DST [(13)N]ammonia PET perfusion was significantly
      reduced in flow in both the EST positive and EST negative groups (P<0.001 both),
      as was the DST/rest [(13)N]ammonia perfusion reserve (P<0.001 for both), compared
      to normal controls. CONCLUSION: PET demonstrates a reduced coronary flow reserve
      in patients suspected of syndrome X, irrespective of the EST findings.

PMID- 16969262
TI  - 18F-FDG PET and PET/CT for detection of pulmonary metastases from musculoskeletal
      sarcomas.
AB  - OBJECTIVE: Sarcomas represent a significant therapeutic challenge and their
      potential for distant pulmonary metastases is well known.
      [(18)F]Fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) has a
      role in differentiating sarcomas from benign tumours and assessing the response
      to therapy in advanced sarcomas. However, PET appears to be less accurate in
      detection of pulmonary metastases. We were therefore prompted to review our
      experience with PET and PET/computed tomography (CT) in osseous and soft tissue
      sarcomas (OSTSs). METHODS: This is a retrospective study (January 1995 to
      December 2004) of 106 patients with histological diagnosis of OSTS, who had PET
      and PET/CT at our institution. The group included 52 men and 54 women, aged 12-92
      years (average, 45+/-20 years). RESULTS: For all the patients in the analysis,
      the sensitivity and specificity were 68.3% (95% CI: 53-80.4) and 98.4% (95% CI:
      91.8-99.7) for PET, with 95.1% sensitivity (95% CI: 83.8-98.6) and 92.3%
      specificity (95% CI: 83.2-96.7) for CT. Pulmonary metastases were seen in 40
      patients. CT identified 17 lesions larger than 1.0 cm, while PET identified 13 of
      them (76.5%). CONCLUSIONS: Chest CT is more sensitive than PET in detecting
      pulmonary metastases from OSTS. A significant portion of known pulmonary
      metastases greater than 1.0 cm on CT, are PET negative. Sub-centimetre CT lesions
      should not be considered false positive if inactive on PET. A negative PET scan
      in the presence of suspicious CT findings in the chest cannot reliably exclude
      pulmonary metastases from OSTS.

PMID- 16969263
TI  - The ratio of the apex/anterior wall: a marker of breast attenuation artifact in
      women.
AB  - BACKGROUND: Breast attenuation artifact is well known for reducing the accuracy
      of myocardial perfusion imaging in women. We have noticed the particular pattern
      of relative preservation of apical activity in women with breast attenuation and
      decreased anterior wall counts. This study was undertaken to see if this finding
      could be used to improve the accuracy of perfusion imaging in women. METHODS: We
      identified 295 women referred for exercise stress testing using (201)Tl single
      photon emission computed tomography (SPECT) of whom 193 had less than 5%
      probability of coronary disease and 102 had coronary artery disease documented by
      catheterization within 60 days of stress testing (mean of 1.8+/-0.8 vessels
      with=50% stenosis). Patients with documented myocardial infarction, pathologic Q
      waves, left bundle branch block, non-ischaemic cardiomyopathy or prior bypass
      grafting were excluded. Volume-weighted bullseye plots were generated and
      normalized to 100; next, regions of interest were drawn over the anterior wall
      and apex in all patients and the ratio of the mean counts of each region was
      calculated. The normals were further divided into those with breast attenuation
      (defined as mean anterior counts <70% maximum) and those without. Defect scores
      of all patients were calculated; a formula to adjust the score for patients with
      breast attenuation was developed. Accuracy was assessed by calculating the area
      under the receiver operating curve. RESULTS: The normals, overall, had a mean
      ratio of 1.0+/-0.08 vs. 0.9+/-0.16 for those with coronary disease (P<0.0001). In
      normals with breast attenuation the ratio was 1.1+/-0.08 compared to 0.99+/-0.07
      (P<0.0001) without. By adjusting the anterior wall defect score in patients with
      apex/anterior ratio >1 we were able to improve the accuracy from 0.808+/-0.028 to
      0.826+/-0.027 (P<0.01). CONCLUSIONS: A ratio of the apex to the anterior wall >1
      is not physiological and suggests the presence of significant breast attenuation
      artifact. This finding can be used to produce a small but statistically
      significant improvement in the accuracy of quantitative thallium SPECT in women
      who have not undergone coronary bypass grafting.

PMID- 16969264
TI  - A method for quantitative cell tracking using SPECT for the evaluation of
      myocardial stem cell therapy.
AB  - PURPOSE: A promising SPECT-based method for evaluating stem cells therapy uses
      (111)In-labelled cells, transfected with a reporter gene. Cells are first
      transplanted to the infarct, and subsequently interrogated for transgenic
      expression using a systemic injection of an (131)I-labelled reporter probe. The
      method is impeded by the physical effects of scatter, (131)I/(111)In cross-talk,
      and attenuation. We hypothesize that correcting for physical effects improves
      detection of transgenic expression in transplanted cells when (111)In
      localization is available. METHODS: Canine bone marrow mesenchymal cells (BMMCs),
      radiolabelled and transfected, were injected into infarcted myocardium. Next, a
      reporter probe was injected systemically, and 22 SPECT scans were acquired over
      20 h. Finally, (99m)Tc-sestamibi was injected and imaged. The animal was killed,
      the heart sectioned, and counted for (131)I and (111)In in a well-counter ('gold
      standard'). Canine SPECTs were reconstructed in two ways: with corrections for
      physical effects and without corrections. The first (111)In reconstruction and
      the (99m)Tc reconstruction were used to define volumes-of-interest over the
      transplanted BMMC (VBMMC) and normal myocardium (VNM), respectively. RESULTS:
      (131)I reconstructions without corrections for physical effects had negligible
      differential uptake. With corrections, VBMMC was consistently higher than VNM,
      demonstrating transgene expression. (131)I had the following VBMMC:VNM activity
      ratio: without correction for physical effects=0.869; with corrections=1.23; and
      well-counter=1.21. VNM showed the following (131)I:(111)In activity ratio:
      without corrections=3.07; with corrections=1.38; and well-counter=1.58.
      CONCLUSIONS: In dual-isotope SPECT, corrections for physical effects were
      required to detect transgene expression in cells transplanted into an infarction
      when localization information was available.

PMID- 16969265
TI  - Attenuation-corrected 99mTc-MIBI SPECT in overweight patients with chronic
      ischaemic dysfunction: a comparison to NH3 PET and implications for the diagnosis
      of myocardial viability.
AB  - OBJECTIVE: We determined the value of attenuation correction (AC) of myocardial
      perfusion estimation with (99m)Tc-MIBI SPECT in overweight patients by comparison
      of uncorrected (filtered back-projection (FBP) and corrected (an iterative
      algorithm with a measured attenuation coefficients map (FL-AC)) (99m)Tc-MIBI
      relative uptake to perfusion data obtained in the same patients with NH3 PET. In
      addition, the impact of attenuation correction for the assessment of myocardial
      viability with (99m)Tc-MIBI SPECT was determined using FDG PET as the reference
      method. METHODS: Thirty consecutive overweight patients (BMI=28+/-4) with left
      ventricular dysfunction underwent a resting (99m)Tc-MIBI SPECT and a PET study
      (NH3 and FDG). (99m)Tc-MIBI SPECT scans were reconstructed without attenuation
      correction (FBP) and with attenuation correction (FL-AC). The left ventricle was
      divided into 16 segments, in which the relative uptake was quantified using
      circumferential profiles. A relative uptake > or = 60% was considered consistent
      with viable myocardium for FDG and MIBI. RESULTS: The absolute difference between
      (99m)Tc-MIBI SPECT and NH3 PET uptakes was less pronounced in the inferior (12+/
      10% vs. 17+/-12%, P<0.001), anteroseptal (12+/-11% vs. 16+/-12%, P=0.009) and
      septal (15+/-12% vs. 18+/-14%, P=0.003) regions (FL-AC vs. FBP, respectively).
      The sensitivity of MIBI for diagnosing myocardial viability increased from 83 to
      100% (P=0.034), without loss in specificity. CONCLUSION: Attenuation correction
      improves myocardial perfusion estimation by (99m)Tc-MIBI SPECT in the inferior,
      anteroseptal and septal regions and increases its sensitivity for the diagnosis
      of myocardial viability.

PMID- 16969266
TI  - Comparison of multi-ray and point-spread function based resolution recovery
      methods in pinhole SPECT reconstruction.
AB  - BACKGROUND AND OBJECTIVES: Statistical reconstruction methods allow resolution
      recovery in tomographic reconstruction. Even though resolution recovery has the
      potential to improve overall image quality, pinhole SPECT images are still often
      reconstructed using simplified models of the acquisition geometry in order to
      reduce reconstruction time. This paper investigates the benefits of two
      resolution recovery methods, multi-ray and point-spread function based, in
      pinhole SPECT by comparing them to uncorrected reconstruction. METHODS:
      Resolution recovery was incorporated into ordered subsets expectation
      maximization reconstruction algorithm. The first of the correction methods used a
      simple but very fast multiple projection ray approach, whereas the second, much
      slower, method modelled the acquisition geometry more accurately using the
      analytical point-spread function of the pinhole collimator. Line source, Jaszczak
      and contrast phantom studies were performed and used for comparison. RESULTS:
      Resolution recovery improved resolution, contrast and visual quality of the
      images when compared to reconstructions without it. The method based on the point
      spread function performed slightly better, but was almost 50 times slower than
      the much simpler multi-ray approach. CONCLUSION: The multiple projection ray
      approach is a promising method for very fast and easy resolution recovery in
      pinhole SPECT. It has a profound effect on image quality and can markedly improve
      the resolution-sensitivity trade-off.

PMID- 16969268
TI  - Norepinephrine transporter polymorphisms in Tourette syndrome with and without
      attention deficit hyperactivity disorder: no evidence for significant
      association.
AB  - Noradrenergic abnormalities have been proposed in the pathophysiology of Tourette
      syndrome and attention-deficit hyperactivity disorder. Patients with Tourette
      syndrome with (n=115) and without (n=110) attention-deficit hyperactivity
      disorder were evaluated for association with two single nucleotide polymorphisms
      of the norepinephrine transporter gene (SLC6A2); a T-182C single nucleotide
      polymorphism located in the 5' flanking promoter region and a silent mutation
      (G1287A) occurring in exon 9. A polymerase chain reaction restriction enzyme
      assay was developed for the T-182C single nucleotide polymorphism based on a
      prior sequencing methodology. In this case-control study, no association was
      identified between either polymorphism and Tourette syndrome or attention-deficit
      hyperactivity disorder. In a small subset, these NET polymorphisms did not
      predict therapeutic response to the noradrenergic transporter inhibitor
      atomoxetine. Further research with additional NET polymorphisms and larger sample
      sizes are indicated in the pursuit of biomarkers for therapeutic responders.

PMID- 16969269
TI  - Catechol-O-methyltransferase gene variants in mood disorders in the Italian
      population.
AB  - Dysfunctions of dopaminergic transmission have been implicated in the
      pathogenesis of mood disorders and variants at the catechol-O-methyltransferase
      (COMT) gene have been recently reported to be associated with bipolar disorder.
      In this study, we tried to replicate this finding in an independent sample of
      participants affected by mood disorders. Eight hundred and five psychiatric in
      patients affected by bipolar (n=446) and major depressive (n=359) disorder were
      included. All patients and 116 controls were typed for the COMT variants using
      polymerase chain reaction techniques. A subsample of 458 patients was assessed
      for their lifetime symptomatology. The sample was analyzed alone and pooled with
      111 participants and 127 controls collected in the center of Pisa and previously
      reported. COMT variants were not associated with mood disorders in our sample, a
      trend was observed toward an excess of COMT*A allele in the pooled sample. The
      analysis of symptomatology factors did not show any significant difference as
      well. Possible stratification factors such as sex, current age and age of onset
      did not affect the observed results. Control subjects from the two centers showed
      a similar genotype distribution. In conclusion, COMT variants were not a major
      liability factor for mood disorder and for mood disorder symptomatology in the
      present sample; however, we could not subdivide our sample on the basis of panic
      comorbidity as in the original paper and this could be considered a possible
      reason for the discrepant finding.

PMID- 16969270
TI  - No association between genetic variants at the GRIN1 gene and bipolar disorder in
      a German sample.
AB  - Disturbed glutamatergic neurotransmission has been implicated in the pathogenesis
      of schizophrenia and bipolar disorder, with the N-methy-D-aspartate receptors
      being in the focus of research. The NR1 subunit, which is encoded by the gene
      GRIN1, plays a key role in the functionality of N-methy-D-aspartate receptors. We
      tested the association between GRIN1 and bipolar disorder in a sample of German
      descent, consisting of 306 bipolar disorder patients and 319 population-based
      controls. No significant association was found. In accordance with our recent
      findings, we hypothesized that restricting case definition to individuals with a
      history of persecutory delusions might clarify the relationship between bipolar
      disorder and GRIN1. This stratified analysis did not yield any significant
      association either. Our results do not support an association of the GRIN1 gene
      with bipolar disorder in the German population.

PMID- 16969271
TI  - Association study of adenosine A2a receptor (1976C>T) genetic polymorphism and
      mood disorders and age of onset.
AB  - Evidence suggests that the adenosine A2a receptor (A2aAR) may be implicated in
      the pathogenesis of mood disorders. We tested the hypothesis that the A2aAR
      1976C>T genetic variant confers susceptibility to mood disorders by comparing 192
      mood disorder patients and 216 normal controls. The distribution of the A2aAR
      genotypes and alleles did not differ significantly comparing the two groups,
      suggesting that it is unlikely that the A2aAR 1976C>T polymorphism plays a major
      role in the development of mood disorders.

PMID- 16969272
TI  - Serotonin transporter gene promoter (5-HTTLPR) and intron 2 (VNTR) polymorphisms:
      a study on Slovenian population of suicide victims.
AB  - Several studies have been carried out to investigate how genetic variants of gene
      encoding for the serotonin transporter (5-HTT) may confer susceptibility to
      suicide. It was demonstrated that polymorphisms in the promoter region (5-HTTLPR)
      and in the second intron (VNTR) have functional consequences and are for this
      reason of particular interest in relation to various psychiatric disorders. In
      our study, we analyzed 5-HTTLPR and VNTR polymorphisms in 235 suicide victims and
      233 controls in a Slovenian population to find a possible association of the
      polymorphisms and suicidal behavior. No statistically important differences
      between genotypes of controls and suicide group (5-HTTLPR: Pearson's chi2=1.597,
      df=2, P=0.455; VNTR: Pearson's chi=1.961, df=4, P=0.744), as well as no
      differences in allele distribution (5-HTTLPR: Pearson's chi2=0.598, df=1,
      P=0.467; VNTR: Pearson's chi2=0.837, df=2, P=0.654) were found, although a
      slightly higher frequency of LL genotype and of L allele was observed in the
      suicide group. Haplotype frequency analysis showed no excess of particular
      haplotypes between the two groups. Our study showed no association of serotonin
      transporter polymorphisms and suicide. The study, however, was performed on a
      population with a very high suicide rate (27.1 victims/100,000 citizens) and the
      role of 5-HTTLPR polymorphisms may be different in other populations.

PMID- 16969273
TI  - No association between polymorphisms in the prostate apoptosis factor-4 gene and
      cocaine dependence.
AB  - OBJECTIVE: A number of studies have investigated the genes underlying dopamine,
      serotonin, and glutamine neurotransmitter systems in order to find a genetic
      basis for the pathology of cocaine dependence. The gene that encodes the prostate
      apoptosis factor-4 (Par-4) protein is located in the 12q21 region and has been
      shown to directly interact with the D2 dopamine receptor and through such
      interaction is thought to directly affect the activity of D2 receptors. The aim
      of this study is to investigate whether polymorphisms in the human Par-4 gene
      contribute to the etiology of cocaine dependence. METHODS: To test this
      hypothesis, we used a case-control design in which the genotype and allele
      frequencies for five single nucleotide polymorphisms in the human Par-4 gene were
      compared between cocaine-dependent individuals (n=172) and controls (n=92) of
      African descent. RESULTS: The genotype results failed to detect any associations
      between polymorphisms in the Par-4 gene and the cocaine-dependent phenotype.
      CONCLUSIONS: The results of this study suggest that variations in the human Par-4
      gene are unlikely to play a major role in the pathophysiology of cocaine
      dependence. This study, however, should be repeated in larger cocaine-dependent
      and control populations to determine that this is indeed the case.

PMID- 16969274
TI  - No evidence for association between NOTCH4 and schizophrenia in a large family
      based and case-control association analysis.
AB  - OBJECTIVES: An analysis of 80 British parent-offspring trios by Wei and Hemmings
      in 2000 revealed thre1e out of five markers within the NOTCH4 locus to be
      strongly associated with schizophrenia. In our present study, we have examined
      NOTCH4 markers in large samples of German and Palestinian-Arab origin. METHODS:
      Our study population comprised a German case-control sample (n=512 schizophrenia
      patients and n=232 controls) and two independent parent-offspring trio samples of
      German (n=159 trios) and Palestinian-Arab (n=208 trios) descent. We examined a
      total of ten single nucleotide polymorphisms within the NOTCH4 locus and the
      adjacent loci, spanning a region of approximately 100 kb. RESULTS: Neither single
      marker nor haplotype analyses showed association with schizophrenia. In addition,
      analyses of the German case-control and trio samples revealed no significant
      association between NOTCH4 polymorphisms and early-onset schizophrenia.
      CONCLUSIONS: Our results suggest that NOTCH4 is unlikely to play a major role in
      the genetic predisposition to schizophrenia in the German or the Palestinian-Arab
      population.

PMID- 16969275
TI  - Association of catecholamine-O-methyltransferase and 5-HTTLPR genotype with
      eating disorder-related behavior and attitudes in females with eating disorders.
AB  - OBJECTIVE: There is growing evidence, that genetic variants contribute to the
      pathogenesis of anorexia nervosa and bulimia nervosa. Genetic studies have
      revealed candidate genes, but no satisfactory associations with the disorders
      have been found so far. The aim of the present study was to evaluate, whether
      behavioral and attitudinal traits of the disorders can serve as phenotypes with a
      possible association with two common functional polymorphisms of the
      monoaminergic pathways. METHOD: Forty-five female in-patients of a specialized
      hospital for eating disorders were included into the study. Eating disorder
      symptomatology was assessed using the Eating Disorder Inventory-2. The functional
      catecholamine-O-methyltransferase (COMT) 158 Val-->Met polymorphism and the
      deletion/insertion polymorphism of the serotonin transporter promoter 5-HTTLPR
      were determined. RESULTS: Carriers of at least one Met-allele of the COMT gene
      had significantly higher total scores of the Eating Disorder Inventory-2, as well
      as significantly higher scores on the subscales bulimia, ineffectiveness,
      interoceptive awareness, maturity fears and impulse regulation. Carriers of the
      deletion of the 5-HTTLPR had significantly higher scores on the subscales drive
      for thinness and body dissatisfaction. CONCLUSION: We found associations between
      the COMT and the 5-HTTLPR polymorphisms and specific clinical, behavioral and
      attitudinal traits of eating disorders. These polymorphisms may predispose their
      carriers to exhibit certain symptoms of eating disorders or confer a general risk
      for more severe forms of these disorders.

PMID- 16969276
TI  - No allelic association or interaction of three known functional polymorphisms
      with bipolar disorder in a northern Swedish isolated population.
AB  - Most genetic association studies in bipolar disorder have focussed on genes
      involved in major neurotransmitter systems or brain development. Functional
      polymorphisms in the serotonin transporter (5-HTTLPR), catechol-O
      methyltransferase (Val158Met) and dopamine D3 receptor (Ser9Gly) genes have all
      been associated with bipolar disorder. We aimed at investigating whether these
      functional variants contribute to the genetic etiology of bipolar disorder in a
      northern Swedish isolated population. Moreover, we wanted to gain information
      about the synergistic contribution of these functional variants. Neither of these
      functional polymorphisms was associated with bipolar disorder in the northern
      Swedish patient-control sample nor did we find evidence of gene-gene interaction.
      Together, our data suggest that these functional variants are not involved in the
      etiology of bipolar disorder in the northern Swedish population nor did gene-gene
      interaction analysis support a central role of these variants in bipolar
      disorder.

PMID- 16969277
TI  - The high-activity Val allele of the catechol-O-methyltransferase gene predicts
      greater cognitive deterioration in patients with psychosis.
AB  - The objective of this study was to examine whether the functional genetic
      polymorphism Val158Met in the catechol-O-methyltransferase (COMT) gene influences
      cognitive deterioration in a sample of patients with psychosis under treatment
      with atypical antipsychotics. Eighty-seven patients with psychosis were genotyped
      for this polymorphism and were assessed with three Wechsler Adult Intelligence
      Scale (WAIS)-III subtests (Vocabulary, Information, and Digit Symbol-Coding).
      Performance on these three subtests was used to compute a 'cognitive
      deterioration index', and the effect of COMT genotype on this cognitive
      deterioration index was examined. A linear relationship between the number of Val
      alleles and the score on the cognitive deterioration index (i.e. the more Val
      alleles, the more cognitive deterioration) was observed. These results confirm
      the role of COMT genotype in the cognition of patients under treatment for
      psychosis, suggesting that it influences the extent of their cognitive
      deterioration.

PMID- 16969278
TI  - No association between the CNTF null mutation and schizophrenia or personality.
AB  - The ciliary neurotrophic factor (CNTF) is a neurotrophic cytokine that plays a
      critical role in neurodevelopment. On the basis of neurodevelopmental hypothesis,
      the CNTF gene has been a candidate locus for schizophrenia. Several studies have
      investigated the association between the null mutation of the gene and
      schizophrenia, however, with inconsistent results. In the present study, we
      investigated the association in 222 Japanese patients with schizophrenia and 237
      controls. The association between the mutation and personality traits was also
      studied, to investigate the effect of the mutation in participants from the
      general population. As a result, no association was observed between the mutation
      and schizophrenia nor personality traits, evaluated by using the Revised NEO
      Personality Inventory scores. The present study did not provide evidence for the
      association between the CNTF gene and schizophrenia or personality traits in the
      Japanese population.

PMID- 16969279
TI  - No association of the C677T methylenetetrahydrofolate reductase polymorphism with
      schizophrenia.
AB  - Some serological and genetic studies have suggested that alterations in folate
      metabolism are associated with increased vulnerability to schizophrenia. In
      particular, these findings are most striking for the role of a putatively
      functional variant (C677T) in the methylenetetrahydrofolate reductase (MTHFR)
      gene. To test the hypothesis that the T allele and the TT genotype are risk
      factors for psychosis, we genotyped the C677T polymorphism in 206 participants
      with schizophrenia or schizoaffective disorder and 359 participants from a
      population control sample. Neither the T allele nor the TT genotype was
      associated with increased risk for schizophrenia. These results do not support a
      role for the C677T MTHFR variant in schizophrenia.

PMID- 16969280
TI  - Induction immunosuppression.
AB  - Induction immunosuppression is intense, prophylactic therapy used at the time of
      transplantation based on the empiric observation that more powerful
      immunosuppression is required to prevent acute rejection early. In the past
      decade, there has been a growing trend towards the use of specialized agents such
      as antibody therapies for induction. In general, these agents have been shown to
      reduce the rate of acute rejection. However, their use has not been clearly shown
      to improve long-term transplant outcomes. This overview will review the
      biological basis for induction immunosuppression and the mechanisms of action of
      those specialized induction agents currently in clinical use. Clinical trials
      investigating induction regimens will be evaluated, and an individualized
      approach to the use of induction immunosuppressants will be presented.

PMID- 16969281
TI  - Cardiovascular complications after renal transplantation and their prevention.
AB  - By the time of renal transplantation, end-stage renal disease patients have a
      huge burden of cardiovascular disease (CVD) and are heavily saturated with
      atherosclerotic risk factors. Worsening of preexisting risk factors or new CVD
      risk factors may develop in the posttransplant period consequent in part to the
      diabetogenic and atherogenic potential of immunosuppressive drugs. The annual
      risk of a fatal or non-fatal CVD event of 3.5 to 5% in kidney transplant
      recipients is 50-fold higher than the general population. Renal allograft
      dysfunction, proteinuria, anemia, moderate hyperhomocysteinemia and elevated
      serum C-reactive protein concentrations, each dependently confer greater risk of
      CVD morbidity and mortality in the posttransplant period. Long-term care of renal
      transplant recipients should programmatically incorporate the recommendations of
      the National Kidney Foundation Working Groups and European Best Practice
      Guidelines Expert Group on Renal Transplantations into the management of
      hypertension, dyslipidemia, smoking, and posttransplant diabetes mellitus. Timely
      utilization of coronary revascularization procedures should be undertaken as
      these treatments are equally effective in the kidney transplant population.

PMID- 16969282
TI  - Outcomes of renal transplantation for recipients with lupus nephritis: analysis
      of the Organ Procurement and Transplantation Network database.
AB  - Prior analyses of transplant outcomes in lupus transplant recipients have not
      consisted of multivariate analyses in the modern immunosuppressive era. Here, we
      compared patient and graft outcomes in lupus and non-lupus recipients
      transplanted between 1996 to 2000 using the United Network of Organ Sharing/Organ
      Procurement Transplant Network database. We evaluated the impact of recipient and
      donor demographic factors, time on dialysis and the initial immunosuppression
      regimen on rejection rates and transplant outcomes. Univariate analysis showed
      similar graft but better patient survival rates for primary lupus and non-lupus
      transplant recipients (5-year patient survival rates for lupus cohort 85.2% for
      deceased donor transplants and 92.1% for living donor transplants as opposed to
      82.1% and 89.8% respectively for the non-lupus cohort; P=0.05 and 0.03) but
      similar patient survival rates for deceased donor retransplant patients. After
      controlling for confounding factors, no differences in patient or graft survival
      were seen between the two groups. No difference in acute rejection rates were
      observed in deceased donor transplants, but there was a small but significant
      increase in the risk of acute rejection in living donor lupus transplant
      recipients (hazard ratio=1.19, P=0.05). Risk of graft failure was lower for
      deceased donor recipients receiving MMF (five-year graft loss rate=29.6% for MMF
      vs. 40.2% for those not receiving MMF, P<0.0001), but no differences were seen
      among living donor recipients. Outcomes were similar regardless of type of
      calcineurin inhibitor, induction therapy, and time on dialysis. We conclude that
      lupus transplant recipients have outcomes generally equivalent to non-lupus
      transplant recipients.

PMID- 16969283
TI  - Comparing survival after transplantation with survival on dialysis: net benefit
      or a way to identify healthier patients?

PMID- 16969284
TI  - Noninvasive assessment of early kidney allograft dysfunction by blood oxygen
      level-dependent magnetic resonance imaging.
AB  - BACKGROUND: Blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI)
      is a noninvasive method to assess tissue oxygen bioavailability, using
      deoxyhemoglobin as an endogenous contrast agent. We hypothesized that BOLD-MRI
      could accurately discriminate different types of rejection early after kidney
      transplantation. METHODS: Twenty-three patients underwent imaging in the first
      four months posttransplant. Five had normal functioning transplants and 18 had
      biopsy-proven acute allograft dysfunction (acute tubular necrosis [ATN, n=5] and
      acute rejection [n=13] including borderline rejection: n=3; IA rejection: n=4;
      IIA rejection: n=6: C4d(+) rejection: n=9). RESULTS: Mean medullary R2* (MR2*)
      levels (a measure directly proportional to tissue deoxyhemoglobin levels) were
      significantly higher in normal functioning allografts (R2*=24.3/s+/-2.3) versus
      acute rejection (R2*=16.6/s+/-2.1) and ATN (R2*=20.9/s+/-1.8) (P<0.05). The
      lowest MR2* levels were observed in acute rejection episodes with vascular injury
      i.e. IIA and C4d (+). Similarly, the lowest medullary to cortical R2* ratios
      (MCR2*) were present in allografts with IIA (1.24+/-0.05) and C4d(+) rejection
      (1.26+/-0.06). ROC curve analyses suggested that MR2* and MCR2* values could
      accurately discriminate acute rejection in the early posttransplant period.
      CONCLUSIONS: BOLD-MRI demonstrated significant changes in medullary oxygen
      bioavailability in allografts with biopsy-proven ATN and acute rejection,
      suggesting that there may be a role for this noninvasive tool to evaluate kidney
      function early after transplantation.

PMID- 16969285
TI  - Partial donor-specific tolerance to delayed skin grafts after rejection of
      hematopoietic cell graft.
AB  - BACKGROUND: Donor-specific tolerance (DST) is induced after allogeneic
      hematopoietic cell transplantation (HCT) and is a potential strategy for
      prolonging survival of solid organ grafts. DST may persist in recipients with
      transient mixed hematopoietic chimerism (MC) when solid organ transplantation and
      HCT are done concomitantly. METHODS: In a canine model of allogeneic HCT after
      nonmyeloablative conditioning, DST to skin grafts was evaluated in dog leukocyte
      antigen (DLA)-identical recipients with stable MC (n=11), or after rejection of
      the hematopoietic cell (HC) graft (n=19). RESULTS: There was significant
      improvement in the survival of DLA-identical HC donor-derived skin grafts in
      recipients with MC compared to normal recipients (n=7; P<0.0001). However, HC
      donor-derived skin grafts in four recipients with MC developed an inflammatory
      reaction without skin graft loss. This may represent partial DST. Survival of DLA
      identical HC donor-derived skin grafts was also significantly prolonged compared
      to normal recipients even when skin grafting was delayed until after rejection of
      the HC graft (P=0.002). An inflammatory reaction developed in all nine of the
      surviving HC donor-derived skin grafts in this group, but there was no graft loss
      at last follow-up (median, 30 [range, 9-84] weeks). An increased time to
      rejection of the hematopoietic graft was associated with prolonged survival of
      the subsequent skin graft (P=0.02). CONCLUSION: In a model of stable MC, DST to
      skin grafts may be complete or partial. Partial DST can persist after HC graft
      rejection even if solid organ transplantation is delayed. Further investigations
      are required to understand the mechanisms responsible for DST after allogeneic
      HCT.

PMID- 16969286
TI  - Risk factors and severe outcome in thrombotic microangiopathy after allogeneic
      hematopoietic stem cell transplantation.
AB  - BACKGROUND: Thrombotic microangiopathy (TMA) has been described as severe
      complication after hematopoietic stem cell transplantation (HSCT). The principal
      aim of this study was to focus the incidence and the outcome of TMA in the era of
      more complex HSCTs. METHODS: We analyzed the role of some predicting factors for
      the incidence and the outcome of TMA after HSCT. We enrolled 539 consecutive
      patients (307 males, median age 31 years) undergoing HSCT from match or mismatch
      human leukocyte antigen family donor (314) or match/mismatch unrelated (195) and
      haploidentical donor (30) for malignant or nonmalignant diseases. TMA diagnosis
      was performed by homogeneous clinical and laboratory criteria. RESULTS: Sixty
      four of 539 patients presented TMA (11,87%) and the five-year cumulative
      incidence of TMA was 14% (HR=0.13). Fifty nine of 64 patients were affected by
      malignant and 5/64 by non-malignant diseases. On multivariate analysis, TMA
      occurrence was influenced by graft versus host disease >grade II (P=0.0001),
      donor type (P=0.029), gender (P=0.0233), total body irradiation based
      conditioning regimen (P=0.0041). Three factors for TMA outcome proved to be
      statistically significant by multivariate analysis: age (P=0.009), donor type
      (P=0.0187) and TMA index (P=0.029). The TMA mortality rate was 50%. The outcome
      was influenced by defibrotide (P=0.02 in univariate analysis). CONCLUSIONS: The
      study underlines the possibility of finding out which patients are more prone to
      developing post-HSCT TMA, and identifies which risk factors are more frequently
      associated with a dismal outcome after TMA.

PMID- 16969287
TI  - Acute renal failure following kidney transplantation associated with
      myoglobinuria in patients treated with rapamycin.
AB  - BACKGROUND: Since using an immunosuppression regimen that includes rapamycin, we
      have occasionally encountered renal transplant patients who develop unexpected
      severe acute renal dysfunction. Biopsies obtained in these recipients demonstrate
      acute tubular necrosis (ATN) occasionally associated with tubular casts giving
      the classic appearance of myoglobin casts. METHODS: We retrospectively reviewed
      all biopsies from consecutively transplanted kidneys engrafted between April 9,
      2002 and June 29, 2004 to determine the incidence of ATN, ATN with intratubular
      casts, and casts with the classic myoglobin appearance. The clinical setting,
      treatment, and outcomes of those patients with classic myoglobin-appearing casts
      are reviewed. RESULTS: Histological ATN as the principal finding in at least one
      biopsy occurred in 10.5% (57/543) of patients. About half of these patients
      (30/57) had tubular casts present in at least one biopsy and in 14 of these the
      casts had a classic appearance of myoglobin casts. These myoglobin-appearing
      casts were only noted in patients receiving rapamycin. A review of 28 ATN
      biopsies from an earlier prerapamycin era did not demonstrate similar myoglobin
      appearing casts. Immunostaining for myoglobin was positive in all 14 recipient
      biopsies. This was confirmed by western blot analyses in three of five patient
      biopsies tested. Three of three recipients tested had elevated serum creatine
      phosphokinase levels and detectable serum myoglobin. All 14 patients slowly
      resolved their acute renal dysfunction and no grafts were lost. CONCLUSION: We
      conclude that myoglobinuria with myoglobin cast formation can occur following
      rapamycin administration, and may be a causative factor in the development of
      unexpected severe acute renal dysfunction.

PMID- 16969288
TI  - Optimizing living donor kidney graft function by donor-recipient pair selection.
AB  - BACKGROUND: With the rising prevalence of living donor kidney transplantations
      (LDKT), we increasingly encounter transplant candidates who present with multiple
      potential living donors. For a given candidate, it can be unclear which donor
      offers the best opportunity for optimal posttransplant graft function. This study
      was undertaken to determine the relative contributions of individual donor
      demographic factors on graft function following LDKT. METHODS: All LDKT donor
      recipient pairs between January 1, 1999 and December 31, 2002 entered into the
      Scientific Registry of Transplant Recipients (SRTR) were reviewed. Suboptimal one
      year graft function was defined as a serum creatinine (Cr) greater than 1.5
      mg/dL. RESULTS: Of 20,528 adult LDKTs performed, 8,603 donor-recipient pairs had
      complete donor, recipient, and one year graft function data. Over one third (36%)
      of all LDKTs had suboptimal one year graft function. Logistic regression
      identified simple recipient and donor characteristics associated with suboptimal
      one year graft function. Four recipient factors (age, gender, race, and size),
      three donor factors (age, gender, and size) and recipient-donor relatedness were
      used to derive an equation that predicts the risk of suboptimal one year graft
      function posed by each potential living donor for a given transplant candidate.
      CONCLUSIONS: In the setting of multiple potential living kidney donors, this
      quantitative tool may facilitate the choice of the optimal donor.

PMID- 16969290
TI  - Assessing relative risks of infection and rejection: a meta-analysis using an
      immune function assay.
AB  - BACKGROUND: Long-term use of immunosuppressants is associated with significant
      morbidity and mortality in transplant recipients. A simple whole blood assay that
      has U.S. Food and Drug Administration clearance directly assesses the net state
      of immune function of allograft recipients for better individualization of
      therapy. A meta-analysis of 504 solid organ transplant recipients (heart, kidney,
      kidney-pancreas, liver and small bowel) from 10 U.S. centers was performed using
      the Cylex ImmuKnow assay. METHODS: Blood samples were taken from recipients at
      various times posttransplant and compared with clinical course (stable,
      rejection, infection). In this analysis, 39 biopsy-proven cellular rejections and
      66 diagnosed infections occurred. Odds ratios of infection or rejection were
      calculated based on measured immune response values. RESULTS: A recipient with an
      immune response value of 25 ng/ml adenosine triphosphate (ATP) was 12 times (95%
      confidence of 4 to 36) more likely to develop an infection than a recipient with
      a stronger immune response. Similarly, a recipient with an immune response of 700
      ng/ml ATP was 30 times (95% confidence of 8 to 112) more likely to develop a
      cellular rejection than a recipient with a lower immune response value. Of note
      is the intersection of odds ratio curves for infection and rejection in the
      moderate immune response zone (280 ng/ml ATP). This intersection of risk curves
      provides an immunological target of immune function for solid organ recipients.
      CONCLUSION: These data show that the Cylex ImmuKnow assay has a high negative
      predictive value and provides a target immunological response zone for minimizing
      risk and managing patients to stability.

PMID- 16969289
TI  - Assessment of the risk of chronic allograft dysfunction after renal
      transplantation in a randomized cyclosporine withdrawal trial.
AB  - BACKGROUND: We report the two-year follow-up of a trial comparing the three-month
      postgraft discontinuation of either cyclosporine (CsA) or mycophenolate mofetil
      (MMF) from a triple-drug regimen after de novo renal transplantation. METHODS:
      One hundred and eight patients were enrolled in this study and randomized to be
      withdrawn from CsA (MMF group, n=54) or MMF (CsA group, n=54). RESULTS: Despite
      an increased risk of acute rejection and a lower, but nonsignificant, two-year
      graft survival, CsA withdrawal induced a sustained improvement of the renal
      function. At one year, the chronic allograft damage index was similar in both the
      MMF and CsA groups. However, CsA elimination resulted in a higher incidence of
      C4d deposits, irrespective of the occurrence of a prior acute rejection. While
      this finding could suggest a risk of chronic rejection in the MMF group, the
      outcome did not appear to be related to the C4d status. Moreover, logistic
      regression analysis showed that only two factors, acute rejection and the one
      year glomerular filtration rate level, were predictive of a significant decline
      of the renal function at two years. CONCLUSIONS: These results point out the need
      to secure the minimization of the calcineurin inhibitors after renal
      transplantation, in order to reduce the risk of acute rejection in these
      patients, because this strategy allows the improvement of the one-year renal
      function which is predictive of a chronic allograft dysfunction.

PMID- 16969291
TI  - Evaluating the survival benefit of kidney retransplantation.
AB  - BACKGROUND: The magnitude of the survival benefit associated with kidney
      retransplantation has not been well studied. METHODS: Using data from the
      Canadian Organ Replacement Register (CORR), we studied patients (n=3,067)
      initiating renal replacement therapy during 1981-1998 who had received a
      transplant and experienced graft failure (GF). Such patients were followed until
      death, loss to follow-up or the end of the observation period (December 31,
      1998). Using Cox regression, we estimated the post-GF covariate-adjusted hazard
      ratio (HR) for retransplant versus dialysis, and determined whether the contrast
      differed across patient subgroups. Through nonproportional hazards models, we
      also examine patterns in the retransplant/dialysis HR with time following
      retransplant. RESULTS: Overall, retransplantation is associated with a covariate
      adjusted 50% reduction in mortality, relative to remaining on dialysis (HR=0.50;
      P<0.0001). This benefit is most pronounced in the 18- to 59-year age group.
      Retransplanted patients were at significantly higher risk of death relative to
      patients on dialysis only during the first month posttransplant (HR=1.66;
      P=0.047), and experienced significantly reduced mortality thereafter.
      CONCLUSIONS: Following primary graft failure, retransplantation is associated
      with significantly reduced mortality rates among Canadian end-stage renal disease
      patients. Further study should be undertaken to assess the applicability of our
      findings to other patient populations.

PMID- 16969292
TI  - Cinacalcet chloride is efficient and safe in renal transplant recipients with
      posttransplant hyperparathyroidism.
AB  - BACKGROUND: Persistent hyperparathyroidism (HPT) is observed in approximately 50%
      of kidney transplant recipients one year after transplantation. It may result in
      hypercalcemia, hypophosphatemia, bone demineralization, vascular calcification,
      lithiasis, and participate in chronic allograft nephropathy. We evaluated the use
      of the calcimimetic cinacalcet chloride to correct chronic hypercalcemia in
      posttransplant HPT, in a prospective single-center study. METHODS: Nine patients
      with persistent hypercalcemia (>2.6 mmol/L) and stable graft function were
      treated with cinacalcet (30 mg/day, thereafter adapted to obtain normal serum Ca
      levels) for six months. Their immunosuppressive schedule included mycophenolate
      mofetil (MMF), steroids, and cyclosporine A (4), tacrolimus (4), or sirolimus
      (2). RESULTS: Serum Ca levels significantly decreased from 2.75+/-0.15 to 2.59+/
      0.10, 2.42+/-0.29 and 2.44+/-0.25 mmol/L by one, two, and six months,
      respectively (P<0.02, Wilcoxon test for paired data, for all the data points).
      Parathyroid hormone (PTH) serum levels decreased from 171+/-102 to 134+/-63 pg/ml
      by two months (P<0.05) and stabilized thereafter (148+/-99 pg/ml at six months;
      NS). No changes in glomerular filtration rate (49.8+/-18.6 and 51.3+/-19 ml/min
      at initiation and six months, respectively) and no variation in serum
      concentration of the immunosuppressive drugs were observed. Three patients
      withdrew the treatment because gastrointestinal intolerance. CONCLUSION:
      Cinacalcet allows the correction of hypercalcemia with no interference in
      immunosuppressive treatment or renal function. However, whether the increased
      intolerance observed was due to the association of cinacalcet chloride with other
      drugs required in renal transplantation (e.g., MMF) needs to be assessed.

PMID- 16969293
TI  - Potential of an injectable polymer to prevent hyperacute rejection of ex vivo
      perfused porcine lungs.
AB  - BACKGROUND: Removal of xenoreactive antibodies in pig-to-human lung
      transplantation by columns or organ perfusions proofed to be unsatisfactory and
      associated with adverse effects. In an ex-vivo lung perfusion model, we evaluated
      the potential of a soluble trisaccharide polymer (GAS914) to bind alpha-Gal
      antibodies and to protect a pulmonary xenograft from hyperacute rejection (HAR)
      and pulmonary xenograft dysfunction. METHODS: Porcine lungs were perfused with
      fresh human blood for 240 min. In the GAS914 treated group (n=6) the polymer was
      applied in three different concentrations. The control group (n=6) received no
      GAS914. Survival and function of perfused xenografts were monitored, and alpha
      Gal antibodies as well as cytolytic anti-porcine antibodies analyzed. RESULTS: In
      the GAS-treated group survival of lungs was significantly prolonged, pulmonary
      vascular resistance reduced, pulmonary edema prevented, and oxygenation improved.
      On histopathological evaluation application of GAS resulted in minimal graft
      injury and significantly less deposition of the terminal complement complex C5b
      9. Following application of GAS914, up to 89.8% of IgG alpha-Gal, 79.5% of IgM
      and 73.6% of anti-porcine antibodies in the human blood were bound by the
      polymer. Subsequent perfusion of porcine lungs resulted in absorption of only 3%
      of the baseline IgG alpha-Gal antibodies in the GAS914 group, compared to 87% in
      the controls. CONCLUSIONS: In this ex-vivo lung perfusion model, a trisaccharide
      polymer prevented immediate HAR, due to effective removal of alpha-Gal
      antibodies. In combination with additional strategies GAS914 may be a valuable
      tool in overcoming HAR and dysfunction of pulmonary xenografts.

PMID- 16969294
TI  - Critical roles of memory T cells and antidonor immunoglobulin in rejection of
      allogeneic bone marrow cells in sensitized recipient mice.
AB  - BACKGROUND: Allosensitization is a major risk factor for graft failure in
      clinical bone marrow transplantation, even with an human leukocyte antigen (HLA)
      matched combination under radiation-based conditioning regimens. The critical
      components of immunological memory in donor bone marrow graft rejection in
      allosensitized hosts remain unclear at present. METHODS: C57BL/6-recipient mice,
      which had been intraperitoneally injected with splenocytes from donor C3H mice on
      day -35 (sensitized recipients), had been lethally irradiated with 10-Gy whole
      body irradiation and were intravenously injected with T-cell-depleted bone marrow
      cells (TCD-BMC) from C3H mice or third-party SJL mice. RESULTS: Lethally
      irradiated recipient mice, which had been sensitized by donor splenocytes 5 weeks
      before the transplantation of TCD-BMC, completely rejected the donor-BMC in a
      donor-specific manner, whereas none of the nonsensitized recipient mice, all of
      which showed full allogeneic chimerism, rejected the donor TCD-BMC. Antibody
      mediated T cell and/or Natural Killer (NK) cell depletion did not improve the
      ability of the sensitized recipients to overcome the rejection even when a
      megadose of TCD-BMC was administered to the sensitized recipients. Furthermore,
      BMC rejection occurred in sensitized B cell-deficient mice. In adoptive transfer
      experiments, naive mice, which received a transfer of purified T cells from
      sensitized mice, rejected the donor BMC, but not those from nonsensitized mice.
      Moreover, naive mice, which received a transfer of serum containing antidonor
      immunoglobulin, rejected the donor BMC. CONCLUSIONS: These findings suggest that
      alloreactive memory T cells and antidonor immunoglobulin independently function
      to reject donor BMC in sensitized recipients.

PMID- 16969295
TI  - Differentially expressed genes in postperfusion biopsies predict early graft
      dysfunction after liver transplantation.
AB  - BACKGROUND: Preservation induced injury is a major contributing factor to early
      graft dysfunction in liver allograft recipients. We hypothesized that changes in
      gene expression represent the earliest indicator of ischemia/reperfusion-related
      injuries measurable in the graft and could be used as prognostic marker for the
      occurrence of graft-related complications. METHODS: We studied the expression of
      67 genes, known to play a role in acute inflammatory processes by real-time
      polymerase chain reaction in 59 postperfusion biopsies. The level of expression
      was correlated with the occurrence of graft-related complications. RESULTS: We
      identified six genes that were significantly correlated with the occurrence of
      early graft dysfunction (Spearman test, two-tailed; P<0.05). High C-reactive
      protein (CRP) gene expression levels correlated significantly with the need of
      therapeutic interventions due to graft-related complications (P=0,011).
      Furthermore, five genes related to vascular endothelial cell physiology (CTGF,
      WWP2, CD274, VEGF. and its receptor FLT1) showed significantly reduced expression
      in the postperfusion biopsies of patients with need of therapeutic interventions
      due to graft-related complications in the first month (P<0.05). Using a risk
      score based on the expression of these five genes, complications could be
      predicted with 96% sensitivity (ROC analysis, specificity: 74%, positive
      predictive value: 72%, negative predictive value: 96%). CONCLUSION: Quantitative
      gene expression analysis in postperfusion biopsies may be a valuable tool to
      prospectively identify patients at risk for early clinical allograft dysfunction
      after liver transplantation.

PMID- 16969296
TI  - Multidrug resistance gene-1 (MDR-1) haplotypes have a minor influence on
      tacrolimus dose requirements.
AB  - P-glycoprotein (P-gp) and the drug metabolizing enzymes have major
      pharmacokinetic effects. Variability in tacrolimus absorption is influenced by P
      gp activity which, in turn, is affected by single nucleotide polymorphisms (SNPs)
      within the multidrug resistance-1 gene (MDR-1). Tacrolimus dose requirements of
      206 stable renal transplant patients were related to MDR-1 genotypes of SNPs
      C1236T, G2677T/A and C3435T, as well as haplotypes: C-G-C and T-T-T. Lower dose
      normalized blood tacrolimus concentrations were achieved for: 2677-GG genotype
      patients, as compared to 2677-TT, and for 3435-CC patients as compared to 3435-TT
      patients. There was a small, but significant, difference in dose requirements
      between haplotypes C-G-C and T-T-T patients, which was not significant when
      patients were subclassified as producers and non-producers of cytochrome P450 3A5
      (CYP3A5). The activities of CYP3A5 and P-gp have been shown to influence
      bioavailability of several drugs. Our data suggest that MDR-1 haplotypes have a
      relatively minor association with tacrolimus pharmacokinetics.

PMID- 16969298
TI  - A new mouse model for intraportal islet transplantation with limited hepatic lobe
      as a graft site.
AB  - Intraportal site is the standard for grafting in clinical islet transplantation.
      In the mouse model, the whole liver has been used as the grafting site to mimic
      clinical islet transplantation. However, this model lacks the potency to directly
      assess the contribution of the islet graft to diabetes control. Only
      demonstrating the immediate recurrence of diabetes in a surviving recipient after
      the removal of the islet graft can validate this assessment. In this study, we
      develop a mouse model of intraportal islet transplantation equipped with the
      potency of this assessment by injecting islets selectively into the right hepatic
      lobe under temporal clamp of the left portal vein. The mouse of this model
      survives after the right hepatectomy by which the islet graft is removed. This
      model can be applied to investigate both the specific graft-recipient interaction
      in the liver and the islet graft contribution to the control of diabetes.

PMID- 16969297
TI  - Serum KL-6 as a marker for bronchiolitis obliterans syndrome after lung
      transplantation.
AB  - Bronchiolitis obliterans (BO) is the pathologic manifestation of chronic
      allograft rejection in lung transplant recipients and specific diagnosis requires
      invasive tests. BO causes progressive obstruction of the small airways. The term
      bronchiolitis obliterans syndrome (BOS) is a clinical surrogate for the
      histopathologic diagnosis of BO and is measured by lung function testing. KL-6 is
      a glycoprotein expressed on pulmonary epithelial cells and it is present in the
      serum of normal individuals in small amounts. Serum KL-6 has been shown to be a
      useful marker of disease activity in interstitial lung diseases. We demonstrated
      that serum levels of KL-6 are elevated in lung transplant recipients with BOS
      when compared with those without BOS and healthy controls. Our results indicate
      that serum KL-6 measurement has the potential to serve as a noninvasive
      diagnostic test for the detection of BO in lung transplant recipients.

PMID- 16969299
TI  - Successful transplantation of donation-after-cardiac-death liver in recipient
      with MELD score of 40.

PMID- 16969300
TI  - Successful endovascular treatment of a leaking pseudoaneurysm without graft loss
      after simultaneous pancreas and kidney transplantation.

PMID- 16969301
TI  - Liver transplantation for double primary hepatic cancer-hepatocellular carcinoma
      and intrahepatic cholangiocarcinoma.

PMID- 16969302
TI  - Splenectomy and preoperative risks in ABO-incompatible kidney transplants.

PMID- 16969303
TI  - ABO-incompatible kidney transplantation with and without splenectomy.

PMID- 16969304
TI  - [Improving health care safety].

PMID- 16969305
TI  - [Ringworm relapse: school suspension is not necessary].

PMID- 16969306
TI  - [Urinary tract infections in women].

PMID- 16969307
TI  - [Making it easier for public health physicians to improve health policies].

PMID- 16969308
TI  - [Tinnitus and cognitive-behavioral therapy: results after 1 year].
AB  - INTRODUCTION: Tinnitus is a common auditory symptom that interferes with
      activities of daily living and is often associated with anxiety and depression.
      METHOD: This study included consecutive patients with chronic intense tinnitus
      for more than six months who were treated with Tinnitus Retraining Therapy (TRT),
      a cognitive-behavioral therapy, after previous treatment failed and after a
      clinical evaluation based on standardized questionnaires, including the Tinnitus
      Handicap Questionnaire (THQ). One year after the end of the TRT, the treatment
      was evaluated by the same standardized questionnaires. RESULTS: This prospective
      study included 96 consecutive patients (49 women, 47 men, mean age: 48 years).
      Tinnitus improved significantly in 75%, where significant improvement was defined
      as a final THQ score of less than 500 after CBT. This improvement varied
      according to initial THQ scores and was seen in: all patients with moderate
      (THQ<500), 70.3% of the patients with intermediate (500<THQ>1001), and 34.8% of
      patients with severe (THQ>1000) tinnitus. CONCLUSION: CBT shows promise as a
      treatment of tinnitus-related distress.

PMID- 16969309
TI  - [Morbidity/mortality reviews: assessment of their implementation in one
      hospital].
AB  - OBJECTIVES: The objective of this study was to describe the steps involved in
      establishing a morbidity/mortality review committee (MMRC) to analyze the causes
      of avoidable deaths or life-threatening complications and the development of
      plans and protocols to avoid their recurrence. METHODS: The MMRC included
      physicians from each hospital department. Each member was responsible for
      organizing departmental meetings to analyze its avoidable deaths and life
      threatening complications. RESULTS: During its meetings three times a year, the
      MMRC developed a method for analysis of these serious events. Each department
      organized 3 (range: 1-12) meetings a year and analyzed 1-3 cases at each. Over 30
      months, 35,817 patients were admitted to the hospital and 341 (1%) died. The
      unexpected mortality rate varied by department and specialty (median: 27%, range:
      6-65%). In all, 92 cases were referred to MMRC meetings (27%; range: 6-70% of
      hospital deaths), and 30% of them involvement nosocomial diseases. Heart disease
      was the primary cause of unexpected deaths. DISCUSSION: The principal
      improvements involved medical and surgical strategies, surgical techniques, drug
      prescriptions, and patient monitoring.

PMID- 16969310
TI  - [Epidemiology of tinea capitis. Five-year retrospective study in three hospitals
      in the Val de Marne].
AB  - OBJECTIVE: Describe the epidemiology of Tinea capitis in three hospitals in the
      Val de Marne (suburban district southeast of Paris) and evaluate the usefulness
      of screening the families of index cases. METHODS: The study included 3
      hospitals: Henri Mondor Hospital, Creteil Intermunicipal Hospital Center and
      Bicetre Hospital. Index patients had a positive culture for dermatophytes during
      visits to the mycology-dermatology or pediatric clinics from January 1998 through
      December 2002. The diagnostic procedure was identical in all centers. In two
      centers, scalp samples were taken routinely from family members, even in the
      absence of clinical lesions. Species were identified according to the phenotypic
      features of the cultures. We recorded the age, sex, and geographic origin of each
      patient, when available. RESULTS: Samples were obtained from 487 outpatients
      (including family members): 383 were positive (356 children under 16 years, 27
      adults). Of the children with positive cultures, 214 were boys (60%); of the
      adults, 18 (66%) were women. Distribution of geographic origin was: sub-Saharan
      Africa (71%), Europe (10%), Caribbean (5%) and North Africa (4,7%). Species
      identification confirmed the predominance of anthropophilic species, with 46% of
      the isolates Trichophyton soudanense and 33% Microsporum langeronii. T. violaceum
      was reported in 5.5% of cases and T. tonsurans in 2.8%. M. canis (9%), found in
      34 Europeans, was the main zoophilic species. Family screening accounted for 263
      of the 487 outpatients. Of 242 children from 86 families, 153 (63%) had positive
      cultures. Of the 21 parents, 5 had a positive culture. Globally, the family
      screening identified 158 cases in 263 tests (60%). CONCLUSION: Tinea capitis in
      the Val de Marne is mainly due to anthropophilic species and involves children of
      African origin. The frequency of family contamination indicates that routine
      screening of family members of infected children is valuable.

PMID- 16969311
TI  - [Management of urinary tract infections in women. Epidemiologic survey of 7916
      women in general practice].
AB  - OBJECTIVE: To evaluate the management of urinary tract infections in women by
      general practitioners and compare it with official French guidelines. METHODS:
      This survey enrolled 1587 general practitioners in France and 7916 adult women.
      Exclusion criteria for patients included: pregnancy, diabetes, neurogenic
      bladder, or urinary catheters. During the visit at which the diagnosis was made,
      physicians completed a questionnaire that included diagnostic and management
      details, in particular, prescription of further examinations. RESULTS: According
      to the French guidelines, 37% of women had an upper or complicated urinary tract
      infection, although one third of the complicated infections were so defined only
      by the patient's age (>65 years). Additional testing was prescribed for 36% of
      the women with acute uncomplicated cystitis. CONCLUSION: This study shows that
      the management of urinary tract infections in women does not comply with current
      guidelines, especially in cases of acute uncomplicated cystitis. The use of age
      alone as a complicating factor should be reconsidered.

PMID- 16969312
TI  - [Adherence intervention for HIV-infected patients receiving antiretroviral
      treatment. Implementation and initial assessment].
AB  - OBJECTIVE: To describe the implementation and initial results of a specific
      educational and counseling intervention to examine and improve adherence to
      antiretroviral therapy (ARV) in HIV-infected patients. METHOD: Four patient
      profiles were defined: 1) discontinuation and 2) failure: patients with
      virological failure (defined as two consecutive viral loads>200 copies/mL) at ARV
      discontinuation or under treatment, both seen after the fact; 3) preparation:
      naive patients seen before starting treatment, and 4) reinforcement: patients in
      treatment seen for counseling to prevent virological failure. A clinical
      psychologist, nurse and hospital pharmacist jointly conducted the session. Data
      collected include standardized information about the characteristics of HIV
      infection and ARV regimens, and demographic, behavioral, social and cultural
      indicators. CD4 cell counts and HIV viral loads were recorded at D0, M1, M3, M9
      and M12. The effectiveness of the adherence intervention was defined separately
      for each patient profile based on some combination of taking or restarting an ARV
      regimen, virological response, and M12 follow-up. RESULTS: The study included 139
      patients between November 1998 and April 2000. The intervention was defined as
      effective in 50% and 40% of the discontinuation (n=26) and failure (n=61)
      patients respectively, 84% of those with preparation profile (n=37) and 93%
      (14/15) of reinforcement patients. Only undetectable HIV viral load at M3 was
      significantly associated with the effectiveness of the adherence intervention for
      all 4 profiles. The preventive interventions (preparation and reinforcement) were
      less effective in patients from outside Europe (p=0.013). CONCLUSION: The
      adherence intervention was more effective in preventing virological failure than
      in restoring ARV effectiveness among patients who had already experienced
      virological failure. It should therefore be proposed primarily before starting
      ARV, to prevent failure in treatment-naive patients, especially those from
      outside Europe.

PMID- 16969313
TI  - [Hepatitis C in prison settings: screening and therapy are improving. Comparative
      survey between 2000 and 2003].
AB  - OBJECTIVE: To determine the real frequency of hepatitis C (HCV) in French
      prisons. AIMS AND METHODS: To evaluate the changes in HCV screening and
      therapeutic practices in prisons between 2000 and 2003 by comparing results of
      mail surveys of prison medical units both years (* if p<0.01). RESULTS: 88 units
      (51%) responded to both surveys. In 2003, HCV serologic screening was routinely
      performed in 28% (36%* in 2000) of prisons and routinely offered in 66% (35%*).
      Mean HCV prevalence was 6.9% in 2003 and 6.7% in 2003. There were 534 liver
      biopsies in 2003 and 545 in 2003, that is, an average of 6 biopsies per unit per
      year both years. Treatment was provided to 297 patients in 2003 and 164 in 2000,
      but 29% of prisons offered no treatment in 2003, and 44% (*) in 2000. Overall 14%
      of HCV-infected prisoners received therapy. CONCLUSION: The prisons participating
      in this study and the inmates they include were representative of the French
      prison population. HCV prevalence in French prisons appears stable. Routinely
      suggested or conducted screening is widespread. The number of liver biopsies is
      stable but low, and the number of patients receiving treatment has increased
      significantly.

PMID- 16969314
TI  - [Bilateral retinal detachments. Risk factors and treatment efficacy: 11 cases].
AB  - PURPOSE: The purpose of our study was to evaluate the incidence of bilateral
      retinal detachments and to analyze the risk factors for it and the anatomic and
      functional results of treatment. METHODS: Retinal detachment can be discovered in
      both eyes during an initial consultation. In other cases, retinal detachment may
      be seen in the second eye during follow-up of the first eye. RESULTS: Bilateral
      retinal detachments account for 11.7% of the retinal detachments in our hospital.
      Many factors are involved in bilateral detachment, including myopia and
      degenerative lesions. Treatment depends on the type of detachment. CONCLUSION:
      Treatment of bilateral detachments is difficult and depends on the specific type
      of detachment. Relatively young men are most at risk for bilateral detachments.

PMID- 16969315
TI  - [Churg-Strauss syndrome and pulmonary fibrosis: an unusual association].
AB  - INTRODUCTION: Churg-Strauss syndrome (CSS) is characterized by asthma,
      hypereosinophilia, and vasculitis involving at least two extrapulmonary organs.
      CASE: We report a case of a patient with antineutrophilic cytoplasmic antibody
      negative CSS who developed pulmonary interstitial fibrosis (PIF). DISCUSSION: The
      possible relations between CSS and PIF are discussed. Because this case report is
      the first to describe features of pulmonary fibrosis in a patient with CSS, we
      cannot know whether this association is causal or fortuitous.

PMID- 16969316
TI  - [Hypothalamic-pituitary Langerhans cell histiocytosis in adults].
AB  - INTRODUCTION: Langerhans cell histiocytosis is a rare entity. Involvement of the
      pituitary region is frequently delayed and rarely studied. CASES: We report some
      clinical and paraclinical particularities of the disease in four women. Diabetes
      insipidus was the initial symptom in all cases, accompanied by panhypopituitarism
      at initial presentation in one woman. Hypopituitarism was diagnosed from 6 months
      to 4 years after the diabetes insipidus in the other cases, and systemic lesions
      appeared 3 to 6 years thereafter. Magnetic resonance imaging of the hypothalamic
      pituitary axis found tumors in two patients and infundibular thickening in the
      other two. One patient also had a partially empty sella. DISCUSSION: In adults,
      pituitary involvement seems to occur predominantly in women, and
      panhypopituitarism is possible at initial presentation. The clinical polymorphism
      of Langerhans cell histiocytosis makes this disease difficult and often slow to
      diagnose.

PMID- 16969317
TI  - [Fortuitous discovery of hydatid cyst of the breast].
AB  - INTRODUCTION: Hydatid cyst of the breast is rare even in areas of endemic
      echinococcosis. It accounts for 0.3% of all localizations and 2% of the uncommon
      sites. It can be isolated or associated with other localizations. CASE: We report
      the case of a hydatid breast cyst, associated with a pulmonary hydatid cyst,
      fortunately diagnosed by mammography and ultrasonography. Both cysts were
      removed. DISCUSSION: Hydatid breast cysts must be considered in any cystic breast
      mass, particularly in endemic countries.

PMID- 16969318
TI  - [Achilles tendon rupture during ofloxacin treatment and a short course of
      prednisolone].

PMID- 16969319
TI  - [Misleading paradiaphyseal calcifications: calcific tendonitis].

PMID- 16969320
TI  - [Colorectal cancer prognosis: some aspects].

PMID- 16969321
TI  - [Serotonin uptake inhibitors in young subjects: risk or opportunity?].

PMID- 16969322
TI  - [A cure for multiple myeloma?].

PMID- 16969323
TI  - [Preventing Alzheimer's disease: hopes and disappointments].

PMID- 16969324
TI  - [Efficacy of selective serotonin reuptake inhibitor treatment in children and
      adolescents].
AB  - Selective serotonin reuptake inhibitors (SSRIs) have been used increasingly since
      the early 1990s to treat anxiety disorders and depression in children and
      adolescents. Several recent reports, however, cast doubt on their efficacy and
      especially raise questions about their role in serious adverse effects (increase
      in suicidal ideation and suicide attempts as well as reactions involving
      irritability, hostility, self-harm and self-destructive actions). The efficacy of
      SSRIs (fluoxetine, sertraline, fluvoxamine, paroxetine) in the treatment of
      obsessive-compulsive disorders in this population is clear today, although their
      effects are globally relatively modest. SSRIs remain notably less effective than
      clomipramine for this indication, although a variety of factors (age, family
      history, and psychiatric comorbidity) are also likely to influence response to
      treatment. Only several placebo-controlled studies suggest that the SSRIs
      (fluoxetine, sertraline and fluvoxamine) may have some utility in the treatment
      of anxiety disorders (generalized anxiety, separation anxiety, social phobias) in
      children and teens. The additional benefits from SSRIs for this indication
      nonetheless require confirmation. Imipramine and related tricyclic
      antidepressants are ineffective in the treatment of depressive disorders in
      children and adolescents. Among the SSRIs, only fluoxetine has proven its
      efficacy for this indication, although its effect here too appears relatively
      modest. The efficacy of sertraline and paroxetine cannot be considered more than
      probable, requiring confirmation, and that of citalopram has not been
      demonstrated. Moreover, because of the risk of suicidal behavior observed in some
      studies, SSRIs are inadvisable for the treatment of depressive disorders in this
      population. Overall, although the currently available data show SSRIs to be
      moderately effective and useful in treating anxiety disorders and depression in
      children and adolescents, future studies must focus on more precise
      identification of their indications, especially relative to psychotherapeutic
      strategies, which are still considered to be the first-line treatment in these
      disorders. From a legal point of view, only sertraline has been authorized in
      France for the treatment of obsessive-compulsive disorders in this population.

PMID- 16969325
TI  - [New drugs for myeloma].
AB  - Thalidomide, administered orally, bortezomib (Velcade) intravenously and
      lenalidomide (Revlimid), also orally, are three agents that act on myeloma
      relapse. Thalidomide acts by a variety of mechanisms and is toxic to the
      peripheral nervous system as well as teratogenic. It acts in synergy with
      dexamethasone. Recent results prove that its use as first-line treatment combined
      with oral conventional "MP" chemotherapy improves survival in patients older than
      65 years. Its use as first-line treatment with this chemotherapy appears likely.
      Bortezomib is the first drug in the proteasome inhibitor class. It too is toxic
      to the peripheral nervous system and synergistic with dexamethasone. Several
      studies show its efficacy as first-line 'induction treatment' with dexamethasone,
      in patients to receive a subsequent autologous stem cell transplantation. The
      combination of bortezomib and "MP" is also promising. Lenalidomide, a structural
      analog of thalidomide, is effective in relapsing patients. Its toxicity is
      essentially hematologic. It is also synergistic with dexamethasone and promising
      as first-line treatment. These different drugs can be used successively at
      relapse, making myeloma a chronic disease. They can also be used together for
      greater effectiveness. These combinations will replace conventional
      chemotherapies in the future.

PMID- 16969326
TI  - [Risk factors for Alzheimer: towards prevention?].
AB  - Recent longitudinal studies have highlighted associations between Alzheimer's
      disease (AD) and several factors, especially some cardiovascular risk factors,
      including hypertension, diabetes, diet, obesity, and elevated levels of
      homocysteine and lipids in the blood. The strongest associations are with
      hypertension and diabetes. Moderate alcohol consumption also appears to be
      associated with a decreased risk of incident AD. Studies of the effect of
      interventions to control these risk factors on the onset and course of dementia
      report encouraging results about antihypertensive agents and statins. Benefits
      from other drug therapies such as nonsteroidal antiinflammatory drugs and
      antioxidants remain uncertain, and initial hopes for hormonal replacement therapy
      for postmenopausal women have not been confirmed. Physical, cognitive and leisure
      activities seem to provide protection against incident AD. Cautious
      interpretation is necessary in view of the possible biases in these studies
      (confounding factors as well as survival, regression dilution, and indication
      biases). These epidemiologic data raise questions about the diagnostic boundaries
      between AD and vascular dementia. Additional studies are needed to validate these
      concepts and to confirm the possible benefits of preventive measures.

PMID- 16969327
TI  - [Noninvasive assessment of liver fibrosis in patients with chronic hepatitis
      virus C].
AB  - Development of liver fibrosis, which leads to cirrhosis, is the principal
      complication of all chronic liver diseases, regardless of their cause. Knowledge
      of the existence and severity of fibrosis is important from diagnostic and
      prognostic viewpoints. Its assessment plays an essential role in the treatment
      decision and makes it possible to assess the risk of progression to cirrhosis and
      the onset of its complications. Histologic examination of the liver remains the
      reference examination for assessing the extent of fibrosis during chronic liver
      disease. Nonetheless, the number of patients needing assessment, the risks of the
      punch-biopsy and the cost of this invasive examination have led many to propose
      other tools to assess fibrosis. Some standard indicators (transaminases,
      platelets, prothrombin time) have long been recognized as indirect markers of
      extensive fibrosis. More recently, progress in our knowledge of the mechanisms of
      liver fibrogenesis have made it possible to identify different peripheral blood
      components that may be of clinical interest. Thus serum assays of elements of the
      extracellular matrix, their decay products, or enzymes involved in their
      metabolism have been proposed as noninvasive indicators. Among these, hyaluronic
      acid appears the most interesting. For several years, scores have been calculated
      with algorithms that combine several indicators determined simultaneously to
      assess fibrosis in patients with hepatitis C and sometimes other chronic liver
      diseases. The Fibrotest is the best validated and most widely used of these.
      Finally, Fibroscan is a device for the diagnosis and quantification of hepatic
      fibrosis, based on the technique of transient elastography. The relative roles of
      these noninvasive markers and the value of their combinations must still be
      determined.

PMID- 16969328
TI  - [Functional cellular imaging: revolution for oncology].

PMID- 16969329
TI  - [Basics of PET and PET/CT imaging: instrumentation and radiopharmaceuticals for
      clinical diagnosis].
AB  - Positron emission tomography (PET), like scintigraphy, is a type of functional
      and molecular imaging. Image resolution is better than with scintigraphy, and
      tomographic slices are obtained, as with CT and MRI. Modern PET machines are
      coupled with CT (PET/CT) and yield fused images that combine metabolic and
      anatomic approaches. Fludeoxyglucose (FDG), a radiolabeled glucose analog, is the
      most widely used radiopharmaceutical for clinical PET, but several other
      molecules are proposed for routine use. Clinical trials will determine which are
      of clinical interest. FDG imaging necessarily involves PET but clinical PET is
      not only FDG imaging.

PMID- 16969330
TI  - [FDG PET and its impact on patient's management in oncology].
AB  - FDG, a radioactive glucose analog for PET imaging, requires some precautions: it
      should be used only in patients with glycemia < 7mmol/L, fasting for at least 6 h
      but well hydrated, and after pregnancy is ruled out. FDG-PET has many indications
      in oncology. Its clinical utility has been documented in some circumstances,
      listed as routine indications in the European Principal Characteristics Summary
      and the French Standards, Options, and Recommendations. The European "Points to
      Consider" define as a principal criterion of clinical utility the impact of the
      imaging results on patient management. The original results presented here
      evaluate the clinical impact of FDG-PET among patients at Tenon Hospital by the
      rate of modifications in patient' management, determined with the same
      questionnaire as that used in two California studies of 2044 patients. Our
      response rate was lower than in our previous retrospective study in 2000 (34%
      versus 73%), probably because a prospective evaluation requires more work by the
      referring physician (who had to respond to two separate letters). On the other
      hand, the modification rate rose significantly (54% versus 46%, p<0.001),
      especially for colorectal cancer (58% versus 44%, p<0.02). The California studies
      had similar response rates (31%-48%, depending on the indication). Their
      modification rates were also similar, although higher for lymphoma (68%),
      colorectal (65%) and breast (58%) cancers.

PMID- 16969331
TI  - [PET and malignant cerebral tumors].
AB  - Normal biodistribution of FDG includes intense physiologic uptake in the brain,
      which consumes glucose. The high background therefore makes it difficult to
      detect the foci taking up glucose, which correspond to malignant lesions. FDG PET
      is nevertheless clinically useful for detecting high-grade gliomas, cerebral
      lymphomas and, in some cases, unexpected brain metastases in whole-body PET
      examinations. As an adjunct to CT and MRI, FDG-PET can make stereotactic
      radiosurgery more precise in targeting primary or secondary brain cancers and can
      differentiate necrotic fibrosis from viable cancer tissue during follow-up in
      cases of abnormal or equivocal MRI results. When available, methionine-(11C) PET
      delineates low grade gliomas accurately. Several fluorine (18F)-labeled
      radiopharmaceuticals have been proposed in this setting, with FET and FDOPA
      apparently the most effective. Four original clinical cases illustrating
      performances of FET and FDOPA PET in this setting are presented.

PMID- 16969332
TI  - [PET in head and neck cancers].
AB  - FDG PET is useful when cancer in the head or neck (except for tumors of the
      salivary glands, which cannot be characterized accurately) is diagnosed or
      suspected but not confirmed by biopsy. It can, for example, find evidence of
      suspicious lymph nodes in clinically N0 necks, detect foci suggestive of distant
      metastases or second cancers, and provide useful prognostic information. Because
      it can be very difficult to identify anatomical structures and landmarks on PET
      images in the head and neck region, PET/CT fusion is very helpful in this area.
      In early assessment of chemotherapy, the absence of a significant reduction in
      FDG uptake after one or two cycles predicts lack of efficacy and thus indicates
      the need to modify the regimen. Conversely, the disappearance of FDG foci
      indicates effective treatment and good prognosis but cannot rule out the
      persistence of any malignant tissue at the end of treatment, especially
      neoadjuvant. Diagnostic impact is probably greatest in monitoring for recurrence
      and restaging known recurrence: FDG PET should be performed - perhaps routinely -
      early enough that curative options are still open, but long enough after the end
      of treatment to avoid false positive results from inflammation. The strategy and
      timing of FDG PET during follow-up should be determined in more detail in the
      future, as should the role (if any) of fluorotyrosine (FET) PET in squamous cell
      carcinoma.

PMID- 16969333
TI  - [FDG-PET in localization of cancers of unknown primary origin].
AB  - FDG-PET can be successful in localizing the primary cancer when a metastasis is
      discovered but no primary tumor can be identified (cancer of unknown primary, or
      CUP) by physical examination, laboratory testing (for tumor markers, for example)
      or conventional imaging. The greatest number of PET studies in CUP concern
      secondary lesions in cervical lymph nodes, and PET is an established clinical use
      (highest ranking, 1A) according to the 3rd German Consensus Conference and an
      "option" in the French Standards, Options, and Recommendations. Success rates
      range from 30% to 50% in most studies using PET; a higher rate was reported
      recently with PET/CT. FDG-PET should be performed sufficiently early in cases of
      neurological paraneoplastic syndrome, because established lesions become
      irreversible. Identification of the antibody present helps to specify the organ
      and FDG-PET can then localize the lesion; together these techniques make it
      possible to perform curative surgery even when the primary tumor is not visible.
      The success rate is somewhat lower than in cases of metastasis, around 35%. The
      clinical utility of PET in other paraneoplastic syndromes has not yet been
      sufficiently studied, but these conditions are rare. It is precisely in cases
      with a kind of 'orphan' indication that FDG PET should be considered, as an
      effective "problem solver".

PMID- 16969334
TI  - [PET in thyroid cancers].
AB  - FDG PET can detect thyroid cancer in patients referred for exploration of a
      different cancer. Because of its lack of specificity, however, this modality is
      not indicated for examination of thyroid nodules: ultrasonography and fine needle
      biopsy with cytology allow histological diagnosis, which can be completed by
      iodine-123 scintigraphy when an autonomous nodule is suspected. No information is
      currently available about the utility of FDG PET in preoperative staging. In
      follow-up of patients undergoing thyroidectomy for adenocarcinoma, FDG PET is
      useful for detecting recurrence in cases where serum thyroglobulin levels rise
      and iodine-131 scintigraphy is negative: surgical resection may be appropriate.
      Nonetheless FDG PET should be performed more widely and earlier: the initial
      presence of foci positive for FDG is a major predictor of shorter survival, and
      most cancer lesions take up either iodine or FDG. In follow-up of medullary
      carcinoma, FDG PET detects residual tissue better than any other scintigraphic
      procedures, especially when serum levels of CEA (carcinoembryonic antigen) are
      rising rapidly. FDOPA PET seems to have better sensitivity than FDG-PET and may
      be useful in occult recurrence, as three case reports indicate.

PMID- 16969335
TI  - [PET in primary pulmonary or pleural cancer].
AB  - In our hospital as in many others, primary lung cancer is the most frequent
      indication for FDG PET. Studies have assessed the clinical utility of this
      imaging modality in characterizing solitary pulmonary nodules or masses, initial
      staging, defining tumor volume in radiotherapy and searching for recurrence of or
      restaging non-small cell carcinoma; studies are currently underway to evaluate
      its use in early assessment of chemotherapy response. Small cell lung cancer has
      a high FDG uptake and PET/CT can be useful for rapid staging. False negative
      results may be due to pure bronchioloalveolar carcinomas and endocrine tumors.
      FDG-PET will certainly play a more important role in the diagnosis and follow-up
      of pleural cancers in the future. An unexpected positive FDG PET focus should be
      considered as a warning, but histological proof should precede any irrevocable
      decisions.

PMID- 16969336
TI  - [Scleromyxedema].

PMID- 16969337
TI  - [Invention of Sabouraud agar: progress in medical mycology].

PMID- 16969338
TI  - Principles of microRNA regulation of a human cellular signaling network.
AB  - MicroRNAs (miRNAs) are endogenous approximately 22-nucleotide RNAs, which
      suppress gene expression by selectively binding to the 3'-noncoding region of
      specific messenger RNAs through base-pairing. Given the diversity and abundance
      of miRNA targets, miRNAs appear to functionally interact with various components
      of many cellular networks. By analyzing the interactions between miRNAs and a
      human cellular signaling network, we found that miRNAs predominantly target
      positive regulatory motifs, highly connected scaffolds and most downstream
      network components such as signaling transcription factors, but less frequently
      target negative regulatory motifs, common components of basic cellular machines
      and most upstream network components such as ligands. In addition, when an
      adaptor has potential to recruit more downstream components, these components are
      more frequently targeted by miRNAs. This work uncovers the principles of miRNA
      regulation of signal transduction networks and implies a potential function of
      miRNAs for facilitating robust transitions of cellular response to extracellular
      signals and maintaining cellular homeostasis.

PMID- 16969339
TI  - An integrated systems approach for understanding cellular responses to gamma
      radiation.
AB  - Cellular response to stress entails complex mRNA and protein abundance changes,
      which translate into physiological adjustments to maintain homeostasis as well as
      to repair and minimize damage to cellular components. We have characterized the
      response of the halophilic archaeon Halobacterium salinarum NRC-1 to (60)Co
      ionizing gamma radiation in an effort to understand the correlation between
      genetic information processing and physiological change. The physiological
      response model we have constructed is based on integrated analysis of temporal
      changes in global mRNA and protein abundance along with protein-DNA interactions
      and evolutionarily conserved functional associations. This systems view reveals
      cooperation among several cellular processes including DNA repair, increased
      protein turnover, apparent shifts in metabolism to favor nucleotide biosynthesis
      and an overall effort to repair oxidative damage. Further, we demonstrate the
      importance of time dimension while correlating mRNA and protein levels and
      suggest that steady-state comparisons may be misleading while assessing dynamics
      of genetic information processing across transcription and translation.

PMID- 16969340
TI  - Systematic genetics swims forward elegantly.

PMID- 16969342
TI  - Will Rogers revisited: prospective observational study of survival of 3592
      patients with colorectal cancer according to number of nodes examined by
      pathologists.
AB  - To investigate the relationship between survival in colorectal cancer patients
      and the number of lymph nodes examined by a pathologist, previously attributed to
      stage migration, we used data from a cohort of 5174 colorectal cancer patients
      recruited between September 1991 and August 1994, and followed-up for 5 years. We
      selected cases with data present on all prognostic variables, and stratified them
      into three groups by number of nodes examined. We made a multivariate survival
      comparison using a Cox regression model. In all, there were 3592 cases with data
      present on all prognostic variables. Patients who had >10 nodes identified had a
      significant survival advantage over those who had 5-10 identified, who had in
      turn a similar advantage over those with 0-4 identified (P<0.001). This effect
      was present in the whole group and at all Dukes' stages, although statistically
      significant only in stages B (P=0.004) and C (P=0.019). The effect remained after
      adjustment in a Cox regression model in which the mean number of nodes taken out
      by each surgical firm did not predict survival. In a sub-group with data on
      lymphocytic infiltration into the primary tumour a survival advantage was noted
      in those with prominent rather than mild infiltration (P<0.001): the former also
      tended to have more nodes found (P=0.015). Stage migration alone cannot explain
      these results, as survival advantages are noted across the whole population
      independent of stage. Lymphocytic infiltration into the primary tumour is
      prognostically important, and is associated with the number of nodes found.
      Reactive enlargement of lymph nodes in the mesentery may make them easier to
      find, reflect immune response to the tumour, and thus indirectly impact upon
      survival.

PMID- 16969341
TI  - When transcriptome meets metabolome: fast cellular responses of yeast to sudden
      relief of glucose limitation.
AB  - Within the first 5 min after a sudden relief from glucose limitation,
      Saccharomyces cerevisiae exhibited fast changes of intracellular metabolite
      levels and a major transcriptional reprogramming. Integration of transcriptome
      and metabolome data revealed tight relationships between the changes at these two
      levels. Transcriptome as well as metabolite changes reflected a major investment
      in two processes: adaptation from fully respiratory to respiro-fermentative
      metabolism and preparation for growth acceleration. At the metabolite level, a
      severe drop of the AXP pools directly after glucose addition was not accompanied
      by any of the other three NXP. To counterbalance this loss, purine biosynthesis
      and salvage pathways were transcriptionally upregulated in a concerted manner,
      reflecting a sudden increase of the purine demand. The short-term dynamics of the
      transcriptome revealed a remarkably fast decrease in the average half-life of
      downregulated genes. This acceleration of mRNA decay can be interpreted both as
      an additional nucleotide salvage pathway and an additional level of glucose
      induced regulation of gene expression.

PMID- 16969343
TI  - Vinorelbine plus trastuzumab combination as first-line therapy for HER 2-positive
      metastatic breast cancer patients: an international phase II trial.
AB  - The aim of this international phase II trial was to determine the efficacy and
      safety profile of weekly vinorelbine plus trastuzumab as first-line chemotherapy
      for women with HER 2-overexpressing metastatic breast cancer. Sixty-nine patients
      with tumours overexpressing HER 2 received vinorelbine: 30 mg m-2 week-1 and
      trastuzumab: 4 mg kg-1 on day 1 as a loading dose followed by 2 mg kg-1 week-1
      starting on day 8. Sixty-two patients were evaluable for response and 69 patients
      were evaluable for toxicity. The overall response rate was 62.9%. The median time
      to response was 8.4 weeks, the median duration of response was 17.5 months, the
      median progression-free survival was 9.9 months (95% CI, 5.6-12.1) and the one
      year progression-free survival was 39.1%. The median survival for all patients
      was 23.7 months (95% CI, 18.4-32.6). This regimen was safe: grade 3-4 neutropenia
      were observed over 17.7% of courses in 83.8% of patients, with only two episodes
      of febrile neutropenia (0.1%) in two patients (2.9%). Only one patient
      discontinued treatment due to grade 3 symptomatic cardiac dysfunction that
      resolved with therapy. Vinorelbine plus trastuzumab is one of the most active
      treatment regimens for patients with HER 2-positive metastatic breast cancer and
      demonstrates a very favourable safety profile allowing prolonged treatment with
      long-term survival. This study has been presented in part at the following
      conferences: The San Antonio Breast Cancer Symposium, San Antonio, TX, USA, 2003;
      The American Society of Clinical Oncology, Orlando, FL, USA, 2005.

PMID- 16969344
TI  - Fatty acid synthase: a novel target for antiglioma therapy.
AB  - High levels of fatty acid synthase (FAS) expression have been observed in several
      cancers, including breast, prostate, colon and lung carcinoma, compared with
      their respective normal tissue. We present data that show high levels of FAS
      protein in human and rat glioma cell lines and human glioma tissue samples, as
      compared to normal rat astrocytes and normal human brain. Incubating glioma cells
      with the FAS inhibitor cerulenin decreased endogenous fatty acid synthesis by
      approximately 50%. Cell cycle analysis demonstrated a time- and dose-dependent
      increase in S-phase cell arrest following cerulenin treatment for 24 h. Further,
      treatment with cerulenin resulted in time- and dose-dependent decreases in glioma
      cell viability, as well as reduced clonogenic survival. Increased apoptotic cell
      death and PARP cleavage were observed in U251 and SNB-19 cells treated with
      cerulenin, which was independent of the death receptor pathway. Overexpressing
      Bcl-2 inhibited cerulenin-mediated cell death. In contrast, primary rat
      astrocytes appeared unaffected. Finally, RNAi-mediated knockdown of FAS leading
      to reduced FAS enzymatic activity was associated with decreased glioma cell
      viability. These findings suggest that FAS might be a novel target for antiglioma
      therapy.

PMID- 16969345
TI  - Gene expression profiling of human ovarian tumours.
AB  - There is currently a lack of reliable diagnostic and prognostic markers for
      ovarian cancer. We established gene expression profiles for 120 human ovarian
      tumours to identify determinants of histologic subtype, grade and degree of
      malignancy. Unsupervised cluster analysis of the most variable set of expression
      data resulted in three major tumour groups. One consisted predominantly of benign
      tumours, one contained mostly malignant tumours, and one was comprised of a
      mixture of borderline and malignant tumours. Using two supervised approaches, we
      identified a set of genes that distinguished the benign, borderline and malignant
      phenotypes. These algorithms were unable to establish profiles for histologic
      subtype or grade. To validate these findings, the expression of 21 candidate
      genes selected from these analyses was measured by quantitative RT-PCR using an
      independent set of tumour samples. Hierarchical clustering of these data resulted
      in two major groups, one benign and one malignant, with the borderline tumours
      interspersed between the two groups. These results indicate that borderline
      ovarian tumours may be classified as either benign or malignant, and that this
      classifier could be useful for predicting the clinical course of borderline
      tumours. Immunohistochemical analysis also demonstrated increased expression of
      CD24 antigen in malignant versus benign tumour tissue. The data that we have
      generated will contribute to a growing body of expression data that more
      accurately define the biologic and clinical characteristics of ovarian cancers.

PMID- 16969346
TI  - Phase II study of SPI-77 (sterically stabilised liposomal cisplatin) in advanced
      non-small-cell lung cancer.
AB  - To determine the efficacy and tolerability of SPI-77 (sterically stabilised
      liposomal cisplatin) at three dose levels in patients with advanced non-small
      cell lung cancer (NSCLC). Patients had Stage IIIB or IV NSCLC and were chemo
      naive, and Eastern Oncology Cooperative Group 0-2. The first cohort received SPI
      77 at 100 mg m-2, the second 200 mg m-2 and the final cohort 260 mg m-2. Patients
      had also pharmacokinetics and analysis of leucocyte platinum (Pt)-DNA adducts
      performed. Twenty-six patients were treated, with 22 patients being evaluable for
      response. Only one response occurred at the 200 mg m-2 dose level for an overall
      response rate of 4.5% (7.1% at >or=200 mg m-2). No significant toxicity was noted
      including nephrotoxicity or ototoxicity aside from two patients with Grade 3
      nausea. No routine antiemetics or hydration was used. The pharmacokinetic profile
      of SPI-77 was typical for a liposomally formulated drug, and the AUC appeared to
      be proportional to the dose of SPI-77. Plasma Pt levels and leucocyte DNA adduct
      levels did not appear to rise with successive doses. SPI-77 demonstrates only
      modest activity in patients with NSCLC.

PMID- 16969347
TI  - Antineoplastic effects of rosiglitazone and PPARgamma transactivation in
      neuroblastoma cells.
AB  - Neuroblastoma (NB) is the most common extracranial solid tumour in infants.
      Unfortunately, most children present with advanced disease and have a poor
      prognosis. In the present study, we evaluated the role of the peroxisome
      proliferator-activated receptor gamma (PPARgamma) agonist rosiglitazone (RGZ) in
      two NB cell lines (SK-N-AS and SH-SY5Y), which express PPARgamma. Rosiglitazone
      decreased cell proliferation and viability to a greater extent in SK-N-AS than in
      SH-SY5Y. Furthermore, 20 microM RGZ significantly inhibited cell adhesion,
      invasiveness and apoptosis in SK-N-AS, but not in SH-SY5Y. Because of the
      different response of SK-N-AS and SH-SY5Y cells to RGZ, the function of PPARgamma
      as a transcriptional activator was assessed. Noticeably, transient transcription
      experiments with a PPARgamma responsive element showed that RGZ induced a three
      fold increase of the reporter activity in SK-N-AS, whereas no effect was observed
      in SH-SY5Y. The different PPARgamma activity may be likely due to the markedly
      lower amount of phopshorylated (i.e. inactive) protein observed in SK-N-AS. To
      our knowledge, this is the first demonstration that the differential response of
      NB cells to RGZ may be related to differences in PPARgamma transactivation. This
      finding indicates that PPARgamma activity may be useful to select those patients,
      for whom PPARgamma agonists may have a beneficial therapeutic effect.

PMID- 16969348
TI  - Expression of PPARdelta in multistage carcinogenesis of the colorectum:
      implications of malignant cancer morphology.
AB  - Whether peroxisome proliferator-activated receptor (PPAR) delta is a good target
      for the chemoprevention and/or treatment of colorectal cancer (CRC) remains
      controversial. Our goal was to examine PPARdelta expression in multistage
      carcinogenesis of the colorectum and to assess the relevance of PPARdelta in CRC.
      Immunohistochemical analysis indicated that PPARdelta expression increased from
      normal mucosa to adenomatous polyps to CRC. In cancer tissues, the PPARdelta
      protein was accumulated only in those cancer cells with highly malignant
      morphology, as represented by a large-sized nucleus, round-shaped nucleus, and
      presence of clear nucleoli. Interestingly, the cancer tissue often contained both
      PPARdelta-positive and -negative areas, each retaining their respective specific
      morphological features. Moreover, this pattern persisted even when PPARdelta
      positive and -negative cells were aligned next to each other within a single
      cancer nest or gland and was present in the majority of CRC cases.
      Immunohistochemistry for Ki-67 proliferation marker showed no significant
      correlation between Ki-67 and PPARdelta in CRC samples. Based on Western blot
      analysis and quantitative RT-PCR, high PPARdelta protein expression correlated
      with high PPARdelta mRNA levels. Peroxisome proliferator-activated receptor delta
      may have a supporting role in tumorigenesis, and the close association between
      PPARdelta expression and malignant morphology of CRC cells suggests a pivotal
      role in cancer tissue.

PMID- 16969349
TI  - Genetic and epigenetic changes in primary metastatic and nonmetastatic colorectal
      cancer.
AB  - Colorectal cancer (CRC) develops as multistep process, which involves genetic and
      epigenetic alterations. K-Ras, p53 and B-Raf mutations and RASSF1A, E-Cadherin
      and p16INK4A promoter methylation were investigated in 202 CRCs with and without
      lymph node and/or liver metastasis, to assess whether gene abnormalities are
      related to a metastogenic phenotype. K-Ras, B-Raf and p53 mutations were detected
      in 27, 3 and 32% of the cases, with K-Ras mutations significantly associated with
      metastatic tumour (P=0.019). RASSF1A, E-Cadherin and p16INK4A methylation was
      documented in 20, 44 and 33% of the cases with p16INK4A significantly associated
      with metastatic tumours (P=0.001). Overall, out of 202 tumours, 34 (17%) did not
      show any molecular change, 125 (62%) had one or two and 43 (21%) three or more.
      Primary but yet metastatic CRCs were prevalent in the latter group (P=0.023)
      where the most frequent combination was one genetic (K-Ras in particular) and two
      epigenetic alterations. In conclusion, this analysis provided to detect some
      molecular differences between primary metastatic and nonmetastatic CRCs, with K
      Ras and p16INK4A statistically altered in metastatic tumours; particular gene
      combinations, such as coincidental K-Ras mutation with two methylated genes are
      associated to a metastogenic phenotype.

PMID- 16969350
TI  - Randomised study of adjuvant chemotherapy for completely resected p-stage I-IIIA
      non-small cell lung cancer.
AB  - We evaluated the therapeutic usefulness of adjuvant chemotherapy in patients with
      completely resected non-small cell lung cancer (NSCLC). We also examined the
      relation between DNA ploidy pattern and the response to chemotherapy. A total of
      267 patients with NSCLC (pathologically documented stage I, II, or IIIA)
      underwent complete resection, and DNA ploidy pattern was analysed. Patients with
      stage I disease (n=172) were randomly assigned to receive surgery alone (group A)
      or surgery followed by adjuvant chemotherapy (UFT (oral anti-cancer drug, a
      combination of Uracil and Tegaful) 400 mg day-1 for 1 year after surgery; group
      B). Stage II or IIIA disease patients (n=95) were randomly assigned to surgery
      alone (group C) or surgery followed by chemotherapy (two 28-day courses of
      cisplatin 80 mg m-2 on day 1 plus vindesine 3 mg m-2 on days 1 and 8, followed by
      UFT 400 mg day-1 for at least 1 year; group D). Eight-year overall survival rate
      in patients with stage I disease was 74.2% (95% confidence interval (CI): 64.4
      84.0%) in group B and 57.6% (95% CI: 46.4-68.8%) in group A (P=0.045 by log-rank
      test). In patients with stage II and IIIA disease, no difference was found
      between groups C and D. Analysis according to DNA ploidy pattern revealed no
      difference between the groups. Postoperative chemotherapy with UFT was suggested
      to be useful in patients with completely resected stage I NSCLC. No difference
      was seen in relation to DNA pattern in any treatment group.

PMID- 16969351
TI  - Socioeconomic and geographic determinants of survival of patients with digestive
      cancer in France.
AB  - Using a multilevel Cox model, the association between socioeconomic and
      geographical aggregate variables and survival was investigated in 81 268 patients
      with digestive tract cancer diagnosed in the years 1980-1997 and registered in 12
      registries in the French Network of Cancer Registries. This association differed
      according to cancer site: it was clear for colon (relative risk (RR)=1.10 (1.04
      1.16), 1.10 (1.04-1.16) and 1.14 (1.05-1.23), respectively, for distances to
      nearest reference cancer care centre between 10 and 30, 30 and 50 and more than
      90 km, in comparison with distance of less than 10 km; P-trend=0.003) and rectal
      cancer (RR=1.09 (1.03-1.15), RR=1.08 (1.02-1.14) and RR=1.12 (1.05-1.19),
      respectively, for distances between 10 and 30 km, 30 and 50 km and 50 and 70 km,
      P-trend=0.024) (n=28 010 and n=18 080, respectively) but was not significant for
      gall bladder and biliary tract cancer (n=2893) or small intestine cancer
      (n=1038). Even though the influence of socioeconomic status on prognosis is
      modest compared to clinical prognostic factors such as histology or stage at
      diagnosis, socioeconomic deprivation and distance to nearest cancer centre need
      to be considered as potential survival predictors in digestive tract cancer.

PMID- 16969353
TI  - Do delays between diagnosis and surgery in resectable oesophageal cancer affect
      survival? A study based on West Midlands cancer registration data.
AB  - This retrospective study investigates if delays between the diagnosis of cancer
      of the oesophagus and surgical resection influence long-term survival. Data held
      by the West Midlands Cancer Intelligence Unit on 800 patients who underwent
      oesophagectomy for a diagnosis of cancer of the oesophagus or oesophagogastric
      junction between 1995 and 2000 were reviewed. Six hundred and thirty-two patients
      treated with curative intention and who had not received neo-adjuvant treatment
      in the form of radio- or chemotherapy were included in the analysis. The time
      interval between histological diagnosis and surgical resection was stratified
      into four groups: less than 3, 3-6, 6-9 and more than 9 weeks. The Cox
      proportional hazard model was used to test for the independent effect of delays.
      The results showed no difference in long-term survival according to the delay
      between histological diagnosis and surgical resection. On multivariate analysis
      adverse prognostic factors were advanced age, incomplete resection and lymph node
      involvement. Patients with a longer delay had a higher rate of complete tumour
      resection suggesting that they were more appropriately selected for the surgical
      treatment approach. In conclusion we have found no evidence that shorter delays
      from the date of histological diagnosis to surgical resection are beneficial to
      long-term survival.

PMID- 16969352
TI  - Outpatient chemotherapy with gemcitabine and oxaliplatin in patients with biliary
      tract cancer.
AB  - This phase II study was conducted to determine the efficacy and toxicity of a
      gemcitabine (GEM) and oxaliplatin (OX) chemotherapy protocol in patients with
      unresectable biliary tract cancer (BTC). Patients were treated with GEM 1000 mg m
      2 (30 min infusion) on days 1, 8, 15, and OX 100 mg m-2 (2 h infusion) on days 1
      and 15 (gemcitabine and oxaliplatin (GEMOX-3 protocol), repeated every 28 days.
      The data were collected according to the Simon 2-stage design for a single centre
      phase II study (alpha=0.05; beta=0.2). Primary end point was response rate;
      secondary end points were time-to-progression (TTP), median survival, and safety
      profile. Thirty-one patients were enrolled in the study between July 2002 and
      April 2005. Therapeutic responses were as follows: partial response in eight
      patients (26%, 95% confidence interval (CI) 14-44), stable disease in 14 patients
      (45%, 95%CI 29-62), resulting in a disease control rate of 71%. Nine patients
      (29%, 95%CI 16-47) had progressive disease. Median TTP was 6.5 months. Median
      overall survival was 11 months. Common Toxicity Criteria (CTC) Grade 3-4
      toxicities were transient thrombocytopenia (23%), peripheral sensory neuropathy
      (19%), leucopenia (16%), and anaemia (10%). In conclusion the GEMOX-3 protocol is
      active and well tolerated in patients with advanced BTC. It can be applied in an
      outpatient setting with three visits per month only.

PMID- 16969354
TI  - Phase II and pharmacological study of oral paclitaxel (Paxoral) plus ciclosporin
      in anthracycline-pretreated metastatic breast cancer.
AB  - Paclitaxel is an important chemotherapeutic agent for breast cancer. Paclitaxel
      has high affinity for the P-glycoprotein (P-gp) (drug efflux pump) in the
      gastrointestinal tract causing low and variable oral bioavailability. Previously,
      we demonstrated that oral paclitaxel plus the P-gp inhibitor cyclosporin (CsA) is
      safe and results in adequate exposure to paclitaxel. This study evaluates the
      activity, toxicity and pharmacokinetics of paclitaxel combined with CsA in breast
      cancer patients. Patients with measurable metastatic breast cancer were given
      oral paclitaxel 90 mg m-2 combined with CsA 10 mg kg-1 (30 min prior to each
      paclitaxel administration) twice on one day, each week. Twenty-nine patients with
      a median age of 50 years were entered. All patients had received prior
      treatments, 25 had received prior anthracycline-containing chemotherapy and 19
      had three or more metastatic sites. Total number of weekly administrations was
      442 (median: 15/patient) and dose intensity of 97 mg m-2 week-1. Most patients
      needed treatment delay and 17 patients needed dose reductions. In intention to
      treat analysis, the overall response rate was 52%, the median time to progression
      was 6.5 months and overall survival was 16 months. The pharmacokinetics revealed
      moderate inter- and low intrapatient variability. Weekly oral paclitaxel,
      combined with CsA, is active in patients with advanced breast cancer.

PMID- 16969355
TI  - The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic
      melanoma: a phase IIA clinical and biologic study.
AB  - Midostaurin (PKC412A), N-benzoyl-staurosporine, potently inhibits protein kinase
      C alpha (PKCalpha), VEGFR2, KIT, PDGFR and FLT3 tyrosine kinases. In mice,
      midostaurin slows growth and delays lung metastasis of melanoma cell lines. We
      aimed to test midostaurin's safety, efficacy and biologic activity in a Phase IIA
      clinical trial in patients with metastatic melanoma. Seventeen patients with
      advanced metastatic melanoma received midostaurin 75 mg p.o. t.i.d., unless
      toxicity or disease progression supervened. Patient safety was assessed weekly,
      and tumour response was assessed clinically or by CT. Tumour biopsies and plasma
      samples obtained at entry and after 4 weeks were analysed for midostaurin
      concentration, PKC activity and multidrug resistance. No tumour responses were
      seen. Two (12%) patients had stable disease for 50 and 85 days, with minor
      response in one. The median overall survival was 43 days. Seven (41%)
      discontinued treatment with potential toxicity, including nausea, vomiting,
      diarrhoea and/or fatigue. One patient had >50% reduction in PKC activity. Tumour
      biopsies showed two PKC isoforms relatively insensitive to midostaurin, out of
      three patients tested. No modulation of multidrug resistance was demonstrated. At
      this dose schedule, midostaurin did not show clinical or biologic activity
      against metastatic melanoma. This negative trial reinforces the importance of
      correlating biologic and clinical responses in early clinical trials of targeted
      therapies.

PMID- 16969356
TI  - Preoperative elevation of serum C--reactive protein is predictive for prognosis
      in myeloma bone disease after surgery.
AB  - We investigated whether preoperative levels of serum C-reactive protein (CRP) and
      its correlation with tumour clinicopathological findings adds prognostic
      information beyond the time of diagnosis in patients with myeloma bone disease
      (MM) to facilitate the surgical decision-making process. Six hundred and fifty
      eight myeloma patients were evaluated retrospectively for surgery.
      Clinicopathological variables of patients who underwent surgery (n=71) were
      compared between patients with preoperative CRP>or=6 mg l-1 and those with CRP<6
      mg l-1. Univariate and multivariate analyses were performed to identify
      prognostic factors after surgery. Patients with an increase of CRP prior to
      surgery showed inferior survival compared to patients with normal levels.
      Patients with normal CRP levels at diagnosis but elevations prior to surgery do
      seem to have a similar unfavourable overall survival (OS) than patients with an
      increase both, at diagnosis and at surgery. Conversely, patients with normal CRP
      levels prior to surgery still have the best OS, irrespective of their basic
      values. Multivariate analysis revealed preoperative CRP levels above 6 mg l-1
      Lactate dehydrogenase (LDH) above normal, and osteolyses in long weight bearing
      bones as independent predictors of survival. These findings suggest that in
      patients with MM serum levels of CRP increase during disease activity and might
      be significantly correlated with specific disease characteristics including
      adverse prognostic features such as osteolyses in long weight bearing bones.
      Thus, preoperative elevated CRP serum levels might be considered as independent
      predictor of prognosis and could provide additional prognostic information for
      the risk stratification before surgical treatment in patients with myeloma bone
      disease.

PMID- 16969357
TI  - Health behaviour of persons with spinal cord injury.
AB  - STUDY DESIGN: Postal survey. OBJECTIVE: To describe the health behaviour of
      persons with spinal cord injury (SCI) living in the community and the
      relationships between health behaviour, respondent/injury characteristics, and
      health-related variables: the presence and number of secondary impairments,
      readmissions in rehabilitation centre and hospital, and perceived health.
      SETTING: Members of the Dutch Association of Patients with SCI. METHODS: The
      frequency of health behaviours, that delay or prevent secondary impairments, was
      assessed by means of a 22-item, self-report questionnaire. The questionnaire was
      also focused on 13 secondary impairments. RESULTS: The frequency of engaging in
      health behaviour varied considerably between the respondents. Variance was
      observed between and within the health behaviours measured. The respondents did
      not frequently engage in pressure relief methods when sitting/driving in their
      wheelchair. Almost no statistical differences were observed between health
      behaviour of subgroups of respondents based on respondent/injury characteristics.
      However, the total health behaviour scores increased significantly with
      increasing age and pressure sore prevention was significantly more applied in
      persons with a complete lesion. Health behaviour was significantly more applied
      in respondents who had one or more secondary impairments. CONCLUSION: As
      secondary impairments are prevalent among persons with SCI and education on a
      healthy lifestyle is a core component of every rehabilitation programme, it is of
      great importance to rigorously test the efficacy of health behaviours promoted
      during rehabilitation. Therefore, longitudinal research is recommended.

PMID- 16969359
TI  - Changes in BMI modulate age-associated changes in sex hormone binding globulin
      and total testosterone, but not bioavailable testosterone in young adult men: the
      CARDIA Male Hormone Study.
AB  - OBJECTIVES: To compare age-associated 8-year changes in total testosterone,
      calculated bioavailable testosterone and sex hormone binding globulin (SHBG)
      across five groups of men stratified according to change in body mass index (BMI)
      (i.e., BMI stable (+/-0.69 kg/m(2)), decreased (-0.7 kg/m(2)), increased
      minimally (0.7-1.74 kg/m(2)), increased moderately (1.75-3.19 kg/m(2)) and
      increased most (> or =3.20 kg/m(2))). DESIGN: Eight-year longitudinal cohort
      study. SUBJECTS: Four hundred and seventy-four black and 695 white men, aged 24
      31 years at the time of the first hormone measurement. MEASUREMENTS: Aging
      related changes in serum SHBG, total testosterone and bioavailable testosterone.
      RESULTS: SHBG significantly increased with age for men whose BMI decreased, and
      there were progressively smaller increases for men whose BMI was stable, or whose
      BMI increased minimally or moderately (range 1.1-0.3 nM per year, P< or =0.03,
      respectively). There was no age relationship with SHBG among men whose BMI
      increased most. Total testosterone did not change with age for men whose BMI
      decreased, was stable or increased minimally, but for men whose BMI increased
      moderately and most there was a graded decrease in total testosterone with age
      (beta=-0.2 and -0.4 nM per year, respectively, P< or =0.005). However,
      bioavailable testosterone decreased with age to a similar extent across all
      groups. CONCLUSIONS: These results suggest that changes in BMI during young
      adulthood modulate age-related changes in SHBG and total testosterone, but not
      bioavailable testosterone.

PMID- 16969360
TI  - Children with a TV in their bedroom at higher risk for being overweight.
AB  - OBJECTIVE: We examined having a TV in the bedroom as a risk factor for child
      overweight. DESIGN: Cross-sectional study. SETTING: School- and telephone-based
      surveys in New Hampshire and Vermont between 2002 and 2004. PARTICIPANTS: Two
      thousand three hundred and forty-three children enrolled in public schools, aged
      9-12 years, and one of their parents. MAIN EXPOSURES: The child having a TV in
      the bedroom. MAIN OUTCOME MEASURES: Age- and gender-standardized child body mass
      index (zBMI). Overweight was defined as equal to or above the 95th percentile for
      zBMI. RESULTS: Overall, 22.3% (N=523) of the children were overweight, and almost
      half of all children (48.2%, N=1130) had a TV in their bedroom. Children with a
      TV in their bedroom had a higher zBMI and were significantly more likely to be
      overweight compared to those without a TV in their bedroom (27.3 versus 17.7%,
      respectively; P<0.05). After controlling for sociodemographics, physical
      activity, frequency of TV or movie watching and internet use, children with a TV
      in their bedroom who watched at least one session of TV or movies per day were
      more likely to be overweight compared to those without a TV in their bedroom
      (odds ratio=1.32, 95% confidence interval: 1.03, 1.70). CONCLUSIONS: Having a TV
      in the bedroom is a risk factor for child overweight, independent of reported
      physical activity, participation in team sports, TV or movie watching time and
      internet use at home. Further study is needed to fully understand the mechanism
      by which having a TV in the bedroom increases children's risk for overweight.

PMID- 16969361
TI  - An open-label pilot study of the combination therapy of metformin and fluoxetine
      for weight reduction.
AB  - BACKGROUND: Obesity is a very important risk factor for cardiovascular disease,
      type 2 diabetes mellitus, hypertension, osteoarthritis, fatty liver, metabolic
      syndrome and respiratory problems. Many weight-reducing drugs cannot be used in
      obese patients because of numerous complications. Fluoxetine, an antidepressant,
      and metformin, an antidiabetic drug, reduce weight as their side effect, but the
      potency of each drug is not always enough. Here, we studied the effects of
      combination therapy of them for weight reduction in obese women. MATERIALS AND
      METHODS: This study was designed as an open, prospective, controlled clinical
      trial. Obese and overweight patients referred to obesity clinics were first put
      under a diet and behavior therapy education program before being invited to this
      study. The patients who accepted drug therapy were put in the case group. Those
      who did not accept drug therapy were put in the control group. Fluoxetine, 20 mg
      daily, and metformin, 500 mg three times daily, were prescribed to the
      participants. Weight and body mass index (BMI) changes within case and control
      groups were analyzed by paired t-tests and between groups by t-testing. Side
      effects were evaluated by interview and questionnaire. SUBJECTS: Two hundred and
      three patients were referred to obesity clinics. Of these, 177 were female with
      91 being volunteers for this study. Of this 91, 66 were in the case group and 25
      in the control group. RESULTS: In a 6.68-month period, a 7.89 kg decrease in
      weight (9.32%) and a 3.43 U decrease in BMI (10.14%) were observed in
      participants of the case group that was statistically significant (P<0.0001). The
      participants of the control group were followed for a mean period of 8.12 months.
      In this period, the participants of the control group showed a 0.48 kg decrease
      in weight (0.52%) and a 0.11 U decrease in BMI (0.42%). This was not significant.
      No serious side effects of the drugs were observed in the case group. CONCLUSION:
      This open-label pilot study of combination therapy of metformin and fluoxetine
      gave encouraging weight reduction, and these results suggest the need for a
      randomized double-blind clinical trial comparing the two components and the
      combination to placebo.

PMID- 16969362
TI  - Genetic susceptibility to Tardive Dyskinesia in chronic schizophrenia subjects:
      V. Association of CYP1A2 1545 C>T polymorphism.
AB  - Tardive dyskinesia (TD) is an iatrogenic disorder observed in approximately 20
      30% of schizophrenia patients on long-term treatment with typical antipsychotic
      drugs. CYP1A2 is involved in the metabolism of atypical antipsychotic drugs such
      as clozapine and olanzapine. It is not directly involved in the metabolism of
      typical antipsychotic drugs, but gains importance when the schizophrenia patients
      are under long-term chronic treatment, acting as a low-affinity high-capacity
      metabolizing enzyme. In this study, we have completely sequenced the coding
      region to ascertain the presence of common coding polymorphisms and their role if
      any in susceptibility to TD and schizophrenia. Four previously reported
      polymorphisms, CYP1A2*1F (intron A), rs2472304 & rs3743484 (intron D) and
      rs2470890 (CYP1A2 1545 C>T) in exon 7 were identified. We further investigated
      whether the CYP1A2 1545 C>T polymorphism has any role to play in susceptibility
      to TD and in schizophrenia per se. Association of this single nucleotide
      polymorphism with TD (P=0.03) and schizophrenia (P=0.04) was observed, but was
      rendered insignificant after corrections for multiple comparisons.

PMID- 16969363
TI  - Use of pairwise marker combination and recursive partitioning in a
      pharmacogenetic genome-wide scan.
AB  - The objective of pharmacogenetic research is to identify a genetic marker, or a
      set of genetic markers, that can predict how a given person will respond to a
      given medicine. To search for such marker combinations that are predictive of
      adverse drug events, we have developed and applied two complementary methods to a
      pharmacogenetic study of the hypersensitivity reaction (HSR) associated with
      treatment with abacavir, a medicine that is used to treat HIV-infected patients.
      Our results show that both of these methods can be used to uncover potentially
      useful predictive marker combinations. The pairwise marker combination method
      yielded a collection of marker pairs that featured a spectrum of sensitivities
      and specificities. Recursive partitioning results led to the genetic delineation
      of multiple risk categories, including those with extremely high and extremely
      low risk of HSR. These methods can be readily applied in pharmacogenetic
      candidate gene studies as well as in genome-wide scans.

PMID- 16969364
TI  - ABCB1 genotype and PGP expression, function and therapeutic drug response: a
      critical review and recommendations for future research.
AB  - The product of the ABCB1 gene, P-glycoprotein (PGP), is a transmembrane active
      efflux pump for a variety of drugs. It is a putative mechanism of multidrug
      resistance in a range of diseases. It is postulated that ABCB1 polymorphisms
      contribute to variability in PGP function, and that therefore multidrug
      resistance is, at least in part, genetically determined. However, studies of
      ABCB1 genotype or haplotype and PGP expression, activity or drug response have
      produced inconsistent results. This critical review of ABCB1 genotype and PGP
      function, including mRNA expression, PGP-substrate drug pharmacokinetics and drug
      response, highlights methodological limitations of existing studies, including
      inadequate power, potential confounding by co-morbidity and co-medication,
      multiple testing, poor definition of disease phenotype and outcomes, and analysis
      of multiple drugs that might not be PGP substrates. We have produced
      recommendations for future research that will aid clarification of the
      association between ABCB1 genotypes and factors related to PGP activity.

PMID- 16969365
TI  - Genetic variation at the CYP2C locus and its association with torsemide
      biotransformation.
AB  - In 97 unselected volunteers and two additional homozygous carriers of CYP2C9(*)3,
      we investigated the oral clearance of torsemide in relation to 37 polymorphisms
      at the CYP2C gene locus. Torsemide total oral clearance was linearly associated
      with the number of CYP2C9(*)3 alleles (geometric mean: 59, 40 and 20 ml/min in
      carriers of no, one and two alleles) and so were the methyl- and ring
      hydroxylation but not the carboxylation clearance. Haplotypes including the
      CYP2C9(*)3 allele were similarly associated with the clearances but no other
      variant and no haplotype not including the CYP2C9(*)3 variant. The extended
      haplotype length (EHL) of the CYP2C9 haplotypes was positively associated with
      higher activity of the gene product. Torsemide total oral clearance was
      predictable with r(2)=82.1% using plasma concentrations at 0.5, 1, 2 and 24 h. In
      conclusion, torsemide's biotransformation strongly depended on the CYP2C9(*)3
      variant but no other. Higher clearance CYP2C9 haplotypes appear to be
      evolutionarily selected.

PMID- 16969366
TI  - Genome-wide scan supports the existence of a susceptibility locus for
      schizophrenia and bipolar disorder on chromosome 15q26.
AB  - Schizophrenia (SZ) and bipolar disorder (BPD) are two severe psychiatric diseases
      with a strong genetic component. In agreement with the 'continuum theory', which
      suggests an overlap between these disorders, the existence of genes that affect
      simultaneously susceptibility to SZ and BPD has been hypothesized. In this study
      we performed a 7.5 cM genome scan in a sample of 16 families affected by SZ and
      BPD, all originating from the same northeast Italian population. Using both
      parametric and non-parametric analyses we identified linkage peaks on four
      regions (1p, 1q, 4p and 15q), which were then subjected to a follow-up study with
      an increased marker density. The strongest linkage was obtained on chromosome
      15q26 with a non-parametric linkage of 3.05 for marker D15S1014 (nominal
      P=0.00197). Interestingly, evidence for linkage with the same marker has been
      reported previously by an independent study performed on SZ and BPD families from
      Quebec. In this region, the putative susceptibility gene ST8SIA2 (also known as
      SIAT8B) was recently associated with SZ in a Japanese sample. However, our allele
      frequency analyses of the two single-nucleotide polymorphisms (SNPs) with
      putative functional outcome (rs3759916 and rs3759914) suggest that these
      polymorphisms are unlikely to be directly involved in SZ in our population. In
      conclusion, our results support the presence of a gene in 15q26 that influences
      the susceptibility to both SZ and BPD.

PMID- 16969367
TI  - Valproate protects dopaminergic neurons in midbrain neuron/glia cultures by
      stimulating the release of neurotrophic factors from astrocytes.
AB  - Valproate (VPA), one of the mood stabilizers and antiepileptic drugs, was
      recently found to inhibit histone deacetylases (HDAC). Increasing reports
      demonstrate that VPA has neurotrophic effects in diverse cell types including
      midbrain dopaminergic (DA) neurons. However, the origin and nature of the
      mediator of the neurotrophic effects are unclear. We have previously demonstrated
      that VPA prolongs the survival of midbrain DA neurons in lipopolysaccharide (LPS)
      treated neuron-glia cultures through the inhibition of the release of pro
      inflammatory factors from microglia. In this study, we report that VPA
      upregulates the expression of neurotrophic factors, including glial cell line
      derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF)
      from astrocytes and these effects may play a major role in mediating VPA-induced
      neurotrophic effects on DA neurons. Moreover, VPA pretreatment protects midbrain
      DA neurons from LPS or 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity.
      Our study identifies astrocyte as a novel target for VPA to induce neurotrophic
      and neuroprotective actions in rat midbrain and shows a potential new role of
      cellular interactions between DA neurons and astrocytes. The neurotrophic and
      neuroprotective effects of VPA also suggest a utility of this drug for treating
      neurodegenerative disorders including Parkinson's disease. Moreover, the
      neurotrophic effects of VPA may contribute to the therapeutic action of this drug
      in treating bipolar mood disorder that involves a loss of neurons and glia in
      discrete brain areas.

PMID- 16969368
TI  - Meta-analysis supports association between serotonin transporter (5-HTT) and
      suicidal behavior.
AB  - Suicidal behavior, which ranks among the top 10 causes of death worldwide, is an
      important public-health problem and a psychiatric disorder, which has been the
      subject of considerable study. Studies have shown association between the
      serotonin transporter (5-HTT) gene and suicidal behavior, although a proportion
      of alternative studies have produced contrary results both in terms of positive
      and negative findings, possibly reflecting inadequate statistical power and the
      use of different populations. Using the cumulative data from recent years in both
      European and, more particularly, Asian populations, this updated meta-analysis
      seeks to examine whether the aggregate data provide evidence of statistical
      significance, and to clarify the contradictory findings suggested by previous
      studies. It covers all published studies using multiple research methods up to
      January 2006. Compared with a previous meta-analysis, which found no association
      between the 5-HTTLPR polymorphism and suicidal behavior (P=0.38), the current
      results (39 studies) suggest a significant association with a P-value of 0.0068
      (overall odds ratio=0.88 (0.8,0.97)), and supports the involvement of the brain 5
      HTT in the pathogenesis of suicidal behavior.

PMID- 16969369
TI  - Localization of Ang-1, -2, Tie-2, and VEGF expression at endothelial-pericyte
      interdigitation in rat angiogenesis.
AB  - Endothelial cells and pericytes play critical role in angiogenesis, which is
      controlled, in part, by the angiopoietin (Ang)/Tie-2 system and vascular
      endothelial growth factor (VEGF). Here, we investigated Ang, Tie-2, and VEGF
      expression within endothelial cells and pericyte interdigitations (EPI), which
      consist of cytoplasmic projections of pericytes and corresponding endothelial
      indentations. After subcutaneous implantation of a thermoreversible gelation
      polymer disc in rats, the capillary density was low on day 5, increased to a peak
      on day 7, and then decreased on days 10-20. A small number of EPI were observed
      on day 5, then increased sharply to a peak on day 10, but had decreased on day
      20. Light and electron microscopy immunohistochemical and RNA in situ
      hybridization analyses revealed that Tie-2 localized at endothelial cells, and
      Ang-2 localized at endothelial cells and pericytes, while Ang-1 and VEGF
      localized at pericytes, and Ang-1 was most intensely observed at EPI of
      pericytes. Conventional quantitative RT-PCR and Western blot analyses revealed
      that the level of Ang-1 was low on days 5-7, then increased on days 10-20, while
      the level of VEGF was high on days 5-10, but had decreased on day 20. The level
      of Ang-2 remained high and Tie-2 remained at the level of the control on days 5
      20. The present study showed that the angiogenic phase might be initiated by
      increases in Ang-2 and VEGF, while the microvessel maturation phase might be
      initiated by a relative increase in Ang-1 and a decrease in VEGF. Moreover, EPI
      might serve as a pathway for the Ang-1/Tie-2 system, with VEGF promoting pericyte
      recruitment for microvascular integrity.

PMID- 16969370
TI  - Maternal microchimerism in healthy adults in lymphocytes, monocyte/macrophages
      and NK cells.
AB  - During pregnancy some maternal cells reach the fetal circulation. Microchimerism
      (Mc) refers to low levels of genetically disparate cells or DNA. Maternal Mc has
      recently been found in the peripheral blood of healthy adults. We asked whether
      healthy women have maternal Mc in T and B lymphocytes, monocyte/macrophages and
      NK cells and, if so, at what levels. Cellular subsets were isolated after
      fluorescence activated cell sorting. A panel of HLA-specific real-time
      quantitative PCR assays was employed targeting maternal-specific HLA sequences.
      Maternal Mc was expressed as the genome equivalent (gEq) number of microchimeric
      cells per 100,000 proband cells. Thirty-one healthy adult women probands were
      studied. Overall 39% (12/31) of probands had maternal Mc in at least one cellular
      subset. Maternal Mc was found in T lymphocytes in 25% (7/28) and B lymphocytes in
      14% (3/21) of probands. Maternal Mc levels ranged from 0.9 to 25.6 and 0.9 to
      25.3 gEq/100,000 in T and B lymphocytes, respectively. Monocyte/macrophages had
      maternal Mc in 16% (4/25) and NK cells in 28% (5/18) of probands with levels from
      0.3 to 36 and 1.8 to 3.2 gEq/100,000, respectively. When compared to fetal Mc, as
      assessed by quantification of male DNA in women with sons, maternal Mc was
      substantially less prevalent in all cellular subsets; fetal Mc prevalence in T
      and B lymphocytes, monocyte/macrophages and NK cells was 58, 75, 50 and 62%
      (P=0.01, P=0.005, P=0.04, P=0.05) respectively. In summary, maternal Mc was
      identified among lymphoid and myeloid compartments of peripheral blood in healthy
      adult women. Maternal Mc was less frequent than fetal Mc in all cellular subsets
      tested. Studies are needed to investigate the immunological effects and function
      of maternal Mc and to explore whether maternal Mc in cellular subsets has
      biological effects on her progeny.

PMID- 16969371
TI  - Albumin marks pseudopodia of astrocytoma cells responding to hepatocyte growth
      factor or serum.
AB  - It is well accepted that dysfunction in the blood brain barrier (BBB) allows
      permeation of albumin from the bloodstream into astrocytic brain tumors,
      especially glioblastomas, the most aggressive astrocytomas. In vitro, bovine
      serum albumin (BSA) aids functional cell assays by maintaining cytokines and
      growth factors in solution and delivering its cargo of fatty acids. Earlier, we
      showed that BSA was prominent in lysates prepared from pseudopodia formed by U87
      astrocytoma cells. The present studies investigated the association of albumin
      with pseudopodia formed by U87 and LN229 astrocytoma cells. With hepatocyte
      growth factor (HGF) stimulation, cell migration was enhanced and BSA, especially
      its dimerized form, was prominent in pseudopodia compared to unmigrated cells on
      one-dimensional gels and immunoblots. When lysates were equalized for levels of
      glyceraldehyde-3-phosphate dehydrogenase, the rise for BSA levels in pseudopodia
      vs migrated cells was comparable or greater than levels noted for established
      pseudopodial proteins, beta-actin and ezrin. The increase for dimerized BSA in
      pseudopodia compared to unmigrated cells was greater than the rise in levels of
      beta-actin, ezrin, HGF, and phosphorylated Met when pseudopodia were harvested
      from filters with 1 mum pores using either cell line. Fluorescein (F)-labeled BSA
      co-localized with HGF on actin-rich cellular protrusions and with CM-DiI labeled
      pseudopodial plasma membranes. The F-BSA highlighted small, individual
      pseudopodial profiles more so than complex pseudopodial networks (reticulopodia)
      or unmigrated cells. Labeled human serum albumin also decorated pseudopodia
      preferentially. Albumin's association with pseudopodia may help to explain its
      selective accumulation in astrocytomas in vivo. The leaky BBB permits serum
      albumin to enter the microenvironment of astrocytomas thus allowing their
      invasive cells contact with serum albumin as a source of fatty acids that would
      be useful for remodeling cell membranes in pseudopodia. Thus, albumin potentially
      aids and marks invasion as it accumulates in these tumors.

PMID- 16969372
TI  - Structural basis for macrolactonization by the pikromycin thioesterase.
AB  - Polyketides are a class of biologically active microbial and plant-derived
      metabolites that possess a high degree of structural and functional diversity and
      include many human therapeutics, among them anti-infective and anti-cancer drugs,
      growth promoters and anti-parasitic agents. The macrolide antibiotics,
      characterized by a glycoside-linked macrolactone, constitute an important class
      of polyketides, including erythromycin and the natural ketolide anti-infective
      agent pikromycin. Here we describe new mechanistic details of macrolactone ring
      formation catalyzed by the pikromycin polyketide synthase thioesterase domain
      from Streptomyces venezuelae. A pentaketide phosphonate mimic of the final
      pikromycin linear chain-elongation intermediate was synthesized and shown to be
      an active site affinity label. The crystal structures of the affinity-labeled
      enzyme and of a 12-membered-ring macrolactone product complex suggest a mechanism
      for cyclization in which a hydrophilic barrier in the enzyme and structural
      restraints of the substrate induce a curled conformation to direct macrolactone
      ring formation.

PMID- 16969373
TI  - Structural and mechanistic insights into polyketide macrolactonization from
      polyketide-based affinity labels.
AB  - Polyketides are a diverse class of natural products having important clinical
      properties, including antibiotic, immunosuppressive and anticancer activities.
      They are biosynthesized by polyketide synthases (PKSs), which are modular,
      multienzyme complexes that sequentially condense simple carboxylic acid
      derivatives. The final reaction in many PKSs involves thioesterase-catalyzed
      cyclization of linear chain elongation intermediates. As the substrate in PKSs is
      presented by a tethered acyl carrier protein, introduction of substrate by
      diffusion is problematic, and no substrate-bound type I PKS domain structure has
      been reported so far. We describe the chemical synthesis of polyketide-based
      affinity labels that covalently modify the active site serine of excised
      pikromycin thioesterase from Streptomyces venezuelae. Crystal structures reported
      here of the affinity label-pikromycin thioesterase adducts provide important
      mechanistic insights. These results suggest that affinity labels can be valuable
      tools for understanding the mechanisms of individual steps within multifunctional
      PKSs and for directing rational engineering of PKS domains for combinatorial
      biosynthesis.

PMID- 16969374
TI  - X-linked mental retardation: a comprehensive molecular screen of 47 candidate
      genes from a 7.4 Mb interval in Xp11.
AB  - About 30% of the mutations causing nonsyndromic X-linked mental retardation (MRX)
      are thought to be located in Xp11 and in the pericentromeric region, with a
      particular clustering of gene defects in a 7.4 Mb interval flanked by the genes
      ELK1 and ALAS2. To search for these mutations, 47 brain-expressed candidate genes
      located in this interval have been screened for mutations in up to 22 mental
      retardation (MR) families linked to this region. In total, we have identified 57
      sequence variants in exons and splice sites of 27 genes. Based on these data,
      four novel MR genes were identified, but most of the sequence variants observed
      during this study have not yet been described. The purpose of this article is to
      present a comprehensive overview of this work and its outcome. It describes all
      sequence variants detected in 548 exons and their flanking sequences, including
      disease-causing mutations as well as possibly relevant polymorphic and silent
      sequence changes. We show that many of the studied genes are unlikely to play a
      major role in MRX. This information will help to avoid duplication of efforts in
      the ongoing endeavor to unravel the molecular causes of MRX.

PMID- 16969375
TI  - Molecular genetic analysis of the human dihydrofolate reductase gene: relation
      with plasma total homocysteine, serum and red blood cell folate levels.
AB  - Disturbances in folate metabolism may increase the risk of certain malignancies,
      congenital defects and cardiovascular diseases. The gene dihydrofolate reductase
      (DHFR) is primarily involved in the reduction of dihydrofolate, generated during
      thymidylate synthesis, to tetrahydrofolate in order to maintain adequate amounts
      of folate for DNA synthesis and homocysteine remethylation. In order to reveal
      possible variation that may affect plasma total homocysteine (tHcy), serum folate
      and red blood cell (RBC) folate levels, we sequenced the DHFR coding region as
      well as the intron-exon boundaries and DHFR flanking regions from 20 Caucasian
      individuals. We identified a 9-bp repeat in the 5'-upstream region that partially
      overlapped with the 5'-untranslated region, and several single-nucleotide
      polymorphisms, all in non-coding regions. We screened subjects for the 9-bp
      repeat (n=417), as well as the recently reported 19-bp deletion in intron 1
      (n=330), and assessed their associations with plasma tHcy, serum and RBC folate
      levels. The 19-bp del/del genotype was associated with a lower plasma tHcy (
      14.4% [95% confidence interval: -23.5 to -4.5], P=0.006) compared with the wild
      type genotype. This may suggest that intracellular folate levels are affected.

PMID- 16969376
TI  - Sotos syndrome.
AB  - Sotos syndrome is an autosomal dominant condition characterised by a distinctive
      facial appearance, learning disability and overgrowth resulting in tall stature
      and macrocephaly. In 2002, Sotos syndrome was shown to be caused by mutations and
      deletions of NSD1, which encodes a histone methyltransferase implicated in
      chromatin regulation. More recently, the NSD1 mutational spectrum has been
      defined, the phenotype of Sotos syndrome clarified and diagnostic and management
      guidelines developed.

PMID- 16969377
TI  - Influence of germination and fermentation on bioaccessibility of zinc and iron
      from food grains.
AB  - OBJECTIVE AND DESIGN: Food grains such as green gram, chickpea and finger millet
      are often subjected to traditional processing involving germination and
      fermentation. This study was designed to assess the effect of germination of
      these grains on the bioaccessibility of zinc and iron. The effect of fermentation
      of a cereal-pulse combination as encountered in the preparation of breakfast
      dishes - idli, dosa and dhokla - on the same was also evaluated. Bioaccessibility
      measurement was made employing an in vitro simulated digestion method. RESULT:
      Zinc bioaccessibility was significantly decreased by germination (48 h) of finger
      millet (38%) and green gram (44%), while iron bioaccessibility was increased by
      62% (green gram), 39% (chickpea) and 20% (finger millet), concomitant with a
      reduction in tannin content. A fermented batter of rice+black gram - 2:1 (idli)
      and 3:1 (dosa) - had higher bioaccessibility values for zinc (71 and 50%,
      respectively), while iron bioaccessibility values were increased in these cases
      of fermentation to an even greater extent, namely 277 and 127%, respectively.
      Zinc and iron bioaccessibility was not improved by fermentation of the
      combination of chickpea, green gram, black gram and rice (1:1:0.5:0.5; dhokla). A
      fermentation of cereal-legume combinations of idli and dosa batter significantly
      reduced both phytate and tannin, while in the case of dhokla batter there was a
      continued significant presence of phytate associated with additional legumes -
      chickpea and green gram. CONCLUSION: Germination of food grains improved the
      bioaccessibility of iron but not that of zinc. Fermentation of a batter of cereal
      pulse combination in the preparation of idli and dosa enhanced the
      bioaccessibility of both zinc and iron, but not that of the combination used for
      the preparation of dhokla.

PMID- 16969378
TI  - Influence of three rapeseed oil-rich diets, fortified with alpha-linolenic acid,
      eicosapentaenoic acid or docosahexaenoic acid on the composition and
      oxidizability of low-density lipoproteins: results of a controlled study in
      healthy volunteers.
AB  - OBJECTIVE: To compare the individual effects of dietary alpha-linolenic acid
      (ALA), eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on low-density
      lipoprotein (LDL) fatty acid composition, ex vivo LDL oxidizability and
      tocopherol requirement. DESIGN, SETTING AND SUBJECTS: A randomized strictly
      controlled dietary study with three dietary groups and a parallel design,
      consisting of two consecutive periods. Sixty-one healthy young volunteers,
      students at a nearby college, were included. Forty-eight subjects (13 males, 35
      females) completed the study. INTERVENTIONS: Subjects received a 2-week wash-in
      diet rich in monounsaturated fatty acids (21% energy) followed by experimental
      diets enriched with about 1% of energy of ALA, EPA or DHA for 3 weeks. The omega
      3 (n-3) fatty acids were provided with special rapeseed oils and margarines. The
      wash-in diet and the experimental diets were identical, apart from the n-3 fatty
      acid composition and the tocopherol content, which was adjusted to the content of
      dienoic acid equivalents. RESULTS: Ex vivo oxidative susceptibility of LDL was
      highest after the DHA diet, indicated by a decrease in lag time (-16%, P<0.001)
      and an increase in the maximum amount of conjugated dienes (+7%, P<0.001). The
      EPA diet decreased the lag time (-16%, P<0.001) and the propagation rate (-12%,
      P<0.01). Tocopherol concentrations in LDL decreased in the ALA group (-13.5%,
      P<0.05) and DHA group (-7.3%, P<0.05). Plasma contents of tocopherol equivalents
      significantly decreased in all three experimental groups (ALA group: -5.0%, EPA
      group: -5.7%, DHA group: -12.8%). The content of the three n-3 polyunsaturated
      fatty acid differently increased in the LDL: on the ALA diet, the ALA content
      increased by 89% (P<0.001), on the EPA diet the EPA content increased by 809%
      (P<0.001) and on the DHA diet, the DHA content increased by 200% (P<0.001). In
      addition, the EPA content also enhanced (without dietary intake) in the ALA group
      (+35%, P<0.01) and in the DHA group (+284%, P<0.001). CONCLUSIONS: Dietary intake
      of ALA, EPA or DHA led to a significant enrichment of the respective fatty acid
      in the LDL particles, with dietary EPA preferentially incorporated. In the
      context of a monounsaturated fatty acid-rich diet, ALA enrichment did not enhance
      LDL oxidizability, whereas the effects of EPA and DHA on ex vivo LDL oxidation
      were inconsistent, possibly in part due to further changes in LDL fatty acid
      composition.

PMID- 16969379
TI  - Ratio of low serum zinc levels in elderly Japanese people living in the central
      part of Japan.
AB  - OBJECTIVE: Elderly patients often have impaired taste, nausea, anorexia and
      delayed healing of decubitus. In many of these patients, serum zinc levels are
      low and they respond to zinc supplementation. To date, no epidemics of zinc
      deficiency have been reported in Japan. We studied the prevalence of zinc
      deficiency and its causative factors in a typical local town in Japan. DESIGN:
      Cross-sectional study. SETTING: Nagano Prefecture (central Japan). SUBJECTS AND
      METHODS: Serum zinc levels were measured in 1009 habitants (18-96 years old) who
      participated in an annual mass health examination program of the City in 2003. Of
      all subjects, 86 with low serum zinc (<65 microg/dl) or high zinc (> or =90
      microg/dl) levels were randomly selected, and a dietary survey using 24-h
      recalling methods for 2 consecutive days was performed in 2004. Among them, blood
      was collected in the morning from 50 subjects (26-94 years old). RESULTS: The
      percentage of those with low serum zinc levels (2.5th percentile of Americans)
      was 37.9% in the elderly (> or =60 years old). The age-adjusted prevalence of low
      serum zinc was 21.1% in the aged population. A positive correlation was detected
      between zinc intake and serum zinc levels in elderly subjects (> or =60 years
      old). CONCLUSIONS: The possibility of zinc deficiency in adult inhabitants in
      central Japan rises with age. The deficiency correlates with dietary zinc intake.

PMID- 16969380
TI  - Relationship between a wide range of alcohol consumptions, components of the
      insulin-like growth factor system and adiponectin.
AB  - OBJECTIVE: To explore the relation between a wide range of alcohol consumptions
      and levels of the components of insulin-like growth factor system (IGFs) and
      adiponectin in humans. DESIGN: A cross-sectional study using controls from a case
      control study on ovarian and endometrial cancer. SETTINGS: The study included
      women hospitalized between 1999 and 2002 in Pordenone, Italy. SUBJECTS: One
      hundred and eight cancer-free (controls) with a median age of 61 years (range 29
      79 years), admitted for acute conditions unrelated to gynecologic, hormonal or
      metabolic disorders or diseases leading to dietary modifications. INTERVENTIONS:
      Levels of IGF-I (total and free), total IGF-II, IGF-binding protein 1 (IGFBP-1),
      IGFBP-3 and adiponectin were individually measured, and their distributions
      across strata of alcohol consumption were tested by the Kruskal-Wallis statistic.
      RESULTS: Median concentrations of total IGF-I were higher (P<0.01) in women
      reporting low (151 ng/ml) or no alcohol consumption (134 ng/ml) compared to
      drinkers of 12-23 g/day (103 ng/ml) or >or=24 g/day (118 ng/ml). Median
      concentrations were higher (P=0.05) for IGFBP-3 in non-drinkers (2333 ng/ml) and
      in light drinkers (2647 ng/ml) compared to drinkers of >or=24 g/day (2090 ng/ml).
      No statistically significant difference emerged for other IGFs across levels of
      alcohol intakes. Adiponectin was slightly lower for non-drinkers, compared to all
      drinkers categories. CONCLUSIONS: Our study suggests that alcohol consumption is
      related to circulating levels of components of the IGF system and adiponectin.
      These results may have a potential impact on the prevention of several chronic
      diseases. SPONSORSHIP: Italian Association for Research on Cancer, Milan, Italy,
      and Italian League against Tumours, Milan, Italy.

PMID- 16969381
TI  - Effects of hazelnut-enriched diet on plasma cholesterol and lipoprotein profiles
      in hypercholesterolemic adult men.
AB  - OBJECTIVE: Frequent consumption of nuts is associated with favorable plasma lipid
      profiles and reduced risk of coronary heart disease (CHD). This study was
      conducted to investigate the effects of hazelnut-enriched diet on plasma
      cholesterol and lipoprotein profiles in hypercholesterolemic adult men compared
      with baseline and control diet, and also to measure the anthropometric
      parameters, habitual physical activities, nutrient intake and endothelial
      function. SUBJECTS AND DESIGN: Fifteen hypercholesterolemic men aged 48+/-8 years
      were recruited voluntarily. A well-controlled, 2-period (P1 and P2) study design
      with a total of 8-week was implemented. In the P1, subjects consumed a control
      diet (low-fat, low-cholesterol and high-carbohydrate). During the P2, the control
      diet was supplemented with MUFA-rich hazelnut (40 g/day), which provided 11.6% of
      total energy content. Anthropometric parameters and habitual physical activities
      were recorded. Plasma total and HDL cholesterol, TAG, ApoA-1, Apo B, total
      homocysteine and glucose concentrations were measured. All parameters and
      measurements were obtained at baseline and end of each 4-week diet period.
      RESULTS: Body weights of subjects remained stable throughout the study. Compared
      with baseline, the hazelnut-enriched diet decreased (P<0.05) the concentrations
      of VLDL cholesterol, triacylglycerol, apolipoprotein B by 29.5, 31.8, and 9.2%,
      respectively, while increasing HDL cholesterol concentrations by 12.6%. Total/HDL
      cholesterol and LDL/HDL cholesterol ratios favorably decreased (P<0.05). Although
      insignificant there was a decreasing trend for the rest of parameters,
      particularly in total (5.2%) and LDL cholesterol (3.3%) in subjects consuming a
      hazelnut-enriched diet compared to that of the baseline. No changes were found in
      fasting levels of glucose, Apo A-1 and homocysteine between the control and
      hazelnut-enriched diets. CONCLUSIONS: This study demonstrated that a high-fat and
      high-MUFA-rich hazelnut diet was superior to a low-fat control diet because of
      favorable changes in plasma lipid profiles of hypercholesterolemic adult men and,
      thereby positively affecting the CHD risk profile. SPONSORSHIP: Funding provided
      by a grant from the Hazelnut Promotion Group, Giresun, Turkey.

PMID- 16969382
TI  - Reduction in oxidative stress by superoxide dismutase overexpression attenuates
      acute brain injury after subarachnoid hemorrhage via activation of Akt/glycogen
      synthase kinase-3beta survival signaling.
AB  - Recent studies have revealed that oxidative stress has detrimental effects in
      several models of neurodegenerative diseases, including subarachnoid hemorrhage
      (SAH). However, how oxidative stress affects acute brain injury after SAH remains
      unknown. We have previously reported that overexpression of copper/zinc
      superoxide dismutase (SOD1) reduces oxidative stress and subsequent neuronal
      injury after cerebral ischemia. In this study, we investigated the relationship
      between oxidative stress and acute brain injury after SAH using SOD1 transgenic
      (Tg) rats. SAH was produced by endovascular perforation in wild-type (Wt) and
      SOD1 Tg rats. Apoptotic cell death at 24 h, detected by a cell death assay, was
      significantly decreased in the cerebral cortex of the SOD1 Tg rats compared with
      the Wt rats. The mortality rate at 24 h was also significantly decreased in the
      SOD1 Tg rats. A hydroethidine study demonstrated that superoxide anion production
      after SAH was reduced in the cerebral cortex of the SOD1 Tg rats. Moreover,
      phosphorylation of Akt and glycogen synthase kinase-3beta (GSK3beta), which are
      survival signals in apoptotic cell death, was more enhanced in the cerebral
      cortex of the SOD1 Tg rats after SAH using Western blot analysis and
      immunohistochemistry. We conclude that reduction in oxidative stress by SOD1
      overexpression may attenuate acute brain injury after SAH via activation of
      Akt/GSK3beta survival signaling.

PMID- 16969383
TI  - When perfusion meets diffusion: in vivo measurement of water permeability in
      human brain.
AB  - Quantification of water permeability can improve the accuracy of perfusion
      measurements obtained with arterial spin labeling (ASL) methods, and may provide
      clinically relevant information regarding the functional status of the
      microvasculature. The amount of labeled water in the vascular and tissue
      compartments in an ASL experiment can be estimated based on their distinct
      diffusion characteristics, and in turn, water permeability determined from the
      relative vascular and tissue contributions. In the present study, a hybrid
      magnetic resonance imaging technique was introduced by marrying a continuous ASL
      method with a twice-refocused spin-echo diffusion sequence. Series of diffusion
      weighted ASL signals were acquired with systematically varied b values. The
      signals were modeled with fast and slow decaying components that were associated
      with the vascular and tissue compartments, respectively. The relative amount of
      labeled water in the tissue compartment increased from 61% to 74% and to 86% when
      the postlabeling delay time was increased from 0.8 to 1.2 and to 1.5 secs. With a
      b value of 50 secs/mm2, the capillary contribution (fast component) of the ASL
      signal could be effectively minimized. Using the single-pass approximation model,
      the water permeability of gray matter in the human brain was estimated based on
      the derived relative water fractions in the tissue and microvasculature. The
      potential for in vivo magnetic resonance mapping of water permeability was showed
      using two diffusion weighted ASL measurements with b=0 and 50 secs/mm2 in both
      healthy subjects and a case of brain tumor.

PMID- 16969385
TI  - IGF-I and IGFBP-3 augment transforming growth factor-beta actions in human renal
      carcinoma cells.
AB  - Renal cell carcinoma (RCC) is the most prevalent cancer of the kidney. In human
      RCC cells, we recently showed that insulin-like growth factor I (IGF-I) has
      growth-promoting effects regulated by IGF-binding protein 3 (IGFBP-3). In this
      study, the analysis was expanded to include the interaction between the IGF and
      transforming growth factor-beta (TGF-beta) systems in the human RCC cells Caki-2
      (from a primary tumor) and SK-RC-52 (from a metastasis). Functional effects such
      as cell proliferation, TGF-beta receptor (TbetaR) signaling, and IGFBP-3 levels
      were monitored after stimulation with various concentrations of IGF-I, TGF-beta,
      and IGFBP-3. In addition, human RCC tissues as well as experimental human RCC
      tumors were analyzed for cellular expression of phosphorylated Smad2 by
      immunohistochemistry. TGF-beta regulated the endogenous IGFBP-3 levels in these
      RCC cells as neutralizing anti-TGF-beta(1-3) antibodies strongly reduced the
      basal IGFBP-3 level. In addition, IGF-I increased the IGFBP-3 levels five- to
      eightfold with TGF-beta acting in synergy to enhance the IGFBP-3 levels 12- to 17
      fold. Neutralizing TGF-beta(1-3) activity circumvented the growth inhibitory
      effects of IGFBP-3 seen in SK-RC-52, whereas it inhibited the growth-promoting
      effects of IGFBP-3 in Caki-2. Moreover, IGF-I interacted directly with TGF-beta
      activation of the TbetaR complex by enhancing phosphorylation and nuclear
      translocation of Smad2. This study demonstrates a direct interaction of the IGF
      and TGF-beta systems in human renal carcinoma cells. The observations that IGF-I
      enhances the TGF-beta signaling and that TGF-beta promotes IGFBP-3 production and
      thus influence the biological activity of IGF may be of importance for future
      therapeutic options.

PMID- 16969384
TI  - Treatment of early mixed cellular and humoral renal allograft rejection with
      tacrolimus and mycophenolate mofetil.
AB  - This prospective study investigated the efficiency of the tacrolimus (Tac)
      combined with mycophenolate mofetil (MMF) alone without immunoadsorption (IA) or
      plasmapheresis (PPH) as treatment for early (within 2 weeks) acute humoral
      rejection (AHR) in non-sensitized renal allograft recipients. Of 160 patients
      enrolled in this prospective study, 11 patients had histologically and clinically
      confirmed early steroid-resistant acute rejection with an antibody response and
      received Tac-MMF therapy. No other aggressive rescue methods such as IA, PPH were
      used, according to the study design. Patients (n=11) were followed for 13.8+/-3.5
      months; nine were females. The complement-dependent cytotoxicity crossmatch was
      negative before transplantation in all patients and only positive for panel
      reactive antibody in one patient. Most of the rejection episodes were mixed with
      cellular rejection (four patients met Banff IIA criteria, five patients met Banff
      IIB, one patient met Banff IB, and one patient met Banff borderline). After
      16.19+/-6.16 days of treatment, all rejection episodes were successfully reversed
      and all graft functions were stable, with a mean serum creatinine level of 1.12+/
      0.32 mg/dl during follow-up. No patient suffered from severe infectious
      complications (except one case of urinary infection). Our investigation suggests
      that Tac combined with MMF alone is adequate to reverse early mixed cellular and
      humoral C4d-positive rejection in non-sensitized renal allograft recipients.

PMID- 16969386
TI  - The role of purinergic P2X7 receptors in the inflammation and fibrosis of
      unilateral ureteral obstruction in mice.
AB  - Receptors of the P2X7 type have been demonstrated in granulocytes,
      monocytes/macrophages, B and T lymphocytes, and have been involved in several
      cellular mechanisms including those related to inflammation and immunological
      response. This study attempted to investigate the role of these receptors on the
      inflammatory and fibrogenic response in the kidneys of unilateral ureteral
      obstruction (UUO), by using P2X7 knockout mice (-/-). C57Bl6 mice were submitted
      to left UUO and killed after 7 and 14 days. Histopathology using hematoxylin
      eosin, periodic-acid Schiff and Sirius-red staining, immunohistochemistry for
      macrophages, myofibroblasts, transforming growth factor-beta (TGF-beta)1 and
      P2X7, and immunofluorescence for apoptotic cells (terminal
      deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labeling)
      were performed. Protocols were as follows: (1) control; (2) sham; (3) control
      P2X7 (-/-); (4) sham P2X7 (-/-); (5) UUO wild type (WT); (6) UUO P2X7 (-/-).
      Myofibroblasts and Sirius-red staining were significantly lower in UUO P2X7 (-/-)
      mice at days 7 and 14, compared to UUO WT. Kidneys from UUO P2X7 (-/-) mice
      showed reduced number of inflammatory cells at day 14 but not at day 7, compared
      to UUO WT. TGF-beta1 was less in UUO P2X7 (-/-) mice at days 7 and 14 when
      compared to UUO WT. Macrophage infiltration and tubular apoptosis were lower in
      UUO P2X7 (-/-) at day 14 but not at day 7, compared to UUO WT. P2X7 was expressed
      only in tubular epithelial cells at day 7 of UUO WT mice. These findings
      constitute the first evidence that P2X7 receptors are implicated in macrophage
      infiltration, collagen deposition and apoptosis in response to ureteral
      obstruction in mice.

PMID- 16969387
TI  - Predicting initiation and progression of chronic kidney disease: Developing renal
      risk scores.
AB  - Epidemiological studies have raised awareness of the problem of undiagnosed
      chronic kidney disease (CKD) and suggest that early identification and treatment
      will reduce the global burden of patients requiring dialysis. This has
      highlighted the twin problems of how to identify subjects for screening and
      target intervention to those with CKD most likely to progress to end-stage renal
      disease. Prospective studies have identified risk factors for CKD in the general
      population as well as risk factors for progression in patients with established
      CKD. Risk factors may thus be divided into initiating factors and perpetuating
      factors, with some overlap between the groups. In this paper, we review current
      data regarding CKD risk factors and illustrate how each may impact upon the
      mechanisms underlying CKD progression to accelerate loss of renal function. We
      propose that these risk factors should be used as a basis for developing a renal
      risk score, analogous to the Framingham risk score for ischemic heart disease,
      which will allow accurate determination of renal risk in the general population
      and among CKD patients.

PMID- 16969388
TI  - Sleep disorders in end-stage renal disease: 'Markers of inadequate dialysis'?
AB  - Excessive daytime sleepiness and sleep disorders, including sleep apnea syndrome,
      restless legs syndrome, and periodic limb movement disorder, occur with increased
      frequency in patients with end-stage renal disease (ESRD). The detection and
      management of sleep disorders in ESRD patients is often challenging but may have
      significant clinical benefits. Some of the poor quality of life in ESRD may be
      attributed to the presence of concomitant sleep disorders, yet the classical
      symptoms of sleep disorders (poor concentration, daytime sleepiness, and
      insomnia) are often ascribed to the uremic syndrome itself. Conventional risk
      factors and screening tools used in the diagnosis of sleep disorders seem to have
      limited applicability in dialysis patients implicating the unique pathophysiology
      of sleep disorders in ESRD. Emerging evidence suggests that sleep apnea may
      contribute to the augmented cardiovascular event rates and to the accelerated
      development of atherosclerosis in ESRD. Whether treatment of sleep disorders in
      ESRD patients can affect the high morbidity and mortality of ESRD patients has
      yet to be elucidated. To date, conventional renal replacement therapies do not
      appear to have a significant impact on the treatment of sleep disorders in ESRD.
      The promising therapeutic effects of optimal uremia control in the forms of
      nocturnal hemodialysis and renal transplantation on sleep disorders require
      further mechanistic and clinical studies.

PMID- 16969389
TI  - Field-of-view shifted Shack-Hartmann wavefront sensor for daytime adaptive optics
      system.
AB  - For the daytime adaptive optics system, a field-of-view shifted Shack-Hartmann
      wavefront sensor (FSWFS), which is used to measure the aberrant wavefront under
      daytime conditions, is proposed. Because the field angle of the object signal in
      adaptive optics systems is much less than that of the sky background, the
      effective object signal is separated from the strong sky background. Experimental
      results indicate that FSWFS with a single focal-plane array can precisely and
      stably measure the aberrant wavefront information with a strong sky background
      under daytime conditions.

PMID- 16969390
TI  - Reverse orbiting of microparticles in optical vortices.
AB  - We report the observation of particles trapped at an air-water surface orbiting
      in a reverse direction with respect to the orbital angular momentum of the light
      field. The effect is explained by a combination of asymmetric particle shape and
      confinement of the particle on the 2D air-water interface. The experiment
      highlights the strong influence of the particle shape on the momentum transfer,
      an effect that is often not considered in optical trapping experiments.

PMID- 16969391
TI  - Linear relations of partially polarized and coherent electromagnetic fields.
AB  - We show that having a Wolf degree of coherence of unit modulus or having
      intrinsic degrees of coherence of unit modulus imply different relations between
      the electric fields of the light. The mean square meaning of such relations is
      discussed. On the one hand, we demonstrate that if the intrinsic degrees of
      coherence are equal to 1, then there is a linear relation between the electrical
      fields. On the other hand, we show that a Wolf degree of coherence of unit
      modulus corresponds to a stronger property that implies that the fields have to
      be proportional.

PMID- 16969392
TI  - Broadband dispersion-compensating photonic crystal fiber.
AB  - We present a modified dual-core photonic crystal fiber, based on pure silica,
      with special grapefruit holes in the inner cladding. The fiber has large,
      broadband negative dispersion, and the dispersion value varies linearly from -380
      t o-420 ps/(nm km) in the C band. To decrease the fabrication difficulty, large
      air holes are adopted. Furthermore, the chromatic dispersion of the fiber is not
      sensitive to the structure parameters. So the proposed fiber structure can
      greatly facilitate fiber drawing and can be used for broadband dispersion
      compensation.

PMID- 16969393
TI  - Core area scaling of Nd:Al-doped silica depressed clad hollow optical fiber and Q
      switched laser operation at 0.9 microm.
AB  - We demonstrate a Q-switched, cladding-pumped, Nd:Al-doped silica depressed clad
      hollow optical fiber (DCHOF) laser, which generated up to 133 microJ of pulse
      energy at a repetition rate of 5 kHz and 0.9 W of average output power at a high
      repetition rate (>20 kHz) in a diffraction-limited beam (M(2)=1.08) at 927 nm.
      The laser was tunable from 919 to 935 nm. This result shows the potential of the
      DCHOF structure for the suppression of unwanted long-wavelength radiation in
      large-area cores suitable for high-power Q-switched laser operation.

PMID- 16969394
TI  - Molecular modulation in a hollow fiber.
AB  - We report the extension of the technique of molecular modulation to a deuterium
      filled optical fiber. Using driving lasers at 807 and 1064 nm, each with a pulse
      energy of several millijoules and a 200 microm diameter fiber with a length of
      22.5 cm, we generate 12 sidebands with wavelengths spanning 1.56 microm to 254
      nm.

PMID- 16969395
TI  - Simultaneous measurement of bending and temperature based on a single sampled
      chirped fiber Bragg grating embedded on a flexible cantilever beam.
AB  - We propose and experimentally demonstrate a simple and practical scheme for
      simultaneous measurement of bending and temperature based on a single sampled
      chirped fiber Bragg grating with multiple resonant peaks, which is embedded on a
      flexible cantilever beam. The wavelength spacing of the grating can be changed by
      adjusting the bending curvature change, since the compressive strain gradient
      induced by the bending of the cantilever beam changes the chirp ratio of the
      fiber grating. However, the wavelength spacing of the fiber grating is not
      changed by the temperature variation; the multiple resonant wavelengths are only
      shifted into the longer wavelength because of the positive thermal-expansion and
      thermo-optic coefficients of the fiber grating. Consequently, the proposed scheme
      allows for discrimination between two effects of bending and temperature.

PMID- 16969396
TI  - Tunable Er3+-doped fiber amplifiers covering S and C+L bands over 1490-1610 nm
      based on discrete fundamental-mode cutoff filters.
AB  - We demonstrate thermo-optically tunable Er3+-doped fiber amplifiers covering S
      and C+L bands (1490-1610 nm) using fundamental-mode cutoff filters discretely
      located in a 17.5 m long standard Er3+-doped fiber. The material dispersion and
      waveguide structure of the tapered fibers are locally modified to produce high
      cutoff-efficiency filters that make the unwanted amplified spontaneous emission
      highly attenuated at the longer wavelengths, and the optical gain is thus moved
      toward the shorter wavelengths. The maximal signal gains are measured to be
      18.92, 37.18, and 15.19 dB with 980 nm pump power of 135 mW in the S, C, and L
      bands, respectively.

PMID- 16969397
TI  - Comment on "Reconstruction algorithm for high-numerical-aperture holograms with
      diffraction-limited resolution".
AB  - We comment on a recent Letter by Zhang et al. [Opt. Lett. 31, 1633 (2006)] in
      which the authors proposed a reconstruction algorithm for high-numerical-aperture
      (NA) holograms. Such an algorithm has been available for in-line holography for
      more than a decade. The authors' "achievement" of high NA for digital in-line
      holography, NA=0.17, is below what was reported already several years ago
      (NA=0.30) and is considerably lower than what is routinely achieved now. We
      present reconstructions of holograms acquired with NAs above 0.4 in which we show
      maximal achievable resolution.

PMID- 16969399
TI  - Electroholographic tunable volume grating in the g44 configuration.
AB  - The g(44) grating is an electroholographic transmission grating in which the
      applied field is perpendicular to both the grating vector and the wave vector of
      the incident beam. It is argued that in this configuration the incident beam
      traverses through a periodically rotating index ellipsoid. It is shown that in
      the g(44) configuration the Bragg condition is fulfilled for a specific value of
      the applied field and for a diffracting beam polarization that is perpendicular
      to that of the incident beam. Consequently, the g(44) grating can be used as an
      electrically controlled filter. Tunability of 7 nm is demonstrated in a 2mm thick
      grating.

PMID- 16969400
TI  - Convertible two-dimensional-three-dimensional display using an LED array based on
      modified integral imaging.
AB  - We propose a two-dimensional (2D) to three-dimensional (3D) convertible display
      technique using a light-emitting diode (LED) array based on the principle of
      modified integral imaging. This system can be electrically converted between 3D
      and 2D modes by using different combinations of LEDs in the LED array without any
      mechanical movement. The LED array, which is controlled electrically, is used for
      backlight, and a lens array is used for making a point light source array with
      higher density. We explain the principle of operation and present experimental
      results.

PMID- 16969401
TI  - Resolution of 90 nm (lambda/5) in an optical transmission microscope with an
      annular condenser.
AB  - Resolution of 90 nm was achieved with a research microscope simply by replacing
      the standard bright-field condenser with a homebuilt illumination system with a
      cardioid annular condenser. Diffraction gratings with 100 nm width lines as well
      as less than 100 nm size features of different-shaped objects were clearly
      visible on a calibrated microscope test slide. The resolution increase results
      from a known narrower diffraction pattern in coherent illumination for the
      annular aperture compared with the circular aperture. This explanation is
      supported by an excellent accord of calculated and measured diffraction patterns
      for a 50 nm radius disk.

PMID- 16969402
TI  - Error analysis for rotating active Stokes-Mueller imaging polarimeters.
AB  - Retrieval of Mueller matrices from intensity measurements is a noise-sensitive
      process. In addition, the choice of the method used for extracting Mueller matrix
      elements greatly influences the precision of the final results. Among available
      procedures, three have been tested and their robustness analyzed by adding
      Gaussian noise to computer synthesized data and have been verified by comparing
      experimental data. As expected, the methods based on classical matrix inversion
      reach their noise reduction limit even if more data are considered. In contrast,
      the discrete Fourier transform approach features a remarkable stability. The
      identified reason is that the retrieval process corresponds to filtering with a
      periodic kernel.

PMID- 16969403
TI  - High-resolution beam steering using microlens arrays.
AB  - Imaging or beam-steering systems employing a periodic array of microlenses or
      micromirrors suffer from diffraction problems resulting from the destructive
      interference of the beam segments produced by the array. Simple formulas are
      derived for beam steering with segmented apertures that do not suffer from
      diffraction problems because of the introduction of a moving linear phase shifter
      such as a prescan lens before the periodic structure. The technique substantially
      increases the resolution of imaging systems that employ microlens arrays or
      micromirror arrays. Theoretical, numerical, and experimental results
      demonstrating the high-resolution imaging concept using microlens arrays are
      presented.

PMID- 16969404
TI  - Mode-locked ring lasers for the backscattering measurement of mirrors.
AB  - A new method for measuring the backscattering produced by mirrors is presented. A
      mode-locked ring laser allows us to achieve more sensitivity than with any other
      technique. The present sensitivity to a minimum intensity backscattering
      coefficient (ratio of backscattered versus incident intensity) of 10(-15) can be
      enhanced through stabilization. We compare results realized with this technique
      with results issued from classical bidirectional reflectance distribution
      function measurements.

PMID- 16969405
TI  - Two-photon-excited fluorescence from silicate glass containing tantalum ions
      pumped by a near-infrared femtosecond pulsed laser.
AB  - We report a novel phenomenon in sodium-calcium-silicate glass doped with Ta(5+).
      Under irradiation with a 780 nm femtosecond pulsed laser, strong blue emission
      centered at about 420 nm could be observed. The spectral characteristics are
      similar to those pumped by ultraviolet photons. The log-log correlation between
      integrated emission intensity and pump power reveals that a two-photon absorption
      process is involved in the phenomenon. It is suggested that the presence of
      localized Ta(5+)5d(0) energy levels is responsible for the appearance of the blue
      emission. The results indicate that transition metal ions without d electrons
      play an important role in fields of optics when embedded into glass hosts.

PMID- 16969406
TI  - Ultralow-jitter and -amplitude-noise semiconductor-based actively mode-locked
      laser.
AB  - We report a semiconductor-based, low-noise, 10.24 GHz actively mode-locked laser
      with 4.65 fs of relative timing jitter and a 0.0365% amplitude fluctuation (1 Hz
      to 100 MHz) of the optical pulse train. The keys to obtaining this result were
      the laser's high optical power and the low phase noise of the rf source used to
      mode lock the laser. The low phase noise of the rf source not only improves the
      absolute and relative timing jitter of the laser, but also prevents coupling of
      the rf source phase noise to the pulse amplitude fluctuations by the mode-locked
      laser.

PMID- 16969407
TI  - Dynamics of cell membranes and the underlying cytoskeletons observed by
      noninterferometric widefield optical profilometry and fluorescence microscopy.
AB  - Combining the noninterferometric wide-field optical profilometry technique with
      fluorescence microscopy, we observe the membrane activities of a living cell as
      well as the structures of its cytoskeletons. The membrane ripples of a
      lamellipodium are related to similar structures of the underlying actin
      filaments. However, we find the ripples appear prior to and disappear later than
      the corresponding actin filament structures, which supports the elastic Brownian
      ratchet model of cell motility. In addition, we measure the three-dimensional
      movement of a fibronectin-coated latex bead on the membrane. The bead motion is
      determined by the movement and branching of the actin molecules on the filament,
      as well as by the displacement of the filament itself.

PMID- 16969408
TI  - Endoscopic, rapid near-infrared optical tomography.
AB  - This is believed to be the first demonstration of near-infrared (NIR) optical
      tomography employed at the endoscope scale and at a rapid sampling speed that
      allows translation to in vivo use. A spread-spectral-encoding technique based on
      a broadband light source and linear-to-circular fiber bundling was used to
      provide endoscopic probing of many source-detector fibers for tomography as well
      as parallel sampling of all source-detector pairs for rapid imaging. Endoscopic
      NIR tomography at an 8 Hz frame rate was achieved in phantoms and tissue
      specimens with a 12 mm probe housing eight sources and eight detectors. This
      novel approach provides the key feasibility studies to allow this blood-based
      contrast imaging technology to be attempted in detection of cancer in internal
      organs via endoscopic interrogation.

PMID- 16969409
TI  - In vivo assessment of human skin aging by multiphoton laser scanning tomography.
AB  - Changes of dermal collagen and elastin content are characteristic for skin aging
      as well as for pathological skin conditions. To evaluate these changes, we used
      in vivo multiphoton laser tomography to measure two-photon excited
      autofluorescence (AF) and second harmonic generation (SHG). We tested 18 patients
      of all ages and calculated the SHG-to-AF aging index of dermis (SAAID). We
      observed a negative relationship between the SAAID and age, which was accelerated
      for the female (n=7) subgroup. The current findings are the first in vivo
      demonstration of this relationship, and they show that specific characteristics
      of aged skin such as the ratio of extracellular matrix components collagen and
      elastin can be evaluated by in vivo AF and SHG measurements using near-IR
      femtosecond laser pulses.

PMID- 16969411
TI  - High-power third-harmonic flat pulse laser generation.
AB  - The generation of a high-power laser pulse at 266 nm that is longitudinally
      shaped according to a prefixed intensity profile is reported. The main features
      of the pulse shape modifications due to second- and third-harmonic conversions
      are measured, and the results are in good agreement with the theory. The UV
      temporal shape depends on the chirp of the fundamental pulse and on the crystal
      phase-matching angle. Exploiting the large stretching imposed on the third
      harmonic signal, we show that the pulse intensity profile can be obtained by
      spectral single-shot measurements.

PMID- 16969410
TI  - Linear optical coherence tomography system with extended measurement range.
AB  - Optical coherence tomography (OCT) sensors traditionally use scanning optical
      delay lines with moving parts and a single detector. OCT systems with a linear
      detector array (linear OCT or L-OCT) are simple and robust, but a detector with
      approximately 10,000 pixels is needed for an imaging depth of 2mm, which is
      necessary for most biomedical applications. We present a new optical setup for L
      OCT with an increased measurement range. An additional grating performs a
      reduction of the spatial frequencies of the fringe pattern on the detector
      without loss in the signal-to-noise ratio, so the signal can be sampled with a
      minimal number of pixels. The theory for this approach is addressed and the first
      measurements are presented.

PMID- 16969412
TI  - Lattice solitons in self-defocusing optical media: analytical solutions of the
      nonlinear Kronig-Penney model.
AB  - A novel method for obtaining analytical solitary wave solutions of the nonlinear
      Kronig-Penney model in periodic photonic structures with self-defocusing
      nonlinearity is applied for providing generic families of solutions corresponding
      to the gaps of the linear band structure. Characteristic cases are shown to be
      quite robust under propagation.

PMID- 16969413
TI  - Pushing the hyperpolarizability to the limit.
AB  - We use numerical optimization to find a one-dimensional potential energy function
      that yields the largest hyperpolarizability, which we find is within 30% of the
      fundamental limit. Our results reveal insights into the character of the
      potential energy functions and wave functions that lead to the largest
      hyperpolarizability. We suggest that donor-acceptor molecules with a conjugated
      bridge with many sites of reduced conjugation to impart conjugation modulation
      may be the best paradigm for making materials with huge hyperpolarizabilities
      that approach the fundamental limit.

PMID- 16969414
TI  - Quasi-phase-matched generation of optical intensity waves.
AB  - The evolution of modulated light in a nonlinear medium, when described in terms
      of intensity waves, depends critically on a phase-matching condition for the
      intensity waves. We formally develop the conditions for quasi-phase matching of
      the interacting intensity waves and show that a periodic nonlinearity can be
      utilized to eliminate the dephasing between them. This is verified using
      stimulated Brillouin scattering with a periodically nonlinear optical fiber that
      has a period length equal to one-half of the (modulation) wavelength of the
      intensity waves.

PMID- 16969415
TI  - Strong-field molecular ionization: determination of ionization probabilities
      calibrated with field-free alignment.
AB  - We report an original optical method providing the probability of molecular
      ionization induced by femtosecond laser pulses. The approach consists of
      exploiting molecular alignment to extract reliable information about ionization.
      The cross defocusing technique implemented for this purpose reveals a sensitivity
      with respect to postpulse alignment, as well as to the free electron density
      induced by the ultrashort laser pulse. The analysis of the resulting signal thus
      gives access to absolute single-ionization probabilities calibrated through the
      degree of alignment, provided that free electrons are produced mainly by single
      ionization. The relevance of the method is assessed in N2.

PMID- 16969416
TI  - Transverse and soliton instabilities due to counterpropagation through a
      reflection grating in Kerr media.
AB  - Transverse instabilities are shown to accompany counterpropagation of optical
      beams through reflection gratings in Kerr media. The instability threshold of
      continuous waves is analytically derived, and it is shown that the presence of
      the grating broadens and narrows the stability region of plane waves in focusing
      and defocusing media, respectively. Furthermore, counterpropagating soliton
      stability is numerically investigated and compared with the transverse modulation
      instability analysis, revealing an underlying physical link.

PMID- 16969417
TI  - Nanofabrication of a space-variant optical transmission filter.
AB  - A space-variant optical transmission filter is demonstrated for which a
      simplified process is used to tailor the spatial response of the filter across
      the surface of a single wafer. A multilayer stack, of alternating high or low
      refractive index dielectric materials, was used to produce a narrow transmission
      notch in the center of a wide stop band. Subsequent patterning and etching of
      arrays of holes through the volume of the dielectric stack was performed to
      control the fill factor of the dielectric in the layers. The position of the
      transmission notch within the reflection spectrum was varied across the device
      surface by adjusting the hole diameter of the hole arrays. Experimental and
      numerical simulation were used to confirm the space-variant transmission
      characteristics of a single-wafer sample with two zones of different hole
      diameter arrays in the 1550 nm wavelength regime.

PMID- 16969418
TI  - Analog low-loss full-range phase modulation by utilizing a V-shaped switched
      ferroelectric liquid-crystal cell in reflective mode.
AB  - We have studied the analog (V-shaped switching) mode in ferroelectric liquid
      crystals in reflective mode for analog phase modulation applications. We have
      found that several combinations of cell thicknesses and input polarization states
      exist for which near-lossless analog phase modulation with a range of
      approximately 2pi rad is obtained, and we demonstrate one such combination
      experimentally. Despite a slight deviation from the ideal conditions, e.g., the
      tilt angle was 38 degrees instead of the desired 45 degrees , virtually pure
      1.6pi rad phase modulation was obtained; the measured values agree very well with
      our numerical simulations of the real device.

PMID- 16969419
TI  - Nonresonant cascaded acousto-optic mode coupling.
AB  - Nonresonant cascaded acousto-optic mode coupling under an overall phase-matching
      condition is presented, where phase matching is not satisfied for each of the
      coupling stages but the sum of the two acoustic momenta matches the optical phase
      detuning between the source mode and the destination mode. As a special
      nonresonant cascaded case, conversion from LP(01) to LP(21) and LP(02) driven by
      a single acoustic frequency is predicted theoretically and demonstrated
      experimentally.

PMID- 16969420
TI  - Generalized Helmholtz-Gauss beam and its transformation by paraxial optical
      systems.
AB  - We introduce the generalized Helmholtz-Gauss (gHzG) beam and analyze its
      propagation through optical systems described by ABCD matrices with real and
      complex elements. The transverse mathematical structure of the gHzG beam is form
      invariant under paraxial transformations and reduces to those of ordinary HzG and
      modified HzG beams as special cases. We derive a closed-form expression for the
      fractional Fourier transform of gHzG beams.

PMID- 16969421
TI  - Suggestion for qualitative lidar identification of different types of aerosol
      using the two-wavelength rotational Raman and elastic lidar.
AB  - Aerosols are important parameters in the meteorological and environmental fields,
      and remote aerosol identification is extremely desirable. We have proposed and
      designed a two-wavelength (355 and 532 nm) rotational Raman and elastic lidar
      that can measure the wavelength dependence of the aerosol backscattering
      coefficient without any assumptions about the Angstrom coefficient or the
      overlapping function from low (100 m) to high (10 km) altitude, depending on the
      weather conditions. We have measured the differences in the backscattering ratios
      (BRs) among a cloud, aerosol in the boundary layer, and Asian dust. The ratio of
      the aerosol backscattering coefficients between two wavelengths is a fingerprint
      of an aerosol, which is similar to the Angstrom coefficient. The BR value for a
      typical aerosol ranged from 0.56 to 0.4 in the boundary layer and from 0.5 to 0.1
      for Asian dust. The BR value of water droplet was not unique but was spread over
      a wide range because of its size distributions.

PMID- 16969422
TI  - Passively correcting phase drift in two-dimensional infrared spectroscopy.
AB  - Heterodyned two-dimensional (2D) IR spectra often suffer from inaccurate pulse
      delays and phase drift. We report a passive method of correcting these two
      inaccuracies by using wedged optics for subfemtosecond pulse delay resolution and
      reference measurements for phase corrections. Our approach is easy to implement
      into existing 2D IR spectrometers and makes experiments requiring long-term phase
      stability possible, such as the collection of 3D IR spectra.

PMID- 16969423
TI  - Fast light in fully coherent gain media.
AB  - We analyze the propagation of fast-light pulses through a finite-length resonant
      gain medium both analytically and numerically. We find that intrinsic
      instabilities can be avoided in attaining a substantial peak advance with an
      ultrashort rather than a long or adiabatic probe.

PMID- 16969424
TI  - Pulse-amplitude equalization by negative impulse modulation for rational harmonic
      mode locking.
AB  - We propose a novel technique based on negative impulse modulation for pulse
      repetition rate multiplication by rational harmonic mode locking with pulse
      amplitude-equalized pulses directly from the laser cavity. We have generated a
      pulse train of 15 GHz with more than 16 dB suppression of unwanted amplitude
      modulation spurs by using a 1 GHz RF signal. This is the highest suppression
      ratio for a repetition rate multiplication factor of 15 to our knowledge.

PMID- 16969425
TI  - Simultaneous visualization of spatial and chromatic aberrations by two
      dimensional Fourier transform spectral interferometry.
AB  - We demonstrate the use of a simple tool to simultaneously visualize and
      characterize chromatic and spherical aberrations that are present in multiphoton
      microscopy. Using two-dimensional Fourier transform spectral interferometry, we
      measured these aberrations, deducing in a single shot spatiotemporal effects in
      high-numerical-aperture objectives.

PMID- 16969426
TI  - Modelling RNA folding under mechanical tension.
AB  - We investigate the thermodynamics and kinetics of RNA unfolding and refolding
      under mechanical tension. The hierarchical nature of RNA structure and the
      existence of thermodynamic parameters for base pair formation based on nearest
      neighbour interactions allows modelling of sequence-dependent folding dynamics
      for any secondary structure. We calculate experimental observables such as the
      transition force for unfolding, the end-to-end distribution function and its
      variance, as well as kinetic information, for a representative RNA sequence and
      for a sequence containing two homopolymer segments: A.U and G.C.

PMID- 16969427
TI  - Combined cannabinoid therapy via an oromucosal spray.
AB  - Extensive basic science research has identified the potential therapeutic
      benefits of active compounds extracted from the Cannabis sativa L. plant (the
      cannabinoids). It is recognized that a significant proportion of patients
      suffering with the debilitating symptoms of pain and spasticity in multiple
      sclerosis or other conditions smoke cannabis despite the legal implications and
      stigma associated with this controlled substance. GW Pharmaceuticals have
      developed Sativex (GW- 1,000-02), a combined cannabinoid medicine that delivers
      and maintains therapeutic levels of two principal cannabinoids, delta-9
      tetrahydrocannabinol (THC) and cannabidiol (CBD), via an oromucosal pump spray,
      that aims to minimize psychotropic side effects. Sativex has proved to be well
      tolerated and successfully self-administered and self-titrated in both healthy
      volunteers and patient cohorts. Clinical assessment of this combined cannabinoid
      medicine has demonstrated efficacy in patients with intractable pain (chronic
      neuropathic pain, pain due to brachial plexus nerve injury, allodynic peripheral
      neuropathic pain and advanced cancer pain), rheumatoid arthritis and multiple
      sclerosis (bladder problems, spasticity and central pain), with no significant
      intoxication-like symptoms, tolerance or withdrawal syndrome.

PMID- 16969428
TI  - Insulin detemir: a review.
AB  - Patients with diabetes are at increased risk of mortality and morbidity from
      micro- and macrovascular complications (1, 2). Landmark studies in type 1 and 2
      diabetes have clearly shown that improved glycemic control leads to better
      outcomes (3-6). With the introduction of the General Medical Service contract,
      the England and Wales National Service Framework, and other schemes, there is a
      national drive to improve control in patients with diabetes. The treatment of
      diabetes was revolutionized shortly after the turn of the 20th century by the
      extraction and purification of insulin. Since methods to protract (i.e., prolong)
      the action of insulin were developed in the 1930s, little changed in this
      technology until the turn of this century. At this time there was renewed
      interest in the importance of basal insulin in controlling diabetes and thus
      preventing or delaying complications, and so technology advanced again. Two new
      basal insulin analogues have come to the market: insulin glargine, which has been
      widely used for some years now, and detemir. This review describes the novel
      method of protraction employed by insulin detemir, discusses the possible
      therapeutic benefits of this method of protraction, and describes the findings of
      studies comparing insulin detemir with other currently available basal insulin
      preparations. It is not the intention of this paper to be a review of all the
      currently available long-acting insulin analogues.

PMID- 16969429
TI  - Vildagliptin: a novel DPP-4 inhibitor with pancreatic islet enhancement activity
      for treatment of patients with type 2 diabetes.
AB  - Type 2 diabetes is now one of the most challenging health-care problems, and
      novel treatment strategies are required. The pancreatic islet dysfunction of type
      2 diabetes involves problems with both insulin and glucagon since appropriate
      levels of both hormones are required for maintenance of glucose homeostasis.
      Enhancement of pancreatic function by incretins such as glucagon-like peptide
      (GLP)-1 is a new therapeutic approach. These incretins are inactivated by the
      enzyme dipeptidyl peptidase (DPP)-4. Vildagliptin is a potent, orally active,
      highly selective DPP-4 inhibitor that enhances the antidiabetic actions of the
      incretins. Pharmacokinetic studies showed that it is absorbed rapidly but has a
      sufficiently long period of action to require only once-daily dosing. Three phase
      II studies of vildagliptin use for 12 weeks in patients with type 2 diabetes have
      been reported. When vildagliptin was used either as monotherapy or combined with
      metformin, the treatment versus placebo resulted in significant reductions in
      hemoglobin (Hb)A(1c). The HbA(1c) was maintained during extended treatment over
      one year in the study of combination use with metformin. The studies indicated
      that the greater glycemic control appears to reflect an improvement in islet
      function. The improvement in glycemic control with vildagliptin was not
      associated with any body weight gain. Vildagliptin did not cause any clinically
      relevant changes in safety and was well tolerated. Therefore, further studies are
      being carried out on vildagliptin to assess long-term efficacy and safety in
      patients with type 2 diabetes.

PMID- 16969430
TI  - Anidulafungin: a new echinocandin for the treatment of fungal infections.
AB  - Immunocompromised hosts are at increased risk for invasive fungal infections.
      Over the last five decades, the mainstay of therapy against systemic mycoses has
      revolved around amphotericin B deoxycholate. Unfortunately, this drug has
      substantial toxicities, and agents such as fluconazole were developed as an
      alternative to treat and prevent these invasive infections. Due to widespread
      use, fluconazole-resistant organisms have emerged; therefore, new agents with
      improved safety, efficacy and tolerability have now become desirable. The
      echinocandins are a new class of antifungal agents with novel activity against
      the fungal cell wall. In February 2006, the U.S. Food and Drug Administration
      approved the echinocandin anidulafungin for the treatment of patients with
      candidemia, peritonitis, intra-abdominal abscesses and esophageal candidiasis.

PMID- 16969431
TI  - Treatment of acute retinal necrosis syndrome.
AB  - Acute retinal necrosis is a distinct ocular viral syndrome with a potentially
      devastating visual outcome, traditionally treated with intravenous acyclovir
      followed by oral acyclovir. The goals of therapy include accelerating the
      resolution of the infection in the affected eye and prevention of contralateral
      involvement. Recently, several small case series and case reports have described
      the use of newer oral antivirals such as valacyclovir, famciclovir or
      valganciclovir, alone or in combination with adjunctive intravitreal foscarnet or
      ganciclovir injections for the treatment of acute retinal necrosis (1-4). The
      purpose of this article is to describe various therapies available to
      practitioners who may treat patients with acute retinal necrosis.

PMID- 16969432
TI  - Postnatal depression in Australian general practice.
AB  - The BEACH program, a continuous national study of general practice activity in
      Australia, gives us an overview of encounters at which postnatal depression was
      managed. This provides a backdrop against which the articles in this issue of
      Australian Family Physician can be further considered.

PMID- 16969433
TI  - Perinatal depression--assessment and management.
AB  - BACKGROUND: Depression and anxiety often begin in pregnancy, particularly third
      trimester, therefore 'perinatal' rather than postnatal depression might be a
      better term to describe this disorder. OBJECTIVE: This article outlines an
      approach to assessment and management of perinatal depression. DISCUSSION:
      Psychological difficulties are common after childbirth and have potentially
      serious consequences. Treatment needs to consider the complex interplay of
      biology and psychology, and both mother and infant need consideration. Early,
      assertive identification and sensitive management, mindful of risks and benefits
      to both mother and infant, is the best current approach to improving outcomes.

PMID- 16969434
TI  - The postpartum visit--why wait 6 weeks?
AB  - BACKGROUND: In many western countries, the traditional 6 week check is a routine
      medical review of a mother and her baby 6 weeks after the birth. In Australia,
      general practitioners perform the majority of postpartum assessments. OBJECTIVE:
      This article discusses some of the common issues that concern women following the
      birth of a baby, and the medical conditions GPs need to address in the postpartum
      period. DISCUSSION: The research literature does not support any benefit of a 6
      week check. However, clinical evidence, our expertise as GPs, and our personal
      experiences, clearly indicate that the postpartum period is a time of tremendous
      change, increased health problems, and emotional upheaval for new parents.
      General practitioners are in an ideal position to assist families during this
      period and may consider a sooner rather than later, proactive rather than
      reactive, approach to postpartum care.

PMID- 16969435
TI  - The crying baby.
AB  - BACKGROUND: Up to 20% of parents report a problem with their infant crying in the
      first 3 months of life. The majority of babies have no organic cause of crying
      and most crying subsides by 3-4 months. OBJECTIVE: This article describes the
      management of persistent crying in the first 3 months of life. DISCUSSION:
      Management includes exclusion of medical causes and ensuring the baby is
      adequately rested and fed. Unexplained episodes of crying can be managed by:
      carrying the baby, going for a walk with baby in the pram, giving baby a deep,
      warm bath, or playing white noise or environmental sounds to distract the baby
      from crying. Postnatal depression is common in mothers of crying babies and
      should be actively screened for and appropriate clinical help offered if
      required. All families benefit from support including a review appointment and
      practical help around the home where possible.

PMID- 16969436
TI  - Breastfeeding--managing 'supply' difficulties.
AB  - BACKGROUND: Many breastfeeding women have concerns about their milk supply; 'not
      enough milk' is the most common reason women give for stopping breastfeeding,
      however their concern is often unwarranted. OBJECTIVE: The article describes the
      process of history taking and examination of mother and infant to determine if
      the mother's milk supply is adequate, the causes of insufficient milk supply, and
      possible investigations and management. DISCUSSION: Insufficient milk supply may
      be secondary to maternal conditions such as postpartum haemorrhage or breast
      reduction surgery, or infant factors such as tongue-tie or ill health. In many
      cases, milk supply can be increased by frequent, regular milk removal. Medication
      to increase milk supply (galactogogues) such as domperidone, may also play a
      role. General practitioners can provide reassurance if milk supply is adequate,
      or can assist in resolving the problem if milk supply is low.

PMID- 16969437
TI  - What about dad? Psychosocial and mental health issues for new fathers.
AB  - BACKGROUND: Although motherhood and the mother-infant bond have been extensively
      researched, the same is not true for fatherhood and the father-infant bond.
      OBJECTIVE: This article discusses the psychological tasks of the expectant
      father, the adjustment issues for men during their partners pregnancy and the
      postnatal period, and the development of the father-infant bond. DISCUSSION: The
      9 months of pregnancy are conceptualised as a time of psychological preparation
      for the first time expectant father. Four psychological tasks of this period are
      described with guidelines regarding how a health professional might assess and
      foster progress. In the postnatal period, 10% of new fathers will have a partner
      suffering from postnatal depression and the male response to this can positively
      or negatively influence recovery. This article concludes that the father-infant
      relationship is influenced by the partner relationship as well as the fathers
      psychological wellbeing.

PMID- 16969438
TI  - Complementary medicine for pregnancy complications.
AB  - For some women, pregnancy can bring a myriad of distressing symptoms. Nausea
      affects up to 85% of women during early pregnancy and about half of these women
      also experience vomiting. For some women, it can be very debilitating.
      Conventional anti-emetics bring with them a risk of potential teratogenic effects
      during the critical stage of early pregnancy. Women tend to feel more comfortable
      taking a natural or herbal substance to help manage these issues.

PMID- 16969439
TI  - Self induction of abortion with instrumentation.
AB  - In underdeveloped countries, where abortion is still illegal and not easily
      accessible, the number of unsafe abortions is soaring, as are the associated
      complications. However, in developed countries, where termination of pregnancy is
      legal and freely accessible, unsafe methods are uncommonly seen and reported. We
      report one such case of self induced abortion with instrumentation that presented
      to an accident and emergency department in the United Kingdom.

PMID- 16969440
TI  - The abortion debate in Australia.
AB  - I recently watched a fascinating documentary about the crusade of Dr Bertram
      Wainer in the 1960s to bring the practice of illegal abortion in Victoria to an
      end. It documented the profound horror of the backyard abortion that so often
      ended in infection, sterility or death, and served as a potent reminder of a
      practice to which we must never return. Of course that cant happen again,
      abortion is legal now, isnt it? In Victoria in 1969 a Supreme Court judge ruled
      that an abortion is not unlawful if a doctor believed that: the abortion is
      necessary to preserve the woman from serious danger to her life or physical or
      mental health (Menhennit ruling). In Australia today however, abortion law
      remains conditional, unclear and inconsistent and, except in the ACT, is still
      part of criminal statutes.

PMID- 16969441
TI  - Gestational diabetes--worth finding and actively treating.
AB  - Gestational diabetes affects around 5% of pregnant women, however the value of
      screening women for gestational diabetes has been hotly debated. On the positive
      side there has been potential benefits for the baby and, on the negative side,
      the costs of managing gestational diabetes to the mother. This controversy has
      largely been settled with the publication of the Australasian Carbohydrate
      Intolerance Study (ACHOIS). This article reviews the implications of ACHOIS for
      Australian women and their general practitioners.

PMID- 16969442
TI  - Managing acne vulgaris effectively.
AB  - The management of acne is a gratifying experience. Available treatments are
      effective, relatively nontoxic and generally safe. However, there is no quick
      fix. Antibiotics, hormone therapies and topical therapies are maintenance
      treatments. Isotretinoin can induce remission, as can some of the newer physical
      modalities of lights, lasers and radiofrequency devices. Effective management of
      acne often requires using a combination of treatments that act on different parts
      of the pathogenic process of acne development.

PMID- 16969443
TI  - Sleep disturbances in the disabled child--a case report and literature review.
AB  - Sleep disturbances in children are common. In children with intellectual
      disabilities sleeping problems are more common. This may result in increased
      burden of illness, additional parental stress, and day time behavioural
      difficulties. This article illustrates the problems that sleep disturbances
      create for children with disabilities and discusses methods for managing sleep
      problems.

PMID- 16969444
TI  - Skin cancer in patients with multiple health problems.

PMID- 16969445
TI  - Stem cells--a clinical update.
AB  - BACKGROUND: Stem cells of adult origin have been used clinically for 40 years in
      the treatment of haematological neoplasms such as leukaemia. These cells were
      originally obtained from bone marrow, but are now also being derived from
      umbilical cord blood. OBJECTIVE: With the increasing public awareness of stem
      cell use, general practitioners need to be aware for which disorders these cells
      can, and are, being used. DISCUSSION: Recent clinical trials with stem cells have
      been for ischaemic heart disease and to assist nonunion of bone. Other adult stem
      cells used in clinical trials include olfactory cells for spinal cord lesions,
      and human fetal pancreatic cells for type 1 diabetes. Adult stem cells, however,
      have limited potential to differentiate into different cell types. Human
      embryonic stem cells can be converted into cells of all lineages. They first
      became available for research in 1998 but are yet to be used in clinical trials.

PMID- 16969446
TI  - The skin and the mind.
AB  - BACKGROUND: The intimate relationship of the skin and the mind illustrates the
      importance of a holistic approach in caring for patients with skin problems.
      Habits related to psychological problems may lead to skin problems such as lichen
      simplex chronicus and acne excoriee. Emotional stress may affect skin diseases
      such as atopic dermatitis, perioral dermatitis, pompholyx, and plaque psoriasis.
      OBJECTIVE: This article describes the relationship between the mind and skin
      disease. DISCUSSION: Skin disease can exert a profound effect on the psychosocial
      dimension of a patient's life. Its effect on quality of life can be objectively
      assessed and documented by validated tools specific for the skin. Patient rated
      measures should be taken into account when evaluating the efficacy and adverse
      effects of treatments for skin disease.

PMID- 16969448
TI  - Medication errors: immunisation.
AB  - Case histories are based on actual medical negligence claims or medicolegal
      referrals, however certain facts have been omitted or changed by the author to
      ensure the anonymity of the parties involved. This article outlines a medication
      error involving childhood immunisation and examines the underlying causes of the
      incident. Advice about how to deal with a patient and their family when things go
      wrong is provided.

PMID- 16969449
TI  - Screening for chlamydia with the Pap test.
AB  - The implementation of the recent National Health and Medical Research Council
      Guidelines for the management of asymptomatic women with screen detected
      abnormalities is welcome and should address the current practice of unnecessary
      repeated investigation of young women infected with human papilloma virus (HPV).
      It is timely to consider the overall benefit of the Pap test in this group for
      whom rates of cervical cancer are extremely low.

PMID- 16969450
TI  - Women's experience of lactational mastitis--I have never felt worse.
AB  - BACKGROUND: Mastitis is a common problem for breastfeeding women in the
      postpartum period. METHODS: Ninety-four breastfeeding women participating in a
      case control study of mastitis provided a free text comment about their
      experience of mastitis. Women were recruited from the emergency department, wards
      or breastfeeding clinics of the Mercy Hospital for Women and the Royal Women's
      Hospital, Melbourne, in 2002-2004. RESULTS: The main themes which emerged from
      the free text comments were: acute physical illness; negative emotions; life
      disrupted; to continue breastfeeding or not? A minor theme was 'support for
      mastitis research'. DISCUSSION: Women with mastitis often experience a rapid
      onset physical illness accompanied by strong negative feelings, which leads some
      women to consider stopping breastfeeding while others are determined to
      persevere. General practitioners need to provide emotional support for women with
      mastitis and acknowledge that breastfeeding may be difficult for new mothers.

PMID- 16969451
TI  - GP wellbeing and general practice issues.
AB  - INTRODUCTION: Studies of general practitioner wellbeing have demonstrated
      remarkably consistent findings. However, the implications for day-to-day general
      practice have been unclear. This study was based on a survey comprising items
      extracted from transcripts of interviews with GPs and designed to link general
      practice issues with self reported wellbeing. METHODS:  PARTICIPANTS: 480 GP
      Australian Family Physician (AFP) subscribers (2.18% response rate); aged 26-81
      years (mean 45.5 years); 273 (56.9%) men and 199 (43.1%) women. MEASURE: A survey
      insert in AFP September 2003 with questions about wellbeing, demographic details
      and 27 items about general practice issues. RESULTS: Almost 15% reported
      poor/very poor wellbeing, 47% reported good wellbeing and 38% reported very
      good/excellent wellbeing. Poor wellbeing was associated with being single,
      divorced or widowed, and reports of being alone in an adversarial context and
      more negative reactions to patients. Excellent or very good wellbeing was
      associated with being coupled and reports of general practice as a vocation.
      DISCUSSION: Targeted wellbeing strategies advocating social support may
      ameliorate the stress of general practice, especially for those GPs who are
      single.

PMID- 16969452
TI  - Managing shoulder pain in general practice--the value of academic detailing.
AB  - After low back pain and neck pain, shoulder pain is the third musculoskeletal
      reason for presentation to general practice, with a self reported prevalence of
      16-26%. Approximately 1% of the adult population is expected to visit a general
      practitioner annually for shoulder pain. Shoulder complaints are more common in
      women and despite the fact that 50% of acute shoulder pain resolves in 8-10
      weeks, many patients present with the anticipation of being referred for imaging.

PMID- 16969453
TI  - Thermotropic lanthanidomesogens.
AB  - Due to their high and variable coordination numbers leading to poorly predictable
      three-dimensional coordination spheres, the trivalent lanthanide metal ions are
      challenging molecular objects for introduction into thermotropic liquid crystals.
      Conversely, their predictive electronic, optical and magnetic metal-centred
      properties make them particularly attractive for being incorporated into
      switchable macroscopic materials responding to external electric and magnetic
      stimuli. We briefly describe here some of the important concepts and strategies
      leading to the recent successful preparation of luminescent thermotropic
      lanthanide-containing mesophases, for which the generic term lanthanidomesogens
      is proposed.

PMID- 16969454
TI  - A unified synthetic approach to the pyrazinone dragmacidins.
AB  - This review describes recent developments from our laboratory involving the
      synthesis of the structurally complex, pyrazinone-containing dragmacidin
      alkaloids.

PMID- 16969455
TI  - Unmodified gold nanoparticles as a colorimetric probe for potassium DNA aptamers.
AB  - Unmodified gold nanoparticles effectively differentiate unfolded and folded DNA,
      thus providing a novel approach to colorimetrically probe aptamer-based
      recognition processes.

PMID- 16969456
TI  - "Click" synthesis of small molecule probes for activity-based fingerprinting of
      matrix metalloproteases.
AB  - By using "Click Chemistry", we achieved the facile synthesis of various affinity
      based hydroxamate probes that enable generation of activity-based fingerprints of
      a variety of metalloproteases, including matrix metalloproteases (MMPs), in
      proteomics experiments.

PMID- 16969457
TI  - A single-bonded cationic terminal borylene complex.
AB  - The cationic terminal borylene complex [(eta5-C5H5)(CO)2FeB(eta5-C5Me5)][AlCl4]
      has been isolated from the reaction of [(eta5-C5H5)(CO)2FeB(Cl)(eta1-C5Me5)] with
      AlCl3 and on the basis of X-ray crystallographic data, spectroscopic data and a
      DFT calculation it is concluded that the B-->Fe bond order is one.

PMID- 16969458
TI  - Oxoneptunium(v) as part of the framework of a polyoxometalate.
AB  - (NH4)14Na4[(Np3W4O15)(H2O)3(BiW9O33)3].62H2O (1) and
      (NH4)14.5Na3.5[(Np3W4O15)(H2O)3(SbW9O33)3].40.5H2O (2) each contain three
      neptunyl(v) moieties encapsulated within heteropolyoxotungstate frameworks in
      which axial {NpO2}+ oxygens form one face of a WO6 octahedron.

PMID- 16969459
TI  - Tuning the properties of cyclen based lanthanide complexes for phosphodiester
      hydrolysis; the role of basic cofactors.
AB  - The synthesis of several cyclen based lanthanide [Eu(III) and La(III)] complexes
      is described; these metallo ribonuclease mimics are based on the use of alkyl
      amines as pendent arms, which give rise to fast hydrolysis within the
      physiological pH range of HPNP (an RNA model compound) that is highly dependent
      on the length of the alkyl spacer.

PMID- 16969460
TI  - Selective monoiodination of aromatic compounds with electrochemically generated
      I+ using micromixing.
AB  - Selective monoiodination of aromatic compounds such as dimethoxybenzene has been
      successfully achieved with I+, which is generated by anodic oxidation of I2 in
      acetonitrile, using micromixing.

PMID- 16969461
TI  - Fast and "green" living cationic ring opening polymerization of 2-ethyl-2
      oxazoline in ionic liquids under microwave irradiation.
AB  - The living cationic ring opening polymerization of 2-ethyl-2-oxazoline performed
      in an ionic liquid under microwave irradiation showed an enhanced polymerization
      rate in comparison to the reaction in common organic solvents; the ionic liquid
      was efficiently recovered and reused in new reaction cycles, completely avoiding
      the use of organic volatile compounds.

PMID- 16969462
TI  - A donor-stabilization strategy for the preparation of compounds featuring P=B and
      As=B double bonds.
AB  - A new class of heavier group 15 compounds demonstrating multiple bonding with
      boron has been synthesized using a simple donor-stabilization protocol.

PMID- 16969463
TI  - Synthesis and structural characterisation of lower rim halogenated
      pyrogallol[4]arenes: bi-layers and hexameric nano-capsules.
AB  - Two lower rim halogenated pyrogallol[4]arenes have been synthesised and
      structurally characterised as either bi-layer or hexameric nano-capsule motifs
      depending upon chain length and functionalisation.

PMID- 16969464
TI  - Desolvation tips the balance: solvent effects on aromatic interactions.
AB  - The folding behaviour of the molecular torsion balance framework is rationalised
      by considering the effects of solvation using the alpha/beta H-bond parameter
      scheme for estimating the free energies of pairwise functional group interactions
      in solution.

PMID- 16969465
TI  - A simple and robust reversible redox-fluorescence molecular switch based on a 1,4
      disubstituted azine with ferrocene and pyrene units.
AB  - Taking advantage of the properties of the ferrocene as a redox and electron donor
      active unit and the pyrene as a fluorescent unit, dyad 2 shows a fast and
      reversible redox-switchable fluorescence emission.

PMID- 16969466
TI  - Alkali-metal-catalyzed addition of primary and secondary phosphines to
      carbodiimides. A general and efficient route to substituted phosphaguanidines.
AB  - Organo alkali metal compounds such as (n)BuLi and (Me3Si)2NK act as excellent
      catalyst precursors for the addition of phosphine P-H bonds to carbodiimides,
      offering a general and atom-economical route to substituted phosphaguanidines,
      with excellent tolerability to aromatic C-Br and C-Cl bonds.

PMID- 16969467
TI  - Early-late heterobimetallic complexes as initiator for ethylene polymerization.
      Cooperative effect of two metal centers to afford highly branched polyethylene.
AB  - Ethylene polymerization initiated by early-late transition-metal complexes
      afforded a polymer with different branched structures and properties depending on
      the type of late transition-metal.

PMID- 16969468
TI  - Photoisomerization as a modulator of the DNA-cleaving efficiency of novel azo
      bispropargyl sulfones.
AB  - Novel azobenzene based bispropargyl sulfones have been prepared in the thermally
      stable E-form: irradiation with a high-pressure Hg lamp converted them to the Z
      isomer which showed higher DNA-cleaving efficiency.

PMID- 16969469
TI  - The promoting effect of energetic activation of a methane molecular-beam in the
      direct catalytic partial oxidation of methane.
AB  - Energetic activation of a methane molecular-beam promoted remarkably the direct
      catalytic partial oxidation on Pt and Rh foils, in particular, hydrogen formation
      was dramatically enhanced.

PMID- 16969470
TI  - Specific interaction of citrate with bis(fluorophoric) bibrachial lariat aza
      crown in comparison with the other components of the Krebs cycle.
AB  - Among the Krebs cycle components, just citrate enhances the fluorescence of a new
      bi(brachial) lariat aza-crown containing appended naphthalene fluorophores.

PMID- 16969471
TI  - Reversible guest molecule encapsulation in the 3-D framework of a
      heteropolynuclear luminescent Zn4Eu2 cage complex.
AB  - Guest molecules of diethyl ether or methanol are reversibly encapsulated in
      cavities formed by the 3-dimensional supramolecular framework of
      heteropolynuclear, luminescent [Eu2Zn4L4(OAc)6(NO3)2(OH)2].2Et2O.

PMID- 16969472
TI  - A cooperative beads-on-a-string approach to exceptionally stable DNA triplexes.
AB  - A poly(dT) oligomer can serve as the string on which synthetic hairpins
      possessing poly(dA) and poly(dT) arms connected by a hydrophobic perylene diimide
      linker are assembled like beads on a string. The synthetic hairpins form head-to
      head dimers and trimers, respectively, in the absence of the poly(dT) string and
      in the presence of a string with inverted polarity at mid-strand. However, they
      assemble in cooperative head-to-tail fashion on normal poly(dT) oligomers.

PMID- 16969473
TI  - Hemilabile behavior of a thioether-functionalized N-heterocyclic carbene ligand.
AB  - The truly hemilabile nature of a novel thioether-functionalized N-heterocyclic
      carbene ligand is demonstrated in a range of Pd(II) complexes.

PMID- 16969474
TI  - Room temperature synthesis of coinage metal (Ag, Cu) chalcogenides.
AB  - Coinage metal chalcogenides in their nanoregime have been synthesized in aqueous
      medium at room temperature by mixing the nanoparticles of silver or copper with
      selenium nanoparticles which are authenticated by UV-vis, XRD and TEM analyses.

PMID- 16969475
TI  - Cystatins in non-small cell lung cancer: tissue levels, localization and relation
      to prognosis.
AB  - Cystatins regulate tumour-associated cysteine proteases, however, their role in
      tumour progression is not clear yet. To assess their relevance in the progression
      of non-small cell lung cancer (NSCLC) the protein level, cysteine protease
      activity (CPI) and localization of type I (stefins A and B) and type II (C, E/M
      and F) cystatins were defined in tumours and control lung counterparts from 165
      patients. The medians of CPI activity, stefins A and B were significantly greater
      in tumour than in lung tissue (2.1-fold, 1.7-fold, 1.2-fold, respectively, all
      p<0.001). The median levels of cystatin C and cystatin E/M were lower in tumour
      tissue (0.9-fold, p=0.06; 0.6-fold, p<0.01). In all the samples the levels of
      cystatin F were below the detection limit. Immunohistochemical analysis revealed
      the presence of all cystatins in tumour cells and infiltrated inflammatory cells
      such as macrophages and neutrophils. In univariate survival analysis patients
      with high levels of stefin A, stefin B and CPI activity exhibited a better
      survival probability (p=0.05, p=0.05, p<0.01, respectively). In contrast,
      cystatins C and E/M provided no prognostic information. In multivariate analysis
      the most powerful predictor of survival was the pTNM stage (p<0.0001; RR 3.5),
      followed by stefin A, stefin B and CPI activity (all p=0.03; RR 1.5). Our results
      suggest that only stefins A and B, i.e. type I cystatins, are up-regulated in
      lung tumours and thus able to counteract harmful tumour-associated proteolytic
      activity. As biological markers they may add independent prognostic information
      for better assessment of low- and high-risk patients with NSCLC.

PMID- 16969476
TI  - Expression of the mutated transketolase TKTL1, a molecular marker in gastric
      cancer.
AB  - The nonoxidative pentose phosphate pathway allows glucose conversion to ribose
      for DNA or RNA synthesis and glucose degradation to lactate controlled by
      transketolase enzyme reactions. It has been postulated, that this pathway is of
      the utmost importance in tumors for the proliferation process. We detected a
      strong upregulation of the mutated transketolase transcript (TKTL1) in a
      considerable number of patients with gastric cancer (GC) or cancer of the
      gastroesophageal junction (GEJ). While only 10.8% of the cancer tissues revealed
      a significant mRNA upregulation, 36.9% of the cancer tissues demonstrated a
      protein overexpression. We propose that TKTL1 upregulation is a common phenomenon
      in GC and cancer of the GEJ leading to an enhanced, oxygen-independent glucose
      usage which might contribute to a more aggressive tumor growth. Since molecular
      targeted inhibition of transketolase enzyme reactions suppresses tumor growth and
      metastasis, TKTL1 could be a relevant target for anti-transketolase therapies in
      gastric cancer.

PMID- 16969477
TI  - Differential expression in histologically normal crypts of ulcerative colitis
      suggests primary crypt disorder.
AB  - Ulcerative colitis is characterized by crypt infiltration particularly of
      neutrophils. However, it is not known whether it reflects a primary crypt
      disorder or a secondary inflammatory response. In this study, we analyzed the
      expression profiles of histologically normal crypts microdissected from formalin
      fixed biopsies of early stage ulcerative colitis. Total RNAs were extracted,
      amplified, and applied to Affymetrix GeneChip(R) X3P Array. For the control,
      similar crypts from nonspecific colitis biopsies were applied. A total of 353
      (4.3%) and 111 (1.4%) genes were >3 times up-, and down-regulated in ulcerative
      colitis. Up-regulated genes included FCGBP (Fc fragment of IgG binding protein),
      cyclophilin A, chemokine (C-X-C motif) ligand 3, and genes associated with lipid
      metabolism. Down-regulated genes included APOA4 (apolipoprotein A-IV),
      cylindromatosis, BCL2-like 10, claudin 8, and numerous transcriptional
      regulators. FCGBP and APOA4 have been implicated in ulcerative colitis
      previously. Our data show differential expression in the crypt epithelia of
      ulcerative colitis before active inflammation is initiated, suggesting primary
      crypt abnormalities that might be implicated in the pathogenesis of ulcerative
      colitis.

PMID- 16969478
TI  - The role of S100A1 in external auditory canal cholesteatoma.
AB  - S100 proteins were reported to be involved in different biological activities
      such as transduction of intracellular calcium signalling. It has been reported
      that each member of the S100 protein family exhibits a distinct tissue-specific
      pattern of expression. Furthermore, altered S100 protein expression and function
      correlate with many diseases. The expression of S100A1 was reported to be
      increased in different tissue with hyperplasia. The external auditory canal
      cholesteatoma (EACC) is a benign hyperplasia of the auditory meatal skin.
      However, without treatment, EACC destroys adjacent tissue. Seventeen EACC
      specimens were collected and investigated immunohistochemically against S100A1.
      Normal auditory meatal skin served as control. In the EACC, S100A1 showed a more
      homogeneous staining pattern, positively expressed throughout the epithelial
      layers. The keratin debris showed no detectable expression of S100A1. In the
      auditory meatal skin (control), S100A1 was only expressed in the basal layer of
      the epithelium. We showed that there are different staining patterns in normal
      auditory meatal skin, middle ear cholesteatoma and external auditory canal
      cholesteatomas. The immunoreactivity increased with the stage of the disease.
      Contrary to that reported previously in the middle ear cholesteatomas, the
      reactivity was strongest in the upper epithelial layers. In our collective, the
      epithelial matrix of the EACC showed strong reactivity throughout all the layers.
      Surprisingly, there is no study regarding the connection between growth factors
      and S100A1. In previous experiments we showed significant increase of growth
      factors in EACC. This correlates with our new data concerning S100A1. This is the
      first study to show the different reactivity pattern of S100A1 in the external
      auditory canal cholesteatoma.

PMID- 16969479
TI  - Assessment of the severity of liver disease and fibrotic change: the usefulness
      of hepatic CT perfusion imaging.
AB  - This study assessed the utility of CT perfusion for quantitative assessment of
      liver function and fibrosis. Tissue blood flow (TBF), tissue blood volume (TBV),
      mean transit time (MTT) and hepatic arterial fraction (HAF) were measured with CT
      perfusion using the deconvolution algorithm in 38 patients with chronic liver
      diseases and 10 patients without liver disease. Using Child-Pugh classification,
      21 patients were classified as Child A, 10 as Child B, and 7 as Child C. In 20
      patients, the degree of fibrosis was quantitated in surgically-resected specimens
      and compared with the perfusion parameters. The mean TBF, TBV, MTT and HAF of
      patients with-out liver disease were 103.9+/-18 ml/min/100 g, 12.5+/-2.0 ml/100
      g, 11.1+/-1.6 sec and 18.4+/-5.6%, respectively (+/-SD). The mean TBF of patients
      with Child A, B and C were 95.1+/-24, 86.7+/-29 and 75.5+/-6.5 ml/min/100 g,
      respectively. TBF tended to decrease with the severity of chronic liver disease.
      The mean HAF of patients with Child A, B and C were 18.6+/-8.3, 29.8+/-11.2 and
      40.2+/-11.1%, respectively. HAF of patients without liver disease was
      significantly different from those of Child B and C (p<0.05, each). However,
      there were no significant differences in TBV and MTT between each groups. HAF
      correlated significantly with the degree of fibrosis (R2=0.588, p<0.05). Our
      results showed that parameters of CT perfusion correlated significantly with the
      severity of liver fibrosis and cirrhosis. Quantitative measurement of hepatic
      tissue blood flow by CT perfusion is useful for evaluation of the severity of
      disease and fibrotic change.

PMID- 16969480
TI  - Genetic progression and divergence in superficial esophageal squamous cell
      carcinoma by loss of heterozygosity analysis.
AB  - Esophageal squamous cell carcinoma (SCC) is one of the most common fatal
      carcinomas worldwide and has some of the most malignant characteristics among
      gastrointestinal tumors. Although a high frequency of loss of heterozygosity
      (LOH) for various genes has been observed in esophageal SCCs, these findings do
      not provide any information regarding the genetic pathways that may underlie the
      development and progression of this type of tumor. To clarify the temporal and
      topographic pathways in the genetic evolution of esophageal SCC, we
      microdissected multiple foci from superficial mucosal invasive foci of tumors. We
      then carried out LOH analyses of the microdissected neoplastic foci. Sixteen
      superficial esophageal SCCs were examined. Three to six carcinoma foci from each
      superficial esophageal SCC were individually microdissected. We used 12
      oligonucleotide primer pairs specific for the microsatellite markers for which
      frequent LOH in esophageal SCC has been reported. All tumors exhibited LOH of at
      least three microsatellite loci. A frequent homogeneous LOH pattern was detected
      for TP53 (60%), D16S518 (43%) and D3S1234 (29%), suggesting that the loss of
      these alleles is an early event in the development of esophageal SCC. A
      heterogeneous LOH pattern was detected for D13S325 (87%), D10S559 (73%), D3S1568
      (58%), D3S1234 (57%) and D3S1621 (56%), suggesting that the loss of these alleles
      is a late event in the development of esophageal SCC. All tumors showed the LOH
      pattern of single clonal neoplasms with genetic progression and divergence. In
      conclusion, by extensive sampling of SCC lesions with microdissection and LOH
      analysis of multiple chromosomal loci, we successfully demonstrated dynamic and
      successive accumulation of genetic alterations in early SCC.

PMID- 16969481
TI  - Vasculogenic mimicry is associated with high tumor grade, invasion and
      metastasis, and short survival in patients with hepatocellular carcinoma.
AB  - Vasculogenic mimicry (VM) has increasingly been recognized as a form of
      angiogenesis. In VM, epithelial cells are integrated into the malignant tumor
      vasculature. An association has been observed between VM and poor clinical
      prognosis in some malignant tumors. However, whether VM is present and clinically
      significant in hepatocellular carcinoma (HCC) is unknown. In this study, we
      determined whether VM was present in HCC and whether it was associated with tumor
      grade, invasion and metastasis, and survival duration. We collected paraffin
      embedded HCC tumor samples, along with complete clinical and pathologic data for
      all the cases, and performed immunohistochemical staining for CD31, CD105
      (endoglin), hepatocyte, vascular endothelial growth factor, matrix
      metalloproteinase (MMP)-2, and MMP-9. The VM status was compared with the
      clinical and pathological data using statistical tests. Kaplan-Meier survival
      analysis and log-rank test were used to compare survival durations between
      patients with and without VM. The VM vessel cells were CD31 and CD105-negative
      and hepatocyte and vascular endothelial growth factor-positive, showing that they
      were not derived from endothelial cells but were HCC tumor cells. Patients with
      VM had a higher metastasis rate than did those without VM (P=0.003). Consistent
      with this finding, MMP-2 and MMP-9 were present in all the VM cases but were
      found less frequently in non-VM cases (P<0.05). The Kaplan-Meier survival
      analysis showed that patients in the VM group had a significantly shorter
      survival duration than did those in the non-VM group. In conclusion, VM is a
      marker of poor clinical prognosis in HCC: Its presence may be associated with a
      high tumor grade, invasion and metastasis, and short survival.

PMID- 16969482
TI  - The S1P receptor modulator FTY720 prevents the development of experimental
      colitis in mice.
AB  - To evaluate the therapeutic effects of the new synthetic sphingosine-1-phosphate
      (S1P) receptor modulator, FTY720, we investigated how FTY720 affects the
      development of dextran sulfate sodium (DSS)-induced colitis and CD4+CD62L+ T cell
      transfer colitis. BALB/c mice were fed a chow containing 3.5% (wt/wt) DSS to
      induce colitis. The CD4+CD62L+ T cell transfer colitis was induced by an
      intraperitoneal injection of CD4+CD62L+ spleen T cells into recipient CB17 SCID
      mice. The FTY720 was administered by lavage at a dose of 0.3 mg/kg/day. FTY720
      was effective in preventing the body weight loss in the DSS-colitis model and the
      CD4+CD62L+ T cell transfer model. The disease activity index, histological
      colitis score, and MPO activity were all significantly lower in FTY720-treated
      mice than in the non-treated mice. Microscopically, mucosal edema, cellular
      infiltration and epithelial disruption were much more moderate in the FTY720
      treated mice than in the non-treated mice. In both colitis models, FTY720
      prevented the infiltration of CD4+ T cells into the inflamed colonic lamina
      propria. In conclusion, the development of DSS-colitis and CD4+CD62L+ T cell
      transfer colitis were significantly attenuated by FTY720. Since FTY720 is an
      immunosuppressive product that does not modulate T cell functions, it could be
      useful in the treatment of IBD patients.

PMID- 16969483
TI  - Proteomic analysis of a highly metastatic gastric cancer cell line using two
      dimensional differential gel electrophoresis.
AB  - Stomach cancer is still a major cause of death in Asian people despite a complete
      cure after the resection of early cancers, mainly because peritoneal
      dissemination is difficult to treat. In the present study, we used two
      dimensional differential gel electrophoresis (2-D DIGE) to identify specific
      proteins differentially expressed between a highly metastatic stomach cancer cell
      line MKN-45-P and its parental cell line MKN-45. We detected 27 protein spots in
      at least 2 of 3 experiments which showed statistically significant differences in
      abundance. All 27 protein spots were identified using matrix-assisted laser
      desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MS) and
      database-searching software. A proteomic analysis revealed 13 different proteins
      with some isoforms sharing different biochemical characteristics, and that 8
      proteins were up-regulated, and 5 were down-regulated. The 13 proteins were
      mainly involved in protein synthesis (transfer RNA synthetase), metabolism
      (flavoprotein subunit, pyruvate kinase, adenylate kinase), receptor and signal
      transduction (annexins I and A2), the cytoskeleton (keratin 5, cytokeratin 8) and
      cell cycling (ts11). These results suggested that a proteomic approach including
      2-D DIGE would be an efficient way to identify the proteins responsible for
      specific biological functions. Moreover, these observations might be novel
      findings leading to the prediction of postoperative peritoneal recurrence.

PMID- 16969484
TI  - Inhibition of murine K-BALB and CT26 tumour growth using a Semliki Forest virus
      vector with enhanced expression of IL-18.
AB  - The enhanced Semliki Forest virus vector (SFV10-E), an RNA-based suicide
      expression vector system, expresses foreign genes at levels up to 10x higher than
      the original SFV10 vector. This vector has been used previously to express
      interleukin-12 for a tumour treatment study in a BALB/c murine model. Interleukin
      18, an IFN-gamma-inducing cytokine, plays a key role in the early induction of T
      helper1 (Th1) cell-mediated immune responses in addition to anti-angiogenic
      activity. In this study, the murine IL-18 gene along with an Ig-kappa leader
      sequence was cloned into the SFV10-E vector. The pSFV10-E-IL-18 construct was
      characterised in vitro for levels of expression and secretion, and the production
      of biologically active IL-18 was confirmed. An in vivo tumour treatment study
      using high titre rSFV10-E-IL-18 virus-like particles to treat subcutaneous K-BALB
      and CT26 tumours in BALB/c mice demonstrated therapeutic efficacy including the
      disappearance of tumour cells in a minority of treated animals. Tumour regression
      was associated with induction of avascular and suppurative necrosis.

PMID- 16969485
TI  - Expression of chemoresistance-related proteins in alpha-fetoprotein-producing
      adenocarcinoma of the digestive organs.
AB  - alpha-fetoprotein-producing adenocarcinoma of the digestive organs (APAD) is
      known to show a poor prognosis. To clarify the characteristics of chemoresistance
      in APAD, three proteins of fluoropyrimidine chemotherapy association
      [dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and
      thymidylate synthase (TS)] and one protein of cisplatin association
      [metallothionein (MT)] were immunohistochemically evaluated. Tissue samples were
      taken from 12 AFP-positive gastric cancers and 94 AFP-negative gastric cancers.
      Four AFP-positive cancer xenografts (one colonic, two pancreatic, and one biliary
      tract) and 17 AFP-negative cancer xenografts were also examined. In gastric
      cancers, high expression of TP was observed in 30% of AFP-negative tumors but in
      none of AFP-positive tumors (p=0.03). High expression of MT was found in 30% of
      AFP-negative tumors but in only one of the AFP-positive tumors. The TP-low and MT
      low phenotype was noted in 92% of AFP-positive tumors and in 46% of AFP-negative
      tumors (p=0.004). None of the AFP-positive cancer xenografts revealed high TP
      expression and only one showed high MT expression. In the cellular level, TP and
      MT were scarcely co-expressed with AFP in either gastric cancer or xenograft
      series, using double immunostaining and serial sectioning techniques. There were
      no significant differences in the expression of DPD and TS between AFP-positive
      group and -negative group. However, DPD was frequently co-expressed with AFP in
      poorly differentiated medullary areas of the AFP-positive gastric cancers. The
      data presented herein suggest that APAD should be sensitive to cisplatin, but
      resistant to capecitabine and 5'-deoxyfluorouridine, fluoropyrimidines which are
      converted to 5-fluorouracil by TP. S-1, a fluoropyrimidine containing a strong
      DPD inhibitor, may be effective for AFP-positive gastric cancers with poorly
      differentiated medullary growth pattern.

PMID- 16969486
TI  - Differential expression of claudin-4 between intestinal and diffuse-type gastric
      cancer.
AB  - Our previous microarray analysis of gastric cancer found that claudin-4 was
      differentially expressed between intestinal-type gastric cancer (IGC) and diffuse
      type gastric cancer (DGC). Claudin-4 is a member of a large family of
      transmembrane proteins, claudins, essential in the formation and maintenance of
      tight junctions. To explore the roles of claudin-4 in the two histologically
      distinct types of gastric cancer, we selected 45 IGC and 48 DGC cases and then
      analyzed the expression of the protein using immunohistochemistry. We found that
      the overexpression of claudin-4 was greater in IGC than in DGC. A trend was
      observed between the overexpression of claudin-4 and lymph node metastasis,
      however, this association was not statistically significant. The results showed
      that the expression of claudin-4 was lower in DGC. Possibly it played a role in
      determining the diffuse phenotype and loose cohesion of cells in DGC in a similar
      manner as E-cadherin.

PMID- 16969487
TI  - Characteristic features of disseminated carcinomatosis of the bone marrow due to
      gastric cancer: the pathogenesis of bone destruction.
AB  - Disseminated carcinimatosis of the bone marrow is accompanied by solid tumors,
      and gastric cancer accounts for the majority. The prognosis of this condition is
      poor, however, the pathogenesis for wide-spread bone lesions has yet to be
      elucidated. In 9 patients with gastric cancer demonstrating disseminated
      carcinomatosis of the bone marrow, the characteristic clinicopathological
      features were examined. Immunohistochemistry for receptor activator of NF-kappaB
      ligand (RANKL) and parathyroid hormone-related protein was also performed on
      gastric cancer tissue and bone marrow specimens to identify the factors
      responsible for the occurrence of bone lesions in patients presenting with this
      condition. The characteristic features of disseminated carcinomatosis of the bone
      marrow due to gastric cancer include a yonger patient age, an elevation of serum
      alkaline phosphatase and/or lactate dehydrogenase levels, wide-spread bone
      metastases with osteolytic bone destruction, a low incidence of hypercalcemia and
      a histological gastric cancer type of either signet ring cell carcinoma or poorly
      diffentiated adenocarcinoma. The expression of RANKL, which is one of the master
      regulators of osteoclastic bone resorption in bone metastasis, was also found in
      gastric cancer cells obtained from such patients. The RANKL expressed in gastric
      cancer may therefore play a critical role in the promotion of osteoclast
      formation, which has been suggested to be involved in the pathogenesis of bone
      lesions.

PMID- 16969488
TI  - Comparison of CD44 expression in primary tumours and metastases of colorectal
      cancer.
AB  - A better understanding on the development of a metastatic phenotype in colorectal
      cancer (CRC) is essential to help identify patients at high risk for metastasis.
      Therefore, we have studied the role of the CD44 family of trans-membrane
      glycoprotein in the process of CRC metastasis, by examining the expression of
      CD44s and CD44v6 in primary tumours and their metastatic lesions in 46 patients
      using immunohistochemistry. The expression of both CD44s and CD44v6 was
      significantly higher (moderate/strong) in primary tumours as compared to their
      metastases (p=0.008, p=0.0001, respectively). CD44s expression in metastases
      increased with the degree of the histological grade (p=0.009) and invasiveness of
      the primary tumour (p=0.002). Disease-free survival (DFS) was shorter in patients
      who had metastases with a strong/moderate expression of CD44s as compared to
      those with negative/weak expression (8.3 months vs 16.9 months p=0.221,
      respectively). Our finding that CD44s expression in metastatic lesions may
      reflect the aggressiveness of the primary tumour from which it has originated
      implicates an important link between the two lesions. CD44 expression may also
      provide valuable biological information as suggested by the observation that up
      regulated CD44s expression in metastases is associated with a shorter DFS.

PMID- 16969489
TI  - Differential expression in normal-adenoma-carcinoma sequence suggests complex
      molecular carcinogenesis in colon.
AB  - The majority of colon cancers develop from pre-existing adenomas. We analyzed the
      expression profiles in the sequence of normal colon crypts, adenomas and early
      stage carcinomas using microdissected cells from tubular adenomas with foci of
      malignant transformation. Differentially expressed genes were detected between
      normal-adenoma and adenoma-carcinoma, and were grouped according to the patterns
      of expression changes in the sequence. Down-regulated genes in the sequence
      included PLA2G2A, TSPAN1, PDCD4, FCGBP, AATK, EPLIN, FABP1, AGR2, MTUS1, TSC1,
      galectin 4 and MT1F. PLA2G2A has been shown to suppress colon tumorigenesis in
      mice, but the pathobiological role in humans has been controversial. Our data
      showed continuous down-regulation of PLA2G2A in the sequence supporting an
      implication in human colon cancer. Tumor suppressor and/ or proapoptotic
      activities have also been reported in other genes. Up-regulated genes included
      ribosomal proteins, IER3 and TPR. TGF-beta2 and matrix metalloproteinase 23B were
      up-regulated in carcinoma but not in adenoma, supporting the pathobiological
      roles in malignant transformation. Differentially expressed genes partly
      coincided with those in the adenoma-carcinoma sequence of the stomach, which was
      published previously, suggesting a partial overlap between the adenoma-carcinoma
      sequences of the colon and stomach.

PMID- 16969490
TI  - AKAPs competing peptide HT31 disrupts the inhibitory effect of PKA on RhoA
      activity.
AB  - A-kinase can inhibit RhoA activation through phosphorylating ser188 of RhoA. AKAP
      is a novel protein that can target PKA to different subcellular compartment.
      Evidence has been presented that PKA anchorage by AKAP is important for the
      kinase to exert its function. This study analyzed the role of PKA anchorage in
      PKA-induced antagonism against RhoA activity and function. The cells transfected
      with pcDNA HT31wt/mut were treated with LPA and/or CPT-cAMP. The amount of GTP
      RhoA and phosphorylation of RhoA was detected by Western blotting with specific
      antibodies. The formation of stress fiber was visualized under fluorescent
      microscope. The gene expression activity was analyzed by luciferase reporter gene
      assay. The motility and the anchorage-independent growth assays were carried out
      with stably transfected cells expressing the AKAP inhibitory peptide HT31. The
      results showed that HT31 not only blocked the PKA-induced phosphorylation of RhoA
      but also prevented the PKA-induced inhibition on RhoA activation. The disruption
      of PKA anchorage abolished its inhibition on the LPA-induced expression of
      reporter gene SRE-luciferase. The ability of PKA to antagonize the LPA-induced
      stress fiber formation was partly impaired upon the disruption of the PKA
      anchorage. The control of PKA on migration and the proliferation excited by LPA
      disappeared in stably transfected cells highly expressing HT31. The results
      revealed that PKA anchorage was necessary for the kinase to exert its inhibitory
      effect on RhoA activation and RhoA-dependent biological activities.

PMID- 16969491
TI  - 99mTc-tetrofosmin SPECT in solitary pulmonary nodule evaluation.
AB  - A correct differential diagnosis between benign and malignant lesions is
      mandatory in patients with solitary pulmonary nodule (SPN). The aim of the
      present study was to investigate whether 99mTc-tetrofosmin SPECT may play a role
      in SPN evaluation. A consecutive series of 111 patients with an uncalcified </=3
      cm (range: 0.8-3 cm) SPN, without definite benign findings and indeterminate at
      CT, were studied. Within 1 week of CT scan, following 740 MBq of 99mTc
      tetrofosmin i.v. injection, all patients underwent chest SPECT using a
      rectangular dual head gamma camera with HR collimators. The images were analysed
      both qualitatively and semiquantitatively by calculating tumor/normal tissue
      ratio (T/N). All nodules were referred to a definitive diagnosis after
      scintigraphy: 84/111 nodules resulted malignant (primary lung carcinomas in 59
      cases and metastases in 25), whereas 27/111 were benign. SPECT was true positive
      in 77/84 malignant nodules (overall sensitivity: 91.7%), detecting 55/59
      carcinomas (93.2%) and 22/25 metastases (88%), whereas it was false negative in 4
      carcinomas (3 adenocarcinomas and 1 squamous cell carcinoma, the latter with
      necrotic areas; range size: 1.5-2.4 cm) and in 3 metastases (range size: 1.0-1.2
      cm). SPECT was true negative in 24/27 benign lesions (specificity: 88.9%) and
      false positive in 2 hamartomas and in 1 aspecific inflammation (range size: 0.8-2
      cm), each with a T/N value </=1.4. Accuracy, positive predictive value and
      negative predictive value were 91, 96.2 and 77.4%, respectively. Mean T/N value
      was significantly higher in malignant than in benign nodules (2.1+/-0.6 vs. 1.3+/
      0.1, P<0.05), whereas no significant differences were observed between primary
      lung carcinomas and metastases (2.1+/-0.6 vs. 1.9+/-0.6) or in the different
      histologic types of carcinomas. 99mTc-tetrofosmin SPECT proved a highly sensitive
      imaging method in both primary and secondary malignant </=3 cm SPNs detection,
      with a high accuracy value in discriminating malignant from benign lesions, also
      by adding semiquantitative analysis. A larger clinical application of this non
      invasive, simple and widely available procedure is thus suggested in SPN
      management, especially when FDG-PET is not available.

PMID- 16969492
TI  - Cyclooxygenase-2 inhibitor, nimesulide, improves radiation treatment against non
      small cell lung cancer both in vitro and in vivo.
AB  - Lung cancer is the leading cause of cancer-related deaths in the United States.
      Despite improvements in radiation, surgery and chemotherapy the 5 year survival
      statistics of non-small cell lung cancer (NSCLC) have improved little over the
      past two decades. It has been proposed that NF-kappaB is a participant in the
      cytoprotection against several redox-mediated therapeutic agents including
      ionizing radiation. Cyclooxygenase-2 (COX-2) inhibition has become an attractive
      target for enhancing the efficacy of radiation and chemotherapy. Numerous
      mechanistic pathways have been proposed as the means through which COX-2
      inhibition enhances the efficacy of radiation. We hypothesize that the COX-2
      inhibitor, nimesulide, will improve the efficacy of radiation therapy (RT), at
      least in part, via the suppression of NF-kappaB mediated cytoprotective pathways.
      In this study we used the COX-2 inhibitor nimesulide to improve the efficacy of
      RT when measured by tumor regrowth assays in vivo and clonegenic survival in
      vitro. For the in vivo assay, A549 tumor cells representing NSCLC were
      subcutaneously injected into the right flanks of female athymic nude mice
      (n=10/group). Mice were given nimesulide via drinking water at a concentration of
      5 microg/g body weight (b.w.) and the water was replenished daily. Tumors were
      treated with 30 Gy fractionated radiation and measured bi-weekly. For our in
      vitro study, clonogenic survival assays were evaluated to determine the effect of
      nimesulide, radiation, and the combination. The NF-kappaB mediated mechanism of
      nimesulide was measured by Western blot analysis of NF-kappaB target genes, MnSOD
      and survivin. In vivo, mice that received combined treatments of 5 microg/g b.w.
      nimesulide and 30 Gy radiation (3 Gy/fraction, 10 daily fractions) had
      significant reduction in tumor size in comparison to the 30 Gy radiation control
      group (p<0.05). In vitro, nimesulide alone produced a significant decrease in
      clonogenic survival at doses from 0-300 microM. Nimesulide demonstrated an
      additive effect in combination with radiation. Nimesulide alone reduced MnSOD and
      survivin protein levels in a dose-dependent manner. 6 Gy radiation caused an
      initial elevation of MnSOD protein levels which was inhibited by prior treatment
      of nimesulide suggesting an inhibition of radiation induced NF-kappaB target
      genes. These results support the hypothesis that COX-2 inhibitors such as
      nimesulide can increase the efficacy of radiation therapy. In vitro, our results
      suggest that the radiosensitization of A549 tumor cells by nimesulide is mediated
      by the suppression of NF-kappaB-mediated, radiation-induced cytoprotective genes.

PMID- 16969493
TI  - Thymidine phosphorylase levels and dihydropyrimidine dehydrogenase levels in non
      small cell lung cancer tissues.
AB  - Thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) are the
      major catabolic enzymes of 5-FU. In this study, we analyzed the concentration of
      TP and DPD in non-small cell lung cancer tissue by enzyme-linked immunosorbent
      assay. We measured the TP and DPD levels in 25 adenocarcinoma tissues and 25
      squamous cell carcinoma tissues. The mean TP concentration in non-small cell lung
      cancer tissue was statistically higher than that of normal lung tissue as was the
      mean DPD concentration. The ratio of the TP level to DPD level in tumor tissue
      was higher in squamous cell carcinoma than in adenocarcinoma. No significant
      difference could be detected between the TP level, DPD level, or TP/DPD level and
      the tumor size or lymph node metastasis. In conclusion, chemotherapy with 5-FU
      may be more effective in squamous cell lung cancer patients than lung
      adenocarcinoma patients from the result of the ratio of TP to DPD.

PMID- 16969494
TI  - Breast cancer risk and polymorphisms in genes involved in metabolism of estrogens
      (CYP17, HSD17beta1, COMT and MnSOD): possible protective role of MnSOD gene
      polymorphism Val/Ala and Ala/Ala in women that never breast fed.
AB  - Polymorphisms in genes encoding enzymes involved in estrogen metabolism are held
      to be candidates for associations with breast disease, since there is evidence
      that circulating estrogens are associated with breast cancer risk. In this study,
      we evaluated the frequency of different polymorphisms related with estrogen
      metabolism [COMT Val158Met, CYP17 (5'UTR, T27C); HSD17beta1 Gly313Ser and MnSOD
      Val16Ala] in a breast cancer resistant population, the Xavante Indians, and the
      frequencies were compared with the ones reported in other populations where
      breast cancer case-control studies dealing with these polymorphisms have been
      carried out. The data obtained showed that, apart from the MnSOD Val16Ala
      polymorphism where the frequency of the variant allele was much higher than that
      reported in other populations, all the others were within the range reported in
      other populations. Considering these data we carried out a case-control study in
      the Portuguese population (241 cases and 457 controls) in order to evaluate the
      potential role of this polymorphism in breast cancer susceptibility. The results
      obtained did not reveal a significant association between individual genotypes
      and breast cancer risk. However, when the population was stratified for breast
      feeding, it was observed that for the patients that never breast fed the presence
      of the variant allele (Ala) was marginally associated with a decreased risk for
      this pathology (adjusted OR: 0.575 (0.327-1.011). These data seem to suggest that
      individuals who never breast fed with MnSOD Val16Ala variant allele are at a
      lower risk for breast cancer, but larger studies are required to confirm these
      results.

PMID- 16969495
TI  - Epidermal growth factor induction of resistance to topoisomerase II toxins in
      human squamous carcinoma A431 cells.
AB  - Alteration of the epidermal growth factor (EGF) signaling pathway occurs
      frequently in human cancer cells and may subsequently affect the cell survival
      towards anti-cancer agents. To elucidate the effect of long-term EGF treatment on
      the chemo-sensitivity of human cancer cells, human squamous carcinoma A431 cells
      (AP) were incubated continuously with 50 ng/ml EGF for 30 weeks and these cells
      were designated as the AC cells. The long-term EGF treatment did not alter the
      EGFR level and the EGF-induced protein tyrosine phosphorylation pattern in the AC
      cells. By MTT assay, the AC cells were shown to be more resistant than the AP
      cells to doxorubicin, etoposide and amsacrine but not to cisplatin. Among the
      drug-resistant proteins, topoisomerase IIalpha (topoII) was downregulated in the
      AC cells while there was no apparent change in the levels of P-glycoprotein, MRP
      1 or glutathione- S-transferase-pi as compared to the AP cells. Furthermore,
      knockdown of topoII by antisense topoII oligonucleotide transfection decreased
      the sensitivity to doxorubicin, etoposide and amsacrine in the A431 cells.
      Results from the present study support an idea that long-term treatment with EGF
      may induce drug resistance in cells through the downregulation of topoII.

PMID- 16969496
TI  - Disruption of protein-protein interaction in the Mgl-1 oncoprotein.
AB  - Mammalian homologues of the Lethal giant larvae (Lgl) tumor suppressor gene have
      been identified and these homologues can complement the yeast double mutant of
      Sop1 and Sop2, the yeast homologue of Lgl, as reported previously. In the absence
      of these genes in yeast, cellular viability is affected at restrictive
      temperature and salt environments. Members of this family contain five or more of
      the WD-40 repeat motifs, which is known to be involved in protein-protein
      interaction. In order to investigate the biochemical roles for conserved amino
      acids within the most conserved WD-40 repeat motif amongst these family members,
      we generated deletion mutants for five conserved amino acids (G450, H451, D453,
      W459 and D460) in mouse Lgl-1 (Mgl-1), located between 450-460 amino acids. We
      found that the deletion mutants of Mgl-1, DeltaG450 and DeltaD453, were not
      capable of complementing yeast mutants of Sop1 and Sop2 at restrictive
      temperature and high salt environments. These results indicate that the WD-40
      repeat motif is important for cellular viability by regulating temperature
      sensitivity and salt tolerance in yeast.

PMID- 16969497
TI  - Linkage disequilibrium of UGT1A1 *6 and UGT1A1 *28 in relation to UGT1A6 and
      UGT1A7 polymorphisms.
AB  - UDP-glucuronosyltransferase (UGT) enzymes are responsible for the glucuronidation
      and detoxification of many endogenous or exogenous xenobiotics. Gilbert's
      syndrome (GS) and Crigler Najjar syndrome type 2 (CNS-II) are characterized by
      unconjugated hyperbilirubinemia due to reduced enzymatic activity of UGT1A1.
      Recent studies have demonstrated the frequent co-existence of UGT1A1 *28 (-53
      [TA]6>7) with other polymorphisms of UGT1A6 and UGT1A7. This finding suggests the
      occurrence of linkage disequilibrium (LD) among UGT1A1, UGT1A6 and UGT1A7
      polymorphisms. UGT1A1 *6 (211G>A, G71R) and UGT1A1 *28 are common in Asian
      populations. In the present study, we investigated the LD of UGT1A1 *6 and UGT1A1
      *28 in relation to UGT1A6 and UGT1A7 polymorphisms. Exon 1 of UGT1A1, UGT1A6 and
      UGT1A7 was sequenced using genomic DNA isolated from peripheral leukocytes of 390
      Japanese subjects. LD and haplotypes were analyzed using SNPAlyze ver. 5.0
      software. UGT1A1 *6 had a strong LD in relation to UGT1A6 variants including
      541A>G and 552A>C (D'=0.846-0.848, r(2)=0.413-0.438) and UGT1A7 variants
      including 387T>G, 391C>A, 392G>A and 622T>C (D'=0.667-0.858, r(2)=0.207-0.413).
      UGT1A1 *28 had a lower degree of LD than UGT1A1 *6 in relation to these variants
      (D'=0.245-0.401, r(2)=0.025-0.063). All the haplotypes with G71R lacked 
      53[TA]6>7. The present study showed for the first time that the LD of UGT1A1 *6
      in relation to UGT1A6 and 1A7 polymorphisms is far stronger than UGT1A1 *28. The
      UGT1A1 *6 allele appears to be independent of the UGT1A1 *28 allele. Although
      patients with GS and CNS-II are believed to have good prognosis, a subgroup of GS
      or CNS-II patients with the UGT1A1 *6 polymorphism might be at risk of abnormal
      drug metabolism and of developing malignant disease.

PMID- 16969498
TI  - Evaluation of Ki67, p53 and angiogenesis in patients enrolled in a randomized
      study of neoadjuvant chemotherapy with or without cystectomy: a Southwest
      Oncology Group Study.
AB  - In this prospective biomarker study, we evaluated the prognostic significance of
      Ki67, p53 and angiogenesis in patients with locally advanced bladder cancer. The
      patients were volunteers from a Southwest Oncology Group trial of locally
      advanced bladder cancer who were randomized to treatment with neoadjuvant
      chemotherapy plus cystectomy or cystectomy alone. Tissue specimens were obtained
      prior to neoadjuvant chemotherapy from 42 patients randomized to receive the
      combination-treatment arm and 52 randomized to cystectomy alone. The statistical
      power of the study was quite limited by the small sample size. The biomarkers
      were assayed by immunohistochemistry. Angiogenesis was determined using anti-CD34
      immunostaining. Patients whose tumors had increased Ki67 expression had better
      progression-free survival that was marginally significant, p=0.063. The median
      survival in those with higher Ki67 expression was 73 months, and in those with
      lower expression was 38 months. However, this did not achieve statistical
      significance, p=0.25. There was a suggestion of worse survival among patients
      whose tumors exhibited altered p53 staining [hazard ratio (HR) = 1.48; p=0.15],
      but there was no difference in progression-free survival (HR=1.02; p=0.93). The
      enumeration of tumor microvessels did not provide prognostic information.

PMID- 16969499
TI  - Missense mutations of BRCA1 gene affect the binding with p53 both in vitro and in
      vivo.
AB  - Women with BRCA1 gene mutations have an increased risk for breast and ovarian
      cancer (BOC). Classification of missense variants as neutral or disease causing
      is still a challenge and has major implications for genetic counseling. BRCA1 is
      organized in an N-terminal ring-finger domain and two BRCT (breast cancer C
      terminus) domains, involved in protein-protein interaction. The integrity of the
      C-terminal, BRCT repeat region is also critical for BRCA1 tumor suppressor
      function. Several molecular partners of BRCA1 have so far been identified; among
      them, the tumor suppressor protein p53 seems to play a major role. This study was
      aimed at evaluating the impact of two missense mutations, namely the W1837R and
      the S1841N, previously identified in BOC patients and located in the BRCT domain
      of the BRCA1 gene, on the binding capacity of this protein to p53. Co
      immunoprecipitation assays of E. coli-expressed wild-type and mutated BRCTs
      challenged with a HeLa cell extract revealed, for the S1841N variant a
      significant reduction in the binding activity to p53, while the W1837R mutant
      showed an inverse effect. Furthermore, a clonogenic soft agar growth assay
      performed on HeLa cells stably transfected with either wild-type or mutant BRCA1
      showed a marked decrease of the growth in wild-type BRCA1-overexpressing cells
      and in BRCA1S1841N-transfected cells, while no significant changes were detected
      in the BRCA1W1837R-transfected cells. These results demonstrate that: i) distinct
      single nucleotide changes in the BRCT domain of BRCA1 affect binding of this
      protein to the tumor suppressor p53, and ii) the two missense mutations here
      described are likely to play a role in breast tumorigenesis. We suggest that in
      vitro/in vivo experiments testing the effects of unclassified BRCA1 gene variants
      should therefore be taken in to consideration and that increased surveillance
      should be adopted in individuals bearing these two BRCA1 missense alterations.

PMID- 16969500
TI  - Genome-wide cDNA microarray screening of genes related to survival in patients
      after curative resection of non-small cell lung cancer.
AB  - We conducted a study to determine whether the expression levels of genes in
      tumors were correlated with the survival of patients after complete resection of
      non-small cell lung cancer (NSCLC). The expression levels of 1176 genes in
      resected tumor specimens from 28 patients were analyzed using the Atlastrade mark
      Human Cancer 1.2 Array. The pathological stages of the resected tumors were I, II
      and III in 14, 5 and 9 patients, respectively. We compared the differences of
      gene expression between patients who survived (n=12) and those who died (n=16).
      The expression levels of cyclin-dependent kinase 8, phosphoinositide-3-kinase,
      interferon regulatory factor 3 and tubulin were significantly higher in the
      tumors of surviving patients with stage I lung cancer (p<0.01). The expression
      levels of 12 genes, including the interferon- stimulated genes, were
      significantly higher in surviving patients with stage II or III lung cancer
      (p<0.01). Stepwise multivariate regression analysis revealed that 4 and 12 genes
      in stage I and stage II/III cancers, respectively, were independent prognostic
      factors (p<0.01). In conclusion, these survival-related genes are considered to
      be possible targets of adjuvant therapy after surgical resection of NSCLC.

PMID- 16969501
TI  - Relationship between E-cadherin, matrix metalloproteinase-7 gene expression and
      clinicopathological features in gastric carcinoma.
AB  - We investigated whether the abnormal expression of E-cadherin (ECD), in
      conjunction with the overexpression of matrix metalloproteinase-7 (MMP-7), is
      correlated with clinicopathological parameters such as metastasis and the
      prognosis for human gastric carcinoma. Using RT-PCR, we examined the expression
      of ECD and MMP-7 mRNA in 42 gastric carcinoma tissues and in the surrounding non
      neoplastic mucosa. The macroscopic and histopathological tumor findings and the
      survival rates were obtained from the patient records. The level of ECD mRNA
      expression was lower in most of the neoplasms as compared to the corresponding
      non-neoplastic tissues (50 vs. 80.9%, respectively). The abnormal expression of
      ECD mRNA was significantly correlated to the microscopic classification and lymph
      node metastases (p<0.05), and its stage (p<0.05). The level of MMP-7 mRNA
      expression was higher in most neoplasms compared to the corresponding non
      neoplastic tissues (66.6 vs. 50%, respectively). The overexpression of MMP-7 mRNA
      was significantly correlated with the microscopic classification, lymph node
      metastases (p<0.05), and its stage (p<0.01). However, a correlation between the
      abnormal expression of ECD and the overexpression of MMP-7 was not obtained. The
      survival rate of the patients with an ECD mRNA expression was longer than that of
      the patients without this expression, but this finding was not statistically
      significant (p=0.2162). The survival rates of patients with MMP-7 mRNA expression
      was significantly shorter than that of the patients without MMP-7 mRNA expression
      (p=0.0025). Overexpression of MMP-7 may be considered as a useful marker for
      determining metastasis and the prognosis of human gastric carcinoma rather than
      the abnormal expression of E-cadherin.

PMID- 16969502
TI  - Androgen receptor negatively influences the expression of chemokine receptors
      (CXCR4, CCR1) and ligand-mediated migration in prostate cancer DU-145.
AB  - We previously reported that androgen receptor (AR) plays a role in the regulation
      of adhesion to the extracellular matrix and invasion of human prostate cancer
      cells by influencing the expression of specific integrin subunits. It is now
      considered that chemokines play a significant role in organ-selective cancer
      metastasis. In this study, we hypothesized that AR may influence the expression
      of these chemokine receptors and cell function. The mRNA expression of chemokine
      receptors in human prostate cancer cell line DU-145 and DU-145 cells expressing
      AR (DU-145/AR) was investigated by RT-PCR. DU-145 cells selectively expressed
      CXCR4 and CCR1 mRNA at high levels compared with DU-145/AR cells. DU-145 showed
      vigorous migratory responses to its ligand CXCL12 (also called stromal-derived
      factor-1alpha, SDF-1alpha) and CCL3 (also called macrophage inflammatory protein
      1, MIP-1alpha). In contrast, neither CXCL12 nor CCL3 affected the migration of DU
      145/AR cells. These results indicate that expression of AR down-regulates the
      migratory responses of human prostate cancer cells via chemokine and its receptor
      systems.

PMID- 16969503
TI  - Aging of patients with hepatitis C virus-associated hepatocellular carcinoma:
      long-term trends in Japan.
AB  - The incidence of hepatocellular carcinoma (HCC) in Japan has been increasing. The
      aim of the present study was to analyze epidemiological changes in Japanese HCC
      patients. A total of 463 patients with HCC diagnosed at our hospital between 1982
      and 2001 were recruited for this study. Cohorts of patients with HCC were
      categorized into intervals of five years. The number of HBV- and HCV-associated
      HCC cases had decreased and increased in 1987-1991, respectively, and thereafter
      reached a plateau. The mean age of patients at diagnosis of HCV-associated HCC
      showed a steady significant increase from 60 to 68 years of age during the
      period, suggesting that these findings were associated with a shift toward an
      older-age group that had the highest rate of HCV infection. The mean age of
      patients with other types of HCC did not significantly change during the period.
      Since it is known that the prevalence of HCV infection in young Japanese persons
      is low and that the incidence of HCV infection is very low at present, our
      findings may indicate that the prevalence of HCC will decline in Japan, an
      advanced country with regard to HCV-associated HCC, in the near future.

PMID- 16969504
TI  - MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers.
AB  - MicroRNAs (miRNAs) are endogenously expressed RNAs 18-24 nucleotides in length
      that regulate gene expression through translational repression by binding to a
      target mRNA. It is thought that the expression level of miRNAs, which act like
      antioncogenes, is frequently reduced in cancers because of chromosome deletion
      and epigenetic changes. Since the processing of miRNAs has been characterized to
      be enzymatic in nature, the expression levels of miRNAs are closely associated
      with the activity and levels of such enzymes. Here, we found that miRNA 143 and
      145 expression levels were extremely reduced in colon cancer cells and commonly
      in the other kinds of cancer cells tested. The transfection of each precursor
      miRNA into the cells demonstrated a significant growth inhibition in human colon
      cancer DLD-1 and SW480 cells, and ERK5 was determined to be the target gene of
      miRNA 143. Since the presence of genomic loci of the miRNAs was confirmed by PCR
      in the cell lines and the precursor miRNAs exhibited a growth inhibitory effect
      in DLD-1 and SW480 cells, the early processes such as transcription and enzymatic
      modification from primary miRNAs to precursor miRNAs seemed to be commonly
      disturbed. These findings indicate that the miRNAs 143 and 145 could become good
      tumor markers and provide an important clue in the study of the mechanism of
      oncogenesis involving miRNAs.

PMID- 16969505
TI  - Regulatory roles of cell surface sialylation in sphingolipid-induced cell death
      in human B cell lymphoma.
AB  - Sphingolipid metabolites are important regulators of cell growth and death. In
      the present study, we examined the function of cell surface sialic acid in
      exogenous sphingosine-1-phosphate (S-1-P) or sphingosine-induced cell death. HBL
      2 human diffuse large B cell lymphoma cells were incubated with or without Vibrio
      Cholerae neuraminidase followed by S-1-P or sphingosine. Flow cytometric analysis
      using Limax flavus agglutinin, a sialic acid-specific lectin, showed that
      sialylated glycoconjugates are present on the surface of HBL-2 cells and that
      they were removed by neuraminidase. In addition, the pretreatment with
      neuraminidase enhanced S-1-P- and sphingosine-induced cell death, an effect that
      was not dependent on caspase activation. Furthermore, the cell death induced by S
      1-P and sphingosine was morphologically distinct from apoptosis. We further
      examined S-1-P-induced cell death in two clones of HBL-8 Burkitt lymphoma cells
      with different amounts of cell surface sialic acid. Clone 3G3, which is
      hypersialylated, was less sensitive to S-1-P than the 3D2 clone, which is
      hyposialylated, suggesting that the extent of surface sialylation influences the
      sensitivity to S-1-P. In conclusion, S-1-P and sphingosine induce cell death, and
      the sensitivity of human B lymphoma cells to these agents appears to depend on
      the amount of sialic acid on their cell surfaces.

PMID- 16969506
TI  - Skewed X chromosome inactivation of blood cells is associated with early
      development of lung cancer in females.
AB  - The skewed X chromosome inactivation (SXCI) was found mainly in adult females. It
      has been linked to development of ovarian and breast cancers. The present study
      aimed to describe the relationship between SXCI and development of lung cancer in
      females. DNA was isolated from blood cells from patients with primary lung cancer
      (n=148) and reference subjects (n=289). The androgen receptor (AR) gene exon 1
      was amplified, with its products from different alleles resolved on denaturing
      polyacrylamide gels and visualized by silver staining. The corrected ratio (CR)
      between products from AR alleles after and before HpaII pretreatment was
      calculated. Occurrence of SXCI was detected in both the patients and reference
      subjects at similar frequency. However, the phenomenon was more frequent in the
      patients below 40 years compared to the corresponding reference group, either
      taking CR >/=3 (25 and 5.8%, respectively; P=0.048) or CR >/=10 as the criterion
      of SXCI (16.7 and 0.8%, respectively; P=0.022). A higher frequency of SXCI was
      also found in the patients below 50 years compared to that for the corresponding
      reference group when CR >/=10 adopted as the criterion (7.9 and 1.2%,
      respectively; P=0.046). The cancer patients with SXCI were more than 10 years
      younger in average age than those without SXCI. SXCI of blood cells is associated
      with early development of lung cancer in females. The X chromosomal inactivation
      assay, therefore, may be used to screen for females predisposed to malignancies
      including lung cancer.

PMID- 16969507
TI  - Alternating hepatic arterial infusion and systemic chemotherapy for stage IV
      colorectal cancer with synchronous liver metastasis.
AB  - Among 41 patients with synchronous liver metastases of colorectal cancer, 15
      patients underwent synchronous resection of their liver metastases and achieved a
      median survival time (MST) of 1,441 days (versus 748 days for the 26 patients
      without resection, p=0.038), a median relapse-free survival time of 652 days (MST
      not reached), and a recurrence rate in the residual liver of 20% (3/15 patients).
      The alternating hepatic arterial infusion and systemic chemotherapy showed
      partial response (PR) in 6 cases, stable disease (SD) in 8 cases, and progressive
      disease (PD) in 1 case (n=15/26). They had an objective response rate of 40%
      (6/15), tumor control rate (>/= SD) of 93.3% (14/15), one-year progression-free
      survival rate of 35.7%, 50% time to progression of 270 days, one-year survival
      rate of 76.2%, and two-year survival rate of 50.8% (MST not reached). Grade 3
      leucopenia was observed in 2/15 patients (13.3%). These results suggest that the
      present alternating therapy may become a standard regimen for patients in whom
      synchronous resection of liver metastases is impossible and patients who have
      stage IV colorectal cancer with a risk of recurrence in the remnant liver and/or
      at extrahepatic sites such as the lungs.

PMID- 16969508
TI  - Analgesic activity of high-dose intravenous calcitonin in cancer patients with
      bone metastases.
AB  - We undertook a prospective, nonrandomized study with the objective to evaluate
      the efficacy of salmon calcitonin (sCT) in controlling pain secondary to bone
      metastases. Our study population consisted of 45 cancer patients with bone
      metastases (26 men) with a mean age of 64 years (range, 48-70) who had completed
      chemotherapy, hormonal therapy and radiation therapy at least 30 days prior to
      enrollment in the study, and had intractable pain despite the use of common
      analgesics (acetaminophen, nonsteroidal anti-inflammatory agents, opioids) and
      bisphosphonates. The study medication was a 300-IU dose of sCT administered
      intravenously daily for 5 consecutive days and repeated every two weeks until no
      response was noticeable. The analgesic efficacy of sCT was evaluated by means of
      Huskisson's visual analogue scale and Keele's pain scale; the daily consumption
      of analgesic drugs and performance status were also monitored. None of the
      patients managed to completely discontinue the use of other analgesics, but 5
      patients (11% of the total number) had an analgesic response that lasted 4 weeks
      and less than 5% of the patients continued to respond for 6 weeks. No significant
      side effects were observed. Our data show that intravenous calcitonin
      administered in a relatively high dose has a very limited therapeutic potential
      as an adjuvant analgesic for a short period of time in selected cancer patients
      with bone metastases.

PMID- 16969509
TI  - A phase II trial with gemcitabine and paclitaxel for the treatment of refractory
      and relapsed multiple myeloma patients.
AB  - Multiple myeloma (MM) is an incurable disease with a 10-year survival of <20%. We
      have previously shown that the combination of gemcitabine and paclitaxel acts
      synergistically to induce apoptosis of myeloma cells in vitro. Based on these
      preclinical studies and phase I-II clinical trials in patients with solid tumors,
      we initiated a phase II clinical trial of paclitaxel 150 mg/m(2) IV over 3 h
      followed by gemcitabine 3000 mg/m(2) IV over 30-60 min in patients with relapsed
      or refractory MM. This regimen was administered every two weeks for a total of
      six cycles. Twelve patients enrolled, 3 discontinued treatment after 1 or 2
      cycles because of severe neutropenia. As a result the protocol was modified to
      reduce the starting dose of gemcitabine to 2,000 mg/m(2). This resulted in
      tolerable hematological and mild non-hematological toxicities in the rest of the
      patients. One patient died before the onset of treatment. Of the 8 remaining
      patients treated with a reduced dose of gemcitabine, 1 achieved a durable CR, 3
      had PR, 1 had minor response (MR), 1 had stable disease and 2 had progressive
      disease. The CR patient had a 98% reduction in the M-protein, beta2-microglobulin
      and plasma cells. His CR continued for more than 6 months. The 3 PR patients had
      a >50% reduction in the M-protein and >40% reduction in beta2-microglobulin. Bone
      marrow plasma cells were reduced by >50% in these patients. Treatment with the
      combination of paclitaxel and gemcitabine is an active and well-tolerated regimen
      in patients with relapsed or refractory multiple myeloma.

PMID- 16969510
TI  - Antitumor and antiangiogenic activity of soy isoflavone genistein in mouse models
      of melanoma and breast cancer.
AB  - Tumor invasion, angiogenesis and metastasis involve secretion of proteolytic
      enzymes and cell migration into blood vessels. Tumor cells are capable of
      degrading the extracellular matrix via a proteolytic cascade that includes
      urokinase-type plasminogen activator (uPA) and matrix metalloproteases (MMPs). We
      have investigated the antitumor and antiangiogenic properties of soy isoflavone
      genistein in B16 melanoma and F3II mammary carcinoma mouse models. At non
      cytotoxic concentrations (0.1-50 microM) genistein induced dose-dependent spindle
      cell morphology and significantly reduced motility in both cell lines. Genistein
      inhibited uPA secreted by F3II cell monolayers, while inducing an increase in the
      proteolytic activity of B16 cells. On the contrary, the compound did not modify
      the MMP-9 and -2 produced by tumor cells. In vivo, i.p. administration of
      genistein at a dose of 10 mg/kg/day reduced tumor-induced angiogenesis in
      syngeneic mice implanted with B16 or F3II cells. Similar antiangiogenic effects
      were obtained with a soybean-based diet. This data suggest that tumor cell
      migration and proteolysis may be associated with the antitumor and antiangiogenic
      activity of soy isoflavone genistein.

PMID- 16969511
TI  - Proliferation studies on chromosome preparations of bone marrow in hematological
      disease.
AB  - The growth rate of neoplastic cells has been the subject of numerous scientific
      and diagnostic approaches. The study presented here analyses the relationship
      between mitotic activity in standardised cytogenetic bone marrow preparations
      from three haematological diseases and diagnostic and clinical parameters, most
      importantly the outcome. The disorders studied were: Acute lymphoblastic leukemia
      (ALL) (N=107), chronic myeloid leukemia (CML) (N=166) and aplastic anemia in
      childhood (AA) (N=39). A strict protocol of quantitative standardisation of
      cytogenetic slides was adhered to ensuring comparability both cross-sectionally
      and longitudinally. The samples were studied after short-term incubation without
      mitogenic in vitro stimuli. The most important findings include: i) ALL:
      Immunological subtypes can be differentiated according to their proliferation
      profile; there is a striking difference between childhood and adult ALL in
      proliferation activity; most importantly initial proliferation is much higher in
      patients who will relapse than in those with stable remission. ii) CML:
      Philadelphia-positive CML shows proliferation activities quite distinct from
      Philadelphia-negative CML; however there is only a small change in the
      proliferative activity from the chronic phase to the accelerated phase or blast
      crisis. iii) AA: Very low proliferation scores rise quickly to near normal levels
      during immunosuppressive therapy in most patients. Higher levels at diagnosis are
      associated with a faster and better response to therapy. In conclusion,
      assessment of the proliferative activity in cytogenetic preparations made from
      bone marrow samples of patients with haematological disease may add valuable
      information as to diagnostic sub-groups and clinical course and may contribute to
      therapeutic decisions.

PMID- 16969512
TI  - Time course of enhanced activity of deoxycytidine kinase and thymidine kinase 1
      and 2 in cultured human squamous lung carcinoma cells, SW-1573, induced by gamma
      irradiation.
AB  - Single high dose rate irradiation of 4 Gy in SW-1573 cells, derived from non
      small cell lung cancer, led to increased activities of deoxycytidine kinase (dCK)
      and thymidine kinase 1 and 2 (TK1 and 2). The activity of dCK increased by
      approximately 30% between 1 and 5 h after irradiation, after which the activity
      returned to the level of control cells by 8 h after irradiation. TK1 activity
      also increased by 30-50% between 1 and 6 h after irradiation. The decline to
      normal levels of dCK concurred with a further increase in the activity of TK1, 8
      h after irradiation. TK2 activity was below control levels during the first 4 h
      after irradiation but rose 3-fold at 8 and 16 h after treatment. The activities
      of TK1 and TK2 had returned to approximate control levels 24 h after irradiation.
      The observation that mitochondrial TK2 activity increased to a very high level
      after irradiation may indicate that the activity of this enzyme is not only
      important for the damage to mitochondrial DNA, the increased activity may also be
      instrumental for repair of damage to nuclear DNA. We presume that the increase in
      activity of TK1 after irradiation is limited to cells in S-phase. Recruitment of
      cells into S-phase, to replace cells killed by irradiation, is probably too slow
      to offer an explanation for the enhanced activity of TK1 8 h after irradiation.
      The increase in activity of both dCK, and TK1 and 2 might be involved in an
      adaptive response of the cells to radiation by facilitation of DNA repair. The
      expression of protein kinase C (PKC) decreased during the first 5 h after
      irradiation. At 5 h after irradiation the level of expression had decreased by
      >50%. The decrease in PKC expression is concurrent with the increase in dCK
      activity. This suggests a role of PKC in the signal transduction from DNA damage
      to the increase in activity of enzymes instrumental in DNA repair.

PMID- 16969513
TI  - Paclitaxel and ceramide synergistically induce cell death with transient
      activation of EGFR and ERK pathway in pancreatic cancer cells.
AB  - The molecular and cellular mechanism of the development of pancreatic cancer is
      under constant and intensive study, and yet the cure is still out of reach. While
      surgical treatment is optional, conventional chemotherapy or chemo-radiotherapy
      remains the best choice. Among others, paclitaxel is proven to be a popular and,
      to a certain extent, effective chemotherapy agent. We proposed that the
      combination of paclitaxel and membrane permeable ceramide would enhance the
      fatality of cancer cells, and reported that the combination increased cell death
      of both head and neck and leukemic cancer cells. In this study, we treated
      pancreatic cancer cells (L3.6 cells) with paclitaxel and ceramide at the
      concentrations of clinical relevance, and treatment was then followed up with an
      investigation of the molecular mechanism of the synergism of paclitaxel and
      ceramide. The results of Western blot analysis indicated that the combo
      synergistically induced ERK and JNK phosphorylation, but not p38 and Akt
      phosphorylation. We also found that the combination (combo) induced EGFR
      phosphorylation in a synergistic manner. Furthermore, we observed that
      paclitaxel, ceramide, or combo-induced EGFR phosphorylation was inhibited by EGFR
      inhibitor, PD153035, while paclitaxel, ceramide, or combo-induced JNK and ERK
      phosphorylation was blocked by EGFR inhibitor, PD153035 and ERK inhibitor, U126.
      Taken together, our results demonstrated that the combination of paclitaxel and
      ceramide synergistically induced pancreatic cancer cell death through
      differential activation of EGFR-mediated MAP kinases. EGFR and ERK inhibitors may
      further enhance the paclitaxel and ceramide effect.

PMID- 16969514
TI  - Allelic loss of Hox11L1 gene locus predicts outcome of gastrointestinal stromal
      tumors.
AB  - Loss of heterozygosity (LOH) in tumors has been described to have prognostic
      impact. Hox11L1 gene, located on chromosome 2, has a role in proliferation of
      neuronal myenteric Cajal cells being the progenitor cells of GISTs. The aim was
      to examine the frequency and prognostic value of allelic loss of Hox11L1 gene
      locus in GISTs. Tumor and control DNA of 72 GIST patients was extracted after
      microdissection from tissue sections. Patients underwent surgery between 1992 and
      2003 and were histopathologically reclassified. Microsatellite marker D2S286 on
      chromosomes 2 near Hox11L1 gene locus was used for detection of LOH by PCR and
      capillary electrophoresis. Survival was calculated by Kaplan-Meier plots. LOH was
      found in 7 (10%) of 72 GISTs. Fifty-four (75%) cases did not show LOH. Eleven
      (15%) were homozygous and consequently non-informative. Survival analysis (n=59)
      revealed a significantly worse tumor-specific and relapse-free survival for GIST
      patients with LOH in the tumor by univariate analysis (p<0.05 by log-rank test;
      median follow-up time 37 months). LOH of Hox11L1 gene locus is a useful parameter
      for prognosis of GIST. The data propose that Hox11L1 has a role in tumorigenesis
      in GISTs.

PMID- 16969515
TI  - Inhibitory effect of ailanthoidol on 12-O-tetradecanoyl-phorbol-13-acetate
      induced tumor promotion in mouse skin.
AB  - Many components derived from dietary or medicinal plants showing antioxidant and
      anti-inflammatory potential have been found to possess chemopreventive
      properties. In our previous study, we achieved the total synthesis of
      ailanthoidol (AT), a neolignan from Zanthoxylum ailanthoides or Salvia
      miltiorrhiza Bunge, which are used in Chinese traditional herbal medicine. In the
      present study, preliminarily, AT exhibited a radical quenching property by DPPH
      assay. Following this, we assessed the effect of AT on 12-O-tetradecanoylphorbol
      13-acetate (TPA)-induced oxidative stress and inflammation in female CD-1 mouse
      skin which was closely linked to tumor promotion. The topical application of AT
      (0.5-2.5 mM; 200 microl) reduced the formation of hydrogen peroxide and inhibited
      the myeloperoxidase (MPO) activity in the mouse skin when compared with that of
      the TPA-treated alone group. In addition, AT presented a suppression effect on
      the TPA-induced hyperplasia and leukocyte infiltration in the epidermis and edema
      of mouse ears. Furthermore, it showed that AT inhibited the TPA-induced
      expression of COX-2 protein and ornithine decarboxylase (ODC) activity in
      epidermis. Finally, AT was evaluated for its ability to inhibit the TPA-induced
      promotion in skin tumors of female CD-1 mice. Topical application of AT 5 min
      prior to TPA (5 nmol) three times weekly for 12 weeks to mice which were
      initiated with benzo[a]pyrene (B[a]P) inhibited the incidence of skin tumors in
      mice and the average number of tumors per mice as compared to TPA-treated alone.
      These results indicate that AT possesses potential as a chemopreventive agent
      against tumor promotion.

PMID- 16969516
TI  - Metastasis-associated protein 1 enhances angiogenesis by stabilization of HIF
      1alpha.
AB  - Metastasis-associated protein 1 (MTA1) is highly upregulated in cancer cells with
      metastatic potential; however, the molecular mechanism by which MTA1 increases
      the metastatic potential of cancer cells is unknown. We characterized the
      functional consequences of MTA1 overexpression in cancer cells with an emphasis
      on its potential role as a deacetylator of hypoxia-inducible factor-1alpha (HIF
      1alpha). MTA1 increased the expression of HIF-1alpha protein, but did not
      increase the expression of its mRNA. Glutathione S-transferase pull-down and
      coimmunoprecipitation assays demonstrated direct interaction of MTA1 with HIF
      1alpha both in vitro and in vivo. Immunoprecipitation and acetylation assays also
      showed that MTA1 has deacetylation activity on HIF-1alpha in vivo. Moreover, MTA1
      increased the transcriptional activity of HIF-1alpha and enhanced the expression
      of vascular endothelial growth factor, a target molecule of HIF-1alpha.
      Conditioned medium collected from MTA1 transfectants also increased angiogenesis
      in vitro and in vivo, probably through enhanced HIF-1alpha stabilization. These
      results indicate that MTA1 enhances angiogenesis by stabilization of the HIF
      1alpha protein, which is closely related to the increased metastatic potential of
      cancer cells with high MTA1 expression.

PMID- 16969567
TI  - [Non small cell lung cancer - comparison between clinical and pathological
      staging].
AB  - Lung cancer (LC) staging remains a clinical challenge as it determines the
      disease's prognosis and treatment. Surgery is the best option for controlling non
      small cell lung cancer (NSCLC) and the only potential cure. In this setting, lung
      cancer staging helps select patients who will benefit from surgery, excluding
      inoperable patients and including patients with resectable lesions. The aim of
      this study is to compare clinical staging (TNMc) with pathological staging (TNMp)
      and to evaluate diagnosis, complementary treatment and survival of these
      patients. This is a retrospective study that included patients with non-small
      cell lung cancer or with highly suspicious lesions who had undergone surgery and
      were followed up in the Hospital de Sao Joao lung cancer unit between January
      1999 and December 2003. It is based on clinical files and pathology reports.
      73.3% of this group of 60 patients were male, with median age 59.2 years. The
      most frequent TNMc stages were 41.7% T1N0M0 and 36.7% T2N0M0. Thoracotomy for
      therapeutic purpose was per- formed in 80% and thoracotomy for diagnostic purpose
      also in the remaining 20%. In 6.7% the resection was incomplete. The most
      frequent TNMp stages were T2N0p in 33.3%, T2N1p in 15.0% and T2N2p in 13.3%.
      There was a significant difference between the two staging types, with upstaging
      in 65.0%, down staging in 67% and only 28.3% keeping the same stage. The most
      frequent differences were from T1N0c to T2N0p and from T2N0c to T2N1p. The global
      agreement between both staging methods was 21.7%. Median global survival was 43
      months. In conclusion, while clinical staging was less accurate, it did not
      determine important changes in therapeutic strategy and survival. For the future,
      we should consider using other diagnostic tools and other biological factors to
      complement the anatomical information that we currently use.

PMID- 16969568
TI  - [The proliferative cytokines TGF-beta and VEGF in pleural effusions post-coronary
      artery bypass graft].
AB  - Coronary artery bypass graft (CABG) surgeries can impact on the pericardium and
      pleural space, leading to inflammation which can cause effusion. AIM: To study
      the role of the proliferative cytokines TGF-beta and VEGF in the fluids of 16
      transudates and 43 pleural effusions of patients who underwent CABG at the Heart
      Unit and Pulmonology Unit of the University Hospital of Sao Paulo. Levels of
      cytokines were assessed 2, 24 and 48 hours post-surgery. RESULTS: The pleural
      effusion after CABG is an exsudative mobilizer of TGF-beta and VEGF cytokines
      immediately after surgery. The TGF-beta concentrations were elevated 2 hours
      after surgery but started to fall soon after, reaching transudate levels after 48
      hours. VEGF levels were high in the first 2 hours post surgery and tended to
      maintain the same concentrations for at least 48 hours after surgery.
      CONCLUSIONS: Based on the results obtained, TGF-beta is a cytokine that seems to
      work as a trigger, leading the pleural mesothelial cell to express VEGF a cause
      of pleural effusion in CABG surgeries.

PMID- 16969569
TI  - Abnormal respiratory drive in vibroacoustic disease.
AB  - INTRODUCTION: Central nervous system disorders in workers exposed to low
      frequency noise (LFN, < 500 Hz, including infrasound) were first observed 25
      years ago among aircraft technicians. Concurrently, respiratory pathology was
      identified in these workers, and later reproduced in LFN-exposed animal models.
      Today vibroacoustic disease (VAD) is defined as the systemic pathology caused by
      excessive exposure to LFN. The respiratory tract continues to be under heavy
      scrutiny in both LFN-exposed humans and animal models and has been confirmed as a
      major target for LFN-induced damage. Given that both the respiratory and central
      nervous systems were compromised in these workers, it became pertinent to
      investigate the status of the neurological control of breathing in VAD patients.
      METHODS: The P- 0.1 value, a measure of the suction pressure developed at the
      mouth 0.1 seconds after the start of inspiration, depends on the respiratory
      centres and the autonomic nervous system pathway of the neural control of
      respiratory function. By rebreathing CO2, (6% in air) normal individuals present
      an average seven-fold increase in P0.1 (CO2) as compared to basal P- 0.1. Twenty
      two male VAD patients (ave. age 50.5 +/- 8.5 years, range: 36-66 years) underwent
      the P0.1(CO2) index respiratory drive tests, as well as standard pulmonary
      function tests. Seven individuals (ave. age 42.4 +/-14 years, range: 25- 61
      years) with reduced LFN exposure served as controls. RESULTS: Pulmonary function
      tests were normal in both VAD patients and controls. The P0.1 (CO2) in- dex was
      below average value in VAD patients (average: 22.9%) while it presented normal
      values in the control group (average > 60%). DISCUSSION: In the involuntary
      response to increased PCO2 levels, central chemoreceptors are responsible for 70%
      of the ventilatory stimulus. In VAD patients, this dysfunction may originate in
      the brainstem. This is corroborated by the fact that VAD patients register
      abnormal values for auditory brainstem evoked potentials, and disclose lesions
      with magnetic resonance imaging. The neurological control of breathing is
      compromised in VAD patients. The P0.1 (CO2) index may be a useful clinical
      indicator for VAD diagnosis and follow-up.

PMID- 16969570
TI  - Voice acoustic patterns of patients diagnosed with vibroacoustic disease.
AB  - BACKGROUND: Long-term low frequency noise exposure (LFN) (< or = 500 Hz,
      including infrasound) may lead to the development of vibroacoustic disease (VAD),
      a systemic pathology characterized by the abnormal growth of extra-cellular
      matrices. The respiratory system is a target for LFN. Fibrosis of the respiratory
      tract epithelia was observed in VAD patients through biopsy, and confirmed in
      animal models exposed to LFN. Voice acoustic analysis can detect vocal fold
      variations of mass, tension, muscular and neural activity. Frequency perturbation
      (jitter), amplitude perturbation (shimmer) and harmonic-to-noise ratio (HNR) are
      used in the evaluation of the vocal function, and can be indicators of the
      presence and degree of severity of vocal pathology. Since the respiratory system
      is the energy source of the phonation process, this raises questions about the
      effects of VAD on voice production. The purpose of this study was to determine if
      voice acoustic parameters of VAD patients are different from normative data.
      METHODS: Nine individuals (5 males and 4 females) diagnosed with VAD were
      recorded performing spoken and sung tasks. The spoken tasks included sustaining
      vowels and fricatives. The sung tasks consisted of maximum phonational frequency
      range (MPFR). Voice acoustic parameters ana- lysed were: fundamental frequency
      (F0), jitter, shimmer, HNR and temporal measures. RESULTS: Compared with
      normative data, both males and females diagnosed with VAD exhibited increased F0,
      shimmer and HNR. Jitter, MPFR and one temporal measure were reduced. CONCLUSIONS:
      VAD individuals presented voice acoustic parameter differences in spectral,
      temporal and perturbation measures, which may be indicative of small
      morphological changes in the phonatory system.

PMID- 16969571
TI  - [Pulmonary arteriovenous malformations - association with hereditary hemorrhagic
      telangiectasia. Clinical cases and family screening].
AB  - Pulmonary arteriovenous malformations are a rare disorder associated to
      hereditary hemorrhagic telangiectasia in over 50 % of the cases. Clinical
      presentation, diagnostic work-up, therapeutic options and prognosis are reviewed
      by the authors. Pulmonary arteriovenous malformations are known to have
      considerable morbidity and mortality, their treatment being advisable as well as
      their screening among family members, especially if the index case is diagnosed
      with both pulmonary arteriovenous malformations and hereditary hemorrhagic
      telangiectasia. To this moment prospective studies establishing the best
      diagnostic work-up for the patients and their families are lacking. The authors
      report two pulmonary arteriovenous malformations cases in a family with
      hereditary hemorrhagic telangiectasia. Patient's diagnosis led to family
      screening which resulted in the identification of pulmonary arteriovenous
      malformations in two family members and pulmonary disease exclusion in four
      patients previously known to have hereditary hemorrhagic telangiectasia.

PMID- 16969572
TI  - [Historic landmarks in the study of lung cancer].
AB  - This study reviews the milestones which have been reached in the study of lung
      cancer, from its first early descriptions up until the end of the twentieth
      century. The study accompanies the birth of this new clinical entity, underlining
      the difficulties inherent in its diagnosis, its ever-growing increase and traces
      the growth of its aetiological factors, placing particular emphasis on smoking.
      In tandem with this, the study delves into the clinical aspects, along with new
      discoveries in imaging techniques and endoscopic and bioscopic techniques. It
      also looks at the histopathological classifications of bronchopulmonary tumours
      and the various staging systems which have been used over the course of time as
      well as the importance of mapping the disease and the different treatment weapons
      which have successively become available in the fight against it. The study also
      takes a look at the scales used in evaluating patients' physiological condition,
      the criteria used in evaluating response to oncostatic treatment and the role
      some international and national scientific societies and medical associations
      have played in adding to the increasing medical knowledge of lung cancer. The
      study clearly shows to whom we are indebted for each advance. This is a
      fascinating sweep of history - as is the story of all medical progress - and one
      we feel is important to understand, in order for us to see more clearly where we
      are now.

PMID- 16969573
TI  - [Simple methods for estimating the concentration of toxic pollutants inside
      buildings].
AB  - This paper presents simple methods for determining the concentration of toxic
      substances inside buildings, due to immediate release. Some case stu- dies are
      also presented, showing that these methods could go towards solving typical
      problems involved in building ventilation, such as the quantification of the
      number of air renovations necessary to exhaust toxic gases from inside buildings
      or to avoid the contamination by toxic gases coming from outside.

PMID- 16969574
TI  - [Epithelioid haemangioendothelioma of the pleura: 29 months survival].
AB  - Epithelioid haemangioendothelioma of the pleura is a rare neoplasia with a very
      poor prognosis due to aggressive involvement of the pleura and incomplete
      surgical treatment. Histological diagnosis and imagiology is also controversial,
      related to discrete development of the lesions that later reveal nodules. In 2005
      there were 31 cases of vascular tumours described in the pleura. Eleven were
      epithelioid haemangioendotheliomas. This is another case, a 52 year old woman who
      suffered a traumatism and died 29 months after the histological diagnosis because
      CAT revealed discrete pleural involvement and a 2 cm nodule was seen only one
      month before death.

PMID- 16969575
TI  - [Endobronchial granular cell tumor - what approach to take].
AB  - Granular cell tumor is a mesenchymal neoplasm almost always benign, with tendency
      to recurrence. Although it is more frequent in in the head and neck it has been
      described in almost all areas of the body. Its occurrence in the lung is
      extremely rare. The authors describe two cases of endobronchial granular cell
      tumours, discuss the particularities of this pathology as well as the treatment
      options, with particular attention to the use of endobronchial excision and
      criotherapy.

PMID- 16969576
TI  - [Ehlers-Danlos syndrome - a rare cause of spontaneous pneumothorax].
AB  - Ehlers-Danlos syndrome (cutis hyperelastica), is a group of connective tissue
      disorders characterized by abnormalities of the skin, ligaments and internal
      organs. It is a hereditary syndrome, usually with autossomal dominant
      inheritance; that primarily affects the collagen synthesis. The skin and blood
      vessels are extremely fragile and elastic. The skin is soft with rubber
      consistency and easily bruising. There are hypermobile joints with increased
      extensibility. We summarize the case of a sixteen year old boy with a history of
      joint hypermobility since childhood and splenic fracture that was diagnosed with
      Ehlers-Danlos syndrome after the occurrence of recidivant spontaneous
      pneumothorax. We present the most common pulmonary complications of Ehlers-Danlos
      syndrome and discuss the importance of not forgetting the least commons
      etiologies of pneumothorax, in cases of spontaneous pneumothorax.

PMID- 16969577
TI  - Stability analysis of paraplegic standing while wearing an orthosis.
AB  - Paraplegics can maintain a standing posture, called the "C-posture", while
      wearing an orthosis. The significant feature of the C-posture is that the body's
      center of mass is located behind the hip joint. In this study, we investigate the
      C-posture mechanism and assess the relationship between posture and stability,
      the aim being to restore standing function. We first measured the standing
      postures of paraplegic subjects wearing an orthosis. The subjects maintained the
      standing posture for 30 s. Next, assuming the C-posture to be an equilibrium
      attractor in the musculoskeletal system, we used a dynamic model of the
      musculoskeletal system to analyze the relationship between posture and stability,
      and also to assess the influence of ankle stiffness. We calculated the standing
      posture on the basis of a return map. The calculated standing postures show some
      features of the C-posture. The stability analysis revealed that, despite a
      limitation in the range of stable postures, the C-posture is more stable than the
      postures of normal people. The results suggest that although the C-posture is an
      appropriate posture for paraplegic standing, sufficient ankle stiffness and an
      appropriate alignment of ankle angle are necessary and preventing hip flexion
      movements is desirable.

PMID- 16969578
TI  - Comment to the article "Impaction allograft with cement for the revision of the
      femoral component. A minimum 39-month follow-up study (SJ Yim et al.)".

PMID- 16969579
TI  - Comparison of the degenerative changes in weight-bearing joints following
      cementing or grafting techniques in giant cell tumour patients: medium-term
      results.
AB  - The aim of this retrospective study was to compare and assess the effect of bone
      grafting and cementing techniques--two common applications used in the treatment
      of subchondral giant cell tumours of bone (GCTs)--on the development of
      degenerative changes in the weight-bearing joints of the lower extremity. Eighty
      patients were included in this follow-up study, 44 of whom underwent curettage
      followed by bone grafting, and 36 who had curettage followed by cementation. At
      the 24-month post-operative examination, significantly less degenerative change
      was found in patients with bone cement than in those with bone grafting. At the
      50-month and later (range: 50-148 months) post-operative examination, however, no
      significant differences were found between the two groups, indicating that there
      was a significant acceleration of degenerative changes in the cemented group
      after the 24-month follow-up.

PMID- 16969580
TI  - Treatment with antidepressant medications in private health plans.
AB  - This study analyzed 2002 MarketScan data from a convenience sample of enrollees
      with private health insurance from the largest U.S. firms to examine utilization,
      expenditures, and factors associated with antidepressant prescriptions. Of
      enrollees, 11% received at least one antidepressant prescription during the year
      with average expenditures per enrollee of $51.55. Antidepressant prescriptions
      were more frequently used than any form of other mental health care and for 42%
      of users was not associated with any clearly identified mental health or "off
      label" indication. In logistical regression analyses, health plan type,
      prescription days supply, gender, region, age, employment status, and subscriber
      status were associated with unexplained antidepressant prescription use.

PMID- 16969581
TI  - Analyses of the associations between the genes of 22q11 deletion syndrome and
      schizophrenia.
AB  - Schizophrenia is a severe, debilitating mental disorder characterized by profound
      disturbances of cognition, emotion and social functioning. The lifetime morbid
      risk is surprisingly uniform at slightly less than 1% across different
      populations and different cultures. The evidence of genetic risk factors is our
      strongest clue to the cause of schizophrenia. Linkage and association analyses
      have identified genes associated with the development of schizophrenia. However,
      most of the alleles or haplotypes identified thus far have only a weak
      association or are reported to be population specific. A deletion of 22q11.2 that
      causes the most common microdeletion syndrome (22q11DS) with an estimated
      prevalence of 1:2,500-1:4,000 live births may represent one of the greatest known
      genetic risk factors for schizophrenia. Schizophrenia is a late manifestation in
      approximately 30% of patients with 22q11.2 deletion, comparable to the risk to
      offspring of two parents with schizophrenia. Clinical and neuroimaging
      assessments indicate that 22q11DS-schizophrenia is a neurodevelopmental model of
      schizophrenia. Recent studies have provided evidence that haploinsufficiency of
      TBX1 is likely to be responsible for many of the physical features associated
      with the deletion. Most of the genes in the 22q11 deletion region are conserved
      together on mouse chromosome 16, enabling the generation of mouse models.
      Similarities in the cardiovascular and other phenotypes between 22q11DS patients
      and mouse models can provide important insights into roles of genes in
      neurobehavioral phenotypes. Because more than one gene in the 22q11DS region is
      likely to contribute to the marked risk for schizophrenia, further extensive
      studies are necessary. Analyses of 22q11DS will help clarify the molecular
      pathogenesis of schizophrenia.

PMID- 16969582
TI  - The genetic and molecular basis of muscular dystrophy: roles of cell-matrix
      linkage in the pathogenesis.
AB  - Muscular dystrophies are a heterogeneous group of genetic disorders. In addition
      to genetic information, a combination of various approaches such as the use of
      genetic animal models, muscle cell biology, and biochemistry has contributed to
      improving the understanding of the molecular basis of muscular dystrophy's
      etiology. Several lines of evidence confirm that the structural linkage between
      the muscle extracellular matrix and the cytoskeleton is crucial to prevent the
      progression of muscular dystrophy. The dystrophin-glycoprotein complex links the
      extracellular matrix to the cytoskeleton, and mutations in the component of this
      complex cause Duchenne-type or limb-girdle-type muscular dystrophy. Mutations in
      laminin or collagen VI, muscle matrix proteins, are known to cause a congenital
      type of muscular dystrophy. Moreover, it is not only the primary genetic defects
      in the structural or matrix proteins, but also the primary mutations of enzymes
      involved in the protein glycosylation pathway that are now recognized to disrupt
      the matrix-cell interaction in a certain group of muscular dystrophies. This
      group of diseases is caused by the secondary functional defects of dystroglycan,
      a transmembrane matrix receptor. This review considers recent advances in
      understanding the molecular pathogenesis of muscular dystrophies that can be
      caused by the disruption of the cell-matrix linkage.

PMID- 16969583
TI  - GGN repeat length and GGN/CAG haplotype variations in the androgen receptor gene
      and prostate cancer risk in south Indian men.
AB  - The ethnic variation in the GGN and CAG microsatellites of the androgen receptor
      (AR) gene suggests their role in the substantial racial difference in prostate
      cancer risk. Hence, we performed a case-control study to assess whether GGN
      repeats independently or in combination with CAG repeats were associated with
      prostate cancer risk in South Indian men. The repeat lengths of the AR gene
      determined by Gene scan analysis, revealed that men with GGN repeats <or=21 had
      no significant risk compared to those with >21 repeats (OR 0.91 at 95% CI-0.52
      1.58). However, when CAG repeats of our earlier study was combined with the GGN
      repeat data, the cases exhibited significantly higher frequency of the haplotypes
      CAG <or=19/GGN <or=21 (OR-5.2 at 95% CI-2.17-12.48, P < 0.001) and CAG <or=19/GGN
      > 21(OR-6.9 at 95%CI-2.85-17.01, P < 0.001) compared to the controls. No
      significant association was observed between GGN repeats and prostate-specific
      antigen levels and the age at diagnosis. Although a trend of short GGN repeats
      length in high-grade was observed, it was not significant (P = 0.09). Overall,
      our data reveals that specific GGN/CAG haplotypes (CAG <or=19/GGN <or=21 and CAG
      <or=19/GGN > 21) of AR gene increase the risk of prostate cancer and thus could
      serve as susceptibility marker for prostate cancer in South Indian men.

PMID- 16969584
TI  - Visual search for orientation of faces by a chimpanzee (Pan troglodytes): face
      specific upright superiority and the role of facial configural properties.
AB  - A previous experiment showed that a chimpanzee performed better in searching for
      a target human face that differed in orientation from distractors when the target
      had an upright orientation than when targets had inverted or horizontal
      orientation [Tomonaga (1999a) Primate Res 15:215-229]. This upright superiority
      effect was also seen when using chimpanzee faces as targets but not when using
      photographs of a house. The present study sought to extend these results and
      explore factors affecting the face-specific upright superiority effect. Upright
      superiority was shown in a visual search for orientation when caricaturized human
      faces and dog faces were used as stimuli for the chimpanzee but not when shapes
      of a hand and chairs were presented. Thus, the configural properties of facial
      features, which cause an inversion effect in face recognition in humans and
      chimpanzees, were thought to be a source of the upright superiority effect in the
      visual search process. To examine this possibility, various stimuli manipulations
      were introduced in subsequent experiments. The results clearly show that the
      configuration of facial features plays a critical role in the upright superiority
      effect, and strongly suggest similarity in face processing in humans and
      chimpanzees.

PMID- 16969585
TI  - Solution structure and phosphopeptide binding of the SH2 domain from the human
      Bruton's tyrosine kinase.

PMID- 16969586
TI  - Dislocation of three segments of the liver due to hernia of the right diaphragm:
      report of a case and review of the literature.
AB  - Right diaphragmatic hernia is a rare injury (0.25-1%) following blunt abdominal
      trauma. The diagnosis may be delayed and achieved years after the trauma during
      laparotomies for other reasons. A 75-year-old male fell 6 years before, and was
      symptom-free since then. He was admitted to the hospital for abdominal pain, and
      chest X-rays revealed intestinal gas in the lower right thoracal region.
      Abdominal ultrasonography showed agenesis of the gallbladder, and computed
      tomography demonstrated that the right upper abdominal viscera were located in
      the vicinity of the heart. The patient underwent a laparotomy for right
      diaphragmatic hernia, and the right hepatic lobe and the medial segment of the
      left lobe, the gall bladder, the proximal part of the transverse colon, the
      omentum and some segments of the intestine were dislocated into the thoracal
      cavity by a tear in the right diaphragm. The organs were returned to the
      abdominal cavity uneventfully and the defect in the diaphragm, measuring 10 x 5
      cm, was repaired by unabsorbable sutures. The diagnosis, surgical treatment and
      postoperative course of the right diaphragmatic hernia is discussed with a review
      of the literature.

PMID- 16969587
TI  - The new 4DDome prosthesis: an original light and partially absorbable composite
      mesh for hernia repair.
AB  - INTRODUCTION: The use of non-absorbable meshes for the repair of inguinal hernias
      has become standard; however, these meshes have been associated with
      complications including long-term postoperative pain. To this end, a new
      partially absorbable composite mesh has been developed, and the aim of this study
      was to investigate its efficacy in animal and human trials. MATERIALS AND
      METHODS: Sixty male Wistar rats were used to evaluate the behavior of the newly
      designed composite mesh. Composite meshes were implanted in the extra-peritoneal
      plane for 2, 4 and 8 weeks and compared to a standard polypropylene mesh. Forty
      patients with symptomatic inguinal hernias were treated using a new 4DDome
      designed prosthesis. Follow-up was by clinical and ultrasound examination at 1, 6
      and 12 months. RESULTS: The animal study demonstrated that the inflammatory
      reaction associated with the new composite mesh was significantly lower than a
      standard polypropylene mesh, characterized by a lower macrophage infiltrate (P <
      0.001). The mesh did not shrink over the 8-week period, unlike the polypropylene
      mesh (P < 0.05). The human study showed that there were three minor postoperative
      complications, no recurrences and the mesh was well tolerated. Follow-up with
      serial ultrasound showed that at 10 days and 1 month the dome was clearly visible
      in position; however, by 6 months it had flattened out, been partially absorbed
      and become incorporated into the repair. CONCLUSION: These experimental and
      clinical studies have validated the concept of the new 4DDome composite mesh. It
      was well tolerated and was associated with good short-term results. The
      combination of the dome shape and the new composite mesh means that less
      polypropylene is required and represents a significant advance in anterior hernia
      repair.

PMID- 16969588
TI  - Change in lean body mass is a major determinant of change in areal bone mineral
      density of the proximal femur: a 12-year observational study.
AB  - Our objective was to assess the contribution of lean body mass (LBM) and fat body
      mass (FBM) to areal bone mineral density (aBMD) in women during the years
      surrounding menopause. We used a 12-year observational design. Participants
      included 75 Caucasian women who were premenopausal, 53 of whom were available for
      follow-up. There were two measurement periods: baseline and 12-year follow-up. At
      both measurement periods, bone mineral content and aBMD of the proximal femur,
      posterior-anterior lumbar spine, and total body was assessed using dual-energy X
      ray absorptiometry (DXA). LBM and FBM were derived from the total-body scans.
      General health, including current menopausal status, hormone replace therapy use,
      medication use, and physical activity, was assessed by questionnaires. At the end
      of the study, 44% of the women were postmenopausal. After controlling for
      baseline aBMD, current menopausal status, and current hormone replacement
      therapy, we found that change in LBM was independently associated with change in
      aBMD of the proximal femur (P = 0.001). The cross-sectional analyses also
      indicated that LBM was a significant determinant of aBMD of all three DXA-scanned
      sites at both baseline and follow-up. These novel longitudinal data highlight the
      important contribution of LBM to the maintenance of proximal femur bone mass at a
      key time in women's life span, the years surrounding menopause.

PMID- 16969589
TI  - Runx2 overexpression enhances osteoblastic differentiation and mineralization in
      adipose--derived stem cells in vitro and in vivo.
AB  - Like bone marrow stromal cells, adipose tissue-derived stem cells (ADSCs) possess
      multilineage potential, a capacity for self-renewal and long-term viability. To
      confirm whether ADSCs represent a promising source of cells for gene-enhanced
      bone tissue-engineering, the osteogenic potential of ADSCs under the control of
      certain osteoinductive genes has been evaluated. Runx2, a transcription factor at
      the downstream end of bone morphogenetic protein (BMP) signaling pathways, is
      essential for osteoblast differentiation and bone formation. In this study we
      used adenovirus vector to deliver Runx2 to ADSCs and then examined the
      enhancement of osteogenic activity. Overexpression of Runx2 inhibited
      adipogenesis, as demonstrated by suppression of LPL and PPARgamma expression at
      the mRNA level and reduced lipid droplet formation. Moreover, ADSCs transduced
      with Ad-Runx2 underwent rapid and marked osteoblast differentiation as determined
      by osteoblastic gene expression, alkaline phosphatase activity and mineral
      deposition. Additionally, histological examination revealed that implantation of
      Runx2 modified ADSCs could induce mineral deposition and bone-like tissue
      formation in vivo. These results confirmed, firstly, the ability of Runx2 to
      promote osteogenesis and cell differentiation and, secondly, the competence of
      ADSCs as target cells for bone tissue engineering. Our work demonstrates a
      potential new approach for bone repair using Runx2-modified ADSCs for bone tissue
      engineering.

PMID- 16969590
TI  - SULT1E1 genetic polymorphisms modified the association between phytoestrogen
      consumption and bone mineral density in healthy Korean women.
AB  - Sulfotransferase 1E1 (SULT1E1) catalyze estrogen into sulfate conjugation and is
      involved in the metabolism of phytoestrogen. A community-based cross-sectional
      study was conducted on 397 Korean women, to evaluate the association between
      genetic polymorphisms of SULT1E1 and bone mineral density (BMD) and the combined
      effect of the genetic polymorphism and phytoestrogen intake for BMD in Korean
      women. BMDs of the distal radius and the calcaneus were measured by dual-energy X
      ray absorptiometry. Genotypes of SULT1E1 IVS1-447 C>A, IVS4-1653 T>C, and *959
      G>A were determined by the 5'-nuclease assay (TaqMan). Phytoestrogen intake was
      estimated by a food-frequency questionnaire validated against multiple 24-hour
      recalls. Women with the SULT1E1 *959 GG genotype had a 4.5% lower BMD at the
      distal radius (P (trend )= 0.05) and a 7.9% lower BMD at the calcaneus compared
      to those with AA genotype (P (trend) < 0.01), whereas the SULT1E1 IVS1-447 CC
      genotype and IVS4-1653 TT genotype were not associated with BMD. There was no
      significant trend of BMD with the numbers of CTG-containing haplotypes, but
      calcaneal BMDs significantly differed between SULT1E1 CTA-CTA haplotype and CTG
      CCA haplotype (P < 0.05). When stratified by SULT1E1 genotype, the correlation
      between phytoestrogen consumption and BMD at the calcaneus was noteworthy in
      women with SULT1E1 *959 GG genotype (r = 0.25, P = 0.01) or SULT1E1 IVS 4-1653 TT
      genotype (r = 0.15, P = 0.02). This trend remained significant only in
      postmenopausal women (r = 0.36, P = 0.01) after multiple testing was corrected by
      the false discovery rate method. In conclusion, the genetic polymorphism of
      SULT1E1 *959 G > A was associated with BMD at the distal radius and calcaneus,
      and the association between phytoestrogen consumption and calcaneal BMD might be
      modified by this genetic polymorphism.

PMID- 16969591
TI  - Degree of mineralization-related collagen crosslinking in the femoral neck
      cancellous bone in cases of hip fracture and controls.
AB  - Based on the present definition of osteoporosis, both bone density and quality
      are important factors in the determination of bone strength. Collagen
      crosslinking is a determinant of bone quality. Cross-links can form enzymatically
      by the action of lysyl oxidase or non-enzymatically, resulting in advanced
      glycation end products. Collagen crosslinking is affected by tissue maturation as
      well as the degree of mineralization. Homocysteine and vitamin B6 (pyridoxal) are
      also regulatory factors of collagen crosslinking. We elucidate the relationship
      between the degree of mineralization and collagen cross-links in cancellous bone
      from hip fracture cases. We also determined plasma levels of homocysteine and
      pyridoxal. Twenty-five female intracapsular hip fracture cases (78 +/- 6 years)
      and 25 age-matched postmortem controls (77 +/- 6 years) were included in this
      study. Collagen crosslinking was analyzed after each bone specimen was
      fractionated into low (1.7-2.0 g/ml) and high (>2.0 g/ml) density fractions. The
      content of enzymatic (immature reducible and mature nonreducible cross-links) and
      nonenzymatic cross-link (pentosidine) were determined. In the controls, there was
      no difference in total enzymatic cross-links between low and high density bone,
      while pentosidine content was significantly higher in high density bone. In the
      fracture cases, not only reduced enzymatic cross-links in high density bone and
      increased pentosidine in both low and high density bone, but also higher plasma
      homocysteine and lower pyridoxal levels were evident compared with the controls.
      These results indicate that detrimental crosslinking in both low and high
      mineralized bone result in impaired bone quality in osteoporotic patients.

PMID- 16969592
TI  - A randomized, double-blind, placebo-controlled trial of intravenous zoledronic
      acid in the treatment of thalassemia-associated osteopenia.
AB  - Beta-thalassaemia major is associated with low bone mass and fractures. We
      conducted a 2 year randomized controlled trial of zoledronic acid 4 mg
      administered intravenously every 3 months or placebo in the treatment of beta
      thalassaemia-associated osteopenla. We recruited 23 subjects from 2 university
      hospitals with a T score of less than -1.0 at either the lumbar spine or hip, and
      23 subjects completed the study (17 M, 6 F). Treatment groups did not differ
      significantly with respect to bone mineral density (BMD), age, height, weight and
      body mass index (BMI) at baseline. BMD was assessed at baseline, 12 months and 24
      months by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, femoral
      reek, total hip and total body. After two years average lumbar spine BMD was 8.9%
      greater (95%CI 2.3-15.5%, P = 0.011), average femoral neck BMD was 9.1% greater
      (95%CI 5.5-12.7%, P < 0.0001), average total hip BMD was 9.6% greater (95%CI 6.5
      12.6%, P < 0.0001) and average total body BMD was 4.7% greater (95%CI 2.7-6.8%, P
      < 0.0001) in the treated group compared to placebo. The absolute change in BMD
      from baseline to 2 years and the annualized rate of change of BMD was
      significantly greater in treated patients at all four sites. Age, gender, height,
      weight and BMI did not interact with the effect of treatment and so unadjusted
      data was used. The serum total ALP decreased 45% by 12 months (P = 0.004) and
      urinary deoxypyridinoline/creatinine ratio decreased 47% by 3 months (NS). We
      conclude that zoledronic acid (4 mg i.v. 3 monthly) suppresses bone turnover and
      increases BMD in beta-thalassaemia-associated osteopenia.

PMID- 16969593
TI  - The pathogenesis, epidemiology and management of glucocorticoid-induced
      osteoporosis.
AB  - Oral glucocorticoids (GCs) are frequently used in the treatment of inflammatory
      conditions, such as rheumatoid arthritis or asthma. They have adverse skeletal
      effects, primarily through reductions in bone formation and osteocyte apoptosis.
      Several findings indicate that changes in the quality of bone may significantly
      contribute to the increased risk of fracture and that loss of BMD only partially
      explains the increased risk of fracture in oral GC users. Epidemiological studies
      have found that the increases in the risk of fracture in oral GC users are dose
      dependent and occur within three months of starting GC therapy. Daily doses of
      >2.5 mg prednisone equivalent have been associated with increases in the risk of
      fractures and randomised studies reported adverse skeletal effects with daily
      doses as low as 5 mg. After discontinuation of GC treatment, the risk of fracture
      may reduce towards baseline levels unless patients previously used high
      cumulative doses of oral GCs. Users of inhaled GCs have also an increased risk of
      fracture, especially at higher doses. But it is likely that this excess risk is
      related to the severity of the underlying respiratory disease, rather than to the
      inhaled GC therapy. It has been recommended that patients who start on oral GC
      therapy should receive calcium and vitamin D supplementation. Patients with a
      higher risk of fracture should also receive a bisphosphonate.

PMID- 16969595
TI  - Degree and distribution of mineralization in the human mandibular condyle.
AB  - The degree of mineralization of bone (DMB) in the mandibular condyle reflects the
      age and remodeling rate of the bone tissue. Quantification of DMB facilitates a
      better understanding of possible effects of adaptive remodeling on mineralization
      of the condyle and its possible consequences for its mechanical quality. We
      hypothesized differences in the degree and distribution of mineralization between
      trabecular and cortical bone and between various cortical regions. Microcomputed
      tomography was used to measure mineralization in 10 human mandibular condyles.
      Mean DMB was higher in cortical (1,045 mg hydroxyapatite/cm(3)) than in
      trabecular bone (857 mg/cm(3)) and differed significantly between cortical
      regions (anterior 987 mg/cm(3), posterior 1,028 mg/cm(3), subchondral 1,120
      mg/cm(3)). The variation of DMB distribution was significantly larger in the
      anterior cortex than in the posterior and subchondral cortex, indicating a larger
      amount of heterogeneity of mineralization anteriorly. Within the cortical bone,
      DMB increased with the distance from the cortical canals to the periphery.
      Similarly, the DMB of trabecular bone increased with the distance from the
      surface of the trabeculae to their cores. It was concluded that the rate of
      remodeling differs between condylar trabecular and cortical bone and between
      cortical regions and that DMB is not randomly distributed across the bone. The
      difference in DMB between condylar cortical and trabecular bone suggests a large
      difference in Young's modulus.

PMID- 16969594
TI  - Site-specific in vivo calcification and osteogenesis stimulated by bone
      sialoprotein.
AB  - Bone sialoprotein (BSP) is one of the major non-collagenous glycosylated
      phosphoproteins of the extracellular matrix in bone. In vitro studies suggest
      that BSP may play important roles in the initiation and/or growth of calcium
      phosphate crystals. To investigate the potential role of BSP in more complex in
      vivo environments, we implanted purified bovine BSP with type-I collagen as a
      carrier into surgically created rat calvarial defects and thoracic subcutaneous
      pouches. The responses to the implants were assessed by histochemistry,
      immunohistochemistry, in situ hybridization, quantitative real-time PCR, and
      biochemical analyses. BSP-collagen, but not collagen alone, elicited mineral
      deposition in the matrix of proliferating cells near the dura at days 4-5
      followed by osteoblast differentiation and synthesis of new bone in the mid
      portion of the calvarial defects. In contrast, implantation of BSP-collagen into
      subcutaneous pouches did not induce calcification or osteogenesis over the same
      experimental period. We explored the underlying mechanisms for the site-specific
      responses to BSP-collagen implants and found that higher levels of calcium
      content and alkaline phosphatase activity at the cranial site at days 2-5 were
      associated with the BSP-mediated calcification. We also found that BSP stimulated
      osteoblast differentiation through up-regulation of cbfa1 and osterix, key
      transcription factors of osteoblast differentiation, which occurred in the
      calvarial defects but not in the subcutaneous tissue. These results demonstrate
      that BSP stimulates calcification and osteogenesis in a site-specific manner, and
      that local environment and the specificities of responding cells may play
      critical roles in the function of BSP in vivo.

PMID- 16969596
TI  - Daily treatment of aged ovariectomized rats with human parathyroid hormone (1-84)
      for 12 months reverses bone loss and enhances trabecular and cortical bone
      strength.
AB  - Most studies that have investigated the anabolic effects of parathyroid hormone
      (1-84) (PTH) or PTH fragments on the skeleton of ovariectomized (OVX) rats have
      evaluated the short-term effects of high-dose PTH(1-34) in young animals. This
      study used densitometry, histomorphometry, and biomechanical testing to evaluate
      the effects of 12-month daily treatment with low-dose PTH (15 or 30 microg/kg) in
      rats that were 10 months old at baseline, 4 months after OVX. Bone mineral
      density (BMD) and bone strength were reduced substantially in control OVX rats.
      The 15 microg/kg dose of PTH restored BMD to levels similar to those in sham
      animals within 6 months at the lumbar spine, distal and central femur, and whole
      body and maintained the BMD gain from 6 to 12 months. The 30 microg/kg dose
      produced greater effects. Both PTH doses normalized the trabecular bone volume-to
      total volume ratio (BV/TV) at lumbar vertebra 3 but not at the proximal tibia
      (where baseline BV/TV was very low), solely by increasing trabecular thickness.
      PTH dose-dependently increased bone formation by increasing the mineralizing
      surface, but only the 30 microg/kg dose increased resorption. PTH increased
      cortical BMD, area, and thickness, primarily by increasing endocortical bone
      formation, and restored all measures of bone strength to levels similar to those
      in sham animals at all skeletal sites. PTH increased bone mass safely; there was
      no osteoid accumulation, mineralization defect, or marrow fibrosis and there were
      no abnormal cells. Thus, long-term PTH therapy normalized bone strength in the
      aged OVX rat, a model of postmenopausal osteoporosis, through increased bone
      turnover and enhanced formation of both trabecular and cortical bone.

PMID- 16969598
TI  - Application of a triage approach to peripheral bone densitometry reduces the
      requirement for central DXA but is not cost effective.
AB  - A method proffered for the interpretation of measurements from peripheral dual
      energy X-ray absorptiometry (pDXA) is a triage approach to stratify patients into
      one of three risk categories; (i) high-treat, (ii) medium-refer for central DXA
      and (iii) low-reassure. The aim of this study was to apply the triage approach to
      measures from peripheral scanners and risk indices and stratify patients into one
      of three risk categories (i), (ii) or (iii). 207 post-menopausal women had
      central DXA from which they were categorised as non-osteoporotic or osteoporotic.
      Additional peripheral scans of the left calcaneus were performed on three
      scanners (GE Lunar Achilles and PIXI, McCue CubaClinical). From demographic
      details four risk indices were calculated and algorithms combining measures from
      peripheral scanners and one risk index were obtained. All peripheral measures,
      risk indices and combination algorithms were good at identifying women at risk of
      osteoporosis (ROC areas: 0.67-0.82). Each tool stratified varying numbers of
      osteoporotic and non-osteoporotic women into each risk category using the triage
      approach. One combination algorithm (PIXI & osteoporosis indices of risk
      (OSIRIS)) performed best by minimising misclassification (10% non-osteoporotic,
      10% osteoporotic) and reducing requirement for central DXA to 36%. However the
      cost of implementing the triage approach for PIXI & OSIRIS was greater (263%)
      than central DXA (100%) scanning all women. Although the triage approach was an
      effective tool at identifying women at risk of osteoporosis the unnecessary
      treatment of non-osteoporotic women in the high risk category make it
      impractical. Therefore an alternative more cost-effective method has been
      suggested.

PMID- 16969597
TI  - Calcaneus ultrasonometry and dual-energy X-ray absorptiometry for the evaluation
      of vertebral fracture risk.
AB  - The aim of this retrospective, cross-sectional, controlled, non-population-based
      study was to evaluate the specificity and sensitivity of quantitative
      ultrasonometry (QUS) of the heel and of dual-energy X-ray absorptiometry (DXA) in
      the prediction of morphometric vertebral fracture in postmenopausal women and to
      establish whether the combination of the two devices could improve the capacity
      to identify the presence of vertebral fracture. Also, we tried to identify the
      best T-score threshold for high risk of vertebral fracture for both QUS and DXA,
      highlighting the discrepancies between the two methodologies and between the
      various sites examined with DXA. From 6,300 patients examined by DXA (total body,
      lumbar spine, total femur, femoral neck), QUS and DXA vertebral morphometry
      (MXA), we selected 764 postmenopausal women with nontraumatic vertebral
      fractures; 770 postmenopausal women with normal morphometry were chosen as a
      control group. Logistic regression analysis yielded odds ratios (ORs) for bone
      mineral density (BMD) measurements and QUS that were comparable: BMD-total body
      4.16, BMD-lumbar spine 4.80, BMD-total femur 3.77, BMD-femoral neck 3.86, and QUS
      4.41, without statistical differences even after correction for different
      confounding variables (menopausal years, weight, height, body mass index, and
      age). The ORs obtained from different combinations of QUS and DXA results did not
      show statistically significant differences compared to those from a single method
      alone. The sensitivity and specificity of all measurements were determined by
      area using the receiver operating characteristic curve; these were 0.94 for total
      body, 0.95 for lumbar spine, 0.86 for total femur, 0.89 for femoral neck, and
      0.93 for QUS, without statistical difference. The areas under the curve obtained
      from the combination of QUS and DXA were higher but without statistical
      significance compared to QUS alone. In conclusion, both QUS and DXA were able to
      discriminate women with fracture from women without fracture and independently
      contributed to determining the association with fracture. The combination of QUS
      and BMD did not improve the diagnostic ability of either individual technique. We
      found different diagnostic thresholds for QUS and DXA.

PMID- 16969601
TI  - Comparison of routine and unprepped CT colonography augmented by low fiber diet
      and stool tagging: a pilot study.
AB  - BACKGROUND: We performed a pilot study examining the feasibility of a new
      unprepped CT colonography (CTC) strategy: low fiber diet and tagging (unprepped)
      vs. low fiber diet, tagging and a magnesium citrate cleansing preparation
      (prepped). Prior reports of tagging were limited in that the residual stool was
      neither measured and stratified by size nor did prior reports subjectively
      evaluate the ease of interpretation by a reader experienced in interpreting CTC
      examinations. METHODS: Prospective randomized to unprepped n = 14 and prepped n =
      14. Colonic segments were subjectively evaluated for residual stool that would
      potentially interfere with interpretation. Scores were given in the following
      categories: percentage of residual stool that was touching or nearly touching
      mucosa, the largest piece of retained stool, effectiveness of tagging, height of
      residual fluid, degree of distention, ease of interpretation, and reading time.
      RESULTS: Ease of the CT read (scale where 4 = optimal read) averaged 1.3 for the
      unprepped group and 2.3 for the prepped group. The mean read time averaged 17.5
      min for unprepped and 17.9 min for prepped. The degree of distention (scale where
      4 = well distended) averaged 3.7 for unprepped and 3.6 for prepped. Supine and
      prone images combined, the unprepped group had 160 segments with stool; prepped
      group had 58 segments. The amount of stool covering the mucosa in all segments
      averaged 1.6 (33%-66% coverage) in the unprepped group and 0.35 (<33% mucosal
      coverage) in the prepped group. The mean size of the largest piece of stool was
      33.67 mm for unprepped and 4.01 mm for prepped. Percentage of tagged stool was
      not significantly different between the groups (range of 94-98%). The height of
      residual fluid averaged 8.37 mm for unprepped and 13.4 mm for prepped. Three
      polyps in three patients were found during optical colonoscopy (OC) in the
      unprepped group (5, 6, and 10 mm), none of which were prospectively detected at
      CTC. Three polyps in three patients were detected during OC in the prepped group
      (5, 10, and 15 mm), two of which were prospectively detected at CTC. Two false
      positive lesions were observed at CTC in one patient in the prepped group.
      CONCLUSION: There was more stool in the unprepped group and while this factor did
      not slow down the reading time, it made the examination subjectively harder to
      interpret and likely caused the three polyps in this group to be missed. We
      conclude that a truly unprepped strategy that leaves significant residual stool,
      even if well tagged, is not desirable.

PMID- 16969602
TI  - Post-treatment fistulas in patients with rectal cancer: MRI with rectal
      superparamagnetic contrast agent.
AB  - MRI is the standard modality in the pre- and post-treatment evaluation of
      patients with rectal cancer, particularly in those cases with locally advanced
      disease. We routinely employ a superparamagnetic iron oxide (SPIO) contrast enema
      to distend the rectal lumen and achieve maximal tumor-to-lumen contrast gradient.
      This practice also allowed the identification of a fistula in 24% of patients
      treated for rectal cancer. Contrast agent-related low intensity signal could be
      seen filling the tract and eventually opacifying surrounding organs (i.e.,
      vagina) or collections (i.e., presacral abscess). Fistula formation after
      radiochemotherapy and surgery for rectal cancer is not uncommon. MRI with dark
      lumen contrast enema allows an effective demonstration of this complication in a
      high number of patients.

PMID- 16969603
TI  - The children's services interview: validity and reliability.
AB  - BACKGROUND: The Children Service Interview was designed as a brief measure of
      service use related to mental health problems in Great Britain. METHOD: We
      validated the Children's Services Interview against medical records from a sample
      of 87 children, and assessed test-retest reliability from 25 parents completing
      two interviews. We examined criterion validity by looking at the service use
      patterns of children attending clinics for different types of disorders. RESULTS:
      The Children's Services Interview showed high levels of face validity and
      moderate or better concordance with medical records as far as contacts were
      recorded in the case notes. Test-retest reliability was moderate or better apart
      from contacts with the voluntary sector, teachers, and the number and duration of
      appointments with some professionals. CONCLUSION: The study suggests the
      Children's Services Interview can extract moderately valid and reliable data on
      service use. DECLARATION OF INTEREST: Tamsin Ford was supported by a Wellcome
      Clinical Training Fellowship in Health Services Research while completing this
      work.

PMID- 16969604
TI  - Prevalence of psychoactive drug use among medical students in Rio de Janeiro.
AB  - BACKGROUND: Drug use and abuse may hamper learning capabilities and the
      development of technical skills in medical students and, therefore, the quality
      of care offered to patients. The aim of this investigation was to estimate the
      prevalence of psychoactive drug use among medical students of public universities
      in Rio de Janeiro, Brazil, and to identify characteristics associated with
      substance use. METHOD: This was a cross-sectional investigation designed to
      include all medical students of four universities. The final sample included
      1,054 students. Patterns of licit and illicit drug use (at least once in lifetime
      drug use, drug use in the last 30 days (LTD) and CAGE) before and during medical
      school were assessed by a multiple-choice, self-administered anonymous
      questionnaire. RESULTS: Alcohol abuse was more prevalent among male students from
      higher income families. Alcohol LTD use was more prevalent among male students
      with college-educated parents. Tobacco, cannabis and inhalant lifetime use was
      more prevalent among males and tranquillizer use among females. Tobacco, cannabis
      and tranquillizer lifetime use was more prevalent among students with divorced or
      dead parents. Inhalant lifetime use was more prevalent among students from higher
      income families. Students who had college-educated, divorced or dead parents or
      evidenced tobacco, cocaine or inhalant lifetime use were more prevalent among
      cannabis users. Male students from higher income families had higher prevalence
      of cocaine lifetime use. CONCLUSION: Substance use in this group of medical
      students is not widespread compared to rates reported for developed countries.
      Preventive efforts should focus on alcohol and cannabis use by medical students.

PMID- 16969606
TI  - Obliteration of the pelvic inlet by prophylene mesh and omentoplasty for
      enterocele.

PMID- 16969605
TI  - Gene expression profiles in the liver of mice irradiated with (60)Co gamma rays
      and treated with soybean isoflavone.
AB  - PURPOSE: To better understand the molecular mechanisms underlying the radio
      protective effect of soybean isoflavone that we observed in our recent animal
      experiments. MATERIALS AND METHODS: We utilized a cDNA microarray to investigate
      the expression profiles of 4,096 known genes in the livers of irradiated-mice
      with or without soybean isoflavone treatment. Dye swap approach was employed to
      control for gene-specific dye bias and quantitative real-time RT-PCR was
      performed on several genes to validate the cDNA microarray data. RESULTS:
      Compared with the control group, 68 genes were up-regulated and 28 genes were
      down-regulated in mice treated with irradiation alone, whereas only 6 genes were
      down-regulated and 35 genes were up-regulated in mice treated with soybean
      isoflavone. Interestingly, some of the down-regulated genes in the irradiated
      group, such as DNA repair and stress response genes and cytoskeleton-associated
      genes, which are markers of cellular damage after irradiation, were maintained at
      close to normal expression levels after soybean isoflavone treatment.
      CONCLUSIONS: Comparison of gene expression profiles in the livers of irradiated
      mice treated with or without soybean isoflavone suggested that soybean isoflavone
      may be an efficient tool to reverse irradiation damage of the liver through
      multiple-pathways and also provides important clues to further pursue the
      molecular mechanisms underlying the radio-protective activity of soybean
      isoflavone.

PMID- 16969607
TI  - Mucinous adenocarcinoma associated with chronic anal fistula reconstructed by
      gracilis myocutaneous flaps.
AB  - Mucinous adenocarcinoma associated with chronic anal fistula is extremely rare,
      and such tumors have often reached an advanced stage at the time of presentation.
      Here we report a case of mucinous adenocarcinoma associated with chronic anal
      fistula that involved repair with gracilis myocutaneous flaps and review other
      reported cases. A 67-year-old man with an approximate 30-year history of an anal
      fistula was referred to our hospital due to enlargement of the perianal
      induration accompanied by mucinous secretion and pain. Physical examination of
      the perianal region revealed an ulcerated and discharging lesion on the buttocks.
      Histologic examination of a biopsy specimen of the ulcerated lesion revealed
      mucinous adenocarcinoma. An abdominoperineal resection was performed with
      resection of the ischiorectal fossa, coccyx, part of the gluteus maximus, and the
      obturator internus. The extensive defect was repaired with bilateral gracilis
      myocutaneous flaps. The patient did not experience a decrease in the strength of
      hip adduction and survived for 58 months without recurrence until he died of
      pneumonia. The repair using myocutaneous flaps was considered to contribute to a
      physically active life without recurrence.

PMID- 16969608
TI  - Adult Hirschsprung's disease presenting as sigmoid volvulus: a case report and
      review of literature.
AB  - Sigmoid volvulus is a rare presentation of Hirschsprung's disease. A 38-year-old
      male presented with acute intestinal obstruction and a history of chronic
      constipation since childhood. Abdominal radiographs showed megarectum and
      megacolon with dissipated feces. Sigmoidoscopy revealed gangrenous bowel mucosa
      affecting the sigmoid colon. Emergency laparotomy revealed a grossly dilated
      bowel with concurrent gangrenous sigmoid volvulus. He was treated successfully
      with proctocolectomy with J-pouch-anal anastomosis and a defunctioning ileostomy.
      Histological analysis was consistent with short segment Hirschsprung's disease.
      Although uncommon, adult Hirschsprung's disease is a cause of chronic
      constipation and can present acutely with a sigmoid volvulus. Mortality in cases
      with sigmoid volvulus is greater than in cases without (15.4% vs. 0%). A better
      awareness of this condition will facilitate management.

PMID- 16969609
TI  - Cutting seton for pilonidal disease: a new approach.
AB  - I present a technique for dealing with chronic pilonidal disease that avoids use
      of general anesthesia, long hospital stay, complex wound care and prolonged
      disability that has so often been associated with more traditional surgical
      treatment in the past. Satisfactory resection was achieved by means of a single
      cutting seton (garrotte) in 8 patients, 5 males and 3 females ranging in age from
      18 years to 31 years, all of whom had had prior unsuccessful incision and
      drainage for long-standing disease with local abscesses and suppuration. The
      seton was applied in an ambulatory care setting under local anesthesia. It was
      tied and progressively tightened over a period of two weeks. Complete excision of
      the diseased area was achieved and revascularization of the wounds site occurred
      with optimum healing by secondary intention, leaving an acceptable scar. It
      required minimal wound care. There were no recurrences over an average follow-up
      period of 22.5 months. All patients were uniformly satisfied. The encouraging
      preliminary results for this novel technique suggest that it is simple, safe and
      effective. It requires evaluation in a larger series with longer follow-up.

PMID- 16969610
TI  - The place for colectomy and ileorectal anastomosis: a valid surgical option for
      ulcerative colitis?
AB  - BACKGROUND: Conflicting views regarding the use of ileorectal anastomosis (IRA)
      in ulcerative colitis (UC) exist and this controversy prompted us to review our
      experience, especially against the background of the current tendency to choose
      the ileal pouch-anal procedure (IPAA). METHODS: Thirty-two consecutive patients
      with IRA were studied. Complications, failure rate, reasons for failure and
      functional results were assessed. The median follow-up time was 3.5 years.
      RESULTS: The overall complication rate was 28%. The rectum was excised in 4
      patients, indicating a failure rate of 12%. The mean daily evacuation frequency
      was 5.6. Despite urgency occurring in one-third of the patients, continence
      function was well preserved. CONCLUSIONS: Employed on a selective basis, IRA is a
      safe procedure with low mortality and morbidity and good prospects for success in
      many patients with UC. The patients must be prepared to submit to life-long
      rectoscopy surveillance.

PMID- 16969611
TI  - Does a fibrin-collagen patch support early anastomotic healing in the colon? An
      experimental study.
AB  - BACKGROUND: The aim of this study was to evaluate the effect of absorbable fibrin
      collagen patch (FCP) during early colonic anastomotic healing in rats. METHODS:
      Prepubertal Wistar albino rats were randomly divided into 6 groups of 6 rats
      each. Colon was transected and then anastomosed with sutures (Group A),
      sutures+FCP (TachoComb; Nycomed, Austria) (Group AT) or only FCP (Group T). Rats
      were sacrificed either 3 or 7 days after the anastomosis. Anastomoses were
      evaluated for perianastomotic adhesion formation, bursting pressures and
      histological features. RESULTS: Perianastomotic adhesion formation was
      significant in Groups AT and T. Bursting pressures were in higher group AT than
      in Group A on postoperative day 3 and lower on day 7 (p < 0.05). Histological
      examinations revealed an increase in inflammatory cells in Group T on day 3 and
      decreased wound healing in Group AT when compared to Group A on day 7 (p < 0.05).
      CONCLUSIONS: In the early period of anastomotic healing, FCP supports anastomotic
      integrity. However, it also causes an inflammatory reaction which may increase
      the time necessary for healing process. Thus, the use of this biomaterial should
      be preferred in only selective clinical cases with a careful follow-up.

PMID- 16969612
TI  - A new combined form significantly improves accuracy of pathological diagnosis in
      inflammatory bowel disease in absence of the clinicopathological conference.
AB  - BACKGROUND: Proper management of patients with inflammatory bowel disease depends
      upon a definitive diagnosis, which is best arrived at in the clinicopathological
      conference (CPC). The aim of the study was to assess the impact of a combined
      clinical and pathological form called Performa on the definitive diagnostic rate
      and to see if this improvement was comparable with results achieved with CPCs.
      METHODS: Between June 2003 and December 2003, 77 consecutive patients were
      included in the study. Histological data recorded on the performa were reviewed
      by one consultant pathologist after the initial reporting to see if there was any
      change in diagnosis. All cases were also discussed in the CPC as per guidelines.
      RESULTS: The use of the combined form significantly increased the definitive
      diagnostic rate by decreasing the unclassifiable group by 23.6%, and was
      comparable to that achieved by CPC. CONCLUSIONS: In the absence of a CPC, the
      proposed form is an efficient substitute.

PMID- 16969613
TI  - Evaluation of anastomotic microcirculation after low anterior rectal resection:
      an experimental study with different reconstruction forms in dogs.
AB  - BACKGROUND: Data on anastomotic microcirculation of coloanal anastomoses are
      contradictory. Therefore, it was the aim of the present study to investigate
      perianastomotic blood perfusion in a standardized experimental setting comparing
      three forms of reconstruction using laser fluorescence videography, a new method
      for the evaluation of microcirculation. METHODS: After a standardised rectal
      resection in dogs, reconstruction was performed as straight end-to-end (n = 6),
      side-to-end (n = 6), or J-pouch (n = 6) coloanal anastomosis. Bowel perfusion was
      evaluated using IC-View laser fluorescence videography. RESULTS: The perfusion
      index was significantly reduced in all three groups compared to the reference
      regions: endto-end anastomosis, median, 93% (range, 63%-136%); side-to-end
      anastomosis, 65% (35%-138%); colonic-J-pouch anal anastomosis, 52% (32%-72%); p <
      0.001). CONCLUSIONS: Straight coloanal anastomoses provide better anastomotic
      microcirculation after rectal resections than colonic-J-pouch anal anastomoses or
      side-to-end anastomoses. However this effect does not seem to be decisive for the
      prevention of anastomotic leaks.

PMID- 16969614
TI  - Fistula in ano: anatomoclinical aspects, surgical therapy and results in 844
      patients.
AB  - BACKGROUND: Several new therapies, including advancement flaps and fibrin glue,
      have been proposed for fistula in ano, with conflicting results. Most colorectal
      surgeons continue to use classic methods, e.g. fistulotomy, fistulectomy, a
      combined method, loose or cutting seton, and rubber loop. The aim of the present
      study is to report the outcome of our patients, operated on by such methods.
      METHODS: We retrospectively reviewed the clinical records of 844 patients treated
      for anal fistula over a 30-year period, and assessed fistula morphology, surgical
      procedure and healing period. For patients treated 2 or more years prior to this
      study, we evaluated rates of persistent fistula and relapse, as well as
      prevalence of incontinence and patient satisfaction. RESULTS: The majority of
      patients had trans-sphincteric fistulae (58.3%). We observed 274 secondary
      extensions (32.5%); these were common in all fistula types except for
      intrasphincteric fistulae. Most patients were treated by fistulotomy alone (594
      patients, 70.4%) or by the combined fistulectomy-fistulotomy method (237
      patients, 28.1%), with or without loose seton. All patients with trans-, supra-
      and extrasphincteric fistulae were re-examined in the operations theatre. Follow
      up data were available for 652 (87%) of 751 patients at least two years after
      surgery. The anal fistula persisted in 3.2% and recurred in 2.1% of cases. A
      second procedure lowered the initial rate of unsuccessful operations from 5.3% to
      2.5%. Continence disorders were reported in 6.9% of patients: 4.0% complained of
      incontinence to gas, 2.6% to liquid and 0.3% to solid feces. CONCLUSIONS:
      Fistulotomy and fistulectomy with loose seton supported by preoperative anal
      manometry and postoperative evaluation under anaesthesia are followed by good
      clinical and functional results.

PMID- 16969615
TI  - Early effects of fibrin sealant on colonic anastomosis in rats: an experimental
      and case-control study.
AB  - BACKGROUND: Leakage from colonic anastomoses leads to mortality and morbidity.
      Fibrin adhesives can be used to increase the strength of the anastomosis. In this
      study, we evaluated the early effects of fibrin sealant and hyaluronic acid
      carboxymethylcellulose on colonic anastomosis in rats. METHODS: Anastomoses were
      made in the descending colon of 38 female Wistar-Albino rats, in three groups:
      control group (n = 12), group 1 treated with hyaluronic acid
      carboxymethylcellulose (n = 16), and group 2 treated with fibrin sealant (n =
      10). After 72 hours, adhesion scores, bursting pressure, rupture strength and
      histopathologic healing scores were evaluated. RESULTS: Due to postoperative
      mortality, we evaluated 10, 10 and 9 rats in the control group and in groups 1
      and 2, respectively. Of these, we excluded 4, 5 and 4 rats that had
      macroperforations at autopsy. In the remaining rats, bursting pressure (123.2 +/-
      14.8 mmHg) and rupture strength (400 +/- 16 mg) in the fibrin sealant group were
      significantly greater than in the two other groups ( CONTROL: 68.0 +/- 10.6 p =
      0.006 and 325 +/- 52 p = 0.009; Group 1: 74.0 +/- 9.8 p = 0.03, 330 +/- 27 p =
      0.016). However, we did not observe any significant difference between adhesion
      scores (2.5 +/- 0.6, 2.0 +/- 0.7, 2.0 +/- 0.7, p = 0.343). CONCLUSIONS: In this
      experimental study, fibrin sealant increased bursting pressure and rupture
      strength of colonic anastomoses while hyaluronic acid-carboxymethylcellulose had
      no effects in rats, but both of them showed no effect on adhesion scores. In
      order to use fibrin sealant to decrease the rate of early leakages from colonic
      anastomoses, further studies have to be performed.

PMID- 16969616
TI  - Strategies of follow-up for colorectal cancer: a survey of the American Society
      of Colon and Rectal Surgeons.
AB  - BACKGROUND: The postoperative surveillance of patients who have undergone
      curative treatment for colorectal cancer (CRC) is controversial. The aim of this
      study was to investigate the follow-up practice of colorectal surgeons in the
      United States. METHODS: A postal survey was sent to 1641 active members of the
      American Society of Colon and Rectal Surgeons practicing in the United States to
      assess the frequency of follow-up and the methods used in the surveillance of
      asymptomatic patients following curative surgery for CRC. RESULTS: Only 582 (36%)
      of the questionnaires that were sent were returned fully completed. Of these, 173
      surgeons (30%) followed their patients according to guidelines. Ninety-four
      percent of surgeons during the first year and 81% during the second year saw
      their patients regularly every 3 or 6 months. The most widely used tests were
      colonoscopy and carcinoembryonic antigen (CEA) testing. There was wide
      discrepancy in the frequency of follow-up and techniques employed, with only
      about 50% of surgeons following recommended practice. CONCLUSIONS: Surveillance
      strategies mainly rely on clinical examination, CEA monitoring and colonoscopy.
      No clear consensus on surveillance programs for CRC patients exists.

PMID- 16969617
TI  - Prospective randomized trial comparing stapled hemorrhoidopexy versus closed
      Ferguson hemorrhoidectomy.
AB  - BACKGROUND: Ferguson hemorrhoidectomy is believed to result in less postoperative
      pain because of a closed wound. Stapled hemorrhoidopexy, without a perianal
      wound, should thus have lesser pain. We conducted a prospective randomized trial
      to compare stapled hemorrhoidopexy (SH) with Ferguson hemorrhoidectomy (FH).
      METHODS: Fifty patients with third-degree or early fourthdegree hemorrhoids who
      required surgery were recruited. Patients were prospectively randomized to
      receive either FH or SH. Data collected include operative time, hospital stay,
      fecal incontinence and pain scores, morbidity and complications. RESULTS: SH
      patients had less pain in the early postoperative period. There were no
      significant differences in hospital stay or major complications. One patient
      after SH required emergency reintervention for thrombosed hemorrhoids distal to
      the staple line. FH patients had more minor problems of bleeding, wound discharge
      and pruritus. Fecal incontinence was similar in the 2 groups but two of the three
      patients with daily incontinence to gas after SH claimed that their lifestyle was
      affected. CONCLUSIONS: SH is safe to perform and results in less postoperative
      pain as well as less minor morbidity. Early reintervention and incontinence to
      gas compromising lifestyle occurred only after SH.

PMID- 16969618
TI  - Does sodium hyaluronate- and carboxymethylcellulose-based bioresorbable membrane
      (Seprafilm) decrease operative time for loop ileostomy closure?
AB  - BACKGROUND: Adhesions can result in serious clinical complications and make
      ileostomy closure, which is relatively simple procedure into a complicated and
      prolonged one. The use of sodium hyaluronate and carboxymethyl cellulose membrane
      (Seprafilm) was proven to significantly reduce the postoperative adhesions at the
      site of application. The aim of this study was to assess the incidence and
      severity of adhesions around a loop ileostomy and to analyze the length of time
      and morbidity for mobilization at the time of ileostomy closure with and without
      the use of Seprafilm. METHODS: Twenty-nine surgeons from 15 institutions
      participated in this multicenter prospective randomized study. 191 patients with
      loop ileostomy construction were randomly assigned to either receive Seprafilm
      under the midline incision and around the stoma (Group I), only under the midline
      incision (Group II), or not to receive Seprafilm (Group III). At ileostomy
      closure, adhesions were quantified and graded; operative morbidity was also
      measured. RESULTS: All 3 groups were comparable relative to gender, mean age and
      number of patients with prior operations (26, 25 and 19, respectively). Group II
      patients were significantly more likely to have pre-existing adhesions than Group
      III patients (30.6% vs. 14.1%, p = 0.025). At stoma mobilization, significantly
      more patients in Group III than in Group I had adhesions around the stoma (95.2%
      vs. 82.3%, p = 0.021). Mean operative times were 27, 25, and 28 minutes,
      respectively (p = 0.38), with significant differences among sites. There was no
      significant difference in the number of patients needing myotomy or enterotomy
      (29, 27 and 24 patients, respectively), nor in the number of postoperative
      complications (7, 9 and 7 patients, respectively). CONCLUSIONS: When consistently
      applied, Seprafilm significantly decreased adhesion formation around the stoma
      but not operative times without any increase in the need for myotomy or
      enterotomy. These findings were not seen in the overall study population possibly
      due to the large number of surgeons using a variety of application techniques.

PMID- 16969619
TI  - The treatment of hemorrhoids: guidelines of the Italian Society of Colorectal
      Surgery.

PMID- 16969620
TI  - An evidence-based treatment algorithm for anal fissure.
AB  - Guidelines for the treatment of anal fissure have been published in the USA and
      UK but differ. Many centers follow guidelines based on local experience. In
      December 2005, we met with the aim of developing an evidence-based treatment
      algorithm for anal fissure, applicable to both primary and secondary care. This
      algorithm may rationalize the treatment of anal fissure in primary and secondary
      care settings.

PMID- 16969621
TI  - Preoperative assessment of the circumferential margin in rectal cancer is more
      informative in treatment planning than the T stage.
AB  - Preventing local recurrence in rectal cancer means achieving a free
      circumferential resection margin (CRM) through an optimal combination of surgery,
      radiotherapy and chemotherapy. This requires a differentiation between primary
      resectable and locally advanced cancers. The T staging used, while being a
      powerful marker of prognosis, has two major downsides. First, accuracy of
      preoperative predictions of the T stage is unacceptably low. Second, a T3 tumor
      can be either primary resectable or locally advanced. A review of the literature
      was performed to establish the value of the CRM as the preferred preoperative
      staging classification, and to establish the feasibility of predicting the CRM
      using modern day, high-resolution imaging techniques. We advocate using the CRM
      as preoperative staging classification. Magnetic resonance imaging and multislice
      computed tomography offer an accurate pre-operative prediction of the CRM, and
      staging by means of predicted CRM offers the ideal combination of accuracy and
      clinical relevance.

PMID- 16969622
TI  - Experimental evaluation of the elastic determinants of myocardial function in
      vivo.
AB  - Shortening of myocardial fibers occurs following force development in those
      fibers. The extent, speed and timing of shortening are determined by kinetics and
      extent of force. However, shortening is also influenced by the
      elastance/viscosity of the muscle tissue, because that determines the coupling
      between force and shortening. In the in vivo dog heart, we estimated that
      coupling by measuring local myocardial force and fiber shortening independently
      under various conditions. We determined the effect of positive and negative
      inotropy (by intracoronary injection of dobutamine and acetylcholine,
      respectively), and of dysfunctional contraction produced by local
      ischemia/reperfusion and BDM. Under baseline and both positive and negative
      intropy, most shortening occurred during systole, and dobutamine increased the
      proportion of total shortening in early systole from 45.8 +/- 8.5% to 74.9 +/-
      9.6%. During reperfusion following ischemia, shortening in early systole was
      markedly reduced to 16.5 +/- 2.9; BDM caused a similar reduction to 16.5 +/- 8.1.
      Most of the shortening occurred during early diastole (53.0 +/- 6.8 for
      reperfusion, and 54.0 +/- 10.3 for BDM). These effects were all reversible. It is
      concluded that energetic efficiency is greatly affected by the elastic properties
      coupling force and shortening. Thus appropriate analysis of muscle function must
      take into account the changeable elastic properties of the tissue-both force and
      shortening, and their interaction must be considered.

PMID- 16969623
TI  - Basilar impression in osteogenesis imperfecta: can it be treated with halo
      traction and posterior fusion?
AB  - Basilar impression (BI) and hydrocephalus complicating osteogenesis imperfecta
      (OI) is usually treated by anterior transoral decompression and posterior
      fixation. Nevertheless, it may be questioned if posterior fusion following axial
      halo traction is adequate in patients with symptomatic BI complicating OI. We
      report on a case with progressive symptomatic hydrocephalus and BI complicating
      OI that was successfully treated by halo traction followed by posterior
      occipitocervical fusion. However, after a symptom free interval of 2 years the
      patient suffered from recurrence of symptomatic hydrocephalus needing additional
      ventriculoperitoneal (VP) shunt placement. In conclusion, posterior fusion
      without additional VP shunt placement may not be effective in the long term for
      ameliorating symptoms and signs and halting progressive hydrocephalus in BI
      complicating OI.

PMID- 16969624
TI  - Low-dose aspirin before intracranial surgery--results of a survey among
      neurosurgeons in Germany.
AB  - BACKGROUND: Increasing numbers of patients presenting for intracranial surgery
      are receiving concurrent medication with low-dose aspirin, leading to
      dysfunctional circulating platelets, which might increase the peri-operative risk
      of bleeding. OBJECTIVE: To survey the opinions and working practices of
      neurosurgical facilities in Germany regarding patients who present with low-dose
      aspirin medication before elective intracranial surgery. Methods. Questionnaires
      were sent to 210 neurosurgical facilities asking five main questions: (1) the
      adherence of any policy of stopping aspirin pre-operatively, (2) the personal
      risk assessment for patients with brain surgery under low-dose aspirin
      medication, (3) the preferred method of treatment for excessive bleeding in this
      context, (4) personal knowledge of haemorrhagic complications in this group of
      patients, and (5) the characteristics of the neurosurgical units concerned.
      RESULTS: There were 138 (65.7%) valid responses. Of the respondents, 111 (80.4%)
      had a departmental policy for the discontinuation of pre-operative aspirin
      treatment. The mean time for discontinuation of aspirin pre-operatively was 7.3
      days (range: 0-21 days). 107 respondents (77.5%) considered that patients taking
      low-dose aspirin were at increased risk for excessive peri-operative haemorrhage,
      and 80 (58%) reported having personal experience of such problems. Ninety-seven
      respondents (70.3%) would use special medical therapy, preferably desmopressin,
      if haemorrhagic complications developed intra-operatively. The mean amount of
      intracranial operations per year in each neurosurgical facility was 494 (range:
      50-1700). CONCLUSIONS: The majority of neurosurgical facilities in Germany have
      distinct departmental policies concerning the discontinuation of low-dose aspirin
      pre-operatively, with an average of 7.3 days. Three-quarter of the respondents
      felt that aspirin was a risk factor for haemorrhagic complications associated
      with intracranial procedures, and more than half of the interviewees reported
      having personal experience of such problems. Various medicamentous methods of
      counteracting aspirin-induced platelet dysfunction and excessive bleeding in this
      context are discussed and evaluated.

PMID- 16969625
TI  - Differentiated effect of ageing on the enzymes of Krebs' cycle, electron transfer
      complexes and glutamate metabolism of non-synaptic and intra-synaptic
      mitochondria from cerebral cortex.
AB  - The effect of ageing on the activity of enzymes linked to Krebs' cycle, electron
      transfer chain and glutamate metabolism was studied in three different types of
      mitochondria of cerebral cortex of 1-year old and 2-year old male Wistar rats. We
      assessed the maximum rate (V(max)) of the mitochondrial enzyme activities in non
      synaptic perikaryal mitochondria, and in two populations of intra-synaptic
      mitochondria. The results indicated that: (i) in normal, steady-state cerebral
      cortex the values of the catalytic activities of the enzymes markedly differed in
      the various populations of mitochondria; (ii) in intra-synaptic mitochondria,
      ageing affected the catalytic properties of the enzymes linked to Krebs' cycle,
      electron transfer chain and glutamate metabolism; (iii) these changes were more
      evident in intra-synaptic "heavy" than "light" mitochondria. These results
      indicate a different age-related vulnerability of subpopulations of mitochondria
      in vivo located into synapses than non-synaptic ones.

PMID- 16969626
TI  - EEG evidence of gender differences in a motor related CNV study.
AB  - In the present study gender differences related to the contingent negative
      variation (CNV) were investigated. A series of two acoustic stimuli was presented
      to participants across a wide age range. The first stimulus was consistent
      throughout the experiment whereas the second one was either a high frequency or a
      low frequency tone. One of them had to be answered by a button press (go
      condition) the other did not require any response (nogo condition). Between the
      first and the second tone there was a time period of two seconds in which the CNV
      appeared as a slow negative potential shift. Within this episode data were
      analysed with respect to gender differences. Statistical analysis revealed
      topographical differences between men and women in go conditions for both left
      and right index finger movements. Differences were found over frontal regions
      where women showed higher brain activity than men and over temporo-parietal
      regions where men produced higher brain activity than women. In order to explain
      the fact that only in "go" conditions significant gender differences occurred we
      introduce the phenomenon of implicit learning. Due to implicit learning assumed
      predictions related to S2 might have occurred from time to time. This is so,
      because a 50% chance for one of two different stimuli to occur leads to
      reasonable assumed predictions after two or more stimuli of a kind occurring in a
      series. The present data now provide evidence that if such assumed prediction or
      expectancy is directed towards an upcoming demand to act then brain activity is
      subject to gender differences. Further studies providing controlled sequences of
      "go" conditions versus "nogo" conditions have to be done to prove this idea true.

PMID- 16969627
TI  - Abeta peptides as one of the crucial volume transmission signals in the trophic
      units and their interactions with homocysteine. Physiological implications and
      relevance for Alzheimer's disease.
AB  - Amyloid peptides (Abeta) can operate as volume transmission (VT) signals since
      they are continuously released from cells of the central nervous system and
      diffuse in the extra-cellular space of the brain. They have both regulatory and
      trophic functions on cellular networks. In agreement with Abeta regulatory
      actions on glial-neuronal networks, the present paper reports new findings
      demonstrating that intrastriatal injections of Abeta peptides reduce striatal
      tyrosine hydroxylase, increase striatal GFAP immunoreactivities and lower pain
      threshold in experimental rats. Furthermore, it has been demonstrated that
      exogenous homocysteine (Hcy) binds Abeta(1-40) favouring its beta-sheet
      conformation both in vitro and in vivo and hence the formation of beta-fibrils
      and development of neurotoxicity. Thus, the hypothesis is discussed that Abeta
      peptides represent crucial VT-signals in the brain and their action is altered by
      dysmetabolic signals such as high Hcy extra-cellular levels, known to be an
      important risk factor for Alzheimer's disease.

PMID- 16969628
TI  - Role of glucagon in the control of heat production in ducklings.
AB  - Glucagon is known to be a central modulator of neural activity and a peripheral
      thermogenic effect. The purpose of this study was to better understand the role
      of glucagon in the control of heat production, shivering and particularly as a
      mediator of nonshivering thermogenesis (NST) in ducklings. In order to study the
      mechanism of NST, an intracerebroventricular (i.c.v.) injection of glucagon (10(
      7) M) in to thermoneutral (TN), chronically glucagon treated (GT) and cold
      acclimatized (CA) ducklings exposed to acute cold (4 degrees C) or a
      thermoneutrality (25 degrees C), was performed. At 25 degrees C ambient
      temperature (Ta), the metabolic rate (MR) remained unchanged after glucagon
      injection. At 4 degrees C Ta i.c.v. glucagon injection, no significant change in
      MR was observed in GT and CA ducklings during 160 min of cold exposure, whereas
      there was 63% decrease in MR in (TN) ducklings (5.02 +/- 0.1 2 vs 7.91 +/- 0.1 4
      W/kg(-1) p < 0.05). Shivering activity was completely suppressed in TN and GT
      ducklings after glucagon administration. The NST was estimated to be 3.26 W/kg.
      This findings suggest that glucagon administered into the brain has no
      thermogenic effect but could be involved in the central control of somatic
      motricity, and here we demonstrated for the first time, of our knowledge, that
      central glucagon have a role in the development of nonshivering thermogenesis
      during prolonged cold via an inhibition of shivering in birds.

PMID- 16969629
TI  - Molecular evidence that zucchini yellow fleck virus is a distinct and variable
      potyvirus related to papaya ringspot virus and Moroccan watermelon mosaic virus.
AB  - Zucchini yellow fleck virus (ZYFV, genus Potyvirus) infects cultivated or wild
      cucurbits in the Mediterranean basin and occasionally causes severe damage in
      crops. Biological and serological data tend to indicate that ZYFV is related to
      other cucurbit-infecting potyviruses, mainly papaya ringspot virus (PRSV) and
      Moroccan watermelon mosaic virus (MWMV). In order to establish unambiguously the
      taxonomic status of ZYFV, the sequence of the 3' part of the genome -
      encompassing the CP coding region - of two ZYFV strains originating from Italy
      and France was obtained and compared with other potyviruses. The results obtained
      indicate that ZYFV belongs to a distinct potyvirus species, related to but
      different from PRSV and MWMV.

PMID- 16969631
TI  - Pushing up daisies: implicit and explicit language in oncologist-patient
      communication about death.
AB  - GOALS OF WORK: Although there are guidelines regarding how conversations with
      patients about prognosis in life-limiting illness should occur, there are little
      data about what doctors actually say. This study was designed to qualitatively
      analyze the language that oncologists and cancer patients use when talking about
      death. SUBJECTS AND METHODS: We recruited 29 adults who had incurable forms of
      cancer, were scheduled for a first-time visit with one of six oncologists
      affiliated with a teaching hospital in Australia, and consented to having their
      visit audiotaped and transcribed. Using content analytic techniques, we coded
      various features of language usage. MAIN RESULTS: Of the 29 visits, 23 (79.3%)
      included prognostic utterances about treatment-related and disease-related
      outcomes. In 12 (52.2%) of these 23 visits, explicit language about death
      ("terminal," variations of "death") was used. It was most commonly used by the
      oncologist after the physical examination, but it was sometimes used by patients
      or their kin, usually before the examination and involving emotional questioning
      about the patient's future. In all 23 (100%) visits, implicit language
      (euphemistic or indirect talk) was used in discussing death and focused on an
      anticipated life span (mentioned in 87.0% of visits), estimated time frame
      (69.6%), or projected survival (47.8%). CONCLUSIONS: Instead of using the word
      "death," most participants used some alternative phrase, including implicit
      language. Although oncologists are more likely than patients and their kin to use
      explicit language in discussing death, the oncologists tend to couple it with
      implicit language, possibly to mitigate the message effects.

PMID- 16969632
TI  - Primary mantle cell lymphoma of the conjunctiva: a case report.
AB  - Primary non-Hodgkin's lymphomas of the conjunctiva are uncommon. They are almost
      exclusively extranodal marginal zone B-cell lymphomas/mucosa-associated lymphoid
      tissue lymphomas. In this study, we report an extremely rare case of conjunctival
      mantle cell lymphoma in a 78-year-old man, presenting as a unilateral epibulbar
      mass.

PMID- 16969633
TI  - Primary hypertrophic osteoarthropathy (pachydermoperiostosis): a case report.
AB  - Hypertrophic osteoarthropathy is characterized by digital clubbing and periosteal
      reaction of long bones. Most cases are associated with malignancy or other
      conditions such as congenital heart disease, liver cirrhosis, pulmonary fibrosis,
      biliary atresia, and gastrointestinal polyps. We report a 19-year-old man
      presenting with arthritis, broadening of the fingers and clubbing of the fingers
      and toes for the previous 3 years. The ankles and knees were swollen. X-rays
      showed periosteal apposition. The search for a secondary cause remained negative.
      In cases of arthralgia/arthritis together with clubbed fingers, consideration
      must be given to hypertrophic osteoarthropathy. The primary or idiopathic form is
      rare and has a good prognosis.

PMID- 16969634
TI  - Decreased protein S activity is related to the disease activity of Behcet's
      disease.
AB  - We wanted to see whether the active inflammation in Behcet's disease (BD) can
      cause a thrombotic disorder by decreasing the protein S (PS) activity, and we
      evaluated the relationship between the decreased PS activity and the disease
      activity of BD. We included 122 patients with BD whose PS activity levels were
      measured. In 51 patients, the PS activity was measured again when there were
      changes in the number of items of "The Behcet's Disease Current Activity Form
      (BDCAF)". The thrombosis rate was 2.5% (3/122), and the PS activity was low in
      all three of the patients with thrombosis. The incidence of low PS activity in
      the total 122 BD patients was 27% (33/122). The incidence of the low PS activity
      in the active BD patients was 33.7% (31/92), and this was significantly more
      frequent than in the inactive BD patients, (6.7%, 2/30) (chi(2)-test, P value =
      0.0038). The decrease of PS activity had good correlation with the increase of
      the number of BDCAF items (r = -0.351, P value = 0.012). The PS activity decrease
      is related to the BD activity. The low PS activity can be the risk factor for
      thrombotic disorder and also the activity marker for BD and other inflammatory
      diseases.

PMID- 16969635
TI  - The occurrence of sensorineural hearing loss in a patient with myeloperoxidase
      anti-neutrophil cytoplasmic antibody-related microscopic polyangiitis.

PMID- 16969636
TI  - Common marmosets (Callithrix jacchus) do not utilize social information in three
      simultaneous social foraging tasks.
AB  - Social foraging is suggested to increase foraging efficiency, as individuals
      might benefit from public information acquired by monitoring the foraging
      activities of other group members. We conducted a series experiments with captive
      common marmosets (Callithrix jacchus) to investigate to what extent marmosets
      utilize social information about food location when foraging simultaneously with
      conspecifics. Subjects were confronted with dominant and subordinate
      demonstrators in three experiments which differed in the amount of information
      about food location available to the demonstrators. In all three experiments, the
      focal subjects' performance in the social condition was not enhanced in
      comparison to a non-social control condition. Because we could rule out
      kleptoparasitism and aggressive displacements as explanations, we argue that the
      subjects' tendency for scramble competition by avoiding others and dispersing
      over the foraging area seems to inhibit or mask the acquisition of social
      information about the location of rewarded patches.

PMID- 16969637
TI  - Usefulness of high-b-value diffusion-weighted imaging in acute cerebral
      infarction.
AB  - The aim of our study was to investigate the usefulness of high-b-value diffusion
      weighted (DW) MR imaging in patients with acute cerebral infarction. DW images at
      b-values of 1,000, 2,000, and 3,000 s/mm(2) were performed for 32 patients 48 h
      after the onset of stroke using a 1.5 T clinical imager. The area of restricted
      diffusion became more distinct and extensive with increasing b-value in 19 of 32
      patients, especially in patients with the atherothrombotic-type cerebral
      infarction. The visualized extent of infarction was almost the same among the
      area of restricted diffusion on the b=3,000 ADC map, b=3,000 DWI and final
      infarction in 12 of 15 patients. High-b-value DWI provided better identification
      of lesion extension in the cerebral ischemia. It is suggested that the size of
      the final infarction or irreversible cytotoxic edema is more predictable on high
      b-value DWIs than on the usual b=1,000 DWI.

PMID- 16969638
TI  - Rotator cuff tears: assessment with MR arthrography in 275 patients with
      arthroscopic correlation.
AB  - We assessed the diagnostic performance of magnetic resonance (MR) arthrography in
      the diagnosis of articular-sided partial-thickness and full-thickness rotator
      cuff tears in a large symptomatic population. MR arthrograms obtained in 275
      patients including a study group of 139 patients with rotator cuff tears proved
      by arthroscopy and a control group of 136 patients with arthroscopically intact
      rotator cuff tendons were reviewed in random order. MR imaging was performed on a
      1.0 T system (Magnetom Expert, Siemens). MR arthrograms were analyzed by two
      radiologists in consensus for articular-sided partial-thickness and full
      thickness tears of the supraspinatus, infraspinatus, and subscapularis tendons.
      At arthroscopy, 197 rotator cuff tears were diagnosed, including 105 partial
      thickness (93 supraspinatus, nine infraspinatus, three subscapularis) and 92 full
      thickness (43 supraspinatus, 20 infraspinatus, 29 subscapularis) tendon tears.
      For full-thickness tears, sensitivity, specificity, and accuracy were 96%, 99%,
      and 98%, respectively, and for partial tears 80%, 97%, and 95%, respectively.
      False negative and positive assessments in the diagnosis of articular-sided
      partial-thickness tears were predominantly [78% (35/45)] observed with small
      articular-sided (Ellman grade1) tendon tears. MR arthrography is highly accurate
      in the diagnosis of full-thickness rotator cuff tears and is accurate in the
      diagnosis of articular-sided partial-thickness tears. Limitations in the
      diagnosis of partial-thickness tears are mainly restricted to small articular
      sided tears (Ellman grade 1) due to difficulties in differentiation between fiber
      tearing, tendinitis, synovitic changes, and superficial fraying at tendon
      margins.

PMID- 16969639
TI  - The effects of varying time under tension and volume load on acute neuromuscular
      responses.
AB  - The purpose of this study was to examine the effects of different methods of
      measuring training volume, controlled in different ways, on selected variables
      that reflect acute neuromuscular responses. Eighteen resistance-trained males
      performed three fatiguing protocols of dynamic constant external resistance
      exercise, involving elbow flexors, that manipulated either time-under-tension
      (TUT) or volume load (VL), defined as the product of training load and
      repetitions. Protocol A provided a standard for TUT and VL. Protocol B involved
      the same VL as Protocol A but only 40% concentric TUT; Protocol C was equated to
      Protocol A for TUT but only involved 50% VL. Fatigue was assessed by changes in
      maximum voluntary isometric contraction (MVIC), interpolated doublet (ID), muscle
      twitch characteristics (peak twitch, time to peak twitch, 0.5 relaxation time,
      and mean rates of force development and twitch relaxation). All protocols
      produced significant changes (P <or= 0.05) in the measures considered to reflect
      neuromuscular fatigue, with the exception of ID. Fatigue was related to an
      increase in either TUT or VL with greater fatigue, as reflected by MVIC and
      peripheral measures, being associated with differences in TUT. The lack of change
      in ID suggests that fatigue was more related to peripheral than central
      mechanisms. It was concluded that the load and contraction velocities of the
      repetitions have different effects on acute neuromuscular responses and should,
      therefore, be clearly calculated when describing training volume for dynamic
      constant external resistance exercise training.

PMID- 16969640
TI  - Relationship between ace genotype and short duration aerobic performance
      development.
AB  - We have previously demonstrated that, ACE D allele may be related with a better
      performance in short duration aerobic endurance in a homogeneous cohort with
      similar training backgrounds. We aimed to study the variation in the short
      duration aerobic performance development amongst ACE genotypes in response to
      identical training programs in homogeneous populations. The study group consisted
      of 186 male Caucasian non-elite Turkish army recruits. All subjects had undergone
      an identical training program with double training session per day and 6 days a
      week for 6 months. Performances for middle distance runs (2,400 m) were evaluated
      on an athletics track before and after the training period. ACE gene
      polymorphisms were studied by PCR analysis. The distribution of genotypes in the
      whole group was 16.7% II, n=31; 46.2% ID, n=86; 37.1% DD, n=69. Subjects with ACE
      DD genotype had significantly higher enhancement than the ID (P<0.01) and II
      (P<0.05) genotype groups. Around 2,400 m performance enhancement ratios showed a
      linear trend as ACE DD>ACE ID>ACE II (P value for Pearson chi2=0.461 and P value
      for linear by linear association=0.001). ACE DD genotype seems to have an
      advantage in development in short-duration aerobic performance. This data in
      unison with the data that we have obtained from homogenous cohorts previously is
      considered as an existence of threshold for initiation of ACE I allele
      effectiveness in endurance performance. This threshold may be anywhere between 10
      and 30 min with lasting maximal exercises.

PMID- 16969641
TI  - No changes in lung function after a saturation dive to 2.5 MPa with intermittent
      reduction in Po2 during decompression.
AB  - Decompression stress and exposure to hyperoxia may cause a reduction in transfer
      factor of the lung for carbon monoxide and in maximal aerobic capacity after deep
      saturation dives. In this study lung function and exercise capacity were assessed
      before and after a helium-oxygen saturation dive to a pressure of 2.5 MPa where
      the decompression rate was reduced compared with previous deep dives, and the
      hyperoxic exposure was reduced by administering oxygen intermittently at
      pressures of 50 and 30 kPa during decompression. Eight experienced divers of
      median age 41 years (range 29-48) participated in the dive. The incidence of
      venous gas microemboli was low compared with previous deep dives. Except for one
      subject having treatment for decompression sickness, no changes in lung function
      or angiotensin converting enzyme, a marker of pulmonary endothelial cell damage,
      were demonstrated. The modified diving procedures with respect to decompression
      rate and hyperoxic exposure may have contributed to the lack of changes in lung
      function in this dive compared with previous deep saturation dives.

PMID- 16969642
TI  - [Somatoform pain disturbance as the result of trauma].
AB  - Orthopedic specialists and emergency surgeons are often confronted with
      somatoform disorders, which can be the result of traumatization, and they
      frequently do not recognize this. A combination of pain and several other
      physical symptoms is typical for somatization, and in these circumstances a
      psychosocial history should be elicited as a precaution before an elective
      operation is considered. Recognition of somatization with subsequent referral to
      more appropriate professional care (e.g., center for multimodal pain therapy,
      psychosomatic clinic) is crucial. We describe an interesting and instructive
      case, which it is hoped will help practitioners to recognize such patients and
      deal with their cases in the correct manner.

PMID- 16969643
TI  - [Minimally invasive unicondylar knee replacement with computer navigation].
AB  - METHODS: From January 2003 to July 2005 a total of 50 St Georg medial knee
      monosleds with metal-backed tibial components in stably seated form and Uniglide
      prostheses (Alphanorm/Corin) with mobile bearing onlays were implanted in
      minimally invasive operations. Postoperatively the alignment-especially of the
      tibial components-was investigated, to check whether we had achieved the dorsal
      slope we had been aiming at, i.e. 5-7 degrees , in the region of these knee
      replacements. RESULTS: Before surgery there were initial malalignments of up to
      10 degrees varus and 3 degrees valgus. All leg axes were restored to between -3
      degrees and +3 degrees . The desired dorsal slope of 5-7 degrees for the knee
      monosleds relative to the tibial component was realized, the average slope being
      5.3 degrees . The a-p alignment of the tibial component and of the femoral
      component was correct. CONCLUSIONS: Use of the navigation system leads to more
      accurate and reproducible results in terms of tibial dorsal slope, which is
      extremely important when these monosleds are used. Overcorrection of the leg axis
      is generally avoided. The use of too-high medial onlays is also reliably avoided
      by the navigation system's monitoring of the level of the cut.

PMID- 16969644
TI  - Induction of the chemokine interferon-gamma-inducible protein-10 in human
      pancreatic islets during enterovirus infection.
AB  - AIMS/HYPOTHESIS: Enterovirus infections have long been suspected to be
      environmental factors that may cause type 1 diabetes, but the pathways leading
      from infection to beta cell destruction are still unknown. We therefore examined
      whether enterovirus infection of human islets leads to upregulation of interferon
      gamma-inducible protein (IP-10, now known as chemokine [C-X-C motif] ligand 10
      [CXCL10]), a chemokine important for the induction of insulitis. METHODS:
      Isolated human islets were infected with three different strains of Coxsackie B4
      virus. IP-10 expression and secretion from the infected human islets were then
      measured using RT-PCR and ELISA at several time points. RESULTS: IP-10 was
      clearly upregulated in and secreted from human islets during enterovirus
      infection. This was demonstrated with three different strains of Coxsackie B4
      virus, two of which are lytic to islets and one which is non-lytic and can
      establish a persistent infection in human islets. CONCLUSIONS/INTERPRETATION: We
      propose that enterovirus-induced upregulation of IP-10 during infection of the
      islets in vivo is the first step towards destructive insulitis. Our findings
      support the idea that enterovirus infection triggers immune-mediated beta cell
      destruction, and for the first time suggest a possible mechanism behind
      enterovirus-induced diabetes.

PMID- 16969645
TI  - Three-year increase of gamma-glutamyltransferase level and development of type 2
      diabetes in middle-aged men and women: the D.E.S.I.R. cohort.
AB  - AIMS/HYPOTHESIS: Among hepatic markers, gamma-glutamyltransferase (GGT) is the
      main predictor for development of type 2 diabetes, but there are no data to date
      on changes in GGT and type 2 diabetes incidence. METHODS: Data at baseline and at
      3 years from the D.E.S.I.R. cohort were used, comprising 2,071 men and 2,130
      women without baseline diabetes. RESULTS: Changes in GGT level were correlated
      with changes in markers of insulin resistance (fasting insulin, homeostasis model
      assessment of insulin resistance), as well as with the following elements of the
      metabolic syndrome: central obesity, and increased fasting glucose, triglycerides
      and blood pressure (systolic and diastolic). The 3-year increase in GGT was
      associated with incident type 2 diabetes in both sexes, after adjusting for age
      and baseline GGT. After further adjustment for baseline confounding factors,
      including alanine-aminotransferase, alcohol intake, obesity and fasting insulin,
      the odds ratios (95% CI) for an association between incident type 2 diabetes and
      unchanged or increased (as opposed to decreased) GGT levels were 2.54 (1.38-4.68)
      in men (p=0.003) and 2.78 (1.20-6.42) in women (p=0.02). These associations were
      slightly attenuated after adjusting for the 3-year change in BMI, alcohol
      consumption and fasting insulin, the odds ratios being 2.49 (1.28-4.86) in men
      and 2.53 (1.01-6.40) in women. This relationship was not dependent on intra
      individual variability. CONCLUSIONS/INTERPRETATION: An unchanged or increased GGT
      level over time, even when GGT is in the normal range, is correlated with
      increasing insulin resistance and is associated with a risk of incident type 2
      diabetes in both sexes, independently of baseline GGT, which is itself a diabetes
      risk factor.

PMID- 16969646
TI  - The -374 T/A polymorphism in the gene encoding RAGE is associated with diabetic
      nephropathy and retinopathy in type 1 diabetic patients.
AB  - AIMS/HYPOTHESIS: The receptor for AGE (RAGE) is considered to be mainly an
      intracellular signal-transducer or pro-inflammatory peptide of possible
      importance for inflammation and autoimmune diseases. Our aim was to study whether
      the -374 T/A polymorphism in the gene encoding RAGE (AGER) is associated with
      diabetes type and presence of diabetic complications. METHODS: The AGER -374 T/A
      polymorphism was genotyped in 867 type 1 diabetic patients, 2,467 type 2 diabetic
      patients and 205 non-diabetic control subjects of Scandinavian origin. RESULTS:
      AGER polymorphism was related to different HLA-DQB1 genotypes and the presence of
      diabetic complications. Type 1 diabetic patients had a higher frequency of the
      AGER -374 A/A or T/A genotypes than type 2 diabetic patients (51.1 vs 44.9%,
      p=0.002) and control subjects (51.1 vs 47.6%, p=0.0006). The RAGE -374 T/A
      polymorphism was associated with HLA-DQB1 genotypes; patients with HLA risk
      genotypes had a higher frequency of the A/A or T/A genotypes than patients with
      other HLA-DQB1 genotypes (60.3 vs 40.3%, p<0.000001). In type 1 diabetic
      patients, the frequency of the A/A or T/A genotypes was higher in patients with
      diabetic nephropathy than without (61.1 vs 46.8%, p=0.006) and with sight
      threatening retinopathy than without (56.1 vs 47.6%, p=0.03). In type 2 diabetic
      patients with HbA(1c) values below the median, the T/T genotype was more frequent
      in patients with diabetic nephropathy than without (54.3 vs 38.2%, p=0.02).
      CONCLUSIONS/INTERPRETATION: Our results show an association between the AGER -374
      T/A polymorphism and type 1 diabetes. This association was HLA-DQB1-dependent.
      The polymorphism was associated with diabetic nephropathy in both type 1 and type
      2 diabetes, in an HbA(1c)-dependent manner in the latter group, and also with
      sight-threatening retinopathy in type 1 diabetic patients.

PMID- 16969647
TI  - The impact of family history of diabetes and lifestyle factors on abnormal
      glucose regulation in middle-aged Swedish men and women.
AB  - AIMS/HYPOTHESIS: We investigated associations between abnormal glucose regulation
      and family history of diabetes, separately and in combination with lifestyle risk
      factors. SUBJECTS AND METHODS: This cross-sectional study comprised 3,128 men and
      4,821 women, aged 35-56 years, half with a family history of diabetes. Oral
      glucose tolerance testing identified subjects with previously undiagnosed
      prediabetes (IFG, IGT) and type 2 diabetes. Information on lifestyle factors was
      obtained by questionnaire. Biological interaction was measured with the synergy
      index. RESULTS: A family history of diabetes conferred a higher odds ratio (OR)
      for type 2 diabetes in men (OR=3.1, 95% CI 1.7-5.6) than in women (OR=1.7, 95% CI
      1.0-3.0), and the synergy index was 2.8 (95% CI 0.9-9.0), suggesting interaction
      between a family history of diabetes and sex. For prediabetes and diabetes
      combined, the synergy index was 1.7 (1.0-2.8). Exposure to only one lifestyle
      risk factor (obesity, physical inactivity, smoking or low sense of coherence [a
      psychosocial index]) increased the risk to a similar extent in men and women.
      Combined exposure to a family history of diabetes and lifestyle-related risk
      factors had a greater effect on type 2 diabetes than any of these factors alone,
      especially in men. However, analysis of interaction between a family history of
      diabetes and the lifestyle factors did not indicate any interaction for diabetes,
      but did indicate interaction for a family history of diabetes and obesity in
      women with prediabetes. CONCLUSIONS/INTERPRETATION: Our data suggest a more
      pronounced effect of a family history of diabetes on the risk of type 2 diabetes
      in men than in women. While both a family history of diabetes and lifestyle risk
      factors had effects on type 2 diabetes, irrespective of sex, these effects did
      not appear to interact.

PMID- 16969648
TI  - Sympathetic nerve hyperactivity in non-diabetic offspring of patients with type 2
      diabetes mellitus.
AB  - AIMS/HYPOTHESIS: Type 2 diabetes mellitus with hyperinsulinaemia is a state of
      sympathetic nerve hyperactivity, which can develop subsequently in non-diabetic
      first-degree offspring of patients with type 2 diabetes. Although both type 2
      diabetes and sympathetic activation are major cardiovascular risk factors, the
      level of sympathetic nerve activity is as yet unknown in offspring of type 2
      diabetic patients who are ostensibly normal. We therefore sought to quantify
      sympathetic nerve activity and its relationship to plasma insulin levels in
      ostensibly normal offspring of patients with type 2 diabetes, relative to a
      matched normal control group with no family history of type 2 diabetes. SUBJECTS
      AND METHODS: In two closely matched groups comprising 23 non-diabetic offspring
      of type 2 diabetic patients and 23 normal control individuals we measured resting
      muscle sympathetic nerve activity (MSNA) as the mean frequency of multi-unit
      bursts of MSNA and single units of MSNA (s-MSNA) with defined vasoconstrictor
      properties. RESULTS: In offspring of type 2 diabetic patients, the fasting plasma
      levels of insulin (7.4+/-0.80 microU/ml) and s-MSNA (45+/-3.2 impulses/100 beats)
      were greater (p<0.009 and p<0.003) than those in control persons (4.6+/-0.76
      microU/ml and 32+/-3.1 impulses/100 beats, respectively). MSNA bursts and derived
      insulin resistance followed similar trends. Sympathetic nerve activity was
      significantly correlated to insulin levels (p<0.0002) and resistance (p<0.0001)
      in offspring of type 2 diabetic patients, but not in control subjects.
      CONCLUSIONS/INTERPRETATION: Sympathetic activation occurred in normal non
      diabetic offspring of patients with type 2 diabetes in proportion to their plasma
      insulin levels. Our data indicate the presence of a mechanistic link between
      hyperinsulinaemia and sympathetic activation, both of which could play a role in
      the subsequent development of cardiovascular risk factors.

PMID- 16969649
TI  - Association between serum levels of soluble receptor for advanced glycation end
      products and circulating advanced glycation end products in type 2 diabetes.
AB  - AIMS/HYPOTHESIS: Activation of the receptor for advanced glycation end products
      (RAGE, also known as AGE-specific receptor [AGER]) has been implicated in the
      development of diabetic vascular complications. Blockade of RAGE using a soluble
      form of the receptor (sRAGE) suppressed vascular hyperpermeability and
      atherosclerosis in animal models. Since little is known about the regulation of
      endogenous sRAGE levels, we determined whether serum sRAGE is influenced by
      circulating AGEs and the severity of nephropathy in type 2 diabetic patients.
      MATERIALS AND METHODS: We recruited 150 healthy control and 318 diabetic
      subjects. Diabetic subjects were subdivided into those with proteinuria,
      microalbuminuria or normoalbuminuria. Serum sRAGE was assayed by ELISA and serum
      AGEs by competitive ELISA using a polyclonal rabbit antiserum raised against AGE
      RNase. RESULTS: Diabetic subjects had higher sRAGE (1,029.5 pg/ml [766.1-1,423.0]
      interquartile range vs 1,002.6 [726.5-1,345.3], p<0.05) and AGEs (4.07+/-1.13,
      SD, unit/ml vs 3.39+/-1.05, p<0.01) than controls. Proteinuric subjects had the
      highest sRAGE levels and there was a significant trend between the severity of
      nephropathy and sRAGE (p=0.01). In diabetic subjects, serum log(sRAGE) correlated
      with AGEs (r=0.27, p<0.001), log(plasma creatinine) (r=0.31, p<0.001), log(urine
      AER) (r=0.24, p<0.01) and log(triglycerides) (r=0.15, p<0.01). On stepwise linear
      regression analysis, AGEs and creatinine levels were the main independent
      determinants of sRAGE concentration. CONCLUSIONS/INTERPRETATION: Serum sRAGE
      levels and circulating AGEs are associated with the severity of nephropathy in
      type 2 diabetic patients. Prospective studies are required to determine whether
      endogenous sRAGE potentially influences the development of diabetic vascular
      complications.

PMID- 16969650
TI  - [What do head physicians want? Current state of bringing together orthopedics and
      accident surgery].

PMID- 16969651
TI  - [Distal radius fracture. Correlation between radiological and functional
      results].
AB  - BACKGROUND: The purpose of the present study was to investigate the influence of
      the radiological parameters on the functional outcome of patients with a fracture
      of the distal radius and to find out to which extent a deformity can be
      tolerated. PATIENTS AND METHODS: A total of 344 patients with an isolated
      fracture of the distal radius were treated during a 3-year period; 211 of them
      were evaluated at an average of 16 months after the accident according to the
      score of Gartland and Werley as modified by Sarmiento. Furthermore, we developed
      our own score for evaluating the influence of radiological parameters on the
      functional outcome. RESULTS: According to the AO classification, there were 20
      patients with an A2, 71 an A3, 11 a B, 35 a C1, 44 a C2, and 30 a C3 fracture. Of
      211 patients, 28 (13%) had a step-off in the articular surface of over 1 mm,
      resulting in a 24% reduction of the range of motion compared to the non-injured
      wrist (p<0.05). Patients with a radial shortening of more than 3 mm (n=12) had a
      21% reduction of pro- and supination compared to the non-injured side (p<0.05).
      The radial tilt and the palmar inclination did not have a direct influence on the
      functional outcome. Patients treated with K-wire pinning and with an initial
      palmar inclination of less then -15 degrees had a significantly higher secondary
      loss of palmar inclination of 9 degrees compared to all others (p<0.05) at the
      final follow-up. CONCLUSION: The main radiological factors influencing the
      functional outcome of fractures of the distal radius are radial shortening and a
      step-off in the articular surface.

PMID- 16969652
TI  - [White book of severely injured - care of the DGU. Recommendations on structure,
      organization and provision of hospital equipment for care of severely injured in
      the Federal Republic of Germany].

PMID- 16969653
TI  - [Temporary percutaneous spondylodesis C1/2 and halo vest immobilisation. An
      alternative treatment of complex injuries of the upper cervical spine].
AB  - Dislocated combined injuries of the upper cervical spine such as C 1/2 fractures
      require occipitocervical fusion, especially if the dislocation can not be
      redressed using halo vest immobilisition. We report on the clinical course and
      outcome of a young woman who sustained complex cervical spine injuries. Closed
      reduction and a percutaneous transfixation of C 1/2 with k-wires (Magerl) and an
      additional halo vest immobilisition was performed to avoid permanent fusion. The
      25 year old patient was involved in a motor vehicle accident that resulted in a
      dislocated Jefferson's fracture, an odontoid fracture type II (Anderson and
      d'Alonso) with protrusion into the foramen magnum, and a dislocated C 6/7
      fracture. A ventral spondylodesis C6/7 was followed by temporary dorsal
      spondylodesis C1/2 with k-wires (Magerl) and additional halo vest immobilisition
      after closed reduction. The temporary percutaneous fixation C1/2 was removed
      after 11 weeks, as was the halo vest immobilisition. After removing the temporary
      percutaneous fixation (k-wires) and the halo system, the patient showed very good
      functional results in terms of range of motion with only minor discomfort.
      Complex injuries of the upper cervical spine that cannot be retained by external
      fixation often require an occipitocervical fusion or fixation of C1/2. In the
      case presented, the temporary percutaneous fixation (Magerl) with k-wires was
      terminated after 3 months to avoid significant functional impairment. Younger
      patients benefit most from temporary fusion of the upper cervical spine, which
      results in better functional outcome and only minor pain.

PMID- 16969654
TI  - [Ulnar nerve lesions after osteosynthesis of a supercondylar humerus fracture
      during childhood. Indications for revision].
AB  - Since 1948, closed reduction and osteosynthesis for supracondylar humeral
      fractures using two K-wires from the medial and lateral side has been performed
      on a regular basis. Although this procedure is used routinely, many authors have
      described paralysis of the ulnar nerve after blindly inserting the medial K-wire.
      Only very few publications describe the treatment options after iatrogenic
      paralysis of this nerve. The patients described showed progressive paralysis of
      the ulnar nerve after K-wire osteosynthesis. Intraoperatively, all patients
      showed scarring but intact continuity. After surgical revision and neurolysis,
      all four patients showed complete restitution after 1 year. If patients show
      progressive paralysis of the ulnar nerve early operative revision after 3 months
      should be performed.

PMID- 16969656
TI  - Accelerated acquisition of permeability barrier function in the skin of
      presenilin-1-deficient embryos.
AB  - Presenilin-1 (PS1) is a transmembrane protein and is responsible for the
      development of early-onset familial Alzheimer's disease. PS1 is essential for
      neurogenesis, somitogenesis, angiogenesis and cardiac morphogenesis. We report
      here that PS1 is involved in the development of skin barrier function. PS1
      deficient embryos showed an accelerated acquisition of permeability barrier
      function at embryonic day 17.5 as manifested by the exclusion of a dye solution.
      While the expression of beta-catenin and epidermal differentiation markers such
      as keratin 1 and loricrin was not substantially altered, an increased
      accumulation of E-cadherin was observed immunohistochemically in the mutant skin.
      These results suggest that PS1 regulates the acquisition of permeability barrier
      function in the skin.

PMID- 16969655
TI  - [Candida albicans induced spondylodiscitis of the cervical spine of a
      polytraumatized patient].
AB  - With the increasing occurrence of predisposing factors, invasive candidiasis is
      being diagnosed more frequently. Based on a review of only a few previous
      reported cases, we describe and discuss the unusual case of candidal cervical
      spondylodiscitis in a 36 year old man who had sustained a polytrauma, complicated
      through a Candida albicans pneumonia. The main symptom was disabling neck pain.
      Clinical, laboratory and radiological findings were unspecific. The definitive
      diagnosis was determined by MRI imaging and biopsy. The early diagnosis and
      surgical treatment with a sufficient debridement and stabilisation of the
      affected segment combined with a prolonged antifungal therapy lead to good
      results.

PMID- 16969657
TI  - Clinical evaluation of chemomechanical and mechanical caries removal: status of
      the restorations at 3, 6, 9 and 12 months.
AB  - In this study, the clinical efficacy of Carisolvtrade mark system and the hand
      excavation method in the removal of occlusal dentine caries of primary molar
      teeth was evaluated. Both Carisolv system and hand excavation method were applied
      for the removal of caries on different teeth of the same children. After the
      removal of the caries, Dyract AP materials were used to restore the teeth. The
      clinical follow-up was made every 3 months within a year. The clinical
      evaluations of restorations were carried out in accordance with US Public Health
      Service (USPHS) criteria. To determine whether there was any statistical
      difference between the groups, chi-square analysis was used. During both
      excavation methods, pain occurrence and the need for anesthesia and the time
      spent were all recorded. The time spent for the removal of caries in Carisolv
      system and in hand excavation method was 9.03+/-4.14 min (mean+/-SD) and 7.34+/
      3.41 min (mean+/-SD), respectively (P>0.05). At the end of 1 year, differences
      between Carisolv and hand excavation groups in terms of marginal adaptation and
      secondary caries were found to be statistically insignificant (P>0.05). During
      the removal of caries, certain children complained about pain both in Carisolv
      system and hand excavation method (7.1 and 35.7%, respectively). As a result, it
      can be argued that Carisolv system is effective in the removal of caries and
      causes minimum level pain occurrence. Compared to hand excavation, Carisolv
      system seems to be a promising restorative approach to remove occlusal caries in
      primary molar teeth. Studies of longer duration are needed to confirm these
      findings.

PMID- 16969658
TI  - Influence of ascorbic acid on bonding of peroxide-affected dentin and 4-META/MMA
      TBB resin.
AB  - The purpose of this study was to evaluate the tensile bond strength (TBS) to
      peroxide-exposed dentin. Furthermore, the effect of ascorbic acid (AA) on the
      bond strength of peroxide-exposed dentin was investigated. Extracted bovine
      dentin was exposed to 10% carbamide peroxide, 30% hydrogen peroxide, or distilled
      water for 30 min, then treated with 10% AA (0, 30, 90, and 180 min), and
      conditioned with 10% citric acid/3% ferric chloride. The polymethyl-methacrylate
      (PMMA) rod was bonded to the treated bovine dentin with 4-META/MMA-TBB resin. A
      minidumbbell-shaped bonded specimen was prepared from these bonded assemblies and
      the TBS was tested. The fractured surfaces were also observed with a scanning
      electron microscope. Exposure to peroxide before bonding significantly reduced
      bond strength. The application of AA to the peroxide-exposed dentin increased
      bond strength. On the other hand, an adverse effect of AA was found in distilled
      water-affected dentin. Extended resin fibers were partially seen in the peroxide
      exposed dentin. In conclusion, peroxide reduced the bond strength, and the
      stronger the oxidation, the weaker the obtained bond. Antioxidation with AA
      recovered the bond strength, and this effect increased the longer the AA was
      applied.

PMID- 16969659
TI  - Nonsurgical treatment of moderate and advanced periimplantitis lesions: a
      controlled clinical study.
AB  - The aim of this controlled, parallel design clinical study was to evaluate the
      effectiveness of an Er:YAG (erbium-doped:yttrium, aluminum, and garnet) laser for
      nonsurgical treatment of periimplantitis lesions. Twenty patients, each of whom
      displayed at least one implant with (a) moderate and (b) advanced periimplantitis
      (n=40 implants; IMZ, ITI, Spline Twist, ZL-Duraplant, Camlog), were randomly
      instrumented nonsurgically using either (1) an Er:YAG laser (100 mJ/pulse, 10 Hz)
      device (LAS) or (2) mechanical debridement using plastic curettes and antiseptic
      therapy with chlorhexidine digluconate (0.2%) (C). The following clinical
      parameters were measured at baseline, 3, 6, and 12 months after treatment: plaque
      index, bleeding on probing (BOP), probing depth, gingival recession, and clinical
      attachment level (CAL). Mean BOP improved significantly in both groups at 3, 6,
      and 12 months (a- lesions: P<0.001 and b- lesions: P<0.01, respectively). After 3
      and 6 months, the mean reduction of BOP was significantly higher in the LAS group
      when compared to the C group (a- and b- lesions: P<0.01 and P<0.05,
      respectively). At 3 and 6 months, both groups revealed significant CAL gains at a
      and b- lesions (P<0.01, respectively). In both groups, however, the mean CAL at
      a- and b- lesions was not significantly different from the respective baseline
      values at 12 months (P>0.05, respectively). Although treatment of periimplantitis
      lesions with LAS resulted in a significantly higher BOP reduction than C, its
      effectiveness seemed to be limited to a period of 6 months, particularly at b-
      lesions.

PMID- 16969660
TI  - [Ileus disease].
AB  - Intestinal obstruction may be mechanical or non-mechanical (adynamic ileus).
      Adhesions and external hernias are the most common causes of obstruction in small
      intestine, whereas carcinoma, sigmoid diverticulitis, and volvulus are the most
      common causes in large intestine obstruction. Distension of the intestine caused
      by gas and fluid accumulation in the obstructed segment is the key
      pathophysiological mechanism initiating ileus with subsequent multiorgan failure
      and death. Surgery should always be undertaken if complete obstruction or
      strangulation is suggested and ileus is established. Before operation, the fluid
      and electrolyte balance should be restored and decompression instituted by means
      of a nasogastric tube. Delaying the operation because of improvement in patient
      well-being during resuscitation is only justified in those suffering from large
      intestine obstruction due to colorectal carcinoma. Purely nonoperative treatment
      is safe only in the presence of incomplete obstruction and best utilized in
      patients with postoperative adynamic ileus or repeated episodes of partial
      obstruction.

PMID- 16969661
TI  - Osteoarthritis of the knee in the young and active.

PMID- 16969662
TI  - Global comparative transcriptome analysis identifies gene network regulating
      secondary xylem development in Arabidopsis thaliana.
AB  - Our knowledge of the genetic control of wood formation (i.e., secondary growth)
      is limited. Here, we present a novel approach to unraveling the gene network
      regulating secondary xylem development in Arabidopsis, which incorporates
      complementary platforms of comparative-transcriptome analyses such as "digital
      northern" and "digital in situ" analysis. This approach effectively eliminated
      any genes that are expressed in either non-stem tissues/organs ("digital
      northern") or phloem and non-vascular regions ("digital in situ"), thereby
      identifying 52 genes that are upregulated only in the xylem cells of secondary
      growth tissues as "core xylem gene set". The proteins encoded by this gene set
      participate in signal transduction, transcriptional regulation, cell wall
      metabolism, and unknown functions. Five of the seven signal transduction-related
      genes represented in the core xylem gene set encode the essential components of
      ROP (Rho-related GTPase from plants) signaling cascade. Furthermore, the analysis
      of promoter sequences of the core xylem gene set identified a novel cis
      regulatory element, ACAAAGAA. The functional significances of this gene set were
      verified by several independent experimental and bioinformatics methods.

PMID- 16969663
TI  - Multifocal gastrointestinal stromal tumor (GIST) of the stomach in an 11-year-old
      girl.
AB  - A previously healthy 11-year-old girl presented with an 8-month history of anemia
      and left upper quadrant abdominal pain. US examination demonstrated a 9-cm cystic
      mass with a fluid-fluid level in the left upper quadrant with unclear organ of
      origin. Abdominal MR imaging demonstrated a complex cystic mass, likely arising
      from the stomach. Additional T2 hyperintense submucosal lesions were identified
      in the gastric wall. Surgical excision confirmed the diagnosis of multifocal
      gastric gastrointestinal stromal tumor (GIST). MR imaging was helpful in
      suggesting a gastric origin of the primary mass and in demonstrating multifocal
      disease within the stomach.

PMID- 16969666
TI  - Quantitative structure-activity relationships for prediction of the toxicity of
      hydroxylated and quinoid PCB metabolites.
AB  - Quantitative structure-activity relationship (QSAR) models were developed for the
      in vitro potencies to downregulate gap junctional intercellular communication
      (GJIC) of hydroxylated polychlorinated biphenyls (OH-PCBs) and PCB quinines using
      partial least squares (PLS) regression. Quantum chemical descriptors computed by
      the semiempirical AM1, PM3 and MNDO methods were used as predictor variables. The
      cross-validated Q2cum values for the three optimal QSAR models are 0.784, 0.789
      and 0.755, respectively, indicating good predictive capabilities for the acute
      inhibition of GJIC (IC(50)) of oxygenated PCB derivatives. The slightly higher
      Q2cum value of the model using computed molecular descriptors from the PM3
      Hamiltonian suggested a slightly better predictive power than the models
      developed using AM1 or MNDO. However, given these dispersion parameters in these
      three optimal models, there would not be a significant difference between the
      Q2cum values. Results from this study showed that the logarithmic scale of IC(50)
      is affected by different molecular structural descriptors.

PMID- 16969667
TI  - Fundamental measure theory of hydrated hydrocarbons.
AB  - To calculate the solvation of hydrophobic solutes, we have developed a method
      based on the fundamental measure treatment of density functional theory. This
      method allows us to carry out calculations of density profiles and the solvation
      energy for various hydrophobic molecules with high accuracy. We have applied the
      method to the hydration of various hydrocarbons (linear, branched and cyclic).
      The calculations of the entropic and enthalpic parts are also carried out. We
      have examined the question of the temperature dependence of the entropy
      convergence. Finally, we have calculated the mean force potential between two
      large hydrophobic nanoparticles immersed in water.

PMID- 16969668
TI  - Molecular docking studies on 4-thiazolidinones as HIV-1 RT inhibitors.
AB  - Flexible docking simulations were performed on two series of 4-thiazolidinones as
      HIV-1 reverse transcriptase (HIV-1 RT) inhibitors. This was done by analyzing the
      interaction of these compounds with the allosteric site of the HIV-1 reverse
      transcriptase enzyme. The binding scores for these compounds were also congruent
      with their anti-HIV activity. A good correlation between the predicted binding
      free energies and the experimentally observed inhibitory activities (EC(50))
      suggest that the identified binding conformations of these inhibitors are
      reliable. The results of docking studies provide an insight into the
      pharmacophoric structural requirements for the HIV-1 RT inhibitory activity of
      this class of molecules.

PMID- 16969670
TI  - [Fatigue and icterus in a 27-year-old patient with diabetes mellitus type I].
AB  - We report about a 27-year-old female with type I diabetes who was admitted with
      progressive fatigue and a sudden onset of icterus. As the underlying cause, we
      found pernicious anemia with hemolytic activity as part of polyglandular
      autoimmune syndrome (PAS) type II. Under vitamin B(12) substitution we saw a
      quick rise in hemoglobin and improvement of complaints. Type I diabetes is the
      most frequent component of PAS II, whereas pernicious anemia is a rather rare
      component; however, a latent form is seen in about 12% of patients with type I
      diabetes. Therapy for pernicious anemia consists of parenteral vitamin B(12)
      substitution. Because of an increased incidence of gastric cancer in chronic
      atrophic gastritis, endoscopic follow-ups of the chronic atrophic autoimmune
      gastritis seem to be recommended. Due to the diverse characteristic of PAS II,
      with development of additional components after years of latency, regular follow
      up clinical examinations and lab work are mandatory to detect further need of
      hormone and vitamin replacement that may sometimes be substantial for survival.

PMID- 16969669
TI  - Characterization of a HoxEFUYH type of [NiFe] hydrogenase from Allochromatium
      vinosum and some EPR and IR properties of the hydrogenase module.
AB  - A soluble hydrogenase from Allochromatium vinosum was purified. It consisted of a
      large (M (r) = 52 kDa) and a small (M (r) = 23 kDa) subunit. The genes encoding
      for both subunits were identified. They belong to an open reading frame where
      they are preceded by three more genes. A DNA fragment containing all five genes
      was cloned and sequenced. The deduced amino acid sequences of the products
      characterized the complex as a member of the HoxEFUYH type of [NiFe]
      hydrogenases. Detailed sequence analyses revealed binding sites for eight Fe-S
      clusters, three [2Fe-2S] clusters and five [4Fe-4S] clusters, six of which are
      also present in homologous subunits of [FeFe] hydrogenases and NADH:ubiquione
      oxidoreductases (complex I). This makes the HoxEFUYH type of hydrogenases the one
      that is evolutionary closest to complex I. The relative positions of six of the
      potential Fe-S clusters are predicted on the basis of the X-ray structures of the
      Clostridium pasteurianum [FeFe] hydrogenase I and the hydrophilic domain of
      complex I from Thermus thermophilus. Although the HoxF subunit contains binding
      sites for flavin mononucleotide and NAD(H), cell-free extracts of A. vinosum did
      not catalyse a H(2)-dependent reduction of NAD(+). Only the hydrogenase module
      (HoxYH) could be purified. Its electron paramagnetic resonance (EPR) and IR
      spectral properties showed the presence of a Ni-Fe active site and a [4Fe-4S]
      cluster. Its activity was sensitive to carbon monoxide. No EPR signals from a
      light-sensitive Ni(a)-C* state could be observed. This study presents the first
      IR spectroscopic data on the HoxYH module of a HoxEFUYH type of [NiFe]
      hydrogenase.

PMID- 16969671
TI  - [Ventricular tachycardia. Diagnostic spectrum and therapeutic measures].
AB  - The origin of ventricular tachycardia lies in the ventricular tissue and includes
      a variety of symptoms such as monomorphic and polymorphic ventricular
      tachyarrhythmia (VT), ventricular flutter and ventricular fibrillation. Due to
      transitions of one form of VT to another, any form of VT incurs in principal the
      risk of cardiac failure. Apart from different electrophysiologic mechanisms such
      as reentry or triggered activity, any occurrence of VT has to be considered in an
      individual context: VT can be caused by structural heart disease such as coronary
      artery disease or dilative cardiomyopathy, or primary electrical disease such as
      long or short QT syndromes or can even occur without any detectable cause
      (idiopathic VT). Correct identification of the underlying cause of the arrhythmia
      is essential for the prognosis, differential therapy and long-term treatment of
      patients.

PMID- 16969672
TI  - Utility of fat-suppressed FLAIR and subtraction imaging in detecting meningeal
      abnormalities.
AB  - We describe the use of a combination of fat-suppression SPIR (spectral inversion
      recovery) and subtraction FLAIR imaging to aid in detection of abnormal meningeal
      enhancement.

PMID- 16969673
TI  - Endovascular treatment of direct carotid cavernous fistulae: a pictorial review.
AB  - INTRODUCTION: Direct carotid-cavernous fistulae (CCFs) are type A fistulae
      according to Barrow's classification. Endovascular treatment of these lesions is
      challenging. METHODS: The purpose of this review was to evaluate the endovascular
      treatment of direct CCFs. We also describe the technique, symptomatology and
      complications associated with the procedure and report on the long-term follow-up
      in our treated patients. RESULTS: A total of 89 patients with a direct CCF were
      treated. All patients had baseline brain CT or MR imaging. Treatment comprised
      transarterial balloon or coil embolizations. The patients were followed up at 1
      month and then every 6 months thereafter. Detachable balloons were used in 79
      fistulae. In 12 fistulae the balloon could not be negotiated through the fistula
      and these fistulae were treated with transarterial coil occlusion. Clinical
      outcomes of the treated patients evaluated at 1 month were: 79 patients (88.8%)
      cured, 9 (10.1%) significantly improved, 1 (1.1%) remaining static. CONCLUSION:
      Endovascular treatment of direct CCFs is safe and effective and results in long
      term cure.

PMID- 16969675
TI  - Stage-related changes in functional capacity in Hodgkin's disease: assessment by
      cardiopulmonary exercise testing before initiation of treatment.
AB  - Our aim was to examine indices of cardiorespiratory capacity at rest and during
      exercise before initiation of therapy for Hodgkin's disease. We prospectively
      studied 24 patients divided into two groups according to the disease stage. Group
      1 included eight patients in stage IA and four in stage IIA; group 2 included
      four patients in stage IIB, six in stage III, and two in stage IV. All patients
      underwent detailed cardiopulmonary evaluations at rest using electrocardiogram,
      echocardiogram, spirometry, and measurement of pulmonary diffusing capacity
      (DLCO), and during exercise using a cardiopulmonary exercise test. Groups 1 and 2
      were similar with respect to sex distribution (eight women and four men in each),
      mean age (35+/-36 vs37+/-4.6 years), body mass index, and hemoglobin
      concentration (12.7+/-0.2 vs 12.1+/-0.3 g l-1). All patients had a normal
      cardiovascular status. All patients in group 1 had normal cardiorespiratory
      measurements at rest and during exercise. Forced vital capacity was significantly
      lower in group 2 (84.8+/-2.7% predicted) than in group 1 (105+/-3%, P<0.0001),
      without abnormalities in DLCO or in resting and exercise oxygen diffusion.
      Likewise, percentage predicted VO2max (65+/-4 vs 97+/-6, P<0.0002), oxygen pulse
      at peak exercise (0.12+/-0.01 vs 0.17+/-0.01, P<0.001), and DeltaVO2/DeltaW slope
      (8.4+/-0.3 vs 10.2+/-0.4, P<0.003) were significantly lower in group 2 than in
      group 1. Functional capacity during exercise was markedly reduced in patients
      suffering from Hodgkin's disease in advanced stages. This loss of exercise
      capacity appeared mainly related to a peripheral disorder.

PMID- 16969674
TI  - [Cluster immunotherapy in allergic rhinoconjunctivitis: review of a new
      therapeutic approach].
AB  - Apart from allergen avoidance, specific immunotherapy (SIT) represents the only
      potentially curative treatment available to patients with allergic
      rhinoconjunctivitis. Evidence for its clinical efficacy has been clearly
      demonstrated in several controlled clinical trials and depends on the allergen to
      which the patient is sensitive, the quality and total amount of allergen
      administered, and the SIT schedule. In classic SIT, gradually ascending dosages
      of the allergen extract are injected subcutaneously (dose-increase period) until
      the individual maximum dose is reached (dose-maintenance period). Several dosage
      schedules have been worked out. In cluster immunotherapy, 2-3 injections per day
      of treatment are given once a week to rapidly reach the maintenance dose. Several
      cluster schedules have been described. Recent data demonstrate that the frequency
      and severity of adverse effects in cluster immunotherapy correspond to those in
      other dosage schedules. As far as safety goes, cluster immunotherapy is an
      interesting alternative for the dose-increase period. In addition, recent studies
      reveal that clinical benefits appear sooner with cluster immunotherapy.

PMID- 16969676
TI  - Stumbling with optimal phase reset during gait can prevent a humanoid from
      falling.
AB  - The human biped walking shows phase- dependent transient changes in gait
      trajectory in response to external brief force perturbations. Such responses,
      referred to as the stumbling reactions, are usually accompanied with phase reset
      of the walking rhythm. Our previous studies provided evidence, based on a human
      gait experiment and analyses of mathematical models of gait in the sagittal
      plane, that an appropriate amount of phase reset in response to a perturbation
      depended on the gait phase at the perturbation and could play an important role
      for preventing the walker from a fall, thus increasing gait stability. In this
      paper, we provide a further material that supports this evidence by a gait
      experiment on a biped humanoid. In the experiment, the impulsive force
      perturbations were applied using push-impacts by a pendulum-like hammer to the
      back of the robot during gait. The responses of the external perturbations were
      managed by resetting the gait phase with different delays or advancements. The
      results showed that appropriate amounts of phase resetting contributed to the
      avoidance of falling against the perturbation during the three-dimensional robot
      gait. A parallelism with human gait stumbling reactions was discussed.

PMID- 16969677
TI  - On the variety of cell death pathways in the Lurcher mutant mouse.
AB  - Apoptosis as well as autophagy have been implicated in the death of cerebellar
      Purkinje cells (PCs) in the Lurcher (Lc/+) mutant mouse and at least two
      different apoptotic pathways participate in the transsynaptic death of granule
      cells (GC) and inferior olivary (IO) neurones. The relative contribution of these
      pathways can only be assessed from their momentary involvement at any stage of
      the complete course of neurodegeneration. Here we used quantitative labelling for
      activated caspase-3 (Casp-3) and Fluoro-Jade B (FJ-B) to investigate the spatio
      temporal pattern of neuronal death from P6 to P67 in Lc/+ mutants. Activated Casp
      3 was present only in narrow time intervals (P14 to P22 in PCs; P14 to P28 in
      GCs) and in small subpopulations of PCs, GCs, and IO neurones. FJ-B positive PCs
      were detected during a broader period (P14 to P28), and outnumbered Casp-3
      labelled PCs by a factor exceeding eight. Nevertheless, FJ-B labelling was
      restricted to PCs and never found in either GC or IO neurones. In conclusion, we
      present the first complete time course and extent of Casp-3 activation in Lc/+
      mutants and show that the majority of dying neurones in Lc/+ mutants undergo Casp
      3 independent cell death. The cellular overload produced by the initial gene
      defect in Lc/+ mutants apparently activates a variety of apoptotic and non
      apoptotic pathways within the same neuronal population. Moreover, we present the
      first evidence for the ability of FJ-B to selectively label a discrete population
      of dying PCs, implying a higher selectivity of FJ-B than previously supposed.

PMID- 16969678
TI  - A systematic review of the function and complications of colonic pouches.
AB  - PURPOSE: This is a meta-analysis of randomized, controlled trials to compare the
      function and complications of a straight coloanal anastomosis to a colonic J
      pouch after rectal excision at 1 year postoperatively. MATERIALS AND METHODS: A
      search for articles from 1980 to 2005 was conducted on Medline, PubMed, and the
      Cochrane Controlled Trials Register using the keywords "colonic pouches, J-pouch,
      straight and coloanal anastomosis, rectal cancer, function and complications,"
      either singularly or in combination. Reference lists from short-listed articles
      were also manually searched for relevant articles, journals, and conference
      proceedings. Randomized controlled trials (RCTs) in English publications
      comparing colonic J-pouches to straight coloanal anastomosis were selected.
      Trials with similar patient characteristics, duration of follow-up, and outcome
      measures were pooled for analysis. Stool frequency and fecal continence at 1 year
      postoperatively were used as measures of functional outcome. Complication rates
      in terms of anastomotic leak and stricture formation were analysed. RESULTS: Ten
      RCTs with satisfactory methodology were identified. One trial reported the
      results at 2 years, while another reported results at 5 years only and were
      excluded from the meta-analysis, leaving only eight studies for further analysis.
      Overall, a colonic J-pouch appeared more favorable in terms of stool frequency
      (weighted mean difference of -1.21, 95% CI: -1.92 to -0.49) and continence (Odds
      ratio 0.23, 95% CI: 0.08-0.69), with a slightly lower risk of anastomotic
      dehiscence compared to a straight coloanal anastomosis (relative risk, RR 0.36;
      95% CI: 0.12-1.08). Anastomotic stricture was reported in only two trials. They
      seemed more likely to occur after a pouch-anal anastomosis (RR 2.45, 95% CI: 0.79
      7.57). However, the small numbers available for pooled analysis cannot allow
      these conclusions to be drawn with confidence. CONCLUSIONS: A straight coloanal
      anastomosis resulted in poorer function due to loss of a rectal reservoir, while
      colonic J-pouches have improved frequency and continence up to a year. Although
      retrospective reports seem to favor the use of a pouch, there are limited longer
      term randomized trial data to suggest that the function and complications of a
      coloanal J-pouch is better than a straight coloanal anastomosis. Larger
      randomized studies are required to further verify the longer-term benefits of a
      coloanal pouch.

PMID- 16969679
TI  - Toll-like receptor 3 and TICAM genes in catfish: species-specific expression
      profiles following infection with Edwardsiella ictaluri.
AB  - Toll-like receptors (TLRs) are a family of transmembrane proteins that recognize
      specific pathogen-associated molecular patterns and use conserved signaling
      pathways to activate proinflammatory cytokines and type-1 interferons to fight
      infection. TLR3 in mammals is best known for its recognition of dsRNA as ligand
      and its MyD88-independent signaling. TLR3, upon recognition of dsRNA, recruits
      and binds its adaptor protein TIR domain-containing adapter molecule (TICAM) 1.
      Here we report the genomic sequences and structures of TLR3 and a TICAM adaptor
      from channel catfish (Ictalurus punctatus). Whereas a partial TLR3 cDNA sequence
      has been reported from channel catfish, and complete TLR3 genes are known from
      other teleost fish species, a complete TICAM sequence has not been previously
      reported from a nonmammalian species. Analysis of catfish TLR3 and TICAM
      expression after infection with Edwardsiella ictaluri, the causative agent of
      enteric septicemia of catfish (ESC), suggested a conserved TLR3-TICAM receptor
      adaptor relation in catfish. Comparison of TLR3 and TICAM expression profiles in
      channel catfish with those from the closely related blue catfish species
      (Ictalurus furcatus), which exhibits strong resistance to ESC, revealed a
      striking pattern of species-specific expression. A dramatic downregulation of
      TLR3 and TICAM gene expression was observed in blue catfish head kidney and
      spleen, which we speculate may be the result of maturation and migration of
      different cell types to and from the lymphoid tissues following infection.

PMID- 16969680
TI  - Efficacy of protocolized management for congenital diaphragmatic hernia. a review
      of 100 cases.
AB  - A review of 100 consecutive cases of congenital diaphragmatic hernia (CDH)
      treated at our institute focusing on the efficacy of protocolized management (PM)
      was conducted. Of the 100 cases, 14 who became symptomatic more than 24 h after
      birth, and seven with fatal anomalies (four cardiac and three chromosomal) were
      excluded, leaving 79 subjects for this study. Of these, 41 were diagnosed
      prenatally (PD). Subjects were divided into four groups. Group I: No PD, no PM (n
      = 34), Group II: No PD, PM (n = 4), Group III: PD, no PM (n = 21), and Group IV:
      PD, PM (n = 20). PM includes criteria for planned delivery, use of high frequency
      oxygenation, nitric oxide, echocardiography (EC), and a medication schedule.
      Overall survival rates for Groups I, II, III, and IV were 73.5% (25/34), 75%
      (3/4), 38.1% (8/21), and 70.0% (14/20), respectively. Survival rates were higher
      when PM was used: 70.8% (Groups II, IV) versus 60.0% (Groups I, III). Survival
      rates were significantly lower if diagnosed prenatally (PD+): 53.7% (Groups III,
      IV) versus 73.7% (Groups I, II) (P < 0.01). However, in PD+ groups, survival was
      significantly higher if PM was used (P < 0.05). PM significantly reduced length
      of hospital stay (35.5 vs. 52.0 days: P < 0.05). EC was found to be a predictor
      for survival while post-ductal AaDO(2) was not. In 17 cases with cardiac
      anomalies, PM did not affect survival. Our study suggests that use of PM for
      prenatally diagnosed CDH cases is associated with improved outcome, although the
      components of PM need to be tested in prospective trials to determine their true
      value.

PMID- 16969681
TI  - Mapping QTL for dollar spot resistance in creeping bentgrass (Agrostis
      stolonifera L.).
AB  - Dollar spot caused by Sclerotinia homoeocarpa F. T. Bennett is the most
      economically important turf disease on golf courses in North America. Dollar spot
      resistance in a creeping bentgrass cultivar would greatly reduce the frequency,
      costs, and environmental impacts of fungicide application. Little work has been
      done to understand the genetics of resistance to dollar spot in creeping
      bentgrass. Therefore, QTL analysis was used to determine the location, number and
      effects of genomic regions associated with dollar spot resistance in the field.
      To meet this objective, field inoculations using a single isolate were performed
      over 2 years and multiple locations using progeny of a full sib mapping
      population '549 x 372'. Dollar spot resistance seems to be inherited
      quantitatively and broad sense heritability for resistance was estimated to be
      0.88. We have detected one QTL with large effect on linkage group 7.1 with LOD
      values ranging from 3.4 to 8.6 and explaining 14-36% of the phenotypic variance.
      Several smaller effect QTL specific to rating dates, locations and years were
      also detected. The association of the tightly linked markers with the LG 7.1 QTL
      based on 106 progeny was further examined by single marker analysis on all 697
      progeny. The high significance of the QTL on LG 7.1 at a sample size of 697 (P <
      0.0001), along with its consistency across locations, years and ratings dates,
      indicated that it was stable over environments. Markers tightly linked to the QTL
      can be utilized for marker-assisted selection in future bentgrass breeding
      programs.

PMID- 16969682
TI  - [Long QT syndrome causing grand mal epilepsy: case report, pedigree, therapeutic
      options, and review of the literature].
AB  - A 24-year-old female with a history of epileptic seizures was admitted after
      prolonged cardiac resuscitation. The clinical course together with additional
      examinations led to the diagnosis of severe hypoxic cerebral damage, with poor
      prognosis for neurological outcome. In her initial ECG, as in the ECGs of several
      family members, QT prolongation was diagnosed. Meticulous history taking and
      ensuing genetic analysis led to the diagnosis of familial long QT syndrome (LQTS)
      with a mutation in the LQT-2 gene (HERG). In retrospect, the previous seizure
      episodes have to be considered cardiac syncopes. Two family members had
      previously died suddenly, and ECG and genetic analysis revealed that a total of
      eight family members were affected. These relatives were prophylactically treated
      with beta blockers or supplied with automated implantable cardioverter
      defibrillating devices. The literature concerning LQTS, diagnosis and prognosis
      of cerebral hypoxic damage, and differentiation between seizures and cardiac
      syncopes is discussed.

PMID- 16969684
TI  - Frameshift mutation in GJA12 leading to nystagmus, spastic ataxia and CNS dys
      /demyelination.
AB  - Mutations in GJA12 have been shown to cause Pelizaeus-Merzbacher-like disease
      (PMLD). We present two additional patients from one family carrying a homozygous
      frameshift mutation in GJA12. Both presented initially with nystagmus. The older
      girl developed ataxia first, then progressive spastic ataxia. The younger boy
      suffered from severe sensory neuropathy. Magnetic resonance imaging (MRI) of both
      children showed progressive demyelination in addition to dysmyelination, and also
      characteristic brainstem abnormalities. In children with nystagmus, ataxia and
      dysmyelination, mutation analysis of GJA12 should be considered early, especially
      if inheritance is autosomal recessive.

PMID- 16969685
TI  - Nuclear medicine, a paradigm of health and disease from 1985 to 2006?

PMID- 16969683
TI  - Differential involvement of the endocannabinoid system in short- and long-term
      expression of incentive learning supported by nicotine in rats.
AB  - RATIONALE: We previously reported that the CB1 cannabinoid receptor antagonist,
      rimonabant, impaired the acquisition and the short-term (24 h), but not long-term
      (3 weeks), expression of conditioned place preference (CPP) induced by nicotine
      in rats. OBJECTIVE: To assess the time interval of efficacy of a single pretest
      injection of rimonabant to abolish nicotine-CPP, and the effects of chronic CB1
      receptor blockade on long-term expression of nicotine-CPP. MATERIALS AND METHODS:
      Wistar rats were conditioned to nicotine (0.06 mg/kg, subcutaneous) using an
      unbiased one-compartment procedure. Two test sessions were conducted 24 h
      (without injection) and 1, 2, or 3 weeks later. Rimonabant (3 mg/kg,
      intraperitoneal) or vehicle was administered daily between the two test sessions.
      In addition, the CB1-stimulated [(35)S]GTP-gamma-S binding was assessed in rats
      from the 3-week experiment. RESULTS: The capacity of a single injection of
      rimonabant (3 mg/kg, 30 min pretest) to block the expression of nicotine-CPP
      disappeared within 1 week after conditioning. Daily administrations of rimonabant
      for 6, 13, or 20 days post-acquisition did not impair nicotine-CPP but allowed an
      additional pretest injection of rimonabant to retain its capacity to abolish long
      term expression of nicotine-CPP. The CB1 receptor-mediated G-protein signaling
      was not altered in various brain areas of rats given rimonabant for 3 weeks.
      CONCLUSIONS: The endocannabinoid system is essential to the expression of
      nicotine-CPP during less than 1 week after conditioning but not later. However,
      endocannabinoid-dependent mechanisms are critically involved in the development
      of the neuroadaptive changes responsible for the shift from CB1-dependent to CB1
      independent expression of nicotine incentive learning.

PMID- 16969686
TI  - Genetic polymorphism of beta-lactoglobulin gene in native Turkish sheep breeds.
AB  - The genetic polymorphism of the beta-lactoglobulin gene was investigated in three
      native Turkish sheep breeds. The study was carried out on 108 sheep (29 Kivircik,
      38 Gokceada, and 41 Sakiz) by means of PCR-RFLP methods. Two genetic variants (A
      and B) and three genotypes (AA, AB, and BB) of beta-lactoglobulin have been
      identified. The gene frequencies of beta-LG A and B were 0.7759 and 0.2241 in
      Kivircik, 0.7632 and 0.2368 in Gokceada, and 0.9756 and 0.0244 in Sakiz breeds,
      respectively. The populations were in Hardy-Weinberg equilibrium in all samples
      from the three breeds.

PMID- 16969688
TI  - Reversal of an aluminium induced alteration in redox status in different regions
      of rat brain by administration of centrophenoxine.
AB  - Aluminium is one of the most studied neurotoxin, and its effects on nervous
      system are both structural and functional, involving various regions of brain.
      Aluminium toxicity is known to have multiple mechanisms of action in the central
      nervous system. Affinity of aluminium for thiol substrates is considered a
      possible molecular mechanism involved in aluminium neurotoxicity. The reduced
      glutathione (GSH) is especially important for cellular defence against aluminium
      toxicity. This study pertains to the modulatory action of centrophenoxine on GSH
      status in aluminium exposed different brain regions of the female rats. Aluminium
      was administered orally at a dose of 40 mg/Kg x b x wt x /day for a period of
      eight weeks whereas, centrophenoxine was administered intraperitoneally at a dose
      of 100 mg/Kg x b x wt x /day for a period of six weeks. The study was carried out
      in different regions of brain namely cerebrum, cerebellum, medulla oblongata and
      hypothalamus. Animals exposed to aluminum, registered a significant decrease in
      the levels of reduced glutathione, and oxidized glutathione as well as in the
      activity of glutathione reductase in all the different regions studied when
      compared to normal control animals. Post-treatment with centrophenoxine, showed a
      significant improvement in the thiol levels in different regions. Centrophenoxine
      when administered alone also had a profound effect on the levels of reduced
      glutathione as well as on the activity of glutathione reductase. From the present
      results, it can be stated that centrophenoxine administration, as a thiol
      antioxidant, arrests the aluminium induced cellular damage by improving the thiol
      status in brain regions.

PMID- 16969687
TI  - Induction of apoptosis by quercetin: different response of human chronic myeloid
      (K562) and acute lymphoblastic (HSB-2) leukemia cells.
AB  - This work shows that 25 microM quercetin caused a marked inhibition of K562 cells
      growth together with a mild cytotoxicity, while HSB-2 cells were practically
      unaffected. Moreover, quercetin induced caspase-3 and cytochrome c-dependent
      apoptosis almost exclusively in the former cell line. Exposure of K562 cells to
      quercetin caused also a significant increase of cells in G(2)/M phase that
      reached the maximum peak at 24 h (4-fold with respect to the basal value). The
      major sensitivity exhibited by K562 cells was only in part imputable to their
      higher glutathione content, as compared to HSB-2 cells, thus confirming previous
      reports describing the formation of intracellular quercetin-thiol toxic adducts
      in cells exposed to the flavonoid. In fact, after induction of intracellular
      glutathione increase we detected in both cell lines a significant rise of
      apoptotic cells, again more marked in K562 cells. By contrast, glutathione
      depleted cells, failed to show a decrease of apoptosis in both cell lines, thus
      contradicting our previous findings and literature data. Since the yet unresolved
      question about the anti-oxidant or the pro-oxidant capacity of quercetin, we
      investigated which of these two properties worked in our experimental model.
      Interestingly, not only quercetin did not produce reactive oxygen species but
      also prevented their formation, as observed in cells exposed to the oxidizing
      agent ter-butylhydroperoxide, acting as an efficient oxygen radicals scavenger.
      This result indicates that quercetin exhibited, in these cell lines, anti-oxidant
      more than pro-oxidant ability.

PMID- 16969689
TI  - Evidence for centrophenoxine as a protective drug in aluminium induced behavioral
      and biochemical alteration in rat brain.
AB  - Potential use of various nootropic drugs have been a burning area of research on
      account of various physical and chemical insult in brain under different
      toxicological conditions. One of the nootropic drug centrophenoxine, also known
      as an anti-aging drug has been exploited in the present experiment under
      aluminium toxic conditions. Aluminium was administered by oral gavage at a dose
      level of 100 mg/Kg x b x wt/day for a period of six weeks. To elucidate the
      region specific response, study was carried out in two different regions of brain
      namely cerebrum and cerebellum. Following aluminium exposure, a significant
      decrease in the activities of enzymes namely Hexokinase, Lactate dehydrogenase,
      Succinate dehydrogenase, Mg(2+) dependent ATPase was observed in both the
      regions. Moreover, the activity of acetylcholinesterase was also reported to be
      significantly decreased. Post-treatment with centrophenoxine was able to restore
      the altered enzyme activities and the effect was observed in both the regions of
      brain although the activity of lactate dehydrogenase and acetylcholinesterase did
      not register significant increase in the cerebellum region. Further,
      centrophenoxine was able to improve the altered short-term memory and cognitive
      performance resulted from aluminium exposure. From the present study, it can be
      concluded that centrophenoxine has a potential and can be exploited in other
      toxicological conditions also.

PMID- 16969690
TI  - Stoichiometrically different inclusion complexes of 2-aminofluorene and 2-amino-9
      hydroxyfluorene in beta-cyclodextrin: a spectrofluorimetric study.
AB  - Beta-cyclodextrin (beta-CDx) forms inclusion complexes with 2-aminofluorene (2AF)
      and 2-amino-9-hydroxyfluorene (2AHF) in different stoichiometries (Guest-host
      ratio 1:1 and 1:2 respectively) which is discussed on the basis of study by
      absorption and fluorescence spectroscopy. The ground and the excited state
      acidity constants for the neutral-monocation equilibrium of the two fluorophores
      in aqueous beta-CDx medium are determined by spectrophotometric and fluorimetric
      titration methods respectively. The dual fluorescence observed for 2AHF
      monocation in aqueous solution is due to the formation of monocation-water
      exciplex. This monocation-water exciplex formation is hindered in beta-CDx
      solution by the inclusion complexation. Based on the results obtained, the
      structures of the inclusion complexes are proposed.

PMID- 16969691
TI  - Evaluation of a respiratory muscle biofeedback procedure-effects on heart rate
      and dyspnea.
AB  - Patients with respiratory diseases or anxiety frequently complain about dyspnea,
      which may be partly related to chronic tension of respiratory muscles and/or
      dynamic hyperinflation. In two experiments we tested a biofeedback technique that
      recorded electromyographic (EMG) activity from a bipolar surface electrode
      placement over the right external intercostal muscles with visual signal
      feedback. Healthy participants were tested in their ability to alter the signal.
      Heart rate was measured continuously throughout training trials. In the second
      experiment, dyspnea was rated on a modified Borg scale after each trial.
      Participants were able to increase their EMG activity considerably while heart
      rate and dyspnea increased substantially. Changes in EMG activity were achieved
      mostly by manipulating accessory muscle tension and/or altering breathing
      pattern. Thus, the technique is capable of altering respiratory muscle tension
      and associated dyspnea. Further studies may test the procedure as a relaxation
      technique in patients with respiratory disease or anxiety.

PMID- 16969692
TI  - Controlling protein compartmentalization to overcome disease.
AB  - Over the past decade, considerable progress has been made to improve our
      understanding of the intracellular transport of proteins. Mechanisms of nuclear
      import and export involving classical receptors have been studied. Signal
      sequences required for directing a protein molecule to a specific cellular
      compartment have been defined. Knowledge of subcellular trafficking of proteins
      has also increased our understanding of diseases caused due to mislocalization of
      proteins. A specific protein on deviating from its native cellular compartment
      may result in disease due to loss of its normal functioning and aberrant activity
      in the "wrong" compartment. Mislocalization of proteins results in diseases that
      range from metabolic disorders to cancer. In this review we discuss some of the
      diseases caused due to mislocalization. We further focus on application of
      nucleocytoplasmic transport to drug delivery. Various rationales to treat
      diseases by exploiting intracellular transport machinery have been proposed.
      Although the pathways for intracellular movement of proteins have been defined,
      these have not been adequately utilized for management of diseases involving
      mislocalized proteins. This review stresses the need for designing drug delivery
      systems utilizing these mechanisms as this area is least exploited but offers
      great potential.

PMID- 16969693
TI  - Disruption of epithelial tight junctions by yeast enhances the paracellular
      delivery of a model protein.
AB  - PURPOSE: The aim of this study was to investigate the effect of heat-killed yeast
      cells on the integrity of epithelial tight junctions in vitro. METHODS: Changes
      in barrier potential of Caco-2 cell monolayers were assessed by transepithelial
      electrical resistance (TEER) measurements and by an increasing permeability to a
      marker protein, horse-radish peroxidase (HRP). Visualisation of tight junction
      disruption was carried out directly through electron microscopy and indirectly
      through fluorescence confocal microscopy and immunoblotting of the tight junction
      associated proteins zonula occludens ZO-1, occludin and actin. RESULTS: Yeast
      cells opened tight junctions in a reversible dose- and time-dependent manner, as
      shown by a decrease in TEER and an increase in HRP permeability. These changes to
      barrier potential were shown not to be due to cytotoxic effects but due to
      modulation of the tight junctions. ZO-1, actin and occludin proteins were
      demonstrated to be involved in yeast-induced tight junction opening through the
      use of confocal microscopy and western blotting. Electron microscopy confirmed a
      direct opening of tight junctions after application of yeast. CONCLUSION: Yeast
      modulated epithelial tight junctions in a reversible manner by contraction of the
      actin cytoskeleton and shift of ZO-1 and occludin tight junction proteins from
      the membrane to cytoskeletal areas of the cell.

PMID- 16969694
TI  - Modeling cardiac uptake and negative inotropic response of verapamil in rat
      heart: effect of amiodarone.
AB  - PURPOSE: To determine the effect of the P-glycoprotein (Pgp) modulator amiodarone
      on the pharmacokinetics and pharmacodynamics (PK/PD) of Pgp substrate verapamil
      in the perfused rat heart. METHODS: In Langendorff-perfused rat hearts, the
      outflow concentration-time curve and inotropic response data were measured after
      a 1.5 nmol dose of [3H]-verapamil (infused within 1 min) in the absence and
      presence of the amiodarone (1 microM) in perfusate, as well as using a double
      dosing regimen (0.75 nmol in a 10 min interval). These data were analyzed by a
      PK/PD model. RESULTS: Amiodarone failed to influence the rapid uptake and
      equilibrium partitioning of verapamil into the heart. The time course of the
      negative inotropic effect of verapamil, including the 'rebound' above the
      original baseline after the infusion of verapamil was stopped, could be described
      by a PK/PD tolerance model. Tolerance development (mean delay time, 12 min) led
      to a reduction in predicted steady-state effect (16%). The EC50 and Emax values
      as estimated in single dose experiments were 16.4+/-4.1 nM and 50.5+/-18.9 mmHg,
      respectively. CONCLUSIONS: The result does not support the hypothesis that Pgp
      inhibition by amiodarone increases cardiac uptake of the Pgp substrate verapamil.

PMID- 16969695
TI  - Characterization of hepatobiliary transport systems of a novel
      alpha4beta1/alpha4beta7 dual antagonist, TR-14035.
AB  - PURPOSE: Our previous pharmacokinetic studies have demonstrated that TR-14035, a
      novel dual antagonist for alpha4beta1/alpha4beta7 integrin, selectively and
      strongly accumulated in the liver and was mainly excreted in bile as an unchanged
      drug. In the present study, we investigated the hepatobiliary transport system in
      detail. MATERIALS AND METHODS: Uptake by hepatocytes and organic anion
      transporting polypeptide (OATP)-expressing Xenopus laevis oocytes or Flp-In-293
      cells was performed in vitro. Biliary excretion was investigated in mdr1a/b
      knockout mice, Bcrp-knockout mice and Mrp2-defective Eisai hyperbilirubinemic
      rats (EHBRs). RESULTS: TR-14035 was taken up by rat and human hepatocytes by an
      apparently single saturable mechanism with K(m) of 6.7 and 2.1 microM,
      respectively, and taurocholate and digoxin reduced this uptake. OATP1B1/OATP-C
      and OATP1B3/OATP8 expressed in oocytes mediated the TR-14035 uptake with K(m) of
      7.5 and 5.3 microM, respectively. OATP1B1*15, a genetic variant of OATP1B1,
      exhibited a decreased transport of TR-14035 compared with OATP1B1*1a. Biliary
      excretion and total body clearance of unchanged TR-14035 in EHBRs were
      significantly lower than those in normal rats, while there was no difference in
      the clearances between wild and mdr1a/b- or Bcrp-knockout mice. CONCLUSION: These
      results indicate that OATP1B1 and OATP1B3 are at least partly responsible for the
      accumulation of TR-14035 into hepatocytes, and Mrp2 principally mediates the
      biliary excretion of TR-14035. Furthermore, genetic polymorphisms of OATP1B1 may
      cause an interindividual variability in the pharmacokinetics of TR-14035.

PMID- 16969696
TI  - Intracellular delivery of saquinavir in biodegradable polymeric nanoparticles for
      HIV/AIDS.
AB  - PURPOSE: This study aims at developing poly(ethylene oxide)-modified poly(epsilon
      caprolactone) (PEO-PCL) nanoparticulate system as an intracellular delivery
      vehicle for saquinavir, an anti-HIV protease inhibitor. MATERIALS AND METHODS:
      Saquinavir-loaded PEO-PCL nanoparticles were prepared by a solvent displacement
      process. The formed nanoparticles were characterized for size, surface charge,
      and surface presence of PEO chains. Cellular uptake and distribution of the
      nanoparticle was examined in THP-1 human monocyte/macrophage (Mo/Mac) cell line.
      Intracellular saquinavir concentrations were measured as a function of dose and
      duration of incubation. RESULTS: The PEO-PCL nanoparticles had a smooth surface
      and spherical shape and showed a relatively uniform size distribution with a mean
      particle diameter of approximately 200 nm. The surface presence of PEO chains was
      confirmed by an increase in the -C-O-(ether) signature of the C1s spectra in
      electron spectroscopy for chemical analysis. Rapid cellular uptake of rhodamine
      123 encapsulated PEO-PCL nanoparticles was observed in THP-1 cells. Intracellular
      saquinavir concentrations when administered in the nanoparticle formulation were
      significantly higher than from aqueous solution. CONCLUSIONS: This study shows
      that PEO-PCL nanoparticles provide a versatile platform for encapsulation of
      saquinavir and subsequent intracellular delivery in Mo/Mac cells.

PMID- 16969697
TI  - Pharmacogenomics of phenolic antioxidant butylated hydroxyanisole (BHA) in the
      small intestine and liver of Nrf2 knockout and C57BL/6J mice.
AB  - PURPOSE: The objective of this study was to investigate the pharmacogenomics and
      the spatial regulation of global gene expression profiles elicited by cancer
      chemopreventive agent butylated hydroxyanisole (BHA) in mouse small intestine and
      liver as well as to identify BHA-modulated nuclear factor-E2-related factor 2
      (Nrf2)-dependent genes. METHODS: C57BL/6J (+/+; wildtype) and C57BL/6J/Nrf2(-/-;
      knockout) mice were administered a single 200 mg/kg oral dose of BHA or only
      vehicle. Both small intestine and liver were collected at 3 h after treatment and
      total RNA was extracted. Gene expression profiles were analyzed using 45,000
      Affymetrix mouse genome 430 2.0 array and GeneSpring 7.2 software. Microarray
      results were validated by quantitative real-time reverse transcription-PCR
      analyses. RESULTS: Clusters of genes that were either induced or suppressed more
      than two fold by BHA treatment compared with vehicle in C57BL/6J/Nrf2(-/-;
      knockout) and C57BL/6J Nrf2 (+/+; wildtype) mice genotypes were identified.
      Amongst these, in small intestine and liver, 1,490 and 493 genes respectively
      were identified as Nrf2-dependent and upregulated, and 1,090 and 824 genes
      respectively as Nrf2-dependent and downregulated. Based on their biological
      functions, these genes can be categorized into ubiquitination/proteolysis,
      apoptosis/cell cycle, electron transport, detoxification, cell
      growth/differentiation, transcription factors/interacting partners, kinases and
      phosphatases, transport, biosynthesis/metabolism, RNA/protein processing and
      nuclear assembly, and DNA replication genes. Phase II detoxification/antioxidant
      genes as well as novel molecular target genes, including putative interacting
      partners of Nrf2 such as nuclear corepressors and coactivators, were also
      identified as Nrf2-dependent genes. CONCLUSIONS: The identification of BHA
      regulated and Nrf2-dependent genes not only provides potential novel insights
      into the gestalt biological effects of BHA on the pharmacogenomics and spatial
      regulation of global gene expression profiles in cancer chemoprevention, but also
      points to the pivotal role of Nrf2 in these biological processes.

PMID- 16969698
TI  - Chemical and thermal stability of insulin: effects of zinc and ligand binding to
      the insulin zinc-hexamer.
AB  - PURPOSE: To study the correlation between the thermal and chemical stability of
      insulin formulations with various insulin hexamer ligands. MATERIALS AND METHODS:
      The thermal stability was investigated using differential scanning calorimetry
      (DSC) and near-UV circular dichroism (NUV-CD). The formation of chemical
      degradation products was studied with reversed-phase and size-exclusion
      chromatography and mass spectrometry. RESULTS: An excellent correlation between
      the thermal stabilization by ligand binding and the deamidation of Asn(B3) was
      observed. The correlation between thermal stability and the formation of covalent
      dimer and other insulin related products was less clear. Zinc was found to
      specifically increase the deamidation and covalent dimer formation rate when the
      insulin hexamer was not further stabilized by phenolic ligand. Thiocyanate alone
      had no effect on the thermal stability of the insulin zinc-hexamer but
      significantly improved the chemical stability at 37 degrees C. At low
      temperatures thiocyanate induced a conformational change in the insulin hexamer.
      NUV-CD thermal scans revealed that this effect decreased with temperature; when
      the thermal denaturation temperature was reached, the effect was eliminated.
      CONCLUSIONS: Thermal stability can be used to predict the rate of Asn(B3)
      deamidation in human insulin. Chemical degradation processes that do not rely on
      the structural stability of the protein do not necessarily correlate to the
      thermal stability.

PMID- 16969699
TI  - Data analysis of kinetic modelling used in drug stability studies: isothermal
      versus nonisothermal assays.
AB  - PURPOSE: Kinetic modelling was applied to predict the stability of
      cholecystokinin fragment CCK-4 in aqueous solution, which was analyzed by
      isothermal and nonisothermal methods using a validated stability indicating HPLC
      method. METHODS: The isothermal studies were performed in the temperature range
      40 to 80 degrees C at pH 12 and ionic strength 0.01 M as constants, whereas
      nonisothermal stability studies were performed using a linear increasing
      temperature program, heating rate 0.25 degrees C/h and a temperature interval 40
      82 degrees C. The isothermal studies require two-step linear regression to
      estimate the parameters, resulting in a well-defined confidence interval.
      Nonisothermal kinetic studies require nonlinear or linear regression by previous
      transformation of data to estimate the parameters. In this case, the two most
      popular approaches, derivative and integral, were used and compared. RESULTS:
      Under isothermal conditions, an apparent first-order degradation process was
      observed at all temperatures. The linear Arrhenius plot suggested that the CCK-4
      degradation mechanism was the same within the studied temperature range, with
      quite large uncertainties due to the small number of degrees of freedom based
      only on the scatter in the plot, and giving an estimated shelf life at 25 degrees
      C of 35.2 days. The derivative approach yields high variability in the Arrhenius
      parameters, since they are dependent on the number of polynomial terms chosen, so
      several statistical criteria were applied to select the best model. The integral
      approach allows activation parameters to be calculated directly from experimental
      data, and provides results in good agreement with those of the traditional
      method, but have the advantage that the uncertainty in the final result directly
      reflects the goodness of fit of the experimental data to the chosen kinetic
      model. The application of the bootstrap technique to estimating confidence limits
      for the Arrhenius parameters and shelf life is also illustrated, and shows there
      is no difference between the asymptotic and bootstrap confidence intervals.
      CONCLUSIONS: Nonisothermal studies give us fast and valuable information about
      drug stability, although their potential for predicting isothermal behaviour is
      conditioned by the data analysis method applied.

PMID- 16969700
TI  - Molecular interaction among probucol/PVP/SDS multicomponent system investigated
      by solid-state NMR.
AB  - PURPOSE: Effects of polyvinylpyrrolidone (PVP) molecular weight on the solid
      state intermolecular interactions among probucol/PVP/sodium dodecyl sulfate (SDS)
      ternary ground mixtures (GM) and the formation of nanoparticles were investigated
      by solid-state NMR spectroscopy. MATERIALS AND METHODS: Ternary GMs of probucol
      were prepared with PVP (K12, K17, K30 or K90) and SDS at a weight ratio of 1:3:1
      and were ground for 15, 30 and 60 min. Solid-state interactions were evaluated
      using powder X-ray diffraction (PXRD) and solid-state cross polarization/magic
      angle spinning (CP/MAS) (13)C NMR spectroscopy. A high resolution scanning
      electron microscopy (SEM) was employed to observe nanoparticles of probucol in
      the GM. RESULTS: The solid-state (13)C CP/MAS NMR results indicate that the low
      molecular weight PVP interacts with probucol and SDS more strongly than the high
      molecular weight PVP in the ternary GM. This finding was consistent with the
      result that smaller drug nanoparticles were obtained using low molecular weight
      of PVP. SEM images of probucol/PVP K12/SDS confirmed the presence of
      nanoparticles (15-25 nm) in the GM. CONCLUSIONS: Grinding-induced solid-state
      interactions among drug, PVP and SDS could be detected using solid state (13)C
      NMR. The interactions in both probucol-PVP and PVP-SDS should occur
      simultaneously to generate nanometer-sized particles of probucol.

PMID- 16969701
TI  - Polymorph farming of acetaminophen and sulfathiazole on a chip.
AB  - PURPOSE: The aim of this paper is to understand at a given temperature (1) the
      role of template films, the droplet volume of a saturated sulfathiazole aqueous
      solution and the solvent on polymorph screening of sulfathiazole on a silicon
      wafer, and (2) the effect of template films on the acetaminophen crystal face at
      the template-crystal interface. MATERIALS AND METHODS: Template Effect: Spun cast
      template films of non-annealed chitosan and annealed chitosan at 140 degrees C on
      silicon wafers were prepared. A 0.01-cm(3) saturated sulfathiazole aqueous
      solution droplets were deposited on both kinds of chitosan film. Sulfathiazole
      crystals were produced on those films by evaporation at 25 degrees C. Volume
      Effect: Different droplet volumes of a saturated sulfathiazole aqueous solution
      ranging from 0.01 to 0.14 to 2.7 cm(3) were deposited on non-annealed chitosan
      films. Sulfathiazole crystals were generated on those films by evaporation at 25
      degrees C. Solvent Effect: 0.01 cm(3) saturated sulfathiazole methanol solution
      droplets were deposited on non-annealed chitosan films and sulfathiazole crystals
      were formed on those films by evaporation at 25 degrees C. The formation pathways
      of different sulfathiazole crystal polymorphs of the above mentioned effects were
      analyzed and verified by systematic studies. Template-crystal Interfacial Study:
      Millimeter-sized acetaminophen crystals were successfully grown on non-annealed
      chlorosulfonated poly(ethylene) (PE-Chl) and chitosan template films by cooling
      the saturated acetaminophen aqueous solution from 50 to 25 degrees C in which
      those template films were immersed. The bonding energies for specific carbons
      collected by electron spectroscopy for chemical analysis (ESCA) at the
      acetaminophen crystal surface, together with the molecular interactions between
      acetaminophen and PE-Chl and between acetaminophen and chitosan in separately
      prepared solid dispersion film samples detected by Fourier transformed infrared
      (FTIR) spectroscopy, proved to be useful for identifying the crystal face of
      acetaminophen essential for its specific intermolecular interactions at the
      template-crystal interface. RESULTS: Thermodynamically metastable sulfathiazole
      Form I crystals were reproducibly obtained on the non-annealed chitosan films
      whereas the stable sulfathiazole Form III crystals were repeatedly formed on the
      annealed chitosan films. Droplet volumes and solvents were also found responsible
      for the polymorphic outcome of sulfathiazole in the kinetically driven area of
      two overlapping metastable zones from two competing polymorphs of Form I and Form
      III. Thermodynamically stable sulfathiazole Form III crystals were formed on the
      non-annealed chitosan films instead when the droplet volumes of a saturated
      sulfathiazole aqueous solution were increased from 0.01 to 0.14 cm(3) and 2.7
      cm(3). When the solvent was changed from water to methanol, the thermodynamically
      stable sulfathiazole Form III crystals were again observed on the non-annealed
      chitosan films even from the 0.01 cm(3) saturated sulfathiazole methanol solution
      droplets. CONCLUSIONS: Template surfaces were thought to provide specific
      functional groups to either change the energy barrier for the nuclei formation of
      the thermodynamically metastable Form I or alter the droplet contact angle and
      the droplet surface area which was related to the droplet evaporation time. The
      evaporation time determines the amount of time available for the polymorphic
      transformation from Form I to Form III. Apparently, droplet volumes could also
      determine the amount of time needed to reach supersaturation and the amount of
      time available for a polymorphic transformation from Form I to Form III. In
      addition, the molecular conformation and viscosity of solvents such as methanol
      might alter the original nucleation kinetics in water and lead to a more rapid
      polymorphic transformation from Form I to Form III. Template films of PE-Chl and
      chitosan were found to be critical for determining the face of a millimeter-sized
      acetaminophen crystal at the template-crystal interface. The idea of performing
      polymorph screening on the template film deposited on a chip has opened up a new
      doorway to examine the roles of: (1) various kinds of drug carrier in the form of
      a template film, (2) the droplet volume of a saturated solution, and (3) the type
      of solvent used, in polymorphic control. Growing millimeter-sized crystals
      directly on the chip of template has also provided a convenient technology
      enabling platform for examining the crystal-template interface by solid-state
      characterization techniques such as ESCA.

PMID- 16969702
TI  - From neurotic guilt to existential guilt as grief: the road to interiority,
      agency, and compassion through mourning. Part I.
AB  - This study proposes through a case illustration that psychoanalytic patients who
      can process both aggression and loss through a mourning process are able to free
      themselves from pathological self attack when the object relations work of
      attachment, psychic holding, and separation transpires. In the case of Helen
      discussed here, transformation through a "developmental mourning process" results
      in the evolution of powerful psychological capacities for interiority, self
      agency, and interpersonal compassion. This developmental mourning process is
      endowed with the assimilation and psychic fantasy symbolization of aggression.

PMID- 16969703
TI  - Male-produced pheromone of the green lacewing, Chrysopa nigricornis.
AB  - Gas chromatographic-electroantennographic detection (GC-EAD) analysis showed that
      male antennae of the green lacewing, Chrysopa nigricornis Burmeister, the most
      common lacewing species in the U.S. Pacific Northwest, consistently responded to
      two compounds in thoracic extracts of conspecific males: 1-tridecene and
      (1R,2S,5R,8R)-iridodial. These compounds were not detected in extracts of the
      abdominal cuticle, and no other antennally active compounds were found in the
      abdominal samples. In field-trapping experiments, traps baited with iridodial
      significantly attracted large numbers of C. nigricornis males (both western and
      eastern forms) during summer and early fall, plus a few individuals of
      conspecific females only in early fall. Iridodial also attracted males of the
      goldeneyed lacewing, C. oculata Say, and, to a lesser extent, C. coloradensis
      Banks males. Methyl salicylate (MS), reported as an attractant for both sexes of
      C. nigricornis and C. oculata, was inactive by itself at the concentration tested
      in our study, but in a few instances slightly enhanced the responses of Chrysopa
      spp. to iridodial. However, MS alone and its binary blend with iridodial seemed
      to attract the hoverfly, Metasyrphus americanus (Weidemann). 2-Phenylethanol, a
      reported attractant for another lacewing, Chrysoperla plorabunda (Fitch) [=carnea
      (Say)], did not capture any lacewings. Our assays indicated that the lacewing
      pheromone, iridodial, loaded onto either rubber septa or as a binary blend with
      MS in polyethylene bags could last at least 5 wk in the field during the summer
      season. Based on this study, a new attractant system for green lacewings is being
      developed for both domestic and international markets.

PMID- 16969704
TI  - Do predictors of gambling involvement differ across male and female adolescents?
AB  - We examined gender-specific factors, which might be related to adolescent
      gambling behavior, using a comprehensive set of predictors from neighborhood,
      school, family, peer, and intrapersonal domains. Discriminate function analyses
      revealed a unique pattern of results for each gender. The noteworthy predictors
      for males were similar to what is found to be predictors of other risk behaviors,
      suggesting that there may be a similar etiology to gambling participation as
      found with other risk behaviors. Compared to males, the model for females
      suggests that parents and peers may have a greater influence on engagement in
      gambling behavior. Participation in unstructured activities, and risk
      attitudes/perceptions were the only consistent noteworthy predictors across both
      males and females. Implications are discussed.

PMID- 16969705
TI  - "That's not his only problem..." clinical teamwork in a psychiatric emergency
      room.
AB  - This article is a qualitative study of the social organization of clinical work
      in a psychiatric emergency room. The research involved observation of emergency
      room practices and interviews with the clinical staff members. Due to
      responsibility of ensuring confidentiality, audio taping was not possible.
      Observations and interviews were recorded by hand, and thus, except in brief
      instances, I describe talk rather than reproduce it verbatim. Psychiatry, I
      argue, should not be explored as a singular profession but as the team practice
      of a team of occupational groups. These groups are often seen as subordinate to
      psychiatric physicians, but as this paper will demonstrate these groups are often
      able to call upon their specific claims to expert knowledge to assume clinical
      authority over a patient's diagnosis and treatment. The successful pursuit of
      such a claim puts these clinical occupational groups in a position to challenge
      psychiatrists over crucial hospital resources such as beds. These groups' claim
      to authority emerges from two sources. The first is their specific histories and
      their clinical knowledge systems that initially developed independently of
      cosmopolitan medicine. The second is the political economic environment of urban
      hospital psychiatric departments which largely treat patients with opaque
      symptoms of unclear origin that defy easy psychiatric classification.

PMID- 16969707
TI  - Rebeccamycin analog for refractory breast cancer: a randomized phase II trial of
      dosing schedules.
AB  - Rebeccamycin analog (NSC 655649) is a synthetic antibiotic cytotoxic agent
      thought to inhibit topoisomerase function. We sought to determine the response
      rate to rebeccamycin analog among patients with refractory advanced breast cancer
      using two different treatment schedules. Eligible patients had measurable
      disease, central venous access, and one or two prior chemotherapy regimens for
      advanced cancer, or recurrence within 12 months of adjuvant chemotherapy.
      Patients were randomized to rebeccamycin analog on one of two treatment
      schedules: arm 1, 500 mg/m2 IV bolus every 21 days; arm 2, 140 mg/m2 IV bolus
      daily x 5 days, every 21 days. The primary study endpoint was response rate; a
      two stage accrual design evaluated each schedule separately. Forty-two women
      entered the trial, 21 on each arm. Prior chemotherapy regimens for metastatic
      breast cancer were: 0, n=4; 1, n=21; 2, n=17. Prior treatments (including
      adjuvant therapy) anthracyclines: 88%, taxanes 67%, 5FU-based therapy, 50%. There
      were 5 partial responses (overall response rate 12%), two in arm 1 and 3 in arm
      2, all in patients with prior anthracycline-based adjuvant chemotherapy. Median
      time to progression was 2.1 months (range 1-14+ months). An additional 9 patients
      had stable disease as best response. Grade 3 or 4 toxicity rates were: anemia 5%,
      neutropenia 33%, thrombocytopenia 12%, RBC transfusion 14%, nausea/vomiting 10%.
      Toxicity profiles were similar between the treatment arms. Rebeccamycin analog is
      reasonably well tolerated on two different treatment schedules for advanced
      breast cancer, with modest clinical activity in this heavily pretreated
      population.

PMID- 16969706
TI  - Phase I safety, pharmacokinetic and pharmacodynamic studies of 2-methoxyestradiol
      alone or in combination with docetaxel in patients with locally recurrent or
      metastatic breast cancer.
AB  - PURPOSE: We report the first phase I trials of 2-methoxyestradiol (2ME2, Panzem
      Capsules, EntreMed, Rockville, MD), alone and in combination with docetaxel, in
      patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: In Trial 001,
      2ME2 monotherapy was administered orally once (200-1000 mg/d, cohorts 1-5) or
      twice daily (200-800 mg/q12h, cohorts 6-9) for 28 days followed by a 14-day
      observation period, continuously thereafter. In Trial 002, docetaxel 35 mg/m(2)
      was administered weekly for four of six weeks for a maximum six cycles; 2ME2 (200
      1000 mg/d) was given orally once daily for 28 days followed by a 13-day
      observation period in cycle one, continuously thereafter. In both trials,
      responding or stable patients continued 2ME2 until progression. RESULTS: Trial
      001 enrolled 31 patients; there were no objective responses. Trial 002 enrolled
      15 patients; ORR was 20% including one CR. There were no Grade IV toxicities; MTD
      was not reached in either study. When combined with docetaxel, three patients had
      significant transaminase elevations that returned to normal with continued
      treatment (in two of three patients). There was significant inter-patient
      variability and extensive metabolism to 2-methoxyestrone (2ME1). Steady-state AUC
      and trough concentrations of 2ME2 increased linearly up to 400-600 mg/d; doses
      above 400-600 mg/d did not increase 2ME2 levels. The target trough concentration
      (3-25 ng/mL) was not attained. Combined administration did not alter docetaxel or
      2ME2 pharmacokinetics. CONCLUSION: 2ME2, alone or in combination with docetaxel,
      was well tolerated in patients with MBC but systemic exposure remained below the
      expected therapeutic range.

PMID- 16969708
TI  - Assessing the predictive accuracy of hMLH1 and hMSH2 mutation probability models.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is characterized by a
      susceptibility to colorectal and extra-colonic cancers. Several guidelines exist
      for the identification of families suspected of having HNPCC, however these
      guidelines lack adequate sensitivity and specificity. In an attempt to improve
      accuracy for the detection of individuals with HNPCC, the Wijnen pre-test
      probability model (1998) and Myriad Genetics Laboratory prevalence table (2004)
      were developed. Here we evaluate the Wijnen model and Myriad table at predicting
      the presence of a mutation in individuals undergoing genetic testing for HNPCC.
      Forty-nine patients who had undergone genetic testing for germline mutations in
      hMLH1 and/or hMSH2 were part of our analysis. Our results revealed that the
      revised Bethesda guidelines performed with the highest sensitivity for germline
      mutations (94.4%), however the specificity was low (12.9%). Using a 10.0%
      mutation probability threshold, the Wijnen model and Myriad table had
      sensitivities of 55.6 and 60.0%, respectively and specificities of 54.8 and
      23.8%, respectively. The Wijnen model and Myriad table were poor predictors of
      mutation prevalence, which is shown by the areas underneath their corresponding
      receiver operator characteristic curves (0.616 and 0.400, respectively). The
      results of this study demonsrate that neither the Wijnen model nor the Myriad
      table are sensitive or specific enough to be used as the only indication when to
      offer genetic testing for HNPCC.

PMID- 16969709
TI  - HMG-CoA reductase is regulated by salinity at the level of transcription in
      Haloferax volcanii.
AB  - The moderately halophilic archaeon Haloferax volcanii was surveyed for protein
      profile changes correlated with growth at high and low salinity. A single
      polypeptide with an approximate mass of 46 kDa was conspicuously more abundant
      during growth at high salinity. This protein was identified as HMG-CoA reductase
      (HMGR), encoded by the hmgR gene. HMGR is a key enzyme in the mevalonate pathway
      of isoprenoid biosynthesis, the sole route in haloarchaea for lipid and
      carotenoid production. Enzymatic assays confirmed that HMGR activity is more
      abundant in cells grown at high salinity. Low salt cultures of H. volcanii
      contained lower amounts of hmgR transcript compared to cells grown in high salt
      suggesting that the observed regulation occurs at the level of transcription.
      Paradoxically, both lipid and carotenoid content decreased in H. volcanii grown
      at high salinity despite the increased levels of HMGR specific activity. To our
      knowledge, this is the first report demonstrating that the expression of HMGR is
      regulated in response to non-optimal salinity in a halophilic archaeon.

PMID- 16969710
TI  - Biochemical and phylogenetic characterization of a novel terrestrial
      hyperthermophilic archaeon pertaining to the genus Pyrococcus from an Algerian
      hydrothermal hot spring.
AB  - A hyperthermophilic anaerobic archeon, strain HT3, was isolated from hydrothermal
      hot spring in Northeast Algeria. The strain is a regular coccus, highly motile,
      obligatory anaerobic, heterotrophic. It utilizes proteinaceous complex media
      (peptone, tryptone or yeast extract). Sulfur is reduced to Hydrogen sulfide and
      enhances growth. It shares with other Pyrococcus species the heterotrophic mode
      of nutrition, the hyperthermophily, the ability to utilize amino acids as sole
      carbon and nitrogen sources and the ether lipid composition. The optimal growth
      occurs at 80-85 degrees C, pH 7.5 and 1.5% NaCl. The G + C content was 43 mol%.
      Considering its morphology, physiological properties, nutritional features and
      phylogenetic analyses based on 16S rRNA gene sequencing, this strain is described
      as a new terrestrial isolate pertaining to the genus Pyrococcus.

PMID- 16969711
TI  - Zinc status, psychological and nutritional assessment in old people recruited in
      five European countries: Zincage study.
AB  - The paper shows the results on the relationship between zinc status,
      psychological dimensions (cognitive functions, mood, perceived stress) and
      nutritional aspects in European healthy old subjects recruited for ZINCAGE
      Project (supported by the European Commission in the Sixth Framework Programme).
      The old healthy subjects were recruited in Italy, Greece, Germany, France, Poland
      taking into account the different dietary habits between Northern and Southern
      European Countries and the pivotal role played by zinc for psychological
      functions. Measures of the cognitive status, mood and perceived stress level were
      obtained at baseline, using the "Mini Mental State Examination (MMSE)"; the
      "Geriatric Depression Scale (GDS - 15 items)" and the "Perceived Stress Scale
      (PSS)", respectively. Nutritional status was assessed using "Frequency Food
      Questionnaire". The sample included 853 old subjects, classified in 4 groups of
      age: 60-69-years-old (n = 359); 70-74-years-old (n = 225); 75-79-years-old (n =
      153); 80-84-years-old (n = 116). Subjects were studied on the basis of plasma
      zinc, in which zinc </=11 microM means marginal zinc deficiency. The total
      samples showed that the 82% had no cognitive decline, whereas 76% presented a low
      GDS value indicating no depression. However, all psychological variables were
      related to plasma zinc values and nutritional assessment. In particular, a
      relationship between marginal zinc deficiency and impaired psychological
      dimensions occurred in Greece than in other European countries due to low intake
      and less variety of foods rich of zinc. This phenomenon was independent by the
      age, suggesting that a correct zinc intake from a wide range of foods may be
      useful to maintain a satisfactory plasma zinc levels as well as psychological
      status in elderly with subsequent achievement of healthy ageing.

PMID- 16969712
TI  - Dietary restriction, glycolysis, hormesis and ageing.
AB  - The possibility is discussed that dietary restriction modulates ageing and onset
      of related pathologies by, in addition to upregulation of proteolysis,
      suppression of glycolysis which in turn decreases generation of methylglyoxal
      (MG), a highly toxic glycating agent which can provoke cellular senescence and
      many age-related pathologies. This proposal is supported by the observation that
      intermittent feeding can mimic dietary restriction's effects on mouse lifespan
      without any overall reduction in calorie intake. That MG-induced modification of
      the chaperone and anti-apoptotic protein (Hsp27) increases its protective
      functions suggests a possible hormetic response to transient MG production during
      transient periods of glycolysis in dietary restricted animals. It is suggested
      that in the ad libitum-fed state permanent glycolysis would suppress proteolysis
      and continuously generate MG which overwhelms the anti-MG defence systems. It is
      proposed that periods of fasting might be a more acceptable approach than
      permanent undernutrition in our attempts to slow human ageing, although timing of
      meals may prove important.

PMID- 16969713
TI  - Ningalooia psammopercae n. g., n. sp. (Digenea: Acanthocolpidae) from the Waigieu
      seaperch Psammoperca waigiensis (Cuvier) (Perciformes: Latidae) on the Ningaloo
      Reef, Western Australia.
AB  - Ningalooia psammopercae n. g., n. sp. is described from the intestine of the
      Waigieu seaperch Psammoperca waigiensis Cuvier (Perciformes: Latidae) on the
      Ningaloo Reef, Western Australia. The new genus and species are distinctive
      within the Acanthocolpidae for the combination of the absence of enlarged spines
      around the oral sucker, a blind ending H-shaped intestine and a deeply lobed
      ovary.

PMID- 16969714
TI  - The diversity and complexity of the cyanobacterial thioredoxin systems.
AB  - Cyanobacteria perform oxygenic photosynthesis, which makes them unique among the
      prokaryotes, and this feature together with their abundance and worldwide
      distribution renders them a central ecological role. Cyanobacteria and
      chloroplasts of plants and algae are believed to share a common ancestor and the
      modern chloroplast would thus be the remnant of an endosymbiosis between a
      eukaryotic cell and an ancestral oxygenic photosynthetic prokaryote. Chloroplast
      metabolic processes are coordinated with those of the other cellular compartments
      and are strictly controlled by means of regulatory systems that commonly involve
      redox reactions. Disulphide/dithiol exchange catalysed by thioredoxin is a
      fundamental example of such regulation and represents the molecular mechanism for
      light-dependent redox control of an ever-increasing number of chloroplast
      enzymatic activities. In contrast to chloroplast thioredoxins, the functions of
      the cyanobacterial thioredoxins have long remained elusive, despite their common
      origin. The sequenced genomes of several cyanobacterial species together with
      novel experimental approaches involving proteomics have provided new tools for re
      examining the roles of the thioredoxin systems in these organisms. Thus, each
      cyanobacterial genome encodes between one and eight thioredoxins and all
      components necessary for the reduction of thioredoxins. Screening for thioredoxin
      target proteins in cyanobacteria indicates that assimilation and storage of
      nutrients, as well as some central metabolic pathways, are regulated by
      mechanisms involving disulphide/dithiol exchange, which could be catalysed by
      thioredoxins or related thiol-containing proteins.

PMID- 16969715
TI  - Proteomic profiles of thylakoid membranes and changes in response to iron
      deficiency.
AB  - The proteomic profile of thylakoid membranes and the changes induced in that
      proteome by iron deficiency have been studied by using thylakoid preparations
      from Beta vulgaris plants grown in hydroponics. Two different 2-D electrophoresis
      approaches have been used to study these proteomes: isoelectrical focusing
      followed by SDS PAGE (IEF-SDS PAGE) and blue-native polyacrylamide gel
      electrophoresis followed by SDS PAGE (BN-SDS PAGE). These techniques resolved
      approximately 110-140 and 40 polypeptides, respectively. Iron deficiency induced
      significant changes in the thylakoid sugar beet proteome profiles: the relative
      amounts of electron transfer protein complexes were reduced, whereas those of
      proteins participating in leaf carbon fixation-linked reactions were increased. A
      set of polypeptides, which includes several enzymes related to metabolism, was
      detected in thylakoid preparations from Fe-deficient Beta vulgaris leaves by
      using BN-SDS PAGE, suggesting that they may be associated with these thylakoids
      in vivo. The BN-SDS PAGE technique has been proven to be a better method than IEF
      SDS PAGE to resolve highly hydrophobic integral membrane proteins from thylakoid
      preparations, allowing for the identification of complexes and determination of
      their polypeptidic components.

PMID- 16969716
TI  - Down co-regulation of light absorption, photochemistry, and carboxylation in Fe
      deficient plants growing in different environments.
AB  - The regulation of photosynthesis through changes in light absorption,
      photochemistry, and carboxylation efficiency has been studied in plants grown in
      different environments. Iron deficiency was induced in sugar beet (Beta vulgaris
      L.) by growing plants hydroponically in controlled growth chambers in the absence
      of Fe in the nutrient solution. Pear (Pyrus communis L.) and peach (Prunus
      persica L. Batsch) trees were grown in field conditions on calcareous soils, in
      orchards with Fe deficiency-chlorosis. Gas exchange parameters were measured in
      situ with actual ambient conditions. Iron deficiency decreased photosynthetic and
      transpiration rates, instantaneous transpiration efficiencies and stomatal
      conductances, and increased sub-stomatal CO(2) concentrations in the three
      species investigated. Photosynthesis versus CO(2) sub-stomatal concentration
      response curves and chlorophyll fluorescence quenching analysis revealed a non
      stomatal limitation of photosynthetic rates under Fe deficiency in the three
      species investigated. Light absorption, photosystem II, and Rubisco carboxylation
      efficiencies were down-regulated in response to Fe deficiency in a coordinated
      manner, optimizing the use of the remaining photosynthetic pigments, electron
      transport carriers, and Rubisco.

PMID- 16969717
TI  - Inhibition of photosystem II photochemistry by Cr is caused by the alteration of
      both D1 protein and oxygen evolving complex.
AB  - The effect of chromium (Cr) on photosystem II (PSII) electron transport and the
      change of proteins content within PSII complex were investigated. When Lemna
      gibba was exposed to Cr during 96 h, growth inhibition was found to be associated
      with an alteration of the PSII electron transport at both PSII oxidizing and
      reducing sides. Investigation of fluorescence yields at transients K, J, I, and P
      suggested for Cr inhibitory effect to be located at the oxygen-evolving complex
      and Q(A) reduction. Those Cr-inhibitory effects were related to the change of the
      turnover of PSII D1 protein and the alteration of 24 and 33 kDa proteins of the
      oxygen-evolving complex. The inhibition of the PSII electron transport and the
      formation of reactive oxygen species induced by Cr were highly correlated with
      the decrease in the content of D1 protein and the amount of 24 and 33 kDa
      proteins. Therefore, functional alteration of PSII activity by Cr was closely
      related with the structural change within PSII complex.

PMID- 16969718
TI  - Calculating measures of biological interaction using R.

PMID- 16969719
TI  - Conditions in utero and cancer risk.
AB  - There is increasing recognition that conditions in utero are of importance for
      later cancer risk in several organs, particularly the testis and breast. A review
      of the most recent literature on this topic is therefore warranted. The PubMed
      database was searched for relevant recent literature on intrauterine conditions
      associated with cancer risk later in life, with particular emphasis on the
      testis, breast, but also studies pertaining to other organs were included.
      Epidemiological and experimental data support the hypothesis that factors acting
      in utero play a role in the development of cancer in the testis and breast. For
      other organs, such as the prostate, urinary system and colorectum, the results
      are inconclusive. While conditions during foetal life are associated with later
      cancer risk in the testis and breast, the biological mechanisms are for the most
      part elusive. They are, however, likely to involve hormonal disturbances, number
      of cells at risk, and genetic or epigenetic events.

PMID- 16969720
TI  - Recognition and elimination of diversified pathogens in insect defense systems.
AB  - The elimination of infectious non-self by the host defense systems of
      multicellular organisms requires a variety of recognition and effector molecules.
      The diversity is generated in somatic cells or encoded in the germ-line. In
      adaptive immunity in jawed vertebrates, the diversity of immunoglobulins and
      antigen receptors is generated by gene rearrangements in somatic cells. In innate
      immunity, various effector molecules and pattern recognition receptors, such as
      antimicrobial peptides and peptidoglycan recognition proteins, are encoded in the
      germ-line of multicellular organisms, including insects and jawed vertebrates. In
      the present review, we discuss how insect host defense systems recognize and
      eliminate a multitude of microbes via germ-line-encoded molecules, including
      recent findings that a Drosophila member of the immunoglobulin superfamily is
      extensively diversified by alternative splicing in somatic immune cells and
      participates in the elimination of bacteria.

PMID- 16969721
TI  - The changing of the guard: Molecular diversity and rapid evolution of beta
      defensins.
AB  - Defensins are small cationic peptides involved in innate immunity and are
      components of the first line of defence against invading pathogens. beta
      defensins are a subgroup of the defensin family that display a particular
      cysteine spacing and pattern of intramolecular bonding. These molecules are
      produced mostly by epithelia lining exposed surfaces and appear to have both
      antimicrobial and cell signalling functions. The unusually high degree of
      sequence variation in the mature peptide produced by the paralogous and in some
      cases orthologous genes implies extensive specialisation and species specific
      adaptation. Here we review recent functional data that are an important addition
      to our knowledge of the innate immune response and novel antibiotic design. We
      also consider the organisation and evolution of the genomic loci harbouring these
      genes where radical and rapid changes in beta-defensin sequences have been shown
      to result from the interplay of both positive and negative selection.
      Consequently these genes provide some unusually clear glimpses of the processes
      of duplication and specialisation that have shaped the mammalian genome.

PMID- 16969723
TI  - Web-based diagnostic imaging service using XML forms.
AB  - Traditionally, radiology has been conceived as a support department providing
      patient scanning services to the other clinical departments in a hospital.
      However, recent advancements in networking technology and related information
      systems such as picture archiving and communication system (PACS) and radiology
      information system (RIS) provide new opportunities for inventing different types
      of diagnostic imaging businesses such as teleradiology. In this article, we
      examined the business processes of currently operating imaging centers and
      proposed a prototype of an information system that can facilitate their workflows
      in a more efficient way. The principal component of our proposed system is a
      report management module built on extensible markup language (XML) technologies
      that allows much flexibility and convenience for both imaging technicians and
      radiologists.

PMID- 16969724
TI  - Patient exam data reconciliation tool.
AB  - Since the introduction of Picture Archiving and Communications Systems (PACS)
      into the medical radiology community, the efficiency and workflow of radiology
      departments adopting this technology has been improved to a degree much greater
      than initially anticipated. Although technological advances fuel efficiency and
      improve workflow, medical mistakes become prevalent as a result. This observation
      underscores the need for active measures by PACS quality assurance personnel to
      prevent human and machine errors from contributing to the total of avoidable
      medical errors, particularly in the area of diagnostic imaging.

PMID- 16969725
TI  - [Right atrial ablation of ectopic atrial tachycardia using a 20-pole mapping
      catheter].
AB  - INTRODUCTION: Ectopic atrial tachycardia (EAT) are frequently unresponsive to
      pharmacological antiarrhythmic therapy. Radiofrequency ablation seems to be a
      safe approach to treat those arrhythmias. In the present study we report our
      results of radiofrequency ablation of EAT with a new mapping system (Stablemapr,
      Medtronic). METHODS: Thirty consecutive patients with right atrial tachycardia
      were included in the study. In 15 patients (G1) the 20-polar Stablemapr was used
      for localization of the arrhythmia foci. Data were compared with a control group
      (G2, n=15), in which mapping was performed conventionally. The demographic
      characteristics and the distribution of the different cardiac diseases were
      comparable in both groups. In group 1 the identification of the EAT was
      facilitated by the placement of the 20-pole mapping catheter in the right atrium.
      In group 2 point by point measurements were performed to find the earliest local
      atrial activation compared to a reference electrode in the high right atrium
      (activation mapping), or foci were identified by analysis of the P-wave
      morphology during stimulation (pacemapping). RESULTS: It was possible to
      successfully ablate all atrial tachycardias. The distribution of the foci was
      similar in both groups (G1/G2): near to the superior (3/5) and inferior (1/0)
      caval vene ostium, on the free wall (3/3), at the coronary sinus ostium (3/3) and
      on the interatrial septum (5/4). The mean procedure (G1: 88+/-33 vs G2: 151+/-61
      min; p= or <0.05) and fluoroscopic times (G1: 19+/-9 vs G2: 38+/-28 min; p= or
      <0.05) were significantly shorter in group 1. Moreover, the mean number of
      radiofrequency applications was reduced significantly by using the new mapping
      system (G1: 10+/-10 vs G2: 16+/-13; p= or <0.05). CONCLUSION: Radiofrequency
      ablation of EAT with right atrial focus can be performed safely and successfully
      using a 20-pole mapping catheter. The greatest advantages compared to
      conventional mapping and ablation strategies lies in the shortened investigation
      and fluoroscopic time.

PMID- 16969722
TI  - The RNase a superfamily: generation of diversity and innate host defense.
AB  - The Ribonuclease A superfamily includes an extensive network of distinct and
      divergent gene lineages. Although all ribonucleases of this superfamily share
      invariant structural and catalytic elements and some degree of enzymatic
      activity, the primary sequences have diverged significantly, ostensibly to
      promote novel function. We will review the literature on the evolution and
      biology of the RNase A ribonuclease lineages that have been characterized
      specifically as involved in host defense including: (1) RNases 2 and RNases 3,
      also known as the eosinophil ribonucleases, which are rapidly-evolving cationic
      proteins released from eosinophilic leukocytes, (2) RNase 7, an anti-pathogen
      ribonuclease identified in human skin, and (3) RNase 5, also known as angiogenin,
      another rapidly-evolving ribonuclease known to promote blood vessel growth with
      recently-discovered antibacterial activity. Interestingly, some of the
      characterized anti-pathogen activities do not depend on ribonuclease activity per
      se. We discuss the ways in which the anti-pathogen activities characterized in
      vitro might translate into experimental confirmation in vivo. We will also
      consider the possibility that other ribonucleases, such as the dimeric bovine
      seminal ribonuclease and the frog oocyte ribonucleases, may have host defense
      functions and therapeutic value that remain to be explored. (190 words).

PMID- 16969726
TI  - [TEE-guided cardioversion in patients with atrial fibrillation without previous
      anticoagulation].
AB  - A total of 332 patients (mean age 65+/-10 years, 86 female) with nonvalvular
      atrial fibrillation (AF) of more than 48 hours duration and lack of a sufficient
      anticoagulation were included. After exclusion of thrombotic material in the left
      atrium using transesophageal echocardiography (TEE) cardioversion (CV) was
      performed within 24 hours. At the same time oral anticoagulation (AC)
      (overlapping with PTT-affecting heparinisation) was started. If thrombi were
      found by TEE, the examination was repeated after at least four weeks of
      anticoagulation. If thrombi were absent at this time, CV was performed.
      Periprocedural embolism was defined as primary endpoint, whereas the detection of
      atrial thrombi before CV was defined as secondary endpoint. In 33 of the 332
      Patients (9.9%) the TEE showed a thrombus in the left atrium respectively the
      left atrial appendage (n=22) or thrombi could not be excluded (n=11). 383 TEEs
      were performed without complications in an overall of 332 patients.A total of 305
      CV were performed (electrical n=300, pharmacological n=5) and during
      periprocedural monitoring and in the time of four weeks after CV no
      thromboembolic complications were observed.TEE-guided CV in patients with AF
      persisting for more than 48 hours and without previous AC can be considered as a
      method that is both safe and effective.

PMID- 16969727
TI  - [Atrial myocardial perforation due to catheter ablation of the cavotricuspid
      isthmus].
AB  - A 79-year-old man died 3.5 hours after catheter ablation of atrial fibrillation
      due to pericardial tamponade. Autopsy and consecutive microscopic examinations
      furnished evidence of electrothermical necroses topographically arranged
      regularly adjacent to the pulmonary veins in the left atrium and across the area
      of the isthmus in the right atrium with a rupture of the right atrial wall in the
      area of a coagulation spot. The post-mortem findings and pathogenetic
      considerations for the delayed pericardial tamponade are discussed.

PMID- 16969728
TI  - Inappropriate ICD discharge induced by electrical interference from a physio
      therapeutic muscle stimulation device.
AB  - This report illustrates the case of a patient with an implantable cardioverter
      defibrillator (ICD) who during physiotherapy with transcutaneous electrical
      stimulation of the lumbar musculature perceived a shock discharge by the ICD.
      Analysis of the stored electrogram showed inappropriate therapy due to
      electromagnetic interference with the external stimulation. Patients as well as
      physiotherapists should be informed about this potential interaction to avoid
      such iatrogenic, inappropriate ICD therapy.

PMID- 16969729
TI  - [The 100(th) anniversary of "The Conduction System of the Mammalian Heart" by
      Sunao Tawara].
AB  - In 1906, Sunao Tawara published "Das Reizleitungssystem des Saugetierherzens"
      ("The Conduction System of the Mammalian Heart"). We remind of the centennial of
      this publication, really a morphological study, as it is a milestone of cardiac
      electrophysiology, too. Tawara not only described for the first time all
      compartments of the atrioventricular conduction as a continuous system but also
      derived its function from the morphological pecularities. Later, this was
      confirmed by physiological experiments. The significance of Tawara's discovery
      can be seen from reactions to his monograph documented in the contemporary
      literature.

PMID- 16969730
TI  - [Annual report 2004 of the German cardiac pacemaker registry].

PMID- 16969731
TI  - [Difficult AV optimization in a patient with a biventricular implantable
      cardioverter defibrillator].
AB  - This quiz presents the case of a patient who deteriorated clinically after AV
      delay optimization of a biventricular implantable cardioverter defibrillator. It
      illustrates that these complex devices require profound knowledge of their
      function.

PMID- 16969732
TI  - [Higher, faster--but not recurring].

PMID- 16969737
TI  - Mechanisms of injury in hypoxic-ischemic encephalopathy: implications to therapy.
AB  - Cardiac arrest survivors commonly suffer ischemic brain injury, and understanding
      the mechanisms of injury is essential to providing insight for effective
      therapies for brain protection. Injury can occur at the time of the cardiac
      arrest and is dependent not only on the duration but also the degree of impaired
      circulation. Injury can be ongoing even after the return of spontaneous
      circulation, giving the clinician an additional window of opportunity to treat
      and protect the injured brain. This section will review the molecular basis of
      injury with cardiac arrest and will elucidate the different mechanisms of injury
      between cardiac arrest, pure respiratory arrest, and arrest secondary to toxins
      (e.g., carbon monoxide). The rationale for multiple postarrest therapies, such as
      hypothermia and induced hypertension, will also be reviewed.

PMID- 16969738
TI  - Prehospital interventions to improve neurological outcome following cardiac
      arrest.
AB  - As many cases of cardiac arrest occur outside of the health care setting,
      prehospital treatment may dramatically affect patient outcomes. The three major
      interventions that have been studied are chest compressions and ventilation,
      electrical defibrillation, and medications. Recent studies show that increasing
      the rate of cardiopulmonary resuscitation (CPR), decreasing the rate of
      ventilation, and initiation of CPR prior to defibrillation may result in improved
      survival. Biphasic defibrillators can restore perfusing rhythms while minimizing
      myocardial injury. Public access to automatic defibrillators has been shown to
      increase the survival of cardiac arrest patients. Medications such as amiodarone,
      vasopressin, and thrombolytics also may have a role in the prehospital treatment
      of cardiac arrest. Recent advances in these areas will be reviewed with a
      discussion of the effect of each intervention on the restoration of circulation
      and neurological outcomes.

PMID- 16969739
TI  - Therapeutic hypothermia for brain injury after cardiac arrest.
AB  - Morbidity and mortality in patients successfully resuscitated from cardiac arrest
      primarily depends on neurological outcome. Clinical trials of therapies directed
      toward reducing the extent of neuronal damage by means of pharmacological agents
      have been disappointing. To date, the only clinically effective tool for
      amelioration of brain damage by ischemia and reperfusion is mild to moderate
      induced hypothermia. The pathophysiology of global hypoxic-ischemic brain injury,
      the mechanisms by which hypothermia confers neuroprotection, and the encouraging
      beneficial effects of mild to moderate hypothermia in experimental studies and
      clinical trials are discussed.

PMID- 16969741
TI  - Electrophysiological prognostication and brain injury from cardiac arrest.
AB  - Anoxic coma after cardiorespiratory arrest warrants precocious investigation to
      establish probable outcome. Electroencephalogram (EEG) may uncover subclinical
      seizures; EEG grades have provided accurate prognosis of poor and favorable
      outcomes, but are weakest in those patients in between. Somatosensory evoked
      potentials now have proven benefit in accurately establishing a poor outcome
      (death or persistent vegetative state) when cortical responses (N20) are absent.
      These studies are particularly helpful when clinical examination of coma, early
      on, might yield uncertain prognosis (i.e., when brain stem reflexes are present).
      Combining clinical examination with electrophysiology has increasingly yielded
      multimodality approaches to early prognostication of coma after cardiorespiratory
      arrest, with more recent studies using event-related and middle-latency
      potentials showing promise for distinguishing good outcome (to consciousness),
      from awake but vegetative states. Further studies are warranted for this
      multimodality approach which, hopefully, may yield more widespread practical use
      of these testing modalities.

PMID- 16969740
TI  - Postresuscitative intensive care: neuroprotective strategies after cardiac
      arrest.
AB  - Cardiac arrest is a common disease in the United States, and many patients will
      die as a result of the neurological damage suffered during the anoxic period, or
      will live in a neurologically debilitated state. When cardiopulmonary-cerebral
      resuscitation results in the return of spontaneous circulation, intensive care is
      required to optimize neurological recovery. Such "brain-oriented" therapies
      include routine care, such as positioning and maintenance of volume status;
      optimization of cerebral perfusion, with the use of vasopressors if needed;
      management of increased intracranial pressure with agents such as hypertonic
      saline; assuring adequate oxygenation and avoiding hypercapnia; aggressive fever
      control; intensive glucose control, with the use of an insulin drip if needed;
      and management of seizures if they occur. To date, no neuroprotectant medications
      have been shown to improve neurological outcome. Induced moderate therapeutic
      hypothermia is utilized as a neuroprotective maneuver. Future treatment options
      and advanced monitoring techniques are also discussed. Further study to optimize
      neuroprotective strategies when treating patients who survive cardiac arrest is
      needed.

PMID- 16969742
TI  - Biomarkers and neuroimaging of brain injury after cardiac arrest.
AB  - Unfortunately, it remains a difficult task to predict with certainty which
      patients will have a poor neurological outcome following cardiac arrest. Finding
      a quantitative prognostic model of outcome has become the objective of many
      intensivists to assist grieving families in making early difficult decisions
      regarding withdrawal of life support. An ideal prognostic test should be readily
      available, easily reproducible, and associated with a high degree of specificity
      for poor outcome. The goal is not to define which patients may recover, but
      rather which patients have no likelihood of meaningful neurological recovery at
      all to justify early withdrawal of support. The literature and the role of
      biochemical markers in the blood and in the cerebrospinal fluid will be evaluated
      as prognosticators following cardiac arrest. Radiological indicators of anoxic
      cerebral damage are reviewed. Each serum or radiological marker has its pros and
      cons. To accurately prognosticate following cardiac arrest, a multimodal scale or
      algorithm that incorporates serum markers, radiological markers, and the
      neurological exam is clearly needed. As these techniques are being evaluated more
      closely and as imaging modalities increase in sensitivity and portability,
      physicians will continue to assist families by providing some guidance as to
      which patients have no chance of meaningful recovery.

PMID- 16969743
TI  - Long-term neurological complications after hypoxic-ischemic encephalopathy.
AB  - Hypoxic-ischemic encephalopathy accompanying cardiac arrest is a common cause of
      long-term neurological dysfunction. With the improvement in prehospital emergency
      systems, larger numbers of people are resuscitated from cardiac arrests, although
      with the increased prospect of neurological sequelae. Neurological impairment
      after cardiac arrest is dependent on the degree of brain damage suffered during
      the arrest. Although the duration and severity of brain ischemia is often
      difficult to determine, clinicians are often faced with difficult issues related
      to predicting outcome related to awakening and long-term neurological deficits
      after the arrest. Neurological impairments range from mild cognitive deficits to
      severe motor and cognitive deficits that preclude independence in many activities
      of daily living. Several neurological syndromes have been described in patients
      who awaken from hypoxic-ischemic coma with lasting motor and cognitive deficits.
      This review will address many of the common syndromes after hypoxic-ischemic
      encephalopathy, including persistent vegetative states, seizures, myoclonus,
      movement disorders, cognitive dysfunction, and other neurological abnormalities.

PMID- 16969744
TI  - Brain injury from cardiac bypass procedures.
AB  - Patients who undergo coronary artery bypass grafting (CABG) are at increased risk
      for brain injury. Surgical techniques have advanced so that the risk of
      neurological sequelae is decreased, but there remains significant morbidity and
      mortality related to the postoperative period as well as to the surgery itself.
      In addition, patients who undergo CABG have comorbidities or demographic factors
      that may increase their likelihood of developing neurological complications.
      Pathophysiological mechanisms of cerebral injury after CABG range from
      hemodynamic compromise to embolization, either intraoperatively or
      postoperatively. Biochemical markers such as S100 and neuron-specific enolase may
      play a role in the prediction of outcome after CABG, and because of this may help
      elucidate other potential risk factors. Specific neurological sequelae are
      discussed, such as stroke, with summaries of the apparent risk factors, as well
      as encephalopathy, seizure, and both short- and long-term cognitive deficits.
      Changes in surgical technique have led to some improvements, but there is no
      definitive information yet as to the role of some of these, such as the use of
      off-pump CABG. Other techniques such as the use of an arterial filter are
      discussed, as are their potential benefits in the prevention of neurological
      complications.

PMID- 16969745
TI  - The spectrum of encephalopathy in critical illness.
AB  - Beyond the cerebral impact of cardiac arrest, recent research indicates a high
      prevalence of neurological disturbances such as delirium and coma among patients
      admitted to the intensive care unit (ICU). These disturbances, grouped here under
      the term "encephalopathy," may be overlooked while attention is devoted to
      reversing life-threatening imbalances in cardiac and pulmonary function.
      Nevertheless, there is ample evidence that encephalopathy is an independent
      predictor of mortality. Factors associated with encephalopathy include primary
      cerebral disorders such as stroke, trauma, and meningitis, or systemic
      derangements including sepsis, organ failure, and exposure to pharmacological
      agents and toxins. Although encephalopathy may resolve with treatment of the
      underlying disorder, there is mounting evidence that cerebral dysfunction
      persists beyond the acute phase of critical illness. ICU survivors often suffer
      chronic impairments in cognitive ability, suggesting occult brain injury. The
      pathogenesis and natural history of encephalopathy, still poorly understood, need
      further clarification to spur the development of effective preventive and
      therapeutic interventions.

PMID- 16969746
TI  - Ethical issues in critical care and cardiac arrest: clinical research, brain
      death, and organ donation.
AB  - Cardiac arrest results in global hypoxic-ischemic brain injury from which there
      is a range of possible neurological outcomes. In most cases, patients may require
      a surrogate to make decisions regarding end-of-life care, including the
      withdrawal of life-sustaining therapies. This article reviews ethical
      considerations that arise in the clinical care of patients following cardiac
      arrest, including decisions to continue or withdraw life-sustaining therapies;
      brain death determination; and organ donation in the context of brain death and
      cardiac death (so-called non-heart-beating donation). This article also discusses
      ethical concerns pertaining to the design and conduct of resuscitation research
      that is necessary for the development of effective therapies to prevent anoxic
      brain injury or promote neurological recovery.

PMID- 16969747
TI  - PMMA versus titanium cage after anterior cervical discectomy - a prospective
      randomized trial.
AB  - INTRODUCTION: Nonautologous interbody fusion materials are utilised in increasing
      numbers after anterior cervical disc surgery to overcome the problem of donor
      site morbidity of autologous bone grafts. This study investigates the performance
      of two nonautologous materials, the bone cement Polymethylmethacrylate (PMMA) and
      titanium cages. This prospective randomised trial, with assessment of the results
      by an independent observer, evaluates whether a Polymethylmethacrylate (PMMA)
      spacer or a titanium cage provides a better fusion rate around the implant and a
      better clinical outcome. PATIENTS/MATERIAL AND METHODS: Between 2000 and 2002,
      115 patients with monoradicular cervical nerve root compression syndrome caused
      by soft cervical disc herniation were eligible for this study. Myelopathy,
      excessive osteophyte formation, and adjacent level degeneration were exclusion
      criteria. A block-restricted randomisation was applied. The 2-year clinical
      outcome served as the primary endpoint of the study. Clinical outcome was
      assessed according to the Odom scale by an independent observer at the follow-up
      examination. Preoperative, postoperative, and follow-up radiographs were taken.
      RESULTS: The study was completed by 107 patients (53 with PMMA and 54 with
      titanium cage). No significant difference between the two groups could be
      established with respect to the clinical outcome. In each group, 26 patients
      scored excellent. Good results were found in 19 PMMA patients and 16 titanium
      cage patients; satisfactory results were found in 8 PMMA patients and 9 titanium
      cage patients; bad results were found in 3 titanium cage patients. In 47 titanium
      cage cases (87%), fusion occurred radiologically as bony bridging around the
      implant. The fusion rate was significantly lower (p=0.011) in the PMMA group,
      with 35 cases (66%) united at follow-up. CONCLUSION: The radiological result of
      the titanium cage is superior to that of PMMA with respect to the fusion rate.
      Although the titanium cage achieves a better fusion rate, there is no difference
      between titanium cages and PMMA with respect to the clinical outcome.

PMID- 16969749
TI  - Elderly patients in the intensive care unit: Ideal candidates for multiple organ
      failure.

PMID- 16969748
TI  - Clinical evidence for the cardiovascular benefits of angiotensin receptor
      blockers.
AB  - Targeting the renin-angiotensin-aldosterone system (RAAS), specifically the
      effector peptide angiotensin II (Ang II), represents a major opportunity for
      slowing the progression of cardiovascular disease (CVD) and, in turn, reducing
      the risk of morbidity and mortality. Inhibition of angiotensin-converting enzyme
      (ACE) and selective blockade of Ang II AT1 receptors are two approaches through
      which the pathophysiological effects of Ang II can be targeted. Numerous clinical
      studies have established the benefits of ACE inhibitors (ACE-Is) in lessening the
      morbidity and mortality burden of CVD. There are, however, tolerability concerns
      associated with ACE-Is, such as angioedema and dry cough. By blocking Ang II at
      the AT1 receptor level, Ang II receptor blockers (ARBs) provide a more specific
      and complete blockade of the deleterious effects of Ang II and tend to have more
      favourable tolerability. A number of clinical trials have shown that ARBs are not
      only associated with positive outcomes across the CVD continuum but mat also have
      a role in the prevention or delay of diabetes (a major cardiovascular risk
      factor). Ongoing trials are aiming to define the place of such agents in
      lessening morbidity and mortality from CVD.

PMID- 16969750
TI  - Coronary artery calcification, common carotid artery intima-media thickness and
      aortic pulse wave velocity in patients on peritoneal dialysis.
AB  - An increasing body of evidence suggests that atherosclerosis in patients with
      uremia differs from that found in general population in terms of advancement and
      localization of vascular lesions. It has also been suggested that different non
      invasive techniques of vascular system evaluation are designed to show different
      types of lesions (i.e. vascular calcification, stiffness or 'classical'
      atherosclerosis). The aim of the study was to search for possible associations
      between results obtained with three different non-invasive methods of vascular
      system assessment in three different vascular sites in patients treated with
      peritoneal dialysis (PD). 61 patients (28 F, 33 M), mean age of 50.4+/-13.6
      years, on maintenance PD for a median period of 10 months (range 1-96 months)
      were included. Coronary artery disease (CAD) was present in 21 subjects. In all
      subjects coronary artery calcification score (CaSc) using multi-row spiral
      computed tomography (MSCT), aortic pulse wave velocity (AoPWV) and ultrasound
      based common carotid artery intima-media thickness (CCA-IMT) were performed as
      methods for assessing coronary calcium burden, arterial stiffness and
      atherosclerosis, respectively. Median value of CaSc equaled 11.5 Agatston units
      (range 0-5502.8 units). Median AoPWV was 10.4 m/s (range 7.56-18.1 m/s), and
      median CCA-IMT-0.6 mm (range 0.3-1.0 mm). In 16 patients (26.2%) at least one
      plaque in at least one common carotid artery was found on ultrasound. CaSc
      correlated with AoPWV (R=0.32, p<0.01) and with CCA-IMT (R=0.35, p<0.005),
      whereas no association was found between AoPWV and CCA-IMT. AoPWV, but not CaSc
      nor IMT correlated with blood pressure. The values of CCA-IMT and AoPWV increased
      together with consecutive Agatston categories (with p<0.001 for differences in
      AoPWV and p<0.05 for CCA-IMT). Patients with at least one plaque found in at
      least one CCA and patients with CAD were characterized with significantly higher
      values of CaSc, IMT and PWV, when compared to plaque-free and CAD- negative
      subjects, respectively. Association between CaSc and both IMT and PWV may suggest
      that the mechanism of three assessed vascular pathologies may be based, to some
      extent, on the process of pathologic calcium-phosphate deposition. Lack of
      correlation found between PWV and IMT may suggest that aortic stiffness and
      carotid atherosclerosis may partially differ in their pathologic background
      and/or are dissociated in time.

PMID- 16969751
TI  - Role of B-type natriuretic peptide in cardiovascular state monitoring in a
      hemodialysis patient with primary amyloidosis.
AB  - BACKGROUND: Cardiac involvement occurs in up to 50% of patients with primary or A
      amyloidosis (ALA) and is associated with very poor prognosis. B-type natriuretic
      peptide (BNP) has been proposed as a guide for treatment of heart failure
      patients and as an index of myocardial dysfunction in patients with ALA. Data
      about BNP dosage for cardiovascular monitoring of patients with ALA on renal
      replacement therapy are lacking. CASE: A 64 year old Caucasian man was admitted
      because of nephrotic syndrome in July 2003. Renal diagnosis was ALA. Melphalan
      and prednisolone were given but renal function worsened and in April 2004
      standard bicarbonate hemodialysis was started. In March 2004 thalidomide was
      added to his therapy. During the follow-up ejection fraction was stable and was
      65% on the contrary E/A ratio gradually increased and overtook 1. BNP plasma
      levels were increased and the values recorded during the follow-up were: 2505
      pg/mL in October 2003 (normal reference values<100), 1827 in April 2004, 4006 in
      June 2004, 5000 in September 2004, 3750 in January 2005 and 1920 in April 2005.
      In September 2005 BNP was 3380 pg/mL. The patient was still alive after a follow
      up longer than two years. CONCLUSION: In ALA patients a powerful prognostic role
      of BNP has been reported whose expression is increased in ventricular myocytes of
      patients with cardiac involvement. BNP level monitoring does not appear to be
      superior to standard echocardiography in evaluating cardiovascular status of
      uremic patients with ALA.

PMID- 16969752
TI  - A small scale oxygenator for cardiopulmonary bypass in rats.
AB  - Cardiopulmonary bypass (CPB) devices replace transiently the function of both
      heart and lungs, allowing the investigator to work safely on a stopped heart.
      Although this technology has greatly improved since its first applications in the
      early 1950's there is still no definitive rat CPB model, various experiments
      reporting drawbacks like pulmonary edema, large priming volumes,etc. We present a
      new oxygenator that can be used in cardiopulmonary bypass experiments in rats,
      simple in design and efficient in function,in which the process of blood
      oxygenation takes place in a vertical cylinder filled up with air or oxygen, with
      blood being spread onto the wall and then trickling down in a thin layer that
      facilitates the oxygen transfer. The oxygenation is efficient, the pO2 reaches
      levels of almost 150 mmHg (physiological level is around 100 mmHg) in conditions
      of oxygen saturation of over 99% (normal levels 95%-98%).

PMID- 16969753
TI  - Mechanical properties of alginate beads hosting hepatocytes in a fluidized bed
      bioreactor.
AB  - Fluidized bed bioartificial liver has been proposed as a temporary support to
      bridge patients suffering from acute liver failure to transplantation. In such a
      bioreactor, alginate beads hosting hepatocytes are in continuous motion during at
      least six hours. After having shown in vitro the functionality of such a device,
      the present study aims at analyzing the potential mechanical alterations of the
      beads in the bioreactor, perfused by different surrounding media. Compression
      experiments are performed and coupled for analysis with Hertz theory. They
      provide qualitative and quantitative data. The average value of the shear
      modulus, calculated for the different cases studied varied from 2.4 to 10.4 kPa,
      and could therefore be considered as a quantitative measure of the beads
      mechanical properties. From the compression experiments and the estimated values
      of the shear modulus, we could now evaluate the effect of different operating
      conditions (fluidization, presence of cells, surrounding medium) on the
      mechanical behavior of alginate beads. On the one hand, the motion during six
      hours in the bioreactor does not alter the beads significantly. On the other
      hand, the presence of different substances in the fluid phase might change their
      mechanical strength. These results can be considered as new encouragements to use
      such a device as a bioartificial organ.

PMID- 16969754
TI  - 'UroMaix' scaffolds: novel collagen matrices for application in tissue
      engineering of the urinary tract.
AB  - Reconstruction of bladder and ureter tissue is indicated in cases of injury,
      stenosis, infection or tumor. Substitution by ileum, colon or pure synthetic
      polymers generates a variety of complications. Biohybrid tissue mimicking
      structural and functional attributes of the multilayered wall architecture of the
      urinary conduit may be the solution to current problems. This study reports on
      porcine urinary tract cells isolated and placed on UroMaix matrices with
      different degrees of cross-linking produced from highly purified type I collagen
      from medically approved porcine tissue. A patented procedure revealed membrane
      structures composed of a dense fibrous side and an open fibrous side. These
      scaffolds with the porcine urinary tract cells were incubated in a batch culture
      system for up to 14 days. Cell growth and topographical orientation were
      examined. Urothelial cells showed maximum attachment and a significant increase
      of living cells on the dense fiber layer of UroMaix-1. No attachment of
      urothelial cells occurred on the other prototypes. Smooth muscle cells showed
      similar behavior within the open fiber layer of all UroMaix matrices. Both
      urothelial and smooth muscle cells retained their phenotypes as demonstrated by
      the immunostaining of epithelial cytokeratin 18 and the smooth muscle myosin
      heavy chain respectively. Thus we could show that UroMaix scaffolds support the
      attachment and proliferation of urinary tract cells. The elastomeric properties
      of the collagenous matrices promise attractive applications in the tissue
      engineering of the urinary tract with its high mechanical demands.

PMID- 16969755
TI  - A new chemical etching process to improve endosseous implant osseointegration: in
      vitro evaluation on human osteoblast-like cells.
AB  - The development of novel mechanical and chemical surface modification treatments
      to improve the osteointegration properties of osseointegrated dental implants is
      nowadays a topic of great applicative interest. The aim of the present study was
      to analyse the role of surface topography and chemistry of four different surface
      treatments on titanium by an in vitro human osteosarcoma immortalised cell line
      model (MG63). The surface treatments considered were (a) machined titanium, (b)
      chemical etched on machined titanium, (c) sandblasted titanium and (d) chemical
      etching on sandblasted titanium. Chemical and physical surface properties were
      investigated by Scanning Electron Microscopy, Thin Film-X ray Diffraction and by
      Laser Profilometry. The in vitro biological response was characterised using the
      MG63 cell line by elution cytotoxicity tests, cell morphology, adhesion,
      proliferation activity, alkaline phosphatase activity and total DNA content in
      order to show a relationship between osteoblast response and surface features.
      Chemical and physical characterisation showed that the considered treatments
      differently modify the surface morphology in the micro and sub-micrometric scale.
      Although some differences in alkaline phosphatase activity were observed in the
      biological characterisation, depending on the specific material's surface
      finishing, the results showed that cells were well responsive on all the tested
      materials and grew and differentiated with similar proliferation rate.

PMID- 16969756
TI  - Antigen clearing from porcine heart valves with preservation of structural
      integrity.
AB  - Bioprostheses currently used for replacement of diseased cardiovascular tissue
      are preserved and partially protected from immune rejection through chemical
      fixation. However, after implantation, chemically preserved (fixed) material has
      limited durability and lacks the ability to revitalize through cellular ingrowth
      and remodeling. As an alternative to fixation, we aimed at thoroughly removing
      antigens from tissue, leaving an intact scaffold, suitable for integration and
      revitalization in the host. Extensive washing of porcine heart valves with a
      mixture of two detergents (SDS and Triton X-100) yielded an intact matrix devoid
      of cells and depleted of soluble proteins that was minimally immunogenic in
      rabbits. A detailed characterization of the biomechanics and durability of the
      tissue is under way. If the lack of immunogenicity is confirmed in primates, our
      results would suggest that a detergent-washed, unfixed porcine heart valve can be
      an attractive non-inflammatory scaffold for heart valve regeneration in humans.

PMID- 16969757
TI  - PCL-PGLA composite tubular scaffold preparation and biocompatibility
      investigation.
AB  - The objective of this paper was to fabricate a biodegradable tubular scaffold for
      small diameter (d<6 mm) blood vessel tissue engineering. The tube scaffold needed
      a porous wall for cell attachment, proliferation and tissue regeneration with its
      degradation. A novel method given in this paper was to coat a porous layer of
      poly (epsilon-caprolactone) (PCL) on the outside of a poly (glycolic-co-lactic
      acid) (PGLA with GA:LA=90:10) fiber braided tube to give a PCL-PGLA composite.
      The PGLA tube was fabricated using a braiding machine by inserting a Teflon tube
      with the desired diameter in center of the 20 spindles, which are the carriers of
      PGLA fibers. Changing the diameter of the Teflon tube can vary the inner diameter
      of a braided PGLA tube. Thermally induced phase separation method was used for
      PCL solution coating on the surface of the PGLA braided tube. Controlling the
      polymer concentration, non-solvent addition and quenching temperature generated
      the pore structures, with pore sizes ranging from 10-30 microm. The fibroblast
      cells were seeded on the tubular scaffold and cultured in vitro for the
      biocompatibility investigation. Histology results showed that the fibroblast
      cells proliferated on the interconnected pore of the PCL porous layer in 1 week.

PMID- 16969758
TI  - A case report of fracture of ceramic head in total hip arthroplasty: histological
      and biochemical features of perimplant tissues.
AB  - The authors analyzed the case of a patient with a non-cemented hip prosthesis
      with a ceramic-ceramic coupling. As a consequence of trauma the head fractured.
      Although the patient could feel the joint grinding, there was no pain and he
      continued daily living activities for nearly six months, which led to marked
      wearing of the ceramic head. SEM analysis with microprobe showed 'planed'
      surfaces on the ceramic head, suggesting repeated movements between the fractured
      components. Inside the cone of the head, signs of TiAlV, which is an alloy of the
      prosthetic stem, could be seen. Periprosthetic tissues were packed with ceramic
      wear particles of sizes ranging between 0.2 and 10 microns, according to the
      harvest site. Metal and mixed particles were also found. IL1, IL6, IL8 and IL10
      assays in the synovial liquid confirmed the inflammatory state and a modest
      induction of bone resorption, which was less than that observed in patients with
      loosened metal-polyethylene couplings. The humoral picture was compatible with
      the radiological aspect, which did not show marked signs of bone resorption. In
      revision surgery both ceramic components were replaced by a metal head and
      polyethylene liner. The clinical outcome after 12 months was very good.

PMID- 16969759
TI  - Evaluation of PDTC for removing Ni(II) from human serum transferrin in vitro.
AB  - Pyrrolidine dithiocarbamate (PDTC)can be an oral chelator with pKa=3.300+/-0.002.
      It behaves as a bidentate ligand at serum pH. The effect of pH on Ni2+-Tf
      indicated that the maximum adsorption was at pH=7.4. The effective Ni-PDTC
      binding constant was determined (logk=11.1+/-0.1) for the 1:2 Ni(PDTC)2 complex
      using UV-vis spectra. The isosbestic point at 298 indicated that the complexation
      reaction was done directly (without side reaction). Removal of Ni from
      transferrin (Tf) was investigated by reverse titration of PDTC at 25 masculineC
      and pH=7.4 using UV-vis spectra. PDTC is able to remove 25% of Ni from human
      serum transferrin.

PMID- 16969760
TI  - Use of the adjective 'membranous' to categorize hemodiafiltration and
      hemofiltration.

PMID- 16969761
TI  - BTKbase: the mutation database for X-linked agammaglobulinemia.
AB  - X-linked agammaglobulinemia (XLA) is a hereditary immunodeficiency caused by
      mutations in the gene encoding Bruton tyrosine kinase (BTK). XLA patients have a
      decreased number of mature B cells and a lack of all immunoglobulin isotypes,
      resulting in susceptibility to severe bacterial infections. XLA-causing mutations
      are collected in a mutation database (BTKbase), which is available at
      http://bioinf.uta.fi/BTKbase. For each patient the following information is given
      (when available): the identification of the entry, a plain English description of
      the mutation followed by a reference, formal characterization of the mutation,
      and the various parameters from the patient. BTKbase is implemented with the
      MUTbase program suite, which provides an easy, interactive, and quality
      controlled submission of information to mutation databases. BTKbase version 8
      lists mutation entries of 1,111 patients from 973 unrelated families showing 602
      unique molecular events. The localization of the mutations on the gene and
      protein for BTK can be analyzed by clicking sequences on the web pages. The
      distribution of the mutations in the five structural domains is approximately
      proportional to the length of the domains, except for the Tec homology (TH)
      domain. The most frequently affected sites are CpG dinucleotides. The majority of
      the missense mutations are structural-disturbing Bruton tyrosine kinase (Btk)
      folding or decreasing stability. Many of the mutations affect functionally
      significant, conserved residues. The structural consequences of the mutations in
      all the domains have been studied based on crystallographic and nuclear magnetic
      resonance (NMR) structures as well as computer-aided molecular modeling.

PMID- 16969762
TI  - A Bayesian approach on molecules and behavior: reconsidering phylogenetic and
      evolutionary patterns of the Salamandridae with emphasis on Triturus newts.
AB  - The monophyly of European newts of the genus Triturus within the family
      Salamandridae has for decades rested on presumably homologous behavioral and
      morphological characters. Molecular data challenge this hypothesis, but the
      phylogenetic position of Triturus within the Salamandridae has not yet been
      convincingly resolved. We addressed this issue and the temporal divergence of
      Triturus within the Salamandridae with novel Bayesian approaches applied to DNA
      sequence data from three mitochondrial genes (12S, 16S and cytb). We included 38
      salamandrid species comprising all 13 recognized species of Triturus and 16 out
      of 17 salamandrid genera. A clade comprising all the "Newts" can be separated
      from the "True Salamanders" and Salamandrina clades. Within the "Newts" well
      supported clades are: Tylototriton-Pleurodeles, the "New World Newts"
      (Notophthalmus-Taricha), and the "Modern Eurasian Newts" (Cynops, Pachytriton,
      Paramesotriton=together the "Modern Asian Newts", Calotriton, Euproctus,
      Neurergus and Triturus species). We found that Triturus is a non-monophyletic
      species assemblage, which includes four groups that are themselves monophyletic:
      (i) the "Large-Bodied Triturus" (six species), (ii) the "Small-Bodied Triturus"
      (five species), (iii) T. alpestris and (iv) T. vittatus. We estimated that the
      last common ancestor of Triturus existed around 64 million years ago (mya) while
      the root of the Salamandridae dates back to 95 mya. This was estimated using a
      fossil-based molecular dating approach and an explicit framework to select
      calibration points that least underestimated their corresponding nodes. Using the
      molecular phylogeny we mapped the evolution of life history and courtship traits
      in Triturus and found that several Triturus-specific courtship traits evolved
      independently.

PMID- 16969764
TI  - Synthesis and matrix-assisted laser desorption/ionization time-of-flight
      characterization of bisphenol-A copolyformals containing nickel(II)/Schiff base,
      eicosane and 2-butene units in the main chain.
AB  - Some bisphenol-A copolyformals, containing in the main chain different amounts of
      a Ni-diimine nonlinear optical (NLO)-chromophore, eicosane and/or 2-butene units,
      were synthesized by condensation reaction between dibromomethane and suitable
      mixtures of Ni(II)/Schiff base complex, 1,20-di(bisphenol-A)ether-eicosane and/or
      1,4-di(bisphenol-A)ether-2-butene. Structural composition and thermal properties
      of polymeric materials were inferred by analyses by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS), nuclear
      magnetic resonance (NMR), gel permeation chromatography (GPC), differential
      scanning calorimetry (DSC) and thermogravimetry (TG). MALDI-TOF data show that
      both Ni-diimine and unsaturated units are present in the copolyformals with a
      homogeneous arrangement in all the polymer mass range (GPC data). It has also
      been ascertained that the glass transition temperature (Tg) of the copolymers
      changes as a consequence of the abundance of aliphatic units in the
      macromolecules (DSC data). Cross-linking experiments of the copolymer at
      temperatures near the Tg value and under UV irradiation were also performed.

PMID- 16969763
TI  - Comprehensive survey of mutations in RP2 and RPGR in patients affected with
      distinct retinal dystrophies: genotype-phenotype correlations and impact on
      genetic counseling.
AB  - X-linked forms of retinitis pigmentosa (RP) (XLRP) account for 10 to 20% of
      families with RP and are mainly accounted for by mutations in the RP2 or RP
      GTPase regulator (RPGR) genes. We report the screening of these genes in a cohort
      of 127 French family comprising: 1) 93 familial cases of RP suggesting X-linked
      inheritance, including 48 out of 93 families with expression in females but no
      male to male transmission; 2) seven male sibships of RP; 3) 25 sporadic male
      cases of RP; and 4) two cone dystrophies (COD). A total of 5 out of the 93 RP
      families excluded linkage to the RP2 and RP3 loci and were removed form the
      cohort. A total of 14 RP2 mutations, 12 of which are novel, were identified in 14
      out of 88 familial cases of RP and 1 out of 25 sporadic male case (4%). In 13 out
      of 14 of the familial cases, no expression of the disease was noted in females,
      while in 1 out of 14 families one woman developed RP in the third decade. A total
      of 42 RPGR mutations, 26 of which were novel, were identified in 80 families,
      including: 69 out of 88 familial cases (78.4%); 2 out of 7 male sibship (28.6%);
      8 out of 25 sporadic male cases (32.0%); and 1 out of 2 COD. No expression of the
      disease was noted in females in 41 out of 69 familial cases (59.4%), while at
      least one severely affected woman was recognized in 28 out of 69 families
      (40.6%). The frequency of RP2 and RPGR mutations in familial cases of RP
      suggestive of X-linked transmission are in accordance to that reported elsewhere
      (RP2: 15.9% vs. 6-20%; RPGR: 78.4% vs. 55-90%). Interestingly, about 30% of male
      sporadic cases and 30% of male sibships of RP carried RP2 or RPGR mutations,
      confirming the pertinence of the genetic screening of XLRP genes in male patients
      affected with RP commencing in the first decade and leading to profound visual
      impairment before the age of 30 years.

PMID- 16969765
TI  - CreateTarget and Analyze This!: new software assisting imaging mass spectrometry
      on Bruker Reflex IV and Ultraflex II instruments.
AB  - Two new software programs are presented which enable matrix-assisted laser
      desorption/ionisation imaging mass spectrometry (MALDI-IMS) on Bruker Reflex and
      Ultraflex instruments. The first program, CreateTarget, creates a high density
      raster with the dimensions of the tissue section, and converts these parameters
      into a virtual target plate file that can be imported in the normal mass
      spectrometer control software. Following automated spectrum acquisition, the
      second program, Analyze This!, converts the array of spectra into an Analyze 7.5
      image format that can be read by image analysis software. These two tools are
      sufficient to allow IMS, and offer a valid alternative to commercially available
      software. CreateTarget and Analyze This! are available free of charge.

PMID- 16969766
TI  - High-performance liquid chromatography/atmospheric pressure chemical ionization
      tandem mass spectrometry determination of cholesterol uptake by Caco-2 cells.
AB  - A simple, sensitive and selective liquid chromatography/atmospheric pressure
      chemical ionization tandem mass spectrometric method (LC/APCI-MS/MS) was
      developed and applied to quantitative determination of uptake of cholesterol by
      Caco-2 human intestine cells. Caco-2 cells were cultured in medium containing
      cholesterol-3,4-13C2 and phytosterols from nutritional supplements after in vitro
      digestion. Cellular cholesterol (cholesterol-3,4-13C2) and endogenous cholesterol
      were extracted using methanol/chloroform (1:2, v/v) and directly analyzed using
      LC/APCI-MS/MS with selected reaction monitoring (SRM), using cholesterol
      2,2,3,4,4,6-d6 as an internal standard. Detection and quantification limits were
      2.2 and 7.2 pmol, respectively. This method provides an effective tool for rapid
      determination of cholesterol uptake by cells with increased selectivity and
      sensitivity in comparison to previously reported LC/APCI-MS analysis using
      selected ion monitoring (SIM).

PMID- 16969767
TI  - Simultaneous quantification of fexofenadine and pseudoephedrine in human plasma
      by liquid chromatography/tandem mass spectrometry with electrospray ionization:
      method development, validation and application to a clinical study.
AB  - To support the pharmacokinetic and bioavailability study of a once-daily
      fexofenadine/pseudoephedrine combination, a high-performance liquid
      chromatography/positive ion electrospray tandem mass spectrometry (HPLC/ESI
      MS/MS) method for the simultaneous quantification of fexofenadine and
      pseudoephedrine was developed and validated with 500 microL human plasma using
      mosapride as an internal standard (IS). Following solid-phase extraction, the
      analytes were separated using an isocratic mobile phase on a reversed-phase
      column and analyzed by MS/MS in the multiple reaction monitoring mode using the
      respective [M+H]+ ions, m/z 502/466 for fexofenadine, m/z 166/148 for
      pseuoephedrine and m/z 422/198 for the IS. The method exhibited linear dynamic
      ranges of 1-500 ng/mL and 2-1000 ng/mL for fexofenadine and pseudoephedrine,
      respectively, in human plasma. The lower limits of quantification were 1 and 2
      ng/mL with a relative standard deviation of less than 10% for fexofenadine and
      pseudoephedrine, respectively. Acceptable precision and accuracy were obtained
      for concentrations over the standard curve range. The total chromatographic run
      time was 2 min and more than 400 human plasma samples could be analyzed in one
      day by running the system overnight. The method is precise and sensitive enough
      for its intended purpose.

PMID- 16969768
TI  - Compound-specific stable carbon isotope ratios (delta13C values) of the
      halogenated natural product 2,3,3',4,4',5,5'-heptachloro-1'-methyl-1,2'-bipyrrole
      (Q1).
AB  - Compound-specific isotope analysis using gas chromatography interfaced to isotope
      ratio mass spectrometry (GC/IRMS) was applied for the determination of delta13C
      values of the marine halogenated natural product 2,3,3',4,4',5,5'-heptachloro-1'
      methyl-1,2'-bipyrrole (Q1). The delta13C value of a lab-made Q1 standard (-34.20
      +/- 0.27 per thousand) was depleted in 13C by more than 11 per thousand relative
      to the residues of Q1 in dolphin blubber from Australia and skua liver from
      Antarctica. This clarified that the synthesized Q1 was not the source for Q1 in
      the biota samples. However, two Australian marine mammals showed a large
      variation in the delta13C value, which, in our experience, was implausible. Since
      the GC/IRMS system was connected to a conventional ion trap mass spectrometer by
      a post-column splitter, we were able to closely inspect the peak purity of Q1 in
      the respective samples. While the mass spectra of Q1 did not indicate any
      impurity, a fronting peak of PCB 101 was identified in one sample. This
      interference falsified the delta13C value of the respective sample. Once this
      sample was excluded, we found that the delta13C values of the remaining samples,
      i.e. liver of Antarctic brown skua (-21.47 +/- 1.47 per thousand) and blubber of
      Australian melon-headed whale (-22.80 +/- 0.33 per thousand), were in the same
      order. The standard deviation for Q1 was larger in the skua samples than in the
      standard and the whale blubber sample. This was due to lower amounts of skua
      sample available. It remained unclear if the Q1 residues originate from the same
      producer and location.

PMID- 16969769
TI  - A study of the elimination of water from lithium-cationized tripeptide methyl
      esters by means of tandem mass spectrometry and isotope labeling.
AB  - Extensive isotope labeling (2H, 13C and 15N), collision-induced dissociation
      (CID) and multiple-stage tandem mass spectrometry were used to investigate the
      elimination of H2O from a series of model, metal-cationized tripeptide methyl
      esters. The present results corroborate our earlier suggestion that loss of water
      from lithiated peptides is initiated by a nucleophilic attack from the N-terminal
      side upon an amide carbonyl carbon atom to form a five-membered ring as an
      intermediate followed by 1,2-elimination of water. We show that the nucleophilic
      atom is the oxygen atom of the N-terminal amide group in the fragmentation of
      [AcGGGOMe+Li]+ as well as [GGGOMe+Li]+. However, the subsequent fragmentation is
      markedly different in the two cases as a result of the absence and presence of a
      free amino group. In particular, extensive scrambling of protons in the alpha
      positions of GGGOMe is observed, presumably as a consequence of intervention of
      the basic amino group.

PMID- 16969770
TI  - Protein profile of osteoarthritic human articular cartilage using tandem mass
      spectrometry.
AB  - Articular cartilage contains both chondrocyte cells and extracellular matrix
      (ECM) components. Currently, comprehensive information concerning the protein
      composition of human articular cartilage tissue is somewhat lacking. In this
      report we detail the use of tandem mass spectrometry (MS/MS) for a preliminary
      global identification of proteins from human articular knee cartilage tissue from
      patients diagnosed with osteoarthritis. Knee cartilage supernatant was
      fractionated using one-dimensional sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (1D-SDS-PAGE), in-gel digested and peptide sequences were then
      determined by performing on-line nano-liquid chromatography (LC)/MS/MS
      experiments using an ion trap mass spectrometer. Altogether, over 100 different
      proteins from nearly 700 unique peptide sequences were detected by MS/MS. The
      majority of the proteins identified are involved in ECM organization (35%),
      signal transduction and cell communication (14%), immune response (11%) and
      metabolism and energy pathways (11%). Proteins observed included several well
      known cartilage components as well as lower abundant lesser known ECM proteins.
      Possible degradation products in the cartilage sample, such as from cartilage
      link protein, could also be detected by our mass spectrometry methods. We show
      here that mass spectrometry can be utilized as a tool for a fast, accurate and
      sensitive analysis of a complex mixture of cartilage proteins. It is believed
      that this type of proteomic analysis will aid future work centered on
      investigating the pathology of this and other related joint diseases.

PMID- 16969771
TI  - A high-throughput, fully automated liquid/liquid extraction liquid
      chromatography/mass spectrometry method for the quantitation of a new
      investigational drug ABT-869 and its metabolite A-849529 in human plasma samples.
AB  - ABT-869 is a novel ATP-competitive inhibitor for all the vascular endothelial
      growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor tyrosine
      kinases (RTKs). It is one of the oncology drugs in development at Abbott
      Laboratories and has great potential for enhanced anti-tumor efficacy as well as
      activity in a broad range of human cancers. We report here an accurate, precise
      and rugged liquid chromatography/mass spectrometry (LC/MS/MS) assay for the
      quantitative measurement of ABT-869 and its acid metabolite A-849529. A fully
      automated 96-well liquid/liquid extraction method was achieved utilizing a
      Hamilton liquid handler. The only manual intervention required prior to LC/MS/MS
      injection is to transfer the 96-well plate to a drying rack to dry the extracts
      then transfer the plate back to the Hamilton for robotic reconstitution. The
      linear dynamic ranges were from 1.1 to 598.8 ng/mL for ABT-869 and from 1.1 to
      605.8 ng/mL for A-849529. The coefficient of determination (r2) for all analytes
      was greater than 0.9995. For the drug ABT-869, the intra-assay coefficient of
      variance (CV) was between 0.4% and 3.7% and the inter-assay CV was between 0.9%
      and 2.8%. The inter-assay mean accuracy, expressed as percent of theoretical, was
      between 96.8% and 102.2%. For the metabolite A-849529, the intra-assay CV was
      between 0.5% and 5.1% and the inter-assay CV was between 0.8% and 4.9%. The inter
      assay mean accuracy, expressed as percent of theoretical, was between 96.9% and
      100.6%.

PMID- 16969772
TI  - Sequence-dependent binding of dipeptides by an artificial receptor in water.
AB  - An artificial dipeptide receptor (1) was designed and observed to bind the
      deprotonated dipeptide Ac-D-Ala-D-Ala-OH in buffered water with K = 33,100 M(-1),
      whereas other dipeptides such as Ac-Gly-Gly-OH or Ac-D-Val-D-Val-OH were bound
      less efficiently, by factors of more than 10 (K < 3000 M(-1)). The efficient
      binding and the pronounced sequence selectivity are the result of a combination
      of strong electrostatic contacts and size-discriminating hydrophobic
      interactions. To provide such a combination, a guanidiniocarbonylpyrrole cation
      was attached to a novel cyclotribenzylene-substituted alanine derivative 5, to
      provide a hydrophobic bowl-shaped cavity just large enough to bind a methyl group
      but not any larger alkyl chains, thus causing the receptor to prefer alanine to
      valine. We describe the synthesis of 1 and the evaluation of its complexation
      properties in UV and fluorescence titration studies.

PMID- 16969773
TI  - Highly selective hydrogenation of carbon-carbon multiple bonds catalyzed by the
      cation [(C(6)Me(6))(2)Ru(2)(PPh(2))H(2)](+): molecular structure of
      [(C(6)Me(6))(2)Ru(2)(PPh(2))(CHCHPh)H](+), a possible intermediate in the case of
      phenylacetylene hydrogenation.
AB  - The dinuclear cation [(C(6)Me(6))(2)Ru(2)(PPh(2))H(2)](+) (1) has been studied as
      the catalyst for the hydrogenation of carbon-carbon double and triple bonds. In
      particular, [1][BF(4)] turned out to be a highly selective hydrogenation catalyst
      for olefin functions in molecules also containing reducible carbonyl functions,
      such as acrolein, carvone, and methyljasmonate. The hypothesis of molecular
      catalysis by dinuclear ruthenium complexes is supported by catalyst-poisoning
      experiments, the absence of an induction period in the kinetics of cyclohexene
      hydrogenation, and the isolation and single-crystal X-ray structure analysis of
      the tetrafluoroborate salt of the cation
      [(C(6)Me(6))(2)Ru(2)(PPh(2))(CHCHPh)H](+) (2), which can be considered as an
      intermediate in the case of phenylacetylene hydrogenation. On the basis of these
      findings, a catalytic cycle is proposed which implies that substrate
      hydrogenation takes place at the intact diruthenium backbone, with the two
      ruthenium atoms acting cooperatively in the hydrogen-transfer process.

PMID- 16969774
TI  - DyNAs: constitutional dynamic nucleic acid analogues.
AB  - Dynamic cationic polymers were generated in aqueous media from functionally
      complementary monomers bearing nucleobase groups. (1)H NMR spectroscopy was used
      to follow the polycondensation reaction of the nucleobase-appended dihydrazides 1
      and 2 with the dialdehydes B and C. The reversibility of these polymers was
      established by proton NMR spectroscopy through exchange of the dihydrazide 2 with
      polymer 1 B. The polymers 1 B, 2 B, 1 C, and 2 C represent dynamic biopolymers of
      nucleic acid type, DyNAs. Electrostatic interaction of these polymers with
      polyanionic entities, such as polyphosphates, polynucleotides, and polyaspartic
      acid, was shown to take place. It induces a change in size of the dynamic
      polymer, as it responds by an increase in degree of polymerization to an increase
      of the overall anionic charge introduced, that is, to the total electrostatic
      interaction.

PMID- 16969776
TI  - (NHC)Copper(I)-catalyzed [3+2] cycloaddition of azides and mono- or disubstituted
      alkynes.
AB  - A versatile and highly efficient catalyst for the Huisgen cycloaddition reaction
      has been developed. Previously isolated or in situ generated azides yielded 1,2,3
      triazoles with differently substituted alkynes in the presence of a [(NHC)CuBr]
      complex (NHC = N-heterocyclic carbene). Extremely high reaction rates and
      excellent yields were obtained in all cases. This catalytic system fulfils the
      requirements of "click chemistry" with its mild and convenient conditions,
      notably in water or solvent free reactions and simple isolation with no
      purification step. Furthermore, for the first time, an internal alkyne was
      successfully used in this copper-catalyzed cycloaddition reaction. DFT
      calculations on this particular system allowed for the proposition of a new
      mechanistic pathway for disubstituted alkynes.

PMID- 16969777
TI  - Tailor-made ligands for biocompatible nanoparticles.

PMID- 16969778
TI  - Calixarenes as hosts for ammonium cations: a quantum chemical study and mass
      spectrometric investigations.
AB  - Host-guest complexes of tetramethylcavitand with different ammonium cations were
      investigated by using a quantum chemical method at the density functional level
      (BP86, B3 LYP). The NH4+ cation is strongly bound to the host. Increasing methyl
      substitution at the cation decreases its inclination towards the complex
      formation. The calculated data are in line with results from electrospray
      ionization mass spectrometry (ESI-MS) experiments. They reveal stable aggregates
      only for the NH4+ cation and for the primary alkylammonium cations.

PMID- 16969779
TI  - Three-dimensional six-connecting organic building blocks based on
      polychlorotriphenylmethyl units--synthesis, self-assembly, and magnetic
      properties.
AB  - The synthesis of a three-dimensional, six-connecting, organic building block
      based on a robust, rigid, and open-shell polychlorotriphenylmethyl (PTM) unit
      (radical 1) is reported, and its self-assembly properties are described in
      detail. The tendencies of this highly polar molecule and its hydrogenated
      precursor, compound 4, to form hydrogen bonds with oxygenated solvents ([1THF(6)]
      and [4THF(6)]) were reduced by replacing THF with diethyl ether in the
      crystallization process to yield two-dimensional (2D) hydrogen-bonded structures
      ([1(Et(2)O)(3)] and [4(Et(2)O)(3)]). The presence of direct hydrogen bonds
      between the radicals in the latter phase of 1 gives rise to very weak
      ferromagnetic intermolecular interactions at low temperatures, whereas when the
      radicals are isolated by THF molecules these interactions are antiferromagnetic
      and very weak. The role played by the carboxylic groups not only in the self
      assembly properties but also in the transmission of the magnetic interactions has
      been illustrated by determination of the crystal structure and measurement of the
      magnetic properties of the corresponding hexaester radical 6, in which the close
      packing of molecular units gives rise to weak antiferromagnetic intermolecular
      interactions. Attempts to avoid solvation of the molecules in the solid state and
      to increase the structural and magnetic dimensionality were pursued by
      recrystallization of both compounds 1 and 4 from concentrated nitric acid,
      affording two three-dimensional (3D) robust hydrogen-bonded structures. While the
      structure obtained with compound 4 is characterized by the presence of polar
      channels and boxes containing water guest molecules along the c axis, radical 1
      was oxidized to the corresponding fuchsone 10, which presented a completely
      different close-packed, guest-free structure.

PMID- 16969780
TI  - Nickel(II) complexes of bidentate N-heterocyclic carbene/phosphine ligands:
      efficient catalysts for Suzuki coupling of aryl chlorides.
AB  - Nickel(II) complexes of bidentate N-heterocyclic carbene (NHC)/phosphane ligand L
      were prepared and structurally characterized. Unlike palladium, which forms
      [PdCl(2)(L)], the stable nickel product isolated is the ionic [Ni(L)(2)]Cl(2).
      These Ni(II) complexes are highly robust in air. Among different N-substituents
      on the ligand framework, the nickel complex of ligand L bearing N-1
      naphthylmethyl groups (2 a) is a highly effective catalyst for Suzuki cross
      coupling between phenylboronic acid and a range of aryl halides, including
      unreactive aryl chlorides. The activities of 2 a are largely superior to those of
      other reported nickel NHC complexes and their palladium counterparts. Unlike the
      previously reported [NiCl(2)(dppe)] (dppe=1,2-bis(diphenylphosphino)ethane), 2 a
      can effectively catalyze the cross-coupling reaction without the need for a
      catalytic amount of PPh(3), and this suggests that the PPh(2) functionality of
      hybrid NHC ligand L can partially take on the role of free PPh(3). However, for
      unreactive aryl chlorides at low catalyst loading, the presence of PPh(3)
      accelerates the reaction.

PMID- 16969781
TI  - Comment on the comparative use of the electron density and its Laplacian.

PMID- 16969782
TI  - A new protein engineering approach combining chemistry and biology, part I; site
      specific incorporation of 4-iodo-L-phenylalanine in vitro by using misacylated
      suppressor tRNAPhe.
AB  - An Escherichia coli suppressor tRNA(Phe) (tRNA(Phe) (CUA)) was misacylated with 4
      iodo-L-phenylalanine by using the A294G phenylalanyl-tRNA synthetase mutant (G294
      PheRS) from E. coli at a high magnesium-ion concentration. The preacylated tRNA
      was added to an E. coli cell-free system and a Ras protein that contained the 4
      iodo-L-phenylalanine residue at a specific target position was synthesized. Site
      specific incorporation of 4-iodo-L-phenylalanine was confirmed by using LC-MS/MS.
      Free tRNA(Phe) (CUA) was not aminoacylated by aminoacyl-tRNA synthetases (aaRSs)
      present in the E. coli cell-free system. Our approach will find wide application
      in protein engineering since an aryl iodide tag on proteins can be used for site
      specific functionalization of proteins.

PMID- 16969783
TI  - An unusual variant of the biceps brachii.

PMID- 16969784
TI  - Tongue teratoma--a rare form of fetal extragonadal teratoma diagnosed at 30
      weeks' gestation.

PMID- 16969785
TI  - Timely diagnosis of twin-to-twin transfusion syndrome in monochorionic twin
      pregnancies by biweekly sonography combined with patient instruction to report
      onset of symptoms.
AB  - OBJECTIVES: To assess the value of serial ultrasound examinations together with
      patient instructions to report the onset of symptoms in achieving timely
      detection of twin-to-twin transfusion syndrome (TTTS) in a cohort of
      monochorionic diamniotic twin pregnancies, and to evaluate sonographic TTTS
      predictors. METHODS: Timely detection of TTTS was defined as diagnosis before
      severe complications of TTTS occurred, such as preterm prelabor rupture of
      membranes, very preterm delivery (24-32 weeks of pregnancy), fetal hydrops, or
      intrauterine fetal death. During a 2-year period, a prospective series of 23
      monochorionic twin pregnancies was monitored from the first trimester until
      delivery. At least every 2 weeks we performed ultrasound and Doppler measurements
      (nuchal translucency thickness, presence of membrane folding, estimated fetal
      weight, deepest vertical pocket, bladder filling, and Doppler waveforms of the
      umbilical artery, ductus venosus and umbilical vein). Measurements of TTTS cases
      were compared with those of non-TTTS cases matched for gestational age.
      Furthermore, patients were informed about the symptoms caused by TTTS, and
      instructed to consult us immediately in case of rapidly increasing abdominal size
      or premature contractions. RESULTS: In all four TTTS cases, the diagnosis was
      timely. At the time of diagnosis, one case was at Quintero Stage 1, two at
      Quintero Stage 2, and one at Quintero Stage 3. Two of the TTTS cases became
      apparent after the patients' feeling of rapidly increasing girth. The
      identification of TTTS predictors was successful with respect to one parameter:
      isolated polyhydramnios in one sac, without oligohydramnios in the other,
      preceded the ultimate diagnosis of TTTS in two of the four TTTS cases. All other
      ultrasound measurements of TTTS cases, prior to the diagnosis of TTTS, were
      within the range of measurements of non-TTTS cases. CONCLUSION: Biweekly
      ultrasound examinations, with special attention to the amniotic fluid
      compartments of both fetuses, combined with detailed patient instructions to
      report the onset of symptoms resulted in timely diagnosis of all TTTS cases and
      appears to be a safe program for monitoring monochorionic twin pregnancies.

PMID- 16969786
TI  - Effect of umbilical ring constriction on Wharton's jelly.
AB  - OBJECTIVE: The turgor of Wharton's jelly depends on osmotic and hydrostatic
      pressures. We tested the hypothesis that umbilical ring constriction has an
      impact on umbilical venous hemodynamics and thus on the volume of Wharton's
      jelly. METHODS: In a cross-sectional study of 237 low-risk singleton pregnancies,
      the cross-sectional area of the fetal end of the umbilical cord was determined
      using sonography at 20-41 weeks of gestation. The inner area of the two arteries
      and the vein was also measured and subtracted from the cord area to calculate the
      area of Wharton's jelly. Based on the Bernoulli equation, the degree of vein
      constriction at the umbilical ring was assessed using the blood velocity
      increment at the abdominal inlet. Regression analysis and SD-score statistics
      were used to construct mean values and to assess the effects. The dataset was
      also analyzed for gender-specific effects. RESULTS: The umbilical cord cross
      sectional area increased with gestational age during the period 20-31 weeks,
      remaining essentially stable thereafter. The Wharton's jelly increased with
      gestational age from 20 until 31-32 weeks of gestation and remained at the same
      level for the rest of the pregnancy. At mid-gestation, on average 70% of the cord
      cross-sectional area was occupied by Wharton's jelly; at 31 weeks and later this
      value was 60%. Umbilical vein constriction was associated with reduced umbilical
      cord cross-sectional area and Wharton's jelly in female fetuses (P = 0.0007 and P
      = 0.003, respectively), but not in male fetuses. CONCLUSIONS: Under physiological
      conditions, umbilical ring constriction affects umbilical vein hemodynamics, with
      corresponding effects on the umbilical cord cross-sectional area and the amount
      of Wharton's jelly. Interestingly, the effects are gender-specific.

PMID- 16969787
TI  - An fMRI study of somatosensory-implicated acupuncture points in stable
      somatosensory stroke patients.
AB  - PURPOSE: To assess differences in brain responses between stroke patients and
      controls to tactile and electrical acupuncture stimulation using functional MRI
      (fMRI). MATERIALS AND METHODS: A total of 12 male, clinically stable stroke
      patients with left side somatosensory deficits, and 12 age-matched male control
      subjects were studied. fMRI was performed with two different paradigms; namely,
      tactile stimuli and electrical stimulation at acupuncture points LI4 and LI11 on
      the affected side of the body. fMRI data were analyzed using SPM99. RESULTS:
      Tactile stimulation in both patients and controls produced significant activation
      in primary and secondary sensory and motor cortical areas and cerebellum. Greater
      activation was present in patients than controls in the somatosensory cortex with
      both the tactile task and the acupuncture point (acupoint) stimulation.
      Activation was greater during the tactile task than the acupuncture stimulation
      in patients and normal controls. CONCLUSION: Differences observed between
      patients and controls on both tasks may indicate compensatory over recruitment of
      neocortical areas involved in somatosensory perception in the stroke patients.
      The observed differences between patients and controls on the acupoint
      stimulation task may also indicate that stimulation of acupoints used
      therapeutically to enhance recovery from stroke, selectively activates areas
      thought to be involved in mediating recovery from stroke via functional
      plasticity. fMRI of acupoint stimulation may illustrate the functional substrate
      of the therapeutically beneficial effect of acupuncture in stroke rehabilitation.

PMID- 16969788
TI  - Delayed hyperenhancement patterns in occlusive and reperfused myocardial infarcts
      during different healing stages.
AB  - PURPOSE: To investigate delayed hyperenhancement during different healing stages
      of myocardial infarct with and without reperfusion in a pig model. MATERIALS AND
      METHODS: Twelve pigs were studied. Six pigs were subjected to permanent right
      coronary artery (RCA) occlusion, and the other six were subjected to transient 90
      minute RCA occlusion. In vivo MRI including first-pass perfusion and myocardial
      delayed enhancement (MDE) was performed at four, eight, 12, and 24 hours, and
      eight days after the artery occlusion. The MDE scan was repeated four times, two
      to 32 minutes after contrast administration. RESULTS: For all six pigs without
      reperfusion, the four-hour MRI showed transmural perfusion defect and no delayed
      hyperenhancement; from eight hours on, delayed hyperenhancement appeared and its
      spatial extent gradually increased until it became transmural hyperenhancement at
      eight days. However, in all six pigs with reperfusion, hyperenhancement was
      present at every stage from four hours to eight days. Pathology confirmed the
      existence of infarct at various stages of healing irrespective of reperfusion
      status. CONCLUSION: Occlusive hyperacute infarct did not exhibit any delayed
      hyperenhancement, which indicates that perfusion plays an important role in
      delayed enhancement at the hyperacute stage.

PMID- 16969790
TI  - Imaging living mice using a 1-T compact MRI system.
AB  - PURPOSE: To determine the feasibility of imaging living mice with a 1-T compact
      MRI system and investigate appropriate imaging techniques for use in routine
      animal experiments. MATERIALS AND METHODS: An MRI system consisting of a 1-T
      permanent magnet and compact console was used. Images of the entire trunks of
      living mice were obtained on the system using a T1-weighted three-dimensional
      fast low-angle shot (3D FLASH) sequence, and image quality was evaluated in
      relation to imaging techniques. RESULTS: Restraint of respiratory motion improved
      the image quality. Decreasing the slice thickness reduced artificial
      inhomogeneity in signal intensity (SI). Substantial effects of TR and FA on image
      quality were also demonstrated. With the determined techniques, images covering
      the entire trunk with a voxel size of 0.26x0.26x0.52 mm were acquired in an
      acquisition time of five minutes 28 seconds and a total experiment time of <20
      minutes, and various organs and subcutaneous tumors were clearly visualized.
      CONCLUSION: The compact MRI system provides images of living mice with acceptable
      quality in a reasonable time. Considering its convenience, it appears to be
      suitable for use in routine mouse experiments.

PMID- 16969789
TI  - Spontaneous detorsion of the ovary: can it be diagnosed by MRI?
AB  - PURPOSE: To determine whether recent progress in imaging has made it possible to
      diagnose spontaneous detorsion, which is an accepted concept in the gynecological
      literature but until now has been a presumptive diagnosis that could not be
      confirmed because of the lack of imaging proof. MATERIALS AND METHODS: We
      searched for patients who had a diagnosis of spontaneous detorsion on MRI between
      January 2000 and January 2003, and selected only patients who met a selection of
      strict criteria, including mainly enlargement and hyperintensity of ovarian
      stroma on T2-weighted (T2W) images, clinical findings compatible with torsion and
      detorsion, and return of the stroma to normal size on follow-up examinations.
      Other signs of torsion, such as tubal thickening, were appreciated but not
      mandatory. Clinical follow-up for at least three years was available. RESULTS:
      Four patients met the study criteria. No stabilizing procedure was performed in
      the ovaries. One patient recurred and lost her ovary. CONCLUSION: The diagnosis
      of torsion followed by spontaneous detorsion was made with high probability in a
      selected number of patients. The clinical management of such patients remains a
      matter of debate. Laparoscopy with oophoropexy would be useful for young patients
      in whom close follow-up cannot be achieved.

PMID- 16969791
TI  - Cine flow measurements using phase contrast with undersampled projections: in
      vitro validation and preliminary results in vivo.
AB  - PURPOSE: To assess the accuracy of flow measurements in vitro and in vivo during
      scan times shorter than a breath-hold using a 2D cine phase contrast (PC)
      undersampled radial acquisition method, which may be useful for measuring flow,
      especially in vessels subject to motion during respiration. MATERIALS AND
      METHODS: For in vitro assessment, a flow phantom was imaged at various flow rates
      and undersampling factors. For in vivo assessment, five normal subjects were
      imaged and the flow rate in the aorta was compared with the sum of the flow rates
      in the iliac arteries. RESULTS: For results in vitro, the accuracy of flow
      measurements was maintained with scan times as low as 13-17 seconds. For results
      in vivo, scans acquired in less than 25 seconds provided flow measurements in the
      aorta that corresponded well to the sum of flow measurements in the iliac
      arteries. CONCLUSION: The undersampled radial acquisition cine PC technique
      provided accurate flow measurements in a flow phantom and in healthy human
      volunteers in scan times shorter than a typical breath-hold.

PMID- 16969792
TI  - T1- and T2-weighted fast spin-echo imaging of the brachial plexus and cervical
      spine with IDEAL water-fat separation.
AB  - PURPOSE: To compare the iterative decomposition of water and fat with echo
      asymmetry and least-squares estimation (IDEAL) method with fat-saturated T1
      weighted (T1W) and T2W fast spin-echo (FSE) and short-TI inversion recovery
      (STIR) imaging of the brachial plexus and cervical spine. MATERIALS AND METHODS:
      Images acquired at 1.5T in five volunteers using fat-saturated T1W and T2W FSE
      imaging and STIR were compared with T1W and T2W IDEAL-FSE images. Examples of T1W
      and T2W IDEAL-FSE images acquired in patients are also shown. RESULTS: T1W and
      T2W IDEAL-FSE demonstrated superior fat suppression (P<0.05) and image quality
      (P<0.05), compared to T1W and T2W fat-saturated FSE, respectively. SNR
      performance of T1W-IDEAL-FSE was similar to T1W FSE in the spinal cord (P=0.250)
      and paraspinous muscles (P=0.78), while T2W IDEAL-FSE had superior SNR in muscle
      (P=0.02) and CSF (P=0.02), and marginally higher cord SNR (P=0.09). Compared to
      STIR, T2W IDEAL-FSE demonstrated superior image quality (P<0.05), comparable fat
      suppression (excellent, P=1.0), and higher SNR performance (P<0.001). CONCLUSION:
      IDEAL-FSE is a promising method for T1W and T2W imaging of the brachial plexus
      and cervical spine.

PMID- 16969793
TI  - Automated perfusion-weighted MRI using localized arterial input functions.
AB  - PURPOSE: To investigate the utility of an automated perfusion-weighted MRI (PWI)
      method for estimating cerebral blood flow (CBF) based on localized arterial input
      functions (AIFs) as compared to the standard method of manual global AIF
      selection, which is prone to deconvolution errors due to the effects of delay and
      dispersion of the contrast bolus. MATERIALS AND METHODS: Analysis was performed
      on spin- and gradient-echo EPI images from 36 stroke patients. A local AIF
      algorithm created an AIF for every voxel in the brain by searching out voxels
      with the lowest delay and dispersion, and then interpolating and spatially
      smoothing them for continuity. A generalized linear model (GLM) for predicting
      tissue outcome, and MTT lesion volumes were used to quantify the performance of
      the localized AIF method in comparison with global methods using ipsilateral and
      contralateral AIFs. RESULTS: The algorithm found local AIFs in each case without
      error and generated a higher area under the receiver operating characteristic
      (ROC) curve compared to both global-AIF methods. Similarly, the local MTT lesion
      volumes had the least mean squared error (MSE). CONCLUSION: Automated CBF
      calculation using local AIFs is feasible and appears to produce more useful CBF
      maps.

PMID- 16969794
TI  - Increasing the luminescence of lanthanide complexes.
AB  - This review compares the chemical and physical properties of lanthanide ion
      complexes and of other narrow-emitting species that can be used as labels for
      cytometry. A series of luminescent lanthanide ion macrocyclic complexes, Quantum
      Dyes, which do not release or exchange their central lanthanide ion, do accept
      energy transfer from ligands, and are capable of covalent binding to
      macromolecules, including proteins and nucleic acids, is described and their
      properties are discussed. Two methods are described for increasing the
      luminescence intensity of lanthanide ion complexes, which intrinsically is not as
      high as that of standard fluorophores or quantum dots. One method consists of
      adding a complex of a second lanthanide ion in a micellar solution
      (columinescence); the other method produces dry preparations by evaporation of a
      homogeneous solution containing an added complex of a second lanthanide ion or an
      excess of an unbound antenna ligand. Both methods involve the Resonance Energy
      Transfer Enhanced Luminescence, RETEL, effect as the mechanism for the
      luminescence enhancement.

PMID- 16969795
TI  - An automatic procedure for evaluation of single cell motility.
AB  - BACKGROUND: Cell motility is vital in many physiological and pathological
      processes, such as embryogenesis, inflammation, wound healing, and metastasis.
      However, the time-consuming step in the evaluation of individual cell motility is
      the analysis of hundreds of recorded images of cell cultures in general
      consisting of retrieving images, one at a time, and marking the positions of
      individual cells by a computer mouse. Therefore, the aim of the present study was
      to develop a novel automatic procedure for the evaluation of cell motility.
      MATERIALS AND METHODS: The procedure was tested on fibroblasts and glioma and
      adenocarcinoma cells engineered to express the green fluorescent protein by
      either transient transfection or adenovirus transduction, allowing automatic
      recognition of cell coordinates on retrieved images. RESULTS: The effects of
      serum growth factors, teratogenic compounds, and overexpression of transcription
      factors on the motile behavior of cultured cells were determined. Cell motility
      was estimated by both manual and automatic marking of cell position and
      subsequently motility parameters were computed. The results obtained by the two
      procedures were found to correlate significantly. CONCLUSIONS: We developed a
      procedure allowing automatic video recording of sparsely seeded cells transfected
      with a plasmid or tranduced with a recombinant virus expressing the enhanced
      green fluorescent protein (EGFP).

PMID- 16969796
TI  - DNA methylation in stingless bees with low and high heterochromatin contents as
      assessed by restriction enzyme digestion and image analysis.
AB  - BACKGROUND: The stingless bee genus Melipona has been divided into two groups,
      based on their heterochromatin content. Melipona quadrifasciata and Melipona
      rufiventris have low and high levels of heterochromatin, respectively. Since
      condensed chromatin may be rich in methylated DNA sequences, M. quadrifasciata
      and M. rufiventris nuclei may contain different amounts of methylated CpG. These
      differences could be assessed by comparing Feulgen-DNA values obtained by image
      analysis of cells treated with the restriction enzymes Msp I and Hpa II that
      distinguish between methylated and unmethylated DNA. Msp I and Hpa II cleave the
      sequence -CCGG-, but there is no cleavage by Hpa II if the cytosine of the
      central CG dinucleotide is methylated. METHODS: Malpighian tubules of M.
      quadrifasciata and M. rufiventris were treated with Msp I and Hpa II prior to the
      Feulgen reaction, and analyzed by automatic scanning microspectrophotometry.
      RESULTS: The Feulgen-DNA values for the heterochromatin of M. rufiventris and for
      the small heterochromatin and some euchromatin domains of M. quadrifasciata
      mostly decreased after treatment with Msp I, but were unchanged after treatment
      with Hpa II. CONCLUSION: CpG methylation, although detected in diverse chromatin
      compartments in different bee species, may induce silencing effects required for
      the same cell physiology.

PMID- 16969797
TI  - Implementation of the EGFP-K562 flow cytometric NK test: determination of NK
      cytotoxic activity in healthy elderly volunteers before and after feeding.
AB  - BACKGROUND: Natural Killer (NK) cells are key actors of innate immunity that
      supervise the organism's cells, and fight against viral infections and cancer
      development through their cytotoxic activity. This cytotoxic activity is
      modulated by cytokines and hormones and could be influenced by physiological or
      pathological conditions. New techniques for measuring NK cytotoxic activity by
      flow-cytometry have recently been developed, and they correlated strongly with
      the standard chromium ((51)Cr) release assay. Our aim was to implement a
      previously published enhanced green fluorescent protein (EGFP)-K562 flow
      cytometric method and use it to evaluate NK cytotoxic activity under different
      nutritional conditions. METHODS: NK effector cells were isolated from peripheral
      blood mononuclear cells, and a K562 cell line stably transfected by EGFP was used
      as target cells. Different analytical parameters, including cell ratios and
      incubation times, were studied to improve the EGFP-K562 flow cytometric NK test
      conditions. RESULTS: The optimized test was then used to determine the effect of
      fasting and refeeding on NK cell numbers and activity in a physiological
      situation. NK cytotoxic activity in fasted conditions (30.4 +/- 4.4%) increased
      by a factor 1.7 +/- 0.2 (P = 0.0025) in nourished conditions (45.0 +/- 4.6%) in
      healthy elderly people. CONCLUSION: Therefore, this method provides a reliable,
      reproducible and rapid test for analyzing NK cytotoxicity under various
      conditions.

PMID- 16969798
TI  - Aged mice exhibit distinct peripheral B-cell phenotypes differing in apoptotic
      susceptibility: an ex vivo analysis.
AB  - BACKGROUND: Age-related changes in the antibody response have been classically
      associated with alterations in T-cell help, but increasing evidence shows that
      intrinsic B-cell defects exist. This article analyzes the apoptotic
      susceptibility of peripheral B-cells in aged and young control mice. MATERIALS
      AND METHODS: Freshly isolated lymphocytes from spleen and Peyer's patches (PPs)
      were labeled for B-cell lineage (B220(+) cells) and germinal center B subset
      (GCs, B220(+)/PNA(+) cells). Alternatively, splenic B-cells purified by MACS were
      used. Apoptosis was monitored by the Annexin V binding, incorporation of 3,3(')
      dihexyloxacarbocyanine iodide (DiOC(6)(3)), propidium iodide (PI) staining, and
      morphological changes. Moreover, intracellular Bcl-2 expression and Bad
      phosphorylation status were also analyzed in B-cells. RESULTS: We showed in aging
      mice an enhanced Annexin V(+)/PI(-) cell percentage in splenic B-lymphocytes,
      which was correlated with a lower DeltaPsi(m). By contrast, no change in
      apoptosis was observed in compartments known to be enriched in activated B-cells
      (GCs and PPs). Analysis of Bcl-2 levels revealed no modification. When using B
      cells purified by MACS, we strongly confirm data obtained on staining cells.
      Moreover, enhanced spontaneous apoptosis of splenic B-cells in aged mice was
      found to be correlated with a reduced phosphorylated Bad expression. CONCLUSION:
      Increased apoptosis of resting B-cells in old mice may be determined by an
      altered Bad phosphorylation, which in turn contributes to cell death by lowering
      the mitochondrial threshold for apoptosis.

PMID- 16969799
TI  - Syringe pumped high speed flow cytometry of oceanic phytoplankton.
AB  - BACKGROUND: Nanophytoplankton (2-20 microm) are less numerous than
      picophytoplankton (<2 microm) in the oceans but their biomass and production are
      comparable and sometimes higher. The accuracy of cytometry-based enumeration of
      phytoplankton ultimately depends on cell abundance and sample flow rate.
      Commercial flow cytometers in which sheath and core streams are driven by air
      pressure cannot produce sufficiently high, stable sample flow rate. The present
      study demonstrates the applicability of a syringe pump for flow cytometric
      enumeration of oceanic nanophytoplankton on two meridional transects across the
      Atlantic Ocean. METHODS: Commercially available syringe pumps were used to
      deliver live phytoplankton samples into a flow cell of standard flow cytometers
      (FACSort, FACSCalibur, BD) with increased flow rate of > 1.0 ml min(-) (1)
      compared to the normal air pressure sample delivery of < 0.1 ml min(-) (1). An
      auxiliary application of syringe pump flow cytometry for calibrating 0.5 microm
      bead concentration standards is also discussed. RESULTS: The results demonstrated
      that flow cytometry of samples injected at rates above 0.1 ml min(-) (1) is
      achievable and worthwhile. Counts of phytoplankton in air and syringe pumped
      samples agreed closely. Syringe pumping of samples offered a broader range of
      flow rates up to 0.8-1.0 ml min(-) (1) without detrimental effect on flow
      cytometric enumeration of cells. The increased number of coincidences at high
      flow rates led to an approximate 10% decrease of Cyanobacteria counts when the
      acquisition rate approached 1,000 particles s(-) (1), but seemed to have a lesser
      effect on counting rarer phytoplankton. The syringe pump flow cytometry allowed
      enumeration of phytoplankton groups at concentrations of 5-100 cells ml(-) (1),
      cell concentrations equivalent to those of Cyanobacteria in the twilight deep
      ocean. CONCLUSION: The proposed syringe pump modification of a FACS instrument
      represents a significant improvement for accurate enumeration of the less
      abundant phytoplankton and so gives better estimations of phytoplankton
      distribution and standing stocks.

PMID- 16969800
TI  - Factors affecting flow karyotype resolution.
AB  - BACKGROUND: One of the major factors which influences the chromosome purity
      achievable particularly during high speed sorting is the analytical resolution of
      individual chromosome peaks in the flow karyotype, as well as the amount of
      debris and fragmented chromosomes. We have investigated the factors involved in
      the preparation of chromosome suspensions that influence karyotype resolution.
      METHODS: Chromosomes were isolated from various human and animal cell types using
      a series of polyamine buffer isolation protocols modified with respect to pH,
      salt concentration, and chromosome staining time. Each preparation was analyzed
      on a MoFlo sorter (DAKO) configured for high speed sorting and the resolution of
      the flow karyotypes compared. RESULTS: High resolution flow cytometric data was
      obtained with chromosomes optimally isolated using hypotonic solution buffered at
      pH 8.0 and polyamine isolation buffer (with NaCl excluded) between pH 7.50 and
      8.0. Extending staining time to more than 8 h with chromosome suspensions
      isolated from cell lines subjected to sufficient metaphase arrest times gave the
      best result with the lowest percentage of debris generated, tighter chromosome
      peaks with overall lower coefficients of variation, and a 1- to 5-fold increase
      in the yield of isolated chromosomes. CONCLUSIONS: Optimization of buffer pH and
      the length of staining improved karyotype resolution particularly for larger
      chromosomes and reduced the presence of chromosome fragments (debris). However,
      the most interesting and surprising finding was that the exclusion of NaCl in PAB
      buffer improved the yield and resolution of larger chromosomes.

PMID- 16969801
TI  - Confocal spectral imaging in tissue with contrast provided by Raman vibrational
      signatures.
AB  - Confocal Raman imaging of biological materials offers the opportunity to extract
      chemical information on histologically defined regions and on sub-cellular
      organelles. This article reviews the technology and some successful applications.
      The chemical contrast from vibrational Raman spectroscopy is derived from the
      specific atomic motion of every molecule as detected by the Raman phenomenon.
      Examples show the successful identification of foreign material in pathological
      specimens, identification of lipid-type and calcium mineral-type in a mouse model
      of atherosclerosis, and component mapping in a pharmaceutical tablet. It is
      suggested that these methods can even be useful in studying metabolic disorders.

PMID- 16969802
TI  - Multispectral imaging of ion transport in neutral carrier-based cation-selective
      membranes.
AB  - BACKGROUND: High-resolution spectroscopic imaging of the cross section of ion
      selective membranes during real-time electrochemical measurements is termed
      spectroelectrochemical microscopy (SpECM). SpECM is aimed for optimizing the
      experimental conditions in mass transport controlled ion-selective electrode
      (ISE) membranes for improved detection limit. METHODS: The SpECM measurements are
      performed in a thin layer electrochemical cell. The key element of the cell is a
      membrane strip spacer ring assembly which forms a two compartment electrochemical
      cell. The cell is placed onto the stage of a microscope and the membrane strip is
      positioned in the center of the field of view. A slice of the image is focused
      onto the entrance slit of the imaging spectrometer. RESULTS: SpECM has been used
      for the determination of the diffusion coefficients of different membrane
      ingredients and for the quantitative assessment of the charged site
      concentrations in ISE membranes and membrane plasticizers. In addition, changes
      in the concentration profiles of the ionophore (free and complexed) and charged
      mobile sites inside the ISE membranes are documented upon the application of
      large external voltages. CONCLUSIONS: This account demonstrates the power and
      advantages of SpECM, a multispectral imaging method for investigations of mass
      transport processes in ISE membranes during electrochemical measurements.

PMID- 16969803
TI  - Single particle high resolution spectral analysis flow cytometry.
AB  - BACKGROUND: While conventional multiparameter flow cytometers have proven highly
      successful, there are several types of analytical measurements that would benefit
      from a more comprehensive and flexible approach to spectral analysis including,
      but certainly not limited to spectral deconvolution of overlapping emission
      spectra, fluorescence resonance energy transfer measurements, metachromic dye
      analysis, free versus bound dye resolution, and Raman spectroscopy. METHODS: Our
      system utilizes a diffraction grating to disperse the collected fluorescence and
      side-scattered light from cells or microspheres passing through the interrogation
      region over a rectangular charge-coupled-device image sensor. The flow cell and
      collection optics are taken from a conventional flow cytometer with minimal
      modifications to assure modularity of the system. RESULTS: Calibration of the
      prototype spectral analysis flow cytometer included wavelength characterization
      and calibration of the dispersive optics. Benchmarking of the system demonstrated
      a single particle/cell intensity sensitivity of 2160 MESF of R-Phycoerythrin.
      Single particle spectra taken with our instrument were validated against bulk
      solution fluorimeter and conventional flow cytometer measurements. Coefficients
      of variation of integrated spectral fluorescence intensity of several sets of
      standard fluorescent microspheres ranged from 1.4 to 4.8% on the spectral system.
      Spectral discrimination of free versus PI bound to cells is also demonstrated.
      CONCLUSIONS: It is demonstrated that the flow spectrometer has sufficient
      sensitivity and wavelength resolution to detect single cells and microspheres,
      including multi-fluorophore labeled microspheres. The capability to use both
      standard mathematical deconvolution techniques for data analysis, coupled with
      the feasibility of integration with existing flow cytometers, will improve the
      accuracy and precision of ratiometric measurements, enable the analysis of more
      discrete emission bands within a given wavelength range, and allow more precise
      resolution of the relative contribution of individual fluorophores in multiply
      tagged samples, thereby enabling a range of new applications involving the
      spectral analysis of single cells and particles.

PMID- 16969804
TI  - Confocal laser scanning microscopy of whole mouse ovaries: excellent morphology,
      apoptosis detection, and spectroscopy.
AB  - BACKGROUND: Ovaries consist of numerous follicles, oocytes, and granulosa cells
      in different stages of development. Many of these follicles will undergo an
      apoptotic process during the lifetime of the animal. By using proper tissue
      preparation methods, the events within the whole ovary can be observed by using
      3D confocal microscopy. METHODS: Whole ovaries were stained with LysoTracker Red
      (LT), fixed with 4% paraformaldehyde (PF) and 1% glutaraldehyde (Glut),
      dehydrated with methanol (MEOH), and cleared with benzyl alcohol and benzyl
      benzoate (BABB). Using this tissue preparation technique, the ovary becomes
      relatively transparent, allowing its morphology to be observed with confocal
      microscopes. A spectral imaging system (PARISS) located on a conventional
      microscope was used to interpret the LT dye spectra and fixation products in the
      tissues with different excitation wavelengths. RESULTS: Apoptosis in the follicle
      was detected as clusters of intensely stained granulosa cells located in close
      proximity to the oocytes. The fixation with Glut and PF preserved morphological
      details, increased tissue fluorescence, thus increased the signal to noise of the
      background image. CONCLUSIONS: Thick tissues can be imaged after they are
      properly stained, aldehyde fixed, and BABB cleared. LT intensely stained single
      cells or clusters of apoptotic cells in the follicles and the nucleolus. Spectral
      differences between LT as an indicator of apoptosis and Glut-PF fixation was used
      to visualize ovarian morphology and apoptosis. The PARISS spectrophotometer
      revealed spectral peaks for LT at 609.6 nm and for Glut-PF at 471.3 nm. The
      proper use of the spectra from these fluorescence molecules is the foundation for
      high quality morphological images of apoptosis. By sequentially imaging the two
      probes with a 488 nm laser and a 543/568 nm laser, there was a reduction in
      fluorescent cross talk and an increase in image quality.

PMID- 16969805
TI  - Sensitivity measurement and compensation in spectral imaging.
AB  - BACKGROUND: The ImageStream system combines advances in CCD technologies with a
      novel optical architecture for high sensitivity and multispectral imaging of
      cells in flow. The sensitivity and dynamic range as well as a methodology for
      spectral compensation of imagery is presented. METHODS: Multicolored fluorescent
      beads were run on the ImageStream and a flow cytometer. Four single color
      fluorescent control samples of cells were run to quantify spectral overlap. An
      additional sample, labeled with all colors was run and compensated in six
      spectral channels. RESULTS: Analysis of empirical data for sensitivity and
      dynamic range matched theoretical predictions. The ImageStream system
      demonstrated fluorescence sensitivity comparable to a PMT-based flow cytometer. A
      methodology for addressing spectral overlap, individual pixel anomalies, and
      multiple imaging modalities was demonstrated for spectral compensation of K562
      cells. Imagery is shown pre- and post-compensation. CONCLUSIONS: Unlike intensity
      measurements made with conventional flow cytometers, object size impacts both
      dynamic range and fluorescence sensitivity in systems that utilize pixilated
      detection. Simultaneous imaging of alternate modalities can be employed to
      increase fluorescent sensitivity. Effective compensation of complex multimode
      imagery spanning six spectral bands is accomplished in a semi-automated manner.

PMID- 16969806
TI  - The Nikon C1si combines high spectral resolution, high sensitivity, and high
      acquisition speed.
AB  - Spectral imaging is a natural extension of the capabilities of confocal
      microscopes. The first confocal spectral imaging (CSI) instruments were able to
      acquire spectral data that allowed the emissions of overlapping fluorescent
      probes to be assigned to data channels representing a spectrum rather than a
      range of emission wavelengths. This marked a significant improvement over what
      could be done by channel series with standard confocal microscopes. However the
      performance of these earlier designs can fall short in one or more of the
      following areas; sensitivity, spectral resolution and reproducibility,
      acquisition speed, and unmixing accuracy. Nikon has recently introduced a new CSI
      instrument, C1si, that overcomes some of the more serious performance
      deficiencies of earlier designs through unique optical, electronic, and data
      handling advances. C1si uses a multianode photomultiplier tube (PMT) as the
      detector and typically acquires spectral data in a single scan. Sensitivity is
      enhanced over designs diffracting randomly polarized fluorescence by rotating the
      polarization of all emission photons to the S-plane, the plane for which the
      diffraction grating is most efficient. Three diffraction gratings are provided
      supporting wavelength sampling increments of 2.5, 5, and 10 nm. Improvements have
      been made in the digitization process to increase detection efficiency as well.
      C1si is calibrated to a high enough standard that it is possible to share and
      reproduce data between instruments. The algorithm implemented in the EZ-C1
      software is able to accurately and repeatedly unmix fluorescent probes with
      emission peaks separated by as little as 5 nm. It is possible to unmix probes
      with emission peaks separated by 20 nm with a 10-1 brightness difference. Three
      probes can be unmixed with emission peaks contained within a 20 nm range.
      Acquisition is fast enough and the sensitivity is sufficient for C1si to acquire
      more than 100 frames of spectral time series data without serious photobleaching.

PMID- 16969807
TI  - Hyperspectral imaging system using acousto-optic tunable filter for flow
      cytometry applications.
AB  - A major advantage of flow cytometry is its flexible and open instrument
      configuration, which is highly suitable for systems integration. This flexibility
      permits the coupling of auxiliary instrumentation that may offer the measurement
      of parameters other than those typically measured by this multiparameter
      measurement technique. On the basis of this advantage, we explore the principle
      and application of hyperspectral imaging (HSI), which has the potential to be a
      useful add-on feature to flow cytometry applications. Application of HSI to flow
      cytometry involves the acquisition of spatial information and rendering it in
      spectral form. In this work, we describe the development and application of an
      HSI system which provides both spectral and spatial information. Spectral
      information was generated by obtaining an entire spectrum of a single sample site
      within a wavelength region of interest, while spatial information was generated
      by recording a two-dimensional (2D) image of an area of the sample of interest at
      one specific wavelength. HSI is a promising additional feature to flow cytometry
      since it can provide both spatial (image format) and spectral information in
      addition to the multiparameter information already available from flow cytometry
      measurements.

PMID- 16969808
TI  - Spectral mapping tools from the earth sciences applied to spectral microscopy
      data.
AB  - BACKGROUND: Spectral imaging, originating from the field of earth remote sensing,
      is a powerful tool that is being increasingly used in a wide variety of
      applications for material identification. Several workers have used techniques
      like linear spectral unmixing (LSU) to discriminate materials in images derived
      from spectral microscopy. However, many spectral analysis algorithms rely on
      assumptions that are often violated in microscopy applications. This study
      explores algorithms originally developed as improvements on early earth imaging
      techniques that can be easily translated for use with spectral microscopy.
      METHODS: To best demonstrate the application of earth remote sensing spectral
      analysis tools to spectral microscopy data, earth imaging software was used to
      analyze data acquired with a Leica confocal microscope with mechanical spectral
      scanning. For this study, spectral training signatures (often referred to as
      endmembers) were selected with the ENVI (ITT Visual Information Solutions,
      Boulder, CO) "spectral hourglass" processing flow, a series of tools that use the
      spectrally over-determined nature of hyperspectral data to find the most
      spectrally pure (or spectrally unique) pixels within the data set. This set of
      endmember signatures was then used in the full range of mapping algorithms
      available in ENVI to determine locations, and in some cases subpixel abundances
      of endmembers. RESULTS: Mapping and abundance images showed a broad agreement
      between the spectral analysis algorithms, supported through visual assessment of
      output classification images and through statistical analysis of the distribution
      of pixels within each endmember class. CONCLUSIONS: The powerful spectral
      analysis algorithms available in COTS software, the result of decades of research
      in earth imaging, are easily translated to new sources of spectral data. Although
      the scale between earth imagery and spectral microscopy is radically different,
      the problem is the same: mapping material locations and abundances based on
      unique spectral signatures.

PMID- 16969809
TI  - Forensic visualization of foreign matter in human tissue by near-infrared
      spectral imaging: methodology and data mining strategies.
AB  - BACKGROUND: Rapidity of data acquisition, high image fidelity and large field of
      view are of tremendous value when looking for chemical contaminants or for the
      proverbial "needle in the haystack" - in this case foreign inclusions in
      histologic sections of biopsy or autopsy tissues. Near infrared chemical imaging
      is one of three chemical imaging techniques (NIR, MIR and Raman) based on
      vibrational spectroscopy, and provides distinct technical advantages for this
      application. METHODS: We have chosen to utilize and evaluate near infrared (NIR)
      imaging for studies of foreign materials in tissue because the experimental
      configuration is relatively simple, data collection is rapid, and large sample
      areas can be screened with high image fidelity and spatial resolution. RESULTS:
      We have shown that NIR imaging can readily find and identify silicone gel
      inclusions in biological tissue samples. Additionally, preliminary results
      indicate that spectral signatures in the data set are also potentially sensitive
      to structural changes in the surrounding tissue that may be induced by the
      foreign body. CONCLUSIONS: NIR chemical imaging is a powerful, non-destructive
      tool for localization and identifying foreign contaminants in biological tissue.
      Preliminary results indicate that NIR imaging is also sensitive enough to
      differentiate tissue types (perhaps based on collagen structural differences),
      and provide data on the spatial localization of these components.

PMID- 16969810
TI  - Spectral kinetics ratiometry: a simple approach for real-time monitoring of
      fluorophore distributions in living cells.
AB  - BACKGROUND: Spectral Imaging Microscopy is gaining attention in biological
      research. Most of the commercial systems in vogue employ linear spectral un
      mixing algorithms and/or spectral profile matching algorithms to extract the
      component spectral information from the measured specimen spectra. The need to
      accurately deconvolve multiple spectra with minimal cross-contamination is always
      accompanied by an increase in system complexity and cost. METHODS: We describe
      here a variant of the spectral waveform cross-correlation analysis (SWCCA) method
      where the master reference spectral library is constructed by composite spectra
      with varying ratios of component spectra, unlike the conventional spectral
      library where pure spectra form the components. We demonstrate that this spectral
      kinetics ratiometric approach gives realistic estimates of fluorophore
      distribution in living cells with a better spectral correlation as compared with
      pure component spectral libraries. RESULTS: Biological applications demonstrated
      in this article include acceptor photobleaching FRET, caspase activity during
      cell death and mitochondrial membrane polarization kinetics during substrate
      metabolism. CONCLUSIONS: Beyond the representative applications presented in this
      article, we think the proposed approach can be valuable in dynamic studies of a
      variety of other cellular processes such as pH oscillations, photobleaching and
      quenching kinetics. Besides giving better spectral correlation and real-time
      monitoring of biophysical processes in living cells, this method can serve as an
      economical solution for high-throughput spectral classification requirements.

PMID- 16969811
TI  - Increasing lanthanide luminescence by use of the RETEL effect.
AB  - BACKGROUND: Luminescent lanthanide complexes produce emissions with the narrowest
      known width at half maximum; however, their significant use in cytometry required
      an increase in luminescence intensity. The companion review, Leif et al.,
      Cytometry 2006;69A:767-778, described a new technique for the enhancement of
      lanthanide luminescence, the Resonance Energy Transfer Enhanced Luminescence
      (RETEL) effect, which increases luminescence and is compatible with standard
      slide microscopy. METHODS: The luminescence of the europium ion macrocyclic
      complex, EuMac, was increased by employing the RETEL effect. After adding the
      nonluminescent gadolinium ion complex of the thenoyltrifluoroacetonate (TTFA)
      ligand or the sodium salt of TTFA in ethanol solution, the EuMac-labeled sample
      was allowed to dry. Both a conventional arc lamp and a time-gated UV LED served
      as light sources for microscopic imaging. The emission intensity was measured
      with a CCD camera. Multiple time-gated images were summed with special software
      to permit analysis and effective presentation of the final image. RESULTS: With
      the RETEL effect, the luminescence of the EuMac-streptavidin conjugate increased
      at least six-fold upon drying. Nuclei of apoptotic cells were stained with DAPI
      and tailed with 5BrdUrd to which a EuMac-anti-5BrdU conjugate was subsequently
      attached. Time-gated images showed the long-lived EuMac luminescence but did not
      show the short-lived DAPI fluorescence. Imaging of DNA-synthesizing cells with an
      arc lamp showed that both S phase and apoptotic cells were labeled, and that
      their labeling patterns were different. The images of the luminescent EuMac and
      fluorescent DAPI were combined to produce a color image on a white background.
      This combination of simple chemistry, instrumentation, and presentation should
      make possible the inexpensive use of the lanthanide macrocycles, Quantum Dyes, as
      molecular diagnostics for cytological and histopathological microscopic imaging.

PMID- 16969813
TI  - A new configuration of the Zeiss LSM 510 for simultaneous optical separation of
      green and red fluorescent protein pairs.
AB  - The power and simplicity of genetically encoded fluorophores (fluorescent
      proteins, FPs) have drawn many molecular biologists to light microscopy. First
      generation FPs suffered from overlapping excitation and emission spectra, which
      limited their use together in pairs (Patterson et al., J Cell Sci 2001;114 (Part
      5):837-838). Image acquisition and processing techniques, collectively known as
      linear unmixing, have been developed to separate overlapping fluorescence signals
      encountered in the imaging of FP pairs and also in FRET. These specialized
      techniques are not without their potential drawbacks, including limitations on
      sensitivity and time-resolution for live cell imaging, and the risk of artifact
      in the hands of nonspecialists. With the advent of a new generation of red
      shifted FPs (Shaner et al., Nat Biotechnol 2004;22:1567-1572; Verkhusha and
      Lukyanov, Nat Biotechnol 2004;22:289-296) careful selection of excitation sources
      and emission filters obviate the need for linear unmixing when simple two channel
      imaging of FPs is required. Here we introduce a new configuration of the Zeiss
      LSM 510 laser scanning confocal microscope, optimized for live cell imaging of
      green fluorescent protein (GFP) together with spectral variants such as mRFP1 and
      mCherry using standard photo-multipliers. A 2 mW, 594 nm HeNe laser was chosen as
      the excitation source for the red FP. This wavelength efficiently excites the
      aforementioned red variants without limiting the detection range of GFP emission
      during simultaneous two-channel imaging. Compared to excitation of GFP and
      mCherry at 488 and 543 nm, excitation at 488 and 594 nm approximately doubles the
      sensitivity of GFP detection and eliminates bleed-through of GFP into the mCherry
      channel. However, sensitivity of mCherry detection is decreased by 30%,
      suggesting the need for red FPs having longer emission peaks. Practical
      advantages to the simultaneous optical separation of FPs with nonoverlapping
      emission spectra include simplicity, robustness, reduced risk of artifact, and
      increased sensitivity during live cell imaging.

PMID- 16969814
TI  - Spectral analysis of the DNA targeting bisalkylaminoanthraquinone DRAQ5 in intact
      living cells.
AB  - BACKGROUND: We report on the potential DNA binding modes and spectral
      characteristics of the cell-permeant far red fluorescent DNA dye, DRAQ5, in
      solution and bound within intact cells. Our aim was to determine the constraints
      for its use in flow cytometry and bioimaging. METHODS: Solution characteristics
      and quantum yields were determined by spectroscopy. DRAQ5 binding to nuclear DNA
      was analyzed using fluorescence quenching of Hoechst 33342 dye, emission
      profiling by flow cytometry, and spectral confocal laser scanning microscopy of
      the complex DRAQ5 emission spectrum. Cell cycle profiling utilized an EGFP-cyclin
      B1 reporter as an independent marker of cell age. Molecular modeling was used to
      explore the modes of DNA binding. RESULTS: DRAQ5 showed a low quantum yield in
      solution and a spectral shift upon DNA binding, but no significant fluorescence
      enhancement. DRAQ5 caused a reduction in the fluorescence intensity of Hoechst
      33342 in live cells prelabeled with the UV excitable dye, consistent with
      molecular modeling that suggests AT preference and an engagement of the minor
      groove. In vivo spectral analysis of DRAQ5 demonstrated shifts to longer
      wavelengths upon binding with DNA. Analysis of spectral windows of the dual
      emission peaks at 681 and 707 nm in cells showed that cell cycle compartment
      recognition was independent of the far red-near IR emission wavelengths
      monitored. CONCLUSIONS: The study provides new clues to modes of DNA binding of
      the modified anthraquinone molecule in vivo, and its AT base-pair selectivity.
      The combination of low quantum yield but high DNA affinity explains the favorable
      signal-to-noise profile of DRAQ5-nuclear fluorescence. The robust nature of cell
      cycle reporting using DRAQ5, even when restricted spectral windows are selected,
      facilitates the analysis of encroaching spectral emissions from other fluorescent
      reporters, including GFP-tagged proteins.

PMID- 16969815
TI  - Laser microdissection in translational and clinical research.
AB  - Laser microdissection (LMD) is now a well established method for isolating
      individual cells or subcellular structures from a heterogeneous cell population.
      In recent years, cell, DNA, RNA, and protein based techniques has been
      successfully coupled to LMD and important information has been gathered through
      the analysis of the genome, transcriptome, and more recently the proteome of
      individual microdissected cells. The aims of this review are to summarize and
      compare the principles of different laser microdissection instruments and
      techniques, to discuss sample preparation procedures for microdissection, and to
      provide wide variety of examples of translational/clinical research applications
      of LMD. Novel techniques specifically developed for the improved isolation of
      stained cells, living cells, or rare cells are also discussed.LMD has become an
      indispensable tool in the preparation of homogenous samples for sophisticated
      cell or molecular assays. Despite major technological advances, the labor
      requirements of LMD are still relatively high. However, understanding the
      advantages and disadvantages of LMD technology and associated sample preparation
      procedures may aid in the earlier introduction of this method into the routine
      clinical diagnostics.

PMID- 16969816
TI  - Automated detection of tunneling nanotubes in 3D images.
AB  - BACKGROUND: This paper presents an automated method for the identification of
      thin membrane tubes in 3D fluorescence images. These tubes, referred to as
      tunneling nanotubes (TNTs), are newly discovered intercellular structures that
      connect living cells through a membrane continuity. TNTs are 50-200 nm in
      diameter, crossing from one cell to another at their nearest distance. In
      microscopic images, they are seen as straight lines. It now emerges that the TNTs
      represent the underlying structure of a new type of cell-to-cell communication.
      METHODS: Our approach for the identification of TNTs is based on a combination of
      biological cell markers and known image processing techniques. Watershed
      segmentation and edge detectors are used to find cell borders, TNTs, and image
      artifacts. Mathematical morphology is employed at several stages of the
      processing chain. Two image channels are used for the calculations to improve
      classification of watershed regions into cells and background. One image channel
      displays cell borders and TNTs, the second is used for cell classification and
      displays the cytoplasmic compartments of the cells. The method for cell
      segmentation is 3D, and the TNT detection incorporates 3D information using
      various 2D projections. RESULTS: The TNT- and cell-detection were applied to
      numerous 3D stacks of images. A success rate of 67% was obtained compared with
      manual identification of the TNTs. The digitalized results were used to achieve
      statistical information of selected properties of TNTs. CONCLUSION: To further
      explore these structures, automated detection and quantification is desirable.
      Consequently, this automated recognition tool will be useful in biological
      studies on cell-to-cell communication where TNT quantification is essential.

PMID- 16969817
TI  - Metallurgical characterization, galvanic corrosion, and ionic release of
      orthodontic brackets coupled with Ni-Ti archwires.
AB  - In orthodontics, a combination of metallic alloys is placed into the oral cavity
      during medical treatment and thus the corrosion resistance and ionic release of
      these appliances is of vital importance. The aim of this study is to investigate
      the elemental composition, microstructure, hardness, corrosion properties, and
      ionic release of commercially available orthodontic brackets and Copper Ni-Ti
      archwires. Following the assessment of the elemental composition of the
      orthodontic wire (Copper Ni-Ti) and the six different brackets (Micro Loc,
      Equilibrium, OptiMESH(XRT), Gemini, Orthos2, and Rematitan), cyclic polarization
      curves were obtained for each material to estimate the susceptibility of each
      alloy to pitting corrosion in 1M lactic acid. Galvanic corrosion between the
      orthodontic wire and each bracket took place in 1M lactic acid for 28 days at 37
      degrees C and then the ionic concentration of Nickel and Chromium was studied.
      The orthodontic wire is made up from a Ni-Ti alloy with copper additions, while
      the orthodontic brackets are manufactured by different stainless steel grades or
      titanium alloys. All tested wires and brackets with the exception of Gemini are
      not susceptible to pitting corrosion. In galvanic corrosion, following exposure
      for 28 days, the lowest potential difference (approximately 250 mV) appears for
      the orthodontic wire Copper Ni-Ti and the bracket made up from pure titanium
      (Rematitan) or from the stainless steel AISI 316 grade (Micro Loc). Following
      completion of the galvanic corrosion experiments, measurable quantities of
      chromium and nickel ions were found in the residual lactic acid solution.

PMID- 16969818
TI  - Biocompatibility of resin-based dental materials applied as liners in deep
      cavities prepared in human teeth.
AB  - BACKGROUND: Since only a few data have been published concerning the effects of
      resinous dental materials on the pulp-dentin complex, the aim of this study was
      to evaluate the biocompatibility of resin-based materials applied as liners in
      deep cavities prepared in human teeth. METHODS: After preparing class V cavities,
      the following dental materials were applied on the axial walls: group 1,
      Vitrebond (VIT; 3M ESPE); group 2, Ultra-Blend Plus (UBP; Untradent); and group
      3, Clearfil SE Bond (CSEB; Kuraray). In group 4 (control), the hard-setting
      calcium hydroxide cement Dycal (CH; Caulk/Dentsply) was used. The teeth extracted
      at 7 days or between 30 and 85 days after the clinical procedures were processed
      for histological evaluation. RESULTS: For all the experimental and control
      groups, most of specimens exhibited no pulpal response or slight inflammatory
      reaction associated with slight tissue disorganization at 7-day period. Moderate
      inflammatory pulpal response occurred only in one tooth (RDT = 262 microm) of
      group 3 in which transdentinal diffusion of resin components was observed.
      CONCLUSION: The resin-based dental cements VIT and UBP as well as the bonding
      agent CSEB presented acceptable biocompatibility when applied in deep cavities
      prepared in sound human teeth.

PMID- 16969819
TI  - Spectral imaging: principles and applications.
AB  - BACKGROUND: Spectral imaging extends the capabilities of biological and clinical
      studies to simultaneously study multiple features such as organelles and proteins
      qualitatively and quantitatively. Spectral imaging combines two well-known
      scientific methodologies, namely spectroscopy and imaging, to provide a new
      advantageous tool. The need to measure the spectrum at each point of the image
      requires combining dispersive optics with the more common imaging equipment, and
      introduces constrains as well. METHODS AND RESULTS: The principles of spectral
      imaging and a few representative applications are described. Spectral imaging
      analysis is necessary because the complex data structure cannot be analyzed
      visually. A few of the algorithms are discussed with emphasis on the usage for
      different experimental modes (fluorescence and bright field). Finally, spectral
      imaging, like any method, should be evaluated in light of its advantages to
      specific applications, a selection of which is described. CONCLUSIONS: Spectral
      imaging is a relatively new technique and its full potential is yet to be
      exploited. Nevertheless, several applications have already shown its potential.

PMID- 16969820
TI  - Multispectral imaging in biology and medicine: slices of life.
AB  - Multispectral imaging (MSI) is currently in a period of transition from its role
      as an exotic technique to its being offered in one form or another by all the
      major microscopy manufacturers. This is because it provides solutions to some of
      the major challenges in fluorescence-based imaging, namely ameliorating the
      consequences of the presence of autofluorescence and the need to easily
      accommodate relatively high levels of signal multiplexing. MSI, which spectrally
      characterizes and computationally eliminates autofluorescence, enhances the
      signal-to-background dramatically, revealing otherwise obscured targets. While
      this article concentrates on examples derived from liquid-crystal tunable filter
      based technology, the intent is to showcase the advantages of multispectral
      imaging in general. Some technologies used to generate multispectral images are
      compatible with only particular optical configurations, such as point-scanning
      laser confocal microscopy. Band-sequential approaches, such as those afforded by
      liquid-crystal tunable filters (LCTFs), can be conveniently coupled with a
      variety of imaging modalities, which, in addition to fluorescence microscopy,
      include brightfield (nonfluorescent) microscopy as well as small-animal,
      noninvasive in-vivo imaging. Brightfield microscopy is the chosen format for
      histopathology, which relies on immunohistochemistry to provide molecularly
      resolved clinical information. However, in contrast to fluorescent labels,
      multiple chromogens, if they spatially overlap, are much harder to separate and
      quantitate, unless MSI approaches are used. In-vivo imaging is a rapidly growing
      field with applications in basic biology, drug discovery, and clinical medicine.
      The sensitivity of fluorescence-based in-vivo imaging, as with fluorescence
      microscopy, can be limited by the presence of significant autofluorescence, a
      limitation which can be overcome through the utilization of MSI.

PMID- 16969821
TI  - Spectral imaging microscopy web sites and data.
AB  - The Internet is enabling greater access to spectral imaging publications,
      spectral graphs, and data than that was available a generation ago. The spectral
      imaging systems discussed in this issue of Cytometry work because reagent and
      hardware spectra are reproducible, reusable, and provide input to spectral
      unmixing and spectral components recognition algorithms. These spectra need to be
      readily available in order to determine what to purchase, how to use it, and what
      the output means. We refer to several commercially sponsored and academic
      spectral web sites and discuss our spectral graphing and data sites. Sites
      include fluorescent dye graph servers from Invitrogen/Molecular Probes, BD
      Biosciences, Zeiss/Bio-Rad Cell Sciences, and filter set servers from Chroma
      Technology and Omega Optical. Several of these sites include data download
      capabilities. Recently, two microscope manufacturers have published on their web
      sites transmission curves for select objective lenses-crucial data for anyone
      doing multiphoton excitation microscopy. Notable among the academic sites,
      PhotoChemCAD 2.0 has over 200 dyes and a downloadable database/graphing program,
      and the USC-A Chemistry UV-vis Database displays absorption spectra of many dyes
      and indicators used in clinical histology and pathology. Our Fluorescent Spectra
      graphing/calculator site presents dyes, filters, and illumination data from many
      of these and additional sources. PubSpectra is our free download site which uses
      Microsoft Excel files as standardized human/machine readable format with over
      2,000 biomedical spectra. The principle that data is not subject to copyright
      provides a framework in which all scientific data should be made freely
      accessible.

PMID- 16969822
TI  - Biological responses to multilayered DNA-coatings.
AB  - This study was performed to evaluate the basic biological response to
      deoxyribonucleic acid (DNA)-based coatings for soft tissue implants. To that end,
      in vitro experiments were used to study their cytocompatibility, and in vivo
      subcutaneous implantation studies with transponders in a rat model were performed
      to evaluate their histocompatibility. The DNA-based coatings were fabricated
      using the electrostatic self-assembly technique using cationic poly-D-lysine or
      poly-allylamine hydrochloride and anionic DNA. Noncoated substrates served as
      controls. In vitro, the behavior of primary rat dermal fibroblasts was assessed
      in terms of cell proliferation and morphology. Both types of multilayered DNA
      coatings significantly increased rat dermal fibroblast proliferation without
      altering the morphological appearance of the cells. The tissue response to
      multilayered DNA-coatings was assessed using an in vivo rat model, in which
      transponders were inserted subcutaneously for 4 and 12 weeks. No macroscopic
      signs of inflammation or adverse tissue reactions were observed at implant
      retrieval. Histological analyses demonstrated a uniform tissue response to all
      types of implants. All implants were encapsulated in a fibrous tissue capsule
      without intervening inflammatory cells at the implant surface.
      Histomorphometrically, multilayered DNA-coatings induced fibrous tissue capsules
      with similar quality and thickness compared to noncoated controls. In addition,
      all fibrous tissue capsules showed similar expression of alpha-smooth muscle
      actin. This study demonstrates that multilayered DNA-coatings are cytocompatible
      and histocompatible, and justifies further research on their functionalization
      with biologically active compounds to modulate tissue responses.

PMID- 16969823
TI  - A modern biomaterial for adhesion prevention.
AB  - A biomaterial composed of carboxymethylcellulose, poly(ethylene oxide), and
      calcium can be prepared in a variety of ways to reduce fibrin deposition and
      adhesion formation. This biomaterial platform can be formulated into a flowable
      gel with tissue adherence appropriate for use in minimally invasive surgery. The
      device remains at the site of placement even in gravitationally dependent areas.
      A peridural formulation was shown in preclinical studies to be safe and effective
      in reducing adhesions to dura following spinal surgery. A peritoneal formulation
      used on pelvic organs following peritoneal cavity surgery was also shown to be
      safe and effective. A clinical feasibility study showed that patients with severe
      back pain and lower extremity weakness treated with the peridural formulation,
      applied over their nerve roots following laminectomy or laminotomy, experienced
      significantly reduced symptoms when compared with surgery-only controls. The
      peritoneal formulation was shown in two multicenter feasibility studies of women
      undergoing pelvic surgery to significantly reduce adhesion formation when
      compared with surgery-only controls. Confirmation of the feasibility studies
      awaits results from pivotal clinical trials. These formulations were safe,
      effective, and easy to use. This biomaterial provided a benefit to patients
      undergoing surgery where postsurgical adhesion formation is a concern.

PMID- 16969824
TI  - Polypeptide multilayer nanofilm artificial red blood cells.
AB  - Reliable encapsulation of hemoglobin (Hb) within polypeptide multilayer nanofilms
      has been achieved by a template-based approach, and protein functionality has
      been demonstrated postencapsulation. The method is general in scope and could be
      useful for many other encapsulants. Met-Hb was adsorbed onto 5 microm-diameter
      CaCO3 microparticles, and the Hb-coated particles were encapsulated within a
      multilayer nanofilm of poly(L-glutamic acid) (PLGA) and poly(L-lysine) (PLL) by
      layer-by-layer assembly. The CaCO3 templates were then dissolved within the
      PLGA/PLL nanofilms by addition of ethylenediaminetetraacetic acid. Encapsulation
      of Hb was proved by fluorescence microscopy, the pH-dependence of retention of Hb
      was determined by visible wavelength absorbance, and conversion of the
      encapsulated met-Hb to deoxy-Hb and oxy-Hb was demonstrated by spectroscopic
      analysis of the Soret absorption peak under various conditions. It thus has been
      shown that control of Hb oxygenation within polypeptide multilayer nanofilm
      artificial cells is possible, and that Hb thus encapsulated can bind, release,
      and subsequently rebind molecular oxygen. This work therefore represents an
      advance in the development of polypeptide multilayer film artificial red blood
      cells.

PMID- 16969825
TI  - Different outcomes in urethral reconstruction using elastin and collagen patches
      and conduits in rabbits.
AB  - OBJECTIVES: To study the feasibility of urethral reconstruction with two
      urethroplasty techniques using an elastin and collagen heterograft in rabbits.
      MATERIALS AND METHODS: Fifty-two male rabbits were studied. Two types of injury,
      (1) a 1.5 x 0.6 cm2 semicircumferential defect; (2) a 1.5 cm segmental defect of
      the penile urethra, were created and repaired using size-matched elastin and
      collagen patches or tubed conduits. Urethral repair by primary closure for the
      type 1 injury and a tubularized autologous bladder mucosal graft for the type 2
      injury served as controls. At 3 months, urethral diameter was measured with
      retrograde urethrography. The animals were then euthanized for histological
      examination. RESULTS: The postoperative complication rate was significantly
      higher in the urethral reconstructions using tubed collagen (83%) and elastin
      (50%) grafts compared to the patch onlay grafts (p = 0.001 for collagen and p =
      0.01 for elastin) and tubularized ABM (10%, p = 0.003 and 0.05, respectively). At
      the type 2 injury site, a dense circumferential fibrosis developed after all
      repairs. Only minimal ventral fibrosis presented in the type 1 injury repair. The
      intensity of chronic inflammation and fibrosis was greatest when collagen was
      used for the urethral repair. In the elastin urethral repairs the urethral
      diameter decreased significantly for the tubed repair compared to the patch onlay
      (p = 0.02). CONCLUSION: Urethral injury repair using elastin and collagen
      biomaterials is feasible in the rabbit model. The results of onlay urethroplasty
      using the elastin and collagen patches are significantly superior to those using
      the elastin and collagen tubed conduits.

PMID- 16969826
TI  - Influence of contamination on bonding to zirconia ceramic.
AB  - The purpose of this study was to investigate the influences of contaminations and
      cleaning methods on bonding to dental zirconia ceramic. After saliva immersion
      and using silicone disclosing agent, airborne-particle abraded ceramic specimens
      were cleaned with isopropanol (AL), acetone (AC), 37% phosphoric acid (PA),
      additional airborne-particle abrasion (AA), or only with water rinsing (SS).
      Airborne-particle abraded specimens without contaminations (CL) were used as
      control group. For chemical analysis specimens of all groups were examined with X
      ray photoelectron spectroscopy (XPS). Plexiglas tubes filled with composite resin
      were bonded to ceramic specimens using a phosphate-monomer containing composite
      luting resin. After 3-day water storage, tensile bond strengths (TBS) were
      tested. XPS analysis of group SS showed the presence of saliva and silicone (Si)
      contamination on the surface. The ratios of carbon/zirconium and oxygen/zirconium
      for groups PA and AA were comparable to those ratios obtained for group CL,
      indicating the removal of the organic saliva contamination. Airborne-particle
      abrasion and acetone completely removed Si contamination from ceramic surfaces.
      Isopropanol had little cleaning effect on the two contaminants. TBS (median +/-
      standard deviation) in MPa of the groups SS (11.6 +/- 3.1), AL (10.0 +/- 2.9),
      and AC (13.0 +/- 2.8) were statistically lower than those of groups PA (33.6 +/-
      5.5), AA (40.1 +/- 3.6), and CL (47.0 +/- 8.1) (p < 0.001), while no differences
      were found in TBS between groups AA and CL (p > 0.5). Contamination significantly
      reduced bond strengths to zirconia ceramic. Airborne-particle abrasion was the
      most effective cleaning method.

PMID- 16969827
TI  - A biodegradable copolymer for the slow release of growth hormone expedites
      scarring in diabetic rats.
AB  - In many diseases wound healing is impaired. This study was designed to establish
      whether the healing process in diabetes could be improved using a site-specific
      polymer delivery system containing hGH. The system was first optimized in in
      vitro experiments performed on cultured fibroblasts taken from healthy and
      diabetic rats and then tested in an incisional wound model created in the
      diabetic Wistar rat. In the in vitro experiments using cultured fibroblasts, cell
      viability, growth, and proliferation were determined, along with polymer
      degradation, hormone release rates and the expression of TGFbeta1 in the culture
      medium. For the in vivo experiments, polymer discs with/without GH were inserted
      through 3 cm incisions made on the backs of the animals. Wound specimens were
      obtained 7 and 30 days after surgery to evaluate inflammatory/apoptotic cells,
      metalloprotease expression and neoangiogenesis using microscopy and
      immunohistochemical techniques. The local administration of GH using a polymer
      delivery system did not affect the normal wound healing process. Conversely, when
      used in diabetic animals, epidermal and dermal repair was expedited. Our findings
      indicate that GH induces cell proliferation, enhances CD4(+) infiltration;
      increases extracellular matrix protein deposition; stimulates angiogenesis; and
      diminishes apoptosis at the diabetic wound site. These effects give rise to a
      comparable wound healing process to that observed in healthy animals.

PMID- 16969828
TI  - Photocrosslinkable hydrogel for myocyte cell culture and injection.
AB  - Conventional treatment options for myocardial infarction are limited by the
      inability of mature myocardium to regenerate after injury. Although functional
      improvements after injection of cells and growth factors have been demonstrated,
      the clinical utility of this procedure has been hampered by poor cell
      localization, low survival, and rapid clearance of injected growth factors. The
      main objective of this study was to evaluate the applicability of a hydrogel,
      based on photocrosslinkable chitosan and acryloyl-poly(ethylene glycol)-RGDS (Az
      chitosan/Acr-PEG-RGD) for myocyte cell culture and myocardial injection. Chitosan
      was modified with photoreactive azidobenzoic acid and Acr-PEG-RGD was synthesized
      by reacting YRGDS with an equimolar amount of acryloyl-PEG-N-hydroxysuccinimide.
      For injection and encapsulation each polymer was dissolved in Di-H(2)O (pH 6.4),
      the solutions were mixed and crosslinked by UV application (4 mW/cm(2)). C2C12
      myoblasts proliferated and differentiated on hydrogels containing 5 mM RGD but
      not on the pure photocrosslinked chitosan. In vitro, the crosslinked hydrogels
      retained 80% of encapsulated VEGF for 24 days. Live/dead staining of neonatal rat
      cardiomyocytes encapsulated into Az-chitosan/Acr-PEG-RGD hydrogels indicated high
      cell viability upon UV crosslinking. Ex vivo, we localized the hydrogel on the
      surface and in the ventricle wall of an adult rat heart by brief (2 min) UV light
      application.

PMID- 16969829
TI  - Deep rolling of titanium rods for application in modular total hip arthroplasty.
AB  - Compressive residual stresses are commonly introduced into the near-surface
      regions of morse taper junctions of modular hip endoprostheses to prolong fatigue
      life. An increasing number of publications report that contamination of shot
      peened surfaces can lead to enhanced corrosion and third body wear. This study
      evaluates deep rolling of titanium alloy rods as a possible alternative to shot
      peening. Ten rods of Ti6Al7Nb alloy with a diameter of 15 mm were deep rolled
      with various rolling parameters. The resulting surface topography and residual
      contamination was analyzed using a scanning electron microscope (SEM). The near
      surface residual stress states after deep rolling were characterized by means of
      X-ray diffraction. The roughness of the surfaces before deep rolling was about
      R(z) = 14 microm, and after deep rolling surface roughness values of R(z) 0.4-7.5
      microm were achieved. The results of the SEM and EDAX analyses of the sample
      surface showed no evidence of surface contamination by particles or abrasion
      products caused by any process. At a pressure of 300 bar, compressive stress
      reached the maximum of -1150 MPa at a depth of 0.1 mm. Deep rolling thus allows a
      smooth and particle-free surface to be obtained and therefore shows promise as a
      surface treatment for mating surfaces of morse tapers in modular hip
      endoprostheses.

PMID- 16969830
TI  - Urinary retention and sympathetic sphincter obstruction in axonal Guillain-Barre
      syndrome.
AB  - A 62-year-old woman with axonal Guillain-Barre syndrome developed weakness and
      urinary retention simultaneously. The retention failed to recover for 10 months
      even after she regained the ability to walk. The patient exhibited no postural
      hypotension. Videourodynamics showed that the retention was caused not by the
      bladder paralysis but rather by internal (sympathetic) sphincter obstruction,
      which is extremely uncommon in peripheral neuropathies. We started the patient on
      an alpha-adrenergic antagonist, urapidil, at 30 mg/day, and this led to
      successful relaxation of the urethra and reduced the postvoid residual from 200
      ml to less than 30 ml. The underlying mechanisms of urinary retention in our
      patient appeared to involve hyperactive lumbosacral sympathetic nerves. Urinary
      retention and sympathetic sphincter obstruction can thus be features of axonal
      Guillain-Barre syndrome.

PMID- 16969831
TI  - Hereditary neuropathy with liability to pressure palsy combined with schwannomas
      of the median and medial plantar nerves.
AB  - A 42-year-old woman was surgically treated for carpal tunnel syndrome, revealing
      schwannoma of the median nerve. A year later, she developed a tarsal tunnel
      syndrome. At time of this diagnosis, hereditary neuropathy with liability to
      pressure palsies (HNPP) was diagnosed genetically and a schwannoma of the medial
      plantar nerve was treated surgically. The occurrence of HNPP and schwannomas in
      the same patient might be purely coincidental, but it is tempting to speculate
      that they share a common genetic basis.

PMID- 16969832
TI  - Clinical variability in type I familial amyloid polyneuropathy (Val30Met):
      comparison between late- and early-onset cases in Portugal.
AB  - We compared early- with late-onset cases in 86 patients with familial amyloidotic
      polyneuropathy type I (FAP). Among these patients, 43 presented before age 50
      (early-onset) and 43 after this age (late-onset). Sex and geographical
      distribution were similar, although a family history of the disorder was more
      frequent in early-onset cases. In late-onset disease, autonomic dysfunction was
      less frequent, but organ involvement and severe neuropathic pain were more
      frequent. Neurophysiological measurements were similar. FAP is a cause of
      neuropathy in elderly patients, in particular in those presenting with
      neuropathic pain.

PMID- 16969833
TI  - Weekly oral prednisolone improves survival and strength in male mdx mice.
AB  - Although corticosteroids alleviate weakness in mdx mice, no long-term treatment
      has determined whether this benefit is maintained. We studied mdx mice forelimb
      grip strength and fatigue from 3 through 84 weeks and followed survival through
      104 weeks. The mdx mice were given twice weekly oral prednisolone (5 mg/kg)
      beginning at 3 or 4 weeks. Treated mdx mice survived longer than untreated mice.
      Between 3 and 10 weeks, treated and untreated mdx mice had similar strength.
      Between 10 and 24 weeks, strength and strength per gram body weight declined more
      slowly in treated than untreated mdx mice. Between 24 and 84 weeks, treated and
      untreated mdx mice declined in strength at the same rate, although treated mice
      remained stronger. Forelimb grip fatigue was present in untreated mdx mice at all
      time-points compared to wild-type and was not changed significantly by treatment.
      We have demonstrated long-term benefit of oral prednisolone in the mdx mouse
      model of Duchenne muscular dystrophy (DMD). As corticosteroids remain the most
      validated long-term treatment of DMD, this work may allow for better prediction
      of synergistic treatments likely to translate to effective improvement for boys
      with this progressive muscular dystrophy.

PMID- 16969834
TI  - Implementation and application of a continuous quality improvement (CQI) program
      for the cardiac catheterization laboratory: one institution's 10-year experience.
AB  - There is consensus that a continuous quality improvement (CQI) program is
      essential in optimizing patient outcomes in the cardiovascular catheterization
      laboratory. A CQI method was described in guidelines produced by the Society for
      Cardiovascular Angiography and Interventions (SCAI) in 1993 and 1997. However,
      little information is available in the medical literature to determine the
      implementation and application of this approach in a modern catheterization
      program. This presentation describes the lessons learned from one institution's
      10 year CQI experience by using the SCAI blueprint.

PMID- 16969835
TI  - Neuromuscular disorders in pregnancy.
AB  - Many neuromuscular conditions occur more frequently during pregnancy and include
      carpal tunnel syndrome, Bell's palsy, lumbosacral radiculopathy, meralgia
      paresthetica, intercostal neuralgia, and other compression neuropathies.
      Preexisting or coincident neuromuscular diseases, including demyelinating
      polyneuropathies, inflammatory muscle disease, myasthenia gravis, and inherited
      nerve and muscle disease present specific problems during pregnancy. We review
      management of neuromuscular disorders during pregnancy, labor, delivery, and the
      early postpartum period.

PMID- 16969836
TI  - Myeloid dendritic cells in inclusion-body myositis and polymyositis.
AB  - Dendritic cells (DCs), immune system cells central to the development of
      immunity, have not previously been reported in muscle in inclusion-body myositis
      (IBM). We performed immunohistochemical studies on muscle biopsy specimens from
      50 patients using monoclonal antibodies that distinguish two classes of DCs,
      myeloid DC and plasmacytoid DC. In 17 of 20 IBM and 9 of 10 polymyositis (PM)
      specimens, myeloid DCs were present in substantial numbers, frequently surrounded
      and sometimes invading otherwise intact myofibers, and were part of dense
      collections of cells that included T cells. Dermatomyositis muscle had more
      plasmacytoid DCs than myeloid DCs, whereas IBM and PM had greater numbers of
      myeloid DCs. The stellate morphology of myeloid DCs in dense collections of cells
      that included T cells suggests local intramuscular antigen presentation in IBM
      and PM.

PMID- 16969837
TI  - Rigidity and spasms from autoimmune encephalomyelopathies: stiff-person syndrome.
AB  - Stiff-person syndrome (SPS) is a disorder characterized by progressive muscle
      rigidity with superimposed painful muscle spasms and gait impairment due to
      continuous motor activity. Evidence has accumulated in favor of SPS representing
      an autoimmune, predominantly encephalomyelopathic disorder resulting from B-cell
      mediated clonal production of autoantibodies against presynaptic inhibitory
      epitopes on the enzyme glutamic acid decarboxylase (GAD) and the synaptic
      membrane protein amphiphysin. Recognition of the clinical spectrum of SPS is
      important, particularly the upper-limb, cervical, and cranial nerve involvement
      that occurs in paraneoplastic variants. The correlation between antibody levels
      and severity of disease offers evidence for a pathogenic role for the anti-GAD
      and anti-amphiphysin autoantibodies. The scarcity of neuropathological correlates
      stand in sharp contrast with the severity of the disability in affected
      individuals and suggests that functional impairment of inhibitory circuits
      without structural damage is sufficient to develop the full clinical spectrum of
      SPS. The rarity of this condition limits the feasibility of controlled clinical
      trials in the treatment of SPS, but the available evidence suggest that drugs
      that increase cortical and spinal inhibition such as benzodiazepines and drugs
      that provide immune modulation such as intravenous immunoglobulin,
      plasmapheresis, and prednisone are effective treatments.

PMID- 16969838
TI  - Reliable surrogate outcome measures in multicenter clinical trials of Duchenne
      muscular dystrophy.
AB  - We studied the reliability of a series of endpoints in an evaluation of subjects
      with Duchenne muscular dystrophy (DMD). The endpoints included quantitative
      muscle tests (QMTs), timed function tests, forced vital capacity (FVC), and
      manual muscle tests (MMT). Thirty-one ambulatory subjects with DMD (mean age 8.9
      years; range 5-16 years) were evaluated at eight sites by 15 newly trained
      evaluators as a test of interrater reliability of outcome measures. Both total
      QMT score [intraclass correlation coefficient (ICC) 0.96] and individual QMT
      assessments (ICC 0.85-0.96) were highly reliable. Forced vital capacity and all
      timed function tests were also highly reliable (ICC 0.97-0.99). MMT was the least
      reliable assessment method (ICC 0.61). These data suggest that primary surrogate
      outcome measures in large multicenter clinical trials in DMD should use QMT, FVC,
      or time function tests to obtain maximum power and greatest sensitivity.

PMID- 16969839
TI  - Sensory sparing patterns and the sensory ratio in acute inflammatory
      demyelinating polyneuropathy.
AB  - The relative preservation (sparing) of sural sensory nerve action potentials
      (SNAPs) is a useful diagnostic finding in patients with acute inflammatory
      demyelinating polyneuropathy (AIDP). However, recording of sural SNAPs is not
      always technically feasible, especially in obese, edematous, or elderly
      individuals. Hence, we systematically evaluated the predictive values of the
      commonly employed SNAPs in the diagnosis of AIDP within 2 weeks from onset of
      symptoms. Sensory sparing patterns and sensory ratios of the sural, radial,
      median, and ulnar SNAPs of AIDP patients were included in a retrospective and
      blinded analysis, and compared to patients with diabetic polyneuropathy (DPN) and
      controls. Logistic regression models for the sural plus radial SNAPs/median plus
      ulnar SNAPs (sensory ratio) were constructed. A sural sparing pattern was present
      only in the AIDP group (34.4%, P < 0.001). A radial sparing pattern did not
      discriminate the AIDP from the DPN groups. The sural/radial sensory ratio was
      useful to ascertain DPN, but did not discriminate AIDP from controls. The sensory
      ratio was higher in AIDP compared to DPN and controls and was an independent
      predictor for AIDP. This study implies that the sensory ratio is a useful
      predictor for the diagnosis of AIDP and may substitute for sural sparing in
      technically difficult situations.

PMID- 16969840
TI  - Percutaneous renal artery intervention for preservation of renal function:
      strategies for identification of "at-risk" patients.

PMID- 16969841
TI  - Transradial intervention for native fistula failure.
AB  - The native radiocephalic (Brescia-Cimino) fistula is usually constructed with an
      anastomosis of the cephalic vein and radial artery. Catheter interventions for
      native fistula failure have until now been performed via the transcephalic or
      transbrachial approach. Transradial intervention for native fistula failure was
      prospectively evaluated for a selected consecutive 11 patients. Six patients had
      a single lesion and 5 patients had double lesions. Twelve lesions were stenotic
      and 4 were occlusive with thrombus. Balloon angioplasty alone was successful in
      10 lesions. In thrombosed fistulas, 2 lesions underwent manual catheter-directed
      thrombo-aspiration and 2 further lesions underwent a combination of catheter
      directed thrombo-aspiration and mechanical thrombectomy. Cutting Balloon
      angioplasty was performed for 3 resistant venous stenoses and for 1 radial artery
      stenosis. Technical and clinical success were achieved in all patients. No vessel
      rupture or perforation was observed in this study, nor was distal embolization in
      the radial artery or symptomatic pulmonary embolism. No radial artery occlusion
      or fistula infection was seen during the follow-up. The primary patency rates
      were 82% at 3 months and 64% at 6 months. Transradial intervention for native
      fistula failure is considered safe and feasible in a selected population; yet
      requires further validation.

PMID- 16969842
TI  - Beyond coronary intervention.

PMID- 16969843
TI  - Promising though not yet proven: emerging strategies to promote myocardial
      salvage.
AB  - Remarkable advances in our ability to achieve early and sustained culprit vessel
      patency in acute myocardial infarction have been satisfying, but our enthusiasm
      must be tempered by the knowledge that the overall treatment strategy often
      leaves an inadequate long term clinical result. Early success of percutaneous
      therapy as judged at angiography does not ensure recovery of normal left
      ventricular function, the most important determinant of survival in acute
      myocardial infarction. That congestive heart failure and death still complicate
      apparently successful percutaneous procedures underscores the need to develop
      novel therapies which salvage jeopardized myocardium, limit infarct size and
      preserve left ventricular function. An ever-increasing body of data demonstrates
      a multifactorial mechanism of myocyte injury and microvascular collapse and also
      demonstrates that these injuries seem to have a profound impact on long-term
      outcomes. Given these findings, microvascular protection during the acute event
      has become the focus of a variety of emerging technologies. The goal of these
      mechanical and pharmacologic therapies is the restoration of normal metabolic
      function at the myocyte level. The acute pathologic mechanisms which contribute
      to sustained left ventricular dysfunction despite angiographically successful
      revascularization will be reviewed as will be several strategies being developed
      to counter these pathologic mechanisms.

PMID- 16969844
TI  - Favorable effect of balloon mitral valvuloplasty on the incidence of atrial
      fibrillation in patients with severe mitral stenosis.
AB  - BACKGROUND: The long-term effect of balloon mitral valvuloplasty (BMV) on the
      incidence of atrial fibrillation (AF) in patients with severe mitral stenosis
      (MS) remains undetermined. AIMS: To assess the effect of successful BMV on the
      incidence of chronic AF in patients with severe MS, compare the results with
      historical controls, and identify factors associated with AF in such patients.
      METHODS: Retrospective analysis of 382 consecutive patients with severe MS and in
      sinus rhythm (SR) who underwent successful BMV (post procedure mitral valve area
      (MVA) > or =1.5 cm(2), mitral regurgitation (MR) < or =2/4) at our hospital and
      followed-up for 1-15.6 (mean 5.6 +/- 3.9) years with clinical and
      echocardiographic examination. RESULTS: Thirty-four (8.9%) patients developed AF
      at follow-up (group A) and 348 patients (group B) remained in SR. At baseline,
      and in comparison with group B, patients who developed AF (group A) were older,
      had higher mitral echo score but equal MVA and left atrial (LA) size. The
      postprocedure MVA was smaller in group A (1.7 +/- 0.3 cm(2)) than in group B (2.0
      +/- 0.2 cm(2;) P = 0.002). At follow-up, and in comparison to group B, group A
      had smaller MVA (1.5 +/- 0.4 cm(2) vs 1.8 +/- 0.4 cm(2) P <0.0001), larger LA
      dimension (49.4 +/- 6.5 vs 42 +/- 6.5 mm; P <0.0001) and higher restenosis rate
      (35% vs 14%; P = 0.001). Multivariate logistic regression analysis identified age
      at follow-up (P < 0.0001), LA size at follow-up (P = 0.004), and MVA at follow-up
      (P = 0.006) as predictors of AF. CONCLUSIONS: This study demonstrated favorable
      effect of BMV on the incidence of AF (8.9%) in patients with severe MS in
      comparison with reported series (29%) of patients with severe MS with similar
      baseline characteristics who were not submitted to any intervention. The
      predictors of AF were age, larger LA, and smaller MVA, at follow-up.

PMID- 16969845
TI  - Non-infective prosthetic paravalvular leak: reducible complexity?

PMID- 16969846
TI  - Left atrial appendage septae not visualized with transesophageal
      echocardiography.
AB  - Left atrial appendage (LAA) filter implantation was attempted in an 89 year old
      male. The LAA size was estimated by transesophageal echocardiography (TEE).
      Complete LAA obliteration was not achieved. LAA angiography suggested that the
      LAA was multilobed, likely separated by a thin septae not seen with TEE. MRI or
      CT may be more appropriate imaging modalities to define LAA anatomy.

PMID- 16969847
TI  - Outcome of patients with acute coronary syndromes and moderate coronary lesions
      undergoing deferral of revascularization based on fractional flow reserve
      assessment.
AB  - OBJECTIVES: To determine the outcome of consecutive patients with and without
      acute coronary syndromes (ACS) in whom revascularization was deferred on the
      basis of fractional flow reserve (FFR). BACKGROUND: FFR < 0.75 correlates with
      ischemia on noninvasive tests and deferral of treatment on the basis of FFR is
      associated with low event rates in selected populations. Whether these low event
      rates apply to patients undergoing assessment of moderate stenoses in association
      with an ACS is not known and is an important clinical question. METHODS:
      Retrospective analysis and 12 month follow-up of consecutive, moderate (50-70%)
      de novo coronary lesions assessed with FFR. RESULTS: Revascularization was
      deferred in 120 lesions (111 patients) with FFR > or = 0.75. ACS was present in
      35 patients (40 lesions). The clinical, angiographic and coronary hemodynamic
      characteristics of patients with and without ACS were similar. Among the 35
      patients with ACS, there were 3 deaths, 1 MI, and 6 target vessel
      revascularizations (TVRs) (15% of lesions). Among the 76 patients without ACS,
      there were 5 deaths, 1 MI, and 7 TVR's (9% of lesions). CONCLUSIONS: Deferral of
      revascularization based on FFR in patients with ACS and moderate coronary
      stenoses is associated with acceptable and low event rates at 1 year.

PMID- 16969848
TI  - Day case transradial coronary angioplasty: a four-year single-center experience.
AB  - We examined the safety and feasibility of elective outpatient transradial
      coronary angioplasty (PCI). Four hundred and forty two patients underwent
      procedures over a 4-year period. Over 95% had an excellent angiographic result
      and 85% were discharged the same day. Radial access was successful in 417 (94%)
      patients. There were no major vascular complications. One patient died of a
      subacute stent thrombosis. Outpatient transradial PCI is safe and feasible for
      the majority of elective PCI cases.

PMID- 16969849
TI  - Histopathological findings of new in-stent lesions developed beyond five years.
AB  - We analyzed 14 cases of new lesions inside implanted bare-metal stents. In every
      case, there was no angiographic restenosis within 3 years, but a new lesion was
      observed inside a stented segment at long-term follow-up (>5 years). Fourteen
      cases were evaluated: 9 with Wiktor stents, 2 with Palmaz-Schatz stents, and 3
      with ACS Multilink stents. The interval from stent implantation to follow-up
      angiography was 63-147 months (89 +/- 23). Thirteen lesions were treated by
      percutaneous coronary intervention (PCI) and stenotic tissue was obtained by
      directional coronary atherectomy (DCA) in 10 cases. All retrieved samples were
      composed of newly developed atherosclerosis facing the healed neointimal layer,
      and four samples showed histopathological findings of acute coronary syndrome.
      Stent struts were retrieved in four cases and no inflammation was observed
      surrounding them. Qualitative and quantitative analysis of stent struts was
      performed in two cases that showed no metal corrosion. These findings suggest
      that new atherosclerotic progression occurred inside the implanted stent without
      peristrut inflammation.

PMID- 16969850
TI  - Late atheromatous degeneration of neointima after coronary stenting: an ounce of
      prevention.

PMID- 16969851
TI  - Is there an effect of flat-panel-based imaging systems on quantitative coronary
      and vascular angiography?
AB  - OBJECTIVES: To study the possible effects on quantitative coronary or vascular
      analyses (QCA and QVA) on images of a flat-panel-based (FP-based) system.
      BACKGROUND: Since a few years, more and more cardiovascular X-ray imaging systems
      are equipped with flat-panel detectors, replacing the conventional image
      intensifiers in combination with CCD cameras for the creation of the angiographic
      images. METHODS: To assess any differences in QCA and QVA results from these two
      types of digital X-ray imaging systems, we performed a quantitative comparison
      study on images of the Medis coronary and vascular phantom, respectively. All
      phantom images were acquired on both a FP-based and an image intensifier-based
      (II-based) imaging system with different system settings (3 different kV-levels
      and 4 field of view sizes). RESULTS: The QCA and QVA results showed that all the
      systematic and random errors for the subsets of the FP-based and II-based systems
      were very small and satisfy the QCA and QVA reference guidelines, though some of
      the subsets of the FP-based and II-based coronary and vascular phantom images
      demonstrate a statistically significant difference. However, given the small
      magnitude of these under- and overestimations under phantom conditions, these
      differences are considered clinically irrelevant. CONCLUSIONS: The image
      characteristics of the FP-based images do not have any significant influence on
      the results of QCA and QVA analyses. As a consequence, a further optimization of
      the contour detection algorithm is not necessary for FP-based images, and data
      from both II-based and FP-based X-ray imaging systems can be used collectively in
      (multicenter) clinical trials.

PMID- 16969852
TI  - Origin and distribution anomalies of the left anterior descending artery in
      70,850 adult patients: multicenter data collection.
AB  - OBJECTIVES: To present the clinical and angiographic properties of the left
      anterior descending artery anomalies. BACKGROUND: Coronary artery anomalies are
      discovered in less than 1% of angiography series. Since the number of
      angiographies and coronary bypass operations are increasing significantly every
      day, these anomalies are of clinical importance. However, data about left
      anterior descending artery anomalies in literature is still scarce. METHODS: We
      reviewed the records of 70,850 patients who had undergone coronary angiographies
      at 4 different cardiology center from 1999 to 2005 years. RESULTS: Major
      congenital coronary anomalies were discovered in 171 of these cases (0,24%). The
      mean age of these patients was 61 +/- 11 (18-84) years. Ninety nine patients
      (58%) were male. Left anterior descending artery was involved in 12 patients
      (0.017%). In nine patients with the anomalous LAD there were concomittant
      congenital coronary artery anomalies. Concurrent coronary artery anomalies
      encountered were double left anterior descending artery type 4 (2 cases), double
      left anterior descending artery type 4 with double right coronary artery (1),
      double right coronary artery (1), double circumflex artery with anomalous left
      anterior descending artery (1), circumflex artery from right sinus of Valsalva
      (1), separate septal perforator and myocardial bridging of posterior descending
      artery (1), intercoronary communication, and ostial atresia of the left anterior
      descending artery and anomalous circumflex artery (1). CONCLUSION: Our series is
      the biggest series where relatively sufficient clinical and angiographic
      information about the LAD anomalies were provided.

PMID- 16969853
TI  - Systemic immunosuppressive therapy inhibits in-stent restenosis in patients with
      renal allograft.
AB  - BACKGROUND: Cyclosporine is used routinely for prophylaxis for renal allograft
      rejection. In experimental animal studies, cyclosporine had been shown to inhibit
      smooth muscle cell proliferation during the arterial response to injury. We
      investigated whether systemic immunosuppression may inhibit in-stent restenosis
      in renal transplant patients undergoing coronary stenting. METHODS: From 1993 to
      2003, 33 renal transplant patients with 45 coronary lesions and 37 dialysis
      patients with 52 lesions underwent coronary stenting using bare metal stents at
      our center. We followed all patients clinically for a mean period of 37 +/- 31
      months and 40 patients angiographically at 14 +/- 15 months after coronary
      intervention. Cyclosporine was combined with corticosteroids in 32 patients and
      one patient received tacrolimus instead of cyclosporine. RESULTS: The baseline
      clinical and angiographical characteristics were similar and the success rate of
      the procedure was 100% in both groups. In renal transplant group, the mean dose
      of cyclosporine was 192.5 +/- 68 mg/day and the blood cyclosporine level at the
      time of procedure was 152.9 +/- 51.5 ng/mL. The rate of in-stent restenosis was
      7.1% in renal transplant group and 57.1% in dialysis group (P < 0.0001). The mean
      late loss was 0.47 +/- 0.57 mm in renal transplant group when compared with 1.51
      +/- 1.09 mm in dialysis group (P = 0.004). The overall rate of major adverse
      cardiac events (MACEs) was 6.1% in renal transplant group and 35.1% in dialysis
      group (P < 0.0001). CONCLUSIONS: Renal transplant patients receiving combined
      immunosuppressive agents showed markedly low rates of in-stent restenosis and
      MACE after coronary revascularization with stent. We consider that this result
      may be related to the ability of combined immunosuppressive therapy to inhibit
      inflammatory reaction and vascular smooth muscle cell proliferation induced by
      coronary stenting.

PMID- 16969854
TI  - A heterozygous effect for PINK1 mutations in Parkinson's disease?
AB  - OBJECTIVE: To investigate the significance of PINK1 mutations in sporadic
      Parkinson's disease (PD). METHODS: We determined the frequency of PINK1 mutations
      by direct sequencing in a large series of PD patients with apparently sporadic
      disease (n = 768). RESULTS: Twelve heterozygous mutations were identified, nine
      in PD patients and three in control subjects. INTERPRETATION: Given the
      difficulty in interpreting the pathogenic significance of the heterozygous
      mutations that have already been reported in parkin and DJ-1, we first determined
      the frequency of heterozygous PINK1 mutations in the general population by
      sequencing a large number of control subjects (n = 768), then subsequently
      assessed their functional significance by examining their effects on stress
      induced alterations to the mitochondrial membrane potential (DeltaPsim). We
      demonstrate an enrichment of heterozygous mutations in sporadic PD patients
      compared with matched control subjects (1.2% in PD vs 0.4% in control subjects).
      Furthermore, we show that they adversely affect DeltaPsim in a similar way to the
      familial G309D mutation. Although it remains difficult to conclusively
      demonstrate the pathogenicity of heterozygous mutations, the results of this
      study and the previously reported subclinical nigrostriatal dysfunction in
      carriers of heterozygous PINK1 mutations suggest the possibility that these
      heterozygous mutations are a significant risk factor in the development of later
      onset PD.

PMID- 16969855
TI  - Pseudoocclusion of the popliteal artery: "won't get fooled again" (Peter Townsend
      1971).

PMID- 16969856
TI  - Percutaneous closure of prosthetic paravalvular leaks: case series and review.
AB  - BACKGROUND: Paravalvular leaks (PVLs) are a well-recognized complication of
      prosthetic valve replacement. Most are asymptomatic and benign, but some may
      cause symptoms due to a large regurgitant volume or hemolysis. Medical therapy is
      palliative, while reoperation carries significant morbidity and mortality.
      Percutaneous transcatheter closure techniques, now routinely applied in the
      management of pathological cardiac and vascular communications, may be adaptable
      to PVL closure, potentially offer symptomatic relief. METHODS: We reviewed our
      experience with attempted percutaneous closure of PVLs, using data from medical
      and procedural records. RESULTS: Between 2001 and 2004, 14 procedures were
      performed in 10 patients, all under general anesthesia, with transesophageal and
      radiographic guidance. Mitral (9) and aortic (1) valve replacements were
      involved, both mechanical and bioprosthetic. A variety of devices were used,
      including atrial septal occluders, patent ductus arteriosus occluders, and coils
      (all of label use). Six had a single procedure, which was technically successful
      in four: in two, the PVL could not be crossed. Four underwent a second procedure,
      which was technically successful in three; in one the previously deployed device
      was dislodged necessitating urgent, but ultimately uneventful, surgical removal
      and leak repair. One patient had transient severe hemolysis, which resolved after
      1 week. At 1-year follow-up (9/10 pts) three had died, five had sustained
      symptomatic improvement while 1 patient with a residual leak still required
      regular blood transfusions. CONCLUSIONS: Percutaneous closure of PVLs is time
      consuming but feasible in selected patients, with a reasonable degree of
      technical and clinical success. A second procedure may be necessary and a variety
      of complications can occur.

PMID- 16969857
TI  - Atrial septostomy using a butterfly stent in a patient with severe pulmonary
      arterial hypertension.
AB  - We describe a patient with severe pulmonary artery hypertension and refractory
      right heart failure who underwent "butterfly" stent atrial septostomy guided by
      intracardiac ultrasound. This technique may be superior to previously reported
      blade and balloon septostomy because it allows creation of an atrial septal
      defect of a precise predetermined diameter. The patient's systemic blood flow and
      clinical status improved significantly after the procedure, allowing her to be
      accepted as a candidate for lung transplantation.

PMID- 16969858
TI  - Use of Palmaz stents in a newborn with congenital aneurysms and coarctation of
      the abdominal aorta.
AB  - Anomalies of the abdominal aorta are rare in the pediatric population limiting
      the reported knowledge base from which management decisions can be made. A 3-week
      old male with congenital abdominal aortic coarctation and multiple aneurysms
      presented with malignant hypertension. We report the safe deployment of
      overlapping Palmaz stents using a 4-French catheter delivery system with
      significant relief of the coarctation gradient and restoration of adequate renal
      perfusion.

PMID- 16969859
TI  - Pathogenesis of cardiac conduction disorders in children genetic and
      histopathologic aspects.
AB  - Fetal dysrhythmias are usually transient. Abnormal fetal rates and rhythms during
      labor are "functional." Fetal dysrhythmias may be associated with congenital
      heart disease and fetal hydrops. Bradycardia is usually related to fetal
      distress; supraventricular tachycardia, atrial flutter, and atrial fibrillation
      may be associated with severe congestive heart failure. Ventricular fibrillation
      is rare in the fetus and infant and is usually associated with myocardial
      necrosis with perimembranous septal defect; the nonbranching atrioventricular
      (AV) bundle may have an aberrant position and result in cardiac arrhythmia. Wolff
      Parkinson-White syndrome with conduction abnormalities and left ventricular
      hypertrophy (LVH) is due to an accessory pathway that bypasses the AV sulcus and
      results in faster conduction. Carnitine deficiency may be primary or secondary
      and may result in cardiac arrhythmia. Histiocytoid cardiomyopathy is
      characterized by cardiomegaly, incessant ventricular tachycardia, and frequently
      sudden death. Arrhythmogenic right ventricular dysplasia (ARVD) results in
      ventricular tachycardia and left bundle branch block. Noncompaction of the left
      ventricle predisposes to potentially fatal arrhythmias. Long Q-T syndromes (LQTS)
      are a heterogeneous group of disorders with many genetic mutations. Brugada
      syndrome is an autosomal dominant trait with right bundle branch block and ST
      elevation. Barth syndrome is an X-linked disorder with dilated cardiomyopathy,
      cyclic neutropenia and skeletal myopathy. Hypertrophic cardiomyopathy in infancy
      may be related to metabolic diseases, particularly glycogen storage diseases; the
      familial form predisposes to sudden death. Arrhythmias following cardiac surgery
      may occur after closure of a ventricular septal defect (VSD) or damage to the
      conduction system.

PMID- 16969860
TI  - Impaired visual search in drivers with Parkinson's disease.
AB  - OBJECTIVE: To assess the ability for visual search and recognition of roadside
      targets and safety errors during a landmark and traffic sign identification task
      in drivers with Parkinson's disease (PD). METHODS: Seventy-nine drivers with PD
      and 151 neurologically normal older adults underwent a battery of visual,
      cognitive, and motor tests. The drivers were asked to report sightings of
      specific landmarks and traffic signs along a four-lane commercial strip during an
      experimental drive in an instrumented vehicle. RESULTS: The drivers with PD
      identified significantly fewer landmarks and traffic signs, and they committed
      more at-fault safety errors during the task than control subjects, even after
      adjusting for baseline errors. Within the PD group, the most important predictors
      of landmark and traffic sign identification rate were performances on Useful
      Field of View (visual speed of processing and attention) and Complex Figure Test
      Copy (visuospatial abilities). Trail Making Test (B-A), a measure of cognitive
      flexibility independent of motor function, was the only independent predictor of
      at-fault safety errors in drivers with PD. INTERPRETATION: The cognitive and
      visual deficits associated with PD resulted in impaired visual search while
      driving, and the increased cognitive load during this task worsened their driving
      safety.

PMID- 16969861
TI  - Early-onset low-grade papillary carcinoma of the bladder associated with Apert
      syndrome and a germline FGFR2 mutation (Pro253Arg).

PMID- 16969862
TI  - Prion protein (PRNP) genotypes in frontotemporal lobar degeneration syndromes.

PMID- 16969863
TI  - Elejalde syndrome--a case report.
AB  - Elejalde syndrome (McKusick 200995), also known as acrocephalopolydactylous
      dysplasia, is a rare condition. We describe a sixth patient with this syndrome
      which is characterized by craniosynostosis and hyperproliferation of fibroblasts
      in many tissues including skin, liver, kidney, and pancreas. The cause of the
      syndrome is the homozygous state of an autosomal recessive mutation. We present a
      hypothesis that Elejalde syndrome might be associated with an inactivating FGFR
      gene mutation.

PMID- 16969864
TI  - Chromosome 10q24.3-qter deletion associated with left-sided first branchial arch
      defect, diaphragmatic eventration, and duplicated renal pelvis.

PMID- 16969865
TI  - Adherence to a Mediterranean dietary pattern and risk of Alzheimer's disease.

PMID- 16969866
TI  - Aortic rupture following a covered stent for coarctation: delayed recognition.
AB  - Primary stenting for aortic coarctation is frequently used in adult patients.
      Aortic rupture remains an infrequent complication. A number of strategies,
      including the use of covered stents, have been proposed to reduce the risk of
      this catastrophic complication. We describe a 51-year-old female who underwent
      stenting of aortic coarctation using a covered stent, which was complicated by
      aortic rupture. Treatment consisted of placement of an additional covered stent
      to seal the site of aortic disruption. The prevention and management of aortic
      rupture complicating aortic coarctation stenting are discussed.

PMID- 16969868
TI  - Somatic mosaicism for an HRAS mutation causes Costello syndrome.
AB  - De novo heterozygous HRAS point mutations have been reported in more than 81
      patients with Costello syndrome (CS), but genotype/phenotype correlation remains
      incomplete because the majority of patients share a common mutation, G12S, seen
      in 65/81 (80%). Somatic HRAS mutations have previously been identified in solid
      tumors, and mutation hot spots related to a gain-of-function effect of the gene
      product are known. The germline mutations causing CS occur at these hot spots and
      convey a gain-of-function effect, thus accounting for the greatly increased
      cancer risk. Diagnostic testing for HRAS mutations is now available and the
      identification of a mutation in a patient with consistent clinical findings
      confirms a diagnosis of CS. It is not clear yet if the absence of an HRAS
      mutation precludes a diagnosis of CS. Because there is a significant overlap in
      the clinical findings of Costello, cardio-facio-cutaneous, and Noonan syndromes,
      diagnostic uncertainty remains in patients lacking an HRAS mutation. We report
      here on a female with findings suggestive of CS in whom mutation analysis
      performed with standard techniques on white blood cell derived DNA did not show
      an HRAS mutation. However, analysis of DNA derived from three independently
      collected buccal swabs showed a sequence change qualitatively consistent with the
      G12S mutation. Allelic quantitation showed the presence of the mutation in
      approximately 25%-30% of the sampled buccal cells. In this patient, standard
      technology failed to identify the disease causing mutation on DNA derived from a
      blood sample, highlighting the potential pitfalls in the interpretation of
      negative mutation studies. This is the first reported CS patient mosaic for the
      common HRAS mutation, likely due to a somatic mutation occurring very early in
      fetal development.

PMID- 16969869
TI  - Mitochondrial dysfunction in Stuve-Wiedemann syndrome in a patient carrying an
      ND1 gene mutation.

PMID- 16969870
TI  - Bladder exstrophy and Epstein type congenital macrothrombocytopenia: evidence for
      a common cause?

PMID- 16969871
TI  - A family with X-linked optic atrophy linked to the OPA2 locus Xp11.4-Xp11.2.
AB  - Autosomal dominant optic atrophy (ADOA) is the most common inherited optic
      atrophy. Clinical features of ADOA include a slowly progressive bilateral loss of
      visual acuity, constriction of peripheral visual fields, central scotomas, and
      color vision abnormalities. Although ADOA is the most commonly inherited optic
      atrophy, autosomal recessive, X-linked, mitochondrial, and sporadic forms have
      also been reported. Four families with X-linked optic atrophy (XLOA) were
      previously described. One family was subsequently linked to Xp11.4-Xp11.2 (OPA2).
      This investigation studied one multi-generation family with an apparently X
      linked form of optic atrophy and compared their clinical characteristics with
      those of the previously described families, and determined whether this family
      was linked to the same genetic locus. Fifteen individuals in a three-generation
      Idaho family underwent complete eye examination, color vision testing, automated
      perimetry, and fundus photography. Polymorphic markers were used to genotype each
      individual and to determine linkage. Visual acuities ranged from 20/30 to 20/100.
      All affected subjects had significant optic nerve pallor. Obligate female
      carriers were clinically unaffected. Preliminary linkage analysis (LOD score =
      1.8) revealed that the disease gene localized to the OPA2 locus on Xp11.4-Xp11.2.
      Four forms of inherited optic neuropathy, ADOA, autosomal recessive optic atrophy
      (Costeff Syndrome), Leber hereditary optic neuropathy, and Charcot-Marie-Tooth
      disease with optic atrophy, are associated with mitochondrial dysfunction. Future
      identification of the XLOA gene will reveal whether this form of optic atrophy is
      also associated with a mitochondrial defect. Identification of the XLOA gene will
      advance our understanding of the inherited optic neuropathies and perhaps suggest
      treatments for these diseases. An improved understanding of inherited optic
      neuropathies may in turn advance our understanding of acquired optic nerve
      diseases, such as glaucoma and ischemic optic neuropathy.

PMID- 16969872
TI  - BRCA1/2 testing in hereditary breast and ovarian cancer families III: risk
      perception and screening.
AB  - This study aimed to ascertain whether cancer risk perception changed following
      the offer and subsequent receipt of BRCA1/2 results and to evaluate breast and
      ovarian screening practices in testers and non-testers. Members of thirteen HBOC
      families were offered BRCA1/2 testing for a known family mutation. Perceived risk
      for developing breast cancer, ovarian cancer or for carrying the familial BRCA1/2
      mutation, was assessed at baseline and again at 6-9 months following the receipt
      of test results. Breast and ovarian cancer screening data were obtained at both
      time-points. A total of 138 women participated and 120 (87%) chose to be tested
      for a known familial mutation. Twenty-eight women (24%) were identified as
      carriers and their perceived ovarian cancer risk and their perception of being a
      mutation carrier increased (P = 0.01 for both). Those testing negatives had a
      significant decrease in all dimensions of risk perception (P < 0.01). Regression
      analysis showed test results to be strong predictors of follow-up risk perception
      (P = 0.001), however, they were not predictors of screening practices at follow
      up. Testers were more likely to have completed a clinical breast exam following
      testing than decliners. Mammography was positively associated with baseline
      adherence, age, and intrusive thoughts. Ovarian cancer worries only predicted
      pelvic ultrasound screening post-testing. Baseline practices and psychological
      factors appear to be stronger predictors of health behavior than test results.

PMID- 16969875
TI  - Stent implantation as a stabilization technique in supracardiac total anomalous
      pulmonary venous connection.
AB  - A 6-week-old male presented in-extremis with obstructed supra-cardiac total
      anomalous pulmonary venous connection. Balloon dilation and stent implantation in
      the stenotic segment of the vertical vein relieved the obstruction until the
      patient was stable enough to undergo surgical repair. An unusual form of
      extrinsic vertical vein compression was found at surgery.

PMID- 16969873
TI  - A fourth locus for hereditary hemorrhagic telangiectasia maps to chromosome 7.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is a genetically and clinically
      heterogeneous multisystem vascular dysplasia. Mutations of the endoglin and
      ACVRL1 genes are known to cause HHT. However, existence of HHT families in which
      linkage to these genes has been excluded has suggested that other gene(s) can
      cause HHT in some families. Recently, a family was reported to be linked to
      chromosome 5q, the HHT3 locus. Here we report on linkage results on a family with
      classic features of HHT, albeit a less severe phenotype with regards to epistaxis
      and telangiectases, in which linkage to HHT1, HHT2, and HHT3 is ruled out. Whole
      genome linkage analysis and fine mapping results suggested a 7 Mb region on the
      short arm of chromosome 7 (7p14) between STR markers D7S2252 and D7S510. We
      obtained a maximum two point LOD score of 3.60 with the STR marker D7S817. This
      region was further confirmed by haplotype analysis. These findings suggest the
      presence of another gene causing HHT (HHT4). The features in this family that
      strongly suggest the presence of a hereditary, multisystem vascular dysplasia
      would be easily missed during the typical evaluation and management of a patient
      with an AVM. This family helps emphasize the need to obtain a very detailed,
      targeted medical and family history for even mild, infrequent but recurring
      nosebleed, subtle telangiectases. Further studies of the candidate region and the
      identification of the gene responsible for the vascular anomalies in this family
      will add to our understanding of vascular morphogenesis and related disorders.

PMID- 16969876
TI  - Percutaneous transluminal coronary angioplasty in a two-month old with coronary
      stenosis presenting as congenital cardiomyopathy: acute results and intermediate
      follow-up.
AB  - Congenital or nonsurgically acquired obstructive coronary artery disease in
      infancy is exceedingly rare, and previous reports of catheter-based therapies in
      very young patients have been solely in patients having undergone arterial switch
      or other cardiovascular surgical procedures. We describe a previously unreported
      cause for ventricular dysfunction and heart failure in an infant, isolated
      congenital circumflex coronary artery stenosis, and successful treatment with
      percutaneous transluminal coronary angioplasty. Technical considerations,
      immediate results, and 3-year follow-up are provided.

PMID- 16969877
TI  - Use of percutaneous transluminal septal myocardial ablation for relief of outflow
      tract obstruction in cardiac amyloidosis: a novel therapeutic target.
AB  - Cardiac amyloidosis typically presents with diastolic heart failure, but
      asymmetrical septal hypertrophy with outflow tract obstruction has been
      described. We illustrate the case of a 71-year-old woman with biopsy-proven
      cardiac amyloidosis and severe medical comorbidities with refractory severe heart
      failure who had asymmetric septal hypertrophy, systolic anterior motion (SAM) of
      the mitral valve, and a resting left ventricular outflow tract gradient of 86 mm
      Hg, increasing to 102 mm Hg on Valsalva maneuver. She underwent percutaneous
      transluminal septal myocardial ablation (PTSMA) with a dramatic resolution of her
      SAM and outflow tract obstruction, confirmed by intracavitary pressure wire
      measurements. PTSMA is technically feasible in this context, and correction of
      outflow tract obstruction may represent a new therapeutic target in cardiac
      amyloidosis.

PMID- 16969878
TI  - Transcatheter closure of perimembranous ventricular septal defects using the
      amplatzer membranous VSD occluder: immediate and midterm results of an
      international registry.
AB  - OBJECTIVE: To report the immediate and midterm results of transcatheter closure
      of perimembranous ventricular septal defect (PmVSD) using the Amplatzer
      membranous VSD occluder (AMVSD). METHODS: Between April 2002 and August 2004, 100
      patients underwent an attempt of percutaneous device closure of PmVSD using the
      AMVSD in 24 international centers. The median age was 9.0 years (0.7-58 years)
      and the median weight was 27.5 kg (7-121 kg). RESULTS: A device was successfully
      deployed in 93/100 (93%) patients. Reasons for procedural failure were an
      increased gradient across the left ventricle outflow tract in one patient, aortic
      regurgitation in 2 patients, and inability to securely position the device in 4
      patients. The median VSD size by TEE was 7.0 mm (1.5-13 mm), median device size
      10 mm (4-16 mm) and median fluoroscopy time 22.1 min (8.9-96.0 min). Weight below
      10 kg (P = 0.0392), inlet extension of the VSD (P = 0.0139) and aortic cusp
      prolapse into the VSD (P = 0.0084) were significantly associated with a lower
      procedural success. Patients have been followed up for a median of 182 days (1
      763 days). There were no procedure-related deaths. Complications were encountered
      in 29/100 (29%) patients, including rhythm or conduction anomalies in 13 patients
      (two with complete heart block requiring permanent pacemaker implantation), new
      or increased aortic (9 patients) or tricuspid (9 patients) regurgitation, most of
      which were classified as trivial or mild. Patients with a weight below 10 kg had
      a significantly higher incidence of adverse events than patients with a weight
      above 10 kg (58.3% versus 25.0%, P = 0.0285). Immediately after device release
      complete closure of the defect was present in 54/93 (58.1%) patients, increasing
      to 46/55 (83.6%) patients at 6-months follow-up (P = 0.0012). Left ventricle end
      diastolic diameter decreased from a median of 44 mm prior to device closure to a
      median of 39 mm at 6-months postprocedure (P = 0.0015). CONCLUSION: Closure of
      PmVSDs using the AMVSD occluder is safe and effective. However, longer follow-up
      period is warranted prior to the wide spread use of this device.

PMID- 16969879
TI  - Safety and efficacy of bioabsorbable magnesium alloy stents in porcine coronary
      arteries.
AB  - OBJECTIVE: We aimed to determine the safety and efficacy of biobasorbable
      magnesium alloy stents in porcine coronary arteries. Bioabsorbable magnesium
      stents carry the potential to overcome the limitations posed by permanent
      metallic stents such as chronic inflammation, late stent thrombosis, prolonged
      antiplatelet therapy, and artifacts when imaged by multislice-computed tomography
      or magnetic resonance imaging. METHODS: Magnesium alloy stents or stainless steel
      stents were randomly deployed in coronary arteries of domestic or minipigs.
      Domestic pigs were sacrificed at 3 days (n = 2) or 28 days, and minipigs at 3
      months. RESULTS: At 3 days, magnesium alloy stents were intact, but started to
      show signs of degradation by 28 days. There was no evidence of stent particle
      embolization, thrombosis, excess inflammation, or fibrin deposition. At 28 days
      and 3 months, neointimal area was significantly less in magnesium alloy stent
      segments (2.44 +/- 0.88 mm(2) and 1.16 +/- 0.19 mm(2)) as compared with the
      stainless steel stent segments (5.03 +/- 1.5 mm(2) and 1.72 +/- 0.68 mm(2), P <
      0.001 and 0.02). Quantitative coronary analysis indicates that percentage area
      stenosis and percentage diameter stenosis in magnesium alloy stent segments
      improved significantly at 3 months as compared to 28 days. Despite decreased
      neointimal hyperplasia, lumen area of the magnesium alloy stented vessels did not
      improve significantly. CONCLUSION: Magnesium alloy stents are safe and are
      associated with less neointima formation; however, reduced neointima did not
      result in larger lumen.

PMID- 16969880
TI  - Polymer matrix effects on the nonlinear optical response of incorporated
      chromophore: new analytical models.
AB  - A new approach aimed at the modeling of the nonlinear optical (NLO) response of a
      dipole chromophore incorporated into a locally anisotropic, deformable,
      polarizable polymer matrix is suggested. The general continuum methodology is
      used with a specific cavity ansatz being employed; the cavity is chosen to be
      conformal to the characteristic ellipsoid of the generalized permittivity tensor
      of the polymer medium. The suggested ansatz allows the electrostatic boundary
      value problem to be solved analytically, and the local field experienced by the
      chromophore in the polymer electret to be found. Four analytically solvable
      models, which correspond to two singular and two nonsingular models, are
      considered; in two of them the chromophore is characterized by singular dipole
      and quadrupole moments; the other two use the approximation of the electric
      moment of the chromophore with that of the polarized ellipsoid. The relation
      between the macroscopic polymer properties and the microscopic characteristics of
      the NLO chromophore is established. The compliance of the obtained formulas for
      the local field with those of the classical Onsager approach is analyzed, and
      their specific features are considered.

PMID- 16969881
TI  - Stability and electrostatics of mercaptoundecanoic acid-capped gold nanoparticles
      with varying counterion size.
AB  - The solubility of charged nanoparticles is critically dependent on pH. However,
      the concentration range available with bases such as NaOH is quite narrow, since
      the particles precipitate due to compression of the electric double layer when
      the ionic strength is increased. The stability of mercaptoundecanoic acid-capped
      Au nanoparticles is studied at a set pH using the hydroxide as base and different
      cations of various sizes. The counterions used are sodium (Na(+)),
      tetramethylammonium (TMA(+)), tetraethylammonium (TEA(+)), and tetrabutylammonium
      (TBA(+)). The particles precipitate in the 70-90 mM range with Na(+) as the
      counterion, but with quaternary ammonium hydroxides the particles are stable even
      in concentrations exceeding 1 M. The change in solubility is linked to a strongly
      adsorbed layer on the surface of the ligand shell of the nanoparticles. The
      increased concentration range obtained with TEAOH is further used to facilitate
      thiol exchange which occurs at a greater extent than would be achieved in NaOH
      solution.

PMID- 16969883
TI  - Recent advances in catalytic enantioselective intermolecular C-H
      functionalization.

PMID- 16969882
TI  - Density functional embedded cluster study of Cu(4), Ag(4) and Au(4) species
      interacting with oxygen vacancies on the MgO(001) surface.
AB  - Cu(4), Ag(4), and Au(4) species adsorbed on an MgO(001) surface that exhibits
      neutral (F(s)) and charged (F(s) (+)) oxygen vacancies have been studied using a
      density functional approach and advanced embedding models. The gas-phase rhombic
      planar structure of the coinage metal tetramers is only moderately affected by
      adsorption. In the most stable surface configuration, the plane of the tetramers
      is oriented perpendicular to the MgO(001) surface; one metal atom is attached to
      an oxygen vacancy and another one is bound to a nearby surface oxygen anion. A
      very similar structural motif was recently found on defect-free MgO(001), where
      two O(2-) ions serve as adsorption sites. Following the trend of the interactions
      with the regular MgO(001) surface, Au(4) and Cu(4) bind substantially stronger to
      F(s) and F(s) (+) sites than Ag(4). This stronger adsorption interaction at
      oxygen vacancies, in particular at F(s), is partly due to a notable accumulation
      of electron density on the adsorbates. We also examined the propensity of small
      supported metal species to aggregate to adsorbed di-, tri- and tetramers.
      Furthermore, we demonstrated that core-level ionization potentials offer the
      possibility for detecting experimentally supported metal tetramers and
      characterizing them structurally with the help of calculated data.

PMID- 16969884
TI  - Interfacing electrocatalysis and biocatalysis with tungsten carbide: a high
      performance, noble-metal-free microbial fuel cell.

PMID- 16969885
TI  - Crystallographic shear structures as a route to anion-deficient perovskites.

PMID- 16969886
TI  - Insights into the mechanism of methanol-to-olefin conversion at zeolites with
      systematically selected framework structures.

PMID- 16969887
TI  - Intercalation of organic molecules into vanadium(IV) benzenedicarboxylate:
      adsorbate structure and selective absorption of organosulfur compounds.

PMID- 16969888
TI  - Total synthesis of (+)-phyllantidine.

PMID- 16969889
TI  - Contact-active antimicrobial coatings derived from aqueous suspensions.

PMID- 16969890
TI  - Polyazidopyrimidines: high-energy compounds and precursors to carbon nanotubes.

PMID- 16969891
TI  - Tree-based model checking for logistic regression.
AB  - A tree procedure is proposed to check the adequacy of a fitted logistic
      regression model. The proposed method not only makes natural assessment for the
      logistic model, but also provides clues to amend its lack-of-fit. The resulting
      tree-augmented logistic model facilitates a refined model with meaningful
      interpretation. We demonstrate its use via simulation studies and an application
      to the Pima Indians diabetes data.

PMID- 16969892
TI  - Correction for regression dilution bias using replicates from subjects with
      extreme first measurements.
AB  - The least squares estimator of the slope in a simple linear regression model will
      be biased towards zero when the predictor is measured with random error, i.e.
      intra-individual variation or technical measurement error. A correction factor
      can be estimated from a reliability study where one replicate is available on a
      subset of subjects from the main study. Previous work in this field has assumed
      that the reliability study constitutes a random subsample from the main study. We
      propose that a more efficient design is to collect replicates for subjects with
      extreme values on their first measurement. A variance formula for this estimator
      of the correction factor is presented. The variance for the corrected estimated
      regression coefficient for the extreme selection technique is also derived and
      compared with random subsampling. Results show that variances for corrected
      regression coefficients can be markedly reduced with extreme selection. The
      variance gain can be estimated from the main study data. The results are
      illustrated using Monte Carlo simulations and an application on the relation
      between insulin sensitivity and fasting insulin using data from the population
      based ULSAM study. In conclusion, an investigator faced with the planning of a
      reliability study may wish to consider an extreme selection design in order to
      improve precision at a given number of subjects or alternatively decrease the
      number of subjects at a given precision.

PMID- 16969893
TI  - Optimal designs for estimating the most successful dose.
AB  - There has been much recent interest in phase I/II dose finding designs in which
      information on both toxicity and efficacy is used. Unlike the classic phase I
      dose finding design in which the aim is to identify the MTD (maximum tolerated
      dose corresponding to some percentile of acceptable toxicity), a phase I/II dose
      finding study aims to locate the most successful dose (MSD), i.e. the dose which
      maximizes the product of the probability of seeing no toxicity together with the
      probability of seeing a therapeutic response). In this work we present an
      abstract theoretical design for this purpose. We call this design a 'virtual'
      design. The virtual design, conceptually similar to that developed for phase I
      designs alone, is based on a bivariate response. The design has optimal
      properties in that the current estimates of both probability of toxicity and
      those for response achieve the Cramer-Rao bound for every dose level. Unhappily,
      the virtual design is not available for practical use but its use can be
      exploited in theoretical investigations in much the same way as one uses the
      Cramer-Rao bound for unbiased estimators, i.e. a tool which enables us to see how
      much room for improvement may exist for any given real design. Via examples taken
      from the literature on phase I/II dose finding we illustrate how this technique
      can provide us with further insight on the relative performance of competing
      designs.

PMID- 16969894
TI  - Random changepoint modelling of HIV immunologic responses.
AB  - We propose a changepoint model for the analysis of longitudinal CD4 T-cell counts
      for HIV infected subjects following highly active antiretroviral treatment. The
      profile of CD4 counts for each subject follows a simple, 'broken stick'
      changepoint model, with random subject-specific parameters, including the
      changepoint. The model accounts for baseline covariates. The longitudinal CD4
      records are censored at the time of the subject going off-study-treatment. This
      is a potentially informative drop-out mechanism, which we address by modelling it
      jointly with the CD4 count outcome. The drop-out model incorporates terms from
      the CD4 model, including the changepoint. The estimation is done in a Bayesian
      framework, with implementation via Markov chain Monte Carlo methods in the
      WinBUGS software. Model selection using DIC indicates that the data support the
      complex random changepoint and informative censoring model.

PMID- 16969895
TI  - [Nitrous oxide sedation].

PMID- 16969896
TI  - Local malpractice environments cause large variations in cesarean rates.

PMID- 16969897
TI  - [Pharmacological treatment of vascular cognitive impairment].
AB  - Vascular dementia is second most common cause of dementia. The paper highlights
      the most important trends in pharmacological treatment of vascular dementia.
      Result of a clinical trial of some agents appears to be promising. Pentoxifyline
      appears to be useful in multi-infarct vascular dementia. Nimodipine produced
      improvement in subcortical dementia. Some other agents like ginkgo biloba,
      acetylocholinesterase inhibitors, memantine and other also have shown mild
      benefit or at least were associated with some stabilization of dementia.

PMID- 16969898
TI  - [Osteoporosis risk factors among patients with schizophrenia].
AB  - The etiopathogenesis, risk factors and indications for prevention and treatment
      of osteoporosis in patients with schizophrenia are presented. Accelerated
      decrease in bone mineral density (BMD) is mostly attributed to antypsychotics
      (drug-induced hyperprolactinemia and decrease in levels of estrogen and
      testosterone), insufficient calcium intake, low physical activity and limited
      exposure to sunshine, alcohol and tobacco intake, polidypsia. Clinical symptoms
      of osteoporosis (eg. vertebral fractures) develop very slowly and in patients
      with schizophrenia are very rarely diagnosed. Many of risk factors (especially
      adequate choice of pharamcotherapy and monitoring of BMD) might be prevented in
      order to decrease the prevalence of osteoporosis in population of patients with
      schizophrenia.

PMID- 16969899
TI  - [The role of endothelial cells and endothelial precursor cells in angiogenesis].
AB  - Endothelium plays a key role in maintenance of vascular homeostasis in human
      organism. According to new data endothelial cells and hematopoietic cells have a
      common precursor in prenatal life--a hemangioblast, which explains the fact of
      sharing the same determinants on the surface of both type of cells. Circulating
      endothelial precursors were identified in adults and this suggests that
      hemangioblasts may be present not only during embriogenesis. In some clinical
      situations the increased numbers of endothelial cells and endothelial precursors
      were noted, and especially in patients with neoplastic diseases, which is
      probably the result of increased angiogenesis. Endothelial precursors are thought
      to be the promice for therapeutic purposes in future--to increase local
      angiogenesis.

PMID- 16969900
TI  - [Angiogenesis and endothelial cells in blood neoplasms].
AB  - This paper contains a review of present opinions on neoplastic angiogenesis with
      a special attention to hematologic malignancies. Methods of the evaluation of
      angiogenesis were discussed. The participation of circulating endothelial cells
      and endothelial precursors in angiogenesis was shown. The most known
      antiangiogenic agents were presented.

PMID- 16969901
TI  - [Tropical malaria--danger for persons visiting endemic areas].
AB  - Malaria continues to be a wide-spread infection in tropical areas. According to
      World Health Organization, malaria is present in over 100 countries, populated by
      over 3 bln people. Malaria morbidity in these areas is difficult to estimate.
      Tropical malaria caused by Plasmodium falciparum is responsible for more than 95%
      of fatal cases. Other Plasmodium species able to infect humans are P. vivax, P.
      ovale and P. malariae, typically responsible for more prolonged course of the
      disease, with possibility of late relapse, but rarely resulting in fatal outcome.
      We present a case of tropical malaria, illustrating wide spectrum of
      complications associated with P. falciparum infection, especially in cases of
      massive parasitemia.

PMID- 16969902
TI  - [Surprisingly positive effect of palliative CAP chemotherapy of bone
      disseminated, undifferentiated carcinoma of unknown primary origin in patient
      with low performance status according to WHO].
AB  - The paper presents the case of a 58-year old male with low performance status (3
      according to WHO) diagnosed with bone-disseminated, undifferentiated carcinoma of
      unknown primary origin in April 2001. The patient was given reduced dosage CAP
      chemotherapy (cisplatin 40 mg/m2, doxorubicin 40 mg/m2, cyclophosphamide 40
      mg/m2, every 21 days). A total number of 12 treatment courses were administered,
      reaching summary admissible dosage of doxorubicin. The patient's condition
      improved in the course of treatment - pain symptoms and levels of tumor
      biomarkers decreased significantly, while performance status increased.
      Chemotherapy was completed in December 2001. Patient status was stabile till
      March 2004. Presently the level of tumor biomarkers are increasing but it is not
      accompanied with metastasis or primary focus manifestation. Although the
      described patient undoubtedly belonged to the group with poor prognosis, the
      treatment applied resulted with surprisingly positive effect.

PMID- 16969903
TI  - Hyperglycaemic spikes as a risk factor of diabetic complications.

PMID- 16969904
TI  - Modeling of primary prevention of the development of type 2 diabetes.

PMID- 16969905
TI  - [Lack of prognostic significance of carcinoembryonic antigen (CEA) preoperative
      serum levels in patients with advanced larynx cancer].
AB  - The purpose of this study was to identify the relationship between preoperative
      serum levels of carcinoembryonic antigen (CEA) and clinicopathological features
      in advanced stage of larynx cancer. The mean CEA serum concentrations were below
      cutoff value, which exclude the CEA as a serum marker in diagnosis of larynx
      cancer. However, significant correlations were found between CEA levels and tumor
      size, lymph node metastasis and clinical stage of the disease. The pretreatment
      CEA level was increased above cut-off value only in 6% of tested patients and
      thereby is not a prognostic factor in larynx cancer.

PMID- 16969906
TI  - [Risk factors and frequency of postoperative nausea and vomiting in patients
      operated under general anesthesia].
AB  - INTRODUCTION: Postoperative nausea and vomiting belong to fairly frequent
      postoperative complications, but they occupy a distant position on the list of
      complications, which most probably result from a general conviction that they do
      not pose a direct threat to patients. OBJECTIVE: The objective of this work is
      specification of factors facilitating occurrence of postoperative nausea and
      vomiting, and determination of frequency of their occurrence in patients operated
      under general anesthesia. MATERIAL AND METHODS: Questionnaire about the
      occurrence of postoperative nausea and vomiting (PONV), was carried out and
      included 253 adult sick persons (102 female and 151 male patients), in the age
      between 23-76 (average 42.3 +/- 6.1 years), who had undergone operative procedure
      in the field of abdominal and urology surgery, orthopedic, thyroid surgery and
      laryngological, ophthalmology and plastic surgery, under general anesthesia. The
      questionnaire form included preoperative characteristics of a patient (age, sex,
      smoking, motion sickness and migraine headaches in history, and PONV occurring
      earlier), type of operative procedure, used anesthetic agents, and analgesic
      agents applied in postoperative analgesia. The anesthesiologist administering
      anesthetic was not informed about the investigation carried out and did not
      receive any additional pieces of advice regarding the type of applied anesthetic
      agents or the method of conducting postoperative analgesia. Visual Analogue Scale
      (VAS) was used in the evaluation of nausea. Nausea and vomiting were assessed
      every two hours within the first postoperative 12 hours and every 4 hours for the
      next 24 hours. Nausea and vomiting were treated as two separate complications.
      RESULTS: Nausea itself occurred in 22.7% of patients; whereas vomiting in 13.2%.
      Both symptoms occurred in 14.2% of patients. Nausea occurred 4.1 +/- 0.8 hours
      after operation; whereas vomiting after 5.3 +/- 1.1 hours. Women suffered more
      often than men from (R = 0.678 p < 0.001). The same was registered for non
      smokers (nausea: R = 0.623, vomiting: R = 0.437), and for the patients suffering
      from PONV earlier (R = 0.421 for nausea, and R=0.331 for vomiting). PONV also
      occurred more often in cases of obese patients (p < 0.002) and the patients
      anesthetized by younger anesthetists (p < 0.002). Clear relation between the
      frequency of postoperative nausea and vomiting occurrence and the type of
      operative procedure was also noticed. The relation appeared to be the strongest
      (R = 0.531; p < 0.001) in case of the sick who underwent abdominal and
      laryngological procedures (R= 0.421; p < 0.02), as well as ophthalmologic (R=
      0.407; p < 0.02) procedures. However, the relation was the weakest in case of the
      sick who underwent orthopedic procedures (R =0.127; p < 0.02). The correlation
      between anesthesia induction agents and frequency of PONV was not observed. PONV
      was significantly more frequent in case of the sick receiving postoperative
      opioids than those who received nonsteroid anti-inflammatory drugs. CONCLUSIONS:
      (1) PONV is more frequent in women than in men. The same refers to non-smokers,
      suffering from migraine headaches, motion sickness, as well as obesity and
      suffering from PONV earlier. (2) The frequency of postoperative vomiting in the
      patients with nausea is higher by 65.2% than in the patients without nausea. (3)
      A clear relation between the frequency of postoperative nausea and vomiting
      occurrence and the type of operative procedure was noticed. It was the strongest
      in the sick who underwent orthopedic procedures. (4) The correlation between
      anesthesia induction agents and PONV was not observed.

PMID- 16969908
TI  - [Toxoplasmosis--epidemiology, clinical manifestation and infection in pregnant
      women].
AB  - Toxoplasma gondii infection is one of the most popular human zoonosis. Presented
      is the epidemiology and clinical symptoms of toxoplasmosis with particular
      attention to infection during pregnancy. The paper presents the life cycle of
      Toxoplasma gondii, routes of transmission and clinical manifectations. The scheme
      of diagnostic and terapeutic procedures in case of infection during pregnancy is
      discussed. Congenital infection, serologic diagnostics and clinical symptoms have
      been described. Treatment of congenital toxoplasmosis is also presented.

PMID- 16969907
TI  - [Influence of early stage of chronic renal disease on risk of cardiac diseases
      and stroke].
AB  - Cardiovascular diseases are the main cause of death among people with kidney
      diseases. The early stage of chronic kidney disease, with mild decrease of
      glomerular filtration rate (GFR) and small increase of creatinine concentration
      in serum and/or occurrence of microalbuminuria, is related to the increase of
      cardiovascular morbidity and mortality. Kidney insufficiency is also
      independently connected with the risk of stroke. Patients with early stage of
      kidney insufficiency should be qualified as those in a cardiovascular high risk
      group.

PMID- 16969909
TI  - Consumers, HSAs don't mix...yet they want change. Consumer values inconsistent
      with new plans: study. Study: Americans worry over affordability of care.

PMID- 16969910
TI  - A focus on finance. High profile resignations highlight CFO pressures.

PMID- 16969911
TI  - [Do you worry about the health of your future colleagues?].

PMID- 16969912
TI  - Mental activity seen in a brain gravely injured.

PMID- 16969913
TI  - Transcriptional modulation of some Staphylococcus aureus iron-regulated genes
      during growth in vitro and in a tissue cage model in vivo.
AB  - Staphylococcus aureus can proliferate in iron-limited environments such as the
      mammalian host. The transcriptional profiles of 460 genes (iron-regulated,
      putative Fur-regulated, membrane transport, pathogenesis) obtained for S. aureus
      grown in iron-restricted environments in vitro and in vivo were compared in order
      to identify new iron-regulated genes and to evaluate their potential as possible
      therapeutic targets in vivo. Iron deprivation was created in vitro by 2,2
      dipyridyl, and in vivo, S. aureus was grown in tissue cages implanted in mice.
      Bacterial RNA was obtained from each growth condition and cDNA probes were co
      hybridized on DNA arrays. Thirty-six upregulated and 11 downregulated genes were
      commonly modulated in animals and in the low-iron medium. Real-time PCR confirmed
      the iron-dependent modulation of four novel genes (SACOL0161, 2170, 2369, 2431)
      with a Fur box motif. Some genes expressed in the dipyridyl medium were not
      expressed in vivo (e.g., copA, frpA, SACOL1045). Downregulated genes included an
      iron-storage protein gene and genes of the succinate dehydrogenase complex,
      reminiscent of a small RNA-dependent regulation thus far only demonstrated in
      Gram-negative bacteria. The expression of iron-regulated genes in distinct low
      iron environments provided insight into their relative importance in vitro and in
      vivo and their usefulness for vaccine and drug development.

PMID- 16969914
TI  - Burden of influenza in healthy children and their households.

PMID- 16969915
TI  - Effect of osmolality on net fluid absorption in non-infected and ETEC-infected
      piglet small intestinal segments.
AB  - In the small intestinal segment perfusion model the effect of osmolality on net
      fluid absorption in enterotoxigenic Escherichia coli (ETEC)-infected and non
      infected small intestinal segments of piglets was investigated. In ETEC-infected
      segments net fluid absorption was reduced. Lowering the osmolality from 375 to
      150 mOsmol/l by reducing sodium chloride concentrations increased net fluid
      absorption. There was a linear relationship between osmolality and net fluid
      absorption for both non-infected and ETEC-infected segments. Below 150 mOsmol/l
      the inverse relationship between osmolality and net fluid absorption disappeared.
      Substitution of sodium chloride with mannitol decreased net fluid absorption
      since mannitol cannot be actively absorbed. In ETEC-infected segments perfused
      with oral rehydration solution net fluid absorption significantly increased
      compared to a sodium chloride solution of similar osmolality, probably because of
      the high glucose concentration. Supplying hypotonic sodium chloride fluids to
      piglets can be beneficial in replenishing water and electrolyte losses in case of
      infectious diarrhoea.

PMID- 16969916
TI  - Spotlight: Martin  Rothman, FRCP, FESC.

PMID- 16969917
TI  - Hypoxic pulmonary vasoconstriction is/is not mediated by increased production of
      reactive oxygen species.

PMID- 16969918
TI  - Hypoxic pulmonary vasoconstriction is/is not mediated by increased production of
      reactive oxygen species.

PMID- 16969919
TI  - Hypoxic pulmonary vasoconstriction is/is not mediated by increased production of
      reactive oxygen species.

PMID- 16969920
TI  - Hypoxic pulmonary vasoconstriction is/is not mediated by increased production of
      reactive oxygen species.

PMID- 16969921
TI  - Evaluation of single and double centrifugation tube methods for concentrating
      equine platelets.
AB  - The aim of this study was to evaluate single and double centrifugation tube
      methods for concentrating equine platelets. Whole blood samples were collected
      from clinically normal horses and processed by use of single and double
      centrifugation tube methods to obtain four platelet concentrates (PCs): PC-A, PC
      B, PC-C, and PC-D, which were analyzed using a flow cytometry hematology system
      for hemogram and additional platelet parameters (mean platelet volume, platelet
      distribution width, mean platelet component concentration, mean platelet
      component distribution width). Concentrations of transforming growth factor beta
      1 (TGF-beta(1)) were determined in all the samples. Platelet concentrations for
      PC-A, PC-B, PC-C, and PC-D were 45%, 44%, 71%, and 21% higher, respectively,
      compared to the same values for citrated whole blood samples. TGF-beta(1)
      concentrations for PC-A, PC-B, PC-C, and PC-D were 38%, 44%, 44%, and 37% higher,
      respectively, compared to citrated whole blood sample values. In conclusion, the
      single and double centrifugation tube methods are reliable methods for
      concentrating equine platelets and for obtaining potentially therapeutic TGF
      beta(1) levels.

PMID- 16969922
TI  - Age-associated changes in distribution of the P2X2 receptor in  the major pelvic
      ganglion of the male rat.
AB  - P2X purinoceptors constitute a group of ligand-gated ion channels one of which,
      the P2X2 receptor has previously been described in neurons within autonomic
      ganglia, including the major pelvic ganglion (MPG). Earlier work strongly
      suggests that age-associated attrition of sympathetic but not parasympathetic MPG
      neurons occurs but there have been no investigations of age-related changes in
      P2X2 receptor expression in autonomic ganglia or to determine whether the
      receptor is localised in one or both of the two MPG neuronal subpopulations. In
      the current study, immunocytochemistry was employed to label cells expressing the
      P2X2 receptor in the MPG from young and aged male Wistar rats. By combining P2X2
      receptor immunocytochemistry with the immunolocalisation of tyrosine hydroxylase
      (TH), the numbers of sympathetic (TH+) and parasympathetic (TH-) neurons
      expressing the P2X2 receptor were determined. In young rats P2X2 receptor
      expression was found in 93.08+/-3.2% of TH- (parasympathetic) neurons. In aged
      rats a similar analysis revealed no significant difference in the number of TH-
      neurons expressing the P2X2 receptor. In contrast a significant increase in the
      number of TH+ sympathetic neurons expressing P2X2 was observed in the MPG of aged
      rats (10.70+/-2.26%) in comparison to the young group (2.38+/-0.78%). Age-related
      changes in the numbers of small intensely fluorescent (SIF) cells which were
      highly P2X2 positive were also quantified, revealing a small reduction in number
      with age. This study has demonstrated the preferential localisation of P2X2
      receptors to parasympathetic MPG neurons and suggests that purinergic
      transmission in the pelvic organs maybe largely unaffected by ageing.

PMID- 16969923
TI  - Who gets to choose? Responses to the foetal/maternal conflict.

PMID- 16969924
TI  - Bioethics and the law--the impact of genetic technology on prenatal management.

PMID- 16969925
TI  - Expanding access to treatment for HIV/HCV coinfected patients.

PMID- 16969926
TI  - Memorial to close global AIDS conference.

PMID- 16969927
TI  - HIV drugs. Doctors more concerned than patients about drug resistance.

PMID- 16969928
TI  - Housing. Dismissal granted in dispute over housing for AIDS clients.

PMID- 16969929
TI  - HIV and politics. Coalition launches AIDS-related voter education campaign.

PMID- 16969930
TI  - HIV-positive man's disability claim fails over lack of evidence.

PMID- 16969932
TI  - Medical center cleared of wrongful HIV disclosure.

PMID- 16969931
TI  - Dismissal upheld in HIV drug monopoly claim.

PMID- 16969933
TI  - Nation's capital implements new jail HIV testing.

PMID- 16969934
TI  - Dialectical behavior therapy for clients with HIV.

PMID- 16969935
TI  - End of an era.

PMID- 16969936
TI  - Monitoring the spread of bluetongue in northern Europe.

PMID- 16969937
TI  - Dating dispersal and radiation in the gymnosperm Gnetum (Gnetales)--clock
      calibration when outgroup relationships are uncertain.
AB  - Most implementations of molecular clocks require resolved topologies. However,
      one of the Bayesian relaxed clock approaches accepts input topologies that
      include polytomies. We explored the effects of resolved and polytomous input
      topologies in a rate-heterogeneous sequence data set for Gnetum, a member of the
      seed plant lineage Gnetales. Gnetum has 10 species in South America, 1 in
      tropical West Africa, and 20 to 25 in tropical Asia, and explanations for the
      ages of these disjunctions involve long-distance dispersal and/or the breakup of
      Gondwana. To resolve relationships within Gnetum, we sequenced most of its
      species for six loci from the chloroplast (rbcL, matK, and the trnT-trnF region),
      the nucleus (rITS/5.8S and the LEAFY gene second intron), and the mitochondrion
      (nad1 gene second intron). Because Gnetum has no fossil record, we relied on
      fossils from other Gnetales and from the seed plant lineages conifers, Ginkgo,
      cycads, and angiosperms to constrain a molecular clock and obtain absolute times
      for within-Gnetum divergence events. Relationships among Gnetales and the other
      seed plant lineages are still unresolved, and we therefore used differently
      resolved topologies, including one that contained a basal polytomy among
      gymnosperms. For a small set of Gnetales exemplars (n = 13) in which rbcL and
      matK satisfied the clock assumption, we also obtained time estimates from a
      strict clock, calibrated with one outgroup fossil. The changing hierarchical
      relationships among seed plants (and accordingly changing placements of distant
      fossils) resulted in small changes of within-Gnetum estimates because
      topologically closest constraints overrode more distant constraints. Regardless
      of the seed plant topology assumed, relaxed clock estimates suggest that the
      extant clades of Gnetum began diverging from each other during the Upper
      Oligocene. Strict clock estimates imply a mid-Miocene divergence. These
      estimates, together with the phylogeny for Gnetum from the six combined data
      sets, imply that the single African species of Gnetum is not a remnant of a once
      Gondwanan distribution. Miocene and Pliocene range expansions are inferred for
      the Asian subclades of Gnetum, which stem from an ancestor that arrived from
      Africa. These findings fit with seed dispersal by water in several species of
      Gnetum, morphological similarities among apparently young species, and incomplete
      concerted evolution in the nuclear ITS region.

PMID- 16969938
TI  - Incorporating allelic variation for reconstructing the evolutionary history of
      organisms from multiple genes: An example from Rosa in North America.
AB  - Allelic variation within individuals holds information regarding the
      relationships of organisms, which is expected to be particularly important for
      reconstructing the evolutionary history of closely related taxa. However, little
      effort has been committed to incorporate such information for reconstructing the
      phylogeny of organisms. Haplotype trees represent a solution when one
      nonrecombinant marker is considered, but there is no satisfying method when
      multiple genes are to be combined. In this paper, we propose an algorithm that
      converts a distance matrix of alleles to a distance matrix among organisms. This
      algorithm allows the incorporation of allelic variation for reconstructing the
      phylogeny of organisms from one or more genes. The method is applied to
      reconstruct the phylogeny of the seven native diploid species of Rosa sect.
      Cinnamomeae in North America. The glyceralgehyde 3-phosphate dehydrogenase
      (GAPDH), the triose phosphate isomerase (TPI), and the malate synthase (MS) genes
      were sequenced for 40 individuals from these species. The three genes had little
      genetic variation, and most species showed incomplete lineage sorting, suggesting
      these species have a recent origin. Despite these difficulties, the networks
      (NeighborNet) of organisms reconstructed from the matrix obtained with the
      algorithm recovered groups that more closely match taxonomic boundaries than did
      the haplotype trees. The combined network of individuals shows that species west
      of the Rocky Mountains, Rosa gymnocarpa and R. pisocarpa, form exclusive groups
      and that together they are distinct from eastern species. In the east, three
      groups were found to be exclusive: R. nitida-R. palustris, R. foliolosa, and R.
      blanda-R. woodsii. These groups are congruent with the morphology and the ecology
      of species. The method is also useful for representing hybrid individuals when
      the relationships are reconstructed using a phylogenetic network.

PMID- 16969939
TI  - Detecting the node-density artifact in phylogeny reconstruction.
AB  - The node-density effect is an artifact of phylogeny reconstruction that can cause
      branch lengths to be underestimated in areas of the tree with fewer taxa.
      Webster, Payne, and Pagel (2003, Science 301:478) introduced a statistical
      procedure (the "delta" test) to detect this artifact, and here we report the
      results of computer simulations that examine the test's performance. In a sample
      of 50,000 random data sets, we find that the delta test detects the artifact in
      94.4% of cases in which it is present. When the artifact is not present (n =
      10,000 simulated data sets) the test showed a type I error rate of approximately
      1.69%, incorrectly reporting the artifact in 169 data sets. Three measures of
      tree shape or "balance" failed to predict the size of the node-density effect.
      This may reflect the relative homogeneity of our randomly generated topologies,
      but emphasizes that nearly any topology can suffer from the artifact, the effect
      not being confined only to highly unevenly sampled or otherwise imbalanced trees.
      The ability to screen phylogenies for the node-density artifact is important for
      phylogenetic inference and for researchers using phylogenetic trees to infer
      evolutionary processes, including their use in molecular clock dating.

PMID- 16969940
TI  - Maximizing phylogenetic diversity in biodiversity conservation: Greedy solutions
      to the Noah's Ark problem.
AB  - The Noah's Ark Problem (NAP) is a comprehensive cost-effectiveness methodology
      for biodiversity conservation that was introduced by Weitzman (1998) and utilizes
      the phylogenetic tree containing the taxa of interest to assess biodiversity.
      Given a set of taxa, each of which has a particular survival probability that can
      be increased at some cost, the NAP seeks to allocate limited funds to conserving
      these taxa so that the future expected biodiversity is maximized. Finding optimal
      solutions using this framework is a computationally difficult problem to which a
      simple and efficient "greedy" algorithm has been proposed in the literature and
      applied to conservation problems. We show that, although algorithms of this type
      cannot produce optimal solutions for the general NAP, there are two restricted
      scenarios of the NAP for which a greedy algorithm is guaranteed to produce
      optimal solutions. The first scenario requires the taxa to have equal
      conservation cost; the second scenario requires an ultrametric tree. The NAP
      assumes a linear relationship between the funding allocated to conservation of a
      taxon and the increased survival probability of that taxon. This relationship is
      briefly investigated and one variation is suggested that can also be solved using
      a greedy algorithm.

PMID- 16969941
TI  - A geometric approach to tree shape statistics.
AB  - This article presents a new way to quantify the descriptive ability of tree shape
      statistics. Where before, tree shape statistics were chosen by their ability to
      distinguish between macroevolutionary models, the resolution presented in this
      paper quantifies the ability of a statistic to differentiate between similar and
      different trees. This is termed the geometric approach to differentiate it from
      the model-based approach previously explored. A distinct advantage of this
      perspective is that it allows evaluation of multiple tree shape statistics
      describing different aspects of tree shape. After developing the methodology, it
      is applied here to make specific recommendations for a suite of three statistics
      that may prove useful in applications. The article ends with an application of
      the statistics to clarify the impact of taxa omission on tree shape.

PMID- 16969942
TI  - Increasing data transparency and estimating phylogenetic uncertainty in
      supertrees: Approaches using nonparametric bootstrapping.
AB  - The estimation of ever larger phylogenies requires consideration of alternative
      inference strategies, including divide-and-conquer approaches that decompose the
      global inference problem to a set of smaller, more manageable component problems.
      A prominent locus of research in this area is the development of supertree
      methods, which estimate a composite tree by combining a set of partially
      overlapping component topologies. Although promising, the use of component tree
      topologies as the primary data dissociates supertrees from complexities within
      the underling character data and complicates the evaluation of phylogenetic
      uncertainty. We address these issues by exploring three approaches that variously
      incorporate nonparametric bootstrapping into a common supertree estimation
      algorithm (matrix representation with parsimony, although any algorithm might be
      used), including bootstrap-weighting, source-tree bootstrapping, and hierarchical
      bootstrapping. We illustrate these procedures by means of hypothetical and
      empirical examples. Our preliminary experiments suggest that these methods have
      the potential to improve the correspondence of supertree estimates to those
      derived from simultaneous analysis of the combined data and to allow uncertainty
      in supertree topologies to be quantified. The ability to increase the
      transparency of supertrees to the underlying character data has several practical
      implications and sheds new light on an old debate. These methods have been
      implemented in the freely available program, tREeBOOT.

PMID- 16969943
TI  - The effect of combining molecular and morphological data in published
      phylogenetic analyses.

PMID- 16969944
TI  - Which random processes describe the tree of life? A large-scale study of
      phylogenetic tree imbalance.

PMID- 16969945
TI  - -Omics dreams of personalized healthcare.

PMID- 16969946
TI  - Sample handling washes proteins away.

PMID- 16969947
TI  - Proteomics of starvation.

PMID- 16969948
TI  - Herbicides can alter crop proteomes.

PMID- 16969949
TI  - HUPO HLPP takes on a herculean task.

PMID- 16969950
TI  - TGN1412: the catalyst for change?

PMID- 16969951
TI  - Animal experimentation levels continue to rise.

PMID- 16969952
TI  - Puzzling intestinal uptake in 99mTc-DPD bone scintigraphy.

PMID- 16969954
TI  - Polio endemic countries hit all-time low of four.

PMID- 16969953
TI  - Focal pelvic uptake in 18F-FDG PET due to a contraceptive device; a potential
      pitfall easily unmasked by PET-CT.

PMID- 16969955
TI  - Global measles deaths plunge by 48% over past six years.

PMID- 16969956
TI  - Avian influenza.

PMID- 16969957
TI  - Privacy and policy for genetic research.
AB  - I begin with a discussion of the value of privacy and what we lose without it. I
      then turn to the difficulties of preserving privacy for genetic information and
      other medical records in the face of advanced information technology. I suggest
      three alternative public policy approaches to the problem of protecting
      individual privacy and also preserving databases for genetic research: (1)
      governmental guidelines and centralized databases, (2) corporate self-regulation,
      and (3) my hybrid approach. None of these are unproblematic; I discuss strengths
      and drawbacks of each, emphasizing the importance of protecting the privacy of
      sensitive medical and genetic information as well as letting information
      technology flourish to aid patient care, public health and scientific research.

PMID- 16969958
TI  - Genomic research and data-mining technology: implications for personal privacy
      and informed consent.
AB  - This essay examines issues involving personal privacy and informed consent that
      arise at the intersection of information and communication technology (ICT) and
      population genomics research. I begin by briefly examining the ethical, legal,
      and social implications (ELSI) program requirements that were established to
      guide researchers working on the Human Genome Project (HGP). Next I consider a
      case illustration involving deCODE Genetics, a privately owned genetic company in
      Iceland, which raises some ethical concerns that are not clearly addressed in the
      current ELSI guidelines. The deCODE case also illustrates some ways in which an
      ICT technique known as data mining has both aided and posed special challenges
      for researchers working in the field of population genomics. On the one hand,
      data-mining tools have greatly assisted researchers in mapping the human genome
      and in identifying certain "disease genes" common in specific populations (which,
      in turn, has accelerated the process of finding cures for diseases tha affect
      those populations). On the other hand, this technology has significantly
      threatened the privacy of research subjects participating in population genomics
      studies, who may, unwittingly, contribute to the construction of new groups
      (based on arbitrary and non-obvious patterns and statistical correlations) that
      put those subjects at risk for discrimination and stigmatization. In the final
      section of this paper I examine some ways in which the use of data mining in the
      context of population genomics research poses a critical challenge for the
      principle of informed consent, which traditionally has played a central role in
      protecting the privacy interests of research subjects participating in
      epidemiological studies.

PMID- 16969959
TI  - Property rights in genetic information.
AB  - The primary theme of this paper is the normative case against ownership of one's
      genetic information along with the source of that information (usually human
      tissues samples). The argument presented here against such "upstream" property
      rights is based primarily on utilitarian grounds. This issue has new salience
      thanks to the Human Genome Project and "bio-prospecting" initiatives based on the
      aggregation of genetic information, such as the one being managed by deCODE
      Genetics in Iceland. The rationale for ownership is twofold: ownership will
      protect the basic human rights of privacy and autonomy and it will enable the
      data subjects to share in the tangible benefits of the genetic research.
      Proponents of this viewpoint often cite the principle of genetic exceptionalism,
      which asserts that genetic information needs a higher level of protection than
      other kinds of personal information such as financial data. We argue, however,
      that the recognition of such ownership rights would lead to inefficiency along
      with the disutility of genetic discoveries. Biomedical research will be hampered
      if property rights in genes and genetic material are too extensive. We contend
      that other mechanisms such as informed consent and strict confidentiality rules
      can accomplish the same result as a property right without the liabilities of an
      exclusive entitlement.

PMID- 16969960
TI  - How the role of computing is driving new genetics' public policy.
AB  - In this paper we will examine some ethical aspects of the role that computers and
      computing increasingly play in new genetics. Our claim is that there is no new
      genetics without computer science. Computer science is important for the new
      genetics on two levels: (1) from a theoretical perspective, and (2) from the
      point of view of geneticists practice. With respect to (1), the new genetics is
      fully impregnate with concepts that are basic for computer science. Regarding
      (2), recent developments in the Human Genome Project (HGP) have shown that
      computers shape the practices of molecular genetics; an important example is the
      Shotgun Method's contribution to accelerating the mapping of the human genome. A
      new challenge to the HGP is provided by the Open Source Philosophy (I computer
      science), which is another way computer technologies now influence the shaping of
      public policy debates involving genomics.

PMID- 16969961
TI  - Beware! Uncle Sam has your DNA: legal fallout from its use and misuse in the U.S.
AB  - Technology has provided state and federal governments with huge collections of
      DNA samples and identifying profiles stored in databanks. That information can be
      used to solve crimes by matching samples from convicted felons to unsolved
      crimes, and has aided law enforcement in investigating and convicting suspects,
      and exonerating innocent felons, even after lengthy incarceration. Rights
      surrounding the provision of DNA samples, however, remain unclear in light of the
      constitutional guarantee against "unreasonable searches and seizures" and privacy
      concerns. The courts have just begun to consider this issue, and have provided
      little guidance. It is unclear whether the laws governing protected health
      information are applicable to the instant situation, and if so, the degree to
      which they apply. DNA databanks are not uniformly regulated, and it is possible
      that DNA samples contained in them may be used for purposes unintended by donors
      of the samples. As people live their lives, they leave bits of their DNA behind.
      They cannot be assured that these tiny specimens will not be taken or used
      against their will or without their knowledge for activities such as profiling to
      measure tendencies such as thrill-seeking, aggressiveness, or crimes with
      threatening behavior. Existing racial or ethnic discrimination and profiling may
      also encompass genetic discrimination and profiling, creating societal class
      distinctions. This article will explore the constitutionality of collecting
      genetic materials, the ethics of such activities, and balance the social good in
      solving crime and deterrence against the individual's security, liberty, and
      privacy.

PMID- 16969962
TI  - An integrative curriculum: science by design.

PMID- 16969963
TI  - The mitochondrial genome, aging and neurodegenerative disorders.

PMID- 16969964
TI  - Effects of caloric restriction on gene expression.

PMID- 16969965
TI  - Early life effects on aging.

PMID- 16969966
TI  - Impaired regulation of energy intake in old age.

PMID- 16969967
TI  - Aging and body composition.

PMID- 16969968
TI  - Insulin resistance: a genetic approach. Overview.

PMID- 16969969
TI  - Functional changes in the gastrointestinal system.

PMID- 16969970
TI  - The impact of nutrition on bone health: new concepts.

PMID- 16969971
TI  - Nutrition and cognition in older persons.

PMID- 16969972
TI  - Known related effects of nutrition on aging muscle function.

PMID- 16969973
TI  - Exercise, sarcopenia, cognition, and mood.

PMID- 16969974
TI  - The 2001 assessment of nutritional influences on risk of cataract.

PMID- 16969975
TI  - Age-related changes in hydration.

PMID- 16969976
TI  - Nutrition and the aging immune response.

PMID- 16969977
TI  - Physical assessment for aging prediction.

PMID- 16969978
TI  - Rationale for tests of the neuropsychiatric effects of nutrient deficiency.

PMID- 16969979
TI  - Targeting renal cell carcinoma.

PMID- 16969980
TI  - Interstitial low dose rate brachytherapy for prostate cancer--a focus on
      intermediate- and high-risk disease.
AB  - AIMS: To investigate the role of brachytherapy in intermediate- and high-risk
      prostate cancer. We report our results and a review of published studies.
      MATERIALS AND METHODS: Between March 1999 and April 2003, 300 patients were
      treated with low dose rate 1-125 interstitial prostate brachytherapy and followed
      prospectively. The patients were stratified into low-, intermediate- and high
      risk groups and received brachytherapy alone or in combination with external beam
      radiotherapy (EBRT) and/or neoadjuvant androgen deprivation (NAAD). One hundred
      and forty-six patients were classified as low risk, 111 as intermediate risk and
      43 as high risk. Biochemical freedom from disease and prostate-specific antigen
      (PSA) nadirs were analysed for risk groups and for treatment received in each
      risk group. RESULTS: The median follow-up was 45 months (range 33-82 months) with
      a mean age of 63 years. Actuarial 5-year biochemical relapse-free survival for
      the low-risk group was 96%, 89% for the intermediate-risk group and 93% for the
      high-risk group. When stratified by treatment group, low-risk patients had a 5
      year actuarial biochemical relapse-free survival of 94% for brachytherapy alone
      (n=77), 92% for NAAD and brachytherapy (n=66) and 100% for NAAD, EBRT and
      brachytherapy (n=3). In the intermediate-risk patients, biochemical relapse-free
      survival was 93% for brachytherapy alone (n=15), 94% for NAAD and brachytherapy
      (n=67), 75% for EBRT and brachytherapy (n=4) and 92% for NAAD, EBRT and
      brachytherapy (n=25). In the high-risk group, biochemical relapse-free survival
      was 100% for brachytherapy alone (n=2), 88% for NAAD and brachytherapy (n=7), 80%
      for EBRT and brachytherapy (n=5) and 96% for NAAD, EBRT and brachytherapy (n=29).
      Overall 3- and 4-year PSA = 0.5 ng/ml were achieved by 71 and 86%, respectively,
      and a 4-year PSA = 0.2 ng/ml was achieved by 63%. CONCLUSION: Although the role
      of combination treatment with pelvic EBRT and androgen therapy is not clear, our
      early results show that many patients with intermediate- and high-risk disease
      have excellent results with brachytherapy.

PMID- 16969981
TI  - Exploratory analysis of the bacteriological status of post-irradiation wounds and
      its relationship to healing.
AB  - AIMS: To investigate the bacteriological status of post-irradiation wounds and
      its relationship to wound healing in patients with nasopharyngeal cancer.
      MATERIALS AND METHODS: One hundred and forty-six nasopharyngeal cancer patients
      with post-irradiation wounds on one or both sides of the neck were studied
      prospectively. Swabs were taken from the wounds at the initial study visit for
      bacteriological examination. A further swab for culture was taken when possible
      signs of infection developed. Wound healing was assessed on alternate days with
      respect to wound condition, the presence of clinical infection and healing time.
      RESULTS: The results showed that most of the post-irradiation wounds were
      colonised with bacteria. This was not associated with clinical signs of infection
      in any instance. There was no association between wound healing time and the
      presence of organisms, the identity of organisms, the number of species of
      organisms, or the use of antibiotics. CONCLUSIONS: The presence of bacteria in
      post-irradiation wounds, in the absence of clinical signs of wound infection, is
      not a barrier to wound healing. Oncology practitioners should recognise the
      unique features of radiation-induced wounds and skin reactions with confidence
      and provide appropriate treatment as needed.

PMID- 16969982
TI  - Radiosensitivity, radiogenomics and RAPPER.

PMID- 16969983
TI  - Assessing the difference between planned and delivered intensity-modulated
      radiotherapy dose distributions based on radiobiological measures.
AB  - AIMS: Because of the highly conformal distributions that can be obtained with
      intensity-modulated radiotherapy (IMRT), any discrepancy between the intended and
      delivered distributions would probably affect the clinical outcome. Consequently,
      there is a need for a measure that would quantify those differences in terms of a
      change in the expected clinical outcome. MATERIALS AND METHODS: To evaluate such
      a measure, cancer of the cervix was used, where the bladder and rectum are
      proximal and partially overlapping with the internal target volume. A solid
      phantom simulating the pelvic anatomy was fabricated and a treatment plan was
      developed to deliver the prescribed dose to the phantom. The phantom was then
      irradiated with films positioned in several transverse planes. The racetrack
      microtron at 50 MV was used in the treatment planning and delivery processes. The
      dose distribution delivered was analysed based on the film measurements and
      compared against the treatment plan. The differences in the measurements were
      evaluated using both physical and biological criteria. Whereas the physical
      comparison of dose distributions can assess the geometric accuracy of delivery,
      it does not reflect the clinical effect of any measured dose discrepancies.
      RESULTS: It is shown how small inaccuracies in delivered dose can affect the
      treatment outcome in terms of complication-free tumour cure. CONCLUSIONS: With
      highly conformal IMRT, the accuracy of the patient set-up and treatment delivery
      are critical for the success of the treatment. A method is proposed to evaluate
      the precision of the delivered plan based on changes in complication and control
      rates as they relate to uncertainties in dose delivery.

PMID- 16969984
TI  - Palliative radiotherapy improves pain and reduces functional interference in
      patients with painful bone metastases: a quality assurance study.
AB  - AIMS: To characterise the effect of palliative radiotherapy treatment outcomes as
      evaluated by the Brief Pain Inventory within a radiotherapy clinic, as a quality
      assurance initiative. MATERIALS AND METHODS: Tumour and treatment parameters of
      patients with painful bone metastases treated through a dedicated bone pain
      radiotherapy clinic have been prospectively recorded since 2002. One hundred and
      nine ambulatory patients provided pre- and post-treatment pain assessments at 4-6
      weeks after palliative radiotherapy. The self-administered Brief Pain Inventory
      questionnaire was completed by patients during their visits. Changes in pain and
      seven-item functional interference scores were analysed. RESULTS: Most of the
      patients had prostate (n=42) or breast (n=42) cancer. The mean Karnofsky
      performance score was 70 before palliative radiation therapy. Sixty-eight per
      cent of patients were treated with a single fraction (6-8 Gy) and 25% received 20
      Gy/five fractions. The overall response (reduction in worst pain by > or = 2/10)
      was 72%. Sixty-one per cent of patients had stable or reduced consumption of
      opioid analgesics. A significant reduction for all seven functional interference
      items was seen after treatment, the greatest improvement being general activity (
      2.4/10). There was significant correlation between pain reduction and improvement
      in functional interference. CONCLUSION: This quality assurance initiative showed
      that palliative radiotherapy reduced both pain and its interference on function
      among ambulatory patients with symptomatic bone metastases. The reduction in pain
      was correlated with reductions in functional interference. Clinical trials of
      palliative radiotherapy should provide data that allow an evaluation of various
      domains of chronic pain.

PMID- 16969985
TI  - Serious ocular complications of zoledronate.

PMID- 16969986
TI  - Preparing for the first day of the rest of your life. How should we train
      clinical oncology consultants?

PMID- 16969987
TI  - What is valuable for specialist registrars to learn in order to become good
      consultant clinical oncologists?
AB  - AIMS: Given the pressures for change in training, it is important that what is
      valuable for specialist registrars to learn in order to become good consultant
      clinical oncologists is identified to aid in curricular design. MATERIALS AND
      METHODS: A qualitative, one-to-one, semi-structured interview study was
      undertaken with 12 clinical oncologists who had been appointed as consultants
      within the last 2 years. RESULTS: They described the 'shock' on realising that
      they had entered foreign territory. The three main themes that emerged were
      surviving, navigating and moving forward. CONCLUSIONS: It was not enough to be a
      competent clinician. The newly appointed consultant could only carry out their
      clinical work adequately and develop as clinicians, researchers and educators if
      they could navigate the maze of emotions, relationships and management structures
      contained in the clinical and organisational contexts of their work.

PMID- 16969988
TI  - Functional imaging in clinical oncology: magnetic resonance imaging- and
      computerised tomography-based techniques.
AB  - Over recent years, advances in cellular biology, molecular biology and genetics
      have led to a leap forward in our understanding of the biological basis of
      cancer. Some of these developments have revealed processes and targets that can
      be visualised and measured by new functional imaging techniques. The resulting
      images have the potential to improve cancer staging, prognosis and risk
      assessment, guide radiotherapy planning, direct treatment schedules, improve
      response assessment and provide new end points for clinical trials. In this
      review, we have outlined the magnetic resonance imaging- and computerised
      tomography-based functional techniques and provide evidence for their use.

PMID- 16969989
TI  - Laparoscopic feeding jejunostomy during neo-adjuvant chemotherapy for
      oesophagogastric cancer.

PMID- 16969990
TI  - Male cancer patients' attitudes towards female health professionals during
      urological consultations.

PMID- 16969991
TI  - Lymphangitis carcinomatosis as a potential predictor for a response to gefitinib.

PMID- 16969992
TI  - Hepatocellular carcinoma presenting as multifocal haemorrhagic encephalitis.

PMID- 16969993
TI  - Bilateral avascular necrosis of the hips after chemoradiotherapy for cervical
      cancer.

PMID- 16969994
TI  - Automated high-performance liquid chromatography detection of serum retinol
      levels in cervical cancer patients compared with normal subjects.

PMID- 16969995
TI  - Comment on: Mathematical modelling of survival of glioblastoma patients suggests
      a role for radiotherapy dose escalation and predicts poorer outcome after delay
      to start treatment (Burnet et al. Clin Oncol 2006;18:93-103).

PMID- 16969996
TI  - Health promoting settings: future directions.

PMID- 16969997
TI  - The statement of the global consortium on community health promotion.

PMID- 16969998
TI  - Preffi 2.0- a quality assessment tool.
AB  - The findings of many meta-studies into the effects of health promotion programmes
      indicate that there is still much room for improvement in the quality of these
      programmes. Insights gained from research are rarely applied in practice.
      Practitioners and policymakers often find it hard to assess the value of the many
      and sometimes contradictory research findings, partly because the necessary
      contextual information is usually lacking. Practical considerations force them to
      respond to specific problems at short notice in the form of programmes that are
      as effective as possible. Hence, effective health promotion requires not only the
      dissemination of effective programmes but also insights into principles of
      effectiveness and the way professionals use these insights. It is against this
      background that the Netherlands Institute for Health Promotion and Disease
      Prevention (NIGZ) has developed and implemented the Preffi instrument. Preffi
      consists of a set of guidelines with items relevant to the effectiveness of
      health promotion and prevention projects, reflecting scientific and practical
      knowledge about effect predictors. This article describes the systematic, seven
      step development process of the second version of the instrument, Preffi 2.0, a
      process in which scientists and practitioners were closely involved throughout.
      The article also describes the Preffi model and its scoring method. The draft
      version of Preffi 2.0 was tested for usefulness among 35 experienced
      practitioners from a range of health promotion institutes. They were asked to use
      the draft version to assess two project descriptions and to comment on their
      experiences using Preffi 2.0. They gave the instrument an average overall mark of
      7.7 on a scale of 10, and the large majority of them evaluated the instrument as
      valuable, complete, clear, well-organised and innovative. The findings of this
      trial implementation were used to construct the definitive version of Preffi 2.0.
      To an experienced user, applying Preffi to assess a project takes less than an
      hour. Preffi is used as a diagnostic quality assurance instrument at various
      stages of a project, either to critically evaluate one's own project or to
      comment on projects proposed by others. Assessing other people's projects may be
      difficult if the necessary information is lacking or unclear. A supplementary
      discussion with the project manager is always required. Users have commented that
      applying Preffi to a project yields a balanced and useful assessment, as well as
      a clear overview of points in the project that could be improved.

PMID- 16969999
TI  - Cultural and western influences on the nutrition transition in Thailand.
AB  - The impact of economic development and urbanisation on nutrition and dietary
      changes in transitional countries has been well researched. It generally has been
      found that there is a positive correlation between economic development,
      urbanization, and negative nutrition transitions with the result of growing
      levels of obesity and diet related non-communicable diseases. However, the impact
      of Western influences and culture on specific eating styles associated with the
      nutrition transition has been less studied. There is limited information about
      cultural and Western influences on eating styles in Thailand. Recent findings
      suggest that Thailand may have progressed further along the nutrition transition
      model, in terms of unhealthy eating styles, than would be expected based on
      economic development. This study was designed to determine the prevalence of
      current eating styles and eating motivations among Thai university students.
      University students were chosen for evaluation as they are thought to represent
      the forefront of dietary trends and nutrition changes in a population.
      Convenience samples from four different universities in south-central and
      northern Thailand were selected. The following scales were used to assess eating
      and dieting styles and attitudes among 662 Thai undergraduate and graduate
      students: Motivation For Eating Scale (MFES), Eating Attitudes Test-26 (EAT-26),
      and Cognitive Dieting Behavior Scale (CBDS). All scales have been shown to be
      reliable and valid in previous research. For this study, scales were translated
      into Thai, reverse translated, and pilot tested to ensure cultural relevancy and
      the conveyance of intended meanings. Basic demographic information was also
      obtained, including age, gender, year in school, marital status, height and
      weight, and income. Results indicated that Thai students exhibit significant
      levels of dieting behaviour and extrinsic eating based on CBDS and MFES scores
      (with the exception of environmental eating). For most negative eating styles,
      females scored higher than males. It was also found that high levels of dieting
      and extrinsic eating were positively correlated with body mass index, suggesting
      the possible risk of future weight gain and obesity. While the occurrence of
      eating disordered attitudes based on EAT-26 scores was low (13%), analysis of EAT
      26 scores indicated that the occurrence of eating disordered attitudes was
      strongly correlated with dieting behaviour among this population. The results
      support the need for a programme to educate Thai students, especially females,
      regarding healthy patterns of dieting and eating attitudes in order to prevent
      future weight gains and eating disorders predicted by the nutrition transition
      model.

PMID- 16970000
TI  - Health promotion policies in the Republic of Korea and Japan: a comparative
      study.
AB  - Health promotion strategies have been developed and implemented in some Asian
      countries, particularly in the Republic of Korea (Korea) and Japan. It would help
      to understand features of health promotion in each country to compare health
      promotion strategies between them. In this study, using categories developed by
      HP-Source.net, we conducted a comparative analysis of health promotion strategies
      between Korea and Japan to understand features of health promotion in each
      country and contribute to the improvement of population health. One of the goals
      of Health Plan 2010 is to assess its achievements with numerical targets, which
      is also the case in Japan. One of the important discussion points involves a
      decision on the optimal number of targets for evaluation. There is a major
      difference in the funding of health promotion activities between Korea and Japan.
      They are financed through the general account in Japan, while in Korea a
      foundation for health promotion has been established and the income from tobacco
      tax is ring-fenced for this fund. The database and methodology of HP-Source needs
      adaptation for global use. We encountered some disadvantages in using its current
      framework for comparing and analysing information on health promotion in Korea
      and Japan. It has been recognised that HP-Source could influence the development
      and implementation of health promotion strategies in other parts of the world.
      Health promotion tools can help decision makers, planners and researchers to
      formulate and enhance comprehensive plans. In this study we learned many lessons
      in expanding policy tools outside of one region to aid the global development of
      effective health promotion policy and practice.

PMID- 16970001
TI  - The use of "sin taxes" to fund heath promotion foundations: introducing the
      debate addressed in Karen Slama's article.

PMID- 16970002
TI  - Background information for adopting a policy encouraging earmarked tobacco and
      alcohol taxes for the creation of health promotion foundations.

PMID- 16970003
TI  - 'We don't want to manage poverty': community groups politicise food insecurity
      and charitable food donations.
AB  - Charitable assistance is a common response to food insecurity in many affluent
      countries. The coalition featured in this case study is explicitly concerned with
      social justice, mitigating the potential for charitable assistance to mask the
      extent of food insecurity, its root causes and its long-term consequences. The
      coalition structure has assisted community workers in transcending day-to-day
      routines, so as to reflect on the politics of food insecurity and
      institutionalised responses to this problem. Coalition members have defined food
      security as an objective whose achievement will entail comprehensive reform. One
      noteworthy outcome has been to recommend that member groups not redistribute a
      number of foodstuffs commonly donated by individuals and corporations. In
      grappling with a tension between responding to immediate needs for food and
      addressing the root causes of these needs, community workers have paid attention
      to public health.

PMID- 16970004
TI  - Women's health resources: facilitating a community of care for midlife women.
AB  - Since 1981 research has explored the role of women's health centres in providing
      health information and education to women in a non-traditional setting. These
      settings have been designed to provide more appropriate, and often more
      comprehensive, care by responding to the specific health issues and needs of
      women across the age continuum. The type of care and resources provided by these
      centres make a significant contribution to women's capacity for participation in
      decisions and action around their own, health. This article examines the service
      delivery and perceived roles of one such centre, the Women's Health Resources
      (WHR) centre in Calgary, Canada. Data for this paper were extracted from WHR
      evaluation forms for 199 midlife women seeking individual consultation, as well
      as personal interviews that were conducted with four female staff members.
      Clients of the WHR cited numerous reasons for seeking service at the centre, the
      most common being for emotional health care, nutritional consultation or more
      comprehensive information on a specific illness. Three major components of
      service provision at the centre were identified: information, psychological care
      and complementarity of services. Women used the information they gained from WHR
      services to aid in health decision-making and as a resource for empowerment in
      being partners in their own health. Clients noted that the WHR was a valuable
      source of additional information beyond what their own family physician and/or
      specialist were able to provide. The feminist and woman-centred care at WHR, in
      conjunction with the emphasis on education, offers an invaluable source of
      information and services for women. Through the shared experiences of both the
      clients and staff of this centre, this article provides an outline of how such
      services are perceived and utilized.

PMID- 16970005
TI  - [Acute renal failure following NSAID use in 2 children with subclinical
      dehydration].
AB  - A 13,5-year-old girl was seen a few days after she had taken an overdose of
      NSAIDs and a 12,5-year-old girl presented with continuous epigastric pain with
      radiation to the left side for the past 3 days, a subfebrile temperature, loss of
      appetite and nausea without vomiting after she had taken an NSAID a few times
      following a painful accident. Laboratory tests showed that both girls were
      dehydrated, even though this was not visible on physical examination. Fractional
      sodium excretion was below 1%. Predisposing factors for the dehydration were
      little fluid intake during the previous days, heavy menstruation in one patient
      and perhaps purging or laxative abuse in the other. The renal function recovered
      after rehydration. In these patients, subclinical dehydration was sufficient to
      cause nephrotoxicity. Because of an increased risk of dehydration, paracetamol is
      preferred for the treatment of fever and/or pain in children.

PMID- 16970006
TI  - [Comparable results with percutaneous transluminal angioplasty and surgical
      bypass for critical ischaemia of the leg].
AB  - In patients with critical limb ischaemia resulting from arterial occlusion, both
      percutaneous recanalisation and bypass surgery are potential therapeutic options
      to avoid amputation. The recently published Bypass versus angioplasty in severe
      ischaemia of the leg (BASIL) trial is the first randomised study to compare these
      techniques. The data from this trial show that patients eligible for balloon
      angioplasty or infra-inguinal bypass surgery fare equally well with percutaneous
      intervention. In the Netherlands, expertise with percutaneous intervention varies
      among hospitals. Consequently, the preferred strategy depends on the capabilities
      of the local hospital. Ideally, patients should be treated in hospitals with
      expertise in both techniques, because there is a trend towards fewer
      complications with percutaneous intervention. Moreover, there is a considerable
      difference in costs during the first year in favour of percutaneous intervention,
      mainly as a result of a shorter hospital stay.

PMID- 16970007
TI  - [Gastroenteropancreatic neuroendocrine tumours (carcinoid tumours): definition,
      clinical aspects, diagnosis and therapy].
AB  - Carcinoid tumours are rare neuroendocrine tumours. In 2000 the WHO developed a
      new classification which gives a better description of the characteristics and
      biological behaviour of the tumour. Their advised designation is
      gastroenteropancreatic neuroendocrine tumour (GEP-NET). Somatostatin receptor
      scintigraphy has the highest sensitivity for visualisation of GEP-NETs. In the
      recent past years new positron emission tomography (PET) tracers have been
      developed and PET scanning is likely to become an important tool in the near
      future. Surgical resection is the treatment of first choice for a patient with a
      GEP-NET. In metastatic disease a number of forms ofpalliative treatment are
      possible. Cytotoxic chemotherapy seems only to be effective in aggressive, poorly
      differentiated tumours. Therapy with somatostatin analogues leads to objective
      tumour regression in a minority of patients only. New advances in peptide
      receptor radionuclide therapy using radioactive-labelled somatostatin analoga are
      showing better results.

PMID- 16970008
TI  - [Initiatives to increase the efficiency of dermatological patient care].
AB  - The number of tasks required of dermatologists has increased in the last decade.
      This article discusses potential ways to enhance the efficiency ofdermatological
      patient care and prevent problems of capacity. A study conducted in the UK found
      that, for the top 10 skin disorders, the accessibility of general practitioners
      with special expertise in dermatology was better than that of the dermatology
      clinic. Waiting times were considerably shorter with the general practitioners,
      but care was more expensive. Outcomes were similar for these skin disorders in
      terms of disease-specific quality of life. The study made no comment on the
      actual diagnostic ability of the specialised general practitioners.
      Teledermatology can reduce the number of referrals to a dermatologist by half.
      However, a considerable percentage of teledermatological consultations result in
      a different diagnosis than that obtained during a standard 'in vivo'
      consultation. Teledermatology can be a useful option for the follow-up of
      patients with ulcus cruris. The efficiency of dermatological care can be
      increased by working in teams. Dermatological nurses can be trained and conduct
      their own consultations under the supervision of a dermatologist. Dermatological
      care can also be organised in regional cooperative groups with general
      practitioners. Within these groups, teledermatology and specialised dermatology
      training for general practitioners can be useful innovations.

PMID- 16970009
TI  - [Guideline 'Diagnosis and treatment of oesophageal carcinoma'].
AB  - An evidence-based guideline for the diagnosis and treatment of oesophageal
      carcinoma was developed on the initiative of the Netherlands Society of
      Gastroenterohepatology in cooperation with the Dutch Institute for Healthcare
      Improvement (CBO) and the Dutch Association of Comprehensive Cancer Centres. If a
      patient with oesophageal carcinoma is eligible for treatment with curative
      intent, they should undergo thoracic and abdominal CT, ultrasound investigation
      of the supraclavicular region and endoscopic ultrasonography for staging
      purposes. Endoscopic therapy is the preferred treatment for high-grade dysplasia
      or early cancer in Barrett's oesophagus confined to the mucosa. Surgical
      resection is indicated if the tumour invades the submucosa. If resection of the
      oesophageal carcinoma is performed with curative intent, one should aim for
      radical resection. The type and extent of the resection depends on the location
      of the tumour. There is evidence that the mortality rate following surgery can be
      reduced by performing it in centres with ample experience with oesophageal cancer
      surgery. Preoperative chemotherapy and radiotherapy may improve survival in
      patients with oesophageal carcinoma. Palliative treatment for oesophageal
      carcinoma should be considered in cases of local invasion of surrounding organs,
      metastases, poor physical condition of the patient or recurrent disease after
      previous curative treatment. Psychosocial support is an important element in the
      follow-up of patients with oesophageal carcinoma.

PMID- 16970010
TI  - [Diagnostic image (288). A woman with lower right abdominal pain].
AB  - A woman with lower right abdominal pain was diagnosed with a nail perforating the
      appendix. She must have swallowed this nail in infancy.

PMID- 16970011
TI  - [The Dutch MRSA policy should be retained].
AB  - The Dutch methicillin-resistant Staphylococcus aureus (MRSA) 'search and destroy'
      policy is effective. MRSA should be banned from hospitals: MRSA infections are
      associated with increased mortality and costs. In addition, widespread use of
      vancomycin for treating MRSA infections encourages the spread and development of
      vancomycin-resistant micro-organisms.

PMID- 16970012
TI  - [The current MRSA policy in the Netherlands is doing more harm than good].
AB  - The current policy concerning methicillin-resistant Staphylococcus aureus (MRSA)
      in hospitals needs to be altered because there is no reliable proof that the
      isolation policy that is currently in force actually leads to any reduction in
      the prevalence of MRSA. Conversely, it has been proved that these isolation
      measures lead to poorer patient care, sometimes resulting in death.

PMID- 16970013
TI  - [Menstruation disorders more frequent in women with a history of sexual abuse].
AB  - OBJECTIVE: To determine the relationship between menstruation disorders and prior
      sexual abuse. DESIGN: Questionnaire investigation. METHOD: A questionnaire was
      developed consisting of 50 questions about menstruation disorders, premenstrual
      syndrome and sexual abuse. The questionnaire was mailed to all female patients
      aged 12-54 years (n = 1805) of one family practice in Den Helder, the
      Netherlands. RESULTS: The response rate to the questionnaire was 69% (n = 1254).
      After excluding women who were postmenopausal, pregnant, without a uterus, or who
      did not answer the questions on sexual abuse, 947 remained. Of these women, 83
      (8.7%) reported having experienced sexual abuse. These women had significantly
      more dysmenorrhoea, more dysfunctional menstrual bleeding and significantly more
      menstrual cycle irregularities. CONCLUSION: A statistically significant
      association was found between menstrual problems and prior sexual abuse. Sexual
      abuse should be considered in the differential diagnosis and treatment of women
      who seek medical help for inexplicable menstrual disorders.

PMID- 16970014
TI  - [Myositis as a 'radiation-recall phenomenon' following palliative chemotherapy
      with carboplatin-gemcitabin for non-small-cell pulmonary carcinoma].
AB  - A 58-year-old woman suffered pain due to a stage-IV adenocarcinoma of the right
      upper-lung lobe with signs of growth into the right axilla. Palliative local
      radiotherapy directed at the primary tumour followed by combination chemotherapy
      with carboplatin-gemcitabin led to partial remission. During the fourth and last
      cycle of her three-months course of chemotherapy, the patient again complained of
      pain in the right half of the thorax; later, a local swelling of the pectoralis
      muscles was found. She was diagnosed with myositis as a delayed reaction to
      irradiation (radiation-recall phenomenon) based on the clinical symptoms (redness
      of the skin, pain and distinct swelling) but especially on the basis of a CT
      scan. This revealed a clear swelling of the pectoralis muscles, even though the
      tumour was in remission. The possibility of myositis as a radiation-recall
      phenomenon should be borne in mind whenever a patient presents with skin changes
      or pain within a previous irradiation field during chemotherapy with, for
      example, gemcitabin.

PMID- 16970015
TI  - [Massive haemolysis: a rare manifestation of sepsis due to Clostridium
      perfringens].
AB  - A 59-year-old man was admitted to the hospital to be operated on for carcinoma of
      the pancreas. During the operation, it turned out that resection ofthe tumour was
      not possible. Therefore, a double bypass was created for palliation:
      hepaticojejunostomy and duodenojejunostomy. The postoperative course was
      complicated by a fulminant sepsis accompanied by massive intravascular
      haemolysis. This is a rare and often fatal complication of a Clostridium
      perfringens sepsis. The patient was given antibiotics and multiple blood
      transfusions, but his haemoglobin remained low and despite the administration of
      large amounts of fluid, high doses ofinotropic agents and corticosteroids, it was
      not possible to achieve an adequate circulation. The patient died within 40 hours
      after admission to Intensive Care. Severe intravascular haemolysis with
      spherocytes in the blood smear must be interpreted as an important indication of
      a C. perfringens-sepsis.

PMID- 16970016
TI  - [Acne vulgaris: endocrine aspects].

PMID- 16970017
TI  - Defining and treating constipation in older adults.

PMID- 16970018
TI  - Cholinesterase inhibitors for Alzheimer's disease.

PMID- 16970019
TI  - Cirrhosis and chronic liver failure: part I. Diagnosis and evaluation.
AB  - Cirrhosis and chronic liver failure are leading causes of morbidity and mortality
      in the United States, with the majority of preventable cases attributed to
      excessive alcohol consumption, viral hepatitis, or nonalcoholic fatty liver
      disease. Cirrhosis often is an indolent disease; most patients remain
      asymptomatic until the occurrence of decompensation, characterized by ascites,
      spontaneous bacterial peritonitis, hepatic encephalopathy, or variceal bleeding
      from portal hypertension. Physical examination of patients with cirrhosis may
      reveal a variety of findings that necessitate a hepatic- or gastrointestinal
      based work-up to determine the etiology. Some patients already may have had
      laboratory or radiographic tests that incidentally uncovered signs of cirrhosis
      and its comorbidities. No serologic or radiographic test can accurately diagnose
      cirrhosis. A significant correlation has been demonstrated between persistently
      elevated liver function tests and biopsy-proven underlying hepatic disease; thus,
      a more targeted serologic work-up is indicated in patients whose liver function
      test results are persistently abnormal. Unnecessary medications and surgical
      procedures should be avoided in patients with cirrhosis. Referral for liver
      biopsy should be considered only after a thorough, non-invasive serologic and
      radiographic evaluation has failed to confirm a diagnosis of cirrhosis; the
      benefit of biopsy outweighs the risk; and it is postulated that biopsy will have
      a favorable impact on the treatment of chronic liver disease.

PMID- 16970020
TI  - Cirrhosis and chronic liver failure: part II. Complications and treatment.
AB  - Major complications of cirrhosis include ascites, spontaneous bacterial
      peritonitis, hepatic encephalopathy, portal hypertension, variceal bleeding, and
      hepatorenal syndrome. Diagnostic studies on ascitic fluid should include a
      differential leukocyte count, total protein level, a serum-ascites albumin
      gradient, and fluid cultures. Therapy consists of sodium restriction, diuretics,
      and complete abstention from alcohol. Patients with ascitic fluid
      polymorphonuclear leukocyte counts of 250 cells per mm3 or greater should receive
      empiric prophylaxis against spontaneous bacterial peritonitis with cefotaxime and
      albumin. Patients who survive an episode of spontaneous bacterial peritonitis
      should receive long-term prophylaxis with norfloxacin or
      trimethoprim/sulfamethoxazole. Patients with gastrointestinal hemorrhage and
      cirrhosis should receive norfloxacin or trimethoprim/sulfamethoxazole twice daily
      for seven days. Treatment of hepatic encephalopathy is directed toward improving
      mental status levels with lactulose; protein restriction is no longer
      recommended. Patients with cirrhosis and evidence of gastrointestinal bleeding
      should undergo upper endoscopy to evaluate for varices. Endoscopic banding is the
      standard treatment, but sclerotherapy with vasoconstrictors (e.g., octreotide)
      also may be used. Prophylaxis with propranolol is recommended in patients with
      cirrhosis once varices have been identified. Transjugular intrahepatic
      portosystemic shunt has been effective in reducing portal hypertension and
      improving symptoms of hepatorenal syndrome, and can reduce gastrointestinal
      bleeding in patients with refractory variceal hemorrhage. When medical therapy
      for treatment of cirrhosis has failed, liver transplantation should be
      considered. Survival rates in transplant recipients have improved as a result of
      advances in immunosuppression and proper risk stratification using the Model for
      End-Stage Liver Disease and Child-Turcotte-Pugh scoring systems.

PMID- 16970021
TI  - Information from your family doctor. Cirrhosis and chronic liver failure: what
      you should know.

PMID- 16970022
TI  - Avian influenza: preparing for a pandemic.
AB  - Avian influenza A (H5N1) first emerged as a global public health threat in 1997
      when it caused a major human outbreak in Hong Kong. Endemic in waterfowl and
      highly virulent in poultry, H5N1 is capable of incidentally infecting humans and
      other mammals. Although H5N1 is not yet capable of efficient human-to-human
      transmission, the protean nature of its genome could transform it into the source
      of the next human influenza pandemic. In the spring of 2006, migrating birds
      spread the virus from Asia to Europe and Africa. Preparing for a new influenza
      pandemic involves increasing global influenza surveillance and developing
      practical strategies for containing outbreaks at the source. Prompt case
      recognition, isolation, and treatment will be crucial for disease control.
      Pharmacologic interventions will focus on streamlining the production of vaccine,
      extending vaccine supplies, stockpiling antiviral drugs such as oseltamivir, and
      distributing these agents in a timely manner to persons who have the most need.
      Nonpharmacologic measures will include the use of masks, social distancing,
      quarantine, travel restrictions, and increasing the emergency capacity of health
      care systems.

PMID- 16970023
TI  - Promoting medication adherence in children.
AB  - The problem of getting children to follow a treatment regimen is widespread and
      is frustrating for physicians. The extent to which any patient adheres to a
      medical regimen is an essential determinant of clinical success. Strategies to
      improve adherence in children include using simplified drug regimens (e.g., once
      daily dosing), pleasant-tasting medicines, liquid or other nonpill formulations,
      regular phone contact between parents and physicians, reminders, information
      counseling, self-management plans, and other forms of individualized supervision
      or attention. Physicians also can encourage adherence by providing a dearly
      written explanation or patient information sheets that list generic and brand
      names, dosage, schedule, duration, and common side effects and practical ways of
      coping with them. Physicians, children, and parents should develop a mutually
      agreed-upon treatment plan. Having the child participate in devising the plan
      improves adherence.

PMID- 16970024
TI  - Information from your family doctor. Getting your child to take medicine.

PMID- 16970025
TI  - Acute low back pain.

PMID- 16970026
TI  - Asymptomatic yellowish papules.

PMID- 16970027
TI  - Information from your family doctor. Melanoma: A type of skin cancer.

PMID- 16970028
TI  - Information from your family doctor. Saving your skin from sun damage.

PMID- 16970029
TI  - Information from your family doctor. Checking yourself for signs of skin cancer.

PMID- 16970030
TI  - Obesity: psychological and behavioral considerations.

PMID- 16970031
TI  - Ectrodactyly, ectodermal dysplasia, macular degeneration syndrome: a further
      contribution.
AB  - EEM syndrome is a rare condition characterised by ectodermal dysplasia,
      ectrodactyly and macular dystrophy. Additional abnormalities such as alopecia,
      cataract, absent eyebrows, and oligodontia may occur. We report two brothers and
      a sister born to consanguineous parents with EEM syndrome. EEM syndrome differs
      from other ectrodactly syndromes by the characteristic findings in the ocular
      fundus showing extensive retinochoroidal atrophy with diffuse retinal
      pigmentation and mild arteriolar attenuation at the posterior pole. In contrast
      to other ectrodactyly syndromes autosomal recessive inheritance is most likely.

PMID- 16970032
TI  - Constitutional duplication 11q23 de novo involving the MLL gene.
AB  - We report a child with mental retardation, brain anomalies and congenital heart
      defect. His karyotype, after G-banding and FISH with a whole chromosome probe for
      chromosome 11 and a locus-specific probe for the MLL gene, was
      46,XY,dup(11)(q23q23).ish dup(11)(q23q23)(wcp11+, MLL++) de novo; i.e., he had a
      pure partial 11q23 duplication. Clinical and cytogenetic findings of the present
      case were compared with the 7 previously reported cases with pure partial trisomy
      11q; in 6/8 cases the region 11q23 was involved. We conclude that the scarce
      number of cases and their heterogeneity do not allow to establish a reliable
      genotype-phenotype correlation.

PMID- 16970034
TI  - Otocephaly, and pulmonary malformation association: two case reports.
AB  - Otocephaly is a rare lethal malformation of the first and second branchial
      arches. We report two infants with otocephaly and failed resuscitation. Both
      infants had pulmonary malformations: pulmonary hypoplasia and two-lobed right
      lung. We report these rare associations with a brief review of the literature.

PMID- 16970033
TI  - A new syndrome with prenatally diagnosed thoracoschisis, hiatal hernia and
      extremities' agenesis: case report.
AB  - Thoracoschisis is a very rare congenital anomaly and is usually associated with
      limb and abdominal wall defects forming part of limb-body wall complex. We here
      present a case of a 29-week-4-day pregnancy ended with intrauterine demise.
      Postmortem examination revealed hiatal hernia, thoracoschisis and protrusion of
      some part of liver from this defect, left forearm agenesis and right arm and
      right hand agenesis. The findings accompanying thoracoschisis in this presented
      case exclude any previously reported related syndrome and we believe that this is
      a new syndrome.

PMID- 16970035
TI  - A case of trisomy 12 mosaicism with pituitary malformation and polycystic ovary
      syndrome.
AB  - We report the case of a patient (followed from birth to 15 years) presenting with
      trisomy 12 mosaicism, and focus on the endocrine phenotype associating a
      pituitary malformation and ovarian abnormalities. We describe the dysmorphic
      features and their evolution, the growth retardation and ovarian symptoms.
      Complete growth hormone deficiency was confirmed on auxological data, stimulation
      test and was related to pituitary stalk interruption, diagnosed by magnetic
      resonance imaging. Effect of growth hormone treatment was satisfactory resulting
      in a normal adult height. She also presented premature thelarche associated with
      right ovarian hypertrophy (4 to 5 fold the volume of the left ovary) which
      remained constant until 15 years of age. Diagnosis of trisomy 12 mosaicism was
      made on skin and ovarian karyotypes. The possible relation between these endocine
      findings and some genes located on chromosome 12 involved in pituitary and
      ovarian development is discussed.

PMID- 16970036
TI  - Direct transmission of the 18q- syndrome from mother to daughter.
AB  - A 34-year-old mother presented moderate mental retardation, short stature,
      microcephaly, and characteristic facial dysmorphism. Her 12-year-old daughter
      manifested moderate mental retardation, short stature, microcephaly, dysplastic
      external ear canals, hearing impairment, and characteristic facial dysmorphism.
      Cytogenetic analysis of the family revealed a normal karyotype, 46,XY, in the
      father, and a 46,XX,del(18)(q22.2) karyotype in both mother and daughter.
      Molecular marker analysis determined direct transmission of the distal 18q
      deletion from mother to daughter. The present case provides evidence of fertility
      of the affected females and a mother-to-daughter direct transmission in the
      familial 18q- syndrome. Identification of affected females with the 18q- syndrome
      should include genetic counseling of possible direct transmission and
      consideration of birth control or prenatal genetic testing at reproductive age.

PMID- 16970037
TI  - Heterogeneity of the triple A syndrome and assessment of a case.
AB  - Allgrove syndrome (triple A syndrome) is a rare autosomal recessive disorder
      characterized by achalasia, alacrima, adrenal insufficiency, and--occasionally-
      autonomic instability. Disease causing mutations have been found in the AAAS gene
      on 12q13, but no strong phenotype-genotype correlation could be found. We present
      a 28 year-old woman with classical systemic features of triple A syndrome with
      prominent neurological dysfunctions/deficits, including distal muscular atrophy,
      progressive muscle weakness and wasting of both legs, sensibility dysfunction,
      hyperreflexia and autonomic dysfunction presented with excessive sweating. DNA
      sequencing of the AAAS gene revealed compound heterozygosity for previously
      reported mutations. A similar genotype was previously reported, but with a
      remarkably different phenotype.

PMID- 16970038
TI  - A case with mosaic partial duplication of 1q: prenatal and postmortem clinical
      and cytogenetic evaluations.
AB  - Partial trisomy 1q including different segments of the long arm is a rare
      cytogenetic anomaly. Especially the cases with mosaic proximal tandem duplication
      of 1q included a longer fragment are very rare. Cases who have partial 1q trisomy
      showed large phenotypic variation due to the differences in size of the
      duplicated segments of 1q. The clinical phenotype of most cases is characterized
      by multiple congenital anomalies especially including central nervous system and
      developmental delay. We describe a prenatally diagnosed case with mild cerebral
      ventriculomegaly and karyotype with mosaic pure trisomy of chromosome 1q
      [(46,XX/46,XX,dup(1)(q21qter)]. Phenotypic postmortem examination showed cranial
      asymmetry, flat and broad nasal bridge, anteverted nostrils, hypertelorism,
      retrognathia, abnormal pinnae, hypoplasic thumbs, long fingers and toes,
      mediodorsal curvature of the 4th and 5th toes and posterior prominence of the
      heel was observed. Autopsy confirmed the ventriculomegaly. Postmortem chromosome
      preparation from skin culture, cord blood and intracardiac blood confirmed the
      mosaic pure trisomy of chromosome 1q.

PMID- 16970039
TI  - Mosaicism for terminal deletion of 4q.
AB  - Chromosomal imbalance affecting the long arm of chromosome 4 has been reported in
      a variety of distinct clinical conditions. Common clinical findings have been
      described for 4q deletions distal to 4q33 and termed as 4q terminal deletion
      syndrome. We report two children with de novo chromosomal abnormality consisting
      of a terminal deletion (q33qter) of chromosome 4 in mosaic form. The phenotypes
      of these two patients are very similar to that described in the literature, but
      milder because of the mosaic nature of cytogenetic abnormality.

PMID- 16970040
TI  - Partial trisomy of long arm of chromosome 4 as a result of dir dup (4)(q27q31.3)
      de novo.
AB  - The phenotype of a girl at age of 12 years with a partial trisomy 4q caused by
      unique direct duplication 4q27 --> q31.3 included the thick, broad and straight
      eyebrows, upward slanting palpebral fissures, a deep-set eyes, narrow bridge and
      long back of the nose, flattened philtrum columns, narrow of vermilion borders of
      both upper and lower lips, protrusion of maxillary alveolar processus and
      anterior teeth together with shortened and posteriorly situated mandible,
      malocclusion corresponding with II class of Angle and long fingers, narrowing
      towards distal phalanges has been described. Further investigations are needed to
      delineate the clinical spectrum of features essential for partial trisomy 4q.

PMID- 16970041
TI  - Cytogenetic results of amniocentesis materials: incidence of abnormal karyotypes
      in the Turkish collaborative study.
AB  - The experience on prenatal chromosome diagnosis of four Turkish centers
      participating in a collaborative study on 6041 genetic amniocentesis performed
      during a 4-8 years period were reviewed. 5887 (97.5%) patients had strong
      clinical indications for prenatal chromosome studies and 154 (2.5%) were referred
      because of maternal anxiety and a bad history of previous gestations. The main
      indication groups were: advanced maternal age (3197 cases), positive serum
      screening (2011 cases), ultrasound-identified anomaly (492 cases), previous
      fetus/child with chromosomal aberrations (103 cases), a history of a previous
      abnormal and/or mentally handicapped child (70 cases) and a parental chromosome
      rearrangement (14 cases). The average maternal age was 33.9 years and average
      gestational age was 18 weeks. A total of 179 affected fetuses were detected in
      this collaborative study (3%) of which 133 were unbalanced (74.3%). Among the 124
      (69%) numerical aberrations, 102 (82.3%) were autosomal aneuploidies, 20 (16.1%)
      were gonosomal aneuploidies and 2 (1.6%) were poliploidies. Among the 55 (31%)
      structural aberrations, balanced translocation was the most common (63.6%) and 11
      cases of inversion, four cases of unbalanced translocation, two cases of marker
      chromosome and three cases of other abnormalities were found. The overall culture
      success rate was 99.7%. Pregnancy termination that is permitted by legal
      authorities was accepted by 94.7% (126/133) with parents at unbalanced
      cytogenetic result announcement.

PMID- 16970042
TI  - An infant with diaphragmatic hernia, anophthalmia and cardiac defect: evaluation
      by magnetic resonance imaging autopsy.
AB  - We present an infant with diaphragmatic hernia, anophthalmia and cardiac defect
      evaluated by magnetic resonance imaging (MRI) autopsy. This female infant was
      born at 39th weeks by vaginal delivery and presented with diaphragmatic hernia,
      anophthalmia, cardiac defect and died due to respiratory problems at 28th hours
      of life. MRI autopsy showed internal organ abnormalities including congenital
      hernia of the left diaphragm, secondary hypoplasia of the left lung, atrial and
      ventricular septal defect, dilatation of calices of the kidneys, bilateral
      anophthalmia, hypoplasia of the optic nerves, hyperintensity of pituitary gland
      possibly due to bleeding and a cyst of the septum pellucidum. This article shows
      that MRI autopsy is a valuable method for the evaluation of cases with congenital
      anomalies if autopsy is not possible.

PMID- 16970043
TI  - The strange association between achondroplasia and neurofibromatosis type 1:
      molecular analysis of a new patient and review of the literature.
AB  - The association between Achondroplasia and Neurofibromatosis type 1 has been
      described in only three patients. We report the clinical features and molecular
      characterization of a new patient with de novo ACH and NF1, providing for the
      first time a detailed clinical and molecular evaluation. Even if this association
      seems coincidental, some startling, intriguing correlations are discussed at the
      clinical and molecular level, between ACH, NF, and the existence of a common
      "mutator" genotype.

PMID- 16970044
TI  - Dandy-Walker malformation in mosaic Klinefelter syndrome.

PMID- 16970045
TI  - Lethal multiple pterigium syndrome: genetic counseling.

PMID- 16970046
TI  - Dandy-Walker syndrome with postaxial polydactyly associated with facial
      dysmorphism and bone abnormalities.

PMID- 16970047
TI  - Dietary glycaemic index: a review of the physiological mechanisms and observed
      health impacts.

PMID- 16970048
TI  - Relationship of left ventricular mass to insulin sensitivity and body mass index
      in healthy individuals.
AB  - OBJECTIVE: The objective of this study was to investigate the contribution of
      insulin resistance, hyperinsulinaemia and obesity, independently of other major
      factors, to changes in left ventricular mass a cardiovascular risk indicator, in
      a healthy population without co-morbid states such as diabetes or hypertension.
      METHODS AND RESULTS: This cross-sectional relational study was perfomed in 153
      healthy subjects, comprising 76 men and 77 women with ages ranging from 23 to 67
      years. All of them were normotensive and had a normal oral glucose tolerance
      test, none had cardiovascular disease and none were taking any medication.
      Weight, height and waist circumference were measured and BMI was calculated. A
      blood sample was drawn in the fasting state: plasma glucose, insulin, serum total
      and high density lipoprotein (HDL), low density lipoprotein cholesterol and
      triglycerides were measured. Insulin resistance was determined by the
      'Homeostasis Assessment Model' (HOMA-IR). Subjects were studied by
      echocardiography. The left ventricular mass was calculated by using the
      anatomically validated formula of Devereux et al. RESULTS: Left ventricular mass
      significantly and positively correlated with BMI, age, systolic and diastolic
      blood pressure and fasting blood glucose. The correlation of left ventricular
      mass with fasting blood glucose was not maintained after controlling for BMI.
      BMI, fasting blood glucose, HOMA-IR, systolic and diastolic blood pressure showed
      significant differences with higher values for people with left ventricular
      hypertrophy. The logistic regression analysis showed a strong association between
      left ventricular hypertrophy and BMI (p < 0.05). CONCLUSION: Insulin resistance
      and fasting insulin is not associated with left ventricular hypertrophy in
      healthy people, independent of obesity. Obesity appears to be an independent risk
      factor for left ventricular hypertrophy.

PMID- 16970049
TI  - Use of the Internet by parents of children with congenital heart disease.
AB  - OBJECTIVE: We sought to document the prevalence of Internet access and usage
      patterns among families with children diagnosed with congenital heart disease.
      MATERIAL AND METHODS: A questionnaire was administered to the parents of 509
      unselected children with congenital heart disease attending the outpatient
      cardiac clinic. RESULTS: 389 questionnaires were completed. The most common
      source for acquiring medical information was via the paediatric cardiologist
      (83%), the family doctor (53%), the general paediatrician (40%) and the Internet
      (15%). Among the 238 families with Internet access (62%), the most common
      locations for Internet access were home (74%) and work (33%), and 84 used the
      Internet to obtain information related to their child's cardiac diagnosis, mostly
      at the time of diagnosis. Two-thirds of these families considered finding
      information related to the cardiac diagnosis as easy or very easy, and found this
      information helpful or very helpful. CONCLUSION: A quarter of the families uses
      the Internet to find information about their child's congenital heart disease.
      Internet use in this patient population is expected to increase and our vigilance
      in providing accurate references and in identifying inaccurate information is of
      paramount importance.

PMID- 16970050
TI  - Effects of non-heavy smoking on high-density lipoprotein cholesterol in healthy
      Turkish young men.
AB  - OBJECTIVE: Decreased effects of smoking on serum high-density lipoprotein
      cholesterol (HDL-c) were demonstrated in subjects smoking more than 20 cigarettes
      a day. We aimed to evaluate the effects of non-heavy smoking (< or =20 cigarettes
      a day) on HDL-c in young, healthy men who are similar in terms of age, physical
      activity and diet. METHODS: A total of 1012 male students between 19 and 25 years
      old (21.4 +/- 1.5) in a military college who do not smoke or smoking < or =20
      cigarettes a day were enrolled. Subjects who were consuming alcohol were
      excluded. Smoking levels (0: nonsmoker, 1: 1-5 cigarettes, 2: 6-10 cigarettes,
      3:11-20 cigarettes a day) and duration were obtained by a questionnaire. Blood
      samples were taken after an over-night fasting. Blood pressure and anthropometric
      measurements were reported. RESULTS: HDL-c showed a stepwise decrease as the
      level of smoking increased (49 +/- 9 mg/dL in level 0, 47 +/- 7 mg/dL in level 1,
      46 +/- 8 mg/dL in level 2, 45 +/- 7 mg/dL in level 3, p < 0.001). Total
      cholesterol, triglycerides and low-density cholesterol were not different among
      the smoking levels. Body mass index (BMI) and waist/hip ratio were found to be
      slightly decreased in smokers. In a multivariate regression model including
      smoking level, duration, BMI, systolic and diastolic blood pressures, smoking
      level was the only predictor of HDL-c (B = -1.407, p < 0.001). CONCLUSION:
      Smoking, even in relatively low levels, has a negative stepwise relationship with
      HDL-c in a homogeneous population of healthy young men in whom other major non
      genetic factors that are known to affect HDL-c levels are identical.

PMID- 16970051
TI  - Influence of diurnal blood pressure rhythm on aortic elastic properties in
      hypertensive subjects.
AB  - OBJECTIVE: The aim of this study was to evaluate whether there is a relationship
      between aortic elastic properties and diurnal blood pressure rhythm in
      hypertensive subjects. METHODS AND RESULTS: This study included 41 hypertensive
      patients who were taking medical treatment and had undergone ambulatory blood
      pressure monitoring (ABPM). The patients were classified according to their night
      mean systolic blood pressure (Nm-SBP) fall. On the basis of Nm-SBP fall: 10
      (24.4%) patients were dippers (with 10% but < 20% fall), 19 (46.3%) patients were
      nondippers (with 0% but <0% fall) and 12 (29.3%) patients were reverse dippers
      (with <0%). All subjects underwent echocardiographic examination. Internal aortic
      root diameters were measured at 3 cm above the aortic valve by the use of two
      dimensional guided M-mode transthoracic echocardiography, and arterial blood
      pressure was measured simultaneously from the brachial artery by
      sphygmomanometry. Two indexes of the aortic elastic properties were measured
      which are aortic distensibility and aortic stiffness index. After subgroup
      analysis of the hypertensive patients, the highest aortic stiffness index value
      was found in reverse dipper patients (5.8 +/- 3.4) followed by nondipper patients
      (4.87 +/- 3.5) and the lowest in dipper patients (3.5 +/- 1.3) although clinical
      blood pressure values of hypertensive patients were similar. The aortic stiffness
      index value of reverse dippers and nondippers (5.6 +/- 3.4) was higher than in
      the (3.5 +/- 1.3) dippers group. CONCLUSION: In this study, we found a relation
      between diurnal blood pressure patterns and aortic elastic properties.

PMID- 16970052
TI  - Pulse wave velocity in patients with coronary artery disease or type 2 diabetes
      mellitus.
AB  - OBJECTIVE: To check whether the presence of coronary artery disease (CAD) or type
      2 diabetes mellitus (DM) has a differentiating effect on arterial stiffness
      assessed with pulse wave velocity (PWV)--a simple, reproducible and clinically
      feasible measure of arterial stiffening. METHODS AND RESULTS: The mean age of 101
      participants was 63.5 +/- 19.7 years. Fifty-one % of them had CAD, 31.0% had DM
      and 52.5% were hypertensive subjects. The aortic PWV ranged from 3.40 to 27.50
      m/s, with an average of 1.73 +/- 4.69 m/s. PWV was significantly higher (P <
      0.01) in both CAD and DM positive groups as compared with CAD and DM negatives,
      respectively. After adjustment for established co-variables, patients with CAD
      had significantly higher PWV when compared to CAD negatives (13.0 vs. 10.5 m/s, P
      < 0.01). After adjustment, DM did not seem to affect PWV. CONCLUSIONS: CAD
      patients had higher values of PWV when compared to those without the disease. DM,
      a metabolic equivalent of arterial damage, after adjustment for possible
      confounders, did not seem to contribute per se to arterial stiffening. The
      presence of high PWV values in that group of patients should be viewed as an
      indicator of established widespread atherosclerosis possibly affecting the
      coronary arteries.

PMID- 16970053
TI  - Could missile attacks trigger acute myocardial infarction?
AB  - OBJECTIVE: During the Gulf war in 2003, Kuwait was targeted with missile attacks
      for 10 consecutive days. Our objective is to evaluate the influence of missile
      attacks on the incidence of acute myocardial infarction (AMI). METHODS AND
      RESULTS: We retrospectively compared the number of admissions for AMI presenting
      to a major general hospital during missile attacks period (MAP) in 2003 with four
      control periods. MAP and each control period consisted of the same number of days
      (10 days). The four control periods were the 10 days immediately before and after
      MAP; and the same time period as MAP for the years 2001 and 2002. The number of
      admissions for AMI was highest during MAP, 21 cases compared to 14-16 cases in
      the four control periods, with a trend towards increase during MAP (incidence
      rate ratio = 1.59; 95% CI 0.95 to 2.66, p < 0.07). The number of admissions for
      AMI during the first 5 days of MAP was significantly higher compared to the first
      5 days of the four control periods (incidence rate ratio = 2.43; 95% CI 1.23 to
      4.26, p < 0.01). The observed AMI admission rate during the first 5 days of MAP
      was significantly higher than expected for a 5-day period in the years 2001, 2002
      and 2003. This increase was specific to AMI and did not affect other acute
      cardiac conditions. CONCLUSIONS: Missile attacks were associated with an increase
      in the incidence of AMI. This increase was specific to AMI and did not influence
      acute cardiac conditions.

PMID- 16970054
TI  - Increased plasma homocysteine and allantoin levels in coronary artery disease:
      possible link between homocysteine and uric acid oxidation.
AB  - OBJECTIVE: Homocysteine increases the damage to the cardiovascular system in
      different ways, one of them is the formation of reactive oxygen species resulting
      from the auto-oxidation of homocysteine. At the same time, uric acid is one of
      the major antioxidants in the plasma and protects the cells towards increased ROS
      activity. In humans, allantoin is only formed from non-enzymatic oxidation of
      uric acid by free radicals. We aimed to determine the levels of homocysteine,
      uric acid and allontoin in patients with coronary artery diseases, and to
      evaluate the possible correlation between homocysteine and allantoin. METHODS AND
      RESULTS: Plasma total homocysteine, uric acid and allantoin levels of 50 patients
      with coronary artery diseases and 23 healthy controls were determined by HPLC
      methods. Commercial diagnostic kits were used for the determination of other
      biochemical parameters. We obtained higher homocysteine, uric acid and allantoin
      levels in patients than in controls (p < 0.0001). Homocysteine levels were
      positively correlated with uric acid (r = 0.435, p < 0.0001) and allantoin (r =
      0.583, p < 0.0001) levels in the whole study population. This correlation was
      persistent between allantoin and homocysteine after adjustment of these
      parameters for age, sex and creatinine. We accepted 15.0 micromol/l as a cut-off
      value between normal and mildly elevated homocysteine levels for patients and
      controls. Twenty-five patients showed moderate hyperhomocysteinaemia. The mean
      allantoin and uric acid values of the moderate hyperhomocysteinaemic group were
      significantly higher than that of the group having lower homocysteine levels than
      this cut-off value (p < 0.0001 for allantoin, p < 0.02 for uric acid).
      CONCLUSION: Results imply that there is increased allantoin production resulting
      from uric acid oxidation by free radicals in hyperhomocysteinaemic patients with
      coronary artery disease. The possible significance of the relationship between
      homocysteine and allantoin warrants further study.

PMID- 16970055
TI  - Lipid profile of women qualifying for hypolipidaemic treatment.
AB  - OBJECTIVE: Death rates from coronary heart disease continue to rise in women
      despite a marked decrease in men for the past two decades. Our study aimed to
      evaluate essential risk factors in high-risk adult women. METHODS: Lipid profiles
      of 547 dyslipidaemic adult women aged 57.5 +/- 10.6 years (mean +/- standard
      deviation) were evaluated and stratified according to fasting plasma lipid
      levels. Classification of the cohort was performed based on triglycerides (TG)
      and high-density lipoprotein cholesterol (HDL-C) levels and correlations between
      TG and HDL-C were estimated. RESULTS: Patients with TG > or =150 mg/dl had lower
      HDL-C levels compared to those with TG <150 mg/dl (p < 0.001). Patients with HDL
      C <40 mg/dl had lower TC levels and higher TG levels compared to those with HDL-C
      > or =40 mg/dl (p = 0.012 and p < 0.001, respectively). In the cohort and the
      subgroups an inverse correlation between TG and HDL-C was observed (r = -0.428,
      slope = -0.048, p < 0.001). CONCLUSIONS: The expected inverse correlation between
      fasting high TG and low HDL levels was confirmed. The novelty of the study is
      that this correlation persists even in the case of low fasting TG levels.

PMID- 16970056
TI  - Evaluation of electrocardiographic algorithms in the assessment of the infarct
      related artery in acute myocardial infarction.
AB  - OBJECTIVES: In acute myocardial infarction, it is of great value to identify the
      infarct-related artery and the site of occlusion in a coronary artery (proximal
      versus distal). This study assessed the diagnostic value of two previously
      published electrocardiographic algorithms to identify the infarct-related artery
      and the site of occlusion in anterior and inferior acute myocardial infarction.
      METHODS AND RESULTS: We studied retrospectively a group of 88 patients with a
      first myocardial infarction. We determined the infarct-related artery using the
      electrocardiographic algorithms on the electrocardiogram at the time of admission
      and compared these results with the angiographically determined infarct-related
      artery. The best electrocardiographic algorithm could determine the infarct
      related artery in an inferior myocardial infarction as the left circumflex
      coronary artery and as the proximal and distal right coronary artery with a
      sensitivity of 63%, 67% and 80%, respectively, and a specificity of 100%, 82% and
      69%, respectively. One algorithm was unable to diagnose a left circumflex
      coronary artery occlusion. In an anterior myocardial infarction the best
      electrocardiographic algorithm could determine the infarct-related artery as the
      proximal and distal left anterior descending coronary artery with a sensitivity
      of 85% and 80%, respectively, and with a specificity of 77% and 82%,
      respectively. CONCLUSION: In acute myocardial infarction the use of
      electrocardiographic algorithms is helpful to predict the site of occlusion and
      can play a crucial role in the care of patients.

PMID- 16970057
TI  - Non-invasive methods in differentiating ischaemic from non-ischaemic
      cardiomyopathy. A review paper.
AB  - Chronic heart failure is a common disorder associated with high mortality and
      morbidity. Patients' numbers and the burden placed on health care services
      increase as the average age of the population rises. Non-invasive imaging plays a
      central role in the correct diagnosis of heart failure, the determination of
      aetiology and prognosis, as well as the monitoring of ongoing therapy. In this
      review paper we critically summarize techniques that differentiate ischaemic from
      non-ischaemic cardiomyopathy. Coronary angiography has been used as the primary
      method for distinguishing ischaemic from non-ischaemic cardiomyopathy; while
      studies utilizing echocardiography, myocardial perfusion imaging or electron
      computed tomography and positron emission tomography, have played a substantial
      role. More recently, CMR and multislice computed tomography have demonstrated
      ability in initial functional assessment and in the determination of secondary
      causes of heart failure.

PMID- 16970058
TI  - Innervation of the atrioventricular and semi-lunar heart valves: a review.
AB  - Heart valves were historically considered passive structures that function
      through the haemodynamic forces created by the contraction and relaxation of the
      myocardium. However, research into valvular structures has revealed that heart
      valves are very complex, specialized structures that contain both smooth muscle
      cells and nerve fibres. This is particularly true for the atrioventricular
      valves, which are by far the most well studied to date. The various heart valves
      have been shown to contract independently during different moments of the heart
      cycle, suggesting that compensatory adaptation mechanisms exist to mediate the
      timing and efficacy of heart valve closure. These adaptations occur via different
      mechanisms, including neural mechanisms that influence the heart valves.
      Accumulating evidence continues to improve our understanding of the nerve fibres
      in the heart (adrenergic, cholinergic, etc.). Future studies will no doubt add to
      this exciting picture. Here, we review the current morphological knowledge of
      human and animal heart valve innervation, including discussions of the chordae
      tendineae and the papillary muscles, as well as the differences between the
      atrioventricular (AV) valves and the semi-lunar (SL) valves.

PMID- 16970059
TI  - Contrast echocardiography of right atrial mass due to hepatocellular carcinoma.
AB  - We describe one patient suffering from hepatocellular carcinoma who presented
      with a right atrial metastatic tumour as a result of invasion of the inferior
      vena cava and extension into the right atrium. Two-dimensional echocardiography
      disclosed the right atrium tumour and SonoVue contrast agent echocardiography was
      employed to assess the local extension of the mass and to exclude an important
      obstruction due to a mass in the right ventricular inflow. Surgical management in
      the presence of metastatic right atrial tumour thrombus is described in the
      literature with poor results and this type of treatment should be reserved only
      for selected cases in which acute and severe cardiovascular distress due to
      obstruction of right ventricular inflow is present.

PMID- 16970060
TI  - Duchenne's cardiomyopathy: two case reports.
AB  - We describe two cases of Duchenne's cardiomyopathy with severe cardiac
      dysfunction, sporadic episodes of myoglobinuria induced by effort and increased
      levels of serum creatine kinase. Very mild signs of skeletal myopathy were
      clinically evident. Left ventriculography showed diffuse severe hypokinesia.
      Skeletal muscle biopsy demonstrated a dystrophic process. The patients had no
      familial background of the disease. These 2 patients might have a sporadic
      inheritance pattern with severe cardiac involvement.

PMID- 16970061
TI  - Monomorphic and propafenone-induced polymorphic ventricular tachycardia in
      Brugada syndrome: a case report.
AB  - A 24-year-old man without structural heart disease was admitted following
      recurrent syncopes. His baseline ECG revealed a right bundle-branch block (RBBB)
      pattern. Spontaneous monomorphic and polymorphic ventricular tachycardias (VT)
      were observed during monitoring. The provocation test by propafenone brought out
      recurrent spontaneous polymorphic VT and provocation by ajmaline caused an ST
      elevation in V2. Programmed ventricular stimulation test during the
      electrophysiologic study revealed both monomorphic and polymorphic VT. The
      patient received an internal cardioverter/defibrillator with the diagnosis of
      Brugada syndrome.

PMID- 16970062
TI  - Regression of left ventricular hypertrophy during antihypertensive treatment.
AB  - Left ventricular hypertrophy is a risk factor for cardiovascular events and
      stroke. It has been demonstrated that the regression of left ventricular
      hypertrophy (evaluated by 12-lead electrocardiography and by echocardiography)
      during antihypertensive treatment is associated with a lower risk of
      cardiovascular mortality and may thus improve the prognosis. Black people run a
      disproportionately high risk of developing essential arterial hypertension which
      frequently results in end organ damage, including left ventricular hypertrophy,
      haemorrhagic stroke and renal failure. We report a case of significant regression
      of left ventricular hypertrophy in a sub-Saharan African patient, during
      antihypertensive treatment.

PMID- 16970063
TI  - Lipomatous hypertrophy of the interatrial septum.

PMID- 16970064
TI  - [Unusual metastasis of renal carcinoma].
AB  - Renal carcinoma, the third most common urological cancer, induces presence of
      metastases in 75% of cases. The most affected sites for metastasis are the lungs,
      the lymphatic system, bones, the liver, adrenal glands and the brain with
      sometimes a cancer free period of several years prior to evolutionary recurrence
      of the disease. The aim of this literature review is to report on secondary
      uncommon renal localizations by underlining their clinical significance, as well
      as main characteristics, in order to provide guidelines for effective patient
      diagnosis and therapeutic management.

PMID- 16970065
TI  - [Trauma to the anterior urethra: diagnosis and management].
AB  - Injuries to anterior urethra are uncommon, mainly due to blunt trauma, and rarely
      associated with pelvic fractures or life threatening multiple lesions. Straddle
      type injury is the most frequent lesion, in which the immobile bulbar urethra is
      crushed or compressed on the inferior surface to the pubic symphysis. Diagnosis
      of urethral injury is easy, suspected due to trauma circumstances, presence of
      urethrorragy or initial hematuria, and eventually difficult micturition and
      penile scrotal for perineoscrotal hematoma. It should always be confirmed and
      classified by retrograde urethro-gram, realized either immediately or after a few
      days. Initial acute management is suprapubic cystostomy, if possible before any
      attempt of urethral catheterization or miction. Urethral contusions only require
      this urinary diversion or urethral catheter for a few days and usually heal
      without any sequelae. Management of partial and complete disruptions remains
      controversial: suprapubic diversion only and secondary endoscopic or open
      surgical repair of the urethral stricture that occurs in the great majority of
      the cases (always after complete disruption), early endoscopic realignment and
      prolonged urethral catheterization (4 for 8 weeks according to the lesion), in
      partial disruptions, more controversial in complete disruptions; delayed (after a
      few days) open surgical repair (urethrorraphy) that is the preferred European and
      French attitude for complete disruptions. Penetrating anterior urethral trauma
      and urethral lesions associated with penile fracture require immediate surgical
      exploration and repair if possible. After anterior urethral disruption, the main
      morbidity is urethral stricture very often requiring surgical treatment (visual
      urethrotomy if the structure is short, end to end spatulated urethrorraphy, flap
      or graft urethroplasty if longer).

PMID- 16970066
TI  - [Conformal radiotherapy of prostate cancer].
AB  - A number of retrospective and prospective studies have demonstrated that
      radiotherapy of prostate cancer must be actually conformal. Three-dimensional
      (3D) treatment planning consists in an as accurate as possible definition of
      target-volume, usually by CT-scan, and design of radiation fields shaped to this
      target-volume. Several steps are required, each step being important for the
      overall quality of the treatment. Conformal radiotherapy is better tolerated than
      conventional irradiation, with significantly less rectal toxicity. It allows dose
      escalation up to 80 Gy. It is now possible to go beyond this dose with intensity
      modulated radiotherapy. The benefit of these high doses was demonstrated by some
      large retrospective studies and some prospective dose-escalation trials. Several
      randomized trials are in progress, preliminary results of two of them have been
      published, both showing an improvement in disease control with the higher doses.
      The advantage of higher doses is clearly evident for patients in the intermediate
      prognostic group, but is still discussed for patients with a low risk tumour or
      treated in combination with hormone therapy. Late proctitis is the main toxicity
      of these high doses. Some volume constraints have been defined during the last
      years and will allow a decrease of the rate of rectal toxicity. Because of these
      technological improvements, results of radiation therapy are now similar to those
      of surgery: no direct comparison with a randomized trial is available, but large
      comparative studies show that long-term disease control are identical with both
      techniques. Radiation therapy must be proposed to all patients with a prostate
      carcinoma as an alternative to surgery.

PMID- 16970067
TI  - [Should double J catheter be systematically considered in renal
      transplantation?].
AB  - Protection of urinary anastomoses using a ureteral catheter is a frequent option
      in urology but such use in a systematic manner remains debated in renal
      transplantation. Some consider that systematic insertion of a double J sound
      decreases the incidence of ureteral complications (fistula and stenosis). Others
      who prefer a selective use in some situations with a related risk consider that
      the implementation of a double J catheter cannot compensate a technical defect.
      It is even responsible for specific complications (infections, incrustation,
      haemorrhages); it increases implantation costs and is useless in more than 90% of
      the cases. This article analyses the risks related to systematic implementation
      of a double J catheter in Lich-Gregoir ureterovesical anastomoses for renal
      transplantation, together with the related costs and the infectious risk. The
      benefits in terms of prevention of ureteral complications are evaluated.

PMID- 16970068
TI  - [Urethrovesical anastomosis in retropubic radical prostatectomy].
AB  - Urethrovesical anastomosis is the most codified step in radical prostatectomy.
      Most of the time, the bladder neck diameter makes it possible to carry out a
      congruent anastomosis. Otherwise one has to resort either to the tennis racket
      closure or the parachute technique. Stenosis will remain an exceptional
      complication if the technique is applied with strictness and precision.

PMID- 16970069
TI  - [Endoscopic treatment of urethral strictures].
AB  - The present article reviews the literature regarding the endoscopic treatment of
      urethral strictures. Only few prospective randomised clinical trials with
      sufficient power have been performed and most of the literature provides evidence
      of only level 3 and 4. Since length, location, extent and calibre of the urethral
      stricture have an important impact on prognosis, diagnosis and the role of
      ultrasonography are discussed. Pathophysiology of wound healing is discussed in
      relation to urethrotomy, as it explains the outcomes of the procedure. Operative
      techniques using cold knife and laser, use of endoprostheses, indications,
      complications, results and postoperative management are described. The possible
      role of urethral catheters, hydraulic dilatations and corticosteroid applications
      are discussed.

PMID- 16970070
TI  - [Rupture of corpora cavernosa: clinical practice].
AB  - Rupture of corpora cavernosa is a rare disease in young adults. In western
      countries, the most frequent cause is the so-called "faux pas du coit". In the
      Middle East, masturbation and penis manipulations aimed at stopping morning
      erection are the most frequent causes. The fracture which is audible by the
      patient is accompanied by a rapid detumescence with progressive onset of a
      haematoma. Diagnosis is based on clinical findings but radiological
      investigations such as MRI, ultrasonography or cavernography may help localizing
      the exact fracture site. The treatment of albugineal ruptures is surgery, in an
      elective manner whenever possible; it consists in the eviction of the
      subcutaneous haematoma, the suture of the albuginea and treatment of a
      potentially associated urethral rupture. Conservative treatment is exceptional
      and limited to patients who reject surgery, since it generates more
      complications: painful erections, persistent haematoma with a risk of infection,
      arteriovenous fistula, impotence, and unrecognized urethral rupture. Patients
      must be clearly informed on all these complications.

PMID- 16970071
TI  - [Phage types and virulence markers of clinical isolates of Salmonella
      enteritidis].
AB  - A set of 487 clinical isolates of Salmonella Enteritidis were phage typed and
      analyzed for virulence markers, i.e. bacterial cell surface hydrophobicity,
      motility, biofilm formation and the presence of a 60 kb serovar-specific
      virulence plasmid. The most frequent phage type was PT8 (48.3%), followed by
      PT13a (7.2%), PT15 (6.4%), and PT4 (4.5%). Thirty-one (6.4%) strains were non
      typeable. As many as 128 (26.3%) strains showed hydrophobicity in the hydrocarbon
      xylene adherence assay, with the highest percentages of highly hydrophobic
      strains being found among the following phage types: PT9a (84.6%), PT25 (81.8%),
      PT15 (54.8%) and PT8 (23.4%). Motility > or = 50 mm was observed in 294 (60.4%)
      strains and visible biofilm was formed in the test tube assay in different
      degrees by 448 (91.9%) strains. The capacity of in vitro biofilm formation is
      indicative of a high virulence potential of the study strains. The 60 kb serovar
      specific virulence plasmid was present in 467 (95.9%) strains. Clear correlation
      between phage types and particular virulence markers was not revealed in the
      study set of strains. The obtained in vitro results are suggestive of flexibility
      of Salmonella Enteritidis in infecting the host.

PMID- 16970072
TI  - [Aeromonas spp. as the causative agent of acute diarrhoea in children under 1
      year of age].
AB  - STUDY OBJECTIVE: To establish whether there is a link between cases of acute
      watery diarrhoea and a specific Aeromonas species. MATERIALS AND METHODS: Eight
      strains studied were identified as aeromonads and were further characterized by
      biochemical tests, fatty acid analysis and ribotyping. RESULTS: Aeromonads were
      isolated repeatedly from stool specimens of four children under one year of age
      with acute diarrhoea, two of whom were admitted to hospital. Of eight isolated
      aeromonads strains six were identified as A. caviae, one was classified into A.
      veronii bv. sobria and one could not be identified to the species level. Only two
      A. caviae strains from one patient were found to be identical by ribotyping while
      the Aeromonas species (strains) isolated from the other cases differed from one
      another. Contaminated fresh water, contaminated food and contact with travellers
      with imported diarrhoea were identified as probable sources of infection.
      CONCLUSION: Four cases of acute gastroenteritis in small children document that
      aeromonads are not rare and can cause serious health problems. However,
      epidemiological links remain unclear. We did not prove correlation between the
      four serious cases of acute diarrhoea and specific Aeromonas species but the
      results suggest the predominant role of A. caviae.

PMID- 16970073
TI  - [Seroprevalence of antibodies against hepatitis A virus and hepatitis B virus in
      nonvaccinated adult population over 40 years of age].
AB  - STUDY OBJECTIVE: To determine prevalence rates of antibodies against hepatitis A
      virus (HAV) and hepatitis B virus (HBV) in the general adult male and female
      population over 40 years of age with no history of viral hepatitis A (VHA) and
      viral hepatitis B (VHB) who have never been vaccinated against hepatitis and to
      assess the cost-effectiveness of the pre-vaccination serological screening.
      MATERIAL AND METHODS: In 2003-2004, a total of 972 persons of three age
      categories: 41-50 years, 51-60 years, 61 and more years, were screened. Persons
      with a history of VHA and/or VHB and those who had been vaccinated against
      hepatitis were not included in the study. The following four indicators were
      determined from a 5 ml specimen of whole venous blood by electrochemiluminiscence
      assay: total anti-HAV antibodies, total anti-HBc antibodies, anti-HBs antibodies
      and HBsAg, as the most suitable markers of experienced hepatitis or previous
      vaccination. RESULTS: The prevalence rates of anti-HAV antibodies were lower in
      females compared to males for all of the three age categories. These antibodies
      were detected in 16.8%, 52.9% and 77.5% of 41-50-year-olds, 51-60-year-olds and >
      or = 61-year-olds, respectively. The total prevalence rate for the three age
      groups was 61.6%. The anti-HBc antibody seroprevalence rates were 1.9%, 5.3% and
      6.1%, respectively. CONCLUSION: The results show high prevalence of VHA in higher
      age groups. Such a high seroprevalence of antibodies in nonvaccinated persons
      with no history of viral hepatitis is suggestive of a very frequent incidence of
      asymptomatic infection. For this reason, the prevaccination screening of anti-HAV
      antibodies is cost-effective in the population over 50 years of age but is not
      justified in persons under 40 years of age. Prevaccination screening for anti-HBc
      antibodies appears not to be cost-effective regardless of age in view of their
      low prevalence in the Czech population.

PMID- 16970074
TI  - [Molecular detection and subtyping of Treponema pallidum subsp. pallidum in
      clinical specimens].
AB  - An in-house two-step nested PCR amplification targeting the tmpC gene (TP0319,
      encoding putative membrane lipoprotein) was used for detection of chromosomal DNA
      of Treponema pallidum subsp. pallidum in clinical specimens. We tested 138 blood
      serum samples from 111 adult patients with suspected, primary, secondary, early
      or late latent syphilis. T. p. pallidum DNA was not detected in any of the
      analyzed specimens. Out of 11 mucocutaneous swabs (7 genital and 4 pharyngeal), 6
      collected from 3 patients with primary or secondary syphilis tested positive. One
      skin swab from a patient with early congenital syphilis was also positive as were
      his serum and cerebrospinal fluid samples. DNA sequencing of the genes TP0136 and
      TP0548 from the positive samples revealed two strains with DNA sequences
      identical to that of T. p. pallidum strain SS14 and two unique previously
      undescribed T. p. pallidum strains. The advances in molecular typing of T. p.
      pallidum in clinical specimens will be of relevance to the epidemiology of
      syphilis and will allow for clinical discrimination between reinfection and
      syphilitic reactivation.

PMID- 16970075
TI  - [Pediatric head lice: taxonomy, incidence, resistance, delousing].
AB  - Based on the current knowledge, head louse (Pediculus capitis) and body louse
      (Pediculus humanus) are two different species that infest specific parts of the
      human body and do not interbreed in vivo. In 1991-2002, 6 257 cases of
      pediculosis were reported in the Czech Republic while 3 138 000 pediculicide
      packagings, i.e. about 500 times as many as the number of cases, were marketed.
      Between October 2004 and February 2005, a total of 531 children aged between 6
      and 15 years from 16 selected schools in the Zlin and Olomouc regions were
      screened by dry hair combing. Living lice were detected in 14.1% of the enrolled
      children and dead nits alone were observed in other 9.8% of the subjects. In
      vitro tests revealed that the collected head lice were highly resistant to
      malathion, the active ingredient of Diffusil H 92 M. The number of reported cases
      of pediculosis roughly doubled in 2005.

PMID- 16970076
TI  - [A comparative analysis of types, causes and circumstances of deaths based on
      autopsy reports from the periods of 1945-50 and 1990-1993].
AB  - The authors presented a comparative analysis of types of deaths, their causes and
      circumstances based on autopsy reports of postmortem examinations performed in
      the Department of Forensic Medicine in Lodz in the years 1945-1950 (1210
      reports), and in the period 1990-1993 (1393 reports). In both the analyzed time
      frames, the most common type of death was violent deaths (59,88% and 78,39%,
      respectively). Gunshot wounds were a far more common cause of death in 1945-50 as
      compared to 1990-93 (16,99% and 0,92% of all violent deaths, respectively). In
      the years 1990-1993, the incidence rate of blunt injures was much higher than in
      the previous period (38,12% and 51,37% of all violent deaths, respectively),
      similarly as ethanol poisonings (4,42% and 10,44% of all violent deaths,
      respectively). In almost one half of instances, the available archival records
      for the years 1945-50 did not allow for determining the circumstances of deaths
      (42,82% of all violent deaths); in the years 1990-1993, the majority of deaths
      occurred in consequence of accidents (60,26% of all violent deaths). Contrary to
      expectations, the ratio between road traffic-related and other accidents
      increased only slightly in the years 1990-1993 as compared to the period of 1945
      1950 (traffic accidents: 61,09% and other accidents: 38,91% of all accidents in
      the first period, vs. traffic accidents: 57,62% and other accidents: 42,38% of
      all accidents in the second period).

PMID- 16970077
TI  - [Fatal traffic accidents vs. alcohol consumption in the victims in the archival
      material collected by the Institute of Forensic Medicine, Collegium Medicum,
      Jagiellonian University in Cracow, in the years 2000- 2003].
AB  - The report presents the issue of fatal traffic accidents, emphasizing in
      particular blood alcohol levels in victims involved in such fatalities. According
      to data provided by the Central Police Headquarters, in recent years, the annual
      number of traffic accidents in Poland has been in excess of 50000; of this
      number, more than 10% have resulted in fatalities. The number of traffic
      accidents in the Malopolska province has amounted to 5000, and more than 7% of
      these accidents have been fatal. In the years 2000-2003, at the Department of
      Forensic Medicine, Collegium Medicum, Jagiellonian University, a total of 884
      victims of fatal traffic accidents that occurred in the Cracow region were
      autopsied. In the group, car drivers accounted for 26%, passengers - for 16%,
      while the most numerous subgroup, represented by more than 57% of victims,
      included pedestrians hit by moving vehicles. In the autopsied car drivers,
      individuals being under the influence of alcohol and intoxicated accounted for 40
      42% in the years 2000-2002 (as compared to the total number of investigated
      subjects); in 2003, the percentage decreased reaching 31%. Among the passengers,
      the mean percentage of those being under the influence of alcohol and in drunk
      was slightly higher in this period, ranging between 27 and 57%. However, the
      highest percentage of victims included individuals under the influence of
      alcohol, and especially alcohol intoxicated pedestrians hit by moving vehicles,
      whose number exceeded 50% of the total group of the autopsied corpses.

PMID- 16970078
TI  - [Mental or physical disorders of people who committed suicide in penitentiary
      institutions in Poland in the years 1995-1997].
AB  - The study proves that mental disorders (mainly depression) rank among the main
      motives of suicidal behaviors, which are triggered by, for example,
      disadvantageous social factors. In the material under study, 27,7% of the inmates
      were treated at a mental ward and as many as 31,07% constituted the patients of
      Outpatient Mental Health Clinic. Hence, the high percentage--a total of 58,4% of
      mentally disturbed individuals--constituted the group at an increased risk of
      autoaggressive reactions. The percentage of individuals outside the psychiatric
      treatment amounted to 41,6%, this being the people who, in spite of deviations
      from the mental norm, failed to visit or did not deem it necessary to consult the
      mental health clinic. In the ICD-10 classification of mental disorders, the most
      numerous group among the inmates who committed 3a fatal suicidal attempt included
      individuals with behavior and personality disorders (F60-F69). These constituted
      55.9% of the total number of suicides. The less numerous group (26.7%) consisted
      of the inmates with mental disorders and behavior deviations caused by
      psychoactive substances (F10-F19). The third group of suicides (13.9%) included
      individuals with organic mental disorders, including symptomatic syndromes (F00
      F09). These three groups accounted for 96.1% of the total number of suicides.

PMID- 16970079
TI  - [Cardiovascular diseases in medico-legal opinions on work disability].
AB  - The paper presents the results of a study of cases judged by the District Court
      in Piotrkow Trybunalski in 2004, in which petitioners sought permanent work
      disability benefits on grounds of cardiovascular diseases. The largest group of
      petitioners included those with hypertension, coronary disease and a history of
      myocardial infarction. The largest percentage of persons judged to be work
      disabled were those having suffered a myocardial infarction, but this was true
      also for individuals with cardiomyopathies, as well as cardiac rhythm and
      conduction disturbances. Disorders judged to pose the least limitation on the
      ability to work encompassed non-specific pain in the thoracic cavity, and
      hypertension.

PMID- 16970081
TI  - [Polymorphism of the locus HUMHUU in the Polish population--a preliminary
      report].
AB  - The paper presents the results of a population study on the locus HUMHUU, which
      is a non-coding fragment of human DNA built of four nucleotide repeats (CTTT)n,
      localized on the 16th chromosome. The studies, carried out on a group of 200 non
      related individuals, showed the presence of 14 different alleles, from 150 to 200
      bp in length. Biostatistical calculations demonstrated that the expected
      heterozygosity was 0,830301 +/- 0,018768, PD - 0,949156, PIC - 0,806888, PE -
      0,662444, PE for motherless cases - 0,491305, and the average paternity index -
      2,946389. The results obtained during the studies of the locus HUMHUU allow for
      recognizing it as a marker of personal identification useful for the needs of
      both criminalistics and disputed paternity testing.

PMID- 16970080
TI  - [STR polymorphism of the non-coding human growth hormone gene (HUMGHCSA) and its
      use in personal identification--a preliminary report].
AB  - The HUMGHCSA locus, located within the non-coding region of the human growth
      hormone gene on chromosome 17, exhibiting polymorphism of the number of repeats
      of two and four nucleotide motifs (CT and CTTT), but also polymorphism caused by
      nucleotide substitution, is one of the most polymorphic STR markers. The purpose
      of this study was to report the development of a system of fluorescent analysis
      for an automatic sequencer, to test its reliability and to develop biostatistical
      parameters of its usefulness in forensic examinations. The studies, carried out
      on a group of 200 non-related individuals, showed the presence of 24 different
      alleles, of 221 to 279 bp in length. Biostatistical calculations demonstrated
      that the expected heterozygosity was 0,898634 +/- 0,015091, PD - 0,980586, PIC -
      0,887709, PE - 0,792767, PE for motherless cases - 0,6556701, and the average
      paternity index - 4,932625. Such results indicate a High usefulness of the
      studied HUMGHCSA locus for identification examinations.

PMID- 16970082
TI  - [Determining post mortem interval by temperature data. Part II: research results
      from the 1970s to the end of the 20th century].
AB  - The study reviews the literature on the determination of the post mortem interval
      by temperature data. Because of the vast volume of material, the review is
      presented in two parts. In the present--second-part, the state of contemporary
      knowledge is described, beginning with papers originating from the 1970s and
      ending with later reports published up to the end of the 20th century.

PMID- 16970083
TI  - [Myocardial ischemia of the driver as a cause of a traffic road accident.
      Immunohistochemical C9 staining method in diagnostics of early myocardial
      infarction].
AB  - The authors presented a case of verification of pathological lesions as a cause
      of traffic accident where the driver--the culprit--was a fatal victim due to
      multiple injuries. Histopathological examination of postmortem samples of
      myocardium was conducted, using the hematoxylin-eosin, Nielsen-Selye and
      immunohistochemical C9 staining methods in order to verify the hypothesis about a
      possible myocardial ischemia triggering the accident. The results of "routine"
      (H&E) and--especially--immunohistochemical C9 staining showed myocardial damage
      due to ischemia, which was a morphological indicator evidencing the cause of
      "misbehavior" of the driver.

PMID- 16970084
TI  - [Allelic variant 6' at locus D13S317 in a paternity casework; a semi-automatic
      genotyping problem].
AB  - During a routine paternity casework, performed with automated genotyping using an
      AmpFISTR Identifiler kit, an inconsistency affecting maternal segregation of
      D13S317 allele was encountered, manually detected as a variant allele in the
      mother and child. Alleles of the putative father were transmitted in 13 out of 15
      autosomal STR loci, but in CSF1PO locus, there was an apparent mutation. We,
      therefore, directly sequenced the variant D13S317 allele in the mother and the
      child and compared the results to the available data on variant alleles within
      this STR locus. The variant allele consisted of 6 TATC repeats and an additional
      AATC motif, thus, by a similarity to the previously reported variant, it was
      labeled D13S317.6'. It seems that the variant allele is quite rare in the Polish
      population, however, its electrophoretic mobility between preceding TH01 alleles
      and that of D13S317 one, requires a careful scrutiny of automated genotyping
      traces to avoid misinterpretation of the results.

PMID- 16970085
TI  - [Death of a 57-year old male with previously undiagnosed displacement of the
      abdominal organs to the chest].
AB  - The report describes a death of a 57-year old male who died due to exacerbated
      cardiac and pulmonary insufficiency caused by the displacement of the abdominal
      organs to the chest through a previously undiagnosed diaphragmatic hernia.

PMID- 16970086
TI  - [Cohort study on fuzheng capsule and quxie capsule in reducing relapse and
      metastasis of cancer in patients with stage II and III colorectal carcinoma after
      operation].
AB  - OBJECTIVE: To study the effect of Fuzheng Capsule (FC) and Quxie Capsule (QC) in
      reducing relapse and metastasis of colorectal cancer in stage II and III after
      the cancer had been treated by radical operation and succedent routine
      radiotherapy and chemotherapy. METHODS: A prospective cohort controlled study was
      conducted in 101 patients with colorectal cancer in stage II and III after
      radical operation and routine radiotherapy and chemotherapy, among whom 53
      patients were treated with FC and QC and 48 were given no treatment, they were
      followed up regularly. The rate and time of relapse and metastasis were observed
      after 1, 2 and 3 years. RESULTS: One-year, 2-year and 3-year relapse-metastasis
      rate was 0, 2.7% and 14.8% respectively in the treated group, and 6.2% , 24.2%
      and 30.8% in the control group. Significant difference was found only in the 2
      year rate between the two groups (chi-squared = 5.428, P < 0.05). Average time of
      relapse and metastasis was 26.2 +/- 4.5 months in the treated group and 14.2 +/-
      4.2 months in the control group, showing significant difference between the two
      groups (P < 0.05). CONCLUSION: FC and QC applying in the succedent consolidating
      treatment for stage II and III colorectal cancer after radical operation might be
      favourable to reduce relapse and metastasis and improve quality of life, further
      clinical study with randomized and controlled method is worthwhile to be
      conducted.

PMID- 16970087
TI  - [Clinical observation on treatment of 75 mid-late stage cancer patients with
      yanshu Injection].
AB  - OBJECTIVE: To study the effect of Yanshu Injection (YI) used in comprehensive
      treatment on mid-late stage cancer. METHODS: One hundred and fifty patients with
      malignant cancer were equally randomized into the comprehensive treatment group
      (group A) and the control group (group B), both groups were treated
      systematically according to the NCCN 2005 cancer practice guideline, but 20 ml of
      YI was given additionally to group A every day. RESULTS: After treatment, the
      level of plasma CD4 and CD4/CD8 ratio were significantly lower in group B than
      those in group A (P < 0.05); the response rate (RR) was 32.00% (24/75) and 38.67%
      (29/75) in group B and A respectively, showing insignificant difference (P>0.05),
      and the clinical benefit rate (CBR)was 58.67% (44/75) in group A, lower than that
      in group B (85.33% (64/75), P< 0.05); the quality of life (QOL) in group A was
      superior to that in group B (P<0.05); and the incidence of main adverse reaction
      to chemotherapeutic agents was significantly lower in group A as compared to that
      in group B (P<0.05). CONCLUSION: YI could regulate the function of T-lymphocyte
      subsets, raise the CBR and QOL and reduce adverse reaction of chemotherapy in
      patients with mid-late stage cancer.

PMID- 16970088
TI  - [Effect of erzhi tiangui recipe on ovarian reactivity in elderly sterile women].
AB  - OBJECTIVE: To observe the clinical effect of Erzhi Tiangui Recipe (ETR), a
      traditional Chinese recipe for strengthening Shen and nourishing Tiangui, in
      improving the ovarian reactivity in elderly sterile women. METHODS: Sixty-six
      elderly sterile women receiving in vitro fertilization pre-embryo transfer (IVF
      ET) were randomly divided into two groups: the ETR group treated with ETR plus
      follicle stimulating hormone (FSH) and the control group treated with FSH alone,
      33 cases in each group. Changes of symptoms and the relative parameters were
      observed, including the dosage of FSH used, the serum hormone levels at different
      periods, endometrium thickness and arteriopalmus of uterus and ovary on the day
      of HCG injection, follicle number, follicular oocyte number, mature follicular
      oocyte rate and fertilization rate, prime embryo rate, and pregnancy rate.
      Moreover, the correlation of the symptom score of colpoxerosis (CR2) and serum
      estradiol (E2) level was analyzed after treatment (on the HCG injection day).
      RESULTS: Symptoms of Shen qi-yin deficiency were improved significantly in the
      ETR group, with the improvement better than that in the control group (P < 0.05).
      The total and daily FSH dosage in the ETR group were lower than those in the
      control group, showing significant difference between the two groups (P < 0.05).
      The effects were better in the ETR group than those in the control group in
      increasing serum E2 and endometrium thickness on the HCG injection day, and also
      in elevating the follicular oocyte number, the mature oocytes rate, the
      fertilization rate, and the prime embryo rate (all P < 0.05). CR2 analysis showed
      low negative correlation in both groups (r = -0.369 in the ETR group and r = 
      0.425 in the control group), suggesting E2 could be one of the factors but not
      the only factor for influencing colpoxerosis. And the score of colpoxerosis was
      lower in the ETR group after treatment than that in the control group (t = 2.422,
      P < 0.05). CONCLUSION: ETR combined with FSH can obviously reduce the dosage of
      FSH used, improve ovarian reactivity and pregnancy rate, and improve the quality
      of oocytes, the mechanism is possibly related with its effects in improving
      ovarian reactivity elevating blood estrodiol and regulating the hypothalamus
      pituitary-ovary axis (HPOA).

PMID- 16970089
TI  - [Study on the differential gene expression of peripheral CD4+ among rheumatoid
      arthritis patients of cold or heat syndrome type with or without rheumatoid
      factor].
AB  - OBJECTIVE: To explore the differential gene expression of peripheral CD4+ among
      rheumatoid arthritis (RA) patients of cold or heat syndrome type with or without
      rheumatoid factor (RF). METHODS: Differential gene expression of peripheral CD4+
      lymphocytes purified from fasting venous blood of RA patients and healthy
      subjects was studied using gene chip technique. RESULTS: There were 55
      differential genes between RA patients with and without RF, mainly involving
      those related with immune response and signal transduction. In patients with RF,
      71 differential genes, mainly related with functional metabolism and immune
      response, and in those without RF, 70 related with functional metabolism were
      found between patients of cold and heat syndrome type respectively, all of them
      were not repetitive with the above-mentioned 55, and only 2 were found repetitive
      between the 70 and the 71 differential genes, mainly involving functional
      metabolism. CONCLUSION: The differential genes between RA patients with or
      without RF are different with those between patients of heat and cold syndrome
      type, suggesting the TCM syndrome classification has its own basis of gene
      expression profile.

PMID- 16970090
TI  - [Study on the patterns of TCM syndrome differentiation of 900 patients with
      posthepatitic cirrhosis].
AB  - OBJECTIVE: To investigate the formula for TCM syndrome pattern differentiation in
      patients with posthepatitic cirrhosis. METHODS: Factors analysis, C mean
      clustering and fuzzy comprehensive assessment were used for analyzing the basic
      information, including clinical symptoms and signs, obtained from 900 patients
      with posthepatitic cirrhosis to establish the formula for syndrome pattern
      differentiation through collecting the syndromic factors. RESULTS: Multivariate
      statistic analysis showed the syndromic factors could be classified into two
      categories: the common characteristics related factors, which reflected the basic
      pathology of cirrhosis as qi deficiency and blood stasis, and the factors for
      differentiating 5 syndrome patterns (Gan-Shen yin-deficiency, dampness-heat
      accumulation, stasis-heat accumulation, Gan-qi stagnation with Pi-deficiency, and
      Pi-Shen qi-deficiency), which reflected the different pathological features of
      different syndrome patterns, showing the complexity and polymorphism of syndrome
      construction. And the functional formula for differentiating syndrome pattern was
      established. CONCLUSION: The differentiating formula of TCM syndrome pattern
      could provide a quantified criterion for syndrome pattern differentiation in
      posthepatitic cirrhosis patients.

PMID- 16970091
TI  - [Relationship between the polymorphism of alpha-adducin gene and the two
      phenotypes of constitutions in patients with essential hypertension classified by
      TCM].
AB  - OBJECTIVE: To investigate the relationship between the polymorphism of alpha
      adducin (ADD1) gene and the two phenotypes of constitution in patients with
      essential hypertension, the Yang-hyperactive (YH) type and phlegm-dampness (PD)
      type, classified by traditional Chinese medicine (TCM) approach. METHODS: Two
      hundred and seven patients differentiated by TCM approach as YH type (113 cases)
      or PD type (94 cases) were observed, with the systolic blood pressure (SBP),
      diastolic blood pressure (DBP), body mass index (BMI), fasting blood glucose
      (FBG), serum creatinine (Cr), uric acid (UA), total cholesterol (TC) and
      triglycerides (TG) as the criteria of observation. Gly460Trp polymorphism of the
      ADD1 gene was detected by MALDI-TOF mass spectrometry. Results The levels of BMI,
      DBP, FBG and UA, etc. in the PD group were significantly higher than those in the
      YH group respectively. The rate of GG, GT and TT type of ADD1 gene was 29.2%,
      41.6% and 29.2% in the YH group, 28.7%, 48.9% and 22.3% in the PD group, showing
      no significant difference in ADD1 genotype distribution between the two groups,
      while there was also no difference in the hypertension phenotype distribution
      among different genotypes (both P > 0.05). For the patients with TT genotype,
      there were significant differences between the YH group and the PD group in BMI
      (24.11 +/- 3.04 kg/m2 vs 26.20 +/- 2.30 kg/m2), DBP (96.79 +/- 4.05 mmHg vs 99.56
      +/- 3.90 mmHg), FBG (5.01 +/- 0.53 mmol/L vs 5.51 +/- 1.07 mmol/L) and UA level
      (302.22 +/- 71.95 micromol/L vs 358.25 +/- 88.75 micromol/L, all P < 0.05).
      CONCLUSION: There was no relation between ADD1 gene polymorphism and the TCM
      genotype of constitution in patients with essential hypertension. However, it is
      likely that for hypertension patients with TT genotype, those of PD type are more
      susceptible to cardiovascular disease and have worse prognosis than those of YH
      type.

PMID- 16970092
TI  - [Relationship between quality of life and TCM syndrome types in patients with
      diabetes mellitus].
AB  - OBJECTIVE: To explore the relationship between the syndrome types differentiated
      by traditional Chinese medicine and the quality of life (QOL) in patients with
      diabetes mellitus (DM). METHODS: The QOL in patients was investigated with Short
      Form-36 questionnaire (SF-36), and compared with that of healthy subjects for
      control; the TCM syndrome type was differentiated at the same time by the
      outcomes of symptoms acquired from the questionnaire. RESULTS: The score of all
      the domains of QOL was respectively lower in the DM patients than that in the
      healthy subjects. The score of some domains of QOL showed correlation with
      different TCM syndrome types. CONCLUSION: QOL of DM patients significantly
      decreased. The variation of syndrome types could significantly influence some
      domains of QOL.

PMID- 16970093
TI  - [Effect of yuquan pill on proinflammatory cytokines in patients with type 2
      diabetes mellitus].
AB  - OBJECTIVE: To observe the effect of Yuquan Pill (YP) on proinflammatory cytokines
      in patients with type 2 diabetes mellitus (DM2). METHODS: Ninety patients with
      DM2 were randomly divided into the treated group and the control group by the
      ratio of 2:1. Both groups were treated with Glucobay on the base of dietary and
      exercise therapy for 3 months, with YP, given to the treated group additionally 6
      g four times a day. And the changes of proinflammatory cytokines, including C
      reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6
      (IL-6), etc. were observed. RESULTS: The levels of serum CRP,TNF-alpha and IL-6
      significantly lowered after treatment in both groups (P<0.01), and the
      improvement in the treated group was superior to that in the control group
      (P<0.01). CONCLUSION: YP could reduce the levels of the increased proinflammatory
      cytokines in patients with DM2.

PMID- 16970094
TI  - [Experimental study on effects of electro-acupuncture in improving synaptic
      plasticity in focal cerebral ischemia rats].
AB  - OBJECTIVE: To explore the mechanisms of electro-acupuncture (EA) in improving
      synaptic plasticity after cerebral ischemic injury. METHODS: Focal cerebral
      ischemia (FCI) model was established by middle cerebral artery occlusion (MCAO)
      with heat-coagulation method. The changing rules of synaptic ultrastructure,
      synaptophysin (P38), growth-associated protein-43 (GAP-43), brain-derived
      neurotrophic factor (BDNF) and nerve growth factor (NGF) in the ischemic cortex 2
      and 5 weeks after FCI and the effects of EA on them were observed. RESULTS:
      Expression of numerical density (Nv), surface density (Sv), volume density (Vv),
      post synaptic density (PSD) and P38 in the ischemic cortex significantly
      decreased after MCAO (P<0.01). Among them, Nv and Sv were raised at the 5th week
      in FCI rats either treated or untreated with EA (P<0.01), but the increment of Sv
      was higher in those of the treated rats (P<0.01); PSD in the EA treated rats also
      showed a significant increase at the 5th week, which was significant higher than
      that in those untreated; EA showed insignificant influence on Vv and synaptic
      interfacial curvature; P38 lowered continuously after 2 weeks, but at the 5th
      week, it was higher in EA treated rats than that in untreated rats (P<0.01),
      while at the 2nd week, the levels in treated and untreated rats were equal. GAP
      43 rose in the 2nd week after modeling, with no difference between EA treated and
      untreated animals, at the 5th week, it was lowered in untreated rats to near that
      in sham-operated rats, but maintained at higher level in EA treated rats; NGF and
      BDNF positive cells significantly increased after modeling (P<0.01), and showed a
      descending trend with the time going (P<0.01) both in rats treated or untreated
      with EA. CONCLUSION: EA can protect synaptic ultrastructure, promote the
      expression of P38, GAP-43, NGF and BDNF in the ischemic cerebral cortex, and thus
      improve synaptic plasticity in cerebral ischemic rats.

PMID- 16970095
TI  - [Protective effects of triptolide on the lipopolysaccharide-mediated degeneration
      of dopaminergic neurons in substantia nigra].
AB  - OBJECTIVE: To study the protective effects of triptolide (Tri) on the
      lipopolysaccharide (LPS)-mediated degeneration of dopaminergic neurons in
      substantia nigra. METHODS: Forty SD rats were randomly divided into four groups:
      the sham group, the LPS model group, the Tri group and the normal saline group,
      10 in each group. Fourteen days later, the apomorphine-induced rotational
      behavior, the content of dopamine (DA) and its metabolites in the striatum of the
      injured side, the number of tyrosine-hydroxylase (TH) positive neurons and
      activation of microglia in rats were observed. RESULTS: Injection of LPS in
      substantia nigra could induce cerebral simulated immunoinflammatory reaction,
      leading to degeneration of dopaminergic neuron and induce ipsilateral directed
      rotational behavior of rats, which could be improved by Tri. Moreover, Tri could
      raise the lowered content of DA and its metabolites as well as the TH positive
      neurons in striatum, and suppress the activation of microglia significantly
      (P<0.01). CONCLUSION: Tri could protect the dopaminergic neurons from
      degeneration due to the inflammation mediated by LPS through inhibiting the
      activation of microglia.

PMID- 16970096
TI  - [Effect of three-stage sequential method on interleukin-5 mRNA expression in the
      lung tissue of asthmatic model rat treated with steroid].
AB  - OBJECTIVE: To observe the effect of three-stage sequential method (TSSM) on
      interleukin-5 (IL-5) mRNA expression in the lung tissue of asthmatic rat model
      treated with steroid. METHODS: SD rats were randomly divided into 8 groups, the
      normal control group (GA), the model group (GB), the model with steroid
      intervention group (GC) and the 5 treated groups (GD - GH). Excepting those in
      the GA, all rats were established into the asthma model and rats in GC-GH were
      intervened by dexamethasone, with the dosage reduced by 0.1 mg/kg per week
      starting from the 3rd week and withdrawn completely till the 7th week. At the
      same time, rats in GD - GH were treated with TSSM, and the 1st, 2nd and 3rd
      recipe of TSSM, as well as pulmicort respules (as positive control) respectively.
      IL-5 mRNA expression in the lung tissue of rats was detected at different time
      points by in situ hybridization. RESULTS: Comparisons of GD with other groups in
      IL-5 mRNA expression showed: it was remarkably lowered than that in GB and GC at
      all time points (P < 0.01); compared to GH, the difference was insignificant at
      the end of the 2nd week, but significant at the end of the 7th and 9th week (P <
      0.01); as for the difference between GD with GE, GF and GG, it showed very
      significant difference (P < 0.01) at all the time points besides that at the end
      of the 2nd week, it showed insignificance to GE (P > 0.05) and significance to GF
      (P < 0.05). The dynamic changes of IL-5 mRNA expression in GD during the steroid
      withdrawal period showed the lowering was more significantly at the end of the
      7th and 9th week than that at the end of the 2nd week (P < 0.05, P < 0.01), but
      its levels were equal at the former two time points; its lowest level appeared at
      the end of the 9th week, which approaching the level in GA (P > 0.05).
      CONCLUSION: Three-stage sequential method could remarkably inhibit IL-5 mRNA
      expression in the lung tissue of asthmatic rats undergoing steroid treatment.

PMID- 16970097
TI  - [Effects on herba epimedii and radix Astragali on tumor necrosis factor-alpha and
      nuclear factor-kappa B in asthmatic rats].
AB  - OBJECTIVE: To observe the effects of Herba Epimedii and Radix Astragali, the two
      Chinese herbs for replenishing Shen and strengthening qi, on tumor necrosis
      factor-alpha (TNF-alpha, one of the pro-inflammatory factors) and nuclear factor
      kappa B (NF-kappa B) in asthmatic rats. METHODS: Rats were randomly divided into
      five groups: the normal saline control group, the asthma model group and the
      three treated groups treated with high, medium and low dose of the Chinese herbs.
      Serum TNF-alpha and NF-kappa B activity in pulmonary tissue were detected with
      enzyme-linked immunosorbent assay and immunohistochemistry respectively. RESULTS:
      Herba Epimedii and Radix Astragali could effectively reduce the production of TNF
      alpha and inhibit NF-kappa B activity, and the efficacies in the three treated
      group were similar, showing insignificant difference among them. CONCLUSION:
      Application of Herba Epimedii and Radix Astragali in the attack or remission
      stage of asthma could restrain the development of inflammation by reducing the
      production of TNF-alpha and inhibiting NF-kappa B activity.

PMID- 16970098
TI  - [Effects of shuangshen ningxin capsule on mini-porcine myocardial ischemia model
      induced by thrombosis via cardiac catheterization intervention].
AB  - OBJECTIVE: To investigate the establishment of mini-porcine myocardial ischemia
      (MI) model induced by thrombosis via cardiac catheterization intervention, and
      observe the anti-MI action of Shuangshen Ningxin Capsule (SNC). METHODS: MI model
      of Chinese mini-porcine was established by injection of self-thrombus in left
      anterior descending coronary artery (LAD) with guiding catheter through carotid
      artery. The effect of SNC on MI was evaluated comprehensively by analyzing the
      parameters as coronary embolism, 30 dots surface mapping electrocardiogram and
      quantitative histology, etc. RESULTS: LAD in the model animals was basically
      embolized 6 days after modeling, showing increase of amplitude and dot of ST
      segment elevation. After being administered with SNC for 6 days, the self
      thrombus blocked LAD was recanalized and the degree and extent of MI reduced.
      CONCLUSION: It is the first time to successfully establish MI model of Chinese
      mini-procine by thrombosis via cardiac catheterization intervention. SNC has anti
      MI effect.

PMID- 16970099
TI  - [Clinical observation on shufei granule in improving right ventricular function
      of patients with chronic pulmonary heart disease].
AB  - OBJECTIVE: To observe the effect of Shufei Granule (SG) on right ventricular
      function in patients with chronic pulmonary heart disease (CPHD). METHODS: One
      hundred CPHD patients were randomly divided into two groups, the control group (n
      = 40) treated with fleroxacin 0.2 g twice per day by intravenous dripping and
      diprophylline 0.2 g 3 times per day orally, the treatment group (n = 60) treated
      with SG 10 g 3 times a day orally additionally besides the treatment given to the
      control group. The therapeutic course for both groups was 3 weeks. The changes of
      the cardiac function, the right ventricular function [A peak velocity (VA), E
      peak velocity (VE), VA/VE, systolic pulmonary artery pressure (SPAP), pre
      ejection period (PEP), right ventricular ejection time (RVET), PEP/RVET], and
      blood-gas analysis were investigated, the condition of clinical symptoms and
      signs as well as tongue pictures were observed also. RESULTS: The total effective
      rate was 91.6% in the treated group, significantly higher than that in the
      control group (70.0%, P < 0.01); the improvements in symptom score, cardiac
      function and the other laboratory indexes were all superior in the treatment
      group to those in the control group (P < 0.05, P < 0.01). CONCLUSION: SG is an
      effective drug for improving right ventricular function in CPHD patients.

PMID- 16970100
TI  - [Effect of combined therapy of modified kangjia recipe combined with western
      medicine on hyperthyroidism].
AB  - OBJECTIVE: To observe the therapeutic effect of combined therapy of modified
      Kangjia Recipe (KR) and western medicine propylthiouracil (PTU) on
      hyperthyroidism and to assess its advantage. METHODS: Ninety patients with
      hyperthyroidism were divided into the treatment group (TG) and the control group
      (CG). The 60 patients in TG treated with KR and PTU, and the 30 patients in CG
      treated with PTU alone. The treatment course of both groups was 3 months. The
      serum thyroid hormone (TH) level, clinical symptoms and signs, and adverse
      reaction were observed before and after treatment. RESULTS: The serum TH level,
      clinical symptoms and signs were significantly improved after treatment in both
      groups (all P < 0.01). The total effective rate was 93.3% in TG, which was higher
      than that in CG (83.3%, P < 0.01); and the efficacy in improving palpitation,
      fidget, aversion to heat, sweating and insomnia was better in the TG than that in
      the CG respectively (P < 0.05). As for the incidence of adverse reaction, it that
      was lower in the TG than in the CG. CONCLUSION: KD has good efficacy in treating
      hyperthyroidism, and the combined treatment of Chinese and Western medicine shows
      obvious advantages.

PMID- 16970101
TI  - [Effects of electro-acupuncture on electroencephalography in patients with
      vascular dementia].
AB  - OBJECTIVE: To study the effects of electro-acupuncture (EA) on
      electroencephalography (EEG) in vascular dementia (VD) patients. METHODS:
      According to the Hasegawa dementia scale (HDS), the severity of 46 VD patients
      were classified into three grades as gentle, medium and severe, in the same time,
      they were divided into the EA group (n = 23) and the nimotop group (n = 23)
      randomly. Changes of EEG in the patients were observed before and after
      treatment. RESULTS: The degree of normality of EEG in VD patients were positively
      correlated with the severity of their illness, i. e. the severer VD, the more
      obvious the abnormal EEG changes. CONCLUSION: EEG can be accessible for
      evaluating the severity of VD, and the electrical activity of brain in VD
      patients could be improved by EA therapy.

PMID- 16970102
TI  - [Effect of TCM formula for promoting blood circulation to remove blood stasis on
      brainstem auditory evoked potential and Transcranial Doppler parameters in
      patients with sudden deafness].
AB  - OBJECTIVE: To observe the therapeutic effect of Xuefu Zhuyu Decoction (XZD) on
      patients with sudden deafness (SD). METHODS: Sixty patients with SD were treated
      with XZD, and the changes of brainstem auditory evoked potential (BAEP) and
      transcranial Doppler (TCD) parameters in them were detected before and after
      treatment and analyzed statistically. RESULTS: I, III and V waveform and peak
      latency (PL) of BAEP, velocity of vertebral basilar arterial blood flow and
      parameters of cerebral blood flow in SD patients were all improved to different
      levels after treatment with XZD. CONCLUSION: TCM formula for promoting blood
      circulation to remove blood stasis can improve BAEP and TCD parameters in SD
      patients; BAEP detection and TCD parameters can reflect nerve function and blood
      supply state of internal ear and brain stem, and therefore are of great
      importance in guiding the clinical treatment and assessing the prognosis.

PMID- 16970103
TI  - [Initial exploration on the new thought for diagnosis and treatment of systemic
      lupus erythematosus by integrative Chinese and Western medicine].
AB  - The pathological changes of systemic lupus erythematosus (SLE) could involve
      multiple organs and systems, showing a complicated and multivariate clinical
      features. Since the authors held that the previous clinical disease-syndrome
      integrative thought can not embody the regularity in the diagnosis and treatment
      of SLE, in order to establish a novel operable thought of syndrome
      differentiation which could reflect the clinical practice of SLE, they suggested,
      in accordance with their clinical experience, that the basis for integration of
      the disease and its syndromes should not be SLE itself but the clinical
      manifestations of the organs and systems, such as fever, nervous system injury,
      lupus kidney, thrombocytopenic purpura of SLE, etc. They claimed that the new
      clinical thought of diagnosis and treatment will contribute to conduct systematic
      and standard research on SLE, and the regulation of TCM therapy based on syndrome
      differentiation would be more closer to the clinical practice of SLE.

PMID- 16970104
TI  - [Answer to Xie and colleagues concerning the use of western medical terms to
      represent traditional Chinese medical concepts].
AB  - This paper rejects the Professor Xie's argument that the use of biomedical terms
      to represent traditional Chinese medical concepts is helpful to the
      internationalization of Chinese medicine [(Chin J Integr Tradit West Med 2005;
      25(11):1046-1049]. It further argues that this practice destroys the integrity
      and independence of Chinese medical concepts, taking the term feng huo yan as an
      example. This paper supports the viewpoint with numerous other examples that for
      those seeking a deep understanding of TCM, the literal translation (loan
      translation) is much more helpful.

PMID- 16970105
TI  - [Mnemonic strategy for english vocabulary of TCM fundamental theory formed by
      borrowing translation and morphemic translation from Western medical terms].
AB  - In the article, the importance and feasibility of borrowing translation and
      morphemic translation from Western medical terms for translating terms of TCM
      fundamental theory are briefly reviewed, and mnemonic strategy for the
      memorization of TCM vocabulary formed by the two translation methods is
      discussed.

PMID- 16970106
TI  - [Progress on research and application of traditional Chinese medicine in
      intervention treatment of primary liver carcinoma].
AB  - Status of research and application of traditional Chinese medicine (TCM) in
      intervention treatment of primary liver carcinoma in the latest three years was
      reviewed in this paper. The effects of TCM combining interventional therapy
      mainly embodied in three aspects: the anti-tumor action, the effects for
      treatment of embolism syndrome and the effects for preventing and treating
      recurrence and metastasis. And the keystone in further researches was also
      pointed out, it should be focused on anti-angiogenesis of tumor by TCM for better
      preventive and therapeutic effects on post-intervention recurrence and
      metastasis.

PMID- 16970107
TI  - [Progress of research on Chinese material medica serum and hepatic stellate
      cells].
AB  - The activation and proliferation of hepatic stellate cells (HSCs) is the central
      link in the formation and progression of liver fibrosis. From the research of
      serum pharmacological method of Chinese material medica, we found Chinese
      material medica serum could interfere in the formation and progression of liver
      fibrosis. This paper reviewed the progress on Chinese material medica serum and
      HSCs. The authors pointed out Chinese material medica serum could effect on the
      activation, proliferation, contraction and apoptosis of HSCs, which probably is
      an effective therapy for liver fibrosis.

PMID- 16970108
TI  - [The friend].

PMID- 16970109
TI  - [Th1 and Th2 lymphocytes in perennial allergic rhinitis].
AB  - BACKGROUND: The study of perennial allergic rhinitis is a good model to evidence
      the unbalance between Th1 and Th2 lymphocytes. This functional unbalance is
      manifested by the exaggerated production of pro-inflammatory cytokines and a
      reduction of the antiinflammatory ones. OBJECTIVE: To corroborate these
      alterations in patients with perennial allergic rhinitis. PATIENTS AMD METHOD: In
      nine patients with perennial allergic rhinitis who had no immunotherapy treatment
      we measured the IFNgamma, IL-4, IL-10 and IL-13 levels through a flow citometry.
      RESULTS: We found high levels of IL-10 (42%) and reduced IFNgamma values. We did
      not find IL-4 or IL-13 expressions in the studied patients. CONCLUSIONS: These
      results make us to consider a Th1/Th2 unbalance towards a Th2 hyperfunction.

PMID- 16970110
TI  - [Drug allergy assessed by modified Shelley's test. A case series].
AB  - BACKGROUND: The frequency of allergy to drugs is 5-10% in the general population,
      The Shelley's test is a method in vitro for its diagnosis and it is considered
      positive when it is equal o greater than 20%. OBJECTIVE: To show the allergy to
      drugs frequency evaluated by the Shelley's Modified Test. MATERIAL AND METHODS:
      We included 165 patients with clinical diagnosis of allergy to drugs to those who
      the test of Shelley's was applied modified test for one or several medicines. The
      study was made in the period of January 1st to December 3st 2002. RESULTS: 88%
      (145 patients) were positive, and 12% (20 patients) were negative in correlation
      with clinical findings. The female was more determinant (2:1 relation), with an
      average age of 45 years. The drugs that caused reactions of allergy in were the
      antibiotics (sulfas, penicillin, quinolones), analgesic (ASA, naproxen,
      diclofenac), antihypertensive (enalapril, captopril, verapamil) and others with
      95, 170, 48 and 97 cases respectively. The most frequent clinical features were
      urticaria, angioedema, anaphylactic shock and erythema. CONCLUSION: The Shelley's
      test is useful to support the diagnosis of allergy to drugs, although does not
      exclude it. The antibiotics intake is the most common cause and the most common
      clinical manifestation was urticaria.

PMID- 16970111
TI  - [Current and future approaches for the treatment of inflammatory diseases of
      inferior respiratory tract].
AB  - Among the allergic disorders we emphasize the inflammatory diseases of the
      inferior respiratory tract by their incidence, repercussion in daily activities,
      and by their high cost of medical attention. For their treatment, they require
      more than one inhaled or systemic drug. Current medicines tend to have adverse or
      secondary effects, such as: osteoporosis, type 3 diabetes mellitus, tremor or
      tachycardia. New medicines are being developed with less adverse or secondary
      effects, and much more selective and specific in the molecules involved in the
      allergic disease's physiopathology. Among them we find pascolizumab, which
      inhibits the differentiation made to Th2, as well as the citokines production.
      Other drugs are: mepolizumab, monoclonal antibody antiCD23, and the selective
      inhibitor of IgE (AJP13358) Rhu-Mab-E25. Currently, they are being developed some
      new drugs, such as SB-207499 (SKB) and LAS 31025, which are selective inhibitors
      of fosfodiesterase. Within the currently studied medicines that offer high
      specificity to inhibit the synthesis of interleukines we emphasize the presence
      of humanized monoclonal antibodies antireceptor IL-4. The anti IL-5 (SB-240563)
      is administered in asthmatic patients to reduce eosinofilia in expectoration.
      Tosilate of suplatast is a selective IL-4 and IL-5 inhibitor. Ramatroban (BAY or
      3405) is an antagonist of the tromboxane A2 receptor, which reduces the
      inflammatory process of the nasal mucose without hemodynamic effects.
      Immunotherapy with peptides avoids the response of IgE by the allergen, without
      mast cell degranulation.

PMID- 16970112
TI  - [Hypoacusis in pediatric patients with allergic rhinitis].
AB  - Currently, allergic disorders represent an important problem of public health.
      Besides having high prevalence they begin their clinical manifestations at early
      ages, in 75% of the cases before five years old. When they do not receive the
      proper treatment, they have systemic affectation, with a repercussion in the
      quality of life. The great comorbidity can cause a late and wrong diagnosis. In
      this article we review the relationship between hypoacusis and allergic rhinitis,
      with a description of their epidemiology, pathophysiology and clinical
      manifestations.

PMID- 16970113
TI  - [Macrolides. Antiinflammatory and immunomodulator effects. Indication in
      respiratory diseases].
AB  - This article reviews the basics and the clinical implications of the
      immunomodulatory effects of macrolides in different respiratory diseases. In
      addition to their antiinfective properties, some macrolides possess
      immunomodulatory effects (14 member ring). These macrolides have been used
      successfully to treat diffuse panbronchiolitis, a progressive inflamatory disease
      and may be very useful in the treatment of asthma, chronic bronchitis, chronic
      sinusitis, nasal polyps, otitis media with effusion, cystic fibrosis and
      bronchiectasis. We present the basic and clinical work supporting its chronic
      use. We will need future double blind controlled trials to determine the long
      term efficacy of macrolides for the treatment of chronic inflammatory airway
      diseases, as well as development of resistance, how to improve side effects ratio
      and the duration of effects after cessation of treatment.

PMID- 16970114
TI  - [Severe ovarian hyperstimulation syndrome treatment by decompressive paracentesis
      and self-transfusion of ascitis fluid].
AB  - BACKGROUND: The ovarian hyperstimulation syndrome is a serious complication in
      patients who undergo controlled ovarian stimulation and for that reason all
      clinicians who prescribe ovulation inducing agents must be prepared to recognize
      and manage ovarian hyperstimulation syndrome, to prevent severe and ocasionally
      mortal complications. OBJECTIVE: To communicate the experience in the treatment
      of ovarian hyperstimulation syndrome as a complication in patients who undergo
      controlled ovarian stimulation. PATIENTS AND METHODS: In the present study seven
      patients who developed severe ovarian hyperstimulation syndrome were included,
      and were treated by ultrasound guided paracentesis and self-transfusion of the
      ascitic fluid. RESULTS: In all patients we observed a clinical improvement
      immediately after the drainage of ascitic fluid no hematological or infectious
      disease were observed after the self-transfusion. We observed a reduction in
      hemoglobin of 20.9% and 22.2% in the hematocrit after paracentesis and self
      transfusion, meanwhile we observed an increase of 55.5% in the albumin level. Any
      patient developed hemodynamic disturbance after paracentesis after drainage of
      great volume in the paracentesis (mean of 4453.4 mL per patient). CONCLUSIONS:
      The drainage of ascitis by paracentesis and self-transfusion of the fluid is a
      good therapeutic option in patients with severe ovarian hyperstimulation syndrome
      in combination with intravenous fluids and administration of human albumin 25%.

PMID- 16970115
TI  - [Prevalence of urinary and anal incontinence in women from metropolitan area of
      Guadalajara].
AB  - BACKGROUND: Female urinary and anal incontinence are common entities in pelvic
      floor dysfunction. The most frequently age affected range from 45 to 69 years.
      Previous studies performed in the United States report a prevalence of 24-62% for
      urinary incontinence and 3-60% for anal incontinence. OBJECTIVE: To determine the
      prevalence of these disorders in the Guadalajara metropolitan area because we do
      not know it. PARTICIPANTS AND METHODS: A transversal and various stage study was
      performed recollecting blocks first, then houses, finally interviewing women and
      applying a structured questionnaire with somatometric and social-demographic data
      and also clinical-pathological antecedents. The data obtained was registered and
      processed first manually then using Excel and Epi-Info software. RESULTS: The
      group of women interviewed (n = 352) were between 15-85 years. The majority were
      married, housewives, 33% with grammar school, 23% finished high school, 25%
      professionists and 19% did not finish school; with an average of three
      pregnancies and with a body mass index (BMI) positive for overweight and obesity.
      The prevalence for urinary incontinence was 27.8% and anal incontinence of 3.4%.
      These are results compatible with those reported in the United States.
      CONCLUSIONS: Women living in Guadalajara have the same behavior that European and
      American women about prevalence of urinary incontinence. We recommend the
      performance of this type of studies in other states of this country in order to
      enrich the present information.

PMID- 16970116
TI  - [Random comparative study between intrauterine device Multiload Cu375 and TCu
      380a inserted in the postpartum period].
AB  - OBJECTIVE: To evaluate safety and effectiveness of the intrauterine device
      Multiload Cu375 compared with the TCu 380A inserted in the postpartum period.
      PATIENTS AND METHODS: In a randomized comparative study carried out in the
      National Perinatology Institute, intrauterine devices MLCu 375 and Tcu 380A were
      inserted to 157 patients who voluntary accepted, and previously signed informed
      consent. There were four instances for the intrauterine devices insertion: within
      10 minutes after vaginal delivery, during cesarean section (immediate
      postplacental insertion) and postpartum-postcesarean insertion (in the time range
      of 10 min to 48 h). All insertions were made with ring forceps. From 1 h to 24 h
      later, abdominal ultrasound examinations were performed to assess the distances
      between the upper part of the device to the fundus of uterine cavity. Follow up
      visits were scheduled at 3, 6, 9 and 12 months. Net cumulative life table event
      rates of discontinuations were estimated at one year. RESULTS: The expulsion
      rates were 10.4 for the MLCu 375 and 7.7 for the TCu 380A and they were not
      influenced by the moment of the intrauterine device insertion, not by the
      cervical dilatation, neither by the distance of the intrauterine device to the
      fundus of uterine cavity. The removal rates for bleeding and pain were 4.9 and
      4.8, the removal rates for non medical reasons were 3.7 and 4.9 respectively.
      There was one case of genital infection in the MLCu 375 group. There were no
      pregnancies, nor uterine perforation. The one year continuation rates were 77.1
      and 82.6 respectively. There were no statistical significant differences in the
      comparative rates. CONCLUSIONS: The intrauterine device MLCu 375 is as safe and
      effective as the TCu380A when they are inserted in the postpartum period.

PMID- 16970117
TI  - [Symptomatic profile in peri and postmenopausal women].
AB  - OBJECTIVE: To determine the symptoms that women refer during peri and
      postmenopause. PATIENTS AND METHOD: A cross-sectional study was carried out from
      April to December 2005; 500 women between 45 and 65 years old were included. We
      applied them the NR 1 questionnaire of symptoms for mature women. Data were
      obtained by means of a face-to-face interview. Results were analyzed through
      descriptive statistics, with percentage values, arithmetic mean and standard
      deviation. Differences between groups were evaluated with Student's T test, chi
      square test, and Fisher exact test. RESULTS: Perimenopausal women had higher
      levels of depression (p = 0.03). Postmenopausal women presented higher frequency
      of sleep disturbances (p = 0.003). We found that perimenopausal women had more
      night sweats (p = 0.005), excessive hot (p = 0.006), hot flashes (p = 0.001),
      headaches (p = 0.001), vaginal dryness (p = 0.03), and dyspareunia (p = 0.005).
      On the other hand, postmenopausal women presented higher frequency of changes in
      libido (p = 0.001). CONCLUSIONS: In general, perimenopausal women have more
      symptoms than posmenopausal women. It is advisable an exhaustive analysis of the
      perimenopausal women symptoms in order to offer them an integral substitutive
      treatment.

PMID- 16970118
TI  - [Assessment of the treatment with imiquimod in persistent infection by human
      papillomavirus with the polimerase chain reaction method].
AB  - BACKGROUND: Molecular studies have shown that oncogenic genotypes of human
      papillomavirus (HPV) are the main risk factor for cervical cancer development.
      Sub-clinical wound does not cause symptoms and is diagnosed by colposcopy or
      histology, in addition the latent infection is associated with the presence of
      DNA of the HPV, but when clinical and histological abnormalities are not
      presented only molecular techniques can detect this infection. OBJECTIVE: To
      determine if complementary processing with imiquimod, recent medicament with
      powerful antiviral activity in vitro as in vivo, reduces the cervical persistence
      of HPV. PATIENTS AND METHODS: This study was carried out with 87 patients, who
      had antecedents of HPV cervical and intraepithelial wound with low degree.
      Patients were divided as follows: treated with cryotherapy, cervical loop
      electrosurgical and imiquimod, all with diagnosis by cervical cytology,
      colposcopy and polymerase chain reaction (PCR) for HPV. At 3, 6 and 12 months
      after the processing, PCR, cervical cytology and colposcopy control were carried
      out again. RESULTS: Out of the 87 patients studied, 11% (10) patients treated
      with cervical cytology were positive for VPH; with colposcopy 8% (7) of patients
      and with PCR 40% (34) of patients; decreased persistence with combined methods of
      loop and imiquimod was obtained in 29% (5) patients; however, when utilized
      imiquimod alone, there were 55% (11) patients with persistence determined by PCR
      method. DISCUSSION: Imiquimod appears to be beneficial in 45% of the patients, in
      contrast with efficacy reported until 85% in genitals and annals warts, in
      addition, the capacity of eliminating the viruses has been shown, therefore it is
      possible that its potential effect could be observed long-time. It is evident
      that the percentages of viral detection are improved for PCR method, compared
      with indirect methods as cervical cytology and colposcopy, which is favorable
      when virus serotypes are of high degree of transformation and ablative methods
      should be conservatives due to fertility motives.

PMID- 16970119
TI  - [Present usefulness of diagnostic tests in hyperandrogenism].
AB  - There are diagnostic tests that allow to differentiate feminine hyperandrogenism
      of tumorous, non-tumorous, ovarian, adrenal and peripheral origin. We made a
      review of the current available tests accordingly to a case of amenorrhea and
      hyperandrogenism. By means of the low-dose dexamethasone suppression and human
      chorionic gonadotropin hormone (hCG) stimulation test we confirmed a suprarenal
      participation. There was spontaneous menses when treated with dexamethasone.

PMID- 16970121
TI  - [The way I study the fertility of a couple].

PMID- 16970122
TI  - [Minor surgery in obstetrics. 1951].

PMID- 16970120
TI  - [Discordant nuchal translucency in monochorionic twin pregnancy. A case report].
AB  - The twin-to-twin transfusion syndrome is a serious anomaly occurring from vessels
      anastomosis between the fetal-planetary circulations of monochorionic twin
      pregnancies with a high perinatal morbidity and mortality. In the first
      trimester, the presence of discordant increase of the nuchal translucency
      associated a reverse blood flow in the ductus venosus are marks of twin-to-twin
      transfusion syndrome. In this report, we related a case of monochorionic twin
      pregnancy in the first trimester in that the first diagnostic signal this
      syndrome was an increase of the measurement of nuchal translucency, associated
      the reverse blood flow in the ductus venosus of receiving fetus.

PMID- 16970123
TI  - [Comparative study of overactive bladder prevalence in patients younger than 50
      years with and without hyperprolactinemia].
AB  - OBJECTIVE: To determine if the hyperprolactinemia is associated with idiopathic
      overactive bladder. PATIENTS AND METHODS: We performed a transversal and analytic
      two groups study. We included all the patients whom plasma levels of prolactin
      were measured in the National Institute of Perinatology from March 1st to May 31,
      2005 and fulfilled the selection criteria. To all these patients we applied a
      questionnaire of eight questions for the overactive bladder diagnostic. We used
      chi square statistical technique to establish if hyperprolactinemia is associated
      with the overactive bladder. RESULTS: One hundred sixty years patients were
      studied, establishing a relative prevalence of 2.82 (IC 95%: 1.45-3.17),
      determining association between the variables. CONCLUSIONS: hyperprolactinemia is
      associated with overactive bladder.

PMID- 16970124
TI  - [Maternal and fetal morbidity related to delayed antenatal work incapacity].
AB  - OBJECTIVE: To determine if there is higher maternal fetal morbidity associated to
      delayed antenatal work incapacity. PATIENTS AND METHOD: A case-control study was
      carried out, including 220 pregnant workers. They were divided into 110 women who
      delayed their antenatal work incapacity (cases) and 110 women who took it on time
      (controls). Sociodemographic and clinical data, which included maternal fetal
      morbidity, were registered. Results were analyzed by percentage values and
      arithmetic mean. Differences between groups were evaluated with Student's t test,
      chi square test, or exact test of Fisher. An alpha value was set at 0.05.
      RESULTS: There were 48 (43.6%) women who had antenatal complications in the group
      of cases and 27 (24.5%) in the controls, p= 0.004. The most common complication
      in the cases was preterm labor (29.1%), and in the controls was threatening of
      spontaneous abortion (55.5%). Other significant variables were: higher maternal
      age in the cases group (32.2 vs 22.5 years, p < 0.001), and lower number of
      antenatal visits (8.2 vs 9.5, p < 0.001). CONCLUSIONS: We conclude that there is
      higher maternal morbidity in women who delayed their antenatal work incapacity.
      It is recommended to give this incapacity according to present normative.

PMID- 16970125
TI  - [Hyaline membrane disease: mortality and maternal and neonatal risk factors].
AB  - OBJECTIVE: To identify maternal and neonatal risk factors associated with hyaline
      membrane disease and its mortality. PATIENTS AND METHOD: A case-control study
      with 41 newborns with hyaline membrane disease and 123 controls was made between
      September 2001 and February 2002 in the Hospital Civil de Guadalajara Dr. Juan I.
      Menchaca. The diagnosis of hyaline membrane disease was done with clinical and
      radiographic data. Maternal risk factors were obtained by direct interview with
      the mother; the newborn data were obtained of the clinical files. The association
      was measured with the odds ratios (OR) and the confidence interval of 95%.
      RESULTS: The frequency of hyaline membrane disease was of 6.8 per 1,000 live
      births. Mortality rate was of 2.8 per 1,000 live births. There were 17 deaths
      (41%). The risk factors associated with hyaline membrane were: illness during the
      first and second trimester of pregnancy, (OR: 3.28 [1.16-9.31]; OR: 8.88 [3.56
      22.50], respectively), Apgar score lower than seven at the first minute (OR:
      18.57 [4.50-88.67]), and masculine gender (OR: 2.58 [1.15-5.83]). CONCLUSIONS:
      Frequency and mortality were similar to the reported by other studies made in
      population samples. The exposure to illnesses during pregnancy and the low Apgar
      score were associated with the increased frequency of hyaline membrane disease.

PMID- 16970126
TI  - [Therapeutic assessment of emergency cerclage. Analysis of a cases series].
AB  - BACKGROUND: Cervical incompetence is the incapacity of cervix to retain a
      pregnancy until term or until feasibility of the fetus. Patients present cervical
      enlargement without pain or contractions, vaginal strange sensation and membranes
      protrusion through most minimum degrees of enlargement. The cervical incompetence
      management can be rest in bed or cerclage. The emergency cerclage is carried out
      in patients with enlargement > or = 2cm with or without membranes prolapsus.
      OBJECTIVE: To evaluate the maternal and neonatal results of emergency cerclage
      with Espinosa-Flores modified technique in pregnancy from 13 to 28 weeks.
      PATIENTS AND METHODS: This series of cases was carried out as observational and
      prospective study, all patients with emergency cerclage and pregnancy from 13 to
      28 weeks with cervical incompetence were included, during period of January 2000
      to December 2003, in Gynecology and Obstetric Hospital from Medical Center La
      Raza, IMSS. Variables of study were gestational age at moment of cerclage,
      pregnancy prolongation, and maternal and neonatal complications. RESULTS: Ten
      patients were included, with age of 32.1 +/- 5.1 years. It was observed a mean
      prolongation of pregnancy 10 weeks after cerclage. The gestation was interrupted
      at 31.1 +/- 5.2 weeks. The most frequently complication was premature membranes
      rupture. Neonatal survival was 70%. CONCLUSIONS: The placement of emergency
      cerclage continuous being a therapeutic procedure to improve neonatal prognostic.
      The shortest prolongations of pregnancy were found in patients with greater
      enlargement (> or = 3cm) and who had membranes protrusion.

PMID- 16970127
TI  - [Antiphospholipid syndrome and pregnancy].
AB  - OBJECTIVE: To assess the maternal and perinatal outcome of patients with
      antiphospholipid syndrome in pregnancy. PATIENTS AND METHOD: A descriptive and
      retrospective analysis of patients with antiphospholipid syndrome in pregnancy
      was made from January 2000 to June 2005. RESULTS: We analyzed 35 patients.
      Primary and secondary antiphospholipid syndrome occurred in 25 (71%) and 10 (29%)
      women, respectively. Nine cases were associated with systemic lupus erythematosus
      and one with scleroderma. Approximately, 48% of women had history of thrombosis,
      23% recurrent pregnancy loss, and 15% early onset preeclampsia in previous
      pregnancies. Twenty-seven patients had positive anticardiolipin antibodies, 6
      lupus anticoagulant, and 2 both of them. About 80% of the patients were delivered
      by cesarean section. There was one spontaneous embryo loss before seven weeks.
      Eleven (32%) patients had preeclampsia. There were no maternal deaths. All women
      began treatment since the first trimester of pregnancy. Twenty-three patients
      (66%) received heparin and low dose aspirin, 8 cases (22%) heparin, low dose
      aspirin and prednisone, for presenting systemic lupus erythematosus, and the
      remaining 4 cases (12%) were treated with prednisone and aspirin. Ninety four
      percent of the cases got a live newborn. There were two neonatal deaths secondary
      to extreme prematurity and associated with preeclampsia. There was one fetal
      death related to maternal lupus renal activity. Fifty-eight percent of the
      newborns were premature. Intrauterine growth restriction was present in 20% of
      the cases. CONCLUSIONS: Early treatment combined with close maternal-fetal
      surveillance was associated with a 90% chance of a live birth rate. However,
      prematurity, preeclampsia and intrauterine growth restriction were common.

PMID- 16970129
TI  - [How the studies of the reproduction process contributed to the appearance of
      neuroendocrinology].
AB  - Geoffrey W. Harris, inspired by Francis H. Marshall, began the experimental
      studies in order to demonstrate a vascular connection between the hypothalamus
      and the adenohypophysis, with neuropeptides as messengers. This confirmed his
      theory that the mechanism consists in that the nerve fibers in the hypothalamus
      release hormonal substances in the capillaries of the primary plex in the medium
      eminence, and that these substances are carried by the vessels of the portal
      circulation to stimulate or inhibit the pars distalis cells of the hypophysis.
      This theory placed the hypothalamus as the fundamental structure to understand
      the link between the brain and the hypophysis. Later, it was known the structure
      of neurohormones, particularly the responsible for producing gonadotrophins. By
      this way, it was possible to go into the processes involved in reproduction. This
      was the origin of neuroendocrinology, gestated by investigations made in the
      reproduction of animals, including man. The purification, sequentiation and
      synthesis of the hormone that controls the FSH and LH production have allowed to
      study the physiology and disorders of the neuroendocrine circuit.

PMID- 16970128
TI  - [Normal reference values of the pulsatility index and peak systolic velocity in
      the fetal middle cerebral artery during normal pregnancy].
AB  - OBJECTIVE: To establish the normal reference values of the fetal middle cerebral
      artery (MCA) pulsatility index (PI) and MCA peak systolic velocity (PSV) during
      normal pregnancy. PARTICIPANTS AND METHODS: A total of 727 normally grown fetuses
      were evaluated with pulsed Doppler ultrasound between 20 and 40 weeks of
      gestation. The MCA was located in a transverse view of the fetal head 1 cm after
      its origin from the Willis vascular circle. The insonation angle was always kept
      as close as possible to 0. The PI and PSV were measured in 5 consecutive and
      uniform cardiac cycles and the mean considered as the representative for each
      case. Normal reference values for each gestational week were constructed.
      Reproducibility and agreement were analyzed for the MCA PI estimation. RESULTS:
      There was a significant correlation between MCA PSV and gestational age (GA) (PSV
      = -13.81+1.96 X GA, r2 = 0.59, p=0.001). The correlation between MCA PI and GA
      showed an initial increment until week 30 with a further reduction towards the
      end of the pregnancy (MCA PI = 2.44 + -0.02 X EG, r2 = 0.09). Reproducibility
      analysis of the MCA PI estimation showed an intra-class and inter-class
      correlation coefficients of 0.89 (95%CI 0.65-0.97) and 0.87 (95% CI 0.63-0.93),
      respectively. Agreement evaluation showed a mean difference between observers of
      0.03 (standard deviation 0.19), with 95% limits of agreement of -0.41 a 0.35.
      CONCLUSION: The normal reference values obtained in this study confirm the
      diagnostic and prognostic capacity of the fetal MCA PI and the MCA PSV evaluation
      in high risk pregnancies.

PMID- 16970130
TI  - [Heterotopic pregnancy].
AB  - The heterotopic pregnancy is a combination of an intra-uterine and extra-uterine
      pregnancy, at the same time. The spontaneous heterotopic pregnancy is a rare
      illness with an estimated frequency below one per 20,000 and one per 30,000. The
      first case was reported in France by Duverney in 1708 during an autopsy. The
      frequency of this pregnancy has increased with the implementation of assisted
      reproduction techniques. This paper is the report of a case of spontaneous
      heterotopic pregnancy seen at the Angeles Mexico Hospital. A 32 year old woman,
      gravida 1; dilatation and curettage was performed on 13th February because of a
      blighted ovum, a lot of products of conception were obtained. The patient was
      discharged the next day only with analgesics. She returns to the emergency room
      on February 16th with hypovolemic shock and acute abdomen. A normocitic
      normocromic anemia was found on the hematic biometry, the transvaginal ultrasound
      reported amount of blood in the cul-de-sac, echogenic adnexal mass, suggesting a
      gestational sac with embryo. An emergency laparotomy was used to perform a left
      cornual resection; the findings were 600 cc of hemoperitoneum and a left ruptured
      ectopic pregnancy. She had an uneventful postoperative course, and was discharged
      72 hours later without complications. Heterotopic pregnancy is a rare illness and
      must always be considered for the increase in pregnancy related with assisted
      reproduction techniques, although, it should be considered in a spontaneous
      pregnancy too.

PMID- 16970131
TI  - [Role of surgery in abortion. 1951].

PMID- 16970132
TI  - When should prophylactic anticoagulation begin after a hip fracture?

PMID- 16970133
TI  - Migraine prophylaxis: who, why, and how.
AB  - If a patient has frequent, severely debilitating migraine headaches, prophylactic
      treatment may help. Beta-blockers, tricyclic antidepressants, and anticonvulsants
      have the best evidence of efficacy; calcium channel blockers and nonsteroidal
      anti-inflammatory drugs are also popular because they are well tolerated and
      inexpensive. We review migraine treatment with emphasis on prophylaxis.

PMID- 16970134
TI  - Is digoxin a drug of the past?
AB  - Digoxin has been the cornerstone of the treatment of heart failure for more than
      2 centuries. Now that newer therapies have been introduced that reduce the
      mortality rate in heart failure and recent trials have failed to prove the same
      for digoxin, its use has significantly decreased. But a careful review of the
      multiple pharmacologic actions of digoxin and closer analysis of the results of
      recent trials suggest that digoxin may in fact continue to be an effective
      treatment for heart failure.

PMID- 16970135
TI  - Tending to the musculoskeletal problems of obesity.
AB  - When an overweight or obese patient complains of musculoskeletal problems such as
      knee or back pain, it may be an oversimplification to say that the excess weight
      caused the problem and that losing weight will solve it. Nevertheless, weight
      loss can help and is worthwhile for cardiovascular health and other reasons.

PMID- 16970137
TI  - Imaging's roles in acute pancreatitis.

PMID- 16970136
TI  - Newer antibiotics for serious gram-positive infections.
AB  - Four newer antibiotics are available to treat gram-positive bacterial infections
      that are resistant to traditional antibiotics and to vancomycin. They should
      preferably be used with the help of an infectious-disease consultant: specific
      therapy should be chosen on the basis of the bacteria involved, the site of
      infection, whether the patient has kidney or liver disease, other medications the
      patient is taking, and side effects that develop.

PMID- 16970138
TI  - Aspirin prevents stroke but not MI in women; vitamin E has no effect on CV
      disease or cancer.
AB  - Low-dose aspirin taken every other day helps prevent stroke in women aged 45
      years and older, but does not prevent a first myocardial infarction (MI) or
      cardiovascular death among healthy women. Women receive no benefit from alternate
      day vitamin E in the primary prevention of cardiovascular disease or cancer.
      These were the findings of the Women's Health Study, in which investigators
      followed 39,876 female health professionals over 10 years. The women were
      randomized to receive either 100 mg of aspirin or a placebo tablet every other
      day; they were also randomized to take 600 IU of vitamin E or a placebo capsule
      on the intervening days. No statistically significant differences were seen
      between the aspirin and placebo groups in the primary cardiovascular end point,
      which was the combined number of nonfatal MIs, nonfatal strokes, and
      cardiovascular deaths. Analysis of secondary cardiovascular end points revealed
      that aspirin use was associated with no significant effect on the number of total
      MIs, fatal MIs, and nonfatal MIs, and a nonsignificant decrease in cardiovascular
      mortality. However, aspirin users did experience significantly fewer strokes, in
      particular ischemic strokes. Vitamin E had very little impact on the primary
      prevention of both cardiovascular events and cancer.

PMID- 16970139
TI  - [Minocycline-induced lupus erythematodes].
AB  - We report the case of an 18-year-old woman with arthralgia and swelling of distal
      joints at hands and feet, photosensitive reaction, butterfly rash, fatigue,
      tachypnea and unspecific cardiac pain three months after beginning a treatment
      with minocycline for acne. Recurrence of symptoms at a higher intensity occurred
      within hours of reexposition with minocycline. The antinuclear antibody test was
      positive. After withdrawal of minocycline, the symptoms improved and minocycline
      induced lupus was diagnosed. In the Swissmedic and WHO adverse drug reaction
      databases 267 other cases of possible minocycline-induced lupus were identified.
      Typical clinical and laboratory features are arthralgia, arthritis, myalgia,
      increased transaminases and/or jaundice, unspecific symptoms like fatigue and
      fever, skin disorders and positive antinuclear antibodies.

PMID- 16970140
TI  - [Does running increase the risk of osteoarthritis?].
AB  - There is no doubt that the mean body weight of our population is continuously
      rising. In this context it is interesting to know that running--compared to
      cycling--results in a higher decrease of subcutaneous adipose tissue and has
      therefore a favourable influence on body weight. But public opinion still assumes
      that running provokes arthritis. This is used as a pretext against regular
      running training. In this overview we would like to show that running does not
      increase the risk of arthritis contrary to physical inactivity and overweight.
      Runners do not show a higher risk of developing joint arthritis on their lower
      extremities. However, frequency of arthritis is significantly higher in inactive
      and obese persons.

PMID- 16970141
TI  - [Multiple erosive osteoarthritis of the lumbar spine associated with a cystic
      node of L5].
AB  - Osteoarthritis of the spine can predominate on the zygapophyseal joints or on the
      discovertebral space. In this last localization, it can be characterized by
      superficial erosions or a cystic lesion into the vertebral body with
      densification of the vertebral end-plates and small osteophytes. We present the
      case of an 83 years-old woman with an erosive osteoarthritis at 3 levels of the
      lumbar spine associated with a large cystic node of L5, revealed by a low energy
      fall. The absence of fever, a history of tuberculosis, inflammation at the
      laboratory tests and the aspect of the CT scan allowed the avoidance of
      sophisticated or invasive explorations. Evolution was good with medical
      treatment, making unnecessary immobilization into a brace.

PMID- 16970142
TI  - [Intercostal tumors: diagnostic pitfalls].

PMID- 16970143
TI  - [Large water intake and its sequelae].

PMID- 16970144
TI  - [A rare cause of dyspnea on exertion. A 76-year-old retired woman].

PMID- 16970145
TI  - [CME-ECG 13/Solution].

PMID- 16970146
TI  - [On stressed bodies and broken down autos: Hans Selye (1907-1082) and the
      "General Adaptation Syndrome"].

PMID- 16970147
TI  - Hyponatremia: why it matters, how it presents, how we can manage it.
AB  - Hyponatremia is a common electrolyte disorder among hospitalized patients and has
      been associated with increased mortality. Most patients are asymptomatic, but
      many do present with symptoms, usually of a generalized neurologic nature. Based
      on medical history, physical examination (including volume-status assessment),
      and laboratory tests, patients can be classified as having either hypervolemic,
      euvolemic, or hypovolemic hyponatremia. Management depends on the speed of
      hyponatremia onset; its degree, duration, and symptoms; and whether there are
      risk factors for neurologic complications. The risks of overly rapid correction
      must be weighed against the benefits of treating hyponatremia. Traditional
      therapies have significant limitations. New agents that antagonize arginine
      vasopressin at the V2 receptor or both the V(1A) and V2 receptors show promise
      for treating hypervolemic and euvolemic hyponatremia, as they induce desired free
      water diuresis without inducing sodium excretion.

PMID- 16970148
TI  - Exercise-induced hyponatremia: causes, risks, prevention, and management.
AB  - Exercise-induced hyponatremia is most commonly associated with prolonged exertion
      during sustained, high-intensity endurance activities such as marathons or
      triathlons. In most cases, exercise-induced hyponatremia is attributable to
      excess free water intake, which fails to replete the sometimes massive sodium
      losses that result from sweating. The risk of hyponatremia can be lowered by
      strategies to ensure fluid balance during exercise by maintaining the proper
      volume and type of fluid intake. Treatment of exercise-induced hyponatremia is
      based on whether the patient is volume-depleted, euvolemic, or fluid-overloaded.
      Because therapy must be tailored to volume status, physicians must make this
      determination before initiating therapy. If hyponatremia is life-threatening,
      hypertonic saline may be warranted to increase sodium in the extracellular fluid
      compartment and restore the natural balance.

PMID- 16970149
TI  - The role of vasopressin in congestive heart failure.
AB  - Neurohormonal abnormalities contribute to the pathophysiology of congestive heart
      failure (CHF). Successful approaches to improving the prognosis of patients with
      CHF are based largely on therapeutic interruption of activated neurohormonal
      systems. The use of antagonists and inhibitors of the renin-angiotensin
      aldosterone and sympathetic nervous systems has significantly improved clinical
      outcomes in CHF. Excessive secretion of arginine vasopressin (AVP) has the
      potential for deleterious effects on various physiologic processes in CHF
      Inhibition of AVP through vasopressin receptor antagonist therapy is a
      potentially beneficial new therapeutic approach to CHF

PMID- 16970150
TI  - AVP receptor antagonists as aquaretics: review and assessment of clinical data.
AB  - The antidiuretic hormone arginine vasopressin (AVP) is primarily responsible for
      regulating osmotic and volume homeostasis of body fluids, largely through binding
      to vasopressin type 1A (V(1A)) and type 2 (V2) receptors. Increased AVP secretion
      leads to decreased free water excretion with resulting water retention, and can
      cause dilutional hyponatremia. A new class of medications known as AVP receptor
      antagonists induces free water diuresis without natriuresis or kaliuresis, an
      effect termed aquaresis. Numerous clinical trials show AVP antagonists to be
      effective at increasing free water excretion and serum sodium in patients with
      hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion
      or edema-forming states such as congestive heart failure and cirrhosis. This
      article reviews clinical trial data on the AVP antagonists in late development
      (lixivaptan, satavaptan, and tolvaptan) and recently approved for marketing
      (conivaptan).

PMID- 16970151
TI  - [Expression characteristics of mouse Catsper--the structural protein of sperm
      hyperactivation].
AB  - OBJECTIVE: To study the expression specificity in tissues of the Catsper and its
      expression rules, which is a specification channels in sperm and plays an
      important role in sperm hyperactivation. METHODS: The expression of Catsper in
      eight different tissues was examined by RT-PCR and immunohischemistry, the
      location of Catsper in sperm determined by immunofluorescence and the expression
      changes of Catsper analyzed in mice of different age groups. RESULTS: Catsper was
      expressed specifically in the testis and epididymis, and was mainly located in
      the principal piece of the sperm tail. Catsper gene expression was
      developmentally regulated with a direct correlation between Catsper expression
      and mouse sexual maturation. Catsper gene experssion was first detected at 3
      weeks of age and increased significantly till 6 weeks of age and then gradually
      to a stationary phase. CONCLUSION: Catsper expresses in the testis and
      epididymis, and its growth period and expression amount are closely related with
      the developmental stages of the mouse.

PMID- 16970152
TI  - [CAG repeats of DNA polymerase gamma in Chinese males and relationship of
      idiopathic male infertility to CAG repeats].
AB  - OBJECTIVE: To analyze the polymerase gamma(Polg) gene polymorphisms in Chinese
      idiopathic infertile males and evaluate the correlation of the polymorphisms with
      male infertility. METHODS: We conducted a study of Polg CAG repeats in the sperm
      or blood DNA of 55 asthenospermia patients, 57 oligospermia patients, 34
      azoospermia patients, and 104 controls with PCR and GeneScan. Phenotypic data
      were available in all the subjects, including semen parameters, and clinical
      profiles. RESULTS: The frequency of 10/not 10 CAG genotype in asthenospermia
      patients was higher than in the other groups, but with no significance.
      CONCLUSION: Our findings have shown for the first time that there exits an ethnic
      difference between Chinese and European males in the number of CAG repeats of
      Polg gene, and that 10/not 10 CAG genotype may affect sperm motility.

PMID- 16970153
TI  - [Effect of endogenous carbon monoxide on the smooth muscle function of dog penile
      corpus cavernosum in vitro].
AB  - OBJECTIVE: To study the effect of endogenous carbon monoxide (CO) on the smooth
      muscle function of the dog penile corpus cavernosum in vitro. METHODS: Tissue
      bioassay was used to measure the corpus cavernosum muscle contraction and
      relaxation. The production of CO was induced in the corpus cavernosum smooth
      muscle, and the effect of CO on the penile corpus cavernosum smooth muscle pre
      contracted by phenylephrine (PE) was determined. RESULTS: Chlorinous hemoglobin
      could relax the smooth muscle stripes pre-contracted by 10 micromol/L PE. A dose
      dependent relaxation was observed. The relaxation responses by 10 -100 micromol/L
      chlorinous hemoglobin were significant compared with the control group (P < 0.
      01). The pretreatment of the muscle stripes with ZnPP-IX or methylthioninium
      significantly reduced the relaxing effect of chlorinous hemoglobin (P < 0.01).
      CONCLUSION: The relaxing effect of endogenous CO on the smooth muscle of the
      penile corpus cavernosum depends on the concentration of endogenous CO. The
      underlying mechanism may involve the pathway from CO to cGMP production.

PMID- 16970154
TI  - [Distribution features of Gleason score and its relationship with clinical stages
      in 346 prostate cancer patients].
AB  - OBJECTIVE: To analyze the distribution features of Gleason score and evaluate the
      relationship between Gleason score and clinical stages in patients with prostate
      cancer. METHODS: Surveys were made of the inpatients with prostate cancer
      diagnosed by pathology from January 1992 to June 2005 in our hospital. Gleason
      score and clinical stages were determined on the basis of pathological
      examination and clinical data of the prostate cancer patients. The patients were
      divided into three groups (1992-1999, 2000-2002 and 2003-2005). The Chi-square
      test was used to evaluate the distribution and differences of Gleason score among
      the three groups. Spearman rank correlation was applied to the evaluation of the
      relationship between Gleason score and clinical stages. RESULTS: We found a
      statistically significant shift in the distribution of Gleason score (chi2 =
      17.703, P < 0.01), and a slight increase in the mean Gleason score. The
      proportion of moderately differentiated tumor increased (chi2 = 10.736, P <
      0.01). There was little change in the proportion of Gleason score 7, 8, 9 and 10
      (chi2 = 4.038, P > 0.05). Gleason score had a significant positive correlation
      with clinical stages in the 346 cases of prostate cancer (r = 0.452, P < 0.01).
      Significant difference was observed between Gleason score 2-6 and 7 or 8-10 (chi2
      = 8.786, P < 0.01, chi2 = 22.956, P < 0.01), but not between the latter 2 groups
      (chi2 = 0.787, P > 0.05) in prediction of organ-confined disease. CONCLUSIONS:
      Gleason score 7 shows the similar value to Gleason score 8-10 in predicting the
      progression of the disease. Gleason score was significantly correlated with
      clinical stages, which suggests that Gleason score is also an important indicator
      for the prognosis of prostate cancer.

PMID- 16970155
TI  - [Pathological changes in the testes of the rats with hypospadia induced by
      dichlorvos].
AB  - OBJECTIVE: To study the mechanism of dichlorvos leading to hypospadia of rats.
      METHODS: From the 12th to the 17th day of conception, 20 pregnant female rats
      (the experiment group) were given 10 mg/(kg x d) dichlorvos, while another 10
      (the control group) administered 1.5 ml 0.9% NaCl/day. Out of 88 male newborns of
      the 20 experimental mother rats, 22 had hypospadia, while out of the 33 male
      newborns of the 10 controls, none had the problem. Five hypospadia newborns from
      the experiment group and another 5 normal ones from the control group were raised
      to sexual maturity, and then their testes were excised and embedded in paraffin,
      and the tissue sections were analyzed by regular HE staining and SP
      immunohistochemical staining with Calretinin. RESULTS: HE staining showed that
      the number of Leydig cells in the testis tissues of the hypospadia rats decreased
      significantly compared with the normal ones, but no change was observed either in
      the number or in the morphology of the seminiferous tubules. Moreover, the
      Calretinin positive Leydig cells were reduced dramatically in the testes of the
      hypospadia rats. CONCLUSION: Pregnant female rats, when exposed to dichlorvos,
      may cause reduction of testis Leydig cells in their male offsprings. Thus the
      probable mechanism of rat hypospadia induced by dichlorvos may lie in the
      decrease of the testosterone level caused by damage to Leydig cells from
      dichlorvos toxicity.

PMID- 16970156
TI  - [Expression of "epithelial-mesenchymal transition" associated proteins in
      prostate cancer cell lines with different metastatic potentials and its
      significance].
AB  - OBJECTIVE: To determine the characteristics of epithelial-mesenchymal transition
      (EMT) in different human prostate cancer cell lines and explore the molecular
      mechanisms of bone metastatic potentials. METHODS: Expressions of E-cadherin, N
      cadherin and Vimentin in several prostate cancer cell lines (LNCaP, C4, C4-2,
      IF11, IA8, Du145 and PC-3) with different metastatic potentials were detected by
      Western blotting. RESULTS: There was remarkable difference in the expressions of
      E-cadherin, N-cadherin and Vimentin between these cell lines. As one of the
      adhesion associated proteins, E-cadherin was detected with high expression in
      LNCaP, C4, C4-2 and PC-3, whereas with a low expression in IF11, IA8 and Du145.
      However, as one of the mesenchymal proteins, N-cadherin was shown to be
      completely different from Vimentin expression profile in these cell lines.
      CONCLUSION: There is actual difference in the EMT phenotypes among cell lines
      with different metastatic potentials. LNCaP, C4, C4-2 and PC-3 are cells without
      EMT change, while IF11, IA8 and Du145 are positive for EMT. The expressions of
      EMT associated proteins play important roles in promoting and repressing the
      metastasis of prostate cancer.

PMID- 16970157
TI  - [Sleeve circumcision and preputioplasty with modified incision].
AB  - OBJECTIVE: To evaluate the sleeve circumcision and preputioplasty with modified
      incision for the treatment of patients with phimosis or redundant prepuce.
      METHODS: Five hundred and seventy-six patients with phimosis or redundant prepuce
      underwent operations of sleeve circumcision or preputioplasty with modified
      incision. The conventional incision was modified and changed into two opposite
      tortuous incisions. RESULTS: The operation with modified incision had the
      following advantages: less blood loss, slight postoperative edema, no secondary
      bleeding or infection, quick recovery and good appearance of the penis.
      CONCLUSION: The sleeve circumcision and preputioplasty with modified incision is
      an excellent therapeutic option for phimosis and redundant prepuce.

PMID- 16970158
TI  - [Correlation of total antioxidant capacity in seminal plasma with sperm motility
      of infertile men].
AB  - OBJECTIVE: To evaluate the correlation of total antioxidant capacity (TAC) in
      seminal plasma with sperm motility in infertile men, and explore the clinical
      significance of TAC in seminal plasma in male fertility. METHODS: One hundred and
      thirteen infertile men with normal sperm density were included in the experiment
      group and 28 fertile men in the normal control. The seminal parameter analysis
      was performed by computer-assisted semen analysis (CASA) system. Seminal plasma
      TAC was measured with spectroscopic analysis. RESULTS: Seminal plasma TAC was
      (14.37 +/- 8.45) U in the infertile men with normal sperm density and (19.82 +/-
      6.33) U in the fertile control. Compared with the fertile men, seminal plasma TAC
      in the experiment group was significantly lower (P < 0.01). There was significant
      correlation between seminal plasma TAC and sperm motility, grade a sperm (r =
      0.208, P < 0.05), grade (a + b) sperm (r = 0.231, P < 0.05), straightness (STR)
      (r = 0.200, P < 0.05), linearity (LIN) (r = 0.208, P < 0.05), curvilinear
      velocity (VCL) (r = 0.189, P < 0.05), straight line velocity (VSL) (r = 0.210, P
      < 0.05), average path velocity (VAP) (r = 0.215, P < 0.05), and beat cross
      frequency (BCF) (r = -0.248, P < 0.01). There was no significant correlation
      among the average motion degree (MAD), the amplitude of lateral head displacement
      (ALH) and wobbly (WOB). CONCLUSION: TAC in seminal plasma is closely related to
      male fertility, appropriate TAC provides a favourable environment for sperm
      swimming. The decreased level of TAC in seminal plasma may be one of the causes
      of male infertility. The analysis of TAC in seminal plasma may afford valuable
      evidence in exploring the mechanism of male infertility and in clinical
      medication.

PMID- 16970159
TI  - [Effect of sildenafil on nocturnal penile tumescence].
AB  - OBJECTIVE: To evaluate the efficacy of sildenafil on nocturnal penile tumescence
      (NPT). METHODS: Thirty-five patients with erectile dysfunction (ED), 28 cases of
      organic ED and 7 cases of psychogenic ED, were treated with sildenafil 100 mg
      before bedtime. The NPT of the patients was observed by using NEVA. RESULTS:
      Erectile function significantly improved in the 28 cases of organic ED (P <
      0.05), but not in the 7 cases of psychogenic ED (P > 0.05). CONCLUSION:
      Sildenafil can improve NPT of organic ED patients without sexual stimulation.

PMID- 16970160
TI  - [Comparison and evaluation of two methods for measuring acid phosphatase activity
      in seminal plasma].
AB  - OBJECTIVE: To compare the routine method and the kit method for the measurement
      of acid phosphatase activity in seminal plasma, and to explore the possibility of
      the kit method for routine measurement. METHODS: Seventy-nine seminal plasma
      samples were assayed by routine method and kit method respectively for acid
      phosphatase. One sample was detected 10 times for within-run analysis, and an
      other two were measured by both the methods once a day for 10 days for between
      run analysis. Acid phosphatase activities in another 10 seminal plasma samples
      collected at random were measured immediately or 30 min after dilution by two
      technicians, respectively. RESULTS: There were significant positive correlations
      between the acid phosphatase activities measured by routine and kit methods (r =
      0.745, P = 0.000). In the within-run assay, the coefficient of variation for the
      kit method (13.72%) was similar with that for the routine method (10.66%). But in
      the between-run assay, the coefficients of variation for the kit method (13.8%
      and 15.49%) were obviously lower than those for the routine method (24.43% and
      21.04%). Compared with the acid phosphatase activities in seminal plasma measured
      immediately after dilution, those measured after 30-min standing were notably
      lower for either of the methods (P < 0.05). However, there wasnt significant
      difference in the acid phosphatase activities detected by the routine method
      between the two technicians (P = 0.165). CONCLUSION: The kit method is superior
      and preferable to the routine method for the measurement of acid phosphatase in
      seminal plasma.

PMID- 16970161
TI  - [Transrectal ultrasound-guided ethanol sclerotherapy for Mullerian duct cyst
      accompanied with ejaculatory duct obstruction].
AB  - OBJECTIVE: To evaluate the efficacy and safety of transrectal ultrasound-guided
      ethanol sclerotherapy in the treatment of Mullerian duct cyst accompanied with
      ejaculatory duct obstruction. METHODS: Under the transrectal ultrasound guidance,
      3 cases of prostate Mullerian duct cyst were treated by 20 G needle puncture and
      ethanol injection, and closely followed up by ultrasonic monitored on follow-up
      examinations. RESULTS: All the cysts involuted completely 6 months after the
      treatment. Symptoms caused by ejaculatory duct obstruction were relieved in all
      the patients. No severe complications occurred. CONCLUSION: Transrectal
      ultrasound-guided ethanol sclerotherapy is an effective and safe method for the
      treatment of Mullerian duct cyst accompanied with ejaculatory duct obstruction.

PMID- 16970162
TI  - [Molida therapy in the out-patient department for patients with III B
      prostatitis].
AB  - OBJECTIVE: To study the therapeutic effect of Molida therapy in the out-patient
      department for patients with III B prostatitis. METHODS: One hundred and thirty
      six patients with II B prostatis accompanied with psychological disorder of
      different degrees were divided into two groups: Group A (68 cases), treated with
      routine drug and Molida therapy, and Group B (68 cases), treated with routine
      drug only. The therapeutic effects of the two groups were analyzed. RESULTS:
      After an 8-week treatment, the scores of self-feeling symptoms of SCL-90, SAS and
      SDS in Group A were 70.5 +/- 22.3, 18.7 +/- 8.5 and 21.4 +/- 9.0, respectively,
      significantly lower than those in Group B (P < 0.05) and the rates of efficacy
      and obvious efficacy in alleviating prostatodynia in Group A were 100% and 72.1%,
      respectively, both higher than in Group B (P < 0.05). CONCLUSION: Molida therapy
      in the out-patient department is useful in improving the psychological disorder
      and enhancing the therapeutic effect for patients with III B prostatitis.

PMID- 16970163
TI  - [Interventional effect of behaviour psychotherapy on patients with premature
      ejaculation].
AB  - OBJECTIVE: To investigate the interventional effect of comprehensive behaviour
      psychotherapy on the ejaculatory latency of premature ejaculation (PE) patients,
      sexual satisfaction of sexual partners, as well as its influence on the results
      of clinical treatment. METHODS: Ninety PE patients were randomly divided into a
      psychological intervention group (n = 45) and a control group (n = 45). Both
      groups were given medicine therapy, and the former also received comprehensive
      behaviour psychotherapy for 6 weeks. All the patients were assessed with the
      Chinese index of sexual function for PE and ejaculatory latency in the vagina,
      and the clinical efficacy was compared between the two groups. RESULTS: Before
      treatment, the ejaculatory latency in the vagina was (0.69 +/- 0.25) min and
      (0.71 +/- 0.19) min respectively in the intervention and the control groups, as
      compared with (5.87 +/- 0.59) min and (4.76 +/- 0.54) min before treatment, with
      significant difference (P < 0.01). In the intervention group, the scores in the
      control of ejaculatory reflex, the sexual satisfaction of the patients and their
      sexual partners and anxiety or depress in sexual activity in CIPE were higher
      than in the control group, with significant difference between the two groups (t
      = 2.12, 2.31, 2.01, 2.24, P < 0.05). The difference in the SAS score after
      therapy was of significance (P < 0.01). A month after treatment, the effectivity
      rates of the two groups were 82.9% and 30% respectively, and the difference was
      significant (P < .01). CONCLUSION: Comprehensive behaviour psychotherapy
      obviously adds to the clinical efficacy of drugs in the treatment of PE.

PMID- 16970164
TI  - [Analysis of an AZFc deletion family with natural transmission].
AB  - OBJECTIVE: To report a rare family of AZFc deletion with natural transmission and
      explore the potential mechanism by which identical microdeletions cause different
      phenotypes. METHODS: Chromosomal quantity and construction were detected by G
      band, Y-chromosomal microdeletions by multiple PCR amplification for 12 sequence
      tagged sites (STSs, and the single-nucleotide polymorphisms (SNPs) of the DAZL
      gene, the autosomal homologue of deleted-in-azoospermia (DAZ) gene by DNA
      sequencing. RESULTS: Chromosome analysis revealed a normal karyotype 46, XY in
      the father and both of his two sons and microdeletions of the full AZFc region
      were identical, including sY152, sY157, sY242, sY254, sY255, sY239 locus.
      However, the phenotypes of the affected patients were different: the father had
      normal fertility, but the sperm density of his two sons deteriorated age
      dependently, and the younger one suffered from left cryptorchidism. SNP analysis
      demonstrated that two polymorphisms in exon 2 and 3 of the DAZL gene were
      identical in both the father and his sons. CONCLUSION: Identical Y-chromosomal
      microdeletions causing different phenotypes in this family is not associated with
      the polymorphisms of DAZL gene and may be related to other genes or environmental
      factors.

PMID- 16970165
TI  - [Sexual function of men with symptomatic benign prostatic hyperplasia and effect
      of Tamsulosin].
AB  - OBJECTIVE: To study the sexual function of men with benign prostatic hyperplasia
      (BPH) with the lower urinary tract symptoms (LUTS) and the effect of Tamsulosin.
      METHODS: One hundred and ninety-two cases of BPH accompanied with typical LUTS
      were investigated using the International Prostate Symptom Score (IPSS), Quality
      of Life (QOL), International Index of Erectile Function 5 (IIEF-5) and measuring
      the flow rate of urine before treatment. The patients were randomly divided into
      two groups, the treatment group (n = 103) given Tamsulosin 0.2 mg, and the
      control group (n = 89) taking placebo once a day for 8 weeks. The influence of
      various factors on sexual function was analyzed before and after treatment.
      RESULTS: The mean scores of IPSS, QOL, Qmax and IIEF-5 were (20.20 +/- 6.81),
      (4.51 +/- 0.76), (9.60 +/- 8.79) ml/s and (9.80 +/- 8.62), respectively. The
      incidence of erectile dysfunction was 75% (144/192). There was statistically
      significant correlation between age and IPSS score (r = 0. 203, P < 0. 005) or
      IIEF-5 score (r = -0.571, P < 0.001) as well as between IPSS and IIEF-5 scores (r
      = - 0.312, P < 0.001). Various indexes were significantly improved after
      Tamsulosin treatment as compared with pre-treatment (P < 0.001) and placebo
      administration (P < 0.001), but no significant difference in various indexes was
      observed in the control group. CONCLUSION: Age and LUTS are dangerous factors for
      sexual function, and the severity of LUTS is closely related to the development
      of sexual dysfunction. Tamsulosin can at once improve the sexual function and the
      lower urinary tract symptoms of the BPH patients.

PMID- 16970166
TI  - [Carnitines and male reproduction].
AB  - Carnitines are important conditionally essential nutrients in the organism, with
      extensive physiological functions, and highly concentrated in the epididymis and
      sperm. Carnitines play an important role not only in initiating sperm motility,
      promoting sperm maturation and enhancing sperm fertilizing, but also in
      regulating Sertoli cell function, protecting sperm against oxidative damage,
      reducing apoptosis of spermatogenic cell and inhibiting sperm aggregation.
      Accordingly, the objective of this review is to summarize the multifunctional
      roles of carnitine in male reproduction.

PMID- 16970167
TI  - [Progress in leukocytospermia research].
AB  - Leukocytospermia is a most common cause of male infertility, but the
      distribution, origin and role of leukocytes in semen are still controversial.
      Some reports on leukocytospermia have indicated its negative effects on semen
      parameters and even in vitro fertilization (IVF). Recent literature has made it
      clear that the most deleterious effect of leukocytospermia is that the increased
      reactive oxygen species (ROS) may cause sperm damage, leading to significantly
      increased male infertility. The treatment and prevention of leukocytospermia have
      been proven of help for improving semen parameters.

PMID- 16970168
TI  - [Advances in the study of steroidogenic acute regulatory protein].
AB  - The steroidogenic acute regulatory (StAR) protein is an essential component in
      the regulation of steroid biosynthesis in adrenal and gonadal cells. The StAR
      protein has a high tissue specificity, located on the mitochondrial membranes of
      some relative cells. It regulates the transfer of cholesterin from extracellular
      into intracellular and plays a dominant role in steroidogenic synthesis. Recent
      studies have also shown that the transcription and expression of StAR are
      modulated not only through the cAMP-PKA dependent pathway, but also by multiple
      hormones and cytokines, which contributes to the regulation of cholesterin
      synthesis.

PMID- 16970169
TI  - [Progress on the detection techniques for DNA integrity of sperm].
AB  - Oxidative stress, deficiencies in natural processes such as chromatin packaging
      and abortive apoptosis are the main factors that lead to sperm DNA damage. The
      DNA integrity of sperm is essential for fertilization, as well as for the normal
      development of the blastocyst, embryo and child. There is increasing evidence
      that sperm DNA anomalies may lead to infertility, abortion, stillbirth, fathead
      and chromosomal diseases. The routine examination of semen can not identify
      subtle defects in sperm DNA, so several detection techniques have been developed
      for estimating the DNA (nuclear DNA/mitochondria DNA) integrity of sperm, which
      is considered to be a better marker of male fertility potential than conventional
      semen parameters. This review attempts at a detailed description of these
      detection techniques, including their principles, methods, steps and clinical
      application.

PMID- 16970170
TI  - [Clinical study on the treatment of male immune infertility by
      Huzhangdanshenyin].
AB  - OBJECTIVE: To investigate the efficacy of the Chinese medicine Huzhangdanshenyin
      on male immune infertility, and provide an effective therapy for this disease.
      METHODS: Ninety men with immune infertility were selected as the research
      subjects and randomly divided into two groups, 60 in the treatment group, treated
      by Huzhangdanshenyin, and the other 30 in the control, treated by prednisone,
      both for 3 months. The improvement of clinical symptoms, immunologic indexes
      (antisperm antibodies in serum and seminal plasma) and sperm indexes (semen
      liquefied duration, motility, viability, density and abnormal morphology rate)
      were observed and the results analyzed. RESULTS: The total antisperm antibody
      reversing ratio of the treatment group was higher than that of the control (P <
      0.01), especially the serum antisperm antibody reversing ratio. There were
      significant differences in the clinical cure rate and total validity rate between
      the treatment group and the control (P < 0.01). After the treatment, the markers
      of the clinical symptoms (P < 0.01), especially the serum antisperm antibody
      reversing ratio. There were significant differences in the clinical cure rate and
      total validity rate between the treatment group and the control (P < 0.01). After
      the treatment, the markers of the clinical symptoms were lower (P < 0.01), and
      the improvement of the clinical symptoms was better in the treatment group than
      in the control (P < 0.01), especially the symptoms of pain in the back and knees,
      distending and bearing-down sensation of the perineum and testis, hypersexuality
      and topalgias. Compared with pre-treatment, sperm motility and viability of the
      treatment group significantly improved (P < 0.01), and so did sperm density (P <
      0.05). However, there were no significant differences in sperm density, semen
      liquefied duration, abnormal morphology rate and pH (P > 0.05) before and after
      the treatment. CONCLUSION: The Chinese medicine Huzhangdanshenyin works more
      effectively than prednisone in the treatment of male immune infertility. It could
      improve the antisperm antibody reversing ratio, clinical symptoms and signs and
      ameliorate sperm indexes with no obvious advierse effects.

PMID- 16970171
TI  - [Chinese periodicals indexed in MEDLINE in 2006].
AB  - For the first time, the Chinese Ministry of Science and Technology published an
      analysis report of Chinese papers indexed in MEDLINE, which indicates that the
      Chinese government is paying more and more attention to the role of MEDLINE in
      the evaluation of scientific research. A total of 4 959 journals are listed in
      the Lists of Journals Indexed in MEDLINE (2006) published by National Library of
      Medicine, USA (NLM), of which 95 are published in China (including Hong Kong and
      Taiwan) and 2 another Chinese periodicals are published abroad. To familiarize
      MEDLINE to more medical researchers and to help them contribute to the journals
      indexed in MEDLINE, this article lists the top 10 Chinese medical institution
      whose published papers were indexed in MEDLINE in 2004 along with the Chinese
      periodicals indexed in MEDLINE in 2006. And the status of MEDLINE in China is
      briefly analyzed as well.

PMID- 16970173
TI  - Molecular mechanisms in membrane traffic at the neuronal synapse: role of protein
      lipid interactions.

PMID- 16970174
TI  - My adventures with genes from the fountain of youth.

PMID- 16970175
TI  - Genetic dissection of human blood pressure variation: common pathways from rare
      phenotypes.

PMID- 16970176
TI  - The role of phosphoinositide 3-kinase in human disease.

PMID- 16970177
TI  - Cell-to-cell communication in bacteria: a chemical discourse.

PMID- 16970178
TI  - Innate intracellular immunity to retroviruses.

PMID- 16970179
TI  - A discussion of the possible ways to improve the performance of silica monoliths
      using a kinetic plot analysis of experimental and computational plate height
      data.
AB  - Using kinetic plots to analyse the performance of some of the best silica
      monoliths found in the literature shows that the current generation of silica
      monoliths outperform particulate beds only in the high plate-number region
      (roughly N > 40000). The plots also reveal the existence of a so-called
      'forbidden region' wherein no existing chromatographic support seems to be able
      to operate. To investigate several possible approaches to intrude this forbidden
      region, computational fluid dynamics simulations of the flow field and band
      broadening characteristics of a simplified structural mimic of real silica
      monoliths were made for five different porosities (epsilon = 0.38, 0.49, 0.60,
      0.72, 0.86). It was found that entering the forbidden region will necessitate new
      synthesis methods, yielding either a strong improvement of the structural
      homogeneity (if assuming constant domain size conditions) or a decrease of the
      domain size (if assuming constant homogeneity conditions).

PMID- 16970180
TI  - Affinity monolith chromatography.
AB  - The combined use of monolithic supports with selective affinity ligands as
      stationary phases has recently given rise to a new method known as affinity
      monolith chromatography (AMC). This review will discuss the basic principles
      behind AMC and examine the types of supports and ligands that have been employed
      in this method. Approaches for placing affinity ligands in monoliths will be
      considered, including methods based on covalent immobilization, biospecific
      adsorption, entrapment, and the formation of coordination complexes. Several
      reported applications will then be presented, such as the use of AMC for
      bioaffinity chromatography, immunoaffinity chromatography, immobilized metal-ion
      affinity chromatography, dye-ligand affinity chromatography, and biomimetic
      chromatography. Other applications that will be discussed are chiral separations
      and studies of biological interactions based on AMC.

PMID- 16970181
TI  - Monolithic stationary phases for fast ion chromatography and capillary
      electrochromatography of inorganic ions.
AB  - The focus of this review is on current developments in monolithic stationary
      phases for the fast analysis of inorganic ions and other small molecules in ion
      chromatography (IC) and capillary electrochromatography (CEC), concentrating in
      particular on the properties of organic (polymer) monolithic materials in
      comparison to inorganic (silica-based) monoliths. The applicability of these
      materials for fast IC is discussed in the context of recent publications,
      including the range of synthesis and modification procedures described. While
      commercial monolithic silica columns already show promising results on current IC
      instrumentation, polymer-based monolithic stationary phases are currently
      predominantly used in the capillary format on modified micro-IC systems. However,
      they are beginning to find application in IC particularly under high pH
      conditions, with the potential to replace their particle-packed counterparts.

PMID- 16970182
TI  - Surface engineering of microchannel walls for protein separation and directed
      microfluidic flow.
AB  - The preparation of surfaces in microfluidic devices that selectively retain
      proteins may be difficult to implement due to the incompatibility of
      derivatization methods with microdevice fabrication techniques. This review
      describes recently reported developments in simple and rapid methods for
      engineering the surface chemistries of microchannels based on construction of
      press-fit microdevices. These devices are fabricated by placing a glass fiber on
      a PDMS film and pressing the film on a silicon wafer or a microscope slide that
      has been derivatized with octadecyltrichlorosilane (ODS). The film adheres to the
      slide and forms an elliptically shaped channel around the fiber. The combination
      of surface wettability of a hydrophilic glass microfiber and the surrounding
      hydrophobic microchannel surfaces directs a narrow boundary layer of liquid next
      to the fiber in order to bring the sample in contact with the separation media
      and results in selective retention of proteins. This phenomenon may be exploited
      to enable microscale separation applications since there are a wide variety of
      fibers available with different chemistries. These may be used to rapidly
      fabricate microchannels that serve as stationary phases for separation at a
      microscale. The fundamental properties of such devices are discussed.

PMID- 16970183
TI  - Recent applications of conductivity detection in capillary and chip
      electrophoresis.
AB  - The review provides a comprehensive survey of the recent applications of contact
      and contactless conductivity detection in capillary electrophoretic and chip
      electrophoretic analyses of a broad scale of compounds, from low-molecular-mass
      highly mobile small inorganic and organic ions, via medium-molecular-mass
      peptides and oligo- and polynucleotides up to high-molecular-mass biopolymers,
      proteins and nucleic acids fragments. The review presents also the recent
      developments in the construction of different types of conductivity detectors
      (detectors with galvanic contact of the sensing electrodes with the BGE and
      sample components, contactless conductivity detectors with capacitively coupled
      tubular and semitubular electrodes and combined conductivity/optical detectors)
      applied in the capillary electromigration methods performed in classical fused
      silica, polytetrafluorethylene, and polyetheretherketone capillaries or on glass
      and polymethylmethacrylate microchips. In addition, the principle and theoretical
      bases of conductivity detection in capillary electromigration techniques, zone
      electrophoresis, ITP, micellar EKC, and electrochromatography are briefly
      described.

PMID- 16970184
TI  - Column selectivity for two-dimensional liquid chromatography.
AB  - Selectivity of phase system is of primary concern when designing a 2-D
      separation, as it affects the 2-D system orthogonality and consequently the peak
      capacity controlling the number of peaks that can be separated in the available 2
      D retention space limited by the time of analysis. Possibilities for
      characterization of LC phase system selectivity with respect to different polar
      and nonpolar structural units are compared, with special attention to
      multidimensional samples with various types of repeat groups, such as
      homopolymers, (co)polymers, fatty acid esters with various acyl lengths and
      number and position of double bonds, etc. Possibilities of the 2-D LC separations
      of these and other sample types, including pharmaceuticals, natural phenolic
      compounds, biopolymers, etc., using various combinations of separation modes are
      reviewed. Rules for design of comprehensive 2-D LC x LC systems are discussed,
      with respect to mobile phase compatibility in the two systems and modulation
      techniques suppressing band broadening connected with the sample fraction
      transfer from the first to the second dimension. Pitfalls connected with online
      connection of normal-phase and RP LC systems and their possible practical
      solutions are addressed and illustrated by practical examples.

PMID- 16970185
TI  - Hydrophilic interaction chromatography.
AB  - Separation of polar compounds on polar stationary phases with partly aqueous
      eluents is by no means a new separation mode in LC. The first HPLC applications
      were published more than 30 years ago, and were for a long time mostly confined
      to carbohydrate analysis. In the early 1990s new phases started to emerge, and
      the practice was given a name, hydrophilic interaction chromatography (HILIC).
      Although the use of this separation mode has been relatively limited, we have
      seen a sudden increase in popularity over the last few years, promoted by the
      need to analyze polar compounds in increasingly complex mixtures. Another reason
      for the increase in popularity is the widespread use of MS coupled to LC. The
      partly aqueous eluents high in ACN with a limited need of adding salt is almost
      ideal for ESI. The applications now encompass most categories of polar compounds,
      charged as well as uncharged, although HILIC is particularly well suited for
      solutes lacking charge where coulombic interactions cannot be used to mediate
      retention. The review attempts to summarize the ongoing discussion on the
      separation mechanism and gives an overview of the stationary phases used and the
      applications addressed with this separation mode in LC.

PMID- 16970186
TI  - Elevated temperature and temperature programming in conventional liquid
      chromatography--fundamentals and applications.
AB  - Temperature, as a powerful variable in conventional LC is discussed from a
      fundamental point of view and illustrated with applications from the author's
      laboratory. Emphasis is given to the influence of temperature on speed,
      selectivity, efficiency, detectability, and mobile phase composition (green
      chromatography). The problems accompanying the use of elevated temperature and
      temperature programming in LC are reviewed and solutions are described. The
      available stationary phases for high temperature operation are summarized and a
      brief overview of recent applications reported in the literature is given.

PMID- 16970187
TI  - Fast analysis in liquid chromatography using small particle size and high
      pressure.
AB  - In order to enhance chromatographic performances in terms of efficiency and
      rapidity, LC has recently evolved in the development of short columns packed with
      small particles (sub-2 microm) working at high pressures (> 400 bar). This
      approach has been described 30 years ago according to the fundamental
      chromatographic equations. However, systems and columns compatible with such high
      pressures have been introduced in the market in 2004 only. Advantages of small
      particles working at high pressure will be discussed in terms of sensitivity,
      efficiency, resolution, and analysis time. Potential problems encountered with
      high pressure in terms of frictional heating and solvent compressibility will
      also be discussed even if systems working at a maximum pressure of 1000 bar are
      not influenced by these parameters and give reliable and reproducible results.
      Several applications will highlight the potential and interest of this new
      technology.

PMID- 16970188
TI  - Urea bonded cyclodextrin derivatives onto silica for chiral HPLC.
AB  - Several structurally well-defined perfunctionalised cyclodextrin chiral
      stationary phases (CD CSPs) for high performance liquid chromatography have been
      successfully prepared by immobilisation of perfunctionalised cyclodextrins on
      silica through urea linkage(s) using the Staudinger reaction. These CSPs show
      high chiral recognition efficiency and are utilised in the resolution of various
      types of racemic compounds. This paper reviews the development of sixteen
      perfunctionalised cyclodextrin-based CSPs, their preparation, and their
      application to enantioseparation of seventy-seven racemic compounds under a range
      of separation conditions.

PMID- 16970189
TI  - Applications of nanomaterials in liquid chromatography: opportunities for
      separation with high efficiency and selectivity.
AB  - During recent decades, great efforts have been made to improve the chemical
      stability, selectivity, and separation efficiency of stationary phases in liquid
      chromatography. Significant progress has been achieved, especially after the
      introduction of nanomaterials into separation science. This review covers the
      applications of nanomaterials playing various roles in liquid chromatography.
      Future possibilities for developing nanomaterial-based stationary phases are also
      discussed.

PMID- 16970190
TI  - Chromatographic analysis of penicillins in pharmaceutical formulations and
      biological fluids.
AB  - Natural penicillin (benzylpenicillin) is the oldest antibiotic observed by
      Alexander Fleming in 1928. To broaden its spectrum of activity, natural
      penicillin was modified, giving rise to a group of antibiotics under the name
      'penicillins'. Although an increasing number of bacteria appear to be resistant
      to them, penicillins are used to treat a variety of bacterial infections
      including Gram-positive, Gram-negative aerobic and anaerobic bacteria.
      Consequently, they are widely used in human and veterinary medicine to prevent
      and treat diseases. This review covers the analytical methodologies, mainly
      chromatographic, employed to the penicillins determination in pharmaceutical
      formulations, biological fluids and in production-scale fermentations reported in
      the literature. Results of published assays are comparatively presented focusing
      on sample preparation regarding isolation and purification, chromatographic
      conditions and method validation. Information on chemical structure, spectrum of
      activity and action mechanism of common penicillins has also been given.

PMID- 16970191
TI  - Detector technologies for comprehensive two-dimensional gas chromatography.
AB  - The detector is an integral and important part of any chromatographic system. The
      chromatographic peak profiles (i.e. peak separation) should, ideally, be
      unaffected by the detector--it should only provide the sensing capacity required
      at the end of a column separation process. The relatively new technique of
      comprehensive 2-D GC (GC x GC) extends the performance of GC manyfold, but comes
      at a price--existing GC systems may not be adequately designed with the
      requirements of GC x GC in mind. This is primarily the need for precise
      measurement of very fast peaks entering the detector (e.g. as fast as 50 ms
      basewidth in some instances). The capacity of the detector to closely track a
      rapidly changing chromatographic peak profile depends on a number of factors,
      such as design of flow paths and make-up gas introduction, type of detector
      response mechanism, and the chemistry of the response. These factors are
      discussed here as a means to appreciate the technical demands of detection in GC
      x GC. The MS detector will not be included in this review.

PMID- 16970192
TI  - Acoustic methods of detection in gas chromatography.
AB  - A brief review of the use of acoustic detection methods in GC is presented. While
      a number of methods (some quite similar) have been developed for use as gas-phase
      sensors in various applications, this article focuses specifically on those
      techniques that have been used to detect analytes following their separation by
      GC. Overall, a number of "active" acoustic methods (which measure analytes
      through their interaction with a controlled external acoustic wave source) were
      reportedly used as GC detectors. These include ultrasonic, thickness shear mode,
      surface acoustic wave (SAW), and flexural plate wave methods. Conversely,
      "passive" acoustic methods (those that produce an acoustic signal through some
      chemical reaction with the analyte) have also been used as GC detectors. These
      include photoacoustic and acoustic flame methods of detection. Of the two major
      classifications, reports of active methods are far more prevalent. In particular,
      the usage of SAW techniques with GC is an area of research that has seen
      accelerated growth in recent years.

PMID- 16970193
TI  - Unique selective detectors for gas chromatography: nitrogen and sulfur
      chemiluminescence detectors.
AB  - Many of present day's complex analyses and challenging analytical tasks demand
      highly selective detection techniques for GC. Universal nitrogen/sulfur
      chemiluminescence detection is one of the most powerful analytical tools for gas
      chromatographic analysis. Its strength stems from the unique and beneficial
      characteristics of high selectivity, sensitivity, and equimolarity. The
      nitrogen/sulfur chemiluminescence detection technology has provided analytical
      solutions unsurpassed by any other techniques to a broad range of applications in
      petroleum characterization, food/beverage flavor analysis, and environmental
      monitoring. This paper presents a general review of this unique technology,
      including a brief description of operating principles, an overview of detector
      performance, practical discussions on instrument operation, and a sizable list of
      applications.

PMID- 16970194
TI  - Isotope-ratio detection for gas chromatography.
AB  - Instrumentation and methods exist for highly precise analyses of the stable
      isotopic composition of organic compounds separated by GC. The general approach
      combines a conventional GC, a chemical reaction interface, and a specialized
      isotope-ratio mass spectrometer (IRMS). Most existing GC hardware and methods are
      amenable to isotope-ratio detection. The interface continuously and
      quantitatively converts all organic matter, including column bleed, to a common
      molecular form for isotopic measurement. C and N are analyzed as CO2 and N2,
      respectively, derived from combustion of analytes. H and O are analyzed as H2 and
      CO produced by pyrolysis/reduction. IRMS instruments are optimized to provide
      intense, highly stable ion beams, with extremely high precision realized via a
      system of differential measurements in which ion currents for all major
      isotopologs are simultaneously monitored. Calibration to an internationally
      recognized scale is achieved through comparison of closely spaced sample and
      standard peaks. Such systems are capable of measuring 13C/12C ratios with a
      precision approaching 0.1 per thousand (for values reported in the standard delta
      notation), four orders of magnitude better than that typically achieved by
      conventional "organic" mass spectrometers. Detection limits to achieve this level
      of precision are typically < 1 nmol C (roughly 10 ng of a typical hydrocarbon)
      injected on-column. Achievable precision and detection limits are correspondingly
      higher for N, O, and H, in that order.

PMID- 16970196
TI  - Flagging early examples of ambiguity I.

PMID- 16970195
TI  - A report on the Comprehensively Coupled Chromatography Conference (4C)--Riva del
      Garda--with a view to China, June 2007. The 29th ISCC symposium, Riva Del Garda,
      29 May - 2 June 2006 & 3rd Comprehensive Two-Dimensional Gas Chromatography
      Symposium, 28-30 May 2006.

PMID- 16970197
TI  - Surface assignment modulates object formation for visual short-term memory.
AB  - Recent results have suggested that the operational units of visual short-term
      memory (VSTM) are whole objects, rather than features or the total amount of
      information to be remembered. Here, for the first time, the influence of surface
      assignment on object formation for VSTM was investigated. The observers had to
      memorize the features of four briefly presented (300 ms) two-part objects,
      followed by a mask and a cue indicating which object to report on. The
      experiments contrasted whether there were any apparent depth differences between
      the two parts of each object, and whether observers had to report on only one or
      both features of the post-cued target object. Depth differences induced with
      stereoscopic disparity, and with a pictorial depth cue (simple interposition of
      object features), interfered strongly with performance when both features of an
      object needed to be memorized, but aided performance when only a single feature
      needed to be remembered. Furthermore, there was considerable within-feature
      interference consistent with some previous findings, but contradicting others.
      The potential implications for conceptions of VSTM are discussed in the light of
      two hypothesized stages: an early feature-based stage, as well as a higher-level
      object-based stage where the depth manipulations exert their effects. The results
      argue for a strong modulatory influence of surface assignment on object formation
      for a VSTM task.

PMID- 16970198
TI  - Who owns the contour of a visual hole?
AB  - Holes are useful in the study of shape, contour curvature, and border ownership.
      Several authors have suggested that holes have figural or quasi-figural status. I
      discuss three criteria to test the evidence that holes behave more like figures
      than like ground: (i) holes perceived as such; (ii) similar performance for holes
      and figures; (iii) different performance for holes and other ground regions.
      Using these criteria, I review the literature and conclude that holes do not have
      figural status in relation to border ownership. I also argue that holes are ideal
      stimuli to study figure-ground organisation.

PMID- 16970199
TI  - Active steering along corrugated surfaces.
AB  - A study is reported of the effect of dynamic occlusion that arises during
      locomotion over corrugated surfaces and its facilitating role on the control of
      locomotion, especially in cluttered environments. Surfaces varied in degree of
      corrugation and type of texture. Heading accuracy was assessed by having
      participants perform an active steering task. Results demonstrated the advantage
      of texture-mapped image surfaces over discrete element surfaces in the corrugated
      conditions. Observers appear to exploit accretion and deletion of optical texture
      at the occluding edge to extract and use information about heading direction for
      the control of movements in cluttered environments.

PMID- 16970201
TI  - A haptic face-inversion effect.
AB  - We examined whether a face-inversion effect occurs when participants explore
      faces by touch. We used a haptic version of the inversion paradigm with 3-D clay
      facemasks and non-face control objects (teapots) moulded from real objects.
      Young, neurologically intact, blindfolded participants performed a temporally
      unconstrained haptic same/different task in each of four stimulus conditions:
      upright facemasks, inverted facemasks, upright teapots, and inverted teapots.
      There was a significant inversion effect for faces in terms of accuracy, but none
      for teapots. The results are considered in terms of the consequences of
      sequential manual exploration for haptic face processing.

PMID- 16970200
TI  - Self recognition versus recognition of others by biological motion: viewpoint
      dependent effects.
AB  - We investigated the influence of viewing angle on performance in recognising the
      identity of one's own person and familiar individuals such as friends or
      colleagues from walking patterns. Viewpoint-dependent recognition performance was
      tested in two groups of twelve persons who knew each other very well.
      Participants' motion data were acquired by recording their walking patterns in
      three-dimensional space with the use of a motion capture system. Size-normalised
      point-light displays of biological motion of these walking patterns, including
      one's own, were presented to the same group members on a computer screen in
      frontal view, half-profile view, and profile view. Observers were requested to
      assign the person's name to the individual gait pattern. No feedback was given.
      Whereas recognition performance of one's own walking patterns was viewpoint
      independent, recognition rate for other familiar individuals was better for
      frontal and half-profile view than for profile view. These findings are discussed
      in the context of the theory of common coding of motor and visual body
      representations.

PMID- 16970202
TI  - Dependence of illusory motion on directional consistency in oblique components.
AB  - Pinna and Brelstaff (2000 Vision Research 40 2091-2096) reported a motion
      illusion on viewing two concentric circles consisting of quadrangular components
      with black and white sides on a grey background. Our results suggest that the
      illusion is based on the integration of motion signals derived from oblique
      components, and on the consistency in the direction among those components.
      Furthermore, arrays of these oblique components can elicit the perception of
      motion not only for the oblique components themselves, but also for other objects
      in the picture. We propose that the motion illusion depends not only upon
      detection of the illusory motion signal at each local oblique component, but also
      upon the accumulation of the signal all over the stimulus configuration.

PMID- 16970203
TI  - Spatiotemporal balance in competing apparent motion is not predicted from the
      strength of the single-motion percept.
AB  - Apparent motion is useful for investigating how spatiotemporal cues are
      integrated to determine the identity of a moving object. To examine its
      spatiotemporal properties, a competing-motion paradigm has advantages in strict
      psychophysical evaluation, despite difficulty in object-identity determination,
      over a non-competing subjective-grading paradigm. The latter has been often used,
      whereas the former has not been fully investigated. Here, we compared these two
      paradigms. In the competing-motion experiment, a sample spot was followed by a
      far and a near test spot with onset asynchrony. We found that the onset
      asynchrony between the near and far test spots was directly related to the
      distance ratio between them. This spatial size-invariant relation was not
      predicted from the strength of the single-apparent-motion percept, estimated from
      the non-competing subjective-grading experiment in which a sample spot was
      followed by only one test spot. Moreover, the spatiotemporal balance in competing
      apparent motion was found not to be valid under negative interstimulus-interval
      conditions, although a single apparent motion is perceived in those conditions.
      These clear discrepancies suggest that competing and single apparent motions are
      processed in a different way according to the difficulty in object
      identification.

PMID- 16970204
TI  - Background stripes affect apparent speed of rotation.
AB  - A gray line that rotated about its own center against a stationary background of
      vertical stripes appeared to double in perceptual speed as it rotated through the
      vertical position and thus momentarily aligned with the background. Four factors
      may contribute to this speed-up: (i) landmarks, in which the tip of the moving
      vertical line moves horizontally across the maximum number of stationary stripes;
      (ii) orientation repulsion of the moving line by the vertical stripes, which may
      distort the line's perceived position and hence its perceived speed; (iii) the
      orientation of an induced brightness pattern along the line; and (iv) the motion
      of the induced brightness pattern, which moves physically most rapidly along the
      line when the line is near vertical. To test these possibilities, an annulus
      display provided landmarks but no intersections, and this almost abolished the
      effect. A rotating-slit display provided an oriented, moving pattern that
      mimicked the induced brightness but had no landmarks, and this increased the
      effect. We conclude that the motion, but not the orientation, of the
      intersections [option (iv)] was responsible for the illusion. The fact that this
      motion along the length of the line affected the perceived speed of the line
      orthogonal to its own length indicates a failure on the part of the visual system
      to fully decouple tangential from radial motion.

PMID- 16970205
TI  - Can subthreshold summation be observed with the Ehrenstein illusion?
AB  - Subthreshold summation between physical target lines and illusory contours
      induced by edges such as those produced in the Kanizsa illusion has been reported
      in previous studies. Here, we investigated the ability of line-induced illusory
      contours, using Ehrenstein figures, to produce similar subthreshold summation. In
      the first experiment, three stimulus conditions were presented. The target line
      was superimposed on the illusory contour of a four-arm Ehrenstein figure, or the
      target was presented between two dots (which replaced the arms of the Ehrenstein
      figure), or the target was presented on an otherwise blank screen (control).
      Detection of the target line was significantly worse when presented on the
      illusory contour (on the Ehrenstein figure) than when presented between two dots.
      This result was consistent for both curved and straight target lines, as well as
      for a 100 ms presentation duration and unlimited presentation duration.
      Performance was worst in the control condition. The results for the three
      stimulus conditions were replicated in a second experiment in which an eight-arm
      Ehrenstein figure was used to produce a stronger and less ambiguous illusory
      contour. In the third experiment, the target was either superimposed on the
      illusory contour, or was located across the central gap (illusory surface) of the
      Ehrenstein figure, collinear with two arms of the figure. As in the first two
      experiments, the target was either presented on the Ehrenstein figure, or between
      dots, or on a blank screen. Detection was better in the dot condition than in the
      Ehrenstein condition, regardless of whether the target was presented on the
      illusory contour or collinear with the arms of the Ehrenstein figure. These three
      experiments demonstrate the ability of reduced spatial uncertainty to facilitate
      the detection of a target line, but do not provide any evidence for subthreshold
      summation between a physical target line and the illusory contours produced by an
      Ehrenstein figure. The incongruence of these results with previous findings on
      Kanizsa figures is discussed.

PMID- 16970206
TI  - Domestic chicks perceive stereokinetic illusions.
AB  - Stereokinetic illusions occur when certain 2-D patterns are set in slow rotation
      in a plane perpendicular to the line of sight. Such phenomena have never been
      investigated in animal species other than our own. We used the domestic chick
      (Gallus gallus) to check whether these illusions are experienced by non-human
      species, taking advantage of filial imprinting. Newly hatched visually naive
      chicks were individually exposed for 4 h to 2-D stimuli producing, to a human
      observer, the perception of a stereokinetic cone (experiment 1) or of a
      stereokinetic cylinder (experiment 2). Thereafter, each chick underwent a free
      choice test between a solid 3-D cone and a solid 3-D cylinder. A control group of
      newly hatched but not imprinted chicks underwent the same testing procedure, to
      check for the presence of any spontaneous preference for one or other of the two
      solid objects. Imprinted chicks approached the 3-D stimulus closely resembling
      the stimulus they had been exposed to during imprinting (the cone in experiment 1
      and the cylinder in experiment 2). Non-imprinted chicks did not show any
      preference. These results suggest that domestic chicks experience stereokinetic
      illusions.

PMID- 16970207
TI  - The bar-cross-ellipse illusion: alternating percepts of rigid and nonrigid motion
      based on contour ownership and trackable feature assignment.
AB  - We present a new multistable stimulus generated by continuously rotating an
      ellipse behind four fixed occluders. Despite the stimulus remaining constant,
      observers can alternate between one of four percepts: (1) a continuously morphing
      cross; (2) two independent perpendicular bars oscillating in depth; (3) a rigidly
      rotating ellipse observed behind the occluders; (4) a fixed cross observed
      through a continuously rotating, elliptical aperture. Interestingly, the initial
      percept naive observers tend to see is percept 1, which is the only nonrigid
      motion percept. This appears to be a violation of the hypothesized 'rigidity
      heuristic' in which rigid motion percepts tend to be perceived over retinally
      equivalent nonrigid ones. Here, we describe the relationships between each of the
      percepts and the assignment of contour ownership and figure/ground segmentation.

PMID- 16970208
TI  - Ring lesions of the brain.

PMID- 16970209
TI  - Prevention of catheter and intravascular device-related infections: a quality-of
      care mandate for institutions and physicians.

PMID- 16970210
TI  - Strep throat over and over: how frequent? How real?

PMID- 16970211
TI  - Minimally conscious state vs. persistent vegetative state: the case of Terry
      (Wallis) vs. the case of Terri (Schiavo).

PMID- 16970212
TI  - The risk of bloodstream infection in adults with different intravascular devices:
      a systematic review of 200 published prospective studies.
AB  - OBJECTIVE: To better understand the absolute and relative risks of bloodstream
      Infection (BSI) associated with the various types of intravascular devices
      (IVDs), we analyzed 200 published studies of adults In which every device in the
      study population was prospectively evaluated for evidence of associated infection
      and microbiologically based criteria were used to define IVD-related BSI.
      METHODS: English-language reports of prospective studies of adults published
      between January 1, 1966, and July 1, 2005, were identified by MEDLINE search
      using the following general search strategy: bacteremla [Medical Subject Heading,
      MeSH] OR septicemia [MeSH] OR bloodstream Infection AND the specific type of
      intravascular device (e.g., central venous port). Mean rates of IVD-related BSI
      were calculated from pooled data for each type of device and expressed as BSIs
      per 100 IVDs (%) and per 1000 IVD days. RESULTS: Point incidence rates of IVD
      related BSI were lowest with peripheral Intravenous catheters (0.1%, 0.5 per 1000
      IVD-days) and midline catheters (0.4%, 0.2 per 1000 catheter-days). Far higher
      rates were seen with short-term noncuffed and nonmedicated central venous
      catheters (CVCs) (4.4%, 2.7 per 1000 catheter-days). Arterial catheters used for
      hemodynamic monitoring (0.8%, 1.7 per 1000 catheter-days) and peripherally
      inserted central catheters used in hospitalized patients (2.4%, 2.1 per 1000
      catheter-days) posed risks approaching those seen with short-term conventional
      CVCs used in the Intensive care unit. Surgically implanted long-term central
      venous devices--cuffed and tunneled catheters (22.5%, 1.6 per 1000 IVD-days) and
      central venous ports (3.6%, 0.1 per 1000 IVD-days)--appear to have high rates of
      Infection when risk Is expressed as BSIs per 100 IVDs but actually pose much
      lower risk when rates are expressed per 1000 IVD-days. The use of cuffed and
      tunneled dual lumen CVCs rather than noncuffed, nontunneled catheters for
      temporary hemodlalysis and novel preventive technologies, such as CVCs with anti
      infective surfaces, was associated with considerably lower rates of catheter
      related BSI. CONCLUSIONS: Expressing risk of IVD-related BSI per 1000 IVD-days
      rather than BSIs per 100 IVDs allows for more meaningful estimates of risk. These
      data, based on prospective studies In which every IVD in the study cohort was
      analyzed for evidence of infection by microbiologically based criteria, show that
      all types of IVDs pose a risk of IVD-related BSI and can be used for benchmarking
      rates of infection caused by the various types of IVDs In use at the present
      time. Since almost all the national effort and progress to date to reduce the
      risk of IVD-related Infection have focused on short-term noncuffed CVCs used in
      Intensive care units, Infection control programs must now strive to consistently
      apply essential control measures and preventive technologies with all types of
      IVDs.

PMID- 16970213
TI  - Population-based prevalence of repeated group A beta-hemolytic streptococcal
      pharyngitis episodes.
AB  - OBJECTIVE: To define the population-based 3-year period prevalence of repeated
      group A beta-hemolytic streptococcal (GABHS) pharyngitis episodes in children
      between 4 and 15 years of age. PATIENTS AND METHODS: Residents of Rochester, Minn
      (age, 4-15 years), who had 3 or more GABHS pharyngitis episodes In 1 year, at
      least 1 month apart, between January 1, 1996, and December 31, 1998, were
      Identified using the resources of the Rochester Epidemiology Project (N=536).
      Pharyngitis episodes (evidence of a sore throat with or without presence of
      fever) followed by either a positive rapid streptococcus test result or a
      positive plate culture test result were considered positive GABHS episodes. Age-
      and sex-specific prevalence rates were calculated, assuming that all residents 4
      to 15 years of age in Rochester during 1996 to 1998 were at risk. RESULTS: A
      total of 208 children met our definition for repeated GABHS episodes between 1996
      and 1998 and were included in this study. Approximately 1% of children between
      the ages of 4 and 15 years experienced repeated GABHS pharyngitis episodes
      between 1996 and 1998. This estimate increased to approximately 2% among children
      4 to 6 years of age and decreased to 0.1% among children 13 to 15 years old.
      CONCLUSION: A relatively small proportion (1%) of children between 4 and 15 years
      of age experienced repeated GABHS episodes in a 3-year period; however, this
      proportion represents a substantial number of children who are affected at the
      population level. Given the increased costs associated with treating repeated
      GABHS episodes, further studies are necessary to determine how best to reduce
      episodes and treatment costs in this age group.

PMID- 16970214
TI  - Effectiveness of ezetimibe added to ongoing statin therapy in modifying lipid
      profiles and low-density lipoprotein cholesterol goal attainment in patients of
      different races and ethnicities: a substudy of the Ezetimibe add-on to statin for
      effectiveness trial.
AB  - OBJECTIVE: To examine whether the improvements in lipid profiles and low-density
      lipoprotein cholesterol (LDL-C) goal attainment found in the Ezetimibe Add-On to
      Statin for Effectiveness trial occurred equally in the black, Hispanic, and white
      patient populations enrolled in the study. PATIENTS AND METHODS: In this double
      blind, placebo-controlled study, patients were recruited from 299 community-based
      practices across the United States (January to August 2003). Patients with,
      hypercholesterolemia and LDL-C levels exceeding National Cholesterol Education
      Program Adult Treatment Panel III goals were randomized (2:1) to receive either
      ezetimibe (10 mg/d) or placebo in addition to their ongoing statin therapy for 6
      weeks. RESULTS: A total of 5802 patients were screened at baseline for the
      Ezetimibe Add-On to Statin for Effectiveness study. Of these, 2772 were excluded,
      and the remaining 3030 eligible patients were randomized. Ezetimibe, compared
      with placebo, added to statin therapy significantly reduced LDL-C levels from
      statin-treated baseline by 23.0% (white patients), 23.0% (black patients), and
      21.0% (Hispanic patients). This effect was consistent across race and ethnicity
      groups (P > .50 for treatment-by-race interactions). Ezetimibe added to statin
      therapy also statistically significantly (P < .001) increased the percentage of
      patients attaining their LDL-C goal for their National Cholesterol Education
      Program Adult Treatment Panel III risk category in black (63.0%), Hispanic
      (64.8%), and white (72.3%) patients compared with placebo plus statin (32.9%
      black patients, 19.0% Hispanic patients, and 19.7% white patients). Ezetimibe
      treatment improved other lipid parameters across groups, including triglyceride,
      high-density lipoprotein cholesterol, non-high-density ilpoprotein cholesterol,
      and total cholesterol levels. Finally, the addition of ezetimibe reduced high
      sensitivity C-reactive protein levels overall, and no significant interaction of
      treatment by race occurred (P = .83), Indicating a consistent effect across
      races. Ezetimibe was generally well tolerated, and no detectable differences
      occurred in the adverse event profile by race or ethnicity. CONCLUSION: Ezetimibe
      added to statin therapy is effective and well tolerated for improving the lipid
      profile and LDL-C goal attainment of patients regardless of race or ethnicity.

PMID- 16970215
TI  - Darbepoetin alfa administration to achieve and maintain target hemoglobin levels
      for 1 year in patients with chronic kidney disease.
AB  - OBJECTIVE: To assess the efficacy and safety of every-other-week darbepoetin alfa
      therapy in treating anemia and maintaining hemoglobin levels for 1 year in
      patients with chronic kidney disease (CKD) who were not undergoing dialysis and
      who had not previously received erythropolesis-stimulating proteins (ESPs).
      PATIENTS AND METHODS: This multicenter 52-week study (evaluation period, weeks 20
      32), a subanalysis of the Simplify the Treatment of Anemia with Aranesp study,
      enrolled patients with CKD who were not receiving dialysis (creatinine clearance
      < or =70 mL/min or estimated glomerular filtration rate [GFR] < or =60 mL/min).
      Patients evaluated in this analysis were not receiving ESPs, had hemoglobin
      concentrations less than 11 g/dL, and had transferrin saturation of 20% or higher
      during screening. Patients Initiated every-other-week darbepoetin alfa therapy at
      0.75 microg/kg, with the dose subsequently titrated to maintain hemoglobin levels
      not to exceed 12 g/dL. The first study participant was enrolled on February 4,
      2002, and the last participant completed the study on March 31, 2004. RESULTS:
      The analysis included 911 patients (mean [SD] age, 66.4 [14.2] years; 54.3%
      female; 55.3% white). The least squares mean evaluation hemoglobin concentration
      was 11.54 g/dL (95% confidence interval, 11.47-11.61 g/dL), and the change from
      baseline was 1.6 g/dL (95% confidence interval, 1.5-1.7 g/dL). The mean (SD)
      every-other-week darbepoetin alfa dose during evaluation was 44.5 (33.7) microg.
      Iron supplementation was administered to 573 patients (62.9%) during the study.
      Darbepoetin alfa was well tolerated throughout the study period. CONCLUSION:
      Darbepoetin alfa initiated every other week safely and effectively treated anemia
      and maintained hemoglobin for 1 year in patients with CKD who were not undergoing
      dialysis and who were not receiving prior ESP therapy.

PMID- 16970216
TI  - Mediastinal lymphangioma: Mayo Clinic experience of 25 cases.
AB  - OBJECTIVE: To describe the clinical findings, treatment outcomes, disease
      recurrence rates, and survival of patients with pathologically confirmed
      mediastinal and cervicomediastinal lymphangioma. PATIENTS AND METHODS: There are
      2 patient cohorts. Cohort A consisted of 12 Mayo Clinic patients with
      pathologically confirmed medilastinal or cervicomediastinal lymphangioma
      identified from 1986 to 1999. Cohort B consisted of 13 additional patients with
      mediastinal lymphangioma who had been previously reported from the Mayo Clinic
      (from 1976 to 1986). All patients were retrospectively identified, and follow-up
      was performed by either telephone or medical record review. RESULTS: The mean age
      at the time of diagnosis was 36.5 years, with a male-female ratio of 1:3. All but
      3 patients were symptomatic at presentation, with dyspnea being the most common
      symptom. Computed tomographic scans commonly revealed a homogeneous, low
      attenuation mass that often Involved vascular or airway structures. Although 3
      patients were initially observed, all patients had surgical intervention because
      of symptoms or enlargement of the mass. Thoracotomy with resection was the most
      common surgical intervention. Five recurrences were noted. Recurrence was
      minimized by complete excision of the lymphangioma. On follow-up that spanned 23
      years, 75% of patients were alive. These survival rates were not statistically
      different from the expected survival rates of the same age- and sex-matched
      controls. Only 1 death was attributed to complication from lymphangioma.
      CONCLUSION: Mediastinal and cervicomediastinal lymphangioma are rare lesions that
      can be treated successfully with surgical excision. Prognosis appears to be
      excellent because no difference in survival was found between patients and age-
      and sex-matched controls.

PMID- 16970218
TI  - A practical physicians' guide to the Medicare drug benefit plan.
AB  - Recent commentaries on Medicare Part D highlight both the early failings and the
      successes of the program. However, regardless of one's opinions about the
      program, Part D is a reality that millions of Medicare beneficiaries must address
      now and in the future. The ultimate economic, policy, and clinical success of the
      Medicare drug benefit plan depends on its transparency and ability to be
      navigated together by patients, physicians, and other parties. Although Medicare
      Part D is likely to evolve considerably in the future, it will continue to
      present elderly adults with numerous plan options and rules and therefore present
      persistent challenges for patients and physicians. By focusing on a few crucial
      aspects of Part D and taking advantage of available resources, physicians can
      simplify Part D for their patients, help them make informed decisions about
      enrollment and plan selection, and possibly help them save money with their
      current PDP. This may, in turn, reduce beneficiaries' out-of-pocket prescription
      costs, thereby improving patients' access to medications and possibly their
      medication adherence and health outcomes as well.

PMID- 16970217
TI  - Glutamic acid decarboxylase autoimmunity with brainstem, extrapyramidal, and
      spinal cord dysfunction.
AB  - OBJECTIVE: To describe novel neurological manifestations associated with glutamic
      acid decarboxylase (GAD65) autoimmunity. PATIENTS AND METHODS: This retrospective
      study (1987-2003) describes 62 patients Incidentally found to have a serum
      autoantibody that bound selectively to synapse-rich central nervous system
      tissues. The immunostaining pattern was determined to be GAD65-specific by
      radiolmmunoprecipitation assay. These cases were identified among samples
      submitted for paraneoplastic autoantibody evaluation using indirect
      immunofluorescence. In no case had GAD65 or any other islet cell antibody testing
      been requested. RESULTS: In most cases, the patients' presentations were
      initially considered neurodegenerative or inflammatory (multiple sclerosis or
      paraneoplastic). Median age at onset was 50 years, and 77% were women. Of the 44
      patients seen at the Mayo Clinic, 23% were African American; in contrast, less
      than 10% of Mayo Clinic's neurology patients are African American. Median follow
      up was 24 months. The radioimmunoprecipitation assay values for GAD65 antibody
      were extremely high (median, 1429 nmol/L; Interquartile range, 643-3078 nmol/L)
      and correlated significantly with immunofluorescence titers (median, 3840;
      interquartile range, 1920-15,360; r = 0.81; P < .001). Neurological
      manifestations were multifocal in 41 patients and included cerebellar ataxia
      (63%), brainstem involvement (29%), seizures (27%), stiff-man phenomena (26%),
      extrapyramidal signs (16%), and myelopathy (8%). One third of the patients had
      type 1 diabetes mellitus, 53% had thyroid autoantibodies, and 16% had vitiligo.
      Eleven of 20 patients identified as African American had brainstem involvement.
      Some patients appeared to benefit from short-term immunosuppression (none
      received long-term therapy). CONCLUSIONS: The neurological spectrum of GAD65
      autoimmunity includes brainstem, extrapyramidal, and spinal cord syndromes. In
      our experience, African American patients were disproportionately affected. A
      patient with a presumed neurodegenerative disorder of new onset, with high levels
      of GAD65 antibody (>20 nmol/L), merits consideration of immunotherapy.

PMID- 16970219
TI  - The safety of aggressive statin therapy: how much can low-density lipoprotein
      cholesterol be lowered?
AB  - Recent clinical trials have consistently demonstrated that reducing low-density
      lipoprotein cholesterol to very low levels will substantially reduce
      cardiovascular morbidity and mortality. The lipid-lowering agents of choice are
      the statins, which are generally considered safe and effective. Of the various
      agents available, atorvastatin and rosuvastatin are the most powerful, followed
      by simvastatin. Serious adverse effects with statin therapy are uncommon and
      primarily involve effects on the liver and skeletal muscle. The risk increases
      with the statin dose and coadministration with other drugs metabolized by the
      same metabolic pathway, such as the cytochrome P-450 system. For patients who do
      not achieve adequate reduction in low-density lipoprotein cholesterol levels with
      statin therapy of moderate potency, the clinician can up-titrate the dose of the
      initial statin, institute combination therapy and carefully monitor for adverse
      effects, or switch to a lower dose of a more potent statin. The strategy chosen
      depends on the degree of lipid lowering required and on safety, cost, and
      compliance issues. This article reviews evidence concerning the benefits of
      reducing low-density lipoprotein cholesterol levels below currently established
      targets and addresses the question of whether Intensive statin therapy is likely
      to Increase the risk of adverse events or concomitant comorbidity.

PMID- 16970220
TI  - Hypoxic liver injury.
AB  - Hypoxic liver injury is defined as a massive, but transient, increase in serum
      transaminase levels due to an imbalance between hepatic oxygen supply and demand
      in the absence of other acute causes of liver damage. It typically occurs in
      elderly individuals with right-sided congestive heart failure and low cardiac
      output. Precipitating factors include arrhythmias or pulmonary edema. Symptoms
      include weakness, shortness of breath, and right upper quadrant pain. Less
      commonly, hypoxic liver injury is seen in patients with severe hypoxemia or
      septic shock. Characteristically, the transaminase level is elevated 20-fold but
      normalizes rapidly over several days. Imaging studies reveal hypoechoic or
      hypodense lesions that resolve completely with reversal of the initiating event.
      Treatment and prognosis depend on the underlyIng disease.

PMID- 16970221
TI  - 58-year-old man with fever and right eye pain.

PMID- 16970222
TI  - Biology of platelet-derived growth factor and its involvement in disease.
AB  - Platelet-derived growth factor (PDGF) is mainly believed to be an important
      mitogen for connective tissue, especially for fibroblasts that serve in wound
      healing. However, PDGF also has important roles during embryonal development, and
      its overexpression has been linked to different types of fibrotic disorders and
      malignancies. Platelet-derived growth factor is synthesized by many different
      cell types, and its expression is broad. Its synthesis is in response to external
      stimuli, such as exposure to low oxygen tension, thrombin, or stimulation by
      other cytokines and growth factors. In addition, PDGF may function in autocrine
      stimulation of tumor cells, regulation of interstitial fluid pressure, and
      angiogenesis. Recently, several drugs were developed that are potent inhibitors
      of the tyrosine kinase activity of PDGF receptors. Thus, it is important to
      understand the physiology of PDGF and its receptors and the role of PDGF in
      different diseases. This review summarizes the physiologic activity of PDGF, the
      expression of PDGF during embryonal development, and the roles of PDGF expression
      in nonmalignant disease and in different tumors.

PMID- 16970223
TI  - An opportunity for parity: health care reform vis-a-vis behavioral health and
      substance abuse treatment.

PMID- 16970224
TI  - A morphealike skin condition caused by Borrelia burgdorferi in an
      immunocompromised patient.

PMID- 16970225
TI  - Efficacy of acupuncture vs. placebo.

PMID- 16970226
TI  - Summer shunt surgery.

PMID- 16970227
TI  - Shunt insertion in the summer: is it safe?
AB  - OBJECT: The potential for increased complications related to the arrival of new
      residents in July each year has not previously been demonstrated in the
      neurosurgical literature. The authors investigated this phenomenon in children
      undergoing cerebrospinal fluid shunt surgery. METHODS: Data were obtained from a
      multicenter hydrocephalus clinical trials database and from hospital admission
      records in English-speaking Canada. Data pertaining to patients treated in July
      and August were compared with those pertaining to patients treated during the
      remainder of the year. The incidence of shunt failure, shunt infection,
      neurological deficits, wound infection, technical errors, and death were compared
      using a chi-square test for categorical outcomes, means for continuous outcomes,
      and survival analysis for time-dependent outcomes. In the hydrocephalus clinical
      trials database, 138 of 737 patients were treated in July and August. The median
      duration of shunt lifespan (hereafter referred to as "shunt survival") was 1.7
      years for patients treated during the summer months and 2.4 years for those
      treated throughout the rest of the year (p = 0.10); for shunt infection the
      figures were 13.8 and 8.8% (p = 0.08) of the total number of cases, and for wound
      dehiscence they were 2.9 and 0.7% (p = 0.05), respectively. When all shunt
      procedures were included, an examination of shunt survival and infection
      incidence rates recorded in the Canadian Hospital Discharge Database seemed to
      imply a significant advantage to having surgery between September and June (log
      rank statistic = 7.10, p = 0.008). CONCLUSIONS: The data suggest a "July effect"
      on some outcomes related to shunt surgery, but the effect was small. Nonetheless,
      the potential morbidity of shunt failure, infection, and the cost of treatment
      indicate that continued vigilance and appropriate supervision of new staff by
      attending surgeons is warranted.

PMID- 16970228
TI  - Is there a "July phenomenon" in pediatric neurosurgery at teaching hospitals?
AB  - OBJECT: Concern for patient safety, among other reasons, recently prompted
      sweeping changes in resident work policies in the US. Some have speculated that
      the arrival of new interns and residents at teaching hospitals each July might
      cause an annual transient increase in poor patient outcomes and inefficient care.
      METHODS: Data were analyzed for 4323 craniotomies for tumor resection and 22,072
      shunt operations performed in pediatric patients between 1988 and 2000 in US
      nonfederal hospitals (Nationwide Inpatient Sample, Healthcare Cost and
      Utilization Project, Agency for Healthcare Research and Quality, Rockville, MD).
      In-hospital mortality rates, discharge outcome, complications, and efficiency
      measures (length of stay [LOS] and hospital charges) for patients treated in July
      and August were compared with similar data for patients in other months. There
      were no significant increases in any adverse end point for either tumor or shunt
      operations in July and August. Odds ratios (95% confidence interval [CI]) for
      outcome of tumor craniotomies performed in July and August compared with outcome
      for tumor craniotomies performed in other months were as follows: for mortality
      rate, 0.43 (0.14-1.32); for adverse discharge disposition, 1.03 (0.71-1.51); for
      neurological complications, 1.00 (0.63-1.59); for transfusion, 0.70 (0.41-1.19).
      Hospital charges were 0.5% lower (range -6 to 5%) in July and August, and LOS was
      3% shorter (range -8 to 3%). Odds ratios (95% CI) for July or August shunt
      surgery compared with shunt surgery performed in other months were as follows:
      for mortality rate, 0.96 (0.58-1.60); for adverse discharge disposition, 0.85
      (0.66-1.11); for neurological complications, 1.27 (0.75-2.16); for transfusion,
      0.81 (0.48-1.37). Hospital charges were 0.2% higher in July and August (range -3
      to 3%), and LOS was 3% shorter (range -5 to 0.5%). CONCLUSIONS: Although moderate
      increases in some adverse end points could not be excluded, there was no evidence
      that brain tumor or shunt surgery performed in pediatric patients at US teaching
      hospitals during July and August is associated with more frequent adverse patient
      outcome or inefficient care than similar surgery performed during other months.

PMID- 16970229
TI  - Management of shunt infections: a multicenter pilot study.
AB  - OBJECT: Approximately 10% of cerebrospinal fluid (CSF) shunt operations are
      associated with infection and require removal or externalization of the shunt, in
      hospital treatment with antibiotic agents, and insertion of a new shunt. In a
      previous survey, the authors identified substantial variation in the duration of
      antibiotic therapy as well as the duration of hospital stay. The present
      multicenter pilot study was undertaken to evaluate current strategies in the
      treatment of shunt infection. METHODS: Patients were enrolled in the study if
      they had a successful treatment of a CSF shunt infection proved by culture of a
      CSF specimen. Details of their care and the incidence of culture-proved
      reinfection were recorded. Seventy patients from 10 centers were followed up for
      1 year after their CSF shunt infection. The initial management of the infection
      was shunt externalization in 17 patients, shunt removal and external ventricular
      drain insertion in 50, and antibiotic treatment alone in three. Reinfection
      occurred in 18 patients (26%). Twelve of the 18 reinfections were caused by the
      same organism and six were due to new organisms. The treatment time varied from 4
      to 47 days, with a mean of 17.4 days for those who later experienced a
      reinfection compared with 16.2 days for those who did not. The most common
      organism (Staphylococcus epidermidis, 34 patients) was associated with a
      reinfection rate of 29% and a mean treatment time of 12.8 days for those who
      suffered reinfection and 12.5 days for those who did not. CONCLUSIONS:
      Reinfection after treatment of a CSF shunt infection is alarmingly common.
      According to the data available, the incidence of reinfection does not appear to
      be related to the duration of antibiotic therapy.

PMID- 16970230
TI  - Injury outcomes in children following automobile, motorcycle, and all-terrain
      vehicle accidents: an institutional review.
AB  - OBJECT: The authors performed an analysis of retrospectively obtained data to
      compare the outcomes of pediatric patients admitted to their institution for
      traumatic injuries resulting from car, motorcycle, and all-terrain vehicle (ATV)
      accidents. METHODS: The authors conducted a retrospective review of Columbus
      Children's Hospital's Trauma Registry data collected between January 1993 and
      December 2003. Data obtained in patients admitted with motor vehicle-related
      injuries were compiled for a total of 1608 patient records. Data regarding sex,
      age, hospital length of stay (LOS), Glasgow Coma Scale (GCS) score, revised
      trauma score, injury severity score (ISS), and use of a protective device were
      analyzed. CONCLUSIONS: Of 1608 patients, 1257 (78%) were injured in automobile
      accidents, 123 (7.6%) in motorcycle accidents, and 228 (14.2%) in ATV accidents.
      Injuries sustained in all vehicle types peaked during the summer months. Patients
      involved in automobile crashes presented with significantly lower GCS scores than
      those injured in motorcycle and ATV accidents; however, there was no
      statistically significant difference in LOS among all three injury modalities.
      Protective devices were underutilized in all three motor vehicle categories but,
      when used, were associated with significantly higher GCS scores, ISSs, and
      shorter LOSs among patients admitted after automobile accidents. The correlation
      of seat belt use with better outcomes underscores the necessity to improve motor
      vehicle safety education for children, who are less likely to be restrained as
      they age.

PMID- 16970231
TI  - Complications and pitfalls of neuroendoscopic surgery in children.
AB  - OBJECT: Neuroendoscopic surgery is being used as an alternative to traditional
      shunt surgery and craniotomy in the management of hydrocephalus and intracranial
      fluid-filled cavities. In this study, the authors evaluated the incidence and
      type of complications occurring after neuroendoscopic procedures that were
      performed in a consecutive series of pediatric patients at a single institution
      to determine the effectiveness of neuroendoscopy in such patients. METHODS: Four
      hundred ninety-five neuroendoscopic procedures were consecutively performed in
      450 pediatric patients at one institution over a 10-year period. Charts were
      retrospectively reviewed. A complication was defined as follows: 1) any
      postoperative neurological deficit that was not observed before surgery; 2) any
      event occurring during surgery that resulted in the procedure being aborted; or
      3) any adverse event occurring within 7 days postsurgery that resulted in a
      modification of the normal postoperative care. However, headache, vomiting, and
      fever without cerebrospinal fluid (CSF) pleocytosis were not considered
      complications. Complications were observed in 40 (8.1%) of 495 procedures. Two
      patients had two complications. One patient died of diffuse brain edema following
      endoscopic biopsy sampling of a basal ganglia tumor (mortality rate 0.2%). Other
      complications observed were abandonment of the procedure in eight cases, CSF
      leakage in 11 (with associated wound infection in one), intraventricular
      hemorrhage in six (with external drainage needed in four), intraparenchymal
      hemorrhage in three, subdural collection in eight (with subdural-peritoneal shunt
      placement needed in seven), transient oculomotor palsy in two, and transient
      hemiparesis in one. CONCLUSIONS: Many complications can be avoided by determining
      the correct diagnosis and using suitable techniques and instruments. Most
      complications can be managed conservatively and do not produce long-term
      morbidity. Complex procedures in most patients and simple procedures in patients
      with preoperative risk factors carry the highest hazard. Every attempt should be
      made to optimize the surgical technique. The most serious and potentially the
      most lethal complication remains arterial bleeding from injury to the basilar
      artery complex.

PMID- 16970232
TI  - Neuroendoscopic management of interhemispheric cysts in children.
AB  - OBJECT: Interhemispheric arachnoid cysts are very rare, and they are often
      associated with complex brain malformations such as corpus callosum agenesis and
      hydrocephalus. Debate remains concerning the proper management of these lesions.
      Placement of shunts and microsurgical marsupialization of the cyst are the
      traditional options. Using endoscopic methods to create areas of communication
      between the cyst, the ventricular system, and/or the subarachnoid space is an
      attractive alternative to the use of shunts and microsurgery. METHODS: Between
      2000 and 2005, seven consecutive pediatric patients with interhemispheric
      arachnoid cysts underwent neuroendoscopic treatment involving
      cystoventriculostomy in two patients, cystocisternostomy in two, and
      cystoventriculocisternostomy in three. There were three cases of associated
      hydrocephalus, six cases of corpus callosum agenesis, and one case of corpus
      callosum hypogenesis. The follow-up period ranged from 12 to 49 months (mean 31.6
      months). Endoscopic procedures were completely successful in all but two
      patients. In one of the remaining two patients, a repeated endoscopic
      cystocisternostomy was performed with success because of closure of the previous
      stoma. In the other, a subcutaneous collection of cerebrospinal fluid (CSF) was
      managed by insertion of an lumboperitoneal shunt. A subdural collection of CSF
      developed in three patients; it was treated with insertion of a subduroperitoneal
      shunt in one patient and managed conservatively in the other two patients,
      resolving spontaneously without further treatment. Neurodevelopmental evaluation
      performed in six patients showed normal intelligence (total intelligence quotient
      [IQ] > 80) in three patients, mild developmental delay (total IQ 50-80) in two,
      and severe developmental delay (total IQ < 50) in one. CONCLUSIONS: Endoscopic
      treatment of interhemispheric cysts can be considered a useful alternative to
      traditional treatments, even if some complications are to be expected, such as
      subdural or subcutaneous CSF collections and CSF leaks due to thinness of
      cerebral mantle and to the often-associated multifactorial hydrocephalus.

PMID- 16970233
TI  - Impact of prenatal magnetic resonance imaging on postnatal neurosurgical
      treatment.
AB  - OBJECT: The goal of this study was to determine the importance magnetic resonance
      (MR) imaging holds as a complementary fetal imaging modality to ultrasonography
      in deciding postnatal neurosurgical management. METHODS: Between 1999 and 2003,
      320 fetal MR imaging studies were performed at a single institution. Twenty-four
      fetuses were found to have central nervous system abnormalities that could
      potentially require a neurosurgical intervention. The diagnoses included spinal
      anomalies (scoliosis, myelomeningocele, and closed spinal dysraphism) and brain
      anomalies (ventriculomegaly with or without hemorrhage, intracranial cyst,
      craniosynostosis, and encephalocele). Fourteen of the 24 fetuses underwent
      surgery based on findings of prenatal MR imaging. In seven cases the pregnancy
      was terminated, and in three cases conservative follow up continues. CONCLUSIONS:
      In a variety of brain and spine disorders, prenatal MR imaging can delineate and
      characterize the abnormality, and thus assist in the diagnosis and in the
      planning of postnatal surgery and management. This modality provides important
      multiplanar images and may obviate the need for early postnatal computed
      tomography or MR imaging. Postnatal management can often be guided by prenatal MR
      imaging findings.

PMID- 16970234
TI  - Significance of preserving the vein of Labbe in epilepsy surgery involving
      temporal lobe resection.
AB  - OBJECT: Preservation of the vein of Labbe is recommended to prevent temporal lobe
      infarction after skull base surgery. However, the importance of preserving the
      vein in epilepsy surgery involving resection of the temporal lobe is unclear.
      METHODS: Retrospective analysis was performed in 47 cases, in which patients
      underwent temporal lobe resection, out of 148 cases in which patients underwent
      surgery for intractable seizures over a 5-year period. Standard temporal lobe
      resection anterior to the vein of Labbe was performed in 11 patients. In 24
      patients, the temporal lobe resection extended posterior to the vein of Labbe;
      the vein was preserved in eight patients, who underwent surgery prior to 2002,
      and resected in the other 16 patients, who underwent surgery after 2002. Twelve
      patients underwent a temporoparietooccipital resection. There was no significant
      difference in the pattern of venous anatomy (based on analysis of the relative
      size of veins [chi-square test, p = 0.1] and the number of superficial veins
      draining the temporal lobe [p = 1]) in patients in whom the vein was resected
      compared with those in whom it was preserved. No patient experienced
      postoperative infarction. CONCLUSIONS: The authors conclude that the vein of
      Labbe may be safely resected in epilepsy surgery involving temporal lobe
      resection. The decision whether to resect the vein need not be based on the
      surface venous drainage pattern or number of veins draining the temporal lobe.

PMID- 16970235
TI  - Minimal tethered cord syndrome associated with thickening of the terminal filum.
AB  - OBJECT: The authors investigated the occurrence of anatomical abnormalities of
      the terminal filum in children undergoing surgical filum lysis for minimal
      tethered cord syndrome (TCS). METHODS: Five consecutive children (age range 6-12
      years) with medically refractory voiding dysfunction but no magnetic resonance
      (MR) imaging-documented lumbosacral abnormality on 1.5-tesla sequences underwent
      preoperative urodynamic studies consisting of calibrated uroflowmetry,
      cystometrography, and voiding cystourethrography. Urodynamic bladder function was
      abnormal in each case. A sixth child (5 years of age) who had progressive lower
      extremity weakness, gait abnormality, and voiding dysfunction, but in whom there
      was no MR imaging-documented lumbosacral abnormality, was also included. These
      six children experienced improved bladder function after terminal filum lysis.
      Histologically, the terminal filum in these patients was fattier, thicker, and
      more densely fibrous than that in three reference patients undergoing incidental
      terminal filum lysis during selective dorsal rhizotomy or resection of a lumbar
      dermal sinus tract. All four patients with voiding dysfunction who underwent
      postoperative urodynamic testing experienced corresponding improvement in bladder
      function. CONCLUSIONS: Significant improvement of voiding dysfunction after
      surgical lysis of the terminal filum in children with MR imaging-documented
      normal lumbosacral spines was observed. In such children, in whom neurogenic
      dysfunction is identified by urodynamic testing, structural abnormalities of the
      terminal filum may exist. A prospective randomized controlled study of children
      undergoing surgical terminal filum lysis in cases of minimal TCS should be
      undertaken.

PMID- 16970236
TI  - Outcomes in patients undergoing single-trajectory endoscopic third
      ventriculostomy and endoscopic biopsy for midline tumors presenting with
      obstructive hydrocephalus.
AB  - OBJECT: The primary aim of this study was to evaluate the success of endoscopic
      third ventriculostomy (ETV) as a treatment for obstructive hydrocephalus
      secondary to midline tumors (midbrain, pontine, pineal, tectal plate, thalamic,
      and third ventricular regions). In addition, the study examined the role and
      value of endoscopic tumor biopsy (ETB) in the management of such cases. All
      surgical procedures were performed through a single-trajectory approach. METHODS:
      A retrospective analysis of clinical notes, operation records, and pre- and
      postventriculostomy neuroimaging data was performed to determine the success or
      failure and complications of ETV and ETB in 42 patients presenting with tumor
      induced obstructive hydrocephalus. Patient data were derived from an endoscopy
      database initiated in 1998. The study population included 21 female and 21 male
      patients (mean age 37 years, range 5-77 years). All 42 patients underwent an ETV;
      33 of the 42 underwent an ETV and an ETB (single-trajectory). One patient was
      excluded from the follow-up analysis due to rapid deterioration of his condition
      from tumor progression. The duration of follow up ranged from 3 to 84 months
      (mean 32 months). At the last follow up, 11 patients with ETVs had undergone
      shunt placement and two patients had undergone repeated ETVs, giving a long-term
      success rate of 68% (28 of 41 cases) for single ETV as a treatment for
      hydrocephalus at presentation. Statistical analysis revealed no significant
      relationship (p > 0.92) between tumor location and ETV success or failure. The
      mean time to ETV failure was 32 weeks. Histological examination of biopsy
      specimens was non-diagnostic in eight (24%) of the 33 cases in which ETB was
      performed. Seven of these cases involved pineal region tumors and one involved a
      tectal plate tumor. There was no death or major morbidity associated with ETV and
      ETB in this series. CONCLUSIONS: Endoscopic third ventriculostomy is a safe and
      durable means of controlling hydrocephalus in tumor cases. Its success rate is
      high--comparable to that reported in aqueduct stenosis cases. Although ETB is
      probably not as accurate for diagnosis as biopsy with frame-based stereotactic
      guidance, it is associated with a lower mortality rate and, in the correct
      clinical setting, may be justifiably attempted as an initial biopsy procedure at
      the same time as ETV via a single-trajectory approach.

PMID- 16970237
TI  - Constipation as a reversible cause of ventriculoperitoneal shunt failure. Report
      of two cases.
AB  - Ventriculoperitoneal (VP) shunt failure is a common problem encountered by
      pediatric neurosurgeons. The majority of such failures are due to obstruction of
      the device. Conditions in which intraabdominal pressure is chronically elevated,
      such as pregnancy, have been associated with shunt failure. Chronic constipation
      may also result in abnormally elevated intraabdominal pressure and may be an
      underrecognized cause of distal VP shunt failure. The authors describe the cases
      of two children who presented with clinical and imaging evidence of VP shunt
      failure and who were also severely constipated. Treatment of their constipation
      resulted in both clinical and imaging-documented resolution of their shunt
      failure.

PMID- 16970238
TI  - Ventriculoperitoneal shunt occlusion due to spontaneous intraabdominal knot
      formation in the catheter. Case report.
AB  - A male infant was born full term with a prenatally diagnosed lumbosacral
      meningomyelocele and dilated ventricles that required ventriculoperitoneal shunt
      treatment. Following shunt insertion, a dysfunction occurred and operative
      exploration of the distal catheter revealed a knot formation resulting in
      occlusion of the shunt lumen. After the knot was untangled, the symptoms of
      increased intracranial pressure diminished. The authors stress that any possible
      cause of mechanical shunt complication should be taken into account when shunt
      malfunction is expected.

PMID- 16970239
TI  - Delayed lead pulmonary emboli after a gunshot wound to the head. Case report.
AB  - Bullet fragment emboli are uncommon, and there have been only a few reports of
      intracranial-to-extracranial migration of these fragments. The authors present
      the case of an 11-year-old girl who was struck in the suboccipital region with a
      "soft nose" bullet fired at close range. Several months later, the patient was
      found to have asymptomatic pulmonary emboli. Similar cases are reviewed, and a
      management strategy is recommended.

PMID- 16970240
TI  - Epidural-cutaneous fistula in association with the Pott puffy tumor in an
      adolescent. Case report.
AB  - The Pott puffy tumor is a subperiosteal abscess associated with underlying
      osteomyelitis, most often of the frontal bone in conjunction with frontal
      sinusitis. Intracranial sequelae can include epidural abscess, subdural empyema,
      intraparenchymal abscess, meningitis, and dural venous thrombophlebitis, all with
      resultant neurological deterioration. Although once common, this entity has
      become rare since the introduction of antibiotic agents. The authors present an
      unusual case of a 14-year-old girl suffering from the Pott puffy tumor whose
      condition was further complicated by a draining epidural-cutaneous fistula and an
      epidural abscess.

PMID- 16970241
TI  - Dysplasia of C-1 and craniocervical instability in patients with Shprintzen
      Goldberg syndrome. Case report and review of the literature.
AB  - Shprintzen-Goldberg syndrome is a rare connective tissue disorder characterized
      by marfanoid habitus and additional dysmorphic stigmata. Craniocervical anomalies
      occur in fewer than 30% of cases. Serious vertebral instability can also occur,
      albeit rarely. The authors report on the first patient treated with surgical
      fusion at the craniocervical junction because of a C-1 dysplasia and severe
      instability. The skeletal and cardiovascular anomalies that can pose additional
      problems for surgical treatment and perioperative care are discussed in detail.

PMID- 16970242
TI  - HSP70 expression in the hippocampal CA3 subfield in different chronic stress
      models.
AB  - This study examined the heat shock protein 70 (HSP70) expression in hippocampal
      CA3 subfield of rats in different chronic stress models. The chronic restraint
      stress (CRS) and the chronic mild stress (CMS) models were used in this study.
      Observation of exploratory behavior in an open field test indicated stress level.
      The expression of HSP70 in hippocampal CA3 subfield was measured by
      immunohistochemical methods. The results showed that the number of quadrant
      crossing in both CRS and CMS groups decreased more than that of the control (P <
      0.01). CRS group crossing decreased more than CMS group. Damage in the
      hippocampus of the CMS group occurred later and to a less extent than that of the
      CRS group. Compared with CMS group, the expression of HSP70 was greater in the
      CRS group. Moreover, increased stress duration enhanced these effects. These
      results show that the CRS model affects both exploratory behavior and HSP70
      expression in the hippocampus more dramatically than the CMS model.

PMID- 16970243
TI  - Pharmacological and biophysical properties of swelling-activated chloride channel
      in mouse cardiac myocytes.
AB  - The present study was designed to observe the properties of swelling-activated
      chloride channel (ICl.swell) in mouse cardiac myocytes using patch clamp
      techniques. In whole-cell recordings, hypotonic solution activated a chloride
      current that exhibited outward rectification, weak voltage-dependent
      inactivation, and anion selectivity with permeability sequence of I- > Br- > Cl-.
      The current was sensitive to Cl- channel blockers tamoxifen, NPPB and DIDS. In
      single-channel recordings, cell swelling activated a single channel current which
      showed outward rectification with open probability of 0.76 +/- 0.08 and
      conductance of 38.1 +/- 2.5 pS at +100 mV under [Cl-] symmetrical condition. I-V
      relation revealed the reversal potential as expected for a Cl(-)-selective
      channel. These results suggested that in mouse cardiac myocytes, swelling
      activated, outward rectifying chloride channel with a single channel conductance
      of 38.1 +/- 2.5 pS (at +100 mV under [Cl-] symmetrical condition) underlies the
      volume regulatory Cl- channel.

PMID- 16970244
TI  - Effects of selective estrogen receptor modulator raloxifene plus 17-beta
      estradiol in aorta and mammary gland of female experimental atherosclerosis
      rabbits and possible involvement of ERK signal transduction pathway.
AB  - The present study investigated the effects of raloxifene, a second generation
      selective estrogen receptor modulator (SERM), plus 17-betaE2 on aortic
      atherosclerosis and mammary gland hyperplasia in ovariectomized, cholesterol-fed
      rabbits. Following 10 weeks of raloxifene, 17-betaE2, or raloxifene plus 17
      betaE2 administration, serum total cholesterol, triglyceride, low density
      lipoprotein were significantly decreased in the drug groups compared to the
      placebo group. Consistent with serum lipid results, the total lesion area for
      each aorta of the drug groups decreased significantly as compared to the placebo
      group. HE staining of aorta paraffin section showed that in the drug groups the
      endothelial monolayer was almost continuous. While in mammary gland, HE staining
      of paraffin sections indicated the hyperplasia of epithelial cells (in 17-betaE2
      group) was obviously inhibited in raloxifene plus 17-betaE2 group. In cultured
      vascular smooth muscle cell (VSMC), the results of MTT and [3H]TdR incorporation
      showed that the drug groups could inhibit AngII-induced proliferation of VSMC.
      Western blotting proved that raloxifene plus 17-betaE2 inhibited the expression
      of phosphorylated ERK protein, similar to 17-betaE2 but different from
      raloxifene. This effect was inhibited by PD98059 (inhibitor of MAPK) or ICI182780
      (ER antagonist). In conclusion, this study suggests that SERM raloxifene plus 17
      betaE2 improves the lipid metabolism and relieves the aorta changes of female
      experimental atherosclerosis rabbits, which are partly implemented by the
      inhibition of VSMC growth through ERK cascade. The hyperplasia of mammary gland
      epithelial cells could be significantly inhibited by raloxifene plus 17-betaE2.

PMID- 16970245
TI  - Paraquat-induced lipid peroxidation: effects of ovariectomy and estrogen receptor
      antagonist.
AB  - Estrogen protects females against cardiovascular diseases in both receptor
      dependent, genomic or non-genomic manner. Although part of the protective effects
      is attributed to its enhancement of nitric oxide (NO) production and antioxidant
      properties, in vivo evidence is difficult to establish. We thus employed paraquat
      (PQ)-treated rats as a model for oxidative stress and to compare oxidative damage
      determined by malondialdehyde (MDA) contents as index for lipid peroxidation of
      various tissues. Samples from aorta, lung, and liver exhibited low but detectable
      MDA level in intact control rats; sham operation did not but PQ-treatment
      significantly enhanced the MDA levels of all tissues. Different hormonal status
      were achieved by comparing sham-operated (sham), sham treated with estrogen
      receptor antagonist ICI182,780 (ICI), and ovariectomized (OVX) rats. OVX
      significantly reduced plasma estrogen level, ICI effectively blocked estrous
      cycle without reducing estrogen level. Derived from rats subjected to identical
      PQ treatment, MDA level was significantly higher in OVX rats than that of sham in
      isolated aortic rings. In lung tissues, MDA level were similar in all groups. In
      liver tissues, ICI rats exhibited higher level of MDA than both sham and OVX
      rats. These data indicated that hormonal status could affect the degree of lipid
      peroxidation under similar oxidative stress induced by PQ, and that not all
      tissues responded identically.

PMID- 16970246
TI  - Glucose tolerance and insulin sensitivity following an one-week volleyball
      competition.
AB  - The purpose of the study was to compare glucose tolerance and insulin sensitivity
      between trained (TR) and competition (CP) states, in relation to cortisol and
      testosterone levels. Sixteen highly trained volleyball players voluntarily
      participated in this study. The first testing session (TR state) occurred 1 week
      before the start of national level volleyball CP, and the second testing session
      (CP state) occurred next morning after the 1-week CP. Fasted serum sample was
      used for measuring cortisol and testosterone. Subjects were then orally
      challenged with 75 g of glucose solution for determinations of oral glucose
      tolerance test (OGTT) and insulin response. Under both fasted and glucose
      challenged conditions, glucose levels of CP were not different from TR state,
      whereas insulin levels of CP were significantly elevated above TR (50 min: from
      78.8 +/- 8.7 to 96.6 +/- 8.1 microU/ml, P < 0.05; 80 min: from 62.8 +/- 7.0 to
      82.0 +/- 7.3; P < 0.05). Muscle creatine kinase (CK) level in blood was
      significantly increased above TR, suggesting greater muscle damage by CP. Serum
      leptin level, percent fat mass, and body weight were not different between two
      states. CP significantly increased serum cortisol level without significantly
      change in testosterone level. The new finding of the study was that volleyball CP
      reduced the whole-body insulin sensitivity significantly compared to TR state.
      The greater level of insulin concentration under CP state appears to be
      associated with elevated serum cortisol level. Despites the benefit of increased
      physical activity on metabolic function is widely recognized, physiological
      stress associated with CP can result in attenuation of systemic insulin
      sensitivity compared TR state.

PMID- 16970247
TI  - Effect of taurine on gastric oxidative stress and hemorrhagic erosion in brain
      ischemic rats.
AB  - The effect of taurine on gastric hemorrhage and mucosal erosion in the brain
      ischemia (BI) is unknown. The aim of the research was to study the involvement of
      gastric oxidative stress in hemorrhagic erosion produced in BI rats. The
      protective effect of taurine on this erosion model was evaluated. Male Wistar
      rats were deprived of food for 24 h. Under chloral hydrate -anesthesia, bilateral
      carotid artery ligation (BCAL) was performed 12, 18 and 21 h after removal of
      food to obtain 12, 6 and 3 h of BI duration. The pylorus and carotid esophagus of
      rats also were ligated. The stomachs were then irrigated for 3 h with normal
      saline or simulated gastric juice containing 100 mM HCl plus 17.4 mM pepsin and
      54 mM NaCl. The stomach was dissected. Gastric samples were harvested. The rat
      brain was dissected for examination of ischemia by using triphenyltetrazolium
      chloride staining method. Changes in gastric ulcerogenic parameters, such as
      decreased mucosal GSH level as well as enhanced gastric acid back-diffusion,
      mucosal lipid peroxide generation, histamine concentration, luminal hemoglobin
      content and mucosal erosion in gastric samples were measured. The results
      indicated that BCAL could produce severe BI in rats. Moreover, a BI- duration
      dependent exacerbation of various ulcerogenic parameters also was observed in
      these rats. Intraperitoneal taurine (0-300 mg/kg) dose-dependently ameliorated
      gastric oxidative stress and hemorrhagic erosion in BI rats. Taken together, BI
      could produce gastric oxidative stress and hemorrhagic erosions that was
      ameliorated by taurine through stimulation of GSH biosynthesis and inhibition of
      oxidative stress.

PMID- 16970248
TI  - Changes of nitric oxide synthase-containing nerve fibers and parameters for
      oxidative stress after unilateral cavernous nerve resection or manuplation in rat
      penis.
AB  - After pelvic surgeries such as radical prostatectomy, two major complications-
      urinary incontinence and erectile dysfunction (ED) may occur. Etiologies for ED
      are multiple pathologic mediators/systems. Oxidative stress, which is known to be
      induced after surgical trauma, could be a cause of ED. The purposes of in this
      study are to investigate the effect of unilateral manipulation/ dissection and
      resection of the cavernous nerve (neurotomy) to NOS (nitric oxide synthase)
      containing nerve fibers and pressure after electro stimulation in rat corpus
      cavernosum, and to determine whether these procedures would produce oxidative
      stress within rat cavernous tissue 3 weeks and 6 months after the operation. Male
      rats were divided into 5 groups. Rats in groups 1 and 2 underwent unilateral
      cavernous nerve manipulation and sacrificed 3 weeks and 6 months after the
      operation, respectively. Rats in groups 3 and 4 underwent unilateral neurotomy of
      a 5-mm. segment of the cavernous nerve, and they were sacrificed 3 weeks and 6
      months after nerve ablation, respectively. Group 5 rats were control animals for
      biochemical analysis. Intracavernous pressure following electro stimulation
      reduced is significantly 3 weeks after unilateral resection, as compared to that
      of the manipulated nerve (P < 0.05), and it recovered 6 months after neurotomy.
      The recovery was also confirmed by NADPH (nicotinamide adenine dinucleotide
      phosphate) diaphorase staining in neurotomy groups. Lipid peroxidation, which is
      an indicater of oxidative stress, was determined by measuring thiobarbituric acid
      reacting substance (TBARS) levels and superoxide dismutase (SOD) activity. These
      markers indicated that unilateral cavernous nerve manipulation or resection
      produced oxidative stress within rat corpus cavernosum. Oxidative stress was more
      prominent 3 weeks after unilateral neurotomy (P < 0.05). Also, compared to the
      control animal group, oxidative stress was observed three weeks after
      manipulation of unilateral cavernous nerve (P < 0.05). Resection of the cavernous
      nerve caused more prominent oxidative stress than in the manipulation group. This
      study suggested, that unilateral cavernous neurotomy caused a decrease of intra
      cavernous pressure and NOS fibers in rat corpus cavernosum, and they recovered 6
      months after neurotomy. Our data also provided evidence that neurotomy and
      manipulation of the cavernous nerve caused oxidative stress in rat corpus
      cavernosum and that oxidative stress was more prominent in the nerve resection
      group.

PMID- 16970249
TI  - Renal transplantation across the ABO barrier.
AB  - Some patients with end-stage renal disease do not have suitable living related
      donors due to ABO incompatibility. Crossing the ABO barrier has long been
      considered an absolute contraindication to kidney transplantation. Although
      transplantation using A2 kidneys has been performed in a few centers over the
      past two decades with variable success, the presence of blood group antigens can
      cause immediate or early graft loss due to preformed antibody-mediated hyperacute
      rejection. Over the past few years, novel protocols designed to reduce anti-donor
      antibodies have allowed successful transplantation across the ABO barrier. This
      requires careful preoperative conditioning, which will be described in this
      article.

PMID- 16970250
TI  - The renal allograft donor with isolated microhematuria.
AB  - Recently, there has been extensive debate about extending the criteria for
      accepting living donors to include the presence of mild renal abnormalities such
      as isolated microhematuria. Hematuria defined as the detection of greater than
      five red blood cells per high power field can be associated with abnormalities
      throughout the urinary tract. Detection of casts or dysmorphic red blood cells in
      the urine sediment with or without proteinuria could indicate underlying
      intrinsic renal disease. Anatomic causes, such as stones and tumors, should be
      excluded; cystoscopy may be indicated to exclude bladder pathology. Obviously,
      urinary tract infection, uncontrolled hypertension and latent diabetes mellitus
      must be excluded. Microscopic hematuria could be associated with mesangial IgA
      deposits; as 10% of first-degree relatives of patients with IgA
      glomerulonephritis suffer from microhematuria and/or proteinuria that may require
      consideration of renal biopsy. Microhematuria could also be associated with other
      known hereditary renal diseases such as C3 deposits disease, IgM nephropathy,
      autosomal dominant polycystic kidney disease, Alport's syndrome or thin basement
      membrane disease. In conclusion, careful assessment of isolated microhematuria,
      in the context of living kidney donation, is mandatory as results may reveal
      occult renal disease that may contraindicate kidney donation.

PMID- 16970251
TI  - Autosomal dominant Alport's syndrome: study of a large Tunisian family.
AB  - Alport's syndrome is a hereditary nephritis that may lead to end-stage renal
      disease (ESRD) in early adult life. It is a clinically and genetically
      heterogeneous nephropathy. Alport's syndrome is often associated with
      sensorineural deafness and/or ocular abnormalities. In contrast with the well
      known X-linked phenotype, very little is known about the autosomal dominant form
      caused by mutations in COL4A3 and COL4A4 in the chromosome region 2q35-q37. We
      describe a Tunisian family with autosomal dominant Alport's syndrome in which
      males and females were equally affected. Two members reached ESRD at age 40 and
      53 years, respectively. Three members experienced isolated microhematuria and one
      member experienced sensorineural deafness. No eye abnormalities were observed.
      Immunohistochemical studies showed a normal distribution of the alpha5 (type IV
      collagen) chain in the epidermal basement membrane. Genetic analysis demonstrated
      that a common haplotype co-segregated with the disease in the heterozygous state
      in all affected patients, thereby, confirming an autosomal dominant mode of
      inheritance. The same haplotype was observed in two asymptomatic children. We
      conclude that autosomal dominant Alport's syndrome, follows a rare mode of
      inheritance and exhibits a milder phenotype than usually observed in classic X
      linked Alport's syndrome. The frequency of this mode of inheritance should be
      confirmed by a larger study.

PMID- 16970252
TI  - High prevalence of masked hypertension in treated hypertensive patients with type
      2 diabetes mellitus.
AB  - This study was undertaken to determine whether self-measured home blood pressure
      (BP) readings were comparable to clinic visit BP readings in hypertensive type II
      diabetic patients. We measured the BP of 27 hypertensive patients at home and
      during the clinic visits over a three week period. The BP readings were analyzed
      using a mixed linear model with mean daytime ambulatory measure as a covariate.
      We found that, although there was no significant difference in the mean systolic
      BP between home and clinic readings (0.6 mm Hg), the mean home BP readings were
      significantly higher (difference = 6.8 mm p < 0.0006). The proportion of masked
      hypertension, defined as elevated home systolic or diastolic BP (or both) values
      despite normal clinic visit BP values, was 40.7%. Three diastolic and one
      systolic BP measurement at home achieved a reliability coefficient of 0.8. Self
      measurement of BP gave highly reliable readings when they were compared with
      blind readings taken by a trained professional using a mercury sphygmomanometer.
      We conclude that self-measured BP at home identifies a high prevalence of masked
      hypertension in treated hypertensive type 2 diabetic patients and that it
      represents a valuable management adjunct to ensure maximum benefit from
      antihypertensive drug therapy.

PMID- 16970253
TI  - Tolerance and efficacy of interferon-alpha in hemodialysis patients in Tripoli.
AB  - A prospective non-randomized study was conducted at the Department of Infectious
      Diseases at Tripoli Medical Center. We evaluated the tolerance and efficacy of
      interferon-alpha (IFN) monotherapy in our hemodialysis (HD) patients with chronic
      hepatitis C virus (HCV) infection. Patients with evidence of active viral
      infection i.e. positive polymerase chain reaction (PCR) results and who were
      potential transplant candidates were included in the study. They received three
      million units of IFN-alpha, administered subcutaneously, three times a week for
      12 months. The treatment was discontinued in 12 out of the 35 treated patients
      (i.e drop out rate 34.2%). Among the 23 patients who completed the treatment
      course, 14 (60.8%) became PCR negative, and by the end of eighteen months, nine
      of the patients maintained PCR negativity (39%). Thus, a sustained virological
      response was observed in nine (25.7%) of the 35 enrolled patients. Our study
      suggests that the efficacy of IFN-alpha in our patients was less than anticipated
      and the tolerance to the drug was poor. However, studies involving larger numbers
      of patients are required to optimize the treatment protocol.

PMID- 16970254
TI  - Correlation of serum magnesium with serum parathormone levels in patients on
      regular hemodialysis.
AB  - Secondary hyperparathyroidism (SHPT) is a common, important, and treatable
      complication of end-stage renal disease. This study was conducted to investigate
      the role of serum magnesium (Mg) in regulating the secretion of parathyroid
      hormone (PTH) by the parathyroid gland in patients on maintenance hemodialysis
      (HD). Pre-dialysis serum levels of calcium (Ca), phosphorus (P), Mg, alkaline
      phosphatase (ALP), intact serum PTH (iPTH), serum 25-hydroxy Vitamin D (25-OH Vit
      D) and plasma bicarbonate (HCO3) were measured. The Urea Reduction Rate as well
      as duration and dosage of HD treatment were noted. Our study did not show any
      significant correlation between serum Mg levels and duration of HD treatment,
      levels of serum ALP, and plasma HCO3, Ca and P. An inverse correlation, albeit
      insignificant, was found between the serum Mg levels and iPTH (r = -0.30 p =
      0.079); also, a significant positive correlation was found between serum Mg
      levels and serum 25-OH Vit D levels (r = 0.40 p = 0.009). Our findings are in
      agreement with previous data, which suggest that factors other than serum Mg are
      more important in the regulation of PTH secretion in HD patients. A positive and
      strong association between serum Mg with 25-OH Vit D needs to be studied in
      greater detail.

PMID- 16970255
TI  - Epstein-Barr viral infection in renal allograft recipients: a single center
      experience.
AB  - In this study we attempted to identify the factors involved in Epstein-Barr viral
      (EBV) infection among renal allograft recipients. We studied 68 renal allograft
      recipients hospitalized at the Imam Khomeini Medical Center from 2001 to 2004.
      Blood samples were obtained from the patients before renal transplantation and
      repeated every 3 months during the first year after transplantation. Enzyme
      linked immunosorbant assay (ELISA) tests were performed on these samples to
      determine if antibodies to EBV antigens, such as viral capsid antigen (VCA)IgM,
      VCAIgG or Epstein Barr neoantigen (EBNA)IgG, were present. The types of
      prescribed immunosuppressive agents and the incidence of acute allograft
      rejection were closely observed to define their association with EBV. EBV
      infection developed in 58 (85.3%) patients and active disease in 10 (14.7%). EBV
      was detected in 40 (58.8%) patients during the first year after transplantation.
      There was EBNAIgG seropositivity in 65 (95.6%) patients before transplantation;
      this number increased to 68 (100%) after transplantation. In contrast, VCAIgG
      seropositivity increased from 92.6% before transplantation to 96.9% after
      transplantation; whereas VCAIgM seropositivity increased from 17.6% before
      transplantation to 58.8% after transplantation. There were no statistically
      significant differences in the reactivation of EBV infection between the
      different immunosuppressive regimens, between the groups of acute rejection and
      no acute rejection, or between the groups that received and did not receive anti
      lymphocyte globulin (ALG). We conclude that most EBV activation after
      transplantation may represent a secondary form of a preexisting infection and we
      could not find a clear association with a specific immunosuppressive regimen,
      including the use of ALG. Further investigation is thus required to elucidate the
      factors involved in the reactivation of the EBV infection in the transplant
      population.

PMID- 16970256
TI  - Survey of the attitude of physicians towards establishing and maintaining a
      peritoneal dialysis program.
AB  - In an attempt to evaluate the attitude of physicians towards establishing and
      maintaining a peritoneal dialysis (PD) program in the Kingdom of Saudi Arabia
      (KSA), we sent a questionnaire to 160 physicians; the heads of the 148 active
      dialysis centers in the KSA and 12 other consultants working in these centers.
      This covered decision makers in 109 centers (73.6%) in the Ministry of Health
      (MOH), 18 (12.2%) in Governmental-non-MOH centers, and 21 (14.2%) in private
      hospitals that, together, care for a population of more than 7300 patients on
      chronic hemodialysis (HD) and 559 on PD. The study was performed between
      September and December 2005. A total of 145 of the 160 physicians (90.6%) from
      141 dialysis centers (95.2%) answered the questionnaire. There were 81
      respondents (56.3%) who believed that follow-up of the PD patients should be
      available in all the dialysis centers, 80 (55.2%) would like to have a PD clinic
      at their centers, and only 20 (13.8%) had PD clinics in their centers. However,
      93 (66.4%) respondents did not request from the administration of their hospitals
      to open a PD clinic and 62 (44.6%) admitted to having no expertise in managing
      the patients on PD, while 53 (38.1%) claimed that they did not have enough space
      in their dialysis centers to start a PD program. Regarding training and
      expertise, 57 (40.7%), 58 (43.3%), 48 (35.6%) and 72 (52.9%) physicians had
      training in continuous ambulatory PD (CAPD), intermittent peritoneal dialysis
      (IPD), automated peritoneal dialysis (APD) or continuous cyclic peritoneal
      dialysis (CCPD), and acute PD, respectively. The comparisons between the health
      sectors in the KSA showed that MOH had significantly less active PD programs, and
      this reflected tremendously on the knowledge of the staff. Our survey indicates
      that the current practices concerning the PD programs in the KSA are modest, and
      that a new strategy is required to spread this modality of therapy horizontally
      in all the dialysis centers, and vertically by introducing the latest
      technologies in the field of PD, such as automated PD machines and connectology.
      There is also a need to increase the awareness of physicians about the benefits
      and applicability of PD. National guidelines and training are indispensable and
      cannot be overemphasized to improve this service, especially in the MOH
      hospitals.

PMID- 16970257
TI  - Darbepoetin use for the treatment of anemia in hemodialysis patients in Saudi
      Arabia.
AB  - Erythropoietin replacing proteins have improved patient outcomes and quality of
      life. Darbepoetin has a 3-fold longer half-life than recombinant human
      erythropoietin (rHuEPO). In this study, we investigate the efficacy and safety of
      the conversion of stable hemodialysis patients from the current short-acting r
      HuEPO (EPO alfa or beta) to the long-acting darbepoetin. In addition, we verified
      the appropriateness of the current ratio of conversion of the short acting to the
      long-acting erythropoietin in an open label prospective multi-center study. The
      study design included 12 weeks darbepoetin administration. The conversion ratio
      was 200 IU of short acting r-HuEPO to 1 microgram of darbepoetin. We adjusted the
      dose of darbepoetin to maintain hemoglobin levels between 110-120 g/L. There were
      33 patients who satisfied the entry criteria. The study was conducted from
      January-June, 2005. The study patients included 18 men and 15 women, the mean age
      was 50.4 +/- 12.3 years and the mean duration on HD was 323 +/- 51.9 days. There
      was a significant decrease in the mean dose of darbepoetin from 37.3 +/- 12.9
      ug/week at week 1 of the study to 20.8 +/- 16.6 ug/week by the end of week 12 (p
      < 0.00003) while the hemoglobin level was maintained within the previously
      defined range. The initial conversion ratio from short-acting erythropoietin to
      darbepoetin was 200 IU to 1 microgram. However, at the end of week 12, the mean
      dose of darbepoetin decreased to an equivalent conversion ratio to 361 IU: 1
      microgram. This may reflect great savings in the cost of treatment. Our
      experience with darbepoetin reveals that darbepoetin is effective and safe for
      the treatment of anemia in hemodialysis patients and has a more convenient dosing
      schedule than short-acting erythropoietin. The darbepoetin dosage decreases over
      time and savings are expected to greater with darbepoetin more than with short
      acting erythropoietin with time.

PMID- 16970258
TI  - Renal osteodystrophy: review of the disease and its treatment.
AB  - Renal osteodystrophy (ROD), which is most evident in patients on renal
      replacement therapy (RRT), usually begins when the kidney function starts to
      deteriorate. The spectrum of skeletal abnormalities seen in ROD is classified
      according to the state of bone turnover. In the past two decades, the prevalence
      of high turnover ROD has decreased while low bone turnover has become
      increasingly recognized. Secondary hyperparathyroidism represents a common
      disorder in patients with chronic kidney disease (CKD); it develops as a result
      of hyperphosphatemia, hypocalcemia and impaired synthesis of renal vitamin D with
      reduction in serum calcitriol levels. Patients with secondary hyperparathyroidism
      have a range of symptoms that affect their quality of life. The aim of treatment
      of ROD is to reduce the incidence of uremic bone disease as well as
      cardiovascular morbidity and mortality caused by elevated serum levels of
      parathormone (PTH) and calcium X phosphorus product. Treatment measures include
      control of phosphorus retention and prevent hyperphosphatemia, maintaining serum
      calcium concentrations within the normal range and prevent excess PTH secretion.

PMID- 16970259
TI  - Fungal abdominal wall abscess in a renal transplant recipient.
AB  - The incidence of fungal infection is significantly higher in patients with
      endstage renal disease and renal transplant recipients than in normal
      individuals. Candidia Albicans is an uncommon cause of abdominal wall abscess. We
      describe a 37 year-old renal transplant recipient with such an infection. He
      presented with atypical clinical manifestations and an insidious course, but was
      successfully treated with antifungal therapy.

PMID- 16970260
TI  - Acute tubulointerstitial nephritis and anterior uveitis (TINU syndrome): a report
      of two cases.
AB  - TINU or Dobrin syndrome is a rare oculo-renal inflammatory condition which is
      comprised of acute idiopathic tubulointerstitial nephritis and uveitis. We report
      here two female patients aged 35 and 44 years, who were admitted with severe
      renal failure of acute onset (serum creatinine of 607 and 310 Umol/L [Editor
      note: do you mean "micromol/L"?] respectively) with the first patient requiring
      hemodialysis. The cause of acute renal failure was unclear on clinical and
      laboratory assessment, and a percutaneous renal biopsy was performed which showed
      features of acute tubulointerstitial nephritis in both cases. Both patients were
      started on oral steroids at a dose of 1 mg/kg/day. There was progressive
      improvement of their renal function. Three months later, the two patients
      presented with bilateral anterior uveitis requiring local corticosteroid therapy.
      This was followed by total resolution of the uveitis. The cause of the
      interstitial nephritis and the uveitis could not be identified in the two cases.
      The renal function was normal in these patients after 24 and 27 months of follow
      up, respectively. Dobrin or TINU syndrome is rare, and must be considered in
      patients who present with acute tubular interstitial [Editor note: for
      consistency with the title, you may wish to replace this with
      "tubulointerstitial"] nephritis and anterior uveitis.

PMID- 16970261
TI  - Hyponatremic hypertensive syndrome in an obese man with renal ischemia.
AB  - Renovascular hypertension occasionally manifests as an electrolyte disorder. The
      combination of hyponatremia and renovascular hypertension is known as
      hyponatremic-hypertensive syndrome. This syndrome was initially reported in
      children. Here, we describe a 45 year-old Saudi man who was admitted to the
      hospital with generalized body weakness and inability to walk. He was confused
      and was noted to have severe hypertension and very low serum sodium and
      potassium. The patient was recently started on captopril for blood pressure
      control, which was discontinued because of deterioration of renal function. Color
      Doppler renal ultrasound, and magnetic resonance angiography confirmed the
      diagnosis of renal artery stenosis.

PMID- 16970262
TI  - Acute renal failure due to lymphomatous infiltration: an unusual presentation.
AB  - Renal lymphoma occurs most often as a part of a multi-systemic disseminated
      lymphoma or as a recurrence of the tumor. Renal involvement usually occurs late
      in the course of the disease and is clinically silent. Acute renal failure (ARF)
      from lymphomatous infiltration has been described but is quite rare. We report a
      50-year-old Caucasian woman, who presented with features of ARF. Physical
      examination showed that her arterial blood pressure was 190/100 mm Hg with no
      lymphadenopathy or hepatosplenomegaly. Her urine output was about 100 ml/day, and
      urinanalysis revealed + proteinuria and microscopic hematuria. Biochemical
      findings revealed severely impaired renal function with a serum creatinine of 693
      micromol/L. The patient's lactate dehydrogenase was elevated at 632 U/L. An
      abdominal ultrasound showed bilateral, large non-obstructed kidneys and a
      hypoechoic mass arising in the right lobe of the liver. An ultrasound-guided
      percutaneous liver biopsy showed typical features of B-cell lymphoblastic
      lymphoma. The patient expired two days later, even before any specific treatment
      could be started.

PMID- 16970263
TI  - Kidney transplantation in Iraq.

PMID- 16970264
TI  - Prevalence and pattern of renal osteodystrophy in chronic hemodialysis patients:
      a cross sectional study of 103 patients.
AB  - This cross sectional study was conducted to determine the prevalence and pattern
      of renal osteodystrophy (ROD) in patients on maintenance hemodialysis (HD) in
      Tripoli, Libya. A total of 103 randomly selected patients, of whom 53% were
      males, were investigated. Their mean age was 47.6 +/- 12.5 years. They were on
      dialysis for a mean duration of 6.2 +/- 4.3 years. Pre-dialysis serum levels of
      intact parathyroid hormone (iPTH), osteocalcin, alkaline phosphatase, albumin,
      total calcium and phosphate were measured in all the patients. Depending on serum
      iPTH levels, the patients were divided into three groups: hyperparathyroid bone
      disease (iPTH > 450 pg/ml), adynamic bone disease (iPTH < 60 pg/ml), and a group
      with apparently normal bone (iPTH 60 pg/ml to 450 pg/ml). As a whole, the mean
      serum levels of iPTH, osteocalcin, alkaline phosphatase and corrected total
      calcium were high in all study patients (373.7 pg/ml, 251.3 ng/ml, 254.9 IU/l,
      and 9.9 mg/dl respectively). The prevalence of ROD among these patients was
      55.3%. Of these, 29 (28.1%) had laboratory evidence of hyperparathyroid bone
      disease, while 28 patients (27.1%) had laboratory evidence of adynamic bone
      disease. In only 18 patients, (17.4%) the serum levels of iPTH were within the
      target range recommended by the K/DOQI guidelines (150-300 pg/ml). This cross
      sectional study, albeit in a limited number of patients, shows that the
      prevalence of ROD in our institution is high, possibly because of inadequate
      patient monitoring and lack of insight into ROD among both patients and
      physicians.

PMID- 16970265
TI  - Incidence and types of malignancies in renal transplant recipients in Iraq.
AB  - We retrospectively reviewed the records of 273 renal transplant recipients who
      received allograft transplants between 1994 and 2004 and recorded the incidence
      and types of de novo malignancies that developed in these patients. The study was
      carried out at the Al-karama and Al-rasheed kidney transplant centers in Baghdad,
      Iraq. A total of 16 patients developed malignancies. The tumors included Kaposi's
      sarcoma (KS) in eight patients, squamous cell carcinoma (SCC) in four, basal cell
      carcinoma (BCC) in two and both renal cell carcinoma of the allograft and brain
      tumor in one patient. Thus, KS was the most common malignancy encountered in our
      series, with a prevalence of 2.9%, followed by SCC observed in 1.5% and BCC found
      in 0.7% of the patients. The average latency period between transplantation and
      development of malignancy was 6.5 months for KS, 3.0 months for SCC and 8.5
      months for BCC. To our knowledge, this is the first long-term follow-up study for
      malignant complications identified in kidney recipients in Iraq.

PMID- 16970267
TI  - Chronic allograft nephropathy.

PMID- 16970266
TI  - Obstructive uropathy in Sudanese patients.
AB  - In this paper we describe the causes, patterns of presentation, and management of
      obstructive uropathy in Sudanese patients in a retrospective multi-center audit.
      All patients who presented with obstructive uropathy during 2005 were included in
      this study. All of the patients were subjected to serial investigations including
      imaging and tests of renal function. Diversion, stenting, and/or definitive
      surgery were performed in order to relieve the obstruction. Five hundred twenty
      patients were diagnosed with obstructive uropathy during this period; 345 (66%)
      patients presented with chronic obstruction and 175 (34%) with acute obstruction.
      Of the study patients, 210 (40%) presented with significant renal impairment; 50
      (23%) of them required emergent dialysis. The patterns of clinical presentation
      of the obstructed patients included pain at the site of obstruction in 48%, lower
      urinary tract symptoms in 42%, urine retention in 36.5%, mass effect in 22%, and
      anuria in 4%. Patients in the pediatric age group constituted 4% of the total.
      The common causative factors of obstruction included congenital urethral valves,
      pelvi-ureteral junction obstruction, urolithiasis, and iatrogenic trauma,
      especially in the obstetric practice. Renal function was completely recovered
      with early management in 100% of patients with acute obstruction and was
      stabilized in 90% of patients with chronic obstruction. Four patients were
      diagnosed with end-stage renal failure; two of them were transplanted. The
      mortality rate in this study was less than 0.3%.

PMID- 16970268
TI  - Dialysis in the Kingdom of Saudi Arabia.

PMID- 16970269
TI  - High-dose norepinephrine induces disruption of myocardial extracellular matrix
      and left ventricular dilatation and dysfunction in a novel feline model.
AB  - BACKGROUND: Intravenous norepinephrine (NE) at a dose of 1-6 microg/kg/minute can
      induce increased extracellular matrix (ECM) and hypertrophic cardiomyopathy. This
      study aimed to investigate the effects of a higher dose of NE on cardiac
      remodeling. METHODS: After intraperitoneal urethane-chloralose anesthesia, 7 cats
      (3.03 +/- 0.58 kg) received intravenous infusion of NE 30 microg/kg/minute for 3
      hours. Aortic blood pressure and heart rate (HR) were measured by polygraphy at
      0, 5, 15, 30, 60, 90, 120, and 180 minutes. Left ventricular size and ejection
      fraction (EF) were measured by M-mode echocardiography before and after NE
      administration. Histopathology was performed by hematoxylin-eosin, silver
      impregnation, and Sirius red staining. Activity of matrix metalloproteinases
      (MMP) in the left ventricle was measured by zymography. RESULTS: Mean blood
      pressure (mmHg) increased from 139 +/- 20 to 198 +/- 19, 187 +/- 23, and 166 +/-
      16 at 15, 30, and 60 minutes, respectively, during NE infusion. HR (beats/minute)
      decreased from 214 +/- 10 to 158 +/- 28 at 15 minutes and then recovered
      gradually. The left ventricles showed significant dilatation (end-diastolic
      diameter: from 1.20 +/- 0.18 to 1.58 +/- 0.23cm, p=0.003; end-systolic diameter:
      from 0.62 +/- 0.23 to 1.35 +/- 0.29cm, p=0.002) and hypokinesia (EF: from 86.2 +/
      5.2 to 33.1 +/- 16.5%, p < 0.001). Histopathology revealed that left ventricular
      myocytes were elongated, wavy, and fragmented, while collagen fibers were
      overstretched, straightened, and disrupted. MMP-9 activity was significantly
      elevated (p = 0.003 vs. control), while MMP-2 activity was unchanged. CONCLUSION:
      High-dose NE increases MMP-9 activity and causes ECM disruption, left ventricular
      dilatation and dysfunction.

PMID- 16970270
TI  - Evaluation of the associations between the single nucleotide polymorphisms of the
      promoter region of the tumor necrosis factor-alpha gene and nasopharyngeal
      carcinoma.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory
      cytokine and may act as an endogenous tumor promoter. Single nucleotide
      polymorphisms (SNPs) of the TNF-alpha gene promoter region have been found to be
      associated with certain cancers. We conducted a case-control study to evaluate
      the association between these SNPs and nasopharyngeal carcinoma (NPC). METHODS:
      We used polymerase chain reaction followed by restriction fragment length
      polymorphism analysis to determine the -308 TNF-alpha promoter genotypes of 89
      NPC patients and 360 healthy controls. In 23 NPC patients and 50 controls, we
      determined the sequence from -1065 to -101 nucleotides of the TNF-alpha gene
      promoter region to detect SNPs. RESULTS: In comparison with the controls, the NPC
      patients had higher proportions of men and carriage of IgA antibodies against the
      capsid antigen of Epstein-Barr virus, but had a similar carrier rate of the -308A
      allele (odds ratio [OR], 1.2; 95% confidence interval [CI], 0.7-2.0). The
      carriage of the -308A allele was not associated with the occurrence of NPC in
      comparison with -308G homozygosity. We also found no significant differences in
      the distributions of allelic variants of the -1031, -863, -857, and -806 loci of
      the TNF-alpha promoter region, but observed a lower carrier rate of the novel 
      806T allele in the NPC patients (OR, 0.3; 95% Cl, 0.0-2.9). CONCLUSION: Allelic
      variants of the TNF-alpha promoter gene may not be used as biomarkers of
      susceptibility to NPC. The role of the -806T allele needs to be studied further.

PMID- 16970271
TI  - Application of upper extremity radionuclide venography as a diagnostic approach
      for Port-A catheter thrombosis.
AB  - BACKGROUND: To investigate the role of upper extremity radionuclide venography as
      a potential diagnostic modality in the assessment of venous thrombosis associated
      with a Port-A catheter. METHODS: Fourteen symptomatic patients who had received
      Port-A catheter implantation were enrolled. A dynamic nuclear medicine flow study
      was performed with intravenous administration of Technetium-99m macroaggregated
      albumin to both upper extremities. Imaging patterns of the venous system were
      categorized as patency, partial obstruction, and total occlusion. RESULTS: The
      findings of the dynamic images clearly demonstrated clinical problems. Three
      patients were free of a definite venous flow change. Three patients had partial
      obstruction of venous return. A significant cut-off of venous return was
      demonstrated in 8 patients, and total occlusions were hence diagnosed. All
      patients underwent this procedure smoothly without any complication. CONCLUSION:
      These results suggest that upper extremity radionuclide venography is an easily
      performed and effective method for diagnosing Port-A catheter thrombosis in
      clinical practice.

PMID- 16970272
TI  - Clinical and histopathologic findings of superficial basal cell carcinoma: A
      comparison with other basal cell carcinoma subtypes.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer in white
      populations. However, BCC is uncommon in Taiwan, and its subtype, superficial BCC
      (SBCC), is even less common. The characteristics of these 2 cancers in Taiwanese
      have never been analyzed before. Our purpose was to study the clinical and
      histopathologic features of SBCC in comparison with other BCC subtypes (OBCC).
      METHODS: Thirty Taiwanese patients with SBCC from 1974 to 2003 were
      retrospectively examined at Taipei Veterans General Hospital. We analyzed the
      age, gender distribution, site of the lesions, clinical appearance, incidence of
      metastasis, and the proportion of secondary amyloid deposits. We then compared
      these features with those of 354 Taiwanese patients with OBCC. RESULTS: Compared
      with the black pearly appearance of OBCC, erythematous plaques or patches with
      multiple tiny blackish papules were the most common clinical appearance of SBCC.
      Tumor size was significantly larger than OBCC (p < 0.05). The trunk was the most
      common area where SBCC arose. Conversely, OBCC occurred mainly on the head and
      neck (p < 0.001). Females were significantly younger than males in both SBCC and
      OBCC groups (p < 0.05). The frequency of secondary amyloid deposits was lower in
      SBCC than OBCC (p < 0.05). CONCLUSION: The unique findings of SBCC would help to
      classify the subtypes of BCC. The mechanism of development of each subtype is
      worth further investigation in the future.

PMID- 16970273
TI  - Comparison between F-18-FDG positron emission tomography and histology for the
      assessment of tumor necrosis rates in primary osteosarcoma.
AB  - BACKGROUND: The purpose of this prospective study was to identify if F-18
      fluorodeoxy-D-glucose positron emission tomography (F-18-FDG PET) was a reliable
      noninvasive surrogate of histologic response in determining the efficacy of
      neoadjuvant chemotherapy before surgical resection in primary osteosarcoma.
      METHODS: Between January 2003 and December 2003, 10 patients with primary
      osteosarcomas were examined using F-18-FDG PET before neoadjuvant chemotherapy
      and surgery. The mean age at the time of first intervention was 19 years (range,
      4-47 years). Positive prognostic significance was defined as more than 90% tumor
      necrosis response following neoadjuvant chemotherapy. The parameters of FDG
      uptake were correlated with histologic findings. The intraclass correlation
      coefficient was used to validate the tumor necrosis rates determined by PET and
      histology. RESULTS: The tumor necrosis rate determined by PET was comparable with
      that determined histologically. The mean standardized uptake value before and
      following neoadjuvant chemotherapy were 8.2 and 4.4, respectively. The average
      tumor necrosis rate determined by PET was 22%. However, the mean tumor necrosis
      rate determined histologically was 54.5%. According to the intraclass correlation
      coefficient models, the intraclass correlation coefficient equaled O. The
      relationship of tumor necrosis rates determined by F-18-FDG PET and histology
      seems to be statistically insignificant. CONCLUSION: In this preliminary study,
      FDG PET did not seem to be a promising tool for evaluating the response of
      primary osteosarcoma to neoadjuvant chemotherapy.

PMID- 16970274
TI  - Management of primary chest wall tumors: 14 years' clinical experience.
AB  - BACKGROUND: Primary chest wall tumor is rare but it encompasses tumors of various
      origins. We analyzed our experience with primary chest wall tumors with emphasis
      on its demographic presentation and management. METHODS: From 1991 to 2004, 62
      patients with the diagnosis of primary chest wall tumors were enrolled. Lipoma,
      chest wall metastasis, direct invasion from nearby malignancy, infection, and
      inflammation of chest wall were excluded. The clinical features, management, and
      the outcome of these patients were retrospectively reviewed. RESULTS: There were
      37 males and 25 females. Malignant and benign tumors were equally distributed.
      Chondrosarcoma and lymphoma were the 2 most common types of malignant chest wall
      tumors. The most common clinical symptoms were palpable mass (54.8%) and pain
      (40.3%). Nine of 31 patients (29.0%) with benign chest wall tumors were free of
      symptoms whereas patients with malignant chest wall tumors were all symptomatic
      (p = 0.002). A definite diagnosis was obtained in 21 of 26 patients (80.7%) who
      received nonexcision biopsy. All patients with primary chest wall tumors, except
      6 who had medical treatment only, underwent surgical resection. Patients with
      malignant chest wall tumors were older than those with benign tumors (p < 0.001).
      The mean largest diameter of tumors was also larger in malignant tumors than in
      benign tumors (p = 0.04). CONCLUSION: Patients with primary malignant chest wall
      neoplasm were older than those with benign tumors. The mean size of malignant
      tumors was larger than that of benign tumors. Adequate surgical resection remains
      the treatment of choice for patients with primary chest wall tumors. Nonexcision
      biopsy should be reserved for patients with a past history of malignancy,
      suspicion of hematologic disease, and with high operative risk. For patients with
      isolated chest wall lymphoma, surgical resection followed by chemotherapy can be
      considered to obtain a better outcome.

PMID- 16970275
TI  - Asymmetric cerebral lesion pattern in X-linked adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy (X-ALD) is an inherited disease caused by
      peroxisomal dysfunction. X-ALD usually involves the cerebral white matter in an
      approximately symmetric way. We report a 10-year-old boy with the cerebral form
      of X-ALD who presented with cognitive impairment and left spastic hemiparesis.
      Brain magnetic resonance imaging (MRI) showed asymmetric lesions, and the lesions
      in the right hemisphere were predominant. In the late stage of the disease,
      bilateral limbs were involved. The cerebral lesions enlarged and appeared
      approximately symmetric on MRI. The purpose of our report is to highlight
      asymmetric demyelination in initial presentation of X-ALD.

PMID- 16970276
TI  - Percutaneous endovascular repair of a ureteroarterial fistula with a stent graft.
AB  - Ureteroarterial fistula is a rare but life-threatening cause of hematuria. The
      predisposing factors of a ureteroarterial fistula includes pelvic exenteration,
      radiation therapy, infection, primary vascular disease, vascular reconstructive
      surgery, and indwelling ureteral catheters or stents. We report a case of
      ureteroarterial fistula between the right ureter and a pseudoaneurysm originating
      from the right proximal external iliac artery in a female patient presenting with
      intermittent massive hematuria. She had previously undergone an operation for
      cervical cancer, radiation therapy, and ureteral stent placement. She was treated
      successfully by percutaneous endovascular stent graft placement to exclude the
      pseudoaneurysm. Percutaneous stent graft placement appears to be an effective and
      safe therapeutic alternative in the treatment of ureteroarterial fistula.

PMID- 16970277
TI  - Pan-urethral wart treated with 5-fluorouracil intraurethral instillation.
AB  - We evaluated whether or not intraurethral instillation of 5-fluorouracil (5-FU)
      solution can rapidly, safely, and effectively eradicate intraurethral condyloma
      acuminata in a human immunodeficiency virus (HIV) carrier. A 43-year-old man
      presented with the major complaint of difficult micturition and blood dribbling
      from the urethral meatus for more than 6 months. He was an HIV carrier for more
      than 10 years and had undergone diathermy for perianal warts. Physical
      examination showed cauliflower lesions over the orifice of the urethra and
      frenulum base of the penile prepuce. Urinalysis disclosed pyuria and microscopic
      hematuria. Cystourethroscopy on the following day showed extensive wart lesions
      extending from the urethra to the bladder neck. Biopsy of the lesions was
      compatible with condyloma acuminata. 5-FU solution (500 mg in normal saline 50
      mL) urethral instillation with massage at the ventral side of the penile shaft
      for 20 minutes was given once a week for 7 doses. The urine routine was normal.
      Management was then prescribed once a month until the lesions became invisible
      under urethroscopy. After 18 doses of 5-FU solution urethral instillation, no
      visible wart lesions were noted. He has been asymptomatic with no voiding
      difficulty for more than 1 year.

PMID- 16970278
TI  - Percutaneous nephroscopic resection of renal pelvic fibroepithelial polyp.
AB  - Benign fibroepithelial polyps of the renal pelvis are extremely rare, and are
      frequently mistaken for transitional cell carcinoma. Diagnosis is usually made
      following nephrectomy or nephroureterectomy for an assumed malignancy of the
      renal pelvis. We report a 56-year-old female with a right renal pelvic
      fibroepithelial polyp successfully treated by percutaneous nephroscopic
      resection.

PMID- 16970279
TI  - Fate of embryonic stem cells transplanted into the deafened mammalian cochlea.
AB  - Spiral ganglion neurons (SGNs), the primary afferent neurons of the cochlea,
      degenerate following a sensorineural hearing loss (SNHL) due to lack of trophic
      support normally received from hair cells. Cell transplantation is emerging as a
      potential strategy for inner ear rehabilitation, as injected cells may be able to
      replace damaged SGNs in the deafened cochlea. An increase in the number of
      surviving SGNs may result in improved efficacy of cochlear implants (CIs). We
      examined the survival of partially differentiated mouse embryonic stem cells
      (MESCs), following xenograft transplantation into the deafened guinea pig cochlea
      (n=15). Cells were delivered directly into the left scala tympani via
      microinjection through the round window. Small numbers of MESCs were detected in
      the scala tympani for up to 4 weeks following transplantation and a proportion of
      these cells retained expression of neurofilament protein 68 kDa in vivo. While
      this delivery method requires refinement for effective long-term replacement of
      damaged SGNs, small numbers of MESCs were capable of survival in the deafened
      mammalian cochlea for up to 4 weeks, without causing an inflammatory tissue
      response.

PMID- 16970280
TI  - Porcine fetal ventral mesencephalic cells are targets for primed xenoreactive
      human T cells.
AB  - Xenotransplantation of porcine fetal ventral mesencephalic (pfVM) cells to
      overcome the dopamine shortage in the striatum of patients with Parkinson's
      disease seems a viable alternative to allotransplantion of human fetal donor
      tissue, especially because the latter is complicated by both practical and
      ethical issues. There is, however, little known about the xenospecific immune
      responses involved in such an intracerebral xenotransplantation. The aim of our
      study was to investigate whether (1) naive human peripheral blood mononuclear
      cells (PMBC) display cytotoxicity against pfVM cells of E28 pig fetuses, and (2)
      priming of human PBMC by xenogeneic antigen presenting cells (APC) modulates pfVM
      directed cellular cytotoxicity. For this purpose fresh PMBC from nine individual
      donors were primed by incubation with either irradiated pfVM cells or porcine
      spleen cells (PSC) as APC in the presence of IL-2 for 1 week before assessing
      cytotoxicity in a 51Cr release assay. Also, direct NK reactivity and antibody
      dependent cellular cytotoxicity (ADCC) of fresh PMBC against pfVM cells was
      assessed. No direct cytotoxicity of naive cells (either NK reactivity or ADCC)
      against pfVM cells could be determined. Only PMBC primed with PSC were capable of
      lysing pfVM cells. PBMC primed with pfVM cells did not show cytolytic capacity
      towards pfVM. Interestingly, large differences in xenospecific T-cell responses
      exist between individual donor PBMC. Thus, human T cells are capable of killing
      pfVM cells in a xenoreactive response, but only after priming by donor APC. The
      large interindividual differences between human donors in their xenoreactive
      response may influence patient selection for xenotransplantation and chances of
      graft survival for individual patients.

PMID- 16970281
TI  - Ectopic ossification in the scar tissue of rats with myocardial infarction.
AB  - We describe the occurrence of bone-like formations in the left ventricular wall
      of infarcted rats treated or not with bone marrow cells injected systemically or
      locally into the myocardium. The incidence of ectopic calcification in hearts has
      been reported in rare cases in children with infarcts without previous coronary
      artery disease. Recently, ventricular calcification has been correlated with
      unselected bone marrow cell transplantation into infarcted rat hearts.
      Echocardiographic analysis of large infarction in rats frequently reveals the
      presence of echogenic structures in the left ventricular wall, sometimes
      projecting to the lumen of the chamber. The histological examination of these
      echogenic structures exhibited bone, cartilage, and marrow-like formations
      extending from the collagen-rich matrix of the ventricle wall. Microanalytical
      techniques verified the presence of hydroxyapatite in the mineral phase.
      Ossification was found in 25 out of 30 hearts evaluated 90 days postinfarct,
      being observed in 14 out of 17 animals submitted to cell therapy and in 11 out of
      13 infarcted rats not submitted to cell therapy. Our study indicates that chondro
      osteogenic differentiation can take place in the pathological rat heart
      independent of animal treatment with marrow cells.

PMID- 16970282
TI  - Suppression of human T-cell responses to beta-cells by activation of B7-H4
      pathway.
AB  - B7-H4, a recently described member of the B7 family of cosignal molecules, is
      thought to be involved in the regulation of cellular and humoral immune responses
      through receptors on activated T and B cells. Human islet cells express positive
      B7-H4 mRNA in RT-PCR assays, but not B7-H4 protein on cell surface in flow
      cytometric analyses. To investigate the regulatory effects of activation of the
      B7-H4 pathway on the function of activated T cells of patients with type 1
      diabetes (T1D), we have used our in vitro human experimental system, including
      human beta-cell antigen-specific T-cell clones and human beta-cell lines CM and
      HP62, as well as primary islet cells. B7-H4.Ig protein was purified from the
      culture supernatant of 293T cells transfected by a B7-H4.Ig plasmid (pMIgV,
      containing a human B7-H4 cDNA and a mouse IgG2a Fc cDNA). Our preliminary studies
      showed that immobilized fusion protein human B7-H4.Ig (coated with 5 microg/ml
      for 2 h at 37 degrees C), but not control Ig, clearly inhibited the proliferation
      of activated CD4+ and CD8+ T cells of patients induced by anti-CD3 antibody in
      CFSE assays. B7-H4.Ig also arrested cell cycle progression of T cells in G0/G1
      phase and induced T-cell apoptosis as measured by BrdU-7-AAD flow cytometric
      analysis. To determine the cytoprotective effects of B7-H4, we developed
      transfectants of human beta-cell lines CM and HP62 and islet cells transfected
      with the B7-H4.Ig plasmid, using empty vector transfectants as controls. The
      results demonstrate that cell-associated B7-H4.Ig expressed on human beta-cells
      clearly inhibits the cytotoxicity of the T-cell clones to targeted human beta
      cells in 51Cr release cytotoxicity assays. Activation of the B7-H4 pathway may
      represent a novel immunotherapeutic approach to inhibit T-cell responses for the
      prevention of beta-cell destruction in T1D.

PMID- 16970283
TI  - Regeneration of osteonecrosis of canine scapho-lunate using bone marrow stromal
      cells: possible therapeutic approach for Kienbock disease.
AB  - We evaluated the ability of canine bone marrow stromal cells (cBMSCs) to
      regenerate bone in a cavity of the scapholunate created by curretage and freeze
      thawing with liquid nitrogen (LN). Autologous BMSCs were harvested from the iliac
      crest and expanded in vitro. Their potential to differentiate into osteo-,
      chondro-, and adipogenic lineages was confirmed using a standard differentiation
      induction assay. LN-treated scapholunates showed no regeneration of bone tissue
      when the cavity was left alone, demonstrating severe collapse and deformity as
      observed in human Kienbock disease. A combination of beta-tri-calcium phosphate
      and a vascularized bone graft with autologous fibroblasts failed to regenerate
      bone in the LN-treated cavity. When the same procedure was performed using BMSCs,
      however, LN-treated scapholunates showed no collapse and deformity, and the
      cavity was completely filled with normal cancerous bone within 4 weeks. These
      results suggested the potential of using BMSCs to treat Kienbock disease.

PMID- 16970284
TI  - Assessment of in vitro applicability of reversibly immortalized NKNT-3 cells and
      clonal derivatives.
AB  - In vitro applications of human hepatocytes, such as bioartificial livers and
      toxicity assays, require thoroughly testing of human cell lines prior to using
      them as alternative cell sources. The reversibly immortalized NKNT-3 cell line
      was reported to show clear in vivo functionality. Here, NKNT-3 cells were tested
      for their in vitro applicability. Low-passage (P2) and high-passage (P28) NKNT-3
      cells and clonal derivatives were characterized for reversion of immortalization,
      heterogeneity, and hepatic functionality. Reversion with reduced expression of
      immortalizing agent could be established. However, during culturing the cells
      lost the capacity to be selected for completed reversion. The phenotypic
      instability is probably associated with heterogeneity in the culture, as clonal
      derivatives of P2 cells varied in morphology, growth, and reversion
      characteristics. The mRNA levels of genes related with hepatic differentiation
      increased 4-20-fold after reversion. However, the levels never exceeded 0.1% of
      that detected in liver and no urea production nor ammonia elimination was
      detected. Additionally, activities of different cytochrome P450s were limited. In
      conclusion, the NKNT-3 culture is heterogeneous and unstable and the in vitro
      functionality is relatively low. These findings emphasize that in vivo testing of
      hepatic cell lines is little informative for predicting their value for in vitro
      applications.

PMID- 16970285
TI  - A novel bioreactor microcarrier cell culture system for high yields of
      proliferating autologous human keratinocytes.
AB  - Rapid and efficient resurfacing of various skin defects by autologous
      keratinocyte transplantation is significant in skin wound healing. We developed a
      novel bioreactor microcarrier cell culture system (Bio-MCCS) to produce
      autologous human keratinocytes on a large scale. In this Bio-MCCS we used porcine
      gelatin microbeads as microcarriers for autolgous keratinocytes and spinning
      bottles as fermentation tanks. First, the microbeads were modified by culturing
      them with autologous dermal fibroblasts that were subsequently killed when they
      proliferated to confluence on the microbeads. We then performed the Bio-MCCS by
      expanding ketatinocytes on the microbeads in spinning bottles at 37 degrees C, 5%
      CO2. Our results showed that keratinocytes rapidly attached to and actively
      proliferated on the modified microbeads in the Bio-MCCS, achieving high cell
      densities on the modified microbeads (MTT assay and PI staining). Keratinocytes
      cultured on the modified microbeads in the Bio-MCCS remained proliferating
      potentials as shown by positive PCNA staining and BrdU labeling. In contrast,
      keratinocytes cultured on nonmodified microbeads in the Bio-MCCS proliferated
      slowly, rapidly ceased to proliferate, and finally dislodged from the microbeads.
      When removed from the Bio-MCCS and cultured under static conditions,
      keratinocytes were able to leave the modified microbeads and formed a
      multilayered epidermal equivalent on the culture surfaces. While stored at room
      temperature, keratinocytes remained at higher viabilities on the modified
      microbeads when compared to those on nonmodified microbeads. The achievement of
      high yields of proliferating autologous keratinocytes by this Bio-MCCS offers a
      practical potential of resurfacing various skin defects by direct administration
      of autologous keratinocyte microbeads on various skin defects.

PMID- 16970287
TI  - Managing lung cancer in developing countries: difficulties and solutions.

PMID- 16970286
TI  - High yields of autologous living dermal equivalents using porcine gelatin
      microbeads as microcarriers for autologous fibroblasts.
AB  - Permanent skin replacement requires a dermal component to ensure adequate long
      term graft stability and to prevent wound contraction. This study was to
      construct a bioreactor microcarrier cell culture system (Bio-MCCS) to produce
      autologous living dermal equivalents on a large scale. Autologous fibroblasts
      were isolated from split-thickness skin biopsy from a leg ulcer patient,
      inoculated onto macroporous porcine gelatin microbeads, and incubated in a
      bioreactor (Cellspin) in serum-free fibroblast growth medium or in DMEM medium
      containing 10% fetal calf serum (FCS). Fibroblasts rapidly adhered to and
      actively proliferated on the microbeads in the bioreactor in both serum-free and
      serum-containing medium. MTT assay showed the number of fibroblasts on the
      microbeads reached up to 5.3- or 4.0-fold the cells seeded in DMEM medium
      containing 10% FCS or serum-free medium, respectively. When removed from Bio-MCCS
      and cultured under static conditions, fibroblasts were able to leave the
      microbeads and proliferate to confluence on the bottom of tissue culture flasks.
      When stored at room temperature in DMEM containing 10% FBS, fibroblast cultured
      on the microbeads retained highest viabilities for at least 3 weeks, up to 82% of
      originals. This Bio-MCCS using porcine gelatin microbeads as carriers for
      fibroblasts offers a new option of mass production of autologous living dermal
      equivalents.

PMID- 16970288
TI  - The challenges of tuberculosis.

PMID- 16970289
TI  - Is routine mediastinoscopy indicated for patients with T1 non-small cell lung
      cancer?
AB  - OBJECTIVE: Mediastinoscopy is gold standard in the staging patients with non
      small cell lung cancer (NSCLC) patients. Yet, its necessity in every patient is
      being questioned as new data is being collected. In the present study, we
      compared pathology reports of the cases with T1 NSCLC both after mediastinoscopy
      and thoracotomy, and discussed about the necessity of mediastinoscopy. METHODS:
      We retrospectively reviewed the records of 74 patients (73 patients with
      pathologic T1 NSCLC patients who underwent pulmonary resection and one patient
      clinically T1 who did not undergo pulmonary resection), between 1996 and 2002.
      Clinically 80% of the cases were at T1 stage, and the rest were at T2 stage. The
      distribution of clinical lymph node status was NO in 85%, 15% N2. RESULTS: Fifty
      three (71.6%) cases underwent mediastinoscopy. Mediastinoscopy showed that one
      patient had contralateral lymph node involvement and the remaining cases had no
      lymph node metastases. No mortality occurred and morbidity rate was 1.9%.
      Lobectomy was performed in 60 cases, pneumonectomy in seven, wedge resection in
      five, and segmentectomy in one. The histopathologic types were; squamous cancer
      in 40 (55%) cases, adenocarcinoma in 29 (40%), and large cell carcinoma in four
      (5%). Only two cases (2.7%) who had no detectable lymph node metastases at
      mediastinoscopy were found to have N2 disease after thoracotomy. In rest of the
      cases, NO was observed in 48 (66%) and N1 in 23 (31.5%). Five-year survival of
      the cases was calculated to be 73%. The two cases with N2 disease are alive at
      seven and four years after the operation. CONCLUSION: Routine mediastinoscopy
      does not appear to be necessary for patients with clinical T1 non-small cell
      carcinoma having no enlarged lymph nodes on computerised tomography.

PMID- 16970290
TI  - A five-year review of tuberculosis mortality amongst hospitalised patients in Ile
      Ife.
AB  - BACKGROUND: Death from tuberculosis (TB) is the longest recorded indicator of the
      TB epidemic in industrialised countries. This study aims at investigating into
      various factors associated with death in hospitalised patients with tuberculosis
      in Ile-Ife, Nigeria. METHODS: A retrospective study of all admissions into the
      medical wards, total number of deaths and number of cases of deaths due to TB
      during the period 1998-2000 was done. RESULTS: Tuberculosis represented 8% (268)
      of all admissions (n=3464). The overall hospital mortality during the period
      under review was 1030 (30%). Tuberculosis was responsible for 5% of all deaths
      while TB specific mortality was 18.3 percent. The highest mortality was observed
      among patients between the 3rd and 4th decade of life with a male to female ratio
      1.3: 1. About 70% of the patients died within a week of admission. Pulmonary TB
      was responsible for 69% of deaths followed by tuberculous meningitis (14%),
      retroviral illness (24%), anaemia (60%). Delayed presentation and diagnosis were
      identified as factors commonly associated with death rate. CONCLUSIONS: Delayed
      presentation and diagnosis were commonly associated with death. There is a need
      for more awareness among patients and health care providers about tuberculosis.

PMID- 16970291
TI  - Pleurocutaneous flap: how useful it is in management of chronic empyema.
AB  - BACKGROUND: Definitive surgical treatment of chronic empyema is associated with
      considerable morbidity and mortality. Methods. Retrospective study of 50 patients
      with chronic empyema who underwent pleurocutaneous flap procedure during the
      period 1994 to 2003. RESULTS: Their age ranged from 14 to 70 years; there were 32
      males. Thirty-seven (74%) patients were on intercostal tube drainage; nine (18%)
      presented with bronchopleural fistula; and four (8%) had past-pneumonectomy
      empyema. Following pleurocutaneous flap procedure, 28 (56%) responded with re
      expansion of the lung; 15 (30%) had persistence of pus discharge and air-leak
      suggestive of bronchopleural fistula. Definitive surgery could be undertaken in
      nine of the 15 patients. CONCLUSIONS: Pleurocutaneous flap procedure renders the
      patient ambulatory, facilitates re-expansion of the lung and helps as a tide-over
      procedure before definitive surgery in patients with chronic empyema.

PMID- 16970292
TI  - Aetiology and clinical profile of spontaneous pneumothorax in adults.
AB  - BACKGROUND: Limited information is available on epidemiology of spontaneous
      pneumothorax (SP) from India. The present study was aimed at studying aetiology
      and clinical profile of patients with SP. METHODS: All patients admitted at a
      tertiary care hospital with the diagnosis of SP between January 2001 and March
      2002 were prospectively studied. Detailed demographic and clinical data were
      recorded. Patients were divided into two groups-primary spontaneous pneumothorax
      (PSP), if no underlying aetiology for pneumothorax was found, and secondary
      spontaneous pneumothorax (SSP), when an underlying respiratory disorder could be
      identified. The clinical features were compared between the two groups. RESULTS:
      Sixty patients (12 with PSP and 48 with SSP) were included in the study. Annual
      incidence of SP was calculated as 99.9 per 100,000 hospital admissions. Annual
      incidence figures for PSP and SSP were 20.0 and 80.0 per 100,000 hospital
      admissions respectively. Age distribution showed a biphasic pattern and the
      overall male to female ratio was 5 : 1. The most common cause of SSP was found to
      be pulmonary tuberculosis (41.7%). CONCLUSIONS: Pneumothorax is more common among
      men. In India, SSP is far more common than PSP, and the predominant underlying
      cause is pulmonary tuberculosis.

PMID- 16970293
TI  - Role of bronchoscopy in early diagnosis of lung cancer.
AB  - Lung cancer is a leading cause of cancer deaths and the incidence is rising. Most
      patients with lung cancer present to the clinician in a fairly advanced stage and
      at best only 25-30% of patients can be offered curative resection. Screening
      tests using sputum cytology and chest radiograph have been used with limited
      success. Value of low dose spiral CT scan as screening tool for lung cancer is
      being evaluated and its limitations include high costs, need for repeated
      scanning and necessity to obtain histological confirmation with additional
      procedures. There have been significant advances in the early diagnosis of lung
      cancer in high risk patient groups using bronchoscopic methods such as white
      light bronchoscopy, autofluorescence bronchoscopy, high magnification
      bronchoscopy, narrow band imaging and endobronchial ultrasound. These techniques
      appear to be promising tools as they might allow to visualise changes of early
      lung cancer and also permit sampling for histological confirmation.

PMID- 16970294
TI  - High intensity exercise training programme following cardiac transplant.
AB  - A 26-year-old male patient who presented with symptoms of end stage cardiac
      failure as a result of dilated cardiomyopathy, had an orthotopic cardiac
      transplantation. A comprehensive cardiac rehabilitation programme was provided to
      him and he was introduced to a sport (tennis). The exercise training programme
      progressed from low intensity training to high intensity programme over a period
      of 15 months. A cardio-pulmonary exercise test done 22 months after surgery
      suggested that he was able to achieve the aerobic capacity comparable to that of
      a normal South Indian subject. He participated successfully in the World
      Transplant Games in Sydney and returned safely. This suggests that after a proper
      cardiac rehabilitation programme, patients undergoing heart transplantation can
      achieve normal physiological responses to lead a normal active life.

PMID- 16970295
TI  - Superior vena cava syndrome caused by pulmonary amoebic abscess.
AB  - Isolated pulmonary amoebiasis without involvement of liver and other systems is
      extremely rare. Its presentation with superior vena cava (SVC) syndrome is not
      well documented. The case of 38-year-old male who developed SVC syndrome due to a
      large pulmonary amoebic abscess, which initially mimicked a pulmonary neoplasm
      with distal lung abscess is presented here. Subsequent bacteriological
      examination of the aspirated pus and the sputum along with suggestive serology
      confirmed the diagnosis of pulmonary amoebic abscess.

PMID- 16970296
TI  - Uncommon parathyroid mediastinal cyst compressing the trachea.
AB  - Mediastinal parathyroid cyst is a rare cause of space occupying lesion in the
      mediastinum. No specific symptomatology may be attributed to the non-functioning
      parathyroid cyst. The diagnosis is rarely made before exploration. The cysts are
      thin walled, smooth, of varying sizes and contained clear, opalescent or
      haemorrhagic fluid. Histopathological examination reveals clusters of parathyroid
      cells dispersed in the wall of the cyst. Surgical removal is the treatment of
      choice and can be performed with minimal morbidity.

PMID- 16970297
TI  - Pulmonary hyalinizing granuloma with ureteric fibrosis: A case report and review
      of relevant literature.
AB  - A 52-year-old, asymptomatic patient presented with bilateral lung nodules on
      chest radiograph. She was diagnosed to have "pulmonary hyalinizing granuloma" on
      an open lung biopsy. We review the clinical features of this rare disease.

PMID- 16970298
TI  - Life threatening exacerbation in idiopathic pulmonary hemosiderosis salvaged by
      cyclophosphamide infusion.
AB  - A seven-year-old girl presented with frequent fever, cough and shortness of
      breath of three months duration. On the basis of her clinical features,
      peripheral blood and sputum findings, she was diagnosed as a case of idiopathic
      pulmonary hemosiderosis. After initial stabilisation with steroids and
      chloroquine, she presented four years later with massive pulmonary hemorrhage and
      respiratory failure, which responded dramatically to cyclophosphamide infusion.
      The rare occurrence of pulmonary hemosiderosis and different treatment regimens
      is discussed.

PMID- 16970299
TI  - Epithermal neutron activation analysis of Cr(VI)-reducer basalt-inhabiting
      bacteria.
AB  - Epithermal neutron activation analysis (ENAA) has been applied to study elemental
      composition of Cr(VI)-reducer bacteria isolated from polluted basalts from the
      Republic of Georgia. Cr(VI)-reducing ability of the bacteria was examined by
      electron spin resonance, demonstrating that the bacteria differ in their rates of
      Cr(VI) reduction. A well-pronounced correlation between the ability of the
      bacteria to accumulate Cr(V) and their ability to reduce Cr(V) to Cr(III)
      observed in our experiments is discussed. Elemental analysis of these bacteria
      also revealed that basalt-inhabiting bacteria are distinguished by relative
      contents of essential elements such as K, Na, Mg, Fe, Mn, Zn, and Co. A high rate
      of Cr(III) formation correlates with a high concentration of Co in the bacterium.
      ENAA detected some similarity in the elemental composition of the bacteria. The
      relatively high contents of Fe detected in the bacteria (140-340 microg/g of dry
      weight) indicate bacterial adaptation to the environmental conditions typical of
      the basalts. The concentrations of at least 12-19 different elements were
      determined in each type of bacteria simultaneously starting with the major to
      ultratrace elements. The range of concentrations spans over 8 orders of
      magnitude.

PMID- 16970301
TI  - Automated target preparation for microarray-based gene expression analysis.
AB  - DNA microarrays have rapidly evolved toward a platform for massively paralleled
      gene expression analysis. Despite its widespread use, the technology has been
      criticized to be vulnerable to technical variability. Addressing this issue,
      recent comparative, interplatform, and interlaboratory studies have revealed
      that, given defined procedures for "wet lab" experiments and data processing, a
      satisfactory reproducibility and little experimental variability can be achieved.
      In view of these advances in standardization, the requirement for uniform sample
      preparation becomes evident, especially if a microarray platform is used as a
      facility, i.e., by different users working in the laboratory. While one option to
      reduce technical variability is to dedicate one laboratory technician to all
      microarray studies, we have decided to automate the entire RNA sample preparation
      implementing a liquid handling system coupled to a thermocycler and a microtiter
      plate reader. Indeed, automated RNA sample preparation prior to chip analysis
      enables (1) the reduction of experimentally caused result variability, (2) the
      separation of (important) biological variability from (undesired) experimental
      variation, and (3) interstudy comparison of gene expression results. Our robotic
      platform can process up to 24 samples in parallel, using an automated sample
      preparation method that produces high-quality biotin-labeled cRNA ready to be
      hybridized on Affymetrix GeneChips. The results show that the technical
      interexperiment variation is less pronounced than with manually prepared samples.
      Moreover, experiments using the same starting material showed that the automated
      process yields a good reproducibility between samples.

PMID- 16970300
TI  - Electrochemical detection of arsenic(III) using iridium-implanted boron-doped
      diamond electrodes.
AB  - Iridium-modified, boron-doped diamond electrodes fabricated by an ion
      implantation method have been developed for electrochemical detection of arsenite
      (As(III)). Ir+ ions were implanted with an energy of 800 keV and a dose of 10(15)
      ion cm(-2). An annealing treatment at 850 degrees C for 45 min in H2 plasma (80
      Torr) was required to rearrange metastable diamond produced by an implantation
      process. Characterization was investigated by SEM, AFM, Raman, and X-ray
      photoelectron spectroscopy. Cyclic voltammetry and flow injection analysis with
      amperometric detection were used to study the electrochemical reaction. The
      electrodes exhibited high catalytic activity toward As(III) oxidation with the
      detection limit (S/N = 3), sensitivity, and linearity of 20 nM (1.5 ppb), 93 nA
      microM(-1) cm(-2), and 0.999, respectively. The precision for 10 replicate
      determinations of 50 microM As(III) was 4.56% relative standard deviation. The
      advantageous properties of the electrodes were its inherent stability with a very
      low background current. The electrode was applicable for analysis of spiked
      arsenic in tap water containing a significant amount of various ion elements. The
      results indicate that the metal-implanted method could be promising for
      controlling the electrochemical properties of diamond electrodes.

PMID- 16970302
TI  - Quantitative method for analysis of monensin in soil, water, and urine by direct
      combination of single-drop microextraction with atmospheric pressure matrix
      assisted laser desorption/ionization mass spectrometry.
AB  - A simple and selective analytical method for the quantitative determination of
      low concentrations of monensin in soil, surface water, and human urine has been
      developed. Prior to atmospheric pressure matrix-assisted laser
      desorption/ionization mass spectrometry (AP-MALDI-MS) analysis, the samples were
      preconcentrated by using the single-drop microextraction (SDME) technique.
      Several factors that affect the analyte's extraction, including selection of
      solvent, microdrop volume, extraction time, and ionic strength, were
      investigated. Chloroform-toluene (1:1, v/v) was selected as the extraction
      solvent. Reliable results were obtained using dibenzo-30-crown-10-ether as an
      internal standard. The proposed method has been successfully applied for the
      determination of monensin in soil, surface water, and human urine spiked samples.
      Under the optimized conditions, the limits of quantification of the analyte in
      surface water, soil, and human urine were 6.7, 12.4 and 7.8 ng/mL, respectively.
      The intraday and interday precision variation and accuracy of the present method
      is within the acceptable ranges. The present method avoids the pre- and
      postderivatization of weak UV absorbing monensin determination using high
      performance liquid chromatography-ultraviolet detection (HPLC-UV). Furthermore,
      these techniques are time-consuming, nonreproducible at trace levels, and form
      undesirable products. The proposed SDME combined with AP-MALDI-MS is simple,
      fast, and selective for the determination of monensin in environmental and urine
      samples.

PMID- 16970303
TI  - Cubic phase content and structure of BN films from an X-ray absorption study.
AB  - X-ray absorption near-edge structure (XANES) was used to study the cubic boron
      nitride (c-BN) content in the BN films deposited on various substrates by
      different physical vapor deposition or plasma-enhanced chemical vapor deposition
      methods. By fitting the XANES curves of thin-film samples using standard spectra
      of pure c-BN and sp(2)-bonded BN in the films with suitable weight factors, the c
      BN contents at the film's surface region and across the film's thickness have
      been determined quantitatively. The results agree well with the previous
      transmission electron microscopic observations. The method is proved to be
      independent of the optical properties of thin film and provides a possibility to
      evaluate the cubic content of BN films accurately.

PMID- 16970304
TI  - Isotopic analysis of atmospheric formaldehyde by gas chromatography isotope ratio
      mass spectrometry.
AB  - Little is known about the isotopic composition of formaldehyde in the atmosphere,
      a chemical intermediate in hydrocarbon oxidation. Here, we present a promising
      new method to analyze the carbon (delta 13C) and hydrogen (delta D) isotopic
      composition of atmospheric formaldehyde. The direct isotopic analytical technique
      described uses continuous-flow gas chromatography-isotope ratio mass
      spectrometry, which provides flexibility for either isotopic analysis without
      correction for derivative functional groups. Current levels of precision of
      measurement are +/-1.1 and +/-50 per thousand (1 sigma) for delta 13C and delta D
      analyses, respectively. Concentration of formaldehyde in ambient air is also
      determined, coincident with isotopic measurement, to a precision of +/-15%. The
      method has the required sensitivity for analyses of formaldehyde in urban air on
      relatively small volume grab samples of whole air (10-70L STP), potentially
      providing high temporal resolution. This is particularly advantageous for
      studying formaldehyde given its short lifetime and large variability in the
      atmosphere.

PMID- 16970305
TI  - Protease amperometric sensor.
AB  - An amperometric biosensor for the detection of trypsin was developed. The latter
      was based on a two-layer configuration, namely, a polymer-glucose oxidase inner
      layer and a gelatin outer layer. In the presence of glucose, the enzyme layer
      produces H2O2 and hence an amperometric signal due to H2O2 electrooxidation was
      generated by potentiostating the electrode at 0.6 V. The biosensor detects the
      change in the increase in the maximum current caused by the proteolytic digestion
      of gelatin, which covers the platinum electrodes, thereby facilitating a speedier
      access for the glucose substrate to the electrode modified with both poly(pyrrole
      alkylammonium) and glucose oxidase molecules. Our biosensor detected low trypsin
      concentrations down to 42 pM with a response time of approximately 10 min, making
      it a very sensitive device in the detection of lower trypsin levels with such
      future putative applications as the diagnosis of pancreatic diseases.

PMID- 16970306
TI  - Electrochemical biosensor based on integrated assembly of dehydrogenase enzymes
      and gold nanoparticles.
AB  - Development of a highly sensitive nanostructured electrochemical biosensor based
      on the integrated assembly of dehydrogenase enzymes and gold (Au) nanoparticle is
      described. The Au nanoparticles (AuNPs) have been self-assembled on a thiol
      terminated, sol-gel-derived, 3-D, silicate network and enlarged by hydroxylamine
      seeding. The AuNPs on the silicate network efficiently catalyze the oxidation of
      NADH with a decrease in overpotential of approximately 915 mV in the absence of
      any redox mediator. The surface oxides of AuNP function as an excellent mediator,
      and a special inverted "V" shape voltammogram at less positive potential was
      observed for the oxidation of NADH. The AuNP self-assembled sol-gel network
      behaves like a nanoelectrode ensemble. The nanostructured electrode shows high
      sensitivity (0.056 +/- 0.001 nA/nM) toward NADH with an amperometric detection
      limit of 5 nM. The electrode displays excellent operational and storage
      stability. A novel methodology for the fabrication of a NADH-dependent
      dehydrogenase biosensor based on the integration of dehydrogenase enzyme and
      AuNPs with the silicate network is developed. The enzymatically generated NADH
      is, in turn, electrocatalytically detected by the AuNPs on the silicate network.
      The integrated assembly has been successfully used for the amperometric
      biosensing of lactate and ethanol at a potential of -5 mV. The biosensor is very
      stable and highly sensitive, and it has a fast response time. The excellent
      performance validates the integrated assembly as an attractive sensing element
      for the development of new dehydrogenase biosensors.

PMID- 16970307
TI  - Electropolymerization on microelectrodes: functionalization technique for
      selective protein and DNA conjugation.
AB  - A critical shortcoming of current surface functionalization schemes is their
      inability to selectively coat patterned substrates at micrometer and nanometer
      scales. This limitation prevents localized deposition of macromolecules at high
      densities, thereby restricting the versatility of the surface. A new approach for
      functionalizing lithographically patterned substrates that eliminates the need
      for alignment and, thus, is scalable to any dimension is reported. We show, for
      the first time, that electropolymerization of derivatized phenols can
      functionalize patterned surfaces with amine, aldehyde, and carboxylic acid groups
      and demonstrate that these derivatized groups can covalently bind molecular
      targets, including proteins and DNA. With this approach, electrically conducting
      and semiconducting materials in any lithographically realizable geometry can be
      selectively functionalized, allowing for the sequential deposition of a myriad of
      chemical or biochemical species of interest at high density to a surface with
      minimal cross-contamination.

PMID- 16970309
TI  - Determination of the capacitance of solid-state potentiometric sensors: An
      electrochemical time-of-flight method.
AB  - A dual microelectrode electrochemical time-of-flight technique in which diffusion
      flux of Ag+, Cl-, or H+ ions electrochemically produced at a generator electrode
      is measured by recording potential-time transients with Ag, Ag/AgCl, or iridium
      oxide potentiometric microsensors, respectively, is developed. The generator and
      microsensor electrodes are typically spaced by 50-100 microm and are incorporated
      in the lithographically fabricated thin-layer-type devices. Under conditions of
      moderate rates of the ion electrogeneration, the potential-time (E-t) transients
      recorded with the three microsensors show excellent agreement with theory
      involving linear diffusion equations and the experimentally determined Nernstian
      slopes of the microsensors. However, when the generator current, or the initial
      concentration of the primary ion of interest is low, appreciable delays in the
      recorded E-t transients are observed due to the finite capacitance of the
      micropotentiometric sensors. The recorded delay in the E-t transients can be
      quantitatively accounted for by including the sensor capacitance (C) in the
      theoretical description of the transients. Direct comparison between the
      theoretical and the experimental E-t transients yields the sensor's capacitance.
      This capability of our new technique is unique in that it allows determination of
      the capacitance of a potentiometric sensor at open circuit. In the cases of
      silver electrodes, this method results in C = 31 +/- 2 microF/cm2, a value that
      is in agreement with those obtained by other methods. The results for silver
      chloride sensors yield a C in the range of 100-140 +/- 10 microF/cm2. The
      specific values depend on sensor preparation and the resulting roughness of the
      Ag/AgCl interface. Iridium oxide sensors show a capacitance that linearly depends
      on the thickness of the film. Specific capacitance of these microporous films was
      determined to be 59 +/- 6 F/cm3.

PMID- 16970308
TI  - Microelectrode array biochip: tool for in vitro drug screening based on the
      detection of a drug effect on dopamine release from PC12 cells.
AB  - Novel, yet simple detection techniques of drug effect, including the effect of a
      vesicular monoamine transporter inhibitor (reserpine), a dopamine precursor (L
      dopa), and a dopamine transporter inhibitor (nomifensine), on dopamine release
      from dopaminergic PC12 cells were developed based on a microelectrode array (MEA)
      biochip. Upon multi-injections of KCl solution into the culture of PC12 cells
      attached on a MEA biochip, the K+-stimulated dopamine release was temporally and
      amperometrically recorded by biochip microelectrodes. Two parameters in the
      recorded amperometric spectra were defined in this study: the peak current of the
      first KCl injection (Max1), and the steady current after the fourth KCl injection
      (St4). Statistically significant effects of L-dopa and reserpine were
      demonstrated by comparing both Max1 and St4 of the second detections in drugs
      with those of the control without drug treatment. The values of both Max1 and St4
      in the first detections were normalized as 1. In contrast, the statistically
      significant effect of nomifensine was detected by comparing the ratios of St4 to
      Max1 in the first detections in drug with those of the control. The reason for
      using different analytical methods for measurements between L-dopa/reserpine and
      nomifensine lies in the different mechanisms of action on PC12 cells among these
      drugs. The novel analytical methods developed use the same detection setup and
      parameters, and the data analysis for the effect of drugs becomes simple. The
      methods hence may provide a high-throughput in vitro drug screening approach for
      dopamine-related psychiatric disorders.

PMID- 16970310
TI  - Comprehensive gas chromatography-time-of-flight mass spectrometry using soft and
      selective photoionization techniques.
AB  - The hyphenation of gas chromatography and mass spectrometry (GC/MS)
      revolutionized organic analysis. In GC/MS coupling, usually electron impact
      ionization is applied, and molecules are identified by their fragment pattern.
      Although mass spectrometry in principle is a separation method, it is used
      predominantly as a spectrometric technique. However, if soft (i.e., fragmentation
      free) ionization techniques are applied, the inherent separation character of MS
      is emphasized, which has similarities to a GC boiling point separation. By
      combining polar column GC separation and fast soft ionization time-of-flight mass
      spectrometry technology, a comprehensive separation of complex petrochemical
      samples can be obtained (GC x MS approach). Compounds of comparable physical
      chemical properties are characteristically grouped together in a two-dimensional
      retention time-m/z representation. This resembles the separation characteristics
      of comprehensive two-dimensional gas chromatography (GC x GC) and, thus,
      represents a novel multidimensional separation approach. In this work, a gas
      chromatograph equipped with a polar separation column was coupled to a home-built
      laser ionization time-of-flight mass spectrometer. Laser-based, single-photon
      ionization was used for universal soft ionization and resonance-enhanced
      multiphoton ionization for selective ionization of aromatic compounds. A novel
      capillary-jet inlet system was used for the coupling. Multidimensional
      comprehensive analysis of complex petrochemical hydrocarbon samples using gas
      chromatography coupled to mass spectrometry with soft and selective photo
      ionization sources is first demonstrated.

PMID- 16970311
TI  - Nanophase-separated amphiphilic conetworks as versatile matrixes for optical
      chemical and biochemical sensors.
AB  - As a novel class of sensor matrixes, nanophase-separated amphiphilic polymeric
      conetworks (APCNs) open a new dimension for optical chemical and biochemical
      sensing. These conetworks consist of a hydrophilic phase-we used poly(2
      hydroxyethyl acrylate), poly(2-(dimethylamino)ethyl acrylate), or polycationic
      poly(2-(trimethylammonium)ethyl acrylate)-and of a hydrophobic phase
      poly(dimethylsiloxane). Sensors can be prepared by simple impregnation of the
      matrix. Due to nanophase separation, there is a spatial separation between areas
      in which the indicator reagents are well immobilized and areas that
      advantageously take care of the diffusive transport of the analyte, whereby these
      functionalities of the contrary phases can be exchanged. Thanks to the huge
      interface between the contrary phases, the accessibility of the indicator
      reagents is good, which makes it possible to design sensors with high
      sensitivity. To demonstrate the advantages of APCNs as matrixes, different
      prototypes of sensors were prepared, e.g., one to determine gaseous chlorine
      based on its reaction with immobilized o-tolidine and another to determine
      vaporous acids based on immobilized bromophenol blue dianions. As a breakthrough
      in biochemical sensing, we are also able to present an easily producible,
      optically transparent biochemical sensor to determine peroxides in nonpolar
      organic media-based on coimmobilized horseradish peroxidase and 2,2'-azino-bis(3
      ethylbenzothiazoline-6-sulfonate).

PMID- 16970312
TI  - Single-walled carbon nanotubes used as stationary phase in GC.
AB  - Single-walled carbon nanotubes (SWNTs) have high surface area, high adsorption
      ability, and nanoscale interactions. In this study, capillary columns including
      SWNTs, ionic liquid (IL), and IL + SWNTs for GC were prepared. The separation
      results showed that SWNTs possessed a wide selectivity toward alkanes, alcohols,
      aromatic compounds, and ketones, and a SWNT capillary column was a very useful GC
      column for the separation of gas samples. Coating the IL stationary phase on the
      SWNT capillary column, the SWNTs were able to improve chromatographic
      characteristic of ionic liquid. Comparing the IL coated on three graphite carbon
      black capillary columns, which were prepared by dynamic coating, static coating,
      and chemical bonding the Carbopack C with on SWNTs capillary column, the capacity
      factors were much higher on the SWNT column. The SEM showed that SWNTs could be
      bonded to the inner surface of capillary tubing, and most of them were linked end
      to-end to form a layer of network structure of skeletons resulting in a high
      surface area, which increased the interactions between stationary phase and
      analytes. This is the first single-wall carbon nanotubes bonded to the fused
      silica capillary tubing. In the first approach, SWNTs assist ionic liquid with
      enhanced chromatographic characteristic in GC. This work indicates that SWNTs
      make it possible to extend the application range on the newly prepared
      chromatographic stationary phases for GC.

PMID- 16970313
TI  - Tandem parallel fragmentation of peptides for mass spectrometry.
AB  - Parallel fragmentations of peptides in the source region and in the collision
      cell of tandem mass spectrometers are sequentially combined to develop parallel
      collision-induced-dissociation mass spectrometry (p2CID MS). Compared to MS/MS
      spectra, the p2CID mass spectra show increased signal intensities (2-400-fold)
      and number of sequence ions. This improvement is attributed to the fact that
      p2CID MS virtually samples all the ions generated by electrospray ionization,
      including intact and fragment ions of different charge states from a peptide. We
      implement the method using a quadrupole time-of-flight tandem mass spectrometer.
      The instrument is operated in TOF-MS mode that allows the ions from source region
      broadband-passing the first mass analyzer to enter the collision cell. Cone
      voltage and collision energy are investigated to optimize the outcome of the two
      parallel CID processes. In the in-source parallel CID, elevated cone voltage
      produces singly charged intact peptide ions and large fragment ions, as well as
      decreases the charge-state distribution of peptide ions mainly to double and
      single charges. The in-collision-cell parallel CID is optimized to dissociate the
      ions from the source region to produce small and medium fragment ions. The method
      of p2CID MS is especially useful for sequencing of large peptides with labile
      amide bonds and peptides with C-terminal arginine. It has unique potential for de
      novo sequencing of peptides and proteome analysis, especially for affinity
      enriched subproteomes.

PMID- 16970314
TI  - Ionizable isotopic labeling reagent for relative quantification of amine
      metabolites by mass spectrometry.
AB  - A powerful approach to relative quantification by mass spectrometry is to employ
      labeling reagents that target specific functional groups in molecules of
      interest. A quantitative comparison of two or more samples may be readily
      accomplished by using a chemically identical but isotopically distinct labeling
      reagent for each sample. The samples may then be combined, subjected to
      purification steps, and mass analyzed. Comparison of the signal intensities
      obtained from the isotopically labeled variants of the target analyte(s) provides
      quantitative information on their relative concentrations in the sample. In this
      report, we describe the synthesis and use of heavy and light isotopic forms of
      methyl acetimidate for the relative quantification of amine-containing species.
      The principal advantages of methyl acetimidate as a labeling reagent are that the
      reaction product is positively charged and hydrophobicity is increased, both of
      which enhance electrospray ionization efficiency and increase detection
      sensitivity. The quantitative nature of the analysis was demonstrated in model
      metabolomics experiments in which heavy and light labeled Arabidopsis extracts
      were combined in different ratios. Finally, the labeling strategy was employed to
      determine differences in the amounts of amine-containing metabolites for
      Arabidopsis seeds germinated under two different conditions.

PMID- 16970315
TI  - Microfluidic sequential injection analysis in a short capillary.
AB  - An automated microfluidic sequential injection analysis system that efficiently
      manipulates sample and reagent solutions in the nanoliter range in approximately
      10 s per analytical cycle is described. The system consisted of a 6-cm-long,
      typically 75-microm i.d., fused-silica capillary (which functioned as a sampling
      probe and reactor as well as a flow-through detection cell), a horizontally
      oriented waste reservoir that provided liquid level differences for inducing
      gravity-driven flows, an autosampling device holding samples and reagents with
      horizontally fixed slotted microvials, and a laser-induced fluorescence detection
      system. Sample and reagent zones were sequentially introduced via gravity-driven
      flow by scanning the capillary tip (functioning as the sampling probe) through
      the vial slots, while vials containing sample, reagent, and carrier were
      sequentially rotated to the probe by programmed movement of the vial holders.
      Sequentially injected nanoliter zones were rapidly mixed by convection and
      diffusion within the carrier flow, demonstrating a behavior that conformed well
      to the Taylor dispersion model, and zone penetration effects were characterized
      and optimized under Taylor's dispersion theory guidelines. For the determination
      of fluorescein, a high throughput of 400 h(-1) was achieved, rapidly producing
      calibration curves (five points) within 45 s. Owing to its adaptability to the
      Taylor's dispersion model, the system was used also for measuring diffusion
      coefficients of fluorescent species. Potentials for using the system in enzyme
      inhibition assays were demonstrated by a reaction involving the conversion of
      fluorescein digalactoside to fluorescent hydrolysates via beta-galactosidase and
      the inhibition of beta-galactosidase by diethylenetriaminepentaacetic acid.

PMID- 16970316
TI  - Screening of glycosylation patterns in serum using natural glycoprotein
      microarrays and multi-lectin fluorescence detection.
AB  - Protein glycosylation has been implicated in key biological processes including
      immunological recognition, cellular adhesion, protein folding, and signaling as
      well as disease progression. Although several methods are available to assess
      glycosylation of protein structures, none of them is able to screen complex
      biological samples at a global as well as an individual scale. A novel strategy
      presented here uses an all-liquid phase enrichment and prefractionation
      methodology coupled to glycoprotein microarray technology using a multiple lectin
      based, biotin-streptavidin detection scheme. Selective detection of glycan
      structures was made possible by employing multiple lectins to screen glycoprotein
      standards as well as serum samples from normal subjects or patients with chronic
      pancreatitis or pancreatic cancer. Interestingly, in some instances, a greater
      degree of glycosylation was seen in proteins that were underexpressed based on
      the reversed-phase chromatogram alone. Studies with standard proteins established
      the limits of detection to be in the 2.5-5-fmol range. Studies on serum samples
      showed differences in glycosylation patterns, particularly with respect to
      sialylation, mannosylation, and fucosylation, in normal, pancreatitis, and cancer
      sera. By coupling glycoprotein enrichment and fractionation with a microarray
      platform, we have shown that naturally occurring glycoproteins from human serum
      can be screened and characterized for different glycan structures, thereby
      allowing one to do comparative studies that monitor individual glycosylation
      changes within a glycoproteome representing different biological states. This
      approach may be useful to identify potential biomarkers in cancer.

PMID- 16970317
TI  - Quantification of N-(deoxyguanosin-8-yl)-4-aminobiphenyl adducts in human
      lymphoblastoid TK6 cells dosed with N-hydroxy-4-acetylaminobiphenyl and their
      relationship to mutation, toxicity, and gene expression profiling.
AB  - Gene expression profiles that are anchored to phenotypic endpoints may lead to
      the identification of signatures that predict mutagenicity or carcinogenicity.
      The study presented here describes the analysis of DNA adducts in the human TK6
      lymphoblastoid cell line after exposure to N-hydroxy-4-aminobiphenyl, a mutagenic
      metabolite of 4-aminobiphenyl. A validated nano-LC microelectrospray mass
      spectrometry assay is reported for the detection and quantification of N
      (deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP), the principal DNA adduct of 4
      aminobiphenyl. Limits of quantification, based on a signal-to-noise ratio of
      10:1, are determined to correspond to approximately 27 fg of dG-C8-ABP injected
      on-column. The assay has been used to measure the steady-state levels of the
      adduct in the human TK6 lymphoblastoid cell line as a function of dose (0.5, 1.0,
      and 10.0 microM) and time (2, 6, and 27 h) after exposure to N-hydroxy-4
      aminobiphenyl. The levels of dG-C8-ABP adducts in the cells, ranging from 18 to
      500 adducts in 10(9) nucleotides, were then correlated to cell toxicity, induced
      mutation at the TK (thymidine kinase) and HPRT loci, and gene expression
      profiling through microarray analysis. Cell cultures were evaluated for toxicity
      by growth curve extrapolation, mutation assays were performed on the HPRT and TK
      loci, and gene expression profiles were generated by analyses using microarray
      technology. In the mutation assay analysis, as the toxicant concentration
      increased, there was an increase in mutation fraction, indicating a direct
      correlation to metabolite dosing level and mutations occurring at these two loci.
      Statistical analysis of the gene expression data determined that a total of 2250
      genes exhibited statistically significant changes in expression after treatment
      with N-OH-AABP (P < 0.05). Among the genes identified, 2245 were up-regulated,
      whereas 5 genes that had functions in cell survival and cell growth and, hence,
      could be indicators of toxicity, were down-regulated relative to controls. The
      results demonstrate the value of anchoring gene expression patterns to phenotypic
      markers, such as DNA adduct levels, toxicity, and mutagenicity.

PMID- 16970318
TI  - Microfluidic and optical systems for the on-demand generation and manipulation of
      single femtoliter-volume aqueous droplets.
AB  - This paper describes a fluidic and optical platform for the generation and
      manipulation of single femtoliter-volume aqueous droplets. Individual droplets
      were generated on-demand using a microfluidic chamber that confers environmental
      flow stability. Optical vortex traps were implemented to manipulate and transport
      the generated droplets, which have a lower refractive index than the immiscible
      medium in which the droplets are immersed and thus cannot be trapped using
      conventional optical tweezers. We also demonstrated the ability to shrink and
      increase the refractive index of the generated droplet, thereby permitting its
      facile fusion with another droplet using an optical tweezer. To illustrate the
      versatility of this platform, we have performed both fast (<1 s) and slow (>1 h)
      chemical reactions in these femtoliter-volume aqueous droplets.

PMID- 16970319
TI  - Establishment of an extraction method for the recovery of tattoo pigments from
      human skin using HPLC diode array detector technology.
AB  - Tattooing is a widespread process of puncturing pigments into skin, whereas the
      resulting concentration inside the skin remains unknown. Many tattoo colorants
      are organic pigments, such as azo pigments, manufactured for other uses. To
      remove tattoos from skin, laser pulses at very high intensities are applied to
      the skin to destroy the tattoo pigments. Recent investigations have shown that
      several azo compounds are cleaved by laser light leading to potentially toxic or
      carcinogenic compounds. To assess the risk of tattooing and laser treatment of
      tattoos, the concentration of the pigments and their decomposition products in
      the skin must be determined. Therefore, an extraction method was established to
      determine the concentration of tattoo pigments and decomposition products
      quantitatively. The extraction of two widely used azo compounds, Pigment Red 22
      and Pigment Red 9, and their laser-induced decomposition products, 2-methyl-5
      nitroaniline, 4-nitrotoluene, 2,5-dichloraniline, and 1,4-dichlorobenzene, was
      accomplished using recovery experiments and HPLC-DAD technology. Despite the poor
      solubility of the pigments, a nearly complete recovery from aqueous suspension (>
      92%) or lysed skin (> 94%) was achieved. The decomposition products were
      extracted from aqueous suspension or skin showing a recovery of up to 100%,
      except for the very volatile 1,4-DCB.

PMID- 16970320
TI  - Direct molecular analysis of whole-body animal tissue sections by imaging MALDI
      mass spectrometry.
AB  - Imaging mass spectrometry (IMS) that utilizes matrix-assisted laser
      desorption/ionization (MALDI) technology can provide a molecular ex vivo view of
      resected organs or whole-body sections from an animal, making possible the label
      free tracking of both endogenous and exogenous compounds with spatial resolution
      and molecular specificity. Drug distribution and, for the first time, individual
      metabolite distributions within whole-body tissue sections can be detected
      simultaneously at various time points following drug administration. IMS analysis
      of tissues from 8 mg/kg olanzapine dosed rats revealed temporal distribution of
      the drug and metabolites that correlate to previous quantitative whole-body
      autoradiography studies. Whole-body MALDI IMS is further extended to detecting
      proteins from organs present in a whole-body sagittal tissue section. This
      technology will significantly help advance the analysis of novel therapeutics and
      may provide deeper insight into therapeutic and toxicological processes,
      revealing at the molecular level the cause of efficacy or side effects often
      associated with drug administration.

PMID- 16970321
TI  - Probing topography and tailing for commercial stationary phases using AFM, FT-IR,
      and HPLC.
AB  - Atomic force microscopy was used to study surface characteristics of three
      chromatographic silica products: Agilent Zorbax SB300, Waters Symmetry 300, and
      Merck Chromolith. Each is modified with a monomeric C18 monolayer. Both
      topographic and adhesive force measurements were made for each product.
      Topographical images revealed that all three materials are as smooth as glass on
      the scale of 100 nm and below. Adhesive forces for all three materials were much
      lower and much more uniform than for chemically modified fused silica. FT-IR
      spectra for all three materials showed a low abundance of isolated silanols, thus
      explaining the low adhesion. Chromatograms of a cationic dye, 1,1'-didodecyl
      3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI), ranging in concentration
      from 1 to 300 microM were obtained for each column. All three materials exhibited
      classic nonlinear tailing; the Zorbax exhibited fronting as well. Chromatographic
      simulations were performed for the Symmetry and Chromolith products to determine
      the number of strong adsorption sites. The AFM, FT-IR, and HPLC were all
      consistent in indicating that the Chromolith material had half as many strong
      adsorption sites as the Symmetry material. The Zorbax material exhibited a number
      of isolated silanols that was comparable to the other materials, yet its adhesive
      force suggested a less adsorptive material, and its chromatographic performance
      suggested a more adsorptive material. Its topography is discussed as a possible
      reason for its anomalous chromatographic behavior.

PMID- 16970322
TI  - Multiple label-free detection of antigen-antibody reaction using localized
      surface plasmon resonance-based core-shell structured nanoparticle layer
      nanochip.
AB  - In this research, a localized surface plasmon resonance (LSPR)-based bioanalysis
      method for developing multiarray optical nanochip suitable for screening
      bimolecular interactions is described. LSPR-based label-free monitoring enables
      to solve the problems of conventional methods that require large sample volumes
      and time-consuming labeling procedures. We developed a multiarray LSPR-based
      nanochip for the label-free detection of proteins. The multiarray format was
      constructed by a core-shell-structured nanoparticle layer, which provided 300
      nanospots on the sensing surface. Antibodies were immobilized onto the nanospots
      using their interaction with Protein A. The concentrations of antigens were
      determined from the peak absorption intensity of the LSPR spectra. We
      demonstrated the capability of the array measurement using immunoglobulins (IgA,
      IgD, IgG, IgM), C-reactive protein, and fibrinogen. The detection limit of our
      label-free method was 100 pg/mL. Our nanochip is readily transferable to monitor
      the interactions of other biomolecules, such as whole cells or receptors, with a
      massively parallel detection capability in a highly miniaturized package. We
      anticipate that the direct label-free optical immunoassay of proteins reported
      here will revolutionize clinical diagnosis and accelerate the development of hand
      held and user-friendly point-of-care devices.

PMID- 16970323
TI  - Multiplex measurement of seven tumor markers using an electrochemical protein
      chip.
AB  - An electrochemical immunosensor for performing multianalyte measurements of tumor
      markers is described. The sensor consisted of an array of immunosensing
      electrodes fabricated on a glass substrate. Each electrode contained a different
      immobilized antigen and was capable of measuring a specific tumor marker using
      electrochemical enzyme-based competitive immunoassay. Using this arrangement,
      multiple analytes could be measured simultaneously by performing the technical
      operations for a single assay. The biosensor was used to measure the
      concentrations of seven important tumor markers: AFP, ferritin, CEA, hCG-beta, CA
      15-3, CA 125, and CA 19-9. The sensor had excellent precision and accuracy and
      was comparable in performance to single-analyte ELISAs (1.9-8.1% interassay CV;
      <2 ng/mL (or units/mL) detection limit for most analytes). Multianalyte assays
      provide significant advantages over single-analyte tests in terms of cost per
      test, labor, test throughput, and convenience. We anticipate that chip-based
      sensors, as described herein, will be suitable for the mass production of
      economical, miniaturized lab-on-a-chip devices that will have applications in a
      wide range of clinical, environmental, and biodefense applications.

PMID- 16970324
TI  - Signaling aptamers created using fluorescent nucleotide analogues.
AB  - A new approach to creating fluorescent signaling aptamers using fluorescent
      nucleotide analogues is presented. The fluorescence quantum yield of nucleotide
      analogues such as 2-aminopurine strongly depends on base stacking interactions
      when incorporated into double or single stranded DNA. This property is used to
      generate a binding-specific fluorescence signal. Aptamers for human alpha
      thrombin, immunoglobulin E, and platelet-derived growth factor B were modified
      with fluorescent nucleotide analogues in positions that undergo conformational
      changes. The resulting signaling aptamers show a specific, binding-induced
      increase in the fluorescence signal of up to 30-fold. Conformation-changing
      positions in these aptamers were identified by screening a set of modified
      aptamer sequences that each included a fluorescent nucleotide analogue at a
      different position. The positions for these modifications were estimated by
      modeling the aptamer secondary structure. It is likely that this approach to
      producing fluorescent signaling aptamers is of general use for protein-binding
      aptamers because of their "induced fit" binding mechanism.

PMID- 16970325
TI  - Quantitative screening of single copies of human papilloma viral DNA without
      amplification.
AB  - We describe a novel quantitative viral screening method based on single-molecule
      detection that does not require amplification. DNA of human papilloma virus
      (HPV), the major etiological agent of cervical cancer, served as the screening
      target in this study. Eight 100-nucleotide single-stranded DNA probes were
      designed complementary to the E6-E7 gene of HPV-16 DNA. The probes were
      covalently stained with Alexa Fluor 532 and hybridized to the target in solution.
      The individual hybridized molecules were imaged with an intensified charge
      coupled device (ICCD) in two ways. In the single-color mode, target molecules
      were detected via fluorescence from hybridized probes only. This system could
      detect HPV-16 DNA in the presence of human genomic DNA down to 0.7 copy/cell and
      had a linear dynamic range of over 6 orders of magnitude. In the dual-color mode,
      we employed fluorescence resonance energy transfer and added YOYO-3 dye as the
      acceptor. The two colors from Alexa Fluor 532 and YOYO-3 were dispersed by a
      transmission grating located in front of the ICCD. With this reinforced criterion
      for identifying the hybridized molecules, zero false-positive count was achieved.
      We also showed that DNA extracts from Pap test specimens did not interfere with
      the measurements.

PMID- 16970326
TI  - Distinguishing monosaccharide stereo- and structural isomers with TOF-SIMS and
      multivariate statistical analysis.
AB  - Time-of-flight secondary ion mass spectrometry (TOF-SIMS) is utilized to examine
      the mass spectra and fragmentation patterns of seven isomeric monosaccharides.
      Multivariate statistical analysis techniques, including principal component
      analysis (PCA), allow discrimination of the extremely similar mass spectra of
      stereoisomers. Furthermore, PCA identifies those fragment peaks that vary
      significantly between spectra. Heavy isotope studies confirm that these peaks are
      indeed sugar fragments, allow identification of the fragments, and provide clues
      to the fragmentation pathways. Excellent reproducibility is shown by multiple
      experiments performed over time and on separate samples. This study demonstrates
      the combined selectivity and discrimination power of TOF-SIMS and PCA and
      suggests new applications of the technique including differentiation of subtle
      chemical changes in biological samples that may provide insights into cellular
      processes, disease progress, and disease diagnosis.

PMID- 16970327
TI  - Surface plasmon resonance imaging measurements of antibody arrays for the
      multiplexed detection of low molecular weight protein biomarkers.
AB  - This paper describes a simple methodology for the creation of high-density
      multiplexed antibody arrays on gold surfaces that can be used to detect low
      molecular weight protein biomarkers with surface plasmon resonance imaging
      (SPRI). A one-step carbonyldiimidazole (CDI) surface reaction was utilized to
      attach antibodies onto alkanethiol-modified gold surfaces and characterized with
      polarization modulation FT-IR reflection absorption spectroscopy. The CDI
      chemistry was then employed to create an antibody microarray with array element
      sizes varying from 750 microm down to 200 microm. As a demonstration, a three
      component antibody array was employed to detect two clinically important protein
      biomarkers, beta2-microglobulin (11.8 kDa) and cystatin C (13.4 kDa). SPRI
      measurements could simultaneously detect both of these small unlabeled proteins
      with no cross talk at solution concentrations from 300 nM down to 1 nM. In
      addition, the adsorption strengths of these biomarkers onto an antibody array
      were measured with SPRI and compared to those obtained from the kinetic analysis
      of single-channel angle shift SPR measurements.

PMID- 16970328
TI  - Dynamic isoelectric focusing for proteomics.
AB  - Dynamic isoelectric focusing is a new technique that is related to capillary
      isoelectric focusing but uses additional high-voltage power supplies to provide
      control over the shape of the electric field within the capillary. Manipulation
      of the electric field changes the pH gradient, enabling both the location and
      width of the focused protein bands to be controlled. The proteins can be migrated
      to a designated sampling point while remaining focused, where they can be
      collected for further analysis. This ability to collect and isolate the protein
      bands while maintaining a high peak capacity demonstrates that dynamic
      isoelectric focusing has great potential as a first dimension in a
      multidimensional separation system. Dynamic isoelectric focusing can achieve a
      peak capacity of over 1000, as shown by both mass spectrometry analysis and
      direct imaging.

PMID- 16970330
TI  - Kinetics of electron-transfer reactions at nanoelectrodes.
AB  - The kinetics of several fast heterogeneous electron-transfer reactions were
      investigated by steady-state voltammetry at nanoelectrodes and scanning
      electrochemical microscopy (SECM). The disk-type, polished Pt nanoelectrodes (3.7
      400-nm radius) were characterized by a combination of voltammetry, scanning
      electron microscopy, and SECM. A number of experimental curves were obtained at
      the same nanoelectrode to attain the accuracy and reproducibility similar to
      those reported previously for micrometer-sized probes. A new analytical
      approximation was developed and used for analysis of steady-state tip
      voltammograms. The self-consistent kinetic parameter values with the uncertainty
      margin of approximately 10% were obtained for electrodes of different radii and
      for a wide range of the SECM tip/substrate separation distances. The determined
      standard rate constants are compared to those previously measured at the
      electrodes of different dimensions, and the correlation between the heterogeneous
      and self-exchange rate constants is discussed.

PMID- 16970329
TI  - Experimental study on band dispersion in channels structured with micropillars.
AB  - The band dispersion in channels with an orderly pillar structure with a pressure
      driven liquid flow was determined. Several channels with different geometries
      were etched in a silicon wafer and enclosed by a glass wafer. The microchannels
      obtained had the same depth, pillar disposition, and overall porosity, but
      different pillar diameters and channel widths. The broadening of narrow bands of
      a fluorescent sample solution flowing through the channels was measured using a
      fluorescence microscope. It was shown that the peak dispersion occurring in the
      channels can be much lower than in conventional packed columns, as a consequence
      of the higher degree of order of the solid structure. Reduced plate heights of
      approximately 0.2 could be obtained for (nonretained) bands. No correlation was
      found between the aspect ratio (the ratio of the channel width and the pillar
      diameter) and band dispersion. The geometrical construction of the sidewall
      region was shown to play a critical role for channel performance. A good
      agreement was found with predictions for the optimal sidewall geometry obtained
      previously with simulation studies.

PMID- 16970331
TI  - Alternating current impedance imaging of high-resistance membrane pores using a
      scanning electrochemical microscope. Application of membrane electrical shunts to
      increase measurement sensitivity and image contrast.
AB  - Whether an individual pore in a porous membrane can be imaged using scanning
      electrochemical microscopy (SECM), operated in ac impedance mode, is determined
      by the magnitude of the change in the total impedance of the imaging system as
      the SECM tip is scanned over the pore. In instances when the SECM tip resistance
      is small relative to the internal pore resistance, the total impedance changes by
      a negligible amount, rendering the pore invisible during impedance imaging. A
      simple solution to this problem is to introduce a low-impedance electrical shunt
      (i.e., a salt bridge) across the membrane. This principle is demonstrated by
      imaging polycarbonate membranes (6-12-microm thickness) containing between 1 and
      2000 conical-shaped pores (60-nm- and 2.5-microm-diameter openings) using an
      approximately 1-microm-radius Pt tip. Theory and experiments show that image
      contrast (the change in ac current measured as the probe is scanned over the
      pore) is inversely proportional to the total resistance of the membrane and can
      be increased by a factor of approximately 50x by introducing a low-resistance
      electrical shunt across the membrane. Remarkably, SECM images of membranes
      containing a single high-resistance (approximately 1 G Omega) pore can only be
      imaged by short-circuiting the membrane. Image contrast also becomes independent
      of membrane resistance when an electrical shunt is used, allowing for more
      quantitative comparisons of the features in ac impedance images of different
      membranes.

PMID- 16970332
TI  - Determination of triclosan as its pentafluorobenzoyl ester in human plasma and
      milk using electron capture negative ionization mass spectrometry.
AB  - A sensitive method for the determination of triclosan in plasma and milk is
      presented. Following hydrolysis of possible conjugates, triclosan is extracted
      with n-hexane/acetone, partitioned into alcoholic potassium hydroxide, and
      converted into its pentafluorobenzoyl ester. After sulfuric acid cleanup, sample
      extracts are analyzed by gas chromatography/electron capture negative ionization
      mass spectrometry. The limit of quantification was 0.009 ng/g for a 5-g plasma
      sample and 0.018 ng/g for a 3-g milk sample. The coefficient of variation for the
      method was 6%. The method was tested on more than 70 human plasma and milk
      samples, of which all plasma samples and more than half of the milk samples were
      above the limit of quantification. The presented method has lowered the limit of
      quantification for triclosan in human matrixes significantly as compared to
      previous methods and makes possible the analysis of triclosan in humans under
      normal exposure conditions.

PMID- 16970333
TI  - Passive sampling of airborne peroxyacetic acid.
AB  - The first passive sampling device for the determination of airborne peroxyacetic
      acid (PAA) is presented. 2-([3-{2-[4-Amino-2-(methylsulfanyl)phenyl]-1
      diazenyl}phenyl]sulfonyl)-1-ethanol (ADS) is used to impregnate glass fiber
      filters, and the reagent is oxidized by PAA to the corresponding sulfoxide ADSO.
      After elution of the filters, ADS and ADSO are separated by reversed-phase HPLC
      and detected by UV/visible absorbance. Limit of detection is 30 ppb, limit of
      quantification is 90 ppb (for 30 min sampling), and the linear range comprises 2
      orders of magnitude. Thorough investigations were carried out with respect to the
      selectivity of the method toward hydrogen peroxide, and air samples were analyzed
      successfully after disinfection of a laboratory area.

PMID- 16970334
TI  - Isolation and identification of sialylated glycopeptides from bovine alpha1-acid
      glycoprotein by off-line capillary electrophoresis MALDI-TOF mass spectrometry.
AB  - Sialylated glycopeptides contained in liquid chromatographic fractions of bovine
      alpha1-glycoprotein tryptic digests were isolated from asialo peptides using
      capillary electrophoresis (CE). CE effluents were deposited directly onto a
      metallic target and analyzed using matrix-assisted laser desorption/ionization
      (MALDI) mass spectrometry. This method allowed the characterization of four N
      glycosylation sites in the glycoprotein, and each site was observed as a set of
      sialylated peptide glycoforms. Tandem mass spectrometry was used to confirm
      peptide sequences and glycan content in glycoforms. The CE method developed for
      this study resulted in a very clear separation of the sialylated from the asialo
      content of glycoprotein digests and proved very useful in the determination of
      the nature and location of sialylated glycans along the protein chain. This
      article is the first report describing the use of on-target CE fraction
      collection using a MALDI removable sample concentrator.

PMID- 16970335
TI  - Electron photodetachment dissociation of DNA polyanions in a quadrupole ion trap
      mass spectrometer.
AB  - We hereby explore the effects of irradiating DNA polyanions stored in a
      quadrupole ion trap mass spectrometer with an optical parametric oscillator laser
      between 250 and 285 nm. We studied DNA 6-20-mer single strands and 12-base pair
      double strands. In all cases, laser irradiation causes electron detachment from
      the multiply charged DNA anions. Electron photodetachment efficiency directly
      depends on the number of guanines in the strand, and maximum efficiency is
      observed between 260 and 275 nm. Subsequent collision-induced dissociation (CID)
      of the radical anions produced by electron photodetachment results in extensive
      fragmentation. In addition to neutral losses, a large number of fragments from
      the w, d, a*, and z* ion series are obtained, contrasting with the w and (a-base)
      ion series observed in regular CID. The major advantage of this technique, coined
      electron photodetachment dissociation (EPD) is the absence of internal fragments,
      combined with good sequence coverage. EPD is therefore a highly promising
      approach for de novo sequencing of oligonucleotides. EPD of nucleic acids is also
      expected to give specific radical-induced strand cleavages, with conservation of
      other fragile bonds, including noncovalent bonds. In effect, preliminary results
      on a DNA hairpin and on double strands suggest that EPD could also be used to
      probe intra- and intermolecular interactions in nucleic acids.

PMID- 16970336
TI  - Simultaneous quantitative analysis of metabolites using ion-pair liquid
      chromatography-electrospray ionization mass spectrometry.
AB  - We have developed an analytical method, consisting of ion-pair liquid
      chromatography coupled to electrospray ionization mass spectrometry (IP-LC-ESI
      MS), for the simultaneous quantitative analysis of several key classes of polar
      metabolites, like nucleotides, coenzyme A esters, sugar nucleotides, and sugar
      bisphosphates. The use of the ion-pair agent hexylamine and optimization of the
      pH of the mobile phases were critical parameters in obtaining good retention and
      peak shapes of many of the above-mentioned polar and acidic metabolites that are
      impossible to analyze using standard reversed-phase LC/MS. Optimum conditions
      were found when using a gradient from 5 mM hexylamine in water (pH 6.3) to 90%
      methanol/10% 10 mM ammonium acetate (pH 8.5). The IP-LC-ESI-MS method was
      extensively validated by determining the linearity (R2 > 0.995), sensitivity
      (limit of detection 0.1-1 ng), repeatability, and reproducibility (relative
      standard deviation <10%). The IP-LC-ESI-MS method was shown to be a useful tool
      for microbial metabolomics, i.e., the comprehensive quantitative analysis of
      metabolites in extracts of microorganisms, and for the determination of the
      energy charge, i.e., the cellular energy status, as an overall quality measure
      for the sample workup and analytical protocols.

PMID- 16970337
TI  - Optimization and validation of a quantitative capillary electrophoresis sodium
      dodecyl sulfate method for quality control and stability monitoring of monoclonal
      antibodies.
AB  - In previous work, a capillary electrophoresis sodium dodecyl sulfate (CE-SDS)
      method using precolumn labeling and laser-induced fluorescence (LIF) detection
      was developed at Genentech Inc. as part of the control system for the quality
      control release of a recombinant monoclonal antibody (rMAb) (Hunt, G.; Nashabeh,
      W. Anal. Chem. 1999, 71, 2390-2397.). In the current work, a generic and
      quantitative CE-SDS assay with LIF detection of rMAbs with improved accuracy and
      precision is described. The implementation of an alkylating step with
      iodoacetamide and optimization of the incubation temperature and time, in the
      presence of SDS, greatly decrease any thermally induced fragmentation of
      nonreduced labeled rMAb samples. In addition, a quantitative study of the effects
      of sample buffer pH on rMAb fragmentation is also presented. Furthermore, the
      performance of alternative CE-SDS polymer solutions and instrumentation for
      quantitative analysis of rMAbs is shown in this article. The validation of this
      method, under the guidelines of the International Committee on Harmonization
      (ICH), demonstrates that the assay quantitatively determines the consistency of
      rMAb manufacture as it relates to size heterogeneity and product purity.

PMID- 16970338
TI  - Use of thermal desorption mass spectrometry for the detection of free acid
      impurities in pharmaceutical products.
AB  - A method utilizing thermal desorption mass spectrometry (TDMS) for the detection
      and quantitation of free acid forms in pharmaceutical drug products formulated as
      salts is presented. Selective detection of neutral drug forms is possible because
      the volatility of a drug present in its free acid form is typically much higher
      than that of its corresponding salt forms, which have negligible volatility even
      at high temperatures. Tandem mass spectrometric detection allows selective
      quantitation of the desired free acid drug forms without significant
      interferences from formulation excipients. The application of the TDMS approach
      is demonstrated for a sodium salt of a representative, carboxylated drug
      molecule. Excellent sensitivity, specificity, and adequate linearity of detector
      signal as a function of micrograms of free acid added were demonstrated in the
      presence of the sodium salt of the drug and formulation excipients. The
      sensitivity of the method was demonstrated at free acid levels of 0.6% w/w (6
      microg absolute mass). Tablet samples were analyzed by thermal desorption EI
      MS/MS with reference to external standards using a commercially available
      quadrupole ion trap mass spectrometer. The relative drug form stabilities in
      three different tablet formulations were differentiated using this method; the
      salt-to-free acid form conversion ranged between less than the limit of detection
      to near complete conversion during the stability study.

PMID- 16970339
TI  - Antibody microarray detection of Escherichia coli O157:H7: Quantification, assay
      limitations, and capture efficiency.
AB  - A sandwich fluorescent immunoassay in a microarray format was used to capture and
      detect E. coli O157:H7. Here, we explored quantitative aspects, limitations, and
      capture efficiency of the assay. When biotinylated capture antibodies were used,
      the signal generated was higher (over 5-fold higher with some cell
      concentrations) compared to biotinylated protein G-bound capture antibodies. By
      adjusting the concentration of reporter antibody, a linear fluorescent response
      was observed from approximately 3.0 x 10(6) to approximately 9.0 x 10(7)
      cells/mL, and this was in agreement with the number of captured bacteria as
      determined by fluorescence microscopy. Capture efficiency calculations revealed
      that, as the number of bacteria presented for capture decreased, capture
      efficiency increased to near 35%. Optimization experiments, with several
      combinations of capture and reporter antibodies, demonstrated that the amount of
      bacteria available for capture (10(6) versus 10(8) cells/mL) affected the optimal
      combination. The findings presented here indicate that antibody microarrays, when
      used in sandwich assay format, may be effectively used to capture and detect E.
      coli O157:H7.

PMID- 16970340
TI  - On-line enhancement technique for the analysis of nucleotides using capillary
      zone electrophoresis/mass spectrometry.
AB  - A new on-line capillary zone electrophoresis/mass spectrometry (CZE/MS), constant
      pressure-assisted electrokinetic injection (PAEKI), for the analysis of
      negatively charged nucleotides is reported. PAEKI uses an applied pressure to
      counterbalance the reverse electroosmotic flow in the capillary column during
      sample injection, while taking advantage of the field amplification in the sample
      medium. At balance, the running buffer in the column is stationary, permitting
      potentially unlimited injection time, and hence unlimited sample enrichment
      power. The ability of PAEKI to maintain a narrow sample zone over a long
      injection time seems to be a result of the formation of a high ion concentration
      band at the boundary of the two media due to rapid deceleration of the migrating
      ions at the boundary. The injected amount of analytes proved to be linearly
      proportional to both the field amplification factor, which is expressed as the
      ratio of resistivities of sample medium to running buffer, and the injection
      time, which extended up to 1200 s in CZE/MS and 3600 s in CZE/UV. For a 300-s on
      line PAEKI injection in CZE/MS, 3 orders of magnitude sample enhancement (5000
      fold enrichment) could be observed for the four single nucleotides without
      compromising separation efficiency and peak shape, and an achievement of
      detection limits between 0.04 and 0.07 ng/mL. With appropriate sample cleanup,
      PAEKI can be used in the analysis of single nucleotides in enzyme-digested DNA.

PMID- 16970342
TI  - Biomolecular sensing using near-null single wavelength arrayed imaging
      reflectometry.
AB  - We use reflectivity changes at an interface functionalized with molecular probes
      to detect label-free biomolecular binding. Attachment of the target molecules to
      the surface alters the effective thickness of an antireflective coating formed by
      thermal oxidation of a silicon wafer to remove destructive interference of the
      reflected waves. The thermal oxide thickness is adjusted for precise interference
      using electrostatic layer-by-layer self-assembly of polyelectrolytes to which the
      molecular probes can be bound covalently. Reflectivity increases of over a factor
      of 100 are observed for binding of 2.5 nm of streptavidin to biotinylated
      polyelectrolytes, considerably more sensitive than surface plasmon resonance
      detection. Theoretical modeling is in agreement with the experimentally observed
      reflectivity increases and suggests the sensitivity is at present limited by the
      roughness of the oxide.

PMID- 16970341
TI  - Method for quantitative proteomics research by using metal element chelated tags
      coupled with mass spectrometry.
AB  - The mass spectrometry-based methods with a stable isotope as the internal
      standard in quantitative proteomics have been developed quickly in recent years.
      But the use of some stable isotope reagents is limited by the relative high price
      and synthetic difficulties. We have developed a new method for quantitative
      proteomics research by using metal element chelated tags (MECT) coupled with mass
      spectrometry. The bicyclic anhydride diethylenetriamine-N,N,N',N' ',N' '
      pentaacetic acid (DTPA) is covalently coupled to primary amines of peptides, and
      the ligand is then chelated to the rare earth metals Y and Tb. The tagged
      peptides are mixed and analyzed by LC-ESI-MS/MS. Peptides are quantified by
      measuring the relative signal intensities for the Y and Tb tag pairs in MS, which
      permits the quantitation of the original proteins generating the corresponding
      peptides. The protein is then identified by the corresponding peptide sequence
      from its MS/MS spectrum. The MECT method was evaluated by using standard proteins
      as model sample. The experimental results showed that metal chelate-tagged
      peptides chromatographically coeluted successfully during the reversed-phase LC
      analysis. The relative quantitation results were accurate for proteins using
      MECT. DTPA modification of the N-terminal of peptides promoted cleaner
      fragmentation (only y-series ions) in mass spectrometry and improved the
      confidence level of protein identification. The MECT strategy provides a simple,
      rapid, and economical alternative to current mass tagging technologies available.

PMID- 16970343
TI  - Development and evaluation of a candidate reference measurement procedure for the
      determination of progesterone in human serum using isotope-dilution liquid
      chromatography/tandem mass spectrometry.
AB  - Progesterone is a steroid hormone that is involved in regulating female
      reproductive processes. Its concentration in blood is measured to determine
      ovarian function. A candidate reference measurement procedure for progesterone in
      human serum involving isotope dilution coupled with liquid chromatography/tandem
      mass spectrometry (LC/MS/MS) has been developed and critically evaluated. The
      progesterone along with its internal standard (progesterone-13C2) was extracted
      from the serum matrix using liquid-liquid extraction prior to reversed-phase
      LC/MS/MS. The accuracy of the measurement was evaluated by a comparison of
      results of this method on a lyophilized human serum reference material for
      progesterone [Certified Reference Material (CRM) 347] with the certified values
      determined by gas chromatography/mass spectrometry (GC/MS) reference methods and
      by a recovery study for the added progesterone. The results of this method for
      progesterone agreed with the certified value within the uncertainty of the
      measurements for the CRM 347. The recovery of the added progesterone ranged from
      100.1 to 100.9%. This method was applied to the determination of progesterone in
      frozen serum samples from three individual female donors with the progesterone
      concentrations ranging from 0.151 to 24.42 ng/g. Excellent reproducibility was
      obtained with within-set coefficients of variation (CVs) ranging from 0.1 to
      1.4%, and between-set CVs ranging from 0.3 to 0.5%. Excellent linearity was also
      obtained with correlation coefficients of all linear regression lines (measured
      intensity ratios vs mass ratios) ranging from 0.9998 to 1.0000. The detection
      limit at a signal-to-noise ratio of approximately 3 was 1.8 pg of progesterone.
      This well-characterized LC/MS/MS method for serum progesterone, which
      demonstrates good accuracy and precision, low susceptibility to interferences,
      and comparability with GC/MS reference methods, qualifies as a reference
      measurement procedure that can be used to provide an accuracy base to which
      routine methods for progesterone can be compared and that will serve as a
      standard of higher order for measurement traceability.

PMID- 16970344
TI  - Detection of palladium by cold atom solution atomic absorption.
AB  - One of the largest obstacles in miniaturizing traditional atomic spectroscopic
      sources is the need for a thermal/electrical source for free atom production. A
      single article in the literature has demonstrated atomic absorption detection of
      Ag, Cu, and Pd in solution at room temperature for atoms in the gas phase, which
      may ultimately permit miniaturization. Unfortunately, several laboratories have
      found that reproducing the phenomenon has been difficult. Without a sound
      fundamental explanation of the processes leading to the signal, one must conclude
      that it can be done, but some unsuspected and unknown design/methodological
      nuances are responsible for only a single reported success. Gas phase atoms could
      exist at room temperature "in solution" if the atoms were trapped in very small
      bubbles. In the current study, submicrometer-sized bubbles were created in a flow
      through cell during the mixing of an alcohol-water solution containing a reducing
      agent with water containing the analyte. A repeatable atomic absorption signal
      was produced. Replacement of ethanol with 1-propanol and use of a surfactant
      increased the signal. Limits of detection of approximately 100 ppb in Pd were
      achieved, and it is estimated that approximately 0.4% of the Pd initially added
      is contained within the bubbles as gaseous atoms. The paper discusses the
      fundamental processes needed to achieve a repeatable signal.

PMID- 16970345
TI  - Verification of exposure to organophosphates: Generic mass spectrometric method
      for detection of human butyrylcholinesterase adducts.
AB  - We present a generic mass spectrometric method to verify exposure to
      organophosphates, based on the chemical conversion of the phosphylated peptides
      obtained after pepsin digestion of human butyrylcholinesterase (HuBuChE) to a
      common precursor peptide. After exposure of plasma to various organophosphates
      (nerve agents, pesticides), HuBuChE was isolated from plasma by procainamide
      affinity-based solid-phase extraction. Upon subsequent pepsin digestion, the
      respective phosphylated nonapeptides could be identified in the digests. After
      treatment of the pepsin digests with Ba(OH)2 in the presence of a nucleophilic
      tag (a thiol or amine), the phosphylated nonapeptides were transformed into a
      common tagged nonapeptide that could be analyzed sensitively by means of LC
      tandem MS. So far, best results were obtained with 2-(3-aminopropylamino)ethanol
      as nucleophilic tag. By applying the presented method, HuBuChE inhibition can now
      be monitored accurately by mass spectrometry, without advance knowledge of the
      structure of the inhibitor.

PMID- 16970346
TI  - Deamidation of -Asn-Gly- sequences during sample preparation for proteomics:
      Consequences for MALDI and HPLC-MALDI analysis.
AB  - We find that peptides containing -Asn-Gly- sequences typically show approximately
      70-80% degree of deamidation after standard overnight (approximately 12 h)
      tryptic digestion at 37 degrees C. This emphasizes the need for more detailed
      information about the deamidation reaction in -Asn-Gly- sequences, in which two
      deamidated species are produced, one containing an aspartic acid (-Asp-Gly-)
      residue and the other containing an isoaspartic acid (-betaAsp-Gly-) residue. For
      the peptide SLNGEWR (54-60 beta-galactosidase, E. coli), all three components of
      the reaction mixture were separated by HPLC on C18 300-A sorbent, with
      trifluoroacetic acid as an ion-pairing modifier. Their intensity ratios suggested
      the elution order -betaAsp-/-Asn-/-Asp-, which was subsequently confirmed by
      MALDI MS and MS/MS analysis. The kinetics of the deamidation was studied in
      detail for the synthetic SLNGEWR parent using RP HPLC with UV detection. The half
      life of this peptide was found to be approximately 8 h under digestion
      conditions. Analysis of a large pool of peptide retention data shows that the 
      betaAsp-/-Asn-/ -Asp- retention order is normally observed under the above
      conditions, especially if the original -NG- sequence is surrounded by hydrophobic
      amino acids. However, changing chromatographic conditions to 100-A pore size
      sorbents, or using formic acid as a modifier, increases the retention time of 
      betaAsp- relative to the -Asn-/-Asp- pair, so the order can sometimes be
      different.

PMID- 16970347
TI  - Quantifying phthalate metabolites in human meconium and semen using automated off
      line solid-phase extraction coupled with on-line SPE and isotope-dilution high
      performance liquid chromatography--tandem mass spectrometry.
AB  - We developed an analytical method using off-line solid-phase extraction (SPE)
      coupled with on-line SPE and isotope-dilution high-performance liquid
      chromatography-tandem mass spectrometry (HPLC-MS/MS) to determine the
      concentrations of phthalate metabolites in human meconium and in semen. First, we
      used off-line SPE to remove interfering proteins and other biomolecules from the
      samples. Then, we preconcentrated the phthalate metabolites in the extract using
      on-line SPE before measuring them by HPLC-MS/MS. For most of the analytes, the
      limits of detection ranged between 0.2 and 0.7 ng/g for meconium and between 0.3
      and 0.7 ng/mL for semen. The recovery after off-line SPE varied for most analytes
      between 65 and 99% at concentrations ranging from 3.0 to 30.0 ng/mL in semen and
      between 67 and 103% at concentrations ranging from 2.0 to 10.0 ng/mL in meconium.
      Precision measured by the relative standard deviation ranged from 3.2 to 19.1%
      for intraday and from 3.9 to 18.6% for interday. We validated this novel approach
      -which is applicable to other biological matrixes, including serum and breast
      milk--on spiked samples and on five meconium samples and one pooled semen sample
      from people with no known occupational exposure to phthalates.

PMID- 16970348
TI  - Direct DNA hybridization at disposable graphite electrodes modified with carbon
      nanotubes.
AB  - The performance of glassy carbon (GCE) and graphite pencil electrodes (PGE)
      modified with multiwalled carbon nanotubes (CNTs) are compared, based on the
      direct electrochemical detection of nucleic acids. This is accomplished by
      monitoring the differential pulse voltammetry changes of the guanine signal. CNT
      modified PGE compares favorably to that of the commonly used CNT-modified GCE
      owing to the intrinsic improved performance of the supporting PGE. The better
      intrinsic characteristics of the PGE are related to its composite structure and
      higher level of porosity compared to GCE. The performance characteristics of the
      direct DNA hybridization on the disposable CNT-modified PGE are studied in terms
      of optimum analytical conditions such as probe concentration, target
      concentration, hybridization time, and selectivity. The new DNA biosensor
      described here has shown some important advantages such being inexpensive,
      sensitive, selective, and able to generate reproducible results using a simple
      and direct electrochemical protocol.

PMID- 16970349
TI  - Magnetophoretic velocity modulation mass analysis of a single microparticle in an
      atmosphere.
AB  - A new principle of the magnetophoretic velocity modulation mass analysis of
      microparticles, which can determine simultaneously the mass and magnetic
      susceptibility of a single microparticle, has been proposed, and the measurement
      system was constructed by applying a magnetophoretic force on a falling
      microparticle through a magnetic field gradient in an atmosphere. A polystyrene
      microparticle as a test particle adsorbed on a glass plate was selectively
      knocked off by a pulsed Nd:YAG laser impact into a narrow gap of pole pieces of
      permanent magnets having a magnetic field gradient with a maximum intensity of
      850 T2 m(-1). The falling particle was irradiated by a He-Ne laser, and the
      scattered light was detected through a slit array mask as a function of time. A
      bundle of spiked signals of scattered light intensity was analyzed to obtain
      velocities, which gave acceleration and deceleration of the falling particle. On
      the basis of the equation of motion under the magnetic field gradient, the mass
      and magnetic susceptibility of the test particle were reasonably determined.

PMID- 16970350
TI  - Increasing the sensitivity of asymmetrical flow field-flow fractionation: Slot
      outlet technique.
AB  - A new enrichment approach is described to improve the sensitivity of the
      asymmetrical flow field-flow fractionation, with and without ICPMS online
      coupling for elemental detection. For the slot outlet technique, a part of the
      laminar carrier stream is removed through an additional pump. This allowed an
      enrichment of the colloidal particles in the separation channel up to a factor of
      14. Additional improvements of the separation efficiency permitted us to separate
      colloids with differences in their molecular masses of only 2 kDa. Different
      polymer standards, proteins, and synthesized tracer colloids, as well as real
      samples (wastewater, liquid manure, serums) were used to assess the performance
      of the new technique.

PMID- 16970351
TI  - Concentration of Bacillus spores by using silica magnetic particles.
AB  - Silica particles are mainly used for the concentration of nucleic acid for
      diagnostic purposes. This is usually done under acidic or chaotropic conditions
      that will demolish most of the living organisms and prevent the application of
      other diagnostic tests. Here we describe the development of a method for the
      capturing and concentration of Bacillus spores using silica magnetic particles to
      enable fast and sensitive detection. We have shown that capturing various Bacilli
      spores via silica magnetic particles is limited, with large differences between
      spore batches (42 +/- 25%). The hydrophobic exosporium layer of spore limits the
      capture by the hydrophilic silica beads. Partial removal of Bacillus exosporium
      increases capture efficiency. To increase capturing efficiency without harming
      the spores' viability, a cationic lipid, didecyldimethylammonium bromide (DDAB),
      was used as a coat for the negatively charged silica particles. DDAB treatment
      increased capture efficiency from 42% to more than 90%. Using this method, we
      were able to capture as few as 100 Bacillus anthracis spores/mL with 90%
      efficacy. Release of captured spores was achieved by the addition of albumin. The
      capture and release processes were verified by plating and by flow cytometry
      using light scatter analysis. The method is simple, efficient, easy to operate,
      and fast.

PMID- 16970352
TI  - Pt nanoparticles: Heat treatment-based preparation and Ru(bpy)(3)2+-mediated
      formation of aggregates that can form stable films on bare solid electrode
      surfaces for solid-state electrochemiluminescence detection.
AB  - A simple thermal process for the preparation of small Pt nanoparticles is
      presented, carried out by heating a H2PtCl6/3-thiophenemalonic acid aqueous
      solution. The following treatment of such colloidal Pt solution with Ru(bpy)(3)2+
      causes the assembly of Pt nanoparticles into aggregates. Most importantly,
      directly placing such aggregates on bare solid electrode surfaces can produce
      very stable films exhibiting excellent electrochemiluminescence behaviors.

PMID- 16970354
TI  - High-accuracy quantum mechanical studies of pi-pi interactions in benzene dimers.
AB  - Although supramolecular chemistry and noncovalent interactions are playing an
      increasingly important role in modern chemical research, a detailed understanding
      of prototype noncovalent interactions remains lacking. In particular, pi-pi
      interactions, which are ubiquitous in biological systems, are not fully
      understood in terms of their strength, geometrical dependence, substituent
      effects, or fundamental physical nature. However, state-of-the-art quantum
      chemical methods are beginning to provide answers to these questions. Coupled
      cluster theory through perturbative triple excitations in conjunction with large
      basis sets and extrapolations to the complete basis set limit have provided
      definitive results for the binding energy of several configurations of the
      benzene dimer, and benchmark-quality ab initio potential curves are being used to
      calibrate new density functional and force-field models for pi-pi interactions.
      Studies of substituted benzene dimers indicate flaws in the conventional wisdom
      about substituent effects in pi-pi interactions. Three-body and four-body
      interactions in benzene clusters have also been examined.

PMID- 16970355
TI  - Time-resolved infrared absorption study of cyclopentadienyl manganese tricarbonyl
      derivatives: Chelation of pendant sulfides in acetonitrile.
AB  - The chelation dynamics of [Mn{eta5-C5H4C(O)R}(CO)3] complexes 1 (R = CH2(SCH3)),
      2 (R = CH(SCH3)2), and 3 (R = C(SCH3)3) in room-temperature acetonitrile solution
      have been investigated on the picosecond time scale by UV-pump IR-probe transient
      absorption spectroscopy. Similar to the previously observed behavior in n-heptane
      solution, irradiation of 3 in acetonitrile at 289 nm induces CO loss to
      exclusively yield a Mn-S chelated dicarbonyl product. Unlike the behavior of 1
      and 2 in n-hexane and n-heptane solutions, UV excitation of either 1 or 2 in
      acetonitrile solution induces CO loss to also exclusively yield the chelated
      products, with no evidence of a competing solvation pathway. All three complexes
      exhibit ultrafast chelation in <13 ps. Faster vibrational cooling in acetonitrile
      vs alkane solutions suggests stronger solute-solvent interaction, perhaps via
      hydrogen bonding. Ring-opening resulting from continuous irradiation of the
      pendant sulfide's chelates, [Mn{eta5-C5H4C(O)CH(SCH3)2-kappaS}(CO)2] (4) and
      [Mn{eta5-C5H4C(O)C(SCH3)3-kappaS}(CO)2] (5), is also discussed.

PMID- 16970356
TI  - Stochastic approach to data analysis in fluorescence correlation spectroscopy.
AB  - Fluorescence correlation spectroscopy (FCS) has emerged as a powerful technique
      for measuring low concentrations of fluorescent molecules and their diffusion
      constants. In FCS, the experimental data is conventionally fit using standard
      local search techniques, for example, the Marquardt-Levenberg (ML) algorithm. A
      prerequisite for these categories of algorithms is the sound knowledge of the
      behavior of fit parameters and in most cases good initial guesses for accurate
      fitting, otherwise leading to fitting artifacts. For known fit models and with
      user experience about the behavior of fit parameters, these local search
      algorithms work extremely well. However, for heterogeneous systems or where
      automated data analysis is a prerequisite, there is a need to apply a procedure,
      which treats FCS data fitting as a black box and generates reliable fit
      parameters with accuracy for the chosen model in hand. We present a computational
      approach to analyze FCS data by means of a stochastic algorithm for global search
      called PGSL, an acronym for Probabilistic Global Search Lausanne. This algorithm
      does not require any initial guesses and does the fitting in terms of searching
      for solutions by global sampling. It is flexible as well as computationally
      faster at the same time for multiparameter evaluations. We present the
      performance study of PGSL for two-component with triplet fits. The statistical
      study and the goodness of fit criterion for PGSL are also presented. The
      robustness of PGSL on noisy experimental data for parameter estimation is also
      verified. We further extend the scope of PGSL by a hybrid analysis wherein the
      output of PGSL is fed as initial guesses to ML. Reliability studies show that
      PGSL and the hybrid combination of both perform better than ML for various
      thresholds of the mean-squared error (MSE).

PMID- 16970357
TI  - Photoluminescence electron-transfer quenching of rhenium(I) rectangles with
      amines.
AB  - Electron-transfer (ET) reactions from aromatic amines to excited states of
      rhenium(I)-based molecular rectangles [{Re(CO)3(mu-bpy)Br}{Re(CO)3(mu-L)Br}]2
      (bpy = 4,4'-bipyridine, L = 4,4'-dipyridylacetylene (dpa), I; L = 4,4'
      dipyridylbutadiyne (dpb), II; and L = 1,4-bis(4'-pyridylethynyl)benzene (bpeb),
      III) were investigated in a dichloromethane solution using luminescence quenching
      techniques. Direct evidence for the ET reaction was obtained from the detection
      of the amine cation radical in this system using time-resolved transient
      absorption spectroscopy. The values of the luminescence quenching rate constants,
      kq, of the 3MLCT excited state of Re(I) rectangles with amines were found to be
      higher than those for the monomeric Re(I) complexes and other Re(I)-based
      metallacyclophanes. The observed kq values were correlated well with the driving
      force (Delta G degrees) for the ET reactions. In addition, a semiclassical theory
      of ET was successfully applied to the photoluminescence quenching of Re(I)
      rectangles with amines.

PMID- 16970358
TI  - Crystal structure, spectroscopic, and theoretical investigations of excited-state
      proton transfer in the doubly hydrogen-bonded dimer of 2-butylamino-6-methyl-4
      nitropyridine N-oxide.
AB  - The crystal structure of 2-butylamino-6-methyl-4-nitropyridine N-oxide (2B6M) was
      resolved on the basis of X-ray diffraction. Solid 2B6M occurs in the form of a
      doubly hydrogen-bonded dimer with squarelike hydrogen-bonding network composed of
      two intra- (2.556(2) A) and two intermolecular (2.891(2) A) N-H...O type hydrogen
      bonds. The molecule thus has both a protonable and a deprotonable group that led
      us to investigate the possibility of an excited-state proton transfer (ESIPT)
      reaction in different solvents by means of experimental absorption, steady state,
      and time-resolved emission spectroscopy. The results were correlated with quantum
      mechanical TD-DFT and PM3 calculations. Experimental and theoretical findings
      show the possibility of an ESIPT reaction in polar solvents. It is demonstrated
      that in particular the emission spectra of 2B6M are very sensitive to solvent
      properties, and a large value of the Stokes shift (about 8000 cm(-1)) in
      acetonitrile is indicative for an ESIPT process. This conclusion is further
      supported by time-resolved fluorescence decay measurents that show dual
      exponential decay in polar solvents. Vertical excitation energies calculated by
      TD-DFT reproduce the experimental absorption maxima in nonpolar solvents well.
      The majority of electronic transitions in 2B6M is of pi --> pi* character with a
      charge shift from the electron-donating to the electron-accepting groups. The
      calculations show that, due to the charge redistribution on excitation, the
      acidity of the amino group increases significantly, which facilitates the proton
      transfer from the amino to the N-oxide group in the excited state.

PMID- 16970359
TI  - Unimolecular decomposition of chemically activated pentatetraene (H2CCCCCH2)
      intermediates: A crossed beams study of dicarbon molecule reactions with allene.
AB  - The reactions dynamics of the dicarbon molecule C2 in the 1Sigma (g)+ singlet
      ground state and 3Pi(u) first excited triplet state with allene, H2CCCH2(X1A1),
      was investigated under single collision conditions using the crossed molecular
      beam approach at four collision energies between 13.6 and 49.4 kJ mol(-1). The
      experiments were combined with ab initio electronic structure calculations of the
      relevant stationary points on the singlet and triplet potential energy surfaces.
      Our investigations imply that the reactions are barrier-less and indirect on both
      the singlet and the triplet surfaces and proceed through bound C5H4 intermediates
      via addition of the dicarbon molecule to the carbon-carbon double bond (singlet
      surface) and to the terminal as well as central carbon atoms of the allene
      molecule (triplet surface). The initial collision complexes isomerize to form
      triplet and singlet pentatetraene intermediates (H2CCCCCH2) that decompose via
      atomic hydrogen loss to yield the 2,4-pentadiynyl-1 radical, HCCCCCH2(X2B1).
      These channels result in symmetric center-of-mass angular distributions. On the
      triplet surface, a second channel involves the existence of a nonsymmetric
      reaction intermediate (HCCCH2CCH) that fragments through atomic hydrogen emission
      to the 1,4-pentadiynyl-3 radical [C5H3(X2B1)HCCCHCCH]; this pathway was found to
      account for the backward scattered center-of-mass angular distributions at higher
      collision energies. The identification of two resonance-stabilized free C5H3
      radicals (i.e., 2,4-pentadiynyl-1 and 1,4-pentadiynyl-3) suggests that these
      molecules can be important transient species in combustion flames and in the
      chemical evolution of the interstellar medium.

PMID- 16970360
TI  - Effects of localized triplet exciton on reactivity of photoinduced omega-bond
      dissociation in naphthyl phenyl ketones having pi,pi* lowest triplet (T1) states
      studied by laser flash photolysis.
AB  - Photochemical properties of photoinduced omega-bond dissociation in naphthyl
      phenyl ketones having a phenylthiyl moiety as a leaving group, p-(alpha
      naphthoyl)benzyl phenyl sulfide (NBPS) and 4-benzoyl-1-naphthylmethyl phenyl
      sulfide (BNMPS), in solution were investigated by laser flash photolysis
      techniques. Both ketones were shown to undergo photoinduced omega-bond cleavage
      of the C-S bond to release the phenyl thiyl radical (PTR) at room temperature.
      Irrespective of excitation wavelengths of NBPS, a quantum yield (Phi(rad)) of the
      PTR formation was obtained to be 0.1, whereas that for BNMPS was found to depend
      on the excitation wavelength, i.e., absorption bands from the ground state (S0)
      to the excited singlet states, S3, S2, and S1 of BNMPS; Phi(rad)(S3) = 0.77 and
      Phi(rad)(S2) = Phi(rad)(S1) = 1.0. By using triplet sensitization of p
      phenylbenzophenone (PBP), efficiencies (alpha(rad)) of the radical formation in
      the lowest triplet state (T1(pi,pi*)) of NBPS and BNMPS were determined to be 0
      and 1.0, respectively. The agreement between Phi(rad)(S1) and alpha(rad) values
      for BNMPS indicates that the C-S bond dissociation occurs in the T1 state via the
      S1 state via a fast intersystem crossing from the S1 to the T1 state. The
      wavelength dependence of the radical yields upon direct excitation of BNMPS was
      interpreted in terms of the C-S bond cleavage in the S3 state competing with
      internal conversion from the S3 to the S2 state. The smaller value of
      Phi(rad)(S3) than those of Phi(rad)(S1) and Phi(rad)(S2) was proposed to
      originate from the geminate recombination of singlet radical pairs produced by
      the bond dissociation via the S3 state. Photoinduced omega-cleavage of NBPS was
      concluded to take place only in the S1(n,pi*) state. Difference in reactivity of
      omega-cleavage between the triplet states of NBPS and BNMPS was interpreted in
      terms of localized triplet exciton in the naphthoyl moieties.

PMID- 16970361
TI  - Product angular distribution for the H + CD4 --> HD + CD3 reaction.
AB  - Using an analytical potential energy surface previously developed by our group,
      namely PES-2002, we analyzed the gas-phase reaction between a hydrogen atom and
      perdeuterated methane. We studied the effect of quasiclassical trajectory (QCT)
      and reduced dimensionality quantum-scattering (QM) calculations, with their
      respective limitations, on CD3 product angular distributions in the collision
      energy range 16.1-46.1 kcal x mol(-1). It was found that at low collision energy,
      16.1 kcal x mol(-1), both the QCT and QM calculations yielded forward scattered
      CD3 products, i.e., a rebound mechanism. However, at high energies only the QM
      calculations on the PES-2002 surface reproduced the angular scattering found
      experimentally.

PMID- 16970362
TI  - Enhancement of sonochemical reaction rate by addition of micrometer-sized air
      bubbles.
AB  - The sonochemical reaction rate has been enhanced by the introduction of tiny air
      bubbles. The bubbles including micrometer-sized ones are produced by method of
      atomization and are introduced into aqueous luminol solution under 141-kHz
      sonication in order to investigate the enhancement of sonochemical reaction rate
      by introduction of tiny bubbles through the intensity measurement of
      sonochemiluminescence (SCL). It is shown that the introduction of tiny bubbles
      under sonication accomplishes the large SCL intensity compared to the cases of
      sonication only and liquid flow under sonication. It is also shown that it is
      important to adjust the configuration of tiny-bubble addition to the sound field.
      Through the investigations on the intensity and the spatial pattern of luminol
      SCL, it has been clarified that tiny bubbles added into the sonicated liquid not
      only cause the liquid flow but also increase the number of collapsing bubbles
      active for sonochemical reaction. It is also shown that the tiny-bubble addition
      enhances the reaction rate of KI oxidation under sonication. Therefore, the
      present method of introduction of tiny bubbles is effective for enhancement of
      sonochemical reaction rate.

PMID- 16970363
TI  - Assessing the roles of the constituents of ionic liquids in dynamic solvation:
      Comparison of an ionic liquid in micellar and bulk form.
AB  - Dynamic solvation of the dye, coumarin 153, is compared in an ionic liquid that
      forms micelles in water against the bulk solvent. This provides the unprecedented
      opportunity of investigating the behavior of the ionic liquid in two globally
      different configurations. It is proposed that the imidazolium moiety is in both
      cases responsible for the majority of the solvation, which manifests itself in
      the first 100 ps. Exploiting the use of ionic liquids capable of accommodating
      specific structures thus provides a deeper insight into how solutes interact with
      these fascinating and interesting solvents (at least those that are imidazolium
      based) that are gaining ever increasing interest in the scientific community.

PMID- 16970364
TI  - Intense photoluminescence from mixed solutions of C70 and palladium
      octaethylporphyrin: A supramolecular heavy atom effect.
AB  - Unusually intense near-infrared (near-IR) photoluminescence has been observed
      from mixed solutions of C70 and palladium octaethylporphyrin (PdOEP). The novel
      emission has a spectrum similar to C70 phosphorescence and an intensity that is
      approximately 20 times greater than that of C70 fluorescence. The emitting
      species is identified as a noncovalently bound, short-lived triplet exciplex of
      C70 with PdOEP. The emission is essentially C70 phosphorescence intensified by
      spin-orbit coupling from the Pd atom in the nearby metalloporphyrin. This
      supramolecular heavy atom effect increases the C70 emissive quantum yield to
      approximately 1 x 10(-2) in degassed hexane solution at room temperature. The
      radiative rate constant is enhanced by a factor of 10(5), to approximately 7 x
      10(4) s(-1), which is a value that exceeds the phosphorescence rate constant of
      PdOEP. Comparative studies in a rigid poly(methyl methacrylate) (PMMA) matrix
      show that the excited state of the static C70-PdOEP complex decays in
      approximately 150 ns. A Job's plot analysis shows that the complex has a 1:1
      stoichiometry. It forms dynamically in solution and is relatively weakly bound,
      with an estimated equilibrium constant near 100 M(-1). Qualitatively similar
      supramolecular heavy atom effects were also observed for complexes of PdOEP with
      C60 and fullerene derivatives.

PMID- 16970365
TI  - Photoelectron spectroscopy of free multiply charged Keggin anions alpha
      [PM12O40]3- (M = Mo, W) in the gas phase.
AB  - Two polyoxometalate Keggin-type anions, alpha-PM12O40(3-) (M = Mo, W), were
      transferred to the gas phase by electrospray; their electronic structure and
      stability were probed by photoelectron spectroscopy. These triply charged anions
      were found to be highly stable in the gas phase with large adiabatic electron
      detachment energies of 1.7 and 2.1 eV for M = Mo and W, respectively. The
      magnitude of the repulsive Coulomb barrier was measured as approximately 3.4 eV
      for both anions, providing an experimental estimate for the intramolecular
      Coulomb repulsion present in these highly charged anions. Density functional
      theory calculations were carried out and compared with the experimental data,
      providing insight into the electronic structure and valence molecular orbitals of
      the two Keggin anions. The calculations indicated that the highest occupied
      molecular orbital and other frontier orbitals for PM12O40(3-) are localized
      primarily on the mu2-oxo bridging ligands of the polyoxometalate framework,
      consistent with the reactivity on the mu2-oxo sites observed in solution. It was
      shown that the HOMO of PW12O40(3-) is stabilized relative to that of PMo12O40(3-)
      by approximately 0.35 eV. The experimental adiabatic electron detachment energies
      of PM12O40(3-) (i.e., the electron affinities of PM12O40(2-)) are combined with
      recent calculations on the proton affinity of PM12O40(3-) to yield O-H bond
      dissociation energies in PM12O39(OH)2- as approximately 5.1 eV.

PMID- 16970366
TI  - Methyl 3-methyl-2H-azirine-2-carboxylate photochemistry studied by matrix
      isolation FTIR and DFT calculations.
AB  - The aliphatic 2H-azirine, methyl 3-methyl-2H-azirine-2-carboxylate (MMAC), has
      been synthesized and its monomeric form investigated by IR spectroscopy in an
      argon matrix, at 10 K, as well as theoretically (DFT/B3LYP/6-311++G(d,p)). Two
      low-energy conformers of MMAC (Ct and Cc) were found in the matrix, both
      exhibiting the cis conformation around the C-O bond but differing in the
      arrangement around the C-C(alpha) bond. The two conformers were photoreactive
      upon in situ broadband UV excitation (lambda > 235 nm), yielding nitrile ylide
      (P1) and ketene imine (P2) type products, which resulted from cleavage of the C-C
      or C-N bond, respectively. The kinetics of the reactions leading to the formation
      of P1 and P2 are of first order, with the processes being favored when the
      reactant is in the Cc conformation. Very interestingly, the C-N bond
      photocleavage, which is unusual for aliphatic 2H-azirines, was found to be
      preferred over the generally favored in 2H-azirines C-C bond breakage. This
      behavior is attributed to the presence in the molecule of the electron
      withdrawing methoxycarbonyl substituent, which accelerates the intersystem
      crossing toward the T(1) triplet state and, in this way, favors the C-N bond
      cleavage. In addition to the primary photoprocesses leading to formation of P1
      and P2, secondary photoprocesses leading to the decarboxylation and
      decarbonylation of P2 have been also observed.

PMID- 16970367
TI  - The pi-pi stacked geometries and association thermodynamics of quinacridone
      derivatives studied by 1H NMR.
AB  - The pi-pi stacked associations of three N,N'-di(n-butyl) quinacridone
      derivatives, widely used dopants in organic light-emitting diodes, with different
      sizes of substituents were investigated in solution at various temperatures by
      (1)H NMR spectroscopy. The pi-pi stacked geometries were estimated by both the
      magnitudes of peak shifts with concentration and the directions of peak shifts
      induced by polar solvents. Two patterns of geometries with different pi-pi
      interaction strengths were found to coexist in solution for all the three
      samples. In both of the patterns, the preferential orientation of the stacking is
      the approach of the carbonyl groups on one molecule to the nitrogen atoms on the
      stacked partner, which makes the pi-deficient aromatic atoms interact with both
      pi-rich and pi-deficient aromatic atoms of the stacked partner to maximize the
      electrostatic complementarity. Differently, whereas the molecules in one pattern
      are face-to-face stacked in a parallel fashion and slip two rings relative to one
      another along with the long axis of the conjugated ring systems, the molecules in
      the other are either face-to-face stacked in an antiparallel fashion with slight
      slipping between layers or stacked in a turning fashion. Both association
      constants obtained by fitting the dilution curves and thermodynamic parameters
      obtained from van't Hoff analyses revealed unexpectedly three thermodynamic
      processes of aggregations for all the three samples in the temperature region of
      298-213 K. The size of substituents on the outer aromatic rings significantly
      influences the pi-pi stacked structures and association thermodynamics.

PMID- 16970368
TI  - Ultrafast excited state dynamics of modified phthalocyanines: p-HPcZn and p
      HPcCo.
AB  - Two modified metallophthalocyanines (MPcs) containing sulfonic naphthoxy
      substituents were synthesized. The measurements of transient absorption and time
      resolved photoluminescence were used to study the ultrafast response and excited
      state dynamics of two MPcs in dimethyl sulfoxide (DMSO) solution, which were
      predominantly in the monomeric form. Under excitation at 400 nm, these molecules
      experience vibrational relaxation to the bottom of the first excited state and
      then the excitation rapidly converts to the low-lying charge-transfer (CT) state
      and finally reaches the triplet states. Under excitation at 800 nm, they show a
      two-photon absorption character, and their excited state dynamics exhibit strong
      dependence on the probe wavelength. The main results with 400 nm pumping are
      similar to the results with 800 nm pumping. For p-HPcZn, weak two-photon
      photoluminescence was also observed with a lifetime of 52 +/- 2 ps. A four-level
      model was used to illustrate the excited state dynamics of p-HPcZn, while a five
      level model was suggested for p-HPcCo molecule.

PMID- 16970369
TI  - Metal- and ligation-dependent fragmentation of [M(1,10-Phenanthroline)(1,2,3)]2+
      cations with M = Mn, Fe, Co, Ni, Cu, and Zn: Comparison between the gas phase and
      solution.
AB  - The core ions [ML(n)]2+ with n = 1-3, where L = 1,10-phenanthroline and M is a
      first-row transition metal, have been successfully transferred from aqueous
      solution into the gas phase by electrospraying and then probed for their
      stabilities by collision-induced dissociation in a triple quadrupole mass
      spectrometer. The triply ligated metal dications [ML3]2+ were observed to
      dissociate by the extrusion of a neutral ligand, while ligand loss from both
      [ML2]2+ and [ML]2+ was accompanied by electron transfer. Comparisons are provided
      between gas-phase stabilities and stabilities for ligand loss measured in aqueous
      solution at 298 K. The measured onset for ligand loss from [ML3]2+ is quite
      insensitive to the metal, while a distinct stability order has been reported for
      aqueous solution. Low level density functional theory (DFT) calculations predict
      an intrinsic stability order for loss of ligand from [ML2]2+, but it differs from
      that in aqueous solution. Substantial agreement was obtained for the stability
      order for the loss of ligand from [ML]2+ deduced from onset energies measured for
      charge separation, computed with DFT, and reported for aqueous solution where
      hydration seems less decisive in influencing this stability order. A qualitative
      potential-energy diagram is presented that allows the energy for charge
      separation to be related to the energy for neutral ligand loss from [ML]2+ and
      shows that IE(M+) is decisive in determining the intrinsic stability order for
      loss of ligand from [ML]2+.

PMID- 16970370
TI  - Novel method for the measurement of xenon gas solubility using 129Xe NMR
      spectroscopy.
AB  - A novel method is presented for determining xenon partitioning between a gas
      phase and a liquid phase. An experimental setup which permits the simultaneous
      measurement of the 129Xe chemical shift in both the gas and the liquid phases,
      that is, under the same experimental conditions, has been designed. Xenon
      solubility is obtained via 129Xe chemical shift measurements in the gas phase.
      The method was validated against xenon solubility data from the literature; in
      general, the agreement is found to be within 3%. The solubility of xenon in three
      solvents for which data have not been previously reported (acetone, acetonitrile,
      and 1,1,2,2-tetrachloroethane) was determined using this novel method. 129Xe
      chemical shifts for dissolved xenon are also reported; it is found that xenon
      xenon interactions may play a significant role in the liquid phase even at low
      equilibrium xenon pressures.

PMID- 16970371
TI  - Matrix isolation infrared spectroscopic and theoretical study of NgMO (Ng = Ar,
      Kr, Xe; M = Cr, Mn, Fe, Co, Ni) complexes.
AB  - The matrix isolation infrared spectroscopic and quantum chemical calculation
      results indicate that late transition metal monoxides CrO through NiO coordinate
      one noble gas atom in forming the NgMO complexes (Ng = Ar, Kr, Xe; M = Cr, Mn,
      Fe, Co, Ni) in solid noble gas matrixes. Hence, the late transition metal
      monoxides previously characterized in solid noble gas matrixes should be regarded
      as the NgMO complexes, which were predicted to be linear. The M-Ng bond distances
      decrease, while the M-Ng binding energies increase from NgCrO to NgNiO. In
      contrast, the early transition metal monoxides, ScO, TiO, and VO, are not able to
      form similar noble gas atom complexes.

PMID- 16970372
TI  - Gas-phase reactions of brominated diphenyl ethers with OH radicals.
AB  - A small volume reaction chamber coupled to a mass spectrometer was used to study
      the gas-phase kinetics and mechanism of the reaction of OH radicals with diphenyl
      ether and seven polybrominated diphenyl ethers (PBDEs) with 1-2 bromines.
      Relative rate constants for these reactions were determined using isopropyl
      nitrite photolysis in He-air mixtures at approximately 740 Torr between the
      temperatures of 326-388 K. The Arrhenius expression for each compound was used to
      extrapolate the following OH rate constants at 298 K (in units of 10(-12) cm3
      molecule(-1) s(-1), with 95% confidence intervals): diphenyl ether, 7.45 +/-
      0.13; 2-bromodiphenyl ether, 4.7; 3-bromodiphenyl ether, 4.6; 4-bromodiphenyl
      ether, 5.7; 2,2'-dibromodiphenyl ether, 1.3; 2,4-dibromodiphenyl ether, 3.8; 3,3
      dibromodiphenyl ether, 3.2; and 4,4'-bromodiphenyl ether, 5.1. The measured OH
      rate constants are in reasonable agreement with those predicted by structure
      activity relationships. Positive temperature dependences of these OH rate
      constants are observed for all compounds measured except for diphenyl ether and
      4,4'-dibromodiphenyl ether. Bromophenols (in yields up to 20% relative to the
      amount of PBDE consumed) and Br2 were characterized as products of these
      reactions, suggesting that OH addition to ipso positions of these brominated
      aryls may be an important reaction pathway.

PMID- 16970373
TI  - Infrared spectroscopy of solid hydrogen sulfide and deuterium sulfide.
AB  - The infrared spectra of solid hydrogen sulfide (H2S) and deuterium sulfide (D2S)
      were collected at very low temperatures. Vapor deposition of thin films at the
      lowest temperature of 10 K produced amorphous solids while deposition at 70 K
      yielded the crystalline phase III. Infrared interference fringe patterns produced
      by the films during deposition were used to determine the film thickness. Careful
      measurement of the integrated absorbance peaks, along with the film thickness,
      allowed determination of the integrated band intensities. This report represents
      the first complete presentation of the infrared spectra of the amorphous solids.
      Observations of peaks near 3.915 and 1.982 microm (ca. 2554 and 5045 cm(-1),
      respectively) may be helpful in the conclusive identification of solid hydrogen
      sulfide on the surface of Io, a moon of Jupiter.

PMID- 16970374
TI  - Electron correlation effects in the Fe dimer.
AB  - The potential energy surface of the Fe dimer is investigated on the basis of
      density functional theory in the generalized gradient approximation (GGA).
      Electron correlation effects are taken into account explicitly within the GGA+U
      approach. We find a value of 2.20 eV for the Coulomb repulsion parameter U to
      describe the Fe dimer best, yielding a 9 Sigma(g)- ground state with an
      interatomic separation of 2.143 A. Agreement of the associated vibrational
      frequency, binding energy, ionization potential, and electron affinity with
      experimental data as well as corresponding results calculated within a high-level
      ab initio approach is improved significantly compared to conventional GGA. The
      effect of U on calculated geometric and magnetic properties of larger Fe clusters
      is discussed.

PMID- 16970375
TI  - Theoretical investigation of hydrogen bonds between CO and HNF2, H2NF, and HNO.
AB  - Ab initio quantum mechanics methods were applied to investigate the hydrogen
      bonds between CO and HNF2, H2NF, and HNO. We use the Hartree-Fock, MP2, and
      MP4(SDQ) theories with three basis sets 6-311++G(d,p), 6-311++G(2df,2p), and AUG
      cc-pVDZ, and both the standard gradient and counterpoise-corrected gradient
      techniques to optimize the geometries in order to explore the effects of the
      theories, basis sets, and different optimization methods on this type of H bond.
      Eight complexes are obtained, including the two types of C...H-N and O...H-N
      hydrogen bonds: OC...HNF2(C(s)), OC...H2NF(C(s) and C1), and OC...HNO(C(s)), and
      CO...HNF2(C(s)), CO...H2NF(C(s) and C1), and CO...HNO(C(s)). The vibrational
      analysis shows that they have no imaginary frequencies and are minima in
      potential energy surfaces. The N-H bonds exhibit a small decrease with a
      concomitant blue shift of the N-H stretch frequency on complexation, except for
      OC...HNF2 and OC...H2NF(C1), which are red-shifting at high levels of theory and
      with large basis sets. The O...H-N hydrogen bonds are very weak, with 0 K
      dissociation energies of only 0.2-2.5 kJ/mol, but the C...H-N hydrogen bonds are
      stronger with dissociation energies of 2.7-7.0 kJ/mol at the MP2/AUG-cc-pVDZ
      level. It is notable that the IR intensity of the N-H stretch vibration decreases
      on complexation for the proton donor HNO but increases for HNF2 and H2NF. A
      calculation investigation of the dipole moment derivative leads to the conclusion
      that a negative permanent dipole moment derivative of the proton donor is not a
      necessary condition for the formation of the blue-shifting hydrogen bond. Natural
      bond orbital analysis shows that for the C...H-N hydrogen bonds a large electron
      density is transferred from CO to the donors, but for the O...H-N hydrogen bonds
      a small electron density transfer exists from the proton donor to the acceptor
      CO, which is unusual except for CO...H2NF(C(s)). From the fact that the bent
      hydrogen bonds in OC(CO)...H2NF(C(s)) are quite different from those in the
      others, we conclude that a greatly bent H-bond configuration shall inhibit both
      hyperconjugation and rehybridization.

PMID- 16970376
TI  - Competition between nonclassical hydrogen-bonded acceptor sites in complexes of
      neutral AH2 Radicals (A = B, Al, and Ga): A theoretical investigation.
AB  - An ab initio computational study of the properties of the neutral AH2 radicals (A
      = B, Al, Ga) as hydrogen-bond (HB) acceptors, with H-X (X = F, Cl, Br, CN, and
      CCH) as HB donors, is carried out at the UMP2/6-311++G(2d,2p) level. Two
      different minima have been found for each of the 15 possible dimers. One
      structure corresponds to a single-electron hydrogen-bonded complex (SEHB), with
      the A atom acting as an HB acceptor. The second corresponds to a dihydrogen bond
      complex between one of the hydrogen atoms of AH2 and the H-X molecule. Thus, all
      the atoms of the neutral AH2 molecule can act as HB acceptors and none as donors.
      The stability of the SEHB complexes decreases as BH2 > AlH2 > GaH2, while for the
      dihydrogen-bonded complexes the order is AlH2 > GaH2 > BH2. For the BH2 radical
      the SEHB complexes are stronger than the dihydrogen bonded ones, while the
      opposite is found for the AlH2 and GaH2 systems. Regarding the HB donors, the
      order found for the binding energy in the two types of complexes is H2A...HF >
      H2A...HCl > H2A...HBr > H2A...HCN > H2A...HCCH.

PMID- 16970377
TI  - Aliphatic C-H/pi interactions: Methane-benzene, methane-phenol, and methane
      indole complexes.
AB  - Noncovalent C-H/pi interactions are prevalent in biochemistry and are important
      in molecular recognition. In this work, we present potential energy curves for
      methane-benzene, methane-phenol, and methane-indole complexes as prototypes for
      interactions between C-H bonds and the aromatic components of phenylalanine,
      tyrosine, and tryptophan. Second-order perturbation theory (MP2) is used in
      conjunction with the aug-cc-pVDZ and aug-cc-pVTZ basis sets to determine the
      counterpoise-corrected interaction energy for selected complex configurations.
      Using corrections for higher-order electron correlation determined with coupled
      cluster theory through perturbative triples [CCSD(T)] in the aug-cc-pVDZ basis
      set, we estimate, through an additive approximation, results at the very accurate
      CCSD(T)/aug-cc-pVTZ level of theory. Symmetry-adapted perturbation theory (SAPT)
      is employed to determine the physically significant components of the total
      interaction energy for each complex.

PMID- 16970378
TI  - Raman spectroscopic study on the hydration structures of tetraethylammonium
      cation in water.
AB  - Conformational changes of tetraethylammonium ion (Et4N+) in aqueous solution have
      been studied by Raman spectroscopy as functions of pressure and concentration.
      The difference in the partial molar volume (Delta V(tg x tg-->tt x tt)) between
      the trans-gauche x trans-gauche (tg x tg) and trans-trans x trans-trans (tt x tt)
      conformers of Et4N+ ion has been calculated from the pressure dependence of the
      relative Raman intensity ratio between the conformers. We discuss about the Delta
      V(tg x tg-->tt x tt) with two contributions from the molecular and hydration
      volumes. Delta V(tg x tg-->tt x tt) is found to be negative, and this is mainly
      due to the large molecular volume contribution. The value of Delta V(tg x tg-->tt
      x tt) becomes smaller with increasing R probably due to the hydration volume
      contribution. In view of the pressure and concentration dependences, the water
      molecules around Et4N+ ions at R = 19 (R= moles of water/moles of salt) mainly
      form the hydrophobic hydration. The hydrophobic hydration may prefer the tt x tt
      conformer to the tg x tg conformer. On the other hand, the hydration structure at
      R = 4 no longer forms the hydrophobic hydration and changes to another type of
      hydration, where the medium H-bond component is the dominant species. The
      increase of the ion-ion interactions with decreasing R induces large fractions of
      the tg x tg conformer.

PMID- 16970379
TI  - Theoretical study of the Ar-, Kr-, and Xe-CH4, -CF4 intermolecular potential
      energy surfaces.
AB  - We present a theoretical study of the intermolecular potentials for the Ar, Kr,
      and Xe-CH4, -CF4 systems. The potential-energy surfaces of these systems have
      been calculated utilizing second-order Moller-Plesset perturbation theory and
      coupled-cluster theory in combination with correlation-consistent basis sets (aug
      cc-pvnz; n = d, t, q). The calculations show that the stabilizing interactions
      between the rare gases and the molecules are slightly larger for CF4 than for
      CH4. Moreover, the rare-gas-CX4 (X = H, F) potentials are more attractive for Xe
      than for Kr and Ar. Our highest quality ab initio data (focal-point-CCSD(T)
      extrapolated to the complete basis set limit) have been used to develop pairwise
      analytical potentials for rare-gas-hydrocarbon (-fluorocarbon) systems. These
      potentials can be applied in classical-trajectory studies of rare gases
      interacting with hydrocarbon surfaces.

PMID- 16970380
TI  - Theoretical nitrogen NMR chemical shifts in octahedral boron nitride cages.
AB  - We have calculated the geometrical structure, relative stability, and nitrogen
      chemical shifts of five boron nitride hollow octahedral cages using density
      functional theory. Our results show three typical ranges for nitrogen chemical
      shifts corresponding to each of the nonequivalent magnetic sites of the N atoms.
      The principal component of the electric field gradient tensor at each 14N site in
      boron nitride cages is predicted to be much smaller than the corresponding value
      in borazine, which should reflect in sharper spectral lines and much better
      resolution.

PMID- 16970381
TI  - Relationship between the charge distribution and dipole moment functions of CO
      and the related molecules CS, SiO, and SiS.
AB  - The dipole moment functions of the titled molecules are written as the sum of a
      charge and induced atomic dipole contribution and the distance dependence
      interpreted in terms of these components. These two contributions have opposite
      signs over a large range of internuclear distances, and when they have equal
      magnitudes, the dipole moment vanishes. This happens with CO near the equilibrium
      bond length and is responsible for its small dipole moment. The dipole moment of
      CS is 0.770(ea0), rather large for a diatomic in which the two atoms have
      essentially the same electronegativities; this is because for CS, the two
      components of the dipole moment have the same sign at equilibrium and reinforce
      one another.

PMID- 16970382
TI  - Inherent structures of crystalline tetracene.
AB  - We have systematically sampled the potential energy surface of crystalline
      tetracene to identify its local minima. These minima represent all possible
      stable configurations and constitute the "inherent structures" of the system. The
      crystal is described in terms of rigid molecules with Coulombic and atom-atom
      interactions. Hundreds of distinct minima are identified, mostly belonging to the
      space groups P (triclinic) and P2(1)/c (monoclinic), with a variety of structural
      arrangements. The deepest minimum corresponds to the high temperature-low
      pressure polymorph. This is the only polymorph with a completely described X-ray
      structure, which is satisfactorily described by the calculations. The next deep
      minimum is likely to correspond to the low temperature-high pressure polymorph,
      which has been experimentally identified but not yet fully described.

PMID- 16970383
TI  - Quantum chemical investigation of low-temperature intramolecular hydrogen
      transfer reactions of hydrocarbons.
AB  - The B3LYP functional was evaluated as a method to calculate reaction barriers and
      structure-reactivity relationships for intramolecular hydrogen transfer reactions
      involving peroxy radicals. Nine different basis sets as well as five other MO/DFT
      and hybrid methods were used in comparing three reactions to available
      experimental data. It was shown that B3LYP/6-311+G(d,p) offers a good compromise
      between speed and accuracy for studies in which thermodynamic and kinetic data of
      many reactions are required. Sixteen reactions were studied to develop structure
      reactivity relationships to correlate the activation energy with the heat of
      reaction. As long as no structural heterogeneities were present in the transition
      state ring, a simple Evans-Polanyi relationship was shown to capture the
      activation energy as a function of heat of reaction for reactions in the 1,5
      hydrogen shift family. For peroxy radicals undergoing self-abstraction of a
      hydrogen atom in the 1,5-position, the activation energy was calculated as E(a)
      (kcal mol(-1)) = 6.3 + Delta H(rxn) (kcal mol(-1)). For reactions with a carbonyl
      group embedded in the ring of the transition state, the activation energy of
      peroxy radicals undergoing self-abstraction was correlated as E(a) (kcal mol(-1))
      = 18.1 + 0.74 Delta H(rxn) (kcal mol(-1)). The impact of the size of the
      transition state ring on the activation energy and pre-exponential factor was
      also probed, and it was shown that these effects can be described using simple
      nonlinear and linear fits, respectively.

PMID- 16970384
TI  - Geometrical features of hydrogen bonded complexes involving sterically hindered
      pyridines.
AB  - The ability of strongly sterically hindered pyridines to form hydrogen bonded
      complexes was inspected using low-temperature 1H and 15N NMR spectroscopy in a
      liquefied Freon mixture. The proton acceptors were 2,6-di(tert-butyl)-4-methyl-
      and 2,6-di(tert-butyl)-4-diethylaminopyridine; the proton donors were hydrogen
      tetrafluoroborate, hydrogen chloride, and hydrogen fluoride. The presence of the
      tert-butyl groups in the ortho positions dramatically perturbed the geometry of
      the forming hydrogen bonds. As revealed by experiment, the studied crowded
      pyridines could form hydrogen bonded complexes with proton donors exclusively
      through their protonation. Even the strongest small proton acceptor, anion F-,
      could not be received by the protonated base. Instead, the simplest hydrogen
      bonded complex involved the [FHF]- anion. This complex was characterized by the
      shortest possible N...F distance of about 2.8 A. Because the ortho tert-butyl
      groups did not prevent the hydrogen bond interaction between the protonated
      center and the anion completely, an increase of the pyridine basicity caused a
      further shortening of the N-H distance and a weakening of the hydrogen bond to
      the counterion.

PMID- 16970385
TI  - Dissociation mechanism of a stable intermediate: perfluorohydroxylamine.
AB  - The mechanism of dissociation of F2NOF has been studied using density-functional
      (B3LYP, BB1K, and MPWB1K) and wave function methods (CCSD). Variational
      transition state theory was used to calculate the rate constants for cis-F2NOF -
      > FNO + F2 (concerted), cis-F2NOF --> F2NO + F, and cis-F2NOF --> trans-F2NOF -->
      F3NO. Rate constants were also calculated for the dissociation of F2NOF by using
      transition state theory. The enthalpies of the transitions states (CCSD(T)/cc
      pVQZ//B3LYP/6-311+G(d)) were very close to the enthalpy of separated F2NO + F
      radicals which implies temperature-dependent competition between concerted
      rearrangement and fragmentation-recombination. The picture is further complicated
      by the fact that F2NO undergoes fragmentation into FNO + F with a very low
      barrier. Thus, formation of F3NO, the global minimum on the potential energy
      surface, can only occur by a concerted process (not from F2NO + F). The data were
      fit to a temperature-dependent rate in the range 200-1000 K in the form k2 = 8.14
      x 10(13) exp(-7860/T) s(-1), k(1) = 6.37 x 10(13) exp(-7855/T) s(-1), and k(10) =
      1.42 x 10(12) exp(-7420/T) for cis-F2NOF --> FNO + F2 (concerted), cis-F2NOF -->
      F2NO + F, and cis-F2NOF --> F3NO, respectively. The calculated lifetime of cis
      F2NOF at 298K is 2.5 x 10(-3) s via k1.

PMID- 16970386
TI  - Estimates of the energy of intramolecular hydrogen bonds.
AB  - A method for the estimation of the energy of intramolecular hydrogen bonds in
      conjugated systems existing in a variety of conformations is presented. The
      method is applied to determine the intramolecular hydrogen bond energy in 3
      aminopropenal and 3-aminopropenthial. According to the proposed estimation
      scheme, the intramolecular H-bond energies are found to be of the order of 5-7
      kcal/mol. These results are compared with those obtained by using other
      estimation schemes as well as with the recent results by other authors. Also, the
      H-bond energies in dimers and trimers of the two molecules are calculated and
      compared with the corresponding data for internally hydrogen-bonded monomers.
      This comparison shows that the bond equalization effect is primarily due to
      proton donor-proton acceptor proximity. In comparison with intermolecular
      hydrogen bonds, the rigidity of the chelate skeleton enhances this proximity
      effect. The same effect can be seen in systems with intermolecular hydrogen
      bonds, although its magnitude is diminished because of the absence of additional
      forces which pull the proton donor and proton acceptor groups toward each other.
      No specific resonance-assisted origin of the intramolecular hydrogen bond energy
      seems to be needed to elucidate the energetics of these bonds.

PMID- 16970387
TI  - Structure and energetics of gaseous HZnCl.
AB  - The HZnCl molecule has recently been observed both in the gas phase and in argon
      matrixes, and the complexity of its spectrum has created big discrepancies
      between experimental and theoretically predicted Zn-H bond distances. In an
      attempt to resolve the questionable H-ZnCl bond length issue, as well as to study
      its stability relative to bond breakage, we have investigated at a very high ab
      initio level its geometric and energetic parameters. At the coupled cluster level
      of theory [CCSD(T)] with the new correlation-consistent basis sets for Zn by
      Balabanov and Peterson, and with the inclusion of core/valence and one-electron
      Douglas-Kroll-Hess relativistic effects, the basis set extrapolated H-ZnCl and
      HZn-Cl bond lengths have been calculated to be 1.499 and 2.079 A, compared with
      the experimental estimates of 1.596-1.789 and 2.08346 A, respectively. With the
      same procedure, the experimentally unknown bond length of ground-state ZnCl has
      been found to be equal to 2.122 A. As in the free diatomics ZnCl and ZnH, the HZn
      Cl bond is stronger than the H-ZnCl bond by about 30 kcal/mol.

PMID- 16970388
TI  - Theoretical study of the substituent effects on the S-H bond dissociation energy
      and ionization energy of 3-pyridinethiol: Prediction of novel antioxidant.
AB  - The S-H bond dissociation enthalpies [BDE(S-H)] of a set of 5-X- and 6-X-3
      pyridinethiols (X = F, Cl, CH3, OCH3, NH2, N(CH3)2, CF3, CN, and NO2) have been
      computed using the density functional theory based (RO)B3LYP procedure with 6
      311++G(2df,2p) basis set. The effects of substituents on the BDE(S-H), proton
      affinity of the pyridinethiol anion [PA(S-)] and ionization energy (IE) are
      analyzed and their correlations with Hammett's substituent constants are
      examined. Subsequently, a series of 6-substituted 3-pyridinethiols have been
      explored to find out their antioxidant potentials. Finally, a number of 3
      pyridinethiol based compounds are theoretically proposed as novel antioxidants.

PMID- 16970389
TI  - The reaction of nitrogen atoms with methyl radicals: Are spin-forbidden channels
      important?
AB  - A computational study of the N(4S) + CH3 reaction has been carried out. The
      reactants approach through an attractive potential surface leading to an
      intermediate, H3CN, whose formation does not involve any barrier. In agreement
      with the experimental results, the dominant channel for this reaction is H2CN+H.
      The theoretically estimated rate coefficient for the overall process at 298 K is
      9.1 x 10(-12) cm3 s(-1) molecule(-1), which is nearly 1 order of magnitude lower
      than the experimental result, but also much larger than those computed for the
      reactions of ground-state nitrogen atoms with halomethyl radicals. The analysis
      of the singlet potential energy surface, and the corresponding computational
      kinetic study, shows that for the reaction of excited nitrogen atoms with methyl
      radicals, the preferred product from the kinetic point of view is also H2CN+H,
      but in this case production of HCN is significant (with branching ratios around
      0.185). According to our calculations, spin-forbidden processes are highly
      unlikely for the N(4S) + CH3 reaction. However, further evolution of the
      preferred products, H2CN+H, might explain the experimental observation of
      hydrogen cyanide as a minor product in this reaction.

PMID- 16970390
TI  - Fumarranol, a rearranged fumagillin analogue that inhibits angiogenesis in vivo.
AB  - The fumagillin family of natural products inhibits angiogenesis through the
      irreversible inhibition of the type 2 methionine aminopeptidase (MetAP2). Herein
      is reported a novel fumagillin analogue named fumarranol. It is shown that, like
      fumagillin, fumarranol selectively inhibits MetAP2 and endothelial cell
      proliferation. It is also active in a mouse model of angiogenesis in vivo. Unlike
      TNP-470, fumarranol does not covalently bind to MetAP2. Fumarranol may serve as a
      lead for a new class of angiogenesis inhibitors.

PMID- 16970391
TI  - Design and synthesis of dual peroxisome proliferator-activated receptors gamma
      and delta agonists as novel euglycemic agents with a reduced weight gain profile.
AB  - The design and synthesis of the dual peroxisome proliferator-activated receptor
      (PPAR) gamma/delta agonist (R)-3-{4-[3-(4-chloro-2-phenoxy-phenoxy)-butoxy]-2
      ethyl-phenyl}-propionic acid (20) for the treatment of type 2 diabetes and
      associated dyslipidemia is described. The compound possesses a potent dual hPPAR
      gamma/delta agonist profile (IC(50) = 19 nM/4 nM; EC(50) = 102 nM/6 nM for
      hPPARgamma and hPPARdelta, respectively). In preclinical models, the compound
      improves insulin sensitivity and reverses diabetic hyperglycemia with less weight
      gain at a given level of glucose control relative to rosiglitazone.

PMID- 16970392
TI  - Identification of a novel 4-aminomethylpiperidine class of M3 muscarinic receptor
      antagonists and structural insight into their M3 selectivity.
AB  - Identification of a novel class of potent and highly selective M(3) muscarinic
      antagonists is described. First, the structure-activity relationship in the
      cationic amine core of our previously reported triphenylpropionamide class of
      M(3) selective antagonists was explored by a small diamine library constructed in
      solid phase. This led to the identification of M(3) antagonists with a novel
      piperidine pharmacophore and significantly improved subtype selectivity from a
      previously reported class. Successive modification on the terminal
      triphenylpropionamide part of the newly identified class gave 14a as a potent
      M(3) selective antagonist that had >100-fold selectivity versus the M(1), M(2),
      M(4), and M(5) receptors (M(3): K(i) = 0.30 nM, M(1)/M(3) = 570-fold, M(2)/M(3) =
      1600-fold, M(4)/M(3) = 140-fold, M(5)/M(3) = 12000-fold). The possible rationale
      for its extraordinarily higher subtype selectivity than reported M(3) antagonists
      was hypothesized by sequence alignment of multiple muscarinic receptors and a
      computational docking of 14a into transmembrane domains of M(3) receptors.

PMID- 16970393
TI  - Design and biological evaluation of novel tubulin inhibitors as antimitotic
      agents using a pharmacophore binding model with tubulin.
AB  - Although the structure has been elucidated for the binding of colchicine and
      podophyllotoxin as potent destabilizer for microtubule formation, very little is
      known about MDL-27048, a competitive inhibitor for colchicine and
      podophyllotoxin. The structural basis for the interaction of antimitotic agents
      with tubulin was investigated by molecular modeling, and we propose binding
      models for MDL-27048 against tubulin. The proposed model was not only consistent
      with previous competition experiment data between colchicine and MDL-27048, but
      further suggested an additional binding cavity on tubulin. Based on this finding
      from the proposed MDL-tubulin complex, we performed molecular design studies to
      identify new antimitotic agents. These new chalcone derivatives exerted growth
      inhibitory effects on all four human hepatoma and one renal epithelial cell lines
      tested and induced strong cell cycle arrest at G2/M phase. Furthermore, these
      compounds exhibited a strong inhibitory effect on tubulin polymerization in
      vitro. Therefore, we suggest that the validated MDL-27048 model would serve as a
      potent platform for designing new molecular entities for anticancer agents
      targeted to microtubules.

PMID- 16970394
TI  - Discovery of aminoquinazolines as potent, orally bioavailable inhibitors of Lck:
      synthesis, SAR, and in vivo anti-inflammatory activity.
AB  - The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src
      family expressed in T cells and natural killer (NK) cells. Genetic evidence in
      both mice and humans demonstrates that Lck kinase activity is critical for
      signaling mediated by the T cell receptor (TCR), which leads to normal T cell
      development and activation. Selective inhibition of Lck is expected to offer a
      new therapy for the treatment of T-cell-mediated autoimmune and inflammatory
      disease. Screening of our kinase-preferred collection identified aminoquinazoline
      1 as a potent, nonselective inhibitor of Lck and T cell proliferation. In this
      report, we describe the synthesis and structure-activity relationships of a
      series of novel aminoquinazolines possessing in vitro mechanism-based potency.
      Optimized, orally bioavailable compounds 32 and 47 exhibit anti-inflammatory
      activity (ED(50) of 22 and 11 mg/kg, respectively) in the anti-CD3-induced
      production of interleukin-2 (IL-2) in mice.

PMID- 16970395
TI  - Iminosugars as potential inhibitors of glycogenolysis: structural insights into
      the molecular basis of glycogen phosphorylase inhibition.
AB  - Iminosugars DAB (5), isofagomine (9), and several N-substituted derivatives have
      been identified as potent inhibitors of liver glycogen phosphorylase a (IC(50) =
      0.4-1.2 microM) and of basal and glucagon-stimulated glycogenolysis (IC(50) = 1-3
      microM). The X-ray structures of 5, 9, and its N-3-phenylpropyl analogue 8 in
      complex with rabbit muscle glycogen phosphorylase (GPb) shows that iminosugars
      bind tightly at the catalytic site in the presence of the substrate phosphate and
      induce conformational changes that characterize the R-state conformation of the
      enzyme. Charged nitrogen N1 is within hydrogen-bonding distance with the carbonyl
      oxygen of His377 (5) and in ionic contact with the substrate phosphate oxygen (8
      and 9). Our findings suggest that the inhibitors function as oxocarbenium ion
      transition-state analogues. The conformational change to the R state provides an
      explanation for previous findings that 5, unlike inhibitors that favor the T
      state, promotes phosphorylation of GPb in hepatocytes with sequential
      inactivation of glycogen synthase.

PMID- 16970396
TI  - Virtual screening for aryl hydrocarbon receptor binding prediction.
AB  - The overall goal of this study has been to validate computational models for
      predicting aryl hydrocarbon receptor (AhR) binding. Due to the unavailability of
      the AhR X-ray crystal structure we have decided to use QSARs models for the
      binding prediction virtual screening. We have built up CoMFA, Volsurf, and HQSAR
      models using as a training set 84 AhR ligands. Additionally, we have built a
      hybrid model combining two of the final selected models in order to give a single
      operational system. The results show that CoMFA, VolSurf, HQSAR, and the hybrid
      models gives good results (R(2) equal to 0.91, 0.79, 0.85, and 0.82 and q(2)
      0.62, 0.58, 0.62, and 0.70, respectively). Since the techniques analyzed show a
      good correlation and good prediction also for an external test set, particularly
      the HQSAR and the hybrid model, we can conclude that these models can be used for
      predicting AhR binding in virtual screening.

PMID- 16970397
TI  - Structurally simple, potent, Plasmodium selective farnesyltransferase inhibitors
      that arrest the growth of malaria parasites.
AB  - Third world nations require immediate access to inexpensive therapeutics to
      counter the high mortality inflicted by malaria. Here, we report a new class of
      antimalarial protein farnesyltransferase (PFT) inhibitors, designed with specific
      emphasis on simple molecular architecture, to facilitate easy access to therapies
      based on this recently validated antimalarial target. This novel series of
      compounds represents the first Plasmodium falciparum selective PFT inhibitors
      reported (up to 145-fold selectivity), with lead inhibitors displaying excellent
      in vitro activity (IC(50) < 1 nM) and toxicity to cultured parasites at low
      concentrations (ED(50) < 100 nM). Initial studies of absorption, metabolism, and
      oral bioavailability are reported.

PMID- 16970398
TI  - Design, synthesis, and evaluation of aza-peptide Michael acceptors as selective
      and potent inhibitors of caspases-2, -3, -6, -7, -8, -9, and -10.
AB  - Aza-peptide Michael acceptors are a novel class of inhibitors that are potent and
      specific for caspases-2, -3, -6, -7, -8, -9, and -10. The second-order rate
      constants are in the order of 10(6) M(-1) s(-1). The aza-peptide Michael acceptor
      inhibitor 18t (Cbz-Asp-Glu-Val-AAsp-trans-CH=CH-CON(CH(2)-1-Naphth)(2) is the
      most potent compound and it inhibits caspase-3 with a k(2) value of 5620000 M(-1)
      s(-1). The inhibitor 18t is 13700, 190, 6.4, 594, 37500, and 173-fold more
      selective for caspase-3 over caspases-2, -6, -7, -8, -9, and -10, respectively.
      Aza-peptide Michael acceptors designed with caspase specific sequences are
      selective and do not show any cross reactivity with clan CA cysteine proteases
      such as papain, cathepsin B, and calpains. High-resolution crystal structures of
      caspase-3 and caspase-8 in complex with aza-peptide Michael acceptor inhibitors
      demonstrate the nucleophilic attack on C2 and provide insight into the
      selectivity and potency of the inhibitors with respect to the P1' moiety.

PMID- 16970399
TI  - Synthesis of adenophostin A analogues conjugating an aromatic group at the 5'
      position as potent IP3 receptor ligands.
AB  - Previous structure-activity relationship studies of adenophostin A, a potent
      IP(3) receptor agonist, led us to design the novel adenophostin A analogues 5a-c,
      conjugating an aromatic group at the 5'-position to develop useful IP(3) receptor
      ligands. The common key intermediate, a D-ribosyl alpha-D-glucoside 10alpha, was
      stereoselectively synthesized by a glycosidation with the 1-sulfinylglucoside
      donor 11, which was conformationally restricted by a 3,4-O-cyclic diketal
      protecting group. After introduction of an aromatic group at the 5-position of
      the ribose moiety, an adenine base was stereoselectively introduced at the
      anomeric beta-position to form 7a-c, where the tetra-O-i-butyryl donors 9a-c were
      significantly more effective than the corresponding O-acetyl donor. Thus, the
      target compounds 5a-c were synthesized via phosphorylation of the 2', 3' ', and
      4' '-hydroxyls. The potencies of compounds 5a-c for Ca(2+) release were shown to
      be indistinguishable from that of adenophostin A, indicating that bulky
      substitutions at the 5'-position of adenophostin A are well-tolerated in the
      receptor binding. This biological activity of 5a-c can be rationalized by
      molecular modeling using the ligand binding domain of the IP(3) receptor.

PMID- 16970400
TI  - Structural insights into the ATP binding pocket of the anaplastic lymphoma kinase
      by site-directed mutagenesis, inhibitor binding analysis, and homology modeling.
AB  - Anaplastic lymphoma kinase (ALK) is a valid target for anticancer therapy;
      however, potent ALK inhibitors suitable for clinical use are lacking. Because the
      majority of described kinase inhibitors bind in the ATP pocket of the kinase
      domain, we have characterized this pocket in ALK using site-directed mutagenesis,
      inhibition studies, and molecular modeling. Mutation of the gatekeeper residue, a
      key structural determinant influencing inhibitor binding, rendered the fusion
      protein, NPM/ALK, sensitive to inhibition by SKI-606 in the nanomolar range,
      while PD173955 inhibited the NPM/ALK mutant at micromolar concentrations. In
      contrast, both wild type and mutant NPM/ALK were insensitive to imatinib.
      Computer modeling indicated that docking solutions obtained with a homology model
      representing the intermediate conformation of the ALK kinase domain reflected
      closely experimental data. The good agreement between experimental and virtual
      results indicate that the ALK molecular models described here are useful tools
      for the rational design of ALK selective inhibitors. In addition, 4-phenylamino
      quinoline compounds may have potential as templates for ALK inhibitors.

PMID- 16970401
TI  - [4-(imidazol-1-yl)thiazol-2-yl]phenylamines. A novel class of highly potent
      colchicine site binding tubulin inhibitors: synthesis and cytotoxic activity on
      selected human cancer cell lines.
AB  - Synthesis and cytotoxic activity in the submicromolar range of a series of [4
      (imidazol-1-yl)thiazol-2-yl]phenylamines are described. Cell cycle dependent
      cytotoxicity on RKO human colon carcinoma cells with inducible expression of
      p27(kip1) and the influence on microtubule formation were investigated.
      Considering the significant correlation between the IC(50) values of tubulin
      polymerization inhibition, [(3)H]colchicine competition, and cytotoxicity of the
      investigated compounds, tubulin is the main cellular target. The inhibition of
      microtubule formation was shown to be mediated by interference with the
      colchicine binding site of tubulin. In depth analysis of the investigated
      compounds allowed the identification of modifications that altered the
      pharmacological profile of the compounds from a mitosis-inducing phenotype to a
      G1 cell cycle arresting phenotype.

PMID- 16970402
TI  - HIV-1 protease mutations and inhibitor modifications monitored on a series of
      complexes. Structural basis for the effect of the A71V mutation on the active
      site.
AB  - Two new X-ray structures of an HIV-1 protease mutant (A71V, V82T, I84V) in
      complex with inhibitors SE and SQ, pseudotetrapeptide inhibitors with an acyclic
      S-hydroxyethylamine isostere, were determined. Comparison of eight structures
      exploring the binding of four similar inhibitors--SE, SQ (S-hydroxyethylamine
      isostere), OE (ethyleneamine), and QF34 (hydroxyethylene)--to wild-type and
      A71V/V82T/I84V HIV-1 protease elucidates the principles of altered interaction
      with changing conditions. The A71V mutation, which is distant from the active
      site, causes changes in the structure of the enzyme detectable by the means of X
      ray structure analysis, and a route of propagation of the effect toward the
      active site is proposed.

PMID- 16970403
TI  - Diphenyl phosphonate inhibitors for the urokinase-type plasminogen activator:
      optimization of the P4 position.
AB  - This paper describes the structure-activity relationship in a series of
      tripeptidyl diphenyl phosphonate irreversible urokinase plasminogen activator
      (uPA) inhibitors, originally derived from an arginyltripeptide. uPA is considered
      an interesting target in anticancer drug design. The selectivity of these
      inhibitors for uPA is enhanced by the optimization of the P4 position. The most
      interesting compound shows an IC(50) of 5 nM, with a selectivity index of more
      than 3000 toward other Arg/Lys-specific proteases such as tissue-type plasminogen
      activator, plasmin, factor Xa, and thrombin. A synthetic strategy for the
      preparation of small libraries of diphenyl phosphonate analogues of capped
      tripeptides is described. It is shown that uPA is irreversibly inhibited, and
      interactions with the active site were modeled. Finally, a diparacetamol
      phosphonate analogue was developed to circumvent the release of cytotoxic phenol.

PMID- 16970404
TI  - 1-Aminomethylbenzocycloalkanes: conformationally restricted hallucinogenic
      phenethylamine analogues as functionally selective 5-HT2A receptor agonists.
AB  - A series of conformationally restricted analogues of the hallucinogenic
      phenethylamine 1 (2,5-dimethoxy-4-bromophenethylamine, 2C-B) was synthesized to
      test several hypotheses concerning the bioactive conformation of phenethylamine
      ligands upon binding to the 5-HT(2A) receptor. These benzocycloalkane analogues
      were assayed for their receptor binding affinity and ability to activate
      downstream signaling pathways, and one exceptional compound was selected for
      testing in an in vivo drug discrimination model of hallucinogenesis. All
      compounds were examined in silico by virtual docking into a homology model of the
      5-HT(2A) receptor. On the basis of these docking experiments, it was predicted
      that the R enantiomer of benzocyclobutene analogue 2 would be the most potent.
      Subsequent chemical resolution and X-ray crystallography confirmed this
      prediction, as (R)-2 proved to be equipotent to LSD in rats trained to
      discriminate LSD from saline. Thus, we propose that the conformation of 2 mimics
      the active binding conformation of the more flexible phenethylamine type
      hallucinogens. In addition, (R)-2 is one of the most potent and selective
      compounds yet discovered in the in vivo drug discrimination assay. Further, 2 was
      found to be a functionally selective agonist at the 5-HT(2A) receptor, having 65
      fold greater potency in stimulating phosphoinositide turnover than in producing
      arachidonic acid release. If hallucinogenic effects are correlated with
      arachidonic acid production, such functionally selective 5-HT(2A) receptor
      agonists may lack the intoxicating properties of hallucinogens such as LSD.

PMID- 16970405
TI  - Activity of nitrogen-containing and non-nitrogen-containing bisphosphonates on
      tumor cell lines.
AB  - We synthesized and tested three series of bisphosphonates for their activity in
      inhibiting the growth of three human tumor cell lines: MCF-7 (breast), NCI-H460
      (lung), and SF-268 (CNS). The first series of compounds consisted of 49 nitrogen
      containing bisphosphonates, the most active species being a
      tetrakispivaloyloxymethyl (POM) ester, having an (average) IC(50) of 6.8 microM.
      The second series of compounds consisted of nine terphenylbisphosphonates, the
      most active species also being a POM ester, having an IC(50) of 2.2 microM. The
      third series of compounds consisted of seven halogen or
      cyanophenylbisphosphonates, the most active species again being a POM ester,
      having an IC(50) of 500 nM. Taken together, these results are of interest because
      they show that bisphosphonate esters can have potent activity against a variety
      of tumor cell lines, with the most active terphenyl- and halophenyl-containing
      species having IC(50) values approximately 10-40x lower than the most potent
      commercially available bisphosphonates.

PMID- 16970406
TI  - Convenient nonlinear model for predicting the tissue/blood partition coefficients
      of seven human tissues of neutral, acidic, and basic structurally diverse
      compounds.
AB  - In this work, the tissue/blood partition coefficients of seven human tissues were
      calculated using a nonlinear regression analysis. The dataset contained 80
      structurally diverse compounds distributing into the brain, kidney, muscle, lung,
      liver, heart, and fat, whose acidic and basic properties were also considered by
      introducing the three possible forms of the compound in the human body (neutral,
      cationic, and anionic forms). A total of 248 data points were there in the
      training set (eq 5: r = 0.877, s = 0.352; eq 6: r = 0.869, s = 0.362) and 49 data
      points in the testing set (eq 5: r = 0.844, s = 0.342; eq 6: r = 0.860, s =
      0.311). It was also concluded that the same state (neutral, cation, and anion) of
      a compound has essentially identical partition coefficients between the same
      tissue composition and the blood in these tissues. Only the different content of
      the three tissue compositions (lipid, protein, and water) lead to the different
      partition coefficient in different tissues, which offered a significant
      conclusion for the drug's distribution research.

PMID- 16970407
TI  - Isolation, structure elucidation, total synthesis, and evaluation of new natural
      and synthetic ceramides on human SK-MEL-1 melanoma cells.
AB  - Two new long-chain ceramides, trametenamides A (1) and B (2), were isolated from
      the methanolic extract of the fruiting body of the fungus Trametes menziesii. The
      structures were elucidated by spectroscopic analyses and chemical
      transformations, and the absolute stereochemistry of trametenamide B (2) was
      determined by stereoselective total synthesis of four possible diastereomers. The
      acetyl derivative of the natural ceramide (1a) and synthetic ceramides (24-27)
      showed cytotoxicity on the human melanoma cell line SK-MEL-1, which was caused by
      induction of apoptosis as determined by DNA fragmentation, poly(ADP-ribose)
      polymerase cleavage, and procaspase-9 and -8 processing.

PMID- 16970409
TI  - Discovery of antiglioma activity of biaryl 1,2,3,4-tetrahydroisoquinoline
      derivatives and conformationally flexible analogues.
AB  - Cultured rat astrocytes and C6 rat glioma were used as a differential screen for
      a variety of 1,2,3,4-tetrahydroisoquinoline (THI) derivatives. Compound 1 [1
      (biphenyl-4-ylmethyl)-1,2,3,4-tetrahydroisoquinoline-6,7-diol hydrochloride]
      selectively blocked the growth of C6 glioma leaving normal astrocytes relatively
      unaffected. The potential for clinical utility of 1 was further substantiated in
      human gliomas and other tumor cell lines. Preliminary SAR of this activity was
      characterized by synthesis and testing of several THI and conformationally
      flexible variants.

PMID- 16970412
TI  - On a mechanism of low-pressure insertion of chain molecules into crystalline
      matrices.
AB  - A microscopic mechanism of low-pressure insertion and separation of chain-like
      molecules in host matrices is proposed. It is shown that the intramolecular
      correlations combined to appropriate host activities are responsible for a low
      pressure condensation of chain molecules. This allows to recover a fine structure
      of the isotherms and to explain recent experiments on the insertion of C(2)H(2)
      and CO(2) guest species into metal-organic microporous materials. We argue that
      the mechanism should be dominant in low-dimensional host geometries, where the
      effects related to the chain conformations or reorientations are strongly
      suppressed and the major factors are the chain connectivity and the segment
      packing.

PMID- 16970408
TI  - Pyrrolo[1,2-b][1,2,5]benzothiadiazepines (PBTDs): A new class of agents with high
      apoptotic activity in chronic myelogenous leukemia K562 cells and in cells from
      patients at onset and who were imatinib-resistant.
AB  - Pyrrolo[1,2-b][1,2,5]benzothiadiazepine 5,5-dioxides (PBTDs) induced apoptosis in
      human BCR-ABL-expressing leukemia cells. The apoptotic activity was also observed
      in primary leukemic blasts, obtained from chronic myelogenous leukemia (CML)
      patients at onset or from patients in blast crisis and who were imatinib
      resistant. Compounds 5 and 14 induced apoptosis before BCR-ABL protein expression
      and tyrosin phosphorylation were affected and activated different caspases in the
      apoptotic pathway. PBTDs are a new class of valid candidates for the treatment of
      CML.

PMID- 16970413
TI  - trans-Sodium crocetinate and diffusion enhancement.
AB  - trans-Sodium crocetinate (TSC) increases the diffusion coefficient of glucose
      through water by about 25-30%. This is the same percentage increase that TSC
      causes in the diffusivity of oxygen through water. TSC is also found to induce
      order in the surrounding water structure through increased hydrogen bonding of
      the water molecules, and molecular simulations suggest that the increase in
      diffusivity occurs only in these ordered regions.

PMID- 16970414
TI  - Assembly and electrochemical characterization of nanometer-scale electrode|solid
      electrolyte interfaces.
AB  - A technique is herein described for the assembly and characterization of
      nanometer-scale metal electrode|solid electrolyte interfaces of variable
      dimensions. The specific system examined in this work involves a sharp Pt tip
      attached to the piezo-driven head of a scanning tunneling microscope (STM)
      allowing the tip to be inserted into (or retrieved from) a Nafion membrane placed
      normal to the direction of tip travel. The actual Pt|Nafion area of contact was
      determined by coulometric analysis of the characteristic voltammetric features of
      Pt, using the tip as the working electrode and a much larger Pt gauze attached to
      the other side of the Nafion as a counter-reference electrode, yielding for some
      of the interfaces examined values equivalent to as low as 35 000 Pt surface
      atoms. This rather versatile arrangement allows experiments to be performed in
      both inert (Ar) and reactive atmospheres, such as oxygen or hydrogen on either or
      both sides of the membrane, under controlled humidity conditions, and thus sheds
      light into such phenomena as changes in the overall faradaic currents induced by
      plastic deformations of the Nafion as well as fundamental aspects of mass
      transport at reactant gas|Pt|Nafion three-boundary interfaces of relevance to
      polymer electrolyte fuel cells (PEFCs).

PMID- 16970415
TI  - Synthesis of niobia nanocrystals with controlled morphology.
AB  - In this work, TT niobia-phase nanocrystals with controlled morphology were
      obtained by the hydrothermal treatment of a niobium peroxo complex precursor at
      very low temperatures. The materials obtained by this route presented a very high
      surface area (ranging from 79 to 327 m(2)/g), disordered NbO(6), NbO(7), and
      NbO(8) polyhedra, Nb-O superficial sites, and a superficial OH group, which must
      have ensured the acidic characteristics of this oxide.

PMID- 16970416
TI  - Intermolecular interaction in TeO2 crystal.
AB  - It is shown that the abnormal long-range Te-Te intermolecular interaction in
      TeO(2) crystals may be related to the tunneling of electrons from the 5s(2)
      active lone pairs of Te(4+) ions and their partial delocalization on neighboring
      Te(4+).

PMID- 16970417
TI  - Probing electron transfer dynamics at MgO surfaces by Mg-atom desorption.
AB  - Ultraviolet excitation of high surface area MgO films using 4.7 eV femtosecond
      pulses results in neutral Mg-atom desorption with hyperthermal kinetic energies
      in the range 0.1-0.4 eV. The Mg-atom hyperthermal energies and power dependences
      are similar to those previously observed using nanosecond pulsed excitation.
      Femtosecond two-pulse correlation measurements reveal the existence of different
      dynamical paths for Mg-atom desorption. One mechanism displays a sub-150 fs time
      scale and involves the simultaneous or near-simultaneous transition of two
      electrons to a 3-coordinated Mg(2+) site. Other paths display picosecond time
      scales that we associate with dynamics following electron trapping at 3
      coordinated Mg(2+) surface sites.

PMID- 16970418
TI  - Femtosecond studies of tryptophan fluorescence dynamics in proteins: local
      solvation and electronic quenching.
AB  - We report our systematic examination of tryptophan fluorescence dynamics in
      proteins with femtosecond resolution. Distinct patterns of femtosecond-resolved
      fluorescence transients from the blue to the red side of emission have been
      characterized to distinguish local ultrafast solvation and electronic quenching.
      It is shown that tryptophan is an ideal local optical probe for hydration
      dynamics and protein-water interactions as well as an excellent local molecular
      reporter for ultrafast electron transfer in proteins, as demonstrated by a series
      of biological systems, here in melittin, human serum albumin, and human
      thioredoxin, and at lipid interfaces. These studies clarify the assignments in
      the literature about the ultrafast solvation or quenching dynamics of tryptophan
      in proteins. We also report a new observation of solvation dynamics at far red
      side emission when the relaxation of the local environment is slower than 1 ps.
      These results provide a molecular basis for using tryptophan as a local molecular
      probe for ultrafast protein dynamics in general.

PMID- 16970419
TI  - On the presence of Fe(IV) in Fe-ZSM-5 and FeSrO3-x --unequivocal detection of the
      3d4 spin system by resonant inelastic X-ray scattering.
AB  - The contribution of a 3d(4) spin configuration to the valence electronic
      structure of Fe compounds can be probed via spin-selective Fe K-pre-edge
      absorption spectra, using resonant inelastic X-ray scattering (RIXS). The 3d(4)
      configuration of Fe(IV) can be unequivocally detected even in a mixture with the
      high-spin 3d(5) configuration of Fe(III). This is demonstrated on the perovskite
      FeSrO(3-x) with formal oxidation state Fe(IV). When the technique was applied to
      an Fe-ZSM-5 catalyst during reaction with N(2)O, no 3d(4) configuration was
      detected. The formation of Fe(IV) upon reaction of Fe-ZSM-5 with N(2)O can,
      therefore, be ruled out.

PMID- 16970420
TI  - Growth and magnetic properties of oriented alpha-Fe2O3 nanorods.
AB  - alpha-Fe(2)O(3) nanorods have been deposited on Si substrates using the metal
      organic chemical vapor deposition method. Structural analyses indicated that
      alpha-Fe(2)O(3) nanorods are preferentially oriented in the [104] direction on
      Si(100) substrates, and the nanorod possesses the single-crystalline structure.
      MFM image suggests that a spin domain is formed in the alpha-Fe(2)O(3) nanorod.
      Anisotropic magnetic property of the alpha-Fe(2)O(3) nanorods, i.e., the
      discrepancy of the saturation magnetization, is observed from SQUID measurements
      when the magnetic field are applied parallel and perpendicular to the substrate.
      A lower Morin temperature than that of the macroscopically crystalline hematite
      is observed when the magnetic field is applied parallel to the substrate.

PMID- 16970421
TI  - Solvation and dynamic behavior of cyclodextrins in dimethyl sulfoxide solution.
AB  - High-frequency dielectric relaxation behavior up to 20 GHz was investigated for
      plain (alpha, beta, gamma) and (62 and 100%) methylated cyclodextrins, CDs, in
      dimethyl sulfoxide, DMSO, solution. Each hydrogen atom of OH groups of the CDs
      solvated a DMSO molecule for a residence time of 130-180 ps due to the hydrogen
      bond formation to an oxygen atom of DMSO, and a few DMSO molecules were included
      in cavities of the CDs for a while similar to the residence time. The overall
      rotational relaxation modes of solvated CDs were also observed depending on the
      effective sizes of the solvated CDs.

PMID- 16970422
TI  - First isolation of individual silicate platelets from clay exfoliation and their
      unique self-assembly into fibrous arrays.
AB  - Thin silicate platelets in a dimension of approximately 80 x 80 x 1 nm(3) are
      isolated for the first time by a newly developed process involving one-step
      exfoliation of natural montmorillonite clay and toluene/aqueous NaOH extraction.
      The platelets are observed to be polygon shape by transmission electron
      microscopy (TEM) and round bent-leaf shape by dynamic force microscopy (DFM).
      Individual platelets possessing high-aspect-ratio dimension and ionic character
      are able to self-assemble into microscale fiber bundles after water evaporation.
      The self-stacking mechanism indicated strong face-to-face ionic charge stacking
      propensity in triggering a vertical growth. Regularity of fibrous bundles in an
      average 5 microm length has been observed.

PMID- 16970423
TI  - Investigation of surface interactions in molecular recognition of phosphonate
      imprinted organosilicates and the role of water.
AB  - Surface interactions in molecular recognition of phosphonate imprinted
      organosilicates and the role of water have been studied. NMR and calorimetry
      studies have shown the changing nature of the surface water structure on silicate
      surfaces due to template directed molecular imprinting. Results indicate the
      interaction of an organophosphonate compound with the functionalized silica
      surfaces to be through surrounding water molecules. However, with
      nonfunctionalized surfaces, additional higher energy interactions were possible.
      Further, our results support the possible templating effect of water during the
      imprint process.

PMID- 16970424
TI  - Homogeneous freezing of water starts in the subsurface.
AB  - Molecular dynamics simulations of homogeneous ice nucleation in extended aqueous
      slabs show that freezing preferentially starts in the subsurface. The top surface
      layer remains disordered during the freezing process. The subsurface accommodates
      better than the bulk the increase of volume connected with freezing. It also
      experiences strong electric fields caused by oriented surface water molecules,
      which can enhance ice nucleation. Our computational results shed new light on the
      experimental controversy concerning the bulk vs surface origin of homogeneous ice
      nucleation in water droplets. This has important atmospheric implications for the
      microphysics of formation of high altitude clouds.

PMID- 16970425
TI  - Direct identification of conformational isomers of adsorbed oligothiophene on
      Cu100.
AB  - A direct conformational analysis using scanning tunneling microscopy (STM) has
      been performed for individual adsorbed alpha-octithiophene molecules on Cu(100).
      s-cis and s-trans conformational isomers are induced by the rotational
      flexibility of individual thiophene rings. By adding bulky N-silyl substituents
      to octithiophene, we successfully identify the s-cis and s-trans conformational
      isomers using STM. The obtained relative abundances of the s-cis and s-trans
      conformations are analyzed using ab initio molecular orbital calculations.

PMID- 16970426
TI  - Continuous self-avoiding walk with application to the description of polymer
      chains.
AB  - We develop the continuous self-avoiding walk (CSAW) methodology for investigating
      temperature dependent thermodynamic properties of finite polymer chains without
      imposing a lattice. This leads to a new concept: the free energy theta
      temperature, T(theta)(F), at which the free energy is proportional to chain
      length. Above T(theta)(F), the polymer chain-solvent mixture leads to a single
      phase, whereas below T(theta)(F) the polymer solvent system has a positive
      surface tension with a tendency to phase separation to form a globular phase. For
      finite chains this coil-globule transition lies above the geometric theta
      temperature at which the distribution describes a Gaussian coil. CSAW provides
      the basis for a new approach to predict globular properties of real polymers.

PMID- 16970427
TI  - Synthesis and electrical transport of single-crystal NH4V3O8 nanobelts.
AB  - Monoclinic NH(4)V(3)O(8) single-crystalline nanobelts with widths of 80-180 nm,
      thicknesses of 50-100 nm, and lengths up to tens of micrometers have been
      synthesized at large scale in an ammonium metavanadate solution by a
      templates/catalysts-free route. Such nanobelts grow along the direction of [010].
      The individual NH(4)V(3)O(8) nanobelt exhibits nonlinear, symmetric
      current/voltage (I/V) characteristics, with a conductivity of 0.1-1 S/cm at room
      temperature and a dielectric constant of approximately 130. The dominant
      conduction mechanism is based on small polaron hopping due to ohmic mechanism at
      low electric field below 249 V/cm due to Schottky emission at medium electric
      field between 249 and 600 V/cm and due to the Poole-Frenkel emission mechanism at
      high field above 600 V/cm.

PMID- 16970428
TI  - Metallic single-crystal CoSi nanowires via chemical vapor deposition of single
      source precursor.
AB  - We report the synthesis, structural characterization, and electrical transport
      properties of free-standing single-crystal CoSi nanowires synthesized via a
      single-source precursor route. Nanowires with diameters of 10-150 nm and lengths
      of greater than 10 mum were synthesized through the chemical vapor deposition of
      Co(SiCl(3))(CO)(4) onto silicon substrates that were covered with 1-2 nm thick
      SiO(2). Transmission electron microscopy confirms the single-crystal structure of
      the cubic CoSi. X-ray absorption and emission spectroscopy confirm the chemical
      identity and show the expected metallic nature of CoSi, which is further verified
      by room-temperature and low-temperature electrical transport measurements of
      nanowire devices. The average resistivity of CoSi nanowires is found to be about
      510 muOmega cm. Our general and rational nanowire synthesis approach will lead to
      a broad class of silicide nanowires, including those metallic materials that
      serve as high-quality building blocks for nanoelectronics and magnetic
      semiconducting Fe(1-x)Co(x)Si suitable for silicon-based spintronics.

PMID- 16970429
TI  - Quantitative link between single-particle dynamics and static structure of
      supercooled liquids.
AB  - We present evidence via molecular simulation that the supercooled fluid states of
      SPC/E water as well as the "repulsive" and "attractive" supercooled fluid states
      of a recently introduced model for colloids with short-ranged attractions are
      characterized by the same functional relationship between self-diffusivity and
      the pair correlation function. We discuss how this simple relationship connects
      to an earlier finding that the temperature dependency of a supercooled fluid's
      single-particle dynamics tracks that of its excess entropy (relative to ideal
      gas). The generality of this observed structure-property relationship is
      supported by its ability to successfully describe the nontrivial behaviors of
      these very different types of model systems.

PMID- 16970430
TI  - Probing surface-porphyrazine reduction potentials by molecular design.
AB  - This manuscript reports electrochemical and angle-resolved X-ray photoelectron
      spectroscopy measurements of surface-bound porphyrazine monolayers in which the
      molecule-surface distance and molecular orientation of the porphyrazine are
      controlled through the design of the adsorbates. This system has allowed us to
      probe the importance of molecule-surface interaction in determining the shift in
      reduction potential upon binding to a gold surface. This quantity currently is in
      theoretical dispute, with one computation indicating that a
      porphyrazine/porphyrin exhibits an extremely large covalent binding energy (
      approximately 10 eV) to a gold surface, whereas a more recent one finds the
      binding energy to be only a fraction of an electronvolt. Our study indicates that
      the shift in reduction potential upon surface binding is not a discontinuous
      function of the molecule-surface distance, as would be the case if covalent
      interaction of the porphyrazine core with the gold surface were controlling, but
      rather varies smoothly. This, therefore, rules out the possibility that the large
      potential shift seen for a porphyrazine whose macrocyclic core lies approximately
      3.9 A above the gold surface, relative to one that lies approximately 8.9 A above
      the surface, DeltaDeltaE = 340 mV, is caused by direct covalent binding of the pi
      system to the metal surface.

PMID- 16970431
TI  - Hierarchical self-assembly of silver nanocluster arrays on triblock copolymer
      templates.
AB  - Poly(styrene-b-butadiene-b-styrene) (SBS) triblock copolymer templates which
      present in-plane cylinders of polystyrene (PS) aligned parallel to the plane of
      the substrate have been prepared by a solvent-induced order-disorder phase
      transition method. Silver nanoclusters have been obliquely deposited onto the SBS
      copolymer templates at low coverage, utilizing the directed low-energy cluster
      beam deposition (LECBD) method. The morphology of the samples has been
      characterized by a tapping-mode AFM. It is shown that the silver nanoclusters
      form ordered linear arrays and the intercluster distance within each individual
      linear array is comparable to the cluster size. Optical absorption spectra
      indicate that the surface plasmon resonance (SPR) of the silver nanocluster
      linear arrays occurs at about 444.5 nm, manifesting a red shift of approximately
      21.4 nm compared to the SPR absorption of silver nanoclusters deposited on a
      fused quartz substrate. This is attributed mainly to the near-field
      electrodynamic interactions between the silver nanoclusters. This hierarchical
      approach to create ordered nanostructures transcends the spatial limits of
      lithography and provides a promising route to achieve well-ordered cluster-based
      nanostructures.

PMID- 16970432
TI  - Self-assembly in a catanionic mixture with an aminoacid-derived surfactant: from
      mixed micelles to spontaneous vesicles.
AB  - The aqueous self-assembly of a novel lysine-derived surfactant with a gemini-like
      architecture, designated here as 12-Lys-12, has been experimentally investigated
      for the amphiphile alone in water and in a mixture with dodecyltrimethylammonium
      bromide (DTAB). The neat surfactant forms interesting micrometer-sized rigid
      tubules in the dilute region, resulting in very viscous solutions. For the
      catanionic mixture with DTAB, various single and multiphase regions were
      identified (up to a total surfactant concentration of 1.5 wt %) by means of
      combined polarizing light microscopy, cryo-TEM, and NMR. In the DTAB-rich side,
      for a mixing molar ratio in the range 2 < DTAB/12-Lys-12 < 4, a region of stable,
      unilamellar vesicles can be found. Furthermore, it was found that upon addition
      of 12-Lys-12 to pure DTAB solutions, the mixed micelles grow and beyond a given
      mixing ratio, vesicles assemble and coexist with small micelles. The transition
      is not continuous, since there is a narrow mixing range where phase separation
      occurs. Self-diffusion measurements and cryo-TEM imaging show that the average
      vesicle radius is on the order of 30-40 nm.

PMID- 16970433
TI  - Electron-phonon interactions and intra- and intermolecular charge mobility in the
      monocations of annulenes.
AB  - Possible electron pairing in pi-conjugated positively charged annulenes such as
      (CH)(18) (18an) and (CH)(30) (30an) is studied and compared with that in the
      positively charged acenes. The total electron-phonon coupling constants in the
      monocations (l(HOMO)) for 18an and 30an are estimated. The E(2g) modes of 1611
      and 1201 cm(-1) most strongly couple to the highest occupied molecular orbitals
      (HOMO) in 18an and 30an, respectively. The l(HOMO) values for annulenes are
      larger than those for acenes. The phase pattern difference between the HOMO of
      acenes localized on the edge part of carbon atoms and the delocalized HOMO of
      annulenes is the main reason for the calculated results. In view of the
      calculated results of the l(HOMO) values, intramolecular electron mobility
      (sigma(intra,HOMO)), and the reorganization energies (RE(HOMO)) in the positively
      charged molecules, the monocations of annulenes cannot easily become good
      conductors compared with the monocations of acenes, but the condition of the
      attractive electron-electron interactions is realized more easily in the
      monocations of annulenes than in the monocations of acenes. The hypothetical
      intramolecular supercurrent originating from both intramolecular and
      intermolecular vibrations in the monocations of annulenes and acenes in a case
      where the distance between two adjacent molecules is too large for the molecular
      crystal to become normal metallic state, is also discussed.

PMID- 16970434
TI  - Experimental and theoretical investigation of the electronic structure of 5
      fluorouracil compounds.
AB  - We present a comparison between experimental and theoretical X-ray absorption
      spectroscopy (XAS) and X-ray emission spectroscopy (XES) of 5-fluorouracil
      compounds, with an emphasis on the effects of the inclusion of nickel in the
      structure. By focusing on the 1s thresholds of carbon, nitrogen, oxygen, and
      fluorine it was possible to provide a complete picture of the occupied and
      unoccupied partial density of states of the 5-fluorouracil systems. Spectra
      calculated using density functional theory are compared to experimental results.
      Most experimental results agree well with our theoretical calculations for the
      XAS and XES of the compounds. All spectral features are assigned. Our results
      reveal that the nickel in the compound is coordinated with the nitrogen sites of
      the 5-fluorouracil ligands.

PMID- 16970435
TI  - Novel route to WOx nanorods and WS2 nanotubes from WS2 inorganic fullerenes.
AB  - WO(x) (2 < x < 3) and WS(2) nanostructures have been widely praised due to
      applications as catalysts, solid lubricants, field emitters, and optical
      components. Many methods have been developed to fabricate these nanomaterials;
      however, most attention was focused on the same dimensional transformation from
      WO(x) nanoparticles or nanorods to WS(2) nanoparticles or nanotubes. In a solid
      vapor reaction, by simply controlling the quantity of water vapor and reaction
      temperature, we have realized the transformation from quasi-zero-dimensional
      WS(2) nanoparticles to one-dimensional W(18)O(49) nanorods, and subsequent
      sulfuration reactions have further converted these W(18)O(49) nanorods into WS(2)
      nanotubes. The reaction temperature, quantity of water vapor, and pretreatment of
      the WS(2) nanoparticle precursors are important process parameters for long,
      thin, and homogeneous W(18)O(49) nanorods growth. The morphologies, crystal
      structures, and circling transformation mechanisms of sulfide-oxide-sulfide are
      discussed, and the photoluminescence properties of the resulting nanorods are
      investigated using a Xe lamp under an excitation of 270 nm.

PMID- 16970436
TI  - Ab initio study of energetic solids: cupric azide, mercuric azide, and lead
      azide.
AB  - We presented a detailed study on the electronic structure and optical properties
      of cupric azide (Cu(N(3))(2)), mercuric azide (alpha-Hg(N(3))(2)), and lead azide
      (alpha-Pb(N(3))(2)) by using density functional theory within the generalized
      gradient approximation. Relaxed crystal structures compare well with experimental
      data. An analysis of electronic structure, charge transfer, and bond order shows
      that Cu(N(3))(2) and alpha-Hg(N(3))(2) are covalent-type solids, whereas alpha
      Pb(N(3))(2) is an ionic-type solid but has weak covalent character. The valence
      bands of Cu(N(3))(2) and alpha-Hg(N(3))(2) arise from the contributions of the
      metal-d and N-p states, whereas that of alpha-Pb(N(3))(2) are strongly dominated
      by N-p states and not from Pb-d states. The general shapes of the real and
      imaginary parts of the dielectric function, adsorption coefficient, and
      photoconductivity spectra for the three azides are similar. Our calculated
      optical properties are found to be in agreement with available experimental data.
      The absorption spectra show a number of absorption peaks in the fundamental
      absorption region. All the photoconductivity spectra display a broad photocurrent
      response in the fundamental absorption region. The density of states of the three
      azides reveal the effects of the metal states on the valence electron of the
      azide group and so are correlated with their impact sensitivity.

PMID- 16970437
TI  - Molecular dynamics simulations of PAMAM dendrimer-induced pore formation in DPPC
      bilayers with a coarse-grained model.
AB  - We have performed 0.5-micros-long molecular dynamics (MD) simulations of 0%, 50%,
      and 100% acetylated third- (G3) and fifth-generation (G5) polyamidoamine (PAMAM)
      dendrimers in dipalmitoylphosphatidylcholine (DPPC) bilayers with explicit water
      using the coarse-grained (CG) model developed by Marrink et al. (J.Phys. Chem. B
      2004, 108, 750-760), but with long-range electrostatic interactions included.
      Radii of gyration of the CG G5 dendrimers are 1.99-2.32 nm, close to those
      measured in the experiments by Prosa et al. (J. Polym. Sci. 1997, 35, 2913-2924)
      and atomistic simulations by Lee et al. (J. Phys. Chem. B 2006, 110, 4014-4019).
      Starting with the dendrimer initially positioned near the bilayer, we find that
      positively charged un-acetylated G3 and 50%-acetylated and un-acetylated G5
      dendrimers insert themselves into the bilayer, and only un-acetylated G5
      dendrimer induces hole formation at 310 K, but not at 277 K, which agrees
      qualitatively with experimental observations of Hong et al. (Bioconj. Chem. 2004,
      15, 774-782) and Mecke et al. (Langmuir 2005, 21, 10348-10354). At higher salt
      concentration (approximately 500 mM NaCl), un-acetylated G5 dendrimer does not
      insert into the bilayer. The results suggest that with inclusion of long-range
      electrostatic interactions into coarse-grained models, realistic MD simulation of
      membrane-disrupting effects of nanoparticles at the microsecond time scale is now
      possible.

PMID- 16970438
TI  - Monte Carlo simulations of cylinder-forming ABC triblock terpolymer thin films.
AB  - We systematically study the cylinder-forming ABC triblock terpolymer thin films
      using canonical ensemble Monte Carlo simulations. The simulated annealing
      procedure is applied to the self-assembling process. By judicious choice of the
      system dimensions, we elaborately investigate the effect of film thickness on the
      orientation of the cylinders. This confined triblock terpolymer system exhibits
      different phase behavior under the weak and strong surface fields. In addition,
      we also investigate the ensemble-averaged chain orientations and relative density
      profiles.

PMID- 16970439
TI  - A simple solution route to single-crystalline Sb2O3 nanowires with rectangular
      cross sections.
AB  - We report a simple solution route to large-scale synthesis of uniform, single
      crystalline, and well-faceted orthorhombic antimony trioxide (Sb(2)O(3))
      nanowires with rectangular cross sections by direct air oxidation of bulk metal
      antimony (Sb) in a mixed solution made of ethylenediamine (EDA) and deionized
      water (DIW). The as-synthesized products were analyzed by range of methods, such
      as XRD, SEM, EDX, TEM, SAED, HRTEM, FTIR, Raman, UV-vis absorption, and
      photoluminescence (PL) spectra. The as-synthesized Sb(2)O(3) nanowires with
      rectangular cross sections are usually hundreds of micrometers in length,
      typically 80-100 nm in width, and 60-80 nm in thickness. The novel room
      temperature photoluminescence properties of Sb(2)O(3) nanowires with rectangular
      cross sections displayed a significant UV luminescence with a strong emission
      band at 374 nm, which was reported for the first time, indicating the as
      synthesized products with an optical band gap E(g) = 3.3 eV. It is expected that
      as-synthesized Sb(2)O(3) nanowires would be a new member of functional materials
      and used in the manufacture of advanced nanodevices.

PMID- 16970440
TI  - Electrical bistability in electrostatic assemblies of CdSe nanoparticles.
AB  - We report electrical bistability in electrostatic assembly of CdSe nanoparticles.
      We obtained thin films of the nanoparticles via layer-by-layer electrostatic
      assembly technique, which provided a nanoscale control to tune the thickness.
      Devices based on such thin films exhibit electrical bistability along with memory
      phenomenon. The bistability is due to charge confinement in the nanoparticles.
      Conduction mechanism changes from an injection-dominated to a bulk one during
      switching from a low- to a high-conducting state. Additionally, results from
      impedance spectroscopy show that the dielectric constant of the material
      increases during the transition. Both random-access and read-only memory
      applications are observed in these systems.

PMID- 16970441
TI  - ZnO multipods, submicron wires, and spherical structures and their unique field
      emission behavior.
AB  - A simple method of vapor deposition for the shape selective synthesis of ZnO
      structures, namely, multipods, submicron wires, and spheres, has been
      successfully demonstrated. A plausible growth mechanism based on the studies of
      scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray
      diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) is proposed. Our
      studies suggest that the growth of a multipod structure is governed by the screw
      dislocation propagation while the vapor-liquid-solid (VLS) mechanism is
      responsible for the formation of submicron wires and spheres. Moreover, the flow
      rate of the carrier gas plays a crucial role in governing the morphology.
      Further, these structures exhibit an enhanced field emission behavior. The
      nonlinearity in the Fowler-Nordheim (F-N) plot, a characteristic feature of
      electron emission from semiconductors, is explained by considering the
      contributions from both the conduction and the valence bands of ZnO.

PMID- 16970442
TI  - Plasmon coupling in nanorod assemblies: optical absorption, discrete dipole
      approximation simulation, and exciton-coupling model.
AB  - The shape anisotropy of nanorods gives rise to two distinct orientational modes
      by which nanorods can be assembled, i.e., end-to-end and side-by-side, analogous
      to the well-known H and J aggregation in organic chromophores. Optical absorption
      spectra of gold nanorods have earlier been observed to show a red-shift of the
      longitudinal plasmon band for the end-to-end linkage of nanorods, resulting from
      the plasmon coupling between neighboring nanoparticles, similar to the assembly
      of gold nanospheres. We observe, however, that side-by-side linkage of nanorods
      in solution shows a blue-shift of the longitudinal plasmon band and a red-shift
      of the transverse plasmon band. Optical spectra calculated using the discrete
      dipole approximation method were used to simulate plasmon coupling in assembled
      nanorod dimers. The longitudinal plasmon band is found to shift to lower energies
      for end-to-end assembly, but a shift to higher energies is found for the side-by
      side orientation, in agreement with the optical absorption experiments. The
      strength of plasmon coupling was seen to increase with decreasing internanorod
      distance and an increase in the number of interacting nanorods. For both side-by
      side and end-to-end assemblies, the strength of the longitudinal plasmon coupling
      increases with increasing nanorod aspect ratio as a result of the increasing
      dipole moment of the longitudinal plasmon. For both the side-by-side and end-to
      end orientation, the simulation of a dimer of nanorods having dissimilar aspect
      ratios showed a longitudinal plasmon resonance with both a blue-shifted and a red
      shifted component, as a result of symmetry breaking. A similar result is observed
      for a pair of similar aspect ratio nanorods assembled in a nonparallel
      orientation. The internanorod plasmon coupling scheme concluded from the
      experimental results and simulations is found to be qualitatively consistent with
      the molecular exciton coupling theory, which has been used to describe the
      optical spectra of H and J aggregates of organic molecules. The coupled nanorod
      plasmons are also suggested to be electromagnetic analogues of molecular
      orbitals. Investigation of the plasmon coupling in assembled nanorods is
      important for the characterization of optical excitations and plasmon propagation
      in these nanostructures. The surface plasmon resonance shift resulting from
      nanorod assembly also offers a promising alternative for analyte-sensing assays.

PMID- 16970443
TI  - Structure and dynamics of hydrogen bonds in the interface of a C12E6 spherical
      micelle in water solution: a MD study at various temperatures.
AB  - The temperature dehydration of a C(12)E(6) spherical micelle is characterized
      through the study of the structure and dynamics of the hydrogen bonds formed by
      water within the micellar interface. Water molecules in proximity of the
      hydrophilic fragment of the C(12)E(6) surfactants form strong H-bonds with the
      oxyethilene units E and with the polar alcoholic heads. The activation energies
      of such H-bonds fall in the range 2-3 Kcal mol(-1). On the exposed oil core, the
      number of water-water H-bonds decreases as an effect of dehydration. The dynamics
      of such bonds exhibits a slow relaxation with respect to the bulk, and two time
      scales can be discerned: the first one, tau approximately 3-6 ps, is typical of
      water-water H-bonds around small hydrophobic molecules, whereas the second one,
      tau approximately 40-80 ps, is probably due to the confining effect of the long
      hydrophilic fragments which reduces the probability of a water molecule to leave
      the hydration layer of the exposed oil core. Water molecules around the core form
      H-bond clusters whose size and distribution change with temperature. From a
      cluster analysis, the system appears to be below the percolation threshold,
      suggesting that the exposed oily surface is formed by disconnected patches of
      size around 1 nm(2), close to the estimate of the solvated hydrophobic patches on
      protein surfaces. The network connectivity is also considered for concentric
      hydration shells along the interface: it turns out that near the oil core, the
      cluster size is larger than elsewhere in the interface demonstrating a strong
      structural effect induced by the exposed hydrocarbon tails. Temperature affects
      the cluster size only in the innermost shell.

PMID- 16970444
TI  - Synthesis and Photoluminescence of Cd-doped alpha-MnS Nanowires.
AB  - Cd-doped alpha-MnS nanowires (av diam = 70 nm) were synthesized by the chemical
      vapor deposition of MnCl(2)/CdS powders. They all consisted of single-crystalline
      rock-salt MnS structures with the [111] growth direction. The X-ray diffraction
      pattern analysis indicates that 10% Cd doping would expand the lattice constants
      by 0.3%. As the content of Cd increases, the band edge emission band (2.9 eV) of
      photoluminescence becomes broader, and the Mn(2+) emission band (1.6 eV), which
      emerged at temperatures below approximately 150 K, decreases in intensity. The
      decay time of the 1.6 eV band decreases from 40 to 30 mus when the Cd doping is
      increased from 0 to 10%. In contrast to the bulk (T(N) = 150 K), the MnS
      nanowires were found to be paramagnetic with antiferromagnetic interactions.
      These distinctive magnetic properties of the nanowires have a strong correlation
      with their photoluminescence, which could be influenced by the nanosize effect
      and the Cd doping.

PMID- 16970445
TI  - Boron-doped carbon nanotubes serving as a novel chemical sensor for formaldehyde.
AB  - To search for a novel sensor to detect the presence of formaldehyde (HCOH), we
      investigate reactivities of the intrinsic and boron-doped (B-doped) single-walled
      (8, 0) carbon nanotube (SWCNT) with HCOH using density functional theory
      calculations. Compared with the intrinsic SWCNT, the B-doped SWCNT presents high
      sensitivity to HCOH. This is attributed to the strongly chemical interaction
      between the electron-rich oxygen atom of HCOH and the electron-scarce boron atom
      of the doped SWCNT. B-doped SWCNTs are expected to be a potential candidate for
      detecting the presence of HCOH.

PMID- 16970446
TI  - Structural isomers and reactivity for Rh6 and Rh6+.
AB  - The structure, energetics, and interconversion of isomers of Rh(6) and Rh(6)(+)
      are studied by using density functional theory with Gaussian basis sets, using
      guess structures derived from basin-hopping simulations, and obtained by using
      the Sutton-Chen potential. A large range of spin multiplicities is considered for
      each isomer. Our calculations suggest two low-lying structures as possible
      structural isomers: a square bipyramid and a trigonal prism. The reactivity of
      these two candidate structural isomers with respect to adsorption of nitric oxide
      is studied via location of reaction transition states and calculation of reaction
      barriers. Similarities and differences with surface reaction studies are
      highlighted. These data provide powerful evidence that structural isomerism, and
      not different spin states, is responsible for the observed biexponential reaction
      kinetics.

PMID- 16970447
TI  - Nanoscale heterogeneity in ceria zirconia with low-temperature redox properties.
AB  - We have investigated nanoscale compositional and structural variations in
      Ce(0.5)Zr(0.5)O(2) samples with different redox properties. Different samples
      were prepared using a spray freezing technique, and the synthesis conditions were
      varied to yield materials with reduction temperatures in the range of 400-750
      degrees C. X-ray diffraction and thermal gravimetric analysis were used to
      characterize the average structures and redox properties of these materials. The
      nanoscale structural and compositional variations in individual nanoparticles of
      high activity were determined with atomic-scale electron imaging and nanometer
      resolution electron energy loss spectroscopy. During the early stage of particle
      formation, the crystallization process is initiated via the nucleation of ceria
      rich nanodomains. This results in the formation of high-surface-area materials
      that exhibit nanoscale compositional heterogeneity consisting of Ce-rich cores
      surrounded by Zr-rich shells. The effect of high-temperature redox cycling on the
      nanoscale structure, composition, and low-temperature redox properties was also
      determined. Our analysis suggests that our most active material exhibits
      significant compositional and structural heterogeneity at the nanometer level.

PMID- 16970448
TI  - Charge accumulation and polarization in titanium dioxide electrodes.
AB  - Nanocrystalline TiO(2) electrodes were studied spectroelectrochemically by
      observing the simultaneous relaxation of the current and absorbance after
      applying a voltage step. The absorbance behaved differently in two time regimes:
      (1) ionic polarization in the oxide electrode, in which charged ions, such as
      Ti(3+) sites and/or interstitial Ti(4+) sites, move in response to the applied
      electric field, and (2) the diffusion of Li(+) ions into the TiO(2). These two
      behaviors were analyzed with equivalent circuit models. Li(+) ions reduce the
      resistance of the TiO(2) by approximately 90%, increase the capacitance by
      approximately 350%, and decrease the inductance by approximately 30%. Voltage
      cycling produces a buildup of intercalated Li(+) ions, lessening the electrode's
      response to the potential step, and causing it to become a more efficient
      inductor. The potential distribution in the nanoparticles is described by using a
      dielectric model in which roughly half the applied potential is dropped across
      the interface with a Li(+)-ion-containing electrolyte.

PMID- 16970449
TI  - Formation of silver nanoparticles in deoxyribonucleic acid-poly(o-methoxyaniline)
      hybrid: a novel nano-biocomposite.
AB  - A novel nano-biocomposite of silver and poly(o-methoxy aniline) (POMA)/DNA hybrid
      has been prepared by adding DNA solution to an aqueous solution of POMA
      (emeraldine base, EB) and AgNO(3) mixture. The mixture was aged for 10 days and
      was freeze-dried to form the hybrid nanocomposite (weight fraction of DNA =
      0.75). FESEM pictures show a fibrillar network morphology of the biomolecular
      hybrid with silver nanoparticles on its surface. The TEM picture also
      corroborates silver nanoparticle formation in the biomolecular hybrid, and the
      denser population of nanoparticles in the TEM micrograph as compared to that in
      the SEM micrograph indicates that the nanoparticles are present inside the
      fibrils in greater proportion. The dc conductivity value of the hybrid indicates
      that POMA (EB) is doped by silver ion and the doped POMA form complexes with DNA
      through electrostatic interaction of the radical cation of POMA (emeraldine salt
      form, ES) and the DNA anion. During the doping process and Ag nanoparticle
      formation, a fluctuation of the pi band to polaron band transition peak occurs
      together with a complementary fluctuation of the polaron band to pi* band
      transition peak. After 53 h of aging, the former shows a slow but continuous red
      shift with aging time. This has been attributed to the slow uncoiling of POMA on
      the DNA surface. The conformation and crystal structure of DNA remain intact
      during the nano-biocomposite formation. The dc conductivity value of the nano
      biocomposite is almost the same as that of the pure POMA-DNA hybrid at the same
      composition, but the I-V characteristic curve of the nano-biocomposite is
      somewhat different showing an insulating region on low applied voltage. At higher
      applied voltage, it shows a semiconducting property characterizing the large band
      gap semiconducting behavior of the nano-biocomposite.

PMID- 16970450
TI  - Characteristics of carbon nanoparticles synthesized by a submerged arc in
      alcohols, alkanes, and aromatics.
AB  - Fullerene-related carbon nanostructures can be synthesized by an arc-in-liquid
      system as a cost-effective technique. In this work, we investigated the effects
      of additional carbon sources from liquid media that were alcohols (C(m)H(2m+1)OH,
      m = 1-8), alkanes (C(m)H(2m+2), m = 6-7), and aromatic compounds (C6H6-C(n)H(2n),
      n = 1-2) on the product structures and the yield of nanocarbon-rich deposits. It
      was found that carbon nanoparticles (CNPs) that included multi-walled carbon
      nanotubes (MW-CNTs) and multi-shelled carbon nanoparticles were produced at high
      concentrations in the hard deposit at the cathode tip formed by the arc in the
      alcohols and alkanes, similar to that in a water environment. Importantly, not
      only graphite electrodes but also these organic compounds played a role of a
      carbon source to produce CNPs that led to an approximately 8-100 times higher
      yield than the arc-in-water system. There was a tendency that the increase in
      alcohol concentration and carbon content in the organic molecules positively
      affected the yield and production rate of the CNPs. However, the selectivity of
      MW-CNTs was significantly reduced when aromatic compounds were used. Structural
      analyses by dynamic light scattering and Raman spectroscopy revealed the
      dependency of the hydrodynamic particle sizes of CNPs and their crystallinity on
      the liquid components. For a discussion on the reaction mechanism, optical
      emission spectra of the arc plasma were analyzed to estimate the arc temperature.
      In addition, liquid byproducts were analyzed by a UV-vis absorbance spectrometer.

PMID- 16970451
TI  - Indications for a surface temperature excess in heterogeneous catalysis.
AB  - We explored the surface temperature excess DeltaT = T(r) - T(m) (real reaction
      temperature T(r), measured catalyst temperature T(m)) on the basis of
      experimental data, a gradually curved Arrhenius plot for CO oxidation reactions
      over Pd/gamma-Al(2)O(3) catalysts. Such a plot could be an indication of the
      surface temperature excess in the 2-dimensional reaction surfaces of catalysts.
      The positive or negative surface temperature excess could be developed to be a
      general explanation for a gradually curved Arrhenius plot of a gas-solid
      catalytic system. This is a new insight into solving the puzzle on such common
      phenomena in heterogeneous catalysis. By using the reciprocal of the real
      reaction temperature T(r) in the hypothetical 2-D reaction surface, instead of
      the experimentally determined catalyst temperature T(m) or the gas temperature
      T(g), the gradually curved Arrhenius plot becomes linear. We investigated the
      implications of such a difference among T(r), T(m), and T(g). The surface
      temperature excess could be the effect of coupling between the fluxes of a
      chemical reaction and heat transport in the 2-D reaction surface. Its order of
      magnitude is 10 K for the present model system.(1) The surface temperature excess
      increases exponentially with the reaction temperature.

PMID- 16970452
TI  - Cell model of the direct current electrokinetics in salt-free concentrated
      suspensions: the role of boundary conditions.
AB  - In this paper, a general electrokinetic theory for concentrated suspensions in
      salt-free media is derived. Our model predicts the electrical conductivity and
      the electrophoretic mobility of spherical particles in salt-free suspensions for
      arbitrary conditions regarding particle charge, volume fraction, counterion
      properties, and overlapping of double layers of adjacent particles. For brevity,
      hydrolysis effects and parasitic effects from dissolved carbon dioxide, which are
      present to some extent in more "realistic" salt-free suspensions, will not be
      addressed in this paper. These issues will be analyzed in a forthcoming
      extension. However, previous models are revised, and different sets of boundary
      conditions, frequently found in the literature, are extensively analyzed. Our
      results confirm the so-called counterion condensation effect and clearly display
      its influence on electrokinetic properties such as electrical conductivity and
      electrophoretic mobility for different theoretical conditions. We show that the
      electrophoretic mobility increases as particle charge increases for a given
      particle volume fraction until the charge region where counterion condensation
      takes place is attained, for the above-mentioned sets of boundary conditions.
      However, it decreases as particle volume fraction increases for a given particle
      charge. Instead, the electrical conductivity always increases with either
      particle charge for fixed particle volume fraction or volume fraction for fixed
      particle charge, whatever the set of boundary conditions previously referred. In
      addition, the influence of the electric permittivity of the particles on their
      electrokinetic properties in salt-free media is examined for those frames of
      boundary conditions.

PMID- 16970453
TI  - Method of rapid assessment of photocatalytic activities of self-cleaning films.
AB  - An ink, comprising the redox dye resazurin (Rz) and the sacrificial electron
      donor glycerol, is shown to be capable of the rapid assessment of the
      photocatalytic activities of self-cleaning films. In the key initial stage of
      photocatalysis the ink changes from blue to pink. Prolonged irradiation bleaches
      the ink and eventually mineralizes it. The kinetics of the initial photoinduced
      color change is studied as a function of UV irradiance, [glycerol], [Rz], and
      temperature. The results reveal an apparent approximate quantum yield of 3.5 x
      10(-3) and an initial rate, r(i), which increases with [glycerol] and decreases
      with [Rz]. It is proposed that the reduction of Rz, dispersed throughout the
      thick (ca. 590 nm) indicator film, may take place either via the diffusion of the
      dye molecules in the ink film to the surface of the underlying semiconductor
      layer and their subsequent reaction with photogenerated electrons and/or via the
      diffusion of alpha-hydroxyalkyl radicals, produced by the oxidation of the
      glycerol by photogenerated holes, or hydroxy radicals, away from the surface of
      the semiconductor into the ink film and their subsequent reaction with the dye
      molecules therein. The decrease in r(i) with [Rz] appears to be due to dimer
      formation, with the latter impeding the reduction process. The activation energy
      for the initial color-change process is low, ca. 9.1 +/- 0.1 kJ mol(-1) and not
      unlike many other photocatalytic processes. The initial rate of dye reduction
      appears to be directly related to the rate of destruction of stearic acid. The
      ink can be applied by spin-coating, stamping, or writing, using a felt-tip pen.
      The efficacy of such an ink for assessing the photocatalytic activity of any
      photocatalytic film, including those employed on commercial self-cleaning
      glasses, tiles, and paving stones, is discussed briefly.

PMID- 16970454
TI  - Anisotropic and passivation-dependent quantum confinement effects in germanium
      nanowires: a comparison with silicon nanowires.
AB  - Electronic structures of hydrogen-passivated germanium nanowires (GeNWs) along
      the [100], [110], [111], and [112] directions are studied by using the density
      functional theory within the generalized gradient approximation. The band gaps of
      the fully relaxed GeNWs along the [100], [110], and [111] directions are all
      direct at the smaller sizes, while those of the wires along the [112] direction
      remain indirect. The magnitude of the band gaps of the GeNWs for a given size
      approximately follows the order of E(g)[100] > E(g)[111] > E(g)[112] > E(g)[110].
      Compared with silicon nanowires, GeNWs exhibit stronger quantum confinement
      effects. Replacement of H by the more stable ethine group is found to lead to a
      weakening of the quantum confinement effects of GeNWs.

PMID- 16970455
TI  - Cooperative hydrogen bonds of macromolecules. 2. Two-dimensional cooperativity in
      the binding of poly(4-vinylpyridine) to poly(4-vinylphenol).
AB  - The hydrogen bond interaction of poly(4-vinylphenol) (PVF), ligated by a 20
      mol/mol excess of pyridine-d(5) (PD) in tetrahydrofuran-d(8), with poly(4
      vinylpyridine) (PVP) was studied using liquid and solid-state NMR and quantum
      mechanical calculations. Because of its cooperative interaction, PVP substitutes
      PD in its hydrogen bond with PVF, thus forming a PVF-PVP complex, which gradually
      precipitates from solution. On the basis of the 1H/13C NMR spin-diffusion
      experiments and density functional theory quantum calculations, the complex is
      shown to have the fairly regular structure of a polymer sheet with intermittent H
      bond links between PVF and PVP chains. The cooperativity of PVP interaction with
      PVF was studied by measuring the dependence of the binding degree alpha of PVP on
      its polymerization degree (P(n), being 10, 17, 30, 36, 48, 65, and 84) at various
      PVP/PVF molar ratios. The value of alpha was established indirectly by measuring
      the fraction of liberated PD using its 2H quadrupolar relaxation and pulsed field
      gradient spin-echo measurement of self-diffusion. The cooperativity is shown to
      be of a higher order and two-dimensional, that is, dependent on both the
      polymerization degree of PVP and its ratio to PVF. A mathematical model of such
      two-dimensional cooperativity based chiefly on a proximity effect is suggested.

PMID- 16970456
TI  - Fast ring-shape self-assembling in water-based ink-jetted droplets.
AB  - We report on a phenomenon of ring pattern formation of nanoparticles in small ink
      jetted droplets (30-60 microm diameter) of water-based suspensions on substrate,
      which occurs in several seconds, unlike 10 min and more in most previous works.
      The phenomenon may open the way for new applications connected with rapid
      creation of desired structures. In addition, we report here a method for the
      study of the relative motion of the solvent and pigments in suspension droplets
      by coloring the solvent with soluble dye and using spectral imaging techniques.

PMID- 16970457
TI  - Rationalization of nanowire synthesis using low-melting point metals.
AB  - In this paper, we provide a theoretical basis using thermodynamic stability
      analysis for explaining the spontaneous nucleation and growth of a high density
      of 1-D structures of a variety of materials from low-melting metals such as Ga,
      In, or Sn. The thermodynamic stability analysis provides a theoretical estimate
      of the extent of supersaturation of solute species in molten metal solvent. Using
      the extent of maximum supersaturation, the size and density of critical nucleus
      were estimated and compared with experimental results using nucleation and growth
      of Ge nanowires using Ga droplets. The consistency of the proposed model is
      validated with the size and density of the resulting nanowires as a function of
      the synthesis temperature and droplet size. Both the experimental evidence and
      the theoretical model predictions point that the diameters of the resulting
      nanowires decrease with the lowering of synthesis temperatures and that the
      nucleation density decreases with the size of metal droplet diameter and
      increasing synthesis temperature.

PMID- 16970458
TI  - Viscosity measurements of water at high temperatures and pressures using dynamic
      light scattering.
AB  - The application of dynamic light scattering to measure viscosity of water at high
      temperatures and pressures is demonstrated. Viscosity was obtained from the
      translational diffusion coefficient of probe particles dispersed in the medium by
      the Einstein-Stokes relationship. Measurements were carried out with polystyrene
      latex, colloidal silica, and colloidal gold. Under a constant pressure of 25 MPa,
      good agreement was found between the measured and calculated viscosities up to
      275 degrees C with the polystyrene latex, 200 degrees C with the colloidal
      silica, and 297 degrees C with the colloidal gold. It was found that failure of
      the measurements at high temperatures is ascribed to change in either the
      dispersion stability or chemical stability of the probe particles. The present
      results indicate that the technique could also be used for other supercritical
      fluids having high critical temperature and pressure, such as methanol (T(c) =
      239.4 degrees C, P(c) = 8.1 MPa) and ethanol (T(c) = 243.1 degrees C, P(c) = 6.4
      MPa).

PMID- 16970459
TI  - Dissociative adsorption of carbon monoxide on Mo(110): first-principles theory.
AB  - The adsorption and dissociation of carbon monoxide on Mo (110) surface is studied
      with density functional theory. The results at different sites (atop, short
      bridge, long bridge, and hollow) are presented. The hollow site is found to be
      the most stable adsorption site for CO. The CO molecule is found to adsorb in end
      on configurations (alpha states) at high coverage and inclined configurations
      (beta states) at low coverage. The dissociation activation energy from beta
      states is found to be approximately 1 eV lower than from alpha state. The
      adsorption of dissociation products, C and O, on Mo(110) has also been studied.
      The most stable adsorption site for C and O is long bridge and hollow site,
      respectively. The adsorption of C and O at low coverage is, in general, stronger
      than at high coverage, which is partly responsible for the high reactivity of CO
      dissociation at low coverage, since the binding energy of CO is not very
      sensitive to the coverage.

PMID- 16970460
TI  - Neopentane and solid acids: direct hydron exchange before cracking.
AB  - The hydrogen/deuterium exchange reaction of 2,2-dimethylpropane (neopentane) over
      D(2)O-exchanged zeolites (MOR, FAU, BEA, MFI) using a batch recirculation reactor
      was studied by means of gas chromatography coupled with mass spectrometer. In the
      temperature range 473-573 K, H/D exchange proceeds without side reaction such as
      cracking at short contact times. Indeed the C-H bond has appeared favorably
      involved in the activation of neopentane compared to the less accessible C-C
      bond. The transition state allowing hydron exchange is most likely a carbonium
      species (pentacoordinated carbon) as in the case of the H/D exchange between
      methane and solid acid. The activation energies of the H/D exchange between
      neopentane and zeolites are the same for all zeolites indicating a common
      carbonium ion type transition state. On the basis of previous results in the case
      of the exchange between methane and liquid superacids, the deuterium exchange
      rates in neopentane were tentatively related to the acidity of the solids.
      However the order of activity MOR > MFI > BEA > FAU seems to be related to the
      size of the pores, which may suggest the involvement of a confinement effect in
      the zeolites cavities. Moreover we found that H/D exchange takes also place
      between neopentane and deuterated sulfated zirconia (SZ) emphasizing its strong
      acidity.

PMID- 16970461
TI  - Oxygen reduction reaction catalysts prepared from acetonitrile pyrolysis over
      alumina-supported metal particles.
AB  - Noble-metal-free active catalysts for the oxygen reduction reaction (ORR) in an
      acidic environment were prepared from the pyrolysis of acetonitrile at 900
      degrees C over alumina and metal-doped alumina. This work includes analyses of
      the nitrogen-doped carbon preparation process, characterization of the carbon
      materials formed, and activity testing for the ORR. The nitrogen-containing
      carbon nanostructures that formed during the pyrolysis of acetonitrile could be
      purified by washing the product with hydrofluoric acid. A wide range of
      techniques were used to characterize the solid carbon products of the
      acetonitrile decomposition. While the samples have many similar physical
      properties, X-ray photoelectron spectroscopy and transmission electron microscopy
      showed evidence that differences in the nanostructure and surface functional
      groups of the samples are likely to account for observed differences in oxygen
      reduction activity. The most active catalysts were prepared over alumina
      impregnated with up to 2 wt % Fe, although the catalysts that were prepared by
      acetonitrile pyrolysis over alumina with no metal doping still had significant
      activity. In comparison to a 20 wt % platinum on Vulcan carbon catalyst, the most
      active samples only have an additional 100 mV overpotential. The selectivity of
      the catalysts for complete oxygen reduction to water followed a trend similar to
      activity. The best selectivity to water versus peroxide obtained was 99%, or
      equivalently, an n of 3.98 (i.e., 3.98 electrons transferred out of a maximum of
      4 electrons per mole of oxygen that is reduced), as determined by rotating ring
      disk electrode testing.

PMID- 16970462
TI  - Sonochemical degradation of alkylbenzene sulfonate surfactants in aqueous
      mixtures.
AB  - The degradation of nonvolatile surfactants sodium 4-octylbenzene sulfonate (OBS)
      and dodecylbenzenesulfonate (DBS) and a nonvolatile nonsurfactant 4-ethylbenzene
      sulfonic acid (EBS), as single components and binary mixtures, were studied under
      354 kHz ultrasound. In addition, the effects of pulsed ultrasound on degradation
      were also examined. Results show that in mixtures of the surfactant OBS and
      nonsurfactant EBS, the surfactant is selectively degraded. The reduced
      degradation of EBS was dependent on the mixed molar ratio of EBS/OBS. The
      degradation of OBS was unaffected by the presence of EBS at a molar ratio of
      OBS/EBS > or = 1. Furthermore, OBS degradation was significantly enhanced under
      pulsed ultrasound. In OBS and DBS surfactant mixtures sonicated under pulsed
      ultrasound, surfactants strongly affected each other's degradation rates due to
      competition for the reaction sites on the cavitation bubble surfaces. OBS
      exhibits a faster degradation rate than DBS at shorter pulse intervals due to its
      faster rate of transfer to the cavitation bubble interfaces. At longer pulse
      intervals, DBS, which is more surface active, degrades faster than OBS due to the
      increased amounts of DBS accumulation on the bubble surfaces.

PMID- 16970463
TI  - Mechanistic aspects of HC-SCR over HZSM-5: hydrocarbon activation and role of
      carbon-nitrogen intermediates.
AB  - This study focuses on the mechanism of lean NO(2) reduction by hydrocarbons
      (propane, propene, and isobutane) over HZSM-5. In-situ FTIR measurements indicate
      a close correlation between formation of isocyanate species, consumption of water
      (formed in the reaction), and formation of amine species. The results in this
      investigation confirm our previously suggested reaction mechanism, which involves
      reaction of NO(+) species and hydrocarbon-derived species over Bronsted acid
      sites, forming isocyanate species. These species are hydrolyzed by water, forming
      amine species and, finally, N(2). Experiments with (18)O(2) show an enhanced
      oxidation of propane by oxygen, in the presence of NO(2). This effect can
      possibly be explained by a type of reaction mechanism where gas-phase and/or
      loosely bound NO(2) react with the adsorbed hydrocarbon-derived species (i.e.,
      carbenium ion adsorbates and/or alkenes), which then more easily react with
      oxygen.

PMID- 16970464
TI  - Multi-scale approach continuously relating the microstructure and the macroscopic
      mechanical properties of plaster pastes during their settings.
AB  - A new multi-scale experimental approach is proposed to continuously relate the
      microstructure and the macroscopic mechanical properties of plaster pastes during
      their settings. (1)H NMR relaxometry is used to follow continuously and not
      destructively, the degree of hydration and the microstructure evolution during
      the setting and hardening of plaster paste. Transmission of shear and
      compressional ultrasonic velocities enable the determination of macroscopic
      mechanical properties of the material during the setting. On the basis of similar
      behaviors of Young's modulus and NMR-population of confined water as function of
      the degree of hydration, we conclude that NMR gives a better understanding of the
      evolution of the microstructure at the origin of a better control of the
      macroscopic mechanical properties.

PMID- 16970465
TI  - Electrogenerated chemiluminescence of luminol on a gold-nanorod-modified gold
      electrode.
AB  - Electrogenerated chemiluminescence (ECL) of luminol on a gold-nanorod-modified
      gold electrode was studied, and five ECL peaks were obtained under conventional
      cyclic voltammetry in both neutral and alkaline solutions. Among them, four ECL
      peaks (ECL-1-4) were also observed on a gold-nanosphere-modified gold electrode,
      but the intensities of these ECL peaks were enhanced about 2-10-fold on a gold
      nanorod-modified gold electrode in neutral solution. One new strong ECL peak (ECL
      5) was obtained at -0.28 V (vs SCE) on a gold-nanorod-modified gold electrode in
      both neutral and alkaline solutions and enhanced with an increase in pH. In
      strong alkaline solutions, ECL-1 and ECL-2 on a gold-nanosphere-modified
      electrode were much stronger than those on a gold-nanorod-modified gold
      electrode, while ECL-3-5 appeared to only happen on a gold-nanorod-modified gold
      electrode. The emitter of all the ECL peaks was identified as 3-aminophthalate.
      The ECL peaks were found to depend on the scan direction, the electrolytes, the
      pH, and the presence of O(2) and N(2). The reaction pathways for ECL-4 have been
      further elucidated, and the mechanism of the new ECL peak (ECL-5) has been
      proposed. The results indicate that a gold-nanorod-modified gold electrode has a
      catalytic effect on luminol ECL different from that of a gold-nanosphere-modified
      gold electrode, revealing that the shape of the metal nanoparticles has an
      important effect on the luminol ECL behavior. The strong ECL of luminol in
      neutral solution obtained on a gold-nanorod-modified electrode may be used for
      the sensitive detection of biologically important compounds in physiological
      conditions.

PMID- 16970466
TI  - Can linear micelles bridge between two surfaces?
AB  - Surfactants are extensively used as stabilizers of colloidal particles, even
      though the use of high surfactant concentrations can induce a loss of the
      stability of the dispersion. The depletion mechanism is believed to be
      responsible for this instability. In this paper, we show that there exists an
      alternative interpretation, namely that wormlike micelles can bridge between two
      surfaces. Such a stalk-like object connecting two adsorbed bilayers is (in first
      order) stable when the endcap (free) energy of the wormlike micelle (in solution)
      is higher than the connection (free) energy of the stalk with the surface layer.
      As an example, we consider an aqueous solution of nonionic C(12)E(6) surfactants
      and use a molecularly realistic self-consistent field approach to evaluate the
      free-energy of bridge formation. It appears impossible to connect linear micelles
      to hydrophobic surfaces onto which a monolayer of surfactants exists, and stalks
      only occur with an exponentially low probability for very hydrophilic surfaces.
      However, at a wide regime of moderately hydrophilic surfaces the stalks are
      thermodynamically stable. In this regime, the adsorbed bilayers are typically
      only marginally stable. We identify a range of parameters for which such adsorbed
      bilayer ruptures around the stalk and then the wormlike micelle essentially
      connects (head-on) to the bare surface. The strength of interaction is of the
      order of the endcap energy which easily exceeds 10 k(B)T. The range of
      interactions is expected to be large as it is set by the characteristic size of
      the linear micelles in solution. The regime of moderately hydrophilic surfaces is
      relevant experimentally, and we conclude that surfactant-induced flocculation may
      well be the result of stalks. The depletion mechanism is only expected for
      systems with extremely hydrophobic and with very hydrophilic particles.

PMID- 16970467
TI  - Preparation and hydrogen storage properties of zeolite-templated carbon materials
      nanocast via chemical vapor deposition: effect of the zeolite template and
      nitrogen doping.
AB  - Carbon materials have been prepared using zeolite 13X or zeolite Y as template
      and acetonitrile or ethylene as carbon source via chemical vapor deposition (CVD)
      at 550-1000 degrees C. Materials obtained from acetonitrile at 750-850 degrees C
      (zeolite 13X) or 750-900 degrees C (zeolite Y) have high surface area (1170-1920
      m(2)/g), high pore volume (0.75-1.4 cm(3) g(-1)), and exhibit some structural
      ordering replicated from the zeolite templates. Templating with zeolite Y
      generally results in materials with higher surface area. High CVD temperature (>
      or =900 degrees C) results in low surface area materials that have significant
      proportions of graphitic carbon and no zeolite-type structural ordering. The
      nitrogen content of the samples derived from acetonitrile varies between 5 and 8
      wt %. When ethylene is used as a carbon precursor, high surface area (800-1300
      m(2)/g) materials are only obtained at lower CVD temperature (550-750 degrees C).
      The ethylene-derived carbons retain some zeolite-type pore channel ordering but
      also exhibit significant levels of graphitization even at low CVD temperature. In
      general, the carbon materials retain the particle morphology of the zeolite
      templates, with solid-core particles obtained at 750-850 degrees C while hollow
      shells are generated at higher CVD temperature (> or =900 degrees C). We observed
      hydrogen uptake of up to 4.5 wt % and 45 g H(2)/L (volumetric density) at -196
      degrees C and 20 bar for the carbon materials. The hydrogen uptake was found to
      be dependent on surface area and was therefore influenced by the choice of
      zeolite template and carbon source. Zeolite Y-templated N-doped carbons had the
      highest hydrogen uptake capacity. Gravimetric and volumetric methods gave similar
      uptake capacity at 1 bar (i.e., 1.6 and 2.0 wt % for zeolite 13X and Y-templated
      N-doped carbons, respectively). Our findings show that zeolite-templated carbons
      are attractive for hydrogen storage and highlight the potential benefits of
      functionalization (nitrogen-doping).

PMID- 16970468
TI  - A comparative study on electrochemical micromachining of n-GaAs and p-Si by using
      confined etchant layer technique.
AB  - The confined etchant layer technique has been applied to achieve effective three
      dimensional (3D) micromachining on n-GaAs and p-Si. This technique operates via
      an indirect electrochemical process and is a maskless, low-cost technique for
      microfabrication of arbitrary 3D structures in a single step. Br(2) was
      electrogenerated at the mold surface and used as an efficient etchant for n-GaAs
      and p-Si; l-cystine was used as a scavenger, for both substrates. The resolution
      of the fabricated microstructure depended strongly on the composition of the
      electrolyte, and especially on the concentration ratio of l-cystine to Br(-). A
      well-defined, polished Pt microcylindrical electrode was employed to examine the
      deviation of the size of the etched spots from the real diameter of the
      microelectrode. The thickness of the confined etchant layer can be estimated, and
      thus the composition of the electrolyte can be optimized for better etching
      precision. The etched patterns were approximately negative copies of the mold,
      and the precision of duplication could reach the micrometer level for p-Si and
      the submicrometer level for n-GaAs. Although the same etchant (Br(2)) and
      scavenger (l-cystine) were used in the etching solutions for GaAs and Si, the
      etching process, or mechanism, is completely different in the two cases. Compared
      with the fast etching process on GaAs in an etching solution with a concentration
      ratio of 3:1 of l-cystine to Br(-), the concentration ratio needs to be 50:1 for
      etching of Si. For the micromachining of Si, the addition of a cationic
      surfactant (cetyltrimethylammonium chloride, CTACl) is necessary to reduce the
      surface tension of the substrate and hence reduce the influence of evolution of
      the byproduct H(2). The function of the surfactant CTACl in comparison with an
      anionic surfactant (sodium dodecyl sulfate) was studied in contact-angle
      experiments and micromachining experiments and then is discussed in detail.

PMID- 16970469
TI  - Theoretical study of Cu(I)Y zeolite: structure and electronic properties.
AB  - The structural and electronic properties of the accessible Cu(I) site of a
      faujasite-type zeolite have been studied, by use of large cluster models and a
      density functional theory-based methodology. We demonstrate that the local ideal
      C(3) symmetry of the Cu(I) site II is broken. The Cu(I) cation is bonded to the
      zeolite framework by one bond of about 2.26 A and two shorter ones of 2.07 A. We
      demonstrate that only one cation position exists at this site. This result is
      also confirmed by a molecular electrostatic potential analysis. We show that
      local properties at site II, as well as the global properties of the solid
      (frontier orbitals), do not depend on the Al and cation distribution and only
      slightly on the cocation nature. Taking into account the present results and well
      known experimental data, we propose that specific catalytic behaviors are
      correlated with local response properties, such as the local acid strength or, in
      other reactions, specific local architecture or confinement.

PMID- 16970470
TI  - Cation migration upon adsorption of methanol in NaY and NaX faujasite systems: a
      molecular dynamics approach.
AB  - Molecular dynamics simulations have been carried out to address the question of
      cation migration upon adsorption of methanol in NaY and NaX faujasite systems as
      a function of the loading. For NaY, it has been shown that, at low and
      intermediate loadings, SII cations can migrate toward the center of the supercage
      due to strong interactions with the adsorbates, followed by a hopping of SI' from
      the sodalite cage into the supercage to fill the vacant SII site. A SI' cation
      can also migrate across the double six ring and takes a SI' vacant position. SI
      cations mainly remain trapped in their initial sites whatever the loading. At
      high loading, only limited motions are observed for SII cations due to steric
      effects induced by the presence of adsorbates within the supercage. For NaX, the
      SIII' cations which occupy the most accessible adsorption sites are significantly
      moving upon coordination to the methanol molecules; the extent of this mobility
      exhibits a maximum for 48 methanol molecules per unit cell before decreasing at
      higher loadings due to steric hindrance. In addition, the SI' and SII cations
      remain almost trapped in their initial sites whatever the loading. Indeed, the
      most probable migration mechanism involves SIII' cation displacements into nearby
      SIII' sites.

PMID- 16970471
TI  - Two dissociation pathways of water and ammonia on the Si(001) surface.
AB  - Using first-principles density-functional calculations, we investigated two
      competing pathways for the dissociation of water and ammonia on a Si(001)
      surface. For both systems, we found that, in addition to the conventionally
      accepted intradimer transfer of the H atom, the interdimer transfer of the H atom
      can be equally probable with the same reaction mechanism. Our analysis shows that
      the two dissociation pathways occur through the Lewis acid-base reaction between
      the partially positive H ion and the electron-abundant up atom of the buckled Si
      dimer. The result of the interdimer H transfer not only supports a recently
      proposed model for C-defect on Si(001) but also corresponds to the recent
      scanning tunneling microscopy data of ammonia dissociation on Si(001).

PMID- 16970472
TI  - Ab initio and work function and surface energy anisotropy of LaB6.
AB  - Lanthanum hexaboride is one of the cathode materials most used in high-power
      electronics technology, but the many experimental results do not provide a
      consistent picture of the surface properties. Therefore, we report the first ab
      initio calculations of the work functions and surface energies of the (001),
      (011), (111), (112), and (012) surfaces by considering the different surface
      terminations and structural relaxation. Either the (111)B- or the (001)La
      terminated surface is the most stable, depending on La chemical potential. The
      work function of the latter is the lowest (2.07 eV) of the surfaces considered.
      Both the work function and surface energy decrease further when surface La is
      replaced by Ba and become, respectively, 1.43 and 7.7 eV/nm(2) at the chemical
      potentials of elemental lanthanum and barium bulk. These results compare
      favorably with previous work on the intermetallics BaAl(4), CaAl(4), and
      BaAuIn(3). Their most stable surfaces possess the lowest work function. Now, we
      study a compound with a decidedly different crystal type and with its
      constituting elements from column 3 of the periodic table, of which one is
      nonmetallic.

PMID- 16970473
TI  - Oscillating bubble SHG on surface elastic and surface viscoelastic systems: new
      insights in the dynamics of adsorption layers.
AB  - Surface rheology governs a great variety of interfacial phenomena such as foams
      or emulsions and plays a dominant role in several technological processes such as
      high-speed coating. Its major difference with bulk rheology resides in the high
      compressibility of the surface phase, which is the direct consequence of the
      molecular exchange between adsorbed and dissolved species. In analogy to bulk
      rheology, a complex surface dilational modulus, epsilon, which captures surface
      tension changes upon defined area changes of the surface layer, can be defined.
      The module epsilon is complex, and the molecular interpretation of the
      dissipative process that gives rise to the imaginary part of the module is
      subject to some controversy. In this contribution, we used the oscillating bubble
      technique to study the surface dilational modulus in the mid-frequency range. The
      dynamic state of the surface layer was monitored by a pressure sensor and by
      surface second-harmonic generation (SHG). The pressure sensor measures the real
      and imaginary part of the modulus while SHG monitors independently the surface
      composition under dynamic conditions. The experiment allows the assessment of the
      contribution of the compositional term to the surface dilational modulus epsilon.
      Two aqueous surfactant solutions have been characterized: a surface elastic and a
      surface viscoelastic solution. The elastic surface layer can be described within
      the framework of the extended Lucassen-van den Tempel Hansen model. The change in
      surface concentration is in phase with the relative area change of the surface
      layer, which is in strong contrast with the results obtained from the surface
      viscoelastic solution. Here, surface tension, area change, and surface
      composition are phase-shifted, providing evidence for a nonequilibrium state
      within the surface phase. The data are used to assess existing surface rheology
      models.

PMID- 16970474
TI  - Active sites in working bifunctional GaH-TON aromatization catalysts: kinetic
      evaluation.
AB  - The conversion of light alkanes to high value aromatics proceeds with a high
      selectivity over bifunctional, gallium (Ga) containing zeolite catalysts. It is
      generally agreed that Ga sites are involved in dehydrogenation reaction steps and
      that the zeolite acid sites catalyze cracking, oligomerization, and cyclization
      reactions. However, understanding of the precise roles of the acid and Ga sites
      in the reaction mechanisms is significantly hampered since the number of these
      sites in working catalysts is not known. This paper describes a kinetic approach
      to evaluation of the acid and Ga active sites in working Ga containing TON
      zeolite catalysts that relies on the analysis of the rates of formation of the
      primary products of a n-butane aromatization reaction. Our results show that the
      rate of ethane formation at low n-butane conversions can be used as a
      quantitative estimate of acidity in working bifunctional zeolite catalysts and
      demonstrate, for the first time, a significant decrease in the number of Bronsted
      acid sites in the Ga containing catalysts under reaction conditions: around 47
      and 79% for the catalysts with Ga loading of 1.5 and 2.5 wt %, respectively. We
      conclude that the reduction in acidity is associated with the formation of
      catalytically active Ga(+) ions and obtain estimates for the number and steady
      state turnover activity of the acid and Ga active sites in n-butane
      transformation. We anticipate that our work will facilitate understanding of the
      precise roles of the acid and Ga sites in the mechanisms of alkane aromatization
      and, as a far-reaching implication, will prompt wider use of detailed kinetic
      studies for the evaluation of active sites in working catalysts.

PMID- 16970475
TI  - Sum frequency generation spectroscopy and double-layer capacitance studies of the
      1-butyl-3-methylimidazolium dicyanamide-platinum interface.
AB  - The orientation of the cation and the anion of 1-butyl-3-methylimidazolium
      dicyanamide at the platinum-liquid interface, using sum frequency generation
      (SFG) spectroscopy is reported. Sum frequency spectra at two different
      polarizations and different potentials are recorded, and analysis of polarization
      dependent spectra is performed to estimate the orientation of the dicyanamide
      anion and the alkyl and ring moieties in the cation as a function of the
      potential applied to the platinum electrode. In addition, cyclic voltammetry and
      electrochemical impedance spectroscopy are conducted. A model of the double-layer
      structure at the electrified interface is presented from the analysis of
      capacitance and SFG data.

PMID- 16970476
TI  - TiO2 surface active sites for water splitting.
AB  - The mechanism of photoreactivity between the TiO(2) surface and H(2)O, and the
      related charge transfer, is considered in terms of both collective and local
      properties. It is shown that the effective charge transfer between TiO(2) and
      water requires the presence of surface active sites that are able to provide
      electron holes to adsorbed water molecules. Titanium vacancies located at or near
      the surface are identified as the active sites for water adsorption leading to
      the formation of an active complex and resulting, in consequence, in water
      splitting. A model of the photoreactivity between the TiO(2) surface and water is
      proposed. This model indicates that the photoreactivity of the TiO(2)-based
      photoelectrode may be enhanced through imposition of the surface active sites (Ti
      vacancies) in a controlled manner by surface engineering.

PMID- 16970477
TI  - Hydration of hydrophobic solutes treated by the fundamental measure approach.
AB  - We have developed a method to calculate the hydration of hydrophobic solutes by
      the fundamental measure theory. This method allows us to carry out calculations
      of the density profile and the hydration energy for hydrophobic molecules. An
      additional benefit of the method is the possibility to calculate interaction
      forces between solvated nanoparticles. Based on the designed method, we calculate
      hydration of spherical solutes of various sizes from one angstrom up to several
      nanometers. We have applied methods to evaluate the free energies, the
      enthalpies, and the entropies of hydrated rare gases and hydrocarbons. The
      obtained results are in agreement with available experimental data and
      simulations.

PMID- 16970478
TI  - Structure of an accurate ab initio model of the aqueous Cl- ion at high
      temperatures.
AB  - The structure of an accurate ab initio model of aqueous chloride ion was
      calculated at two high-temperature state points (573 K, 0.725 g/cm(3) and 723 K,
      0.0098 g/cm(3)) by a two-step procedure. First, the structure of an approximate
      model was calculated from a molecular dynamics simulation of the model. Then the
      difference between the structure of the ab initio model and the approximate model
      was calculated by non-Boltzmann weighting of a sample of configurations taken
      from the approximate model simulation. Radial distribution functions, average
      coordination numbers, the distribution of coordination numbers, an analysis of
      orientations of water in the first coordination shell, and the free energy of
      hydration of the chloride ion are reported for both state points. The most common
      water structure has one hydrogen close to the chloride ion and one pointing away
      (46% at 573 K and 57% at 723 K). Waters in the first coordination shell that are
      not strongly bound to the chloride ions are common. Several variations of the
      method were tested. Models in which the water-water interaction is calculated
      with ab initio methods predict only a slightly different structure than models in
      which water-water interactions are determined from the approximate models.
      Similarly, using the approximate model for solute-water interactions when the
      water is far from the chloride ion did not affect the results. Uncertainties due
      to the limited sample of configurations are estimated and found to be small. The
      results are in qualitative agreement with X-ray and neutron diffraction
      experiments and with simulations of approximate models.

PMID- 16970479
TI  - Theoretical studies of energy transfer rates of secondary explosives.
AB  - Understanding the mechanism of shock-induced chemical reaction in secondary
      explosives is necessary to pursue the development and the safe use of new
      explosives having high performance and low sensitivity. In an effort to
      understand the mechanism, the energy transfer rates of such secondary explosives
      as PETN(I), PETN(II), delta-HMX, alpha-HMX, beta-HMX, RDX, ANTA, DMN, and NM have
      been evaluated based on the formula derived by Fried and Ruggiero [Fried, L. E.;
      Ruggiero, A. J. J. Phys. Chem. 1994, 98, 9786]. The energy transfer rates were
      determined in terms of the density of vibrational states and the unharmonic
      vibron-phonon coupling term, which were calculated by using a flexible potential
      containing both intra- and intermolecular terms. For the secondary explosives, a
      good correlation was found between the energy transfer rates and the impact
      sensitivity. The energy transfer rates are several times faster for the
      explosives with higher sensitivity such as PETN, HMX, and RDX than those with
      lower sensitivity such as ANTA, DMN, and NM. The calculations presented suggest
      the energy transfer rate in secondary explosive crystals is a significant factor
      in their sensitivity and introduction of double bond, or hydrogen bonds, or caged
      structure into secondary explosives is expected to decrease the sensitivity.

PMID- 16970480
TI  - Heterogeneous association in methanol-carbon tetrachloride mixtures.
AB  - A lattice model developed for the calculation of the equilibrium distribution of
      molecular clusters in methanol-carbon tetrachloride mixtures is modified in order
      to account for an entropy component associated to the binding of CCl(4) with the
      nondonating end of methanol clusters. This entropy contribution is shown to
      affect significantly the H-bonding energy estimates based on the use of the model
      for the analysis of both the static dielectric response and the Raman O-H
      stretching spectra of these mixtures. The agreement with some results from
      numerical simulations turns out to be improved. In particular, the new value of
      approximately 6.2 kcal/mol found for the H-bonding energy (to be compared with
      approximately 3.2 kcal/mol yielded by the previous version of the model) is close
      to the results of simulation (approximately 5.5 kcal/mol). The H-bonding energy
      is also estimated by fitting the excess mixing enthalpy with an empirical
      polynomial expansion, complemented by an association contribution derived from
      the model. The agreement is good in this case, too.

PMID- 16970481
TI  - Interface film resistivities for heat and mass transfers-integral relations
      verified by non-equilibrium molecular dynamics.
AB  - Integral relations that predict interface film transfer coefficients for
      evaporation and condensation have recently been derived. According to these
      relations, all coefficients can be calculated for one-component systems, using
      the thermal resistivity and the enthalpy profile through the interface. The
      integral relations were tested in this work using nonequilibrium molecular
      dynamics simulations for argon-like particles and n-octane molecules. The
      simulations confirm the integral relations within the accuracy of the calculation
      for both systems. Evidence is presented for the existence of an excess thermal
      resistivity on the gas side of the surface, and the fact that this property is
      decisive for interface heat and mass transfer coefficients. The integral
      relations were used to predict the mass transfer coefficient for n- octane as a
      function of surface tension. The findings are important for modeling of one
      component phase transitions.

PMID- 16970482
TI  - Computer simulation of the linear and nonlinear optical susceptibilities of p
      nitroaniline in cyclohexane, 1,4-dioxane, and tetrahydrofuran in quadrupolar
      approximation. II. Local field effects and optical susceptibilitities.
AB  - This is the second part of a study to elucidate the local field effects on the
      nonlinear optical properties of p-nitroaniline (pNA) in three solvents of
      different multipolar character, that is, cyclohexane (CH), 1,4-dioxane (DI), and
      tetrahydrofuran (THF), employing a discrete description of the solutions. By the
      use of liquid structure information from molecular dynamics simulations and
      molecular properties computed by high-level ab initio methods, the local field
      and local field gradients on p-nitroaniline and the solvent molecules are
      computed in quadrupolar approximation. To validate the simulations and the
      induction model, static and dynamic (non)linear properties of the pure solvents
      are also computed. With the exception of the static dielectric constant of pure
      THF, a good agreement between computed and experimental refractive indices,
      dielectric constants, and third harmonic generation signals is obtained for the
      solvents. For the solutions, it is found that multipole moments up to two orders
      higher than quadrupole have a negligible influence on the local fields on pNA, if
      a simple distribution model is employed for the electric properties of pNA.
      Quadrupole effects are found to be nonnegligible in all three solvents but are
      especially pronounced in the 1,4-dioxane solvent, in which the local fields are
      similar to those in THF, although the dielectric constant of DI is 2.2 and that
      of the simulated THF is 5.4. The electric-field-induced second harmonic
      generation (EFISH) signal and the hyper-Rayleigh scattering signal of pNA in the
      solutions computed with the local field are in good to fair agreement with
      available experimental results. This confirms the effect of the "dioxane anomaly"
      also on nonlinear optical properties. Predictions based on an ellipsoidal Onsager
      model as applied by experimentalists are in very good agreement with the discrete
      model predictions. This is in contrast to a recent discrete reaction field
      calculation of pNA in 1,4-dioxane, which found that the predicted first
      hyperpolarizability of pNA deviated strongly from the predictions obtained using
      Onsager-Lorentz local field factors.

PMID- 16970483
TI  - Simulation of Ca2+ and Mg2+ solvation using polarizable atomic multipole
      potential.
AB  - The alkaline earth metals calcium and magnesium are critically involved in many
      biomolecular processes. To understand the hydration thermodynamics of these ions,
      we have performed molecular dynamics simulations using a polarizable potential.
      Particle-mesh Ewald for point multipoles has been applied to the calculation of
      electrostatic interactions. The parameters in this model have been determined
      from an ab initio quantum mechanical calculation of dimer interactions between
      ions and water. Two methods for ion solvation free energy calculation, free
      energy perturbation, and the Bennett acceptance ratio have been compared. Both
      predict results consistent with other theoretical estimations while the Bennett
      approach leads to a much smaller statistical error. Based on the Born theory and
      the ion-oxygen radial distribution functions, we estimate the effective size of
      the ions in solution, concluding that K(+) > Na(+) congruent with Ca(2+) >
      Mg(2+). There appears to be much stronger perturbation in water structure,
      dynamics, and dipole moment around the divalent cations than the monovalent K(+)
      and Na(+). The average water coordination numbers for Ca(2+) and Mg(2+) are 7.3
      and 6, respectively. The lifetime of water molecules in the first solvation shell
      of Mg(2+) is on the order of hundreds of picoseconds, in contrast to only few
      picoseconds for Ca(2+), K(+), or Na(+).

PMID- 16970484
TI  - Analysis of the effect of translation-rotation coupling on diffusion along the
      molecular axes.
AB  - The analysis of the microscopic diffusion processes of CO(2) and H(2)O in the
      coordinate system defined by the molecular orientation allows a new criterion to
      be introduced which provides information on the short and long time behavior of
      the rotation-translation coupling as well as to quantify the strength of this
      coupling. We discuss the general conditions under which this affects the
      translation diffusion "seen" by the molecule along its molecular axes. The
      results show that the translation-rotation coupling is correlated to the local
      environment in shaping the longitudinal and transversal translation dynamics of a
      molecule at a microscopic level.

PMID- 16970485
TI  - Interactions of nitrous oxide with fluorinated liquids.
AB  - The interactions of nitrous oxide with fluorinated liquids are investigated by
      reporting original experimental results on gas solubility and interpreting them
      using molecular simulation. Nitrous oxide is highly soluble in the three
      fluorinated liquids studied-perfluorooctane, 1-bromoperfluorooctane
      (perfluorooctylbromide), and perfluorohexylethane-with mole fraction solubilities
      on the order of 0.03 under ambient conditions. An intermolecular potential model
      was developed for nitrous oxide, with a functional form of the Lennard-Jones plus
      point charges type, adjusted to the experimental multipole moments and to vapor
      liquid equilibrium properties. The solubility of nitrous oxide in perfluorocarbon
      liquids was calculated by molecular simulation methods, and a dissimilar
      interaction parameter of 0.92 in the Lennard-Jones well-depths between solute and
      solvent had to be introduced to reach agreement with the experimental results,
      similar to what is found for hydrocarbon-fluorocarbon interactions. The structure
      of the solutions was studied by analysis of solute-solvent radial distribution
      functions, showing that, although electrostatic interactions are not predominant,
      a small orientational effect is still present between the dipole of nitrous oxide
      and those of the substituted fluorinated liquids.

PMID- 16970486
TI  - Glass transition phenomena in two-component plastic crystals: study of
      hexasubstituted benzenes.
AB  - We have critically examined the relaxation that is known to occur in the
      crystalline phase of pentachloronitrobenzene (PCNB) and 2,3,4,5,6
      pentabromotoluene using dielectric spectroscopy and differential scanning
      calorimetry (DSC). Within the resolution of our experimental setup, a relaxation
      process similar to that of the primary (or alpha-) relaxation is found. A slight
      deviation from Arrhenius behavior is noticed only in the vicinity of the glass
      transition temperature (T(g)). This deviation and a small steplike change found
      in the DSC scans at T(g) indicates that the "fragility" of these plastic crystals
      is rather low. However, in PCNB, the dielectric strength (Deltaepsilon) of the
      above said alpha-process did not change appreciably with temperature, and,
      interestingly, a small addition of an impurity such as pentachlorobenzene (PCB)
      to the molten state of PCNB drastically lowered the dielectric strength and the
      calorimetric signature of glass transition phenomena in the DSC data at T(g). The
      room-temperature powder X-ray diffraction measurements in combination with the
      DSC data in the melting temperature region did not indicate any observable change
      in the crystalline structure. A residual alpha-process with no significant change
      in the shape of the dielectric spectrum indicates that the hindrance to the
      rotational motion of PCNB molecules is caused by the presence of a small number
      of PCB molecules in the crystalline lattice of PCNB over a certain region.
      Outside of this region, the original PCNB disordered phase is preserved, which is
      the origin of the residual alpha-process. With a further increase in PCB
      concentration, the alpha-process, characteristic of pure PCNB, vanishes, and
      instead another relaxation develops. This process is explained with the help of a
      solid-liquid phase diagram of the alpha-process of the plastic phase of 2:1 and
      1:2 compound formations, which are stable below 386 +/- 1 and 366 +/- 1 K,
      respectively.

PMID- 16970487
TI  - Thermodynamic studies of molecular interactions in aqueous alpha-cyclodextrin
      solutions: application of McMillan-Mayer and Kirkwood-Buff theories.
AB  - Osmotic vapor pressure and density measurements were made for aqueous alpha
      cyclodextrin (alpha-CD) solutions in the temperature range between 293.15 and
      313.15 K. The experimental osmotic coefficient data were used to determine the
      corresponding activity coefficients and the excess Gibbs free energy of
      solutions. Further, the activity data obtained at different temperatures along
      with the enthalpies of dissolution (reported in the literature) were processed to
      obtain the excess enthalpy and excess entropy values for the solution process.
      The partial molar entropies of water and of alpha-cyclodextrin were calculated at
      different temperatures and also at different concentrations of alpha-CD. Using
      the partial molar volume data at infinite dilution, the solute-solvent cluster
      integrals were evaluated which yielded information about solute-solvent
      interactions. The application of McMillan-Mayer theory of solutions was made to
      obtain osmotic second and third virial coefficients which were decomposed into
      attractive and repulsive contributions to solute-solute interactions. The second
      and third osmotic virial coefficients are positive and show minimum at 303.15 K.
      The Kirkwood-Buff (KB) integrals G(ij), defined by the equation G(ij) =
      f(infinity)0 (g(ij)- 1)4pir(2) dr, have been evaluated using the experimental
      osmotic coefficient (and hence activity coefficient) and partial molar volume
      data. The limiting values of KB integrals, G(ij)(0) are compared with molecular
      interaction parameters (solute-solute i.e., osmotic second virial coefficient)
      obtained using McMillan-Mayer theory of solutions. We found an excellent
      agreement between the two approaches.

PMID- 16970488
TI  - Characterization of the solvation and transport of the hydrated proton in the
      perfluorosulfonic acid membrane nafion.
AB  - The solvation and transport properties of the sulfonate-hydronium ion pair have
      been studied in hydrated Nafion through molecular dynamics simulation. Explicit
      proton and charge delocalization of the excess proton transport, via the
      Grotthuss hopping mechanism, were treated using the self-consistent multistate
      empirical valence bond (SCI-MS-EVB) method. The nature of the sulfonate-hydronium
      ion pair was characterized through analysis of free-energy profiles. It was found
      that, in general, the excess proton is solvated between two water molecules of a
      Zundel moiety while in the contact ion pair position, but then it transitions to
      an Eigen-like configuration in the solvent-separated pair position. Furthermore,
      the positive charge associated with the excess proton passes between the contact
      and solvent-separated ion pair positions through the Grotthuss mechanism rather
      than simple vehicular diffusion. The total proton diffusion was decomposed into
      vehicular and Grotthuss components and were found to be of the same relative
      magnitude, but with a strong negative correlation resulting in a smaller overall
      diffusion. Correlated motions between the ion pair were examined through the
      distinct portion of the van Hove correlation function, and a characteristic time
      scale of approximately 425 ps was observed. Additionally, the association of the
      hydrated proton with the hydrophobic polymer backbone suggests its amphiphile
      like behavior (see Acc. Chem. Res. 2006, 39, 143; Phys. Rev. 1954, 95, 249; J.
      Chem. Phys. 2005, 123, 084309).

PMID- 16970489
TI  - Tail aggregation and domain diffusion in ionic liquids.
AB  - An extended multiscale coarse-graining model for ionic liquids is used to
      investigate the liquid crystal-like phase in certain ionic liquids. The tail
      groups of the cations with a sufficient side-chain length are found to aggregate,
      forming spatially heterogeneous domains, due to the competition between the
      electrostatic interactions between the charged head groups and the anions and the
      collective short-range interactions between the neutral tail groups. With a
      sufficiently long alkyl chain at a low enough temperature, the tail domains
      remain relatively stable, despite the diffusion of individual ions in the liquid
      phase. With increasing temperature, the average tail domains begin to diffuse,
      while beyond a transition temperature, their average density has an almost
      uniform distribution, although the tail groups still form instantaneous domains.

PMID- 16970490
TI  - Structure, metastability, and electron density of Al lattices in light of the
      model of anions in metallic matrices.
AB  - This paper reports a theoretical investigation of the structure, stability, and
      electron charge density of cubic, rhombohedral, hexagonal, and monoclinic Al
      lattices. The equations of state and the elastic constants are computed from
      total energy calculations at different volumes and unit cell strains using the
      density functional theory approximation. The topology of the electron density is
      analyzed within the crystalline implementation of the atoms in molecules
      formalism. The results are discussed in light of the so-called anions in metallic
      matrices model, which permits the interpretation of the chemical bonding and the
      explanation of the existence of particular symmetries of inorganic crystals.
      First, the Al sublattices are identified as the reference building blocks of
      AlX(3) (X = F, Cl, OH) compounds. The calculations reveal that the equilibrium
      zero-pressure Al-Al shortest distance is around 2.75 A in all of the Al matrixes,
      similar to the value observed in the stable face centered cubic structure of Al
      at room conditions. Second, at their zero-pressure equilibrium geometries, the Al
      sublattices are found to fulfill the mechanical stability criteria or,
      alternatively, to show mechanical instabilities that are compatible with the
      distortions observed for the structures in AlX(3) crystals. However, at the
      equilibrium volumes of the AlX(3) crystals, all of the Al matrices violate the
      spinodal condition, and the cohesion and stabilization are provided by the
      nonmetallic X atoms. Third, the structural anisotropy of the Al sublattices seems
      to be the main factor to discriminate metallic matrices able to host nonmetallic
      elements. The inhomogeneities of the electron charge density, which favor the
      arrival of nonmetallic elements and the crystal formation, are notably enhanced
      in passing from the fcc structure of pure Al to the less isotropic Al matrices
      observed in AlX(3) compounds.

PMID- 16970491
TI  - Probing the nucleation mechanism for the binary n-nonane/1-alcohol series with
      atomistic simulations.
AB  - The AVUS-HR approach, which combines histogram reweighting with aggregation
      volume-bias Monte Carlo nucleation simulations using self-adaptive umbrella
      sampling, was extended to multicomponent nucleation systems. It was applied to
      investigate the homogeneous vapor-liquid nucleation for the binary n-nonane/1
      alcohol series, including the n-nonane/methanol, n-nonane/ethanol, n-nonane/1
      propanol, n-nonane/1-butanol, n-nonane/1-hexanol, and n-nonane/1-decanol systems.
      The simple transferable potentials for phase equilibria-united atom force field
      was used in this investigation. It was found that the nucleation free energy
      (NFE) contour plots obtained for these binary n-nonane/1-alcohol nucleation
      systems exhibit rather interesting mechanistic features, some of which are
      distinct from other binary systems previously studied (such as water/ethanol and
      water/n-nonane). In addition, the NFE profiles show a subtle evolution with the
      increase in alcohol chain length, from a somewhat two-pathway type of shape as
      observed for the n-nonane/methanol system to a more normal single-pathway one for
      systems involving longer alcohols (1-hexanol and 1-decanol). In contrast, the NFE
      maps obtained for the other three binary systems involving those medium-length
      alcohols display the most striking feature with the saddle point stretched almost
      all the way from the n-nonane-enriched to the alcohol-enriched domain, implying
      that multiple pathways coexist on the nucleation map. These free energy profiles
      were shown to be consistent with the non-ideal nucleation behavior observed
      experimentally for this binary series, namely, a rather reluctant conucleation of
      the alcohols with n-nonane. In particular, this non-ideal behavior becomes more
      severe with a decrease in the alcohol chain length. Also, analysis of the
      compositions of the critical nuclei indicates a reluctant mixing behavior between
      these two species, i.e., depletion of the alcohol at low alcohol activity or
      depletion of n-nonane at low n-nonane activity, in agreement with the
      experimental interpretations. Furthermore, a microscopic inhomogeneity is present
      inside these critical nuclei, that is, alcohols aggregate via hydrogen bonds
      forming alcohol-enriched domains.

PMID- 16970492
TI  - Monte Carlo study of supramolecular polymer fractionation: selective removal of
      chain stoppers by phase separation.
AB  - Supramolecular polymers consist of bifunctional monomers that join and break
      reversibly. Supramolecular polymer solutions are often polluted by monofunctional
      contaminants, which drastically reduce the chain-forming capabilities of the
      system. Unfortunately, the monofunctional contaminants are difficult to remove
      due to the physical and chemical resemblance with the bifunctional counterparts.
      In this paper, we present a method to specifically remove the monofunctional
      contaminants from a supramolecular polymer solution. The general idea is to
      induce phase separation by decreasing the solvent quality and to remove the most
      dilute phase. This concept is explored by means of a recently developed Monte
      Carlo scheme to calculate the compositions of the coexisting liquid phases. The
      simulations provide a proof of principle that the proposed purification method is
      suitable to remove the monofunctional contaminants efficiently. The calculations
      indicate that, at the right experimental conditions, the vast majority of the
      monofunctional contaminants can be removed in this way while retaining most of
      the bifunctional monomers. Because of the general nature of the arguments
      presented here, it is to be expected that the results are applicable to a large
      variety of supramolecular systems. Moreover, the method is very suitable for
      large-scale applications because only solvent is added and no tedious
      chromatographic steps are required.

PMID- 16970493
TI  - Ground-state structures and vertical excitations for the kindling fluorescent
      protein asFP595.
AB  - Geometry configurations of a large fraction of the kindling fluorescent protein
      asFP595 around the chromophore region were optimized by using the effective
      fragment potential quantum mechanical-molecular mechanical (QM/MM) method. The
      initial coordinates of heavy atoms were taken from the structure from the Protein
      Data Bank archive corresponding to the dark-adapted state of the Ala143 --> Gly
      mutant of asFP595. Optimization of geometry parameters was performed for all
      internal coordinates in the QM part composed of the chromophore unit and the side
      chains of His197, Glu215, and Arg92 as well as for positions of effective
      fragments constituting the MMpart. The structures corresponding to the anion
      trans, anion cis, and zwitterion trans moieties were considered among various
      alternatives for the chromophore unit inside the protein matrix. The QM/MM
      simulations show that the protein environment provides stabilization for the
      trans-zwitterion isomer compared to the gas-phase conditions. By using the
      multiconfigurational CASSCF and the time-dependent density functional theory
      calculations, we estimated positions of spectral bands corresponding to vertical
      S(0)-S(1) transitions. The results of simulations support the assumption that the
      dark state of asFP595 corresponds to the anionic or zwitterionic trans
      conformation, while the kindled state corresponds to the anionic cis
      conformation.

PMID- 16970494
TI  - Solvent-dependent photophysics of 1-cyclohexyluracil: ultrafast branching in the
      initial bright state leads nonradiatively to the electronic ground state and a
      long-lived 1npi* state.
AB  - The modified nucleic acid base, 1-cyclohexyluracil, was studied by femtosecond
      transient absorption spectroscopy in protic and aprotic solvents of varying
      polarity. UV excitation at 267 nm populates the lowest-energy bright state, a
      (1)pipi* state, which has a lifetime of 120-270 fs, depending on the solvent. In
      all solvents, this initial bright state population bifurcates with approximately
      60% undergoing subpicosecond nonradiative decay to the electronic ground state
      and the remaining population branching to a singlet dark state. The latter
      absorbs between 340 and 450 nm. The latter state is assigned to the lowest-energy
      (1)npi* state. It decays to the electronic ground state with a lifetime that
      varies from 26 ps in water to at least several nanoseconds in aprotic solvents.
      The results suggest that the two nonradiative decay pathways identified for
      photoexcited uracil in recent quantum chemical calculations (Matsika, S. J. Phys.
      Chem. A. 2004, 108, 7584) are simultaneously operative in a wide variety of
      solvent environments. The lowest-energy triplet state was also detected by
      transient absorption. The triplet population appears in a few picoseconds and is
      not formed from the thermalized (1)npi* state. It is suggested that high spin
      orbit coupling is found only along initial segments of the nonradiative decay
      pathways. Efficient intersystem crossing prior to vibrational cooling offers a
      possible explanation for the wavelength-dependent triplet yields seen in single
      DNA bases.

PMID- 16970495
TI  - Optical properties of N-succinimidyl bithiophene and the effects of the binding
      to biomolecules: comparison between coupled-cluster and time-dependent density
      functional theory calculations and experiments.
AB  - We report a joint theoretical-experimental study on the optical properties of 5-N
      succinimidyl-2,2'-bithiophene (NS-2T), a prototype system for a new class of
      biomarkers. Time-dependent density functional theory (TD-DFT) and approximate
      coupled-cluster single and doubles (CC2) calculations are performed in the ground
      and excited states. Theoretical results are compared with absorption,
      photoluminescence (PL), time-resolved PL, and PL quantum efficiency measurements.
      The excited state of NS-2T has a larger dipole moment as compared to that of the
      ground state, explaining the experimental shift of the PL peak in solvents of
      different polarity, and a smaller intersystem crossing (ISC) rate as compared to
      that of isolated bithiophene (2T), explaining the increased PL quantum
      efficiency. We also studied two model systems to describe the effects of the
      covalent binding of NS-2T to biomolecules and proteins with the epsilon-NH(2)
      lysine groups. These model systems show optical properties closer to 2T, as the
      PL quantum efficiency is reduced due to the increased ISC rate. Theoretical
      calculations and experimental results show that covalent binding of NS-2T to a
      biomolecule will blue-shift the absorption but not the photoluminescence. CC2 and
      TD-DFT can very well describe the absorption and photoluminescence energies of
      all three systems, but the presence of several charge-transfer transitions in the
      TD-DFT spectrum of NS-2T required the use of a correlated method to validate the
      TD-DFT results.

PMID- 16970496
TI  - Structures of nucleobases trapped within Au triangles and its effects on hydrogen
      bonding in base pairs of DNA.
AB  - Nucleobases (adenine (A), thymine (T), cytosine (C), and guanine (G)) trapped
      within two metal clusters such as Au(3) undergo expansion. Our investigation
      reveals that this primarily arises due to the concomitant increase in all the
      bond lengths in molecules. Such expansion of the molecules can be qualitatively
      understood on the basis of classical harmonic potentials in the bonds and loss of
      aromaticity in the rings. Specifically, the highly electronegative O and N
      elements in the base pairs anchor to Au atoms and form X-Au bonds, which leads to
      charge redistribution within the molecules. As a very important consequence of
      this, the nature of the hydrogen bonds (in Au(3)-A...T-Au(3) and in Au(3)-G...C
      Au(3)) change substantially within these electrodes in comparison to gas-phase
      structures. These hydrogen bonds have a single-well potential energy profile (of
      the type N...H...O and N...H...N) instead of double-well potentials (like N-H...O
      or N-H...N/ N...H-N types). A detailed energy calculation along the proton
      movement pathway supports our conclusions.

PMID- 16970497
TI  - A time-dependent density functional theory investigation of the spectroscopic
      properties of the beta-subunit in C-phycocyanin.
AB  - By using time-dependent density functional theory combined with the polarizable
      continuum model, a satisfactory assignment of the absorption and circular
      dichroism spectra and energy transfer flow of the beta-subunit in C-phycocyanin
      (C-PC) was achieved when the protonation of beta-84 and beta-155 phycocyanobilin
      (PCB) and their interaction with the protein moiety in C-PC have been taken into
      account. We attribute the main peak for both beta-84 and beta-155 as arising from
      the pi electron excitation of the pyrrole rings and the shoulder peak as arising
      from the charge transfer from the asparate residue to PCBH(+). The satisfactory
      agreement between theory and experiment suggests that Forster resonance theory
      prevails such that energy transfer occurs from beta(s) (beta-155) to beta(f)
      (beta-84).

PMID- 16970498
TI  - Contributions of NH...O and CH...O hydrogen bonds to the stability of beta-sheets
      in proteins.
AB  - Ab initio quantum calculations are applied to both the parallel and the
      antiparallel arrangements of the beta-sheets of proteins. The energies of the
      NH...O and CH...O hydrogen bonds present in the beta-sheet are evaluated
      separately from one another by appropriate modifications of the model systems.
      The bond energies of these two sorts of hydrogen bonds are found to be very
      nearly equal in the parallel beta-sheet. The NH...O bonds are stronger than
      CH...O in the antiparallel geometry but only by a relatively small margin.
      Moreover, the former NH...O bonds are weakened when placed next to one another,
      as occurs in the antiparallel beta-sheet. As a result, there is little energetic
      distinction between the NH...O and CH...O bonds in the full antiparallel beta
      sheet, just as in the parallel structure.

PMID- 16970499
TI  - How well does Poisson-Boltzmann implicit solvent agree with explicit solvent? A
      quantitative analysis.
AB  - We have quantitatively studied the performance of a finite-difference Poisson
      Boltzmann implicit solvent with respect to the TIP3P explicit solvent in a range
      of systems of biochemical interest. An overall agreement was found between the
      tested implicit and explicit solvents for hydrogen-bonding/salt-bridging dimers
      and peptide monomers and dimers of different conformations and different lengths.
      These comparative analyses also indicate a good transferability of empirically
      optimized parameters for the implicit solvent from small training molecules to
      large testing peptides. However, deviations between the two tested solvents are
      also apparent. Specifically, a consistent deviation was observed when hydrogen
      bonding or salt-bridging dimers are within 4-6 A. The deviation reaches a maximum
      at about 5.5 A, the so-called water-bridging distance. The tested implicit
      solvent, even with optimized parameters, cannot capture the subtle fluctuation in
      the distance-dependent reaction field energy profiles, although smoothed profiles
      can still be obtained and are in overall agreement with those in the explicit
      solvent. Interestingly, the same mechanism underlining the above discrepancy is
      also responsible for the larger deviations of certain peptide conformations, such
      as parallel beta-strand dimers. It is likely that the observed discrepancy may
      cause improper conformational distributions in simulations with the implicit
      solvent when hydrogen-bonding or salt-bridging interactions are crucial, such as
      secondary structure populations in proteins. Validation of the implicit solvent
      with optimized parameters in dynamics simulations will be the next step to study
      the influences of the observed discrepancy at biological conditions.

PMID- 16970500
TI  - Charge delocalization in the special-pair radical cation of mutant reaction
      centers of Rhodobacter sphaeroides from Stark spectra and nonadiabatic spectral
      simulations.
AB  - Stark and absorption spectra for the hole-transfer band of the
      bacteriochlorophyll special pair in the wild-type and L131LH, M160LH, and
      L131LH/M160LH mutants of the bacterial reaction center of Rhodobacter sphaeroides
      are presented, along with extensive analyses based on nonadiabatic spectral
      simulations. Dramatic changes in the Stark spectra are induced by the mutations,
      changes that are readily interpreted in terms of the redox-energy asymmetry and
      degree of charge localization in the special-pair radical cation. The effect of
      mutagenesis on key properties such as the electronic coupling within the special
      pair and the reorganization energy associated with intervalence hole transfer are
      determined for the first time. Results for the L131LH and M160LH/L131LH mutants
      indicate that these species can be considered as influencing the special pair
      primarily through modulation of the redox asymmetry, as is usually
      conceptualized, but M160LH is shown to develop a wide range of effects that can
      be interpreted in terms of significant mutation-induced structural changes in and
      around the special pair. The nonadiabatic spectra simulations are performed using
      both a simple two-state 1-mode and an extensive four-state 70-mode model, which
      includes the descriptions of additional electronic states and explicitly treats
      the major vibrational modes involved. Excellent agreement between the two
      simulation approaches is obtained. The simple model is shown to reproduce key
      features of the Stark effect of the main intervalence transition, while the
      extensive model quantitatively reproduces most features of the observed spectra
      for both the electronic and the phase-phonon regions, thus giving a more
      comprehensive description of the effect of the mutations on the properties of the
      special-pair radical cation. These results for a series of closely related mixed
      valence complexes show that the Stark spectra provide a sensitive indicator for
      the properties of the mixed-valence complexes and should serve as an instructive
      example on the application of nonadiabatic simulations to the study of mixed
      valence complexes in general as well as other chemical systems akin to the
      photosynthetic special pair.

PMID- 16970501
TI  - Adsorption and activity of a domoic acid binding antibody fragment on mesoporous
      silicates.
AB  - The adsorption of an anti-domoic acid single-chain Fv (scFv) antibody fragment
      onto a range of mesoporous silicate supports was investigated. The scFv fragment
      adsorbed to all materials investigated, and pI had an apparently large effect on
      coating, with the greatest-and fastest-adsorption found on the most negatively
      charged silicates. Maximal coating levels attainable did not reflect the pore
      diameters of the materials. The immobilized antibody was functional on all
      materials and bound its antigen, a naturally occurring neurotoxin produced by
      shellfish, in a rapidly saturating manner that suggested the antibody adsorbed in
      a multilayer on the mesoporous particles. The antigen:antibody ratio decreased
      from 1:1.3 to <1:10 with increasing concentration of immobilized antibody, and
      the immobilized scFv exhibited no detectable reduction in domoic acid binding
      over a 42-day incubation period.

PMID- 16970502
TI  - Probing the electronic structure and conformational flexibility of individual
      light-harvesting 3 complexes by optical single-molecule spectroscopy.
AB  - We present fluorescence-excitation spectra of individual light-harvesting 3 (LH3
      or B800-820) complexes of Rhodopseudomonas acidophila at 1.2 K. The optical
      single-molecule studies were employed to investigate the electronic structure as
      well as the conformational flexibility of the individual pigment-protein
      complexes. The optical spectra resemble those of individual light-harvesting 2
      (LH2) complexes, in agreement with the structural similarity of both types of
      complexes. Although variations among the LH3 spectra are large, there is a
      distinct difference in the spectral features of the 800 and 820 nm region that
      appears in all the complexes studied. In the B800 region 4-6 narrow bands are
      present whereas in the B820 region a limited number of relatively broad bands are
      observed. These observations can generally be interpreted in terms of localized
      excitations in the 800 nm region and delocalized excitations in the 820 nm
      region. The observed heterogeneous spectral behavior, especially in the B820
      band, indicates that the B820 pigments of LH3 are sensitive to light-induced
      local conformational changes. It is suggested that a rotation of the C(3)-acetyl
      chain of a BChl a pigment bound to the beta-subunit of the light-harvesting
      complex is the origin of the conformational flexibility and affects the optical
      properties of the whole pigment-protein complex.

PMID- 16970503
TI  - Ruthenium(II) complexes with the mixed ligands 2,2'-bipyridine and 4,4'-dialkyl
      ester-2,2'-bipyridine as pure red dopants for a single-layer
      electrophosphorescent device.
AB  - The mixed-ligand polypyridine ruthenium(II) complexes,
      [Ru(bpy)(2)(dmeb)](2+)(PF(6)(-))(2) (Ru(dmeb)(2+)) and
      [Ru(bpy)(2)(dbeb)](2+)(PF(6)(-))(2) (Ru(dbeb)(2+)), where bpy is bipyridine, dmeb
      is 4,4'-dimethyl ester-2,2'-bipyridine, and dbeb is 4,4'-dibutyl ester-2,2'
      bipyridine, are synthesized and characterized, and their spectroscopic,
      electrochemical, and electroluminescent properties are reported. Both Ru(II)
      complexes showed strong emission from the triplet metal-to-ligand charge-transfer
      excited state, red-shifted emission spectra (lambda(max) = 642 nm), and good
      solubility in organic solvents compared to the frequently used tris(bipyridine)
      Ru(II) complexes. The electrochemical measurements for these Ru complexes showed
      reversible and quasi-reversible redox processes, implying a potential improvement
      in the stability of the electroluminescent device. The electrophosphorescent
      devices were fabricated by doping them in a polymer host using a simple solution
      spin-coating technique. For a single-layer device with the 1.0 wt % Ru(dbeb)(2+)
      doped polymer blends of poly(vinylcarbazole) (PVK) and 2-tert-butylphenyl-5
      biphenyl-1,3,4-oxadiazol (PBD) as the emitting layer and with the metal Ba as the
      cathode, an external quantum efficiency of 3.0%, a luminous efficiency of 2.4
      cd/A, and a maximum brightness of 935 cd/m(2) are reached with an
      electroluminescence (EL) spectral peak at 640 nm and Commission Internationale de
      L'Eclairage chromaticity coordinates of x = 0.64 and y = 0.33, which were
      comparable with standard red color.

PMID- 16970504
TI  - Comment on "Electrooxidation of COad intermediated from methanol oxidation on
      polycrystalline Pt electrode".

PMID- 16970507
TI  - What counts in data mining?

PMID- 16970508
TI  - Atypical antipsychotics for neuropsychiatric symptoms of dementia: malignant or
      maligned?
AB  - Recent concerns regarding the use of atypical antipsychotics when used for the
      treatment of neuropsychiatric symptoms in dementia have led to a flurry of
      studies attempting to re-evaluate their place in therapy. We critically review
      current evidence on the safety profiles of these agents in patients with
      behavioural and psychological symptoms of dementia (BPSD) and provide
      recommendations to guide the clinician. Potential risks with this class of
      medications include extrapyramidal symptoms (EPS), weight gain, diabetes
      mellitus, cardiac conduction abnormalities (e.g. corrected QT [QTc] interval
      prolongation), cerebrovascular adverse events and mortality. Compared with
      placebo, treatment of BPSD with atypical antipsychotics leads to little or no
      increase in EPS and no significant weight change. Compared with typical
      antipsychotics, treatment of BPSD with atypical antipsychotics leads to a reduced
      risk of EPS, lower incidences of tardive dyskinesias and no significant weight
      gain. Atypical antipsychotics have not been associated with glucose intolerance,
      diabetes or hyperlipidaemia in elderly dementia patients. Both typical and
      atypical antipsychotics have been associated with cardiac conduction
      abnormalities, with the magnitude of QTc prolongation being slightly smaller with
      atypical antipsychotics. Randomised controlled trials suggest that atypical
      antipsychotics are associated with an increased risk of cerebrovascular adverse
      events, such as stroke, and an increased mortality compared with placebo.
      However, it appears that typical antipsychotics have similar risks of
      cerebrovascular adverse events and death. An increased risk of anticholinergic
      adverse effects and falls must also be considered with both typical and atypical
      antipsychotics. In summary, atypical antipsychotics are associated with
      potentially serious adverse events. Before prescribing these medications in
      elderly dementia patients, baseline EPS, ECG abnormalities and concomitant
      medications should be assessed, and the presence of cardiovascular,
      cerebrovascular and metabolic risk factors should be taken into consideration
      when benefits and risks are being weighed.

PMID- 16970509
TI  - Disease-modifying antirheumatic drugs in pregnancy: current status and
      implications for the future.
AB  - Drug use during pregnancy is sometimes unavoidable, especially in chronic
      inflammatory diseases such as rheumatoid arthritis (RA). The use of disease
      modifying antirheumatic drugs (DMARDs) often starts in the early stage of RA;
      therefore, women of reproductive age are at risk for exposure to a DMARD at time
      of conception as well as during pregnancy. The aim of this paper was to review
      recent literature about DMARDs used for rheumatic diseases in pregnancy and to
      describe the type of study designs and results reported.Twenty-nine studies;
      eight on hydroxychloroquine/chloroquine, thirteen on methotrexate, three on
      sulfasalazine and six on azathioprine were identified. With respect to
      hydroxychloroquine, most studies concluded that it could be safely used in
      systemic lupus erythematosus or RA. The same conclusions were drawn from the
      azathioprine studies, but the available evidence is scarce. Although the evidence
      regarding the safety of methotrexate during pregnancy is conflicting, a high rate
      of pregnancy losses indicates a risk to the fetus. For each individual case it
      must be decided whether the benefits outweigh the potential risks. No major
      teratogenic effects of sulfasalazine were seen although teratogenic effects still
      can not be excluded. For all other DMARDs, the information on their use in
      pregnancy was limited. This review underscores the gross absence of data on
      safety and risks of DMARD use during conception and pregnancy. While young women
      use these drugs in pregnancy, this review stresses the importance of good
      monitoring and further research.

PMID- 16970511
TI  - Comparative performance of two quantitative safety signalling methods:
      implications for use in a pharmacovigilance department.
AB  - BACKGROUND AND OBJECTIVES: There is increasing interest in using
      disproportionality-based signal detection methods to support postmarketing safety
      surveillance activities. Two commonly used methods, empirical Bayes multi-item
      gamma Poisson shrinker (MGPS) and proportional reporting ratio (PRR), perform
      differently with respect to the number and types of signals detected. The goal of
      this study was to compare and analyse the performance characteristics of these
      two methods, to understand why they differ and to consider the practical
      implications of these differences for a large, industry-based pharmacovigilance
      department. METHODS: We compared the numbers and types of signals of
      disproportionate reporting (SDRs) obtained with MGPS and PRR using two
      postmarketing safety databases and a simulated database. We recorded signal
      counts and performed a qualitative comparison of the drug-event combinations
      signalled by the two methods as well as a sensitivity analysis to better
      understand how the thresholds commonly used for these methods impact their
      performance. RESULTS: PRR detected more SDRs than MGPS. We observed that MGPS is
      less subject to confounding by demographic factors because it employs
      stratification and is more stable than PRR when report counts are low. Simulation
      experiments performed using published empirical thresholds demonstrated that PRR
      detected false-positive signals at a rate of 1.1%, while MGPS did not detect any
      statistical false positives. In an attempt to separate the effect of choice of
      signal threshold from more fundamental methodological differences, we performed a
      series of experiments in which we modified the conventional threshold values for
      each method so that each method detected the same number of SDRs for the example
      drugs studied. This analysis, which provided quantitative examples of the
      relationship between the published thresholds for the two methods, demonstrates
      that the signalling criterion published for PRR has a higher signalling frequency
      than that published for MGPS. DISCUSSION AND CONCLUSION: The performance
      differences between the PRR and MGPS methods are related to (i) greater
      confounding by demographic factors with PRR; (ii) a higher tendency of PRR to
      detect false-positive signals when the number of reports is small; and (iii) the
      conventional thresholds that have been adapted for each method. PRR tends to be
      more 'sensitive' and less 'specific' than MGPS. A high-specificity
      disproportionality method, when used in conjunction with medical triage and
      investigation of critical medical events, may provide an efficient and robust
      approach to applying quantitative methods in routine postmarketing
      pharmacovigilance.

PMID- 16970510
TI  - Neuropsychiatric complications of antiretroviral therapy.
AB  - Neuropsychiatric adverse effects related to potent antiretroviral therapy are
      among the complications that can lead to poor adherence, treatment interruptions,
      or change of antiretroviral therapy regimens. For a historical perspective, we
      review early literature and case reports with CNS adverse effects attributed to
      antiretrovirals. The variability of the cerebrospinal fluid penetration of
      individual antiretrovirals may contribute to their potential for behavioural and
      psychiatric manifestations. The majority of neuropsychiatric complications
      related to potent antiretroviral therapy have been associated with the use of the
      efavirenz. Updates on the risk of neuropsychiatric manifestations with efavirenz
      use in patients with a history of psychiatric disorders or substance abuse are
      reviewed. We include a critical review of recently published data on the long
      term CNS adverse effects with efavirenz. Special attention is given to the
      results of recent investigations on the relationship between the pharmacogenomics
      of genes responsible for efavirenz metabolism and the plasma concentration of
      efavirenz. It is important to note that there is no established direct
      correlation of efavirenz concentrations and symptoms. It is not recommended for
      practitioners to adjust efavirenz doses in order to prevent or alleviate CNS
      adverse effects. Patients may be placed at risk for virological failure and
      resistance if they receive suboptimal doses of efavirenz. The aim of this article
      is to give a concise review and an update on recent literature concerning
      neuropsychiatric effects of antiretroviral use in HIV-infected patients. Our
      intent is to present practitioners with data that can be used in a practical way
      to both educate and improve outcomes in the HIV-infected patient population.

PMID- 16970512
TI  - Evidence of tendinitis provoked by fluoroquinolone treatment: a case-control
      study.
AB  - OBJECTIVE: To investigate the association between the use of fluoroquinolone
      agents and the risk of tendinitis in a large population-based case-control study.
      METHODS: The study was performed by linking automated health databases from the
      Region of Lombardia, Italy. Cases were patients aged > or =18 years who had a
      hospital discharge diagnosis of non-traumatic tendinitis in 2002-3. For each
      case, up to five controls were randomly selected among those eligible for
      inclusion in the study. A conditional logistic regression model was used to
      estimate the odds ratio of tendinitis associated with the current, recent and
      past use of fluoroquinolones. Odds ratios were adjusted for exposure to other
      antibacterials and other drugs. RESULTS: 22,194 cases and 104,906 controls met
      the inclusion criteria. Current use of fluoroquinolones significantly increased
      the risk of tendon disorders as a whole (odds ratio [OR] = 1.7; 95% CI 1.4, 2.0),
      tendon rupture (OR = 1.3; 95% CI 1.0, 1.8) and rupture of the Achilles' tendon
      (OR = 4.1; 95% CI 1.8, 9.6). Concomitant use of corticosteroids and
      fluoroquinolones increased the risk of both tendon rupture (OR = 3.1; 95% CI 1.5,
      6.3) and rupture of the Achilles' tendon (OR = 43.2; 95% CI 5.5, 341.1).
      DISCUSSION: Evidence that exposure to fluoroquinolones is associated with the
      sudden occurrence of tendinitis is supported by this large population-based
      study. We can estimate that a single case of rupture of the Achilles' tendon
      would occur for every 5958 persons treated with fluoroquinolones (95% CI 2148,
      23,085). The corresponding number needed to harm is 979 (95% CI 122, 9172) for
      patients who concomitantly use corticosteroids and 1638 (95% CI 351, 8843) for
      those aged >60 years. CONCLUSION: Clinicians should be aware of this adverse
      effect, and the increased risk for fluoroquinolone-associated tendinitis in
      elderly patients with corticosteroid use must be considered when these agents are
      prescribed.

PMID- 16970515
TI  - Constructing an autistic identity: AS voices online.
AB  - Excerpts from current research with people who have autism using online
      discussion groups are provided. Two major themes emerged that focus on "expert"
      knowledge of autism and identity. In contrast to the image of people with autism
      being unable to speak for themselves, our research on chat rooms has demonstrated
      that these individuals are finding a voice in an online environment, and the
      Internet may be a powerful tool in enabling this voice to be heard. The challenge
      that experiential knowledge poses to scientific knowledge is discussed in light
      of diagnosis, and the positive nature of an autism spectrum (AS) identity is
      highlighted as a common thread in discussions.

PMID- 16970513
TI  - Comparison of the risk of drowsiness and sedation between levocetirizine and
      desloratadine: a prescription-event monitoring study in England.
AB  - BACKGROUND AND OBJECTIVES: Desloratadine and levocetirizine are histamine H(1)
      receptor antagonists (antihistamines) that were launched in the UK in 2001. Our
      objective was to compare the frequency with which drowsiness and sedation were
      reported for desloratadine and levocetirizine within the first 30 days of
      observation, as monitored using the observational cohort technique of
      prescription-event monitoring (PEM). METHODS: Exposure data were derived from
      dispensed prescriptions written by primary care physicians and outcome data were
      derived from questionnaires that were posted to prescribers at least 6 months
      after the date of the first prescription for each patient. The odds ratio (OR)
      was calculated using unconditional logistic regression modelling. The effect of
      age, sex, reported prescribing indication (allergic rhinitis with
      asthma/wheezing, allergic rhinitis without asthma/wheezing, 'other'), pattern of
      use and reported previous antihistamine use on the OR was examined. A time-to
      event analysis was performed. RESULTS: The cohorts comprised >24,000 patients in
      total. Cohort demographics were similar (both cohorts: median age 37 years; 60%
      women); the most frequently reported prescribing indication for both drugs was
      allergic rhinitis without asthma/wheezing (54%). The incidence of first reports
      of drowsiness/sedation for levocetirizine or desloratadine was low (46 [0.37%]
      and 9 [0.08%], respectively) and statistically different (p < 0.0001). These
      events tended to occur earlier for desloratadine than levocetirizine (50% at 7 or
      14 days of observation, respectively; p = 0.6487), but the cumulative time to
      event differed, with more events observed for levocetirizine than expected (p <
      0.0001; 46 vs 28.09). The final estimates of risk were the sex-adjusted ORs for
      each prescribing indication category: allergic rhinitis with asthma/wheezing
      (3.51; 95% CI 0.71, 17.43; n = 3357), allergic rhinitis without asthma/wheezing
      (6.75; 95% CI 2.37, 19.22; n = 12,627) and 'other' (3.11; 95% CI 0.86, 11.31; n =
      6725). DISCUSSION: Although the reporting rates of drowsiness and sedation are
      low for both drugs, patients prescribed levocetirizine are more likely to
      experience drowsiness and sedation in the first month of observation (after
      starting treatment) than patients prescribed desloratadine. For patients with
      allergic rhinitis without asthma/wheezing, the sex-adjusted odds of
      drowsiness/sedation were over six times greater in patients using levocetirizine
      than desloratadine in the first month of observation, with the OR being
      statistically significant. For the other two indication categories, allergic
      rhinitis with asthma/wheezing and 'other', the OR was not statistically
      significant. CONCLUSIONS: Although the risk of drowsiness/sedation is low,
      conditions such as allergic rhinitis are common, which makes any impact on
      patient cognitive function important. Doctors should be aware of this when
      prescribing these products to patients where daytime sedation is undesirable.
      However, essential components of the comparative benefit-risk evaluation of these
      two products include assessment of efficacy and patient preference (neither of
      which forms part of this study).

PMID- 16970516
TI  - Producing decisions in service-user groups for people with an intellectual
      disability: two contrasting facilitator styles.
AB  - Service-user groups whose goals include the promotion of self-advocacy for people
      with an intellectual disability aim, among other things, to encourage service
      users to identify problems and find solutions. However, service users'
      contributions to group sessions may not always be full and spontaneous. This
      presents a dilemma to the facilitator. In two case studies, we identify two ways
      in which the dilemma is managed. In one case, the facilitator takes an initiating
      role in each stage of a decision-making cycle. In the other, the facilitator
      short-circuits the decision-making cycle. The former seems to be closer to the
      philosophy of self-advocacy, but both nevertheless result in clients not taking
      the initiative and arguably disempowers them.

PMID- 16970517
TI  - Inclusion at a university: experiences of a young woman with Down syndrome.
AB  - For young adults with developmental disabilities, postsecondary experiences on a
      university campus with same-age peers can provide opportunities for learning and
      social integration. Through the collaborative support of university instructors,
      a preservice teacher, and her mother, a young woman with Down syndrome was
      successfully included in a speech communications course at a 4-year, private
      university. Our purpose here was to explore the impact of this experience on the
      student, her classmates, and preservice teacher who offered peer support. The
      experience provided opportunities for interaction with age-appropriate peers and
      was a positive learning experience for all participants. Challenges emerged
      related to assessment, expectations, and building relationships. Implications for
      potential inclusive transition opportunities at the university were discussed.

PMID- 16970518
TI  - The Hissom closure in Oklahoma: errors and interpretation problems in Conroy et
      al. (2003).
AB  - We reviewed a Mental Retardation article by Conroy et al. (2003) on consumer
      outcomes following the closure of the Hissom Center in Oklahoma. In this article
      the authors misconstrued their 254 subjects, implying they are representative of
      the Hissom Focus Class while failing to account for 128 subjects included in an
      earlier analysis. We found the research to be seriously compromised by data
      collection problems and discrepancies between reported findings and those
      obtained when the analyses were replicated. Problems ranged from those that
      seriously compromise the findings (such as the sample) to other problems in basic
      data management, transcription, and analysis that, when taken together,
      compromise the integrity of the findings, lead to inappropriate interpretations,
      and give rise to misleading conclusions that do not follow from the data.

PMID- 16970520
TI  - Lessons drawn from the critique of the Hissom closure evaluation.

PMID- 16970521
TI  - Both accurate interpretation of deinstitutionalization and a postinstitutional
      research agenda are needed.

PMID- 16970522
TI  - President's Address 2006 creating sustainable reform: aligning our generational
      prisms.

PMID- 16970523
TI  - Increases in recipients of and expenditures for Medicaid home and community based
      services continued in 2005.

PMID- 16970526
TI  - On evidence-based orthodontics.

PMID- 16970527
TI  - Integrating ear and scalp acupuncture techniques into the care of blast-injured
      United States military service members with limb loss.

PMID- 16970528
TI  - The debate within integrative medicine.

PMID- 16970529
TI  - Yin/Yang polarization: quantitative diagnostic evaluation using biophoton
      measurement from human hands and feet.

PMID- 16970530
TI  - Exceptional disease courses after the use of CAM: selection, registration,
      medical assessment, and research. an international perspective.
AB  - OBJECTIVES: To describe the different approaches that investigators in several
      countries have used to obtain, register, assess, and research exceptional case
      histories after the use of complementary and alternative medicine (CAM). METHODS:
      Searches have been carried out currently in the databases PubMed and MEDLINE((R))
      using the keywords: exceptional disease course/best and worst cases/best-case
      series + use of CAM. We have only found a few papers limited to best-case series
      and cancer. Furthermore, we have used the "snowball method" by contacting
      researchers in different countries starting with with the National Cancer
      Institute in the United States in order to get information about ongoing
      approaches to obtain, register, assess, and research exceptional case histories
      after the use of CAM. RESULTS: There appears to be a gap between "evidence-based"
      knowledge drawn from randomized controlled trials, systematic reviews, and meta
      analyses and experience-based knowledge of treatment outcomes reported by
      patients and CAM providers. Several research groups in different countries have
      initiated studies on patients experiencing exceptional treatment outcomes after
      the use of CAM. Four different approaches to collecting and assessing such case
      histories have been identified. Three of the approaches collect histories from
      the treatment providers, whereas the fourth recruits case histories mainly from
      patients themselves. The medical assessments are generally similar, and seek to
      document whether the course of disease is different than would have been expected
      in a conventional treatment situation. CONCLUSIONS: Given differences in the
      current procedures, the establishment of an international formal collaboration
      for the recruitment, assessment, and study of exceptional patients is likely to
      take time. Comparative studies may, however, generate new knowledge about
      exceptional disease courses across disease categories, cultural contexts, and
      national boundaries. Our recommendations are that therapeutic approaches that
      show promising results should warrant prospective study and randomized clinical
      trials. In addition we recommend that there be (1) agreement on the definition of
      an exceptional patient, (2) agreement on the interpretation of treatment results,
      (3) agreement on content requirements of medical records, (4) more consideration
      of worst cases, (5) more international exchange of experience with registration
      procedures, and (6) more international exchange of experience with medical
      assessment procedures.

PMID- 16970531
TI  - Changes in FMRI in the human brain related to different durations of manual
      acupuncture needling.
AB  - OBJECTIVES: The present study is aimed at evaluating the effects of manual
      acupuncture with different durations on the human brain using functional magnetic
      resonance imaging. MATERIALS AND METHODS: Eighteen healthy right-handed
      volunteers were divided into three groups randomly. Each group received only one
      kind of acupuncture on the right LI4 (Hegu) point, which lasted 30 sec, 60 sec,
      or 180 sec, respectively. Fix-effect and conjunction analysis were used to
      compare the effects of the three kinds of acupunctures. RESULTS: The results
      indicated that the stimulation of manual acupuncture with different durations
      could induce different effects in the central nervous system on the human brain.
      The longer duration of manual acupuncture might induce more significant areas.
      CONCLUSIONS: The present study provided not only neuroimaging evidence for manual
      acupuncture, but also a useful guide for clinical applications of acupuncture. In
      addition, the results might be helpful to understand the relationship between the
      central nervous system responses and the durations of acupuncture.

PMID- 16970532
TI  - The effect of Johrei healing on substance abuse recovery: a pilot study.
AB  - OBJECTIVE: The purpose of the present study was to determine the effectiveness of
      Johrei healing, a form of energy healing, on substance use and psychologic
      symptoms in a sample of clients receiving substance abuse treatment. METHODS:
      Twenty-one (21) persons in residential substance-abuse treatment participated in
      a randomized, wait-list control pilot study of Johrei healing. Twelve (12) of the
      participants received three 20-minute Johrei sessions for 5 weeks in addition to
      their regular treatment. RESULTS: The results are from the first treatment wave.
      Individual healing sessions were evaluated pre-post with the Johrei Experience
      Scale. Participants showed significant decreases in stress/depression and
      physical pain and increases in positive emotional/spiritual state, energy, and
      overall well-being after an individual Johrei healing session. The Global
      Assessment of Individual Need (GAIN), Profile of Mood States (POMS), General
      Alcoholics Anonymous Tools of Recovery, and 12-Step Participation scales were
      administered before and after the 5-week intervention to assess change in
      substance use, psychologic distress, mood, and 12-Step participation.
      Improvements in depression and trauma symptoms, externalizing behaviors (GAIN),
      and vigor (POMS) were found for the treatment group. Despite comparable 12-Step
      attendance the treatment group showed greater improvement than the wait-list
      control group in the use of 12-Step recovery tools. No difference in substance
      use was found between the two groups. CONCLUSIONS: Variables related to substance
      use and relapse showed improvement in the treatment group suggesting that Johrei
      healing shows promise and should be studied with a larger sample, over a longer
      treatment period, with sham controls.

PMID- 16970533
TI  - Acupuncture needle sensations associated with De Qi: a classification based on
      experts' ratings.
AB  - BACKGROUND: Many English language words have been used to describe the
      acupuncture needle sensation known as de qi, words such as dull, aching, and
      spreading. However, there is little agreement on which actual words are
      acceptable as descriptors. In experimental trials of acupuncture in which the
      needle sensation is an important variable, a quantitative measure is needed to
      monitor and control for variability in de qi. METHODS: An established scale in
      the literature provides a list of 25 sensations associated with acupuncture
      needling that patients might experience. An international group of acupuncture
      experts rated these 25 sensations in two categories: those predominantly
      associated with de qi and those with acute pain at the site of needling. For each
      category, sensations were classified into hierarchic clusters, one for de qi and
      one for acute pain, and the results were presented in dendrograms. RESULTS:
      Twenty-nine international experts were invited to participate; 22 (76%) responded
      and 20 completed the questionnaire. On average, they had 21 years' experience in
      acupuncture practice (range 10-30 years). Seven sensations were found to be in
      the cluster associated with de qi: aching, dull, heavy, numb, radiating,
      spreading, and tingling. Nine sensations were found to be in a cluster associated
      with acute pain at the site of needling: burning, hot, hurting, pinching,
      pricking, sharp, shocking, stinging, and tender. The experts also raised a number
      of issues regarding the limitations of the questionnaire used, providing useful
      data for future research. CONCLUSIONS: Data from experienced acupuncturists have
      been analyzed to provide two separate clusters of sensations associated with
      acupuncture needling: a de qi cluster and an acute pain cluster. In the design of
      experimental trials involving acupuncture needling, researchers will find these
      two clusters of sensations useful for monitoring and controlling for variation in
      needle sensation.

PMID- 16970534
TI  - Acupuncture use in the United States: findings from the National Health Interview
      Survey.
AB  - OBJECTIVE: Acupuncture has become an important provider-based complementary and
      alternative medicine (CAM) treatment. To improve understanding of its role in
      personal health care, an analysis of national data was conducted to examine user
      sociodemographics, conditions treated, and the relationship of use with
      conventional Western medical care. DESIGN: A nationally representative cross
      sectional survey. SETTING: The 2002 National Health Interview Survey (NHIS),
      conducted in all 50 states and the District of Columbia. PARTICIPANTS: Thirty-one
      thousand and forty-four (31,044) adults who completed the NHIS Sample Adult Core.
      OUTCOME MEASURES: The primary outcome measure was recent use of acupuncture,
      defined as use within the previous 12 months. RESULTS: In the 2002 NHIS sample,
      4.1% of the respondents reported lifetime use, and 1.1% (representing 2.13
      million Americans) reported recent use of acupuncture. Recent use (n = 327) was
      positively associated with being an Asian female, living in the West or
      Northeast, having poorer self-reported health status, a higher level of
      education, and being an ex-smoker. Among recent users, the most typical treatment
      regimen was two to four treatments (34.5%), with musculoskeletal complaints being
      the most frequently reported conditions, led by back pain (34.0%). Reports of
      perceived benefit were generally high. Respondents indicated that acupuncture was
      used both as an alternative and as a complementary therapy. A reasonable number
      also reported being referred to acupuncture by a conventional medical
      professional (25.3%). The cross-sectional nature of the data precluded analysis
      of transitions in health care use (between conventional and CAM treatments) over
      time. CONCLUSIONS: Utilization of acupuncture was somewhat lower than expected
      given its significant national and international recognition and its visibility
      in the media. This may in part be a function of provider availability and
      cultural factors.

PMID- 16970535
TI  - Interventions and physician characteristics in a randomized multicenter trial of
      acupuncture in patients with low-back pain.
AB  - OBJECTIVE: Descriptions of the interventions used in acupuncture studies are
      often incomplete. The aim of this paper is to describe participating trial
      physicians and interventions in a randomised trial of acupuncture for low back
      pain. DESIGN: Three-armed, randomized, controlled multicenter trial with 1-year
      follow-up. A total of 301 patients with low-back pain were randomized to 12
      sessions of semistandardized acupuncture (at least six local and two distant
      points needled bilaterally from a selection of predefined points, but individual
      choice of additional body or ear acupuncture points possible), minimal
      acupuncture (superficial needling of at least 6 of 10 predefined, bilateral,
      distant nonacupuncture points), or a waiting list control (2 months no
      acupuncture followed by semistandardised acupuncture described above). OUTCOME
      MEASURES: Participating trial physicians and interventions. RESULTS: Forty-five
      (45) physicians specializing in acupuncture (mean age 44 +/- 7.8 years, 23 (51%)
      female) in 30 outpatient centers in Germany provided the interventions. The
      median duration of acupuncture training of trial physicians was 350 hours (range
      140-2508). The most frequently reported Chinese diagnosis was Kidney deficiency
      (39%), followed by qi and Blood stagnation (24%), and bi syndrome (20%). The
      total number of needles used was 17.3 +/- 4.2 in the acupuncture group compared
      to 12.3 +/- 1.2 in the minimal acupuncture group. In total, 40 physicians (89%)
      stated that they would have treated patients similarly or in exactly the same way
      outside of the trial, whereas 5 (11%) stated that they would have treated
      patients differently. CONCLUSIONS: For most trial physicians, the
      semistandardized acupuncture strategy used in this trial was an acceptable
      compromise for an efficacy study. However, a relevant minority of participating
      trial physicians stated that they would have treated patients differently outside
      of the trial.

PMID- 16970536
TI  - One-year follow-up of a randomized clinical trial comparing flexion distraction
      with an exercise program for chronic low-back pain.
AB  - OBJECTIVE: Flexion distraction is a commonly used form of chiropractic care with
      chiropractor utilization rates of 58%. However, no previous randomized clinical
      trial has assessed the effectiveness of this form of care. The objective of this
      investigation was to compare the pain and disability during the year after active
      care based on treatment group allocation (Flexion Distraction versus Exercise
      Program). STUDY DESIGN: Randomized clinical trial, follow-up. SUBJECTS: Two
      hundred and thirty-five (235) subjects who were previously randomized to either
      chiropractic care (flexion distraction) or physical therapy (exercise program)
      within a clinical trial. OUTCOME MEASURES: Subjects were followed for 1 year via
      mailed questionnaires to assess levels of pain (Visual Analog Scale) and
      dysfunction (Roland Morris). RESULTS: Study subjects had a decrease in pain and
      disability after intervention regardless of which group they attended (p <
      0.002), however, during the year after care, subjects who received chiropractic
      care (flexion distraction therapy) had significantly lower pain scores than
      subjects who received physical therapy (exercise program) (p = 0.02).
      CONCLUSIONS: In this first trial on flexion distraction care, flexion distraction
      was found to be more effective in reducing pain for 1 year when compared to a
      form of physical therapy.

PMID- 16970537
TI  - Gargling with tea catechin extracts for the prevention of influenza infection in
      elderly nursing home residents: a prospective clinical study.
AB  - OBJECTIVES: To evaluate the effects of gargling tea catechin extracts on the
      prevention of influenza infection in elderly nursing home residents. DESIGN: A
      prospective study conducted for 3 months from January to March 2005.
      SETTINGS/LOCATION: A nursing home in Japan. SUBJECTS: A total of 124 elderly
      residents of at least 65 years of age were enrolled in the study. Seventy-six
      residents (83 +/-8.2 years, mean +/-standard deviation; 24 men, 52 women) gargled
      with tea catechin extract (catechin group) and were compared with 48 age- and sex
      matched residents who gargled without tea catechin extracts (control group). All
      the residents were vaccinated with an influenza vaccine until early December
      2004. INTERVENTIONS: catechin group: gargling with the tea catechin extract
      solution (200 microg/mL catechins, 60% of catechins comprise epigallocatechin
      gallate); control group: gargling without the catechin extract solution. In both
      groups, gargling was performed three times daily for 3 months. OUTCOME MEASURES:
      The incidence of influenza infection during the study was compared between the
      two groups. A safety evaluation was conducted to observe adverse events during
      the study. RESULTS: The incidence of influenza infection was significantly lower
      in the catechin group (1.3%, one resident) than in the control group (10%, five
      residents) calculated by multivariate logistic regression analysis (p = 0.028;
      odds ratio, 15.711; 95% confidence interval, 1.883-399.658). No adverse events,
      such as respiratory tract irritation, an obstruction, or allergic bronchial
      spasm, were observed during the study. CONCLUSIONS: This prospective study
      demonstrating the effect of catechin gargling on the prevention of influenza
      infection in the elderly is the first to be reported in the literature. Further
      randomized, controlled studies are needed to confirm the effects of catechin
      gargling on the prevention of influenza infection.

PMID- 16970538
TI  - Traditional chinese medicine treatment of epilepsy.
AB  - OBJECTIVES: To evaluate the effectiveness of traditional Chinese medicine,
      specifically the traditional herbal formulation Bu-yang-huan-wu-tang, for
      treating epilepsy stemming from cerebrovascular dysfunction. SUBJECTS: Three
      adult patients with epilepsy refractory to standard antiepileptic medications
      were involved. RESULTS: All three showed substantial improvement in the frequency
      and severity of seizures after Bu-yanghuan- wu-tang was added to conventional
      medical treatment. CONCLUSIONS: Decrease of seizure frequency and severity in
      three epileptic patients was achieved by adding Bu-yang-huan-wu-tang to
      conventional therapy according to the principles of Traditional Chinese Medicine
      (TCM) theory. This treatment mainly relied on the resolution of blood stagnation
      in cerebrovascular systems. Blood stagnation is an important underlying pathology
      of many disease processes according to TCM theory.

PMID- 16970539
TI  - Challenging the new orthodoxy in integrative medicine.
AB  - This paper offers a critique of the paradigm adopted in integrative medicine.
      Several concerns are raised in relation to this paradigm, including the absence
      of any explicit and well-defined criteria for appropriate therapeutic selection
      or referral, inherent biases, and the significantly reduced clinical efficacy of
      the traditional and alternative therapies utilized. In particular, the obvious
      lack of a clear and cogent theoretical model for integration is noted. The
      central features of existing models in world medicine are outlined, and the
      requirements for a universal model are discussed in relation to its capacity to
      address the specific concerns are raised. To develop this model fully, the need
      to reopen critical debate on the nature of medicine, and for rigorous model
      testing and peer review, are noted and the challenge to do so is delivered.

PMID- 16970540
TI  - On chemical medicine, thermodynamics, and homeopathy.
AB  - The author indicates why homeopathic medicine is an example of future information
      medicine, a member of the more general psychophysiologic medicine group. Using
      standard chemical thermodynamics, it is readily shown that the driving force for
      all chemical reactions involves the logarithm of chemical activities for the
      different species involved. Because chemical activity is given by the product of
      concentration and thermodynamic activity coefficient, such reaction driving
      forces involve the sum of ln gamma ( j ) and ln c(j) for the j-species.
      Homeopathy involves the dilution of cj and succussion, which can increase gamma
      (j) ; thus, when c(j) goes to the ultradilution state, the thermodynamic driving
      force for change does not disappear as is assumed by many and, in fact, can even
      increase through the ln gamma ( j ) terms. Going to a more complex reference
      frame for viewing nature, one can, at least, qualitatively show how oscillating
      and decaying properties in time can occur for homeopathic remedies.

PMID- 16970541
TI  - Training in and use of diagnostic techniques among CAM practitioners: an
      Australian study.
AB  - OBJECTIVES: This study aimed to determine the extent to which complementary and
      alternative medicine (CAM) practitioners in Australia are trained in and use CAM
      and Western medical diagnostic techniques, and the influence this may have on
      their role as primary contact practitioners. DESIGN: A 45-item questionnaire was
      mailed to members of the Australian Natural Therapists' Association and the
      Australian Traditional Medicine Society. RESULTS: We received 617 responses
      (22%). Respondents reported high frequency of training in and use of Western case
      history taking, observation, taking blood pressure and pulses, palpation,
      postural assessment, orthopaedic testing, in addition to naturopathic case
      history taking, iris diagnosis, and face, tongue, and nail diagnosis. We found a
      significant relationship between the confidence practitioners had in identifying
      clients requiring referral and their training in these areas. CONCLUSIONS:
      Despite the reported high frequency of training in and use of Western medical and
      CAM diagnostic techniques, 32% of respondents reported a lack of confidence in
      identifying patients requiring referral. This could compromise the safety of
      clients and the effectiveness of practice.

PMID- 16970542
TI  - Diagnostic accuracy among the allied health professions: commentary on Grace et
      Al.

PMID- 16970545
TI  - Aldo-keto reductases and bioactivation/detoxication.
AB  - Aldo-keto reductases (AKRs) are soluble NAD(P)(H) oxidoreductases that primarily
      reduce aldehydes and ketones to primary and secondary alcohols, respectively. The
      ten known human AKR enzymes can turnover a vast range of substrates, including
      drugs, carcinogens, and reactive aldehydes. They play central roles in the
      metabolism of these agents, and this can lead to either their bioactivation or
      detoxication. AKRs are Phase I drug metabolizing enzymes for a variety of
      carbonyl-containing drugs and are implicated in cancer chemotherapeutic drug
      resistance. They are involved in tobacco-carcinogenesis because they activate
      polycyclic aromatic trans-dihydrodiols to yield reactive and redox active o
      quinones, but they also catalyze the detoxication of nicotine derived nitrosamino
      ketones. They also detoxify reactive aldehydes formed from exogenous toxicants,
      e.g., aflatoxin, endogenous toxicants, and those formed from the breakdown of
      lipid peroxides. AKRs are stress-regulated genes and play a central role in the
      cellular response to osmotic, electrophilic, and oxidative stress.

PMID- 16970546
TI  - Interactions between substrates and the haem-bound nitric oxide of ferric and
      ferrous bacterial nitric oxide synthases.
AB  - We report here the resonance Raman spectra of the FeIII-NO and FeII-NO complexes
      of the bacterial NOSs (nitric oxide synthases) from Staphylococcus aureus and
      Bacillus subtilis. The haem-NO complexes of these bacterial NOSs displayed Fe-N-O
      frequencies similar to those of the mammalian NOSs, in presence and absence of L
      arginine, indicating that haem-bound NO and L-arginine had similar haem
      environments in bacterial and mammalian NOSs. The only notable difference between
      the two types of NOS was the lack of change in Fe-N-O frequencies of the FeIII-NO
      complexes upon (6R) 5,6,7,8-tetrahydro-L-biopterin binding to bacterial NOSs. We
      report, for the first time, the characterization of NO complexes with NOHA
      (N(omega)-hydroxy-L-arginine), the substrate used in the second half of the
      catalytic cycle of NOSs. In the FeIII-NO complexes, both L-arginine and NOHA
      induced the Fe-N-O bending mode at nearly the same frequency as a result of a
      steric interaction between the substrates and the haem-bound NO. However, in the
      FeII-NO complexes, the Fe-N-O bending mode was not observed and the nu(Fe-NO)
      mode displayed a 5 cm(-1) higher frequency in the complex with NOHA than in the
      complex with L-arginine as a result of direct interactions that probably involve
      hydrogen bonds. The different behaviour of the substrates in the FeII-NO
      complexes thus reveal that the interactions between haem-bound NO and the
      substrates are finely tuned by the geometry of the Fe-ligand structure and are
      relevant to the use of the FeII-NO complex as a model of the oxygenated complex
      of NOSs.

PMID- 16970547
TI  - Characterization of binding sites of eukaryotic transcription factors.
AB  - To explore the nature of eukaryotic transcription factor (TF) binding sites and
      determine how they differ from surrounding DNA sequences, we examined four
      features associated with DNA-binding sites: G+C content, pattern complexity,
      palindromic structure, and Markov sequence ordering. Our analysis of the
      regulatory motifs obtained from the TRANSFAC database, using yeast intergenic
      sequences as background, revealed that these four features show variable
      enrichment in motif sequences. For example, motif sequences were more likely to
      have palindromic structure than were background sequences. In addition, these
      features were tightly localized to the regulatory motifs, indicating that they
      are a property of the motif sequences themselves and are not shared by the
      general promoter "environment" in which the regulatory motifs reside. By breaking
      down the motif sequences according to the TF classes to which they bind, more
      specific associations were identified. Finally, we found that some correlations,
      such as G+C content enrichment, were species-specific, while others, such as
      complexity enrichment, were universal across the species examined. The
      quantitative analysis provided here should increase our understanding of protein
      DNA interactions and also help facilitate the discovery of regulatory motifs
      through bioinformatics.

PMID- 16970548
TI  - Topological properties of protein-protein and metabolic interaction networks of
      Drosophila melanogaster.
AB  - The underlying principle governing the natural phenomena of life is one of the
      critical issues receiving due importance in recent years. A key feature of the
      scale-free architecture is the vitality of the most connected nodes (hubs). The
      major objective of this article was to analyze the protein-protein and metabolic
      interaction networks of Drosophila melanogaster by considering the architectural
      patterns and the consequence of removal of hubs on the topological parameter of
      the two interaction systems. Analysis showed that both interaction networks
      follow a scale-free model, establishing the fact that most real world networks,
      from varied situations, conform to the small world pattern. The average path
      length showed a two-fold and a three-fold increase (changing from 9.42 to 20.93
      and from 5.29 to 17.75, respectively) for the protein-protein and metabolic
      interaction networks, respectively, due to the deletion of hubs. On the contrary,
      the arbitrary elimination of nodes did not show any remarkable disparity in the
      topological parameter of the protein-protein and metabolic interaction networks
      (average path length: 9.42+/-0.02 and 5.27+/-0.01, respectively). This aberrant
      behavior for the two cases underscores the significance of the most linked nodes
      to the natural topology of the networks.

PMID- 16970549
TI  - Normalization using weighted negative second order exponential error functions
      (NeONORM) provides robustness against asymmetries in comparative transcriptome
      profiles and avoids false calls.
AB  - Studies on high-throughput global gene expression using microarray technology
      have generated ever larger amounts of systematic transcriptome data. A major
      challenge in exploiting these heterogeneous datasets is how to normalize the
      expression profiles by inter-assay methods. Different non-linear and linear
      normalization methods have been developed, which essentially rely on the
      hypothesis that the true or perceived logarithmic fold-change distributions
      between two different assays are symmetric in nature. However, asymmetric gene
      expression changes are frequently observed, leading to suboptimal normalization
      results and in consequence potentially to thousands of false calls. Therefore, we
      have specifically investigated asymmetric comparative transcriptome profiles and
      developed the normalization using weighted negative second order exponential
      error functions (NeONORM) for robust and global inter-assay normalization.
      NeONORM efficiently damps true gene regulatory events in order to minimize their
      misleading impact on the normalization process. We evaluated NeONORM's
      applicability using artificial and true experimental datasets, both of which
      demonstrated that NeONORM could be systematically applied to inter-assay and
      inter-condition comparisons.

PMID- 16970550
TI  - Improve survival prediction using principal components of gene expression data.
AB  - The purpose of many microarray studies is to find the association between gene
      expression and sample characteristics such as treatment type or sample phenotype.
      There has been a surge of efforts developing different methods for delineating
      the association. Aside from the high dimensionality of microarray data, one well
      recognized challenge is the fact that genes could be complicatedly inter-related,
      thus making many statistical methods inappropriate to use directly on the
      expression data. Multivariate methods such as principal component analysis (PCA)
      and clustering are often used as a part of the effort to capture the gene
      correlation, and the derived components or clusters are used to describe the
      association between gene expression and sample phenotype. We propose a method for
      patient population dichotomization using maximally selected test statistics in
      combination with the PCA method, which shows favorable results. The proposed
      method is compared with a currently well-recognized method.

PMID- 16970551
TI  - Predicting the subcellular localization of human proteins using machine learning
      and exploratory data analysis.
AB  - Identifying the subcellular localization of proteins is particularly helpful in
      the functional annotation of gene products. In this study, we use Machine
      Learning and Exploratory Data Analysis (EDA) techniques to examine and
      characterize amino acid sequences of human proteins localized in nine cellular
      compartments. A dataset of 3,749 protein sequences representing human proteins
      was extracted from the SWISS-PROT database. Feature vectors were created to
      capture specific amino acid sequence characteristics. Relative to a Support
      Vector Machine, a Multi-layer Perceptron, and a Naive Bayes classifier, the C4.5
      Decision Tree algorithm was the most consistent performer across all nine
      compartments in reliably predicting the subcellular localization of proteins
      based on their amino acid sequences (average Precision=0.88; average
      Sensitivity=0.86). Furthermore, EDA graphics characterized essential features of
      proteins in each compartment. As examples, proteins localized on the plasma
      membrane had higher proportions of hydrophobic amino acids; cytoplasmic proteins
      had higher proportions of neutral amino acids; and mitochondrial proteins had
      higher proportions of neutral amino acids and lower proportions of polar amino
      acids. These data showed that the C4.5 classifier and EDA tools can be effective
      for characterizing and predicting the subcellular localization of human proteins
      based on their amino acid sequences.

PMID- 16970552
TI  - PHProteomicDB: a module for two-dimensional gel electrophoresis database creation
      on personal web sites.
AB  - PHProteomicDB is a PHP-written module to help researchers in proteomics to share
      two-dimensional electrophoresis gel data using personal web sites. No technical
      or PHP knowledge is necessary except a few basics about web site management.
      PHProteomicDB has a user-friendly administration interface to enter and update
      data. It creates web pages on the fly displaying gel characteristics, gel
      pictures, and numbered gel spots with their related identifications pointing to
      their reference pages in protein databanks. The module is freely available at
      http://www.huvec.com/index.php3?rub=Download.

PMID- 16970553
TI  - Meta-analysis: anticholinergics, but not beta-agonists, reduce severe
      exacerbations and respiratory mortality in COPD.
AB  - BACKGROUND: Anticholinergics and beta2-agonists have generally been considered
      equivalent choices for bronchodilation in chronic obstructive pulmonary disease
      (COPD). OBJECTIVE: To assess the safety and efficacy of anticholinergics and
      beta2-agonists in COPD. DESIGN: We comprehensively searched electronic databases
      from 1966 to December 2005, clinical trial websites, and references from selected
      reviews. We included randomized controlled trials of at least 3 months duration
      that evaluated anticholinergic or beta2-agonist use compared with placebo or each
      other in patients with COPD. MEASUREMENTS: We evaluated the relative risk (RR) of
      exacerbations requiring withdrawal from the trial, severe exacerbations requiring
      hospitalization, and deaths attributed to a lower respiratory event. RESULTS:
      Pooled results from 22 trials with 15,276 participants found that anticholinergic
      use significantly reduced severe exacerbations (RR 0.67, confidence interval [CI]
      0.53 to 0.86) and respiratory deaths (RR 0.27, CI 0.09 to 0.81) compared with
      placebo. Beta2-agonist use did not affect severe exacerbations (RR 1.08, CI 0.61
      to 1.95) but resulted in a significantly increased rate of respiratory deaths (RR
      2.47, CI 1.12 to 5.45) compared with placebo. There was a 2-fold increased risk
      for severe exacerbations associated with beta2-agonists compared with
      anticholinergics (RR 1.95, CI 1.39 to 2.93). The addition of beta2-agonist to
      anticholinergic use did not improve any clinical outcomes. CONCLUSION: Inhaled
      anticholinergics significantly reduced severe exacerbations and respiratory
      deaths in patients with COPD, while beta2-agonists were associated with an
      increased risk for respiratory deaths. This suggests that anticholinergics should
      be the bronchodilator of choice in patients with COPD, and beta2-agonists may be
      associated with worsening of disease control.

PMID- 16970554
TI  - Simultaneous control of intermediate diabetes outcomes among Veterans Affairs
      primary care patients.
AB  - BACKGROUND: Guidelines recommend tight control of hemoglobin A1c (HbA1c), low
      density lipoprotein cholesterol (LDL-C), and blood pressure (BP) for patients
      with diabetes. The degree to which these intermediate outcomes are simultaneously
      controlled has not been extensively described. OBJECTIVE: Describe the degree of
      simultaneous control of HbA1c, LDL-C, and BP among Veterans Affairs (VA) diabetes
      patients defined by both VA and American Diabetes Association (ADA) guidelines.
      DESIGN: Cross-sectional cohort. PATIENTS: Eighty-thousand two hundred and seven
      VA diabetes patients receiving care between October 1999 and September 2000.
      MEASURMENTS: We defined simultaneous control of outcomes using 1997 VA Guidelines
      (in place in 2000) (HbA1c < 9.0%; LDL-C < 130 mg/dL; systolic BP < 140 mmHg; and
      diastolic BP < 90 mmHg) and 2004 ADA guidelines (HbA1c < 7.0%; LDL-C < 100 mg/dL;
      systolic BP < 130 mmHg; and diastolic BP < 80 mmHg). A patient is considered to
      have simultaneous control of the intermediate outcomes for a given definition if
      the average of measurements for each outcome was below the defined threshold
      during the study period. RESULTS: Using VA guidelines, 31% of patients had
      simultaneous control. Control levels of individual outcomes were: HbA1c (82%),
      LDL-C (77%), and BP (48%). Using ADA guidelines, 4% had simultaneous control.
      Control levels of individual outcomes were: HbA1c (36%), LDL-C (41%), and BP
      (23%). Associations between individual risk factors were weak. There was a modest
      association between LDL-C control and control of HbA1c (odds ratio [OR] 1.51; 95%
      confidence interval [CI] 1.44, 1.58). The association between LDL-C and BP
      control was clinically small (1.26; 1.21, 1.31), and there was an extremely small
      association between BP and HbA1c control (0.95; 0.92, 0.99). Logistic regression
      modeling indicates greater body mass index, African American or Hispanic race
      ethnicity, and female gender were negatively associated with simultaneous
      control. CONCLUSION: While the proportion of patients who achieved minimal levels
      of control of HbA1c and LDL-C was high, these data indicate a low level of
      simultaneous control of HbA1c, LDL-C, and BP among patients with diabetes.

PMID- 16970555
TI  - Four physician communication styles in routine Japanese outpatient medical
      encounters.
AB  - BACKGROUND: Few studies have explored how physicians approach medical encounters
      in Japan. OBJECTIVE: This study examined how Japanese physicians conduct routine
      medical encounters in the context of outpatient care to patients with
      nonmalignant disorders. DESIGN: Qualitative study using semi-structured
      interviews and direct observation. SETTING: The outpatient department of a
      general hospital located in an urban area of Japan. PARTICIPANTS: Physicians and
      nurses providing care and patients receiving care for nonmalignant disorders.
      RESULTS: A 2-dimensional model was developed, with patient communication (how
      physician interacted with patients) along 1 axis, and nurse communication (how
      physicians collaborated with nursing staff) along the other axis. Four physician
      communication styles (individually adaptive, individually defined,
      collaboratively adaptive, and collaboratively defined) were identified as typical
      ways in which the Japanese physicians in the sample interacted with patients and
      nurses during routine medical encounters. CONCLUSIONS: Results suggest the need
      for a multiprovider-patient model of medical communication among physician,
      nurse, and patient. Further research is needed to establish the applicability of
      this model to the communication styles of physicians in other countries.

PMID- 16970556
TI  - Potential outcome factors in subacute combined degeneration: review of
      observational studies.
AB  - BACKGROUND: Subacute combined degeneration is an acquired myelopathy caused by
      vitamin B12 deficiency. Therapy with B12 leads to improvement in most but to
      complete recovery in only a few patients. Prognostic indicators in subacute
      combined degeneration are unknown; therefore, predicting complete recovery of
      neurologic deficits is challenging. PURPOSE: To identify potential correlates of
      outcome and to generate hypotheses concerning predictors of complete resolution
      of neurologic deficits in subacute combined degeneration. DATA SOURCE: We
      searched EMBASE (1974 to October 2005), MEDLINE (1968 to October 2005), and
      references from identified reports. REPORTS SELECTION: Reports of patients with
      subacute combined degeneration containing results of magnetic resonance imaging
      (MRI) and description of outcome and 1 patient treated by the authors. DATA
      EXTRACTION, SYNTHESIS: We extracted data from 45 reports and 57 patients (36
      males, 21 females; age range: 10 to 81) with a diagnosis of subacute combined
      degeneration, and estimated the strength of association between clinical,
      laboratory, and radiological factors and complete resolution of signs and
      symptoms. RESULTS: Eight patients (14%) achieved clinical resolution and 49 (86%)
      improved with B12 therapy. The absence of sensory dermatomal deficit, Romberg,
      and Babinski signs were associated with a higher complete resolution rate.
      Patients with MRI lesions in < or = 7 segments and age less than 50 also appear
      to have higher rates of complete resolution. CONCLUSIONS: B12 therapy is reported
      to stop progression and improve neurologic deficits in most patients with
      subacute combined degeneration. However, complete resolution only occurs in a
      small percentage of patients and appears to be associated with factors suggestive
      of less severe disease at the time of diagnosis.

PMID- 16970557
TI  - Weight-related perceptions among patients and physicians: how well do physicians
      judge patients' motivation to lose weight?
AB  - BACKGROUND: Prior studies suggest that patients and physicians have different
      perceptions and expectations surrounding weight; however, few studies have
      directly compared patients' and physicians' perspectives. OBJECTIVES: (1) To
      measure the extent to which obese patients and their physicians have discrepant
      weight-related perceptions, and (2) to explore patient and physician
      characteristics that may influence patient-physician discrepancy in motivation to
      lose weight. DESIGN AND PARTICIPANTS: Four hundred and fifty-six obese patients
      (302 females; mean age = 55.1 years; mean BMI = 37.9) and their 28 primary care
      physicians (22 males, mean age = 44.1 years) from nonmetropolitan practices
      completed an anonymous survey after an office visit. MEASURES: Weight-related
      perceptions included perceived weight status, health impact of weight, 1-year
      weight loss expectations, and motivation to lose weight. Correlates included
      patient and physician sex, age, and BMI; physicians' reported frequency,
      perceived patient preference, and confidence for weight counseling; and practice
      characteristics (e.g., years in practice). RESULTS: Physicians assigned patients
      to heavier descriptive weight categories and reported a worse health impact than
      patients perceived for themselves, whereas patients believed they could lose more
      weight and reported a higher motivation to lose weight than their physicians
      perceived for patients (P < .001). Physicians who believed patients preferred to
      discuss weight more often (P = .001) and who saw more patients per week (P = .04)
      were less likely to underestimate patient motivation. CONCLUSIONS: Patients
      reported more optimistic weight-related perceptions and expectations than their
      physicians. Further research is needed to determine how these patient-physician
      discrepancies may influence weight loss counseling in primary care.

PMID- 16970558
TI  - Middle-aged and mobility-limited: prevalence of disability and symptom
      attributions in a national survey.
AB  - BACKGROUND: Lower limb mobility disabilities are well understood in older people,
      but the causes in middle age have attracted little attention. OBJECTIVES: To
      estimate the prevalence of mobility disabilities among noninstitutionalized
      adults in England and to compare the disabling symptoms reported by middle-aged
      and older people. DESIGN: Cross-sectional data from the 2002 English Longitudinal
      Study of Ageing (ELSA). Mobility disability was identified by level of reported
      difficulty walking a quarter mile. PARTICIPANTS: Eleven thousand two hundred
      sixteen respondents aged 50 years and older living in private households in 2002.
      RESULTS: The prevalence of difficulty walking a quarter mile increases sharply
      with age, but even in the middle-aged (50 to 64 years age-group) 18% (95%
      confidence interval [CI]: 16% to 19%) of men and 19% (95% CI: 17% to 20%) of
      women reported some degree of difficulty. Of the 16 main symptoms reported as
      causing mobility disability in middle age, 2 dominated: pain in the leg or the
      foot (43%; 95% CI: 40% to 46%) and shortness of breath/dyspnea (21%; 95% CI: 18%
      to 23%). Fatigue or tiredness, and stability problems were cited by only 5% and
      6%, respectively. These proportions were slightly different from those in the 65
      to 79-year age group: 40%, 23%, 6%, and 8%, respectively. CONCLUSIONS: Mobility
      (walking) disabilities in the middle-aged are relatively common. The symptoms
      reported as causes in this age group differ little from those reported by older
      groups, and are dominated by lower limb pain and shortness of breath. More
      clinical attention paid to disabling symptoms may lead to disability reductions
      in later life.

PMID- 16970559
TI  - The influence of type and severity of mental illness on receipt of screening
      mammography.
AB  - BACKGROUND: Women with mental illness may be at risk for failure to receive
      recommended preventive services such as mammography. Little is known about
      whether the type or severity of mental illness influences receipt of preventive
      services. OBJECTIVE: To measure the influence of type and severity of mental
      illness on receipt of mammography. DESIGN: Retrospective study of administrative
      claims data, 1996 to 2001. SUBJECTS: Privately insured women age 40 to 64 years,
      with and without claims for mental illness, and who were eligible for mammography
      between 1996 and 2001. MEASUREMENT: Odds ratios (OR) for receipt of screening
      mammography, any mammography, and follow-up mammography, adjusted for age, rural
      location, utilization of nonmental health services, and severity and type of the
      mental disorder. Severity measures were based on utilization of outpatient and
      inpatient mental health services and presence of comorbid substance use disorder.
      RESULTS: Women with any mental disorder were significantly less likely to receive
      mammography than controls. This was strongly influenced by severity of mental
      illness (any mammography: moderate severity OR 0.62; confidence interval [CI]
      0.59 to 0.66: high severity OR 0.38; CI 0.33 to 0.43). Whereas severity
      contributed to lower receipt of mammography among women with mood and anxiety
      disorders, women with psychotic, alcohol, and substance abuse disorders had
      decreased odds for receipt of mammography regardless of severity. CONCLUSIONS:
      Women with mental disorders are at risk for failure to receive mammography, a
      recommended preventive service. Women with severe mental illness or psychotic and
      substance abuse disorders should be targeted to ensure delivery of mammography.

PMID- 16970560
TI  - Brief report: lack of a race effect in primary care ratings among women veterans.
AB  - OBJECTIVE: To explore the effect of race on primary care quality and satisfaction
      among women in the Department of Veterans Affairs (VA). METHODS: We used a mail
      survey to measure primary care quality and satisfaction. We focused on 4 primary
      care domains: patient preference for provider, interpersonal communication,
      accumulated knowledge, and coordination. We performed univariate analyses to
      compare variables by race and multiple logistic regression analysis to examine
      the effect of race on the probability of reporting a perfect score on each
      domain, while adjusting for patient characteristics and site. RESULTS: Black
      women were younger, unmarried, educated, of higher income, and reported female
      providers and gynecological care in VA more often. In regression analysis, race
      was not significantly associated with any primary care domain or satisfaction.
      Gynecological care from VA provider was associated with perfect ratings on
      patient preference for provider (odds ratio [OR] 2.0, 95% confidence intervals
      [CI] 1.3, 3.1), and satisfaction (OR 1.6, 95% CI 1.2, 2.3), while female provider
      was associated with interpersonal communication (OR 1.9, 95% CI 1.4, 2.6).
      CONCLUSIONS: While demographics and health experiences vary by race among
      veterans, race had no effect on primary care ratings. Future studies need to
      determine whether this racial equity persists in health outcomes among women
      veterans.

PMID- 16970561
TI  - Teaching medical students about communicating with patients with major mental
      illness.
AB  - Persons with major mental illness often have chronic diseases and poor physical
      health. Therefore, all practicing physicians should learn about communicating
      effectively with these patients. Few efforts to teach medical students
      communication skills have specifically targeted patients with major mental
      illness. Indeed, most of the limited literature on this topic is decades old,
      predating significant scientific advances in cognitive neuroscience and
      psychiatric therapeutics and changes in social policies regarding major mental
      illness. To gather preliminary insight into training needs, we interviewed 13
      final-year students from 2 Boston medical schools. Students' observations
      coalesced around 4 themes: fears and anxieties about interacting with persons
      with major mental illness; residents "protecting" students from patients with
      major mental illness; lack of clinical maturity; and barriers to learning during
      psychiatry rotations. Educational researchers must explore ways to better prepare
      young physicians to communicate effectively with patients with major mental
      illness.

PMID- 16970562
TI  - Time to question long-term safety of routine scheduled inhaled beta-2-agonist
      treatment for COPD.

PMID- 16970563
TI  - Depression in primary care: encouragement and caution for the business case.

PMID- 16970564
TI  - Letter to the editor regarding Sullivan et al.

PMID- 16970565
TI  - Context matters, but let's not go too far.

PMID- 16970569
TI  - Transfer of the antidepressant mirtazapine into breast milk.
AB  - AIMS: To investigate the transfer of mirtazapine and desmethylmirtazapine into
      milk and to calculate dose to the infant via milk. METHODS: Plasma and milk
      samples were obtained from eight breast-feeding women who were taking a median
      dose of 38 mg mirtazapine per day. Milk/plasma ratio (M/P) and infant doses were
      estimated by standard methods. The infants were examined clinically and in four
      infants blood was taken for analysis. RESULTS: Mean (95% confidence interval)
      relative infant doses for mirtazapine and desmethylmirtazapine (n = 8) were 1.5%
      (0.8, 2.2) and 0.4% (0.2, 0.6) respectively. The mean M/P (area under curve n =
      4, single or paired samples n = 3) was 1.1 (0.7,1.5) for mirtazapine and 0.6
      (0.5, 0.7) for desmethylmirtazapine. No adverse effects were seen. Mirtazapine
      was detected (1.5 microg l(-1)) in only one of four infants tested. CONCLUSION:
      We suggest that mirtazapine use by lactating women is safe for the breast-fed
      infant. Nevertheless, each decision to breast feed should always be made on the
      basis of an individual risk/benefit analysis.

PMID- 16970570
TI  - Towards a more prescriptive follow-up regimen for colorectal cancer.

PMID- 16970571
TI  - Laparoscopic surgery for ulcerative colitis - a meta-analysis.
AB  - OBJECTIVE: To assess the safety and feasibility of laparoscopic surgery for
      patients with ulcerative colitis. METHODS: A search of published studies in
      English between January 1992 and September 2005 was obtained, using the MEDLINE
      and PubMed databases and the Cochrane Central Register of Controlled Trials. Two
      independent assessors reviewed the studies using a standardized protocol. Where
      raw data, means and standard deviations were available, meta-analysis was
      performed using the Forest plot review. Studies where medians and ranges were
      presented were separately analysed. RESULTS: The duration of surgery for
      laparoscopic and open procedures were similar (weighted mean difference 62.92
      min, P = 0.19). Patients were able to tolerate oral intake significantly earlier,
      with a weighted mean difference of 1.39 days (P = 0.002), but recovery of bowel
      function was similar (weighted mean difference 0.73 days, P = 0.36). The length
      of hospital stay was shorter for patients who had undergone laparoscopic surgery,
      with a weighted mean difference of 2.64 days (P = 0.003). The complication rate
      was higher in open colectomy, compared to laparoscopic colectomy (67.6%vs 39.7%,
      P = 0.005). For restorative proctocolectomy, complication rates were comparable
      between the laparoscopic and open groups (P = 0.25). CONCLUSIONS: The time taken
      to perform laparoscopic surgery is similar to open surgery. Patients are able to
      tolerate oral intake earlier, and have a shorter hospitalization. Laparoscopic
      colectomy was safer compared to the open procedure, but both were equally safe
      for patients who had restorative proctocolectomy. Thus, laparoscopic surgery for
      ulcerative colitis is both safe and feasible.

PMID- 16970572
TI  - Gastrointestinal manifestations of chronic granulomatous disease.
AB  - OBJECTIVE: Chronic granulomatous disease is a rare clinical entity characterized
      by recurrent infective and inflammatory complications. Patients are usually
      assigned to specialist centres, but nonspecialist clinicians may be required to
      treat these patients in the emergency setting. This review serves as a management
      guide to those clinicians who are faced with patients presenting with
      gastrointestinal manifestations of chronic granulomatous disease. METHODS: This
      review is based on a literature search (Medline and NLM PubMed) with manual cross
      referencing of all articles related to gastrointestinal chronic granulomatous
      disease. RESULTS: Gastrointestinal tract involvement is present in most affected
      patients. Clinical presentation can mimic common surgical complications such as
      colitis, perianal sepsis, gastric outlet obstruction and liver abscess. A history
      of recurrent infections during childhood is common. Management involves
      haematological, microbiological, endoscopic and radiological investigations.
      Treatment modalities include early aggressive empirical antimicrobial therapy for
      sepsis, immunomodulation for inflammatory complications and surgical drainage of
      abscesses. CONCLUSION: Early involvement of a centre with immunological expertise
      combined with aggressive management of complications significantly improves
      morbidity and mortality from this rare condition.

PMID- 16970573
TI  - Curative resection for low rectal adenocarcinoma: abdomino-perineal vs anterior
      resection.
AB  - OBJECTIVE: Local recurrence after abdomino-perineal excision of the rectum for
      tumours has been reported to occur in up to a third of patients in contrast to 4%
      after restorative anterior resection. METHOD: Low rectal tumours were defined as
      tumours within 8 cm of the anal verge and were treated by either stapled low
      anterior resection (SLAR) or abdomino-perineal excision of the rectum (APER). One
      hundred and seventy-eight patients with tumours in the lower third of the rectum
      (30% of 591 rectal cancers) underwent surgical resection between 1980 and 2001.
      Data were collected prospectively; 68 (38%) had SLAR and 110 (62%) had APER with
      median follow up of approximately 12 years; 54 SLAR (79%) and 76 APER (69%) had
      curative procedures on clinical and pathological criteria. RESULTS: Local and
      distant recurrence occurred in seven (13%) and eight (15%) patients in the SLAR
      group and six (8%) and 14 (18%) patients in the APER group, respectively. Overall
      5-year survival was 63% and 60% in the SLAR and APER groups, respectively
      CONCLUSION: For rectal cancers within 8 cm of the anal verge, both procedures
      achieved equivalent results measured by low local recurrence rates and overall
      survival.

PMID- 16970574
TI  - Low anterior resection with total mesorectal excision for rectal cancer:
      functional assessment and factors affecting outcome.
AB  - OBJECTIVE: Many patients experience disordered defaecation after low anterior
      resection of the rectum (LARR). We analysed the anorectal function of these
      patients to determine which factors might contribute to this problem. PATIENTS
      AND METHODS: Between November 2002 and January 2004, 18 consecutive patients (11
      males and 7 females) who underwent LARR with total mesorectal excision (TME) for
      rectal cancer were assessed by anorectal manometry, balloon proctometry and the
      Wexner continence questionnaire before operation and at 6 months and 1 year
      following stoma closure. Sixteen volunteers (11 males and 5 females) were
      evaluated for comparison. Stepwise logistic regression was performed for
      variables that were highly significant at univariate analysis. RESULTS: The mean
      daily preoperative stool frequency was 2, mean basal pressure (MBP) 43.12 cm
      H(2)O, maximum threshold volume (MTV) 181.8 ml, length of high-pressure zone
      (HPZ) 3.11 cm and the rectoanal inhibitory reflex (RAIR) was present in all the
      patients. Twelve months after stoma closure, the stool frequency was 3.3, MBP
      37.7 cm H(2)O, MTV 146.3 ml, length of HPZ 2.88 cm and Wexner score 4.37.
      Comparing patients having a good anorectal function (Wexner score > or = 5) with
      those having an unsatisfactory function, we found that, on multivariate analysis,
      the factors that independently contributed to a poor outcome at 12 months after
      operation were the absence of RAIR as well as an MTV and HPZ below the fifth
      percentile of normal individuals. CONCLUSIONS: Many patients undergoing LARR with
      TME for rectal cancer experience an anterior resection syndrome that persists for
      at least 1 year. Those with no RAIR and subnormal MTV and HPZ lengths can be
      predicted to have an unsatisfactory outcome.

PMID- 16970575
TI  - Safety of bowel resection for colorectal surgical emergency in the elderly.
AB  - OBJECTIVE: Colorectal emergency requiring radical surgery is becoming
      increasingly frequent in the elderly and problems remain as regards the best
      management policy. Our long-time experience is presented in this study. PATIENTS
      AND METHODS: In the last 23 years, 105 elderly patients, aged > or = 65 years,
      with colorectal disease underwent an emergency operation in our Surgical
      Department. Forty-five patients (mean age 72 years) had benign disease and 60
      patients (mean age 76.5 years) colorectal carcinoma. RESULTS: The carcinoma was
      located in the left colon (68%), right colon (18%) and rectum (14%). Mostly,
      patients with malignant cancer presented with obstructive ileus, and patients
      with benign tumours with perforation and peritonitis, with a predominance of
      diverticulitis. A resection operation either with primary anastomosis or
      Hartmann's procedure was performed in 75% of cases; in the rest, only palliation
      was resorted to. Forty-three percent of the patients with colorectal cancer
      emergency were > or = 80 years of age. The mean morbidity was 25% and mortality
      17%, which make up to 33% and 26.6% for benign disease, and 20% and 10% for
      malignant cancer, respectively. The mortality rate was higher in patients with
      perforation than those with obstruction. CONCLUSION: Advanced age is not a
      contraindication to radical surgery in case of colorectal emergency in the
      elderly. In the majority, a resection operation is feasible. In high-risk
      patients, colostomy is a life-saving alternative.

PMID- 16970576
TI  - Long-term, health-related, quality of life comparison in patients undergoing
      single stage vs staged resection for complicated diverticular disease.
AB  - OBJECTIVE: To evaluate long-term health-related quality of life, for single
      staged and staged resections following reversal, for complicated diverticular
      disease. PATIENTS AND METHODS: Between 1981 and 2003, 188 patients undergoing
      single stage (n = 158) or staged resection (n = 30) completed the SF-36
      questionnaire. Health-related quality of life (HRQL) was compared between the two
      groups and the US normal population based on the eight domains of the SF-36. HRQL
      analysis was also performed at various time intervals. The effect of age and
      postoperative complications on HRQL was also determined. Functional and
      postoperative outcomes were also assessed. RESULTS: The single and staged
      resection groups differed in the presence of comorbidity, degree of peritoneal
      contamination and operative urgency. No difference in functional outcomes or HRQL
      was found, even after analysing time-interval subgroups. Social functioning and
      general health was substantially worse in both groups when compared to US norms.
      Ageing was found to significantly reduce physical functioning (P < 0.001) and
      physical and emotional role limitations (P < 0.001 for both). Post-operative
      complications significantly reduced scores when compared to patients without
      complications, for physical functioning (63.57 vs 78.7, respectively; P < 0.001),
      physical role limitation (80.65 vs 86.9, respectively; P < 0.001) and bodily pain
      (66.67 vs 74.81, respectively; P < 0.01). CONCLUSIONS: No significant difference
      in long-term HRQL was found in patients undergoing single staged or staged
      resection for complicated diverticular disease. There was significant impact of
      ageing and postoperative complications on physical health. Prospective studies
      that include pre-operative data on HRQL are required to compare the two operative
      techniques, with emphasis on quality of life of patients left with a permanent
      stoma.

PMID- 16970577
TI  - Prevention of parastomal hernia using preperitoneal mesh: a prospective
      observational study.
AB  - OBJECTIVE: Parastomal hernia is a common complication after stoma formation. The
      objective of the study was to see whether placing prophylactic preperitoneal mesh
      could reduce the incidence of parastomal hernia. METHOD: Patients having elective
      bowel surgery requiring permanent stoma were included in this study. The time
      required for mesh insertion, day of stoma function, and early complications were
      recorded. Follow up was at 6 weeks, 3-monthly for the first year and at 6-monthly
      intervals thereafter. RESULTS: Eighteen patients fulfilled the inclusion criteria
      and were followed up for 6-28 months (mean 16.05). The time taken for mesh
      placement was 12-22 min (mean 14). One patient had to have revision surgery on
      day 1 for stomal necrosis - the mesh was left in situ in that instance. This
      patient developed superficial laparotomy wound infection. During the follow up,
      no patients developed parastomal hernia, stomal prolapse, stenosis, retraction,
      fistula or obstruction. CONCLUSION: The early results, in this group of patients,
      show that prophylactic polypropylene mesh insertion at the time of permanent
      stoma formation is encouraging and long-term results are awaited.

PMID- 16970578
TI  - Consumer impact of an interactive decision aid for rectal cancer patients offered
      adjuvant therapy.
AB  - OBJECTIVE: There is increasing interest in the use of decision aids (DAs) to
      facilitate patient involvement in clinical decisions. This study explored the
      views of patients with colorectal cancer and participants in a community bowel
      screening service regarding an interactive DA concerning adjuvant treatment for
      rectal cancer, and the impact of the aid on knowledge, anxiety, attitudes and
      preferences for treatment options. METHOD: Fourteen patients with colorectal
      cancer participated in four focus groups. Eighty-nine participants in a community
      bowel screening service completed a questionnaire before and 1 week after viewing
      the DA. Thirty were randomly selected to participate in a telephone interview to
      obtain qualitative feedback about the DA. RESULTS: Focus group participants
      reported using information to evaluate their doctor's care and expertise, or to
      prepare themselves for future symptoms and side-effects. Most supported the use
      of a DA and preferred pie charts to convey risk information. Within the community
      sample, anxiety remained stable and knowledge increased after exposure to the DA.
      Almost all participants found the DA useful and easy to understand, and felt it
      would make the process of decision making easier. CONCLUSION: A DA regarding
      adjuvant therapy for rectal cancer appears to be valued and to produce positive
      outcomes. A randomized controlled trial of this intervention is now required.

PMID- 16970579
TI  - Convalescence after colonic surgery with fast-track vs conventional care.
AB  - OBJECTIVE: To compare convalescence after colonic surgery with a fast-track
      rehabilitation programme vs conventional care. BACKGROUND: Introduction of a
      multimodal rehabilitation programme (fast-track) with focus on epidural
      anaesthesia, minimal invasive surgical techniques, optimal pain control, and
      early nutrition and mobilization together with detailed patient information have
      led to a shorter hospital stay after colonic surgery. There are not much data on
      convalescence after discharge. METHODS: A prospective, controlled, non-randomized
      interview-based assessment in 160 patients undergoing an elective, uncomplicated,
      open colonic resection or the Hartmann reversal procedure with a fast-track or a
      conventional care programme in two university hospitals. A structured interview
      based assessment was performed preoperatively, and day 14 and 30 postoperatively.
      RESULTS: Patients undergoing colonic surgery with a fast-track programme regained
      functional capabilities earlier with less fatigue and need for sleep compared
      with patients having conventional care. Despite early discharge of the fast-track
      patients (mean 3.4 days vs 7.5 days), no differences were found according to the
      need for home care, social care and visit to general practitioners, although the
      fast-track group had an increased number of visits at the outpatient clinic for
      wound care. More patients in the fast-track group were re-admitted, but the
      overall mean total hospital stay was 4.2 days vs 8.3 days in the conventional
      group. CONCLUSION: A fast-track rehabillitation programme led to a shorter
      hospital stay, less fatigue and earlier resumption of normal activities, without
      the increased need for support after discharge compared with conventionally
      treated patients after uncomplicated colonic resection.

PMID- 16970580
TI  - Reported symptoms, diagnostic delay and stage of colorectal cancer: a population
      based study in Denmark.
AB  - OBJECTIVE: The primary prognostic factor for colorectal cancer (CRC) is stage.
      Any association between symptoms, diagnostic delay and stage may have
      implications for the clinical course of the disease. We examined the association
      between symptoms and diagnostic delay and between symptoms and stage, and
      assessed whether the associations differed for colon cancer (CC) and rectal
      cancer (RC). PATIENTS AND METHODS: Population-based prospective observational
      study based on 733 Danish CRC patients. Diagnostic delay and patients' reported
      symptoms were determined through questionnaire-interviews. Dukes' stage was
      obtained from medical records and pathology forms. Diagnostic delay was
      categorized into three delay groups: < or = 60, 61-150 and > 150 days. Stage was
      classified into nonadvanced (Dukes' A and B) or advanced (Dukes' C and D)
      cancers. We calculated the frequency of the most frequently reported initial
      symptom or symptom complex for CC and RC patients, and evaluated the frequency of
      patients with different initial symptoms/symptom complexes in the three delay
      groups. For the most frequent initial symptoms/symptom complexes, we calculated
      the frequencies according to stage, and estimated the relative risk of having an
      advanced stage, with 95% confidence intervals. RESULTS: The most frequent initial
      symptoms/symptom complexes were very vague symptoms for CC and rectal bleeding
      for RC. For both CC and RC, rectal bleeding was significantly associated with
      nonadvanced stage. The relative risk of having an advanced cancer was 0.6 for
      monosymptomatic rectal bleeding and 0.7 for rectal bleeding combined with other
      symptoms. CONCLUSIONS: Initial symptoms of CC were often very vague, making it
      difficult to identify a precise start date. The most frequent initial
      symptom/symptom complex for RC - rectal bleeding - was better defined. Rectal
      bleeding was significantly associated with nonadvanced CC and RC and a
      significantly decreased relative risk of having an advanced cancer.

PMID- 16970581
TI  - The prognostic impact of the time interval to recurrence for the mortality in
      recurrent colorectal cancer.
AB  - OBJECTIVE: The risk of a cancer recurrence has been correlated with the stage of
      the primary tumour at the time of presentation. However, once a recurrence has
      developed, the primary tumour stage may not be the determining prognostic factor
      anymore. The objective of this study was (i) to evaluate the association between
      the recurrence interval and the outcome of the recurrence, and (ii) to determine
      whether that interval was affected by the use of adjuvant radiation and/or
      chemotherapy. METHOD: This retrospective study analysed 212 patients who
      developed recurrent colorectal cancer from 1987 to 1993. Primary parameters such
      as age, gender, primary tumour site and stage, and use of postoperative adjuvant
      treatment were correlated with the recurrence interval, the type and site of the
      recurrence (i.e. locoregional vs distant metastases), and the outcome. Uni- and
      multivariate analysis was used to compare the recurrence interval and survival
      between different subgroups as defined by risk factors. RESULTS: The mean time
      between the primary and the recurrent tumour was 25 months (range 1-252 months)
      with 82% of the recurrences developing within 3 years after surgery. The
      recurrence interval was inversely correlated with the initial tumour stage. Poor
      survival was associated with a short recurrence interval (less than 12 months)
      and a distant recurrence site. Even after adjusting for the initial tumour stage,
      the use of adjuvant treatment did not prolong the interval, i.e. delay the onset
      of recurrent cancer. CONCLUSION: The recurrence interval of colorectal cancer is
      a prognostic factor. However, the use of adjuvant therapy did not prolong that
      interval.

PMID- 16970582
TI  - Surgical treatment of complicated pilonidal disease: limited separate elliptical
      excision with primary closure.
AB  - OBJECTIVE: We aimed at treating complicated pilonidal sinus (PS) patients by a
      simple and effective surgical procedure. METHOD: Between 2000 and 2004, 24
      selected complicated PS patients were treated with 'limited separate elliptical
      excision and primary closure'. Patients with extensive or bilateral gluteal
      involvement, having more lateral, caudal or cephalic sinuses, multiple
      recurrences and unhealed chronic wounds after pilonidal surgery were included.
      Asymmetric excision and primary closure was performed to main diseased tissue in
      the midline. Additionally, small separate elliptical excisions with primary
      closure were performed in other involved tissues. The fistula tract or
      granulation tissue were excised subcutaneously if present. All patients were
      operated under local anaesthesia. The fascial attachments between the skin and
      coccyx were released at the deep point in the midline and at one side of wound.
      Suction drains and prophylactic antibiotics were used; subcutaneous tissues were
      closed with running polyglactin sutures and skin with polypropylene
      subcutaneously. RESULTS: The mean age of patients was 28.4 years (range 18-38).
      The mean follow-up time was 2.8 years. One recurrence, one seroma, one wound
      infection and one wound breakdown were recorded. Healing was always by first
      intention except in patients with wound infection and breakdown. CONCLUSION: Most
      of the complicated PS patients can be operated with acceptable rates of
      recurrences and complications by using 'limited separate elliptical excisions
      with primary closure'.

PMID- 16970583
TI  - Transanal endoscopic microsurgery: a necessary requirement?
AB  - INTRODUCTION: There has been a gradual introduction of transanal endoscopic
      microsurgery (TEM) into UK practice although the uptake remains variable. This
      study aimed to assess the availability, application and referral pattern of TEM
      amongst colorectal surgeons. METHODS: A questionnaire was sent to all consultant
      members of the Association of Coloproctology. This considered their practice, the
      availability, application and referral pattern for TEM, and their views on
      application regarding a selection of rectal tumour scenarios. RESULTS: There were
      142 replies representing 116 hospitals and 297 colorectal surgeons. The median
      catchment area was 280,000 (range 70,000-1,000,000). TEM was available in 18% of
      hospitals and 72% either performed or referred patents for TEM. Of 21 units
      performing TEM, 15 received referrals. From 305 TEM procedures performed over the
      previous year, 206 were referred cases. Eighty-five per cent of consultants
      considered TEM a necessary technique for optimum management of rectal lesions.
      Although 61% of consultants considered endoanal excision optimal for low benign
      rectal tumours, 58% said TEM was optimal for midrectal lesions and between 30%
      and 55% for high rectal lesions depending if the tumour position was anterior or
      posterior, respectively. One-third of consultants would perform TEM for a low T1
      rectal carcinoma although half would proceed to anterior resection. DISCUSSION:
      TEM is considered to have a significant role in the optimal management of rectal
      lesions. The presence of the technique in a limited number of hospitals does
      appear to provide adequate resources although audit should continue to be
      centralized.

PMID- 16970584
TI  - Use of W-plasty in stenotic stoma: a new solution for an old problem.
AB  - INDICATION: Amongst late complications of stomas, stenosis can be difficult to
      treat. Repeated dilatations rarely achieve long-term resolution and re-fashioning
      is not always successful. Application of an existing plastic surgical technique
      to treat stomal stenosis is described. METHOD: After marking the skin, a W-plasty
      is made with a number of consecutive small triangular flaps through the skin. The
      corresponding mucosal margin is then made to interdigitate with this
      configuration and fixed using a Gillies corner stich with 5/0 Vycril rapide on a
      compound curved needle. RESULTS: Five patients underwent W-plasty reconstruction
      for a stenotic stoma. Median follow up was 12.5 months (range 11-15). No patient
      had stenosis of the stoma on review and the patient satisfaction rate was high.
      CONCLUSION: The W-plasty technique is a new treatment for stenotic stoma.

PMID- 16970585
TI  - Anal ulceration associated with Nicorandil: case series and review of the
      literature.
AB  - BACKGROUND: Use of Nicorandil in the treatment of ischaemic heart disease has
      been associated with oral, ileal and more recently anal ulceration. We report a
      series of six cases of peri-anal ulceration in patients on nicorandil therapy,
      their response to withdrawal of the drug and review the literature. METHODOLOGY:
      Systematic case note review of all patients with anal ulceration presenting to a
      single colorectal unit. Including detailed medical and drug history,
      morphological and histological appearances of the peri-anal ulcer after biopsy.
      Nicorandil therapy stopped in conjunction with physician and the progress of the
      ulcer monitored. Photographs taken before and after cessation of Nicorandil after
      informed consent. A literature search on Nicorandil combined with the key words:
      anal, peri-anal, ulceration and adverse drug effects was performed using the
      Cochrane Library Medline (January 1966 to June 2005) and Embase (January 1974 to
      June, 2005). RESULTS: Six patients were identified from our hospital records.
      Histological examination of all ulcers revealed nonspecific chronic inflammation.
      Five patients demonstrated healing of ulceration within six weeks of withdrawal
      of Nicorandil, the remaining patient had circumferential involvement of the anal
      canal and has not improved at 3-month review. One patient was recommenced on
      Nicorandil after healing due to refractory angina and ulceration recurred.
      CONCLUSIONS: We believe ulceration due to Nicorandil remains widely under
      diagnosed and the mechanism of ulceration is unclear. Despite diversion colostomy
      one of our patients continued with peri-anal ulceration, which may suggest a
      systemic mechanism rather than local irritation. Biopsy of these lesions is
      essential to exclude neoplastic process and inflammatory bowel disease.

PMID- 16970594
TI  - Ileostomy carcinomas: a review: the latent risk after colectomy for ulcerative
      colitis and familial adenomatous polyposis.

PMID- 16970595
TI  - Longitudinal evaluation of a fibrosis index combining MMP-1 and PIIINP compared
      with MMP-9, TIMP-1 and hyaluronic acid in patients with chronic hepatitis C
      treated by interferon-alpha and ribavirin.
AB  - We have recently described a fibrosis index combining serum procollagen type III
      N-terminal peptide (PIIINP) and matrix metalloproteinase 1 (MMP-1) concentrations
      for evaluating the amount of liver fibrosis in chronic hepatitis C patients. The
      aims of the present study were to validate this score in another cohort of
      patients and to assess its variations along those of TIMP-1, hyaluronic acid (HA)
      and MMP-9 during antiviral treatment. Seventy-nine patients treated by interferon
      alpha and ribavirin for 24 or 48 weeks were included. A liver biopsy was
      performed within the 6 months before the start of treatment. Serum markers were
      measured in serum collected the day of the liver biopsy, at start of treatment,
      and every 3 months during treatment and a 6-month follow-up period. The
      PIIINP/MMP-1 index was significantly correlated to the METAVIR fibrosis (r =
      0.68, P < 0.001). Its overall diagnostic value defined by the area under the
      receiver operating characteristics curves was 0.77 for discriminating F1 vs
      F2F3F4, and 0.81 for discriminating F1F2 vs F3F4, and was better than that
      observed for HA and TIMP-1. At the end of follow-up, the PIIINP/MMP-1 index
      significantly decreased in responders and remained stable in nonresponder
      patients. This decrease occurred early and continued regularly during the
      treatment period. This variation was because of both a decrease of PIIINP and an
      increase of MMP-1 concentrations. HA and TIMP-1 serum concentrations were also
      significantly lower at the end of follow-up in responder patients, but early
      changes were minimal and not influenced by the response to treatment. Our study
      shows that a noninvasive index combining PIIINP and MMP-1 is a useful tool to
      follow-up fibrosis change during and after antiviral therapy chronic hepatitis C
      patients.

PMID- 16970596
TI  - Diagnostic accuracy of a fibrosis serum panel (FIBROSpect II) compared with
      Knodell and Ishak liver biopsy scores in chronic hepatitis C patients.
AB  - Liver biopsy is the primary method of assessing liver injury in hepatitis C
      patients. FIBROSpect II (FS), a diagnostic panel of three extracellular matrix
      remodelling markers, may be useful as a noninvasive alternative to this
      procedure. The purpose of this study was to correlate FS results with liver
      fibrosis scores to determine if this test is sufficiently accurate to be a viable
      alternative to liver biopsy. A total of 142 serum specimens were evaluated for
      fibrosis with FS and were compared with Knodell and Ishak fibrosis scores. FS
      reports an index score ranging from 0.1 to 1.0, which corresponds to the
      probability of progressive liver fibrosis. Using a FS index cut-off of 0.42, 50
      of 54 patients with Ishak 3-6 were classified as having advanced fibrosis
      (METAVIR F2-F4) and 58 of 88 patients with Ishak 0-2 as having no/mild fibrosis
      (METAVIR F0-F1), resulting in a sensitivity of 93%, specificity of 66%, and an
      overall test accuracy of 76%. With a 38% prevalence of advanced fibrosis, the
      negative predictive value was 94% and positive predictive value was 63%. A biopsy
      length of > or = 2 cm was associated with higher concordance between FS results
      and liver fibrosis scores (P = 0.01). FS was clinically useful in ruling out
      advanced fibrosis in hepatitis C by identifying patients with mild disease in
      whom treatment could be deferred. The limitation of this test is its decreased
      sensitivity and specificity in the middle of the test's reporting range between
      scores of 0.42 and 0.80.

PMID- 16970597
TI  - Validation and comparison of indexes for fibrosis and cirrhosis prediction in
      chronic hepatitis C patients: proposal for a pragmatic approach classification
      without liver biopsies.
AB  - Noninvasive indexes have been developed to predict fibrosis staging. The aim of
      this study was to assess the diagnostic accuracy of these indexes in comparison
      with liver histology in hepatitis C virus (HCV)-infected patients. A total of 235
      consecutive patients with HCV infection from the Fibropaca multicentre
      independent study were included in this paper. FibroTest (FT), aspartate
      aminotransferase to platelet ratio index (APRI) and Forns score were assessed in
      the cohort and compared with liver histology performed on the same day. The main
      end point was the area under characteristic curves (AUCs) for the diagnosis of
      significant fibrosis (F2-F4) and cirrhosis (F4) by the METAVIR classification.
      Mean age was 46 (+/-11) years, 55% were males, 42% (n = 99) had significant
      fibrosis (F2-F4) and 7% (n = 16) had cirrhosis (F4). For the diagnosis of
      significant fibrosis, respective AUCs of FT, APRI and Forns score were 0.81 (95%
      confidence interval: 0.76-0.86), 0.71 (0.67-0.79) and 0.76 (0.70-0.82); for
      cirrhosis prognosis, AUCs of FT and APRI were 0.82 (0.77-0.87) and 0.81 (0.76
      0.86) (AUCs not significantly different). Using each index independently, all
      patients were classified by FT, 214 (91%) patients were classified by APRI and
      129 (55%) by Forns score. There were significantly more cases of discordances
      between APRI and liver biopsy than between FT or Forns score and liver biopsy (P
      < 0.05). Performing all scores (FT, Forns and APRI) without liver biopsy allowed
      fibrosis to be well evaluated in 191 patients (81.3%), including patients with FT
      failure. Liver biopsy remained mandatory to evaluate fibrosis in 44 patients
      (18.7%). Our study shows that performing all the tests and liver biopsy improves
      the diagnostic accuracy for liver fibrosis in chronic hepatitis C patients
      without patent comorbidities. The combination of all tests with liver biopsy
      allowed 225/235 (96%) patients to be correctly classified. The combination of all
      tests without liver biopsy allowed 191/235 (81.3%) patients to be correctly
      classified; liver biopsy remained mandatory in some patients (18.7%).

PMID- 16970598
TI  - Predictive value of serum globulin levels for the extent of hepatic fibrosis in
      patients with chronic hepatitis B infection.
AB  - The mechanism underlying disease progression in hepatitis B virus (HBV) infection
      is unknown. Immunoglobulins stimulate the proliferative activity of rat hepatic
      stellate cells in vitro. A strong association was found between serum
      immunoglobulin levels and hepatic fibrosis in patients with hepatitis C virus
      infection. Our objective was to determine if the same index could also be used in
      patients with chronic HBV infection. The records of 100 patients with
      biochemical, serological, virological and histological evidence of chronic HBV
      infection were reviewed for background factors and serum globulin and
      immunoglobulin levels. Mean (+/-SD) patient age was 44.0 +/- 14.7 years; 80 (80%)
      were male. Of the factors found to be significant on univariate analysis, the
      only significant predictors of severe hepatic fibrosis (stage > or = 2) on
      multivariate analysis were serum globulin level [odds ratio (OR) 5.97, 95%
      confidence intervals (CI) 1.82-19.53, P = 0.0004], platelet count (OR 0.98, CI
      0.97-0.99, P = 0.001), and immunoglobulin G (IgG) level (OR 1.003, CI 1.000
      1.007, P < 0.042) but not IgA, alkaline phosphatase, albumin or international
      normalized ratio. For each increase of 0.33 mg/dL in serum globulin, there was a
      0.5 point increase in the stage of hepatic fibrosis. There appears to be a strong
      association between levels of serum globulin and IgG and extent of hepatic
      fibrosis in patients with chronic HBV infection. They can serve as noninvasive
      markers of hepatic fibrosis and, if confirmed, have important implications for
      the management of patients with chronic HBV infection.

PMID- 16970599
TI  - Treatment of hepatitis C virus and human immunodeficiency virus coinfection: from
      large trials to real life.
AB  - To analyse the barriers for anti-hepatitis C virus (anti-HCV) treatment in human
      immunodeficiency virus (HIV)-HCV coinfected patients, we surveyed 71 physicians
      specializing in infectious disease (39%), internal medicine (27%), HIV/AIDS
      information and care (17%), haematology (10%) and hepatology (6%). A standard
      data collection form was used to identify patients observed in 7 days in November
      2004. Three hundred and eighty patients with the following characteristics were
      included: male gender 71%; mean age 41.5 years; HIV diagnosed 12 years ago;
      routes of transmission via injection drug use (78%); undetectable HIV viral load
      (235/373, 63%) or <10 000 copies/mL (86/373, 23%). HCV RNA was positive in 325 of
      369 (88%) patients; HCV genotype was 1 or 4 in 65% and liver biopsy had been
      carried out in 56%. There were several explanations for the nontreatment of HCV
      in 205 of the 380 (54%) patients, with 2.4 reasons per patient: anti-HCV
      treatment was deemed questionable (n = 109) because of minor hepatic lesions,
      alcohol consumption, or active drug use; no liver biopsy had been performed (n =
      68); treatment was contraindicated (n = 62), mainly for psychiatric reasons;
      there was physician conviction of poor patient compliance (n = 62) and patient
      refusal (n = 33). Patients having received anti-HCV treatment (n = 91) compared
      with those who had never received any (n = 205) were more commonly of European
      origin, had better control of their HIV infection, were followed by a
      hepatologist more often, had a liver biopsy more often and had more commonly a
      high HCV viral load (P < 0.001). In 'real life' in France in 2004, more than half
      of the HIV-HCV coinfected patients have never received anti-HCV treatment. The
      main reasons are a treatment that may be deemed questionable (minimal hepatic
      lesions, alcohol, active drug use), a lack of available liver biopsy, a
      psychiatric contraindication and physician conviction of poor patient compliance.

PMID- 16970600
TI  - Zidovudine use but not weight-based ribavirin dosing impacts anaemia during HCV
      treatment in HIV-infected persons.
AB  - Anaemia during peginterferon (PEG-IFN) and ribavirin (RBV) therapy is common in
      human immunodeficiency virus/hepatitis C virus (HIV/HCV)-coinfected patients
      despite the use of lower doses of RBV than are recommended for HIV-seronegative
      persons. In addition, concurrent zidovudine (ZDV) may exacerbate the anaemia
      caused by PEG-IFN and RBV. We retrospectively analysed the incidence of anaemia,
      RBV dose reduction and epoetin-alpha (EPO) use among coinfected patients treated
      with PEG-IFN and weight-based RBV (800-1400 mg/day) who enrolled in two clinical
      trials and had haemoglobin (Hb) levels assessed at baseline and after 4 and/or 12
      weeks of HCV treatment. Overall, 217 patients were included; pre-treatment Hb
      levels (mean 14.7 g/dL) were similar in all patients, including ZDV users (29% of
      patients). After 4 weeks of therapy, the mean Hb decline was greater among ZDV
      recipients (3.13 g/dL) compared with those on other anti-retroviral treatment
      (ART) (2.13 g/dL) or on no ART (1.47 g/dL) (P < 0.0001). RBV dose reduction and
      EPO use were more common in patients taking ZDV compared with those not taking
      ZDV (P < 0.0001). RBV dose was not associated with Hb reduction, RBV dose
      reduction or EPO use. Virologic response after 12 weeks of therapy and the
      treatment discontinuation rate did not differ by ZDV use. The use of ZDV but not
      weight-based RBV dosing was associated with an increased risk of anaemia, RBV
      dose reduction or EPO use in coinfected patients treated with PEG-IFN/RBV.
      However, ZDV use was not associated with higher rates of treatment
      discontinuation or lower early virologic response rates. HIV and hepatitis C care
      providers should be cognizant of these data.

PMID- 16970601
TI  - Expressional screening of interferon-stimulated genes for antiviral activity
      against hepatitis C virus replication.
AB  - Type-I interferons (IFNs) and the interferon-stimulated genes (ISGs) play a major
      role in antivirus responses against hepatitis C virus (HCV) infection. In this
      study, we studied expression profiles of ISGs in cells supporting subgenomic HCV
      replication (Huh7/Rep), and screened their activities to suppress HCV
      replication. Real-time PCR analyses showed that the expression levels of 23 ISGs
      were significantly lower in Huh7/Rep than naive Huh7 cells due to transcriptional
      suppression of the interferon-stimulated response element (ISRE). Furthermore,
      the expression level of ISGs was also decreased in the cured Huh7 cells in which
      replicon had been eliminated (cHuh7), indicating adaptation of the cells to
      support HCV replication by downregulating ISGs. On the other hand, expression of
      HCV replicon was significantly suppressed by overexpression of several ISGs
      including PKR, MxA, IRF-9, GBP-1, IFI-6-16, IFI-27, 25OAS and IRF-1. Knock down
      of GBP-1, IFI-6-16 and IFI-27 by short hairpin RNA resulted in increase of HCV
      replication. Thus, we conclude that downregulation of ISG expression is required
      in the host cells supporting HCV replication and that several ISGs directly
      suppress HCV replication. The search for ISGs that regulate HCV replication may
      help to elucidate the cellular antiviral defence mechanisms against HCV
      infection.

PMID- 16970602
TI  - Accurate model predicting sustained response at week 4 of therapy with pegylated
      interferon with ribavirin in patients with chronic hepatitis C.
AB  - Current models used to predict response to peginterferon plus ribavirin
      treatment, based on viral decline during the first 12 weeks of therapy, have
      focused on creating an early stopping rule to avoid unnecessary prolongation of
      therapy. We developed a multivariate model that predicted sustained virological
      response and nonresponse at baseline and during the first 12 weeks of therapy
      using collected data from 186 unselected patients with chronic hepatitis C
      treated with peginterferon plus ribavirin. This model employed ordinal regression
      with similarity least squares technology to assign the probability of a given
      outcome. Model variables include sex, age, prior treatment status, genotype,
      baseline serum alanine aminotransferase levels, histologic necroinflammation and
      fibrosis scores and serum hepatitis C virus RNA concentration at baseline and
      weeks, 4, 8, and 12. A multivariate model demonstrated high performance values at
      all time points. At baseline, the model demonstrated a negative predictive value
      (NPV) and a positive predictive value (PPV) of 91% and 95%, respectively. At week
      4, these values improved to 97% and 100%, respectively, with 95% sensitivity, 89%
      specificity and 93% accuracy. At week 4, the model was equally efficient for
      naive or previously treated patients. Internal validation demonstrated 90% PPV,
      94% NPV, 95% sensitivity, 88% specificity and 92% accuracy. A week 4 stopping
      rule for patients with chronic hepatitis C treated with peginterferon with
      ribavirin might be proposed by using the model developed in our study.

PMID- 16970603
TI  - Transient immunological control during acute hepatitis C virus infection: ex vivo
      analysis of helper T-cell responses.
AB  - Hepatitis C virus (HCV) readily sets up persistence after acute infection.
      Cellular immune responses are thought to play a major role in control of the
      virus. Failure of CD4+ T-cell responses in acute disease is associated with viral
      persistence but the dynamics of this are poorly understood. We aimed to assess
      such responses using a novel set of Class II tetrameric complexes (tetramers) to
      study helper T-cells ex vivo in acute disease. We analysed the HCV-specific CD4+
      T-cell response in a patient with acute hepatitis c infection. We were able to
      track the virus-specific CD4+ T-cells directly ex vivo with HLA DR4 tetramers.
      Proliferative responses were absent initially, recovered as viral load dropped
      and were lost again during relapse. Longitudinal tetramer analyses showed
      expanded populations of antiviral CD4+ T-cells throughout acute infection despite
      lack of proliferation. A pattern of transient CD4+ T-cell proliferative responses
      as HCV is partially controlled is observed. Failure to control virus is
      associated with emergence of 'dysfunctional' CD4+ T-cell populations. Failure to
      control HCV in acute disease may relate to the capacity to sustain efficient
      immune responses as virus attempts to 'bounce back' after partial control.

PMID- 16970604
TI  - Linking behavioral ecology with population genetics: insights from Drosophila
      nigrospiracula.
AB  - Although Drosophila species provide important model systems for evolutionary
      biology, the ecologies and natural histories of most species are insufficiently
      characterized to permit predictions with respect to issues such as population
      genetic structure. A notable exception is the group of cactophilic Drosophila
      endemic to the Sonoran Desert of North America. One of these species, D.
      nigrospiracula, exhibits no population subdivision anywhere in its range. Here we
      present evidence suggesting that the timing of mating in relation to dispersal
      contributes to the panmixia observed in this species.

PMID- 16970605
TI  - Population structure in Ascaris suum (Nematoda) among domestic swine in Denmark
      as measured by whole genome DNA fingerprinting.
AB  - We here analyze the population structure in the pig roundworm, Ascaris suum,
      among domestic pigs in Denmark using a whole-genome DNA fingerprinting technique,
      "amplified fragment length polymorphism" (AFLP) analysis. With these data, we can
      extract absolute gene frequency variance components and G-statistics for 135
      independent nucleotide polymorphisms. The average proportion of total variance
      partitioned between Jutland and Zealand is less than 3% of the total variance,
      implying no restriction in gene flow between worms from different regions in
      Denmark. The average gene frequency difference between two farms widely separated
      in Jutland represents 5% of the total genetic variance of these two farms
      combined. Conversely, worms from different hosts within these two farms are more
      subdivided, with an average of 12% of the total variance in gene frequencies
      within farms being distributed between hosts. This result implies substantial
      single generation inbreeding due to founder effects in the establishment of adult
      worms in single hosts. Absolute variance components extracted from the gene
      diversities also showed significant differences, with the among-host variance
      being greater that the between-farm and between-region values. This little
      geographical variation is discussed in relation to the hierarchic structure of
      the Danish swine production system. Comparison of our results with other studies
      on parasitic roundworms, suggests that patterns of host dispersal effectively
      control patterns of worm gene flow. Furthermore, the potential spread of
      anthelminth resistance among A. suum may thus be rapid, due to the flow of
      infected hosts within the domestic swine stocks in Denmark.

PMID- 16970606
TI  - Cytogenetic analysis of three Italian populations of Coregonus lavaretus (Pisces,
      Salmoniformes) with chromosomal localization of major and minor ribosomal genes,
      and telomeric repeats.
AB  - The European whitefish, Coregonus lavaretus, widely distributed in freshwater of
      northern Europe and introduced into the major lakes of northern Italy, has been
      restocked in central Italian lakes. In accordance with current managing
      practices, a reduced number of spawners contribute to reproduction within each
      lake and a certain degree of isolation is to be expected between populations from
      different lakes, resulting in the rapid fixing of chromosomal changes. A detailed
      survey of three populations from different lakes was carried out using classical
      and molecular cytogenetic techniques, to verify if specific chromosomal markers
      are present in the distinct populations. The comparative analysis revealed
      intraspecific variability of NORs and fixed differences in their number in the
      three populations. A co-localization of major and minor rRNA genes on one
      chromosome site was also observed. The original data regarding the chromosome
      mapping of the (TTAGGG)(n) telomeric repeat obtained in this study, demonstrated
      their exclusively terminal distribution, and a conspicuous inter-chromosomal
      variation in the number of repeats. The results are compared with data available
      for populations from native geographic ranges.

PMID- 16970607
TI  - Co-precipitation of protein and polyester as a method to isolate high molecular
      weight DNA.
AB  - DNA isolation is often the limiting step in genetic analysis using PCR and
      automated fragment analysis due to low quality or purity of DNA, the need to
      determine and adjust DNA concentrations after isolation etc. Several protocols
      have been developed which are either safe and provide good quality DNA or
      hazardous and provide excellent quality DNA. In this brief communication I
      describe a new and rapid method of DNA isolation which employs the co
      precipitation of protein and polyester, in the presence of acetone, to remove
      contaminating proteins from a lysed-tissue sample, thus leaving high quality pure
      DNA. The advantages of this method are increased safety over the
      phenol:chloroform and the chaotrophic salt methods and increased purity over the
      salting-out method. Since the concentrations of DNA isolated using this method
      are relatively consistent regardless of the amount of starting tissue (within
      limits), adjustments of the DNA concentrations before use as templates in PCR's
      are not necessary.

PMID- 16970608
TI  - PCR-RFLP analysis of cpDNA and mtDNA in the genus Houttuynia in some areas of
      China.
AB  - Plasmon diversity of 70 Houttuynia Thunb. accessions were investigated by using
      PCR-RFLP technology. The results not only revealed the interspecific, but also
      intraspecific plasmon variations within the genus Houttuynia. In total, 59
      distinct organelle haplotypes were identified among 70 accessions, two in H.
      emeiensis and 57 in H. cordata. The average genetic similarities (GSs) values
      within H. emeiensis and H. cordata accessions were 0.986 and 0.950, respectively.
      The intraspecific GS value between H. emeiensis and H. cordata was 0.951. Two
      accessions of the new species H. emeiensis, W01-1 and W01-86, were very closely
      clustered together, but they could not be completely separated from H. cordata
      according to the cluster analysis. The results suggest that the classification of
      new species could be reconsidered. The level of genetic diversity between
      cultivated and wild groups in H. cordata was very low. The groups based on
      plasmon PCR-RFLP GS were little related with geographic distribution and
      chromosome number. We also discuss the phylogenetic relationship and
      phylogeographic information of the genus Houttuynia.

PMID- 16970609
TI  - Microsatellite markers confirm high apomixis level in cassava bred clones.
AB  - Apomixis genes have successfully been transferred to cassava by hybridization
      with the wild species, Manihot glaziovii. The interspecific hybrid of cassava and
      M. glaziovii was left for open pollination during the subsequent three
      generations. Seven sibs and their maternal progenitor of the fourth generation
      were genotyped using five microsatellite loci previously developed for cassava.
      All sibs were identical with each other and with their maternal progenitor. Sibs
      from M. glaziovii itself proved to be identical when examined by the same
      microsatellite loci. These results lead to the conclusion that apomixis do occur
      in wild cassava relatives and apparently has played an important role in Manihot
      speciation.

PMID- 16970610
TI  - Ribosomal DNA intergenic spacer sequence in foxtail millet, Setaria italica (L.)
      P. Beauv. and its characterization and application to typing of foxtail millet
      landraces.
AB  - We determined the sequence of ribosomal DNA (rDNA) intergenic spacer (IGS) of
      foxtail millet isolated in our previous study, and identified subrepeats in the
      polymorphic region. We also developed a PCR-based method for identifying rDNA
      types based on sequence information and assessed 153 accessions of foxtail
      millet. Results were congruent with our previous works. This study provides new
      findings regarding the geographical distribution of rDNA variants. This new
      method facilitates analyses of numerous foxtail millet accessions. It is helpful
      for typing of foxtail millet germplasms and elucidating the evolution of this
      millet.

PMID- 16970611
TI  - Cytological affinities and interfertilities between Lolium temulentum and L.
      persicum (Poaceae) accessions.
AB  - Interspecific crossing between L. temulentum L. and L. persicum Boiss. & Hohen.
      ex Boiss. was performed to clarify their interfertility based on the results of
      chromosome pairing, pollen fertility and seed set. Both parents were normal with
      a high percentage of chromosome association of ring bivalents in contrast to rod
      bivalents at metaphase I, pollen fertility and seed set, but F1 hybrids showed
      different proportions of them for each crossing combination. Chromosome affinity
      expressed by pairing was certainly a factor affecting the pollen fertility or
      seed set in F1 hybrids, but it was not the most important. The positive
      correlation was generally found between pollen fertility and seed set of F1
      hybrids. The L. persicum accession with relatively high interfertility with L.
      temulentum was supposed to be derived from natural hybridization between L.
      temulentum and L. persicum. The degree of cytogenetic differentiation between L.
      temulentum and L. persicum existed because of lower chromosomal pairing, pollen
      fertility and seed set, but their F1 hybrids were partially fertile.

PMID- 16970612
TI  - Sympatry, allopatry and sexual isolation between Drosophila mojavensis and D.
      arizonae.
AB  - Populations of the North American cactophilic fruitfly Drosophila mojavensis and
      its sibling species D. arizonae exist both in sympatry and in allopatry. Females
      of D. arizonae, regardless of their population of origin, are effectively
      completely isolated behaviorally from D. mojavensis males. On the other hand,
      females of D. mojavensis from the sympatric populations in Sonora, Mexico exhibit
      significantly stronger premating isolation from D. arizonae males than do D.
      mojavensis females from allopatric populations from the Baja California
      peninsula. Earlier studies interpreted these limited observations as support for
      reinforcement. Since the time of those studies, additional allopatric populations
      of D. mojavensis have been collected from southern California and from Santa
      Catalina Island, off the coast of southern California. Here, we tested the
      prediction that if sympatry is in fact associated with increased isolation in D.
      mojavensis, these additional allopatric populations also should show, relative to
      the sympatric ones, less isolation from D. arizonae. Our results are consistent
      with this prediction and suggest that isolation is in fact stronger in sympatry.

PMID- 16970613
TI  - Characterization of HMW prolamines and their coding sequences from Crithopsis
      delileana.
AB  - The high-molecular-weight (HMW) prolamines subunits and their coding sequences
      from wheat-related diploid species Crithopsis delileana were investigated. Only
      one HMW prolamine subunit with the similar electrophoresis mobility to the y-type
      HMW glutenin subunit of hexaploid wheat was observed in two accessions of C.
      delileana by SDS-PAGE analyses of the total storage protein fractions. It was
      confirmed by sequencing and expression analysis that this prolamine subunit was
      an x-type subunit. The amino acid sequence of this subunit had the similar
      typical structure to those of x-type HMW glutenin genes previously described in
      wheat. An in-frame stop codon was found in the coding sequences of y-type
      prolamine subunits. It was found by specifically extraction of HMW prolamines and
      sequence analysis that the coding regions of Ky prolamine subunit gene is very
      likely to be not expressed as a full-length protein. Phylogenetic analysis
      indicated that the Kx subunit could be clustered together with 1Ax1 subunit by an
      interior paralleled branch, and Ky subunit (inactive) was most closely related to
      the 1Ay subunit. The coding sequences of Kx subunit could successfully be
      expressed in bacterial expression system, and the expressed protein had the same
      electrophoresis mobility as the Kx subunit from the seed of C. delileana. It was
      the first time that the HMW prolamines subunits encoded by K genome of C.
      delileana were characterized.

PMID- 16970614
TI  - Application of antisense transformation of a barley chitinase in studies of
      arbuscule formation by a mycorrhizal fungus.
AB  - Barley (Hordeum vulgare L.) plants of two commercial cultivars were transformed
      with sense and antisense constructs of a chitinase class II gene in order to
      develop a transformation system for this gene in barley. Transformation of
      embryos with the two antisense constructs resulted in ten regenerated plants,
      while no plants could be obtained using the sense construct. The presence of the
      inserted construct could be confirmed for six of the plants by PCR analysis. This
      system was used to study the role of class II chitinase in the regulation of
      mycorrhizal symbiosis. The colonization of two of the antisense transformants by
      the arbuscular mycorrhizal fungus Glomus intraradices was investigated
      microscopically and by use of signature fatty acids. The arbuscular incidence
      increased in transformed barley, and one transformant supported higher
      extraradical mycelium biomass. It is concluded that antisense transformation of
      barley could be a useful tool in investigations on the symbiosis between barley
      and mycorrhizal fungi.

PMID- 16970615
TI  - Fluorescence in situ hybridization of rDNA, telomeric (TTAGGG)n and (GATA)n
      repeats in the red abalone Haliotis rufescens (Archaeogastropoda: Haliotidae).
AB  - The physical location of 18S-5.8S-28S rDNA, telomeric sequences with (TTAGGG)n
      DNA probe and (GATA)n microsatellites were performed by fluorescence in situ
      hybridization in chromosomes of red abalone Haliotis rufescens. The karyotype of
      red abalone showed a diploid number of 36 (8M+9SM+1ST). FISH performed with rDNA
      probe, showed the location of major ribosomal clusters in the terminal region of
      the large arms of two submetacentric pairs (chromosome 4 and 5). Localization of
      heteromorphisms of FISH-rDNA was found between chromosome homologues and sister
      chromatids in all metaphases analyzed. This indicates that rDNA clusters are
      variable within the red abalone genome. The variability in the NOR-bearing
      reported using silver staining in other gastropods and our result are discussed.
      In addition, the presence of microsatellite (TTAGGG)n and (GATA)n was
      demonstrated after FISH treatment by DNA probes. The telomeric sequence occurred
      at the ends of all mitotic chromosomes, while the (GATA)n repetitive was found on
      chromosomal interstitial zones as well as at the telomeres in abalone
      chromosomes.

PMID- 16970616
TI  - Molecular cytogenetic characterization and disease resistance observation of
      wheat-Dasypyrum breviaristatum partial amphiploid and its derivatives.
AB  - A wheat-Dasypyrum breviaristatum partial amphiploid and its derivatives were
      analyzed by molecular cytological observation and tested for disease resistance
      in order to evaluate the potential use of the D. breviaristatum for wheat
      improvement. A fertility-improved partial amphiploid, TDH-2, was produced from
      the selfing population of Triticum aestivum cv. Chinese spring (CS)-D.
      breviaristatum amphiploid. Based on the results obtained from genomic in situ
      hybridization (GISH) and seed protein electrophoresis, we found the presence of
      fourteen D. breviaristatum chromosomes and the absence of D genome in TDH-2,
      indicating that the genomic composition of TDH-2 was AABBV(b)V(b). GISH analysis
      on BC(1)F(4) progenies of TDH-2xwheat demonstrated that alien D. breviaristatum
      chromosomes or segments were frequently transmitted. A survey of diseases
      resistance revealed that powdery mildew resistance from D. breviaristatum was
      totally expressed, however, the expression of stripe rust resistance from D.
      breviaristatum was dependent on the wheat background. The comparison of
      polymerase chain reaction (PCR), which was carried out using molecular marker
      SCAR(1400) linked to Pm21 D. villosum-derived powdery mildew resistance gene,
      suggested that D. breviaristatum possessed new resistance gene(s) different from
      that in D. villosum. The present study showed that the partial amphiploid TDH-2
      and its derivatives could serve as novel sources for transfer of disease
      resistance genes to wheat.

PMID- 16970617
TI  - Microsatellite markers for powdery mildew resistance in pea (Pisum sativum L.).
AB  - Powdery mildew is a common disease of field pea, Pisum sativum L., and is caused
      by the ascomycete fungus Erysiphe pisi. It can cause severe damage in areas where
      pea is cultivated. Today breeders want to develop new pea lines that are
      resistant to the disease. To make the breeding process more efficient, it is
      desirable to find genetic markers for use in a marker-assisted selection (MAS)
      strategy. In this study, microsatellites (SSR) were used to find markers linked
      to powdery mildew resistance. The resistant pea cultivar '955180' and the
      susceptible pea cultivar 'Majoret' were crossed and F2 plants were screened with
      SSR markers, using bulked segregant analysis. A total of 315 SSR markers were
      screened out of which five showed linkage to the powdery mildew resistance gene.
      No single marker was considered optimal for inclusion in a MAS program. Instead,
      two of the markers can be used in combination, which would result in only 1.6%
      incorrectly identified plants. Thus SSR markers can be successfully used in
      marker-assisted selection for powdery mildew resistance breeding in pea.

PMID- 16970618
TI  - Morphological and molecular characterization of a new frizzy panicle mutant, "fzp
      9(t)", in rice (Oryza sativa L.).
AB  - The spikelet identity gene "fzp" (frizzy panicle) is required for transformation
      of the floral meristems to inflorescent shoots. In fzp mutants, spikelets are
      replaced by branches and spikelet meristems produce massive numbers of branch
      meristems. We have isolated and characterized a new fzp mutant derived from
      anther culture lines in rice and designated as fzp-9(t). The fzp-9(t) mutant
      showed retarded growth habit and developed fewer tillers than those of the wild
      type plant. The primary and secondary rachis branches of fzp-9(t) appeared to be
      normal, but higher-order branches formed continuous bract-like structures without
      developing spikelets. The genetic segregation of fzp-9(t) showed a good fit to
      the expected ratio of 3: 1. The sequence analysis of fzp-9(t) revealed that there
      is a single nucleotide base change upstream of the ERF (ethylene-responsive
      element-binding factor) domain compare to wild-type plant. The mutation point of
      fzp-9(t) (W66G) was one of the six amino acids of the ERF domain that contributed
      to GCC box-specific binding. The premature formation of a stop codon at the
      beginning of the ERF domain might cause a non-functional product.

PMID- 16970619
TI  - Contested memory: debates over the nature of Mendel's paradigm.

PMID- 16970620
TI  - Polymorphism study of seven SNPs at ADH genes in 15 Chinese populations.
AB  - It has been shown that the variants of alcohol dehydrogenase (ADH) genes exhibit
      great diversities among various populations and are associated with
      susceptibility to alcoholism. To investigate the distribution of SNPs at ADH
      genes in Chinese populations and the genetic relationship of these groups, we
      collected 467 individuals from 15 groups distributing widely from north to south
      in China and genotyped 7 SNPs at ADH genes respectively. The statistic analyses
      of allele frequencies, estimated haplotype frequencies, pairwise linkage
      disequilibrium, AMOVA (analysis of molecular variance), pairwise Fst', and
      cluster analysis indicated (1) that six of these seven SNPs showed great
      variations in the 15 Chinese populations, and three of them (RsaI, SspI, EcoRI),
      were confirmed to be informative SNPs. However, the causative SNP ADH1B Arg47His
      confirmed in case-control studies could not act as significant indicator to
      distinguish bibulous groups from non-bibulous groups in healthy individuals; (2)
      haplotypes constructed with ADH SNPs could be used as markers to discern
      different populations in China, and six-allele haplotype "221211" was the most
      common one defined in present study; (3) on the basis of SNPs analysis of ADH
      genes, the 15 populations were grouped into northern groups and southern groups.
      Moreover, the origin relationship among the populations was indicated according
      to the results of cluster analysis.

PMID- 16970621
TI  - Periodontal therapy in siblings with Papillon-Lefevre syndrome and tinea capitis:
      a report of two cases.
AB  - OBJECTIVE: Report of clinical and microbiological periodontal findings before and
      6 months after treatment of two siblings with Papillon-Lefevre syndrome (PLS) and
      tinea capitis. METHODS: Two brothers, RG 3 years and NG 5 years of age, were
      referred for treatment due to premature mobility of their deciduous teeth.
      Probing depths (PPD), attachment levels (PAL-V), and furcation involvements were
      examined clinically. Panoramic radiographs were taken. Subgingival plaque samples
      within the deepest pocket of each tooth were taken and analysed by real-time
      polymerase chain reaction (PCR) for Actinobacillus actinomycetemcomitans (AA),
      Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola,
      Fusobacterium nucleatum, and Prevotella intermedia. One-stage full-mouth scaling
      and extraction of hopeless teeth were performed under general anaesthesia,
      followed by systemic amoxicillin and metronidazole for 7 days. Clinical and
      microbiological analyses were performed 6 months after treatment. RESULTS: Before
      treatment, both siblings had exhibited PPD of up to 13 mm, Class III furcation
      defects at four teeth, and marginal suppuration. AA was detected in both patients
      and at all teeth at levels ranging from 3.0 x 10(2) to 5.1 x 10(6). Both patients
      exhibited palmar and plantar hyperkeratosis. Seven teeth were extracted from RG,
      and nine from NG. Six months after treatment, PPD had been reduced to <or=5 mm.
      AA was not detected in any of the remaining teeth. CONCLUSION: Even periodontally
      affected deciduous teeth of PLS patients can be treated successfully. Suppression
      of AA to below detection level seems to be of high significance.

PMID- 16970622
TI  - Enamel matrix derivative versus guided tissue regeneration in the presence of
      nicotine: a histomorphometric study in dogs.
AB  - AIM: The goal of this histometric study was to compare the healing process of
      dehiscence-type defects treated by enamel matrix derivative (EMD) or guided
      tissue regeneration (GTR) under the effect of nicotine in the dog model.
      MATERIALS AND METHODS: Eight mongrel dogs were used. Buccal osseous dehiscences
      were surgically created on the mesial roots of the mandibular third and fourth
      pre-molars. The defects were exposed to plaque accumulation for 3 months. After
      this period, the defects were randomly assigned to one of the treatments: open
      flap debridement (OFD), EMD or GTR with a resorbable membrane. During 4 months,
      the dogs received subcutaneous administration of nicotine (2 mg/kg twice a day
      with a 12 h interval between the applications). After this period, the animals
      were killed and the blocks were processed. The histometric parameters evaluated
      included gingival recession, epithelial length, connective tissue adaptation, new
      cementum and new bone. RESULTS: A superior length of new cementum was observed in
      the sites treated by EMD in comparison with OFD (p< or =0.05). No statistically
      significant differences were observed between GTR and the other groups.
      CONCLUSIONS: In the presence of nicotine, EMD may promote more new cementum
      formation than OFD while GTR failed to provide a significant difference.

PMID- 16970624
TI  - Periodontal parameters and platelet-activating factor levels in serum and
      gingival crevicular fluid in a Chinese population.
AB  - AIM: Platelet-activating factor (PAF) is a potent proinflammatory mediator and
      has been implicated in cardiovascular pathophysiology. The present clinical study
      assessed the relation between the severity of periodontal disease and PAF levels
      in gingival crevicular fluid (GCF) and serum. METHODS: A total of 60 non-smoking
      subjects (21 periodontitis, 19 gingivitis patients and 20 healthy individuals)
      were included. Probing depth, attachment level, bleeding on probing, plaque index
      and sulphide levels were recorded at six sites of each tooth. GCF and blood
      samples were collected from all individuals, and PAF levels were investigated by
      enzyme-linked immunoabsorbent assay. RESULTS: The periodontitis group showed
      significantly higher PAF levels in the serum (329.3+/-287.3 pg/ml) and GCF
      (21.8+/-7.0 pg/sample) compared with the gingivitis group (138.0+/-77.9 pg/ml,
      13.8+/-3.6 pg/sample) and with healthy controls (68.9+/-42.8 pg/ml, 2.4+/-2.7
      pg/sample). The differences between patients and controls were statistically
      significant (p<or=0.05). Positive correlations were observed between PAF levels
      in GCF and serum and for PAF levels and clinical parameters. CONCLUSION: The
      present findings suggest a role of PAF in the pathogenesis of periodontitis.
      Based on the observed close correlation of GCF and serum PAF levels, future
      studies are warranted to test the hypothesis of a possible link between
      periodontitis and adverse systemic events mediated by PAF.

PMID- 16970623
TI  - Dental restorations: a risk factor for periodontal attachment loss?
AB  - BACKGROUND: Dental caries and restorations in proximal tooth surfaces often
      impinge upon the periodontal biological width. AIM: This study examines whether
      these factors may contribute to risk for periodontal attachment loss at these
      sites. METHODS: The study is based upon data from the Dunedin Multidisciplinary
      Health and Development Study, a long-standing cohort study. Approximal tooth
      surfaces of 884 study members were evaluated for restorations and caries at age
      26 and again at 32 years, and probing depth and gingival recession were recorded
      in millimetres at age 32. Attachment loss was computed as the sum of pocket depth
      and gingival recession. Data were analysed using generalized estimating
      equations. RESULTS: Where a caries/restorative event had occurred on an inter
      proximal tooth surface before age 26, the age-32 attachment loss at the
      corresponding periodontal site was approximately twice more likely to be >or=3 mm
      than if the adjacent tooth surface had remained sound to age 32. This was also
      true where a caries/restorative event had occurred subsequent to age 26. The
      association remained after controlling for potential confounders, including
      smoking. CONCLUSIONS: Site-specific periodontal attachment loss due to dental
      caries or restorative events occurs in adults in their third and fourth decades
      of life.

PMID- 16970625
TI  - Possible association between mother's periodontal status and preterm delivery.
AB  - BACKGROUND: A case-control study was undertaken to detect whether initial chronic
      localized periodontitis could be a risk factor for preterm birth (PB) and foetal
      growth restriction. METHODS: A PB case was defined if a patient had a threatening
      premature event during pregnancy pre-term premature rupture of membranes, or
      spontaneous pre-term delivery, before the 37th week of pregnancy, and/or the
      weight of the newborn was <2500 g. Into the PB (case) group, 77 women were
      allocated, while 84 were included in the control group, all of whom had delivery
      after the 37th gestational week and with a newborn weighing >or=2500 g. RESULTS:
      A significant association was found between PB and initial chronic localized
      periodontitis, the criteria being bleeding at >or=50% of the examined teeth and
      having at least at one site at >or=4 mm probing depth (p=0.0001). The adjusted
      odds ratio for initial chronic localized periodontitis was 3.32, 95% CI: 1.64
      6.69. The average weight of newborns of mothers with periodontitis was
      significantly less than that of the women without periodontitis (p=0.002).
      CONCLUSIONS: The results support the hypothesis that initial chronic localized
      periodontitis of pregnant women could lead to PB, and birth-weight reduction.

PMID- 16970626
TI  - Evidence for different nutrient partitioning in Boran (Bos indicus) and Boran x
      Holstein cows when re-allocated from low to high or from high to low feeding
      level.
AB  - This study tested the hypothesis that purebred Boran (Bos indicus) cows and
      crossbreds of Boran and Holstein respond differently to long-term changes of
      feeding level in nutrient partitioning to milk and body fat stores. A total of 27
      cows of these two genotypes were subjected either to a low or a high feeding
      level from their first oestrus as heifers until birth of their third calf. Half
      of the cows of each genotype were then switched to the other feeding level during
      the third reproduction cycle. If at all, Boran cows responded to a change in the
      feeding level almost exclusively by a corresponding change in body weight but not
      milk yield. Crossbred cows kept continuously on the low feeding level had a lower
      milk yield than those continuously fed the high level, but lost similar amounts
      of body weight. In crossbred cows, changing the feeding level from high to low
      was accompanied by a mobilization of body reserves, whereas a change from low to
      high level resulted mostly in an increase in milk yield. Certain other genotype
      differences in metabolic response were obvious from differences in body
      composition and from the metabolic profile either reflected in blood
      (particularly insulin-like growth factor I) or in adipose tissue (lipoprotein
      lipase). Reproductive performance differed between genotypes, with shorter
      lactations associated with earlier occurrences of the first oestrus in the Boran
      cows. Generally, feeding history appeared to have at least as much influence on
      energy partitioning as the actual feeding level. In conclusion, purebred Boran
      cows seem to react to long-term food fluctuations mainly by mobilizing and
      restoring body fat reserves, whereas cows crossbred with Holstein tend to spend
      extra energy preferentially for milk production.

PMID- 16970627
TI  - Pharmacokinetic/pharmacodynamic modelling of roxithromycin for the inhibitory
      effect of tumour necrosis factor-alpha and interleukin-6 production in dogs.
AB  - The objective of the present study was to determine and characterize the
      relationship between the plasma concentration of roxithromycin, and its
      inhibitory effect on cytokine production, in order to predict its possible
      clinical relevance. Six healthy beagle dogs received a single intravenous dose of
      20-mg roxithromycin per kg body weight. Blood samples were obtained at different
      time points. The plasma was analysed with respect to roxithromycin, tumour
      necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). The concentration
      effect relationship was explored by modelling the data using two compartmental
      model and an indirect response model with an E(max) concentration-effect
      relationship. The estimated pharmacokinetic parameters (geometric mean) were as
      follows: V(c) = 2.59 l; k(10) = 0.08/h; k(12) = 0.26/h; k(21) = 0.40/h. The
      pharmacodynamic parameters (geometric mean) for the inhibitory effect on cytokine
      production induced by heat-killed Staphylococcus aureus (HKSA) were for TNF-alpha
      (k(in) = 1.42 microg/h; k(out) = 1.10 microg/h; EC(50) > 5.69 mg/l) and for IL-6
      (k(in) = 2.31 microg/h; k(out) = 2.04 microg/h; EC(50) = 21.07 mg/l) production,
      respectively. The inhibitory effect of roxithromycin on production can be
      adequately described by the indirect response model with an E(max) concentration
      effect relationship.

PMID- 16970628
TI  - Effect of copper deficiency on blood lipid profile and haematological parameters
      in broilers.
AB  - The aim of the study was to observe the changes in haematological parameters and
      blood lipid profile through copper (Cu) deficiency. Eighty broiler chicks were
      used in the study. The chicks were separated into two equal groups (n = 40), feed
      treatment according to the groups started on day 7. The animals in the control
      group were fed with normal feed. Those in the Cu-deficient group were fed with
      feed that did not contain supplemental Cu. Blood samples were taken from all the
      animals on days 7, 21 and 49. Fibrinogen and prothrombin time were assayed in
      plasma; total cholesterol, high density lipoprotein cholesterol, low density
      lipoprotein cholesterol (LDL-cholesterol), triglyceride and ceruloplasmin were
      assayed in sera; and haematocrit and thrombocyte levels were assayed in the blood
      samples. Total cholesterol, triglyceride and LDL-cholesterol levels were
      significantly higher in the Cu-deficient group than in the control group. Serum
      ceruloplasmin levels were lower in the Cu-deficient group than in the control
      group. Prothrombin time was higher in the Cu-deficient group than in the control
      group. Haematocrit levels were lower in the Cu-deficient group than in the
      control group. It was concluded that Cu deficiency created hypertriglyceridaemia,
      hypercholesterolaemia, insufficient growth and anaemia in broilers.

PMID- 16970629
TI  - Pathology of Trichuris suis infection in pigs fed an inulin- and a non-inulin
      containing diet.
AB  - Pathology of the colon in pigs infected with Trichuris suis and fed an inulin and
      a non-inulin containing diet was studied to investigate the inflammatory response
      induced and the influence of inulin on this. Twenty-nine pigs were allocated into
      four groups (N-7, I-7, N-9 and N/I-9). Groups N-7, N-9 and N/I-9 were given a
      diet with non-fermentable carbohydrates, and group I-7 was fed a diet including
      fermentable carbohydrates (inulin). After 2 weeks, all pigs were inoculated with
      2000 T. suis eggs. Seven weeks post-infection (p.i.), groups N-7 and I-7 were
      killed and group N/I-9 changed to inulin diet to study the influence of inulin on
      already established T. suis. Nine weeks p.i., groups N-9 and N/I-9 were killed.
      Trichuris suis were collected from the colon for enumeration. Tissues from the
      colon of each pig were taken for histological and immunohistochemical
      quantitative and semi-quantitative evaluations of heterophils, eosinophils, mast
      cells, IgA(+), IgG(+), IgM(+) and CD3(+) cells. The findings were compared with
      tissues from seven uninfected pigs of the same age. Pigs fed inulin had
      significantly fewer worms compared with pigs on the non-fermentable carbohydrate
      diet. The number of inflammatory cells in the colonic mucosa was increased in all
      T. suis-infected pigs compared with uninfected controls. The numbers of
      eosinophils, mast cells, IgA(+), IgG(+) and CD3(+) cells were significantly lower
      in pigs fed inulin than pigs fed non-fermentable carbohydrate. Whether this is a
      direct effect of inulin or a secondary effect due to the lower parasitic burden
      in inulin fed pigs is not known.

PMID- 16970630
TI  - Influence of Escherichia coli endotoxin-induced endotoxaemia on the
      pharmacokinetics of enrofloxacin after intravenous administration in rabbits.
AB  - The main goal of present study was to determine the effects of an Escherichia
      coli endotoxin-induced endotoxaemic status on disposition of enrofloxacin after a
      single intravenous dose (5 mg/kg) in rabbits. Septic shock was induced by the
      i.v. bolus administration at a single dose of E. coli lipopolysaccharide. Six
      adult New Zealand White rabbits were used. Concentrations of drug in plasma were
      determined by HPLC. The plasma pharmacokinetic values for enrofloxacin were best
      represented using a two-compartment open model. Total plasma clearance (Cl(T))
      decreased from 2.11 (l/h/kg) in healthy animals to 1.50 (l/h/kg) in rabbits with
      septic shock, which is related to an increase in the AUC(0-->infinity). In
      endotoxaemic rabbits, volume of distribution at steady state (V(dss) = 3.61 l/kg)
      was significantly lower (P < 0.05) than in healthy animals (V(dss) = 4.97 l/kg).
      However, the elimination half-life of enrofloxacin was not affected by
      lipopolysaccharide administration.

PMID- 16970631
TI  - Influence of anaesthesia on canine hip dysplasia score.
AB  - Hip dysplasia (HD) scores, based on the five grades, as defined by the Federation
      Cynologique Internationale, were compared between anaesthetized (group 1, n =
      3839) and non-sedated non-anaesthetized dogs (group 2, n = 1517). Each dog was
      radiographed in the standard ventro-dorsal hip joint extended position. Each
      radiograph was evaluated by the same reader blinded regarding the dog's status of
      anaesthesia. Results showed that there was a significant difference in hip
      dysplasia prevalence between group 1 (22%) compared with group 2 (9%) (P <
      0.005). This difference was the result of a lower rate of hip-joint laxity
      assessment and the measurement of Norberg-Olsson angle <105 degrees in group 2
      compared with group 1. The acetabular and femoral morphologies were not
      significantly different between the groups. The data confirm that the scoring of
      dogs for HD on standard radiographs with the hip joints extended is influenced by
      anaesthesia.

PMID- 16970632
TI  - A comparative randomized field trial on intramammary and intramuscular dry cow
      antibiotic treatment of subclinical Staphylococcus aureus mastitis in dairy cows.
AB  - The efficacy of two dry cow treatment (DCT) regimens for subclinical
      Staphylococcus aureus mastitis was evaluated in naturally infected dairy cows. At
      dry-off, cows were assigned to two treatment groups by randomized blocks on the
      basis of parity and somatic cell count (SCC). Two antibiotic DCT regimens were
      used, namely: (1) a single intramammary infusion containing sodium nafcillin,
      procaine benzylpenicillin and dihydrostreptomycin; and (2) systemic cefquinome
      administered intramuscularly, twice at a 24-h interval. In the intramammary (IMM)
      treatment group, the S. aureus intramammary infection (IMI) rate was reduced from
      40% (56/140 quarters) before dry-off to 20% (28/140) after calving. Seventy per
      cent (39/56) of the S. aureus-positive quarters were negative after calving, and
      13% (11/84) of the negative quarters were positive after calving. In the systemic
      treatment group, the S. aureus IMI rate increased from 39% (29/74 quarters)
      before dry-off to 55% (41/74) after calving. Twenty-eight per cent (8/29) of the
      S. aureus-positive quarters were negative after calving and 45% (20/45) of the
      negative quarters were positive after calving. The odds ratio of an S. aureus
      positive quarter being negative after calving in the IMM group relative to the
      systemic therapy group was 44.6 (95% confidence interval = 2.1-909.1, P < 0.01).
      Parity, quarter, milk SCC and N-acetyl-beta-D-glucosaminidase were tested in the
      model, and were found to have no significant effect on S. aureus cure rates or
      new IMI rates. The IMM treatment resulted in a higher cure rate compared with
      that observed in previous studies. The very low cure rate after systemic
      cefquinome treatment was comparable to the spontaneous cure rate observed in
      untreated controls in previous studies. The unfavourable results of the
      cefquinome systemic DCT might reflect inadequate pharmacokinetic properties of
      the drug regarding poor udder penetration in subclinical mastitis and short
      antimicrobial effect compared with the IMM treatment.

PMID- 16970633
TI  - Xylazine, ketamine and their combination for lumbar epidural analgesia in water
      buffalo calves (Bubalus bubalis).
AB  - The study was conducted to evaluate the effects of xylazine individually (0.05
      mg/kg), ketamine individually (2.5 mg/kg), and a combination of xylazine and
      ketamine (0.05 mg/kg and 2.5 mg/kg) after lumbar epidural administration in water
      buffalo calves. Fifteen non-descript, male water buffalo calves of 6-8 months of
      age weighing between 55 and 75 kg were randomly placed in three groups (groups A,
      B and C). The agents were administered at the first lumbar epidural space.
      Clinico-physiological parameters, such as analgesia, ataxia, sedation,
      salivation, heart rate, respiratory rate and rectal temperature were studied.
      Other haematological and biochemical parameters monitored were haemoglobin,
      packed cell volume, total leukocyte count, plasma glucose, cortisol, protein
      albumin, globulin, blood urea nitrogen (BUN), creatinine, alanineamino
      transferase (ALT), sodium, potassium and chloride. The onset of analgesia (mean
      +/- SEM) was faster in group C (3.2 +/- 0.20 min) compared with that of group B
      (4.6 +/- 0.22 min) and group A (34.0 +/- 1.86 min). Analgesia of the thorax,
      flank, inguinal region, hind limbs, perineum and tail was complete in group C,
      but mild to moderate in groups A and B. Ataxia was severe in group C and mild in
      groups A and B. Mild to deep sedation was produced by groups A and C animals.
      Group B animals failed to produce sedation. Longer duration and greater depth of
      analgesia was produced in animals of group C. Heart rate, respiratory rate and
      rectal temperature decreased in groups A and C. The haematological parameters
      decreased in all the groups. The biochemical parameters like glucose, cortisol,
      BUN, creatinine, and ALT increased in all the animals. However, total proteins
      and albumin decreased in the three groups. The plasma electrolytes sodium,
      potassium and chloride did not show any significant change. The results of this
      study indicated a possible synergistic analgesic interaction between epidurally
      administered xylazine and ketamine, without causing any marked systemic effects
      in water buffalo calves.

PMID- 16970634
TI  - Malignant schwannoma in an American buffalo (Bison bison bison).
AB  - A case of a malignant schwannoma in a 20-year-old male American buffalo (Bison
      bison bison) from the Grand Park Zoo, Gyeonggi Province, Republic of Korea is
      reported. The animal showed no apparent clinical signs before death except for
      wound on the neck. Grossly, neoplastic nodules of various sizes were observed on
      the skin, lung, heart, liver, stomach, mesentery and kidney. Histologically, the
      neoplastic nodules were composed of fusiform cells that formed multidirectional
      bundles. The tumour cells were arranged in interlacing bands and bundles. The
      nuclei were atypical, hyperchromatic, with blunt or round ends. In addition, few
      mitotic figures were observed in the skin, lung, heart, liver, stomach, intestine
      and kidney. Several immunohistochemical stains, e.g. vimentin, cytokeratin (CK),
      smooth muscle actin (SMA), S-100 and HMB45, were used in an attempt to
      differentially diagnose the tumour. The neoplastic cells tested positive to S
      100, but negative to vimentin, CK, SMA and HMB45. Based on the above findings,
      this case was diagnosed as a malignant schwannoma. To the best of our knowledge,
      this is the first report of a schwannoma in an American buffalo (B. b. bison).

PMID- 16970635
TI  - Gliomatosis cerebri in a dog.
AB  - Gliomatosis cerebri is a rare tumourous disease of the central nervous system
      consisting of glial cells characterized by diffuse widespread infiltration and
      preservation of preformed brain structures. This report describes a case of
      gliomatosis cerebri in a 9-year-old, male, flat-coated retriever dog with central
      nervous symptoms. Magnetic resonance imaging of the brain demonstrated ill
      defined hyperintense zones of paramedian white matter within the right cerebral
      hemisphere, brainstem and cerebellum. Histological examination showed a
      proliferation of tumour cells in the brain structures mentioned. Glial fibrillary
      acidic protein-immunohistochemistry revealed a lot of fibres positively stained.
      Based on these findings, the alteration was diagnosed as gliomatosis cerebri.

PMID- 16970636
TI  - Blood pressure level and outcomes in adults aged 65 and older with prior ischemic
      stroke.
AB  - OBJECTIVES: To examine the association between blood pressure (BP) levels and
      long-term stroke outcomes in elderly stroke survivors. DESIGN: Observational
      study. SETTING: The Cardiovascular Health Study (CHS) of 5,888 community-dwelling
      adults. PARTICIPANTS: Two hundred fifty-four adults aged 65 and older (mean age
      78.6) who sustained a nonfatal first ischemic stroke. MEASUREMENTS: BP levels
      assessed at prestroke and poststroke CHS visits were examined as predictors of
      stroke recurrence, coronary heart disease (CHD), combined vascular events (CVEs),
      and mortality. RESULTS: Higher poststroke BP level, assessed 261.6 days (mean)
      after stroke, was associated with higher risk of stroke recurrence over 5.4 years
      (mean) of follow-up. The multivariate-adjusted hazard ratio for stroke recurrence
      was 1.42 (95% confidence interval (CI) = 1.03-1.99) per standard deviation (SD)
      of systolic BP (P = .04) and 1.39 (95% CI = 1.01-1.91) per SD of diastolic BP (P
      = .04). Mortality was significantly greater in patients with low or high
      poststroke BP than in those with intermediate BP. Poststroke BP was not
      associated with risk of CHD or CVE, although further analyses suggested that high
      systolic BP predicted CHD and CVE in younger but not older subjects. Prestroke BP
      did not predict poststroke outcomes. CONCLUSION: In this observational study of
      adults aged 65 and older assessed approximately 8 months after stroke, low BP was
      associated with favorable risk of recurrent stroke, although high and low
      poststroke BP levels were associated with greater mortality. Long-term
      antihypertensive trials in older stroke survivors would increase knowledge about
      the benefits of lowering BP in this population.

PMID- 16970637
TI  - Metabolic syndrome and cardiovascular disease in older people: The cardiovascular
      health study.
AB  - OBJECTIVES: To assess the prospective association between metabolic syndrome
      (MetS) and cardiovascular disease (CVD) in older people and to evaluate the
      effect of lowering the threshold for impaired fasting glucose (IFG) on the
      prevalence of IFG and MetS and the risk of CVD. DESIGN: Prospective cohort study.
      SETTING: Four field centers in U.S. communities. PARTICIPANTS: Three thousand
      five hundred eighty-five subjects in the Cardiovascular Health Study free of
      diabetes mellitus and CVD at baseline (mean age 72, 62% female, 14% black).
      MEASUREMENTS: Baseline measures of MetS components and adjudicated incident CVD
      events. MetS (2001) was defined first using the original criteria from the Third
      Adult Treatment Panel Report of the National Cholesterol Education Program (> or
      =3 of the following: large waist circumference (women >88 cm, men >102 cm),
      elevated triglycerides (> or =1.70 mmol/L), low high-density lipoprotein
      cholesterol (men <1.04 mmol/L, women <1.30 mmol/L), elevated fasting glucose (6.1
      6.9 mmol/L), and high blood pressure (> or =130/85 mmHg or self-reported use of
      medications for hypertension). Subjects were also classified according to the
      revised definition of the MetS (2005) that applies the lower threshold for
      fasting glucose (5.6-6.9 mmol/L). RESULTS: During follow-up (median 11 years),
      818 coronary heart disease (CHD), 401 stroke, and 554 congestive heart failure
      (CHF) events occurred. Age- and race-adjusted hazard ratios (HRs) for CHD,
      stroke, and CHF were 1.30 (95% confidence interval (CI) = 1.07-1.57), 0.94 (95%
      CI = 0.73-1.21), and 1.40 (95% CI = 1.12-1.76) for women and 1.35 (95% CI = 1.10
      1.66), 1.51 (95% CI = 1.08-2.12), and 1.47 (95% CI = 1.14-1.90) for men,
      respectively. Overall, women and men with MetS (2005) were 20% to 30% more likely
      to experience any CVD event than subjects without MetS (2005). Using the lower
      cut-point for IFG resulted in a near tripling in IFG prevalence (16% to 46%) and
      an additional 9% classified with MetS (2005) but HRs similar to those estimated
      from the original MetS (2001) criteria. High blood pressure was the component
      most strongly associated with incident CHD. CONCLUSION: Results from this study
      of an elderly, population-based cohort provide support for earlier investigations
      in primarily middle-aged populations that link the presence of MetS with the
      development of CVD and further underscore the importance of recognizing and
      treating its individual components, particularly high blood pressure.

PMID- 16970638
TI  - The effect of urinary incontinence on quality of life in older nursing home
      residents.
AB  - OBJECTIVES: To determine whether nursing home residents with urinary incontinence
      (UI) have worse quality of life (QoL) than continent residents, whether the
      relationship between UI and QoL differs across strata of cognitive and functional
      impairment, and whether change in continence status is associated with change in
      QoL. DESIGN: Retrospective cohort study using a Minimum Data Set (MDS) database
      to determine cross-sectional and longitudinal (6 month) associations between UI
      and QoL. SETTING: All Medicare- or Medicaid-licensed nursing homes in Kansas,
      Maine, Mississippi, New York, and South Dakota during 1994 to 1996. PARTICIPANTS:
      All residents aged 65 and older, excluding persons unable to void or with
      potentially unstable continence or QoL status (recent nursing home admission,
      coexistent delirium, large change in functional status, comatose, near death).
      MEASUREMENTS: UI was defined as consistent leakage at least twice weekly over 3
      months and continence as consistent dryness over 3 months. QoL was measured using
      the validated MDS-derived Social Engagement Scale. RESULTS: Of 133,111 eligible
      residents, 90,538 had consistent continence status, 58,850 (65%) of whom were
      incontinent. UI was significantly associated with worse QoL in residents with
      moderate cognitive and functional impairment. New or worsening UI over 6 months
      was associated with worse QoL (odds ratio = 1.46, 95% confidence interval = 1.36
      1.57) and was second only to cognitive decline and functional decline in
      predicting worse QoL. CONCLUSION: This is the first study to quantitatively
      demonstrate that prevalent and new or worsening UI decreases QoL even in frail,
      functionally and cognitively impaired nursing home residents. These results
      provide a crucial incentive to improve continence care and quality in nursing
      homes and a rationale for targeting interventions to those residents most likely
      to benefit.

PMID- 16970639
TI  - Prevalence of tuberculous infection and active tuberculosis in old age homes in
      Hong Kong.
AB  - OBJECTIVES: To assess the prevalence of tuberculous infection and active
      tuberculosis (TB) in old age homes in Hong Kong and to determine whether there is
      institutional transmission in these homes. DESIGN: Cross-sectional. SETTING: Old
      age homes. PARTICIPANTS: Total of 2,243 residents, representing 84.6% of all
      residents in 15 old age homes; 1,698 were women, and 545 were men, with an
      average age of 82. MEASUREMENTS: All residents had a questionnaire-based
      interview, medical record review, two-stage tuberculin testing using two units
      purified protein derivative-RT23, and a chest x-ray. Those with radiological
      abnormalities had sputum examined for acid-fast bacilli. RESULTS: The estimated
      prevalence rate of active TB in this population was 669 per 100,000,
      significantly higher in men than in women (1,101 per 100,000 vs 530 per 100,000).
      The proportion with positive tuberculin reactivity (> or =10 mm induration) after
      two-stage testing was 68.6%, significantly higher in men than in women. There was
      no evidence of active transmission of disease in these old age homes, with
      restriction fragment length polymorphism (RFLP) analysis performed on five cases
      of active pulmonary TB in the home with the highest rate of TB showing unique
      RFLP patterns. CONCLUSION: The rate of active TB and TB infection in old age
      homes in Hong Kong is still high. Because treatment for latent TB carries a high
      risk for liver dysfunction in this population, clinicians and other healthcare
      workers need a high index of suspicion and to diagnose and treat this disease as
      early as possible to prevent transmission.

PMID- 16970640
TI  - A drink to healthy aging: The association between older women's use of alcohol
      and their health-related quality of life.
AB  - OBJECTIVES: To assess the relationship between alcohol intake and mortality in a
      cohort of women aged 70 and older and to explore the relationship between level
      of alcohol use and changes in physical and mental health-related quality of life.
      DESIGN: National longitudinal surveys from 1996 to 2002. SETTING: Community
      based. PARTICIPANTS: A national random sample of 12,432 Australian women aged 70
      to 75 at baseline. MEASUREMENTS: Alcohol consumption was the factor of interest,
      and the main outcome measures were survival and health-related quality of life,
      with adjustment for potential confounders. RESULTS: Women who did not consume
      alcohol or who drank rarely were more likely to die (nondrinkers' hazard (HR) =
      ratio 1.94, 95% confidence interval (CI) = 1.4-2.6; rare drinkers' HR = 1.58, 95%
      CI = 1.2-2.1) than women in the low-intake reference category (1-2 drinks per
      day, 3-6 days per week), or if they survived, they had lower health-related
      quality-of-life scores on the General Health and Physical Functioning subscales
      of the Medical Outcomes Study 36-item Short Form Survey after adjustment for
      smoking, comorbidity, education, body mass index, and area of residence.
      Nondrinkers also scored lower on the Mental Health and Social Functioning
      subscales. CONCLUSION: Being a nondrinker of alcohol was associated with greater
      risk of death and poorer health-related quality of life. Results for other levels
      of intake were consistent with current Australian alcohol consumption
      recommendations for women and indicated that moderate alcohol intake may carry
      some health benefits for older women in terms of survival and quality of life.

PMID- 16970641
TI  - Four components describe behavioral symptoms in 1,120 individuals with late-onset
      Alzheimer's disease.
AB  - OBJECTIVES: To investigate behavioral components of Alzheimer's disease (AD) and
      to analyze behavioral components in relation to disease severity, apolipoprotein
      E genotype (APOE), sex, years of education, age at onset, and cognitive
      impairment. DESIGN: Cross-sectional study. SETTING: Data were collected from
      community-dwelling individuals and those residing in nursing homes. PARTICIPANTS:
      A total of 1,120 individuals meeting National Institute of Neurological and
      Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders
      Association criteria for late-onset probable AD. MEASUREMENTS: Behavioral
      symptoms were assessed using the Neuropsychiatric Inventory. First-order
      polychoric correlations, controlling for disease severity, between the 12 symptom
      domain scores were estimated, and the resulting matrix underwent principal
      components analysis. RESULTS: Four interpretable components were identified:
      behavioral dyscontrol (euphoria, disinhibition, aberrant motor behavior, and
      sleep and appetite disturbances), psychosis (delusions and hallucinations), mood
      (depression, anxiety, and apathy), and agitation (aggression and irritability).
      Scores on the four components were associated with severity of cognitive
      impairment. Higher behavioral dysfunction, agitation, and mood component scores
      were associated with lower age at onset. Behavioral dysfunction and mood
      component scores were associated with sex. None of the components were associated
      with age at assessment, years of education, or number of APOE epsilon4 alleles.
      CONCLUSION: Four behavioral components were identified that were comparable with
      those observed previously. Future analysis of these components will strengthen
      understanding of the underlying pathology of behavioral symptoms and AD.

PMID- 16970642
TI  - Satisfaction with hospital at home care.
AB  - OBJECTIVES: To examine differences in satisfaction with acute care between
      patients who received treatment in a physician-led substitutive Hospital at Home
      program and those who received usual acute hospital care. DESIGN: Survey
      questionnaire of participants in prospective, nonrandomized clinical trial.
      SETTING: Three Medicare-managed care health systems and a Department of Veterans
      Affairs Medical Center. PARTICIPANTS: Two hundred fourteen community-dwelling
      elderly patients who required acute hospital admission for community-acquired
      pneumonia, exacerbation of chronic heart failure, exacerbation of chronic
      obstructive pulmonary disease, or cellulitis, 84 of whom were treated in Hospital
      at Home and 130 in the acute care hospital. INTERVENTION: Treatment in a Hospital
      at Home model of care that substitutes for treatment in an acute care hospital.
      MEASUREMENTS: A 40-question survey measuring nine domains of care for patients
      and a 37-question survey measuring eight domains of care for family members.
      RESULTS: A higher proportion of patients were satisfied with treatment in
      Hospital at Home than with the acute care hospital in eight of nine domains, and
      this difference was statistically different in four domains. Hospital at Home
      patients were more likely than acute hospital patients to be satisfied with their
      physician (adjusted odds ratio (AOR) = 3.84, 95% confidence interval (CI) = 1.32
      11.19), comfort and convenience of care (AOR = 6.52, 95% CI = 1.97-21.56),
      admission processes (AOR = 5.90, 95% CI = 2.21-5.76), and the overall care
      experience (AOR = 2.98, 95% CI = 1.08-8.21). Family members of patients treated
      in Hospital at Home were also more likely to be satisfied with multiple domains
      of care. CONCLUSION: Hospital at Home care was associated with greater
      satisfaction than acute hospital inpatient care for patients and their family
      members. These findings support further dissemination of the Hospital at Home
      care model.

PMID- 16970643
TI  - Day care service use is associated with lower mortality in community-dwelling
      frail older people.
AB  - OBJECTIVES: To clarify the association between day care service use and 21-month
      mortality in community-dwelling frail older people. DESIGN: Prospective cohort
      study (the Nagoya Longitudinal Study for Frail Elderly). SETTING: Community
      based. PARTICIPANTS: One thousand six hundred seventy-three community-dwelling
      older people (540 men, 1,133 women). MEASUREMENTS: Data included the clients'
      demographic characteristics; depression as assessed using the short version of
      the Geriatric Depression Scale; a rating for basic activities of daily living
      (ADLs); comorbidity; number of prescribed medications and physician-diagnosed
      chronic diseases; use of home-care services, including day care, visiting nurse,
      and home-help services; and number of regular medical checkups. Survival analysis
      of 21-month mortality was conducted using Kaplan-Meier curves and multivariate
      Cox proportional hazards models. RESULTS: Of the 1,673 participants, 726 were day
      care service users at baseline, and 268 (94 day care service users, 174 nonusers)
      died during the 21-month follow-up. Multivariate Cox regression models adjusting
      for potential confounders showed that day care service use was associated with
      reduction in mortality. Subgroup analysis demonstrated that day care service use
      was associated with less risk of mortality in subjects who were female; were in
      the youngest age group (65-74); had higher ADL scores, lower comorbidity,
      depression, no dementia; and used a visiting nurse service. Participants using
      day care service two and three times or more a week had 63% or 44% lower relative
      hazard ratios, respectively, than participants not using the service. CONCLUSION:
      Among community-dwelling frail older people, day care service use two or more
      times per week was associated with 44% to 63% lower 21-month mortality.

PMID- 16970644
TI  - Nursing home staff delivery of oral liquid nutritional supplements to residents
      at risk for unintentional weight loss.
AB  - OBJECTIVES: To describe nursing home (NH) staff delivery of oral liquid
      nutritional supplements to residents with an order to receive supplementation.
      DESIGN: Descriptive. SETTING: Six skilled NHs. PARTICIPANTS: One hundred thirty
      two long-stay residents. MEASUREMENTS: Research staff conducted direct
      observations for 2 days during and between meals and documented NH staff delivery
      of supplements, amount consumed (fluid ounces), and amount of assistance
      (minutes) provided by staff to encourage consumption. RESULTS: Eighty-eight
      percent had an order to receive a supplement one to three times daily (mode = 3);
      12% had an order to receive a supplement four to six times daily. Fewer than 10%
      received the supplement consistent with their orders during the 2 observation
      days. On average, NH staff provided a supplement less than once per participant
      per day during or between meals. When a supplement was provided, residents
      consumed an average+/-standard deviation of 4.91+/-2.19 fluid ounces during meals
      with 6.16+/-7.46 minutes of staff assistance and 3.98+/-2.60 fluid ounces between
      meals with less than 1 minute of staff assistance. Participants with orders that
      specified time of delivery received the supplement at a significantly higher
      frequency between meals. CONCLUSION: Oral liquid nutritional supplements are not
      provided consistent with orders in NH practice. Staff spends little time
      promoting supplement consumption during or between meals. The specificity of the
      order related to time of delivery may influence when and how often supplements
      are provided to residents.

PMID- 16970645
TI  - Postprandial hypotension in long-term care elderly patients on enteral feeding.
AB  - OBJECTIVES: To examine the prevalence and nature of postprandial hypotension
      (PPH) in orally fed (OF), nasogastric tube (NGT)-fed, and percutaneous endoscopic
      gastrostomy (PEG)-fed older people. DESIGN: Prospective comparative study.
      SETTING: Nursing and skilled nursing wards of three geriatrics hospitals.
      PARTICIPANTS: Three groups (OF, PEG, NGT) of long-term care patients (50 in each
      cohort) were enrolled. MEASUREMENTS: Blood pressure (BP) and heart rate
      measurements were obtained just before lunch and at 15-minute intervals for 90
      minutes after the completion of the meal. The meals were similar in caloric
      content and composition. RESULTS: PPH was evidenced in 64 (43%) patients. No
      significant intergroup (OF, PEG, NGT) differences were present. In 68% of PPH
      patients, the systolic BP (SBP) drop appeared within 30 minutes, and 70% reached
      their systolic nadir at 60 minutes. In 31%, the SBP drop was registered on only
      one measurement, whereas in 25%, the drop was detected on five to six
      measurements. All parameters were without notable intergroup differences.
      CONCLUSION: In enterally fed elderly patients (NGT or PEG), the rate and pattern
      of PPH are similar and not significantly different from that observed in OF
      patients.

PMID- 16970646
TI  - Energy-containing nutritional supplements can affect usual energy intake
      postsupplementation in institutionalized seniors with probable Alzheimer's
      disease.
AB  - OBJECTIVES: To determine whether increases in caloric intake associated with
      consumption of a mid-morning nutritional supplement for 3 weeks were maintained
      in the week after stopping the supplement and to investigate the effects of body
      mass index (BMI) and cognitive and behavioral measures on this response. DESIGN:
      Secondary analysis of a previously published randomized, crossover, nonblinded
      clinical trial. SETTING: A fully accredited geriatric care facility affiliated
      with the University of Toronto. PARTICIPANTS: Thirty institutionalized seniors
      with probable Alzheimer's disease (AD) who ate independently. MEASUREMENTS:
      Investigator-weighed food intake, body weight, cognitive (Severe Impairment
      Battery; Global Deterioration Scale) and behavioral (Neuropsychiatric Inventory-
      Nursing Home version; London Psychogeriatric Rating Scale) assessments. RESULTS:
      Individuals who responded successfully to supplementation as indicated by
      increases in daily energy intake were likely to maintain 58.8% of that increase
      postsupplementation, although stopping the supplement was associated with
      decreased habitual energy intake in low-BMI individuals who reduced their daily
      intakes during supplementation in response to the extra calories.
      Cognitive/behavioral tests were not reliable predictors of postsupplement intake.
      CONCLUSION: Institutionalized seniors with probable AD are likely to alter their
      usual energy intakes to maintain changes resulting from 3 weeks of
      supplementation. This effect may allow for rotating supplementation schedules in
      nursing homes that could reduce staff burden, but only for those individuals who
      are most likely to respond favorably. These data indicate that nutritional
      supplements and diet plans should be carefully prescribed in low-BMI individuals
      to limit variability in total energy provided and thus prevent lower-than-normal
      intake.

PMID- 16970647
TI  - High interest in screening and treatment for mild cognitive impairment in older
      adults: A pilot study.
AB  - OBJECTIVES: To assess interest of older adults in screening and treatment for
      mild cognitive impairment (MCI). DESIGN: Cross-sectional, in-person pilot survey
      with a convenience sample. SETTING: Two university-based geriatrics clinic
      waiting rooms in Chicago. PARTICIPANTS: Healthy adults aged 35 and older without
      cognitive impairment (n = 149). MEASUREMENTS: Following a description of MCI
      extracted from the Alzheimer's Association Website "Fact Sheet," questions
      concerning willingness to be screened and treated for MCI. RESULTS: Ninety-eight
      percent of respondents would be willing to be tested for MCI if a family member
      suggested they had memory problems, 99% were willing to take a medication if it
      would cut the risk of conversion from MCI to Alzheimer's disease (AD) in half,
      and 92% would take a medication to delay the conversion from MCI to AD by 1 year.
      If a family member suggested memory problems, African Americans were more willing
      than whites to be screened for MCI (75% vs 57%; P = .05). CONCLUSION: Older
      adults expressed high interest in screening and treatment for MCI. Interest in
      screening is even stronger in African Americans than in whites. Such high
      interest is potentially troubling, given the current state of knowledge about
      MCI.

PMID- 16970648
TI  - Deletion/insertion polymorphism of the angiotensin-converting enzyme gene and
      white matter hyperintensities in dementia: A pilot study.
AB  - OBJECTIVES: To examine the association between the angiotensin-converting enzyme
      (ACE) deletion/insertion (D/I) polymorphism and white matter hyperintensities
      (WMHs) in patients with dementia. DESIGN: Observational pilot study with
      adjustment for potential confounders using analysis of covariance. SETTING:
      Secondary care old-age psychiatry services in greater Manchester, United Kingdom.
      PARTICIPANTS: Ninety-seven patients with dementia: 49 with Alzheimer's disease
      (AD, National Institute of Neurological and Communicative Disorders and
      Stroke/Alzheimer's Disease and Related Disorders Association criteria) and 48
      with vascular dementia (VaD, National Institute of Neurological Disorders and
      Stroke/Association Internationale pour la Recherche et l'Enseignement en
      Neurosciences criteria). MEASUREMENTS: The ACE D/I polymorphism, WMHs (deep WMHs
      (DWMHs) and periventricular hyperintensities (PVHs)) on T2-weighted magnetic
      resonance imaging, and potential cardiovascular confounders. RESULTS: The D/D
      polymorphism of the ACE genotype was associated with severity of DWMH (P = .005)
      but not PVH (P = .34), corrected for age, cardiovascular risk factors, and type
      of dementia. Post hoc analyses were limited by statistical power but suggested an
      interaction with the apolipoprotein E epsilon4 allele. CONCLUSION: The results
      support previous observations that genetic factors influence the development of
      WMHs in dementia. The involvement of the ACE D/I polymorphism in the pathogenesis
      of DWMHs in dementia (AD and VaD), by a mechanism that is independent of its
      association with cardiovascular risk factors, should be confirmed in a large
      population-based sample.

PMID- 16970649
TI  - A randomized trial of olfactory stimulation using black pepper oil in older
      people with swallowing dysfunction.
AB  - OBJECTIVES: To determine the effect of olfactory stimulation with volatile black
      pepper oil (BPO) on risk factors for pneumonia. DESIGN: A 1-month randomized,
      controlled study. SETTING: Nursing homes in Japan that serve as long-term care
      facilities for older residents who are physically handicapped, mainly because of
      cerebrovascular disease. PARTICIPANTS: One hundred five poststroke residents.
      MEASUREMENTS: Latency of the swallowing reflex (LTSR), the number of swallowing
      movements, serum substance P (SP), and regional cerebral blood flow (rCBF).
      RESULTS: Nasal inhalation of BPO for 1 minute shortened LTSR, compared with that
      of lavender oil and distilled water (P < .03). Compared with the period before
      the study, the 1-month intervention using BPO improved LTSR with an increase of
      serum SP (P < .01). The number of swallowing movements for 1 minute during the
      nasal inhalation of BPO increased (P < .001). Multiple comparisons showed a
      poststudy increase in rCBF within the insular cortex (P < .001). Compared with
      the prestudy rCBF, BPO intervention increased rCBF in the right orbitofrontal and
      left insular cortex (P < .001). CONCLUSION: Inhalation of BPO, which can activate
      the insular or orbitofrontal cortex, resulting in improvement of the reflexive
      swallowing movement, might benefit older poststroke patients with dysphagia
      regardless of their level of consciousness or physical and mental status.

PMID- 16970650
TI  - Severe elder obesity and 1-year diminished lower extremity physical performance
      in homebound older adults.
AB  - OBJECTIVES: To determine whether severe obesity in older people is independently
      associated with diminished lower extremity physical performance (LEP) in a random
      sample of homebound older adults that were considered ambulatory. DESIGN:
      Prospective cohort with 1 year of follow-up (2000-02). SETTING: In-home
      assessments of homebound older adults in four North Carolina counties.
      PARTICIPANTS: Random sample of 282 home-delivered meal recipients aged 60 and
      older who completed both in-home assessments (n = 253) or were nursing home
      residents (n = 29) at the 1-year follow-up assessment of the Nutrition and
      Function Study. MEASUREMENTS: Objective measures were selected for baseline and 1
      year LEP (timed walking, static and dynamic balance, and chair rise) and baseline
      body mass index (BMI, based on measured weight and knee height). BMI was
      categorized as underweight/normal (<25.0 kg/m2), overweight (25.0-29.9 kg/m2),
      moderately obese (30.0-34.9 kg/m2), and severely obese (> or =35.0 kg/m2). Based
      on summary scores, overall LEP was categorized as poor, intermediate, or good.
      Sample characteristics included depressive symptomatology, fear of falling,
      medical conditions, and medication use. RESULTS: Almost 23% of participants were
      moderately obese and 15% severely obese. Only severe obesity independently
      increased the odds (odds ratio 2.9-7.0) for diminished performance at 1 year in
      individual tests and in overall LEP performance. Severe obesity was independently
      associated with poor LEP at both assessments or with decline in LEP at 1 year.
      CONCLUSION: These results highlight the need to distinguish between moderate and
      severe obesity in older people in terms of relationships with key functional
      outcomes. The findings identify severe obesity in older people as an important
      target for future interventions. In particular, this calls for greater
      understanding of intervention goals, whether to primarily target weight reduction
      or improvement in physical performance.

PMID- 16970651
TI  - Translating evidence-based falls prevention into clinical practice in nursing
      facilities: Results and lessons from a quality improvement collaborative.
AB  - OBJECTIVES: To describe the changes in process of care before and after an
      evidence-based fall reduction quality improvement collaborative in nursing
      facilities. DESIGN: Natural experiment with nonparticipating facilities serving
      as controls. SETTING: Community nursing homes. PARTICIPANTS: Thirty-six
      participating and 353 nonparticipating nursing facilities in North Carolina.
      INTERVENTION: Two in-person learning sessions, monthly teleconferences, and an e
      mail discussion list over 9 months. The change package emphasized screening,
      labeling, and risk-factor reduction. MEASUREMENTS: Compliance was measured using
      facility self-report and chart abstraction (n = 832) before and after the
      intervention. Fall rates as measured using the Minimum Data Set (MDS) were
      compared with those of nonparticipating facilities as an exploratory outcome.
      RESULTS: Self-reported compliance with screening, labeling, and risk-factor
      reduction approached 100%. Chart abstraction revealed only modest improvements in
      screening (51% to 68%, P < .05), risk-factor reduction (4% to 7%, P = .30), and
      medication assessment (2% to 6%, P = .34). There was a significant increase in
      vitamin D prescriptions (40% to 48%, P=.03) and decrease in sedative-hypnotics
      (19% to 12%, P = .04) but no change in benzodiazepine, neuroleptic, or calcium
      use. No significant changes in proportions of fallers or fall rates were observed
      according to chart abstraction (28.6% to 37.5%, P = .17), MDS (18.2% to 15.4%, P
      = .56), or self-report (6.1-5.6 falls/1,000 bed days, P = .31). CONCLUSION:
      Multiple-risk-factor reduction tasks are infrequently implemented, whereas
      screening tasks appear more easily modifiable in a real-world setting.
      Substantial differences between self-reported practice and medical record
      documentation require that additional data sources be used to assess the change
      in-care processes resulting from quality improvement programs. Interventions to
      improve interdisciplinary collaboration need to be developed.

PMID- 16970652
TI  - Dog ownership, walking behavior, and maintained mobility in late life.
AB  - OBJECTIVES: To examine dog walking among dog owners and the relationship between
      walking behavior of dog owners and non-dog owners and maintained gait speed over
      3 years. DESIGN: Cross-sectional and longitudinal analyses of a prospective
      cohort study. SETTING: Memphis, Tennessee, and Pittsburgh, Pennsylvania.
      PARTICIPANTS: Two thousand five hundred thirty-three community-dwelling adults
      aged 71 to 82 at 36 months of the Health, Aging and Body Composition Study.
      MEASUREMENTS: Dog ownership, reported walking behavior, change in walking
      behavior, and usual and rapid gait speed over 3 years. RESULTS: Of 394 dog
      owners, only 36% walked their dogs at least three times per week. Cross
      sectionally, dog walkers were more likely to achieve 150 minutes of walking per
      week and had faster usual and rapid walking speeds (1.20 vs 1.14 m/s and 1.62 vs
      1.52 m/s, respectively; P < .01 for both) than non-dog owners who did not walk at
      least three times per week and similar speeds as non-dog owners who walked at
      least 150 minutes per week (P > .50). Three years later, subjects who had been
      dog walkers at baseline were approximately twice as likely as any other group to
      achieve recommended walking levels, independent of covariates. Dog walkers
      experienced similar declines in usual and rapid walking speed as non-dog owners
      who walked at least three times per week but maintained their initial mobility
      advantage. CONCLUSION: Although dog ownership appears to facilitate walking
      behavior, only a minority of older dog owners walk their dogs. The mobility
      advantage of dog ownership was seen only in dog walkers and was similar to that
      associated with any walking. Given suboptimal walking activity in older adults,
      examining the degree to which dog ownership promotes walking activity in persons
      who do little walking on their own appears worth pursuing.

PMID- 16970653
TI  - Tobacco cessation counseling across the ages.
AB  - OBJECTIVES: To examine recent rates of tobacco cessation counseling and whether
      patient age or sex was associated with providers' adherence to tobacco cessation
      guidelines. DESIGN: Survey study. SETTING: The 2002 National Ambulatory Medical
      Care Survey (NAMCS). PARTICIPANTS: Analysis of 22,605 records representing 687
      million ambulatory care appointments with adults from the 2002 NAMCS.
      MEASUREMENTS: The proportion of visits by sex and age category during which
      physicians identified a patient's tobacco use status and counseled tobacco users
      to quit. RESULTS: The rates at which providers inquired about tobacco use were
      similar across groups, ranging from 65% of visits with men aged 20 to 44 to 73%
      of visits with women aged 45 to 59, but providers' rates of tobacco cessation
      counseling differed by age, ranging from 27% of visits with male tobacco users
      aged 45 to 59 to 6% of visits with male tobacco users aged 75 old and older.
      CONCLUSION: Although providers frequently ask their patients about tobacco use,
      they infrequently counsel patients to quit, especially if those patients are
      older men. Provider time constraints, misconceptions about older patients'
      ability and willingness to quit, or doubt about the potential health benefits of
      tobacco cessation in this age group may explain the lower counseling rates
      provided to older male patients. Because rates of counseling have declined in the
      last decade, providers should be reeducated about the need for and effectiveness
      of tobacco cessation counseling for men and women of all ages.

PMID- 16970654
TI  - Association between mild anemia and executive function impairment in community
      dwelling older women: The Women's Health and Aging Study II.
AB  - OBJECTIVES: To evaluate the relationship between mild anemia and executive
      function in community-dwelling older women. DESIGN: Cross-sectional. SETTING:
      Community-based. PARTICIPANTS: High-functioning subjects participating in the
      baseline assessment of the Women's Health and Aging Study (WHAS) II, Baltimore,
      Maryland, 1994 to 1996. WHAS II eligibility criteria included aged 70 to 80, a
      Mini-Mental State Examination score of 24 or greater, and absence of advanced
      disability (difficulty in no more than 1 domain of physical function). Included
      in this study were 364 subjects with a hemoglobin concentration 10 g/dL or
      greater and known executive function status. MEASUREMENTS: Trail Making Test
      (TMT) Parts B and A. Tertiles of time to complete each test were used to define
      best (bottom), intermediate, and worst (top) performance. Tertiles of the
      difference TMT-B minus TMT-A were calculated. Anemia defined as hemoglobin
      concentration less than 12 g/dL. RESULTS: The percentage of subjects in the worst
      TMT-B, TMT-A, and TMT-B minus TMT-A performance tertile was highest for those
      with anemia. Prevalent anemia substantially increased the likelihood of
      performing worst (as opposed to best) on the TMT-B (odds ratio (OR) = 5.2, 95%
      confidence interval (CI) = 1.3-20.5), TMT-A (OR = 4.8, 95% CI = 1.5-15.6), and
      TMT-B minus TMT-A (OR = 4.2, 95% CI = 1.0-17.2), even after controlling for age,
      education, race, prevalent diseases, and relevant physiological and functional
      parameters. CONCLUSION: This study provides preliminary evidence in support of
      the hypothesis that mild anemia might be an independent risk factor for executive
      function impairment in community-dwelling older adults. Whether such an
      association is causal or noncausal remains to be determined.

PMID- 16970655
TI  - Measuring physical and social environments in nursing homes for people with
      middle- to late-stage dementia.
AB  - OBJECTIVES: To evaluate measures of dementia care environments by comparing a
      special care facility (SCF) with traditional institutional facilities (TIFs).
      DESIGN: A cross-sectional comparative study of nursing home environments
      conducted as part of a longitudinal study on quality of life for residents with
      dementia. SETTING: Twenty-four traditional nursing homes and one special care
      facility. PARTICIPANTS: One SCF with six distinct environments, 24 TIFs with 45
      distinct environments, and 88 family members. MEASUREMENTS: Therapeutic
      Environment Screening Scale-2+ (TESS-2+); Special Care Unit Environmental Quality
      Scale (SCUEQS), a subset of the TESS-2+ items; Composite Above Average Quality
      Score (CAAQS), a composite score of all items on the TESS-2+; and Models of Care
      Instrument (MOCI). RESULTS: The SCUEQS did not detect a significant difference
      between the SCF and the TIFs (30.0 vs 27.2, P = .28). The CAAQS detected a
      significant difference between the SCF and the TIFs, whereby the SCF environments
      were rated as having above-average quality in 71.4% of the domains, compared with
      57.3% for the TIF environments (95% confidence interval (CI) for difference = 2.6
      25.6%, P = .02). Using the MOCI, SCF families were 1.8 times as likely to rate
      the SCF as a home or resort versus a hospital as TIF families rating TIFs (95% CI
      for odds ratio = 1.5-2.1, P < .001). CONCLUSION: The TESS-2+ CAAQS differentiated
      between physical environments better than the more established SCUQES. The MOCI
      distinguished between environments using a more holistic approach to measurement.
      The availability of environmental measures that are able to discriminate between
      specialized and traditional long-term care settings will facilitate future
      outcome-based research.

PMID- 16970656
TI  - Molecular medicine, the Medicare drug benefit, and the need for cost control.
AB  - The implementation of Medicare Part D, although successful in improving access to
      prescription drugs for millions of beneficiaries, will lead to a marked
      escalation in the cost of the Medicare program. An important component of the
      rise in costs will be specialty pharmaceuticals, including a group of drugs that
      are self-administered and that cost at least 1,000 dollars/month. The rate of
      growth in expenditures on specialty pharmaceuticals has been 34% per year.
      Although all these drugs confer benefits, the degree of benefit varies from
      dramatic (e.g., imatinib for chronic myelogenous leukemia) to cost-effective
      (e.g., tumor necrosis factor-alpha blockers for rheumatoid arthritis) to more
      modest (e.g., disease-modifying drugs used in multiple sclerosis). Historically,
      when costs within the Medicare program have risen, Congress has enacted price
      controls, as it did with hospitalization, physician services, and outpatient
      care. The Medicare Modernization Act (MMA) currently prohibits such an approach.
      Resorting instead to competition from generic drugs will be of little utility,
      because there is currently no mechanism to allow biogeneric drugs and patents in
      the biopharmaceutical industry to limit competition. Controlling the cost of the
      Medicare Part D program, as dramatically illustrated by the case of specialty
      pharmaceuticals, will require patent reform, giving the Food and Drug
      Administration jurisdiction over biogenerics, and amending the MMA to allow the
      Centers for Medicare and Medicaid Services to institute price controls.

PMID- 16970657
TI  - Development of a standardized patient instructor to teach functional assessment
      and communication skills to medical students and house officers.
AB  - Professional societies have called for increased geriatrics training for all
      medical students and physicians. A Geriatrics Standardized Patient Instructor
      (GSPI) was developed in which learners assess the functional status of a patient
      preparing for hospital discharge. Standardized patients (SPs) rate learners on
      functional assessment and communication skills, and provide feedback. Seventeen
      SPs were trained. Correlations of ratings by SPs with ratings by three
      geriatricians of videotaped encounters indicated good reliability (correlation
      coefficient = 0.69 and 0.70 for functional assessment and communication skills,
      respectively). Results from two learner groups illustrated the utility and
      feasibility of the GSPI. First, 138 house officers in nine specialties
      experienced the GSPI as a formative evaluation during implementation of new
      geriatrics curricula. Mean scores+/-standard deviation (on a 100-point scale) for
      functional assessment and communication skills were 78+/-16 and 86+/-11,
      respectively. House officers rated the overall experience positively (mean rating
      (1 = poor, 5 = excellent) 3.9+/-0.8). Second, 171 first-year medical students (M1
      s) encountered the GSPI as part of an intense, multimodal educational
      intervention. Mean scores on functional assessment and communication skills were
      93+/-10 and 93+/-7, respectively. Mean overall rating of the experience by M1 s
      was 4.1+/-0.8. After demonstrated success as a teaching tool in these two groups
      of learners, the GSPI has been successfully used with second- and third-year (M3)
      medical students and house officers from a total of 12 specialties and
      incorporated into multistation Objective Standardized Clinical Examination
      exercises for incoming house officers and M3 s. Unlike existing diagnosis
      oriented SPs, the GSPI can be used to assess and teach geriatrics skills to
      physician learners across disciplines and levels of training.

PMID- 16970658
TI  - Improving recruitment into geriatric medicine in Canada: Findings and
      recommendations from the geriatric recruitment issues study.
AB  - As the number of Canadians aged 65 and older continues to increase, declining
      recruitment into geriatric medicine (GM) raises concerns about the future
      viability of this medical subspecialty. To develop effective strategies to
      attract more GM trainees into the field, it is necessary to understand how
      medical students, residents, GM trainees, and specialists make career choices.
      The Geriatric Recruitment Issues Study (GRIST) was designed to assess specific
      methods that could be used to improve recruitment into geriatrics in Canada.
      Between November 2002 and January 2003, 530 participants were invited to complete
      the GRIST survey (117 Canadian geriatricians, 12 GM trainees, 96 internal
      medicine residents, and 305 senior medical students). Two hundred fifty-three
      surveys (47.7%) were completed and returned (from 54 participating geriatricians,
      9 GM trainees, 50 internal medicine residents, and 140 senior medical students).
      The survey asked respondents to rate factors influencing their choice of medical
      career, the attractiveness of GM, and the anticipated effectiveness of potential
      recruitment strategies. Although feedback varied across the four groups on these
      issues, consistencies were observed between medical students and residents and
      between GM trainees and geriatricians. All groups agreed that role modeling was
      effective and that summer student research programs were an ineffective
      recruitment strategy. Based on the GRIST findings, this article proposes six
      recommendations for improving recruitment into Canadian geriatric medicine
      training programs.

PMID- 16970659
TI  - Use of oral supplements in nursing homes: remaining questions.

PMID- 16970660
TI  - Paying with interest for a high interest in screening.

PMID- 16970661
TI  - Accidental ingestion of a press-through package: an underestimated cause of
      serious iatrogenic disease in the elderly?

PMID- 16970662
TI  - Paraneoplastic vasculitis and coexistent Trousseau's syndrome secondary to
      pancreatic carcinoma.

PMID- 16970663
TI  - Estimating glomerular filtration rate might help to avoid hypoglycemia.

PMID- 16970664
TI  - Demeaning the demented: Is "politically correct" getting old?

PMID- 16970665
TI  - Apolipoprotein e genotypes in nonagenarians.

PMID- 16970667
TI  - Prevalence of hyponatremia in elderly patients.

PMID- 16970668
TI  - Prevalence rates of mild cognitive impairment subtypes and progression to
      dementia.

PMID- 16970669
TI  - The relationship between hearing impairment and depression in older veterans.

PMID- 16970670
TI  - From urethra with shove: Bladder foreign bodies. A case report and review.

PMID- 16970671
TI  - Neurontin for Charles Bonnet Syndrome.

PMID- 16970675
TI  - Experimental autoimmune encephalomyelitis develops in CC chemokine receptor 7
      deficient mice with altered T-cell responses.
AB  - CC chemokine receptor 7 (CCR7) is involved in the initiation of immune responses
      by mediating the migration of naive T cells and mature dendritic cells to T-cell
      rich zones of secondary lymphoid organs where antigen presentation occurs. To
      address whether CCR7 plays a role in the development of autoimmunity, we induced
      experimental autoimmune encephalomyelitis in CCR7-deficient mice on a C57BL/6
      background (CCR7(-/-)) using the neuroantigen, myelin oligodendrocyte
      glycoprotein 35-55 amino acid peptide (MOG((35-55))) and Bordetella pertussis
      toxin (PTX). CCR7(-/-) mice acquired disease with an intensity similar to wild
      type littermates. MOG((35-55))-specific lymphocyte responses were dominant in the
      spleen of CCR7(-/-) mice, rather than in lymph nodes as observed in wild-type
      mice. These results indicate that effective immune responses (with altered
      kinetics) can develop in the absence of CCR7 but develop in the spleen rather
      than lymph nodes as CCR7 is necessary for T and dendritic cells to enter lymph
      nodes.

PMID- 16970676
TI  - Immunomodulation of Japanese encephalitis vaccine through CpG
      oligodeoxynucleotides in mice.
AB  - Synthetic oligodeoxynucleotides (ODN) containing unmethylated cytosine guanine
      (CpG) dinucleotides motifs act as immune adjuvant and provide means of modulation
      to immune responses when co-delivered with antigens. They stimulate both innate
      and adaptive immune responses and induce T helper 1 (Th1) immune responses. We
      investigated the immunomodulation of Japanese encephalitis (JE) vaccine using CpG
      ODN as an adjuvant. Mice were immunized with one dose of JE vaccine 0.1 ml with
      different concentrations (10, 25 and 100 microg) of CpG ODN. The serum antibody
      level and cytokines were evaluated and compared with mice immunized with two
      doses of JE vaccine alone. Our studies revealed that anti-JE antibody level in
      mice immunized with single dose of 0.1 ml JE vaccine and 100 microg CpG ODN were
      almost equal to mice immunized with two doses of JE vaccine alone. Furthermore,
      CpG ODN enhanced the production of TNF-alpha and Th1-mediated cytokines,
      including IFN-gamma and IL-2 compared with JE vaccine alone. In addition, absence
      of any significant changes in biochemical, haematological and histological
      studies suggest that CpG ODN are safe adjuvants for JE vaccine. Therefore, it is
      inferred that CpG ODN are effective and improve the efficacy of JE vaccine.

PMID- 16970677
TI  - Viable Mycoplasma mycoides ssp. mycoides small colony-mediated depression of the
      bovine cell responsiveness to the mitogen concanavalin A.
AB  - Mycoplasma mycoides ssp. mycoides biotype Small Colony (MmmSC) is the causative
      agent of contagious bovine pleuropneumonia (CBPP), which is still a major
      tropical cattle disease. Development of an efficient vaccine requires an
      understanding of the immunopathology of CBPP as MmmSC presents a strong ability
      to escape the host immune response. The objective of this study was to determine
      whether the presence of MmmSC can modulate the immune response induced by the
      mitogen Concanavalin A (ConA) on bovine immune cells [peripheral blood
      mononuclear cells (PBMC) and lymph node (LN) cells]. Comparative analysis of the
      immunomodulating properties of viable versus heat-killed MmmSC on ConA-stimulated
      immune cells revealed that while heat-killed MmmSC had no effect, viable MmmSC
      strongly depressed, in a concentration-dependent manner, the ConA mitogenic
      activity (blastogenesis and interferon-gamma production). Both B-cell and T-cell
      activation were affected with the highest impact on the CD4 T cells. The
      phenotypic analysis showed that the ConA-induced proliferation of CD25(+) cells
      was strongly reduced when co-exposed to viable MmmSC, confirming that events
      associated with ConA-induced cell activation were suppressed by the pathogen.
      This study thus demonstrated that viable MmmSC is able to inhibit the polyclonal
      mitogenic activity of the ConA on bovine PBMC and LN cells. This finding strongly
      suggests that the persistence of viable MmmSC may also thus inhibit the bovine
      immune response directed towards inactivated MmmSC, whether dead or in the form
      of antigens, also present during infection. This study confirmed that MmmSC has
      evolved an efficient mechanism to prevent its elimination from the host.

PMID- 16970678
TI  - Phagocytosis, production of nitric oxide and pro-inflammatory cytokines by
      macrophages in the presence of dematiaceous [correction of dematiaceus] fungi
      that cause chromoblastomycosis.
AB  - Chromoblastomycosis is characterized by the slow development of polymorphic skin
      lesions (nodules, verrucas, tumores, plaques and scar tissue). Inside the host,
      infectious propagules adhere to epithelial cells and differentiate into sclerotic
      forms, which effectively resist destruction by host effector cells and allow
      onset of chronic disease. A cellular immune response against fungi is essential
      to control infection. Amongst the cells of the immune system, macrophages play
      the most important role in controlling fungal growth. In this study, we show that
      the fungicidal characteristic of macrophages is dependent on the fungal species
      that causes chromoblastomycosis. We began by observing that the phagocytic index
      was higher for Fonsecaea pedrosoi and Rhinocladiella aquaspersa compared with
      that of other fungi. Complement-mediated phagocytosis was more important for
      Phialophora verrucosa and R. aquaspersa and was inhibited by mannan when F.
      pedrosoi and R. aquaspersa conidia were phagocytosed by macrophages. We showed
      that macrophages killed significantly only R. aquaspersa. We also found that the
      phagocytosis of fungi has functional consequences for macrophages as phagocytosis
      resulted in down-modulation of MHC-II and CD80 expression as well as in the
      inhibition of the basal liberation of NO. However, the inhibition of the basal
      liberation of NO nor the down-modulation of MHC and co-stimulatory molecules were
      observed in the presence of R. aquaspersa.

PMID- 16970679
TI  - Discrepancy in CD3-transmembrane peptide activity between in vitro and in vivo T
      cell inhibition.
AB  - Electrostatic amino acid interactions between receptor subunits within the T-cell
      antigen receptor (TCR) transmembrane domain are critical for the formation of the
      TCR-CD3 complex. Core peptide, a short peptide corresponding to the TCR-alpha
      transmembrane region, containing two positively charged amino acids, is known to
      inhibit T-cell function in vitro and in vivo. The aim of this study was to
      examine peptides corresponding to the syntactic transmembrane CD3 region binding
      to TCR-alpha for their ability to inhibit T-cell activation in vitro and in vivo.
      Three peptides matching the transmembrane sequence of CD3-delta, -epsilon and 
      gamma were synthesized and tested in different biological in vitro and in vivo
      systems for their effect on T-cell activity. The CD3-peptides had no impact on T
      cell function in vitro, but surprisingly, decreased signs of inflammation in the
      adjuvant arthritis rat model in vivo. Preliminary evidence suggests that peptides
      with CD3 transmembrane-derived sequences can inhibit an immune response as
      assessed by adjuvant-induced arthritis. The lack of in vitro activity may lead to
      a wasteful disregard of active compounds in the process of drug discovery and
      development.

PMID- 16970680
TI  - Application of chimerism-based drug-induced tolerance to rat into mouse
      xenotransplantation.
AB  - The current critical shortage of human donor organs has stimulated the
      feasibility of the xenogenic transplantation, such as swine to primate. We have
      previously reported the induction of donor-specific tolerance in MHC-disparated
      recipient mice by using our cyclophosphamide (CP)-induced tolerance conditioning.
      In this study, we examined the efficacy of our CP-induced tolerance conditioning
      in xenogenic transplantation model. F344 rats and B10 mice were used as donors
      and recipients. Recipient mice were treated with donor spleen cells, CP, Busulfan
      and bone marrow cells, with or without prior NK-cell depletion. Donor mixed
      chimerism, and the presence of donor reactive T-cell population were analysed by
      flow cytometry. The survival of the donor skin grafts were observed after the
      conditioning. Donor mixed chimerism was temporary induced but terminated at 10
      weeks after treatments. Donor-specific prolongation of the skin graft survival
      was observed after the treatments, however, grafts were rejected in the long
      term. NK-cell depletion, prior to the treatments, did not affect the levels of
      the mixed chimerism or graft prolongation. The donor-reactive recipient T-cell
      population was remained the same level as the untreated mice, suggesting the
      failure of the induction of the central T-cell tolerance. Thus, partial efficacy
      of our CP-induced tolerance treatments in the rat to mice xenotransplantation was
      observed. Our results suggested that the additional treatments were required to
      establish the stable xenogenic tolerance.

PMID- 16970681
TI  - Combined costimulation blockade prevents rejection of allogeneic islets in mice.
AB  - There is a need for immunosuppressive protocols in islet transplantation that are
      neither nephrotoxic nor diabetogenic. We have examined blockade of the CD28-B7,
      CD40-CD40L and ICAM-LFA-1 pathways in a model of allogeneic islet transplantation
      in mice to determine the efficacy of this blockade in prolongation of graft
      survival. Histological evidences of inflammation and function were evaluated in
      grafts that had been functioning for 100 days. Treatment with a combination of
      all three drugs, or with CTLA4Ig and anti-CD40L, administered four times during
      the first six postoperative days, resulted in an excellent graft survival. All
      animals had a graft survival of >100 days (i.e. indefinitely). Mice treated with
      CTLA4Ig and anti-CD40L all showed well-preserved islets without signs of
      degeneration or destruction. There were no signs of rejection, as evidenced by
      the absence of infiltrating lymphocytes. This group had the least amount of
      rejection/inflammation changes according to ranking of all grafts. In conclusion,
      a short induction treatment with anti-CD40L and CTLA4Ig totally prevents
      rejection and preserves the allogeneic islets transplanted to mice. The addition
      of anti-LFA-1 did not confer any benefit.

PMID- 16970682
TI  - Plasmacytoid dendritic cells induce a distinct cytokine pattern in virus-specific
      CD4+ memory T cells that is modulated by CpG oligodeoxynucleotides.
AB  - Inherent properties of dendritic cell (DC) subsets are important in the
      regulation of naive T-cell differentiation (e.g. Th1 versus Th2 cells), whereas
      effector memory T cells are believed to produce a fixed cytokine repertoire
      independent of the type of antigen presenting cell. Here we show that two
      distinct human DC subsets, plasmacytoid DC (PDC) and myeloid CD11c+ DC, induced
      autologous mumps virus-specific memory CD4(+) T cells to produce markedly
      different cytokine patterns upon antigen stimulation. PDC stimulated the T cells
      to produce gamma-interferon (IFN-gamma) and interleukin-(IL)-10, whereas CD11c+
      DC induced lower levels of IFN-gamma, virtually no IL-10, but significant levels
      of IL-5. Analysis of intracellular cytokine production showed simultaneous
      production of IL-10 and IFN-gamma in mumps-specific T cells activated by PDC, a
      cytokine pattern similar to that described for Th1-like regulatory cells.
      Introduction of CpG oligodeoxynucleotides in PDC/T-cell co-cultures had
      synergistic effect on virus-dependent IFN-gamma production, whereas the other
      cytokines remained unchanged. Together, our results show that the type of DC
      involved in reactivation of previously primed T cells may have significant impact
      on the resulting cytokine response and suggest that targeting of viral antigens
      and adjuvant to specific DC subsets should be considered in the design of
      therapeutic antiviral vaccines.

PMID- 16970683
TI  - Increased soluble 4-1BB ligand (4-1BBL) levels in peripheral blood of patients
      with multiple sclerosis.
AB  - 4-1BB ligand (4-1BBL; CD137L) is a member of the tumour necrosis factor
      superfamily expressed primarily on antigen presenting cells such as B cells,
      macrophages and dendritic cells. Its engagement with the receptor 4-1BB (CD137)
      has been shown to promote T-cell activation and regulate proliferation and
      survival of T cells. The role of the costimulatory molecule in multiple sclerosis
      (MS) remains unclear. In this study, the expression of 4-1BBL and soluble 4-1BBL
      (s4-1BBL) protein levels were analysed in peripheral blood of MS patients.
      Compared with healthy controls, MS patients had an increase in both plasma s4
      1BBL protein levels and expression of 4-1BBL in CD14(+) monocytes. In contrast,
      myelin basic protein-reactive T-cell proliferation was not found to be inhibited
      by the use of an anti-4-1BBL antibody. The elevated s4-1BBL protein levels in the
      MS patients may function as a self-regulatory mechanism of 4-1BB/4-1BBL
      interaction and costimulation.

PMID- 16970684
TI  - Increase in adhesion molecules in cerebrospinal fluid of children with mumps and
      mumps meningitis.
AB  - Adhesion molecules play a key role in leucocyte migration into the central
      nervous system (CNS). Concentrations of endothelial-derived soluble intercellular
      adhesion molecule-1 (sICAM-1) and leucocyte-originated soluble L-selectin (sL
      selectin) in cerebrospinal fluid (CSF) of children with mumps meningitis
      (mononuclear pleocytosis, n = 33) and mumps (absence of pleocytosis, n = 9) were
      compared with values from age-matched control group (n = 19). In 14 patients from
      the meningitis group, adhesion molecule levels together with albumin
      concentration were estimated in paired CSF/serum samples to calculate
      concentration quotients and determine molecule intrathecal release. Both sICAM-1
      (median 3.44 versus 0.86 ng/ml; P < 0.0001) and sL-selectin (median 29.91 versus
      8.52 ng/ml; P < 0.0001) concentrations in CSF were increased in mumps meningitis
      patients compared with controls. Increased levels of the selected adhesion
      molecules were also observed in mumps patients without CNS involvement when
      compared with controls (median sICAM-1: 1.14 versus 0.86 ng/ml, sL-selectin:
      13.54 versus 8.52 ng/ml; P < 0.01). Additionally, the concentration of adhesion
      molecules was found to correlate with CSF leucocyte count. Considerable
      correlation of sICAM-1 and sL-selectin quotients and corresponding albumin
      quotients suggests that a majority of the soluble adhesion molecules originated
      from the bloodstream. Analysis of adhesion molecule levels demonstrated indirect
      evidence of brain-derived fractions. Our results suggest the involvement of
      adhesion molecules during the early phase of mumps meningitis.

PMID- 16970685
TI  - Involvement of innate immunity in the pathogenesis of chronic hepatitis C in
      children.
AB  - The aim of the study was to assess the role of selected elements of innate
      immunity in the pathogenesis of chronic hepatitis C in children. The study
      comprised 20 children with chronic hepatitis C (group 1), nine healthy hepatitis
      C virus (HCV) seropositive children (group 2) and 18 healthy children (control
      group). We evaluated the expression of Toll-like receptor (TLR)2 and TLR4 on
      peripheral blood neutrophils, and generation of interleukin (IL)-8, IL-10, IL-12
      and reactive oxygen species (ROS) by neutrophils. The performed tests
      demonstrated higher expression of TLR2 and TLR4 on stimulated neutrophils and of
      TLR4 on non-stimulated neutrophils in group 1 in comparison to HCV seropositive
      children and controls. In group 1, the expression of TLR2 after granulocyte
      colony-stimulating factor (GCSF) stimulation showed positive correlation with
      alanine aminotransferase and asparate aminotransferase activities, while the
      expression of TLR2 without stimulation and of TLR4 after GCSF stimulation also
      correlated with necrosis. IL-12 generation by lipopolysachcharide-stimulated
      neutrophils was higher in group 1 versus controls. In group 1, maximum
      chemiluminescence (CL) without pre-activation, both spontaneous and after formyl
      methionyl-leucyl-phenylanine and phorbol-myristate-acetate (PMA) stimulation, was
      significantly lower than in the controls. CL after tumour necrosis factor-alpha
      pre-activation and PMA stimulation was still lower than in the controls, however,
      after opsonized zymosane stimulation it was significantly higher than in the
      controls. Our studies suggest the involvement of neutrophils in the pathogenesis
      of chronic hepatitis C in children. Neutrophils demonstrate increased expression
      of TLR2 and TLR4 (correlating with the features of hepatocytic damage and
      intensification of necrosis), inhibition of oxygen metabolism, and after TNF
      alpha pre-activation higher ability to produce ROS.

PMID- 16970686
TI  - Retrospective analysis of patients with lupus nephritis: data from a large
      clinical immunological center in Hungary.
AB  - The aim of this study was to review the development, histological type and
      outcome of 117 patients with lupus nephritis managed and followed by the Division
      of Clinical Immunology, 3rd Department of Internal Medicine, University of
      Debrecen, Debrecen, Hungary. The method used was a retrospective study in 117
      patients with lupus nephritis followed between 1974 and 2004. The average
      occurrence of lupus nephritis was 3 (women) and 4.4 (men) years later after the
      diagnosis of systemic lupus erythematosus, 43 (46.2%) patients had class IV lupus
      nephritis. The initial therapy was intravenous cyclophosphamide treatment for 6
      months in 37 (31.6%) patients. End-stage renal disease had developed in nine
      (7.6%) patients. The 5-year survival rate was 99.1%. Despite the well-known and
      proved risk factors like hypertension, high serum creatinine, renal failure at
      onset or membranous glomerulonephritis, the outcome of the disease in our patient
      population was more favourable than one would expect according to the data
      available in the literature. The authors would like to draw attention to the
      importance of systematic care of patients with systemic lupus erythematosus,
      which may lead to a better clinical outcome.

PMID- 16970687
TI  - A differential association of interferon-gamma high-producing allele T and low
      producing allele A (+874 A/T) with Hashimoto's thyroiditis and Graves' disease.
AB  - Cytokines play a crucial role in the pathogenesis of autoimmune thyroid disease.
      The aim of this study was to investigate the relationship of the single base
      change polymorphic variants identified in the first intron of interferon-gamma
      (IFN-gamma) (+874 T/A) with susceptibility to thyroid dysfunctions. A total of
      340 subjects were included in the study comprising of 190 patients (104 patients
      with Hashimoto's thyroiditis, 26 with non-Hashimoto's hypothyroidism and 60
      Graves' disease) and 150 controls. Genotyping was done by amplification
      refractory mutation system-polymerase chain reaction using a set of sequence
      specific primers. Statistical analysis revealed a significant association between
      high IFN-gamma-producing genotype TT and Hashimoto's thyroiditis compared to
      controls (P value < 0.001). On the other hand, the frequency of genotype TT was
      decreased in patients with Graves' hyperthyroidism with a significant increase in
      low IFN-gamma-producing genotype AA among this group (P = 0.03). To conclude the
      results of the study suggest a differential association of high- and low
      producing alleles of IFN-gamma gene with Hashimoto's thyroiditis and Graves'
      disease. The high IFN-gamma-producing allele T was observed to be associated with
      Hashimoto's thyroiditis in the present study where as in Graves' hyperthyroidism
      the association was observed to be stronger with the low producing allele A.

PMID- 16970688
TI  - Resistance against natural killer cell cytotoxicity: analysis of mechanisms.
AB  - Target cell resistance against natural killer (NK) cell-mediated cytotoxicity
      obstructs NK cell-based immunotherapy of leukaemia. Several mechanisms of
      resistance have been described. Because of lack of simple assays for analysing
      these mechanisms, their relative impact on a given effector-target pair is mostly
      unknown. We here analysed the combination of the Granzyme B (GrB) enzyme-linked
      immunospot assay (ELISPOT) for the assessment of NK cell reactivity and
      cytotoxicity assays to estimate target cell escape mechanisms. Target cell
      recognition failure leads to negative GrB ELISPOT results, whereas target cell
      resistance shows positive GrB ELISPOT results in the absence of cytotoxicity. We
      confronted NK cells with the sensitive target cell line K562, and with the
      resistant cell lines ML2, SupB15 and Raji. ML2 cells sufficiently activated GrB
      release whilst being resistant against cytotoxic granules of NK cells. Partial
      resistance of Raji results from the interaction of HLA class I with inhibitory
      killer immunglobulin-like receptors (KIR) on the NK cells. Failure of target
      recognition by HLA class I-KIR interaction, lacking ligands to stimulatory NK
      cell receptors and partial resistance to cytotoxic granules all contributed to
      resistance of SupB15. In conclusion, revealing the mechanisms of resistance
      against NK cell-mediated cytotoxicity may allow improving the results of NK-based
      immunotherapy.

PMID- 16970690
TI  - So you want to be a dermasurgeon: how to get training or choose a fellowship.
AB  - BACKGROUND There are many routes to obtaining training in dermasurgery. OBJECTIVE
      The objective is to discuss some considerations that may guide selection of
      dermasurgery training. METHODS Current training options are reviewed. RESULTS
      Some considerations that may guide selection of type of dermasurgery training
      include: (1) individual temperament; (2) the subtype of dermasurgery in which
      training is desired (Mohs, cosmetic surgery, laser); (3) family and geographic
      factors; (4) preference for private practice versus academic career; and (5)
      proportion of future practice to be devoted to dermasurgery. CONCLUSIONS There
      are a growing number of training choices for budding dermasurgeons, with multiple
      options available for each set of particular circumstances.

PMID- 16970689
TI  - Evaluation of recombinant serine-rich 45-kDa antigen (ML0411) for detection of
      antibodies in leprosy patients.
AB  - The potential of the recombinant serine-rich 45-kDa antigen (ML0411) of
      Mycobacterium leprae to aid in detecting M. leprae-specific serum antibodies was
      assessed by an enzyme-linked immunosorbent assay (ELISA) in leprosy patients and
      controls comprising of tuberculosis patients, other unrelated skin-diseased
      patients and healthy individuals from India. All 18 multibacillary (MB) and 18/38
      (47.4%) of the paucibacillary (PB) leprosy patients were found positive. None of
      the controls was positive, yielding complete (0/49) specificity in the series
      tested here. On the other hand, an anti-phenolic glycolipid-1 (PGL-I) antibody
      detecting assay yielded detectable responses in 94.4% (17/18) of MB and 36.8%
      (14/38) of PB leprosy patients. Only two of 49 (4.1%) controls were positive,
      giving a specificity of 95.9%. Further, there was a good concordance (agreement
      of 83.8%; chi(2) = 40.3, P < 0.001; kappa = 0.63) between the two assays. Thus,
      the 45-kDa-based assay was slightly better than anti-PGL-I antibody-detecting
      assay. Interestingly, when combining the results of both the assays together for
      all leprosy patients (MB + PB), the combined sensitivity was significantly higher
      than that of the anti-PGL-I antibody-detecting ELISA alone (73.2% versus 55.4%; P
      < 0.05), but not (P > 0.05) compared with the 45-kDa antigen-based assay alone.
      Similarly, in case of PB patients, using both assays in combination, the
      sensitivity was significantly higher compared with anti-PGL-I antibody-detecting
      assay alone (60.5% versus 36.8%; P < 0.05). While adopting the combinatorial
      approach, the specificity remained invariably high (>95%). In conclusion, the
      results of the present study indicate that the M. leprae 45-kDa protein is a
      potent B-cell antigen and may be a useful serodiagnostic reagent.

PMID- 16970691
TI  - Warm and neutral tumescent anesthetic solutions are essential factors for a less
      painful injection.
AB  - BACKGROUND: Tumescent local anesthesia is widely used in dermatologic surgery.
      Minimizing pain associated with injections is crucial to successful surgical
      procedures. OBJECTIVE: This study investigates the pain associated with warm and
      room temperatures in neutralized or nonneutralized tumescent anesthetic solutions
      injection. METHODS: Thirty-six patients with axilla osmidrosis who underwent
      local anesthesia for surgery were randomly assigned to three groups. Group A
      received warm neutral (40 degrees C) and room-temperature neutral (22 degrees C)
      tumescent injections to each axillary region. Group B received warm neutral (pH
      7.35) and warm nonneutral (pH 4.78) tumescent injections on each side of axilla.
      Group C received warm nonneutral and room-temperature nonneutral tumescent
      injections on each side of axilla. Pain associated with infiltration of
      anesthesia was rated on a visual analog scale (VAS). RESULTS: A statistically
      significant decrease (p < .001) in pain sensation was reported on the warm,
      neutral injection side (mean rating, 32.7 mm) compared with the room-temperature,
      neutral injection side (mean rating, 53.3 mm). Patient-reported pain intensity
      was significantly lower on the side that received warm, neutral tumescent
      anesthesia (mean rating, 26.8 mm) than on the side receiving warm, nonneutral
      tumescent anesthesia (mean rating, 44.9 mm; p < .001). The difference in VAS
      scores between warm neutral (mean rating, 23.9 mm) and room-temperature
      nonneutral (mean rating, 61.2 mm) was statistically significant (p < .001).
      CONCLUSION: The warm, neutral tumescent anesthetic preparation effectively
      suppressed patient pain during dermatologic surgical procedures.

PMID- 16970692
TI  - Breast reduction performed by liposuction.
AB  - BACKGROUND: Large breasts and their functional sequelae can be remedied via
      breast reduction. This procedure has undergone frequent modification to decrease
      complications inherent in the large flap-based procedures. Liposuction has fewer
      complications than traditional incisional approaches and less scarring.
      OBJECTIVE: It is our hope that dermatologic and plastic surgeons reevaluate the
      role of liposuction breast reduction based on our results and consider it as an
      alternative to incisional techniques. METHODS AND MATERIALS: Medical charts,
      photoimaging, and mammography were used to assess outcomes. Statistical data were
      calculated using the Fisher exact test (two-sided). RESULTS: Patients reported a
      satisfaction rate of 93%. Nipple elevation was measured to be at a mean of 2.57
      cm compared to preoperative values. Older patients (>60 years of age) were noted
      to have a significantly larger nipple elevation (3.16 cm vs. 1.79 cm). Changes in
      volume ranged between 695.57 and 712.71 mL per breast. Radiographic changes
      induced by liposuction were not statistically different from those found in
      traditional reduction techniques. Patients with a normal body mass index (BMI)
      were more likely to have a larger breast reduction compared via the dip test.
      CONCLUSIONS: This study illustrates the efficacy of liposuction-based breast
      reduction for the properly selected patient.

PMID- 16970693
TI  - Clinical trial of a novel filler material for soft tissue augmentation of the
      face containing synthetic calcium hydroxylapatite microspheres.
AB  - BACKGROUND: The ideal injectable filler should yield great, long-lasting results,
      be biocompatible, reliable, safe, easy to use, and inexpensive. Radiesse (Bioform
      Inc., Franksville, WI) is a synthetic calcium hydroxylaptic filler that has all
      of the above qualities. OBJECTIVE To evaluate the effectiveness of Radiese as an
      injectable filler. METHODS: Eighty-two patients who underwent facial soft tissue
      augmentation using Radiese from April 2003 to 2004 were enrolled in this study.
      Pre-filled sterile syringes were used to inject the material into the soft
      tissues of the face. At the 3 month and six month visits, the physicians and the
      patients were asked to evaluate the result. RESULTS: Eighty-two patients were
      injected with Radiesse. The most common area of injection was the melolabial
      folds. All patients were evaluated during the 3 month follow up visit. There was
      an overwhelmingly positive response to the look and feel of the implant,
      averaging 4.6 on a grading scale from 1 to 5, for the patients as well as the
      injecting physicians. Similar responses were found at the 6 month follow up
      visit. CONCLUSION: Preliminary data indicate that Radiesse is easy to use and
      effective with little or no associated morbidity.

PMID- 16970694
TI  - Use of nonthermal blue (405- to 420-nm) and near-infrared light (850- to 900-nm)
      dual-wavelength system in combination with glycolic acid peels and topical
      vitamin C for skin photorejuvenation.
AB  - BACKGROUND AND OBJECTIVES: A major cause of skin aging is a chronic
      microinflammation created by environmental conditions and ultraviolet exposures.
      The hand-free application on the skin of a new intense light combining a
      narrowband blue-light (405- to 420-nm) antiinflammatory emission and a near
      infrared (850- to 890-nm) emission inducing self-defense mechanisms provides a
      new component to photorejuvenation and antiaging treatment protocols. STUDY
      DESIGN: An innovative skin rejuvenation schedule is presented in this study. It
      includes skin exposure to the light, with concomitant glycolic peels and daily
      vitamin C cream regimen for group A and only topical vitamin C cream and glycolic
      peels for control group B. RESULTS: Results show a significant improvement on
      pore size, rhytids, and radiance in group A. Conversely no improvement is noticed
      in group B except for a brief increase of skin radiance. Mechanisms of action of
      that specific light source are discussed. CONCLUSION: The exposure to this device
      can clinically enhance conventional antiaging protocols in skin rejuvenation.

PMID- 16970695
TI  - Treatment of angiokeratoma of Fordyce with pulsed dye laser.
AB  - BACKGROUND: Angiokeratomas of Fordyce are typically asymptomatic vascular lesions
      characterized by blue-to-red papules with a scale surface, most often located on
      the scrotum. Although considered benign, the lesions may bleed, either
      spontaneously or secondary to rupture, leading to patient anxiety and social
      embarrassment. OBJECTIVE: The objective was to determine the safety and
      effectiveness of 585-nm pulsed dye laser for the treatment of angiokeratomas of
      Fordyce. METHODS: Twelve patients with Fitzpatrick skin type II to IV were
      treated for angiokeratomas of Fordyce with pulsed dye laser (5.5-8.0 J/cm(2)) in
      two to six sessions. Lesion clearance was evaluated by two specialists on the
      basis of digital photographs taken before the first treatment and 2 months after
      the last treatment. RESULTS: Seven patients had an excellent response (clearance
      rating 75%-100%) and five patients had a good response (clearance rating 50%
      75%). Transient purpura and pain were present in all patients. Bleeding during
      treatment occurred in five patients. There were no permanent side effects.
      CONCLUSION: Pulsed dye laser is effective and safe for the treatment of
      angiokeratoma of Fordyce, with minimum side effects, providing an additional
      nonablative therapeutic option.

PMID- 16970696
TI  - Long-pulsed Nd:YAG laser treatment of venous lakes: report of a series of 34
      cases.
AB  - BACKGROUND: Some venous lakes do not respond well to traditional vascular lasers.
      The Nd:YAG laser output at 1,064 nm is less well absorbed by hemoglobin but
      penetrates more deeply into tissue. OBJECTIVE: This study was undertaken to
      assess the effectiveness of the long-pulsed Nd:YAG on venous lakes. METHODS:
      Thirty-five consecutive adult patients presenting with a venous lake were
      studied. Four patients had failed to respond to polidocanol 1% sclerotherapy, and
      1 patient to pulsed dye laser. Long-pulsed Nd:YAG was administered via a water
      cooled tip. Either a 3-mm spot at 250 J/cm(2) and 55 ms or a 5-mm spot at 140 to
      180 J/cm(2) was used depending on the size of the lesion. Clinical end points
      were characterized by hardening of the lesion, central blackening, minimal
      whitening of the periphery, and in most cases, an audible popping sound.
      Responses were assessed visually in 50% of cases or by phone contact in the
      remaining 50% if the lesion had completely disappeared. One patient was lost to
      follow-up. RESULTS: After a single treatment, 94% cleared completely; incomplete
      clearance occurred in 6%. There were no reported complications. CONCLUSIONS: The
      long-pulsed Nd:YAG laser is highly effective treatment for venous lakes of the
      lip and cheeks.

PMID- 16970697
TI  - Pacemakers and implantable cardiac defibrillators in dermatologic surgery.
AB  - BACKGROUND: Electrosurgery used during dermatologic surgical procedures can cause
      malfunction of pacemakers and implantable cardiac defibrillators (ICDs),
      producing problems with rhythm detection, proper function, or alteration of the
      device. Well-documented safety data on electrosurgery in patients with cardiac
      devices are limited. At Mayo Clinic in Rochester, Minnesota, the Pacemaker Clinic
      manages all patients with pacemakers and ICDs undergoing dermatologic surgery.
      The preoperative and postoperative evaluations provide a unique opportunity to
      evaluate the safety of dermatologic surgery with electrosurgery in such patients.
      OBJECTIVES: The objective was to review the evaluation and management, by an
      experienced cardiology team, of patients with cardiac devices undergoing
      dermatologic surgery and to characterize perioperative complications. METHODS: A
      retrospective chart review of all patients identified with pacemakers or ICDs
      undergoing Mohs micrographic or dermatologic excisional surgery with
      electrosurgery at Mayo Clinic 2001 through 2004 were identified. Data were
      abstracted to identify any possible complications. RESULTS: The 173 patients with
      pacemakers and 13 with ICDs undergoing dermatologic surgery had no documented
      complications from electrosurgery. CONCLUSION: The lack of complications
      associated with pacemakers and ICDs with electrosurgery is reassuring. The
      authors support published recommendations about techniques and precautions to
      optimize safety during electrosurgery in patients with cardiac devices. The care
      of patients with ICDs in particular requires special consideration.

PMID- 16970698
TI  - Aggressive squamous carcinomas of the scalp.
AB  - BACKGROUND: Squamous cell carcinomas of the scalp sometimes exhibit unusually
      aggressive behavior. OBJECTIVE: To describe a series of 11 cases of
      extraordinarily aggressive squamous cell carcinomas of the scalp. METHODS: These
      cases were selected based on a number of criteria including their tendency to
      recur after Mohs surgery, their propensity to develop satellite lesions, their
      tendency to invade bone, and their tendency to metastasize to regional nodes and
      systemically. A chart review was performed for each patient. RESULTS: Five of 11
      patients have succumbed to their disease. Of note is that the patients all had
      significant long-standing alopecia or thinning of their hair with marked actinic
      damage. Initial biopsies of the tumors revealed them to be either moderate or
      well-differentiated. Four of 11 patients developed satellite lesions and
      experienced recurrences despite obtaining clear margins with Mohs micrographic
      surgery. CONCLUSION: Squamous cell carcinomas of the scalp may metastasize and
      cause death. Thus, early diagnosis and treatment of these neoplasms is mandatory.
      In the setting of satellitosis, it is believed that it is best to perform a wide
      excision with margin control followed by split-thickness grafting and
      postoperative irradiation. The employment of radiation therapy, however, should
      be done with appropriate caution owing to the significant risk of
      osteoradionecrosis.

PMID- 16970699
TI  - Split-thickness skin graft in nonhelical ear reconstruction.
AB  - Defects of the nonhelical ear after skin cancer extirpation can be challenging.
      When other reconstructive options are not optimal, split-thickness grafting is an
      easy and effective technique for successful aesthetic and functional restoration
      of the ear.

PMID- 16970700
TI  - Squamous cell carcinoma arising adjacent to a recurrent pilonidal disease.

PMID- 16970701
TI  - Blue-whitish veil-like structure as the primary dermoscopic feature of combined
      nevus.
AB  - The combined nevus is a clinical simulator of melanoma, and clinical examination
      alone can be inadequate to diagnose this melanocytic pigmented skin lesion.
      Dermoscopy is a useful tool to differentiate the features related to each type of
      nevus. We report two cases of combined nevi dermoscopically characterized by a
      diffuse blue-whitish pigmentation similar to the blue-whitish veil, suggesting
      the diagnosis of melanoma.

PMID- 16970702
TI  - Reconstruction of an alar rim defect.

PMID- 16970704
TI  - Osteomyelitis of the outer calvarial plate after dermatologic surgery: a case
      report and review of the literature.

PMID- 16970705
TI  - De novo malignant eccrine spiradenoma: a case report and review of the
      literature.

PMID- 16970706
TI  - Palliation of skeletal melanoma metastases with isolated limb perfusion
      chemotherapy.

PMID- 16970707
TI  - Nonsyndromic segmental multiple infundibulocystic basal cell carcinomas in an
      adolescent female.

PMID- 16970708
TI  - Management of cutaneous neoplasms invading the parotid gland.

PMID- 16970709
TI  - Safer and less unpleasant incision and drainage of epidermal inclusion cysts.

PMID- 16970710
TI  - A simple technique for unassisted split-thickness skin graft harvesting from the
      thigh.

PMID- 16970711
TI  - The clinical use of deoxycholate for lipomas and earwax.

PMID- 16970712
TI  - Evaluation of peripheral vascular endothelial function with a portable ultrasound
      device.
AB  - Endothelial function can be assessed noninvasively by imaging the brachial artery
      with ultrasound before and during reactive hyperemia. However, the standard
      ultrasound equipment typically used for this purpose is limited by size and
      expense of the machinery. In this study, we compared the ability of a portable
      ultrasound device to standard ultrasound equipment to visualize the brachial
      artery for purposes of assessing peripheral vascular endothelial function. The
      portable device provided comparable imaging of the brachial artery at rest and
      during hyperemia to that of standard ultrasound technology. These findings
      support the feasibility of noninvasive evaluation of peripheral endothelial
      function in the ambulatory setting.

PMID- 16970714
TI  - The impact of marathon running upon ventricular function as assessed by 2D,
      Doppler, and tissue-Doppler echocardiography.
AB  - The impact of prolonged exercise upon right ventricular (RV) function is poorly
      understood and to date no studies have utilized tissue-Doppler imaging (TDI).
      Thirty-five marathon runners (age range 18-50 years) volunteered for the study.
      Two-dimensional, pulsed Doppler, and TDI studies were performed one day before
      and immediately following race completion. Right and left ventricular (LV)
      longitudinal TDI myocardial velocities were acquired from the tricuspid annulus
      and mitral annulus, providing velocity data during systole (S'), early diastole
      (E'), and late diastole (A'). Transtricuspid and transmitral, early diastolic
      (E), and late diastolic (A) velocities and ratios were assessed using
      conventional pulsed-wave Doppler. RV and LV fractional area changes (FAC) were
      calculated from RV and LV end-diastolic and end-systolic areas recorded from 2D
      scans in a subsample (n = 23). RV myocardial velocities were unchanged pre-post
      race in S' (21.1 +/- 2.7 to 21.7 +/- 4.5 cm s(-1), P > 0.05), reduced in E' (23.3
      +/- 3.5 to 19.9 +/- 5.3 cm s(-1), P < 0.05), increased in A' (19.1 +/- 3.6 to
      23.7 +/- 6.8 cm s(-1), P < 0.05) with a resultant decline in E'/A' (1.28 +/- 0.36
      to 0.94 +/- 0.45, P < 0.05). This pattern of data was mirrored in the LV.
      Similarly both pulsed-Doppler tricuspid and mitral E/A ratios decreased from pre-
      to postrace (P < 0.05). FAC for the RV and LV were unaltered postrace (P > 0.05).
      The impact of differing age, finishing time (173-330 min), hemodynamic loading
      and heart rate upon RV and LV function pre- to postrace was negligible. In
      conclusion, TDI and 2D data, for both the RV and LV demonstrated little change in
      systolic function after a marathon race. Conversely, a reduction in diastolic
      function was observed in both ventricles for which a mechanism has yet to be
      deduced.

PMID- 16970713
TI  - Accuracy of tissue Doppler echocardiography in the diagnosis of new-onset
      congestive heart failure in patients with levels of B-type natriuretic peptide in
      the midrange and normal left ventricular ejection fraction.
AB  - BACKGROUND: Based on the hypothesis that it reflects left ventricular (LV)
      diastolic pressures, B-type natriuretic peptide (BNP) is largely utilized as
      first-line diagnostic complement in the emergency diagnosis of congestive heart
      failure (HF). The incremental diagnostic value of tissue Doppler
      echocardiography, a reliable noninvasive estimate of LV filling pressures, has
      been reported in patients with preserved LV ejection fraction and discrepancy
      between BNP levels and the clinical judgment, however, its clinical validity in
      such patients in the presence of BNP concentrations in the midrange, which may
      reflect intermediate, nondiagnostic levels of LV filling pressures, is unknown.
      METHODS: 34 patients without history of HF, presenting with acute dyspnea at
      rest, BNP levels of 100-400 pg/ml and normal LV ejection fraction were
      prospectively enrolled (17 with congestive HF and 17 with noncardiac cause).
      Tissue Doppler echocardiography was performed within 3 hours after admission.
      RESULTS: Unlike BNP (P = 0.78), Boston criteria (P = 0.0129), radiographic
      pulmonary edema (P = 0.0036) and average E/Ea ratio (P = 0.0032) were predictive
      of congestive HF by logistic regression analysis. In this clinical setting,
      radiographic pulmonary edema had a positive predictive value of 80% in the
      diagnosis of congestive HF. In patients without evidence of radiographic
      pulmonary edema, average E/Ea > 10 was a powerful predictor of congestive HF
      (area under the ROC curve of 0.886, P < 0.001, sensitivity 100% and specificity
      78.6%). CONCLUSION: By better reflecting LV filling pressures, bedside tissue
      Doppler echocardiography accurately differentiates congestive HF from noncardiac
      cause in dyspneic patients with intermediate, nondiagnostic BNP levels and normal
      LV ejection fraction.

PMID- 16970715
TI  - Role of contrast-enhanced dobutamine stress echocardiography in predicting
      outcome in patients with known or suspected coronary artery disease.
AB  - Although the application of intravenous contrast agents during stress
      echocardiography has been shown to improve diagnostic accuracy for detecting
      coronary artery disease, less information exists regarding its prognostic value.
      The aim of this study was to determine the role of contrast-enhanced dobutamine
      stress echocardiography (DSE) for predicting future cardiac events in patients
      with coronary artery disease (CAD). We studied 893 patients (mean age: 66, 581
      men) with known or suspected CAD undergoing contrast-enhanced DSE. Positivity was
      defined as new/worsened wall motion abnormality or fixed abnormality during
      stress. All patients were followed for 15 +/- 10 months to evaluate hard cardiac
      events (cardiac death and nonfatal myocardial infarction) and total cardiac
      events (hard cardiac events, congestive heart failure, unstable angina, and late
      revascularization). Three patients were lost to follow-up, and 128 patients
      developed cardiac events, including 21 hard cardiac events. The 3-year event free
      survival rate was significantly lower in patients with positive DSE results than
      in those with negative DSE results. Stepwise Cox multivariate analysis revealed
      that positivity of DSE (P < 0.0001, Hazard ratio (HR): 2.48) and peak wall motion
      score index (WMSI) >1.5 (P < 0.0001, HR: 2.41) were independent predictors for
      total cardiac events. Considering hard cardiac events, the independent predictors
      were peak WMSI > 1.5 (P < 0.0001, HR: 6.65) and age > 70 years (P < 0.005, HR:
      3.27). We conclude that contrast-enhanced DSE provides important prognostic
      information for future cardiac events.

PMID- 16970716
TI  - Determinants of ischemic mitral regurgitation in patients with chronic anterior
      wall myocardial infarction: a real time three-dimensional echocardiography study.
AB  - OBJECTIVE: We sought to elucidate the geometric determinants of ischemic mitral
      regurgitation (IMR) in patients with chronic anterior myocardial infarction (MI).
      MATERIALS AND METHODS: In 16 patients with anterior MI only (Group A) and 18
      patients with both anterior and inferoposterior MI (Group B), three parallel
      equidistant anteroposterior (AP) planes (medial, central, lateral) perpendicular
      to the mitral valvular commissure-commissure plane were generated. The systolic
      tenting area of the mitral valve (MVTa) and the angles between the annular plane
      and leaflets (anterior, Aalpha; posterior, Palpha) on the AP planes were
      measured. The left ventricular end-systolic and end-diastolic volumes, and end
      diastolic and end-systolic mitral annular area (MAAs) were obtained. RESULT: The
      regurgitant orifice area (ROA) was significantly smaller in Group A than Group B
      (0.08 +/- 0.09 vs 0.20 +/- 0.18 cm(2), P < 0.05). In the total of 34 patients,
      the medial MVTa (P < 0.001), MAAs (P < 0.05) and the spherical index (P < 0.05)
      were three independent determinants of ROA while the left ventricular volumes
      were not. MAAs was the only independent determinant of ROA in Group A, while the
      medial MVTa was in Group B. Palpha (P < 0.05) and MVTa (P = 0.06) tended to be
      larger in the medial than the lateral side in Group B, while no differences were
      found in Group A. CONCLUSION: The geometry of the mitral valve apparatus was more
      important than the left ventricular volumes in determining the severity of IMR in
      patients with anterior MI. The posteromedial side tenting could play a critical
      role in causing significant IMR when the inferoposterior MI coexists with
      anterior MI.

PMID- 16970717
TI  - Automated three-dimensional analysis of mitral annular dynamics in patients with
      myocardial infarction using automated mitral annular tracking method.
AB  - BACKGROUND: A newly developed automated mitral annular tracking method (AMAT) has
      recently become available and enables us to perform automated analysis of mitral
      annular dynamics. PURPOSE: To evaluate mitral annular dynamics using AMAT.
      METHODS: AMAT was performed using a Toshiba Aplio SSA-770 ultrasound system in 15
      normal healthy volunteers (group N), 16 patients with anterior MI (group A), and
      12 inferior MI (group B). The distance between an annular point at end-diastole
      and at end-systole (distance D) was automatically measured using AMAT at the
      basal portion of the anterior, lateral, posterior, inferior, and inferoseptal
      wall. The angle between the mitral annular plane at end-diastole and the
      direction of movement of each mitral annular point from end-diastole to end
      systole (angle A) was also automatically measured at all five mitral annular
      points. The coefficients of variation (CV) of both distance D and of angle A were
      calculated as indices of asynchrony of mitral annular dynamics. RESULTS: CV of
      distance D in group A (22 +/- 9% (P < 0.01 vs group N)) and group B (22 +/- 10%
      (P < 0.01 vs group N)) were both significantly larger than in group N (13 +/-
      4%). CV of angle A in group A (15 +/- 10% (P < 0.05 vs group N)) and group B (15
      +/- 10% (P < 0.05 vs group N)) were also significantly larger than that in group
      N (8 +/- 3%). CONCLUSION: Automated analysis using AMAT showed that mitral
      annular dynamics of patients with MI were less symmetrical than in normal healthy
      volunteers.

PMID- 16970718
TI  - Quantitation of right ventricular volumes and ejection fraction by three
      dimensional echocardiography in patients: comparison with magnetic resonance
      imaging and radionuclide ventriculography.
AB  - Three-dimensional echocardiography (3DE) provides volumetric measurements without
      geometric assumptions. Volume-rendered 3DE has been shown to be accurate for the
      measurement of right ventricular (RV) volumes in vitro and in animal studies;
      however, few data are available regarding its accuracy in patients. This study
      examined the accuracy of 3DE for quantitation of RV volumes and ejection fraction
      (EF) in patients, compared to magnetic resonance imaging (MRI) and radionuclide
      ventriculography (RNV). Twenty patients underwent MRI, gated equilibrium RNV, and
      3DE using rotational acquisition from both the transesophageal and transthoracic
      approaches. RV volumes and EF were calculated from the 3DE data using multislice
      analysis (true Simpson's rule). RV volumes calculated by MRI (end-diastolic
      volume (EDV) 109.4 +/- 34.3 mls, end-systolic volume (ESV) 59.6 +/- 31.0 mls, and
      EF 47.7 +/- 17.1%) agreed closely with 3DE. For transesophageal echocardiography,
      EDV was 108.1 +/- 29.7 mls (r = 0.86, mean difference 1.3 +/- 17.8 mls); ESV was
      62.5 +/- 23.8 mls (r = 0.85, mean difference 2.8 +/- 15.1 mls); and EF was 43.2
      +/- 11.7% (r = 0.84, mean difference 4.5 +/- 9.7%). For transthoracic
      echocardiography, EDV was 107.7 +/- 27.5 mls (r = 0.85, mean difference 1.6 +/-
      18.2 mls); ESV was 59.7 +/- 22.1 mls (r = 0.93, mean difference 3.2 +/- 19.6
      mls); and EF was 45.2 +/- 11.5% (r = 0.86, mean difference 2.0 +/- 9.4%). There
      were close correlations, small mean differences and narrow limits of agreement
      between RNV-derived EF (43.4 +/- 12.1%) and both transesophageal (r = 0.95 mean
      difference 0.2 +/- 3.7%) and transthoracic 3DE (r = 0.95, mean difference 1.8 +/-
      5.4%). Three-dimensional echocardiography is a promising new method of
      calculating RV volumes and EF, comparing well with MRI and RNV. The accuracy of
      transthoracic 3DE was comparable to that of the transesophageal approach. Three
      dimensional echocardiography has the potential to be useful in the clinical
      assessment of RV disorders.

PMID- 16970719
TI  - Pulmonary vein edema in a patient undergoing coronary artery bypass graft surgery
      and concomitant radiofrequency ablation for chronic atrial fibrillation.
AB  - The syndrome of pulmonary vein stenosis characterized by pulmonary hypertension,
      dyspnea on exertion, and right heart failure, is a well-described complication of
      percutaneous ablation approaches, but has not been described with surgical
      approaches. We describe the case of a patient who developed localized edema at
      the pulmonary vein-left atrial junction after undergoing intraoperative
      radiofrequency ablation for chronic atrial fibrillation as part of CABG for
      severe triple vessel disease. The pulmonary vein edema resolved within 10 months
      suggesting that it may be a clinically silent and self-resolving phenomenon.

PMID- 16970720
TI  - An unusual cause of pulmonary vein stenosis: a case report and review of the
      literature.
AB  - We describe the case of a patient with the Carney syndrome and several resections
      for recurrent left atrial myxomas who underwent autotransplantation of the heart
      with resection of the left and right atria and reconstruction of both atria with
      bovine pericardium. She subsequently presented with severe shortness of breath,
      ascites, and peripheral edema. She was found to have stenosis of all four
      pulmonary veins and severe pulmonary hypertension. We describe the
      echocardiographic findings and review the literature on assessment of acquired
      pulmonary vein stenosis.

PMID- 16970721
TI  - Evaluation of cardiac involvement in hypereosinophilic syndrome: complementary
      roles of transthoracic, transesophageal, and contrast echocardiography.
AB  - Hypereosinophilic syndrome is a rare but important systemic disease with multiple
      clinical presentations. Approximately 40% of these cases have cardiac
      involvement. Echocardiography is the most easily available and versatile imaging
      modality in assessing cardiac involvement in this disease process. As described
      and reviewed in this case, it may be the first imaging modality to raise
      suspicion of this disease entity. Hence, clinicians interpreting echocardiograms
      and caring for patients need to be aware of the manifestations and complementary
      roles of various echo techniques in delineating cardiac involvement. Furthermore,
      the importance of a thorough history and laboratory review prior to
      echocardiography may provide valuable clues which may otherwise be missed.

PMID- 16970722
TI  - Tricuspid valve malfunction and ventricular pacemaker lead: case report and
      review of the literature.
AB  - Pacemaker implantation can be associated with several complications, including
      myocardial perforation with or without pericardial effusion, venous thrombosis,
      vegetations of the tricuspid valve (TV) or pacing lead, and tricuspid
      regurgitation (TR). The TR is thought to be derived from deformity or perforation
      of the TV by the pacing lead or secondary to atrioventricular discordance with
      asynchronous ventricular pacing. Severe TR can be deleterious to the patient
      because it raises the central venous pressure by increasing the right sided
      preload. Chronically, the increase in right sided blood volume can result in an
      increase in the right atrial pressure leading to a decrease in venous return and
      low cardiac output. Severe TR from leaflet adhesion to the pacemaker lead has not
      been reported before. With the aging of the population and the expanding use of
      pacemakers and implantable cardioverter defibrillators (ICD) in clinical
      practice, this complication may be seen more frequently. We present a patient
      diagnosed with severe TR, years after his pacemaker implantation. His TR was
      thought to be caused by adhesion of the tricuspid valve to his pacemaker lead.

PMID- 16970723
TI  - Mediastinal pancreatic pseudocyst diagnosed by transthoracic echocardiography.

PMID- 16970724
TI  - An asymptomatic case with single atrium.
AB  - Single atrium or common atrium is a rare, isolated defect. We report here an
      adult patient with single atrium detected by transthoracic echocardiography.

PMID- 16970725
TI  - Live/real time three-dimensional echocardiographic demonstration of left
      ventricular noncompaction and thrombi.
AB  - We describe two adult patients with left ventricular noncompaction in whom
      live/real time three-dimensional transthoracic echocardiography (3DTTE)
      supplemented two-dimensional transthoracic echocardiography in making a
      definitive diagnosis of clots coexisting with trabeculations in the left
      ventricle. Mobility of clots and the presence of central echolucencies consistent
      with clot lysis were best demonstrated by 3DTTE and served to confidently
      differentiate clots from adjacent trabeculations.

PMID- 16970726
TI  - Extensive cardiac lymphomatous infiltration manifesting as pericarditis and right
      ventricular outflow obstruction in a patient with multiorgan transplants.

PMID- 16970727
TI  - Color tissue Doppler to appropriately select a candidate for cardiac
      resynchronization therapy and test the procedure efficacy.

PMID- 16970728
TI  - A case of "unexplained" decompression sickness in a commercial diver.

PMID- 16970729
TI  - The cardiovascular effects of arteriovenous fistulas in chronic kidney disease: a
      cause for concern?
AB  - Arteriovenous fistulas (AVFs) are the preferred type of vascular access, but
      relatively little is known regarding their effects on cardiovascular remodeling
      and cardiac function. The following is a review regarding the immediate and long
      term complications associated with AVF creation, including the development of
      left ventricular hypertrophy, high-output cardiac failure, exacerbation of
      coronary ischemia, and the possible contribution to the development of central
      vein stenosis.

PMID- 16970730
TI  - Pulmonary hypertension in hemodialysis patients: an unrecognized threat.
AB  - Pulmonary hypertension (PH) is a progressive, fatal pulmonary circulatory disease
      that accompanies many conditions (including left to right side shunt) with
      compensatory elevated cardiac output. PH also complicates chronic hemodialysis
      (HD) therapy immediately after the creation of an arteriovenous (AV) access, even
      before starting HD therapy. It tends to regress after temporary AV access closure
      and after successful kidney transplantation. Affected patients have significantly
      higher cardiac output. This syndrome is associated with a statistically
      significant survival disadvantage. The laboratory hallmark of this syndrome is
      reduced basal and stimulatory nitric oxide (NO) levels. It appears that patients
      with end-stage renal disease (ESRD) acquire endothelial dysfunction that reduces
      the ability of their pulmonary vessels to accommodate the AV access-mediated
      elevated cardiac output, exacerbating the PH. Doppler echocardiographic screening
      of ESRD patients scheduled for HD therapy for the occurrence of PH is indicated.
      Early diagnosis enables timely intervention, currently limited to changing
      dialysis modality or referring for kidney transplantation.

PMID- 16970731
TI  - Three controversial issues in extracorporeal toxin removal.
AB  - The optimal method of extracorporeal removal of many toxic compounds is often a
      matter of debate. Due to the lack of well-designed studies, we are often left
      with circumstantial evidence, and we must exercise our best clinical judgment as
      to whether extracorporeal drug removal is beneficial and if so, by what method.
      It is clear, however, that rapidity in toxin removal is beneficial. We present
      three issues dealing with extracorporeal removal of toxins for which there is no
      definitive answer but which may arise in clinical practice. The first is whether
      continuous renal replacement therapy (CRRT) is better at removing dialyzable
      toxins than classic hemodialysis. The second is whether charcoal hemoperfusion is
      at all useful in treating paraquat poisoning. Finally, is any modality of
      extracorporeal treatment useful in the treatment of amatoxin poisoning? After a
      thorough literature review, it is evident that definitive answers are not
      strikingly apparent. However, extracorporeal treatment in the latter two
      instances may have potential benefit and may be the only hope for patient
      survival. Due to the urgent nature of treatment for poisoning, as well as the
      somewhat obscure nature of these issues, there may never be well-designed
      evidence-based studies to help guide us. In the meantime, we must continue to use
      less than ideal evidence and our own experience in dealing with these
      controversial issues to guide our decision-making process.

PMID- 16970733
TI  - How can erythropoietin requirements be reduced in dialysis patients?

PMID- 16970737
TI  - Altered laboratory findings associated with end-stage renal disease.
AB  - Several laboratory parameters can be altered in advanced renal failure. Results
      may be difficult to interpret and may become misleading and unreliable in such a
      context. On the other hand, some of the alterations may reflect real
      abnormalities. Thus sufficient knowledge and careful judgment are required by the
      clinician. We reviewed different publications related to biochemical anomalies in
      renal failure and report some of the main findings. The sections are divided as
      follows: cardiovascular risk factors and markers, inflammation markers,
      pancreatic and liver function tests, hormones, bone turnover indices and
      parathyroid hormone assays, tumor markers, carbohydrate metabolism indicators,
      and others. The information provided should be useful to clinicians involved in
      the care of renal failure patients.

PMID- 16970739
TI  - Management of lipid abnormalities associated with end-stage renal disease.
AB  - The management of lipid abnormalities in patients with end-stage renal disease
      (ESRD) remains controversial. Large, well-designed studies investigating the
      effects of dyslipidemia on cardiovascular (CV) morbidity and mortality and the
      role of cholesterol lowering drugs in reducing mortality in ESRD patients are
      lacking. While it seems reasonable to suspect that dyslipidemia and its treatment
      in ESRD patients will affect CV morbidity and mortality similar to that in the
      general population, recent studies have suggested that this may not be the case.
      Furthermore, the pharmacokinetics of lipid lowering drugs are altered in patients
      with ESRD and must be considered when treating this group of patients. This
      article reviews the major classes of drugs used to treat dyslipidemia,
      emphasizing their role in patients with ESRD.

PMID- 16970738
TI  - A patient-focused approach to thrombolytic use in the management of catheter
      malfunction.
AB  - Thrombus-related catheter malfunction is a significant problem for catheter
      dependent dialysis patients. The primary medical intervention is the local
      luminal installation of thrombolytic agents (TLAs). There are three major TLA
      installation methodologies: locking, push, and infusion protocols. A systematic
      literature review of existing TLA protocols for treating dialysis catheter
      malfunction was performed using the PubMed and EMBASE (Drugs and Pharmacology)
      databases from the time of each database's inception to August 2005. Thrombolytic
      administration was then categorized according to the patient's clinical need: (1)
      an acute/immediate requirement, such as when malfunction prohibits dialysis
      initiation, and (2) rescue therapy, such as when the thrombus threatens to
      significantly impair current or subsequent dialysis clearance. Published TLA
      protocols are discussed in the context of their clinical requirement (acute or
      rescue therapy). A unifying clinically relevant management algorithm that
      considers the etiology of catheter malfunction as being thrombus related or not,
      and an approach to TLA use based on clinical presentation is described. This
      algorithm was developed after a systematic review of the literature. The
      application of this treatment algorithm requires prospective validation and
      study.

PMID- 16970740
TI  - The role of continuous renal replacement therapy in the treatment of poisoning.
AB  - Extracorporeal elimination of drugs and toxins is a critical component in the
      management of poisonings, though specific techniques and indications remain a
      matter of debate. Conventional hemodialysis is frequently the treatment of choice
      because of its widespread availability and proven effectiveness for certain drugs
      and toxins. With the increased availability of continuous renal replacement
      therapy (CRRT) modalities, there is yet another therapeutic option, but one that
      has yet to find a definitive role in this field. The continuous nature of these
      therapies is attractive for the management of acute renal failure, but the
      relatively slower clearance rates as compared to conventional hemodialysis is a
      distinct drawback in patients with acute xenobiotic-induced toxicity. There are
      abundant case reports as well as a few small case series in the medical
      literature documenting the use of CRRT, but specific techniques and the clinical
      outcomes vary considerably. Therefore one cannot draw definitive conclusions
      regarding benefit. Some patients, particularly those who are hemodynamically
      unstable and are not candidates for conventional hemodialysis, may warrant a
      trial of CRRT. However, at the present time, routine use for the treatment of
      poisoning is not supported. Controlled trials to better clarify its role would be
      beneficial, though such studies would be extremely difficult to conduct in this
      field. We believe that the intelligent application of extracorporeal modalities
      requires a thorough knowledge of drug pharmacokinetics, of the techniques
      utilized, and a skeptical analysis of the available literature.

PMID- 16970741
TI  - Use of antiepileptic drugs in patients with kidney disease.
AB  - The number of medications used to treat different types of seizures has increased
      over the last 10-15 years. Most of the newer antiepileptic drugs (AEDs) are
      likely to be unfamiliar to many nephrologists. For both the older and newer AEDs,
      basic pharmacokinetic information, recommendations for drug dosing in patients
      with reduced kidney function or who are on dialysis, and adverse renal and fluid
      electrolyte effects are reviewed. Newer AEDs are less likely to have significant
      drug-drug interactions than older agents, but are more likely to need dosage
      adjustment in patients with reduced kidney function. The most common renal
      toxicities of these drugs include metabolic acidosis, hyponatremia, and
      nephrolithiasis; interstitial nephritis and other adverse effects are less
      common. Little is known about the clearance of most of the newer AEDs with high
      efficiency hemodialyzers or with peritoneal dialysis. Monitoring of drug levels
      when available, careful clinical assessment of patients taking AEDs, and close
      collaboration with neurologists is essential to the management of patients taking
      AEDs.

PMID- 16970742
TI  - Successful treatment of the chronically thrombosed dialysis access graft:
      resuscitation of dead grafts.
AB  - The most common contributing cause of thrombosis of an arteriovenous graft (AVG)
      in the hemodialysis patient is the presence of venous stenosis. In the face of a
      recovery of renal function either spontaneously or as a result of renal
      transplantation, an AVG commonly thromboses. In cases in which the AVG was
      recently placed, it is unlikely to have had a significant anatomic lesion at the
      time function was lost. Even though the access that has been left untreated has
      become a "dead" AVG, it offers an opportunity for "resuscitation." Thirteen cases
      that met the specific criteria of being placed only a short period of time prior
      to thrombosis (3 weeks to 6 months), thrombosing after a return of renal function
      and having been left untreated (3 months to 8 years) were attempted over a 12
      year period. The technique applied was modified from the one routinely used based
      on the presumption that very little or no thrombus was present. The effort was
      met with success in 8 of the 13 patients. After being opened, the AVG appeared to
      follow the same patency pattern as other AVGs. It appears that attempting
      restoration of function of an AVG meeting these criteria may be indicated.
      Limited experience using this approach in AVGs that do not meet these specific
      criteria has uniformly met with failure.

PMID- 16970743
TI  - Interventional nephrology in a federal hospital: economics of health care.
AB  - Interventional nephrology is now an accepted subspecialty of nephrology that is
      revolutionizing the standard of care for renal failure patients. Interventional
      nephrology deals with the placement of tunneled cuffed catheters (TCCs) and
      maintenance of permanent vascular accesses, thus assisting in timely care. Prior
      to 2000 most end-stage renal disease (ESRD) patients from the Overton Brooks
      Veterans Affairs Medical Center (OBVAMC) were referred to an outlying hospital
      for TCC placement and endovascular procedures (EVPs) of permanent dialysis
      access. The referral process was cumbersome for the patients and expensive to the
      Medicine Service. OBVAMC started an interventional nephrology service in 2000.
      The current study reports the financial benefits of starting an interventional
      nephrology service at our institution. All procedures performed during the period
      from April 2000 to April 2004 were analyzed. The procedures were performed in the
      cardiac catheterization laboratory. The total payment (physician's and hospital
      fees) to the referral hospital for procedures prior to April 2000 was used to
      estimate the average savings to the Medicine Service over the last 4 years. A
      total of 129 TCCs and 43 EVPs were performed during this period. The estimated
      expense to OBVAMC would have been US dollars 603,978 for TCCs and US dollars
      288,100 for EVPs based on charges prior to April 2000. The actual expense to the
      hospital, including facility fees and disposables, was US dollars 156,013. The
      net savings to OBVAMC over the last 4 years was US dollars 736,065.
      Interventional nephrology provided to a small population of renal failure
      patients in a tertiary federal health care facility has resulted in huge savings
      for the hospital. Increasing awareness of this procedural aspect of nephrology
      benefits not only the patients, but also helps ease the financial burden of ever
      escalating health care costs.

PMID- 16970744
TI  - Optimal timing for secondary arteriovenous fistula creation: devastating effects
      of delaying conversion.
AB  - A chronic hemodialysis patient was referred to interventional nephrology for
      evaluation of arteriovenous access dysfunction. The patient had been receiving
      hemodialysis using a left forearm brachiobasilic loop graft for the past 3 years.
      Physical examination revealed a hyperpulsatile graft. Angiography documented a
      critical stenosis at the vein-graft anastomosis and a well-developed basilic vein
      from the elbow to the axillary region. Central veins were patent all the way to
      the right atrium. All attempts to navigate the wire across the stenosis failed.
      The patient was educated and counseled regarding the possibility of surgical
      creation of a secondary arteriovenous fistula (AVF). The images obtained were
      shared and discussed with the surgeon. A plan to create a secondary AVF using the
      basilic vein in the arm was made. A few months later the patient was referred to
      interventional nephrology, this time for thrombectomy of the same left arm loop
      graft. Thrombectomy could not be performed and a right internal jugular tunneled
      catheter was inserted. The patient again was referred to the surgeon for AVF
      creation. Six weeks later the patient was seen in the interventional laboratory
      for removal of the right internal jugular tunneled catheter. It was noted that
      instead of a fistula, the patient had received a right forearm brachiocephalic
      loop graft. Devastating consequences, such as the lost opportunity to create a
      fistula, insertion of a tunneled dialysis catheter, arteriovenous graft
      placement, exhaustion of available sites for fistula creation, and exposure to
      increased morbidity and mortality associated with grafts and catheters, can
      result if the opportunity to create a secondary AVF is not availed in a timely
      manner. This concept must be understood by every member of the vascular access
      team.

PMID- 16970745
TI  - Interdialytic weight gain: implications in hemodialysis patients.
AB  - Interdialytic weight gain (IDWG) is an easily measurable parameter in the
      dialysis unit, routinely assessed at the beginning of the dialysis session. It is
      used along with clinical symptoms and signs and predialysis blood pressure
      readings to make decisions regarding the amount of fluid removal during a
      dialysis session. IDWG is also used as a basis for fluid and salt intake
      recommendations. However, advising fluid and salt restriction based solely on
      IDWG may not be appropriate because of its status as a nutritional indicator, as
      well. Very few studies have been designed to determine the direct effect of IDWG
      on morbidity and mortality. Any such effect is confounded by residual renal
      function and various comorbidities, the effects of which might be difficult to
      separate from those of IDWG. Most attempts to control IDWG have concentrated on
      requiring patients to reduce fluid and dietary salt intake. Although there does
      not seem to be a consensus at this point, it is likely that within the lower
      values of IDWG (less than 5.7% of dry weight), tighter control of fluid and salt
      intake might not be warranted since these values may reflect higher protein and
      calorie intake, indicating better nutritional status.

PMID- 16970747
TI  - A case of fatal cardiac tamponade during hemodialysis.
AB  - A 27-year-old Hispanic man with a history of hypertension and end-stage renal
      disease for 4 years became unresponsive, apneic, and pulseless during
      hemodialysis. During his 4 year period on dialysis, vascular access had become
      increasingly difficult and ultimately a transhepatic catheter had been placed 9
      months prior to this event. Resuscitation was unsuccessful. At autopsy, death was
      determined to be due to cardiac tamponade secondary to perforation of the right
      atrium by the transhepatic catheter. Cardiac tamponade is a rare cause of sudden
      death during hemodialysis with a long-standing catheter.

PMID- 16970748
TI  - Pain and swelling at a Tenckhoff catheter tunnel site.

PMID- 16970750
TI  - That catheter is going to cost you!

PMID- 16970751
TI  - Abstracts of the XXIV Annual Scientific Meeting of the British Blood Transfusion
      Society. September 21-23, 2006. Bournemouth, United Kingdom.

PMID- 16970752
TI  - Ophthalmic genetics: complexity in paediatric vitreoretinopathies.

PMID- 16970753
TI  - Creutzfeldt-Jakob disease: perceptions and realities of risk.

PMID- 16970754
TI  - Supraorbital nerve block in trabeculectomy surgery: an observational case series.
AB  - Thirteen patients completed a visual analogue pain scale after trabeculectomy
      with topical anaesthesia and a supraorbital nerve block with 2 mL of lignocaine
      2%. Ease of surgery was graded on a scale of 0-5. Inadvertent eye movements and
      episodes of orbicularis spasm were recorded. Statistical analysis was performed
      using STATA software. Median pain score (range) during delivery of anaesthesia
      was 2 (1-5), during surgery was 0 (0-4) and postoperatively was 0 (0-3). Pain
      scores after surgery were significantly lower than during delivery of anaesthesia
      (Wilcoxon signed rank test, P = 0.0289). Three subjects had inadvertent eye
      movements with ease of surgery recorded as 1 of 5 in 12 cases and 2 of 5 in one
      case. The novel application of this anaesthetic technique offers adequate
      analgesia in trabeculectomy surgery. However, a larger scale comparative trial is
      needed to further evaluate the value of this technique.

PMID- 16970755
TI  - Calculation of intraocular lens power after corneal refractive surgery.
AB  - PURPOSE: Underestimation of required intraocular lens (IOL) power with resultant
      hyperopia is common in post-corneal refractive surgery eyes. A number of methods
      to minimize error have been proposed but most studies have been small and
      theoretical. METHODS: We retrospectively reviewed 34 eyes that had undergone
      routine phacoemulsification and IOL implantation after photorefractive
      keratectomy or laser in situ keratomileusis. Sixteen eyes were included in the
      final analysis. Using known pre- and postoperative data, four methods were used
      to obtain keratometric values combined with three common IOL formulae (Holladay
      2, SRK/T and Hoffer Q) and Koch's published Double-K nomogram. The Double-K
      method was also used in conjunction with the Holladay 2 formula. Target
      refractions were calculated and then compared to actual postoperative results.
      RESULTS: The Clinical History method at the spectacle plane produced the lowest
      mean K-values. Shammas adjustment formula combined with the Holladay 2 and Hoffer
      Q produced results closest to emmetropia. The Double-K methods produced the least
      number of hyperopic results. Overall, all methods would have resulted in
      unacceptably high rates of hyperopia and deviation from target refraction.
      CONCLUSIONS: No method produces acceptably consistent results because modern IOL
      formulae were designed for presurgical eyes. Accuracy will only be improved when
      new IOL formulae based on the anatomy of postrefractive eyes become available.
      Shammas adjustment formula and regression formulae are viable alternatives
      especially when there is a lack of preoperative data. The Double-K methods are
      best suited to avoiding a hyperopic surprise.

PMID- 16970756
TI  - Transplantation of ocular tissue from a donor with sporadic Creutzfeldt-Jakob
      disease.
AB  - BACKGROUND: One definite, one probable and several possible transmissions of
      sporadic Creutzfeldt-Jakob disease (sCJD) have followed corneal transplantation.
      We report an incident in the UK in 1997 in which both corneas and scleras from a
      donor, subsequently confirmed to have had sCJD, were transplanted. The final
      clinical outcome for two surviving recipients is still not yet known. CASE
      REPORT: In 1997, a 56-year-old woman died from biopsy-proven carcinoma of the
      bronchus. Both eyes were donated for transplantation. Shortly before she died,
      she had developed neurological symptoms thought to be due to brain metastases.
      However, the final result of a neurological post-mortem examination revealed
      evidence of sCJD. By this time the corneas had been transplanted, one 3 months
      previously into a 40-year-old man for keratoconus and the other 4 months
      previously into an 85-year-old woman for Fuchs' dystrophy. In addition, both
      scleras had been transplanted into a 36-year-old man undergoing oculoplastic
      reconstructive surgery. The surgeons and patients were informed and removal of
      tissue was advised but undertaken in only two of the patients.
      Immunohistochemistry failed to demonstrate the presence of the abnormal form of
      the prion protein in explanted tissue. CONCLUSIONS: Eight years after the event,
      two patients remain free of symptoms suggestive of iatrogenic CJD
      (http://www.cjd.ed.ac.uk/criteria.htm). The third having died aged 92 years, some
      7 years after surgery, showing signs of dementia not considered indicative of
      iatrogenic CJD. Nevertheless this adverse incident attracted substantial
      publicity. Coupled with continuing concerns in the UK about person-to-person
      transmission of variant CJD, this has lead to a number of important consequences
      in donor eye retrieval, ocular tissue banking and transplantation.

PMID- 16970758
TI  - Iris colour, optic disc dimensions, degree and progression of glaucomatous optic
      nerve damage.
AB  - PURPOSE: To evaluate whether iris colour influences size and shape of the optic
      nerve head and risk for glaucoma progression. METHODS: The hospital-based
      observational study included 1973 eyes of 1012 Caucasian subjects with ocular
      hypertension or chronic open-angle glaucoma. For all patients, colour stereo
      optic disc photographs were evaluated, and corneal pachymetry and achromatic
      perimetry were performed. Main outcome measures were optic nerve head parameters,
      the development or progression of visual field defects and iris colour. RESULTS:
      In most of the study groups, size of the optic disc, neuroretinal rim, alpha zone
      and beta zone of parapapillary atrophy, retinal vessel diameter and central
      corneal thickness did not differ significantly between eyes with blue, green,
      brown and mixed iris colour. In the normal-pressure glaucoma group, neuroretinal
      rim area was smallest in the population with mixed-coloured eyes and largest in
      the group of eyes with brown irides (P = 0.001 after correction for inter-eye
      dependency and multiple testing). For the ocular hypertensive subjects and
      glaucoma patients with follow-up examinations, the rate of development or
      progression of glaucomatous visual field loss was not significantly associated
      with iris colour (P = 0.060). CONCLUSIONS: In Caucasian subjects, iris colour
      does not have a major association with the size of the optic nerve head
      structures, central corneal thickness and retinal arterial diameter. In Caucasian
      patients with ocular hypertension or chronic open-angle glaucoma, an influence of
      iris colour on the risk for development or progression of glaucomatous visual
      field defects could not be confirmed.

PMID- 16970759
TI  - Visual outcomes for optic nerve sheath fenestration in pseudotumour cerebri and
      related conditions.
AB  - BACKGROUND: To determine the efficacy and safety of optic nerve sheath
      fenestration, and to identify factors predicting visual field (VF) and visual
      acuity (VA) in patients with progressive pseudotumour cerebri syndrome. METHODS:
      This retrospective observational case series studied 51 eyes of 32 patients with
      pseudotumour cerebri syndrome, by chart review and comparison of preoperative and
      postoperative examinations. Main outcome measures included VF, VA and
      complications. RESULTS: Postoperative VF mean deviation scores improved (P =
      0.03) within 6 months when compared with preoperative VF. Multiple regression
      analysis demonstrated that eyes with mean deviation > or = -20 dB were associated
      with improved or stabilized VA at 6 months, odds ratio 7.5 and confidence
      interval (1.2, 46.1), P = 0.03. Eyes with VF defects outside 10 degrees of
      fixation were associated with improved or stabilized VF at 6 months odds ratio
      9.7, 95% confidence interval 1.1, 85.9, P = 0.04. Five patients developed self
      limiting complications from surgery. CONCLUSIONS: Optic nerve sheath fenestration
      is safe and effective in stabilizing or improving VF and VA in the short to
      medium term. Patients with mild VF loss improved following surgery, and patients
      with severe VF loss stabilized following surgery.

PMID- 16970757
TI  - Nosocomial infection in an eye hospital: incidence and occurrence patterns.
AB  - PURPOSE: To describe the incidence and occurrence patterns of nosocomial
      infections in a large eye hospital over a 6-year period. METHODS: Medical records
      of 94,013 consecutive inpatients admitted to Zhongshan Ophthalmic Centre,
      Guangzhou, China, from 1996 to 2002, were reviewed. Demographic data and
      infection diagnoses were collected. Nosocomial infection was defined as an
      infection that was absent during preadmission assessments but detected at least
      48 h after admission to the hospital, or occurred after surgical procedures
      performed within the hospital. RESULTS: The cumulative incidence of nosocomial
      infections over a 6-year period was 0.28%. The most common infections were acute
      conjunctivitis (45.5%) and upper respiratory tract infection (36.4%), followed by
      suppurative endophthalmitis (8.3%). Patients with acute conjunctivitis were
      predominantly adults aged from 15 to 59 years (60%), while patients with upper
      respiratory tract infection were predominantly children of 14 years or younger
      (74.0%), and those with endophthalmitis predominantly older persons 60 years or
      older (68.2%). Conditional pathogenic bacteria, mainly gram-positive, were
      responsible for most suppurative endophthalmitis cases. CONCLUSIONS: Although
      nosocomial infection incidence is relatively low in this eye hospital, our data
      suggest that different subgroups of patients are prone to certain types of
      infection. Specific preventive strategies targeting different subgroups of
      inpatients may further reduce the infection incidence.

PMID- 16970760
TI  - Telemedicine-friendly, portable tonometers: an evaluation for intraocular
      pressure screening.
AB  - PURPOSE: To evaluate the intraocular pressure (IOP) readings from two portable,
      telemedicine-friendly tonometers for suitability in glaucoma screening. METHODS:
      213 eyes of 107 consenting patients attending an eye clinic were tested with an I
      care tonometer and a Pulsair-Easy Eye puff-air tonometer. Gold standard IOP was
      measured with a Goldmann applanation tonometer (GAT). Effect of central corneal
      thickness, anterior chamber depth and refractive errors on IOP measurements were
      also analysed. RESULTS: The mean difference of IOP by GAT and both the portable
      tonometers was +/- 2.2 mmHg. The analysis indicates minimal difference between
      IOP readings of both the portable tonometers. The mean difference between two
      consecutive readings by I-care was 0.01 mmHg. Using 21 mmHg as a threshold for
      suspected glaucoma, both the portable digital tonometers reported a sensitivity
      of 38% and specificity of >95%. In the subjects studied, central corneal
      thickness had statistically significant influence on IOP measurements while
      refractive errors and anterior chamber depth had no significant influence on IOP
      measurements with any tonometry. CONCLUSION: The IOP readings by both portable
      tonometers are comparable and were within clinically acceptable range from GAT.
      These portable tonometers are useful tools for IOP screening.

PMID- 16970761
TI  - An assessment of recycled spectacles donated to a developing country.
AB  - BACKGROUND: A rapid assessment methodology was used to determine the suitability
      of donated recycled spectacles for the Pacific nation of Tuvalu. METHODS:
      Spectacles (102) from a donated cache were examined. Those with astigmatism of >
      1.00 D, anisometropia of > 0.50 D, significant central lens scratches, broken
      frame, poor cosmetic fit and comfort, or unsuitable frame appearance were
      excluded. The refractive errors (> or = +/-0.50 D distance or near) of 320
      Tuvaluans were determined. RESULTS: Of the spectacles, 62.7% had > 1.00 DC and/or
      > 0.50 D anisometropia, 30% were broken and/or scratched and 50% were
      uncomfortable or cosmetically unacceptable. Only 13% were optically satisfactory,
      physically intact, and cosmetically appropriate. Of the people, 8.8% had > 1.00
      DC and/or > 0.50 D anisometropia, requiring custom-made spectacles. A further
      8.1% needed a -0.50 to -2.00 DS correction, for which there were no spectacles in
      this cache. For the other 83.1% (266), if the cache contained at least 5538
      spectacles, each would eventually find a suitable pair. CONCLUSION: If the scheme
      to Tuvalu is typical, refractive error will remain largely uncorrected if only
      donated recycled spectacles are available. No amount of efficiency and
      effectiveness in the delivery chain can justify the output and outcome of this
      recycling scheme.

PMID- 16970762
TI  - Cicatricial ectropion: repair with myocutaneous flaps and canthopexy.
AB  - BACKGROUND: To evaluate the effectiveness of myocutaneous upper eyelid flaps
      combined with canthopexy to treat cicatricial lower eyelid ectropion. METHODS: A
      prospective non-comparative case series undertaken in a private practice setting.
      Consecutive patients with moderate lower eyelid cicatricial ectropion and upper
      eyelid dermatochalasis underwent transfer of a bipedicle or monopedicle flap from
      the upper eyelid combined with canthopexy. The main outcome measures included the
      occurrence of complications, eyelid position and cosmesis. RESULTS: Sixty-two
      consecutive cases of cicatricial ectropion repair using myocutaneous flaps and
      canthopexy. After a mean follow up of 20 months, 58 (93.5%) of the cases had the
      lower lid punctum facing posterosuperior into the tear lake, showed lid globe
      apposition and satisfactory eyelid position. There was mild recurrence of
      cicatricial ectropion in four patients (6.5%). There were no cases of graft
      failure or granuloma formation. CONCLUSION: The use of a myocutaneous flap from
      the upper eyelid combined with a canthopexy suspension suture for repair of
      cicatricial ectropion may offer good eyelid position and function. This technique
      has the advantage of avoiding full thickness blepharotomy and was associated with
      a low incidence of early recurrence.

PMID- 16970763
TI  - Mutations in the NDP gene: contribution to Norrie disease, familial exudative
      vitreoretinopathy and retinopathy of prematurity.
AB  - BACKGROUND: To examine the contribution of mutations within the Norrie disease
      (NDP) gene to the clinically similar retinal diseases Norrie disease, X-linked
      familial exudative vitreoretinopathy (FEVR), Coat's disease and retinopathy of
      prematurity (ROP). METHODS: A dataset comprising 13 Norrie-FEVR, one Coat's
      disease, 31 ROP patients and 90 ex-premature babies of <32 weeks' gestation
      underwent an ophthalmologic examination and were screened for mutations within
      the NDP gene by direct DNA sequencing, denaturing high-performance liquid
      chromatography or gel electrophoresis. Controls were only screened using
      denaturing high-performance liquid chromatography and gel electrophoresis.
      Confirmation of mutations identified was obtained by DNA sequencing. RESULTS:
      Evidence for two novel mutations in the NDP gene was presented: Leu103Val in one
      FEVR patient and His43Arg in monozygotic twin Norrie disease patients.
      Furthermore, a previously described 14-bp deletion located in the 5'
      unstranslated region of the NDP gene was detected in three cases of regressed
      ROP. A second heterozygotic 14-bp deletion was detected in an unaffected ex
      premature girl. Only two of the 13 Norrie-FEVR index cases had the full features
      of Norrie disease with deafness and mental retardation. CONCLUSION: Two novel
      mutations within the coding region of the NDP gene were found, one associated
      with a severe disease phenotypes of Norrie disease and the other with FEVR. A
      deletion within the non-coding region was associated with only mild-regressed
      ROP, despite the presence of low birthweight, prematurity and exposure to oxygen.
      In full-term children with retinal detachment only 15% appear to have the full
      features of Norrie disease and this is important for counselling parents on the
      possible long-term outcome.

PMID- 16970764
TI  - Immunofluorescence detection of globotriaosylceramide deposits in conjunctival
      biopsies of Fabry disease patients.
AB  - BACKGROUND: Fabry disease is an X-linked disorder due to a deficiency of alpha
      galactosidase A and leads to the accumulation of globotriaosylceramide (Gb3) in
      various cells. The detection of Gb3 deposits may help in the diagnosis. To date,
      no immunofluorescence-specific detection of Gb3 in conjunctival biopsies has been
      reported. The aim of this work was to detect Gb3 accumulation in conjunctival
      biopsies from Fabry patients by immunofluorescence. METHODS: Conjunctival
      biopsies taken from Fabry males and females, before and after enzyme replacement
      therapy, and normal controls were processed for immunofluorescence with a
      monoclonal antibody specific for Gb3. RESULTS: Positive green immunofluorescence
      was observed in all biopsies from Fabry patients before enzyme replacement
      therapy. After 6 months of treatment, immunofluorescence in blood vessels was not
      observed. CONCLUSIONS: Immunofluorescence detection of Gb3 in conjunctival
      biopsies may be a reliable method for the diagnosis of Fabry disease in family
      members, and to evaluate effectiveness of enzyme replacement therapy.

PMID- 16970765
TI  - Ciliary body medulloepithelioma: clinical, ultrasound biomicroscopic and
      histopathologic correlation.
AB  - A 3-year-old girl presented with a distorted pupil and decrease of visual acuity.
      A ciliary body mass at the superior-temporal quadrant could be seen at slit-lamp
      examination. Ultrasound biomicroscopy revealed a lesion with lobulated surface,
      arising at the ciliary body, composed of compact and cystic areas. An
      iridocyclectomy was performed but the tumour recurred after a few months. The eye
      was then enucleated. Histopathologic evaluation showed sheets and cords of
      proliferated medullary epithelium. Cystic spaces and Flexner-Wintersteiner
      rosettes were also seen. Those findings correlated well with ultrasound
      biomicroscopic images. The knowledge of echographic characteristics can
      significantly assist in the diagnosis of medulloepithelioma of the ciliary body.

PMID- 16970766
TI  - Presumed eccrine carcinoma metastatic to the choroid.
AB  - The purpose of this article is to describe a patient with presumed choroidal
      metastasis from an eccrine adenocarcinoma of the scalp. A 45-year-old Caucasian
      woman presented with decreased visual acuity. Ophthalmologic examination was
      unremarkable. Her past medical history was significant for eccrine carcinoma of
      the scalp. The patient developed bilateral cervical lymph node metastases, and
      received chemotherapy and radiotherapy. She had recurrence of the scalp lesion
      and developed bone metastasis. The patient was again referred to an
      ophthalmologist owing to reduced visual acuity. Multiple choroidal metastases
      were detected in right eye, and one metastatic lesion in left eye. The patient
      passed away 2 months after choroidal metastases. This is the first report of
      choroidal metastases from an eccrine carcinoma. This is a rare aggressive
      neoplasm with poor outcome in most cases of metastatic disease, and in this case
      report, uveal metastasis was indicative of poor prognosis.

PMID- 16970767
TI  - Ophthalmology in proverbs and aphorisms.
AB  - After a comprehensive review of available texts and literature covering five
      millennia, the authors present a collection of ophthalmic proverbs and aphorisms
      with an examination of their applicability within current medical knowledge. A
      total of 74 ophthalmic proverbs and aphorisms were retrieved from 130 texts and
      divided into seven categories: (i) importance of vision ('The eyes, like
      sentinels, hold the highest place in the body'); (ii) definition of blindness and
      anatomical observations ('The eye is protected by the lashes, eyebrows, and
      orbit'); (iii) diseases of the eye such as presbyopia, sensitivity to light and
      dry eye ('Tear in the eye is jewel'); (iv) the eye as a window of the body; (v)
      vulnerability of the eye ('The eye cannot oppose an awl'); (vi) health behaviours
      and protection of sight ('Be gentle with two: women and eyes'), and finally; and
      (vii) nutrition and vision ('Carrots improve vision'). The majority of these
      proverbs and aphorisms can be used as a guide, not for prognosis, diagnosis or
      cure, but rather for ocular health promotion.

PMID- 16970772
TI  - Role of topical chemotherapy for primary acquired melanosis and malignant
      melanoma of the conjunctiva and cornea: review of the evidence and
      recommendations for treatment.
AB  - Surgical excision with cryotherapy is a well-established treatment option for
      malignant melanoma or primary acquired melanosis (PAM) with atypia of the
      conjunctiva and cornea. Topical chemotherapeutic agents such as mitomycin C (MMC)
      however, are increasingly finding use in clinical practice. A search was
      performed of Medline and Pubmed databases for English language articles from 1980
      to the present in this field. Relevant studies were reviewed with regards to
      treatment regimen, rates of recurrence and metastasis, side effect profile and
      length of follow up. A total of 22 and 16 unique cases of biopsy proven PAM with
      atypia and malignant melanoma, respectively, treated with topical MMC were
      identified. Topical MMC was well tolerated and shows considerable promise,
      particularly in the treatment of diffuse PAM with atypia. However, long-term data
      are lacking and further studies are required.

PMID- 16970774
TI  - Amniotic membrane to the rescue of partially necrosed dermis fat graft.
AB  - A 25-year-old woman underwent dermis fat graft on the right side for persistent
      ocular pain with her polymethylmethacrylate (PMMA) spherical orbital implant. One
      week later she developed dermal necrosis of the dermis fat graft with potentially
      devastating fat atrophy if left uncovered. Amniotic membrane graft epithelial
      side up was sutured to the conjunctiva surrounding the fat. 2 weeks later the
      graft epithelialized with preservation of fat. Role of amniotic membrane graft as
      a routine lining over dermis fat grafts to promote conjunctival healing and
      prevent fat exposure needs to be studied in prospective studies.

PMID- 16970773
TI  - Giant cell arteritis presenting with scalp necrosis--the timing of temporal
      artery biopsy?
AB  - Scalp necrosis in patients presenting with clinical features suggestive of giant
      cell arteritis is rare. The immediate concern is that temporal artery biopsy
      might further compromise scalp circulation. We report a case of extensive scalp
      necrosis caused by giant cell arteritis. Temporal artery biopsy performed after
      14 days was not associated with any significant damage and still provided florid
      evidence of the disease. Rapid and complete scalp healing was achieved with
      aggressive treatment.

PMID- 16970775
TI  - Persistent serous retinal detachment after radial optic neurotomy.
AB  - We report the case of a patient presenting with serous retinal detachment
      following radial optic neurotomy for central retinal vein occlusion. Initially,
      the retinal detachment was successfully treated by a second vitrectomy and laser
      coagulation. After reabsorption of the gas tamponade, a recurrence of the retinal
      detachment was seen with no detectable retinal break. Although other mechanisms
      should be taken into account, this case indicates that it is possible to create a
      fistula between the subarachnoid and subretinal space. We conclude from this
      observation that special attention should be paid to the depth of the radial
      incision into the optic nerve head.

PMID- 16970777
TI  - Primary treatment of choroidal amelanotic melanoma with photodynamic therapy-
      comment.

PMID- 16970778
TI  - Affordable ready-made spectacles for use in blindness prevention programmes:
      setting standards of quality.

PMID- 16970779
TI  - Observations on offshore ophthalmic clinics.

PMID- 16970781
TI  - High CD4/CD45RO+ and CD8/CD45RO+ frequencies in children with vaccine-modified
      measles.
AB  - BACKGROUND: Despite availability and wide vaccine coverage, measles infections
      still occur especially in developing countries. An outbreak of measles occurred
      among previously immunized older Ghanaian children who had milder clinical
      symptoms with measles-specific IgG antibodies that could have been attributed to
      secondary vaccine failure, suggesting that the infection was vaccine-modified
      measles (VMM). METHODS: Two-color immunophenotyping of the peripheral blood
      mononuclear cells was performed at acute, recovery and convalescence phases for
      19 VMM patients (mean age 6.2 +/- 3.5 years) using flow cytometry, and compared
      with that of 20 healthy, sex- and age-matched controls. RESULTS: The results
      showed a significantly higher memory helper (CD4(+)/CD45RO(+)) cell frequency and
      increased suppressor cell (CD8(+)/CD45R0(+)) frequency in VMM patients compared
      to healthy controls. There were no complications and all the patients recovered
      completely. CONCLUSIONS: These findings show that the mild symptoms in patients
      with VMM may have correlated with the increase of memory T cells, which is in
      sharp contrast with previous reports on acute measles infection. This may suggest
      that the intact immunologic memory cells could have been crucial for the
      resolution of VMM.

PMID- 16970782
TI  - Microbial colonization of nebulizers used by asthmatic children.
AB  - BACKGROUND: The aim of the present study was to determine the microbial
      colonization of nebulizers used at home by asthmatic children, and to investigate
      their parents' cleaning and maintenance routines. METHODS: The nebulizer
      equipment used at home by 39 asthmatic children was examined. Swabs taken from
      the inner surface of the reservoir cups, face masks and filters were cultured.
      Results were recorded as mean number of colony-forming units per cultured
      surface. Parents were interviewed regarding their cleaning and disinfection
      routines. RESULTS: Twenty-six reservoir cups (66.7%), 24 face masks (61.5%), and
      18 filters (78.3%) were found to be contaminated. Pseudomonas aeruginosa was
      isolated from 17 reservoir cups (43.6%) and 12 face masks (30.8%), and
      Staphylococcus aureus from two face masks (5.1%). None of the parents knew that
      the nebulizer has a filter and that it requires periodic cleaning or changing;
      only eight of the parents (20.5%) received maintenance instructions from the
      medical staff, and only 19 (48.7%) cleaned the nebulizer equipment after use.
      CONCLUSION: Home nebulizers are frequently colonized with microorganisms. As
      recommended, nebulizers should be washed after each use and air-blown dry.
      Nebulizer maintenance should be emphasized in educational programs for managing
      asthma.

PMID- 16970783
TI  - Contribution of pulmonary surfactant with inhaled nitric oxide for treatment of
      pulmonary hypertension.
AB  - BACKGROUND: Combined therapy of inhaled nitric oxide (iNO) with pulmonary
      surfactant replacement was reported to improve oxygenation in patients or animal
      models of persistent pulmonary hypertension of the newborn with pulmonary
      surfactant deficiency lung. To evaluate the potential of iNO for the treatment of
      persistent pulmonary hypertension of the newborn, pulmonary arterial pressure
      (PAP) was measured during iNO before and after pulmonary surfactant replacement
      in an animal model of pulmonary hypertension with surfactant deficiency. METHODS:
      Seven newborn piglets were injected with L-nitro-arginine-methylester to produce
      an animal model of pulmonary hypertension. After PAP increased, iNO (30 p.p.m.)
      was introduced. Then iNO was stopped, and animals were subjected to lung lavage
      with saline. After recording the effect of iNO, all animals then received
      exogenous pulmonary surfactant installation. After surfactant treatment, iNO was
      again introduced. RESULTS: Pulmonary arterial pressure and systemic arterial
      pressure were increased significantly by >30% after infusion of L-nitro-arginine
      methylester. During iNO only PAP was reduced significantly. Respiratory system
      compliance decreased significantly after lung lavage, and increased significantly
      after pulmonary surfactant replacement with concomitant increase of PaO2. In
      contrast, significant reduction of PAP with iNO before and after pulmonary
      surfactant replacement were also observed. The reduction ratios of PAP under each
      condition were 75.2 +/- 7.4%, 81.3 +/- 3.1%, and 79.1 +/- 5.3%, respectively (not
      significant among conditions). CONCLUSION: These results suggest that iNO is
      still a potent pulmonary arterial vasodilator even under pulmonary surfactant
      deficiency in an animal model of pulmonary hypertension.

PMID- 16970784
TI  - Serum glucagon-like peptide-2 levels in neonates: comparison between extremely
      low-birthweight infants and normal-term infants.
AB  - BACKGROUND: Glucagon-like peptide-2 (GLP-2) arises from proglucagon within
      enteroendocrine L cells of the small and large intestines, and its physiological
      roles have been gradually elucidated. However, the circulating GLP-2 levels in
      human neonates are still unknown. The aim of the present study was to measure
      serum GLP-2 levels in extremely low-birthweight (ELBW) infants and normal-term
      infants, and to compare these values between the two groups. METHODS: Blood
      samples were collected and serum GLP-2 concentrations measured, from 15 ELBW
      infants at three stages (stage I, before initial feeding after birth; stage II,
      point at which milk intake reached 100 mL/kg per day; stage III, corrected 40
      weeks of gestation), and from 30 normal-term infants at two stages (stages I and
      II). RESULTS: No significant difference in basal GLP-2 values at stage I (before
      initial feeding) was found between ELBW infants and normal-term infants (7.37 +/-
      0.95 ng/mL vs 9.47 +/- 0.94 ng/mL). However, in ELBW infants, serum GLP-2
      concentrations at stage II were significantly increased, compared with those at
      stage I (P < 0.0001). In normal-term infants, serum GLP-2 concentrations at stage
      II were also significantly increased compared with those at stage I (P < 0.001).
      CONCLUSION: The results suggest that initial feeding stimulates secretion of
      serum GLP-2 in neonates. In addition, the secretion mechanism of GLP-2 is
      considered to be established at 24 weeks of gestation at the latest.

PMID- 16970785
TI  - Determinants of birthweight inequalities: population-based study.
AB  - BACKGROUND: The aim of this paper is to study the whole spectrum of birthweight
      in a population-based birth cohort in order to document the role played by social
      factors, which complement physiological and behavioural factors, in the
      development of birthweight inequalities at the population level. METHODS: The
      analyses were performed with data from the 'Quebec Longitudinal Study of Child
      Development 1998-2002 (QLSCD)'. The study follows a representative sample (n =
      2103) of the children born in 1998 in the Canadian province of Quebec. RESULTS:
      Multivariate analyses adjusted for gestational age and mother's age indicate that
      mean birthweight was higher for boys than girls; improved with birth rank,
      mother's body mass index (BMI), and family socioeconomic status; and was lower
      for children of smoking mothers. Compared with children born to non-smoking
      mothers of higher socioeconomic status, the odds of having a low birthweight were
      between 6 and 12 times higher for children born to smoking mothers of lower or
      middle socioeconomic status. When maternal smoking status and mother's BMI are
      combined, socioeconomic status could still be seen to have a positive effect on
      mean birthweight except for overweight or obese smoking mothers, among whom the
      relationship between socioeconomic status and mean birthweight was reversed. In
      families of lower socioeconomic status, maternal smoking was the most important
      factor in birthweight inequalities, and in families of higher socioeconomic
      status, mother's BMI was the most important factor in birthweight inequalities.
      CONCLUSION: This research is not only important for children in developed
      nations, but also for those in developing countries, where high birthweight and
      obesity are becoming more prevalent.

PMID- 16970786
TI  - Lipid peroxidation in cord blood and neonatal outcome.
AB  - BACKGROUND: Periventricular-intraventricular hemorrhage, necrotizing
      enterocolitis, chronic lung disease and retinopathy of prematurity have been
      referred to as oxygen radical diseases (ORD) because they are thought to be
      related to excess oxidant stress relative to anti-oxidant defenses in premature
      infants. 8-Isoprostane is a product of lipid peroxidation that can be used as a
      measure of free radical exposure or injury. The aim of the present study was to
      determine whether fetal oxidant stress is associated with adverse effects in
      preterm infants. METHODS: Mothers delivering at gestational age <37 weeks were
      recruited. Umbilical arterial and venous cord blood samples were collected and 8
      isoprostane levels measured. Levels of 8-isoprostane in cord blood were
      correlated with maternal and perinatal variables, neonatal mortality, and the
      development of one or more ORD. RESULTS: Umbilical cord venous, but not arterial,
      8-isoprostane levels were associated with mortality and the development of one or
      more of the ORD. After controlling for gestational age, for each unit change in
      the log value of 8-isoprostane in venous cord blood the odds of mortality were 12
      (95% confidence interval [CI]: 1-223) and oxygen radical disease were 2.7 (95%CI:
      1-7.2). Isoprostane levels were not related to gender, method of delivery, use of
      maternal magnesium or steroids, pregnancy-induced hypertension, or delivery room
      resuscitation. CONCLUSION: Oxidant stress in utero may be an important
      determinant of mortality and morbidity in preterm infants. Elevated umbilical
      venous isoprostane levels suggest that oxidative injury to maternal and placental
      tissues predispose to adverse neonatal outcomes.

PMID- 16970787
TI  - Contact pressure distribution features in Down syndrome infants in supine and
      prone positions, analyzed by photoelastic methods.
AB  - BACKGROUND: Local force distribution supporting the bodyweight of infants with
      Down syndrome (DS) appears to be different from that of healthy controls. The
      purpose of the present study was to establish methods to assess this force
      distribution and to allow therapeutic evaluation of neurological development in
      DS infants prior to walking. METHODS: Contact pressure distribution patterns in
      supine and prone positions were measured by photoelastic methods and were
      compared between DS infants and healthy controls. The DS group included eight
      subjects, seven with regular trisomy 21, and one with a Robertson translocation.
      The controls consisted of 14 neonates, four 4-month-old infants and eight 7-month
      old infants. RESULTS: In both groups, head loading ratio decreased as age
      advanced but the decrement was less in the test group than in the control group.
      When the bodyweight loading ratios were measured in two different lying
      positions, that is, prone and supine, the ratios for prone generally tended to be
      smaller than those for supine in the controls. This kind of difference between
      prone and supine was not seen in the DS group. The bodyweight is somewhat
      sustained with limbs and the limbs loading ratios in the DS group were always
      significantly lower than in the controls. CONCLUSION: Coordinated development of
      weight-supporting limbs seems to be poor in the DS group.

PMID- 16970789
TI  - Bell's palsy and hepatitis infection.

PMID- 16970788
TI  - Transient abnormal myelopoiesis complicated by tumor lysis syndrome.

PMID- 16970790
TI  - Retinochoroidal infarction during the treatment of acute lymphoblastic leukemia.

PMID- 16970791
TI  - Findings of hepatobiliary scintigraphy and liver biopsy in Maroteaux-Lamy
      syndrome presenting as neonatal cholestasis.

PMID- 16970792
TI  - Large cell calcifying Sertoli cell tumor of the testis in a boy with brucellosis.

PMID- 16970793
TI  - Moyamoya disease-induced hemichorea corrected by indirect bypass surgery.

PMID- 16970794
TI  - Aplasia cutis congenita: Successful conservative treatment.

PMID- 16970795
TI  - Successful multiple coils embolization for bilateral patent ductus arteriosus
      with isolated subclavian artery.

PMID- 16970796
TI  - Use of rituximab in chronic childhood immune thrombocytopenic purpura.

PMID- 16970797
TI  - Intracranial hemorrhage in children with idiopathic thrombocytopenic purpura.

PMID- 16970798
TI  - TLR engagement prevents transplantation tolerance.
AB  - In many experimental models, heart, pancreas and kidney allografts are accepted
      long-term following costimulation-targeting therapies, whereas skin, lung and
      intestine resist the induction of tolerance under the same regimens. We noted
      that a common feature of the resistant organs is their constant exposure to
      commensal microbes and hypothesized that these microorganisms may stimulate Toll
      like receptors (TLRs), promote alloresponses and prevent tolerance induction.
      This hypothesis prompts the predictions that TLR engagement at the time of
      transplantation should avert tolerance to heart allografts in animals treated
      with costimulation-targeting therapies, whereas inhibition of TLR signaling
      should promote tolerance to skin allografts under the same conditions. Indeed,
      engagement of a single TLR was sufficient to prevent anti-CD154-mediated long
      term cardiac allograft acceptance and correlated with abolished intragraft
      recruitment of CD4+/FoxP3+ regulatory T cells and the development of linked
      suppression. Conversely, a lack of donor and recipient MyD88-dependent signaling
      led to successful skin allograft acceptance in anti-CD154-treated animals. Thus,
      the status of TLR signaling contributes to the resistance versus susceptibility
      of organs to transplantation tolerance.

PMID- 16970799
TI  - Increasing resistance of tubular epithelial cells to apoptosis by shRNA therapy
      ameliorates renal ischemia-reperfusion injury.
AB  - Renal tubular epithelial cells (TEC) die by apoptosis or necrosis in renal
      ischemia-reperfusion injury (IRI). Fas/Fas ligand-dependent fratricide is
      critical in TEC apoptosis, and Fas promotes renal IRI. Therefore, targeting Fas
      or caspase-8 may have therapeutic potential for renal injury in kidney transplant
      or failure. RNA silencing by short hairpin RNA (shRNA) is a novel strategy to
      down-regulate protein expression. Using this approach, silencing of Fas or
      caspase-8 by shRNA to prevent TEC apoptosis and IRI was evaluated. IRI was
      induced by renal artery clamping for 45 or 60 min at 32 degrees C in
      uninephrectomized C57BL/6 mice. Here, we showed that Fas or pro-caspase-8
      expression was significantly knocked down in TEC by stable expression of shRNA,
      resulting in resistance to apoptosis induced by superoxide, IFN-gamma/TNF-alpha
      and anti-Fas antibody. Inferior vena cava delivery of pHEX-small interfering RNA
      targeting Fas or pro-caspase-8 resulted in protection of kidney from IRI,
      indicated by reduction of renal tubular injury (necrosis and apoptosis) and serum
      creatinine or blood urea nitrogen. Our data suggest that shRNA-based therapy
      targeting Fas and caspase-8 in renal cells can lead to protection of kidney from
      IRI. Attenuation of pro-apoptotic proteins using genetic manipulation strategies
      such as shRNA might represent a novel strategy to promote kidney allograft
      survival from rejection or failure.

PMID- 16970800
TI  - Pancreatic panniculitis associated with allograft pancreatitis and rejection in a
      simultaneous pancreas-kidney transplant recipient.
AB  - Pancreatic panniculitis is an uncommon condition that can occur in association
      with pancreatic disease. We present a case of pancreatic panniculitis in a female
      pancreas-kidney transplant recipient 5 months post-transplant. The patient was on
      standard immunosuppressive medications and had acute rejection of her renal
      allograft. The diagnosis of allograft pancreatitis and rejection presenting with
      pancreatic panniculitis was supported clinically, histopathologically and by
      laboratory and imaging data. This is the fourth case of pancreatic panniculitis
      occurring in a transplant recipient and the first in a simultaneous pancreas
      kidney transplant recipient. It is also the first case associated with allograft
      rejection. Clinicians should be aware that pancreatic panniculitis may be a
      manifestation of underlying allograft pancreatic disease.

PMID- 16970801
TI  - Heparanase induces tissue factor expression in vascular endothelial and cancer
      cells.
AB  - BACKGROUND: Over-expression of tissue factor (TF) and activation of the
      coagulation system are common in cancer patients. Heparanase is an endo-beta-D
      glucuronidase that cleaves heparan sulfate chains on cell surfaces and in the
      extracellular matrix, activity that closely correlates with cell invasion,
      angiogenesis and tumor metastasis. The study was undertaken to investigate the
      involvement of heparanase in TF expression. METHODS: Tumor-derived cell lines
      were transfected with heparanase cDNA and TF expression was examined. The effect
      of exogenous addition of active and inactive heparanase on TF expression and
      activity was studied in tumor cell lines and primary human umbilical vein
      endothelial cells. TF expression was also explored in heparanase over-expressing
      transgenic (Tg) mice. Blast cells were collected from acute leukemia patients and
      TF and heparanase expression levels were analyzed. RESULTS: Over-expression of
      heparanase in tumor-derived cell lines resulted in a 2-fold increase in TF
      expression levels, and a similar trend was observed in heparanase Tg mice in
      vivo. Likewise, exogenous addition of heparanase to endothelial or tumor-derived
      cells resulted in enhanced TF expression and activity. Interestingly, TF
      expression was also induced in response to enzymatically inactive heparanase,
      suggesting that this effect was independent of heparanase enzymatic activity. The
      regulatory effect of heparanase on TF expression involved activation of the p38
      signaling pathway. A positive correlation between TF expression levels and
      heparanase activity was found in blasts collected from 22 acute leukemia
      patients. CONCLUSIONS: Our results indicate that in addition to its well-known
      function as an enzyme paving a way for invading cells, heparanase also
      participates in the regulation of TF gene expression and its related coagulation
      pathways.

PMID- 16970802
TI  - Bax activators potentiate coated-platelet formation.
AB  - BACKGROUND: Activation of platelets with collagen plus thrombin produces a subset
      of cells known as coated-platelets. Coated-platelets retain several alpha-granule
      proteins on their surface, express phosphatidylserine (PS), lose mitochondrial
      potential and release microparticles. OBJECTIVE: A number of these
      characteristics are also observed in apoptotic cells, and this similarity leads
      to the hypothesis that mechanisms controlling initiation of apoptosis might also
      affect generation of coated-platelets. RESULTS: In this report, we demonstrate
      that BH3 mimetics, molecules that facilitate apoptosis by releasing pro-apoptotic
      Bax from its antiapoptotic partner Bcl-2, are able to promote coated-platelet
      formation as monitored by several different markers of these cells. Specifically,
      gossypol and methoxy-antimycin (MAM) promote fibrinogen retention, mitochondrial
      depolarization, and PS exposure upon activation with thrombin plus convulxin, a
      ligand of the glycoprotein VI collagen receptor. Gossypol also potentiates
      microparticle release by convulxin plus thrombin activated platelets although MAM
      does not. In addition, Bax activators together with thrombin generate coated
      platelets, effectively bypassing the requirement for convulxin. CONCLUSION: These
      findings further support a close relationship between apoptotic-like events and
      the production of coated-platelets.

PMID- 16970803
TI  - Circadian clock molecules CLOCK and CRYs modulate fibrinolytic activity by
      regulating the PAI-1 gene expression.
AB  - Disruptions of circadian rhythms are associated with the development of many
      disorders. However, whether a disruption of the circadian clock can cause
      anomalies of the hemostatic balance remains unknown. The present study examines
      coagulation and fibrinolytic activities in circadian clock mutants, a homozygous
      Clock mutant and Cry1/Cry2 double knockout (Cry1/2-deficient) mice. The
      euglobulin clot lysis time (ELT) showed circadian variations that peaked at 21:00
      (early night) in wild-type mice, suggesting that fibrinolytic activity is lowest
      at this time. The ELT was continuously reduced in Clock mutants, while the ELT
      was significantly increased and did not differ between day and night (9:00 and
      21:00) in Cry1/2-deficient mice. The prothrombin time (PT) and activated partial
      prothrombin time (APTT) were constant in all genotypes. To identify which factors
      cause the loss of ELT rhythm, we measured fibrinolytic parameters in Clock mutant
      and Cry1/2-deficient mice. The robust circadian fluctuation of plasma plasminogen
      activator inhibitor 1 (PAI-1) that peaked at early night was damped to trough
      levels in Clock mutant mice. On the other hand, PAI-1 levels in Cry1/2-deficient
      mice remained equivalent to the peak levels of those in wild-type mice at both
      9:00 and 21:00. Circadian changes in plasma PAI-1 levels seemed to be regulated
      at the level of gene expression, because the plasma PAI-1 levels in Clock mutant
      and Cry1/2-deficient mice were closely correlated with the level of PAI-1 mRNA
      transcript in these mice. Plasma plasminogen and hepatic mRNA levels were not
      rhythmic in wild-type mice, and continuously higher in Clock mutant than in wild
      type or Cry1/2-deficient mice. In contrast, the activity and mRNA levels of
      tissue type plasminogen activator (t-PA), plasma levels and mRNA levels of
      plasminogen, and plasma levels of alpha2 plasmin inhibitor (alpha2PI) in all
      genotypes were constant throughout the day. Coagulation parameters such as factor
      VII, factor X, prothrombin and fibrinogen remained constant throughout the day,
      and were not affected by clock gene mutations. These results suggest that
      circadian clock molecules play an important role in hemostatic balance by
      regulating the fibrinolytic systems.

PMID- 16970804
TI  - Intravenous nitroglycerin does not preserve gastric microcirculation during
      gastric tube reconstruction: a randomized controlled trial.
AB  - INTRODUCTION: Complications of oesophagectomy and gastric tube reconstruction
      include leakage and stenosis, which may be due to compromised microvascular blood
      flow (MBF) in gastric tissue. We recently demonstrated that decreased MBF could
      be improved perioperatively by topical administration of nitroglycerin. The aim
      of the present study was to investigate whether nitroglycerin, administered
      intravenously during gastric tube reconstruction, could preserve tissue blood
      flow and oxygenation in the gastric fundus, and reduce the incidence of
      postoperative leakage. METHODS: In this single-centre, prospective, double
      blinded study, we randomized 32 patients scheduled for oesophagectomy into two
      groups. The intervention group received intravenous nitroglycerin during gastric
      tube reconstruction, and the control group received normal saline. Baseline
      values for MBF, microvascular haemoglobin oxygen saturation and microvascular
      haemoglobin concentration were determined at the gastric fundus before and after
      gastric tube construction and after pulling up the gastric tube to the neck.
      RESULTS: MBF and microvascular haemoglobin oxygen saturation decreased similarly
      in both groups during gastric tube reconstruction and were comparable. The
      oesophageal anastomosis was controlled by contrast radiography before discharge
      from the hospital; leakage was observed in two patients (13%) in the
      nitroglycerin group and five patients (31%) in the control group (not
      significant). CONCLUSION: Under stable systemic haemodynamic conditions,
      continuous intravenous administration of nitroglycerin could not prevent
      deterioration in gastric microvascular perfusion and microvascular haemoglobin
      saturation during gastric tube reconstruction.

PMID- 16970805
TI  - Factors influencing general practitioner referral of patients developing end
      stage renal failure: a standardised case-analysis study.
AB  - BACKGROUND: To understand why treatment referral rates for ESRF are lower in
      Ireland than in other European countries, an investigation of factors influencing
      general practitioner referral of patients developing ESRF was conducted. METHOD:
      Randomly selected general practitioners (N = 51) were interviewed using 32
      standardised written patient scenarios to elicit referral strategies. MAIN
      OUTCOME MEASURES: General practitioner referral levels and thresholds for
      patients developing end-stage renal disease; referral routes (nephrologist vs
      other physicians); influence of patient age, marital status and co-morbidity on
      referral. RESULTS: Referral levels varied widely with the full range of cases (0
      32; median = 15) referred by different doctors after consideration of first
      laboratory results. Less than half (44%) of cases were referred to a
      nephrologist. Patient age (40 vs 70 years), marital status, co-morbidity (none vs
      rheumatoid arthritis) and general practitioner prior specialist renal training
      (yes or no) did not influence referral rates. Many patients were not referred to
      a specialist at creatinine levels of 129 micromol/l (47% not referred) or 250
      micromol/l (45%). While all patients were referred at higher levels (350 and 480
      micromol/l), referral to a nephrologist decreased in likelihood as scenarios
      became more complex; 28% at 129 micromol/l creatinine; 28% at 250 micromol/l; 18%
      at 350 micromol/l and 14% at 480 micromol/l. Referral levels and routes were not
      influenced by general practitioner age, sex or practice location. Most general
      practitioners had little current contact with chronic renal patients (mean number
      in practice = 0.7, s.d. = 1.3). CONCLUSION: The very divergent management
      patterns identified highlight the need for guidance to general practitioners on
      appropriate management of this serious condition.

PMID- 16970806
TI  - Anthropometry measures and prevalence of obesity in the urban adult population of
      Cameroon: an update from the Cameroon Burden of Diabetes Baseline Survey.
AB  - BACKGROUND: The objective of the study was to provide baseline and reference data
      on the prevalence and distribution of overweight and obesity, using different
      anthropometric measurements in adult urban populations in Cameroon. METHODS: The
      Cameroon Burden of Diabetes Baseline Survey was a cross-sectional study,
      conducted in 4 urban districts (Yaounde, Douala, Garoua and Bamenda) of Cameroon,
      using the WHO Step approach for population-based assessment of cardiovascular
      risk factors. Body mass index, waist circumference and waist-to-hip ratio were
      measured using standardized methods. Overall, 10,011 individuals, 6,004 women and
      4,007 men, from 4,189 households, aged 15 years and above participated. RESULTS:
      Based on body mass index, more than 25% of urban men and almost half of urban
      women were either overweight or obese with 6.5% of men and 19.5% of women being
      obese. The prevalence of obesity showed considerable variation with age in both
      genders. Using body mass index provided the highest prevalence of obesity in men
      (6.5%) and waist-to-hip ratio the lowest prevalence (3.2%). Among women, using
      waist-to-hip ratio and waist circumference yielded the highest prevalence of
      obesity (28%) and body mass index the lowest (19.5%). There was a trend towards
      an increase in age-adjusted odd ratios of being overweight or obese with duration
      of education in both sexes. CONCLUSION: The study provides current data on
      anthropometric measurements and obesity in urban Cameroonian populations, and
      found high prevalences of overweight and obesity particularly over 35 years of
      age, and among women. Prevalence varied according to the measure used. Our
      findings highlight the need to carry out further studies in Cameroonian and other
      Sub-Saharan African populations to provide appropriate cut-off points for the
      identification of people at risk of obesity-related disorders, and indicate the
      need to implement interventions to reverse increasing levels of obesity.

PMID- 16970807
TI  - Ethnic minorities and prescription medication; concordance between self-reports
      and medical records.
AB  - BACKGROUND: Ethnic differences in health care utilisation are frequently reported
      in research. Little is known about the concordance between different methods of
      data collection among ethnic minorities. The aim of this study was to examine to
      which extent ethnic differences between self-reported data and data based on
      electronic medical records (EMR) from general practitioners (GPs) might be a
      validity issue or reflect a lower compliance among minority groups. METHODS: A
      cross-sectional, national representative general practice study, using EMR data
      from 195 GPs. The study population consisted of Dutch, Turks, Surinamese,
      Antilleans and Morrocans. Self-reported data were collected through face-to-face
      interviews and could be linked to the EMR of GPs. The main outcome measures were
      the level of agreement between annual prescribing rate based on the EMRs of GPs
      and the self-reported receipt and use of prescriptions during the preceding 14
      days. RESULTS: The pattern of ethnic differences in receipt and use of
      prescription medication depended on whether self-reported data or EMR data were
      used. Ethnic differences based on self-reports were not consistently reflected in
      EMR data. The percentage of agreement above chance between EMR data and self
      reported receipt was in general relative low. CONCLUSION: Ethnic differences
      between self-reported data and EMR data might not be fully perceived as a cross
      cultural validity issue. At least for Moroccans and Turks, compliance with the
      prescribed medication by the GP is suggested not to be optimal.

PMID- 16970808
TI  - Physician-estimated disease severity in patients with chronic heart or lung
      disease: a cross-sectional analysis.
AB  - BACKGROUND: We evaluated how well physicians' global estimates of disease
      severity correspond to more specific physician-rated disease variables as well as
      patients' self-rated health and other patient variables. METHODS: We analyzed
      baseline data from 1662 primary care patients with chronic cardiac or pulmonary
      disease who were enrolled in a longitudinal study of health-related quality of
      life (HRQoL). Each patient's primary physician rated overall disease severity,
      estimated the two-year risk of hospitalization and mortality, and reported the
      use of disease-specific medications, tests, and subspecialty referrals. Patient
      variables included sociodemographic characteristics, psychosocial factors, self
      rated health, and both generic and disease-specific HRQoL. RESULTS: Physicians
      rated 40% of their patients "about average", 30% "worse", and 30% "better" than
      the typical patient seen with the specific target disorder. The physician's
      global estimate of disease severity was strongly associated (P < 0.001) with each
      of the five more specific elements of physician-rated disease severity, but only
      marginally associated with patient self-rated health. Multivariable regression
      identified a set of patient variables that explained 16.4% of the variance in
      physician-rated disease severity. CONCLUSION: Physicians' global ratings may
      provide disease severity and prognostic information unique from and complementary
      to patient self-rated health and HRQoL measures. The elements influencing
      physician-rated disease severity and its predictive validity for clinical
      outcomes warrant prospective investigation.

PMID- 16970809
TI  - Risk factors for asthma and allergy associated with urban migration: background
      and methodology of a cross-sectional study in Afro-Ecuadorian school children in
      Northeastern Ecuador (Esmeraldas-SCAALA Study).
AB  - BACKGROUND: Asthma and allergic diseases are becoming increasingly frequent in
      children in urban centres of Latin America although the prevalence of allergic
      disease is still low in rural areas. Understanding better why the prevalence of
      asthma is greater in urban migrant populations and the role of risk factors such
      as life style and environmental exposures, may be key to understand what is
      behind this trend. METHODS/DESIGN: The Esmeraldas-SCAALA (Social Changes, Asthma
      and Allergy in Latin America) study consists of cross-sectional and nested case
      control studies of school children in rural and urban areas of Esmeraldas
      Province in Ecuador. The cross-sectional study will investigate risk factors for
      atopy and allergic disease in rural and migrant urban Afro-Ecuadorian school
      children and the nested case-control study will examine environmental, biologic
      and social risk factors for asthma among asthma cases and non-asthmatic controls
      from the cross-sectional study. Data will be collected through standardised
      questionnaires, skin prick testing to relevant aeroallergen extracts, stool
      examinations for parasites, blood sampling (for measurement of IgE, interleukins
      and other immunological parameters), anthropometric measurements for assessment
      of nutritional status, exercise testing for assessment of exercise-induced
      bronchospasm and dust sampling for measurement of household endotoxin and
      allergen levels. DISCUSSION: The information will be used to identify the factors
      associated with an increased risk of asthma and allergies in migrant and
      urbanizing populations, to improve the understanding of the causes of the
      increase in asthma prevalence and to identify potentially modifiable factors to
      inform the design of prevention programmes to reduce the risk of allergy in urban
      populations in Latin America.

PMID- 16970810
TI  - Diverse bacterial genomes encode an operon of two genes, one of which is an
      unusual class-I release factor that potentially recognizes atypical mRNA signals
      other than normal stop codons.
AB  - BACKGROUND: While all codons that specify amino acids are universally recognized
      by tRNA molecules, codons signaling termination of translation are recognized by
      proteins known as class-I release factors (RF). In most eukaryotes and archaea a
      single RF accomplishes termination at all three stop codons. In most bacteria,
      there are two RFs with overlapping specificity, RF1 recognizes UA(A/G) and RF2
      recognizes U(A/G)A. THE HYPOTHESIS: First, we hypothesize that orthologues of the
      E. coli K12 pseudogene prfH encode a third class-I RF that we designate RFH.
      Second, it is likely that RFH responds to signals other than conventional stop
      codons. Supporting evidence comes from the following facts: (i) A number of
      bacterial genomes contain prfH orthologues with no discernable interruptions in
      their ORFs. (ii) RFH shares strong sequence similarity with other class-I
      bacterial RFs. (iii) RFH contains a highly conserved GGQ motif associated with
      peptidyl hydrolysis activity (iv) residues located in the areas supposedly
      interacting with mRNA and the ribosomal decoding center are highly conserved in
      RFH, but different from other RFs. RFH lacks the functional, but non-essential
      domain 1. Yet, RFH-encoding genes are invariably accompanied by a highly
      conserved gene of unknown function, which is absent in genomes that lack a gene
      for RFH. The accompanying gene is always located upstream of the RFH gene and
      with the same orientation. The proximity of the 3' end of the former with the 5'
      end of the RFH gene makes it likely that their expression is co-regulated via
      translational coupling. In summary, RFH has the characteristics expected for a
      class-I RF, but likely with different specificity than RF1 and RF2. TESTING THE
      HYPOTHESIS: The most puzzling question is which signals RFH recognizes to trigger
      its release function. Genetic swapping of RFH mRNA recognition components with
      its RF1 or RF2 counterparts may reveal the nature of RFH signals. IMPLICATIONS OF
      THE HYPOTHESIS: The hypothesis implies a greater versatility of release-factor
      like activity in the ribosomal A-site than previously appreciated. A closer study
      of RFH may provide insight into the evolution of the genetic code and of the
      translational machinery responsible for termination of translation. REVIEWERS:
      This article was reviewed by Daniel Wilson (nominated by Eugene Koonin), Warren
      Tate (nominated by Eugene Koonin), Yoshikazu Nakamura (nominated by Eugene
      Koonin) and Eugene Koonin.

PMID- 16970811
TI  - Demographic, risk behaviour and personal network variables associated with
      prevalent hepatitis C, hepatitis B, and HIV infection in injection drug users in
      Winnipeg, Canada.
AB  - BACKGROUND: Previous studies have used social network variables to improve our
      understanding of HIV transmission. Similar analytic approaches have not been
      undertaken for hepatitis C (HCV) or B (HBV), nor used to conduct comparative
      studies on these pathogens within a single setting. METHODS: A cross-sectional
      survey consisting of a questionnaire and blood sample was conducted on injection
      drug users in Winnipeg between December 2003 and September 2004. Logistic
      regression analyses were used to correlate respondent and personal network data
      with HCV, HBV and HIV prevalence. RESULTS: At the multivariate level, pathogen
      prevalence was correlated with both respondent and IDU risk network variables.
      Pathogen transmission was associated with several distinct types of high-risk
      networks formed around specific venues (shooting galleries, hotels) or within
      users who are linked by their drug use preferences. Smaller, isolated pockets of
      IDUs also appear to exist within the larger population where behavioural patterns
      pose a lesser risk, unless or until, a given pathogen enters those networks.
      CONCLUSION: The findings suggest that consideration of both respondent and
      personal network variables can assist in understanding the transmission patterns
      of HCV, HBV, and HIV. It is important to assess these effects for multiple
      pathogens within one setting as the associations identified and the direction of
      those associations can differ between pathogens.

PMID- 16970812
TI  - Segment-specific association between cervical pillar hyperplasia (CPH) and
      degenerative joint disease (DJD).
AB  - BACKGROUND: Cervical pillar hyperplasia (CPH) is a recently described phenomenon
      of unknown etiology and clinical significance. Global assessment of pillar
      hyperplasia of the cervical spine as a unit has not shown a relationship with
      degenerative joint disease, but a more sensible explanation of the architectural
      influence of CPH on cervical spine biomechanics may be segment-specific.
      OBJECTIVE: The objective of this study was to determine the level of association
      between degenerative joint disease (DJD) and cervical pillar hyperplasia (CPH) in
      an age- and gender-matched sample on a [cervical spine] by-level basis. RESEARCH
      METHODS: Two-hundred and forty radiographs were collected from subjects ranging
      in age between 40 and 69 years. The two primary outcome measures used in the
      study were the segmental presence/absence of cervical pillar hyperplasia from C3
      to C6, and segment-specific presence/absence of degenerative joint disease from
      C1 to C7. Contingency Coefficients, at the 5% level of significance, at each
      level, were used to determine the strength of the association between CPH and
      DJD. Odds Ratios (OR) with their 95% Confidence Intervals (95% CI) were also
      calculated at each level to assess the strength of the association. RESULTS: Our
      study suggests that an approximately two-to-one odds, or a weak-to-moderate
      correlation, exists at C4 and C5 CPH and adjacent level degenerative disc disease
      (DDD); with the strongest (overall) associations demonstrated between C4 CPH and
      C4-5 DDD and between C5 CPH and C5-6 DDD. Age-stratified results demonstrated a
      similar pattern of association, even reaching the initially hypothesized OR >or=
      5.0 (95% CI > 1.0) or "moderately-strong correlation of C >or= .4 (p <or= .05)"
      in some age categories, including the 40-44, 50-59, and 60-64 years of age
      subgroups; these ORs were as follows: OR = 5.5 (95% CI 1.39-21.59); OR = 6.7 (95%
      CI 1.65-27.34); and OR = 5.3 (95% CI 1.35-21.14), respectively. CONCLUSION: Our
      results suggest that CPH has around two-to-one odds, that is, only a weak-to
      moderate association with the presence of DJD (DDD component) at specific
      cervical spine levels; therefore, CPH may be but one of several factors that
      contributes (to a clinically important degree) to the development of DJD at
      specific levels in the cervical spine.

PMID- 16970813
TI  - Predictors of colorectal cancer screening in diverse primary care practices.
AB  - BACKGROUND: To explain why rates of colorectal cancer (CRC) screening including
      fecal occult blood testing (FOBT), flexible sigmoidoscopy (FS), colonoscopy (CS),
      and barium enema (BE), are low, this study assessed determinants of CRC screening
      from medical records. METHODS: Data were abstracted from patients aged > or =64
      years selected from each clinician from 30 diverse primary care practices (n =
      981). Measurements included the rates of annual FOBT, ever receiving FOBT, ever
      receiving FS/CS/BE under a combination variable, endoscopy/barium enema (EBE).
      RESULTS: Over five years, 8% had received annual FOBT, 53% had ever received FOBT
      and 22% had ever received EBE. Annual FOBT was negatively associated with female
      gender, odds ratio (OR) = .23; 95% confidence interval = .12-.44 and positively
      associated with routinely receiving influenza vaccine, OR = 2.55 (1.45-4.47); and
      more office visits: 3 to <5 visits/year, OR = 2.78 (1.41-5.51), and > or =5
      visits/year, OR = 3.35 (1.52-7.42). Ever receiving EBE was negatively associated
      with age > or =75 years, OR = .66 (.46-.95); being widowed, OR = .59 (.38-.92);
      and positively associated with more office visits: 3 to <5 visits/year, OR = 1.83
      (1.18-2.82) and > or =5 visits/year, OR = 2.01 (1.14-3.55). CONCLUSION: Overall
      CRC screening rates were low, but were related to the number of primary care
      office visits. FOBT was related to immunization status, suggesting the possible
      benefit of linking these preventive services.

PMID- 16970814
TI  - Effects of tamoxifen on vaginal blood flow and epithelial morphology in the rat.
AB  - BACKGROUND: Tamoxifen, a selective estrogen receptor modulator with both
      estrogenic and anti-estrogenic activity, is widely used as adjuvant therapy in
      breast cancer patients. Treatment with tamoxifen is associated with sexual side
      effects, such as increased vaginal dryness and pain/discomfort during sexual
      activity. There have been limited investigations of the effect of tamoxifen on
      estrogen-dependent peripheral genital arousal responses. The objective of this
      study was to investigate the effects of tamoxifen on vaginal physiology in the
      rat. METHODS: Female Sprague-Dawley rats were subjected to sham surgery or
      bilateral ovariectomy. After 2 weeks, sham-operated rats were implanted with
      subcutaneous osmotic infusion pumps containing vehicle (control) or tamoxifen
      (150 microg/day). Ovariectomized rats were similarly infused with vehicle. After
      an additional 2 weeks, vaginal blood flow responses to pelvic nerve stimulation
      were measured by laser Doppler flowmetry and vaginal tissue was collected for
      histological and biochemical assay. RESULTS: Tamoxifen treatment did not change
      plasma estradiol concentrations relative to control animals, while ovariectomized
      rats exhibited a 60% decrease in plasma estradiol. Tamoxifen treatment caused a
      significant decrease in mean uterine weight, but did not alter mean vaginal
      weight. Vaginal blood flow was significantly decreased in tamoxifen-infused rats
      compared to controls. Similar to ovariectomized animals, estrogen receptor
      binding was increased and arginase enzyme activity was decreased in tamoxifen
      infused rats. However, different from control and ovariectomized animals, the
      vaginal epithelium in tamoxifen-infused rats appeared highly mucified. Periodic
      acid-Schiff staining confirmed a greater production of carbohydrate-rich
      compounds (e.g. mucin, glycogen) by the vaginal epithelium of tamoxifen-infused
      rats. CONCLUSION: The observations suggest that tamoxifen exerts both anti
      estrogenic and pro-estrogenic effects in the vagina. These physiological
      alterations may eventually lead to vaginal atrophy and compromise sexual
      function.

PMID- 16970815
TI  - The uvrA, uvrB and uvrC genes are required for repair of ultraviolet light
      induced DNA photoproducts in Halobacterium sp. NRC-1.
AB  - BACKGROUND: Sequenced archaeal genomes contain a variety of bacterial and
      eukaryotic DNA repair gene homologs, but relatively little is known about how
      these microorganisms actually perform DNA repair. At least some archaea,
      including the extreme halophile Halobacterium sp. NRC-1, are able to repair
      ultraviolet light (UV) induced DNA damage in the absence of light-dependent
      photoreactivation but this 'dark' repair capacity remains largely
      uncharacterized. Halobacterium sp. NRC-1 possesses homologs of the bacterial
      uvrA, uvrB, and uvrC nucleotide excision repair genes as well as several
      eukaryotic repair genes and it has been thought that multiple DNA repair pathways
      may account for the high UV resistance and dark repair capacity of this model
      halophilic archaeon. We have carried out a functional analysis, measuring repair
      capability in uvrA, uvrB and uvrC deletion mutants. RESULTS: Deletion mutants
      lacking functional uvrA, uvrB or uvrC genes, including a uvrA uvrC double mutant,
      are hypersensitive to UV and are unable to remove cyclobutane pyrimidine dimers
      or 6-4 photoproducts from their DNA after irradiation with 150 J/m2 of 254 nm UV
      C. The UV sensitivity of the uvr mutants is greatly attenuated following
      incubation under visible light, emphasizing that photoreactivation is highly
      efficient in this organism. Phylogenetic analysis of the Halobacterium uvr genes
      indicates a complex ancestry. CONCLUSION: Our results demonstrate that homologs
      of the bacterial nucleotide excision repair genes uvrA, uvrB, and uvrC are
      required for the removal of UV damage in the absence of photoreactivating light
      in Halobacterium sp. NRC-1. Deletion of these genes renders cells hypersensitive
      to UV and abolishes their ability to remove cyclobutane pyrimidine dimers and 6-4
      photoproducts in the absence of photoreactivating light. In spite of this
      inability to repair UV damaged DNA, uvrA, uvrB and uvrC deletion mutants are
      substantially less UV sensitive than excision repair mutants of E. coli or yeast.
      This may be due to efficient damage tolerance mechanisms such as recombinational
      lesion bypass, bypass DNA polymerase(s) and the existence of multiple genomes in
      Halobacterium. Phylogenetic analysis provides no clear evidence for lateral
      transfer of these genes from bacteria to archaea.

PMID- 16970816
TI  - Characterization of the aldo-keto reductase 1C gene cluster on pig chromosome 10:
      possible associations with reproductive traits.
AB  - BACKGROUND: The rate of pubertal development and weaning to estrus interval are
      correlated and affect reproductive efficiency of swine. Quantitative trait loci
      (QTL) for age of puberty, nipple number and ovulation rate have been identified
      in Meishan crosses on pig chromosome 10q (SSC10) near the telomere, which is
      homologous to human chromosome 10p15 and contains an aldo-keto reductase (AKR)
      gene cluster with at least six family members. AKRs are tissue-specific
      hydroxysteroid dehydrogenases that interconvert weak steroid hormones to their
      more potent counterparts and regulate processes involved in development,
      homeostasis and reproduction. Because of their location in the swine genome and
      their implication in reproductive physiology, this gene cluster was characterized
      and evaluated for effects on reproductive traits in swine. RESULTS: Screening the
      porcine CHORI-242 BAC library with a full-length AKR1C4 cDNA identified 7
      positive clones and sample sequencing of 5 BAC clones revealed 5 distinct AKR1C
      genes (AKR1CL2 and AKR1C1 through 4), which mapped to 126-128 cM on SSC10. Using
      the IMpRH7000rad and IMNpRH212000rad radiation hybrid panels, these 5 genes
      mapped between microsatellite markers SWR67 and SW2067. Comparison of sequence
      data with the porcine BAC fingerprint map show that the cluster of genes resides
      in a 300 kb region. Twelve SNPs were genotyped in gilts observed for age at first
      estrus and ovulation rate from the F8 and F10 generations of one-quarter Meishan
      descendants of the USMARC resource population. Age at puberty, nipple number and
      ovulation rate data were analyzed for association with genotypes by MTDFREML
      using an animal model. One SNP, a phenylalanine to isoleucine substitution in
      AKR1C2, was associated with age of puberty (p = 0.07) and possibly ovulation rate
      (p = 0.102). Two SNP in AKR1C4 were significantly associated with nipple number
      (p </= 0.03) and another possibly associated with age at puberty (p = 0.09).
      CONCLUSION: AKR1C genotypes were associated with nipple number as well as
      possible effects on age at puberty and ovulation rate. The estimated effects of
      AKR1C genotypes on these traits suggest that the SNPs are in incomplete linkage
      disequilibrium with the causal mutations that affect reproductive traits in
      swine. Further investigations are necessary to identify these mutations and
      understand how these AKR1C genes affect these important reproductive traits. The
      nucleotide sequence data reported have been submitted to GenBank and assigned
      accession numbers [GenBank:DQ474064-DQ474068, GenBank:DQ494488-DQ494490 and
      GenBank:DQ487182-DQ487184].

PMID- 16970817
TI  - Changes in aortic blood flow induced by passive leg raising predict fluid
      responsiveness in critically ill patients.
AB  - INTRODUCTION: Esophageal Doppler provides a continuous and non-invasive estimate
      of descending aortic blood flow (ABF) and corrected left ventricular ejection
      time (LVETc). Considering passive leg raising (PLR) as a reversible volume
      expansion (VE), we compared the relative abilities of PLR-induced ABF variations,
      LVETc and respiratory pulsed pressure variations (DeltaPP) to predict fluid
      responsiveness. METHODS: We studied 22 critically ill patients in acute
      circulatory failure in the supine position, during PLR, back to the supine
      position and after two consecutive VEs of 250 ml of saline. Responders were
      defined by an increase in ABF induced by 500 ml VE of more than 15%. RESULTS: Ten
      patients were responders and 12 were non-responders. In responders, the increase
      in ABF induced by PLR was similar to that induced by a 250 ml VE (16% versus 20%;
      p = 0.15). A PLR-induced increase in ABF of more than 8% predicted fluid
      responsiveness with a sensitivity of 90% and a specificity of 83%. Corresponding
      positive and negative predictive values (PPV and NPV, respectively) were 82% and
      91%, respectively. A DeltaPP threshold value of 12% predicted fluid
      responsiveness with a sensitivity of 70% and a specificity of 92%. Corresponding
      PPV and NPV were 87% and 78%, respectively. A LVETc of 245 ms or less predicted
      fluid responsiveness with a sensitivity of 70%, and a specificity of 67%.
      Corresponding PPV and NPV were 60% and 66%, respectively. CONCLUSION: The PLR
      induced increase in ABF and a DeltaPP of more than 12% offer similar predictive
      values in predicting fluid responsiveness. An isolated basal LVETc value is not a
      reliable criterion for predicting response to fluid loading.

PMID- 16970818
TI  - Ambulatory measurement of knee motion and physical activity: preliminary
      evaluation of a smart activity monitor.
AB  - BACKGROUND: There is currently a paucity of devices available for continuous,
      long-term monitoring of human joint motion. Non-invasive, inexpensive devices
      capable of recording human activity and joint motion have many applications for
      medical research. Such a device could be used to quantify range of motion outside
      the gait laboratory. The purpose of this study was to test the accuracy of the
      modified Intelligent Device for Energy Expenditure and Activity (IDEEA) in
      measuring knee flexion angles, to detect different physical activities, and to
      quantify how often healthy subjects use deep knee flexion in the ambulatory
      setting. METHODS: We compared Biomotion Laboratory (BML) "gold standard" data to
      simultaneous IDEEA measures of knee motion and gait, step up/down, and stair
      descent in 5 healthy subjects. In addition, we used a series of choreographed
      physical activities outside the BML to confirm the IDEEA's ability to accurately
      measure 7 commonly-performed physical activities. Subjects then continued data
      collection during ordinary activities outside the gait laboratory. RESULTS:
      Pooled correlations between the BML and IDEEA knee flexion angles were .97 +/-
      .03 for step up/down, .98 +/- .02 for stair descent, and .98 +/- .01 for gait. In
      the BML protocol, the IDEEA accurately identified gait, but was less accurate in
      identifying step up/down and stair descent. During sampling outside the BML, the
      IDEEA accurately detected walking, running, stair ascent, stair descent,
      standing, lying, and sitting. On average, subjects flexed their knees >120
      degrees for 0.17% of their data collection periods outside the BML. CONCLUSION:
      The modified IDEEA system is a useful clinical tool for evaluating knee motion
      and multiple physical activities in the ambulatory setting. These five healthy
      subjects rarely flexed their knees >120 degrees.

PMID- 16970820
TI  - Error in statistical tests of error in statistical tests.
AB  - BACKGROUND: A recent paper found that terminal digits of statistical values in
      Nature deviated significantly from an equiprobable distribution, indicating
      errors or inconsistencies in rounding. This finding, as well as the discovery
      that a large percentage of p values were inconsistent with reported test
      statistics, led to a great deal of concern in the popular press and scientific
      community. The findings ultimately led to new guidelines for all Nature Research
      Journals. METHODS: We checked the statistical analysis behind the original
      paper's tests of equiprobability. RESULTS: The original paper tested
      equiprobability with the Kolmogorov-Smirnov test outside its regime of validity.
      Correct tests find no statistically significant deviations from equiprobability
      for the statistical values in Nature. CONCLUSION: Statistical tests should be
      used correctly.

PMID- 16970821
TI  - Data processing and classification analysis of proteomic changes: a case study of
      oil pollution in the mussel, Mytilus edulis.
AB  - BACKGROUND: Proteomics may help to detect subtle pollution-related changes, such
      as responses to mixture pollution at low concentrations, where clear signs of
      toxicity are absent. The challenges associated with the analysis of large-scale
      multivariate proteomic datasets have been widely discussed in medical research
      and biomarker discovery. This concept has been introduced to ecotoxicology only
      recently, so data processing and classification analysis need to be refined
      before they can be readily applied in biomarker discovery and monitoring studies.
      RESULTS: Data sets obtained from a case study of oil pollution in the Blue mussel
      were investigated for differential protein expression by retentate chromatography
      mass spectrometry and decision tree classification. Different tissues and
      different settings were used to evaluate classifiers towards their discriminatory
      power. It was found that, due the intrinsic variability of the data sets,
      reliable classification of unknown samples could only be achieved on a broad
      statistical basis (n > 60) with the observed expression changes comprising high
      statistical significance and sufficient amplitude. The application of stringent
      criteria to guard against overfitting of the models eventually allowed
      satisfactory classification for only one of the investigated data sets and
      settings. CONCLUSION: Machine learning techniques provide a promising approach to
      process and extract informative expression signatures from high-dimensional mass
      spectrometry data. Even though characterisation of the proteins forming the
      expression signatures would be ideal, knowledge of the specific proteins is not
      mandatory for effective class discrimination. This may constitute a new biomarker
      approach in ecotoxicology, where working with organisms, which do not have
      sequenced genomes render protein identification by database searching
      problematic. However, data processing has to be critically evaluated and
      statistical constraints have to be considered before supervised classification
      algorithms are employed.

PMID- 16970822
TI  - What do you do for a living? Toward a more succinct definition of health services
      research.
AB  - This commentary discusses the need for, and the advantages of, a more concise,
      revised definition of the field of health services research. It argues for a
      definition that includes not only the topics on which health services research
      focuses but also the goals of health services research. A number of condensed
      definitions are provided for consideration.

PMID- 16970823
TI  - Developing and testing an instrument for identifying performance incentives in
      the Greek health care sector.
AB  - BACKGROUND: In the era of cost containment, managers are constantly pursuing
      increased organizational performance and productivity by aiming at the obvious
      target, i.e. the workforce. The health care sector, in which production processes
      are more complicated compared to other industries, is not an exception. In light
      of recent legislation in Greece in which efficiency improvement and achievement
      of specific performance targets are identified as undisputable health system
      goals, the purpose of this study was to develop a reliable and valid instrument
      for investigating the attitudes of Greek physicians, nurses and administrative
      personnel towards job-related aspects, and the extent to which these motivate
      them to improve performance and increase productivity. METHODS: A methodological
      exploratory design was employed in three phases: a) content development and
      assessment, which resulted in a 28-item instrument, b) pilot testing (N = 74) and
      c) field testing (N = 353). Internal consistency reliability was tested via
      Cronbach's alpha coefficient and factor analysis was used to identify the
      underlying constructs. Tests of scaling assumptions, according to the Multitrait
      Multimethod Matrix, were used to confirm the hypothesized component structure.
      RESULTS: Four components, referring to intrinsic individual needs and external
      job-related aspects, were revealed and explain 59.61% of the variability. They
      were subsequently labeled: job attributes, remuneration, co-workers and
      achievement. Nine items not meeting item-scale criteria were removed, resulting
      in a 19-item instrument. Scale reliability ranged from 0.782 to 0.901 and
      internal item consistency and discriminant validity criteria were satisfied.
      CONCLUSION: Overall, the instrument appears to be a promising tool for hospital
      administrations in their attempt to identify job-related factors, which motivate
      their employees. The psychometric properties were good and warrant administration
      to a larger sample of employees in the Greek healthcare system.

PMID- 16970824
TI  - Malaria hotspot areas in a highland Kenya site are consistent in epidemic and non
      epidemic years and are associated with ecological factors.
AB  - BACKGROUND: Malaria epidemics in highland areas of East Africa have caused
      considerable morbidity and mortality in the past two decades. Knowledge of
      "hotspot" areas of high malaria incidence would allow for focused preventive
      interventions in resource-poor areas, particularly if the hotspot areas can be
      discerned during non-epidemic periods and predicted by ecological factors.
      METHODS: To address this issue, spatial distribution of malaria incidence and the
      relationship of ecological factors to malaria incidence were assessed in the
      highland area of Kipsamoite, Kenya, from 2001-2004. RESULTS: Clustering of
      disease in a single geographic "hotspot" area occurred in epidemic and non
      epidemic years, with a 2.6 to 3.2-fold increased risk of malaria inside the
      hotspot, as compared to outside the area (P < 0.001, all 4 years). Altitude and
      proximity to the forest were independently associated with increased malaria risk
      in all years, including epidemic and non-epidemic years. CONCLUSION: In this
      highland area, areas of high malaria risk are consistent in epidemic and non
      epidemic years and are associated with specific ecological risk factors. Ongoing
      interventions in areas of ecological risk factors could be a cost-effective
      method of significantly reducing malaria incidence and blunting or preventing
      epidemics, even in the absence of malaria early warning systems. Further studies
      should be conducted to see if these findings hold true in varied highland
      settings.

PMID- 16970825
TI  - Semiparametric approach to characterize unique gene expression trajectories
      across time.
AB  - BACKGROUND: A semiparametric approach was used to identify groups of cDNAs and
      genes with distinct expression profiles across time and overcome the limitations
      of clustering to identify groups. The semiparametric approach allows the
      generalization of mixtures of distributions while making no specific parametric
      assumptions about the distribution of the hidden heterogeneity of the cDNAs. The
      semiparametric approach was applied to study gene expression in the brains of
      Apis mellifera ligustica honey bees raised in two colonies (A. m. mellifera and
      ligustica) with consistent patterns across five maturation ages. RESULTS: The
      semiparametric approach provided unambiguous criteria to detect groups of genes,
      trajectories and probability of gene membership to groups. The semiparametric
      results were cross-validated in both colony data sets. Gene Ontology analysis
      enhanced by genome annotation helped to confirm the semiparametric results and
      revealed that most genes with similar or related neurobiological function were
      assigned to the same group or groups with similar trajectories. Ten groups of
      genes were identified and nine groups had highly similar trajectories in both
      data sets. Differences in the trajectory of the reminder group were consistent
      with reports of accelerated maturation in ligustica colonies compared to
      mellifera colonies. CONCLUSION: The combination of microarray technology, genomic
      information and semiparametric analysis provided insights into the genomic
      plasticity and gene networks linked to behavioral maturation in the honey bee.

PMID- 16970826
TI  - A first insight into the genetic diversity of Mycobacterium tuberculosis in Dar
      es Salaam, Tanzania, assessed by spoligotyping.
AB  - BACKGROUND: Tanzania has a high tuberculosis incidence, and genotyping studies of
      Mycobacterium tuberculosis in the country are necessary in order to improve our
      understanding of the epidemic. Spoligotyping is a potentially powerful genotyping
      method due to fast generation of genotyping results, high reproducibility and low
      operation costs. The recently constructed SpolDB4 database and the model-based
      program 'Spotclust' can be used to assign isolates to families, subfamilies and
      variants. The results of a study can thus be analyzed in a global context.
      RESULTS: One hundred forty-seven pulmonary isolates from consecutive tuberculosis
      patients in Dar es Salaam were spoligotyped. SpolDB4 and 'Spotclust' were used to
      assign isolates to families, subfamilies and variants. The CAS (37%), LAM (22%)
      and EAI (17%) families were the most abundant. Despite the dominance of these
      three families, diversity was high due to variation within M. tuberculosis
      families. Of the obtained spoligopatterns, 64% were previously unrecorded.
      CONCLUSION: Spoligotyping is useful to gain an overall understanding of the local
      TB epidemic. This study demonstrates that the extensive TB epidemic in Dar es
      Salaam, Tanzania is caused by a few successful M. tuberculosis families,
      dominated by the CAS family. Import of strains was a minor problem.

PMID- 16970827
TI  - Cytotoxic T cell recognition of an HIV-1 reverse transcriptase variant peptide
      incorporating the K103N drug resistance mutation.
AB  - During HIV-1 infection, cytotoxic T cell (CTL) responses exert strong selective
      pressure on the replicating virus population. Here we report evidence for T cell
      activity against the drug resistant K103N region of viral reverse transcriptase
      in three HIV-1 infected patients exposed to NNRTI antiretroviral drugs. We
      further characterize the response in one patient by ELISPOT analysis. A nine
      amino acid peptide incorporating 103N was recognized by patient T cells whereas
      the wild type was not. The RT K103N mutation is selected by the NNRTI class of
      HIV drugs. We hypothesize that, in certain individuals, CTL responses against
      103N-containing epitopes may protect against NNRTI drug resistance.
      Characterizing such responses in the context of HLA subtypes could lead to
      tailored HIV drug therapy or to the design of therapeutic vaccines.

PMID- 16970828
TI  - Impaired psychological recovery in the elderly after the Niigata-Chuetsu
      Earthquake in Japan:a population-based study.
AB  - BACKGROUND: An earthquake measuring 6.8 on the Richter scale struck the Niigata
      Chuetsu region of Japan at 5.56 P.M. on the 23rd of October, 2004. The earthquake
      was followed by sustained occurrence of numerous aftershocks, which delayed
      reconstruction of community lifelines. Even one year after the earthquake, 9,160
      people were living in temporary housing. Such a devastating earthquake and life
      after the earthquake in an unfamiliar environment should cause psychological
      distress, especially among the elderly. METHODS: Psychological distress was
      measured using the 12-item General Health Questionnaire (GHQ-12) in 2,083
      subjects (69% response rate) who were living in transient housing five months
      after the earthquake. GHQ-12 was scored using the original method, Likert scoring
      and corrected method. The subjects were asked to assess their psychological
      status before the earthquake, their psychological status at the most stressful
      time after the earthquake and their psychological status at five months after the
      earthquake. Exploratory and confirmatory factor analysis was used to reveal the
      factor structure of GHQ12. Multiple regression analysis was performed to analyze
      the relationship between various background factors and GHQ-12 score and its
      subscale. RESULTS: GHQ-12 scores were significantly elevated at the most
      stressful time and they were significantly high even at five months after the
      earthquake. Factor analysis revealed that a model consisting of two factors
      (social dysfunction and dysphoria) using corrected GHQ scoring showed a high
      level of goodness-of-fit. Multiple regression analysis revealed that age of
      subjects affected GHQ-12 scores. GHQ-12 score as well as its factor 'social
      dysfunction' scale were increased with increasing age of subjects at five months
      after the earthquake. CONCLUSION: Impaired psychological recovery was observed
      even at five months after the Niigata-Chuetsu Earthquake in the elderly. The
      elderly were more affected by matters relating to coping with daily problems.

PMID- 16970829
TI  - Expression of P2 receptors in human B cells and Epstein-Barr virus-transformed
      lymphoblastoid cell lines.
AB  - BACKGROUND: Epstein-Barr virus (EBV) infection immortalizes primary B cells in
      vitro and generates lymphoblastoid cell lines (LCLs), which are used for several
      purposes in immunological and genetic studies. Purinergic receptors, consisting
      of P2X and P2Y, are activated by extracellular nucleotides in most tissues and
      exert various physiological effects. In B cells, especially EBV-induced LCLs,
      their expression and function have not been well studied. We investigated the
      expression of P2 receptors on primary human B cells and LCLs using the
      quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method for
      revealing the gene expression profile of the P2 receptor subtypes and their
      changes during transformation. RESULTS: The mRNA transcripts of most P2 receptors
      were detected in primary B cells; the expression of P2X3 and P2X7 receptors was
      the lowest of all the P2 receptors. By contrast, LCLs expressed several dominant
      P2 receptors--P2X4, P2X5, and P2Y11--in amounts similar to those seen in B cells
      infected with EBV for 2 weeks. The amount of most P2 subtypes in LCLs or EBV
      infected B cells was lower than in normal B cells. However, the amount of P2X7
      receptor expressed in LCLs was higher. Protein expression was studied using
      Western blotting to confirm the mRNA findings for P2X1, P2X4, P2X7, P2Y1, and
      P2Y11 receptors. ATP increased the intracellular free Ca2+ concentration
      ([Ca2+]i) by enhancing the Ca2+ influx in both B cells and LCLs in a dose
      dependent manner. CONCLUSION: These findings describe P2 receptor expression
      profiles and the effects of purinergic stimuli on B cells and suggest some
      plasticity in the expression of the P2 receptor phenotype. This may help explain
      the nature and effect of P2 receptors on B cells and their role in altering the
      characteristics of LCLs.

PMID- 16970832
TI  - Validity and utility of the Japanese version of the WHO-Five Well-Being Index in
      the context of detecting suicidal ideation in elderly community residents.
AB  - OBJECTIVE: The aim of this study is to evaluate the validity and the utility of
      the Japanese version of the WHO-Five Well-Being Index (WHO-5-J) in the context of
      detecting suicidal ideation in elderly community residents. METHODS: A sample of
      696 subjects aged 70 years or over who completed a set of questionnaires was
      examined. RESULTS: Cronbach's alpha was 0.87 and Loevinger's coefficient was
      0.64. The total score was significantly correlated with the number of
      cohabitants, the number of physical illnesses, physical functioning, instrumental
      activities of daily living, and depressive symptoms. Subjects with suicidal
      ideation had significantly lower scores on the WHO-5-J. The receiver-operating
      characteristic curve analysis indicated that the scale significantly
      discriminated the subjects with suicidal ideation. When combined with the
      assessment of a lack of perceived social support (PSS), a standard cut-off
      criterion of "a total score < or = 12 or answering 0 or 1 to any of the five
      items" more appropriately identified elderly subjects with suicidal ideation:
      sensitivity = 87%, specificity = 75%, negative predictive value = 99%, and
      positive predictive value = 10%. CONCLUSIONS: In combination with PSS, the scale
      has predictive utility to detect suicidal ideation in elderly community
      residents.

PMID- 16970830
TI  - Application of protein structure alignments to iterated hidden Markov model
      protocols for structure prediction.
AB  - BACKGROUND: One of the most powerful methods for the prediction of protein
      structure from sequence information alone is the iterative construction of
      profile-type models. Because profiles are built from sequence alignments, the
      sequences included in the alignment and the method used to align them will be
      important to the sensitivity of the resulting profile. The inclusion of highly
      diverse sequences will presumably produce a more powerful profile, but distantly
      related sequences can be difficult to align accurately using only sequence
      information. Therefore, it would be expected that the use of protein structure
      alignments to improve the selection and alignment of diverse sequence homologs
      might yield improved profiles. However, the actual utility of such an approach
      has remained unclear. RESULTS: We explored several iterative protocols for the
      generation of profile hidden Markov models. These protocols were tailored to
      allow the inclusion of protein structure alignments in the process, and were used
      for large-scale creation and benchmarking of structure alignment-enhanced models.
      We found that models using structure alignments did not provide an overall
      improvement over sequence-only models for superfamily-level structure
      predictions. However, the results also revealed that the structure alignment
      enhanced models were complimentary to the sequence-only models, particularly at
      the edge of the "twilight zone". When the two sets of models were combined, they
      provided improved results over sequence-only models alone. In addition, we found
      that the beneficial effects of the structure alignment-enhanced models could not
      be realized if the structure-based alignments were replaced with sequence-based
      alignments. Our experiments with different iterative protocols for sequence-only
      models also suggested that simple protocol modifications were unable to yield
      equivalent improvements to those provided by the structure alignment-enhanced
      models. Finally, we found that models using structure alignments provided fold
      level structure assignments that were superior to those produced by sequence-only
      models. CONCLUSION: When attempting to predict the structure of remote homologs,
      we advocate a combined approach in which both traditional models and models
      incorporating structure alignments are used.

PMID- 16970835
TI  - Effect of sevoflurane on cerebral blood flow and cerebrovascular resistance at
      surgical level of anaesthesia: a transcranial Doppler study.
AB  - BACKGROUND AND OBJECTIVE: It is widely accepted that sevoflurane affects cerebral
      circulation, but there are uncertainities regarding the magnitude of its effect.
      The aim of the present work was to assess the effect of sevoflurane on the
      cerebral circulation at surgical levels of anaesthesia. METHODS: Twenty patients
      undergoing elective lumbar discectomies were investigated. Anaesthesia was
      induced with propofol and maintained with sevoflurane. The level of surgical
      anaesthesia was determined by bispectral index, the target level was 45-55.
      Transcranial Doppler (TCD) measurement was performed before induction and after
      reaching the surgical level of anaesthesia. Besides routine parameters (middle
      cerebral artery mean blood flow velocity (MCAV) and pulsatility index (PI))
      derived parameters (estimated cerebral perfusion pressure (eCPP), cerebral blood
      flow index (CBFI) and resistance area product (RAP)) were calculated by taking
      changes of mean arterial pressure also into account. RESULTS: MCAV decreased from
      54.1 +/- 13.3 to 43.7 +/- 18.5 cm s-1, P < 0.01 and PI increased from 0.79 +/-
      0.2 to 0.92 +/- 0.2, P < 0.01 after reaching the surgical level of anaesthesia.
      As a result eCPP decreased by 18.2%, CBFI by 25.5% and RAP increased by 15%
      respectively. CONCLUSIONS: Our data indicate a vasodilatory effect of sevoflurane
      at surgical level of anaesthesia on large cerebral vessels or a vasoconstriction
      of the resistance arterioles likely caused by decreased brain metabolism.

PMID- 16970836
TI  - Community-associated methicillin-resistant Staphylococcus aureus in the patient
      with HIV infection.
AB  - The prevalence of community-associated methicillin-resistant Staphylococcus
      aureus (CA-MRSA) has increased alarmingly in both the general population and the
      HIV-infected community. We look at the background of MRSA including the
      mechanisms of resistance, genetics, and trends in the individual with HIV
      infection. Numerous studies have investigated the risk factors for CA-MRSA. Other
      studies have further characterized the incidence of and risk factors for MRSA
      infections in the HIV community. Although one might not readily associate
      advanced HIV infection with increased susceptibility to bacterial pathogens, a
      number of studies have explained the mechanisms of this B-cell-mediated
      susceptibility. Invasive MRSA infections have spread into communities, are
      increasingly prevalent, and pose a public health challenge for their containment,
      prevention, and treatment.

PMID- 16970837
TI  - Nonalcoholic fatty liver disease and HIV infection.
AB  - As persons with HIV live longer, chronic liver disease is increasingly important.
      Nonalcoholic fatty liver disease (NAFLD) is characterized by excess fat in
      hepatocytes in patients without significant alcohol use. It can progress from
      steatosis to nonalcoholic steatohepatitis (NASH) to cirrhosis. Visceral obesity
      and insulin resistance are integral to the pathogenesis of NAFLD. Patients with
      HIV are at greater risk of NAFLD due to antiretroviral therapy and viral
      hepatitis coinfection. Antiretroviral therapy can lead to patterns of injury that
      include steatosis and NASH. Coinfection with hepatitis C virus increases the risk
      of insulin resistance and hepatic steatosis, and co-existent features of NASH
      have also been reported. Histological-based, longitudinal studies are needed that
      address the interactions of NAFLD and HIV infection, the effects of
      antiretroviral therapy and hepatotropic virus coinfection, and inform better
      management strategies.

PMID- 16970838
TI  - Genetic, ethnic, and gender differences in the pharmacokinetics of antiretroviral
      agents.
AB  - Variable antiretroviral therapy (ART) drug response likely reflects the combined
      influence of environment, underlying disease, concurrent drugs, and genetics.
      Gender exerts modest or negligible effects on ART disposition, and it is expected
      to have limited clinical implication, although it should be accounted for in
      large population studies. Ethnic denominations have, with the notable exception
      of efavirenz, no clear influence on ART disposition. Exploration of genetic
      factors might offer a better comprehension to the largely unpredictable and
      unresolved variability in ART concentrations and related toxicity or treatment
      outcome. Despite the negative perception of genetic research among the general
      public, this type of investigation is now widely accepted by concerned parties:
      patients, relatives, and study volunteers.

PMID- 16970839
TI  - Endothelial dysfunction in HIV infection.
AB  - Highly active antiretroviral therapy (HAART) has significantly improved the
      prognosis of patients with HIV infection; however, the use of protease inhibitors
      has been associated with increased cardiovascular events and worsening of
      multiple coronary heart disease risk factors including dyslipidemia, insulin
      resistance, and endothelial dysfunction. Endothelial dysfunction may be caused by
      the infection itself, the immunologic responses due to the HIV virus, and also by
      the effects of HAART through their effects on both lipid and glucose metabolism.
      The study of endothelial function in HIV infection and its modifications by HAART
      is an exciting new field in clinical research, limited by multiple factors such
      as viral factors, immunologic conditions, and metabolic drug effects that could
      affect the interpretation of endothelial impairment. Further studies are still
      needed to understand the significance of endothelial dysfunction in the
      cardiovascular risk assessment of patients with HIV infection.

PMID- 16970840
TI  - Solid organ transplantation is a reality for patients with HIV infection.
AB  - Recent policies, guidelines, and laws reflect promising preliminary outcomes
      among transplant recipients with HIV infection, and ethical analyses suggest that
      it is not justifiable to deny solid organ transplantation based solely on HIV
      infection status. These studies consistently describe stable HIV disease
      following liver and kidney transplantation. Despite good graft survival, kidney
      allograft rejection occurs frequently, and serious non-AIDS-defining infections
      requiring hospitalization are common following antirejection therapy. Profound
      interactions between immunosuppressants and antiretroviral drugs require careful
      monitoring, dose adjustment, and highly effective communication between the
      patient and a multidisciplinary group of health care providers. Despite these
      scientific and policy advances, many health care providers and patients remain
      unaware of ongoing progress in this field. The implications are critical, as late
      referral for liver transplant evaluation increases the pretransplant mortality
      risk. Because important patient selection and clinical management questions
      remain, it is critical that ongoing studies are completed quickly.

PMID- 16970841
TI  - Tuberculosis and HIV: Implications in the developing world.
AB  - Developing countries bear the brunt of the epidemics of AIDS and tuberculosis
      (TB), and the management of patients with both diseases poses a particular
      challenge in these settings. In this article, we review implications for the twin
      epidemics of HIV and TB for the developing world with respect to diagnosis,
      prevention, treatment and integration of national TB and HIV programs.

PMID- 16970842
TI  - Arm trajectories in dyskinetic cerebral palsy have increased random variability.
AB  - Dyskinetic cerebral palsy results from injury to the basal ganglia early in life.
      Symptoms can include hyperkinetic or dystonic arm movements that impair function.
      It is not known whether these movements comprise a small number of specific
      abnormal motor patterns or whether they are random and variable. We hypothesize
      that injury to the basal ganglia leads to impaired filtering and removal of
      undesired neural signals and that lack of appropriate removal of noisy or
      irrelevant neural signals leads to random and variable arm movements. To test
      this hypothesis, we quantified the variability in arm trajectories while seven
      children with dyskinetic cerebral palsy between the ages of 4 and 13 years old
      made repeated outward reaching movements. We compared the results with those of
      21 healthy children between the ages of 5 and 16 years. The best-fit trajectory
      to the set of reaching movements for each child was taken as the predictable
      component of movement. We calculated the ratio of the power in the best-fit
      trajectory to the total variance. This measure is the signal-to-noise ratio, and
      it quantifies the extent to which trajectories are predictable. We found that
      children with dyskinetic cerebral palsy had a significantly reduced signal-to
      noise ratio compared with healthy children at similar ages. This result shows
      that there is increased movement variability, and it is consistent with the
      hypothesis that inadequate removal of noisy signals could be a cause of the
      movement disorder in dyskinetic cerebral palsy.

PMID- 16970843
TI  - Evaluation of the influence of antiepileptic therapy on antioxidant enzyme
      activity and lipid peroxidation in erythrocytes of children with epilepsy.
AB  - The aim of this study was to evaluate the influence of antiepileptic therapy on
      antioxidant enzyme activity and lipid peroxidation in the erythrocytes of
      children with epilepsy. For this purpose, the activity of superoxide dismutase,
      glutathione peroxidase, and glutathione reductase and the malondialdehyde
      concentration in 61 healthy children and 90 children with epilepsy were measured.
      The activities of all of these enzymes were insignificantly higher, whereas the
      malondialdehyde concentration was significantly lower in the patients treated
      with carbamazepine monotherapy. In patients treated with valproate monotherapy,
      the activities of all enzymes were insignificantly lower, whereas the
      malondialdehyde concentration was insignificantly higher. In patients treated
      with polytherapy, the activity of superoxide dismutase was insignificantly lower,
      whereas the activity of glutathione peroxidase and glutathione reductase was
      insignificantly higher and the malondialdehyde concentration was lower. There
      were differences in glutathione reductase activity between the valproate
      monotherapy group and both the carbamazepine monotherapy and polytherapy groups
      and in malondialdehyde concentrations between the carbamazepine and valproate
      groups. The results indicate that the oxidant-antioxidant balance in children
      with epilepsy is modified by antiepileptic therapy.

PMID- 16970844
TI  - 14-3-3 protein detection in the cerebrospinal fluid of patients with influenza
      associated encephalopathy.
AB  - Influenza-associated encephalopathy is characterized by high fever, convulsions,
      and loss of consciousness associated with influenza infection in children, but
      its pathophysiology remains to be clarified. We examined 14-3-3 proteins, which
      are acidic brain proteins, in cerebrospinal fluid by immunoblotting in four
      patients with influenza-associated encephalopathy, four patients with influenza
      without encephalopathy, and four patients with another encephalopathy.
      Interestingly, we detected 14-3-3 proteins in all four patients with influenza
      associated encephalopathy (100%) but not in any of the other patients. 14-3-3
      isoforms, including beta, gamma, epsilon, xi, and theta, were found in the
      cerebrospinal fluid of the patients with influenza-associated encephalopathy,
      suggesting extensive damage to the brain. We conclude that 14-3-3 proteins in
      cerebrospinal fluid are highly detectable in influenza-associated encephalopathy
      and thus can be used as a rapid diagnostic marker.

PMID- 16970845
TI  - Diffusion tensor imaging of the corticospinal tract following cerebral
      hemispherectomy.
AB  - Following cerebral hemispherectomy, the corticospinal tract is believed to
      undergo reorganizational changes, which can induce enhanced function of the
      contralateral motor pathway and mediate partial recovery of motor function. The
      aim of this study was to use diffusion tensor imaging to investigate the effects
      of hemispherectomy on the corticospinal tract, with particular attention to the
      corticospinal tract contralateral to the resection. Diffusion tensor imaging
      would presumably detect microstructural abnormalities through quantitative
      measurements of the fiber tract integrity and orientation. Four patients with
      anatomic hemispherectomy and three patients with subtotal hemispherectomy were
      examined and compared with age-matched normal controls. Apparent diffusion
      coefficient and fractional anisotropy values were measured in regions along the
      corticospinal tract: internal capsule, cerebral peduncle, rostral pons, midpons,
      and caudal pons. None of the patients with anatomic hemispherectomy or subtotal
      hemispherectomy showed significant changes in either apparent diffusion
      coefficient or fractional anisotropy values in the corticospinal tract
      contralateral to the resected hemisphere, whereas increased apparent diffusion
      coefficient and decreased fractional anisotropy were observed in the ipsilateral
      rostral pons, midpons, and caudal pons of all patients with anatomic
      hemispherectomy, as well as in the ipsilateral cerebral peduncle of one patient
      with subtotal hemispherectomy. Increased apparent diffusion coefficient values
      were also noted in the ipsilateral internal capsule of the same patient. This
      study revealed no evidence of significant reinforcement of the contralateral
      corticospinal tract in patients with hemispherectomy, at least from diffusion
      tensor imaging measurements, but suggests that wallerian degeneration most likely
      occurs in the ipsilateral motor pathway.

PMID- 16970846
TI  - Congenital and compensated vestibular dysfunction in childhood: an overlooked
      entity.
AB  - We report five children with previously unrecognized vestibular dysfunction
      detected by clinical examination and confirmed by quantitative vestibular
      testing. Patient 1 presented with fluctuating visual acuity and intermittent
      nystagmus. Patient 2 had congenital hearing loss associated with imbalance,
      delayed motor development, and cyclic vomiting. Patient 3 had neurotrophic
      keratitis with an intermittent head tilt, imbalance, and motor delays. Patient 4
      showed ataxia and eye movement abnormalities following traumatic brain injury and
      had reading difficulties. Patient 5 had episodic vertigo and eye movement
      abnormalities from infancy. Clinical vestibular testing emphasized spontaneous
      nystagmus, rapid head thrust, and assessment of post-rotatory nystagmus.
      Quantitative vestibular testing included the sinusoidal chair rotation and
      velocity step tests, measurement of dynamic visual acuity, post-head-shake
      nystagmus, and computerized platform posturography. Pediatric neurologists
      encounter children with congenital and compensated vestibular dysfunction, which
      can be recognized on the basis of relevant history and clinical abnormalities of
      the ocular-ocular reflex.

PMID- 16970847
TI  - Can we define the pathogenesis of human periventricular white-matter injury using
      animal models?

PMID- 16970848
TI  - Role of instrumented fetal sheep preparations in defining the pathogenesis of
      human periventricular white-matter injury.
AB  - Periventricular white-matter injury is the major form of brain injury associated
      with prematurity and the leading cause of cerebral palsy in survivors of
      premature birth. Progress in understanding the pathogenesis of periventricular
      white-matter injury requires the development of animal models that are relevant
      to the unique physiology of the preterm human brain and that replicate the major
      neuropathologic features of human injury. The sheep is the most extensively
      studied true fetal preparation. The neurodevelopment of the preterm sheep fetus
      (0.65 gestation) is comparable to that of the preterm human between approximately
      24 and 28 weeks. The size of the fetal sheep permits chronic instrumentation so
      that well-defined insults can be studied with reliable measurements of blood flow
      and metabolism in cerebral white-matter. We review here recent developments in
      the understanding of the role of cerebral hypoxia-ischemia and vulnerable
      oligodendrocyte progenitors in the pathogenesis of periventricular white-matter
      injury in the immature sheep fetus. We focus on recent developments in high
      resolution spatially defined cerebral blood flow measurements in utero. We
      determined ovine white-matter maturation between 90 and 120 days' gestation, as
      defined by immunohistochemical localization of oligodendrocyte lineage-specific
      antibodies. There was considerable spatial and temporal heterogeneity in
      oligodendrocyte maturation in the immature periventricular white-matter.
      Oligodendrocyte maturation in the 90- to 105-day fetal sheep closely coincided
      with that of the preterm human during the high-risk period for white-matter
      injury. Hence, the immature state of the 90- to 105-day fetal periventricular
      white-matter is an optimal and dynamic developmental window to study the role of
      cellular-maturational factors in the pathogenesis of white-matter injury. We
      conclude with a review of the significant advantages of the instrumented fetal
      sheep to accelerate progress in the translation of preventive therapies for
      periventricular white-matter injury and cerebral palsy.

PMID- 16970849
TI  - Neurocysticercosis.

PMID- 16970850
TI  - Long survival following bacterial meningitis-associated brain destruction.
AB  - This report describes the brain autopsy of a boy who at age 4(1/2) years
      experienced an episode of fulminant Haemophilus influenzae type b bacterial
      meningitis, resulting in massive brain destruction and the clinical signs of
      brain death. However, medical intervention maintained him for an additional two
      decades. Subsequent autopsy revealed a calcified intracranial spherical structure
      weighing 750 g and consisting of a calcified shell containing grumous material
      and cystic spaces with no recognizable neural elements grossly or
      microscopically. This case represents an example of long survival of brain death
      with a living body.

PMID- 16970851
TI  - Mobile medical computing driven by the complexity of neurologic diagnosis.
AB  - Medical computing has been split between palm-sized computers optimized for
      mobility and desktop computers optimized for capability. This split was due to
      technology too immature to deliver both mobility and capability in the same
      computer and the lack of medical software that demanded both mobility and
      capability. Advances in hardware and software are ushering in an era in which
      fully capable computers will be available ubiquitously. As a result, medical
      practice, education and publishing will change. Medical practice will be improved
      by the use of software that not only assists with diagnosis but can do so at the
      bedside, where the doctor can act immediately upon suggestions such as useful
      findings to check. Medical education will shift away from a focus on details of
      unusual diseases and toward a focus on skills of physical examination and using
      computerized tools. Medical publishing, in contrast, will shift toward greater
      detail: it will be increasingly important to quantitate the frequency of findings
      in diseases and their time course since such information can have a major impact
      clinically when added to decision support software.

PMID- 16970852
TI  - Migration abnormality in the left cingulate gyrus presenting with autistic
      disorder.
AB  - Autism, characterized by an impairment in communication, including language,
      narrowly focused interests, and poor sociability, is a neurodevelopmental
      disorder of still largely unknown pathogenesis. In children with autistic
      symptomatology, the most consistent functional or anatomic abnormalities are
      found in the cingulate gyrus, particularly in the anterior regions. Neuronal
      migration malformations caused by incomplete neuronal migration and characterized
      by loss of the normal gyral patterns in the cerebral hemispheres and prominent
      disorganization of the cerebral cortical cytoarchitecture are generally
      associated with profound neurologic deficits, epilepsy, and autism. In this
      report, we present a case with an isolated migration abnormality located in the
      anterior part of the left cingulate gyrus who was admitted with the complaints of
      epileptic seizures and autism. In addition, the role of the localization of the
      migration abnormality in the appearance of autistic symptomatology is discussed.

PMID- 16970853
TI  - Administration of intravenous tissue plasminogen activator in a pediatric patient
      with acute ischemic stroke.
AB  - Intravenous tissue plasminogen activator is the only therapy approved by the US
      Food and Drug Administration (FDA) for the treatment of acute ischemic strokes.
      The National Institutes of Health (NIH)-sponsored study that led to the approval
      of tissue plasminogen activator to be used in acute ischemic strokes included
      only individuals 18 years of age and older. We report a case of a pediatric
      patient who suffered a dominant-hemisphere acute ischemic stroke who was treated
      with intravenous tissue plasminogen activator. Our patient's symptoms began to
      resolve 4 hours after treatment, and he had a complete recovery after 8 hours.
      The clinical outcome was excellent and without complications. Tissue plasminogen
      activator administration can be safe and effective in younger patients.
      Randomized, controlled, double-blind studies are needed.

PMID- 16970854
TI  - False-positive metaiodobenzylguanidine scan for neuroblastoma in a child with
      opsoclonus-myoclonus syndrome treated with adrenocorticotropic hormone (acth).
AB  - We describe the case of a 2-year-old girl with opsoclonus-myoclonus syndrome
      treated with chronic adrenocorticotropic hormone (ACTH) in which a
      metaiodobenzylguanidine scan showed abnormal radiotracer uptake in the left
      adrenal gland region, interpreted as the site of an occult neuroblastoma. As this
      finding was not corroborated by previous or subsequent metaiodobenzylguanidine
      scans or by computed tomography (CT) or magnetic resonance imaging (MRI), we
      attribute the finding to being a false-positive result from adrenal hyperplasia
      owing to chronic use of ACTH and not to neuroblastoma. Metaiodobenzylguanidine
      scintigraphy is an extremely important nuclear medicine examination tool used for
      the evaluation and staging of pediatric neuroblastoma. We highlight the need for
      cautious interpretation of metaiodobenzylguanidine as a screening tool for
      neuroblastoma in patients treated with ACTH.

PMID- 16970855
TI  - 99mTc-HMPAO brain perfusion single-photon emission computed tomography in
      children with Down syndrome: relationship to epilepsy, thyroid functions, and
      congenital heart disease.
AB  - In recent years, it has been possible for patients with Down syndrome to live
      longer with advanced medical treatment and social support. As a result, the
      problems of these patients, such as thyroid diseases, leukemia, and Alzheimer
      disease, would be encountered more frequently. In this study, we aimed to perform
      the brain perfusion of children with Down syndrome by technetium 99m
      hexamethylpropylene amine oxime (99mTc-HMPAO) single-photon emission computed
      tomography (SPECT) and to determine the relationship between brain perfusion and
      epilepsy, thyroid function tests, congenital heart disease, and level of mental
      and motor development. Thirty patients with Down syndrome, aged between 1 and 15
      years, were included in our study. Demographic data, the existence of epilepsy
      and congenital heart defects, the level of mental and motor development, serum
      levels of thyroid hormones, and autoantibodies were determined. All patients
      underwent computed tomography (CT) and/or magnetic resonance imaging (MRI).
      Cerebral SPECT was performed in all cases to evaluate the brain perfusion
      pattern. According to the visual evaluation of cerebral SPECT results,
      hypoperfusion was detected in 11 cases (37%). Patients with cerebral
      hypoperfusion (group 1) and patients with normal cerebral perfusion (group 2)
      were compared. There was no difference between group 1 and group 2 in terms of
      demographic data, congenital heart defects, IQ levels, thyroid hormones, and
      autoantibodies, but the incidence of epilepsy was significantly higher in group 1
      (P<.001). When motor and mental development levels were compared, it was found
      that cases in group 1 were significantly more retarded in personal-social and
      fine motor skills (P<.05). The present study showed that cerebral hypoperfusion
      in children with Down syndrome is mostly related to epilepsy and the other
      coexisting conditions, congenital heart disease and hypothyroidism. Patients with
      cerebral hypoperfusion also have more retarded developmental levels, especially
      in personal-social and fine motor skills.

PMID- 16970856
TI  - Neuroradiologic findings in Sotos syndrome.
AB  - Sotos syndrome is a well-known anomaly syndrome characterized by overgrowth,
      characteristic facial gestalt, and developmental delay, and haploinsufficiency of
      the NSD1 gene has been revealed as one of the major genetic causes. However,
      there have been only a few reports on neuroradiologic findings by computed
      tomography (CT) or magnetic resonance imaging (MRI), and functional examination
      of the brain has not been reported. We examined three cases with typical Sotos
      syndrome, which also were confirmed by genetic analysis with a specific probe for
      the NSD1 gene. The results of MRI showed the characteristic features that have
      been reported previously. The findings obtained by using single-photon emission
      computed tomography and magnetic resonance spectroscopy suggested an association
      between mental delay and behavioral tendency in Sotos syndrome and immaturity in
      frontal brain function.

PMID- 16970857
TI  - Methadone intoxication in a child: toxic encephalopathy?
AB  - Methadone is used in the treatment of opioid addiction. Acute intoxication can
      lead to severe consequences and can even be lethal. In several case reports and
      small series, a presumably toxic leukoencephalopathy is described resulting from
      inhalation of heroin. We present the case of a 3-year-old boy who ingested
      methadone accidentally. In a coma with acute obstructive hydrocephalus owing to
      massive cerebellar edema and supratentorial lesions, he was successfully treated
      with methylprednisolone and cerebrospinal fluid external drainage. To our
      knowledge, this is the first report of an encephalopathy associated with
      synthetic opioid intoxication.

PMID- 16970858
TI  - Electroencephalographic (EEG) findings in posterior reversible encephalopathy
      associated with immunosuppressants.
AB  - Posterior reversible encephalopathy has been reported in patients who receive
      immunosuppressants. Compared with radiologic studies, electroencephalographic
      (EEG) findings are not well described. We performed EEG serially in three
      children who suffered from posterior reversible encephalopathy associated with
      tacrolimus or cyclosporine. EEG showed continuous focal rhythmic activities in
      the acute period. EEG findings normalized after the clinical manifestations had
      disappeared. We conclude that EEG is useful for the diagnosis and follow-up of
      posterior reversible encephalopathy.

PMID- 16970859
TI  - Stroke associated with central nervous system vasculitis after West Nile virus
      infection.
AB  - We report the association of West Nile virus infection, isolated vasculitis, and
      stroke in a 9-year-old girl. West Nile virus is of growing epidemiologic
      importance and should be considered in the differential diagnosis of stroke
      etiologies, especially during late summer and in patients with a history of
      exposure in areas where West Nile virus transmission is present.

PMID- 16970863
TI  - Tourette syndrome: diagnosis, strategies, therapies, pathogenesis, and future
      research directions.

PMID- 16970864
TI  - Tourette syndrome: the self under siege.
AB  - Tourette syndrome is a neurodevelopmental disorder characterized by motor and
      vocal tics--rapid, repetitive, stereotyped movements or vocalizations. Tourette
      syndrome typically has a prepubertal onset, and boys are more commonly affected
      than girls. Symptoms usually begin with transient bouts of simple motor tics. By
      age 10 years, most children are aware of nearly irresistible somatosensory urges
      that precede the tics. These urges likely reflect a defect in sensorimotor gating
      because they intrude into the child's conscious awareness and become a source of
      distraction and distress. A momentary sense of relief typically follows the
      completion of a tic. Over the course of hours, tics occur in bouts, with a
      regular intertic interval. Tics increase during periods of emotional excitement
      and fatigue. Tics can become "complex" in nature and appear to be purposeful.
      Tics can be willfully suppressed for brief intervals and can be evoked by the
      mere mention of them. Tics typically diminish during periods of goal-directed
      behavior, especially those that involve both heightened attention and fine motor
      or vocal control, as occur in musical and athletic performances. Over the course
      of months, tics wax and wane. New tics appear, often in response to new sources
      of somatosensory irritation, such as the appearance of a persistent vocal tic (a
      cough) following a cold. Over the course of years, tic severity typically peaks
      between 8 and 12 years of age. By the end of the second decade of life, many
      individuals are virtually tic free. Less than 20% of cases continue to experience
      clinically impairing tics as adults. Tics rarely occur in isolation, and other
      coexisting conditions--such as behavioral disinhibition, hypersensitivity to a
      broad range of sensory stimuli, problems with visual motor integration,
      procedural learning difficulties, attention-deficit hyperactivity disorder
      (ADHD), obsessive-compulsive disorder, depression, anxiety, and emotional
      instability--are often a greater source of impairment than the tics themselves.
      Emerging behavioral treatments of Tourette syndrome are based in part on an
      understanding of the moment-to-moment experience of somatosensory urges and motor
      response. With identification of specific genes of major effect and advances in
      our understanding of the neural circuitry of sensorimotor gating, habit
      formation, and procedural memory--together with insights from postmortem brain
      studies, in vivo brain imaging, and electrophysiologic recordings--we might be on
      the threshold of a deeper understanding of the phenomenology and natural history
      of Tourette syndrome.

PMID- 16970865
TI  - Randomized trial of parent management training in children with tic disorders and
      disruptive behavior.
AB  - Oppositional, defiant, and disruptive behaviors are common in clinical samples of
      children with tic disorders. In this study, we sought to evaluate the short-term
      efficacy of a structured parent training program in children with tic disorders
      accompanied by disruptive behavior. Children with tic disorders and at least a
      moderate level of disruptive behavior were randomly assigned to a 10-session
      structured parent management training program or to continue treatment as usual.
      Twenty-four children (18 boys and 6 girls) between the ages of 6 and 12 years
      (mean 8.9 +/- 2.0 years) were enrolled; 23 subjects completed the study. At
      baseline, subjects showed moderate to severe levels of oppositional and defiant
      behavior. Twenty subjects (83%) were on stable medication. The parent-rated
      Disruptive Behavior Rating Scale score decreased by 51% in the parent management
      training group compared with a decrease of 19% in the treatment as usual group (P
      < .05). On the Improvement scale of the Clinical Global Impression, a rater
      masked to treatment assignment classified 7 of 11 subjects who completed parent
      management training as much improved or very much improved compared with 2 of 12
      subjects in the treatment as usual group (Fisher exact test, P < .05). These
      results suggest that parent management training is helpful for short-term
      improvement in disruptive behavior problems in children with tic disorders.
      Larger randomized clinical trials are needed.

PMID- 16970866
TI  - Co-occurring psychiatric disorders in children and adolescents with Tourette
      syndrome.
AB  - More than half of all children and adolescents with Tourette syndrome show
      evidence of psychiatric comorbidity, exhibiting symptoms of attention-deficit
      hyperactivity disorder (ADHD), obsessive-compulsive disorder, and other anxiety
      and mood disorders. Although the prevalence of co-occurring conditions varies
      depending on the clinical setting, it is crucial for clinicians to be familiar
      with these disorders because they are often more impairing than tics and can
      influence the initial treatment choice. Left untreated, these conditions can
      negatively affect important developmental outcomes, such as academic and social
      functioning. We review the most common co-occurring disorders, the relationship
      of these co-occurring disorders to Tourette syndrome, and treatment
      recommendations for co-occurring conditions when tic symptoms are present.

PMID- 16970867
TI  - Genetics and epidemiology of Tourette syndrome.
AB  - Although the genetic basis of Tourette syndrome is well established, uncertainty
      about how best to define and assess the Tourette syndrome phenotype has hampered
      efforts to identify the genes responsible for susceptibility to the disorder. In
      addition, such efforts have typically been underpowered or were undertaken before
      the technology was available to perform systematic genome-wide genetic
      investigations. The Tourette Syndrome Association International Consortium on
      Genetics was formed by more than a dozen research groups from around the world to
      develop common approaches to phenotyping Tourette syndrome and to pool samples
      for uniform, well-powered genetic investigations. Several recent advances,
      including the completion of genome-wide scans of affected sib-pairs and large
      families, show real promise for identifying Tourette syndrome susceptibility
      genes. In this review, we describe the key epidemiologic, linkage, and
      association studies in Tourette syndrome and illustrate the strategies currently
      being used to identify Tourette syndrome genes.

PMID- 16970868
TI  - Neuroimaging of Tourette syndrome.
AB  - Traditional neuropathologic methods have provided only limited insight into the
      central nervous system abnormalities underlying Tourette syndrome. In the past 20
      years, investigators have turned increasingly to in vivo neuroimaging approaches
      to localize, quantify, and characterize neuroanatomic, functional, and
      neurochemical distinctions in living subjects with Tourette syndrome. Research
      methods have included aggregate measures of cerebral energy metabolism,
      assessments of cerebral structure and size, and highly specific assessments of
      neurochemical markers of select neurons and synapses. Although the available data
      have important limitations, an encouraging convergence of findings implicates
      abnormal function in the Tourette syndrome striatum and in associated limbic and
      frontal cortical systems.

PMID- 16970869
TI  - Tic disorders: neural circuits, neurochemistry, and neuroimmunology.
AB  - The neuroanatomy and neurochemistry underlying tic disorders are thought to
      involve corticostriatothalamocortical circuits and dysregulation of their
      component neurotransmitter systems. Tourette syndrome is a tic disorder that
      begins in childhood and follows a waxing and waning course of tic severity.
      Although it is generally believed to have a genetic component, its etiology has
      not been fully elucidated. The clinical entity pediatric autoimmune
      neuropsychiatric disorders associated with streptococcal infection (PANDAS) has
      led some to suggest that the pathophysiology of tics in some individuals might
      involve a postinfectious autoimmune component. We review the neural circuits and
      neurochemistry of Tourette syndrome and evaluate the evidence for and against a
      role for autoimmunity in the expression of tics.

PMID- 16970870
TI  - Treatment of children and adolescents with tics and Tourette syndrome.
AB  - Tics, patterned movements distinct from stereotypies, myoclonus, and other
      hyperkinetic movements, are quite common in children, particularly among those
      with developmental and psychiatric disorders. Thus, tics can indicate the
      presence of atypical neurodevelopment or broader difficulties with cognition or
      mood. Tics are also the cardinal feature of Tourette syndrome, a childhood-onset
      neurobehavioral disorder characterized by a chronic inability to suppress or an
      urge to perform patterned, repetitive movements. Patients with Tourette syndrome
      most commonly have, in addition to tics, symptoms of inattention, hyperactivity,
      obsessiveness, or anxiety. Achieving the most effective treatment of a child with
      tics is contingent on proper diagnosis of the movement disorder and thorough
      assessment for other problems, followed by consideration of both nonpharmacologic
      and pharmacologic interventions for any and all symptoms interfering with the
      child's function and quality of life. This review focuses primarily on the
      diagnosis and medical treatment of tics in children and adolescents with Tourette
      syndrome.

PMID- 16970871
TI  - Attention-deficit hyperactivity disorder (ADHD) comorbidity: a case for "pure"
      Tourette syndrome?
AB  - More than a decade of research regarding the motoric characteristics of the
      attention-deficit hyperactivity disorder (ADHD) that accompanies Tourette
      syndrome has revealed unique anatomic and neurobehavioral differences and
      highlighted the importance of distinguishing children with this form from the 40%
      of children with Tourette syndrome who do not have ADHD. This distinction is
      important in providing guidance to parents and to patients and in formulating
      expectations for short- and long-term prognoses. In addition, study methodologies
      that fail to categorize patients in this way and instead involve covarying for
      dimensional symptoms of ADHD obscure biologically distinctive circuits and
      clinically meaningful patient characteristics.

PMID- 16970872
TI  - Obsessive-compulsive disorder in Tourette syndrome.
AB  - Several lines of evidence suggest a meaningful association between obsessive
      compulsive disorder and Tourette syndrome, including comorbidity, phenomenologic
      overlap, evidence from family and genetic studies, and the possible role of basal
      ganglia circuitry in both conditions. Obsessive-compulsive behaviors occur
      frequently in patients who have Tourette syndrome and tend to have a later onset
      than tics. Despite commonalities, the approaches to treating tics and obsessive
      compulsive symptoms are actually quite distinct. A specialized form of cognitive
      behavior therapy and pharmacotherapy with a potent serotonin reuptake inhibitor
      are the two established first-line therapies for obsessive-compulsive disorder.
      An adequate trial of a serotonin reuptake inhibitor is 10 to 12 weeks in duration
      at doses near the upper end of the recommended range for age and weight. Cases of
      obsessive-compulsive disorder that do not sufficiently improve with serotonin
      reuptake inhibitors might benefit from adjunctive low-dose antipsychotic (eg,
      risperidone) medication whether or not tics are present. Warnings about an
      increased risk of suicidality among children and adolescents taking
      antidepressants for pediatric depression extend to those taking the medications
      for obsessive-compulsive disorder, but the risk-to-benefit ratio is more
      favorable in this latter population because several serotonin reuptake inhibitors
      have been shown to be efficacious in obsessive-compulsive disorder.

PMID- 16970873
TI  - Novel surgical therapies for Tourette syndrome.
AB  - Tourette syndrome is a common neurologic disorder with close ties to obsessive
      compulsive disorder and attention-deficit hyperactivity disorder (ADHD). The
      majority of patients improve spontaneously as they near adulthood. Most others
      are effectively treated with pharmacologic agents, although these therapies fail
      for an unfortunate few. For patients debilitated by the disease despite medical
      therapy, surgery can become an important option.

PMID- 16970874
TI  - Brief review of habit reversal training for Tourette syndrome.
AB  - It is well established that Tourette syndrome has a neurobiologic origin.
      Although pharmacotherapy is the most commonly prescribed intervention, there is
      considerable evidence to support the use of behavior therapy, specifically habit
      reversal training, as an alternative or adjunct treatment for some individuals
      with Tourette syndrome. Unfortunately, many professionals are unfamiliar with
      habit reversal training. The purpose of this review is to provide readers with a
      brief review of empiric studies on habit reversal training, update readers on the
      current state and future of behavior therapy for Tourette syndrome, and provide
      resources for those readers interested in additional information.

PMID- 16970875
TI  - Autoimmune neuropsychiatric disorders associated with streptococcal infection:
      Sydenham chorea, PANDAS, and PANDAS variants.
AB  - Streptococcal infection in children is usually benign and self-limited. In a
      small percentage of children, prominent neurologic and/or psychiatric sequelae
      can occur. Sydenham chorea is the best defined and best recognized. PANDAS
      (pediatric autoimmune neuropsychiatric disorders associated with streptococcal
      infection) is a well-defined syndrome in which tics (motor and/or vocal) and/or
      obsessive-compulsive disorder consistently exacerbate in temporal correlation to
      a group A beta-hemolytic streptococcal infection. PANDAS constitutes a subset of
      children with tics, Tourette syndrome, and obsessive-compulsive disorder. In
      addition to strictly defined PANDAS, we and others have recognized several PANDAS
      variants, including adult-onset variant, a dystonic variant, a myoclonic variant,
      and a "chronic" PANDAS variant. The nosology and classification of these entities
      are rapidly evolving. The recognition that some pediatric neurobehavioral
      syndromes have infectious and/or immunologic triggers points to important new
      avenues of disease treatment. In this review, we summarize this complex and
      rapidly evolving area of clinical research.

PMID- 16970876
TI  - Neurologic and radiologic manifestations of three girls surviving acute carbon
      monoxide poisoning.
AB  - We report the neurologic and radiologic manifestations of three adolescent girls
      with acute carbon monoxide poisoning. The girls were found collapsed and
      unconscious in a bathroom where liquid petroleum gas was being used as heating
      fuel. As hyperbaric oxygen therapy was not available locally, they only received
      oxygen supplementation via nasal cannula (4 L/minute) as treatment in the first 2
      days. On transfer to a tertiary center in Hong Kong, evolving neurologic
      manifestations of visual acuity and field deficits, confusion, and focal motor
      weaknesses were observed. Focal infarctions were evident in cerebral computed
      tomography in one patient and cortical lesions on magnetic resonance imaging in
      all three patients. [18F]Fluorodeoxyglucose (FDG) positron emission tomography
      (PET) revealed additional decreased metabolism in the basal ganglia in two
      patients, which was typical of carbon monoxide poisoning. The neurologic deficits
      resolved completely at 3 weeks after the exposure, but psychologic symptoms
      succeeded. This report serves to alert clinicians to the varied neuro
      ophthalmologic manifestations and psychologic impairment even with the same
      duration of carbon monoxide poisoning. PET might be more sensitive in detecting
      cerebral injuries specific for carbon monoxide poisoning.

PMID- 16970877
TI  - Confirmation of tuberous sclerosis complex by high-resolution ultrasonography.

PMID- 16970878
TI  - Magnetic resonance imaging (MRI) findings in children surviving extremely
      premature delivery and extremely low birthweight with cerebral palsy.
AB  - To delineate the frequency, severity, and characteristics of the brain injury
      occurring in children surviving extremely premature birth, we reviewed brain
      magnetic resonance images (MRIs) of children with cerebral palsy whose
      birthweight was less than 1000 g and whose gestational age was less than 28
      weeks. The patients were all enrolled in the state Children's Rehabilitative
      Services clinic, where cerebral palsy is an automatic qualifying condition. We
      tabulated the MRI findings with respect to the cerebellum, periventricular white
      matter, and corpus callosum. The inclusion criteria were met by 157 children; 94
      had an MRI. The available scans were reviewed by the authors, and the findings
      were tabulated. Fifty scans were available for review. There were 4 totally
      normal scans, 18 scans had normal cerebellar imaging, and 8 scans were felt to
      have normal cerebral findings. The common cerebral abnormalities included
      decreased white-matter volume without gliosis (n = 36), periventricular
      leukomalacia (n = 16), and a thin corpus callosum (n = 18). Cerebellar
      abnormalities were found in 32. The cerebellar findings included destruction of
      major portions of the cerebellum (usually the inferior vermis and hemispheres) (n
      = 23) and focal or unilateral loss of cerebellar tissue (n = 4). The high
      incidence of injury to the cerebellum has not been previously appreciated. The
      most common cerebral injury is decreased volume of white matter in the
      periventricular regions without gliosis. The pattern of cerebellar injury
      suggests a vascular insult, and the deficient white matter without gliosis
      suggests immaturity of oligodendrogliocytes with limited response to injury. Both
      lesions are more or less unique to the age at which the insult occurred and
      represent an emerging, newly recognized type of cerebral palsy.

PMID- 16970879
TI  - Increased antistreptococcal antibody titers and anti-basal ganglia antibodies in
      patients with Tourette syndrome: controlled cross-sectional study.
AB  - The association between Tourette syndrome, attention-deficit hyperactivity
      disorder (ADHD), and obsessive-compulsive disorder following streptococcal
      infections has been documented, but with conflicting reports. We thus felt it was
      important to investigate this association in a group of Italian patients not
      previously documented. We took blood on 69 patients with Tourette syndrome and 72
      age- and sex-matched tic-free controls. Laboratory staff were blind to the
      diagnostic status of the subjects. Evidence of recent streptococcal infection was
      defined using antistreptolysin titers. Anti-basal ganglia antibodies were
      determined using human basal ganglia sections. Statistical analysis was conducted
      using analysis of variance and chi-square tests. Raised antistreptolysin titers
      were found in 41 of 69 (59%) patients with Tourette syndrome and 14 of 72 (19%)
      controls (P = .000). Positive anti-basal ganglia antibodies were found in 22 of
      69 (32%) subjects with Tourette syndrome compared with 7 of 72 (10%) controls,
      which was also significant (P = .002). Raised antistreptolysin titers were
      detected in 18 of 22 (82%) patients with Tourette syndrome with positive anti
      basal ganglia antibodies and 22 of 47 (47%) patients with negative anti-basal
      ganglia antibodies (P = .01). These results support the reported association
      between streptococcal infection and anti-basal ganglia antibodies and some
      patients with Tourette syndrome.

PMID- 16970880
TI  - Association of adenosine deaminase polymorphism with mild mental retardation.
AB  - The etiology of mild mental retardation remains undefined in about 60% of cases.
      Even though the causes of mild mental retardation are likely to be heterogeneous,
      the evidence for genetic involvement is increasing, along with the development of
      specific diagnostic techniques. To improve our understanding of the genetic basis
      of mild mental retardation, we explored the role of polymorphisms of adenosine
      deaminase, an enzyme that is supposed to act as a neuroregulatory protein. To
      this end, we conducted an association study comparing children with mild mental
      retardation of unknown origin with two groups of controls: (1) apparently healthy
      children and (2) children with moderate or severe mental retardation of known
      etiology. Overall, 338 participants were enrolled in the study. Cases (ie, 80
      children) were more likely than controls (ie, 153 healthy children and 105
      children with moderate or severe mental retardation) to have the low-activity ADA
      Asn 8 (ADA(1) *2) polymorphism (P < .05) and to present the ADA(1) *2/ ADA(2) *1
      haplotype. No significant differences were found with respect to adenosine
      deaminase polymorphisms when comparing the group with moderate or severe mental
      retardation of known causes and healthy controls. In conclusion, our findings
      suggest a possible role for a low-activity genotype (ADA-8Asn) (ADA(1) *2) of
      adenosine deaminase in the pathogenesis of mild mental retardation.

PMID- 16970881
TI  - Epileptic features of patients with unilateral and bilateral schizencephaly.
AB  - The extent of cortical maldevelopment might correlate with the severity of the
      clinical manifestation, such as cognitive delay or motor dysfunction. The
      objective of this study was to investigate the clinical features of epilepsy in
      patients with unilateral and bilateral schizencephaly. We studied 44 consecutive
      patients with schizencephaly diagnosed by magnetic resonance imaging (MRI). The
      epileptic features were analyzed in detail: frequency of epilepsy, median age at
      onset of epilepsy, semiology of seizures, characteristic features of
      electroencephalographic (EEG) abnormalities, epileptic syndromes, and
      antiepileptic drug treatment. We also verified the presence of motor
      disabilities. Data were analyzed according to the presence of unilateral or
      bilateral clefts and to the presence of open-lip versus closed-lip
      schizencephaly. We used the chi-square test and Fisher exact test for statistical
      analysis. Twenty-four patients had a unilateral cleft (group 1) and 20 patients
      had bilateral clefts (group 2). Ages ranged from 1 to 37 years (mean 10.6 years).
      Epilepsy was present in 15 (63%) patients in group 1 and in 11 (55%) patients of
      group 2; a history of status epilepticus occurred in 13% of group 1 and in 27% in
      group 2; and a history of clusters of seizures occurred in 40% of group 1 and in
      45% of group 2. Eight (53%) patients in group 1 and 6 (54%) patients in group 2
      were in monotherapy. Ten (67%) patients in group 1 and 7 (64%) patients in group
      2 had seizures controlled with antiepileptic drugs. The frequency of EEG
      abnormalities was similar between groups (75% and 85%, groups 1 and 2,
      respectively). Statistical analysis showed no difference between the two groups
      in the variables mentioned above. However, motor disability was significantly
      more frequent and more severe in group 2. Regarding the type of schizencephaly
      (open lip versus closed lip), there was no difference in the frequency of
      patients with epilepsy, and severe motor deficit was more frequently found in
      bilateral and open-lip schizencephaly. The extent of the cortical maldevelopment
      in patients with schizencephaly does not correlate with the severity of the
      clinical and EEG features of epilepsy, unlike the cognitive and motor
      manifestations. In addition, the type of schizencephaly (open lip versus closed
      lip) does not correlate with the presence of epilepsy or seizure control, unlike
      motor deficit.

PMID- 16970882
TI  - Sleep disturbance in children with migraine.
AB  - The objectives of this study were to determine if (1) children with migraine
      experience greater sleep disturbances than their siblings, (2) those with more
      severe migraine have greater levels of sleep disruption, and (3) these sleep
      disturbances lead to greater behavioral problems and more missed school. Children
      aged 6 to 18 years with a diagnosis of migraine for > 6 months, who had at least
      one sibling without migraine in the same age range, were identified through our
      neurology clinic database or at the time of the clinic visit. Parents completed
      the (1) demographic, general health, and migraine information questionnaire; (2)
      Child Sleep Habits Questionnaire; and (3) Behavior Assessment System for
      Children: Second Edition (BASC-2) Parent Rating Scales for each child. Cases with
      migraine had higher total sleep (P < .02), sleep delay (P < .03), and daytime
      sleepiness scores (P < .001) than controls. Cases with more severe migraines had
      higher total sleep (P < .01) and sleep duration scores (P < .03) than those with
      milder headaches. In cases, higher total sleep scores predicted greater behavior
      problems on all four composite scales on the Behavior Assessment System for
      Children: Second Edition (Externalizing Problems, P < .05; Internalizing
      Problems, P < .005; Behavior Systems Index, P < .003; and Adaptability Skills, P
      < .006). We conclude that children with migraine are prone to greater sleep and
      behavioral disturbances than children without headache. Sleep disorders should be
      routinely queried and appropriate advice on sleep hygiene provided.

PMID- 16970883
TI  - Outcome of children with juvenile absence epilepsy.
AB  - The incidence and natural history of childhood absence epilepsy are well
      documented, but those of juvenile absence epilepsy are poorly delineated. We
      conducted a retrospective chart study to evaluate the incidence and outcome of
      patients with juvenile absence epilepsy by retrieving the medical records of
      consecutive patients with juvenile absence epilepsy who were evaluated in three
      pediatric neurology outpatient clinics in Israel. Inclusion criteria included the
      onset of epilepsy after the age of 10 years and follow-up until at least 15 years
      of age. The patients with an electroencephalogram (EEG) suggestive of myoclonic
      epilepsy (polyspike and wave) were excluded from the study. Seventeen patients
      (10 female and 7 male) fulfilled the inclusion criteria for juvenile absence
      epilepsy. They presented with epilepsy at a mean age of 11.94 years (range 10
      16.5 years). The mean duration of follow-up was 6.05 years (range 2-12 years).
      Five patients (29.4%) had a family history of epilepsy. All 17 patients had a
      normal neurodevelopmental status. Eight patients (47%) experienced generalized
      tonic-clonic seizures. At follow-up, eight patients (43.7%) were seizure free.
      Only three (37.5%) of the patients who experienced generalized tonic-clonic
      seizures were seizure free during follow-up compared with five (55.5%) patients
      without generalized tonic-clonic seizures. Our results indicate that the outcome
      of patients with juvenile absence epilepsy is less favorable than children with
      childhood absence epilepsy and that the presence of generalized tonic-clonic
      seizures is a predictor for poorer outcome.

PMID- 16970884
TI  - Vulnerability of the anterior commissure in moderate to severe pediatric
      traumatic brain injury.
AB  - In relation to the adult brain, the immature brain might be more vulnerable to
      damage during and following traumatic brain injury, particularly in white-matter
      tracts. Given well-established evidence of corpus callosum atrophy, we
      hypothesized that anterior commissure volume (using quantitative magnetic
      resonance imaging [MRI]) in this structure would be decreased in children with
      moderate to severe traumatic brain injury relative to typically developing
      children. Second, given the purported role of the anterior commissure in
      interhemispheric axon conveyance between temporal lobes, we hypothesized that
      temporal lobe white matter, temporal lesion volume, and injury severity (Glasgow
      Coma Scale score) would be predictive of decreased anterior commissure cross
      sectional volume in patients with traumatic brain injury. Finally, we wished to
      establish the relationship between the anterior commissure and the temporal stem,
      a major white-matter tract into the temporal lobes, using diffusion tensor
      imaging fiber-tracking maps for each patient. We also hypothesized that children
      with traumatic brain injury would exhibit decreased fractional anisotropy in
      relation to typically developing children in a fiber system including the
      anterior commissure and the temporal lobes. Decreased anterior commissure cross
      sectional volume was observed in patients with traumatic brain injury, and, as
      predicted, anterior commissure and temporal white-matter volumes were positively
      related to each other and to higher Glasgow Coma Scale scores. Lesion volume was
      not independently predictive of anterior commissure volume in the overall model.
      Diffusion tensor imaging fractional anisotropy values differed between the groups
      for the temporal stem-anterior commissure system, with the traumatic brain injury
      group exhibiting decreased fractional anisotropy. The anterior commissure, like
      the corpus callosum, appears to be highly vulnerable to white-matter degenerative
      changes resulting from mechanisms such as the direct impact of trauma,
      progressive axonal injury as tissue in other brain regions atrophies, or myelin
      degeneration. This is the first systematic examination of anterior commissure
      atrophy following traumatic brain injury using in vivo quantitative MRI and
      diffusion tensor imaging fiber tracking in pediatric subjects.

PMID- 16970886
TI  - Pediatric experience with sudden unexplained death in epilepsy at a tertiary
      epilepsy center.
AB  - Sudden unexplained death in epilepsy is rare in children, and few studies report
      risk factors. We reviewed our experience with 17 cases of sudden unexplained
      death in epilepsy to determine risk factors in children. The charts of all
      patients with onset of epilepsy at less than age 18 years who suffered sudden
      unexplained death in epilepsy between August 1992 and April 2004 at our epilepsy
      center were retrospectively reviewed. Deaths were classified as possible,
      probable, or definite sudden unexplained death in epilepsy. There were seven
      cases of definite, nine cases of probable, and one case of possible sudden
      unexplained death in epilepsy. Generalized tonic-clonic seizures and prone
      position during sleep were found to be major risk factors. Sudden unexplained
      death in epilepsy in children and adolescents is associated with convulsive
      seizures, and aggressive treatment of nocturnal generalized tonic-clonic seizures
      might help lower the occurrence.

PMID- 16970885
TI  - Mental retardation and epilepsy in patients with isolated cerebellar hypoplasia.
AB  - Congenital nonprogressive cerebellar ataxia includes a complex group of disorders
      with heterogeneous phenotypic and etiopathogenetic characteristics. Despite
      recent advances in the understanding of the role of the cerebellum in cognition
      and behavior, the opinion that the clinical presentation of congenital cerebellar
      diseases is principally linked to motor dysfunction is common. This is largely
      due to the lack of well-organized epidemiologic studies on the prevalence of
      nonmotor disturbances in cerebellar disease. The association between congenital
      cerebellar disease and epilepsy has rarely been described. We report clinical,
      neurophysiologic, neuroimaging, and neuropsychologic features in a group of 14
      patients with congenital nonprogressive cerebellar ataxia associated with
      cerebellar hypoplasia, 5 of whom have familial disease, aiming to further a
      better knowledge of the prevalence of cognitive and/or emotional impairment and
      epilepsy. The results confirm that cerebellar hypoplasia predisposes individuals
      to psychomotor delay (71.4%) and cognitive impairment (85.7%). Moreover, the
      tendency toward abnormal electroencephalographic (EEG) findings (78.5%),
      associated in a minor percentage of cases with epilepsy (28.5%), is also evident
      in our study.

PMID- 16970887
TI  - Specific neurologic complications of human immunodeficiency virus type 1 (HIV-1)
      infection in children.
AB  - Pediatric human immunodeficiency virus type 1 (HIV-1) infection is endemic
      throughout southern Africa. Neurologic complications are described in 20% to 60%
      of published series, mostly related to HIV-1 encephalopathy. With increasing HIV
      prevalence, more atypical cases are presenting. We present, as illustrative
      cases, seven children (three girls) with unusual neurologic sequelae as a
      consequence of HIV-1 infection. The median age at presentation was 33 months
      (range 7 months-6 years). Five of the seven children were developmentally normal
      before presentation. They presented with progressive multifocal
      leukoencephalopathy, myelopathy, intractable seizures, acute vasculitis and
      blindness, hemiplegia, peripheral neuropathy, and paraspinal lymphoma.
      Neuroimaging of the brain was performed in five patients, of whom one had basal
      ganglia calcification. All children had poor outcome with incomplete recovery or
      continued deterioration. In conclusion, children with HIV-1 infection who survive
      beyond the first year of life can present with a wide variety of neurologic
      complications. A similar spectrum of neurologic manifestations is likely to occur
      in other sub-Saharan African countries, characterized by high HIV prevalence. The
      case histories demonstrate that the neurologic features of pediatric HIV
      infection do not easily fit into a simplified classification system.

PMID- 16970888
TI  - Maternal risk factors for term neonatal seizures: population-based study in
      Colorado, 1989-2003.
AB  - Neonatal seizures in term infants are rare but have important potential
      implications for brain development. Risk factors for neonatal seizures in term
      infants have been less well defined than those among preterm infants. To evaluate
      the relationship between maternal risk factors and neonatal seizures in the first
      72 hours of life in term infants, a case-control study using the Colorado Birth
      Certificate Registry was conducted. Term neonates in all hospitals in Colorado
      with and without seizures in the first 72 hours were studied. After adjusting for
      vaginal delivery in the setting of herpes infection and post-term delivery,
      preexisting diabetes in the mother (odds ratio 4.30, 95% confidence interval 1.64
      11.27, P < .01) and fetal distress (odds ratio 5.88, 95% confidence interval 4.60
      7.13, P < .0001) were independent risk factors for neonatal seizures in term
      infants. These findings are confirmatory of previous reports that maternal
      preexisting diabetes and fetal distress increase the risk of neonatal seizure in
      term infants. Although we cannot establish the pathophysiology of neonatal
      seizures from this analysis, hypoxic-ischemic brain injury and hypoglycemia in
      infants of diabetic mothers are known causes of neonatal seizures that can be
      represented in this analysis by fetal distress and maternal preexisting diabetes,
      respectively. Maternal diabetic vasculopathy can also be a contributing factor.

PMID- 16970889
TI  - Bispectral index monitoring in confirmation of brain death in children.
AB  - Although the guidelines for the diagnosis of brain death in children are well
      established, the diagnosis is still under debate, and further confirmatory tests
      are required. Performing these confirmatory tests presents some drawbacks, such
      as high costs, the need for specialized personnel and technology, transportation
      of patients out of the intensive care unit, and the use of contrast media.
      Bispectral index monitoring can provide real-time, objective, continuous
      monitoring of the consciousness level in critically ill children. The aim of this
      prospective study was to define the role of bispectral index monitoring in the
      confirmation and diagnosis of brain death. Eight children who had fulfilled the
      diagnostic criteria of brain death were included in the study. The age of
      patients ranged from 3 months to 15 years. All patients had electrocerebral
      silence on their electroencephalographic recordings. After the diagnosis of brain
      death, at least 2-hour monitoring was performed, and all patients expressed a
      score of 0, indicating brain death. According to our study, the decrease in
      bispectral index score to 0 in patients with suspected brain death can support
      and confirm brain death diagnosis in children and can enable scheduling of
      expensive tests, such as cerebral angiography, in the appropriate time.
      Nevertheless, further studies are needed to determine the role of the bispectral
      index in the diagnosis and confirmation of brain death in children. In this
      article, we review clinical utility, application time, and interpretation of
      bispectral index monitoring in confirmation of brain death diagnosis in children.

PMID- 16970890
TI  - Proton magnetic resonance spectroscopy and diffusion-weighted imaging in isolated
      sulfite oxidase deficiency.
AB  - Isolated sulfite oxidase deficiency is a rare autosomal recessive disorder of the
      newborn that can be mistaken for neonatal asphyxia. Diffusion-weighted imaging of
      the brain demonstrates widespread diffusion restriction, and proton magnetic
      resonance spectroscopy shows an elevated lactate level, a decrease in the ratio
      of N-acetylaspartate to creatine, and a rise in the ratio of choline to creatine.
      This precedes severe cystic encephalomalacia and suggests that the energy failure
      associated with neuronal dysfunction and myelin disintegration occurs early in
      isolated sulfite oxidase deficiency.

PMID- 16970891
TI  - Stroke associated with Barth syndrome.
AB  - Barth syndrome is an inherited disorder characterized by dilated cardiomyopathy,
      neutropenia, growth retardation, and skeletal myopathy. We describe a case of
      acute stroke owing to Barth syndrome that required intra-arterial thrombolysis.
      This case suggests that cardiovascular complications can be observed in patients
      with Barth syndrome. Stroke prevention measures, including the use of
      antithrombotic agents, might be warranted.

PMID- 16970892
TI  - Recurrent absence status epilepticus (spike-and-wave stupor) associated with
      lamotrigine therapy.
AB  - We report on the aggravation of absence seizures by lamotrigine leading to
      absence status epilepticus in a child. The patient is a 10-year-old girl with a
      history of absence seizures, learning disabilities, and hereditary neuropathy
      with liability to pressure palsies. Lamotrigine (up to 12 mg/kg/day) was
      prescribed after a brief course of valproate was associated with restlessness.
      Long-acting methylphenidate was also administered. The initial response to
      lamotrigine appeared to be excellent. The first episode of absence status
      epilepticus occurred during a febrile illness while lamotrigine was being
      gradually discontinued. Following this event, lamotrigine dose was increased to
      10 mg/kg/day and methylphenidate was continued. Six weeks later, a second absence
      status epilepticus episode ensued without fever. Sulthiame and clonazepam were
      substituted for lamotrigine, whereas methylphenidate therapy was continued. A
      psychiatrist prescribed risperidone 1 month later owing to obsessive-compulsive
      behavior. Nine months later, she remained free of absence seizures. Whereas the
      first absence status epilepticus event could have been triggered by fever, the
      second episode occurred while the daily lamotrigine dose was being increased.
      Moreover, the patient is seizure free following lamotrigine discontinuation.
      Hence, it is quite possible that lamotrigine caused seizure aggravation and
      absence status epilepticus in this child.

PMID- 16970894
TI  - Focal cerebral pathology presenting as tonic seizures.
AB  - We report a case of a 14-year-old boy with a dysembryoplastic neuroepithelial
      tumor and mental retardation with intractable seizures, which were demonstrated
      to be predominantly tonic seizures by video-electroencephalography (EEG). He did
      not have any electrographic evidence of Lennox-Gastaut syndrome. Head magnetic
      resonance imaging (MRI) revealed a right parietal dysembryoplastic
      neuroepithelial tumor. He has been seizure free since surgical removal of the
      tumor. Clinicians need to be aware that tonic seizures can be associated with an
      underlying focal pathology that might be treatable.

PMID- 16970893
TI  - Predictors of scoliosis in Rett syndrome.
AB  - Scoliosis is a common clinical manifestation of Rett syndrome, a
      neurodevelopmental disorder that almost exclusively affects girls. Following
      apparently normal development, these girls typically regress and lose previously
      attained cognitive, social, and motor skills. Severe intellectual and physical
      disabilities remain throughout life. Mutations in the methyl-CpG-binding protein
      2 gene, MECP2, are detected in approximately 80% of cases and are associated with
      phenotypic variability. Population-based data on Australian cases were used to
      study the association between early developmental and genetic factors and the
      onset of scoliosis. The median age at scoliosis onset was 9.80 years, and three
      quarters of subjects had developed scoliosis by 13 years of age. Children with
      compromised early development before 6 months, those who were less mobile at 10
      months, and those who never walked were more likely to have an earlier onset of
      scoliosis. When seven common point mutations and large genomic and C-terminal
      deletions were compared, the R294X mutation appeared to provide some protective
      effect against the development of scoliosis.

PMID- 16970895
TI  - Epilepsy and neuropsychologic deficit in a child with cerebellar astrocytoma.
AB  - We report the case of a 32-month-old female patient presenting with cerebellar
      pilocytic astrocytoma with epileptic seizures, psychomotor delay, and severe
      language delay. Usually, the typical onset of cerebellar tumor is characterized
      by raised intracranial pressure and cerebellar incoordination. A review of the
      few cases reported in the literature evidencing epileptic seizures symptomatic of
      a focal, nondegenerative mass limited to the cerebellum is included. Moreover, a
      discussion about the cerebellar contribution to nonmotor functions in children is
      presented, in particular following tumor resection.

PMID- 16970896
TI  - Refractory status epilepticus owing to human parvovirus B19 encephalitis in a
      child.
AB  - Human parvovirus B19 is the agent that causes erythema infectiosum (fifth
      disease), a disease that is generally benign and self-limiting. This virus also
      is associated with severe disease in hemolytic or immunocompromised patients. It
      rarely causes meningoencephalitis in healthy children. Herein we present the case
      of a 10-year-old healthy girl with refractory status epilepticus possibly owing
      to human parvovirus B19 encephalitis who was successfully treated with high-dose
      corticosteroids. To our knowledge, this is the first report of human parvovirus
      B19 encephalitis complicated by refractory status epilepticus in a child.

PMID- 16970897
TI  - Is atomoxetine also effective in patients suffering from Tourette syndrome?

PMID- 16970898
TI  - Quality assessment of commercial small interfering RNA and DNA: monoclonal
      antibodies and a high-throughput chemiluminescence assay.

PMID- 16970899
TI  - Differential enrichment of high- and low-molecular weight proteins and concurrent
      RNA extraction.

PMID- 16970900
TI  - Using a modified TA cloning method to create entry clones.
AB  - We describe a noncommercial alternative method to create entry clones compatible
      with all kinds of destination vectors based on an improved TA cloning approach.
      To generate Gateway T vectors, we first constructed gentamicin- and
      chloramphenicol-resistant entry vectors designated pGWG and pGWC, respectively.
      Each entry vector contains an AhdI cassette flanked by attL sites, with each AhdI
      cassette containing two AhdI restriction enzyme sites spaced by the ccdB killer
      gene, which is lethal to most Escherichia coli strains. Gateway T vectors can be
      prepared by simple digestion of these entry vectors with the AhdI enzyme or its
      isoschizomers. The use of the ccdB gene as a negative selection marker is an
      important improvement over conventional TA cloning in that it eliminates the
      necessity of blue/white color screening based on alpha-complementation. Another
      important improvement that we have implemented is to retail the T vectors using
      Taq polymerase and dTTP so as to improve the cloning efficiency. Together, these
      improvements allow TA cloning to realize its full potential. Using Gateway T
      vectors prepared by this improved method, entry clones for PCR products or
      restriction enzyme fragments can be created simply, efficiently, and
      inexpensively while at the same time introducing greater compatibility.

PMID- 16970901
TI  - A high-yield one-step purification method using copper-chelating chromatography
      for recombinant proteins fused with maltose-binding protein.

PMID- 16970902
TI  - Enrichment of circularized target DNA by inverse polymerase chain reaction.

PMID- 16970903
TI  - Protein-DNA interaction-based detection of small molecules by employing Renilla
      luciferase fusion protein: quantitative and generic measurement of tetracyclines
      with a Renilla luciferase-tagged Tet repressor protein.

PMID- 16970904
TI  - The diverse sesquiterpene profile of patchouli, Pogostemon cablin, is correlated
      with a limited number of sesquiterpene synthases.
AB  - Pogostemon cablin (patchouli), like many plants within the Lamiaceae, accumulates
      large amounts of essential oil. Patchouli oil is unique because it consists of
      over 24 different sesquiterpenes, rather than a blend of different mono-, sesqui-
      and di-terpene compounds. To determine if this complex mixture of sesquiterpenes
      arises from an equal number of unique sesquiterpene synthases, we developed a RT
      PCR strategy to isolate and functionally characterize the respective patchouli
      oil synthase genes. Unexpectedly, only five terpene synthase cDNA genes were
      isolated. Four of the cDNAs encode for synthases catalyzing the biosynthesis of
      one major sesquiterpene, including a gamma-curcumene synthase, two germacrene D
      synthases, and a germacrene A synthase. The fifth cDNA encodes for a patchoulol
      synthase, which catalyzes the conversion of FPP to patchoulol plus at least 13
      additional sesquiterpene products. Equally intriguing, the yield of the different
      in vitro reaction products resembles quantitatively and qualitatively the profile
      of sesquiterpenes found in patchouli oil extracted from plants, suggesting that a
      single terpene synthase is responsible for the bulk and diversity of terpene
      products produced in planta.

PMID- 16970905
TI  - Phosphorylation of myorod (catchin) by kinases tightly associated to molluscan
      and vertebrate smooth muscle myosins.
AB  - Myorod, also known as catchin, a newly discovered component of molluscan smooth
      muscle thick filaments, is an alternative product of the myosin heavy chain gene.
      It contains a C-terminal rod part that is identical to that part of myosin and a
      unique N-terminal domain that is very small relative to the myosin head domain.
      The role of myorod in contraction or relaxation of this muscle type is unknown.
      In the present study we demonstrated that myorod was phosphorylated not only by a
      kinase endogenous to molluscan myosin and twitchin but also to vertebrate smooth
      muscle myosin light chain kinase (MLCK). The rates and maximal levels of
      phosphorylation were up to threefold higher than those observed by protein kinase
      A with clear optima at the physiological salt concentrations. Using a mild
      digestion with chymotrypsin we isolated an 11 kDa phosphopeptide and showed that
      the phosphorylation site was located at the N-terminal domain of myorod at Thr
      141 position. The sequence around this site exhibited a high degree of similarity
      to that expected for the substrate recognition site of MLCK. The phosphorylation
      rates strongly depended on the ionic conditions indicating that this site could
      be readily sterically blocked during myorod polymerization. Another component of
      the thick filaments involved in regulation of the catch state, twitchin, was
      phosphorylated by MLCK and exhibited endogenous myorod kinase and MLCK
      activities. A possible role of these phosphorylation reactions in the regulation
      of molluscan smooth muscles is discussed.

PMID- 16970906
TI  - Fluoroalcohols induced unfolding of Succinylated Con A: native like beta
      structure in partially folded intermediate and alpha-helix in molten globule like
      state.
AB  - Concanavalin A (Con A) exists in dimeric state at pH 5. In concentration range 20
      60% (v/v) 2,2,2-trifluoroethanol (TFE) and 2-40% (v/v) 1,1,1,3,3,3
      hexafluoroisopropanol (HFIP), Con A at pH 5.0 shows visible aggregation. However,
      when succinyl Con A was used, no aggregation was observed in the entire
      concentration range of fluoroalcohols (0-90% v/v TFE and HFIP) and resulted in
      stable alpha-helix formation. Temperature-induced concentration-dependent
      aggregation in Con A was also found to be prevented/reduced in succinylated form.
      Possible role of electrostatic repulsion among residues in the prevention of
      hydrophobically driven aggregation has been discussed. Results indicate that
      succinylation of a protein resulted in greater stability (in both beta-sheet and
      alpha-helical forms) against alcohol-induced and temperature-induced
      concentration-dependent aggregation and this observation may play significant
      role in amyloid-forming proteins. Effect of TFE and HFIP on the conformation of a
      dimeric protein, Succinylated Con A, has been investigated by circular dichroism
      (CD), fluorescence emission spectroscopy, binding of hydrophobic dye ANS (8
      anilinonaphthalene-1-sulfonic acid). Far UV-CD, a probe for secondary structure
      shows loss of native secondary structure in the presence of low concentration of
      both the alcohols, TFE (10% v/v) and HFIP (4% v/v). Upon addition of higher
      concentration of these alcohols, Succinylated Con A exhibited transformation from
      beta-sheet to alpha-helical structure. Intrinsic tryptophan fluorescence studies,
      ANS binding and near UV-CD experiments indicate the protein is more expanded,
      have more exposed hydrophobic surfaces and highly disrupted tertiary structure at
      60% (v/v) TFE and 30% (v/v) HFIP concentrations. Taken together, these results it
      might be concluded that TFE and HFIP induce two intermediate states at their low
      and high concentrations in Succinyl Con A.

PMID- 16970907
TI  - Gating of the ATP-sensitive K+ channel by a pore-lining phenylalanine residue.
AB  - ATP-sensitive K(+) (K(ATP)) channels are gated by intracellular ATP, proton and
      phospholipids. The pore-forming Kir6.2 subunit has all essential machineries for
      channel gating by these ligands. It is known that channel gating involves the
      inner helix bundle of crossing in which a phenylalanine residue (Phe168) is found
      in the TM2 at the narrowest region of the ion-conduction pathway in the Kir6.2.
      Here we present evidence that Phe168-Kir6.2 functions as an ATP- and proton
      activated gate via steric hindrance and hydrophobic interactions. Site-specific
      mutations of Phe168 to a small amino acid resulted in losses of the ATP- and
      proton-dependent gating, whereas the channel gating was well maintained after
      mutation to a bulky tryptophan, supporting the steric hindrance effect. The
      steric hindrance effect, though necessary, was insufficient for the gating, as
      mutating Phe168 to a bulky hydrophilic residue severely compromised the channel
      gating. Single-channel kinetics of the F168W mutant resembled the wild-type
      channel. Small residues increased P(open), and displayed long-lasting closures
      and long-lasting openings. Kinetic modeling showed that these resulted from
      stabilization of the channel to open and long-lived closed states, suggesting
      that a bulky and hydrophobic residue may lower the energy barrier for the switch
      between channel openings and closures. Thus, it is likely that the Phe168 acts as
      not only a steric hindrance gate but also potentially a facilitator of gating
      transitions in the Kir6.2 channel.

PMID- 16970908
TI  - PKCdelta-mediated IRS-1 Ser24 phosphorylation negatively regulates IRS-1
      function.
AB  - The IRS-1 PH and PTB domains are essential for insulin-stimulated IRS-1 Tyr
      phosphorylation and insulin signaling, while Ser/Thr phosphorylation of IRS-1
      disrupts these signaling events. To investigate consensus PKC phosphorylation
      sites in the PH-PTB domains of human IRS-1, we changed Ser24, Ser58, and Thr191
      to Ala (3A) or Glu (3E), to block or mimic phosphorylation, respectively. The 3A
      mutant abrogated the inhibitory effect of PKCdelta on insulin-stimulated IRS-1
      Tyr phosphorylation, while reductions in insulin-stimulated IRS-1 Tyr
      phosphorylation, cellular proliferation, and Akt activation were observed with
      the 3E mutant. When single Glu mutants were tested, the Ser24 to Glu mutant had
      the greatest inhibitory effect on insulin-stimulated IRS-1 Tyr phosphorylation.
      PKCdelta-mediated IRS-1 Ser24 phosphorylation was confirmed in cells with
      PKCdelta catalytic domain mutants and by an RNAi method. Mechanistic studies
      revealed that IRS-1 with Ala and Glu point mutations at Ser24 impaired
      phosphatidylinositol-4,5-bisphosphate binding. In summary, our data are
      consistent with the hypothesis that Ser24 is a negative regulatory
      phosphorylation site in IRS-1.

PMID- 16970909
TI  - TTF-1, a homeodomain-containing transcription factor, regulates feeding behavior
      in the rat hypothalamus.
AB  - TTF-1 is a member of the NKx family of homeodomain genes, and is required for
      morphogenesis and fetal diencephalon development. Our previous studies have shown
      that TTF-1 expression is maintained in some regions of the postnatal rat brain
      and transactivates the gene expression of several neuropeptides. In this study, a
      potential role for TTF-1 in the regulation of feeding behavior was identified.
      Immunohistochemical analysis showed that TTF-1 is present in several hypothalamic
      nuclei of the adult rat brain involved in the control of feeding behavior. Food
      deprivation for two days markedly increased the hypothalamic levels of TTF-1 mRNA
      and protein. Intracerebroventricular administration of an antisense TTF-1
      oligodeoxynucleotide significantly decreased TTF-1 protein abundance in the
      hypothalamus. This TTF-1 decrease was followed by a significant decrease in
      neuropeptide Y mRNA content and an increase in proopiomelanocortin mRNA content,
      and in turn resulted in a decrease of the animal's food intake and body weight.
      These results suggest a novel role for TTF-1 in the regulation of feeding
      behavior in the rat hypothalamus.

PMID- 16970910
TI  - Human serum albumin supported lipid patterns for the targeted recognition of
      microspheres coated by membrane based on ss-DNA hybridization.
AB  - Human serum albumin (HSA) patterns have been successfully fabricated for the
      deposition of lipid bilayer, 1,2-dimyristoyl-sglycerophosphate (DMPA), by making
      use of the micro-contact printing (microCP) technique and liposome fusion.
      Confocal laser scanning microscopy (CLSM) results indicate that lipid bilayer has
      been assembled in HSA patterns with a good stability. Such well-defined lipid
      patterns formed on HSA surface create possibility to incorporate specific
      components like channels or receptors for specific recognition. In view of this,
      microspheres coated with lipid membranes were immobilized in HSA-supported lipid
      patterns via the hybridization of complementary ss-DNAs. This procedure enables
      to transfer solid materials to a soft surface through a specific recognition.

PMID- 16970911
TI  - NMR solution structure of BmK-betaIT, an excitatory scorpion beta-toxin without a
      'hot spot' at the relevant position.
AB  - BmK-betaIT (previously named as Bm32-VI in the literature), an excitatory
      scorpion beta-toxin, is purified from the venom of the Chinese scorpion Buthus
      martensii Karsch. It features a primary sequence typical of the excitatory anti
      insect toxins: two contiguous Cys residues (Cys37-Cys38) and a shifted location
      of the fourth disulfide bridges (Cys38-Cys64), and demonstrates bioactivity
      characteristic of the excitatory beta-toxins. However, it is noteworthy that BmK
      betaIT is not conserved with a glutamate residue at the preceding position of the
      third Cys residue, and is the first example having a non-glutamate residue at the
      relevant position in the excitatory scorpion beta-toxin subfamily. The 3D
      structure of BmK-betaIT is determined with 2D NMR spectroscopy and molecular
      modeling. The solution structure of BmK-betaIT is closely similar to those of BmK
      IT-AP and Bj-xtrIT, only distinct from the latter by lack of an alpha(0)-helix.
      The surface functional patch comparison with those of BmK IT-AP and Bj-xtrIT
      reveals their striking similarity in the spatial arrangement. These results infer
      that the functional surface of beta-toxins is composed of two binding regions and
      a functional site. The main binding site is consisted of hydrophobic residues
      surrounding the alpha(1)-helix and its preceding loop, which is common to all
      beta-type scorpion toxins affecting Na(+) channels. The second binding site,
      which determines the specificity of the toxin, locates at the C-terminus for
      excitatory insect beta-toxin, while rests at the beta-sheet and its linking loop
      for anti-mammal toxins. The functional site involved in the voltage sensor
      trapping model, which characterizes the function of all beta-toxins, is the
      negatively charged residue Glu15.

PMID- 16970912
TI  - Visfatin in adipocytes is upregulated by hypoxia through HIF1alpha-dependent
      mechanism.
AB  - Obesity is associated with metabolic disorders, such as insulin resistance.
      Visfatin is an adipose-derived secretory factor to exert insulin-mimetic effects.
      Plasma visfatin levels and mRNA levels of visfatin in adipose tissues are
      increased in obesity. However, the mechanism that mediates induction of visfatin
      mRNA in adipose tissue of obesity remains unknown. Recent studies have reported
      that fat tissue is hypoxia in obesity. In this study, we investigated the effects
      of hypoxia on mRNA expression of visfatin in adipocytes. Hypoxia increased
      visfatin mRNA expression. Desferoxamine and Cobaltous chloride, two hypoxia
      mimetic compounds, also increased visfatin mRNA levels. Dimethyloxallyl glycine,
      a stabilizer of hypoxia-inducible factor 1alpha (HIF1alpha), mimicked the hypoxia
      mediated upregulation of visfatin, and YC1, an inhibitor of HIF1 cancelled the
      hypoxia-induced upregulation of visfatin mRNA. We identified two functional
      hypoxia responsive elements (HRE) in mouse visfatin promoter. Hypoxic treatment
      and overexpression of HIF1alpha increased the promoter activity, and mutation of
      the HRE blunted hypoxia-induced activation of visfatin promoter. Our results
      suggest that visfatin mRNA expression is upregulated in the fat tissue of obesity
      through the activation of HIF1alpha pathway due to hypoxia.

PMID- 16970913
TI  - Antioxidant properties of bucillamine: possible mode of action.
AB  - The antioxidant properties of Bucillamine (BUC), a di-thiol compound used for
      treatment of rheumatoid arthritis (RA) and its possible mode of action, were
      investigated. BUC exhibits potent antioxidant activity similar to those of trolox
      and ascorbic acid. It reduces the stable free radical diphenyl-2-picrylhydrazyl
      (DPPH) with IC(50) of 18.5+/-0.1 micromol, its relative antioxidant activity by
      the ferric reducing ability (FRAP) is 2.07+/-0.01 mM and by the trolox equivalent
      antioxidant capacity (TEAC), 1.46+/-0.05 mM. However, its superoxide and apparent
      hydroxyl radical scavenging activities are low (IC(50) at millimolar
      concentrations). We found that BUC is a strong iron (II) and copper (II)
      chelator. This finding is very important since these metal ions are significantly
      higher in RA patients and may be involved in oxidative stress-induced damage. Our
      study suggests that BUC is a potent antioxidant which exerts its beneficial
      therapeutic activities in RA patients by metal chelation rather than by
      scavenging free radical species.

PMID- 16970914
TI  - Enhancement of insulin signaling pathway in adipocytes by oxovanadium(IV)
      complexes.
AB  - Recently, we have found that some oxovanadium(IV) complexes are potent insulin
      mimetic compounds for treating both type I and type II diabetic animals. However,
      the functional mechanism of oxovanadium(IV) complexes is not fully understood. In
      this report, we have shown that oxovanadium(IV)-picolinate complexes such as
      VO(pa)(2), VO(3mpa)(2), and VO(6mpa)(2) act on the insulin signaling pathway in
      3T3-L1 adipocytes. Among them, VO(3mpa)(2) was found to be the highest potent
      activator in inducing not only the phosphotyrosine levels of both IRbeta and IRS
      but also the activation of downstream kinases in the insulin receptor, such as
      Akt and GSK3beta, which in turn translocated the insulin-dependent GLUT4 to the
      plasma membrane. Then, we examined whether or not oxovanadium(IV)-picolinates
      exhibit the hypoglycemic activity in STZ-induced diabetic mice, and found that
      VO(3mpa)(2) is more effective than the others in improving the hyperglycemia of
      the animals. Our present data indicate that both activation of insulin signaling
      pathway, which follows the GLUT4 translocation to the plasma membrane, and
      enhancement of glucose utilization by oxovanadium(IV) complexes cause the
      hypoglycemic effect in diabetic animals.

PMID- 16970915
TI  - Involvement of aberrant DNA methylation on reduced expression of lysophosphatidic
      acid receptor-1 gene in rat tumor cell lines.
AB  - Lysophosphatidic acid (LPA) is a bioactive phospholipid that stimulates cell
      proliferation, migration, and protects cells from apoptosis. It interacts with
      specific G protein-coupled transmembrane receptors. Recently, it has been
      reported that alterations of LPA receptor expression might be important in the
      malignant transformation of tumor cells. Therefore, to assess an involvement of
      DNA methylation in reduced expression of the LPA receptor-1 (lpa1) gene, we
      investigated the expression of the lpa1 gene and its DNA methylation patterns in
      rat tumor cell lines. Both rat brain-derived neuroblastoma B103 and liver-derived
      hepatoma RH7777 cells used in this study indicated no expression of lpa1. For the
      analysis of methylation status, bisulfite sequencing was performed with B103 and
      RH7777 cells, comparing with other lpa1 expressed cells and normal tissues of
      brain and liver. The lpa1 expressed cells and tissues were all unmethylated in
      this region of lpa1. In contrast, both B103 and RH7777 cells were highly
      methylated, correlating with reduced expression of the lpa1. Treatment with 5-aza
      2'-deoxycytidine induced expression of lpa1 gene in B103 and RH7777 cells after
      24h. In RH7777 cells treated with 5-aza 2'-deoxycytidine, stress fiber formation
      was also observed in response to LPA in RH7777 cells, but not in untreated RH7777
      cells. These results suggest that aberrant DNA methylation of the lpa1 gene may
      be involved in its reduced expression in rat tumor cells.

PMID- 16970916
TI  - Quantitative evaluation of cell-to-cell communication effects in cell group class
      using on-chip individual-cell-based cultivation system.
AB  - Cell-to-cell communication is considered to underlie the coordinated behavior and
      the multicellularity of cell group class, which cannot be explained only by the
      knowledge of lower class of life system from molecule to individual cell, because
      they are determined by at least two different ways: diffusible chemical signals
      and their direct physical contacts. We show in this paper a new method of
      individual-cell-based cell observation that can estimate the role of cell-to-cell
      communication, diffusible chemical signals, and physical contacts as separated
      properties, by applying an on-chip individual-cell-based cultivation system. The
      exchange of stationary phase medium on isolated individual Escherichia coli from
      exponential phase medium and the control of physical contacts indicated that the
      cell-to-cell direct contact did not affect the growth rate; only the
      communication through diffusible signals affects the growth rates as Hill's
      equation manner.

PMID- 16970917
TI  - Crystal structure of human dynein light chain Dnlc2A: structural insights into
      the interaction with IC74.
AB  - The human light chain of the motor protein dynein, Dnlc2A, is also a novel TGF
      beta-signaling component, which is altered with high frequency in epithelial
      ovarian cancer. It is an important mediator of dynein and the development of
      cancer, owing to its ability to bind to the dynein intermediate light chain (DIC)
      IC74 and to regulate TGF-beta-dependent transcriptional events. Here we report
      the 2.1-A crystal structure of Dnlc2A using single anomalous diffraction. The
      proteins form a homodimer in solution and interact mainly through the helix
      alpha(2), strand beta(3), and the loop following this strand in each protein to
      generate a 10-stranded beta-sheet core. The surface of the beta-sheet core is
      mainly positively charged and predicted (by software PPI-Pred) to be the site
      that interacts with other partners. At the same time, the residues 79-82, 88, and
      90 of each molecule formed two holes in the core. Residue 89 of each molecule,
      which is crucial for the DIC binding function of Dnlc2A, is within the holes. On
      the basis of these observations, we propose that the homodimer is the structural
      and functional unit maintained by hydrogen bonding interactions and hydrophobic
      packing, and that the patch of the surface of the beta-sheet core is the main
      area of interaction with other partners. Furthermore, the two holes would be the
      key sites to interact with IC74.

PMID- 16970918
TI  - Expression proteomics to p53 mutation reactivation with PRIMA-1 in breast cancer
      cells.
AB  - PRIMA-1 has emerged as a small molecule that restores the wild type function to
      mutant p53. To identify molecular targets that are involved in PRIMA-1-induced
      apoptosis, we used a proteomics approach with two-dimensional gel electrophoresis
      coupled with liquid chromatography-tandem mass spectrometry for protein
      identification. By comparing the proteome of the PRIMA-1-treated MDA-231 breast
      carcinoma cells with that of MCF-7 cells, we have identified seven proteins that
      upregulated only in MDA-231 cells as a result of PRIMA-1-induced apoptosis. The
      identified proteins are involved in anaerobic glycolysis and in mitochondrial
      intrinsic apoptosis. Treatment of MDA-231 cells with PRIMA-1 resulted in the
      release of mitochondrial cytochrome c as well as the activation of caspase-3,
      which are essential for the execution of apoptosis. We present evidence to
      suggest that PRIMA-1-induced apoptosis in breast cancer cells with mutated p53
      function involved the expression of proteins required for the activation of
      mitochondrial intrinsic pathway that is glycolysis-relevant.

PMID- 16970919
TI  - Inhibitors of factor VIIa affect the interface between the protease domain and
      tissue factor.
AB  - Blood coagulation is triggered by the formation of a complex between factor VIIa
      (FVIIa) and its cofactor, tissue factor (TF). The gamma-carboxyglutamic acid-rich
      domain of FVIIa docks with the C-terminal domain of TF, the EGF1 domain of FVIIa
      contacts both domains of TF, and the EGF2 domain and protease domain (PD) form a
      continuous surface that sits on the N-terminal domain of TF. Our aim was to
      investigate the conformational changes that occur in the sTF.PD binding region
      when different types of inhibitors, i.e., one active-site inhibitor (FFR
      chloromethyl ketone (FFR)), two different peptide exosite inhibitors (E-76 and A
      183), and the natural inhibitor tissue factor pathway inhibitor (TFPI), were
      allowed to bind to FVIIa. For this purpose, we constructed two sTF mutants (Q37C
      and E91C). By the aid of site-directed labeling technique, a fluorescent label
      was attached to the free cysteine. The sTF.PD interface was affected in position
      37 by the binding of FFR, TFPI, and E-76, i.e., a more compact structure was
      sensed by the probe, while for position 91 located in the same region no change
      in the surrounding structure was observed. Thus, the active site inhibitors FFR
      and TFPI, and the exosite inhibitor E-76 have similar effects on the probe in
      position 37 of sTF, despite their differences in size and inhibition mechanism.
      The allosteric changes at the active site caused by binding of the exosite
      inhibitor E-76 in turn induce similar conformational changes in the sTF.PD
      interface as does the binding of the active site inhibitors. A-183, on the other
      hand, did not affect position 37 in sTF, indicating that the A-183 inhibition
      mechanism is different from that of E-76.

PMID- 16970920
TI  - A biphasic U-shape effect of cellular oxidative stress on the macrophage anti
      oxidant paraoxonase 2 (PON2) enzymatic activity.
AB  - Expression of macrophage paraoxonase 2 (PON2), a cellular lactonase with anti
      oxidant and anti-atherogenic properties, was shown to be upregulated under high
      oxidative stress. The aim of the present study was to analyze the relationship
      between the extent of cellular oxidative stress in J774A.1 macrophage and PON2
      lactonase activity under various levels of oxidation, obtained by cell incubation
      with either anti-oxidants or oxidants. PON2 activity exhibited a U-shape response
      curve. In the oxidative stress range below that of control untreated cells, PON2
      activity decreased upon increasing macrophage oxidative state, whereas in the
      range over that of control untreated cells, PON2 activity increased. The biphasic
      effect of oxidative stress on macrophage PON2 activity could be related to PON2
      inactivation (decreased enzymatic activity) under oxidative stress induction at
      its low range, whereas at high range of oxidative stress, macrophage anti-oxidant
      compensatory mechanism up-regulates PON2 (increased protein expression), in order
      to cope with oxidative burden.

PMID- 16970921
TI  - Effects of copper metabolism on neurological functions in Wistar and Wilson's
      disease model rats.
AB  - Behavioral functions of Wistar and Long-Evans Cinnamon (LEC) rats, Wilson's
      disease animal model, were compared by measuring the open-field, acoustic startle
      reflex and prepulse inhibition (PPI), and shuttle-box avoidance learning tests
      with or without oral supplementation with copper or D-penicillamine, copper
      chelator. All of the LEC rats, irrespective of the treatment, exhibited higher
      locomotor activity, a decreased habituation to startle response or a lower PPI,
      compared with Wistar rats. The copper content of all brain regions examined,
      except for the medulla oblongata of LEC rats, was significantly lower than those
      in Wistar rats. Besides, in the region of the striatum and the nucleus accumbens
      of the LEC rats, lower content of norepinephrine, and higher content of dopamine
      and serotonin were observed compared with Wistar rats. Although copper
      supplementation did not affect the brain copper content, it reduced the PPI in
      both Wistar and LEC rats. In contrast, D-penicillamine supplementation decreased
      both the brain copper content and locomotor activity, and enhanced the startle
      amplitude only in Wistar rats. These findings suggest that an imbalance in copper
      homeostasis affects monoamine metabolism and behavioral functions.

PMID- 16970922
TI  - Anti-angiogenesis and anti-tumor activity of recombinant anginex.
AB  - Anginex, a synthetic 33-mer angiostatic peptide, specifically inhibits vascular
      endothelial cell proliferation and migration along with induction of apoptosis in
      endothelial cells. Here we report on the in vivo characterization of recombinant
      anginex and use of the artificial anginex gene for gene therapy approaches. Tumor
      growth of human MA148 ovarian carcinoma in athymic mice was inhibited by 80% when
      treated with recombinant anginex. Histological analysis of the tumors showed an
      approximate 2.5-fold reduction of microvessel density, suggesting that
      angiogenesis inhibition is the cause of the anti-tumor effect. Furthermore, there
      was a significant correlation between the gene expression patterns of 16
      angiogenesis-related factors after treatment with both recombinant and synthetic
      anginex. To validate the applicability of the anginex gene for gene therapy,
      stable transfectants of murine B16F10 melanoma cells expressing recombinant
      anginex were made. Supernatants of these cells inhibited endothelial cell
      proliferation in vitro. Furthermore, after subcutaneous injection of these cells
      in C57BL/6 mice, an extensive delay in tumor growth was observed. These data show
      that the artificial anginex gene can be used to produce a recombinant protein
      with similar activity as its synthetic counterpart and that the gene can be
      applied in gene therapy approaches for cancer treatment.

PMID- 16970923
TI  - Differential regulation of osteoadherin (OSAD) by TGF-beta1 and BMP-2.
AB  - Osteoadherin (OSAD) is a member of the small leucine rich-repeat proteoglycan
      (SLRP) family. SLRPs are normally found in extracellular matrices, but OSAD is
      the only member restricted to mineralized tissues. We investigated the promoter
      region of OSAD by in silico analysis and found that the proximal promoter region
      contains sites for Smad-3, Smad-4, and AP-1. All are effectors of TGF-beta family
      signalling. We tested sensitivity of the promoter to the two TGF-beta family
      members TGF-beta1 and BMP-2. We found TGF-beta1 to down regulate OSAD, while BMP
      2 up regulates OSAD. As a consequence of how OSAD is regulated by TGF-beta1 and
      BMP-2 and its temporal expression pattern in osteoblasts and bone development, we
      can conclude OSAD as an early marker for terminally differentiated matrix
      producing osteoblasts.

PMID- 16970924
TI  - Probing single-stranded DNA and its biomolecular interactions through direct
      catalytic activation of factor XII, a protease of the blood coagulation cascade.
AB  - Triggered self-activation of factor XII, a blood coagulation protease, was
      utilized for the amplified visual detection of ss-DNA targets in a non-sequence
      specific way. Factor XII holds potential as a low-affinity and therefore non
      interfering probe for DNA secondary structure and for the screening of protein
      binding to ss-DNA. The observation that ss-DNA also accelerates coagulation of
      human blood plasma is relevant to the emerging field of aptamer therapeutics.

PMID- 16970925
TI  - The alternative NF-kappaB pathway from biochemistry to biology: pitfalls and
      promises for future drug development.
AB  - The past two decades have led to a tremendous work on the transcription factor NF
      kappaB and its molecular mechanisms of activation. The nuclear translocation of
      NF-kappaB is controlled by two main pathways: the classical and the alternative
      NF-kappaB pathways. The classical NF-kappaB pathway activates the IKK complex
      that controls the inducible degradation of most IkappaB family members that are
      IkappaBalpha, IkappaBbeta, IkappaBvarepsilon and p105. The alternative NF-kappaB
      pathway induces p100 processing and p52 generation through the activation of at
      least two kinases, which are NIK and IKKalpha. Genetic studies have shown that
      IKKgamma is dispensable for the alternative pathway, which suggests the existence
      of an alternative IKKalpha-containing complex. It is noteworthy that activation
      of particular p52 heterodimers like p52/RelB requires solely the alternative
      pathway while activation of p52/p65 or p52/c-Rel involves a "hybrid pathway".
      Among others, LTbetaR, BAFF-R, CD40 and RANK have the ability to induce the
      alternative pathway. The latter plays some roles in biological functions
      controlled by these receptors, which are the development of secondary lymphoid
      organs, the proliferation, survival and maturation of B cell, and the
      osteoclastogenesis. Exacerbated activation of the alternative pathway is
      potentially associated to a wide range of disorders like rheumatoid arthritis,
      ulcerative colitis or B cell lymphomas. Therefore, inhibitors of the alternative
      pathway could be valuable tools for the treatment of inflammatory disorders and
      cancers.

PMID- 16970926
TI  - Induction of G2/M phase arrest and apoptosis of human leukemia cells by potent
      antitumor triazoloacridinone C-1305.
AB  - In this study, we show that triazoloacridinone derivative C-1305, a potent
      antitumor compound, in human lymphoblastic (MOLT4) and promyelocytic (HL60)
      leukemia cells induces G2/M arrest followed by apoptosis. In both type of cells,
      C-1305 at biological relevant concentrations corresponding to EC(90) value,
      induced a significant increase in the fraction of G2/M cells. The cell cycle
      perturbations were accompanied by the appearance of sub-G1 fraction, which can be
      considered as the apoptotic cells population. In both human leukemia cells
      apoptosis was additionally proved by appearance of DNA fragmentation, activation
      of caspase-3, PARP cleavage, externalization of phosphatydilserine as well as
      decrease of the mitochondrial transmembrane potential DeltaPsi(m) and ATP
      depletion. Treatment of lymphoblastic MOLT4 cells with the C-1305 at EC(90)
      concentration, caused massive death by apoptosis. Compared to MOLT4 cells, the
      capacity of HL60 cells to execute apoptosis after C-1305 treatment at equitoxic
      dose was significantly weaker, but very effective at high concentration (4x
      EC(90)). These differences could originate from different sensitivity of both
      cell types to cytotoxic action of C-1305 (EC(50) value for MOLT4 cells was 8
      times lower than for HL60 cells and the EC(90) value was 14 times lower,
      respectively). Collectively, these results show that C-1305 is a novel and potent
      compound which induces G2/M arrest and subsequent apoptosis of human leukemia
      cells. This strong ability to induce apoptosis of tumor cells support the view
      that C-1305 could be consider as a new potent and promising antitumor agent.

PMID- 16970927
TI  - Indole-3-carbinol mediated cell cycle arrest of LNCaP human prostate cancer cells
      requires the induced production of activated p53 tumor suppressor protein.
AB  - Indole-3-carbinol (I3C), a dietary compound found naturally in cruciferous
      vegetables of the Brassica genus such as broccoli and brussels sprouts, induces a
      G1 growth arrest of human reproductive cancer cells. We previously reported that
      in LNCaP prostate cancer cells, I3C down-regulated cyclin-dependent kinase (CDK)
      2 activity. In our current study, Western blotting and quantitative RT-PCR
      demonstrated that I3C treatment increased both the transcripts and protein levels
      of the CDK2 inhibitor p21(waf1/cip1) (p21). Transfection of luciferase reporter
      plasmids containing wild-type and mutated p21 promoter fragments revealed that
      I3C induced p21 gene transcription through a p53 DNA binding element.
      Oligonucleotide precipitation showed that I3C increased the level of activated
      p53 nuclear protein that is competent to bind its DNA target site on the p21
      promoter. Ablation of p53 production using short interfering RNA (siRNA)
      prevented that the I3C induced G1 arrest and up-regulation of p21 expression.
      Western blots using p53 phospho-specific antibodies revealed that I3C treatment
      increased the levels of three phosphorylated forms of p53 (Ser15, Ser37, Ser392)
      that are known to contribute to p53 protein stability and greater transactivation
      potential. Taken together, our results establish that the I3C induced G1 arrest
      of human prostate cancer cells requires the induced production of the activated
      phosphorylated forms of p53, which stimulate transcription of the CDK2 inhibitor
      p21.

PMID- 16970928
TI  - Psychophysiological correlates of face processing in social phobia.
AB  - Social phobia has been associated with abnormal processing of angry faces, which
      directly signal disapproval--a situation that social phobics fear. This study
      investigated the electrophysiological correlates of emotional face processing in
      socially phobic and non-phobic individuals. Subjects identified either the gender
      (modified emotional Stroop task) or the expression of angry, happy, or neutral
      faces. Social phobics showed no deviations from controls in reaction times, heart
      rates, P1, or P2 amplitudes in response to angry faces, although elevated FSS
      scores were associated with higher P1 amplitudes in social phobic persons. In
      addition, social phobic persons showed enhanced right temporo-parietal N170
      amplitudes in response to angry faces in the emotion identification task.
      Furthermore, higher scores on the Social Phobia and Anxiety Inventory (SPAI) were
      associated as a trend with larger N170 amplitudes in response to angry faces in
      the emotion identification task. Thus, the present results suggest that social
      phobics show abnormalities in the early visual processing of angry faces, as
      reflected by the enhanced right-hemispheric N170 when the emotion of the angry
      face was the focus of attention, while behavioral responses and heart rates
      showed no evidence for preferred processing of angry facial expressions.

PMID- 16970930
TI  - Prolongation of alloskin graft survival by catalytic scavengers of reactive
      oxygen species.
AB  - We tested the effects of salen manganese (Salen-Mn) complexes, which are
      scavengers of reactive oxygen species exhibiting superoxide dismutase and
      catalase activities on the rejection of and alloresponse to fully allogeneic skin
      grafts in mice. We showed that pre-transplant treatment of C57Bl/6 donor skin or
      of BALB/c recipients with Salen-Mn complexes significantly delayed allograft
      rejection. ELISPOT analysis of alloimmune response of treated mice revealed a
      significant reduction of the frequency of type 1 cytokine (pro-inflammatory)
      producing T-cells, while the number of activated T-cells producing type 2
      cytokines was elevated. In addition, anti-oxidative treatment of graft recipients
      resulted in a profound inhibition of their donor-specific cytotoxic T-cell
      response. Our results indicate that salen manganese complexes mediate their
      effect on graft rejection both by reducing the susceptibility of graft tissue to
      ROS-mediated injury and by exerting an anti-inflammatory effect in recipients.

PMID- 16970929
TI  - Role of protein O-linked N-acetyl-glucosamine in mediating cell function and
      survival in the cardiovascular system.
AB  - There is growing recognition that the O-linked attachment of N-acetyl-glucosamine
      (O-GlcNAc) on serine and threonine residues of nuclear and cytoplasmic proteins
      is a highly dynamic post-translational modification that plays a key role in
      signal transduction pathways. Numerous proteins have been identified as targets
      of O-GlcNAc modifications including kinases, phosphatases, transcription factors,
      metabolic enzymes, chaperons, and cytoskeletal proteins. Modulation of O-GlcNAc
      levels has been shown to modify DNA binding, enzyme activity, protein-protein
      interactions, the half-life of proteins, and subcellular localization. The level
      of O-GlcNAc is regulated in part by the metabolism of glucose via the hexosamine
      biosynthesis pathway (HBP), and the metabolic abnormalities associated with
      insulin resistance and diabetes, such as hyperglycemia, hyperlipidemia, and
      hyperinsulinemia, are all associated with increased flux through the HBP and
      elevated O-GlcNAc levels. Increased HBP flux and O-GlcNAc levels have been
      implicated in the impaired relaxation of isolated cardiomyocytes, blunted
      response to angiotensin II and phenylephrine, hyperglycemia-induced cardiomyocyte
      apoptosis, and endothelial and vascular cell dysfunction. In contrast to these
      adverse effects, recent studies have also shown that O-GlcNAc levels increase in
      response to acute stress and that this is associated with increased cell
      survival. Thus, while the relationship between O-GlcNAc levels and cellular
      function is complex and not well-understood, it is clear that these pathways play
      a critical role in the regulation of cell function and survival in the
      cardiovascular system and may be implicated in the adverse effects of metabolic
      disease on the heart.

PMID- 16970931
TI  - Vanadium mediated apoptosis and cell cycle arrest in MCF7 cell line.
AB  - Vanadium is a metal widely distributed in the environment. It is also a dietary
      micronutrient. It has shown insulin mimetic and chemopreventive properties and
      has been considered as an important pharmacological agent. In this study, we
      evaluated the apoptogenic role of vanadium on human breast cancer cell line MCF7.
      Exposure of MCF7 cells to vanadium led to the induction of apoptosis in a dose
      dependent manner. Percentage of apoptosis was maximum (42.5%) at the highest non
      toxic dose (250 microM). It was found that vanadium treatment brought about a
      prominent chromatin condensation, cell cycle arrest leading to apoptosis. These
      apoptosis based assays demonstrate that vanadium has the potential to be
      developed into an anti-cancer drug in the near future.

PMID- 16970932
TI  - Effects of quercetin on beta-apo-8'-carotenal-induced DNA damage and cytochrome
      P1A2 expression in A549 cells.
AB  - We compared the effects of beta-carotene with those of beta-apo-8'-carotenal (AC,
      an oxidative product of beta-carotene) on DNA damage and the expression of
      cytochrome P450 (CYP)1A2 in A549 cells exposed or not to benzo[a]pyrene (BaP), a
      cigarette-associated carcinogen. Furthermore, we investigated whether quercetin,
      a flavonoid, modulates these effects. A549 cells were first preincubated with
      various concentrations of beta-carotene or AC for 1h, followed by incubation with
      20 microM BaP for 24h. Next, DNA strand breaks, measured by use of the comet
      assay, and the expression of CYP1A2, measured by use of western blotting, were
      assessed. Both beta-carotene and AC at 20 microM significantly enhanced DNA
      strand breaks and CYP1A2 expression induced by BaP. However, beta-carotene at 2
      microM significantly suppressed BaP-induced DNA strand breaks. AC alone induced
      DNA strand breaks, lipid peroxidation, and the expression of CYP1A2 in A549
      cells. The harmful effects of beta-carotene and AC on intracellular DNA were
      associated with the expression of CYP, because 1-aminobenzotriazole, a CYP
      inhibitor, partly suppressed these effects. Quercetin significantly inhibited the
      DNA strand breaks and the increase in CYP1A2 protein induced by AC or beta
      carotene in combination with BaP or by AC alone. These findings indicate that the
      harmful effect of beta-carotene induced by BaP may be through the formation of
      oxidative products such as AC. Quercetin increased the safety of high doses of
      beta-carotene, possibly through interaction with beta-carotene's oxidative
      products or through inhibition of CYP1A2 expression.

PMID- 16970933
TI  - Black rice anthocyanins inhibit cancer cells invasion via repressions of MMPs and
      u-PA expression.
AB  - Tumor metastasis is the most important cause of cancer death and various
      treatment strategies have targeted on preventing the occurrence of metastasis.
      Anthocyanins are natural colorants belonging to the flavonoid family, and are
      wildly used for their antioxidant properties. Here, we provided molecular
      evidence associated with the anti-metastatic effects of peonidin 3-glucoside and
      cyanidin 3-glucoside, major anthocyanins extracted from black rice (Oryza sativa
      L. indica), by showing a marked inhibition on the invasion and motility of SKHep
      1 cells. This effect was associated with a reduced expression of matrix
      metalloproteinase (MMP)-9 and urokinase-type plasminogen activator (u-PA).
      Peonidin 3-glucoside and cyanidin 3-glucoside also exerted an inhibitory effect
      on the DNA binding activity and the nuclear translocation of AP-1. Furthermore,
      these compounds also exerted an inhibitory effect of cell invasion on various
      cancer cells (SCC-4, Huh-7, and HeLa). Finally, anthocyanins from O. sativa L.
      indica (OAs) were evidenced by its inhibition on the growth of SKHep-1 cells in
      vivo.

PMID- 16970934
TI  - The effect of different antioxidants on glutathione turnover in human cell lines
      and their interaction with hydrogen peroxide.
AB  - BACKGROUND: Glutathione plays crucial roles in antioxidant defence and
      glutathione deficiency contributes to oxidative stress and may therefore play a
      key role in the pathogenesis of many diseases. The objectives of the present
      study were to evaluate the effects on glutathione turnover of thiol and non-thiol
      antioxidants in human cell cultures and if any of the antioxidant had a short
      term cellular effect against different levels of hydrogen peroxide. METHODS: We
      have investigated the effect on the total glutathione amount in HeLa and hepatoma
      cell cultures of thiol antioxidants in comparison with non-thiol antioxidants,
      such as a copper chelator, Vitamin C, and a flavonoid. Furthermore, we have
      investigated the short-term (within 24h) interaction of the different
      antioxidants with hydrogen peroxide. RESULTS AND CONCLUSION: Lipoic acid and
      quercetin (Quer) were the two antioxidants that showed the highest stimulation of
      glutathione synthesis in cell cultures as judged by the total glutathione amount.
      However, no antioxidant protected against hydrogen peroxide present in
      concentrations that lowered cell protein. This finding may be attributed to the
      fact that it is necessary to incubate cell cultures with antioxidants or small
      doses of oxidants for a period before the cultures are exposed to hydrogen
      peroxide in order to enhance the antioxidant defence. The presence of Quer and
      Vitamin C lowered cell protein and total glutathione even in cell cultures
      containing hydrogen peroxide in concentrations that did not lower cell protein.
      This finding might be attributed to pro-oxidant properties and formation of
      excess reactive oxygen species in the presence of Quer and Vitamin C.

PMID- 16970935
TI  - Disruption of mitochondrial redox circuitry in oxidative stress.
AB  - The present review and commentary considers oxidative stress as a disruption of
      mitochondrial redox circuitry rather than an imbalance of oxidants and
      antioxidants. Mitochondria contain two types of redox circuits, high-flux
      pathways that are central to mechanisms for ATP production and low-flux pathways
      that utilize sulfur switches of proteins for metabolic regulation and cell
      signaling. The superoxide anion radical (hereafter termed "superoxide", O2*-), a
      well known free radical product of the high-flux mitochondrial electron transfer
      chain, provides a link between the high-flux and low-flux pathways. Disruption of
      electron flow and increased superoxide production occurs due to inhibition of
      electron transfer in the high-flux pathway, and this creates aberrant "short
      circuit" pathways between otherwise non-interacting components. A hypothesis is
      presented that superoxide is not merely a byproduct of electron transfer but
      rather is generated by the mitochondrial respiratory apparatus to serve as a
      positive signal to coordinate energy metabolism. Electron mediators such as free
      Fe(3+) and redox-cycling agents, or potentially free radical scavenging agents,
      could therefore cause oxidative stress by disrupting this normal superoxide
      signal. Methods to map the regulatory redox circuitry involving sulfur switches
      (e.g., redox-western blotting of thioredoxin-2, redox proteomics) are briefly
      presented. Use of these approaches to identify sites of disruption in the
      mitochondrial redox circuitry can be expected to generate new strategies to
      prevent toxicity and, in particular, promote efforts to re-establish proper
      electron flow as a means to counteract pathologic effects of oxidative stress.

PMID- 16970936
TI  - Linguistic complexity and information structure in Korean: evidence from eye
      tracking during reading.
AB  - The nature of the memory processes that support language comprehension and the
      manner in which information packaging influences online sentence processing were
      investigated in three experiments that used eye-tracking during reading to
      measure the ease of understanding complex sentences in Korean. All three
      experiments examined reading of embedded complement sentences; the third
      experiment additionally examined reading of sentences with object-modifying,
      object-extracted relative clauses. In Korean, both of these structures place two
      NPs with nominative case marking early in the sentence, with the embedded and
      matrix verbs following later. The type (pronoun, name or description) of these
      two critical NPs was varied in the experiments. When the initial NPs were of the
      same type, comprehension was slowed after participants had read the sentence
      final verbs, a finding that supports the view that working memory in language
      comprehension is constrained by similarity-based interference during the
      retrieval of information necessary to determine the syntactic or semantic
      relations between noun phrases and verb phrases. Ease of comprehension was also
      influenced by the association between type of NP and syntactic position, with the
      best performance being observed when more definite NPs (pronouns and names) were
      in a prominent syntactic position (e.g., matrix subject) and less definite NPs
      (descriptions) were in a non-prominent syntactic position (embedded subject).
      This pattern provides evidence that the interpretation of sentences is
      facilitated by consistent packaging of information in different linguistic
      elements.

PMID- 16970937
TI  - Dutch plural inflection: the exception that proves the analogy.
AB  - We develop the view that inflection is driven partly by non-phonological analogy
      and that non-phonological information is of particular importance to the
      inflection of non-canonical roots, which in the view of [Marcus, G. F.,
      Brinkmann, U., Clahsen, H., Wiese, R., & Pinker, S. (1995). German inflection:
      the exception that proves the rule. Cognitive Psychology, 29, 189-256.] are
      inflected by a symbolic rule process. We used the Dutch plural to evaluate these
      claims. An analysis of corpus data shows that a model using non-phonological
      information (orthography) produces significantly fewer errors on plurals of non
      canonical Dutch nouns, in particular borrowings, than a model that includes only
      phonological information. Moreover, we show that a double default system, as
      proposed by Pinker [Pinker, S. (1999). Words and rules. London: Phoenix.], does
      not offer an advantage over the latter model. A second study, examining the use
      of orthography in an online plural production task, shows that, in Dutch, the
      chosen pseudoword plural is significantly affected by non-phonological
      information. A final simulation study confirms that these results are in line
      with a model of inflectional morphology that explains the inflection of non
      canonical roots by non-phonological analogy instead of by a default rule process.

PMID- 16970938
TI  - Control of mammalian oocyte growth and early follicular development by the oocyte
      PI3 kinase pathway: new roles for an old timer.
AB  - A large amount of information has accumulated over the past decade on how
      gonadotropins, steroid hormones and growth factors regulate development of the
      mammalian ovarian follicle. Moreover, the bi-directional communication between
      mammalian oocytes and their surrounding somatic (granulosa) cells has also been
      shown to be crucial for this process. The intra-ovarian factors, or more
      specifically, the intra-oocyte signaling pathways that control oocyte growth and
      early follicular development are largely unknown, however. Based on both in vitro
      studies and in vivo functional studies using gene-modified mouse models, this
      review focuses on the key features of the phosphatidylinositol 3 kinase (PI3K)
      pathway in growing mouse oocytes and on the novel functions of the oocyte PI3K
      pathway in controlling mammalian oocyte growth and follicular development that
      have come to light only recently. We propose that the PI3K pathway in the oocyte,
      which is activated by granulosa cell-produced Kit ligand (KL) via the oocyte
      surface receptor Kit, may serve as an intra-oocyte network that regulates both
      oocyte growth and the early development of ovarian follicles.

PMID- 16970939
TI  - Germ line determinants are not localized early in sea urchin development, but do
      accumulate in the small micromere lineage.
AB  - Two distinct modes of germ line determination are used throughout the animal
      kingdom: conditional-an inductive mechanism, and autonomous-an inheritance of
      maternal factors in early development. This study identifies homologs of germ
      line determinants in the sea urchin Strongylocentrotus purpuratus to examine its
      mechanism of germ line determination. A list of conserved germ-line associated
      genes from diverse organisms was assembled to search the S. purpuratus genome for
      homologs, and the expression patterns of these genes were examined during
      embryogenesis by whole mount in situ RNA hybridization and QPCR. Of the 14 genes
      tested, all transcripts accumulate uniformly during oogenesis and Sp-pumilio, Sp
      tudor, Sp-MSY, and Sp-CPEB1 transcripts are also uniformly distributed during
      embryonic development. Sp-nanos2, Sp-seawi, and Sp-ovo transcripts, however, are
      enriched in the vegetal plate of the mesenchyme blastula stage and Sp-vasa, Sp
      nanos2, Sp-seawi, and Sp-SoxE transcripts are localized in small micromere
      descendents at the tip of the archenteron during gastrulation and are then
      enriched in the left coelomic pouch of larvae. The results of this screen suggest
      that sea urchins conditionally specify their germ line, and support the
      hypothesis that this mechanism is the basal mode of germ line determination
      amongst deuterostomes. Furthermore, accumulation of germ line determinants
      selectively in small micromere descendents supports the hypothesis that these
      cells contribute to the germ line.

PMID- 16970940
TI  - Chondroitinase applied to peripheral nerve repair averts retrograde axonal
      regeneration.
AB  - Antegrade, target-directed axonal regeneration is the explicit goal of nerve
      repair. However, aberrant and dysfunctional regrowth is commonly observed as
      well. At the site of surgical nerve coaptation, axonal sprouts encounter fibrotic
      connective tissue rich in growth-inhibiting chondroitin sulfate proteoglycan that
      may contribute to misdirection of axonal regrowth. In the present study, we
      tested the hypothesis that degradation of chondroitin sulfate proteoglycan by
      application of chondroitinase at the site of nerve repair can decrease aberrant
      axonal growth. Adult rats received bilateral sciatic nerve transection and end-to
      end repair. One nerve was injected with chondroitinase ABC and the contralateral
      nerve treated with vehicle alone. After 28 weeks, retrograde axonal regeneration
      was assessed proximal to the repair by scoring neurofilament-immunopositive axons
      within the nerve (intrafascicular) and outside the nerve proper
      (extrafascicular). Intrafascicular retrograde axonal growth was equivalent in
      both control and chondroitinase treatment conditions. In contrast, chondroitinase
      treatment caused a pronounced (93%) reduction in extrafascicular retrograde
      axonal growth. The decrease in axon egress from the nerve was coincident with an
      increase in antegrade regeneration and improved recovery of motor function. Based
      on these findings, we conclude that chondroitinase applied at the site of nerve
      transection repair averts dysfunctional extrafascicular retrograde axonal growth.

PMID- 16970941
TI  - Genetic diseases of sphingolipid metabolism: pathological mechanisms and
      therapeutic options.
AB  - Although diseases in the pathway of sphingolipid degradation have been known for
      decades, the first disease in the biosynthetic pathway was only reported in 2004,
      when a form of infantile-onset symptomatic epilepsy was described as a genetic
      defect in GM3 synthase. Presumably other diseases in the sphingolipid
      biosynthetic pathway will yet be discovered, although many may remain undetected
      due to their putative lethal phenotypes. In contrast, diseases are known for
      essentially every step in the pathway of SL degradation, caused by the defective
      activity of one or other of the lysosomal hydrolases in this pathway. Despite the
      fact that some of these storage disorders were first discovered in the 19th
      century, the cellular and biochemical events that cause pathology are still
      poorly delineated. In this review, we focus on recent advances in our
      understanding of how defects in the pathways of sphingolipid metabolism may lead
      to pathology. In addition, we discuss currently-available and emerging
      therapeutic options.

PMID- 16970942
TI  - Duox2 exhibits potent heme peroxidase activity in human respiratory tract
      epithelium.
AB  - The dual oxidase isozymes Duox1 and Duox2 exhibit functional NADPH:O(2)
      oxidoreductase activity in thyroid and respiratory tract cells and are thought to
      be essential for H(2)O(2) generation in these tissues. However, it is not
      universally accepted that the heme peroxidase domains of the Duox isozymes are
      functional. To address this question, we modulated Duox2 expression in human
      tracheobronchial epithelial (TBE) cell culture systems and quantified peroxidase
      activity. We discovered that interferon-gamma (IFN-gamma) induced robust
      peroxidase activity in TBE cells that paralleled Duox2 expression. IFN-gamma
      induced peroxidase activity was abolished in the presence of sodium azide, which
      implicated the activation of a heme peroxidase. IFN-gamma-induced peroxidase
      activity was abolished in TBE cell lines expressing anti-Duox2 short hairpin RNA
      transcripts. Together, these data unequivocally demonstrated that Duox2 contains
      a functional heme peroxidase in intact respiratory tract epithelium.

PMID- 16970943
TI  - Sphingolipids in cancer: regulation of pathogenesis and therapy.
AB  - Sphingolipids are known to play important roles in the regulation of cell
      proliferation, response to chemotherapeutic agents, and/or prevention of cancer.
      Recently, significant progress has been made in the identification of the enzymes
      and their biochemical functions involved in sphingolipid metabolism. In addition,
      development of new techniques for the quantitative analysis of sphingolipids at
      their physiological levels has facilitated studies to examine distinct functions
      of these bioactive sphingolipids in cancer pathogenesis and therapy. This review
      will focus on the recent developments regarding the roles of bioactive
      sphingolipids in the regulation of cell growth/proliferation, and anti-cancer
      therapeutics.

PMID- 16970944
TI  - Transactivation of epidermal growth factor receptor by insulin-like growth factor
      1 requires basal hydrogen peroxide.
AB  - Insulin-like growth factor (IGF-1) plays an important role in prostate cancer
      development. Recent studies suggest that IGF-1 has mitogenic action through
      epidermal growth factor receptor (EGFR). However, the mechanism remains largely
      unknown. Here, we demonstrated in prostate cancer DU145 cells that IGF-1 induced
      EGFR transactivation, leading to ERK activation. Matrix metalloproteinase
      mediated shedding of heparin-binding EGF is involved in this process.
      Antioxidants and catalase inhibited IGF-1-stimulated EGFR phosphorylation,
      indicating that H(2)O(2) is required for EGFR activation. However, exogenous
      H(2)O(2) did not activate EGFR or IGF-1R in DU145 cells. IGF-1 did not induced
      production of H(2)O(2) in DU145 cells. Our results suggest that transactivation
      of EGFR by IGF-1 requires basal intracellular H(2)O(2) in DU145 cells.

PMID- 16970945
TI  - Cloning and characterization of cDNAs for hormones and/or receptors of growth
      hormone, insulin-like growth factor-I, thyroid hormone, and corticosteroid and
      the gender-, tissue-, and developmental-specific expression of their mRNA
      transcripts in fathead minnow (Pimephales promelas).
AB  - Growth hormone (GH), insulin-like growth factor-I (IGF-I), thyroid hormones, and
      corticosteroids play central roles in a wide range of body functions but, in
      fish, information on their interactions is limited. These axes of the endocrine
      system are also potential targets for disruption of signaling pathways by hormone
      mimicking chemicals, but have received little study. Molecular approaches offer
      an effective way to help unravel these endocrine interactions but require the
      appropriate gene-specific assays to do so. In this study, the cDNAs for a suite
      of hormones and/or receptors involved in signaling for the effects of GH and IGF
      I [GH, GH receptor (GHR), IGF-I, IGF-I receptor (IGF-IR)], thyroid hormones
      [thyroid hormone receptor alpha (TRalpha) and beta (TRbeta)], and corticosteroids
      [glucocorticoid receptor (GR)] were cloned from the fathead minnow (Pimephales
      promelas; fhm), and the tissue-, developmental-, and gender-related expression of
      their mRNA transcripts established. By polymerase chain reaction (PCR) strategy,
      we obtained full-length 1123-bp GH, 817-bp IGF-I, 1584-bp TRbeta, and 2571-bp GR
      cDNAs, coding for 210 amino acid (aa) GH, 161 aa IGF-I, 378 aa TRbeta, and 745 aa
      GR putative proteins, and partial-length 158-bp GHR, 811-bp IGF-IR, and 446-bp
      TRalpha cDNAs. Real-time PCR analyses revealed broad tissue expression for the
      target mRNAs; all targets were expressed in brain, pituitary, gill, liver, gonad,
      intestine, and muscle, with the exception of GH that was expressed only in the
      pituitary and gonad. Expression patterns in both juvenile and adult fhm were
      complex, with both temporal-, tissue-, and sex-specific characteristics. For
      example, hepatic expressions of GHR, IGF-I, and IGF-IR were far higher in males
      than in females, possibly reflecting the sex-related dimorphism in growth that
      occurs in this species, and TRalpha and TRbeta showed divergent expression
      patterns during development (where TRbeta predominated) and in adult tissues
      implying some distinct roles for the two TR subtypes.

PMID- 16970946
TI  - Can lessons be learned from history? The origins of the British imperial nurse
      labour market: a discussion paper.
AB  - The British government's involvement in overseas nurse recruitment originated in
      its imperial past when the Colonial Nursing Service was established in 1940 by
      the Colonial Office to unify the administration of British nurse appointments
      across the Empire. The Colonial Office unified recruitment arrangements for
      colonial nursing posts, effectively creating an imperial market in nursing
      labour, which arguably set the historical precedent for the greater flow of
      international nurse recruitment from and to the United Kingdom (UK). The recent
      implementation of the Nursing and Midwifery Council's Overseas Nurses Programme
      to regulate the registration route for international nurse recruits to the UK is
      symptomatic of growing international nurse migration. In a globalising
      marketplace, overseas nurse recruitment remains a significant supply factor in
      meeting the staffing needs of the National Health Service (NHS) in the UK. The
      continuities between the historical case of the Colonial Nursing Service and the
      current prevalence of transnational nurse migration highlight a pervading tension
      between the professional agenda of nursing and recruiters' and governments'
      responses to market pressures.

PMID- 16970947
TI  - In vivo coronary plaque histology in patients with stable and acute coronary
      syndromes: relationships with hyperlipidemic status and statin treatment.
AB  - OBJECTIVES: Aim of the study was to investigate whether maintained moderate
      statin treatment influence atheroma, macrophage content, neoangiogenesis and/or
      haemorrhage in coronary plaques from patients with non-fatal coronary syndromes.
      METHODS: A total of 48 patients underwent elective directional coronary
      atherectomy on "de novo" culprit lesions; 16 patients had non-treated
      hypercholesterolemia, 16 patients received maintained moderate statin treatment
      for hypercholesterolemia and 16 had no lipoprotein abnormalities. These three
      patients groups were matched for age and clinical diagnosis of stable angina (SA)
      or unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI).
      Atherectomy specimens were stained with antibodies against macrophages,
      endothelial cells and glycophorin A. Results of histology and
      immunohistochemistry were morphometrically analyzed by using computer-assisted
      image analysis. RESULTS: Atheroma and fibrous tissue, neoangiogenesis, macrophage
      and haemorrhage (i.e., glycophorin A) differed between the three groups (P<0.05).
      Statin-treated group showed significantly decreased atheroma (P=0.016), fibrous
      tissue (P=0.42), macrophage content (P=0.012), neoangiogenesis (P=0.00048) and
      haemorrhage (P=0.0092) as compared with the non-treated hyperlipidemic group.
      CONCLUSIONS: The present findings show that maintained moderate statin treatment
      may contribute to plaque stabilization in non-fatal coronary syndromes by
      decreasing intraplaque neoangiogenesis and haemorrhage, lipid burden and
      macrophage content, and, on the other hand, by increasing plaque collagenization.

PMID- 16970948
TI  - A green tea extract lowers plasma cholesterol by inhibiting cholesterol synthesis
      and upregulating the LDL receptor in the cholesterol-fed rabbit.
AB  - Green tea extracts enriched in catechins decrease plasma cholesterol in hamsters,
      mice and rats. The aims of this study were to determine whether a catechin
      enriched extract of green tea could lower plasma cholesterol in the cholesterol
      fed rabbit and to determine the mechanism of action. Four groups of six New
      Zealand White rabbits were initially made hypercholesterolaemic by feeding a
      0.25% (w/w) cholesterol diet for 2 weeks before the diet was supplemented with a
      catechin extract from green tea at 0, 0.5, 1 or 2% (w/w) for 4 weeks.
      Administration of the crude catechin extract from green tea significantly
      (p<0.05) lowered cholesterol in plasma (-60%), VLDL+IDL (-70%), LDL (-80%), liver
      (total by -25% and unesterified by -15%) and aorta (-25%) compared to control.
      There was a significant reduction in the cholesterol synthesis index (-60%) and a
      significant increase in hepatic LDL receptor activity (+80%) and protein (+70%)
      but there was no change in the intrinsic capacity to absorb cholesterol from the
      intestines. These results suggest that green tea catechins lowered plasma, liver
      and aortic cholesterol in the cholesterol-fed rabbit by lowering cholesterol
      synthesis and upregulating the hepatic LDL receptor.

PMID- 16970949
TI  - Hyperhomocysteinemia in patients with symptomatic chronic heart failure:
      prevalence and prognostic importance--pilot study.
AB  - BACKGROUND: Patients with chronic heart failure (CHF) may be particularly
      susceptible to unfavorable effects of hyperhomocysteinemia (HHcy). The aim of
      this study was to assess the prevalence of HHcy (plasma homocysteine [Hcy]>or=14
      micromol/L) in an unselected cohort of CHF patients, its clinical determinants,
      and prognostic implications. METHODS AND RESULTS: In 108 consecutive CHF patients
      (81 men, age: 66+/-11 years) with mean plasma Hcy level 12.5+/-5.5 micromol/L
      (range 2.3-28.3 micromol/L), 38 (35%) patients demonstrated HHcy. Among clinical
      and metabolic parameters, in multivariable regression models, advanced NYHA class
      (P<0.0001), plasma NT-proBNP (P<0.001), peak oxygen consumption (P<0.05), reduced
      glomerular filtration rate (P<0.0001) and elevated serum uric acid (P<0.05)
      predicted high plasma Hcy level. HHcy was related to increased mortality
      (HR=3.26, 95% CI: 1.78-5.98, P=0.0001), also when adjusted for conventional
      prognosticators in multivariable models (all P<0.01). In patients with HHcy, a 3
      year survival was 37% (95% CI: 22-52%) as compared to 73% (95% CI: 63-83%) in
      those with normal Hcy levels (P<0.0001). CONCLUSIONS: HHcy is common in CHF, is
      related to the disease severity, depicts generalized metabolic imbalance
      (evidenced by hyperuricaemia), and independently predicts poor long-term
      prognosis.

PMID- 16970950
TI  - AT1-receptor blockade with irbesartan improves peripheral but not coronary
      endothelial dysfunction in patients with stable coronary artery disease.
AB  - Activation of the renin-angiotensin-aldosterone system plays an important role in
      the pathogenesis of endothelial dysfunction and atherosclerosis. Studies
      evaluating the effect of AT1-receptor blockers on endothelial dysfunction in
      patients with coronary artery disease (CAD) revealed mixed results. Studies
      addressing the effects of AT1-receptor blockers on the coronary and peripheral
      function in the same study population, are still lacking. We therefore aimed to
      test the effects of long-term therapy with the AT1-receptor blocker irbesartan
      (IRB) on both, the coronary and peripheral endothelial function in patients with
      CAD. Seventy-two patients with CAD were randomly assigned to double-blinded
      treatment for 6 months with IRB 300 mg per day or placebo, respectively. Coronary
      and peripheral endothelial function were measured by intracoronary infusion of
      acetylcholine (final intracoronary concentration 10(-7.3) to 10(-5.6)M) and by
      determining flow-dependent dilation (FMD) of the brachial artery, respectively.
      IRB significantly improved FMD, while no change of coronary endothelial function
      was observed. Interestingly, plasma levels of N(G),N(G)-dimethyl-arginine, and
      the isoprostane excretion rate were not modified. IRB treatment improves
      peripheral but not coronary endothelial dysfunction in patients with CAD. Since
      reduced FMD of the brachial artery has been shown to be associated with a high
      cardiovascular event rate, improvement of FMD by IRB may lead to better prognosis
      of patients with CAD.

PMID- 16970951
TI  - Non-alcoholic fatty liver disease and increased risk of cardiovascular disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is present in up to one-third of the
      general population and in the majority of patients with cardio-metabolic risk
      factors such as abdominal obesity, type 2 diabetes and other components of the
      metabolic syndrome (MetS). Currently, the importance of NAFLD and its
      relationship to the MetS is increasingly recognized, and this has stimulated an
      interest in the possible role of NAFLD in the development of cardiovascular
      disease (CVD). Indeed, the impact of NAFLD on CVD risk deserves particular
      attention in view of the implications for screening/surveillance strategies in
      this growing number of patients. Recent evidence suggests that the severity of
      liver histology in NAFLD patients is closely associated with markers of early
      atherosclerosis such as greater carotid artery wall thickness and lower
      endothelial flow-mediated vasodilation independently of classical risk factors
      and components of the MetS. Moreover, NAFLD is associated with greater overall
      mortality and independently predicts the risk of future CVD events. Overall, the
      current body of evidence strongly suggests that NAFLD is likely to be associated
      with increased CVD risk, and raises the possibility that NAFLD may be not only a
      marker but also an early mediator of atherosclerosis.

PMID- 16970952
TI  - Long-term effect of bezafibrate on pancreatic beta-cell function and insulin
      resistance in patients with diabetes.
AB  - OBJECTIVE: Development of insulin resistance (IR) and the progressive failure of
      the pancreatic beta-cell function (BCF) may be important in the pathogenesis of
      type 2 diabetes. Influence of peroxisome proliferator-activated receptors ligand
      bezafibrate on BCF and IR in patients with diabetes is unknown. The present study
      was aimed to investigate the long-term effect of bezafibrate on these parameters
      in diabetic patients enrolled in the Bezafibrate Infarction Prevention (BIP)
      Study. METHODS: Metabolic and inflammatory parameters were analyzed from stored
      frozen plasma samples obtained from 351 diabetic patients (168 treated by
      bezafibrate and 183 by placebo) who completed a 2-year of randomized, double
      blind, placebo-controlled study period. The homeostatic indexes of BCF (HOMA-BCF)
      and IR (HOMA-IR) were calculated according to the homeostasis model of
      assessment. RESULTS: Both groups displayed similar baseline characteristics.
      During follow-up, in the placebo group there was 28% rise of HOMA-IR (p<0.001).
      In contrast, HOMA-IR in patients in the bezafibrate group did not change
      (p=0.99). The intergroup differences in HOMA-IR percentage changes were in favor
      of bezafibrate (p=0.01). HOMA-BCF values have significantly decreased by 13.9%
      (p=0.04) in patients of placebo group, whereas in patients of bezafibrate group
      HOMA-BCF was stable during follow-up and its alterations (-2.9%) were non
      significant (p=0.59). CONCLUSIONS: Diabetic patients from the placebo group
      demonstrated a progressive declining of BCF and an increasing of IR over 2 years
      of follow-up. These longitudinal changes were attenuated when patients used
      bezafibrate.

PMID- 16970953
TI  - Future adverse cardiac events can be predicted by persistently low plasma
      adiponectin concentrations in men and marked reductions of adiponectin in women
      after acute myocardial infarction.
AB  - There is conflicting information about whether mortality after AMI is higher in
      women than men. We investigated the significance of plasma adiponectin
      concentrations on major adverse cardiac events (MACE) after acute myocardial
      infarction (AMI) to delineate any differences between men and women. The study
      patients consisted of 114 men and 42 women with AMI. The incidence of MACE was
      significantly higher in women than men during the entire follow-up period
      (p<0.05). Compared with men for post-AMI MACE, the hazard ratio for women was 5.6
      after adjustment for prognostic factors. Killip class (p<0.001) and sex
      differences (p<0.05) were independent predictors of MACE at 1 year post-AMI.
      Plasma adiponectin levels in women were significantly higher than men on
      admission (8.66 microg/mL [range: 6.6-14.08] versus 4.71 microg/mL [range: 3.47
      7.27], p<0.0001) and during the post-AMI course (all p<0.0001). Multivariate
      analysis identified plasma adiponectin level on admission as an independent
      predictor of MACE in men (p<0.001) and the difference between plasma adiponectin
      levels at discharge and on admission in women (p<0.05). Patterns of serial
      changes in plasma adiponectin concentrations are different between men and women
      and plasma adiponectin concentrations can be used to predict future adverse
      cardiac events in AMI patients.

PMID- 16970954
TI  - Serum total cholesterol levels and risk of mortality from stroke and coronary
      heart disease in Japanese: the JACC study.
AB  - The relation between serum total cholesterol and coronary heart disease is well
      established, but the relations with total stroke and stroke subtypes are
      controversial. We conducted a nested case-control study as part of the JACC
      study. A total of 39,242 subjects, 40-79 years of age, provided serum samples at
      baseline between 1988 and 1990. During the 10-year follow-up, 345 deaths from
      total strokes (including 76 intraparenchymal hemorrhages) and 150 deaths from
      coronary heart diseases were recorded. The control subjects were matched for sex,
      age, community, and year of serum storage, and further adjusted for systolic
      blood pressure, high density lipoprotein (HDL)-cholesterol, ethanol intake
      category, smoking status, and diabetes. Serum total cholesterol levels were
      measured using an enzymatic method. Cases with total stroke and more specifically
      intraparenchymal hemorrhage had lower mean values of serum total cholesterol
      levels compared with control subjects. The risk of mortality from
      intraparenchymal hemorrhage was significantly higher for persons with low total
      cholesterol levels [less than 4.14 mmol/l (160 mg/dl)] than with those with
      higher levels. The risk of mortality from coronary heart disease for persons with
      serum total cholesterol levels more than or equal to 6.72 mmol/l (260 mg/dl) was
      significantly higher than those with levels less than 4.14 mmol/l (160 mg/dl).
      Low serum total cholesterol levels are associated with high mortality from
      intraparenchymal hemorrhage while high levels are associated with high mortality
      from coronary heart disease among Japanese.

PMID- 16970955
TI  - Ethanol beverages containing polyphenols decrease nuclear factor kappa-B
      activation in mononuclear cells and circulating MCP-1 concentrations in healthy
      volunteers during a fat-enriched diet.
AB  - AIMS: Different epidemiological studies have demonstrated that some ethanol
      containing beverages intake could be associated with a reduction of
      cardiovascular mortality, effect attributed in part to its antioxidant
      properties. Nuclear factor-kappa B (NF-kappaB) is a redox sensitive transcription
      factor implicated in the pathogenesis of atherosclerosis. We have examined the
      effect of four different ethanol containing beverages on the activation of NF
      kappaB in peripheral blood mononuclear cells (PBMC) and circulating
      concentrations of monocyte chemoattractant protein-1 (MCP-1) in healthy
      volunteers receiving a fat-enriched diet. METHODS AND RESULTS: Sixteen volunteers
      received 16 g/m(2) of ethanol in form of red wine, spirits (vodka, rum, and
      brandy) or no ethanol intake along with a fat-enriched diet during 5 days and all
      of them took all alcohols at different periods. NF-kappaB activation
      (electrophoretic mobility shift assay) and circulating MCP-1 levels (ELISA) were
      examined in blood samples taken before and after 5 days of ethanol intake.
      Subjects receiving a fat-enriched diet had increased NF-kappaB activation in PBMC
      at day 5. Furthermore, MCP-1 levels were increased in plasma at day 5. Red wine
      intake and some ethanol beverages containing polyphenols (brandy and rum)
      prevented NF-kappaB activation and decreased MCP-1 release. CONCLUSION:
      Consumption of moderate amounts of alcoholic drinks containing polyphenols
      decreases NF-kappaB activation in PBMCs and MCP-1 plasma levels during a fat
      enriched diet. Our results provide additional evidence of the anti-inflammatory
      effects of some ethanol containing beverages, further supporting the idea that
      its moderate consumption may help to reduce overall cardiovascular mortality.

PMID- 16970956
TI  - Connexin37 1019 gene polymorphism in myocardial infarction patients and
      centenarians.

PMID- 16970958
TI  - A microplate solid scintillation counter as a radioactivity detector for high
      performance liquid chromatography in drug metabolism: validation and
      applications.
AB  - Sensitive radioactivity detection following high performance liquid
      chromatography (HPLC) separation remains a challenge in many drug metabolism
      studies with radiolabeled compounds. In this work, solid scintillation counting
      (SSC) after fraction collection into 96-well plates was evaluated as an off-line
      radioactivity detection method, in comparison with conventional liquid
      scintillation counting (LSC). The impact of counting time and biological matrix
      on the quantification of radiolabeled metabolites and parent drug in samples from
      animal and human absorption, distribution, metabolism and excretion (ADME)
      studies was investigated. Three different approaches were used to test whether
      reliable quantification by off-line SSC detection, which requires an
      approximately constant counting yield during the entire chromatographic run, can
      be realized: (i) the measurement of radioactivity-spiked biological blank samples
      without HPLC separation as an extreme case of biological background, (ii) the
      measurement of radioactivity-spiked HPLC fractions of biological blank samples
      and (iii) the comparison of radiochromatograms obtained by off-line SSC and LSC
      of real samples from ADME studies with radiolabeled compounds. Situations in
      which variations in SSC yield during an HPLC run are likely to lead to
      significant errors in quantitation were identified and are discussed. However,
      examples from a number of animal or human ADME studies showed that in the
      majority of cases off-line SSC provides very similar quantitative data, compared
      with the reference method of off-line LSC radioactivity detection. Approaches for
      validation of the off-line SSC approach in critical cases are discussed. The main
      advantages of off-line SSC, compared with off-line LSC, are lower detection
      limits and a substantially higher throughput. Several applications of off-line
      SSC detection in ADME studies are shown.

PMID- 16970959
TI  - Quantification and confirmation of anionic, cationic and neutral pesticides and
      transformation products in water by on-line solid phase extraction-liquid
      chromatography-tandem mass spectrometry.
AB  - Two on-line SPE-LC-ESI-MS/MS methods have been developed for the rapid
      determination and confirmation of 18 polar pesticides and nine transformation
      products (TPs) in water samples. Given the very different physico-chemical
      characteristics of the analytes, it was not feasible the simultaneous
      determination of all selected compounds in only one method. Thus, it was
      necessary to use heptafluorobutyric acid and formic acid in order to obtain good
      retention in the SPE cartridge for basic and acidic analytes, respectively. The
      developed analytical methodology based on the direct injection of 2 mL of water
      sample in the system allowed the quantification of all analytes at the 25 ng/L
      level (LOQ) with limits of detection normally lower than 5 ng/L. Satisfactory
      recoveries (70-110%) were obtained for most compounds in ground and surface water
      samples. Some exceptions were found mainly in surface water, due to the ion
      suppression produced by the higher amount of matrix interferents in these
      samples. The acquisition of two MS/MS transitions for each compound allowed the
      reliable confirmation of positive findings even at the LOQ level. The developed
      methodology was applied to real ground and surface water samples showing the
      interest of including TPs in monitoring methods, as several of them were found at
      concentrations higher than that of parent compounds.

PMID- 16970960
TI  - Determination of diastereomerization barrier of some flavanones by high
      performance liquid chromatography methods.
AB  - The rate constants and activation energy barriers DeltaG# of diastereomerization
      reaction of flavanones: naringin, narirutin, hesperidin and neohesperidin were
      determined. The stopped-flow HPLC (SFM-HPLC), dynamic HPLC (D-HPLC) and
      enantioselective HPLC combined with the classical kinetic method were applied for
      determination of these parameters. It was found that the rate constants of
      diastereomerization were about eight times higher for naringin and narirutin (1.9
      x 10(-5) s(-1)) than for hesperidin and neohesperidin (2.4 x 10(-6) s(-1)). No
      significant differences in the rate of diastereomerization were found between
      neohesperidosides and corresponding rutinosides.

PMID- 16970961
TI  - Use of solid-phase microextraction to detect and quantify gas-phase dicarbonyls
      in indoor environments.
AB  - Solid-phase microextraction (SPME) was evaluated for the detection and
      quantification of the gas-phase dicarbonyls, glyoxal (GLY) and methylglyoxal
      (MGLY). Additionally, polydimethylsiloxane (PDMS),
      polydimethylsiloxane/divinylbenzene (PDMS/DVB), and carbowax/divinylbenzene
      (CW/DVB) fibers were tested to determine the optimum fiber for detection of these
      species. GLY and MGLY were derivatized with O-(2,3,4,5,6-pentafluorobenzyl)
      hydroxylamine hydrochloride (PFBHA), extracted with SPME from headspace or bag
      chamber and then analyzed by GC/MS. The PDMS/DVB SPME fiber for on-fiber
      derivatization and subsequent sampling for gas-phase methylglyoxal provided the
      optimum combination of analytical reproducibility and sensitivity. Linearity of
      the calibration curve was achieved across a range of 11-222 microg/m(3) (4-75
      ppb).

PMID- 16970962
TI  - Interactions of L-arginine with Langmuir monolayers of di-n-dodecyl hydrogen
      phosphate at the air-water interface.
AB  - The surface phase behavior of di-n-dodecyl hydrogen phosphate (DDP) in Langmuir
      monolayer and its interactions with L-arginine (L-arg) have been investigated by
      measuring pi-A isotherms with a film balance and observing monolayer morphology
      with a Brewster angle microscopy (BAM). The DDP monolayers on pure water show a
      first-order liquid expanded-liquid condensed (LE-LC) phase transition and form
      fingering LC domains having uniform brightness at different temperatures. At 15
      degrees C, the pi-A isotherms on pure water and on different concentration
      solutions of L-arg show a limiting molecular area at approximately 0.50
      nm(2)/molecule. With increasing the subphase concentration of L-arg up to 4.0 x
      10(-4)M, the LE and the LE-LC coexistence regions shift to larger molecular areas
      and higher surface pressures, respectively. With a further increase in the
      concentration of L-arg beyond this critical concentration, these isotherms show
      little or no more expansion. These results have been explained by considering the
      fact that the L-arg undergoes complexation with the DDP to form L-arg-DDP that
      remains in equilibrium with the components at the air-water interface. As the
      concentration of L-arg in the subphase increases, the equilibrium shifts towards
      the complex. At a concentration of L-arg > or =4.0 x 10(-4)M, the DDP monolayers
      get saturated and show the characteristics of the new amphiphile, L-arg-DDP. BAM
      is applied to confirm the above results. When the concentration of the L-arg is
      <4.0 x 10(-4)M, domains always start forming at an area of approximately 0.64
      nm(2)/molecule, which is the critical molecular area for the phase transition in
      the DDP monolayers on pure water. In contrast, when the monolayers are formed on
      a solution containing > or =4.0 x 10(-4)M L-arg, comparatively smaller size
      domains are formed after the appearance of a new cusp point at approximately 0.55
      nm(2)/molecule. With an increase in the concentration of L-arg in the subphase,
      the size of the domains decreases indicating that the fraction of the DDP
      gradually decreases, whereas the fraction of the complex gradually increases. In
      addition, a very simple procedure for determination of the stability constant,
      which is 2.6 x 10(4)M(-1) at 15 degrees C, has been suggested.

PMID- 16970963
TI  - Quantitative analysis of complement receptors, CR1 (CD35) and CR3 (CD11b), on
      neutrophils improves distinction between bacterial and viral infections in
      febrile patients: comparison with standard clinical laboratory data.
AB  - There is an ongoing need for sensitive and specific markers of bacterial
      infection. In this prospective study, standard clinical laboratory data
      (neutrophil count, serum C reactive protein level, erythrocyte sedimentation
      rate) and quantitative flow cytometric analysis of neutrophil complement
      receptors, CR1 and CR3, were obtained from 289 hospitalized febrile patients.
      After microbiological confirmation or clinical diagnosis, 135 patients were found
      to have either bacterial (n = 89) or viral (n = 46) infection. The patient data
      was compared to 60 healthy controls. In bacterial infections, all measured
      variables were significantly increased, particularly the average amounts of CR1
      and CR3 on neutrophils were over three-fold and two-fold higher, respectively,
      compared to viral infections and controls. We described a novel marker of local
      and systemic bacterial infections designated 'clinical infection score (CIS)
      point', which incorporates quantitative analysis of complement receptors on
      neutrophils and standard clinical laboratory data. CIS point varied between 0 and
      8, and displayed 98% sensitivity and 97% specificity in distinguishing between
      bacterial and viral infections [average (S.D.); CIS points: 6.2 (1.7) vs. 0.6
      (1.0); p < 0.001]. These findings suggest that the proposed CIS-based diagnostic
      test could potentially assist physicians in deciding whether antibiotic treatment
      is necessary.

PMID- 16970964
TI  - Binding-induced stabilization and assembly of the phage P22 tail accessory factor
      gp4.
AB  - To infect and replicate, bacteriophage P22 injects its 43 kbp genome across the
      cell wall of Salmonella enterica serovar Typhimurium. The attachment of phage P22
      to the host cell as well as the injection of the viral DNA into the host is
      mediated by the virion's tail complex. This 2.8 MDa molecular machine is formed
      by five proteins, which include the portal protein gp1, the adhesion tailspike
      protein gp9, and three tail accessory factors: gp4, gp10, gp26. We have isolated
      the tail accessory factor gp4 and characterized its structure and binding
      interactions with portal protein. Interestingly, gp4 exists in solution as a
      monomer, which displays an exceedingly low structural stability (Tm 34 degrees
      C). Unfolded gp4 is prone to aggregation within a narrow range of temperatures
      both in vitro and in Salmonella extracts. In the virion the thermal unfolding of
      gp4 is prevented by the interaction with the dodecameric portal protein, which
      stabilizes the structure of gp4 and suppresses unfolded gp4 from irreversibly
      aggregating in the Salmonella milieu. The structural stabilization of gp4 is
      accompanied by the concomitant oligomerization of the protein to form a ring of
      12 subunits bound to the lower end of the portal ring. The interaction of gp4
      with portal protein is complex and likely involves the distinct binding of two
      non-equivalent sets of six gp4 proteins. Binding of the first set of six gp4
      equivalents to dodecameric portal protein yields a gp(1)12:gp(4)6 assembly
      intermediate, which is stably populated at 30 degrees C and can be resolved by
      native gel electrophoresis. The final product of the assembly reaction is a bi
      dodecameric gp(1)12:gp(4)12 complex, which appears hollow by electron microscopy,
      suggesting that gp4 does not physically plug the DNA entry/exit channel, but acts
      as a structural adaptor for the other tail accessory factors: gp10 and gp26.

PMID- 16970965
TI  - Amygdala damage impairs emotion recognition from music.
AB  - The role of the amygdala in recognition of danger is well established for visual
      stimuli such as faces. A similar role in another class of emotionally potent
      stimuli -- music -- has been recently suggested by the study of epileptic
      patients with unilateral resection of the anteromedian part of the temporal lobe
      [Gosselin, N., Peretz, I., Noulhiane, M., Hasboun, D., Beckett, C., & Baulac, M.,
      et al. (2005). Impaired recognition of scary music following unilateral temporal
      lobe excision. Brain, 128(Pt 3), 628-640]. The goal of the present study was to
      assess the specific role of the amygdala in the recognition of fear from music.
      To this aim, we investigated a rare subject, S.M., who has complete bilateral
      damage relatively restricted to the amygdala and not encompassing other sectors
      of the temporal lobe. In Experiment 1, S.M. and four matched controls were asked
      to rate the intensity of fear, peacefulness, happiness, and sadness from computer
      generated instrumental music purposely created to express those emotions.
      Subjects also rated the arousal and valence of each musical stimulus. An error
      detection task assessed basic auditory perceptual function. S.M. performed
      normally in this perceptual task, but was selectively impaired in the recognition
      of scary and sad music. In contrast, her recognition of happy music was normal.
      Furthermore, S.M. judged the scary music to be less arousing and the peaceful
      music less relaxing than did the controls. Overall, the pattern of impairment in
      S.M. is similar to that previously reported in patients with unilateral
      anteromedial temporal lobe damage. S.M.'s impaired emotional judgments occur in
      the face of otherwise intact processing of musical features that are emotionally
      determinant. The use of tempo and mode cues in distinguishing happy from sad
      music was also spared in S.M. Thus, the amygdala appears to be necessary for
      emotional processing of music rather than the perceptual processing itself.

PMID- 16970966
TI  - Role of ferutinin in the impairment of female sexual function induced by Ferula
      hermonis.
AB  - In the present study, we evaluated the effects of single components of Ferula
      hermonis extract on female rat sexual behaviour. Ovariectomized rats hormonally
      primed with estradiol benzoate (1.5 or 10 microg/rat s.c.) and progesterone (500
      microg/rat s.c.) were acutely treated by oral gavage with ferutinin, teferin and
      teferdin (2.5 mg/kg). Thereafter they were tested for: a) partner preference, b)
      receptivity, c) proceptivity, d) paced mating behaviour. In the partner
      preference test, the choice of the female for a sexually active male was not
      influenced by the different treatments. Similarly, during the paced mating test,
      the contact-return latencies as well as the percentage of exits from the male
      compartment were not different in control and treated rats. Therefore none of the
      three compounds showed the capacity to alter sexual motivation. On the other
      hand, ferutinin, but not teferin and teferdin, significantly inhibited female
      receptivity. These results suggest a primary role of ferutinin in the impairment
      of sexual behaviour elicited by F. hermonis extract in hormone primed-female
      rats.

PMID- 16970967
TI  - Synthesis of steroidal lactone by penicillium citreo-viride.
AB  - The biotransformations of a series of steroids by the fungus penicillium citreo
      viride A.C.C.C. 0402 have been investigated, and the conversion to the same
      product testolactone (1) was observed from progesterone (2),
      dehydroepiandrosterone (3), 4-androstene-3, 17-dione (4), 5-androstene-3, 17-diol
      (5) with the exception of pregnenolone (6) and 3beta-hydroxy-5, 16-pregnadien-20
      one (7). The possible metabolic pathways of the biotransformations were also
      discussed in the paper and the fungus penicillium citreo-viride A.C.C.C. 0402 was
      isolated during screening stains from samples collected from Zhengzhou, Henan
      province of China.

PMID- 16970968
TI  - Exact and approximate analysis of surface acoustic waves in an infinite elastic
      plate with a thin metal layer.
AB  - For an accurate approximation of the effect of a thin layer over a finite
      substrate, we consider the displacements are continuous across the interface,
      while the stress components are obtained from derivatives of displacements. As a
      result, the stress boundary conditions are transformed to a relationship between
      stresses in the vicinity of the interface of two layers and density of the metal
      layer. Through this approximation, we eventually have four equations to solve for
      the surface acoustic wave dispersion relation of the two-layer structure. The
      approximate and accurate results are compared with good agreement for small
      thickness of the metal layer. These results are intended for periodic structures
      with separate solutions for electroded and unelectroded regions, which can be
      connected by the continuity boundary conditions for the analysis of the complete
      structure of typical surface acoustic wave resonators.

PMID- 16970969
TI  - Design and experiment on a mini cascade thermoacoustic engine.
AB  - A miniature cascade thermoacoustic engine had been designed and tested, which
      length was about 1m, operating at 500 Hz. Pilot study and experimental results
      shown a rather good agreement between measured and calculated pressure fields and
      temperatures distributions in the thermoaoustic engine. The peak-to-peak value of
      the acoustic pressure was 0.02 MPa at the 1.8 MPa charged pressure of helium.
      Some efforts had been made to extend the traveling-wave region based on the
      analysis of the acoustic impedance.

PMID- 16970970
TI  - Rapid ecotoxicological bioassay using delayed fluorescence in the green alga
      Pseudokirchneriella subcapitata.
AB  - A rapid and simple ecotoxicological bioassay allows quick estimation of the
      effects of Simazine (CAT) or 3,5-dichlorophenol (3,5-DCP) on the growth of the
      green alga Pseudokirchneriella subcapitata (formerly Selenastrum capricornutum).
      The effects of a 15-min exposure to CAT or 3,5-DCP on delayed fluorescence (DF)
      in P. subcapitata were compared to the results of standard growth inhibition
      tests involving 72h of exposure to these chemicals at the same concentrations.
      Integrated DF intensity in the time period from 0.6 to 50s was found to correlate
      with algal growth inhibition as measured by the standard tests. In addition, the
      behaviour of DF in this time period exhibited characteristic kinetics indicative
      of the chemical being tested.

PMID- 16970971
TI  - Cometabolism of trihalomethanes by mixed culture nitrifiers.
AB  - Three mixed-culture nitrifier sources degraded low concentrations (25-450
      microg/L) of four trihalomethanes (THMs) (trichloromethane (TCM) or chloroform,
      bromodichloromethane (BDCM), dibromochloromethane (DBCM), tribromomethane (TBM)
      or bromoform) commonly found in treated drinking water. Individual THM rate
      constants (k1THM) increased with increasing THM bromine-substitution with
      TBM>DBCM>BDCM>TCM and were comparable to previous studies with the pure culture
      nitrifier, Nitrosomonas europaea. A decrease in temperature resulted in a
      decrease in both ammonia and THM degradation rates with ammonia rates affected to
      a greater extent than THM degradation rates. The significant effect of
      temperature indicates that seasonal variations in water temperature should be a
      consideration for technology implementation. Product toxicity, measured by
      transformation capacity (T(c)), was similar to that observed with N. europaea.
      Because both rate constants and product toxicities increase with increasing THM
      bromine-substitution, a water's THM speciation is an important consideration for
      process implementation during drinking water treatment. Even though a given water
      is kinetically favored, the resulting THM product toxicity may not allow stable
      treatment process performance.

PMID- 16970972
TI  - Metal-doped carbon aerogels as catalysts during ozonation processes in aqueous
      solutions.
AB  - The efficiency of Co(II)-, Mn(II)-, and Ti(IV)-doped carbon aerogels for the
      transformation of ozone into (*)OH radicals was investigated. The carbon aerogels
      had a markedly acid surface character (pH(PZC approximately equal) congruent with
      3-4) with very high surface oxygen concentrations (O approximately equal with
      20%). X-ray photoelectron spectroscopy (XPS) analyses of the samples showed the
      oxidation state of the metals was +2 for Co and Mn and +4 for Ti. The presence of
      Mn(II)-doped carbon aerogel enhanced ozone transformation into (*)OH radicals,
      whereas the presence of Co(II) and Ti(IV) carbon aerogels presented no activity
      in this process. Moreover, it was observed that an increase in the concentration
      of Mn in the surface of the aerogel increases its efficiency to transform ozone
      into (*)OH radicals, with an Rct value ([OH]/[O(3)]) of 5.36 x 10(-8) for the
      aerogel doped with 16% of surface Mn(II) compared to an R(ct) of 2.68 x 10(-9)
      for conventional ozonation. Regardless of the aerogel used, XPS analysis of the
      ozonated aerogel samples showed an increase in the concentration of surface
      oxygen when the exposure to ozone was longer. However, presence of oxidized metal
      species after ozone treatment was only detected in the case of the Mn-doped
      aerogel, (Mn(III) and Mn(IV)). CO(2) activation of carbon aerogel produced a
      marked increase in its efficiency to transform ozone into (*)OH radicals compared
      with non-activated sample. The efficiency of Mn activated carbon aerogel to
      transform ozone into (*)OH radicals was greater than that of Witco commercial
      activated carbon or H(2)O(2) in the ozonation of water from Lake Zurich (Zurich,
      Switzerland).

PMID- 16970973
TI  - Impact of H2O2 and (bi)carbonate alkalinity on ammonia's inhibition of bromate
      formation.
AB  - Ammonia can be used to minimize bromate concentrations by blocking two of three
      potential bromate formation pathways. It was theorized that (bi)carbonate
      alkalinity in the presence of ammonia would inhibit bromate formation since the
      pathway that ammonia does not block requires hydroxyl radicals (OH()), and
      (bi)carbonate alkalinity is an OH() scavenger. Experiments where (bi)carbonate
      alkalinity was increased from 50 to 119 mg/L (as CaCO(3)) in the presence of
      excess ammonia resulted in up to 50% reduction in bromate formation, providing
      evidence in support of the theory. While OH() is scavenged by (bi)carbonate
      alkalinity, it is promoted by hydrogen peroxide (H(2)O(2)). When ozone reacts
      with natural organic matter the H(2)O(2) that is formed may therefore render
      ammonia less effective. Experiments conducted in this study demonstrated this
      principle.

PMID- 16970974
TI  - Ag-doped carbon aerogels for removing halide ions in water treatment.
AB  - The objective of this study was to analyze the efficiency of silver(Ag)-doped
      carbon aerogels for the removal of bromide (Br(-)) and iodide (I(-)) from
      drinking waters. Textural characterization of Ag-doped aerogels showed that an
      increase in the Ag dose added during the preparation process produced: (i) a
      reduction in the surface area (S(BET)) and (ii) an increase in mesopore (V(2))
      and macropore (V(3)) volumes. Chemical characterization of the materials revealed
      an acidic surface (pH of point of zero charge, pH(PZC)=4.5, O(surface)=20%). The
      oxidation state of Ag was +1 and the surface concentration of this element ranged
      from 4% to 10%. The adsorption capacity (X(m)) and affinity of adsorbent (BX(m))
      increased with a reduction in the radius of the halogenide. Furthermore, an
      increase in the adsorption capacity was observed with higher Ag concentrations on
      the aerogel surface. The high adsorption capacity of the aerogel may be due to
      the presence of Ag(I) on its surface, with the formation of the corresponding Ag
      halides. Our observations indicate that the halogenides adsorption on commercial
      activated carbon (Sorbo-Norit) is much lower than that of the Ag-doped carbon
      aerogels. The presence of chloride and natural organic matter (NOM) in the medium
      reduced the adsorption capacity of Br(-) and I(-) on Ag carbon aerogels.

PMID- 16970975
TI  - Non-enzymatic interactions of glyoxylate with lysine, arginine, and glucosamine:
      a study of advanced non-enzymatic glycation like compounds.
AB  - Glyoxylate is a 2 carbon aldo acid that is formed in hepatic tissue from
      glycolate. Once formed, the molecule can be converted to glycine by alanine
      glyoxylate aminotransferase (AGAT). In defects of AGAT, glyoxylate is transformed
      to oxalate, resulting in high levels of oxalate in the body. The objective of
      this study was 2-fold. First, it was to determine, if akin to D-glucose, D
      fructose or DL-glyceraldehyde, glyoxylate was susceptible to non-enzymatic attack
      by amino containing molecules such as lysine, arginine or glucosamine. Second, if
      by virtue of its molecular structure and size, glyoxylate was as reactive a
      reagent in non-enzymatic reactions as DL-glyceraldehyde; i.e., a glycose that we
      previously demonstrated to be a more effective glycating agent than D-glucose or
      D-fructose. Using capillary electrophoresis (CE), high performance liquid
      chromatography and UV and fluorescence spectroscopy, glyoxylate was found to be a
      highly reactive precursor of advanced glycation like end products (AGLEs) and a
      more effective promoter of non-enzymatic end products than D-glucose, D-fructose
      or DL-glyceraldehyde.

PMID- 16970976
TI  - Heavy metal concentrations in the general population of Andalusia, South of
      Spain: a comparison with the population within the area of influence of
      Aznalcollar mine spill (SW Spain).
AB  - Levels of metalloids (As - urine) and heavy metals (Hg - urine, Cd - whole blood
      and Zn - serum) were determined by atomic absorption spectrometry in 601 subjects
      living in the area affected by the Aznalcollar mine spill (SW, Spain) and
      compared with those of a representative sample (960 subjects) selected from the
      Andalusian community (non-affected area), southern Spain. The characteristic
      parameters of the analytical method including uncertainty were determined for
      each metal. Potential associations of metal concentration with age, sex and body
      mass index as well as life-style habits (smoking, alcohol consumption and food
      habits) were explored. Concentrations of all the metals studied were
      statistically higher in the population of the affected area with respect to that
      of the non-affected area in Andalusia, although levels were always lower or
      similar to the values reported for the general population and below occupational
      reference limits. In conclusion, there is a lack of evidence that the spill had
      any incidence on human health in the population living in the affected area.
      There are few references in scientific literature reporting values from large
      series of samples, and hence our data could be useful for further studies.

PMID- 16970977
TI  - Accumulation of cadmium in livers and kidneys in Greenlanders.
AB  - In the Arctic, the traditional diet exposes its people to a very high intake of
      cadmium because it is highly concentrated in the liver and kidneys of commonly
      eaten marine mammals. In one study in Greenland, the cadmium intake was estimated
      to 182 microg/day/person in the fall and 346 in the spring. To determine whether
      the cadmium is accumulated in humans, we analyzed autopsy samples of liver and
      kidneys from 95 ethnic Greenlanders (aged 19-89) who died from a wide range of
      causes. The cadmium concentration in liver (overall mean 1.97 microg/g wet wt)
      appeared to be unrelated to any particular age group, whereas the concentrations
      in the kidneys peaked in Greenlanders between 40 and 50 years of age (peak
      concentration 22.3 microg/g wet wt). Despite the high cadmium levels in the
      typical Greenlander diet, we found that the cadmium concentrations in livers and
      kidneys were comparable to those reported from Denmark, Sweden, Australia and
      Great Britain. Furthermore, even though the mean cadmium intake from the diet was
      estimated to be 13-25 times higher in Greenlanders than in Danes, we found
      similar cadmium levels in the kidneys of both. Seal livers and kidneys are the
      main source of cadmium in the diet of Greenlanders, but these tissues are not
      eaten in Denmark. Thus, our results suggest that the accumulation of cadmium from
      Greenlander's marine diet is very low.

PMID- 16970978
TI  - Tumor necrosis factor-alpha in inflammatory myopathies: pathophysiology and
      therapeutic implications.
AB  - OBJECTIVES: To present, in an organized fashion, data from the medical literature
      on the possible role of tumor necrosis factor (TNF)-alpha in the pathogenesis of
      dermatomyositis (DM) and polymyositis (PM), as well as recent clinical studies
      where TNF-inhibition was used as a treatment for myositis. METHODS: PUBMED was
      searched from 1966 to the present using the terms: TNF-alpha, TNF-inhibitors,
      dermatomyositis, polymyositis, myositis, and inflammatory myopathy. In addition,
      relevant abstracts from major recent rheumatology meetings were retrieved.
      RESULTS: Several studies that employed immunostaining and polymerase chain
      reaction analysis in muscle biopsy specimens from patients with inflammatory
      myopathies showed increased presence of TNF-alpha and its soluble receptors in
      inflamed muscle. One genetic study proposed an association between DM and the 
      308A TNF polymorphism. Abnormally high levels of TNF-alpha in the muscle may be
      directly toxic to myofibers, while preventing muscle regeneration. Furthermore,
      TNF-alpha may induce, or augment, the production of other pro-inflammatory
      cytokines such as interleukin (IL)-1, monocyte chemotactic protein-1, IL-6, and
      IL-8. These findings have prompted some investigators to use off-label, TNF
      inhibitors in DM/PM patients, especially if they had failed corticosteroids,
      immune gamma-globulin, and traditional immunosuppressive agents. The results from
      these early, uncontrolled, studies have been promising. CONCLUSION: TNF-alpha may
      have a role in the pathogenesis of the myositis and has emerged as a possible
      therapeutic target. Larger, carefully controlled studies are needed to confirm
      the results from early studies and clearly define the efficacy and safety of anti
      TNF agents in the treatment of inflammatory myopathies.

PMID- 16970979
TI  - Granulomatous hepatitis and Sjogren's syndrome: an association.
AB  - BACKGROUND: Sjogren's syndrome (SS) is a common autoimmune disorder in which
      liver involvement is frequent, but generally mild and subclinical. Multiple
      hepatic histologies have been reported, but to our knowledge an association with
      granulomatous hepatitis (GH) has never been described. We recently evaluated an
      individual in whom biopsy-proven GH was associated with concomitant SS.
      OBJECTIVE: To clarify the possible association between GH and SS. METHODS: We
      retrospectively reviewed all cases of biopsy-proven GH seen in our institution
      from 1991 to 2004. Overall, there were 16 individuals with GH identified of which
      4 were considered idiopathic in origin. These individuals underwent an extensive
      evaluation for the presence of SS as well as other disorders known to be
      associated with GH. RESULTS: Of the 4 identified cases with a previously
      suspected idiopathic GH, 3 met criteria for primary SS. All 3 individuals
      underwent minor salivary gland biopsy, which was diagnostic for this condition.
      CONCLUSIONS: These results suggest a likely association between these 2
      conditions. Further epidemiological studies will be necessary to confirm this
      finding.

PMID- 16970980
TI  - Study of immobilized and extracellular saccharase of watermelon.
AB  - A simple, rapid and reproducible procedure for the identification and
      determination of extracellular saccharase from culture medium of watermelon cell
      suspension cultures is described. The culture medium (without cells) was used for
      the identification and determination of extracellular enzyme activity.
      Intracellular activity was estimated from the cell suspension. Watermelon cell
      suspension was permeabilized by Tween 80 and immobilized by glutaraldehyde. The
      highest saccharase activity was at pH 4.6 at a temperature of 50 degrees C. The
      hydrolysis of substrate was linear 5h after reaching 60% conversion. The cells
      had high saccharase activity and good stability, and in long-term storage they
      showed convenient physico-mechanical properties.

PMID- 16970981
TI  - Effects of shear stress on endothelial cells: possible relevance for ultrasound
      applications.
AB  - This review forms part of a series of papers resulting from a workshop on safety
      of ultrasound applications. The physical effects of ultrasound include generation
      of steady streaming in large fluid volumes, and micro-streaming around contrast
      bubbles. Such streaming induces shear stress acting on the vascular endothelium.
      This review provides a discussion on the levels of endothelial shear stress
      associated with diagnostic ultrasound applications, and on the biological effects
      of shear stress acting on the endothelial cells. Depending on vessel size and
      ultrasound characteristics, shear stresses associated with streaming and micro
      streaming may exceed the physiological levels associated with the flow of blood
      by many orders of magnitude. The resulting biological effects could range
      anywhere from activation of normal shear stress sensors such as ion channels,
      damage of the endothelial surface layer, reversible perforation of the membrane,
      to cell detachment and lysis. The possible presence of such biological effects
      does not necessarily mean that the effects are harmful for the individual.
      However, considering the ever-increasing use of ultrasound, a further
      investigation into these shear stress-related effects, using both experiments and
      modelling, is desired. Apart from safety concerns, such effects may provide a
      base for strategies aimed at targeted delivery of drugs.

PMID- 16970982
TI  - HPV prevalence, E6 sequence variation and physical state of HPV16 isolates from
      patients with cervical cancer in Sichuan, China.
AB  - OBJECTIVES: Infection with high-risk human papillomavirus (hr-HPV) is an
      important factor associated with cervical cancer. The genetic mutation of HPV16
      E6 and integration of HPV16 DNA in the cervical carcinoma tissues are considered
      important genetic changes in cervical lesion progression. But the studies of hr
      HPV epidemiology are relatively less in the area of Sichuan, China. Therefore, we
      investigated the prevalence of 9 high-risk subtypes and analyzed the genetic
      mutation characteristic of HPV16 E6 and physical state of HPV16 DNA. METHODS: The
      fragments of L1 and E6 genes were amplified by PCR or nested PCR and then
      directly sequenced. Further, the multiplex PCR for HPV16 E2 and E6 genes was
      performed for detection of integration. RESULTS: HPV16, 58 and 18 were prominent,
      accounting for 78.6%, 20.0% and 9.7%, respectively in 145 isolates. E6 variants
      revealed that the European (EP) prototype and East Asia (EA) strain were 26
      (23.0%) and 34 (30.1%), respectively. Furthermore, there were 14 base
      substitutions in E6 regions of the study group, of which 12 resulted in amino
      acid changes and the rest was silent mutation. Significantly, the 240G
      substitution exactly located the P53 degradation site. Overall, 8 of 114 (7.0%)
      isolates only contained integrated HPV16 DNA, 43 (37.7%) only contained episomal
      DNA and 63 (55.3%) contained both integrated and episomal DNA. The proportion of
      disruption of an intact E2 gene in the patients with cervical cancer is much
      lower than that in the previous studies. CONCLUSIONS: HPV16, 58 and 18 were
      mainly prevailing subtypes in patients with cervical cancer from Sichuan areas,
      China and EP/EA strains were predominant in these areas. Some mutations of E6
      gene, which lead to the amino acid changes, may be more potentially carcinogenic
      and the proportion of disruption of an intact E2 gene is much lower.

PMID- 16970983
TI  - The differential influences of melanocortins on nociception in the formalin and
      tail flick tests.
AB  - Melanocortins exert multiple physiological effects that include the modulation of
      immune responses, inflammation processes, and pain transmission. In the present
      study we investigated the peripheral activity of natural melanocortins - alpha-,
      beta-, gamma1- and gamma2-melanocyte stimulating hormone (MSH) - and melanocortin
      receptor subtypes 3 and 4 (MC3/4 receptor) antagonist HS014 in pain (formalin and
      tail flick) tests after peptide subcutaneous administration in mice. In the
      formalin test, among all substances tested only alpha-MSH (1 micromol/kg)
      statistically significantly inhibited the formalin-induced first phase pain
      response, however, all tested peptides (except gamma1-MSH) at the dose of 1
      micromol/kg produced a pronounced inhibitory effect on nociceptive behavior in
      the second phase and this activity was comparable with that of indomethacin
      (reference drug, 5 mg/kg intraperitoneally); beta-MSH was also active at a dose
      0.1 micromol/kg. In the tail flick test, alpha-MSH (1 micromol/kg) showed
      algesic, whereas HS014 (0.5 micromol/kg) and indomethacin (10 mg/kg) exerted
      analgesic activity. Other peptides did not exert any activity in the tail flick
      test. These data indicate that peripherally administered melanocortin receptor
      agonists alpha-MSH, beta-MSH and gamma2-MSH, as well as MC3/4 receptor antagonist
      HS014 induced antinociception on pain/inflammatory events caused by formalin
      suggesting a predominant anti-inflammatory role of these peptides.

PMID- 16970984
TI  - Effects of estradiol valerate on voluntary alcohol consumption, beta-endorphin
      content and neuronal population in hypothalamic arcuate nucleus.
AB  - The main goal of the present experiment was to study the voluntary consumption of
      alcohol before and after a single injection of estradiol valerate (EV); another
      goal was to assess beta-endorphin (beta-EP) neurons and beta-EP peptide in
      hypothalamic arcuate nucleus 10 weeks after the injection of EV. Wistar female
      rats were injected either with a single 2.0 mg/rat injection of EV or with 0.2 ml
      of corn oil/rat (vehicle group). Two weeks before the injection and 10 weeks
      after it, every other day both groups were exposed to a free-choice alcohol
      drinking procedure. In weeks 4 and 5, the post-injection-consumption of alcohol
      was higher in the EV group than the vehicle group. In the EV group, food intake
      decreased and coincided with body weight lost in week 1 of post-EV injection. EV
      treated females showed significantly lower number of beta-EP neurons than control
      group (reduction of 51.22%); however, beta-EP content was similar in both groups,
      and they did not differ in the number of TSH and LHRH neurons. The present
      results suggest a positive relationship between high alcohol consumption and
      possible initial deficiency of beta-endorphin content. The transient increase in
      alcohol consumption suggests a possible compensatory secretory effect of the
      surviving beta-endorphinergic neurons, particularly when they are chronically
      stimulated with alcohol.

PMID- 16970986
TI  - Adsorption of papain with Cibacron Blue F3GA carrying chitosan-coated nylon
      affinity membranes.
AB  - Covalent coupling of chitosan (CS) to activated nylon membrane was performed
      after the reaction of the microporous nylon membrane with formaldehyde. Non
      specific adsorption on the CS-coated nylon membrane decreased greatly, compared
      with plain nylon membrane. The dye Cibacron Blue F3GA (CB F3GA) as a ligand was
      then covalently immobilized on the CS-coated membranes. Physical properties of
      the composite membrane and its applications in affinity membrane chromatography
      were examined. The contents of CS and CB F3GA-attached membranes were 89.6 mg/g
      nylon membrane and 146.1 micromol/g nylon membrane, respectively. These CB F3GA
      attached composite membranes were used in the papain adsorption studies. Higher
      papain adsorption capacity, up to 235.3mg/g affinity membrane, was obtained. The
      adsorption isotherm fitted the Freundlich model well. Significant amount of the
      adsorbed papain (about 94.3%) was eluted by 1.0M NaSCN at pH 9.0. Experiments on
      regeneration and dynamic adsorption were also performed. It appears that CB F3GA
      CS nylon membranes can be applied for papain separation without causing any
      denaturation.

PMID- 16970985
TI  - Brain responses to filled gaps.
AB  - An unresolved issue in the study of sentence comprehension is whether the process
      of gap-filling is mediated by the construction of empty categories (traces), or
      whether the parser relates fillers directly to the associated verb's argument
      structure. We conducted an event-related potentials (ERP) study that used the
      violation paradigm to examine the time course and spatial distribution of brain
      responses to ungrammatically filled gaps. The results indicate that the earliest
      brain response to the violation is an early left anterior negativity (eLAN). This
      ERP indexes an early phase of pure syntactic structure building, temporally
      preceding ERPs that reflect semantic integration and argument structure
      satisfaction. The finding is interpreted as evidence that gap-filling is mediated
      by structurally predicted empty categories, rather than directly by argument
      structure operations.

PMID- 16970987
TI  - Progressive disease in chronic lymphocytic leukemia is correlated with the DNA
      methylation index.
AB  - The DNA methylation index (MI) is calculated as a percentage of methylated
      cytosines to cytosines. We established the DNA MI in 100 normal individuals
      ranging in age between 1 month and 94 years and found that the age-specific DNA
      MI can be calculated (4.00-0.0034 x age). We determined the DNA MI in 23 patients
      with CLL ranging from 47 to 90 years and compared the results with age-matched
      controls. Using Cox proportional hazard models for MI, adjusting for age and
      white blood cell count, only the DNA MI correlated with early clinical
      indications for systemic therapy (p=0.0038, HR=7.00, 95% CI: 1.90-26.20).

PMID- 16970988
TI  - Maternal smoking behavior, background and neonatal health in Finnish children
      subsequently placed in foster care.
AB  - OBJECTIVE: The purpose of this study was to investigate retrospectively neonatal
      health and maternal background among a sample of children taken into custody and
      placed in foster care and to investigate the relation between medical and social
      risk in the neonatal period. METHOD: The data-linkage study combined two
      registries: the Finnish Medical Birth Registry (MBR), from January 1, 1987 to
      December 31, 1989, and the Finnish Child Welfare Registry (CWR) from January 1,
      1987 to December 31, 1997 using personal identification numbers (n=1,668). As
      controls all Finnish children born in 1987 were chosen (n=59,727). Infant
      neonatal health was estimated using the following indicators: birth-weight and
      birth-length, birth-weight by gestational age, 1-minute Apgar scores, and
      discharge age from the nursery. Maternal background characteristics included
      maternal age, parity, marital status, number of antenatal visits at maternity
      clinics and smoking during pregnancy. RESULTS: We found that the 1,668 children
      in the study had a lower birth-weight and birth-length, shorter gestational age,
      lower 1-minute Apgar scores and later discharge from the nursery than the
      population-based controls. The proportion of teen-age mothers was about four
      times higher and the proportion of unmarried women was twice as high. A majority
      of the women (56%) reported smoking during pregnancy, compared with only 15% of
      the population-based comparisons. Children subsequently taken into custody had
      poorer health at the time of birth than other children and these differences
      could only partly be explained by the differences in smoking habits during
      pregnancy. The women in the study made use of the free health controls at
      maternity clinics as much as the population-based comparisons. CONCLUSIONS: Our
      findings indicate that social and medical risks are related in the neonatal
      period. Since almost all mothers visit maternity clinics, there are possibilities
      for early intervention.

PMID- 16970989
TI  - Update on viral accommodation, a model for host-viral interaction in shrimp and
      other arthropods.
AB  - Comparatively little published information is available on the mechanistic
      response of shrimp and other arthropods to viral pathogens. Much of the
      literature has been focused on the use of viruses for biological control of
      insect pests or disease vectors and on the use of baculoviruses as a means of
      heterologous protein expression in insect cell lines. The situation changed
      dramatically with the rapid global increase in cultivation of penaeid shrimp and
      the massive farm losses that have occurred due to viral pathogens. Urgency to
      solve these problems has led to a closer examination of the shrimp response to
      viral pathogens in the hope of finding new methods of disease control. Field
      observations and results of laboratory experiments in the past decade indicate
      that shrimp may be capable of a specific, adaptive response to viral pathogens
      that cannot be explained by current knowledge and understanding of their cellular
      and humoral defenses. Hallmarks of this response are specific tolerance to single
      and multiple viral infections without gross or histological signs of disease, a
      phenomenon common to crustaceans and insects. The concept of viral accommodation
      was introduced in 1998 as a simple testable hypothesis to explain these
      phenomena. Key elements of the hypothesis were an unknown mechanism for specific
      memory of pathogens and the role of this memory in dampening viral triggered
      apoptosis. Recent field and research results have supported predictions of the
      viral accommodation hypothesis and suggest that memory may be provided by the
      viral pathogens themselves in persistent infections that result in reduced
      severity of disease. The well-known phenomenon of defective interfering viral
      particles may play an important role in this process, but it cannot explain cross
      protection that has recently been described for heterologous viral infections.
      The major conclusion is that homologous and heterologous reduction in disease
      severity resulting from persistent viral infections (i.e., accommodated viral
      infections) may be a key process that has evolved from host viral interaction in
      the arthropod line.

PMID- 16970990
TI  - Identification of putative DnaN-binding motifs in plasmid replication initiation
      proteins.
AB  - Recently the plasmid RK2 replication initiation protein, TrfA, has been shown to
      bind to the beta subunit of DNA Polymerase III (DnaN) via a short pentapeptide
      with the consensus QL[S/D]LF. A second consensus peptide, the hexapeptide QLxLxL,
      has also been demonstrated to mediate binding to DnaN. Here we describe the
      results of a comprehensive survey of replication initiation proteins encoded by
      bacterial plasmids to identify putative DnaN-binding sites. Both pentapeptide and
      hexapeptide motifs have been identified in a number of families of replication
      initiation proteins. The distribution of sites is sporadic and closely related
      families of proteins may differ in the presence, location, or type of putative
      DnaN-binding motif. Neither motif has been identified in replication initiation
      proteins encoded by plasmids that replicate via rolling circles or strand
      displacement. The results suggest that the recruitment of DnaN to the origin of
      replication of a replisome by plasmid replication initiation proteins is not
      generally required for plasmid replication, but that in some cases it may be
      beneficial for efficiency of replication initiation.

PMID- 16970991
TI  - Glycerolipid transfer for the building of membranes in plant cells.
AB  - Membranes of plant organelles have specific glycerolipid compositions. Selective
      distribution of lipids at the levels of subcellular organelles, membrane leaflets
      and membrane domains reflects a complex and finely tuned lipid homeostasis.
      Glycerolipid neosynthesis occurs mainly in plastid envelope and endoplasmic
      reticulum membranes. Since most lipids are not only present in the membranes
      where they are synthesized, one cannot explain membrane specific lipid
      distribution by metabolic processes confined in each membrane compartment. In
      this review, we present our current understanding of glycerolipid trafficking in
      plant cells. We examine the potential mechanisms involved in lipid transport
      inside bilayers and from one membrane to another. We survey lipid transfers going
      through vesicular membrane flow and those dependent on lipid transfer proteins at
      membrane contact sites. By introducing recently described membrane lipid
      reorganization during phosphate deprivation and recent developments issued from
      mutant analyses, we detail the specific lipid transfers towards or outwards the
      chloroplast envelope.

PMID- 16970992
TI  - A neural network model for combining clinical predictors of antidepressant
      response in mood disorders.
AB  - Artificial neural networks (ANN) represent a promising tool for combining
      multiple predictors in complex diseases. Antidepressant response in mood
      disorders is a typical complex phenomenon were a number of predictors influence
      outcome under non-linear interactions. In the present study we tested a neural
      network strategy for antidepressant outcome in subjects affected by major
      depression. One hundred and forty-five never reported depressed inpatients were
      included in this study (major depressives/bipolars: 111/34). A multi layer
      perceptron network composed of 1 hidden layer with 13 nodes was chosen. The
      network was performed on the sample of 145 cases divided as follows: train
      73+verify 36+test 36. Correlation of predicted versus observed response was 0.46
      in the test (independent) sample that corresponds to 21% of variance explained.
      Number of episodes, side effects, delusional features, baseline HAM-D, length of
      current episode, lithium augmentation, current medical condition and personality
      disorders were the main factors identified by the model. Sex, age at onset,
      polarity, plasma level and baseline VAS score were part of the model but with a
      lower rank. Overall, our findings suggest that neural networks could be a valid
      technique for the analysis of psychopharmacology studies. The complex
      interactions modelled through ANN may be eventually applied at the clinical level
      for the individualized therapy.

PMID- 16970993
TI  - Atypical antipsychotics related metabolic syndrome in bipolar patients.
AB  - BACKGROUND: This is the first study in bipolar patients, aimed to evaluate
      possible roles of the drugs, [atypical antipsychotics (AA) and mood stabilizers
      (MS)], inducing metabolic syndrome (MetS). METHODS: 125 bipolar patients,
      diagnosed according to the DSM IV, were assessed cross-sectionally for MetS
      according to the National Cholesterol Educational Program criteria (NCEP ATP
      III). Patients included in the study were required to receive medications (AAs:
      quetiapine, risperidone and olanzapine, and MSs: Lithium, Sodium Valproate,
      Carbamazepine, Lamotrigine) for at least 3 months. Patients are divided into
      three groups as only AA users, AA+MS users and only MS users. RESULTS: Of the
      patients, 32% were MetS, a proportion higher than normal population and similar
      as previous studies in bipolar patients. AA taking patients had significantly
      higher MetS rates than the others (chi(2)=10.47 df=2 p=0.005). Also, AA taking
      patients had significantly higher MetS rates than MS taking patients (chi(2)=8.86
      df=1 p=0.003). There was no significant difference among quetiapine, olanzapine,
      risperidone usage for MetS prevalences (chi(2)=0.38 df=2 p=0.82). CONCLUSIONS: AA
      taking bipolar patients had higher MetS rates. Despite already existing data on
      MetS and antipsychotics, this cross-sectional study is the first research,
      discusses AAs and MSs for inducing MetS in bipolar disorder. Prospectively
      designed researches should be conducted for further clarification of the role of
      these drugs in MetS.

PMID- 16970995
TI  - Resistance of herpes simplex virus type 1 to acyclovir: thymidine kinase gene
      mutagenesis study.
AB  - By site-directed mutagenesis, we investigate the role of six mutations of herpes
      simplex virus type 1 thymidine kinase (TK) gene in the acquisition of resistance
      to acyclovir (ACV). TK activity was not impaired by substitutions located at
      codons 17, 161 and 374 and these mutations were thus related to TK gene
      polymorphism. Mutations His105Pro, Leu364Pro and Asp162Ala lead to the loss of TK
      activity that could result in ACV-resistance.

PMID- 16970996
TI  - NMDA antagonist MK-801 impairs acquisition of place strategies, but not their
      use.
AB  - Evidence that NMDA receptors contribute to synaptic plasticity in the hippocampus
      has stimulated research on their role in behavioral learning and memory. Recent
      studies indicate that NMDA antagonists decrease use of place strategies by rats
      in a T-maze task that can be solved using either a "place" or "response"
      strategy. In the present study, rats were given MK-801 before maze exposure
      and/or training on this redundant strategy T-maze task. MK-801 did not impair
      rats' ability to learn the task, but did change the strategies they used on a
      probe trial administered after learning. MK-801 decreased use of place strategies
      only when administered before both maze exposure and training; rats given MK-801
      only before maze exposure or only before training tended to use place strategies
      on the probe trial. These results show that MK-801 does not prevent rats from
      utilizing previously acquired spatial information, but does appear to impair the
      acquisition of spatial information needed for place strategies.

PMID- 16970997
TI  - Therapeutic and protective effect of environmental enrichment against psychogenic
      and neurogenic stress.
AB  - Environmental enrichment (EE) has beneficial neurobiological, physiological and
      behavioral effects. The purpose of the present paper is to review the animal
      research literature pertaining to the impact of EE on altering physiological and
      behavioral anxiety outcomes. Evidence supports the view that EE attenuates
      responses to certain anxiety provoking situations, and that these effects persist
      over time. Specifically, EE attenuates behavioral anxiety-type responses and
      endocrine responses mediated via the hypothalamic-pituitary-adrenal (HPA) axis
      evoked by psychogenic and/or neurogenic stressors. EE is not only able to protect
      from excessive anxiety in response to a present stressor, but also attenuates the
      enduring or persistent effects engendered by past psychogenic stressor(s) such as
      prenatal stress or neonatal maternal separation. It is noteworthy that the
      protective effects of EE are particularly apparent in animals that are highly
      anxious or when the task is highly challenging for the subject. Various
      mechanisms of action of EE have been proposed, ranging from behavioral/cognitive
      to cellular/molecular processes. A pronounced variability in the enrichment
      protocols used by different investigators may account for some of the
      inconsistencies noted in the effect of EE on behavioral (e.g. anxiety) and
      endocrine (e.g. plasma corticosterone) responses. Although the occasional
      inconsistencies highlight the need for further research, a preponderance of the
      animal research data indicates that EE exerts therapeutic and protective
      (anxiolytic) effects against (a) impending threat, (b) enduring effects of past
      stressor(s) and (c) subsequent stressors.

PMID- 16970998
TI  - Gender specific effects of ethanol in mice, lacking CCK2 receptors.
AB  - Neuropeptide cholecystokinin (CCK) has been reported to suppress ethanol intake,
      but there is contradictory evidence about the role of CCK(2) receptors. In the
      present study anxiolytic, hypolocomotor and sedative effects of acute ethanol
      administration, but also voluntary ethanol consumption were studied in male and
      female mice, lacking CCK(2) receptors (-/-). Ethanol (1.0 and 2.0 g/kg) induced a
      significant reduction of anxiety-related behaviours in the elevated plus-maze,
      but this effect was statistically significant only in female homozygous mice (-/
      ). In male mice, lacking CCK(2) receptors (-/-), but not in their wild-type
      littermates (+/+), the suppression of vertical locomotor activity was caused by
      ethanol at a dose 0.5 g/kg. The highest dose of ethanol (2.0 g/kg) produced
      statistically significant reduction of horizontal locomotor activity only in
      female wild-type (+/+) mice, but this effect was related to increased basal
      activity when compared to female mutant (-/-) mice. Duration of the loss of
      righting reflex was not significantly affected by genotype or gender, but blood
      ethanol levels at regain of righting reflex were significantly lower in female
      homozygous mice (-/-) compared to their wild-type (+/+) littermates, indicating
      increased sensitivity to the sedative effect of ethanol. Ethanol intake, but not
      preference, at concentration 10% was significantly increased in female mice,
      lacking CCK(2) receptors (-/-). The present study revealed an altered response to
      the acute effects of ethanol in CCK(2) receptor deficient mice (-/-). These
      changes are gender-specific and could be attributed to the altered activity of
      dopaminergic system in male mice and increased activity of GABA-ergic system in
      female mice as established in our previous studies.

PMID- 16970999
TI  - Visual field recovery after vision restoration therapy (VRT) is independent of
      eye movements: an eye tracker study.
AB  - AIM: It has been argued that patients with visual field defects compensate for
      their deficit by making more frequent eye movements toward the hemianopic field
      and that visual field enlargements found after vision restoration therapy (VRT)
      may be an artefact of such eye movements. In order to determine if this was
      correct, we recorded eye movements in hemianopic subjects before and after VRT.
      METHODS: Visual fields were measured in subjects with homonymous visual field
      defects (n=15) caused by trauma, cerebral ischemia or haemorrhage (lesion age >6
      months). Visual field charts were plotted using both high-resolution perimetry
      (HRP) and conventional perimetry before and after a 3-month period of VRT, with
      eye movements being recorded with a 2D-eye tracker. This permitted quantification
      of eye positions and measurements of deviation from fixation. RESULTS: VRT lead
      to significant visual field enlargements as indicated by an increase of stimulus
      detection of 3.8% when tested using HRP and about 2.2% (OD) and 3.5% (OS) fewer
      misses with conventional perimetry. Eye movements were expressed as the standard
      deviations (S.D.) of the eye position recordings from fixation. Before VRT, the
      S.D. was +/-0.82 degrees horizontally and +/-1.16 degrees vertically; after VRT,
      it was +/-0.68 degrees and +/-1.39 degrees , respectively. A cluster analysis of
      the horizontal eye movements before VRT showed three types of subjects with (i)
      small (n=7), (ii) medium (n=7) or (iii) large fixation instability (n=1).
      Saccades were directed equally to the right or the left side; i.e., with no
      preference toward the blind hemifield. After VRT, many subjects showed a smaller
      variability of horizontal eye movements. Before VRT, 81.6% of the recorded eye
      positions were found within a range of 1 degrees horizontally from fixation,
      whereas after VRT, 88.3% were within that range. In the 2 degrees range, we found
      94.8% before and 98.9% after VRT. Subjects moved their eyes 5 degrees or more
      0.3% of the time before VRT versus 0.1% after VRT. Thus, in this study, subjects
      with homonymous visual field defects who were attempting to fixate a central
      target while their fields were being plotted, typically showed brief horizontal
      shifts with no preference toward or away from the blind hemifield. These eye
      movements were usually less than 1 degrees from fixation. Large saccades toward
      the blind field after VRT were very rare. CONCLUSION: VRT has no effect on either
      the direction or the amplitude of horizontal eye movements during visual field
      testing. These results argue against the theory that the visual field
      enlargements are artefacts induced by eye movements.

PMID- 16971000
TI  - Inhibition within the nucleus tractus solitarius (NTS) ameliorates environmental
      exploration deficits due to cerebellum lesions in an animal model for autism.
AB  - Clinical observations suggest that abnormalities within the cerebellum and/or the
      cerebellum--cholinergic forebrain connections may be key to explain the severe
      behavioral deficits and increases in seizures seen in autism. In order to explore
      functional relationships between brain areas implicated in many of the core
      behavioral features of autism, experiments utilizing animal models for specific
      autism-like behaviors have increased in recent years. In the current study, we
      used a rodent model for the autism-like behavior of environment exploration
      deficits to examine the role of the cerebellum and its connectivity to the
      forebrain. In addition, due to the possible common neural pathways between
      seizures and autism-like behaviors, we explored the possibility for limiting
      autism-like behaviors via antiseizure brainstem and cerebellar circuitry. In two
      experiments, adult male rats showed a significant decrease in exploration
      behavior following developmental cerebellar suction lesions (experiment 1) or
      i.c.v. saporin injections specifically targeting Purkinje cells, but not after
      the addition of saporin-induced cholinergic forebrain lesions (experiment 2). In
      both experiments, the anticonvulsant treatment of inhibition of the medullary
      nucleus tractus solitarius (NTS) restored exploration behavior to control levels.
      These findings suggest that specific neuronal populations within the cerebellum
      are responsible for mediating exploration behavior, and these neuronal
      populations are similar to the circuitry involved in limbic motor seizures in
      that they are sensitive to brainstem inhibition. Furthermore, these results
      suggest this connection could be utilized in order to control behavioral deficits
      seen in autism with treatments, such as vagal nerve stimulation, which are
      effective against pharmaco-resistant seizures.

PMID- 16971001
TI  - Colony formation of C57BL/6J mice in visible burrow system: identification of
      eusocial behaviors in a background strain for genetic animal models of autism.
AB  - Deficits in social interaction are primary characteristics of autism, which has
      strong genetic components. Genetically manipulated mouse models may provide a
      useful research tool to advance the investigation of genes associated with
      autism. To identify these genes using mouse models, behavioral assays for social
      relationships in the background strains must be developed. The present study
      examined colony formation in groups of one male and three female mice (Experiment
      1) and, groups of three male mice (Experiment 2) of the C57BL/6J strain in a semi
      natural visible burrow system. For adult mixed-sex colonies, 4-h observations
      during both the dark and light cycles for 15 days demonstrated day-dependent
      increases in huddling together in the chamber accompanied by decreased
      frequencies of active social behaviors. Sequential analyses of social
      interactions indicated that approaches to the back of the approached animal
      typically elicited flight, while approaches to the front of the approached animal
      failed to do so. This was seen for female to female, and for female to male
      approaches, as well as male to female approaches, strongly counterindicating a
      view that rear approach/flight specifically reflects female responsivirity to
      unwanted male sexual approach. For adult male colonies, similar protocols found
      that these social behaviors were similar to those of adult mixed-sex colonies.
      These findings suggest two potentially useful measures of eusocial behavior in
      mice, of possible value for genetic mouse models of autism; that is, huddling
      together and approaches to the front but not the back, of conspecifics.

PMID- 16971003
TI  - Influence of parenting style on the offspring's behaviour and CSF monoamine
      metabolite levels in crossfostered and noncrossfostered female rhesus macaques.
AB  - We investigated the association between variation in parenting style and the
      offspring's behaviour and CSF monoamine metabolite (5-HIAA, HVA, and MHPG) levels
      in rhesus monkeys. Study subjects were 25 two-year-old females reared by their
      biological mothers and 15 same-aged females that were crossfostered at birth and
      reared by unrelated mothers. Subjects that were rejected more by their mothers in
      the first 6 months of life engaged in more solitary play and had lower CSF
      concentrations of 5-HIAA than subjects that were rejected less. The relation
      between these variables was generally similar in crossfostered and
      noncrossfostered females. CSF levels of 5-HIAA were negatively correlated with
      rates of scratching, a behavioural indicator of anxiety. These results suggest
      that that early exposure to high rates of maternal rejection can result in higher
      anxiety later in life, and that this effect may be mediated by serotonergic
      mechanisms. Variation in maternal protectiveness did not affect offspring
      behaviour and neither protectiveness nor rejection affected CSF levels of HVA and
      MHPG. CSF levels of MHPG, however, were negatively correlated with solitary play
      behaviour and avoidance of other individuals, suggesting that individuals with
      lower CSF MHPG were more fearful and socially phobic than those with higher CSF
      MHPG. Taken together, these findings suggest that individual differences in
      anxiety and fearfulness in young rhesus monkeys are accounted for, at least in
      part, by variation in CSF levels of monoamine metabolites, and that the
      development of brain monoamine systems, particularly serotonin, can be affected
      by early exposure to variable maternal behaviour.

PMID- 16971004
TI  - Angiotensin II and Aldosterone stimulating NF-kappaB and AP-1 activation in
      hepatic fibrosis of rat.
AB  - BACKGROUND/AIMS: Intrahepatic renin-angiotensin-aldosterone system (RAAS) plays a
      key role in the fibrogenesis of liver. However, the signal transduction mechanism
      underlying effects of Angiotensin II (Ang II) and Aldosterone (Aldo) on Nuclear
      Factor-kappaB (NF-kappaB) and active protein-1 (AP-1) pathway in hepatic
      fibrogenesis remains to be fully elucidated. The present study aims to
      investigate the signal transduction mechanism underlying effects of Ang II and
      Aldo on NF-kappaB and AP-1 pathway during hepatic fibrogenesis. METHODS: To
      assess the effect of AECI and Angiotensin II type 1 receptor (AT-1 receptor)
      blocker on NF-kappaB activity in liver, a model of fibrosis was performed in rat.
      In vitro, hepatic stellate cells (HSCs)-T6 cells were preincubated for 1 h or not
      with U0126, a specific inhibitor of extracellular signal regulated kinase (ERK),
      irbesartan, and N-acetylcysteine prior to exposure to Ang II or Aldo for the
      indicated times. DNA binding activity of NF-kappaB and AP-1 were analyzed by
      Electrophoretic mobility shift assay (EMSA). Western blot was used to detect
      expression of IkappaBalpha and Phospho-P42/44. RT-PCR was used to detect the
      expressions of tumor necrosis factor alpha (TNFalpha) mRNA and alpha1 (I)
      procollagen mRNA. RESULTS: AECI and AT-1 receptor blocker exert anti-fibrosis
      effect through inhibiting NF-kappaB activation in liver. Ang II and Aldo increase
      HSCs NF-kappaB activity and NF-kappaB target gene-TNFalpha expression by
      inhibiting IkappaBalpha expression in a redox-sensitive manner. Ang II and Aldo
      also markedly increase HSCs AP-1 activity and AP-1 target gene-alpha1 (I)
      procollagen mRNA expression via ERK1/2 pathway in a redox-sensitive manner.
      CONCLUSIONS: These results show that stimulation of NF-kappaB and AP-1 pathway
      mediate hepatic fibrogenesis induced by intrahepatic RAAS.

PMID- 16971005
TI  - Competition among differentiated health plans under adverse selection.
AB  - Market power and adverse selection are prevalent features of the market for pre
      paid health plans. However, most of the literature on adverse selection considers
      extreme cases: either perfect competition or monopoly. If instead health plans
      are horizontally differentiated, then (i) profits derived from each low risk are
      higher than from each high risk and (ii) when the profits derived from each high
      risk are negative (cross-subsidization), a health authority as informed as the
      health plans can implement a Pareto-improvement. Both local and global deviations
      from cross-subsidization are addressed within a Nash equilibrium framework.

PMID- 16971002
TI  - Mouse behavioral tasks relevant to autism: phenotypes of 10 inbred strains.
AB  - Three defining clinical symptoms of autism are aberrant reciprocal social
      interactions, deficits in social communication, and repetitive behaviors,
      including motor stereotypies and insistence on sameness. We developed a set of
      behavioral tasks designed to model components of these core symptoms in mice.
      Male mice from 10 inbred strains were characterized in assays for sociability,
      preference for social novelty, and reversal of the spatial location of the
      reinforcer in T-maze and Morris water maze tasks. Six strains, C57BL/6J, C57L/J,
      DBA/2J, FVB/NJ, C3H/HeJ, and AKR/J, showed significant levels of sociability,
      while A/J, BALB/cByJ, BTBR T(+)tf/J, and 129S1/SvImJ mice did not. C57BL/6J,
      C57L/J, DBA/2J, FVB/NJ, BALB/cByJ, and BTBR T(+)tf/J showed significant
      preference for social novelty, while C3H/HeJ, AKR/J, A/J, and 129S1/SvImJ did
      not. Normal scores on relevant control measures confirmed general health and
      physical abilities in all strains, ruling out artifactual explanations for social
      deficits. Elevated plus maze scores confirmed high anxiety-like behaviors in A/J,
      BALB/cByJ, and 129S1/SvImJ, which could underlie components of their low social
      approach. Strains that showed high levels of performance on acquisition of a T
      maze task were also able to reach criterion for reversal learning. On the Morris
      water maze task, DBA/2J, AKR/J, BTBR T(+)tf/J, and 129S1/SvImJ failed to show
      significant quadrant preference during the reversal probe trial. These results
      highlight a dissociation between social task performance and reversal learning.
      BTBR T(+)tf/J is a particularly interesting strain, displaying both low social
      approach and resistance to change in routine on the water maze, consistent with
      an autism-like phenotype. Our multitask strategy for modeling symptoms of autism
      will be useful for investigating targeted and random gene mutations, QTLs, and
      microarray analyses.

PMID- 16971006
TI  - Overcoming acetate in Escherichia coli recombinant protein fermentations.
AB  - Escherichia coli is the organism of choice for the expression of a wide variety
      of recombinant proteins for therapeutic, diagnostic and industrial applications.
      E. coli generates acetic acid (acetate) as an undesirable by-product that has
      several negative effects on protein production. Various strategies have been
      developed to limit acetate accumulation or reduce its negative effects to
      increase the productivity of recombinant proteins. This article reviews recent
      strategies for reducing or eliminating acetate, including approaches that
      optimize the protein production process as well as those that involve modifying
      the host organism itself.

PMID- 16971007
TI  - Wastewater treatment: a model system for microbial ecology.
AB  - Biological wastewater treatment is among the most important biotechnological
      applications and, as drivers of the key processes, microorganisms are central to
      its success. Therefore, the study of wastewater microorganisms has obvious
      applied significance; however, the importance of wastewater treatment reactors as
      model systems for microbial ecology is often overlooked. Modern molecular
      techniques, including environmental genomics, have identified unexpected
      microbial key players for nutrient removal and sludge bulking and/or foaming, and
      provided many exciting insights into the diversity, functions and niche
      differentiations of these predominantly uncultivated microorganisms. It is now
      time for wastewater microbiology to be recognized as a mature and dynamic
      discipline in its own right, offering much toward a deeper understanding of life
      in complex microbial communities. Here, we consider selected key findings to
      illustrate the past and future roles of molecular ecophysiology and genomics in
      the development of wastewater microbiology as an important subdiscipline of
      microbial ecology.

PMID- 16971008
TI  - Carbon ion radiation therapy for prostate cancer: results of a prospective phase
      II study.
AB  - BACKGROUND AND PURPOSE: To determine the efficacy and feasibility of carbon ion
      radiotherapy (C-ion RT) for prostate cancer. PATIENTS AND METHODS: Between April
      2000 and November 2003, 175 patients received C-ion RT using a recommended dose
      fractionation (66.0 GyE/20 fractions) established from prior studies. C-ion RT
      alone was performed for 33 patients constituting a low-risk group (Stage < or
      =T2a and PSA <20 ng/ml and Gleason score < or =6); the remaining 142 high-risk
      patients received an additional androgen deprivation therapy (ADT). RESULTS: The
      4-year overall survival and bNED rates were 91% and 87%, respectively. Local
      control was achieved in all but one patient. The 4-year bNED rates were 87% in
      the low-risk group and 88% in the high-risk group. In very advanced diseases
      (Stage > or= T3a or PSA > or= 20 ng/ml or Gleason score > or =8), there was
      significant difference in the bNED rate according to period of ADT administration
      (ADT > or =24 months: 93%, ADT <24 months: 73%, p<0.01). Grade 2 late toxicities
      developed in 4 patients (2%) for the rectum and 9 patients (5%) for the
      genitourinary system but no Grade 3 or higher toxicity was observed. CONCLUSIONS:
      The effectiveness of C-ion RT for prostate cancer has been well confirmed. Based
      on these results, new study of a C-ion RT modified for the administration
      strategy of ADT according to the patient risk has been started by dividing
      patients into 3 groups, high-risk, intermediate-risk, and low-risk.

PMID- 16971009
TI  - Re-irradiation in the management of isolated neck recurrences: current status and
      recommendations.
AB  - Recent times have witnessed significant improvements in outcome for head and neck
      squamous cell carcinomas. Nevertheless, the major pattern of failure continues to
      remain loco-regional. Isolated neck recurrence, although uncommon, occurs in 5-7%
      of patients after radical treatment. The options for this subgroup are somewhat
      limited and are often guided by empiricism rather than evidence. This review
      attempts to systematically analyze the therapeutic options for patients with
      isolated neck recurrence following radical treatment for the primary and draining
      cervical lymph nodes, with a special emphasis on re-irradiation. Salvage neck
      dissection offers the best chance of cure to patients with resectable neck
      recurrences. The perceived increased risk of complications of re-irradiation
      following previous curative dose irradiation has precluded optimal evaluation of
      its potential in this setting. Post-operative adjuvant re-irradiation should be
      based on histo-pathological findings of the salvage surgery. Re-irradiation with
      or without chemotherapy may be considered for unresectable neck recurrences. The
      role of chemotherapy continues to evolve and is presently not optimally defined.
      There is lack of high-quality evidence pertinent to salvage therapy leading to
      vast variations in practice. More patients with recurrent disease should be
      enrolled onto prospective clinical trials with relevant and meaningful endpoints.

PMID- 16971010
TI  - An "in silico" clinical trial comparing free breathing, slow and respiration
      correlated computed tomography in lung cancer patients.
AB  - BACKGROUND AND PURPOSE: To determine which method of internal target volume (ITV)
      definition based on a respiration correlated CT (RCCT) allows optimal tumor
      coverage. MATERIAL AND METHODS: A free breathing CT (CT(fb)) and an RCCT scan
      were acquired in 41 lung cancer patients. For 12 patients with a motion >7 mm in
      any direction, a detailed analysis was made. The RCCT scan was used to measure
      tumor motion and to reconstruct a CT at 10 phases (CT(10ph)), amongst which the
      half ventilation CT (CT(hv)). By averaging the CT(10ph), a slow CT (CT(slow)) was
      reconstructed. Based on those scans ITVs were delineated and treatments were
      planned, where for the ITV(hv) an internal margin of (motion amplitude)/4 was
      used. The treatment plans for the ITVs were projected on the 10 respiration
      phases. Doses were calculated and averaged over the 10 phases to estimate the
      actual CTV coverage. RESULTS: The 3D motion was on average 8.1+/-1.0 mm (1 SD)
      for all patients; no statistical difference was found between lower and upper
      lobe tumors. The ITV(slow) was the smallest volume on average (142+/-38 cm(3)),
      followed by the ITV(hv) (160+/-40 cm(3)), the ITV(10ph) (161+/-41 cm(3)) and the
      ITV(fb) (250+/-63 cm(3)). Mean CTV doses were between 95% and 107% of the
      prescribed dose for nearly all patients and treatment plans. Analysis of the CTV
      coverage suggested that underdosage may occur when the CT(slow) is used and a
      geographic miss occurred using the CT(fb), due to uncorrect localization of the
      average tumor position. CONCLUSIONS: The CT(hv) seems to be the optimal dataset
      for delineation, using an adequate anisotropic internal margin of (motion
      amplitude)/4.

PMID- 16971011
TI  - Randomized comparison between intracoronary beta-radiation brachytherapy and
      implantation of paclitaxel-eluting stents for the treatment of diffuse in-stent
      restenosis.
AB  - BACKGROUND AND PURPOSE: Intracoronary brachytherapy was the primary therapeutic
      option for the treatment of in-stent restenosis (ISR) during the last years.
      Especially for the treatment of diffuse ISR (lesions >10mm), beta-source
      brachytherapy was significantly superior to singular balloon angioplasty. Despite
      lacking clinical database, the implantation of drug eluting stents recently
      became a common procedure for the treatment of ISR. This randomized trial aimed
      to compare the efficacy of beta-brachytherapy with beta-radioisotopes
      (90)Sr/(90)Y and paclitaxel-eluting stent implantation for the treatment of
      diffuse ISR. MATERIAL AND METHODS: Thirty-seven patients with diffuse ISR were
      randomly assigned to beta-brachytherapy after balloon angioplasty (Beta-Cath in
      17 patients) or paclitaxel-eluting stent implantation (Taxus-Express2 in 20
      patients). Six-month clinical follow-up was obtained for all patients, while
      angiographic follow-up was available for 30 patients. RESULTS: Binary ISR
      (restenosis >50%) within target segment was observed in three patients treated
      with Beta-Cath, of which one needed target segment revascularisation for
      recurrent ISR, whereas no significant restenosis occurred in the patients treated
      with Taxus-Express2 (P=0.037). No further major adverse cardiac (target segment
      revascularisation, myocardial infarction, death) was found in either group
      (P=NS). Stent implantation was the more time-saving (31+/-11 min versus 60+/-23
      min, P<0.001) procedure. CONCLUSIONS: Although this trial revealed a significant
      reduction of binary restenosis in the Taxus-Express2 arm, we found no difference
      in clinical outcome after implantation of paclitaxel-eluting stents for the
      treatment of diffuse ISR when compared to beta-brachytherapy.

PMID- 16971012
TI  - Image-guided intensity-modulated radiation therapy for gallbladder carcinoma.
AB  - PURPOSE: Clinical and technical parameter analysis of patients treated with
      ultrasound-based image-guided tomotherapeutic IMRT for gallbladder cancer.
      METHODS AND MATERIALS: Between 8/2001 and 5/2005, 10 patients with primary tumors
      of the gallbladder were treated by image-guided IMRT to median doses of 59 Gy. To
      analyze normal tissue radiation exposure reduction using this novel approach, a
      virtual plan comparison between actually delivered IMRT plans and re-computed
      plans with identical inverse planning parameters but more conventional PTV safety
      margins was conducted. RESULTS: Average CTV was 379 cm(3), with a mean initial
      PTV of 834 cm(3). In 9/10 patients, a boost was delivered to a mean CTV(boost) of
      171 cm(3) and average PTV(boost) of 241 cm(3). One patient reported RTOG grade 3
      acute toxicity. All other patients exhibited Grade 2 or lower acute toxicity.
      Preliminary median overall survival was 16.7 months (range 3.2-34.9 months), with
      5/10 patients alive at analysis. Virtual plan comparison revealed significant
      organ-at-risk sparing by the enabled PTV margin reduction. CONCLUSION: Ultrasound
      based image-guided IMRT is a feasible mechanism of delivering conformal radiation
      doses to tumors of the gallbladder with acceptable toxicity. Early outcome data
      with this novel radiation planning and delivery technique are encouraging and
      comparable to previously reported literature.

PMID- 16971013
TI  - Cohabitation with a sick cage mate: Effects on noradrenaline turnover and
      neutrophil activity.
AB  - The present study was designed to evaluate the effects of cohabitation for 11
      days with a sick conspecific on hypothalamic levels and turnover of noradrenaline
      NA (experiment 1) and on neutrophil oxidative burst and phagocytosis in mice
      (experiment 2). Female mice were divided into two groups: control and
      experimental. One mouse of each control pair was kept undisturbed and called
      "companion of health partner" (CHP). One animal of each experimental pair of mice
      was inoculated with 5 x 10(6) Ehrlich tumor cells i.p., and the other, the
      subject of this study, was called "companion of sick partner" (CSP). In
      experiment 3, CHP and CSP mice were treated with diazepam (1.0 mg/kg) or with
      control solution (vehicle of diazepam, 1.0 mL/kg) 1h before evaluation of
      neutrophil activity. The CSP mice presented (1) decreased levels and increased
      turnover of hypothalamic NA; (2) decreased neutrophil oxidative burst after PMA
      or Staphylococcus aureus induction; (3) decreased percentage and intensity of
      neutrophil phagocytosis. In CSP mice, diazepam induced no changes in neutrophil
      oxidative burst or intensity of phagocytosis, but abolished almost completely the
      percentage of neutrophils performing phagocytosis. These data were discussed in
      the light of possible neuroimmune interactions.

PMID- 16971014
TI  - Genetic and phylogenetic analysis of multi-continent human influenza A(H1N2)
      reassortant viruses isolated in 2001 through 2003.
AB  - Genetic analyses were performed on 228 influenza A(H1) viruses derived from
      clinical subjects participating in an experimental vaccine trial conducted in 20
      countries on four continents between 2001 and 2003. HA1 phylogenetic analysis of
      these viruses showed multiple clades circulated around the world with regional
      prevalence patterns. Sixty-five of the A(H1) viruses were identified as A(H1N2),
      40 of which were isolated from South Africa. The A(H1) sequences of these viruses
      cluster with published H1N2 viruses phylogenetically and share with them
      diagnostic signature V169A and A193T changes. The results also showed for the
      first time that H1N2 viruses were prominent in South Africa during the 2001-2002
      influenza season, accounting for over 90% of the A(H1) cases in our study, and
      infecting both children (29/31) and the elderly (11/13). Phylogenetic analysis of
      the 65 H1N2 viruses we identified, in conjunction with the 56 recent H1N2 viruses
      currently available in the database, provided a comprehensive view of the
      circulation and evolution of distinct clades of H1N2 viruses in a temporal manner
      between early 2001 and mid-2003, shortly after the appearance of these recent
      reassortant viruses in or near year 2000.

PMID- 16971015
TI  - Cocksfoot mottle virus P1 suppresses RNA silencing in Nicotiana benthamiana and
      Nicotiana tabacum.
AB  - The Sobemovirus genome consists of positive sense, single-stranded polycistronic
      RNA. The 5'-terminal ORF, encoding the protein P1, is its most variable region.
      Sobemoviral P1 has been described as dispensable for replication but
      indispensable for systemic infection. The P1 of Rice yellow mottle virus-Nigerian
      isolate (RYMV-N) is the only RNA silencing suppressor reported for sobemoviruses
      until now. Using an agrobacterium-mediated transient assay, we demonstrate here
      that P1 of Cocksfoot mottle virus-Norwegian isolate (CfMV-NO) suppresses RNA
      silencing in Nicotiana benthamiana and Nicotiana tabacum, two non-host plants.
      CfMV-NO P1 was able to suppress the initiation and maintenance of silencing. The
      suppression of systemic silencing was weaker with CfMV-NO P1 than in the case of
      RYMV-N P1. In the case of suppression at the local level, the reduction in the
      amount of 25-nucleotide small interfering RNAs (siRNAs) was less pronounced for
      CfMV-NO P1 than it was when RYMV-N P1 was used. At the same time, we show that
      CfMV-NO P1 did not bind siRNAs.

PMID- 16971016
TI  - Effects of Na+/H+ exchanger inhibitors on subcellular localisation of endocytic
      organelles and intracellular dynamics of protein transduction domains HIV-TAT
      peptide and octaarginine.
AB  - Protein transduction domains such as those derived from the HIV protein TAT have
      great potential as vectors for delivery of therapeutic entities such as genes and
      proteins into cells. Extensive studies have shown that a major fraction of the
      most studied variants enters cells via an endocytic mechanism. However,
      controversy surrounds the exact uptake mechanism and whether a specific pathway
      is utilised. Studies showing inhibition of uptake of protein transduction domains
      in the presence of ion-transport inhibitors such as amiloride and its more potent
      analogue 5-(N-ethyl-N-isopropyl) amiloride (EIPA) suggest a link between peptide
      internalisation and macropinocytosis. In this study, using immunolabelling of
      early and late components of the endocytic pathway, we show that treatment of
      cells with EIPA and to a lesser extent amiloride affects the morphology and
      subcellular location of early, late endosomes and lysosomes. Enlarged early and
      late endocytic structures were observed in EIPA-treated cells, and these
      organelles accumulated in a perinuclear region. Results from experiments
      investigating the effects of EIPA on distribution of fluorescent octaarginine
      were in agreement with the immunolocalisation studies. Treatment of the CD34(+)
      leukaemia cell line KG1a with EIPA in the presence of fluorescent conjugates of
      HIV-TAT peptide and octaarginine showed distinct vesicular staining in agreement
      with untreated cells but EIPA-treated cells were additionally characterized by
      increased localization of the peptides in the cytosol. At levels previously shown
      to inhibit uptake of HIV-TAT peptide and octaarginine in other cell lines, EIPA
      was without major effect on uptake of both peptides in KG1a cells.

PMID- 16971017
TI  - Willingness to pay for health insurance among rural and poor persons: field
      evidence from seven micro health insurance units in India.
AB  - This study, conducted in India in 2005, provides evidence on Willingness to pay
      (WTP), gathered through a unidirectional (descending) bidding game among 3024
      households (HH) in seven locations where micro health insurance units are in
      operation. Insured persons reported slightly higher WTP values than uninsured.
      About two-thirds of the sample agreed to pay at least 1%; about half the sample
      was willing to pay at least 1.35%; 30% was willing to pay about 2.0% of annual HH
      income as health insurance premium. Nominal WTP correlates positively with income
      but relative WTP (expressed as percent of HH income) correlates negatively. The
      correlation between WTP and education is secondary to that of WTP with HH income.
      Household composition did not affect WTP. However, HHs that experienced a high
      cost health event and male respondents reported slightly higher WTP. The observed
      nominal levels of WTP are higher than has been estimated hitherto.

PMID- 16971018
TI  - The relation between micromotion and screw fixation in acetabular cup.
AB  - One of the major causes inducing loosening in the cementless acetabular cup
      implanting is its insufficient initial stability. In this study, three
      dimensional finite element models of the pelvis and acetabular components were
      developed to investigate the relationship between relative micromotion, initial
      stability, and screw fixation under six daily activity loadings. A commercial
      available hemispheric cup with five screw holes was used as the target acetabular
      cup. The simulation results showed that if screws were placed closed together,
      when the screw number increased from 1 to 5, the peak micromotion decreased less
      than 14%, from 126.5 to 108.8 microm, while the stable region, micromotion less
      than 28 microm, enlarged only by 40%, from 46.1% to 64.7%. However, if the screw
      could be placed near the cup rim, a single rim screw, 202.1 microm micromotion,
      could provide better stability than that of four dome screws, 209.6 microm
      micromotion, placed closed together. To conclude, multiple cup screws should be
      placed near cup rim and as separate as possible to enlarge the stable region and
      reduce the peak micromotion between cup and acetabulum.

PMID- 16971019
TI  - The coming of age of two-photon excitation imaging for intravital microscopy.

PMID- 16971020
TI  - Isolation and characterization of a novel mung bean protease inhibitor with
      antipathogenic and anti-proliferative activities.
AB  - A novel protease inhibitor, designated mungoin, with both antifungal and
      antibacterial activities, and exhibiting a molecular mass of 10kDa in SDS
      polyacrylamide gel electrophoresis, was isolated from mung bean (Phaseolus mungo)
      seeds. The isolation procedure involved a combination of extraction, ammonium
      sulfate precipitation, ion exchange chromatography on CM-Sephadex, and high
      performance liquid chromatography (HPLC) on SP-Toyopearl. Its isoelectric point
      was estimated to be 9.8 by isoelectric focusing. Its N-terminal amino acid
      sequence was determined to be EMPGKPACLDTDDFCYKP, demonstrating some resemblance
      to the C-terminal sequences of other protease inhibitors and inhibitor precursors
      from leguminous plants. It exerted a potent inhibitory action toward a variety of
      fungal species including Physalospora piricola, Mycosphaerella arachidicola,
      Botrytis cinerea, Pythium aphanidermatum, Sclerotium rolfsii and Fusarium
      oxysporum, as well as an antibacterial action against Staphylococcus aureus. In
      addition, this novel plant protease inhibitor displayed anti-proliferative
      activity toward tumor cells.

PMID- 16971021
TI  - The protective effects of omega-3 fatty acids against MK-801-induced
      neurotoxicity in prefrontal cortex of rat.
AB  - The aims of this study are to investigate the contribution effect of oxidative
      stress in MK-801-induced experimental psychosis model, and to show that
      prevention of oxidative stress may improve prognosis. Because oxidative damage
      has been suggested in the neuropathophysiology of schizophrenia, the possible
      protecting agents against lipid peroxidation are potential target for the studies
      in this field. For this purpose, Wistar Albino rats were divided into three
      groups: the first group was used as control, MK-801 was given to the rats in the
      second group and MK-801+omega-3 essential fatty acids (EFA) was given to the
      third group. MK-801 was given intraperitoneally at the dose of 0.5mg/(kgday) once
      a day for 5 days in experimental psychosis group. In the second group,
      0.8g/(kgday), omega-3 FA (eicosapentaenoic acid, 18%, docosahexaenoic acid, 12%)
      was given to the rats while exposed MK-801. In control group, saline was given
      intraperitoneally at the same time. After 7 days, rats were killed by
      decapitation. Prefrontal brain area was removed for histological and biochemical
      analyses. As a result, malondialdehyde (MDA), as an indicator of lipid
      peroxidation, protein carbonyl (PC), as an indicator of protein oxidation, nitric
      oxide (NO) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)
      activities as antioxidant enzymes, and xanthine oxidase (XO) and adenosine
      deaminase (AD) activities as an indicator of DNA oxidation was found to be
      increased significantly in prefrontal cortex (PFC) of MK-801 group (P<0.0001)
      compared to control group. In omega-3 FA treated rats, prefrontal tissue MDA, PC
      and NO levels as well as SOD, GSH-Px, XO, and AD enzyme activities were
      significantly decreased when compared to MK-801 groups (P<0.0001) whereas
      catalase (CAT) enzyme activity was not changed. Moreover, in the light of
      microscopic examination of MK-801 groups, a great number of apoptotic cells were
      observed. omega-3 FA supplementation decreased the apoptotic cell count in PFC.
      The results of this study revealed that oxidative stress and apoptotic changes in
      PFC may play an important role in the pathogenesis of MK-801-induced neuronal
      toxicity. This experimental study also provides some evidences for the protective
      effects of omega-3 FA on MK-801-induced changes in PFC of rats.

PMID- 16971022
TI  - Parkinson disease IgG and C5a-induced synergistic dopaminergic neurotoxicity:
      role of microglia.
AB  - Increasing evidence suggests the involvement of immune/inflammatory system in
      Parkinson's disease (PD). Many immune/inflammatory factors may synergistically
      participate in PD. In this study, we demonstrated that immunoglobulin G from the
      serum of 4/11 PD patients (PDIgG, 60microg/ml) and recombinant human C5a (0.1nM)
      synergistically induced selective dopaminergic neurodegeneration in rat
      mesencephalic neuron-glia cultures, while that PDIgG alone or C5a alone was
      minimally toxic or nontoxic. IgG from 17 disease controls and from 7 normal
      controls did not significantly induce dopaminergic neurotoxicity in the cultures
      even in the presence of C5a. Using mesencephalic neuron-enriched cultures, we
      found that the synergistic dopaminergic neurotoxicity was mediated by glia. The
      results from microglia-supplemented neuronal cultures, astroglia-supplemented
      neuronal cultures and neuron-astroglia cocultures indicated that microglia, not
      astroglia, played a pivotal role in the neurotoxicity. Through
      immunocytochemistry analysis and assay of proinflammatory factors, we observed
      that each of the four PDIgGs (60microg/ml) and C5a (0.1nM) synergistically
      induced microglia activation and production of superoxide and nitric oxide (NO)
      in neuron-glia cultures. Further investigations indicated that superoxide and NO
      were both responsible for the synergistic neurotoxicity. Finally, using F(ab')(2)
      fragments of PDIgG, we demonstrated that microglial Fc receptors may play an
      important role in the neurotoxicity. Our work provides new evidence for the
      involvement of the immune/inflammatory system in PD and helpful clues for
      studying the combined effect of antibody and complement on microglia.

PMID- 16971023
TI  - Malignant glioma progression and nitric oxide.
AB  - Glioblastoma multiforme, the most common of the malignant gliomas, carries a
      dismal prognosis in spite of the most aggressive therapy and recent advances in
      molecular pathways of glioma progression. Although it has received relatively
      little attention in the setting of malignant gliomas, nitric oxide metabolism may
      be intimately associated with the disease process. Interestingly, nitric oxide
      has both physiological roles (e.g., neurotransmitter-like activity, stimulation
      of cyclic GMP), and pathophysiological roles (e.g., neoplastic transformation,
      tumor neovascularization, induction of apoptosis, free radical damage). Moreover,
      whether nitric oxide is neuroprotective or neurotoxic in a given disease state,
      or whether it enhances or diminishes chemotherapeutic efficacy in malignant
      neoplasia, is unresolved. This review discusses the multifaceted activity of
      nitric oxide with particular reference to malignant gliomas.

PMID- 16971025
TI  - [Pelvic actinomycosis: two cases].
AB  - INTRODUCTION: Actinomycosis is a chronic suppurative granulomatous disease caused
      by different Actinomyces species, mostly bacillus: the Actinomyces israeli. The
      pelvis location of this infection is rare. OBSERVATIONS: We report two cases of
      actinomycosis that were diagnosed after the surgical treatment of a suspected
      ovarian tumor and a suspected acute peritonitis. Diagnosis in both cases was
      based on the histopathologic findings. CONCLUSION: The incidence of pelvic
      actinomycosis is increasing since 1960 related to the frequent use of intra
      uterine device. The clinical symptomatology is not specific, simulating a
      neoplastic or an inflammatory process. The treatment combines operative and
      antibiotic therapy.

PMID- 16971024
TI  - Learning during middle age: a resistance to stress?
AB  - Acute stressful experience enhances subsequent learning in males and impairs
      learning in females. These sex differences emerge soon after puberty in
      adulthood. Whether these opposite effects of stress on learning extend into older
      age is unknown. To examine this, young adult (2-3 months) and middle aged (17-18
      months) Fischer 344 rats of both sexes were exposed to an acute stressor of brief
      tailshocks and trained 24 h later with classical eyeblink conditioning using a
      trace paradigm. Whereas stressful experience enhanced conditioning in adult males
      and impaired conditioning in adult females, it had no effect whatsoever on
      conditioning in the aging animals of either sex. There was no effect of aging
      itself on acquisition of the conditioned response, suggesting that trace
      conditioning is not necessarily compromised during this period of life. Together,
      these data indicate that associative learning in the aging animal is resistant to
      both the negative and positive consequences of stressful experience.

PMID- 16971026
TI  - Higher pertussis hospitalization rates in indigenous Australian infants, and
      delayed vaccination.
AB  - This ecological study aimed to identify possible reasons for higher pertussis
      hospitalization rates in indigenous Australian infants. Two national datasets
      were analysed: the Hospital Morbidity Database and the Australian Childhood
      Immunisation Register (ACIR). Most (52%) pertussis hospitalizations in indigenous
      infants occurred at 0-2 months of age, and rates in these indigenous infants were
      significantly higher in remote areas. Indigenous infants had higher
      hospitalization rates and more frequently delayed vaccination than non-indigenous
      infants of the same age. These data suggest that residence in a remote area, as a
      proxy for poorer living conditions for indigenous people, and delayed
      vaccination, both contribute to higher pertussis hospitalization rates in
      indigenous infants.

PMID- 16971027
TI  - Novel codon-optimized GM-CSF gene as an adjuvant to enhance the immunity of a DNA
      vaccine against HIV-1 Gag.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent
      immunomodulatory cytokine. Here we generated a novel codon-optimized murine GM
      CSF gene as an adjuvant. The codon-optimized GM-CSF gene significantly increased
      protein expression levels in all cells tested. Although injection of the wild
      type GM-CSF plasmids adjuvanted HIV-1 Gag DNA vaccine induced detectable immune
      responses, co-administration of plasmids encoding the codon-optimized GM-CSF
      sequence with the DNA vaccine resulted in a strong antibody and CTL responses and
      a protective immune response against infection with recombinant vaccinia virus
      expressing HIV-1 Gag. This novel codon-optimized GM-CSF gene offers a practical
      molecular strategy for potentiating immune responses to vaccines as well as other
      immunotherapeutic strategies.

PMID- 16971028
TI  - Preclinical safety of recombinant human thrombin.
AB  - Recombinant human thrombin (rhThrombin) is being developed as an alternative to
      thrombin products purified from pooled human or bovine plasma, which are
      currently marketed for topical hemostasis. Preclinical studies of rhThrombin were
      conducted prior to its evaluation as a topical adjunct to surgical hemostasis in
      clinical trials. No overt clinical pathology or signs were observed in cynomolgus
      monkeys following implantation of a gelatin sponge containing either rhThrombin
      or bovine thrombin to a surgical liver wound, and similar gross and microscopic
      wound healing characteristics were observed over an eight-week recovery period
      with either compound. Repeated subcutaneous injections of rhThrombin or bovine
      thrombin to cynomolgus monkeys produced no treatment-related effects. Whereas no
      monkeys demonstrated anti-rhThrombin antibody seroconversion, specific anti
      bovine antibodies were detected in all tested monkeys exposed to bovine thrombin.
      Addition of rhThrombin or bovine thrombin to mouse fibroblast cells resulted in
      expected detachment and shape change. Topical application of rhThrombin to
      rabbits did not cause irritation to the eye, normal skin, or abraded skin. These
      studies showed that topical, subcutaneous, or implanted rhThrombin was minimally
      immunogenic, safe, and well tolerated in nonclinical models, and supported the
      clinical evaluation of rhThrombin in a variety of surgical settings.

PMID- 16971030
TI  - The association of smoking with perception of income inequality, relative
      material well-being, and social capital.
AB  - The aim of this study is to examine the association of smoking status with income
      inequality, relative deprivation, perception of relative material well-being and
      community-level social capital, controlling for individual-level indicators of
      social capital, and common socio-economic variables. Data were from telephone
      interviews of approximately 126 residents selected at random (using the
      Electronic White Pages) from each of 22 local government areas (LGAs) in the
      Melbourne metropolitan region, Victoria, Australia (total n = 2762). We used
      logistic regression to assess the association of covariates with smoking status.
      Being a smoker was associated with a higher level of perceived income inequality,
      lower perception of relative material well-being and living in a community with a
      lower degree of trust and safety. While the cross-sectional design of the study
      does not allow causal inferences, the results imply that smoking is less
      prevalent in communities that are more egalitarian and have a higher stock of
      social capital.

PMID- 16971031
TI  - Individual differences in risk perception versus risk taking: handedness and
      interhemispheric interaction.
AB  - Research indicates that right-hemisphere mechanisms are specifically sensitive to
      and averse to risk. Research also indicates that mixed degree of handedness is
      associated with increased access to right hemisphere processing. Accordingly, it
      was predicted that mixed-handers would exhibit greater risk aversion.
      Participants were presented with various risky activities and were asked to rate
      (i) the perceived risk, (ii) the perceived benefit, and (iii) their likelihood to
      engage in each activity. No handedness differences were found for any of these
      ratings. Regression analyses, however, indicated that the likelihood to engage in
      risky activities was predicted primarily by the perceived risks in mixed-handers
      and by the perceived benefits in strong-handers.

PMID- 16971032
TI  - Evaluation of the genotoxic potential of 3-monochloropropane-1,2-diol (3-MCPD)
      and its metabolites, glycidol and beta-chlorolactic acid, using the single cell
      gel/comet assay.
AB  - 3-monochloropropane-1,2-diol (3-MCPD) is a member of a group of chemicals known
      as chloropropanols. It is found in many foods and food ingredients as a result of
      food processing. 3-MCPD is regarded as a rat carcinogen known to induce Leydig
      cell and mammary gland tumours in males and kidney tumours in both genders. The
      aim of our study was to clarify the possible involvement of genotoxic mechanisms
      in 3-MCPD induced carcinogenicity at the target organ level. For that purpose, we
      evaluated DNA damages in selected target (kidneys and testes) and non-target
      (blood leukocytes, liver and bone marrow) male rat organs by the in vivo alkaline
      single cell gel electrophoresis (comet) assay, 3 and 24 h after 3-MCPD oral
      administration to Sprague-Dawley and Fisher 344 adult rats. 3-MCPD may be
      metabolised to a genotoxic intermediate, glycidol, whereas the predominant
      urinary metabolite in rats following 3-MCPD administration is beta-chlorolactic
      acid. Therefore, we also studied the DNA damaging effects of 3-MCPD and its
      metabolites, glycidol and beta-chlorolactic acid, in the in vitro comet assay on
      CHO cells. Our results show the absence of genotoxic potential of 3-MCPD in vivo
      in the target as well as in the non-target organs. Glycidol, the epoxide
      metabolite, induced DNA damages in CHO cells. beta-Chlorolactic acid, the main
      metabolite of 3-MCPD in rats, was shown to be devoid of DNA-damaging effects in
      vitro in mammalian cells.

PMID- 16971033
TI  - Safety and potential risks of enterococci isolated from traditional fermented
      capers.
AB  - A collection of 17 enterococci isolates obtained from fermentations of capers
      (the fruits of Capparis sp.) were investigated for incidence of known virulence
      determinants, antibiotic resistance and production of biogenic amines. Molecular
      identification revealed the presence of Enterococcus faecium (nine isolates),
      Enterococcus faecalis (4), E. avium (3) and Enterococcus casseliflavus/flavescens
      (1). Alpha-haemolytic activity was detected in two E. avium and one E. faecalis
      isolates, and beta-haemolytic activity was detected in E.
      casseliflavus/flavescens. The haemolytic component cylB was detected by PCR
      amplification in three non-haemolytic isolates and in E.
      casseliflavus/flavescens. The collagen adhesin ace gene and the endocarditis
      associated antigen gene efaA(fm) were detected in two isolates each. Genes
      encoding sex pheromone precursors (cpd, cob, ccf) were detected in E. faecalis
      and E. casseliflavus/flavescens. Other presumed virulence genes (agg, gelE, cylM,
      cylA and efaA(fs)) were not detected. All isolates were resistant to rifampicin,
      erythromycin and ciprofloxacin, and some were also resistant to
      quinupristin/dalfopristin, tetracycline, levofloxacin, gentamicin and
      streptomycin. Vancomycin resistance was not detected. Tyrosine decarboxylation
      was detected in all E. faecium isolates. Given the high resistance of enterococci
      to environmental conditions, and their implication in opportunistic infections,
      the incidence of potential virulent enterococci in foods (especially those of a
      higher risk-like home-made foods) should be carefully studied.

PMID- 16971034
TI  - Induction and inhibition of cytochrome P450-dependent monooxygenases of rats by
      fungicide bitertanol.
AB  - The effects of fungicide bitertanol on cytochrome P450-dependent monooxygenases
      were studied using rats treated intraperitoneally with the N-substituted triazole
      for 4 days. Treatment with 10, 25, and 100 mg/kg bitertanol produced 2-, 4-, and
      14-fold increases of 7-ethoxyresorufin O-deethylation activity in liver
      microsomes, respectively. Immunoblot analysis of microsomal proteins revealed
      that 25 mg/kg bitertanol increased CYP1A1 protein in the liver, kidney, and lung
      by 10-, 13-, and 17-fold, respectively. Bitertanol produced smaller increases of
      CYP2B and CYP3A catalytic activity and protein than that of CYP1A1 in liver. RT
      PCR analysis of total RNA indicated that bitertanol-induced CYP1A1, CYP2B, and
      CYP3A mRNA. Additions of 0.01-100 microM bitertanol to liver microsomes from rats
      treated with 25 mg/kg bitertanol or 3-methylcholanthrene inhibited microsomal 7
      ethoxyresorufin O-deethylation activity (IC(50)=0.8 or 0.9 microM). Bitertanol at
      100 mg/kg increased liver UDP-glucuronosyltransferase and glutathione S
      transferase activities by 2-fold. Bitertanol at 25 mg/kg produced a minor
      increase in metabolic activation of benzo[a]pyrene by liver S-9 fraction in the
      Ames mutagenicity test while the increase was blocked by addition of 100 microM
      bitertanol. These findings show that bitertanol is an inducer of CYP1A1, CYP2B,
      and CYP3A in vivo and an inhibitor of CYP1A catalytic activity in vitro.

PMID- 16971035
TI  - Effects of styrene and styrene oxide on glutathione-related antioxidant enzymes.
AB  - Styrene is both hepatotoxic and pneumotoxic in mice. Its mode of action is not
      clear, but it may be related to oxidative stress including a very large decrease
      in reduced glutathione (GSH). The current studies evaluated if: (1) the more
      toxic R-styrene oxide had a greater effect on reduced GSH levels than the less
      toxic S-styrene oxide, (2) the ratio of reduced to oxidized forms of glutathione
      was altered by styrene or styrene oxide, (3) other enzymes involved in the
      oxidant status of the cell, namely glutathione reductase, glutathione peroxidase
      and gamma-glutamylcysteine synthetase were altered, and (4) lipid peroxidation,
      as measured by the determination of malondialdehyde, increased. R-Styrene oxide
      (300mg/kg, ip) caused greater decreases in mouse liver and lung GSH than did S
      styrene oxide (300mg/kg, ip). Styrene (600mg/kg, ip) caused decreases in both GSH
      and GSSG in both liver and lung. Styrene and styrene oxide did not cause
      significant increases in lipid peroxidation in either liver or lung. Styrene and
      styrene oxide had minimal effects on glutathione reductase and glutathione
      peroxidase in liver and lung. Styrene increased gamma-glutamylcysteine synthetase
      activity. The results suggest that while styrene and its metabolite styrene oxide
      cause significant decreases in GSH levels, they have little effect on the enzymes
      glutathione reductase and glutathione peroxidase and that in response to
      decreased glutathione levels there is an increase in its synthesis via induction
      of gamma-glutamylcysteine synthetase activity.

PMID- 16971036
TI  - Obstetrical and gynecological writing and publishing in Europe.
AB  - OBJECTIVE: To assess the number and quality of scientific articles published by
      authors from the European Union (EU) and Germany in the field of obstetrics and
      gynecology. STUDY DESIGN: Scientific articles published during the years 1980
      2003 covered by the Journal Citation Report (JCR) were considered, with a focus
      on the impact factor (IF), authors' origin, journal country and publishing
      language. RESULTS: In 2003, there are 53 journals listed by the JCR for the field
      category 'obstetrics and gynecology', with altogether 3201 publications listed in
      the Science Citation Index (SCI). From the year 1980, the total number of
      publications increased persistently. Looking at the top 20 journals in the field
      of obstetrics and gynecology, there are 12 journals from the US, 8 from Europe.
      None of these journals has an IF>10 but 30 journals show an IF>1. Over the last
      25 years, a growing importance of the English language as scientific language can
      be observed. CONCLUSION: These data indicate an important role of European
      research in the field of obstetrics and gynecology comparable to that of US
      American research. The English language is gaining importance as scientific
      language, displacing other languages and contributing to a loss of impact of non
      English journals.

PMID- 16971037
TI  - Two-state irreversible thermal denaturation of Euphorbia characias latex amine
      oxidase.
AB  - Thermal denaturation of Euphorbia latex amine oxidase (ELAO) has been studied by
      enzymatic activity, circular dichroism and differential scanning calorimetry.
      Thermal denaturation of ELAO is shown to be an irreversible process. Checking the
      validity of two-state it really describes satisfactorily the thermal denaturation
      of ELAO. Based on this model we obtain the activation energy, parameter T(*) (the
      absolute temperature at which the rate constant of denaturation is equal to 1
      min(-1)), and total enthalpy of ELAO denaturation. HPLC experiments show that the
      thermal denatured enzyme conserves its dimeric state. The N(2)-->kD(2) model for
      thermal denaturation of ELAO is proposed: where N(2) and D(2) are the native and
      denatured dimer, respectively.

PMID- 16971038
TI  - Current status of HIFU and cryotherapy in prostate cancer--a review.
AB  - OBJECTIVES: To evaluate the current status of high-intensity focused ultrasound
      (HIFU) and cryosurgery as the primary treatment option in patients with prostate
      cancer. METHOD: A MedLine search using specified search terms was done on
      February 28, 2005. This search rendered 150 papers related to HIFU and 566 papers
      related to cryosurgery. Very few of these papers presented original outcome data
      and are included in the present review. RESULTS: No controlled trial was
      available for analysis, and no survival data were presented. No validated
      biochemical, surrogate end point was available for any of the two therapies. HIFU
      showed progression-free survival (based on prostate-specific antigen+/-biopsy
      data) of 63-87% (projected 3- to 5-yr data), but median follow-up in the studies
      ranged from 12-24 mo. Negative postoperative biopsies was seen in 82-94% of
      patients. Complications have been reduced by the combination of transurethral
      resection of the prostate and HIFU. Cryosurgery showed a progression-free
      survival of 36-92% (projected 1-7 yr data), depending on risk groups and
      definition of failure. Negative biopsies were seen in 72-87%, but no biopsy data
      were available for the currently used third-generation cryotherapy machines.
      Complications seem to be lower with the third-generation machines. CONCLUSIONS:
      None of the evaluated therapies has enough data available to support their use as
      an alternative to established therapies (surgery, radiation) for localised
      prostate cancer. Until further data become available, the use of both treatments
      should be restricted to patients unfit for established therapies who still have
      the need for local therapy.

PMID- 16971039
TI  - Larger numbers of silenced genes in cancer cell lines with increased de novo
      methylation of scattered CpG sites.
AB  - Methylation of scattered CpG sites within a CpG island (CGI), denoted as
      "methylation seeds", is proposed to serve as a precursor of dense methylation of
      the CGI. We examined whether or not an abnormal increase of methylation seeds is
      associated with a larger number of methylation-silenced genes. Two gastric cancer
      cell lines with increased seeds (AGS and KATO-III) and two cell lines without
      (HSC39 and HSC57) were treated with equivalent doses of a demethylating agent, 5
      aza-2'-deoxycytidine. Oligonucleotide microarray analysis showed that 25, 63, 9
      and 1 genes with promoter CGIs, respectively, were up-regulated at 16-fold or
      more. By methylation analysis, it was estimated that 24, 41, 4 and 1 gene,
      respectively, were silenced due to methylation of promoter CGIs. Notably, AGS and
      KATO-III had silencing of genes expressed in the normal stomach while HSC39 and
      HSC57 had few. The association between the increase of methylation seeds and
      larger numbers of silenced genes suggested that the increase can induce gene
      silencing overriding their transcription.

PMID- 16971040
TI  - Metal toxicity to Chlorella pyrenoidosa assessed by a short-term continuous test.
AB  - This study presents the metal toxicity as revealed by Chlorella pyrenoidosa using
      a short-term continuous test and the conventional batch test. Toxicity tests were
      conducted in a chemostat with a test duration of 1 day. Toxicity data of five
      different metals (Cd, Pb, Co, Ni, and Zn) derived from the continuous test were
      compared against results from the conventional batch tests. The batch test is
      characterized by its saturated nutrient status for algal growth and, on the other
      hand, the continuous test is conducted at a nutrient-limiting condition
      simulating more closely to the aquatic field environment. The continuous test
      consistently yielded smaller EC(50) values, which indicated that alga in the
      chemostat is approximately four to six times more sensitive than those from the
      batch culture. Similar phenomena between the two types of tests were observed
      based on the NOEC values. Compared to literature data (US EPA ECOTOX Database)
      from the same species of alga, differences in test sensitivity between the batch
      tests and chemostat technique varied from 9.25 to 160 times. Such distinct
      differences indicate that current toxicity database may not adequately reflect
      the impact of various metal toxicants on C. pyrenoidosa. The continuous test
      method presented herein is a sensitive and rapid assessment technique and,
      therefore, has a potential for more general applications such as routine checkup
      for regulatory purposes.

PMID- 16971041
TI  - Effects of ozonation process on lignin-derived compounds in pulp and paper mill
      effluents.
AB  - The effect of ozonation process on pulp and paper mill effluents was
      investigated. The objectives were to: (1) identify various compounds in
      wastewater from a pulp and paper mill, (2) evaluate decolorization and organic
      removal efficiency by conventional bubble reactor and (3) evaluate the
      biodegradability at various progressive stages of ozonation. The qualitative
      GC/MS analyses were performed before and after the biological treatment and
      ozonation process. Two groups of compounds were observed in this wastewater:
      lignin-derived compounds and aliphatic compounds used in the pulp and paper
      production process (i.e. n-alkanes, fatty alcohols, fatty acid and ester).
      Treatment efficiency was measured by decolorization and TOC removal rates.
      Additionally, the utilization coefficient (k) and BOD/COD ratio were determined
      to observe the biodegradability of ozonized effluents. The results indicated that
      after 45 min, the ozonation of effluents yielded almost colorless effluent with
      over 90% decolorization efficiency and with corresponding ozone capacity rate of
      20.0 mg O(3)L(-1). This decolorization was not always accompanied by the
      mineralization of the organic matters therefore ozonation was not related to TOC
      removal rates. The BOD/COD ratio increased from 0.10 to a maximum value of 0.32
      with ozone flow rate (O/F) of 4.0 L min(-1). It was confirmed by the utilization
      coefficient as first order BOD equation, the magnitude k value increased from
      0.21 day(-1) to maximum value of 0.47 day(-1) as the ozonation time was raised to
      60 min with O/F 4.0 L min(-1).

PMID- 16971043
TI  - Combustible dusts: a serious industrial hazard.
AB  - After investigating three fatal explosions in manufacturing plants, the U.S.
      Chemical Safety and Hazard Investigation Board (CSB) has concluded: The explosive
      hazard of combustible dust is not well known, and helping industry to understand
      this hazard is a priority. Prompted by these three incidents in North Carolina,
      Kentucky and Indiana and the need to increase the hazard awareness, CSB is
      conducting a study to examine the nature and scope of dust explosion risks in
      industry and to identify initiatives that may be necessary to more effectively
      prevent combustible dust fires and explosions. Such initiatives may include
      regulatory action, voluntary consensus standards, or other measures that could be
      taken by industry, labor, government, and other parties. A critical task of the
      dust study is analyzing past incidents to determine the severity of the problem
      within industry. The analysis is focusing on the number of incidents, injuries
      and fatalities, industrial sectors affected, and regulatory oversight. This paper
      presents the preliminary findings from CSBs analysis of combustible dust
      incidents over the past 25 years. This paper has not been approved by the Board
      and is published for general informational purposes only. Every effort has been
      made to accurately present the contents of any Board-approved report mentioned in
      this paper. Any material in the paper that did not originate in a Board-approved
      report is solely the responsibility of the authors and does not represent an
      official finding, conclusion, or position of the Board.

PMID- 16971042
TI  - Stabilization of nickel and chromium in sewage sludge during aerobic composting.
AB  - The speciation of heavy metals can play a major role in the toxicity of those
      metals in sewage sludge following land application. Tessier sequential extraction
      was used to investigate the changes in Ni and Cr speciation in sewage sludge
      treated by forced-aeration composting. Ni and Cr concentrations increased 30.4%
      and 36.0%, respectively, during the composting process, with H(2)O and CO(2)
      volatilization being a major contributor to the change. It was found that the
      exchangeable, carbonate-bound, Fe-Mn oxide-bound, and organic matter-bound Ni and
      Cr were transformed to residual fractions. For Cr, the carbonate-bound, Fe-Mn
      oxide-bound, and organic matter-bound fractions were major contributors, while
      organic matter-bound Ni was a major contributor to the residual fraction.
      Composting appeared to reduce Ni and Cr availability by stabilizing the two
      metals and making them more stable and less mobile.

PMID- 16971044
TI  - An experimental investigation on attentional interference by threatening
      fixations of the neck in patients with chronic whiplash syndrome.
AB  - Previous studies using a primary task procedure have demonstrated that an
      experimental pain stimulus interrupts ongoing task performance in healthy
      volunteers and patients, and that this interruption is intensified by
      catastrophic thinking about pain and the perceived threat value of the pain
      stimulus. However, no studies have investigated the interruption of attention by
      relevant threatening stimuli in specific patient samples. In the present study,
      40 patients with chronic whiplash syndrome and 40 healthy controls performed a
      primary task while simultaneously a potentially threatening neck fixation (i.e.,
      extension and rotation) was imposed. Pain catastrophizing, fear of
      movement/(re)injury, hypervigilance, and depression were assessed. The patients
      showed a more pronounced deterioration of performance compared to controls when
      the neck rotation and extension fixations were introduced. Within the groups,
      neither catastrophic thinking nor fear predicted the magnitude of the performance
      deterioration.

PMID- 16971045
TI  - Pulsed radiofrequency: a novel treatment for chronic cervical radicular pain?

PMID- 16971046
TI  - Estimation of canine intestinal parasites in Cordoba (Spain) and their risk to
      public health.
AB  - The prevalence of gastrointestinal parasites in dogs was studied in the province
      of Cordoba (southern Spain), with special attention to those parasites that can
      be transmitted to man. The experiment was completed with the examination of soil
      samples from public parks and city gardens. The study was carried out over a
      population of 1800 animals entered in the Control Animal Centre (CECA) by
      coprological methods, and within this group, 300 dogs were sacrificed and
      necropsied. The prevalence of any intestinal parasitic infection was 71.33%. The
      following parasites of the gastrointestinal tract were recorded: Isospora canis
      (22%), Isospora (Cystoisospora) spp. (10.22%), Sarcocystis (2.5%),
      Hammondia/Neospora (1.94%), Giardia canis (1%), Dipylidium caninum (13.2%),
      Taenia hydatigena (7.66%), Taenia pisiformis (4%), Uncinaria stenocephala
      (33.27%), Toxascaris leonina (14.94%), Toxocara canis (17.72%) and Trichuris
      vulpis (1.66%). Related to public health, it is important to point out the
      presence of T. canis only in puppies younger than one year and Uncinaria, more
      frequent in adult dogs. Soil samples of parks revealed the presence of eggs of
      Toxocara, and it suggests the existence of real risk for human infection.

PMID- 16971047
TI  - A 3-year field evaluation of pasture rotation and supplementary feeding to
      control parasite infection in first-season grazing cattle--effects on animal
      performance.
AB  - To evaluate non-chemical strategies to control pasture-borne parasites in first
      season grazing (FSG) cattle, a 3-year grazing trial was conducted during 2002
      2004 on naturally infected pastures on a commercial beef cattle farm in Sweden. A
      uniform pasture was divided in 4 equal 2 ha paddocks onto each of which 10, 5-9
      months old dairy breed steer calves were allocated at turn-out in May each year.
      Two strategies were evaluated: (1) turn-out onto pasture which had been grazed
      the previous year by second-season grazing (SSG) steers, followed by a move to
      aftermath in mid-July (RT) and (2) supplementation with concentrate and roughage
      for 4 weeks from turn-out (FD). Comparisons were made with an untreated (UT), and
      an anthelmintic treated control group (DO). Animal parasitology and performance
      were monitored monthly throughout the 20 weeks grazing period. Additional
      sampling occasions were performed on day 9 (for coccidia) and 10 weeks after turn
      out (mid-July). Due to clinical parasitic gastro-enteritis (PGE), salvage
      treatments were performed on all animals in group FD approximately 7 weeks after
      turn-out in 2003 and of three animals in group UT 5 weeks after turn-out in 2004.
      In 2003, the geometric mean oocyst excretion 9 days after turn-out was
      approximately 150,000 opg of mainly Eimeria alabamensis in group FD, and in 2004
      approximately 180,000 opg in group UT. Apart from the DO group, geometric mean
      faecal egg counts (FEC) were between 80 and 400 epg 4 weeks after turn-out. Mean
      serum pepsinogen concentrations (SPC) of approximately 3.6 U tyrosine were
      recorded in the FD and UT groups from late August 2002. In 2003 and 2004, mean
      concentrations in these groups were between 4.1 and 7.2 U tyrosine 8 weeks after
      turn-out. By the end of the three grazing seasons the average weight gain
      difference compared to the DO group was for FD -29, -38 and -5 kg and for RT -4, 
      21 and +14 kg, and compared to the UT group -18, +2 and +22 for FD and +7, +19
      and +41 kg for group RT. In conclusion, the rotation control strategy showed
      promising results, whereas the strategic feeding was poor from a parasite control
      standpoint.

PMID- 16971049
TI  - SSR abnormalities in chronic alcoholics.
AB  - We performed sympathetic skin response (SSR) studies on 29 male patients
      diagnosed as chronic alcoholics according to DSM-IV criteria. The average age was
      43 years and the mean duration of alcohol abuse was 21 years, with all patients
      having a history of alcohol abuse for a minimum of 4 years. None of the patients
      had any symptoms and/nor signs related to autonomic nervous system dysfunction
      and all demonstrated normal nerve conduction velocities. Hand and foot latencies
      in alcoholics were prolonged relative to controls and the difference was
      statistically significant: reflected by p values of 0.02 and 0.004, respectively.
      Forty-four percent of patients demonstrated abnormal results. The unilateral
      prolongation of the lower extremity latency was the most commonly found
      abnormality (24%). Finding abnormal SSR in this patient population has made us
      aware that SSR has the potential to detect subclinical autonomic nervous system
      dysfunction even in patients who do not have autonomic complaints or neuropathy
      and to provide information about a part of the peripheral nervous system small
      unmyelinated C fibers that can not be assessed by currently performed techniques
      used in clinical EMG laboratories or by physical examination.

PMID- 16971048
TI  - Unilateral cochlear ablation before hearing onset disrupts the maintenance of
      dorsal nucleus of the lateral lemniscus projection patterns in the rat inferior
      colliculus.
AB  - During postnatal development, ascending and descending auditory inputs converge
      to form fibrodendritic layers within the central nucleus of the inferior
      colliculus (IC). Before the onset of hearing, specific combinations of inputs
      segregate into bands separated by interband spaces. These bands may define
      functional zones within the IC. Previous studies in our laboratory have shown
      that unilateral or bilateral cochlear ablation at postnatal day 2 (P2) disrupts
      the development of afferent bands from the dorsal nucleus of the lateral
      lemniscus (DNLL) to the IC. These results suggest that spontaneous activity
      propagated from the cochlea is required for the segregation of afferent bands
      within the developing IC. To test if spontaneous activity from the cochlea also
      may be required to maintain segregated bands of DNLL input, we performed cochlear
      ablations in rat pups at P9, after DNLL bands already are established. All
      animals were killed at P12 and glass pins coated with carbocyanine dye, DiI (1,1'
      dioctodecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate), subsequently were
      placed in the commissure of Probst to label the crossed projections from both
      DNLLs. When compared with surgical controls, experimental results showed a
      similar pattern of DNLL bands in the IC contralateral to the ablated cochlea, but
      a disruption of DNLL bands in the IC ipsilateral to the cochlear ablation. The
      present results suggest that cochlear ablation after DNLL bands have formed may
      affect the maintenance of banded DNLL projections within the central nucleus of
      the IC.

PMID- 16971050
TI  - Impact of incidental bilateral salpingo-oophorectomy in a family member on breast
      cancer risk assessment: clinical considerations.
AB  - BACKGROUND: Hysterectomy (TAH/TVH) with bilateral salpingo-oophorectomy (BSO)
      remains prevalent in the general population; however, current risk tools do not
      account for the potential impact of BSO on breast cancer risk calculations in
      family members. METHODS: CancerGene software was used to estimate the effect of
      BSO in a family member on proband risk across a range of simulated family cancer
      histories. RESULTS: Impact of BSO on proband risk appears most salient when it
      occurs in a first-degree relative. Race appears to modify the attainment of
      clinically significant risk thresholds, suggesting possible systematic risk
      underestimations among black women. CONCLUSIONS: When clinicians calculate risk
      in families where a close relative had BSO, they may choose to supplement
      standard risk calculations with numerical ranges of risk that account for the
      risk-reducing effect of BSO. More consideration is needed of whether failing to
      account for BSO in risk models perpetuates race-based health disparities.

PMID- 16971051
TI  - A novel mutation detection approach of hMLH1 and hMSH2 genes for screening of
      colorectal cancer.
AB  - BACKGROUND: Recently, Denaturing High-Performance Liquid Chromatography (DHPLC)
      has been widely used for mutation detection hMLH1 and hMSH2 genes due to reduced
      cost of analysis, accuracy, and high sample throughput. Unfortunately, one major
      drawback in screening the hMLH1 and hMSH2 genes with any analysis technique
      involves sample preparation. Additionally, there are limitations to this
      technique which include: (1) amplicons for hMLH1 and hMSH2 exons cannot be
      generated under the same PCR thermal cycler condition due to differences in the
      annealing temperatures of the traditional primer sets which drastically increases
      sample preparation time; (2) due to minimal changes in the DHPLC chromatogram
      when compared to the corresponding wild-type amplicon, there is a possibility to
      not detect a homozygous mutation; and (3) lack of specialized mutation analysis
      software for automated screening of the hMLH1 and hMSH2 genes with the
      Transgenomic Wave system. METHODS: To overcome these limitations, the hMLH1 and
      hMSH2 condition-oriented-PCR primer-embedded-reactor (COPPER) plate was developed
      to reduce the sample preparation time and technological skill required for
      analysis, as well as standardize a mutation screening technique for hMLH1 and
      hMSH2 analysis using the Transgenomic Wave system for research and clinical
      genetics investigations. In this study, we validated the COPPER plate for
      simultaneous amplification of the exons of the hMLH1 and hMSH2 genes coupled to
      DHPLC detection for colorectal cancer (CRC) patients. RESULTS AND CONCLUSIONS:
      Our results suggest that the COPPER plate DHPLC approach is a simple, cost
      effective, accurate, universal, and reproducible technology for screening hMLH1
      and hMSH2 genes which are associated with human CRC. We also believe that the
      COPPER plate DHPLC approach is amenable for characterization of other germline
      alterations in clinical genetics and pharmacogenetics.

PMID- 16971052
TI  - Potassium channels: new targets in cancer therapy.
AB  - BACKGROUND: Potassium channels (KCh) are the most diverse and ubiquitous class of
      ion channels. KCh control membrane potential and contribute to nerve and cardiac
      action potentials and neurotransmitter release. KCh are also involved in insulin
      release, differentiation, activation, proliferation, apoptosis, and several other
      physiological functions. The aim of this review is to provide an updated overview
      of the KCh role during the cell growth. Their potential use as pharmacological
      targets in cancer therapies is also discussed. METHODS: We searched PubMed (up to
      2005) and identified relevant articles. Reprints were mainly obtained by on line
      subscription. Additional sources were identified through cross-referencing and
      obtained from Library services. RESULTS: KCh are responsible for some
      neurological and cardiovascular diseases and for a new medical discipline,
      channelopathies. Their role in congenital deafness, multiple sclerosis, episodic
      ataxia, LQT syndrome and diabetes has been proven. Furthermore, a large body of
      information suggests that KCh play a role in the cell cycle progression, and it
      is now accepted that cells require KCh to proliferate. Thus, KCh expression has
      been studied in a number of tumours and cancer cells. CONCLUSIONS: Cancer is far
      from being considered a channelopathy. However, it seems appropriate to take into
      account the involvement of KCh in cancer progression and pathology when
      developing new strategies for cancer therapy.

PMID- 16971053
TI  - Combined organizational and activational effects of short and long photoperiods
      on spatial and temporal memory in rats.
AB  - The present study examined the effects of photoperiod on spatial and temporal
      memory in adult Sprague-Dawley rats that were conceived and reared in different
      day lengths, i.e., short day (SD-8:16 light/dark) and long day (LD-16:8
      light/dark). Both male and female LD rats demonstrated increased spatial memory
      capacity as evidenced by a lower number of choices to criterion in a 12-arm
      radial maze task relative to the performance of SD rats. SD rats also
      demonstrated a distortion in the content of temporal memory as evidenced by a
      proportional rightward shift in the 20 and 60 s temporal criteria trained using
      the peak-interval procedure that is consistent with reduced cholinergic function.
      The conclusion is that both spatial and temporal memory are sensitive to
      photoperiod variation in laboratory rats in a manner similar to that previously
      observed for reproductive behaviour.

PMID- 16971054
TI  - Cost-effectiveness of prize-based incentives for stimulant abusers in outpatient
      psychosocial treatment programs.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of a prize-based intervention as an
      addition to usual care for stimulant abusers. METHODS: This cost-effectiveness
      analysis is based on a randomized clinical trial implemented within the National
      Drug Abuse Treatment Clinical Trials Network. The trial was conducted at eight
      community-based outpatient psychosocial drug abuse treatment clinics. Four
      hundred and fifteen stimulant abusers were assigned to usual care (N=206) or
      usual care plus abstinence-based incentives (N=209) for 12 weeks. Participants
      randomized to the incentive condition earned the chance to draw for prizes for
      submitting substance negative samples; the number of draws earned increased with
      continuous abstinence time. Incremental cost-effectiveness ratios were estimated
      to compare prize-based incentives relative to usual care. The primary patient
      outcome was longest duration of confirmed stimulant abstinence (LDA). Unit costs
      were obtained via surveys administered at the eight participating clinics.
      Resource utilizations and patient outcomes were obtained from the clinical trial.
      Acceptability curves are presented to illustrate the uncertainty due to the
      sample and to provide policy relevant information. RESULTS: The incremental cost
      to lengthen the LDA by 1 week was 258 US dollars (95% confidence interval, 191
      401 US dollars). Sensitivity analyses on several key parameters show that this
      value ranges from 163 to 269 US dollars. CONCLUSIONS: Compared with the usual
      care group, the incentive group had significantly longer LDAs and significantly
      higher costs.

PMID- 16971055
TI  - Sexual orientation, gender, and alcohol use in a cohort study of U.S. adolescent
      girls and boys.
AB  - BACKGROUND: Sexual minority youth may be at elevated risk for alcohol use
      relative to heterosexual youth, but the reasons underlying higher rates and
      whether there may be gender differences in risk are not known. METHODS: Cross
      sectional survey data from 9731 early and middle adolescent girls and boys in the
      Growing Up Today Study in 1999 were examined to assess sexual orientation and
      gender patterns in alcohol use. Multivariable regression models estimated
      associations between sexual orientation and alcohol-related behaviors, such as
      binge drinking and drinking before age 12 years. Models controlled for
      sociodemographic and psychosocial factors, with heterosexuals as the reference.
      RESULTS: Girls who described themselves as "mostly heterosexual" and
      lesbian/bisexual girls were at elevated risk compared to heterosexual girls on
      almost all alcohol-related behaviors and exposures. "Mostly heterosexual" boys
      were also at elevated risk. No significant differences in alcohol-related
      behaviors were observed between gay/bisexual and heterosexual boys. Gender-by
      sexual orientation interactions were statistically significant for LGB but not
      other orientations, indicating that lesbian/bisexual girls experienced elevated
      risk above and beyond that of gay/bisexual boys relative to same-gender
      heterosexual peers. CONCLUSIONS: In early and middle adolescence, sexual minority
      girls and "mostly heterosexual" boys experienced consistent patterns of elevated
      risk for alcohol use.

PMID- 16971056
TI  - Price and purity analysis for illicit drug: data and conceptual issues.
AB  - Data on illicit drug purity and prices are invaluable but challenging. Academic
      purists argue they are unsuitable for economic analysis [Manski, C.F., Pepper,
      J.V., Petrie, C.V., 2001. Informing America's Policy on Illegal Drugs: What We
      Don't Know Keeps Hurting Us. National Academy Press, Washington, DC], but in
      practice they are used frequently [ONDCP, 2001a. What America's Users Spend on
      Illegal Drugs. Office of National Drug Control Policy, The White House,
      Washington, DC; ONDCP, 2001b. The Price of Illicit Drugs: 1981 Through the Second
      Quarter of 2000. Office of National Drug Control Policy, The White House,
      Washington, DC; ONDCP, 2004. The Price and Purity of Illicit Drugs: 1981 Through
      the Second Quarter of 2003. Office of National Drug Control Policy, The White
      House, Washington, DC; Grossman, M., 2004. Individual behaviors and substance
      use: the role of price. Plenary Address for the 24th Arne Ryde Symposium on
      Economics of Substance Abuse at Lund University, Lund, Sweden, August 13-14,
      2004]. This paper reviews data and conceptual issues that people producing,
      analyzing, and consuming drug price and purity series should understand in order
      to reduce the likelihood of misinterpretation. It also identifies aspects of drug
      markets that are both poorly understood and relevant to some of these issues.
      They constitute a useful research agenda for health and law enforcement
      communities who would benefit from better data on the supply, availability, and
      use of illicit drugs.

PMID- 16971057
TI  - Australian clinician attitudes towards contingency management: comparing down
      under with America.
AB  - BACKGROUND: Contingency management (CM) is an efficacious treatment intervention.
      Research from the US indicates that clinicians have both positive and negative
      attitudes towards CM. Concerns about the practicalities of implementation and
      potential philosophical differences have been identified in American samples. To
      date, no research has examined Australian clinicians attitudes towards CM nor
      assessed the extent to which Australian clinicians share the concerns of American
      clinicians. METHOD: The Provider Survey of Incentives was completed by 102
      Australian drug and alcohol treatment providers. The survey assesses both
      positive and negative attitudes towards tangible and social incentives.
      Comparisons are made with published data on American samples. RESULTS: The
      proportion of respondents agreeing with positive opinions about CM in this
      Australian sample was lower than that reported in the American sample. The
      average percentage agreement for positive aspects of tangible rewards was 41%
      whereas the average percent agreement for social rewards was 51% indicating more
      positive views towards social rewards. Objections to CM were similar between the
      two samples, but American respondents more strongly agreed with the idea that it
      would not be right to give incentives when clients are still using drugs, whereas
      the Australian sample had much less difficulty with this concept. CONCLUSIONS:
      There appears to be broad support for CM from about half of the clinicians
      surveyed. The areas of concern were highly similar between the Australian sample
      and published American data. Many Australian clinicians expressed neutral views
      about CM, indicating that the environment may be ripe for implementation of
      programs.

PMID- 16971058
TI  - One session of high frequency repetitive transcranial magnetic stimulation (rTMS)
      to the right prefrontal cortex transiently reduces cocaine craving.
AB  - BACKGROUND: Cocaine dependence is a public health problem affecting 2 million
      individuals in USA. Craving is a predictor of subsequent cocaine use and is
      related to changes in brain activity in networks involving the prefrontal cortex.
      METHODS: We investigated the efficacy of one session of high frequency repetitive
      transcranial magnetic stimulation (rTMS) to reduce craving in cocaine addicted
      subjects. Six patients underwent two sessions of 10Hz rTMS over left or right
      dorsolateral prefrontal cortex (DLPFC). Before, immediately after and 4h after
      rTMS we measured craving using visual analogue scales. RESULTS: Right, but not
      left, DLPFC stimulation significantly reduced craving over time (F(2,10)=11.07,
      p=0.0029). The reduction was 19% (13.4-24.6%) from baseline and disappeared after
      4h. The interaction of time by site of stimulation for craving was also
      significant (F(2,25)=6.13, p=0.0068). CONCLUSION: One session of 10Hz rTMS over
      right, but not left, DLPFC transiently reduces craving in cocaine dependent
      individuals. These results highlight the potential of non-invasive
      neuromodulation as a therapeutic tool for cocaine addiction.

PMID- 16971059
TI  - The adoption of medications in substance abuse treatment: associations with
      organizational characteristics and technology clusters.
AB  - Despite growing interest in closing the "research to practice gap", there are few
      data on the availability of medications in American substance abuse treatment
      settings. Recent research suggests that organizational characteristics may be
      associated with medication availability. It is unclear if the availability of
      medications can be conceptualized in terms of "technology clusters", where the
      availability of a medication is positively associated with the likelihood that
      other medications are also offered. Using data from 403 privately funded and 363
      publicly funded specialty substance abuse treatment centers in the US, this
      research models the availability of agonist medications, naltrexone, disulfiram,
      and SSRIs. Bivariate logistic regression models indicated considerable variation
      in adoption across publicly funded non-profit, government-owned, privately funded
      non-profit, and for-profit treatment centers. Some of these differences were
      attenuated by organizational characteristics, such as accreditation, the presence
      of staff physicians, and the availability of detoxification services. There was
      some evidence that naltrexone, disulfiram, and SSRIs represent a group of less
      intensely regulated medications that is distinct from more intensely regulated
      medications. These types of medications were associated with somewhat different
      correlates. Future research should continue to investigate the similarities and
      differences in the predictors of medication availability across national
      contexts.

PMID- 16971060
TI  - Patterns and correlates of attempted suicide by heroin users over a 3-year
      period: findings from the Australian treatment outcome study.
AB  - In order to determine patterns and correlates of attempted suicide amongst heroin
      users across 3 years, a cohort of 387 heroin users (134 entering maintenance
      treatment, 134 entering detoxification, 81 entering residential rehabilitation
      and 38 not entering treatment) were interviewed about suicide attempts at
      baseline, 12, 24 and 36 months. Across the follow-up period, 11.6% attempted
      suicide. There were declines in the proportion who attempted suicide each year
      amongst both males and females and significant declines in Major Depression,
      suicidal ideation and current suicide plans. Despite this, levels of attempted
      suicide, suicidal ideation and Major Depression in the cohort remained higher
      than in the general population. Those who had made a previous suicide attempt
      were five times more likely to make an attempt across follow-up and there was a
      strong association between an attempt in any 1 year and increased probability of
      an attempt in the subsequent year. A quarter of those who reported suicidal
      ideation at baseline made an attempt across follow-up. At each interview point,
      current suicidal ideation was strongly associated with increased risk of a
      suicide attempt in the following year. Independent predictors of a suicide
      attempt across follow-up were a lifetime suicide history, baseline suicidal
      ideation, social isolation and the extent of baseline polydrug use. Given the
      strong predictive value of suicidal ideation and previous attempts, regular brief
      screening would appear warranted to identify those at greatest risk.

PMID- 16971061
TI  - Improvement of the secretion of extracellular proteins and isolation and
      characterization of the amylase I (amy1) gene from Ophiostoma floccosum.
AB  - UV mutagenesis was applied to improve protein secretion in Ophiostoma floccosum.
      Amylase activity was used as an indicator for enhanced protein production after
      repeated rounds of mutagenic treatment. The amylase activity in the culture
      supernatant of the best mutant (MQ.5.1) was increased by more than 240-fold
      compared to the initial parental strain. At the same time, the increase in total
      secreted protein was about six times greater than the parental strain. Secreted
      proteinase and lipase activities of the parental strain and four key mutants were
      also investigated. N-terminal sequencing of the five dominant protein bands
      separated by SDS-PAGE from the culture supernatant was conducted. Two of the
      proteins identified were subtilisin-like proteinases and one was a pepsin-like
      proteinase. In addition, one protein was identified as an alpha-amylase and one
      remained unidentified. A 6.5 kb DNA fragment was isolated by Genomic Walking PCR
      using primers based on the alpha-amylase amino acid sequence. The amplified
      fragment contained the entire gene encoding alpha-amylase (amy1) and its
      regulatory sequences. Analysis showed that multiple transcripts were generated
      from the single alpha-amylase gene locus.

PMID- 16971062
TI  - Cloning of a rat lung fibrogenic factor.
AB  - In a previous study a specific single polypeptide has been purified and
      characterized that it was capable of promoting human embryonic lung 2BS
      fibroblasts proliferation in vitro, whose N-terminal 15 amino acid have high
      sequence homology with members of the mammalian chitinase-like protein family.
      Here the cloning of the gene is reported. Its cDNA contains an open reading frame
      1421 bp long and encodes a protein with a characteristic N-terminal 21 amino acid
      endoplasmic reticulum signal peptide and the putative protein is highly
      homologous to acidic mammalian chitinase (AMCase) precursor of mouse and human.
      Recombinant proteins demonstrate chitinolytic activity, therefore the gene is
      termed as rat AMCase. Sequence analysis indicates that the gene spanned a 46.2 kb
      region in rat chromosome 2. Its expression in several tissues other than alveolar
      macrophages suggests that it might play multiple biological roles in vivo. Our
      findings will facilitate studies on its roles in physiological and pathological
      processes.

PMID- 16971063
TI  - A new perspective on isochore evolution.
AB  - The genomes of mammals and birds show dramatic variation in base composition over
      large scales, the so called isochore structure of the genome. The origin of
      isochores is still controversial: various neutral and selectionist models have
      been proposed--and criticized--since the discovery of isochores in the 1970s. The
      availability of complete mammalian genomes has yielded new opportunities for
      addressing this question. In particular, it was recently proposed that (i) the
      isochore structure is declining in many mammalian groups, and that (ii) GC
      content is influenced by local recombination rate, possibly via the mechanism of
      GC-biased gene conversion. In this article we review the existing support for
      these two hypotheses, and discuss how they can be combined to provide a new
      perspective on isochore evolution.

PMID- 16971064
TI  - Identification and characterization of lin-28 homolog B (LIN28B) in human
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide.
      Several studies have identified signature gene sets that may be useful as
      potential diagnostic tools by global microarray analysis. Here we report the
      cloning and characterization of a novel gene, lin-28 homolog B (LIN28B), which is
      overexpressed in hepatocellular carcinoma. The heterochronic gene lin-28 is a key
      regulator of developmental timing in the nematode Caenorhabditis elegans. Similar
      with lin-28 proteins, LIN28B conserves a cold shock domain and a pair of CCHC
      zinc finger domains. Phylogenetic analysis suggests that they might arise as a
      result of duplication from an ancestral gene. Overexpression of LIN28B was noted
      in most HCC cell lines and clinical samples. By western blot analysis using a
      polyclonal antibody against LIN28B, a short LIN28B isoform was also identified in
      non-tumor liver tissue and fetal liver. Although predominantly localized in the
      cytoplasm, we found that LIN28B protein shows cell cycle-dependent nuclear
      translocation in Huh7 cells. Induced expression of exogenous LIN28B in a tet-off
      cell line promoted cancer cell proliferation. Interestingly, the segment of the
      unusually long 3'UTR of LIN28B contains complementary sites to let-7 microRNA of
      mammals. And our studies provided indirect evidence that LIN28B is a possibly
      natural target for let-7 mediated regulation. These findings strongly implicate a
      critical role of LIN28B during development and tumorigenesis and suggest a
      possible novel mechanism.

PMID- 16971065
TI  - Comparison of BACTEC 460 and MGIT 960 systems for the culture of Mycobacterium
      avium subsp. paratuberculosis S strain and observations on the effect of
      inclusion of ampicillin in culture media to reduce contamination.
AB  - To compare the utility and diagnostic accuracy of BACTEC and MGIT culture
      systems, a total of 41 pooled faecal samples, each containing faeces from one
      sheep infected with the S strain of Mycobacterium paratuberculosis and four
      uninfected sheep was cultured. The MGIT culture system did not support the growth
      of the S strain of M. paratuberculosis from faeces within the time frame of the
      experiments, although a laboratory adapted S strain grew slowly in MGIT provided
      that sufficient bacteria were inoculated. In contrast, C strain grew rapidly in
      MGIT. The sensitivity of culture was calculated relative to the infection status
      of the animals, none of which had clinical signs of ovine Johne's disease. The
      overall sensitivity of pooled faecal culture in the BACTEC culture system was
      21.9% (95% confidence limits, 10.5-37.6), a figure dependant on the proportion of
      multibacillary cases. The sensitivities of the BACTEC culture system for pools
      containing animals with multibacillary and paucibacillary lesions were 100.0%
      (95% confidence limits, 47.2-100.0) and 17.8% (95% confidence limits 6.06-36.8),
      respectively. The contamination rate of BACTEC cultures was 9.7% compared to
      14.3% for MGIT. The effect of 100 microg/ml ampicillin on the S strain of the M.
      paratuberculosis was examined and in both BACTEC and MGIT media it delayed growth
      by about 1 week. The composition of MGIT medium, particularly presence of
      vancomycin hydrochloride, slowed the growth of the S strain. The low content of
      egg yolk was considered to be another possible factor. The radiometric BACTEC
      culture system remains the best alternative for the culture of S strain and is
      recommended in circumstances where the genotype (s) of the strains present in a
      region/farm is either unknown or S strain.

PMID- 16971066
TI  - Phenotypic and genotypic differentiation of porcine Salmonella enterica subsp.
      enterica serovar Derby isolates.
AB  - Sixty-two Salmonella enterica subsp. enterica serovar Derby isolates from
      slaughter pigs and meat products isolated in Southern Brazil were analyzed for
      their genomic relationships and for the presence of antimicrobial resistance
      genes. Twenty-four S. Derby isolates were indistinguishable by their subtracted
      restriction fingerprinting (SRF) pattern, XbaI- and BlnI-macrorestriction
      patterns, phage type, plasmid profile, and resistance pattern. In contrast to the
      BlnI-macrorestriction patterns, the XbaI-macrorestriction patterns were in good
      agreement with the results of SRF analysis and phage typing. Among the four phage
      types detected, PT10 and PT21 were the most common. The combination of all typing
      methods revealed a great diversity among the S. Derby isolates. All strains
      carried plasmids and the 60 resistant isolates showed at least tetracycline
      resistance. The resistance genes found were sul1 and/or sul2 (sulfonamide
      resistance), aadA2 (streptomycin/spectinomycin resistance), tet(A) (tetracycline
      resistance), tet(B) (tetracycline/minocycline resistance), bla(TEM) (ampicillin
      resistance), and dfrA14 (trimethoprim resistance). A correlation of the geno- and
      phenotypic characteristics with the origin of the isolates revealed a substantial
      temporal variation in the occurrence of specific S. Derby isolates in different
      independent pig production lines in Southern Brazil. The large number of
      resistant isolates underlined the potential risk that S. Derby isolates can pose
      to human health when they enter the food chain.

PMID- 16971067
TI  - Characteristics of an outbreak of West Nile virus encephalomyelitis in a
      previously uninfected population of horses.
AB  - Equine West Nile virus (WNV) encephalomyelitis cases - based on clinical signs
      and ELISA serology test results - reported to Texas disease control authorities
      during 2002 were analyzed to provide insights into the epidemiology of the
      disease within a previously disease-free population. The epidemic occurred
      between June 27 and December 17 (peaking in early October) and 1,698 cases were
      reported. Three distinct epidemic phases were identified, occurring mostly in
      southeast, northwest and then central Texas. Significant (P<0.05) disease
      clusters were identified in northwest and northern Texas. Most (91.1%) cases had
      no recent travel history, and most (68.9%) cases had not been vaccinated within
      the previous 12 months. One-third of cases did not survive, 71.2% of which were
      euthanatized. The most commonly reported presenting signs included ataxia (69%),
      abnormal gait (52%), muscle fasciculations (49%), depression (32%) and recumbency
      (28%). Vaccination status, ataxia, falling down, recumbency and lip droop best
      explained the risk of not surviving WNV disease. Results suggest that the peak
      risk period for encephalomyelitis caused by WNV may vary substantially among
      regions within Texas. Recumbent horses have a poor prognosis for survival.
      Vaccines, even if not administered sufficiently in advance of WNV infection
      within a district, may reduce the risk of death by at least 44%.

PMID- 16971068
TI  - Development of a real time PCR for the detection of Taylorella equigenitalis
      directly from genital swabs and discrimination from Taylorella asinigenitalis.
AB  - A discriminatory real time PCR for the detection of Taylorella equigenitalis, the
      causative agent of contagious equine metritis (CEM), and the related species T.
      asinigenitalis was developed for the direct examination of genital swabs. The
      112bp amplicons produced from the two species were discriminated from each other
      using TaqMan probes labelled with different fluorophores. The TaqMan PCR was
      shown to be specific for the 16S ribosomal DNA of the two species of taylorella
      and did not cross-hybridise with the 16S ribosomal DNA of other bacteria tested.
      Direct amplification from genital swabs was shown to be equally sensitive to that
      of culture methods. Prevalence in a sample set from The Netherlands was shown to
      be equivalent to that demonstrated by culture. A companion real time PCR that
      amplified a fragment of the 16S rDNA gene of equine commensal bacteria was
      developed to ensure bacterial DNA was extracted from swab material supplied for
      testing. The use of a rapid and reliable real time PCR for the organism causing
      CEM should aid the control of this disease.

PMID- 16971069
TI  - Hydrolysis of an acetylthiocholine by pralidoxime iodide (2-PAM).
AB  - Pralidoxime iodide (2-PAM), an antidote approved for the reactivation of
      inhibited acetylcholinesterase (AChE) in organophosphate poisoning, dose
      dependently hydrolyzed an acetylthiocholine iodide (ASCh). The AChE (0.3 U)
      activity inhibited by VX analog (ENMP, 0.1 microM) increased to approximately
      200% of normal levels after a dosage of 5 mM 2-PAM (control 0.132+/-0.012 U/ml, 5
      mM 0.253+/-0.026 U/ml). This result indicates that 2-PAM produced a thiocholine
      from the ASCh by hydrolysis. High-performance liquid chromatography (HPLC)
      analysis was then performed to further clarify the hydrolysis of ASCh with 2-PAM.
      It was clear that 2-PAM was converted to acetylated 2-PAM with acetic acid
      produced from ASCh by hydrolysis. Next, we tried to compare this esterase-like
      activity of 2-PAM with that of obidoxime, which is known as a strong reactivator
      of inhibited AChE, and with diacetylmonoxime, known as a weak reactivator. All of
      these oximes showed esterase-like activity, and their strengths were consistent
      with those of known reactivators of inhibited AChE. These results indicate that a
      great deal of the data obtained previously with ASCh relating to the effects of
      oximes must be rechecked. It is clear that oximes easily hydrolyze ASCh. We
      therefore strongly caution that the method of determining AChE activity with ASCh
      is not suitable for examining the effects of oximes.

PMID- 16971070
TI  - Relationship between bovine fertility and the number of spermatozoa penetrating
      the cervical mucus within straws.
AB  - In this study, by using a recently developed test technique, the relationship
      between the total spermatozoa number penetrating determined sites of bovine
      cervical mucus in straws and potential fertility of bulls, and other
      spermatological characteristics were investigated. Furthermore, we aimed to
      determine the effect on the test results, of two different incubation
      temperatures (37 and 41 degrees C) and two sperm penetration distance ranges
      (PDRs). Frozen semen samples of six Holstein bulls were used in the study. The
      bulls were divided into two fertility groups (high and low fertility) according
      to the "non-return rates" (NRR). For the penetration test, cervical mucus was
      drawn into transparent plastic straws and incubated with semen at 37 and 41
      degrees C for 15 min. After the incubation, straws were frozen in liquid nitrogen
      vapour and stored at -20 degrees C. On the evaluation day, concentrations of
      spermatozoa penetrated to the PDRs, each of which was 2.5 mm, between 32.5 and 35
      mm (first penetration distance range, PDR1), and 50 and 52.5 mm (second
      penetration distance range, PDR2) distance in the straws from the open end, were
      measured. When compared with the low fertility group, bulls from the high
      fertility group showed a higher number of spermatozoa at the determined PDRs, and
      a significant positive correlation was found between the total number of
      spermatozoa at the penetration distances and the NRR scores of the bulls.

PMID- 16971071
TI  - Influence of macro and micro minerals in the peri-parturient period on fertility
      in dairy cattle.
AB  - Infertility in dairy cattle is a complex, multi-factorial problem that cannot be
      evaluated in isolation of other diseases and disorders. Clearly there is a role
      for the prevention of problems in the peri-parturient period, in particular
      hypocalcaemia, mastitis, lameness and retained placenta (RP), that all have a
      negative impact on the subsequent fertility of the cow. Minerals, trace elements
      and vitamins play a vital role in the prevention of these disorders at this time.
      Macro minerals are involved in the acid base status of the dairy cow and
      influence calcium metabolism. The use of anionic salts in combination with
      adequate calcium and magnesium supplementation may help to improve dry matter
      intakes and reduce negative energy balance in the post-calving period as well as
      prevent hypocalcaemia. Vitamin E and zinc are effective in prevention of mastitis
      that occurs predominantly in the first weeks of lactation, through enhanced
      antioxidant function and keratinisation of the teat canal. Lameness in dairy
      cattle also occurs mainly in lactation though most of the original insults to the
      hoof can occur prior to calving. Zinc and biotin are implicated in improving
      keratinisation of the hoof and prevention of this disease. Organic forms of zinc
      are retained better than inorganic sources and may provide greater benefit in
      disease prevention. Retained placenta can be reduced by prevention of
      hypocalcaemia and also adequate selenium status of the dairy cow. Selenium yeast
      is known to have higher retention in tissues and may play an important role in
      ensuring sufficient selenium is available to the cow for reduction of disease.

PMID- 16971072
TI  - Comparison of biochemical parameters of Muscovy drake semen diluted and stored at
      4 degrees C in three buffers.
AB  - A comparison study of biochemical parameters of semen from Muscovy drakes diluted
      and stored at 4 degrees C in three buffers--IMV-buffer (France), HIA-1 and AU
      (Bulgaria) was carried out. The ejaculates were collected twice a week from ten 1
      year-old Muscovy drakes using laying Muscovy females as teaser. Semen was diluted
      immediately, respectively, with IMV-buffer, HIA-1 and AU, and cold-stored (4
      degrees C) for 1, 3 and 6h. The intensities of oxygen uptake at the third hour in
      semen diluted, respectively, with IMV-buffer (200+/-1.6 nAO/10(9) spermcellsmin),
      with HIA (224+/-44 nAO/10(9) spermcellsmin) and with AU (238+/-48 nAO/10(9)
      spermcellsmin) were highly significant in comparison with neat semen (75+/-0.7
      nAO/10(9)spermcellsmin). The observed intensity of fructolysis was highest when
      using AU, followed by HIA-1 and IMV-buffer. During the first hour of storage the
      level of pyruvic acid was significantly lower in semen diluted with Bulgarian
      extenders, and this stability for AU referred to the entire period. For lactic
      acid, the differences were not statistical significant. Our investigations do not
      show significant differences concerning the dynamics of inorganic phosphate and
      total lipids after dilution with all tested extenders. On the contrary, high
      increase of cholesterol efflux from spermatozoa to seminal plasma-diluents were
      obtained after 6 h of storage. All extenders, IMV-buffer (France), HIA-1 and AU
      (Bulgaria) for diluting and short time storage of semen from Muscovy drakes at 4
      degrees C maintain the necessary comfort of energy metabolism of the spermatozoa.

PMID- 16971073
TI  - Rupture and drug release characteristics of multi-reservoir type microspheres
      with poly(dl-lactide-co-glycolide) and poly(dl-lactide).
AB  - For the multi-reservoir type microspheres composed of polylactide (PLA) and
      poly(dl-lactide-co-glycolide) (PLGA), the influence of inner drug-holding
      layer/outer layer ratio on drug release profiles was studied. The microspheres
      were prepared by the O/W type emulsion-solvent evaporation technique, and
      cisplatin was used as a model drug. The water-uptake and the erosion of each
      polymer were evaluated to clarify the mechanism of drug release for multi
      reservoir type microspheres. The formulations were classified by the influence of
      the blending ratio on drug-release profiles: the formulations with the drug
      release profiles independent of the blending ratio (Typel group) and the
      formulations with drug-release profiles depending on the blending ratio (type 2
      group). The formulations of type 1 group showed the uniform swelling during drug
      release test, and provided the drug-release governed by the erosion of the inner
      drug-holding layer. On the other hand, the formulations of Type2 group showed the
      rupture of outer layer which was induced by the swelling of inner drug-holding
      layer, and the microspheres with the low ratio of the PLGA provided the drug
      release rate which exceeded the estimate from the erosion profiles. The results
      of present study revealed that two types of drug-release mechanism exist for
      multi-reservoir type microspheres.

PMID- 16971074
TI  - Degradation behaviour of microspheres prepared by spray-drying poly(D,L-lactide)
      and poly(D,L-lactide-co-glycolide) polymers.
AB  - Polymeric microsphere degradation must be taken into account in the design of
      drug delivery systems to be injected in in vivo systems, thus a prior analysis of
      in vitro degradation behaviour of microspheres appears to be necessary. In this
      study degradation characteristics of poly(lactide-co-glycolide) (PLGA) and
      poly(D,L-lactide) (PLA) microspheres prepared by the spray-drying technique have
      been examined. It was found that a slow decrease in molecular weight took place
      during the first stage of degradation, and the value of the rate constant
      decreased with the increase of the percentage of lactic acid of the polymer in a
      linear way. Thus, the period of time of this first stage decreased with the
      increase of content of glycolidyl units of the polymer, and it was the unique
      stage observed in PLA microspheres after 5 months of study. During this period of
      time, significant mass loss was not observed in the microspheres. The second
      stage of degradation of PLGA microspheres showed a larger rate constant, whose
      value increased with the content of glycolidyl units of the polymer. Mass loss
      was observed from number-average molecular weight about 6000. A sharp decrease of
      glass transition temperature (T(g)) was observed coinciding with the start of
      mass loss. This fact was accompanied by a physical change of the samples, fusion
      of microspheres to form large particles, which also fusion to form a unique mass
      of polymer; moment from that the degradation process was quicker.

PMID- 16971075
TI  - Supercritical antisolvent precipitation of PHBV microparticles.
AB  - The micronization of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) from
      organic solutions using supercritical antisolvent (SAS) technique has been
      successfully achieved. SAS experiments were carried out at different operational
      conditions and microspheres with mean diameters ranging from 3 to 9 microm were
      obtained. The effect of CO(2) and liquid flow, temperature and pressure on
      particle size and particle size distribution was evaluated. The microspheres were
      precipitated from a dichloromethane (DCM) solution. The best process conditions
      for this mixture were, according to our study, 40 degrees C, 100 bar, 1 mL min(
      1) liquid flow and 10 L min(-1) carbon dioxide flow. Experiments with polymers
      containing different HV percentages were carried out. The powders obtained became
      more spherical as the HV content decreased.

PMID- 16971076
TI  - Antimicrobial activity of the methanolic extracts and compounds from Vismia
      laurentii De Wild (Guttiferae).
AB  - Methanolic extracts prepared from the leaves, twigs and the roots of Vismia
      laurentii De Wild as well as nine compounds isolated from these crude extracts,
      were tested for their antimicrobial activity against Gram-positive bacteria (six
      species), Gram-negative bacteria (12 species) and two Candida species using disc
      diffusion and well micro-dilution methods. The disc diffusion assay indicated
      that the crude extract was active against all the pathogens tested, whereas
      isolated compounds showed selective activities. The degree of sensitivity of the
      test organisms to purified compounds varied from 25 to 90%. Fridelin (8) was
      found to be the most active compound, while Bivismiaquinone (3) was the least
      active. The lowest minimum inhibition concentration (MIC) values as obtained by
      the micro-dilution assays were 19.53 and 1.22 microg/ml for the crude extracts
      and purified compounds, respectively. The lowest value for the purified compounds
      (1.22 microg/ml) was obtained with O(1)-demethyl-3',4'-deoxypsorospermin-3',4'
      diol (6) on Candida gabrata and Bacillus subtilis; 1,8-dihydroxy-6-methoxy-3
      methylanthraquinone (5) on Bacillus subtilis and 6-deoxyisojacareubin (7) on
      Bacillus stearothermophilus. These results provide promising baseline information
      for the potential use of these crude extracts as well as some of the isolated
      compounds in the treatment of bacterial and fungal infections.

PMID- 16971077
TI  - Anti-proliferative effect of Euphorbia stenoclada in human airway smooth muscle
      cells in culture.
AB  - The ethanolic extract of a Malagasy species Euphorbia stenoclada (ES)
      (Euphorbiaceae), traditionally used as a herbal remedy against asthma and acute
      bronchitis, was tested to evaluate possible anti-proliferative activity on human
      airway smooth muscle cells (HASMC). The ES ethanolic extract totally abolished
      the interleukin-1beta (IL-1beta) induced proliferation of HASMC (IC(50)=0.73+/
      0.08 microg/mL). No cytotoxic effect was observed up to 20 microg/mL. A bioassay
      guided fractionation of the ethanolic extract was performed by reversed-phase
      (RP) flash chromatography, giving five fractions (FA to FE) where fraction FE was
      the only active one (IC(50)=0.38+/-0.02 microg/mL). The purification of this
      bioactive fraction FE was carried out by RP-HPLC affording six sub-fractions 1-6,
      and only sub-fraction 5 kept the anti-proliferative activity. Its major
      constituent was identified as quercetin (IC(50)=0.49+/-0.12 microg/mL) by means
      of HPLC/UV/MS and co-elution with the authentic standard. Quercitrin was also
      identified in the fraction FE but was inactive. A structure-activity relationship
      with flavonols determined that methylation reduced the anti-proliferative
      activity whereas glycosylation abolished it. The present study shows that the
      anti-proliferative properties of Euphorbia stenoclada are mediated through the
      presence of quercetin that may explain the traditional use of this plant as a
      remedy against asthma.

PMID- 16971078
TI  - Acute osteomyelitis, septic arthritis and discitis: differences between neonates
      and older children.
AB  - There are aetiological, clinical, radiological and therapeutic differences
      between musculoskeletal infection in the neonate (and infant) and in older
      children and adults. Due to the anatomy and blood supply in neonates,
      osteomyelitis often co-exists with septic arthritis. Discitis is more common in
      infants whereas vertebral body infection is more common in adults. This review
      article discusses the important clinical and radiological differences that in the
      past have led many authors to consider neonatal osteomyelitis a separate entity
      from osteomyelitis in the older child.

PMID- 16971079
TI  - The evidence for cerebral protection: an analysis and summary of the literature.
AB  - It has been considered likely that the majority of cerebral ischaemic episodes
      following carotid artery stenting are due to cerebral embolisation. It is
      intuitive therefore, to attempt to prevent these presumptive emboli, whether they
      are comprised of air or formed elements, from reaching the brain. Various
      pharmacological and mechanical solutions are being used. The available literature
      is hampered by comparisons against historical controls of unprotected CAS with
      many confounding variables that may influence outcome. There is no clinical Level
      I evidence to support the use of protection devices but Level-III and Level-IV
      evidence suggest benefit.

PMID- 16971080
TI  - Phylogenetic position of Salinibacter ruber based on concatenated protein
      alignments.
AB  - A total of 22 genes from the genome of Salinibacter ruber strain M31 were
      selected in order to study the phylogenetic position of this species based on
      protein alignments. The selection of the genes was based on their essential
      function for the organism, dispersion within the genome, and sufficient
      informative length of the final alignment. For each gene, an individual
      phylogenetic analysis was performed and compared with the resulting tree based on
      the concatenation of the 22 genes, which rendered a single alignment of 10,757
      homologous positions. In addition to the manually chosen genes, an automatically
      selected data set of 74 orthologous genes was used to reconstruct a tree based on
      17,149 homologous positions. Although single genes supported different
      topologies, the tree topology of both concatenated data sets was shown to be
      identical to that previously observed based on small subunit (SSU) rRNA gene
      analysis, in which S. ruber was placed together with Bacteroidetes. In both
      concatenated data sets the bootstrap was very high, but an analysis with a
      gradually lower number of genes indicated that the bootstrap was greatly reduced
      with less than 12 genes. The results indicate that tree reconstructions based on
      concatenating large numbers of protein coding genes seem to produce tree
      topologies with similar resolution to that of the single 16S rRNA gene trees. For
      classification purposes, 16S rRNA gene analysis may remain as the most pragmatic
      approach to infer genealogic relationships.

PMID- 16971081
TI  - Reduction of carry-over in column-switching HPLC/MS system with automated system
      washing procedure for highly sensitive direct analysis of donepezil in dog
      plasma.
AB  - To solve the problem of carry-over--a persistent chromatographic challenge for
      bioanalytical assays with highly sensitive detector such as a mass spectrometry
      (MS)--a new on-line sample pretreatment HPLC/MS system using a column-switching
      technique was established. This system was designed to reduce carry-over based on
      a hydrophobic interaction mechanism using a washing function (multi-mobile phase
      flow system), as well as to remove impurities on-line in a mobile phase for the
      pretreatment. As a result, a washing function in this system was enabled to
      reduce carry-over and to remove impurities in a mobile phase by automatic
      operation. Therefore, concentration levels of donepezil (DH) in dog plasma as low
      as 10 pg/mL could be determined using this on-line sample pretreatment HPLC/MS
      system. In addition, method validation results of specificity, linearity,
      accuracy, precision, lower limit of quantitation (LLOQ), and carry-over
      demonstrated that this on-line sample pretreatment HPLC/MS system was robust and
      valid as a practical assay of drugs and metabolites in the biological samples.

PMID- 16971082
TI  - A liquid chromatography/tandem mass spectrometry assay to quantitate MS-275 in
      human plasma.
AB  - A rapid, sensitive and selective method was developed and validated using
      LC/MS/MS for determination of MS-275 in human plasma. Sample preparation involved
      a single step liquid-liquid extraction by the addition of 0.2 ml of plasma with 5
      ml acetonitrile/n-butyl-chloride. Separation of the compounds of interest,
      including the internal standard paclitaxel, was achieved on a Waters X-Terra
      C(18) (50 mm x 2.1mm i.d., 3.5 microm) analytical column using a mobile phase
      consisting of acetonitrile/ammonium acetate (pH 2.9; 2mM)(60:40, v/v) containing
      0.1% formic acid and isocratic flow at 0.15 ml/min for 3 min. The analytes were
      monitored by tandem-mass spectrometry with electrospray positive ionization.
      Linear calibration curves were generated over the range of 0.5-100 ng/ml with
      values for the coefficient of determination of >0.99. The values for both within
      day and between day precision and accuracy were well within the generally
      accepted criteria for analytical methods (<15%). This method was subsequently
      used to measure concentrations of MS-275 in cancer patients receiving an oral
      weekly dose of 4 mg/m(2).

PMID- 16971083
TI  - High-performance liquid chromatographic method for the quantification of
      phenolics in 'Chyavanprash' a potent Ayurvedic drug.
AB  - Quantification of bioactive principles through modern analytical tools is
      essential for establishing the authenticity, credibility, prescription and usage
      of Ayurvedic medicines/herbal formulations. 'Chyavanprash' is one of the oldest
      and most popular Ayurvedic preparations, used widely as a health promotive and
      disease preventive 'Rasayana' drug in India and elsewhere. The rejuvenating and
      tonic properties of 'Chavanprash' are considered mainly due to their antioxidant
      principles, which in turn is due to the presence of phenolic compounds. A simple
      high-performance liquid chromatography (HPLC) method for the separation and
      quantitative determination of the major antioxidant compounds from 'Chyavanprash'
      has been developed. The use of Waters Symmetry column and an acidic mobile phase
      enabled the efficient separation of phenolic compounds (catechin, quercetin-3-O
      rutinoside, syringic acid and gallic acid) within a 35 min analysis. Validation
      of the method was done with a view to demonstrate its selectivity, linearity,
      precision, accuracy and robustness. In addition optimization of the complete
      extraction of phenolic compounds were also studied.

PMID- 16971084
TI  - Improvement of an enzyme linked lectin assay to determine recombinant mistletoe
      lectin I.
AB  - Extracts from Viscum album leaves, with mistletoe lectin I (ML I) as the main
      therapeutic agent, are commonly used as an immunomodulating adjuvat in tumour
      therapy. Because of its popularity against cancer and the possibility for a
      better standardisation a recombinant ML I (rML I) was developed by Eck et al. To
      improve the sensitivity of an already established enzyme linked lectin assay
      (ELLA) for rML I human haptoglobins with different phenotypes (1.1, 2.1 and 2.2)
      are used to replace asialofetuin as matrix. To determine the carbohydrate binding
      specificity of the tested glycoproteins the ELLA was realised in the presence of
      the competitive carbohydrate beta-d-lactose. It could be shown that using
      haptoglobin phenotype 1.1 instead of asialofetuin improved the test results
      markedly. Both, the limit of detection and the limit of quantitation were
      decreased by an order of magnitude. However, this positive result was obviously
      accompanied by a loss in specificity of the test. The specificity of asialofetuin
      for rML I is almost six-fold higher than for the tested haptoglobins. Thus, in
      cases where high specificity and less sensitivity values for rML I is required
      the ELLA should still be run with asialofetuin as binding partner.

PMID- 16971086
TI  - Impurity profiling of atropine sulfate by microemulsion electrokinetic
      chromatography.
AB  - An oil-in-water microemulsion electrokinetic chromatography (MEEKC) method has
      been developed and validated for the determination of atropine, its major
      degradation products (tropic acid, apoatropine and atropic acid) and related
      substances from plants material (noratropine, 6-hydroxyhyoscyamine, 7
      hydroxyhyoscyamine, hyoscine and littorine). Separation of atropine and all
      impurities was optimized by varying the voltage, the nature of the oil droplet
      and the buffer, as well as the organic modifier (methanol, 2-propanol or
      acetonitrile) and the surfactant type and concentration. The optimum O/W
      microemulsion background electrolyte (BGE) solution consists of 0.8% (w/w)
      octane, 6.62% (w/w) 1-butanol, 2.0% (w/w) 2-propanol, 4.44% (w/w) SDS and 86.14%
      (w/w) 10 mM sodium tetraborate buffer pH 9.2. In order to shorten the analysis
      time a voltage gradient was applied. The validation was performed with respect to
      specificity, linearity, range, limit of quantification and detection, precision,
      accuracy and robustness. The established method allowed the detection and
      determination of atropine sulfate related substances at impurity levels given in
      the European Pharmacopoeia. Good agreement was obtained between the established
      MEEKC method and the traditional RP-HPLC method.

PMID- 16971085
TI  - Determination of neomycin and bacitracin in human or rabbit serum by HPLC-MS/MS.
AB  - The method for the simultaneous determination of neomycin and bacitracin in human
      or rabbit serum was developed by using ion pairing reversed phase chromatography
      and tandem mass spectrometry (MS/MS) detection with electrospray (ESI) in
      positive mode. Both substances elute under these conditions at the same time and
      also kanamycin as internal standard elutes almost at the same time. The sample
      preparation was simple-only using 0.1 mL serum by protein precipitation with
      acetonitrile. Neomycin and bacitracin were detected as two-fold charged ions as
      well as the internal standard. The calibration range of these quite difficult
      detectable substances was 0.2-50 microg/mL of serum. The method was validated for
      both human or rabbit serum. The inter batch precision of quality control samples
      in human serum for neomycin ranged from 4.46% to 8.99% and for bacitracin from
      6.85% to 11.17%. The inter batch accuracy for neomycin ranged from 98.7% to
      100.7% and for bacitracin from 99.2% to 103.0%. At lower limit of quantitation
      (LLOQ) level of 0.2 microg/mL inter batch precision in human serum for neomycin
      was 12.05% and for bacitracin 11.91%, whereas accuracies were 99.9% for neomycin
      and 102.7% for bacitracin. Bench top stability in human or rabbit serum was given
      over three freeze thaw cycles and 4h at room temperature. The method can be
      considered to be specific and recoveries for sample preparation were high.

PMID- 16971087
TI  - Development and validation of a quantitative cell-based bioassay for comparing
      the pharmacokinetic profiles of two recombinant erythropoietic proteins in serum.
AB  - An in vitro cell-based bioassay was developed and validated to assess the
      pharmacokinetic profiles of two novel therapeutic recombinant proteins (EP1 and
      EP2) with erythropoiesis stimulating properties in Sprague-Dawley rats. While
      immunoassays are the standard choice for evaluating the pharmacokinetic
      parameters of drugs, no immunoassay was available for EP2, necessitating the need
      for a quantitative bioassay capable of measuring both EP1 and EP2 separately so
      that appropriate comparisons could be made. The bioassay described here utilizes
      a sub clone of the murine 32D cell line transfected with the gene encoding for
      the human erythopoietin (HuEPO) receptor. Erythropoietin (EPO), EP1 and EP2 exert
      their proliferative effect on the cell line by signaling through the HuEPO
      receptor. The proliferation induced by the erythropoietic proteins was measured
      by [methyl-(3)H]thymidine incorporation into the cellular DNA. The assay was
      conducted in 96-well microtiter plates and had relatively high throughput. The
      Guidelines of the International Conference on Harmonization (ICH) were followed
      for the validation of the different assay parameters including robustness,
      linearity, accuracy, precision, limit of quantitation (LOQ) and specificity. The
      robustness of the bioassay is demonstrated by the lack of an effect of age of the
      32D cell culture on the performance of the EP2 bioassay. The bioassay
      demonstrated good linearity, yielding a coefficient of determination of 0.99 or
      higher for both EP1 and EP2. The assay showed reproducible dose-response curves
      for EP1 in the range of 0.039-2.5 ng/mL and for EP2 in the range of 0.125-8
      ng/mL. The accuracy estimates ranged between 98% and 108% for EP1 and between 90%
      and 110% for EP2 in the reproducible range mentioned above. Intermediate
      precision (within-plate R.S.D.) in the same range was within 26% and 17% for the
      EP1 and EP2 bioassays, respectively. The validated bioassays for EP1 and EP2 were
      utilized to quantitatively analyze serum samples from a pharmacokinetic study
      conducted to compare the profiles of the two compounds in Sprague-Dawley rats.

PMID- 16971088
TI  - Piplartine induces inhibition of leukemia cell proliferation triggering both
      apoptosis and necrosis pathways.
AB  - Piplartine {5,6-dihydro-1-[1-oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]
      2(1H)pyridinone} is an alkaloid/amide component of Piper species. The purpose of
      the present study was to examine the antiproliferative effects of piplartine on
      human leukemia cell lines HL-60, K562, Jukart, and Molt-4 using the trypan blue
      exclusion method, as well as the effect of piplartine on DNA synthesis. The
      viability of all human leukemia cell lines were not affected by piplartine after
      6 h, 9 h, and 12 h exposure, whereas a steady decline was seen after an exposure
      time of 24 h. The antiproliferative activity of piplartine seemed to be related
      to the inhibition of DNA synthesis, as revealed by the reduction of 5-bromo-2'
      deoxyuridine (BrdU) incorporation after 24h of incubation. Piplartine-mediated
      reduction in cell number was associated with an increasing number of dead cells
      at a concentration of 10 microg/ml. These findings were corroborated by
      morphologic analysis. However, at the lowest concentration (2.5 microg/ml),
      piplartine-treated cells exhibited typical apoptotic morphological changes. The
      increase in caspase-3 activity was also observed in lysates of piplartine-treated
      cells (2.5 microg/ml). Our findings suggest that piplartine can suppress leukemia
      growth and reduce cell survival, triggering both apoptosis and/or necrosis,
      depending on the concentration used.

PMID- 16971089
TI  - Psychosocial treatment malls for people with intellectual disabilities.
AB  - The provision of active treatment for people with intellectual disabilities has
      been seminal in the literature and in practice for a number of years. Active
      treatment has programmatic, financial, and legal ramifications for agencies and
      should be at the center of all appropriate treatment plans. The current work
      examines the use of psychosocial rehabilitation treatment malls to deliver active
      treatment to people with intellectual disabilities. The history, development, and
      implementation of these methods are discussed, with emphasis on services that are
      functional, meaningful, and portable. The importance of the therapeutic milieu is
      considered in context and discussed as the primary pathway to increased community
      integration. Finally, future directions of the treatment malls are considered.

PMID- 16971090
TI  - Extended LATER model can account for trial-by-trial variability of both pre- and
      post-processes.
AB  - We present a new decision-making model that can account for trial-by-trial
      variability induced by a process ("pre-process") that occurs before an explicit
      sensory signal specifying a later motor response. A process after explicit
      sensory signals, referred to herein as the "post-process", has been investigated
      by a variety of so-called rise-to-threshold models including the LATER model. The
      LATER model formulates post-process variability but treats the pre-process as
      fixed within a block of an experiment. We propose an extension of the LATER
      model, which we call the extended LATER (ELATER) model, to account for trial-by
      trial variability of both pre- and post-processes together. We present the
      mathematical formulation of the ELATER model and analyze its characteristics,
      including numerical examples and an example of saccade latency data in reward
      manipulated conditions with caudate activity. The ELATER model is useful for
      investigating decision making by taking account of trial-by-trial variability of
      both pre- and post-processes.

PMID- 16971091
TI  - Simultaneous bilateral facial palsy as a result of isolated mandibular fractures.
AB  - Post-traumatic bilateral facial nerve palsy is usually associated with fracture
      of the temporal bones in patients who have sustained a significant head injury.
      Facial nerve injury can also very rarely occur because of isolated mandibular
      fractures, without associated temporal bone fractures. Here is reported a case of
      bilateral facial nerve palsy in a patient with mandibular symphysis and bilateral
      condylar fractures of the mandible without evidence of temporal bone fracture or
      significant head injury.

PMID- 16971092
TI  - Substance abuse in first-episode non-affective psychosis.
AB  - Abuse of alcohol and drugs is an important and clinically challenging aspect of
      first-episode psychosis. Only a few studies have been carried out on large-sized
      and reliably characterized samples. These are reviewed, and the results are
      compared with a sample of 300 first-episode psychosis patients recruited for the
      TIPS (Early Treatment and Identification of Psychosis) study from Norway and
      Denmark. Prevalence rates from the literature vary from 6% to 44% for drugs and
      3% to 35% for alcohol. In our sample, 23% abused drugs and 15% abused alcohol
      during the last 6 months. When compared to non-abusers, the drug-abusing group is
      characterized by the following: male gender, younger age, better premorbid
      social, poor premorbid academic functioning, and more contact with friends in the
      last year before onset. Alcohol abusers were the oldest group and they had the
      least contact with friends. A group of patients abusing both drugs and alcohol
      had poor premorbid academic functioning from early childhood. Overall, drug and
      alcohol abuse are highly prevalent in contemporary first-episode psychosis
      samples. In our study, substance abuse comorbidity did not generate differences
      on diagnosis, duration of untreated psychosis, psychiatric symptoms, or global
      functioning at onset/baseline. The premorbid profiles of the substance abusers
      were clearly different from the non-abusers. Drug abusers, in particular, were
      more socially active both premorbidly and during the year preceding the start of
      treatment.

PMID- 16971093
TI  - Colistin as a salvage therapy for nosocomial infections caused by multidrug
      resistant bacteria in the ICU.
AB  - The objective of this study was to determine the efficacy of systemic colistin
      therapy in the treatment of nosocomial infections caused by multidrug-resistant
      Acinetobacter baumannii or Pseudomonas aeruginosa and to study related adverse
      events. We prospectively studied 78 infections caused by multidrug-resistant A.
      baumannii or P. aeruginosa that were treated with colistin. The sites of
      infection were pulmonary infection (78.2%), urinary tract infection (7.7%),
      primary bloodstream infection (11.5%) and meningitis (2.6%). The mean daily dose
      of colistin was 5.5+/-1.1 MU/day (range 2-9 MU/day) and the mean duration of
      colistin therapy was 9.3+/-3.8 days (range 5-21 days). A favourable clinical
      response to colistin occurred in 60 cases (76.9%). Renal failure occurred in only
      seven cases. We conclude that colistin can be a safe and effective salvage
      therapeutic option for nosocomial infections caused by multidrug-resistant A.
      baumannii or P. aeruginosa.

PMID- 16971094
TI  - A simple and efficient method to identify replacements of P-lacZ by P-Gal4 lines
      allows obtaining Gal4 insertions in the bithorax complex of Drosophila.
AB  - The functional replacement of one gene product by another one is a powerful
      method to study specificity in development and evolution. In Drosophila, the
      Gal4/UAS method has been used to analyze in vivo such functional substitutions.
      To this aim, Gal4 lines that inactivate a gene and reproduce its expression
      pattern are required, and they can be frequently obtained by replacing pre
      existing P-lacZ lines with such characteristics. We have devised a new method to
      quickly identify replacements of P-lacZ lines by P-Gal4 lines, and applied it
      successfully to obtain Gal4 insertions in the Ultrabithorax and Abdominal-B Hox
      genes. We have used these lines to study the functional replacement of a Hox gene
      by another one. Our experiments confirm that the abdominal-A gene can replace
      Ultrabithorax in haltere development but that it cannot substitute for Abdominal
      B in the formation of the genitalia.

PMID- 16971095
TI  - Effects of newcastle disease virus glycoproteins on the structural and thermal
      behaviour of 1,2-dihexadecyl-sn-glycero-3-phosphatidylcholine lipid membranes
      under osmotic stress conditions.
AB  - The interaction of hem agglutininneuraminidase (HN) and fusion (F) glycoproteins
      with swollen vesicles of 1,2-dihexadecyl-sn-glycero-3-phosphatidylcholine (DHPC)
      was investigated under transition from gel to fluid phase. X-ray studies of the
      structure of lipid/HN-F mixtures in normal and swollen vesicles have shown that
      the lamellar bilayer structure predominate in the gel and liquid crystalline
      phases. A swollen lipid phase, in which the mean repeat distance of lipid
      bilayers is larger than in the other phases was found. The nature of this phase
      is similar to the anomalous bilayer swelling reported in literature. The presence
      of HN and F in the vesicles led to the coexistence of structures with low and
      high lamellar order, showing larger repeat distance in comparison with the pure
      lipid. This finding was attributed to the increase in the lipid bilayer thickness
      due to the HN-F included in the free water layer. The thermal behaviour of the
      system was not affected by the vesicle swelling. The data showed the existence of
      gel and liquid crystalline lamellar phases and changes in lipid/HN-F specific
      heats, mainly due to the concentration effect of the HN-F and its location in the
      free water layer.

PMID- 16971096
TI  - Polyelectrolyte functionalized magnetic emulsion for specific isolation of
      nucleic acids.
AB  - A magnetic oil in water (o/w) emulsion was cationized by adsorption of
      poly(ethyleneimine) (PEI). In a subsequent step, the cationic particles were
      derivatized with partially hydrolyzed poly(maleic anhydride-alt-methyl vinyl
      ether) copolymer (PMAMVE) to lead negatively charged colloids. The experimental
      conditions for the covalent grafting of the PMAMVE were selected on the basis of
      colloidal stability, charge inversion and absence of inhibition of the enzymatic
      DNA/RNA amplification reactions. Once the experimental conditions were selected,
      oligonucleotides (ODN) bearing particles were obtained according to the
      sequential process: (i) grafting of single stranded ODNs onto PMAMVE; (ii)
      grafting of the PMAMVE-ODN conjugates onto the cationic particles according to
      the conditions defined above. In this strategy, both steps could be independently
      controlled. The ODN-PMAMVE-particles conjugates were very stable with time, did
      not inhibit RT-PCR and were capable of hybridizing specifically with the
      complementary target.

PMID- 16971097
TI  - Development of hollow/porous calcium pectinate beads for floating-pulsatile drug
      delivery.
AB  - The purpose of this work was to develop hollow calcium pectinate beads for
      floating-pulsatile release of diclofenac sodium intended for
      chronopharmacotherapy. Floating pulsatile concept was applied to increase the
      gastric residence of the dosage form having lag phase followed by a burst
      release. To overcome limitations of various approaches for imparting buoyancy,
      hollow/porous beads were prepared by simple process of acid-base reaction during
      ionotropic crosslinking. The floating beads obtained were porous (34% porosity),
      hollow with bulk density<1 and had Ft50% of 14-24 h. In vivo studies by gamma
      scintigraphy determined on rabbits showed gastroretention of beads up to 5 h. The
      floating beads provided expected two-phase release pattern with initial lag time
      during floating in acidic medium followed by rapid pulse release in phosphate
      buffer. This approach suggested the use of hollow calcium pectinate
      microparticles as promising floating-pulsatile drug delivery system for site- and
      time-specific release of drugs acting as per chronotherapy of diseases.

PMID- 16971098
TI  - In vitro erythemal UV-A protection factors of inorganic sunscreens distributed in
      aqueous media using carnauba wax-decyl oleate nanoparticles.
AB  - This paper describes the in vitro photoprotection in the UV-A range, i.e. 320-400
      nm obtained by the use of carnauba wax-decyl oleate nanoparticles either as
      encapsulation systems or as accompanying vehicles for inorganic sunscreens such
      as barium sulfate, strontium carbonate and titanium dioxide. Lipid-free inorganic
      sunscreen nanosuspensions, inorganic sunscreen-free wax-oil nanoparticle
      suspensions and wax-oil nanoparticle suspensions containing inorganic sunscreens
      dispersed either in their oil phase or their aqueous phase were prepared by high
      pressure homogenization. The in vitro erythemal UV-A protection factors (EUV-A
      PFs) of the nanosuspensions were calculated by means of a sun protection
      analyzer. EUV-A PFs being no higher than 4 were obtained by the encapsulation of
      barium sulfate and strontium carbonate, meanwhile by the distribution of titanium
      dioxide in presence of wax-oil nanoparticles, the EUV-A PFs varied between 2 and
      19. The increase in the EUV-A PFs of the titanium dioxide obtained by the use of
      wax-oil nanoparticles demonstrated a better performance of the sun protection
      properties of this pigment in the UV-A region.

PMID- 16971099
TI  - Inhibitory activity against papain, a CA1 cysteine peptidase, in
      Saccharomycetaceae.
AB  - A search for new biological sources of cysteine peptidase inhibitors has not only
      an academic aspect but is of great importance in medicine and biotechnology. The
      activity of CA1 peptidases can be inhibited by proteins of nine structurally
      different families. Although these inhibitors are widespread in nature, there is
      little information on them in yeast and in the kingdom of fungi overall. To gain
      insight into the endogenous inhibitors of CA1 cysteine peptidases in unicellular
      fungi, we initiated a study of the extra- and intracellular antipapain activity
      in yeast. We report here, for the first time, an analysis of the inhibitory
      activity against papain in the culture medium and the cell-free extract of 16
      yeast strains belonging to the Saccharomycetaceae family. The existence of the
      antipapain activity, likely from protein inhibitors, in all the tested yeast
      strains has been demonstrated.

PMID- 16971100
TI  - Isolation and initial characterization of the tellurite reducing moderately
      halophilic bacterium, Salinicoccus sp. strain QW6.
AB  - Among the 49 strains of moderately halophilic bacteria isolated from the salty
      environments of Iran, a Gram-positive coccus designated as strain QW6 showed high
      capacity in the removal of toxic oxyanions of tellurium in a wide range of
      culture medium factors including pH (5.5-10.5), temperature (25-45 degrees C),
      various salts including NaCl, KCl, and Na(2)SO(4) (0.5-4 M), selenooxyanions (2
      10 mM), and at different concentrations of potassium tellurite (0.5-1 mM) under
      aerobic condition. Phenotypic characterization and phylogenetic analyses based on
      16S rDNA sequence comparisons indicated that this strain was a member of the
      genus Salinicoccus. The maximum tellurite removal was exhibited in 1.5M NaCl at
      35 degrees C, while the activity reduced by 53% and 47% at 25 and 45 degrees C,
      respectively. The optimum pH for removal activity was shown to be 7.5, with 90%
      and 83% reduced removal capacities at the two extreme values of 5.5 and 10,
      respectively. The impact of different concentrations of selenooxyanions (2-10 mM)
      on tellurite removal by strain QW6 was evaluated. The ability of strain QW6 in
      the removal of tellurite in the presence of 6mM selenite increased by 25%. The
      concentration of toxic potassium tellurite in the supernatant of the bacterial
      culture medium decreased by 99% (from 0.5 to 0.005 mM) after 6 days and the color
      of the medium changed to black due to the formation of less toxic elemental
      tellurium.

PMID- 16971101
TI  - Comparison of Sybr Green I, ELISA and conventional agarose gel-based PCR in the
      detection of infectious bursal disease virus.
AB  - The current available molecular method to detect infectious bursal disease virus
      (IBDV) is by reverse transcriptase-polymerase chain reaction (RT-PCR). However,
      the conventional PCR is time consuming, prone to error and less sensitive. In
      this study, the performances of Sybr Green I real-time PCR, enzyme-linked
      immunosorbent assay (ELISA) and conventional agarose detection methods in
      detecting specific IBDV PCR products were compared. We found the real-time PCR
      was at least 10 times more sensitive than ELISA detection method with a detection
      limit of 0.25pg. The latter was also at least 10 times more sensitive than
      agarose gel electrophoresis detection method. The developed assay detects both
      very virulent and vaccine strains of IBDV but not other RNA viruses such as
      Newcastle disease virus and infectious bronchitis virus. Hence, Sybr Green I
      based real-time PCR is a highly sensitive assay for the detection of IBDV.

PMID- 16971102
TI  - Diversity and differentiation among fluorescent pseudomonads in crop rhizospheres
      with whole-cell protein profiles.
AB  - Fluorescent pseudomonads from rhizospheres of four different crops, grown under
      similar soil and climatic conditions were phenotypically characterized to
      differentiate them into biovars. In protein electrophenogram studies of
      relationships among fluorescent pseudomonads by UPGMA cluster analysis based on
      DICE similarity index, the isolates were mainly discerned into three major
      clusters representing four different biovars. The biovars generally matched the
      delineated phenotypic clusters with the exception of a strain belonging to biovar
      II. However, the isolates representing similar rhizospheres and geographic
      locations were generally distributed into different phenotypic clusters as
      influenced by factors yet to be determined. The studies reinstated the importance
      of whole-cell protein analyses in characterizing pseudomonads and assessing their
      diversity.

PMID- 16971103
TI  - Attentional distraction reduces the affective but not the sensory dimension of
      perceived dyspnea.
AB  - The perception of dyspnea shows many similarities to the perception of pain. Both
      are multidimensional processes, which are not only influenced by sensory input
      but also by nonsensory factors like attention. Recent research has suggested that
      attentional distraction might reduce the perception of dyspnea but results are
      conflicting. Furthermore, the specific impact of attentional distraction on the
      distinct dimensions of perceived dyspnea has not been studied yet. Therefore, the
      present study examined the specific impact of changes in the attentional focus on
      the sensory and affective dimension of perceived dyspnea. Dyspnea was induced in
      forty-four healthy volunteers (mean age: 27.7 years, range: 18-47 years) by
      breathing through an inspiratory resistive load (3.57 kPa/L/s), while attention
      was directed either to breathing or distracted by reading texts. Inspiratory time
      (T(i)) and breathing frequency (f) were measured continuously. After each
      condition the experienced intensity (i.e., sensory dimension) and unpleasantness
      (i.e., affective dimension) of dyspnea were rated on separate visual analog
      scales (VAS), presented in randomized order. ANOVAs showed that attentional
      distraction during loaded breathing reduced the perceived unpleasantness of
      dyspnea (P<0.05), while the perceived intensity of dyspnea as well as T(i) and f
      remained unchanged. The results show that attentional distraction reduces the
      affective, but not the sensory dimension of induced dyspnea in healthy
      volunteers. Future studies are needed to clarify whether attentional distraction
      can effectively be used as intervention technique for reducing the unpleasant
      aspects of dyspnea in different patients groups.

PMID- 16971104
TI  - Reference equations for spirometry from a general population sample in central
      Italy.
AB  - Aim of this study was to derive new lung function reference equations and compare
      the predicted values with those from three sets of existing reference equations:
      one derived from a Northern Italy population and the two others widely used in
      European (ECCS) and American (NHANES III) clinical practice. Reference equations
      for flow-volume curve indexes and VC were derived on 497 normal subjects, aged 8
      74, from the epidemiological survey in Pisa, Central Italy (1991-1993). By
      applying natural cubic splines, one single smooth and continuous equation for the
      entire age range was provided for each index, separately by gender. Along with
      age and height, reference values also depended on BMI. Differences among the four
      reference equations for FEV(1), FVC, VC were quantified for average subjects. The
      magnitude largely varied over the age range in both genders, reaching up to half
      litre of air volume at specific ages. Age-gender-specific prevalence rates of
      airway obstruction, as defined by the ERS criterion, largely varied by applying
      the considered equations, the differences ranging from -3% to 28%. The observed
      discrepancies confirm that reference equations should be derived from a
      population most similar to that for which the equations are to be used and based
      on measurements obtained by the same instrument and testing procedures, in order
      to minimize technical variability in lung function both for clinical and
      epidemiological purposes.

PMID- 16971106
TI  - The Alchemist's dream resource.

PMID- 16971105
TI  - Pelleted organo-mineral fertilisers from composted pig slurry solids, animal
      wastes and spent mushroom compost for amenity grasslands.
AB  - In Ireland, conversion of biodegradable farm wastes such as pig manure spent
      mushroom compost and poultry litter wastes to pelletised fertilisers is a
      desirable option for farmers. In this paper, results obtained from the composting
      of pig waste solids (20% w/w) blended with other locally available biodegradable
      wastes comprising poultry litter (26% w/w), spent mushroom compost (26% w/w),
      cocoa husks (18% w/w) and moistened shredded paper (10% w/w) are presented. The
      resulting 6-mo old 'mature' composts had a nutrient content of 2.3% total N, 1.6%
      P and 3.1% K, too 'low' for direct use as an agricultural fertiliser.
      Formulations incorporating dried blood or feather meal amendments enriched the
      organic N-content, reduced the moisture in mature compost mixtures and aided the
      granulation process. Inclusion of mineral supplements viz., sulphate of ammonia,
      rock phosphate and sulphate of potash, yielded slow release fertilisers with
      nutrient N:P:K ratios of 10:3:6 and 3:5:10 that were suited for amenity
      grasslands such as golf courses for spring or summer application and autumn
      dressing, respectively. Rigorous microbiological tests carried out throughout the
      composting, processing and pelletising phases indicated that the formulated
      organo-mineral fertilisers were free of vegetative bacterial pathogens.

PMID- 16971107
TI  - Preparation of polyaniline-modified electrodes containing sulfonated
      polyelectrolytes using layer-by-layer techniques.
AB  - Polyaniline (PAni) has been used frequently for the construction of biosensors.
      However, a prime limitation is its instability at basic or neutral pH because of
      the loss of its electrochemical activity and conductivity. In this study, three
      available sulfonated polyanions: Nafion, poly(vinyl sulfonate) (PVS), and
      poly(styrene sulfonate) (PSS) serving as the counterion and providing an acidic
      microenvironment to stabilize PAni, are used to fabricate a sensor for ammonium
      ion detection. Nafion used to be a common ion-sensitive membrane due to its high
      proton conductivity. However, its high cost and limited solubility has
      constrained its uses. PVS and PSS are water-soluble polymers, easily
      incorporating with PAni to form the composites. Surface analysis by electron
      spectroscopy for chemical analysis (ESCA) and scanning electron microscope (SEM),
      and the electrochromic property for the PAni composites provided the convenient
      tools to characterize the electrode fabrication. On the aspect of sensing the
      ammonium ions, the modified electrodes exhibited electroactivity of PAni in
      ammonium ion detection and also showed the linear dependence of reduction current
      on the ammonium ion concentration. The pH effect on the sensing response was also
      evaluated and found insignificant to the response (ranging from pH 6.9-7.6). For
      increasing the stability of the electrodes, the diazo-resin (DAR) was introduced
      to the coat on the outmost layer and then cured by UV irradiation, giving the
      covalent network between the layers of polyelectrolytes. The PSS-doped PAni
      electrode was found to perform detection sensitivity in the linear range of 0
      100mM of ammonium ion concentration.

PMID- 16971108
TI  - Spreeta-based biosensor assays for endocrine disruptors.
AB  - The construction and performance of an automated low-cost Spreeta-based prototype
      biosensor system for the detection of endocrine disrupting chemicals (EDCs) is
      described. The system consists primarily of a Spreeta miniature liquid sensor
      incorporated into an aluminum flow cell holder, dedicated to support a Biacore
      chip frame, in combination with a simple pressurized air-driven fluid system.
      During the optimization, a monoclonal antibody (MAb)-based immunoassay for the
      estrogenic compound bisphenol A (BPA) was used as a model. After the optimization
      two thyroxine transport protein inhibition assays for thyroid endocrine
      disruptors were implemented. The average noise of the system for 1 min of
      baseline was 1.1 microRIU (refractive index units) and it could be operated in
      the range of 18-22 degrees C with a minimum baseline drift (5-10 microRIU/100
      min). Optimum signal to noise ratio (S/N R) was obtained using a flow cell height
      of 100 microm and a flow rate of 180 microl/min. The sensitivity of the Spreeta
      based biosensor inhibition assays implemented (50% inhibition concentration
      (IC50) of 30.2 nM for BPA using MAb12 and 12.3 and 11.6 nM for thyroxine (T4)
      using thyroxine-binding globulin (TBG) and recombinant transthyretin (rTTR),
      respectively) was comparable to the sensitivity previously obtained using a
      Biacore 3000 (IC50 of 39.9 nM for BPA and 8.6 and 13.7 nM, respectively, for T4).
      The results indicate that the alternative prototype system can be used in
      combination with ready-to-use biosensor chip surfaces and it is potentially a
      useful tool for the bioeffect-related screening of EDCs.

PMID- 16971109
TI  - Flow analysis coupled with PQC/DNA biosensor for assay of E. coli based on
      detecting DNA products from PCR amplification.
AB  - A flow-through PQC/DNA biosensor system is developed by combining sequential flow
      polymerase chain reaction (PCR) products denaturing prior to piezoelectric quartz
      crystal (PQC) detection via hybridization of ssDNA. The PQC/DNA biosensor is
      fabricated based on complex formation of neutravidin/biotinylated probe in 0.2M
      NaCl in TE buffer (10mM Tris, 1mM EDTA, pH 7.5). Results show that the coating
      fabricated provides a desirable quality with satisfactory performance. Its
      application for Escherichia coli detection under controlled flow at 0.02 mL/min
      for denaturing PCR products and 10 mL/min for transferring solution between
      reactors and delivering samples to detector to reduce rehybridization leads to
      significant improvement in repeatability (R.S.D.<6%, n=5) and sensitivity
      (DeltaF=34 Hz/1000 E. coli cells) as compared to existing manual method
      (R.S.D.=19%, n=5 and DeltaF=26 Hz/1000 E. coli cells, respectively). Down to 23
      E. coli cells are detected, satisfying the HKEPD requirements for E. coli count
      in beach water.

PMID- 16971110
TI  - Ag/SiO2 core-shell nanoparticle-based surface-enhanced Raman probes for
      immunoassay of cancer marker using silica-coated magnetic nanoparticles as
      separation tools.
AB  - A simple, sensitive and highly specific immunoassay has been developed based on
      surface-enhanced Raman scattering for human alpha-fetoprotein (AFP), a tumor
      marker for the diagnosis of hepatocellular carcinoma. This strategy combines the
      Ag/SiO2 core-shell nanoparticles embedded with rhodamine B isothiocyanate dye
      molecules as Raman tags and the amino group modified silica-coated magnetic
      nanoparticle as immobilization matrix and separation tool. In the proposed
      system, a sandwich-type immunoassay was performed between polyclonal antibody
      functionalized Ag/SiO2 nanoparticle-based Raman tags and monoclonal antibody
      modified silica-coated magnetic nanoparticles. The presence of the analyte and
      the reaction between the antigen and antibody can be monitored by the Raman
      spectra of the Ag/SiO2 tags. Compared to the previous surface-enhanced Raman
      immunoassays, the main advantage of this strategy lies in two aspects. One is the
      high stability of Raman tags derived from the silica shell-coated silver core
      shell nanostructure. The other is the use of silica-coated magnetic nanoparticles
      as immobilization matrix and separation tool, thus avoiding complicated
      pretreatment and washing steps. We have studied in detail the experimental
      parameters such as the effects of the antibody concentration modified on the
      Raman tags and on the magnetic particles, and the immunoreaction time. Using this
      strategy, concentration of human AFP up to 0.12 microg/ml was detected with a
      detection limit of 11.5 pg/ml.

PMID- 16971111
TI  - Microstructured extracellular matrices in tissue engineering and development.
AB  - Microscale heterogeneity in the extracellular matrix (ECM) provides spatial
      information that allows tissues to develop and function properly in vivo. This
      heterogeneity in composition (chemistry) and structure (geometry) creates
      distinct microenvironments for the cells that comprise a tissue. In response,
      populations of cells can coordinate their behaviors across micrometer-to
      millimeter length scales to function as a unified whole. We believe techniques to
      mimic the microscale heterogeneity of the ECM in vitro will revolutionize studies
      that examine how large groups of cells interact. Micropatterned ECMs used for
      engineering perfused microvascular networks and functional epidermis and for
      understanding symmetry-breaking events in epithelial morphogenesis illustrate
      potential applications in tissue engineering and development.

PMID- 16971112
TI  - Imaging spatiotemporal dynamics of neuronal signaling using fluorescence
      resonance energy transfer and fluorescence lifetime imaging microscopy.
AB  - The spatiotemporal localization of neuronal signaling is important for triggering
      neuronal responses in specific locations at precise times. Fluorescence resonance
      energy transfer imaging enables measurement of spatiotemporal dynamics of
      signaling activity in live neurons. Although the usefulness of fluorescence
      resonance energy transfer is well recognized, there are many difficulties in
      applying it, particularly when imaging in neuronal micro-compartments in light
      scattering brain tissue. Fluorescence resonance energy transfer has been imaged
      using several techniques including intensity-based methods, fluorescence lifetime
      imaging and fluorescence anisotropy imaging. These methods have different
      advantages and disadvantages, and thus are suitable in different applications.

PMID- 16971113
TI  - Directing neuron-specific transgene expression in the mouse CNS.
AB  - Recent advances in molecular genetics have produced many novel strategies for
      directing the expression of both functional and regulatory elements in transgenic
      mice. With the application of such approaches, the specific populations that
      comprise CNS networks can be both visualized and manipulated. Transgenic methods
      now range from the use of specific enhancer elements and large genomic regions
      assembled using BACs and PACs, to the use of gene targeting to a specific locus.
      In addition, the advent of transactivators and site-specific recombinases has
      provided unprecedented spatial and temporal control for directing expression in
      the CNS using a combination of appropriate alleles. As a result, the promise of
      being able to use transgenics to target specific neuronal populations is now
      being realized.

PMID- 16971114
TI  - Decoding sugar functions by identifying target glycoproteins.
AB  - Identification of the glycosyltransferase genes that are involved in the
      biosynthesis of glycoconjugates has opened up new avenues in glycobiology, the
      decoding of the function of sugar chains. Specific biosynthesis of branched N
      glycan structures by glycosyltransferases functionally modifies target
      glycoproteins, as observed in the recognition of cancer cells. A mouse model with
      a specific defect in alpha1-6 fucosylation showed emphysema-like changes of the
      lung and severe degradation of lung alveoli that derived from the dysregulation
      of signaling through the transforming growth factor-beta receptor. Functional
      glycomics and the identification of target proteins will provide a new way to
      elucidate the nature of disease in the post-genomic era.

PMID- 16971115
TI  - What is the significance of pT0 at cystectomy?
AB  - The current treatment for muscle invasive bladder cancer is radical cystectomy.
      However, this approach leads to significant changes in the patient's quality of
      life, as well as potential treatment failure. And so, with the introduction of
      alternative and neoadjuvant therapies available, the presence of pT0 tumour at
      cystectomy confers a number of issues. The variability in numbers of pT0 tumours
      at cystectomy highlights the importance of adequate clinical staging, as well as
      the increasing successful use of neoadjuvant chemotherapy. Although current
      literature is limited, patients with prior clinical stage of muscle-invasive but
      node-negative disease are likely to demonstrate the most improvement in
      survivability if they subsequently develop pT0 at cystectomy. This review also
      highlights the importance of response to chemotherapy as an indicator of
      subsequent prognosis. With increasing numbers of pT0 tumours seen at radical
      cystectomy, it is suggested that more conservative measures, such as re-staging
      following neoadjuvant chemotherapy and even 'selective bladder preservation'
      treatment, may be the future for the management of muscle invasive bladder
      cancer.

PMID- 16971116
TI  - Odorless benzenethiols in synthesis of thioglycosides and its application for
      glycosylation reactions.
AB  - p-Octyloxybenzenethiol (2) was synthesized as a new odorless benzenethiol.
      Moreover, preparation of thioglycosides using 2 and their application for
      glycosylation reactions were attempted. As a result, it was found that the
      thioglycosides were as excellent glycosyl donors as 4-dodecylphenyl 1-thio
      glycosides, which were previously reported by our group, and more useful than the
      previous donors in terms of fine chemistry in glycosylation reaction activated
      with silver triflate and N-iodosuccinimide (NIS). In addition, this method was
      applicable to the sialylation with NIS and triflic acid. All procedures from the
      preparation of thioglycosides to the glycosylation reaction could be attained
      completely under conditions where no malodor was generated.

PMID- 16971117
TI  - Identification of non-furan containing A2A antagonists using database mining and
      molecular similarity approaches.
AB  - Database searching led to the identification of potent A(2A) antagonists which do
      not contain the privileged furan moiety and which show selectivity over A(1)
      receptors. Simple substructure searching on a proprietary database identified
      compounds with activities in the low nM range. A targeted approach to the
      identification of non-furan containing compounds resulted in the identification
      of two novel series, with potency, selectivity and directional SAR from screening
      113 compounds.

PMID- 16971118
TI  - A protein kinase signal-responsive gene carrier modified RGD peptide.
AB  - We have previously reported artificial gene-regulation systems responding to
      cyclic AMP-dependent protein kinase (PKA) using a cationic polymer. However, this
      polymer alone cannot deliver any gene into living cells. In the present work, we
      modified the signal-responsive polymer to the RGD peptide for the introduction of
      a polymer/DNA complex into living cells and succeeded in regulating the gene
      expression responding to intracellular PKA activation.

PMID- 16971119
TI  - Identification and optimisation of 5-amino-7-aryldihydro-1,4-diazepines as 5-HT2A
      ligands.
AB  - A several series of low molecular weight 5-HT(2A) leads were identified from an
      analysis of HTS data, the exploration of SAR and optimization of one series using
      parallel synthesis are described, affording compound 22 (5-HT(2A) IC(50) 1.1 nM).

PMID- 16971120
TI  - Aminopyridine carboxamides as c-Jun N-terminal kinase inhibitors: targeting the
      gatekeeper residue and beyond.
AB  - The structure-activity relationships of 5,6-positions of aminopyridine
      carboxamide-based c-Jun N-terminal Kinase (JNK) inhibitors were explored to
      expand interaction with the kinase specificity and ribose-binding pockets. The
      syntheses of analogues and the impact of structural modification on in vitro
      potency and cellular activity are described.

PMID- 16971121
TI  - Exploration of the diketoacid integrase inhibitor chemotype leading to the
      discovery of the anilide-ketoacids chemotype.
AB  - Integrase is one of three enzymes expressed by HIV and represents a validated
      target for therapy. A previous study of the diketoacid-based chemotype suggested
      that there are two aryl-binding domains on integrase. In this study,
      modifications to the indole-based diketoacid chemotype are explored. It is
      demonstrated that the indole group can be replaced with secondary but not
      tertiary (e.g., N-methyl) aniline-based amides without sacrificing in vitro
      inhibitory activity. The difference in activity between the secondary and
      tertiary amides is most likely due to the opposite conformational preferences of
      the amide bonds, s-trans for the secondary-amide and s-cis for the tertiary
      amide. However, it was found that the conformational preference of the tertiary
      amide can be reversed by incorporating the amide nitrogen atom into an indoline
      heterocycle, resulting in very potent integrase inhibitors.

PMID- 16971122
TI  - Inhibitors of unactivated p38 MAP kinase.
AB  - Inhibition of the p38 map kinase pathway has been shown to be beneficial in the
      treatment of inflammatory diseases. The first class of potent p38 kinase
      inhibitors was the pyridinylimidazole compounds from SKB. Since then several
      pyridinylimidazole-based compounds have been shown to inhibit activated p38
      kinase in vitro and in vivo. We have developed a novel series of
      pyridinylimidazole-based compounds, which potently inhibit the p38 pathway by
      binding to unactivated p38 kinase and only weakly inhibiting activated p38 kinase
      activity in vitro.

PMID- 16971123
TI  - Microwave expedited synthesis of 5-aminocamptothecin analogs: Inhibitors of
      hypoxia inducible factor HIF-1alpha.
AB  - A series of 5-aminosubstituted camptothecin analogs were prepared from the
      corresponding 5-hydroxycamptothecin using microwave irradiation. The analogs were
      assayed for ability to inhibit the action of hypoxia inducible factors (HIF
      1alpha and HIF-2alpha). The 5-fluoroethyl analog showed potent inhibitory
      activity and is now the focus of ongoing pathway analysis and potential as an
      antiproliferative agent.

PMID- 16971124
TI  - Distachyasin: A new antioxidant metabolite from the leaves of Carex distachya.
AB  - A novel antioxidant prenylated stilbenoid, distachyasin, has been isolated from
      the leaves of Carex distachya. Its structure has been elucidated on the basis of
      the spectroscopic characteristics. Bidimensional NMR, and crystallographic data
      and computational calculations have furnished important data useful for the
      characterization and the stereochemistry of the molecule. The compound has a
      tetracyclic skeleton derived from carexane. The compound has been assayed, for
      the antioxidant activity, by measuring its capacity to scavenge the H(2)O(2),
      nitric oxide, superoxide radical and to inhibit formation of TBARS
      (thiobarbituric acid reactive species).

PMID- 16971125
TI  - Nurses' roles with families: perceptions of ICU nurses.
AB  - This descriptive survey examined: (a) differences between nurses' (N=47)
      perceptions of self-performance and that of their colleagues with regard to their
      roles with family members of intensive care patients, and (b) the impact of
      nurses' comfort on their role enactment as it relates to family focused
      interventions. Participants rated their self-performance higher than that of
      their colleagues with respect to 15 of the 19 items, suggesting that they think
      they perform better than their colleagues. The results also showed that nurses'
      comfort was positively correlated with their role enactment as it pertains to
      discussing patient prognosis (r=.496; p<.001), explaining patient's equipment
      (r=.43; p=.003), and discussing the possibility of death with family members
      (r=.43; p=.003).

PMID- 16971126
TI  - Synthesis of 4-aryl-3,4-dihydropyrimidin-2(1H)-thione derivatives as potential
      calcium channel blockers.
AB  - Biginelli reaction which involves condensation of methyl 3-oxopentanoate,
      aromatic aldehydes and thiourea with a catalytic amount of HCl at reflux
      temperature has been used for the synthesis of 4-aryl-6-ethyl-5-(methoxycarbonyl)
      3,4-dihydropyrimidin-2(1H)-thiones (1-16). In addition, Lewis acids such as
      FeCl(3).6H(2)O and/or H(3)BO(3) were also used as catalysts for one-pot synthesis
      of the products. Compared to the classical Biginelli reaction conditions, the
      usage of Lewis acids has the advantage of good yields and short reaction times.
      The calcium channel blocker activities of 1-16 were screened by the tests
      performed on isolated rat ileum and thoracic aorta. Although product 11, 2
      nitrophenyl-derivative, has potent antispasmodic activity on BaCl(2)-stimulated
      rat ileum, it does not have vasodilator activity on KCl-stimulated rat thoracic
      aorta. Product 15, 2-ethoxyphenyl-derivative, exhibited significant antispasmodic
      and vasodilator activities in both screening paradigms.

PMID- 16971127
TI  - Phenolics and antimicrobial activity of traditional stoned table olives
      'alcaparra'.
AB  - In the present work, we report the determination of phenolic compounds in
      'alcaparra' table olives by reversed-phase HPLC/DAD, and the evaluation of their
      extract in vitro activity against several microorganisms that may be causal
      agents of human intestinal and respiratory tract infections, namely Gram positive
      (Bacillus cereus, Bacillus subtilis, and Staphylococcus aureus), Gram negative
      bacteria (Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae)
      and fungi (Candida albicans and Cryptococcus neoformans). Three flavonoidic
      compounds were identified and quantified: luteolin 7-O-glucoside, apigenin 7-O
      glucoside, and luteolin. At low concentrations (0.05mg/mL) 'alcaparra' extract
      revealed significant inhibition of both Gram positive and Gram negative bacteria
      growth, with exception of P. aeruginosa. Nevertheless, no antifungal activity was
      observed at the tested concentrations.

PMID- 16971128
TI  - An efficient synthesis and biological activity of substituted p-benzoquinones.
AB  - An efficient synthesis of 2,5-diarylamino-3,6-dichloro-1,4-benzoquinone
      derivatives has been achieved by condensing mono substituted anilines with
      tetrachloro-p-benzoquinone in presence of fused sodium acetate as condensing
      agent under microwave irradiation without any solvent. All the synthesized
      compounds were tested for their antibacterial and antitumour activity using
      standard drugs.

PMID- 16971129
TI  - Exploring the limits of benzimidazole DNA-binding oligomers for the hypoxia
      inducible factor (HIF) site.
AB  - The vascular endothelial growth factor (VEGF) and its receptors have been
      implicated as key-factors in tumor angiogenesis and are major targets in cancer
      therapy. New oligomers which mimic the architecture of DNA-binding polyamides
      have been designed to target the hypoxia inducible factor (HIF-1alpha) binding
      site on the promoter of VEGF gene. These oligomers incorporate an increasing
      number of six-five fused rings such as hydroxybenzimidazole-imidazole,
      benzimidazole-pyrrole, benzimidazole-chlorothiophene, and imidazopyridine
      pyrrole, and bind the VEGF hypoxia response element (HRE) 5'-TACGT-3' with high
      affinity and selectivity.

PMID- 16971130
TI  - Structure-activity studies of cyclic ketone inhibitors of the serine protease
      plasmin: design, synthesis, and biological activity.
AB  - Three series of cyclic ketone inhibitors were synthesized and evaluated against
      the serine protease plasmin. Peptide inhibitors that incorporated 3
      oxotetrahydrofuran and 3-oxotetrahydrothiophene 1,1-dioxide groups had the
      highest activities. Alkylamino substituents, which were designed to bind in the
      S1 subsite of plasmin, were attached to the inhibitors. Compounds 5c and 5g,
      which incorporated 6-aminohexyl substituents, were found to be optimal and
      demonstrated IC(50) values in the low micromolar range. Incorporating
      conformationally constrained peptide segments into the inhibitors did not improve
      their activities.

PMID- 16971131
TI  - Synthesis of three classes of rhodacyanine dyes and evaluation of their in vitro
      and in vivo antimalarial activity.
AB  - Selected members of three classes of rhodacyanine dyes, [0,0]-, [1,0]-, and
      [0,0,0]-rhodacyanines, were synthesized and their in vitro antimalarial
      activities against Plasmodium falciparum K1 (chloroquine-resistant strain) as
      well as their in vivo activities against P. berghei in mice were determined. The
      novel [0,0,0]-rhodacynines, 3e and 3h, possessing a benzothiazole moiety, were
      shown to have highly promising antimalarial activities in vivo. Moreover, the
      [0,0,0]-rhodacyanines were found to be orally bioavailable.

PMID- 16971132
TI  - Synthesis, dihydrofolate reductase inhibition, antitumor testing, and molecular
      modeling study of some new 4(3H)-quinazolinone analogs.
AB  - In order to produce potent new leads for anticancer drugs, a new series of
      quinazoline analogs was designed to resemble methotrexate (MTX, 1) structure
      features and fitted with functional groups believed to enhance inhibition of
      mammalian DHFR activity. Molecular modeling studies were used to assess the fit
      of these compounds within the active site of human DHFR. The synthesized
      compounds were evaluated for their ability to inhibit mammalian DHFR in vitro and
      for their antitumor activity in a standard in vitro tissue culture assay panel.
      Compounds 28, 30, and 31 were the most active DHFR inhibitors with IC(50) values
      of 0.5, 0.4, and 0.4microM, respectively. The most active antitumor agents in
      this study were compounds 19, 31, 41, and 47 with median growth inhibitory
      concentrations (GI(50)) of 20.1, 23.5, 26.7, and 9.1microM, respectively. Of this
      series of compounds, only compound 31 combined antitumor potency with potent DHFR
      inhibition; the other active antitumor compounds (19, 41, and 47) all had DHFR
      IC(50) values above 15microM, suggesting that they might exert their antitumor
      potency through some other mode of action. Alternatively, the compounds could
      differ significantly in uptake or concentration within mammalian cells.

PMID- 16971133
TI  - Inflammatory aneurysm of the ascending aorta.
AB  - Inflammatory aneurysms of the aorta are usually seen in the infrarenal abdominal
      aorta and very rarely in the ascending aorta. We present the case of a 76-year
      old male with inflammatory aneurysm of the ascending aorta.

PMID- 16971134
TI  - ESTS guidelines for intraoperative lymph node staging in non-small cell lung
      cancer.
AB  - The European Society of Thoracic Surgeons (ESTS) organized a workshop dealing
      with lymph node staging in non-small cell lung cancer. The objective of this
      workshop was to develop guidelines for definitions and the surgical procedures of
      intraoperative lymph node staging, and the pathologic evaluation of resected
      lymph nodes in patients with non-small cell lung cancer (NSCLC). Relevant peer
      reviewed publications on the subjects, the experience of the participants, and
      the opinion of the ESTS members contributing on line, were used to reach a
      consensus. Systematic nodal dissection is recommended in all cases to ensure
      complete resection. Lobe-specific systematic nodal dissection is acceptable for
      peripheral squamous T1 tumors, if hilar and interlobar nodes are negative on
      frozen section studies; it implies removal of, at least, three hilar and
      interlobar nodes and three mediastinal nodes from three stations in which the
      subcarinal is always included. Selected lymph node biopsies and sampling are
      justified to prove nodal involvement when resection is not possible. Pathologic
      evaluation includes all lymph nodes resected separately and those remaining in
      the lung specimen. Sections are done at the site of gross abnormalities. If
      macroscopic inspection does not detect any abnormal site, 2-mm slices of the
      nodes in the longitudinal plane are recommended. Routine search for
      micrometastases or isolated tumor cells in hematoxylin-eosin negative nodes would
      be desirable. Randomized controlled trials to evaluate adjuvant therapies for
      patients with these conditions are recommended. The adherence to these guidelines
      will standardize the intraoperative lymph node staging and pathologic evaluation,
      and improve pathologic staging, which will help decide on the best adjuvant
      therapy.

PMID- 16971135
TI  - Successful treatment with one-way endobronchial valve of large air-leakage
      complicating narrow-bore enteral feeding tube malposition.
AB  - Tracheopulmonary intubation is the most common misplacement site for narrow-bore
      feeding tube and it might be associated with severe pleuro-pulmonary
      complications. A 38-year-old female with a severe bilateral pneumonia and acute
      respiratory insufficiency was admitted in the ICU, intubated, and mechanically
      ventilated. Few hours after the insertion of a narrow-bore feeding tube the
      patient's oxygen saturation dropped with hypotension and tachycardia. A large
      left-side hydropneumothorax developed requiring a chest tube. Air-leakage was
      important and bronchoscopic implant of one-way endobronchial valve was
      accomplished. Immediate and substantial decrease of air-leakage was observed, and
      it completely stopped after 5 days; as soon as the patient was extubated.
      Endobrochial one-way valve, specifically designed for bronchoscopic lung volume
      reduction, resulted in being safe and effective to control a significant and
      prolonged air-leakage due to a malposition of a narrow-bore feeding tube.

PMID- 16971136
TI  - Changes in hepatic immunoregulatory cytokines in patients with metastatic
      colorectal carcinoma: implications for hepatic anti-tumour immunity.
AB  - The hepatic immunological environment, dominated by NK and NKR(+) T cells, seems
      specialised to respond to malignant challenge. Ineffective immune responses to
      malignancy are likely determined by factors including alterations in the local
      cytokine profile. This study examines the cytokine milieu of normal and tumour
      bearing liver, quantifying pro-/anti-inflammatory cytokines using modified ELISAs
      and real-time quantitative PCR. Cytokine protein was localised using
      immunohistochemistry. We demonstrate an active cytokine environment in normal
      liver, with high levels of inflammatory and regulatory cytokines. Inflammatory
      IFN-gamma was increased in tumour-bearing liver (p<0.0001). However, a much
      greater increase in anti-inflammatory IL-10, produced by non-parenchymal cells
      (p<0.0005), resulted in a reduced IFN-gamma:IL-10 ratio in tumour-bearing liver
      (p<0.02). In contrast, immunosuppressive TGF-beta and IL-13 were significantly
      downregulated (p<0.02). Furthermore, IL-2 was not increased and IL-15 was reduced
      (p<0.02). The IFN-gamma inducing cytokine, IL-18 was increased in tumour-bearing
      liver (p<0.02), while pro-inflammatory TNF-alpha was suppressed (p<0.05). These
      results suggest that, whilst there is a significant inflammatory immune response
      in tumour-bearing liver, evidenced by increased levels of IFN-gamma,
      disproportionate increase in IL-10 may be a key factor in facilitating tumour
      progression. Therapies aimed at antagonising IL-10-mediated immunosuppression may
      prove a useful strategy in the future treatment of metastatic disease.

PMID- 16971137
TI  - The uncoupling protein 2 modulates the cytokine balance in innate immunity.
AB  - The uncoupling protein 2 (UCP2) is located in the inner mitochondrial membrane
      and downregulates the production of reactive oxygen species (ROS). Recent data
      suggested a role for UCP2 in the immune response. We analyzed further this
      hypothesis during acute Listeria monocytogenes infection in mice. Death of
      infected Ucp2(-/-) mice was delayed in comparison with Ucp2(+/+), suggesting a
      role of UCP2 in the early step of the immune response. In vitro, the higher
      resistance of Ucp2(-/-) mice was not associated with a better control of
      bacterial growth by macrophages. In vivo, a significant increase of recruited
      phagocytes was observed in the spleen of Ucp2(-/-) mice. This was associated with
      a higher level of ROS in the spleen. Upregulation of pro-inflammatory cytokines
      IFNgamma, IL6, and IL1beta and of the chemokine MCP1 was observed in Ucp2(-/-)
      mice 4 days after infection, preceded by a decrease of the anti-inflammatory
      cytokine IL10 production. Present data highlight that, in an acute model of
      infection, UCP2 modulates innate immunity, via the modulation of ROS production,
      cytokine and chemokine production and consequently phagocyte recruitment.

PMID- 16971138
TI  - Preconditioning effects of peroxynitrite in the rat lung.
AB  - Ischaemic preconditioning of the lung leads to a protective effect against
      ischaemia-reperfusion injury, but the underlying mechanisms of this protection
      are not well documented in the lung. The aim of this study was to investigate the
      role of endogenous and exogenous peroxynitrite (ONOO(-)) in preconditioning of
      isolated rat lungs. Lungs, obtained from male rats, were mounted on a perfusion
      apparatus, perfused by Krebs-Henseleit solution at the rate of 0.03mlg(-1)min(-1)
      and inflated with room air. Pulmonary perfusion pressure was measured by a
      pressure transducer and recorded continuously on a computer by using data
      acquisition system. Lungs were preconditioned for 5min by either ischaemia or
      ONOO(-) administration at 10microM, which were followed by 5min reperfusion and
      2h of ischaemia and 10min reperfusion. Two hours of ischaemia without
      preconditioning depressed potassium chloride (KCl)-and phenylephrine
      hydrochloride (PE)-induced responses. Pretreatment of the lungs with ONOO(-)
      scavenger, uric acid (1mM), or poly ADP-ribose synthase inhibitors, 3
      aminobenzamid (3-AB, 1mM) or nicotinamide (1mM), reversed the effects ischaemia
      and ONOO(-)-induced preconditioning and decreased KCl- and PE-induced increases
      in perfusion pressures. Wet/dry weight ratio was markedly reduced in ischaemia
      and ONOO(-)-induced preconditioning groups indicating that preconditioning
      prevents lung oedema. Lung malondialdehyde (MDA) levels were significantly
      depressed in ischaemic and ONOO(-) preconditioning groups. These results suggest
      that ONOO(-) is able to precondition the isolated rat lung and plays a
      significant role in the protective effects of preconditioning.

PMID- 16971139
TI  - alpha-Tocopherol supplementation restores the reduction of erythrocyte glucose-6
      phosphate dehydrogenase activity induced by forced training.
AB  - BACKGROUND: Erythrocyte glucose-6-phosphate dehydrogenase (G6PD) activity is
      closely related to free radical production. alpha-Tocopherol (alpha-T) is
      implicated with the reduction of lipid peroxidation. AIM: To investigate the
      effect of training and alpha-T supplementation on the erythrocyte G6PD activity.
      METHODS: Blood was obtained from 10 basketball players pre-game (group A), post
      game (group B) and after 30 days on alpha-T (dl-alpha-tocopheryl-acetate, 200mg
      24h(-1) orally) supplementation pre- (group C) and post-training (group D). alpha
      T and catecholamines were evaluated with HPLC methods and creatine kinase,
      lactate dehydrogenase, total antioxidant status (TAS) and G6PD activity with
      commercial kits. RESULTS: TAS was increased in the groups with alpha-T addition
      (groups C and D). Post-exercise, TAS and G6PD activity were remarkably higher
      (2.10+/-0.13mmoll(-1), 7.92+/-1.5Ug(-1)Hb, respectively) in group D than those in
      group B (0.92+/-0.10mmoll(-1), 4.8+/-1.4Ug(-1)Hb, p<0.01, respectively). G6PD
      activity positively correlated with TAS (r=0.64, p<0.001) in all the studied
      groups. CONCLUSIONS: Supplementation with alpha-T may protect G6PD activity from
      reduction induced by forced training.

PMID- 16971140
TI  - Bayesian estimation of cerebral perfusion using a physiological model of
      microvasculature.
AB  - Perfusion weighted MRI has proven very useful for deriving hemodynamic parameters
      such as CBF, CBV and MTT. These quantities are important diagnostically, e.g. in
      acute stroke, where they are used to delineate ischemic regions. Yet the standard
      method for estimating CBF based on singular value decomposition (SVD) has been
      demonstrated to underestimate (especially high) flow components and to be
      sensitive to delays in the arterial input function (AIF). Furthermore, the
      estimated residue functions often oscillate. This compromises their physiological
      interpretation/basis and makes estimation of related measures such as flow
      heterogeneity difficult. In this study, we estimate perfusion parameters based on
      a vascular model (VM) which represents heterogeneous capillary flow and
      explicitly leads to monotonically decreasing residue functions. We use a fully
      Bayesian approach to obtain posterior probability distributions for all
      parameters. In simulation studies, we show that the VM method has less bias in
      CBF estimates than the SVD based method for realistic SNRs. This also applies to
      cases where the AIF is delayed. We employ our method to estimate perfusion maps
      using data from (i) a healthy volunteer and (ii) from a stroke patient.

PMID- 16971141
TI  - Molecular taxonomy in the dark: evolutionary history, phylogeography, and
      diversity of cave crayfish in the subgenus Aviticambarus, genus Cambarus.
AB  - Freshwater crayfish species in the subgenus Aviticambarus (Cambaridae: Cambarus)
      are restricted to caves along the Cumberland Plateau, the Sequatchie Valley, and
      the Highland Rim which extend along the Tennessee River in southcentral Tennessee
      and northern Alabama. Historically, three stygobitic species, Cambarus jonesi,
      Cambarus hamulatus, and Cambarus veitchorum, comprise this subgenus. We examine
      species' boundaries and phylogeographic structure of this imperiled Southern
      Appalachian assemblage to shed light on patterns of cave colonization. We also
      provide estimates of genetic diversity for conservation status assessment. Using
      geologic evidence, phylogeographic analyses, and sequence data from five gene
      regions (two nuclear: Histone H3 and GAPDH and three mitochondrial: 12S, 16S, and
      CO1 totaling almost 2700 base pairs), we identify two well-supported cryptic
      species in addition to the three currently recognized taxa. Four of these taxa
      exhibit low levels of genetic variation both currently and historically, which
      may indicate local extirpation events associated with geological and river basin
      changes. Our results also support other recent findings that pre-Pleistocene
      paleodrainages may best explain the current patterns of aquatic faunal
      biodiversity in the Southern Appalachians.

PMID- 16971143
TI  - Phylogenetic relationships of click beetles (Coleoptera: Elateridae) inferred
      from 28S ribosomal DNA: insights into the evolution of bioluminescence in
      Elateridae.
AB  - Although the taxonomy of click beetles (family Elateridae) has been studied
      extensively, inconsistencies remain. We examine here the relationships between
      species of Elateridae based on partial sequences of nuclear 28S ribosomal DNA.
      Specimens were collected primarily from Japan, while luminous click beetles were
      also sampled from Central and South America to investigate the origins of
      bioluminescence in Elateridae. Neighbor-joining, maximum-parsimony, and maximum
      likelihood analyses produced a consistent basal topology with high statistical
      support that is partially congruent with the results of previous investigations
      based on the morphological characteristics of larvae and adults. The most
      parsimonious reconstruction of the "luminous" and "nonluminous" states, based on
      the present molecular phylogeny, indicates that the ancestral state of Elateridae
      was nonluminous. This suggests that the bioluminescence in click beetle evolved
      independent of that of other luminous beetles, such as Lampyridae, despite their
      common mechanisms of bioluminescence.

PMID- 16971142
TI  - Molecular systematics of a speciose, cosmopolitan songbird genus: defining the
      limits of, and relationships among, the Turdus thrushes.
AB  - The avian genus Turdus is one of the most speciose and widespread of passerine
      genera. We investigated phylogenetic relationships within this genus using
      mitochondrial DNA sequence data from the ND3, ND2 and cytochrome b genes. Our
      sampling of Turdus included 60 of the 65 extant species currently recognized, as
      well as all four species from three genera previously shown to fall inside Turdus
      (Platycichla, Nesocichla, and Cichlherminia). Phylogenetic trees based on maximum
      likelihood and maximum parsimony algorithms were congruent. Most of the Turdus
      taxa sampled fall into one of four clades: an African clade, a Central American
      Caribbean clade, a largely South American clade, and a Eurasian clade. Still
      other taxa are placed either at the base of Turdus, or as links between clades.
      In no instance is any continent reciprocally monophyletic for the species
      distributed on it. A general lack of nodal support near the base of the phylogeny
      seems related to a rapid intercontinental establishment of the major clades
      within Turdus very early in the history of the genus. The monotypic genus
      Psophocichla is distantly related to, but clearly the sister of, Turdus rather
      than a constituent member of it.

PMID- 16971144
TI  - A multilocus phylogeny of New World jay genera.
AB  - We studied phylogenetic relationships of the New World Jays (NWJs) based on DNA
      sequences from three mitochondrial and two nuclear loci. Sampling included at
      least two individuals from each of the seven NWJ genera and four outgroups of
      closely related corvids, as well as six of the 16 Cyanocorax species (including
      two representatives of the previously recognized "Cissilopha"). Phylogenetic
      analyses were conducted using maximum parsimony, maximum likelihood, and Bayesian
      analyses for individual genes and a combined dataset. The combined phylogenetic
      analysis supports the basal position of Cyanolyca to all other NWJs, a
      (Cyanocorax (Calocitta, Psilorhinus)) clade, and a ((Cyanocitta, Aphelocoma)
      Gymnorhinus) clade that agrees with a novel morphological synapomorphy uniting
      Cyanocitta and Aphelocoma. Within Cyanocorax, C. yncas (former "Xanthoura") is
      basal to a split among former "Cyssilopha" species and the rest of the Cyanocorax
      species. To explore implications for the historical biogeography of the NJWs, we
      used Dispersal-Vicariance Analysis, which indicated that NWJs originated either
      in Mesoamerica or North America+Mesoamerica, with South American NWJs dispersing
      three times independently from Mesoamerica.

PMID- 16971145
TI  - Phylogeny and temporal diversification of Calomys (Rodentia, Sigmodontinae):
      implications for the biogeography of an endemic genus of the open/dry biomes of
      South America.
AB  - A thorough analysis of character evolution and biogeography of a group is only
      possible with a comprehensive sampling of its diversity. The sigmodontine genus
      Calomys is particularly interesting for the study of neotropical biogeography as
      it occurs exclusively in the dry and grassland biomes: Cerrado, Caatinga, Chaco,
      Pampas, Venezuelan Llanos, Puna, and a diversity of dry forests biomes. Although
      Brazil encompasses a large part of the geographic distribution of the genus and
      at least three endemic species, the last published phylogeny of Calomys included
      only two specimens (both representing the same species) from a single locality in
      this country. In the present paper we add complete cytochrome b sequences of
      Brazilian karyomorphs to previously published sequences in order to provide a
      phylogenetic hypothesis including most of the genus diversity. The main
      objectives of this study were to clarify taxonomic issues related to Brazilian
      karyomorphs and to study the diversification processes of the genus by analyzing
      its biogeography in combination with cladogenesis dates estimated with a
      molecular clock. The phylogeny indicates that at least six different species
      inhabit the Brazilian territory, one of them still undescribed. Date estimates
      indicate that two sequential basal splits, the first separating Andean from
      lowland species and the second isolating species north and south of the Amazonia,
      took place in the Pliocene between 3 and 4 Ma. A large-bodied and speciose clade
      of lowland species associated with dry forests and ecotones of the core Cerrado
      and Chaco areas with adjacent biomes diversified in the Pleistocene. This
      indicates the importance of safeguarding ecotones and the Cerrado at a time where
      this biome is being rapidly destroyed.

PMID- 16971146
TI  - Utility of the nuclear protein-coding gene, elongation factor-1 gamma (EF
      1gamma), for spider systematics, emphasizing family level relationships of
      tarantulas and their kin (Araneae: Mygalomorphae).
AB  - Spider systematics has overwhelmingly relied on morphological characters to
      resolve higher-level phylogenetic questions. Molecular phylogenetic studies of
      spiders above the genus level have been rare, partly because of a paucity of
      characterized genes available for amplification and sequencing. Here we show the
      phylogenetic utility of a new molecular marker, elongation factor-1 gamma (EF
      1gamma) for discerning family level relationships in the spider infraorder,
      Mygalomorphae. We included genomic sequences from 26 mygalomorph genera in 14
      families as well as cDNA sequences from 10 families in the infraorder
      Araneomorphae. We found strong support for the traditional split of mygalomorphs
      into atypoids (Antrodiaetidae, Atypidae, and Mecicobothriidae) and non-atypoids
      (all other families). Some families with multiple generic representatives were
      found to be polyphyletic or paraphyletic, such as the Nemesiidae, Ctenizidae, and
      Hexathelidae. A small portion of genomic EF-1gamma that could be amplified from
      araneomorphs contained a short intron, suggesting that longer genomic sequences
      could not be amplified due to the presence of introns. This intron may be useful
      for intra-familial araneomorph relationships. A tentative timeline for spider
      evolution is proposed using the evolutionary rate of EF-1gamma, estimated to be
      approximately 0.22% pairwise divergence per million years based on a non
      parametric smoothing method (NPRS) and fossil constraints.

PMID- 16971147
TI  - Extracellular oxidative systems of the lignin-degrading Basidiomycete
      Phanerochaete chrysosporium.
AB  - The US Department of Energy has assembled a high quality draft genome of
      Phanerochaete chrysosporium, a white rot Basidiomycete capable of completely
      degrading all major components of plant cell walls including cellulose,
      hemicellulose and lignin. Hundreds of sequences are predicted to encode
      extracellular enzymes including an impressive number of oxidative enzymes
      potentially involved in lignocellulose degradation. Herein, we summarize the
      number, organization, and expression of genes encoding peroxidases, copper
      radical oxidases, FAD-dependent oxidases, and multicopper oxidases. Possibly
      relevant to extracellular oxidative systems are genes involved in
      posttranslational processes and a large number of hypothetical proteins.

PMID- 16971148
TI  - Suppression of the acuH13 and acuH31 nonsense mutations in the
      carnitine/acylcarnitine translocase (acuH) gene of Aspergillus nidulans by the
      G265S substitution in the domain 2 of the release factor eRF1.
AB  - A search for suppressors of the carnitine/acylcarnitine translocase (CACT)
      deficiency in Aspergillus nidulans permitted the identification of the suaE7
      mutation, mapping at a new translational suppressor (suaE) gene. The suaE gene is
      essential in A. nidulans and encodes the eukaryotic release factor 1 (eRF1). The
      suaE7 mutation suppresses two acuH alleles (acuH13 and acuH31), both carrying
      nonsense mutations in the CACT encoding gene that involve the replacement of a
      CAG (Gln) codon with a premature TAG stop codon. In contrast, the suaE7 gene does
      not suppress the acuH20 amber nonsense mutation involving a TGG-->TAG change. The
      phenotype associated to the suaE7 mutation strictly resembles that of mutants at
      the suaA and suaC genes, two translational suppressor genes previously
      identified, suggesting that their gene products might functionally interact in
      translation termination. Sequencing of the suaE7 gene allowed the identification
      of a mutation in the domain 2 of the omnipotent class-1 eukaryotic release factor
      involving the Gly265Ser substitution in the A. nidulans eRF1. This mutation
      creates a structural context unfavourable for normal eRF binding that allows the
      misreading of stop codons by natural suppressor tRNAs, such as the tRNAs(Gln).
      Structural analysis using molecular modelling of A. nidulans eRF1 domain 2
      bearing the G265S substitution and computer simulation results suggest that this
      mutation might impair the necessary conformational changes in the eRF1 to
      optimally recognize the stop codon and simultaneously interact with the peptidyl
      transferase centre of the 60S ribosomal subunit.

PMID- 16971149
TI  - High throughput processing of the structural information in the protein data
      bank.
AB  - The protein data bank (PDB) is the largest, most comprehensive, freely available
      depository of protein structural information, containing more than 37,500
      deposited structures. On one hand, the form and the organization of the PDB seems
      to be perfectly adequate for gathering information from specific protein
      structures, by using the bibliographic references and the informative remark
      fields. On the other hand, however, it seems to be impossible to automatically
      review remark fields and journal references for processing hundreds or thousands
      of PDB files. We present here a family of combinatorial algorithms to solve some
      of these problems. Our algorithms are capable to automatically analyze PDB
      structural information, identify missing atoms, repair chain ID information, and
      most importantly, the algorithms are capable of identifying ligands with their
      respective binding sites.

PMID- 16971150
TI  - Effects of 3-thia fatty acids on expression of some lipid related genes in
      Atlantic salmon (Salmo salar L.).
AB  - In this study, the effects of in vivo administration of 3-thia fatty acids (FAs)
      on lipid metabolism in muscle and liver of Atlantic salmon were investigated.
      Prior to analysis, the fish were kept in tanks supplied with 5 degrees C seawater
      for 20 weeks. The fish were fed fish meal and fish oil (FO)-based diets
      supplemented with either nothing (FO), or 0.3% and 0.6% of the 3-thia FAs
      dodecylthioacetic acid (DTA) and tetradecylthioacetic acid (TTA) respectively.
      The fish grew from an initial weight of 110 g to 220 g in the FO group and to
      approximately 160 g in the 3-thia FA groups. There was a significant higher
      mortality (66%) in fish fed 0.6% TTA than in fish fed the 0.3% DTA (15%) and FO
      diets (15%). None of the 3-thia FA diets affected the lipid content of the salmon
      muscle. The liver index, however, was significantly higher and the total liver
      fat content lower in the TTA group than in the FO group. Both DTA and TTA were
      incorporated into the lipid fraction of muscle and liver (0.4% to 0.9%). There
      were no major differences in the total FA composition of liver and muscle between
      the dietary groups; except for a small increase of n-3 polyunsaturated FAs
      (PUFAs) in liver of the DTA group. The mRNA expression of peroxisome proliferator
      activated receptor (PPAR) alpha, apolipoprotein AI (ApoAI), apolipoprotein CII
      (ApoCII) and low-density lipoprotein receptor (LDL-R) was down-regulated in liver
      of the salmon fed 0.3% DTA. PPARalpha and ApoAI transcripts were also reduced in
      liver of salmon fed 0.6% TTA. Additionally, the hepatic lipoprotein lipase (LPL)
      mRNA level was 3.8 fold increased in TTA fish relative to the FO group. In muscle
      there were no significant changes in gene expression pattern of any of the genes
      investigated. This is the first report on the effects of 3-thia FAs on gene
      expression in Atlantic salmon.

PMID- 16971151
TI  - Consequences of missense mutations for dimerization and turnover of
      alanine:glyoxylate aminotransferase: study of a spectrum of mutations.
AB  - Alanine:glyoxylate aminotransferase (AGT) is a liver peroxisomal enzyme,
      deficiency of which results in primary hyperoxaluria type 1 (PH1). More than 65
      PH1-related mutations are now documented in the AGT gene (AGXT), of which about
      50% are missense. We have generated a spectrum of 15 missense changes including
      the most common PH1 mutation, G170R, and expressed them on the appropriate
      background of the major or minor allele, in an Escherichia coli overexpression
      system and in a rabbit reticulocyte transcription/translation system. We have
      investigated their effects on enzyme activity, dimerization, aggregation, and
      turnover. The effect of pyridoxal phosphate (PLP) on dimerization and stability
      was also investigated. Although all 15 mutant AGTs were expressed as intact
      proteins in E. coli, only three: G41R and G41V on the major allele, and the
      common mutation G170R, resulted in significant amounts of enzymatic activity.
      Dimerization failure was a frequent observation (13/15) except for G41V and
      D183N. Dimerization was poor with S187F but was substantially improved with PLP.
      Proteasome-mediated protein degradation was observed for all the mutations except
      G41R on the major allele, G41V, D183N, G170R, and S218L. Increases in the
      stability of the mutant enzymes in the presence of PLP were small; however, G41R
      on the minor allele showed a direct relationship between its half life and the
      concentration of PLP. The minor allele AGT product and many of the mutants were
      subject to a limited non-proteasomal proteolytic cleavage when ATP was depleted.

PMID- 16971152
TI  - [Uncommon clinical presentation of a gestational choriocarcinoma].
AB  - Gestational choriocarcinoma is a rare malignant tumour with a strong metastatic
      potential. We report a case of a 31-year-old patient with a gestational
      trophoblastic tumor revealed by renal and pulmonary metastases, one year after a
      normal pregnancy. The diagnosis was established by the pathologist on the radical
      nephrectomy specimen. The evolution was quickly favorable after adequate
      treatment using multiagent chemotherapy. This case highlights the polymorphic
      aspects of the gestational choriocarcinoma and stresses the importance of a
      betaHCG assessment anytime abnormal symptoms occur in the outcome of a pregnancy.

PMID- 16971153
TI  - [Effects of estrogens on the development of the testis during fetal and neonatal
      life].
AB  - Estrogens are classically known to play a major role in female reproduction but
      there is now compelling evidence that they may also be involved in the regulation
      of male reproductive function. In humans, a decrease in sperm count and an
      increase in the incidences of testicular cancer, cryptorchidism and hypospadia
      have been observed in many countries over the last 50 years. Male reproductive
      alterations were also observed in wildlife. Such male reproductive disorders have
      been attributed to the increase in concentration of xenobiotics, and of
      xenoestrogens in particular, in the environment and in food. Epidemiological,
      clinical and experimental studies have suggested that excessive exposure to
      estrogens during fetal/neonatal life can lead to reproductive disorders in
      adulthood. Using an in vitro model we showed that estrogens directly affected the
      development of the fetal testis and we evidenced the existence of periods of
      sensitivity throughout development. Lastly, we clearly demonstrated that the
      fetal and neonatal testis is very sensitive to estrogens since the invalidation
      of estrogen receptor alpha leads to an increase of steroidogenesis and the
      invalidation of estrogen receptor beta enhances the development of the germ cell
      lineage in the male.

PMID- 16971154
TI  - Spermatozoal RNA: Why is it there and what does it do?
AB  - The mammalian male gamete is transcriptionally silent as a consequence of the
      highly condensed architecture of its chromatin and there is also little or no
      cytoplasm capable of supporting translation; however, we now understand that
      these cells carry a full complement of mRNAs and that under certain conditions,
      spermatozoa can translate their mRNAs de novo. Moreover, there is now good
      evidence that spermatozoal RNA can potentially affect phenotypic traits in
      offspring. This epigenetic phenomenon may involve the transmission of extra
      chromosomal episomal elements. These data indicate that the spermatozoon is well
      matched to its role of delivering the paternal genome, but that additional male
      benefits may also be accrued by the delivery of spermatozoal RNA.

PMID- 16971155
TI  - [Hysterectomies in patients with no history of vaginal delivery. A study of 243
      cases. Gynecol Obstet Fertil 2005;33:11-16].

PMID- 16971157
TI  - [Alcohol, tobacco and cannabis: Review of teratogenicity studies in animals].
AB  - Despite an intensive national campaign of information, the drugs most frequently
      consumed by young adults undoubtedly continue to be alcohol, tobacco and
      cannabis. If the impact of these drugs on the health of the consumers can be
      evaluated in conjunction with the clinical and epidemiologic data, the
      consequences on the embryo due to their consumption by the pregnant women can be
      appreciated thanks to the abundant literature describing their effects in the
      gravid animal. Taking into account the abundant literature available in multiple
      animal species, the zero drug recommendation should be widely diffused to
      pregnant women.

PMID- 16971158
TI  - Wireless orientation sensors: their suitability to measure head movement for neck
      pain assessment.
AB  - The purpose of this study was to verify the performance and suitability of new
      generation 3D wireless orientations sensors to measure cervical range of movement
      against a criterion standard instrument, an electromagnetic motion analysis
      system (Fastrak-Polhemus). The wireless orientation sensor (InertiaCube 3)
      consists of 9 motion-sensing elements: 3 accelerometers, 3 angular velocity rate
      transducers and 3 magnetometers. Measurements of cervical range of motion in each
      primary plane, left-lateral flexion, flexion and left rotation were directly
      compared from both systems in 10 normal asymptomatic subjects. Results showed
      very high cross-correlations (.99-.97) and low average root mean square errors
      (0.7-2.5 degrees). We conclude that orientation sensors are a valid, accurate and
      suitable device for obtaining cervical joint ranges of motion in the primary
      plane of movement.

PMID- 16971159
TI  - The influence of specific training on trunk muscle recruitment patterns in
      healthy subjects during stabilization exercises.
AB  - Low back pain is a major problem involving high medical costs, therefore
      effective prevention strategies are essential. Stabilization exercises seem to
      facilitate the neuromuscular control of the lumbar spine and may be useful in
      prevention programs. To investigate whether specific lumbar stabilization
      training has an effect on muscle recruitment patterns in a healthy population, in
      the present study 30 subjects were recruited to perform two types of testing
      exercises, i.e. bridging exercises and exercises in four-point kneeling, both
      before and after training. Surface electromyographic data of different abdominal
      and back muscles were obtained. After training, analysis of the relative muscle
      activity levels (percentage of maximal voluntary isometric contraction) showed a
      higher activity of the local (segmental-stabilizing) abdominal muscles, but not
      of the local back muscles; minimal changes in global (torque-producing) muscle
      activity also occurred. Analysis of the local/global relative muscle activity
      ratios revealed higher ratios during all exercises after training, although not
      all differences were significant. These results indicate that muscle recruitment
      patterns can be changed in healthy subjects by means of a training program that
      focuses on neuromuscular control. Additional studies are needed to evaluate this
      type of training as a prevention strategy.

PMID- 16971160
TI  - Initial development of a device for controlling manually applied forces.
AB  - In both simulation and manual therapy studies, substantial variability has been
      shown when therapists attempt to replicate an applied force. Knowledge about the
      forces employed during treatment could reduce this variability. In the current
      project, a prototype for a mobilizing device incorporating a dynamometer was
      constructed. The prototype device was built around a conventional "hand-grip"
      dynamometer to give dial visibility during application of mobilizing forces and a
      moulded handle was used to increase the hand contact surface during force
      application. The variability of the mobilization forces produced was measured,
      and ratings of comfort during a simulated spinal mobilization technique were
      obtained from therapists. METHOD: Thirty physiotherapists were randomly allocated
      to apply either: (i) their own estimate of a grade III mobilization force using
      their hands in a pisiform grip or (ii) a 100N force with the manual therapy
      dynamometer, and to rate comfort during the performance of both techniques on a
      100mm visual analogue scale. RESULTS: Variance in dynamometer-dial-guided force
      application was always significantly less than the variance in therapist-concept
      guided force application. Repeated-measures tests showed that the mean force
      produced at grade III was not significantly different from 100N, but
      physiotherapist comfort ratings were found to be significantly greater (P<0.01)
      when the manual therapy dynamometer was used. CONCLUSION: Manually applied force
      variability was significantly less and therapist comfort greater when using a
      device with visual access to a dial giving immediate force readout.

PMID- 16971161
TI  - Clinical measurement of posterior shoulder flexibility.
AB  - The objectives of this study were to determine both the intra-rater reliability
      and the smallest real difference necessary to detect meaningful clinical changes
      over an 8-12 week period for three clinical measures of posterior shoulder
      flexibility. Posterior shoulder tightness has been associated with abnormal
      humeral head translations that narrow the subacromial space and contribute to
      impingement. Posterior shoulder stretching to normalize joint kinematics is often
      used when treating individuals with subacromial impingement. Currently there is
      no measurement of posterior shoulder flexibility that has been demonstrated to be
      reliable or responsive in patients over a treatment interval. Construction
      workers with overhead work exposure were recruited to an impingement group
      (n=37), and an asymptomatic group (n=22). Three flexibility measurements were
      taken on each subject at baseline and 8-12 weeks later by the same physical
      therapist. Intra-rater reliability was determined using intra-class correlation
      coefficients (ICCs) and standard errors of measurement (SEM). The smallest real
      difference value (SRD) determined the smallest detectable intervention-related
      measurement change over time. ICCs for the three measurements ranged from poor
      (0.40) to good (0.79). The SEM and SRD values reflected high test-retest
      variability in all three measurements. None of the three measures were proven to
      be highly stable indicators of posterior shoulder flexibility over this time
      period, nor were they able to detect small changes over this interval due to the
      high trial to trial variance in a non-intervention sample. Caution should be used
      when interpreting these clinical measurements over prolonged time periods.

PMID- 16971162
TI  - Improved contraction of the transversus abdominis immediately following spinal
      manipulation: a case study using real-time ultrasound imaging.

PMID- 16971163
TI  - Construct validity of lumbar extension measures in McKenzie's derangement
      syndrome.
AB  - The McKenzie treatment model advocates extension-based treatments for sub-groups
      of low back pain (LBP) patients and an improvement in extension range is seen as
      a positive outcome. The treatment model states that patients who fit the McKenzie
      derangement classification respond faster than other patients. The validity of
      this treatment model and of the clinical measures of extension has not yet been
      established. Fifty patients with LBP were classified as derangement (n=40) or non
      derangement (n=10) based on a McKenzie assessment and then treated with extension
      procedures. Lumbar extension was measured in two positions, standing and prone,
      with three methods, inclinometer, Schober and finger tip to floor, on Day 1 and
      Day 5 of treatment. Patients completed a global perceived effect (GPE) scale on
      Day 5. Construct validity was tested, by comparing extension improvement and the
      GPE scores between the two groups. Responsiveness of the six extension measures
      was calculated. All patients gained extension range however the derangement group
      had significantly higher GPE scores and greater improvement in extension range.
      The modified Schober method in standing was the most responsive method for
      measuring lumbar extension. The results of this study support the measurement of
      lumbar extension, for patients, treated with extension procedures and provides
      evidence for the construct validity of one aspect of the McKenzie treatment
      model. The modified Schober method is the preferred protocol for a clinical
      setting.

PMID- 16971164
TI  - Activation of vastus medialis oblique is not delayed in patients with
      osteoarthritis of the knee compared to asymptomatic participants during open
      kinetic chain activities.
AB  - This study investigated whether the onset of electromyographic (EMG) activity of
      vastus medialis oblique (VMO) was delayed relative to that of vastus lateralis
      (VL) in patients with osteoarthritis (OA) of the knee compared to asymptomatic
      participants during open kinetic chain activities. An exploratory observational
      cross sectional study was carried out. Two groups were tested, symptomatic OA
      knee patients, diagnosed by an orthopaedic surgeon, (n=17), mean (SD) age 66.0
      (7.6) years, and asymptomatic participants (n=17), 56.7 (8.6) years. Surface EMG
      activity of VMO and VL was measured, during concentric contractions extending the
      knee from 90 degrees flexion, and during maximal voluntary isometric contractions
      at 60 degrees knee flexion. The EMG onset times of VMO and VL were determined
      visually and by algorithm. The onset timing difference (OTD) between the two
      muscles was calculated for each subject, by subtracting the onset time of VL from
      VMO. Mann-Whitney U-tests revealed that the OTD between VMO and VL was not
      significantly different between the groups during either contraction type (both
      p>0.05). The results of this exploratory study may have implications for
      rehabilitation programmes aimed at developing preferential activation of VMO
      compared to VL in OA knee patients.

PMID- 16971165
TI  - Cadmium induced mitochondrial injury and apoptosis in vero cells: protective
      effect of diallyl tetrasufide from garlic.
AB  - Oxidative stress and mitochondrial injury has been implicated in cadmium-induced
      apoptosis. In this study, we examined the protective effect of diallyl
      tetrasulfide from garlic on cadmium induced oxidative stress and apoptosis in
      vero cells. Exposure of vero cells to cadmium (10 microM) for 18 h showed the
      apoptotic events such as loss of cell viability, alterations in nuclear
      morphology and decreased mitochondrial membrane potential with significantly
      increased levels of reactive oxygen species (super oxide anion and hydrogen
      peroxide). Treatment of vero cells with cadmium (10 microM) and diallyl
      tetrasulfide (5-50 microg/ml) showed that diallyl tetrasulfide attenuated the
      cadmium-induced suppression of cell viability in a dose dependent manner and
      highly significant effect was observed at 40 microg/ml. The nuclei morphological
      analysis with 4',6-diamidino-2-phenylindole staining confirmed that diallyl
      tetrasulfide at 40 microg/ml prevented the Cd (10 microM) induced apoptosis. Flow
      cytometric analysis with 2',7'-dichlorofluorencein diacetate showed that the
      inhibitory effect of diallyl tetrasulfide (10-40 microg/ml) on reactive oxygen
      species generation parallel with its effect on cell viability. In addition,
      diallyl tetrasulfide (40 microg/ml) remarkably reduced the cadmium-induced
      accumulation of superoxide radical and hydrogen peroxide with in cells. Further,
      diallyl tetrasulfide significantly protected the cadmium-induced decrease in
      mitochondrial membrane potential, an indicator of mitochondrial function. Our
      study suggest that diallyl tetrasulfide affect the reactive oxygen species
      generation induced by cadmium, and possesses a novel protective effect on the
      cytolethality associated with mitochondrial injury, which contributes to the
      antiapoptotic effect of diallyl tetrasulfide against cadmium.

PMID- 16971166
TI  - Thrombospondin-1 C-terminal-derived peptide protects thyroid cells from ceramide
      induced apoptosis through the adenylyl cyclase pathway.
AB  - Thrombospondin-1, a multi-modular matrix protein is able to interact with a
      variety of matrix proteins and cell-surface receptors. Thus it is
      multifunctional. In this work, we examined the role of thrombospondin-1 in
      ceramide-induced thyroid apoptosis. We focused on the VVM containing sequence
      localized in the C-terminal domain of the molecule. Primary cultured thyroid
      cells synthesize thrombospondin-1 depending on their morphological organization.
      As it leads thyrocytes to organize into monolayers before inducing apoptosis
      ceramide can modulate this organization. Here, we established that C(2)-ceramide
      treatment decreased thrombospondin-1 expression by interfering with the adenylyl
      cyclase pathway, thus leading to apoptosis. Furthermore, we demonstrated that the
      thrombospondin-1-derived peptide 4N1 (RFYVVMWK) abolished ceramide-induced
      thyroid cell death by preventing intracellular cAMP levels from dropping.
      Finally, we reported that 4N1-mediated inhibition of ceramide-induced apoptosis
      was consistently associated with a down-regulation of the caspase-3 processing.
      Integrin-associated protein receptor (IAP or CD47) was identified as a molecular
      relay mediating the observed 4N1 effects. Taken together, our results shed light
      for the first time on anti-apoptotic activities of the thrombospondin-1-derived
      peptide 4N1 and provide new information on how thrombospondin-1 may control
      apoptosis of non-tumoral cells.

PMID- 16971167
TI  - Involvement of calpains in growth factor-mediated migration.
AB  - Previous research in our laboratory has already shown the importance of the role
      played by ubiquitous calpains during myoblast migration. The aim of this study
      was to investigate calpain expression during myoblast migration and, to enhance
      this phenomenon via calpain stimulation. Ubiquitous calpains are members of a
      large family of calcium-dependent cysteine proteases. They play an important role
      in numerous biological and pathological phenomena, such as signal transduction,
      apoptosis, cell-cycle regulation, cell spreading, adhesion, invasion, myogenesis,
      and motility. Myoblast migration is a crucial step in myogenesis, as it is
      necessary for myoblast alignment and fusion to form myotubes. This study started
      by examining changes in calpain expression during migration, then investigated
      the possibility of activating myoblast migration via the stimulation of calpain
      expression and/or activity. The migration rate of myoblasts overexpressing mu- or
      milli-calpain was quantified. The results showed that calpain overexpression
      dramatically inhibited myoblast migration. Growth-factor treatments were then
      used to enhance myoblast migration. The results showed that treatment with IGF-1,
      TGF-beta1, or insulin induced a major increase in migration and caused a
      significant increase in m-calpain expression and activity. The increase in
      migration was totally inhibited by adding calpeptin, a calpain-specific
      inhibitor. These findings suggest that milli-calpain is involved in growth factor
      mediated migration.

PMID- 16971169
TI  - Dielectric spectroscopy analysis in employing liquid crystal phthalonitrile
      derivative in nematic liquid crystals.
AB  - Dielectric anizotropy and relaxation properties of 2,3-dicyano-1,4-di[3,4,5
      tri(dodecyloxy)phenylcarbonyloxy] benzene (DCDPB)-doped E7 and E7 liquid crystal
      have been investigated by the dielectric spectroscopy method. Dielectric
      anisotropy property of the LCs changes from the positive type to negative type.
      Dielectric relaxation properties suggest that LCs exhibit a monodispersive
      dielectric property. The relaxation frequency of E7 and E7/DCDPB liquid crystals
      was calculated by means of Cole-Cole plots. Consequently, DCDPB dopant changes
      the dielectric anizotropy and relaxation parameters of E7 LC.

PMID- 16971168
TI  - Ryk: a novel Wnt receptor regulating axon pathfinding.
AB  - Members of the Wnt family and their receptors, the Frizzleds, are key regulators
      of pivotal developmental processes including embryonic patterning, specification
      of cell fate, and determination of cell polarity. The versatility and complexity
      of Wnt signaling has been further highlighted by the emergence of a novel family
      of Wnt receptors, the Ryk family. In mammals and flies, Ryk is a key
      chemorepulsive axon guidance receptor responsible for the establishment of
      important axon tracts during nervous system development. Although the function of
      Ryk is currently best understood with respect to this role, its widespread
      expression, both in developing tissues and in the adult, suggests that Ryk may
      regulate many essential biological processes. This hypothesis is supported by the
      multiple developmental phenotypes apparent in Ryk loss-of-function mice. These
      mice display a variety of embryonic abnormalities, including disruption of
      skeletal, craniofacial and cardiac development. Here we review Ryk structure and
      function focusing on its activity as an axon guidance receptor.

PMID- 16971170
TI  - Dipole moments studies of fluorenone and 4-hydroxyfluorenone.
AB  - Electronic absorption, excitation and fluorescence spectra of fluorenone and 4
      hydroxyfluorenone were recorded at room temperature in several aprotic solvent of
      varying polarities. The ground (mu(g)) and excited (mu(e)) state dipole moments
      of both molecules were estimated from solvatochromic shifts of absorption and
      fluorescence spectra as a function of the dielectric constant (epsilon) and
      refractive index (n). These experimental results were completed with theoretical
      results of quantum chemical calculations (AM1). The experimental and theoretical
      dipole moments in the ground state were compared. It was determined that dipole
      moments of excited state were higher than those of the ground state for both
      molecules.

PMID- 16971171
TI  - An e-consent-based shared EHR system architecture for integrated healthcare
      networks.
AB  - OBJECTIVES: Virtual integration of distributed patient data promises advantages
      over a consolidated health record, but raises questions mainly about
      practicability and authorization concepts. Our work aims on specification and
      development of a virtual shared health record architecture using a patient
      centred integration and authorization model. METHODS: A literature survey
      summarizes considerations of current architectural approaches. Complemented by a
      methodical analysis in two regional settings, a formal architecture model was
      specified and implemented. RESULTS: Results presented in this paper are a survey
      of architectural approaches for shared health records and an architecture model
      for a virtual shared EHR, which combines a patient-centred integration policy
      with provider-oriented document management. An electronic consent system assures,
      that access to the shared record remains under control of the patient. A
      corresponding system prototype has been developed and is currently being
      introduced and evaluated in a regional setting. CONCLUSION: The proposed
      architecture is capable of partly replacing message-based communications.
      Operating highly available provider repositories for the virtual shared EHR
      requires advanced technology and probably means additional costs for care
      providers. Acceptance of the proposed architecture depends on transparently
      embedding document validation and digital signature into the work processes. The
      paradigm shift from paper-based messaging to a "pull model" needs further
      evaluation.

PMID- 16971172
TI  - Comparison of clinical features of acute hepatitis caused by hepatitis E virus
      (HEV) genotypes 3 and 4 in Sapporo, Japan.
AB  - In Japan, indigenous acute hepatitis E is not a rare disease, and is mainly
      caused by hepatitis E virus (HEV) genotypes 3 and 4. Whether there is a
      difference in clinical features between the two genotypes remains unclear. This
      study compares the clinical features of patients infected with the two. From
      January, 1994, to December, 2003, 9 infected with HEV genotype 3 and 27 patients
      with genotype 4 were enrolled. Patients with genotype 4 had significantly higher
      peak alanine aminotransferase levels (median 3430IU/L, interquartile range 1747
      4763 versus 1052IU/L, 845-2707; p=0.01). The lowest prothrombin time was lower in
      the genotype 4 group (61%, 42-77 versus 84%, 70-96; p=0.05). In our series,
      patients with genotype 4 had longer median duration of hospital stay (26.5 days,
      18-31 versus 18 days, 12-23.5; p=0.06). The patients with genotype 4 infection
      tended to have more severe clinical manifestations than those with genotype 3
      infection.

PMID- 16971173
TI  - Measurement of hepatitis B virus core-related antigen as predicting factor for
      relapse after cessation of lamivudine therapy for chronic hepatitis B virus
      infection.
AB  - BACKGROUND: Prolonged lamivudine therapy has two major problems: breakthrough
      hepatitis during treatment and relapse of aminotransferase (ALT) after cessation
      of the therapy. The aim of this study was to examine factors that could predict
      ALT flare after stopping lamivudine therapy. METHODS: We analyzed 22 Japanese
      patients with chronic hepatitis B infection, in whom lamivudine therapy was
      stopped after HBV DNA level had been gone undetectable (<3.7LGE/ml) during at
      least six consecutive months. The post-treatment followed up was carried for 28
      months in median (range 9-41). HBV core-related antigen (HBcrAg) assay was
      assessed using newly developed assay. RESULTS: After cessation of lamivudine
      therapy, 11 patients (50%) had relapsed (reactivation of serum ALT >80IU/l,
      relapsers) and remaining 11 (50%) did not relapse (non-relapsers). In the
      univariate comparison of relapsers versus non-relapsers, HBcrAg level at
      lamivudine cessation point (4.5+/-1.0 versus 3.4+/-0.9; p=0.0145) has been shown
      as a significant predictive factor for non-relapse. All patients with HBcrAg
      <3.0logU/ml at the cessation point had no ALT flares. Multivariate analysis on
      effects of 10 factors (age, sex, cirrhosis, pretreatment ALT level, HBV DNA
      level, HBcrAg level, mean months till undetectable HBV DNA, duration of
      undetectable HBV DNA and HBcrAg level at lamivudine cessation point), indicated
      that HBcrAg level at lamivudine cessation point <3.4log U/ml was the only
      independent predictive factor for absence of the post-treatment relapse.
      CONCLUSIONS: HBcrAg level at lamivudine cessation point might be useful as a
      prognostic predictor of response to lamivudine therapy cessation. The measurement
      of HBcrAg is a useful additional test for monitoring chronic HBV infection.

PMID- 16971174
TI  - Effect of iron reduction by phlebotomy in Japanese patients with nonalcoholic
      steatohepatitis: A pilot study.
AB  - Increased hepatic iron deposition may play a role in the pathogenesis of
      nonalcoholic steatohepatitis (NASH). This study aimed to test whether iron
      removal by phlebotomy improves serum transaminase activities in patients with
      NASH. Eleven patients (six males and five females) with biopsy-proven NASH
      underwent phlebotomy biweekly until they reached near-iron deficiency (NID)
      (serum ferritin concentration lower than or equal to 30ng/ml). Nine patients
      completed this study. Serum ferritin levels in these patients fell from 563+/-322
      to 18+/-9ng/ml (p=0.001). The treatment reduced mean serum alanine
      aminotransferase (ALT) activity from 126+/-47 to 56+/-17IU/l (p=0.002). Their
      weight did not change significantly throughout the study period. Although two
      patients withdrew from the study, none was affected by any side effects of
      repeated phlebotomy that required discontinuing the treatment. In conclusion,
      this pilot study suggests that iron reduction therapy by phlebotomy will be one
      of the promising therapies for NASH.

PMID- 16971175
TI  - Real-time PCR for mumps diagnosis on clinical specimens--comparison with results
      of conventional methods of virus detection and nested PCR.
AB  - BACKGROUND: Since November 2003, the UK has seen a dramatic rise in the number of
      mumps cases, resulting in increasing demands on virology laboratories to confirm
      mumps infection in a timely and efficient manner. Traditional mumps virus
      detection methods are often insensitive, lengthy, and cumbersome. Some
      laboratories in the UK now use molecular methods that are based on nested
      polymerase chain reaction (PCR). Early serological diagnosis often relies on
      detection of anti-mumps IgM, which may be absent in the first 10 days of illness.
      OBJECTIVES: We compared a one-step real-time RT-PCR with an established nested
      PCR (SH-PCR) and virus detection by culture and antigen detection, and assessed
      the clinical usefulness of mumps real-time PCR for diagnosis from CSF. STUDY
      DESIGN: In total, 280 clinical samples were investigated by real-time PCR, nested
      PCR and a combination of traditional virus detection methods (antigen detection
      on oral samples, cell culture on all samples). Furthermore, 88 CSF samples
      submitted for diagnosis of possible viral meningitis were analysed by real-time
      PCR. RESULTS: The real-time PCR detected the highest number of positive oral
      samples (119/180) compared to SH-PCR (92/180) and combined virus culture and
      antigen detection procedures (90/180). Sensitivity of mumps virus detection in
      urine was poor for all three methods: 34.0% (traditional detection), 29.8% (real
      time PCR) and 2.1% (SH-PCR), respectively. Real-time PCR on 88 CSF samples
      identified five patients with mumps meningitis, significantly increasing viral
      diagnosis in this cohort. CONCLUSION: Real-time PCR on oral samples is the
      investigation of choice for mumps infection. Mumps virus detection in urine by
      any of the PCRs used was clearly less successful. Real-time PCR on CSF samples
      seems a promising adjunct for diagnosis of mumps meningitis, especially in an age
      group with high incidence of mumps.

PMID- 16971176
TI  - A modified single-tube one-step product-enhanced reverse transcriptase (mSTOS
      PERT) assay with heparin as DNA polymerase inhibitor for specific detection of
      RTase activity.
AB  - BACKGROUND: Current regulations and recommendations proposed for the production
      of vaccines in continuous cell lines of any origin demand that these be free of
      exogenous viruses, particularly retroviruses. Recently, the ultra-sensitive
      product-enhanced reverse transcriptase (PERT) assay can be used to detect minute
      of reverse transcriptase (RTase) in single retroviral particle and is 10(6) times
      more sensitive than the conventional RTase assays. However, coincidental with
      this increase in sensitivity is an increase in false-positive reactions derived
      from contaminating cellular DNA polymerases, which are known to have RTase-like
      activities. OBJECTIVES: To develop a modified single-tube one-step PERT (mSTOS
      PERT) assay with improvements on decreasing significantly the level of false
      positive reactions, and to evaluate the mSTOS-PERT assay for sensitivity and
      specificity. STUDY DESIGN: Ampliwaxtrade mark was used to compartmentalize the
      reverse transcription (RT) and PCR step in the same micro-tube with more
      efficiency and reproducibility, while maintaining the high sensitivity. The DNA
      amplification products were separated by 2% agarose gel electrophoresis, and then
      analyzed by non-isotopic Southern blot hybridization. A wide variety of cell
      lines used in biologicals production were detected to validate the improved mSTOS
      PERT assay. RESULTS: The detection limit for the mSTOS-PERT assay was at least
      10(-9)U, when using AMV-RTase as a positive control. Furthermore, heparin
      involvement in the RT step can eliminate completely the false-positive PERT
      signals which are exhibited by cellular polymerases such as DNA-dependent DNA
      polymerase alpha, gamma released by cell death. Most mammalian cells (MRC-5,
      Vero, WISH, 2BS, RK-13, MDCK, etc.) are PERT-negative in cell supernatants. Some
      PERT-positive signals in cell lysates were found to be introduced by the cellular
      DNA polymerases and could be inhibited specifically by heparin. Chick cells
      derived from either chick embryo fibroblasts (CEF) or allantoic fluid from SPF
      embryonated eggs, murine hybridoma cell SP2/0, etc., contained authentic RTase
      activities, which could not be inactivated by heparin. CONCLUSIONS: The improved
      mSTOS-PERT assay described here may distinguish the genuine RTase activity from
      cellular polymerases with high sensitivity and specificity, and is rapid and easy
      to perform to screen for the possible contamination of minute retroviruses in the
      cell substrates used in vaccine production.

PMID- 16971177
TI  - Changes in seroprevalence to four herpesviruses over 30 years in Swedish children
      aged 9-12 years.
AB  - BACKGROUND: Changing social conditions and life-styles in Sweden may have
      affected the spread of varicella-zoster virus (VZV), herpes simplex virus (HSV),
      cytomegalovirus (CMV), and Epstein-Barr virus (EBV). OBJECTIVES: To study
      possible changes over 30 years in prevalence of antibodies against VZV, HSV, CMV,
      and EBV in Swedish children, using modern serological methods. STUDY DESIGN:
      Serum samples from 819 Swedish children who were 9-12 years old in 1967-1968, in
      1977-1978 (two cohorts), and in 1997, respectively, were examined. IgG antibodies
      against VZV, HSV, and CMV were measured by well validated enzyme-linked
      immunosorbent assays and against EBV by indirect immunoflourescense. RESULTS: The
      seropositivity for VZV for 9-12 years old children was 50% in 1967-1968, 74-82%
      in 1977-1978, and 98% in 1997. The corresponding figures were 31%, 53%, 50%, and
      58% for CMV, 35%, 35%, 32%, and 38% for HSV, and 64% in 1967-1968 and in 1977
      1978 (both cohorts), and 62% in 1997 for EBV. CONCLUSIONS: The seroprevalence for
      VZV increased significantly from 1967-1968 to 1997, and there was also a
      significant but smaller increase in the CMV seroprevalence, while seroprevalence
      to HSV and EBV remained relatively stable.

PMID- 16971178
TI  - Influenza virus infections in Yangon, Myanmar.

PMID- 16971179
TI  - The great escape: do parasites break Dollo's law?
AB  - A long-held assumption in evolutionary studies is that a character that changes
      from a complex to a simple state is unlikely to return to the same complex state.
      The extreme version of this assumption has been codified as Dollo's law.
      Unfortunately, this paradigm has supported the idea that simple and complex
      traits are qualitatively different, when it is more sensible to suggest that
      there is a quantitative difference. Dollo's law has been the predominant paradigm
      in parasitology, where a move from a free-living state to parasitism has been
      considered a unidirectional pathway or 'one-way trip' because organisms lose the
      structures required to return to the free-living state. Several recent studies
      have suggested that complex structures can be regained from simple traits, and we
      suggest that this is also possible for parasites.

PMID- 16971180
TI  - RNAi in Haemonchus contortus: a potential method for target validation.
AB  - RNA interference (RNAi) is a method for the functional analysis of specific
      genes, and is particularly well developed in the free-living nematode
      Caenorhabditis elegans. There have been several attempts to apply this method to
      parasitic nematodes. In a recent study undertaken in Haemonchus contortus,
      Geldhof and colleagues concluded that, although a mechanism for RNAi existed, the
      methods developed for RNAi in C. elegans had variable efficacy in this parasitic
      nematode. The potential benefits of RNAi are clear; however, further studies are
      required to characterize the mechanism present in parasitic nematodes, and to
      improve culture systems for these nematodes to monitor the long-term effects of
      RNAi. Only then could RNAi become a reliable assay of gene function.

PMID- 16971181
TI  - A case of 'hit-and-run' in Plasmodium genetics.
AB  - The ability to genetically manipulate species of the genus Plasmodium, some of
      which are causative organisms of malaria, has seen significant advances in the
      past 13 years. However, one major tool that has been lacking is the ability to
      undertake reverse genetics and 'hit-and-run' mutagenesis. This deficiency has
      been addressed in the Plasmodium berghei model.

PMID- 16971182
TI  - Mathematical models and lymphatic filariasis control: monitoring and evaluating
      interventions.
AB  - Monitoring and evaluation are crucially important to the scientific management of
      any mass parasite control programme. Monitoring enables the effectiveness of
      implemented actions to be assessed and necessary adaptations to be identified; it
      also determines when management objectives are achieved. Parasite transmission
      models can provide a scientific template for informing the optimal design of such
      monitoring programmes. Here, we illustrate the usefulness of using a model-based
      approach for monitoring and evaluating anti-parasite interventions and discuss
      issues that need addressing. We focus on the use of such an approach for the
      control and/or elimination of the vector-borne parasitic disease, lymphatic
      filariasis.

PMID- 16971183
TI  - Competitive displacement in Triatominae: the Triatoma infestans success.
AB  - Brazil has just been certificated by Pan American Health Organization as 'free of
      Chagas disease transmission due to Triatoma infestans'. During the early 1980s,
      this species of blood-sucking bug alone was considered responsible for
      approximately 80% of Chagas disease transmission. But it was not always so. The
      species originally abundant in houses of central and eastern Brazil was
      Panstrongylus megistus, which seems to have been progressively displaced from
      houses by T. infestans during the past century. Indeed, T. infestans seems able
      to displace other Triatominae in artificial environments. Recent studies suggest
      that it might simply be because T. infestans feeds more efficiently than its
      Triatominae competitors.

PMID- 16971184
TI  - Establishing a statistic model for recognition of steroid hormone response
      elements.
AB  - Identification of hormone response elements (HREs) is essential for understanding
      the mechanism of hormone-regulated gene expression. To date, there has been a
      lack of effective bioinformatics tools for recognition of specific HRE such as
      Progesterone Response Elements (PRE). In this paper, a comprehensive survey and
      comparison of in silico methods is conducted for establishing a more accurate
      statistic model. Homogeneity of steroid HRE is analyzed and a reliable training
      dataset is constructed through extensive searching for experimentally validated
      response elements from more than 150 literature sources. Based on the observation
      that the verified HREs carry di-nucleotide preservation in comparison with
      uniform nucleotide distributions, both mono and di-nucleotide Position Weight
      Matrices are computed to extract the statistic pattern of the positions. It is
      followed by the sequence transition pattern recognition using a specifically
      designed profile Hidden Markov Model. Reciprocal combination of the statistic and
      transition patterns significantly improves the performance of the model in terms
      of higher sensitivity and specificity. Upon acquisition of the putative response
      elements in the promoter areas of vertebrate genes, a qualitative scheme is
      applied to assess the probability for each gene to be a hormone primary target.
      Using >650 records of experimentally validated steroid hormone response elements,
      a high sensitivity level of 73% and high specificity level of one prediction per
      8.24 kb is reached, allowing this model to be used for further prediction of
      primary target genes through the analysis of their upstream promoters, for human
      or other vertebrate genomes of interest. Additional documents, supplementary data
      and the web-based program developed for response elements prediction are freely
      available for academic research at . Submission of putative gene promoter regions
      for recognition of potential regulatory PREs can be as long as 5 kb.

PMID- 16971185
TI  - Disfluent speech in patients with partial epilepsy: beneficial effect of
      levetiracetam.
AB  - PURPOSE: The aim of this study was to evaluate the clinical effects of
      levetiracetam (LEV) in patients with partial epilepsy and disfluent speech.
      METHODS: Five consecutive patients with partial epilepsy and disfluent speech
      resulting from developmental or neurogenic stuttering were enrolled in a 9-week,
      open-label, prospective study. LEV was given in combination with carbamazepine
      (CBZ) or phenytoin (PHT) at dosages ranging from 500 to 1500mg twice daily. The
      severity of stuttering was assessed with the verbal fluency test (VFT), and with
      the patient global impression of improvement (PGI), at baseline and after 9weeks.
      Electroencephalography and serum monitoring of CBZ and PHT levels were done
      before and after the study. Seizure frequency was monitored. RESULTS: After LEV
      therapy, verbal fluency for all patients, as measured by the VFT, improved from
      25% at baseline to 64%, as did the speed of oral reading, from 5 to 23%. On the
      PGI, all patients rated themselves as better and as having less disfluent speech
      after LEV therapy. For four patients with incomplete control of their seizures,
      the seizure count decreased by more than 50% after LEV therapy. The beneficial
      effect of LEV on verbal disfluency demonstrated on the PGI persisted for the
      entire period of observation, which ranged from 7 to 11 months. CONCLUSIONS: As
      an add-on therapy, LEV seems to improve verbal fluency in patients with partial
      epilepsy and disfluent speech. This effect seems unrelated to the antiepileptic
      activity of the drug. A placebo-controlled trial of LEV in patients with this
      kind of verbal disfluency is warranted.

PMID- 16971186
TI  - Pathological fractures in epilepsy.
AB  - Fracture rates in epilepsy are two to three times that for the general
      population, although the influence of gender and age is not well defined. We
      examined, over a 7-year period at a single health care center, 750 patients with
      epilepsy who sustained the fractures. Among these patients, 293 (39%) had
      pathological fractures and 457 (61%) had traumatic/seizure-related fractures.
      Pathological fractures accounted for 71% of the 146 patients >60 years, a group
      traditionally at risk for pathological fractures (P<0.02). Fractures in epilepsy
      are distributed with bimodal peaks in the fifth and eighth decades of life,
      although pathological fractures are a significant contributor across the life
      span, accounting for 20 to 40% of patients traditionally thought not to be at
      risk for involutional osteoporotic fractures. Together these findings suggest
      that epilepsy, and/or its treatment, is a dominant influence in the pathogenesis
      of fractures and may exacerbate the effects of aging-related involutional
      osteoporosis.

PMID- 16971187
TI  - Impact of epilepsy characteristics and behavioral problems on school placement in
      children.
AB  - Children with epilepsy are known to be prone to educational underachievement as a
      result of learning and behavioral problems. This cross-sectional study evaluated
      the effects of the characteristics of epilepsy and behavioral problems on school
      placement. One hundred eighty-five children aged between 3 and 16 years with
      nonoccasional epileptic seizures were included; 82 were mainstreamed in regular
      schools and 103 were in specialized medical and educational institutions for
      children with epilepsy. Gender distribution and age were comparable for the two
      groups. Logistic regression analysis indicated a statistically significant effect
      for age at onset, generalized nonidiopathic epileptic syndromes, number of
      antiepileptic drugs and behavioral problems, as dominant factors explaining the
      type of school placement. No significant effect was found for the state of
      seizure control. By use of a parent-rated behavior questionnaire, children in
      special institutions were shown to have significantly more problems in the
      hyperactivity/attention deficit and sociability domains. Later age at onset of
      epilepsy was related to more depression/anxiety.

PMID- 16971188
TI  - High school students' knowledge, attitude, and practice with respect to epilepsy
      in Kerala, southern India.
AB  - Very little information is available on knowledge, attitude, and practice (KAP)
      with respect to epilepsy among schoolchildren from developing countries. We
      quantified KAP with respect to epilepsy among 1213 tenth-grade students of
      Kerala, southern India. Ninety-eight percent of them had heard or read about
      epilepsy. However, nearly 60% of students thought that epilepsy was a form of
      insanity. Allopathic treatment was preferred by more than half of the
      respondents; however, many had faith in exorcism and visiting religious places as
      ways to cure epilepsy. Half of the students considered epilepsy a hindrance to
      education, employment, and marriage. Thirteen percent would be unwilling to sit
      adjacent to or play with a child with epilepsy. We conclude that although
      familiarity with epilepsy was high among high school students in Kerala,
      misconceptions and negative attitudes were alarmingly high. Persistent and
      effective information campaigns, therefore, are necessary to change their
      attitudes toward fellow students with epilepsy.

PMID- 16971189
TI  - Polymorphism of gp15/400 allergen gene of W. bancrofti from different regions of
      India endemic for lymphatic filariasis.
AB  - Nematode polyprotein allergens (NPA) are lipid binding/transport molecules that
      elicit elevated levels of IgE response in the infected host, leading to Th2 type
      of immune response. They also transport arachidonic acid and its metabolites that
      are known to be involved in the action of antifilarial drug, Diethylcarbamazine
      and hence are of great significance for the control of lymphatic filariasis. We
      investigated the polymorphism of gp15/400 polyprotein of 35 isolates of lymphatic
      filarial parasite Wuchereria bancrofti collected from different geographic
      locations of India. The repeat sub-unit of the gene was found to be highly
      conserved in all the isolates with only two nucleotide synonymous changes at
      positions 286 (A-G) and 337 (C-T). Since this molecule is highly conserved and
      has multifarious roles in the survival and pathogenesis of the parasite it has
      good potential as a target for drug, immunodulation tool and immunotherapy
      development.

PMID- 16971190
TI  - The influence of pulmonary receptors on respiratory drive in a rabbit model of
      pulmonary emphysema.
AB  - We have observed that pulmonary rapidly adapting receptor activity is greater in
      emphysematous rats than in controls. Pulmonary receptor activity, if modified by
      lung disease, may produce an inappropriate drive to breathe which may be
      perceived as dyspnoea. To investigate the efferent (drive) component of this
      hypothesis respiratory drive (phrenic nerve activity) was recorded in a rabbit
      model of emphysema. Drive was measured as slope and peak height of phrenic nerve
      activity. Slope and peak height were greater in emphysematous rabbits than
      controls, by 28% and 34%, respectively. Block of slowly adapting pulmonary
      stretch receptors by inhaled sulphur dioxide (which left only rapidly adapting
      and C-fibre receptors active) decreased drive in control (slope: 38.89+/-2.29 to
      24.09+/-1.26, P<0.01) but not emphysematous rabbits (slope: 49.92+/-4.11 to
      54.51+/-5.28, NS). Subsequent vagotomy decreased drive in emphysematous rabbits
      (slope: 54.51+/-5.28 to 41.41+/-3.90, P<0.05) but not controls (24.09+/-1.26 to
      23.07+/-1.84, NS). Increased rapidly adapting receptor activity may, in part,
      increase respiratory drive in emphysema. This vagal component is only part of the
      total increased drive which may be perceived as dyspnoea in man.

PMID- 16971191
TI  - On-line sample extraction and enrichment of non-steroidal anti-inflammatory drugs
      by pre-column in capillary liquid chromatography mass spectrometry.
AB  - A rapid and sensitive analytical method has been developed for the simultaneous
      determination of 16 non-steroidal anti-inflammatory drugs (NSAIDs) in human
      plasma by capillary liquid chromatography (LC) and quadrupole mass spectrometry
      with electrospray ionization operated in the negative ion mode. The sample clean
      up and enrichment on a pre-column were accomplished on-line to improve the
      sensitivity. This method greatly reduced sample preparation time and sample
      volume compared with off-line sample extraction methods and conventional LC
      methods, respectively. The recoveries of NSAIDs from human plasma were 56.7
      96.9%. The total analytical time for a single analytical run was approximately 15
      min. The detection limits of NSAIDs were 0.001-0.075 microg ml(-1) using a
      selected ion monitoring mode.

PMID- 16971192
TI  - Single hair analysis of methamphetamine and amphetamine by solid phase
      microextraction coupled with in matrix derivatization.
AB  - A sensitive method for detection of methamphetamine (MA) and amphetamine (AP) in
      human hair was developed using solid phase microextraction (SPME) and one-pot
      derivatization. MA and AP were directly derivatized to N-propoxycarbonyl
      derivatives in an aqueous solution by propylchloroformate in a one-pot reaction
      before extraction by SPME. The derivatives were extracted to a coating of SPME
      from a headspace of the vial. The adsorbed derivatives were thermally desorbed in
      the injection port of a gas chromatograph. Pentadeuterated MA was used as an
      internal standard. The absolute recoveries of MA and AP from the spiked hair were
      2.80-17.5%, respectively. The calibration curves showed linearity in the range of
      0.05-20 ng/0.08 mg/vial for MA and 0.1-20 ng/0.08 mg/vial for AP in hair.
      Detection limits (S/N = 3) of MA and AP were 0.02 and 0.05 ng/0.08 mg/vial. The
      coefficients of variation of intraday were 1.04-26.4%. Additionally, this
      proposed method was applied to segmental analysis in clinical and medico-legal
      cases of MA intoxication.

PMID- 16971193
TI  - Exploiting heparin-binding properties of MoMLV-based retroviral vectors for
      affinity chromatography.
AB  - Chromatography is deemed the most promising technology for large-scale
      purification of viral vectors. The authors have previously shown that heparin
      affinity chromatography could be successfully employed for the purification of
      VSV-G pseudotyped Moloney murine leukemia virus (MoMLV)-derived vectors giving
      excellent results in terms of recovery of active particles, reproducibility and
      selectivity. In this study, the authors examined whether the ability of
      retrovirus particles to specifically bind to heparin ligands is restricted to VSV
      G pseudotypes produced by 293-based packaging cells. It is shown that VSV-G
      deficient retrovirus particles are captured by a heparin chromatography column as
      efficiently as VSV-G containing particles. Most strikingly, RD114 pseudotyped
      retrovirus particles derived from a HT1080-based cell line were found to bind
      heparin with the same affinity as 293-derived VSV-G pseudotypes. RD114
      pseudotyped retrovirus particles were successfully isolated using heparin
      affinity chromatography obtaining good recoveries of functional particles (43%).
      These results indicate that heparin affinity chromatography can be extended to
      the purification of retroviral vectors produced by different packaging cell lines
      independently of the Env-protein used for pseudotyping.

PMID- 16971194
TI  - Development and evaluation of an efficient HPLC/MS/MS method for the simultaneous
      determination of pseudoephedrine and cetirizine in human plasma: application to
      phase-I pharmacokinetic study.
AB  - A sensitive, simple and highly selective liquid chromatography/tandem mass
      spectrometry (LC/MS/MS) method was developed and evaluated to determine
      simultaneously the concentrations of pseudoephedrine and cetirizine in human
      plasma. The chief benefit of the present method is the minimal sample
      preparation, as the procedure is only one-step protein precipitation. Two drugs
      were separated on a C(8) column and analyzed by LC/MS/MS using positive
      electrospray ionisation (ESI). The method had a chromatographic run time of 12.0
      min and a linear calibration curve over the concentration range of 1.0-800 ng/ml
      for pseudoephedrine and 1.0-400 ng/ml for cetirizine, respectively. The lower
      limit of quantification of the two drugs was 1.0 ng/ml, respectively. The intra-
      and inter-batch precisions were less than 9.7%. The method described herein has
      been first used to reveal the pharmacokinetic characters in healthy Chinese
      volunteers treated with oral administration of different dosages of cetirizine
      dihydrochloride and controlled-released pseudoephedrine hydrochloride compound
      tablet, and approached the influence of a standard meal on the extent and rate of
      absorption of the combination tablet.

PMID- 16971195
TI  - Simple and sensitive determination of Delta(9)-tetrahydrocannabinol, cannabidiol
      and cannabinol in hair by combined silylation, headspace solid phase
      microextraction and gas chromatography-mass spectrometry.
AB  - A new method for determination of Delta(9)-tetrahydrocannabinol (THC),
      cannabidiol (CBD) and cannabinol (CBN) in hair based on alkaline hair hydrolysis,
      extraction by iso-octane, combined derivatization with N,O-bis-(trimethylsilyl)
      trifluoroacetamide and headspace solid phase microextraction of the extract
      residue, and gas chromatography-mass spectrometry was developed and evaluated.
      The limits of detection of the three compounds were 0.01-0.02 ng/mg. The method
      was routinely applied to more than 250 hair samples. In 77 positive samples, the
      concentrations ranged from LOD to 4.2 ng/mg for THC (mean 0.49 ng/mg), to 12.1
      ng/mg for CBD (mean 0.37 ng/mg) and to 0.85 ng/mg for CBN (mean 0.12 ng/mg) using
      a sample amount of 30 mg. The frequently observed increase of the segmental drug
      concentrations from proximal to distal is explained by progressive accumulation
      in the hair shaft from sebum or side stream smoke.

PMID- 16971196
TI  - Synchronous gastric and colonic MALT-lymphoma in coeliac disease: a long-term
      follow-up on gluten-free diet.
AB  - We describe the first case of synchronous gastric and colonic mucosa-associated
      lymphoid tissue lymphoma in coeliac disease. After refusing any other treatment,
      the patient started a gluten-free diet but a re-evaluation 3 years later failed
      to demonstrate improvement of the gastric neoplasia on a gluten-free diet, whilst
      the colonic mucosa-associated lymphoid tissue lymphoma behaviour was unknown (the
      patient refused a new colonoscopic evaluation).

PMID- 16971198
TI  - A new world.

PMID- 16971197
TI  - CYP17 and COMT gene polymorphisms can influence bone directly, or indirectly
      through their effects on endogenous sex steroids, in postmenopausal Japanese
      women.
AB  - We aimed to assess whether circulating sex steroids would influence bone density
      and bone loss, whether part of this influence could be explained by genetic
      variation measured as polymorphisms in candidate genes affecting circulating
      hormone levels, or whether gene polymorphisms would have direct effects on bone
      in 229 postmenopausal Japanese women aged 46 years and over who had been followed
      for eight years (Yokohama Cohort). Bone mineral density (BMD) in the lumbar spine
      (L), femoral neck (FN), total hip (T) and distal radius (R) was measured every
      year, and endogenous sex steroid levels were determined at the start of the
      study. We investigated the polymorphisms of estrogen-metabolizing enzyme gene,
      CYP17; estrogen biosynthesis (high activity, A2/A2), CYP1A1; hydroxylation (high
      inducibility, vt/vt) and COMT; inactivation (low activity, L/L) with PCR-based
      restriction fragment length polymorphism assays. Dehydroepiandrosterone (DHEA)
      and androstenedione (AND) levels significantly correlated with bone density in
      both the axial (L) and the appendicular skeleton (FN, T and R) (r=0.194-0.229;
      P<0.05) whereas estradiol (E2) and AND showed significant correlations with bone
      change only at the axial skeleton (r=0.205 and r=-0.139, respectively; P<0.05) on
      the total cohort. These correlations remained significant in thin/normal-weight
      women [body mass index (BMI) <25 kg/m2)] even after adjustment for years since
      menopause (YSM) and BMI or age and BMI, suggesting an interaction of BMI and sex
      steroid/BMD association. On the total cohort, a difference in endogenous DHEA
      levels between CYP17 homozygote A2 and non-homozygote A2; an increasing trend in
      AND levels from COMT L/L, L/H, to H/H; and a difference in TS level between COMT
      homozygote L and non-homozygote L were separately observed. All observations were
      significant for unadjusted and adjusted analysis, except for COMT and TS. In
      thin/normal-weight women (BMI <25 kg/m2), the same effects of CYP17 genotypes on
      DHEA were observed as on the total cohort. CYP17 and COMT genes showed some
      direct influence on bone density. Mean percent change in T-BMD was negative for
      CYP17 non-homozygote A2 in contrast to a positive value for homozygote A2. Mean
      percent change in R-BMD showed the difference between COMT homozygote L and non
      homozygote L with a larger decrease for the homozygote L. Together, CYP17 and
      COMT genotypes might have some effect on bone both directly and indirectly
      through their effects on endogenous sex steroids in postmenopausal Japanese
      women.

PMID- 16971199
TI  - Novel techniques in hernia repair.

PMID- 16971200
TI  - Effects of recombinant activated factor VII in traumatic nonsurgical intracranial
      hemorrhage.
AB  - OBJECTIVE: To determine whether treatment with recombinant activated factor VII
      (rFVIIa) will prevent progression of bleeding in nonsurgical hemorrhagic
      traumatic brain injury (TBI). METHODS: Chart review from the trauma registry of a
      level 1 trauma center between January 1, 2002 and December 31, 2004 identified 2
      patients who received rFVIIa for progressive hemorrhagic TBI. These patients were
      given a single dose of rFVIIa (120 mcg/kg) after a repeat head computed
      tomography (CT) scan showed worsening of intracranial bleeding. Pre-rFVIIa and
      post-rFVIIa coagulation parameters and postintervention CT scans were performed.
      A matched convenience sample was drawn from the institution's trauma registry
      reflecting similar injury patterns. RESULTS: The 2 patients who received rFVIIa
      were ages 61 and 79 years; the patients in the matched convenience sample were 57
      and 63 years. Both sets of patients comprised 1 man and 1 woman who had suffered
      blunt trauma, including hemorrhagic TBI, and were matched according to age,
      gender, and injury severity score (ISS). During their hospital course, repeat CT
      scans documented worsening of intracranial hemorrhage in both cohorts. In the
      rFVIIa patients, follow-up CT showed overall improvement of head injury compared
      with the convenience sample. The rFVIIa patients also saw an appreciable decrease
      in both prothrombin time (PT) and international normalized ratio (INR).
      CONCLUSIONS: In hemorrhagic TBI, rFVIIa has the potential to limit or even halt
      the progression of bleeding that would otherwise place growing pressure on the
      brain. A prospective, randomized multicenter trial is planned to elucidate this
      hypothesis.

PMID- 16971201
TI  - Right lower quadrant pain in a young adult male.

PMID- 16971202
TI  - Intestinal fatty acid binding protein (I-FABP) for the detection of strangulated
      mechanical small bowel obstruction.
AB  - OBJECTIVE: Intestinal fatty acid binding protein (I-FABP), a protein released by
      necrotic enterocytes, is a useful marker for the detection of ischemia from
      mechanical small bowel obstruction. DESIGN: Validation cohort. SETTING: Academic
      medical center. PARTICIPANTS: Cohort of 21 patients admitted with a clinical
      diagnosis of mechanical small bowel obstruction. Plasma and urine samples were
      collected from patients upon hospital admission and again immediately before
      laparotomy if surgical intervention was delayed. RESULTS: Plasma and urine I-FABP
      levels (pg/ml by enzyme-linked immunosorbent assay) in patients found to have
      small bowel necrosis at the time of laparotomy were compared with those without
      significant ischemia upon laparotomy and those that did not require laparotomy
      and, by default, did not have small bowel ischemia. A positive test was defined
      as 1000-pg/ml I-FABP in urine and 100-pg/ml I-FABP in plasma. Small bowel
      necrosis was confirmed in 3 of 21 enrolled patients. Urine I-FABP levels were
      positive in 3 of 3 patients with necrosis and 3 of 18 patients without necrosis
      (sensitivity 100%, specificity 83%, PPV 50%, NPV 100%). Plasma I-FABP levels were
      positive in 3 of 3 patients with necrosis and 4 of 18 patients without necrosis
      (sensitivity 100%, specificity 78%, PPV 43%, NPV 100%). CONCLUSIONS: I-FABP is a
      sensitive marker for ischemia in mechanical small bowel obstruction. Additional
      work should be done to validate I-FABP in a variety of clinical settings and to
      develop a rapid I-FABP laboratory assay.

PMID- 16971203
TI  - The risk of carotid endarterectomy in patients with chronic renal insufficiency.
AB  - OBJECTIVE: Carotid endarterectomy (CEA) has been associated with less favorable
      outcome in patients with chronic renal insufficiency (CRI). The authors compared
      results of CEA in the presence and absence of CRI at their institution over a 5
      year period. DESIGN/SETTING/PARTICIPANTS: This article is a retrospective review
      of 1351 patients who underwent CEA between 1998 and 2004. Chronic renal
      insufficiency was present in 143 patients. Renal insufficiency was graded as mild
      (creatinine 1.6-2.9 mg/dL) or severe (creatinine > or = 3.0 mg/dL or on
      hemodialysis). The composite endpoint was stroke or death within 30 days
      postoperatively. The results were compared with 150 consecutive patients having
      CEA in the absence of renal insufficiency between 2002 and 2003. RESULTS: For the
      143 patients with CRI, the composite endpoint was 9.0%, whereas the composite
      endpoint for the 150 control patients without CRI was 2.6% (p = 0.032). For
      patients with severe CRI (creatinine > or = 3.0 or on hemodialysis), the
      composite endpoint was 19.0% (p = 0.08). For those with mild CRI (creatinine 1.6
      2.9), the composite endpoint was 7.3% (p = 0.06). CONCLUSIONS: Chronic renal
      insufficiency is associated with increased incidence of stroke, myocardial
      infarction, and death after CEA. For patients with advanced CRI, carotid artery
      stenting (CAS) or aggressive medical management may be alternative treatment
      options.

PMID- 16971204
TI  - Adenocarcinoma of the distal pancreas presenting as an intrathoracic mass.
AB  - Tumors of the pancreatic head may present with early heralding symptoms such as
      obstructive jaundice. Pancreatic masses within the body or tail usually have
      delayed diagnosis secondary to the lack of any early findings, which, in turn,
      leads to a higher incidence of involvement of adjacent structures, such as the
      superior mesenteric artery, portal vein, or superior mesenteric vein. Local
      involvement along with distant metastases or larger tumor size may be
      contraindications to surgical resection. The authors report a case of advanced
      pancreatic adenocarcinoma in which the anomalous thoracic location of the organ
      resulted in the tumor being resectable. This case adds support to an aggressive
      approach to surgical resection of distal pancreatic tumors.

PMID- 16971205
TI  - Bowel perforation from bevacizumab for the treatment of metastatic colon cancer:
      incidence, etiology, and management.
AB  - Avastin (Bevacizumab) is a recently developed monoclonal antibody against
      vascular endothelial growth factor (VEGF) receptor that increases survival in
      patients with metastatic colorectal cancer. Bowel perforation is a known risk
      factor of unknown etiology associated with the use of Avastin. In this report,
      the incidence, risk factors, typical presentation, and management of patients
      with this complication is described.

PMID- 16971206
TI  - Lipomatous disorder of the peri-trochanteric soft tissue: case report and review.
AB  - Disorders of fatty tissue metabolism and body contour are frequently described in
      the literature. Several different syndromes have been ascribed to recurring
      characteristics of fatty deposition with similar underlying etiologies. These
      syndromes can generally be classified into the lipomatoses (abnormal
      accumulations of fat) and the lipodystrophies (abnormal fat atrophy). The authors
      describe a case of isolated symmetrical lipomatosis of the soft tissue overlying
      the trochanters that developed a recurrence after treatment with liposuction.
      They have attempted to match this patient's disorder into 1 of several reported
      syndromes, with benign symmetric lipomatosis and acquired partial lipodystrophy
      at the top of the differential diagnosis. However, some characteristics of this
      patient may warrant a separate categorization for her condition. In this case
      report, the current literature on disorders of fatty tissue metabolism is
      reviewed and a discussion of relevant factors and issues surrounding their
      clinical significance and management is provided.

PMID- 16971207
TI  - Littoral cell angioma: a case report and review.

PMID- 16971208
TI  - Spontaneous pneumomediastinum.

PMID- 16971209
TI  - Preparing for the in-training service examination.

PMID- 16971210
TI  - Preparing for the in-service examination.

PMID- 16971211
TI  - The challenges of patient advocacy on the wards: reflections from a third-year
      medical student.

PMID- 16971212
TI  - Delivering value-added results: one program's perspective.

PMID- 16971213
TI  - The importance of a highly active and DeltapH-regulated diatoxanthin epoxidase
      for the regulation of the PS II antenna function in diadinoxanthin cycle
      containing algae.
AB  - The present study focuses on the regulation of diatoxanthin (Dtx) epoxidation in
      the diadinoxanthin (Ddx) cycle containing algae Phaeodactylum tricornutum,
      Thalassiosira pseudonana, Cyclotella meneghiniana and Prymnesium parvum and its
      significance for the control of the photosystem II (PS II) antenna function. Our
      data show that Dtx epoxidase can exhibit extremely high activities when algal
      cells are transferred from high light (HL) to low light (LL). Under HL
      conditions, Dtx epoxidation is strongly inhibited by the light-driven proton
      gradient. Uncoupling of the cells during HL illumination restores the high
      epoxidation rates observed during LL. In Ddx cycle containing algae, non
      photochemical quenching of chlorophyll fluorescence (NPQ) is directly correlated
      with the Dtx concentration and independent of the presence of the proton
      gradient. This means that a fast conversion of PS II from the heat dissipating
      state back to the light-harvesting state can only be realized by an efficient
      removal of the quenching pigment Dtx. It is proposed that the high Dtx
      epoxidation rates during LL illumination serve exactly this purpose. The
      inhibition of Dtx epoxidation by the DeltapH, on the other hand, ensures rapid
      increases in the Dtx concentration when photoprotection under conditions of HL
      illumination is required. The regulation of the PS II antenna function in Ddx
      cycle containing algae is different to that in violaxanthin (Vx) cycle containing
      plants, where for the zeaxanthin (Zx)-dependent NPQ the presence of a proton
      gradient is mandatory. In the green alga Chlorella vulgaris conversion of PS II
      from the heat dissipating state back to the light-harvesting state is controlled
      by the DeltapH, whose relaxation after a transition from HL to darkness or LL
      rapidly abolishes the thermal dissipation of excitation energy, including the Zx
      dependent NPQ. Due to the inability of Zx to quench fluorescence in the absence
      of the DeltapH a fast epoxidation of Zx to Vx in LL is not needed and is missing
      in Chlorella vulgaris.

PMID- 16971214
TI  - Effects of NaCl on the growth, ion accumulation and photosynthetic parameters of
      Thellungiella halophila.
AB  - Thellungiella halophila seedlings grown on a solid substrate for 25 days on
      standard medium were challenged with NaCl. Growth, tissue hydration, ion
      accumulation, photosynthesis, lipid peroxidation and antioxidant enzymatic
      activities were studied on rosette leaves. Three accessions of Arabidopsis
      thaliana were cultivated under the same conditions. During the first two weeks of
      salt treatment, the growth of T. halophila leaves was restricted by NaCl. No
      significant difference appeared between T. halophila and A. thaliana concerning
      biomass deposition, or hydric and ionic parameters. However, all A. thaliana
      plants displayed foliar damage, and died during the third week of salt (50mM
      NaCl) treatment. Almost all (94%) T. halophila plants remained alive, but did not
      display any sign of altered physiological condition. Tissue hydration,
      chlorophyll content, stomatal conductance, photosynthetic quantum yield, and
      photosynthetic rate were very similar to those of control plants. Lipid
      peroxidation, estimated from thermoluminescence, was very low and insensitive to
      salt treatment. Only slight changes occurred in antioxidant enzymatic activities
      (SOD, several peroxidases, and catalase). From the absence of physiological
      disorder symptoms, we infer that salt was efficiently compartmentalized in leaf
      vacuoles. In salt-treated A. thaliana, the photosynthetic quantum yield was
      diminished, and lipid peroxidation was augmented. These observations reinforce
      the conclusion that T. halophila could accumulate salt in its leaves without
      damage, in contrast to A. thaliana.

PMID- 16971215
TI  - Physiological and biochemical responses resulting from nitrite accumulation in
      tomato (Lycopersicon esculentum Mill. cv. Ibiza F1).
AB  - The sensitivity of hydroponically cultivated tomato (Lycopersicon esculentum
      Mill. cv. Ibiza F1) submitted to nitrite treatments (0.25-10mM KNO(2)) for 7d was
      studied. Increasing nitrite levels in the culture medium led to several
      disruptions of tomato plants, reflected by reductions of both dry matter per
      plant, chlorophyll concentrations and the appearance of chlorosis symptoms at the
      leaf surface. This behaviour was accompanied by stimulation of nitrite, nitrate
      and ammonia ion accumulation, mainly in roots and old leaves. Higher proteolytic
      and gaiacol peroxidase (GPX, EC. 1.11.1.7) activities and malonyldialdehyde
      content were also noted. Protein content of the different plant organs was
      decreased by nitrite treatment. These physiological and biochemical parameters
      were chosen as they are stress indicators. Taken together, our data partly
      explain the harmful effects of nitrite ions, when excessive in the culture
      medium.

PMID- 16971216
TI  - Induction of an anionic peroxidase in cowpea leaves by exogenous salicylic acid.
AB  - Two isoperoxidases were detected in cowpea (Vigna unguiculata) leaves. Treatment
      of the primary leaves with 10mM salicylic acid increased the total peroxidase
      activity contributed by the anionic isoform. To isolate both the anionic and
      cationic peroxidases the leaf crude extract was loaded on a Superose 12 HR 10/30
      column followed by chromatography on Mono-Q HR 5/5. Both enzymes were stable in a
      pH range from 5 to 7. The optimum-temperatures for the cationic and anionic
      peroxidase isoforms were, respectively, 20-30 degrees C and 30 degrees C. The
      dependence of guaiacol oxidation rate varying its concentration at constant
      H(2)O(2) concentration showed, for both enzymes, Michaelis-Menten-type kinetic.
      Apparent K(m)(s) were 0.8 and 4.8 microM for the cationic and anionic
      isoperoxidases, respectively.

PMID- 16971217
TI  - Assessment of genetic and epigenetic variation in hop plants regenerated from
      sequential subcultures of organogenic calli.
AB  - Organogenic calli induced from internodal segments were subcultured three times.
      Regenerated plants obtained from each subculture were analysed by molecular
      methods. No major genetic rearrangements were detected in the callus-derived
      plants since none of the amplified fragment-length polymorphism (AFLP) loci were
      found to be polymorphic. However, epigenetic changes due to a demethylation
      process were detected by methylation-sensitive amplified polymorphism (MSAP)
      technique. The results allowed inference of the possible relationship among the
      plants derived from different calli subcultures and the in vitro control. The
      plants recovered from the first and second callus subcultures clustered with the
      in vitro control pools in the phenogram while the regenerants from the third
      callus subculture showed the highest genetic distance with the controls. This is
      the first study reporting data about the genetic stability of callus-derived
      Humulus lupulus L. plants.

PMID- 16971218
TI  - A thin phenotype is protective for impaired glucose tolerance and related to low
      birth weight in mice.
AB  - BACKGROUND: Low birth weight is an independent risk factor for impaired glucose
      tolerance (IGT) and diabetes in adult life. This risk extends to both preterm and
      term infants, a particularly important finding given the increased survival of
      low-birth-weight infants with improvements in neonatal care. One potential
      strategy for prevention of low-birth-weight-associated glucose intolerance is
      postnatal nutritional modification and prevention of early postnatal weight gain.
      To determine the efficacy of this approach, we utilized our mouse model of low
      birth weight related to maternal undernutrition during the third week of
      pregnancy. METHODS: We studied three experimental groups of offspring mice:
      controls (C), undernutrition with low birth weight (UN) fed ad lib postnatally,
      and undernutrition with food restriction continued in postnatal life (UN-UN).
      Mean birth weight was significantly reduced in both groups of undernutrition
      offspring in utero (C: 1.86 +/- 0.03 vs. UN: 1.37 +/- 0.04 and UN-UN: 1.32 +/-
      0.06, p <0.001). As expected, and in accord with human data, differences in
      weight between C and UN mice disappeared by week 2 of life, indicating catch-up
      growth in the UN group. RESULTS: Body weight was similar in all groups until 4
      months of age, after which the UN-UN group had reduced body weight as compared
      with controls (p <0.05 at 6 months). Insulin tolerance test (1 U/kg), glucose
      tolerance test (2 g/kg) and glucose-stimulated insulin secretion test (3 g/kg) at
      2 months of age were identical among C, UN, and UN-UN groups. By age 6 months,
      IGT had developed in the UN mice (p <0.05 vs. C). By contrast, UN offspring with
      caloric restriction postnatally (UN-UN) were protected from the development of
      glucose intolerance, with glucose levels identical to that of control mice. These
      differences appeared to be related to improved insulin sensitivity in the UN-UN
      mice as compared with UN mice, although data did not reach statistical
      significance. CONCLUSIONS: Our data suggest that alterations in early postnatal
      nutrition are associated with prevention of weight gain and the development of
      IGT in low-birth-weight mice.

PMID- 16971219
TI  - Influence of electromagnetic fields and protective effect of CAPE on bone mineral
      density in rats.
AB  - BACKGROUND: Most mobile phones emit electromagnetic radiation at 900 MHz or 1800
      MHz. An electromagnetic field has some biological effects on the behavior of the
      cell population of bone. The aim of this work is to evaluate the effects of the
      radiation emitted by mobile phones on bone mineral density (BMD). The effects of
      caffeic acid phenethyl ester (CAPE) on the radiation-induced changes were also
      investigated. METHODS: In the study, 48 Sprague Dawley rats were used. Rats were
      divided into five groups as follows: control, irradiated with 900 MHz, irradiated
      with 900 MHz and treatment, irradiated with 1800 MHz, irradiated with 1800 MHz
      and treatment groups. The rats in the control group (first group) were left
      within the experimental setup during 30 min/day for 28 days without radiation
      exposure. Nine hundred-MHz radiation group was exposed to irradiate both second
      and third groups for 28 days (30 min/day); 1800-MHz radiation group was exposed
      to irradiate both fourth and fifth groups for 28 days (30 min/day). Third and
      fifth groups were also treated by CAPE for 28 days. Treatment groups received 10
      microml/kg/day CAPE i.p. before the irradiation. Bone mineral densities were
      determined in all groups. RESULTS: BMD was found to be decreased in the
      irradiated groups and to be increased in the treatment groups. CONCLUSIONS: The
      changes were not significant (p >0.05).

PMID- 16971220
TI  - Resveratrol improves ischemia/reperfusion-induced oxidative renal injury in rats.
AB  - BACKGROUND: The present study was designed to examine whether resveratrol, a
      potent antioxidant, protects against renal ischemia-reperfusion (I/R) injury.
      METHODS: Wistar albino rats were unilaterally nephrectomized and subjected to 45
      min of renal pedicle occlusion followed by 6 h of reperfusion. Resveratrol (RVT,
      30 mg/kg, i.p.) or vehicle was administered twice, at 30 min prior to ischemia
      and immediately before the reperfusion period. At the end of the reperfusion
      period, rats were decapitated and kidney samples were taken for histological
      examination or determination of levels of renal malondialdehyde (MDA), an end
      product of lipid peroxidation; glutathione (GSH), a key antioxidant; and
      myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration.
      Formation of reactive oxygen species in hepatic tissue samples was monitored by
      using chemiluminescence (CL) technique with luminol and lucigenin probes. Renal
      tissue collagen content as a fibrosis marker was also determined, while serum
      creatinine and urea concentrations were measured for the evaluation of renal
      function. Tumor necrosis factor-alpha (TNF-alpha ) and lactate dehydrogenase
      (LDH) were also assayed in serum samples. RESULTS: Ischemia/reperfusion caused a
      significant decrease in tissue GSH level, which was accompanied by significant
      increases in the renal luminol and lucigenin CL values, MDA level, MPO activity
      and collagen content. Similarly, serum creatinine and BUN levels, as well as LDH
      and TNF-alpha, were elevated in the I/R group as compared to control group. On
      the other hand, resveratrol treatment reversed all these biochemical indices, as
      well as histopathological alterations that were induced by I/R. CONCLUSIONS:
      Findings of the present study suggest that resveratrol exerts renoprotective
      effects via its radical scavenging and antioxidant activities, which appear to
      involve the inhibition of tissue neutrophil infiltration.

PMID- 16971221
TI  - Microscopic characterization of follicular structures in letrozole-induced
      polycystic ovarian syndrome in the rat.
AB  - BACKGROUND: Our objective was to characterize the tissular distribution of
      relevant cytoskeletal proteins, cellular adhesion molecules and proliferation
      markers and conduct a histomorphometrical study of the follicular wall of
      letrozole-induced polycystic ovaries. METHODS: Twenty rats were divided into two
      groups: a control group (C) of ten rats that received vehicle only (0.9% NaCl
      solution) once daily p.o. and a treatment group (T) of ten animals administered
      letrozole at a concentration of 1 mg/kg p.o. dissolved in 0.9% NaCl solution once
      daily during 21 days. Twenty four h after the last administration, all animals
      were sacrificed. Control animals were sacrificed in proestrous (n = 5) and
      diestrous (n = 5). Serum hormone levels, histomorphometrical changes and
      immunoexpression of intermediate filaments (vimentin, cytokeratins and desmin),
      cadherins and proliferation cellular nuclear antigen were examined. RESULTS: The
      granulosa cell layer of cystic follicles had a greater significant immunostaining
      for vimentin and cytokeratins. Immunohistochemical localization of desmin was
      restricted to the theca externa. Positive immunoreactivity for cadherins rises
      gradually and significantly, together with the follicular development, and
      immunoreactivity was comparatively stronger in follicular cysts. A significantly
      higher immunostaining for PCNA cells was observed in secondary and tertiary
      follicles as compared with atretic and cystic follicles. An increase in the LH,
      FSH and testosterone serum concentrations was observed in letrozole-treated rats.
      Estradiol and progesterone showed a considerable reduction. CONCLUSIONS: The
      changes observed are probably due to structural and functional alterations that
      occur during the process of cystogenesis and may be associated with important
      modifications in the expression of cytoskeletal proteins, cellular adhesion
      molecules and proliferation markers that may be essential for proper cellular
      functioning.

PMID- 16971222
TI  - Effects of electromagnetic radiation from a cellular phone on human sperm
      motility: an in vitro study.
AB  - BACKGROUND: There has been growing public concern on the effects of
      electromagnetic radiation (EMR) emitted by cellular phones on human health. Many
      studies have recently been published on this topic. However, possible
      consequences of the cellular phone usage on human sperm parameters have not been
      investigated adequately. METHODS: A total number of 27 males were enrolled in the
      study. The semen sample obtained from each participant was divided equally into
      two parts. One of the specimens was exposed to EMR emitted by an activated 900
      MHz cellular phone, whereas the other was not. The concentration and motility of
      the specimens were compared to analyze the effects of EMR. Assessment of sperm
      movement in all specimens was performed using four criteria: (A) rapid
      progressive, (B) slow progressive, (C) nonprogressive, (D) no motility. RESULTS:
      Statistically significant changes were observed in the rapid progressive, slow
      progressive and no-motility categories of sperm movement. EMR exposure caused a
      subtle decrease in the rapid progressive and slow progressive sperm movement. It
      also caused an increase in the no-motility category of sperm movement. There was
      no statistically significant difference in the sperm concentration between two
      groups. CONCLUSIONS: These data suggest that EMR emitted by cellular phone
      influences human sperm motility. In addition to these acute adverse effects of
      EMR on sperm motility, long-term EMR exposure may lead to behavioral or
      structural changes of the male germ cell. These effects may be observed later in
      life, and they are to be investigated more seriously.

PMID- 16971223
TI  - ABH histo-blood group antigens in human thymus involution.
AB  - BACKGROUND: Human histo-blood group antigens (HBGA) are genetically determined
      glycoproteins supposed to participate in cell differentiation, adhesion, cancer
      metastasis and angiogenesis. In tissues, HBGA are mostly expressed in epithelial
      cells (EC). The EC comprising the thymocyte microenvironment play an important
      role in the ontogeny of the thymus. The aim of the present work is to investigate
      ABH HBGA in senile thymus and to characterize their expression pattern related to
      the process of aging. METHODS: Routine histology and immunohistochemical
      techniques were applied on thymus glands from senile and young individuals.
      RESULTS: Involuted thymus exhibited large areas of adipose tissue containing
      scattered EC, all positive for HBGA. Stromal EC revealed different morphology and
      intrathymic localization but uniform cytoplasmic staining for ABH antigens.
      Endothelial cells of blood vessels and red blood cells were intensely stained for
      HBGA. Only single scattered lymphocytes possessed HBGA. In contrast with senile
      thymus, most lymphocyte populations in the gland of young individuals, as well as
      the Hassall's corpuscules, expressed HBGA. CONCLUSIONS: The epithelial framework
      reorganization during age-related thymus involution involves modulation in ABH
      antigen expression in EC. These molecules are required by thymic EC to maintain
      the reduced but important crosstalk with lymphocytes during involution. The
      diminished reactivity for ABH antigens in the lymphocytes of aged thymus might
      reflect the impaired communication between these two cell types. We present novel
      evidence for permanent presence and modulation of ABH antigen reactivity in
      senile thymus, supporting the view that these molecules might be developmentally
      regulated.

PMID- 16971224
TI  - Tumoral cell mtDNA approximately 8.9 kb deletion is more common than other
      deletions in gastric cancer.
AB  - BACKGROUND: The aim of the study was to clarify the role of deletion of
      mitochondrial DNA (mtDNA) in gastric carcinogenesis and to determine prevalence
      of mitochondrial deletions in different regions of tumoral tissue in comparison
      with adjacent non-tumoral tissue in gastric cancer. METHODS: In order to
      investigate whether a high incidence of mutations exists in mtDNA of gastric
      cancer tissues, we screened five regions of the mitochondrial genome by PCR
      amplification, Southern blot and DNA sequence analysis. RESULTS: Of 71 cancer
      patients, the approximately 8.9 kb deletion was detected among different
      deletions in 9 cases (12.67%) of the tumoral tissues and 1 case (1.40%) in non
      tumoral tissues that were adjacent to the tumors. Level of the 8.9 kb deletion
      has been found to be more than other deletions in tumoral tissues. CONCLUSIONS:
      The approximately 8.9 kb deletion has an obvious correlation with age and
      histological type. These data suggest that the approximately 8.9 kb deletion in
      mtDNA may play an important role in gastric carcinogenesis.

PMID- 16971225
TI  - Leptin receptor Lys656Asn polymorphism is associated with decreased leptin
      response and weight loss secondary to a lifestyle modification in obese patients.
AB  - BACKGROUND: Human obesity is characterized by high levels of leptin, and it has
      been suggested that obese patients may be leptin resistant. The aim of our study
      was to investigate the influence of Lys656Asn polymorphism in the leptin receptor
      gene on leptin response and weight loss secondary to a lifestyle modification
      (Mediterranean hypocaloric diet and exercise) in obese patients. METHODS: A
      population of 67 obese (body mass index >30) nondiabetic outpatients was analyzed
      in a prospective way. Before and after 3 months of lifestyle modification
      program, bipolar electrical bioimpedance, blood pressure, and a serial assessment
      of nutritional intake with 3 days written food records and biochemical analysis
      were performed. The lifestyle modification program consisted of a hypocaloric
      diet (1520 kcal, 52% carbohydrates, 25% lipids and 23% proteins). The exercise
      program consisted of aerobic exercise for at least three times per week (60 min
      each). Statistical analysis was performed for the combined Lys656/Asn656 and
      Asn656/Asn656 as mutant group and type Lys656/Lys 656 as wild-type second group.
      RESULTS: Sixty seven patients gave informed consent and were enrolled in the
      study. The mean age was 45.7 +/- 16.6 years and the mean BMI 34.1 +/- 5.1, with
      18 males (26.9%) and 49 females (73.1%). Thirty six patients (10 males/26
      females) (46.8%) had the genotype Lys656/Lys 656 (wild-type group) and 31
      patients (8 males/23 females) (46.3%) Lys656/Asn656 (n = 28, 41.8%) or
      Asn656/Asn656 (n = 3, 4.5%) (mutant group). The percentage of responders (weight
      loss) was similar in both groups (91.7 vs. 87.1%). In wild-type group (responders
      and nonresponders), BMI, weight, fat mass, systolic blood pressure and waist
      circumference decreased. In mutant group, BMI, weight and waist circumference
      decreased. No differences were detected between basal values in both groups. Only
      leptin levels decreased significantly in wild-type group (11.5%; p <0.05) (57.3
      +/- 31.5 ng/mL vs. 45.8 +/- 29.3 ng/mL; p <0.05). In mutant group, leptin
      increased without statistical differences (0.44%; ns). CONCLUSIONS: Patients with
      Asn656 allele of LEPR gene have a different response than wild-type patients, and
      Lys656Lys patients have a significant decrease in weight, BMI, fat mass, waist
      circumference, systolic blood pressure and leptin levels.

PMID- 16971226
TI  - 5-fluorouracil and weekly oxaliplatin combined with radiotherapy for locally
      advanced rectal cancer: surgical complications and long-term results.
AB  - BACKGROUND: We undertook this study to evaluate early surgical complications and
      long-term results after preoperative radiotherapy and chemotherapy (RCT) using 5
      fluorouracil (5-FU) and oxaliplatin (OXA) for rectal cancer. METHODS: Forty six
      TNM stage II-III rectal cancer patients were studied, who were given preoperative
      RT (50.4 Gy/28 fractions) combined with 5-FU (200-225 mg/m(2)/day by continuous
      venous infusion) and weekly OXA (25-60 mg/m(2)). Major complications and
      reoperations were recorded overall, whereas outcome analyses were performed only
      for patients who received the recommended regimen dosage. RESULTS: Forty three
      patients (M:F, 25:18; median age 59 years) were available for analysis. All
      patients received the planned RT dose. There were no postoperative deaths; seven
      patients had early major surgical complications, four requiring re-operation. One
      additional patient had a second surgical procedure due to a duodenal fistula
      complicating the resection of an aortic aneurysm performed concomitantly with
      rectal cancer surgery. At a median follow-up of 49 months, two of the 23 patients
      treated at the recommended doses developed recurrence (one local, and one local
      and distant), and two died of cancer progression. Following the Kaplan-Meier
      method, the estimated 5-year overall and disease-free survival rates were 92 and
      89%, respectively. CONCLUSIONS: The preoperative RCT regimen used in the present
      study incurs a low rate of recurrence with an acceptable surgical morbidity.

PMID- 16971227
TI  - Association of moderate alpha-1 antitrypsin deficiency with lung cancer in the
      Serbian population.
AB  - BACKGROUND: Alpha-1 antitrypsin (AAT) is an important serine protease inhibitor
      in human plasma. Its major physiological role is to inhibit neutrophil elastase
      (NE) in the lower respiratory tract and protect lung tissue from destruction.
      Recent studies indicated an etiological role of NE in lung cancer development.
      The aim of this study was to investigate the association of alpha-1 antitrypsin
      deficiency (AATD) with lung cancer in patients with four different histological
      types of cancer: squamous cell carcinoma, adenocarcinomas, large cell carcinoma
      and small cell carcinoma. METHODS: Phenotyping was carried out by isoelectric
      focusing (pH 4.2-4.9). We compared the frequency of AATD phenotypes in 186 lung
      cancer patients with the value obtained in our previous study in a healthy
      Serbian population (3.7%) using the Fisher exact test. RESULTS: Allele
      frequencies in patients were Pi *M 0.9677, Pi *Z 0.0215, Pi *S 0.0081 and Pi
      *other rare 0.0027. Eleven of the 186 lung cancer patients (5.9%) were AATD
      heterozygotes with moderate deficiencies (PiMZ and PiMS). When this value was
      compared with AATD heterozygote frequency obtained in the healthy individuals
      (3.7%), the difference was close to the level of significance (p = 0.055).
      However, individuals with AATD phenotypes had a higher risk of developing
      squamous cell lung cancer then those with non-deficient AAT variants (OR = 4.51,
      95% CI = 1.66-12.29). CONCLUSIONS: Our findings provide evidence of an
      association between AAT phenotypes with moderate deficiency and squamous cell
      lung cancer.

PMID- 16971228
TI  - Costs of medical care for acute myocardial infarction attributable to tobacco
      consumption.
AB  - BACKGROUND: Tobacco consumption is the principal modifiable risk factor causally
      associated with acute myocardial infarction (AMI). AMI has been an increasing and
      important cause of death in Mexico since 1980. METHODS: To estimate the direct
      health care costs of AMI, we carried out a cost of illness (COI) analysis, using
      data derived from an expert panel consensus and from medical chart review. We
      used the smoking attributable fraction (SAF) estimates to derive costs of tobacco
      consumption. We also estimated the benefits of a "Smoke-free Workplace" tobacco
      control policy in terms of avoidable deaths and health care costs savings.
      RESULTS: We estimated an annual average costs of 6,420 US dollars and 9,216 US
      dollars for non-ST segment elevation AMI (NSTEMI) and ST segment elevation AMI
      (STEMI), respectively. The total annual health care costs estimated for incident
      AMI for the IMSS state-level division of Morelos reached 2.9 million US dollars,
      of which 1.6 million US dollars was directly attributed to tobacco consumption.
      CONCLUSIONS: Our results confirm the high costs associated with smoking and show
      the potential benefits resulting from a tobacco control policy. Our estimates are
      only applicable to social security in the state-level division of Morelos and
      more likely represent a lower boundary of the total costs of cardiovascular
      diseases attributed to tobacco, because we based the costs estimation on incident
      cases, and we did not take into consideration the costs derived from prevalent
      cases, indirect costs or other intangibles.

PMID- 16971229
TI  - Prevalence of erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficiency in
      the population of western Turkey.
AB  - BACKGROUND: Newborn G6PD deficiency screening has been recognized as an essential
      component of public health care in most developed and some Mediterranean
      countries. However, such screening is yet to be widely embraced in Turkey. The
      aim of the present study was to determine the normal values of G6PD and
      deficiency prevalence of this enzyme in different age groups of people living in
      the western region of Turkey and accordingly inform and educate about favism to
      those asymptomatic carriers who usually are not aware of their G6PD deficient
      status. METHODS: A total of 1421 clinically healthy individuals without evidence
      of leukocytosis or thrombocytosis were included in the study. Activity of G6PD
      was quantitatively measured. RESULTS: Normal mean values of G6PD in healthy males
      were 8.94 +/- 8.65 IU/g Hb (or 231.73 +/- 43.16 IU/10(12) RBC), in females were
      9.16 +/- 3.78 IU/g Hb (or 219.9 +/- 43.1 IU/10(12) RBC). The frequencies of
      severe and mild G6PD deficiencies were 0.44% and 6.07% in females, respectively,
      whereas in males it was 7.24%. Overall frequency of the G6PD-deficient phenotype
      was detected as 6.9%. CONCLUSIONS: There is no significant statistical difference
      of G6PD activity between males and females, although frequency of the G6PD
      deficient phenotype is relatively high in western Turkey. The results emphasize a
      need for screening for G6PD deficiency before prescribing anti-malarial therapy
      with drugs like primaquine to patients in this region of Turkey known for its
      prevalence of malaria.

PMID- 16971230
TI  - Prevalence of hyperuricemia and its relationship with metabolic syndrome in Thai
      adults receiving annual health exams.
AB  - BACKGROUND: Associations between hyperuricemia, metabolic syndrome,
      cardiovascular disease and diabetes have been reported. Limited information,
      however, is available concerning the prevalence and correlates of hyperuricemia
      among Thai men and women. We sought to estimate the prevalence of hyperuricemia
      among a population of patients receiving annual health exams and to evaluate its
      relationship with metabolic syndrome (MetS). METHODS: We conducted a cross
      sectional study of 1,381 patients (376 men and 1,005 women) who first
      participated in annual health examinations at the Preventive Medicine Clinic of
      the King Chulalongkorn Memorial Hospital in Bangkok, Thailand during the period
      July 1999 through February 2000. Hyperuricemia was defined as >7.0 mg/dL in men
      and >6.0 mg/dL in women. MetS was defined using the modified ATP III criteria.
      RESULTS: The overall prevalence of the hyperuricemia was 10.6%. The condition was
      more common in men than in women (18.4 vs. 7.8%). Among women, serum uric acid
      was statistically significantly correlated with body mass index (BMI), systolic
      and diastolic blood pressure, high-density lipoprotein-cholesterol, triglyceride
      and fasting plasma glucose (all p <0.05). Men with serum uric acid concentrations
      >6.7 mg/dL (upper quartile) had a 3.91-fold increased in risk of MetS (95%
      CI:1.36-11.23), as compared with those who had concentrations <5.1 mg/dL (lowest
      quartile). Among women, the risk of MetS increased at least 2-fold for
      concentration of serum uric acid concentrations >4.0 mg/dL (p for trend <0.001).
      CONCLUSIONS: Hyperuricemia is prevalent among Thai men and women receiving
      routine health exams. Additionally, serum uric acid is positively associated with
      MetS.

PMID- 16971231
TI  - Analysis of common polymorphisms in angiotensin-converting enzyme and
      apolipoprotein e genes and human longevity in Colombia.
AB  - BACKGROUND: Genetic analysis of human longevity may be useful for the
      understanding of molecular mechanisms implicated in age-related diseases. The
      molecular genetics of human longevity is largely unexplored in Latin American
      populations and other developing countries. METHODS: To explore the possibility
      of an association of common polymorphisms in two candidate genes and longevity in
      Colombia, we analyzed two polymorphisms in apolipoprotein E (APOE) and
      angiotensin-converting enzyme (ACE) genes in a sample of 538 Colombian subjects
      (18-106 years), using previously validated PCR-based methodologies. RESULTS: We
      found a significant decrease in ACE DD genotype (24 vs. 16%) between young and
      old subject groups (mean age: 45 vs. 77 years) (p = 0.03). The ACE DD genotype
      and D allele decrease was significant only in women. There were no differences
      for APOE polymorphism between young and old subjects. CONCLUSIONS: Our results
      are compatible with the expected age-related decrease of ACE DD genotype. Future
      studies examining functional single nucleotide polymorphisms (SNPs) in the ACE
      gene and its correlation with serum ACE activity in the older subjects and their
      younger relatives in this sample are warranted.

PMID- 16971232
TI  - Seroprevalence of hepatitis B and hepatitis C in patients with thalassemia and
      sickle cell anemia in a long-term follow-up.
AB  - BACKGROUND: Transfusion-dependent patients are more prone to acquiring various
      transfusion-transmitted infections such as hepatitis B (HBV), hepatitis C (HCV)
      and human immunodeficiency virus (HIV). The aim of the study was to investigate
      the prevalence of these infections in patients with thalassemia and with sickle
      cell anemia (SCA) receiving multiple blood transfusions. METHODS: The subjects of
      the present study were 399 multi-transfused patients with beta-thalassemia major
      or intermedia and SCA who have been registered at the two regional
      hemoglobinopathy centers in Turkey since 1996. Hepatitis B surface antigen
      (HBsAg), hepatitis C virus antibodies (anti-HCV) and human immunodeficiency virus
      antibodies (anti-HIV) tests were assayed by a second-generation enzyme-linked
      immunosorbent assay method. RESULTS: Of the 399 patients, 3 were HBsAg positive
      (0.75%), 18 were anti-HCV positive (4.5%), and none was anti-HIV positive. All
      patients with HBsAg and 14 (77.7 %) patients with HCV received initial blood
      transfusions before second-generation tests were performed. Patients who were
      anti-HCV positive had a significantly higher mean number of blood transfusions
      and peak serum alanine transaminase level than anti-HCV-negative patients.
      CONCLUSIONS: These results showed that after introduction of more sensitive
      screening tests and stringent donor selection procedures, incidence of HCV
      infection was significantly reduced, but there was still a serious risk for HCV
      infection, and there was a minor risk for HBV infection in patients with
      thalassemia and SCA.

PMID- 16971233
TI  - Epidemiology of adverse cutaneous drug reactions. A prospective study in
      hospitalized patients.
AB  - BACKGROUND: Drug reactions are commonly present in the skin; however, their
      frequency in our setting is unknown. METHODS: A 10-month prospective cohort study
      including all hospitalized patients was designed. Those with adverse cutaneous
      drug reactions (ACDR) were clinically identified. RESULTS: Thirty five drug
      reactions (prevalence of 0.7%) were seen among 4785 (2713 females, 2072 males)
      discharged patients. According to Begaud's imputability criteria, the reactions
      were most likely attributed to a drug in 4.87%, likely in 41.46% and possible in
      53.65%. The most commonly seen dermatoses were morbilliform rash 51.2%, urticaria
      12.2% and erythema multiforme 4.9%. Drugs most frequently associated with ACDR
      were amoxicillin clavulanate (8), amphotericin B (2) and metamizole (4).
      Expressed as risk by 1000 day-doses (Dd: the risk a patient has of developing an
      ACDR after receiving 1 day of treatment with the drug): amoxicillin clavulanate
      Dd 7.7, amphotericin B Dd 4.8 and metamizole Dd 3.7. Immunosuppressed patients
      were most frequently affected. Notably, patients with systemic lupus
      erythematosus (SLE) had a 4.68 higher risk (CI 95% 1.794-12.186 p <0.001) of
      developing an ACDR. AIDS patients showed a risk of 8.68 (CI 95% 2.18-33.19 p
      <0.001). Non-Hodgkin's lymphoma patients also had an increased risk of developing
      an ACDR. Six of the 35 identified cases were patients who had been hospitalized
      due to a severe drug reaction (1.3/1000 patients); one died from complications
      directly related to the ACDR, representing a 16.6% mortality rate among those
      admitted for an ACDR and 0.02% among the global mortality. CONCLUSIONS: We have a
      low prevalence of drug reactions compared to data reported in the literature.
      Pharmacovigilance with special attention to immunosuppressed SLE or AIDS patients
      is stressed.

PMID- 16971234
TI  - Serum ghrelin and carotid atherosclerosis in older Japanese people with metabolic
      syndrome.
AB  - Ghrelin may play a role in the development of atherosclerosis. However, the
      effect of serum ghrelin on carotid intima-media thickness (cIMT) (well
      established as a surrogate marker to atherosclerosis) in metabolic syndrome (MS),
      particularly among relatively older subjects, has still not been thoroughly
      investigated. A total of 101 subjects >60 years of age (mean age, 72.3 years)
      with MS were enrolled in the study to investigate the relationship between serum
      total ghrelin and B-mode ultrasonographic cIMT levels. There were significantly
      positive correlations between cIMT and both age and systolic BP, but cIMT was
      significantly inversely correlated to ghrelin levels. In the multiple regression
      analysis for cIMT adjusted by other measured parameters, ghrelin was a
      significant and independent factor along with age and systolic BP. These findings
      suggest that decreased ghrelin levels may be related to carotid atherosclerosis
      among older subjects with MS.

PMID- 16971235
TI  - A five-day gradual reduction regimen of chlormadinone reduces premenstrual
      anxiety and depression: a pilot study.
AB  - BACKGROUND: Anxiety and depression commonly occur in premenstrual dysphoric
      disorder (PMDD). The PMDD symptomatology disappears once the menstrual cycle
      reinitiates, resembling a withdrawal syndrome. METHODS: The present study is a
      pilot, controlled, double-blind study exploring the effectiveness of a
      premenstrual 5-day gradual reduction regimen of chlormadinone acetate on PMDD.
      Volunteers received an initial dose of 10 mg (five 2-mg tablets) on the 24(th)
      day of the menstrual cycle and one-fifth of the dose less (one tablet) each day
      until a dose of 2 mg (one 2-mg tablet) was reached on the 28(th) day of the
      menstrual cycle. The control group received placebo with a similar regimen.
      RESULTS: The 5-day gradual reduction regimen of chlormadinone significantly
      improved (F(3.76) = 3.29, p <0.02) the daily symptoms report (DSR) scores by the
      third month of treatment. The resulting relative risk was 4.09 (confidence
      interval: 1.15-14.57, p <0.005, 95% CI). Compared to placebo, chlormadinone
      clinically and statistically reduced the severity of depression, anxiety, food
      cravings, mood swings and cramps. A statistical reduction of symptoms such as
      poor coordination, irritability, feeling out of control, hopelessness, decreased
      interest and headache was detected but was not clinically relevant. No changes
      occurred in concentration difficulties, tiredness, insomnia, swelling, breast
      tenderness and aches. As side effects, 30% of the volunteers showed changes in
      the length of the menstrual cycle, and 15% experienced dyspepsia. CONCLUSIONS: A
      5-day gradual reduction regimen of chlormadinone improves some of the
      discomforting ailments associated with PMDD, namely, depression and anxiety.

PMID- 16971236
TI  - First isolation of Dysgonomonas mossii from intestinal juice of a patient with
      pancreatic cancer.
AB  - BACKGROUND: Dysgonomonas species were first designated in 2000. However, clinical
      infections due to this microorganism have rarely been described. Our aim was to
      present the first isolation of Dysgonomonas mossii from intestinal juice of a
      patient with pancreatic cancer. METHODS: Predominantly appearing grayish-white
      colonies grown on chocolate and sheep blood agar plates were characterized
      morphologically by Gram stain, biochemically by automated instrument using Vitek
      II ID-GNB card together with commercially available kit systems, ID-Test HN-20
      and API rapid ID 32A32A, and genetically by sequencing the 16S rRNA gene of the
      organism using a Taq DyeDeoxy Terminator Cycle Sequencing and a model 3100 DNA
      sequencer instrument. The isolate was further characterized by antimicrobial
      susceptibility using MicroFast 4J Panels and additional biochemical and
      physiological properties. RESULTS: The isolate was finally identified as D.
      mossii from the findings of the morphological, cultural, and biochemical
      properties together with the comparative sequence of the 16S rRNA genes. The
      isolate was highly susceptible to many antibiotics but resistant to penicillins
      and cephems. CONCLUSIONS: As D. mossii was rarely encountered in the clinical
      microbiology laboratory, it may be misidentified as an X-factor-dependent
      Haemophilus species due to its negative result for the porphyrin test.
      Accumulation of the case reports with the isolation of this species is expected
      to elucidate the infections due to D. mossii. The presence of D. mossii caused no
      significant clinical infection despite repeated isolations, as the patient had no
      conspicuous abdominal complaints. However, our report is a noteworthy and useful
      piece of information.

PMID- 16971237
TI  - Relevance of hyperbaric oxygen to ozone therapy.

PMID- 16971240
TI  - Anatomic factors and biomechanics in ankle instability.
AB  - Ankle sprains are common in both sport and leisure activities. Despite the high
      success rates of conservative management, approximately 10% to 30% patients
      develop chronic instability. Surgery yields high success rates, but clinical
      problems such as functional and mechanical instability, persistent talar tilt,
      range of motions limitations, and pain may persist despite surgery.

PMID- 16971241
TI  - Management of recurrent subluxation of the peroneal tendons.
AB  - Recurrent peroneal subluxation occurs when an acute injury is misdiagnosed or not
      adequately managed. The primary pathology is failure of the SPR, the principal
      restraint to the peroneal tendons. Several surgical techniques have been
      described. Determining the most effective technique from the small case series
      and reports in the literature is impossible. If an anatomic approach to treating
      the pathology is used, reattachment of the SPR, as we have described, seems a
      most appropriate technique. Rarely, the retinaculum in recurrent cases may not be
      robust enough to withstand repair, and a different approach to the problem may be
      required. In the future, there may be an emerging role for minimally invasive SPR
      repair with the use of endoscopic techniques.

PMID- 16971242
TI  - Diagnosis and imaging of ankle instability.
AB  - Ankle instability is a major cause of symptoms following an ankle sprain. With a
      thorough history and examination, appropriate additional investigations,
      including cross-sectional imaging, and thoughtful interpretation of the
      information, one should rarely be caught out by misdiagnosis, multiple diagnoses,
      or unusual causes.

PMID- 16971243
TI  - Acute lateral ankle sprains in track and field athletes: an expanded
      classification.
AB  - We present a longitudinal observational study on classification of acute lateral
      ankle ligament injuries in track and field athletes, based on objective criteria.
      These very common and sometimes troublesome sports injuries are treated
      functionally, but there is a lack in international literature on predicting the
      time needed for full recovery. Taking into consideration (1) active range of
      motion, (2) edema, (3) stress radiographs findings, and (4) full rehabilitation
      time, we divided grade III sprains in IIIA and IIIB, proposing that these
      injuries can be classified in four categories (I, II, IIA, IIIB). The range of
      motion-edema-stress radiographs classification that we propose evaluates the
      severity of lateral ankle injuries, is an easy and practical method, and predicts
      full return in athletic activities without residual complaints, if the proper
      rehabilitation program is executed.

PMID- 16971244
TI  - Scoring systems for evaluating ankle function.
AB  - Each of the seven systems described has advantages and drawbacks that consist of
      ease or difficulty of application, accuracy, validity, and availability. This
      article should contribute to make these systems better known and easier to apply,
      and thus, will encourage their use in clinical practice. [Fig.: see text].

PMID- 16971245
TI  - Management of acute ligament injuries of the ankle.
AB  - Ligament injuries of the ankle are common and troublesome. Management may seem
      easy, but residual symptoms ae common. Grade III injuries still generate
      controversy in terms of the best management available, and more studies are
      needed when it comes to early mobilization, cast immobilization, or surgery. Even
      the three Cohrane reviews published to date are not conclusive.

PMID- 16971246
TI  - Conservative management of chronic ankle instability.
AB  - Chronic ankle instability is a significant cause of morbidity. There are well
      documented and effective surgical options for managing this condition. However,
      conservative management can be a viable option in selected patients. Failure of
      conservative management can be an indication for surgery if morbidity warrants
      it. Surgery can be delayed without necessarily affecting outcome.

PMID- 16971247
TI  - Anatomic repair for chronic lateral ankle instability.
AB  - Symptomatic ankle instability will develop in upto 20% of patients after
      inversion injury. Although most patients can be successfully managed with
      rehabilitation and bracing, some will continue to suffer recurrent ankle
      instability with activities of daily living, work on uneven terrain, or sports.
      For this group of patients, we advocate direct anatomic surgical repair with the
      Brostrom procedure with or without its modifications.

PMID- 16971248
TI  - Operative management of ankle instability: reconstruction with open and
      percutaneous methods.
AB  - Chronic ankle instability affects a large number of young patients. A thorough
      history and clinical examination are key to proper patient selection. Once the
      patient decides to undergo operative intervention, the appropriate procedure
      should be selected according to their physical and lifestyle demands. The surgeon
      should gain familiarity with the full range of procedures, from open to
      percutaneous, and anatomic to nonanatomic. With proper patient selection,
      functional outcomes are excellent, with success rates from 80% to 90%.

PMID- 16971249
TI  - Operative management of chronic ankle instability: plantaris graft.
AB  - Precise knowledge of lateral ankle ligaments anatomy and biomechanics is
      mandatory for successful surgical reconstruction. The displayed reconstruction
      procedure fulfilled these requirements, and showed excellent clinical outcome.
      The described harvesting of the plantaris tendon at the proximal calf allows the
      use of a relatively long tendon autograft compared with the traditional
      harvesting procedure at the os calcis. Consequently, this procedure gives the
      surgeon a more efficient access to a local tendon autograft for numerous surgical
      procedures in the field of foot and ankle surgery.

PMID- 16971250
TI  - Anatomic reconstruction of the lateral ligament complex of the ankle using a
      gracilis autograft.
AB  - Many techniques have been described for surgical management of lateral ankle
      instability. Anatomic repair and nonanatomic reconstruction have higher
      recurrence rates, and may be complicated by ankle stiffness. Anatomic
      reconstruction should be considered in stabilization for deficiencies of the
      lateral ankle ligament complex, as the initial construct is stronger while
      maintaining normal ankle mechanics.

PMID- 16971251
TI  - Reconstruction of the lateral ankle ligaments with allograft in patients with
      chronic ankle instability.
AB  - The management of chronic lateral instability of the ankle remains controversial.
      In general, the anterior talofibular ligament (ATFL) must be reconstructed in all
      patients. Some will also need reconstruction of the calcaneofibular ligament
      (CFL) (or its function) to regain stability of both the ankle and the subtalar
      joints, and to avoid recurrence of instability. After reconstruction, most
      authors report good to excellent results in 80% to 85% of patients. We describe
      the augmented reconstruction technique of ATFL and CFL with a semitendinosus
      tendon allograft through a peroneal bone tunnel fixed with biodegradable anchors,
      and advocate this procedure as a safe, effective method to manage lateral ankle
      instability.

PMID- 16971252
TI  - Chronic ankle instability: management of chronic lateral ligamentous dysfunction
      and the varus tibiotalar joint.
AB  - Many techniques have been described in acute and chronic lateral ligament
      insufficiency in the ankle. At present, the Bostrom-Gould and Chrisman-Snook
      procedures and their variations remain the "gold standard". Recent assessment of
      important etiologic factors has shed some light on the relationship between the
      original injury or injuries and the subsequent development of the varus
      tibiotalar joint with or without secondary osteoarthritis. The development of
      Taylor Spatial Frame may well revolutionize its management. In the meantime,
      further consideration should be given to well-designed and evaluated randomized
      controlled trials, improved understanding of the biomechanics, and function of
      the ligaments, for example, proprioceptive function and their healing. Newer and
      less invasive arthroscopic and percutaneous techniques are being developed.

PMID- 16971253
TI  - Deltoid ligament injuries: diagnosis and management.
AB  - The medial ligaments of the ankle are injured more often than generally believed.
      Complete deltoid ligament tears are occasionally seen in association with lateral
      malleolar fractures or bimalleolar fractures. Chronic deltoid ligament
      insufficiency can be seen in several conditions, including posterior tibial
      tendon disorder, trauma- and sports-related deltoid disruptions, and valgus talar
      tilting in patients who have a history of triple arthrodesis or total ankle
      arthroplasty. This article focuses on the anatomy and function of the medial
      ligaments of the ankle and establishes a rationale for the diagnosis and
      treatment of incompetent deltoid ligament.

PMID- 16971254
TI  - Acute and chronic syndesmosis injuries: pathomechanisms, diagnosis and
      management.
AB  - Both acute and chronic syndesmotic injuries can lead to significant morbidity.
      The key to management of acute injuries is anatomic reduction of the fibula and
      the syndesmosis. A high index of suspicion for syndesmotic injuries will allow
      the surgeon to avoid the difficult reconstruction options for chronic diastasis.

PMID- 16971255
TI  - Epidemiology of sprains of the lateral ankle ligament complex.
AB  - Lateral ankle sprains account for 85% of all ankle sprains. This common injury is
      most frequently sustained during sporting activity. The ATFL is the weakest of
      the lateral ankle ligament complex, and is most frequently injured. Ankle sprains
      are often undertreated, resulting in chronic pain, muscular weakness, and
      instability. The consequence of this common injury for professional sports clubs
      is days lost in training and matches missed due to injury as well as the cost of
      rehabilitation. In the UK, an estimated 302,000 ankle sprains are seen each year
      in Accident and Emergency Departments.

PMID- 16971256
TI  - Anterior and posterior ankle impingement.
AB  - Anterior ankle impingement is characterized by anterior ankle pain on activity.
      Recurrent (hyper) dorsiflexion is often the cause. Typically, there is pain on
      palpation at the anteromedial or anterolateral joint line. Some swelling or
      limitation in dorsiflexion are present. Plain radiographs can disclose the cause
      of the impingement. In the case of spurs or osteophytes, the diagnosis is
      anterior bony impingement. In the absence of spurs or osteophytes, the diagnosis
      is anterior soft tissue impingement. In patients with anteromedial impingement,
      plain radiographs ae often falsely negative. An oblique view (anteromedial
      impingement view = AMI view) is recommended in these patients. Arthroscopic
      management with removal of the offending tissue provides good to excellent long
      term (5-8 years) results in 83% of patients with grade 0 and grade I lesions.
      Long-term results are good/excellent in 50% of patients with grade II lesions
      (osteophytes secondary to arthritis with joint space narrowing). In posterior
      ankle impingement, patients experience hindfoot pain when the ankle is forcedly
      plantarflexed. Trauma or overuse can be the cause. The trauma mechanism is
      hyperplantarflexion or a combined inversion plantarflexion injury. Overuse
      injuries typically occur in ballet dancers and downhill runners, who report pain
      on palpation at the posterolateral aspect of the talus. On plain radiographs, an
      os trigonum or hypertrophic posterior or talar process can be detected. Surgical
      management involves removal of the os trigonum, scar tissue, or hypertrophic
      posterior talar process. In the case of combined posterior bony impingement and
      flexor hallucis longus tendinopathy, a release of the flexor hallucis longus is
      performed simultaneously. Endoscopic management is associated with a low
      morbidity, a short recovery time, and provides good/excellent results at 2-5
      years follow-up in 80% of patients.

PMID- 16971258
TI  - Drug hepatotoxicity.
AB  - Drug-induced liver injury is a common but underdiagnosed cause of liver disease
      with an incidence that is rapidly increasing. The authors address some of the
      more controversial aspects in relation to drug-induced liver injury:
      recommendations on the use of anti-tuberculosis therapy in the presence of
      underlying cirrhosis, the role of periodic liver test monitoring and steroid
      therapy in relation to drug-induced liver injury, the presence of class effects
      associated with certain drugs, and the potential use of ursodeoxycholic acid in
      prolonged cholestasis.

PMID- 16971259
TI  - Alcoholic hepatitis.
AB  - Alcoholic hepatitis is a form of hepatic injury that carries a significant
      morbidity and mortality. The clinical presentation is that of fatigue, malaise,
      and jaundice in individuals who have abused excessive quantities of alcohol.
      Severity at presentation, traditionally calculated using the Maddrey Discriminant
      Function, determines outcome; the short-term mortality can be exceptionally high,
      with many persons dying within 1 month of hospitalization. This article
      summarizes the epidemiology, pathogenesis, pathology, and clinical features of
      alcoholic hepatitis. Prognostic scoring systems and therapeutic options receive
      special emphasis.

PMID- 16971260
TI  - Acute liver failure: a review.
AB  - Since publication of the first descriptions of acute liver failure (ALF) as a
      distinct clinical entity in the 1950's, the understanding of the pathophysiologic
      mechanisms involved and the management options have increased substantially. ALF
      still represents a major challenge for todays hepatologists, because it can
      rapidly lead to multiorgan failure and death that may be preventable with
      appropriate intervention. This article summarizes the basic patho-physiology
      underlying ALF, compares epidemiologic trends in the United States, the United
      Kingdom, and the Far East, and reviews prognostic markers and treatment options
      for ALF.

PMID- 16971261
TI  - Budd-Chiari syndrome.
AB  - Budd-Chiari syndrome is a spectrum of disease states, including anatomic
      abnormalities and hypercoagulable disorders, resulting in hepatic venous outflow
      occlusion. Clinical manifestations observed in the majority of patients include
      hepatomegaly, right upper quadrant pain, and abdominal ascites. This article
      outlines the approach to clinical diagnosis and supportive medical therapy in
      patients who have BCS and reviews the clinical data supporting surgical shunting
      and liver transplantation as viable treatment options in this patient population.

PMID- 16971262
TI  - Management of drug-resistant chronic hepatitis B.
AB  - Lamivudine, adefovir, and entecavir are safe and effective orally administered
      inhibitors of hepatitis B virus (HBV) replication, but drug-resistant strains of
      HBV with point mutations in the HBV polymerase gene are being reported with
      prolonged treatment that can lead to viral rebound and serum alanine
      aminotransferase flares. Salvage treatment with antiviral agents including
      investigational nucleoside/nucleotide analogues is available but highlights the
      limitations and hazards of sequential antiviral monotherapy for chronic HBV.
      Studies of pegylated interferon combined with an antiviral agent or dual
      nucleoside/nucleotide combination therapy are awaited to minimize the incidence
      of drug-resistant HBV and improve long-term outcomes.

PMID- 16971263
TI  - Hepatitis C Virus in the HIV-infected patient.
AB  - Treatment of HCV in the coinfected patient poses numerous challenges to the
      clinician: difficult comorbidities, an increased risk of medication side effects,
      and a therapy with limited response rates. End-stage liver disease from HCV has
      become a leading cause of death in coinfected patients. Without focused disease
      management, the burden of chronic liver disease in this population will rise.
      This article discusses the major trials investigating the use of interferon and
      ribavirin in coinfected patients, proposes a treatment algorithm for HCV/HIV
      coinfection, and considers approaches to patients who do not respond to this
      treatment.

PMID- 16971264
TI  - Management of hepatitis C in the setting of liver transplantation.
AB  - Each year, 5000 to 6000 liver transplantations are performed in the United
      States, 40% of which are for hepatitis C-related end-stage liver disease.
      Infection of liver allograft is universal and is associated with an accelerated
      rate of disease progression. Unfortunately, antiviral therapy after
      transplantation is less effective and often is beset with complications. This
      article reviews antiviral therapies and the factors that may influence the
      response in patients who have HCV infection both immediately before and after
      liver transplantation.

PMID- 16971265
TI  - Hepatocellular carcinoma.
AB  - The number of patients who have hepatocellular carcinoma (HCC) is expected to
      more than double over the next 1 to 2 decades. Patients who have cirrhosis,
      regardless of cause, are at the highest risk for developing HCC. This article
      discusses surveillance of these patients for HCC by alpha-fetoprotein and
      ultrasound, evaluation using imaging, classification of HCC using the Barcelona
      staging classification, and treatment. Resection, transplantation, and
      percutaneous ablation are considered curative interventions and are applied to
      about 30% of all patients who have HCC. Currently, there is no standard therapy
      for advanced HCC.

PMID- 16971266
TI  - Portal hypertension-related bleeding: management of difficult cases.
AB  - Many advances have occurred in the management of varices over the years.
      Guidelines based on sound evidence have been developed to manage the esophageal
      variceal hemorrhage. Less is known about how best to manage some of the more
      difficult cases of bleeding related to portal hypertension. This article reviews
      evidence in the hypertensive gastropathy, ectopic varices, and management of
      patients who are intolerant of or have not responded to beta-blocker therapy. The
      goal of this article is to review the sparse available evidence and to suggest
      reasonable management options.

PMID- 16971267
TI  - Hepatorenal syndrome.
AB  - Among the many causes of renal failure in patients who have advanced liver
      disease, functional renal failure occurring in the absence of parenchymal kidney
      disease, better known as hepatorenal syndrome (HRS), is the most frequent cause
      of renal dysfunction in patients who have cirrhosis. This article focuses on the
      pathogenesis, clinical features, diagnostic approach, and current treatment of
      HRS in cirrhosis.

PMID- 16971268
TI  - The diagnosis and treatment of hepatopulmonary syndrome.
AB  - Few prognostic indicators and outcomes reported for patients who have
      hepatopulmonary syndrome can be consistently reproduced between institutions. The
      lack of practice recommendations based upon consistent and predictable outcomes
      creates uncertainty for physicians trying to make the best patient choices. With
      the scarcity of donor organs, these issues are of particular importance when
      transplantation in considered as a treatment option. Much uncertainty arises from
      the basic tasks of making an accurate diagnosis in patients who have symptoms
      suggestive of hepatopulmonary syndrome. This article focuses on problems that
      underlie diagnostic accuracy and uses this information to appraise critically
      outcomes literature.

PMID- 16971269
TI  - Diagnosis and management of allograft failure.
AB  - The article focuses on diagnosis and management of allograft failure in four main
      categories: (1) ischemic-reperfusion injury (primary nonfunction), (2) technical
      complications (hepatic artery and portal vein thrombosis), (3) chronic rejection,
      and (4) recurrent disease. It also discusses the complex problems involved in
      retransplantation for allograft failure.

PMID- 16971270
TI  - Access to treatment and care associated with HIV infection among members of AIDS
      support groups in Thailand.
AB  - To examine the types and distributions of treatment received among persons living
      with HIV and AIDS (PLWHAs) in Thailand, we analyzed data collected during 2000
      from 412 members of PLWHA support organizations in Bangkok and three upcountry
      northern provinces. Most (74%) of the respondents report ever receiving modern
      medical care for their HIV-related symptoms; 31% report ever using herbal
      treatments. Small proportions of those experiencing severe symptoms related to
      activity limitations report treatments with anti-retroviral medication, treatment
      for opportunistic infections or treatment for pain. Multivariate analysis
      suggests that the government's health card system plays an important role in
      keeping treatment costs down for PLWHAs and their families, that being open about
      one's HIV status to one's community is positively associated with receiving
      modern treatment for HIV-related ailments, that being female is negatively
      associated with receiving modern treatment and that living upcountry (as opposed
      to living in Bangkok) is associated with using herbal remedies. Policy
      implications of the findings are discussed.

PMID- 16971271
TI  - Living environment and schooling of children with HIV-infected parents in
      southwest China.
AB  - A cross-sectional household survey was conducted in Longchuan County, China, to
      study the lives of children with HIV-infected parents. Registered HIV-infected
      drug users and their households were approached and information about the living
      environment of children < or =15 years of age was collected. Of the 266
      households interviewed, there were 213 children < or =15 years old. Forty percent
      of the children had lost at least one parent. Most of the children resided in a
      household with low economic status and a high dependency ratio. One-half of the
      children experienced discordant family relations, family anxiety and shame.
      Compared to orphans, non-orphans and their families were less likely to receive
      social support from the community. Orphans and older children were less likely to
      attend school and more likely to be truant if enrolled in school. Findings in the
      current study suggest that many children whose parents are infected with HIV or
      have died from HIV are living in stressful environments with minimal support from
      the community. Efforts should be taken to provide support and supervision to
      these children.

PMID- 16971272
TI  - HIV/AIDS, income loss and economic survival in Botswana.
AB  - In countries facing severe HIV/AIDS epidemics, the overwhelming majority of those
      who are infected and affected by HIV are already living in poverty. Further
      income loss can threaten the ability to meet basic needs such as food, education
      and access to healthcare. Due to this, understanding the impact of HIV infection
      and caregiving on household income is essential to improving the health and
      welfare of HIV-affected individuals and families. This qualitative study examines
      how HIV infection and HIV caregiving affect household income in a population
      located within Botswana, a country with high HIV prevalence. We find that
      extended unpaid leave from work or job loss are common consequences and are
      associated with failure to meet basic needs in the short and long-term. We make
      recommendations for policy and programme support, including workplace adaptations
      and public sector support for meeting health and basic needs of HIV-affected
      families.

PMID- 16971274
TI  - Publishing HIV/AIDS behavioural science reports: An author's guide.
AB  - The purpose of this paper is to report on characteristics of journals that
      publish manuscripts in the HIV/AIDS behavioural science realm, with the goal of
      providing assistance to authors seeking to disseminate their work in the most
      appropriate outlet. Fifty journals who publish behavioural research on HIV/AIDS
      in English were identified through library and electronic searches. Although ten
      of the journals focused specifically on HIV/AIDS, the majority of journals are in
      related fields, including health psychology/behavioural medicine, sexual
      behaviour, substance abuse, public health/prevention or general medicine.
      Acceptance rates ranged from 8- 89% with a mean acceptance rate of 39%. Reported
      review times ranged from 1-12 months with three months the mode, while
      publication lag following acceptance averages six months. Acceptance rates were
      related to impact factors, with more selective journals evidencing higher impact
      factors. The variety of publication outlets available to authors of HIV/AIDS
      behavioral science studies creates ample opportunity for dissemination, as well
      as challenge for readers in discerning the quality of published work.

PMID- 16971273
TI  - Balancing disfigurement and fear of disease progression: Patient perceptions of
      HIV body fat redistribution.
AB  - This study was conducted to identify and describe the perceived morphologic
      changes of body fat redistribution and related distress among persons taking
      combination antiretroviral therapy. Six focus group interviews were conducted in
      four different US cities with men and women (n = 58) who reported antiretroviral
      related symptoms of body fat loss and/or gain. Interview data were audiotaped,
      transcribed verbatim and systematically analysed using inductive techniques.
      Physical discomfort and impairment and psychological and social distress were
      reported across sex, sexual orientation and geographic subgroups. While
      participants acknowledged that antiretroviral drugs were keeping them alive,
      there was tension between the desire for life-sustaining treatment and optimal
      quality of life. Some participants engaged in harmful heath behaviours in an
      attempt to control bodily changes (e.g. non-adherence to antiretroviral regimen).
      Participants feared that fat loss represented disease progression and worried
      that visible changes would lead to unintentional disclosure of their HIV status.
      Although a potential source of support, healthcare providers were commonly
      perceived as ignoring and, in so doing, discrediting patient distress.
      Participants recognised the limitations of current lipodystrophy treatment
      options, yet a cure for the syndrome seemed less important to them in the short
      term than simply being listened to and the powerful, but oblique sources of
      distress addressed.

PMID- 16971275
TI  - Sexual violence among two populations of men at high risk of HIV infection.
AB  - This study sought to compare the prevalence of, and relationship between, age at
      first experience of sexual violence and HIV and other health risk behaviors in
      two populations of men at high risk of HIV infection. Data were drawn from two
      cohorts: Vanguard, a prospective study of young men who have sex with men (MSM),
      and VIDUS, the Vancouver Injection Drug Users Study. Controlling for fixed
      sociodemographics, multivariate logistic regression was used to assess the
      relationship between age at first sexual violence (vs. never experiencing it) and
      several health risk behaviors. There were 140/498 (28%) MSM from Vanguard and
      173/932 (19%) injection drug users (IDU) from VIDUS who reported having
      experienced sexual violence. Among VIDUS men, 130/852 (15%) IDU-only and 43/80
      (54%) who were both IDU and MSM reported a history of sexual violence. The
      prevalence of child sexual abuse was 13% in Vanguard MSM, and 11% among VIDUS IDU
      only, but 26% among VIDUS MSM/IDU. The median age of onset was significantly
      lower among VIDUS IDU-only compared to the two other groups. Experiencing sexual
      violence first in childhood was strongly related to ever being in the sex trade
      in both IDU and MSM. MSM in Vanguard who experienced sexual violence in childhood
      were more likely to have attempted suicide, and have a diagnosed mood disorder.
      Non-MSM IDU in VIDUS who experienced sexual violence in childhood were more
      likely to have a diagnosed mental illness, to binge on alcohol, and to have ever
      accidentally overdosed. In conclusion, men who have ever had sex with men appear
      to have a higher lifetime prevalence of sexual violence, compared to non-MSM
      injection drug users. Sexual violence is differentially associated with different
      health risk behaviors, depending on the age at first occurrence and the primary
      HIV risk factor (i.e. MSM vs. IDU).

PMID- 16971276
TI  - Differences in access to care among injection drug users infected either with HIV
      and hepatitis C or hepatitis C alone.
AB  - Access to HCV (Hepatitis C virus) care for HIV/HCV-co-infected patients is an
      urgent public health concern. The objective of the present study was to describe
      the self-reported health status of HIV/HCV-co-infected and HCV-mono-infected
      injection drug users and to describe their access to HCV-related care. Beginning
      in May 1996, persons who had injected illicit drugs in the previous month were
      recruited into the Vancouver Injection Drug User Study (VIDUS). At baseline and
      then semi-annually, participants complete an interviewer-administered
      questionnaire. Blood is drawn at each semi-annual interview and tested for HIV
      and Hepatitis C infection. Data for this descriptive, cross-sectional study were
      drawn from the most recent of either the July 2003 or December 2003 nurse
      administered questionnaire. Statistics used were the chi-square, Wilcoxon Rank
      Sum and Student's t-test. Logistic regression was used to examine factors
      independently associated with accessing HCV care. There were 707 individuals
      eligible for this analysis, including 240 HIV/HCV-co-infected and 467 HCV-mono
      infected persons. Co-infected individuals were more likely to be female, younger,
      of Aboriginal ethnicity and less likely to use heroin daily. The HCV-mono
      infected group tended to report higher rates of HCV-related symptoms, including
      fatigue, liver pain, nausea, night-sweats and stomach pain. However, it was the
      HIV/HCV-co-infected group who were more likely to report that they believed their
      hepatitis C was affecting them. The HIV/HCV-co-infected group were also more
      likely to report having received any hepatitis-related follow-up care, including
      blood work, liver biopsies and referrals to specialists. In logistic regression
      analysis, factors independently associated with ever receiving any hepatitis C
      related follow-up were HIV/HCV-co-infection (AOR 3.1; 95% CI: 2-4.7), being older
      (AOR 1.04; 95% CI: 1.02-1.06 per year older), using heroin daily (AOR 0.54; 95%
      CI: 0.36-0.82) and believing that hepatitis C was affecting one's health (AOR
      1.4; 95% CI: 1.0-2.1). In conclusion, our data indicate more HCV healthcare
      utilization among those HIV/HCV-co-infected.

PMID- 16971277
TI  - Care burden and self-reported health status of informal women caregivers of
      HIV/AIDS patients in Kinshasa, Democratic Republic of Congo.
AB  - We conducted a cross-sectional study on women who were caregivers of HIV/AIDS
      affected spouses in Bumbu in Kinshasa, Democratic Republic of Congo. The sample
      consisted of 80 women randomly selected from a client visitation list of the home
      based care program for AIDS patients. A semi-structured questionnaire was
      applied. A self-reported health status was calculated with five items from the
      questionnaire. The self-reported health status score of participants indicated
      poor health. The study highlights the great burden on caregivers in sub-Saharan
      Africa.

PMID- 16971278
TI  - A conceptual model of women's condom use intentions: Integrating intrapersonal
      and relationship factors.
AB  - We developed and tested a multifaceted model of condom use intentions with cross
      sectional data from 435 heterosexual women at risk for HIV/STIs. In addition to
      traditional intrapersonal variables drawn from established models of HIV
      prevention (e.g. attitudes, norms, self-efficacy), the present study examined the
      role of relationship factors and dynamics (i.e. relationship commitment,
      duration, condom use and pregnancy prevention decision-making) in shaping condom
      use intentions. In some cases, relationship variables were directly associated
      with condom use intentions. In other cases their effects on condom use intentions
      were mediated by intrapersonal constructs. The final model accounted for 66% of
      the variance in condom use intentions and confirmed the importance of integrating
      intrapersonal variables and relationship characteristics and dynamics in
      understanding women's intentions to use condoms. These results offer important
      insights for the design of interventions directed at promoting condom use among
      young women at risk for HIV/STIs and underscore the need to design prevention
      programs that address relationship characteristics and dynamics.

PMID- 16971279
TI  - Vulnerability and risk factors for sexually transmitted infections and HIV among
      adolescents in Kampala, Uganda.
AB  - Three hundred and six sexually experienced adolescents participated in a study on
      sexually transmitted infection (STI) prevalence and associated risk factors. The
      prevalence of Neisseria gonorrhoea (NG), Chlamydia trachomatis (CT), Trichomonas
      vaginalis (TV) and syphilis was 4.5%, 9%, 8% and 4% for females and 4.7%, 5.7%,
      0% and 2.8% for males. HIV-seropositivity was found in 15.2% of females and 5.8%
      of males. Structured face-to-face interviews were used to obtain information
      about social background, sexual experience and genital symptoms. Four focus-group
      discussions were used in order to validate the interview data. Females were more
      likely to be infected by the four treatable STIs and HIV, despite risky behavior
      being more common among males. Unemployment, little formal education, the
      presence of bacterial STIs and post-coital bleeding or a bad smell from the
      vagina was highly associated with the risk for HIV in females. The higher
      prevalence of STIs, including HIV, among adolescent girls cannot be explained by
      sexual behavior only, as boys reported more risk behavior and were still less
      affected by STIs. Biological and social factors are definitely of importance.

PMID- 16971280
TI  - HIV-related knowledge, stigma, and willingness to disclose: A mediation analysis.
AB  - Increasing HIV knowledge is a focus of many HIV education and prevention efforts.
      While the bivariate relationship of HIV serostatus disclosure with HIV-related
      knowledge and stigma has been reported in the literature, little is known about
      the mediation effect of stigma on the relationship of HIV knowledge with HIV
      serostatus disclosure. Data from 4,208 rural-to-urban migrants in China were
      analyzed to explore this issue. Overall, 70% of respondents reported willingness
      to disclose their HIV status if they were HIV-positive. Willingness to disclose
      was negatively associated with misconceptions about HIV transmission and stigma.
      Stigma mediated the relationship between misconceptions and willingness to
      disclose among women but not men. The mediation effect of stigma suggests that
      stigmatization reduction would be an important component of HIV prevention
      approaches. Gender inequality needs to be addressed in stigmatization reduction
      efforts.

PMID- 16971281
TI  - Effect of antiretroviral treatment and counselling on disclosure of HIV
      serostatus in Johannesburg, South Africa.
AB  - This prospective non-randomized study of clinic attendees, compares self-reported
      HIV disclosure patterns in relation to access to antiretroviral access and
      counselling. It was carried out in public sector hospital HIV clinics in
      Johannesburg, South Africa, and 144 HIV-positive men and women attending the HIV
      clinics participated in the study.The results showed that there was no
      correlation between being on antiretroviral therapy and disclosure of HIV status.
      There was also no correlation between disclosure of HIV status and with different
      levels of counselling and access to support groups. Disclosure levels were high
      (92% told at least one person), however, there was a high level of delayed (15%
      greater than a year) or non-disclosure (21%) to partners. Family members and
      partners provided most moral support after disclosure. Having access to
      antiretroviral therapy and support groups and available counselling did not seem
      to affect disclosure patterns. It is possible that a patients beliefs about their
      treatment plays a more important role for disclosure than the actual treatment
      itself. Other factors are also likely important for disclosure, such as the
      patient's social network especially with their families, and knowledge of the
      disease.

PMID- 16971282
TI  - Practicing HIV/AIDS community-based research.
AB  - Although community-based research (CBR) is gaining popularity, especially within
      the field of HIV/AIDS research, there is a paucity of practical models or
      frameworks designed to guide researchers and community members. Within the
      present paper the author presents a ten-stage model of conducting CBR that
      emerged from two HIV/AIDS CBR studies that were conducted in Alberta, Canada. The
      main strengths and challenges to conducting HIV/AIDS CBR are also explored.
      Living a life with HIV has changed dramatically over the past few decades. There
      have been notable improvements in medical technology and treatment, resulting in
      increased quality and duration of life (Volberding, 1998; Wong-Staal, 1997) as
      well as improvements in psychosocial interventions leading to improved mental
      health services (Grinstead & Van Der Straten, 2000; Hoffman, 1996; Sarwer &
      Crawford, 1994; Schaffner, 1994). Perhaps most significant has been the
      astonishing community rallying and social support networks that have occurred
      among individuals living with HIV and AIDS (Roy & Cain, 2001). People living with
      HIV and AIDS have demonstrated their resilience and positive outlooks through
      developing a multitude of community connections and projects. These
      organizational groups have engaged in HIV peer counselling at community-based
      organizations, fund raising programs, board involvement in community agency
      organizations and HIV/AIDS national committees, as well as volunteer work in many
      settings. There has also been a recent focus on CBR, which includes having
      individuals living with HIV and AIDS, people vulnerable to HIV infection or other
      stakeholders in HIV/AIDS issues become partners in research projects with
      academic or trained researchers (Health Canada, 2002).

PMID- 16971283
TI  - The role of collectives in STI and HIV/AIDS prevention among female sex workers
      in Karnataka, India.
AB  - This paper evaluates the role of female sex worker (FSW) collectives in the state
      of Karnataka, India, regarding their facilitating effect in increasing knowledge
      and promoting change towards safer sexual behaviour. In 2002 a state-wide survey
      of FSWs was administered to a stratified sample of 1,512 women. Following the
      survey, a collectivization index was developed to measure the degree of
      involvement of FSWs in collective-related activities. The results indicate that a
      higher degree of collectivization was associated with increased knowledge and
      higher reported condom use. Reported condom use was higher with commercial
      clients than with regular partners or husbands among all women and a gradient was
      observed in most outcome variables between women with low, medium and high
      collectivization index scores. Collectivization seems to have a positive impact
      in increasing knowledge and in empowering FSWs in Karnataka to adopt safer sex
      practices, particularly with commercial clients. While these results are
      encouraging, they may be confounded by social desirability, selection and other
      biases. More longitudinal and qualitative studies are required to better
      understand the nature of sex worker collectives and the benefits that they can
      provide.

PMID- 16971284
TI  - Condoms + pleasure = safer sex? A missing addend in the safer sex message.
AB  - Since the emergence of HIV, sexual risk-reduction intervention and prevention
      programmes have promoted the 'condoms equal safer sex' message with a particular
      focus on the preventative aspects of condoms (i.e. disease or pregnancy
      prevention). Yet despite the pervasiveness of this message, research has found
      that most people fail to use condoms consistently. Using the thought-listing
      technique, we asked men who have sex with men (MSM) and heterosexuals to list
      thoughts that immediately came to mind when thinking about condoms. Results show
      that MSM have more sexual/sensory associations to condoms than heterosexuals,
      suggesting that interventions highlighting the sexual/sensory aspects of condoms
      might be an important component to increase condom use among MSM while a combined
      approach (i.e. messages that integrate preventative, interpersonal, and
      sexual/sensory components) might be more appealing to heterosexuals.

PMID- 16971285
TI  - Immunisation coverage among children born to HIV-infected women in Rakai
      district, Uganda: Effect of voluntary testing and counselling (VCT).
AB  - To evaluate the impact of maternal HIV-infection on routine childhood
      Immunisation coverage, we compared the Immunisation status of children born to
      HIV-infected and HIV-uninfected women in rural Uganda. The study population was
      214 HIV(+) and 578 HIV(-) women with children aged 6 to 35 months previously
      enrolled in a community study to evaluate maternal and child health in Rakai
      District, Uganda. Sampling of subjects for interview was stratified by the use of
      voluntary counselling and testing (VCT) service so that the final sample was four
      groups: HIV + /VCT+ (n = 98); HIV + /VCT- (n = 116); HIV - /VCT+ (n= 348); HIV -
      /VCT- (n = 230). The main outcome measure was the percent of complete routine
      childhood Immunisations recommended by the WHO as assessed from Immunisation
      cards or maternal recall during household interviews. We found that Immunisation
      coverage in the overall sample was 26.1%. For all vaccines, children born to HIV
      infected mothers had lower Immunisation coverage than children born to HIV
      negative mothers (21.3 vs. 27.7%). There was a statistically significant
      interaction between maternal HIV-infection and maternal knowledge of HIV
      infection (p = 0.034). The children of mothers who were HIV-infected and knew
      their serostatus (HIV + /VCT + ) had a more than two-fold odds of
      underImmunisation (OR = 2.21, 95% CI: 1.14, 4.29) compared to children of mothers
      who were HIV - /VCT-. We conclude that maternal HIV-infection was associated with
      childhood underImmunisation and this was mediated by a mother's knowledge of her
      HIV status. HIV VCT programmes should encourage HIV-infected mothers to complete
      childhood Immunisation. Improving access to Immunisation services could benefit
      vulnerable populations such as children born to HIV-infected mothers.

PMID- 16971286
TI  - Limitations in knowledge of HIV transmission among HIV-positive patients
      accessing case management services in a resource-poor setting.
AB  - HIV has increasingly become an infection of poverty. Adequate HIV transmission
      knowledge among HIV-positive patients is necessary to reduce the risk of
      secondary infection and protect those who are uninfected from transmission. This
      study was conducted among individuals enrolled in a program that serves
      impoverished HIV patients in the Boston area. Although the mean HIV transmission
      knowledge score was 80% for this group, a significant proportion of patients
      demonstrated limitations in knowledge of HIV transmission. Highly vulnerable
      patients, such as those who reported not accessing HIV medications, a history of
      sexual abuse, or problems getting clothing, had lower levels of HIV knowledge.
      This paper hopes to alert providers that their most vulnerable patients may be at
      an increased risk of re-infection or transmission due to limited HIV knowledge.
      Programs that serve HIV-positive patients coping with poverty and other serious
      problems need to ensure adequate knowledge of HIV transmission to reduce the
      overall burden of HIV in resource-poor settings.

PMID- 16971287
TI  - Community attitudes towards sexual activity and childbearing by HIV-positive
      people in South Africa.
AB  - While the ability to lead a healthy sexual life and to choose whether and when to
      have children are well-established features of reproductive health and human
      rights, issues surrounding sexual activity and childbearing among HIV-infected
      women and men have received little attention in sub-Saharan Africa. We conducted
      a semi-structured, cross-sectional survey at 26 primary health care clinics in
      South Africa to investigate community attitudes towards sexual activity and
      reproduction by HIV-infected individuals. Of the 843 women interviewed, slightly
      less than half (43%, n = 361) thought that people living with HIV/AIDS should
      remain sexually active if they choose, while 13% (n = 113) said they thought that
      people living with HIV/AIDS should have children if they wished to do so. In
      multivariate analysis, negative attitudes towards both sexuality and childbearing
      were persistently associated with not knowing someone infected with HIV (p =
      0.001 and 0.043, respectively). These findings suggest that the sexual and
      reproductive health rights of HIV-infected women and men may be an important
      target as part of efforts to reduce HIV/AIDS-related stigma. Health policies and
      services are required to reinforce the reproductive rights of HIV-infected
      individuals in South Africa and other countries in sub-Saharan Africa where HIV
      is most prevalent.

PMID- 16971288
TI  - Unprotected intercourse for extra money among commercial sex workers in Kinshasa,
      Democratic Republic of Congo.
AB  - This study assessed the extent and correlates of the practice of engaging in
      unprotected intercourse for extra money among commercial sex workers (CSWs) in
      Kinshasa, Democratic Republic of the Congo. We conducted a cross-sectional survey
      using a structured, interviewer-administered questionnaire among a convenience
      sample of 136 CSWs. More than one-quarter of CSWs (26.5%) engaged in unprotected
      intercourse for extra money. These CSWs charged about 3.5 times more for
      unprotected intercourse than for protected intercourse. Multivariate logistic
      regression showed that CSWs who engaged in unprotected intercourse for extra
      money were significantly more likely to live or work in non-downtown (lower
      socioeconomic) areas of Kinshasa (odds ratio [OR] = 3.07), to have at least one
      child less than six years of age (OR = 2.95), and to know other CSWs who engaged
      in the same practice (OR = 9.38). We hypothesize that desperate socioeconomic
      conditions combined with peer/social norms drive the practice of engaging in
      unprotected intercourse for extra money. Additional circumstances under which
      Kinshasa CSWs engaged in unprotected intercourse included intercourse with
      clients who tore their condoms to increase sexual pleasure (58.8% of CSWs),
      episodes of condom failure (56.8% of CSWs), and unprotected intercourse with
      regular noncommercial partners (only 5.3% of CSWs with noncommercial partners
      always used condoms with these partners).

PMID- 16971289
TI  - Gender differences in attitudes toward AIDS clinical trials among urban HIV
      infected individuals from racial and ethnic minority backgrounds.
AB  - Racial/ethnic minorities and women are under-represented in AIDS clinical trials
      (ACTs). We examined gender differences in willingness to participate in ACTs
      among urban HIV-infected individuals (N = 286). Sixty percent of participants
      were male, and most were from racial/ethnic minority backgrounds (55% African
      American, 34% Latino/Hispanic, 11% White/other). Knowledge of ACTs was poor.
      Males and females did not differ substantially in their distrust of AIDS
      scientists, or in barriers to ACTs. Almost all (87%) were somewhat or very
      willing to join ACTs. Females were less willing than males to join, including
      trials testing new medications or new medication combinations. Males and females
      differed in correlates of willingness to participate in ACTs. Despite long
      standing barriers to medical research among minorities and women, willingness to
      participate was substantial, particularly for men, although the factors that
      might motivate them to join differed by gender. Women appeared more averse to
      trials involving new anti-retroviral regimens than men. Gender-specific outreach,
      behavioural intervention, and social marketing efforts are needed.

PMID- 16971290
TI  - Oral contraception and unprotected sex with occasional partners of women HIV
      infected through injection drug use.
AB  - Among HIV-infected women, unprotected sex with the main sexual partner is common
      practice. Conversely, studies about condom use with sexual partners of unknown
      HIV sero-status are sparsely reported. We aimed to assess the impact of oral
      contraception on unsafe sexual behaviours with occasional partners in women HIV
      infected through injection drug use. The analysis focused on 90 women, enrolled
      in the French cohort MANIF 2000 and reported having engaged in sexual
      relationships with occasional partners during a 48-month period. Visits where
      women reported unprotected sex with occasional partners in the prior 6 months
      were compared to visits where they reported protected sex using a logistic model
      based on Generalised Estimating Equations. Unprotected sex with occasional
      partners was independently associated with oral contraception (OR[95%CI] =
      3.2[1.4-7.2]), reporting only one occasional partner (OR[95%CI] = 3.1[1.6-6.2])
      and antiretroviral treatment receipt. No significant association was found
      between unprotected sex and CD4 level or plasma viral load. With the growing
      population of people living with HIV as a chronic infection, the development and
      evaluation of HIV-prevention interventions tailored toward women remain a public
      health priority. Risk reduction counselling and interventions are needed to
      promote either the use of dual contraception or, alternatively, that of female
      condom.

PMID- 16971291
TI  - Unprotected intercourse among people living with HIV/AIDS: The importance of
      partnership characteristics.
AB  - The purpose of this study was to determine the relative importance and
      interactive effects of partnership characteristics in unprotected intercourse
      among people living with HIV/AIDS (PLWHA). An interview study was conducted among
      a convenience sample of PLWHA in care. Of all the demographic, health status,
      risk history and behaviors and partnership covariates explored, only the
      partnership covariates were significantly associated with unprotected
      intercourse. Significant covariates included having a steady partner (OR and
      95%CI = 4.2; 1.3, 13.5), HIV-positive (OR and 95%CI = 2.7; 1.0, 6.9 versus HIV
      negative partner) or unknown serostatus partner (OR and 95%CI = 4.6; 1.1, 18.3
      versus HIV-negative partner) and men who have sex with men (MSM) partnerships (OR
      and 95%CI = 3.0; 1.2, 7.3). Partnership covariates explained 23% of the variance
      in unprotected intercourse; other groups of covariates did not significantly
      improve model fit. Significant interaction terms between reported partner HIV
      status, partnership type and sexual orientation revealed the greatest likelihood
      of unprotected intercourse in two groups of individuals: those in steady
      relationships with HIV-positive partners and MSM in relationships with partners
      of unknown serostatus. Prevention interventions for PLWHA should focus on
      partnership characteristics.

PMID- 16971292
TI  - Attitudes toward directly administered antiretroviral therapy (DAART) among HIV
      positive inpatients in an inner city public hospital.
AB  - Directly administered antiretroviral therapy (DAART) is one approach to improve
      adherence among HIV-positive individuals. DAART has been assessed for confined
      participants such as prisoners and for patients enrolled in methadone clinics but
      community-based voluntary DAART programs are not well studied. We examined the
      attitudes toward DAART among 47 HIV-positive inpatients in an inner city public
      hospital, a population difficult to engage in conventional self-administered
      highly active antiretroviral therapy (HAART). This study found that 83% of
      participants prefer self-administered therapy (SAT) and only 17% elect for DAART.
      A significant proportion of participants think the approach is intrusive or
      impractical and few are willing to meet with providers daily. A proportion of our
      patients, however, struggle with medication non-adherence and fragmented medical
      care, evident in the high rates of missed clinic appointments, frequent emergency
      department visits and repeated hospitalizations. These data can inform the
      development of DAART programs and suggest that considerable effort is needed to
      'sell' the idea of DAART to this patient population. It is likely that such
      patients will greatly benefit from a clinic that can provide intensive
      counseling, frequent follow-up, home visits and DAART. Patient education
      regarding the merits of such an approach will be key to success.

PMID- 16971293
TI  - Factors associated with postpartum physical and mental morbidity among women with
      known HIV status in Lusaka, Zambia.
AB  - The objective of our study was to investigate factors associated with postpartum
      physical and mental morbidity among women in Lusaka, Zambia with particular
      reference to known HIV status. Our study was part of the Breastfeeding and
      Postpartum Health (BFPH) longitudinal cohort study conducted between June 2001
      and July 2003. Women were recruited at 34 weeks gestation and followed up to 16
      weeks postpartum. Data on maternal health were collected at 3, 7, 10, and 14 days
      and at 3, 4, 5, 6, 9, 12, and 16 weeks postpartum. Maternal mental health data
      were collected from April 2002 onwards at recruitment and at seven days and six
      weeks postpartum. Data on physical morbidity were collected for 429 women (218
      HIV-negative, 211 HIV-positive) and data on mental morbidity were collected for
      272 women (134 HIV-negative, 138 HIV-positive). Multivariate logistic regression
      was used to examine factors associated with postpartum physical or mental
      morbidity. Postpartum physical morbidity was associated with HIV status, parity >
      or =5 and age < 20 years. Neither antenatal nor postpartum mental morbidity, as
      indicated by a self-reporting questionnaire 20-item (SRQ-20) score > or =7, were
      associated with HIV status or with postpartum physical morbidity in this
      population. Larger comparative studies are required to corroborate or contest
      these findings.

PMID- 16971294
TI  - Factors affecting attrition in a longitudinal study of patients with AIDS.
AB  - Anecdotal data have suggested that retention of HIV-infected patients with immune
      recovery in longitudinal studies may be difficult as they resume normal
      activities. This study evaluated risk factors for attrition among patients with
      AIDS in a cohort study in the era of highly active antiretroviral therapy.
      Patients with AIDS enrolled in the Longitudinal Study of Ocular Complications of
      AIDS were evaluated every three months with demographic, clinical and laboratory
      data collected. Lost to follow-up was defined as any patient who missed all study
      visits and could not be contacted for 12 consecutive months, who had not died and
      who did not re-enter the study at a later date. Of the 1,052 patients studied, 77
      (7.3%) were lost to follow-up (rate = 0.03/person year). In the multivariate
      analysis, factors associated with attrition were CD4+ T-cell count category
      (hazard ratio (HR) = 2.03; 95%CI: 1.01, 4.24; P = 0.05 for CD4+ count < or = 50
      cells/microL and HR = 1.96; 95%CI: 1.12, 3.40; P = 0.02 for CD4+ count 51-200
      cells/microL) and detectable HIV viral load (HR = 1.29; 95%CI: 1.07, 1.53; P <
      0.001 for HIV viral load >400 copies/mL). These data suggest that patients with
      compromised immunologic status are at an increased risk for being lost to follow
      up.

PMID- 16971295
TI  - A randomized controlled psycho-education intervention trial: Improving
      psychological readiness for successful HIV medication adherence and reducing
      depression before initiating HAART.
AB  - The purpose of this study was to evaluate a novel psycho-educational intervention
      intended to increase patients' medication preparedness and treatment adherence
      skills before initiating highly active antiretroviral therapy (HAART). Sixty
      three HIV-positive patients not currently on antiretroviral therapy participated
      in a randomized controlled trial of a standardized, four-session psycho
      educational intervention (Supportive Therapy for Adherence to Antiretroviral
      Treatment; STAART). Session topics included learning techniques to increase
      medication adherence and learning effective strategies to cope with stress and
      depression. Patients completed psychological questionnaires assessing
      psychological readiness to initiate HAART and depressed mood. They completed both
      measures at study baseline and at four-weeks post-baseline. After controlling for
      baseline medication readiness scores, intervention patients (n = 30) reported
      significantly higher mean medication readiness following the STAART intervention
      (four-weeks post-baseline) (27.3+/-6.9) compared to controls (n = 33; 24.6+/-9.9;
      p < 0.05). Among depressed patients (n = 27), those receiving the intervention (n
      = 15) reported significantly lower mean depression scores at four-weeks post
      baseline (22.5+/-12.9) compared to controls (n = 12; 27+/-9.9; p < 0.05). The
      STAART intervention enhanced HIV treatment readiness by better preparing patients
      prior to initiating HAART. It was also beneficial for reducing depressive
      symptoms in depressed, HIV-positive patients.

PMID- 16971296
TI  - Transtheoretical Model and substance use in HIV-positive youth.
AB  - The purpose of the study was to test constructs of the Transtheoretical Model
      (TTM) for predicting alcohol and other drug use in HIV-positive youth (ages 16
      25). Questionnaires and interviews about alcohol and other drug use, stage of
      change, self-efficacy, emotional distress and social support were obtained from
      64 HIV-positive youth. Structural equation modeling with standard errors
      determined by methods appropriate to small samples, demonstrated that self
      efficacy mediated the relationship between stage of change and alcohol use and
      between social support and alcohol use. The same pattern of results emerged for
      marijuana use. The models predicted 47% of the variance in alcohol use and 69% of
      the variance in marijuana use. Results supported the TTM and highlight the
      potential of interventions that seek to boost self-efficacy and social support
      specific to reducing substance use.

PMID- 16971297
TI  - Stigma and HIV infection in Russia.
AB  - Few studies have examined the personal and social consequences of stigma
      associated with HIV infection in Russia, a country with one of the most rapidly
      advancing HIV epidemics globally. By May 2005, Samara Oblast, Russia had 24,022
      notified seropositive individuals. Focus-group discussions with randomly sampled
      seropositive and seronegative individuals, matched by age, gender and education
      were selected from the general population and used to provide an informal forum
      for discussion of attitudes to HIV and potentially stigmatizing behavior. The
      results demonstrated that the perception that HIV was associated with immoral
      behaviour underpinned stigma. Discriminating attitudes are strongly associated
      with misperceptions regarding transmission and frequent over-estimation of risks
      from casual contact. The general population was unforgiving to those who had
      become infected sexually or through drug use. Infection through a medical
      procedure or from an assault was perceived as a likely route of infection.
      Knowledge of population attitudes and perceptions, as well as those who are HIV
      positive, is critical for successful interventions and to encourage people to
      come forward for HIV testing. This research offers insights into the distance
      that needs to be traveled if stigma is to be addressed in wider efforts to
      control HIV in Russia.

PMID- 16971300
TI  - Simultaneous detection of creatine and creatinine using a sequential injection
      analysis/biosensor system.
AB  - Carbon paste based biosensors for the determination of creatine and creatinine
      have been integrated into a sequential injection system. Applying the multi
      enzyme sequence of creatininase (CA), and/or creatinase (CI) and sarcosine
      oxidase (SO), hydrogen peroxide has been detected amperometrically. The linear
      concentration ranges are of pmol/L to nmol/L magnitude, with very low limits of
      detection. The proposed SIA system can be utilized reliably for the on-line
      simultaneous detection of creatine and creatinine in pharmaceutical products, as
      well as in serum samples, with a rate of 34 samples per hour and RSD values
      better than 0.16% (n=10).

PMID- 16971298
TI  - The CASE adherence index: A novel method for measuring adherence to
      antiretroviral therapy.
AB  - The Center for Adherence Support Evaluation (CASE) Adherence Index, a simple
      composite measure of self-reported antiretroviral therapy (ART) adherence, was
      compared to a standard three-day self-reported adherence measure among
      participants in a longitudinal, prospective cross-site evaluation of 12 adherence
      programs throughout the United States. The CASE Adherence Index, consisting of
      three unique adherence questions developed for the cross-site study, along with a
      three-day adherence self-report were administered by interviews every three
      months over a one-year period. Data from the three cross-site adherence questions
      (individually and in combination) were compared to three -day self-report data
      and HIV RNA and CD4 outcomes in cross-sectional analyses. The CASE Adherence
      Index correlated strongly with the three-day self-reported adherence data (p <
      0.001) and was more strongly associated with HIV outcomes, including a 1-log
      decline in HIV RNA level (maximum OR = 2.34; p < 0.05), HIV RNA < 400 copies/ml
      (maximum OR = 2.33; p < 0.05) and performed as well as the three-day self-report
      when predicting CD4 count status. Participants with a CASE Index score >10
      achieved a 98 cell mean increase in CD4 count over 12 months, compared to a 41
      cell increase for those with scores < or =10 (p < 0.05). The CASE Adherence Index
      is an easy to administer instrument that provides an alternative method for
      assessing ART adherence in clinical settings.

PMID- 16971301
TI  - Kinetics of the oxidoreductase involved in the conversion of O
      methylsterigmatocystin to aflatoxin B1.
AB  - Among the enzymatic steps in the aflatoxin biosynthetic pathway, the conversion
      of O-methylsterigmatocystin (OMST) to the potent environmental carcinogen
      aflatoxin B1 (AFB1), has been proposed to be catalysed by an oxidoreductase (OR)
      that requires a cytochrome P-450 type of oxidoreductase activity. This enzyme
      displays relative specificity towards OMST homologues in fungal whole cells.
      These studies were extended to the action of a cell-free enzyme system (CFES), on
      five OMST homologues, with a view to establish the kinetics. In the current study
      a CFES, containing an oxidoreductase, was derived from a blocked mutant of
      Aspergillus parasiticus (Wh1-11-105). The key experimental steps involved rapid
      concentration and efficient dialysis by membrane filtration to remove small
      biomolecules (MW<10,000), co-factors, primary and secondary metabolites. The
      kinetic parameters of the enzyme-substrate reactions indicated that the reaction
      follows a Michealis-Menten kinetics and OR activity decreased in the order: O
      butylsterigmatocystin>O-propylsterigmatocystin>O-ethylsterigmatocystin>O
      methylsterigmatocystin>O-acetylsterigmatocystin>O-benzoylsterigmatocystin. The 7
      O-alkyl homologues were the best substrate for the CFES, thereby substantially
      supporting that the 7-O-methyl group of OMST is preferred for OR catalytic
      activity in the absence of any other alkylating groups in vitro. The Km was
      calculated as 5.65 microM for this CFES and varied marginally among the OMST
      homologues studied.

PMID- 16971302
TI  - NAD+ mediated differential thermotolerance between chloroplastic and cytosolic L
      myo-inositol-1-phosphate synthase from Diplopterygium glaucum (Thunb.) Nakai.
AB  - Relative thermotolerance of the enzyme, L-myo-inositol-1-phosphate synthase
      (MIPS; EC: 5.5.1.4), from the chloroplastic and cytosolic sources of
      Diplopterygium glaucum was studied. The purification involved streptomycin
      sulphate precipitation, ammonium sulphate fractionation, ion-exchange
      chromatography, and molecular sieve chromatography. After the final
      chromatography, 16.62% of chloroplastic and 13.47% of cytosolic MIPS could be
      recovered. Between 15 degrees C and 55 degrees C, the two forms of MIPS exhibited
      differential thermal stability, which is related to the presence of the MIPS co
      factor, NAD+. Added NAD+ increased the lower thermotolerance of the chloroplastic
      MIPS and the removal of 'built-in' NAD+ decreased the higher thermal stability of
      the cytosolic MIPS.

PMID- 16971303
TI  - Bioconversion of methanol to formaldehyde. II. By purified methanol oxidase from
      modified yeast, Hansenula polymorpha.
AB  - Modified methylotrophic yeast Hansenula polymorpha (HP A16) that was obtained by
      repressing leucine oxotrophic yeast; a wild type of Hansenula polymorpha CB4732
      was used in this study. The yeast is grown with methanol, which is used as a sole
      carbon source, using various methanol concentrations and temperatures, and
      methanol oxidase (MOX) which is a key enzyme of methanol metabolism; production
      is maximized. Whole yeast cells were cultivated under optimized inoculation
      conditions; they were separated into two portions. One portion of these cells was
      directly used in bioconversion of methanol to formaldehyde. The second portion of
      the free cells was broken into pieces and a crude enzyme extract was obtained.
      The MOX enzyme in this extract was purified via salt precipitation, dialysis, and
      chromatographic methods. The purified MOX enzyme of yeast (HP A16) oxidized the
      methanol to formaldehyde. Optimization of bioconversion conditions was studied to
      reach maximum activity of enzyme. The optimum temperature and pH were found to be
      35 degrees C and pH 8.0 in boric acid/NaOH buffer, and it was stable over the pH
      range of 6-9, at the 20 degrees C 15 min. A suitable reaction period was found as
      50 min. The enzyme indicated low carbon primary alcohols (C2 to C4), as well as
      methanol. Initially, MOX activity increased with the increase of methanol
      concentration, but enzyme activity decreased. The apparent Km and Vmax values for
      methanol substrate of HP A16 MOX were 0.25 mM and 30 U/mg, respectively. The
      purified MOX enzyme was applied onto sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis; molecular weight of the enzyme was calculated to be about 670
      kDa. Each MOX enzyme is composed of eight identical subunits, each of whose
      molecular weight is around 82 kDa and which contain eight moles of FAD as the
      prosthetic group, and the pI of the natural enzyme is found to be 6.4. The
      purified MOX enzyme was used in the bioconversion of methanol to formaldehyde as
      a catalyst; this conversion was compared to the conversion percentages of whole
      cells in our previous article in terms of catalytic performances.

PMID- 16971304
TI  - Spherical vs. granular immobilization support selection and performance on an
      optical flow cell immunosensor based on the fluorescence of Cyanine-5.
AB  - A spherical porous glass support Trisoperl (TRISO) with four pore diameters (o
      47.8; 55.9; 102.6, and 108.8 nm) was characterized and selected for application
      in an optical flow cell immunosensor, in comparison with controlled pore glass
      (CPG). The TRISO support was functionalized with aldehyde and isothiocyanate (
      NCS) groups to attach bovine serum albumin and alkaline phosphatase (AP). The
      TRISO isothiocyanate pore diameter 47.8 nm (TRISO(-NCS) 47.8 nm) showed the
      better potential to be used in the immunosensor. It immobilized more protein
      (19.3 mg AP per g support) while presenting an optical performance comparable to
      the CPG. CPG(-NCS) and TRISO(-NCS) 47.8 nm were tested in the immunosensor model
      where the saturation of the Goat IgG immobilized in the supports with Monoclonal
      Anti-Goat IgG conjugated with Cyanine-5 was reached, followed by regeneration
      with the elution buffer modified PBS pH 2.0. The TRISO(-NCS) 47.8 nm presented
      lower fluorescence intensity at saturation (around 39 AU) than CPG(-NCS) (150 to
      104 AU), but revealed a major advantage related to the uniform arrangement of the
      spherical particles in the flow cell, generating no significant fluorescence
      differences between gravity and flow package.

PMID- 16971305
TI  - Efficient extraction of high-quality total RNA from various hop tissues (Humulus
      lupulus L.).
AB  - The isolation of high-quality RNA is a prerequisite for gene expression studies.
      RNA quality is of special relevance if PCR-based strategies such as cDNA-AFLP or
      RT-PCR are followed. Our molecular investigations of hop (Humulus lupulus L.)
      focus on genes that determine the biosynthesis of prenylflavonoids with
      interesting biological activities which accumulate in the lupulin glands.
      However, optimized protocols for RNA extraction from hop cones are not available.
      In this study, the RNeasy midi kit protocol was modified to isolate high amounts
      of total RNA from fresh and freeze-dried hop tissues, specifically leaves, female
      inflorescences, and lupulin-enriched hop cone fractions. The main difficulties in
      obtaining high RNA yields were related to specific features of hop, including the
      abundance of secondary metabolites and their accumulation in the sticky lupulin
      glands. The introduction of a number of modifications into the RNeasy midi kit
      protocol resulted in RNA of high quality, as assessed by spectrophotometry and
      electrophoresis in agarose gels. The protocol developed is currently being used
      to produce cDNA-AFLP fingerprints of hop cones and leaves for genetic screening.
      Furthermore, the method could provide RNA for further molecular studies,
      including Northern blot hybridizations and reverse transcription-polymerase chain
      reactions.

PMID- 16971306
TI  - Isolation and characterization of the P5 adhesin protein of Haemophilus parasuis
      serotype 5.
AB  - Haemophilus parasuis is a Gram-negative respiratory pathogen of young pigs that
      colonizes the upper respiratory tract and produces a number of symptoms
      collectiviely described as Glasser's disease. Recently, an H. parasuis P5-like
      outer membrane adhesin protein homologous to H. influenzae P5 was identified. The
      P5 adhesin was partially purified by anion exchange and size-exclusion
      chromatography. Final purification for functional studies was performed by
      elution of the protein from a polyacrylamide gel. Identification of the protein
      as a P5 adhesin homolog of H. influenzae was confirmed by N-terminal sequencing.
      The P5 protein had a molecular mass of 32,000 and a pI of 5.5. Unlike the H.
      influenzae P5 adhesin, the H. parasuis P5 protein did not bind carcinoembryonic
      antigen.

PMID- 16971307
TI  - One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones using CuBr2 as catalyst.
AB  - A simple, efficient procedure and improved conditions have been found to carry
      out the Biginelli reaction for the synthesis of 3,4-dihydropyrimidin-2(1H)-one
      derivatives. This synthesis was performed using CuBr2 as the catalyst in ethanol
      solution. The optimum conditions were as follows: the molar ratio of aldehyde to
      alpha,beta-diketone to urea or thiourea is 1:1:1:0.5, the molar ratio of catalyst
      to aldehyde is 25%, and the reaction time is 4 h. Under the above conditions, the
      highest yield of dihydropyrimidinones was up to 95%. Compared with the classical
      Biginelli reaction conditions, this new method has the advantage of excellent
      yields and short reaction times.

PMID- 16971311
TI  - Current and future treatment options for acne.
AB  - Acne is a frequent skin disease with abnormalities in the process of
      keratinization, sebaceous gland functioning and inflammation. In this review, our
      understanding of the pathogenesis of acne has been updated. An overview of
      efficacy and side effects of available anti-acne treatments is presented. Based
      on the present overview a recommendation for the treatment of various
      manifestations of acne is provided, also reconciling beneficial combinations of
      treatments. It is attractive to speculate that the increased insight into the
      pathogenesis of acne will create new treatment options. Challenging new options
      comprise blue light, photodynamic therapy, retinoic acid metabolism blocking
      agents and inhibitors of Th-1 cytokines.

PMID- 16971312
TI  - Zinc in skin pathology and care.
AB  - OBJECTIVES: To assess the significance of zinc in the etiology of various
      dermatological conditions and examine the role of zinc as a mode of treatment for
      a wide range of dermatoses. METHODS: Review of existing literature through
      searches using the PubMed site with zinc and the dermatosis in question as search
      words. RESULTS: Severe zinc deficiency states such as acrodermatitis
      enteropathica are associated with a variety of skin manifestations, such as
      perioral, acral and perineal dermatitis. These syndromes can be reversed with
      systemic zinc repletion. In addition to skin pathologies which are clearly zinc
      dependent, many dermatological conditions (e.g. dandruff, acne and diaper rash)
      have been associated and treated with zinc. Success rates for treatment with zinc
      vary depending on the disease, mode of application and zinc salt used. Usually,
      alternative modes of treatment are superior to zinc. CONCLUSIONS: Generally, it
      seems that with the exception of systemic deficiency states, there is very little
      evidence to convincingly demonstrate the efficacy of zinc as a first-line
      treatment for any dermatological conditions. Further research is needed in order
      to establish the indications for zinc treatment in dermatology, optimal mode of
      delivery, type of compound and therapeutic indexes.

PMID- 16971313
TI  - Hidradenitis suppurativa treated with dapsone: A case series of five patients.
AB  - OBJECTIVE: To evaluate the efficacy of dapsone in the treatment of hidradenitis
      suppurativa refractory to therapy with oral antibiotics and isotretinoin.
      METHODS: A retrospective review was performed of five patients treated with
      dapsone between 2002 and 2005. Clinical improvement and adverse events were
      recorded by the physician. Patients were asked to retrospectively rate their
      symptoms prior to and after starting dapsone. RESULTS: Improvement was noted in
      all five patients within 4-12 weeks at doses ranging between 25 and 150 mg/day.
      All patients required maintenance therapy with dapsone at doses between 50 and
      150 mg/day to sustain their disease control. Patient-reported symptoms improved
      in all cases after dapsone initiation, supporting physician observed clinical
      improvement. Treatment was well tolerated in all patients with no significant
      adverse effects noted. The median follow-up period was 24 months. CONCLUSION:
      Dapsone appears to be an effective and safe alternative therapeutic option for
      hidradenitis suppurativa and may be particularly useful for women in the
      reproductive age group.

PMID- 16971314
TI  - Is it necessary to have routine blood tests in patients treated with
      isotretinoin?
AB  - OBJECTIVES: Several side effects can be observed from isotretinoin use, which has
      been used in acne therapy for years. In this study, the side effects of
      isotretinoin on skin and mucosa, blood test changes and their relation with total
      dose were investigated in patients who used equal doses of isotretinoin.
      MATERIALS AND METHODS: A total of 91 outpatients with acne vulgaris (57 females
      and 34 males; age range 17-28 years, mean 21+/-2.19 years) were enrolled in this
      study. Skin and mucosal findings and pre- and post-treatment blood tests and
      their correlation with the total dose were investigated. Student's t-test and the
      Mann-Whitney U-test were used in the statistical analyses. RESULTS: In all, 89
      out of 91 patients completed the study. Cholesterol (p = 0.00), triglyceride (p =
      0.00) and low density lipoprotein (LDL) (p = 0.001) levels were found to be
      significantly elevated. But these values were not over the double of the upper
      limits. No correlations were found among the total dose and the skin and mucosal
      changes as well as the blood test results. CONCLUSION: It is concluded that
      examination of cholesterol, triglyceride and LDL-cholesterol should be performed
      monthly if the initial blood tests are close to the upper limits; otherwise,
      examinations at 2- or 3-month intervals are sufficient, which would save
      unnecessary costs.

PMID- 16971315
TI  - Azithromycin versus tetracycline in the treatment of acne vulgaris.
AB  - BACKGROUND: Acne vulgaris affects a large number of young adults and often
      presents with facial and truncal involvement. Systemic antibiotics are used for
      the treatment of papulopustular and cystic lesions. OBJECTIVE: We sought to
      determine the efficacy and safety of azithromycin versus tetracycline in the
      treatment of acne vulgaris. METHODS: A randomized, investigator-blind, clinical
      trial was carried out for 3 months at the outpatient clinic of Emam Khomeini
      University Hospital, Ahwaz, Iran. A total of 290 patients with moderate to severe
      papulopustular acne vulgaris were allocated to two groups, azithromycin and
      tetracycline, for 3 months of treatment. Azithromycin 500 mg was prescribed for 3
      consecutive days a week for 1 month and then 250 mg every other day for the
      following 2 months. Tetracycline 1 g was similarly prescribed: daily for 1 month
      and then 500 mg daily for the following 2 months. RESULTS: Both antibiotics were
      effective in reducing inflammatory lesions and improving acne. Azithromycin
      produced a slightly higher percentage of improvement compared with tetracycline
      (100 cases/84.7% vs 94 cases/79.7%). CONCLUSION: Azithromycin is a safe and
      effective alternative in the treatment of inflammatory acne.

PMID- 16971316
TI  - The bacterial flora of the skin surface following routine MAL-PDT.
AB  - Photodynamic therapy using methylated 5-aminolevulate (MAL-PDT) appears to have
      an effect on non-neoplastic skin diseases, for example acne vulgaris and rosacea,
      for which antibiotics are sometimes used, and a possible antibiotic effect of PDT
      has previously been suggested. It does, however, also cause local
      immunosuppression and post-treatment barrier defects, which may promote
      infection. At the same time, PDT-induced therapeutic skin damage is sometimes
      confused with secondary bacterial infection by non-dermatologists. The possible
      changes in bacterial flora associated with MAL-PDT were therefore studied in 47
      patients undergoing treatment. Skin swabs were taken immediately before applying
      the MAL and instantly after light irradiation. Bacterial growth was identified in
      18 cases. No statistically significant changes were seen, either in the specific
      species found or the estimated bacterial density on the skin surface. The
      observations do not support the notion that routine MAL-PDT affects the bacterial
      flora of the skin in a clinically significant manner. Therefore, the possible
      antibacterial effect of routine MAL-PDT is probably not the main explanation of
      its apparent effect on non-neoplastic skin disease.

PMID- 16971317
TI  - How much of a topical agent should be prescribed for children of different sizes?
AB  - BACKGROUND: Compared with guidelines for the quantity of topical corticosteroids
      to apply in adults, standards for the use of topical corticosteroids in children
      are not well described. OBJECTIVE: To devise simple-to-use guidelines for topical
      corticosteroid quantities needed in infants, children, pre-teens, and adults.
      METHODS: We determined body surface area (BSA) using mean heights and weights in
      order to calculate the appropriate quantities of medication to be prescribed.
      RESULTS: As a rough estimate, infants require one-fifth of adult doses, children
      two-fifths of adult doses, and adolescents two-thirds of adult doses. However,
      the assessment of BSA may vary considerably between clinicians. Patients may also
      vary in how thickly they apply topical medication. CONCLUSIONS: A simple
      guideline for how much topical corticosteroid to prescribe may facilitate the
      treatment of young children with skin disease.

PMID- 16971318
TI  - Abatacept: A review of a new biologic agent for refractory rheumatoid arthritis
      for dermatologists.
AB  - Abatacept is a newly approved treatment for rheumatoid arthritis refractory to
      other agents. Abatacept is a fusion protein of the cytotoxic T-lymphocyte antigen
      (CTLA) molecule and immunoglobulin (Ig) G1 that blocks CD28. Specifically,
      abatacept blocks the CD80 and CD86 ligands on the surface of antigen-presenting
      cells that must interface with the T-cell's CD28 receptor to activate T cells.
      Abatacept seems to be more immunosuppressive than tumor necrosis factor alpha
      blockers. The combination of abatacept and a tumor necrosis factor alpha blocking
      agent does not seem more effective than either agent alone. Because abatacept has
      the ability to suppress T-cell function, it has the potential to be a treatment
      for psoriasis and other autoimmune conditions involving pathologic processes
      driven by T cells.

PMID- 16971319
TI  - Determination of the sildenafil effect on alopecia areata in childhood: An open
      pilot comparison study.
AB  - BACKGROUND: Alopecia areata is an immunologically mediated cessation of hair
      growth primarily involving, but not limited to, the scalp. The treatment of
      alopecia areata involves promotion of hair growth (for instance with topical
      minoxidil application), immunosuppression (intralesional or systemic steroid
      therapy, phototherapy) or immunomodulation (anthralin, dinitrochlorobenzene,
      diphenylcyclopropenone, squaric acid dibutylester). All these medications have
      some disadvantages and difficulties for the treatment of children with alopecia
      areata. OBJECTIVE: To use an open-pilot study to assess the efficacy of topical
      1% sildenafil in children diagnosed with alopecia areata. METHODS: Eight patients
      with (25% of scalp surface area involvement) alopecia areata who were refractory
      to previous topical treatments applied 1% sildenafil twice daily for 3 months.
      All the patients completed the study. RESULTS: Two patients experienced vellus
      type hair growth and one patient had terminal hair growth. However, these
      outcomes were accepted as the spontaneous regression of the disease. CONCLUSION:
      We cannot recommend the use of topical 1% sildenafil for the treatment of
      alopecia areata without further evidence of its therapeutic benefit.

PMID- 16971320
TI  - Granuloma faciale: Is it a new indication for pimecrolimus? A case report.
AB  - Granuloma faciale is a benign, chronic disease which is characterized by red
      brown facial nodules and plaques. This quite rare disease is mostly seen in
      middle-aged males. A 41-year-old female patient consulted our department with a
      facial lesion of 4 years' duration. A dermatological examination revealed a pink
      brown plaque of 1x5 cm over the nasal dorsum extending to the left malar region.
      Her personal and family histories were unremarkable. The routine hemogram and
      biochemical tests were normal, antinuclear antibody was negative. In the
      histopathological examination of the biopsy material which was taken from the
      lesion, the epidermis was intact; grenz zone was observed in the papillary dermis
      and with diffuse infiltrate with leukocytoclastic vasculitis and eosinophils,
      polymorphonuclear leukocytes and lymphocytes in the dermis were observed. With
      these findings, the patient was diagnosed with granuloma faciale and treatment
      with topical pimecrolimus cream 1% was started. The patient applied this
      treatment twice a day for 2 months and a dramatic recovery was observed after
      this period. The case is discussed in comparison with the literature.

PMID- 16971321
TI  - Xeroderma pigmentosum and lentigo maligna in identical twins.
AB  - Xeroderma pigmentosum (XP) is a rare autosomal recessive genodermatosis. Skin
      abnormalities result from an inability to repair UV-damaged DNA. Clinically, XP
      presents with early onset cutaneous changes (severe photosensitivity, actinic
      keratoses, and telangiectasias) and an increase of developing cutaneous
      malignancies beginning in early childhood, but lentigo maligna and melanomas are
      relatively rare. Here we report on homozygote twins in whom there was no positive
      family history. They showed subnormal physical growth. On ophthalmological
      examination, both had photophobia and decreased visual acuity. Since birth,
      several excisions had been performed for skin neoplasms. In one of them a
      pigmented patch developed over the frontal area which proved to be lentigo
      maligna and she was referred to a dermato-oncology center. They have been given
      isotretinoin and physical sunscreen since then. The follow-up period was extended
      to 2 years and no serious complications occurred from the above treatment. This
      is an interesting report about XP in twins with the presentation of the rare
      neoplasm lentigo maligna.

PMID- 16971322
TI  - Pemphigus foliaceus induced by radiotherapy and responsive to dapsone.
AB  - Pemphigus foliaceus induced by ionizing radiation therapy is a rare condition. We
      describe the case of a 70-year-old female who developed pemphigus foliaceus after
      X-ray treatment for an adenocarcinoma of the left breast. The eruption started at
      the portal of irradiation and only subsequently spread to other cutaneous areas.
      Mucosal membranes were not affected. Skin lesions were completely responsive to
      dapsone therapy.

PMID- 16971323
TI  - Treatment of pyogenic granulomas with the Nd-YAG laser.
AB  - Pyogenic granuloma is a common vascular tumour that can be treated by various
      means. However, some large lesions and those located on some difficult-to-treat
      body sites may represent a difficult challenge to the clinician (residual pain
      after treatment, difficult to cover with a dressing, or risk of sequelae). We
      report the successful treatment of such lesions in three patients using the Nd
      YAG laser.

PMID- 16971325
TI  - Antibiotic resistance is on the rise. Should dermatologists be concerned?

PMID- 16971324
TI  - Botulinum toxin A treatment for contouring of the lower leg.
AB  - BACKGROUND: Botulinum toxin type A is widely used in the treatment of bilateral
      masseteric hypertrophy in Asians. Botulinum toxin A may have plausible effects on
      the oversized calf muscles that cause mental distress in Korean women. OBJECTIVE:
      We report our successful use of botulinum toxin A in the treatment of two
      patients with muscular legs. METHODS: The toxin was injected into the
      gastrocnemius muscle, 300-360 U per side. RESULTS: A reduction in calf
      circumference was noticed 3 weeks after treatment and was maintained for 6-8
      months without systemic side effects. CONCLUSION: Botulinum toxin treatment for
      enlarged gastrocnemius muscles is a non-invasive alternative method for the
      improvement of calf contours.

PMID- 16971328
TI  - Challenges in tissue engineering.
AB  - Almost 30 years have passed since a term 'tissue engineering' was created to
      represent a new concept that focuses on regeneration of neotissues from cells
      with the support of biomaterials and growth factors. This interdisciplinary
      engineering has attracted much attention as a new therapeutic means that may
      overcome the drawbacks involved in the current artificial organs and organ
      transplantation that have been also aiming at replacing lost or severely damaged
      tissues or organs. However, the tissues regenerated by this tissue engineering
      and widely applied to patients are still very limited, including skin, bone,
      cartilage, capillary and periodontal tissues. What are the reasons for such slow
      advances in clinical applications of tissue engineering? This article gives the
      brief overview on the current tissue engineering, covering the fundamentals and
      applications. The fundamentals of tissue engineering involve the cell sources,
      scaffolds for cell expansion and differentiation and carriers for growth factors.
      Animal and human trials are the major part of the applications. Based on these
      results, some critical problems to be resolved for the advances of tissue
      engineering are addressed from the engineering point of view, emphasizing the
      close collaboration between medical doctors and biomaterials scientists.

PMID- 16971329
TI  - Systems interface biology.
AB  - The field of systems biology has attracted the attention of biologists,
      engineers, mathematicians, physicists, chemists and others in an endeavour to
      create systems-level understanding of complex biological networks. In particular,
      systems engineering methods are finding unique opportunities in characterizing
      the rich behaviour exhibited by biological systems. In the same manner, these new
      classes of biological problems are motivating novel developments in theoretical
      systems approaches. Hence, the interface between systems and biology is of mutual
      benefit to both disciplines.

PMID- 16971330
TI  - The role of modelling in identifying drug targets for diseases of the cell cycle.
AB  - The cell cycle is implicated in diseases that are the leading cause of mortality
      and morbidity in the developed world. Until recently, the search for drug targets
      has focused on relatively small parts of the regulatory network under the
      assumption that key events can be controlled by targeting single pathways. This
      is valid provided the impact of couplings to the wider scale context of the
      network can be ignored. The resulting depth of study has revealed many new
      insights; however, these have been won at the expense of breadth and a proper
      understanding of the consequences of links between the different parts of the
      network. Since it is now becoming clear that these early assumptions may not hold
      and successful treatments are likely to employ drugs that simultaneously target a
      number of different sites in the regulatory network, it is timely to redress this
      imbalance. However, the substantial increase in complexity presents new
      challenges and necessitates parallel theoretical and experimental approaches. We
      review the current status of theoretical models for the cell cycle in light of
      these new challenges. Many of the existing approaches are not sufficiently
      comprehensive to simultaneously incorporate the required extent of couplings.
      Where more appropriate levels of complexity are incorporated, the models are
      difficult to link directly to currently available data. Further progress requires
      a better integration of experiment and theory. New kinds of data are required
      that are quantitative, have a higher temporal resolution and that allow
      simultaneous quantitative comparison of the concentration of larger numbers of
      different proteins. More comprehensive models are required and must accommodate
      not only substantial uncertainties in the structure and kinetic parameters of the
      networks, but also high levels of ignorance. The most recent results relating
      network complexity to robustness of the dynamics provide clues that suggest
      progress is possible.

PMID- 16971331
TI  - Tyrosine-derived polycarbonate membrane in treating mandibular bone defects. An
      experimental study.
AB  - This study was designed to evaluate the suitability of a novel bioabsorbable
      material in treating bone defects. A poly(desaminotyrosyl-tyrosine-ethyl ester
      carbonate) (PDTE carbonate) membrane (thickness 0.2-0.3 mm) was implanted into
      the mandibular angle of 20 New Zealand White rabbits to cover a through-and
      through defect (12 x 6 mm). In group 1, the defects were left unfilled but
      covered with membrane and in group 2 the defects were filled with bioactive glass
      mesh and covered with membrane, too. Controls were left uncovered and unfilled.
      The animals were followed for 6, 12, 24 and 52 weeks, respectively. The material
      was evaluated by qualitative analysis of histological reactions and newly formed
      bone. We found that PDTE carbonate elicited a modest foreign body reaction in the
      tissues, which was uniform throughout the study. New bone formation was seen in
      all samples after six weeks. Group 1 had more new bone formation until 24 weeks
      and after this the difference settled. Based on findings of this study it was
      concluded that PDTE carbonate membranes have good biocompatibility and are
      sufficient to enhance bone growth without additional supportive matrix.

PMID- 16971332
TI  - Monitoring of metabolite gradients in tissue-engineered constructs.
AB  - At present, the assessment of developing tissue-engineered constructs is almost
      always carried out destructively using biochemical or histological methods to
      determine cell number, viability and tissue growth throughout the construct.
      Since many of these experiments are long, taking weeks or even months to
      complete, simple and readily applicable non-destructive methods of monitoring
      changes in cell metabolism, viability and tissue deposition within the construct
      would be invaluable; such methods could point out adverse responses during the
      early stages of culture. Here, we describe the use of microdialysis for detecting
      local changes in cellular metabolism within a tissue-engineered construct. Three
      dimensional constructs consisting of bovine articular chondrocytes entrapped in
      an alginate gel were cultured in a bioreactor for two weeks. Glucose and lactate
      were monitored by microdialysis, as the major nutrient and metabolite,
      respectively. Concentration gradients within the construct were evident, with the
      highest lactate concentrations in the construct centre. The local lactate
      concentration was a measure of cellular metabolic activity, decreasing as
      cellular activity fell and increasing as cellular activity was stimulated.
      Nutrient starvation and cell death in the construct centre could be readily
      detected in constructs deliberately cultured under adverse conditions. The
      results show that probe measurements can give an early warning of inappropriate
      local metabolic changes. Such information during the growth of tissue-engineered
      constructs would allow either corrective action or else an early end to an
      unsuccessful test.

PMID- 16971333
TI  - Fifty years later: A neurodynamic explanation of Fitts' law.
AB  - An intrinsic property of human motor behaviour is a trade-off between speed and
      accuracy. This is classically described by Fitts' law, a model derived by
      assuming the human body has a limited capacity to transmit information in
      organizing motor behaviour. Here, we propose an alternative foundation, based on
      the neurodynamics of the motor circuit, wherein Fitts' law is an approximation to
      a more general relationship. In this formulation, widely observed inconsistencies
      with experimental data are a consequence of psychomotor delay. The methodology
      developed additionally provides a method to estimate the delay within the motor
      circuit from the speed-accuracy trade-off alone.

PMID- 16971334
TI  - The relevance of nonlinear stacking interactions in simple models of double
      stranded DNA.
AB  - Single molecule DNA experiments provide interesting data that allow a better
      understanding of the mechanical interactions between the strands and the
      nucleotides of this molecule. In some sense, these experiments complement the
      classical ones about DNA thermal denaturation. It is well known that the original
      Peyrard-Bishop (PB) model by means of a harmonic stacking potential and a
      nonlinear substrate potential has been able to predict the existence of a
      critical temperature of full denaturation of the molecule. In the present paper,
      driven by the findings of single molecule experiments, we substitute the original
      harmonic intra-strand stacking potential with a Duffing type potential. By
      elementary and analytical arguments, we show that with this choice it is possible
      to obtain a sharp transition in the classical domain wall solution of the PB
      model and the compactification of the classical solitary wave solutions of other
      models for the dynamics of DNA. We discuss why these solutions may improve our
      knowledge of the DNA dynamics in several directions.

PMID- 16971335
TI  - The network of sheep movements within Great Britain: Network properties and their
      implications for infectious disease spread.
AB  - During the 2001 foot and mouth disease epidemic in the UK, initial dissemination
      of the disease to widespread geographical regions was attributed to livestock
      movement, especially of sheep. In response, recording schemes to provide accurate
      data describing the movement of large livestock in Great Britain (GB) were
      introduced. Using these data, we reconstruct directed contact networks within the
      sheep industry and identify key epidemiological properties of these networks.
      There is clear seasonality in sheep movements, with a peak of intense activity in
      August and September and an associated high risk of a large epidemic. The high
      correlation between the in and out degree of nodes favours disease transmission.
      However, the contact networks were largely dissasortative: highly connected nodes
      mostly connect to nodes with few contacts, effectively slowing the spread of
      disease. This is a result of bipartite-like network properties, with most links
      occurring between highly active markets and less active farms. When comparing
      sheep movement networks (SMNs) to randomly generated networks with the same
      number of nodes and node degrees, despite structural differences (such as
      disassortativity and higher frequency of even path lengths in the SMNs), the
      characteristic path lengths within the SMNs are close to values computed from the
      corresponding random networks, showing that SMNs have 'small-world'-like
      properties. Using the network properties, we show that targeted biosecurity or
      surveillance at highly connected nodes would be highly effective in preventing a
      large and widespread epidemic.

PMID- 16971336
TI  - In silico evolution of functional morphology: A test on bone tissue biomechanics.
AB  - Evolutionary algorithms (EAs) use Darwinian principles--selection among random
      variation and heredity--to find solutions to complex problems. Mostly used in
      engineering, EAs gain growing interest in ecology and genetics. Here, we assess
      their usefulness in functional morphology, introducing finite element modelling
      (FEM) as a simulated mechanical environment for evaluating the 'fitness' of
      randomly varying structures. We used this method to identify biomechanical
      adaptations in bone tissue, a long-lasting problem in skeletal morphology. The
      algorithm started with a bone tissue model containing randomly distributed
      vascular spaces. The EA randomly mutated the distribution of vascular spaces, and
      selected the new structure if its mechanical resistance was increased. After some
      thousands of generations, organized phenotypes emerged, containing vascular
      canals and sinuses, mimicking real bone tissue organizations. This supported the
      hypothesis that natural bone microstructures can result from biomechanical
      adaptation. Despite its limited faithfulness to reality, we discuss the ability
      of the EA+FEM method to assess adaptation in a dynamic evolutionary framework,
      which is not possible in the real world because of the generation times of macro
      organisms. We also point out the interesting potential of EAs to simulate not
      only adaptation, but also concurrent evolutionary phenomenons such as historical
      contingency.

PMID- 16971337
TI  - Wet but not slippery: Boundary friction in tree frog adhesive toe pads.
AB  - Tree frogs are remarkable for their capacity to cling to smooth surfaces using
      large toe pads. The adhesive skin of tree frog toe pads is characterized by peg
      studded hexagonal cells separated by deep channels into which mucus glands open.
      The pads are completely wetted with watery mucus, which led previous authors to
      suggest that attachment is solely due to capillary and viscous forces generated
      by the fluid-filled joint between the pad and the substrate. Here, we present
      evidence from single-toe force measurements, laser tweezer microrheometry of pad
      mucus and interference reflection microscopy of the contact zone in Litoria
      caerulea, that tree frog attachment forces are significantly enhanced by close
      contacts and boundary friction between the pad epidermis and the substrate,
      facilitated by the highly regular pad microstructure.

PMID- 16971338
TI  - Modelling dynamics of the type I interferon response to in vitro viral infection.
AB  - Innate immunity is crucial in the early stages of resistance to novel viral
      infection. The family of cytokines known as the interferons (IFNs) forms an
      essential component of this system: they are responsible for signalling that an
      infection is underway and for promoting an antiviral response in susceptible
      cells. We construct a spatial stochastic model, parameterized by experimental
      data and informed by analytic approximation, to capture the dynamics of virus-IFN
      interaction during in vitro infection of Madin-Darby bovine kidney cell
      monolayers by Herpes simplex virus 1. The dose dependence of infection
      progression, subsequent monolayer destruction and IFN-beta production are
      investigated. Implications for in vivo infections, in particular the priming of
      susceptible cells by IFN-beta during infection, are considered.

PMID- 16971339
TI  - Modelling protein-protein interaction networks via a stickiness index.
AB  - What type of connectivity structure are we seeing in protein-protein interaction
      networks? A number of random graph models have been mooted. After fitting model
      parameters to real data, the models can be judged by their success in reproducing
      key network properties. Here, we propose a very simple random graph model that
      inserts a connection according to the degree, or 'stickiness', of the two
      proteins involved. This model can be regarded as a testable distillation of more
      sophisticated versions that attempt to account for the presence of interaction
      surfaces or binding domains. By computing a range of network similarity measures,
      including relative graphlet frequency distance, we find that our model
      outperforms other random graph classes. In particular, we show that given the
      underlying degree information, fitting a stickiness model produces better results
      than simply choosing a degree-matching graph uniformly at random. Therefore, the
      results lend support to the basic modelling methodology.

PMID- 16971340
TI  - Transesterification of p-hydroxybenzoate esters (parabens) by human intestinal
      (Caco-2) cells.
AB  - p-Hydroxybenzoate ester (paraben) preservatives are used in numerous orally
      administered products. The recognized route of metabolism for parabens is
      hydrolysis to p-hydroxybenzoic acid followed by conjugation and excretion.
      However, in the presence of alcohols, a presystemic transesterification pathway
      not previously reported for the human intestine can occur. Using human intestinal
      (Caco-2) cells, it was observed that hydrolysis of parabens to p-hydroxybenzoic
      acid is reduced markedly by ethanol concentrations that can occur in the human
      intestine, 0.25-0.5% (v/v). Ethanol concentrations of 1.0-2.5% (v/v) were optimal
      for transesterification to ethylparaben in Caco-2 cell homogenates. The kinetics
      of the transesterification reaction with regard to ethanol concentration (0-20%),
      time, pH (3-9), protein concentration (1-5 mg ml-1) and substrate concentration
      (6.25-200 microM) as well as the effects of different alcohols were studied. The
      Km and Vmax values for transesterification with ethanol for methyl, propyl,
      butyl, heptyl and octyl parabens were 449.7, 165.7, 86.1, 24.2 and 45.9 microM
      and 114.4, 37.5, 19.5, 7.5 and 7.6 micromol h-1 mg-1 Caco-2 cell protein,
      respectively. The Vmax values for transesterification of methylparaben with
      ethanol, propan-1-ol, butan-1-ol were 114.4, 5.1 and 4.9 micromol h-1 mg-1,
      respectively. Collectively, the kinetic data demonstrate that the enzyme
      responsible for the transesterification reaction has a preference for short-chain
      esters and represents the first report of transesterification in human intestinal
      cells. An implication of this mechanism is that alcohol-containing in vitro
      biosystems or protocols for the study of parabens disposition could generate
      transesterified artefacts. The clinical or toxicological implication is that,
      following co-ingestion of ester compounds with ethanol, transesterification could
      provide the basis for a previously unrecognized drug-alcohol interaction.

PMID- 16971341
TI  - Biotransformation and pharmacokinetics of the antiplasmodial naphthylisoquinoline
      alkaloid dioncophylline A.
AB  - The biotransformation of the antiplasmodial naphthylisoquinoline alkaloid
      dioncophylline A by rat liver microsomes and its pharmacokinetics in male rats
      were studied. Incubation of dioncophylline A with rat liver microsomes resulted
      in the formation of the major metabolite 5'-O-demethyldioncophylline A, and a
      second minor metabolite, corresponding to the mass of an as yet unknown 4
      hydroxydioncophylline A. Kinetic constants of the formation of 5'-O
      demethyldioncophylline A were Km = 32 nmol and Vmax = 20 pmol min-1 mg-1).
      Administration of dioncophylline A at a dose of 6.67 mg kg-1 body weight to rats
      intravenously and orally (n = 4 per group) resulted in peak plasma levels of 0.84
      and 0.11 microg ml-1, respectively. Levels of metabolites were below the limit of
      quantitation (LOQ). The following pharmacokinetic parameters of dioncophylline A
      were determined: oral bioavailability of 25%, plasma half-life of 2.5 h and
      partition volume of 8 l kg-1 body weight. Concentrations of dioncophylline A
      metabolites in all plasma and urine samples were below the limit of detection
      (LOD) and recovery of dioncophylline A in urine was very low, suggesting
      distribution into lipid rich tissues.

PMID- 16971342
TI  - Metabolism of N-substituted 7-methoxy-4-(aminomethyl) -coumarins by cytochrome
      P450 2D6 mutants and the indication of additional substrate interaction points.
AB  - Previous studies have shown the critical roles residues F120 and F483 play in the
      oxidative metabolism of 7-methoxy-4-(aminomethyl)-coumarin (MAMC) by cytochrome
      P450 2D6 (CYP2D6). In the present study, a series of N-alkyl-7-methoxy-4
      (aminomethyl)-coumarins (MAMC analogues) were used as substrates for the F120A
      and F483A mutants in order to probe the CYP2D6 active site. The F120A and F483A
      mutants of CYP2D6 displayed significant activity towards the MAMC analogues.
      Automated docking studies of the MAMC analogues in a CYP2D6 homology model
      suggested a distal hydrophobic active site binding cleft for the substrate N
      alkyl chains, consisting of the residues L213 and V308.

PMID- 16971343
TI  - Metabolism of new-generation taxanes in human, pig, minipig and rat liver
      microsomes.
AB  - The novel taxanes SB-T-1102, SB-T-1214 and SB-T-1216 are up to 1000-fold more
      cytotoxic for resistant tumour cells than clinically used paclitaxel and
      docetaxel, and the current study has examined the metabolism of these new taxanes
      in human, rat, pig and minipig liver microsomes. Metabolites were characterized
      by high-performance liquid chromatography (HPLC)/tandem mass spectrometry (MS/MS)
      analysis. Metabolic pathways derived from their structures were confirmed by
      investigating subsequent metabolism of purified metabolites. SB-T-1102, SB-T-1214
      and SB-T-1216 were metabolized to 14, 10 and 11 products, respectively. In
      contrast to docetaxel, side-chain hydroxylation did not occur at their tert-butyl
      group, but on the isobutyl (SB-T-1102) or isobutenyl (SB-T-1214 and SB-T-1216)
      chains. Species differences in their metabolism were observed. For example, human
      and untreated rat microsomes hydroxylated SB-T-1216 preferentially at the side
      chain, whereas pig and minipig microsomes preferentially metabolized more at the
      taxane core. The increased formation of secondary and tertiary metabolites in rat
      microsomes with high expression of CYP3A1/2 compared with uninduced rats
      confirmed the role of CYP3A in taxane metabolism. All major products were formed
      by human cDNA-expressed CYP3A4 and none by CYP1A2, 1B1, 2A6, 2C9 and 2E1,
      indicating the principal role of CYP3A orthologues in SB-T metabolism. The
      knowledge of metabolic pathways of the examined agents and of their rates of
      formation is important due to possible metabolic inactivation of these three
      novel drugs with a great potential for the therapy of taxane-resistant tumours.
      The relatively slow metabolism of SB-T-1102 could be favourable for its
      antitumour efficiency in vivo.

PMID- 16971344
TI  - Metabolism of myclobutanil and triadimefon by human and rat cytochrome P450
      enzymes and liver microsomes.
AB  - Metabolism of two triazole-containing antifungal azoles was studied using
      expressed human and rat cytochrome P450s (CYP) and liver microsomes. Substrate
      depletion methods were used due to the complex array of metabolites produced from
      myclobutanil and triadimefon. Myclobutanil was metabolized more rapidly than
      triadimefon, which is consistent with metabolism of the n-butyl side-chain in the
      former and the t-butyl group in the latter compound. Human and rat CYP2C and
      CYP3A enzymes were the most active. Metabolism was similar in microsomes prepared
      from livers of control and low-dose rats. High-dose (115 mg kg-1 day-1 of
      triadimefon or 150 mg kg-1 day-1 of myclobutanil) rats showed increased liver
      weight, induction of total CYP, and increased metabolism of the two triazoles,
      though the apparent Km appeared unchanged relative to the control. These data
      identify CYP enzymes important for the metabolization of these two triazoles.
      Estimated hepatic clearances suggest that CYP induction may have limited impact
      in vivo.

PMID- 16971345
TI  - Disposition and metabolism of almotriptan in rats, dogs and monkeys.
AB  - Almotriptan is a new highly potent selective 5-HT1B/1D receptor agonist developed
      for the treatment of migraine, and the disposition of almotriptan in different
      animal species is now addressed in the current study. Almotriptan was well
      absorbed in rats (69.1%) and dogs (100%) following oral treatment. The absolute
      bioavailability was variable reflecting different degrees of absorption and first
      pass metabolism (18.7-79.6%). The elimination half-life was short and ranged
      between 0.7 and 3 h. The main route of elimination of almotriptan was urine with
      75.6% and 80.4% of the dose recovered over a 168-h period in rats and dogs,
      respectively. The gamma-aminobutyric acid metabolite formed by oxidation of the
      pyrrolidine ring was the main metabolite found in urine, faeces, bile, and plasma
      of rats and in monkey urine. By contrast, the unchanged drug, the indole acetic
      acid metabolite formed by oxidative deamination of the dimethylaminoethyl group,
      and the N-oxide metabolite were the main metabolites in dog.

PMID- 16971346
TI  - Disposition of 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE153) and its
      interaction with other polybrominated diphenyl ethers (PBDEs) in rodents.
AB  - The disposition of the 14C-labelled polybrominated diphenyl ether (PBDE)
      2,2',4,4',5,5'-hexaBDE (BDE153) was investigated in rodents following single and
      multiple doses and in a mixture with radiolabelled 2,2',4,4'-tetraBDE (BDE47) and
      2,2',4,4',5-pentaBDE (BDE99). In single exposure studies there was little or no
      effect of dose on BDE153 disposition in male rats in the range 1-100 micromol kg
      1. No major sex or species differences in the in vivo fate of BDE153 were
      detected. BDE153 was absorbed in rats or mice following gavage by approximately
      70%; retained in tissues; and poorly metabolized and slowly excreted. Mixture
      studies indicated that, relative to each other, more BDE47 was distributed to
      adipose tissue, more BDE153 accumulated in the liver, and BDE99 was metabolized
      to the greatest extent. BDE153 was probably retained in the liver due to minimal
      metabolism and elimination after 'first-pass' distribution to the tissue
      following gavage.

PMID- 16971347
TI  - Influence of cholestyramine on the pharmacokinetics of rosiglitazone and its
      metabolite, desmethylrosiglitazone, after oral and intravenous dosing of
      rosiglitazone: impact on oral bioavailability, absorption, and metabolic
      disposition in rats.
AB  - The possible influence of the bile acid-sequestering agent cholestyramine (CSA),
      which is a basic co-medication in hypercholesterolemic patients, on the
      pharmacokinetics of rosiglitazone (RGL) and its circulating metabolite
      desmethylrosiglitazone (DMRGL) was investigated following a single oral and
      intravenous dose of RGL to Wistar rats. The pharmacokinetic parameters of RGL and
      DMRGL were evaluated following oral or intravenous administration of RGL to rats
      at 10 mg kg-1 with and without pre-treatment (0.5 h before RGL administration) of
      CSA at 0.057, 0.115, 0.23 and 0.34 g kg-1 doses. With an increase in CSA dose
      there was dose-dependent decrease in area under the curve (AUC)(0-infinity) and
      Cmax with no change in Tmax, Kel and t1/2 values for both RGL and DMRGL following
      oral administration of RGL. The oral bioavailability of RGL was reduced by 19.9,
      35.6, 53.8 and 72.0% in rats following pre-treatment with CSA at 0.057, 0.115,
      0.230 and 0.340 g kg-1, respectively. There was no change in the above-mentioned
      pharmacokinetic parameters for RGL and DMRGL in rats when RGL was given
      intravenously following pre-treatment with the above-mentioned oral doses of CSA.
      Another objective of the study was to determine the effect of staggered oral CSA
      dosing at 1, 2 and 4 h after oral RGL administration at 10 mg kg-1. AUC(0
      infinity) of RGL and DMRGL was reduced following CSA staggered administration at
      1 h, whereas 2- and 4-h staggered dose administration of CSA had no effect on the
      AUC(0-infinity) of RGL and DMRGL. Irrespective of CSA staggered dose
      administration there was no change in other pharmacokinetic parameters, namely
      Cmax, Tmax, Kel and t1/2. The apparent formation rate constant (Kf) of DMRGL was
      also calculated to show that only the absorption of RGL was affected, not the
      apparent formation rate of DMRGL. The authors also studied the in vitro
      adsorption of RGL (100, 250, 500 microg ml-1) at various pH conditions (pH 2, 4
      and 7) and different concentrations of CSA (15, 30, 60 and 120 mg ml-1). The
      percentage binding of CSA was in the range 50-72% (at pH 2), 74-89% (at pH 4) and
      97-100% (at pH 7). In conclusion, we carried out a systematic investigation
      demonstrating mechanistically the interaction potential of RGL when co
      administered with CSA. The applicability of the metabolite data after intravenous
      and oral dosing and pH-based binding experiments further adds credence to the key
      findings.

PMID- 16971348
TI  - Ultrastructural changes of mitochondria in the cultivated skin fibroblasts of
      patients with point mutations in mitochondrial DNA.
AB  - Mitochondrial disorders represent a heterogeneous group of multisystem diseases
      with extreme variability in clinical phenotype. The diagnosis of mitochondrial
      disorders relies heavily on extensive biochemical and molecular analyses combined
      with morphological studies including electron microscopy. Although muscle is the
      tissue of choice for electron microscopic studies, the authors investigated
      cultivated human skin fibroblasts (HSF) harboring 3 different pathologic mtDNA
      mutations: 3243A > G, 8344A > G, 8993T > G. They addressed to the possibility of
      whether mtDNA mutations influence mitochondrial morphology in HSF and if
      ultrastructural changes of mitochondria may be used for differential diagnostics
      of mitochondrial disorders caused by mtDNA mutations. Ultrastructural analysis of
      patients' HSF revealed a heterogeneous mixture of mainly abnormal, partially
      swelling mitochondria with unusual and sparse cristae. The most characteristic
      cristal abnormalities were heterogeneity in size and shapes or their absence.
      Typical filamentous and branched mitochondria with numerous cristae as appeared
      in control HSF were almost not observed. In all lines of cultured HSF with
      various mtDNA mutations, similar ultrastructural abnormalities and severely
      changed mitochondrial interior were found, although no alterations in function
      and amount of OXPHOS were detected by routinely used biochemical methods in two
      lines of cultured HSF. This highlights the importance of morphological analysis,
      even in cultured fibroblasts, in diagnostics of mitochondrial disorders.

PMID- 16971349
TI  - The "oil well analogy" as a comprehensive interpretation of factors leading to
      muscle injury and wasting.
AB  - Muscle abnormalities involved in chronic obstructive pulmonary disease (COPD) or
      the changes leading to muscle wasting and cachexia in neoplastic patients have a
      remarkable clinical impact, but their study is complex and findings are sometimes
      paradoxical. In this review, the main factors influencing muscle wasting and
      muscle abnormalities found in chronic diseases such as COPD are regarded in the
      light of a comprehensive approach. All this changes work in a complex,
      multifactorial manner, and experimental or observational approaches must take
      this fact into consideration. Two concepts that may be helpful in this regard are
      the "muscle compartment theory," by which different muscle groups, individual
      muscles, or muscle areas may react differently to a variety of stimuli and
      pathogenic factors, and the "oil well analogy," which reflects the complexity and
      variability of the energy resource depletion mechanisms in cells and tissues,
      leading to structural remodeling and functional adaptation or impairment.

PMID- 16971350
TI  - Fetal calf serum versus human serum: ultrastructural evaluation of protein
      support influence on human ovarian tissue cryopreservation.
AB  - The aim of this study was to examine the effect of the different protein supports
      in the cryopreservation solution on improving human ovarian tissue preservation
      after frozen-thawed procedures. Biopsies of ovarian cortical tissue were obtained
      from 14 subjects. All specimens were cryopreserved using a slow freezing/rapid
      thawing method in a solution consisting of propanediol and sucrose in different
      proportions of 3 protein supports: 30% human serum (HS) (solution A), 20% HS
      (solution B), or 20% fetal calf serum (solution C). After thawing, 191 follicles
      and a total of 70 samples were analyzed using transmission electron microscopy
      (TEM). The post-thaw preservation rate of the follicles in solution A was
      significantly higher with respect to solution C (p < 0.05). Unlike the follicles,
      the stromal cell morphology was not affected by any of the solutions
      investigated. By comparing stromal morphology and the patient age, it was found
      that HS better preserved the tissue in patients over 20 years of age with respect
      to younger ones, which showed a wider variability in ovarian preservation. TEM
      evaluation showed that 30% HS is more suitable for human ovarian tissue
      cryopreservation, and research should be focused on defining cryopreservation
      protocols specific to young patients.

PMID- 16971351
TI  - Axonal degeneration with unusual lesions of the myelin in an occupational
      neuropathy.
AB  - A 35-year-old man had prolonged occupational exposure to lead carboxylate,
      triethylbenzene, xylene, and dichloromethane, when he developed a subacute
      predominantly sensory neuropathy. Ultrastructural examination of a peripheral
      nerve biopsy showed axonal degeneration and unusual lesions of the myelin, with
      Schwann cell sequestration of vesicular and lamellar debris. Biochemical analysis
      of lead in a frozen peripheral nerve specimen revealed no significant difference
      between the propositus and a control. The authors were unable to find any similar
      peripheral nerve lesions in the literature dealing with neurotoxic chemicals. Any
      of the several organic solvents could have equally caused the neuropathy and may
      have been potentialized by the other chemicals.

PMID- 16971352
TI  - PDGF and microvessel wall remodeling in adult lung: imaging PDGF-Rbeta and PDGF
      BB molecules in progenitor smooth muscle cells developing in pulmonary
      hypertension.
AB  - Smooth muscle cells are relatively rare cells in the microvessels of the normal
      adult lung but develop in high numbers in the clinical pulmonary hypertensions
      (PHs). Understanding this cellular response has profound implications for
      determining the pathogenesis of PH, and for the development of therapeutic
      strategies, yet little is known of the angiogenic molecules responsible. The
      authors have previously shown that interstitial fibroblasts, and intermediate
      cells, are the progenitors of smooth muscle cells developing in adult lung
      microvessels in an in vivo model of experimental PH. The present study evaluates
      PDGF-Rbeta/PDGF-BB, an important angiogenic signaling pathway, using antibodies
      linked to protein A-gold (pA-AU) and quantitative high-resolution imaging
      techniques to detect expression by these cells. Each progenitor cell type in the
      control lung expressed PDGF-Rbeta and PDGF-BB. In the hypertensive lung, PDGF
      Rbeta was highly expressed by fibroblasts developing as perivascular cells, the
      mean number of pA-AU labeled antigenic sites per cell profile, and their density
      (microm(-2)), increasing with time: in intermediate cells the mean number of
      sites per cell profile, although not their density (microm(-2)), also increased
      with time but less so than in the fibroblasts. In clear contrast to the RTK,
      constitutive expression levels of PDGF-BB were low in each progenitor cell type
      and remained restricted in the hypertensive lung.

PMID- 16971353
TI  - Dermatofibroma and dermatofibrosarcoma protuberans: a comparative ultrastructural
      study.
AB  - Dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) are dermal tumors
      whose histogenesis has not been well defined to date. The differential diagnosis
      in most cases is established in routine H/E sections and may be confirmed by
      immunohistochemistry, but there are atypical variants of DF with less clear
      histological differences and non-conclusive immunohistochemical results. In those
      cases, electron microscopy studies may be useful in establishing the diagnosis.
      The authors describe in detail the ultrastructural characteristics of 38 cases of
      DFSP and 10 cases of DF. The objective was to establish the ultrastructural
      features for differential diagnosis, and to identify the possible histogenesis of
      both neoplasms. DFSP is formed by stellate or spindled cells with long, slender,
      ramified cell processes joined by primitive junctions. Subplasmalemmal densities
      were frequently seen in the processes. Another common finding was the presence of
      multivesicular buds (MVB), peculiar structures that contain microvesicles
      abutting from the cell membrane. In contrast, DF is characterized by a
      proliferation of multiple capillary vessels with prominent endothelium and a
      perivascular population of ovoid or spindled cells devoid of cell processes.
      These latter cells featured intracytoplasmic lipid material (p < .001),
      infrequent subplasmalemmal densities (p < .001), and absence of MVB (p < .001).
      With the ultrastructural characteristics and the constant expression of CD34 in
      DFSP, a probable origin in dermal dendrocytes is postulated for this tumor. The
      histogenesis of DF is less clear, but an origin from FXIIIa modified perivascular
      dermal dendrocytes is proposed.

PMID- 16971354
TI  - Ultrastructure of low-grade intraosseous osteosarcoma of bone: a comparative
      study with fibrous dysplasia and parosteal osteosarcoma.
AB  - The ultrastructure of low-grade intraosseous osteosarcoma (LGOS) is not well
      documented in the literature. Four cases of LGOS are described with an emphasis
      on its distinguishing characteristics as well those it shares with other lesions.
      The predominant cells of LGOS are fibroblasts with well-developed rough
      endoplasmic reticulum and mild focal immunoreactivity to SMA and MSA. Few
      osteoblasts and myofibroblasts are present. Transition cells between fibroblasts
      and osteoblasts are also noted. The fibroblasts are closely related to
      osteoblasts from a histological and functional point of view, and phenotypically
      are probably modified osteoblasts. Comparative ultrastructural studies between
      LGOS and fibrous dysplasia (FD) reveal basic similarities, although the cells in
      LGOS are larger with more of an abundance of organelles. Therefore, accurate
      differentiation between these two lesions rests at the histological and
      radiological levels. LGOS and parosteal osteosarcomas (PO) also share similar
      ultrastructural features. In the case samples in this study, an unusual type of
      multilayered amorphous material was found in the osteoid matrix of a case of LGOS
      and one of PO. This probably emphasizes the morphologic similarities between
      these 2 tumors.

PMID- 16971355
TI  - Gastric hepatoid adenocarcinoma with autophagy-related necrosis-like tumor cell
      death: report of a case.
AB  - A case of hepatoid adenocarcinoma of the stomach is presented. The characteristic
      features of the tumor are summarized on the basis of the authors' experience and
      the literature. Ultrastructural examination revealed patchy condensations of
      chromatin throughout the nucleus suggestive of necrosis-like programmed cell
      death (PCD). These nuclear alterations were associated with the occurrence of
      vacuoles and lipofuscins, conferring an autophagic phenotype to this PCD. Thus,
      the case reported here provides an example of autophagic-related necrosis-like
      PCD. Alternative PCDs are reviewed and their morphologic distinction is
      discussed.

PMID- 16971356
TI  - Chordoid meningioma: case report and literature review.

PMID- 16971357
TI  - Plasma cell dyscrasia with kappa light-chain crystals in proximal tubular cells:
      a histological, immunofluorescent, and ultrastructural study.
AB  - This is a case report of a 56-year-old man with plasma cell dyscrasia who
      presented with proximal tubulopathy manifested as kappa light-chain crystal
      deposition in the proximal convoluted tubular cells. This was associated with
      mild cellular damage. The crystals were seen as negative images with the
      hematoxylin-eosin and periodic acid-Schiff (PAS) stains. They were identified as
      kappa light-chains by immunofluorescent imaging and confirmed by immunoelectron
      microscopy. Ultrastructurally, the crystals appear to be located within
      lysosomes. No deposits of light-chains were seen elsewhere in the kidney biopsy.

PMID- 16971358
TI  - Illustration of thin basement membrane disease.

PMID- 16971360
TI  - Tazarotene versus tazarotene plus hydroquinone in the treatment of photodamaged
      facial skin: a multicenter, double-blind, randomized study.
AB  - OBJECTIVES: To compare the efficacy and tolerability of tazarotene plus
      hydroquinone versus tazarotene alone in the treatment of facial photodamage.
      METHODS: Patients with facial mottled hyperpigmentation of at least moderate
      severity and an overall integrated assessment of photodamage score of at least
      moderate applied tazarotene 0.1% cream each evening and either hydroquinone 4%
      cream or placebo cream each morning for up to 24 weeks. RESULTS: Among 131
      patients enrolled, 114/124 (92%) with exit data completed. Both regimens were
      highly effective in reducing photodamage, with tazarotene plus hydroquinone
      showing superiority over tazarotene alone for some efficacy measures. The
      incidence of >or=1-grade improvement from baseline (on a scale of none, minimal,
      mild, moderate, or severe) was significantly greater with tazarotene plus
      hydroquinone than with tazarotene alone for lentigines (weeks 12-24, p<or=0.01)
      and mottled hyperpigmentation (week 16, p<or=0.05). The incidence of >or=50%
      global improvement was also significantly superior with the combination regimen
      as early as week 8 (p<or=0.01). Both regimens were associated with good
      tolerability and high patient satisfaction (no significant between-group
      differences). CONCLUSIONS: The adjunctive use of hydroquinone can enhance the
      efficacy of tazarotene in reducing dyspigmentation associated with photodamage.

PMID- 16971361
TI  - Use of phosphatidylcholine for the correction of lower lid bulging due to
      prominent fat pads.
AB  - BACKGROUND: Orbital fat tissue, while important in protecting the eye, can
      protrude during aging, making a patient look 'tired'. Surgical correction,
      although traditionally the treatment of choice, can lead to scarring.
      Phosphatidylcholine (PPT) has been shown to reduce the size of these fat pads
      after direct injection. The compound, licensed in Europe for intravenous
      treatment of fat embolism, has recently gained interest for reducing localized
      fat by subcutaneous injection. However, there is a dearth of clinical data
      relating to efficacy and side effects. OBJECTIVE: An open-label study was
      conducted in 21 subjects with the goal of reducing the infraorbital fat pad size.
      The objective of this study was to evaluate the efficacy and safety of PPT after
      injection into infraorbital fat pads. METHODS: Twenty-one subjects were injected
      with 0.4 ml of PPT every 6 weeks to reduce prominent infraorbital fat pads. Pre-
      and post-treatment digital photographs were taken to document efficacy. In
      addition, side effects were recorded on a follow-up questionnaire. RESULTS: In
      all, 74% of the subjects showed significant improvement after two to three
      treatments. Five of the enrolled subjects (23%) were non-responsive after two or
      more procedures and their treatment was discontinued. None of the patients had
      adverse side effects other than mild burning, erythema and swelling at the
      injection site. Nearly every patient maintained the results with no evidence of
      tissue damage after 6 months. CONCLUSION: PPT injection into infraorbital fat
      pads resulted in a satisfactory cosmetic effect in most treated subjects. Most
      subjects required more than one treatment. This simple, office-based treatment
      provides a non-surgical alternative to patients with prominent infraorbital fat
      pads. More clinical data are required to fully assess the long-term safety and
      efficacy of this procedure.

PMID- 16971362
TI  - Acne scar correction using calcium hydroxylapatite in a carrier-based gel.
AB  - OBJECTIVES: This study sought to determine the efficacy and safety profile of
      calcium hydroxylapatite filler in the treatment of acne scars. METHODS: Ten
      subjects with a variety of acne scars were treated with calcium hydroxylapatite
      filler. RESULTS: Saucerized acne scars responded to treatment; ice-pick scars did
      not. Results lasted, at least to some degree, for 12 months after treatment. No
      significant treatment complications were noted. CONCLUSIONS: Calcium
      hydroxylapatite is a safe and effective long-term filler for the treatment of
      saucerized acne scars.

PMID- 16971363
TI  - The use of a constant spectrum, uniform temporal profile intense pulsed light
      source for long-term hair removal in Asian skin.
AB  - Phototherapy has become a treatment of choice in many areas of medicine. Light
      can deliver energy to tissue selectively, targeting specific structures in order
      to induce the desired therapeutic outcome. For the safe and effective removal of
      unwanted hair, the key optical parameters are wavelength, pulse duration and
      energy density, and can vary dependent upon skin and hair color. In recent years,
      the use of broad spectrum white light sources has proved to be safe and
      efficacious in the removal of hair with minimal short- or long-term side effects.
      Whilst these highly flexible devices can achieve the desired results, there is
      scope for improvement. There are two key limitations to these devices: an
      inability to produce a 'true' long pulse matched to the thermal relaxation time
      of the hair structure and fluctuations in the output spectrum can lead to
      ineffective treatment with an increased risk of side effects. This paper
      describes an alternative approach to producing long pulse, constant spectrum
      optical pulses and presents clinical data showing improved efficacy in long-term
      hair removal.

PMID- 16971364
TI  - Past, present, and future: vascular lasers/light devices.
AB  - Vascular lasers were among the first available cutaneous light-based
      technologies. The past 20 years has seen a variety of safe and effective laser
      and light-based vascular treatment devices. This article provides a review of the
      medical and scientific literature, which concludes that newer lasers have led to
      increasing success and safety in the treatment of cutaneous vascular lesions.

PMID- 16971365
TI  - Effect of temperature-controlled cooling on light-based skin treatments.
AB  - BACKGROUND: A variety of cooling devices are used to provide safe and effective
      light based treatments of the skin. Despite the documented safety of such cooling
      devices, there is scant data on the epidermal effects of different cooling
      temperatures when used with such technologies. OBJECTIVE: Determine the impact of
      changes in cooling temperatures on epidermal changes during broad based light
      source treatment. METHODS: A human arm was treated with a 515 nm filtered broad
      based lights source using varying contact cooling temperatures. RESULTS:
      Extensive epidermal crusting versus minimal epidermal crusting was noted with
      only an 8 degrees centigrade temperature change in contact cooling. CONCLUSION:
      Not only does epidermal cooling lead to safer light based procedures, but small
      temperature changes in cooling can lead to the difference between minimal versus
      extensive epidermal changes.

PMID- 16971366
TI  - Avascular osteonecrosis after hyperthermia in children and adolescents with
      pelvic malignancies: a retrospective analysis of potential risk factors.
AB  - PURPOSE: In children with locally advanced or recurrent malignant tumours,
      prognosis can be improved by regional deep hyperthermia (RHT) in combination with
      platin-based chemotherapy. However, because of the increasing number of patients
      that achieve long-time remission with this therapy, it is necessary to evaluate
      long-term sequelae of thermochemotherapy. During the years 1993-2004 one has
      observed avascular osteonecrosis (AON) of the femoral head after RHT in seven
      children with pelvic germ cell tumours or rhabdomyosarcomas. METHODS: Although
      AON may develop in patients with malignancies treated with chemo- or radiotherapy
      alone, RHT might nevertheless contribute to the occurrence of AON. In order to
      determine potential risk factors for AON after RHT, this study analysed the
      relationship of AON to the patient's age, medical history and treatment
      parameters such as thermal dose equivalent and power output. RESULTS AND
      CONCLUSIONS: In the present study AON was associated with young age as well as
      intensity of hyperthermia indicated by high power levels that exceed 20 W per kg
      body weight and/or application of eight or more heat sessions as well as
      additional radiotherapy. Based on this observation, it was assumed that an
      optimized three dimensional thermal field modelling may be helpful to avoid
      hazardous temperatures in the femoral heads during RHT treatment and to reduce
      AON of the femoral heads.

PMID- 16971367
TI  - Intra-luminal thermometry: is tissue type assignment a necessity for thermal
      analysis?
AB  - INTRODUCTION: Tissue type assignment, i.e. differentiation tumour from normal
      tissue, is a normal procedure for interstitial thermometry. In our department,
      thermometry in patients with a tumour in the lower pelvis is usually restricted
      to the intra-luminal tracks. It is unknown whether discrimination between normal
      and tumour tissue is relevant for deep regional hyperthermia thermal dosimetry
      using only intra-luminal tumour contact and tumour adjacent thermometry. This
      study has analysed the acquired temperature data in order to answer this
      question. PATIENTS AND METHODS: Seventy-five patients with locally advanced
      cervical carcinoma were selected randomly. Patients were treated with a two or
      three modality combination, i.e. radiotherapy +hyperthermia or radiotherapy +
      hyperthermia + chemotherapy from October 1997 to September 2003. The first 100
      hyperthermia treatments fulfilling the only selection criterion: no displacement
      of the thermometry catheter along the insertion length during the treatment, were
      included in the study, resulting in 43 patients with one-to-five
      treatments/patient (median 2). Using RHyThM (Rotterdam Hyperthermia Thermal
      Modulator), for each single treatment tissue type, was defined on the basis of
      information given by a CT scan in radiotherapy position. A step change in the
      slope of the profile of the first temperature map was identified to verify the
      insertion length of the catheter. RESULTS: The average T50 (median temperature)
      in bladder tumour indicative, vagina tumour contact and rectum tumour indicative
      was 40.9 +/- 0.9 degrees C, 39.7 +/- 0.9 degrees C and 40.6 +/- 0.8 degrees C,
      respectively. The average normal tissue T50 in bladder, vagina and rectum was
      40.8 +/- 0.9 degrees C, 40.1 +/- 0.9 degrees C and 40.7 +/- 0.8 degrees C,
      respectively. The differences between bladder tumour indicative T50 and bladder
      normal tissue T50 and also between vagina tumour contact T50 and vagina normal
      tissue T50 were significant ( p = 0.0001). No statistical difference was found
      between rectum tumour indicative t50 and rectum normal tissue T50. CONCLUSION: At
      present the cause of the temperature difference is not known. However, as the
      difference between tumour (indicative/contact) and normal tissue is very small
      and considering also the inaccuracy in the tissue type assignment it can be
      stated that this study does not provide sufficient evidence to conclude that the
      statistical difference has clinical relevance. Therefore, it was concluded that
      at this time there is no need to differentiate between normal and tumour tissue
      in intra-luminal thermometry.

PMID- 16971368
TI  - Evaluation of a dual-arm Archimedean spiral array for microwave hyperthermia.
AB  - PURPOSE: This effort describes a third-party performance evaluation of a novel,
      commercial, dual-armed Archimedean spiral array hyperthermia applicator. The
      applicator is analysed for its ability to couple efficiently into muscle
      equivalent phantom loads, operate over a broad bandwidth to help accommodate
      variable tissue properties and generate predictable and repeatable SAR contours
      that are adaptable to clinically probable disease shapes. MATERIALS AND METHODS:
      Characterization of the applicator includes E-field and return-loss measurements
      in liquid muscle tissue-equivalent phantom, as well as comparison of 'treatment
      planning' simulations of several possible array SAR patterns with measured SAR
      from non-coherently driven spiral array antennae. RESULTS: The applicator
      demonstrates a reasonably low return loss over a large bandwidth and the ability
      to generate a very uniform heating pattern. Ability to adjust SAR contours
      spatially to fit specific shapes is also demonstrated. CONCLUSIONS: This device
      should prove a welcome addition to a currently limited set of superficial heating
      applicators to provide controllable heating of superficial tissue disease.

PMID- 16971369
TI  - Thermal characteristics of microwave ablation in the vicinity of an arterial
      bifurcation.
AB  - PURPOSE: The objective of this research was to reveal the thermal characteristics
      of microwave ablations in the vicinity of an arterial bifurcation. METHODS: The
      temperature distribution after microwave heating of a liver-like material in the
      close proximity of an arterial bifurcation was simulated using the finite element
      method. Coupled fluid flow and solid heat transfer were taken into consideration
      and a three-dimensional analysis was performed. An experimentally determined SAR
      (specific absorption rate) generated by the absorption of microwaves in liver
      like material was used in the analysis instead of utilizing electromagnetic
      calculations. Several different tests of time-controlled ablations with varying
      distances between the microwave antenna and the bifurcation were performed and
      detailed temperature distributions near the bifurcation were obtained. RESULTS:
      The interaction between the recirculation flow in the bifurcation and the heat
      transfer in the surrounding tissue makes the temperature distribution near the
      bifurcation complicated. Most importantly, after a period of continuous heating
      with constant microwave output power, the maximum temperatures caused by the
      ablation did not always increase with the distance between the antenna and the
      bifurcation. CONCLUSION: It can be concluded that inadequate ablations can be the
      result not only from a close proximity between the antenna and the blood vessel,
      but also from a complicated blood flow in large vessels whose structure causes
      recirculation flow.

PMID- 16971370
TI  - HSP27 phosphorylation increases after 45 degrees C or 41 degrees C heat shocks
      but not after non-thermal TDMA or GSM exposures.
AB  - PURPOSE: Experiments with cultured HeLa, S3 and E.A. Hy296 cells were performed
      to determine if exposure to acute (30 min at 45 degrees C) or chronic (2 h at 41
      degrees C) heat shocks or to non-thermal exposures of radiofrequency radiation
      (RF) induce changes in HSP27 phosphorylation. MATERIALS AND METHODS: The
      radiofrequency (RF) exposures used in this study were 847 MHz time division
      multiple access modulated (TDMA) at a specific absorption rate (SAR) of 5 W kg-1
      for 1, 2 or 24 h or 900 MHz GSM modulated (GSM) at a SAR of 3.7 W kg-1 for 1, 2
      or 5 h. HSP27 phosphorylation was evaluated by resolving the various
      phosphorylation forms using two-dimensional gel electrophoresis measuring the
      relative amount of each by densitometry. Alternatively, an antibody specific for
      phosphorylated HSP27 was used to detect changes in HSP27 phosphorylation levels.
      All heat shock and RF exposure conditions were analysed simultaneously along with
      a matched incubator control sample. Each experiment was repeated three times.
      RESULTS: Following heat shock, the degree of phosphorylation of HSP27 varied with
      the heat dose, with acute hyperthermia (45 degrees C) having an increased
      proportion of higher phosphorylated forms. Exposure of HeLa S3 cells to 5 W kg-1
      TDMA for 1, 2 or 24 h did not induce significant differences in the levels of
      HSP27 phosphorylation compared to incubator control or sham. Exposure of E.A.
      Hy926 cells to 3.7 W kg-1 900 MHz GSM for 1, 2 or 5 h did not induce significant
      differences in the levels of HSP27 phosphorylation compared to sham exposed.
      CONCLUSIONS: Acute and moderate hyperthermia significantly increase HSP27
      phosphorylation, but there was no significant change in the levels of HSP27
      following non-thermal exposure to TDMA and GSM modulated RF radiations.

PMID- 16971373
TI  - Impact of androgen-induced oxidative stress on hypertension in male SHR.
AB  - Men have higher blood pressure than women, and androgens and oxidative stress
      have been implicated as playing roles in this sexual dimorphism. The
      spontaneously hypertensive rat (SHR) is an animal model of both androgen- and
      oxidative stress-mediated hypertension. Therefore, the present studies were
      performed to test the hypothesis that androgens cause hypertension in SHR in part
      by stimulating superoxide production via NADPH oxidase. Castration of male SHR
      reduced blood pressure by 15% and attenuated both basal and NADPH-stimulated
      superoxide production in kidney cortical homogenates. Expression of p47(phox) and
      gp91(phox) but not p22(phox) subunits of NADPH oxidase were significantly lower
      in kidney cortex from castrated males compared with intact males. Moreover,
      inhibition of NADPH oxidase with apocynin caused approximately 15 mmHg reduction
      in blood pressure and reduced basal and NADPH-stimulated superoxide production in
      intact male SHR, but had no effect on blood pressure or superoxide production in
      castrated males. These data support the hypothesis that androgens cause oxidative
      stress and thereby increase blood pressure in male SHR via an NADPH oxidase
      dependent mechanism.

PMID- 16971374
TI  - Hypertension and impaired vascular function in a female mouse model of systemic
      lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease
      that predominantly affects women during their reproductive years. Although women
      with SLE have hypertension, the underlying mechanisms for this have not been
      examined. Despite the fact that inflammation is associated with altered
      endothelial and vascular function, the role of altered vascular function in the
      development of hypertension during SLE is unclear. In the present study, we
      tested whether a mouse model of SLE (NZBWF1) develops hypertension and examined
      whether increased blood pressure was associated with impaired endothelial
      dependent relaxation. Female NZBWF1 mice were studied at 8, 20, and 36 wk of age.
      By 36 wk, urinary albumin and antinuclear antibodies were increased in SLE
      compared with control mice. Mean arterial pressure, measured by radiotelemetry,
      was significantly increased in SLE mice (124 +/- 4 mmHg, n = 10) compared with
      control NZW/LacJ mice (111 +/- 3 mmHg, n = 7) at 36 wk. Isolated carotid arteries
      from NZBWF1 mice, precontracted with U-46619 for assessment of endothelial
      dependent relaxation, demonstrated a progressively impaired relaxation to ACh
      with age, although endothelial nitric oxide synthase mRNA expression was not
      different. Maximal tension generated by 5-hydroxytryptamine was increased in
      carotid arteries from NZBWF1 mice compared with controls at 8, 20, and 36 wk of
      age, suggesting a role for altered vascular function early on in the progression
      of SLE. Taken together, our data support a role for altered endothelial function
      as a contributing factor to the development of hypertension during SLE.

PMID- 16971375
TI  - Modular regulation analysis of heart contraction: application to in situ
      demonstration of a direct mitochondrial activation by calcium in beating heart.
AB  - Heart contraction is characterized by the absence of changes in energetic
      intermediates in response to a large increase of activity. Until now no
      experimental approach could address this question concerning the intact beating
      heart. Ca(2+) plays a crucial role in the excitation-contraction coupling, and in
      vitro studies have evidenced that Ca(2+) may also directly activate mitochondrial
      oxidative phosphorylation. We applied our new in situ modular control and
      regulation analysis on isolated beating rat heart perfused under two different
      calcium concentrations with pyruvate or glucose as the substrate. Modular control
      analysis demonstrated experimentally that, although control by energy production
      was slightly higher under glucose conditions compared with pyruvate, most of the
      control of heart contraction resides in energy utilization. This behavior is the
      direct consequence of the high sensitivity (elasticity) of the energy producer
      processes to ATP utilization. Interestingly, the increase in heart metabolic rate
      by Ca(2+) did not significantly change the pattern of control distribution. The
      regulation analysis performed under the two calcium conditions demonstrated a
      balanced activation of myofibrils ATPases, and mitochondrial ATP synthesis in
      response to Ca(2+) increase. This first study demonstrates in situ the hypothesis
      that the energetic adequation in heart contraction is mediated by a parallel
      activation of both processes of energy production and utilization by Ca(2+). The
      results presented here show that modular control and regulation analyses allow in
      situ study of internal regulations in intact beating heart energetics and
      function and may now be applied to heart dysfunctions and therapeutic effects.

PMID- 16971376
TI  - Multiple comparisons distortions of parameter estimates.
AB  - In experiments involving many variables, investigators typically use multiple
      comparisons procedures to determine differences that are unlikely to be the
      result of chance. However, investigators rarely consider how the magnitude of the
      greatest observed effect sizes may have been subject to bias resulting from
      multiple testing. These questions of bias become important to the extent
      investigators focus on the magnitude of the observed effects. As an example, such
      bias can lead to problems in attempting to validate results, if a biased effect
      size is used to power a follow-up study. An associated important consequence is
      that confidence intervals constructed using standard distributions may be badly
      biased. A bootstrap approach is used to estimate and adjust for the bias in the
      effect sizes of those variables showing strongest differences. This bias is not
      always present; some principles showing what factors may lead to greater bias are
      given and a proof of the convergence of the bootstrap distribution is provided.

PMID- 16971377
TI  - Numerical equivalence of imputing scores and weighted estimators in regression
      analysis with missing covariates.
AB  - Imputation, weighting, direct likelihood, and direct Bayesian inference (Rubin,
      1976) are important approaches for missing data regression. Many useful
      semiparametric estimators have been developed for regression analysis of data
      with missing covariates or outcomes. It has been established that some
      semiparametric estimators are asymptotically equivalent, but it has not been
      shown that many are numerically the same. We applied some existing methods to a
      bladder cancer case-control study and noted that they were the same numerically
      when the observed covariates and outcomes are categorical. To understand the
      analytical background of this finding, we further show that when observed
      covariates and outcomes are categorical, some estimators are not only
      asymptotically equivalent but also actually numerically identical. That is,
      although their estimating equations are different, they lead numerically to
      exactly the same root. This includes a simple weighted estimator, an augmented
      weighted estimator, and a mean-score estimator. The numerical equivalence may
      elucidate the relationship between imputing scores and weighted estimation
      procedures.

PMID- 16971378
TI  - Constitutive and vitamin C-induced, NO-catalyzed release of heparan sulfate from
      recycling glypican-1 in late endosomes.
AB  - The recycling heparan sulfate (HS)-containing proteoglycan glypican-1 (Gpc-1) is
      processed by nitric oxide (NO)-catalyzed deaminative cleavage of its HS chains at
      N-unsubstituted glucosamines. This generates anhydromannose (anMan)-containing HS
      degradation products that can be detected by a specific antibody. Here we have
      attempted to identify the intracellular compartments where these products are
      formed. The anMan-positive degradation products generated constitutively in human
      bladder carcinoma cell line (T24) or fibroblasts appeared neither in caveolin-1
      associated vesicles nor in lysosomes. In Niemann-Pick C-1 (NPC-1) fibroblasts,
      where deaminative degradation is abrogated, formation of anMan-positive products
      can be restored by ascorbate. These products colocalized with Rab7, a marker for
      late endosomes. When NO-catalyzed degradation of HS was depressed in mouse
      neuroblastoma cell line (N2a) by using 3-beta[2(diethylamino) ethoxy]androst-5-en
      17-one (U18666A), both ascorbate and dehydroascorbic acid restored formation of
      anMan-positive products that colocalized with Rab7. In T24 cells, constitutively
      generated anMan-positive products colocalized with both Rab7 and Rab9, whereas
      Gpc-1 colocalized with Rab9, a marker for transporting endosomes. Inhibition of
      endosomal acidification, which blocks transfer from early (Rab5) to late (Rab7)
      endosomes, abrogated deaminative degradation of HS. This could also be overcome
      by the addition of ascorbate, which induced formation of anMan-positive
      degradation products that colocalized with Rab7. After (35)S-sulfate labeling,
      similar degradation products were recovered in Rab7-positive vesicles. We
      conclude that NO-catalyzed degradation of HS may begin in early endosomes but is
      mainly taking place in late endosomes.

PMID- 16971379
TI  - Arraying glycomics: a novel bi-functional spacer for one-step microscale
      derivatization of free reducing glycans.
AB  - Glycan array development is limited by the complexity of efficiently generating
      derivatives of free reducing glycans with primary amines or other functional
      groups. A novel bi-functional spacer with selective reactivity toward the free
      glycan and a second functionality, a primary amine, was synthesized. We
      demonstrated an efficient one-step derivatization of various glycans including
      naturally isolated N-glycans, O-glycans, milk oligosaccharides, and bacterial
      polysaccharides in microgram scale. No protecting group manipulations or
      activation of the anomeric center was required. To demonstrate its utility for
      glycan microarray fabrication, we compared glycans with different amine-spacers
      for incorporation onto an amine-reactive glass surface. Our study results
      revealed that glycans conjugated with this bi-functional linker were effectively
      printed and detected with various lectins and antibodies.

PMID- 16971380
TI  - Structural characterization of N-glycans from the freshwater snail Biomphalaria
      glabrata cross-reacting with Schistosoma mansoni glycoconjugates.
AB  - The human parasitic trematode Schistosoma mansoni has a complex life cycle that
      includes the freshwater snail Biomphalaria glabrata as intermediate host. Within
      each stage, the parasite synthesizes a wide array of glycoconjugates, exhibiting,
      in part, unique carbohydrate structures. In addition, the parasite expresses
      definitive host-like sugar epitopes, such as Lewis X determinants, supporting the
      concept of carbohydrate-mediated molecular mimicry as an invasion and survival
      strategy. In the present study, we investigated whether common carbohydrate
      determinants occur also at the level of the intermediate host. To this end, a
      structural characterization of hemolymph glycoprotein-N-glycans of B. glabrata
      was performed. N-glycans were released from tryptic glycopeptides and labeled
      with 2-aminopyridine. Sugar chains serologically cross-reacting with S. mansoni
      glycoconjugates were isolated by immunoaffinity chromatography using a polyclonal
      antiserum directed against schistosomal egg antigens and fractionated by Aleuria
      aurantia lectin affinity chromatography and high-performance liquid
      chromatography. Obtained glycans were analyzed by different mass spectrometric
      techniques as well as by monosaccharide constituent and linkage analysis. The
      results revealed a highly heterogeneous oligosaccharide pattern. Cross-reacting
      species represented about 5% of the total glycans and exhibited a terminal
      Fuc(alpha1-3)GalNAc unit, a (1-2)-linked xylosyl residue, or both types of
      structural motifs. In conclusion, our study demonstrates the presence of common
      carbohydrate epitopes also at the level of S. mansoni and its intermediate host.

PMID- 16971381
TI  - Dependence of neurotrophic factor activation of Trk tyrosine kinase receptors on
      cellular sialidase.
AB  - A direct link between receptor glycosylation and activation following natural
      ligand interaction has not been observed. Here, we discover a membrane sialidase
      controlling mechanism that depends on ligand binding to its receptor to induce
      enzyme activity which targets and desialylates the receptor and, consequently,
      causes the induction of receptor dimerization and activation. We also identify a
      specific sialyl alpha-2,3-linked beta-galactosyl sugar residue of TrkA tyrosine
      kinase receptor, which is rapidly targeted and hydrolyzed by the sialidase. Trk
      expressing cells and primary cortical neurons following stimulation with specific
      neurotrophic growth factors express a vigorous membrane sialidase activity.
      Neuraminidase inhibitors, Tamiflu, BCX1812, and BCX1827, block sialidase activity
      induced by nerve growth factor (NGF) in TrkA-PC12 cells and by brain-derived
      neurotrophic factor (BDNF) in primary cortical neurons. In contrast, the
      neuraminidase inhibitor, 2-deoxy-2,3-dehydro-N-acetylneuraminic acid, specific
      for plasma membrane ganglioside Neu3 and Neu2 sialidases has no inhibitory effect
      on NGF-induced pTrkA. The GM1 ganglioside specific cholera toxin subunit B
      applied to TrkA-PC12 cells has no inhibitory effect on NGF-induced sialidase
      activity. Neurite outgrowths induced by NGF-treated TrkA-PC12 and BDNF-treated
      PC12(nnr5) stably transfected with TrkB receptors (TrkB-nnr5) cells are
      significantly inhibited by Tamiflu. Our results establish a novel mode of
      regulation of receptor activation by its natural ligand and define a new function
      for cellular sialidases.

PMID- 16971382
TI  - Follicular vascularity is not predictive of pregnancy outcome in mild controlled
      ovarian stimulation and IUI cycles.
AB  - BACKGROUND: Although follicular vascularity has been shown to be a good indicator
      of oocyte quality in IVF, scant evidence is currently available on the predictive
      value of this variable in terms of pregnancy rate during controlled ovarian
      stimulation (COS) and intrauterine insemination (IUI) cycles. METHODS: Three
      hundred and eighteen patients who had received mild COS underwent transvaginal
      ultrasound scan before performing the IUI. Using power Doppler imaging,
      vascularity of follicles with a mean diameter > or =16 mm was graded into a three
      grades according to the circumference of the follicle in which flow was
      identified. When more than one follicle was observed, grading was performed for
      all of them, and the highest vascularity grade was recorded. RESULTS: Clinical
      pregnancy rate (number/total) in the low-, medium- and high-grade vascularity
      groups was 14.1% (14/99), 10.0% (10/100) and 11.8% (14/119), respectively (P =
      0.66). Similar results were observed when only monofollicular cycles were
      considered. CONCLUSIONS: Follicular vascularity does not predict the chance of
      pregnancy in women undergoing mild COS and IUI cycles.

PMID- 16971383
TI  - First recorded pregnancy and normal birth after ICSI using electrophoretically
      isolated spermatozoa.
AB  - BACKGROUND: DNA damage in the male germ line is associated with poor
      fertilization and cleavage rates, impaired embryo quality and early pregnancy
      loss. Given these associations, embryologists are keen to develop techniques that
      will allow the selection of viable spermatozoa exhibiting low levels of DNA
      damage for assisted conception purposes. METHODS: In this article, we describe a
      novel electrophoretic approach for the rapid isolation of cells possessing little
      DNA damage. The limits of the method were examined using cryostored and snap
      frozen semen samples as well as testicular biopsy material. In addition, clinical
      utility was demonstrated in a case study involving treatment of a patient
      exhibiting persistently high levels of DNA damage in his spermatozoa. RESULTS:
      From a range of difficult starting materials (biopsies, cryostored semen and snap
      frozen sperm suspensions), the electrophoretic system rapidly isolated
      populations of motile, viable, morphologically normal spermatozoa exhibiting high
      levels of DNA integrity. Clinical application in a couple suffering from long
      term infertility associated with extensive DNA damage in the male germ line led
      to the first human pregnancy following such electrophoretic sperm isolation.
      CONCLUSIONS: The electrophoretic procedure holds promise as a convenient method
      for the rapid preparation of high-quality spermatozoa for assisted conception
      purposes.

PMID- 16971385
TI  - Reconstructing the regulatory kinase pathways of myogenesis from phosphopeptide
      data.
AB  - Multiple kinase activities are required for skeletal muscle differentiation.
      However, the mechanisms by which these kinase pathways converge to coordinate the
      myogenic process are unknown. Using multiple phosphoprotein and phosphopeptide
      enrichment techniques we obtained phosphopeptides from growing and
      differentiating C2C12 muscle cells and determined specific peptide sequences
      using LC-MS/MS. To place these phosphopeptides into a rational context, a
      bioinformatics approach was used. Phosphorylation sites were matched to known
      site-specific and to site non-specific kinase-substrate interactions, and then
      other substrates and upstream regulators of the implicated kinases were
      incorporated into a model network of protein-protein interactions. The model
      network implicated several kinases of known relevance to myogenesis including
      AKT, GSK3, CDK5, p38, DYRK, and MAPKAPK2 kinases. This combination of proteomics
      and bioinformatics technologies should offer great utility as the volume of
      protein-protein and kinase-substrate information continues to increase.

PMID- 16971384
TI  - Using phage display to select antibodies recognizing post-translational
      modifications independently of sequence context.
AB  - Many cellular activities are controlled by post-translational modifications, the
      study of which is hampered by the lack of specific reagents due in large part to
      their ubiquitous and non-immunogenic nature. Although antibodies against
      specifically modified sequences are relatively easy to obtain, it is extremely
      difficult to derive reagents recognizing post-translational modifications
      independently of the sequence context surrounding the modification. In this
      study, we examined the possibility of selecting such antibodies from large phage
      antibody libraries using sulfotyrosine as a test case. Sulfotyrosine is a post
      translational modification important in many extracellular protein-protein
      interactions, including human immunodeficiency virus infection. After screening
      almost 8000 selected clones, we were able to isolate a single specific single
      chain Fv using two different selection strategies, one of which included elution
      with tyrosine sulfate. This antibody was able to recognize sulfotyrosine
      independently of its sequence context in test peptides and a number of different
      natural proteins. Antibody reactivity was lost by antigen treatment with
      sulfatase or preincubation with soluble tyrosine sulfate, indicating its
      specificity. The isolation of this antibody signals the potential of phage
      antibody libraries in the derivation of reagents specific for post-translational
      modifications, although the extensive screening required indicates that such
      antibodies are extremely rare.

PMID- 16971386
TI  - Transcriptional regulatory cascade for elastase production in Vibrio vulnificus:
      LuxO activates luxT expression and LuxT represses smcR expression.
AB  - Vibrio vulnificus causes diseases through actions of various virulence factors,
      including the elastase encoded by the vvpE gene. Through transposon mutagenesis
      of V. vulnificus, vvpE expression was shown to be increased by luxO mutation.
      Since the vvpE gene is known to be positively regulated by SmcR via direct
      binding to the vvpE promoter, the role of LuxO in smcR expression was
      investigated. The luxAB-transcriptional fusions containing different lengths of
      the smcR promoter region indicated that the smcR transcription was negatively
      regulated by LuxO and that a specific upstream region of the smcR gene was
      required for this repression. Since LuxO is a known member of positive
      regulators, the negative regulation of smcR transcription by LuxO prompted us to
      identify the factor(s) linking LuxO and smcR transcription. LuxT was isolated in
      a ligand fishing experiment using the smcR upstream region as bait, and smcR
      expression was increased by luxT mutation. Recombinant LuxT bound to a specific
      upstream region of the smcR gene, -154 to -129 relative to the smcR transcription
      start site. The expression of luxT was positively regulated by LuxO, and the luxT
      promoter region contained a putative LuxO-binding site. Mutagenesis of the LuxO
      binding site in the luxT promoter region resulted in a loss of transcriptional
      control by LuxO. Therefore, this study demonstrates a transcriptional regulatory
      cascade for elastase production, where LuxO activates luxT transcription and LuxT
      represses smcR transcription.

PMID- 16971387
TI  - Dimerization of Laforin is required for its optimal phosphatase activity,
      regulation of GSK3beta phosphorylation, and Wnt signaling.
AB  - Epilepsy of progressive myoclonus type 2 gene A (EPM2A) encodes a dual
      specificity protein phosphatase called Laforin. Laforin is also a tumor
      suppressor that dephosphorylates GSK3beta at the critical Ser9 position and
      regulates Wnt signaling. The epilepsy-causing mutations have a deleterious effect
      on phosphatase activity, regardless of whether they locate in the carbohydrate
      binding domain (CBD) at the N terminus or the dual specificity phosphatase domain
      (DSPD) at the C terminus. How mutations outside the DSPD reduce the phosphatase
      activity of Laforin remains unexplained. Here we report that Laforin expressed in
      mammalian cells forms dimers that are highly resistant to SDS treatment. Deleting
      CBD completely abolished the dimerization and phosphatase activity of Laforin.
      Moreover, all of the naturally occurring Laforin mutations tested impaired
      laforin GSK3beta dephosphorylation at Ser9 dimerization, and beta-catenin
      accumulation in nucleus. Our results demonstrate a critical role of dimerization
      in Laforin function and suggest an important new dimension in protein phosphatase
      function and in molecular pathogenesis of Lafora's disease.

PMID- 16971388
TI  - Mutational analysis of Encephalitozoon cuniculi mRNA cap (guanine-N7)
      methyltransferase, structure of the enzyme bound to sinefungin, and evidence that
      cap methyltransferase is the target of sinefungin's antifungal activity.
AB  - Cap (guanine-N7) methylation is an essential step in eukaryal mRNA synthesis and
      a potential target for antiviral, antifungal, and antiprotozoal drug discovery.
      Previous mutational and structural analyses of Encephalitozoon cuniculi Ecm1, a
      prototypal cellular cap methyltransferase, identified amino acids required for
      cap methylation in vivo, but also underscored the nonessentiality of many side
      chains that contact the cap and AdoMet substrates. Here we tested new mutations
      in residues that comprise the guanine-binding pocket, alone and in combination.
      The outcomes indicate that the shape of the guanine binding pocket is more
      crucial than particular base edge interactions, and they highlight the
      contributions of the aliphatic carbons of Phe-141 and Tyr-145 that engage in
      multiple van der Waals contacts with guanosine and S-adenosylmethionine (AdoMet),
      respectively. We purified 45 Ecm1 mutant proteins and assayed them for
      methylation of GpppA in vitro. Of the 21 mutations that resulted in unconditional
      lethality in vivo,14 reduced activity in vitro to < or = 2% of the wild-type
      level and 5 reduced methyltransferase activity to between 4 and 9% of wild-type
      Ecm1. The natural product antibiotic sinefungin is an AdoMet analog that inhibits
      Ecm1 with modest potency. The crystal structure of an Ecm1-sinefungin binary
      complex reveals sinefungin-specific polar contacts with main-chain and side-chain
      atoms that can explain the 3-fold higher affinity of Ecm1 for sinefungin versus
      AdoMet or S-adenosylhomocysteine (AdoHcy). In contrast, sinefungin is an
      extremely potent inhibitor of the yeast cap methyltransferase Abd1, to which
      sinefungin binds 900-fold more avidly than AdoHcy or AdoMet. We find that the
      sensitivity of Saccharomyces cerevisiae to growth inhibition by sinefungin is
      diminished when Abd1 is overexpressed. These results highlight cap methylation as
      a principal target of the antifungal activity of sinefungin.

PMID- 16971389
TI  - Mitochondrial metabolism in developing embryos of Brassica napus.
AB  - The metabolism of developing plant seeds is directed toward transforming primary
      assimilatory products (sugars and amino acids) into seed storage compounds. To
      understand the role of mitochondria in this metabolism, metabolic fluxes were
      determined in developing embryos of Brassica napus. After labeling with [1,2
      (13)C2]glucose + [U-(13)C6]glucose, [U-(13)C3]alanine, [U-(13)C5]glutamine,
      [(15)N]alanine, (amino)-[(15)N]glutamine, or (amide)-[(15)N]glutamine, the
      resulting labeling patterns in protein amino acids and in fatty acids were
      analyzed by gas chromatography-mass spectrometry. Fluxes through mitochondrial
      metabolism were quantified using a steady state flux model. Labeling information
      from experiments using different labeled substrates was essential for model
      validation and reliable flux estimation. The resulting flux map shows that
      mitochondrial metabolism in these developing seeds is very different from that in
      either heterotrophic or autotrophic plant tissues or in most other organisms: (i)
      flux around the tricarboxylic acid cycle is absent and the small fluxes through
      oxidative reactions in the mitochondrion can generate (via oxidative
      phosphorylation) at most 22% of the ATP needed for biosynthesis; (ii) isocitrate
      dehydrogenase is reversible in vivo; (iii) about 40% of mitochondrial pyruvate is
      produced by malic enzyme rather than being imported from the cytosol; (iv)
      mitochondrial flux is largely devoted to providing precursors for cytosolic fatty
      acid elongation; and (v) the uptake of amino acids rather than anaplerosis via
      PEP carboxylase determines carbon flow into storage proteins.

PMID- 16971390
TI  - Aberrant hepatic expression of PPARgamma2 stimulates hepatic lipogenesis in a
      mouse model of obesity, insulin resistance, dyslipidemia, and hepatic steatosis.
AB  - Insulin-resistant apoB/BATless mice have hypertriglyceridemia because of
      increased assembly and secretion of very low density apolipoprotein B (apoB) and
      triglycerides compared with mice expressing only apoB (Siri, P., Candela, N., Ko,
      C., Zhang, Y., Eusufzai, S., Ginsberg, H. N., and Huang, L. S. (2001) J. Biol.
      Chem. 276, 46064-46072). Despite increased very low density lipoprotein
      secretion, apoB/BATless mice have fatty livers. We found that hepatic mRNA levels
      of key lipogenic enzymes, acetyl-CoA carboxylase, fatty-acid synthase, and
      stearoyl-CoA desaturase-1 were increased in apoB/BATless mice compared with
      levels in apoB mice, suggesting increased lipogenesis in apoB/BATless mice. This
      was confirmed by determining incorporation of tritiated water into fatty acids.
      Neither the hepatic mRNA of the lipogenic transcription factor, SREBP-1c (sterol
      response element-binding protein 1c), nor the nuclear levels of the mature form
      of SREBP-1 protein were elevated in apoB/BATless mice. By contrast, hepatic
      levels of peroxisomal proliferator-activated receptor 2 (PPARgamma2) mRNA and
      protein were specifically increased in apoB/BATless mice, as were hepatic mRNA
      levels of two targets of PPARgamma, CD36 and aP2. Treatment of apoB/BATless mice
      for 4 weeks with intraperitoneal injections of a PPARgamma antisense
      oligonucleotide resulted in dramatic reductions of both PPARgamma1 and PPARgamma2
      mRNA, PPARgamma2 protein, and mRNA levels of fatty-acid synthase and acetyl-CoA
      carboxylase. These changes were associated with decreased hepatic de novo
      lipogenesis and hepatic triglyceride concentrations. We conclude that hepatic
      steatosis in apoB/BATless mice is associated with elevated rates of hepatic
      lipogenesis that are linked directly to increased hepatic expression of
      PPARgamma2. The mechanism whereby hepatic Ppargamma2 gene expression is increased
      and how PPARgamma2 stimulates lipogenesis is under investigation.

PMID- 16971391
TI  - The SHB adapter protein is required for normal maturation of mesoderm during in
      vitro differentiation of embryonic stem cells.
AB  - Definitive mesoderm arises from a bipotent mesendodermal population, and to study
      processes controlling its development at this stage, embryonic stem (ES) cells
      can be employed. SHB (Src homology 2 protein in beta-cells) is an adapter protein
      previously found to be involved in ES cell differentiation to mesoderm. To
      further study the role of SHB in this context, we have established ES cell lines
      deficient for one (SHB+/-) or both SHB alleles (SHB-/-). Differentiating embryoid
      bodies (EBs) derived from these ES cell lines were used for gene expression
      analysis. Alternatively, EBs were stained for the blood vessel marker CD31. For
      hematopoietic differentiation, EBs were differentiated in methylcellulose. SHB-/-
      EBs exhibited delayed down-regulation of the early mesodermal marker Brachyury.
      Later mesodermal markers relatively specific for the hematopoietic, vascular, and
      cardiac lineages were expressed at lower levels on day 6 or 8 of differentiation
      in EBs lacking SHB. The expression of vascular endothelial growth factor receptor
      2 and fibroblast growth factor receptor-1 was also reduced in SHB-/- EBs. SHB-/-
      EBs demonstrated impaired blood vessel formation after vascular endothelial
      growth factor stimulation. In addition, the SHB-/- ES cells formed fewer blood
      cell colonies than SHB+/+ ES cells. It is concluded that SHB is required for
      appropriate hematopoietic and vascular differentiation and that delayed down
      regulation of Brachyury expression may play a role in this context.

PMID- 16971392
TI  - Regulation of MAPK-activated protein kinase 5 activity and subcellular
      localization by the atypical MAPK ERK4/MAPK4.
AB  - MAPK-activated protein kinase 5 (MK5) was recently identified as a physiological
      substrate of the atypical MAPK ERK3. Complex formation between ERK3 and MK5
      results in phosphorylation and activation of MK5, concomitant stabilization of
      ERK3, and the nuclear exclusion of both proteins. However, ablation of ERK3 in
      HeLa cells using small interfering RNA or in fibroblasts derived from ERK3 null
      mice reduces the activity of endogenous MK5 by only 50%, suggesting additional
      mechanisms of MK5 regulation. Here we identify the ERK3-related kinase ERK4 as a
      bona fide interaction partner of MK5. Binding of ERK4 to MK5 is accompanied by
      phosphorylation and activation of MK5. Furthermore, complex formation also
      results in the relocalization of MK5 from nucleus to cytoplasm. However unlike
      ERK3, ERK4 is a stable protein, and its half-life is not modified by the presence
      or absence of MK5. Finally, although knock-down of ERK4 protein in HeLa cells
      reduces endogenous MK5 activity by approximately 50%, a combination of small
      interfering RNAs targeting both ERK4 and ERK3 causes a further reduction in the
      MK5 activity by more than 80%. We conclude that MK5 activation is dependent on
      both ERK3 and ERK4 in these cells and that these atypical MAPKs are both
      physiological regulators of MK5 activity.

PMID- 16971393
TI  - Molecular basis for specificity of the extracytoplasmic thioredoxin ResA.
AB  - ResA, an extracytoplasmic thioredoxin from Bacillus subtilis, acts in cytochrome
      c maturation by reducing the disulfide bond present in apocytochromes prior to
      covalent attachment of heme. This reaction is (and has to be) specific, as broad
      substrate specificity would result in unproductive shortcircuiting with the
      general oxidizing thioredoxin(s) present in the same compartment. Using
      mutational analysis and subsequent biochemical and structural characterization of
      active site variants, we show that reduced ResA displays unusually low reactivity
      at neutral pH, consistent with the observed high pKa values>8 for both active
      site cysteines. Residue Glu80 is shown to play a key role in controlling the acid
      base properties of the active site. A model in which substrate binding
      dramatically enhances the reactivity of the active site cysteines is proposed to
      account for the specificity of the protein. Such a substratemediated activation
      mechanism is likely to have wide relevance for extracytoplasmic thioredoxins.

PMID- 16971394
TI  - A decision aid for GPs for the treatment of elderly male patients with lower
      urinary tract symptoms (LUTS).
AB  - BACKGROUND: GPs have four main treatment options for lower urinary tract symptoms
      (LUTS): watchful waiting, alpha-blockers, 5-alpha-reductase inhibitors or
      (referral for) surgery. Guidelines do not provide clear cut-off values for
      (combinations of) symptoms and physical examination results to decide which
      treatment is best. OBJECTIVE: (i) To develop a decision aid ('checklist') for GPs
      for the treatment of patients with LUTS. (ii) To assess its value for use in a
      primary care population. Materials and methods. Population-based cross-sectional
      study. Included were subjects with uncomplicated LUTS for whom treatment in
      primary care may be appropriate. [International Prostate Symptom Score (IPSS) >
      or = 8, no prior prostate surgery, prostate-specific antigen (PSA) value < 10
      ng/ml]. For each subject the appropriateness of surgery and alpha-blocker
      treatment was determined using a previously validated formalized international
      expert panel judgement. Regression models using data available in primary care
      were constructed to predict the panel judgement. Subsequently these models were
      transformed into simple checklists. Finally, the efficiency of these checklists
      was calculated. RESULTS: The best checklists consisted of age, symptoms severity,
      type of symptoms, a quality of life score and PSA value. Assuming one would like
      to provide at least 95% of the subjects for whom a certain treatment is
      appropriate with this treatment (i.e. 'sensitivity' of the checklist > or = 95%),
      one can reach a positive predictive value of 50-60%. CONCLUSION: Simple
      checklists based on the judgement of experts regarding the most appropriate
      therapy can help GPs to advise their patients of a rational treatment strategy.

PMID- 16971395
TI  - Increased cytogenetic damage in a zone in transition from agricultural to
      industrial use: Comprehensive analysis of the micronucleus test in peripheral
      blood lymphocytes.
AB  - A complex situation of chemical exposure has been described in Mexico in a zone
      that is in transition from rural activities towards intensive industrialization,
      which has brought environmental pollution: chloroform, methylene chloride, indigo
      and toluene are some of the pollutants found in the Atoyac and Xochiac rivers. A
      biomonitoring study was planned in order to establish whether there was a
      biological effect due to the environmental situation. Communities where leukaemia
      and thrombocytopenic purpura cases have been reported were included in the study,
      as well as other communities where such cases have not been described. Three
      occupations were distinguished, according to chemical exposure: industrial
      workers, agricultural workers and workers in households, education and commerce.
      A comprehensive analysis in the micronucleus (MN) test was used to study
      genotoxicity biomarkers. Two metabolic polymorphisms were determined, namely,
      glutathione transferase mu1 (GSTM1) and theta1 (GSTT1), which are relevant when
      oxidative responses are involved. Increased genotoxic damage was found, including
      cells with >1 MN, >1 chromatin bud, and nucleoplasmic bridges. The genotoxic
      damage was differentially distributed in the regions studied, being more affected
      those that are closer to the Atoyac and Xochiac rivers, indicating an effect due
      to environmental exposure to the contaminants present in the rivers. Further
      characterization of the exposure regimes in these communities will be done in
      order to contribute to the alleviation of the health risks that environmental
      pollution is posing on the inhabitants of this area.

PMID- 16971396
TI  - The second EURADOS intercomparison of national network systems used to provide
      early warning of a nuclear accident.
AB  - In 1999 and 2002, the EURADOS Working Group on Environmental Monitoring organised
      two European intercomparison exercises of national network systems used to
      provide early warning in case of a nuclear accident. In total, 12 European
      countries, represented by more than 40 scientists, participated in these two
      intercomparisons with more than 35 different dose rate detectors. In addition, an
      in situ gamma spectrometry intercomparison was performed by a group of European
      scientists during the 2002 exercise. Results of these spectrometry measurements
      will be reported elsewhere. This report summarises the results of the second
      intercomparison, performed in 2002, at the environmental dosimetry facilities of
      the Physikalisch-Technische Bundesanstalt (PTB) in Germany. The unique
      combination of the ultra-low background Underground Laboratory (UDO) and two free
      field sites (a floating platform on a lake showing an almost pure cosmic
      radiation field and a free-field gamma ray irradiation facility) provide the
      particular opportunity to precisely quantify the inherent background of the
      detectors and to calibrate them almost free of any background and traceable to
      PTB's primary standards. In addition, the intercomparison comprised
      investigations on the energy and dose rate dependence of the detectors' response
      to gamma radiation as well as on the response to cosmic radiation. Finally, the
      sensitivity of the detector systems to small dose rate variations, similar to
      that caused by a passing overhead radioactive plume, was studied under realistic
      free-field conditions. Following the Council Directive 96/29/EURATOM, the
      participants of the 2002 intercomparison were asked to report their results in
      terms of the operational quantity ambient dose equivalent, H(*)(10). Although the
      verification of the individual calibrations showed smaller discrepancies than
      those in the 1999 intercomparison, in a few cases, these discrepancies would be
      still unacceptably high in the case of a real emergency situation as demonstrated
      by the plume results. This shows the clear need for further efforts towards a
      European harmonisation in environmental dosimetry. For this purpose, a further
      intercomparison shall be held at the PTB in 2006, especially with the
      participation of new members of the European Union.

PMID- 16971397
TI  - Radiation exposure and dose evaluation in intraoral dental radiology.
AB  - In this study, dose area product measurements have been performed to propose
      diagnostic reference levels (DRLs) in intraoral dental radiology. Measurements
      were carried out at 60 X-ray units for all types of intraoral examinations
      performed in clinical routine. The third quartile values calculated range from
      26.2 to 87.0 mGy cm(2). The results showed that there exists a large difference
      between the patient exposures among different dental facilities. It was also
      observed that dentists working with faster film type or higher tube voltage are
      not always associated with lower exposure. The study demonstrated the necessity
      to have the DRLs laid out as guidelines in dental radiology.

PMID- 16971398
TI  - Improving solubility and refolding efficiency of human V(H)s by a novel
      mutational approach.
AB  - The antibody V(H) domains of camelids tend to be soluble and to resist
      aggregation, in contrast to human V(H) domains. For immunotherapy, attempts have
      therefore been made to improve the properties of human V(H)s by camelization of a
      small set of framework residues. Here, we have identified through sequence
      comparison of well-folded llama V(H) domains an alternative set of residues (not
      typically camelid) for mutation. Thus, the solubility and thermal refolding
      efficiency of a typical human V(H), derived from the human antibody BT32/A6, were
      improved by introduction of two mutations in framework region (FR) 1 and 4 to
      generate BT32/A6.L1. Three more mutations in FR3 of BT32/A6.L1 further improved
      the thermal refolding efficiency while retaining solubility and cooperative
      melting profiles. To demonstrate practical utility, BT32/A6.L1 was used to
      construct a phage display library from which were isolated human V(H)s with good
      antigen binding activity and solubility. The engineered human V(H) domains
      described here may be useful for immunotherapy, due to their expected low
      immunogenicity, and in applications involving transient high temperatures, due to
      their efficient refolding after thermal denaturation.

PMID- 16971399
TI  - A novel amyloidogenic transthyretin variant, Gly53Ala, associated with
      intermittent headaches and ataxia.
AB  - We report a novel transthyretin variant, Gly53Ala, in a 44-year-old British woman
      who presented with severe episodic headaches, often with focal neurological
      deficit, before developing progressive ataxia, depression, dementia and
      eventually peripheral neuropathy. Transthyretin amyloidosis was confirmed on
      biopsy of the heart muscle. Serum amyloid P component scintigraphy did not show
      visceral amyloid in extra-cardiac sites, but magnetic resonance imaging indicated
      diffuse leptomeningeal amyloidosis.

PMID- 16971400
TI  - The prevalence of Neisseria gonorrhoeae negative for proline iminopeptidase in
      Asturias, Spain.

PMID- 16971401
TI  - Antibiotic susceptibility of Neisseria gonorrhoeae in Arkhangelsk, Russia.
AB  - OBJECTIVES: To characterise comprehensively the antibiotic susceptibility of
      Neisseria gonorrhoeae in Arkhangelsk, Russia, and to investigate whether the
      recommended treatment guidelines are updated and effective. METHODS: The
      susceptibility of N gonorrhoeae isolates, cultured during June-November 2004
      mainly from consecutive patients with gonorrhoea (n = 76) in Arkhangelsk, to
      penicillin G, ampicillin, cefixime, ceftriaxone, ciprofloxacin, erythromycin,
      azithromycin, kanamycin, spectinomycin and tetracycline was analysed using Etest.
      Nitrocefin discs were used for beta-lactamase detection. RESULTS: The levels of
      intermediate susceptibility and resistance to the different antibiotics were as
      follows: penicillin G 76%, ampicillin 71%, cefixime 0%, ceftriaxone 3%,
      ciprofloxacin 17%, erythromycin 54%, azithromycin 14%, kanamycin 49%,
      spectinomycin 0% and tetracycline 92%. Of the isolates 55 (72%) were determined
      as multiresistant--that is, they showed intermediate susceptibility or resistance
      to three or more classes of antibiotics. However, none of the isolates were beta
      lactamase producing. CONCLUSIONS: In Arkhangelsk, and presumably in many other
      areas of Russia, penicillins, ciprofloxacin, erythromycin, azithromycin,
      kanamycin and tetracycline should not be used in the treatment of gonorrhoea if
      the results of antibiotic susceptibility testing are not available. In Russia,
      optimised, standardised and quality-assured antibiotic susceptibility testing
      needs to be established in many laboratories. Subsequently, continuous local,
      regional and national surveillance of antibiotic susceptibility is crucial to
      detect the emergence of new resistance, monitor changing patterns of
      susceptibility and be able to update treatment recommendations on a regular
      basis.

PMID- 16971402
TI  - Possible reasons for an increase in the proportion of genital ulcers due to
      herpes simplex virus from a cohort of female bar workers in Tanzania.
AB  - OBJECTIVES: To determine trends in the prevalence and aetiological distribution
      of genital ulcer syndrome (GUS) in a cohort of female bar workers and to assess
      factors associated with these trends. METHODS: An open cohort of 600 women at
      high risk of HIV and sexually transmitted infection (STI) was offered screening
      and treatment for STI at 3-month intervals. The prevalence of GUS and associated
      aetiological agents (Herpes simplex virus (HSV), Treponema pallidum and
      Haemophilus ducreyi) were monitored over 27 months through clinical examination,
      dry lesion swabbing and multiplex polymerase chain reaction. The effects of HIV
      status and other factors on the prevalence trends of STI were assessed. RESULTS:
      A total of 753 women were recruited into the cohort over 10 examination rounds.
      At recruitment, the seroprevalence was 67% for HIV and 89% for HSV type 2 (HSV
      2). During follow-up, 57% of ulcers had unknown aetiology, 37% were due to
      genital herpes and 6% to bacterial aetiologies, which disappeared completely in
      later rounds. The absolute prevalence of genital herpes remained stable at around
      2%. The proportion of GUS caused by HSV increased from 22% to 58%, whereas
      bacterial causes declined. These trends were observed in both HIV-negative and
      HIV-positive women. CONCLUSIONS: The changes observed in the frequency and
      proportional distribution of GUS aetiologies suggest that regular STI screening
      and treatment over an extended period can effectively reduce bacterial STI and
      should therefore be sustained. However, in populations with a high prevalence of
      HSV-2, there remains a considerable burden of genital herpes, which soon becomes
      the predominant cause of GUS. Given the observed associations between genital
      herpes and HIV transmission, high priority should be given to the evaluation of
      potential interventions to control HSV-2 either through a vaccine or through
      episodic or suppressive antiviral therapy and primary prevention.

PMID- 16971403
TI  - Saliva is one likely source of leukotriene B4 in exhaled breath condensate.
AB  - Leukotriene (LT)B4 in exhaled breath condensate (EBC) has been reported to be
      elevated in airway inflammation. The origin of leukotrienes in EBC is, however,
      not established. The aims of this study are to measure LTB4 levels in EBC
      collected in two challenges characterised by a strong neutrophilic airway
      inflammation and to compare LTB4 levels in EBC with levels in sputum and saliva.
      LTB4 and alpha-amylase were measured in EBC from 34 healthy subjects exposed in a
      pig confinement building or to a lipopolysaccharide provocation. These markers
      were also measured in induced sputum in 11 of the subjects. For comparison, LTB4
      and alpha-amylase were measured in saliva from healthy subjects. Only four out of
      102 EBC samples had detectable LTB4 (28-100 pg x mL(-1)). alpha-amylase activity
      was detected in the LTB4-positive samples. In contrast, LTB4 was detected in all
      examined sputum supernatants in the same study (median 1,190 pg x mL(-1)). The
      median LTB4 level in saliva was 469 pg x mL(-1). High levels of leukotriene B4 in
      saliva and the presence of leukotriene B4 in exhaled breath condensate only when
      alpha-amylase was detected, indicate that leukotriene B4 found in exhaled breath
      condensate is the result of saliva contamination. As leukotriene B4 was
      consistently present in sputum supernatants, exhaled breath condensate may be
      inappropriate for monitoring airway leukotriene B4.

PMID- 16971404
TI  - Airway neutrophilia in COPD is not associated with increased neutrophil survival.
AB  - Neutrophilic airway inflammation is a prominent feature of chronic obstructive
      pulmonary disease (COPD) and correlates with disease severity. The mechanisms
      that determine the extent of neutrophilia could involve increased influx or
      prolonged survival of neutrophils. The aim of the study was to assess whether
      neutrophil pro-survival mechanisms are increased in the airways of subjects with
      COPD owing to the presence of anti-apoptotic factors in the bronchial lining
      fluid. Induced sputum samples were collected from 20 subjects with stable COPD,
      14 healthy smokers and 14 healthy controls. Quantification of apoptotic
      neutrophils was based on typical morphological cell changes. Anti-apoptotic, pro
      survival activity in the sputum was studied by culturing peripheral blood
      neutrophils with the fluid phase of induced sputum. Apoptosis was assessed both
      by morphology and flow cytometry using Annexin V/7-aminoactinomycin D staining.
      COPD patients and healthy smokers had significantly higher percentages of sputum
      neutrophils than healthy controls. However, there were no significant differences
      between the three subject groups in either the proportion of apoptotic
      neutrophils in sputum or the in vitro anti-apoptotic activity detected in the
      sputum fluid phase. In conclusion, prolonged survival of neutrophils in sputum is
      not a feature of chronic obstructive pulmonary disease and cannot explain the
      increased numbers of airway neutrophils in this disease.

PMID- 16971405
TI  - Genetic determinants of C-reactive protein in COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is associated with a systemic
      inflammatory state, marked by elevations in serum inflammatory markers including
      C-reactive protein (CRP). The present study sought to determine epidemiological
      predictors of CRP levels, to estimate the genetic influence on CRP levels, and to
      identify genetic variants that affect CRP in a family-based study of COPD. CRP
      was measured by a high-sensitivity assay in participants from the Boston Early
      Onset COPD Study. Predictors of CRP level were determined using multilevel linear
      models. Variance component analysis was used to estimate heritability and to
      perform genome-wide linkage analysis for CRP levels. Two variants in the
      surfactant protein B (SFTPB) gene were tested for association with CRP levels.
      Increased age, female sex, higher body mass index, greater smoking pack-yrs and
      reduced forced expiratory volume in one second were all associated with increased
      CRP levels. There was a significant genetic influence on CRP (heritability =
      0.25). Genome-wide linkage analysis revealed several potentially interesting
      chromosomal regions, though no significant evidence for linkage was found. A
      short tandem repeat marker near SFTPB was significantly associated with CRP
      levels. There is a genetic influence on C-reactive protein levels in chronic
      obstructive pulmonary disease patients. Preliminary evidence suggests an
      association of the surfactant protein B gene with systemic inflammation in
      chronic obstructive pulmonary disease.

PMID- 16971406
TI  - Legionella pneumophila-induced NF-kappaB- and MAPK-dependent cytokine release by
      lung epithelial cells.
AB  - Legionella pneumophila causes community-acquired pneumonia with high mortality,
      but little is known about its interaction with the alveolar epithelium. The aim
      of this study was to investigate whether L. pneumophila infection of lung
      epithelial cells (A549) resulted in pro-inflammatory activation. L. pneumophila
      infection induced liberation of interleukin (IL)-2, -4, -6, -8 and -17, monocyte
      chemoattractant protein-1, tumour necrosis factor-alpha, IL-1beta, interferon
      gamma and granulocyte colony-stimulating factor, but not of IL-5, -7, -10, -12
      (p70) or -13 or granulocyte-macrophage colony-stimulating factor. The present
      study focused on IL-8 and found induction by L. pneumophila strains 130b,
      Philadelphia 1, Corby and, to a lesser extent, JR32. Knockout of dotA, a central
      gene involved in type IVB secretion, did not alter IL-8 induction, whereas lack
      of flagellin significantly reduced IL-8 release by Legionella. Moreover, p38
      mitogen-activated protein kinase (MAPK) was activated and kinase inhibition
      reduced secretion of induced cytokines, with the exception of IL-2 and
      granulocyte colony-stimulating factor. In contrast, inhibition of the MAPK kinase
      1/extracellular signal-regulated kinase pathway only reduced the expression of a
      few cytokines. L. pneumophila also induced binding of nuclear factor-kappaB
      subunit RelA/p65 and RNA polymerase II to the il8 promoter, and a specific
      inhibitor of the inhibitor of nuclear factor-kappaB complex dose-dependently
      lowered IL-8 expression. Taken together, Legionella pneumophila activated p38
      mitogen-activated protein kinase- and nuclear factor-kappaB/RelA pathway
      dependent expression of a complex pattern of cytokines by human alveolar
      epithelial cells, presumably contributing to the immune response in
      legionellosis.

PMID- 16971407
TI  - Induction chemotherapy, concurrent chemoradiation and surgery for Pancoast
      tumour.
AB  - The traditional treatment of Pancoast tumour with local approaches (surgery,
      radiotherapy or a combination of both) leads to a poor outcome due to the high
      rate of incomplete resection and the lack of systemic control. The aim of the
      present prospective feasibility study was to determine whether a trimodality
      approach improves local control and survival. Patients with stage IIB-IIIB
      Pancoast tumour received induction chemotherapy (three courses of split-dose
      cisplatin and etoposide or paclitaxel) followed by concurrent chemoradiotherapy
      (a course of cisplatin/etoposide combined with 45 Gy hyperfractionated
      accelerated radiotherapy). After restaging, eligible patients underwent surgery 4
      6 weeks post-radiation. A total of 31 consecutive patients with T3 (81%) or T4
      (19%) Pancoast tumour were enrolled in the study. Induction chemoradiotherapy was
      completed in all patients without treatment-related deaths. Grade 3-4 toxicity
      was observed in 32% of cases. In total, 29 (94%) patients were eligible for
      surgery. Complete resection was achieved in 94% of patients. The post-operative
      mortality rate was 6.4% and major complications arose in 20.6% of the patients.
      The median survival was 54 months with 2- and 5-yr survival rates of 74 and 46%,
      respectively. In conclusion, this intensive multimodality treatment of Pancoast
      tumour is feasible and improves local resectability rates and long-term survival
      as compared with historical series.

PMID- 16971408
TI  - Occupational asthma caused by stainless steel welding fumes: a clinical study.
AB  - The aim of the present study was to describe the cases of occupational asthma
      (OA) due to stainless steel welding fumes diagnosed at the Finnish Institute of
      Occupational Health during the period 1994-2003. OA was diagnosed according to
      patient history, lung function examinations and welding challenge tests with
      measurements of the forced expiratory volume in one second (FEV(1)) and peak
      expiratory flow (PEF) values. The present series comprised 34 patients, all male,
      with a mean age of 44.7 yrs (range 22-57), mainly working as welders. The mean
      duration of exposure was 22.4 yrs, and the mean duration of exposure before the
      onset of respiratory symptoms was 18 yrs. Dyspnoea was the most frequently
      reported work-related respiratory symptom. During the inhalation challenge tests,
      the mode of the asthmatic FEV(1)/PEF reaction was delayed in 16 (47%) patients,
      immediate in nine (26%) patients and dual (both immediate and delayed) in nine
      (26%) patients. In the follow-up assessment 6 months later, only six patients
      were considered able to continue performing welding tasks, whereas occupational
      injury pension was recommended for seven, and measures of vocational
      rehabilitation for 14 patients. In most cases, after the diagnosis of
      occupational asthma, the continuation of welding work was not possible.

PMID- 16971409
TI  - Sex differences in thoracic adaptation to pulmonary hyperinflation in cystic
      fibrosis.
AB  - Sex differences in thoracic adaptation have been reported in patients with cystic
      fibrosis (CF). The interplay between the pattern of thoracic adaptation and the
      function of the respiratory muscles in male and female CF patients with pulmonary
      hyperinflation was investigated. Thoracic dimensions and diaphragm length were
      measured at residual volume, functional residual capacity and total lung capacity
      using chest radiography in 23 CF (12 males) and 18 normal (11 males) subjects.
      Respiratory muscle recruitment during resting breathing was assessed by recording
      intrathoracic and intra-abdominal pressures. In female CF patients, ribcage
      expansion was predominant, tending to preserve diaphragm length. In male CF
      patients, thoracic configuration was normal and diaphragm shortening consequently
      greater. Ribcage cross-sectional area for a given rib inclination was greater in
      CF patients, indicating a structural expansion of the ribcage 2.5 times greater
      in females than males. The contribution of inspiratory ribcage muscles to
      inspiratory pressure was also greater relative to the diaphragm in the CF group.
      In conclusion, a structural expansion of the ribcage occurs in cystic fibrosis
      patients with lung hyperinflation that is greater in females than males. This is
      associated with an apparent greater contribution of inspiratory ribcage muscles
      to inspiratory pressure.

PMID- 16971410
TI  - Tumour necrosis factor and lymphotoxin A polymorphisms and lung function in
      smokers.
AB  - Genetic variants in the tumour necrosis factor (TNF) gene have been investigated
      in chronic obstructive pulmonary disease (COPD). However, there are many
      instances of nonreplication of these associations due to insufficient power or
      other factors. In this study, a large number of subjects were examined to
      elucidate whether genetic variations of TNF and/or lymphotoxin A (LTA), which is
      clustered with TNF, are associated with variations in lung function among
      smokers. The present authors designed two nested case-control studies in the
      National Heart, Lung, and Blood Institute Lung Health Study (LHS), which enrolled
      5,887 smokers. The first design included continuous smokers who had the fastest
      (n = 279) and the slowest (n = 304) decline of lung function during the 5-yr
      follow-up period, and the second included the subjects who had the lowest (n =
      533) and the highest (n = 532) post-bronchodilator % predicted forced expiratory
      volume in one second at the start of the LHS. Within the TNF and LTA region, 10
      tagging single-nucleotide polymorphisms were selected and genotyped. Unlike the
      previous associations between TNF-308 and COPD in Asians, the current study found
      no association between either of the two phenotypes and the LTA and TNF
      polymorphisms. In conclusion, these results support the findings of previous
      studies in late-onset chronic obstructive pulmonary disease in Caucasian
      populations.

PMID- 16971411
TI  - IL18 and IL18R1 polymorphisms, lung CT and fibrosis: A longitudinal study in coal
      miners.
AB  - It has been suggested that interleukin (IL)-18 plays a role in the development of
      inflammatory and fibrosing lung diseases. Associations of polymorphisms in the
      genes coding for IL-18 (IL18 /G-656T, C-607A, G-137C, T113G, C127T) and its
      receptor (IL18R1 /C-69T) with coal workers' pneumoconiosis (CWP) were studied in
      200 miners who were examined in 1990, 1994 and 1999. Coal-dust exposure was
      assessed according to job history and ambient measures. The main health outcome
      was lung computed tomography (CT) score in 1990. Internal coherence was assessed
      by studying CT score in 1994, 4-yr change in CT score and CWP incidence and
      prevalence. CT score in 1990 was a good predictor of radiographic grade in 1999
      and, therefore, an appropriate subclinical quantitative trait. The IL18 -137C
      allele was associated with lower CT score in 1990 and 1994 (1.24 versus 1.69 and
      1.57 versus 2.46, respectively), slower progression of CT score between 1990 and
      1994 and lower pneumoconiosis prevalence in 1999 relative to the G allele (0.33
      versus 0.77 and 8.2 versus 19.6%, respectively). Smoking- or dust-adjustment, and
      stratification on IL18R1 genotype and adjustment for haplotype effects did not
      change the conclusions. In conclusion, the results of the present study suggest a
      role for IL18 in reducing the development of this fibrosing lung disease.

PMID- 16971412
TI  - Use of silicone stents for the management of post-tuberculosis tracheobronchial
      stenosis.
AB  - The role of bronchoscopic management in post-tuberculosis tracheobronchial
      stenosis is not well defined. To investigate the role of bronchoscopic
      intervention, including silicone stenting, in the management of post-tuberculosis
      tracheobronchial stenosis, the current retrospective study was conducted at a
      tertiary referral hospital. Under rigid bronchoscopy, 80 patients underwent
      ballooning, neodymium-yttrium aluminium garnet laser resection and/or
      bougienation as first-line methods of airway dilatation between January 2000 and
      December 2003 inclusive, and were followed for a median of 41 months. Silicone
      stents were required in 75 out of 80 (94%) patients to maintain airway patency.
      Bronchoscopic intervention provided immediate symptomatic relief and improved
      lung function in 88% of the patients. After airway stabilisation, stents were
      removed successfully in 49 out of 75 (65%) patients at a median of 14 months post
      insertion. Three patients out of 75 (4%) eventually underwent surgical
      management. Acute complications included: excessive bleeding (n = 1);
      pneumothorax (n = 5); and pneumomediastinum without mortality (n = 2). Stent
      related late complications, such as migration (51%), granuloma formation (49%),
      mucostasis (19%) and re-stenosis (40%), were controllable during a median follow
      up of 41 months. In conclusion, bronchoscopic intervention, including silicone
      stenting, could be a useful and safe method for treating post-tuberculosis
      tracheobronchial stenosis.

PMID- 16971413
TI  - NT-proBNP reflects right ventricular structure and function in pulmonary
      hypertension.
AB  - The aim of the current study was to investigate whether alterations in N-terminal
      pro brain natriuretic peptide (NT-proBNP) reflect changes in right ventricular
      structure and function in pulmonary hypertension patients during treatment. The
      study consisted of 30 pulmonary hypertension patients; 15 newly diagnosed and 15
      on long-term treatment. NT-proBNP, right heart catheterisation and cardiac
      magnetic resonance imaging measurements were performed, at baseline and follow
      up. There were no significant differences between newly diagnosed patients and
      those on treatment at baseline or follow-up with respect to NT-proBNP,
      haemodynamics and right ventricular parameters. Relative changes in NT-proBNP
      during treatment were correlated to the relative changes in right ventricular end
      diastolic volume index (r = 0.59), right ventricular mass index (r = 0.62) and
      right ventricular ejection fraction (r = -0.81). N-terminal pro brain natriuretic
      peptide measurements reflect changes in magnetic resonance imaging-measured right
      ventricular structure and function in pulmonary hypertension patients. An
      increase in N-terminal pro brain natriuretic peptide over time reflects right
      ventricular dilatation concomitant to hypertrophy and deterioration of systolic
      function.

PMID- 16971414
TI  - Intracellular accumulation of linezolid in Escherichia coli, Citrobacter freundii
      and Enterobacter aerogenes: role of enhanced efflux pump activity and
      inactivation.
AB  - OBJECTIVES: The oxazolidinone class of antibiotics such as linezolid have a
      narrow spectrum of activity that targets Gram-positive bacteria. We hypothesized
      that the poor activity of linezolid in Gram-negative bacteria is in part caused
      by relatively low intracellular concentration due to efflux. METHODS: Using whole
      cell accumulation assays we estimated the intracellular concentration of
      linezolid in Escherichia coli and other Enterobacteriaceae. We included test
      strains with enhanced RND-type multidrug efflux pump activity and with genetic
      inactivation of the pump or functional inhibition by carbonyl cyanide m
      chlorophenylhydrazone as inhibitor of the proton motive force or 1-(1
      naphthylmethyl)-piperazine (NMP), an efflux pump inhibitor. RESULTS: Consistent
      with susceptibility studies, enhanced pump activity caused decreased
      accumulation, and pump inactivation and inhibition caused increased accumulation,
      of linezolid. The accumulation levels in test strains of E. coli, Citrobacter
      freundii and Enterobacter aerogenes with functional pumps were lower than in
      control strains of Staphylococcus aureus and Enterococcus faecium, but were
      higher after pump inactivation and correlated with ethidium bromide and pyronin Y
      accumulation. CONCLUSIONS: The intracellular concentration of linezolid is
      comparatively low owing to efficient efflux of the drug and could be increased
      substantially by inhibition of RND-type efflux pumps.

PMID- 16971415
TI  - Treatment of ESBL-producing Klebsiella pneumoniae bacteraemia with carbapenems or
      flomoxef: a retrospective study and laboratory analysis of the isolates.
AB  - OBJECTIVES: To better understand the clinical outcomes of patients with extended
      spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) bacteraemia
      treated with either flomoxef or a carbapenem, and to evaluate the in vitro
      activities of these antibiotics against ESBL-KP. METHODS: Retrospective analyses
      to identify risk factors for mortality in patients with flomoxef-susceptible ESBL
      KP, especially addressing the therapeutic roles of flomoxef and carbapenem. In
      vitro activities of flomoxef and carbapenem against flomoxef-susceptible ESBL-KP
      isolates were evaluated by susceptibility testing and time-kill study. RESULTS:
      Twenty-seven patients (flomoxef group, n=7; carbapenem group, n=20) were
      included. Clinical severity reflected by high Pitt bacteraemia score (>or=6) was
      an independent risk factor for mortality (OR 13.43; 95% CI, 1.08-166.73;
      P=0.043), while use of flomoxef or a carbapenem was not. The MICs of flomoxef and
      carbapenem indicated that the tested ESBL-KP were susceptible to these
      antibiotics regardless of the inoculum size of 10(5) or 10(7) cfu/mL. Time-kill
      study showed that these antibiotics (flomoxef 8 mg/L and meropenem 4 mg/L) each
      acted actively against and inhibited the regrowth of the tested ESBL-KP for at
      least 24 h. CONCLUSIONS: Flomoxef might be as clinically effective as a
      carbapenem in treating flomoxef-susceptible ESBL-KP bacteraemia.

PMID- 16971416
TI  - Evaluation of dosing regimen of respirable rifampicin biodegradable microspheres
      in the treatment of tuberculosis in the guinea pig.
AB  - OBJECTIVES: The efficacy of rifampicin-loaded polymeric microspheres (RPLGA)
      delivered to guinea pigs infected with Mycobacterium tuberculosis (H37Rv) was
      compared with a daily dose of nebulized rifampicin suspension. METHODS: Aerosol
      infected animals were subjected to multiple dose or single dose treatment with
      RPLGA, PLGA microspheres or micronized rifampicin suspension aerosols. For
      comparison with treatment with suspensions of microspheres, additional groups
      received daily doses of rifampicin-only suspensions for 20 (20-RIF) and 10 (10
      RIF) days. RESULTS: Drug and polymer treated multiple dose groups exhibited
      significantly lower wet lung weights than untreated animals. Spleen wet weights
      and viable bacterial counts (VBCs) were much lower for drug microsphere treated
      animals than for all other groups. In multiple dose studies with rifampicin-only
      suspensions, wet lung weights for 10-RIF and 20-RIF treated animals were much
      smaller than controls. Likewise, wet spleen weights of 10-RIF and 20-RIF treated
      animals were much smaller than controls, consistent with reduced inflammation.
      Spleen VBC of 20-RIF treated animals was much smaller than controls. No
      statistical differences were observed in the lung VBC among single dose groups.
      However, a trend similar to that of the wet weights was observed. CONCLUSIONS:
      Aerosolized RPLGA reduced most measures of tuberculosis (TB) infection. These
      studies are further evidence for the potential of inhaled aerosol therapy for the
      treatment of TB. However, additional studies are required to elucidate underlying
      mechanisms of action and optimize this route of drug delivery.

PMID- 16971417
TI  - pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis clinical
      isolates from the southeast region of Brazil.
AB  - OBJECTIVES: To investigate the presence of mutations in the pncA gene in 31
      pyrazinamide-resistant Mycobacterium tuberculosis and 5 susceptible strains. MICs
      and pyrazinamidase (PZase) activity were also determined. METHODS: All 36 M.
      tuberculosis clinical isolates were genotyped by mycobacterial interspersed
      repetitive units (MIRUs) and most were also typed by spoligotyping. The MIC value
      necessary to inhibit 99% of the resistant mycobacterial isolates was determined
      by microplate Alamar Blue assay (MABA) and by Lowenstein-Jensen assay (LJA). The
      PZase activity was measured by pyrazinamide deamination to pyrazinoic acid and
      ammonia, and the entire pncA sequence including the 410 bp upstream from the
      start codon was determined by DNA sequencing of purified PCR products. RESULTS:
      Of the 31 isolates resistant to pyrazinamide, 26 (83.9%) showed at least one
      mutation in the pncA gene or in its putative regulatory region. Among the 22
      different mutations detected in the pncA gene and in its regulatory region, 9
      (40.9%) mutations (consisting of six substitutions, two insertions and one
      deletion) have not been described in previous studies. Three pyrazinamide
      resistant isolates, confirmed by MIC varying from 800 to 1600 mg/L, carried the
      wild-type pncA sequence and retained PZase activity. CONCLUSIONS: These results
      contribute to the knowledge of the molecular mechanism of pyrazinamide resistance
      in Brazil and also expand the profile of pncA mutations worldwide. The MABA was
      successfully used to determine the MICs of pyrazinamide.

PMID- 16971418
TI  - Endothelial STAT3 is essential for the protective effects of HO-1 in oxidant
      induced lung injury.
AB  - Administering high levels of inspired oxygen, or hyperoxia, is commonly used as a
      life-sustaining measure in critically ill patients. Unfortunately, the oxidant
      stress generated by prolonged hyperoxia can lead to respiratory failure,
      multiorgan failure, and death. Although the endothelial cell is known to be a
      target for hyperoxia-induced injury, its precise role is unclear. Heme oxygenase
      1 (HO-1) and "signal transducer and activator of transcription 3" (STAT3) have
      been found to confer protection against endothelial cell injury. We sought to
      elucidate the specific roles of HO-1 and STAT3 in hyperoxic lung and endothelial
      cell injury. Mice or murine lung endothelial cells (MLEC) administered HO-1 siRNA
      exhibited marked injury and death compared with nonspecific siRNA. Overexpression
      of either HO-1 or STAT3 confers protection. However, HO-1 and its reaction
      product carbon monoxide (CO) lose their protective effects in the presence of
      STAT3 siRNA in MLEC or in endothelial-specific, STAT3-deficient mice. STAT3
      overexpression is able to partially rescue HO-1-deficient MLEC from hyperoxia
      induced cell death. Our results demonstrate 1) the importance of the endothelium
      in lethal hyperoxic injury, 2) HO-1 and CO require endothelial STAT3 for their
      protective effects, and 3) STAT3 confers endothelial cell protection via both HO
      1-dependent and independent mechanisms.

PMID- 16971419
TI  - Three-dimensional conformal radiotherapy for the treatment of arteriovenous
      shunting in patients with hepatocellular carcinoma.
AB  - The objective of this study is to evaluate the efficacy of radiotherapy for the
      treatment of arteriovenous shunting (AVS) in patients with hepatocellular
      carcinoma (HCC). Between November 1997 and April 2005, 20 HCC patients with AVS
      were referred to our department for radiotherapy. The radiation was delivered
      with 10-15 MV X-ray given 5 days per week at 2 approximately 2.5 Gy per fraction.
      Total doses ranged from 45 to 64 Gy (median dose 60 Gy). The patients were
      followed up with color Doppler sonography. When non-invasive imaging suggested
      obliteration, X-ray angiography was performed to verify the results. Four of the
      20 AVS proved to be completely obliterated at X-ray angiography in 1.9, 2.8, 1.8
      and 2.9 months after radiotherapy. One of the remaining 16 showed obvious
      regression on Doppler sonography 0.5 months after radiotherapy, but X-ray
      angiography was not performed to verify the result. Radiation-related hepatic
      failure did not occur during the follow-up period. In conclusion, radiotherapy is
      a treatment alternative for AVS in HCC patients and gives patients with poor
      prognosis the chance to receive further transcatheter arterial embolization.

PMID- 16971420
TI  - A simple processing method allowing comparison of renal enhancing volumes derived
      from standard portal venous phase contrast-enhanced multidetector CT images to
      derive a CT estimate of differential renal function with equivalent results to
      nuclear medicine quantification.
AB  - As iodinated contrast medium is cleared by glomerular filtration, it should be
      possible to apply the same principles utilized in radionuclide studies to derive
      differential renal function by comparison of enhancing renal volumes derived from
      contrast enhanced multidetector CT (CEMDCT). Having established a technique
      iteratively which appeared successful, a retrospective study was performed using
      25 consecutive patients with a wide range of urological conditions who had
      undergone both CEMDCT, including the renal area in the portal venous phase, and
      nuclear medicine (NM) assessment of renal function with no urological
      intervention between the studies. Proprietary volume software was used to
      quantify the volume and attenuation of each kidney, the products of which (after
      subtraction of soft tissue attenuation derived from a region of interest over
      psoas) gave right and left enhancing renal volumes. The contribution by each
      kidney as a percentage of total renal enhancing tissue was derived. Comparison
      with NM studies resulted in excellent correlation of relative renal function by
      CEMDCT and NM assessments having a regression of near unity and a Pearson's
      correlation coefficient of 0.96. Bland Altman and Passing Bablock tests confirmed
      good agreement between the two methods with no bias. This is a simple,
      practicable processing technique using standard portal venous phase CEMDCT images
      to quantify differential function. This technique may allow a one-stop CT
      assessment of both anatomy and function.

PMID- 16971421
TI  - A full-length cDNA infectious clone of North American type 1 porcine reproductive
      and respiratory syndrome virus: expression of green fluorescent protein in the
      Nsp2 region.
AB  - The recent emergence of a unique group of North American type 1 porcine
      reproductive and respiratory syndrome virus (PRRSV) in the United States presents
      new disease control problems for a swine industry that has already been impacted
      seriously by North American type 2 PRRSV. In this study, a full-length cDNA
      infectious clone was generated from a low-virulence North American type 1 PRRSV
      isolate, SD01-08. In vitro studies demonstrated that the cloned virus maintained
      growth properties similar to those of the parental virus. Virological,
      pathological, and immunological observations from animals challenged with cloned
      viruses were similar to those from animals challenged with the parental virus and
      a modified live virus vaccine. To further explore the potential use as a viral
      backbone for expressing foreign genes, the green fluorescent protein (GFP) was
      inserted into a unique deletion site located at amino acid positions 348 and 349
      of the predicted Nsp2 region in the virus, and expression of the Nsp2-GFP fusion
      protein was visualized by fluorescent microscopy. The availability of this North
      American type 1 infectious clone provides an important research tool for further
      study of the basic viral biology and pathogenic mechanisms of this group of type
      1 PRRSV in the United States.

PMID- 16971422
TI  - Molecular epidemiology of the foot-and-mouth disease virus outbreak in the United
      Kingdom in 2001.
AB  - The objective of this study was to quantify the extent to which the genetic
      diversity of foot-and-mouth disease virus (FMDV) arising over the course of
      infection of an individual animal becomes fixed, is transmitted to other animals,
      and thereby accumulates over the course of an outbreak. Complete consensus
      sequences of 23 genomes (each of 8,200 nucleotides) of FMDV were recovered
      directly from epithelium tissue acquired from 21 farms infected over a nearly 7
      month period during the 2001 FMDV outbreak in the United Kingdom. An analysis of
      these consensus sequences revealed very few apparently ambiguous sites but clear
      evidence of 197 nucleotide substitutions at 191 different sites. We estimated the
      rate of nucleotide substitution to be 2.26 x 10(-5) per site per day (95%
      confidence interval [CI], 1.75 x 10(-5) to 2.80 x 10(-5)) and nucleotide
      substitutions to accrue in the consensus sequence at an average rate of 1.5
      substitutions per farm infection. This is a sufficiently high rate showing that
      detailed histories of the transmission pathways can be reliably reconstructed.
      Coalescent methods indicated that the date at which FMDV first infected livestock
      in the United Kingdom was 7 February 2001 (95% CI, 20 January to 19 February
      2001), which was identical to estimates obtained on the basis of purely clinical
      evidence. Nucleotide changes appeared to have occurred evenly across the genome,
      and within the open reading frame, the ratio of nonsynonymous-to-synonymous
      change was 0.09. The ability to recover particular transmission pathways of
      acutely acting RNA pathogens from genetic data will help resolve uncertainties
      about how virus is spread and could help in the control of future epidemics.

PMID- 16971423
TI  - Recombination patterns in aphthoviruses mirror those found in other
      picornaviruses.
AB  - Foot-and-mouth disease virus (FMDV) is thought to evolve largely through genetic
      drift driven by the inherently error-prone nature of its RNA polymerase. There
      is, however, increasing evidence that recombination is an important mechanism in
      the evolution of these and other related picornoviruses. Here, we use an
      extensive set of recombination detection methods to identify 86 unique potential
      recombination events among 125 publicly available FMDV complete genome sequences.
      The large number of events detected between members of different serotypes
      suggests that horizontal flow of sequences among the serotypes is relatively
      common and does not incur severe fitness costs. Interestingly, the distribution
      of recombination breakpoints was found to be largely nonrandom. Whereas there are
      clear breakpoint cold spots within the structural genes, two statistically
      significant hot spots precisely separate these from the nonstructural genes. Very
      similar breakpoint distributions were found for other picornovirus species in the
      genera Enterovirus and Teschovirus. Our results suggest that genome regions
      encoding the structural proteins of both FMDV and other picornaviruses are
      functionally interchangeable modules, supporting recent proposals that the
      structural and nonstructural coding regions of the picornaviruses are evolving
      largely independently of one another.

PMID- 16971424
TI  - The NS1 gene contributes to the virulence of H5N1 avian influenza viruses.
AB  - In the present study, we explored the genetic basis underlying the virulence and
      host range of two H5N1 influenza viruses in chickens. A/goose/Guangdong/1/96
      (GS/GD/1/96) is a highly pathogenic virus for chickens, whereas
      A/goose/Guangdong/2/96 (GS/GD/2/96) is unable to replicate in chickens. These two
      H5N1 viruses differ in sequence by only five amino acids mapping to the PA, NP,
      M1, and NS1 genes. We used reverse genetics to create four single-gene
      recombinants that contained one of the sequence-differing genes from
      nonpathogenic GS/GD/2/96 and the remaining seven gene segments from highly
      pathogenic GS/GD/1/96. We determined that the NS1 gene of GS/GD/2/96 inhibited
      the replication of GS/GD/1/96 in chickens, while the substitution of the PA, NP,
      or M gene did not change the highly pathogenic properties of GS/GD/1/96.
      Conversely, of the recombinant viruses generated in the GS/GD/2/96 background,
      only the virus containing the NS1 gene of GS/GD/1/96 was able to replicate and
      cause disease and death in chickens. The single-amino-acid difference in the
      sequence of these two NS1 genes resides at position 149. We demonstrate that a
      recombinant virus expressing the GS/GD/1/96 NS1 protein with Ala149 is able to
      antagonize the induction of interferon protein levels in chicken embryo
      fibroblasts (CEFs), but a recombinant virus carrying a Val149 substitution is not
      capable of the same effect. These results indicate that the NS1 gene is critical
      for the pathogenicity of avian influenza virus in chickens and that the amino
      acid residue Ala149 correlates with the ability of these viruses to antagonize
      interferon induction in CEFs.

PMID- 16971425
TI  - Requirements for the assembly and release of Newcastle disease virus-like
      particles.
AB  - Paramyxoviruses, such as Newcastle disease virus (NDV), assemble in and bud from
      plasma membranes of infected cells. To explore the role of each of the NDV
      structural proteins in virion assembly and release, virus-like particles (VLPs)
      released from avian cells expressing all possible combinations of the
      nucleoprotein (NP), membrane or matrix protein (M), an uncleaved fusion protein
      (F-K115Q), and hemagglutinin-neuraminidase (HN) protein were characterized for
      densities, protein content, and efficiencies of release. Coexpression of all four
      proteins resulted in the release of VLPs with densities and efficiencies of
      release (1.18 to 1.16 g/cm(3) and 83.8% +/- 1.1%, respectively) similar to those
      of authentic virions. Expression of M protein alone, but not NP, F-K115Q, or HN
      protein individually, resulted in efficient VLP release, and expression of all
      different combinations of proteins in the absence of M protein did not result in
      particle release. Expression of any combination of proteins that included M
      protein yielded VLPs, although with different densities and efficiencies of
      release. To address the roles of NP, F, and HN proteins in VLP assembly, the
      interactions of proteins in VLPs formed with different combinations of viral
      proteins were characterized by coimmunoprecipitation. The colocalization of M
      protein with cell surface F and HN proteins in cells expressing all combinations
      of viral proteins was characterized. Taken together, the results show that M
      protein is necessary and sufficient for NDV budding. Furthermore, they suggest
      that M-HN and M-NP interactions are responsible for incorporation of HN and NP
      proteins into VLPs and that F protein is incorporated indirectly due to
      interactions with NP and HN protein.

PMID- 16971426
TI  - ORF66 protein kinase function is required for T-cell tropism of varicella-zoster
      virus in vivo.
AB  - Several functions have been attributed to the serine/threonine protein kinase
      encoded by open reading frame 66 (ORF66) of varicella-zoster virus (VZV),
      including modulation of the apoptosis and interferon pathways, down-regulation of
      major histocompatibility complex class I cell surface expression, and regulation
      of IE62 localization. The amino acid sequence of the ORF66 protein contains a
      recognizable conserved kinase domain. Point mutations were introduced into
      conserved protein kinase motifs to evaluate their importance to ORF66 protein
      functions. Two substitution mutants were generated, including a G102A
      substitution, which blocked autophosphorylation and altered IE62 localization,
      and an S250P substitution, which had no effect on either autophosphorylation or
      IE62 localization. Both kinase domain mutants grew to titers equivalent to
      recombinant parent Oka (pOka) in vitro. pOka66G102A had slightly reduced growth
      in skin, which was comparable to the reduction observed when ORF66 translation
      was prevented by stop codon insertions in pOka66S. In contrast, infection of T
      cell xenografts with pOka66G102A was associated with a significant decrease in
      infectious virus production equivalent to the impaired T-cell tropism found with
      pOka66S infection of T-cell xenografts in vivo. Disrupting kinase activity with
      the G102A mutation did not alter IE62 cytoplasmic localization in VZV-infected T
      cells, suggesting that decreased T-cell tropism is due to other ORF66 protein
      functions. The G102A mutation reduced the antiapoptotic effects of VZV infection
      of T cells. These experiments indicate that the T-cell tropism of VZV depends
      upon intact ORF66 protein kinase function.

PMID- 16971427
TI  - Inhibition of tRNA3(Lys)-primed reverse transcription by human APOBEC3G during
      human immunodeficiency virus type 1 replication.
AB  - Cells are categorized as being permissive or nonpermissive according to their
      ability to produce infectious human immunodeficiency virus type 1 (HIV-1) lacking
      the viral protein Vif. Nonpermissive cells express the human cytidine deaminase
      APOBEC3G (hA3G), and Vif has been shown to bind to APOBEC3G and facilitate its
      degradation. Vif-negative HIV-1 virions produced in nonpermissive cells
      incorporate hA3G and have a severely reduced ability to produce viral DNA in
      newly infected cells. While it has been proposed that the reduction in DNA
      production is due to hA3G-facilitated deamination of cytidine, followed by DNA
      degradation, we provide evidence here that a decrease in the synthesis of the DNA
      by reverse transcriptase may account for a significant part of this reduction.
      During the infection of cells with Vif-negative HIV-1 produced from 293T cells
      transiently expressing hA3G, much of the inhibition of early (> or =50%
      reduction) and late (> or =95% reduction) viral DNA production, and of viral
      infectivity (> or =95% reduction), can occur independently of DNA deamination.
      The inhibition of the production of early minus-sense strong stop DNA is also
      correlated with a similar inability of tRNA(3)(Lys) to prime reverse
      transcription. A similar reduction in tRNA(3)(Lys) priming and viral infectivity
      is also seen in the naturally nonpermissive cell H9, albeit at significantly
      lower levels of hA3G expression.

PMID- 16971428
TI  - Replication of murine hepatitis virus is regulated by papain-like proteinase 1
      processing of nonstructural proteins 1, 2, and 3.
AB  - Coronaviruses are positive-strand RNA viruses that translate their genome RNA
      into polyproteins that are co- and posttranslationally processed into
      intermediate and mature replicase nonstructural proteins (nsps). In murine
      hepatitis virus (MHV), nsps 1, 2, and 3 are processed by two papain-like
      proteinase activities within nsp3 (PLP1 and PLP2) to yield nsp1, an nsp2-3
      intermediate, and mature nsp2 and nsp3. To determine the role in replication of
      processing between nsp2 and nsp3 at cleavage site 2 (CS2) and PLP1 proteinase
      activity, mutations were engineered into the MHV genome at CS2, at CS1 and CS2,
      and at the PLP1 catalytic site, alone and in combination. Mutant viruses with
      abolished cleavage at CS2 were delayed in growth and RNA synthesis but grew to
      wild-type titers of >10(7) PFU/ml. Mutant viruses with deletion of both CS1 and
      CS2 exhibited both a delay in growth and a decrease in peak viral titer to
      approximately 10(4) PFU/ml. Inactivation of PLP1 catalytic residues resulted in a
      mutant virus that did not process at either CS1 or CS2 and was severely
      debilitated in growth, achieving only 10(2) PFU/ml. However, when both CS1 and
      CS2 were deleted in the presence of inactivated PLP1, the growth of the resulting
      mutant virus was partially compensated, comparable to that of the CS1 and CS2
      deletion mutant. These results demonstrate that interactions of PLP1 with CS1 and
      CS2 are critical for protein processing and suggest that the interactions play
      specific roles in regulation of the functions of nsp1, 2, and 3 in viral RNA
      synthesis.

PMID- 16971429
TI  - Encapsidation determinants located downstream of the major splice donor in the
      maedi-visna virus leader region.
AB  - We investigated the role of the 5'-untranslated region between the primer binding
      site and the gag initiation codon in ovine lentivirus maedi-visna virus (MVV)
      genomic RNA encapsidation. We identified five computer-predicted stem-loops,
      three of which were highly conserved in primary sequence and structure. One
      stable 83-nucleotide (nt) stem-loop (SL4) was not conserved in the primary
      sequence, but phylogenetic analysis revealed several base pair covariations. The
      deletion of individual stem-loops did not markedly affect the relative
      encapsidation efficiency (REE). Only one mutant, carrying a disruption of a 31-nt
      stem-loop (SL5), had 58% REE in fetal ovine synovial (FOS) cells. A 168-nt
      deletion (Delta3MSD) downstream of the major splice donor (MSD) which removed
      three stem-loops, including SL5, resulted in 24% and 20% REE in FOS and 293T
      cells, respectively. A 100-nt deletion (Delta5MSD) upstream of the MSD resulted
      in 15-fold lower cellular genomic RNA levels than the wild-type levels in 293T
      cells. The Delta5MSD mutant and a double mutant (DM) (Delta5MSD and Delta3MSD)
      did not express detectable levels of virion proteins in 293T cells. In contrast,
      the region deleted in Delta5MSD was dispensable in FOS cells, and the DM had the
      same REE as the Delta3MSD virus. Thus, the region upstream of the MSD contains
      sequences critical for RNA and protein expression in a cell type-specific
      fashion. Our results indicate that MVV encapsidation determinants are located
      downstream of the MSD. These results provide comparative insight into lentiviral
      encapsidation and can be utilized in the design of MVV-based gene transfer
      vectors.

PMID- 16971430
TI  - The C-terminal hydrophobic domain of hepatitis C virus RNA polymerase NS5B can be
      replaced with a heterologous domain of poliovirus protein 3A.
AB  - Replication of the plus-stranded RNA genome of hepatitis C virus (HCV) occurs in
      a membrane-bound replication complex consisting of viral and cellular proteins
      and viral RNA. NS5B, the RNA polymerase of HCV, is anchored to the membranes via
      a C-terminal 20-amino-acid-long hydrophobic domain, which is flanked on each side
      by a highly conserved positively charged arginine. Using a genotype 1b subgenomic
      replicon (V. Lohmann, F. Korner, J. O. Koch, U. Herian, L. Theilmann, and R.
      Bartensclager, Science 285:110-113, 1999), we determined the effect of mutations
      of some highly conserved residues in this domain. The replacement of arginine 570
      with alanine completely abolished the colony-forming ability by the replicon,
      while a R591A change was found to be highly detrimental to replication,
      viability, and membrane binding by the mutant NS5B protein. Mutations of two
      other highly conserved amino acids (L588A and P589A) reduced but did not
      eliminate colony formation. It was of interest, if specific amino acid residues
      play a role in membrane anchoring of NS5B and replication, to determine whether a
      complete exchange of the NS5B hydrophobic domain with a domain totally unrelated
      to NS5B would ablate replication. We selected the 22-amino-acid-long hydrophobic
      domain of poliovirus polypeptide 3A that is known to adopt a transmembrane
      configuration, thereby anchoring 3A to membranes. Surprisingly, either partial or
      full replacement of the NS5B hydrophobic domain with the anchor sequences of
      poliovirus polypeptide 3A resulted in the replication of replicons whose colony
      forming abilities were reduced compared to that of the wild-type replicon. Upon
      continued passage of the replicon in Huh-7 cells in the presence of neomycin, the
      replication efficiency of the replicon increased. However, the sequence of the
      poliovirus polypeptide 3A hydrophobic domain, in the context of the subgenomic
      HCV replicon, was stably maintained throughout 40 passages. Our results suggest
      that anchoring NS5B to membranes is necessary but that the amino acid sequence of
      the anchor per se does not require HCV origin. This suggests that specific
      interactions between the NS5B hydrophobic domain and other membrane-bound factors
      may not play a decisive role in HCV replication.

PMID- 16971431
TI  - Mimivirus giant particles incorporate a large fraction of anonymous and unique
      gene products.
AB  - Acanthamoeba polyphaga mimivirus is the largest known virus in both particle size
      and genome complexity. Its 1.2-Mb genome encodes 911 proteins, among which only
      298 have predicted functions. The composition of purified isolated virions was
      analyzed by using a combined electrophoresis/mass spectrometry approach allowing
      the identification of 114 proteins. Besides the expected major structural
      components, the viral particle packages 12 proteins unambiguously associated with
      transcriptional machinery, 3 proteins associated with DNA repair, and 2
      topoisomerases. Other main functional categories represented in the virion
      include oxidative pathways and protein modification. More than half of the
      identified virion-associated proteins correspond to anonymous genes of unknown
      function, including 45 "ORFans." As demonstrated by both Western blotting and
      immunogold staining, some of these "ORFans," which lack any convincing similarity
      in the sequence databases, are endowed with antigenic properties. Thus, anonymous
      and unique genes constituting the majority of the mimivirus gene complement
      encode bona fide proteins that are likely to participate in well-integrated
      processes.

PMID- 16971432
TI  - Live attenuated influenza virus expressing human interleukin-2 reveals increased
      immunogenic potential in young and aged hosts.
AB  - Despite the reported efficacy of commercially available influenza virus vaccines,
      a considerable proportion of the human population does not respond well to
      vaccination. In an attempt to improve the immunogenicity of live influenza
      vaccines, an attenuated, cold-adapted (ca) influenza A virus expressing human
      interleukin-2 (IL-2) from the NS gene was generated. Intranasal immunization of
      young adult and aged mice with the IL-2-expressing virus resulted in markedly
      enhanced mucosal and cellular immune responses compared to those of mice
      immunized with the nonrecombinant ca parent strain. Interestingly, the mucosal
      immunoglobulin A (IgA) and CD8(+) T-cell responses in the respiratory compartment
      could be restored in aged mice primed with the IL-2-expressing virus to
      magnitudes similar to those in young adult mice. The immunomodulating effect of
      locally expressed IL-2 also gave rise to a systemic CD8(+) T-cell and distant
      urogenital IgA response in young adult mice, but this effect was less distinct in
      aged mice. Importantly, only mice immunized with the recombinant IL-2 virus were
      completely protected from a pathogenic wild-type virus challenge and revealed a
      stronger onset of virus-specific CD8(+) T-cell recall response. Our findings
      emphasize the potential of reverse genetics to improve the efficacy of live
      influenza vaccines, thus rendering them more suitable for high-risk age groups.

PMID- 16971433
TI  - The hepatitis C virus RNA 3'-untranslated region strongly enhances translation
      directed by the internal ribosome entry site.
AB  - The positive-strand RNA genome of the hepatitis C virus (HCV) is flanked by 5'-
      and 3'-untranslated regions (UTRs). Translation of the viral RNA is directed by
      the internal ribosome entry site (IRES) in the 5'-UTR, and subsequent viral RNA
      replication requires sequences in the 3'-UTR and in the 5'-UTR. Addressing
      previous conflicting reports on a possible function of the 3'-UTR for RNA
      translation in this study, we found that reporter construct design is an
      important parameter in experiments testing 3'-UTR function. A translation
      enhancer function of the HCV 3'-UTR was detected only after transfection of
      monocistronic reporter RNAs or complete RNA genomes having a 3'-UTR with a
      precise 3' terminus. The 3'-UTR strongly stimulates HCV IRES-dependent
      translation in human hepatoma cell lines but only weakly in nonliver cell lines.
      The variable region, the poly(U . C) tract, and the most 3' terminal stem-loop 1
      of the highly conserved 3' X region contribute significantly to translation
      enhancement, whereas stem-loops 2 and 3 of the 3' X region are involved only to a
      minor extent. Thus, the signals for translation enhancement and for the
      initiation of RNA minus-strand synthesis in the HCV 3'-UTR partially overlap,
      supporting the idea that these sequences along with viral and possibly also
      cellular factors may be involved in an RNA 3'-5' end interaction and a switch
      between translation and RNA replication.

PMID- 16971434
TI  - Genetic and neutralization properties of subtype C human immunodeficiency virus
      type 1 molecular env clones from acute and early heterosexually acquired
      infections in Southern Africa.
AB  - A standard panel of subtype C human immunodeficiency virus type 1 (HIV-1) Env
      pseudotyped viruses was created by cloning, sequencing, and characterizing
      functional gp160 genes from 18 acute and early heterosexually acquired infections
      in South Africa and Zambia. In general, the gp120 region of these clones was
      shorter (most evident in V1 and V4) and less glycosylated compared to newly
      transmitted subtype B viruses, and it was underglycosylated but no different in
      length compared to chronic subtype C viruses. The gp120s also exhibited low amino
      acid sequence variability (12%) in V3 and high variability (39%) immediately
      downstream of V3, a feature shared with newly transmitted subtype B viruses and
      chronic viruses of both subtypes. When tested as Env-pseudotyped viruses in a
      luciferase reporter gene assay, all clones possessed an R5 phenotype and
      resembled primary isolates in their sensitivity to neutralization by HIV-1
      positive plasmas. Results obtained with a multisubtype plasma panel suggested
      partial subtype preference in the neutralizing antibody response to infection.
      The clones were typical of subtype C in that all were resistant to 2G12
      (associated with loss of N-glycosylation at position 295) and most were resistant
      to 2F5, but all were sensitive to 4E10 and many were sensitive to immunoglobulin
      G1b12. Finally, conserved neutralization epitopes in the CD4-induced coreceptor
      binding domain of gp120 were poorly accessible and were difficult to induce and
      stabilize with soluble CD4 on Env-pseudotyped viruses. These results illustrate
      key genetic and antigenic properties of subtype C HIV-1 that might impact the
      design and testing of candidate vaccines. A subset of these gp160 clones are
      suitable for use as reference reagents to facilitate standardized assessments of
      vaccine-elicited neutralizing antibody responses.

PMID- 16971435
TI  - Cellular immune responses in children and adults receiving inactivated or live
      attenuated influenza vaccines.
AB  - The patterns of cellular immune responses induced by live attenuated influenza
      vaccine (LAIV) versus those of the trivalent inactivated influenza vaccine (TIV)
      have not been studied extensively, especially in children. The goals of this
      study were to evaluate the effects of TIV and LAIV immunization on cellular
      immunity to live influenza A virus in children and adults and to explore factors
      associated with variations in responses to influenza vaccines among individuals.
      A gamma interferon (IFN-gamma) flow cytometry assay was used to measure IFN-gamma
      producing (IFN-gamma+) NK and T cells in peripheral blood mononuclear cell
      cultures stimulated with a live influenza A virus strain before and after LAIV or
      TIV immunization of children and adults. The mean percentages of influenza A
      virus-specific IFN-gamma+ CD4 and CD8 T cells increased significantly after LAIV,
      but not TIV, immunization in children aged 5 to 9 years. No increases in the mean
      levels of influenza A virus-reactive IFN-gamma+ T cells and NK cells were
      observed in adults given LAIV or TIV. TIV induced a significant increase in
      influenza A virus-reactive T cells in 6-month- to 4-year-old children; LAIV was
      not evaluated in this age group. The postvaccination changes (n-fold) in the
      percentages of influenza A virus-reactive IFN-gamma+ T and NK cells in adults
      were highly variable and correlated inversely with the prevaccination
      percentages, in particular with that of the CD56(dim) NK cell subset. In
      conclusion, our findings identify age, type of vaccine, and prevaccination levels
      of immune reactivity to influenza A virus as factors significantly associated
      with the magnitude of cellular immune responses to influenza vaccines.

PMID- 16971436
TI  - The NPro product of bovine viral diarrhea virus inhibits DNA binding by
      interferon regulatory factor 3 and targets it for proteasomal degradation.
AB  - Bovine viral diarrhea virus (BVDV) is a pestivirus that can establish a
      persistent infection in the developing fetus and has the ability to disable the
      production of type I interferon. In this report, we extend our previous
      observations that BVDV encodes a protein able to specifically block the activity
      of interferon regulatory factor 3 (IRF-3), a transcription factor essential for
      interferon promoter activation, by demonstrating that this is a property of the N
      terminal protease fragment (NPro) of the BVDV polyprotein. Although BVDV
      infections cause relocalization of cellular IRF-3 from the cytoplasm to the
      nucleus early in infection, NPro blocks IRF-3 from binding to DNA. NPro has the
      additional property of targeting IRF-3 for polyubiquitination and subsequent
      destruction by cellular multicatalytic proteasomes. The autoprotease activity of
      NPro is not required for the inhibition of type I interferon induction or the
      targeting of IRF-3 for degradation.

PMID- 16971437
TI  - Structurally mapping the diverse phenotype of adeno-associated virus serotype 4.
AB  - The adeno-associated viruses (AAVs) can package and deliver foreign DNA into
      cells for corrective gene delivery applications. The AAV serotypes have distinct
      cell binding, transduction, and antigenic characteristics that have been shown to
      be dictated by the capsid viral protein (VP) sequence. To understand the
      contribution of capsid structure to these properties, we have determined the
      crystal structure of AAV serotype 4 (AAV4), one of the most diverse serotypes
      with respect to capsid protein sequence and antigenic reactivity. Structural
      comparison of AAV4 to AAV2 shows conservation of the core beta strands (betaB to
      betaI) and helical (alphaA) secondary structure elements, which also exist in all
      other known parvovirus structures. However, surface loop variations (I to IX),
      some containing compensating structural insertions and deletions in adjacent
      regions, result in local topological differences on the capsid surface. These
      include AAV4 having a deeper twofold depression, wider and rounder protrusions
      surrounding the threefold axes, and a different topology at the top of the
      fivefold channel from that of AAV2. Also, the previously observed "valleys"
      between the threefold protrusions, containing AAV2's heparin binding residues,
      are narrower in AAV4. The observed differences in loop topologies at subunit
      interfaces are consistent with the inability of AAV2 and AAV4 VPs to combine for
      mosaic capsid formation in efforts to engineer novel tropisms. Significantly, all
      of the surface loop variations are associated with amino acids reported to affect
      receptor recognition, transduction, and anticapsid antibody reactivity for AAV2.
      This observation suggests that these capsid regions may also play similar roles
      in the other AAV serotypes.

PMID- 16971438
TI  - E6/E7 expression of human papillomavirus type 20 (HPV-20) and HPV-27 influences
      proliferation and differentiation of the skin in UV-irradiated SKH-hr1 transgenic
      mice.
AB  - The functional role of UV irradiation, in combination with the E6 and E7 proteins
      of the cutaneous human papillomavirus (HPV) types in the malignant conversion of
      benign papillomatous lesions, has not been elucidated. Transgenic SKH-hr1
      hairless mice expressing HPV-20 and HPV-27 E6 and E7 proteins in the suprabasal
      compartment were generated and exposed to chronic UV irradiation. Histological
      and immunohistochemical examination of skin samples revealed enhanced
      proliferation of the epidermal layers and papilloma formation in both transgenic
      strains in comparison to what was observed with nontransgenic mice. Squamous cell
      carcinoma developed in the HPV-20 E6/E7 transgenic line as well as in the HPV-27
      E6/E7 transgenic line. Several weeks after cessation of UV-B exposure, enhanced
      proliferation, as measured by BrdU incorporation, was maintained only in HPV-20
      transgenic skin. Keratin 6 expression was increased in the transgenic mice
      throughout all cell layers. Expression of the differentiation markers involucrin
      and loricrin was reduced and disturbed. p63alpha expression was differentially
      regulated with high levels of cytoplasmic expression in clusters of cells in the
      granular layer of the skin in the transgenic lines 20 weeks after cessation of UV
      B exposure, in contrast to uninterrupted staining in the nontransgenic lines. p53
      was expressed in clusters of cells in nontransgenic and HPV-27 transgenic mice,
      in contrast to an even distribution in a higher number of cells in HPV-20
      transgenic animals.

PMID- 16971439
TI  - Two modes of herpesvirus trafficking in neurons: membrane acquisition directs
      motion.
AB  - Alphaherpesvirus infection of the mammalian nervous system is dependent upon the
      long-distance intracellular transport of viral particles in axons. How viral
      particles are effectively trafficked in axons to either sensory ganglia following
      initial infection or back out to peripheral sites of innervation following
      reactivation remains unknown. The mechanism of axonal transport has, in part,
      been obscured by contradictory findings regarding whether capsids are transported
      in axons in the absence of membrane components or as enveloped virions. By
      imaging actively translocated viral structural components in living peripheral
      neurons, we demonstrate that herpesviruses use two distinct pathways to move in
      axons. Following entry into cells, exposure of the capsid to the cytosol resulted
      in efficient retrograde transport to the neuronal cell body. In contrast, progeny
      virus particles moved in the anterograde direction following acquisition of
      virion envelope proteins and membrane lipids. Retrograde transport was
      effectively shut down in this membrane-bound state, allowing for efficient
      delivery of progeny viral particles to the distal axon. Notably, progeny viral
      particles that lacked a membrane were misdirected back to the cell body. These
      findings show that cytosolic capsids are trafficked to the neuronal cell body and
      that viral egress in axons occurs after capsids are enshrouded in a membrane
      envelope.

PMID- 16971440
TI  - Oligomerization of hepatitis C virus core protein is crucial for interaction with
      the cytoplasmic domain of E1 envelope protein.
AB  - Hepatitis C virus (HCV) contains two membrane-associated envelope glycoproteins,
      E1 and E2, which assemble as a heterodimer in the endoplasmic reticulum (ER). In
      this study, predictive algorithms and genetic analyses of deletion mutants and
      glycosylation site variants of the E1 glycoprotein were used to suggest that the
      glycoprotein can adopt two topologies in the ER membrane: the conventional type I
      membrane topology and a polytopic topology in which the protein spans the ER
      membrane twice with an intervening cytoplasmic loop (amino acid residues 288 to
      360). We also demonstrate that the E1 glycoprotein is able to associate with the
      HCV core protein, but only upon oligomerization of the core protein in the
      presence of tRNA to form capsid-like structures. Yeast two-hybrid and
      immunoprecipitation analyses reveal that oligomerization of the core protein is
      promoted by amino acid residues 72 to 91 in the core. Furthermore, the
      association between the E1 glycoprotein and the assembled core can be
      recapitulated using a fusion protein containing the putative cytoplasmic loop of
      the E1 glycoprotein. This fusion protein is also able to compete with the intact
      E1 glycoprotein for binding to the core. Mutagenesis of the cytoplasmic loop of
      E1 was used to define a region of four amino acids (residues 312 to 315) that is
      important for interaction with the assembled HCV core. Taken together, our
      studies suggest that interaction between the self-oligomerized HCV core and the
      E1 glycoprotein is mediated through the cytoplasmic loop present in a polytopic
      form of the E1 glycoprotein.

PMID- 16971441
TI  - Translation of the flavivirus kunjin NS3 gene in cis but not its RNA sequence or
      secondary structure is essential for efficient RNA packaging.
AB  - Our previous studies using trans-complementation analysis of Kunjin virus (KUN)
      full-length cDNA clones harboring in-frame deletions in the NS3 gene demonstrated
      the inability of these defective complemented RNAs to be packaged into virus
      particles (W. J. Liu, P. L. Sedlak, N. Kondratieva, and A. A. Khromykh, J. Virol.
      76:10766-10775). In this study we aimed to establish whether this requirement for
      NS3 in RNA packaging is determined by the secondary RNA structure of the NS3 gene
      or by the essential role of the translated NS3 gene product. Multiple silent
      mutations of three computer-predicted stable RNA structures in the NS3 coding
      region of KUN replicon RNA aimed at disrupting RNA secondary structure without
      affecting amino acid sequence did not affect RNA replication and packaging into
      virus-like particles in the packaging cell line, thus demonstrating that the
      predicted conserved RNA structures in the NS3 gene do not play a role in RNA
      replication and/or packaging. In contrast, double frameshift mutations in the NS3
      coding region of full-length KUN RNA, producing scrambled NS3 protein but
      retaining secondary RNA structure, resulted in the loss of ability of these
      defective RNAs to be packaged into virus particles in complementation experiments
      in KUN replicon-expressing cells. Furthermore, the more robust complementation
      packaging system based on established stable cell lines producing large amounts
      of complemented replicating NS3-deficient replicon RNAs and infection with KUN
      virus to provide structural proteins also failed to detect any secreted virus
      like particles containing packaged NS3-deficient replicon RNAs. These results
      have now firmly established the requirement of KUN NS3 protein translated in cis
      for genome packaging into virus particles.

PMID- 16971442
TI  - Assembly of highly infectious rotavirus particles recoated with recombinant outer
      capsid proteins.
AB  - Assembly of the rotavirus outer capsid is the final step of a complex pathway. In
      vivo, the later steps include a maturational membrane penetration that is
      dependent on the scaffolding activity of a viral nonstructural protein. In vitro,
      simply adding the recombinant outer capsid proteins VP4 and VP7 to authentic
      double-layered rotavirus subviral particles (DLPs) in the presence of calcium and
      acidic pH increases infectivity by a factor of up to 10(7), yielding particles as
      infectious as authentic purified virions. VP4 must be added before VP7 for high
      level infectivity. Steep dependence of infectious recoating on VP4 concentration
      suggests that VP4-VP4 interactions, probably oligomerization, precede VP4 binding
      to particles. Trypsin sensitivity analysis identifies two populations of VP4
      associated with recoated particles: properly mounted VP4 that can be specifically
      primed by trypsin, and nonspecifically associated VP4 that is degraded by
      trypsin. A full complement of properly assembled VP4 is not required for
      efficient infectivity. Minimal dependence of recoating on VP7 concentration
      suggests that VP7 binds DLPs with high affinity. The parameters for efficient
      recoating and the characterization of recoated particles suggest a model in
      which, after a relatively weak interaction between oligomeric VP4 and DLPs, VP7
      binds the particles and locks VP4 in place. Recoating will allow the use of
      infectious modified rotavirus particles to explore rotavirus assembly and cell
      entry and could lead to practical applications in novel immunization strategies.

PMID- 16971443
TI  - Multivalent sequence recognition by Epstein-Barr virus Zta requires cysteine 171
      and an extension of the canonical B-ZIP domain.
AB  - Epstein-Barr virus (EBV) immediate-early protein Zta is a member of the basic
      leucine zipper (B-ZIP) family of DNA binding proteins that has an unusual
      capacity to recognize multiple DNA recognition sites, including AP-1 and C/EBP
      binding sites. To better understand the structure and function of Zta, we have
      mutagenized cysteine residues within or adjacent to the B-ZIP domain. We found
      that serine substitution for cysteine 171 (C171S), which lies outside and amino
      terminal to the B-ZIP basic region, completely abrogates Zta capacity to initiate
      lytic cycle replication. C171S disrupted Zta transcription activation function of
      several EBV lytic cycle promoters, including the BMRF1 gene (EA-D) and the other
      lytic activator, Rta. Overexpression of Rta could not rescue the C171S defect for
      transcription reactivation or viral DNA replication. Zta C171S was defective for
      binding to these promoters in vivo, as measured by chromatin immunoprecipitation
      assay. Purified Zta C171S bound AP-1 sites similar to wild-type Zta, but it was
      incapable of binding several degenerate Zta sites, including a consensus C/EBP
      site. Zta truncation mutations reveal that residues N terminal to the B-ZIP
      (amino acids 156 to 178) confer C/EBP binding capacity to the otherwise AP-1
      restricted DNA recognition function. Comparison among viral orthologues of Zta
      suggest that a conserved N-terminal extension of the consensus B-ZIP domain is
      required for this multivalent DNA recognition capacity of Zta and is essential
      for viral reactivation.

PMID- 16971445
TI  - Hantavirus N protein exhibits genus-specific recognition of the viral RNA
      panhandle.
AB  - A key genomic characteristic that helps define Hantavirus as a genus of the
      family Bunyaviridae is the presence of distinctive terminal complementary
      nucleotides that promote the folding of the viral genomic segments into
      "panhandle" hairpin structures. The hantavirus nucleocapsid protein (N protein),
      which is encoded by the smallest of the three negative-sense genomic RNA
      segments, undergoes in vivo and in vitro trimerization. Trimeric hantavirus N
      protein specifically recognizes the panhandle structure formed by complementary
      base sequence of 5' and 3' ends of viral genomic RNA. N protein trimers from the
      Andes, Puumala, Prospect Hill, Seoul, and Sin Nombre viruses recognize their
      individual homologous panhandles as well as other hantavirus panhandles with high
      affinity. In contrast, these hantavirus N proteins bind with markedly reduced
      affinity to the panhandles from the genera Bunyavirus, Tospovirus, and
      Phlebovirus or Nairovirus. Interactions between most hantavirus N and
      heterologous hantavirus viral RNA panhandles are mediated by the nine terminal
      conserved nucleotides of the panhandle, whereas Sin Nombre virus N requires the
      first 23 nucleotides for high-affinity binding. Trimeric hantavirus N complexes
      undergo a prominent conformational change while interacting with panhandles from
      members of the genus Hantavirus but not while interacting with panhandles from
      viruses of other genera of the family Bunyaviridae. These data indicate that high
      affinity interactions between trimeric N and hantavirus panhandles are conserved
      within the genus Hantavirus.

PMID- 16971444
TI  - Cross-protection against a human enteric coronavirus and a virulent bovine
      enteric coronavirus in gnotobiotic calves.
AB  - A group 2 human coronavirus designated HECV-4408 was isolated from a child with
      acute diarrhea and is antigenically and genetically more closely related to
      bovine coronavirus (BCoV) than to human coronavirus OC43 (X. M. Zhang, W. Herbst,
      K. G. Kousoulas, and J. Storz, J. Med. Virol. 44:152-161, 1994). To determine
      whether HECV-4408 infects gnotobiotic calves and induces cross-protective
      immunity against the virulent enteric BCoV DB2 strain, gnotobiotic calves (n = 4)
      were orally inoculated with HECV-4408 and then challenged with BCoV DB2 at
      postinoculation day (PID) 21. All calves inoculated with HECV-4408 developed
      diarrhea at PID 3 to 4 lasting 5 to 9 days. Fecal and nasal virus shedding were
      first detected by reverse transcription-PCR at PID 3 to 4 and at PID 2 to 4,
      respectively. After challenge with bovine coronavirus, no diarrhea or virus
      shedding was detected in calves inoculated with HECV-4408, but a mock-inoculated
      calf developed diarrhea and fecal and nasal shedding. Fecal immunoglobulin A
      (IgA) and serum IgG antibodies were first detected at PID 7 and PID 14,
      respectively. At postchallenge day 7, serum IgG and fecal IgA antibody titers
      remained the same or increased only twofold compared to prechallenge titers. An
      additional two gnotobiotic calves were inoculated with HECV-4408 and euthanized
      at PID 5. Moderate villous atrophy was observed in the small intestines, and
      viral antigen was detected in villous enterocytes of the small and large
      intestines by immunohistochemistry. These results support and extend the previous
      report that HECV-4408 is likely a variant of bovine coronavirus. They confirm its
      infectivity for calves and complete cross-protection against a bovine coronavirus
      (DB2 strain) showing 98.2% amino acid identity to HECV-4408 in the S protein.

PMID- 16971446
TI  - A high-throughput method for cloning and sequencing human immunodeficiency virus
      type 1 integration sites.
AB  - Integration of retroviral DNA is nonspecific and can occur at many sites
      throughout chromosomes. However, the process is not uniformly distributed, and
      both hot and cold spots for integration exist. The mechanism that determines
      target site specificity is not well understood. Because of the nonspecific and
      widespread nature of integration, studies analyzing the mechanism and factors
      that control target site selection require the collection and analysis of a large
      library of human immunodeficiency virus type 1 (HIV-1) proviral clones. Such
      analyses are time-consuming and labor-intensive using conventional means. We have
      developed an efficient and high-throughput method of sequencing and mapping a
      large number of independent integration sites in the absence of any selection or
      bias. The new assay involves the use of a modified HIV-1 (NL-Mme) containing a
      type IIS restriction site, MmeI, at the right end of viral DNA. Digestion of
      genomic DNA from NL-Mme-infected cells generated viral DNA-containing fragments
      of a discrete size. Subsequent ligation-mediated PCR yielded short integration
      site fragments termed Int-tags, which were concatemerized for determining
      multiple integration sites in a single sequencing reaction. Analysis of
      chromosomal features and sequence preference associated with integration events
      confirmed the validity of the new high-throughput assay. The assay will aid the
      effort in understanding the mechanisms of target site selection during HIV-1 DNA
      integration, and the described methodology can be adapted easily to integration
      site studies involving other retroviruses and transposons.

PMID- 16971447
TI  - Functions of the stem region of the Semliki Forest virus fusion protein during
      virus fusion and assembly.
AB  - Membrane fusion of the alphaviruses is mediated by the E1 protein, a class II
      virus membrane fusion protein. During fusion, E1 dissociates from its heterodimer
      interaction with the E2 protein and forms a target membrane-inserted E1
      homotrimer. The structure of the homotrimer is that of a trimeric hairpin in
      which E1 domain III and the stem region fold back toward the target membrane
      inserted fusion peptide loop. The E1 stem region has a strictly conserved length
      and several highly conserved residues, suggesting the possibility of specific
      stem interactions along the trimer core and an important role in driving membrane
      fusion. Mutagenesis studies of the alphavirus Semliki Forest virus (SFV) here
      demonstrated that there was a strong requirement for the E1 stem in virus
      assembly and budding, probably reflecting its importance in lateral interactions
      of the envelope proteins. Surprisingly, however, neither the conserved length nor
      any specific residues of the stem were required for membrane fusion. Although the
      highest fusion activity was observed with wild-type E1, efficient fusion was
      mediated by stem mutants containing a variety of substitutions or deletions. A
      minimal stem length was required but could be conferred by a series of alanine
      residues. The lack of a specific stem sequence requirement during SFV fusion
      suggests that the interaction of domain III with the trimer core can provide
      sufficient driving force to mediate membrane merger.

PMID- 16971448
TI  - Prevalence and phylogeny of Kakugo virus, a novel insect picorna-like virus that
      infects the honeybee (Apis mellifera L.), under various colony conditions.
AB  - We previously identified a novel insect picorna-like virus, termed Kakugo virus
      (KV), from the brains of aggressive worker honeybees that had counterattacked a
      giant hornet. To survey the prevalence of KV in worker populations engaged in
      various labors, we quantified KV genomic RNA. KV was detected specifically from
      aggressive workers in some colonies, while it was also detected from other worker
      populations in other colonies where the amount of KV detected in the workers was
      relatively high, suggesting that KV can infect various worker populations in the
      honeybee colonies. To investigate whether the KV strains detected were identical,
      phylogenetic analysis was performed. There was less than a 2% difference in the
      RNA-dependent RNA polymerase (RdRp) sequences between KV strains from aggressive
      workers and those from other worker populations, suggesting that all of the
      viruses detected were virtually the same KV. We also found that some of the KV
      infected colonies were parasitized by Varroa mites, and the sequences of the KV
      strains detected from the mites were the same as those detected from the workers
      of the same colonies, suggesting that the mites mediate KV prevalence in the
      honeybee colonies. KV strains had approximately 6% and 15% sequence differences
      in the RdRp region from deformed wing virus and Varroa destructor virus 1,
      respectively, suggesting that KV represents a viral strain closely related to,
      but distinct from, these two viruses.

PMID- 16971449
TI  - Selection of early-occurring mutations dictates hormone-independent progression
      in mouse mammary tumor lines.
AB  - Mice harboring three mouse mammary tumor virus (MMTV) variants develop pregnancy
      dependent (PD) tumors that progress to pregnancy-independent (PI) behavior
      through successive passages. Herein, we identified 10 predominant insertions in
      PI transplants from 8 independent tumor lines. These mutations were also detected
      in small cell populations in the early PD passages. In addition, we identified a
      new viral insertion upstream of the gene Rspo3, which is overexpressed in three
      of the eight independent tumor lines and codes for a protein very similar to the
      recently described protein encoded by Int7. This study suggests that during
      progression towards hormone independence, clonal expansion of cells with specific
      mutations might be more relevant than the occurrence of new MMTV insertions.

PMID- 16971450
TI  - Herpes simplex virus capsids are transported in neuronal axons without an
      envelope containing the viral glycoproteins.
AB  - Electron micrographic studies of neuronal axons have produced contradictory
      conclusions on how alphaherpesviruses are transported from neuron cell bodies to
      axon termini. Some reports have described unenveloped capsids transported on
      axonal microtubules with separate transport of viral glycoproteins within
      membrane vesicles. Others have observed enveloped virions in proximal and distal
      axons. We characterized transport of herpes simplex virus (HSV) in human and rat
      neurons by staining permeabilized neurons with capsid- and glycoprotein-specific
      antibodies. Deconvolution microscopy was used to view 200-nm sections of axons.
      HSV glycoproteins were very rarely associated with capsids (3 to 5%) and vice
      versa. Instances of glycoprotein/capsid overlap frequently involved nonconcentric
      puncta and regions of axons with dense viral protein concentrations. Similarly,
      HSV capsids expressing a VP26-green fluorescent protein fusion protein (VP26/GFP)
      did not stain with antiglycoprotein antibodies. Live-cell imaging experiments
      with VP26/GFP-labeled capsids demonstrated that capsids moved in a saltatory
      fashion, and very few stalled for more than 1 to 2 min. To determine if capsids
      could be transported down axons without glycoproteins, neurons were treated with
      brefeldin A (BFA). However, BFA blocked both capsid and glycoprotein transport.
      Glycoproteins were transported into and down axons normally when neurons were
      infected with an HSV mutant that produces immature capsids that are retained in
      the nucleus. We concluded that HSV capsids are transported in axons without an
      envelope containing viral glycoproteins, with glycoproteins transported
      separately and assembling with capsids at axon termini.

PMID- 16971451
TI  - hsp72, a host determinant of measles virus neurovirulence.
AB  - Transient hyperthermia such as that experienced during febrile episodes increases
      expression of the major inducible 70-kDa heat shock protein (hsp72). Despite the
      relevance of febrile episodes to viral pathogenesis and the multiple in vitro
      roles of heat shock proteins in viral replication and gene expression, the in
      vivo significance of virus-heat shock protein interactions is unknown. The
      present work determined the in vivo relationship between hsp72 levels and
      neurovirulence of an hsp72-responsive virus using the mouse model of measles
      virus (MV) encephalitis. Transgenic C57BL/6 mice were created to constitutively
      overexpress hsp72 in neurons, and these mice were inoculated intracranially with
      Edmonston MV (Ed MV) at 42 h of age. The mean viral RNA burden in brain was
      approximately 2 orders of magnitude higher in transgenic animals than in
      nontransgenic animals 2 to 4 weeks postinfection, and this increased burden was
      associated with a fivefold increase in mortality. Mice were also challenged with
      an Ed MV variant exhibiting an attenuated in vitro response to hsp72-dependent
      stimulation of viral transcription (Ed N-522D). This virus exhibited an
      attenuated neuropathogenicity in transgenic mice, where mortality and viral RNA
      burdens were not significantly different from nontransgenic mice infected with
      either Ed N-522D or parent Ed MV. Collectively, these results indicate that hsp72
      levels can serve as a host determinant of viral neurovirulence in C57BL/6 mice,
      reflecting the direct influence of hsp72 on viral gene expression.

PMID- 16971452
TI  - Characterization of human metapneumovirus F protein-promoted membrane fusion:
      critical roles for proteolytic processing and low pH.
AB  - Human metapneumovirus (HMPV) is a recently described human pathogen of the
      pneumovirus subfamily within the paramyxovirus family. HMPV infection is
      prevalent worldwide and is associated with severe respiratory disease,
      particularly in infants. The HMPV fusion protein (F) amino acid sequence contains
      features characteristic of other paramyxovirus F proteins, including a putative
      cleavage site and potential N-linked glycosylation sites. Propagation of HMPV in
      cell culture requires exogenous trypsin, which cleaves the F protein, and HMPV,
      like several other pneumoviruses, is infectious in the absence of its attachment
      protein (G). However, little is known about HMPV F-promoted fusion, since the
      HMPV glycoproteins have yet to be analyzed separately from the virus. Using
      syncytium and luciferase reporter gene fusion assays, we determined the basic
      requirements for HMPV F protein-promoted fusion in transiently transfected cells.
      Our data indicate that proteolytic cleavage of the F protein is a stringent
      requirement for fusion and that the HMPV G protein does not significantly enhance
      fusion. Unexpectedly, we also found that fusion can be detected only when
      transfected cells are treated with trypsin and exposed to low pH, indicating that
      this viral fusion protein may function in a manner unique among the
      paramyxoviruses. We also analyzed the F protein cleavage site and three potential
      N-linked glycosylation sites by mutagenesis. Mutations in the cleavage site
      designed to facilitate endogenous cleavage did so with low efficiency, and our
      data suggest that all three N-glycosylation sites are utilized and that each
      affects cleavage and fusion to various degrees.

PMID- 16971453
TI  - Spatial organization of transcription by RNA polymerase III.
AB  - RNA polymerase III (pol III) transcribes many essential, small, noncoding RNAs,
      including the 5S rRNAs and tRNAs. While most pol III-transcribed genes are found
      scattered throughout the linear chromosome maps or in multiple linear clusters,
      there is increasing evidence that many of these genes prefer to be spatially
      clustered, often at or near the nucleolus. This association could create an
      environment that fosters the coregulation of transcription by pol III with
      transcription of the large ribosomal RNA repeats by RNA polymerase I (pol I)
      within the nucleolus. Given the high number of pol III-transcribed genes in all
      eukaryotic genomes, the spatial organization of these genes is likely to affect a
      large portion of the other genes in a genome. In this Survey and Summary we
      analyze the reports regarding the spatial organization of pol III genes and
      address the potential influence of this organization on transcriptional
      regulation.

PMID- 16971454
TI  - Amino acid residues critical for RNA-binding in the N-terminal domain of the
      nucleocapsid protein are essential determinants for the infectivity of
      coronavirus in cultured cells.
AB  - The N-terminal domain of the coronavirus nucleocapsid (N) protein adopts a fold
      resembling a right hand with a flexible, positively charged beta-hairpin and a
      hydrophobic palm. This domain was shown to interact with the genomic RNA for
      coronavirus infectious bronchitis virus (IBV) and severe acute respiratory
      syndrome coronavirus (SARS-CoV). Based on its 3D structure, we used site-directed
      mutagenesis to identify residues essential for the RNA-binding activity of the
      IBV N protein and viral infectivity. Alanine substitution of either Arg-76 or Tyr
      94 in the N-terminal domain of IBV N protein led to a significant decrease in its
      RNA-binding activity and a total loss of the infectivity of the viral RNA to Vero
      cells. In contrast, mutation of amino acid Gln-74 to an alanine, which does not
      affect the binding activity of the N-terminal domain, showed minimal, if any,
      detrimental effect on the infectivity of IBV. This study thus identifies residues
      critical for RNA binding on the nucleocapsid surface, and presents biochemical
      and genetic evidence that directly links the RNA binding capacity of the
      coronavirus N protein to the viral infectivity in cultured cells. This
      information would be useful in development of preventive and treatment approaches
      against coronavirus infection.

PMID- 16971455
TI  - Effects of Dicer and Argonaute down-regulation on mRNA levels in human HEK293
      cells.
AB  - RNA interference and the microRNA (miRNA) pathway can induce sequence-specific
      mRNA degradation and/or translational repression. The human genome encodes
      hundreds of miRNAs that can post-transcriptionally repress thousands of genes.
      Using reporter constructs, we observed that degradation of mRNAs bearing sites
      imperfectly complementary to the endogenous let-7 miRNA is considerably stronger
      in human HEK293 than HeLa cells. The degradation did not result from the Ago2
      mediated endonucleolytic cleavage but it was Dicer- and Ago2-dependent. We used
      this feature of HEK293 to address the size of a pool of transcripts regulated by
      RNA silencing in a single cell type. We generated HEK293 cell lines depleted of
      Dicer or individual Ago proteins. The cell lines were used for microarray
      analyses to obtain a comprehensive picture of RNA silencing. The 3'-untranslated
      region sequences of a few hundred transcripts that were commonly up-regulated
      upon Ago2 and Dicer knock-downs showed a significant enrichment of putative miRNA
      binding sites. The up-regulation upon Ago2 and Dicer knock-downs was moderate and
      we found no evidence, at the mRNA level, for activation of silenced genes. Taken
      together, our data suggest that, independent of the effect on translation, miRNAs
      affect levels of a few hundred mRNAs in HEK293 cells.

PMID- 16971456
TI  - Homing endonuclease I-CreI derivatives with novel DNA target specificities.
AB  - Homing endonucleases are highly specific enzymes, capable of recognizing and
      cleaving unique DNA sequences in complex genomes. Since such DNA cleavage events
      can result in targeted allele-inactivation and/or allele-replacement in vivo, the
      ability to engineer homing endonucleases matched to specific DNA sequences of
      interest would enable powerful and precise genome manipulations. We have taken a
      step-wise genetic approach in analyzing individual homing endonuclease I-CreI
      protein/DNA contacts, and describe here novel interactions at four distinct
      target site positions. Crystal structures of two mutant endonucleases reveal the
      molecular interactions responsible for their altered DNA target specificities. We
      also combine novel contacts to create an endonuclease with the predicted target
      specificity. These studies provide important insights into engineering homing
      endonucleases with novel target specificities, as well as into the evolution of
      DNA recognition by this fascinating family of proteins.

PMID- 16971457
TI  - A spreadable, non-integrative and high copy number shuttle vector for Sulfolobus
      solfataricus based on the genetic element pSSVx from Sulfolobus islandicus.
AB  - The pSSVx genetic element from Sulfolobus islandicus REY15/4 is a hybrid between
      a plasmid and a fusellovirus, able to be maintained in non-integrative form and
      to spread when the helper SSV2 virus is present in the cells. In this work, the
      satellite virus was engineered to obtain an Escherichia coli-Sulfolobus
      solfataricus shuttle vector for gene transfer and expression in S.solfataricus by
      fusing site-specifically the pSSVx chromosome with an E.coli plasmid replicon and
      the ampicillin resistance gene. The pSSVx-based vector was proven functional like
      the parental virus, namely it was able to spread efficiently through infected
      S.solfataricus cells. Moreover, the hybrid plasmid stably transformed
      S.solfataricus and propagated with no rearrangement, recombination or integration
      into the host chromosome. The high copy number of the artificial genetic element
      was found comparable with that calculated for the wild-type pSSVx in the new host
      cells, with no need of genetic markers for vector maintenance in the cells and
      for transfomant enrichment. The newly constructed vector was also shown to be an
      efficient cloning vehicle for the expression of passenger genes in
      S.solfataricus. In fact, a derivative plasmid carrying an expression cassette of
      the lacS gene encoding the beta-glycosidase from S.solfataricus under the control
      of the Sulfolobus chaperonine (thermosome tf55) heat shock promoter was also able
      to drive the expression of a functional enzyme. Complementation of the beta
      galactosidase deficiency in a deletion mutant strain of S.solfataricus
      demonstrated that lacS gene was an efficient marker for selection of single
      transformants on solid minimal lactose medium.

PMID- 16971458
TI  - Identification of a plastid response element that acts as an enhancer within the
      Chlamydomonas HSP70A promoter.
AB  - Chloroplast-derived signals control a subset of nuclear genes in higher plants
      and eukaryotic algae. Among the types of signals identified are intermediates of
      chlorophyll biosynthesis such as Mg-protoporphyrin IX (MgProto). In Chlamydomonas
      reinhardtii, it was suggested that this tetrapyrrole mediates the light induction
      of chaperone gene HSP70A. Here we have analyzed cis elements involved in the
      regulation of HSP70A by MgProto and light. We identified two promoters and
      between their transcription start sites two regulatory regions that each may
      confer inducibility by MgProto and light to both HSP70A promoters. These
      regulatory regions, when cloned in front of basal non-light inducible
      heterologous promoters, conferred inducibility by MgProto and light. The
      orientation and distance independent function of these cis-regulatory sequences
      qualifies them as enhancers that mediate the response of nuclear genes to a
      chloroplast signal. Mutational analysis of one of these regulatory regions and an
      alignment with promoters of other MgProto-inducible genes revealed the sequence
      motif (G/C)CGA(C/T)N(A/G)N15 (T/C/A)(A/T/G) which, as shown for HSP70A, may
      confer MgProto responsiveness. This cis-acting sequence element is employed for
      induction of HSP70A by both MgProto and light, lending support to the model that
      light induction of this gene is mediated via MgProto.

PMID- 16971459
TI  - A simple DNA stretching method for fluorescence imaging of single DNA molecules.
AB  - Stretching or aligning DNA molecules onto a surface by means of molecular combing
      techniques is one of the critical steps in single DNA molecule analysis. However,
      many of the current studies have focused on lambda-DNA, or other large DNA
      molecules. There are very few studies on stretching methodologies for DNA
      molecules generated via PCR (typically smaller than 20 kb). Here we describe a
      simple method of stretching DNA molecules up to 18 kb in size on a modified glass
      surface. The very low background fluorescence allows efficient detection of
      single fluorescent dye labels incorporated into the stretched DNA molecules.

PMID- 16971460
TI  - Homology modeling using parametric alignment ensemble generation with consensus
      and energy-based model selection.
AB  - The accuracy of a homology model based on the structure of a distant relative or
      other topologically equivalent protein is primarily limited by the quality of the
      alignment. Here we describe a systematic approach for sequence-to-structure
      alignment, called 'K*Sync', in which alignments are generated by dynamic
      programming using a scoring function that combines information on many protein
      features, including a novel measure of how obligate a sequence region is to the
      protein fold. By systematically varying the weights on the different features
      that contribute to the alignment score, we generate very large ensembles of
      diverse alignments, each optimal under a particular constellation of weights. We
      investigate a variety of approaches to select the best models from the ensemble,
      including consensus of the alignments, a hydrophobic burial measure, low- and
      high-resolution energy functions, and combinations of these evaluation methods.
      The effect on model quality and selection resulting from loop modeling and
      backbone optimization is also studied. The performance of the method on a
      benchmark set is reported and shows the approach to be effective at both
      generating and selecting accurate alignments. The method serves as the foundation
      of the homology modeling module in the Robetta server.

PMID- 16971461
TI  - Zfp206 regulates ES cell gene expression and differentiation.
AB  - Understanding transcriptional regulation in early developmental stages is
      fundamental to understanding mammalian development and embryonic stem (ES) cell
      properties. Expression surveys suggest that the putative SCAN-Zinc finger
      transcription factor Zfp206 is expressed specifically in ES cells [Zhang,W.,
      Morris,Q.D., Chang,R., Shai,O., Bakowski,M.A., Mitsakakis,N., Mohammad,N.,
      Robinson,M.D., Zirngibl,R., Somogyi,E. et al., (2004) J. Biol., 3, 21;
      Brandenberger,R., Wei,H., Zhang,S., Lei,S., Murage,J., Fisk,G.J., Li,Y., Xu,C.,
      Fang,R., Guegler,K. et al., (2004) Nat. Biotechnol., 22, 707-716]. Here, we
      confirm this observation, and we show that ZFP206 expression decreases rapidly
      upon differentiation of cultured mouse ES cells, and during development of mouse
      embryos. We find that there are at least six isoforms of the ZFP206 transcript,
      the longest being predominant. Overexpression and depletion experiments show that
      Zfp206 promotes formation of undifferentiated ES cell clones, and positively
      regulates abundance of a very small set of transcripts whose expression is also
      specific to ES cells and the two- to four-cell stages of preimplantation embryos.
      This set includes members of the Zscan4, Thoc4, Tcstv1 and eIF-1A gene families,
      none of which have been functionally characterized in vivo but whose members
      include apparent transcription factors, RNA-binding proteins and translation
      factors. Together, these data indicate that Zfp206 is a regulator of ES cell
      differentiation that controls a set of genes expressed very early in development,
      most of which themselves appear to be regulators.

PMID- 16971462
TI  - CK2-mediated stimulation of Pol I transcription by stabilization of UBF-SL1
      interaction.
AB  - High levels of rRNA synthesis by RNA polymerase I are important for cell growth
      and proliferation. In vitro studies have indicated that the formation of a stable
      complex between the HMG box factor [Upstream binding factor (UBF)] and SL1 at the
      rRNA gene promoter is necessary to direct multiple rounds of Pol I transcription
      initiation. The recruitment of SL1 to the promoter occurs through protein
      interactions with UBF and is regulated by phosphorylation of UBF. Here we show
      that the protein kinase CK2 co-immunoprecipitates with the Pol I complex and is
      associated with the rRNA gene promoter. Inhibition of CK2 kinase activity reduces
      Pol I transcription in cultured cells and in vitro. Significantly, CK2 regulates
      the interaction between UBF and SL1 by counteracting the inhibitory effect of HMG
      boxes five and six through the phosphorylation of specific serines located at the
      C-terminus of UBF. Transcription reactions with immobilized templates indicate
      that phosphorylation of CK2 phosphoacceptor sites in the C-terminal domain of UBF
      is important for promoting multiple rounds of Pol I transcription. These data
      demonstrate that CK2 is recruited to the rRNA gene promoter and directly
      regulates Pol I transcription re-initiation by stabilizing the association
      between UBF and SL1.

PMID- 16971463
TI  - Biochemical analysis of the substrate specificity and sequence preference of
      endonuclease IV from bacteriophage T4, a dC-specific endonuclease implicated in
      restriction of dC-substituted T4 DNA synthesis.
AB  - Endonuclease IV encoded by denB of bacteriophage T4 is implicated in restriction
      of deoxycytidine (dC)-containing DNA in the host Escherichia coli. The enzyme was
      synthesized with the use of a wheat germ cell-free protein synthesis system,
      given a lethal effect of its expression in E.coli cells, and was purified to
      homogeneity. The purified enzyme showed high activity with single-stranded (ss)
      DNA and denatured dC-substituted T4 genomic double-stranded (ds) DNA but
      exhibited no activity with dsDNA, ssRNA or denatured T4 genomic dsDNA containing
      glucosylated deoxyhydroxymethylcytidine. Characterization of Endo IV activity
      revealed that the enzyme catalyzed specific endonucleolytic cleavage of the 5'
      phosphodiester bond of dC in ssDNA with an efficiency markedly dependent on the
      surrounding nucleotide sequence. The enzyme preferentially targeted 5'-dTdCdA-3'
      but tolerated various combinations of individual nucleotides flanking this
      trinucleotide sequence. These results suggest that Endo IV preferentially
      recognizes short nucleotide sequences containing 5'-dTdCdA-3', which likely
      accounts for the limited digestion of ssDNA by the enzyme and may be responsible
      in part for the indispensability of a deficiency in denB for stable synthesis of
      dC-substituted T4 genomic DNA.

PMID- 16971464
TI  - The fidelity of DNA synthesis by yeast DNA polymerase zeta alone and with
      accessory proteins.
AB  - DNA polymerase zeta (pol zeta) participates in several DNA transactions in
      eukaryotic cells that increase spontaneous and damage-induced mutagenesis. To
      better understand this central role in mutagenesis in vivo, here we report the
      fidelity of DNA synthesis in vitro by yeast pol zeta alone and with RFC, PCNA and
      RPA. Overall, the accessory proteins have little effect on the fidelity of pol
      zeta. Pol zeta is relatively accurate for single base insertion/deletion errors.
      However, the average base substitution fidelity of pol zeta is substantially
      lower than that of homologous B family pols alpha, delta and epsilon. Pol zeta is
      particularly error prone for substitutions in specific sequence contexts and
      generates multiple single base errors clustered in short patches at a rate that
      is unprecedented in comparison with other polymerases. The unique error
      specificity of pol zeta in vitro is consistent with Pol zeta-dependent mutagenic
      specificity reported in vivo. This fact, combined with the high rate of single
      base substitution errors and complex mutations observed here, indicates that pol
      zeta contributes to mutagenesis in vivo not only by extending mismatches made by
      other polymerases, but also by directly generating its own mismatches and then
      extending them.

PMID- 16971465
TI  - Lipids in dendritic cell biology: messengers, effectors, and antigens.
AB  - Dendritic cells (DC) are the most professional APC, which induce and coordinate
      immune responses. The principal task of DC is T cell activation, although DC also
      interact with and regulate other cell types. The present review serves to
      illustrate the increasing evidence that lipids play an important role in DC
      biology. In addition to being fuel stores and structural components of cellular
      membranes such as in other cell types, lipids act as second messengers and as
      effectors throughout all steps of DC differentiation and regulate important DC
      functions. The recent finding that DC synthesize lipid antigens in response to
      bacterial stimulation and induce antibacterial, CD1-restricted T cells through
      antigenic mimicry further emphasizes the important role of lipids and DC at the
      blurring boundaries of innate and adaptive immunity.

PMID- 16971466
TI  - IFN-gamma-activated monocytes weakly produce HIV-1 but induce the recruitment of
      HIV-sensitive T cells and enhance the viral production by these recruited T
      cells.
AB  - The ability of macrophages to adapt to changing cytokine environments results in
      the dominance of a particular functional phenotype of macrophages, which would
      play a significant role in HIV pathogenesis. In comparison with untreated
      macrophages (M0), we examined the role of macrophages derived from IFN-gamma
      activated monocytes (M1) in the HIV spread. We show that M0 and M1 bind with the
      same efficiency HIV-1 with a predominant role of C-type lectins in the R5-HIV
      attachment and of the heparan sulfate proteoglycans in the X4-HIV attachment.
      Despite similar levels of R5- and X4-HIV DNA, M1 replicates and weakly transmits
      the virus to activated T cells by releasing CXCR4- and CCR5-interacting
      chemokines. The blockade of dendritic cell-specific ICAM-3-grabbing nonintegrin
      expressed on M1 by mAb does not interfere with the viral transfer. Uninfected M1
      recruits HIV-sensitive T cells efficiently and releases soluble factors,
      enhancing the viral production by these recruited cells. This study highlights
      the role of IFN-gamma to induce a population of macrophages that archive HIV-1
      within a latent stage and cause the persistence of the virus by favoring the
      recruitment of T cells or enhancing the viral replication in infected CD4(+) T
      cells.

PMID- 16971467
TI  - Zinc-finger genes Fez and Fez-like function in the establishment of diencephalon
      subdivisions.
AB  - Fez and Fez-like (Fezl) are zinc-finger genes that encode transcriptional
      repressors expressed in overlapping domains of the forebrain. By generating
      Fez;Fezl-deficient mice we found that a redundant function of Fez and Fezl is
      required for the formation of diencephalon subdivisions. The caudal forebrain can
      be divided into three transverse subdivisions: prethalamus (also called ventral
      thalamus), thalamus (dorsal thalamus) and pretectum. Fez;Fezl-deficient mice
      showed a complete loss of prethalamus and a strong reduction of the thalamus at
      late gestation periods. Genetic marker analyses revealed that during early
      diencephalon patterning in Fez;Fezl-deficient mice, the rostral diencephalon
      (prospective prethalamus) did not form and the caudal diencephalon (prospective
      thalamus and pretectum) expanded rostrally. Fez;Fezl-deficient mice also
      displayed defects in the formation of the zona limitans intrathalamica (ZLI),
      which is located on the boundary between the prethalamus and thalamus. Fez and
      Fezl are expressed in the region rostral to the rostral limit of Irx1 expression,
      which marks the prospective position of the ZLI. Transgene-mediated misexpression
      of Fezl or Fez caudal to the ZLI repressed the caudal diencephalon fate and
      affected the formation of the Shh-expressing ZLI. These data indicate that Fez
      and Fezl repress the caudal diencephalon fate in the rostral diencephalon, and
      ZLI formation probably depends on Fez/Fezl-mediated formation of diencephalon
      subdivisions.

PMID- 16971468
TI  - Semaphorin 3d promotes cell proliferation and neural crest cell development
      downstream of TCF in the zebrafish hindbrain.
AB  - Neural crest cells (NCCs) are pluripotent migratory cells that are crucial to the
      development of the peripheral nervous system, pigment cells and craniofacial
      cartilage and bone. NCCs are specified within the dorsal ectoderm and undergo an
      epithelial to mesenchymal transition (EMT) in order to migrate to target
      destinations where they differentiate. Here we report a role for a member of the
      semaphorin family of cell guidance molecules in NCC development. Morpholino
      mediated knockdown of Sema3d inhibits the proliferation of hindbrain
      neuroepithelial cells. In addition, Sema3d knockdown reduces markers of migratory
      NCCs and disrupts NCC-derived tissues. Similarly, expression of a dominant
      repressor form of TCF (DeltaTCF) reduces hindbrain cell proliferation and leads
      to a disruption of migratory NCC markers. Moreover, expression of DeltaTCF
      downregulates sema3d RNA expression. Finally, Sema3d overexpression rescues
      reduced proliferation caused by DeltaTCF expression, suggesting that Sema3d lies
      downstream of Wnt/TCF signaling in the molecular pathway thought to control cell
      cycle in NCC precursors.

PMID- 16971469
TI  - Translational control of regA, a key gene controlling cell differentiation in
      Volvox carteri.
AB  - The complete division of labour between the reproductive and somatic cells of the
      green alga Volvox carteri is controlled by three types of genes. One of these is
      the regA gene, which controls terminal differentiation of the somatic cells.
      Here, we examined translational control elements located in the 5' UTR of regA,
      particularly the eight upstream start codons (AUGs) that have to be bypassed by
      the translation machinery before regA can be translated. The results of our
      systematic mutational, structural and functional analysis of the 5' UTR led us to
      conclude that a ribosome-shunting mechanism--rather than leaky scanning,
      ribosomal reinitiation, or internal ribosome entry site (IRES)-mediated
      initiation--controls the translation of regA mRNA. This mechanism, which involves
      dissociation of the 40S initiation complex from the message, followed by
      reattachment downstream, in order to bypass a secondary structure block in the
      mRNA, was validated by deleting the predicted ;landing site' (which prevented
      regA expression) and inserting a stable 64 nucleotide hairpin just upstream of
      this site (which did not prevent regA expression). We believe that this is the
      first report suggesting that translation of an mRNA in a green eukaryote is
      controlled by ribosome shunting.

PMID- 16971470
TI  - At the next stop sign turn right: the metalloprotease Tolloid-related 1 controls
      defasciculation of motor axons in Drosophila.
AB  - Navigation of motoneuronal growth cones toward the somatic musculature in
      Drosophila serves as a model system to unravel the molecular mechanisms of axon
      guidance and target selection. In a large-scale mutagenesis screen, we identified
      piranha, a motor axon guidance mutant that shows strong defects in the
      neuromuscular connectivity pattern. In piranha mutant embryos, permanent
      defasciculation errors occur at specific choice points in all motor pathways.
      Positional cloning of piranha revealed point mutations in tolloid-related 1
      (tlr1), an evolutionarily conserved gene encoding a secreted metalloprotease.
      Ectopic expression of Tlr1 in several tissues of piranha mutants, including
      hemocytes, completely restores the wild-type innervation pattern, indicating that
      Tlr1 functions cell non-autonomously. We further show that loss-of-function
      mutants of related metalloproteases do not have motor axon guidance defects and
      that the respective proteins cannot functionally replace Tlr1. tlr1, however,
      interacts with sidestep, a muscle-derived attractant. Double mutant larvae of
      tlr1 and sidestep show an additive phenotype and lack almost all neuromuscular
      junctions on ventral muscles, suggesting that Tlr1 functions together with
      Sidestep in the defasciculation process.

PMID- 16971471
TI  - A caudal mRNA gradient controls posterior development in the wasp Nasonia.
AB  - One of the earliest steps of embryonic development is the establishment of
      polarity along the anteroposterior axis. Extensive studies of Drosophila
      embryonic development have elucidated mechanisms for establishing polarity, while
      studies with other model systems have found that many of these molecular
      components are conserved through evolution. One exception is Bicoid, the master
      organizer of anterior development in Drosophila and higher dipterans, which is
      not conserved. Thus, the study of anteroposterior patterning in insects that lack
      Bicoid can provide insight into the evolution of the diversity of body plan
      patterning networks. To this end, we have established the long germ parasitic
      wasp Nasonia vitripennis as a model for comparative studies with Drosophila. Here
      we report that, in Nasonia, a gradient of localized caudal mRNA directs posterior
      patterning, whereas, in Drosophila, the gradient of maternal Caudal protein is
      established through translational repression by Bicoid of homogeneous caudal
      mRNA. Loss of caudal function in Nasonia results in severe segmentation defects.
      We show that Nasonia caudal is an activator of gap gene expression that acts far
      towards the anterior of the embryo, placing it atop a cascade of early
      patterning. By contrast, activation of gap genes in flies relies on redundant
      functions of Bicoid and Caudal, leading to a lack of dramatic action on gap gene
      expression: caudal instead plays a limited role as an activator of pair-rule gene
      expression. These studies, together with studies in short germ insects, suggest
      that caudal is an ancestral master organizer of patterning, and that its role has
      been reduced in higher dipterans such as Drosophila.

PMID- 16971472
TI  - The role of Tudor domains in germline development and polar granule architecture.
AB  - Tudor domains are found in many organisms and have been implicated in protein
      protein interactions in which methylated protein substrates bind to these
      domains. Here, we present evidence for the involvement of specific Tudor domains
      in germline development. Drosophila Tudor, the founder of the Tudor domain
      family, contains 11 Tudor domains and is a component of polar granules and nuage,
      electron-dense organelles characteristic of the germline in many organisms,
      including mammals. In this study, we investigated whether the 11 Tudor domains
      fulfil specific functions for polar granule assembly, germ cell formation and
      abdomen formation. We find that even a small number of non-overlapping Tudor
      domains or a substantial reduction in overall Tudor protein is sufficient for
      abdomen development. In stark contrast, we find a requirement for specific Tudor
      domains in germ cell formation, Tudor localization and polar granule
      architecture. Combining genetic analysis with structural modeling of specific
      Tudor domains, we propose that these domains serve as ;docking platforms' for
      polar granule assembly.

PMID- 16971473
TI  - The gammaTuRC components Grip75 and Grip128 have an essential microtubule
      anchoring function in the Drosophila germline.
AB  - The gamma-tubulin ring complex (gammaTuRC) forms an essential template for
      microtubule nucleation in animal cells. The molecular composition of the
      gammaTuRC has been described; however, the functions of the subunits proposed to
      form the cap structure remain to be characterized in vivo. In Drosophila, the
      core components of the gammaTuRC are essential for mitosis, whereas the cap
      component Grip75 is not required for viability but functions in bicoid RNA
      localization during oogenesis. The other cap components have not been analyzed in
      vivo. We report the functional characterization of the cap components Grip128 and
      Grip75. Animals with mutations in Dgrip128 or Dgrip75 are viable, but both males
      and females are sterile. Both proteins are required for the formation of distinct
      sets of microtubules, which facilitate bicoid RNA localization during oogenesis,
      the formation of the central microtubule aster connecting the meiosis II spindles
      in oocytes and cytokinesis in male meiosis. Grip75 and Grip128 anchor the axoneme
      at the nucleus during sperm elongation. We propose that Grip75 and Grip128 are
      required to tether microtubules at specific microtubule-organizing centers,
      instead of being required for general microtubule nucleation. The gammaTuRC cap
      structure may be essential only for non-centrosome-based microtubule functions.

PMID- 16971474
TI  - Interaction between Polo and BicD proteins links oocyte determination and meiosis
      control in Drosophila.
AB  - Meiosis is a specialized cell cycle limited to the gametes in Metazoa. In
      Drosophila, oocyte determination and meiosis control are interdependent
      processes, and BicD appears to play a key role in both. However, the exact
      mechanism of how BicD-dependent polarized transport could influence meiosis and
      vice versa remains an open question. In this article, we report that the cell
      cycle regulatory kinase Polo binds to BicD protein during oogenesis. Polo is
      expressed in all cells during cyst formation before specifically localizing to
      the oocyte. This is the earliest known example of asymmetric localization of a
      cell-cycle regulator in this process. This localization is dependent on BicD and
      the Dynein complex. Loss- and gain-of-function experiments showed that Polo has
      two independent functions. On the one hand, it acts as a trigger for meiosis. On
      the other hand, it is independently required, in a cell-autonomous manner, for
      the activation of BicD-dependent transport. Moreover, we show that Polo
      overexpression can rescue a hypomorphic mutation of BicD by restoring its
      localization and its function, suggesting that the requirement for Polo in
      polarized transport acts through regulation of BicD. Taken together, our data
      indicate the existence of a positive feedback loop between BicD and Polo, and we
      propose that this loop represents a functional link between oocyte specification
      and the control of meiosis.

PMID- 16971475
TI  - ASYMMETRIC LEAVES1 and auxin activities converge to repress BREVIPEDICELLUS
      expression and promote leaf development in Arabidopsis.
AB  - Leaf development in higher plants requires the specification of leaf initials at
      the flanks of a pluripotent structure termed the shoot apical meristem. In
      Arabidopsis, this process is facilitated by negative interactions between class I
      KNOTTED1-like homeobox (KNOX) and ASYMMETRIC LEAVES1 (AS1) transcription factors,
      such that KNOX proteins are confined to the meristem and AS1 to leaf initials.
      Sites of leaf inception are also defined by local accumulation of the hormone
      auxin; however, it is unknown how auxin and AS1 activities are integrated to
      control leaf development. Here, we show that auxin and AS1 pathways converge to
      repress expression of the KNOX gene BREVIPEDICELLUS (BP) and thus promote leaf
      fate. We also demonstrate that regulated auxin gradients control leaf shape in a
      KNOX-independent fashion and that inappropriate KNOX activity in leaves perturbs
      these gradients, hence altering leaf shape. We propose that regulatory
      interactions between auxin, AS1 and KNOX activities may both direct leaf
      initiation and sculpt leaf form.

PMID- 16971476
TI  - A dynamic expression survey identifies transcription factors relevant in mouse
      digestive tract development.
AB  - Tissue-restricted transcription factors (TFs), which confer specialized cellular
      properties, are usually identified through sequence homology or cis-element
      analysis of lineage-specific genes; conventional modes of mRNA profiling often
      fail to report non-abundant TF transcripts. We evaluated the dynamic expression
      during mouse gut organogenesis of 1381 transcripts, covering nearly every known
      and predicted TF, and documented the expression of approximately 1000 TF genes in
      gastrointestinal development. Despite distinctive structures and functions, the
      stomach and intestine exhibit limited differences in TF genes. Among
      differentially expressed transcripts, a few are virtually restricted to the
      digestive tract, including Nr2e3, previously regarded as a photoreceptor-specific
      product. TFs that are enriched in digestive organs commonly serve essential
      tissue-specific functions, hence justifying a search for other tissue-restricted
      TFs. Computational data mining and experimental investigation focused interest on
      a novel homeobox TF, Isx, which appears selectively in gut epithelium and mirrors
      expression of the intestinal TF Cdx2. Isx-deficient mice carry a specific defect
      in intestinal gene expression: dysregulation of the high density lipoprotein
      (HDL) receptor and cholesterol transporter scavenger receptor class B, type I
      (Scarb1). Thus, integration of developmental gene expression with biological
      assessment, as described here for TFs, represents a powerful tool to investigate
      control of tissue differentiation.

PMID- 16971477
TI  - Systems biology of AGC kinases in fungi.
AB  - Sch9 appears to be the Saccharomyces cerevisiae homolog of protein kinase B and
      is involved in the control of numerous nutrient-sensitive processes, including
      regulation of cell size, cell cycle progression, and stress resistance. Sch9 has
      also been implicated in the regulation of replicative and chronological life
      span. Systematic comparison of the phenotypes of sch9 and other AGC kinase
      mutants in fungal species with their counterparts in model eukaryotic organisms
      provides insight into the functions of AGC kinases. The availability of data from
      global studies of protein-protein interactions now makes it possible to predict
      and validate functional connections between Sch9, its putative substrates, and
      other proteins. This review highlights several emerging paradigms of AGC kinase
      signaling that are relevant for growth, development, and aging.

PMID- 16971478
TI  - Epidermolysis bullosa. II. Type VII collagen mutations and phenotype-genotype
      correlations in the dystrophic subtypes.
AB  - BACKGROUND: The dystrophic forms of epidermolysis bullosa (DEB), a group of
      heritable blistering disorders, show considerable phenotypic variability, and
      both autosomal dominant and autosomal recessive inheritance can be recognised.
      DEB is derived from mutations in the type VII collagen gene (COL7A1), encoding a
      large collagenous protein that is the predominant, if not exclusive, component of
      the anchoring fibrils at the dermal-epidermal junction. METHODS: The Dystrophic
      Epidermolysis Bullosa Research Association Molecular Diagnostics Laboratory
      (Philadelphia, Pennsylvania, USA), established in 1996, has analysed more than
      1000 families with different forms of epidermolysis bullosa, among them 332
      families with DEB. DNA specimens were subjected to mutation analysis by
      polymerase chain reaction (PCR) amplification of all 118 exons and flanking
      intronic sequences of COL7A1, followed either by heteroduplex scanning and
      sequencing of the PCR products demonstrating heteroduplexes or by direct
      nucleotide sequencing. RESULTS: 355 mutant alleles out of the anticipated 438
      (81.1%) were disclosed. Among these mutations, a total of 242 mutations were
      distinct and 138 were novel, previously unreported mutations. No evidence of
      mutations in any other gene was obtained. DISCUSSION: Examination of the mutation
      database suggested phenotype-genotype correlations, contributing to the improved
      subclassification of DEB with prognostic implications. The mutation information
      also forms the basis for accurate genetic counselling and prenatal diagnosis in
      families at risk for recurrence.

PMID- 16971479
TI  - Ultra-high resolution array painting facilitates breakpoint sequencing.
AB  - OBJECTIVE: To describe a considerably advanced method of array painting, which
      allows the rapid, ultra-high resolution mapping of translocation breakpoints such
      that rearrangement junction fragments can be amplified directly and sequenced.
      METHOD: Ultra-high resolution array painting involves the hybridisation of probes
      generated by the amplification of small numbers of flow-sorted derivative
      chromosomes to oligonucleotide arrays designed to tile breakpoint regions at
      extremely high resolution. RESULTS AND DISCUSSION: How ultra-high resolution
      array painting of four balanced translocation cases rapidly and efficiently maps
      breakpoints to a point where junction fragments can be amplified easily and
      sequenced is demonstrated. With this new development, breakpoints can be mapped
      using just two array experiments: the first using whole-genome array painting to
      tiling resolution large insert clone arrays, the second using ultra-high
      resolution oligonucleotide arrays targeted to the breakpoint regions. In this
      way, breakpoints can be mapped and then sequenced in a few weeks.

PMID- 16971480
TI  - Screening of calpain-3 autolytic activity in LGMD muscle: a functional map of
      CAPN3 gene mutations.
AB  - BACKGROUND: The diagnosis of calpainopathy is obtained by identifying calpain-3
      protein deficiency or CAPN3 gene mutations. However, in many patients with limb
      girdle muscular dystrophy type 2A (LGMD2A), the calpain-3 protein quantity is
      normal because loss-of-function mutations cause its enzymatic inactivation. The
      identification of such patients is difficult unless a functional test suggests
      pursuing a search for mutations. MATERIALS AND METHODS: A functional in vitro
      assay, which was able to test calpain-3 autolytic function, was used to screen a
      large series of muscle biopsy specimens from patients with unclassified
      LGMD/hyperCKaemia who have previously shown normal calpain-3 protein quantity.
      RESULTS: Of 148 muscle biopsy specimens tested,17 samples (11%) had lost normal
      autolytic function. CAPN3 gene mutations were identified in 15 of 17 patients
      (88%), who account for about 20% of the total patients with LGMD2A diagnosed in
      our series. CONCLUSIONS: The loss of calpain-3 autolytic activity is highly
      predictive of primary calpainopathy, and the use of this test as part of
      calpainopathy diagnosis would improve the rate of disease detection markedly.
      This study provides the first evidence of the pathogenetic effect of specific
      CAPN3 gene mutations on the corresponding protein function in LGMD2A muscle and
      offers new insights into the structural-functional relationship of the gene and
      protein regions that are crucial for the autolytic activity of calpain-3.

PMID- 16971481
TI  - An atypical deletion of the Williams-Beuren syndrome interval implicates genes
      associated with defective visuospatial processing and autism.
AB  - BACKGROUND: During a genetic study of autism, a female child who met diagnostic
      criteria for autism spectrum disorder, but also exhibited the cognitive
      behavioural profile (CBP) associated with Williams-Beuren syndrome (WBS) was
      examined. The WBS CBP includes impaired visuospatial ability, an overly friendly
      personality, excessive non-social anxiety and language delay. METHODS: Using
      array-based comparative genomic hybridisation (aCGH), a deletion corresponding to
      BAC RP11-89A20 in the distal end of the WBS deletion interval was detected.
      Hemizygosity was confirmed using fluorescence in situ hybridisation and fine
      mapping was performed by measuring the copy number of genomic DNA using
      quantitative polymerase chain reaction. RESULTS: The proximal breakpoint was
      mapped to intron 1 of GTF2IRD1 and the distal breakpoint lies 2.4-3.1 Mb towards
      the telomere. The subject was completely hemizygous for GTF2I, commonly deleted
      in carriers of the classic approximately 1.5 Mb WBS deletion, and GTF2IRD2,
      deleted in carriers of the rare approximately 1.84 Mb WBS deletion. CONCLUSION:
      Hemizygosity of the GTF2 family of transcription factors is sufficient to produce
      many aspects of the WBS CBP, and particularly implicate the GTF2 transcription
      factors in the visuospatial construction deficit. Symptoms of autism in this case
      may be due to deletion of additional genes outside the typical WBS interval or
      remote effects on gene expression at other loci.

PMID- 16971482
TI  - Genetic and epigenetic defects at the 6q24 imprinted locus in a cohort of 13
      patients with transient neonatal diabetes: new hypothesis raised by the finding
      of a unique case with hemizygotic deletion in the critical region.
AB  - BACKGROUND: Transient neonatal diabetes (TND) is a rare form of diabetes usually
      present in the first few days after birth that resolves within 1 year but that
      has a tendency to recur later in life. It can be associated with chromosome 6
      paternal uniparental disomy (UPD), paternal duplications or loss of maternal
      methylation at the 6q24 imprinted locus. OBJECTIVE: To report on a cohort of 13
      sporadic TND cases, including five with birth defects (congenital abnormalities
      of heart, brain and bone) and eight without. RESULTS: The hallmarks of diabetes
      were similar in patients with or without 6q24 defects. The chromosome 6
      abnormalities in our patients (n = 13) included 2 of 13 (approximately 15.4%)
      cases of paternal UPD6, 2 of 11 (approximately 18%) cases of complete and 3 of 11
      (approximately 27%) cases of partial loss of the maternal methylation signature
      upstream of ZAC1-HYMAI imprinted genes in non-UPD cases, and 1 of 13
      (approximately 7.7%) cases of hemizygotic deletion. CONCLUSION: The deletion was
      found in a patient with severe congenital abnormalities. This genetic lesion was
      not reported previously. The hypothesis of an effect on regulatory elements
      critical for imprinting and tissue-specific gene expression in early development
      by the deletion is raised. The data presented here may contribute to the
      diagnosis and the understanding of imprinting in the region.

PMID- 16971483
TI  - A therapeutic target for prostate cancer based on angiogenin-stimulated
      angiogenesis and cancer cell proliferation.
AB  - Human angiogenin is progressively up-regulated in the prostate epithelial cells
      during the development of prostate cancer from prostate intraepithelial neoplasia
      (PIN) to invasive adenocarcinoma. Mouse angiogenin is the most up-regulated gene
      in AKT-induced PIN in prostate-restricted AKT transgenic mice. These results
      prompted us to study the role that angiogenin plays in prostate cancer. Here, we
      report that, in addition to its well established role in mediating angiogenesis,
      angiogenin also directly stimulates prostate cancer cell proliferation.
      Angiogenin undergoes nuclear translocation in PC-3 human prostate cancer cells
      grown both in vitro and in mice. Thus, knocking down angiogenin expression in PC
      3 human prostate adenocarcinoma cells inhibits ribosomal RNA transcription, in
      vitro cell proliferation, colony formation in soft agar, and xenograft growth in
      athymic mice. Blockade of nuclear translocation of angiogenin by the
      aminoglycoside antibiotic neomycin inhibited PC-3 cell tumor growth in athymic
      mice and was accompanied by a decrease in both cancer cell proliferation and
      angiogenesis. These results suggest that angiogenin has a dual effect,
      angiogenesis and cancer cell proliferation, in prostate cancer and may serve as a
      molecular target for drug development. Blocking nuclear translocation of
      angiogenin could have a combined benefit of antiangiogenesis and chemotherapy in
      treating prostate cancer.

PMID- 16971484
TI  - Differential microarray analysis of Drosophila mushroom body transcripts using
      chemical ablation.
AB  - Mushroom bodies (MBs) are the centers for olfactory associative learning and
      elementary cognitive functions in the Drosophila brain. As a way to
      systematically elucidate genes preferentially expressed in MBs, we have analyzed
      genome-wide alterations in transcript profiles associated with MB ablation by
      hydroxyurea. We selected 100 genes based on microarray data and examined their
      expression patterns in the brain by in situ hybridization. Seventy genes were
      found to be expressed in the posterodorsal cortex, which harbors the MB cell
      bodies. These genes encode proteins of diverse functions, including
      transcription, signaling, cell adhesion, channels, and transporters. Moreover, we
      have examined developmental functions of 40 of the microarray-identified genes by
      transgenic RNA interference; 8 genes were found to cause mild-to-strong MB
      defects when suppressed with a MB-Gal4 driver. These results provide important
      information not only on the repertoire of genes that control MB development but
      also on the repertoire of neural factors that may have important physiological
      functions in MB plasticity.

PMID- 16971485
TI  - Codon-usage bias versus gene conversion in the evolution of yeast duplicate
      genes.
AB  - Many Saccharomyces cerevisiae duplicate genes that were derived from an ancient
      whole-genome duplication (WGD) unexpectedly show a small synonymous divergence
      (K(S)), a higher sequence similarity to each other than to orthologues in
      Saccharomyces bayanus, or slow evolution compared with the orthologue in
      Kluyveromyces waltii, a non-WGD species. This decelerated evolution was
      attributed to gene conversion between duplicates. Using approximately 300 WGD
      gene pairs in four species and their orthologues in non-WGD species, we show that
      codon-usage bias and protein-sequence conservation are two important causes for
      decelerated evolution of duplicate genes, whereas gene conversion is effective
      only in the presence of strong codon-usage bias or protein-sequence conservation.
      Furthermore, we find that change in mutation pattern or in tDNA copy number
      changed codon-usage bias and increased the K(S) distance between K. waltii and S.
      cerevisiae. Intriguingly, some proteins showed fast evolution before the
      radiation of WGD species but little or no sequence divergence between orthologues
      and paralogues thereafter, indicating that functional conservation after the
      radiation may also be responsible for decelerated evolution in duplicates.

PMID- 16971486
TI  - Intracellular IL-1alpha-binding proteins contribute to biological functions of
      endogenous IL-1alpha in systemic sclerosis fibroblasts.
AB  - The aberrant production of precursor IL-1alpha (pre-IL-1alpha) in skin
      fibroblasts that are derived from systemic sclerosis (SSc) is associated with the
      induction of IL-6 and procollagen, which contributes to the fibrosis of SSc.
      However, little is understood about how intracellular pre-IL-1alpha regulates the
      expression of the other molecules in fibroblasts. We report here that pre-IL
      1alpha can form a complex with IL-1alpha-binding proteins that is translocated
      into the nuclei of fibroblasts. Immunoprecipitation that used anti-human IL
      1alpha Ab and (35)S-labeled nuclear extracts of fibroblasts showed three specific
      bands (approximately equal to 31, 35, and 65 kDa). The 31-kDa molecule was
      identified as pre-IL-1alpha, and the 35- and 65-kDa molecules might be pre-IL
      1alpha-binding proteins. A partial sequencing for the 10 aa from the N-terminals
      of the molecules showed 100% homology for HAX-1 (HS1-associated protein X-1) and
      IL-1 receptor type II (IL-1RII). Suppression of the genes of HAX-1 or IL-1RII
      induced the inhibitory effects of IL-1 signal transduction, including production
      of IL-6 and procollagen, by fibroblasts. In particular, pre-IL-1alpha was not
      translocated into the nucleus by an inhibition of HAX-1. These findings reveal
      that nuclear localization of pre-IL-1alpha depends on the binding to HAX-1 and
      that biological activities might be elicited by the binding to both HAX-1 and IL
      1RII in SSc fibroblasts.

PMID- 16971487
TI  - Activation of NF-kappaB by the intracellular expression of NF-kappaB-inducing
      kinase acts as a powerful vaccine adjuvant.
AB  - There is a pressing need for adjuvants that will enhance the effectiveness of
      genetic vaccines. This is particularly important in cancer and infectious disease
      such as HIV and malaria for which successful vaccines are desperately needed.
      Here, we describe an approach to enhance immunogenicity that involves the
      activation of NF-kappaB by the transgenic expression of an intracellular
      signaling molecule, NF-kappaB-inducing kinase (NIK). In vitro, NIK increases
      dendritic cell antigen presentation in allogeneic and antigen-specific T cell
      proliferation assays by potently activating NF-kappaB and consequently up
      regulating the expression of cytokines (TNF-alpha, IL-6, IL-12, IL-15, and IL
      18), chemokines [IL-8, RANTES (regulated on activation, normal T cell expressed
      and secreted), macrophage inflammatory protein-1alpha, monocyte chemoattractant
      protein-1, and monocyte chemoattractant protein-3], MHC antigen-presenting
      molecules (class I and II), and costimulatory molecules (CD80 and CD86). In vivo,
      NIK enhances immune responses against a vector-encoded antigen and shifts them
      toward a T helper 1 immune response with increased IgG2a levels, T cell
      proliferation, IFN-gamma production, and cytotoxic T lymphocyte responses more
      potently than complete Freund's adjuvant, a very efficacious T helper 1-inducing
      adjuvant. These findings define NIK, and possibly other inducers of NF-kappaB
      activation, as a potent adjuvant strategy that offers great potential for genetic
      vaccine development.

PMID- 16971488
TI  - Role of cocaine- and amphetamine-regulated transcript in estradiol-mediated
      neuroprotection.
AB  - Estrogen reduces brain injury after experimental cerebral ischemia in part
      through a genomic mechanism of action. Using DNA microarrays, we analyzed the
      genomic response of the brain to estradiol, and we identified a transcript,
      cocaine- and amphetamine-regulated transcript (CART), that is highly induced in
      the cerebral cortex by estradiol under ischemic conditions. Using in vitro and in
      vivo models of neural injury, we confirmed and characterized CART mRNA and
      protein up-regulation by estradiol in surviving neurons, and we demonstrated that
      i.v. administration of a rat CART peptide is protective against ischemic brain
      injury in vivo. We further demonstrated binding of cAMP response element (CRE)
      binding protein to a CART promoter CRE site in ischemic brain and rapid
      activation by CART of ERK in primary cultured cortical neurons. The findings
      suggest that CART is an important player in estrogen-mediated neuroprotection and
      a potential therapeutic agent for stroke and other neurodegenerative diseases.

PMID- 16971489
TI  - Lakes of liquid CO2 in the deep sea.

PMID- 16971490
TI  - Rapid effects of aldosterone on clonal human vascular smooth muscle cells.
AB  - It has been increasingly appreciated that aldosterone elicits acute vascular
      effects through nongenomic signaling pathways. Our previous studies demonstrated
      that aldosterone attenuated phenylephrine-mediated constriction in intact vessels
      [via phosphatidylinositol 3-kinase-dependent nitric oxide synthase activation]
      but enhanced vasoconstrictor responses in endothelium-denuded arteries. To
      determine the mechanism of this vasoconstrictor response, we assessed the effect
      of aldosterone on myosin light-chain phosphorylation and contraction in clonal
      adult human vascular smooth muscle cells. Acute aldosterone exposure mediated
      dose-dependent myosin light-chain phosphorylation, inhibited by spironolactone
      and phosphatidylinositol 3-kinase inhibition. These rapid effects of aldosterone
      were mimicked by estradiol and hydrocortisone and were also inhibitable by both
      spironolactone and eplerenone. In parallel to its effects on myosin light-chain
      phosphorylation, aldosterone mediated dose-dependent contraction responses that
      were inhibited by spironolactone. Comparable contractile responses were seen with
      both 17beta-estradiol and hydrocortisone. In total, these data are consistent
      with a mechanism of acute aldosterone-mediated contraction common to both
      glucocorticoids and estrogen. Steroid-mediated vasoconstriction may represent an
      important pathobiological mechanism of vascular disease, especially in the
      setting of preexisting endothelial dysfunction.

PMID- 16971491
TI  - Characterization of two splice variants of human organic anion transporting
      polypeptide 3A1 isolated from human brain.
AB  - In the present study we isolated two splice variants of organic anion
      transporting polypeptide 3A1 (OATP3A1_v1 and OATP3A1_v2) from human brain.
      OATP3A1_v2 lacks 18 amino acids (aa) at the COOH-terminal end (692 aa) but is
      otherwise similar in sequence to OATP3A1_v1 (710 aa). OATP3A1_v1 exhibits a wide
      tissue distribution, with expression in testis, various brain regions, heart,
      lung, spleen, peripheral blood leukocytes, and thyroid gland, whereas OATP3A1_v2
      is predominantly expressed in testis and brain. On the cellular and subcellular
      levels OATP3A1_v1 could be immunolocalized in testicular germ cells, the
      basolateral plasma membrane of choroid plexus epithelial cells, and neuroglial
      cells of the gray matter of human frontal cortex. Immunolocalization of
      OATP3A1_v2 included Sertoli cells in testis, apical and/or subapical membranes in
      choroid plexus epithelial cells, and neurons (cell bodies and axons) of the gray
      and white matter of human frontal cortex. The rodent ortholog Oatp3a1 was also
      widely distributed in rat brain, and its localization included somatoneurons as
      well as astroglial cells. Transport studies in cRNA-injected Xenopus laevis
      oocytes and in stably transfected Chinese hamster ovary FlpIn cells revealed a
      similar broad substrate specificity for both splice variants. Transported
      substrates include prostaglandin (PG)E(1) and PGE(2), thyroxine, and the cyclic
      oligopeptides BQ-123 (endothelin receptor antagonist) and vasopressin. These
      studies provide further evidence for the involvement of OATPs in oligopeptide
      transport. They specifically suggest that OATP3A1 variants might be involved in
      the regulation of extracellular vasopressin concentration in human brain and thus
      might influence the neuromodulation of neurotransmission by cerebral
      neuropeptides such as vasopressin.

PMID- 16971492
TI  - Methoxyflavones protect cells against endoplasmic reticulum stress and
      neurotoxin.
AB  - Enhanced endoplasmic reticulum (ER) stress leads to cell death in various
      pathophysiological situations. During a search for compounds that regulate ER
      stress, we identified methoxyflavones, a group of flavonoids, as strong
      protective agents against ER stress. Analysis in mouse insulinoma MIN6 cells
      revealed that methoxyflavones mildly activated the eukaryotic initiation factor
      2alpha and nuclear factor erythroid 2-related factor pathways, but not the XBP1
      pathway, and induced downstream genes, including glucose-regulated protein (GRP)
      78, a molecular chaperone in the ER. The protective effect of methoxyflavones was
      enhanced by agents that increase intracellular cAMP levels such as forskolin,
      dibutyryl-cAMP and IBMX, but suppressed by the protein kinase A (PKA) inhibitor H
      89, suggesting involvement of the PKA pathway in the regulation of ER stress by
      methoxyflavones. Consistent with the results in cultured cells, pretreatment of
      mice with tangeretin, a methoxyflavone, enhanced expression of GRP78 and HO-1
      without causing ER stress in renal tubular epithelium and prevented tunicamycin
      induced cell death. Furthermore, preadministration of tangeretin in mice enhanced
      expression of GRP78 in the substantia nigra pars compacta and protected
      dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a
      neurotoxin that induces both oxidative and ER stress. These results suggest that
      methoxyflavones play an important role in the regulation of ER stress and could
      be a therapeutic target for the ER stress-related diseases.

PMID- 16971493
TI  - The role of the activin system in keloid pathogenesis.
AB  - Keloid scars represent a pathological response to cutaneous injury under the
      regulation of many growth factors. Activin-A, a dimeric protein and a member of
      the transforming growth factor-beta superfamily, has been shown to regulate
      various aspects of cell growth and differentiation in the repair of the skin
      mesenchyme and the epidermis. Thus our aim was to study the role of activin and
      its antagonist, follistatin, in keloid pathogenesis. Increased mRNA expression
      for activin was observed in keloid scar tissue by performing RNase protection
      assay. Immunohistochemistry showed increased localization of both activin-A and
      follistatin in the basal layer of epidermis of keloid tissue compared with normal
      tissue. ELISA demonstrated a 29-fold increase in concentration of activin-A and
      an approximately 5-fold increase in follistatin in conditioned media in keloid
      fibroblasts compared with normal fibroblasts. Although keloid keratinocytes
      produced 25% more follistatin than normal keratinocytes, the amounts of activin
      A, in contrast, was approximately 77% lower. Proliferation of fibroblasts was
      stimulated when treated with exogenous activin-A (46% increase in keloids
      fibroblasts) or following co-culture with hbetaAHaCaT cells (66% increase).
      Activin-A upregulated key extracellular matrix components, namely collagen,
      fibronectin, and alpha-smooth muscle actin, in normal and keloid fibroblasts. Co
      treatment of follistatin with activin-A blocked the stimulatory effects of
      activin on extracellular matrix components. These findings emphasize the
      importance of the activin system in keloid biology and pathogenesis and suggest a
      possible therapeutic potential of follistatin in the prevention and treatment of
      keloids.

PMID- 16971494
TI  - Unique uptake and efflux systems of inorganic phosphate in osteoclast-like cells.
AB  - During bone resorption, a large amount of inorganic phosphate (P(i)) is generated
      within the osteoclast hemivacuole. The mechanisms involved in the disposal of
      this P(i) are not clear. In the present study, we investigated the efflux of P(i)
      from osteoclast-like cells. P(i) efflux was activated by acidic conditions in
      osteoclast-like cells derived by the treatment of RAW264.7 cells with receptor
      activator of nuclear factor-kappaB ligand. Acid-induced P(i) influx was not
      observed in renal proximal tubule-like opossum kidney cells, osteoblast-like
      MC3T3-E1 cells, or untreated RAW264.7 cells. Furthermore, P(i) efflux was
      stimulated by extracellular P(i) and several P(i) analogs [phosphonoformic acid
      (PFA), phosphonoacetic acid, arsenate, and pyrophosphate]. P(i) efflux was time
      dependent, with 50% released into the medium after 10 min. The efflux of P(i) was
      increased by various inhibitors that block P(i) uptake, and extracellular P(i)
      did not affect the transport of [(14)C]PFA into the osteoclast-like cells.
      Preloading of cells with P(i) did not stimulate P(i) efflux by PFA, indicating
      that the effect of P(i) was not due to transstimulation of P(i) transport. P(i)
      uptake was also enhanced under acidic conditions. Agents that prevent increases
      in cytosolic free Ca(2+) concentration, including acetoxymethyl ester of 1,2
      bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, 2-aminoethoxydiphenyl
      borate, and bongkrekic acid, significantly inhibited P(i) uptake in the
      osteoclast-like cells, suggesting that P(i) uptake is regulated by Ca(2+)
      signaling in the endoplasmic reticulum and mitochondria of osteoclast-like cells.
      These results suggest that osteoclast-like cells have a unique P(i) uptake/efflux
      system and can prevent P(i) accumulation within osteoclast hemivacuoles.

PMID- 16971496
TI  - Stable overexpression of human macrophage cholesteryl ester hydrolase results in
      enhanced free cholesterol efflux from human THP1 macrophages.
AB  - Reduction of the lipid burden of atherosclerotic lesion-associated macrophage
      foam cells is a logical strategy to reduce the plaque volume. Since extracellular
      cholesterol acceptor-mediated cholesterol efflux is the only recognized mechanism
      of cholesterol removal from foam cells and this process is rate limited at the
      level of intracellular cholesterol ester hydrolysis, a reaction catalyzed by
      neutral cholesteryl ester hydrolase (CEH), we examined the hypothesis that CEH
      overexpression in the human macrophage monocyte/macrophage cell line THP1 results
      in increased cholesterol efflux, as well as decreased cellular cholesterol ester
      accumulation. We generated THP1-CEH cells with stable integration of human
      macrophage CEH cDNA driven by the cytomegalovirus promoter. Compared with wild
      type THP1 cells (THP1-WT), THP1-CEH cells showed increased CEH mRNA expression
      and increased CEH activity. Efflux of free or unesterified cholesterol by
      acetylated LDL-loaded THP1-CEH cells to ApoA-I by an ABCA1-dependent pathway or
      to HDL by an ABCG1-dependent pathway was significantly higher than that in THP1
      WT cells. In addition, THP1-CEH cells accumulated significantly lower amount of
      esterified cholesterol. CEH overexpression, therefore, not only enhances
      cholesterol efflux but also reduces cellular accumulation of cholesteryl esters.
      Taken together, these data provide evidence for evaluating CEH expression in
      human macrophages as a potential target for attenuation of foam cell formation
      and regression of atherosclerotic plaques.

PMID- 16971495
TI  - Acute activation of NHE3 by dexamethasone correlates with activation of SGK1 and
      requires a functional glucocorticoid receptor.
AB  - Glucocorticoids stimulate the intestinal absorption of Na(+) and water partly by
      regulation of the Na(+)/H(+) exchanger 3 (NHE3). Previous studies have shown both
      genomic and nongenomic regulation of NHE3 by glucocorticoids. Serum and
      glucocorticoid-inducible kinase 1 (SGK1) has been shown to be part of this
      cascade, where phosphorylation of NHE3 by SGK1 initiates the translocation of
      NHE3 to the cell surface. In the present work, we examined a series of changes in
      SGK1 and NHE3 induced by glucocorticoids using human colonic Caco-2 and opossum
      kidney cells. We found that dexamethasone rapidly stimulated SGK1 mRNAs, but a
      significant change in protein abundance was not detected. Instead, there was an
      increase in SGK1 kinase activity as early as at 2 h. An increase in NHE3 protein
      abundance was not detected until 12 h of dexamethasone exposure, although the
      transport activity was significantly stimulated at 4 h. These data demonstrate
      that the changes of SGK1 precede those of NHE3. Chronic regulation (24 h) of NHE3
      was blocked completely by prevention of protein synthesis with cycloheximide or
      actinomycin D and by the glucocorticoid receptor blocker RU486. The acute effect
      of dexamethasone was similarly abrogated by RU486, but was insensitive to
      cycloheximide and actinomycin D. Similarly, the stimulation of SGK1 activity by
      dexamethasone was blocked by RU486 but not by actinomycin D. Together, these data
      show that the acute effect of glucocorticoids on NHE3 is mediated by a
      glucocorticoid receptor dependent mechanism that activates SGK1 in a nongenomic
      manner.

PMID- 16971497
TI  - Mg2+ activates the ryanodine receptor type 2 (RyR2) at intermediate Ca2+
      concentrations.
AB  - To clarify whether activity of the ryanodine receptor type 2 (RyR2) is reduced in
      the sarcoplasmic reticulum (SR) of cardiac muscle, as is the case with the
      ryanodine receptor type 1 (RyR1), Ca(2+)-dependent [(3)H]ryanodine binding, a
      biochemical measure of Ca(2+)-induced Ca(2+) release (CICR), was determined using
      SR vesicle fractions isolated from rabbit and rat cardiac muscles. In the absence
      of an adenine nucleotide or caffeine, the rat SR showed a complicated Ca(2+)
      dependence, instead of the well-documented biphasic dependence of the rabbit SR.
      In the rat SR, [(3)H]ryanodine binding initially increased as [Ca(2+)] increased,
      with a plateau in the range of 10-100 microM Ca(2+), and thereafter further
      increased to an apparent peak around 1 mM Ca(2+), followed by a decrease. In the
      presence of these modulators, this complicated dependence prevailed, irrespective
      of the source. Addition of 0.3-1 mM Mg(2+) unexpectedly increased the binding two
      to threefold and enhanced the affinity for [(3)H]ryanodine at 10-100 microM
      Ca(2+), resulting in the well-known biphasic dependence. In other words, the
      partial suppression of RyR2 is relieved by Mg(2+). Ca(2+) could be a substitute
      for Mg(2+). Mg(2+) also amplifies the responses of RyR2 to inhibitory and
      stimulatory modulators. This stimulating effect of Mg(2+) on RyR2 is entirely
      new, and is referred to as the third effect, in addition to the well-known dual
      inhibitory effects. This effect is critical to describe the role of RyR2 in
      excitation-contraction coupling of cardiac muscle, in view of the intracellular
      Mg(2+) concentration.

PMID- 16971498
TI  - Modulation of electron transport protects cardiac mitochondria and decreases
      myocardial injury during ischemia and reperfusion.
AB  - Mitochondria are increasingly recognized as lynchpins in the evolution of cardiac
      injury during ischemia and reperfusion. This review addresses the emerging
      concept that modulation of mitochondrial respiration during and immediately
      following an episode of ischemia can attenuate the extent of myocardial injury.
      The blockade of electron transport and the partial uncoupling of respiration are
      two mechanisms whereby manipulation of mitochondrial metabolism during ischemia
      decreases cardiac injury. Although protection by inhibition of electron transport
      or uncoupling of respiration initially appears to be counterintuitive, the
      continuation of mitochondrial oxidative phosphorylation in the pathological
      milieu of ischemia generates reactive oxygen species, mitochondrial calcium
      overload, and the release of cytochrome c. The initial target of these
      deleterious mitochondrial-driven processes is the mitochondria themselves.
      Consequences to the cardiomyocyte, in turn, include oxidative damage, the onset
      of mitochondrial permeability transition, and activation of apoptotic cascades,
      all favoring cardiomyocyte death. Ischemia-induced mitochondrial damage carried
      forward into reperfusion further amplifies these mechanisms of mitochondrial
      driven myocyte injury. Interruption of mitochondrial respiration during early
      reperfusion by pharmacologic blockade of electron transport or even recurrent
      hypoxia or brief ischemia paradoxically decreases cardiac injury. It increasingly
      appears that the cardioprotective paradigms of ischemic preconditioning and
      postconditioning utilize modulation of mitochondrial oxidative metabolism as a
      key effector mechanism. The initially counterintuitive approach to inhibit
      mitochondrial respiration provides a new cardioprotective paradigm to decrease
      cellular injury during both ischemia and reperfusion.

PMID- 16971499
TI  - Multiparameter metabolic analysis reveals a close link between attenuated
      mitochondrial bioenergetic function and enhanced glycolysis dependency in human
      tumor cells.
AB  - Increased conversion of glucose to lactic acid associated with decreased
      mitochondrial respiration is a unique feature of tumors first described by Otto
      Warburg in the 1920s. Recent evidence suggests that the Warburg effect is caused
      by oncogenes and is an underlying mechanism of malignant transformation. Using a
      novel approach to measure cellular metabolic rates in vitro, the bioenergetic
      basis of this increased glycolysis and reduced mitochondrial respiration was
      investigated in two human cancer cell lines, H460 and A549. The bioenergetic
      phenotype was analyzed by measuring cellular respiration, glycolysis rate, and
      ATP turnover of the cells in response to various pharmacological modulators. H460
      and A549 cells displayed a dependency on glycolysis and an ability to
      significantly upregulate this pathway when their respiration was inhibited. The
      converse, however, was not true. The cell lines were attenuated in oxidative
      phosphorylation (OXPHOS) capacity and were unable to sufficiently upregulate
      mitochondrial OXPHOS when glycolysis was disabled. This observed mitochondrial
      impairment was intimately linked to the increased dependency on glycolysis.
      Furthermore, it was demonstrated that H460 cells were more glycolytic, having a
      greater impairment of mitochondrial respiration, compared with A549 cells.
      Finally, the upregulation of glycolysis in response to mitochondrial ATP
      synthesis inhibition was dependent on AMP-activated protein kinase activity. In
      summary, our results demonstrate a bioenergetic phenotype of these two cancer
      cell lines characterized by increased rate of glycolysis and a linked attenuation
      in their OXPHOS capacity. These metabolic alterations provide a mechanistic
      explanation for the growth advantage and apoptotic resistance of tumor cells.

PMID- 16971500
TI  - Modeling mitochondrial function.
AB  - The mitochondrion represents a unique opportunity to apply mathematical modeling
      to a complex biological system. Understanding mitochondrial function and control
      is important since this organelle is critical in energy metabolism as well as
      playing key roles in biochemical synthesis, redox control/signaling, and
      apoptosis. A mathematical model, or hypothesis, provides several useful insights
      including a rigorous test of the consensus view of the operation of a biological
      process as well as providing methods of testing and creating new hypotheses. The
      advantages of the mitochondrial system for applying a mathematical model include
      the relative simplicity and understanding of the matrix reactions, the ability to
      study the mitochondria as a independent contained organelle, and, most
      importantly, one can dynamically measure many of the internal reaction
      intermediates, on line. The developing ability to internally monitor events
      within the metabolic network, rather than just the inflow and outflow, is
      extremely useful in creating critical bounds on complex mathematical models using
      the individual reaction mechanisms available. However, many serious problems
      remain in creating a working model of mitochondrial function including the
      incomplete definition of metabolic pathways, the uncertainty of using in vitro
      enzyme kinetics, as well as regulatory data in the intact system and the unknown
      chemical activities of relevant molecules in the matrix. Despite these formidable
      limitations, the advantages of the mitochondrial system make it one of the best
      defined mammalian metabolic networks that can be used as a model system for
      understanding the application and use of mathematical models to study biological
      systems.

PMID- 16971501
TI  - Analysis of DHE-derived oxidation products by HPLC in the assessment of
      superoxide production and NADPH oxidase activity in vascular systems.
AB  - Dihydroethidium (DHE) is a widely used sensitive superoxide (O2(*-)) probe.
      However, DHE oxidation yields at least two fluorescent products, 2
      hydroxyethidium (EOH), known to be more specific for O2(*-), and the less
      specific product ethidium. We validated HPLC methods to allow quantification of
      DHE products in usual vascular experimental situations. Studies in vitro showed
      that xanthine/xanthine oxidase, and to a lesser degree peroxynitrite/carbon
      dioxide system led to EOH and ethidium formation. Peroxidase/H2O2 but not H2O2
      alone yielded ethidium as the main product. In vascular smooth muscle cells
      incubated with ANG II (100 nM, 4 h), we showed a 60% increase in EOH/DHE ratio,
      prevented by PEG-SOD or SOD1 overexpression. We further validated a novel DHE
      based NADPH oxidase assay in vascular smooth muscle cell membrane fractions,
      showing that EOH was uniquely increased after ANG II. This assay was also adapted
      to a fluorescence microplate reader, providing results in line with HPLC results.
      In injured artery slices, shown to exhibit increased DHE-derived fluorescence at
      microscopy, there was approximately 1.5- to 2-fold increase in EOH/DHE and
      ethidium/DHE ratios after injury, and PEG-SOD inhibited only EOH formation. We
      found that the amount of ethidium product and EOH/ethidium ratios are influenced
      by factors such as cell density and ambient light. In addition, we indirectly
      disclosed potential roles of heme groups and peroxidase activity in ethidium
      generation. Thus HPLC analysis of DHE-derived oxidation products can improve
      assessment of O2(*-) production or NADPH oxidase activity in many vascular
      experimental studies.

PMID- 16971502
TI  - Functional consequences of mitochondrial proteome heterogeneity.
AB  - Potential functional consequences of the differences in protein distribution
      between the mitochondria of the rat liver, heart, brain, and kidney, as
      determined in the companion paper in this issue (Johnson DT, French S, Blair PV,
      You JS, Bemis KG, Wang M, Harris RA, and Balaban RS. The tissue heterogeneity of
      the mammalian mitochondrial proteome. Am J Physiol Cell Physiol292: C689-C697,
      2006), were analyzed using a canonical metabolic pathway approach as well as a
      functional domain homology analysis. These data were inserted into the Kyoto
      Encyclopedia of Genes and Genomes pathway framework to give global and metabolic
      pathway-specific information on the impact of the differential protein
      distribution on mitochondrial function. Custom pathway analysis was also
      performed using pathways limited to the mitochondrion. With the use of this
      approach, several well-known functional differences between these mitochondrial
      populations were confirmed. These included GABA metabolism in the brain, urea
      synthesis in the liver, and the domination of oxidative phosphorylation in the
      heart. By comparing relative protein amounts of mitochondria across tissues, a
      greater understanding of functional emphasis is possible as well as the nuclear
      "programming" required to enhance a given function within the mitochondria. For
      proteins determined to be mitochondrial and lacking a defined role functional
      domain BLAST analyses were performed. Several proteins associated with DNA
      structural modification and a novel CoA transferase were identified. A protein
      was also identified capable of catalyzing the first three steps of de novo
      pyrimidine synthesis. This analysis demonstrates that the distribution of nuclear
      encoded proteins significantly modifies the overall functional emphasis of the
      mitochondria to meet tissue-specific needs. These studies demonstrate the
      existence of mitochondrial biochemical functions that at present are poorly
      defined.

PMID- 16971503
TI  - Estradiol protects against ethanol-induced bone loss by inhibiting up-regulation
      of receptor activator of nuclear factor-kappaB ligand in osteoblasts.
AB  - To investigate the effects of sex hormones on ethanol (EtOH)-induced bone loss,
      female Sprague-Dawley rats were fed control or EtOH-containing diets (12
      g/kg/day) by intragastric infusion. After 3 weeks, rats receiving EtOH had
      significant decreases in tibial trabecular and total bone mineral density,
      induction of receptor activator of nuclear factor-kappaB ligand (RANKL) mRNA
      expression, and enhanced bone resorption, all of which were prevented by
      treatment with 17beta-estradiol (E(2)). The addition of progesterone did not
      enhance the beneficial effect of E(2) alone. Consistent with our in vivo
      findings, EtOH stimulated RANKL mRNA expression in cultured primary osteoblasts,
      and this expression was blocked by 4-methylpyrazole. Acetaldehyde also induced
      RANKL expression. Class 1 alcohol dehydrogenase was found to be expressed and
      EtOH-inducible in cultured osteoblasts, whereas CYP2E1 was undetectable. We found
      that EtOH induced phosphorylation of extracellular signal-regulated kinase (ERK)
      and signal transducers and activators of transcription 3 (STAT3). E(2) and the
      mitogenactivated protein kinase kinase inhibitor 2'-amino-3'-methoxyflavone
      (PD98059) blocked ERK and STAT3 phosphorylation and blocked RANKL induction.
      Moreover, E(2) completely blocked EtOH-induced osteoclastogenesis in a primary
      osteoblast and osteoclast precursor coculture system. The E(2) effects were
      estrogen receptor-mediated. Therefore, E(2) prevents EtOH-induced bone loss by
      opposing the induction of RANKL mRNA in osteoblasts and ethanol-induced
      osteoclastogenesis, through opposing effects on sustained ERK signaling.

PMID- 16971504
TI  - The anxioselective agent 7-(2-chloropyridin-4-yl)pyrazolo-[1,5-a]-pyrimidin-3
      yl](pyridin-2-yl)methanone (DOV 51892) is more efficacious than diazepam at
      enhancing GABA-gated currents at alpha1 subunit-containing GABAA receptors.
AB  - Studies using mice with point mutations of GABA(A) receptor alpha subunits
      suggest that the sedative and anxiolytic properties of 1,4-benzodiazepines are
      mediated, respectively, by GABA(A) receptors bearing the alpha(1) and alpha(2)
      subunits. This hypothesis predicts that a compound with high efficacy at GABA(A)
      receptors containing the alpha(1) subunit would produce sedation, whereas an
      agonist acting at alpha(2) subunit-containing receptors (with low or null
      efficacy at alpha(1)-containing receptors) would be anxioselective.
      Electrophysiological studies using recombinant GABA(A) receptors expressed in
      Xenopus oocytes indicate that maximal potentiation of GABA-stimulated currents by
      the pyrazolo-[1,5-a]-pyrimidine, DOV 51892, at alpha(1)beta(2)gamma(2S)
      constructs of the GABA(A) receptor was significantly higher (148%) than diazepam.
      In contrast, DOV 51892 was considerably less efficacious and/or potent than
      diazepam in enhancing GABA-stimulated currents mediated by constructs containing
      alpha(2), alpha(3), or alpha(5) subunits. In vivo, DOV 51892 increased punished
      responding in the Vogel conflict test, an effect blocked by flumazenil, and
      increased the percentage of time spent in the open arms of the elevated plus
      maze. However, DOV 51892 had no consistent effects on motor function or muscle
      relaxation at doses more than 1 order of magnitude greater than the minimal
      effective anxiolytic dose. Although the mutant mouse data predict that the high
      efficacy potentiation of GABA(A1a) receptor-mediated currents by DOV 51892 would
      be sedating, behavioral studies demonstrate that DOV 51892 is anxioselective,
      indicating that GABA potentiation mediated by alpha(1) subunit-containing GABA(A)
      receptors may be neither the sole mechanism nor highly predictive of the sedative
      properties of benzodiazepine recognition site modulators.

PMID- 16971505
TI  - Altered calcium/calmodulin kinase II activity changes calcium homeostasis that
      underlies epileptiform activity in hippocampal neurons in culture.
AB  - Epilepsy is characterized by the occurrence of spontaneous recurrent epileptiform
      discharges (SREDs) in neurons. A decrease in calcium/calmodulin-dependent protein
      kinase II (CaMK-II) activity has been shown to occur with the development of
      SREDs in a hippocampal neuronal culture model of acquired epilepsy, and altered
      calcium (Ca(2+)) homeostasis has been implicated in the development of SREDs.
      Using antisense oligonucleotides, this study was conducted to determine whether
      selective suppression of CaMK-II activity, with subsequent induction of SREDs,
      was associated with altered Ca(2+) homeostasis in hippocampal neurons in culture.
      Antisense knockdown resulted in the development of SREDs and a decrease in both
      immunocytochemical staining and enzyme activity of CaMK-II. Evaluation of
      [Ca(2+)](i) using Fura indicators revealed that antisense-treated neurons
      manifested increased basal [Ca(2+)](i), whereas missense-treated neurons showed
      no change in basal [Ca(2+)](i). Antisense suppression of CaMK-II was also
      associated with an inability of neurons to restore a Ca(2+) load. Upon removal of
      oligonucleotide treatment, CaMK-II suppression and Ca(2+) homeostasis recovered
      to control levels and SREDs were abolished. To our knowledge, the results
      demonstrate the first evidence that selective suppression of CaMK-II activity
      results in alterations in Ca(2+) homeostasis and the development of SREDs in
      hippocampal neurons and suggest that CaMK-II suppression may be causing
      epileptogenesis by altering Ca(2+) homeostatic mechanisms.

PMID- 16971506
TI  - Cycloheximide protects HepG2 cells from serum withdrawal-induced apoptosis by
      decreasing p53 and phosphorylated p53 levels.
AB  - Cycloheximide (CHX), an inhibitor of protein synthesis, has been reported to
      prevent cell death in a wide variety of cell types and produced by different
      apoptotic stimuli. However, the mechanisms by which CHX protects cells from
      apoptosis are still unclear. In this study, we investigated whether p53 plays a
      role in the protection by CHX against serum withdrawal-induced apoptosis.
      Deprivation of serum from the culture medium causes apoptosis in HepG2 cells, and
      CHX dramatically protects cells from death. p53, p21, and Bax protein levels were
      elevated, and cell cycle arrest was produced after serum withdrawal. CHX
      abolished this elevation of p53, p21, and Bax as well as the cell cycle arrest
      induced by serum deprivation. The p53 inhibitor pifithrin-alpha protects HepG2
      cells against apoptosis induced by serum withdrawal. HepG2 cells expressing a
      dominant negative form of mutant p53 and Hep3B cells lacking p53 were resistant
      to serum withdrawal-induced apoptosis. Lowering of p53 by small interfering RNA
      protects HepG2 cells from serum withdrawal-induced apoptosis. p53 phosphorylation
      was induced by serum withdrawal and other chemotherapeutic reagents such as
      actinomycin D, doxorubicin, and etoposide. CHX decreases the levels of
      phosphorylated p53 (pp53) even in the presence of a proteasome inhibitor, which
      maintains the total p53 levels, whereas it does not affect the dephosphorylation
      of pp53. These results suggest the possibility that kinases that phosphorylate
      p53 might be affected by CHX administration. In summary, CHX protects HepG2 cells
      from serum withdrawal-induced apoptosis through inhibiting the synthesis of p53
      and the phosphorylation of p53.

PMID- 16971507
TI  - Proteasome inhibitors potentiate etoposide-induced cell death in human
      astrocytoma cells bearing a mutated p53 isoform.
AB  - Resistance to anticancer agents is often due to defects of intracellular pathways
      of cell death. Thus, the identification of the apoptotic pathways that can still
      be recruited by chemotherapeutic agents in cancerous cells can disclose new
      opportunities to treat malignancies. Here we show that human astrocytoma ADF
      cells (which are resistant to "mitochondriotropic" agents as well as to the
      antineoplastic drug etoposide and to proteasome inhibitors when used alone)
      undergo dramatic apoptotic death when exposed to a combination protocol based on
      the use of etoposide in the presence of proteasome inhibitors. Sensitization to
      cell death involved an autoamplifying loop of caspase activation, where the
      "executioner" phase of apoptosis was sustained by cooperation of caspase-2, -9, 
      8, and -3. We also show that sensitization of cells to the combination protocol
      involved the nuclear relocalization of p53, despite the presence of a
      polymorphism in its DNA-binding domain, suggesting the likely induction of p53
      dependent proapoptotic genes. Conversely, p53 phosphorylation on Ser-15 did not
      play any role in apoptosis. In conclusion, use of etoposide in combination with
      proteasome inhibitors may represent an effective strategy to restore sensitivity
      to apoptosis in human astrocytoma cells bearing multiple defects of intracellular
      apoptotic pathways.

PMID- 16971508
TI  - Hepatocellular toxicity and pharmacological effect of amiodarone and amiodarone
      derivatives.
AB  - The aim of this work was to compare hepatocellular toxicity and pharmacological
      activity of amiodarone (2-n-butyl-3-[3,5 diiodo-4-diethylaminoethoxybenzoyl]
      benzofuran; B2-O-Et-N-diethyl) and of eight amiodarone derivatives. Three
      amiodarone metabolites were studied, namely, mono-N-desethylamiodarone (B2-O-Et
      NH-ethyl), di-N-desethylamiodarone (B2-O-Et-NH(2)), and (2-butyl-benzofuran-3-yl)
      (4-hydroxy-3,5-diiodophenyl)-methanone (B2) carrying an ethanol side chain [(2
      butylbenzofuran-3-yl)-[4-(2-hydroxyethoxy)-3,5-diiodophenyl]-methanone; B2-O-Et
      OH]. In addition, five amiodarone analogs were investigated, namely, N
      dimethylamiodarone (B2-O-Et-N-dimethyl), N-dipropylamiodarone (B2-O-Et-N
      dipropyl), B2-O-carrying an acetate side chain [[4-(2-butyl-benzofuran-3
      carbonyl)-2,6-diiodophenyl]-acetic acid; B2-O-acetate], B2-O-Et carrying an
      propionamide side chain (B2-O-Et-propionamide), and B2-O carrying an ethyl side
      chain [(2-butylbenzofuran-3-yl)-(4-ethoxy-3,5-diiodophenyl)-methanone; B2-O-Et].
      A concentration-dependent increase in lactate dehydrogenase leakage from HepG2
      cells and isolated rat hepatocytes was observed in the presence of amiodarone and
      of most analogs, confirming their hepatocellular toxicity. Using freshly isolated
      rat liver mitochondria, amiodarone and most analogs showed a dose-dependent
      toxicity on the respiratory chain and on beta-oxidation, significantly reducing
      the respiratory control ratio and oxidation of palmitate, respectively. The
      reactive oxygen species concentration in hepatocytes increased time-dependently,
      and apoptotic/necrotic cell populations were identified using flow cytometry and
      annexin V/propidium iodide staining. The effect of the three least toxic
      amiodarone analogs on the human ether-a-go-go-related gene (hERG) channel was
      compared with amiodarone. Amiodarone, B2-O-acetate, and B2-O-Et-N-dipropyl (each
      10 microM) significantly reduced the hERG tail current amplitude, whereas 10
      microM B2-O-Et displayed no detectable effect on hERG outward potassium currents.
      In conclusion, three amiodarone analogs (B2-O-Et-N-dipropyl, B2-O-acetate, and B2
      O-Et) showed a lower hepatocellular toxicity profile than amiodarone, and two of
      these analogs (B2-O-Et-N-dipropyl and B2-O-acetate) retained hERG channel
      interaction capacity, suggesting that amiodarone analogs with class III
      antiarrhythmic activity and lower hepatic toxicity could be developed.

PMID- 16971509
TI  - A critical role for the membrane-type 1 matrix metalloproteinase in collagen
      phagocytosis.
AB  - Degradation of collagen is important for the physiological remodeling of
      connective tissues during growth and development as well as in wound healing,
      inflammatory diseases, and cancer cell invasion. In remodeling adult tissues,
      degradation of collagen occurs primarily through a phagocytic pathway. However,
      although various steps in the phagocytic pathway have been characterized, the
      enzyme required to initially fragment collagen fibrils for subsequent
      phagocytosis has not been identified. We have used laser confocal microscopy,
      transmission electron microscopy, and biochemical assays to show that human
      fibroblasts initiate degradation of collagen through the collagenase activity of
      the membrane-bound metalloproteinase MT1-MMP. Degradation of natural and
      reconstituted collagen substrates correlated with the expression of MT1-MMP,
      which was localized at sites of collagen cleavage at the surface of the cells and
      also within the cells, whereas collagen degradation was abrogated when MT1-MMP
      expression was blocked by small interfering RNA treatment. In contrast to MT1
      MMP, the gelatinolytic activity of MMP-2 was not required for collagen
      phagocytosis. These studies demonstrate a pivotal role of catalytically active
      MT1-MMP in preparing collagen fibrils for phagocytic degradation.

PMID- 16971510
TI  - Myo1c binds phosphoinositides through a putative pleckstrin homology domain.
AB  - Myo1c is a member of the myosin superfamily that binds phosphatidylinositol-4,5
      bisphosphate (PIP(2)), links the actin cytoskeleton to cellular membranes and
      plays roles in mechano-signal transduction and membrane trafficking. We located
      and characterized two distinct membrane binding sites within the regulatory and
      tail domains of this myosin. By sequence, secondary structure, and ab initio
      computational analyses, we identified a phosphoinositide binding site in the tail
      to be a putative pleckstrin homology (PH) domain. Point mutations of residues
      known to be essential for polyphosphoinositide binding in previously
      characterized PH domains inhibit myo1c binding to PIP(2) in vitro, disrupt in
      vivo membrane binding, and disrupt cellular localization. The extended sequence
      of this binding site is conserved within other myosin-I isoforms, suggesting they
      contain this putative PH domain. We also characterized a previously identified
      membrane binding site within the IQ motifs in the regulatory domain. This region
      is not phosphoinositide specific, but it binds anionic phospholipids in a calcium
      dependent manner. However, this site is not essential for in vivo membrane
      binding.

PMID- 16971511
TI  - Mechanically induced actin-mediated rocketing of phagosomes.
AB  - Actin polymerization can be induced in Dictyostelium by compressing the cells to
      bring phagosomes filled with large particles into contact with the plasma
      membrane. Asymmetric actin assembly results in rocketing movement of the
      phagosomes. We show that the compression-induced assembly of actin at the
      cytoplasmic face of the plasma membrane involves the Arp2/3 complex. We also
      identify two other proteins associated with the mechanically induced actin
      assembly. The class I myosin MyoB accumulates at the plasma membrane-phagosome
      interface early during the initiation of the response, and coronin is recruited
      as the actin filaments are disassembling. The forces generated by rocketing
      phagosomes are sufficient to push the entire microtubule apparatus forward and to
      dislocate the nucleus.

PMID- 16971512
TI  - Loss of T-cell protein tyrosine phosphatase induces recycling of the platelet
      derived growth factor (PDGF) beta-receptor but not the PDGF alpha-receptor.
AB  - We have previously shown that the T-cell protein tyrosine phosphatase (TC-PTP)
      dephosphorylates the platelet-derived growth factor (PDGF) beta-receptor. Here,
      we show that the increased PDGF beta-receptor phosphorylation in TC-PTP knockout
      (ko) mouse embryonic fibroblasts (MEFs) occurs primarily on the cell surface. The
      increased phosphorylation is accompanied by a TC-PTP-dependent, monensin
      sensitive delay in clearance of cell surface PDGF beta-receptors and delayed
      receptor degradation, suggesting PDGF beta-receptor recycling. Recycled receptors
      could also be directly detected on the cell surface of TC-PTP ko MEFs. The effect
      of TC-PTP depletion was specific for the PDGF beta-receptor, because PDGF alpha
      receptor homodimers were cleared from the cell surface at the same rate in TC-PTP
      ko MEFs as in wild-type MEFs. Interestingly, PDGF alphabeta-receptor heterodimers
      were recycling. Analysis by confocal microscopy revealed that, in TC-PTP ko MEFs,
      activated PDGF beta-receptors colocalized with Rab4a, a marker for rapid
      recycling. In accordance with this, transient expression of a dominant-negative
      Rab4a construct increased the rate of clearance of cell surface receptors on TC
      PTP ko MEFs. Thus, loss of TC-PTP specifically redirects the PDGF beta-receptor
      toward rapid recycling, which is the first evidence of differential trafficking
      of PDGF receptor family members.

PMID- 16971513
TI  - Critical role of PICT-1, a tumor suppressor candidate, in phosphatidylinositol
      3,4,5-trisphosphate signals and tumorigenic transformation.
AB  - The tumor suppressor phosphatase and tensin homolog deleted on chromosome 10
      (PTEN) regulates diverse cellular functions by dephosphorylating the lipid second
      messenger, phosphatidylinositol 3,4,5-trisphosphate (PIP(3)). Recent study
      revealed that PICT-1/GLTSCR2 bound to and stabilized PTEN protein in cells,
      implicating its roles in PTEN-governed PIP(3) signals. In this study, we
      demonstrate that RNA interference-mediated knockdown of PICT-1 in HeLa cells down
      regulated endogenous PTEN and resulted in the activation of PIP(3) downstream
      effectors, such as protein kinase B/Akt. Furthermore, the PICT-1 knockdown
      promoted HeLa cell proliferation; however the proliferation of PTEN-null cells
      was not altered by the PICT-1 knockdown, suggesting its dependency on PTEN
      status. In addition, apoptosis of HeLa cells induced by staurosporine or serum
      depletion was alleviated by the PICT-1 knockdown in the similar PTEN-dependent
      manner. Most strikingly, the PICT-1 knockdown in HeLa and NIH3T3 cells promoted
      anchorage-independent growth, a hallmark of tumorigenic transformation.
      Furthermore, PICT-1 was aberrantly expressed in 18 (41%) of 44 human
      neuroblastoma specimens, and the PICT-1 loss was associated with reduced PTEN
      protein expression in spite of the existence of PTEN mRNA. Collectively, these
      results suggest that PICT-1 plays a role in PIP(3) signals through controlling
      PTEN protein stability and the impairment in the PICT-1-PTEN regulatory unit may
      become a causative factor in human tumor(s).

PMID- 16971514
TI  - Integrin signaling through Arg activates p190RhoGAP by promoting its binding to
      p120RasGAP and recruitment to the membrane.
AB  - The Rho family GTPases RhoA (Rho), Rac1, and Cdc42 are essential effectors of
      integrin-mediated cell attachment and spreading. Rho activity, which promotes
      formation of focal adhesions and actin stress fibers, is inhibited upon initial
      cell attachment to allow sampling of the new adhesive environment. The Abl
      related gene (Arg) tyrosine kinase mediates adhesion-dependent inhibition of Rho
      through phosphorylation and activation of the Rho inhibitor p190RhoGAP-A (p190).
      p190 phosphorylation promotes its binding to p120RasGAP (p120). Here, we
      elucidate the mechanism by which p120 binding regulates p190 activation after
      adhesion. We show that p190 requires its p120-binding domain to undergo Arg
      dependent activation in vivo. However, p120 binding does not activate p190RhoGAP
      activity in vitro. Instead, activation of p190 requires recruitment to the cell
      periphery. Integrin-mediated adhesion promotes relocalization of p190 and p120 to
      the cell periphery in wild-type fibroblasts, but not in arg(-/-) fibroblasts. A
      dominant-negative p120 fragment blocks p190:p120 complex formation, prevents
      activation of p190 by adhesion, and disrupts the adhesion-dependent recruitment
      of p190 to the cell periphery. Our results demonstrate that integrin signaling
      through Arg activates p190 by promoting its association with p120, resulting in
      recruitment of p190 to the cell periphery where it inhibits Rho.

PMID- 16971515
TI  - LET-711, the Caenorhabditis elegans NOT1 ortholog, is required for spindle
      positioning and regulation of microtubule length in embryos.
AB  - Spindle positioning is essential for the segregation of cell fate determinants
      during asymmetric division, as well as for proper cellular arrangements during
      development. In Caenorhabditis elegans embryos, spindle positioning depends on
      interactions between the astral microtubules and the cell cortex. Here we show
      that let-711 is required for spindle positioning in the early embryo. Strong loss
      of let-711 function leads to sterility, whereas partial loss of function results
      in embryos with defects in the centration and rotation movements that position
      the first mitotic spindle. let-711 mutant embryos have longer microtubules that
      are more cold-stable than in wild type, a phenotype opposite to the short
      microtubule phenotype caused by mutations in the C. elegans XMAP215 homolog ZYG
      9. Simultaneous reduction of both ZYG-9 and LET-711 can rescue the centration and
      rotation defects of both single mutants. let-711 mutant embryos also have larger
      than wild-type centrosomes at which higher levels of ZYG-9 accumulate compared
      with wild type. Molecular identification of LET-711 shows it to be an ortholog of
      NOT1, the core component of the CCR4/NOT complex, which plays roles in the
      negative regulation of gene expression at transcriptional and post
      transcriptional levels in yeast, flies, and mammals. We therefore propose that
      LET-711 inhibits the expression of ZYG-9 and potentially other centrosome
      associated proteins, in order to maintain normal centrosome size and microtubule
      dynamics during early embryonic divisions.

PMID- 16971516
TI  - Dark immunofluorescence: correlation with serum immunoglobulin abnormalities.
AB  - Occasional serum samples (<0.5%) tested by indirect immunofluorescence showed
      less fluorescence than did negative-control serum. A retrospective review of
      these patients' serum immunoglobulins revealed a high percentage of abnormalities
      (71%, versus 22% of controls). We suggest that this observation should be
      reported when seen and that the clinician should be alerted to an association
      with immunoglobulin abnormalities.

PMID- 16971517
TI  - Measurement of plasma-derived substance P: biological, methodological, and
      statistical considerations.
AB  - The undecapeptide substance P (SP) is a member of the tachykinin family of
      neurotransmitters, which has a pivotal role in the regulation of inflammatory and
      immune responses. One of the major barriers to the study of the in vivo role of
      SP in a number of immune disorders is the accurate measurement of SP in fluids.
      This is reflected in the variability of reported SP levels in serum and plasma of
      humans in both healthy and diseased states. This study was initiated in order to
      identify sources of variability by the comparative evaluation of the influences
      of sample preparation and analytical detection methods on the measurement of SP
      in plasma. The results indicate that sample preparation (peptide extraction
      versus no extraction) and the choice of analytical method for SP quantitation may
      yield significantly different values and may contribute to the variability in SP
      values reported in the literature. These results further emphasize the need for
      careful consideration in the selection of methods for SP quantitation, as well as
      caution in the interpretation and comparison of data reported in the literature.

PMID- 16971518
TI  - Will research sharing keep pace with the Internet?

PMID- 16971519
TI  - Molecular physiology of the neural circuit for calcineurin-dependent associative
      learning in Caenorhabditis elegans.
AB  - How learning and memory is controlled at the neural circuit level is a
      fundamental question in neuroscience. However, molecular and cellular dissection
      of the neural circuits underlying learning and memory is extremely complicated in
      higher animals. Here, we report a simple neural circuit for learning behavior in
      Caenorhabditis elegans, where the calcium-activated phosphatase, calcineurin,
      acts as an essential modulator. The calcineurin mutant tax-6 showed defective
      feeding state-dependent learning behavior for temperature and salt. Surprisingly,
      defective associative learning between temperature and feeding state was caused
      by malfunctions of two pairs of directly connected interneurons, AIZ and RIA, in
      the mature nervous system. Monitoring temperature-evoked Ca2+ concentration
      changes in the AIZ-RIA neural pathway revealed that starvation, a conditioning
      factor, downregulated AIZ activity through calcineurin during associative
      learning between temperature and feeding state. Our results demonstrate the
      molecular and physiological mechanisms of a simple neural circuit for calcineurin
      mediated associative learning behavior.

PMID- 16971521
TI  - Neural dynamics in monkey parietal reach region reflect context-specific
      sensorimotor transformations.
AB  - We investigated the neural dynamics of sensorimotor transformations in the
      parietal reach region (PRR) of monkeys. To dissociate sensory from motor goal
      representations, we used a memory-guided anti-reach task. The monkeys had to
      reach either to a visually instructed, memorized peripheral target position (pro
      reach) or to a diametrically opposed position (anti) while keeping central ocular
      fixation. Pro- and anti-reaches were randomly interleaved and indicated by a
      color instruction from the beginning of each trial. We analyzed spatiotemporal
      single-cell tuning and performed time-resolved population decoding to quantify
      the dynamic representation of the spatial visual cue, the reach goal, and the
      currently valid task rule (pro/anti mapping). Sensory information regarding the
      visual cue position was represented weakly during a short period of cue
      visibility. PRR predominantly encoded the reach goal from the end of the cue
      period on. The representation of the reach goal in the memory task evolves later
      for the anti- compared with pro-reaches, consistent with a 40-50 ms difference in
      reaction time between the two task rules. The task rule could be decoded before
      the appearance of the spatial cue, which indicates that abstract rule information
      is present in PRR that is independent of spatial cue or motor goal
      representations. Our findings support the hypothesis that PRR immediately
      translates current sensory information into reach movement plans, rather than
      storing the memorized cue location in the instructed-delay task. This finding
      indicates that PRR represents integrated knowledge on spatial sensory information
      combined with abstract behavioral rules to encode the desired movement goal.

PMID- 16971520
TI  - Blocking soluble tumor necrosis factor signaling with dominant-negative tumor
      necrosis factor inhibitor attenuates loss of dopaminergic neurons in models of
      Parkinson's disease.
AB  - The mechanisms that trigger or contribute to loss of dopaminergic (DA) neurons in
      Parkinson's disease (PD) remain unclear and controversial. Elevated levels of
      tumor necrosis factor (TNF) in CSF and postmortem brains of PD patients and
      animal models of PD implicate this proinflammatory cytokine in the
      pathophysiology of the disease; but a role for TNF in mediating loss of DA
      neurons in PD has not been clearly demonstrated. Here, we report that
      neutralization of soluble TNF (solTNF) in vivo with the engineered dominant
      negative TNF compound XENP345 (a PEGylated version of the TNF variant A145R/I97T)
      reduced by 50% the retrograde nigral degeneration induced by a striatal injection
      of the oxidative neurotoxin 6-hydroxydopamine (6-OHDA). XENP345 was
      neuroprotective only when infused into the nigra, not the striatum. XENP345/6
      OHDA rats displayed attenuated amphetamine-induced rotational behavior,
      indicating preservation of striatal dopamine levels. Similar protective effects
      were observed with chronic in vivo coinfusion of XENP345 with bacterial
      lipopolysaccharide (LPS) into the substantia nigra, confirming a role for solTNF
      dependent neuroinflammation in nigral degeneration. In embryonic rat midbrain
      neuron/glia cell cultures exposed to LPS, even delayed administration of XENP345
      prevented selective degeneration of DA neurons despite sustained microglia
      activation and secretion of solTNF. XENP345 also attenuated 6-OHDA-induced DA
      neuron toxicity in vitro. Collectively, our data demonstrate a role for TNF in
      vitro and in vivo in two models of PD, and raise the possibility that delaying
      the progressive degeneration of the nigrostriatal pathway in humans is
      therapeutically feasible with agents capable of blocking solTNF in early stages
      of PD.

PMID- 16971522
TI  - TRPV1 receptors in the CNS play a key role in broad-spectrum analgesia of TRPV1
      antagonists.
AB  - Vanilloid receptor type 1 (TRPV1) is a ligand-gated nonselective cation channel
      that is considered to be an important integrator of various pain stimuli such as
      endogenous lipids, capsaicin, heat, and low pH. In addition to expression in
      primary afferents, TRPV1 is also expressed in the CNS. To test the hypothesis
      that the CNS plays a differential role in the effect of TRPV1 antagonists in
      various types of pain, the analgesic effects of two TRPV1 antagonists with
      similar in vitro potency but different CNS penetration were compared in vivo.
      Oral administration of either A-784168 (1-[3-(trifluoromethyl)pyridin-2-yl]-N-[4
      (trifluoromethylsulfonyl)phenyl]-1,2,3,6-tetrahydropyridine-4-carboxamide) (good
      CNS penetration) or A-795614 (N-1H-indazol-4-yl-N'-[(1R)-5-piperidin-1-yl-2,3
      dihydro-1H-inden-1-yl]urea) (poor CNS penetration) blocked capsaicin-induced
      acute pain with the same potency. In complete Freund's adjuvant (CFA)-induced
      chronic inflammatory pain, oral administration of either compound blocked thermal
      hyperalgesia with similar potency. Furthermore, intraplantar or intrathecal
      administration of A-784168 blocked CFA-induced thermal hyperalgesia, suggesting
      that both peripheral and CNS TRPV1 receptors may play a role in inflammatory
      thermal hyperalgesia. The effects of the two TRPV1 antagonists were further
      assessed in models presumably mediated by central sensitization, including CFA-
      and capsaicin-induced mechanical allodynia and osteoarthritic pain. In these
      models, the potency of the two compounds was similar after intrathecal
      administration. However, when administered orally, A-784168, with good CNS
      penetration, was much more potent than A-795614. Together, these results
      demonstrate that TRPV1 receptors in the CNS play an important role in pain
      mediated by central sensitization. In addition, these results demonstrate that
      significant CNS penetration is necessary for a TRPV1 antagonist to produce broad
      spectrum analgesia.

PMID- 16971523
TI  - Novel agonist monoclonal antibodies activate TrkB receptors and demonstrate
      potent neurotrophic activities.
AB  - Tyrosine kinase receptor B (TrkB) mediates neurotrophic effects of brain-derived
      neurotrophic factor (BDNF) to increase neuronal survival, differentiation,
      synaptic plasticity, and neurogenesis. The therapeutic potential of TrkB
      activation using BDNF has been demonstrated well in several preclinical models of
      CNS diseases, validating TrkB as a promising drug target. Therefore, we aimed to
      develop TrkB-specific receptor agonists by using a monoclonal antibody approach.
      After generation of hybridoma clones and assessment of their binding and
      functional activity, we identified five mouse monoclonal antibodies that show
      highly selective binding to TrkB and that induce robust activation of TrkB
      signaling. Epitope mapping studies using competition analysis showed that each of
      the monoclonal antibodies recognizes a unique binding site on TrkB, some of which
      are distinct from BDNF docking sites. These antibodies behave as true agonists
      based on their ability to both activate proximal and secondary signaling
      molecules downstream of TrkB receptors and promote neuronal survival and neurite
      outgrowth. The binding affinities and the functional efficacy of these antibodies
      are comparable to those of BDNF, whereas they do not bind to the p75 low-affinity
      neurotrophin receptor at all. Therefore, they could represent novel reagents to
      explore the pathophysiological roles of TrkB and its potential therapeutic
      utility in treating CNS disorders.

PMID- 16971525
TI  - Receptor and transmitter release properties set the time course of retinal
      inhibition.
AB  - Synaptic inhibition is determined by the properties of postsynaptic receptors,
      neurotransmitter release, and clearance, but little is known about how these
      factors shape sensation-evoked inhibition. The retina is an ideal system to
      investigate inhibition because it can be activated physiologically with light,
      and separate inhibitory pathways can be assayed by recording from rod bipolar
      cells that possess distinct glycine, GABA(A), and GABA(C) receptors (R). We show
      that receptor properties differentially shape spontaneous IPSCs, whereas both
      transmitter release and receptor properties shape light-evoked (L) IPSCs.
      GABA(C)R-mediated IPSCs decayed the slowest, whereas glycineR- and GABA(A)R
      mediated IPSCs decayed more rapidly. Slow GABA(C)Rs determined the L-IPSC decay,
      whereas GABA(A)Rs and glycineRs, which mediated rapid onset responses, determined
      the start of the L-IPSC. Both fast and slow inhibitory inputs distinctly shaped
      the output of rod bipolar cells. The slow GABA(C)Rs truncated glutamate release,
      making the A17 amacrine cell L-EPSCs more transient, whereas the fast GABA(A)R
      and glycineRs reduced the initial phase of glutamate release, limiting the peak
      amplitude of the L-EPSC. Estimates of transmitter release time courses suggested
      that glycine release was more prolonged than GABA release. The time course of
      GABA release activating GABA(C)Rs was slower than that activating GABA(A)Rs,
      consistent with spillover activation of GABA(C)Rs. Thus, both postsynaptic
      receptor and transmitter release properties shape light-evoked inhibition in
      retina.

PMID- 16971524
TI  - Stromal-derived factor-1 (CXCL12) regulates laminar position of Cajal-Retzius
      cells in normal and dysplastic brains.
AB  - Normal brain development requires a series of highly complex and interrelated
      steps. This process presents many opportunities for errors to occur, which could
      result in developmental defects in the brain, clinically referred to as
      malformations of cortical development. The marginal zone and Cajal-Retzius cells
      are key players in cortical development and are established early, yet there is
      little understanding of the factors resulting in the disruption of the marginal
      zone in many types of cortical malformation syndromes. We showed previously that
      treatment with methylazoxymethanol in rats causes marginal zone dysplasia with
      displacement of Cajal-Retzius cells to deeper cortical layers. Here we establish
      that loss of activity of the chemokine stromal-derived factor-1 (SDF1) (CXCL12),
      which is expressed by the leptomeninges, is necessary and sufficient to cause
      marginal zone disorganization in this widely used teratogenic animal model. We
      also found that mice with mutations in the main receptor for SDF1 (CXCR4) have
      Cajal-Retzius cells displaced to deeper cortical layers. Furthermore, by
      inhibiting SDF1 signaling in utero by intraventricular injection of a receptor
      antagonist, we establish that SDF1 signaling is required for the maintenance of
      Cajal-Retzius cell position in the marginal zone during normal cortical
      development. Our data imply that cortical layering is not a static process, but
      rather requires input from locally produced molecular cues for maintenance, and
      that complex syndromes of cortical malformation as a result of environmental
      insults may still be amenable to explanation by interruption of specific
      molecular signaling pathways.

PMID- 16971526
TI  - Homeostatic regulation of sleep: a role for preoptic area neurons.
AB  - The median preoptic nucleus (MnPN) and the ventrolateral preoptic area (vlPOA)
      contain putative sleep-regulatory neurons that exhibit elevated discharge rates
      during sleep compared with waking. Expression of c-Fos protein immunoreactivity
      (IR) in GABAergic neurons in the MnPN and the vlPOA is high in spontaneously
      sleeping rats and in rats undergoing recovery sleep after sleep deprivation.
      However, it is unclear whether c-Fos-IR in these neurons is evoked by increases
      in sleep pressure or by increases in sleep amount. We examined c-Fos-IR in MnPN
      and vlPOA neurons under experimental conditions that dissociated homeostatic
      sleep pressure, sleep amount, and time of day. Groups of rats with strong diurnal
      rhythms in sleep-wake organization were killed after (1) spontaneous sleep in the
      light, (2) spontaneous sleep in the dark, (3) sleep deprivation (SLD) in the
      light and (4) recovery sleep after SLD in the light. Numbers of GABAergic neurons
      expressing c-Fos-IR in the MnPN were significantly higher after SLD in the light
      compared with spontaneous sleep and recovery sleep in the light. In contrast, Fos
      IR in vlPOA GABAergic neurons was most prevalent after spontaneous sleep and
      recovery sleep in the light. No light-dark differences in Fos-IR were observed in
      the MnPN after SLD in groups of rats with weak or absent diurnal sleep-waking
      rhythms. Our findings define potential roles for MnPN and vlPOA GABAergic neurons
      in homeostatic aspects of sleep regulation.

PMID- 16971527
TI  - DARPP-32 involvement in the photic pathway of the circadian system.
AB  - The multifunctional regulator of protein kinases and phosphatases dopamine- and
      cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) is an important molecular
      target of the dopamine signaling pathway. In the present study, we investigated
      the possible involvement of DARPP-32 regulation in the circadian system using
      DARPP-32 knock-out (KO) mice. These mice showed normal entrainment to a 12 h
      light/dark cycle and free run in constant darkness with a period similar to that
      of wild-type controls. After light exposure, however, the behavioral phase-delay
      response and the expression of light-induced clock gene mPer2 were attenuated in
      the DARPP-32 KO mice. Attenuated phase delays were also seen in animals bearing a
      point mutation in DARPP-32 at the PKA (Thr34) but not at the casein kinase I
      (Ser130) phosphorylation site. We next examined DARPP-32 expression in the retina
      and intergeniculate leaflet (IGL), both of which convey light information to the
      suprachiasmatic nucleus (SCN), the locus of a master circadian clock, and in the
      SCN itself. DARPP-32 was expressed in the retina but not in the IGL or the SCN.
      The results indicate that DARPP-32 is involved in the retinal pathway
      transmitting photic information that resets the circadian clock.

PMID- 16971528
TI  - Estrogen receptor protein interaction with phosphatidylinositol 3-kinase leads to
      activation of phosphorylated Akt and extracellular signal-regulated kinase 1/2 in
      the same population of cortical neurons: a unified mechanism of estrogen action.
AB  - 17Beta-estradiol (E2)-induced neuroprotection is dependent on mitogen-activated
      protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K) signaling
      cascades. We sought to determine whether E2 neuroprotective mechanisms are
      mediated by a unified signaling cascade activated by estrogen receptor (ER)-PI3K
      interaction within the same population of neurons or whether E2 activation of
      extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt are independent
      signaling events in different neuronal populations. Immunoprecipitation of E2
      treated cortical neurons was conducted to determine a protein-protein interaction
      between ER and the PI3K regulatory subunit p85. Subsequently, cortical neurons
      were treated with E2 alone or in presence of MAPK inhibitors or PI3K inhibitors.
      Results of these analyses indicated a protein-protein interaction between ER and
      p85 that was time-dependent and consistent with the temporal profile for
      generation of Akt (pAkt) and ERK1/2 phosphorylation (pERK1/2). E2-induced
      phosphorylation of Akt, was first apparent at 10 min and maximal at 30 min.
      Simultaneously, E2-induced pERK1/2 was first apparent at 5-10 min and maximal at
      30 min. Inhibition of PI3K completely blocked E2 activation of pAkt at 10 and 30
      min and blocked E2 activation of ERK1/2 at 10 min, which revealed a PI3K
      independent activation of ERK at 30 min. Double immunocytochemical labeling for
      pERK1/2 and pAkt demonstrated that E2 induced both signaling pathways in the same
      neurons. These results indicate a unified signaling mechanism for rapid E2 action
      that leads to the coordinated activation of both pERK1/2 and pAkt in the same
      population of neurons. Implications of these results for understanding estrogen
      mechanism of action in neurons and therapeutic development are considered.

PMID- 16971529
TI  - Endothelial proliferation and increased blood-brain barrier permeability in the
      basal ganglia in a rat model of 3,4-dihydroxyphenyl-L-alanine-induced dyskinesia.
AB  - 3,4-Dihydroxyphenyl-L-alanine (L-DOPA)-induced dyskinesia is associated with
      molecular and synaptic plasticity in the basal ganglia, but the occurrence of
      structural remodeling through cell genesis has not been explored. In this study,
      rats with 6-hydroxydopamine lesions received injections of the thymidine analog 5
      bromo-2'-deoxyuridine (BrdU) concomitantly with L-DOPA for 2 weeks. A large
      number of BrdU-positive cells were found in the striatum and its output
      structures (globus pallidus, entopeduncular nucleus, and substantia nigra pars
      reticulata) in L-DOPA-treated rats that had developed dyskinesia. The vast
      majority (60-80%) of the newborn cells stained positively for endothelial
      markers. This endothelial proliferation was associated with an upregulation of
      immature endothelial markers (nestin) and a downregulation of endothelial barrier
      antigen on blood vessel walls. In addition, dyskinetic rats exhibited a
      significant increase in total blood vessel length and a visible extravasation of
      serum albumin in the two structures in which endothelial proliferation was most
      pronounced (substantia nigra pars reticulata and entopeduncular nucleus). The
      present study provides the first evidence of angiogenesis and blood-brain barrier
      dysfunction in an experimental model of L-DOPA-induced dyskinesia. These
      microvascular changes are likely to affect the kinetics of L-DOPA entry into the
      brain, favoring the occurrence of motor complications.

PMID- 16971530
TI  - Activated c-Jun N-terminal kinase is required for axon formation.
AB  - A critical transition in neuron development is formation of the axon, which
      establishes the polarized structure of the neuron that underlies its entire input
      and output capabilities. The morphological events that occur during axonogenesis
      have long been known, yet the molecular determinants underlying axonogenesis
      remain poorly understood. We demonstrate here that axonogenesis requires
      activated c-Jun N-terminal kinase (JNK). JNK is expressed throughout the neuron,
      but its phosphorylated, activated form is highly enriched in the axon. In young
      axons, activated JNK forms a proximodistal gradient of increasing intensity,
      beginning at about the point where the axon exceeds the lengths of the other
      neurites (minor processes). Treatment with SP600125, a specific inhibitor of JNK,
      reversibly inhibits axonogenesis but does not prevent the formation of minor
      processes or their differentiation into dendrites (based on their immunostaining
      with marker proteins). Expression of a dominant-negative construct against JNK
      similarly prevents axonogenesis. Investigation of JNK targets revealed that
      activating transcription factor-2 is phosphorylated under normal conditions in
      neurons, and its phosphorylation is significantly attenuated after JNK
      inhibition. These results demonstrate that activated JNK is required for
      axonogenesis but not formation of minor processes or development of dendrites.

PMID- 16971531
TI  - The transcriptional activator hypoxia inducible factor 2 (HIF-2/EPAS-1) regulates
      the oxygen-dependent expression of erythropoietin in cortical astrocytes.
AB  - In the ischemic or hypoxic brain, astrocytes appear to be one of the main sources
      of erythropoietin (EPO). In this study, we investigated the differential
      contribution of hypoxia inducible factor (HIF) isoforms to the regulation of
      hypoxic EPO expression in cultured astrocytes. In addition, using an in vitro
      model of oxygen-glucose deprivation (OGD), we studied the role of HIF-1alpha and
      HIF-2alpha in the generation of paracrine protective signals by astrocytes that
      modulate the survival of neurons exposed to OGD. Expression of HIF-1alpha or HIF
      2alpha was abrogated by infecting astrocytes with lentiviral particles encoding
      small interference RNA specific for HIF-1alpha or HIF-2alpha (siHIF-1alpha or
      siHIF-2alpha). Astrocytes infected with siHIF-1alpha showed abrogated hypoxic
      induction of vascular endothelial growth factor (VEGF) and lactate dehydrogenase
      (LDH) but normal EPO induction. In contrast, reduction of HIF-2alpha expression
      by siHIF-2alpha led to a drastic decrease of EPO hypoxic expression, but it did
      not affect LDH or VEGF upregulation. To further test whether HIF-2 is sufficient
      to drive EPO upregulation, we expressed oxygen-insensitive mutant forms of HIF
      1alpha (mtHIF-1alpha) (P402A/P577A) and HIF-2alpha (mtHIF-2alpha) (P405A/P530A).
      Expression of mtHIF-2alpha but not mtHIF-1alpha in normoxic astrocytes resulted
      in a significant upregulation of EPO mRNA and protein. Accordingly, HIF-2alpha
      but not HIF-1alpha was found to be associated with the EPO hypoxia-response
      element by a chromatin immunoprecipitation assay. Interestingly, conditioned
      medium from astrocytes challenged by sublethal OGD improved neuronal survival to
      OGD; however, this effect was abolished during the downregulation of astrocytic
      HIF-2alpha using siHIF-2alpha. These results indicate that HIF-2alpha mediates
      the transcriptional activation of EPO expression in astrocytes, and this pathway
      may promote astrocytic paracrine-dependent neuronal survival during ischemia.

PMID- 16971532
TI  - Expression of multiple P2X receptors by glossopharyngeal neurons projecting to
      rat carotid body O2-chemoreceptors: role in nitric oxide-mediated efferent
      inhibition.
AB  - In mammals, ventilation is peripherally controlled by the carotid body (CB),
      which receives afferent innervation from the petrosal ganglion and efferent
      innervation from neurons located along the glossopharyngeal nerve (GPN). GPN
      neurons give rise to the "efferent inhibitory" pathway via a plexus of neuronal
      nitric oxide (NO) synthase-positive fibers, believed to be responsible for CB
      chemoreceptor inhibition via NO release. Although NO is elevated during natural
      CB stimulation by hypoxia, the underlying mechanisms are unclear. We hypothesized
      that ATP, released by rat CB chemoreceptors (type 1 cells) and/or red blood cells
      during hypoxia, may directly activate GPN neurons and contribute to NO-mediated
      inhibition. Using combined electrophysiological, molecular, and confocal
      immunofluorescence techniques, we detected the expression of multiple P2X
      receptors in GPN neurons. These receptors involve at least four different
      purinergic subunits: P2X2 [and the splice variant P2X2(b)], P2X3, P2X4, and P2X7.
      Using a novel coculture preparation of CB type I cell clusters and GPN neurons,
      we tested the role of P2X signaling on CB function. In cocultures, fast
      application of ATP, or its synthetic analog 2',3'-O-(4 benzoylbenzoyl)-ATP,
      caused type I cell hyperpolarization that was prevented in the presence of the NO
      scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide
      potassium. These data suggest that ATP released during hypoxic stress from CB
      chemoreceptors (and/or red blood cells) will cause GPN neuron depolarization
      mediated by multiple P2X receptors. Activation of this pathway will lead to
      calcium influx and efferent inhibition of CB chemoreceptors via NO synthesis and
      consequent release.

PMID- 16971533
TI  - Alpha-band electroencephalographic activity over occipital cortex indexes
      visuospatial attention bias and predicts visual target detection.
AB  - Covertly directing visual attention toward a spatial location in the absence of
      visual stimulation enhances future visual processing at the attended position.
      The neuronal correlates of these attention shifts involve modulation of neuronal
      "baseline" activity in early visual areas, presumably through top-down control
      from higher-order attentional systems. We used electroencephalography to study
      the largely unknown relationship between these neuronal modulations and
      behavioral outcome in an attention orienting paradigm. Covert visuospatial
      attention shifts to either a left or right peripheral position in the absence of
      visual stimulation resulted in differential modulations of oscillatory alpha-band
      (8-14 Hz) activity over left versus right posterior sites. These changes were
      driven by varying degrees of alpha-decreases being maximal contralateral to the
      attended position. When expressed as a lateralization index, these alpha-changes
      differed significantly between attention conditions, with negative values
      (alpha_right < alpha_left) indexing leftward and more positive values (alpha_left
      < or = alpha_right) indexing rightward attention. Moreover, this index appeared
      deterministic for processing of forthcoming visual targets. Collapsed over
      trials, there was an advantage for left target processing in accordance with an
      overall negative bias in alpha-index values. Across trials, left targets were
      detected most rapidly when preceded by negative index values. Detection of right
      targets was fastest in trials with most positive values. Our data indicate that
      collateral modulations of posterior alpha-activity, the momentary bias of
      visuospatial attention, and imminent visual processing are linked. They suggest
      that the momentary direction of attention, predicting spatial biases in imminent
      visual processing, can be estimated from a lateralization index of posterior
      alpha-activity.

PMID- 16971534
TI  - Context-dependent human extinction memory is mediated by a ventromedial
      prefrontal and hippocampal network.
AB  - In fear extinction, an animal learns that a conditioned stimulus (CS) no longer
      predicts a noxious stimulus [unconditioned stimulus (UCS)] to which it had
      previously been associated, leading to inhibition of the conditioned response
      (CR). Extinction creates a new CS-noUCS memory trace, competing with the initial
      fear (CS-UCS) memory. Recall of extinction memory and, hence, CR inhibition at
      later CS encounters is facilitated by contextual stimuli present during
      extinction training. In line with theoretical predictions derived from animal
      studies, we show that, after extinction, a CS-evoked engagement of human
      ventromedial prefrontal cortex (VMPFC) and hippocampus is context dependent,
      being expressed in an extinction, but not a conditioning, context. Likewise, a
      positive correlation between VMPFC and hippocampal activity is extinction context
      dependent. Thus, a VMPFC-hippocampal network provides for context-dependent
      recall of human extinction memory, consistent with a view that hippocampus
      confers context dependence on VMPFC.

PMID- 16971535
TI  - Suppressor of cytokine signaling-3 suppresses the ability of activated signal
      transducer and activator of transcription-3 to stimulate neurite growth in rat
      primary sensory neurons.
AB  - The actions of the neuropoietic cytokines are mediated by the gp130 receptor,
      which activates several signaling molecules including the transcription factor
      STAT3 (signal transducer and activator of transcription), which, in turn, is
      subject to feedback inhibition by SOCS3 (suppressor of cytokine signaling).
      Activation of the gp130 receptor has been implicated in axonal growth
      particularly during regeneration, but the specific contribution of STAT3 is the
      subject of conflicting reports. Measurements of SOCS3 mRNA in rat dorsal root
      ganglia showed a significant induction in this inhibitory molecule after
      peripheral nerve injury. The functions of STAT3 and SOCS3 in adult rat primary
      sensory neurons were investigated in vitro through transduction of lentiviruses
      yielding a conditionally activated STAT3, native SOCS3, or a mutant SOCS3 with
      dominant-negative actions. The SOCS3 construct was effective in inhibiting
      tyrosine phosphorylation of STAT3 in a neuroblastoma cell line and in blocking
      nuclear accumulation of endogenous STAT3 or of the conditionally activated STAT3
      chimera in primary sensory neurons. In such neurons, transduction and activation
      of STAT3 enhanced neurite growth, transduction with SOCS3 reduced neurite
      outgrowth, and transduction with mutant SOCS3 enhanced neurite growth, at least
      under basal conditions. In conclusion, STAT3 signaling is beneficial to axonal
      growth through activating transcription of unidentified genes, and SOCS3 is
      detrimental to axonal growth through inhibition of STAT3 and/or other
      transcription factors.

PMID- 16971536
TI  - Paradoxical facilitation of object recognition memory after infusion of
      scopolamine into perirhinal cortex: implications for cholinergic system function.
AB  - The cholinergic system has long been implicated in learning and memory, yet its
      specific function remains unclear. In the present study, we investigated the role
      of cortical acetylcholine in a rodent model of declarative memory by infusing the
      cholinergic muscarinic receptor antagonist scopolamine into the rat perirhinal
      cortex during different stages (encoding, storage/consolidation, and retrieval)
      of the spontaneous object recognition task. Presample infusions of scopolamine
      significantly impaired object recognition compared with performance of the same
      group of rats on saline trials; this result is consistent with previous reports
      supporting a role for perirhinal acetylcholine in object information acquisition.
      Scopolamine infusions directly before the retrieval stage had no discernible
      effect on object recognition. However, postsample infusions of scopolamine with
      sample-to-infusion delays of up to 20 h significantly facilitated performance
      relative to postsample saline infusion trials. Additional analysis suggested that
      the infusion episode could cause retroactive or proactive interference with the
      sample object trace and that scopolamine blocked the acquisition of this
      interfering information, thereby facilitating recognition memory. This is, to our
      knowledge, the first example of improved recognition memory after administration
      of scopolamine. The overall pattern of results is inconsistent with a direct role
      for cortical acetylcholine in declarative memory consolidation or retrieval.
      Rather, the cholinergic input to the perirhinal cortex may facilitate acquisition
      by enhancing the cortical processing of incoming stimulus information.

PMID- 16971537
TI  - Dissociable systems for gain- and loss-related value predictions and errors of
      prediction in the human brain.
AB  - Midbrain dopaminergic neurons projecting to the ventral striatum code for reward
      magnitude and probability during reward anticipation and then indicate the
      difference between actual and predicted outcome. It has been questioned whether
      such a common system for the prediction and evaluation of reward exists in
      humans. Using functional magnetic resonance imaging and a guessing task in two
      large cohorts, we are able to confirm ventral striatal responses coding both
      reward probability and magnitude during anticipation, permitting the local
      computation of expected value (EV). However, the ventral striatum only
      represented the gain-related part of EV (EV+). At reward delivery, the same area
      shows a reward probability and magnitude-dependent prediction error signal, best
      modeled as the difference between actual outcome and EV+. In contrast, loss
      related expected value (EV-) and the associated prediction error was represented
      in the amygdala. Thus, the ventral striatum and the amygdala distinctively
      process the value of a prediction and subsequently compute a prediction error for
      gains and losses, respectively. Therefore, a homeostatic balance of both systems
      might be important for generating adequate expectations under uncertainty.
      Prevalence of either part might render expectations more positive or negative,
      which could contribute to the pathophysiology of mood disorders like major
      depression.

PMID- 16971538
TI  - Layer-specific touch-dependent facilitation and depression in the somatosensory
      cortex during active whisking.
AB  - Brains adapt to new situations by retuning their neurons. The most common form of
      neuronal adaptation, typically observed with repetitive stimulations of passive
      sensory organs, is depression (responses gradually decrease until stabilized). We
      studied cortical adaptation when stimuli are acquired by active movements of the
      sensory organ. In anesthetized rats, artificial whisking was induced at 5 Hz, and
      activity of individual neurons in layers 2-5 was recorded during whisking in air
      (Whisking condition) and whisking against an object (Touch condition). Response
      strengths were assessed by spike counts. Input-layer responses (layers 4 and 5a)
      usually facilitated during the whisking train, whereas superficial responses
      (layer 2/3) usually depressed. In layers 2/3 and 4, but not 5a, responses were
      usually stronger during touch trials than during whisking in air. Facilitations
      were specific to the protraction phase; during retraction, responses depressed in
      all layers and conditions. These dynamic processes were accompanied by a slow
      positive wave of activity progressing from superficial to deeper layers and
      lasting for approximately 1 s, during the transient phase of response. Our
      results indicate that, in the cortex, adaptation does not depend only on the
      level of activity or the frequency of its repetition but rather on the nature of
      the sensory information that is conveyed by that activity and on the processing
      layer. The input and laminar specificities observed here are consistent with the
      hypothesis that the paralemniscal layer 5a is involved in the processing of
      whisker motion, whereas the lemniscal barrels in layer 4 are involved in the
      processing of object identity.

PMID- 16971539
TI  - Odorant deprivation reversibly modulates transsynaptic changes in the NR2B
      mediated CREB pathway in mouse piriform cortex.
AB  - The olfactory system is an outstanding model for understanding activity-dependent
      neuronal plasticity in mammals. Olfactory sensory neurons (OSNs) in the periphery
      project onto mitral/tufted cells in the olfactory bulb (OB) and these
      mitral/tufted cells in turn project to piriform cortex (PC). Numerous studies
      have examined changes in OB after a permanent OSN ablation, but little is known
      about "trans-transsynaptic" changes taking place in the PC. Permanent zinc
      sulfate lesion of the olfactory epithelium resulted in a selective loss of the
      NMDA receptor NR2B protein and mRNA expression in pyramidal cells in layer IIb of
      PC after 2-7 d. Regulatory elements affected by NR2B signaling, namely the
      phosphorylation of CREB, were also downregulated only in layer IIb neurons. These
      changes could be caused by OSN axon loss in the zinc sulfate lesion, or to a
      reduced activity. To test this hypothesis, we performed both permanent and
      reversible naris occlusion, which blocks odorant access to the nasal cavities and
      OSN activity. The expression of NR2B and phospho-CREB were downregulated 5 d
      after occlusion and this reduction was fully restored 10 d after reopening of the
      naris. Subsequently, we identified the subset of pyramidal cells in layer IIb
      that are especially sensitive to the loss of odor-evoked activity using double
      retrograde tracers. In summary, the present study provides an initial
      characterization of the molecular mechanisms associated with odor stimulation on
      second order neuronal plasticity and phenotype in the olfactory system.

PMID- 16971540
TI  - Postreactivation glucocorticoids impair recall of established fear memory.
AB  - Pavlovian fear conditioning provides one of the best rodent models of acquired
      anxiety disorders, including posttraumatic stress disorder. Injection of a
      variety of drugs after training in fear-conditioning paradigms can impair
      consolidation of fear memories. Indeed, early clinical trials suggest that
      immediate administration of such drugs after a traumatic event may decrease the
      risk of developing posttraumatic stress disorder in humans (Pitman et al., 2002;
      Vaiva et al., 2003). The use of such a treatment is limited by the difficulty of
      treating every patient at risk and by the difficulty in predicting which patients
      will experience chronic adverse consequences. Recent clinical trials suggest that
      administration of glucocorticoids may have a beneficial effect on established
      posttraumatic stress disorder (Aerni et al., 2004) and specific phobia (Soravia
      et al., 2006). Conversely, glucocorticoid administration after training is known
      to enhance memory consolidation (McGaugh and Roozendaal, 2002; Roozendaal, 2002).
      From a clinical perspective, enhancement of a fear memory or a reactivated fear
      memory would not be desirable. We report here that when glucocorticoids are
      administered immediately after reactivation of a contextual fear memory,
      subsequent recall is significantly diminished. Additional experiments support the
      interpretation that glucocorticoids not only decrease fear memory retrieval but,
      in addition, augment consolidation of fear memory extinction rather than
      decreasing reconsolidation. These findings provide a rodent model for a potential
      treatment of established acquired anxiety disorders in humans, as suggested by
      others (Aerni et al., 2004; Schelling et al., 2004), based on a mechanism of
      enhanced extinction.

PMID- 16971541
TI  - Macaque V2 neurons, but not V1 neurons, show choice-related activity.
AB  - In the macaque extrastriate cortex, robust correlations between perceptual choice
      and neuronal response have been demonstrated, frequently quantified as choice
      probabilities (CPs). Such correlations are modest in early visual cortex,
      suggesting that CPs may depend on the position of a neuron in the hierarchy of
      visual processing. However, previous studies have not compared neurons with
      similar precision in equivalent tasks. We investigated the role of cortical
      hierarchy on CP using a task for which significant CPs have been described
      previously for middle temporal area (MT). We measured CPs in disparity-selective
      neurons from both V1 and V2. The stimulus was a dynamic random dot stereogram,
      presented with a near or a far disparity, masked by varying numbers of
      binocularly uncorrelated dots. Two macaque monkeys reported whether they
      perceived a circular patch in front or behind a surrounding annulus in a forced
      choice task. For V2 (n = 69), CP was on average 0.56, the first demonstration of
      systematic CPs in a visual area as early as V2. In V1 (n = 74), average CP was at
      chance level (0.51). The pattern was similar in a subgroup of neurons selected
      such that the statistical precision in the task was on average identical to that
      reported for MT (mean CP, 0.51 for V1, n = 33; 0.58 for V2, n = 54). This
      difference between V1 and V2 could not be explained by eye movements, stimulus
      size relative to the receptive field, or differences in disparity tuning. Rather,
      it seems to reflect a functional difference (at least in disparity processing)
      between striate and extrastriate cortex.

PMID- 16971542
TI  - Regulation of store-operated calcium entry by calcium-independent phospholipase
      A2 in rat cerebellar astrocytes.
AB  - We have studied store-operated Ca2+ entry (SOCE) in Bergmann glia and granule
      cell layer astrocytes in acute brain slices of the rat cerebellum, using the Ca2+
      sensitive fluorescent dye Fluo-4 and confocal laser scanning microscopy.
      Astrocytes were identified by their morphology, location, and their Ca2+ response
      in K+-free solution. Depletion of Ca2+ stores by cyclopiazonic acid (CPA) (20
      microM) induced SOCE in both types of astrocyte. A similar Ca2+ influx was
      elicited by the calmodulin antagonist calmidazolium (CMZ) (1 microM). The SOCE
      channel blocker 2-aminoethoxy-diphenylborate (2-APB) (100 microM) and the Ca2+
      release-activated channel blocker 3,5-bistrifluoromethyl pyrazole derivative
      (BTP2) (20 microM) suppressed the CPA- and the CMZ-induced Ca2+ influx.
      Pretreatment of acute slices with the specific Ca2+-independent phospholipase A2
      (iPLA2) inhibitor bromoenol lactone (BEL) (25 microM) blocked the CPA- and the
      CMZ-induced Ca2+ influx. The lysophospholipid products of iPLA2,
      lysophosphatidylcholine (250 nM) and lysophosphatidylinositol (250 nM), but not
      lysophosphatidic acid (250 nM), induced a BTP2- and 2-APB-sensitive, but BEL
      insensitive, Ca2+ influx. CPA or CMZ enhanced the BEL-sensitive enzymatic
      activity of iPLA2 in cerebellar astrocyte culture. Inhibition of iPLA2 expression
      by specific antisense oligodeoxynucleotide of iPLA2 reduced the SOCE and the Ca2+
      store refilling in cultured astrocytes. Spontaneous Ca2+ oscillations in
      astrocytes in situ were reduced after inhibiting SOCE channels or iPLA2 activity.
      The results suggest that the depletion of Ca2+ stores activates iPLA2 to open
      Ca2+ channels in the plasma membrane by the formation of lysophospholipids in
      astrocytes, presumably to refill the stores and allow normal Ca2+ signaling.

PMID- 16971543
TI  - High levels of Cre expression in neuronal progenitors cause defects in brain
      development leading to microencephaly and hydrocephaly.
AB  - Hydrocephalus is a common and variegated pathology often emerging in newborn
      children after genotoxic insults during pregnancy (Hicks and D'Amato, 1980). Cre
      recombinase is known to have possible toxic effects that can compromise normal
      cell cycle and survival. Here we show, by using three independent nestin Cre
      transgenic lines, that high levels of Cre recombinase expression into the nucleus
      of neuronal progenitors can compromise normal brain development. The transgenics
      analyzed are the nestin Cre Balancer (Bal1) line, expressing the Cre recombinase
      with a nuclear localization signal, and two nestin CreER(T2) (Cre recombinase
      fused with a truncated estrogen receptor) mice lines with different levels of
      expression of a hybrid CreER(T2) recombinase that translocates into the nucleus
      after tamoxifen treatment. All homozygous Bal1 nestin Cre embryos displayed
      reduced neuronal proliferation, increased aneuploidy and cell death, as well as
      defects in ependymal lining and lamination of the cortex, leading to
      microencephaly and to a form of communicating hydrocephalus. An essentially
      overlapping phenotype was observed in the two nestin CreER(T2) transgenic lines
      after tamoxifen mediated-CreER(T2) translocation into the nucleus. Neither
      tamoxifen-treated wild-type nor nestin CreER(T2) oil-treated control mice
      displayed these defects. These results indicate that some forms of hydrocephalus
      may derive from a defect in neuronal precursors proliferation. Furthermore, they
      underscore the potential risks for developmental studies of high levels of
      nuclear Cre in neurogenic cells.

PMID- 16971544
TI  - Whose deaths matter? Mortality, advocacy, and attention to disease in the mass
      media.
AB  - Diseases capture public attention in varied ways and to varying degrees. In this
      essay, we use a unique data set that we have collected about print and broadcast
      media attention to seven diseases across nineteen years in order to address two
      questions. First, how (if at all) is mortality related to attention? Second, how
      (if at all) is advocacy, in the form of organized interest group activity,
      related to media attention? Our analysis of the cross-disease and cross-temporal
      variation in media attention suggests that who suffers from a disease as well as
      how many suffer are critical factors in explaining why some diseases get more
      attention than others. In particular, our data reveal that both the print and the
      broadcast media tend to be much less attentive to diseases that
      disproportionately burden blacks relative to whites. We also find a positive link
      between the size of organizational communities that take an interest in disease
      and media attention, though this finding depends on the characteristics of those
      communities. Finally, this study also reveals the limitations of relying on
      single-disease case studies-and particularly HIV/AIDS-to understand how and why
      disease captures public attention. Many previous inferences about media attention
      that have been drawn from the case of AIDS are not reflective of the attention
      allocated to other diseases.

PMID- 16971545
TI  - Is a public reporting approach appropriate for nursing home care?
AB  - Publicizing quality information has been used as a quality improvement strategy
      in the acute care sector for more than a decade. Despite research showing mixed
      results of these efforts, publicly reporting quality measures is currently being
      pursued as a quality improvement strategy for nursing homes. Designed to empower
      consumers to make informed choices and to stimulate provider competition on
      quality, nursing home public reporting began in 1998 with the Nursing Home
      Compare Web site and has received greater emphasis in the 2002 Nursing Home
      Quality Initiative, both directed by the federal government. Focusing on the
      response of three key stakeholder groups across settings of care-consumers,
      providers, and purchasers-I identify several challenges that nursing home
      reporting must overcome to be successful. I conclude that publicly reporting
      quality measures for nursing homes will have a harder time promoting quality
      improvement than for acute care settings, where results have been disappointing
      thus far. In addition to the conceptual analysis, I evaluate whether the quality
      information reported on Nursing Home Compare had any impact on nursing home
      occupancy rates following its release. Using a pre/post-release design, I find
      that the effect of public reporting on nursing home occupancy rates has been
      minimal thus far. Although some estimates of effect are statistically significant
      and in the hypothesized direction, they all suggest very small effect sizes. It
      is unclear whether the absence of a larger reporting effect to date is specific
      to Nursing Home Compare or whether it inheres to the broader task of using
      quality information to promote change in the nursing home care sector.

PMID- 16971546
TI  - The promise and limits of racial/ethnic concordance in physician-patient
      interaction.
AB  - Although some scholars suggest that racial/ethnic concordance between physicians
      and patients will do much to eliminate disparities in medical care, the evidence
      for concordance effects is mixed. Using nationally representative data with an
      oversample of blacks and Latinos, this study examines a variety of topics,
      including beliefs about and preferences for concordance, the effects of
      concordance on patient experiences, and interactions between expectations and
      experiences. The results point to the limited effects of concordance in general
      but illuminate for whom concordance matters most. The results encourage more
      nuanced and contingent theories. They suggest that racial/ethnic concordance
      holds little salience in the minds of most black and Latino patients and that
      discordance has little effect. Nevertheless, there is some evidence that
      concordance has a positive effect among those who prefer concordance-thus the
      apparent effects of concordance might reflect the effects of patient choice more
      than concordance per se. The conclusion sketches policy implications, including
      the merits of promoting concordance among targeted groups of patients, even in
      the absence of overall effects on disparities.

PMID- 16971553
TI  - Conformational constraining of inactive and active States of a seven
      transmembrane receptor by metal ion site engineering in the extracellular end of
      transmembrane segment V.
AB  - The extracellular part of transmembrane segment V (TM-V) is expected to be
      involved in the activation process of 7TM receptors, but its role is far from
      clear. Here, we study the highly constitutively active CXC-chemokine receptor
      encoded by human herpesvirus 8 (ORF74-HHV8), in which a metal ion site was
      introduced at the extracellular end of TM-V by substitution of two arginines at
      positions V:01 and V:05 with histidines [R208H; R212H]. The metal ion site
      conferred high-potency inverse agonist properties (EC(50), 1.7 microM) to Zn(II)
      in addition to agonist and allosteric enhancing properties at concentrations >10
      microM. The chemokine interaction with [R208H;R212H]-ORF74 was altered compared
      with wild-type ORF74-HHV8 with decreased agonist (CXCL1/GROalpha) potency (84
      fold), affinity (5.8- and 136-fold in competition against agonist and inverse
      agonist, respectively), and binding capacity (B(max); 25-fold). Zn(II) in
      activating concentrations (100 microM) acted as an allosteric enhancer as it
      increased the B(max) (7.1-fold), the potency (9.9-fold), the affinity (1.7- and
      6.1-fold in competition against agonist and inverse agonist, respectively), and
      the efficacy (2.5-fold) of CXCL1/GROalpha. The activating properties of Zn(II)
      were not due to a metal ion site between the ligand and the receptor because
      CXCL1/GROalpha analogs in which the putative metal-ion binding residues had been
      substituted-[H19A] and [H34A]-acted like wild-type CXCL1/GROalpha. Based on the
      complex action of Zn(II) and on the chemokine interaction for [R208H;R212H]
      ORF74, we conclude that the extracellular end of TM-V is important for the
      activation of this CXC-chemokine receptor.

PMID- 16971554
TI  - 2,3,7,8-tetrachlorodibenzo-p-dioxin and epidermal growth factor cooperatively
      suppress peroxisome proliferator-activated receptor-gamma1 stimulation and
      restore focal adhesion complexes during adipogenesis: selective contributions of
      Src, Rho, and Erk distinguish these overlapping processes in C3H10T1/2 cells.
AB  - Stimulation of PPARgamma1 and adipogenesis in multipotential C3H10T1/2 cells by
      the combination of dexamethasone and 3-isobutyl-1-methylxanthine (DM) is
      suppressed by 2,3,7,8 tetrachlorodibenzodioxin (TCDD) (10 nM). This suppression
      requires sustained activation of extracellular signal-regulated kinase (Erk)1/2.
      We show that it arises from an effect of TCDD on epidermal growth factor (EGF)
      signaling. DM initiates an early loss of cell adhesion that is reversed by this
      TCDD/EGF synergy. Src kinase activity was completely essential for adhesion
      restoration, sustained Erk activation, and suppression of peroxisome proliferator
      activated receptor (PPAR)gamma1. MEK/Erk activity did not contribute, however, to
      TCDD-induced adhesion. Stimulation of adhesion may therefore precede elevation of
      Erk. Adhesion is produced by interaction of alphabeta integrins with
      extracellular matrix proteins and subsequent Src-mediated phosphorylation of
      focal adhesion kinase (FAK, Tyr576/577) and paxillin (Tyr118). TCDD enhanced the
      steady state Src-mediated phosphorylation of FAK but not of paxillin. Protein
      tyrosine phosphatase (PTPase) inhibition by orthovanadate (OVA) showed that this
      Src activity is highly restricted by PTPases. Partial inhibition of PTPases by
      OVA mimicked TCDD in producing EGF- and Src-dependent effects on cell adhesion
      and PPARgamma1 suppression. TCDD may therefore induce a protein that enhances Src
      effectiveness at adhesion sites. Rho kinase (ROCK) inhibition blocked TCDD/EGF
      stimulation of clustered focal adhesion complexes without affecting either
      sustained Erk activation or suppression of PPARgamma1. Thus, this ROCK-mediated
      clustering of integrin complexes is not needed for the effects of TCDD on Erk and
      PPARgamma1. A minimal cholesterol depletion with beta-methylcyclodextrin
      attenuated TCDD effects on PPARgamma1 and Erk activation. TCDD intervention is
      therefore linked to extracellular proteins. It indicates that TCDD-enhanced
      stimulation of EGF signaling to Erk may derive from the initial alphabeta
      integrin complexes.

PMID- 16971555
TI  - Primary immunodeficiency syndromes associated with defective DNA double-strand
      break repair.
AB  - Damaging DNA double-strand breaks (DNA-DSBs) following ionizing radiation (IR)
      exposure, potentially lead to cell death or carcinogenesis. Non-homologous end
      joining (NHEJ) is the main repair pathway employed by vertebrate cells to repair
      such damage. Many repair pathway proteins have been identified. The creation of
      many diverse lymphocyte receptors to identify potential pathogens has evolved by
      breaking and randomly re-sorting the gene segments coding for antigen receptors.
      Subsequent DNA-DSB repair utilizes the NHEJ proteins. Individuals with defective
      repair pathways are increasingly recognized with radiosensitivity and
      immunodeficiency. Patients with defects in ataxia-telangiectasia mutated, nibrin,
      MRE11, Rad50, Artemis, DNA ligase IV and Cernunnos-XRCC4-like factor have been
      identified. Most exhibit immunodeficiency, with a spectrum of presentation and
      overlap between conditions. Conventional treatment with immunoglobulin
      replacement or haematopoietic stem cell transplantation (HSCT) can be effective.
      A greater understanding of the molecular defect will enable better, tailored
      therapies to improve survival.

PMID- 16971556
TI  - The expression of multiple connexins throughout spermatogenesis in the rainbow
      trout testis suggests a role for complex intercellular communication.
AB  - Certain fish, such as rainbow trout (Oncorhynchus mykiss), are seasonal breeders.
      Spermatogenesis in rainbow trout is synchronous; therefore, at any time point
      during this process, germ cells are predominantly at the same stage of
      development. As such, rainbow trout represent an excellent model in which to
      study spermatogenesis. Gap junctions are composed of connexons, which are
      themselves formed by six transmembrane proteins termed connexins (Cxs). The
      objectives of this study were to assess which Cxs are expressed in the rainbow
      trout testis, and if their expression was stage specific during gonadal
      maturation. Rainbow trout were killed at various stages of maturation, and total
      cellular RNA was isolated from the testes. RT-PCR using degenerate primers
      recognizing all vertebrate Cxs indicates that there are several different Cxs in
      trout testes. Amplicons were cloned and sequenced. Homology comparisons indicate
      that these were cx43, cx43.4, cx31, and cx30. Immunolocalization of these Cxs
      indicate that Cx43 was localized primarily to Sertoli cells, while Cx43.4 was
      localized along the lateral plasma membranes between adjacent spermatocytes. Cx30
      was localized to the interstitial Leydig cells, and Cx31 was localized primarily
      to the endothelium of interstitial blood vessels. The expression of each Cx
      varied as a function of the stage of spermatogenesis, suggesting that the
      expression of these proteins is highly regulated. Together, these results
      indicate that intercellular communication in the testis is complex, involves
      several different Cxs, and is a highly regulated process.

PMID- 16971557
TI  - The expression of prostaglandin endoperoxide synthase 2 messenger RNA and the
      proportion of smooth muscle and collagen in the sheep cervix during the estrous
      cycle.
AB  - The use of transcervical artificial insemination in sheep is limited because of
      the anatomy of the cervix, which restricts the passage of an inseminating pipette
      into the uterine lumen. There is a degree of natural cervical relaxation at
      estrus that enables greater penetration with an inseminating pipette. We
      hypothesize that this relaxation may be regulated by cervical prostaglandin
      synthesis and remodeling of the cervical extracellular matrix. The present study
      investigated the changes in prostaglandin endoperoxide synthase 2 (PTGS2) mRNA
      expression and the proportion of smooth muscle and collagen in the sheep cervix
      during the estrous cycle. Sheep cervices were collected at four stages of the
      estrous cycle: prior to the LH surge, during the LH surge, after the LH surge,
      and during the luteal phase. The expression of cervical PTGS2 mRNA was determined
      by in situ hybridization, and the proportion of smooth muscle and collagen in the
      cervix was investigated by Masson trichrome staining. The expression of PTGS2
      mRNA in the sheep cervix was greatest prior to the LH surge, when estradiol
      concentrations were also greatest. The increase in PTGS2 mRNA expression was
      associated with an increase in the proportion of collagen in the sheep cervix. We
      propose that prior to the LH surge, estradiol may stimulate PTGS2 mRNA expression
      and hence prostaglandin E2 synthesis in the sheep cervix to regulate cervical
      relaxation, most likely through the rearrangement of collagen bundles within the
      cervical extracellular matrix.

PMID- 16971558
TI  - Adrenomedullin 2 antagonist infusion to rats during midgestation causes
      fetoplacental growth restriction through apoptosis.
AB  - Adrenomedullin 2 (ADM2) is a recently discovered member of the
      calcitonin/calcitonin gene-related peptide family with an exon-intron structure
      similar to that of ADM. The mRNA of ADM2 is expressed in several tissues,
      including uterus and ovary. The present study was designed to assess the effects
      of ADM2 antagonist (ADM2(17-47)) infusion to pregnant rats on fetal and placental
      growth. On Day 15 of gestation, rats were implanted s.c. with osmotic minipumps
      delivering 50 and 200 mug per rat per day of ADM2(17-47) and were killed on
      Gestational Day 18. In ADM2(17-47)-treated rats, placental weights were
      significantly inhibited in a dose-related manner, with an 11% reduction in the
      group of rats receiving 200 microg/day, whereas the fetal weights were reduced by
      17% without significant differences between the two doses. 2 In ADM2(17-47)
      infused rats, increased apoptosis was demonstrated in the labyrinth and
      junctional zones of rat placenta by the TUNEL method compared with the control
      animals. Western blot analysis demonstrated that in ADM2(17-47)-treated rats Bcl
      2, mitochondrial cytochrome c, and active caspase-9 and caspase-3 were
      significantly increased compared with the controls. No significant treatment
      associated changes were observed in Bax, Bid, p53, and caspase-8 and caspase-10
      proteins in the treated placentas. In addition, infusion of ADM2(17-47) caused a
      significant decline in the transcripts of nitric oxide synthase 3 (NOS3) and
      NOS2. These findings show that ADM2(17-47) infusion in rats during midpregnancy
      cause fetoplacental growth restriction through the activation of mitochondrial
      apoptotic pathways. This study demonstrates for the first time (to our knowledge)
      a potential role for ADM2 in placental functions during pregnancy.

PMID- 16971559
TI  - Comparison of Vietnamese and European pig breeds using microsatellites.
AB  - This study characterized autochthonous pig breeds of Vietnam and compared them
      with breeds from other regions. A total of 343 animals were considered from 5
      indigenous pig breeds of Vietnam (Muong Khuong, Co, Meo, Tap Na, and Mong Cai), 2
      exotic breeds kept in Vietnam (Landrace and Yorkshire), 3 European commercial
      breeds (German Land-race, Pietrain, and Large White), the Chinese breed Meishan,
      and the European Wild Boar. Each individual was genotyped for 20 selected
      polymorphic microsatellite loci. The Vietnamese autochthonous breeds showed
      higher degrees of polymorphism, allelic diversity, and heterozygosity than the
      other pig breeds. Also, large genetic diversity was observed across the area of
      distribution, with village-specific subpopulations, which led to significant
      inbreeding coefficients. As expected, genetic distances showed large differences
      among European-based, Chinese, and Vietnamese indigenous breeds and reflected the
      geographical distribution of breeds. In comparison with the European breeds, the
      Vietnamese indigenous pig breeds harbored a considerable amount of genetic
      diversity and, therefore, will be of significance for livestock bioconservation.

PMID- 16971560
TI  - Parametric bootstrap for testing model fitting in the proportional hazards
      framework: an application to the survival analysis of Bruna dels Pirineus beef
      calves.
AB  - Given that correct assumptions on the baseline survival function are determinant
      for the validity of further inferences, specific tools to test the fit of a model
      to real data become essential in proportional hazards models. In this sense, we
      have proposed a parametric bootstrap to test the fit of survival models. Monte
      Carlo simulations are used to generate new data sets from the estimates obtained
      through the assumed models, and then bootstrap intervals can be established for
      the survival function along the time space studied. Significant fitting
      deficiencies are revealed when the real survival function is not included within
      the bootstrap interval. We tested this procedure in a survival data set of Bruna
      dels Pirineus beef calves, assuming 4 parametric models (exponential, Weibull,
      exponential time-dependent, Weibull time-dependent) and the Cox's semiparametric
      model. Fitting deficiencies were not observed for the Cox's model and the
      exponential time-dependent model, whereas the Weibull time-dependent model
      suffered from moderate overestimation at different ages. Thus, the exponential
      time-dependent model appears to be preferable because of its correct fit for
      survival data of beef calves and its smaller computational and time requirements.
      Exponential and Weibull models were completely rejected due to the continuous
      over- and underestimation of the survival probability reported. Results here
      highlighted the flexibility of parametric models with time-dependent effects,
      achieving a fit comparable to nonparametric models.

PMID- 16971561
TI  - Genetic analysis of calf market weight and carcass traits in Japanese Black
      cattle.
AB  - Heritabilities of and genetic correlations between additive direct and maternal
      genetic effects for calf market weight, and additive direct genetic effects for
      carcass traits, were estimated for Japanese Black cattle by REML procedures under
      2-trait animal models. Data were collected from calf and carcass markets in Hyogo
      and Tottori prefectures and analyzed separately by prefecture. Calf market weight
      was measured on 42,745 and 23,566 calves in Hyogo and Tottori, respectively. Only
      the fattening animals with calf market weight were extracted from the carcass
      database and used for estimation. The carcass traits analyzed were carcass
      weight, ribeye area, rib thickness, subcutaneous fat thickness, yield estimate,
      beef marbling score, and 4 meat characters (color, brightness, firmness, and
      texture). Direct and maternal heritabilities for calf market weight were
      estimated to be 0.22 and 0.07 in Hyogo, and 0.37 and 0.15 in Tottori,
      respectively. The estimates of heritabilities for carcass traits were moderate to
      high in both prefectures. The estimates of direct-maternal genetic correlations
      for calf market weight were positive (0.17) in Hyogo and negative (-0.63) in
      Tottori. The direct effect for calf market weight was positively correlated with
      the direct effect for carcass weight (0.87 and 0.56 in Hyogo and Tottori,
      respectively) but negatively correlated with the direct effect for beef marbling
      score (-0.10 in both prefectures). The estimates of genetic correlations between
      the maternal effect for calf market weight and the direct effects for carcass
      traits varied from -0.13 to 0.34 in Hyogo and from -0.14 to 0.15 in Tottori.
      Because direct and maternal genetic effects for early growth traits can be
      evaluated from calf market weight data in the production system of Japanese Black
      cattle, this information should be incorporated into selection and mating schemes
      of the breed.

PMID- 16971562
TI  - Quantitative genetic aspects of coat color in horses.
AB  - The aim of this study was to estimate genetic parameters for coat color in
      horses. Besides defining coat color classes (gray, chestnut, bay, and black), the
      phenotypes were also measured quantitatively according to standardized
      international procedures (Commission Internationale de l'Eclairage L*, a*, b*),
      where L* describes lightness, a* describes color saturation from red to green,
      and b* describes color saturation from yellow to blue. The total color saturation
      was derived from a* and b* and referred to as Chroma. A total of 294 horses from
      the breeds Lipizzan, Nonius, Arabian Pure Bred, Shagya Arabian, and Gidran were
      measured at neck, shoulder, and belly. Heritabilities (within and between breeds
      or color classes) and repeatabilities were estimated using REML from univariate
      animal models defined separately for gray and nongray horses. For gray horses,
      the estimated within-breed heritabilities for L* ranged from 0.45 to 0.49 and for
      a*, b*, and Chroma from 0.09 to 0.52, indicating moderate polygenic effect. For
      nongray horses, between-color class heritabilities were high (0.70 to 0.85) and
      within-color class heritabilities were negligible (except for L* measured on neck
      and belly, 0.21 and 0.34, respectively). Additionally, the importance of L* was
      described by the relation with the total melanin content of horse coat hair; for
      gray and nongray horses, a strong negative linear relationship was detected (P <
      0.01). The spectrometric measures and the results of this study demonstrate a
      possible approach to the estimation of the polygenic component involved in coat
      color inheritance.

PMID- 16971563
TI  - Changes in disease gene frequency over time with differential genotypic fitness
      and various control strategies.
AB  - A spreadsheet model was constructed to describe the change in allelic frequency
      over time for a lethal recessive mutation in an animal population. The model
      allowed relative fitness to differ between genotypes, between sexes, and over
      time. Whereas a lethal recessive allele is naturally eliminated very slowly from
      a population, a small selective disadvantage of the heterozygote results in a
      large increase in the rate of elimination. With selective advantage of the
      heterozygote through linkage with a production trait or pleiotropy, the allele is
      never naturally eliminated but tends toward a stable equilibrium frequency. The
      model was used to investigate various alternative control programs based on the
      detection of heterozygotes by genotyping and their exclusion from breeding. The
      programs (genotyping males only, genotyping males and 50% of females, and
      genotyping all breeding animals) were modeled for various initial heterozygote
      frequencies, and the results were described in terms of the number of
      generations, number of tests, and number of culls required to reduce the
      heterozygote frequency to a predefined level. The model can be used to compare
      the feasibility and cost of various control strategies and to illustrate clearly
      to breeders the expected outcomes, as well as the danger of prematurely
      terminating a control program when there is a selective advantage of the
      heterozygote.

PMID- 16971565
TI  - A genetic investigation of various growth models to describe growth of lambs of
      two contrasting breeds.
AB  - This study compared the use of various models to describe growth in lambs of 2
      contrasting breeds from birth to slaughter. Live BW records (n = 7559) from 240
      Texel and 231 Scottish Blackface (SBF) lambs weighed at 2-wk intervals were
      modeled. Biologically relevant variables were estimated for each lamb from
      modified versions of the logistic, Gompertz, Richards, and exponential models,
      and from linear regression. In both breeds, all nonlinear models fitted the data
      well, with an average coefficient of determination (R2) of > 0.98. The linear
      model had a lower average R2 than any of the nonlinear models (< 0.94). The
      variables used to describe the best 3 models (logistic, Gompertz, and Richards)
      included estimated final BW (A); maximum ADG (B); age at maximum ADG (C);
      position of point of inflection in relation to A (D, for Richards only). The
      Richards and Gompertz models provided the best fit (average R2 = 0.986 to 0.989)
      in both breeds. Richards estimated an extra variable, allowing increased
      flexibility in describing individual growth patterns, but the Akaike's
      information criteria value (which weighs log-likelihood by number of parameters
      estimated) was similar to that of the Gompertz model. Variables A, B, C, and D
      were moderately to highly heritable in Texel lambs (h2 = 0.33 to 0.87), and
      genetic correlations between variables within-model ranged from -0.80 to 0.89,
      suggesting some flexibility to change the shape of the growth curve when
      selecting for different variables. In SBF lambs, only variables from the logistic
      and Gompertz models had moderate heritabilities (0.17 to 0.56), but with high
      genetic correlations between variables within each model (< -0.88 or > 0.92).
      Selection on growth variables seems promising (in Texel more than SBF), but high
      genetic correlations between variables may restrict the possibilities to change
      the growth curve shape. A random regression model was also fitted to the data to
      allow predictions of growth rates at relevant time points. Heritabilities for
      growth rates differed markedly at various stages of growth and between the 2
      breeds (Texel: 0.14 to 0.74; SBF: 0.07 to 0.34), with negative correlations
      between growth rate at 60 d of age and growth rate at finishing. Following these
      results, future studies should investigate genetic relationships between relevant
      growth curve variables and other important production traits, such as carcass
      composition and meat quality.

PMID- 16971564
TI  - Effect of lactoferrin on the growth performance, intestinal morphology, and
      expression of PR-39 and protegrin-1 genes in weaned piglets.
AB  - A total of 90 weaned female pigs (Duroc x Landrace x Yorkshire) were used in a 15
      d growth experiment to investigate the effect of lactoferrin on growth
      performance, intestinal morphology, and expression of PR-39 and protegrin-1
      genes. The pigs were allocated on the basis of BW and litter to 3 dietary
      treatments in a randomized complete block design. There were 3 replicate pens per
      treatment, and the pigs were grouped with 10 pigs per pen. The dietary treatments
      were (1) basal diet; (2) basal diet + 20 mg of flavomycin/kg + 110 mg of
      aureomycin/kg; (3) basal diet + 1.0 g of lactoferrin/kg. Six pigs, randomly
      selected from each treatment (2 piglets/pen) were slaughtered for intestinal
      morphology and expression of PR-39 and protegrin-1 genes at the end of the
      experiment. Supplementation with lactoferrin improved growth performance; it
      increased ADG by 41.80% (P < 0.01) and efficiency of gain (G:F) by 17.20% (P <
      0.05). Intestinal villus height was increased by 15.30% (P < 0.05), and crypt
      depth was decreased by 9.60% (P < 0.05). Supplemental lactoferrin increased the
      relative abundance of mRNA for PR-39 and protegrin-1 by 143% (P < 0.01) and 217%
      (P < 0.01), respectively. The use of lactoferrin as an additive to improve
      nonspecific immunity and strengthen host defenses would be good a method of
      defending weaned pigs from infections and weanling stress.

PMID- 16971566
TI  - Porcine peroxisome proliferator-activated receptor gamma induces
      transdifferentiation of myocytes into adipocytes.
AB  - Peroxisome proliferator-activated receptor gamma2 (PPARgamma) is a nuclear
      transcription factor that regulates adipocyte differentiation and lipogenic genes
      during adipogenesis. The activity of rodent PPARgamma is regulated by
      phosphorylation of serine 112. The current experiment was designed to study the
      ability of porcine PPARgamma to stimulate transdifferentiation of myoblasts to
      adipocytes by overexpressing wild-type PPARgamma or mutated PPARgamma (serine 112
      was mutated to alanine) in mouse myoblast cells. The expression of adipogenic
      marker genes (adipocyte fatty acid binding protein, lipoprotein lipase, and
      glycerol-3 phosphate dehydrogenase) in cells stably expressing mutated porcine
      PPARgamma was greater than in cells with wild-type PPARgamma, indicating that the
      mutated PPARgamma has greater adipogenic capability than the wild-type PPARgamma.
      Under treatment with a ligand, both wild-type and mutant porcine PPARgamma
      expressing C2C12 myoblasts differentiated into adipocytes in 10 d. The expression
      of myogenic marker genes (myogenin, myogenic regulatory factor-4) was suppressed
      in cells transfected with the mutated PPARgamma or wild-type PPARgamma. Moreover,
      wild-type and mutant PPARgamma were able to inhibit myogenesis without addition
      of a ligand. Our results suggest that porcine wild-type PPARgamma and mutated
      PPARgamma can both convert myoblast cells into adipocytes, and also that the
      ability to transdifferentiate was greater in cells containing the mutated
      PPARgamma than in cells containing the wild-type PPARgamma. Therefore, the
      existence of serine 112 in PPARgamma may have a role in regulating adipocyte
      differentiation.

PMID- 16971567
TI  - Using ultrasound measurements to predict body composition of yearling bulls.
AB  - Carcass traits have been successfully used to determine body composition of
      steers. Body composition, in turn, has been used to predict energy content of ADG
      to compute feed requirements of individual animals fed in groups. This
      information is used in the Cornell value discovery system (CVDS) to predict DM
      required (DMR) for the observed animal performance. In this experiment, the
      prediction of individual DMR for the observed performance of group-fed yearling
      bulls was evaluated using energy content of gain, which was based on ultrasound
      measurements to estimate carcass traits and energy content of ADG. One hundred
      eighteen spring-born purebred and crossbred bulls (BW = 288 +/- 4.3 kg) were
      sorted visually into 3 marketing groups based on estimated days to reach USDA low
      Choice quality grade. The bulls were fed a common high-concentrate diet in 12
      slatted-floor pens (9 to 10 head/pen). Ultrasound measurements including back-fat
      (uBF), rump fat, LM area (uLMA), and intramuscular fat were taken at
      approximately 1 yr of age. Carcass measurements including HCW, backfat over the
      12th to 13th rib (BF), marbling score (MRB), and LM area (LMA) were collected for
      comparison with ultrasound data for predicting carcass composition. The 9th to
      11th-rib section was removed and dissected into soft tissue and bone for
      determination of chemical composition, which was used to predict carcass fat and
      empty body fat (EBF). The predicted EBF averaged 23.7 +/- 4.0%. Multiple
      regression analysis indicated that carcass traits explained 72% of the variation
      in predicted EBF (EBF = 16.0583 + 5.6352 x BF + 0.01781 x HCW + 1.0486 x MRB -
      0.1239 x LMA). Because carcass traits are not available on bulls intended for use
      as herd sires, another equation using predicted HCW (pHCW) and ultrasound
      measurements was developed (EBF = 39.9535 x uBF - 0.1384 x uLMA + 0.0867 x pHCW -
      0.0897 x uBF x pHCW - 1.3690). This equation accounted for 62% of the variation
      in EBF. The use of an equation to predict EBF developed with steer composition
      data overpredicted the EBF predicted in these experiments (28.7 vs. 23.7%,
      respectively). In a validation study with 37 individually fed bulls, the use of
      the ultrasound-based equation in the CVDS to predict energy content of gain
      accounted for 60% of the variation in the observed efficiency of gain, with 1.5%
      bias, and identified 3 of the 4 most efficient bulls.

PMID- 16971568
TI  - Abundantly expressed genes in pig adipose tissue: an expressed sequence tag
      approach.
AB  - Adipose tissue plays a critical role in metabolism, storage, and release of fatty
      acids in mammals. Construction of a full-length cDNA library is an effective way
      to understand the functional expression of genes in adipose tissue, and in
      addition, novel genes for further research can be found in the library. In this
      study, adipose tissue RNA was extracted from three 18-mo-old Lee-Sung pigs. The
      mRNA was isolated, reverse transcribed, and used to construct a cDNA library.
      After transformation, 2,880 clones were selected and sequenced. Cluster analysis
      was performed, and the assembled contig of each cluster was subjected to search
      against DNA sequences in the nucleotide databases (NCBINR/TIGRGI). These
      sequences were clustered into 1,527 unique sequences; 80% of the sequences were
      categorized as known genes, and 20% of the sequences were categorized as unknown
      genes. In this adipose tissue cDNA library, approximately 16% of the genes
      contained full-length sequences with start and stop codons. Gene ontology
      analysis was performed to indicate the possible functions of these genes. Genes
      associated with mitochondrial function were abundant and represented 10% of the
      total. Several fatty acid transport genes and stearoyl coenzyme A desaturase were
      among the most abundant genes expressed. Tissue distribution of several abundant
      genes was analyzed by northern analysis, and many of these genes were transcribed
      in porcine adipose tissue in high copy number. Our full-length sequence data and
      tissue distribution data can be used to decipher the functional roles exhibited
      by the adipocyte under various perturbations via endocrine, environmental,
      genetic, nutritional, pharmacological, or physiological manipulations.

PMID- 16971569
TI  - Nuclear receptor and nuclear receptor target gene messenger ribonucleic acid
      levels at different sites of the gastrointestinal tract and in liver of healthy
      dogs.
AB  - Nuclear receptors (NR) are ligand-activated transcription factors that regulate
      different metabolic pathways by influencing the expression of target genes. The
      current study examined mRNA abundance of NR and NR target genes at different
      sites of the gastrointestinal tract (GIT) and the liver of healthy dogs (Beagles;
      n = 11). Samples of GIT and liver were collected postmortem and homogenized,
      total RNA was extracted and reverse transcribed, and gene expression was
      quantified by real-time reverse-transcription PCR relative to the mean of 3
      housekeeping genes (beta-actin, glyceraldehyde-3-phosphate dehydrogenase, and ubi
      quitin). Differences were observed (P < or = 0.05) in the mRNA abundance among
      stomach (St), duodenum (Du), jejunum (Je), ileum (Il), and colon (Col) for NR
      [pregnane X receptor (Du, Je > Il, Col > St), peroxisome proliferator-associated
      receptor gamma (St, Du, Col > Je, Il), constitutive androstane receptor (Je, Du >
      Il, Col), and retinoid x receptor alpha (Du > Il)] and NR target genes
      [glutathione-S-transferase A3-3 (Du > Je > St, Il; St > Col), phenol-sulfating
      phenol sulfotransferase 1A1 (Du, Je > Il, St; Col > St), cytochrome P450 3A12
      (Du, Je > St, Il, Col), multiple drug resistance gene 1 (Du, Je, Il, Col > St),
      multiple drug resistance-associated protein 2 (Je, Du > Il > St, Col), multiple
      drug resistance-associated protein 3 (Col > St > Il; Du > Je, Il; St > Il), NR
      corepressor 2 (St > Il, Col), and cytochrome P450 reductase (St, Du, Je > Il,
      Col)], but not for peroxisome proliferator-associated receptor alpha. Differences
      (P > 0.05) in mRNA abundance in the liver relative to the GIT were also observed.
      In conclusion, the presence of numerous differences in expression of NR and NR
      target genes in different parts of the GIT and in liver of healthy dogs may be
      associated with location-specific functions and regulation of GIT regions.

PMID- 16971570
TI  - Factors influencing boar sperm cryosurvival.
AB  - Optimal sperm cryopreservation is a prerequisite for the sustainable commercial
      application of frozen-thawed boar semen for AI. Three experiments were performed
      to identify factors influencing variability of postthaw sperm survival among 464
      boar ejaculates. Sperm-rich ejaculate fractions were cryopre-served using a
      standard freezing-thawing procedure for 0.5-mL plastic straws and computer
      controlled freezing equipment. Postthaw sperm motility (assessed with a computer
      assisted semen analysis system) and viability (simultaneously probed by flow
      cytometry analysis after triple-fluorescent stain), evaluated 30 and 150 min
      postthaw, were used to estimate the success of cryopreservation. In the first
      experiment, 168 unselected ejaculates (1 ejaculate/boar), from boars of 6 breeds
      with a wide age range (8 to 48 mo), were cryopreserved over a 12-mo period to
      evaluate the predictive value of boar (breed and age), semen collection,
      transport variables (season of ejaculate collection, interval between
      collections, and ejaculate temperature exposure), initial semen traits, and sperm
      quality before freezing on sperm survival after freezing-thawing. In Exp. 2, 4
      ejaculates from each of 29 boars, preselected according to their initial semen
      traits and sperm quality before freezing, were collected and frozen over a 6-mo
      period to evaluate the influence of interboar and intraboar ejaculate variability
      in the survival of sperm after cryopreservation. In Exp. 3, 12 ejaculates
      preselected as for Exp. 2, from each of 15 boars with known good sperm
      cryosurvival, were collected and frozen over a 12-mo period to estimate the
      sustainability of sperm cryosurvival between ejaculates over time. Boar and semen
      collection and transport variables were not predictive of sperm cryosurvival
      among ejaculates. Initial semen traits and sperm quality variables observed
      before freezing explained 23.2 and 10.9%, respectively, of the variation in
      postthaw sperm motility and viability. However, more that 70% of total variance
      observed in postthaw sperm quality variables among ejaculates was explained by
      boar. This indicates that boar is the most important (P < 0.001) factor
      explaining the variability among ejaculates in sperm cryosurvival, with most (14
      of the 15 boars in Exp. 3) showing consistent (P > 0.05) sperm cryosurvival over
      time.

PMID- 16971571
TI  - Endocrine responses in mares undergoing abrupt changes in nutritional management.
AB  - Leptin, a protein hormone secreted by adipocytes, plays an important role in
      energy homeostasis and regulation of body composition. We previously observed
      that acute feed restriction resulted in a rapid decline in concentrations of
      leptin in obese pony mares. This acute response prompted us to characterize the
      temporal changes in concentrations of leptin, GH, and insulin in obese pony mares
      during the transition between fed and feed-restricted conditions. Nine obese pony
      mares of mixed breed, previously maintained on fescue pasture, were randomly
      allotted to 2 groups. Treatments consisted of a 48-h feed restriction, a 48-h
      refeeding, and a 24-h feed restriction (RFR; n = 4), or 48 h of alfalfa hay ad
      libitum, a 48-h feed restriction, and a 24-h refeeding (FRF; n = 5). Blood
      samples were taken every 15 min during restriction and feeding transitions (0600
      to 1400 on d 2 and 4), and every 30 min thereafter until 0830 of the following
      days (d 3 and 5). In the FRF treatment, plasma concentrations of leptin declined
      precipitously 6 h after the removal of feed (sample by treatment interaction; P <
      0.01), and remained low and unresponsive to refeeding. Similarly, in the RFR
      group, plasma concentrations of leptin were initially low, and did not respond to
      feeding during the second (refeeding) sampling period. After feed restriction in
      each of the 2 treatment sequences, plasma insulin decreased and GH mean
      concentration, pulse frequency, pulse amplitude, and area under the curve
      increased (P < 0.05). Refeeding reversed these effects on insulin and GH. These
      data provide evidence that peripheral concentrations of insulin and GH are
      dynamically responsive to feed removal (decrease in insulin; increase in GH) and
      replacement (increase in insulin; decrease in GH), whereas leptin decreases in
      response to feed restriction but is slow to recover from a transient nutritional
      insult.

PMID- 16971572
TI  - Resumption of postpartum luteal function of primiparous, suckled beef cows
      exposed continuously to bull urine.
AB  - The objective of this experiment was to determine if continuous exposure to bull
      urine alters resumption of ovarian cycling activity of primiparous, suckled beef
      cows. We tested the hypotheses that interval from urine exposure to resumption of
      luteal activity and proportions of cows that resume luteal activity by the end of
      the urine-exposure period do not differ between cows exposed to mature bull urine
      or steer urine. Thirty-eight Angus (A) x Hereford (H) cows, 4 mature A x H bulls
      and four 10-mo-old A x H steers, were used in this study. Cows were stratified by
      calving date, cow BW, calf BW, calf sex, dystocia score, and BCS; fitted with a
      controlled urine delivery device 2 wk before the start of treatments; and
      assigned randomly to be exposed continuously (24 h/d) to bull urine (n = 19) or
      steer urine (n = 19) beginning 40 d after calving. Urine was collected from bulls
      and steers every third day of the experiment. Blood samples were collected from
      cows starting on d 0 and every third day thereafter until the end of the exposure
      period (approximately 64 d). Likewise, controlled urine delivery devices were
      filled and refilled on the same schedule. Neither interval from urine exposure to
      resumption of luteal activity nor proportions of cows that resumed luteal
      activity during the urine-exposure period differed between cows exposed to bull
      urine or steer urine. We concluded that continuous exposure to mature bull urine
      does not affect resumption of luteal activity of primiparous, suckled beef cows.

PMID- 16971573
TI  - Large variation in steroid concentrations and insulin-like growth factor binding
      proteins exists among individual small antral follicles collected from within
      cows at random stages of the estrous cycle.
AB  - Variation in the biochemical status of individual small (< or = 5 mm diameter)
      antral follicles within the ovaries of a cow at any given time likely influences
      the capacity for undergoing recruitment, selection, and establishing dominance.
      The objectives of this study were to provide insight into the magnitude of
      variation in follicular fluid concentrations of steroids and activities of IGFBP
      that exists among individual small antral follicles within and between cows, and
      to determine the relationships between follicular fluid IGFBP and steroid
      concentrations in these follicles. A total of 108 small antral follicles were
      collected from 6 cows at random stages of the estrous cycle, with 10 to 26
      follicles/cow. Concentrations of steroids (ng/mL of follicular fluid) in the
      overall population of follicles ranged from 0.1 (lowest detectable limit) to 51
      for estradiol (E2), 4 to 1,149 for progesterone (P4), and 5 to 504 for
      androstenedione (A4). Concentrations of E2 and A4 were associated positively (r =
      0.2; P < 0.02), but E2 (r = -0.4) and A4 (r = -0.4) were associated negatively,
      with P4. The proportion of variation in steroid concentrations accounted for by
      differences among animals (P < 0.05) was small for E2 (12%), moderate for P4
      (43%), and greatest for A4 (74%). Least differences between minimum and maximum
      concentrations of steroids observed in follicles from within a cow were 21-, 5.5
      , and 3.5-fold for E2, P4, and A4, respectively, whereas the greatest differences
      between minimum and maximum concentrations were 505-, 108-, and 26-fold for E2,
      P4, and A4, respectively. Ranges of IGFBP concentrations (arbitrary densitometer
      units) detected in fluid from a sub-sample of 43 follicles were 1.18 to 4.50 for
      IGFBP-3, 0.54 to 4.68 for IGFBP-2, 0.07 to 2.56 for IGFBP-4, and 0.01 to 6.71 for
      IGFBP-5. Concentrations of E2 were correlated negatively with each IGFBP (r = 
      0.4 to -0.8; P < 0.05) except IGFBP-3. In contrast, concentrations of A4 were
      correlated positively with IGFBP-3 (r = 0.4; P < 0.05) but were not correlated
      with other IGFBP. Concentrations of P4 were correlated positively (r > 0.4; P <
      0.05) with IGFBP-4 and -5. The results indicate that steroid concentrations and
      IGFBP activities vary substantially among small antral follicles collected from
      within and among individual animals and that increasing production of E2, the
      hallmark of a developing follicle, was associated with reduced activity of all
      IGFBP except IGFBP-3, thereby implicating these IGFBP in the regulation of
      follicular recruitment.

PMID- 16971574
TI  - The response of gastrointestinal microbiota to avilamycin, butyrate, and plant
      extracts in early-weaned pigs.
AB  - An experiment was designed to evaluate the effects of 3 different additives on
      the gastrointestinal microbiota of early-weaned pigs. Early-weaned (18 to 22 d; n
      = 32) pigs (6.0 +/- 0.10 kg of BW) from 8 litters were randomly distributed into
      8 pens. Each pen was assigned 1 of 4 dietary treatments: a prestarter or control
      diet, the control diet with 0.04% avilamycin (AB), with 0.3% sodium butyrate, or
      with 0.03% plant extract mixture (XT; standardized mixture with 5% (wt/wt)
      carvacrol extracted from Origanum spp., 3% cinnamaldehyde extracted from
      Cinnamonum spp., and 2% capsicum oleoresin from Capsicum annum). At the end of
      the experimental period, 8 pigs per treatment were killed, and samples of their
      intestinal content were taken. The total bacterial load along the
      gastrointestinal tract (GIT; stomach, jejunum, cecum, and distal colon) and the
      lactobacilli and enterobacteria in the jejunum and cecum were measured by
      quantitative PCR. The total microbial counts along the GIT did not differ among
      the diets, but there was an increase in the lactobacilli:enterobacteria ratio in
      the cecum of the piglets on the XT diet (P = 0.003). Restriction fragment length
      polymorphism of the PCR-amplified V3, V4, and V5 regions of the 16S rDNA gene
      showed changes in the structure of the microbial community in the jejunum.
      Dendrograms grouped animals by diets; control with 0.3% sodium butyrate was the
      treatment that promoted the biggest changes in the microbial ecosystem, followed
      by AB and then XT. Biodiversity increased when using additives compared with the
      control diet (P = 0.002). Microbial metabolic activity along the hindgut was
      studied using the concentration of purine bases and carbohydrase activities.
      Different patterns for purine bases were observed between diets (diet x
      intestinal section, P = 0.01). The control diet reached a maximum purine base
      concentration at the end of the colon, whereas that of the AB diet was reached at
      the cecum. We could not detect any cellulase or xylanase activities in animals of
      this age. Appreciable amylase and amylopectinase activities were found, but they
      did not differ between diets. The results suggest that the effects of avilamycin,
      butyrate, or the plant extract would not be related to a reduction in the number
      of total bacteria inhabiting different sections of the GIT but rather to changes
      in the ecological structure and metabolic activity of the microbial community.

PMID- 16971575
TI  - Effects of spray-dried porcine plasma and plant extracts on intestinal morphology
      and on leukocyte cell subsets of weaned pigs.
AB  - We evaluated the effects of a 6% spray-dried porcine plasma (SDPP) and a plant
      extracts mixture (XT; 5% carvacrol, 3% cinnamaldehyde, and 2% capsicum oleoresin)
      on the productive performance, intestinal morphology, and leukocyte cell subsets
      of early-weaned pigs compared with a control group. Morphometry of the jejunum,
      ileum, and colon, and immune cell analysis of blood, ileocolic lymph node (LN),
      and ileal Peyer's patches were done in 24 weaned pigs (20 +/- 2 d) at 19 or 21 d
      postweaning. Although SDPP and XT treatments did not increase ADG or ADFI, SDPP
      improved the G:F ratio (P = 0.024) compared with the control group. Dietary SDPP
      reduced the percentages of blood monocytes (P = 0.006) and macrophages in ileal
      Peyer's patches and LN (P = 0.04), of B lymphocytes (P = 0.04) and gammadelta+ T
      cells in LN (P = 0.009), and of intraepithelial lymphocytes (P = 0.026) as well
      as the density of lamina propria cells in the colon (P < 0.01). Dietary XT
      reduced intraepithelial lymphocyte numbers in jejunum (P = 0.034) and the
      percentages of blood cytotoxic cells (P = 0.07) and B lymphocytes in LN (P =
      0.03); however, XT increased blood monocytes (P = 0.038) and the density of
      lamina propria lymphocytes in the colon (P = 0.003). These results indicate that
      dietary SDPP and plant extracts can affect intestinal morphology and immune cell
      subsets of gut tissues and blood in weaned pigs. Furthermore, the effects of SDPP
      suggest lower activation of the immune system of the piglets.

PMID- 16971576
TI  - Effects of butyrate, avilamycin, and a plant extract combination on the
      intestinal equilibrium of early-weaned pigs.
AB  - We evaluated the effects of 3 additives, sodium butyrate (AC), avilamycin (AB),
      and a combination of plant extracts (XT), on the productive performance and the
      intestinal environment of the early-weaned pig. The XT was a standardized mixture
      with 5% (wt/wt) carvacrol (from Origanum spp.), 3% cinnamaldehyde (from
      Cinnamonum spp.), and 2% capsicum oleoresin (from Capsicum annum). Pigs (n = 32)
      weaned at 18 to 22 d of age with an initial BW of 6.0 +/- 0.10 kg were allocated
      to 8 pens that, in turn, were allocated to 4 treatments. The treatments included
      a basal diet (CT) or the basal diet supplemented with 0.3% of AC, 0.04% of AB, or
      0.03% of XT. Productive performance was determined during the initial 14 d
      postweaning. On d 19 and 21 of the experiment, the pigs were killed to allow
      collection of digesta and intestinal tissue to evaluate variables indicative of
      aspects of the gastrointestinal environment. Treatments AB and AC improved G:F (P
      = 0.012 and 0.003, respectively) compared with the CT. Butyrate included in the
      diet was only detected in the stomach but not in cranial jejunum. When compared
      with CT, AC produced a lower ileal starch digestibility (P = 0.002) and a lower
      whole-tract OM and starch digestibility (P = 0.001 and 0.003, respectively),
      related to a lower VFA concentration in the cranial colon (P = 0.082) and a
      numerically reduced branched VFA percentage in the rectum. The AB treatment
      diminished propionate production in caudal colon (P = 0.002) and rectum (P =
      0.012) compared with CT. The AC group exhibited deeper crypt depth in the jejunum
      without variations in villus height compared with CT (P = 0.042). The AC and AB
      groups also increased goblet cell presence in the colon (P = 0.001 and 0.032,
      respectively). On the other hand, AB and XT diminished intraepithelial
      lymphocytes in the jejunum (P = 0.003 and 0.034, respectively). The XT increased
      lymphocyte presence in the colon (P = 0.003). These results show the important
      influence of AB and AC on productive performance and on pig gut dynamics. The
      intestinal modifications observed for AB and AC compared with CT suggest distinct
      modes of action for each additive.

PMID- 16971577
TI  - Fish meals, fish components, and fish protein hydrolysates as potential
      ingredients in pet foods.
AB  - An experiment to determine the chemical composition and protein quality of 13
      fish substrates (pollock by-products, n = 5; fish protein hydrolysates, n = 5;
      and fish meals, n = 3) was conducted. Two of these substrates, salmon protein
      hydrolysate (SPH) and salmon meal with crushed bones (SMB), were used to
      determine their palatability as components of dog diets. Pollock by-products
      differed in concentrations of CP, crude fat, and total AA by 71, 79, and 71%,
      respectively, and GE by 4.1 kcal/g. Fish protein hydrolysates and fish meals were
      less variable (approximately 18, 14, and 17%, and 1.4 kcal/g, respectively).
      Biogenic amine concentrations were much higher in fish protein hydrolysates as
      compared with pollock by-products and fish meals. Pollock liver and viscera had
      the highest total fatty acid concentrations; however, red salmon hydrolysate and
      SMB had the highest total PUFA concentrations (49.63 and 48.60 mg/g,
      respectively). Salmon protein hydrolysate had the highest protein solubility in
      0.2% KOH. Based on calculations using immobilized digestive enzyme assay values,
      lysine digestibility of fish meal substrates was comparable to in vivo
      cecectomized rooster assay values and averaged approximately 90.3%. Also, pollock
      milt, pollock viscera, red salmon hydrolysate, and sole hydrolysate had
      comparable values as assessed by immobilized digestive enzyme assay and rooster
      assays. A chick protein efficiency ratio (PER) assay compared SMB and SPH to a
      whole egg meal control and showed that SMB had high protein quality (PER = 3.5),
      whereas SPH had poor protein quality (PER value less than 1.5). However, using
      whole egg meal as the reference protein, both fish substrates were found to be
      good protein sources with an essential AA index of 1.0 and 0.9 for SMB and SPH,
      respectively. In the dog palatability experiments, a chicken-based control diet
      and 2 diets containing 10% of either SPH or SMB were tested. Dogs consumed more
      of the SPH diet compared with the control, and similar amounts of the SMB and
      control diets. The intake ratios for each were 0.73 and 0.52, respectively.
      Salmon protein hydrolysate was especially palatable to dogs. These data suggest
      that chemical composition and nutritional quality of fish substrates differ
      greatly and are affected by the specific part of the fish used to prepare fish
      meals and fish protein hydrolysates.

PMID- 16971578
TI  - Influence of the amount of dietary fiber on the available energy from hindgut
      fermentation in growing pigs: use of cannulated pigs and in vitro fermentation.
AB  - Available energy from hindgut fermentation to pigs fed various amounts of dietary
      fiber was investigated using an in vivo-in vitro methodology. Six growing pigs
      fitted with a simple T-shaped cannula at the terminal ileum, and following a
      Latin-square design, were fed 3 diets differing in the content of non-starch
      polysaccharides (NSP): a low fiber diet (LFD, 77 g/kg of DM), a standard fiber
      diet (SFD, 160 g/kg of DM), and a high fiber diet (HFD, 240 g/kg of DM). After
      adaptation to the diet for 10 d, samples from feces and ileum were collected and
      analyzed for DM, energy, NSP, and chromic oxide; feces were also analyzed for
      short chain fatty acids (SCFA). Freeze-dried ileal samples (10 g/L) were
      fermented in vitro in a fecal slurry consisting of an anaerobic mineral salt
      medium and feces (50 g/L) from cannulated pigs fed the same diets. Available
      energy was calculated from the amount of SCFA produced in vitro after 48 h of
      incubation. Nonstarch polysaccharide content in the fermented material was
      measured to assess the in vitro degradation of this fraction. Increasing dietary
      NSP from 77 to 240 g/kg of feed DM increased (P < 0.001) ileal flow from 199 to
      468 g/kg of feed, leading to a reduction in the energy digested at the terminal
      ileum, from 15 to 11 MJ/kg of feed DM and an increment in energy digested in the
      hindgut, from 1.6 to 3.5 MJ/kg of feed DM. Total in vitro production of SCFA/kg
      of feed DM was dependent on the amount of ileal substrate available for
      fermentation; that is, increased concentrations of NSP in the diet led to an
      increase in the SCFA that may be available to the animal (P < 0.001). The molar
      ratio of SCFA produced in vitro was affected by diet; the high fiber diet showed
      the greatest (P = 0.004) proportion of acetic acid, and the low fiber diet showed
      a tendency (P = 0.081) to an increased butyric acid proportion compared with the
      other 2 diets. Net disappearance of NSP during fermentation in vivo and in vitro
      were compared and showed a close relationship (P < 0.001, slope = 0.906, r =
      0.960). In our experimental conditions, available energy as SCFA to the animal
      from hindgut fermentation increased with the concentration of dietary NSP (P <
      0.001) and provided between 7.1 and 17.6% of the total available energy.

PMID- 16971579
TI  - Growth performance and carcass characteristics of pigs fed short-season corn
      hybrids.
AB  - An experiment was conducted to determine growth performance, carcass
      characteristics, and fat quality of growing-finishing pigs fed diets based on
      short-season corn hybrids. Twenty-four individually housed, Cotswold, growing
      pigs with an initial BW of 41.4 (SD = 1.4) kg were blocked by BW and sex and
      randomly allotted from within block to 1 of 3 diets to give 8 replicate pigs per
      diet. Experimental diets consisted of a control based on barley and 2 diets based
      on corn as the main energy sources. A 3-phase feeding program for 20 to 50 kg
      (phase I), 50 to 80 kg (phase II), and 80 to 110 kg (phase III) of BW was used.
      Diets for each phase contained approximately 3.5 Mcal/kg of DE, with total lysine
      of 0.95, 0.75, and 0.64% in phase I, II, and III diets, respectively. Average
      daily gain, ADFI, and G:F were monitored weekly during each phase. Pigs were
      slaughtered after reaching a minimum BW of 100 kg to determine carcass
      characteristics. There were no effects of diet on ADG, ADFI, and G:F (0.45 +/-
      0.02, 0.34 +/- 0.02, and 0.31 +/- 0.02 for phase I, II, and III, respectively).
      Carcass length, dressing percent, LM area, loin depth, backfat thickness, belly
      firmness, and L*, b*, and a* fat color were not different across dietary
      treatments. Pigs fed one corn variety had no differences in fatty acid profile
      with barley-fed pigs, whereas those fed the other variety of corn had a greater
      (P < 0.05) concentration of PUFA in their backfat. The results indicate that
      growth performance, carcass characteristics, and fat quality of pigs fed diets
      based on short-season corn hybrids and those fed the barley-based diet were not
      different.

PMID- 16971580
TI  - A revised model for studying phosphorus and calcium kinetics in growing sheep.
AB  - The objective of the study was to revise a model of P kinetics proposed by Vitti
      et al. (2000) and extend its use to study Ca flows in growing sheep. Twelve Santa
      Ines male sheep, 8 mo of age, with average BW of 31.6 kg were injected with 32P
      and 45Ca to trace the movement of P and Ca in the body. The original model had 4
      pools representing the gut, plasma, soft tissues, and bone. In the revised model,
      instantaneous values rather than averages for pool derivatives were incorporated,
      and the model was extended to represent absorption and excretion of phytate P
      explicitly. The amendments improved the model, resulting in higher flows between
      plasma and bone than between plasma and tissue and, therefore, a more accurate
      representation of P metabolism. Phosphorus and Ca metabolism were then assessed
      conjointly using the revised model. The results showed that P and Ca metabolism
      are closely related as evidenced by the ratio of these minerals in the
      bidirectional flows between plasma and bone and between plasma and tissue.
      Phytate P digestibility was 47%, and P retention was negative (-1.4 g/d),
      suggesting that a feed characteristic impaired P utilization and led to P
      deficiency. The revised model provides an improved prediction of P and Ca
      metabolism that can be used to assess mineral requirements and to estimate losses
      to the environment.

PMID- 16971581
TI  - Effects of ractopamine and protein source on growth performance and carcass
      characteristics of feedlot heifers.
AB  - An experiment was conducted to determine the relationship between feeding
      ractopamine and different amounts of MP on growth and carcass characteristics of
      feedlot heifers. Seventy-two crossbred heifers (475 kg of initial BW) were fed
      individually a diet based on steam-flaked corn for ad libitum intake for 29 d.
      Heifers were implanted with 140 mg of trenbolone acetate and 14 mg of estradiol
      17beta 60 d before the experiment. Treatments were arranged as a 2 x 3 factorial
      and included 0 or 200 mg of ractopamine-HCl (23 ppm)/ d, and urea, solvent
      soybean meal, or expeller soybean meal (ESBM) as the predominant protein
      supplement. The amounts of MP supplied by the urea, solvent soybean meal, and
      ESBM diets were 688, 761, and 808 g/ d, respectively, calculated according to
      level 1 of the NRC model. Body weights were obtained 1 d before ractopamine
      feeding and at slaughter. Blood samples were obtained 1 d before starting the
      experiment and 13 d later. Ractopamine improved ADG, efficiency of gain, carcass
      adjusted ADG, and carcass-adjusted efficiency of gain (P < 0.01). For ADG,
      heifers demonstrated a ractopamine x protein source interaction (P < 0.05);
      heifers not fed ractopamine had greater ADG when fed ESBM than when fed urea,
      whereas for heifers fed ractopamine there were no differences (P > or = 0.10)
      among protein supplements. This interaction was not observed for carcass-adjusted
      ADG (P = 0.60). Final live weights (P = 0.02) and carcass weights (P = 0.01) were
      greater with ractopamine feeding. Carcass marbling scores and yield grades were
      not affected by ractopamine or protein source (P > or = 0.39). Plasma total alpha
      amino N and glucose concentrations decreased more from pretreatment
      concentrations when heifers were fed ractopamine (P < 0.05). Feeding ractopamine
      to heifers for 28 d before slaughter improved ADG and efficiency of gain without
      any large effects on carcass characteristics. The MP supply does not need to be
      increased from that provided by finishing diets based on steam-flaked corn with
      urea as the primary N supplement to allow the maximal response to ractopamine by
      finishing heifers.

PMID- 16971582
TI  - Effects of alfalfa extract, anise, capsicum, and a mixture of cinnamaldehyde and
      eugenol on ruminal fermentation and protein degradation in beef heifers fed a
      high-concentrate diet.
AB  - Four Holstein heifers (360 +/- 22 and 450 +/- 28 kg of BW in Exp. 1 and 2,
      respectively) fitted with ruminal trocars were used in 4 x 4 Latin square designs
      to evaluate the effects on ruminal microbial fermentation of the following: Exp.
      1, no additive, alfalfa extract (30 g/d, AEX), a mixture of cinnamaldehyde (0.18
      g/d) and eugenol (0.09 g/d; CIE1), and AEX and CIE1 in combination; and Exp. 2,
      no additive, anise oil (2 g/d), capsicum oil (1 g/d), and a mixture of
      cinnamaldehyde (0.6 g/d) and eugenol (0.3 g/d). Heifers were fed a 90:10
      concentrate:barley straw diet (16% CP; 25% NDF) for ad libitum intake. Each
      period consisted of 15 d for adaptation and 6 d for sampling. On d 16 to 18, DM
      and water intakes were measured. On d 19 to 21 ruminal contents were sampled at
      0, 3, 6, 9, and 12 h after feeding to determine ruminal pH and the concentrations
      of VFA, L-lactate, large peptides, small peptides plus AA (SPep+AA), and ammonia
      N. On d 20 and 21, samples of ruminal fluid were collected at 0 and 3 h after
      feeding to determine protozoal counts. In Exp. 1, CIE1 and AEX decreased (P <
      0.05) total DMI, concentrate DMI, and water intake. The increase (P < 0.05) in
      SPep+AA and the decrease (P < 0.05) in ammonia N when supplementing CIE1 suggest
      that deamination was inhibited. Treatment AEX increased (P < 0.05) the acetate to
      propionate ratio, which is less efficient for beef production. Treatment CIE1
      increased (P < 0.05) counts of holotrichs. Effects of AEX and CIE1 were not
      additive for many of the measured metabolites. In Exp. 2, treatments had no
      effect on ruminal pH, total VFA concentration, and butyrate proportion. The
      capsicum oil treatment increased (P < 0.05) DMI, water intake, and SPep+AA N
      concentration and decreased (P < 0.05) acetate proportion, branched-chain VFA
      concentration, and large peptide N concentration. The cinnamaldehyde (0.6 g/d)
      and eugenol (0.3 g/d) treatment decreased (P < 0.05) water intake, acetate
      proportion, branched-chain VFA, L-lactate, and ammonia N concentrations and
      increased (P < 0.05) propionate proportion and SPep+AA N concentration. The anise
      oil treatment decreased (P < 0.05) acetate to propionate ratio, branched-chain
      VFA and ammonia N concentrations, and protozoal counts. The results indicate that
      at the doses used a mixture of cinnamaldehyde and eugenol, anise oil, and
      capsicum oil may be useful as modifiers of rumen fermentation in beef production
      systems.

PMID- 16971583
TI  - Relationship between the expression of hepatic but not testicular 3beta
      hydroxysteroid dehydrogenase with androstenone deposition in pig adipose tissue.
AB  - This study investigated the relationship between expression of hepatic and
      testicular 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and accumulation of
      androstenone in adipose tissue because of its relation to boar taint. The
      experiments were performed on 13 Large White (50%) x Landrace (50%) and Meishan
      (25%) x Large White (25%) x Landrace (50%), pigs, which differed in the level of
      backfat androstenone. Our previous work showed that the major product of the
      hepatic androstenone metabolism is 3beta-androstenol. In this study, the
      formation of 3beta-androstenol was inhibited by the specific 3beta-HSD inhibitor
      trilostane. These results are the first direct confirmation that 3beta-HSD is the
      enzyme responsible for androstenone metabolism in the pig. The expression of the
      hepatic but not testicular 3beta-HSD protein showed a negative relationship with
      the level of backfat androstenone (r2 = 0.64; P < 0.001) and was accompanied by a
      reduced rate of the hepatic androstenone clearance. Low expression of 3beta-HSD
      protein in the liver of high androstenone pigs was also accompanied by a reduced
      level of 3beta-HSD mRNA (P < 0.001), which suggests a defective regulation of the
      hepatic 3beta-HSD expression at the level of transcription. In contrast,
      expression of the testicular 3beta-HSD protein did not differ between animals
      with high and low androstenone levels (P > 0.05) and was lower compared with the
      hepatic 3beta-HSD expression. Cloning and sequencing of the 3beta-HSD coding
      regions established that the hepatic and testicular 3beta-HSD cDNA have identical
      sequences, which were 98% similar to the human 3beta-HSD isoform I. It is
      suggested that expression of a single 3beta-HSD gene is regulated by different
      mechanisms in pig liver and testis. The liver-specific regulation of 3beta-HSD
      expression contributes to the low rate of hepatic androstenone metabolism and
      therefore can be considered as one of the factors regulating deposition of
      androstenone in pig adipose tissue and subsequent development of boar taint.

PMID- 16971584
TI  - Mitochondrial phospholipids of rat skeletal muscle are less polyunsaturated than
      whole tissue phospholipids: implications for protection against oxidative stress.
AB  - The fatty acid composition of phospholipids is an important determinant of
      membrane function. Although the mitochondria play a pivotal role in skeletal
      muscle function, the fatty acid composition of their individual phospholipids has
      not been examined. The purpose of this study was to determine the fatty acid
      profile of each phospholipid in rat skeletal muscle mitochondria and compare it
      with that of the whole muscle. Lipids were extracted from the gastrocnemius
      muscles of 10 Wistar rats, and phospholipids were separated by thin-layer
      chromatography. The fatty acid composition of each phospholipid was then
      determined by gas chromatography. The same procedure was applied to a
      mitochondrial preparation from these muscles. We found that the fatty acid
      composition of the individual mitochondrial phospholipids (phosphatidyl choline,
      phosphatidyl ethanolamine, cardiolipin, phosphatidyl inositol, phosphatidyl
      serine, sphingomyelin, and lysophosphatidyl choline) and of the total
      mitochondrial phospholipids differed markedly (P < 0.05) from the fatty acid
      composition of the corresponding whole muscle phospholipids. Notably, the
      mitochondrial phospholipids had higher percentages of MUFA [13.9 (2.1) vs. 10.3
      (0.9)] and lower percentages of PUFA [34.8 (4.3) vs. 39.5 (5.2)] and n6 fatty
      acids [25.0 (2.5) vs. 27.6 (2.5)]. Overall, the mitochondrial phospholipids had a
      lower unsaturation index than whole muscle phospholipids [135 (20) vs. 161 (26)].
      Because PUFA are susceptible to peroxidation, unlike saturated fatty acids and
      MUFA, we propose that the low polyunsaturation of mitochondrial phospholipids is
      the result of selective pressure toward membranes that are more resistant to
      oxidative damage by reactive oxygen species produced in their vicinity. The
      negative effect of the low polyunsaturation on membrane fluidity may be
      counterbalanced by the higher percentage of MUFA and the known low cholesterol
      content of mitochondrial membranes.

PMID- 16971585
TI  - Flavor relationships among muscles from the beef chuck and round.
AB  - This research compared off-flavor notes and the relationship of pH and heme-iron
      content to off-flavor for different beef muscles. After grading, knuckles and
      shoulder clods were removed from 16 USDA Choice and 14 USDA Select beef
      carcasses, vacuum-packaged, and aged for 7 d. The rectus femoris (REC), vastus
      medalis (VAM), vastus lateralis (VAL), teres major (TER), infraspinatus (INF),
      and triceps brachii-long head (TRI) were separated, cut into steaks, and frozen (
      16 degrees C). Sensory analysis was conducted using a trained taste panel, with
      steaks grilled to an internal temperature of 65 degrees C. Heme-iron
      concentration and pH were determined. The INF had lower (P < 0.05) off-flavor
      intensity ratings and less frequent sour flavor than the other muscles, and the
      VAL had the most intense (P < 0.05) off-flavor ratings and among the greatest
      frequency of sour, charred, and oxidized flavors. The frequencies of liver-like,
      bloody, and rancid flavors were not affected by muscle type. Heme-iron
      concentration did not differ among muscles. Three USDA Select carcasses had
      intense off-flavor in the muscles. Liver-like flavor was highly negatively
      correlated with off-flavor intensity for each of the muscles tested. Muscles
      rated a 5 or below (on an 8-point rating scale, where 1 = extremely intense off
      flavor and 8 = no off-flavor) in off-flavor intensity and identified as liver
      like by 30% or more of the panelists were grouped together and compared to normal
      muscles. Those in the liver-flavored group were less frequently identified as
      charred, probably because the liver-like flavor was so intense. There were no
      differences between the 2 groups for sour, metallic, bloody, oxidized, or fatty
      off-flavor notes. Regression equations containing the linear and quadratic
      functions of heme-iron concentration, muscle pH, and their interaction were
      established for the frequency of off-flavor notes within each muscle. The REC,
      TER, VAL, and VAM showed a relationship between pH, heme iron, and off-flavor
      intensity (P < 0.05). Liver-like flavor was explained partially by pH and heme
      iron in the REC, VAM, and VAL (R2 = 0.45 to 0.55; P < 0.05). Few other
      significant relationships were found. Heme iron and pH were unrelated to
      metallic, oxidized, or rancid flavors for any of the muscles tested. These data
      suggest that liver-like off-flavors are specific to individual animals, and that
      pH and heme iron are not strongly related to off-flavor notes.

PMID- 16971586
TI  - Micro-calpain is essential for postmortem proteolysis of muscle proteins.
AB  - The objective of this investigation was to test the hypothesis that -calpain is
      largely responsible for postmortem proteolysis of muscle proteins. To accomplish
      this objective, we compared proteolysis of known muscle proteins in muscles of
      wild type and micro-calpain knockout mice during postmortem storage. Knockout
      mice (n = 6) were killed along with control mice (n = 6). Hind limbs were removed
      and stored at 4 degrees C. Muscles were dissected at 0, 1, and 3d postmortem and
      subsequently analyzed for degradation of nebulin, dystrophin, metavinculin,
      vinculin, desmin, and troponin T. In a separate experiment, hind limb muscles
      from knockout (n = 4) and control mice (n = 4) were analyzed at 0, 1, and 3 d
      postmortem using casein zymography to confirm that mu-calpain activity was
      knocked out in muscle and to determine whether or not m-calpain is activated in
      murine postmortem muscle. Cumulatively, the results of the first experiment
      indicated that postmortem proteolysis was largely inhibited in micro-calpain
      knockout mice. The results of the second experiment established the absence of
      micro-calpain in the muscle tissue of knockout mice and confirmed the results of
      an earlier study that m-calpain is active in postmortem murine muscle. The
      results of the current study show that even in a species in which m-calpain is
      activated to some extent postmortem, micro-calpain is largely responsible for
      postmortem proteolysis. This observation excludes a major role for any of the
      other members of the calpain family or any other proteolytic system in postmortem
      proteolysis of muscle proteins. Therefore, understanding the regulation of micro
      calpain in postmortem muscle should be the focus of further research on
      postmortem proteolysis and tenderization of meat.

PMID- 16971587
TI  - Changes in caspase activity during the postmortem conditioning period and its
      relationship to shear force in porcine longissimus muscle.
AB  - The objective of this study was to investigate the protease family caspases in
      skeletal muscle and their potential contribution to postmortem proteolysis and
      meat tenderization. Ten Large White gilts were slaughtered, and samples of LM
      were taken at 0, 2, 4, 8, 16, 32, and 192 h after slaughter and immediately snap
      frozen in liquid nitrogen. Samples were subsequently analyzed for caspase 3/7 and
      caspase 9 activity, protein levels of known caspase substrates, alpha II spectrin
      and poly (ADP-ribose) polymerase (PARP), as well as, at 192 h, shear force.
      Specific degradation products of alpha II spectrin and PARP, which are known
      indicators of caspase activity, and apoptosis were detected on immunoblots of
      muscle samples taken over the postmortem period. The relationships between the
      changes observed in caspase activities and protein levels of PARP and spectrin
      across the entire postmortem conditioning period were investigated (n = 70).
      Protein levels of alpha II spectrin cleavage products across the conditioning
      period were found to correlate positively to caspase 3/7 activity (r = 0.38, P =
      0.003) and caspase 9 activity (r = 0.32, P = 0.012), indicating that caspase
      mediated cleavage was occurring in situ. There was a negative relationship
      between shear force and the 0 to 32 h ratio of caspase 3/7 (r = -0.62, P = 0.053)
      and caspase 9 activities (r = -0.68, P = 0.044). In addition, there was also a
      negative relationship between shear force and the level of the caspase-generated
      alpha II spectrin 120 kDa degradation product (r = -0.75, P = 0.012). The
      findings of this study indicate that changes in caspase activity and caspase
      mediated cleavage take place in muscle during the conditioning period, and this
      could be associated with the development of tender meat.

PMID- 16971588
TI  - Socializing piglets before weaning: effects on behavior of lactating sows, pre-
      and postweaning behavior, and performance of piglets.
AB  - This study evaluated how socializing piglets before weaning affects behavior of
      lactating sows and the pre- and postweaning behavior and performance of piglets.
      Two farrowing rooms, each with 6 pens, and 1 nursery with 4 pens were used. In
      total, data were obtained from 24 sows and their litters. In each farrowing room,
      the solid barriers between 3 farrowing pens were removed on d 12 after farrowing,
      and the sows remained confined in their crates (experimental group). In the other
      3 farrowing pens of each farrowing room, sows and their litters were kept under
      conventional conditions until weaning (control group). All piglets were weaned 28
      d after birth. After weaning, piglets from each group remained together in 1 pen
      of the nursery. The behavior of sows (lying, standing, sitting, nursing) and
      piglets (lying, active, suckling) in the farrowing rooms was observed for 24 h
      before and for 48 h after removal of the barriers between the pens. In addition,
      behavior (active, lying, feeding, agonistic behavior) of piglets was observed in
      the nursery during the initial 48-h period after weaning. Each piglet was weighed
      on d 5, 12, and 28 after birth and thereafter weekly until the fifth week of
      rearing. In the farrowing room, mixing of litters did not influence behavior of
      piglets and sows. Preweaning weight gain of the piglets did not differ (P = 0.60)
      between the treatments. In the initial 48 h after weaning, less agonistic
      behavior (P < 0.001) was observed in piglets belonging to the experimental group.
      During 5 wk of rearing, piglets in the experimental group gained more weight
      compared with the control group (P = 0.05). The advantage shown by the
      experimental group became especially conspicuous in the first week after weaning
      (P = 0.05). By socializing unfamiliar piglets before weaning, stress due to
      mixing could at least be distanced in time from the other burdens of weaning,
      thereby improving performance.

PMID- 16971589
TI  - Effect of floor space during transport of market-weight pigs on the incidence of
      transport losses at the packing plant and the relationships between transport
      conditions and losses.
AB  - Data on 74 trailer loads of finishing pigs (mean BW = 129.0, SEM = 0.63 kg) from
      wean-to-finish buildings on 2 farms within 1 production system were collected to
      investigate the effect of amount of floor space on the trailer (0.39 or 0.48
      m2/pig) during transport on the incidence of losses (dead and nonambulatory pigs)
      at the packing plant and to study the relationships between transport conditions
      and losses. Pigs were loaded using standard commercial procedures for pig
      handling and transportation. Two designs of flat-deck trailers with 2 decks were
      used. Floor space treatments were compared in 2 similarly sized compartments on
      each deck of each trailer type. Differences in floor space were created by
      varying the number of pigs in each compartment. The incidence of nonambulatory
      pigs at the farm during loading and at the plant after unloading, average load
      weight, load number within each day, event times, and temperature and relative
      humidity in the trailer from loading to unloading were recorded. Of the 12,511
      pigs transported, 0.26% were non-ambulatory at the farm, 0.23% were dead on
      arrival, and 0.85% were nonambulatory at the plant. Increasing transport floor
      space from 0.39 to 0.48 m2/pig reduced the percentage of total nonambulatory pigs
      (0.62 vs. 0.27 +/- 0.13%, respectively; P < 0.05), nonambulatory, noninjured pigs
      (0.52 vs. 0.15 +/- 0.11%, respectively; P < 0.01), and total losses (dead and
      nonambulatory pigs) at the plant (0.88 vs. 0.36 +/- 0.16%, respectively; P <
      0.05) and tended to reduce dead pigs (0.27 vs. 0.08 +/- 0.08%, respectively; P =
      0.06). However, transport floor space did not affect the percentage of
      nonambulatory, injured pigs at the plant. Nonambulatory pigs at the farm were
      positively correlated with relative humidity during loading and load number
      within the day (r = 0.46 and 0.25, respectively; P < 0.05). The percentage of
      total losses at the plant was positively correlated to waiting time at the plant,
      unloading time, and total time from loading to unloading (r = 0.24, 0.51, and
      0.36, respectively; P < 0.05). Average temperature during loading, waiting at the
      farm, transport, waiting at the plant, unloading, and average pig weight on the
      trailer were not correlated to losses. These results suggest that floor space per
      pig on the trailer and transport conditions can affect transport losses.

PMID- 16971590
TI  - Retention of different sizes of electronic identification boluses in the
      forestomachs of sheep.
AB  - Twelve types of electronic identification ruminal boluses of different dimensions
      were used to obtain a model for predicting their retention in the forestomachs of
      sheep. Boluses (n = 1,662) were made of ceramic materials, and their dimensions
      varied in o.d. (9 to 21 mm), length (37 to 68 mm), volume (2.5 to 21.0 mL), and
      specific gravity (0.85 to 3.91). Each bolus contained a half-duplex,
      standardized, glass-encapsulated transponder (32 x 3.8 mm). Boluses were
      administered to sheep (n = 1,497) of different ages by using the appropriate
      balling guns, and their retention under semiintensive conditions was recorded for
      at least 2 yr. When a bolus was lost, the sheep was rebolused with a heavier
      bolus. All sheep wore 2 plastic ear tags: one for the official control of health
      programs and the other for farm use. To determine the anatomical limit for a
      bolus passing through the gastrointestinal tract, the size of the reticulo-omasal
      orifice was measured in 46 adult sheep (male, n = 14; female, n = 32) that died
      by causes not related to bolus administration during the experiment. No signs of
      disease or growth alteration were detected in the bolused sheep. Total ear tag
      losses during the experiment period were 7.5% on average. Bolus retention (5 to
      100%) varied according to bolus features and age of the sheep, but it showed a
      plateau after 18 mo. Inadequately dimensioned boluses were regurgitated or passed
      through the gastrointestinal tract and were excreted with the feces. The diameter
      of the reticulo-omasal orifice in adult sheep differed between male and female
      (23.1 and 21.8 mm, respectively; P < 0.01) and was greater than the o.d. of the
      retained boluses. Retention rate was predicted from bolus weight and volume by a
      logistic regression (R2 = 0.997; P < 0.001). When retention data from the
      literature (59.0 to 100%) were included in the model, the adjustment was slightly
      lower (R2 = 0.967). As a result, the minimum bolus weight estimated to reach a
      99.5% retention rate in sheep varied between 16 and 45 g when volume varied
      between 3 and 22 mL, for boluses with a specific gravity between 2.0 and 5.2. In
      conclusion, bolus retention rate in sheep varied dramatically according to their
      features. For safe and efficient retention of electronic identification boluses
      in sheep, boluses of small volume and diameter (e.g., < 15 mm) with specific
      gravity and weight greater than 3.0 and 20 g, respectively, are recommended.

PMID- 16971591
TI  - In vitro bacterial growth and in vivo ruminal microbiota populations associated
      with bloat in steers grazing wheat forage.
AB  - The role of ruminal bacteria in the frothy bloat complex common to cattle grazing
      winter wheat has not been previously determined. Two experiments, one in vitro
      and another in vivo, were designed to elucidate the effects of fresh wheat forage
      on bacterial growth, biofilm complexes, rumen fermentation end products, rumen
      bacterial diversity, and bloat potential. In Exp. 1, 6 strains of ruminal
      bacteria (Streptococcus bovis strain 26, Prevotella ruminicola strain 23,
      Eubacterium ruminantium B1C23, Ruminococcus albus SY3, Fibrobacter succinogenes
      ssp. S85, and Ruminococcus flavefaciens C94) were used in vitro to determine the
      effect of soluble plant protein from winter wheat forage on specific bacterial
      growth rate, biofilm complexes, VFA, and ruminal H2 and CH4 in mono or coculture
      with Methanobrevibacter smithii. The specific growth rate in plant protein medium
      containing soluble plant protein (3.27% nitrogen) was measured during a 24-h
      incubation at 39 degrees C in Hungate tubes under a CO2 gas phase. A monoculture
      of M. smithii was grown similarly, except under H2:CO2 (1:1), in a basal
      methanogen growth medium supplemented likewise with soluble plant protein. In
      Exp. 2, 6 ruminally cannulated steers grazing wheat forage were used to evaluate
      the influence of bloat on the production of biofilm complexes, ruminal microbial
      biodiversity patterns, and ruminal fluid protein fractions. In Exp. 1, cultures
      of R. albus (P < 0.01) and R. flavefaciens (P < 0.05) produced the most H2 among
      strains and resulted in greater (P < 0.01) CH4 production when cocultured with M.
      smithii than other coculture combinations. Cultures of S. bovis and E.
      ruminantium + M. smithii produced the most biofilm mass among strains. In Exp. 2,
      when diets changed from bermudagrass hay to wheat forage, biofilm production
      increased (P < 0.01). Biofilm production, concentrations of whole ruminal content
      (P < 0.01), and cheesecloth filtrate protein fractions (P < 0.05) in the ruminal
      fluid were greater on d 50 for bloated than for nonbloated steers when grazing
      wheat forage. The molecular analysis of the 16S rDNA showed that 2 different
      ruminal microbiota populations developed between bloated and nonbloated animals
      grazing wheat forage. Bloat in cattle grazing wheat pastures may be caused by
      increased production of biofilm, resulting from a diet-influenced switch in the
      rumen bacterial population.

PMID- 16971592
TI  - Decreasing the diagnostic cerebral angiogram requirements for neuroradiology
      fellows would be a mistake.

PMID- 16971593
TI  - Quantification of carotid stenosis on CT angiography--does gender matter?

PMID- 16971594
TI  - Post-transplant neurotoxicity: what role do calcineurin inhibitors actually play?

PMID- 16971595
TI  - Agenesis of bilateral internal carotid arteries in the PHACE syndrome.

PMID- 16971596
TI  - Magnetic resonance imaging of the fetal brain and spine: an increasingly
      important tool in prenatal diagnosis, part 1.
AB  - Fetal MR imaging is an increasingly available technique used to evaluate the
      fetal brain and spine. This is made possible by recent advances in technology,
      such as rapid pulse sequences, parallel imaging and advances in coil design. This
      provides a unique opportunity to evaluate processes that cannot be approached by
      any other current imaging technique and affords a unique opportunity for studying
      in vivo brain development and early diagnosis of congenital abnormalities
      inadequately visualized or undetectable by prenatal sonography. This 2-part
      review summarizes some of the latest developments in MR imaging of the fetal
      brain and spine and its application to prenatal diagnosis. This first part
      discusses the utility, safety, and technical aspects of fetal MR imaging, the
      appearance of normal fetal brain development, and the role of fetal MR imaging in
      the evaluation of fetal ventriculomegaly. The second part focuses on additional
      clinical applications of fetal MR imaging, including suspected abnormalities of
      the corpus callosum, malformations of cortical development, and spine
      abnormalities.

PMID- 16971597
TI  - Using the baseline CT scan to select acute stroke patients for IV-IA therapy.
AB  - BACKGROUND: Intra-arterial therapies for acute ischemic stroke are increasingly
      available. Intravenous therapy (IV) followed immediately by intra-arterial
      therapy (IA) has been shown to be safe, but such therapy is resource intensive.
      Selecting the best patients for this therapy may be accomplished with the use of
      baseline neuroimaging. METHODS: We used data from the IMS-1 and National
      Institute for Neurological Disorders and Stroke tissue plasminogen activator
      (tPA) stroke studies to compare outcomes among IV-IA tPA, IV-tPA, and placebo
      treatment stratified by the baseline CT scan appearance. The CT scans were scored
      using the Alberta Stroke Program Early CT (ASPECT) score and dichotomized into
      ASPECT score > 7 (favorable scan) and ASPECT score < or = 7 (unfavorable scan).
      Logistic regression was used to assess for an ASPECT score by treatment
      interaction. RESULTS: A total of 460 patients was included. Age and sex were
      similar among the 3 groups. The IV-IA tPA cohort had a higher median National
      Institutes of Health stroke scale (NIHSS) score (18 versus 17) compared with the
      IV tPA cohort. The proportion of patients with favorable CT scans (ASPECT score >
      7) was lowest in the IV-IA tPA group. A multiplicative interaction effect was
      shown indicating that patients with an ASPECT score > 7 in the IV-IA cohort were
      more likely to have a good outcome compared with IV tPA and with placebo. Harm
      may accrue to patients treated with IV-IA therapy who have an unfavorable
      baseline CT scan appearance. CONCLUSIONS: Patients with a favorable baseline CT
      scan appearance are the most likely to benefit from IV-IA therapy. This
      hypothesis will be tested in the IMS-3 study.

PMID- 16971598
TI  - Functional MR imaging of the human sensorimotor cortex after toe-to-finger
      transplantation.
AB  - BACKGROUND: A model of toe-to-finger transplantation has been used in studying
      peripheral nerve regeneration and central reorganization. It was found that
      recovery of sensory perception depends not only on peripheral reinnervation but
      also on central integrative mechanisms. OBJECTIVE: Our aim was to investigate
      functional changes of the brain and somatotopic representation of the
      transplanted toes after toe-to-finger transplantation. MATERIALS AND METHODS: Six
      patients who had toe-to-finger transplantation from 3 to 8 years earlier
      underwent motor and sensory functional MR imaging studies of transplanted toes
      and opposite corresponding normal fingers. The motor task was performed by
      repetitively tapping of the transplanted toe or finger against the thumb, whereas
      the sensory task was applied by tactilely stimulating the pulp of the
      transplanted toe or finger. RESULTS: The main activation areas from both types of
      stimulations were located in the expected location of the finger homunculus of
      the primary sensorimotor cortex. In addition, activated volumes from the
      transplanted toes were significantly greater than those from the opposite fingers
      (P = .017 for motor task and P = .005 for tactile sensory task, paired samples
      Student t test). CONCLUSIONS: Functional recruitment in the primary sensorimotor
      cortex seemed to have occurred following toe-to-finger transplantation. The
      transplanted toe was somatotopically represented in the hand area.

PMID- 16971599
TI  - Hippocampal atrophy confounds template-based functional MR imaging measures of
      hippocampal activation in patients with mild cognitive impairment.
AB  - BACKGROUND AND PURPOSE: Functional MR imaging has been used to study patterns of
      hippocampal activation that distinguish pathologic from normal memory loss in the
      elderly population. Our objective was to assess whether hippocampal atrophy
      confounds measurements of hippocampal activation in subjects with mild cognitive
      impairment (MCI). METHODS: Twenty subjects with MCI and 20 elderly control
      subjects with objectively normal memory were studied at 4T during a face-name
      paradigm designed to activate the hippocampus. Hippocampal activation was
      measured using 2 separate approaches: applying a preset region of interest (ROI)
      in standardized template space and applying a manually drawn ROI in native
      subject space. Pearson correlation coefficients were calculated to compare group
      dependent relationships between hippocampal volume and activation. Analysis of
      covariance (ANCOVA) was performed to assess group differences in hippocampal
      activation during encoding and retrieval. Age and hippocampal volume were
      included as covariates, as was a term for the interaction between hippocampal
      volume and group. RESULTS: When hippocampal activation was measured by the
      template-based method, the correlation coefficient in the right hippocampus of
      subjects with MCI but not control subjects during retrieval differed
      significantly from zero. There was a significant (P < .05) group-by-volume
      interaction in the ANCOVA model. No significant correlations or interactions were
      demonstrated when activation was measured in native subject space with manually
      drawn ROIs. CONCLUSION: Our findings suggest a potential confounding relationship
      between hippocampal volume and activation for subjects with MCI in template-based
      analyses. Template-based measures of hippocampal activation that do not
      adequately account for hippocampal atrophy should be used with caution in
      patients with MCI.

PMID- 16971600
TI  - Magnocellular and parvocellular visual pathways have different blood oxygen level
      dependent signal time courses in human primary visual cortex.
AB  - PURPOSE: The magnocellular and parvocellular pathways (M and P pathways) are the
      major pathways of the visual system, with distinct histologic and physiologic
      properties that may also have different metabolic characteristics. We hypothesize
      that the differences of the 2 visual pathways would also manifest as differences
      in the signal time course of blood oxygen level-dependent functional MR imaging
      (BOLD fMRI). The differences in BOLD signal time course may provide insight into
      the metabolic requirements of the 2 pathways. METHODS: Eleven fMRI sessions on 6
      subjects were performed using stimuli that preferentially activated the 2
      pathways. Regions commonly activated by both the M and P stimuli in the primary
      visual cortex (V1) were determined, and the contrast elicited by the stimulus,
      time-to-peak (TTP), and the full width at half maximum (FWHM) of the BOLD signal
      time course were measured. RESULTS: The functional stimuli activated cortical
      regions described previously in the literature, such as V1, V4, and V5. Within
      V1, the TTP of the signal time course of the 2 stimuli were statistically
      different, with the P stimulus generating TTPs that were on average 12% faster
      than the M stimulus (P = .0037). CONCLUSION: We have demonstrated the ability to
      functionally differentiate the M and P stimuli in a commonly activated anatomic
      region. Because the BOLD response is dependent on the ratio of oxyhemoglobin and
      deoxyhemoglobin in the blood, the difference in the BOLD time course between the
      2 stimuli suggests that the oxygen demand of the 2 pathways may be different.

PMID- 16971601
TI  - CT arteriography and venography in pulsatile tinnitus: preliminary results.
AB  - BACKGROUND AND PURPOSE: Pulsatile tinnitus (PT), a common disorder, can be caused
      by a variety of otologic and vascular lesions. Various imaging modalities,
      including CT, MR imaging and angiography, and conventional angiography, have been
      used in the assessment of PT. Ideally, a single imaging study to evaluate for the
      largest variety of etiologies would be optimal. In our study, we examine the
      potential for CT arteriography and venography (CTA/V) in the evaluation of PT.
      METHODS: Sixteen patients with PT were prospectively evaluated by an
      otolaryngologist, had a normal otologic examination, and were referred for a
      CTA/V. All examinations were performed on a 16-section multidetector CT. The
      carotid bifurcations, internal carotid artery course, transverse and sigmoid
      sinuses, jugular foramen, internal jugular vein, sella turcica, and temporal
      bones were evaluated. RESULTS: Seven of the 16 patients had lesions on CTA/V that
      could account for their PT. Examples of pathologic conditions in the series
      included a significantly dominant venous system, a venous diverticulum with
      stricture, and a transverse sinus stenosis. CONCLUSIONS: Preliminary findings
      indicate that CTA/V can be a valuable imaging tool in the assessment of PT. With
      this technique, arterial, venous, middle, and inner ear causes of PT can be
      excluded.

PMID- 16971602
TI  - Pituicytoma: diagnostic features on selective carotid angiography and MR imaging.
AB  - We report a case of pituicytoma, a rare primary tumor of the neurohypophysis. A
      64-year-old man presented with progressive visual complaints, bitemporal
      hemianopsia, and headache. Imaging studies revealed distinctive features of a
      mass lesion that thickened the pituitary stalk with a bilobed protrusion
      extending into the hypothalamus. Angiography demonstrated tumor vascular supply
      from the superior hypophyseal arteries representing the diencephalic branches of
      the internal carotid arteries. We discuss the imaging and pathology of this
      unusual tumor.

PMID- 16971603
TI  - CT assessment of vocal cord medialization.
AB  - BACKGROUND AND PURPOSE: Unilateral vocal cord paralysis (UVCP) occurs after
      iatrogenic injury or disease process and is associated with dysphonia and
      aspiration. Various surgical options are available for treatment of UVCP,
      including vocal cord medialization thyroplasty and injection laryngoplasty. These
      augmentative procedures improve phonation and airway protection. Our purpose was
      to demonstrate the CT appearance of implants used for the treatment of UVCP.
      METHODS: Twelve patients treated surgically for UVCP were studied with helical
      CT. The vocal cords were augmented by using Silastic implants (n = 7),
      polytetrafluoroethylene (Gore-Tex) implants (n = 2), Teflon injections (n = 2),
      or fat injection (n = 1). Augmented vocal cords were characterized by size,
      shape, and Hounsfield units (HU). Two other patients with failed medialization
      thyroplasty were evaluated for the position of the extruded implant relative to
      the paralyzed vocal cord. RESULTS: The 7 Silastic implants were triangular and
      hyperattenuated (293.4 +/- 90.4 HU). The 2 Gore-Tex implants were heterogeneous
      with lobulated medial margins and were hyperattenuating (320 and 414 HU). The
      injected materials demonstrated ovoid/masslike configurations: the 2 Teflon
      injections were hyperattenuated (107 and 429 HU), and the fat injection was
      hypoattenuated (-102 HU). Inferior displacement of the implant was demonstrated
      relative to the true vocal cord in 2 patients with failed Silastic thyroplasties.
      CONCLUSION: CT can distinguish various types of vocal cord augmentation. Silastic
      implants are recognized by their characteristic triangular configuration. The
      Gore-Tex implants had unique heterogeneous attenuation with lobulated medial
      margins. Fat and Teflon injections both appear ovoid/masslike. Teflon injection
      should not be mistaken for tumor.

PMID- 16971604
TI  - Percutaneous radio-frequency mandibular nerve rhizotomy guided by CT fluoroscopy.
AB  - We describe a new method for radio-frequency mandibular nerve rhizotomy under CT
      fluoroscopy. A patient with cancer had severe intractable and drug-resistant pain
      in his left mandibular region. Because he had an anatomic deformity due to cancer
      invasion and radiation therapy, we planned a mandibular nerve rhizotomy under CT
      fluoroscopic imaging. The needle was advanced to the mandibular nerve just caudal
      to the foramen ovale under real-time CT fluoroscopy, avoiding the cancer region.
      Pain scores of the patient were reduced after the nerve rhizotomy, without any
      complications.

PMID- 16971605
TI  - Palatal enlargement in chronic lymphocytic leukemia.
AB  - Palatal involvement in chronic lymphocytic leukemia (CLL) is rare and has only
      been reported 3 previous times in the non-radiology literature. To our knowledge
      this is the first imaging description of this entity. Based on our experience,
      when smoothly lobulated, homogeneous masses are identified on the oral surface of
      the hard palate, the diagnosis of CLL should be considered.

PMID- 16971606
TI  - CT and MR imaging of giant cell granuloma of the craniofacial bones.
AB  - BACKGROUND AND PURPOSE: Giant cell granuloma (GCG) is a rare lesion. The purpose
      of this study was to determine the CT characteristics and describe possible MR
      imaging features of GCG of the craniofacial bones. METHODS: We retrospectively
      reviewed 7 CT studies and 1 MR imaging study of 7 histologically proved cases of
      GCG in 2 men, 3 women, and 2 patients of unknown gender, aged 12-51 years, during
      a period of 10 years, from 1995 to 2005. RESULTS: The granulomas predominantly
      involved the maxilla in 3 patients, the mandible in 2 patients, the temporal bone
      in 1 patient, and the nasal cavity in 1 patient. These lesions on imaging were
      expansile masses that demonstrated adjacent bone wall thinning, and most were
      associated with lytic bone destruction. They were predominantly masses with soft
      tissue attenuation on CT scans and may have infiltrated the surrounding soft
      tissue structures. The patient with an MR imaging had a lesion that was
      hypointense on both T1- and T2-weighted MR images. The lesions revealed avid
      homogeneous contrast enhancement. CONCLUSION: The imaging features of GCG are
      nonspecific. However, this entity should be included in the differential
      diagnosis of expansile lesions in the craniofacial bones.

PMID- 16971607
TI  - Biopsy of deep-seated head and neck lesions under intraoral ultrasound guidance.
AB  - Although transcutaneous ultrasound combined with fine-needle aspiration is often
      used as initial modality for evaluating superficial neck masses, its role in
      management of deep-seated neck masses is limited. Intraoral ultrasound and guided
      biopsy helps in obtaining tissue from deep-seated neck masses for an accurate
      histologic diagnosis, providing useful information in treatment planning. This
      article discusses the role of intraoral ultrasound and presents 3 cases in which
      biopsy of deep-seated neck masses under intraoral ultrasound guidance helped in
      diagnosis and management.

PMID- 16971608
TI  - Imaging findings of a hibernoma of the neck.
AB  - Hibernoma is an uncommon benign fatty tumor that arises from the vestiges of
      fetal brown fat. We present a case report of a hibernoma of the neck in an
      asymptomatic 19-year-old girl and describe the important imaging findings.
      Computed tomography (CT) shows a well defined hypodense mass with septations.
      Magnetic resonance imaging (MRI) shows intermediate T1 and bright T2 signal of
      the mass and also demonstrates the characteristic marked contrast enhancement.

PMID- 16971609
TI  - Temporal giant cell reparative granuloma: a reappraisal of pathology and imaging
      features.
AB  - We report a case of large temporal giant cell reparative granuloma in a 72-year
      old man. MR imaging depicted a right temporal expansile multiloculated lesion,
      with hyper- and hypointense signal areas on T2-weighted images, heterogeneously
      enhancing after gadolinium administration. Cortical thinning and bone remodeling
      of the temporal squamous portion were better seen on CT. The patient underwent
      surgery, and the diagnosis was achieved by the correlation of imaging,
      histologic, and laboratory findings.

PMID- 16971610
TI  - Absent semicircular canals in CHARGE syndrome: radiologic spectrum of findings.
AB  - BACKGROUND AND PURPOSE: This paper describes the CT findings that characterize
      the middle and inner ear anomalies in coloboma, heart defects, choanal atresia,
      mental retardation, genitourinary, and ear anomalies (CHARGE) syndrome. With this
      information, neuroradiologists will be better prepared to provide clinically
      relevant information to their referring physicians regarding this rare syndrome.
      MATERIALS AND METHODS: CT studies from 13 patients were reviewed by 2
      neuroradiologists with Certificate of Additional Qualification. Each ear was
      counted separately for a total of 26 ears. Middle and inner ear anomalies
      associated with CHARGE syndrome were categorized. Investigational review board
      approval was obtained. RESULTS: Twenty of 26 (77%) ears demonstrated cochlear
      aperture atresia. Four of these ears were evaluated with MR imaging and were
      found to lack a cochlear nerve. Twenty-one of 26 (81%) cochlea had some form of
      dysplasia. Six of 26 (23%) round windows were aplastic. Three of 26 (12%) round
      windows were hypoplastic. Twenty-one of 26 (81%) oval windows were atretic or
      aplastic. Fifteen of 26 (58%) vestibules were hypoplastic or dysplastic. There
      were 5 of 26 (19%) enlarged vestibular aqueducts. Twelve of 26 (46%) vestibular
      aqueducts had an anomalous course. All cases demonstrated absent semicircular
      canals. Twenty-three of 26 (88%) facial nerve canals had an anomalous course.
      Four of 26 (15%) tympanic segments were prolapsed. Three of 26 (12%) temporal
      bones had an anomalous emissary vein referred to as a petrosquamosal sinus.
      Twenty-one of 26 (81%) middle ear cavities were small. Twenty-three of 26 (93%)
      ossicles were dysplastic with ankylosis. Three of 26 (12%) internal auditory
      canals were small. CONCLUSION: The CT findings that correlate to the anomalies of
      CHARGE syndrome affect conductive as well as sensorineural hearing. Stenosis of
      the aperture for the cochlear nerve aperture on CT is suggestive of hypoplasia or
      absence of the cochlear nerve, which has been demonstrated in some cases by MR.
      Absence of the cochlear nerve would be a contraindication to cochlear
      implantation.

PMID- 16971611
TI  - Anterior ethmoidal artery aneurysm and intracerebral hemorrhage.
AB  - The association between the formation of intracranial aneurysms and situations of
      increased blood flow in certain areas of the brain is well accepted today. It has
      been seen in association with arteriovenous malformations of the brain, carotid
      occlusion, and Moyamoya disease. The occurrence of aneurysms in small arteries of
      the skull base, with the exception of the intracavernous carotid artery, however,
      is rare. We report a case of a 55-year-old woman who presented with an
      intracerebral hemorrhage caused by a ruptured anterior ethmoidal artery aneurysm.
      To the best of our knowledge, this is only the second case of documented
      intracranial bleeding from such a lesion.

PMID- 16971612
TI  - Giant cell reparative granuloma of the sphenoid bone.
AB  - We present 2 patients with giant cell reparative granuloma (GCRG) of the sphenoid
      bone. The first patient is an 8-year-old boy with involvement of the greater
      wing, and the second is a 53- year-old man with a lateral pterygoid plate mass.
      Both patients presented with rapid expansion of lytic bone lesions, which had
      solid and cystic components and lacked matrix calcification. Biopsies were
      indeterminate for definitive diagnoses. The radiologic appearance, location, and
      incidence of the lesions, and the patient's age and medical history are helpful
      aids in narrowing the differential diagnosis of sphenoid bone lesions. However,
      the imaging and, occasionally, even the histologic findings may not suggest the
      specific diagnosis of GCRG, which must be added into the differential diagnosis
      of rapidly enlarging cystic bone lesions of the sphenoid bone.

PMID- 16971613
TI  - Procedural morbidity and mortality of elective coil treatment of unruptured
      intracranial aneurysms.
AB  - BACKGROUND AND PURPOSE: To report morbidity, mortality, and angiographic results
      of elective coiling of unruptured intracranial aneurysms. METHODS: In a 10-year
      period, 176 unruptured aneurysms in 149 patients were electively treated with
      detachable coils. Seventy-nine aneurysms were additional to another ruptured
      aneurysm but were coiled more than 3 months after subarachnoid hemorrhage, 59
      aneurysms were incidentally discovered, and 38 aneurysms presented with symptoms
      of mass effect. Mean size of the 176 unruptured aneurysms was 10.6 mm (median, 8
      mm; range, 2-55 mm). One hundred thirteen aneurysms (64%) were small (<10 mm), 44
      aneurysms (25%) were large (10-25 mm), and 19 aneurysms (11%) were giant (25-55
      mm). Thirty wide-necked aneurysms (17%) were coiled with the aid of a supporting
      device. RESULTS: Procedural mortality of coiling was 1.3% (2 of 149; 95%
      confidence interval [CI], 0.7-5.1%), and morbidity was 2.6% (4 of 149, 95% CI,
      0.8-7.0%). The 4 patients with permanent morbidity were independent (GOS 4).
      Initial aneurysm occlusion was complete (100%) in 132 aneurysms, nearly complete
      (90%-98%) in 36 aneurysms, and incomplete (60%-85%) in 8 aneurysms. Six-month
      follow-up angiography was available in 132 patients with 154 coiled aneurysms
      (87.5%); partial reopening occurred in 25, mainly large and giant aneurysms
      (16.2%). Additional coiling was performed in 22 aneurysms and additional parent
      vessel occlusion in 1 aneurysm. There were no complications of additional
      treatments. CONCLUSION: Elective coiling of unruptured intracranial aneurysms has
      low procedural mortality and morbidity. For the management of unruptured
      aneurysms, endovascular treatment should be considered.

PMID- 16971614
TI  - Can neck size in elastase-induced aneurysms be controlled? A retrospective study.
AB  - BACKGROUND AND PURPOSE: Reproducible animal models with appropriate neck size are
      crucial for preclinical assessment of aneurysm therapies. Our purpose was to
      determine whether the neck size of elastase-induced aneurysms could be controlled
      by adjusting the position of the temporary occlusion balloon. METHODS: Seventy
      two elastase-induced aneurysms in rabbits were retrospectively analyzed. Three
      groups (group 1, n = 35; group 2, n = 32; group 3, n = 5) were defined according
      to different balloon position (lowest, intermediate, and highest, respectively)
      related to the origin of right common carotid artery (CCA). Aneurysm sizes in
      different groups were measured and compared; parent artery dilation was assessed
      as present or absent. The Wilcoxon rank sum test, the Fisher exact test, and the
      chi(2) test were used for statistics process. RESULTS: The mean aneurysm neck
      diameter in group 1 was significantly wider than that in group 2 (P = .0001). The
      proportion of wide-necked (diameter of neck >4 mm) aneurysms in group 1 was
      significantly higher than that in group 2 (P = .0011). The mean dome/neck ratio
      in group 1 was smaller than that of group 2 (P = .0031). Aneurysm width and
      height and the frequency of parent artery dilation were not different in groups 1
      and 2 (P = .43, P = .10, and P = .25). No aneurysms formed in group 3.
      CONCLUSION: The neck size of elastase-induced aneurysms can be controlled by
      adjusting the position of the inflated balloon, with balloon positioning that
      bridges from the CCA to the subclavian/brachiocephalic arteries yielding narrow
      necked aneurysms.

PMID- 16971615
TI  - Giant and large peripheral cerebral aneurysms: etiopathologic considerations,
      endovascular treatment, and long-term follow-up.
AB  - BACKGROUND AND PURPOSE: Giant/large peripheral cerebral aneurysms beyond the
      circle of Willis and middle cerebral artery (MCA) bifurcation are rare lesions,
      their etiopathogenesis is not completely elucidated, and their treatment is often
      difficult. We reviewed the etiopathologic findings available in the literature
      and report the results and long-term follow-up in 10 patients with a giant/large
      peripheral aneurysm treated by parent artery occlusion. METHODS: Four aneurysms
      were on the MCA, 2 on the anterior cerebral artery, and 4 on the posterior
      cerebral artery (PCA). Two patients presented with bleeding. An occlusion test
      was performed in 7 patients. Occlusion of the parent artery was performed by
      using coils in 8 patients; and liquid coils and glue, in 2. Imaging follow-up was
      available from 1.5 to 4.5 years; and clinical outcome, from 1.5 to 7 years.
      RESULTS: All aneurysms were excluded. One patient developed a partial homonymous
      hemianopsia after PCA occlusion. A transient deficit was observed in 2 other
      patients. In the partially thrombosed aneurysms, follow-up imaging showed
      shrinkage of the thrombosed compartment of the aneurysm and disappearance of the
      mass effect. No patient experienced progression of symptoms and/or bleeding
      during the follow-up period. At long-term follow-up, 6 patients presented with a
      modified Rankin Scale score of 0; 3, with score of 1; and 1, with score of 2.
      CONCLUSION: The endovascular occlusion of the parent artery appears a relatively
      safe and efficacious technique in the treatment of these lesions. Long-term
      follow-up studies confirm persistent exclusion of the aneurysm and good clinical
      tolerance to the vessel occlusion.

PMID- 16971616
TI  - Endovascular treatment of intracranial aneurysms with matrix detachable coils:
      immediate posttreatment results from a prospective multicenter registry.
AB  - BACKGROUND AND PURPOSE: Endovascular treatment of intracranial aneurysms by using
      detachable coils has become an accepted alternative to surgery. To reduce the
      rate of aneurysm recanalization after treatment, biologically active
      polyglycolic/polylactic acid-covered platinum coils have been proposed. A
      prospective and multicenter registry was conducted in France to evaluate the
      safety and short-term and long-term efficacy of Matrix detachable coils. This
      first analysis is focused on the safety and short-term efficacy. METHODS: Two
      hundred sixty-one patients having ruptured or unruptured aneurysms treated via
      endovascular approach were included in this registry. Patients with giant
      aneurysms or in poor clinical condition (Glasgow Coma Scale < 10) were excluded.
      Because of various protocol violations, clinical analysis was conducted in 236
      patients having 244 aneurysms. Technical and clinical complications were
      systematically recorded. Angiographic analysis was performed by a core laboratory
      by using the Raymond Grading Scale on 224 patients having 232 aneurysms. RESULTS:
      Complete occlusion was achieved in 102 aneurysms (44.0%); neck remnant, in 58
      aneurysms (25.0%); and aneurysm remnant, in 72 aneurysms (31.0%). Technical and
      clinical complications related to the procedure were encountered in 43 patients
      (18.2%). Postoperative modification of the clinical status was observed in 12
      patients (5.1%). Two patients died (0.8%), 6 had a permanent deficit (2.5%), and
      4 had a transient deficit (1.7%). Treatment-related mortality was 0.8% and
      permanent morbidity was 2.5%. CONCLUSION: Endovascular treatment of intracranial
      aneurysms by using Matrix detachable coils is feasible and demonstrated initial
      angiographic results and overall morbidity and mortality rates that are within
      the ranges found in the literature in the use of bare platinum coils.

PMID- 16971617
TI  - Intra-arterial digital subtraction angiography through the ear artery for
      experimental aneurysm imaging.
AB  - Digital subtraction angiography through the central artery of the ear was
      performed to show elastase-induced aneurysms in 34 rabbits. Twenty-eight (82%)
      aneurysms in which common origins of the bilateral common carotid artery (CCA)
      were found were well shown. All 6 other aneurysms not well shown had separate
      origins of the CCAs from the aortic arch (P < .001). This method can be used for
      angiographic follow-up when there is a common origin of the CCAs.

PMID- 16971618
TI  - Computational fluid dynamics modeling of intracranial aneurysms: effects of
      parent artery segmentation on intra-aneurysmal hemodynamics.
AB  - PURPOSE: The purpose of this study is to show the influence of the upstream
      parent artery geometry on intraaneurysmal hemodynamics of cerebral aneurysms.
      METHODS: Patient-specific models of 4 cerebral aneurysms (1 posterior
      communicating artery [PcomA], 2 middle cerebral artery [MCA], and 1 anterior
      communicating artery [AcomA]) were constructed from 3D rotational angiography
      images. Two geometric models were constructed for each aneurysm. One model had
      the native parent vessel geometry; the second model was truncated approximately 1
      cm upstream from the aneurysm, and the parent artery replaced with a straight
      cylinder. Corresponding finite element grids were generated and computational
      fluid dynamics simulations were carried out under pulsatile flow conditions. The
      intra-aneurysmal flow patterns and wall shear stress (WSS) distributions were
      visualized and compared. RESULTS: Models using the truncated parent vessel
      underestimated the WSS in the aneurysms in all cases and shifted the impaction
      zone to the neck compared with the native geometry. These effects were more
      pronounced in the PcomA and AcomA aneurysms where upstream curvature was
      substantial. The MCA aneurysm with a long M1 segment was the least effected. The
      more laminar flow pattern within the parent vessel in truncated models resulted
      in a less complex intra-aneurysmal flow patterns with fewer vortices and less
      velocity at the dome. CONCLUSIONS: Failure to properly model the inflow stream
      contributed by the upstream parent artery can significantly influence the results
      of intra-aneurysmal hemodynamic models. The upstream portion of the parent vessel
      of cerebral aneurysms should be included to accurately represent the intra
      aneurysmal hemodynamics.

PMID- 16971619
TI  - Carotid-compression technique for the insertion of guiding catheters.
AB  - Inserting a guiding catheter into a tortuous artery for neurointerventional
      procedures can be difficult. In our technique, the carotid artery is manually
      compressed to stabilize and/or straighten the inserted wire before advancing the
      guiding catheter. Although this technique is not risk-free and care must be taken
      to avoid vascular injury by excessive compression, it is useful for the insertion
      of a guiding catheter into the carotid artery.

PMID- 16971620
TI  - Assessment of white matter damage in subacute sclerosing panencephalitis using
      quantitative diffusion tensor MR imaging.
AB  - BACKGROUND AND PURPOSE: Subacute sclerosing panencephalitis (SSPE), a rare
      progressive degenerative disease, is caused by persistent infection with a
      defective measles virus. The correlation between the clinical staging and MR
      imaging is usually poor. The aim of the study was to investigate the role of
      diffusion tensor imaging (DTI) in the early detection of white matter damage in
      SSPE in the presence of normal findings on conventional imaging. METHODS: DTI was
      performed in 21 patients in stage II SSPE and 10 age/sex-matched healthy
      controls. Fractional anisotropy (FA) and mean diffusivity (MD) values were
      calculated in the periventricular white matter, corpus callosum, and posterior
      limb of the internal capsule in patients with normal and abnormal findings on
      conventional imaging as well as healthy controls. RESULTS: The patients were
      grouped into those with normal (n = 11) and abnormal (n = 10) findings on
      conventional imaging for the purpose of quantitative DTI analysis. Abnormal- and
      normal-appearing white matter on T2-weighted images showed significantly
      decreased FA values in all the regions compared with those in healthy controls.
      MD values were significantly increased in the periventricular white matter region
      of the frontal and parietooccipital lobe in patients with normal as well as
      abnormal findings on conventional imaging compared with those in healthy
      controls. CONCLUSION: DTI detects early white matter abnormalities that may have
      significant therapeutic implication, even in the presence of normal findings on
      conventional imaging, in patients with SSPE.

PMID- 16971621
TI  - Diffusion tensor imaging in hydrocephalus: initial experience.
AB  - PURPOSE AND BACKGROUND: Diffusion tensor imaging (DTI) is an MR imaging-based
      technique that provides an in vivo tool for visualization of white matter tracts.
      In this preliminary study, we used this technique to investigate the diffusion
      characteristics of white matter tracts in patients with hydrocephalus before and
      after surgery and compared them with age-matched volunteers. MATERIALS AND
      METHODS: Seven patients with different types of acute hydrocephalus (defined by
      acute clinical signs of increased intracranial pressure and imaging evidence of
      enlarged ventricles) underwent MR imaging including a DTI protocol before and
      after surgery for shunt placement/revision or ventriculostomy. Eight age-matched
      healthy subjects served as a control group. The DTI was acquired in a clinical
      setting that included 6 gradient directions with a b value of 1000 s/mm(2).
      RESULTS: Before surgery, in fiber systems lateral to the ventricles (corona
      radiata), the diffusion parallel to the fibers was increased (+10%) and the
      diffusion perpendicular to the fibers was decreased (-25%) in all patients,
      resulting in an overall increase in the fractional diffusion anisotropy (FA,
      +28%). Following surgery, the FA values approached those of control values in all
      except 1 patient. In the corpus callosum, the presurgery FA values in patients
      with hydrocephalus (HCP) were lower than those of control values, and no
      significant changes were seen following surgery. CONCLUSIONS: DTI can distinguish
      the compression characteristics of white matter before and after surgery in
      patients with HCP. At the acute stage of the disease, DTI characteristics point
      to white matter compression as a possible cause of the observed changes.

PMID- 16971622
TI  - Subdural hematomas in infants with benign enlargement of the subarachnoid spaces
      are not pathognomonic for child abuse.
AB  - BACKGROUND AND PURPOSE: Patients who have benign enlargement of the subarachnoid
      spaces (BESS) have long been suspected of having an increased propensity for
      subdural hematomas either spontaneously or as a result of accidental injury.
      Subdural hematomas in infants are often equated with nonaccidental trauma (NAT).
      A better understanding of the clinical and imaging characteristics of subdural
      hematomas that occur either spontaneously or as a result of accidental trauma may
      help distinguish this group of patients from those who suffer subdural hematomas
      as a result of NAT. The purpose of this study is to describe the clinical and
      imaging characteristics of subdural hematomas that occur either spontaneously or
      as a result of accidental injury in infants with BESS. METHODS: We conducted a
      retrospective review of all patients with BESS complicated by subdural hematomas
      evaluated at a single institution from 1998 to 2004. Data concerning the
      patient's clinical presentation, physical findings, imaging, and management are
      described. RESULTS: During the study period, 7 patients with BESS complicated by
      subdural hematoma were identified. Their mean age at identification of the
      subdural hematoma was 7.4 months of age. In 5 cases, there was no recognized
      trauma before identification of the subdural hematoma. In 3 cases, baseline CT or
      MR imaging was available, showing prominent subarachnoid spaces without any
      evidence of subdural hemorrhage. CONCLUSION: Although suspicious for NAT,
      subdural hematomas can occur in children either spontaneously or as a result of
      accidental trauma. Caution must be exercised when investigating for NAT based on
      the sole presence of subdural hematomas, especially in children who are otherwise
      well and who have BESS.

PMID- 16971623
TI  - Parry-Romberg syndrome with a clinically silent white matter lesion.
AB  - We performed a detailed neuroimaging study in a patient with Parry-Romberg
      syndrome. Proton MR spectroscopy demonstrated normal spectral patterns, though
      conventional MR imaging revealed high-intensity areas in the entire white matter
      in the left hemisphere. Single-photon emission tomography showed increased
      perfusion in the cortex of the affected hemisphere. Pyramidal tracts and optic
      radiations were preserved on diffusion tensor tractography. We will correlate
      these neuroimaging findings with normal psychomotor development in our patient.

PMID- 16971624
TI  - Acute vertebral compression fractures in patients with multiple myeloma:
      evaluation of vertebral body edema patterns on MR imaging and the implications
      for vertebroplasty.
AB  - The presence of edema on MR imaging is a common finding in acute or subacute
      vertebral body compression fractures. Compression fractures can present in
      patients with benign osteoporosis, metastases, multiple myeloma, or hemangiomas.
      We present 2 patients with multiple myeloma who had symptomatic acute and
      subacute compression fractures documented on imaging studies without associated
      edema on MR imaging evaluation.

PMID- 16971625
TI  - A rare cause of flank mass: psoas abscess due to extensive primary thoracolumbar
      tuberculous spondylodiskitis.
AB  - Psoas abscess secondary to tuberculous spondylodiskitis is usually a complication
      of thoracolumbar vertebrae disease. The psoas abscess may be difficult clinically
      to diagnose because of its rarity, insidious onset of the disease, and
      nonspecific clinical presentation. We report multidetector CT and MR imaging
      findings of a psoas abscess secondary to primary tuberculous spondylodiskitis of
      the spine from the T3 to L2 vertebrae, which presented as a flank mass.

PMID- 16971626
TI  - Catheter-directed percutaneous transpedicular C2/C3 vertebroplasty in a patient
      with fibrous dysplasia using seldinger technique.
AB  - A 35-year-old man with polyostotic fibrous dysplasia and a massively enlarged
      skull presented with Lhermitte sensations due to an unstable, mulitseptated,
      lytic C2/3 vertebral body complex. Enlarged extracranial vasculature made open
      surgery a high-risk option and limited percutaneous access. A 5F catheter was
      directed by using a guidewire into the C2/C3 vertebral body complex via a
      transpedicularly placed biopsy cannula to ensure polymethylmethacrylate
      deposition throughout the lytic compartments of the vertebral body complex.

PMID- 16971627
TI  - Radiation exposure of patients in comprehensive computed tomography of the head
      in acute stroke.
AB  - BACKGROUND AND PURPOSE: To assess patient radiation exposure in comprehensive
      stroke imaging using multidetector row CT (MDCT) combining standard CT of the
      head, cerebral perfusion (CTP), and CT angiography (CTA) studies. METHODS:
      Examination protocols for CT and CTA of cerebral and cervical vessels, as well as
      CTP were simulated using a Somatom Sensation Cardiac 64. Effective doses were
      derived from measurements with the use of lithium-fluoride thermoluminescent
      dosimeters (LiF-TLD) at several organ sites using an Alderson-Rando phantom.
      RESULTS: LiF-TLD measurements resulted in effective doses of 1.7 mSv for CT, 1.9
      mSv for CTA of intracranial vessels, and 2.8 mSv for CTA of cervical vessels,
      respectively. Depending on examination parameters, effective doses varied between
      1.1 and 5.0 mSv for cerebral CTP. For CTP, local doses in the area of the primary
      beam ranged between 114 and 444 mGy. CONCLUSIONS: Comprehensive stroke imaging
      may result in up to 9.5 mSv with possible local doses of 490 mGy. Although
      critical doses for organ damage (eg, cataract formation or hair loss) are not
      reached, physicians need to be aware of possible radiation induced sequelae
      particularly in repetitive examinations.

PMID- 16971628
TI  - From flatland to the fourth dimension.

PMID- 16971629
TI  - MR imaging anatomy in neurodegeneration: a robust volumetric parcellation method
      of the frontal lobe gyri with quantitative validation in patients with dementia.
AB  - BACKGROUND AND PURPOSE: Brain volumetry is widely used for evaluating tissue
      degeneration; however, the parcellation methods are rarely validated and use
      arbitrary planes to mark boundaries of brain regions. The goal of this study was
      to develop, validate, and apply an MR imaging tracing method for the parcellation
      of 3 major gyri of the frontal lobe, which uses only local landmarks intrinsic to
      the structures of interest, without the need for global reorientation or the use
      of dividing planes or lines. METHODS: Studies were performed on 25 subjects-
      healthy controls and subjects diagnosed with Lewy body dementia and Alzheimer
      disease--with significant variation in the underlying gyral anatomy and state of
      atrophy. The protocol was evaluated by using multiple observers tracing scans of
      subjects diagnosed with neurodegenerative disease and those aging normally, and
      the results were compared by spatial overlap agreement. To confirm the results,
      observers marked the same locations in different brains. We illustrated the
      variabilities of the key boundaries that pose the greatest challenge to defining
      consistent parcellations across subjects. RESULTS: The resulting gyral volumes
      were evaluated, and their consistency across raters was used as an additional
      assessment of the validity of our marking method. The agreement on a scale of 0-1
      was found to be 0.83 spatial and 0.90 volumetric for the same rater and 0.85
      spatial and 0.90 volumetric for 2 different raters. The results revealed that the
      protocol remained consistent across different neurodegenerative conditions.
      CONCLUSION: Our method provides a simple and reliable way for the volumetric
      evaluation of frontal lobe neurodegeneration and can be used as a resource for
      larger comparative studies as well as a validation procedure of automated
      algorithms.

PMID- 16971630
TI  - Creutzfeldt-jakob disease involvement of rolandic cortex: a quantitative apparent
      diffusion coefficient evaluation.
AB  - BACKGROUND: Previous reports have suggested that abnormally reduced water
      diffusivity and T2 prolongation involving cerebral gray matter in patients with
      early sporadic Creutzfeldt-Jakob disease (sCJD) involves all areas of neocortex
      with similar frequency, except for primary sensorimotor cortex (Rolandic cortex)
      and visual cortex. Rolandic cortex often appears to be spared even in the
      presence of extensive surrounding neocortical signal intensity abnormality in
      adjacent frontal and parietal gray matter. A quantitative apparent diffusion
      coefficient (ADC) analysis was designed to investigate whether this unusual
      pattern results from pathophysiologic sparing of Rolandic cortex or from reduced
      conspicuity of signal intensity abnormality on MR imaging echo-planar diffusion
      weighted images (epiDWI) related to unknown underlying features of Rolandic
      cortex. METHODS: ADC maps were derived from epiDWI of 6 patients with sCJD and 8
      control patients. Bilateral regions of interest were manually selected in
      precentral gyri, superior frontal gyri, postcentral gyri, supramarginal gyri,
      thalamus, putamen, and caudate nuclei. ADC and relative ADC (rADC) values were
      calculated for each region of interest. RESULTS: Patients with CJD had
      significantly lower ADC values than control patients in all areas (P < or =
      0.05). The trend toward decreased ADC values in the deep nuclei correlates well
      with previously published reports. rADC were not significantly different between
      CJD and control groups in any area (P > 0.25 in all cases). CONCLUSION:
      Quantitative ADC measurements in patients with early sCJD demonstrate a similar
      degree of reduced water diffusivity in the primary somatosensory cortex as in
      other neocortical areas, despite the normal appearance of these areas on visual
      inspection of epiDWI.

PMID- 16971631
TI  - Reversible reduction of apparent diffusion coefficient values in bilateral
      internal capsules in transient hypoglycemia-induced hemiparesis.
AB  - A woman aged 68 years who experienced recurrent right hemiparesis caused by
      hypoglycemia was admitted to our hospital. When she was experiencing a low level
      of glucose, diffusion-weighted MR imaging showed the presence of hyperintensity
      lesions in the bilateral internal capsule. Diffusion-weighted MR imaging has been
      infrequently performed in patients with hypoglycemia. We report the reversible
      hyperintensity lesions on diffusion-weighted MR imaging in a hypoglycemic period
      in a patient with reversible hemiparesis. A reduction of apparent diffusion
      coefficient in a hypoglycemic period was clearly shown.

PMID- 16971632
TI  - Reversible delayed posthypoxic leukoencephalopathy.
AB  - Hypoxic ischemic encephalopathy may cause early deep white matter abnormalities
      on MR imaging that usually progress to include gray matter and basal ganglia
      change. Toxic leukoencephalopathy due to heroin inhalation predominantly causes
      cerebellar and posterior cerebral radiologic change. Both conditions rarely
      present clinically and radiologically in a delayed manner with subsequent
      recovery. We report a case of reversible delayed posthypoxic/toxic
      leukoencephalopathy with no clinical or radiologic evidence of gray matter
      insult.

PMID- 16971633
TI  - Extent of preoperative abnormalities and focus lateralization predict
      postoperative normalization of contralateral 1H-magnetic resonance spectroscopy
      metabolite levels in patients with temporal lobe epilepsy.
AB  - BACKGROUND AND PURPOSE: Magnetic resonance (MR) spectroscopy can be used to
      determine the side of seizure onset in patients with temporal lobe epilepsy. Some
      patients with abnormal MR spectroscopy findings also have contralateral
      abnormalities, which in some cases have been reported to normalize after temporal
      lobe resection. With the aim of better understanding the mechanisms underlying
      abnormal MR spectroscopy findings, the current study was performed to define
      patient features that would predict this postoperative normalization. METHODS:
      Fifteen patients with temporal lobe epilepsy were subjected to preoperative and
      postoperative 1H-MR spectroscopy investigations, and the preoperative and
      postoperative metabolite levels in the contralateral hippocampus and
      contralateral lateral temporal lobe (CLTL) were determined. RESULTS: In the CLTL,
      postoperative normalization was more pronounced for patients showing extensive
      preoperative ipsilateral and contralateral abnormalities on MR spectroscopy. A
      second factor that influenced the degree to which the metabolite levels changed
      postoperatively was the focus lateralization. Surgery tended to have a more
      pronounced effect on the contralateral metabolite levels in patients with a right
      temporal focus, whereas in patients with left temporal foci, postoperative
      metabolite levels were virtually unchanged. In the contralateral hippocampal
      region, neither preoperative abnormalities nor focus side was related to
      postoperative normalization. CONCLUSIONS: We have thus identified 2 different
      factors (widespread preoperative MR spectroscopy abnormalities and right-sided
      focus) that predict postoperative normalization of contralateral MR spectroscopy
      abnormalities. We suggest that both factors indicate a more generalized epileptic
      disease (ie, that the patients in whom the MR spectroscopy abnormalities
      normalize are recovering from a more severe impairment).

PMID- 16971634
TI  - Relationship between variations in the circle of Willis and flow rates in
      internal carotid and basilar arteries determined by means of magnetic resonance
      imaging with semiautomated lumen segmentation: reference data from 125 healthy
      volunteers.
AB  - BACKGROUND AND PURPOSE: Volume flow rates in the feeding arteries of the brain
      are measured to evaluate blood flow dynamics in vascular disease. Although these
      flow values are thought to be effected by anatomic variations in the circle of
      Willis, few reports have described the effect. This study reports on the
      relationship between variations in the circle of Willis and volume flow rates in
      the bilateral internal carotid and basilar arteries of normal volunteers.
      METHODS: We prospectively examined 125 healthy volunteers by MR imaging.
      Variations in the circle of Willis were classified as "textbook" type, hypoplasia
      of the precommunicating segment of the anterior cerebral artery (A1), hypoplasia
      of the precommunicating segment of the posterior cerebral artery (P1), or
      "other." Volume flow rates were measured by 2D cine phase-contrast MR imaging.
      Lumen boundaries and volume flow rates were semiautomatically determined by
      pulsatility-based segmentation. RESULTS: Of the 117 subjects (61 men, 56 women;
      mean age, 23.6 years) considered suitable for flow measurement, 105 showed
      textbook type, and 6 each showed A1 hypoplasia and P1 hypoplasia. Total flow
      rates for the 3 variations were 781 +/- 151 mL/min (mean +/- SD), 744 +/- 119,
      and 763 +/- 129, respectively. Relative contributions by flow rates of the
      internal carotid arteries and the basilar artery for the 3 variations were
      39.8%:38.9%:21.3%, 31.8%:49.1%:19.0%, and 46.6%:41.6%:11.7%, respectively,
      showing statistically significant differences. CONCLUSIONS: Variations in the
      circle of Willis correlate significantly with relative contributions by the flow
      rates of the bilateral internal carotid and basilar arteries.

PMID- 16971635
TI  - Effects of number of diffusion gradient directions on derived diffusion tensor
      imaging indices in human brain.
AB  - BACKGROUND AND PURPOSE: The effects of a number of diffusion-encoding gradient
      directions (NDGD) on diffusion tensor imaging (DTI) indices have been studied
      previously with theoretic analysis and numeric simulations. In this study, we
      made in vivo measurements in the human brain to compare different clinical scan
      protocols and to evaluate their effects on the calculated DTI indices. METHODS:
      Fifteen healthy volunteers were scanned with a 1.5T MR scanner. Single-shot DTI
      images were acquired using 3 protocols different in NDGD and number of
      excitations (NEX) for each direction (NDGD/NEX = 6/10, 21/3, 31/2). Means and
      standard error of mean (SEM) were calculated and compared in 6 regions of
      interest (ROIs) for mean diffusivity (D), fractional anisotropy (FA), diffusion
      tensor eigenvalues (lambda(1), lambda(2), and lambda(3)), and correlation
      coefficients (r) of these indices among the 3 DTI protocols. RESULTS: At the ROI
      level, no significant differences were found for the mean and SEM of D and FA
      among protocols (P > .05). The 6-NDGD protocol, however, yielded higher values
      for lambda(1) and lambda(2) and lower values for lambda(3) in most ROIs (P < .05)
      compared with the other protocols. At the voxel level, the correlation between
      the protocols r(21-31) were higher than r(6-21) and r(6-31) in most ROIs. The
      correlation of FA among 3 protocols also increased with increasing anisotropy.
      CONCLUSION: For ROI analyses, different NDGDs lead to similar values of FA and D
      but different eigenvalues. However, different NDGDs at the voxel level provide
      varying values. The selection of the NDGD, therefore, should depend on the focus
      of different DTI applications.

PMID- 16971636
TI  - Do transient ischemic attacks with diffusion-weighted imaging abnormalities
      correspond to brain infarctions?
AB  - BACKGROUND AND PURPOSE: Our aim was to determine whether diffusion-weighted
      imaging (DWI) changes associated with transient ischemic attack (TIA) are
      reversible or correspond to permanent tissue injury. METHODS: Among 103
      consecutive patients admitted for TIA, 36 (34.9%) had abnormalities on initial
      DWI (delay from TIA = 30 +/- 33 hours [mean +/- SD]). Thirty-three patients (59
      DWI lesions) had an MR imaging follow-up (delay from TIA = 10.6 +/- 5 months)
      including fluid-attenuated inversion recovery, T2, DWI, and 3D T1-weighted
      sequences. For each lesion, we recorded the quantitative parameters on initial
      DWI (volume, apparent diffusion coefficient [ADC]) and performed a comparison
      between reversible and irreversible lesions. RESULTS: MR imaging failed to detect
      any permanent injury in 7 patients and identified subsequent infarct in regions
      corresponding to the original DWI abnormalities in 26 patients (79%). Of the 59
      lesions initially identified on DWI, 45 (76.3%) were associated with permanent
      injury on follow-up MR imaging. The DWI volume was significantly larger (0.91 +/-
      1.7 versus 0.21 +/- 0.21 cm(3), P = .003) and the ADC ratio values lower (79 +/-
      15% versus 91 +/- 9%, P = .001) in lesions with subsequent infarct than in those
      that were fully reversible. CONCLUSION: By showing that most patients with DWI
      positive TIAs share the same imaging outcome as stroke patients, our data provide
      additional support for the redefinition of TIA, which considers that all cases of
      transient deficit with characteristic neuroimaging abnormalities should be
      diagnosed as a stroke.

PMID- 16971637
TI  - First results in an MR imaging--compatible canine model of acute stroke.
AB  - BACKGROUND AND PURPOSE: The purpose of this work was to develop an MR imaging
      compatible animal model of reversible embolic stroke. We hypothesize that real
      time MR imaging of the brain can be performed during stroke thrombolysis and can
      provide real-time feedback and guidance on the success of thrombolysis. METHODS:
      Embolic strokes were induced in 5 adult dogs by the use of autologous blood
      clots, with a sixth dog serving as an experimental control. Serial MR anatomic
      and physiologic imaging was performed to track the evolution of the stroke. The
      apparent diffusion coefficient (ADC) and quantitative cerebral blood flow (qCBF)
      were compared in the normal and stroke regions. During and after the
      administration of a chemical thrombolytic agent, MR imaging was performed to
      assess the outcome of the treatment. RESULTS: Strokes were successfully created
      in 5 animals. No ADC or qCBF changes were observed in the control animal. Both
      ADC and qCBF values were found to be significantly different in the region
      affected by the stroke. Restoration of flow was observed in 1 case. CONCLUSION:
      We have successfully implemented an MR imaging-compatible canine model of
      reversible embolic stroke.

PMID- 16971638
TI  - Does high-field MR imaging have an influence on the classification of patients
      with clinically isolated syndromes according to current diagnostic mr imaging
      criteria for multiple sclerosis?
AB  - BACKGROUND AND PURPOSE: Current MR imaging criteria for multiple sclerosis (MS)
      do not specify the magnetic field strength. The aim of this study was to
      investigate whether different MR imaging field strengths, specifically high-field
      MR imaging, have an impact on the classification of patients with clinically
      isolated syndromes suggestive of MS, according to MR imaging and diagnostic
      criteria. METHODS: In a prospective intraindividual comparative study, we
      examined 40 patients with clinically isolated syndromes (CIS) consecutively with
      a 1.5 T and 3T MR imaging system, including axial sections of T2 turbo spin-echo,
      fluid-attenuated inversion recovery, and T1 spin-echo, before and after injection
      of gadolinium-diethylene-triaminepentaacetic acid. Constant resolution parameters
      were used for both field strengths. High-signal-intensity white matter lesions
      with a size of >3 mm were counted and categorized according to their anatomic
      location in infratentorial, callosal, juxtacortical, periventricular, and other
      white matter areas. Assessment of the fulfilled Barkhof MR imaging and McDonald
      diagnostic criteria was made separately for both field strengths in every
      patient. RESULTS: Eleven patients fulfilled more MR imaging criteria at 3T. Two
      of these patients fulfilled the criterion of dissemination in space (DIS)
      according to the first definition of McDonald criteria, which is based on imaging
      criteria alone. Another patient had DIS only at 3T, according to the second
      definition of the McDonald criteria including CSF parameters. CONCLUSION: MR
      field strength, specifically high-field MR imaging, has a substantial influence
      on the classification of patients with CIS according to imaging and a mild
      influence on the classification according diagnostic criteria for MS, leading to
      consequences for prognostic classification, imaging guidelines, and clinical
      trials.

PMID- 16971639
TI  - Molecular characterization of disease-associated streptococci of the mitis group
      that are optochin susceptible.
AB  - Eight optochin-susceptible (Opt(s)) alpha-hemolytic (viridans) streptococcus
      isolates were characterized at the molecular level. These isolates showed
      phenotypic characteristics typical of both viridans streptococci and
      Streptococcus pneumoniae. Comparison of the sequence of housekeeping genes from
      these isolates with those of S. pneumoniae, Streptococcus mitis, Streptococcus
      oralis, and Streptococcus pseudopneumoniae suggested that the Opt(s) isolates
      corresponded to streptococci of the mitis group. Besides, the Opt(s) streptococci
      were negative by a Gen-Probe AccuProbe pneumococcus test and hybridized with
      specific pneumococcal probes (lytA and ply) but also with ant, a gene not present
      in most S. pneumoniae strains. Moreover, the isolates were insoluble in 1% sodium
      deoxycholate but completely dissolved in 0.1% deoxycholate. Sequence analysis of
      the lytA gene revealed that the Opt(s) streptococci carried lytA alleles
      characteristic of those present in nonpneumococcal streptococci of the mitis
      group. The determination of the partial nucleotide sequence embracing the atp
      operon encoding the F(o)F(1) H(+)-ATPase indicated that the optochin
      susceptibility of the isolates was due to the acquisition of atpC, atpA, and part
      of atpB from S. pneumoniae by horizontal gene transfer.

PMID- 16971640
TI  - Comparison of a PCR-restriction fragment length polymorphism (PCR-RFLP) assay to
      pulsed-field gel electrophoresis to determine the effect of repeated subculture
      and prolonged storage on RFLP patterns of Shiga toxin-producing Escherichia coli
      O157:H7.
AB  - In this study, we compared a recently developed PCR-restriction fragment length
      polymorphism (PCR-RFLP) assay with pulsed-field gel electrophoresis (PFGE) using
      three different Shiga toxin-producing Escherichia coli (STEC) strains to
      understand whether repeated subculture in vitro and prolonged storage at room
      temperature affect the RFLP patterns of STEC. The PFGE profiles of the STEC
      strains changed by 1 to 8 fragments after repeated subculture and prolonged
      storage; one strain was no longer clonal after repeated subculture compared to
      the original isolate according to the Tenover criteria. In contrast, RFLP
      patterns obtained by PCR-RFLP were identical after repeated subculture and
      prolonged storage. These data clearly indicate that the PCR-RFLP assay which is
      based on the diversity of region V, a regulatory region of Stx-phage, was not
      affected by repeated subculture and prolonged storage and is a more practical and
      reliable method for molecular typing of STEC strains.

PMID- 16971641
TI  - Effects of Bifidobacterium lactis Bb12 supplementation on intestinal microbiota
      of preterm infants: a double-blind, placebo-controlled, randomized study.
AB  - The gastrointestinal microbiota of preterm infants in a neonatal intensive care
      unit differs from that of term infants. In particular, the colonization of
      preterm infants by bifidobacteria is delayed. A double-blind, placebo-controlled,
      randomized clinical study was performed on 69 preterm infants to investigate the
      role of Bifidobacterium lactis Bb12 supplementation in modifying the gut
      microbiota. Both culture-dependent and culture-independent approaches were used
      to study the gut microbiota. Bifidobacterial numbers, determined by fluorescence
      in situ hybridization, were significantly higher in the probiotic than in the
      placebo group (log(10) values per g of fecal wet weight: probiotic, 8.18 + 0.54
      [standard error of the mean]; placebo, 4.82 + 0.51; P < 0.001). A similar trend
      for bifidobacterial numbers was also obtained with the culture-dependent method.
      The infants supplemented with Bb12 also had lower viable counts of
      Enterobacteriaceae (log(10) values of CFU per g of fecal wet weight: probiotic,
      7.80 + 0.34; placebo, 9.03 + 0.35; P = 0.015) and Clostridium spp. (probiotic,
      4.89 + 0.30; placebo, 5.99 + 0.32; P = 0.014) than the infants in the placebo
      group. Supplementation of B. lactis Bb12 did not reduce the colonization by
      antibiotic-resistant organisms in the study population. However, the probiotic
      supplementation increased the cell counts of bifidobacteria and reduced the cell
      counts of enterobacteria and clostridia.

PMID- 16971643
TI  - Susceptibilities of Propionibacterium acnes ophthalmic isolates to ertapenem,
      meropenem, and cefepime.
AB  - We investigated the in vitro susceptibilities of 23 Propionibacterium acnes
      ophthalmic isolates to ertapenem, meropenem, and cefepime by utilizing the Etest.
      The MICs ranged from 0.094 microg/ml to 0.75 microg/ml, 0.094 microg/ml to 1.5
      microg/ml, and 1 microg/ml to 12 microg/ml for ertapenem, meropenem, and
      cefepime, respectively. Based on our excellent in vitro carbapenem susceptibility
      results, in vivo studies using ertapenem and meropenem in a rabbit model of P.
      acnes endophthalmitis are warranted.

PMID- 16971642
TI  - Identification of Clostridium species and DNA fingerprinting of Clostridium
      perfringens by amplified fragment length polymorphism analysis.
AB  - An amplified fragment length polymorphism (AFLP) method was applied to 129
      strains representing 24 different Clostridium species, with special emphasis on
      pathogenic clostridia of medical or veterinary interest, to assess the potential
      of AFLP for identification of clostridia. In addition, the ability of the same
      AFLP protocol to type clostridia at the strain level was assessed by focusing on
      Clostridium perfringens strains. All strains were typeable by AFLP, so the method
      seemed to overcome the problem of extracellular DNase production. AFLP
      differentiated all Clostridium species tested, except for Clostridium ramosum and
      Clostridium limosum, which clustered together with a 45% similarity level. Other
      Clostridium species were divided into species-specific clusters or occupied
      separate positions. Wide genetic diversity was observed among Clostridium
      botulinum strains, which were divided into seven species-specific clusters. The
      same AFLP protocol was also suitable for typing C. perfringens at the strain
      level. A total of 29 different AFLP types were identified for 37 strains of C.
      perfringens; strains initially originating from the same isolate showed identical
      fingerprinting patterns and were distinguished from unrelated strains. AFLP
      proved to be a highly reproducible, easy-to-perform, and relatively fast method
      which enables high throughput of samples and can serve in the generation of
      identification libraries. These results indicate that the AFLP method provides a
      promising tool for the identification and characterization of Clostridium
      species.

PMID- 16971644
TI  - First reported case of dialysis-related peritonitis due to Escherichia vulneris.
AB  - Escherichia vulneris is a recently identified environmental organism that can
      colonize humans and animals. To date, very few infections with E. vulneris have
      been reported. This is the first reported case of peritonitis due to E. vulneris
      in the setting of peritoneal dialysis.

PMID- 16971645
TI  - Performance of rapid streptococcal antigen testing varies by personnel.
AB  - Rapid carbohydrate antigen tests are frequently used to diagnose group A
      streptococcal (GAS) pharyngitis. Despite evidence of modest sensitivity in
      medical settings, rapid antigen tests are available to the public for self
      testing. We sought to determine if the personnel performing a rapid streptococcal
      antigen test influence the test's performance characteristics. Throat swabs of
      pediatric patients performed for GAS pharyngitis in a tertiary-care children's
      hospital network were included during two study periods in 2004 and 2005. The
      performance characteristics of a rapid carbohydrate antigen test were evaluated
      in three clinical settings against a nucleic acid probe test method according to
      the personnel performing the test (laboratory technologist versus nonlaboratory
      personnel). Between the study periods, nonlaboratory personnel from one site
      underwent retraining. Subsequently, the performance characteristics of the rapid
      antigen test were reassessed. The sensitivity of the rapid antigen test varied
      widely among the different testing sites (56 to 90%). Notably, test sensitivity
      was consistently greater when the test was performed by laboratory technologists
      than when it was performed by nonlaboratory personnel (P < 0.0001). Although the
      rapid antigen test sensitivity significantly improved after nonlaboratory
      personnel at one testing site were retrained (sensitivity before versus after
      retraining; P < 0.0001), the sensitivity remained greater in the laboratory
      technologist cohort (P < 0.0001). These data confirm the important relationship
      of the operator performing a rapid streptococcal antigen test with the test's
      accuracy, even in a clinical setting, where operator training is mandated.
      Therefore, its use outside the medical setting by lay persons cannot be
      recommended without culture backup.

PMID- 16971646
TI  - Methods for detection of Trichomonas vaginalis in the male partners of infected
      women: implications for control of trichomoniasis.
AB  - Trichomonas vaginalis infection in men is an important cause of nongonococcal
      urethritis. Effective detection of the parasite in men using culture requires
      examination of multiple specimens. We compared culture and PCR-enzyme-linked
      immunosorbent assay in urethral swabs, urine, and semen for T. vaginalis
      detection in male sexual partners of women with trichomoniasis identified by wet
      mount and culture. Trichomonads were detected by at least one positive test in
      205/280 men (73.2%) who submitted at least one specimen for culture and PCR.
      Whereas InPouch TV culture detected only 46/205 cases (22.5%), PCR detected
      201/205 (98.0%). Urethral swab cultures from men with urethritis were more likely
      to be positive with shorter incubation than specimens from men without
      urethritis. T. vaginalis was detected more often in men with wet-mount-positive
      partners. Even with a sensitive PCR assay, reliable detection of T. vaginalis in
      male partners required multiple specimens. The majority of male sexual partners
      in this study were infected, emphasizing the importance of partner evaluation and
      treatment.

PMID- 16971647
TI  - Molecular characterization of Cryptosporidium spp. from children in Kolkata,
      India.
AB  - The intracellular parasite Cryptosporidium is responsible for severe diarrhea in
      immunocompromised persons in developing countries. Few studies on the
      characterization of the parasite in India are available. In this study, molecular
      characterization of the parasite from diarrheic children was carried out by PCR
      restriction fragment length polymorphism analysis. At least three genotypes were
      identified. Out of 40 positive samples, 35 were positive for C. hominis, 4 were
      positive for C. parvum, and 1 was positive for C. felis. This study clearly
      suggests that cryptosporidiosis in this region is caused largely by anthroponotic
      transmission.

PMID- 16971648
TI  - Molecular epidemiology of drug-resistant tuberculosis in Hungary.
AB  - Sixty-eight drug-resistant Mycobacterium tuberculosis isolates (44.2% of all
      resistant cases) were analyzed by IS6110 restriction fragment length polymorphism
      fingerprinting and spoligotyping to provide a deeper insight into the status of
      drug-resistant tuberculosis in Hungary. A total of 54.4% of the drug-resistant
      cases and 75% of the multidrug-resistant cases could be clustered. Analysis of
      the spoligotyping patterns of the strains revealed a high rate (66.2%) of
      infection by the Haarlem genotype, while none of the patients were infected by
      the Beijing genotype. The magnitude and the dynamics of drug-resistant
      tuberculosis are underestimated in Hungary.

PMID- 16971649
TI  - In vitro antifungal-drug susceptibilities of mycelial and yeast forms of
      Penicillium marneffei isolates in Cambodia.
AB  - Penicillium marneffei infection is an important disease among human
      immunodeficiency virus patients in Southeast Asia. The in vitro antifungal-drug
      susceptibilities of 29 clinical isolates and 5 isolates from bamboo rats
      collected from 2002 to 2004 were determined. The P. marneffei yeast form is more
      susceptible than the mycelial form to amphotericin B and ketoconazole, while the
      mycelial and yeast forms displayed similar susceptibilities to flucytosine and
      itraconazole. The MICs of fluconazole were higher for both mycelial and yeast
      forms.

PMID- 16971650
TI  - Beijing genotype of Mycobacterium tuberculosis is significantly associated with
      human immunodeficiency virus infection and multidrug resistance in cases of
      tuberculous meningitis.
AB  - Multidrug-resistant tuberculous meningitis is fatal without rapid diagnosis and
      use of second-line therapy. It is more common in human immunodeficiency virus
      (HIV)-positive patients. Beijing genotype strains of Mycobacterium tuberculosis
      are associated with drug resistance, particularly multidrug resistance, and their
      prevalence is increasing worldwide. The prevalence of Beijing genotype strains
      among Mycobacterium tuberculosis isolates from the cerebrospinal fluid of HIV
      positive (n = 35) and HIV-negative (n = 187) patients in Ho Chi Minh City was
      determined. The Beijing genotype was significantly associated with HIV status
      (odds ratio [OR] = 2.95 [95% confidence interval {CI}, 1.38 to 6.44]; P = 0.016),
      resistance to any drug (OR = 3.34 [95% CI, 1.87 to 5.95]; P < 0.001) and
      multidrug resistance (Fisher's exact test; P = 0.001). The association of the
      Beijing genotype with drug resistance was independent of HIV status. This is the
      first report of Beijing genotype association with HIV status, which may be an
      association unique to tuberculous meningitis.

PMID- 16971651
TI  - Lymphogranuloma venereum prevalence in Sweden among men who have sex with men and
      characterization of Chlamydia trachomatis ompA genotypes.
AB  - An outbreak of lymphogranuloma venereum (LGV) infections has recently been
      reported from The Netherlands and other European countries. The Swedish
      surveillance system has identified three LGV cases since 2004, all with
      clinically suspected infection in men who have sex with men (MSM). In order to
      assess the prevalence of LGV in a high-risk group of MSM and include clinically
      atypical cases, retrospective analysis of 197 Chlamydia trachomatis-infected men
      was performed. Sequencing of the ompA gene showed a different serotype
      distribution compared to recent Swedish studies in heterosexual populations. The
      most common types were G (45%), D (27%), and J (26%), whereas the normally
      predominant type E accounted for only 4% of the chlamydia cases. Furthermore,
      certain ompA genotype variants of the dominant serotypes were highly prevalent
      among MSM, and the reason for this is discussed. No additional case of LGV was
      detected by retrospective analysis of the high-risk MSM population. This
      indicates that, thus far, LGV in Sweden is only a result of sporadic import from
      infected MSM clusters abroad.

PMID- 16971652
TI  - Pilot study of a commercialized human papillomavirus (HPV) genotyping assay:
      comparison of HPV risk group to cytology and histology.
AB  - We evaluated a commercialized PCR assay, Linear Array, that detects 37 human
      papillomavirus (HPV) genotypes, using a sample of liquid cytology specimens (n =
      534). We found a strong association of an increasing level of HPV risk (HPV type
      16 [HPV16] > HPV18 > other carcinogenic types > noncarcinogenic types > negative
      specimens) with increasing severities of cytologic interpretations (P(Trend) <
      0.0005) and histologic diagnoses (P(Trend) < 0.0005).

PMID- 16971653
TI  - First detection of the Ambler class C 1 AmpC beta-lactamase in Citrobacter
      freundii by a new, simple double-disk synergy test.
AB  - We report on the first detection of an AmpC-type Ambler class C 1 (ACC-1) beta
      lactamase in Citrobacter freundi isolated from a patient also harboring ACC-1
      producing Escherichia coli and Klebsiella pneumoniae. We propose a simple
      cefoxitin-based double-disk synergy test (DDST) for the specific detection of ACC
      1 in members of the family Enterobacteriaceae, including natural AmpC producers,
      in association with a cloxacillin-based DDST as a first-line AmpC-type beta
      lactamase screening test.

PMID- 16971654
TI  - Immunosuppression and regulation: cast in new light?

PMID- 16971656
TI  - Renal effects of Coxsackie B4 virus in hyper-IgA mice.
AB  - For clarification of the pathogenetic role of viral infection in chronic
      glomerulonephritis, the renal effects of Coxsackie B4 virus (CB4) were examined
      in hyper-IgA (HIGA) mice. In experiment 1, HIGA mice (n = 75) were inoculated
      intravenously with live CB4 and inactivated CB4 once a month from 1 to 12 mo of
      age. In experiment 2, HIGA mice (n = 45) were inoculated intravenously with live
      CB4 and inactivated CB4 once at 6 wk of age. In experiment 3, 60 mice were
      inoculated intravenously with carbon and live or inactivated CB4 once at 6 wk of
      age. Mice in the control group were inoculated with vehicle. The kidneys were
      extirpated from five mice of each group killed with time after inoculation for
      histologic evaluation. The scores for mesangial IgA deposition, PCNA-positive
      cells, and matrix at 20 wk were higher in mice with live CB4 than in mice with
      inactivated CB4 or without CB4. On electron microscopic examination, swelling and
      detachment of endothelial cells from 24 h after inoculation and increase of serum
      IFN-gamma concentration were found in mice with live CB4. Many carbon particles
      were present in peripheral and central zones of the mesangium from 5 to 10 d in
      mice with carbon and live CB4. These results suggest that CB4 provokes
      exacerbation of renal pathologic findings in HIGA mice via endothelial injury,
      IFN-gamma production, and dysfunction of the mesangial pathway.

PMID- 16971655
TI  - Endothelial nitric oxide synthase deficiency produces accelerated nephropathy in
      diabetic mice.
AB  - Functionally significant polymorphisms in endothelial nitric oxide synthase
      (eNOS) and reduced vascular eNOS activity have been associated with increased
      human diabetic nephropathy (DN), but the pathogenic role of eNOS deficiency in
      the development of DN has not yet been confirmed. This study characterizes the
      severity of DN in eNOS(-/-) mice that were backcrossed to C57BLKS/J db/db mice.
      Although the severity of hyperglycemia was similar to C57BLKS/J db/db mice, by 26
      wk, eNOS(-/-) C57BLKS/J db/db mice exhibited dramatic albuminuria, arteriolar
      hyalinosis, increased glomerular basement membrane thickness, mesangial
      expansion, mesangiolysis, and focal segmental and early nodular
      glomerulosclerosis. Even more remarkable, eNOS(-/-) C57BLKS db/db exhibited
      decreases in GFR to levels <50% of that in eNOS(+/+) C57BLKS db/db, as confirmed
      by increased serum creatinine. In summary, eNOS(-/-) db/db mice provide the most
      robust model of type II DN that has been described to date and support a role for
      deficient eNOS-derived NO production in the pathogenesis of DN.

PMID- 16971658
TI  - Prevalence of mutations in renal developmental genes in children with renal
      hypodysplasia: results of the ESCAPE study.
AB  - Renal hypodysplasia (RHD) is characterized by a reduced nephron number, small
      kidney size, and disorganized renal tissue. A hereditary basis has been
      established for a subset of affected patients, suggesting a major role of
      developmental genes that are involved in early kidney organogenesis. Gene
      mutations that have dominant inheritance and cause RHD, urinary tract anomalies,
      and defined extrarenal symptoms have been identified in TCF2 (renal cysts and
      diabetes syndrome), PAX2 (renal-coloboma syndrome), EYA1 and SIX1 (branchio-oto
      renal syndrome), and SALL1 (Townes-Brocks syndrome). For estimation of the
      prevalence of these events, an unselected cohort of 99 unrelated patients with
      RHD that was associated with chronic renal insufficiency were screened for
      mutations in TCF2, PAX2, EYA1, SIX1, and SALL1. Mutations or variants in the
      genes of interest were detected in 17 (17%) unrelated families: One mutation, two
      variants, and four deletions of TCF2 in eight unrelated patients; four different
      PAX2 mutations in six families; one EYA1 mutation and one deletion in two
      patients with branchio-oto-renal syndrome; and one SALL1 mutation in a patient
      with isolated RHD. Of a total of 27 patients with renal cysts, six (22%) carried
      a mutation in TCF2. It is interesting that a SIX1 sequence variant was identified
      in two siblings with renal-coloboma syndrome as a result of a PAX2 mutation,
      suggesting an oligogenic inheritance. Careful clinical reevaluation that focused
      on discrete extrarenal symptoms and thorough family analysis revealed syndrome
      specific features in nine of the 17 patients. In conclusion, 15% of patients with
      RHD show mutations in TCF2 or PAX2, whereas abnormalities in EYA1, SALL1, and
      SIX1 are less frequent.

PMID- 16971657
TI  - Mitogen-activated protein kinases inhibit the ROMK (Kir 1.1)-like small
      conductance K channels in the cortical collecting duct.
AB  - It was demonstrated previously that low dietary potassium (K) intake stimulates
      Src family protein tyrosine kinase (PTK) expression via a superoxide-dependent
      signaling. This study explored the role of mitogen-activated protein kinase
      (MAPK) in mediating the effect of superoxide anions on PTK expression and ROMK
      (Kir 1.1) channel activity. Western blot analysis demonstrated that low K intake
      significantly increased the phosphorylation of P38 MAPK (P38) and extracellular
      signal-regulated kinase (ERK) but had no effect on phosphorylation of c-JUN N
      terminus kinase in renal cortex and outer medulla. The stimulatory effect of low
      K intake on P38 and ERK was abolished by treatment of rats with tempol. The
      possibility that increases in superoxide and related products that are induced by
      low K intake were responsible for stimulating phosphorylation of P38 and ERK also
      was supported by the finding that application of H(2)O(2) increased the
      phosphorylation of ERK and P38 in the cultured mouse collecting duct cells.
      Simultaneous blocking of ERK and P38 completely abolished the effect of H(2)O(2)
      on c-Src expression in mouse collecting duct cells. For determination of the role
      of P38 and ERK in the regulation of ROMK-like small-conductance K (SK) channels,
      the patch-clamp technique was used to study the effect of inhibiting P38 and ERK
      on SK channels in the cortical collecting duct from rats that were on a control K
      diet (1.1%) and on a K-deficient diet for 1 d. Inhibition of ERK, c-JUN N
      terminus kinase, or P38 alone had no effect on SK channels. In contrast,
      simultaneous inhibition of P38 and ERK significantly increased channel activity.
      The effect of inhibiting MAPK on SK channels was not affected in the presence of
      herbimycin A, a PTK inhibitor, and was larger in rats that were on a K-deficient
      diet than in rats that were on a normal-K diet. However, the stimulatory effect
      of inhibiting ERK and P38 on SK was absent in the cortical collecting duct that
      was treated with colchicine. It is concluded that low K intake-induced increases
      in superoxide levels are responsible for stimulation of P38 and ERK and that MAPK
      inhibit the SK channels by stimulating PTK expression and via a PTK-independent
      mechanism.

PMID- 16971659
TI  - A non-nephrotoxic gentamicin congener that retains antimicrobial efficacy.
AB  - Aminoglycoside antibiotics, although of major clinical importance in the
      treatment of serious Gram- negative infections and a potential therapeutic agent
      in the amelioration of diseases that are characterized by premature stop
      mutations, are associated with a high incidence of acute renal failure. With the
      use of HPLC techniques, the four components (congeners) of gentamicin, the most
      commonly used aminoglycoside, were isolated and characterized. Described here is
      a congener with minimal cytotoxicity in cell culture and animal studies that
      retained normal bactericidal properties in both Bacillus subtilis and a multidrug
      resistant form of Klebsiella pneumoniae. Furthermore, in animal studies, this
      congener failed to induce the functional and pathologic changes that are
      characteristic of gentamicin nephrotoxicity that is seen with the native
      compound. Finally, internalization of this non-nephrotoxic component was
      unaltered, but the subcellular distribution was different from native gentamicin
      or the other three cytotoxic congeners. These studies have identified a component
      of the native gentamicin congener mixture that retains its bactericidal
      properties with minimal or no apparent nephrotoxicity.

PMID- 16971660
TI  - High-dose chemotherapy for triple negative breast cancer.

PMID- 16971661
TI  - Time trends of breast cancer mortality in Spain during the period 1977-2001 and
      Bayesian approach for projections during 2002-2016.
AB  - BACKGROUND: In recent decades, changes in breast cancer (BC) mortality trends
      have been observed across Europe. Our objective is to describe BC mortality trend
      in Spain during 1977-2001 and to estimate BC mortality projection in the period
      2002-2016 using a Bayesian approach. MATERIAL AND METHODS: An age-period-cohort
      (APC) analysis has been carried out in order to investigate the effect of the
      age, period and birth cohort on BC mortality in Spain during 1977-2001 and to
      estimate future trends for the period 2002-2016. A Bayesian APC model with an
      autoregressive structure for the age parameters has been used for projections of
      BC mortality. RESULTS: BC mortality rates increased 2.18% per year during 1977
      1991 followed by a significant fall after 1992 (estimated annual percent change =
      -2.67%; 95% confidence interval = -2.97, -2.31). Cohorts born before 1952 showed
      higher risk of death from BC than those born after this year. Projections showed
      an increase of mortality among women older than 50 years in the period 2002-2016
      (range of increase = 10%-40%). CONCLUSIONS: The decrease of BC mortality since
      1992 could be attributable to BC down-staging due to early detection and
      effectiveness of cancer treatment. The effect of ageing on the female population,
      immigration and the increase of BC incidence observed in Spain could explain the
      increase in BC mortality predicted for the years to come among women older than
      50 years. BC screening to the whole Spanish population and new treatments
      introduced in the last few years could modify the predictions of BC mortality.
      Future forecasting studies should be carried out considering these new factors in
      the natural history of BC in Spain.

PMID- 16971662
TI  - Twice-daily pain monitoring as standard clinical practice for inpatients at a
      medical oncology unit: a descriptive study.
AB  - BACKGROUND: Very limited experiences have explored the use of pain intensity
      monitoring in everyday clinical practice at a medical oncology inpatient unit.
      METHODS: The program 'Pain-Free Hospital,' including a training course for nurses
      and the recording every 12 h of a visual analog scale (VAS) rating in all the
      patients admitted to the inpatients' ward independently of their disease stage,
      was activated in 2002. An audit on the clinical charts of patients admitted for
      the first time in the first semester of 2003 was carried out in order to
      ascertain the applicability of the procedure and its congruence with patients'
      clinical status. RESULTS: The VAS rating was reported in 211 out of 223 (94.6%)
      clinical charts. At entry, 60 out of 211 (28.4%) patients presented VAS>or=1, 21
      (35%) of whom were not taking any analgesics. The mean VAS score>or=1 was 3.4. No
      statistically significant difference emerged in the distribution of VAS rating as
      regards disease extension, presence or absence of bone metastases and performance
      status. CONCLUSIONS: The systematic monitoring of VAS by nurses at a medical
      oncology inpatients' ward is feasible with a good patient compliance. The
      reliability of the procedure in terms of guiding the analgesic treatment has yet
      to be demonstrated.

PMID- 16971663
TI  - Increased chondroitin sulphate proteoglycan expression (B5 immunoreactivity) in
      metastases of uveal melanoma.
AB  - BACKGROUND: Metastatic uveal melanoma has a poor prognosis and limited
      therapeutic options. Proteoglycans are involved in tumor cell invasion and
      metastatic behavior. The mAbB5 stains a chondroitin sulphate proteoglycan (CSPG)
      on cutaneous melanoma cells. Here, we compare the B5-staining of CSPG in
      primaries and metastases of uveal melanoma. MATERIAL AND METHODS:
      Immunohistopathological staining was performed in 15 cutaneous and 39 uveal
      melanoma samples. A score for intracellular and surface staining was established.
      B5 staining was compared in primaries and metastases of uveal melanoma using
      Student's t-test. RESULTS: Eight of 11 (73%) uveal melanoma metastases were
      positive for B5-staining whereas only 5 of 28 (18%) primary uveal melanoma
      samples were B5-positive (P < 0.001). Nine of 15 cutaneous melanoma samples (60%)
      were B5-positive without significant difference between primary and metastatic
      lesions. Surface staining was found both on uveal melanoma metastases and
      cutaneous melanomas. CONCLUSIONS: CSPG was expressed significantly more often in
      metastases than in primaries of uveal melanoma. It potentially may be one factor
      associated with metastatic spread. Further studies are needed to determine its
      use as prognostic factor. The mAbB5 may also be a promising tool for
      immunotherapy due to its strong staining of CSPG on the surface of cutaneous and
      metastatic uveal melanoma cells.

PMID- 16971664
TI  - A randomized phase II trial of gemcitabine plus treosulfan versus treosulfan
      alone in patients with metastatic uveal melanoma.
AB  - BACKGROUND: Several trials demonstrated efficacy of the gemcitabine/treosulfan
      (GeT) combination in metastatic uveal melamoma. This randomized phase II trial
      compared the GeT combination versus treosulfan alone (T) in this rare disease.
      PATIENTS AND METHODS: Chemotherapy-naive patients with proven metastatic uveal
      melanoma were randomly assigned to receive 1000 mg/m(2) of gemcitabine plus 3500
      mg/m(2) of treosulfan (GeT) or 3500 mg/m(2) of T. Chemotherapy was administered
      on days 1 and 8 in both arms, cycles were repeated on day 29. Primary end point
      was rate of responses and disease stabilizations. RESULTS: Forty-eight patients
      were randomized. Seven confirmed stable diseases (SDs) and one partial remission
      (PR) were observed in 24 patients treated with the GeT regimen, whereas no PR and
      only three SDs were observed in the T arm (P = 0.08). Median progression-free
      survival (PFS) was 3 months (95% CI 1.1-4.9) and 2 months (95% CI 1.7-2.3) in the
      GeT and T arm (P = 0.008, log-rank). Six and 12 months PFS was 34.8% and 17.9%
      and 16.7% and 0% always favoring the GeT arm. CONCLUSIONS: This first randomized
      trial in metastatic uveal melanoma showed a superior PFS and a trend for a higher
      response/stabilization rate of the GeT combination over T.

PMID- 16971665
TI  - A phase II study of bortezomib in mantle cell lymphoma: the National Cancer
      Institute of Canada Clinical Trials Group trial IND.150.
AB  - BACKGROUND: We evaluated the activity and toxic effects of bortezomib in patients
      with mantle cell lymphoma. PATIENTS AND METHODS: Thirty patients, including 29
      eligible patients, were enrolled; 13 had received no prior chemotherapy. The dose
      of bortezomib was 1.3 mg/m2 given on days 1, 4, 8 and 11 every 21 days. Response
      was assessed according to the International Workshop Criteria for non-Hodgkin's
      lymphoma and toxicity graded using the National Cancer Institute Common Toxicity
      Criteria version 2.0. RESULTS: There were 13 responding patients (46.4%; 95%
      confidence interval=27.5% to 66.1%), including one unconfirmed complete
      remission. The median response duration was 10 months. Response rates were
      similar in previously untreated (46.2%) and treated (46.7%) patients.
      Neurological toxicity and myalgia led to treatment discontinuation in 10 patients
      after two to seven treatment cycles. Five serious adverse events (including two
      deaths) associated with fluid retention were observed in the first 12 patients.
      We subsequently excluded patients with baseline effusions, dyspnea or edema; no
      further events were seen. CONCLUSIONS: Bortezomib is active in treating patients
      with mantle cell lymphoma. While cumulative neuromuscular toxic effects limited
      therapy duration and specific issues related to fluid retention require further
      evaluation, continued study of this drug in combination regimens is warranted.

PMID- 16971666
TI  - A prospective, blinded analysis of thymidylate synthase and p53 expression as
      prognostic markers in the adjuvant treatment of colorectal cancer.
AB  - BACKGROUND: Despite previous studies, uncertainty has persisted about the role of
      thymidylate synthase (TS) and p53 status as markers of prognosis in colorectal
      cancer (CRC). PATIENTS AND METHODS: A total of 967 patients accrued to a large
      adjuvant trial in CRC were included in a prospectively planned molecular
      substudy, and of them, 59% had rectal cancer and about 90% received adjuvant
      chemotherapy (either systemically or randomly allocated to intraportal 5
      fluorouracil infusion or both). TS and p53 status were determined, blinded to any
      clinical data, by immunohistochemistry using a validated polyclonal antibody or
      the DO-7 clone, respectively, and their relationships with overall survival were
      examined. RESULTS: High TS expression was observed in 58% and overexpression of
      p53 in 60% of tumours. TS expression correlated with tumour stage, and p53
      overexpression, with rectal cancers. There was no evidence that either marker was
      significantly associated with survival by either univariate (TS hazard ratio (HR)
      = 0.94, 95% CI 0.76-1.18 and P = 0.6 and p53 HR = 0.98, 95% CI 0.78-1.23 and P =
      0.9) or multivariate analyses (TS HR = 0.99, 95% CI 0.79-1.25 and P = 0.9 and p53
      HR = 0.98, 95% CI 0.78-1.23 and P = 0.8). CONCLUSIONS: Neither TS nor p53
      expression has significant prognostic value in the adjuvant setting of CRC.

PMID- 16971667
TI  - Pathology practice patterns affect lymph node evaluation and outcome of colon
      cancer: a population-based study.
AB  - BACKGROUND: A large variation in the number of nodes examined between patients,
      hospitals, and regions has been reported for patients with colon cancer. We
      studied determinants of this variation and its relation to survival in the south
      of The Netherlands. PATIENTS AND METHODS: All patients who underwent resection
      for stage I-III colon carcinoma diagnosed from 1999 to 2002 in the Eindhoven
      Cancer Registry area were included (n = 2168). Determinants of lymph node
      evaluation and their relationship to survival were assessed, including variation
      between the six departments of pathology. RESULTS: A median number of six lymph
      nodes per specimen had been examined. The median number for each department of
      pathology ranged from three to eight (P < 0.0001). After correction for relevant
      factors, this variation remained, resulting in differences in the proportion of
      N+ tumours between departments from 29% to 41% (P < 0.0001). The number of nodes
      examined was positively associated with survival. Survival for node-negative
      patients differed between the departments of pathology (up to hazard ratio 1.5; P
      = 0.02). CONCLUSION: There was a large variation in lymph node evaluation between
      the departments of pathology, leading to differences in stage distribution and
      survival. Intervention strategies should be directed at nodal assessment.

PMID- 16971668
TI  - Occupational exposure to diesel exhausts and risk for lung cancer in a population
      based case-control study in Italy.
AB  - BACKGROUND: We studied the effect of exposure to diesel exhausts on lung cancer
      risk in a population-based case-control study in the city of Turin, Italy.
      PATIENTS AND METHODS: Information on occupational histories of 595 incident lung
      cancer cases diagnosed in 1991-1992 and 845 population controls was obtained.
      During the interviews, diesel job-specific modules (D-JSMs) were administered
      whenever subjects had worked in occupations included in the following nine
      categories: railroad workers, miners, professional drivers and transport
      conductors, heavy-machine operators, mechanics and testers, filling station
      attendants, motor-vehicle park attendants, transport equipment operators, and
      occupations carried out in/near urban roads. All D-JSMs were evaluated for
      probability, intensity and frequency of exposure. RESULTS: The odds ratio for
      ever exposure to diesel exhausts was 1.04 (95% confidence interval 0.79-1.37),
      after adjusting for age, sex, smoking and having worked in occupations entailing
      exposure to known lung carcinogens. No association was found with intensity,
      probability and duration of exposure. CONCLUSIONS: Although misclassification of
      the exposure may have contributed to the negative results, we did not find an
      association between occupational exposure to diesel exhausts and lung cancer
      risk.

PMID- 16971669
TI  - Automated quantitative analysis of DCC tumor suppressor protein in ovarian cancer
      tissue microarray shows association with beta-catenin levels and outcome in
      patients with epithelial ovarian cancer.
AB  - BACKGROUND: The deleted in colorectal cancer (DCC) protein, the product of DCC
      tumor suppressor gene, is frequently altered in cancer. Preclinical data
      demonstrate that DCC regulates beta-catenin levels. Here, we sought to determine
      the association of DCC with beta-catenin protein levels, clinicopathological
      parameters and patient outcome in ovarian cancer using a method of in situ
      compartmentalized protein analysis. METHODS: A tissue array composed of 150
      advanced-stage ovarian cancers, treated with surgical debulking and platinum
      paclitaxel (Taxol) combination chemotherapy, was constructed. For evaluation of
      protein expression, we used an immunofluorescence-based method of automated in
      situ quantitative measurement of protein analysis (AQUA). RESULTS: One hundred
      and twelve patients (74%) had sufficient tissue for AQUA. The median follow-up
      time for the entire cohort was 33 months. Patients with low nuclear DCC
      expression had a 3-year progression-free survival (PFS) rate of 0% compared with
      33% of those with high DCC expression (P = 0.0067). In multivariate analysis, low
      nuclear DCC expression level retained its prognostic significance for PFS.
      Between DCC and beta-catenin, a significant relationship was found, where tumors
      with low DCC had low beta-catenin and vice versa (P = 0.003). CONCLUSIONS: Low
      nuclear DCC levels predict for poor patient outcome in epithelial ovarian cancer.
      DCC may exert its antitumor function, in part, through regulation of beta-catenin
      levels.

PMID- 16971670
TI  - Phase II trial of irinotecan plus oxaliplatin and 5-fluorouracil/leucovorin in
      patients with untreated metastatic gastric adenocarcinoma.
AB  - BACKGROUND: This nonrandomized open label phase II study evaluated the efficacy
      and safety of FOLFOXIRI in metastatic or recurrent gastric cancer patients.
      PATIENTS AND METHODS: Patients with histologically proven, metastatic gastric
      adenocarcinoma, aged 18-70 years, performance status zero to two, no prior
      chemotherapy, and with signed written informed consent were eligible. Treatment
      consisted of irinotecan 150 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin
      100 mg/m2 day 1, and 5-fluorouracil 2000 mg/m2 as a 48-h continuous infusion
      starting on day 1, which was repeated every 2 weeks. RESULTS: From August 2004 to
      August 2005, 48 patients were prospectively enrolled. The median age was 54 years
      (24-69). In total, 386 cycles were administered with a median of nine cycles per
      patient (range 1-12 cycles) and 45 of 48 patients were assessable for treatment
      response. An independent review of tumor responses resulted in overall response
      rate of 66.7% (95% confidence interval=53.4% to 80.0%) by intent-to-treat
      analysis with one complete response and 31 partial responses. The median survival
      of all patients was 14.8 months and the median time to progression was 9.6
      months. Most common grade 3/4 toxic effects were neutropenia (12% of all cycles)
      and emesis (8% of all cycles). Grade 2 peripheral neuropathy occurred in five
      patients. One (2%) patient had severe tumor bleeding and five (10%) patients
      experienced grade 3 diarrhea. CONCLUSIONS: The modified FOLFOXIRI combination
      chemotherapy showed a very promising preliminary antitumor activity and was
      generally well tolerated as a first-line treatment of patients with metastatic
      gastric cancer.

PMID- 16971671
TI  - Menopausal-type symptoms in young breast cancer survivors.
AB  - BACKGROUND: There has been little previous information available about menopausal
      type symptoms in very young breast cancer survivors. METHODS: In collaboration
      with the Young Survival Coalition, we conducted an Internet-based survey of women
      with a history of breast cancer diagnosed at age 40 years or younger using items
      derived from the Breast Cancer Prevention Trial symptom checklist. RESULTS: A
      total of 371 respondents were eligible for analysis. Mean age at diagnosis was
      32.8 years and mean age at follow-up 36.2 years; 89% of women received
      chemotherapy, 49% tamoxifen, 15% ovarian suppression, 4% aromatase inhibitors. At
      the time of survey, 37% were taking tamoxifen and 9% ovarian suppression.
      Excluding women on ovarian suppression, 77% of women were premenopausal at follow
      up. Many women reported bothersome menopausal-type symptoms. In particular, 46%
      of women reported hot flashes and 39% reported dyspareunia. In a linear
      regression model of symptom scores, current ovarian suppression, postmenopausal
      status, baseline anxiety before the diagnosis, pregnancy after the diagnosis,
      prior chemotherapy, and lower perceived financial status were associated with
      more bothersome symptoms. CONCLUSION: A substantial number of young breast cancer
      survivors experience bothersome menopausal symptoms. While the women who
      responded to our survey may represent a select group of survivors, these findings
      may have important implications for treatment decision making and long-term
      quality of life of young women with breast cancer.

PMID- 16971672
TI  - Understanding successful behaviour change: the role of intentions, attitudes to
      the target and motivations and the example of diet.
AB  - Although many attempts to change health behaviour fail, some individuals do show
      successful behaviour change. This study assessed the role of behavioural
      intentions, motivations and attitudes to the target in explaining successful
      changes in diet with a particular focus on positive and negative intentions and
      positive and negative attitudes. Participants (n=282) completed a questionnaire
      describing a recent change in eating behaviour (becoming a vegetarian, cutting
      out a food group, eating fewer calories), their intentions, their attitudes to
      the food being avoided, a range of motivations and their degree of success. The
      results showed that the three behaviour change groups differed in terms of their
      cognitions with those trying to eat fewer calories reporting less success in
      changing their behaviour. Successful vegetarianism was associated with a lower
      positive attitude; successfully cutting out a food group was related to ethical
      motivations, a lower positive attitude and greater positive and negative
      intentions, and reducing calorie intake was associated with greater positive
      intentions and a lower positive attitude. Therefore, success was associated with
      different cognitions depending upon the type of change being made, although
      cognitions such as 'I will eat more vegetables' and 'I no longer find high fat
      foods palatable' were consistently most predictive of success. Suggestions for
      the development of more effective interventions to change health behaviours are
      made.

PMID- 16971673
TI  - Twelve-month effects of Canada on the Move: a population-wide campaign to promote
      pedometer use and walking.
AB  - Canada on the Move is a national campaign to promote pedometer use and walking
      among adult Canadians. The purpose of this paper is to investigate the
      initiative's impact on sufficient walking, defined here as at least an hour daily
      in the week prior to the survey. Data were collected via the national Canadian
      Physical Activity Monitor's rolling monthly sample throughout 2004. Population
      prevalence rates of walking were compared using Bonferroni-adjusted confidence
      intervals. Correlates of sufficient walking were estimated using odds ratios
      adjusted for age, sex, income and education. Message recall and pedometer
      ownership were associated with increased odds of self-reported walking. There was
      evidence of a campaign effect on walking behavior independent of secular trends.
      The increased likelihood of sufficient walking suggests an ongoing role for
      nationally funded public awareness campaigns. The effectiveness of health
      promotion to increase walking may be enhanced by combining motivational health
      related messages with the dissemination and adoption of an easy-to-use tool for
      self-monitoring purposes.

PMID- 16971674
TI  - Effectiveness of an online computer-tailored physical activity intervention in a
      real-life setting.
AB  - The aim of this study was to evaluate the effectiveness of a computer-tailored
      physical activity intervention delivered through the Internet in a real-life
      setting. Healthy adults (n=526), recruited in six worksites, between 25 and 55
      years of age were randomized to one of three conditions receiving, respectively,
      (i) online-tailored physical activity advice + stage-based reinforcement e-mails,
      (ii) online-tailored physical activity advice only, (iii) online non-tailored
      standard physical activity advice. At 6-month follow-up, no differences in
      physical activity between study conditions were found; total physical activity,
      physical activity at moderate intensity and physical activity in leisure time
      significantly increased in all study conditions between baseline and follow-up.
      Further evaluation of the intervention materials showed that the tailored advice
      was more read, printed and discussed with others than the standard advice. Most
      of the respondents in the e-mail group indicated to be satisfied about the
      number, frequency and usefulness of the stage-based e-mails. In conclusion,
      although tailored advice was appreciated more than standard advice, no evidence
      was found that an online-tailored physical activity intervention program
      outperformed online standard information.

PMID- 16971675
TI  - Neurosteroids involved in regulating inhibition in the inferior colliculus.
AB  - Fast inhibitory neurotransmission in the brain is largely mediated by the gamma
      aminobutyric acid-type A (GABA(A)) receptor. The 3alpha,5alpha-reduced
      neurosteroids (e.g., allopregnanolone) are the most potent endogenous modulators
      of the GABA(A) receptor. Although it is known that 3alpha,5alpha-reduced
      neurosteroid levels change during stress or depression and over the estrus cycle,
      a basic physiological role consistent with their pharmacological action remains
      elusive. We used the unique architecture of the auditory midbrain to reveal a
      role for 3alpha,5alpha-reduced neurosteroids in regulating inhibitory efficacy.
      After blocking the massive GABAergic projection from the dorsal nucleus of the
      lateral lemniscus (DNLL) to the contralateral central nucleus of the inferior
      colliculus (ICC) in anesthetized rats, a reactive increase in the efficacy of
      other inhibitory circuits in the ICC (separable because of the dominant ear that
      drives each circuit) was demonstrated with physiological measures-single-neuron
      activity and a neural-population-evoked response. This effect was prevented by
      blocking 3alpha,5alpha-reduced neurosteroid synthesis with a 5alpha-reductase
      inhibitor: finasteride. Immunohistochemistry confirmed that the DNLL blockade
      induced an increase in 3alpha,5alpha-reduced neurosteroids in the contralateral
      ICC. This study shows that when GABAergic inhibition is reduced, the brain
      compensates within minutes by locally increasing synthesis of neurosteroids,
      thereby balancing excitatory and inhibitory inputs in complex neural circuits.

PMID- 16971676
TI  - Nucleus-specific abnormalities of GABAergic synaptic transmission in a genetic
      model of absence seizures.
AB  - Human and experimental studies indicate that molecular genetic changes in GABA(A)
      receptors may underlie the expression of spike-and-waves discharges (SWDs)
      occurring during absence seizures. However, the full spectrum of the genetic
      defects underlying these seizures has only been partially elucidated, the
      expression and functional profiles of putative abnormal protein(s) within the
      thalamocortical network are undefined, and the pathophysiological mechanism(s) by
      which these proteins would lead to absence paroxysms are poorly understood. Here
      we investigated GABA(A) inhibitory postsynaptic currents (IPSCs) in key
      thalamocortical areas, i.e., the somatosensory cortex, ventrobasal thalamus (VB)
      and nucleus reticularis thalami (NRT), in preseizure genetic absence epilepsy
      rats from Strasbourg (GAERS), a well-established genetic model of typical absence
      seizures that shows no additional neurological abnormalities, and compared their
      properties to age-matched non-epileptic controls (NECs). Miniature GABA(A) IPSCs
      of VB and cortical layers II/III neurons were similar in GAERS and NEC, whereas
      in GAERS NRT neurons they had 25% larger amplitude, 40% faster decay. In
      addition, baclofen was significantly less effective in decreasing the frequency
      of NRT mIPSCs in GAERS than in NEC, whereas no difference was observed for
      cortical and VB mIPSCS between the two strains. Paired-pulse depression was 45%
      smaller in GAERS NRT, but not in VB, and was insensitive to GABA(B) antagonists.
      These results point to subtle, nucleus-specific, GABA(A) receptor abnormalities
      underlying SWDs of typical absence seizures rather than a full block of these
      receptors across the whole thalamocortical network, and their occurrence prior to
      seizure onset suggests that they might be of epileptogenic significance.

PMID- 16971677
TI  - Neural correlates of sustained spatial attention in human early visual cortex.
AB  - Attention is thought to enhance perceptual performance at attended locations
      through top-down attention signals that modulate activity in visual cortex. Here,
      we show that activity in early visual cortex is sustained during maintenance of
      attention in the absence of visual stimulation. We used functional magnetic
      resonance imaging (fMRI) to measure activity in visual cortex while human
      subjects performed a visual detection task in which a variable-duration delay
      period preceded target presentation. Portions of cortical areas V1, V2, and V3
      representing the attended part of the visual field exhibited sustained increases
      in activity throughout the delay period. Portions of these cortical areas
      representing peripheral, unattended parts of the visual field displayed sustained
      decreases in activity. The data were well fit by a model that assumed the
      sustained neural activity was constant in amplitude over a time period equal to
      that of the actual delay period for each trial. These results demonstrate that
      sustained attention responses are present in early visual cortex (including
      primary visual cortex), in the absence of a visual stimulus, and that these
      responses correlate with the allocation of visuospatial attention in both the
      spatial and temporal domains.

PMID- 16971678
TI  - Multisensory orientation behavior is disrupted by neonatal cortical ablation.
AB  - The integration of visual and auditory information can significantly amplify the
      sensory responses of superior colliculus (SC) neurons and the behaviors that
      depend on them. This response amplification depends on the development of SC
      inputs that are derived from two regions of cortex: the anterior ectosylvian
      sulcus (AES) and the rostral lateral suprasylvian sulcus (rLS). Neonatal ablation
      of these cortico-collicular areas has been shown to disrupt the development of
      the multisensory enhancement capabilities of SC neurons and the present results
      demonstrate that it also precludes the development of the normal multisensory
      enhancements in orientation behavior. Animals with neonatal ablation of AES and
      rLS were tested at maturity and found unable to benefit from the combination of
      visual and auditory cues in their efforts to localize targets in contralesional
      space. In contrast, their ipsilesional multisensory orientation capabilities were
      indistinguishable from those of normal animals. However, when only one of these
      cortical areas was removed during early life, later behavioral consequences were
      negligible. Whether similar compensatory processes would occur in adult animals
      remains to be determined. These observations, coupled with those from previous
      studies, also suggest that a surprisingly high proportion of SC neurons capable
      of multisensory integration must be present for orientation behavior benefits to
      be realized. Compensatory mechanisms can achieve this if early lesions spare
      either AES or rLS, but even the impressive plasticity of the neonatal brain
      cannot compensate for the early loss of both of them.

PMID- 16971680
TI  - Large-scale organization of preferred directions in the motor cortex. II.
      Analysis of local distributions.
AB  - The spatial arrangement of preferred directions (PDs) in the primary motor cortex
      has revealed evidence for columnar organization and short-range order. We
      investigated the large-scale properties of this arrangement. We recorded neural
      activity at sites on a grid covering a large region of the arm area of the motor
      cortex while monkeys performed a 3D reaching task. Sites were projected to the
      cortical surface along anatomically defined cortical columns and a PD was
      extracted from each site with directionally tuned activity. We analyzed the
      resulting 2D surface map of PDs. Consistent with previous studies, we found that
      any particular reaching direction was re-represented at many points across the
      recorded area. In particular, we determined that the median radius of a cortical
      region required to represent the full complement of reaching directions is at
      most 1 mm. We also found that for the majority of regions of this size, the
      distribution of PDs within them exhibits an enrichment for the representation of
      forward and backward reaching directions (see companion paper). Finally, we found
      that the error of a population vector estimate of reaching direction constructed
      from neural activity within these regions is small on average, but varies
      significantly across different sections of the motor cortex, with the highest
      levels of error sustained near the fundus of the central sulcus and lowest levels
      achieved near the crown. We interpret these findings in the context of two well
      known features of motor cortex, that is, its highly distributed anatomical
      organization and its behaviorally dependent plasticity.

PMID- 16971681
TI  - Large-scale organization of preferred directions in the motor cortex. I. Motor
      cortical hyperacuity for forward reaching.
AB  - We used statistical methods for spherical density estimation to evaluate the
      distribution of preferred directions of motor cortical cells recorded from
      monkeys making reaching movements in 3D space. We found that this distribution,
      although broad enough to represent the entire 3D continuum of reaching
      directions, exhibited an enrichment for reaching forward from the body and, to a
      lesser degree, for reaching backward toward the body. The distribution of
      preferred directions of cells in the motor cortex may have important implications
      for motor cortical function and for the decoding of arm trajectories from
      population activity.

PMID- 16971679
TI  - Neurophysiology of prehension. I. Posterior parietal cortex and object-oriented
      hand behaviors.
AB  - Hand manipulation neurons in areas 5 and 7b/anterior intraparietal area (AIP) of
      posterior parietal cortex were analyzed in three macaque monkeys during a trained
      prehension task. Digital video recordings of hand kinematics synchronized to
      neuronal spike trains were used to correlate firing rates of 128 neurons with
      hand actions as the animals grasped and lifted rectangular and round objects. We
      distinguished seven task stages: approach, contact, grasp, lift, hold, lower, and
      relax. Posterior parietal cortex (PPC) firing rates were highest during object
      acquisition; 88% of task-related area 5 neurons and 77% in AIP/7b fired maximally
      during stages 1, 2, or 3. Firing rates rose 200-500 ms before contact, peaked at
      contact, and declined after grasp was secured. 83% of area 5 neurons and 72% in
      AIP/7b showed significant increases in mean rates during approach as the fingers
      were preshaped for grasp. Somatosensory signals at contact provided feedback
      concerning the accuracy of reach and helped guide the hand to grasp sites. In
      error trials, tactile information was used to abort grasp, or to initiate
      corrective actions to achieve task goals. Firing rates declined as lift began.
      41% of area 5 neurons and 38% in AIP/7b were inhibited during holding, and
      returned to baseline when grasp was relaxed. Anatomical connections suggest that
      area 5 provides somesthetic information to circuits linking AIP/7b to frontal
      motor areas involved in grasping. Area 5 may also participate in sensorimotor
      transformations coordinating reach and grasp behaviors and provide on-line
      feedback needed for goal-directed hand movements.

PMID- 16971682
TI  - Properties of a population of GABAergic cells in murine auditory cortex weakly
      excited by thalamic stimulation.
AB  - Feedforward inhibition triggered by thalamocortical (TC) afferents sharpens onset
      responses and shapes receptive fields of pyramidal cells in auditory cortex
      (ACx). Previous studies focused only on interneurons located in and around layer
      IV in primary ACx, target of the dense thalamic projections from ventral medial
      geniculate. We investigated a population of feedforward interneurons located
      throughout layers I-V and activated by both afferents from primary and nonprimary
      thalamus using recordings from auditory TC brain slices obtained from mice
      expressing green fluorescent protein under control of the glutamic acid
      decarboxylase (GAD65) promoter in a subpopulation of cortical GABAergic cells. We
      studied the responses of these interneurons and of pyramidal cells in ACx to
      thalamic stimulation and to hyper- and depolarizing current pulses. Most
      interneurons exhibited monosynaptic responses to thalamic stimulation, but this
      excitation was weak and subthreshold. Interneurons had multipolar dendritic
      morphology with widespread and dense axonal projections extending several hundred
      micrometers from the soma. In pyramidal cells from layers II-IV, thalamic
      excitatory postsynaptic potentials were significantly larger than in interneurons
      and were superthreshold in 40% of cells, but in these cells, there was no
      evidence of feedforward inhibition. By contrast, feedforward inhibition was
      observed in 12 of 18 layer V pyramidal cells. Thus feedforward inhibition in
      supragranular layers of ACx is weak, and these interneurons require coincident
      excitation to be activated by thalamic inputs.

PMID- 16971683
TI  - Calcium-activated afterhyperpolarizations regulate synchronization and timing of
      epileptiform bursts in hippocampal CA3 pyramidal neurons.
AB  - Calcium-activated potassium conductances regulate neuronal excitability, but
      their role in epileptogenesis remains elusive. We investigated in rat CA3
      pyramidal neurons the contribution of the Ca(2+)-activated K(+)-mediated
      afterhyperpolarizations (AHPs) in the genesis and regulation of epileptiform
      activity induced in vitro by 4-aminopyridine (4-AP) in Mg(2+)-free Ringer.
      Recurring spike bursts terminated by prolonged AHPs were generated. Burst
      synchronization between CA3 pyramidal neurons in paired recordings typified this
      interictal-like activity. A downregulation of the medium afterhyperpolarization
      (mAHP) paralleled the emergence of the interictal-like activity. When the mAHP
      was reduced or enhanced by apamin and EBIO bursts induced by 4-AP were increased
      or blocked, respectively. Inhibition of the slow afterhyperpolarization (sAHP)
      with carbachol, t-ACPD, or isoproterenol increased bursting frequency and
      disrupted burst regularity and synchronization between pyramidal neuron pairs. In
      contrast, enhancing the sAHP by intracellular dialysis with KMeSO(4) reduced
      burst frequency. Block of GABA(A-B) inhibitions did not modify the abnormal
      activity. We describe novel cellular mechanisms where 1) the inhibition of the
      mAHP plays an essential role in the genesis and regulation of the bursting
      activity by reducing negative feedback, 2) the sAHP sets the interburst interval
      by decreasing excitability, and 3) bursting was synchronized by excitatory
      synaptic interactions that increased in advance and during bursts and decreased
      throughout the subsequent sAHP. These cellular mechanisms are active in the CA3
      region, where epileptiform activity is initiated, and cooperatively regulate the
      timing of the synchronized rhythmic interictal-like network activity.

PMID- 16971684
TI  - Modeling gravity-dependent plasticity of the angular vestibuloocular reflex with
      a physiologically based neural network.
AB  - A neural network model was developed to explain the gravity-dependent properties
      of gain adaptation of the angular vestibuloocular reflex (aVOR). Gain changes are
      maximal at the head orientation where the gain is adapted and decrease as the
      head is tilted away from that position and can be described by the sum of gravity
      independent and gravity-dependent components. The adaptation process was modeled
      by modifying the weights and bias values of a three-dimensional physiologically
      based neural network of canal-otolith-convergent neurons that drive the aVOR.
      Model parameters were trained using experimental vertical aVOR gain values. The
      learning rule aimed to reduce the error between eye velocities obtained from
      experimental gain values and model output in the position of adaptation. Although
      the model was trained only at specific head positions, the model predicted the
      experimental data at all head positions in three dimensions. Altering the
      relative learning rates of the weights and bias improved the model-data fits.
      Model predictions in three dimensions compared favorably with those of a double
      sinusoid function, which is a fit that minimized the mean square error at every
      head position and served as the standard by which we compared the model
      predictions. The model supports the hypothesis that gravity-dependent adaptation
      of the aVOR is realized in three dimensions by a direct otolith input to canal
      otolith neurons, whose canal sensitivities are adapted by the visual-vestibular
      mismatch. The adaptation is tuned by how the weights from otolith input to the
      canal-otolith-convergent neurons are adapted for a given head orientation.

PMID- 16971685
TI  - Forelimb movements and muscle responses evoked by microstimulation of cervical
      spinal cord in sedated monkeys.
AB  - Documenting the forelimb responses evoked by stimulating sites in primate
      cervical spinal cord is significant for understanding spinal circuitry and for
      potential neuroprosthetic applications involving hand and arm. We examined the
      forelimb movements and electromyographic (EMG) muscle responses evoked by
      intraspinal microstimulation in three M. nemestrina monkeys sedated with
      ketamine. Trains of three stimulus pulses (10-80 muA) at 300 Hz were delivered at
      sites in regularly spaced tracks from C6 to T1. Hand and/or arm movements were
      evoked at 76% of the 745 sites stimulated. Specifically, movements were evoked in
      digits (76% of effective sites), wrist (15% of sites), elbow (26%), and shoulder
      (17%). To document the muscle activity evoked by a stimulus current just capable
      of eliciting consistent joint rotation, stimulus-triggered averages of rectified
      EMG were calculated at each site where a movement was observed. Typically, many
      muscles were coactivated at threshold currents needed to evoke movements. Out of
      the 13-15 muscles recorded per animal, only one muscle was active at 14% of the
      effective sites and two to six muscles were coactivated at 47% of sites. Thus
      intraspinal stimulation at threshold currents adequate for evoking movement
      typically coactivated multiple muscles, including antagonists. Histologic
      reconstruction of stimulation sites indicated that responses were elicited from
      the dorsal and ventral horn and from fiber tracts in the white matter, with
      little somatotopic organization for movement or muscle activation. The absence of
      a clear somatotopic map of output sites is probably a result of the stimulation
      of complex mixtures of fibers and cells.

PMID- 16971686
TI  - Taste responsiveness of fungiform taste cells with action potentials.
AB  - It is known that a subset of taste cells generate action potentials in response
      to taste stimuli. However, responsiveness of these cells to particular tastants
      remains unknown. In the present study, by using a newly developed extracellular
      recording technique, we recorded action potentials from the basolateral membrane
      of single receptor cells in response to taste stimuli applied apically to taste
      buds isolated from mouse fungiform papillae. By this method, we examined taste
      cell responses to stimuli representing the four basic taste qualities (NaCl, Na
      saccharin, HCl, and quinine-HCl). Of 72 cells responding to taste stimuli, 48
      (67%) responded to one, 22 (30%) to two, and 2 (3%) to three of four taste
      stimuli. The entropy value presenting the breadth of responsiveness was 0.158 +/-
      0.234 (mean +/- SD), which was close to that for the nerve fibers (0.183 +/-
      0.262). In addition, the proportion of taste cells predominantly sensitive to
      each of the four taste stimuli, and the grouping of taste cells based on
      hierarchical cluster analysis, were comparable with those of chorda tympani (CT)
      fibers. The occurrence of each class of taste cells with different taste
      responsiveness to the four taste stimuli was not significantly different from
      that of CT fibers except for classes with broad taste responsiveness. These
      results suggest that information derived from taste cells generating action
      potentials may provide the major component of taste information that is
      transmitted to gustatory nerve fibers.

PMID- 16971687
TI  - Residual bound Ca2+ can account for the effects of Ca2+ buffers on synaptic
      facilitation.
AB  - Facilitation is a transient stimulation-induced increase in synaptic response, a
      ubiquitous form of short-term synaptic plasticity that can regulate synaptic
      transmission on fast time scales. In their pioneering work, Katz and Miledi and
      Rahamimoff demonstrated the dependence of facilitation on presynaptic Ca(2+)
      influx and proposed that facilitation results from the accumulation of residual
      Ca(2+) bound to vesicle release triggers. However, this bound Ca(2+) hypothesis
      appears to contradict the evidence that facilitation is reduced by exogenous
      Ca(2+) buffers. This conclusion led to a widely held view that facilitation must
      depend solely on the accumulation of Ca(2+) in free form. Here we consider a more
      realistic implementation of the bound Ca(2+) mechanism, taking into account
      spatial diffusion of Ca(2+), and show that a model with slow Ca(2+) unbinding
      steps can retain sensitivity to free residual Ca(2+). We demonstrate that this
      model agrees with the facilitation accumulation time course and its biphasic
      decay exhibited by the crayfish inhibitor neuromuscular junction (NMJ) and relies
      on fewer assumptions than the most recent variants of the free residual Ca(2+)
      hypothesis. Further, we show that the bound Ca(2+) accumulation is consistent
      with Kamiya and Zucker's experimental results, which revealed that photolytic
      liberation of a fast Ca(2+) buffer decreases the synaptic response within
      milliseconds. We conclude that Ca(2+) binding processes with slow unbinding times
      (tens to hundreds of milliseconds) constitute a viable mechanism of synaptic
      facilitation at some synapses and discuss the experimental evidence for such a
      mechanism.

PMID- 16971688
TI  - Paying attention. Focus on "State-dependent modulation of time-varying gustatory
      responses".

PMID- 16971689
TI  - PKC modulation of transmitter release by SNAP-25 at sensory-to-motor synapses in
      aplysia.
AB  - Activation of phosphokinase C (PKC) can increase transmitter release at sensory
      motor neuron synapses in Aplysia, but the target of PKC phosphorylation has not
      been determined. One putative target of PKC at synapses is the synaptosomal
      associated protein of 25 kDa (SNAP-25), a member of the SNARE protein complex
      implicated in synaptic vesicle docking and fusion. To determine whether PKC
      regulated transmitter release through phosphorylation of SNAP-25, we cloned
      Aplysia SNAP-25 and expressed enhanced green fluorescent protein (EGFP)-coupled
      SNAP-25 constructs mutated at the PKC phosphorylation site Ser198 in Aplysia
      sensory neurons. We found several distinct effects of expression of EGFP-SNAP-25
      constructs. First, the rates of synaptic depression were slowed when cells
      contained SNAP-25 with phosphomimetic residues Glu or Asp. Second, PDBu-mediated
      increases in transmitter release at naive synapses were blocked in cells
      expressing nonphosphorylated-state SNAP-25. Finally, expression of EGFP-coupled
      SNAP-25 but not uncoupled SNAP-25 inhibited 5-HT-mediated reversal of depression
      and the ability of EGFP-coupled SNAP-25 to inhibit the reversal of depression was
      affected by changes at Ser198. These results suggest SNAP-25 and phosphorylation
      of SNAP-25 by PKC can regulate transmitter release at Aplysia sensory-motor
      neuron synapses by a number of distinct processes.

PMID- 16971690
TI  - The craniofacial characteristics of osteogenesis imperfecta patients.
AB  - The aim of this study was to identify the craniofacial characteristics of 16
      osteogenesis imperfecta (OI) patients, 10 males and 6 females, aged 7-15 years.
      The control group comprised 863 Chinese children from 6 to 18 years of age.
      Eleven cephalometric reference points and 25 variables were measured on the
      lateral cephalometric radiographs. Cochrane's method of unequal variance t-test
      was used to differentiate the differences between two groups. A Class III
      occlusal relationship was found in 62.5 per cent of the OI patients. The maxilla
      was more retrusive than the mandible in relation to the cranial base. Face
      heights, the effective maxilla and mandibular lengths, and anterior and posterior
      cranial base lengths were significantly shorter than the control subjects. The
      facial divergence, the cranial base (N-S-Ar, P<0.001), and the gonial (Ar-Go-Gn,
      P<0.001) angles were significantly enlarged, while the articular angle (S-Ar-Go,
      P<0.001) was significantly reduced. The findings showed that the OI patient had a
      more prominent Class III occlusal relationship, prognathic mandible, larger
      facial divergence, shorter face heights, defective sagittal growth of the maxilla
      and mandible, a flattened cranial base angle, impaired cranial base growth, and
      more forward counterclockwise rotation in mandibular growth compared with the
      controls.

PMID- 16971691
TI  - An interactive taxonomy of MR imaging sequences.
AB  - Discerning an underlying structure in the array of magnetic resonance (MR)
      imaging sequences and acronyms available is a bewildering task. Attempts have
      been made to present standard taxonomies of MR imaging sequences, primarily on
      the basis of their underlying physics. Despite this, it is difficult to usefully
      incorporate given taxonomies into routine clinical knowledge. The links,
      differences, and similarities among sequences are multidimensional and too
      complex for tabular presentation on the printed page. The authors present an
      interactive taxonomy of MR imaging sequences. With this graphical interface, the
      user can explore the changing relationships among a wide range of sequence types
      as they are viewed from different perspectives and through different
      associations, working through a natural learning process.

PMID- 16971692
TI  - Evidence for transit peptide acquisition through duplication and subsequent
      frameshift mutation of a preexisting protein gene in rice.
AB  - Many proteins synthesized in the cytosol are delivered to their appropriate
      compartments in the cell by specific targeting signals. Here, we provide new
      insight into the generation of the chloroplast-targeting signal (called the
      transit peptide) in rice. First, we identified the mitochondrial ribosomal
      protein L13 (mt rpl13) gene on chromosome 5. Downstream of the gene, we
      identified a DNA fragment of 266 bp: a segment within a duplication of mt rpl13.
      The duplicated region was transcribed and found to encode an open reading frame
      (ORF) of 160 amino acids (aa) (orf160). The orf160 gene comprises C-terminal 60
      aa derived from the mt rpl13 gene and N-terminal 100 aa derived from another
      duplicated fragment of a pentatricopeptide repeat (ppr)564 gene that encodes 564
      aa with ppr motifs on chromosome 1. Examination of the localization of the ORF160
      protein tagged with green fluorescent protein (GFP) showed that it is targeted to
      the chloroplasts. As such, ORF160 clearly contains a transit peptide.
      Interestingly, this was translated from the alternative reading frame of the
      duplicated fragment of ppr564. To confirm this, the reading frame of the ppr564
      gene was shifted according to that of the orf160 gene, and the frameshifted
      ppr564 sequence was fused to the gene for GFP. The expressed GFP-fused protein
      was also located in the chloroplasts. These results provide clear evidence for
      the generation of the transit peptide through duplication and subsequent
      frameshifting of a reading frame of a preexisting protein gene. We also
      demonstrate the importance of sequence redundancy and frameshift mutation in this
      evolutionary process.

PMID- 16971693
TI  - Nucleus-to-nucleus gene transfer and protein retargeting into a remnant cytoplasm
      of cryptophytes and diatoms.
AB  - The complex plastid of the cryptophyte Guillardia theta and of the diatom
      Phaeodactylum tricornutum can both be traced back to an engulfed eukaryotic red
      alga. The eukaryotic origin of these plastids is most obvious in cryptophytes,
      where the organelle still possesses a remnant nucleus, the nucleomorph. The
      nucleomorph itself is embedded in the periplastid compartment (PPC), the remnant
      of the former red algal cytosol. In the cryptophyte and diatom, the complex
      plastid is surrounded by 4 membranes, the outer one being continuous with the
      host rough endoplasmatic reticulum. In a recent report, we have shown that a
      nuclear encoded PPC protein of G. theta expressed in P. tricornutum leads to a
      localization, recently described as being a "bloblike structure," which can be
      obtained by mutation of plastid protein-targeting sequences of the diatom itself.
      Here we present further nucleus-encoded PPC proteins from G. theta, such as the
      eukaryotic translation elongation factor-1alpha, evidence for their nucleus-to
      nucleus gene transfer, and retargeting of the proteins. We also investigated the
      first nuclear encoded PPC-targeted protein of P. tricornutum (Hsp70) and analyzed
      it for in vivo localization together with the identified G. theta PPC proteins.
      This revealed that all localize to the bloblike structures, which we suggest is
      the highly reduced PPC of P. tricornutum. Furthermore, the described cryptophyte
      PPC proteins possibly allow the elucidation of the processes by which proteins
      are involved in different levels of host control over its eukaryotic organelle.

PMID- 16971694
TI  - The influence of phylogenetic uncertainty on the detection of positive Darwinian
      selection.
AB  - The power of maximum likelihood tests of positive selection on protein-coding
      genes depends heavily on detecting and accounting for potential biases in the
      studied data set. Although the influence of transition:transversion and codon
      biases have been investigated in detail, little is known about how inaccuracy in
      the phylogeny used during the calculations affects the performance of these
      tests. In this study, 3 empirical data sets are analyzed using sets of simulated
      topologies corresponding to low, intermediate, and high levels of phylogenetic
      uncertainty. The detection of positive selection was largely unaffected by errors
      in the underlying phylogeny. However, the number of sites identified as being
      under positive selection tended to be overestimated.

PMID- 16971695
TI  - Global phylogeny determined by the combination of protein domains in proteomes.
AB  - The majority of proteins consist of multiple domains that are either repeated or
      combined in defined order. In this study, we survey the combination of protein
      domains defined at fold and fold superfamily levels in 185 genomes belonging to
      organisms that have been fully sequenced and introduce a method that reconstructs
      rooted phylogenomic trees from the content and arrangement of domains in proteins
      at a genomic level. We find that the majority of domain combinations were unique
      to Archaea, Bacteria, or Eukarya, suggesting most combinations originated after
      life had diversified. Domain repeat and domain repeat within multidomain proteins
      increased notably in eukaryotes, mainly at the expense of single-domain and
      domain-pair proteins. This increase was mostly confined to Metazoa. We also find
      an unbalanced sharing of domain combinations which suggests that Eukarya is more
      closely related to Bacteria than to Archaea, an observation that challenges the
      widely assumed eukaryote-archaebacterial sisterhood relationship. The occurrence
      and abundance of the molecular repertoire (interactome) of domain combinations
      was used to generate phylogenomic trees. These global interactome-based
      phylogenies described organismal histories satisfactorily, revealing the
      tripartite nature of life, and supporting controversial evolutionary patterns,
      such as the Coelomata hypothesis, the grouping of plants and animals, and the
      Gram-positive origin of bacteria. Results suggest strongly that the process of
      domain combination is not random but curved by evolution, rejecting the null
      hypothesis of domain modules combining in the absence of natural selection or an
      optimality criterion.

PMID- 16971696
TI  - Allogeneic stem cell transplantation corrects biochemical derangements in MNGIE.
AB  - Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a multisystemic
      autosomal recessive disease due to primary thymidine phosphorylase (TP)
      deficiency. To restore TP activity, we performed reduced intensity allogeneic
      stem cell transplantations (alloSCTs) in two patients. In the first, alloSCT
      failed to engraft, but the second achieved mixed donor chimerism, which partially
      restored buffy coat TP activity and lowered plasma nucleosides. Thus, alloSCT can
      correct biochemical abnormalities in the blood of patients with MNGIE, but
      clinical efficacy remains unproven.

PMID- 16971697
TI  - Voxel-based analysis of PET amyloid ligand [11C]PIB uptake in Alzheimer disease.
AB  - BACKGROUND: PET studies with N-methyl-[(11)C]2-(4':-methylaminophenyl)-6
      hydroxybenzothiazole ([(11)C]PIB) have revealed an increased tracer uptake in
      several brain regions in Alzheimer disease (AD). OBJECTIVE: To employ voxel-based
      analysis method to identify brain regions with significant increases in
      [(11)C]PIB uptake in AD vs healthy control subjects, indicative of increased
      amyloid accumulation in these regions. METHODS: We studied 17 patients with AD
      and 11 control subjects with PET using [(11)C]PIB as tracer. Parametric images
      were computed by calculating a region-to-cerebellum ratio over 60 to 90 minutes
      in each voxel. Group differences in [(11)C]PIB uptake were analyzed with
      statistical parametric mapping (SPM) and automated region-of-interest (ROI)
      analysis. RESULTS: SPM showed increased uptake (p < 0.001) in the frontal,
      parietal, and lateral temporal cortices as well as in the posterior cingulate and
      the striatum. No significant differences in uptake were found in the primary
      sensory and motor cortices, primary visual cortex, thalamus, and medial temporal
      lobe. These results were supported by automated ROI analysis, with most prominent
      increases in AD subjects in the frontal cortex ([(11)C]PIB uptake 163% of the
      control mean) and posterior cingulate (146%) followed by the parietal (146%) and
      temporal (145%) cortices and striatum (133%), as well as small increases in the
      occipital cortex (117%) and thalamus (115%). CONCLUSIONS: Voxel-based analysis
      revealed widespread distribution of increased [(11)C]PIB uptake in Alzheimer
      disease (AD). These findings are in accordance with the distribution and phases
      of amyloid pathology in AD, previously documented in postmortem studies.

PMID- 16971698
TI  - Environmental lead exposure and cognitive function in community-dwelling older
      adults.
AB  - OBJECTIVE: To determine if long-term exposure to high levels of lead in the
      environment is associated with decrements in cognitive ability in older
      Americans. METHODS: We completed a cross-sectional analysis using multiple linear
      regression to evaluate associations of recent (in blood) and cumulative (in
      tibia) lead dose with cognitive function in 991 sociodemographically diverse,
      community-dwelling adults, aged 50 to 70 years, randomly selected from 65
      contiguous neighborhoods in Baltimore, MD. Tibia lead was measured with (109)Cd
      induced K-shell X-ray fluorescence. Seven summary measures of cognitive function
      were created based on standard tests in these domains: language, processing
      speed, eye-hand coordination, executive functioning, verbal memory and learning,
      visual memory, and visuoconstruction. RESULTS: The mean (SD) blood lead level was
      3.5 (2.2) microg/dL and tibia lead level was 18.7 (11.2) microg/g. Higher tibia
      lead levels were consistently associated with worse cognitive function in all
      seven domains after adjusting for age, sex, APOE-epsilon4, and testing technician
      (six domains p <or= 0.01, one domain p <or= 0.05). Blood lead was not associated
      with any cognitive domain. Associations with tibia lead were attenuated after
      adjustment for years of education, wealth, and race/ethnicity. CONCLUSIONS:
      Independent of recent lead dose, retained cumulative dose resulting from previous
      environmental exposures may have persistent effects on cognitive function. A
      portion of age-related decrements in cognitive function in this population may be
      associated with earlier lead exposure.

PMID- 16971699
TI  - Infusion of platelets transiently reduces nucleoside overload in MNGIE.
AB  - Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is caused by
      thymidine phosphorylase (TP) deficiency, which leads to toxic accumulations of
      thymidine (dThd) and deoxyuridine (dUrd). In this work, we report that infusion
      of platelets from healthy donors to patients with MNGIE restored transiently
      circulating TP and reduced plasma dThd and dUrd levels, suggesting that
      treatments to achieve permanent restoration of circulating TP such as allogeneic
      stem cell transplantation or gene transfer might be therapeutic.

PMID- 16971700
TI  - Incidence of migraine relative to menstrual cycle phases of rising and falling
      estrogen.
AB  - OBJECTIVE: To investigate the association between urinary hormone levels and
      migraine, with particular reference to rising and falling levels of estrogen
      across the menstrual cycle in women with menstrual and menstrually related
      migraine. METHODS: Women with regular menstrual cycles, who were not using
      hormonal contraception or treatments and who experienced between one and four
      migraine attacks per month, one of which regularly occurred on or between days 1
      +/- 2 of menstruation, were studied for three cycles. Women used a fertility
      monitor to identify ovulation, conducting a test each day as requested by the
      monitor, using a sample of early morning urine. Urine samples were collected
      daily for assay of estrone-3-glucuronide, pregnanediol 3-glucuronide, follicle
      stimulating hormone, and luteinizing hormone. All women kept a daily migraine
      diary and continued their usual treatment for migraine. RESULTS: Of 40 women
      recruited, data from 38 women were available for analysis. Compared with the
      expected number of attacks, there was a significantly higher number of migraine
      attacks during the late luteal/early follicular phase of falling estrogen and
      lower number of attacks during rising phases of estrogen. CONCLUSION: These
      findings confirm a relationship between migraine and changing levels of estrogen,
      supporting the hypothesis of perimenstrual but not postovulatory estrogen
      "withdrawal" migraine. In addition, rising levels of estrogen appear to offer
      some protection against migraine.

PMID- 16971701
TI  - Significant Increase in TDE's 2005 Impact Factor.

PMID- 16971702
TI  - Join me and bold the e.

PMID- 16971703
TI  - Burger King and Subway: key nutrients, glycemic index, and glycemic load of
      nutritionally promoted items.
AB  - PURPOSE: The purpose of this investigation was to estimate the glycemic load (GL)
      of nutritionally promoted fast-food menu items and to compare menu items
      nutritionally. METHODS: Published glycemic index (GI) values and nutritional
      information from the Web sites of Subway and Burger King were used to calculate
      the GL of nutritionally promoted items. Menu items were compared based on
      calories, macronutrients, saturated fat, GI, and GL as basic items and as often
      served. RESULTS: Subway offered 7 low-fat (total/saturated fat: 3-5/1-2 g), low
      calorie (230-330) sandwich options that had an average GL of 29. If the customer
      accepts the soda and baked potato chips, the total calories exceed 600 and the
      total/saturated fat becomes 13/4 g, with a doubling of the GL. The Burger King
      low-fat options contained 4.5 g total fat and 1.5 g saturated fat, with GLs of 53
      to 54, and low-calorie options (265-310 calories) had low GLs (0-18.3). Adding
      fries and a soda brings the GL up from a 53 for just the sandwich to 123 for the
      meal. The bunless low-carb Whopper has the same fat content (total/saturated fat:
      42/13g) as the original Whopper, but the GI and GL are zero. CONCLUSIONS: The
      nutritional information for meal options available at Burger King and Subway can
      help the patient with diabetes make choices. Accepting the fries or chips and
      soda can dramatically increase the calories, carbohydrate, fat, and GL of the
      nutritionally promoted fast-food meal.

PMID- 16971704
TI  - Update in the pharmacologic treatment of diabetes mellitus: focus on pramlintide
      and exenatide.
AB  - There are now more than 20 million people in America with diabetes mellitus (DM),
      and the prevalence of this illness continues to increase especially in those with
      type 2 DM. Over the past decade, research in the area of DM treatment has focused
      on pharmacologic approaches to modifying glucose metabolism as well as on
      lifestyle interventions to prevent and manage DM. Pharmacologic research has been
      guided by an improved understanding of the human physiology of glucose
      metabolism, allowing for development of new hormonal drug therapies and improved
      insulin formulations. As a result, there are several new pharmacologic treatments
      now available or on the horizon for DM. In this article, the authors review the
      first of the new hormonal therapies for DM, with a focus on information that will
      be useful for diabetes educators including the medication actions, side effects,
      patient counseling points, monitoring, and place in therapy in comparison to
      existing DM treatments. This series on new therapies has been divided into 3
      parts, with this first part devoted to an update on the new incretin mimetic and
      amylin analog agents recently approved for use in DM. Subsequent parts in this
      series will focus on the new insulin products and oral therapies available or
      soon to be available. Cases will be used to assist with understanding the type of
      patient who will benefit from each of these new therapies.

PMID- 16971705
TI  - Training effective interpreters for diabetes care and education: a new challenge.
AB  - PURPOSE: This article describes a pilot project to improve knowledge, attitudes,
      and skills of ad hoc interpreters working with Native American diabetes patients
      with limited English proficiency. METHODS: Case-based studies reflecting clinical
      situations were developed. Key concepts and terms from the cases were translated
      into the Navajo language and carefully back translated using the newly
      standardized Navajo diabetes terminology. Twenty-two health care workers from 2
      Indian Health Service facilities were recruited for a pilot study to compare the
      performance of interpreters trained in a formal workshop using the case studies
      with that of interpreters who independently reviewed a video made from the
      training. RESULTS: Workshop participants noted significant improvements in their
      knowledge and comfort level in interpretation of diabetes concepts but not about
      unrelated topics; the independent study group perceived less improvement.
      CONCLUSION: Formal training for interpreters working with diabetes patients
      should be considered by diabetes educators working in settings where medical
      interpreters are needed. Diabetes educators should encourage back translation of
      key diabetes concepts to understand exactly what is being said to patients. Those
      working with multiple interpreters should make sure there are opportunities for
      interpreters to discuss translations of key concepts with each other and the
      educators so that translations are accurate and consistent among interpreters.
      Independent study did not appear to be an effective way to improve the ability of
      interpreters to translate current diabetes concepts accurately.

PMID- 16971706
TI  - Feasibility test of a shared care network for children with type 1 diabetes
      mellitus.
AB  - PURPOSE: The purpose of this feasibility study was to examine primary care
      pediatricians and a diabetes specialty team sharing the care of children with
      type 1 diabetes in a structured network. METHODS: A diabetes specialty team and 3
      pediatric practice groups participated in training and shared care of patients
      with type 1 diabetes. The diabetes team-consisting of 1 pediatric
      endocrinologist, 2 nurses in advanced practice, and 1 master's-prepared
      registered dietitian-initiated therapy and self-management training for families;
      pediatricians implemented maintenance therapy. Role definitions, specially
      developed records, and a communication framework guided the interaction of
      providers. Satisfaction of families and pediatricians was assessed by
      questionnaire. The A1C level was used to assess patients' metabolic control.
      RESULTS: Twenty-nine patients accepted pediatrician referral, 25 kept initial
      training sessions, and 20 completed at least 1 year in the network. All 24
      invited pediatricians participated, and 17 enrolled patients. All families who
      completed satisfaction surveys were highly satisfied with the network. Nineteen
      pediatricians completed end-of-study questions and were also highly positive
      about sharing care with the specialty team. The mean A1C value was near target
      levels or better the first year, and it rose during the second year. CONCLUSIONS:
      The study supports the feasibility of integrating general pediatrician and
      diabetes specialty services for children with type 1 diabetes. Larger studies are
      justified to assess the efficacy and effectiveness of shared care.

PMID- 16971707
TI  - Existing measures of diabetes-specific support for use with adolescents with
      diabetes.
AB  - PURPOSE: The purpose of this article is to review existing measures of diabetes
      specific support for use with adolescents with type 1 diabetes. METHODS: Diabetes
      specific support scales for use with adolescents with type 1 diabetes were
      reviewed in terms of the dimension of support measured as well as reported
      reliability and validity. RESULTS: The scales measure enacted and/or perceived
      support. However, various support categories are measured: supportive and
      nonsupportive by the Diabetes Family Behavior Checklist (DFBC); warmth and
      guidance/control by the Diabetes Family Behavior Scale (DFBS); instrumental,
      informational, companionship/belonging, and emotional by the Diabetes Social
      Support Interview (DSSI); insulin administration, glucose monitoring, meals,
      exercise, and emotional support by the Diabetes Social Support Questionnaire
      Family Version (DSSQ-Family) and the Diabetes Social Support Questionnaire
      Friends Version (DSSQ-Friends); and guidance for autonomy development by the
      Diabetes-Specific Parental Support for Adolescents' Autonomy Scale (DPSAAS). The
      DSSI, DSSQ-Family, DSSQ-Friends, the DFBS, and DPSAAS have adequate reliability.
      Predictive validity is suggested in that diabetes management was related to the
      DFBC supportive subscale, the DSSI, the DSSQ-Family, and the DSSQ-Friends;
      metabolic control was related to the DFBS total score and guidance subscale; and
      diabetes management responsibility was related to the DPSAAS. CONCLUSIONS: Health
      care professionals need to decide which aspects of support are relevant to
      measure in their specific situation.

PMID- 16971708
TI  - Tomando Control: a culturally appropriate diabetes education program for Spanish
      speaking individuals with type 2 diabetes mellitus--evaluation of a pilot
      project.
AB  - PURPOSE: The purpose of this study was to pilot test the feasibility,
      acceptability, and efficacy of a culturally appropriate and culturally relevant
      Spanish-language cognitive-behavioral diabetes self-care educational intervention
      for Hispanic Americans with type 2 diabetes mellitus. METHODS: The study site was
      an urban community health center in the Northeast, at which 16 Latino patients
      with type 2 diabetes mellitus were recruited. This was a 1-group pretest-posttest
      pilot study, during which qualitative and quantitative data were collected on
      demographic, physiologic (HbA1c, body mass index, lipids), psychosocial (diabetes
      related distress and health beliefs), knowledge, and language-based acculturation
      variables at baseline, 3 months, and 6 months. Data were collected using
      questionnaires, laboratory data, and chart review. The intervention was
      culturally appropriate in terms of language, social emphasis, nutritional
      guidance, and acknowledgment of cultural health beliefs. Descriptive and
      inferential statistical analysis was used to evaluate response variables of
      glycemic control, lipid levels, and psychosocial and knowledge outcomes. The
      intervention acceptability process was evaluated by attendance and attrition.
      RESULTS: This pilot study demonstrated excellent acceptance for and feasibility
      of this intervention. Most study participants (9 women, 7 men) were middle-aged
      married individuals who had had diabetes mellitus for an average of 8 years;
      English was a second language for all of them. Most were overweight and had
      suboptimal glycemic control and lipid profiles and moderate levels of knowledge
      at the outset of the study. Most had received a one-on-one diabetes educational
      session prior to the intervention. Over the 6 months of the study, most of both
      men and women showed an increase in knowledge scores, improvement in lipid
      profiles, and reduction in HbA1c levels. Men demonstrated a temporary increase in
      emotional distress much greater than that reported by women during the first 3
      months of the study. CONCLUSIONS: The findings suggest that a culturally relevant
      type 2 diabetes mellitus educational program, particularly one that addresses
      different learning needs and styles of men and women, can have a positive impact
      on Hispanic Americans with diabetes. Implications for practice include awareness
      of gender-based differences in response to self-management education, the
      importance of providing realistic samples of meals prepared in a manner
      consistent with American Diabetes Association principles, and the rationale for
      offering a brief and focused refresher course 6 to 9 months following this type
      of intervention.

PMID- 16971709
TI  - Economic analysis of the Mediterranean Lifestyle Program for postmenopausal women
      with diabetes.
AB  - PURPOSE: The purpose of this study was to evaluate costs associated with the
      primary intervention of the Mediterranean Lifestyle Program (MLP), which targeted
      postmenopausal women with type 2 diabetes at risk for coronary heart disease.
      METHODS: Using retrospective data collected during MLP development and
      implementation, the authors estimated costs for the first 6 months relative to
      the usual care condition and incremental costs per behavioral, biologic, and
      quality-of-life change. Sensitivity analyses were conducted using variations in
      inflation rates, implementation settings, labor and nonlabor inputs, and market
      wage rates. RESULTS: Of the sample of 279 study participants, 163 were randomized
      into the MLP condition. Total intervention costs were estimated at $211 061 ($148
      022 direct costs) or $1295 per MLP participant relative to usual care ($908
      direct costs). This translates to $3808 per average change in coronary heart
      disease risk as measured by an average 1-point reduction in hemoglobin A1C.
      Relative to other measured improvements, this corresponds to $2345 per unit
      reduction in body mass index and $644 per unit improvement in Problem Areas in
      Diabetes Quality-of-Life Self-care Summary score, and a $196 per-gram reduction
      in intake of saturated fatty acids as noted by the Food Frequency Questionnaire.
      A significant portion of the direct costs were related to the resources used
      during the recruitment phase. CONCLUSIONS: Providing a relatively intensive
      lifestyle self-management program for this high-risk group is associated with
      modest incremental costs compared with usual care, making the program potentially
      appealing to policy makers.

PMID- 16971710
TI  - Patient perceptions of satisfaction following diabetes education: use of the
      mastery of stress instrument.
AB  - PURPOSE: The purpose of this study was to test the conceptual congruency of
      scores from the Mastery of Stress Instrument (MSI) with qualitative data in an
      effort to identify patients for whom a specific educational intervention was
      sufficient. METHODS: A convenience sample of patients with diverse age and
      educational backgrounds was recruited from those who registered for a 4-session
      diabetes educational experience as new or refresher patients. All 57 patients
      completed the MSI before and after diabetes educational experiences, and half
      participated in before and after audiotaped interviews. All patients responded to
      a query about their perceptions of the educational experience. MSI scores were
      analyzed by demographic variables as well as compared to qualitative interviews
      for greater insights and explanation. RESULTS: Consistency was noted between the
      MSI scores and the information revealed in the interviews. Additional support for
      the use of the MSI to identify patients at risk and in need of additional
      educational interventions was realized. CONCLUSIONS: Further research to explore
      the use of the MSI with persons with different educational experiences and to
      standardize the MSI scores for adult persons taking diabetes or other patient
      education classes is needed before generalization can be achieved.

PMID- 16971711
TI  - Social support, self-efficacy, and outcome expectations: impact on self-care
      behaviors and glycemic control in Caucasian and African American adults with type
      2 diabetes.
AB  - PURPOSE: The purpose of this study was to examine the relationships of
      psychosocial variables (social support, self-efficacy, and outcome expectations)
      to diabetes self-care behaviors and glycemic control in Caucasian and African
      American adults with type 2 diabetes. METHODS: Study participants were scheduled
      for outpatient visits at 1 of 3 clinical sites in the southeastern United States.
      All 91 participants completed 4 self-report measures: Social Support
      Questionnaire (SSQ), Self-efficacy Questionnaire (SEQ), Outcome Expectancy
      Questionnaire (OEQ), and The Diabetes Activities Questionnaire (TDAQ) at the time
      of the clinic visit. Long-term glycemic control was assessed by glycosylated
      hemoglobin analyses at the time of the clinic visit. Pearson product-moment
      correlations were used to determine whether significant relationships existed
      between scores on the SSQ, SEQ, OEQ, and TDAQ and glycosylated hemoglobin values.
      Two-sample t tests were used to detect differences in scores on the self-report
      measures and glycosylated hemoglobin values between the 2 racial groups. RESULTS:
      In all participants, no significant relationships were found between (1) social
      support and self-care behaviors and (2) self-efficacy and self-care behaviors.
      Self-care behaviors were significantly, positively correlated with outcome
      expectancy scores for the total group and for African Americans. No significant
      relationships were found between (1) social support and glycemic control, (2)
      self-efficacy and glycemic control, and (3) outcome expectations and glycemic
      control. African Americans reported less social support satisfaction than
      Caucasians did. CONCLUSIONS: Psychosocial variables investigated in this study
      were not related to health outcomes of type 2 diabetes. Caucasians and African
      Americans were similar in these variables. It is important to investigate the
      relationships between other variables (eg, age, duration of diabetes, education)
      and self-care behaviors and glycemic control. Although African Americans
      experience higher rates of diabetes-related complications than Caucasians do,
      this may possibly be due to other factors (eg, heredity, financial barriers,
      inadequate health care). Additional investigations to study the relationships of
      these variables to diabetes control are warranted.

PMID- 16971712
TI  - Images in clinical medicine. Elevated jugular venous pressure.

PMID- 16971713
TI  - Message from Toronto--deliver AIDS treatment and prevention.

PMID- 16971714
TI  - Global health--the Gates-Buffett effect.

PMID- 16971715
TI  - Fingolimod and sphingosine-1-phosphate--modifiers of lymphocyte migration.

PMID- 16971716
TI  - Sirolimus-eluting versus uncoated stents in acute myocardial infarction.
AB  - BACKGROUND: Sirolimus-eluting stents reduce rates of restenosis and
      reintervention, as compared with uncoated stents. Data are limited regarding the
      safety and efficacy of such stents in primary percutaneous coronary intervention
      (PCI) for acute myocardial infarction with ST-segment elevation. METHODS: We
      performed a single-blind, multicenter, prospectively randomized trial to compare
      sirolimus-eluting stents with uncoated stents in primary PCI for acute myocardial
      infarction with ST-segment elevation. The trial included 712 patients at 48
      medical centers. The primary end point was target-vessel failure at 1 year after
      the procedure, defined as target-vessel-related death, recurrent myocardial
      infarction, or target-vessel revascularization. A follow-up angiographic substudy
      was performed at 8 months among 174 patients from selected centers. RESULTS: The
      rate of the primary end point was significantly lower in the sirolimus-stent
      group than in the uncoated-stent group (7.3% vs. 14.3%, P=0.004). This reduction
      was driven by a decrease in the rate of target-vessel revascularization (5.6% and
      13.4%, respectively; P<0.001). There was no significant difference between the
      two groups in the rate of death (2.3% and 2.2%, respectively; P=1.00),
      reinfarction (1.1% and 1.4%, respectively; P=1.00), or stent thrombosis (3.4% and
      3.6%, respectively; P=1.00). The degree of neointimal proliferation, as assessed
      by the mean (+/-SD) in-stent late luminal loss, was significantly lower in the
      sirolimus-stent group (0.14+/-0.49 mm, vs. 0.83+/-0.52 mm in the uncoated stent
      group; P<0.001). CONCLUSIONS: Among selected patients with acute myocardial
      infarction, the use of sirolimus-eluting stents significantly reduced the rate of
      target-vessel revascularization at 1 year. (ClinicalTrials.gov number,
      NCT00232830 [ClinicalTrials.gov].).

PMID- 16971717
TI  - Paclitaxel-eluting versus uncoated stents in primary percutaneous coronary
      intervention.
AB  - BACKGROUND: Drug-eluting coronary-artery stents have been shown to decrease
      restenosis and therefore the likelihood that additional procedures will be
      required after percutaneous coronary intervention (PCI). We evaluated the use of
      a drug-eluting stent in patients undergoing PCI for acute myocardial infarction
      with ST-segment elevation. METHODS: We randomly assigned 619 patients presenting
      with an acute myocardial infarction with ST-segment elevation to receive either a
      paclitaxel-eluting stent or an uncoated stent. The primary end point was a
      composite of death from cardiac causes, recurrent myocardial infarction, or
      target-lesion revascularization at 1 year. RESULTS: Baseline clinical and
      angiographic characteristics in both groups were well matched. There was a trend
      toward a lower rate of serious adverse events in the paclitaxel-stent group than
      in the uncoated-stent group (8.8% vs. 12.8%; adjusted relative risk, 0.63; 95%
      confidence interval, 0.37 to 1.07; P=0.09). A nonsignificant trend was also
      detected in favor of the paclitaxel-stent group, as compared with the uncoated
      stent group, in the rate of death from cardiac causes or recurrent myocardial
      infarction (5.5% vs. 7.2%, P=0.40) and in the rate of target-lesion
      revascularization (5.3% vs. 7.8%, P=0.23). The incidence of stent thrombosis
      during 1 year of follow-up was the same in both groups (1.0%). CONCLUSIONS:
      Although the use of paclitaxel-eluting stents in acute myocardial infarction with
      ST-segment elevation reduced the incidence of serious adverse cardiac events at 1
      year by 4.0 percentage points, as compared with uncoated stents, the difference
      was not statistically significant. (Current Controlled Trials number,
      ISRCTN65027270 [controlled-trials.com].).

PMID- 16971718
TI  - Chemotherapy with preoperative radiotherapy in rectal cancer.
AB  - BACKGROUND: Preoperative radiotherapy is recommended for selected patients with
      rectal cancer. We evaluated the addition of chemotherapy to preoperative
      radiotherapy and the use of postoperative chemotherapy in the treatment of rectal
      cancer. METHODS: We randomly assigned patients with clinical stage T3 or T4
      resectable rectal cancer to receive preoperative radiotherapy, preoperative
      chemoradiotherapy, preoperative radiotherapy and postoperative chemotherapy, or
      preoperative chemoradiotherapy and postoperative chemotherapy. Radiotherapy
      consisted of 45 Gy delivered over a period of 5 weeks. One course of chemotherapy
      consisted of 350 mg of fluorouracil per square meter of body-surface area per day
      and 20 mg of leucovorin per square meter per day, both given for 5 days. Two
      courses were combined with preoperative radiotherapy in the group receiving
      preoperative chemoradiotherapy and the group receiving preoperative
      chemoradiotherapy and postoperative chemotherapy; four courses were planned
      postoperatively in the group receiving preoperative radiotherapy and
      postoperative chemotherapy and the group receiving preoperative chemoradiotherapy
      and postoperative chemotherapy. The primary end point was overall survival.
      RESULTS: We enrolled 1011 patients in the trial. There was no significant
      difference in overall survival between the groups that received chemotherapy
      preoperatively (P=0.84) and those that received it postoperatively (P=0.12). The
      combined 5-year overall survival rate for all four groups was 65.2%. The 5-year
      cumulative incidence rates for local recurrences were 8.7%, 9.6%, and 7.6% in the
      groups that received chemotherapy preoperatively, postoperatively, or both,
      respectively, and 17.1% in the group that did not receive chemotherapy (P=0.002).
      The rate of adherence to preoperative chemotherapy was 82.0%, and to
      postoperative chemotherapy was 42.9%. CONCLUSIONS: In patients with rectal cancer
      who receive preoperative radiotherapy, adding fluorouracil-based chemotherapy
      preoperatively or postoperatively has no significant effect on survival.
      Chemotherapy, regardless of whether it is administered before or after surgery,
      confers a significant benefit with respect to local control. (ClinicalTrials.gov
      number, NCT00002523 [ClinicalTrials.gov].).

PMID- 16971719
TI  - Oral fingolimod (FTY720) for relapsing multiple sclerosis.
AB  - BACKGROUND: Fingolimod (FTY720) is a new oral immunomodulating agent under
      evaluation for the treatment of relapsing multiple sclerosis. METHODS: We
      randomly assigned 281 patients to receive oral fingolimod, at a dose of 1.25 mg
      or 5.0 mg, or a placebo once daily, and we followed these patients for 6 months
      with magnetic resonance imaging (MRI) and clinical evaluations (core study,
      months 0 to 6). The primary end point was the total number of gadolinium-enhanced
      lesions recorded on T(1)-weighted MRI at monthly intervals for 6 months. In an
      extension study in which the investigators and patients remained unaware of the
      dose assignments (months 7 to 12), patients who received placebo underwent
      randomization again to one of the fingolimod doses. RESULTS: A total of 255
      patients completed the core study. The median total number of gadolinium-enhanced
      lesions on MRI was lower with 1.25 mg of fingolimod (1 lesion, P<0.001) and 5.0
      mg of fingolimod (3 lesions, P=0.006) than with placebo (5 lesions). The
      annualized relapse rate was 0.77 in the placebo group, as compared with 0.35 in
      the group given 1.25 mg of fingolimod (P=0.009) and 0.36 in the group given 5.0
      mg of fingolimod (P=0.01). For the 227 patients who completed the extension
      study, the number of gadolinium-enhanced lesions and relapse rates remained low
      in the groups that received continuous fingolimod, and both measures decreased in
      patients who switched from placebo to fingolimod. Adverse events included
      nasopharyngitis, dyspnea, headache, diarrhea, and nausea. Clinically asymptomatic
      elevations of alanine aminotransferase levels were more frequent with fingolimod
      (10 to 12%, vs. 1% in the placebo group). One case of the posterior reversible
      encephalopathy syndrome occurred in the 5.0-mg group. Fingolimod was also
      associated with an initial reduction in the heart rate and a modest decrease in
      the forced expiratory volume in 1 second. CONCLUSIONS: In this proof-of-concept
      study, fingolimod reduced the number of lesions detected on MRI and clinical
      disease activity in patients with multiple sclerosis. Evaluation in larger,
      longer-term studies is warranted. (Clinicaltrials.gov numbers, NCT00333138 [core
      study] and NCT00235430 [ClinicalTrials.gov] [extension].).

PMID- 16971720
TI  - Cost-effectiveness of HIV treatment in resource-poor settings--the case of Cote
      d'Ivoire.
AB  - BACKGROUND: As antiretroviral therapy is increasingly used in settings with
      limited resources, key questions about the timing of treatment and use of
      diagnostic tests to guide clinical decisions must be addressed. METHODS: We
      assessed the cost-effectiveness of treatment strategies for a cohort of adults in
      Cote d'Ivoire who were infected with the human immunodeficiency virus (HIV) (mean
      age, 33 years; CD4 cell count, 331 per cubic millimeter; HIV RNA level, 5.3 log
      copies per milliliter). Using a computer-based simulation model that incorporates
      the CD4 cell count and HIV RNA level as predictors of disease progression, we
      compared the long-term clinical and economic outcomes associated with no
      treatment, trimethoprim-sulfamethoxazole prophylaxis alone, antiretroviral
      therapy alone, and prophylaxis with antiretroviral therapy. RESULTS: Undiscounted
      gains in life expectancy ranged from 10.7 months with antiretroviral therapy and
      prophylaxis initiated on the basis of clinical criteria to 45.9 months with
      antiretroviral therapy and prophylaxis initiated on the basis of CD4 testing and
      clinical criteria, as compared with trimethoprim-sulfamethoxazole prophylaxis
      alone. The incremental cost per year of life gained was 240 dollars (in 2002 U.S.
      dollars) for prophylaxis alone, 620 dollars for antiretroviral therapy and
      prophylaxis without CD4 testing, and 1,180 dollars for antiretroviral therapy and
      prophylaxis with CD4 testing, each compared with the next least expensive
      strategy. None of the strategies that used antiretroviral therapy alone were as
      cost-effective as those that also used trimethoprim-sulfamethoxazole prophylaxis.
      Life expectancy was increased by 30% with use of a second line of antiretroviral
      therapy after failure of the first-line regimen. CONCLUSIONS: A strategy of
      trimethoprim-sulfamethoxazole prophylaxis and antiretroviral therapy, with the
      use of clinical criteria alone or in combination with CD4 testing to guide the
      timing of treatment, is an economically attractive health investment in settings
      with limited resources.

PMID- 16971721
TI  - Echinocandins for candidemia in adults without neutropenia.

PMID- 16971722
TI  - Images in clinical medicine. Radiographic appearance of lanthanum.

PMID- 16971723
TI  - Case records of the Massachusetts General Hospital. Case 28-2006. A 59-year-old
      man with masses in both kidneys.

PMID- 16971724
TI  - Drug-eluting stents in acute myocardial infarction.

PMID- 16971725
TI  - A critical new pathway for toxin secretion?

PMID- 16971726
TI  - Cyclophosphamide in scleroderma lung disease.

PMID- 16971727
TI  - Fluid-management strategies in acute lung injury.

PMID- 16971728
TI  - Thyroxine in goiter, H. pylori infection, and gastritis.

PMID- 16971729
TI  - Male urethral catheterization.

PMID- 16971730
TI  - Idiopathic short stature.

PMID- 16971731
TI  - Patient-specific dendritic-cell vaccines for metastatic melanoma.

PMID- 16971732
TI  - Heritability and genetic loci of fatty liver in familial combined hyperlipidemia.
AB  - VLDL overproduction, a process that is driven by an excess amount of hepatic fat,
      is a well-documented feature of familial combined hyperlipidemia (FCHL). The aims
      of this study were to investigate whether fatty liver, measured with ultrasound
      and as plasma alanine aminotransferase (ALT) levels, develops against a genetic
      background in FCHL and to identify chromosomal loci that are linked to these
      traits. In total, 157 FCHL family members and 20 spouses participated in this
      study. Radiological evidence of fatty liver was more prevalent not only in FCHL
      probands (40%) but also in their relatives (35%) compared with spouses (15%) (P <
      0.05). Heritability calculations revealed that 20-36% of the variability in ALT
      levels could be attributed to genetic factors. Nonparametric quantitative trait
      locus (QTL) analysis revealed three significant (P < 0.001) loci with either the
      ultrasound or the ALT trait in the male sample: 1q42.3, 7p12-21, and 22p13-q11;
      none was found in the female sample or the entire group. Of these QTLs, the 7p
      region was consistent over time, because reanalysis with ALT levels that were
      determined during a visit 5 years earlier yielded similar results. This study
      shows that fatty liver is a heritable aspect of FCHL. Replication of particularly
      the 7p region is awaited.

PMID- 16971733
TI  - What are the current standards of care and recent developments in the management
      of breast cancer?

PMID- 16971734
TI  - Adjuvant trastuzumab: a milestone in the treatment of HER-2-positive early breast
      cancer.
AB  - Up to one fourth of women diagnosed with early breast cancer (EBC) have tumors
      that are human epidermal growth factor receptor 2 (HER-2) positive. This is
      associated with a high risk of relapse and death from meta-static disease.
      Trastuzumab, a monoclonal antibody directed against the extracellular domain of
      HER-2, improves survival and quality of life in women with HER-2-positive
      metastatic breast cancer receiving chemotherapy. Four major adjuvant trials
      Herceptin Adjuvant (HERA), National Surgical Adjuvant Breast and Bowel Project
      (NSABP) B-31, North Central Cancer Treatment Group (NCCTG) N9831, and Breast
      Cancer International Research Group (BCIRG) 006-including between them >13,000
      women with HER-2-positive EBC, have investigated different adjuvant treatment
      approaches with trastuzumab. These trials have shown that trastuzumab reduces the
      3-year risk of recurrence by about half in this population. The benefit was
      similar across the trials despite differences in patient populations,
      chemotherapy regimens, and sequencing of treatment. At a 2-year follow-up,
      interim results from the combined analysis of the NSABP B-31 and NCCTG N9831
      trials showed a one third lower mortality for trastuzumab, and there was a trend
      toward an overall survival benefit in the HERA and BCIRG trials. A small Finnish
      trial, FinHer, investigating another regimen of trastuzumab, has also shown
      similarly positive results. Further follow-up of the major adjuvant trials will
      clarify the survival benefit for women receiving trastuzumab, as well as the
      optimal treatment duration (1 or 2 years). Notably, cardiac events in the
      trastuzumab-containing arms of these trials have remained within acceptable
      levels, with a slightly higher (0.6%-3.3%) incidence of congestive heart failure
      that mostly responded to treatment. Further follow-up will provide information on
      long-term cardiac safety. Overall, results from clinical trials are sufficiently
      compelling to consider 1 year of adjuvant trastuzumab treatment for women with
      HER-2-positive EBC based on the risk:benefit ratio demonstrated in these studies.

PMID- 16971735
TI  - The role of bisphosphonates in early breast cancer.
AB  - Clinical trials are investigating the use of bisphosphonates in patients with
      early (nonmetastatic) breast cancer. Results from trials of clodronate are
      generally encouraging but somewhat contradictory. Of the three trials published
      to date, two reported that clodronate had beneficial effects on both bone
      metastases and survival. In contrast, the third trial reported that clodronate
      had no effect on metastases and a negative effect on survival. Small studies of
      adjuvant pamidronate and zoledronic acid also produced promising data, but these
      need to be reproduced in a large-scale, randomized trial setting before
      clinically meaningful conclusions can be drawn. A number of adjuvant trials are
      in progress to further evaluate the role of oral clodronate and i.v. zoledronic
      acid and to examine the effects of the newer bisphosphonate, ibandronate (oral
      formulation), in this setting. One of these trials is the joint Southwest
      Oncology Group/Intergroup/National Surgical Adjuvant Breast and Bowel Project
      trial, which is designed to compare the efficacy and safety of all three of these
      bisphosphonates in approximately 6,000 women with early breast cancer. Patient
      preference for oral or i.v. therapy will also be assessed.

PMID- 16971736
TI  - Capecitabine: expanding options for the treatment of patients with early or
      locally advanced breast cancer.
AB  - Capecitabine has proven efficacy in metastatic breast cancer, extending survival
      in combination with docetaxel and offering a favorable safety profile, including
      minimal myelosuppression and alopecia, as a single agent. It is therefore logical
      that capecitabine could build on the improved outcomes achieved with taxanes in
      early breast cancer. In the neoadjuvant setting, a phase III trial of
      capecitabine and docetaxel (XT) versus doxorubicin and cyclophosphamide (AC)
      showed that XT was more effective than AC in terms of clinical response rate and
      pathologic complete response rate, with a manageable safety profile. Other
      studies, including a phase III trial of capecitabine, epirubicin, and docetaxel,
      a phase III trial of capecitabine and vinorelbine, and several phase II studies
      of different regimens with capecitabine, have confirmed the high activity of
      neoadjuvant capecitabine, with acceptable safety. In the adjuvant setting, a
      Finnish phase III study (FinXX) of sequential XT followed by cyclophosphamide,
      epirubicin, and capecitabine versus docetaxel followed by 5-fluorouracil,
      epirubicin, and cyclophosphamide has shown favorable safety with lower doses of
      both capecitabine and docetaxel in the XT combination. Efficacy results from that
      trial are eagerly awaited. A large, ongoing trial program is continuing to
      explore the potential for capecitabine in the treatment of early breast cancer,
      looking at capecitabine-taxane combinations, capecitabine maintenance therapy,
      capecitabine for elderly patients, and sequential versus combination therapy,
      involving >20,000 patients.

PMID- 16971737
TI  - Ibandronate: its role in metastatic breast cancer.
AB  - Bisphosphonates are the most effective agents for treating and/or preventing
      complications of bone metastases and are the standard of care in this setting.
      Currently, four bisphosphonates are available for metastatic bone disease (MBD):
      clodronate, pamidronate, zoledronic acid, and ibandronate. Although all four of
      these bisphosphonates have been shown to reduce the incidence of skeletal-related
      events in patients with bone metastases, there are substantial differences among
      these agents in their potency, dose and route of administration, and side
      effects. Ibandronate and zoledronic acid, the two newer aminobisphosphonates,
      appear to have similar biochemical efficacies when phase III trial data are
      compared. Both agents were equally effective in reducing markers of bone
      resorption in the only prospective comparative trial carried out to date, but no
      data on relative clinical efficacy are available from head-to-head comparisons.
      Both the oral and i.v. formulations of ibandronate have also shown long-term
      efficacy in managing metastatic bone pain (MBP), but the onset of action of
      standard bisphosphonate treatment is not sufficient when rapid relief of pain is
      required. Because of its favorable renal safety profile, i.v. ibandronate can be
      administered daily for 3 days, as a so-called "loading dose." This dosing regimen
      has allowed rapid and effective relief of MBP without the unwanted side effects
      associated with opioids and other analgesics. Ibandronate is thus an effective,
      flexible, and well-tolerated bisphosphonate that can meet the varying
      requirements of patients with MBD.

PMID- 16971738
TI  - HER-2-positive metastatic breast cancer: optimizing trastuzumab-based therapy.
AB  - Trastuzumab with a taxane as first-line therapy is now the standard of care for
      patients with human epidermal growth factor receptor 2 (HER-2)-positive
      metastatic breast cancer (MBC). The search for additional and more effective
      trastuzumab-based therapies continues. Novel combinations of trastuzumab with
      chemotherapeutic agents, including vinorelbine, gemcitabine, and capecitabine,
      and hormonal therapy agents, such as tamoxifen and aromatase inhibitors, are
      currently under investigation in clinical trials. Available data suggest these
      combinations will provide additional treatment options that may ultimately lead
      to better outcomes for patients with HER-2-positive MBC. Evidence is growing for
      the use of trastuzumab treatment beyond disease progression and retreatment after
      (neo)adjuvant relapse is being explored to assist in clinical decision making.
      Already, the use of trastuzumab in the metastatic setting has changed HER-2
      positive status from a marker of poor prognosis to one of better overall outcome,
      and ongoing studies should expand further the treatment options for patients with
      HER-2-positive MBC.

PMID- 16971739
TI  - The role of capecitabine in first-line treatment for patients with metastatic
      breast cancer.
AB  - Capecitabine is an important drug in the therapeutic armamentarium for metastatic
      breast cancer. A comprehensive worldwide clinical trial program involving >10,000
      patients with locally advanced and metastatic breast cancer has provided evidence
      for the current treatment strategies. On the basis of data demonstrating
      consistent activity across several trials in patients with heavily pretreated
      breast cancer, capecitabine was approved in the U.S. in 1998 for the treatment of
      patients with metastatic disease resistant to paclitaxel and anthracycline
      containing therapy, with later European Union approval for single-agent
      capecitabine in the metastatic setting. Capecitabine plus docetaxel (XT) was
      approved by the U.S. Food and Drug Administration for the treatment of metastatic
      breast cancer in 2001 on the basis of the large phase III trial comparing XT with
      docetaxel alone, which showed a survival advantage for combination therapy
      compared with single-agent therapy. This was shortly followed by European
      approval for the combination in metastatic breast cancer. The clinical utility of
      capecitabine in the management of breast cancer is supported by its convenient
      oral dosing schedule and favorable safety profile, as well as its excellent
      clinical activity in primary and metastatic breast cancer. Recently, clinical
      trials have studied single-agent capecitabine as first-line treatment and
      evaluated other capecitabine-containing combinations with cytotoxic and novel
      targeted agents.

PMID- 16971740
TI  - The influence of Zn on the deposition of HA on sol-gel derived bioactive glass.
AB  - To evaluate the influence of Zn on the formation of hydroxyapatite (HA), zinc
      containing glass 58S4Z was prepared by substitution of CaO with 4 wt% ZnO in 58S
      bioactive glass, and Zn-containing simulated body fluid (ZnSBF) was prepared as
      soaking fluid. During the soaking, all samples could induce the deposition of HA,
      but 58S4Z in SBF and 58S in ZnSBF showed lower formation rate of HA than 58S in
      SBF, which suggests that both the Zn in glass and the Zn2+ in soaking fluid
      retarded the deposition of HA. The ICP and EDS analysis results indicated that
      the main factor was the preferential reaction of Zn2+ with PO4(3-), which
      resulted in a decrease of the PO4(3-) concentration in soaking fluid and the
      nucleation of HA. Besides the inhibitory effect of Zn2+ in the soaking fluid, Zn
      in 58S4Z glass caused a lower release rate of Ca2+ in the initial soaking periods
      because of the lower CaO content as compared with 58S, and resulted in a lower
      nucleation rate of HA. The results suggested that small amount of Zn in bioactive
      glass retarded the nucleation of HA, but with the exhaustion of Zn2+ by PO4(3-),
      it did not affect the long-term deposition of HA in SBF.

PMID- 16971741
TI  - An investigation of the shear bond strength of compomer restorative material to
      enamel and dentine.
AB  - The aim of this study was to investigate the effect of one step adhesives on the
      shear bond strength of a compomer restorative material to both enamel and
      dentine. Human extracted teeth were used for the study. Ten samples were prepared
      for both enamel and dentine specimens for each of the five groups: Tooth, no
      etch, Prime and Bond NT (P+B NT); tooth, Non-Rinse Conditioner (NRC), P+B NT;
      tooth, NRC, Prime and Bond 2.1 (P+B 2.1); tooth, etch, P+B NT; tooth, etch, P+B
      2.1. The specimens were subjected to bond testing. The shear bond strength was
      measured using an Inston 1193 testing machine using a cross head speed of 1
      mm/minute. The specimens were tested to destruction. The results show that for
      the enamel specimens the highest bond strength was recorded for those specimens
      subjected to Etch, P+B 2.1 (22.1 MPa) and Etch P+B NT (20.0 MPa). The groups of
      specimens which did not undergo etching had very low bond strengths ranging from
      11.4 MPa for NRC, P+B 2.1, 8.5 MPa for NRC P+B NT to 6.9 MPa for P+B NT. For the
      dentine specimens, for all of the groups, the shear bond strengths were low.
      Those groups subjected to etching produced the highest values of 7.9 MPa for NRC
      P+B 2.1 with the lowest value of 6.1 MPa for NRC P+B NT. These bond strengths
      were significantly lower than those achieved for bonding to enamel. Prime and
      Bond NT and Prime and Bond 2.1, used in conjunction with acid etching, produce
      satisfactory bond strengths of compomer restorative material to enamel. Bond
      strengths to dentine were low.

PMID- 16971742
TI  - Bone response to titanium implants coated with thin sputtered HA film subject to
      hydrothermal treatment and implanted in the canine mandible.
AB  - Hydroxyapatite (HA) was coated onto titanium implants using radio frequency
      magnetron sputtering. The HA films were crystallized in an autoclave tube using
      low temperature hydrothermal treatment. The average film thickness on the implant
      was 1.1 microm. HA-coated and pure-titanium implants were inserted into canine
      mandibles for up to 24 weeks. Forty-eight implants were placed in eight beagles.
      After 2, 4, 12 and 24 weeks, implants were retrieved and prepared for
      histological observation, and the HA film thickness was determined using energy
      dispersive X-ray spectroscopy. Light microscopy revealed that, after two weeks,
      the bone response to the HA-coated implants was much better than to the pure
      titanium implants, and osteoblasts were observed at the bone-implant interface.
      After four weeks, the screw threads of the HA-coated implants were almost
      completely covered with bone. The HA film thickness rapidly decreased up to four
      weeks of implantation, then gently decreased, reaching 0.40+/-0.03 microm at the
      upper region of the implant after 12 weeks. That indicates that about 80% of the
      HA film had dissolved after 12 weeks of implantation. The rate of decrease in the
      HA film thickness was greater with increasing implant depth.

PMID- 16971743
TI  - The mode of bone conservation does not affect the architecture and the tensile
      properties of rat femurs.
AB  - The bone samples used in clinical and experimental trials must be the less
      damaged as possible to avoid alterations of their properties. However, the mode
      of storage might possibly alter the bone properties, particularly
      microarchitecture and strength. The aim of our study was to analyze the effects
      of deep-freezing and alcohol conservation techniques on the densitometric,
      microarchitectural and biomechanical parameters of rat femurs. The left femurs
      were elongated in uniaxial tension up to breakdown in order to calculate
      biomechanical parameters. The densitometric and microarchitectural properties of
      right femurs were evaluated using dual-energy X-ray absorptiometry and
      microcomputed tomography, respectively. Results showed no significant difference
      in the parameters investigated between deep-freezing, alcohol storage and fresh
      femurs when comparing each parameter separately. Therefore, one month storage in
      alcohol or deep-freezing seemed to induce no harmful effect on densitometric,
      microarchitectural and biomechanical parameters of rat femurs.

PMID- 16971744
TI  - The effect of interspinous ligament integrity on adjacent segment instability
      after lumbar instrumentation and laminectomy--an experimental study in porcine
      model.
AB  - Eight fresh porcine lumbar spines received a posterior instrumentation at L4-L5
      using pedicle screw-rod system. Each specimen was tested utilizing laminectomies
      of varying extent. Group A (Integrity) preserved the spinous process and
      interspinous ligament; Group B (Partial laminectomy) removed the inferior portion
      of L4 spinous process and preserved the interspinous ligament of L3-L4; Group C
      (Complete laminectomy) removed the entire L4 spinous process. Hydraulic testing
      machine was used to generate an increasing moment up to 8400 N mm in flexion and
      extension. The intervertebral displacement on the superior adjacent disc between
      L3-L4 was measured using an extensometer. Under extension, no significant
      difference in the intervertebral displacement was observed among three different
      models of laminectomy. However, under flexion, the intervertebral displacement on
      adjacent disc with complete laminectomy was statistically larger than those of
      integrity and partial laminectomies (P=0.000976 and P=0.0363, respectively). No
      difference was found between integrity and partial laminectomy groups (P>0.05).
      This study implies that an instrumented spine with integrity of posterior complex
      is less likely to develop adjacent instability than a spine with destruction of
      the anchoring point for supraspinous ligament.

PMID- 16971745
TI  - Detection of atherosclerosis using autoregressive modelling and principles
      component analysis to carotid artery Doppler signals.
AB  - The purpose of this study was to evaluate principal component analysis method to
      power spectral density acquired with autoregressive modeling (AR) of carotid
      artery Doppler signals. Carotid artery Doppler signals from patient with
      atherosclerosis and healthy subjects were recorded. Afterwards, power spectral
      densities of these signals were obtained using AR method. The basic differences
      between the healthy and patients were obtained with 1st principal component
      obviously. These results could be extrapolated to situations involving
      noninvasive measurement where PCA can be extremely time saving. As a result the
      patient and healthy groups are separated clearly from each other via an arbitrary
      power function y=ax with perfect accuracy resulting in a precision sensitivity
      and specificity of 100 percent and the use of PCA of physiological waveform is
      presented as a powerful method likely to be incorporated in future medical signal
      processing.

PMID- 16971746
TI  - Development of an enhanced leg muscle rehabilitation system.
AB  - This paper aims to develop an enhanced rehabilitation and assessment system for
      people with impaired leg muscles, and for people who need to improve their leg
      muscle function. Through interactive design and real time evaluation, medical
      staff can totally control the training situation for patients and therefore
      provide a better training program, so that overall a better treatment performance
      can be achieved. The system consists of four major parts. Sensory and signal
      conversion circuits convert the lever arm lengths and muscle strengths of the leg
      into a proper electronic signal and then deliver this to the computer. Then, the
      intelligent and interactive interface design lets a trainee complete the training
      process independently without the involvement of medical staff. In addition, the
      trainee can see the training results at the end of the training process on the
      computer screen. The training protection and evaluation mechanism effectively
      monitors the training situation, based on the individual status settings by the
      medical staff, and thus any further impairment can be avoided. The database
      management system is developed to store related personal data, system settings
      and training results, which can then be retrieved for control and assessment. In
      comparison to similar equipment the proposed system demonstrates a much better
      performance, particularly in system functions, accuracy, operation and costs.

PMID- 16971747
TI  - Effects of baseline serum levels of Se on markers of eccentric exercise-induced
      muscle injury.
AB  - Inflammation and oxidative stress have been implicated in the mechanism of
      eccentric exercise-induced muscle injury. This study examined whether baseline
      serum levels of selenium (Se), a trace element that participates in both
      antioxidant and anti-inflammatory systems, affects the overall response to
      injury. Thirteen males performed 36 maximal eccentric actions with the elbow
      flexors of the non-dominant arm on a motorized dynamometer. Venous blood samples
      were collected immediately before and after exercise at 2, 24, 48, 72 and 96
      hours. Established indicators of muscle damage such as maximum isometric torque
      (MIT), range of motion (ROM), relaxed arm angle (RANG), flexed arm angle (FANG),
      arm circumference (CIRC), muscle soreness and serum levels of creatine kinase
      (CK) and lactate dehydrogenase (LDH) were determined at the same time points.
      Baseline serum levels of Se were also measured. Complementary data regarding
      assessment of Se status were retrieved by the use of a semi-quantitative food
      frequency questionnaire. All measures changed significantly (p<0.05) after
      exercise. The main finding of this study was that baseline Se serum levels were
      associated inversely with CK, LDH and FANG and positively with MIT and ROM
      (p<0.05). These data suggest that beyond overt Se deficiency, suboptimal Se
      status possibly worsens muscle functional decrements subsequent to eccentric
      muscle contractions.

PMID- 16971748
TI  - Effect of herbal extract mixture on menopausal urinary incontinence in
      ovariectomized rats.
AB  - The decline of estrogen production after menopause is contributing factor to
      urinary incontinence (UI), and particularly stress urinary incontinence (SUI). We
      determined the preventive effects of herbal extract mixture (HEM) on UI in
      ovariectomized Sprague Dawley rats. Female 9-weeks old rats were ovariectomized
      and treated with HEM (2.2, 11, or 55 mg/kg/day) for 8 weeks. The index of urinary
      bladder weight to body weight in the HEM and non-ovariectomized and non-treated
      (SHAM) groups were slightly higher than the ovariectomized, non-treated group
      (OVX). The contraction index of acetylcholine to KCl on detrusor smooth muscle
      strips in the HEM groups showed a dose-dependent recovery. HEM treatment also
      significantly improved collagen levels, as shown by Masson trichrome staining, as
      well as hydroxyproline levels in the urinary bladder. Serum estradiol levels in
      the HEM groups were higher than the OVX group. In conclusion, HEM increased
      estradiol levels in serum and improved factors related to urinary incontinence.
      The improvements in estradiol levels were related to changes in urinary
      incontinence.

PMID- 16971749
TI  - An integrated database of flavonoids.
AB  - Flavonoids are polyphenolic compounds that occur ubiquitously in foods of plant
      origin. Some of these molecules exhibit various physiological activities. Among
      existing drugs, there are a huge number of compounds bearing a flavonoid-related
      skeleton. Because of the relevance for pharmaceutical research, it would be
      beneficial to collect these compounds into a database. Recently, various
      databases of chemicals were compiled to help biological and/or chemical research,
      but no comprehensive database of flavonoids with chemical structures and
      physicochemical parameters, supposedly related to their activity, is available
      yet. The aim of this research was to merge the information about flavonoids of
      plant origin and flavonoids used as medicines into a database. Moreover,
      predictions of activities against various targets were performed using a virtual
      screening procedure to demonstrate a possible application of the database for
      pharmaceutical research.

PMID- 16971750
TI  - 6-Gingerol prevents cisplatin-induced acute renal failure in rats.
AB  - BACKGROUND: Nephrotoxicity is a major complication and a dose limiting factor for
      cisplatin therapy. Recent evidence suggests that enhanced oxidative stress caused
      by oxygen-centered free radicals may contribute to the pathogenesis of cisplatin
      induced acute renal failure. 6-Gingerol is claimed to be a potent antioxidant.
      The present study was performed to explore the renoprotective potential of 6
      gingerol on cisplatin-induced oxidative stress and renal dysfunction. METHODS: 6
      Gingerol in dosages of 12.5, 25, 50 mg/kg was administered 2 days before and 3
      days after cisplatin administration. Renal injury was assessed by measuring serum
      creatinine, blood urea nitrogen, creatinine, urea clearance and serum nitrite
      levels. Renal oxidative stress was assessed by determining renal malondialdehyde
      levels, reduced glutathione levels and enzymatic activities of superoxide
      dismutase and catalase. RESULTS: A single dose of cisplatin resulted in marked
      renal oxidative and nitrosative stress and significantly deranged renal
      functions. 6-Gingerol treatment significantly and dose-dependently restored renal
      functions, reduced lipid peroxidation and enhanced the levels of reduced
      glutathione and activities of superoxide dismutase and catalase. CONCLUSIONS: The
      present study demonstrates the renoprotective potential of 6-gingerol against
      cisplatin-induced oxidative stress and renal dysfunction in rats. Hence, 6
      gingerol has a potential to be used as therapeutic adjuvant in cisplatin
      nephrotoxicity.

PMID- 16971751
TI  - Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA)
      administration in humans.
AB  - The effect of orally administrated gamma-aminobutyric acid (GABA) on relaxation
      and immunity during stress has been investigated in humans. Two studies were
      conducted. The first evaluated the effect of GABA intake by 13 subjects on their
      brain waves. Electroencephalograms (EEG) were obtained after 3 tests on each
      volunteer as follows: intake only water, GABA, or L-theanine. After 60 minutes of
      administration, GABA significantly increases alpha waves and decreases beta waves
      compared to water or L-theanine. These findings denote that GABA not only induces
      relaxation but also reduces anxiety. The second study was conducted to see the
      role of relaxant and anxiolytic effects of GABA intake on immunity in stressed
      volunteers. Eight acrophobic subjects were divided into 2 groups (placebo and
      GABA). All subjects were crossing a suspended bridge as a stressful stimulus.
      Immunoglobulin A (IgA) levels in their saliva were monitored during bridge
      crossing. Placebo group showed marked decrease of their IgA levels, while GABA
      group showed significantly higher levels. In conclusion, GABA could work
      effectively as a natural relaxant and its effects could be seen within 1 hour of
      its administration to induce relaxation and diminish anxiety. Moreover, GABA
      administration could enhance immunity under stress conditions.

PMID- 16971752
TI  - Antioxidative effects of Cinnamomi cassiae and Rhodiola rosea extracts in liver
      of diabetic mice.
AB  - Both Cinnamomi cassiae and Rhodiola rosea extracts are used as anti-diabetic folk
      medicines. Recently, increased oxidative stress was shown to play an important
      role in the etiology and pathogenesis of diabetes mellitus and its complications.
      This study was designed to examine the effects of Cinnamomi cassiae and Rhodiola
      rosea extracts on blood glucose, lipid peroxidation, the level of reduced
      glutathione and its related enzymes (glutathione reductase, glutathione S
      transferase), and the activity of the antioxidant enzymes (catalase, superoxide
      dismutase and glutathione peroxidase) in the liver of db/db mice. Diabetic
      C57BL/Ks db/db mice were used as experimental models. Mice were divided into
      control (n=10), Cinnamomi cassiae (200 mg/kg/day, n=10), and Rhodiola rosea (200
      mg/kg/day, n=10) treated groups for 12 weeks of treatment. These type II diabetic
      mice were used to investigate the effects of Cinnamomi cassiae and Rhodiola rosea
      on blood glucose, reduced glutathione, glutathione reductase, glutathione S
      transferase, glutathione peroxidase, lipid peroxidation, catalase and superoxide
      dismutase. Cinnamomi cassiae and Rhodiola rosea extracts significantly decreased
      on blood glucose, increased levels of reduced glutathione and the activities of
      glutathione reductase, glutathione S-transferase, glutathione peroxidase,
      catalase and superoxide dismutase in the liver. Extract treatment also
      significantly decreased lipid peroxidation. Cinnamomi cassiae and Rhodiola rosea
      extracts may be effective for correcting hyperglycemia and preventing diabetic
      complications.

PMID- 16971753
TI  - Braccio di Ferro: a new haptic workstation for neuromotor rehabilitation.
AB  - This technical note describes a new robotic workstation for neurological
      rehabilitation, shortly named Braccio di Ferro. It has been designed by having in
      mind the range of forces and the frequency bandwidth that characterize the
      interaction between a patient and a physical therapist, as well as a number of
      requirements that we think are essential for allowing a natural haptic
      interaction: back-driveability, very low friction and inertia, mechanical
      robustness, the possibility to operate in different planes, and an open software
      environment, which allows the operator to add new functionalities and design
      personalized rehabilitation protocols. Braccio di Ferro is an open system and, in
      the spirit of open source design, is intended to foster the dissemination of
      robot therapy. Moreover, its combination of features is not present in
      commercially available systems.

PMID- 16971754
TI  - Advanced image fusion algorithms for Gamma Knife treatment planning. Evaluation
      and proposal for clinical use.
AB  - Image fusion is a process of combining information from multiple sensors. It is a
      useful tool implemented in the treatment planning programme of Gamma Knife
      Radiosurgery. In this paper we evaluate advanced image fusion algorithms for
      Matlab platform and head images. We develop nine level grayscale image fusion
      methods: average, principal component analysis (PCA), discrete wavelet transform
      (DWT) and Laplacian, filter - subtract - decimate (FSD), contrast, gradient,
      morphological pyramid and a shift invariant discrete wavelet transform (SIDWT)
      method in Matlab platform. We test these methods qualitatively and
      quantitatively. The quantitative criteria we use are the Root Mean Square Error
      (RMSE), the Mutual Information (MI), the Standard Deviation (STD), the Entropy
      (H), the Difference Entropy (DH) and the Cross Entropy (CEN). The qualitative
      are: natural appearance, brilliance contrast, presence of complementary features
      and enhancement of common features. Finally we make clinically useful
      suggestions.

PMID- 16971755
TI  - A distributed environment for the integration of multiple high-performance
      decision support systems into clinical workflow.
AB  - Current studies conclude that clinical decision support systems can help reduce
      serious medical errors. The importance of Causal Probabilistic Networks (CPNs)
      for constructing such systems is already well-known. However, the computational
      complexity of probabilistic inference, which results in unacceptably high
      response times, can hinder acceptance and integration into clinician workflow.
      This paper investigates the optimization and parallelization potential of complex
      CPN-based medical decision support systems and evaluates the results of
      implementing a parallel, high performance version of an existing decision support
      system concerning proper antibiotic treatment therapy. Furthermore, it discusses
      distributed computing techniques for making multiple high performance decision
      support systems available at the time and location of decision making, by
      exploiting computing resources residing inside, as well as outside the hospital
      walls optimally.

PMID- 16971756
TI  - Communication protocol requirements of patient personal area networks for
      telemonitoring.
AB  - Continuous, remote monitoring of patients' healthcare condition, as this can be
      reflected by crucial vital signs supervision, is a key demand in modern
      healthcare provision. Towards the accomplishment of this requirement, the
      traditional solution of cabled sensors appears to have clear limitations and this
      is one of the ultimate causes of the proliferation of wireless medical sensor
      networks during last years. The modern trend towards this direction is the
      formulation of patient Personal Area Networks (pPANs), consisting of a wireless
      infrastructure of medical sensors, attached to patient's body, which lays the
      path for incessant telemonitoring of the person in mind, without discomforting
      them. The nature of data that these networks are set to handle, as well as the
      particular demands that patient telemonitoring services raise, necessitate for a
      thorough analysis of the design requirements of pPAN communication protocols, in
      order to outflank possible disadvantages appearing in protocols for different
      types of wireless sensor networks, without putting aside simplicity and
      feasibility factors. In the context of this paper, we intend to outline the most
      important requirements and design issues of a pPAN communication protocol, having
      as compass the main attributes of the most commonly used medical sensors and the
      typical functionality of these networks.

PMID- 16971757
TI  - Cost-effectiveness analysis of telemedical devices for pre-clinical traffic
      accident emergency rescue in Germany.
AB  - OBJECTIVES: The purpose of this study is to assess the cost-effectiveness (net
      costs per life year gained) of telemedical devices for pre-clinical traffic
      accident emergency rescue in Germany. METHODS: Two equipment versions of a
      telemedical device are compared from a societal perspective with the baseline in
      Germany, i.e. the non-application of telemedicine in emergency rescues. The
      analysis is based on retrospective statistical data covering a period of 10 years
      with discounted costs not adjusted for inflation. Due to the uncertainty of data,
      certain assumptions and estimates were necessary. The outcome is measured in
      terms of "life years gained" by reducing therapy-free intervals and improvements
      in first-aid provided by laypersons. RESULTS: The introduction of the basic
      equipment version, "Automatic Accident Alert", is associated with net costs per
      life year gained of euro 247,977 (at baseline assumptions). The full equipment
      version of the telemedical device would lead to estimated net costs of euro
      239,524 per life year gained. Multi-way sensitivity-analysis with best and worst
      case scenarios suggests that decreasing system costs would disproportionately
      reduce total costs, and that rapid market penetration would largely increase the
      system's benefit, while simultaneously reducing costs. CONCLUSION: The net costs
      per life year gained in the application of the two versions of the telemedical
      device for pre-clinical emergency rescue of traffic accidents are estimated as
      quite high. However, the implementation of the device as part of a larger
      European co-ordinated initiative is more realistic.

PMID- 16971758
TI  - Data entry workers perceptions and satisfaction response to the "stop and
      stretch" software program.
AB  - Cumulative Trauma Disorder (CTD) is a collection of chronic musculoskeletal
      disorders caused by frequent, sustained, and repetitive movements, most notably
      by computer usage at the workplace. A computer based break reminder program (Stop
      and Stretch) has been developed and installed to prevent CTDs caused by prolonged
      computer usage at the workplace. We investigated users' opinions to the Stop and
      Stretch program at their work place. 19 computer users were recruited as the
      subjects of the study. We conducted a survey after all the subjects used the Stop
      and Stretch program for one month. Among the nineteen subjects, 52.5% or 10
      noticed a difference of symptoms after using the program; 63.3% or 12 thought the
      program had positive effect on their productivity; 100% or all 19 thought the
      program was easy to follow; 100% or all 19 thought it was helpful; 94.7% or18
      were satisfied with the program; and the same value would recommend the program
      to others. When grouped into those who had prior experience with using stretch
      and exercise as part of their work routine15 subjects had no prior experience;
      and 14 participants within that group were satisfied or very satisfied with the
      program; 93.3% or 14 would recommend it to co-workers; and over half of those 15
      thought the program is easy to use. The study provided insight to the response to
      using "stretch break software" and provided indicators of satisfaction with the
      Stop and Stretch program and that the program had sufficient usability and
      acceptance within a workplace setting which might be applied in other work
      settings similar to these.

PMID- 16971759
TI  - Participatory ergonomic processes to reduce musculoskeletal disorders: summary of
      a Quebec experience.
AB  - This article critically reviews 11 participatory ergonomic interventions carried
      out in Quebec by the Occupational Health and Safety Research Institute (IRSST).
      In the introduction, the characteristics of the approach used are situated in
      relation to the literature on this subject. Based on the "Ergo team" formula, the
      approach aims to provide company personnel with the skills to analyze and correct
      hazardous workstations in relation to musculoskeletal disorders (MSD), using an
      analysis process that the researchers developed. Although isolated workstations
      were corrected, the process aims for more general impacts on the company. In the
      11 interventions, 40 work situations were analyzed, and in 31 cases, changes were
      implemented to reduce MSD risks. The most common changes dealt with the
      tools/equipment (77.4% and physical layouts (84%); changes involving work methods
      (29% and work organization (12.9%) were less common. The difficulties encountered
      in the interventions are summarized, and the possible impacts of the
      interventions on the organization and psychosocial factors are discussed. The
      authors then address the limitations of the paper and the factors that should be
      considered in evaluating such a participatory process. The authors conclude that
      the participatory process was successful in implementing changes in companies and
      that other studies are necessary for a better understanding of the process and
      its impacts.

PMID- 16971760
TI  - Musculoskeletal symptoms in support staff in a large telecommunication company.
AB  - PRIMARY OBJECTIVE: The primary objective of this study was to determine the
      extent and severity of the musculoskeletal problems in office workers in a
      telecommunication company. RESEARCH DESIGN: A questionnaire survey was conducted
      to assess the prevalence of musculoskeletal disorders' symptoms, their perceived
      intensity and interaction with ability to work among office workers. METHODS AND
      PROCEDURES: The Cornell Musculoskeletal Discomfort Questionnaire and Cornell Hand
      Discomfort Questionnaire developed by the Human Factors and Ergonomics Laboratory
      at Cornell University were used on a sample of 140 office workers in a
      telecommunication company. MAIN OUTCOMES AND RESULTS: Discomfort/pain/ache at the
      wrist level was reported by 86.5% for the left side and 95.5% for the right side.
      Additionally, discomfort/pain/ache was reported by 77.5% of the sample for neck
      and 31% of the sample for the left and 50% for the right shoulder region. At the
      hand site, the area in the distal proximity of the wrist was the most affected
      site being indicated in 90% of cases for left side and 95% of cases for the right
      side. CONCLUSIONS: An overview of problems associated with the body parts in
      office work may allow targeted prevention and intervention.

PMID- 16971761
TI  - Effect of immunomodulatory therapy and other factors on employment loss time in
      multiple sclerosis.
AB  - The factors that influence time missed from work among individuals diagnosed with
      multiple sclerosis were the focus of this study. Records of individuals who were
      employed and diagnosed with multiple sclerosis between the years 1999 and 2002
      (N=284) were examined for details pertaining to their medical claims.
      Multivariate regressions, controlling for demographic characteristics, type of
      immunomodulatory medication, and overall severity of illness, were used in the
      examination of the total number of days missed from work for any reason and those
      missed due to absenteeism, short-term disability, or worker's compensation.
      Results indicate that lost work time is affected by severity of illness, and type
      of immunomodulatory therapy. Comparing individuals treated with the specific
      immunomodulator glatiramer acetate, interferon beta-1a (intramuscular), or
      interferon beta-1b, to those who did not receive multiple sclerosis medications
      of this type; only glatiramer acetate was associated with significantly fewer
      days missed from work for short term disability (18.24 fewer days, P<0.03),
      worker's compensation (29.50 fewer days, P<0.04) or any reason (53.70 fewer days,
      P< 0.003).

PMID- 16971762
TI  - What is healthy work for women and men? - A case-control study of gender- and
      sector-specific effects of psycho-social working conditions on long-term sickness
      absence.
AB  - The aim of the study was to investigate the relevance of the demand-control model
      and social support in predicting long-term sickness absence (LTSA). Identifying
      gender- and sector- (private vs. public) specific patterns was in focus. The
      study uses a cross-sectional design with a case and a control group. The cases
      are a sample of 2 327 long-term sick listed (>60 days) and the controls are a
      Swedish population-based sample of 2 063. Data on sickness absence were retrieved
      from the Swedish national social insurance registers. Data on health, working and
      living conditions were gathered through a self-administered questionnaire. The
      results show that employed women have a notably higher risk for LTSA than
      employed men. High-strain jobs increase the odds for LTSA among both women and
      men. Active jobs were also associated with LTSA among women. The study confirms
      the demand-control model (job strain hypothesis) and social support and their
      associations with LTSA. However, the job strain hypothesis is more evident in the
      private sector. Active jobs with high psychological demands and high decision
      latitude seem to be problematic for many women, especially in the private sector.
      Thus, the active learning hypothesis receives no support for women in the Swedish
      working population in general.

PMID- 16971763
TI  - Lifestyle, harassment at work and self-assessed health of female flight
      attendants, nurses and teachers.
AB  - Health-related lifestyle, harassment at work, and self-assessed health of female
      flight attendants in comparison to that of female nurses and female primary
      school teachers were surveyed. A higher proportion of flight attendants than
      nurses or teachers were smokers, 26% vs. 15% and 17% respectively; and consumed
      alcohol at least once a week, 40% vs. 21% and 16%. Repeated sexual harassment at
      work was more common among the flight attendants, 31% vs. 8% and 4%; whereas
      bullying, physical violence and threats were less prevalent among the flight
      attendants (12%) than among nurses (19%). Flight attendants were on average
      somewhat taller, but weighed on average less, 63.8 kg vs. 72.4 kg and 72.7 kg
      respectively. Repeated exposure to sexual harassment, bullying, violence and
      threats was related to less physical and psychological well-being in all the
      groups. Teachers scored on average significantly lower than did the flight
      attendants on general health and physical well-being, while nurses did not.

PMID- 16971764
TI  - Risk of disability pension in relation to gender and age in a Swedish county; a
      12-year population based, prospective cohort study.
AB  - Residents of the county of Ostergotland, Sweden, who were 16-64 years of age in
      December 1984 and not pensioned (n=229,864), were followed in a prospective,
      cohort, study of data collected between 1985 and 1996. Using survival methods as
      the method of analysis, the likelihood of being granted a disability pension was
      14% for women, 11% for men, and increased with age. Women less than 54 years of
      age were at higher risk than men (P<0.001), 69% of disability pensions granted
      were full-time and 31% were part-time, more women received part-time pensions
      (P<0.001). Whether the differences observed are due to gender bias in social
      insurance practices, to disease patterns, to occupational and work-related
      factors, or to a cohort effect has yet to be determined.

PMID- 16971765
TI  - Overprotection and lowered expectations of persons with disabilities: the
      unforeseen consequences.
AB  - Lowered expectations and overprotection of the individual with a disability can
      cause lowered self esteem which can result in a life time of underachievement and
      failure to reach their full potential. Both lowered expectations and
      overprotection are forms of discrimination. Internalization of discrimination
      causes the person with a disability to believe that they are less capable than a
      person without a disability. Parents and care providers of children with
      disabilities may overprotect the child to shield them from harm; however this can
      actually cause more damage. Successful parenting skills are required to help
      children and adolescents develop a positive self concept and high self esteem.
      Guidelines have been developed to assist parents, educators and other
      professionals regarding the effects of overprotection and lowered expectations.

PMID- 16971766
TI  - Target groups for prevention of neck/shoulder and low back disorders: an
      exploratory cluster analysis of working and living conditions.
AB  - Musculoskeletal disorders (MSDs) have a multifactorial etiology. Therefore, a
      holistic approach to identifying target groups for primary/secondary prevention
      is essential. In this study, an exploratory person-oriented approach was applied,
      using cluster analysis of variables related to physical and psychosocial work
      conditions, and conditions in the private sphere, on a data set of 1,341 Swedish
      women and men who had not sought care for MSDs the 6 months preceding enrollment
      in the study. Three groups at risk and five "healthy" groups regarding MSDs were
      identified. Two of the risk groups had a strained situation regarding
      psychosocial work conditions or domestic/family conditions, respectively. The
      majority of individuals in these groups were women. The third risk group had a
      strained situation regarding both physical and psychosocial work conditions. This
      group consisted largely of men working in male-dominated jobs. The five healthy
      groups had low/moderate metabolic demands at work, and all of them having high
      proportions of subjects with moderate to high education, and fairly even
      distributions of men and women. In conclusion, the results indicate that gender
      specific working and living conditions are associated with an increased risk for
      MSDs. The identification of these subgroups in the population may facilitate a
      selective prevention approach.

PMID- 16971767
TI  - Simvastatin inhibits tissue factor and plasminogen activator inhibitor-1
      expression of glomerular mesangial cells in hypercholesterolemic rabbits.
AB  - Tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) activity and/or
      expression are upregulated in hypercholesterolemia. Despite extensive research on
      anti-thrombotic effect of statins, little is known about their effects on TF and
      PAI-1 expression in glomerular mesangial cells under hypercholesterolemic
      condition. Male rabbits were fed on either normal or high-cholesterol diet for 8
      weeks. Then cholesterol-fed rabbits were randomly assigned to simvastatin or
      starch. At the end of 12 weeks, glomerular mesangial cells were collected. The
      concentrations of TF and PAI-1 mRNA were detected by RT-PCR. The plasma
      activities of TF and PAI-1 were determined with enzyme linked immunosorbent assay
      (ELISA) and chromogenic substrate method, respectively. The atherogenic diet
      caused a consistent increase in serum concentrations of total cholesterol (TC)
      and serum triglyceride (TG) (p < 0.05), increased TF and PAI-1 mRNA expression in
      glomerular mesangial cells and plasma activities as compared to the normal diet
      (p < 0.01). Four-week simvastatin treatment resulted in significant decrease of
      mesangial TF and PAI-1 mRNA (p < 0.01), and also of the plasma activities of TF
      (p < 0.05) and PAI-1 (p < 0.01). These results suggest that simvastatin might
      protect kidney from the formation of microthrombus under hypercholesterolemic
      condition and might be a possible pathogenesis of obesity-related glomerulopathy.

PMID- 16971768
TI  - Influence of prostaglandin A2 on Bax, Bcl-2 and PCNA expression in MCF-7 cells.
AB  - The effects of 20 microg/mL exogenous prostaglandin A(2) (PGA(2)) were determined
      on Bax, Bcl-2 and proliferating cell nuclear antigen (PCNA) expression levels in
      MCF-7 cells. Flow cytometric analysis indicated a pronounced increase in the S
      phase and a decrease in the G(1) phase, whereas a significant increase in the DNA
      content preceding the G(0)/G(1) peak was also observed after 48 h of exposure to
      PGA(2). Confirmation of apoptosis was determined after 12 h, 36 h and 48 h of
      PGA(2) exposure employing the mitosensor reagent that detects potential changes
      in the mitochondrial membrane. Twenty-eight percent of PGA(2)-exposed cells were
      in apoptosis when compared to the 7.1% vehicle-treated cells after 48 h. PGA(2)
      exposure led to statistically significant increase (1.25-fold) over vehicle
      treated controls in Bax expression levels. Decreases in Bcl-2 (0.79-fold), as
      well as PCNA (0.69-fold) expression levels over vehicle-treated controls were
      observed. The Bax/Bcl-2 ratio for PGA(2)-exposed cells was 2.7. The present study
      suggests that an accumulation in the S phase, a decrease in expression levels of
      PCNA, as well as an altered ratio in favor of Bax, could lead to the induction of
      apoptosis in these cells.

PMID- 16971769
TI  - Efficacy of tricyclic antidepressant is associated with beta2-adrenoceptor
      genotype in patients with interstitial cystitis.
AB  - We examined the relationship between the Arg16Gly polymorphism of beta2
      adrenoceptor (ADRB2) and the efficacy of tricyclic antidepressant therapy in
      patients with interstitial cystitis (IC). We studied 55 IC patients and 113
      controls. The IC patients were treated with imipramine hydrochloride, and the
      efficacy of treatment was categorized by patients' satisfaction (no change, fair,
      or good). Genomic DNA was extracted from the controls and IC patients, and the
      Arg16Gly polymorphism of ADRB2 was analyzed. The Arg16Gly polymorphism showed a
      significant difference in prevalence between IC patients and controls, and
      Arg/Arg was associated with increase in the risk of IC than Arg/Gly or Gly/Gly.
      Regarding the tricyclic antidepressant therapy, there was a significant
      difference in the prevalence of this polymorphism between IC patients with no
      change or a fair response to treatment and controls, and Arg/Arg was associated
      with decrease in the response rate to tricyclic antidepressant therapy than
      Arg/Gly or Gly/Gly. Therefore, these results suggest that the Arg16Gly
      polymorphism of ADRB2 is related to down-regulation of ADRB2 expression in the
      detrusor muscle, so that the response of IC to tricyclic antidepressant therapy
      depends on the Arg16Gly polymorphism.

PMID- 16971770
TI  - Exfoliation of the epidermal cells and defecation by amphibian larvae in response
      to coelomic fluid and lysenin from the earthworm Eisenia foetida.
AB  - Coelomic fluid (CF) and lysenin from the earthworm Eisenia foetida induced heavy
      epidermal exfoliation in the larvae of Bufo japonicus formosus at developmental
      stages from hatching (stage 22) to operculum completion (stage 34). In
      experiments with Xenopus laevis, we observed that exfoliated cells were not
      stained by trypan blue. Thus, it appeared that these cells were still alive. It
      is likely, therefore, that both CF and lysenin might disrupt the adhesion between
      epidermal cells of larvae prior to stage 34. Since it is known that lysenin
      exerts its toxic effects through its specific binding to sphingomyelin (SM), SM
      might be involved in such adhesion. This hypothesis was supported by the
      observations that CF and lysenin which had been incubated with SM-liposomes lost
      their exfoliative activity. In larvae after stage 34, the mechanism of adhesion
      between epidermal cells seemed to change and the adhesion was no longer disrupted
      by CF and lysenin. In larvae at around stage 34, a collagen layer started to form
      beneath the basement membrane of the epidermis. Furthermore, larvae at around
      this stage started to eat solid food. The developing collagen layer and food
      intake might be related indirectly to the chemical change in epidermal adhesion.
      The induction of exfoliation by CF and lysenin was also observed in other
      amphibian species. In Bufo larvae, defecation was induced both by CF and by
      lysenin but this effect was independent of exfoliation.

PMID- 16971771
TI  - Reduction of muscle fatigue by catchlike-inducing intermittent electrical
      stimulation in rat skeletal muscle.
AB  - Catchlike property is the force enhancement produced when a brief, high-frequency
      burst of pulses is added to a constant low-frequency stimulation. In functional
      electrical stimulation, constant low-frequency stimulation of approximately 20 Hz
      has primarily been used to reduce muscle fatigue. The purpose of this study was
      to investigate the effects of catchlike-inducing intermittent stimulation on
      muscle fatigue in relation to continuous intermittent low-frequency stimulation.
      Twenty-two adult male Wistar ST rats were randomly assigned into the constant
      frequency stimulation (CFS) group or the catchlike-inducing stimulation (CIS)
      group. In the CFS group, constant low-frequency stimulation of 20 Hz was applied
      intermittently (4 seconds "ON"/15 seconds "OFF"). In the CIS group, a single
      electrical burst of 100 Hz was applied at the start of the every 4-second period
      of stimulation. The muscle fatigue test lasted for 16 min and isometric muscle
      force, muscle fatigue, and muscular workload were evaluated. CIS significantly
      increased the maximum muscular force (under fatigued condition) and workload, and
      significantly decreased muscle fatigue (p < 0.05). The results of this study
      suggest that catchlike-inducing intermittent electrical stimulation is useful in
      the clinical administration of functional electrical stimulation.

PMID- 16971772
TI  - Recombinant human growth hormone (SMP-140) is effective for growth promotion in
      hypophysectomized rats.
AB  - Growth hormone (GH) replacement therapy has been shown to have beneficial effects
      on linear growth enhancement in GH-deficient children over the past few decades.
      SMP-140 is a sterile liquid formation containing rhGH that is expected to improve
      patient compliance and accuracy of dosing, compared with the commercially
      available lyophilized form of GH. However, since there are no data showing that
      SMP-140 influences body elongation in animal models, we studied the effects of
      SMP-140 on body length in hypophysectomized (HPX) rats, which are used as animal
      models of GH deficiency. Consistent with the main feature of GH-deficient
      children, the body length of HPX rats was significantly shorter than that of sham
      operated rats at the start of the study. SMP-140 (0.2, 1 and 5 mg/kg) was
      administered once daily to HPX rats for seven days, and resulted in a dose
      dependent increase in body length and in the width of the growth plate cartilage.
      These results show that SMP-140 administration increases body length in an animal
      model of GH deficiency, and suggest that SMP-140 will be a useful agent for the
      treatment of growth-retarded children.

PMID- 16971773
TI  - Inhibition effect of Oncostatin M on metastatic human lung cancer cells 95-D in
      vitro and on murine melanoma cells B16BL6 in vivo.
AB  - Oncostatin M (OSM) is a multifunctional regulator of cell growth and
      differentiation. It inhibits the growth of many types of tumor cells, but its
      role in metastasis is unknown. We studied the human OSM expressed and purified
      from reconstructed E. Coli on its activity of inhibiting metastasis of tumor
      cells by a series of assays in vitro and in vivo. Clone formation assay in soft
      agar was used to measure the inhibition activity of OSM on the proliferation of
      high metastatic human lung cancer cells 95-D. Cell attachment assay, cell
      migration assay and cell invasion assay were used to evaluate inhibition by OSM
      on 95-D cells of the adhesion ability, the migration ability, and the ability of
      cells to cross tissue barriers, respectively. Inhibition of OSM on secretion of
      MMP-2 and -9 secretion in 95-D cells was determined by Western blot. The in vivo
      inhibitory effect of OSM on metastasis of murine melanoma cells B16BL6 was
      examined in the pulmonary metastasis model. In vitro studies showed that OSM
      inhibited the proliferation of 95-D cells at low concentration. OSM also reduced
      the adhesion and invasion ability of 95-D cells and inhibited the secretion of
      MMP-2 and MMP-9 in OSM treated cells. In vivo results showed that OSM (20
      microg/kg/d for 7 days) inhibited pulmonary metastasis at a rate of 20.7%. There
      were no differences in animal weights among the groups. These results suggest
      that OSM has the potential of being a clinical inhibitor on metastasis of some
      cancer cells.

PMID- 16971774
TI  - [Pharmacogenomics of cardiovascular pharmacology].

PMID- 16971775
TI  - [Diabetes and the metabolic syndrome].

PMID- 16971776
TI  - [Low-molecular-weight HSP and vasopressin in vascular smooth muscle].

PMID- 16971777
TI  - [Intracellular signal transduction of vascular injury in insulin resistance].

PMID- 16971778
TI  - [Role of the Rho/Rho-kinase pathway in the development of hypertensive
      glomerulosclerosis: renoprotective effect of Rho-kinase inhibitor in hypertensive
      glomerulosclerosis and its molecular mechanism].

PMID- 16971779
TI  - [Pleiotropic effects of statins on endothelium and signaling mechanisms].

PMID- 16971780
TI  - [Update on the animal models of schizophrenia].

PMID- 16971781
TI  - [Pharmacological action of antipsychotic drugs].

PMID- 16971782
TI  - [PET (positron emission tomography) research on schizophrenia].

PMID- 16971783
TI  - Geographical variation in echolocation call and body size of the Okinawan least
      horseshoe bat, Rhinolophus pumilus (Mammalia: Rhinolophidae), on Okinawa-jima
      Island, Ryukyu Archipelago, Japan.
AB  - The Okinawan least horseshoe bat, Rhinolophus pumilus, is a cave-dwelling species
      endemic to the central and southern Ryukyus, Japan. We analyzed variation in the
      constant frequency (CF) of the echolocation call and in forearm length (FAL) of
      this species on Okinawa-jima Island on the basis of data for 479 individuals from
      11 caves scattered over the island. CF values in samples from six caves, all
      located in the southwestern half of Okinawa-jima, were significantly higher than
      those in samples from five caves in the northeastern half of the island. Also,
      FAL was significantly greater in the latter group than in the former group,
      although the ranges of variation in this character substantially overlapped
      between the two groups. These results suggest substantial differentiation between
      R. pumilus populations on Okinawa-jima. The implications of our findings for the
      conservation of this endangered bat species are briefly discussed.

PMID- 16971784
TI  - Vertical transmission of photosymbionts in the colonial ascidian Didemnum molle:
      the larval tunic prevents symbionts from attaching to the anterior part of
      larvae.
AB  - Morphological processes in the vertical transmission of photosymbionts were
      investigated in the Prochloron-bearing ascidian Didemnum molle. Prochloron cells
      were found exclusively in the common cloacal cavity of the colony, attached
      mainly to the tunic lining of the cavity wall. Oocytes were found in the
      abdominal region of each zooid, but no Prochloron cells were associated with this
      stage. During embryogenesis, embryos moved into the tunic core of the colony and
      were always separated from Prochloron cells in the cloacal cavity by the tunic
      matrix, until they hatched out from the tunic core. In swimming larvae,
      Prochloron cells covered the surface of the posterior half of the larval trunk,
      whereas a thin larval tunic layer covered the anterior half, where no Prochloron
      cells were found. The tunic of the posterior half of the larval trunk had many
      folds that enfolded the Prochloron cells and may be adhesive in order to acquire
      Prochloron cells from the mother colony. The thin larval tunic layer is probably
      not adhesive and protects the anterior half of the trunk from interference by
      Prochloron cells with sensory receptors and adhesive organs.

PMID- 16971785
TI  - Molecular cloning of cDNA encoding APC11, a catalytic component of anaphase
      promoting-complex (APC/C), from goldfish (Carassius auratus), and establishment
      of in vitro ubiquitinating system.
AB  - Destruction of cyclin B is required for exit from mitosis and meiosis. A cyclin
      degrading system, including anaphase-promoting-complex/cyclosome (APC/C), has
      been shown to be responsible for cyclin B destruction. Here we present the
      cloning, sequencing, and expression analysis of goldfish (Carassius auratus)
      APC11, which encodes the catalytic component of APC/C from goldfish ovary. The
      cloned cDNA is 348 bp long and encodes 88 amino acids. The deduced amino acid
      sequence is highly homologous to APC11 from other species. The expression of mRNA
      for APC11 was ubiquitous among tissues, as opposed to that of mRNA for E2-C,
      which occurred at a very high level in the ovary. Recombinant goldfish APC11
      possesses ubiquitinating activity against cyclin B. We established an in vitro
      ubiquitinating system of proteins composed of purified recombinant E1, E2-C, and
      APC11 from goldfish. The reconstructed system for these ubiquitinating enzymes
      makes it feasible to elucidate the molecular mechanism of cyclin B degradation.

PMID- 16971786
TI  - Association of a 66 kDa homolog of Chlamydomonas DC2, a subunit of the outer arm
      docking complex, with outer arm dynein of sperm flagella in the ascidian Ciona
      intestinalis.
AB  - We previously identified a 66 kDa axonemal protein (Ci-Axp66.0) in sperm of the
      ascidian Ciona intestinalis. Here we found that Ci-Axp66.0 shows sequence
      similarity to the DC2 subunit of the Chlamydomonas outer arm docking complex.
      Analysis of secondary structure of Ci-Axp66.0 suggested that the N-terminal two
      thirds of the molecule is rich in coiled coil structure, as in Chlamydomonas DC2.
      Immunogold localization revealed that it is located in the vicinity of outer arm
      dynein. Ci-Axp66.0 was partly extracted from the axonemes by a high salt solution
      and co-purified with outer arm dynein. This co-purification was not affected by
      the absence of Mg(2+) in isolation buffer, indicating that Ci-Axp66.0 is
      associated with outer arm dynein. These results suggest that Ci-Axp66.0 is a
      component of the outer arm dynein docking complex in the axonemes of Ciona sperm.

PMID- 16971787
TI  - Ledgerline, a novel Xenopus laevis gene, regulates differentiation of presomitic
      mesoderm during somitogenesis.
AB  - Segmentation of the vertebrate body via the sequential formation of somites is an
      important process in embryogenesis. This sequential process is governed by the
      activation and regulation of Notch-related molecular oscillators by fibroblast
      growth factor and retinoic acid (RA) signaling. In this study, we identified
      ledgerline, a novel gene of Xenopus laevis expressed specifically in the
      presomitic mesoderm. Knockdown of ledgerline using antisense morpholino
      oligonucleotides shifted the developing somite front and altered the expression
      of genes that regulate molecular oscillation, including Delta2, ESR5, Hairy2a,
      and Thylacine1. Knockdown of ledgerline also downregulated RALDH-2 expression.
      Injection of RARalpha-CA, a constitutively active mutant of the RA receptor
      RARalpha, subsequently reduced the altered Thylacine1 expression. These results
      strongly suggest that ledgerline is essential for mesodermal RA activity and
      differentiation of the presomitic mesoderm during Xenopus somitogenesis.

PMID- 16971788
TI  - A gastric-brooding asteroid, Smilasterias multipara.
AB  - The gastric-brooding asterinid sea star, Smilasterias multipara, broods from late
      August to early November in the shallow sublittoral zone of southeastern
      Australia. We observed males and females spawning in the laboratory. They shed
      gametes through gonopores on the sides of the arms. The eggs were orange, about
      1.0 mm in diameter, and heavier than seawater. They were externally fertilized by
      sperm, and placed into the stomach of the female by the tube feet. Twenty-four
      hours after fertilization, the first cleavage occurred. Cleavage was equal,
      total, and radial. Development via a non-feeding lecithotrophic brachiolaria was
      direct, there being no planktrotrophic bipinnaria or brachiolaria larva. Embryos
      developed, through wrinkled blastula and gastrula stages, into brachiolariae with
      arms. All of the surfaces of the brachiolaria were covered by cilia. At
      metamorphosis, a starfish rudiment appeared on the posterior portion of the
      larval body, while the anterior portion of the larval body was absorbed. Two
      months after fertilization, metamorphosis was complete. After metamorphosis,
      juveniles in the stomach grew six pairs of tube feet in each arm. Juveniles, 3 mm
      in diameter, emerged from the mouth of the mother in early November.
      Developmental evidence suggests that this asteroid has evolved mechanisms for the
      protection of larvae and juveniles from gastric digestion.

PMID- 16971789
TI  - Effects of acid water exposure on plasma cortisol, ion balance, and immune
      functions in the "cobalt" variant of rainbow trout.
AB  - This study was undertaken to examine physiological responses to acidification of
      environmental water in the "cobalt" variant of rainbow trout (Oncorhynchus
      mykiss), which exhibits malformation of the pituitary, by following changes in
      plasma levels of cortisol and electrolytes, blood pH, gill Na(+), K(+)-ATPase
      activity, and immune functions after exposure to acid water (pH 4.5). Resting
      levels of plasma cortisol and lysozyme were significantly lower in the cobalt
      variant than in the normal trout, whereas plasma ceruloplasmin was significantly
      higher in the cobalt variant, suggesting that some endocrine factors, lacking or
      deficient in the cobalt variant, are important for the regulation of its immune
      functions. Blood pH was slightly but significantly lower in the cobalt variant at
      rest. After exposure to acid water for 24 h, both the normal trout and cobalt
      variant showed a significant elevation in plasma cortisol, although the increased
      level in the cobalt variant was still lower than that in the normal trout
      transferred to neutral water. No differences were seen in blood pH, plasma
      electrolytes, and gill Na(+), K(+)-ATPase activity between the normal trout and
      the cobalt variant, indicating that the cobalt variant regulates ion balance when
      exposed to acid water, despite malformation of the pituitary. Although the normal
      trout showed a reduction in plasma lysozyme level after acid exposure, there was
      no significant change in the cobalt trout. Adverse effects of pituitary
      malformation on ion balance and immune functions may be compensated by
      extrapituitary factors in the cobalt variant when it is exposed to acid water.

PMID- 16971790
TI  - A rapid increase in cAMP in response to 20-hydroxyecdysone in the anterior silk
      glands of the silkworm, Bombyx mori.
AB  - In the anterior silk glands (ASGs) of the silkworm, Bombyx mori, intracellular
      cAMP increases transiently to a very high level shortly after the hemolymph
      ecdysteroid peak in the prepupal period. In cultured ASGs obtained on the day of
      gut-purge, cAMP levels were increased by 20-hydroxyecdysone (20E), and this
      increase was enhanced by an inhibitor of phosphodiesterase, but was not affected
      by alpha-amanitin, indicating the 20E action may not be mediated via gene
      expression. The increase in cAMP occurred within 30 seconds of exposure to a
      physiological concentration of 20E (1 microM), and also by ponasterone A. Our
      findings indicate a nongenomic action of ecdysteroids in insects, which may be an
      additional mechanism by which this steroid hormone induces acute responses in
      tissues and cells.

PMID- 16971791
TI  - Calves born from anestrus yaks (Poephagus grunniens L.) subjected to Ovsynch and
      superovulation treatment.
AB  - An attempt was made to induce estrus and ovulation in eight anestrus yaks by use
      of the Ovsynch protocol. Six out of eight yaks were successfully induced into
      estrus, and ovulation occurred in all the responding yaks 1-2 days after the
      second GnRH administration. Out of the six animals that responded to the
      treatment, two mated naturally with yak bulls, and calves were obtained from
      them. The other four animals were further administered a superovulatory regimen
      of Folltropin (FSH-P). Following Folltropin and Ilerin (a PGF(2alpha) analog)
      treatment, the animals were subjected to natural insemination. Only one animal in
      which natural mating occurred was flushed non-surgically for embryo recovery 7
      days post-insemination. Thereafter, all the donor animals were administered with
      Ilerin. After 48-72 h, they came into heat and mated naturally with yak bulls,
      and calves were obtained from them after expiration of the normal gestation
      period. Following superovulation, the average numbers of palpable corpora lutea
      in the right and left ovaries were 2.25+/-0.6 and 1.75 +/-0.3, respectively.
      Three embryos were recovered by non-surgical flushing from a single animal. One
      embryo was transferred to a recipient yak, who produced one female calf after 258
      days. This is the first report of production of a yak calf through embryo
      transfer-technology.

PMID- 16971792
TI  - A new species of Amolops from Thailand (Amphibia, Anura, Ranidae).
AB  - We describe a new species of torrent-dwelling ranid frog of the genus Amolops
      from western to peninsular Thailand. Amolops panhai, new species, differs from
      its congeners by the combination of: small body, males 31-34 mm, females 48-58 mm
      in snout-vent length; head narrower than long; tympanum distinct; vomerine teeth
      in short, oblique patches; first finger subequal to second; disc of first finger
      smaller than that of second, with circummarginal groove; no wide fringe of skin
      on third finger; toes fully webbed; outer metatarsal tubercle present;
      supratympanic fold present; dorsolateral fold indistinct; axillary gland present;
      horny spines on back, side of head and body, and chest absent; large tubercles on
      side of anus absent; glandular fold on ventral surface of tarsus absent; nuptial
      pad and paired gular pouches present in male; white band along the upper jaw
      extending to shoulder absent; larval dental formula 7(4-7)/3(1). This new species
      is the second anuran discovered which has a disjunct distribution around the
      Isthmus of Kra.

PMID- 16971793
TI  - A new species of Osedax (Annelida: Siboglinidae) associated with whale carcasses
      off Kyushu, Japan.
AB  - A new whale-bone-eating polychaete species of the genus Osedax was found on sperm
      whale carcasses submerged off Cape Nomamisaki, Kyushu, Japan, at a depth of
      approximately 200 m. The new species, Osedax japonicus, is the fourth known
      species of the genus Osedax and the first species from the western Pacific.
      Female O. japonicus specimens (1) form dense clusters on whale carcasses; (2)
      have a body composed of crown, trunk, and root structure; (3) lack a digestive
      tract; and (4) have bacterium-like particles in the tissue of the root structure.
      Osedax japonicus shares all these characteristics with O. rubiplumus and O.
      frankpressi, and items (1) to (3) with O. mucofloris. Osedax japonicus is easily
      distinguished from the other three known species by oviduct morphology, body
      length, and palp coloration in females. No males of O. japonicus have yet been
      found.

PMID- 16971794
TI  - Navigation-based needle puncture of a cadaver using a hybrid tracking
      navigational system.
AB  - PURPOSE: The purpose of this study was to determine the puncture accuracy of a
      navigational system, Medarpa, in a soft tissue environment using augmented
      overlay imaging. MATERIALS AND METHODS: Medarpa is an optical electromagnetic
      tracking system, which allows tracking of instruments, the radiologist's head
      position, and the transparent display. The display superimposes a computed
      tomography scan of a cadaver chest on a human cadaver in real time. In group A,
      needle puncture was performed using the Medarpa system. Three targets located
      inside the cadaver chest were selected. In group B, the same targets were used to
      perform standard computed tomography-guided puncture using a single-slice
      technique. A total of 42 punctures were performed in each group. Postpuncture
      computed tomography scans were made to verify needle tip positions. RESULTS: Mean
      deviation from targets was 8.42 mm +/- 1.78 mm for group A and 8.90 mm +/- 1.71
      mm for group B. No significant difference was found between group A and B in any
      target (P > 0.05). No significant difference was found between the targets of the
      same group (P > 0.05). Procedural time for 42 punctures was 160 minutes in group
      A versus 289 minutes in group B (P < 0.05). CONCLUSION: Needle puncture in a soft
      tissue environment using the navigational system Medarpa can be reliably
      performed and matches the accuracy achieved by a computed tomography-guided
      puncture technique.

PMID- 16971795
TI  - Effect of microbubble ligation to cells on ultrasound signal enhancement:
      implications for targeted imaging.
AB  - OBJECTIVES: Molecular imaging with contrast-enhanced ultrasound (CEU) relies on
      the detection of microbubbles retained in regions of disease. The aim of this
      study was to determine whether microbubble attachment to cells influences their
      acoustic signal generation and stability. MATERIALS AND METHODS: Biotinylated
      microbubbles were attached to streptavidin-coated plates to derive density versus
      intensity relations during low- and high-power imaging. To assess damping from
      microbubble attachment to solid or cell surfaces, in vitro imaging was performed
      for microbubbles charge-coupled to methacrylate spheres and for vascular cell
      adhesion molecule-1-targeted microbubbles attached to endothelial cells. RESULTS:
      Signal enhancement on plates increased according to acoustic power and
      microbubble site density up to 300 mm. Microbubble signal was reduced by
      attachment to solid spheres during high- and low-power imaging but was minimally
      reduced by attachment to endothelial cells and only at low power. CONCLUSION:
      Attachment of targeted microbubbles to rigid surfaces results in damping and a
      reduction of their acoustic signal, which is not seen when microbubbles are
      attached to cells. A reliable concentration versus intensity relationship can be
      expected from microbubble attachment to 2-dimensional surfaces until a very high
      site density is reached.

PMID- 16971796
TI  - Evaluation of a newly developed percutaneous thrombectomy basket device in sheep
      with central pulmonary embolisms.
AB  - OBJECTIVE: The authors studied the development of a thrombectomy device that is
      adequately steerable and quickly placeable in case of extensive pulmonary
      embolism. MATERIALS AND METHODS: The device consists of a self-expandable nitinol
      basket mounted at a catheter-tip, which allows suction and extraction of thrombus
      material. Five in vitro tests were performed followed by tests in 6 sheep. In
      vivo thrombus material was introduced through a jugular vein to produce pulmonary
      embolism. After catheter insertion over the right femoral vein, the basket was
      placed adjacent to the pulmonary embolus and the extraction procedure was
      performed. RESULTS: In in vitro tests, the extracted thrombus amount varied
      between 60% and 95%. In animal experiments, the extracted amount varied between
      30% and 95% as determined angiographically. Limiting factors were steerability
      and optimal positioning of the basket in relation to the embolus. CONCLUSIONS:
      Extraction of pulmonary embolism with the self-expanding suction basket is
      feasible. However, successful recanalization is limited by catheter
      maneuverability in the pulmonary arterial system.

PMID- 16971797
TI  - Evaluation of pulmonary function using breathing chest radiography with a dynamic
      flat panel detector: primary results in pulmonary diseases.
AB  - OBJECTIVES: Dynamic flat panel detectors (FPD) permit acquisition of distortion
      free radiographs with a large field of view and high image quality. The present
      study was performed to evaluate pulmonary function using breathing chest
      radiography with a dynamic FPD. We report primary results of a clinical study and
      computer algorithm for quantifying and visualizing relative local pulmonary
      airflow. MATERIALS AND METHODS: Dynamic chest radiographs of 18 subjects (1
      emphysema, 2 asthma, 4 interstitial pneumonia, 1 pulmonary nodule, and 10 normal
      controls) were obtained during respiration using an FPD system. We measured
      respiratory changes in distance from the lung apex to the diaphragm (DLD) and
      pixel values in each lung area. Subsequently, the interframe differences (D
      frame) and difference values between maximum inspiratory and expiratory phases (D
      max) were calculated. D-max in each lung represents relative vital capacity (VC)
      and regional D-frames represent pulmonary airflow in each local area. D-frames
      were superimposed on dynamic chest radiographs in the form of color display
      (fusion images). The results obtained using our methods were compared with
      findings on computed tomography (CT) images and pulmonary functional test (PFT),
      which were examined before inclusion in the study. RESULTS: In normal subjects,
      the D-frames were distributed symmetrically in both lungs throughout all
      respiratory phases. However, subjects with pulmonary diseases showed D-frame
      distribution patterns that differed from the normal pattern. In subjects with air
      trapping, there were some areas with D-frames near zero indicated as colorless
      areas on fusion images. These areas also corresponded to the areas showing air
      trapping on computed tomography images. In asthma, obstructive abnormality was
      indicated by areas continuously showing D-frame near zero in the upper lung.
      Patients with interstitial pneumonia commonly showed fusion images with an uneven
      color distribution accompanied by increased D-frames in the area identified as
      normal on computed tomography images. Furthermore, measurement of DLD was very
      effective for evaluating diaphragmatic kinetics. CONCLUSIONS: This is a rapid and
      simple method for evaluation of respiratory kinetics for pulmonary diseases,
      which can reveal abnormalities in diaphragmatic kinetics and regional lung
      ventilation. Furthermore, quantification and visualization of respiratory
      kinetics is useful as an aid in interpreting dynamic chest radiographs.

PMID- 16971798
TI  - Thick maximum intensity projections for the assessment of left ventricular
      function with 64-slice computed tomography.
AB  - OBJECTIVE: The objective of this study was to assess the accuracy of thick
      maximum intensity projections (MIP) from computed tomography (CT) data sets
      mimicking projection images from biplane ventriculography for evaluation of left
      ventricular (LV) parameters. MATERIALS AND METHODS: Fifty-eight patients
      underwent 64-slice CT. Multiphase images were reconstructed in 10% steps of the
      RR interval. MIP images (70-mm thickness) of the contrast-enhanced LV in fixed 30
      degrees right anterior oblique (RAO)/60 degrees left anterior oblique (LAO) and
      in adapted short-/long-axis planes were reconstructed. LV parameters were
      calculated using the area-length method formula. Three-dimensional assessment
      with semiautomated software served as reference standard. RESULTS: Use of thick
      MIP reconstructions had a high intermethod reliability (86-94%) compared with the
      3-dimensional approach. Smaller measurement errors were found for thick MIP
      reconstructions in adapted short-/long-axis planes. A significant projection
      error (3.0%, P < 0.001) of thick MIP reconstructions was found using fixed 30
      degrees RAO/60 degrees LAO compared with adapted short-/long-axis
      reconstructions. CONCLUSION: Thick MIP reconstructions with adapted short-/long
      axis planes allow an accurate assessment of LV parameters compared with the
      established 3-dimensional method.

PMID- 16971799
TI  - Shape-constraint region growing for delineation of hepatic metastases on contrast
      enhanced computed tomograph scans.
AB  - OBJECTIVES: The objectives of this study were to develop a shape-constraint
      region-growing algorithm to automatically delineate liver metastases on computed
      tomography images and to compare automated tumor measurements with those outlined
      manually by radiologists. METHODS: The algorithm starts with a manual selection
      of a seed lesion region of interest (ROI). Based on intensity distributions of
      the seed ROI and the liver parenchyma, several parameters are computed and used
      to adaptively guide the region growing. To prevent the region growing from
      leaking into surrounding tissues of similar characteristics, specific shape
      constraints, including a local shape, a global shape, and a gravity-shift index,
      are developed to jointly control the iteration of the region growing. The
      algorithm was applied to 59 lesions in 14 patients with liver metastases. The
      maximal diameter (unidimension), the product of the maximal and maximal
      perpendicular diameters (bidimension), and the area in the axial plane were
      calculated for each of the segmented lesions. Three independent radiologists
      manually measured all the lesions once, and one of the radiologists measured each
      lesion 3 times. For each measurement, the concordance correlation coefficient
      (CCC) was used to assess the pairwise agreement between the computer and the
      different radiologists, and the overall concordance correlation coefficient
      (OCCC) was used to assess the agreement between the computer and the multiple
      radiologists and between the one radiologist's 3 readings. RESULTS: Fifty-three
      of 59 (89.8%) lesions in 14 patients with liver metastases were successfully
      segmented using this algorithm. The algorithm achieved a median accuracy of
      88.0%. CCCs/OCCCs ranged from 0.943 to 0.999 with 95% confidence intervals.
      CONCLUSIONS: High accuracy and CCCs/OCCCs suggested that measurements made by the
      computer were very similar to those made by the radiologists.

PMID- 16971800
TI  - Three-dimensional cerebral contrast-enhanced magnetic resonance venography at 3.0
      Tesla: initial results using highly accelerated parallel acquisition.
AB  - OBJECTIVE: The objective of this study was to evaluate a high spatial resolution
      3-dimensional (3D) contrast-enhanced magnetic resonance (CE-MR) venography
      protocol for evaluation of intracranial venous system using highly accelerated
      parallel imaging at 3.0 T. MATERIALS AND METHODS: Ten patients (4 male, 6 female;
      age, 38-76 years) with suspected cerebrovascular disease were prospectively
      studied on a 32-channel 3.0 T MR system. After a single intravenous contrast
      injection, high spatial resolution 3D CE-MR angiography of the entire supraaortic
      arteries was performed followed immediately by 3D cerebral CE-MR venography. By
      using a fast 3D gradient-recalled-echo sequence with elliptic centric k-space
      ordering and highly accelerated parallel acquisition (acceleration factor 3 and 2
      in phase and slice encoding direction, respectively), 3D cerebral CE-MR
      venography was acquired with voxel dimensions of 0.7 x 0.7 x 0.8 mm in 24
      seconds. Image evaluation was performed independently by 2 neuroradiologists for
      overall image quality, presence of noise, and artifacts. The image quality of 30
      venous segments was evaluated in each subject using a 1 to 4 scoring scale. In 2
      patients, catheter angiography was available for correlation. Statistical
      analysis of data was performed by using Wilcoxon rank sum test and kappa
      coefficient. RESULTS: All studies were determined to be of diagnostic image
      quality by both observers. The majority (90%) of cerebral venous segments were
      evaluated to be of diagnostic image quality (median, 3; range, 3-4) by both
      readers and with excellent interobserver agreement (kappa = 0.86; 95% confidence
      interval, 0.79-0.93). One meningioma invading the superior sagittal sinus and one
      superior sagittal sinus fistula were detected subsequently confirmed by
      conventional angiography. CONCLUSION: High spatial resolution 3D cerebral CE-MR
      venography is feasible and promising. Using a 32-channel 3.0 T system combined
      with multichannel array coils effectively supports highly accelerated parallel
      imaging, enabling subsequent acquisition of both high spatial resolution CE-MR
      angiography and CE-MR venography after a single contrast injection without
      impairing the image quality. More extensive clinical studies are warranted to
      establish the range of applications and confirm the accuracy of this technique.

PMID- 16971801
TI  - Multishot diffusion-weighted PROPELLER magnetic resonance imaging of the abdomen.
AB  - OBJECTIVE: The objective of this study was to evaluate the feasibility of using
      multishot PROPELLER for diffusion-weighted imaging (DWI) of the abdomen.
      MATERIALS AND METHODS: Diffusion-weighted abdominal imaging was performed in 9
      healthy volunteers and 3 patients using both single-shot DW-SE-EPI and multishot
      DW-PROPELLER (BLADE sequence). We compared ADC measurements in phantoms, liver
      and pancreatic tissues and performed qualitative comparisons of the diffusion
      weighted images and ADC maps provided by these 2 techniques. RESULTS: DW
      PROPELLER significantly improved image quality (P < 0.05) with reduced geometric
      distortion and artifact. The ADC values of phantoms and abdominal organs measured
      by DW-PROPELLER were generally greater than those measured by single-shot DW-SE
      EPI. The ADC values measured by both DWI techniques were significantly different
      for liver tissues but not for pancreatic tissues (P < 0.05). Preliminary patient
      studies demonstrated clearly distinguished lesion areas from surrounding normal
      liver tissues in the DW-PROPELLER images. DW-PROPELLER offers the potential for
      high-resolution DWI of the abdomen. CONCLUSIONS: The multishot DW-PROPELLER
      sequence is a promising technique for DWI of abdominal organs. Future clinical
      studies will evaluate the use of DW-PROPELLER technique for abdominal oncologic
      imaging applications.

PMID- 16971802
TI  - Tolerogenic dendritic cells: the ins and outs of outcome.
AB  - Recent studies point to an important role for dendritic cells (DCs) in the
      induction of peripheral tolerance, revealing that the maturation and/or
      activation state of DCs might be a control point for the induction of peripheral
      tolerance. Recent progress in our understanding of the mechanisms mediating
      immune tolerance indicates them to be far more complex than hitherto anticipated.
      Factors deciding the outcome of vaccination with autologous DCs to prevent and
      treat diseases with an autoimmune background include maturation state of DCs,
      their administration route, long-term effects, antigen loading, and in vivo
      microenvironment. DC vaccination, although promising, is far from standardized.
      In this review, we discuss the ins and outs of DC-mediated immune tolerance and
      the need for careful experimental design to unequivocally prove the efficacy and
      reach the goal of optimized use of DCs in autoimmune diseases.

PMID- 16971803
TI  - Manufacturing and quality control of cell-based tumor vaccines: a scientific and
      a regulatory perspective.
AB  - Tumor vaccines play an increasingly important role in the therapy of various
      malignant diseases. The efficacy of these new products is currently being
      explored in many clinical trials all over the world. Cell-based tumor vaccines
      can be classified as somatic cell therapy, or, depending on whether genetic
      modifications have been applied, as gene-transfer medicinal products. Few
      specific guidance documents are available to standardize the development and
      production of cell-based tumor vaccines. Here, we review the different types of
      cell-based cancer vaccines that are currently being used in clinical trials.
      Furthermore, we discuss regulatory guidance documents available in the European
      Union and describe methods that have been applied so far to ensure that the cell
      based vaccines meet acceptable standards, including potency assays.

PMID- 16971804
TI  - Antitumor activity of a dual cytokine/single-chain antibody fusion protein for
      simultaneous delivery of GM-CSF and IL-2 to Ep-CAM expressing tumor cells.
AB  - Cytokine targeting to tumor-associated antigens via antibody cytokine fusion
      proteins has demonstrated potent antitumor activity in numerous animal models and
      has led to the clinical development of 2 antibody-interleukin-2 (IL-2) fusion
      proteins. We previously reported on the construction and in vitro properties of a
      "dual" cytokine fusion protein for simultaneous targeted delivery of human
      granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-2 to human
      tumors. The fusion protein is based on a heterodimerized core structure formed by
      human CH1 and Ckappa domains (heterominibody) with C-terminally fused human
      cytokines and N-terminally fused single-chain antibody fragments specific for the
      tumor-associated surface antigen epithelial cell adhesion molecule (Ep-CAM). For
      testing the antitumor activity in syngeneic mouse xenograft models, we developed
      "dual cytokine heterominibodies" with murine cytokines (mDCH). mDCH fusion
      proteins and, as controls, "single cytokine heterominibodies" (SCH) carrying
      either murine GM-CSF (mGM-CSF) or murine IL-2 (mIL-2) were constructed, of which
      all retained the specific activities of cytokines and binding to the Ep-CAM
      antigen on human Ep-CAM transfected mouse colon carcinoma CT26-KSA cells. Over a
      5-day treatment course, DCH fusion proteins induced significant inhibition of
      established pulmonary CT26-KSA metastases in immune-competent Balb/c mice at low
      daily doses of 1 mug of fusion protein per mouse. However, with the tested dosing
      schemes, antitumor activity of mDCH was largely independent of cytokine targeting
      to tumors as demonstrated by a control protein with mutated Ep-CAM binding sites.
      Single cytokine fusion proteins mSCH-GM-CSF and mSCH-IL-2 showed similar
      antitumor activity as the dual cytokine fusion protein mDCH, indicating that GM
      CSF and IL-2 in one molecule did not significantly synergize in tumor rejection
      under our experimental conditions. Our results seem to contradict the notion that
      IL-2 and GM-CSF can synergize in antitumor activity and that with conventional
      dose regimens, their specific targeting to tumors, as tested here with 2
      antibodies of different affinities, enhances their antitumor activity.

PMID- 16971805
TI  - The Fc portion of UV3, an anti-CD54 monoclonal antibody, is critical for its
      antitumor activity in SCID mice with human multiple myeloma or lymphoma cell
      lines.
AB  - UV3 is a monoclonal antibody that recognizes human CD54 (intercellular adhesion
      molecule-1), and it was generated for the therapy of human multiple myeloma. In a
      severe combined immunodeficient (SCID) xenograft model of human multiple myeloma,
      UV3 significantly prolonged the survival of mice with either early or advanced
      stages of disease. However, the mechanism by which UV3 exerted its antitumor
      effect remained unknown. As reported previously UV3 could mediate antibody
      dependent cell-mediated cytotoxicity or complement-dependent cytotoxicity in
      vitro. F(ab)'2 fragments of UV3 had therapeutic efficacy in vivo, suggesting that
      effector functions were not critical. The purpose of this study was to further
      define the importance of the Fc portion of UV3 for its antitumor activity in
      vivo. To this end, we examined the effect of an "ultrapure" preparation of UV3
      F(ab)'2 to treat SCID mice xenografted with either ARH-77 cells, a human multiple
      myeloma cell line, or Daudi cells, a human Burkitt's lymphoma cell line. In
      addition, we evaluated different doses of UV3 immunoglobulin G (IgG) in these
      mice to determine the minimum amount of IgG that would produce a therapeutic
      effect. Data obtained from this study suggest that (1) the Fc portion of UV3 is
      critical for its antitumor activity in vivo, (2) low levels of UV3 IgG in a
      preparation of F(ab)'2 fragments account for all of its in vivo activity in
      multiple myeloma and most of its activity in lymphoma, and (3) UV3 IgG
      significantly prolongs the survival of SCID/ARH-77 mice as well as SCID/Daudi
      mice.

PMID- 16971806
TI  - Blood dendritic cells generated with Flt3 ligand and CD40 ligand prime CD8+ T
      cells efficiently in cancer patients.
AB  - Flt3 ligand mobilizes dendritic cells (DCs) into blood, allowing generation in
      vivo of large numbers of DCs for immunotherapy. These immature DCs can be rapidly
      activated by soluble CD40 ligand (CD40L). We developed a novel overnight method
      using these cytokines to produce DCs for cancer immunotherapy. Flt3 ligand
      mobilized DCs (FLDCs) were isolated, activated with CD40L, loaded with antigenic
      peptides from influenza matrix protein, hepatitis B core antigen, NY-ESO-1, MAGE
      A4, and MAGE-A10, and injected into patients with resected melanoma. Three
      injections were given at 4-week intervals. Study end points included antigen
      specific immune responses (skin reactions to peptides alone or peptide-pulsed
      FLDCs; circulating T-cell responses), safety, and toxicity. No patient had a
      measurable tumor. Six patients were entered. FLDCs were obtained, enriched, and
      cultured under Good Manufacturing Practice grade conditions. Overnight culture
      with soluble CD40L caused marked up-regulation of activation markers (CD83 and
      HLA-DR). These FLDCs were functional and able to stimulate antigen-specific T
      cells in vitro. No significant adverse events were attributable to FLDCs. Peptide
      pulsed FLDCs caused strong local skin reactions up to 60 mm diameter with intense
      perivascular infiltration of T cells, exceeding those seen in our previous
      peptide-based protocols. Antigen-specific blood T-cell responses were induced,
      including responses to an antigen for which the patients were naive (hepatitis B
      core antigen) and MAGE-A10. MAGE-A10-specific T cells with a skewed T-cell
      receptor repertoire were detected in 1 patient in blood ex vivo and from tumor
      biopsies. Vaccination with FLDCs pulsed with peptides is safe and primes immune
      responses to cancer antigens.

PMID- 16971807
TI  - Simultaneous activation of viral antigen-specific memory CD4+ and CD8+ T-cells
      using mRNA-electroporated CD40-activated autologous B-cells.
AB  - Recently, it has become obvious that not only CD8 T-cells, but also CD4 T-helper
      cells are required for the induction of an effective, long-lasting cellular
      immune response. In view of the clinical importance of cytomegalovirus (CMV) and
      human immunodeficiency virus (HIV) infection, we developed 2 strategies to
      simultaneously reactivate viral antigen-specific memory CD4 and CD8 T-cells of
      CMV-seropositive and HIV-seropositive subjects using mRNA-electroporated
      autologous CD40-activated B cells. In the setting of HIV, we provide evidence
      that CD40-activated B cells can be cultured from HAART-naive HIV-1 seropositive
      patients. These cells not only express and secrete the HIV p24 antigen after
      electroporation with codon-optimized HIV-1 gag mRNA, but can also be used to in
      vitro reactivate Gag antigen-specific interferon-gamma-producing CD4 and CD8
      autologous T-cells. For the CMV-specific approach, we applied mRNA coding for the
      pp65 protein coupled to the lysosomal-associated membrane protein-1 to transfect
      CD40-activated B cells to induce CMV antigen-specific CD4 and CD8 T-cells. More
      detailed analysis of the activated interferon-gamma-producing CMV pp65 tetramer
      positive CD8 T-cells revealed an effector memory phenotype with the capacity to
      produce interleukin-2. Our findings clearly show that the concomitant activation
      of both CD4 and CD8 (memory) T-cells using mRNA-electroporated CD40-B cells is
      feasible in CMV and HIV-1-seropositive persons, which indicates the potential
      value of this approach for application in cellular immunotherapy of infectious
      diseases.

PMID- 16971808
TI  - ReGel polymer-based delivery of interleukin-2 as a cancer treatment.
AB  - ReGel is an aqueous, filter sterilizable ABA tri-block polymer consisting of poly
      (lactide-co-glycolide) and polyethylene glycol. We tested the suitability of this
      polymer to provide sustained interleukin-2 (IL-2) delivery for cancer
      immunotherapy. ReGel/IL-2 is liquid at or below room temperature, and is easily
      injectable through narrow gauge needles, but undergoes a reversible thermal
      transition into a bioerodible depot at body temperature. We demonstrated that
      ReGel/IL-2 releases IL-2 over 72 to 96 hours in vitro, without loss of
      bioactivity. Pharmacokinetic studies after peritumoral injection of 0.1 mL
      ReGel/IL-2 in mice demonstrated an early burst of IL-2 release, followed by more
      sustained release kinetics over 96 hours (T(1/2)beta 48 h). Less than 1.5% of the
      injected dose was detectable in blood or kidneys during the first 48 hours. A
      single peritumoral dose of ReGel/IL-2 [1 to 4 million international units (MIU)
      ReGel/IL-2, split into 4 quadrant injections] was administered to mice bearing
      subcutaneous RD-995 spindle cell carcinoma. Only the highest dose of ReGel/IL-2
      tested (4.0 MIU) resulted in significant hypotension on day 3 after injection.
      Weekly treatment of Meth A fibrosarcoma and RENCA renal carcinoma with ReGel/IL-2
      (2 MIU/dose) induced a significant reduction in tumor growth and improved
      survival. Reduction in tumor growth at implants remote from treated lesions was
      also observed, suggesting systemic activation of antitumor immunity. These
      findings establish that peritumoral injection of ReGel/IL-2 is an effective
      delivery system for cancer immunotherapy, while decreasing IL-2 toxicity. This
      polymer delivery system is likely to be broadly applicable for sustained delivery
      of other cytokines and peptides.

PMID- 16971809
TI  - Rituximab but not other anti-CD20 antibodies reverses multidrug resistance in 2 B
      lymphoma cell lines, blocks the activity of P-glycoprotein (P-gp), and induces P
      gp to translocate out of lipid rafts.
AB  - The objective of this study was to investigate the ability of the anti-CD20
      antibody, Rituximab (RTX), to inhibit the activity of P-glycoprotein (P-gp), and
      reverse multidrug resistance (MDR) in 2 P-gp/CD20 lymphoma cell lines. We
      determined whether RTX would chemosensitize the 2 P-gp cell lines in vitro, and
      inhibit the ability of the cells to efflux Rhodamine 123. One cell line was
      infected with an MDR1 vector and the other was generated by drug selection. We
      also determined whether RTX induced P-gp to translocate out of lipid rafts. RTX
      chemosensitized 2 different MDR cell lines, inhibited the activity of P-gp in
      both, and induced P-gp to translocate out of lipid rafts in the 1 cell line that
      was studied in greater detail. In contrast, 3 other anti-CD20 antibodies did not
      chemosensitize, inhibit the activity of P-gp, or induce it to translocate out of
      rafts, despite the fact that 1 antibody recognized the same epitope on CD20. Our
      results suggest that RTX can chemosensitize 2 CD20/P-gp cell lines in vitro by
      inhibiting the activity of the P-gp pump. The inhibition of P-gp activity
      correlated with the ability of RTX to induce P-gp to translocate out of lipid
      rafts. Although the mechanisms by which RTX effects P-gp translocation and
      activity are not yet known, they are not associated with acid-sphingomyelinase
      activation in raft microdomains, as described for the antiproliferative activity
      of RTX.

PMID- 16971810
TI  - Dendritic cells loaded with killed allogeneic melanoma cells can induce objective
      clinical responses and MART-1 specific CD8+ T-cell immunity.
AB  - Dendritic cells (DCs) loaded with killed allogeneic tumors can cross-prime tumor
      specific naive CD8 T cells in vitro, thereby providing an option to overcome
      human leukocyte antigen restriction inherent to loading DC vaccines with
      peptides. We have vaccinated 20 patients with stage IV melanoma with autologous
      monocyte-derived DCs loaded with killed allogeneic Colo829 melanoma cell line.
      DCs were generated by culturing monocytes with granulocyte macrophage-colony
      stimulating factor (granulocyte macrophage-colony stimulating factor) and
      interleukin (IL-4) and activated by additional culture with tumor necrosis factor
      and CD40 ligand. A total of 8 vaccines were administered at monthly intervals.
      The first patient was accrued December 2002 and the last November 2003. Fourteen
      patients were alive at 12 months, 9 patients were alive at 24 months, and 8
      patients are alive as of January 2006. The estimated median overall survival is
      22.5 months with a range of 2 to 35.5 months. Vaccinations were safe and
      tolerable. They induced, in 2 patients who failed previous therapy, durable
      objective clinical responses, 1 complete regression (CR) and 1 partial regression
      (PR) lasting 18 and 23 months, respectively. Three out of 13 analyzed patients
      showed T-cell immunity to melanoma antigen recognized by autologous T cells (MART
      1) tissue differentiation antigen. Two of 3 patients showed improved immune
      function after vaccinations demonstrated by improved secretion of interferon
      (IFN)-gamma or T-cell proliferation in response to MART-1 derived peptides. In
      one of these patients, vaccination led to elicitation of CD8 T-cell immunity
      specific to a novel peptide-derived from MART-1 antigen, suggesting that cross
      priming/presentation of melanoma antigens by DC vaccine had occurred. Thus, the
      present results justify the design of larger follow-up studies to assess the
      clinical response to DC vaccines loaded with killed allogeneic tumor cells in
      patients with metastatic melanoma.

PMID- 16971811
TI  - Oligodeoxynucleotide CpG 7909 delivered as intravenous infusion demonstrates
      immunologic modulation in patients with previously treated non-Hodgkin lymphoma.
AB  - Oligodeoxynucleotides containing CpG motifs (CpG ODN) can alter various immune
      cell subsets important in antibody therapy of malignancy. We undertook a phase I
      trial of CPG 7909 (also known as PF-3512676) in patients with previously treated
      lymphoma with the primary objective of evaluating safety across a range of doses,
      and secondary objectives of evaluating immunomodulatory effects and clinical
      effects. Twenty-three patients with previously treated non-Hodgkin lymphoma
      received up to 3 weekly 2-hour intravenous (IV) infusions of CPG ODN 7909 at dose
      levels 0.01 to 0.64 mg/kg. Evaluation of immunologic parameters and clinical
      endpoints occurred for 6 weeks. Infusion-related toxicity included grade 1
      nausea, hypotension, and IV catheter discomfort. Serious adverse hematologic
      events observed more than once included anemia (2=Gr3, 2=Gr4), thrombocytopenia
      (4=Gr3), and neutropenia (2=Gr3), and were largely judged owing to progressive
      disease. Immunologic observations included: (1) The mean ratio of NK-cell
      concentrations compared with pretreatment at day 2 was 1.44 (95% CI=0.94-1.94)
      and at day 42 was 1.53 (95% CI=1.14-1.91); (2) NK activity generally increased in
      subjects; and (3) Antibody-dependent cellular cytotoxicity activity increased in
      select cohorts. No clinical responses were documented radiographically at day 42.
      Two subjects demonstrated late response. We conclude CpG 7909 can be safely given
      as a 2-hour IV infusion to patients with previously treated non-Hodgkin lymphoma
      at doses that have immunomodulatory effects.

PMID- 16971812
TI  - EpCAM overexpression in thyroid carcinomas: a histopathological study of 121
      cases.
AB  - Epithelial cell adhesion molecule (EpCAM) is expressed by a broad variety of
      carcinoma cells. It is recognized by the monoclonal antibody 17-1A, which has
      already been applied for immunotherapy of several carcinoma types in preclinical
      and small clinical studies. In the present study the immunohistochemical
      properties of 17-1A were evaluated in 121 cases of thyroid carcinomas of
      follicular cell origin, comprising of 75 differentiated (DTC; 35 papillary and 40
      follicular carcinomas), 24 poorly differentiated (PDTC) and 22 anaplastic thyroid
      carcinomas. Overexpression of EpCAM, as recently defined, was found with a
      distinct membranous staining pattern in 81.3% of DTCs and in 66.6% of PDTCs. In
      contrast, all anaplastic thyroid carcinomas (0%) completely lacked EpCAM
      expression. Normal thyroid tissue presented with weak and heterogeneous EpCAM
      staining. This study demonstrates EpCAM overexpression as a common finding in
      DTCs and PDTCs, and thus these tumors as possible novel targets for EpCAM
      directed immunotherapy. Our findings suggest that patients with recurrent or
      advanced tumor disease and metastatic spread could benefit from this modern
      therapeutic regime, especially after insufficient radioiodine therapy.

PMID- 16971813
TI  - The schizophrenia paradigm: a hundred-year challenge.

PMID- 16971814
TI  - Ethnicity, expressed emotion, and schizophrenia patients' perceptions of their
      family members' criticism.
AB  - Expressed emotion is a widely researched construct. However, less is known about
      patients' own perceptions of their relatives' expressed emotion. Using a sample
      of 42 patient/family member dyads with schizophrenia, we examined the concordance
      between the number of criticisms expressed by relatives during the Camberwell
      Family Interview and patients' perceptions of how critical they perceived their
      relative to be. As predicted, white and Latino family members who expressed more
      criticism during the Camberwell Family Interview were indeed perceived as more
      critical by patients. Among blacks, however, no significant association was found
      between relatives' expressed criticism and patients' perceptions of their
      relatives' criticism. Findings from this study suggest that cultural/ethnic
      values may influence how criticism from relatives is perceived and experienced by
      patients.

PMID- 16971815
TI  - Cluster B and C personality traits, symptom correlates, and treatment utilization
      in postacute schizophrenia.
AB  - Unusually high levels of Cluster B and C personality traits have been observed in
      schizophrenia. While these have been linked to poorer function, less clear is the
      association of these personality traits with symptoms and service utilization. To
      examine this issue, 46 participants with schizophrenia or schizoaffective
      disorder were administered the Millon Clinical Multiaxial Inventory, Third
      Edition, and the Positive and Negative Syndrome Scale, and an inventory was taken
      of medical and psychiatric service utilization. Two sets of multiple regression
      analyses using Cluster B and C traits to predict treatment utilization and
      symptoms revealed that emotional discomfort symptoms were significantly related
      to level of borderline traits. Higher levels of positive symptoms were linked
      with more avoidant traits and fewer dependent traits. Higher levels of negative
      symptoms were linked with greater avoidant traits. Service utilization was
      predicted by borderline, antisocial, and avoidant traits. Implications for
      rehabilitation and treatment are discussed.

PMID- 16971816
TI  - Premorbid adjustment in bipolar disorder: comparison with schizophrenia.
AB  - Knowledge that poor premorbid adjustment (PMA) precedes illness onset in many
      schizophrenia cases can facilitate early detection. Increasing consideration is
      being given to a similar early detection strategy for bipolar disorder (BPD).
      Results of this preliminary investigation comparing PMA in BPD (N = 53) and
      schizophrenia (N = 39) outpatients revealed a significant difference at the late
      adolescent (F[1,58] = 4.499, p = 0.038) stage only, with specific differences in
      two areas of PMA: adaptation to school (t [58] = 1.83, p = 0.036) and social
      sexual functioning (t [58] = 2.441, p = 0.009). However, mood state may affect
      some PMA ratings in BPD. Depression ratings were not correlated with reported
      late adolescent PMA, but a significant, positive correlation was found for the
      childhood stage (r = 0.32, p = 0.02). Findings fail to support a trend similar to
      schizophrenia of deteriorating PMA in BPD; however, the approach to
      investigations of PMA in BPD may need to be reconsidered.

PMID- 16971817
TI  - Risk factors for depression after a disaster.
AB  - Environmental stressors such as mass disasters may contribute to an increased
      prevalence of depression within the population affected. We examined the
      prevalence of probable major depression and risk factors for depression in the 6
      month period after the September 11, 2001, attacks on the World Trade Center
      among New York City (NYC) metropolitan residents. A total of 2700 persons who
      were representative of the NYC metropolitan area were included in this cross
      sectional telephone survey. The prevalence of probable major depression in the 6
      months after the attacks was 9.4%. Multivariate logistic regression covariates
      associated with the likelihood of probable major depression included being
      directly affected by the attacks, having a perievent panic attack, experiencing
      multiple life stressors, and having been exposed to previous traumatic events.
      Mass traumatic event exposure appears to be an independent environmental risk
      factor for depression in the postdisaster context; specific reactions such as
      perievent panic attacks may have prognostic value.

PMID- 16971818
TI  - Antisocial personality disorder with childhood- vs. adolescence-onset conduct
      disorder: results from the National Epidemiologic Survey on Alcohol and Related
      Conditions.
AB  - This study, based on a nationally representative, epidemiologic sample (N =
      43,093, response rate 81%), compared sociodemographic and family history
      correlates, antisocial personality disorder (ASPD) symptom patterns, and Axis I
      and Axis II comorbidity, among adults with DSM-IV ASPD who reported onset of
      conduct disorder (CD) in childhood (<age 10) versus adolescence (> or =age 10).
      Prevalence of each ASPD diagnostic criterion and comorbid lifetime disorder was
      estimated. Logistic regression was used to examine associations of childhood
      onset CD with ASPD symptom patterns and comorbid disorders. Among the 1422
      respondents with ASPD, 447 reported childhood-onset CD. Childhood-onset
      respondents were more likely than adolescence-onset respondents to endorse CD
      criteria involving aggression against persons, animals, and property before age
      15, and to endorse more childhood criteria and lifetime violent behaviors.
      Childhood-onset respondents displayed significantly elevated odds of lifetime
      social phobia, generalized anxiety disorder, drug dependence, and paranoid,
      schizoid, and avoidant personality disorders, but significantly decreased odds
      for lifetime tobacco dependence. Childhood-onset CD appears to identify a more
      polysymptomatic and violent form of ASPD, associated with greater lifetime
      comorbidity for selected Axis I and Axis II disorders, in nonclinical
      populations.

PMID- 16971819
TI  - Reliability of retrospective assessments of childhood experiences in Germany.
AB  - The retrospective assessment of adverse childhood experiences is a widely used
      technique. Few studies report heterogeneous results about the reliability and
      objectivity. A sample of 100 patients was independently interviewed by means of
      the Mainz Structured Biographical Interview by two different interviewers with
      mean time lag of 2.2 years. Reliability of reports of family situation, physical
      abuse, sexual abuse, and protective factors was assessed. The results show
      moderate to good reliability for most childhood experiences. Divorce/separation
      of parents had a kappa of .95, severe sexual abuse a kappa of .64, and regular
      harsh physical abuse a kappa of .56; protective factors were in the .50 range.
      The key features for obtaining good reliability seem to be the concreteness of
      the question and accuracy of the coding categories. There is some, but little,
      evidence that sensitive issues such as sexual abuse are more prone to errors in
      assessment than simple ones.

PMID- 16971820
TI  - Dissociation among Swedish adolescents and the connection to trauma: an
      evaluation of the Swedish version of Adolescent Dissociative Experience Scale.
AB  - The purpose of this study was to investigate the psychometric properties of the
      Swedish version of Adolescent Dissociative Experience Scale (A-DES), dissociative
      symptoms among Swedish adolescents, and dissociative symptoms connected to trauma
      and sexual and physical abuse. A normative group of 400 adolescents aged 12 to 19
      years and a clinical group of 20 adolescents with known experienced trauma were
      given A-DES. A test-retest procedure was conducted with 90 subjects from the
      normative group. The results showed good reliability, internal consistency and
      test-retest. Factor analysis in the normative sample (N = 400) resulted in a one
      factor solution. Correlation between A-DES and other measures of dissociation was
      high (r = .86). Significant differences for the total sum of A-DES were found in
      the normative group between adolescents with and without self-reported trauma and
      between the normative group and the clinical group with known experienced trauma.
      The Swedish version of A-DES was shown to be a screening instrument with
      satisfactory psychometric qualities and the capability of capturing dissociative
      symptoms in adolescents with self-reported trauma as well as clinical cases with
      identified trauma.

PMID- 16971821
TI  - Symptom improvement in co-occurring PTSD and alcohol dependence.
AB  - This study investigated the temporal course of improvement in PTSD and alcohol
      dependence symptoms among individuals participating in a 12-week outpatient
      treatment study. Participants were 94 individuals with comorbid PTSD and alcohol
      dependence enrolled in a double-blind, placebo-controlled medication trial.
      Outcome measures included PTSD symptoms (as measured by the Clinician
      Administered PTSD Scale, Impact of Events Scale, and Civilian Mississippi Scale
      for PTSD) and alcohol use severity (as measured by the Time Line Follow Back).
      Study completion rates were significantly higher for individuals who demonstrated
      improvement in both disorders. Improvements in PTSD had a greater impact on
      improvement in alcohol dependence symptoms than the reciprocal relationship.
      Improvement in hyperarousal PTSD symptoms, in particular, was related to
      substantially improved alcohol use. Examination of the temporal course of symptom
      improvement revealed that alcohol symptoms tended to start improving either
      before or in conjunction with PTSD symptoms. Although preliminary in nature,
      these findings suggest that co-occurring PTSD symptoms may have a strong impact
      on alcohol dependence treatment outcome, and that PTSD treatment may be important
      to optimizing outcomes for patients with comorbid PTSD and alcohol dependence.

PMID- 16971822
TI  - An examination of cognitive versus behavioral components of recovery from
      anorexia nervosa.
AB  - Definitions of "full recovery" from anorexia nervosa (AN) vary, and rarely
      include the cognitive criteria of lack of body image distortion and fear of
      weight gain. We investigated the implications of including or excluding cognitive
      criteria of AN in the definition of "full recovery". Current symptomatology and
      personality characteristics associated with AN were assessed and compared in 42
      behaviorally but not cognitively recovered women, 32 both behaviorally and
      cognitively recovered women, and 253 controls. On all measures included, the
      scores of the behaviorally recovered women were significantly more anorexic-like
      than those of the women recovered cognitively as well, who were indistinguishable
      from controls. Criteria for recovery from AN need to be refined and standardized,
      and cognitive criteria incorporated, to characterize a minority who recover to
      the extent that their eating attitudes and personality profiles are
      indistinguishable from those of women with no history of an eating disorder.

PMID- 16971823
TI  - Diagnosing major depressive disorder VII: family history as a diagnostic
      criterion.
AB  - Eliciting information about a patient's family history is a component of a
      standard diagnostic evaluation. Since depression runs in families, a question
      arises as to whether family history information should be considered when
      diagnosing depression. The text of DSM-IV indicates that a family history of a
      mood disorder should sometimes be considered when trying to distinguish between
      major depressive disorder and other conditions such as catatonic schizophrenia.
      The questions posed herein are how well family history of depression performs as
      a diagnostic criterion, and how its performance compares with the DSM-IV symptom
      criteria. One thousand eight hundred psychiatric outpatients were evaluated with
      a semistructured diagnostic interview as part of a research assessment
      infrastructure that has been embedded in the Rhode Island Hospital Department of
      Psychiatry outpatient practice. Family history diagnoses were based on
      information provided by the patient. The interview followed the guide provided in
      the Family History Research Diagnostic Criteria. We constructed a continuum of
      family history morbidity based on the number of first-degree family members with
      a history of depression and whether the family member was treated for their
      depression. Thus, we determined the presence or absence of the family history
      diagnostic criterion in different ways. Family history information was collected
      on 9763 first-degree relatives of 1776 patients. The sensitivity of the family
      history criterion was lower than each of the symptoms. Based on the broadest
      definition of the family history variable, the specificity was also lower than
      all other symptoms. Based on the narrowest definition (two or more family members
      who were treated for depression), the specificity was higher than all of the
      symptom criteria though sensitivity dropped to 15%. Overall, as a diagnostic
      criterion, a family history of depression did not perform as well as the DSM-IV
      symptom criteria. Consistent with the familial nature of depression, the family
      history variable performed better as a diagnostic criterion when considering
      diagnosis from a lifetime, rather than a current, perspective. This has
      implications for the future consideration of genetic markers as diagnostic
      criteria.

PMID- 16971824
TI  - Gender, sex role ideology, and self-esteem among East Asian immigrants in the
      United States.
AB  - This study examined the relationship between gender, sex role ideology, and self
      esteem among 170 (88 male, 82 female) East Asian immigrants in the United States.
      Participants were administered a battery of psychometrically established
      measures. Men and women did not differ on personal or collective self-esteem
      (CSE). Women who endorsed traditional sex roles were significantly more likely to
      report higher private, identity, and total CSE. Personal self-esteem was a
      significant independent predictor of traditional sex role for women. Participants
      who endorsed sex role equality were significantly more likely to report public,
      membership, and total CSE. Sex role equality was associated with enhanced private
      CSE for men and attenuated personal self-esteem for women. These findings point
      to the importance of assessing multiple facets of self-esteem, which appear to be
      differentially associated with sex role ideology for men and women.

PMID- 16971825
TI  - Predictors of binge eating in restrictive anorexia nervosa patients in Italy.
AB  - The aim of the present study was to investigate the predictive factors for the
      development of binge eating in restricting anorexia nervosa patients who
      underwent an outpatient treatment. The sample was a group of 168 patients with
      restricting anorexia nervosa, consecutively admitted to an outpatient unit. All
      the patients underwent a routine baseline assessment. Information regarding binge
      eating onset and duration of treatment was prospectively recorded in clinical
      records. Twenty-three patients developed binge episodes during outpatient
      treatment. High scores on the Eating Disorders Inventory body dissatisfaction
      subscale and early age at menarche significantly predict the risk of developing
      binge eating. High levels of ineffectiveness, as measured by the Eating Disorders
      Inventory, and early age at menarche are significant predictors of a shortened
      time to develop binge eating. The identification of subjects at risk for
      developing binge eating should be considered an important step for a successful
      treatment of restricting anorexic patients.

PMID- 16971826
TI  - Solutions to discrimination in work and housing identified by people with mental
      illness.
AB  - Several studies have examined the breadth and depth of the impact of the stigma
      and discrimination associated with mental illness. This study examines perceived
      solutions to discrimination in housing and employment situations. We expected
      identification of solutions to be positively associated with disease insight and
      personal empowerment. One hundred people with serious mental illness completed
      measures of perceived solutions to discrimination exhibited by an employer or a
      landlord. They also completed measures of empowerment and insight. Results showed
      high frequency solutions included looking for a job or apartment elsewhere, or
      seeking help from family and friends. Insight was significantly associated with
      number of endorsed solutions, while the interaction between insight and
      empowerment described a nonsignificant trend. Implications of these findings for
      stigma change are discussed.

PMID- 16971827
TI  - Not going for checkups-Is it a guy thing?

PMID- 16971828
TI  - Preparation makes the difference in loan approval process.

PMID- 16971829
TI  - Prostate cancer: prevention and management of localized disease.

PMID- 16971831
TI  - Shedding light on Alzheimer's.

PMID- 16971833
TI  - Managing bronchospasm with short-acting beta(2)-agonists.

PMID- 16971834
TI  - Erectile dysfunction.

PMID- 16971837
TI  - The practice of optometry: National Board of Examiners in Optometry survey of
      optometric patients.
AB  - PURPOSE: A study commissioned by the National Board of Examiners in Optometry was
      designed to obtain information about patients seen in general practice. METHODS:
      Providers completed an encounter form for patients seen during a 2-day sample.
      Data were obtained from 11,012 patients in rural, urban, and suburban
      environments from a diverse population of 480 optometrists representative of
      profession-wide practitioners in terms of geographic distribution and practice
      settings. Although practitioners were randomly selected, the response rate among
      those who were invited to participate was only 17.7%. Optometrists who
      specialized and did not classify themselves as general practitioners were
      excluded from the study. RESULTS: The study provides insights into the most
      common diagnostic and therapeutic procedures performed, medications prescribed,
      and referrals made in general practices. Seventy-one percent of all examinations
      were categorized as comprehensive eye examinations, approximately 13% the result
      of disease, and 11% was for contact lens care. Almost 17% of all patients
      received a formal visual field test (Goldmann or automated). Refractive error was
      the most prevalent diagnosis reflective of the ocular problems found in the
      general population and systemic conditions were the second largest category.
      Although 12% of all patients were referred to an ophthalmologist for further
      care, other types of referrals were infrequent. Referrals to a primary care
      physician, laboratory, and imaging or for refractive surgery accounted for only
      8% of all referrals. CONCLUSION: Ocular disease treatment was found to be an
      integral part of the optometrist's practice. Prescribing topical medications,
      both legend and "over the counter," was a primary treatment option. The most
      common medications prescribed were for glaucoma, with antibiotics,
      antiinflammatory, and antiallergy drops making up the remainder in descending
      order.

PMID- 16971838
TI  - Effect of tilt on the tilted power vector of a thin lens.
AB  - PURPOSE: The purpose of this study is to derive the equation for the effect of
      tilt on the tilted power vector of a possibly astigmatic thin lens. METHODS: The
      analysis makes use of the equation for tilted power in terms of the dioptric
      power matrix. RESULTS: A simple equation is obtained for the tilted power vector
      of a thin lens in terms of the untilted power vector of the lens. A solution of
      the equation provides a means for compensating spectacle lenses for tilt.
      Numerical examples are presented in the (available online at www.optvissci.com).
      CONCLUSIONS: The equation gives insight and is useful for researchers and
      clinicians working in terms of power expressed as power vectors.

PMID- 16971839
TI  - Exploring new paths to reveal today's general practice of optometry.

PMID- 16971841
TI  - Metrics of retinal image quality predict visual performance in eyes with 20/17 or
      better visual acuity.
AB  - PURPOSE: The purpose of this study is to determine the ability of single-value
      metrics of retinal image quality of the eye to predict visual performance as
      measured by high (HC) and low (LC) -contrast acuity at photopic (P) and mesopic
      (M) light levels in eyes with 20/17 and better visual acuity. METHODS: Forty-nine
      normal subjects in good health ranging in age from 21.8 to 62.6 with 20/17 or
      better monocular high-contrast logarithm of the minimum angle of resolution
      (logMAR) acuity served as subjects. Wavefront error through the 10th Zernike
      radial order over a 7-mm pupil was measured on each test eye using a custom-built
      Shack/Hartmann wavefront sensor. For each eye, 31 different single-value retinal
      image quality metrics were calculated. Visual acuity was measured using HC (95%)
      and LC (11%) logMAR at photopic (270 cd/m) and mesopic (0.75 cd/m) light levels.
      To determine the ability of each metric of retinal image quality to predict each
      type of logMAR acuity (P HC, P LC, M HC, and M LC), each acuity measure was
      regressed against each optical quality metric. RESULTS: The ability of the
      metrics of retinal image quality to predict logMAR acuity improved as luminance
      and/or contrast is lowered. The best retinal image quality metric (logPFSc)
      accounted for 2.6%, 15.1%, 27.6%, and 40.0% of the variance in P HC, P LC, M HC,
      and M LC logMAR acuity, respectively. CONCLUSIONS: In eyes with 20/17 and better
      P HC acuity, P HC logMAR acuity is insensitive to variations in retinal image
      quality compared with M LC logMAR acuity. Retinal image quality becomes
      increasingly predictive of logMAR acuity as contrast and/or luminance is
      decreased. Everyday life requires individuals to function over a large range of
      contrast and luminance levels. Clinically, the impact of retinal image quality as
      a function of luminance and contrast is readily measurable in a time-efficient
      manner with M LC logMAR acuity charts.

PMID- 16971842
TI  - Peripheral refraction in orthokeratology patients.
AB  - PURPOSE: The purpose of this study is to measure refraction across the horizontal
      central visual field in orthokeratology patients before and during treatment.
      METHODS: Refractions were measured out to 34 degrees eccentricity in both
      temporal and nasal visual fields using a free-space autorefractor (Shin-Nippon
      SRW5000) for the right eyes of four consecutively presenting myopic adult
      patients. Measurements were made before orthokeratology treatment and during the
      course of treatment (usually 1 week and 2 weeks into treatment). Refractions were
      converted into mean sphere (M), 90 degrees to 180 degrees astigmatism (J180), and
      45 degrees to 135 degrees astigmatism (J45) components. RESULTS: Before
      treatment, subjects had either a relatively constant mean sphere refraction
      across the field or a relative hypermetropia in the periphery as compared with
      the central refraction. As a result of treatment, myopia decreased but at reduced
      rate out into the periphery. Most patients had little change in mean sphere at 30
      degrees to 34 degrees . In all patients, the refraction pattern altered little
      after the first week. CONCLUSION: Orthokeratology can correct myopia over the
      central +/- 10 degrees of the visual field but produces only minor changes at
      field angles larger than 30 degrees . If converting relative peripheral
      hypermetropia to relative peripheral myopia is a good way of limiting the axial
      elongation that leads to myopia, orthokeratology is an excellent option for
      achieving this.

PMID- 16971843
TI  - Potential effect on the retinoscopic reflex of scleral expansion surgery for
      presbyopia.
AB  - PURPOSE: In this initial study, we model the impact of crystalline lens movement
      and tilt, which we postulate are a potential consequence of scleral expansion
      surgery (SES). We demonstrate the possibility that these lead to an improvement
      in near vision with no concurrent restoration of lens accommodative function.
      With the implantation of scleral expansion bands (SEB), Schachar predicts an
      increase in the amplitude of accommodation not observed objectively. We postulate
      that the SEB implants cause the crystalline lens to be shifted forward and become
      misaligned. Using mathematical models of the optics of the human eye, we assess
      the effects of our postulate on the power of the eye, the depth of field, optical
      aberrations, and the appearance of the horizontal retinoscopic reflex. METHODS:
      Using anatomically based models of the human eye, the postulated effects of SES
      are theoretically modeled and optically analyzed in Code V for unintentional lens
      anterior movement, tilts, and decentrations of up to 1 mm, +/- 3 degrees , and +/
      0.3mm, respectively. The transverse aberrations are calculated before and after
      SES. Because it has been reported that the appearance of the retinoscopic reflex
      is consistent with the presence of excess aberrations, we also predict the
      appearance of the one-dimensional retinoscopic reflex for our models. The change
      in refractive error is also determined. RESULTS.: Unintentional lens shift, tilt,
      and decentration, as might occur as a result of SES surgery, would result in an
      increase in the total power of the eye along with an increase in asymmetric
      aberrations and little change in symmetric aberrations. The calculated
      appearances of the retinoscopic reflexes pre- and postsurgery are consistent with
      observations in the literature. CONCLUSIONS: Scleral expansion surgery could
      produce an improvement in near vision through an unintentional anterior
      displacement of the crystalline lens in combination with excess tilts and
      decentrations rather than as a result of a restoration of lens accommodation.
      There is a need for measurements and further analysis of the optical and visual
      properties of SES patients postsurgery.

PMID- 16971844
TI  - Simultaneous measurements of refraction and A-scan biometry during accommodation
      in humans.
AB  - PURPOSE: Accommodation is a dioptric change in power of the crystalline lens
      resulting from ciliary muscle contraction that leads to an increase in lens
      surface curvatures and thickness and changes in the position of lens surfaces.
      Previous studies have used A-scan ultrasound to measure changes in the position
      of lens surfaces with voluntary accommodation, but have not simultaneously
      measured the change in refraction. The goal of this study is to simultaneously
      measure and correlate refractive and biometric changes in the lens during
      voluntary accommodation in humans. METHODS: Refraction was measured off-axis in
      the right eye and biometry on-axis in the left eye simultaneously during
      voluntary accommodation in 22 human subjects between the ages of 21 and 30 years
      (mean +/- standard deviation: 25.8 +/- 2.3 years). Subjects viewed a distant
      target and four near targets spanning the full accommodative range available to
      evaluate refraction and lens surface position at each accommodative state.
      RESULTS: Maximum objectively measured accommodative amplitude of all subjects was
      5.64 +/- 0.21 D (mean +/- standard error of mean). Biometric and refractive
      changes during accommodation were linearly correlated. The mean +/- standard
      error of mean decrease in anterior chamber depth was 0.051 +/- 0.008 mm/D,
      increase in lens thickness was 0.067 +/- 0.008 mm/D, and increase in anterior
      segment length was 0.017 +/- 0.005 mm/D during accommodation. There was a net
      anterior movement of the lens center of 0.017 +/- 0.005 mm/D. CONCLUSION:
      Anterior chamber depth, lens thickness, and anterior segment length change
      linearly with refraction during accommodation. Per-diopter changes in the lens
      were greater in the current study compared with previous studies in which only
      accommodative demand was measured, which overestimates the accommodative
      response.

PMID- 16971845
TI  - An analytical model describing aberrations in the progression corridor of
      progressive addition lenses.
AB  - PURPOSE: In the progression corridor of a typical progressive addition lens (PAL)
      with an addition of 2.5 D, the power changes by roughly 1/8 D/mm. This renders a
      power difference of some 0.5 D across a typical pupil diameter of 4 mm. Contrary
      to this fact, PALs do work well in the progression zone. To explain why, we apply
      a simple model to derive wavefront characteristics in the progression zone and
      compare it with recent experimental data. METHODS: We consider a simple analytic
      function to describe the progression zone of a PAL, which has been introduced by
      Alvarez and other authors. They considered the power change and astigmatism,
      which are second-order wavefront aberrations. We include third-order aberrations
      and compare them with spatially resolved wavefront data from Hartmann-Shack
      sensor measurements. RESULTS: The higher-order aberrations coma and trefoil are
      the dominant aberrations besides astigmatism as given by experimental data.
      According to our model, the third-order aberrations in the transition zone are
      strongly coupled to the power change and the cubic power of the pupil radius.
      Their overall contribution according to experimental data is nicely reproduced by
      our model. The numeric contribution of higher-order aberrations is small and, for
      practical purposes, the wavefront can be described locally by the second-order
      components of sphere and astigmatism only. CONCLUSIONS: We propose a simple
      analytical model to understand the optics in the progression corridor and nearby
      zones of a PAL. Our model confirms that for typical pupil sizes, all higher-order
      aberrations, including the dominant modes of coma and trefoil, are small enough
      to render an undisturbed vision in the progression zone. Therefore, higher-order
      aberrations have a minimal impact on the optical performance of these lenses.

PMID- 16971846
TI  - Visual acuity and optical parameters in progressive-power lenses.
AB  - PURPOSES: The purposes of this study are to explore the effect of astigmatism and
      high-order aberrations of progressive-power lenses (PPLs) on visual acuity (VA)
      and to find a good optical metric for evaluating visual performance of PPLs.
      METHODS: A Hartmann-Shack (HS) wavefront sensor was used to measure PPLs and
      human eyes either independently or in combination. An additional channel permits
      the measurement of VA under the same optical conditions. Measurements were taken
      in six relevant locations of a PPL and in three eyes of different normal
      subjects. In every case, we obtained the wavefront aberration as Zernike
      polynomials expansions, the root mean square (RMS) error, and two metrics on
      point spread function (PSF): Strehl ratio and the common logarithm of the volume
      under the PSF normalized to one (Log_Vol_PSF). RESULTS: Aberration coupling of
      the PPL with the eye tends to equalize the retinal image quality between central
      and peripheral zones of the progressive lenses. In the corridor of the PPL, the
      combination of small amounts of coma, trefoil, and astigmatism (total RMS 0.1
      mum) does not significantly affect VA. The continuous increase of astigmatism
      from corridor to outside zones reduces moderately the quality of vision. The
      highest correlations between optical metrics and VA were found for Log_Vol_PSF of
      the entire system eye plus PPL. CONCLUSIONS: Ocular aberrations reduce optical
      quality difference between corridor and peripheral zones of PPLs. In the same
      way, VA through the corridor is similar to that of eyes without a lens and it
      decreases slowly toward peripheral locations. VA through PPLs is well predicted
      by the logarithm of metrics directly related with image spread (Log_Vol_PSF or
      equivalent) of the complete system of the eye with the lens.

PMID- 16971847
TI  - Simulation of machine-specific topographic indices for use across platforms.
AB  - PURPOSE: The objective of this project is to simulate the current published
      topographic indices used for the detection and evaluation of keratoconus to allow
      their application to maps acquired from multiple topographic machines. METHODS: A
      retrospective analysis was performed on 21 eyes of 14 previously diagnosed
      keratoconus patients from a single practice using a Tomey TMS-1, an Alcon EyeMap,
      and a Keratron Topographer. Maps that could not be processed or that contained
      processing errors were excluded from analysis. Topographic indices native to each
      of the three devices were recorded from each map. Software was written in ANSI
      standard C to simulate the indices based on the published formulas and/or
      descriptions to extend the functionality of The Ohio State University Corneal
      Topography Tool (OSUCTT), a software package designed to accept the input from
      many corneal topographic devices and provide consistent display and analysis.
      Twenty indices were simulated. Linear regression analysis was performed between
      each simulated index and the corresponding native index. A cross-platform
      comparison using regression analysis was also performed. RESULTS: All simulated
      indices were significantly correlated with the corresponding native indices (p <
      0.01), with a mean R of 0.84, ranging from 0.42 to 0.99. Cross-platform
      comparisons were nonsignificant for specific indices and devices. CONCLUSION:
      Topographic indices native to three devices were successfully simulated. Cross
      platform comparisons may be limited for specific indices.

PMID- 16971848
TI  - Preclinical trial of L-arginine monotherapy alone or with N-acetylcysteine in
      septic shock.
AB  - OBJECTIVE: L-arginine supplementation in sepsis is controversial. Septic shock
      has been alternatively viewed as an L-arginine-deficient state or as a syndrome
      caused by excess nitric oxide, an end-product of L-arginine metabolism. DESIGN:
      Randomized, placebo-controlled, and double-blinded (investigators, veterinarians,
      and pharmacists). SETTING: Laboratory. SUBJECTS: Purpose-bred, 1- to 2-yr-old, 10
      to 12-kg beagles. INTERVENTIONS: The effects of parenteral L-arginine alone or
      in combination with N-acetylcysteine were compared with vehicle alone in a well
      characterized canine model of Escherichia coli peritonitis. Two doses were
      studied that delivered approximately 1.5-fold (10 mg x kg(-1) x hr(-1)) and 15
      fold (100 mg x kg(-1) x hr(-1)) the L-arginine dose typically administered with
      standard total parenteral nutrition. Animals in the low- and high-dose L-arginine
      arms were further randomized to receive vehicle alone or N-acetylcysteine (20 mg
      x kg(-1) x hr(-1)) as an antioxidant to prevent peroxynitrite formation.
      MEASUREMENTS AND MAIN RESULTS: The main measurements were hemodynamics, plasma
      arginine and ornithine, serum nitrate/nitrite, laboratory studies for organ
      injury, and survival. Both doses of L-arginine similarly increased mortality (p =
      .02), and worsened shock (p = .001 for reduced mean arterial pressure). These
      effects were associated with significant increases in plasma arginine (p = .0013)
      and ornithine (p = .0021). In addition, serum nitrate/nitrite (p = .02), liver
      enzymes (p = .08), and blood urea nitrogen/creatinine ratios (p = .001) rose,
      whereas arterial pH (p = .001) and bicarbonate levels (p = .001) fell. N
      acetylcysteine did not significantly decrease any of the harmful effects of L
      arginine. Thus, parenteral L-arginine monotherapy was markedly harmful in animals
      with septic shock. CONCLUSIONS: These findings suggest that supplemental
      parenteral L-arginine, at doses above standard dietary practices, should be
      avoided in critically ill patients with septic shock.

PMID- 16971849
TI  - Hemodynamic effects of different lung-protective ventilation strategies in closed
      chest pigs with normal lungs.
AB  - OBJECTIVE: The benefits of lung-protective ventilation strategies used for acute
      respiratory distress syndrome in subjects with normal lungs are uncertain. The
      purpose of this study was to investigate the hemodynamic effects of conventional
      lung-protective ventilation (CLPV) and high-frequency oscillatory ventilation
      (HFOV) in a normal lung animal model. DESIGN: Prospective laboratory
      investigation. SETTING: Animal laboratory in a university medical center.
      SUBJECTS: Seven landrace pigs (mean weight 41 kg). INTERVENTIONS: Pigs were
      ventilated at random conventionally with positive end-expiratory pressure 2-3 cm
      H2O and tidal volume 10-12 mL/kg (control), with CLPV (positive end-expiratory
      pressure 10 cm H2O, tidal volume 6 mL/kg), or with HFOV. Hemodynamics were
      analyzed after insertion of biventricular conductance catheters and a pulmonary
      artery catheter. MEASUREMENTS AND MAIN RESULTS: The protective strategies led to
      higher mean airway pressures and severe hypercapnia with acidosis, which was only
      significant with CLPV. Compared with control, oxygenation was worse with CLPV and
      HFOV. With HFOV and CLPV, mean arterial pressure, cardiac output, and stroke
      volume decreased significantly; pulmonary arterial elastance increased. The slope
      of the end-diastolic pressure volume relationship for the left and right
      ventricle remained unchanged (preserved ventricular function), whereas the
      intercept increased with both protective strategies (augmented intrathoracic
      pressure); left and right end-diastolic volumes decreased significantly.
      CONCLUSIONS: In the absence of a fluid resuscitation strategy, CLPV and HFOV
      caused decreased mean arterial pressure, cardiac output, and stroke volume and
      worsened oxygenation in this normal lung animal model. This resulted primarily
      from a biventricular decrease in preload.

PMID- 16971850
TI  - Opposed effects of hypertonic saline on contusions and noncontused brain tissue
      in patients with severe traumatic brain injury.
AB  - OBJECTIVE: The aim of this study was to quantify the effect of hypertonic saline
      solution on contused and noncontused brain tissue in patients with traumatic
      brain injury. We hypothesize that hypertonic saline would increase the volume of
      brain contusion while decreasing the volume of noncontused hemispheric areas.
      DESIGN: Prospective observational study. SETTING: Neurosciences critical care
      unit of a university hospital. PATIENTS: Fourteen traumatic brain injury patients
      with increased intracranial pressure. INTERVENTIONS: A computed tomography scan
      was performed before and after a 20-min infusion of 40 mL of 20% saline.
      MEASUREMENTS AND MAIN RESULTS: The volume, weight, and specific gravity of
      contused and noncontused hemispheric areas were assessed from computed tomography
      DICOM images by using a custom-designed software (BrainView). Physiologic
      variables and natremia were measured before and after infusion. Hypertonic saline
      significantly increased natremia from 143 +/- 5 to 146 +/- 5 mmol/L and decreased
      intracranial pressure from 23 +/- 3 to 17 +/- 5 mm Hg. The volume of the
      noncontused hemispheric areas decreased by 13 +/- 8 mL whereas the specific
      gravity increased by 0.029 +/- 0.027%. The volume of contused hemispheric tissue
      increased by 5 +/- 5 mL without any con-comitant change in density. There was a
      wide interindividual variability in the response of the noncontused hemispheric
      tissue with changes in specific gravity varying between -0.0124% and 0.0998%.
      CONCLUSIONS: Three days after traumatic brain injury, the blood- brain barrier
      remains semipermeable in noncontused areas but not in contusions. Further studies
      are needed to tailor the use of hypertonic saline in patients with traumatic
      brain injury according to the volume of contusions assessed on computed
      tomography.

PMID- 16971851
TI  - Hemodynamic effects of combined treatment with oxygen and hypertonic saline in
      hemorrhagic shock.
AB  - OBJECTIVE: In hemorrhagic shock, small volume resuscitation with hypertonic
      saline transiently increases mean arterial blood pressure (MABP) and cardiac
      output and augments organ perfusion. Inhalation of 100% oxygen after hemorrhage
      also increases MABP and redistributes blood flow to the splanchnic and renal
      vascular beds. We evaluated hemodynamic effects of combined resuscitation with
      hypertonic saline and oxygen in shock induced by controlled bleeding in rats.
      DESIGN: Animal study. SETTING: Research laboratory. SUBJECTS: Male Sprague-Dawley
      rats. INTERVENTIONS: Animals were assigned to four hemorrhage groups that
      received posttreatment with a) normal saline; b) normal saline + 100% oxygen; c)
      hypertonic saline; d) hypertonic saline + oxygen, and a fifth sham-shock group
      that received hypertonic saline + oxygen. MEASUREMENTS AND MAIN RESULTS: Bolus
      infusion of small volume hypertonic saline markedly increased MABP (p < .001),
      hindquarter vascular resistance (p < .05), and distal aorta blood flow (p < .01).
      Hypertonic saline transiently increased superior (cranial) mesenteric artery
      (SMA) blood flow (p < .001) and small bowel perfusion (p < .01). Inhalation of
      oxygen after normal saline rapidly increased MABP (p < .01) and hindquarter
      vascular resistance (p < .02) and decreased distal aorta blood flow (p < .02) and
      perfusion of the gracilis muscle (p < .05). When given after normal saline,
      oxygen did not change SMA resistance and increased SMA flow (p < .05). The
      supplementation of oxygen after hypertonic saline did not exert additional
      effects on vascular resistance and blood flows in the two vascular beds. However,
      the combined treatment prevented the oxygen-induced decrease in distal aorta
      blood flow and gracilis muscle perfusion and maintained MABP at slightly higher
      values and SMA flow at significantly higher values than hypertonic saline alone
      until the end of the protocol (p < .01). The two hemorrhaged groups treated with
      oxygen exhibited the lowest final plasma lactate concentrations (p < .05 from
      normal saline and hypertonic saline groups). CONCLUSIONS: We suggest that early
      combined use of hypertonic saline and oxygen exerts a favorable extended profile
      of hemodynamic effects that amends shortcomings of each treatment alone in
      hemorrhagic shock.

PMID- 16971852
TI  - Variations in rates of tracheostomy in the critically ill trauma patient.
AB  - OBJECTIVE: The utility of tracheostomy to expedite weaning and prevent
      complications in patients with acute respiratory failure is actively debated,
      with many physicians holding strong opinions regarding the value and timing of
      this intervention. We postulated that these opinions would be reflected in
      significant variation in tracheostomy rates across centers. Thus, we set out
      explore the extent and potential sources of this variation among injured patients
      cared for in trauma centers in the United States. DESIGN: This is a retrospective
      cohort study. We used stratification and hierarchical multivariate analysis to
      evaluate the effect of patient and institutional characteristics on tracheostomy
      rates and variance decomposition to determine the proportion of variance across
      institutions explained by patient characteristics. SETTING: Intensive care units
      within trauma centers participating in the National Trauma Databank. PATIENTS:
      Injured patients admitted over the years 2001-2003, age >/=16 yrs, with an Injury
      Severity Score >/=9 and a diagnosis of acute respiratory failure, excluding
      patients with burn injuries and those with a severe injury to the face or neck
      who might require tracheostomy for maintenance of an airway. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: There were 17,523 patients meeting inclusion
      criteria: 4,146 (24%) underwent tracheostomy. The mean tracheostomy rate across
      centers was 19.6 per 100 hospital admissions with a range of 0-59. This variation
      persisted after stratification by age, injury mechanism, and severity. Although
      several patient and injury characteristics were predictive of tracheostomy, there
      were no identifiable institutional characteristics associated with tracheostomy.
      Patient characteristics accounted for only 14% of the variance across centers.
      CONCLUSIONS: There is significant unexplained variation in the rates of
      tracheostomy in critically injured patients with acute respiratory failure. This
      variation might reflect preconceived notions of efficacy among physicians
      practicing in the absence of evidence to guide care. The variation provides
      evidence of equipoise and emphasizes the need for a well-conducted randomized
      controlled trial to evaluate the utility of this procedure.

PMID- 16971853
TI  - Early diagnosis of thyrotoxic periodic paralysis: spot urine calcium to phosphate
      ratio.
AB  - OBJECTIVES: To identify a clinically reliable index of thyrotoxic periodic
      paralysis (TPP), a life-threatening emergency with unique and effective
      therapies. DESIGN: Diagnostic study. SETTING: University teaching hospital.
      PATIENTS: Fifty-three consecutive patients with hypokalemic paralysis during a 3
      yr period and 30 thyrotoxic patients without paralysis as the thyrotoxic control
      group. INTERVENTIONS: For patients with hypokalemic paralysis, blood and second
      void spot urine samples were obtained and measured by routine laboratory prior to
      therapy. For the thyrotoxic control group, blood and spot urine were collected
      when they visited outpatient clinics. MEASUREMENTS AND MAIN RESULTS: Twenty-nine
      patients fulfilled the criteria for TPP. Compared with the thyrotoxic control
      group, the TPP group had significant decreases in plasma potassium (K) and
      phosphate concentrations associated with very low urine K and phosphate
      excretion. Compared with the non-TPP group, the TPP group had significantly lower
      plasma creatinine and phosphate levels, a significantly higher urine calcium to
      creatinine ratio (0.25 +/- 0.12 vs. 0.08 +/- 0.07 mg/mg, p < .001), and a
      significantly lower urine phosphate to creatinine ratio (0.08 +/- 0.05 vs. 0.31
      +/- 0.23 mg/mg, p < .001). The urine calcium to phosphate ratio had greater
      discriminatory power between TPP and non-TPP hypokalemic paralysis (4.1 +/- 2.3
      vs. 0.5 +/- 0.6 mg/mg, p < .001). Using a urine calcium to phosphate ratio cutoff
      value of 1.7 mg/mg, sensitivity and specificity for TPP were 100% and 96%,
      respectively. CONCLUSIONS: Hypercalciuria and hypophosphaturia are characteristic
      features of TPP.

PMID- 16971854
TI  - Effects of levosimendan versus dobutamine on pressure load-induced right
      ventricular failure.
AB  - OBJECTIVE: A transient increase in pulmonary arterial (PA) pressure can
      persistently depress right ventricular (RV) contractility. We investigated the
      effects of dobutamine and levosimendan on RV-PA coupling in this model of RV
      failure. DESIGN: Prospective, controlled, randomized animal study. SETTING:
      University research laboratory. SUBJECTS: Fifteen anesthetized dogs.
      INTERVENTIONS: Transient (90-min) PA constriction to induce persistent RV
      failure. Random assignment to dobutamine 5 and 10 microg/kg/min or levosimendan
      12 microg/kg for 10 mins followed by 0.1 and 0.2 microg/kg/min. MEASUREMENTS AND
      MAIN RESULTS: We measured PA distal resistance and proximal elastance by pressure
      flow relationships and vascular impedance. We measured RV contractility by the
      end-systolic pressure-volume relationship (Ees), PA effective elastance by the
      end-diastolic to end-systolic relationship (Ea), and RV-PA coupling efficiency by
      the Ees/Ea ratio. PA constriction persistently increased PA resistance and
      elastance, increased Ea from 0.95 +/- 0.07 to 3.01 +/- 0.28 mm Hg/mL, decreased
      Ees from 1.17 +/- 0.09 to 0.58 +/- 0.07 mm Hg/mL, and decreased Ees/Ea from 1.26
      +/- 0.09 to 0.22 +/- 0.03 (p < .05). Dobutamine did not affect pulmonary
      hemodynamics, markedly increased RV contractility, and improved RV-PA coupling.
      Levosimendan decreased PA resistance and elastance, increased RV contractility,
      and restored RV-PA coupling. Compared with dobutamine, levosimendan decreased RV
      afterload and therefore better restored RV-PA coupling at similar inotropic
      state. CONCLUSIONS: A transient increase in PA pressure persistently worsens PA
      hemodynamics, RV contractility, RV-PA coupling, and cardiac output. Levosimendan
      restores RV-PA coupling better than dobutamine because of similar inotropic
      effects and additional pulmonary vasodilatory effects.

PMID- 16971855
TI  - The effects of saline or albumin resuscitation on acid-base status and serum
      electrolytes.
AB  - OBJECTIVE: To test whether fluid resuscitation with normal saline or 4% albumin
      is associated with differential changes in acid-base status and serum
      electrolytes. DESIGN: Nested cohort study. SETTING: Three general intensive care
      units. PATIENTS: Six hundred and ninety-one critically ill patients.
      INTERVENTIONS: Randomization of patients to receive blinded solutions of either
      4% human albumin or normal saline for fluid resuscitation. MEASUREMENTS AND MAIN
      RESULTS: Albumin was given to 339 patients and saline to 352. At baseline, both
      groups had a similar serum bicarbonate, albumin, and base excess levels. After
      randomization, bicarbonate and base excess increased significantly and similarly
      over time (p < .0001). On multivariate analysis, fluid resuscitation with albumin
      predicted a smaller increase in pH (p = .0051), bicarbonate (p = .034), and base
      excess (p = .015). The amount of fluid was an independent predictor of pH (p <
      .0001), serum chloride (p < .0001), calcium (p = .0001), bicarbonate (p = .0002),
      and base excess (p < .0001) on the first day of treatment. In patients who
      received >3 L of fluids in the first 24 hrs, albumin administration was
      associated with a significantly greater increase in serum chloride (p = .0026).
      Acute Physiology and Chronic Health Evaluation II score and the presence of
      sepsis also independently predicted changes in several electrolytes and acid-base
      variables. CONCLUSIONS: When comparing albumin and saline, the choice and amount
      of resuscitation fluid are independent predictors of acid-base status and serum
      electrolytes. When large volumes are given, albumin administration leads to a
      higher chloride concentration. However, overall differences between the types of
      fluid are minor, whereas the volume of fluid administered is a much stronger
      predictor of such changes, which are also influenced by illness severity and the
      passage of time.

PMID- 16971856
TI  - Neuronal damage in rat brain and spinal cord after cardiac arrest and massive
      hemorrhagic shock.
AB  - OBJECTIVE: Severe global ischemia often results in severe damage to the central
      nervous system of survivors. Hind-limb paralysis is a common deficit caused by
      global ischemia. Until recently, most studies of global ischemia of the central
      nervous system have examined either the brain or spinal cord, but not both.
      Spinal cord damage specifically after global ischemia has not been studied in
      detail. Because the exact nature of the neuronal damage to the spinal cord and
      the differences in neuronal damage between the brain and spinal cord after global
      ischemia are poorly understood, we developed a new global ischemia model in the
      rat and specifically studied spinal cord damage after global ischemia. Further,
      we compared the different forms of neuronal damage between the brain and spinal
      cord after global ischemia. DESIGN: Randomized, controlled study using three
      different global ischemia models in the rat. SETTING: University research
      laboratory. SUBJECTS: Male, adult Sprague-Dawley rats (300 g). INTERVENTIONS:
      Animals were divided into three experimental groups, group A (n = 6, survived for
      7 days), 12 mins of hemorrhagic shock; group B (n = 6, survived for 7 days), 5
      mins of cardiac arrest; or group C (n = 6, each for 6 hrs, 12 hrs, 1 day, 3 days,
      and 7 days), 7 mins of hemorrhagic shock and 5 mins of cardiac arrest. Motor
      deficit of the hind limbs was studied 6 hrs to 7 days after resuscitation. Also,
      nonoperated animals (n = 6) were used as the control. Histologic analysis
      (hematoxylin and eosin, Fluoro-Jade B, terminal deoxynucleotidyl transferase-
      mediated dUTP end-labeling [TUNEL], Kluver-Barrera) and ultrastructural analysis
      using electron microscopy were performed on samples from the CA1 region of the
      hippocampus and lumbar spinal cord. Demyelination of the white matter of the
      lumbar spinal cord was analyzed semiquantitatively using Scion Image software.
      MAIN RESULTS: No paraplegic animals were observed in either group A or B. All
      group C animals showed severe hind-limb paralysis. Severe neuronal damage was
      found in the CA1 region of the hippocampus in all groups, and the state of
      delayed neuronal cell death was similar among the three groups. Neuronal damage
      in the lumbar spinal cord was detected only in group C animals, mainly in the
      dorsal horn and intermediate gray matter. Demyelination was prominent in the
      ventral and ventrolateral white matter in group C. A significant difference was
      observed between control and group C rats with Scion Image software.
      Ultrastructural analysis revealed extensive necrotic cell death in the
      intermediate gray matter in the lumbar spinal cord in group C rats. CONCLUSION:
      The combination in the global ischemia model (i.e., hemorrhagic shock followed by
      cardiac arrest) caused severe neuronal damage in the central nervous system.
      Thereby, hind-limb paralysis after global ischemia might result from spinal cord
      damage. These results suggest that therapeutic strategies for preventing spinal
      cord injury are necessary when treating patients with severe global ischemia.

PMID- 16971857
TI  - Abdominal lymph flow in an endotoxin sepsis model: influence of spontaneous
      breathing and mechanical ventilation.
AB  - OBJECTIVE: Lymph flow from the abdomen was investigated in a sepsis model. We
      also compared the effect on thoracic duct lymph flow of mechanical ventilation
      with different levels of positive end-expiratory pressure (PEEP) and spontaneous
      breathing with continuous positive airway pressure (CPAP). DESIGN: Experimental
      study. SETTING: Research laboratory in a university hospital. SUBJECTS: Thirty
      two pigs. INTERVENTIONS: Animals were anesthetized. In study 1 (n = 18), an
      ultrasonic flow probe was put around the intact thoracic duct just caudal to the
      diaphragm, and animals were randomized to receive mechanical ventilation with a
      PEEP of 5 cm H2O or 15 cm H2O or breathed spontaneously in CPAP with a PEEP of 5
      cm H2O. In study 2 (n = 6), the thoracic duct was cannulated and the cannula
      externalized through the abdominal wall for lymph collection; animals were then
      ventilated as in study 1. In all animals, endotoxin was infused at 15
      microg/kg/hr for 2.5 hrs and then continued at 5 microg/kg/hr. In study 3,
      healthy (n = 4) and endotoxin-exposed (n = 4) pigs had intra-abdominal pressure
      increased to 27 cm H2O for 2 hrs by pneumoperitoneum. Lymph flow was measured as
      in study 1. MEASUREMENTS AND MAIN RESULTS: Lymph flow (mean +/- SE) was 2.5 +/-
      0.4 mL/min at baseline and increased to 3.9 +/- 0.8 mL/min after 90 mins and 6.3
      +/- 1.6 mL/min after 150 mins (p < .005) of endotoxin exposure. PEEP 15 cm H2O
      decreased lymph flow in pigs with intact thoracic duct (flow probe recording) and
      in pigs with cannulated lymph duct when drained against the central venous
      pressure. However, when drained against atmospheric pressure, PEEP increased
      flow. Spontaneous breathing increased flow both in intact and in cannulated
      animals. CONCLUSIONS: Endotoxin increases lymph flow from the abdomen. Mechanical
      ventilation with high PEEP impedes lymph drainage and could increase lymph
      production. Spontaneous breathing increases flow and improves drainage of
      abdominal edema.

PMID- 16971858
TI  - Attenuation of capillary leakage by hydroxyethyl starch (130/0.42) in a porcine
      model of septic shock.
AB  - OBJECTIVES: Capillary leakage, a frequent complication in septic shock, is
      characterized by loss of intravasal fluid resulting in generalized edema and
      hemodynamic instability despite massive fluid therapy. We have shown that
      administration of an established colloid 200/0.5 hydroxyethyl starch (HES)
      stabilized plasma volume in a porcine septic shock model. Recently, a new HES
      with a low molecular weight (130 kD) and lower molar substitution (0.42) has been
      developed. In this study, we compared effects of HES 130/0.42 and HES 200/0.5 on
      capillary leakage in porcine septic shock. DESIGN: Prospective randomized,
      controlled animal study. SETTING: University department of anesthesiology.
      SUBJECTS: Fourteen pigs (22.9 +/- 2.8 kg). INTERVENTIONS: Anesthetized and
      mechanically ventilated pigs were observed over 6 hrs. MEASUREMENT AND MAIN
      RESULTS: Septic shock was induced with fecal peritonitis (0.75 g.kg of body
      weight autologous feces). Animals were allocated to volume-replacement therapy
      with either HES 130/0.42 (n = 5) or HES 200/0.5 (n = 5) and compared with
      nonseptic controls receiving HES 130/0.42 (n = 4). Infusion rate was titrated to
      maintain a central venous pressure of 12 mm Hg. Albumin escape rate was
      calculated using iodine 125-labeled albumin. Plasma volume was determined using
      chromium-51-tagged erythrocytes. Albumin escape rate increased significantly in
      both groups in comparison to controls (HES 200/0.5, 45% +/- 3; HES 130/0.42, 38%
      +/- 5), but this increase was significantly smaller with HES 130/0.42. Both HES
      200/0.5 (-14%, not significant) and HES 130/0.42 (-1%, not significant)
      stabilized plasma volume compared with controls. Systemic oxygenation was not
      significantly altered in either group. CONCLUSIONS: In this porcine septic shock
      model, HES 130/0.42 attenuated capillary leakage significantly more effectively
      than HES 200/0.5.

PMID- 16971859
TI  - Three-year survival after four major post-cardiac operative complications.
AB  - OBJECTIVE: After cardiac surgery, major morbidities known to be primary
      contributors to perioperative mortality are cardiac failure, respiratory failure,
      renal failure, and the need for mediastinal exploration. The first aim of this
      study was to ascertain long-term survival in cardiac surgery patients with and
      without the occurrence of major morbidities to investigate if long-term survival
      was comparable. The second aim of this study was to evaluate the prevalences and
      risk factors related to the four major morbidities in this patient population.
      DESIGN: Retrospective observational outcome study. SETTING: Cardiothoracic
      intensive care unit at a university hospital. PATIENTS: We included 2,683 of
      3,253 consecutive cardiac surgery patients cared for in a uniform fashion.
      METHODS AND MAIN RESULTS: Perioperative mortality was significantly increased by
      the occurrence of major morbidity. In-hospital mortality was 0.7% in the absence
      of major morbidity compared with 72% when all major morbidities occurred. Three
      year mortality for the entire study population was 15%, whereas the 3-yr long
      term survival was significantly less for patients with morbidities compared with
      those without. Various independent perioperative risk factors were found for
      perioperative major morbidity and mortality. CONCLUSIONS: Successful acute
      treatment and measures to identify and reduce the risk of major morbidities are
      necessary to improve outcome. In addition, long-term follow-up and management of
      morbidities are necessary to possibly improve long-term survival.

PMID- 16971860
TI  - How much disease burden can be prevented by environmental interventions?
AB  - There is very little systematically collected evidence on the overall
      contribution of environmental risk factors to the global burden of disease. The
      World Health Organization (WHO) recently completed a comprehensive, systematic,
      and transparent estimate of the disease burden attributable to the environment
      highlighting the full potential for environmental interventions to improve human
      health. This report is the result of a systematic literature review on
      environmental risks completed by a survey of expert opinion using a variant of
      the Delphi method. More than 100 experts provided quantitative estimates on the
      fractions of 85 diseases attributable to the environment. They were asked to
      consider only the contributions of the "reasonably modifiable environment"-that
      is, the part of environment that can plausibly be changed by existing
      interventions. The report estimates that 24% of the global burden of disease was
      due to environmental risk factors. Environmental factors were judged to play a
      role in 85 of the 102 diseases taken into account. Major diseases were, for
      example, diarrheal diseases with fractions attributable to the environment of
      94%, lower respiratory infections with 41%, malaria with 42%, and unintentional
      injuries with 42%. The evidence shows that a large proportion of this
      "environmental disease burden" could be averted by existing cost-effective
      interventions such as clean water, clean air, and basic safety measures. In
      children, 34% of the disease burden is attributable to the environment, and much
      of this burden is in developing countries.

PMID- 16971867
TI  - Any role for Helicobacter pylori in gastropathies of liver disease?

PMID- 16971868
TI  - Current understandings of Helicobacter pylori, peptic ulcer and gastroesophageal
      reflux disease.
AB  - H. pylori infection is a major pathogen inducing gastric mucosal inflammation and
      causing dysregulation of normal acid inhibitory regulatory mechanisms. The
      overall effect on gastric acid secretion is dependent on the location and
      severity of inflammation. Eradication results in healing of gastric mucosal
      inflammation, healing of peptic ulcers, prevention of new peptic ulcers,
      prevention or reduction in gastric cancer risk and in transmission of the
      infection. Neither H. pylori infection nor H. pylori eradication causes
      gastroesophageal reflux disease (GERD). H. pylori eradication also does not
      impede anti-secretory drug therapy of GERD. Misunderstandings of the negative
      association between H. pylori infection and GERD and/or Barrett's esophagus and
      misuse of the epidemiologic concept of ''protection'' led to considerable
      confusion and likely resulted in some patients receiving poor care. Current
      evidence is consistent with the notion that H. pylori should be eliminated
      whenever the organism is found. However, H. pylori infection has become
      increasing difficult to cure in part due to the emergence of antimicrobial
      resistance. In Western countries, triple therapy consisting of a proton pump
      inhibitor, amoxicillin and clarithromycin no longer achieves adequate eradication
      rates and will soon need to be abandoned. When used, legacy triple therapy should
      be given for 14 days. Fluorquinolones may temporarily be useful: 10-14 day
      duration is superior to 7 days. However, worldwide resistance is rapidly
      increasing. Other potential replacement therapies and strategies are discussed
      including sequential therapies, high-dose proton pump inhibitor plus amoxicillin,
      and new quadruple therapies.

PMID- 16971869
TI  - NSAIDs-induced gastrointestinal damage. Review.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs), along with analgesics, are the
      most widely prescribed medication in the world. However, NSAIDs cause numerous
      side effects, being the gastrointestinal (GI) events the most common ones with an
      increase of risk of serious GI complications between 2.5- and 5-fold, as compared
      with individuals not taking NSAIDs. Factors that increase the risk for serious
      events in NSAID-using patients include a history of ulcer or ulcer complications,
      advanced age (=or>65 years), the use of high-dose NSAIDs, more than one NSAID,
      anticoagulants or corticosteroid therapy. If NSAID therapy is required, we must
      balance GI and cardiovascular risk and the therapy should be prescribed at the
      lowest possible dose and for the shortest period of time. The use of NSAID
      without gastroprotective co-therapy is considered appropriate in patients<65
      years, not taking aspirin and having no GI history. In patients with GI risk
      factors, but no cardiovascular risk, coxibs or NSAIDs plus proton pump inhibitor
      (PPI) or misoprostol are valid options. Patients with a history of ulcer bleeding
      should receive coxib plus PPI therapy and should be tested and treated for
      Helicobacter pylori infection. Coxib therapy has better GI tolerance than
      traditional NSAIDs and PPI therapy is effective both in treatment and prevention
      of NSAID-induced dyspepsia and should be considered in patients who develop
      dyspepsia during NSAID or coxib therapy.

PMID- 16971870
TI  - Functional dyspepsia and non-erosive reflux disease. A review.
AB  - Functional, or non-ulcer, dyspepsia (FD) and non-erosive reflux disease (NERD),
      or endoscopy negative reflux disease are common reasons for referral to both the
      primary care physician and the gastroenterologist. Their aetiology remains
      largely obscure but both clinical and basic research have revealed much to
      suggest that these two disease entities are inextricably linked and may represent
      part of the same disease process. Several theories have been proposed to explain
      the pathophysiology of functional dyspepsia, including visceral hypersensitivity,
      delayed gastric emptying, impaired gastric fundus accommodation, Helicobacter
      pylori infection and psychosocial factors. Recent work suggests that NERD is also
      a heterogeneous disorder, with some demonstrating abnormal acid exposure and/or
      sensitivity and others entirely normal 24-h pH studies (functional heartburn). It
      would appear that the overlap of these two conditions is most apparent between FD
      and those NERD patients with normal pH studies.

PMID- 16971871
TI  - Extraesophageal manifestations in gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease (GERD) is a common condition that affects about
      20-30% of the adult population, presenting with a broad spectrum of symptoms and
      varying degrees of severity and frequency. Other manifestations are being
      increasingly recognized: the so-called ''extraesophageal'' manifestations, such
      as laryngitis, hoarseness, chronic cough, asthma, or non-cardiac chest pain.
      Epidemiological studies consistently demonstrate significant associations between
      pulmonary manifestations and GERD. Up to 50% of patients with an endoscopically
      proven esophagitis suffer from symptoms other than heartburn or acid
      regurgitation. However, the published estimates of extraesophageal disorders in
      patients with GERD vary widely, which may be a result of referral bias. The most
      effective initial approach in suspected reflux-related extraesophageal symptoms
      is empiric proton pump inhibitor (PPI) therapy. However, studies demonstrated
      that the advantage of long-term PPI treatment over placebo could have been
      overestimated.

PMID- 16971872
TI  - Anemia in inflammatory bowel disease.
AB  - Anemia is a frequent extraenteric complication of inflammatory bowel disease
      (IBD, Crohn's disease and ulcerative colitis). A systematic review of the
      literature shows that the overall prevalence of anemia ranges from 8.8% to 73.7%
      but differs whether in a setting of Crohn's disease or ulcerative colitis. A
      disabling complication of IBD, anemia worsens the patient's general condition and
      quality of life, and increases hospitalization rates. Different factors,
      including vitamin B12 and folic acid deficiency, bone marrow suppression
      secondary to drug therapy, autoimmune hemolytic anemia and the coexistence of
      myelodysplastic syndromes are involved in the pathogenesis of anemia in IBD. The
      main types of anemia in IBD are iron deficiency anemia and anemia accompanying
      chronic diseases. Correct diagnostic definition of anemia is a fundamental step
      in guiding the choice of therapeutic options, since the co-presence of different
      pathogenetic factors may sometimes require a more complex treatment plan. A
      review of anemia in IBD, its pathogenetic features, epidemiology, diagnosis and
      therapy based on evidence from recent studies is the focus of this article.

PMID- 16971873
TI  - The therapeutic role of thalidomide in inflammatory bowel disease.
AB  - Recent clinical experience with the use of thalidomide in inflammatory bowel
      disease is the focus of this article. Although widely used in Crohn's disease,
      thalidomide therapy in patients with ulcerative colitis, children with Crohn's
      disease, as well as patients with Crohn's disease associated with upper
      gastrointestinal and genital tract involvement have been occasionally reported.

PMID- 16971874
TI  - Role of Helicobacter pylori in patients with portal hypertensive gastropathy by
      liver cirrhosis hepatitis C virus-related.
AB  - AIM: Portal hypertensive gastropathy (PHG) defines a pathological endoscopic
      picture characterized by the presence of alterations of the gastric mucosa found
      in patients with hepatopathy associated to an initial or evident portal
      hypertension. Gastropathy appears with two forms of different seriousness: the
      mild form, characterized by diffused congestion, petechiae of gastric mucosa
      (scarlatina type rash) and by the presence of typical hyperemic and edematous
      polygonal areas, delimited by a thin snake skin reticulation. In the severe form,
      together with such aspects, mucosal erosion, red spots, or a diffused hemorrhagic
      gastropathy are added. The pre-eminent pathogenetic element of such lesions seems
      to be the pathological increase of the portal pressure. The role of the
      Helicobacter pylori (H. pylori) in the development of these alterations, in terms
      of prevalence of infection in hepatopathic subjects, is still controversial. The
      authors have performed a research to verify if the H. pylori infection is
      correlated to the presence and/or to the gravity of PHG. METHODS: One-hundred and
      nine patients, all suffering from hepatitis C virus (HCV)-correlated liver
      cirrhosis, with clinical and/or instrumental signs of portal hypertension have
      been analysed. RESULTS: The histological prevalence of the infection from H.
      pylori in our statistical analysis was of 23.8% (26/109 patients). CONCLUSIONS:
      The H. pylori infection appears to be not significant for the determination and
      the preservation of PHG.

PMID- 16971875
TI  - The combined endoscopic therapy (band ligation and sclerosis) in the eradication
      of the esophageal varices in the cirrhotic patient: our experience.
AB  - AIM: In course of liver cirrhosis, esophageal varices develop with an incidence
      of 8-15% a year, and they constitute a sign of seriousness of portal
      hypertension. The risk of bleeding is estimated around 10-15% a year. The varices
      hemorrhage causes a high rate of mortality (around 30-35% for every hemorrhagic
      event). It follows that it is necessary to plan prophylactic strategies for all
      the cirrhotic patients, who are at risk of bleeding, or have already bled.
      Medical treatment with beta-blockers is indicated in the prophylaxis of the first
      bleeding, while endoscopic treatment represents now the most effective
      methodology either in acute bleeding, or in the prophylaxis of hemorrhage
      relapses. The available endoscopic methodologies are the sclerosis or band
      ligation of esophageal varices. However, unanimous consent about the greater
      effectiveness of a methodology compared to the other one doesn't exist. As far as
      the varices eradication is concerned, the authors have done a research to verify
      if the combined techniques, proposed in various studies appeared in literature,
      can have some advantages, in comparison with the single methodologies. METHODS:
      Thirty-seven patients have been treated: 27 only with sclerosis and 10 with
      combined methodology (band-ligation followed by sclerosis of the small residual
      varices). RESULTS: The group treated with the combined therapy have shown a
      reduction in relapses and in the main side effects and a better patients'
      compliance. CONCLUSIONS: The combination of the two methodologies can have some
      advantages as for security, easiness of execution, reduction in complications, in
      varices relapse and, therefore, in the hemorrhagic relapses.

PMID- 16971876
TI  - Assessment of patients with acute mesenteric ischemia: multislice computed
      tomography signs and clinical performance in a group of patients with surgical
      correlation.
AB  - AIM: The aim of this paper was to describe signs and performance of multislice
      computed tomography (MSCT) in patients with acute mesenteric infarction (AMI).
      METHODS: MSCT examinations of 26 patients with AMI and of 34 patients with acute
      abdomen and surgical diagnosis excluding AMI were retrospectively analyzed. All
      studies were performed with arterial and portal venous phase scans, 2.5 mm
      thickness, 1.25 mm image interval. All abnormal findings at MSCT in patients with
      AMI were recor- ded. Patients with MSCT evidence of mesenteric artery occlusion
      or pneumatosis or venous gas or, alternatively, bowel thicken-ing associated with
      lack of wall enhancement or venous thrombosis or parenchimal infarction were
      considered to be affected by AMI. RESULTS: AMI was due to mesenteric artery
      thrombosis in 17 patients, mesenteric vein thrombosis in 7, and nonocclusive
      ischemia in 2. In 16/17 patients arterial thrombosis was visualized, in 7/7
      venous thrombosis was found. Portal or mesenteric vein gas was seen in 5% and
      pneumatosis in 38%; bowel wall thickening associated with other signs was found
      in 31%. Sensitivity and specificity were 92% and 100%, respectively. CONCLUSIONS:
      MSCT allows an accurate assessment of the mesenteric circulation and the bowel
      wall. This makes possible optimal visualization of signs of AMI resulting in a
      good clinical performance.

PMID- 16971877
TI  - Capsule endoscopy for the detection of bleeding Meckel's diverticulum. A case
      report.
AB  - The case of a 59-year-old man with a history of recurrent severe gastrointestinal
      bleeding due to Meckel's diverticulum is described. The diagnosis was achieved by
      means of capsule endoscopy. The histological examination revealed the presence of
      Meckel's diverticulum with ectopic gastric mucosa. The use of capsule endoscopy
      for the detection of Meckel's diverticulum is discussed.

PMID- 16971878
TI  - Endovascular obliteration of a ruptured right gastric artery aneurysm.
AB  - Aneurysms of the right gastric artery are extremely rare lesions. They constitute
      less than 0.001% of reported visceral artery aneurysms. A unique case of a
      ruptured right gastric artery aneurysm is presented. Angiographic diagnosis and
      endovascular treatment by right gastric artery embolization proved safe and
      efficacious, resulting in complete obliteration of the aneurysm with no adverse
      sequelae.

PMID- 16971879
TI  - Pneumatosis coli induced by acarbose administration for diabetes mellitus. Case
      report and literature review.
AB  - The authors report a case report of rare disease interesting the digestive tract
      and often associated to the other gastrointestinal pathologies and/or pulmonary
      diseases and can be also associated to not gastrointestinal conditions such as
      collagen-vascular disease, transplantation, AIDS, use of corticosteroid and
      chemotherapy; other causes can be iatrogenic such as traumatic gastrointestinal
      endoscopy (a mucoses biopsy, a polipectomy) or the assumption of lattulosio; in
      15-20% of cases the pneumatosis cystoides intestinalis is considered primitive.
      In the our case the Pneumatosis coli was associated to administration of
      acarbose; in international literature only four papers in the English language
      were reported. Our patient showed a strongly aspecific symptomatology and easily
      attributable in first line or to the pathology of base (diabetic patient) or to
      the assumption of the acarbose; from about 7-8 months she showed unexplained
      episodes of crampy abdominal pain, diarrhea with 3-4 defecations/die with
      semiliquid and normochromic stools, tenesmus and a not better specified loss of
      weight. The diagnosis was been performed by colonoscopy and confirmed by
      abdominal CT scan with water enema and histologically; we have used the
      traditional radiology only to exclude the involvement of other gastroenteric
      districts. The patient was been treated with O2-therapy associated to antibiotics
      treatment; the suspension of the causal factor, the acarbose, has been of not
      secondary importance; the complete resolution of disease was obtained after 15
      days of therapy.

PMID- 16971880
TI  - Mandibular distraction of the body and ramus.
AB  - With the ever increasing interest in the field of osteodistraction techniques,
      the mandible is certainly the most studied anatomical site, both experimentally
      and clinically. Currently, the methods of mandibular distraction can be
      classified by position (intra- or extraoral), by the direction of distraction and
      by the site of application (toothborn, boneborn or hybrid fixation). To guarantee
      good results from the osteodistraction procedure, it is fundamental to have an
      accurate preoperative plan considering the correct classification and evaluation
      of the patient combined with a valid project regarding the direction of the
      distraction vector. One of the most important aspects to consider is the
      orientation of the distractor, especially if the defect to be corrected is three
      dimensional. Regarding the correct planning of the operation, knowing the
      secondary effects of the distraction on the soft tissues, muscles and nerves, the
      temporomandibular joint and velopharyngeal functioning is of fundamental
      importance. It is worth considering particular situations in which
      osteodistraction is extremely helpful in maxillofacial surgery, for example in
      the construction of a neocondyle, in bone replacement during oncologic
      interventions, in obstructive sleep apnea correction and in hemi-mandibular
      reconstruction.

PMID- 16971881
TI  - Efficacy of physical therapy in the treatment of masticatory myofascial pain: a
      literature review.
AB  - The term temporomandibular disorders (TMD) is used to indicate a heterogeneous
      group of painful conditions involving masticatory apparatus and its related
      structures whose complicated etiology involves a number of diagnostic and
      taxonomical matters. The prevalence of TDM has remarkably increased in the last
      years, such that, at present, these clinical conditions represent the most
      frequent cause of orofacial pain in the general population: in particular, among
      these disorders, pathologies affecting masticatory muscles have a considerable
      clinical and epidemiological relevance. Due to the high prevalence of masticatory
      myofascial pain, as well as the taxonomical issue that emerges from literature
      data, the wide range of treatment modalities proposed for this condition seems to
      be justifiable. Among the various therapeutic solutions employed in the
      management of masticatory myofascial pain, it is interesting to focus on the
      efficacy of the different kinds of physical therapy. In fact, due to the
      difficulties related with the attempt to isolate a sole etiological factor, at
      the beginning should be carried out reversible and noninvasive interventions: in
      these terms, the use of physical therapy seems to be reasonable. The aim of the
      present paper is to provide a critical review of the literature about the use of
      physical therapy approaches in relieving pain symptoms that often accompany
      masticatory muscles disorders. This study seems to suggest that the employ of
      physical therapy could be useful in the treatment of myogenous TDM, even though
      further studies are needed to assess the efficacy of this tool.

PMID- 16971882
TI  - Arthroscopic laser surgery in temporomandibular functional joint disorders.
AB  - AIM: The authors present the 1-year results of combined use of arthroscopic lysis
      and lavage procedure, capsular stretch and holmium:yttrium-aluminium-garnet
      (Ho:YAG) laser techniques for the treatment of chronic closed lock of the
      temporomandibular joint. METHODS: Twelve joints were treated in 10 patients (9
      females and 1 male) affected by anterior disk displacement without reduction not
      responsive to conservative treatment. All the patients were studied with
      preoperative magnetic resonance immaging (MRI). Surgical procedures included
      lysis and lavage, capsular stretch and Ho:YAG laser techniques with anterior
      release, posterior scarification and debridment of cartilage surface. The
      individual outcome was evaluated with the clinical examination, a visual analogue
      scale (VAS) for pain and a questionnaire concerning mandibular functional
      impairment. Patients were followed-up for 1 year. RESULTS: One-year results show
      that 9 patients (success rate 90%) achieved improvement of mandibular function
      and reduction of pain. The clinical recordings at the 1-year follow-up indicated
      good outcomes. Nine patients could masticate a regular diet at 1-year follow-up.
      CONCLUSIONS: These findings seem to justify the use of Ho:YAG laser techniques
      together with the lysis and lavage procedure and capsular stretch for the
      treatment of chronic closed lock of the temporomandibular joint. These
      arthroscopic procedures represent the first choice and an effective approach in
      the surgical treatment of this condition.

PMID- 16971883
TI  - Internal adaptation of fixed prosthodontics at shoulder preparation level
      evaluated by horizontal sections.
AB  - AIM: The precision of fixed prosthodontic restorations is fundamental for
      clinical success: well-fitting crowns reduce the risk of recurrent caries and
      periodontal disease. The aim of this study is to evaluate the internal fit of
      fixed prosthodontics at the shoulder preparation level by examining horizontal
      sections. METHODS: Twenty-four extracted teeth were resin-embedded and prepared
      on the platform of an iso-parallelometer with a 90 degrees shoulder with a
      rounded internal angle. Auro Galva Crown (AGC) copings were cemented in place.
      The preparations were observed by 3 different assessors at 8 points, first
      externally and then internally at 2 levels by grinding the specimen perpendicular
      to the long axis at 0.5 mm and at 0.2 mm from the margin of the preparation. A
      correction factor was calculated to derive real values from measured values. The
      results were analyzed using a linear regression with robust standard errors,
      accounting for within-subject correlation introduced by multiple measurements.
      Shrout-Fleiss Intraclass Correlation Coefficient (ICC) for Inter-Rater
      Reliability were calculated at each stage. RESULTS: Internal measurements at 0.5
      and 0.2 mm from the margin provided data similar to the external margin data.
      Average inter-assessor differences were in the range of 2 mm. ICC ranged from
      0.93 for the 0.5 mm level to 0.97 for the external level. CONCLUSIONS: External
      measurements effectively predict the internal precision at the shoulder level.
      Horizontal perimarginal sections allow the fit to be studied through the
      evaluation of a great number of points. Traditional vertical sections for the
      evaluation of internal fit enable only a few points to be observed. This internal
      observation method may be suitable for testing new materials.

PMID- 16971884
TI  - Evaluation of Milan University Dental Students' knowledge of health and hygiene
      risks related to clinical work.
AB  - AIM: Several different subjects in the Degree Course in Dentistry and
      Prosthodontics, including Hygiene, are of fundamental importance to understand
      and prevent hygiene/ health risks in the dental field. The aim of this
      investigation is to evaluate the knowledge acquired by students during the Degree
      Course in Dentistry. METHODS: A questionnaire was distributed to 121 students of
      the Degree Course in Dentistry and Prosthodontics at Milan University; the
      questionnaire, drawn up by the Working Group SItI ''Hygiene in Dentistry'' was
      structured in 3 parts: personal data; transmission of infectious diseases in
      dentistry; measures to control and prevent cross-infection. RESULTS: The students
      were all aware of the health/hygiene risks in dentistry; they knew the principal
      transmissible infectious diseases (while confusing actual risk of transmission
      with disease's fears) and the procedures at highest risk of cross-infection for
      patients and dental professionals; they correctly determined the highest-risk
      categories of patients and the individual protection devices to be used in dental
      practice. However, they knew little about their own vaccination status; a low
      percentage of students answered correctly on which environmental matrices can be
      contaminated or the more technical questions on disinfection and sterilisation
      procedures for the instruments employed. CONCLUSIONS: The students' replies show
      they possess a fair theoretical knowledge of transmission risks; however, some
      gaps exist above all in the practical application of this knowledge, and it
      appears clear that these should be addressed in detail, possibly with the help of
      a specific tutor providing support during normal clinical work in the last year
      of the course.

PMID- 16971885
TI  - Oral metastasis of ciliary body melanoma. A case report.
AB  - Metastases of melanoma rarely occur in the oral cavity, and very few reports have
      been published. They are chiefly localized in the tonsil, tongue and lip,
      regardless of the primary site of the neoplasm. A 76-year-old woman presented a
      brownish berry-shaped floating neoformation at the upper lip, for which she was
      hospitalized at the Maxillofacial Surgery Unit, Italian Stomatologic Institute,
      Milan. Medical history revealed that 6 years previously, in 1998, she underwent
      enucleation of the right eye due to the presence of a melanoma of the ciliary
      body. The labial neoplasm was removed and at histological examination it was
      found to be a spindle cell melanoma with numerous melanophages containing
      granules of melanin. Both the spindle cells and the melanophages were strongly
      positive for HMB-45 and for S-100. Thus, the presence of melanic neoplasia at an
      unusual site together with the medical history of melanoma at the ciliary body,
      removed 6 years previously, indicated a diagnosis of labial metastasis of
      melanoma of the ciliary body and the patient was therefore transferred to the
      Oncology Unit for appropriate treatment.

PMID- 16971886
TI  - State-specific prevalence of obesity among adults--United States, 2005.
AB  - Obesity, one of the 10 leading U.S. health indicators, is associated with
      increased risk for hypertension, dyslipidemia, type 2 diabetes, coronary heart
      disease, stroke, and certain cancers. A Healthy People 2010 objective is to
      reduce to 15% the prevalence of obesity among adults in the United States
      (objective 19-2). Both national-level data from the National Health and Nutrition
      Examination Survey (NHANES) and state-level data from the Behavioral Risk Factor
      Surveillance System (BRFSS) indicate that the prevalence of obesity among adults
      continued to increase during the past decade. In 2003, one study estimated that
      state-specific, obesity-attributable medical expenditures ranged from $87 million
      in Wyoming to $7.7 billion in California. To assess the prevalence of obesity
      among adults by state and demographic characteristics since 1995, data were
      analyzed from the 1995, 2000, and 2005 BRFSS surveys. The results of these
      analyses indicated that 23.9% of U.S. adults were obese in 2005, and the
      prevalence of obesity increased during 1995-2005 in all states. To reverse this
      trend, a sustained and effective public health response is needed, including
      surveillance, research, policies, and programs directed at improving
      environmental factors, increasing awareness, and changing behaviors to increase
      physical activity and decrease calorie intake.

PMID- 16971887
TI  - National, state, and urban area vaccination coverage among children aged 19-35
      months--United States, 2005.
AB  - The National Immunization Survey (NIS) provides vaccination coverage estimates
      among children aged 19-35 months for each of the 50 states and selected urban
      areas. Findings from the 2005 NIS include nationwide increases in coverage with
      >/=3 and >/=4 doses of pneumococcal conjugate vaccine (PCV) and continued high
      levels of coverage for the other recommended vaccines and vaccine series. In
      addition, no racial/ethnic disparities in coverage estimates were observed in the
      4:3:1:3:3:1 vaccine series, the recommended series for children aged 19-35 months
      that includes DTP/DT/DTaP; poliovirus vaccine; measles, mumps, and rubella
      vaccine (MMR); Haemophilus influenzae type b vaccine; hepatitis B vaccine; and
      varicella vaccine. An important accomplishment indicated by the 2005 NIS data is
      the achievement of <50% coverage for the full series of PCV (>/=4 doses) and <80%
      coverage for >/=3 doses within 5 years after being added to the U.S.-recommended
      childhood immunization schedule in 2000. This occurred despite shortages of this
      vaccine during 2001-2004, which might have affected accessibility to PCV.

PMID- 16971888
TI  - Public health response to varicella outbreaks--United States, 2003-2004.
AB  - Since introduction of varicella vaccine in 1995, incidence of varicella has
      decreased as vaccination coverage has increased. Nevertheless, varicella
      outbreaks continue to occur, even among populations with high vaccination
      coverage. Although varicella typically is mild, the outbreaks can last for
      several months and be challenging and costly for health departments to control.
      In 2005, CDC conducted a national survey to determine the distribution and extent
      of reported varicella outbreaks during 2003-2004 and the public health response.
      This report summarizes the results of that survey, which indicated that varicella
      outbreaks are still common and that health jurisdictions are responding to these
      outbreaks, although they have varying definitions and guidelines for varicella
      outbreak management.

PMID- 16971889
TI  - West Nile virus activity--United States, January 1-September 12, 2006.
AB  - This report summarizes West Nile virus (WNV) surveillance data reported to CDC
      through ArboNET as of 3 a.m. Mountain Daylight Time, September 12, 2006. A total
      of 36 states and the District of Columbia had reported 1,634 cases of human WNV
      illness to CDC. A total of 921 (57%) cases for which such data were available
      occurred in males; median age of patients was 51 years (range: 3 months-95
      years). Dates of illness onset ranged from January 6 to September 10; a total of
      52 cases were fatal.

PMID- 16971890
TI  - Enterovirus surveillance--United States, 1970-2005.
AB  - PROBLEM: Enteroviruses are common human viruses associated with various clinical
      syndromes, from minor febrile illness to severe, potentially fatal conditions
      (e.g., aseptic meningitis, paralysis, myocarditis, and neonatal enteroviral
      sepsis). Multiple enterovirus serotypes exist. Individual serotypes have
      different temporal patterns of circulation and often are associated with
      different clinical manifestations. Changes in circulating serotypes might be
      accompanied by large-scale outbreaks. REPORTING PERIOD COVERED: 1970-2005.
      DESCRIPTION OF SURVEILLANCE SYSTEM: The National Enterovirus Surveillance System
      (NESS) is a voluntary, passive surveillance system that has monitored trends in
      circulating enteroviruses since 1961. Enterovirus detections by serotype with
      specimen type, collection date, and demographic information are reported monthly
      by participating laboratories to CDC, which summarizes the data and disseminates
      the results. For this analysis, the available data set for 1970-1982 included
      only information on serotype and state for each report; complete records were
      available for 1983-2005. RESULTS: During 1970-2005, a total of 52,812 enterovirus
      detections were reported to NESS (29,772 of them during 1983-2005). Laboratory
      participation and the numbers of reports declined throughout the 1990s, but they
      increased again after 2000. The 15 most commonly reported enteroviruses accounted
      for 83.5% of reports with known serotype, and the five most commonly reported
      serotypes (echoviruses [E] 9, 11, 30, and 6, and coxsackievirus B5) accounted for
      48.1%. Predominant serotypes and ranking of individual enteroviruses changed over
      time. Long-term circulation patterns for individual serotypes varied but were
      consistent with epidemic (e.g., E9, E13, E30, and coxsackievirus B5) or endemic
      patterns (e.g., coxsackieviruses A9, B2, B4, and enterovirus 71). Children aged
      <1 year accounted for 44.2% of reports with known age. Male predominance was
      present among patients aged <20 years, but not among those aged >/=20 years
      (male/female ratio: 1.4 and 0.9, respectively). Enterovirus detections had
      prominent summer-fall seasonality, with June-October accounting for 77.9% of
      reports with known month of specimen collection. Cerebrospinal fluid was the most
      common specimen type, followed by respiratory and fecal specimens (49.8%, 26.9%,
      and 13.6%, respectively). Death was reported for 3.3% of detections with known
      outcome. Infections with coxsackievirus B4 (odds ratio [OR] = 3.3; 95% confidence
      interval [CI] = 1.7-6.0), and human parechovirus 1 (formerly E22) (OR = 3.7; CI =
      1.7-7.6) were associated with higher risk for death, and infections with E9 were
      associated with lower risk for death (OR = 0.1; CI = 0-0.4) than infections with
      other enteroviruses. INTERPRETATION: NESS data allowed identification and
      description of a core group of consistently circulating enteroviruses that
      probably determine the disease burden associated with enterovirus infections.
      These data also are helpful in guiding outbreak investigations and identifying
      targets for development of diagnostic assays and antivirals. Efforts to update
      the reporting system initiated in the early 2000s (i.e., simplification of
      reporting forms and transition to electronic reporting) resulted in a substantial
      increase in reporting compared with the late 1990s. PUBLIC HEALTH ACTION: Efforts
      to increase laboratory participation in NESS should continue to allow for more
      complete and accurate surveillance for enteroviruses. Further improvement in the
      timeliness of feedback through the development of a NESS website to allow access
      to historic data and to the information on circulating serotypes can provide
      additional incentives to public health laboratories to participate in NESS.

PMID- 16971891
TI  - A novel mutation of PAX3 in a Chinese family with Waardenburg syndrome.
AB  - PURPOSE: The molecular characterization of 34 members of a Chinese family, with
      22 members in four generations, affected with Waardenburg syndrome (WS1).
      METHODS: A detailed family history and clinical data were collected. A genome
      wide scan by two-point linkage analysis using more than 400 microsatellite
      markers in combination with haplotype analysis was performed. Mutation screening
      was carried out in the candidate gene by sequencing of amplified products.
      RESULTS: A maximum two-point lod score of 6.53 at theta = 0.00 was obtained with
      marker D2S2248. Haplotype analysis placed the WS1 locus to a 45.74 cM region
      between D2S117 and D2S206, in close proximity to the PAX3 gene on chromosome
      2q35. Mutation screening in PAX3 identified a 701T > C mutation which converted a
      highly conserved Leu to Pro. This nucleotide alteration was neither seen in
      unaffected members of the family nor found in 50 unrelated control subjects.
      CONCLUSIONS: The present study identified a novel 701T > C mutation in PAX3. The
      mutation observed in this family highlights the phenotypic heterogeneity of the
      disorder.

PMID- 16971892
TI  - Juvenile bilateral lens dislocation and glaucoma associated with a novel mutation
      in the fibrillin 1 gene.
AB  - PURPOSE: To describe the clinical, ocular, and genetic findings in multiple
      members of a family with early-onset and bilateral lens dislocation, clinical
      corneal guttae, and glaucoma. METHODS: All family members underwent complete
      physical and ophthalmic examinations. After informed consent was given, DNA was
      obtained from eleven family members, eight of whom were affected. Three
      polymorphic markers near the fibrillin 1 (FBN1) locus were genotyped and the
      results analyzed using the VITESSE program. Amplification of the 65 exons and
      flanking intronic sequences of FBN1 was performed using polymerase chain reaction
      (PCR), followed by conformation sensitive gel electrophoresis (CSGE). Then, all
      fragments with mobility variations were sequenced. RESULTS: Pedigree analysis
      revealed a three generation family with eight of eleven individuals affected by
      early onset lens dislocation, high myopia, typical facies, frontal bossing,
      flexion contractures, proximal interphalangeal (PIP) joint thickening, clinical
      corneal guttae, and glaucoma. Genetic linkage analysis using polymorphic markers
      near FBN1 demonstrated an LOD score of 1.78 (maximum possible LOD score 1.78).
      Conformation sequence gel electrophoresis analysis suggested a sequence variation
      in exon 3. Sequencing revealed a C965G substitution, resulting in an S322C coding
      change. This sequence variant segregated with affection status and was not
      identified in 154 control chromosomes. CONCLUSIONS: This syndrome is consistent
      with a novel mutation in the FBN1 gene. FBN1 mutations have been previously
      described as causative for Marfan syndrome. The early-onset of complete lens
      dislocation, progressive corneal guttae, and glaucoma is unusual for Marfan
      syndrome. This study expands the Marfan phenotype and demonstrates a possible
      link between guttae, glaucoma, and fibrillin 1 disorders.

PMID- 16971893
TI  - Investigations on the association between normal tension glaucoma and single
      nucleotide polymorphisms of the endothelin-1 and endothelin receptor genes.
AB  - PURPOSE: In normal tension glaucoma (NTG), intraocular pressure is within normal
      the range; thus, some mechanism other than increased pressure contributes to the
      optic neuropathy. Endothelin may be an important contributor to the development
      of the optic neuropathy characteristic of glaucoma. We investigated whether
      polymorphisms of the endothelin-1, endothelin receptor type A, and endothelin
      receptor type B genes were associated with NTG. METHODS: Sixty-seven Korean NTG
      patients and 100 healthy Korean subjects were enrolled. DNA from peripheral blood
      leukocytes was extracted and genotype distributions of six polymorphisms in genes
      encoding endothelin-1 (EDN1:c.-131dupA, EDN1:c.594G > T), endothelin receptor
      type A (EDNRA:c.-231G > A, EDNRA:c.*70C > G, EDNRA:c.*1222C > T), and endothelin
      receptor type B (EDNRB:c.831A > G) were determined. Genotype and allele
      distributions were compared between patients and controls. In NTG subjects,
      untreated baseline intraocular pressure and age at the time of diagnosis, as well
      as the mean deviation and pattern standard deviation values of automated static
      perimetry were examined for an association with these genetic polymorphisms.
      RESULTS: The polymorphism of EDNRA:c.*1222C > T was significantly associated with
      NTG (p = 0.028, OR = 3.33, 95% CI 1.05-10.24). In addition, the AA genotype of
      the EDNRA:c.-231G > A polymorphism was associated with a lower baseline
      intraocular pressure than in the GG+GA genotype group (14.0 +/- 2.8 mm Hg versus
      16.2 +/- 2.3 mm Hg, p = 0.047). No polymorphism was associated with visual field
      parameters. CONCLUSIONS: A polymorphism of the endothelin receptor type A gene is
      associated with NTG.

PMID- 16971895
TI  - The congenital "ant-egg" cataract phenotype is caused by a missense mutation in
      connexin46.
AB  - PURPOSE: "Ant-egg" cataract is a rare, distinct variety of congenital/infantile
      cataract that was reported in a large Danish family in 1967. This cataract
      phenotype is characterized by ant-egg-like bodies embedded in the lens in a
      laminar configuration and is inherited as an autosomal dominant trait. We
      retrieved the family and performed linkage analysis to determine the disease
      locus and identify the mutated gene. METHODS: The family (CC00103) was identified
      in a National Register of Hereditary Eye Diseases and updated based on The Danish
      Civil Register System. Genome wide linkage analysis and haplotyping using STS
      marker systems were carried out to achieve a LOD score above 3. The disease
      causing candidate gene was sequenced and the mutation was identified and verified
      by restriction enzyme digestion of genomic DNA from all individuals in family
      CC00103 and 60 healthy controls. RESULTS: Linkage analysis resulted in a LOD
      score of 3.91 for marker D13S1275 located close to the known cataract gene GJA3.
      A novel missense mutation c.32T > C (L11S), was found by sequencing DNA from two
      affected members. The mutation was present in all affected individuals and was
      neither found in unaffected family members nor in 60 healthy individuals by
      restriction enzyme digests. CONCLUSIONS: The congenital "ant-egg" cataract
      phenotype is caused by a L11S mutation in connexin46 (Cx46) located in the signal
      peptide domain. Further studies are needed to unravel the mechanism leading to
      the formation of the "ant-eggs".

PMID- 16971894
TI  - In vitro and in vivo characterization of iris pigment epithelial cells cultured
      on amniotic membranes.
AB  - PURPOSE: To determine whether human amniotic membranes (AMs) can induce human and
      rat iris pigment epithelial (IPE) cells grown on them to develop characteristics
      of RPE cells in situ better than IPE cells grown on plastic plates, and to
      determine whether subretinal transplantation of IPE cell sheets grown on AMs can
      protect photoreceptor cells in dystrophic Royal College of Surgeons (RCS) rats.
      METHODS: IPE cells from humans and Long-Evans rats were cultured on the basement
      membrane side of dispase-treated AMs. Two weeks after seeding, ultrastructural
      changes were evaluated by transmission electron microscopy, and the level of
      expression of several genes present in differentiated retinal pigment epithelial
      (RPE) cells was determined by real time PCR and western blotting. IPE cell sheets
      cultured on AMs were transplanted into the subretinal space of 4-week-old RCS
      rats, and eyes were analyzed histologically 12 weeks after grafting. RESULTS: IPE
      cells cultured on AMs showed ultrastructural features like intercellular
      junctions, similar to RPE cells in situ. IPE cells grown on AMs had a greater
      upregulation in the expression of genes important for the function of
      differentiated RPE cells (e.g., pigment epithelium-derived factor [PEDF], RPE65,
      bestrophin, VEGF, and BDNF) than IPE cells grown on plastic plates. The number of
      photoreceptors present in RCS rats after subretinal transplantation of IPE cell
      sheets grown on AMs was significantly higher than that of sham injected rats and
      rats receiving transplantation of AMs without IPE cells. CONCLUSIONS: The more
      advanced degree of differentiation of IPE cells grown on AMs indicates that AMs
      are a better substrate to culture IPE cells than plastic plates. This was
      supported by the greater protection of photoreceptors of RCS rats when IPE cell
      sheets cultured on AMs were transplanted in the subretinal space.

PMID- 16971896
TI  - Serotonin receptor subtype mRNA expression in human ocular tissues, determined by
      RT-PCR.
AB  - PURPOSE: To determine the relative density and tissue localization of mRNAs for
      serotonin (5-hydroxytryptamine; 5HT) receptor subtypes in human ocular tissues
      and correlate with their possible functions in the eye. METHODS: Total RNA was
      extracted from human ocular tissues samples from multiple donors and transcribed
      into cDNA. An optimized reverse transcriptase polymerase chain reaction (RT-PCR)
      procedure was then used to amplify the signals using primers designed against
      human 5HT receptor cDNAs. The PCR products were analyzed by gel electrophoresis
      and confirmed by endonuclease digestion. RESULTS: Variable amounts of total RNA
      were extracted from different tissues with the least amount from ciliary
      epithelium and most amount from retina. 5HT2 receptor subtype mRNAs were the most
      abundant with 5HT2A and 5HT2B being the most predominant in the retina, ciliary
      body, ciliary epithelium, choroid, conjunctiva, and iris. Ciliary body, choroid,
      and conjunctiva were most enriched in 5HT3 receptor mRNA, with relatively lower
      levels in the iris. 5HT4 receptor mRNA was most enriched in the retina, ciliary
      body, choroid, conjunctiva, and somewhat detectable in the iris. 5HT5 receptor
      mRNA was abundant in the retina, ciliary body, and iris. 5HT6 receptor mRNA was
      the least abundant of all subtypes studied and could only be detected in the
      iris. 5HT7 receptor mRNA was enriched in the ciliary body, choroid, conjunctiva,
      and iris, with much lower levels in the retina and ciliary epithelium. Optic
      nerve tissue of 1-2 donors exhibited the presence of 5HT2B, 5HT5, and 5HT7
      receptor mRNAs. Data for human trabecular meshwork cells indicated a high density
      of mRNAs for 5HT2A and 5HT2B, with much lower levels of 5HT2C, 5HT5, and 5HT7
      receptor mRNAs. CONCLUSIONS: Human ocular tissues differentially expressed mRNAs
      for the various 5HT receptor subtypes. These studies suggest a diverse range of
      possible physiological and pharmacological functions of 5HT receptors in these
      human ocular tissues.

PMID- 16971897
TI  - Molecular mechanisms of muscular dystrophies: old and new players.
AB  - The study of the muscle cell in the muscular dystrophies (MDs) has shown that
      mutant proteins result in perturbations of many cellular components. MDs have
      been associated with mutations in structural proteins, signalling molecules and
      enzymes as well as mutations that result in aberrant processing of mRNA or
      alterations in post-translational modifications of proteins. These findings have
      not only revealed important insights for cell biologists, but have also provided
      unexpected and exciting new approaches for therapy.

PMID- 16971898
TI  - Scopolamine induces disruption of latent inhibition which is prevented by
      antipsychotic drugs and an acetylcholinesterase inhibitor.
AB  - The fact that muscarinic antagonists may evoke a psychotic state ('antimuscarinic
      psychosis'), along with findings of cholinergic alterations in schizophrenia,
      have kindled an interest in the involvement of the cholinergic system in this
      disorder. Latent inhibition (LI) is a cross-species phenomenon manifested as a
      poorer conditioning of a stimulus seen when the stage of conditioning is preceded
      by a stage of repeated nonreinforced pre-exposure to that stimulus, and is
      considered to index the capacity to ignore irrelevant stimuli. Amphetamine
      induced LI disruption and its reversal by antipsychotic drugs (APDs) is a well
      established model of positive symptoms of schizophrenia. Here, we tested whether
      the muscarinic antagonist scopolamine would disrupt LI and whether such
      disruption would be reversed by APDs and by the acetylcholinesterase inhibitor
      physostigmine. The results showed that scopolamine at doses of 0.15 and 0.5 mg/kg
      disrupted LI, and that this effect was due to the action of the drug in the pre
      exposure stage, suggesting a role of muscarinic transmission in attentional
      processes underlying LI. Both the typical and the atypical APDs, haloperidol and
      clozapine, reversed scopolamine-induced LI disruption when given in conditioning
      or in both stages, but not in pre-exposure, indicating that the mechanism of
      antipsychotic action in this model is independent of the mechanism of action of
      the propsychotic drug. Scopolamine-induced LI disruption was reversed by
      physostigmine (0.05 and 0.15 mg/kg), which was ineffective in reversing
      amphetamine-induced LI disruption, pointing to distinct mechanisms underlying LI
      disruption by these two propsychotic drugs. The latter was further supported by
      the finding that unlike amphetamine, the LI-disrupting doses of scopolamine did
      not affect activity levels. We propose scopolamine-induced LI disruption as a
      model of cholinergic-related positive symptoms in schizophrenia.

PMID- 16971899
TI  - A single dose of the selective serotonin reuptake inhibitor citalopram
      exacerbates anxiety in humans: a fear-potentiated startle study.
AB  - Serotonin reuptake inhibitors may increase symptoms of anxiety immediately
      following treatment initiation. The present study examined whether acute
      citalopram increased fear-potentiated startle to predictable and/or unpredictable
      shocks in healthy subjects. Eighteen healthy subjects each received two
      treatments, placebo and 20 mg citalopram in a crossover design. Participants were
      exposed to three conditions including one in which predictable aversive shocks
      were signaled by a cue, a second in which unpredictable shocks were anticipated,
      and a third in which no shocks were administered. Changes in aversive states were
      investigated using acoustic startle stimuli. Citalopram did not affect baseline
      startle. However, the phasic startle potentiation to the threat cue in the
      predictable condition was robustly increased by acute citalopram. The sustained
      startle potentiation in the unpredictable conditions was also increased by
      citalopram, but only when the drug was given during the first session. These
      results indicate that a single dose of citalopram is not anxiogenic in itself,
      but can exacerbate the expression of fear and anxiety.

PMID- 16971900
TI  - Increased occupancy of dopamine receptors in human striatum during cue-elicited
      cocaine craving.
AB  - In all, 19 research subjects, with current histories of frequent cocaine use,
      were exposed to cocaine-related cues to elicit drug craving. We measured the
      change of occupancy of dopamine at D2-like receptors with positron emission
      tomography (PET) and inferred a change of intrasynaptic dopamine (endogenous
      dopamine release), based on the displacement of radiotracer [(11)C]raclopride.
      Receptor occupancy by dopamine increased significantly in putamen of participants
      who reported cue-elicited craving compared to those who did not. Further, the
      intensity of craving was positively correlated with the increase in dopamine
      receptor occupancy in the putamen. These results provide direct evidence that
      occupancy of dopamine receptors in human dorsal striatum increased in proportion
      to subjective craving, presumably because of increased release of intrasynaptic
      dopamine.

PMID- 16971906
TI  - Flickers of consciousness.

PMID- 16971907
TI  - Whistleblowers in peril.

PMID- 16971901
TI  - Archaeology: progress and pitfalls in radiocarbon dating.

PMID- 16971908
TI  - Resisting terrorism.

PMID- 16971911
TI  - Neutrinos make a splash in Italy.

PMID- 16971912
TI  - Warning flag for ethics boards.

PMID- 16971913
TI  - Biomedical research gets a fresh twist down on the farm.

PMID- 16971914
TI  - Journey to the birth of the Universe.

PMID- 16971915
TI  - Extreme TB strain threatens HIV victims worldwide.

PMID- 16971916
TI  - Snapshot: women at work.

PMID- 16971917
TI  - 'Vegetative' patient shows signs of conscious thought.

PMID- 16971920
TI  - Nanotech's big issue.

PMID- 16971921
TI  - Ornithology: digging for dodo.

PMID- 16971922
TI  - Climate change: a cosmic connection.

PMID- 16971923
TI  - Science networks spread throughout the Arab world.

PMID- 16971924
TI  - Biochar and biofuels for a brighter future.

PMID- 16971925
TI  - Biochar trials aim to enrich soil for smallholders.

PMID- 16971926
TI  - Investigator-initiated trials are more impartial.

PMID- 16971932
TI  - Crystallography: solid oxygen takes shape.

PMID- 16971933
TI  - Astronomy: dawn after the dark age.

PMID- 16971934
TI  - Cancer biology: can less be more for p53?

PMID- 16971935
TI  - Quantum physics: observing and the observed.

PMID- 16971936
TI  - Structural biology: the ins and outs of drug transport.

PMID- 16971938
TI  - Obituary: James A. Van Allen (1914-2006).

PMID- 16971939
TI  - Entomology: to catch a bee.

PMID- 16971940
TI  - Tumour biology: Policing of oncogene activity by p53.

PMID- 16971941
TI  - Variations in solar luminosity and their effect on the Earth's climate.
AB  - Variations in the Sun's total energy output (luminosity) are caused by changing
      dark (sunspot) and bright structures on the solar disk during the 11-year sunspot
      cycle. The variations measured from spacecraft since 1978 are too small to have
      contributed appreciably to accelerated global warming over the past 30 years. In
      this Review, we show that detailed analysis of these small output variations has
      greatly advanced our understanding of solar luminosity change, and this new
      understanding indicates that brightening of the Sun is unlikely to have had a
      significant influence on global warming since the seventeenth century. Additional
      climate forcing by changes in the Sun's output of ultraviolet light, and of
      magnetized plasmas, cannot be ruled out. The suggested mechanisms are, however,
      too complex to evaluate meaningfully at present.

PMID- 16971942
TI  - A galaxy at a redshift z = 6.96.
AB  - When galaxy formation started in the history of the Universe remains unclear.
      Studies of the cosmic microwave background indicate that the Universe, after
      initial cooling (following the Big Bang), was reheated and reionized by hot stars
      in newborn galaxies at a redshift in the range 6 < z < 14 (ref. 1). Though
      several candidate galaxies at redshift z > 7 have been identified
      photometrically, galaxies with spectroscopically confirmed redshifts have been
      confined to z < 6.6 (refs 4-8). Here we report a spectroscopic redshift of z =
      6.96 (corresponding to just 750 Myr after the Big Bang) for a galaxy whose
      spectrum clearly shows Lyman-alpha emission at 9,682 A, indicating active star
      formation at a rate of approximately 10M(o) yr(-1), where M(o) is the mass of the
      Sun. This demonstrates that galaxy formation was under way when the Universe was
      only approximately 6 per cent of its present age. The number density of galaxies
      at z approximately 7 seems to be only 18-36 per cent of the density at z = 6.6.

PMID- 16971943
TI  - Rapid evolution of the most luminous galaxies during the first 900 million years.
AB  - The first 900 million years (Myr) to redshift z approximately 6 (the first seven
      per cent of the age of the Universe) remains largely unexplored for the formation
      of galaxies. Large samples of galaxies have been found at z approximately 6 (refs
      1-4) but detections at earlier times are uncertain and unreliable. It is not at
      all clear how galaxies built up from the first stars when the Universe was about
      300 Myr old (z approximately 12-15) to z approximately 6, just 600 Myr later.
      Here we report the results of a search for galaxies at z approximately 7-8, about
      700 Myr after the Big Bang, using the deepest near-infrared and optical images
      ever taken. Under conservative selection criteria we find only one candidate
      galaxy at z approximately 7-8, where ten would be expected if there were no
      evolution in the galaxy population between z approximately 7-8 and z
      approximately 6. Using less conservative criteria, there are four candidates,
      where 17 would be expected with no evolution. This demonstrates that very
      luminous galaxies are quite rare 700 Myr after the Big Bang. The simplest
      explanation is that the Universe is just too young to have built up many luminous
      galaxies at z approximately 7-8 by the hierarchical merging of small galaxies.

PMID- 16971944
TI  - Cooling a nanomechanical resonator with quantum back-action.
AB  - Quantum mechanics demands that the act of measurement must affect the measured
      object. When a linear amplifier is used to continuously monitor the position of
      an object, the Heisenberg uncertainty relationship requires that the object be
      driven by force impulses, called back-action. Here we measure the back-action of
      a superconducting single-electron transistor (SSET) on a radio-frequency
      nanomechanical resonator. The conductance of the SSET, which is capacitively
      coupled to the resonator, provides a sensitive probe of the latter's position;
      back-action effects manifest themselves as an effective thermal bath, the
      properties of which depend sensitively on SSET bias conditions. Surprisingly,
      when the SSET is biased near a transport resonance, we observe cooling of the
      nanomechanical mode from 550 mK to 300 mK--an effect that is analogous to laser
      cooling in atomic physics. Our measurements have implications for nanomechanical
      readout of quantum information devices and the limits of ultrasensitive force
      microscopy (such as single-nuclear-spin magnetic resonance force microscopy).
      Furthermore, we anticipate the use of these back-action effects to prepare
      ultracold and quantum states of mechanical structures, which would not be
      accessible with existing technology.

PMID- 16971945
TI  - Oscillatory dependence of current-driven magnetic domain wall motion on current
      pulse length.
AB  - Magnetic domain walls, in which the magnetization direction varies continuously
      from one direction to another, have long been objects of considerable interest.
      New concepts for devices based on such domain walls are made possible by the
      direct manipulation of the walls using spin-polarized electrical current through
      the phenomenon of spin momentum transfer. Most experiments to date have
      considered the current-driven motion of domain walls under quasi-static
      conditions, whereas for technological applications, the walls must be moved on
      much shorter timescales. Here we show that the motion of domain walls under
      nanosecond-long current pulses is surprisingly sensitive to the pulse length. In
      particular, we find that the probability of dislodging a domain wall, confined to
      a pinning site in a permalloy nanowire, oscillates with the length of the current
      pulse, with a period of just a few nanoseconds. Using an analytical model and
      micromagnetic simulations, we show that this behaviour is connected to a current
      induced oscillatory motion of the domain wall. The period is determined by the
      wall's mass and the slope of the confining potential. When the current is turned
      off during phases of the domain wall motion when it has enough momentum, the
      domain wall is driven out of the confining potential in the opposite direction to
      the flow of spin angular momentum. This dynamic amplification effect could be
      exploited in magnetic nanodevices based on domain wall motion.

PMID- 16971946
TI  - Observation of an O8 molecular lattice in the epsilon phase of solid oxygen.
AB  - Of the simple diatomic molecules, oxygen is the only one to carry a magnetic
      moment. This makes solid oxygen particularly interesting: it is considered a
      'spin-controlled' crystal that displays unusual magnetic order. At very high
      pressures, solid oxygen changes from an insulating to a metallic state; at very
      low temperatures, it even transforms to a superconducting state. Structural
      investigations of solid oxygen began in the 1920s and at present, six distinct
      crystallographic phases are established unambiguously. Of these, the epsilon
      phase of solid oxygen is particularly intriguing: it exhibits a dark-red colour,
      very strong infrared absorption, and a magnetic collapse. It is also stable over
      a very large pressure domain and has been the subject of numerous X-ray
      diffraction, spectroscopic and theoretical studies. But although epsilon-oxygen
      has been shown to have a monoclinic C2/m symmetry and its infrared absorption
      behaviour attributed to the association of oxygen molecules into larger units,
      its exact structure remains unknown. Here we use single-crystal X-ray diffraction
      data collected between 13 and 18 GPa to determine the structure of epsilon
      oxygen. We find that epsilon-oxygen is characterized by the association of four
      O2 molecules into a rhombohedral molecular unit, held together by what are
      probably weak chemical bonds. This structure is consistent with existing
      spectroscopic data, and further validated by the observation of a newly predicted
      Raman stretching mode.

PMID- 16971947
TI  - Land-atmosphere coupling and climate change in Europe.
AB  - Increasing greenhouse gas concentrations are expected to enhance the interannual
      variability of summer climate in Europe and other mid-latitude regions,
      potentially causing more frequent heatwaves. Climate models consistently predict
      an increase in the variability of summer temperatures in these areas, but the
      underlying mechanisms responsible for this increase remain uncertain. Here we
      explore these mechanisms using regional simulations of recent and future climatic
      conditions with and without land-atmosphere interactions. Our results indicate
      that the increase in summer temperature variability predicted in central and
      eastern Europe is mainly due to feedbacks between the land surface and the
      atmosphere. Furthermore, they suggest that land-atmosphere interactions increase
      climate variability in this region because climatic regimes in Europe shift
      northwards in response to increasing greenhouse gas concentrations, creating a
      new transitional climate zone with strong land-atmosphere coupling in central and
      eastern Europe. These findings emphasize the importance of soil-moisture
      temperature feedbacks (in addition to soil-moisture-precipitation feedbacks) in
      influencing summer climate variability and the potential migration of climate
      zones with strong land-atmosphere coupling as a consequence of global warming.
      This highlights the crucial role of land-atmosphere interactions in future
      climate change.

PMID- 16971948
TI  - An intron with a constitutive transport element is retained in a Tap messenger
      RNA.
AB  - Alternative splicing is a key factor contributing to genetic diversity and
      evolution. Intron retention, one form of alternative splicing, is common in
      plants but rare in higher eukaryotes, because messenger RNAs with retained
      introns are subject to cellular restriction at the level of cytoplasmic export
      and expression. Often, retention of internal introns restricts the export of
      these mRNAs and makes them the targets for degradation by the cellular nonsense
      mediated decay machinery if they contain premature stop codons. In fact, many of
      the database entries for complementary DNAs with retained introns represent them
      as artefacts that would not affect the proteome. Retroviruses are important model
      systems in studies of regulation of RNAs with retained introns, because their
      genomic and mRNAs contain one or more unspliced introns. For example, Mason
      Pfizer monkey virus overcomes cellular restrictions by using a cis-acting RNA
      element known as the constitutive transport element (CTE). The CTE interacts
      directly with the Tap protein (also known as nuclear RNA export factor 1, encoded
      by NXF1), which is thought to be a principal export receptor for cellular mRNA,
      leading to the hypothesis that cellular mRNAs with retained introns use cellular
      CTE equivalents to overcome restrictions to their expression. Here we show that
      the Tap gene contains a functional CTE in its alternatively spliced intron 10.
      Tap mRNA containing this intron is exported to the cytoplasm and is present in
      polyribosomes. A small Tap protein is encoded by this mRNA and can be detected in
      human and monkey cells. Our results indicate that Tap regulates expression of its
      own intron-containing RNA through a CTE-mediated mechanism. Thus, CTEs are likely
      to be important elements that facilitate efficient expression of mammalian mRNAs
      with retained introns.

PMID- 16971950
TI  - Palaeoanthropology: return of the last Neanderthal.

PMID- 16971951
TI  - Late survival of Neanderthals at the southernmost extreme of Europe.
AB  - The late survival of archaic hominin populations and their long contemporaneity
      with modern humans is now clear for southeast Asia. In Europe the extinction of
      the Neanderthals, firmly associated with Mousterian technology, has received much
      attention, and evidence of their survival after 35 kyr bp has recently been put
      in doubt. Here we present data, based on a high-resolution record of human
      occupation from Gorham's Cave, Gibraltar, that establish the survival of a
      population of Neanderthals to 28 kyr bp. These Neanderthals survived in the
      southernmost point of Europe, within a particular physiographic context, and are
      the last currently recorded anywhere. Our results show that the Neanderthals
      survived in isolated refuges well after the arrival of modern humans in Europe.

PMID- 16971952
TI  - Stoichiometry and turnover in single, functioning membrane protein complexes.
AB  - Many essential cellular processes are carried out by complex biological machines
      located in the cell membrane. The bacterial flagellar motor is a large membrane
      spanning protein complex that functions as an ion-driven rotary motor to propel
      cells through liquid media. Within the motor, MotB is a component of the stator
      that couples ion flow to torque generation and anchors the stator to the cell
      wall. Here we have investigated the protein stoichiometry, dynamics and turnover
      of MotB with single-molecule precision in functioning bacterial flagellar motors
      in Escherichia coli. We monitored motor function by rotation of a tethered cell
      body, and simultaneously measured the number and dynamics of MotB molecules
      labelled with green fluorescent protein (GFP-MotB) in the motor by total internal
      reflection fluorescence microscopy. Counting fluorophores by the stepwise
      photobleaching of single GFP molecules showed that each motor contains
      approximately 22 copies of GFP-MotB, consistent with approximately 11 stators
      each containing two MotB molecules. We also observed a membrane pool of
      approximately 200 GFP-MotB molecules diffusing at approximately 0.008 microm2 s(
      1). Fluorescence recovery after photobleaching and fluorescence loss in
      photobleaching showed turnover of GFP-MotB between the membrane pool and motor
      with a rate constant of the order of 0.04 s(-1): the dwell time of a given stator
      in the motor is only approximately 0.5 min. This is the first direct measurement
      of the number and rapid turnover of protein subunits within a functioning
      molecular machine.

PMID- 16971953
TI  - TGFB1 gene polymorphisms: their relevance in the susceptibility to Helicobacter
      pylori-related diseases.
AB  - Recent studies have revealed elevated expression of transforming growth factor
      beta1 (TGF-beta1) in gastric mucosa of patients with gastric cancer (GC) and
      those undergoing ulcer repair. As production of TGF-beta1 is genetically
      regulated, we aimed to assess whether functional polymorphisms of the TGFB1 gene
      are involved in susceptibility to and clinical characteristics of Helicobacter
      pylori-related diseases. DNA from 142 unrelated Spanish patients with GC, 200
      with peptic ulcer and 342 healthy controls was typed for the MspA1I T+869C, and
      the Sau96I G+915C polymorphisms of the TGFB1 gene using polymerase chain reaction
      and RFLP analysis. H. pylori infection and CagA/VacA antibody status were
      determined by Western blot in patients and controls. H. pylori infection (odds
      ratio (OR): 11.44; 95% confidence interval (CI): 4.45-29.42; P<0.001) and non
      steroidal anti-inflammatory drugs (OR: 5.07; 95% CI: 2.53-10.16; P<0.001) were
      identified as independent risks factors for duodenal ulcer (DU), whereas the
      TGFB1+869(*)C/C genotype was associated with reduced risk of developing the
      disease (OR: 0.32; 95% CI=0.15-0.68; P=0.003). Our results show that the TGFB1
      T+869C gene polymorphism is involved in the susceptibility to DU and provide
      further evidence that host genetic factors play a key role in the pathogenesis of
      H. pylori-related diseases.

PMID- 16971954
TI  - Haplotype-specific gene expression profiles in a telomeric major
      histocompatibility complex gene cluster and susceptibility to autoimmune
      diseases.
AB  - The telomeric class III region of the major histocompatibility complex is gene
      dense, but apart from the three tumour necrosis factor (TNF) superfamily members
      (TNF, lymphotoxin alpha and lymphotoxin beta) little is known of the expression
      and function of the majority of the genes. Recent genetic studies in autoimmune
      diseases, particularly rheumatoid arthritis (RA), have suggested a human
      leukocyte antigen (HLA)-DR-independent disease effect in this region. To gain
      further insights into these associations, we used lipopolysaccharide-stimulated
      human macrophages to examine inducible mRNA expression and genotype-phenotype
      relationships for genes in this region. Following stimulation in addition to the
      expected induction of TNF mRNA, a 14-fold increase of ATP6V1G2 at 18 h (P<0.001)
      was seen, whereas B-associated transcript (BAT)2 (P<0.001) and leucocyte-specific
      transcript (LST)1 (P<0.001) were both downregulated. By genotyping single
      nucleotide polymorphisms spanning a 70 kb interval centred on the TNF locus, we
      constructed haplotypes and determined associated expression profiles for 10 genes
      in the cluster using quantitative real-time polymerase chain reaction.
      Overexpression of BAT1 mRNA was associated with carriers of a haplotype
      containing the LST1 marker transmitted to RA cases in a family study and also
      DRB1(*)15 associated with susceptibility to nephritis in systemic lupus
      erythematosus. The implications of our findings for the understanding of genetic
      associations with disease susceptibility in this region are discussed.

PMID- 16971955
TI  - Meta-analysis of genome-wide linkage studies of systemic lupus erythematosus.
AB  - A genetic contribution to the development of systemic lupus erythematosus (SLE)
      is well established. Several genome-wide linkage scans have identified a number
      of putative susceptibility loci for SLE, some of which have been replicated in
      independent samples. This study aimed to identify the regions showing the most
      consistent evidence for linkage by applying the genome scan meta-analysis (GSMA)
      method. The study identified two genome-wide suggestive regions on 6p21.1-q15 and
      20p11-q13.13 (P-value=0.0056 and P-value=0.0044, respectively) and a region with
      P-value<0.01 on 16p13-q12.2. The region on chromosome 6 contains the human
      leukocyte antigen cluster, and the chromosome 16 and 20 regions have been
      replicated in several cohorts. The potential importance of the identified genomic
      regions are also highlighted. These results, in conjunction with data emerging
      from dense single nucleotide polymorphism typing of specific regions or future
      genome-wide association studies will help guide efforts to identify the actual
      predisposing genetic variation contributing to this complex genetic disease.

PMID- 16971956
TI  - Gene polymorphisms in Toll-like receptors, interleukin-10, and interleukin-10
      receptor alpha and lymphoma risk.
AB  - Interactions between environment and immune system play an essential role in the
      aetiology of immunopathologies, including lymphomas. Toll-like receptors (TLR)
      belong to a group of pattern recognition receptors, with importance for innate
      immune response and inflammatory processes. Interleukin-10 (IL-10) is a key
      regulatory cytokine and has been implicated in lymphomagenesis. Functional
      polymorphisms in these inflammation-associated genes may affect the
      susceptibility towards lymphoma. To test this hypothesis, we have genotyped DNA
      of 710 lymphoma cases and 710 controls within the context of a population-based
      epidemiological study for 11 functionally important single-nucleotide
      polymorphisms in TLR1, -2, -4, -5, -9, IL10 and IL10 receptor (IL10RA). The
      IL10RA Ser138Gly variant was underrepresented among lymphoma cases (odds ratio
      (OR)=0.81, 95 per cent confidence interval (95% CI)=0.65-1.02), mainly owing to
      an inverse association with Hodgkin's lymphoma (HL). The TLR2 -16933T>A variant
      was associated with a 2.8-fold increased risk of follicular lymphoma (95% CI=1.43
      5.59) and a decreased risk of chronic lymphocytic leukaemia (OR=0.61, 95% CI=0.38
      0.95). Furthermore, the TLR4 Asp299Gly variant was positively associated with the
      risk of mucosa-associated lymphoid tissue lymphoma (OR=2.76, 95% CI=1.12-6.81)
      and HL (OR=1.80, 95% CI=0.99-3.26). In conclusion, this study suggests an effect
      of polymorphisms in factors of the innate immune response in the aetiology of
      some lymphoma subtypes.

PMID- 16971957
TI  - A distinct inflammatory gene expression profile in patients with psoriatic
      arthritis.
AB  - Psoriatic arthritis (PsA) is a systemic inflammatory condition featuring
      polyarthritis associated with psoriasis. Apart from clinical indicators, few
      biomarkers exist to aid in the diagnosis and management of PsA. We hypothesized
      that whole blood gene expression profiling would provide new diagnostic markers
      and/or insights into pathogenesis of the disease. We compared whole blood gene
      expression profiles in PsA patients and in age-matched controls. We identified
      310 differentially expressed genes, the majority of which are upregulated in PsA
      patients. The PsA expression profile does not significantly overlap with profiles
      derived from patients with rheumatoid arthritis or systemic lupus erythematosus.
      Logistic regression identified two lymphocyte-specific genes (zinc-finger protein
      395 and phosphoinositide-3-kinase 2B) that discriminate PsA patients from normal
      controls. In addition, a highly coregulated cluster of overexpressed genes
      implicated in protein kinase A regulation strongly correlates with erythrocyte
      sedimentation rate. Other clusters of coregulated, yet suppressed genes in PsA
      patient blood include molecules involved in T-cell signaling. Finally,
      differentially expressed genes in PsA fall into diverse functional categories,
      but many downregulated genes belong to a CD40 signaling pathway. Together, the
      data suggest that gene expression profiles of PsA patient blood contain candidate
      novel disease markers and clues to pathogenesis.

PMID- 16971958
TI  - Education as an important risk factor for the prevalence of hypertension and
      elevated blood pressure in Chinese men and women.

PMID- 16971959
TI  - The effect of genetic variation in angiotensinogen on serum levels and blood
      pressure: a comparison of Nigerians and US blacks.
AB  - Molecular variants of angiotensinogen (AGT) have been associated with AGT level
      and hypertension (HT). However, results from reported studies vary considerably
      between- and within-studied populations. We performed association analysis of AGT
      gene variants with AGT levels and HT in samples of African descent families,
      including 595 Nigerians and 901 African Americans. We evaluated association using
      haplotypes defined by a set of single-nucleotide polymorphisms selected from a
      previous detailed study of the gene haplotype structure. In the sample of
      Nigerian families, AGT haplotype H1 was associated with high plasma level.
      Results were not significant for blood pressure (BP) or HT. For the African
      American population, we found significant association between low plasma AGT
      level and haplotype H7. Furthermore, we found weak associations of H1 with
      hypertensive status and H7 with low systolic BP. However, no significant
      association between H1 and high plasma level was found. We conclude that the two
      distantly related haplotypes, H1 and H7, are associated, but have opposite
      effects on the phenotypes in two populations of African origin.

PMID- 16971961
TI  - Peaking of MMP-26 and TIMP-4 marks invasive transition in prostate cancer.

PMID- 16971967
TI  - RNA interference for the treatment of cancer.
AB  - RNA interference (RNAi) is the latest new technology in the field of genetic
      medicine in which specific genes can be turned off, or silenced, so as to affect
      a therapeutic outcome. It can be highly specific, works in the nanomolar range
      and is far more effective than the antisense approaches popular 10-15 years ago.
      Here we review the field and explore the potential role of RNAi in cancer
      therapy, highlighting recent progress and examining the hurdles that must be
      overcome before this promising technology is ready for clinical use.

PMID- 16971968
TI  - CDK/GSK-3 inhibitors as a new approach for the treatment of proliferative renal
      diseases.
AB  - Proliferation of specific renal cell types leads to the development of many types
      of kidney disease. Given the central role that both cyclin-dependent kinases
      (CDKs) and glycogen synthase kinase-3 (GSK-3) play in promoting aberrant
      proliferation within the kidney, these paralogous serine/threonine kinases are
      being explored as therapeutic molecular targets in proliferative renal diseases.
      CDK/GSK-3 inhibitors have now demonstrated efficacy in preclinical models of
      mesangial proliferative glomerulonephritis, crescentic glomerulonephritis,
      proliferative lupus nephritis and collapsing glomerulopathy. Moreover, they have
      recently entered human clinical trials in IgA nephropathy. Since the pathogenesis
      of most proliferative renal diseases is multifactorial, there is the belief that
      CDK/GSK-3 inhibitors, as inherently promiscuous drugs, may have several modes of
      action. This is supported by recent studies in systems research delineating the
      antiinflammatory profile of CDK/GSK-3 inhibitors compared with other
      immunomodulators. Thus, CDK/GSK-3 inhibitors may emerge as effective drugs for
      proliferative renal diseases due to their integrative properties across several
      aspects of disease pathogenesis. This brief mini-review will highlight these
      issues.

PMID- 16971966
TI  - Molecular Basis of Steroid Action in the Prostate.

PMID- 16971965
TI  - Resource Letter: LBOT-1: Laser-based optical tweezers.
AB  - This Resource Letter provides a guide to the literature on optical tweezers, also
      known as laser-based, gradient-force optical traps. Journal articles and books
      are cited for the following main topics: general papers on optical tweezers,
      trapping instrument design, optical detection methods, optical trapping theory,
      mechanical measurements, single molecule studies, and sections on biological
      motors, cellular measurements and additional applications of optical tweezers.

PMID- 16971969
TI  - Adenoviral gene therapy in head and neck cancer.
AB  - Despite advances in surgical techniques, improvement in radiation therapy and the
      addition of new biological agents such as cetuximab to traditional chemotherapy,
      the median survival of patients with head and neck cancer has changed little over
      the past few decades. However, recent advances in the fundamental understanding
      of head and neck cancer biology suggest that targeting molecular pathways
      underlying carcinogenesis may provide alternative or additional approaches to the
      treatment of head and neck cancer. Viruses, particularly adenoviruses, have been
      critical in the application and development of these molecular approaches.
      Adenoviruses have been engineered to function as vectors for delivering
      therapeutic genes for gene therapy. The purpose of this review is to provide a
      prospective on the use of adenoviruses in head and neck cancer therapy by
      examining clinical trials of adenovirus-mediated p53 gene therapy and by
      reviewing the application of a promising oncolytic adenovirus, ONYX-015, in head
      and neck cancer.

PMID- 16971970
TI  - Spotlight on targeting aminoacyl-tRNA synthetases for the treatment of fungal
      infections.
AB  - This month's Spotlight on... focuses on targeting aminoacyl-tRNA synthetases for
      the treatment of fungal infections. The emergence of drug-resistant strains of
      bacterial and fungal pathogens has led to the development of new antibiotic
      strategies. Aminoacyl-tRNA synthetases, crucial for protein synthesis, represent
      a new target for the treatment of different infectious diseases.

PMID- 16971971
TI  - Molecule of the month. Vorinostat.

PMID- 16971972
TI  - Emerging therapeutic strategies for chronic inflammatory diseases.
AB  - The 6th edition of the "Days of Molecular Medicine" conference was held at the
      Karolinska Institute in Stockholm, Sweden, May 24-27, 2006, and focused on the
      role of inflammation in chronic disease. The meeting, organized by The Nature
      Publishing Group, the Massachusetts General Hospital and the Karolinska
      Institute, brought together an international panel of speakers who discussed
      recent advances in the molecular pathology of chronic inflammatory diseases. This
      congress report summarizes the most relevant presentations highlighting novel
      targets for therapeutic intervention.

PMID- 16971973
TI  - Advances and perspectives in the field of gene transfer technology.
AB  - The American Society of Gene Therapy 9th annual meeting, held May 31 to June 4,
      2006, in Baltimore (Maryland, U.S.A.), focused on several aspects of gene
      transfer technology, such as vector development of a wide variety of gene
      delivery systems, stem cell research, gene expression, engineering of cell and
      animal models for the study of several pathological conditions, genetic
      immunization procedures, immunogenicity of vectors and transgenes, insertional
      mutagenesis and last, but not least, clinical and preclinical studies. Some
      advances were reported in the field of gene transfer technology; however, safety
      issues, such as insertional mutagenesis, and improvement of vector design remain
      at the top of the agenda of gene therapists.

PMID- 16971974
TI  - Cardiovascular diseases and diabetes mellitus.
AB  - Diabetes UK held its Annual Professional Conference on March 29-31, 2006, in
      Birmingham, United Kingdom. This conference aimed to deliver the latest global
      developments in diabetes care using basic and clinical science as its
      cornerstone, and to inspire and support innovation in current practice. This
      report will examine the advances in different aspects of cardiovascular disease
      in diabetes mellitus.

PMID- 16971975
TI  - Universal access: but when? Treating the right patient at the right time: access
      to cardiac rehabilitation.
AB  - The Canadian Cardiovascular Society formed an Access to Care Working Group
      ('Working Group') in the spring of 2004. The mandate of the group was to use the
      best science and information to establish reasonable triage categories and safe
      wait times for access to common cardiovascular services and procedures. The
      present commentary presents the rationale for benchmarks for cardiac
      rehabilitation (CR) services. The Working Group's search for evidence included: a
      full literature review of the efficacy of CR, and the factors affecting access
      and referral to CR; a review of existing guidelines for access to CR; and a
      national survey of 14 CR programs across Canada undertaken in May 2005 to solicit
      information on referral to, and wait times for, CR. The Working Group also
      reviewed the results of The Ontario Cardiac Rehabilitation Pilot Project (2002)
      undertaken by the Cardiac Care Network of Ontario, which reported the average and
      median wait times for CR. Some international agencies have formulated their own
      guidelines relating to the optimal wait time for the onset of CR. However, due to
      the limited amount of supporting literature, these guidelines have generally been
      formed as consensus statements. The Canadian national survey showed that few
      programs had guidelines for individual programs. The Cardiac Care Network of
      Ontario pilot project reported that the average and median times from a cardiac
      event to the intake into CR were 99 and 70 days, respectively. The national
      survey of sampled CR programs also revealed quite remarkable differences across
      programs in terms of the length of time between first contact to first attendance
      and to commencement of exercise. Programs that required a stress test before
      program initiation had the longest wait for exercise initiation. Some patients
      need to be seen within a very short time frame to prevent a marked deterioration
      in their medical or psychological state. In some cases, early intervention and
      advocacy may reduce the risk of loss of employment. Or, there may be profound
      disturbances in the patient's family as a result of the cardiac event. For other
      patient groups, preferable wait times vary from one to 30 days, and acceptable
      wait times vary from seven to 60 days. All cardiovascular disease patients
      require core aspects of CR services. Patients who would derive benefit from
      formal CR programs should be provided the opportunity, given the proven efficacy
      and cost effectiveness of CR.

PMID- 16971977
TI  - Endothelial progenitor cell-seeded grafts: rash and risky.
AB  - The patency of prosthetic vascular grafts is impaired by intimal hyperplasia (IH)
      near the anastomotic regions. The absence of a functional endothelial monolayer
      on the prosthetic grafts is an important stimulus for IH. To improve the outcome
      of synthetic vascular bypass surgery, cell seeding is a promising concept that
      has been extensively investigated and is still evolving. In the present paper,
      the concept of prosthetic graft cell seeding is discussed, with emphasis on its
      newest era: seeding with endothelial progenitor cells. Although experimental
      studies on prosthetic graft seeding using endothelial progenitor cells have shown
      excellent results on graft endothelialization, none of these studies reported
      favourable effects on the more clinically relevant end points such as IH or graft
      patency.

PMID- 16971976
TI  - Canadian Cardiovascular Society position statement--recommendations for the
      diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease.
AB  - Since the last publication of the recommendations for the management and
      treatment of dyslipidemia, new clinical trial data have emerged that support a
      more vigorous approach to lipid lowering in specific patient groups. The decision
      was made to update the lipid guidelines in collaboration with the Canadian
      Cardiovascular Society. A systematic electronic search of medical literature for
      original research consisting of blinded, randomized controlled trials was
      performed. Meta-analyses of studies of the efficacy and safety of lipid-lowering
      therapies, and of the predictive value of established and emerging risk factors
      were also reviewed. All recommendations are evidence-based, and have been
      reviewed in detail by primary and secondary review panels. Major changes include
      a lower low-density lipoprotein cholesterol (LDL-C) treatment target (lower than
      2.0 mmol/L) for high-risk patients, a slightly higher intervention point for the
      initiation of drug therapy in most low-risk individuals (LDL-C of 5.0 mmol/L or a
      total cholesterol to high-density lipoprotein cholesterol ratio of 6.0) and
      recommendations regarding additional investigations of potential use in the
      further evaluation of coronary artery disease risk in subjects in the moderate
      risk category.

PMID- 16971978
TI  - Are complex coronary lesions more frequent in patients with diabetes mellitus?
AB  - BACKGROUND: Coronary atherosclerotic burden is excessive in diabetic patients.
      Diabetes mellitus (DM) is an independent predictor for both death and myocardial
      infarction. It is not known whether the prevalence of complex coronary lesions,
      such as bifurcation and ostial lesions, is different in diabetics from
      nondiabetics. OBJECTIVE: The aim of present study was to investigate the
      prevalence of these lesions in patients with DM. METHODS: One thousand fourteen
      consecutive patients (mean age 61.3+/-10.7 years) were investigated. Coronary
      angiograms were examined for bifurcation and ostial lesions using a digital
      quantitative system. Patients were classified as diabetic (n=281) or nondiabetic
      (n=733). RESULTS: Patient mean age, and rates of hypertension and hyperlipidemia
      were significantly higher in the diabetic group than in the nondiabetic group
      (P<0.0001), although smoking was significantly lower (P=0.001). Reasons for
      coronary angiography and treatment were comparable between the two groups. The
      prevalence of bifurcation lesions and ostial lesions was significantly greater in
      the diabetic group than in the nondiabetic group (9.8% versus 4.3% [P=0.001] and
      38.4% versus 29.2% [P=0.003] in the diabetic group versus the nondiabetic group).
      The presence of DM and greater age were found to be independent predictors for
      bifurcation lesions (OR=2.27 [P=0.004] and OR=1.03 [P=0.01], for DM and age,
      respectively) and ostial lesions (OR=1.40 [P=0.027] and OR=1.02 [P=0.001], for DM
      and age, respectively) in multivariate analysis. CONCLUSIONS: Complex coronary
      lesions such as bifurcation and ostial lesions were significantly more common in
      diabetic patients than in nondiabetic patients. Greater age and the presence of
      DM were independent predictors for these complex lesions. These results may help
      to explain the poor prognosis of coronary artery disease among diabetic patients.

PMID- 16971979
TI  - The clinical effect and tolerability of ezetimibe in high-risk patients managed
      in a specialty cardiovascular risk reduction clinic.
AB  - INTRODUCTION: Ezetimibe (EZ) is a selective cholesterol absorption inhibitor
      approved for use in Canada. The effect and tolerability of EZ among patients was
      evaluated in the clinical setting of a specialty cardiovascular risk reduction
      clinic at the University of Alberta Hospital, Edmonton, Alberta. patients and
      METHODS: All patients 18 years of age or older who were prescribed EZ were
      included, unless they failed to take EZ for a minimum of two weeks, did not have
      baseline and on-EZ low-density lipoprotein cholesterol (LDL-C) levels, or had
      concomitant lipid-lowering drugs or dosages changed within one month of starting
      EZ. RESULTS: Eighty-four patients (mean age 57.9 years) were included. By
      Framingham risk calculation, 71.4% were found to be high-risk patients, 13.1%
      moderate-risk patients and 15.5% low-risk patients; 66.7% of patients had prior
      cardiovascular events. On EZ, the mean reductions were: total cholesterol level
      1.11 mmol/L (16.5%); LDL-C level 1.01 mmol/L (22.3%); high-density lipoprotein
      cholesterol level 0.06 mmol/L (4.6%); and ratio of total cholesterol level to
      high-density lipoprotein cholesterol level 0.68 mmol/L (12.8%); all were
      statistically significant (P<0.001). Results were similar when stratified by
      primary (n=28) versus secondary (n=56) prevention. Patients on EZ monotherapy
      (n=34) had mean LDL-C reductions of 1.03 mmol/L (20.5%) compared with 1.19 mmol/L
      (30.1%) or 0.95 mmol/L (22.5%), where EZ was added to low-dose or high-dose
      statins (P<0.01 for all). On EZ, 30 patients (35.7%) achieved previously
      unattainable target LDL-C levels. Four patients discontinued the drug due to side
      effects. CONCLUSIONS: EZ is safe and effective in high-risk patients treated in
      the clinical setting of a cardiovascular risk reduction clinic. A mean LDL-C
      reduction of 1 mmol/L (20% to 30%) in all patient subgroups is consistent with
      previous clinical trial results. The significant reduction in LDL-C (mean 22.5%)
      observed in the EZ plus high-dose statin subgroup provides clinical evidence for
      use of this medication beyond published studies.

PMID- 16971980
TI  - Reactive oxygen species and vascular remodelling in hypertension: still alive.
AB  - Reactive oxygen species (ROS) are reactive derivatives of O2 metabolism,
      including superoxide anion, hydrogen peroxide, hydroxyl radical and nitric oxide.
      All types of vascular cells produce ROS, primarily via cell membrane-associated
      NAD(P)H oxidase. Cardiovascular diseases, such as hypertension, are associated
      with increased ROS formation (oxidative stress). Oxidative excess in the
      vasculature reduces levels of the vasodilator nitric oxide, causes tissue injury,
      promotes protein oxidation and DNA damage, and induces proinflammatory responses.
      ROS are also important intracellular signalling molecules that regulate vascular
      function by modulating vascular cell contraction/dilation, migration,
      growth/apoptosis, and extracellular matrix protein turnover, which contribute to
      vascular remodelling. Interventions to decrease ROS bioavailability regress
      remodelling and reduce blood pressure in experimental hypertension. Such
      strategies may have therapeutic potential in cardiovascular diseases.

PMID- 16971983
TI  - Large molecular aggregates: From atmospheric aerosols to drug nanoparticles.
AB  - Large molecular aggregates with sizes ranging from subnanometers to microns are
      ubiquitous. As atmospheric aerosols they influence our climate, in interstellar
      space they are discussed as reactive sites, and in medicine small particles are
      considered as promising candidates to achieve a targeted drug delivery. The
      present contribution is focused on the characterization of the physical-chemical
      properties of these particles and on their targeted generation. One of the
      greatest challenges is to understand the properties of these aggregates on a
      molecular level. The latter point is discussed in detail focussing on the
      vibrational dynamics of these particles.

PMID- 16971982
TI  - Brucella endocarditis in prosthetic valves.
AB  - Human brucellosis is a multiple organ disease that presents with fever and is
      most often transmitted via contaminated, unpasteurized goat milk and cheese. In
      chronic cases, focal complications (eg, spondylitis, neurobrucellosis and
      endocarditis) are frequently seen. Although the disease may be severely
      debilitating, the mortality rate is low. Fatal cases are often due to
      endocarditis. Because Brucella endocarditis is a rare complication (2% to 5%),
      therapeutic considerations are based on single-case experiences only. Therapy
      includes long-term antibiotic treatment using combinations of various
      antimicrobial drugs and surgical valve replacement when required. A case of
      Brucella endocarditis complicated by the infection of two valvular prostheses
      implanted after involvement of the mitral and aortic valve due to rheumatic fever
      is described. The patient was successfully treated by a medical and surgical
      approach. Therapeutic strategies in Brucella endocarditis are discussed in light
      of the current literature.

PMID- 16971984
TI  - Molecular dynamics simulations of the aqueous interface with the [BMI][PF6] ionic
      liquid: Comparison of different solvent models.
AB  - We report a Molecular Dynamics (MD) study of the interface between water and the
      hygroscopic room temperature Ionic Liquid "IL" [BMI][PF6] (1-butyl-3-methyl
      imidazolium hexafluorophosphate), comparing the TIP3P, SPC/E and TIP5P models for
      water and two IL models where the ions are +/-1 or +/-0.9 charged. A recent MD
      study (A. Chaumont, R. Schurhammer and G. Wipff, J. Phys. Chem. B, 2005, 109,
      18964) showed that using TIP3P water in conjunction with the IL(+/-1) model led
      to water-IL mixing without forming an interface, whereas a biphasic system could
      be obtained with the IL(+/-0.9) model. With the TIP5P and SPC/E models, the
      juxtaposed aqueous and IL phases are found to remain distinct for at least 20 ns.
      The resulting IL humidity, exaggerated with the IL(+/-1) model, is in better
      agreement with experiment using the IL(+/-0.9) model. We also report demixing
      simulations on the "randomly mixed" liquids, using the IL(+/-0.9) model for the
      ionic liquid. With the three tested water models, the phases separate very slowly
      ( approximately 20 ns or more) compared to "classical" chloroform-water mixtures
      (less than 1 ns), leading to biphasic systems similar to those obtained after
      equilibration of the juxtaposed liquids. The characteristics of the interface
      (size, polarity, ion orientation, electrostatic potential) are compared with the
      different models. Possible reasons why, among the three tested water models, the
      widely-used TIP3P model exaggerates the inter-solvent mixing, are analyzed. The
      difficulty in computationally and experimentally equilibrating water-IL mixtures
      is attributed to the slow dynamics and micro-heterogeneity of the IL and to the
      different states of water in the IL phase.

PMID- 16971985
TI  - New organic noble gas molecules: energetics, stability and potential energy
      surfaces of HCCXeCCH and HCCKrCCH.
AB  - The diacetylides of Xe and Kr, HCCXeCCH and HCCKrCCH, are predicted to exist as
      metastable, chemically-bound compounds. The electronic structure, properties of
      the potential energy surfaces and decomposition paths are computed and analyzed.
      MP2, MCSCF and CASPT2 ab initio methods are used, as appropriate for each of the
      properties studied. Using transition state theory and the computed barrier for
      decomposition, the lifetime of HCCXeCCH is calculated as a function of
      temperature. The molecule is predicted to be stable well above the cryogenic
      range, with a lifetime of 24 h at 200 K. The implications for organic chemistry
      of the noble gases are discussed.

PMID- 16971986
TI  - Diffusion in binary gas mixtures studied by NMR of hyperpolarized gases and
      molecular dynamics simulations.
AB  - The dependence of the individual mean square displacement of rare gases in binary
      mixtures is studied by a combined experimental and theoretical approach. We show
      that the diffusion constant can be varied in a considerable range by changing the
      molar fractions of the mixtures. On the experimental side, NMR diffusion
      measurements are done on hyperpolarized 3He and 129Xe, mixed with several inert
      buffer gases, in the presence of a magnetic field gradient. The results are
      compared to diffusion coefficients obtained from atomistic molecular dynamics
      simulations based on Lennard-Jones type potentials of the corresponding gas
      mixtures, and to appropriate analytical expressions, yielding very good mutual
      agreement. This study is the first quantitative validation of the effects of the
      mutual interactions between gas particles on the individual diffusion properties.
      It is shown that the dependency of gas phase diffusion properties on the local
      chemical environment may not be neglected, e.g. in diffusion-controlled chemical
      reactions.

PMID- 16971981
TI  - Myofibrillar remodeling in cardiac hypertrophy, heart failure and
      cardiomyopathies.
AB  - BACKGROUND: A wide variety of pathological conditions have been shown to result
      in cardiac remodelling and myocardial dysfunction. However, the mechanisms of
      transition from adaptive to maladaptive alterations, as well as those for changes
      in cardiac performance leading to heart failure, are poorly understood.
      OBSERVATIONS: Extensive studies have revealed a broad spectrum of progressive
      changes in subcellular structures and function, as well as in signal transduction
      and metabolism in the heart, among different cardiovascular disorders. The
      present review is focused on identifying the alterations in molecular and
      biochemical structure of myofibrils (myofibrillar remodelling) in hypertrophied
      and failing myocardium in different types of heart diseases. Numerous changes at
      the level of gene expression for both contractile and regulatory proteins have
      already been reported in failing hearts and heart diseases; these changes are
      potential precursors for heart failure such as cardiac hypertrophy and
      cardiomyopathies. Myofibrillar remodelling, as a consequence of proteolysis,
      oxidation, and phosphorylation of some functional groups in both contractile and
      regulatory proteins in hearts failing due to different etiologies, has also been
      described. CONCLUSIONS: Although myofibrillar remodelling appears to be
      associated with cardiac dysfunction, alterations in both contractile and
      regulatory proteins are dependent on the type and stage of heart disease.

PMID- 16971987
TI  - Quantum chemical modelling of the rate determining step for oxygen reduction on
      quinones.
AB  - Two inner-sphere electrocatalytic channels for quinone-mediated reduction of
      molecular oxygen to form hydrogen peroxide have been addressed by means of
      density functional theory. Each of the channels comprises an initial rate
      determining chemical step and a subsequent electrochemical reduction step by
      which peroxide is produced. The reduction mechanism was determined for 9,10
      anthraquinone and 9,10-phenanthrenequinone and the quantum chemical results are
      compared with experimental results. Two distinctly different structures were
      determined for the critical chemical step depending on whether the catalytic site
      is present as HQ* or Q*-. While a superoxo species is formed on HQ*, a van der
      Waals (vdW) type compound is formed on Q*-. It is shown that the Gibbs energy of
      activation for the semiquinone/oxygen reaction is largely determined by the
      entropy term. The results explain the experimentally observed pH dependence of
      the O2 reduction rate on quinone functionalised electrodes.

PMID- 16971988
TI  - On the nature of liquid junction and membrane potentials.
AB  - Whenever a spatially inhomogeneous electrolyte, composed of ions with different
      mobilities, is allowed to diffuse, charge separation and an electric potential
      difference is created. Such potential differences across very thin membranes
      (e.g. biomembranes) are often interpreted using the steady state Goldman
      equation, which is usually derived by assuming a spatially constant electric
      field. Through the fundamental Poisson equation of electrostatics, this implies
      the absence of free charge density that must provide the source of any such
      field. A similarly paradoxical situation is encountered for thick membranes (e.g.
      in ion-selective electrodes) for which the diffusion potential is normally
      interpreted using the Henderson equation. Standard derivations of the Henderson
      equation appeal to local electroneutrality, which is also incompatible with
      sources of electric fields, as these require separated charges. We analyse self
      consistent solutions of the Nernst-Planck-Poisson equations for a 1 : 1-univalent
      electrolyte to show that the Goldman and Henderson steady-state membrane
      potentials are artefacts of extraneous charges created in the reservoirs of
      electrolyte solution on either side of the membrane, due to the unphysical nature
      of the usual (Dirichlet) boundary conditions assumed to apply at the membrane
      electrolyte interfaces. We also show, with the aid of numerical simulations, that
      a transient electric potential difference develops in any confined, but initially
      non-uniform, electrolyte solution. This potential difference ultimately decays to
      zero in the real steady state of the electrolyte, which corresponds to
      thermodynamic equilibrium. We explain the surprising fact that such transient
      potential differences are well described by the Henderson equation by using a
      computer algebra system to extend previous steady-state singular perturbation
      theories to the time-dependent case. Our work therefore accounts for the success
      of the Henderson equation in analysing experimental liquid-junction potentials.

PMID- 16971989
TI  - Electropolishing of stainless steels in a choline chloride based ionic liquid: an
      electrochemical study with surface characterisation using SEM and atomic force
      microscopy.
AB  - We have studied the anodic dissolution (electropolishing) of various stainless
      steel alloys in an ionic liquid comprising a 2 : 1 stoichiometric mix of ethylene
      glycol (EG) and choline chloride. We have used a combination of electrochemical
      and spectroscopic methods together with in situ liquid probe microscopy. We
      discuss the role and influence of the surface oxide passivation layer,
      characterized here by X-ray photoelectron spectroscopy (XPS) and linear sweep
      voltammetry, on the polishing process. We address the question of dealloying
      during the polish in order to contribute to our understanding of the viability of
      the ionic liquid as a replacement industrial electropolishing medium; the current
      commercial process uses a corrosive mixture of phosphoric and sulfuric acids.
      Also, we present data from ex situ and in situ liquid AFM studies giving both a
      qualitative and quantitative insight into the nature and scale of morphological
      changes at the steel surface during the polishing process.

PMID- 16971991
TI  - Bright luminescence from silane substituted and bridged silicon nanoclusters.
AB  - Time-dependent density functional theory (TDDFT) calculations show that silicon
      nanoclusters (Si-NC) capped by linear silane groups have large oscillator
      strengths of the same magnitude as reported in recent experimental studies. We
      propose a mechanism where linear silanes attached to the Si-NC surface affect the
      optical properties enhancing the oscillator strengths and thereby accounting for
      the bright luminescence observed in the blue region of the visible spectrum. The
      anisotropic emission seen experimentally can also be explained by the presence of
      the silane groups on the cluster surface. The excitation energies are found to be
      only slightly affected by the silanes, whereas the oscillator strengths increase
      with the length of the silane chain and are significantly larger than obtained
      for unsubstituted Si-NCs. In TDDFT studies of Si-NC dimers interconnected by a
      linear silane bridge, we obtained large oscillator strengths indicating that such
      structures could be useful light sources for optical devices.

PMID- 16971990
TI  - Switching electrical conductivity in an AOT-isooctane-water microemulsion through
      photodimerization of solubilized N-methyl-2-quinolone.
AB  - The electrical conductivity of microemulsions composed of Aerosol OT (AOT),
      isooctane and water as a function of temperature was studied in the absence and
      presence of N-methyl-2-quinolone (NMQ), and consequences of an in situ
      photodimerization of NMQ were investigated. A conductivity increase upon raising
      the temperature of a water-in-oil microemulsion indicates percolation.
      Percolation temperatures (Tp) can be influenced specifically by the addition of
      certain substances. Small amounts of solubilized N-methyl-2-quinolone induce
      lower Tp (by up to 9 K), and photodimerization of NMQ shifts Tp back to higher
      values. Consequently, the microemulsion can be switched from conducting to non
      conducting without varying temperature or composition by exposing samples to UV
      light at lambda > 310 nm. The effect can be reverted in part by irradiation at
      lambda = 250 nm. Coumarin derivatives--structurally related to NMQ--show much
      slighter effects.

PMID- 16971992
TI  - Polyelectrolytes in solutions with multivalent salt. Effects of flexibility and
      contour length.
AB  - It has been experimentally observed that trivalent ions are capable of promoting
      compaction of semi-flexible polyelectrolyte chains. In this work we perform Monte
      Carlo simulations on single chain model systems with varying chain size and
      stiffness and evaluate the action of multivalent salt on the chain conformation.
      It is observed that longer chains tend to achieve relatively more compact
      conformations than shorter ones, and the dimensions of the collapsed structures
      do not significantly vary with contour length. The influence of contour length
      and intrinsic stiffness in the process of ion condensation is studied by analysis
      of the ion-ion nearest-neighbor distribution. The general trend is an increase of
      the degree of ion condensation as the chain length increases, in accordance with
      experimental evidence. A decreased importance of end-effects and, especially,
      larger volume charge densities are responsible for such behavior. The influence
      of chain stiffness is nontrivial, and depends on salt concentration. The results
      emphasize the complex nature of ion-correlation phenomena in flexible or semi
      flexible chains and call for the development of more sophisticated analytical
      theories.

PMID- 16971993
TI  - Comparison of complex coacervate core micelles from two diblock copolymers or a
      single diblock copolymer with a polyelectrolyte.
AB  - With light scattering titrations, we show that complex coacervate core micelles
      (C3Ms) form from a diblock copolymer with a polyelectrolyte block and either an
      oppositely charged polyelectrolyte, a diblock copolymer with an oppositely
      charged polyelectrolyte or a mixture of the two. The effect of added salt and pH
      on both types of C3Ms is investigated. The hydrodynamic radius of mixed C3Ms can
      be controlled by varying the percentage of oppositely charged polyelectrolyte or
      diblock copolymer. A simple core-shell model is used to interpret the results
      from light scattering, giving the same trends as the experiments for both the
      hydrodynamic radii and the relative scattering intensities. Temperature has only
      a small effect on the C3Ms. Isothermal titration calorimetry shows that the
      complexation is mainly driven by Coulombic attraction and by the entropy gain due
      to counterion release.

PMID- 16971994
TI  - Digital radiography.
AB  - Digital radiography has been used in human medical imaging since the 1980s with
      recent and rapid acceptance into the veterinary profession. Using advanced image
      capture and computer technology, radiographic images are viewed on a computer
      monitor. This is advantageous because radiographic images can be adjusted using
      dedicated computer software to maximize diagnostic image quality. Digital images
      can be accessed at computer workstations throughout the hospital, instantly
      retrieved from computer archives, and transmitted via the internet for
      consultation or case referral. Digital radiographic data can also be incorporated
      into a hospital information system, making record keeping an entirely paperless
      process. Digital image acquisition is faster when compared to conventional screen
      film radiography, improving workflow and patient throughput. Digital radiography
      greatly reduces the need for 'retake' radiographs because of wide latitude in
      exposure factors. Also eliminated are costs associated with radiographic film and
      x-ray film development. Computed radiography, charged coupled devices, and flat
      panel detectors are types of digital radiography systems currently available.

PMID- 16971995
TI  - Osteoinductive properties of the bone marrow--myth or reality.
AB  - The osteogenic potential of red bone marrow was first reported more than 100
      years ago. Since then, studies have reported controversial results that do not
      confirm nor disprove the capacity of fresh red bone marrow to produce bone.
      Researches have been focused on techniques that improve the efficiency of the
      bone marrow, including: the increase of the concentration of the mesenchymal stem
      cells in the aspirated bone marrow, the combination with a 'carrier' that helps
      to maintain the mesenchymal stem cells and guides and supports the vascular
      ingrowth in the defect, or the combination with bone growth factors that
      stimulate the marrow stromal cells to differentiate into bone forming cells. Each
      of these techniques has its drawbacks and increases the expenses of an operation.
      On the other hand, the synergistic effect observed with these combinations does
      not resolve the problem of the osteogenic capacity of pure bone marrow, which
      still remains questionable.

PMID- 16971996
TI  - A comparative study of articular cartilage thickness in the stifle of animal
      species used in human pre-clinical studies compared to articular cartilage
      thickness in the human knee.
AB  - Histological measurements of the thickness of non-calcified and calcified
      cartilage, as well as the subchondral bone plate in five locations on the femoral
      trochlea and medial femoral condyles of species were used in preclinical studies
      of articular cartilage and compared to those of the human knee. Cadaver specimens
      were obtained of six human knees, as well as six equine, six goat, six dog, six
      sheep and six rabbit stifle joints (the animal equivalent of the human knee).
      Specimens were taken from the lateral trochlear ridge, medial trochlear ridge and
      medial femoral condyle. After histopathological processing, the thickness of non
      calcified and calcified cartilage layers, as well as the subchondral bone plate,
      was measured. Average articular cartilage thickness over five locations were 2.2
      2.5 mm for human, 0.3 mm for rabbit, 0.4-0.5 mm for sheep, 0.6-1.3 mm for dog,
      0.7-1.5 mm for goat and 1.5-2 mm for horse. The horse provides the closest
      approximation to humans in terms of articular cartilage thickness, and this
      approximation is considered relevant in pre-clinical studies of cartilage
      healing.

PMID- 16971997
TI  - Mosaicplasty with photooxidized, mushroom shaped, bovine, osteochondral
      xenografts in experimental sheep.
AB  - The goal was to study the performance of mushroom shaped, photooxidized,
      osteochondral grafts in mosaicplasty focusing on graft stability and survival.
      Mushroom shaped, photooxidized grafts (6 mm for the cartilaginous head of the
      mushroom, 3 mm for the stem) were implanted in the medial femoral condyle of 10
      sheep. Four transplants were inserted per condyle in an overlapping fashion using
      the pressfit technique (n=40 grafts in 10 condyles). The grafts were followed for
      6 and 12 months. Semi-quantitative evaluation of graft performance was performed
      using a validated score system. All grafts were mechanically stable at 6 and 12
      months with one exception, where the mushroom head broke off. The formation of
      cystic lesions in the subchondral bone area was minimal. Repopulation of the old
      photooxidized cartilage was noticed with cells invading the matrix from the
      subchondral bone area and also from the pannus on the surface. Fusion between
      host and graft cartilage was observed in some of the grafts at 12 months, while
      remodeling of the calcified cartilage zone and tidemark was noticed in all
      grafts. Results scored significantly better for the 6 months compared to the 12
      months group if cartilage surface integrity was compared (p<0.05). In all other
      variables no significant differences were found between groups. Despite moderate
      graft recession in the 12 months group partial fusion of grafts and functional
      results were satisfactory. The photooxidized mushroom shaped osteochondral
      transplants may be a suitable type of graft for functional results in cartilage
      resurfacing if stable anchorage of the grafts can be achieved.

PMID- 16971998
TI  - The role of negative intra-articular pressure in the maintenance of shoulder
      joint stability in dogs.
AB  - The objective of this study was to evaluate the effect of negative intra
      articular pressure on shoulder joint stability in canine cadavers. Cadaver
      forelimbs from 12 mature dogs were used. The forelimbs were placed in a testing
      frame and axially preloaded with 4 kg of weight. Shoulder joint stability was
      tested in flexion, extension, and neutral position before and after venting of
      the joint capsule. Humeral translation relative to the glenoid was induced by
      applying a 3 kg load in three different directions (cranial, lateral, and medial)
      and quantitatively measured by use of an electromagnetic motion tracking system.
      Peak translational data were compared in each joint position before and after
      venting of the joint capsule. After venting the shoulder joint capsule, a
      significant increase in translation was observed in the cranial direction with
      the joint in neutral position and in the medial direction with the joint in
      extension. The horizontal translations measured after venting of the joint
      capsule were likely not clinically relevant. Negative intra-articular pressure is
      not a major contributor to shoulder stability in dogs during weight-bearing.

PMID- 16971999
TI  - Detailed preoperative planning for fracture treatment with Ilizarov method in
      three dogs.
AB  - The purpose of this study is to present preoperative planning with consideration
      of the anatomical variations of different dog breeds, gross anatomy, preoperative
      radiographs and computed tomography (CT) images, ring number, ring type and ring
      levels, rod positions and rod number for fracture treatment using the Ilizarov
      method in three dogs. In all cases, preoperative radiographs of affected limb and
      contralateral limb, intact extremity's CT views and anatomical atlases were used
      for preoperative frame planning. The frame is assembled preoperatively, rehearsed
      and then it is applied. Preoperative radiographs and clinical findings of
      affected limbs are beneficial for preoperative frame planning, whilst CT views
      are not as they do not provide any different vision of anatomical structures for
      all cases. Other colleagues' and our anatomical atlases, including cross
      sectional views of limbs, are satisfactory for preoperative planning. In
      addition, functional and cosmetical results in all three cases were determined to
      be very good.

PMID- 16972000
TI  - Complications and radiographic findings following cemented total hip replacement:
      a retrospective evaluation of 97 dogs.
AB  - Cemented total hip replacement (cTHR) is commonly performed to treat intractable
      coxofemoral pain in dogs. While owners generally perceive a good outcome after
      the procedure, the longevity of the implant may be limited by complications such
      as infection and aseptic loosening. The objective of this retrospective study was
      to identify the prevalence of complications and radiographic changes following
      cTHR, and to identify factors that may predispose to a need for revision surgery.
      Medical records and radiographs from 97 dogs that underwent cTHR were evaluated
      for signalment, preoperative degree of osteoarthritis, technical errors, intra
      operative culture results, and the post-operative radiographic appearance of the
      implant. The complications occurring in the intra-operative and short-term
      (<eight week) periods, and the radiographic appearance of the implant in the long
      term (>eight week) time period were recorded. Mean (+/- SD) follow-up time was
      1.1 +/- 1.6 years (range: 0-7.7 years). Seven dogs had a short-term complication
      and a revision surgery was performed in eleven dogs. Osseous or cement changes
      were radiographically detectable in the majority of cTHR. Eccentric positioning
      of the femoral stem and the presence of radiolucent lines at the femoral cement
      bone interface were positively associated with the occurrence of revision
      surgery. The clinical significance of the periprosthetic radiographic changes is
      unclear and further investigation is warranted.

PMID- 16972001
TI  - Surgical repair of a tibial fracture in a Belgian Landrace pig.
AB  - This paper reports the surgical treatment of a tibial fracture in a castrated
      adult male Belgian Landrace pig of 180 kg. The fracture was repaired using an
      intramedullary Steinmann pin, combined with cerclage wire and external
      transfixation. In contrast to other animal species, the fracture repair in the
      pig was hindered by the short and curved bones, the thick subcutaneous fat layer
      and the pronounced musculature. Postoperatively, the pig developed an
      osteomyelitis of the tibia due to pin tract contamination. Despite this
      complication, the fracture healed acceptably when all fixation material was
      removed two months after surgery. The infection resolved quickly and a
      satisfactory clinical result was obtained.

PMID- 16972002
TI  - Fractures combination of the proximal antebrachium in an immature dog that
      resembles Monteggia fracture.
AB  - A 5-month-old German shepherd dog with a combination of a proximal radial physeal
      fracture and a proximal ulnar diaphyseal comminuted fracture, with cranial
      displacement of their distal fragment, was presented. This fractures combination
      resembles type I Monteggia fracture. After surgical reduction of the fractures,
      three full-cerclage wires were used to stabilize the ulnar fracture, and two
      positional screws were placed across the radius and ulna immediately distally to
      the growth plate to hold these bones in apposition. Four weeks post-operatively,
      the screws were removed since sufficient callus had been formed and the dog was
      free of lameness. It seems that if the appropriate conditions for a type I
      Monteggia fracture develop in an immature dog, proximal radial physeal fracture
      instead of radial head luxation may accompany ulnar diaphyseal fracture.

PMID- 16972003
TI  - A case of invertebral disc degeneration and prolapse with Schmorl's node
      formation in a sheep.
AB  - A Schmorl's node is the herniation of nucleus pulposus through the cartilaginous
      end plate of the vertebral disc into the body of the adjacent vertebra. Their
      formation is relatively common in people, and they may be symptomatic or
      asymptomatic. In contrast, there are few reported cases of Schmorl's nodes in non
      human animals. This report describes a case of thoracic intervertebral disc
      degeneration, with Schmorl's node formation in a sheep.

PMID- 16972004
TI  - An extract of Polygonum multiflorum protects against free radical damage induced
      by ultraviolet B irradiation of the skin.
AB  - Over the last decades, the incidence of ultraviolet B (UVB)-related skin problems
      has been increasing. Damages induced by UVB radiation are related to mutations
      that occur as a result of direct DNA damage and/or the production of reactive
      oxygen species. We investigated the anti-oxidant effects of a Polygonum
      multiflorum thumb extract against skin damage induced by UVB irradiation. Female
      SKH-1 hairless mice were divided into three groups: control (N = 7), distilled
      water- (N = 10), and P. multiflorum extract-treated (PM, N = 10) groups. The PM
      (10 g) was extracted with 100 mL distilled water, cryo-dried and 9.8 g was
      obtained. The animals received a topical application of 500 microL distilled
      water or PM extract (1, 2, 4, 8, and 16%, w/v, dissolved in distilled water) for
      30 min after UVB irradiation (wavelength 280-320 nm, 300 mJ/cm(2); 3 min) of the
      dorsal kin for 14 days, and skin immunohistochemistry and Cu,Zn-superoxide
      dismutase (SOD1) activity were determined. SOD1 immunoreactivity, its protein
      levels and activities in the skin were significantly reduced by 70% in the
      distilled water-treated group after UVB irradiation compared to control. However,
      in the PM extract-treated groups, SOD1 immunoreactivity and its protein and
      activity levels increased in a dose-dependent manner (1-16%, w/v, PM extract)
      compared to the distilled water-treated group. SOD1 protein levels and activities
      in the groups treated with 8 and 16%, w/v, PM extract recovered to 80-90% of the
      control group levels after UVB. These results suggest that PM extract strongly
      inhibits the destruction of SOD1 by UV radiation and probably contains anti-skin
      photoaging agents.

PMID- 16972005
TI  - Inducing mutations in the mouse genome with the chemical mutagen
      ethylnitrosourea.
AB  - When compared to other model organisms whose genome is sequenced, the number of
      mutations identified in the mouse appears extremely reduced and this situation
      seriously hampers our understanding of mammalian gene function(s). Another
      important consequence of this shortage is that a majority of human genetic
      diseases still await an animal model. To improve the situation, two strategies
      are currently used: the first makes use of embryonic stem cells, in which one can
      induce knockout mutations almost at will; the second consists of a genome-wide
      random chemical mutagenesis, followed by screening for mutant phenotypes and
      subsequent identification of the genetic alteration(s). Several projects are now
      in progress making use of one or the other of these strategies. Here, we report
      an original effort where we mutagenized BALB/c males, with the mutagen
      ethylnitrosourea. Offspring of these males were screened for dominant mutations
      and a three-generation breeding protocol was set to recover recessive mutations.
      Eleven mutations were identified (one dominant and ten recessives). Three of
      these mutations are new alleles (Otop1mlh, Foxn1sepe and probably rodador) at
      loci where mutations have already been reported, while 4 are new and original
      alleles (carc, eqlb, frqz, and Sacc). This result indicates that the mouse
      genome, as expected, is far from being saturated with mutations. More mutations
      would certainly be discovered using more sophisticated phenotyping protocols.
      Seven of the 11 new mutant alleles induced in our experiment have been localized
      on the genetic map as a first step towards positional cloning.

PMID- 16972006
TI  - Polymorphism of the promoter region and exon 1 of the CTLA4 gene in endemic
      pemphigus foliaceus (fogo selvagem).
AB  - Endemic pemphigus foliaceus (EPF) is an autoimmune bullous skin disease
      characterized by acantholysis and antibodies against a desmosomal protein,
      desmoglein 1. Genetic and environmental factors contribute to development of this
      multifactorial disease. HLA class II and some cytokine gene polymorphisms are the
      only genetic markers thus far known to be associated with susceptibility to or
      protection from EPF. The cytotoxic T-lymphocyte antigen-4 gene (CTLA4) encodes a
      key immunoreceptor molecule that regulates and inhibits T-cell proliferation. It
      participates in the regulatory process controlling autoreactivity and therefore
      has been considered a strong candidate gene in autoimmune diseases. In the search
      for genes that might influence EPF pathogenesis, we analyzed variants of the
      CTLA4 gene in a sample of 118 patients and 291 controls from a Brazilian
      population. This is the first study investigating the possible role of
      polymorphisms of the 2q33 chromosomal region in differential susceptibility to
      pemphigus foliaceus. Promoter region and exon 1 single nucleotide polymorphisms 
      318 (C,T) and 49 (A,G) were genotyped using sequence-specific oligonucleotide
      probes after amplification by the polymerase chain reaction. The allelic and
      genotypic frequencies did not differ significantly between the patient and the
      control groups (-318T: 9.8 and 10.9%, 49G: 33.0 and 35.2% were the allelic
      frequencies in patients and controls, respectively). In addition, no significant
      difference was found when the patient and control population samples were
      stratified by the presence of HLA-DRB1 alleles. We conclude that the CTLA4 -318
      (C,T) and 49 (A,G) polymorphisms do not play a major role in EPF development.

PMID- 16972007
TI  - Computerized invasive measurement of time-dependent intraocular pressure.
AB  - Several methods have been described to measure intraocular pressure (IOP) in
      clinical and research situations. However, the measurement of time varying IOP
      with high accuracy, mainly in situations that alter corneal properties, has not
      been reported until now. The present report describes a computerized system
      capable of recording the transitory variability of IOP, which is sufficiently
      sensitive to reliably measure ocular pulse peak-to-peak values. We also describe
      its characteristics and discuss its applicability to research and clinical
      studies. The device consists of a pressure transducer, a signal conditioning unit
      and an analog-to-digital converter coupled to a video acquisition board. A
      modified Cairns trabeculectomy was performed in 9 Oryctolagus cuniculus rabbits
      to obtain changes in IOP decay parameters and to evaluate the utility and
      sensitivity of the recording system. The device was effective for the study of
      kinetic parameters of IOP, such as decay pattern and ocular pulse waves due to
      cardiac and respiratory cycle rhythm. In addition, there was a significant
      increase of IOP versus time curve derivative when pre- and post-trabeculectomy
      recordings were compared. The present procedure excludes corneal thickness and
      error related to individual operator ability. Clinical complications due to
      saline infusion and pressure overload were not observed during biomicroscopic
      evaluation. Among the disadvantages of the procedure are the requirement of
      anesthesia and the use in acute recordings rather than chronic protocols.
      Finally, the method described may provide a reliable alternative for the study of
      ocular pressure dynamic alterations in man and may facilitate the investigation
      of the pathogenesis of glaucoma.

PMID- 16972008
TI  - Credentialing imaging informatics professionals: creation of items for the CIIP
      examination.

PMID- 16972009
TI  - Creating an IHE ATNA-based audit repository.
AB  - Compliance with the Health Insurance Portability and Accountability Act (HIPAA)
      requires gathering audit information from picture archiving and communications
      systems (PACS) regarding evidence trails of human interactions. Until recently,
      most PACS users have had limited access to auditing information. Access required
      resources to handle manual inspection of audit logs, and access to proprietary
      databases was not always available. Some vendors now produce eXtensible Markup
      Language (XML) audit logs based on certain events occurring in PACS. However, it
      is up to the user to convert this information into an easily mined data
      repository supporting compliance and quality control. This process can be handled
      in multiple ways, which could mean different audit mechanisms depending on the
      PACS (or other hospital system) used. It is apparent that an organized method of
      dealing with audit information is needed. This help may be provided within the
      Integrating the Healthcare Environment (IHE) framework. The IHE initiative
      defines a set of profiles, actors, and transactions that create common scenarios
      for particular workflow processes. The Integration Profiles depict security as a
      fundamental requirement of the framework. Specifically, the Audit Trail and Node
      Authentication (ATNA) profile defines standards based mechanisms for securely
      transmitting and storing audit records in a central repository. The data
      structure defined by the profile provides a number of record types that capture
      different audit events. A general feasibility study for storing currently
      available PACS audit information following the profile is defined, and steps to
      an automated solution are discussed.

PMID- 16972010
TI  - Use of a thin-section archive and enterprise 3D software for long-term storage of
      thin-slice CT data sets.
AB  - Rapid advances are changing the technology and applications of multidetector
      computed tomography (CT) scanners. The major increase in data associated with
      this new technology, however, breaks most commercial picture archiving and
      communication system (PACS) architectures by preventing them from delivering data
      in real time to radiologists and outside clinicians. We proposed a phased model
      for 3D workflow, installed a thin-slice archive and measured thin-slice data
      storage over a period of 5 months. A mean of 1,869 CT studies were stored per
      month, with an average of 643 images per study and a mean total volume of 588
      GB/month. We also surveyed 48 radiologists to determine diagnostic use,
      impressions of thin-slice value, and requirements for retention times. The
      majority of radiologists thought thin slice was helpful for diagnosis and
      regularly used the application. Permanent storage of thin slice CT is likely to
      become best practice and a mission-critical pursuit for the health care
      enterprise.

PMID- 16972011
TI  - Correlation of PET/CT standardized uptake value measurements between dedicated
      workstations and a PACS-integrated workstation system.
AB  - PURPOSE: This study was conducted to evaluate the clinical utility of a Positron
      Emission Tomography/Computed Tomography (PET/CT) analysis module of a picture
      archiving communication system (PACS) workstation in comparison to a dedicated
      PET/CT interpretation workstation. MATERIALS AND METHODS: The study included 32
      consecutive patients referred for an [(18)F] Fluro-2-Deoxy-D: -Glucose ((18)F
      FDG) PET/CT at our institution. Images were reviewed at dedicated PET/CT and at
      PACS-integrated workstations. Mean standardized uptake values (SUVs) were
      calculated for the liver and the lung. Maximum SUVs were recorded for the bladder
      and an index lesion with the highest FDG uptake. The time spent for SUV
      measurements was recorded. Correlation of the SUV measurements was calculated
      with the Pearson coefficient. RESULTS: Pearson coefficients between the
      workstations ranged from 0.96 to 0.99 for bladder and lesion maximum SUVs. For
      liver and lung average SUVs, the coefficients varied from 0.53 to 0.98. The mean
      time spent to perform the four SUV measurements was 122.6 s for the dedicated
      workstations and 134.6 s for the PACS-integrated system. CONCLUSION: The
      correlation of SUV measurements between dedicated PET/CT and PACS-integrated
      workstations is very good, especially for maximum SUVs. For routine reading of
      PET/CT scans, a PACS workstation with a PET/CT analysis module offers an
      excellent alternative to the use of a dedicated PET/CT workstation.

PMID- 16972012
TI  - Star Trek Meets the Operating Room: Nurse Scotty, Beam Me Up-A Tricorder.

PMID- 16972013
TI  - Structure based studies of the adaptive diversification process of congerins.
AB  - The isoforms of a fish galectin, congerins I and II, have several features that
      make them suitable for a study of accelerated process of molecular
      diversification based on 3D structures: They have been generated by a gene
      duplication, and still maintain 47% amino acid sequence identity to each other.
      Their genes show very high K A: /K S: ratio, and are though to be components of
      fish defense system. The crystal systems for a high-resolution analysis are known
      for both proteins. A series of works with biochemistry, molecular biology, and X
      ray crystallography techniques have suggested that the two proteins might have
      evolved under differential selection pressures. Congerin I appeared to be a
      stabilized version of galectin-1. Congerin II was shown to be adapted to a new
      carbohydrate-ligand. The 3D structures of the wild type and mutant proteins have
      revealed the probable cause and consequence of the selection pressure responsible
      for the diversification of congerins.

PMID- 16972014
TI  - Molecular diversity and evolution of the Siglec family of cell-surface lectins.
AB  - Sialic acids are a family of acidic sugars with a 9-carbon backbone, prominently
      expressed in animals of deuterostome lineage. Siglecs are the largest family of
      vertebrate endogenous receptors that recognize glycoconjugates containing sialic
      acids. Although a few Siglecs are well-conserved throughout vertebrate evolution
      and show similar binding preference regardless of the species of origin, most
      others, particularly the CD33-related subfamily of Siglecs, show marked inter
      species differences in repertoire, sequence, and binding preference. The
      diversification of CD33-related Siglecs may be driven by direct competition
      against pathogens, and/or by necessity to catch up with the changing landscape of
      endogenous glycans, which may in turn be changing to escape exploitation by other
      pathogens.

PMID- 16972015
TI  - Molecular and functional diversity of vascular endothelial growth factors.
AB  - Members of the vascular endothelial growth factor (VEGF) family are crucial
      regulators of neovascularization and are classified as cystine knot growth
      factors that specifically bind cellular receptor tyrosine kinases VEGFR-1, VEGFR
      2, and VEGFR-3 with high but variable affinity and selectivity. The VEGF family
      has recently been expanded and currently comprises seven members: VEGF-A, VEGF-B,
      placenta growth factor (PlGF), VEGF-C, VEGF-D, viral VEGF (also known as VEGF-E),
      and snake venom VEGF (also known as VEGF-F). Although all members are
      structurally homologous, there is molecular diversity among the subtypes, and
      several isoforms, such as VEGF-A, VEGF-B, and PlGF, are generated by alternative
      exon splicing. These splicing isoforms exhibit differing properties, particularly
      in binding to co-receptor neuropilins and heparin. VEGF family proteins play
      multiple physiological roles, such as angiogenesis and lymphangiogenesis, while
      exogenous members (viral and snake venom VEGFs) display activities that are
      unique in physiology and function. This review will highlight the molecular and
      functional diversity of VEGF family proteins.

PMID- 16972016
TI  - The role of osteocytes and bone microstructure in preventing osteoporotic
      fractures.
AB  - The skeleton alters its geometry following trauma, the introduction of artificial
      defects and of fatigue-induced microcracks. The precise mechanism by which the
      skeleton adapts remains unclear. Microcracks might directly affect the cell by
      damaging the osteocyte cell network or causing apoptosis. Bone microstructure may
      play an important role in these processes by diverting and arresting propagating
      microcracks and so prevent fracture failure. This paper discusses the effects of
      microstructure on propagating cracks, how microdamage may act as a stimulus for
      bone adaptation and its potential effects on bone biochemistry.

PMID- 16972017
TI  - Reduced loading due to spinal-cord injury at birth results in "slender" bones: a
      case study.
AB  - INTRODUCTION: The present case study compared bone density, bone geometry and
      muscle cross-sectional area (CSA) in a male who sustained spinal-cord injury
      (SCI) at birth (from here called SCI-B) with two matched controls without SCI,
      and also with four individuals with SCI of similar level and injury completeness
      but sustained at age 15 or greater. METHODS: All subjects with SCI were at least
      3 years post-injury and had experienced motor incomplete lesions at the cervical
      level. Computed tomography was used to measure volumetric bone density, indices
      of bone strength [CSA and maximum, minimum and polar area moments of inertia (I
      (max), I (min), I (pol))] and muscle CSA at the tibia (66% of tibia length,
      measured proximally from the distal end). RESULTS: Lower leg muscle CSA of SCI-B
      was 63+/-6% of values in non-SCI controls, and 72+/-12% of values in other males
      with SCI. In SCI-B, bone CSA was roughly half (52+/-4%) that of non-SCI controls
      and 73+/-16% of bone CSA values in other males with SCI. The magnitudes of the
      area moment of inertia variables (I (max), I (min), and I (pol)) in SCI-B were
      approximately 25% of control values. Further, the moment of inertia variables in
      SCI-B were 27-54% of values obtained in other males with SCI, indicating that
      experiencing SCI in the early stages of life has a remarkable impact on bone
      shape. Interestingly, tibia bone density did not appear to be affected; the
      average difference in bone density between SCI-B and non-SCI controls was -1.2+/
      0.7%. The bone densities of other males with SCI were 4-19% lower than in SCI-B.
      CONCLUSIONS: Muscle atrophy and bone loss are commonly reported consequences of
      SCI. This case reveals that important changes in bone geometry occur after SCI,
      and that mechanical loading during growth plays a vital role in the development
      of bone size and shape.

PMID- 16972018
TI  - Vanishing finger in psoriatic arthritis: a case report.
AB  - Dactylitis is a typical phenomenon in psoriatic arthritis, presenting as a
      "sausage-shaped" finger. Although classically the distal interphalangeal joints
      are affected, proximal interphalangeal joints and metacarpophalangeal joints are
      frequently involved. We present a patient who presented with severe psoriatic
      arthritis of the proximal interphalangeal joint, leading to subtotal
      disappearance of the phalangeal bones and important shortening of the fourth
      finger after 10 years of evolution.

PMID- 16972019
TI  - Elevated levels of soluble Fas (APO-1, CD95), soluble Fas ligand, and matrix
      metalloproteinase-3 in sera from patients with active untreated adult onset
      Still's disease.
AB  - To investigate serum levels of soluble Fas (sFas), soluble Fas ligand (sFas-L),
      and matrix metalloproteinase-3 (MMP-3) in patients with active untreated adult
      onset Still's disease (AOSD). Serum levels of sFas, sFas-L, and MMP-3 were
      determined by enzyme-linked immunosorbent assays in 20 patients with active
      untreated AOSD, 20 patients with active rheumatoid arthritis (RA), and 20 healthy
      controls. Linear regression was used to evaluate the correlation between clinical
      activity scores and serum levels of sFas, sFas-L, and MMP-3 in AOSD patients.
      Significantly higher levels of sFas, sFas-L, and MMP-3 in sera were found in
      active untreated AOSD patients compared to healthy controls. Serum levels of
      sFas, sFas-L, and MMP-3 correlated well with clinical activity scores of AOSD
      patients (r=0.467, 0.694, and 0.798, respectively). There was a significant
      correlation between CRP values and serum levels of sFas-L as well as MMP-3
      (r=0.583 and r=0.582, respectively, both p<0.01), and a positive correlation
      between serum sFas-L levels and serum MMP-3 levels (r=0.726, p<0.001) in AOSD
      patients. Significantly higher levels of serum sFas-L were found in AOSD patients
      than in RA patients. Serum levels of sFas, sFas-L, and MMP-3 fluctuated and were
      found to be parallel to disease activity of AOSD. sFas, sFas-L, and MMP-3, which
      were significantly elevated in sera of active untreated AOSD patients and
      paralleled disease activity, may be involved in the pathogenesis of this disease.
      Further studies are needed to determine the pathophysiologic role of sFas, sFas
      L, and MMP-3 in AOSD.

PMID- 16972020
TI  - Association of estrogen receptor alpha gene polymorphisms and lifestyle factors
      with calcaneal quantitative ultrasound and osteoporosis in postmenopausal
      Vietnamese women.
AB  - Genetic and lifestyle factors are important in the pathogenesis of osteoporosis.
      We investigated the relationships of PvuII and XbaI polymorphisms of the estrogen
      receptor alpha (ER-alpha) gene, lifestyle factors with speed of sound at the
      calcaneus (calcaneal SOS) and osteoporosis in a population-based study of 140
      healthy postmenopausal women. By an analysis of covariates, women with higher
      copies of P or X alleles had higher calcaneal SOS compared with others (P=0.012,
      PP vs. pp; P=0.045, Xx vs. xx). Women with lower copies of px or higher copies of
      PX haplotypes had higher calcaneal SOS compared with others (P=0.021, 0 px vs. 2
      px; P=0.011, 1 PX vs. 0 PX). The px and PX haplotypes, age and years since
      menopause were found to be independent predictors of calcaneal SOS in multiple
      linear regression models. Using logistic regression, we found an increased
      osteoporosis risk with evidence for a px haplotype dose effect (OR=2.82, 95%
      CI=1.50-5.31, P=0.001) and for a PX haplotype dose effect (OR=0.42, 95% CI=0.19
      0.93, P=0.033). An increased educational level was associated with a reduced risk
      of osteoporosis (P=0.035 in the model with px, P=0.044 in the model with PX). In
      conclusion, the present study suggests that PvuII and XbaI polymorphims of the ER
      alpha gene, age, years since menopause and educational level are associated with
      bone density, as assessed by calcaneal SOS, and osteoporosis in postmenopausal
      Vietnamese women.

PMID- 16972021
TI  - Prediction of systemic exposure to cyclosporine in Japanese pediatric patients.
AB  - The monitoring of the blood concentration at 2 h (C(2)) after the oral
      administration of a cyclosporine (CsA) microemulsion was reconfirmed to be useful
      for the prediction of systemic exposure, the area under the blood concentration
      time curve from 0 to 4 h (AUC(0-4)), in a group of Japanese patients, consisting
      of 33 children aged 5-15 years and 19 young adults aged 16-27 years, with a
      greater correlation for C(2) (r = 0.927) than the trough concentration (r =
      0.488). The dose-normalized AUC(0-4) was independent of gender or indications for
      CsA, while it depended on body size, i.e., the age (P = 0.065) and total body
      weight (P = 0.026). MDR1 C3435T had a weak, but insignificant effect (P = 0.072);
      it was about 22-31% lower in the patients with TT(3435). Co-administration of a
      steroid and further treatment with nifedipine had a more intensive effect (P =
      0.018); co-administration resulted in a 51% increase in the dose-normalized AUC(0
      4). A strong effect was also observed for the serum total cholesterol level (P =
      0.001). Collectively, the discrepancies in the results on MDR1 C3435T among
      investigators might be due to variability in the age/total body weight, co
      administration drugs or serum lipid level.

PMID- 16972022
TI  - New RB1 oncogenic mutations and intronic polymorphisms in Serbian retinoblastoma
      patients: genetic counseling implications.
AB  - The purpose of this work was to identify germ line RB1 mutations in 16 Serbian
      retinoblastoma patients for genetic counselling. Mutation analysis was carried
      out by PCR directed sequencing of the 27 exons. Loss of heterozygosity for two
      RB1 intragenic markers was also analyzed in 14 tumour samples. Five new RB1
      oncogenic mutations (g.2078 del C, g.77047_48 del GC, g.78117_8 del TT, g.160797
      del T, and g.64439+2 T>C) and two recurrences (R445X and Q383X) have been found
      in this study. In addition, four intronic variants were observed germ line in
      some unilateral patients. Two of these variants (g.44668-15T/G, and g.166204
      8T/A) are discussed as potential oncogenic mutation candidates. The results show
      the relevance of studies aimed to investigate the role of intronic variants in
      exon splicing regulation. Such studies will help to disclose hidden
      retinoblastoma susceptibilities, important for accurate genetic counselling.

PMID- 16972023
TI  - Molecular epidemiology of mtDNA mutations in 903 Chinese families suspected with
      Leber hereditary optic neuropathy.
AB  - We report the molecular epidemiology of three primary mutations in mitochondrial
      DNA (mtDNA) responsible for Leber hereditary optic neuropathy (LHON) based on
      analysis of probands suspected with LHON from 903 Chinese families. Most of them
      had optic neuropathy of unknown cause, and only 128 had a family history of optic
      neuropathy. Mutations in the mtDNA were detected in 346 probands. Of the 346
      cases, 340 were homoplasmic and only six were heteroplasmic; 284 were male and 62
      were female; 120 had a family history and 226 were sporadic. G11778A, T14484C and
      G3460A mutations were detected in 312 (90.2%), 30, and four families,
      respectively. The majority (226/346, 65.3%) of all LHON cases in Chinese are
      sporadic. These 226 probands (29.2%) were identified from 775 probands with
      sporadic optic neuropathy. Affected male-to-female ratio was 4.6:1 for all
      probands but was 2.2:1 for family members. Average age at onset was 18.5 years,
      ranging from 4.5 to 47 years old.

PMID- 16972024
TI  - Role of the nitric oxide pathway in ischemia-reperfusion injury in isolated
      perfused guinea pig lungs.
AB  - We examined the role of the nitric oxide (NO) pathway on ischemia-reperfusion
      injury via the use of isolated perfused guinea pig lungs. We administered both L
      Arginine and N-nitro-L-arginine methyl ester (L-NAME) to the lungs in or after 3
      h of ischemia. We observed pulmonary artery pressures as well as tissue and
      perfusate malondialdehyde (MDA) and glutathione (GSH) levels. We observed that L
      NAME significantly increased both tissue and perfusate GSH levels and pulmonary
      artery pressures, but it decreased both tissue and perfusate MDA levels. On the
      other hand, L-arginine significantly decreased pulmonary artery pressure and both
      tissue and perfusate glutathione levels, but it increased both tissue and
      perfusate MDA levels. Electron microscopic evaluation supported our findings by
      indicating the preservation of lamellar bodies of type II pneumocytes. We
      concluded that L-NAME administration during reperfusion improves lung recovery
      from ischemic injury.

PMID- 16972025
TI  - Review: molecular evolution and the feasibility of an avian influenza virus
      becoming a pandemic strain--a conceptual shift.
AB  - During recent years, a conceptual shift took place with respect to the genetic
      dynamics of influenza A viruses. In difference of the widely accepted approach
      that avian viral strains have the capacity to infect man only after undergoing
      genetic reassortment within pigs, it is now contended that direct transfection of
      man by intact avian-harbored viral genotypes is an actual, recurrent move, which
      may bring bout the generation of a new pandemic strain. This cardinal conceptual
      shift has been propelled by the appearance in 1997 of the zoonotic avian
      influenza H5N1 virus--a virulent, not yet contagious strain for humans--and
      ostensibly followed a genuine, unprecedented path within the evolutionary
      paradigm of Influenza A virus. This paper suggests that direct avian-human
      genetic interface is a pristine fundamental within the natural history of this
      protean pathogen, points at earlier as well as corroborative findings leading to
      such postulation, and regards the course of the H5N1 virus (and alike), as a
      readily detectable and traceable one, presently, rather then a novel development
      It further examines the general feasibility of various components of that
      interface at large, such that give rise--whether gradually or abruptly--to
      pandemic genotypes, in terms of infectivity, pathogenicity and contagiousness.
      Within that context, the anticipated involvement of certain human-adapted
      antigenic subtypes is referred to, extrapolatively. Connectedly, the significance
      of natural ice as plausible regenerator of influenza A viruses, and its possible
      contribution to the emergence and reemergence of pandemic strains are
      accentuated.

PMID- 16972026
TI  - Genome comparison of a novel classical swine fever virus isolated in China in
      2004 with other CSFV strains.
AB  - The genome of a novel classical swine fever virus (CSFV), SWH/CA/2004, isolated
      from a hog pen in Henan Province, central China, is 12,296 nucleotides (nt) in
      length. It is composed of a 373-nt 5' terminal non-translated region (NTR), a
      11,697-nt open reading frame (ORF) encoding a polyprotein of 3,898 amino acids
      (aa), and a 226-nt 3'-NTR. Genome comparison of the SWH/CA/2004 isolate (GenBank
      Accession: DQ127910) with other known CSFV isolates was performed and analyzed.
      Corresponding segments from SWH/CA/2004 and other reported strains shared 80.4
      99.8% identity at the nucleotide level and 89.5-99.8% identity at the amino acid
      level. From an evolutionary point of view, isolate SWH/CA/2004 is closely related
      to the highly virulent isolate cF114/CA/2001, with a pairwise distance of 0.013;
      and distantly related to the moderately virulent isolate GXWZ02/CA/2003, with
      pairwise distance 0.170. The phylogenetic trees of the full-length genome and the
      following region E(rns), E1, E2, and NS5B-based neighbor-joining (NJ) method were
      constructed and approximately divided into different genetic groups according to
      avirulence, moderate virulence and high virulence, while other region-based NJ
      trees demonstrated sequence conservation between these groups. The four genomic
      regions may constitute important criteria for genetic typing of diverse CSFV
      isolates. Based on these analyses, isolate SWH/CA/2004 was deduced to belong to
      the highly virulent isolate group. However, SWH/CA/2004 also contains a 14-U
      deletion in the 3'-NTR that is characteristic of avirulent isolates. These
      analyses constitute a comprehensive study of the phylogenetics of CSF based on
      distinct regions of the genome and may provide the basis for future molecular
      epidemiology research to identify virulent strain outbreaks and trigger
      implementation of appropriate control measures.

PMID- 16972027
TI  - Genetic characterization of VP3 gene of group A rotaviruses.
AB  - We sequenced VP3 gene of four rotavirus strains and examined the diversity of VP3
      and its other genetic characteristics in a total of 22 Group A rotaviruses. The
      22 rotavirus strains were derived from six different host species (human, avian,
      bovine, equine, simian and porcine). Comparison of the partial VP3 peptide
      sequences (aa 141-294) showed identities ranging from 49 to 99% among different
      species. The phylogenetic analysis of VP3 sequences revealed segregation
      according to the species origin. This was further confirmed by identification of
      three host specific domains within the VP3 peptide. Thus, the host range
      restriction or attenuation previously shown to associate with VP3 may be
      attributed to the species-specific nature of the gene.

PMID- 16972028
TI  - Identification of a B-cell antigenic epitope at the N-terminus of SARS-CoV M
      protein and characterization of monoclonal antibody against the protein.
AB  - To identify the potential B-cell antigenic epitopes within the N-terminus of SARS
      CoV (SARS-associated coronavirus, SARS-CoV) M protein and characterize monoclonal
      antibody (MAb) against the protein as well as its recognizing region, we
      expressed and purified a portion of SARS-CoV M protein (amino acid 1-43) in
      Escherichia coli (E. coli). By using Western blot and enzyme-linked immunosorbent
      assay (ELISA), we showed that the purified recombinant M protein could be
      recognized by four SARS-CoV-positive human sera even when those sera were 12,800
      fold diluted. Furthermore, we characterized one representative IgG2 MAb, 3H9,
      which exhibited a strong immunoreaction to both recombinant M protein and native
      viral protein of SARS-CoV. We found a B-cell antigenic epitope located between
      amino acid 1-15 and defined the MAb recognizing region within amino acid 16-28 of
      M. These findings not only suggest that both recombinant M protein and its
      specific MAbs may be used as the diagnostic reagents for SARS, but also provide a
      potential target site for the design of an epitope-based vaccine against SARS.

PMID- 16972029
TI  - Genetic variability in the sapovirus capsid protein.
AB  - Sapovirus (SV), which causes gastroenteritis in humans, is composed of
      genetically divergent viruses classified into 5 genogroups. In this study, 2.2-kb
      nucleotide sequences of the 3' terminus of the genome of 15 SV strains detected
      in Japan were determined. The 15 SV strains could be classified into four
      genogroups (GI, GII, GIV and GV), and in two of these, GI and GII, 10 genotypes
      were identified. The amino acid sequences of the central variable region of the
      capsid protein showed less than 81% identity when strains belonging to different
      genotypes were compared. It was therefore supposed that antigenic variety exists
      between different genotypes. These results will be useful for further genetic and
      antigenic analyses of SV.

PMID- 16972030
TI  - Reactivation from quiescence does not coincide with a global induction of herpes
      simplex virus type 1 transactivators.
AB  - Herpes simplex virus type 1 (HSV-1) reactivates from a small fraction of latently
      infected neurons in vivo and neuronally differentiated (ND), quiescently infected
      (QIF)-PC12 cells in vitro. This may be the result of reactivation initiating in
      only a few cells, or reactivation followed by premature termination of the
      productive virus life cycle in many or even a majority of cells. To examine the
      viral stress response, HSV-1 promoters of representative alpha, beta, and gamma
      class genes were examined in ND- and QIF-PC12 cells after treatments with agents
      known to induce reactivation. HSV-1 promoters displayed variable levels of basal
      gene expression in ND-PC12 cells ranging from 2 to 1,200 times the level of the
      control vector pGL3-Basic. Expression of the latency associated transcript (LAT)
      was greatest, with representatives of the alpha class exhibiting greater
      expression than the beta and gamma classes. The HSV-1 promoters examined did not
      respond dramatically to stress treatments. The viral gene response was also
      measured during the initiation of reactivation of a cryptic HSV-1 genome after
      forskolin treatment, under conditions that restricted DNA replication. During the
      first 24 h after stress induction the response was limited. By 48 h post
      forskolin treatment, only modest increases occurred for ICP0, ICP4, and LAT
      transcripts, reaching levels of no greater than 2.2 times mock treated levels. In
      contrast, ICP27, ribonucleotide reductase (RR), and VP16 promoters did not
      respond. These findings indicate that reactivation from QIF-PC12 cells does not
      result in a global response of the specific HSV-1 genes tested, when assessed at
      the population level. These data support the hypothesis that stress-induced
      reactivation initiates in a minority of cells.

PMID- 16972031
TI  - Regions of importance for interaction of puumala virus nucleocapsid subunits.
AB  - Puumala virus (PUUV) is a hantavirus that causes a mild form of hemorrhagic fever
      with renal syndrome in northern and central Europe, and in large parts of Russia.
      The nucleocapsid (N) protein encoded by hantaviruses plays an important role in
      the life-cycle of these viruses, and one important function for the N-protein is
      to oligomerize, surround and protect the viral RNAs. We have identified amino-
      and carboxy-terminal regions involved in PUUV N-N interactions, which comprise
      amino acids 100-120 and 330-405. Our findings strengthen the hypothesis that the
      amino-terminus of the N-protein of hantaviruses holds a more regulatory function
      regarding N-N interactions, while conserved residues in the carboxy-terminal
      region, F335 together with F336 and W392, in concert with Y388 and/or F400 seems
      to play a more critical role in the PUUV N-N formation. This study provides
      evidence that the amino-terminal regions involved in the N-N interaction of
      Puumala virus are similar to those reported for Seoul virus (SEOV) and to some
      extent Hantaan virus (HTNV), even though the identity between PUUV N and
      SEOV/HTNV N is markedly lower than between PUUV N and Tula virus (TULV) N or Sin
      Nombre virus (SNV) N.

PMID- 16972032
TI  - Comparative sequence analysis of US28 gene of human cytomegalovirus strains
      isolated from HIV-positive patients.
AB  - Human Cytomegalovirus (HCVM) encodes several G-protein coupled receptors, such as
      US28 protein. We determined the US28 gene sequence from clinical isolates
      obtained from 17 Human Immunodeficiency Virus (HIV)-infected patients with HCMV
      infection. Two types of clinical specimens were collected: peripheral blood
      leucocytes (PBLs) from 12 patients with HCMV-positive viremia and cerebro-spinal
      fluids (CSF) from five patients with HCMV-encephalitis. Comparison of US28
      nucleotide sequences between clinical specimens and several HCMV reference
      strains showed that mutations were clustered at both ends of the gene. The
      mutations observed at the C-terminus were observed at some sequences whereas the
      mutations observed at the N-terminus lead us to define five patterns of
      mutations. These patterns were equally distributed among isolates obtained from
      CSF or PBLs of HIV-infected patients. For each clinical isolate, the gB genotype
      was determined. There was no genetic association between gB genotype and US28
      patterns. The comparison of the results of the present study and those published
      from sequences obtained from children with HCMV congenital disease (Arav-Boger,
      2002) demonstrates that two motifs appear especifically either in US28 protein
      sequences obtained from HIV-positive patients (motif 4) or in US28 protein
      sequences obtained from patients with congenital HCMV infection (motif 5/genotype
      B). The appearance of these patterns of mutations in other clinical context needs
      to be studied.

PMID- 16972033
TI  - Detection of unusual mutation within the VP1 region of different re-isolates of
      poliovirus Sabin vaccine.
AB  - In the present study, a genomic analysis of full VP1 sequence region of 15
      clinical re-isolates (14 healthy vaccinees and one bone marrow tumor patient) was
      conducted, aiming to the identification of mutations and to the assessment of
      their impact on virus fitness, providing also insights relevant with the natural
      evolution of Sabin strains. Clinical re-isolates were analyzed by RT-PCR,
      sequencing and computational analysis. Some re-isolates were characterized by an
      unusual mutational pattern in which non-synonymous mutations outnumbered the
      synonymous ones. Furthermore, the majority of amino-acid substitutions were
      located in the capsid exterior, specifically in N-Ags, near N-Ags and in the
      north rim of the canyon. Also mutations, which are well-known determinants of
      attenuation, were identified. The results of this study propose that some re
      isolates are characterized by an evolutionary pattern in which non-synonymous
      mutations with a direct phenotypic impact on viral fitness are fixed in viral
      genomes, in spite of synonymous ones with no phenotypic impact on viral fitness.
      Results of the present retrospective characterization of Sabin clinical re
      isolates, based on the full VP1 sequence, suggest that vaccine-derived viruses
      may make their way through narrow breaches and may evolve into transmissible
      pathogens even in adequately immunized populations. For this reason increased
      poliovirus laboratory surveillance should be permanent and full VP1 sequence
      analysis should be conducted even in isolates originating from healthy vaccinees.

PMID- 16972034
TI  - Genetic characterization of a new mammalian reovirus, type 2 Winnipeg (T2W).
AB  - We previously described isolation of a potentially new reovirus strain from the
      central nervous system of an 8-week-old female infant with a history of active
      varicella, oral thrush, hypoalbuminemia, intermittent fevers, diarrhea and
      feeding intolerance [Hermann et al., Ped. Inf. Dis J. 23, 373 (2004)]. This
      reovirus strain was tentatively identified as a member of the serotype 2 group by
      virus neutralization and RNA-gel electrophoresis studies and has been named type
      2 Winnipeg (T2W). For this study we determined the nucleotide sequences of the
      T2W S1, S2, S3 and S4 genome segments to allow molecular comparison with other
      reoviruses. Comparative segment alignments of T2W S1 gene sequence with other
      reovirus S1 sequences showed T2W belongs to reovirus serotype 2. T2W S1 is most
      similar to the S1 genes of reovirus strains T2/Human/Netherlands/1,984 and
      T2/Human/Netherlands/1,973 with nucleotide identity >93%. The T2W S2 gene showed
      highest identity to reovirus T1 Lang S2 (approximately 75%). The T2W S3 gene
      showed highest identity to the S3 gene of T3/Human/Netherlands/1,983
      (approximately 74%), and the T2W S4 gene showed highest identity to the T2 Jones
      S4 gene (approximately 73%). Pairwise protein comparisons between T2W sigma
      proteins and all available reovirus sigma proteins ranged from <21% identity for
      the sigma1 comparisons to more than 95% identity for sigma2 comparisons. The
      predicted T2W sigma1, sigma2 and sigma3 protein sequences were confirmed by mass
      spectrometry.

PMID- 16972035
TI  - Analysis of the genetic and the corresponding antigenic variability of the VP1 3'
      end of ECHO virus type 11 and ECHO virus type 30.
AB  - The enteroviruses (EV), RNA viruses belonging to the Picornaviridae family, have
      a high genetic variability due to the absence of the efficient proofreading and
      post replicative repair activities associated with the RNA polymerase. In the
      present work, we studied the genetic and the antigenic variability of ECHO virus
      types 11 (E11) and 30 (E30), which are the most isolated echoviruses serotypes in
      clinical and environmental samples. We established on the 3' end of the VP1 gene,
      consensus sequences of E11 and E30 by alignment of 67 E11 and 247 E30 published
      sequences in GenBank. Our results of sequences comparison showed that the
      majority of the mutational sites are situated on the third nucleotide of the
      codon. These mutations were without consequence on the antigenic sequences of the
      VP1 protein. Thus, E11 and E30 have a high genetic variability (1/3 of the
      nucleotides are variable), but a relative antigenic conservation. The analysis of
      the intertypic antigenic variability between E11 and E30 was obtained by the
      alignment of the corresponding amino acids sequences relative to the N-terminal
      part of the VP1 protein. Two discriminating parts were highlighted, probably
      representing antigenic sites for neutralisation antibodies.

PMID- 16972036
TI  - Comparative analysis of the prion protein gene sequences in African lion.
AB  - The prion protein gene of African lion (Panthera Leo) was first cloned and
      polymorphisms screened. The results suggest that the prion protein gene of eight
      African lions is highly homogenous. The amino acid sequences of the prion protein
      (PrP) of all samples tested were identical. Four single nucleotide polymorphisms
      (C42T, C81A, C420T, T600C) in the prion protein gene (Prnp) of African lion were
      found, but no amino acid substitutions. Sequence analysis showed that the higher
      homology is observed to felis catus AF003087 (96.7%) and to sheep number M31313.1
      (96.2%) Genbank accessed. With respect to all the mammalian prion protein
      sequences compared, the African lion prion protein sequence has three amino acid
      substitutions. The homology might in turn affect the potential intermolecular
      interactions critical for cross species transmission of prion disease.

PMID- 16972037
TI  - Cloning and sequence analysis of the N gene of porcine epidemic diarrhea virus
      LJB/03.
AB  - The nucleocapsid (N) gene of the porcine epidemic diarrhea virus (PEDV) strain
      LJB/03 which was previously isolated in Heilongjiang province, China, was cloned,
      sequenced and compared with published sequences of other avian and mammalian
      coronavirus. The nucleotide sequence encoding the entire N gene open reading
      frame (ORF) of LJB/03 was 1326 bases long and encoded a protein of 441 amino
      acids with predicted Mr of 49 kDa. It consisted of 405 adenines (30.5%), 294
      cytosines (22.1%), 329 guanines (24.8%) and 298 thymines (22.5%) residues.
      Sequence comparison with other PEDV strains selected from GenBank revealed that
      the LJB/03 N gene has a high sequence homology to those of other PEDV isolates,
      97.4% with JS2004, 95.6% with chinju99, 96.6% with Br1/87, and 96.8% with CV777.
      The encoded protein shared 96.4% amino acid identities compared with CV777, 96.1%
      with Brl/87, 98% with JS2004, 96.90% with chinju99, respectively. The amino acid
      sequence contained seven potential protein kinase C phosphorylation sites, nine
      Casein kinase II phosphorylation sites, one Tyrosine kinase phosphorylation site,
      two cAMP- and cGMP-dependent protein kinase phosphorylation sites.

PMID- 16972038
TI  - Characterization of the genes encoding UL24, TK and gH proteins from duck
      enteritis virus (DEV): a proof for the classification of DEV.
AB  - Duck enteritis virus (DEV) is classified to the family Herpesviridae, but has not
      been grouped into any genus so far. Four overlapped fragments were amplified from
      the DEV genome with polymerase chain reaction (PCR). The assembled length of the
      four fragments was 6,202 bp, which contained the genes encoding unique long (UL)
      24, thymidine kinase (TK) and glycoprotein H (gH) proteins. The UL24 overlapped
      with TK by 64 nucleotides (nt), in a head-to-head transcription orientation, and
      the TK and gH had the same transcription orientation. The comparison of amino
      acid sequences of these 3 deduced DEV proteins with other 12 alphaherpesviruses
      displayed 5 highly conserved sites in the UL24, as well as another 5 consensus
      regions in the TK and 4 consensus regions in the gH. The RNA polymerase II
      transcriptional control elements were identified in all the UL24, TK and gH of
      DEV. These elements included core promoters, TATA motifs and polyadenylation
      sites. Phylogenetic analysis for the genetic classification of DEV in the
      Alphaherpesvirinae subfamily with other 12 alphaherpesviruses was computed. The
      result showed that DEV was more closely related to avian herpesviruses, except
      infectious laryngotracheitis virus (ILTV), than to other alphaherpesviruses.
      Conclusively, according to the phylogenesis-based analysis and the homology
      comparison of functional domains of UL24, TK and gH, DEV should be classified to
      a separate genus of the Alphaherpesvirinae subfamily in the family Herpesviridae.

PMID- 16972039
TI  - Characterization of a new Puumala virus genotype associated with hemorrhagic
      fever with renal syndrome.
AB  - Hantavirus serotype Puumala (PUUV) is the etiologic agent of Nephropathia
      epidemica (NE), a mild variant of Hemorrhagic Fever with Renal Syndrome (HFRS) in
      Europe, with lethality rates up to 1% among human patients. The serotype PUUV is
      composed of numerous geographically restricted strains forming a great number of
      phylogeographic lineages, sublineages, variants, and clusters. We describe a new,
      geographically and phylogenetically well-defined pathogenic PUUV sublineage in
      Southwest Germany (strain Heidelberg/hu) originated from an HFRS patient. The
      genetic analysis of PUUV strain Heidelberg/hu may contribute in future to better
      diagnostics, the development of vaccines, and the understanding of the factors
      that determine hantavirus pathogenesis.

PMID- 16972041
TI  - Respiratory syncytial virus(RSV)-induced allergy may be controlled by IL-4 and
      CX3C fractalkine antagonists and CpG ODN as adjuvant: hypothesis and implications
      for treatment.
AB  - Based on the hypothesis that respiratory syncytial virus (RSV) sG protein causes
      allergy in patients, it is suggested that treatment of RSV patients with
      antagonists of IL-4 and FKN early in infection will prevent the increased level
      of IL-4 in the serum. Together with CpG ODNs that induce Toll-like receptor 9(+)
      (TLR9(+)) plasmacytoid dendritic cells to release type I IFN-alpha and -beta will
      reactivate the inhibited Th1 cells and the antiviral cytotoxic T leukocytes. In
      addition, binding of CpG ODNs to TLR9(+) B cells will stop IgE synthesis and
      antiviral IgG and IgA will continue. Together, the IL-4 and FKN antagonists and
      CpG ODNs reactivate the adaptive immune response to clear the virus and protect
      the patient from a second RSV infection. It is also suggested that the less
      pathogenic RSV strain Long may be a candidate for vaccine development after
      deletion of the FKN and superantigen domains from the G gene.

PMID- 16972040
TI  - Respiratory syncytial virus (RSV) evades the human adaptive immune system by
      skewing the Th1/Th2 cytokine balance toward increased levels of Th2 cytokines and
      IgE, markers of allergy--a review.
AB  - Infection of infants in their first year of life, children and elderly people
      with the respiratory syncytial virus (RSV) endangers the life of the patient. An
      attempt to develop a formalin-inactivated RSV (FI-RSV) vaccine during the 1960s
      resulted in an aggravated infection in immunized children, leading to
      hospitalization, while infection of non-immunized children produced much milder
      symptoms. The reason for this remained an enigma, one which was gradually solved
      over the last decade by many researchers who studied the molecular biology of RSV
      infection of respiratory ciliary cells. Clinical studies of RSV-infected patients
      indicated increased levels of Th2 cytokines and IgE in the patients' sera,
      suggesting that an allergy-like condition developed during infection. The
      biomarkers of allergy caused by endogenous or environmental allergens include a
      marked increase of the Th2 cytokine IL-4 and IgE non-neutralizing antibodies to
      the allergen. The way allergens trigger allergy was deciphered recently, and will
      be discussed later. Studies of RSV infection led to the suggestion that RSV
      patients suffer from allergy prior to RSV infection, a concept that was later
      abandoned. Studies on HIV-1 [Y. Becker, Virus Genes 28, 319-331 (2005)] research
      led me to the hypothesis that since HIV-1 infection induces a marked increase of
      IL-4 and IgE in serum, an allergy-like condition, the AIDS stage is the result of
      an allergen motif that is embedded in the shed viral gp120 molecules. It is
      hypothesized that the viral-soluble G glycoprotein (sG) contains a T cell
      superantigen (Tsag) that is capable of binding to the V(H)3 domain of
      IgE/FcepsilonRI(+) hematopoietic cells, basophils, mast cells and monocytes,
      similar to the case of allergens, and that this aggregation causes these innate
      system cells to degranulate and release large amounts of Th2 cytokines (IL-4, IL
      5, IL-10, IL-13) into the blood. The way these Th2 cytokines skew the Th1/Th2
      balance toward Th2 > Th1 will be discussed. The aim of the present review is to
      base RSV pathogenicity on the numerous very good analyses of the virus genes and
      to suggest a therapeutic approach to treatment that is directed at preventing the
      inhibitory effects of Th2 cytokines on the adaptive immune system of the
      patients, instead of inhibiting RSV replication by antivirals. The review of the
      molecular research on the role of the viral fusion (F) and attachment (G)
      glycoproteins of RSV provided information on their role in the virus infection:
      early in infection the F glycoprotein induces Th1 cells to release the Th1
      cytokines IL-2, IL-12 and IFN-gamma to activate precursors CTLs (pCTLs) to become
      anti-RSV CTLs. The G and sG glycoproteins attach to FKNR1(+) ciliary respiratory
      epithelial cells as well as directly to eosinophils to the lungs. The sG T cell
      antigen can also induce the release of large amounts of Th2 cytokines from CD4(+)
      T cells and from FCepsilonRI(+) mast cells, basophils and monocytes. By
      comparison to HIV-1 gp120 it is possible to show that in the G and sG proteins
      the T cell antigen resembles the CD4(+) T cell superantigen (=allergen) domain of
      HIV-1 gp120 which aggregates with IgE/FCepsilonRI(+) hematopoietic cells. The
      increased IL-4 level in the serum inhibits the adaptive immune response: IL
      4Ralpha(+) Th1 cells stop Th1 cytokine synthesis and IL-4Ralpha(+) B cells stop
      the synthesis of antiviral IgG and IgA and switch to IgE synthesis. In addition,
      the hematopoietic cells release histamine and prostaglandin which induce
      wheezing. The gradual increase of sG molecules creates a gradient of fractalkine
      (FKN) which directs IL-5-activated eosinophils to the lungs of the patient.

PMID- 16972044
TI  - Predicting impaired glucose metabolism in women with polycystic ovary syndrome by
      decision tree modelling.
AB  - AIMS/HYPOTHESIS: Polycystic ovary syndrome (PCOS) is a risk factor of type 2
      diabetes. Screening for impaired glucose metabolism (IGM) with an OGTT has been
      recommended, but this is relatively time-consuming and inconvenient. Thus, a
      strategy that could minimise the need for an OGTT would be beneficial. MATERIALS
      AND METHODS: Consecutive PCOS patients (n=118) with fasting glucose <6.1 mmol/l
      were included in the study. Parameters derived from medical history, clinical
      examination and fasting blood samples were assessed by decision tree modelling
      for their ability to discriminate women with IGM (2-h OGTT value >/=7.8 mmol/l)
      from those with NGT. RESULTS: According to the OGTT results, 93 PCOS women had
      NGT and 25 had IGM. The best decision tree consisted of HOMA-IR, the
      proinsulin:insulin ratio, proinsulin, 17-OH progesterone and the ratio of
      luteinising hormone:follicle-stimulating hormone. This tree identified 69 women
      with NGT. The remaining 49 women included all women with IGM (100% sensitivity,
      74% specificity to detect IGM). Pruning this tree to three levels still
      identified 53 women with NGT (100% sensitivity, 57% specificity to detect IGM).
      Restricting the data matrix used for tree modelling to medical history and
      clinical parameters produced a tree using BMI, waist circumference and WHR.
      Pruning this tree to two levels separated 27 women with NGT (100% sensitivity,
      29% specificity to detect IGM). The validity of both trees was tested by a leave
      10%-out cross-validation. CONCLUSIONS/INTERPRETATION: Decision trees are useful
      tools for separating PCOS women with NGT from those with IGM. They can be used
      for stratifying the metabolic screening of PCOS women, whereby the number of
      OGTTs can be markedly reduced.

PMID- 16972045
TI  - Do known risk factors explain the higher coronary heart disease mortality in
      South Asian compared with European men? Prospective follow-up of the Southall and
      Brent studies, UK.
AB  - AIMS/HYPOTHESIS: We examined prospectively whether measured risk factors can
      explain the higher CHD mortality in South Asians compared with Europeans.
      MATERIALS AND METHODS: Conventional CHD risk factors and those associated with
      insulin resistance were measured in 1,787 European and 1,420 South Asian men aged
      40 to 69 years at baseline in the population-based Southall and Brent studies
      (London) between 1988 and 1990. Participants were followed up for mortality.
      RESULTS: By February 2006, there were 202 CHD deaths (108 Asian, 94 European).
      South Asian men had double the CHD mortality of European men in Cox regression
      analyses adjusted for age, smoking, and cholesterol (hazard ratio [HR] 2.14, 95%
      CI 1.56-2.94, p<0.001). Nearly half of all South Asian CHD deaths versus 13% of
      deaths among Europeans were among persons with diabetes. Asian men had greater
      CHD mortality than Europeans, both in the with- and the without-diabetes
      categories at baseline. CHD mortality remained significantly higher in South
      Asian men in multivariable models that adjusted for conventional risk factors and
      diabetes and/or impaired glucose regulation, features of insulin resistance, or
      the metabolic syndrome (HR 1.6-1.9). Accounting for co-morbidity and socio
      economic status did not materially alter the findings.
      CONCLUSIONS/INTERPRETATION: These data confirm that South Asian men have
      significantly higher CHD mortality than their European counterparts, while
      indicating that neither conventional risk factors, nor insulin resistance
      parameters or metabolic syndrome criteria as currently defined can account for
      this excess risk. The contribution of unmeasured factors to the elevated vascular
      risk in South Asians should be addressed in future studies.

PMID- 16972047
TI  - Nutlet morphology and anatomy of the genus Lycopus (Lamiaceae: Mentheae).
AB  - Nutlet morphology and pericarp structure of 16 species in the genus Lycopus were
      studied by light microscopy (LM) and scanning electron microscopy (SEM), and a
      detailed description of nutlet morphological features for all examined taxa is
      provided. The nutlets of all taxa in the genus Lycopus are well adapted to
      typical hydrochory (or nautochory) with an air-filled pericarp, and myxocarpy was
      not at all found. It is noteworthy that the nutlet morphology (in particular the
      shape of corky crests and corky ring and the distribution of glandular trichomes)
      and pericarp anatomy of Lycopus are unique and are well distinguished from the
      other genera in the tribe Mentheae. We also found some groups of the species
      within the genus Lycopus by the present nutlet morphological and anatomical data
      that appear to be useful as diagnostic characteristics for delineation purposes
      at the specific/interspecific levels. The earlier infrageneric classification for
      the genus Lycopus is, however, not well supported by the present results. In
      addition, the systematic and biological implications of the nutlet
      characteristics investigated are briefly discussed.

PMID- 16972046
TI  - Cloning and expression of a cytochrome P450 hydroxylase gene from Amycolatopsis
      orientalis: hydroxylation of epothilone B for the production of epothilone F.
AB  - Degenerate PCR primers were used to amplify cytochrome P450 gene fragments from
      the high-GC gram-negative bacteria Amycolatopsis orientalis, which catalyzes the
      hydroxylation of epothilone B to produce epothilone F. The amplified fragments
      were used as hybridization probes to identify and clone two intact cytochrome
      P450 genes. The expression of one of the cloned genes in a Streptomyces lividans
      transformant resulted in the biotransformation of epothilone B to epothilone F.
      The conversion of epothilone B to epothilone F by the S. lividans transformant
      was confirmed by mass spectrometry and nuclear magnetic resonance spectroscopy.

PMID- 16972048
TI  - Visceral heterotaxia with polysplenia syndrome and haemorrhagic splenic
      infarction as a rare cause of the acute paediatric abdomen.

PMID- 16972049
TI  - Radiological evaluation with Doppler sonography and multidetector CT angiography
      in congenital hepatic arteriovenous malformation in a newborn.
AB  - Although hepatic arteriovenous malformations are rarely reported, they frequently
      have life-threatening complications such as cardiac failure and are associated
      with a high mortality rate. Consequently, accurate prenatal and early postnatal
      diagnosis is important and therapeutic procedures depend on the imaging features.
      We report the early postnatal sonographic, Doppler sonographic, multidetector CT
      and CT angiography findings of a congenital hepatic arteriovenous malformation in
      a newborn.

PMID- 16972050
TI  - Hypertrophy with unilateral resistance exercise occurs without increases in
      endogenous anabolic hormone concentration.
AB  - We aimed to gain insight into the role that the transitory increases in anabolic
      hormones play in muscle hypertrophy with unilateral resistance training. Ten
      healthy young male subjects (21.8 +/- 0.4 years, 1.78 +/- 0.04 m, 75.6 +/- 2.9
      kg; mean +/- SE) engaged in unilateral resistance training for 8 week (3
      days/week). Exercises were knee extension and leg press performed at 80-90% of
      the subject's single repetition maximum (1RM). Blood samples were collected in
      the acute period before and after the first training bout and following the last
      training bout and analyzed for total testosterone, free-testosterone, luteinizing
      hormone, sex hormone binding globulin, growth hormone, cortisol, and insulin-like
      growth factor-1. Thigh muscle cross sectional area (CSA) and muscle fibre CSA by
      biopsy (vastus lateralis) were measured pre- and post-training. Acutely, no
      changes in systemic hormone concentrations were observed in the 90 min period
      following exercise and there was no influence of training on these results.
      Training-induced increases were observed in type IIx and IIa muscle fibre CSA of
      22 +/- 3 and 13 +/- 2% (both P < 0.001). No changes were observed in fibre CSA in
      the untrained leg (all P > 0.5). Whole muscle CSA increased by 5.4 +/- 0.9% in
      the trained leg (P < 0.001) and remained unchanged in the untrained leg (P =
      0.76). Isotonic 1RM increased in the trained leg for leg press and for knee
      extension (P < 0.001). No changes were seen in the untrained leg. In conclusion,
      unilateral training induced local muscle hypertrophy only in the exercised limb,
      which occurred in the absence of changes in systemic hormones that ostensibly
      play a role in muscle hypertrophy.

PMID- 16972051
TI  - Significance of MHC class II haplotypes and IgG Fc receptors in SLE.
AB  - Systemic lupus erythematosus (SLE) is a systemic antibody-mediated autoimmune
      disease that develops under the control of multiple susceptibility genes. Genetic
      studies in murine and human SLE have identified several chromosomal intervals
      that contain candidate susceptibility genes. However, the ultimate identification
      of the genes and their roles in disease process need much further investigation.
      Spontaneous murine SLE models provide useful tools in this respect. In this
      chapter, we show this line of investigation, particularly focusing on the roles
      of major histocompatibility complex (MHC) class II and immunoglobulin G Fc
      receptors (FcgammaRs). The existence of high-affinity autoantibodies is evidence
      that autoimmunity in SLE is antigen-driven. Thereby, MHC class II haplotypes have
      been implicated in SLE susceptibility; however, because of the linkage
      disequilibrium that exists among the class I, II and III genes within the MHC
      complex, it has been difficult to discriminate the relative contributions of
      individual loci. On the other hand, the extent of antibody synthesis upon antigen
      stimulation and associated inflammatory cascades are controlled in several ways
      by the balance of stimulatory and inhibitory signaling molecules on immune cells.
      Stimulatory/inhibitory FcgammaRs mediate one such mechanism, and there are
      reports indicating the association between polymorphic FcgammaRs and SLE.
      However, as stimulatory and inhibitory FcgammaRs cluster on the telomeric
      chromosome 1, the absolute contribution of individual genes has been difficult to
      dissect. In studies of genetic dissection using interval-congenic and intragenic
      recombinant mouse strains of SLE models, we show evidence and discuss how and to
      what extent MHC class II molecules and stimulatory/inhibitory FcgammaRs are
      involved in SLE susceptibility.

PMID- 16972053
TI  - Raman spectroscopic analysis of human remains from a seventh century cist burial
      on Anglesey, UK.
AB  - Specimens from human remains exhibiting unusual preservation excavated from a
      seventh century stone cist burial at Towyn y Capel in Anglesey, UK, have been
      analysed using Raman spectroscopy with near-infrared laser excitation at 1,064
      and 785 nm. Specimens of hair and bone provided evidence for severe degradation
      and microbial colonisation. The deposits within the stone cist showed that some
      microbially mediated compounds had been formed. Analysis of crystals found at the
      interface between the hair and the skeletal neck vertebrae revealed a mixture of
      newberyite and haematite, associated with decomposition products of the hair and
      bone. An interesting differential degradation was noted in the specimens analysed
      which could be related to the air-void and the presence of plant root inclusions
      into the stone cist. This is the first time that Raman spectroscopy has been used
      in the forensic archaeological evaluation of burial remains in complex and
      dynamic environments.

PMID- 16972054
TI  - In vitro nonenzymatic glycation of DNA nucleobases: an evaluation of advanced
      glycation end products under alkaline pH.
AB  - The advanced glycation end products (AGEs) of DNA nucleobases have received
      little attention, perhaps due to the fact that adenine, guanine, cytosine and
      thymine do not dissolve under mild pH conditions. To maintain nucleobases in
      solution, alkaline pH conditions are typically required. The objectives of this
      investigation were twofold: to study the susceptibility of DNA nucleobases to
      nonenzymatic attack by different sugars, and to evaluate the factors that
      influence the formation of nucleobase AGEs at pH 12, i.e., in an alkaline
      environment that promotes the aldo-keto isomerization and epimerization of
      sugars. Varying concentrations of adenine, guanine, thymine and cytosine were
      incubated over time with constant concentrations of D-glucose, D-galactose or D/L
      glyceraldehyde under different conditions of temperature and ionic strength.
      Incubation of the nucleobases with the sugars resulted in a heterogeneous
      assembly of AGEs whose formation was monitored by UV/fluorescence spectroscopy.
      Capillary electrophoresis and HPLC were used to resolve the AGEs of the DNA
      adducts and provided a powerful tool for following the extent of glycation in
      each of the DNA nucleobases. Mass spectrometry studies of DNA adducts of guanine
      established that glycation at pH 12 proceeded through an Amadori intermediate.

PMID- 16972052
TI  - Genetics of SLE in mice.
AB  - Genetic studies in spontaneous, induced, and gene-manipulated mouse models of SLE
      have provided significant insights into the potential number and diversity of
      genes that can promote, resist, and modify lupus susceptibility. Novel genes and
      mechanisms of disease pathogenesis have also been identified. Importantly, mouse
      models have provided an initial view of the genomic landscape of lupus-affecting
      genes, and have documented the complexities of verifying and determining the role
      of specific candidate loci and genes. Mouse models of lupus should continue to
      serve as a vital approach to defining the genetics of SLE.

PMID- 16972055
TI  - Development of a supercritical fluid extraction-gas chromatography-mass
      spectrometry method for the identification of highly polar compounds in secondary
      organic aerosols formed from biogenic hydrocarbons in smog chamber experiments.
AB  - A new one-step method for the analysis of highly polar components of secondary
      organic aerosols (SOA) has been developed. This method should lead to a better
      understanding of SOA formation and evolution since it enables the compounds
      responsible for SOA formation to be identified. Since it is based on
      supercritical fluid extraction coupled to gas chromatography-mass spectrometry,
      it minimizes the analysis time and significantly enhances sensitivity, which
      makes it suitable for trace-level compounds, which are constituents of SOA. One
      of the key features of this method is the in situ derivatisation step: an online
      silylation allowing the measurement of highly polar, polyfunctional compounds,
      which is a prerequisite for the elucidation of chemical mechanisms. This paper
      presents the development of this analytical method and highlights its ability to
      address this major atmospheric issue through the analysis of SOA formed from the
      ozonolysis of a biogenic hydrocarbon (sabinene). Ozonolysis of sabinene was
      performed in a 6 m3 Teflon chamber. The aerosol components were derivatised in
      situ. More than thirty products, such as sabinaketone, sabinic acid and other
      multifunctional compounds including dicarboxylic acids and oxoacids, were
      measured. Nine of them were identified and quantified. The sensitivity and the
      linearity (0.91<R<0.98) of the method were both good and detection limits ranged
      from 1.2 to 6.4 ng for the investigated compounds.

PMID- 16972056
TI  - Development of a multianalyte method for the determination of anabolic hormones
      in bovine urine by isotope-dilution GC-MS/MS.
AB  - A sensitive, specific and selective multianalyte GC-MS/MS method has been
      developed for the determination of 11 anabolic hormones in bovine urine. After
      adjusting the urine pH to 4.8, the samples were spiked with deuterated internal
      standards and submitted to enzymatic hydrolysis with beta
      glucuronidase/arylsulfatase. Hormones were eluted with methanol through a C18
      solid phase cartridge and submitted to a liquid-liquid extraction. Analytes were
      derivatized by adding N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) with 1%
      trimethylchlorosilane and GC-MS data were obtained in the positive electron
      impact tandem mass mode. Under these conditions, no matrix effects were observed
      and limit of detection values were in the range of 0.005 ng/mL
      (diethylstilbestrol) to 0.38 ng/mL (17alpha-methyltestosterone and 17alpha
      ethynylestradiol). Recoveries from 81% (alpha-zeranol) to 149% (17alpha
      methyltestosterone) were found under the selected conditions. These results were
      better than those found using heptafluorobutyric anhydride (HFBA) as derivative
      reagent and those measured in full scan and selective ion monitoring modes.

PMID- 16972057
TI  - Simultaneous determination of five synthetic antioxidants in edible vegetable oil
      by GC-MS.
AB  - A simple, quick and nontoxic analytical method for the simultaneous determination
      of five synthetic antioxidants [t-butyl-4-hydroxyanisole (BHA), 2,6-di-t-butyl
      hydroxytoluene (BHT), t-butyl hydroquinone (TBHQ), ethoxyquin (EQ) and 2,6-di
      tert-butyl-4-hydroxymethyl-phenol (Ionox 100)] in edible vegetable oil has been
      developed. The analytes were extracted by ethanol, then separated and detected by
      GC-MS. Extraction conditions such as volume of ethanol required, mixing time and
      number of extractions were investigated and optimized by an orthogonal array
      experimental design. The five compounds behaved linearly in the 0.100
      approximately 20.0 mg/L concentration range, and the limits of detection (LOD)
      for BHA, BHT, TBHQ, EQ and Ionox-100 were 1.00, 0.92, 11.5, 0.83 and 1.39
      microg/L, respectively. The recoveries at the tested concentrations of 1.00, 20.0
      and 100 mg/kg were 75.6 approximately 123%, with coefficients of variation<10.0%.
      The proposed procedure was successfully applied to the simultaneous analysis of
      the five antioxidants in soybean oil, tea oil, edible blended oil, rap oil,
      peanut oil, peanut blended oil and sesame oil samples purchased from local
      supermarkets.

PMID- 16972058
TI  - Isolated avulsion of the biceps femoris insertion-injury patterns and treatment
      options: a case report and literature review.
AB  - Isolated avulsion of the biceps femoris tendon is a relatively rare condition. We
      report a case of a 43 year-old soccer player with a rupture of the biceps femoris
      tendon which occurred in a hyperextension of the knee. Based on this case, we
      discuss the literature referring to injury pattern and treatment.

PMID- 16972059
TI  - Long-term results of 58 hip cup revision arthroplasties using a threaded ring
      implant.
AB  - INTRODUCTION: There is still a discussion whether cementless hip cup revisions
      should be performed with a press fit cup or a threaded ring implant. MATERIALS
      AND METHODS: The results of 58 hip cup changes using the spherical, threaded ring
      "Munich" are presented. In 16 cases, the ring "Munich I" with a smooth surface
      and in 42 cases the ring "Munich II" with a corundum-blasted surface were
      implanted. Mean follow-up was 7.5 years; radiological signs of loosening and the
      Harris Hip Score were examined. RESULTS: The re-revision rate for aseptic
      loosening of the ring was 12/58 overall (Munich I: 5/16, Munich II: 7/42). The
      average Harris Hip Score was 76.2 overall (Munich I: 74.4, Munich II: 76.8).
      Higher survival rates were achieved with the "Munich II" ring due to improved
      construction details. CONCLUSION: These rates are still below those reported for
      press-fit cups, the technique described by Slooff or reinforcement rings.

PMID- 16972060
TI  - Genetic analysis of the cultivated potato Solanum tuberosum L. Phureja Group
      using RAPDs and nuclear SSRs.
AB  - The Solanum tuberosum L. Phureja Group consists of potato landraces widely grown
      in the Andes from western Venezuela to central Bolivia, and forms an important
      breeding stock due to their excellent culinary properties and other traits for
      developing modern varieties. They have been distinguished by short-day
      adaptation, diploid ploidy (2n = 2x = 24), and lack of tuber dormancy. This
      nuclear simple sequence repeat (nSSR or microsatellite) study complements a prior
      random amplified polymorphic DNA (RAPD) study to explore the use of these markers
      to form a core collection of cultivar groups of potatoes. Like this prior RAPD
      study, we analyzed 128 accessions of the Phureja Group using nuclear
      microsatellites (nSSR). Twenty-six of the 128 accessions were invariant for 22
      nSSR markers assayed. The nSSR data uncovered 25 unexpected triploid and
      tetraploid accessions. Chromosome counts of the 102 accessions confirmed these
      nSSR results and highlighted seven more triploids or tetraploids. Thus, these
      nSSR markers (except 1) are good indicators of ploidy for diploid potatoes in 92%
      of the cases. The nSSR and RAPD results: (1) were highly discordant for the
      remaining 70 accessions that were diploid and variable in nSSR, (2) show the
      utility of nSSRs to effectively uncover many ploidy variants in cultivated
      potato, (3) support the use of a cultivar-group (rather than a species)
      classification of cultivated potato, (4) fail to support a relationship between
      genetic distance and geographic distance, (5) question the use of any single type
      of molecular marker to construct core collections.

PMID- 16972061
TI  - H22, a major resistance gene to the Hessian fly (Mayetiola destructor), is mapped
      to the distal region of wheat chromosome 1DS.
AB  - H22 is a major resistance gene conferring high-level of antibiosis to Hessian fly
      [Mayetiola destructor (Say)] larvae. It was previously assigned to wheat
      chromosome 1D through monosomic analysis (Raupp et al. in J Hered 84:142-145,
      1993). The objective of this study was to identify molecular markers that can be
      used for marker-assisted selection for wheat breeding, and to further map this
      gene toward map-based cloning. Forty-five simple sequence repeat (SSR) and
      sequence-tagged site (STS) markers specific to chromosome 1D were evaluated for
      linkage to H22 using a segregating population consisting of 192 F(2:3) families,
      which were derived from the cross Tugela-Dn1 x KS85WGRC01(H22). The STS Xhor2kv
      and SSR Xgdm33 are two flanking markers that are tightly linked to H22 at genetic
      distances of 0.3 and 1.0 cM, respectively. Five other SSR markers including
      Xgpw7082, Xwmc147, Xcfd15, Xwmc432 and Xwmc336 were also linked to H22 at the
      distance from 0.8 to 20.8 cM. Analysis of Chinese Spring (CS) deletion lines
      revealed that all the H22-linked markers are located distal to the breakpoint of
      del 1DS-5, indicating that the H22 gene is located at the distal 30% region on
      the short arm of wheat chromosome 1D. Genomic comparison suggested that the H22
      gene is located in the same or similar chromosomal region as the leaf rust
      resistance genes Lr21 and Lr40 on 1DS, and orthologous to the H9 gene cluster of
      1AS.

PMID- 16972062
TI  - Chinese herbal medicines and their efficacy in treating renal stones.
AB  - In herbal treatment of kidney stones, antilithics are used to "dissolve" the
      stones or aid their passing to guard against further retention. Diuretic action
      is also needed to increase the amount of fluid going through the kidneys and
      flush out the deposits. Previous clinical studies have shown that herbal
      medicines and their concoctions could be used to inhibit calcium oxalate
      crystallization. However, the pharmacodynamics and in-vitro effects of such
      medicines have not been established. Five Chinese herbal medicines were selected
      based on their usefulness in treating stone disease. A 96-well plate oxalate
      induced turbidity in artificial urine was used to evaluate the efficacies of the
      different herbal medicines on calcium oxalate crystallization. The metastable
      limit was determined and the nucleation rate was derived from 12-min time-course
      measurement of turbidity at 405 nm. Phase-contrast microscopy was used to
      visualize the crystals. The results showed that with increasing concentrations of
      herbal extracts, smaller calcium oxalate crystal sizes were observed. Overall,
      the five herbal medicinal extracts tested were able to promote nucleation of
      calcium oxalate crystals while at the same time decreasing the size. This in
      vitro crystallization confirms that prophylaxis of renal stones could be achieved
      by reducing overall supersaturation through promotion of small crystal nucleates
      and concomitant pharmacological diuretic action of herbal medicines. Clinical
      studies will provide more definitive conclusions.

PMID- 16972064
TI  - Absence of exendin-4 effects on postprandial glucose and lipids in the Gila
      monster, Heloderma suspectum.
AB  - Circulating nutrients serve as energy resources for functioning tissues
      throughout the body. While the tight regulation of plasma nutrients has been
      extensively studied in mammals, investigations into specific metabolic regulators
      in reptiles have been limited and have revealed conflicting results. The peptide
      exendin-4, which was isolated from the saliva of Gila monsters, Heloderma
      suspectum, has demonstrated prolonged plasma glucose-lowering properties in
      mammals. Although exendin-4 has often been labeled a venom protein, circulating
      plasma levels of exendin-4 have been shown to increase in response to feeding.
      Because exendin-4 has glucose-regulating effects in mammals, we hypothesized that
      post-prandial elevation in circulating exendin-4 levels in Gila monsters reduces
      plasma glucose and triglycerides. To examine the effect of exendin-4 on
      circulating nutrients, we measured plasma glucose, triglyceride, and cholesterol
      levels of Gila monsters in response to one of four treatments: fed live mice (a
      natural post-prandial increase in exendin-4), force-fed dead mice while
      anesthetized (no post-prandial exendin-4 increase), force-fed dead mice while
      anesthetized and injected with exendin-4 immediately after feeding (exogenous
      increase in exendin-4), and force-fed dead mice while anesthetized and injected
      with exendin-4 24 h after feeding (delayed exogenous increase in exendin-4).
      After prey ingestion, glucose and triglyceride levels increased significantly
      over time in all treatment groups, but there was no significant treatment effect.
      Plasma exendin-4 levels showed significant time and treatment effects, but did
      not correspond to glucose and triglyceride levels. Our results demonstrate that
      plasma nutrient levels in Gila monsters respond relatively slowly to feeding and
      that exendin-4 does not have the same effect on circulating glucose in Gila
      monsters as it does in mammals. Further studies are necessary to determine
      whether circulating exendin-4 has an alternate role in regulating other
      components of energy metabolism such as nutrient uptake rate in the small
      intestine.

PMID- 16972063
TI  - Biphasic characteristic of interactions between stiripentol and carbamazepine in
      the mouse maximal electroshock-induced seizure model: a three-dimensional
      isobolographic analysis.
AB  - The anticonvulsant effects produced by stiripentol (STP), carbamazepine (CBZ),
      and their combination in the maximal electroshock (MES)-induced seizures in mice
      were investigated using three-dimensional (3D) isobolographic analysis. With 3D
      isobolography, the combinations of both drugs at the fixed-ratios of 1:3, 1:1,
      and 3:1 for 16%, 50% and 84% antiseizure effects, respectively, were examined in
      order to evaluate the preclinical characteristics of the interactions between STP
      and CBZ. Additionally, to characterize precisely the types of interactions
      observed in the MES test, free plasma and total brain CBZ concentrations were
      estimated for all fixed-ratios tested. The 3D isobolographic analysis showed that
      STP and CBZ combined at the fixed-ratio of 1:3 produced supra-additive
      (synergistic) interactions in the MES test for the anticonvulsant effects ranging
      between 16% and 84%. In contrast, the combination of STP with CBZ at the fixed
      ratio of 3:1 exerted sub-additive (antagonistic) interactions in 3D isobolography
      for all antiseizure effects examined in the MES test. Only the combination of STP
      and CBZ at the fixed-ratio of 1:1 was additive for the investigated effects (16%,
      50% and 84%) in 3D isobolography. Pharmacokinetic evaluation of CBZ
      concentrations revealed that STP increased both free plasma and total brain CBZ
      concentrations for all fixed-ratio combinations tested (1:3, 1:1 and 3:1). In
      conclusion, the 3D isobolographic findings suggest that the combination of STP
      with CBZ exerted biphasic characteristics of interactions in the MES test,
      despite the pharmacokinetic increase in CBZ content in plasma and brains of
      experimental animals.

PMID- 16972065
TI  - The fission yeast Rpb4 subunit of RNA polymerase II plays a specialized role in
      cell separation.
AB  - RNA polymerase II is a complex of 12 subunits, Rpb1 to Rpb12, whose specific
      roles are only partly understood. Rpb4 is essential in mammals and fission yeast,
      but not in budding yeast. To learn more about the roles of Rpb4, we expressed the
      rpb4 gene under the control of regulatable promoters of different strength in
      fission yeast. We demonstrate that below a critical level of transcription, Rpb4
      affects cellular growth proportional to its expression levels: cells expressing
      lower levels of rpb4 grew slower compared to cells expressing higher levels.
      Lowered rpb4 expression did not affect cell survival under several stress
      conditions, but it caused specific defects in cell separation similar to sep
      mutants. Microarray analysis revealed that lowered rpb4 expression causes a
      global reduction in gene expression, but the transcript levels of a distinct
      subset of genes were particularly responsive to changes in rpb4 expression. These
      genes show some overlap with those regulated by the Sep1-Ace2 transcriptional
      cascade required for cell separation. Most notably, the gene expression signature
      of cells with lowered rpb4 expression was highly similar to those of mcs6, pmh1,
      sep10 and sep15 mutants. Mcs6 and Pmh1 encode orthologs of metazoan TFIIH
      associated cyclin-dependent kinase (CDK)-activating kinase (Cdk7-cyclin H-Mat1),
      while Sep10 and Sep15 encode mediator components. Our results suggest that Rpb4,
      along with some other general transcription factors, plays a specialized role in
      a transcriptional pathway that controls the cell cycle-regulated transcription of
      a specific subset of genes involved in cell division.

PMID- 16972066
TI  - Conformational stability and three-dimensional model of the delta-opioid
      pharmacophore for the extended antiparallel dimer structure of Met-enkephalin in
      water.
AB  - The conformational stability of the extended antiparallel dimer structure of Met
      enkephalin in water was analyzed by examining the hydration structure of
      enkephalin using molecular dynamics simulations. The result shows that, despite
      of the hydrophicility of the terminal atoms in the pentapeptide, the main
      contributor for the stability of the dimer in water is the four intermolecular
      hydrogen bonds between the Gly(2) and Phe(4) groups. The three-dimensional model
      of the delta-opioid pharmacophore for this dimer structure was also established.
      Such a model was demonstrated to match the delta-opioid pharmacophore query
      derived from the non-peptides SIOM, TAN-67, and OMI perfectly. This result thus
      strongly supports the assumption that the dimer structure of Met-enkephalin is a
      possible delta-receptor binding conformation.

PMID- 16972067
TI  - Percutaneous endoscopic lumbar discectomy for migrated disc herniation:
      classification of disc migration and surgical approaches.
AB  - Percutaneous endoscopic lumbar discectomy (PELD) for migrated disc herniations is
      technically demanding due to the absence of the technical guideline. The purposes
      of this study were to propose a radiologic classification of disc migration and
      surgical approaches of PELD according to the classification. A prospective study
      of 116 consecutive patients undergoing single-level PELD was conducted. According
      to preoperative MRI findings, disc migration was classified into four zones based
      on the direction and distance from the disc space: zone 1 (far up), zone 2 (near
      up), zone 3 (near down), zone 4 (far down). Two surgical approaches were used
      according to this classification. Near-migrated discs were treated with "half-and
      half" technique, which involved positioning a beveled working sheath across the
      disc space to the epidural space. Far-migrated discs were treated with
      "epiduroscopic" technique, which involved introducing the endoscope into the
      epidural space completely. The mean follow-up period was 14.5 (range 9-20)
      months. According to the Macnab criteria, satisfactory results were as follows:
      91.6% (98/107) in the down-migrated discs; 88.9% (8/9) in the up-migrated discs;
      97.4% (76/78) in the near-migrated discs; and 78.9% (30/38) in the far-migrated
      discs. The mean VAS score decreased from 7.5 +/- 1.7 preoperatively to 2.6 +/-
      1.8 at the final follow-up (P < 0.0001). There were no recurrence and no approach
      related complications during the follow-up period. The proposed classification
      and approaches will provide appropriate surgical guideline of PELD for migrated
      disc herniation. Based on our results, open surgery should be considered for far
      migrated disc herniations.

PMID- 16972068
TI  - Calculated versus measured creatinine clearance for dosing methotrexate in the
      treatment of primary central nervous system lymphoma.
AB  - BACKGROUND: High-dose methotrexate (HDMTX) (>or=3 g/m2), the cornerstone of
      therapy for primary CNS lymphoma (PCNSL), is commonly dosed using a measured 24 h
      creatinine clearance (CrCl) every 2-4 weeks. Because these collections are
      cumbersome and at times unreliable, the use of a calculated CrCl was evaluated as
      a potential alternative. METHODS: A retrospective analysis was performed on data
      from all 287 treatment cycles from the 25 patients with PCNSL who participated in
      a multi-center phase II clinical trial of HDMTX conducted by the New Approaches
      to Brain Tumor Therapy (NABTT) CNS Consortium. RESULTS: The 25 patients had a
      median age of 61 years (range 32-75). Seventeen (68%) were men. The patients
      received a median of 14 (range 2-21) HDMTX treatments. For 256 of 287 treatments
      (89%), data were available to compare the measured and calculated (using the
      Cockcroft-Gault equation) CrCl. The average measured CrCl was 93 ml/min (95% CI,
      89-96 ml/min), and the average calculated CrCl was 107 ml/min (95% CI, 102-112
      ml/min). The Pearson correlation coefficient (r) was 0.49 (P<0.0001) between the
      measured and calculated CrCl. The average MTX dose determined using measured CrCl
      was 14.1 g (95% CI, 13.6-14.5 g), and the average MTX dose determined using
      calculated CrCl was 14.7 g (95% CI, 14.2-15.1 g). MTX doses based on measured and
      calculated CrCl were significantly correlated (r=0.72, P<0.0001). Of the 256
      HDMTX treatments evaluated, 158 (62%) had reliable 48 h serum MTX levels
      documented. Forty-seven levels (30%) were within target range (0.3-1 micromol/l),
      99 levels (62%) were below target range (<0.3 micromol/l), 12 levels (8%) were in
      the range associated with mild toxicity range (>1-3 micromol/l), and no levels
      were in the range associated with severe toxicity (>3 micromol/l). Of these 158
      treatments, the use of a calculated rather than measured CrCl would have yielded
      an identical MTX dose for 48 treatments (30%), a higher MTX dose for 62
      treatments (40%), and a lower MTX dose for 48 treatments (30%). This distribution
      was not significantly different among the subsets of below target, within target
      range, and above target MTX levels (P=0.87). CONCLUSIONS: In this cohort of
      patients with PCNSL, there is significant correlation between the calculated and
      measured CrCl. MTX doses determined using calculated and measured CrCl are not
      significantly different. For these patients, there is no clear association
      between the method of determining CrCl and serum MTX levels. As a result,
      calculated CrCl is a reasonable alternative to measured CrCl in this patient
      population and would avoid the inconvenience and potential inaccuracies
      associated with measured CrCl.

PMID- 16972069
TI  - Paclitaxel induced apoptosis in breast cancer cells requires cell cycle transit
      but not Cdc2 activity.
AB  - PURPOSE: Paclitaxel (PTX) is a widely used chemotherapy agent and may cause cell
      death by apoptosis subsequent to microtubule (MT) disruption. In this paper, we
      have investigated whether cell cycle transit and or Cdc2 (Cdk1) activity is
      required for the apoptosis induced by PTX. METHODS: Cell cycle was analyzed by
      flow cytometry, Cdc2 was assayed bio chemically. Cdc2 activity was decreased by
      siRNA and dominant negative (dn) Cdc2 expression. Cells were arrested by chemical
      or biological inhibitors in a G1 or S phase. Apoptosis was measured by DNA
      fragmentation and examination of nuclei by microscopy. JNK and AKT activations
      were assessed as well. RESULTS: Cell cycle inhibition was highly effective in
      decreasing PTX induced apoptosis. MT morphology was not altered by these
      inhibitors. PTX induced JNK activity or AKT mediated BAD phosphorylation was
      unaffected by cell cycle inhibitors. Abrogation of Cdc 2 activity was without
      effect on PTX induced apoptosis. CONCLUSIONS: While cell cycle transit is
      required for PTX induced apoptosis; Cdc2 activity is not required.

PMID- 16972070
TI  - [Systemic sclerosis].
AB  - Systemic sclerosis (SSc; syn. systemic scleroderma) is a rare autoimmune disorder
      with characteristic cutaneous manifestations. Prevalence in women is fivefold
      higher than in men. The course of the disease is slowly progressive with a
      variable degree of internal organ involvement due to fibrosis and obliteration of
      small vessels. The diffuse form shows more frequent and severe organ
      manifestations compared to the limited form. Increased mortality is particularly
      related to a cardiopulmonary involvement leading to a 5-year survival of around
      75%. Treatment indications are dependent on the severity of the disease. In the
      acute state, immunosuppressive agents are needed in case of significant organ
      involvement. Vasodilative drugs are often used for the symptomatic treatment of
      Raynaud's phenomenon.

PMID- 16972071
TI  - Glucose intolerance in Japanese patients with polycystic ovary syndrome.
AB  - BACKGROUND: Hyperinsulinemia, which is related to obesity, played a pathogenic
      role in polycystic ovary syndrome (PCOS). However, the incidence of obesity in
      Japanese women with PCOS is different from that reported in patients with PCOS in
      Europe and USA. We should determine if insulin resistance occurs in Japanese
      PCOS. The purpose of this study is to assess the presence of insulin resistance
      in Japanese PCOS, while also considering obesity as a factor. METHODS: We divided
      the patients with polycystic ovary (PCO) into three groups based on body mass
      index and levels of gonadotropin. Nine obese PCOS, 34 normal body-weighted PCOS
      (luteinizing hormone (LH)/follicle stimulating hormone (FSH) >1.0) and 11 normal
      LH (LH/FSH </= 1.0), normal body-weighted PCO were studied. We compared those
      patients to 16 control subjects with normal ovulation or with hypothalamic
      anovulation. Eleven women in the control were normal body-weighted and five were
      obese. Patients were given an oral glucose tolerance test. Testosterone, plasma
      glucose and serum immunoreactive insulin after oral administration of 75 g
      dextrose were studied. We also compared glucose-intolerance [total plasma glucose
      (SigmaPG) and insulin (SigmaIRI), insulinogenic index (I.I.), fasting plasma
      glucose/immunoreactive insulin (FPG/IRI), homeostasis model assessment of insulin
      resistance (HOMA-R)] and testosterone among these groups. RESULTS: There were no
      differences in SigmaPG, SigmaIRI, I.I., FPG/IRI or HOMA-R between PCOS and
      controls. However, there were significant differences in SigmaPG, SigmaIRI,
      FPG/IRI and HOMA-R between obese and normal body-weighted patients. Similarly,
      there were no differences in SigmaPG, SigmaIRI, I.I., FPG/IRI or HOMA-R between
      PCOS and controls in the normal body-weighted group. However, there were
      significant differences in SigmaPG, SigmaIRI, FPG/IRI and HOMA-R between the
      obese and the normal body-weighted PCOS. There were also significant differences
      in SigmaPG and I.I. between LH-dominant, normal body-weighted PCOS and normal LH
      PCO. CONCLUSION: Japanese PCOS might have insulin-resistance but the factor of
      obesity had a stronger effect on insulin-resistance than did the existence of
      PCOS. The possibility of a different type of glucose-intolerance was suggested in
      the patients with ultrasonographical PCO in whom gonadotropin secretion was
      abnormal.

PMID- 16972072
TI  - Latency of vestibular responses of pursuit neurons in the caudal frontal eye
      fields to whole body rotation.
AB  - The smooth pursuit system and the vestibular system interact to keep the retinal
      target image on the fovea by matching the eye velocity in space to target
      velocity during head and/or whole body movement. The caudal part of the frontal
      eye fields (FEF) in the fundus of the arcuate sulcus contains pursuit-related
      neurons and the majority of them respond to vestibular stimulation induced by
      whole body movement. To understand the role of FEF pursuit neurons in the
      interaction of vestibular and pursuit signals, we examined the latency and time
      course of discharge modulation to horizontal whole body rotation during different
      vestibular task conditions in head-stabilized monkeys. Pursuit neurons with
      horizontal preferred directions were selected, and they were classified either as
      gaze-velocity neurons or eye/head-velocity neurons based on the previous
      criteria. Responses of these neurons to whole body step-rotation at 20 degrees/s
      were examined during cancellation of the vestibulo-ocular reflex (VOR), VOR x1,
      and during chair steps in complete darkness without a target (VORd). The majority
      of pursuit neurons tested (approximately 70%) responded during VORd with
      latencies <80 ms. These initial responses were basically similar in the three
      vestibular task conditions. The shortest latency was 20 ms and the modal value
      was 24 ms. These responses were also similar between gaze-velocity neurons and
      eye/head-velocity neurons, indicating that the initial responses (<80 ms) were
      vestibular responses induced by semicircular canal inputs. During VOR
      cancellation and x1, discharge of the two groups of neurons diverged at
      approximately 90 ms following the onset of chair rotation, consistent with the
      latencies associated with smooth pursuit. The shortest latency to the onset of
      target motion during smooth pursuit was 80 ms and the modal value was 95 ms. The
      time course of discharge rate difference of the two groups of neurons between VOR
      cancellation and x1 was predicted by the discharge modulation associated with
      smooth pursuit. These results provide further support for the involvement of the
      caudal FEF in integration of vestibular inputs and pursuit signals.

PMID- 16972073
TI  - Gait asymmetry in patients with Parkinson's disease and elderly fallers: when
      does the bilateral coordination of gait require attention?
AB  - While it is known that certain pathologies may impact on left-right symmetry of
      gait, little is known about the mechanisms that contribute to gait symmetry or
      how high in the hierarchy of the control of gait symmetry is regulated in humans.
      To assess the contribution of cognitive function to gait symmetry, we measured
      gait asymmetry (GA) in three subject groups, patients with Parkinson's disease
      (PD, n = 21), idiopathic elderly fallers (n = 15), and healthy elderly controls
      (n = 11). All subjects walked, under two walking conditions: usual walking and
      dual tasking (cognitive loading) condition. For each subject, the swing time (SW)
      was calculated and averaged across strides for the left and right feet (SWL and
      SWR). GA was defined as: 100 x /ln(SWR/SWL)/. For both the PD patients and the
      elderly fallers GA values were significantly higher during the usual walking
      condition, as compared with the control group (P < 0.01). In addition, for both
      the PD patients and the elderly fallers, GA significantly increased when they
      walked and performed a dual task, compared with the usual walking condition (P <
      0.003). In contrast, dual tasking did not affect the GA of the healthy controls
      (P = 0.518). GA was associated with gait speed and gait variability, but no
      correlations were found between GA and the asymmetry of the classic PD motor
      symptoms. Thus, the results suggest that the ability to generate a steady,
      rhythmic walk with a bilaterally coordinated gait does not rely heavily on mental
      attention and cognitive resources in healthy older adults. In contrast, however,
      when gait becomes impaired and less automatic, GA apparently relies on cognitive
      input and attention.

PMID- 16972074
TI  - Phasic increases in cortical beta activity are associated with alterations in
      sensory processing in the human.
AB  - Oscillatory activity in the beta (beta)-frequency band (13-35 Hz) can be recorded
      over the sensorimotor cortex in humans. It is coherent with electromyographic
      activity (EMG) during tonic contraction, but whether the cortical beta
      oscillations are primarily motor or sensorimotor in function remains unclear. We
      tested the hypothesis that cortical beta-activity is associated with an up
      regulation of sensory inputs that may be relevant to the organization of the
      motor response. We recorded cortical somatosensory potentials (SEPs) elicited by
      electrical stimuli to the median nerve at the wrist triggered by increases of
      electroencephalographic (EEG) beta-activity in the contralateral fronto-central
      EEG and compared these to SEPs presented at random intervals. The involvement of
      motor cortex in the triggering EEG activity was confirmed by a simultaneous
      elevation of cortico-spinal synchrony in the beta-band. The negative cortical
      evoked potential peaking at 20 ms and the positive evoked potential peaking at 30
      ms after median nerve shocks were increased in size when elicited after phasic
      increases in beta-activity. The functional coupling of sensory and motor cortices
      in the beta-band was confirmed in recordings of electrocorticographic activity in
      two patients with chronic pain syndromes, suggesting a means by which beta
      activity may simultaneously influence cortical sensory processing, motor output
      and promote sensory-motor interaction.

PMID- 16972075
TI  - Various conflicts from ventral and dorsal streams are sequentially processed in a
      common system.
AB  - Event-related potentials (ERPs) were recorded in subjects while they were
      matching two sequentially presented color spots. The two spots might be presented
      in the same position of the same color, or different colors (color conflict).
      They might be in different positions of the same color (position conflict), or
      different colors (color and position conjunction conflicts). Subjects matched the
      stimuli in three different sessions according to different attention tasks:
      attending to color, attending to position, or attending to both color and
      position. A negative one-peak brain potential, N270, was elicited in all the
      conflict conditions with amplitude enhanced in the task-relevant conflict. Two
      negative effects, N270 and N400, were recorded when attending to the conjunction
      conflicts concurrently. Visual spatial information is processed through the
      dorsal stream, while the feature information is processed through the ventral
      stream in the brain. The results suggest that all kinds of conflicts might be
      processed in a common system above the level of the two streams, which processes
      the conjunction conflict information from ventral and dorsal stream in series.

PMID- 16972077
TI  - Increased blood spermine levels decrease the cytotoxic activity of lymphokine
      activated killer cells: a novel mechanism of cancer evasion.
AB  - Increased blood polyamine levels, often observed in cancer patients, have
      negative impacts on patient prognosis and are associated with tumor progression.
      The purpose of our study was to examine the effects of polyamines on cellular
      immune function. Peripheral blood mononuclear cells (PBMCs) from healthy
      volunteers were cultured with the human natural polyamines spermine, spermidine,
      or putrescine, and the effects on immune cell function were examined. The
      correlation between post-operative changes in blood polyamine levels and
      lymphokine-activated killer (LAK) activity was also examined in cancer patients.
      Spermine decreased the adhesion of non-stimulated PBMCs to tissue culture plastic
      in a dose- and a time-dependent manner without affecting cell viability or
      activity. This decrease in adhesion capacity was accompanied by a decrease in the
      number of CD11a bright-positive and CD56 bright-positive cells. Upon stimulation
      with interleukin 2 to activate LAK cytotoxicity, PBMCs cultured overnight with
      100 or 500 microM spermine showed decreased cytotoxic activity against Daudi
      cells (91.5 +/- 1.7 and 84.9 +/- 3.0%, respectively (n = 6) compared to PBMC
      cultured without polyamines). In a group of 25 cancer patients, changes in blood
      spermine levels after surgery were negatively correlated with changes in LAK
      cytotoxicity after surgery (r = -0.510, P = 0.008: n = 25). Increased blood
      spermine levels may be an important factor in the suppression of anti-tumor
      immune cell function.

PMID- 16972076
TI  - Opposite impact on 14C-2-deoxyglucose brain metabolism following patterns of high
      and low frequency repetitive transcranial magnetic stimulation in the posterior
      parietal cortex.
AB  - Repetitive transcranial magnetic stimulation (rTMS) appears capable of modulating
      human cortical excitability beyond the duration of the stimulation train.
      However, the basis and extent of this "off-line" modulation remains unknown. In a
      group of anesthetized cats, we applied patterns of real or sham focal rTMS to the
      visuo-parietal cortex (VP) at high (HF) or low (LF) frequency and recorded brain
      glucose uptake during (on-line), immediately after (off-line), or 1 h after
      (late) stimulation. During the on-line period LF and HF rTMS induced a
      significant relative reduction of (14)C-2DG uptake in the stimulated VP cortex
      and tightly linked cortical and subcortical structures (e.g. the superficial
      superior colliculus, the pulvinar, and the LPl nucleus) with respect to homologue
      areas in the unstimulated hemisphere. During the off-line period HF rTMS induced
      a significant relative increase in (14)C-2DG uptake in the targeted VP cortex,
      whereas LF rTMS generated the opposite effect, with only mild network impact.
      Moderate distributed effects were only recorded after LF rTMS in the posterior
      thalamic structures. No long lasting cortical or subcortical effects were
      detected during the late period. Our findings demonstrate opposite modulation of
      rTMS on local and distant effects along a specific network, depending on the
      pattern of stimulation. Such effects are demonstrated in the anesthetized animal,
      ruling out behavioral and non-specific reasons for the differential impact of the
      stimulation. The findings are consistent with previous differential
      electrophysiological and behavioral effects of low and high frequency rTMS
      patterns and provide support to uses of rTMS in neuromodulation.

PMID- 16972078
TI  - The fatty acid amide hydrolase 385 A/A (P129T) variant: haplotype analysis of an
      ancient missense mutation and validation of risk for drug addiction.
AB  - The human fatty acid amide hydrolase (FAAH) missense mutation c.385 C-->A, which
      results in conversion of a conserved proline residue to threonine (P129T), has
      been associated with street drug use and problem drug abuse. Although a link
      between the FAAH P129T variant and human drug abuse has been reported, the extent
      of risk and specific types of substance addiction vulnerability remain to be
      determined. Here, we investigated the relationship of the FAAH P129T variant to a
      number of linked single nucleotide polymorphisms to establish a haplotyping
      system, calculate the estimated age and origin of the FAAH 385 C-->A mutation and
      evaluate its association with clinically significant drug addiction in a case
      control study. The results showed a significant over-representation of the FAAH
      P129T homozygotes in 249 subjects with documented multiple different drug
      addictions compared to drug free individuals of the same ethnic backgrounds (P =
      0.05) using logistic regression analysis controlling for ethnicity. To increase
      the logistic regression analysis power by increasing the sample size, the data
      from our previous study (Sipe et al. in Proc Natl Acad Sci USA 99:8394-8399,
      2002) were pooled with the present cohort which increased the significance to P =
      0.00003. Investigation of the FAAH chromosomal backgrounds of the P129T variant
      in both multiple different drug addicted and control subjects revealed a common
      ancestral haplotype, marked population differences in haplotype genetic diversity
      and an estimated P129T mutation age of 114,425-177,525 years. Collectively, these
      results show that the P129T mutation is the only common mutation in the FAAH gene
      and is significantly associated with addictive traits. Moreover, this mutation
      appears to have arisen early in human evolution and this study validates the
      previous link between the FAAH P129T variant and vulnerability to addiction of
      multiple different drugs.

PMID- 16972079
TI  - Additional evidence of a locus for complex febrile and afebrile seizures on
      chromosome 12q22-23.3.

PMID- 16972080
TI  - Microcephaly and simplified gyral pattern of the brain associated with early
      onset insulin-dependent diabetes mellitus.
AB  - Two families are presented with a child suffering from microcephaly with a
      simplified gyral pattern of the brain (SGP) and early onset insulin dependent
      diabetes mellitus (IDDM). The first patient was diagnosed postmortally with
      Wolcott-Rallison syndrome, after her younger brother developed IDDM, and a
      homozygous mutation in the eukaryotic translation initiation factor 2-alpha
      kinase 3 was found. The younger brother did not undergo magnetic resonance
      imaging (MRI). The patient from the second family has no EIF2AK3 mutation. SGP is
      considered to arise from decreased neuronal proliferation or increased apoptosis
      at an early stage of embryonal development, but insight into the pathways
      involved is minimal. EIF2AK3 is involved in translation initiation. It has been
      proposed that loss of function mutations reduce the ability of the cell to
      respond to endoplasmic reticulum stress, resulting in apoptosis of pancreatic
      Langerhans cells. Our findings suggest that in some cases, early onset IDDM and
      SGP can arise from common mechanisms leading to increased apoptosis.

PMID- 16972081
TI  - Pin1 levels are downregulated during ER stress in human neuroblastoma cells.
AB  - Previously, we showed that pretangle neurons in Alzheimer's disease (AD) brain
      display unfolded protein stress in the endoplasmic reticulum (ER). Others showed
      that the peptidylprolyl isomerase Pin1 protects against tangle formation by
      facilitating tau dephosphorylation, corroborating with the lower expression of
      Pin1 observed in tangle-bearing neurons. In this study, we investigated Pin1
      expression under ER stress conditions. We show that in human, but not mouse
      neuroblastoma cells, Pin1 is downregulated in response to ER stress, in
      accordance with the presence of an ER stress response element in the mouse, but
      not the human Pin1 gene. This study creates a starting point to investigate
      whether modulation of the ER stress response may prevent or delay tau pathology
      in AD.

PMID- 16972082
TI  - Electroretinographic abnormalities in multiple sclerosis: possible role for
      retinal autoantibodies.
AB  - BACKGROUND: Multiple sclerosis (MS) has been associated with inflammation of the
      uveal tract, suggesting an immunological link between the uvea and central
      nervous system (CNS) in this disease. The retina is embryologically derived from
      the CNS, and it is conceivable that retinal antigens may also be recognized by
      the immune system in MS. Electroretinographic abnormalities, as well as retinal
      autoantibodies, have previously been described in MS. We performed this study to
      further explore the possibility of retinal autoimmunity in MS. METHODS: Thirty
      four patients with clinically definite MS and thirty-seven healthy controls were
      recruited. All patients and controls had standard electroretinographic (ERG)
      testing done, as well as a brightflash ERG protocol to isolate rod photoreceptor
      function. Patient and control sera were analyzed for the presence of antiretinal
      antibodies using Western blot techniques. RESULTS: We found statistically
      significant differences between MS patients and controls in four ERG parameters.
      In the MS group, implicit times of the rod-cone b-wave response, cone b-wave
      response, and rod photoreceptor response were increased. The amplitudes of the
      photopic oscillatory potentials were reduced in the MS group. Patients with the
      highest titres of retinal autoantibodies had delayed rod-cone b-wave implicit
      times and diminished photopic oscillatory potential amplitudes. CONCLUSIONS: We
      report ERG evidence of retinal dysfunction in patients with MS. We also report
      the first use of the brightflash ERG protocol in MS, which demonstrated rod
      photoreceptor dysfunction. Patients with the highest antiretinal antibody titres
      had abnormal ERG recordings. Retinal autoimmunity is a possible explanation for
      these observed ERG abnormalities in MS patients.

PMID- 16972083
TI  - Acute effects of cigarette smoking on pattern electroretinogram.
AB  - In this study, acute effects of cigarette smoking on the pattern
      electroretinogram (PERG) were investigated. First, variability of the PERG was
      studied in a group of young male smokers (26 right eyes of 26 subjects). Then
      PERGs were investigated in a group of habitual smokers (17 right eyes of 17
      subjects) in separate real smoking and sham smoking sessions. On each session
      PERGs were recorded pre-smoking (PS), immediately after smoking (IAS) and 5 min
      after smoking (5th) conditions. Real smoking significantly increased P50
      amplitudes and decreased N95 latencies. Regarding P50 amplitudes in the real
      smoking sessions, the differences were significant between PS and IAS (PS: 3.3 +/
      0.5 muV, IAS: 3.7 +/- 0.7microV, P = 0.015) and between PS-5th (PS: 3.3 +/-
      0.5microV, 5th: 4.1 +/- 0.9microV, P = 0.039). There was significant difference
      (P = 0.024) between N95 latencies of PS (98.5 +/- 6.9 ms) and IAS (94.7 +/- 5.1
      ms) in the real smoking sessions. No statistically significant difference was
      observed in sham smoking sessions. Our results indicated, for the first time,
      that cigarette smoking may influence PERG amplitude and latency significantly in
      habitual smokers.

PMID- 16972084
TI  - A comparison of pattern and multifocal electroretinography in the evaluation of
      age-related macular degeneration and its treatment with photodynamic therapy.
AB  - This study compares pattern electroretinography (PERG) and multifocal
      electroretinography (mfERG) measures in 13 patients with predominantly classic
      choroidal neovascularisation (CNV) associated with age-related macular
      degeneration (ARMD, 9/13 unilateral, 4/13 bilateral), assesses the usefulness of
      each test in monitoring disease progression, and identifies electrophysiological
      predictors of outcome following treatment with photodynamic therapy (PDT). PERG
      and mfERGs were recorded at presentation, 2 weeks post-treatment, and at 3
      monthly intervals for 2 years. The PERG was detectable in 8/13 patients with
      unilateral disease; the mfERG was detectable in 12/13 patients. P50 and N95
      amplitudes increased in 6/8 patients and mfERG p1 increased in 7/13 patients at 2
      years. PERG amplitudes correlated strongly with mfERG amplitudes in patients with
      unilateral disease. PERG P50 and mfERG p1 amplitude correlated with visual acuity
      at 2 years (R = 0.68, R = 0.82, respectively). The largest PERG P50 and mfERG p1
      amplitude difference between treated and fellow eyes of all the groups on initial
      visit was associated with a poor visual outcome (P50 64% difference; p1 29%
      difference) whereas those with the smallest P50 and p1 amplitude difference was
      associated with improved vision at 2 years (P50 30% difference; p1 21%
      difference). The PERG and mfERG provide an objective measure of central retinal
      function in the progression of ARMD. A detectable PERG on presentation was the
      single best indicator of improved function and visual acuity at 2 years. The
      mfERG demonstrated disease progression from central retina into the paramacular
      regions over 2 years. Patients with poor visual outcomes had the largest inter
      ocular amplitude difference on presentation, suggesting that such patients may
      have a worse prognosis following treatment.

PMID- 16972085
TI  - Full-house nephropathy in a patient with negative serology for lupus.
AB  - A 10-year-old girl presented with a complaint of recurrent abdominal pain.
      Physical examination findings were unremarkable. Laboratory investigations
      revealed BUN of 17 mg/dl and creatinine of 1 mg/dl, and complement levels were
      normal. She had neither hematuria nor proteinuria, and glomerular filtration rate
      was 60.9 ml/min/1.73 m(2). ANA, anti-DNA, p-ANCA and c-ANCA were all negative.
      Renal biopsy revealed findings of class III lupus nephritis in light, "full
      house" nephropathy in immune fluorescent and tubuloreticular inclusions in
      electron microscopic examinations. After 17 months of treatment, her last
      creatinine is 2.5 mg/dl and GFR is 17.9 ml/min/1.73 m(2) and ANA and anti-DNA
      remain still negative. This case presents an example that decreased GFR can be
      the first presenting symptom of full-house nephropathy. Those patients who have
      negative lupus serology and renal biopsy findings of full-house nephropathy and
      tubuloreticular inclusions may behave and should be treated as lupus nephritis.

PMID- 16972086
TI  - Physiologic regulation of central and peripheral T cell tolerance: lessons for
      therapeutic applications.
AB  - Immunologic tolerance is a state of unresponsiveness that is specific for a
      particular antigen. The immune system has an extraordinary potential for making T
      cell and B cell that recognize and neutralize any chemical entity and microbe
      entering the body. Certainly, some of these T cells and B cells recognize self
      components; therefore, cellular mechanisms have evolved to control the activity
      of these self-reactive cells and achieve immunological self-tolerance. The most
      important in vivo biological significance of mechanisms regulating self-tolerance
      is to prevent the immune system from mounting an attack against the host's own
      tissues resulting in autoimmunity. This review summarizes recent developments in
      our understanding of T-helper cell tolerance and discusses how the new findings
      can be exploited to prevent and treat autoimmune diseases, allergy, cancer, and
      chronic infection, or establish donor-specific transplantation tolerance.

PMID- 16972087
TI  - Quantitative real-time RT-PCR data analysis: current concepts and the novel "gene
      expression's CT difference" formula.
AB  - For quantification of gene-specific mRNA, quantitative real-time RT-PCR has
      become one of the most frequently used methods over the last few years. This
      article focuses on the issue of real-time PCR data analysis and its mathematical
      background, offering a general concept for efficient, fast and precise data
      analysis superior to the commonly used comparative CT (DeltaDeltaCT) and the
      standard curve method, as it considers individual amplification efficiencies for
      every PCR. This concept is based on a novel formula for the calculation of
      relative gene expression ratios, termed GED (Gene Expression's CT Difference)
      formula. Prerequisites for this formula, such as real-time PCR kinetics, the
      concept of PCR efficiency and its determination, are discussed. Additionally,
      this article offers some technical considerations and information on statistical
      analysis of real-time PCR data.

PMID- 16972088
TI  - Speciation and structure of ferriprotoporphyrin IX in aqueous solution:
      spectroscopic and diffusion measurements demonstrate dimerization, but not mu-oxo
      dimer formation.
AB  - Changes in epsilon (393) (the Soret band) of aqueous ferriprotoporphyrin IX
      [Fe(III)PPIX] with concentration indicate that it dimerizes, but does not form
      higher aggregates. Diffusion measurements support this observation. The diffusion
      coefficient of aqueous Fe(III)PPIX is half that of the hydrated monomeric dicyano
      complex. Much of the apparent instability of aqueous Fe(III)PPIX solutions could
      be attributed to adsorption onto glass and plastic surfaces. However, epsilon
      (347) was found to be independent of the aggregation state of the porphyrin and
      was used to correct for the effects of adsorption. The UV-vis spectrum of the
      aqueous dimer is not consistent with that expected for a mu-oxo dimer and the
      (1)H NMR spectrum is characteristic of five-coordinate, high-spin Fe(III)PPIX.
      Magnetic susceptibility measurements using the Evans method showed that there is
      no antiferromagnetic coupling in the dimer. By contrast, when the mu-oxo dimer is
      induced in 10% aqueous pyridine, characteristic UV-vis and (1)H NMR spectra of
      this species are observed and the magnetic moment is consistent with strong
      antiferromagnetic coupling. We propose a model in which the spontaneously formed
      aqueous Fe(III)PPIX dimer involves noncovalent interaction of the unligated faces
      of two five-coordinate H(2)O/HO-Fe(III)PPIX molecules, with the axial H(2)O/OH(-)
      ligands directed outwards. This arrangement is consistent with the crystal
      structures of related five-coordinate iron(III) porphyrins and accounts for the
      observed pH dependence of the dimerization constant and the spectra of the
      monomer and dimer. Structures for the aqueous dimer are proposed on the basis of
      molecular dynamics/simulated annealing calculations using a force field
      previously developed for modeling metalloporphyrins.

PMID- 16972089
TI  - [Intravesical treatment of overactive bladder syndrome].
AB  - Overactive bladder and urgency incontinence are common conditions generally
      treated with oral anticholinergic medication. Despite the development of new
      antimuscarinic substances, many patients are refractory to or cannot tolerate the
      oral therapy due to severe side effects. Intravesical instillation therapy can
      provide an alternative method to manage detrusor overactivity. Intravesical
      instillation of anticholinergics such as oxybutynin and trospium chloride can
      achieve cholinergic blockade without producing systemic side effects. Botulinum
      toxin type A injections into the detrusor have been shown to increase bladder
      capacity and to decrease detrusor overactivity for 6 or more months. Intravesical
      local anesthetics such as lidocaine and bupivacaine block the conduction of
      unmyelinated C fibers which results in an increase of functional bladder
      capacity. Intravesical capsaicin and resiniferatoxin also affect the afferent C
      fiber innervation of the bladder, leading to a decrease in detrusor overactivity
      and also an increased bladder capacity. The use of intravesical anticholinergics
      and of local anesthetic medications, both known for their short-term efficacy, is
      limited due to the necessity of daily intermittent catheterization. In
      conclusion, intravesical therapies can provide an alternative treatment for the
      management of overactive bladder.

PMID- 16972090
TI  - Deletion of RNQ1 gene reveals novel functional relationship between divergently
      transcribed Bik1p/CLIP-170 and Sfi1p in spindle pole body separation.
AB  - Spindle pole body (SPB; the microtubule organizing center in yeast) duplication
      is essential to form a bipolar spindle. The duplicated SPBs must then separate
      and migrate to opposite sides of the nucleus. We identified a novel functional
      relationship in SPB separation between the microtubule stabilizing protein
      Bik1p/CLIP-170 and the SPB half-bridge protein Sfi1p. A genetic interaction
      between BIK1 and SFI1 was discovered in a synthetic lethal screen using a strain
      deficient in the prion protein gene RNQ1. RNQ1 deletion reduced expression from
      the divergently transcribed BIK1, allowing us to identify genetic interactors
      with bik1. The sfi1-1 bik1 synthetic lethality was suppressed by over-expression
      of CIK1, KAR1, and PPH21. Genetic analysis indicated that the sfi1-1 bik1
      synthetic lethality was unlikely related to the function of Bik1p in the dynein
      pathway or to defects in spindle position. Furthermore, a sfi1-1 Deltakip2 mutant
      was viable, suggesting that the Bik1p pool at the cytoplasmic microtubule plus
      ends may not be required in sfi1-1. Microscopic examination indicated the sfi1-1
      mutant was delayed in SPB duplication, SPB separation, or spindle elongation and
      the sfi-1 Deltabik1 double mutant arrested with duplicated but unseparated SPBs.
      These results suggest that Bik1p has a previously uncharacterized function in the
      separation of duplicated SPBs.

PMID- 16972091
TI  - Ectopic expression of ThCYP1, a stress-responsive cyclophilin gene from
      Thellungiella halophila, confers salt tolerance in fission yeast and tobacco
      cells.
AB  - The halophyte Thellungiella halophila (salt cress) is an ideal model system for
      studying the molecular mechanisms of salinity tolerance in plants. Herein, we
      report the identification of a stress-responsive cyclophilin gene (ThCYP1) from
      T. halophila, using fission yeast as a functional system. The expression of
      ThCYP1 is highly inducible by salt, abscisic acid (ABA), H(2)O(2) and heat shock.
      Ectopic overexpression of the ThCYP1 gene enhance the salt tolerance capacity of
      fission yeast and tobacco (Nicotiana tabacum L.) cv. Bright Yellow 2 (BY-2) cells
      significantly. ThCYP1 is expressed constitutively in roots, stems, leaves and
      flowers, with higher expression occurring in the roots and flowers. The ThCYP1
      proteins are distributed widely within the cell, but are enriched significantly
      in the nucleus. The present results suggest that ThCYP1 may participate in
      response to stresses in the salt cress, perhaps by regulating appropriate folding
      of certain stress-related proteins, or in the signal transduction processes.

PMID- 16972092
TI  - Genetic transformation of Gentiana macrophylla with Agrobacterium rhizogenes:
      growth and production of secoiridoid glucoside gentiopicroside in transformed
      hairy root cultures.
AB  - Hairy root cultures of Gentiana macrophylla were established by infecting the
      different explants four Agrobacterium rhizogenes strains namely A(4)GUS, R1000,
      LBA 9402 and ATCC11325, and hairy root lines were established with A. rhizogenes
      strain R1000 in 1/2 MS + B(5) medium. Initially, 42 independent hairy root clones
      were maintained and seven clones belongs to different category were evaluated for
      growth, morphology, integration and expression of Ri T-DNA genes, and alkaloid
      contents in dry root samples. On the basis of total root elongation, lateral root
      density and biomass accumulation on solid media, hairy root clones were separated
      into three categories. PCR and Southern hybridization analysis revealed both left
      and right T-DNA integration in the root clones and RT-PCR analysis confirmed the
      expression of hairy root inducible gene. GUS assay was also performed to confirm
      the integration of left T-DNA. The accumulation of considerable amounts of the
      root-specific secoiridoid glucosides gentiopicroside was observed in GM1 (T +/L
      and T +/R) and the GM2 (T +/L and T -/R DNA) type clones in considerably higher
      amount whether as two T -/L but T +/R callus-type clones (GM3) accumulated much
      less or only very negligible amounts of gentiopicroside. Out of four media
      composition the 1/2 MS + B(5) vitamin media was found most suitable. We found
      that initial establishment of root cultures largely depends on root:media ratio.
      Maximum growth rate was recorded in 1:50 root:media ratio. The maximum biomass in
      terms of fresh weight (33-fold) was achieved in 1/2 MS + B(5) media composition
      after 35 days in comparison to sixfold increase in control. The biomass increase
      was most abundant maximum from 15 to 30 days. Influence of A. rhizogenes strains
      and Ri plasmid of hairy root induction, the possible role of the T(L)-DNA and
      T(R)-DNA genes on growth pattern of hairy root, initial root inoculum:media ratio
      and effect of media composition is discussed.

PMID- 16972093
TI  - Occurrence of iridoid glycosides in in vitro cultures and intact plants of
      Scrophularia nodosa L.
AB  - Shoot, root, and callus cultures of Scrophularia nodosa L. (Scrophulariaceae)
      were established and cultivated in vitro. Iridoid glycosides, such as
      harpagoside, aucubin, and catalpol were identified by LC-ESI-MS and their
      contents determined by HPLC. For comparison intact plants of S. nodosa were
      analysed. In shoot cultures slightly lower amounts of detectable iridoid
      glycosides (4.36% dry weight) were determined than in the field grown plants
      (4.88%). Concentration of harpagoside was highest in leaves of field plants
      (1.05%) and in flowers of in vitro plantlets (1.10%). For aucubin the highest
      amount was found in the leaves of in vitro plantlets (1.67%) whereas the levels
      of aucubin in the leaves of field plants were remarkably lower. Catalpol was
      produced as a trace compound in intact plants and shoot cultures. Callus and root
      cultures were apparently not able to synthesise iridoid glycosides.

PMID- 16972094
TI  - Induction and cryopreservation of embryogenic cultures from nucelli and immature
      cotyledon cuts of mango (Mangifera indica L. var Zihua).
AB  - In this paper, we described the direct somatic embryogenesis from both immature
      cotyledon cuts and nucelli in the same mango cultivar (Mangifera indica L. var
      Zihua), studied the effect of growth conditions of embryogenic cultures (EMs) on
      cryopreservation and compared the cryopreservation response of EMs induced from
      these two different explants. Histological studies demonstrated that EMs derived
      from nucelli could be induced directly from epidermal cells of both sides of
      nucelli, whereas EMs derived from cotyledon cuts were induced only from epidermal
      cells of the adaxial side of the cotyledons. EMs from either nucelli or cotyledon
      cuts could be maintained in liquid medium or on solid medium and cryopreserved
      using a vitrification procedure. Success of cryopreservation of EMs depended on
      the dehydration treatment and the defined growth conditions during culture but
      not on their origins. When EMs were sampled during their exponential growth phase
      in liquid medium and dehydrated with PVS(3) solution for 5 min, survival of the
      EMs induced from cotyledon cuts and nucelli reached 77.7 and 80%, respectively,
      after cryopreservation in liquid nitrogen for 24 h. Furthermore, when dehydrated
      with PVS(3) solution for 30 min, all EMs induced from cotyledon cuts and 96.7% of
      EMs induced from nucelli could survive after cryopreservation. Cryopreservation
      did not affect the plant regeneration potential of EMs through somatic
      embryogenesis. The protocols of somatic embryogenesis and cryopreservation of
      mango EMs established in this study may offer potential ways to improve mango
      germplasm conservation and genetic improvement.

PMID- 16972095
TI  - 2,4,5-Trichlorophenoxyacetic acid promotes somatic embryogenesis in the rose
      cultivar "Livin' Easy" (Rosa sp.).
AB  - Somatic embryogenesis (SE) offers vast potential for the clonal propagation of
      high-value roses. However, some recalcitrant cultivars unresponsive to commonly
      employed SE-inducing agents and low induction rates currently hinder the
      commercialization of SE technology in rose. Rose SE technology requires
      improvement before it can be implemented as a production system on a commercial
      scale. In the present work, we assessed 2,4,5-trichlorophenoxyacetic acid (2,4,5
      T), a synthetic auxin not previously tested in rose, for its effectiveness to
      induce SE in the rose cultivar "Livin' Easy" (Rosa sp.). We ran a parallel
      comparison to the commonly used 2,4-dichlorophenoxyacetic acid (2,4-D). We tested
      each auxin with two different basal media: Murashige and Skoog (MS) basal medium
      and woody plant medium (WPM). MS medium resulted in somatic embryo production,
      whereas WPM did not. 2,4,5-T induced SE over a greater concentration range than
      2,4-D's and resulted in significantly greater embryo yields. 2,4,5-T at a
      concentration of 10 or 25 microM was better for embrygenic tissue initiation than
      2,4,5-T at 5 microM. Further embryo development occurred when the tissue was
      transferred to plant growth regulator (PGR) free medium or media with 40% the
      original auxin concentration. However, the PGR-free medium resulted in a high
      percentage of abnormal embryos (32.31%) compared to the media containing auxins.
      Upon transfer to germination medium, somatic embryos successfully converted into
      plantlets at rates ranging from 33.3 to 95.2%, depending on treatment. Survival
      rates 3 months ex vitro averaged 14.0 and 55.6% for 2,4-D- and 2,4,5-T-derived
      plantlets, respectively. Recurrent SE was observed in 60.2% of the plantlets
      growing on germination medium. This study is the first report of SE in the
      commercially valuable rose cultivar 'Livin' Easy' (Rosa sp.) and a suitable
      methodology was developed for SE of this rose cultivar.

PMID- 16972096
TI  - Over-expression of a flower-specific transcription factor gene AtMYB24 causes
      aberrant anther development.
AB  - In plants, MYB transcription factors play important roles in many developmental
      processes and various defense responses. AtMYB24, as a member of R2R3-MYB gene
      family in Arabidopsis, was found mainly expressed in flowers, especially in
      microspores and ovules using Northern blots and in situ hybridization. It was
      further found that the expression of AtMYB24 was tightly regulated during anther
      development. Over-expression of AtMYB24 in transgenic plants resulted in
      pleiotropic phenotypes, including dwarfism and flower development defects, in
      particular, producing abnormal pollen grains and non-dehiscence anthers. Further
      analysis showed that the anther development of the AtMYB24-ox lines was retarded
      starting from the anther developmental stages 10-11. At stages 12 and 13, the
      septum and stomium cells of anthers would not break, and fewer or no fibrous
      bands were found in the endothecium and connective cells in the AtMYB24-ox
      plants. Similar aberrant anther phenotype was also observed in the AtMYB24-GR-ox
      lines treated with dexamethasone (DEX). Quantitative real-time PCR showed
      expression of genes involved in phenylpropanoid biosynthetic pathway, such as CHS
      and DFR, and AtGTP2 were altered in AtMYB24-ox lines. These results suggest an
      important role of AtMYB24 in the normal development of anthers in Arabidopsis.

PMID- 16972097
TI  - In vitro culture of tobacco callus on medium containing peptone and phytate leads
      to growth improvement and higher genetic stability.
AB  - Growth and genetic stability of Nicotiana tabacum L. callus were strongly
      improved by replacing the inorganic nitrogen and phosphorus of the Murashige and
      Skoog's medium by a soybean peptone and phytate, respectively. Cell proliferation
      after subcultivation on the modified medium was highly stimulated as evidenced by
      a strong biomass increase; this improvement was mainly due to the organic N
      source. In addition, while calluses grown under standard conditions displayed
      various cell sizes and DNA contents, subcultivation on the modified medium led to
      homogeneous cell size distribution and stable 4C-8C DNA contents through several
      subcultures. This improved genetic stability was due to replacement of inorganic
      P by phytate, provided the presence of peptone. Such new media composition could
      be useful for slow-growing cell suspensions or calluses.

PMID- 16972098
TI  - Agrobacterium-mediated genetic transformation of tea leaf explants: effects of
      counteracting bactericidity of leaf polyphenols without loss of bacterial
      virulence.
AB  - Tea is one of the major crops in Asia and Africa, and its improvement by genetic
      modification is important for economy of many tea-producing regions. Although
      somatic embryos derived from cotyledon explants have been transformed with
      Agrobacterium, the leaves of several commercially important tea cultivars have
      remained recalcitrant to transformation, largely due to bactericidal effect of
      polyphenols that are exuded by tea leaves in vitro. Moreover, the commonly used
      polyphenol adsorbents and antioxidants cannot overcome this problem. Leaf
      explants, however, are more desirable than cotyledon-derived somatic embryos,
      especially when it is necessary to further improve a selected elite and also
      retain its superior traits. Thus, we developed a procedure for Agrobacterium
      mediated genetic transformation of tea leaf explants which is based on the
      presence of L-glutamine in the co-cultivation medium. We then showed that the
      transformation process is facilitated via a protective action of L-glutamine
      against bactericidal effects of leaf polyphenols without affecting the bacterial
      virulence (vir) gene expression.

PMID- 16972099
TI  - An elastic rod model for anguilliform swimming.
AB  - We develop a model for anguilliform (eel-like) swimming as an elastic rod
      actuated via time-dependent intrinsic curvature and subject to hydrodynamic drag
      forces, the latter as proposed by Taylor (in Proc Roy Proc Lond A 214:158-183,
      1952). We employ a eometrically exact theory and discretize the resulting
      nonlinear partial differential evolution both to perform numerical simulations,
      and to compare with previous models consisting of chains of rigid links or masses
      connected by springs, dampers, and prescribed force generators representing
      muscles. We show that muscle activations driven by motoneuronal spike trains via
      calcium dynamics produce intrinsic curvatures corresponding to near-sinusoidal
      body shapes in longitudinally-uniform rods, but that passive elasticity causes
      Taylor's assumption of prescribed shape to fail, leading to time-periodic motions
      and lower speeds than those predicted Taylor (in Proc Roy Proc Lond A 214:158
      183, 1952). We investigate the effects of bending stiffness, body geometry, and
      activation patterns on swimming speed, turning behavior, and acceleration to
      steady swimming. We show that laterally-uniform activation yields stable straight
      swimming and laterally differential activation levels lead to stable turns, and
      we argue that tapered bodies with reduced caudal (tail-end) activation (to
      produce uniform intrinsic curvature) swim faster than ones with uniform
      activation.

PMID- 16972100
TI  - fMRI predictors of treatment outcome in pediatric anxiety disorders.
AB  - INTRODUCTION: A growing number of studies have found evidence that anxiety and
      depressive disorders are associated with atypical amygdala hyperactivation, which
      decreases with effective treatment. Interest has emerged in this phenomenon as a
      possible biological marker for individuals who are likely to benefit from
      tailored treatment approaches. OBJECTIVE: The present study was designed to
      examine relationships between pretreatment amygdala activity and treatment
      response in a sample of anxious children and adolescents. MATERIALS AND METHODS:
      Participants, who were diagnosed predominantly with generalized anxiety disorder
      (GAD), underwent functional magnetic resonance imaging (fMRI) scanning before
      treatment with fluoxetine or cognitive behavioral therapy (CBT). RESULTS: Results
      indicated significant negative associations between degree of left amygdala
      activation and measures of posttreatment symptom improvement in the group, as a
      whole. DISCUSSION: Taken together with research on associations between adult
      amygdala activation and treatment response, these findings suggest that patients
      whose pretreatment amygdala activity is the strongest may be particularly likely
      to respond well to such widely used treatments as selective serotonin reuptake
      inhibitor (SSRI) medications and CBT.

PMID- 16972101
TI  - Chlordiazepoxide and dizocilpine, but not morphine, selectively impair
      acquisition under a novel repeated-acquisition and performance task in rats.
AB  - RATIONALE: Some classes of drugs can selectively affect learning (i.e.,
      acquisition of behavior) at doses that do not affect performance (i.e.,
      previously learned behavior). Some drugs (e.g., benzodiazepines) show selective
      effects on acquisition across a wide variety of tasks. Other drugs [e.g., N
      methyl-D-aspartate (NMDA) antagonists and opiate agonists], however, show
      selective effects under some tasks, but not others. OBJECTIVES: The purpose of
      this study was to examine the effects of the NMDA-antagonist dizocilpine (0.01
      0.3 mg/kg), the opiate-agonist morphine (1.0-17.0 mg/kg), and the benzodiazepine
      chlordiazepoxide (3.0-30.0 mg/kg) in rats under a novel repeated-acquisition and
      performance task. METHODS: Nose pokes to a correct location within a 2x3 stimulus
      array on a computer touch screen were reinforced with food. In the acquisition
      component, the correct location changed across sessions but remained constant
      within sessions; in the performance component, the correct location was constant
      both across and within sessions. RESULTS: Both chlordiazepoxide and dizocilpine
      selectively impaired accuracy in the acquisition component at doses that did not
      affect accuracy in the performance component or overall response speed. Morphine,
      however, did not affect acquisition without affecting performance or response
      speed. CONCLUSIONS: These results with rats resembled those previously obtained
      for response-sequence learning in primates, rather than those previously reported
      for spatial learning in rats. Therefore, previous discrepancies in results for
      NMDA antagonists and opiate agonists across tasks probably were not a function of
      the species studied, but, rather, they more likely were a function of unique
      variables controlling acquisition within each task.

PMID- 16972102
TI  - The impact of moderate daily alcohol consumption on aggression and the formation
      of dominance hierarchies in rats.
AB  - RATIONALE AND OBJECTIVE: Group-housed male rats form social hierarchies, and
      under these conditions, it has been reported that subordinate (SUB) rats consume
      more alcohol than dominant (DOM) rats. We tested the hypothesis that a history of
      drinking alcohol would cause SUB rats to consume even greater amounts of alcohol.
      METHODS: Male Long-Evans rats were trained to drink 10% alcohol or a
      sucrose/quinine solution equal in calories for 1 h/day using a sucrose-fading
      procedure. Subsequently, rats were housed in colonies (four males, two females)
      in a visible burrow system (VBS) for 14 days. Individual control male rats were
      housed in a tub cage with one female. Rats were removed from the VBS (or control
      environment) daily and given 1 h to drink alcohol or sucrose/quinine. RESULTS:
      Colonies given daily access to sucrose/quinine formed clear DOM/SUB relationships
      in all measured parameters. Alcohol-drinking colonies failed to establish a
      dominance hierarchy and displayed little aggression, with an average of 14.6 +/-
      6.1 offensive attacks compared with 58.5 +/- 12.3 attacks carried out by DOM
      sucrose/quinine rats. During VBS housing, alcohol and sucrose/quinine intake
      decreased independent of housing environment or social status. CONCLUSIONS:
      Contrary to prior reports of the effect of alcohol on aggressive behavior,
      moderate daily alcohol intake before and during VBS housing reduced aggression
      and precluded the formation of a dominance hierarchy in rats.

PMID- 16972103
TI  - Individual differences in the propensity to approach signals vs goals promote
      different adaptations in the dopamine system of rats.
AB  - RATIONALE: The way an individual responds to cues associated with rewards may be
      a key determinant of vulnerability to compulsive behavioral disorders.
      OBJECTIVES: We studied individual differences in Pavlovian conditioned approach
      behavior and examined the expression of neurobiological markers associated with
      the dopaminergic system, the same neural system implicated in incentive
      motivational processes. METHODS: Pavlovian autoshaping procedures consisted of
      the brief presentation of an illuminated retractable lever (conditioned stimulus)
      followed by the response-independent delivery of a food pellet (unconditioned
      stimulus), which lead to a Pavlovian conditioned response. In situ hybridization
      was performed on brains obtained either following the first or last (fifth) day
      of training. RESULTS: Two phenotypes emerged. Sign-trackers (ST) exhibited
      behavior that seemed to be largely controlled by the cue that signaled impending
      reward delivery; whereas goal-trackers (GT) preferentially approached the
      location where the reward was delivered. Following a single training session, ST
      showed greater expression of dopamine D1 receptor mRNA relative to GT. After 5
      days of training, GT exhibited greater expression levels of tyrosine hydroxylase,
      dopamine transporter, and dopamine D2 receptor mRNA relative to ST. CONCLUSIONS:
      These findings suggest that the development of approach behavior towards signals
      vs goal leads to distinct adaptations in the dopamine system. The sign-tracker vs
      goal-tracker phenotype may prove to be a valuable animal model to investigate
      individual differences in the way incentive salience is attributed to
      environmental stimuli, which may contribute to the development of addiction and
      other compulsive behavioral disorders.

PMID- 16972104
TI  - Involvement of dopamine D1 and D2 receptors in the nucleus accumbens core and
      shell in inhibitory response control.
AB  - RATIONALE: Impaired inhibitory control over behavior is a key feature in various
      psychiatric disorders, and recent studies indicated an important role for
      dopamine D(1) and D(2) receptors and the nucleus accumbens (Acb) in this respect.
      OBJECTIVE: The present experiments were designed to study the role of dopamine
      D(1) and D(2) receptors in the Acb in inhibitory response control. METHODS: Rats
      were trained in a five-choice serial reaction time task and received bilateral
      infusions into the Acb core or shell of either SCH 23390 or eticlopride
      (representing selective dopamine D(1) and D(2) receptor antagonists,
      respectively). Subsequently, the effects of systemic amphetamine on inhibitory
      response control were examined. RESULTS: Eticlopride into either the Acb core or
      shell did not affect premature responding, a measure for inhibitory response
      control, but increased reaction time and errors of omission. In contrast, SCH
      23390 into both regions reduced premature responding, slightly improved
      attentional performance in the core and increased errors of omission in the
      shell. Amphetamine robustly increased premature responding which was dose
      dependently blocked by eticlopride in the Acb core and attenuated by eticlopride
      in the shell. In addition, amphetamine slightly decreased accuracy and reaction
      time, and these effects were inhibited by eticlopride in both regions. SCH 23390
      infusion into the Acb core or shell did not alter amphetamine's effects.
      CONCLUSION: Our data provide evidence for the involvement of dopamine D(1) and
      D(2) receptors in the Acb core and shell in inhibitory response control and
      attentional performance.

PMID- 16972105
TI  - Depot naltrexone: antagonism of the reinforcing, subjective, and physiological
      effects of heroin.
AB  - RATIONALE: Naltrexone is an opioid antagonist that is currently approved as a
      treatment for opioid and alcohol dependence. Although it is highly effective in
      completely antagonizing the effects of opioids, medication noncompliance is a
      difficult obstacle to treatment. Therefore, a sustained-release form of
      naltrexone may improve treatment outcome. OBJECTIVE: The present study was
      designed to evaluate the time course, safety, and effectiveness of a depot
      formulation of naltrexone (Depotrex). MATERIALS AND METHODS: Five heroin
      dependent individuals participated in an 8-week inpatient study. After a 1-week
      detoxification period, the effects of a range of heroin doses (0, 6.25, 12.5, and
      25 mg, i.v.) were examined. Participants then received 384 mg naltrexone base.
      The effects of heroin were again evaluated for the next 6 weeks. One dose of
      heroin was tested per day and the entire dose range was tested each week. Doses
      were administered in non-systematic order. During a morning sample session,
      participants received a dose of heroin and $20 and subjective, performance, and
      physiological effects were measured both before and after drug administration.
      During an afternoon choice session, participants were given the opportunity to
      choose the sampled heroin dose and/or amount of money using a modified
      progressive ratio procedure. RESULTS: Depot naltrexone antagonized both the
      reinforcing and subjective effects of heroin for 4-5 weeks. Subjective ratings of
      withdrawal were reduced after week 2 and throughout the remainder of the study.
      The effects of heroin on mean trough pupil diameter began to emerge by week 5.
      There were no clinically significant effects on respiratory or cardiovascular
      function. CONCLUSIONS: The present results extend our previous findings by
      showing that the reinforcing effects of heroin were reduced for 4-5 weeks after
      administration of 384 mg depot naltrexone.

PMID- 16972106
TI  - Individual differences in drug abuse vulnerability: d-amphetamine and sensation
      seeking status.
AB  - RATIONALE: While the personality dimensions of novelty seeking and sensation
      seeking are associated with drug abuse vulnerability, the mechanisms associated
      with this vulnerability remain obscure. OBJECTIVE: This study examined the
      behavioral effects of d-amphetamine in healthy volunteers scoring in the upper
      and lower quartiles based on age- and gender-adjusted population norms on the
      impulsive Sensation-Seeking Scale (SSS) of the Zuckerman-Kuhlman personality
      questionnaire (ZKPQ). METHOD: Participants completed 7-day outpatient studies
      examining the subjective, performance, and cardiovascular effects of d
      amphetamine (0, 7.5, and 15 mg/70 kg, p.o.) under double-blind conditions
      according to a randomized block design. Performance tasks included behavioral
      measures of impulsivity, including attention, inhibition, and risk-taking
      behavior. RESULTS: No differences in baseline performance or d-amphetamine
      effects on measures of attention, inhibition, and risk-taking behavior were
      observed. High impulsive sensation seekers reported greater increases on several
      subjective report measures associated with drug abuse potential, including visual
      analog scales feel drug, like drug, and high. CONCLUSIONS: Healthy adults scoring
      in the top quartile on the population of the impulsive SSS of the ZKPQ may be
      vulnerable to the abuse potential of d-amphetamine.

PMID- 16972107
TI  - Measuring the ability to stay awake: role of motivation.

PMID- 16972108
TI  - Arthroscopic loose-body removal in posterior compartment of the knee joint: a
      technical note.
AB  - The arthroscopic removal of loose bodies in the knee joints is a relatively
      common procedure. Quite often intra-articular loose bodies tend to localize at
      the posterior compartment due to gravity effect. However, it is often technically
      demanding to find and remove loose bodies located at the posterior compartment of
      the knee joint arthroscopically. We present the technical aspects of arthroscopic
      removal of the loose bodies located in the posterior compartment of the knee
      joint. Loose bodies at posterior compartment were subdivided into six regions in
      posterior knee compartment with preoperative MRI and arthroscopic findings. Each
      section needs slight different application of arthroscopic techniques for
      removal. We retrospectively studied 52 knees in 50 patients who underwent
      arthroscopic loose-body removal in posterior compartment, in 28 knees, additional
      posterior trans-septal portal was needed for removal of loose bodies. With the
      help of trans-septal portal, we have successfully removed the loose bodies even
      from the most difficult locations in posterior compartment.

PMID- 16972109
TI  - Clinical disability in posterior cruciate ligament deficient patients does not
      relate to knee laxity, but relates to dynamic knee function during stair
      descending.
AB  - We investigated the factors which influence clinical subjective symptoms during
      activities in Posterior cruciate ligament (PCL) deficient patients by evaluating
      knee laxity, muscle strength and knee mechanics during level walking, stair
      ascent and descent. Twenty-two subjects with isolated PCL deficient knees and 20
      healthy volunteers were involved. The PCL deficient patients were divided into
      two subgroups based on previous history of experiencing giving-way during stair
      descent; a giving-way group (10 subjects) and a nongiving-way group (12
      subjects). Giving-way during activities of daily living is a key symptom in
      isolated PCL deficient patients. No statistically significant differences in the
      knee laxity, muscle strength and knee mechanics during level walking and were
      observed between the giving-way group and the nongiving-way group. However, we
      found significant differences in the knee mechanics during stair ascent and
      descent between the two groups, and these differences were more remarkable during
      stair descent. Peak values of knee flexion angle, external knee flexion moment
      and posterior knee force during early stance phase were significantly lower in
      the giving-way group than in the nongiving-way group. This study indicated that
      the symptom of giving-way during stair descent was related to knee mechanics
      during stair descent, unlike other quantitative evaluations such as KT-2000 or
      Biodex.

PMID- 16972110
TI  - Reconstruction of the anterior cruciate ligament: dynamic strain evaluation of
      the graft.
AB  - The study is focused on the biomechanical aspects of the anterior cruciate
      ligament (ACL) reconstruction procedures with an emphasis on evaluating the
      dynamic strain of materials commonly used for this purpose. Separate and
      multiple, equally tensioned strands of hamstring grafts used for the
      reconstruction of the ACL were biomechanically tested and compared to original
      ACL and bone-patellar tendon-bone (BPTB) grafts, using tissue samples from
      cadavers. The study was focused on measuring such material properties as the
      strength, stiffness, maximum load, and elongation at maximum load of the original
      ACL, BPTB graft, and single tendon hamstring (gracilis and semitendinosus)
      grafts, continued by double strands and finally by four-strand graft (STG)
      evaluation. Fresh-frozen cadaveric knees were used, which had been clamped and
      tensioned equally. The measurement was performed by drop-weight testing, using a
      Laser Doppler Vibrometer as a basic sensor of the dynamic movements of the
      gripping clamps, with parallel correlation by a piezoelectric transducer. The
      grafts for experiments were obtained from 21-paired knees. The measurement was
      performed at room temperature (21 degrees C) after 24 h of thawing at 4 degrees
      C. All the specimens were measured for their response to the dynamic tensile
      load. The maximum strength values were obtained and calculated for the
      appropriate section area of the specimen. The tensioned strands of the original
      ACL showed a maximum average load of 1,246 +/- 243 N in the section area of about
      30 mm(2) (max. stress 41.3 MPa); the strands of BPTB grafts showed values of
      3,855 +/- 550 N in the section area of 80 mm(2) (max. stress 40.6 MPa); the
      gracilis tendons showed 925 +/- 127 N in the section area of 10 mm(2) (max.
      stress 95.1 MPa) and the semitendinosuss yielded a result of 2,050 +/- 159 N in
      the area of 20 mm(2) (max. stress 88.7 MPa). Of all the materials, the original
      ACL have the lowest strength and stiffness in respect of their biomechanical
      properties. BPTB grafts showed a slightly higher value of maximum stress, while
      both the gracilis and semitendinosus tendons showed double the value of maximum
      load per section area-tensile stress. Two- and four- combined hamstring strands
      clamped together and equally tensioned with a drop-weight had the combined
      tensile strength properties of the individual strands within the estimated range
      of measurement errors. No significant changes in maximum loads/stresses were
      observed under impact loading conditions. The results of this study demonstrate
      that equally tensioned four-strand hamstring-tendon grafts have higher initial
      tensile properties than those in other varieties of samples. From a biomechanical
      point of view, they seem to be a reasonable alternative procedure for ACL
      reconstruction.

PMID- 16972112
TI  - Abstracts of ESMRMB 2006, 23rd Annual Scientific Meeting of the European Society
      for Magnetic Resonance in Medicine and Biology. Warsaw, Poland. September 21-23,
      2006.

PMID- 16972111
TI  - Interstitial iodine-125 radiosurgery alone or in combination with microsurgery
      for pediatric patients with eloquently located low-grade glioma: a pilot study.
AB  - PURPOSE: The optimal therapeutic management of children with World Health
      Organization grade I and II gliomas not accessible to complete resection is
      poorly defined. Radical surgical resection is the first-line treatment for large
      hemispheric tumors, whereas interstitial iodine-125 radiosurgery (IRS) might be
      an attractive treatment concept for selected patients with small (tumor diameter
      in the range of 4 cm) and circumscribed tumors in any location of the brain.
      Precise high-dose application, maximal sparing of surrounding normal tissue, and
      the absence of long-term complications have been reported to be the hallmark of
      IRS. Therefore, the therapeutic impact and the risk of IRS alone or in
      combination with microsurgery (in case of larger tumor volumes) were
      prospectively examined. METHODS: Seven boys and four girls were included (mean
      age, 6.8 years; range, 11 months to 16 years). IRS (after stereotactic biopsy)
      was considered to be indicated for circumscribed tumors with a diameter in the
      range of 4 cm (four cases). For larger tumors, a combined
      microsurgical/radiosurgical approach was preferred (seven patients). Temporary
      iodine-125 seeds were used exclusively (tumor dose calculated to the boundary, 54
      Gy; dose rate, 10 cGy/h). Tumor location was hypothalamic/suprasellar in four,
      lobar in three, deep (thalamus and pineal gland) in two, and within the brain
      stem in two children. Treatment effects of IRS were estimated according to the
      MacDonald criteria. RESULTS: A complete response after IRS was seen in four
      patients, and a partial response was seen in seven patients (median follow-up,
      31.5 months). There was no perioperative morbidity after microsurgery and/or IRS,
      and no radiogenic complications occurred during the follow-up period. Five
      patients experienced an improvement in their deficits, and no deterioration in
      neurological/endocrine function was seen in any of the patients at the time of
      last follow-up evaluation. CONCLUSION: IRS alone or in combination with
      microsurgery (in the case of larger tumors) is a safe, effective, and minimally
      invasive treatment strategy for eloquently located pediatric low-grade gliomas
      and deserves further prospective evaluation.

PMID- 16972117
TI  - Does brief, clinically based, intensive multimodal behavior therapy enhance the
      effects of methylphenidate in children with ADHD?
AB  - OBJECTIVE: The additional value of a short-term, clinically based, intensive
      multimodal behavior therapy to optimally titrated methylphenidate in children
      with attention-deficit hyperactivity disorder (ADHD) was investigated. METHOD:
      Fifty children with ADHD (ages 8-12) were randomized to treatment of
      methylphenidate or treatment with methylphenidate combined with 10 weeks of
      multimodal behavior therapy. The multimodal behavior therapy consisted of a child
      and parent behavioral therapy and a teacher behavioral training. Assessments
      included parent, teacher and child ratings of ADHD symptoms, oppositional and
      conduct behavior, social skills, parenting stress, anxiety and self-worth.
      RESULTS: Both treatment conditions yielded significant improvements on all
      outcome domains. No significant differences were found between both treatments.
      CONCLUSIONS: No evidence was found for the additive effect of multimodal behavior
      therapy next to optimally titrated methylphenidate. CLINICAL IMPLICATIONS: This
      study does not support the expectation that optimally dosed stimulant treated
      children with ADHD should routinely receive psychosocial treatment to further
      reduce ADHD- and related symptoms.

PMID- 16972119
TI  - Acute axonal neuropathy and Wernicke's encephalopathy.

PMID- 16972118
TI  - No hyperactive-impulsive subtype in teacher-rated attention-deficit/hyperactivity
      problems.
AB  - The aim of this study was to investigate which homogeneous groups, according to
      teacher reports of attention-deficit/hyperactivity (ADH) Problems on the
      Teacher's Report Form (TRF), can be identified in a referred sample (n = 4,422;
      age = 6-18 years; mean age = 9.9 years; 66% boys, 34% girls). Latent class
      analysis (LCA) was conducted on ADH Problems. In addition, co-morbidity levels in
      the different ADH Problems groups were compared. LCA yielded three different
      groups of children and adolescents with both Inattention and hyperactivity
      impulsivity, and one group with high scores on Inattention but low scores on
      hyperactivity-impulsivity. A group of patients with predominantly hyperactivity
      and impulsivity was not found. Individuals in groups with higher levels of ADH
      Problems had significantly higher levels of oppositional defiant (OD) and conduct
      problems, and, although to a lesser extent, significantly higher levels of
      affective and anxiety problems than individuals in groups with lower levels of
      ADH Problems. It may not be useful to discern the hyperactive-impulsive type of
      ADHD.

PMID- 16972120
TI  - Spinocerebellar ataxia type 17 in a patient from an Indian kindred.

PMID- 16972121
TI  - Copper deficiency myelopathy induced by repetitive parenteral zinc
      supplementation during chronic hemodialysis.

PMID- 16972122
TI  - Subcutaneous self-infusions of immunoglobulins as a potential therapeutic regimen
      in immune-mediated neuropathies.

PMID- 16972123
TI  - No association between synapsin III gene promoter polymorphisms and multiple
      sclerosis in German patients.
AB  - We investigated whether the polymorphisms rs133946 and rs133945 in the promoter
      region of the synapsin III (SYN3) gene are associated with multiple sclerosis in
      German patients. Association of the SYN3 variations and haplotypes with MS is not
      evident in German MS patients - in contrast to a MS cohort from Italy, as
      reported previously.

PMID- 16972124
TI  - Evaluation of the anti-terminator Q933 gene as a marker for Escherichia coli
      O157:H7 with high Shiga toxin production.
AB  - The anti-terminator Q933 gene of the bacteriophage 933W was evaluated as a marker
      for Escherichia coli O157:H7 strains with high Shiga toxin production. In total,
      262 environmental strains of E. coli O157:H7 isolated from feces of beef cattle
      and the digestive tract of houseflies were screened for the Q933 and Q21 (anti
      terminator Q21 of bacteriophage 21) genes by polymerase chain reaction. Nine
      (3.4%) isolates tested positive for Q933 alone, 161 (61.5%) were positive for the
      Q21 gene alone, and 92 (35.1%) isolates carried both Q alleles. Results from the
      enzyme-linked immunosorbent assay show that the isolates with Q933 alone produced
      significantly more Shiga toxin than the remaining isolates. The difference was
      even greater after the induction of the toxin production by a short exposure of
      cells to ultraviolet light. These data suggest that Q933 is a promising indicator
      for environmental E. coli O157:H7 with high production of Shiga toxins and,
      therefore, for potentially clinically relevant strains.

PMID- 16972125
TI  - Adenosine diphosphate ribosylation of dinitrogenase reductase and adenylylation
      of glutamine synthetase control ammonia excretion in ethylenediamine-resistant
      mutants of Azospirillum brasilense Sp7.
AB  - Azospirillum brasilense is a nitrogen-fixing, root-colonizing bacterium that
      brings about plant-growth-promoting effects mainly because of its ability to
      produce phytohormones. Ethylenediamine (EDA)-resistant mutants of A. brasilense
      were isolated and screened for their higher ability to decrease acetylene and
      release ammonia in the medium. One of the mutants showed considerably higher
      levels of acetylene decrease and ammonia excretion. Nitrogenase activity of this
      mutant was relatively resistant to inhibition by NH(4)Cl. Adenosine triphosphate
      ribosylation of dinitrogenase reductase in the mutant did not increase even in
      presence of 10 mM NH(4)Cl. Although the mutant showed decreased glutamine
      synthetase (GS) activity, neither the levels of GS synthesized by the mutant nor
      the NH (4) (+) -binding site in the GS differed from those of the parent. The
      main reason for the release of ammonia by the mutant seems to be the fixation of
      higher levels of nitrogen than its GS can assimilate, as well as higher levels of
      adenylylation of GS, which may decrease ammonia assimilation.

PMID- 16972126
TI  - Proteolytic cleavage of a spectrin-related protein by calcium-dependent protease
      in Neurospora crassa.
AB  - To investigate the functional significance of a cytoskeletal spectrin-like
      protein, we studied its localization pattern in Neurospora crassa and sought the
      answer to whether it is a substrate for another apically localized protein, the
      calcium-dependent protease (CDP II). Immunoblots of crude extracts from
      exponentially growing mycelia, separated by one- and two-dimensional sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis using antichicken alpha/beta
      spectrin antibodies, revealed a single band of approximately relative mass (Mr)
      100 kDa with an isoeletric point (pI) in the range of 6.5 to 7.0. Despite
      rigorous efforts, we could not confirm the presence of an Mr 240- to 220-kDa
      spectrin-like protein in N. crassa. The immunofluorescence- and immunogold
      labeling Mr 100-kDa protein showed its predominance along the plasma membrane of
      the conidia during the swelling phase of germination. In contrast, in the germ
      tubes and the growing hyphae, the localization was polarized and concentrated
      mainly in the apical region. The in vitro proteolysis experiments showed that
      indeed this protein is a preferred substrate of CDP II which is, as mentioned
      previously, also localized in the apical regions of the hyphae. These results
      indicate a putative functional relationship between these two proteins (spectrin
      like protein and CDP II) in the dynamics of tip growth.

PMID- 16972127
TI  - Inhibitory effects of some spice and herb extracts against Arcobacter butzleri,
      A. cryaerophilus, and A. skirrowii.
AB  - Seventeen spice and medicinal plant extracts (methanol and chloroform) were
      assayed for their antimicrobial activity against Arcobacter butzleri, A.
      cryaerophilus, and A. skirrowii. In general, all of the tested extracts were
      able, to a different extent, to inhibit the growth of the selected Arcobacter
      species. Cinnamon, bearberry, chamomile, sage and rosemary extracts showed strong
      antimicrobial activity toward arcobacter strains tested. Overall, the methanol
      extracts showed better activity than the chloroform extracts (P < 0.05); however,
      enhanced antibacterial activity of chloroform extracts of cinnamon and rosemary
      has been observed in comparison with their methanol counterparts. The inhibitory
      dose of the most active extracts (the diameter of zone of inhibition > or = 20
      mm) was determined using the disc-diffusion method as well.

PMID- 16972128
TI  - Identification of the critical role of Tyr-194 in the catalytic activity of a
      novel N-acyl-homoserine lactonase from marine Bacillus cereus strain Y2.
AB  - Enzymatic disruption of quorum-sensing (QS) pathways in pathogenic organisms is a
      promising anti-infection therapeutic strategy. AHL-lactonase, a potent tool for
      biocontrol, can hydrolyze QS signal molecule N-acyl-homoserine lactones (AHLs)
      into inactive products, thereby blocking the QS systems. A marine bacterial
      isolate Y2, identified as a Bacillus cereus subsp., was found capable of
      inactivating AHLs. The aiiA gene encoding the AHL-degrading enzyme from bacterial
      strain Y2 was cloned and expressed in Escherichia coli. The 28-kDa recombinant Y2
      AiiA protein was purified and showed strong AHL-degrading activity. Sequence
      comparisons of Y2-aiiA with known AHL-lactonases revealed high identities in the
      deduced amino-acid sequences. Functional determination of a potential catalytic
      residue Tyr-194 of AHL-lactonases was performed by site-directed mutagenesis. As
      judged by AHL-degrading bioassay, substitution of Tyr-194 with Ala resulted in a
      dramatic decrease of activity compared with wild-type (WT) recombinant Y2-AiiA,
      although the expression level of the mutated Y2-AiiA protein was equivalent to
      that of WT Y2-AiiA. These results suggested that the conserved residue Tyr-194 is
      critical for catalytic function of the novel AHL-lactonase.

PMID- 16972129
TI  - Effect of ractopamine HCl supplementation on fecal shedding of Escherichia coli
      O157:H7 and Salmonella in feedlot cattle.
AB  - The effects of the beta-agonist ractopamine, recently approved for use in feedlot
      cattle to improve carcass quality and performance, on fecal shedding Escherichia
      coli O157:H7 and Salmonella in feedlot cattle was examined. In the first study,
      20 feedlot steers and heifers were randomly assigned to receive ractopamine or no
      ractopamine (control) by way of oral bolus for 28 days. Fecal samples were
      collected daily, and shedding of E. coli O157:H7 determined. When examined during
      the entire 28-day experimental period, ractopamine decreased (P = 0.0006) the
      percentage of cattle shedding E. coli O157:H7 (58% vs. 42% for control and
      ractopamine treatments, respectively). A second study was conducted in a
      commercial feedlot facility in the southwestern United States. Eighteen pens of
      cross-bred beef heifers (approximately 100 head/pen and 9 pens/treatment) were
      randomly assigned to receive either 0 (control) or 200 mg ractopamine/head x d(
      1). Fresh fecal samples (30/pen) were collected off the pen floor before
      ractopamine supplementation and again after approximately 28 days of ractopamine
      supplementation (within a few days of slaughter); the samples were cultured for
      E. coli O157:H7 and Salmonella. The percentage of animals shedding E. coli
      O157:H7 was decreased when data were pooled across replicates (P = 0.05) in
      ractopamine-treated cattle compared with controls. The percentage of animals
      shedding Salmonella tended to be higher (P = 0.08) with the ractopamine treatment
      when data were pooled across replicates. Although further research is required to
      confirm these results, the potential food safety implications of this research
      are intriguing.

PMID- 16972130
TI  - A low-cost fermentation medium for thermophilic protease production by
      Streptomyces sp. 594 using feather meal and corn steep liquor.
AB  - Protease production by Streptomyces sp. 594 was obtained after submerged
      fermentation (SF) and solid-state fermentation (SSF) using feather meal (FM) and
      corn steep liquor (CSL) as sole sources of carbon and nitrogen. Enzyme
      productions were 13.4 U ml(-1) in SF and 21.5 U g(-1) in SSF; these values were
      approximately 86% and 39% higher, respectively, than those obtained previously
      when yeast extract was used in place of CSL. The proteases, which belong to the
      serine and metalloproteinase classes, were active at high temperatures (55
      degrees C to 90 degrees C) and over a wide range of pH values (5.0 to 10.0).
      Thus, these thermophilic proteases have shown interesting properties for
      industrial purposes. As far as we are concerned, this is the first contribution
      toward the microbial production of thermophilic proteases by a streptomycete
      using a low-cost medium composed of industrial poultry (FM) and corn processing
      by-products (CSL).

PMID- 16972131
TI  - Antibiotic susceptibility of Helicobacter pylori clinical isolates: comparative
      evaluation of disk-diffusion and E-test methods.
AB  - Antimicrobial susceptibility of 25 Helicobacter pylori strains isolated from
      patients with acid peptic diseases were tested for in vitro sensitivity to
      commonly used antibiotics using disk-diffusion and E-test, methods. All strains
      tested were susceptible to tetracycline by E-test, with the minimum inhibitory
      concentration (MIC) values being <0.125 microg/ml for all strains except for 6
      (<0.023 microg/ml). However 1 strain was resistant by disk-diffusion method. One
      strain was resistant to clarithromycin both by disk diffusion and E-test (MIC <48
      microg/ml), and 1 strain was resistant only by disk diffusion. Only one strain
      was resistant to amoxicillin by disk diffusion and E-test (MIC >256 microg/ml).
      For ciprofloxacin, three strains were resistant by disk diffusion and two by E
      test (MIC <32 microg/ml). Sixteen strains were resistant to metronidazole by disk
      diffusion and E-test (MIC >or= 8 microg/ml), and 1 was resistant only by E-test
      (MIC <48 microg/ml). Overall, 64% of the strains were resistant to metronidazole.
      The MIC for metronidazole was also tested by agar-dilution method, and
      metronidazole resistant strains had an, MIC >8 microg/ml. The disk-diffusion
      method showed excellent correlation with E-test results; there was 100% agreement
      for amoxicillin a other antibiotics showed 90% to 95% accuracy. Disk diffusion is
      cheaper than E-test (approximately 2.6 cents vs. 2.60 US dollars), is easy to
      perform, and is a reliable method for testing H. pylori susceptibility to
      antimicrobial agents in the clinical microbiology laboratory.

PMID- 16972132
TI  - Nucleotide polymorphism associated with ethambutol resistance in clinical
      isolates of Mycobacterium tuberculosis.
AB  - Ethambutol (EMB) is a first-line drug used for antitubercular therapy in
      combination with other drugs as recommended by World Health Organization
      DOTS/DOTS-Plus regimens. EMB is also effective in the treatment of opportunistic
      mycobacterial infections in patients with human immunodeficiency virus. The emb
      locus has been considered as a drug target for EMB, and substitutions of codon
      306 in Mycobacterium tuberculosis gene embB have been shown to be the most
      frequent and predictive mutations for EMB resistance. The aim of the present
      study was to detect embB and embC gene mutations in EMB-resistant clinical
      isolates. A total of 23 isolates of M. tuberculosis from patients with pulmonary
      tuberculosis were included in the study. Drug sensitivity was tested by
      proportion method and E-test. All 23 isolates were EMB resistant. Primers to
      amplify the embB and embC gene were designed, and polymerase chain reaction
      products were subjected for sequence analysis. H37Rv standard laboratory strain
      was used as control. Nucleotide sequencing showed that 16 strains had a mutation
      in the embB gene. The most common mutation observed in the embB gene was at codon
      306, followed by mutations at codons 299 and 378 in 4 and 2 isolates,
      respectively. Novel mutations have been reported at codons 239, 240, 247, 282,
      311, 368, 397, 446, 469, and 471. Sequence analysis of the embC gene showed
      mutation in 8 isolates at codon 270. Novel mutations in embC have been reported
      at codons 251 and 254. The most common nucleotide polymorphism in our isolates
      was at codons 306 and 299 in the embB gene and at codon 270 in the embC gene. A
      mutation at codon 306 was usually associated with high-level ethambutol
      resistance.

PMID- 16972133
TI  - A recombinant truncated Cry1Ca protein is toxic to lepidopteran insects and forms
      large cuboidal crystals in insect cells.
AB  - A truncated version of the cry1Ca gene from Bacillus thuringiensis was introduced
      into the genome of Autographa californica multiple nucleopolyhedrovirus (AcMNPV)
      under the control of two promoters. A recombinant virus (vSyncry1c) was isolated
      and used to infect insect cells in culture and insect larvae. Structural and
      ultrastructural analysis of insects infected with vSyncry1C showed the formation
      of large cuboidal crystals inside the cytoplasm of insect cells in culture and in
      insect cadavers late in infection. Infected insect cell extracts were analyzed by
      SDS-PAGE and Western blot and showed the presence of a 65-kDa polypeptide
      probably corresponding to the protease processed form of the toxin. Bioassays
      using purified recombinant toxin crystals showed a CL(50) of 19.49 ng/ml for
      2(nd) instar A. gemmatalis larvae and 114.1 ng/ml for S. frugiperda.

PMID- 16972134
TI  - Effects of carbon source and Vitreoscilla hemoglobin (VHb) on the production of
      beta-galactosidase in Enterobacter aerogenes.
AB  - At fixed concentration (0.5%), lactose and galactose acted as inducers while
      glucose and other tested carbon sugars showed repression effects on beta
      galactosidase production in Enterobacter aerogenes strain. The expression of
      Vitreoscilla hemoglobin gene (vgb) in this bacterial strain managed to overcome
      the repression effects as well as improving the induction of beta-galactosidase
      formation by carbon sources. In parallel, the bacterial O(2) consumption was
      increased correspondingly to the vgb induction of beta-galactosidase synthesis.
      When Enterobacter aerogenes strains were grown at the incubation temperature 42
      degrees C, about 5-fold higher enzyme productivity was obtained than with a
      similar incubation at 37 degrees C. The bacterial growth expressed as biomass
      yield had a different optimum temperature and was not influenced to the same
      extent by variations in the carbon sources. These data are discussed in terms of
      proposed enhancement in beta-galactosidase productivity by vgb expression as well
      as its significance to improve the technology of whey processing.

PMID- 16972135
TI  - Purification, characterization, and antifungal activity of chitinase from
      Streptomyces venezuelae P10.
AB  - Streptomyces venezuelae P(10) could produce extracellular chitinase in a medium
      containing 0.6% colloidal chitin that was fermented for 96 hours at 30 degrees C.
      The enzyme was purified to apparent homogeneity with 80% saturation of ammonium
      sulfate as shown by chitin affinity chromatography and DEAE-cellulose anion
      exchange chromatography. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) of the enzyme showed a molecular weight of 66 kDa. The
      chitinase was characterized, and antifungal activity was observed against
      phytopathogens. Also, the first 15 N-terminal amino-acid residues of the
      chitinase were determined. The chitin hydrolysed products were N
      acetylglucosamine and N, N'-diacetylchitobiose.

PMID- 16972136
TI  - Partial purification of proteinase K inhibitors from liquid-cultured mycelia of
      the white rot basidiomycete Trametes versicolor.
AB  - Novel protease inhibitors were isolated from liquid-cultured mycelia of the white
      rot fungus Trametes versicolor. Two bands of antiproteinase K activity, TvPI-A
      and TvPI-B, were detected in the crude cell extract by native polyacrylamide gel
      electrophoresis (PAGE). Proteins corresponding to TvPI-A were purified by heat
      treatment, anion-exchange chromatography, and gel filtration. Sodium dodecyl
      sulfate (SDS)-PAGE demonstrated the presence of three proteins with molecular
      masses of 14.5, 16.6, and 20 kDa, respectively. T. versicolor protease inhibitors
      suppressed the activity of proteinase K and, to a smaller extent, of Carlsberg
      subtilisin, whereas trypsin and chymotrypsins were not inhibited. The inhibitors
      were acidic proteins and showed remarkable heat stability. To our knowledge, this
      is the first report about proteinase K inhibitors from fungi.

PMID- 16972137
TI  - Stochastic modeling predictions for the clearance of insoluble particles from the
      tracheobronchial tree of the human lung.
AB  - Bronchial clearance of deposited particles was simulated using a stochastic model
      of the tracheobronchial tree. The clearance model introduced in this study
      considers (1) a continuous decrease of the mucus thickness from the trachea to
      the terminal bronchioles according to a linear or an exponential function, (2)
      the possibility of mucus discontinuities, which are mainly found in intermediate
      and distal airways of the tracheobronchial compartment, (3) mucus production in
      proximal airways, (4) a slow bronchial clearance phase due to the capture of a
      defined particle fraction f (s) in the periciliary sol phase, and (5) an eventual
      delay of the mucociliary transport at carinal ridges of airway bifurcations.
      Based on the concept of mucus volume conservation in single bifurcations, a
      reduction of the thickness of the mucus blanket from proximal to distal airways
      causes a significant increase of the mucus velocities in small ciliated airways
      compared to other stochastic modeling predictions assuming a constant thickness
      of the mucus layer throughout the conducting airways. This effect is further
      enhanced by the consideration of mucus discontinuities. In contrast, the ability
      of bronchial airways to produce a certain volume of mucus has a decreasing effect
      on the mucus velocities. In all generated clearance velocity models, mucociliary
      clearance is completely terminated within 24 h after exposure, consistent with
      the experimental evidence. Implementation of a slow bronchial clearance phase
      predicts a long-term retention fraction, which is fully cleared from the lung
      after several weeks. For 1-microm MMAD particles, 24-h retention varies between
      0.42 and 0.52, in line with the suggestions of the ICRP. Mucus delay at carinal
      ridges only affects short-term clearance by increasing the retained particle
      fraction at a given time, while long-term retention is not influenced.

PMID- 16972138
TI  - A stand against expectant management of anal dysplasia.

PMID- 16972141
TI  - Kinase activity and subcellular distribution of a chimeric green fluorescent
      protein-tagged Janus kinase 2.
AB  - Janus kinase 2 (JAK2) is an essential intracellular signal transducer for
      numerous cytokines and hormones. To examine how JAK2 structural modifications can
      affect cellular physiology, we created expression vectors for chimeric proteins
      containing an enhanced green fluorescent protein (EGFP) fused to rat JAK2
      (EGFP/rJAK2), and a kinase-inactive variant, EGFP/rJAK2(K882E). The properties of
      EGFP/rJAK2 were examined following transient transfection of COS-7 cells.
      EGFP/rJAK2 was expressed throughout the cell, and was found in subcellular
      membrane, cytosolic and nuclear fractions. Interestingly, EGFP/rJAK2
      phosphorylated other proteins in situ without additional cytokine stimulation.
      Furthermore, despite a much higher level of tyrosine phosphorylation arising from
      in situ autophosphorylation, the in vitro radiolabelling autokinase activity of
      EGFP/rJAK2 was significantly less than that of the endogenous JAK2. These results
      reveal a technical limitation of the application of the "conventional" in vitro
      radiolabelling autokinase assay to hyperphosphorylated forms of the enzyme and
      illustrate the potential weaknesses in individual assays commonly used to
      determine JAK2's enzymatic activity and subcellular distribution. We also suggest
      that the EGFP/rJAK2 model can be very useful in studying JAK2-related cancers,
      because its ubiquitous distribution and abnormal constitutive
      hyperphosphorylation may distinguish it from the cytokine-regulated, membrane
      proximal form of JAK2 associated with normal physiology.

PMID- 16972140
TI  - A novel matrix protein p10 from the nacre of pearl oyster (Pinctada fucata) and
      its effects on both CaCO3 crystal formation and mineralogenic cells.
AB  - A novel matrix protein, designated as p10 because of its apparent molecular mass
      of 10 kDa, was isolated from the nacreous layer of pearl oyster (Pinctada fucata)
      by reverse-phase high-performance liquid chromatography. In vitro crystallization
      experiments showed that p10 could accelerate the nucleation of calcium carbonate
      crystals and induce aragonite formation, suggesting that it might play a key role
      in nacre biomineralization. As nacre is known to contain osteogenic factors, two
      mineralogenic cell lines, MRC-5 fibroblasts and MC3T3-E1 preosteoblasts, were
      used to investigate the biological activity of p10. The results showed that p10
      could increase alkaline phosphatase activity, an early marker of osteoblast
      differentiation, while the viability of MRC-5 and MC3T3-E1 remained unchanged
      after treatment of p10. Taken together, the findings led to identification of a
      novel matrix protein from the nacre of P. fucata that plays a role in both the
      mineral phase and in the differentiation of the cells involved in
      biomineralization.

PMID- 16972142
TI  - Repeatability of nerve conduction measurements using automation.
AB  - OBJECTIVE: To quantify nerve conduction study (NCS) reproducibility utilizing an
      automated NCS system (NC-stat, NeuroMetrix, Inc.). METHOD: Healthy volunteers
      without neuropathic symptoms participated in the study. Their median, ulnar,
      peroneal, and tibial nerves were tested twice (7 days apart) by the same
      technician with an NC-stat instrument. Pre-fabricated electrode arrays specific
      to each nerve were used. Both motor responses (compound motor action potential
      [CMAP] and F-waves - all nerves) and sensory responses (sensory nerve action
      potentials [SNAP] - median and ulnar nerves only) were recorded following
      supramaximal stimuli. Automated algorithms determined all NCS parameters: distal
      motor latency (DML), mean F-wave latency (FWL), distal sensory latency (DSL),
      CMAP amplitude, and SNAP amplitude. Latency was adjusted for skin temperature
      deviation from reference. Pearson correlation coefficient (CC), intraclass
      correlation coefficient (ICC), coefficient of variance (CoV), and relative
      intertrial variation (RIV) were calculated. RESULTS: Fifteen subjects
      participated in either upper or lower extremity studies with nine participating
      in both. With the exception of CMAP amplitude, all parameters had CoV less than
      0.06. Upper extremity amplitude parameters had CCs greater than 0.85. CCs for
      latencies were greater than 0.80 except for the median nerve FWL (CC = 0.69). For
      lower extremity nerves, ICCs were highest for mean FWL (>0.90), followed by DML
      (>0.82) and then CMAP (peroneal 0.33, tibial 0.73). The 10th to 90th RIV
      percentiles were bounded by +/-7% for F-wave latencies; +/- 9% for all DSLs; and
      +/- 11% for DML (except peroneal at 15%). CONCLUSIONS: The reproducibility of NCS
      parameters obtained with an automated NCS instrument compared favorably with
      traditional electromyography laboratories. F-wave latencies had the highest
      repeatability, followed by DML, DSL, SNAP and CMAP amplitude. Given their high
      reproducibility, automated NCS instrument may encourage wider utilization of NCS
      in clinical and research applications.

PMID- 16972143
TI  - Cardiovascular magnetic resonance in a pregnant patient with absent pulmonary
      valve syndrome.
AB  - We present a 22 year old Moroccan woman with chronic severe pulmonary
      regurgitation, who becomes symptomatic in her fourth month of pregnancy.
      Cardiovascular magnetic resonance, during pregnancy, revealed a large pulmonary
      aneurysm and turbulent blood flow in the pulmonary trunk with severe pulmonary
      regurgitation. After gestation, the branch pulmonary arteries were assessed with
      magnetic resonance angiography and the severely dilated pulmonary arterial trunk
      and valve were replaced by a pulmonary homograft. We briefly review this rare
      syndrome, the management of pulmonary regurgitation during pregnancy and the role
      of CMR during pregnancy.

PMID- 16972144
TI  - Tei index in adult patients submitted to adriamycin chemotherapy: failure to
      predict early systolic dysfunction. Diagnosis of adriamycin cardiotoxicity.
AB  - AIMS: This study prospectively assessed whether Tei index is predictive of early
      systolic dysfunction in adults undergoing adriamycin treatment. METHODS AND
      RESULTS: Left ventricular ejection fraction (LVEF) was obtained by radionuclide
      ventriculography at baseline and after treatment. Tei index was evaluated by
      echocardiography at baseline, at an intermediary cycle and at the end of
      chemotherapy. Fifty-five predominantly female patients (91%) with breast cancer
      (80%) and without known cardiac disease were evaluated. After treatment
      (adriamycin dose of 304 +/- 47 mg/m(2)), systolic dysfunction (final LVEF < 50%)
      occurred in eight patients (14%). Baseline, intermediate or variation of Tei
      index were not accurate to predict early systolic dysfunction ("c" statistics <
      or = 0.60). Baseline Tei index > 0.39, for example, had a sensitivity of 75%,
      specificity of 55%, positive predictive value of 22% and negative predictive
      value of 93%. CONCLUSION: Tei index does not appear to be a useful tool for
      detection of early adriamycin cardiotoxicity in adults.

PMID- 16972145
TI  - Will the real left ventricular volume please stand up?

PMID- 16972146
TI  - Use of noninvasive tools in primary pulmonary hypertension to assess the
      correlation of right ventricular function with functional capacity and to predict
      outcome.
AB  - Most patients with Primary Pulmonary Hypertension (PPH) have severe exertional
      limitation which ultimately leads to right heart failure and death. The purpose
      of the study was to assess the correlation between right ventricular (RV)
      systolic and diastolic noninvasive variables and exercise tolerance, as well as
      the predictors of adverse outcome in treated patients. METHODS: We prospectively
      studied 29 patients, 17 with PPH and 12 with PPH due to collagen disease. RV
      parameters were assessed by echocardiography and Radionuclide ventriculography.
      Pulmonary function and clinical profile were assessed by 6 min walk test and NYHA
      class. The patients were followed-up during 2 years for cardiac death and cardiac
      deterioration. RESULTS: Mean age was 51 +/- 15 years, 22 (78%) women. NYHA class1
      in 2 pts, class 2 in 17, class 3 in 8 and class 4 in 2 pts. Pulmonary function
      (DLCO) was low in 25 (86%) pts, mean 22 +/- 48%. Six minutes walk distance was
      358 +/- 132 m, RVEF was 34 +/- 11% (range 16-51%). Among RV variables, RVEF, RA
      area and TR were independently correlated to 6 min walk. Within follow up of 2
      years, there were 10 patients with adverse outcome (4 deaths and 6 deteriorated
      to NYHA class 3 and 4). Among all clinical and noninvasive variables, RVEF only
      was correlated to adverse outcome. CONCLUSION: The noninvasive tests of RVEF, RA
      size and TR were closely correlated to exercise tolerance. However, among the
      various clinical, functional and RV variables, RVEF was the only variable
      correlated with adverse outcome in pts with PPH.

PMID- 16972147
TI  - Systo-diastolic ventricular function in patients with hypertension: an
      echocardiographic tissue doppler imaging evaluation study.
AB  - BACKGROUND: Tissue Doppler imaging (TDI) has evolved to become a useful non
      invasive method that can complement other echocardiographic techniques in the
      assessment of left ventricular function in different clinical conditions.
      Spectral pulsed TDI can provide measurements of regional systolic and diastolic
      myocardial velocities and is particularly useful in detecting abnormalities of
      left ventricular systolic and diastolic function. We investigated the presence of
      systo-diastolic dysfunction in patients (pts) with hypertension compared with pts
      affected by hypertensive cardiomyopathy and normal control subjects. METHODS: We
      evaluated 214 pts with traditional echocardiography and TDI: 69 normal control
      subjects (Group A); 145 pts with hypertension, divided according to base
      echocardiographic evaluation in 74 with no evidence of hypertensive
      cardiomyopathy (diastolic dysfunction and ventricular hypertrophy, Group B), and
      71 with evidence of hypertensive cardiomyopathy (Group C). Pts groups were
      matched for age, sex, heart rate, smoking status and body surface area. RESULTS:
      There were no significant differences in ventricular diameters, volumes,
      shortening and ejection fraction values; TDI showed a progressive systolic wave
      peak reduction from Group A to B and from Group B to C. Routinely Doppler
      diastolic function did not show any significant difference between Group A and B;
      TDI showed progressive E wave peak velocity decrease and A wave peak velocity
      increase from Group A to B and C and from Group B to C. CONCLUSIONS: TDI
      evaluation showed a ventricular systolic dysfunction in pts with hypertensive
      cardiomyopathy; in addition, an early mild systo-diastolic dysfunction was
      detected in subjects with hypertension but no evidence of hypertensive
      cardiomyopathy.

PMID- 16972148
TI  - An important but easily forgettable review: extracardiac activity in myocardial
      perfusion scans.

PMID- 16972149
TI  - Myocardial perfusion abnormalities in chemical warfare patients intoxicated with
      mustard gas.
AB  - BACKGROUND: Mustard agents are of the major chemical agents used during Iran-Iraq
      war. There are no reports concerning long-term cardiac effects. The aim was to
      assess the scintigraphic pattern of myocardial perfusion in patients intoxicated
      with blistering gases. METHOD: We analyzed myocardial perfusion scans of 22
      consecutive intoxicated patients (21 male and 1 female, all < 44 years) and
      compared results with 14 controls. Only those patients and controls were entered
      whose 10-year risk of coronary artery disease (Framingham criteria) was <5%. Also
      only those patients were experimented upon that had currently other confirmed
      complications of intoxication (respiratory, cutaneous and ocular complications).
      All patients underwent a 1-day stress and rest protocol using (99m)Tc-MIBI.
      Images were assessed visually and quantitatively using Cedars Sinai program.
      RESULTS: The prevalence of nonhomogeneity of uptake and left and right
      ventricular enlargement in both visual and quantitative analyses were higher in
      the mustard exposed patients than unexposed controls. The prevalence of ischemia
      was higher in the exposed patients (P < 0.05). Cavity to myocardium ratio, as an
      established and validated measure of ejection fraction, was also significantly
      lower in the warfare patients than the controls. CONCLUSION: In so far it lies in
      our knowledge, this is the first report concerning the scintigraphic pattern of
      myocardial perfusion in mustard intoxicated patients. Based on the results, the
      pattern of myocardial perfusion in these patients is significantly different from
      normal controls, which could resemble either coronary artery disease or mild
      cardiomyopathic changes.

PMID- 16972150
TI  - Emergent robustness in competition between autocatalytic chemical networks.
AB  - The origin of auto-catalytic networks has been proposed as an initial step in pre
      biotic evolution. It is possible to derive simple models where auto-catalytic
      networks naturally arise from simple chemical mixtures. In order for such a
      system to develop, there needs to be some degree of stability, what is
      characterised as ;robustness'. We demonstrate that competing systems generate
      this robustness as they create a distributed network of catalytic pathways.

PMID- 16972151
TI  - Ribosome origins: the relative age of 23S rRNA Domains.
AB  - The modern ribosome and its component RNAs are quite large and it is likely that
      at an earlier time they were much smaller. Hence, not all regions of the modern
      ribosomal RNAs (rRNA) are likely to be equally old. In the work described here,
      it is hypothesized that the oldest regions of the RNAs will usually be highly
      integrated into the machinery. When this is the case, an examination of the
      interconnectivity between local RNA regions can provide insight to the relative
      age of the various regions. Herein, we describe an analysis of all known long
      range RNA/RNA interactions within the 23S rRNA and between the 23S rRNA and the
      16S rRNA in order to assess the interconnectivity between the usual Domains as
      defined by secondary structure. Domain V, which contains the peptidyl transferase
      center is centrally located, extensively connected, and therefore likely to be
      the oldest region. Domain IV and Domain II are extensively interconnected with
      both themselves and Domain V. A portion of Domain IV is also extensively
      connected with the 30S subunit and hence Domain IV may be older than Domain II.
      These results are consistent with other evidence relating to the relative age of
      RNA regions. Although the relative time of addition of the GTPase center can not
      be reliably deduced it is pointed out that the development of this may have
      dramatically affected the progenotes that preceded the last common ancestor.

PMID- 16972152
TI  - Dracunculus mulbus n. sp. (Nematoda: Spirurida) from the water python Liasis
      fuscus (Serpentes: Boidae) in northern Australia.
AB  - A new species of Dracunculus Reichard, 1759 (Nematoda: Spirurida) is described
      from the tissues surrounding organs in the body-cavity of the water python Liasis
      fuscus Peters in northern Australia. One to 14 worms were recovered from 22%
      (27/120) of pythons examined. Males were located principally around the lungs,
      liver and heart of the hosts, and females were recovered from peritoneal tissue
      surrounding the intestines and lining the body-cavity. This species differs from
      previously described species of Dracunculus in the position of the papillae at
      the posterior end in males, and in the possession of thick, narrow caudal alae.
      Submedian cephalic papillae are single in both sexes. Dorsal and ventral anterior
      cephalic papillae are absent in males. This is the first report of a species of
      Dracunculus from the Australian region.

PMID- 16972153
TI  - Parasite biodiversity in a coral reef fish: twelve species of monogeneans on the
      gills of the grouper Epinephelus maculatus (Perciformes: Serranidae) off New
      Caledonia, with a description of eight new species of Pseudorhabdosynochus
      (Monogenea: Diplectanidae).
AB  - Coral reefs are known for their high level of biodiversity, but parasite
      biodiversity has not been evaluated. Cases such as Epinephelus maculatus,
      described here, show that the numerical estimation of parasite biodiversity in
      coral reefs could reach more than ten times the number of fish species;
      consequently, the extinction of certain fish species from endangered coral reefs
      would result in the co-extinction of at least ten times the number of parasite
      species. E. maculatus is a grouper of intermediate size (1-2 kg) and common in
      the coral reefs of New Caledonia, South Pacific. Based on the examination of more
      than 800 monogenean specimens, 12 species of monogeneans (ten diplectanids and
      two ancyrocephalids) were differentiated on the gills. These species of
      diplectanids have not been found in other epinephelines in the same area and thus
      are considered as specific to this host. In addition, three species of copepods,
      and isopod larvae, are present on the gills; E. maculatus thus has a total of 16
      species of gill ectoparasites, which can be found together on a single individual
      fish. Diplectanids include Laticola dae Journo & Justine, 2006, which is the most
      abundant species representing about 50% of the specimens, and nine species which
      are rare, each representing 2-7% of the specimens: Diplectanum uitoe n. sp. and
      eight species of Pseudorhabdosynochus Yamaguti, 1958. D. uitoe, provisionally
      attributed to Diplectanum Diesing, 1858, is characterised by a small conical
      penis with internal walls. Pseudorhabdosynochus auitoe n. sp., P. buitoe n. sp.,
      P. cuitoe n. sp., P. duitoe n. sp., P. euitoe n. sp. and P. fuitoe n. sp. are
      differentiated on the basis of the morphology of the sclerotised vagina, but are
      very similar in other characteristics; P. guitoe n. sp. is characterised by a
      quadriloculate organ with very thick walls and a very small sclerotised vagina;
      and P. huitoe n. sp. is characterised by its sclerotised vagina and by very long
      ventral and dorsal haptoral bars. Two rare (2-3% of specimens) ancyrocephalids,
      Haliotrema epinepheli Young, 1969 and Haliotrema sp., are briefly described in
      relation to the male copulatory organs and haptoral bars; H. epinepheli is
      apparently a generalist species found in various epinephelines and other fish
      species. A table of the 50 species of diplectanids (Pseudorhabdosynochus,
      Laticola Yang et al., 2006, Echinoplectanum Justine & Euzet, 2006 and
      Diplectanum) from serranids is provided.

PMID- 16972154
TI  - Neotropical Monogenoidea. 50. Oviparous gyrodactylids from loricariid and
      pimelodid catfishes in Brazil, with the proposal of Phanerothecioides n. g.,
      Onychogyrodactylus n. g. and Aglaiogyrodactylus n. g. (Polyonchoinea:
      Gyrodactylidea).
AB  - The diagnosis of Phanerothecium Kritsky & Thatcher, 1977 is amended, and
      Phanerothecioides n. g., Onychogyrodactylus n. g. and Aglaiogyrodactylus n. g.,
      all comprised of oviparous gyrodactylids (Monogenoidea: Polyonchoinea), are
      proposed to accommodate 11 of the 15 species (14 new to science) herein described
      and/or reported from loricariid and pimelodid catfishes (Teleostei: Siluriformes)
      in Brazil: Phanerothecium harrisi Kritsky & Boeger, 1991, P. spinatoides n. sp.
      and P. deiropedeum n. sp. all from Hypostomus spp.; P. spinulatum n. sp. from
      Hypostomus cf. regani; Phanerothecioides agostinhoi n. g., n. sp. (type-species)
      from Hypostomus spp. and Pseudoplatystoma fasciatum; Onychogyrodactylus sudis n.
      g., n. sp. (type-species) and O. hydaticus n. sp. both from Ancistrus
      multispinus; Aglaiogyrodactylus forficulatus n. g., n. sp. (type-species) from
      Kronichthys lacerta; A. pedunculatus n. sp. from Hisonotus sp.; A. guttus n. sp.
      from Pseudotothyris obtusa; A. salebrosus n. sp., A. conei n. sp. and A.
      ctenistus n. sp. all from Pareiorhaphis parmula; and A. calamus n. sp. and A.
      forficuloides n. sp. both from Schizolecis guntheri. Phanerothecioides n. g. is
      characterised by oviparous forms lacking superficial and deep haptoral bars and
      pregermarial vitelline follicles, and by having a conspicuous testis in adult
      specimens, a syncytial prostatic gland, a reduced copulatory sac and vitelline
      ducts in the form of an inverted 'U'. Onychogyrodactylus n. g. is differentiated
      from all other oviparous gyrodactylid genera by its members having a spine-like
      accessory sclerite enclosed in a separate pouch associated with the terminal male
      genitalia. Species of Aglaiogyrodactylus n. g. possess H-shaped vitelline ducts
      and a complex accessory piece and sclerotised or non-sclerotised male copulatory
      organ enclosed within the copulatory sac.

PMID- 16972155
TI  - Inflammation, genes and zinc in ageing and age-related diseases.
AB  - Lifelong antigenic burden determines a condition of chronic inflammation, with
      increased lymphocyte activation and pro-inflammatory cytokine production. A large
      number of studies have documented changes in Zn metabolism in experimental animal
      models of acute and chronic inflammation and in human chronic inflammatory
      diseases. In particular, modification of zinc plasma concentration as well as
      intracellular disturbance of antioxidant intracellular pathways have been found
      associated to age-related inflammatory diseases, like atherosclerosis. Zinc
      deficiency is extremely diffused in aged people that are educated to avoid meat
      and other high Zn-content foods due to fear of cholesterol. Rather, they increase
      consumption of refined wheat products that lack of Zn, magnesium and other
      critical nutrients in consequence of refining process. On the other hand, plasma
      concentration of metallic ions like Zn is influenced by pro-inflammatory
      cytokines production. A major target of Zn may be NF-kB, a transcription factor
      critical for the expression of many pro-inflammatory cytokines whose production
      is finely regulated by extra- and intracellular activating and inhibiting factors
      interacting with regulatory elements on cytokine genes. Moreover, this factor is
      regulated by the expression of specific cellular genes involved in inflammation.
      So it is not surprising that Zn deficiency is constantly observed in aged
      patients affected by infectious diseases. On the other hand, cytokine genes are
      highly polymorphic and some of these polymorphisms have been found associated to
      age-related diseases as atherosclerosis. Therefore, Zn deficiency in individuals
      genetically predisposed to a dis-regulation of inflammation response, may play a
      crucial role, in causing adverse events and in reducing the probability of a
      successful aging.

PMID- 16972156
TI  - The impact of newly diagnosed chronic paediatric conditions on parental quality
      of life.
AB  - OBJECTIVE: Parental functioning and well-being are important aspects of a
      family's adaptation to chronic paediatric conditions. This study investigates the
      effects of diagnosis (cancer vs. diabetes/epilepsy) and time since diagnosis on
      parental quality of life (PQL). METHODS: 122 parents (66 mothers, 56 fathers),
      whose children were diagnosed and treated for one chronic disease, filled in the
      Ulm Quality of Life Inventory for Parents twice within the first three months
      after the initial diagnosis. The effects of diagnosis and time (1-2 weeks and 2-3
      months after diagnosis) on PQL were analysed separately for mothers and fathers.
      RESULTS: Parents of a child with cancer consistently reported lower PQL compared
      with parents of a child with diabetes/epilepsy. Only the fathers' well-being
      increased significantly within the first three months after the child was
      diagnosed for a chronic disease. However, in most of the PQL domains there was a
      persistent impairment within the time-frame of this study. Parents of children
      with a chronic disease were more satisfied with their family situation than
      healthy controls. Age of the child was positively correlated with PQL.
      CONCLUSIONS: A diagnosis of cancer, especially in young children, has a strong
      negative effect on PQL. Measuring PQL in a preventive approach would help to
      identify vulnerable parents and to provide psychosocial support in time.

PMID- 16972157
TI  - Predicting general well-being from self-esteem and affectivity: an exploratory
      study with Scottish adolescents.
AB  - The present study investigated the association between the personality constructs
      of self-esteem/affectivity and General Well-Being (GWB) in Scottish adolescents.
      A total of 425 secondary school pupils completed the P.G.I. General Well-Being
      Scale [Verma et al. Ind J. Clin. Psychol. 10 (1983) 299], the Hare Self-esteem
      Scale (HSES) [Hare, The Hare General and Area-Specific (School, Peer, and Home)
      Self-esteem Scale. Unpublished manuscript, Department of Sociology, SUNY Stony
      Brook, New York, mineo, 1985] and the Positive and Negative Affect Schedule
      (PANAS) [Watson et al. J Personal Soc Psychol 54 (1988a) 1063]. Combined self
      esteem, positive and negative affectivity, age and gender accounted for 49.7% of
      the total GWB variance, 24.9% of the physical well-being variance, 41.6% of the
      mood/affect well-being variance, 33.3% of the anxiety well-being variance and
      44.3% of the self/others well-being variance. Home self-esteem was found the
      strongest predictor of mood/affect and self/others well-being domains as well as
      well-being total. It was also the second best predictor of anxiety well-being
      domain. School self-esteem was the strongest predictor of physical well-being,
      whereas negative affectivity was the strongest predictor of anxiety well-being
      domain. However age and gender were not significantly associated with GWB, total
      or domain specific. The study adds to previous evidence regarding the high
      association between GWB and personality factors in adult and adolescent
      populations. Directions for future research are discussed.

PMID- 16972158
TI  - Condensation and validation of a 4-item index of the Acne-QoL.
AB  - BACKGROUND: The 19-item Acne-QoL is a validated psychometric instrument designed
      for use in clinical trials. OBJECTIVE: The purpose of this study was to develop a
      condensed version of the Acne-QoL as an alternative measure of psychosocial
      impact for use in routine clinical practice. METHODS: Four condensed versions of
      the Acne-QoL were evaluated by regression analysis in a subset of 434 patients.
      The version with four items most broadly representative of acne-specific quality
      of life combined with a high level of correlation to Acne-QoL total score was
      selected for further validation in two different patient samples. RESULTS: The
      patient ranked condensation, representing items from each domain of greatest
      patient-perceived importance and relevance was selected for further analysis
      (Acne-Q(4)). The Acne-Q(4) explained 98.5% of the variation in total score of
      Acne-QoL. Validation of the Acne-Q(4) in a follow-up group and an independent
      subset of patients resulted in Pearson correlation coefficients of 0.967
      (p<0.001). Construct validity of the Acne-Q(4) was confirmed by demonstrating a
      similar relationship as the Acne-QoL to acne severity. LIMITATIONS: There is less
      breadth and detail of QoL information in the Acne-Q(4) than in the Acne-QoL. The
      analysis relied on a total score for Acne-QoL, which the original developers did
      not validate. CONCLUSIONS: The Acne-Q(4) is accurately reflective of the parent
      instrument and may facilitate the psychometric evaluation of the impact of facial
      acne on patients in routine clinical practice by its practicality.

PMID- 16972159
TI  - Issues in conducting cross-cultural research: implementation of an agreed
      international protocol [corrected] designed by the WHOQOL Group for the conduct
      of focus groups eliciting the quality of life of older adults.
AB  - Multi-centre and cross-cultural research require the use of common protocols if
      the results are to be either pooled or compared. All too often adherence to
      protocols is not discussed in reports and where it is reported poor adherence is
      frequently noted. This paper discusses the use of international guidelines
      developed by WHOQOL Field Centres to conduct and report focus groups aimed at
      eliciting key concepts of quality of life among older adults. This was the first
      step in the development of the WHOQOL-OLD instrument. Although there was overall
      adherence to the agreed guidelines, there were some differences in the level of
      reporting, even after participating Field Centres had the opportunity to explain
      their reports. The reasons for these discrepancies are reported. It is concluded
      that because of local situations, it is difficult to achieve identical
      implementation of multi-centre cross-cultural protocols and that the highest
      standards of auditing are required if findings are to be compared. Suggestions
      for how such protocols can be improved are given.

PMID- 16972160
TI  - Measuring health-related quality of life in bipolar disorder: relationship of the
      EuroQol (EQ-5D) to condition-specific measures.
AB  - Generic utility measures of health-related quality of life provide an independent
      net valuation of health states. They are increasingly used with condition
      specific outcome measures in assessing treatments. In Bipolar Disorder, a few
      studies indicate poorer quality of life for depressed vs. euthymic patients. A
      single study suggests mania is less negative than depression. This analysis
      examines the relationship of one such scale, the EuroQol (EQ-5D), to objective
      and subjective measures of depression and mania in 221 Bipolar subjects, recently
      or still in an episode of illness. RESULTS: Depressed patients showed a very poor
      quality of life (median EQ-5D Index score 0.41). Index and Visual Analogue scores
      improved significantly as level of depression decreased (Jonckheere-Terpstra test
      p<0.001). Both scores were significantly negatively related to all depression
      measures. Patients reported problems across all areas of life covered by the EQ
      5D. No such relationships were observed between EQ-5D scores and mania measures,
      though all mania measures were inter-related. However, the range of mania shown
      was quite restricted. CONCLUSIONS: The EQ-5D is a useful measure of quality of
      life for Bipolar patients suffering from depression. Conclusions about the role
      of the EQ-5D in mania are restricted by the limited range of mania observed.

PMID- 16972161
TI  - Initial validation of the Swedish version of the London Handicap Scale.
AB  - OBJECTIVE: To adapt and evaluate the unweighted version of the London Handicap
      Scale (LHS) for use in Sweden. MATERIALS & METHODS: Respondent burden, linguistic
      validity and patient perceived relevance was assessed in 16 neurologically ill
      patients. Internal consistency reliability and construct validity were evaluated
      among 89 stroke survivors six months after discharge. RESULTS: Patients perceived
      the LHS as relevant and easy to understand and complete. Mean time to complete
      the questionnaire was 10 min. Cronbach's alpha reliability was 0.85. The LHS
      differentiated between patients living at home and in special accommodations. As
      expected, scores correlated strongly and weakly with indices of related and more
      remote constructs, respectively. There were no floor-, but large ceiling effects.
      CONCLUSIONS: The observations reported here are in accordance with previous
      studies using the original British LHS and provide initial support for the
      reliability and validity of the instrument for use in Sweden. However, ceiling
      effects may limit its usefulness as an outcome measure.

PMID- 16972162
TI  - Using GI-specific patient outcome measures in renal transplant patients:
      validation of the GSRS and GIQLI.
AB  - INTRODUCTION: Gastrointestinal (GI) side-effects occur frequently as a result of
      immunosuppressant regimens used in renal transplant patients. Little effort has
      been made to quantify the impact of these side-effects on patients' health
      related quality of life and symptom severity. OBJECTIVE: To assess the
      psychometric characteristics of two GI-specific outcome instruments (the
      Gastrointestinal Rating Scale (GSRS) and the Gastrointestinal Quality of Life
      Index (GIQLI)) for use in post-renal transplant patients. METHODS: Cross
      sectional study conducted at 5 clinical centers in 4 countries. Patients were
      required to be on mycophenolate mofetil and a calcineurin inhibitor. Patients
      completed the GSRS, GIQLI and two generic instruments (the Psychological General
      Well-Being Index and the EQ-5D) at one timepoint. Reliability, construct and
      known groups validity were assessed. RESULTS: In general the GSRS and the GIQLI
      demonstrated Cronbach's alphas higher than 0.70. The GIQLI was moderately to
      highly correlated with the PGWB and EQ-5D. Correlations among the GSRS and
      generic instruments were slightly lower. The GSRS and GIQLI both distinguished
      between patients with and without GI complaints (all p<0.05). CONCLUSIONS: The
      GSRS and the GIQLI are appropriate for use in a post-renal transplant population.
      Scores on both instruments demonstrated significant differences between renal
      transplant patients with GI complications and without GI complications.

PMID- 16972163
TI  - Feasibility and validity of a computer administered version of SEIQoL-DW.
AB  - Computer administrered QoL instruments are increasingly used to assess outcomes.
      Our aim was to assess the feasibility and validity of an electronic version of
      the SEIQoL-DW. Pharmacy students (n = 40; mean age 25; 92% women) were
      administrated both the touch screen and the paper-and-pen versions in a cross
      over study. The majority of the students (65 %) preferred the computer version,
      while almost a third (27%) preferred the paper and pen version. There was no
      overall order effect and the SEOQoL-DW index mean scores differed with 1.2
      between the two versions. Those respondents completing the computer version first
      had higher scores than those completing the computer version second. The ICC
      comparing the formats was 0.77 (CI: 0.57-0.88) and the limits of agreement method
      showed that 85% of the observations were within +/- 1-10 units. Most students
      (82%) judged their QoL as being equivalent to their SEIQoL-DW score. The computer
      version of the SEIQoL-DW seems to be feasible and acceptable and seems to be
      valid alternative to the paper and pen version. However, further validation
      studies in larger patient populations are needed.

PMID- 16972164
TI  - Health-related quality of life in youth with epilepsy: theoretical model for
      clinicians and researchers. Part I: the role of epilepsy and co-morbidity.
AB  - Children and adolescents with epilepsy are at increased risk for poor health
      related quality of life (HRQL) even in the absence of active seizures. Clinicians
      who aim to achieve optimal seizure control also need to focus on improving HRQL.
      This can only be accomplished by recognizing how different features of the
      epilepsy itself, co-morbid conditions, as well as psychosocial factors can all
      make a difference to HRQL. These psychosocial factors include child, family and
      community/society variables that play a role in the well-being of these children.
      Conceptual models are relevant insofar as they provide us with a basis for
      hypothesizing the causal processes that lead to improved HRQL. They delineate
      what is meant by HRQL and highlight factors relevant to this important outcome.
      Researchers can use such models to test statistically and clinically relevant
      relationships. Clinicians can use this knowledge to direct the planning and
      implementation of services that are informed by these relationships, critically
      evaluate and then choose HRQL measures for use in clinical practice that most
      closely approximate what they understand HRQL is. The purpose of this review is
      to identify what is meant by HRQL as well as outline the theoretical and
      empirical basis for what it is about epilepsy, co-morbidity, and its treatment
      that we believe make a difference to HRQL.

PMID- 16972165
TI  - Exploiting the wild crucifer Thlaspi arvense to identify conserved and novel
      genes expressed during a plant's response to cold stress.
AB  - Thlaspi arvense, a wild species from the Brassicaceae family, was shown to have a
      higher level of freezing tolerance than either of its close relatives, the model
      plant Arabidopsis thaliana or the crop Brassica napus (canola). Over 600 clones
      were sequenced from a subtractive cDNA library generated from cold treated T.
      arvense tissue, establishing that T. arvense shared significant sequence identity
      with both A. thaliana and B. napus (90-92%). In light of the strong sequence
      similarity between T. arvense and A. thaliana and to exploit the available
      genomics resources for Arabidopsis, the efficacy of using long 70 mer
      oligonucleotide whole genome Arabidopsis microarrays was tested for T. arvense.
      Gene expression in T. arvense leaf tissue during the very early stages of cold
      acclimation (or cold stress) was assayed at three time points and compared to an
      untreated control. This analysis highlights some of the difficulties and benefits
      of using cross-species microarray analysis. The data suggested that T. arvense
      responds in a similar fashion to cold stress as the model plant A. thaliana.
      However, for a number of genes quantitative differences in the level and timing
      of expression were identified. One of the most notable differences suggested that
      sulphur assimilation leading to the increased production of the methyl donor S
      adenosyl-methionine was playing a role in the response of T. arvense to cold
      stress.

PMID- 16972166
TI  - The FEATHERED gene is required for polarity establishment in lateral organs
      especially flowers of the Japanese morning glory (I pomoea nil ).
AB  - Most strains harboring the feathered (fe) mutation in the Japanese morning glory
      (Ipomoea nil or Pharbitis nil) show deformed phenotypes such as upcurled leaves
      and separated or tubular petals. These phenotypes seem to be caused by loss of
      abaxial identity in lateral organs. The FE gene was isolated using the inserted
      transposon as a tag. An En/Spm-related transposable element, Tpn102, inserted in
      the fourth intron of the FE gene, was responsible for the fe mutation. FE encodes
      a GARP transcription factor closely related to Arabidopsis KANADI1 (KAN1), which
      promotes an abaxial cell fate. Genetic analyses and molecular studies, which
      showed that all fe mutant strains have the same fe allele despite their
      phenotypic differences, revealed that fe strains with strong phenotypes have
      additional mutations enhancing the fe phenotype. These findings and historical
      records of fe phenotypes suggest that these enhancer mutations were accumulated
      in the fe background during selection for strong phenotypes. The mutant
      phenotypes and molecular analysis of fe strains suggest that FE regulates the
      abaxial identity of lateral organs redundantly with modifier genes, as KAN1 does
      in Arabidopsis. FE, however, affects flower phenotype even in the single mutant
      unlike KAN1, moreover, modifier mutations affect flower phenotype only in the fe
      mutant background, suggesting that FE may play a more crucial role in promotion
      of abaxial cell fate in flowers of the Japanese morning glory.

PMID- 16972167
TI  - Do benzodiazepines mimic reverse-turn structures?
AB  - The role of benzodiazepine derivatives (BZD) as a privileged scaffold that mimics
      beta-turn structures (Ripka et al. (1993) Tetrahedron 49:3593-3608) in
      peptide/protein recognition was reexamined in detail. Stable BZD ring conformers
      were determined with MM3, and experimental reverse-turn structures were extracted
      from the basis set of protein crystal structures previously defined by Ripka et
      al. Ideal beta-turns were also modeled and similarly compared with BZD
      conformers. Huge numbers of conformers were generated by systematically scanning
      the torsional degrees of freedom for BZDs, as well as those of ideal beta-turns
      for comparison. Using these structures, conformers of BZDs were fit to
      experimental structures as suggested by Ripka et al., or modeled classical beta
      turn conformers, and the root-mean-square deviation (RMSD) values were calculated
      for each pairwise comparison. Pairs of conformers with the smallest RMSD values
      for overlap of the four alpha-beta side-chain orientations were selected. All
      overlaps of BZD conformers with experimental beta-turns yielded one or more
      comparisons where the least RMSD was significantly small, 0.48-0.86 angstroms, as
      previously suggested. Utilizing a different methodology, the overall conclusion
      that benzodiazepines could serve as reverse-turn mimetics of Ripka et al. is
      justified. The least RMSD values for the overlap of BZDs and modeled classical
      beta-turns were also less than 1 angstrom. When comparing BZDs with experimental
      or classical beta-turns, the set of experimental beta-turns selected by Ripka et
      al. fit the BZD scaffolds better than modeled classical beta-turns; however, all
      the experimental beta-turns did not fit a particular BZD scaffold better. A
      single BZD ring conformation, and/or chiral orientation, can mimic some, but not
      all, of the experimental beta-turn structures. BZD has two central ring
      conformations and one chiral center that explains why the four variations of the
      BZD scaffold can mimic all types of beta-turn structure examined. It was found,
      moreover, that the BZD scaffold also mimics each of the nine clusters of
      experimental orientations of side chains of reverse turns in the Protein Data
      Bank, when the new classification scheme for the four side-chain directions (the
      relative orientations of alpha-beta vectors of residues i through i+3) was
      considered (Tran et al. (2005) J Comput-Aided Mol Des 19:551-566).

PMID- 16972168
TI  - Three dimensional model of severe acute respiratory syndrome coronavirus helicase
      ATPase catalytic domain and molecular design of severe acute respiratory syndrome
      coronavirus helicase inhibitors.
AB  - The modeling of the severe acute respiratory syndrome coronavirus helicase ATPase
      catalytic domain was performed using the protein structure prediction Meta Server
      and the 3D Jury method for model selection, which resulted in the identification
      of 1JPR, 1UAA and 1W36 PDB structures as suitable templates for creating a full
      atom 3D model. This model was further utilized to design small molecules that are
      expected to block an ATPase catalytic pocket thus inhibit the enzymatic activity.
      Binding sites for various functional groups were identified in a series of
      molecular dynamics calculation. Their positions in the catalytic pocket were used
      as constraints in the Cambridge structural database search for molecules having
      the pharmacophores that interacted most strongly with the enzyme in a desired
      position. The subsequent MD simulations followed by calculations of binding
      energies of the designed molecules were compared to ATP identifying the most
      successful candidates, for likely inhibitors - molecules possessing two
      phosphonic acid moieties at distal ends of the molecule.

PMID- 16972169
TI  - Ab initio computational modeling of long loops in G-protein coupled receptors.
AB  - A newly developed approach for predicting the structure of segments that connect
      known elements of secondary structure in proteins has been applied to some of the
      longer loops in the G-protein coupled receptors (GPCRs) rhodopsin and the
      dopamine receptor D2R. The algorithm uses Monte Carlo (MC) simulation in a
      temperature annealing protocol combined with a scaled collective variables (SCV)
      technique to search conformation space for loop structures that could belong to
      the native ensemble. Except for rhodopsin, structural information is only
      available for the transmembrane helices (TMHs), and therefore the usual approach
      of finding a single conformation of lowest energy has to be abandoned. Instead
      the MC search aims to find the ensemble located at the absolute minimum free
      energy, i.e., the native ensemble. It is assumed that structures in the native
      ensemble can be found by an MC search starting from any conformation in the
      native funnel. The hypothesis is that native structures are trapped in this part
      of conformational space because of the high-energy barriers that surround the
      native funnel. In this work it is shown that the crystal structure of the second
      extracellular loop (e2) of rhodopsin is a member of this loop's native ensemble.
      In contrast, the crystal structure of the third intracellular loop is quite
      different in the different crystal structures that have been reported. Our
      calculations indicate, that of three crystal structures examined, two show
      features characteristic of native ensembles while the other one does not. Finally
      the protocol is used to calculate the structure of the e2 loop in D2R. Here, the
      crystal structure is not known, but it is shown that several side chains that are
      involved in interaction with a class of substituted benzamides assume
      conformations that point into the active site. Thus, they are poised to interact
      with the incoming ligand.

PMID- 16972170
TI  - Pharmacophore model for bile acids recognition by the FPR receptor.
AB  - Formyl-peptide receptors (FPRs) belong to the family A of the G-protein coupled
      receptor superfamily and include three subtypes: FPR, FPR-like-1 and FPR-like-2.
      They have been involved in the control of many inflammatory processes promoting
      the recruitment and infiltration of leukocytes in regions of inflammation through
      the molecular recognition of chemotactic factors. A large number of structurally
      diverse chemotypes modulate the activity of FPRs. Newly identified antagonists
      include bile acids deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA). The
      molecular recognition of these compounds at FPR receptor was computationally
      investigated using both ligand- and structure-based approaches. Our findings
      suggest that all antagonists bind at the first third of the seven helical
      bundles. A closer inspection of bile acid interaction reveals a number of
      unexploited anchor points in the binding site that may be used to aid the design
      of new potent and selective bile acids derivatives at FPR.

PMID- 16972171
TI  - Prolonged moderate-intensity exercise without and with L-carnitine
      supplementation in patients with MCAD deficiency.
AB  - Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is probably the most
      common inborn error of fatty acid oxidation (FAO). Routine L-carnitine
      supplementation in the treatment of MCADD is controversial. To establish the
      effects of L-carnitine supplementation during prolonged moderate-intensity
      exercise in MCADD, five patients and three control subjects were studied during 2
      hours of moderate-intensity exercise after a 12-hour fast. Patients were studied
      twice, once with and once without L-carnitine supplementation (50 mg/kg per day).
      Blood samples were collected before, during and after exercise, and analysed for
      routine parameters, acylcarnitines and carnitine biosynthesis intermediates.
      Urine was collected before and after exercise, and analysed for acylcarnitines.
      All patients were able to complete the exercise test without any apparent
      clinical or biochemical adverse effects, even without L-carnitine
      supplementation. A significant rise in plasma free fatty acids and
      octanoylcarnitine levels during exercise was seen in all patients, indicating a
      substantial increase in FAO during exercise. Octanoylcarnitine levels in plasma
      were significantly higher in patients with L-carnitine supplementation,
      suggesting increased clearance of accumulating acylcarnitines. A statistically
      significant increase of plasma and urinary free carnitine levels, as well as of
      plasma gamma-butyrobetaine was seen in MCADD patients without L-carnitine
      supplementation. These data suggest an increase in carnitine biosynthesis. In
      conclusion, although L-carnitine supplementation may promote clearance of
      accumulating acylcarnitines during moderate-intensity exercise, no apparent
      beneficial effect of this supplementation on clinical and biochemical parameters
      was observed in MCADD patients. Our results suggest that MCADD patients are able
      to increase carnitine biosynthesis during exercise to compensate for carnitine
      losses.

PMID- 16972172
TI  - Critical assessment of chitotriosidase analysis in the rational laboratory
      diagnosis of children with Gaucher disease and Niemann-Pick disease type A/B and
      C.
AB  - Laboratory diagnosis of lysosomal storage disorders, especially sphingomyelinase
      deficiency (Niemann-Pick disease type A/B) and Niemann-Pick disease type C (NPC)
      can be challenging. We therefore aimed to analyse the feasibility of first-step
      screening with specific chitotriosidase cut-off values in children </= 10 years
      of age with visceral organomegaly (hepatomegaly, splenomegaly, or
      hepatosplenomegaly) in whom a storage disorder was suspected. We conducted a
      retrospective, cross-sectional, referral, single-centre study to assess
      diagnostic test properties in 106 individuals. Median chitotriosidase activity
      was 12 655 nmol/h per ml (interquartile range 4693-20982) in Gaucher disease
      (GD); 780 (465-1298) in SMD (sphingomyelinase deficiency); 925 (319-1215) in NPC
      and 50 (29-54) in patients with miscellaneous diseases. To restrict the
      differential diagnosis to GD, SMD or NPC, chitotriosidase activity above 200
      nmol/h per ml had a sensitivity of 96%, specificity of 100%, positive predictive
      value (PPV) of 100%, and negative predictive value (NPV) of 95%. For GD alone,
      chitotriosidase activity above 4000 nmol/h per ml had a sensitivity of 77%,
      specificity of 100%, PPV of 100% and NPV of 92%. Of the 44 patients analysed,
      4.5% were homozygous and 36.4% heterozygous for chitotriosidase gene duplication.
      Adjusting for the chitotriosidase genotype, chitotriosidase activities were
      higher in GD type III than in GD type I. We conclude that, in the above setting,
      the degree of elevation of chitotriosidase activity can be applied to increase
      the likelihood of GD, SMD, or NPC and guide the choice of the appropriate
      confirmatory assay.

PMID- 16972174
TI  - Needs assessment and review of services for people with inherited metabolic
      disease in the United Kingdom.
AB  - Patients with inherited metabolic diseases need to be viewed as a specialist care
      group because of the range of expertise required for their diagnosis and
      management. In the UK, professional concerns have been expressed that existing
      services would struggle to meet needs resulting from new diagnostic and screening
      techniques, new treatments and increased survival. This needs assessment and
      service review was therefore undertaken at the request of the Joint Committee on
      Medical Genetics, guided by a national multidisciplinary stakeholder group. All
      24 specialist centres identified in the UK provided evidence for the review.
      Approximately 10 000 patients are known to services and their annual number of
      referrals is increasing. Possible shortfalls in the number of patients attending
      specialist services were estimated for the UK as a whole by extrapolating the
      results from the region with the most comprehensive service and comparing this
      with known patient numbers. This analysis suggests that a further 5600 children
      and 3300 adults are not looked after by specialist services or have been lost to
      follow-up. The comprehensiveness of services was assessed using a new scoring
      system for clinical and organizational criteria. There are major regional
      disparities in the comprehensiveness of service provision across the country,
      with some regions having little or no specialist service. Unmet need will
      increase as a result of new diagnostic technologies, more effective treatments
      and new neonatal screening programmes; specialist services need to be developed
      and expanded to provide a comprehensive and more equitable service to the UK
      population.

PMID- 16972173
TI  - Improvement of sympathetic skin responses under enzyme replacement therapy in
      Fabry disease.
AB  - AIM: To report the effect of enzyme replacement therapy (ERT) in sympathetic skin
      responses (SSR) of patients with Fabry disease. PATIENTS AND METHODS: Seven male
      patients were included in an open-label protocol using agalsidase-alfa, continued
      at regular intervals. Five patients completed 24 months of ERT and two of them
      completed 18 months. Two main measurements were performed at baseline, as well as
      1 and 2 years after ERT: (1) a standard neurological examination (NE), with a
      detailed evaluation of the sensory perception of light touch, pinprick, cold,
      hot, and vibratory stimuli; (2) the SSR amplitudes. RESULTS: Although there were
      no significant differences between NE in this time period, all patients reported
      general improvement in their subjective reports of acroparaesthesia and sweating.
      Before starting ERT, the SSR amplitudes were either too small (3/7 patients) or
      absent (4/7 patients): the average (range) amplitude of 122 microV (0 through
      492) was statistically smaller than that found in a control group, i.e. 1453.6
      microV (619.7-2754) (p<0.0001, t-test). Mean +/- SD SSR amplitude increased to
      1088+/- 690 microV in the second year of ERT, reaching the range found in a
      normal control group (p=0.004). CONCLUSION: ERT improved SSR continuously in
      Fabry patients in 2 years of observation. Although the mechanism of the SSR
      improvement is unknown, this response to ERT can be clinically significant if it
      reflects a normalization in sweating.

PMID- 16972175
TI  - Fumaric aciduria: mild phenotype in a 8-year-old girl with novel mutations.
AB  - Fumaric aciduria is a rare, autosomal recessive disorder caused by deficient
      activity of fumarate hydratase (FH). Common clinical features are hypotonia,
      failure to thrive, severe psychomotor retardation and seizures. Facial
      dysmorphism and brain malformations are frequent. Recently, some FH gene
      mutations have been associated with inherited cutaneous and uterine leiomyomas
      and papillary renal cell cancer. Our patient had a relatively mild phenotype, a
      previously not reported genotype and familial tumour predisposition. The mother
      and grandmother had uterine myomas. The paternal grandfather and his two brothers
      died from lung and laryngeal cancers. The pregnancy was complicated by bleeding
      and intrauterine growth retardation. Delivery was after 35 weeks, with normal
      Apgar score. The girl was hypotonic since birth. At age 2 months the parents
      noticed short apnoeic crises. She could sit at age 1.5 years, and walk with
      assistance at 4 years. At age 8 years highly increased excretion of fumaric acid
      was found twice (217 and 445 mmol/mol creatinine). Shortly before that the girl
      started to have leg and arm spasms. Grand mal seizures occurred twice. Facial
      dysmorphism included depressed nasal bridge, anteverted ears, hypertelorism and
      microcephaly. Speech was limited to few disyllables. She was atactic with spastic
      paraparesis. Brain MRI showed slight ventriculomegaly, white-matter atrophy and
      hypoplasia of corpus callosum. Activity of FH in fibroblasts was 1.9 nmol/min/mg
      protein (controls 40-80). Analysis of the FH gene revealed the maternally derived
      c.1029_1031delAGT mutation, resulting in Val deletion and substitution of Gln by
      His, and paternally derived c.976C > T mutation, resulting in substitution of Pro
      by Ser.

PMID- 16972176
TI  - LAT1 gene variants--potential factors influencing the clinical course of
      phenylketonuria.
AB  - The LAT1 amino acid exchanger is responsible for phenylalanine transport across
      the blood-brain barrier. As phenylalanine excess in the brain leads to mental
      retardation in untreated patients with phenylketonuria, mutations of the LAT1
      gene can be responsible for milder clinical manifestations (lower brain toxicity
      of hyperphenylalaninaemia) observed in some patients. The aim of this study was
      to screen for LAT1 gene mutations in phenylketonuric patients. Within the coding
      sequence of the gene, three polymorphism and one new mutation (G41D) were
      detected. The protein sequence change due to the mutation described could
      influence the clinical course of phenylketonuria.

PMID- 16972177
TI  - Lipoprotein lipase gene analyses in one Turkish family and three different
      Chinese families with severe hypertriglyceridaemia: one novel and several
      established mutations.
AB  - Lipoprotein lipase (LPL, triacylglycerol acylhydrolase; EC 3.1.1.3) deficiency
      (OMIM 238600) is an autosomal recessive inherited condition caused by mutations
      in the LPL gene, either in a homozygous or in a compound heterozygous state,
      leading to loss of lipolytic activity and resulting in severe
      hypertriglyceridaemia and subsequent risk for developing pancreatitis. Numerous
      LPL gene mutations leading to loss of catalytic function have been described. In
      this present study, we describe full clinical, biochemical and molecular analyses
      of severe hypertriglyceridaemic individuals in one Turkish and three Chinese
      families. We established one novel mutation (delCT1312-1313), a new combination
      of mutations (S193R and I194T) and four previously reported mutations (L252R,
      L252V, S193R and I194T) of the LPL gene and report phenotypes for these and four
      previously described mutations. Finally, we show that two patients homozygous for
      the LPL gene delCT1312-1313 mutations are characterized by absence of LPL
      activity that coincides with absence of LPL protein.

PMID- 16972178
TI  - Portal hypertension in a patient with Hunter disease.
AB  - Hepatosplenomegaly is one of the cardinal signs of Hunter disease; however,
      portal hypertension has not been described. We report portal hypertension in an
      adult Hunter patient with the attenuated phenotype.

PMID- 16972179
TI  - Successful treatment of pyridoxine-unresponsive homocystinuria with betaine in
      pregnancy.

PMID- 16972180
TI  - Gerard M. Guiraudon: a pioneer in surgery for tachycardias.

PMID- 16972181
TI  - Development of synthetic food-related attractant for Carpophilus davidsoni and
      its effectiveness in the stone fruit orchards in southern Australia.
AB  - An effective synthetic attractant, based on host-related volatile compounds, was
      developed for the nitidulid beetle, Carpophilus davidsoni, as part of a program
      for managing this pest in Australian peach orchards. Fermenting peach juice and
      whole peaches and nectarines served as chemical models for the attractant, and
      synthetic formulations were sought that matched the natural sources, both with
      respect to emission rates of key chemicals (in ng/min) and attractiveness to
      flying beetles. All volatile sources were kept in airstreams during laboratory
      chemical measurements, and these airstreams were subsequently directed to the
      wind-tunnel behavioral assay, allowing the determined emission rates of compounds
      to be associated with particular levels of attractiveness. Chemical sampling of
      airstreams was by solid-phase microextraction, and analysis was by gas
      chromatography and mass spectrometry. A volatile delivery system was coupled to
      the wind tunnel and allowed facile manipulation of natural and synthetic scents.
      The final blend, modeled after fermenting peach juice, contained ethanol as the
      main constituent and 2-methyl-1-propanol, 2-methyl-1-butanol, 3-methyl-1-butanol,
      acetaldehyde, and ethyl acetate as minor constituents, all in water solution.
      Blend components were synergistic, and use of a mixture was essential for optimal
      attractiveness. The synthetic blend was highly effective in the field and is
      intended to replace fermenting peach juice and overripe peaches, which were
      previously used as synergists of the Carpophilus spp. aggregation pheromones in
      attract-and-kill stations.

PMID- 16972182
TI  - Understanding the relationship between mental disorder and violence: the need for
      a criminological perspective.
AB  - This paper offers a criminologically informed framework to guide research on the
      relationship between mental disorder and violence. Criminological theories
      examined include social learning, social stress, social control, rational choice,
      and social disorganization. In addition, the "criminal careers" and "local life
      circumstance" methodologies are reviewed. It is argued that adopting a
      criminologically informed framework that takes into account within-person changes
      over time will contribute greatly to our understanding of the factors that affect
      violence among people with mental disorder living in the community, and enhance
      the capacity of research to support effective evidenced-based case management
      programs aimed at reducing violence.

PMID- 16972184
TI  - Real-time imaging and quantification of brain delivery of liposomes.
AB  - The surgical delivery of therapeutic agents into the parenchyma of the brain is
      problematic because it has been virtually impossible to know with any certainty
      where infused material is going, and how much to infuse. We have started to use
      liposomes loaded with Gadoteridol (GDL) as a tracer that allows us to follow
      infusions in real-time on magnetic resonance imaging (MRI). MRI allows precise
      tracking and measurement of liposomes loaded with markers and therapeutics. This
      review provides an overview of real-time delivery of liposomes to the central
      nervous system (CNS), and discusses the technical aspects of delivery, liposomes
      as colloidal systems of delivery, real-time distribution of liposomes in CNS, and
      quantification of liposome distribution. Our data suggests that real-time
      monitoring of liposomal drug infusion is likely to improve outcomes of clinical
      trials where convection-enhanced delivery (CED) is being used to target drugs to
      specific brain structures through limitation of systemic toxicity and reduction
      of side effects. This review is a summary of work done by our group over the past
      four years.

PMID- 16972183
TI  - Protection against chemotherapy-induced alopecia.
AB  - PURPOSE: The goal is to provide an overview on the advances in protection against
      chemotherapy-induced alopecia (CIA). MATERIALS AND METHODS: The four major parts
      of this review are (a) overview of the hair follicle biology, (b) characteristics
      of CIA, (c) state-of-the-art animal models of CIA, and (d) experimental
      approaches on protection against CIA. RESULTS: The hair follicle represents an
      unintended target of cancer chemotherapy. CIA is a significant side effect that
      compromises the quality of life of patients. Overcoming CIA represents an area of
      unmet needs, especially for females and children. Significant progresses have
      been made in the last decade on the pathobiology of CIA. The pharmacological
      agents under evaluation include drug-specific antibodies, hair growth cycle
      modifiers, cytokines and growth factors, antioxidants, cell cycle or
      proliferation modifiers, and inhibitors of apoptosis. Their potential
      applications and limitations are discussed. CONCLUSION: Multiple classes of
      agents with different action mechanisms have been evaluated in animal CIA models.
      Most of these protective agents have activity limited to a single
      chemotherapeutic agent. In comparison, calcitriol and cyclosporine A have broader
      spectrum of activity and can prevent against CIA by multiple chemotherapeutic
      agents. Among the three agents that have been evaluated in humans, AS101 and
      Minoxidil were able to reduce the severity or shorten the duration of CIA but
      could not prevent CIA.

PMID- 16972185
TI  - Agglomerate strength and dispersion of salmeterol xinafoate from powder mixtures
      for inhalation.
AB  - PURPOSE: The study investigated the role of agglomeration and the effect of fine
      lactose size on the dispersion of salmeterol xinafoate (SX) from SX-lactose
      mixtures for inhalation. METHODS: Particle size distributions were characterised
      by Malvern Mastersizer S, Aerosizer and Spraytec, and imaging conducted by
      scanning electron microscopy (SEM). Inter-particulate adhesion was quantified by
      atomic force microscopy. Deposition of SX was measured using a twin stage
      impinger. SX was analysed using validated high-performance liquid chromatography
      method (r(2)=1.0, CV=0.4-1.0%). RESULTS: Addition of fine lactose with a volume
      median diameter (VMD) of 7.9 microm to a SX-lactose carrier and carrier-free
      mixture resulted in significantly better dispersion (16.8% for 20% added fine
      lactose) than fractions with VMD of 3.0, 17.7 and 33.3 microm (less than 9.1% for
      20% fine lactose). Using the carrier-free mixtures, particle sizing of the
      aerosol cloud using the Spraytec, coupled with the application of the Aerosizer
      using differing dispersion energies and SEMs of the samples, indicated that an
      open packed, agglomerate structure improved SX dispersion. The highest extent of
      SX dispersion occurred when SX and fine lactose were detached from the surface,
      usually in the form of loose agglomerates. CONCLUSIONS: The outcomes of this
      research demonstrated how agglomerate structure influenced dispersion and the key
      role of fine lactose particle size in SX dispersion from mixtures for inhalation.

PMID- 16972187
TI  - Local recurrence and distant metastasis of supratentorial primitive neuro
      ectodermal tumor in an adult patient successfully treated with intensive
      induction chemotherapy and maintenance temozolomide.
AB  - Supratentorial primitive neuro-ectodermal tumors (PNET) in adults are very rare.
      Extraneural metastasis are unusual and the optimal palliative chemotherapy
      regimen is not established. We present a 26-year-old patient with local
      recurrence and distant metastasis of supratentorial PNET successfully treated
      with intensive induction chemotherapy and maintenance temozolomide.

PMID- 16972188
TI  - Neuroradiographic variant of posterior reversible leukoencephalopathy.

PMID- 16972186
TI  - Anorexia nervosa and osteoporosis.
AB  - Anorexia nervosa (AN), a condition of severe undernutrition, is associated with
      low bone mineral density (BMD) in adults and adolescents. Whereas adult women
      with AN have an uncoupling of bone turnover markers with increased bone
      resorption and decreased bone formation markers, adolescents with AN have
      decreased bone turnover overall. Possible contributors to low BMD in AN include
      hypoestrogenism and hypoandrogenism, undernutrition with decreased lean body
      mass, and hypercortisolemia. IGF-I, a known bone trophic factor, is reduced
      despite elevated growth hormone (GH) levels, leading to an acquired GH resistant
      state. Elevated ghrelin and peptide YY levels may also contribute to impaired
      bone metabolism. Weight recovery is associated with recovery of BMD but this is
      often partial, and long-term and sustained weight recovery may be necessary
      before significant improvements are observed. Anti-resorptive therapies have been
      studied in AN with conflicting results. Oral estrogen does not increase BMD or
      prevent bone loss in AN. The combination of bone anabolic and anti-resorptive
      therapy (rhIGF-I with oral estrogen), however, did result in a significant
      increase in BMD in a study of adult women with AN. A better understanding of the
      pathophysiology of low BMD in AN, and development of effective therapeutic
      strategies is critical. This is particularly so for adolescents, who are in the
      process of accruing peak bone mass, and in whom a failure to attain peak bone
      mass may occur in AN in addition to loss of established bone.

PMID- 16972190
TI  - Longitudinal assessment of parental satisfaction with children's psychiatric
      hospitalization.
AB  - OBJECTIVE: To examine trends over time in parents' satisfaction with their
      children's prior psychiatric hospitalization and whether such trends are related
      to postdischarge outcomes. STUDY DESIGN/DATA COLLECTION: Parents of 107 child
      inpatients completed a satisfaction survey at discharge. Satisfaction with the
      same inpatient stay was re-assessed 3, 6, and 12 months after discharge. Parents
      also provided ratings of behavioral symptoms at admission, discharge, and at
      postdischarge follow-ups. PRINCIPAL FINDINGS: Random regression analyses
      indicated significant decline in satisfaction from discharge to follow-up. The
      proportion of parents reporting that they were not satisfied doubled between
      discharge and 3-month follow-up. Parents whose satisfaction appraisals shifted
      from satisfied at discharge to not satisfied at follow-up also provided mean
      ratings of their child's disruptive behavioral problems at follow-up that were
      higher than those of parents who reported satisfaction with inpatient care at
      both times. CONCLUSIONS: Findings suggest that appraisals of inpatient care are
      subject to change, and may become more negative when clinical improvement
      associated with hospitalization dissipates in the months following discharge.

PMID- 16972189
TI  - Interventions to address the academic impairment of children and adolescents with
      ADHD.
AB  - There exists a strong link between ADHD and academic underachievement. Both the
      core behavioral symptoms of ADHD and associated executive functioning deficits
      likely contribute to academic impairment. Current evidence-based approaches to
      the treatment of ADHD (i.e., stimulant medication, clinical behavior therapy and
      classroom behavioral interventions) have demonstrated a robust impact on
      behavioral variables such as attention and disruptive behavior within classroom
      analogue settings; however, their efficacy in improving academic outcomes is much
      less clear. Although surprisingly few treatment outcome studies of ADHD have
      attempted to incorporate interventions that specifically target academic
      outcomes, the studies that are available suggest that these interventions may be
      beneficial. The state of the treatment literature for addressing academic
      impairment in children and adolescents with ADHD will be reviewed herein, as well
      as limitations of current research, and directions for future research.

PMID- 16972191
TI  - Perceived physical maturity, age of romantic partner, and adolescent risk
      behavior.
AB  - Early pubertal timing and advanced physical maturity for age confer elevated risk
      for problem behaviors for both boys and girls. However, examinations of possible
      biological and social mediators have been limited. Using more than 4,000
      adolescents under age 15 who participated in Waves I and II of the National
      Longitudinal Study of Adolescent Health (Add Health), we examined the
      relationship between perceived physical maturity and membership in risk behavior
      clusters, and tested whether having a romantic partner mediates the maturity/risk
      behavior relationship. Results of multinomial regression models indicated that
      for both boys and girls, advanced physical maturity was associated with
      membership in higher risk clusters, and that having a romantic partner plays an
      important mediating role in this association. For females, the additional impact
      of having an older partner, versus any partner at all, was substantial and
      particularly important for the highest risk clusters. The role of partner age
      could not be tested for males. Because romantic partners elevate risk for young
      adolescent males and females, there is a need to identify and understand facets
      and developmental functions of adolescent romantic relationships that play a role
      in substance use and sexual decisions.

PMID- 16972192
TI  - Personality traits in Sardinia: testing founder population effects on trait means
      and variances.
AB  - Potential founder population effects on personality trait means and variances
      were examined in a large, genetically homogeneous sample (N=5,669) from the
      Ogliastra, an isolated region within Sardinia, Italy. The Italian version of the
      Revised NEO Personality Inventory showed good psychometric properties: Internal
      consistency reliabilities ranged from 0.80 to 0.87; the factor structure
      replicated the American normative structure; and associations with education and
      gender replicated cross-cultural patterns. The hypothesis that mean trait levels
      in the Sardinian founder population would differ from mainland Italian values was
      not supported. Phenotypic variation in this founder population was within the
      range found in other cultures. However, the hypothesis of restricted phenotypic
      variation was supported for all five factors and 28 of the 30 facets when a
      Sardinian subsample matched on age, sex, and education was compared to a mainland
      Italian sample. The genetic homogeneity effect on the phenotypic expression of
      complex traits merits further exploration.

PMID- 16972193
TI  - Spreadsheets, service providers, and the Statehouse: using data and the
      wraparound process to reform systems for children and families.
AB  - Evaluation descriptions in the research literature tend to ignore the full
      context of the community change efforts from which they emerged. In this paper,
      we describe a range of evaluation studies and data collection activities
      conducted over the course of one state's effort to reform its child welfare
      system on behalf of families with children experiencing serious mental health
      problems. Initial activities included studies of the prevalence of unmet mental
      health need in children and youth in the state. As these needs were addressed,
      evaluation activities examined the impact of a pilot wraparound program that
      became a major part of systems reform. Later efforts included implementation
      analysis of wraparound programs and assessment of priorities for continued
      systems reform. As we describe this set of evaluation activities, we discuss how
      data collection evolved to meet the needs of stakeholders over time and consider
      lessons learned about the roles of research and information sharing in shaping
      community change efforts.

PMID- 16972197
TI  - Dependence of synergistic fungicidal activity of Cu2+ and allicin, an allyl
      sulfur compound from garlic, on selective accumulation of the ion in the plasma
      membrane fraction via allicin-mediated phospholipid peroxidation.
AB  - Allicin was effective in decreasing the lethal concentration of Cu (2+) against
      various fungal strains including a plant pathogen, Fusarium oxysporum, so that
      the minimum fungicidal concentration (MFC) of the ion for the fungus could be
      reduced to 2 % of that detected without allicin. In Saccharomyces cerevisiae, Cu
      (2+) was not apparently taken up by cells when added alone at a non-lethal
      concentration, whereas the ion was efficiently incorporated into cells in the
      presence of allicin, as in the case of cells treated with the ion at a lethal
      concentration. Although allicin likely increased cellular permeability to Cu (2+)
      due to its promotive effect on plasma membrane phospholipid peroxidation, these
      cell-surface events did not result in endogenous reactive oxygen species (ROS)
      production, a typical toxic effect of the ion. Cu (2+) was detected in the
      cytoplasmic fraction of cells that had been treated with the ion at a lethal
      concentration, whereas the ion was entrapped in the plasma membrane fraction upon
      their treatment with the ion at a low concentration in combination with allicin.
      Cu (2+) could be solubilized from the plasma membrane fraction by a procedure for
      the extraction of hydrophobic proteins rather than the extraction of
      phospholipids, suggesting its complexation with a plasma membrane protein as a
      result of allicin treatment. Such a subcellular localization of Cu (2+) resulted
      in the selective leakage of intracellular K (+), but not in the disruptive damage
      on the plasma membrane, and was considered to underlie the synergistic fungicidal
      activity of Cu (2+) and allicin.

PMID- 16972194
TI  - Illness representations, self-regulation, and genetic counseling: a theoretical
      review.
AB  - In this article the Self Regulatory Theory (Leventhal, 1970; Leventhan H.,
      Benyamini, Brownlee, Diefenbach, Leventhal E.A., Patrick-Miller, & Robitaille,
      1997) is presented as a framework for conceptualizing genetic counseling.
      Findings published in the genetic counseling literature are re-interpreted from
      the perspective of the theory. Clients are seen as active information processors
      rather than passive receivers of information. Research related to clients'
      representations of genetic causality of disease and specific genetic conditions
      is reviewed. Associations of genetic illness representations to self
      representations, coping and health behaviors are examined, and suggestions are
      made for applications of the theory in research and clinical practice.

PMID- 16972198
TI  - The leaf volatile constituents of Isatis tinctoria by Solid-Phase Microextraction
      and Gas chromatography/Mass Spectrometry.
AB  - The leaf volatile constituents of Isatis tinctoria L. (Brassicaceae) have been
      studied by Solid-Phase Microextraction and Gas chromatography/Mass Spectrometry
      (SPME/GC-MS). Seventy components were fully characterized by mass spectra, linear
      retention indices, and injection of standards; the average composition (ppm) as
      single components and classes of substances is reported. Aliphatic hydrocarbons,
      acids, alcohols, aldehydes and esters, aromatic aldehydes, esters and ethers,
      furans, isothiocyanates and thiocyanates, sulfurated compounds, nitriles,
      terpenes and sesquiterpenes were identified. Leaf volatiles in Isatis tinctoria
      L. were characterized by a high amount of isothiocyanates which accounted for
      about 40 % of the total volatile fraction. Isothiocyanates are important and
      characteristic flavour compounds in Brassica vegetables and the cancer chemo
      protective attributes are recently responsible for their growing interest.

PMID- 16972199
TI  - Solar simulator-induced phototoxicity of the furoquinoline alkaloid dictamnine
      compared to 8-methoxypsoralen and 5-methoxypsoralen.
AB  - Dictamnine, a furoquinoline alkaloid of the Rutaceae plant family, has been shown
      to be mutagenic and phototoxic in bacteria and yeasts. Here, we have investigated
      the phototoxic effect of dictamnine in human Jurkat T cells and HaCaT
      keratinocytes. Dictamnine was isolated from the roots of DICTAMNUS ALBA L. and
      was photoactivated with solar simulated radiation, delivered from a 1000-W xenon
      arc lamp with a maximal output between 300 - 800 nm. Dictamnine displayed
      concentration- and light-dependent phototoxic effects in both cell lines. In
      comparison to the structurally related furocoumarins 5-methoxypsoralen and 8
      methoxypsoralen, dictamnine was less phototoxic. Nevertheless, it may play a
      major role in the elicitation of phytophotodermatitis because of its abundance in
      plants of the Rutaceae family.

PMID- 16972200
TI  - Activity of quinones from teak (Tectona grandis) on fungal cell wall stress.
AB  - Teak ( Tectona grandis L.f., Verbenaceae) sawdust extract inhibited the growth of
      Aspergillus niger. Centrifugal partition chromatography was used to isolate the
      active compounds. By (1)H-NMR the active compounds were identified as
      deoxylapachol and tectoquinone. Two A. niger transgenic strains which show
      induction of 1,3 -alpha-D-glucan synthase were used as a cell wall damage model.
      The result showed that deoxylapachol from T. grandis extract induced fungal cell
      wall stress.

PMID- 16972201
TI  - Inhibition of protein tyrosine phosphatase 1B by prenylated isoflavonoids
      isolated from the stem bark of Erythrina addisoniae.
AB  - It has been suggested that protein tyrosine phosphatase 1B (PTP1B) inhibitors
      might be a therapeutic target for the treatment of type 2 diabetes and obesity. A
      bioassay-guided phytochemical study of the EtOAc extract of the stem bark of
      Erythrina addisoniae (Leguminosae) resulted in the identification of a new PTP1B
      inhibitory compound, 5,2',4'-trihydroxy-6-(gamma,gamma-dimethylallyl)-2''',2'''
      dimethyldihydropyrano[5''',6''']isoflavanone ( 6), along with five known
      prenylated isoflavonoids, orientanol E ( 1), senegalensin ( 2), warangalone ( 3),
      warangalone 4'-methyl ether ( 4) and 2,3-dihydroauriculatin ( 5). Compounds 1, 5
      and 6 inhibited PTP1B with IC (50) values ranging from 2.6 +/- 0.5 to 10.1 +/-
      0.3 microM. Our results indicate that hydroxylation at both 2'- and 4'-positions
      in the B-ring and cyclization between a hydroxy group at C-7 and one of the
      prenyl groups at C-6 or C-8 in the A-ring may be important for activity. Thus,
      compounds 5 and 6 could be a new class of natural PTP1B inhibitors.

PMID- 16972202
TI  - Two new phenolic glycosides from the barks of Hydnocarpus annamensis and their
      anti-inflammatory and anti-oxidation activities.
AB  - Two new phenolic glycosides 1 and 2 were isolated from the barks of Hydnocarpus
      annamensis, along with eighteen known compounds. The structures of all compounds
      were deduced using spectroscopic methods. Anti-inflammatory and anti-oxidation
      activities were evaluated. Among the isolates, compounds 1, 5, 15 and 17
      exhibited COX-2 inhibitory activities, with an inhibitory rate of 60.3 - 63.4 %
      at 10 microM. Compounds 7, 12, 13 and 20 showed anti-oxidation capacities in the
      DPPH free-radical assay, with a scavenging effect of 60.9 - 69.4 % at 50 microM,
      and 18.5 - 34.6 % at 10 microM.

PMID- 16972203
TI  - [Spinal regional anesthetic approaches in children: caudal block and spinal
      anesthesia].
AB  - Caudal anesthesia is a safe, simple and very effective method to provide
      excellent perioperative analgesia. It is used routineously in pediatric
      anesthesia and can be applied to nearly all children with surgery below the
      umbilicus. In contrast, spinal anesthesia is a very special technique for former
      preterm infants below the 50th postconceptive week who are prone to develop
      postoperative apnea. It has been suggested that some of the problems associated
      with general anesthesia in these patients may be avoided by the use of spinal
      anesthesia.

PMID- 16972204
TI  - [Invasive cardiovascular monitoring--four methods compared].
AB  - The impact of invasive hemodynamic monitoring on patient safety and outcome in
      perioperative medicine remains inadequately tested and unproven. The indications
      for the use of these tools should, therefore, be evaluated according to an
      individual risk-benefit analysis. The measurement of central venous oxygen
      saturation (ScvO2) is of little invasiveness as most high-risk patients are
      instrumented with central venous catheters, and ScvO2 has been shown to improve
      outcome in patients with septic shock. Transpulmonary thermodilution (e.g. PiCCO
      system) delivers information not only on global cardiac function and
      intravascular volume status but also helps to define the pulmonary consequences
      of cardiovascular therapy. Transesophageal echocardiography (TEE) is a valuable
      tool in patients undergoing cardiac surgery and represents the beside-method of
      choice for rapid assessment of acute life-threatening cardiovascular instability.
      Apart from special indications, these tools tend to replace the pulmonary artery
      catheter (PAC) which has been shown to be of little value in various patient
      populations.

PMID- 16972205
TI  - [Out-of-hospital and early clinical management of polytrauma in a patient after
      severe car accident].
AB  - We report the case of a 30 year old driver of a car who was jammed after a severe
      traffic accident. In a step-by-step description of the out-of-hospital and early
      clinical management of the patient, the case report focuses on diagnostic,
      therapeutic, and strategic issues. Current controversies in the management of
      patients with combined thoracic and abdominal trauma are discussed in the light
      of recent literature.

PMID- 16972206
TI  - [Introduction--airway management: deciding on what to do or not to do].

PMID- 16972207
TI  - [Clinical management of the difficult airway].
AB  - Difficult airway management is among the key requirements in routine anaesthesia.
      Failures to secure the airways resulting in a "Cannot intubate, Cannot ventilate"
      situation can drastically increase morbidity and mortality of patients within a
      very short time. Therefore, an algorithm for management of the expected and
      unexpected difficult airway describing the sequence of various procedures,
      adapted to internal standards and to techniques that are available, has to be
      provided by each anaesthesia department. This not only facilitates the
      preparation of equipment and the training of personnel, but also ensures
      efficient decision making under time pressure.

PMID- 16972208
TI  - [Invasive airway management].
AB  - Invasive airway management techniques are the bottom line of most difficult
      airway management algorithms when less invasive measures (e.g. endotracheal
      intubation, bag-valve-mask ventilation, or supraglottic airways) have failed.
      Various devices for transtracheal jet ventilation in children are available,
      while cricothyrotomy is the gold standard for establishing an invasive airway in
      adults. Percutaneous tracheostomy could become an alternative to cricothyrotomy
      if applied by experienced physicians, however, clear scientific evidence to
      advocate percutaneous tracheostomy in airway emergencies is still pending.

PMID- 16972209
TI  - [Cardiac complications in patients with schizophrenic disorders].
AB  - It is well known, that patients with schizophrenia exhibit increased rates of
      cardiac morbidity and mortality. Frequent cardiovascular diseases are only
      partially explained by lifestyle, inactivity, dietary habits and nicotine abuse,
      but also by reduced compliance in prevention programs. On the other hand, it has
      been shown that particularly atypical antipsychotic agents are differentially
      responsible for high rates of obesity, hypertriglyceridemia, and diabetes.
      Therefore, a standardized evaluation of corresponding parameters is indicated in
      every patient. If needed, modulation of the medication regimen has to be
      performed. Additionally, a dietary counselling of the patient and his family
      should be offered. Besides pharmacological approaches to normalize dyslipidemia,
      specific behavioural therapy programmes are an option that may alter metabolic
      parameters. Threatening cardiac complications in long-term treatment of
      schizophrenia may also be the result of direct side effects under treatment with
      antipsychotics, like QT-prolongation triggering major arrhythmias. For
      prevention, predisposing risk factors like electrolyte disturbances, pre-existing
      cardiac diseases, co-medication with QT prolonging drugs and medication with
      potential cytochrome P450 interaction have to be taken into consideration.

PMID- 16972210
TI  - [Pharmacological treatment options in frontotemporal dementia].
AB  - In contrast to Alzheimer's disease, there are only few systematic trials for drug
      therapy of frontotemporal dementia (FTD). Neurochemically, a strong serotonergic
      deficit is supposed in FTD. This is the rationale for treatment, especially of
      behavioral abnormalities, with serotonergic antidepressants. However, only
      paroxetine and trazodone have been studied in trials with class I and II evidence
      so far. The results of paroxetine are inconsistent; and for trazodone a number of
      potential side-effects must be considered. Moreover, there is class II evidence
      for rivastigmine in FTD, even though a cholinergic deficit in this type of
      dementia is questionable. There are no published data from controlled trials for
      the use of memantine in FTD so far.

PMID- 16972211
TI  - [Initial symptoms, survival and causes of death in 115 patients with
      frontotemporal lobar degeneration].
AB  - The early and differential diagnosis of the clinical phenotypes of frontotemporal
      lobar degeneration (FTLD), including frontotemporal dementia (FTD), semantic
      dementia (SD) and non-fluent progressive aphasia (NFPA), can be challenging. It
      may be difficult not only to differentiate these conditions from normal aging,
      psychiatric disorders, and other dementias, but also to distinguish between them.
      For early diagnosis, information on the initial and presenting symptoms of the
      FTLD phenotypes is essential. In the present study caregivers of 78 patients with
      FTD, 20 patients with SD and 17 patients with PA were interviewed about initial
      symptoms. In patients with FTD, the most frequent initial symptoms were
      alterations of personality, followed by forgetfulness and word finding
      difficulty. Patients with SD presented with word finding difficulty and
      behavioral disturbances. Almost all patients with PA developed word finding
      difficulty as the first manifestation of their disorder. Diagnostic latency - the
      time from disease onset to diagnosis was 4.1 years in FTD, 4.2 years in SD and
      3.1 years in PA. Caregivers, and in some cases also patients, should be educated
      about the likely course and mortality of FTLD. To obtain information about
      survival time and cause of death associated with FTLD we analyzed follow-up data
      on 106 patients of whom 25 had died. The median survival time from the occurrence
      of first symptoms was 14 years. Mortality risk was significantly higher in
      patients with an early disease onset. Causes of death were varied, but pneumonia
      and sudden unexplained deaths were particularly frequent.

PMID- 16972212
TI  - [An expert system neurology--possibilities and limitations].
AB  - We present an expert system Neurology, which was developed completely on basis of
      the commercial available data base program Filemaker-7.0. At present it covers
      approximately 400 diagnoses of neurological and psychiatric diseases. After the
      input of cardinal symptoms, course and localisation of the disease the program
      calculates a first set of possible differential diagnoses and asks for additional
      symptoms or the performance of apparative diagnostics to investigate the final
      diagnose. At first, the performance of the expert system was tested with 15
      predetermined neurological case reports. Users with different previous knowledge
      of Neurology performed the input. In this test the program was able to identify
      the correct diagnose in nearly all cases and the diagnostic proposals were
      superior to those of the users with minor neurological training. In a second test
      with real patient data, the rate of correct diagnoses was approximately 80%. In
      summary, the used computer algorithms proved as appropriate for the aim of giving
      Neurological diagnoses. Possible additional applications could be student
      training or the use as interdisciplinary reference work.

PMID- 16972213
TI  - Clinical outcomes of neonatal hypoxic ischemic encephalopathy evaluated with
      diffusion-weighted magnetic resonance imaging.
AB  - PURPOSE: Detection of early phase neurological deficit in babies with hypoxic
      ischemic encephalopathy (HIE) is the most important step to determine the
      appropriate preventive treatment methods. Diffusion-weighted imaging (DWI) is the
      most sensitive radiological modality to detect ischemic changes in the brain, in
      their earliest phase. Herein, we present the results of our study about the role
      of DWI in the diagnosis and determining the prognosis of HIE in neonates.
      MATERIALS AND METHODS: The study included 36 cases (4 preterm, 32 term babies)
      who were diagnosed with HIE within 24 hours of birth and classified according to
      modified Sarnat staging. They were examined for the presence of neurological
      sequelae at 3 and 6 months of age with electroencephalography (EEG), visual
      evoked potential (VEP), brainstem auditory evoked potential (BAEP), and Denver II
      developmental screening tests. All 36 patients underwent conventional magnetic
      resonance (MR) imaging and DWI within the first 24 hours of birth; survivors
      underwent repetitive imaging exams at the end of the first week and then after a
      month. RESULTS: Seventeen stage I cases (47%), 12 stage II cases (33%), and 7
      stage III cases (20%) were detected. DWI obtained within the first 24 hours
      showed high sensitivity (100%) in detecting the permanent neurological sequelae
      but with very low specificity (20%). The negative predictive value of DWI in this
      period was 100%; however, in DWI obtained at the end of the first month, not only
      its sensitivity was preserved, but its specificity reached 80%. The negative
      predictive value of DWI in this period was preserved and the positive predictive
      value improved. The importance of DWI in detecting sequelae at the end of the
      first month was also demonstrated by McNemar (p=0.250) and Kappa (Kappa=0.719)
      tests. There was no difference between conventional MR imaging and DWI in
      detecting sequelae at the end of first month. CONCLUSION: DWI is superior to
      other imaging modalities in detecting ischemia; not only because of its high
      sensitivity in the early phase, but also because of its high sensitivity and
      specificity in the late phase. Moreover, with its high negative predictive value,
      DWI can be used for excluding the possibility of sequelae development in the
      early phase of HIE cases for medico-legal purposes.

PMID- 16972214
TI  - Evaluation of parenchymal changes at the operation site with early postoperative
      brain diffusion-weighted magnetic resonance imaging.
AB  - PURPOSE: To evaluate diffusion changes in the brain parenchyma at the operation
      site during the first 24 hours following surgery. MATERIALS AND METHODS: The
      study group consisted of 52 patients, 39 who had tumor resection surgery and 13
      who had epilepsy surgery. Early postoperative magnetic resonance imaging (MRI)
      included diffusion-weighted imaging (DWI) and routine contrast-enhanced cranial
      MRI, together with T2* weighted images on a 3T system. DWI findings and the
      presence of hemorrhage in the brain parenchyma were evaluated. Correlation
      between the findings, the primary lesion leading to surgery, and operation site
      were evaluated. RESULTS: Diffusion restriction in the parenchyma surrounding the
      resection cavity was seen in 17 tumor patients (32.7%, n=52) and in 8 epilepsy
      patients (15.4%, n=52). DWI showed increased diffusion in 7 patients and no
      abnormality in 4 patients. Twenty patients showed restricted diffusion pattern
      related to hemorrhage (38.5%, n=52). CONCLUSION: Restricted diffusion was the
      most common abnormality observed in the early postoperative DWI of brain
      parenchyma at the operation site after surgery, which suggested tissue injury
      caused by surgery. Yet, hemorrhaging in the operation bed can constitute another
      cause of a reduced apparent diffusion coefficient (ADC) value. Increased
      diffusion and normal diffusion can also be observed, though rarely.

PMID- 16972215
TI  - Organizing pneumonia after radiation therapy for breast cancer.
AB  - We report a case of organizing pneumonia (OP) that developed after radiation
      therapy (RT) for breast cancer. A 54-year-old woman presented with malaise and
      fever within a month after the completion of RT for breast cancer. Chest
      radiographs and computed tomography (CT) demonstrated consolidation in the left
      upper lobe consistent with radiation pneumonia. The patient was given 60 mg/day
      IV cortisone for 15 days after which her complaints and consolidation in the left
      upper lobe disappeared. The daily dose of her corticosteroid was tapered down to
      20 mg/day. Two weeks later, the patient again had fever and malaise. Chest X-ray
      and CT revealed bilateral pulmonary opacities located outside the irradiated
      fields, predominantly in the middle and lower lung zones. The patient's
      laboratory tests were normal except for her erythrocyte sedimentation rate, which
      was elevated. Bronchial lavage revealed moderate elevation of the total cell
      number with lymphocyte predominance. Open lung biopsy was performed and
      histopathological examination demonstrated findings consistent with OP. High dose
      (60 mg/day) prednisolone treatment resulted in rapid clinical and radiological
      improvement. When the prednisolone dose was gradually tapered down to 20 mg/day
      during follow-up, new pulmonary opacities developed in both lungs, as well as the
      recurrence of the patient's symptoms. Increased dose of prednisolone resulted in
      the rapid improvement of the clinical symptoms and radiological abnormalities. OP
      rarely presents after RT for breast and lung cancer. One should always consider
      OP in the clinical setting of a patient who has a history of RT completed 3-6
      months prior to fever, multiple areas of consolidation, and ground glass
      opacities outside the RT field.

PMID- 16972216
TI  - Evaluation of the splenic vein diameter and longitudinal size of the spleen in
      patients with Gamna-Gandy bodies.
AB  - PURPOSE: The aim of this retrospective study was to compare the splenic vein
      diameter and longitudinal size of the spleen in patients with portal hypertension
      in whom Gamna-Gandy bodies were present in their spleen with those of cirrhotic
      patients without Gamna-Gandy bodies and a control group. MATERIALS AND METHODS:
      Between July 2001 and February 2006, patients in whom Gamna-Gandy bodies were
      detected in their spleen and the number of patients who had been undergone
      magnetic resonance (MR) imaging with the diagnosis of chronic liver disease were
      determined. A total of 43 cases with Gamna-Gandy bodies were noted. Out of these
      patients, a case of lymphoma was excluded from the study. Additional 3 cases with
      splenic vein thrombosis were not included in statistical analysis. Accordingly,
      the splenic vein diameter and longitudinal size of the spleen in 39 patients
      (group 1: 12 women, 27 men; mean age, 38.5 years) with portal hypertension in
      whom Gamna-Gandy bodies were detected in their spleen on T1-weighted gradient
      echo MR images between July 2001 and February 2006 were measured. The values
      obtained were compared with those of 29 cirrhotic patients without Gamna-Gandy
      bodies (group 2: 14 women, 15 men, mean age 48.2 years) and control group (group
      3: 13 women, 18 men, mean age 46.8 years). The differences between the groups
      were analyzed with ANOVA and student-t test. RESULTS: Gamna-Gandy bodies were
      detected in 6.3% (42/670) of patients with chronic liver disease. The mean
      longitudinal axis of the spleen (20.2+/-4.2 cm) in group 1 was significantly
      greater (p<0.001) than in group 2 (14.4+/-3.9 cm). The mean splenic vein diameter
      was significantly larger in group 1 (14.3+/-4.0 mm) than those in groups 2 and 3
      (11.2+/-3.2 mm and 7.8+/-1.4 mm, respectively). CONCLUSION: The splenic vein
      diameter and longitudinal size of the spleen in portal hypertensive patients with
      Gamna- Gandy bodies are significantly larger than that of cirrhotic patients
      without Gamna-Gandy bodies and that of control group.

PMID- 16972218
TI  - Floating ball appearance in ovarian cystic teratoma.
AB  - The presence of floating fat balls or globules in an ovarian cystic teratoma is
      an unusual finding. Herein, we present ultrasonographic and tomographic findings
      of a rarely reported case of cystic teratoma with a floating fat ball.

PMID- 16972217
TI  - Focal liver lesions evaluated by MR imaging.
AB  - Magnetic resonance signal intensity of focal liver lesions is the result of their
      histological and cytological features. Therefore, analysis of lesion signal
      intensity and enhancement patterns obtained with magnetic resonance imaging is
      essential for the differential diagnosis of focal liver lesions. In this article,
      we review the magnetic resonance imaging features of the most common focal liver
      lesions.

PMID- 16972219
TI  - Multifocal skeletal tuberculosis involving the lumbar spine and a sacroiliac
      joint: MR imaging findings.
AB  - Sacroiliac joint tuberculosis is rare; its coexistence with vertebral
      tuberculosis is even rarer, with only a few such patients reported in the
      literature. We present magnetic resonance (MR) imaging findings of a patient with
      vertebral and sacroiliac joint tuberculosis, who had paravertebral, iliopsoas,
      and buttock abscesses accompanied by a gluteal pus-draining sinus tract. MR
      imaging is the most sensitive and specific imaging modality for diagnosing
      sacroiliitis at its early stage. Sacroiliac joint tuberculosis can reach advanced
      stages with extensive joint destruction and periarticular abscesses if diagnosis
      and treatment are delayed. A high index of clinical suspicion is required for an
      early diagnosis. The addition of a coronal SPIR T2-weighted sequence to the
      routine MR imaging evaluation of patients studied for lumbar disk disease may be
      useful for recognizing sacroiliac joint pathology at an earlier stage.

PMID- 16972220
TI  - Effects of overweight on luminal diameter, flow velocity and intima-media
      thickness of carotid arteries.
AB  - PURPOSE: To the best of our knowledge, there are only a few previous studies on
      the effects of overweight on extracranial carotid arteries. We aimed to
      investigate the effects of overweight on flow velocities, luminal diameters and
      intima media thicknesses (IMTs) of the common and internal carotid arteries (CCA,
      ICA). MATERIALS AND METHODS: A prospective study on color duplex sonography of
      the extracranial arteries was performed in 71 adults, ages between 25-58 years
      old. The body mass index (BMI) was found to be normal in 24 (group 1) and high in
      47 (group 2) subjects of the study group. Flow velocity (FV), luminal diameter
      and IMT of carotid arteries of all the participants were measured. RESULTS: There
      were significant differences between group 1 and group 2 in the following
      parameters; luminal diameters of the right CCAs were significantly larger in
      group 2, peak-systolic FV of ICAs were significantly lower in group 2 than in
      group 1 and ICA end-diastolic FVs were significantly lower in group 2 than in
      group 1. CONCLUSION: The present data shows that there is a correlation among
      carotid artery luminal diameter, FVs and overweight. In the overweight subjects,
      the increased luminal diameter and decreased FVs can point at the early stage of
      atherosclerosis. The influence of adiposity on atherosclerosis is very complex
      and varies with gender and age, therefore we need larger series and further
      investigation.

PMID- 16972221
TI  - Unenhanced multidetector CT evaluation of urinary stones and secondary signs in
      pediatric patients.
AB  - PURPOSE: This retrospective study evaluated the unenhanced multi-detector
      computed tomography (MDCT) findings of urinary system calculi and the secondary
      signs associated with ureteral stones in children. MATERIALS AND METHODS: The
      study included 87 children (54 boys, 32 girls) with a mean age of 89 months
      (range: 5 months to 16 years) who were referred to us from various departments
      and were evaluated with unenhanced MDCT between January 2004 and June 2005. The
      patients were retrospectively evaluated by 2 radiology specialists by means of
      PACS (picture archiving and communication systems) with regard to the presence of
      stones, and localization and secondary signs associated with ureteral stones,
      such as hydronephrosis, proximal ureteral dilatation, unilateral renal
      enlargement, perinephric edema, tissue rim sign, decreased renal density, and
      periureteral edema. Patients were scanned by 4- and 16-slice MDCT. RESULTS:
      Urinary system calculi were detected in 47 (54%) children. An isolated stone in
      the urinary bladder was detected in one patient. In the remaining 46 children, 43
      of the detected stones were renal stones and 23 of them were ureteral stones.
      Secondary signs associated with ureteral stones were detected in 69.6% of
      children who had ureteral stones. CONCLUSION: MDCT provided evaluation of the
      secondary signs associated with ureteral stones as well as the direct
      visualization of the stones in cases with urinary stone disease. The ability of
      MDCT to detect the secondary signs associated with ureteral stones supported the
      diagnoses and may aid in diagnosis when difficulties are present.

PMID- 16972222
TI  - Angiographic findings and endovascular embolization in Dieulafoy disease: a case
      report and literature review.
AB  - Dieulafoy disease is an unusual cause of gastrointestinal (GI) hemorrhage that
      can be fatal. It arises from an abnormally large eroded submucosal artery
      commonly located in the proximal stomach. Since this disease first described in
      1884, it has been rarely discussed in radiology literature. We describe a case of
      an elderly patient with multiple medical problems presented with upper and lower
      GI hemorrhage. Repeated upper GI endoscopies revealed a large fundal clot but
      otherwise were unremarkable. Angiography showed anomalous short gastric artery
      originating normally from the splenic artery. The latter was embolized with
      microcoils and Gelfoam. Following embolization, the frequency and amount of
      bleeding decreased although did not totally stop and the patient underwent
      elective partial gastrectomy. The diagnosis was made histologically. Therefore,
      Dieulafoy disease can represent a diagnostic and therapeutic challenge. It should
      be suspected if a patient with GI hemorrhage is found to have extravasation from
      a dilated tortuous artery that appears normal otherwise with no associated large
      draining veins. Transcatheter selective arterial embolization has a reported role
      in the literature as a less invasive therapeutic option compared to surgery.

PMID- 16972223
TI  - Evaluation of radiotherapy response of cervical carcinoma with gray scale and
      color Doppler ultrasonography: resistive index correlation with magnetic
      resonance findings.
AB  - PURPOSE: To investigate the role of the resistive index measured with
      transvaginal color Doppler ultrasonography (TVCDUS) for assessing the
      radiotherapy response of cervical carcinoma and to compare it with magnetic
      resonance findings. MATERIALS AND METHODS: A total of 13 patients with advanced
      stage cervical carcinoma (>IIA) underwent magnetic resonance imaging (MRI) and
      TVCDUS exams 6 months prior to and 6 months after radiotherapy. Pre- and post
      treatment resistive indices obtained from the central and peripheral zones of the
      tumor were compared. These values were also compared with MRI findings and
      resistive indices obtained from the control group. RESULTS: Tumoral masses could
      be visualized in all patients with B-mode TVCDUS prior to the treatment.
      Resistive indices before and after treatment were 0.20-0.82 (mean: 0.52+/-0.15),
      and 0.70-0.99 (mean: 0.81+/-0.14), respectively. Eleven out of 13 patients
      responded to the treatment completely and no mass was detected in MRI and TVCDUS.
      Investigations were performed in areas with flow within the tumor-free cervix. A
      residual mass was noted in 2 patients with MRI and TVCDUS. There was a
      statistically significant difference between complete response to the treatment
      and increased resistive indices (P=0.001). In 2 patients with residual masses, no
      increase in resistive indices was detected. The mean resistive index of the
      control group was 0.65+/-13 and the difference was statistically significant
      compared to the resistive indices of the patients prior to the treatment.
      CONCLUSION: Since there was a significant correlation between the MRI findings
      and resistive indices, the spectral parameters obtained with TVCDUS were a good
      alternative to such an expensive modality as MRI in the evaluation of the
      response of cervical cancer to the treatment.

PMID- 16972224
TI  - Perceived parenting behavior in the childhood of cocaine users: relationship with
      genotype and personality traits.
AB  - Low parental care during childhood, a pattern characteristic of an "affectionless
      control" rearing style was frequently reported in the history of addicted
      individuals. Parents' childrearing regimes and children's genetic
      predispositions, with their own behavioral characteristics, have been seen to be
      closely interwoven, probably affecting children's development and addictive
      behavior susceptibility. In the present study, parents care perception,
      aggressive personality traits, and genotype (serotonin transporter promoter gene-
      5-HTTLPR) have been investigated in cocaine users and healthy control subjects.
      PBI scores (maternal and paternal care) were lower and BDHI scores
      (aggressiveness) higher in cocaine users in comparison with controls and
      significant differences in the perception of either paternal or maternal care
      were observed between cocaine users and non-users. The short-short (SS) genotype
      frequency was significantly higher among cocaine users compared with control
      subjects (P = 0.04). Logistic regression proves that persons bearing the SS
      genotype have a risk of becoming cocaine user almost three times higher than
      those having the LL genotype. Estimations of the effects of other factors
      potentially affecting the risk of being cocaine addicted clearly prove the
      significant impact of aggressiveness: the highest the score, the highest the risk
      of becoming cocaine user. Moreover, paternal and maternal care perception
      significantly improve the fit of the model (the log likelihood decreases passing
      from -105.9 to -89.8, LR test = 32.17, P-value = 0.0000). Each unit increase in
      the PBI score yields a significant 12% and 10% decrease of the risk of becoming
      cocaine user, respectively for paternal and maternal care. Interestingly, once
      controlled for the PBI score, the relative risk associated to the SS genotype
      drops strikingly and becomes no longer statistically significant. On the whole,
      our preliminary data suggest that the association between 5-HT transporter
      polymorphism and psycho-stimulant use may be mediated by mother-child
      relationship and parental attachment perception, both being environmental and
      genetic factors involved in the proneness to substance use disorders,
      particularly in aggressive-antisocial individuals.

PMID- 16972225
TI  - High dose glucocorticoid hampers bone formation and resorption after bone marrow
      ablation in rat.
AB  - We analyzed the effect of glucocorticoid on bone regeneration after bone marrow
      ablation in tibiae of 8-week-old rats. Methylprednisolone sodium succinate (MPSS)
      was injected intramuscularly at a dose of 100 mg/kg/day for 3 days. Tibiae on
      days 1, 3, 5, 7, 10, 12, and 14 after ablation were subjected to tartrate
      resistant acid phosphatase staining, immunohistochemistry, in situ hybridization,
      and transmission electron microscopy (TEM), and measurement of the volume of
      newly-formed bone and the osteoclast number. MPSS significantly decreased the
      newly-formed bone volume on day 7, and immature bone still remained on day 10 in
      the MPSS-treated group. The volume of this bone was significantly higher than
      that in the control group. However, there were no differences between the groups
      in the osteoclast number, the expression of mRNAs for osteoblast differentiation
      markers, and alkaline phosphatase and cathepsin K judged by immunohistochemistry.
      TEM findings showed no difference in the form of osteoblasts, whereas osteoclasts
      in the MPSS-treated group had less developed ruffled borders, compared to those
      in the control group. These results suggest that MPSS treatment affects neither
      the differentiation nor the shape of osteoblasts, and does not change the
      osteoclast number or the cathepsin K level. However, high dose MPSS inhibits both
      bone formation and resorption during bone regeneration after rat tibial bone
      marrow ablation, and inhibits ruffled border formation in osteoclasts. These data
      will be useful to develop bone regenerative therapies for bone diseases due to
      high dose steroid administration.

PMID- 16972226
TI  - Can you trust your cryostat? Reproducibility of cryostat section thickness.
AB  - Reproducibility of cryostat section thickness is required for valid quantitative
      microscopy. This is generally pursued by motorized sectioning using a low but
      constant speed. The purpose of our study was to compare variation in section
      thickness between motorized and manual cryostat sectioning. Serial sections were
      cut from a frozen block of homogenized tissue on different days. Lactate
      dehydrogenase activity was histochemically detected and calibrated absorbance
      measurements were taken. The coefficients of variation of measurements was 9.7%
      for motorized sectioning and 3.3% for manual sectioning. In conclusion, section
      thickness is similarly reproducible after manual sectioning compared with
      motorized sectioning, if not better.

PMID- 16972227
TI  - Spectrum of molecular defects and mutation detection rate in patients with mild
      and moderate hemophilia A.
AB  - The amount of residual F8 (FVIII:C) determines the clinical severity of
      hemophilia A. Recently, we showed that the mutation detection rate in severely
      affected male patients (FVIII:C<1% of normal) is virtually 100% when testing for
      the common intron 22-/intron 1- inversions and big deletions, followed by genomic
      sequencing of the F8 gene. Here we report on the spectrum of mutations and their
      distribution throughout the F8 gene sequence in 135 patients with moderate (n=23)
      or mild (n=112) hemophilia A. In contrast to the severe form of the disorder,
      analysis on the genomic level failed to detect the molecular defect in
      approximately 4% of the moderately and in approximately 12% of the mildly
      affected patients. A total of 36 of the mutations identified in this study are
      novel. The vast majority of the detected changes were missense. The newly
      detected amino acid substitutions were scored for potential distant or local
      conformational changes and influence on molecular stability for every single F8
      domain with available structures, using homology modeling. Two molecular changes
      in the promoter region of the factor VIII gene (c.-112G>A and -219C>T), affecting
      the core segment (minimal promoter) were detected in two patients with mild
      hemophilia A. To our knowledge this is the first report on promoter mutations in
      the F8 gene.

PMID- 16972228
TI  - Mineralocorticoid receptor mutations are the principal cause of renal type 1
      pseudohypoaldosteronism.
AB  - Aldosterone plays a key role in electrolyte balance and blood pressure
      regulation. Type 1 pseudohypoaldosteronism (PHA1) is a primary form of
      mineralocorticoid resistance characterized in the newborn by salt wasting,
      hyperkalemia, and failure to thrive. Inactivating mutations of the
      mineralocorticoid receptor (MR; NR3C2) are responsible for autosomal dominant and
      some sporadic cases of PHA1. The question as to whether other genes may be
      involved in the disease is of major importance because of the potential life
      threatening character of the disease, the potential cardiovascular effects of
      compensatory aldosterone excess, and the role of the mineralocorticoid system in
      human hypertension. We present the first comprehensive study seeking nucleotide
      substitutions in coding regions, intron-exon junctions, and untranslated exons,
      as well as for large deletions. A total of 22 MR gene abnormalities were found in
      33 patients. We demonstrate that MR mutations are extremely frequent in PHA1
      patients classified according to aldosterone and potassium levels and give
      indications for accurate clinical and biological investigation. In our study the
      possibility of a genocopy exists in three PHA1 kindreds. The other patients
      without MR mutations might have different diseases resembling to PHA1 in the
      neonatal period, which could be identified by extensive clinical and functional
      exploration.

PMID- 16972229
TI  - Chronic granulomatous disease caused by mutations other than the common GT
      deletion in NCF1, the gene encoding the p47phox component of the phagocyte NADPH
      oxidase.
AB  - Chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by
      defects in any of four genes encoding components of the leukocyte nicotinamide
      dinucleotide phosphate, reduced (NADPH) oxidase. One of these is the autosomal
      neutrophil cytosolic factor 1 (NCF1) gene encoding the p47phox protein. Most
      (>97%) CGD patients without p47phox (A47 degrees CGD) are homozygotes for one
      particular mutation in NCF1, a GT deletion in exon 2. This is due to
      recombination events between NCF1 and its two pseudogenes (psiNCF1) that contain
      this GT deletion. We have previously set up a gene-scan method to establish the
      ratio of NCF1 genes and pseudogenes. With this method we now found, in three CGD
      families patients with the normal number of two intact NCF1 genes (and four
      psiNCF1 genes) and in six CGD families, patients with one intact NCF1 gene (and
      five psiNCF1 genes). All patients lacked p47phox protein expression. These
      results indicate that other mutations were present in their NCF1 gene than the GT
      deletion. To identify these mutations, we designed PCR primers to specifically
      amplify the cDNA or parts of the genomic DNA from NCF1 but not from the psiNCF1
      genes. We found point mutations in NCF1 in eight families. In another family, we
      found a 2,860-bp deletion starting in intron 2 and ending in intron 5. In six
      families the patients were compound heterozygotes for the GT deletion and one of
      these other mutations; in two families the patients had a homozygous missense
      mutation; and in one family the patient was a compound heterozygote for a splice
      defect and a nonsense mutation. Family members with either the GT deletion or one
      of these other mutations were identified as carriers. This knowledge was used in
      one of the families for prenatal diagnosis.

PMID- 16972230
TI  - Human articular chondrocytes suppress in vitro proliferation of anti-CD3
      activated peripheral blood mononuclear cells.
AB  - OBJECTIVE: To investigate whether mature human articular chondrocytes (AC)
      exhibit an antiproliferative effect on activated peripheral blood mononuclear
      cells (PBMC) and to compare this effect with other cells of mesenchymal origin.
      METHODS: AC from healthy cadaveric cartilage were grown for different passages,
      in the absence (control) or presence of factors enhancing cell de-differentiation
      (transforming growth factor (TGF)beta1, fibroblast growth factor (FGF)-2, and
      platelet derived growth factor (PDGF)bb-TFP medium). Cell ability to suppress
      PBMC proliferation driven by anti-CD3 antibody was measured by tritiated
      thymidine uptake following incubation for 48 h at different PBMC:AC ratios and
      expressed as percent of residual proliferation (RP). AC antiproliferative effect
      was compared to that of control dermal fibroblasts (DF) and bone marrow stromal
      cells (BMSC). RESULTS: AC exhibited a cell number-dependent antiproliferative
      effect. The strongest effect (up to 2% RP) was measured using the least expanded
      AC cultures. The use of TFP medium for AC expansion resulted in a significantly
      lower antiproliferative effect, in the range of that induced by BMSC (up to 18%
      RP). Also DF induced a marked antiproliferative effect (up to 11% RP).
      CONCLUSION: We report for the first time that human AC have a marked
      antiproliferative effect on anti-CD3 stimulated PBMC, which is reduced upon
      culture in medium-inducing extensive cell de-differentiation. These results
      reflect the immunosuppressive properties observed for other different mesenchymal
      cell types and raise the question of a potential common physiological role in
      local tissue protection.

PMID- 16972231
TI  - Tissue characterization of myocardial infarction using T1rho: influence of
      contrast dose and time of imaging after contrast administration.
AB  - PURPOSE: To determine whether contrast between acutely infarcted and normal
      myocardia in T1-rho-weighted cine TFE (T1rho-TFE) and delayed-enhancement (DE)
      images (measured using a metric percent enhancement (PE)) varied with the dose or
      time of imaging after contrast administration. MATERIALS AND METHODS: Eighteen
      patients with acute myocardial infarction (AMI) were randomly divided into three
      groups according to the dose of gadoversetamide (0.1, 0.2, or 0.3 mmol/kg)
      administered. After contrast administration, T1rho-TFE images were acquired at
      five and 40 minutes, and DE images were acquired at 10 and 30 minutes. RESULTS:
      For T1rho-TFE imaging the PE values at 40 minutes were 70+/-14, 98+/-14, and
      105+/-41 at 0.1, 0.2, and 0.3 mmol/kg dose levels, which were significantly
      greater than the corresponding PEs at five minutes after contrast administration
      (44+/-12, 71+/-14, and 36+/-13). For DE and T1rho-TFE imaging the dose of
      contrast agent did not significantly affect the PE. However, with DE the PE
      tended to increase with the dose. At all dose levels, irreversible injury was
      more conspicuous in T1rho-TFE images acquired at 40 minutes than at five minutes
      after contrast. CONCLUSION: In T1rho-TFE, acute infarction was more conspicuous
      in images acquired at a later time point, and the PE did not vary with the
      contrast dose.

PMID- 16972232
TI  - Sensory, motor somatic, and autonomic neurons projecting to the porcine cremaster
      muscle.
AB  - The location of sensory, somatic, and autonomic neurons projecting to the pig
      cremaster muscle (CM) was studied by means of the retrograde neuronal tracer Fast
      Blue (FB) technique. FB was randomly injected in the left CM of four impuberal
      pigs and serial sections of sensory and autonomic ganglia and spinal cord were
      examined under a fluorescence microscope. Additionally, some indications about
      the number and size of labeled neurons were given. Sensory pseudounipolar somata
      were located ipsilaterally in the L2-L6 and S1-S2 dorsal root ganglia, their
      total number ranging between 125 and 194, their mean diameter between 24 and 89
      microm. Somatic multipolar motoneurons were located ipsilaterally in the L2-L4
      neuromeres of the spinal cord, their total number ranging between 53 and 169,
      their mean diameter between 29 and 53 microm. Autonomic multipolar paravertebral
      ganglia neurons were located ipsilaterally from L1 to S4 and contralaterally from
      L2 to S2. Their total number ranged from 2,015 to 3,067 and their mean diameter
      between 25 and 55 microm. The multipolar caudal mesenteric ganglia neurons were
      located bilaterally, their total number ranging between 14 and 1,408 and their
      diameter from 22 to 39 microm. In two subjects only, multipolar neurons were also
      found ipsilaterally in the microganglia of pelvic plexus (2 and 13 neurons).
      Their mean diameter ranged between 28 and 54 microm. Our study documented that
      the CM-projecting neurons were located at different neural levels, with a
      predominance in the autonomic ganglia.

PMID- 16972233
TI  - Q-FIHC: quantification of fluorescence immunohistochemistry to analyse p63
      isoforms and cell cycle phases in human limbal stem cells.
AB  - Fluorescence microscopy has long been used for qualitative characterization of
      various parameters such as subcellular distribution of proteins, lipids, nucleic
      acids, and ions. However, quantification of these parameters is complicated by a
      variety of optical, biological, and physical factors. In the last decade, the
      progress achieved with powerful softwares and digital image processing systems
      has facilitated the development of fluorescence immunohistochemistry (FIHC) into
      a widely used quantitative assay (quantitative-FIHC or Q-FIHC). We describe here
      a rapid and sensitive Q-FIHC assay based on the use of a laser scanning confocal
      microscope and advanced image analysis softwares (Zeiss semi automatic LSM 510
      and fully automatic Axiovision 4.4) for the detection and quantification of
      fluorescent intensity in human corneal tissues and cells obtained from small
      clinical samples. We have used this methodology to characterize and quantify the
      gene expression profile of p63 and its DeltaNalpha isoform, specific markers of
      human limbal stem cells. The validity of this method was evaluated through
      comparative studies with conventional approaches suggesting no significant
      differences and providing an alternative technique to traditional methods. Since
      Q-FIHC requires at least 20-fold less cells than traditional techniques, we have
      adopted it as the main quality control for our limbal cultures destined to
      clinical application.

PMID- 16972234
TI  - Intact corneal stroma visualization of GFP mouse revealed by multiphoton imaging.
AB  - The aim of this work is to demonstrate that multiphoton microscopy is a preferred
      technique to investigate intact cornea structure without slicing and staining. At
      the micron resolution, multiphoton imaging can provide both large morphological
      features and detailed structure of epithelium, corneal collagen fibril bundles
      and keratocytes. A large area multiphoton cross-section across an intact eye
      excised from a GFP mouse was obtained by a homebuilt multiphoton microscope. The
      broadband multiphoton fluorescence (435-700 nm) and second harmonic generation
      (SHG, 360-400 nm) signals were generated by the 760 nm output of a femtosecond
      titanium-sapphire laser. A water immersion objective (Fluor, 40X, NA 0.8; Nikon)
      was used to facilitate imaging the curve ocular surface. The multiphoton image
      over entire cornea provides morphological information of epithelial cells,
      keratocytes, and global collagen orientation. Specifically, our planar, large
      area multiphoton image reveals a concentric pattern of the stroma collagen,
      indicative of the laminar collagen organization throughout the stroma. In
      addition, the green fluorescence protein (GFP) labeling contributed to
      fluorescence contrast of cellular area and facilitated visualizing of inactive
      keratocytes. Our results show that multiphoton imaging of GFP labeled mouse
      cornea manifests both morphological significance and structural details. The
      second harmonic generation imaging reveals the collagen orientation, while the
      multiphoton fluorescence imaging indicates morphology and distribution of cells
      in cornea. Our results support that multiphoton microscopy is an appropriate
      technology for further in vivo investigation and diagnosis of cornea.

PMID- 16972235
TI  - Case-control and within-family tests for an association between conduct disorder
      and 5HTTLPR.
AB  - Several lines of research have suggested that serotonin dysfunction is associated
      with aggression, impulsivity, and antisocial behavior. A functional polymorphism
      in the promoter region (s, short and l, long allele variant) of the serotonin
      transporter gene (SLC6A4) that results in decreased transcription of the
      serotonin transporter gene has been linked with such serotonin dysfunction. To
      test for an association between 5HTTLPR genotype and conduct disorder
      diagnosis/aggression. Analysis for association between 5HTTLPR and conduct
      disorder/aggression using a case-control design and the transmission
      disequilibrium test. Conduct-disordered adolescents, who were drawn from
      admissions to a program that treats adolescents with serious substance and
      behavior problems, and conduct-disordered siblings of these patients (n, 297)
      were compared with non-conduct-disordered control adolescents and non-conduct
      disordered siblings of these controls (n, 93). Second, using patient families
      where parental DNA was available, transmission disequilibrium tests were
      conducted for two phenotypes: (1) conduct disorder (74 trios), and (2) conduct
      disorder with at least one aggressive symptom (57 trios). Case-control analyses
      suggested a strong association between the ss genotype and conduct disorder
      (chi2(2) = 14.3; P < 0.01). Within-family analyses for conduct disorder with at
      least one aggressive symptom significantly favored greater transmission of the s
      allele to affected offspring (chi(tdt)(2) = 4.13; P = 0.04); for conduct
      disorder, without aggressive symptoms, however, results were non-significant
      (chi(tdt)(2) = 1.61; P = 0.20). These data suggest that the s-allele may confer
      some risk for aggressive behavior or may be in linkage disequilibrium with such
      an allele.

PMID- 16972236
TI  - Clinical response to varying the stimulus parameters in deep brain stimulation
      for essential tremor.
AB  - Deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus
      for essential tremor is sometimes limited by side effects. The mechanisms by
      which DBS alleviates tremor or causes side effects are unclear; thus, it is
      difficult to select stimulus parameters that maximize the width of the
      therapeutic window. The goal of this study was to quantify the impact on side
      effect intensity (SE), tremor amplitude, and the therapeutic window of varying
      stimulus parameters. Tremor amplitude and SE were recorded at 40 to 90
      combinations of pulse width, frequency, and voltage across 14 thalami. Posterior
      variable inclusion probabilities indicated that frequency and voltage were the
      most important predictors of both SE and tremor amplitude. The amount of tremor
      suppression achieved at frequencies of 90 to 100 Hz was not different from that
      at 160 to 170 Hz. However, the width of the therapeutic window decreased
      significantly and power consumption increased as frequency was increased above 90
      to 100 Hz. Improved understanding of the relationships between stimulus
      parameters and clinical responses may lead to improved techniques of stimulus
      parameter adjustment.

PMID- 16972237
TI  - Juxtaglomerular cell tumor in an 8-year-old girl.
AB  - Juxtaglomerular cell tumor (JGCT) is an extremely rare renal neoplasm in the
      pediatric population. It is considered a benign tumor arising from the
      juxtaglomerular apparatus of the kidney. JGCT has characteristic
      clinicopathologic features, but its cytogenetic features are unknown. We report a
      case of JGCT in an 8-year-old female who presented with severe hypertension,
      elevated serum renin level, and a well circumscribed tumor in the right kidney.
      Protogranules of renin was identified in the cytoplasm of the tumor cells by
      electron microscopic examination. Fluorescence in situ hybridization revealed
      monosomy of chromosomes X, 6, 9, 11, 15, and 21.

PMID- 16972238
TI  - Involuntary painful muscle contractions in Satoyoshi syndrome: a surface
      electromyographic study.
AB  - We report a child with Satoyoshi syndrome manifested by involuntary painful
      muscle contractions and alopecia. Although an autoimmune origin of Satoyoshi
      syndrome seems likely, its exact etiology remains as yet unknown, as is the
      origin of the involuntary contractions. To gain a better understanding of the
      electrophysiological characteristics of the involuntary contractions, we
      performed a surface electromyographic (EMG) study. We investigated muscle
      contractions in the legs using two noninvasive techniques: high-density surface
      EMG (HD-sEMG) recordings on one muscle, and polymyographic surface EMG (sEMG)
      recordings on various muscles. During the involuntary contractions, HD-sEMG
      showed a fourfold increase in amplitude compared to maximal voluntary
      contractions. These high potentials were widely distributed across the whole
      muscle and showed a pronounced oscillatory behavior with a frequency around 45
      Hz. Polymyographic sEMG revealed that the involuntary contractions often occur
      simultaneously in various muscles or showed a switch of activity from one muscle
      to another. These findings point to hyperactivity or a disinhibition at the alpha
      motor neuron level, originating probably at that level, although a central origin
      cannot be excluded. (c) 2006 Movement Disorder Society.

PMID- 16972240
TI  - Treatment of pediatric non-Hodgkin lymphomas in a country with limited resources:
      results of the first national protocol in Nicaragua.
AB  - We report the results of a protocol for the diagnosis and treatment of pediatric
      non-Hodgkin lymphomas (NHL) conducted in Nicaragua in the context of an
      international collaborative program. Fifty-three children with NHL treated
      between 1996 and 2003 were retrospectively evaluated. Therapy was designed based
      on local drug availability and affordability with dose and schedule adaptations
      for Burkitt and lymphoblastic lymphomas. With a median follow-up of 3 years, the
      projected 9-year overall survival was 63% and event-free survival 53%. The
      treatment was efficacious, feasible, and well tolerated in spite of the local
      socio-economical conditions.

PMID- 16972239
TI  - Symptoms in the palliative phase of children with cancer.
AB  - BACKGROUND: The aim of the study was to make a comprehensive inventory of the
      physical, psychological, and social symptoms of children with cancer and their
      parents during the palliative phase and the extent to which health professionals
      address those symptoms. PROCEDURE: Forty parents of children who died 1-3 years
      prior to data collection (structured questionnaire) were invited to participate
      in the study. RESULTS: The response rate was 32 out of 40 parents (80%). Most
      frequently mentioned physical symptoms were pain, poor appetite, and fatigue. The
      children's most mentioned psychological symptoms were sadness, difficulty in
      talking to their parents about their feelings regarding illness and death and
      fear of being alone. The symptoms of fear of death of the child and fear of
      physical symptoms were most frequently mentioned parents' psychological symptoms.
      Health professionals addressed 82% of the children's physical symptoms, 43% of
      the children's psychological symptoms, and 56% of the parents' psychological
      symptoms. Parents indicated that after professional attention the proportion of
      children's physical symptoms that were completely or partially resolved was 18
      and 26%, respectively. For children's psychological symptoms the figures were 9
      and 25%, respectively, and for parents' psychological symptoms 2 and 23%,
      respectively. CONCLUSIONS: The burden of symptoms of the child with cancer during
      the palliative phase and their parents is high. Health professionals focus mainly
      on the physical symptoms of the child. Relief of symptoms could not be achieved
      for a large proportion of symptoms. Further prospective research is necessary to
      investigate the kind, frequency and intensity of symptoms in order to tailor
      optimal palliative care to the needs of both child and parent.

PMID- 16972241
TI  - Survival, mortality, and complications in patients with beta-thalassemia major in
      northern Taiwan.
AB  - BACKGROUND: Advances in treatment have improved the prognosis in beta-thalassemia
      major. We present the survival and complications pattern of those patients in
      northern Taiwan born after 1970. PROCEDURE: One-hundred and sixty patients with
      beta-thalassemia major born after 1970 were collected. The Kaplan-Meier method
      and log-rank test were used to estimate and compare survival. Cox regression
      models were used to examine the associations of bone marrow transplantation
      (BMT), time of BMT procedure, and time of complications with survival. RESULTS:
      Better survival was observed for patients born after 1980 (P = 0.0121). Heart
      disease, BMT-related deaths, and infections were the main causes of death. Among
      the living patients over age 15, hypogonadotropic hypogonadism, HCV infection,
      diabetes, heart failure, and arrhythmia were the common complications. No
      patients under age 15 had complications. CONCLUSIONS: Survival for patients with
      beta-thalassemia major has improved significantly in Taiwan. More time is
      required to demonstrate whether these modalities added to the treatment of these
      patients will impact favorably on their outcome. Our success with BMT is
      improving and we are now in a position to offer this curative alternative.

PMID- 16972242
TI  - A pilot phase II study of alternate day ganciclovir and foscarnet in preventing
      cytomegalovirus (CMV) infections in at-risk pediatric and adolescent allogeneic
      stem cell transplant recipients.
AB  - BACKGROUND: Prophylaxis with ganciclovir or foscarnet post allogeneic stem cell
      transplant (AlloSCT) reduces cytomegalovirus (CMV) disease. Combination
      ganciclovir/foscarnet is more effective than monotherapy in HIV patients with CMV
      retinitis. We hypothesized that alternate day ganciclovir and foscarnet for the
      prevention of CMV during the first 100 days after AlloSCT would be safe and
      effective. PROCEDURE: Fifty-three pediatric and adolescent AlloSCT recipients
      receiving 57 AlloSCTs where donors and/or recipients were CMV seropositive
      received ganciclovir (5 mg/kg/48 hr) alternating with foscarnet (90 mg/kg/48 hr)
      from myeloid recovery (>or=ANC 750/mm3) until Day +100. RESULTS: Patients were:
      M:F 31:22; age 6 years (0.8-18 years); donor sources: 25 related peripheral
      blood/bone marrow, 3 unrelated adult peripheral blood, 26 unrelated cord blood,
      and 3 related cord blood. GVHD prophylaxis included tacrolimus/mycophenolate
      mofetil (MMF). Median-nucleated and CD34 cell counts were 7.3x10(8)/kg and
      5.07x10(6)/kg, respectively, for BM/PBSC; 4.07x10(7)/kg and 1.69x10(5)/kg,
      respectively, for CB. Despite a 36.5% probability of Grades II-IV acute GVHD, no
      patient developed systemic CMV disease. Five percent had Grade IV hematological
      toxicity that required discontinuation of ganciclovir. Twenty-five percent
      required discontinuation of foscarnet secondary to electrolyte abnormalities
      and/or renal dysfunction that were presumed to be multifactorial in origin.
      Probability of 1-year overall survival was 58.8%. CONCLUSIONS: Alternate day
      ganciclovir/foscarnet in AlloSCT recipients where recipient and/or donor is
      seropositive appears to be tolerable and 100% effective in preventing CMV
      systemic disease. A randomized study will be required to determine if this
      approach is superior to other CMV prophylactic designs.

PMID- 16972243
TI  - A phase II trial of thalidomide and cyclophosphamide in patients with recurrent
      or refractory pediatric malignancies.
AB  - BACKGROUND: Previous clinical and pre-clinical research has demonstrated synergy
      between anti-angiogenic agents and cytotoxic chemotherapy. This trial was
      undertaken to investigate whether the combination of cyclophosphamide and
      thalidomide would be active against pediatric tumors. PROCEDURE: Patients with
      pediatric malignancies who had no remaining conventional therapeutic options were
      recruited from January 1999 to May 2001. They received thalidomide (6-12 mg/kg po
      every day; maximum daily dose 800 mg) and cyclophosphamide (1,200 mg/m2 IV every
      28 days). RESULTS: Twenty-seven patients were enrolled on the study. Seventeen
      were male and 10 were female. Median age at the time of registration was 15 years
      (range 1-54 years). The median number of prior treatment regimens was four.
      Twenty-one patients were evaluable for response; 1 had a partial response
      (Hodgkin disease), 1 demonstrated stable disease (neuroendocrine tumor), and 19
      had progressive disease. The most common toxicities were hematological
      (leukocytopenia and neutropenia) and gastrointestinal. One patient experienced a
      grade 3 rash. Fatigue and daytime somnolence were variable. No peripheral
      neuropathy was observed. CONCLUSION: The combination of thalidomide and
      cyclophosphamide as described herein has a modest and tolerable toxicity profile
      but little evidence of efficacy.

PMID- 16972244
TI  - Effect of deep brain subthalamic stimulation on camptocormia and postural
      abnormalities in idiopathic Parkinson's disease.
AB  - Camptocormia has been described in patients with idiopathic Parkinson's disease
      (PD). We present a patient with young-onset PD in whom the disease progressed
      over 25 years to a crippling state with severe camptocormia and bent knees. The
      camptocormia along with other parkinsonian symptoms improved dramatically after
      bilateral subthalamic deep brain stimulation.

PMID- 16972245
TI  - Alpha2beta1 integrin signalling enhances cyclooxygenase-2 expression in
      intestinal epithelial cells.
AB  - Inflammatory bowel diseases (IBD) are linked to an increased risk of developing
      colon cancer, by inflammatory mediators and alterations to the extracellular
      matrix (ECM). The events induced by inflammatory mediators lead to dysregulated
      activation and induction of inflammatory genes such as cyclooxygenase-2 (COX-2).
      COX-2 is involved in the conversion of arachidonic acid to biologically active
      prostanoids and is highly upregulated in colon cancer. Since inflammation-induced
      changes to the extracellular matrix could affect integrin activities, we here
      investigated the effect of integrin signalling on the level of COX-2 expression
      in the non-transformed intestinal epithelial cell lines, Int 407 and IEC-6.
      Adhesion of these cells to a collagen I- or IV-coated surface, increased surface
      expression of alpha2beta1 integrin. Activation of integrins with collagen caused
      an increased cox-2 promoter activity, with a subsequent increase in COX-2
      expression. The signalling cascade leading to this increased expression and
      promoter activity of cox-2, involves PKCalpha, the small GTPase Ras and NFkappaB
      but not Erk1/2 or Src activity. The integrin-induced increase in cellular COX-2
      activity is responsible for an elevated generation of reactive oxygen species
      (ROS) and increased cell migration. This signalling pathway suggests a mechanism
      whereby inflammation-induced modulations of the ECM, can promote cancer
      transformation in the intestinal epithelial cells.

PMID- 16972246
TI  - Myogenic differentiation of dermal papilla cells from bovine skin.
AB  - Cells from the dermal papilla and dermal sheath of hair follicles exhibit
      pronounced plasticity in vitro, being capable of adopting fat, bone,
      hematopoietic, and nerve cell phenotypes. In this study, we show that bovine
      dermal papilla cells (DPC) are also capable of undergoing skeletal muscle
      differentiation. DiI labeled DPC incorporated into myotubes when co-cultured with
      differentiating C(2)C(12) myoblasts. Bovine-specific PCR assays showed that the
      muscle markers MyoD and myogenin were up-regulated, confirming that the DPC had
      adopted a myogenic gene expression program. Nine clonal lines of DPC underwent
      both adipogenic and myogenic differentiation, demonstrating the multipotency of
      individual cells. Primary populations of both DPC and extra-follicular dermal
      fibroblasts were also capable of both adipogenic and myogenic differentiation.
      However, on myogenic differentiation, cells derived from dermal papillae
      expressed higher levels of myogenin than primary fibroblasts derived from extra
      follicular dermis, suggesting that papilla cells undergo myogenesis more
      efficiently. This result shows that populations of fibroblastic cells derived
      from different anatomical sites within the skin are not equivalent with respect
      to their plasticity. Cultured DPC and dermal fibroblasts both expressed Pax3, a
      marker for the dermomyotome which represents a common embryological origin of
      muscle and dermis. Quantitative PCR showed that Pax3 expression levels before
      myogenic induction correlated with myogenin expression levels after myogenesis.
      These results suggest that a degree of dedifferentiation may underlie the
      plasticity of dermal cells in vitro, and that this plasticity may be predicted,
      at least in part, by levels of Pax3 expression.

PMID- 16972247
TI  - Sulfated glycosaminoglycans mediate the effects of FGF2 on the osteogenic
      potential of rat calvarial osteoprogenitor cells.
AB  - Fibroblast growth factor-2 (FGF2) is a powerful promoter of bone growth. We
      demonstrate here that brief exposure to FGF2 enhances mineralized nodule
      formation in cultured rat osteoprogenitor cells due to an expansion of cells that
      subsequently mineralize. This mitogenic effect is mediated via sulfated
      glycosaminoglycans (GAGs), FGFR1, and the extracellular signal-regulated kinase
      (ERK) pathway. The GAGs involved in this stimulation are chondroitin sulfates
      (CS) rather than heparan sulfates (HS). However, continuous FGF2 treatment
      reduces alkaline phosphatase (ALP) activity, downregulates collagen Ialpha1
      (ColIalpha1) and FGFR3 expression, upregulates the expression and secretion of
      osteopontin (OPN) and inhibits mineralization. The inhibitory effects of FGF2 on
      FGFR3 expression and ALP activity are also mediated by the ERK pathway, although
      the effects of FGF2 on ColIalpha1 and OPN expression are mediated by GAGs and PKC
      activity. Thus short-term activation of FGF2/FGFR1 promotes osteoprogenitor
      proliferation and subsequent differentiation, while long-term activation of FGF2
      signaling disrupts mineralization by modulating osteogenic marker expression.
      This study thus establishes the central role of sulfated GAGs in the osteogenic
      progression of osteoprogenitors.

PMID- 16972248
TI  - Self-renewal of human embryonic stem cells is supported by a shortened G1 cell
      cycle phase.
AB  - Competency for self-renewal of human embryonic stem (ES) cells is linked to
      pluripotency. However, there is a critical paucity of fundamental parameters of
      human ES cell division. In this study we show that human ES cells (H1 and H9; NIH
      designated WA01 and WA09) rapidly proliferate due to a very short overall cell
      cycle (15-16 h) compared to somatic cells (e.g., normal diploid IMR90 fibroblasts
      and NT-2 teratocarcinoma cells). The human ES cell cycle maintains the four
      canonical cell cycle stages G1, S, G2, and M, but the duration of G1 is
      dramatically shortened. Bromodeoxyuridine (BrdU) incorporation and FACS analysis
      demonstrated that 65% of asynchronously growing human ES cells are in S phase.
      Immunofluorescence microscopy studies detecting BrdU labeled mitotic chromosomes,
      Ki67 domains, and p220(NPAT) containing Cajal bodies revealed that the durations
      of the S ( approximately 8 h), G2 ( approximately 4 h), and M phases (
      approximately 1 h) are similar in ES and somatic cells. We determined that human
      ES cells remain viable after synchronization with either nocodazole or the anti
      tumor drug Paclitaxel (taxol) and have an abbreviated G1 phase of only 2.5-3 h
      that is significantly shorter than in somatic cells. Molecular analyses using
      quantitative RT-PCR demonstrate that human ES cells and somatic cells express
      similar cell cycle markers. However, among cyclins and cyclin-dependent kinases
      (CDKs), we observed high mRNA levels for the G1-related CDK4 and cyclin D2 genes.
      We conclude that human ES cells exhibit unique G1 cell cycle kinetics and use
      CDK4/cyclin D2 related mechanisms to attain competency for DNA replication.

PMID- 16972249
TI  - Inhibition of PPARgamma prevents type I diabetic bone marrow adiposity but not
      bone loss.
AB  - Diabetes type I is associated with bone loss and increased bone adiposity.
      Osteoblasts and adipocytes are both derived from mesenchymal stem cells located
      in the bone marrow, therefore we hypothesized that if we could block adipocyte
      differentiation we might prevent bone loss in diabetic mice. Control and insulin
      deficient diabetic BALB/c mice were chronically treated with a peroxisomal
      proliferator-activated receptor gamma (PPARgamma) antagonist, bisphenol-A
      diglycidyl ether (BADGE), to block adipocyte differentiation. Effects on bone
      density, adiposity, and gene expression were measured. BADGE treatment did not
      prevent diabetes-associated hyperglycemia or weight loss, but did prevent
      diabetes-induced hyperlipidemia and effectively blocked diabetes type I-induced
      bone adiposity. Despite this, BADGE treatment did not prevent diabetes type I
      suppression of osteoblast markers (runx2 and osteocalcin) and bone loss (as
      determined by micro-computed tomography). BADGE did not suppress osteoblast gene
      expression or bone mineral density in control mice, however, chronic (but not
      acute) BADGE treatment did suppress osteocalcin expression in osteoblasts in
      vitro. Taken together, our findings suggest that BADGE treatment is an effective
      approach to reduce serum triglyceride and free fatty acid levels as well as bone
      adiposity associated with type I diabetes. The inability of BADGE treatment to
      prevent bone loss in diabetic mice suggests that marrow adiposity is not linked
      to bone density status in type I diabetes, but we cannot exclude the possibility
      of additional BADGE effects on osteoblasts or other bone cells, which could
      contribute to preventing the rescue of the bone phenotype.

PMID- 16972250
TI  - Peroxisome proliferator-activated receptor (PPAR)gamma is expressed by human
      spermatozoa: its potential role on the sperm physiology.
AB  - The peroxisome proliferation-activated receptor gamma (PPARgamma) is mainly
      expressed in the adipose tissue and integrates the control of energy, lipid, and
      glucose homeostasis. The present study, by means of RT-PCR, Western blot, and
      immunofluorescence techniques, demonstrates that human sperm express the
      PPARgamma. The functionality of the receptor was evidenced by 15-deoxy-12,14
      prostaglandin J(2) (PGJ2) and rosiglitazone (BRL) PPARgamma-agonists that were
      tested on capacitation, acrosome reaction, and motility. Both treatments also
      increase AKT phosphorylations and influence glucose and lipid metabolism in
      sperm. The specificity of PGJ2 and BRL effects through PPARgamma on human sperm
      was confirmed by an irreversible PPARgamma antagonist, GW9662. Our findings
      provide evidence that human sperm express a functional PPARgamma whose activation
      influences sperm physiology. In conclusion, the presence of PPARgamma in male
      gamete broadens the field of action of this nuclear receptor, bringing us to look
      towards sperm as an endocrine mobile unit independent of the systemic regulation.

PMID- 16972251
TI  - Extended passaging, but not aldehyde dehydrogenase activity, increases the
      chondrogenic potential of human adipose-derived adult stem cells.
AB  - Adipose-derived adult stem (ADAS) cells represent an abundant population of
      multipotent mesodermal cells residing in various adipose tissue depots. ADAS cell
      preparations appear heterogeneous, yet at a clonal level, greater than 50% of
      these cells exhibit multilineage differentiation potential. To date, there have
      been few attempts to define prospectively a homogenous population of multipotent
      cells. In this study, we investigated whether aldehyde dehydrogenase (ALDH) can
      be used to enrich ADAS cells with increased chondrogenic potential. ALDH has been
      previously used to isolate primitive hematopoietic progenitors and has been
      implicated in early neurogenesis. Human ADAS cells were purified based on ALDH
      activity, and the cells were expanded and induced for chondrogenic
      differentiation using BMP-6 in a 3-D alginate culture. No significant differences
      in chondrogenic potential were observed in the ALDH-positive cells compared to
      unsorted controls. In contrast, significant differences were noted between cells
      assayed at passage 4 (P4) and cells assayed at passage 9 (P9). Following BMP-6
      induction, AGC1 gene expression in P9 cells increased 290-fold over P4 cells.
      Similarly, COL2A1 expression in P9 cells increased fivefold compared to P4 cells,
      while COL10A1 levels remained unchanged. Immunohistochemical analysis over 28
      days revealed consistent findings at the protein level for collagen II, collagen
      X, and aggrecan. No changes in telomerase activity were detected across passage,
      suggesting that ADAS cells retain some level of "stemness" in monolayer culture.
      These findings suggest that the chondrogenic potential of ADAS cells increases
      with passage number, although ALDH may not be a suitable marker for
      chondrogenesis.

PMID- 16972252
TI  - Hypocalcemic choreoathetosis and tetany after bisphosphonate treatment.

PMID- 16972253
TI  - Reduction of p66Shc suppresses oxidative damage in retinal pigmented epithelial
      cells and retina.
AB  - The largest isoform of the Shc adapter protein, p66Shc, has been implicated in
      oxidative damage-induced apoptosis in vital organs, because mice deficient in
      p66Shc have a 30% increase in life span and are resistant to the lethal effects
      of systemically administered paraquat, a source of severe oxidative damage. In
      this study, we utilized siRNA directed against the CH2 domain of Shc, to reduce
      p66Shc, but not p52Shc nor p46Shc in retinal pigmented epithelial (RPE) cells.
      RPE cells deficient in p66Shc had reduced susceptibility to oxidative stress
      induced apoptosis. Compared to control cells, those with reduced p66Shc had
      increased basal and oxidative stress-induced NF-kappaB transcriptional activity,
      increased levels of antioxidant enzymes, and less generation of reactive oxygen
      species when challenged with H(2)O(2). The increase in oxidative stress-induced
      NF-kappaB activity was mediated by activation of ERK. Compared to eyes injected
      with GFP siRNA, those injected with p66Shc siRNA showed less loss of retinal
      function as assessed by electroretinograms from paraquat-induced oxidative
      stress. These data suggest that p66Shc and molecular signals involved in its
      regulation provide therapeutic targets for retinal degenerations in which
      oxidative-damage plays a major role, including age-related macular degeneration
      and cone cell death in retinitis pigmentosa.

PMID- 16972254
TI  - Signaling pathways of LIGHT induced macrophage migration and vascular smooth
      muscle cell proliferation.
AB  - The biological actions of LIGHT, a member of the tumor necrosis factor
      superfamily, are mediated by the interaction with lymphotoxin-beta receptor
      (LTbetaR) and/or herpes virus entry mediator (HVEM). Previous study demonstrated
      high-level expressions of LIGHT and HVEM receptors in atherosclerotic plaques. To
      investigate the role of LIGHT in the functioning of macrophages and vascular
      smooth muscle cells (VSMC) in relation to atherogenesis, we determined the
      effects of LIGHT on macrophage migration and VSMC proliferation. We found LIGHT
      through HVEM activation can induce both events. LIGHT-induced macrophage
      migration was associated with activation of signaling kinases, including MAPKs,
      PI3K/Akt, NF-kappaB, Src members, and FAK. Proliferation of VSMC was also shown
      relating to the activation of MAPKs, PI3K/Akt, and NF-kappaB, which consequently
      led to alter the expression of cell cycle regulatory molecules. Down-regulation
      of p21, p27, and p53, and inversely up-regulation of cyclin D and RB hyper
      phosphorylation were demonstrated. In conclusion, LIGHT acts as a novel mediator
      for macrophage migration and VSMC proliferation, suggesting its involvement in
      the atherogenesis.

PMID- 16972255
TI  - Ultraviolet B-induced matrix metalloproteinase-1 and -3 secretions are mediated
      via PTEN/Akt pathway in human dermal fibroblasts.
AB  - Matrix Metalloproteinases (MMPs) are crucial enzymes for ultraviolet irradiation
      induced photoaging in human skin. Ultraviolet B (UVB) stimulates dermal
      fibroblasts to increase MMP-1 and -3 expression and extracellular matrix (ECM)
      degradation in photoaging. We investigated whether phosphatase and tensin homolog
      (PTEN)/Akt pathway is involved in secretions of MMP-1 and -3 in human dermal
      fibroblasts. The increase in MMP-1 and -3 expression and secretion occurred along
      with the increase in PTEN and Akt phosphorylation by UVB irradiation in a dose-
      and time-dependent manner. However, treatment with a casein kinase 2 inhibitor,
      5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole, inhibited their
      phosphorylations and MMP-1 and -3 secretions. Transfection of wild-type PTEN (Wt
      PTEN) decreased basal and UVB-induced MMP-1 and -3 secretions, as well as
      activator protein-1 (AP-1) activity, while transfection of small interference RNA
      of PTEN (siRNA-PTEN), phosphatase-inactive PTEN (C124S-PTEN), or lipid
      phosphatase-inactive PTEN (G129E-PTEN) increased basal or UVB-induced MMP-1 and 
      3 secretions and AP-1 activity. Transfection of constitutively active Akt (Myr
      Akt) also increased basal or UVB-induced MMP-1 and -3 secretions, as well as AP-1
      activity. However, transfection of kinase-inactive Akt (K179M-Akt) decreased
      their secretions, but showed no significant change of AP-1 activity without UVB
      irradiation, and a significant increase of AP-1 activity with UVB irradiation.
      Treatment with the phosphatidylinositol 3-kinase inhibitors, LY294002 or
      wortmannin, downregulated basal and UVB-induced MMP-1 and -3 secretions. In
      conclusion, UVB irradiation increases PTEN and Akt phosphorylation in human
      dermal fibroblasts, and these inhibition of PTEN and activation of Akt by
      phosphorylation are involved in UVB-induced MMP-1 and -3 secretions partly
      through upregulation of AP-1 activity.

PMID- 16972256
TI  - Active caspase-3 is required for osteoclast differentiation.
AB  - Based on our earlier observation that caspase-3 is present in osteoclasts that
      are not undergoing apoptosis, we investigated the role of this protein in the
      differentiation of primary osteoclasts and RAW264.7 cells (Szymczyk KH, et al.,
      2005, Caspase-3 activity is necessary for RANKL-induced osteoclast
      differentiation. The Proceedings of the 8th ICCBMT). We noted that osteoclast
      numbers are decreased in long bones of procaspase-3 knockout mice and that
      receptor activator of NF-kappaB ligand (RANKL) does not promote differentiation
      of isolated preosteoclasts. In addition, after treatment with inhibitors of
      caspase-3 activity, neither the wild-type primary nor the RAW264.7 cells express
      TRAP or became multinucleated. We found that immediately following RANKL
      treatment, procaspase-3 is cleaved and the activated protein is localized to
      lipid regions of the plasma membrane and the cytosol. We developed RAW264.7
      procaspase-3 knockdown clonal cell lines using RNAi technology. Again, treatment
      with RANKL fails to induce TRAP activity or multinucleation. Finally, we
      evaluated NF-kappaB in procaspase-3 silenced cells. We found that RANKL treatment
      prevented activation and nuclear translocation of NF-kappaB. Together these
      findings provide direct support for the hypothesis that caspase-3 activity is
      required for osteoclast differentiation.

PMID- 16972257
TI  - Prolonged absence of myostatin reduces sarcopenia.
AB  - Sarcopenia is a progressive age-related loss of skeletal muscle mass and
      strength. Parabiotic experiments show that circulating factors positively
      influence the proliferation and regenerative capacity of satellite cells in aged
      mice. In addition, we believe that negative regulators of muscle mass also serve
      to balance the signals that influence satellite cell activation and regeneration
      capacity with ageing. Myostatin, a negative regulator of pre- and postnatal
      myogenesis, inhibits satellite cell activation and muscle regeneration
      postnatally. To investigate the role of myostatin during age-related sarcopenia,
      we examined muscle mass and regeneration in young and old myostatin-null mice.
      Young myostatin-null muscle fibers were characterized by massive hypertrophy and
      hyperplasia and an increase in type IIB fibers, resulting in a more glycolytic
      muscle. With ageing, wild-type muscle became increasingly oxidative and fiber
      atrophy was prominent. In contrast no fiber type switching was observed and
      atrophy was minimal in aged myostatin-null muscle. The effect of ageing on
      satellite cell numbers appeared minimal, however, satellite cell activation
      declined significantly in both wild-type and myostatin-null muscles. In young
      mice, lack of myostatin resulted in increased satellite cell number and
      activation compared to wild-type, suggesting a greater propensity to undergo
      myogenesis, a difference maintained in the aged mice. In addition, muscle
      regeneration of myostatin-null muscle following notexin injury was accelerated
      and fiber hypertrophy and type were recovered with regeneration, unlike in wild
      type muscle. In conclusion, a lack of myostatin appears to reduce age-related
      sarcopenia and loss of muscle regenerative capacity.

PMID- 16972258
TI  - N-(4-hydroxyphenyl)retinamide induces apoptosis in human retinal pigment
      epithelial cells: retinoic acid receptors regulate apoptosis, reactive oxygen
      species generation, and the expression of heme oxygenase-1 and Gadd153.
AB  - N-(4-hydroxyphenyl)retinamide (4HPR, fenretinide), a retinoic acid (RA)
      derivative and a potential cancer preventive agent, is known to exert its
      chemotherapeutic effects in cancer cells through induction of apoptosis. Earlier
      work from our laboratory has shown that relatively low concentrations of 4HPR
      induce neuronal differentiation of cultured human retinal pigment epithelial
      (ARPE-19) cells (Chen et al., 2003, J Neurochem 84:972-981). However, at higher
      concentrations of 4HPR, these cells showed morphological changes including cell
      shrinkage and cell death. Here we demonstrate that ARPE-19 cells treated with
      4HPR exhibit a dose- and time-dependent induction of apoptosis as evidenced by
      morphological changes, mono- and oligonucleosome generation, and increased
      activity of caspases 2 and 3. The 4HPR-induced apoptosis as well as the
      activation of caspases 2 and 3 were blocked by both retinoic acid receptors (RAR)
      pan-antagonists, AGN193109 and AGN194310, and by an RARalpha-specific antagonist
      AGN194301. 4HPR treatment also increased reactive oxygen species (ROS) generation
      in ARPE-19 cells in a time-dependent manner as determined from the oxidation of
      2',7'-dichlorofluorescin. In addition, the increase in the expression of heme
      oxygenase-1 (HO-1), a stress response protein, and the growth arrest and DNA
      damage-inducible transcription factor 153 (Gadd153) in response to the ROS
      generation were also blocked by these receptor antagonists. Pyrrolidine
      dithiocarbamate (PDTC), a free-radical scavenger, inhibited 4HPR-induced ROS
      generation, the expression of its downstream mediator, Gadd153, and apoptosis in
      the pretreated cells. Therefore, our results, clearly demonstrate that 4HPR
      induces apoptosis in ARPE-19 cells and that RARs mediate this process by
      regulating ROS generation as well as the expression of Gadd153 and HO-1.

PMID- 16972259
TI  - Alterations in intranuclear localization of Runx2 affect biological activity.
AB  - The transcription factor Runx2 controls osteoblast proliferation and
      differentiation. Runx2 organizes and assembles gene-regulatory complexes in
      nuclear microenvironments where target genes are activated or suppressed in a
      context-dependent manner. Intranuclear localization of Runx2 is mediated by the
      nuclear matrix-targeting signal (NMTS), an autonomous motif with a loop (L1)-turn
      loop (L2) structure that forms predicted protein-protein interaction surfaces.
      Here we examined the functional consequences of introducing mutations in the L1
      and L2 loops of the NMTS. These mutant proteins enter the nucleus, interact with
      the hetero-dimeric partner Cbfbeta, and bind to DNA in vitro and in vivo. In
      addition, these mutants retain interaction with the carboxy-terminus interacting
      co-regulatory proteins that include TLE, YAP, and Smads. However, two critical
      mutations in the L2 domain of the NMTS decrease association of Runx2 with the
      nuclear matrix. These subnuclear targeting defective (STD) mutants of Runx2
      compromise target gene activation or repression. The biological significance of
      these findings is reflected by decreased osteogenic differentiation of
      mesenchymal progenitors, concomitant with major changes in gene expression
      profiles, upon expression of the STD Runx2 mutant. Our results demonstrate that
      fidelity of temporal and spatial localization of Runx2 within the nucleus is
      functionally linked with biological activity.

PMID- 16972260
TI  - Homocysteine-induced myofibroblast differentiation in mouse aortic endothelial
      cells.
AB  - Differentiation of myofibroblast, as evidenced by alpha-smooth muscle actin
      (alpha-SMA) expression, is largely mediated by transforming growth factor-beta1
      (TGF-beta1). This mechanism often follows inflammatory events such as endothelial
      damage due to oxidative stress, which can further leads to vascular thickening,
      stiffness, and fibrosis. We hypothesized that hyperhomocysteinemia (HHcy)-induced
      oxidative stress lead to vascular stiffness, in part due to endothelial
      myofibroblast differentiation and alteration of collagen homeostasis in the
      extracellular matrix (ECM). We tested our hypothesis in vitro using mouse aortic
      endothelial cells (MAEC). Our result shows that Hcy induces alpha-SMA and
      collagen type-1 expression in MAEC as evidenced by immunoblot and confocal
      imaging. RT-PCR shows robust increase of alpha-SMA and collagen type-1 mRNA level
      in Hcy-induced condition. We demonstrated that Hcy induces autophosphorylation of
      focal adhesion kinase (FAK) (a member of the protein tyrosine kinase (PTK)
      family) at Tyr-397. PP2 (general PTK inhibitor) as well as FAK siRNA abrogates
      Hcy-mediated alpha-SMA formation. In addition to that, Hcy-mediated TGF-beta1
      induction was inhibited by TGF-beta R1 kinase inhibitor II (ALK5 inhibitor II)
      and attenuated FAK phosphorylation and alpha-SMA expression. Furthermore, we
      showed that Hcy activates ERK-44/42 (extracellular signal-regulated kinase)
      pathway and augments collagen type-1 deposition. Studies with pharmacological ERK
      blocker, PD98059 and ERK siRNA attenuated ERK-44/42 phosphorylation and collagen
      type-1 synthesis. Taken together our results demonstrate that Hcy-mediated TGF
      beta1 upregulation triggers endothelial-myofibroblast differentiation secondary
      to FAK phosphorylation and that Hcy-induced ERK activation is involved in ECM
      remodeling by altering collagen type-1 homeostasis.

PMID- 16972261
TI  - Pharmacologic inhibitors of extracellular signal-regulated kinase (ERKs) and c
      Jun NH(2)-terminal kinase (JNK) decrease glutathione content and sensitize human
      promonocytic leukemia cells to arsenic trioxide-induced apoptosis.
AB  - Treatment with 1-4 microM As(2)O(3) slightly induced apoptosis in U-937 human
      promonocitic leukemia cells. This effect was potentiated by co-treatment with
      MEK/ERK (PD98059, U0126) and JNK (SP600125, AS601245) inhibitors, but not with
      p38 (SB203580, SB220025) inhibitors. However, no potentiation was obtained using
      lonidamine, doxorubicin, or cisplatin instead of As(2)O(3). Apoptosis
      potentiation by mitogen-activated protein kinase (MAPK) inhibitors involved both
      the intrinsic and extrinsic executionary pathways, as demonstrated by Bax
      activation and cytochrome c release from mitochondria, and by caspase-8
      activation and Bid cleavage, respectively; and the activation of both pathways
      was prevented by Bcl-2 over-expression. Treatment with MEK/ERK and JNK
      inhibitors, but not with p38 inhibitors, caused intracellular glutathione (GSH)
      depletion, which was differentially regulated. Thus, while it was prevented by N
      acetyl-L-cysteine (NAC) in the case of U0126, it behaved as a NAC-insensitive
      process, regulated at the level of DL-buthionine-(S,R)-sulfoximine (BSO)
      sensitive enzyme activity, in the case of SP600125. The MEK/ERK inhibitor also
      potentiated apoptosis and decreased GSH content in As(2)O(3)-treated NB4 human
      acute promyelocytic leukemia (APL) cells, but none of these effects were produced
      by the JNK inhibitor. MEK/ERK and JNK inhibitors did not apparently affect
      As(2)O(3) transport activity, as measured by intracellular arsenic accumulation.
      SP600126 greatly induced reactive oxygen species (ROS) accumulation, while BSO
      and U0126 had little or null effects. These results, which indicate that
      glutathione is a target of MAP kinases in myeloid leukemia cells, might be
      exploited to improve the antitumor properties of As(2)O(3), and provide a
      rationale for the use of kinase inhibitors as therapeutic agents.

PMID- 16972262
TI  - An early but intense cytokine production within the islets may be predictive for
      type 1 diabetes occurrence in the Bio Breeding (BB) rat.
AB  - The Bio Breeding (BB) rat is a useful animal model of type 1 autoimmune diabetes.
      The aim of this study was to observe and follow the cytokine and antigenic
      expressions within the islets of Langerhans in young non-diabetic, in pre
      diabetic hyperglycemic, and in overtly diabetic animals. BB rats were therefore
      checked at day 21 up to day 90 of life for blood glucose, insulin levels, degree
      of islet infiltration, expression of proinflammatory and protective cytokines and
      antibodies including CD4, CD8, CD25, LFA-1, and ICAM-1. Animals were treated with
      insulin as they became diabetic. We found that islets of non-diabetic BB rats
      became positive to both IL-1beta and IL-4 very early on, confirming a local but
      intense production of both cytokines within the islets during the initial non
      diabetic period. In addition, we observed that the production of these
      interleukins together with the expression levels of CD4 and CD25 are events
      predictive for type 1 diabetes onset in non-diabetic BB rats, as for non-obese
      diabetic (NOD) mice. In particular, the production of IL-1beta and IL-4 during
      the non-diabetic period together with the lack of enhancement of CD4 and CD25,
      indicating selective recruitment of activated T cells, may explain the failure of
      anti-diabetic treatments in this animal model of type 1 diabetes.

PMID- 16972263
TI  - Clinical characteristics of paroxysmal nonkinesigenic dyskinesia in Serbian
      family with Myofibrillogenesis regulator 1 gene mutation.
AB  - The aim of this study was to describe the clinical features of a large Serbian
      family with paroxysmal nonkinesigenic dyskinesia (PNKD) and one of the two
      previously described mutations in the Myofibrillogenesis regulator 1 gene (MR-1),
      which causes an alanine-to-valine substitution at position 9. In 5 examined out
      of 12 affected family members, attacks of dyskinesias appeared in the first 6
      months of life. Both frequency and severity of attacks showed an age-dependent
      incremental-decremental pattern with a peak between 13 to 15 years of age. They
      were frequently precipitated by stress, caffeine, fever, hunger, tiredness, as
      well as abrupt changes in temperature. Three of our patients differentiated two
      types of attacks: mild (120-180 minutes), with a predominance of functionally
      insignificant choreoathetoid movements, and severe ( approximately 15-30
      minutes), characterized by disabling dystonic and choreic movements of the
      extremities, trunk, and face. Sleep was the most reliable factor to discontinue
      an attack. This Serbian family further demonstrates that recurrent MR-1 mutations
      are associated with PNKD worldwide, which will affect genetic testing.

PMID- 16972264
TI  - Rap1 and p38 MAPK mediate 8-chloro-cAMP-induced growth inhibition in mouse
      fibroblast DT cells.
AB  - 8-Cl-cAMP, which is known to induce differentiation, growth inhibition, and
      apoptosis in various cancer cells, has been investigated as a putative anti
      cancer drug. Previously, we reported that 8-Cl-cAMP and its metabolite 8-Cl
      adenosine induce growth inhibition and apoptosis through p38 mitogen-activated
      protein kinase (MAPK) activation. To further investigate the signal mechanisms
      that regulate the cellular effects of 8-Cl-cAMP, we focused on a small GTPase
      Rap1 that is known to be involved in growth inhibition and reverse
      transformation. 8-Cl-cAMP and 8-Cl-adenosine could increase Rap1 activity, which
      was blocked by ABT702-an adenosine kinase inhibitor. This suggests that 8-Cl-cAMP
      induced Rap1 activation is also dependent on the metabolic degradation of 8-Cl
      cAMP. Overexpression of a constitutively active mutant form of Rap1 (Rap1V12)
      attenuated cellular growth and soft-agar colony formation, which was basically
      the same effect as that observed with the 8-Cl-cAMP treatment. Furthermore, the
      Rap1V12 transfectant showed a high level of p38 MAPK activation. However, 8-Cl
      cAMP-induced Rap1 activation was not diminished by SB203580, a p38 MAPK
      inhibitor, suggesting that Rap1 activation might act upstream of p38 MAPK
      activation during 8-Cl-cAMP-induced growth inhibition.

PMID- 16972265
TI  - Signaling networks from Gbeta1 subunit to transcription factors and actin
      remodeling via a membrane-located ERbeta-related protein in the rapid action of
      daidzein in osteoblasts.
AB  - Although estrogen replacement has been the main therapy to prevent and treat
      osteoporosis, there are concerns about its safety. Phytoestrogens have attracted
      attention to their potential impacts in osteoporosis prevention and treatment.
      Among phytoestrogens, the isoflavone daidzein (Dz) acts on transcription via the
      intracellular estrogen receptors (ER), mainly ERbeta, in osteoblasts, but mimics
      only part of the estrogen effects. Since estradiol also exerts rapid effects in
      osteoblasts, we investigated the multistep processes involved in the rapid
      actions of low (1-100 pM) doses of daidzein. Dz bound to a membrane moiety,
      related to ERbeta since the calcium response to Dz was blocked by an anti-ERbeta
      antibody directed against the C-terminus, but not by a double-stranded siRNA
      specific for ERbeta. This protein was coupled to a pertussis toxin (PTX)
      sensitive Gbeta1 subunit whose transducer was PLC-beta2, which triggered a rapid
      (5 sec) mobilization of calcium from the endoplasmic reticulum. Dz phosphorylated
      within 15 sec ERK1/2 whose phosphorylation involved two routes: Gbeta1/PLC
      beta2/PKC/c-Raf-1/MEK1/2 and Gbeta1/PI3K/cSrc/c-Raf-1/MEK1/2 as shown using
      several inhibitors. Dz induced rapid (1 min) changes in the actin cytoskeleton
      via the two routes. The rapid (20 sec) phosphorylation of Elk-1 and CREB by Dz
      involved Gbeta1 and ERK1/2. All the processes were insensitive to the estradiol
      antagonist ICI 182,780. In conclusion, the rapid effects of Dz seem to be
      biologically relevant for the function of osteoblast in bone since the isoflavone
      activates transcription factors linked to early genes controlling cellular
      proliferation and differentiation, and modulates actin cytoskeleton which
      controls cell adhesion, division, or secretion.

PMID- 16972266
TI  - Extracellular adenosine triphosphate protects oxidative stress-induced increase
      of p21(WAF1/Cip1) and p27(Kip1) expression in primary cultured renal proximal
      tubule cells: role of PI3K and Akt signaling.
AB  - Oxidative stress, the result of cellular production of reactive oxygen species
      (ROS), has been implicated in causing many renal diseases. Adenosine triphosphate
      (ATP) is an important extracellular signal in the regulation of many
      intracellular processes in normal tubular cells as well as in the pathogenesis of
      cell injury. This study investigated the effect of ATP on H(2)O(2)-induced
      increase of cyclin kinase inhibitors (CKI) expression and its related signal
      molecules in primary cultured renal proximal tubule cells (PTCs). H(2)O(2)
      inhibited DNA synthesis in a concentration- (>50 microM) and time-dependent
      manner (>2 h), as determined by thymidine and BrdU incorporation, and by increase
      in the p21(WAF/Cip1) and p27(Kip1) expression levels. In contrast, ATP increased
      the level of thymidine, BrdU incorporation (>10(-5) M), and decreased the
      p21(WAF/Cip1) and p27(Kip1) expression levels, suggesting that ATP has a
      protective effect against H(2)O(2)-induced oxidative damage. Suramin, reactive
      blue 2 (RB-2), MRS 2159, and MRS 2179 did block the reversing effect of ATP. In
      addition, AMP-CPP or 2-methylthio-ATP blocked H(2)O(2)-induced inhibition of DNA
      synthesis, suggesting all these P2 purinoceptors may be potentially involved. ATP
      induced stimulation of DNA synthesis was blocked by phosphatidylinositol 3-kinase
      (PI3K) and Akt inhibitors. These results suggest the involvement of P2
      purinoceptors-mediated PI3K/Akt signal pathway in the protective effect of ATP
      against H(2)O(2)-induced oxidative damage. Indeed, pre-treatment with PI3K or Akt
      inhibitors did not protect H(2)O(2)-induced lipid peroxide (LPO) production and
      inhibition of thymidine incorporation. In conclusion, ATP, in part, blocked
      H(2)O(2)-induced increase of p21(WAF1/Cip1) and p27(Kip1) expression through PI3K
      and Akt signal pathway in renal PTCs.

PMID- 16972267
TI  - Blood vessels and desmin control the positioning of nuclei in skeletal muscle
      fibers.
AB  - Skeletal muscle fibers contain hundreds to thousands of nuclei which lie
      immediately under the plasmalemma and are spaced out along the fiber, except for
      a small cluster of specialized nuclei at the neuromuscular junction. How the
      nuclei attain their positions along the fiber is not understood. Here we show
      that the nuclei are preferentially localized near blood vessels (BV),
      particularly in slow-twitch, oxidative fibers. Thus, in rat soleus muscle fibers,
      81% of the nuclei appear next to BV. Lack of desmin markedly perturbs the
      distribution of nuclei along the fibers but does not prevent their close
      association with BV. Consistent with a role for desmin in the spacing of nuclei,
      we show that denervation affects the organization of desmin filaments as well as
      the distribution of nuclei. During chronic stimulation of denervated muscles, new
      BV form, along which muscle nuclei align themselves. We conclude that the
      positioning of nuclei along muscle fibers is plastic and that BV and desmin
      intermediate filaments each play a distinct role in the control of this
      positioning.

PMID- 16972268
TI  - Pathological gambling in Parkinson's disease improves on chronic subthalamic
      nucleus stimulation.
AB  - Pathological gambling (PG) related to dopaminergic treatment in Parkinson's
      disease (PD) is part of a spectrum of behavioral disorders called the dopamine
      dysregulation syndrome (DDS). We describe a series of PD patients with
      preoperative active PG due to dopaminergic treatment from a total of 598 patients
      who have undergone surgery for subthalamic nucleus stimulation for disabling
      motor fluctuations. The patients had systematic open assessment of behavioral
      symptoms and standardized assessments of motor symptoms, mood, and apathy. Seven
      patients (6 men, 1 woman; age, 54 +/- 9 years; levodopa equivalent dose, 1,390 +/
      350 mg/day) had preoperative PG over a mean of 7 years, intolerant to reduction
      in medication. Six had nonmotor fluctuations and four had other behavioral
      symptoms consistent with a diagnosis of the DDS. After surgery, motor symptoms
      improved, allowing for 74% reduction of dopaminergic treatment, below the dosage
      of gambling onset. In all patients, PG resolved postoperatively after 18 months
      on average (range, 0-48), although transient worsening occurred in two.
      Improvement paralleled the time course and degree of reduction in dopaminergic
      treatment. Nonmotor fluctuations, off period dysphoria, and other symptoms of the
      DDS improved. Two patients developed persistent apathy. In conclusion, PG and
      other symptoms of the DDS-associated dopaminergic treatment improved in our
      patients following surgery. Dopaminergic dysregulation commonly attributed to
      pulsatile overstimulation of the limbic dopaminergic system may be subject to
      desensitization on chronic subthalamic stimulation, which has a relative motor
      selectivity and allows for decrease in dopaminergic treatment.

PMID- 16972271
TI  - Long-term loading inhibits ERK1/2 phosphorylation and increases FGFR3 expression
      in MC3T3-E1 osteoblast cells.
AB  - Bone tissue homeostasis relies upon the ability of cells to detect and interpret
      extracellular signals that direct changes in tissue architecture. This study
      utilized a four-point bending model to create both fluid shear and strain forces
      (loading) during the time-dependent progression of MC3T3-E1 preosteoblasts along
      the osteogenic lineage. Loading was shown to increase cell number, alkaline
      phosphatase (ALP) activity, collagen synthesis, and the mRNA expression levels of
      Runx2, osteocalcin (OC), osteopontin, and cyclo-oxygenase-2. However,
      mineralization in these cultures was inhibited, despite an increase in calcium
      accumulation, suggesting that loading may inhibit mineralization in order to
      increase matrix deposition. Loading also increased fibroblast growth factor
      receptor-3 (FGFR3) expression coincident with an inhibition of FGFR1, FGFR4,
      FGF1, and extracellular signal-related kinase (ERK)1/2 phosphorylation. To
      examine whether these loading-induced changes in cell phenotype and FGFR
      expression could be attributed to the inhibition of ERK1/2 phosphorylation, cells
      were grown for 25 days in the presence of the MEK1/2 inhibitor, U0126.
      Significant increases in the expression of FGFR3, ALP, and OC were observed, as
      well as the inhibition of FGFR1, FGFR4, and FGF1. However, U0126 also increased
      matrix mineralization, demonstrating that inhibition of ERK1/2 phosphorylation
      cannot fully account for the changes observed in response to loading. In
      conclusion, this study demonstrates that preosteoblasts are mechanoresponsive,
      and that long-term loading, whilst increasing proliferation and differentiation
      of preosteoblasts, inhibits matrix mineralization. In addition, the increase in
      FGFR3 expression suggests that it may have a role in osteoblast differentiation.

PMID- 16972272
TI  - Corticotropin-releasing factor (CRF) receptor type 2 in the human stomach:
      protective biological role by inhibition of apoptosis.
AB  - Corticotropin-releasing factor agonists exert inhibitory effects in stomach
      functions possibly through peripheral routes. We have previously reported the
      expression of Urocortin (Ucn) I, an endogenous ligand of both CRF receptor types
      CRF(1) and CRF(2), in the human stomach. We examined CRF(1) and CRF(2) expression
      in the same tissue. Using RT-PCR, CRF(2) but not CRF(1) transcripts were detected
      in RNA extracts from normal human stomach. In addition, immunohistochemical
      analysis revealed receptor protein in epithelial gastric cells. In order to
      investigate the biological role of CRF(2) in these cells, an in vitro model was
      established, using the gastric cancer cell line AGS transiently transfected to
      express functional CRF(2). The effect of the CRF(2) endogenous ligands CRF, Ucns
      I and II on the growth parameters of the AGS/CRF(2) was examined. After 1 day of
      exposure, all three ligands reduced the degree of apoptosis (16%-19%, n = 9, P <
      0.05) compared to non-treated controls and this effect was observed for 3 days of
      treatment. No such effect was detected in non-transfected cells, suggesting
      mediation through CRF(2) receptors. Administration of CRF, Ucns I and II had no
      effect on the proliferation rate of AGS/CRF(2) cells or on the release of PGE(2)
      by them. Our results demonstrate CRF(2) expression in the human gastric mucosa
      and indicate a physiological role of this receptor type in regulating apoptosis,
      an important parameter of gastric cell regeneration. Paracrine effects exerted by
      locally expressed endogenous ligands, such as Ucn I, support a significant role
      of the peripheral CRF system in gastric physiology. J. Cell. Physiol. 209: 905
      911, 2006. (c) 2006 Wiley-Liss, Inc.

PMID- 16972273
TI  - Ubiquitin-proteasome system and Parkinson's disease.
AB  - Increasing genetic, pathological, and experimental evidence suggest that
      neurodegeneration in both familial and sporadic forms of Parkinson's disease (PD)
      may be related to a defect in the capacity of the ubiquitin-proteasome system
      (UPS) to clear unwanted proteins, resulting in protein accumulation, aggregation,
      and cytotoxicity. This concept is supported by in vitro and in vivo laboratory
      experiments which show that inhibition of UPS function can cause
      neurodegeneration coupled with the formation of Lewy body-like inclusions. This
      hypothesis could account for the presence of protein aggregates and Lewy bodies
      in PD, the other biochemical features seen in the disorder, and the age-related
      vulnerability of the substantia nigra pars compacta. It also suggests novel
      targets for putative neuroprotective therapies for PD.

PMID- 16972274
TI  - Acute loss of transcription factor E2F1 induces mitochondrial biogenesis in HeLa
      cells.
AB  - Here, we sought to clarify the comprehensive cellular response to transcription
      factor E2F1 expression using short interfering RNA (siRNA)-mediated gene
      silencing to examine the roles of E2F1. For this purpose, we analyzed global gene
      expression changes in E2F1 knockdown HeLa cells, where no changes in cell growth
      or apoptosis were observed. Among the identified genes, the mRNA levels of
      mitochondria-encoded genes were highly elevated in E2F1 siRNA-treated cells, but
      not in E2F6 siRNA-treated cells, relative to control siRNA-treated cells. These
      changes were accompanied by a significant increase in the transcription and
      replication of mitochondria DNA as well as the induction of nuclear-encoded
      mitochondrial topoisomerase I (TOP1MT) mRNA in E2F1 knockdown cells, but not in
      E2F6 knockdown cells, whereas the levels of nuclear-encoded mitochondrial
      transcription factor A (TFAM) mRNA and protein were unchanged, relative to the
      levels in control siRNA-treated cells. Time-course experiments demonstrated that
      the induction of TOP1MT coincided with the timing of E2F1 loss. In addition, E2F1
      knockdown cells, but not E2F6 knockdown cells, displayed increased ATP levels
      along with an accumulation of cytochrome b protein. Finally, RNA interference
      (RNAi)-mediated reduction in E2F1 knockdown HeLa cells, but not in E2F6 knockdown
      HeLa cells, resulted in increased anticancer drug sensitivity. Taken together,
      these data demonstrate a novel physiological aspect of E2F1 in human cancer
      cells, where activated mitochondrial biogenesis occurs as a consequence of the
      acute loss of E2F1.

PMID- 16972275
TI  - When it comes to botulinum toxin, children and adults are not the same:
      multimuscle option for children with cerebral palsy.

PMID- 16972277
TI  - Disease connections: a new peer-reviewed dialog.

PMID- 16972276
TI  - Increase in body weight after pramipexole treatment in Parkinson's disease.
AB  - Body weight changes occur during the clinical course of Parkinson's disease (PD)
      and with surgical treatment, but the effect of dopaminergic treatment on weight
      is unknown. Body mass index (BMI), Hamilton depression scale score (HDS), and
      Unified Parkinson's Disease Rating Scale III (UPRS-III) were measured before and
      3 months after starting pramipexole in 28 PD patients. Pramipexole produced a
      significant weight increase, as well as motor and mood improvement (P <0.001).
      HDS and BMI changes were mildly related (P = 0.05). A direct effect of
      pramipexole on limbic D(3) receptors involved in the control of feeding may be
      responsible for weight gain in PD.

PMID- 16972279
TI  - Biology of the adult enteric neural stem cell.
AB  - An increasing body of evidence has accumulated in recent years supporting the
      existence of neural stem cells in the adult gut. There are at least three groups
      that have obtained them using different methodologies and have described them in
      vitro. There is a growing amount of knowledge on their biology, but many
      questions are yet unanswered. Among these questions is whether these cells are
      part of a permanent undifferentiated pool or are recruited in a regular basis; in
      addition, the factors and genes involved in their survival, proliferation,
      migration, and differentiation are largely unknown. Finally, with between 10 and
      20% of adults suffering from diseases involving the enteric nervous system, most
      notably irritable bowel syndrome and gastroesophageal reflux, what is the
      possible role of enteric nervous stem cells in health and disease?

PMID- 16972281
TI  - Homology modeling and molecular dynamics study of West Nile virus NS3 protease: a
      molecular basis for the catalytic activity increased by the NS2B cofactor.
AB  - The West Nile virus (WNV) NS3 serine protease, which plays an important role in
      assembly of infective virion, is an attractive target for anti-WNV drug
      development. Cofactors NS2B and NS4A increase the catalytic activity of NS3 in
      dengue virus and Hepatitis C virus, respectively. Recent studies on the WNV-NS3
      characterize the catalytically active form of NS3 by tethering the 40-residue
      cofactor NS2B. It is suggested that NS2B is essential for the NS3 activity in
      WNV, while there is no information of the WNV-NS3-related crystal structure. To
      understand the role of NS2B/substrate in the NS3 catalytic activity, we built a
      series of models: WNV-NS3 and WNV-NS3-NS2B and WNV-NS3-NS2B-substrate using
      homology modeling and molecular modeling techniques. Molecular dynamics (MD)
      simulations were performed for 2.75 ns on each model, to investigate the
      structural stabilization and catalytic triad motion of the WNV NS3 protease with
      and without NS2B/substrate. The simulations show that the NS3 rearrangement
      occurs upon the NS2B binding, resulting in the stable D75-OD1...H51-NH hydrogen
      bonding. After the substrate binds to the NS3-NS2B active site, the NS3 protease
      becomes more stable, and the catalytic triad is formed. These results provide a
      structural basis for the activation and stabilization of the enzyme by its
      cofactor and substrate.

PMID- 16972282
TI  - Structure modeling, ligand binding, and binding affinity calculation (LR-MM-PBSA)
      of human heparanase for inhibition and drug design.
AB  - Human heparanase is an endo-beta-D-glycosidase that cleaves heparan sulphate (HS)
      chains in the extracellular matrix and basement membrane. It is known that the
      cleavage of HS by heparanase results in cell invasion and metastasis of cancer.
      Therefore, heparanase is considered an important target for cancer drug
      development. The three-dimensional structure of heparanase would be useful in the
      rational design of inhibitors targeted to the enzyme; however, the three
      dimensional structure has not yet been determined. In our effort to design
      inhibitors, we developed a three-dimensional structure of heparanase using a
      homology-modeling approach. The homology-built structure is consistent to
      previous bioinformatics and site-mutation experimental results. The heparanase
      features a (alpha/beta)(8) TIM-barrel fold with two glutamate residues (Glu225
      and Glu343) located in the active-site cleft. This feature supports the putative
      mechanism of proton donor and nucleophilic sites. Docking simulations yielded 41
      complex structures, which indicate that the bound inhibitor could block ligand
      binding into the catalytic site. A free energy of binding model was established
      for 25 heparanase inhibitors with a training set of 25 heparanase inhibitors
      using the linear response MM-PBSA approach (LR-MM-PBSA). The correlation between
      calculated and experimental activity was 0.79 and the reliability of the model
      was validated with leave-one-out cross-validation method. Its predictive
      capability was further validated using a test set of 16 inhibitors similar to the
      training set of inhibitors. The correlation between the predicted and observed
      activities is significantly improved by the protein "induced-fit" that accounts
      for the flexibility of the receptor. These interaction and pharmacophore elements
      provide a unique insight to the rational design of new ligands targeted to the
      enzyme.

PMID- 16972283
TI  - Characterization and tissue-specific expression of two lepidopteran farnesyl
      diphosphate synthase homologs: implications for the biosynthesis of ethyl
      substituted juvenile hormones.
AB  - The sesquiterpenoid juvenile hormone (JH) regulates insect development and
      reproduction. Most insects produce only one chemical form of JH, but the
      Lepidoptera produce four derivatives featuring ethyl branches. The biogenesis of
      these JHs requires the synthesis of ethyl-substituted farnesyl diphosphate (FPP)
      by FPP synthase (FPPS). To determine if there exist more than one lepidopteran
      FPPS, and whether one FPPS homolog is better adapted for binding the bulkier
      ethyl-branched substrates/products, we cloned three lepidopteran FPPS cDNAs, two
      from Choristoneura fumiferana and one from Pseudaletia unipuncta. Amino acid
      sequence comparisons among these and other eukaryotic FPPSs led to the
      recognition of two lepidopteran FPPS types. Type-I FPPSs display unique active
      site substitutions, including several in and near the first aspartate-rich motif,
      whereas type-II proteins have a more "conventional" catalytic cavity. In a yeast
      assay, a Drosophila FPPS clone provided full complementation of an FPPS mutation,
      but lepidopteran FPPS clones of either type yielded only partial complementation,
      suggesting unusual catalytic features and/or requirements of these enzymes.
      Although a structural analysis of lepidopteran FPPS active sites suggested that
      type-I enzymes are better suited than type-II for generating ethyl-substituted
      products, a quantitative real-time PCR assessment of their relative abundance in
      insect tissues indicated that type-I expression is ubiquitous whereas that of
      type-II is essentially confined to the JH-producing glands, where its transcripts
      are approximately 20 times more abundant than those of type-I. These results
      suggest that type-II FPPS plays a leading role in lepidopteran JH biosynthesis in
      spite of its apparently more conventional catalytic cavity.

PMID- 16972284
TI  - Measurement of brain temperature with magnetic resonance spectroscopy in acute
      ischemic stroke.
AB  - OBJECTIVE: Pyrexia is associated with poor outcome after stroke, but the
      temperature changes in the brain after stroke are poorly understood. We used
      magnetic resonance spectroscopic imaging (water-to-N-acetylaspartate frequency
      shift) to measure cerebral temperature noninvasively in stroke patients. METHODS:
      We performed magnetic resonance diffusion, perfusion (diffusion- and perfusion
      weighted imaging), and magnetic resonance spectroscopic imaging, compared
      temperatures in tissues as defined by the diffusion-weighted imaging appearance
      (definitely abnormal, possibly abnormal and immediately adjacent normal-appearing
      brain, and normal brain), and tested associations with lesion and patient
      characteristics. RESULTS: Among 40 patients, temperature was higher in possibly
      abnormal (37.63 degrees C) than in definitely abnormal tissue (37.30 degrees C; p
      < 0.001) or in normal-appearing brain (ipsilateral, 37.16 degrees C;
      contralateral, 37.22 degrees C; both p < 0.001). Ischemic lesion temperature
      increased before normal brain temperature. Higher temperatures occurred in
      lesions that were large, had diffusion/perfusion-weighted imaging mismatch, had
      reduced cerebral blood flow, and in clinically severe strokes. Only 1 of 25
      patients with ischemic lesion temperature greater than 37.5 degrees C was
      pyrexial. INTERPRETATION: Temperature is elevated in acutely ischemic brain. More
      work is required to determine whether raised temperature results from ischemic
      metabolic reactions, impaired heat exchange from reduced cerebral blood flow, or
      early inflammatory cell activity (or a combination of these), but magnetic
      resonance spectroscopic imaging could be used in studies of temperature after
      brain injury and to monitor interventions.

PMID- 16972285
TI  - ROSETTALIGAND: protein-small molecule docking with full side-chain flexibility.
AB  - Protein-small molecule docking algorithms provide a means to model the structure
      of protein-small molecule complexes in structural detail and play an important
      role in drug development. In recent years the necessity of simulating protein
      side-chain flexibility for an accurate prediction of the protein-small molecule
      interfaces has become apparent, and an increasing number of docking algorithms
      probe different approaches to include protein flexibility. Here we describe a new
      method for docking small molecules into protein binding sites employing a Monte
      Carlo minimization procedure in which the rigid body position and orientation of
      the small molecule and the protein side-chain conformations are optimized
      simultaneously. The energy function comprises van der Waals (VDW) interactions,
      an implicit solvation model, an explicit orientation hydrogen bonding potential,
      and an electrostatics model. In an evaluation of the scoring function the
      computed energy correlated with experimental small molecule binding energy with a
      correlation coefficient of 0.63 across a diverse set of 229 protein- small
      molecule complexes. The docking method produced lowest energy models with a root
      mean square deviation (RMSD) smaller than 2 A in 71 out of 100 protein-small
      molecule crystal structure complexes (self-docking). In cross-docking
      calculations in which both protein side-chain and small molecule internal degrees
      of freedom were varied the lowest energy predictions had RMSDs less than 2 A in
      14 of 20 test cases.

PMID- 16972286
TI  - Aqueous polymer two-phase systems: effective tools for plasma membrane
      proteomics.
AB  - Plasma membranes (PMs) are of particular importance for all living cells. They
      form a selectively permeable barrier to the environment. Many essential tasks of
      PMs are carried out by their proteinaceous components, including molecular
      transport, cell-cell interactions, and signal transduction. Due to the key role
      of these proteins for cellular function, they take center-stage in basic and
      applied research. A major problem towards in-depth identification and
      characterization of PM proteins by modern proteomic approaches is their low
      abundance and immense heterogeneity in different cells. Highly selective and
      efficient purification protocols are hence essential to any PM proteome analysis.
      An effective tool for preparative isolation of PMs is partitioning in aqueous
      polymer two-phase systems. In two-phase systems, membranes are separated
      according to differences in surface properties rather than size and density.
      Despite their rare application to the fractionation of animal tissues and cells,
      they represent an attractive alternative to conventional fractionation protocols.
      Here, we review the principles of partitioning using aqueous polymer two-phase
      systems and compare aqueous polymer two-phase systems with other methods
      currently used for the isolation of PMs.

PMID- 16972287
TI  - Chemistry meets proteomics: the use of chemical tagging reactions for MS-based
      proteomics.
AB  - As proteomics matures from a purely descriptive to a function-oriented discipline
      of the life sciences, there is strong demand for novel methodologies that
      increase the depth of information that can be obtained from proteomic studies. MS
      has long played a central role for protein identification and characterization,
      often in combination with dedicated chemical modification reactions. Today,
      chemistry is helping to advance the field of proteomics in numerous ways. In this
      review, we focus on those methodologies that have a significant impact for the
      large-scale study of proteins and peptides. This includes approaches that allow
      the introduction of affinity tags for the enrichment of subclasses of peptides or
      proteins and strategies for in vitro stable isotope labeling for quantification
      purposes, among others. Particular attention is given to the study of PTMs where
      recent advancements have been promising, but many interesting targets are not yet
      being addressed.

PMID- 16972288
TI  - Proteomics as a route to identification of toxicity targets in environmental
      toxicology.
AB  - Ecotoxicology describes a three-way relationship between ecosystems, chemical
      pollutants and living organisms. It is predicated on the fact that chemical
      pollution can exert toxic effects on organisms at the individual and population
      levels. These toxic effects may provide important information to supplement
      chemical analysis of environmental samples and aid in assessing the environmental
      quality of specific ecosystems. Traditionally, effects have been detected by
      means of biomarkers which, of necessity, were often molecules or processes known
      to be affected by pollutants. Proteomics provides a means of achieving high
      throughput analysis of effects on protein populations and sub-populations with
      the potential to identify novel biomarkers. This review summarises the main
      approaches currently used in this area and assesses the potential of proteomics
      for identification of novel toxicity targets.

PMID- 16972289
TI  - Optimized synthesis of AMPA receptor antagonist ZK 187638 and neurobehavioral
      activity in a mouse model of neuronal ceroid lipofuscinosis.
AB  - Previous structure-activity relationship studies in the search for a potent,
      noncompetitive alpha-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid
      (AMPA) receptor antagonist led to 2,3-dimethyl-6-phenyl-12H-[1,3]dioxolo[4,5
      h]imidazo[1,2-c][2,3]benzodiazepine (ZK 187638). However, the first synthesis had
      some drawbacks regarding reagents, processes, and overall yield, which
      furthermore decreased when the synthesis was scaled up. Therefore, we now report
      a new synthetic route for this compound which requires fewer steps and is suited
      for large-scale production. This compound significantly relieved the symptoms of
      neuromuscular deficit in mnd mice, a model of neuronal ceroid lipofuscinosis with
      motor neuron dysfunction. After oral administration, the concentrations of the
      compound in the brain and spinal cord were about threefold higher than those in
      the plasma. In summary, this novel AMPA antagonist is accessible through an
      optimized synthetic route, has good neurobehavioral activity, oral
      bioavailability, and favorable brain penetration. This opens new possibilities
      for the treatment of devastating neurological diseases that are mediated by the
      AMPA receptor.

PMID- 16972290
TI  - Synthesis and characterization of mixed-valent manganese phosphonate cage
      complexes.
AB  - The reaction of phenylphosphonic acid (PhPO(3)H(2)) with the mixed-valent basic
      oxo-centered manganese triangle [Mn(3)O(O(2)CCMe(3))(6)(py)(3)] (1; where
      py=pyridine) in the presence of a suitable base gives four different manganese
      clusters depending on the identity of the base. The syntheses and structural
      characterization of [Mn(18)(mu(3)
      O)(8)(PhPO(3))(14)(O(2)CCMe(3))(12)(py)(6)(H(2)O)(2)] (2), [Mn(7)(mu(3)
      O)(3)(O(3)PPh)(3)(O(2)CCMe(3))(8)(py)(3)] (3), [Mn(9)Na(mu(3)-O)(4)(mu(4)
      O)(2)(O(3)PPh)(2)(O(2)CCMe(3))(12)(H(2)O)(2)(H(2)O)(0.67)(Py)(0.33)] (4), and
      [Mn(13)(mu(3)-O)(8)(OMe)(8)(O(3)PPh)(4)(O(2)CCMe(3))(10)] (5) are described.
      Complexes 4 and 5 are homovalent Mn(III) cages, while 2 and 3 contain divalent,
      trivalent, and/or tetravalent ions. All the manganese centers are valence
      localized, the octahedral Mn(III) sites being recognizable by marked Jahn-Teller
      distortions. The magnetic properties of compounds 2-5 have been investigated in
      the polycrystalline state by magnetic susceptibility and high-field magnetization
      measurements, which reveal that spin ground states vary from 0< or =S > or =8. AC
      susceptibility measurements performed on 4 and 5, in the 1.6-10.0 K ranges show
      the presence of out of AC susceptibility signal (chi(M)'') for 4, and an
      effective energy barrier (U(eff)) for the re-orientation of the magnetization is
      found to be 17 K, but for 5, the chi(M)'' maximum is found to be below 1.5 K.

PMID- 16972291
TI  - The nature of halogen...halogen synthons: crystallographic and theoretical
      studies.
AB  - A study of the halogen...halogen contacts in organic compounds using ab initio
      calculations and the results of previously reported crystallographic studies show
      that these interactions are controlled by electrostatics. These contacts can be
      represented by the geometric parameters of the C--X1...X2--C moieties (where
      theta1=C--X1...X2 and theta2=X1...X2--C; ri=X1...X2 distance). The distributions
      of the contacts within the sum of van der Waals radii (rvdW) versus thetai
      (theta1=theta2) show a maximum at theta approximately 150 degrees for X=Cl, Br,
      and I. This maximum is not seen in the distribution of F...F contacts. These
      results are in good agreement with our ab initio calculations. The theoretical
      results show that the position of the maximum depends on three factors: 1) The
      type of halogen atom, 2) the hybridization of the ipso carbon atom, and 3) the
      nature of the other atoms that are bonded to the ipso carbon atom apart from the
      halogen atom. Calculations show that the strength of these contacts decreases in
      the following order: I...I>Br...Br>Cl...Cl. Their relative strengths decrease as
      a function of the hybridization of the ipso carbon atom in the following order:
      sp2>sp>sp3. Attaching an electronegative atom to the carbon atom strengthens the
      halogen...halogen contacts. An electrostatic model is proposed based on two
      assumptions: 1) The presence of a positive electrostatic end cap on the halogen
      atom (except for fluorine) and 2) the electronic charge is anisotropically
      distributed around the halogen atom.

PMID- 16972292
TI  - Chemoenzymatic synthesis and antimicrobial and haemolytic activities of
      amphiphilic bis(phenylacetylarginine) derivatives.
AB  - Novel bis(N(alpha)-phenylacetyl-L-arginine)-alpha,omega-alkanediamide
      dihydrochloride (bis(PhAcArg)) derivatives with antimicrobial activity were
      designed and synthesised by a chemoenzymatic strategy. The new structures consist
      of two N(alpha)-phenylacetyl-L-arginine moieties connected by an alkanediamine
      spacer chain of 6, 8, 10, 12, and 14 methylene units through amide bonds. The key
      step in the chemoenzymatic strategy is the double aminolysis of the N(alpha)
      phenylacetyl-L-arginine methyl ester by the corresponding alpha,omega
      alkanediamine catalyzed by papain in ethanolic media. The compounds synthesised
      were tested as antimicrobials against 15 bacterial and 8 fungal species. The
      antimicrobial activity and selectivity depend strongly on the spacer chain
      length. The bis(PhAcArg) derivative with the spacer chain of 12 methylene groups
      gave the lowest MIC values against Gram-positive bacteria, whereas that with 14
      methylene units was the best against Gram-negative bacteria. Interestingly, these
      novel compounds showed enhanced antibacterial activity relative to the lead
      compound, bis(N(alpha)-caproyl-L-arginine)-1,3-propanediamide dihydrochloride
      (C(3)(CA)(2)), and moderate antifungal activity. Moreover, tests of haemolytic
      activity toward human erythrocytes revealed that haemolysis increases with spacer
      chain length. Importantly, the compounds were classified as not irritating to
      eyes, with the exception of the compound with the spacer chain of 14 methylene
      groups, which was a slight eye irritant.

PMID- 16972293
TI  - Radical additions of xanthates to vinyl epoxides and related derivatives: a
      powerful tool for the modular creation of quaternary centers.

PMID- 16972294
TI  - Molecular transporters: synthesis of oligoguanidinium transporters and their
      application to drug delivery and real-time imaging.

PMID- 16972295
TI  - Intercalated smectic a phases in banana-shaped liquid crystals with carbonate end
      groups.
AB  - Novel, symmetrical, bent-core mesogens, namely substituted 1,3-phenylenebis{4'
      [(ethoxycarbonyl)oxy]-1,1'-biphenyl}-4-carboxylates, are prepared with carbonate
      groups at both ends of the molecules. The mesophase properties are investigated
      for different electron-donating and -withdrawing substituents connected to the
      central ring at different positions. These compounds exhibit nematic and/or
      smectic A intercalated (SmA(int)) mesophases. Electro-optical studies show a very
      significant electric-field-induced biaxiality that is fast (<1 ms) and large
      (0.03) associated with a high birefringence (0.33 at 500 nm, 10 V mum(-1) field)
      for the unsubstituted analogue. For one substance this effect is observable from
      above 100 degrees C down to room temperature. Such electric-field-induced
      biaxiality may find practical applications in fast electro-optic modulation
      devices.

PMID- 16972296
TI  - Advances in plant proteomics.
AB  - With the avalanche of genomic information and improvements in analytical
      technology, proteomics is becoming increasingly important for the study of many
      different aspects of plant functions. Since proteins serve as important
      components of major signaling and biochemical pathways, studies at protein levels
      are essential to reveal molecular mechanisms underlying plant growth,
      development, and interactions with the environment. The plant proteome is highly
      complex and dynamic. Although great strides need to be taken towards the ultimate
      goal of characterizing all the proteins in a proteome, current technologies have
      provided immense opportunities for high-throughput proteomic studies that have
      gone beyond simple protein identification to analyzing various functional
      aspects, such as quantification, PTM, subcellular localization, and protein
      protein interactions. In this review of plant proteomics, advances in protein
      fractionation, separation, and MS will be outlined. Focus will be on recent
      development in functional analysis of plant proteins, which paves the way towards
      the comprehensive integration with transcriptomics, metabolomics, and other large
      scale "-omics" into systems biology.

PMID- 16972297
TI  - Proteomics and transfusion medicine: future perspectives.
AB  - Limited number of important discoveries have greatly contributed to the
      progresses achieved in the blood transfusion; ABO histo-blood groups, citrate as
      anticoagulant, fractionation of plasma proteins, plastic bags and apheresis
      machines. Three major types of blood products are transfused to patients: red
      cell concentrates, platelet concentrates and fresh frozen plasma. Several
      parameters of these products change during storage process and they have been
      well studied over the years. However, several aspects have completely been
      ignored; in particular those related to peptide and protein changes. This review
      presents what has been done using proteomic tools and the potentials of
      proteomics for transfusion medicine.

PMID- 16972298
TI  - Proteomics and metabolomics: the molecular make-up of toxic aromatic pollutant
      bioremediation.
AB  - Microbial-mediated attenuation of toxic aromatic pollutants offers great
      potential for the restoration of contaminated environments in an ecologically
      acceptable manner. However, incomplete biological information regarding the
      regulation of growth and metabolism in many microbial communities restricts
      progress in the site-specific mineralization process. In the postgenomic era,
      recent advances in MS have allowed enormous progress in proteomics and elucidated
      many complex biological interactions. These research forefronts are now expanding
      toward the analysis of low-molecular-weight primary and secondary metabolites
      analysis, i.e., metabolomics. The advent of 2-DE in conjunction with MS offers a
      promising approach to address the molecular mechanisms of bioremediation. The two
      fields of proteomics and metabolomics have thus far worked separately to identify
      proteins and primary and secondary metabolites during bioremediation. A
      simultaneous study combining functional proteomics and metabolomics, i.e.,
      proteometabolomics would create a system-wide approach to studying site-specific
      microorganisms during active mineralization processes. This article deals with
      advances in environmental proteomics and metabolomics and advocates the
      simultaneous study of both technologies to implement cell-free bioremediation.

PMID- 16972299
TI  - Proteomic analysis of cancer tissues: shedding light on carcinogenesis and
      possible biomarkers.
AB  - Lung, gastric, colorectal, pancreatic, and esophageal cancers, as well as
      hepatocellular carcinoma (HCC), were the six most common and highly fatal cancers
      for Japanese men in Japan in 2003, while for women uterine cervical cancer could
      also be added to this list. To identify diagnostic or therapeutic biomarkers for
      these cancers, investigators are nowadays performing proteomic analyses of cancer
      tissues and cells, and revealing a large number of molecules which are
      diagnostic, prognostic and informative of carcinogenesis. From reports of
      proteomic analyses of cancerous tissues and noncancerous tissues sampled from
      HCC, and pancreatic, esophageal, gastric, colorectal, lung and uterine cervical
      cancers, we classified the proteins into digestive enzymes, growth factors, cell
      adhesion molecules, calcium-binding proteins, proteases, protease inhibitors,
      transporter proteins, structural molecules, apoptosis inhibitor, molecular
      chaperone, as well as proteins related to cell growth, cell differentiation, cell
      transformation, tumor invasion, carcinogen metabolism, and others. The aim of
      this study was to understand carcinogenesis of major cancers from a proteomics
      perspective using samples from cancer patients, and to elucidate their tumor
      biomarkers.

PMID- 16972300
TI  - Genotyping fetal paternally inherited SNPs by MALDI-TOF MS using cell-free fetal
      DNA in maternal plasma: influence of size fractionation.
AB  - The determination of fetal point mutations from fetal cell-free DNA (cf-DNA) in
      maternal plasma is technically challenging due to the preponderance of maternal
      sequences. It has recently been shown that fetal cf-DNA sequences are smaller
      than maternal ones and that the selection of small cf-DNA fragments by size
      fractionation by agarose gel electrophoresis leads to the enrichment of fetal cf
      DNA sequences, thereby permitting the detection of otherwise masked fetal point
      mutations. In a separate development, the use of MALDI-TOF MS has also been shown
      to facilitate the detection of fetal point mutations from cf-DNA in maternal
      plasma. In this study, a combination of these approaches was examined. cf-DNA was
      extracted from 18 maternal plasma samples, 10 taken at term and 8 obtained early
      in the second trimester. A total of 41 SNP loci were examined in size
      fractionated and total cf-DNA using either a conventional homogeneous MassEXTEND
      (hME) assay or a nucleotide-specific single allele base extension reaction
      (SABER) assay. The analysis of total cf-DNA indicated that size fractionation
      considerably enhanced the sensitivity of the standard hME assay, especially for
      samples taken early in pregnancy. Size fractionation also rendered the signals
      obtained by the SABER assay more precise.

PMID- 16972301
TI  - Cytochrome c oxidase expression in chronic and intermittent hypoxia rat
      gastrocnemius muscle quantitated by CE.
AB  - We investigated the effects of hypoxia and intermittent hypoxia in rat muscle by
      quantitating the expression of genes encoding cytochrome c oxidase (CytOx)
      subunits I, II and IV, and ribosomal 12S RNA. The quantitative assessment was
      made by CE in a polymer network, laser being used to facilitate the detection of
      induced fluorescence. Constant and intermittent hypoxia influence gene expression
      and ribosomal activity to different degrees. We found constant hypoxia to be
      accompanied by an increment in the mitochondrial CytOx subunit transcripts II and
      I and 12S ribosomal subunit, whereas the nuclear subunit (IV) remained unchanged.
      No changes were observed in intermittent hypoxic rats. Despite the increment in
      messenger expression, the decrease in enzyme activity was accompanied by a
      decrease in citrate synthase activity, a marker of mitochondrial function. The
      increment in CytOx mitochondrial subunits messengers and ribosomal 12S RNA under
      prolonged chronic hypoxia could be a consequence of reduced protein synthesis
      that leads to messenger accumulation.

PMID- 16972302
TI  - A new PCR-CGE (size and color) method for simultaneous detection of genetically
      modified maize events.
AB  - We present a novel multiplex PCR assay for simultaneous detection of multiple
      transgenic events in maize. Initially, five PCR primers pairs specific to events
      Bt11, GA21, MON810, and NK603, and Zea mays L. (alcohol dehydrogenase) were
      included. The event specificity was based on amplification of transgene/plant
      genome flanking regions, i.e., the same targets as for validated real-time PCR
      assays. These short and similarly sized amplicons were selected to achieve high
      and similar amplification efficiency for all targets; however, its unambiguous
      identification was a technical challenge. We achieved a clear distinction by a
      novel CGE approach that combined the identification by size and color (CGE-SC).
      In one single step, all five targets were amplified and specifically labeled with
      three different fluorescent dyes. The assay was specific and displayed an LOD of
      0.1% of each genetically modified organism (GMO). Therefore, it was adequate to
      fulfill legal thresholds established, e.g., in the European Union. Our CGE-SC
      based strategy in combination with an adequate labeling design has the potential
      to simultaneously detect higher numbers of targets. As an example, we present the
      detection of up to eight targets in a single run. Multiplex PCR-CGE-SC only
      requires a conventional sequencer device and enables automation and high
      throughput. In addition, it proved to be transferable to a different laboratory.
      The number of authorized GMO events is rapidly growing; and the acreage of
      genetically modified (GM) varieties cultivated and commercialized worldwide is
      rapidly increasing. In this context, our multiplex PCR-CGE-SC can be suitable for
      screening GM contents in food.

PMID- 16972303
TI  - Parallel optimization and genotyping of multiple single-nucleotide polymorphism
      markers by sample pooling approach using cycling-gradient CE with multiple
      injections.
AB  - Increasing importance of single-nucleotide polymorphisms (SNPs) in determination
      of disease susceptibility or in prediction of therapy response brings attention
      of many molecular diagnostic laboratories to simple and low-cost SNP genotyping
      methodologies. We have recently introduced a mutation detection technique based
      on analysis of homo- and heteroduplex PCR fragments resolved in cycling
      temperature gradient conditions on a conventional multicapillary-array DNA
      sequencer. The main advantage of this technique is in its simplicity with no
      requirement for sample cleanup prior to the analysis. In this report we present a
      practical application of the technology for genotyping of SNP markers in two
      separate clinical projects resulting in a combined set of 44 markers screened in
      over 500 patients. Initially, a design of PCR primers and conditions was
      performed for each SNP marker. Then, optimization of CE running conditions
      (limited just to the proper selection of temperature cycling) was performed on
      pools of 20 DNA samples to increase the probability of having each of the two
      allele types represented in the sample. After selecting the optimum conditions,
      screening of markers in patients was performed using a multiple-injection
      approach for further acceleration of the sample throughput. The rate of
      successful optimization of experimental conditions without any pre-selection
      based on the SNP sequence or melting characteristics was 80% from the initial SNP
      marker candidates. By studying the failed markers, we attempt to identify
      critical factors enabling successful typing. The presented technique is very
      useful for low to medium sized SNP genotyping projects mostly applied in
      pharmacogenomic research as well as in clinical diagnostics. The main advantages
      include low cost, simple setup and validation of SNP markers.

PMID- 16972304
TI  - An optimized microchip electrophoresis system for mutation detection by tandem
      SSCP and heteroduplex analysis for p53 gene exons 5-9.
AB  - With the complete sequencing of the human genome, there is a growing need for
      rapid, highly sensitive genetic mutation detection methods suitable for clinical
      implementation. DNA-based diagnostics such as single-strand conformational
      polymorphism (SSCP) and heteroduplex analysis (HA) are commonly used in research
      laboratories to screen for mutations, but the slab gel electrophoresis (SGE)
      format is ill-suited for routine clinical use. The translation of these assays
      from SGE to microfluidic chips offers significant speed, cost, and sensitivity
      advantages; however, numerous parameters must be optimized to provide highly
      sensitive mutation detection. Here we present a methodical study of system
      parameters including polymer matrix, wall coating, analysis temperature, and
      electric field strengths on the effectiveness of mutation detection by tandem
      SSCP/HA for DNA samples from exons 5-9 of the p53 gene. The effects of polymer
      matrix concentration and average molar mass were studied for linear
      polyacrylamide (LPA) solutions. We determined that a matrix of 8% w/v 600 kDa LPA
      provides the most reliable SSCP/HA mutation detection on chips. The inclusion of
      a small amount of the dynamic wall-coating polymer poly-N-hydroxyethylacrylamide
      in the matrix substantially improves the resolution of SSCP conformers and
      extends the coating lifetime. We investigated electrophoresis temperatures
      between 17 and 35 degrees C and found that the lowest temperature accessible on
      our chip electrophoresis system gives the best condition for high sensitivity of
      the tandem SSCP/HA method, especially for the SSCP conformers. Finally, the use
      of electrical fields between 350 and 450 V/cm provided rapid separations (<10
      min) with well-resolved DNA peaks for both SSCP and HA.

PMID- 16972305
TI  - Gene profiling of cathepsin K deficiency in atherogenesis: profibrotic but
      lipogenic.
AB  - Recently, we showed that cathepsin K deficiency reduces atherosclerotic plaque
      progression, induces plaque fibrosis, but aggravates macrophage foam cell
      formation in the ApoE -/- mouse. To obtain more insight into the molecular
      mechanisms by which cathepsin K disruption evokes the observed phenotypic
      changes, we used microarray analysis for gene expression profiling of aortic
      arches of CatK -/-/ApoE -/- and ApoE -/- mice on a mouse oligo microarray. Out of
      20 280 reporters, 444 were significantly differentially expressed (p-value of <
      0.05, fold change of > or = 1.4 or < or = - 1.4, and intensity value of > 2.5
      times background in at least one channel). Ingenuity Pathway Analysis and GenMAPP
      revealed upregulation of genes involved in lipid uptake, trafficking, and
      intracellular storage, including caveolin - 1, - 2, - 3 and CD36, and profibrotic
      genes involved in transforming growth factor beta (TGFbeta) signalling, including
      TGFbeta2, latent TGFbeta binding protein-1 (LTBP1), and secreted protein, acidic
      and rich in cysteine (SPARC), in CatK -/-/ApoE -/- mice. Differential gene
      expression was confirmed at the mRNA and protein levels. In vitro modified low
      density lipoprotein (LDL) uptake assays, using bone marrow derived macrophages
      preincubated with caveolae and scavenger receptor inhibitors, confirmed the
      importance of caveolins and CD36 in increasing modified LDL uptake in the absence
      of cathepsin K. In conclusion, we suggest that cathepsin K deficiency alters
      plaque phenotype not only by decreasing proteolytic activity, but also by
      stimulating TGFbeta signalling. Besides this profibrotic effect, cathepsin K
      deficiency has a lipogenic effect owing to increased lipid uptake mediated by
      CD36 and caveolins.

PMID- 16972306
TI  - NMR assessment of the global shape of a non-labelled DNA dodecamer containing a
      tandem of G-T mismatches.
AB  - We have carried out a solution study of two non-labelled self-complementary DNA
      dodecamers d(GACTGTACAGTC)2 and d(GACTGTGCAGTC)2 by NMR, the second sequence
      composed of two G-T mismatches. Structures were determined using distances
      extracted from NOE effects alone or using both NOE and RDC constraints, measured
      in three different liquid crystalline media. We ensured that our data on the
      influence of the mesogen on the DNA structures, and the way in which the RDCs
      were incorporated as constraints in the protocol refinement, were consistent. We
      also tested the influence of different sets of RDCs and the best means of
      optimizing the calculation of D(a) and R. Resolution and accuracy of the ten best
      energy final structures were compared. The addition of a small set of RDC
      constraints significantly improves the final determined structures. We took
      advantage of the specificity of the RDC, i.e. it contains orientational
      information, and explored the global shape of the DNA duplexes; it was found that
      the duplexes do not have a large curvature. For the G-T base pair, we observed,
      in this particular sequence (tandem of G-T mismatches), a new pattern of base
      pairing, which involved the formation of a bifurcated hydrogen bond.

PMID- 16972307
TI  - Expression, purification, and physicochemical characterization of the N-terminal
      active site of human angiotensin-I converting enzyme.
AB  - We have cloned, over expressed, and purified one of the two catalytic domains
      (residues Ala361 to Gly468, ACE-N) of human somatic angiotensin-I converting
      enzyme in Escherichia coli. This construct represents the N-catalytic domain
      including the two binding motifs and the 23 amino acid spacers as well as some
      amino acid residues before and after the motifs that might help in correct
      conformation. The overexpressed protein was exclusively localized to insoluble
      inclusion bodies. Inclusion bodies were solubilized in an 8-M urea buffer.
      Purification was carried out by differential centrifugation and gel filtration
      chromatography under denaturing conditions. About 12 mg of ACE-N peptide per
      liter of bacterial culture was obtained. The integrity of recombinant protein
      domain was confirmed by ESI/MS. Structural analysis using CD spectroscopy has
      shown that, in the presence of TFE, the ACE-N protein fragment has taken a
      conformation, which is consistent with the one found in testis ACE by X-ray
      crystallography. This purification procedure enables the production of an
      isotopically labeled protein fragment for structural studying in solution by NMR
      spectroscopy.

PMID- 16972308
TI  - Density functional computations of 99Ru chemical shifts: relativistic effects,
      influence of the density functional, and study of solvent effects on fac
      [Ru(CO)3I3]-.
AB  - Solvent effects on the 99Ru NMR chemical shift of the complex fac-[Ru(CO)3I3]-
      are investigated computationally using density functional theory. Further,
      benchmark calculations of the 99Ru shift for a set of ten Ru complexes have been
      performed in order to calibrate the computational model and to determine the
      importance of relativistic effects on the 99Ru nuclear magnetic shielding and on
      the chemical shift. A computational model for fac-[Ru(CO)3I3]- that includes both
      explicit solvent molecules and a continuum model is shown to yield the best
      agreement with experiment. Relativistic corrections are shown to be of minor
      importance for determining 99Ru chemical shifts. On the other hand, the nature of
      the density functional is of importance. In agreement with literature data for
      ligand trends of 99Ru chemical shifts, the chemical shift range for different
      solvents is also best reproduced by a hybrid functional.

PMID- 16972309
TI  - Time-sharing evolution and sensitivity enhancements in 2D HSQC-TOCSY and HSQMBC
      experiments.
AB  - Modifications of time-shared (TS) HSQC-like experiments originally developed by
      Griesinger and co-workers (Sattler M, Maurer M, Schleucher J, Griesinger C. J.
      Biomol. NMR 1995; 5: 97) are proposed to extract different types of information
      from a single NMR pulse scheme. It is shown that simultaneous acquisition of
      1H,13C and 1H,15N HSQC-TOCSY and HSQMBC experiments can afford experimental
      sensitivity enhancements of 20-40% with respect to the separate acquisition of
      individual 13C or 15N data. In addition, the incorporation of a number of
      independent editing elements can be easily used for different purposes, for
      instance, to assign unambiguously 1H, 13C, and 15N chemical shifts, to
      differentiate directly from relayed cross-peaks, or to measure simultaneously
      long-range proton-carbon and proton-nitrogen coupling constants. The suggested
      methodologies can be applied to many different classes of nitrogen-containing
      compounds and illustrative examples are provided for the peptide cyclosporine as
      a demonstration of the performance of such experiments.

PMID- 16972310
TI  - Direct NMR resonance assignments of the active site histidine residue in
      Escherichia coli thioesterase I/protease I/lysophospholipase L1.
AB  - Owing to the hydrogen-bond interaction and rapid exchange rate with the bulk
      water, the transverse relaxation time for the N(delta1)-H proton of the catalytic
      histidine in Escherichia coli thioesterase I/protease I/lysophospholipase L1 (TEP
      I) is rather short. Because of its catalytic importance, it is desirable to
      detect and assign this proton resonance. In this paper, we report the first
      direct NMR correlation between the short-lived N(delta1)-H proton and its
      covalently attached N(delta1)-nitrogen of the catalytic His157 residue in E. coli
      thioesterase/protease I. We have used gradient-enhanced jump-return spin-echo
      HMQC (GE-JR SE HMQC) to obtain a direct correlation between the short-lived
      N(delta1)-H proton and its covalently attached N(delta1)-nitrogen. The
      sensitivity of detection for the short-lived N(delta1)-H proton was enhanced
      substantially by improved water suppression, in particular, the suppression of
      radiation damping via pulsed field gradients.

PMID- 16972311
TI  - Malabsorption syndrome with and without small intestinal bacterial overgrowth: a
      study on upper-gut aspirate using 1H NMR spectroscopy.
AB  - Biochemicals in the upper-gut aspirate in 31 patients with malabsorption syndrome
      (MAS) with and without small intestinal bacterial overgrowth (SIBO), and 10
      disease-free controls were analyzed using high-resolution (1)H-NMR spectroscopy,
      and were correlated with the degree of SIBO and severity of MAS. Compared to
      controls, the patients had higher quantities (micromol/L: median [range]) of
      total bile acids/cholesterol (2000 [0-12000] vs. 300 [0-600]), lactate (700 [0
      5200] vs. nil [0-30]), acetate (200 [0-6500] vs. 20 [0-200]), and formate (80 [0
      900] vs. nil [0-50]) (P < 0.01, Mann-Whitney U-test). However, amino acids and
      glucose were comparable in both. Quantities (micromol/L: median [range]) of
      acetate (1330 [220-6500] vs. 100 [0-1430]), lactate (1430 [670-3300] vs. 300 [0
      5200]), formate (360 [0-600] vs. 25 [0-800]), and unconjugated bile acids (500
      [40-600] vs. 10 [0-300]) were higher in MAS patients with SIBO than those without
      SIBO (P < 0.01, Mann-Whitney U-test, for all). In patients with MAS the quantity
      of acetate positively correlated with the degree of SIBO, and unconjugated bile
      acids correlated with the degree of steatorrhoea (Spearman's rank correlation
      coefficient, two-tailed, P < 0.05: 0.46 and 0.52, respectively). This study
      demonstrates the bacterial production of metabolites and deconjugation of bile
      acids in patients with MAS.

PMID- 16972312
TI  - Self-organization of spiking neural network that generates autonomous behavior in
      a real mobile robot.
AB  - In this paper, we propose self-organization algorithm of spiking neural network
      (SNN) applicable to autonomous robot for generation of adoptive and goal-directed
      behavior. First, we formulated a SNN model whose inputs and outputs were analog
      and the hidden unites are interconnected each other. Next, we implemented it into
      a miniature mobile robot Khepera. In order to see whether or not a solution(s)
      for the given task(s) exists with the SNN, the robot was evolved with the genetic
      algorithm in the environment. The robot acquired the obstacle avoidance and
      navigation task successfully, exhibiting the presence of the solution. After
      that, a self-organization algorithm based on a use-dependent synaptic
      potentiation and depotentiation at synapses of input layer to hidden layer and of
      hidden layer to output layer was formulated and implemented into the robot. In
      the environment, the robot incrementally organized the network and the given
      tasks were successfully performed. The time needed to acquire the desired
      adoptive and goal-directed behavior using the proposed self-organization method
      was much less than that with the genetic evolution, approximately one fifth.

PMID- 16972313
TI  - A neural network model for the simulation of word production errors of Finnish
      nouns.
AB  - We constructed a connectionist model with multilayer perceptron networks for the
      simulation of word production errors in the Finnish language. Such errors occur
      as slips of the tongue in healthy subjects and even more often in aphasic
      patients suffering from brain damage. Word production errors are of theoretical
      interest as they open an avenue to inner workings of the language production
      system. Here we present our coding schemes for semantic and phoneme information
      of words, investigate the general properties of the model, and compare the
      results of the model against empirical naming error data from ten aphasic
      patients. The model was reasonable in simulating word production errors in this
      heterogeneous group of aphasic patients.

PMID- 16972314
TI  - Pose estimation in automated visual inspection using genetic algorithm.
AB  - In this paper, we propose a genetic algorithm based approach to determine the
      pose of an object in Automated Visual Inspection having three degrees of freedom.
      We have investigated the effect of noise at 20 dB SNR and also mismatch resulting
      from incorrect correspondences between the object space points and the image
      space points, on the estimation of pose parameters. The maximum error in
      translation parameters is less than 0.45 cm and rotational error is less than 0.2
      degree at 20 dB SNR. The error in parameter estimation is insignificant upto 7
      pairs of mismatched points out of 24 points in object space and the results
      skyrockets when 8 or more pairs of points are mismatched. We have compared our
      result with that obtained by least square technique and it shows that GA based
      method outperform the gradient based technique when the number of vertices of the
      object to be inspected is small. These results have clearly established the
      robustness of GA in estimating the pose of an object with small number of
      vertices in automated visual inspection.

PMID- 16972315
TI  - ON the influence of parameter theta- on performance of RBF neural networks
      trained with the dynamic decay adjustment algorithm.
AB  - The dynamic decay adjustment (DDA) algorithm is a fast constructive algorithm for
      training RBF neural networks (RBFNs) and probabilistic neural networks (PNNs).
      The algorithm has two parameters, namely, theta(+) and theta(-). The papers which
      introduced DDA argued that those parameters would not heavily influence
      classification performance and therefore they recommended using always the
      default values of these parameters. In contrast, this paper shows that smaller
      values of parameter theta(-) can, for a considerable number of datasets, result
      in strong improvement in generalization performance. The experiments described
      here were carried out using twenty benchmark classification datasets from both
      Proben1 and the UCI repositories. The results show that for eleven of the
      datasets, the parameter theta(-) strongly influenced classification performance.
      The influence of theta(-) was also noticeable, although much less, on six of the
      datasets considered. This paper also compares the performance of RBF-DDA with
      theta(-) selection with both AdaBoost and Support Vector Machines (SVMs).

PMID- 16972316
TI  - Pruning and model-selecting algorithms in the RBF frameworks constructed by
      support vector learning.
AB  - This paper presents the pruning and model-selecting algorithms to the support
      vector learning for sample classification and function regression. When
      constructing RBF network by support vector learning we occasionally obtain
      redundant support vectors which do not significantly affect the final
      classification and function approximation results. The pruning algorithms
      primarily based on the sensitivity measure and the penalty term. The kernel
      function parameters and the position of each support vector are updated in order
      to have minimal increase in error, and this makes the structure of SVM network
      more flexible. We illustrate this approach with synthetic data simulation and
      face detection problem in order to demonstrate the pruning effectiveness.

PMID- 16972317
TI  - A delayed neural network method for solving convex optimization problems.
AB  - In this paper, the delayed projection neural network for a class of solving
      convex programming problem is proposed. The existence of solution and global
      exponential stability of the proposed network are proved, which can guarantee to
      converge at an exact optimal solution of the convex programming problems. Several
      examples are given to show the effectiveness of the proposed network.

PMID- 16972318
TI  - Dynamic output feedback stabilization for nonlinear systems based on standard
      neural network models.
AB  - A neural-model-based control design for some nonlinear systems is addressed. The
      design approach is to approximate the nonlinear systems with neural networks of
      which the activation functions satisfy the sector conditions. A novel neural
      network model termed standard neural network model (SNNM) is advanced for
      describing this class of approximating neural networks. Full-order dynamic output
      feedback control laws are then designed for the SNNMs with inputs and outputs to
      stabilize the closed-loop systems. The control design equations are shown to be a
      set of linear matrix inequalities (LMIs) which can be easily solved by various
      convex optimization algorithms to determine the control signals. It is shown that
      most neural-network-based nonlinear systems can be transformed into input-output
      SNNMs to be stabilization synthesized in a unified way. Finally, some application
      examples are presented to illustrate the control design procedures.

PMID- 16972319
TI  - Aluminium tolerance in barley (Hordeum vulgare L.): physiological mechanisms,
      genetics and screening methods.
AB  - Aluminium (Al) toxicity is one of the major limiting factors for barley
      production on acid soils. It inhibits root cell division and elongation, thus
      reducing water and nutrient uptake, consequently resulting in poor plant growth
      and yield. Plants tolerate Al either through external resistance mechanisms, by
      which Al is excluded from plant tissues or internal tolerance mechanisms,
      conferring the ability of plants to tolerate Al ion in the plant symplasm where
      Al that has permeated the plasmalemma is sequestered or converted into an
      innocuous form. Barley is considered to be most sensitive to Al toxicity among
      cereal species. Al tolerance in barley has been assessed by several methods, such
      as nutrient solution culture, soil bioassay and field screening. Genetic and
      molecular mapping research has shown that Al tolerance in barley is controlled by
      a single locus which is located on chromosome 4H. Molecular markers linked with
      Al tolerance loci have been identified and validated in a range of diverse
      populations. This paper reviews the (1) screening methods for evaluating Al
      tolerance, (2) genetics and (3) mechanisms underlying Al tolerance in barley.

PMID- 16972320
TI  - A kinetic approach to evaluate salinity effects on carbon mineralization in a
      plant residue-amended soil.
AB  - The interaction of salinity stress and plant residue quality on C mineralization
      kinetics in soil is not well understood. A laboratory experiment was conducted to
      study the effects of salinity stress on C mineralization kinetics in a soil
      amended with alfalfa, wheat and corn residues. A factorial combination of two
      salinity levels (0.97 and 18.2 dS/m) and four levels of plant residues (control,
      alfalfa, wheat and corn) with three replications was performed. A first order
      kinetic model was used to describe the C mineralization and to calculate the
      potentially mineralizable C. The CO(2)-C evolved under non-saline condition,
      ranged from 814.6 to 4842.4 mg CO(2)-C/kg in control and alfalfa residue-amended
      soils, respectively. Salinization reduced the rates of CO(2) evolution by 18.7%,
      6.2% and 5.2% in alfalfa, wheat and corn residue-amended soils, respectively.
      Potentially mineralizable C (C(0)) was reduced significantly in salinized alfalfa
      residue-treated soils whereas, no significant difference was observed for control
      treatments as well as wheat and corn residue-treated soils. We concluded that the
      response pattern of C mineralization to salinity stress depended on the plant
      residue quality and duration of incubation.

PMID- 16972321
TI  - Application Fourier transform near infrared spectrometer in rapid estimation of
      soluble solids content of intact citrus fruits.
AB  - Nondestructive method of measuring soluble solids content (SSC) of citrus fruits
      was developed using Fourier transform near infrared reflectance (FT-NIR)
      measurements collected through optics fiber. The models describing the
      relationship between SSC and the NIR spectra of citrus fruits were developed and
      evaluated. Different spectra correction algorithms (standard normal variate
      (SNV), multiplicative signal correction (MSC)) were used in this study. The
      relationship between laboratory SSC and FT-NIR spectra of citrus fruits was
      analyzed via principle component regression (PCR) and partial least squares (PLS)
      regression method. Models based on the different spectral ranges were compared in
      this research. The first derivative and second derivative were applied to all
      spectra to reduce the effects of sample size, light scattering, instrument noise,
      etc. Different baseline correction methods were applied to improve the spectral
      data quality. Among them the second derivative method after baseline correction
      produced best noise removing capability and yielded optimal calibration models. A
      total of 170 NIR spectra were acquired; 135 NIR spectra were used to develop the
      calibration model; the remaining spectra were used to validate the model. The
      developed PLS model describing the relationship between SSC and NIR reflectance
      spectra could predict SSC of 35 samples with correlation coefficient of 0.995 and
      RMSEP of 0.79 degrees Brix.

PMID- 16972322
TI  - Synthesis and paste properties of octenyl succinic anhydride modified early
      Indica rice starch.
AB  - Octenyl succinic anhydride (OSA) modified early Indica rice starch was prepared
      in aqueous slurry systems using response surface methodology. The paste
      properties of the OSA starch were also investigated. Results indicated that the
      suitable parameters for the preparation of OSA starch from early Indica rice
      starch were as follows: reaction period 4 h, reaction temperature 33.4 degrees C,
      pH of reaction system 8.4, concentration of starch slurry 36.8% (in proportion to
      water, w/w), amount of OSA 3% (in proportion to starch, w/w). The degree of
      substitution was 0.0188 and the reaction efficiency was 81.0%. The results of
      paste properties showed that with increased OSA modification, the starch
      derivatives had higher paste clarity, decreased retrogradation and better freeze
      thaw stability.

PMID- 16972323
TI  - Computational prediction of microRNA genes in silkworm genome.
AB  - MicroRNAs (miRNAs) constitute a novel, extensive class of small RNAs
      (approximately 21 nucleotides), and play important gene-regulation roles during
      growth and development in various organisms. Here we conducted a homology search
      to identify homologs of previously validated miRNAs from silkworm genome. We
      identified 24 potential miRNA genes, and gave each of them a name according to
      the common criteria. Interestingly, we found that a great number of newly
      identified miRNAs were conserved in silkworm and Drosophila, and family alignment
      revealed that miRNA families might possess single nucleotide polymorphisms. miRNA
      gene clusters and possible functions of complement miRNA pairs are discussed.

PMID- 16972324
TI  - Osteogenic potential of human periosteum-derived progenitor cells in PLGA
      scaffold using allogeneic serum.
AB  - The use of periosteum-derived progenitor cells (PCs) combined with bioresorbable
      materials is an attractive approach for tissue engineering. The aim of this study
      was to characterize the osteogenic differentiation of PC in 3-dimensional (3D)
      poly-lactic-co-glycolic acid (PLGA) fleeces cultured in medium containing
      allogeneic human serum. PCs were isolated and expanded in monolayer culture.
      Expanded cells of passage 3 were seeded into PLGA constructs and cultured in
      osteogenic medium for a maximum period of 28 d. Morphological, histological and
      cell viability analyses of three-dimensionally cultured PCs were performed to
      elucidate osseous synthesis and deposition of a calcified matrix. Furthermore,
      the mRNA expression of type I collagen, osteocalcin and osteonectin was semi
      quantitively evaluated by real-time reverse transcriptase-polymerase chain
      reaction (RT-PCR). The fibrin gel immobilization technique provided homogeneous
      PCs distribution in 3D PLGA constructs. Live-dead staining indicated a high
      viability rate of PCs inside the PLGA scaffolds. Secreted nodules of neo-bone
      tissue formation and the presence of matrix mineralization were confirmed by
      positive von Kossa staining. The osteogenic differentiation of PCs was further
      demonstrated by the detection of type I collagen, osteocalcin and osteonectin
      gene expression. The results of this study support the concept that this tissue
      engineering method presents a promising method for creation of new bone in vivo.

PMID- 16972325
TI  - Inhibitive effects of anti-oxidative vitamins on mannitol-induced apoptosis of
      vascular endothelial cells.
AB  - OBJECTIVE: Study blood vessel injury and gene expression indicating vascular
      endothelial cell apoptosis induced by mannitol with and without administration of
      anti-oxidative vitamins. METHODS: Healthy rabbits were randomly divided into four
      groups. Mannitol was injected into the vein of the rabbit ear in each animal. Pre
      treatment prior to mannitol injection was performed with normal saline (group B),
      vitamin C (group C) and vitamin E (group D). Blood vessel injury was assessed
      under electron and light microscopy. In a second experiment, cell culture
      specimen of human umbilical vein endothelial cells were treated with mannitol.
      Pre-treatment was done with normal saline (sample B), vitamin C (sample C) and
      vitamin E (sample D). Total RNA was extracted with the original single step
      procedure, followed by hybridisation and analysis of gene expression. RESULTS: In
      the animal experiment, serious blood vessel injury was seen in group A and group
      B. Group D showed light injury only, and normal tissue without pathological
      changes was seen in group C. Of all 330 apoptosis-related genes analysed in human
      cell culture specimen, no significant difference was seen after pre-treatment
      with normal saline, compared with the gene chip without pre-treatment. On the
      gene chip pre-treated with vitamin C, 45 apoptosis genes were down-regulated and
      34 anti-apoptosis genes were up-regulated. Pre-treatment with vitamin E resulted
      in the down-regulation of 3 apoptosis genes. CONCLUSION: Vitamin C can protect
      vascular endothelial cells from mannitol-induced injury.

PMID- 16972326
TI  - Inactivation of the tumor suppressor Kruppel-like factor 6 (KLF6) by mutation or
      decreased expression in hepatocellular carcinomas.
AB  - BACKGROUND AND AIM: The Kruppel-like transcription factor KLF6 is a novel tumor
      suppressor gene. It was inactivated in human prostate cancer and other tumors
      tissue, as the result of frequent mutation and loss of heterozygosity (LOH).
      However, there is no data reporting the levels of KLF6 both mRNA and protein in
      hepatocellular carcinomas (HCCs). We therefore detected mutations and expression
      of KLF6 in HCC tissues and further observed the effect of it on cell growth in
      HCC cell lines. METHODS: We analyzed the exon-2 of KLF6 gene by direct DNA
      sequencing, and detected the expression of KLF6 by RT-PCR and Western blot in 23
      HCC tissues and corresponding nontumorous tissues. Loss of growth suppressive
      effect of the HCC-derived KLF6 mutant was characterized by in vitro growth curves
      plotted, flow cytometry and Western blotting. RESULTS: KLF6 mutations were found
      in 2 of 23 HCC tissues and one of mutations was missense. Expression of KLF6 mRNA
      or protein was down-regulated in 8 (34.7%) or 9 (39.1%) of 23 HCC tissues. Wild
      type KLF6 (wtKLF6) inhibited cellular proliferation and prolonged G1-S transition
      by inducing the expression of p21WAF1 following stable transfection into cultured
      HepG2 cells, but tumor-derived KLF6 mutant (mKLF6) had no effects. CONCLUSION:
      Our findings suggest that KLF6 may be involved in pathogenesis of HCC.

PMID- 16972327
TI  - Inhibition of expression of vascular endothelial growth factor and its receptors
      in pulmonary adenocarcinoma cell by TNP-470 in combination with gemcitabine.
AB  - Angiogenesis is required for solid tumor growth and facilitates tumor progression
      and metastasis. The inhibition effects of O-(chloroacetyl-carbamoyl) fumagillol
      (TNP-470), an angiogenesis inhibitor, and gemcitabine, a chemotherapeutic agent,
      on expression of growth factors were investigated using human pulmonary
      adenocarcinoma cell line, A549. The A549 cells were divided into four groups:
      control group, 10(-6) mg/ml gemcitabine treated group, 10(-4) mg/ml TNP-470
      treated group and gemcitabine+TNP-470 treated group. The mRNA and protein
      expression of vascular endothelial growth factor (VEGF) and its receptors, FMS
      like tyrosine kinase-1 (FLT-1) and kinase insert domain-containing receptor
      (KDR), in different groups were measured. The growth of A549 cell cultured with
      gemcitabine or TNP-470 was inhibited in an almost dose-dependent manner. Although
      gemcitabine (10(-6) mg/ml) alone and TNP-470 (10(-4) mg/ml) alone had no effect
      on the mRNA and protein expression of VEGF and its receptors (FLT-1, KDR) in A549
      cells compared to the control (P>0.05), 10(-6) mg/ml gemcitabine in combination
      with 10(-4) mg/ml TNP-470 had significant effect (P<0.01). Moreover, combination
      of the two drugs significantly inhibited the mRNA expression of VEGF, FLT-1 and
      KDR compared to either drug alone (P<0.05). This study suggests that combined
      treatment with TNP-470 plus gemcitabine may augment the antiangiogenic and
      antineoplastic effects in lung cancer cells in vitro.

PMID- 16972328
TI  - Characterization of surface EMG signals using improved approximate entropy.
AB  - An improved approximate entropy (ApEn) is presented and applied to characterize
      surface electromyography (sEMG) signals. In most previous experiments using
      nonlinear dynamic analysis, this certain processing was often confronted with the
      problem of insufficient data points and noisy circumstances, which led to
      unsatisfactory results. Compared with fractal dimension as well as the standard
      ApEn, the improved ApEn can extract information underlying sEMG signals more
      efficiently and accurately. The method introduced here can also be applied to
      other medium-sized and noisy physiological signals.

PMID- 16972329
TI  - HIV/AIDS care in the border region: demystifying the misconceptions.

PMID- 16972330
TI  - HIV and race. Black mobilization plans to control spread of HIV in five years.

PMID- 16972332
TI  - Medical marijuana case to be retried over juror misconduct.

PMID- 16972333
TI  - HIV and politics. AIDSVote offers campaign materials to election activists.

PMID- 16972331
TI  - Education. Students become HIV ambassadors to teens.

PMID- 16972334
TI  - Exposure. HIV-positive man's conviction for spitting on officer upheld.

PMID- 16972336
TI  - County officials denied dismissal over HIV discrimination.

PMID- 16972335
TI  - Conviction reversed over lack of drug interaction testimony.

PMID- 16972337
TI  - [Abecedary of the "Annales". Part 5].
AB  - The terms included and detailed in the present part are: Consort statement, Odds
      ratio, Receiver Operating Characteristics curve.

PMID- 16972338
TI  - [Abecedary of the "Annales". Part 1].
AB  - The terms included and detailed in the present part are: protocol, alpha risk,
      (standardised) effect size, intention to treat analysis, linear multiple and
      logistic regressions, and sensitivity analysis.

PMID- 16972339
TI  - [Abecedary of the "Annales". Part 4].
AB  - The terms included and detailed in the present part are: case-control Study, Chi
      scare, Cochrane Collaboration, Cochrane Library, Cohort study, Coefficient of
      correlation, concordance testing, Informed consent.

PMID- 16972340
TI  - Erratum to "Sparing of the submandibular glands by intensity modulated
      radiotherapy in the treatment of head and neck cancer" [Radiother. Oncol. 78
      (2006) 270-275].

PMID- 16972341
TI  - When doctors hide medical errors.

PMID- 16972342
TI  - Ureteral and renal endoscopy. A new approach. 1982.

PMID- 16972343
TI  - Extracorporeal shock-wave lithotripsy: one-year experience with the Dornier
      lithotripter. 1985.

PMID- 16972344
TI  - Managing glaucoma during pregnancy.

PMID- 16972345
TI  - Rabies remains a 'neglected disease'.

PMID- 16972346
TI  - [Optimized implantation of a titanium shell for a partially implanted air
      conduction hearing aid system].

PMID- 16972347
TI  - Non-suppression of testosterone in patients with a rising prostate-specific
      antigen level receiving luteinising hormone-releasing hormone analogues for
      metastatic prostate cancer.

PMID- 16972348
TI  - The Frank Ellis Lecture by Eric Hall.

PMID- 16972349
TI  - Self-exclusion behaviours of people with gastrointestinal illness who work in
      high-risk settings or attend daycare.

PMID- 16972350
TI  - Streptococcus pneumoniae outbreak in a rural Regina community.

PMID- 16972351
TI  - Clostridium difficile: more and meaner.

PMID- 16972352
TI  - Salmonella typhimurium DT1204, Italy.

PMID- 16972353
TI  - Nonsteroidal antiinflammatory drugs and group A streptococcal infection.

PMID- 16972354
TI  - Detecting Clostridium botulinum.

PMID- 16972355
TI  - New World hantavirus in humans, French Guiana.

PMID- 16972356
TI  - Qinghai-like H5N1 from domestic cats, northern Iraq.

PMID- 16972357
TI  - Classifying Escherichia coli.

PMID- 16972358
TI  - Toscana virus RNA in Sergentomyia minuta files.

PMID- 16972359
TI  - Rat-bite fever, Canada.

PMID- 16972360
TI  - Cutaneous injury and Vibrio vulnificus infection.

PMID- 16972361
TI  - Neorickettsia helminthoeca in dog, Brazil.

PMID- 16972362
TI  - Art, science, and life's enigmas.

PMID- 16972363
TI  - Proceedings of the 27th Symposium on Biotechnology for Fuels and Chemicals, May 1
      4, 2005, Denver, Colorado, USA.

PMID- 16972364
TI  - [Proceedings of National Gastroenterology Week, Acapulco, Mexico, November 2004].

PMID- 16972365
TI  - AJO history of ophthalmology series. Thomas Young (1773-1829).

PMID- 16972366
TI  - [Image of the week. Multiple coronary fistulae with left ventricle drainage].

PMID- 16972367
TI  - The William Nelson ECG quiz.

PMID- 16972368
TI  - Continuing bonds in adaptation to bereavement: introduction.
AB  - The role of the continuing bond to the deceased in adjustment to bereavement has
      been given considerable attention in the bereavement literature. It is
      increasingly recognized that it is a normative part of adjustment to the loss of
      a loved one and that it can be adaptive. It may be the case however that a
      continuing bond to the deceased may also be maladaptive under certain conditions.
      In this special topic series of articles, the implications of a continuing bond
      for adjustment to bereavement is addressed. Conceptually and empirically focused
      papers as well as clinically oriented papers on the continuing bond to the
      deceased have been included in order to provide the reader with a broad sampling
      of contemporary work in this area. The aim is to inspire further thinking and
      research on this topic as well as to promote greater awareness among grief
      counselors and practitioners on the importance of the continuing bond to the
      deceased in working with the bereaved.

PMID- 16972369
TI  - Continuing bonds and reconstructing meaning: mitigating complications in
      bereavement.
AB  - Drawing on attachment theory and constructivist conceptualizations of
      bereavement, the authors assessed the relation between continuing bonds coping
      and meaning reconstruction following the death of a loved one and complicated
      grief symptomatology. Five hundred six young adults in the first two years of
      bereavement from a variety of losses completed the Inventory of Complicated Grief
      along with measures of the strength of their ongoing attachment to the deceased
      and their capacity to make sense of the loss, find benefit in the experience, and
      reconstruct a progressive sense of identity following the death. Several
      variables concerning the survivor, his or her relationship to the deceased, and
      the nature of the death functioned as risk factors for heightened distress, but
      their role was generally moderated by meaning-making, often to the point of non
      significance. In contrast, higher levels of benefit-finding and positive identity
      change were associated with lower levels of bereavement complication. Finally, an
      interaction emerged between sense-making and ongoing attachment to the deceased,
      suggesting that strong continuing bonds predicted greater levels of traumatic and
      especially separation distress, but only when the survivor was unable to make
      sense of the loss in personal, practical, existential, or spiritual terms.

PMID- 16972370
TI  - Unresolved grief and continuing bonds: an attachment perspective.
AB  - Much of the contemporary bereavement literature on the continuing bond to the
      deceased (CB) has emphasized its adaptiveness and given limited attention to when
      it may be maladaptive. The attachment literature on disorganized-unresolved
      attachment classification in relation to loss, or "unresolved loss," is
      informative in identifying CB expressions that are indicative of failure to
      integrate the death of a loved one. In this article, an important linkage is
      identified between a prominent indicator of unresolved loss that involves a lapse
      in the monitoring of reasoning implying disbelief that the person is dead and the
      clinical writings of J. Bowlby (1980) and V. D. Volkan (1981) on maladaptive
      variants of CB expression. The aim is to highlight the value of the attachment
      literature on unresolved loss in clarifying the conditions under which CB is
      likely to be maladaptive.

PMID- 16972371
TI  - Mahr calls for 'one health' initiative.

PMID- 16972372
TI  - Comments on the future of food supply veterinary medicine.

PMID- 16972373
TI  - Continuing relationships with the deceased: disentangling bonds and grief.
AB  - Some studies of the relationship between continuing bonds and grief intensity
      have claimed that continuing bonds lead to poor adaptation to bereavement.
      However, operationalizations of continuing bonds and grief intensity appear to
      overlap conceptually. Thus, it is still unclear what character the connection
      between continuing bonds and grief bears and how strong the relationship is.
      Three studies are reported, 2 of which examine the perception of conceptual
      overlap between continuing bonds and grief intensity, and 1 that examines whether
      reducing this perceived conceptual overlap affects the association between
      continuing bonds and grief intensity. In the first 2 studies, extent of
      perception of conceptual overlap was established, and subscales for the bonds and
      grief measures were derived that could be considered less overlapping. In the
      third study, relationships between bonds, grief, and well-being were calculated
      for the original scales and those reduced on the basis of deleted perceived
      overlap. When conceptual overlap was reduced, the relationship between grief and
      continuing bonds was slightly lower but not significantly so, as happened to the
      relationship between bonds and well-being. By contrast, the link between grief
      intensity and well-being did not diminish after deleting the overlapping items.
      These patterns suggest that future research should continue to explore whether
      the association between continuing bonds and grief intensity is due to conceptual
      overlap.

PMID- 16972374
TI  - Continuing bonds and grief: a prospective analysis.
AB  - Using data of 56 bereaved individuals, this study examined associations of
      various manifestations of continuing bonds, assessed at 7-12 months post-loss,
      with concurrent and prospective (9 months later) symptoms of grief and
      depression. Among other things it was found that, independent of initial symptom
      levels, manifestations of continuing bonds differed in their associations with
      subsequent grief and depression. That is, continuing bonds through recovering
      memories was a strong predictor of grief but not depression, whereas continuing
      bonds through the use of the deceased's possessions was a weak predictor of both
      grief and depression. In part, these findings contradict earlier prospective
      findings.

PMID- 16972375
TI  - Stanford to ban drug makers' gifts to doctors, even pens.

PMID- 16972376
TI  - The wide, wild world of genetic testing.

PMID- 16972377
TI  - Counseling older adults with dementia who are dealing with death: innovative
      interventions for practitioners.
AB  - As individuals age, they deal with an increasing number of emotional, physical,
      and environmental losses. One loss older adults encounter is their own and
      others' deaths. Older adults with dementia may face greater difficulty in
      understanding and dealing with death-related issues because of cognitive and
      memory changes. Little literature exists to guide the practice of grief
      counseling with this population. Thus, two innovative approaches-spaced retrieval
      and group buddies-will be presented as ways to help individuals with dementia
      deal with issues around death. Two case studies are presented to demonstrate the
      preliminary usefulness of these techniques with clients.

PMID- 16972378
TI  - Destruction of environmental organic pollutants by supercritical water oxidation.
AB  - The supercritical water oxidation of two environmental pollutants in the form of
      diesel fuel and two waste landfill leachate samples have been examined in
      relation to sub-critical and supercritical water oxidation conditions.
      Supercritical water oxidation involves reactions in an aqueous fluid phase under
      conditions below and around the critical point of water (T(c) = 374 degrees C,
      P(c) = 22.1 MPa). Experiments were carried out using a batch autoclave reactor at
      temperatures between 300 degrees C and 380 degrees C corresponding to pressures
      between 10.5 MPa and 22.8 MPa. The oxidative decomposition of the diesel fuel,
      which was loaded onto a sand matrix to simulate a contaminated land sample, was
      determined in relation to process conditions. The results showed that almost
      complete destruction of the components of the diesel fuel could be achieved. In
      addition, intermediate oxygenated compounds were formed and identified. The level
      of loading of the diesel fuel onto the sand matrix influenced the level of
      compound decomposition and the amount of intermediate oxygenated compounds
      formed. The characteristics of the waste landfill leachates were determined and
      were shown to be highly chemically complex. The high chloride concentration of
      the leachate resulted in significant corrosion of the reactor. However, almost
      complete oxidation of the organic components of the leachate could be achieved
      under supercritical water oxidation conditions.

PMID- 16972379
TI  - Effect of synthetic surfactants on the solubilization and distribution of PAHs in
      water/soil-water systems.
AB  - The present study examined the effects of four surfactants, including three non
      ionic surfactants (Tween 80, Triton X-100 and Brij 35) and an anionic surfactant
      SDS on the solubilization and distribution of phenanthrene (Phe) and pyrene (Pyr)
      in soil-water systems. All four surfactants could enhance the solubilization of
      Phe and Pyr in aqueous phase linearly when surfactant concentrations exceeded
      their respective critical micelle concentrations (CMC). Molar solubilization
      ratio (MSR) which indicated surfactant's solubilization capacity for Phe and Pyr,
      was highest for Tween 80 for both PAHs, and SDS had the lowest among the four
      surfactants, while Triton X-100 and Brij 35 had about the same MSR for both PAHs.
      Moreover, all the surfactants could provide a strong micelle partitioning phase
      for the more hydrophobic Pyr than Phe as revealed by their high micelle--aqueous
      phase partition coefficient, K(mc). Batch desorption studies also demonstrated
      that Tween 80 had the best capacity for the desorption of both Phe and Pyr in the
      soil-water systems, and followed by Triton X-100 and Brij 35, while SDS seems to
      have no positive effect on the desorption of PAHs probably due to its relatively
      high CMC value. Therefore, from the application standpoint, the results obtained
      in this study suggest that Tween 80 would be the most suitable candidate among
      the four surfactants in improving solubilization and desorption of PAHs in soil
      water system, which are believed to be the prerequisites for successful
      bioremediation technology for PAH contaminated soil.

PMID- 16972380
TI  - Treatment of toxic industrial wastewater in fluidized and fixed-bed batch
      reactors with Trametes versicolor: influence of immobilisation.
AB  - This work presents the results obtained in the treatment of industrial pulp mill
      wastewater (black liquor) with the white-rot fungus Trametes versicolor
      immobilised in nylon and polyurethane foam cubes. Reductions in colour (36%),
      aromatic compounds (54%) and toxicity (3.15 times reduction of the initial value)
      were obtained when the fungus was immobilised in nylon and good toxicity
      reduction (5.7-fold reduction of the initial value) when polyurethane foam was
      used. These results were compared with those obtained with Trametes versicolor in
      the form of pellets for colour and aromatic compounds (84.8% and 70.2%
      respectively). Correlations among different parameters have been studied.
      Relationships between colour and changes in the molecular weight distribution
      profiles, as well as a correlation between laccase production and toxicity
      reduction have been found. For laccase production vs. toxicity reduction a
      different behaviour has been observed depending on the bioreactor configuration
      (fixed-bed reactor with immobilised Trametes versicolor or fluidised bed reactor
      with pellets of Trametes versicolor).

PMID- 16972381
TI  - Operational strategies for thermophilic anaerobic digestion of organic fraction
      of municipal solid waste in continuously stirred tank reactors.
AB  - Three operational strategies to reduce inhibition due to ammonia during
      thermophilic anaerobic digestion of source-sorted organic fraction of municipal
      solid waste (SS-OFMSW) rich in proteins were investigated. Feed was prepared by
      diluting SS-OFMSW (ratio of 1:4) with tap water or reactor process water with or
      without stripping ammonia. Three continuously stirred tank reactors were operated
      at 55 degrees C with 11.4 gVS d(-1) loading rate and 15 d retention time. Total
      ammonia nitrogen (TAN) level in the reactor fed with recirculated water alone was
      spiked to 3.5 and 5.5 g-N l(-1) through ammonium bicarbonate additions. Dilution
      of SS-OFMSW with fresh water showed a stable performance with volatile fatty
      acids of < 1g l(-1) and methane yield of 0.40 m3 kg(-1) volatile solids (VS). Use
      of recirculated process water after stripping ammonia showed even better
      performance with a methane yield of 0.43 m3 kg(-1) VS. Recirculation of process
      water alone on the other hand, resulted in process inhibition at both TAN levels
      of 3.5 and 5.5 g-N l(-1). However, after a short period, the process recovered
      and adapted to the tested TAN levels. Thus, use of recirculated process water
      after stripping ammonia would not only evade potential inhibition due to ammonia
      but could avoid the use of fresh water for dilution of high solids protein-rich
      SS-OFMSW.

PMID- 16972382
TI  - Carbon substrate utilisation profile of a high concentration effluent degrading
      microbial consortium.
AB  - This paper presents the carbon substrate utilisation profile of a group of
      microorganisms responsible for the biodegradation of a highly concentrated
      industrial effluent. A 1 litre bioreactor was used to study this consortium's
      biodegradation potential, with the chemical oxygen demand (COD) of the waste
      being reduced by 90% from 24000 mg l(-1) within 456 hours. This study also
      demonstrates that the consortium is capable of degrading organic solvents, such
      as isopropanol, at concentrations of 260 mg l(-1). The population distribution
      and biochemical behaviour were also characterised using denaturing gradient gel
      electrophoresis (DGGE) and Biolog Eco Plates at various stages of bioreactor
      operation. The DGGE results indicated that the dominant bands of the microbial
      population profile were stable at various operational stages, and that only a few
      bands varied with time. Moreover, four Biolog Eco plates were inoculated with
      samples drawn from the bioreactor at 0, 24, 72 and 120 hours after inoculation.
      Based on this Biolog Eco Plate profiling, a carbon source utilisation analysis
      was conducted to group the substrates according to their colour development
      patterns. Patterns were quantified via measurement of well optical density.
      Subsequently, cross-correlation statistical techniques were used to establish the
      existence of recurrent behavioural responses from each carbon source to the
      various wastewater samples. From the cross correlation, an attempt was made to
      classify the metabolic potential for future biodegradation processes.
      Carbohydrates, amino acids and carboxylic acids were the most predominant groups
      of sole carbon substrates showing similar growth behaviour in the consortium.

PMID- 16972383
TI  - Activated sludge diffusion for odour removal --effects of H2S on the biomass.
AB  - The removal of odours from wastewater treatment plants through diffusion of odour
      containing air volumes into the aerated basins was investigated in a bench scale
      experimental campaign which lasted more than 200 days. Hydrogen sulphide was
      selected as a model odorous compound and its removal efficiencies were
      experimentally evaluated along with its effects on the biomass and on the main
      biochemical processes. Two bench scale sequencing batch reactors were fed in
      parallel on real primary sewage and monitored for chemical oxygen demand removal,
      nitrification and denitrification. The balance of H2S was also monitored after
      adding to one of them a Na2S liquid solution of 17 mgS l(reactor)(-1) d(-1),
      corresponding to a gas-phase concentration of 240 mgS (Nm3)(-1). Results showed
      an average sulphide removal of 94% in the reactor supplied with Na2S. Moreover,
      microbial composition did not show relevant variations after the addition of
      sulphide, and the good features of activated sludge flocs were maintained also in
      terms of sludge settleability. No relevant effects of sulphide were detected on
      carbon and nitrogen metabolism and chemical oxygen demand removal, nitrification
      and denitrification efficiencies were always above 75%, 95%, and 50%
      respectively, and comparable across the two reactors.

PMID- 16972384
TI  - [Analysis and speciation of metals in sediments of an artificial water reserve in
      a mining zone the case of Guenitra Dam, Algeria].
AB  - The distribution of Cd, Pb, Zn, Mn and Fe was studied in the sediments of
      Guenitra reservoir located in a mining zone in the northeast of Algeria. An
      analytical procedure involving sequential chemical extractions was used for the
      partitioning of metals in the fractions: exchangeable, bound to carbonates, bound
      to iron and manganese hydroxides, bound to organic matter and bound to mineral
      structures. Experimental results obtained, show that the metals investigated are
      distributed in all the compartments of the sediments. Except for iron, the
      quantity of each metal associated with the available fractions exceeded 70% of
      the total quantity. Cd and Zn mostly occurred in the oxidisable fraction and the
      hydroxide bound fraction dominated in the case of Pb.

PMID- 16972385
TI  - Start-up of a biological sequencing batch reactor to treat supernatant from
      anaerobic sludge digester.
AB  - Treating the supernatant (reject water) from an anaerobic sludge digestion (800
      1200 mg NH4(+)-N l(-1)) may be a good solution for meeting local requirements. As
      reject water represents 0.6% of the total wastewater influent flow and contains
      10-30% of the total N it is recirculated to the head plant. In this study, a lab
      scale start-up of biological nitrification/denitrification process to treat
      reject water was developed in a sequencing batch reactor. Sludge acclimation to
      the denitrification process was quite fast (6-7 days) for both NO2(-)-N and NO3(
      )-N, whereas in nitrification it was slower (20 days). The use of a sequencing
      batch reactor to treat reject water produced a complete biological reduction of
      the NH4(+)-N via nitrite, working with sludge age of 15 days, hydraulic retention
      time of 1.3 days, temperature of 28 degrees C, pH between 7-8.5 and biomass
      concentration around 3500 mg VSS l(-1). Specific efficiencies were 14 mg NH4(+)-N
      (g VSS h(-1)) and 30 mg NO2(-)-N (g VSS h)(-1).

PMID- 16972386
TI  - Effect of feed length on settleability, substrate uptake and storage in a
      sequencing batch reactor treating an industrial wastewater.
AB  - The paper compares the performance of two Sequencing Batch Reactors (SBRs)
      treating the same industrial wastewater (composed of formic acid, ethylene glycol
      and methanol) operated at two different lengths of the feed. The two SBRs were
      operated in parallel under the same conditions of organic load (0.85 gCOD l(-1)
      d(-1)) and sludge age (about 10 d), the only difference being the length of the
      feed: less than 1 min vs. 5 h. In this way the conditions of a plug flow reactor
      and of a completely mixed reactor were simulated. The two systems were compared
      on sludge settleability (related to filaments abundance and floc morphology),
      substrate uptake rates and polyhydroxyalkanoates (PHAs) storage rates. The main
      difference between the two systems was in the settling properties of the sludge:
      both SVI and effluent solids were higher in the system with slow feed. With
      regard to filamentous microorganisms, even though both reactors were inoculated
      with the same sludge with high concentration of filaments, they were rapidly
      washed out from both systems. Microscopic observations showed that the reason for
      the different settling properties of the two sludges was in the floc structure,
      which was more compact in the system operated with fast feed. These data support
      the theory of the role of diffusion inside the flocs in determining the settling
      properties of the sludge. The maximum substrate uptake rates and PHA storage
      rates were similar in the two systems, showing that also the microorganisms grown
      at a constant and low substrate concentration were able to quickly increase their
      activity and to store PHAs when in the presence of a sudden change in substrate
      concentration.

PMID- 16972387
TI  - Treatment of ballast water; how to test a system with a modular concept?
AB  - A variety of methods were successfully applied to examine the efficacy of a
      modular ballast water system according to the standards as adopted by the
      International Maritime Organization. The ballast water treatment system had a
      capacity of 530 m3 h(-1) consisted of a pump system, a hydrocyclone, a 50 microm
      mesh-size self-cleaning filter and an installation for the addition of a chemical
      disinfectant (PERACLEAN Ocean). The land-based testing facility used natural sea
      water of high turbidity during the spring phytoplankton bloom. The
      mesozooplankton fraction was inspected with a standard binocular. Larger
      zooplankton were effectively removed with the filter; the smaller sized fraction
      containing larvae and nauplia were killed after chemical treatment. The
      phytoplankton component was monitored using flow cytometry. The huge colonies of
      the phytoplankton Phaeocystis globosa were disrupted in the hydrocyclone
      liberating the colony cells which passed as single cells through the filter.
      These cells remained viable but were finally killed in the secondary (chemical)
      step. Bacteria also passed all mechanical treatment steps unharmed but were
      killed in the final step. Viability tests with SYTOX Green, which were
      specifically designed for phytoplankton, showed that mechanical treatment did not
      affect the percentage of viable cells a short-term, but after several hours the
      viable cell counts dropped down to 70%. Phytoplankton cells recovered within a
      single day and formed a new dense bloom rapidly. The bacteriostatic component of
      the chemical disinfectant (H2O2) remained present for several days preventing
      regrowth of bacteria for up to 15 days after addition. In conclusion, the IMO
      standards were met using the modular ballast water treatment unit and the applied
      instruments and assays were effective and rapid tools to qualify and quantify the
      organisms present as well as their viability.

PMID- 16972388
TI  - Uptake of molybdate by adsorption onto industrial solid waste Fe(III)/Cr(III)
      hydroxide: kinetic and equilibrium studies.
AB  - Removal of molybdate on to industrial solid waste Fe(III)/Cr(III) hydroxide as
      adsorbent has been investigated. Pretreated adsorbent was found to be more
      efficient in the uptake of molybdate compared to untreated adsorbent. Effect of
      pH on the adsorption was studied in the pH range 4.0 to 10.0. Optimum pH for
      maximum removal was found to be 4.0. Langmuir and Freundlich isotherm models were
      used to study the adsorption capacity of the adsorbent. The adsorption follows
      second order kinetics. No significant effect of temperature has been observed.
      Desorption studies showed that ion exchange mechanism is predominant.

PMID- 16972389
TI  - [Survey of the cycle of reproduction of red algae Gelidium sesquipedale (Turner)
      Thuret (case of the maritime zone of El Jadida-Jarf lasfer of Morocco)].
AB  - The industrial exploitation of the agarophyte, Gelidium sesquipedale, is an
      important part of the economy of Morocco, however the species is in danger of
      being overexploited. The development of research on the biological cycle of the
      species enbles a better understanding of environmental influencies on its
      reproduction periods and of the effect of pulling up on the growth of the thalli.
      This should assist in helping to avoid excessive collection of the species and to
      reinforce a period of rest where no collection takes place. The major are of
      collection supplying industries is the maritime sector of El Jadida - Jarf
      Lasfar. In order to study the methods of reproduction of G sesquipedale, a first
      series of experimentation was carried out by the INRH. Studies relating to
      biology and the effect of pulling up on the biometrics of the thalli of this
      species were carried out at two stations of the maritime zone El Jadida - Jarf
      lasfar: Moulay Abdellah and Sidi Bouzid during the period 2000-2002. The results
      obtained show that the fertile thalli are present all the year with a maximum
      reproductive activity in winter. The recruitment of the young slings takes place
      before the winter and occurs more in Sidi Bouzid. The regeneration and the growth
      of the thalli are carried out in spring and summer. To preserve this resource, it
      is necessary to put in place a system whereby one zone or area is allowed to rest
      whilst another area is cultivated for a year; whilst in the following year the
      rercise occurs.

PMID- 16972390
TI  - Review of the extrinsic stain removal and enamel/dentine abrasion by a calcium
      carbonate and perlite containing whitening toothpaste.
AB  - There has been an increase in the demand from consumers and patients for products
      that whiten teeth. To meet this demand, a whitening toothpaste containing calcium
      carbonate and perlite as the abrasive system and an efficacious fluoride source
      has recently been launched. The aim of the current paper is to review the
      toothpaste's stain removal efficacy and its effects on enamel and dentine wear.
      It has been shown to be effective at removing model extrinsic stain in vitro.
      Further, it has been shown to be more effective in removing naturally occurring
      extrinsic tooth stain than a silica non-whitening control toothpaste after two
      weeks of twice daily brushing in a parallel group, double-blind clinical study
      using 152 adult volunteers. In addition, the enhanced whitening effect did not
      give a clinically relevant level of wear to enamel or a significant increase in
      dentine wear compared to marketed non-whitening toothpaste formulations, as shown
      by using an in situ type model with ex vivo brushing.

PMID- 16972391
TI  - Tooth surface loss in adult subjects attending a university dental clinic in
      Trinidad.
AB  - OBJECTIVES: To determine the prevalence of tooth surface loss (TSL) in a sample
      of subjects attending a university dental clinic in Trinidad and to investigate
      the relationship to tooth brushing, medical history, parafunction and dietary
      habits. DESIGN: Tooth surface loss was measured clinically by the index used in
      the 1998 UK, Adult Dental Health Survey. SETTING: Trinidad, West Indies.
      PARTICIPANTS: Convenience sample of adult subjects attending The University of
      the West Indies Dental School Polyclinic, Mount Hope. METHODS: A questionnaire
      was administered and tooth surface loss measured clinically. MAIN OUTCOME
      MEASURES: mild, moderate and severe tooth surface loss. RESULTS: 155 subjects
      were examined (mean age 40.6 years) of whom 72% had some degree of TSL with the
      majority (52%), exhibiting mild, 16% with moderate and 4% with severe TSL. There
      were associations found between TSL and age (OR=3.14), reflux (OR=1.37),
      parafunction (OR=1.06), weekly consumption of citrus fruits (OR=1.31) and soft
      drinks (OR=1.78), daily consumption of alcohol (OR=1.40) and a vegetarian diet
      (OR=2.79). CONCLUSIONS: Tooth surface loss in this Trinidadian population group
      appears to be common. Data supports an association between TSL and age, reflux
      parafunction and certain dietary patterns.

PMID- 16972392
TI  - Attitudes of general dental practitioners in Europe to the microbial risk
      associated with dental unit water systems.
AB  - Dental Unit Water Systems (DUWS) are used in dental practices to provide water
      for cooling of dental equipment and irrigation of the oral cavity. However, they
      have been demonstrated to be contaminated with micro-organisms. There are
      currently no European Union (EU) Commission guidelines for the microbial quality
      of water discharged by DUWS. This study was part of an EU research programme to
      investigate the microbial contamination of DUWS in general dental practice (GDP)
      in the UK, Denmark, Germany, The Netherlands, Ireland, Greece and Spain.
      OBJECTIVE: To undertake a questionnaire survey on the type of DUWS in use and
      determine the attitude of GDPs to the risk of microbial infection from DUWS.
      MATERIALS AND METHODS: The questionnaire was written and translated into the
      language of each country before being posted to each participating dentist.
      Dentists were asked to complete the questionnaire survey and return it by post.
      RESULTS AND CONCLUSIONS: The major findings were that the majority of dentists
      did not clean, disinfect or determine the microbial load of their DUWS, and that
      dentists would welcome regular monitoring and advice on maintaining their DUWS;
      the introduction of guidelines; and recommendations on controlling the microbial
      load of DUWS.

PMID- 16972393
TI  - Gains in oral health and improved quality of life of 12-13-year-old Nepali
      schoolchildren: outcomes of an advocacy project to fluoridate toothpaste.
AB  - OBJECTIVES: To report on gains in oral health and improved quality of life of 12
      13-year-old Nepali schoolchildren five and six years after the introduction of
      fluoride toothpaste in 1999. DESIGN: Cross sectional baseline surveys in 1999 and
      2001, and follow up surveys in 2004 and 2005 were multi-stage cluster sampling in
      design. SETTING: Urban and rural schools in Central, Far Western, Mid Western and
      Western Developmental Regions of Nepal. PARTICIPANTS: 2,770, 12-13-year-olds in
      1999 and 1,001, 12-13-year-olds in 2004 were examined regionally. 637 12-13-year
      olds from Kathmandu valley and 448 12-13-year-olds from Tansen municipality were
      examined in 1999. The same schools in Kathmandu valley and Tansen were visited in
      2005 and 761 and 482 12-13-years from Kathmandu valley and Tansen were examined.
      6,064 8-15-year-olds in 2001 and 1,001 12-13-year-olds in 2004 participated in
      the collection of information on oral hygiene practice and quality of life.
      METHOD: Examinations were carried out by trained and calibrated examiners using
      the WHO diagnostic criteria for caries and questionnaires were interview
      administered by trained interviewers. INTERVENTION: Advocacy for fluoride
      toothpaste between 1997 and 2002. RESULTS: There was a 26.6% decline in caries
      prevalence and 38.0% decrease in 12-13-year old DMFT from 1999 to 2004 throughout
      four of five regions of Nepal. Approximately 65-75% of the 12-13-year-olds used
      fluoride toothpaste from 1999 to 2004. School specific data reveals a reduction
      in DMFT of 43.8% in Tansen and 53.6% in the Kathmandu valley from 1999 to 2005.
      From 2001 to 2004, report of oral pain decreased by 10%. CONCLUSIONS: The most
      likely reason for the decline in dental caries and reduction in oral pain is the
      widespread consumption of fluoride toothpaste by the 12-13-year-old
      schoolchildren.

PMID- 16972394
TI  - Identification of dental implants through the use of Implant Recognition Software
      (IRS).
AB  - AIM: To develop computer software to allow general dental practitioners and
      others to identify unidentified implants in patients' mouths using a range of
      criteria. METHODS: Internet searches for implant manufacturing companies
      worldwide in all languages using terms: dental implants, dental implant
      manufacturers and dental implant companies. Once identified, all relevant
      information including images regarding dental implant products was collected even
      that for discontinued products. A program was then devised using key design
      factors to enable identification of individual implants. RESULTS: The searches
      produced details for 87 implant manufacturers based in 21 countries with 231
      different implant designs. The resultant program has been successfully trialled
      and used in both general dental practice and for forensic identification.
      CONCLUSION: The program developed provides a valuable adjunct to the
      identification of implant systems present in patients' mouths.

PMID- 16972395
TI  - Percutaneous injuries of dental personnel at the University of the West Indies,
      School of Dentistry.
AB  - AIM: To report the results of a survey of all percutaneous injuries occurring in
      2003-2004 to staff and students at the dental school in Trinidad. METHOD: Data
      were collected via 163 questionnaires administered to all dental surgery
      assistants, the current clinical students (years 3, 4 & 5), the interns, part
      time and full-time academic staff. RESULTS: A 71% response rate was obtained. The
      number of persons reporting one or more sharps injuries at the dental school was
      42 (37%). Of these, 17 (40%) were percutaneous. Needlesticks and periodontal
      scaler injuries were the most common. There was no significant correlation
      (p>0.05) between injury and gender, age group, dominant hand or needle recapping
      technique. 75% of respondents described their concern of contracting a blood
      borne disease from a sharps injury as "high" and 59% of the respondents followed
      the school's recommended protocol following the injury. 50% of the injuries among
      the students and interns were not reported. CONCLUSIONS: A more rigorous
      programme of risk management with respect to sharps injuries needs to be designed
      and implemented at the school. There is also a need to improve surveillance of
      and reduce the underreporting of these injuries.

PMID- 16972396
TI  - Trends in service provision among Australian private general dental practitioners
      over a 20-year period.
AB  - AIM: To-investigate time trends in service provision. DESIGN: Five cross
      sectional surveys across a 20-year period. SETTING: Australian private general
      practice PARTICIPANTS: A random sample of dentists. METHODS: Mailed
      questionnaires were collected in 1983, 1988, 1993, 1998 and 2003 (response rates
      71%-76%). MAIN OUTCOME MEASURES: Services per visit, annual services per dentist;
      annual services per patient. RESULTS: Total services per visit increased over the
      study period from 1.78 to 2.37 (Poisson regression; P<0.05). However the annual
      number of services provided per dentist did not vary significantly, reflecting a
      trend among dentists to supply fewer patient visits per year. The annual number
      of services provided per patient increased from 3.47 to 5.50 (OLS regression;
      P<0.05), reflecting both increased service rates per visit and increased numbers
      of visits by patients. Dentists provided less restorative, prosthodontic and
      extraction services per year, but more diagnostic, preventive, endodontic and
      crown and bridge services. The annual care received per patient also included
      more diagnostic, preventive, endodontic and crown and bridge services but
      differed from the dentist pattern through increased rates of restorative services
      over the study period. CONCLUSIONS: The content of dentist workloads has changed
      to include less emphasis on removal and replacement of teeth and more effort on
      diagnosis and prevention aimed at retention of natural dentitions.

PMID- 16972397
TI  - The responsibilities and rights of dental professionals 3. Professional rights.
AB  - Professional status, professional autonomy, clinical freedom, self-regulation and
      the right to serve patients and the community seem to be the main rights of
      dentists. Although they simply may be seen as privileges that are related to
      being a dentist, these rights cannot be considered independent from dentists'
      roles and responsibilities. They are, in fact, valuable tools that serve dentists
      to meet their broad responsibilities that arise from the 'social contract'
      between the profession and the public.

PMID- 16972398
TI  - The oral microflora--friend or foe? Can we decide?
AB  - This paper discusses the factors that determine whether the oral microflora play
      a beneficial or detrimental role in the health of an individual during their
      life. The resident microflora of the mouth is diverse, and distinct from that
      found elsewhere in the body due to its unique biological and physical properties.
      This natural microflora is essential for the normal development of the physiology
      of the host, and contributes to the host defences by excluding exogenous micro
      organisms. The oral microflora varies in composition on distinct surfaces (e.g.
      teeth, mucosa), and at sites on a specific surface (e.g. fissures, gingival
      crevice), demonstrating that subtle properties of a habitat influence the ability
      of individual species to colonise and dominate. The composition of these oral
      microbial communities remains relatively stable over time (microbial
      homeostasis). This stability does not indicate a passive relationship with the
      host, but reflects a dynamic balance among the component species. However, this
      stability can be perturbed by significant changes to the oral environment or in a
      person's life-style that occur during the life of an individual. Alterations in
      diet, medication, smoking, saliva flow, denture wearing, general health, etc, can
      lead to overgrowth by previously minor components of the oral microflora, which
      can predispose a site to disease. Likewise, the immune response can wane in old
      age, which may result in colonisation by exogenous and often pathogenic micro
      organisms. Oral micro-organisms can also act as opportunistic pathogens, and
      cause serious disease elsewhere in the body. Therefore, active oral health care
      management is needed in order to maintain microbial homeostasis throughout life
      to ensure that we reap the benefits of our resident oral bacteria and not suffer
      from their mischief.

PMID- 16972399
TI  - What has ageing to do with periodontal health and disease?
AB  - Periodontitis is a multi-factorial disease and in most cases also a disease with
      a chronic progression. Exposure to factors which contribute to periodontitis
      occurs over a long period, so that at the time of diagnosis it may be difficult
      to identify and evaluate what co-factors have contributed to its development.
      These include exposure to bacteria and viruses, inflammation, genetic factors,
      health behaviours and a variety of social factors, socio-economic status,
      behavioural and nutritional habits, the ability to cope with stress and the
      ability of the immune system to fight infections. Many patients in their 50s also
      experience other conditions such as heart disease, diabetes mellitus, or
      rheumatoid arthritis and recent reports on the associations and potential
      biological mechanisms by which periodontitis can be linked to other systemic
      diseases suggest that the patient with periodontitis is a challenged individual.
      Neither individuals nor their oral health care providers are currently prepared
      for the challenges in oral health care as the expectation of successful ageing
      with remaining and aesthetically functional teeth is increasing. The scientific
      evidence is, however, growing, and while the opportunities to prepare for
      successful ageing exist they must be included in the educational process of both
      current and future oral health care providers and their patients.

PMID- 16972400
TI  - Reconstructive periodontal surgery: a challenge for modern periodontology.
AB  - The overall rationale for the proposed clinical approach in this paper comes from
      consideration of different regenerative approaches reported in the literature.
      The protocol proposed is based mainly on evidence and partly on the clinical
      experience of the author and co-workers, who have found that patient associated
      factors such as plaque control, residual periodontal infection, and smoking
      habits are those of particular relevance. Among the technical/surgical associated
      factors, lack of primary closure of the interdental space and consequent
      bacterial contamination of the regenerating wound represent the most significant
      factors leading to compromised outcomes. Modified flap designs and a
      microsurgical approach have been shown to improve the outcomes. There is now
      sufficient evidence to suggest that clinicians can incorporate periodontal
      regeneration in their surgical armamentarium. Periodontal regeneration can be
      predictably used to treat deep pockets associated with deep intrabony defects in
      young and old people, aimed at pocket/defect resolution with aesthetic
      preservation, gain of clinical attachment and bone.

PMID- 16972401
TI  - Periodontal infections and atherosclerotic vascular disease: an update.
AB  - The role of periodontal infections as a putative risk factor for atherosclerotic
      vascular disease (ASVD) has been reported in the literature over the past decade.
      This review provides insights into biologically plausible pathways that can
      potentially mediate such an association, and discusses recent findings from
      epidemiological studies and intervention trials. Accumulating epidemiological
      evidence suggests that clinical, microbiological and serological markers of
      periodontal infection are associated with subclinical and manifest ASVD. Early
      evidence from intervention studies suggests that the control of periodontal
      infections may result in improved levels of markers of systemic inflammation and
      measures of endothelial dysfunction. The extent to which the control of
      periodontal infections results in lower incidence of ASVD events is logistically
      difficult to assess and has not been addressed in any study so far.

PMID- 16972402
TI  - [Clinical characteristics and results of surgical treatment of petroclival
      meningioma].
AB  - INTRODUCTION: The size of meningioma and its relation with neurovascular
      structures in petroclival region stipulate the degree of surgical radicalism and
      determine an operation risk. In spite of progress of surgical technology, the
      rate of surgical morbidity in view of cranial nerves deficit is 30%-50%.
      OBJECTIVE: The objective of our study was to present the results of treatment of
      patients with petroclival meningiomas and to point to correlation of preoperative
      radiological findings and intraoperative results as well as neurological status
      of patients before and after surgical treatment. METHOD: Retrospective analysis
      of 35 operated petroclival meningiomas at the Institute of Neurosurgery, CCS, in
      the period from 1995 to 2004 was presented. The following parameters were
      analyzed: size of tumor, relation with bone and neurovascular structures,
      preoperative condition, degree of surgical radicalism and postoperative outcome.
      RESULTS: The size of tumor was classified in four groups. There were 20 tumors at
      the right, and 15 at the left side. At the time of diagnostic procedures (based
      on CT and MRI), 20 tumors were in contact with brainstem, 9 compressed the
      brainstem, and 6 obstructed the IV ventricle. Preoperative patient condition was
      evaluated by Karnofsky index. Mean value for group I was 90, II - 80, III - 70
      and IV - 50. In 9 cases, liquor drainage was performed preoperatively. In 3
      cases, external liquor drainage was carried out postoperatively, and in one case
      it was replaced by permanent liquor drainage. Radical operation was performed in
      44%, and significant reduction was done in other cases. In the postoperative
      period, 11% patients died, 28% had cranial nerves deficit, and pyramid deficit
      was recorded in 14% of the patients. The tumor size (III-IV) and brainstem
      compression were found to be statistically significant (p<0.05) as predisposed
      factors of deficit prolongation. CONCLUSION: Petroclival meningoma surgery is
      required upon precise preoperative analysis. Radicalism of operation is reserved
      for small and medium tumors, younger patients, and patients in good preoperative
      condition

PMID- 16972403
TI  - [Surgical treatment of eye injuries in five-year survey period].
AB  - INTRODUCTION: Eye injuries represent one of the biggest problems in eye surgery
      all around the world, including our country. Treatment of eye injuries demands
      highly skilled personnel and adequate technical equipment. OBJECTIVE: To show a
      total number of eye injuries, including the surgical methods used for their
      treatment. METHODS: In our study, retrospective analysis of all performed
      surgical methods used in treatment of hospitalized patients in our Clinic during
      2000-2004 was carried out. A special attention was paid to pars plana vitrectomy,
      together with combined anterior-posterior segment procedures. RESULTS: During
      2000-2004, a total of 347 pars plana vitrectomy, and 27 traumatic retinal
      detachments (conventional methods) were performed. In addition, 314 patients with
      contusion trauma of the eyes were treated. Out of 297 patients with penetrant eye
      injuries, 196 (66%) had intraocular foreign bodies (IOFB), and 101 (34%) were
      without IOFB. A total number of endophthalmitis was 34 (8.73%). The number of
      combined anterior-posterior segment operations during this period was 227.
      CONCLUSION: Vitreoretinal operations are the most prevailing in treatment of
      serious eye injuries. Pars plana vitrectomy is also the most common method of
      surgical treatment of eye injuries.

PMID- 16972404
TI  - [Oral surgery as risk factor of odontogenic maxillary sinusitis].
AB  - In order to determine the risk factors of odontogenic maxillary sinusitis, a
      total number of 40 patients with this pathological condition was examined in
      three-year period. Oroantral communication was detected in 40% of patients,
      oroantral fistula in 25%, sinus foreign bodies in 15% and other pathological
      conditions in 10% of cases. The extraction of the upper lateral teeth was the
      cause of odontogenic sinusitis in 65% patients. Given the specific tooth, the
      first upper molar was the most common cause of the condition, i.e. in 40% of
      cases. It may be concluded that odontogenic sinusitis is the complication of the
      oral cavity surgery in 85% of patients, what should be taken into consideration
      in prevention.

PMID- 16972405
TI  - [Significance of fine-needle aspiration biopsy of peripheral lymph nodes upon the
      initial presentation of patients with lymphadenopathy of unknown etiology].
AB  - Fine-needle aspiration biopsy is safe, simple, cost-effective and efficient
      technique providing rapid information and, therefore, directing further approach
      to a patient. Its findings are especially beneficial for verification of lymphoid
      origin of the enlarged growth, diagnostics and differentiation of metastatic,
      infectious, reactive and lymphomatous conditions; determination of the extent of
      tumor; detection of recurrence; monitoring of the course of disease; obtaining of
      material for special studies such as microbiological cultures, immunological or
      genetic studies as well as electron microscopy; in addition, for encouragement of
      patient in case of benign nature of the disease. At the Institute of Hematology,
      in three-year period, a total of 193 fine-needle aspiration biopsies were
      performed in 172 patients with the enlarged peripheral lymph nodes. Technically,
      aspiration biopsy was successful in 175/193 attempted interventions (91%).
      Punctates were analyzed by cytomorphology and subsequently compared with
      histopathological findings. In indistinguishable cases, additional
      immunocytochemical streptavidin-biotin peroxidase staining was carried out. In
      our studies, immunocytochemical analysis was performed in 63 out of 81 patients
      (78%), and diagnostic accuracy was 93.6% what was compatible with the results of
      other authors. It significantly corrected the earlier cytomorphological
      histological congruence that used to be 83%. Immunocytochemistry has contributed
      to diagnostic value of cytological analysis of punctate, before all, in view of
      its higher diagnostic accuracy, which, according to majority of authors, is about
      90%.

PMID- 16972406
TI  - [Acute appendicitis in the first three years of life].
AB  - Acute appendicitis is the most frequent disease in children population that
      requires an urgent surgical intervention. Only 2% of operated children belong to
      the group younger than 3 years. Yet, 77% are school children. Appendicitis in
      young children is characterized by: atypical clinical course, late diagnosis,
      high percentage of perforations, and high level of mortality and morbidity rates.
      The commonest symptoms are: vomiting, undefined abdominal pain, and high
      temperature. Abdominal distention and diffuse abdominal tenderness are the most
      frequent signs during examination. Our analysis (1991-2000) included all patients
      younger than 3 years who were hospitalized in Clinic for Pediatric Surgery Nis
      with diagnosis of the acute appendicitis. Out of 2533 patients with disease, 58
      (2.3%) were younger than 3 years, 23 were girls (39.7%) and 35 were boys (60.3%).
      Perforated appendicitis was found in 55 (94.8%) of 58 children. Thirty five
      (60.5%) patients were previously treated. Complications developed in 36 (62.1%)
      cases: purulence (58.3%), dehiscence (22.3%), abdominal wall abscess (13.8%), and
      ileus (5.6%). Acute appendicitis is very specific condition that needs high
      attention by all doctors engaged in pediatric health care. Our recommendation is
      "to admit and observe" by using the physical examination in all suspected cases.
      Sometimes, even sedation may be used for better palpation results.

PMID- 16972407
TI  - [Reverse Trendelenburg's position vs. supine-horizontal position for induction of
      general anesthesia in obese neurosurgical patients].
AB  - INTRODUCTION: The induction of general endotracheal anesthesia (GETA) is
      associated with variable period of apnea. Obese patients have reduced oxygen
      supply during period of apnea. Hypoxemia and subsequent hypercarbia, during
      period of apnea, are strong stimuli of cerebral blood flow and intracranial
      pressure increase. OBJECTIVE: The objective of our study was to determine the
      patient position with safe apnea period (SAP), which will minimize the risk of
      hypoxemia, as an optimal positioning for induction of GETA in obese neurosurgical
      patients. METHOD: Obese patients (BMI > 30kg m(-2)) were randomly placed to one
      of two positions for induction of GETA: group I (n=20) consisted of patients
      assuming 30 degree reverse Trendelenburg's position; group II (n=20) was in
      supine-horizontal position. After the arterial oxygen saturation of 100% measured
      by pulse oximetry (SpO2), patients were allowed to remain apneic. The time
      required for SpO2 to decline from 100% to 94% was recorded as SAP. The lowest
      SpO2 after restoration of ventilation and recovery time to 98% SpO2 were also
      recorded. RESULTS Time needed for SpO2 to decline to 94% was: 196.9 +/- 21.53 sec
      in group I, and 130.65 +/- 25.73 sec in group II. There was significant
      difference between groups (I vs. II; p < 0.05). SpO2 of patients in the reverse
      Trendelenburg's position dropped the least and took the shortest time to restore
      to 98%. The recovery time was much longer in group II, 132.65 +/- 33.75 (I vs.
      II; p < 0.05). CONCLUSION: 30 degree reverse Trendelenburg's position provides
      longer SAP when compared with horizontal-supine positions. This extra time may
      preclude adverse sequelae resulting from hypoxemia during induction of obese
      neurosurgical patients.

PMID- 16972409
TI  - [Analysis of the effect of diabetes type 2 duration on beta cell secretory
      function and insulin resistance].
AB  - Diabetes type 2 is a chronic metabolic disorder. Pathogenesis of diabetes type 2
      results from the impaired insulin secretion, impaired insulin action and
      increased endogenous glucose production. Diabetes evolves through several phases
      characterized by qualitative and quantitative changes of beta cell secretory
      function. The aim of our study was to analyze the impact of diabetes duration on
      beta cell secretory function and insulin resistance. The results indicated
      significant negative correlation of diabetes duration and fasting insulinemia, as
      well as beta cell secretory function assessed by HOMA beta index. Our study also
      found significant negative correlation of diabetes duration and insulin
      resistance assessed by HOMA IR index. Significant positive correlation was
      established between beta cell secretory capacity (fasting insulinemia and HOMA
      beta) and insulin resistance assessed by HOMA IR index, independently of diabetes
      duration. These results indicate that: beta cell secretory capacity, assessed by
      HOMA beta index, significantly decreases with diabetes duration. In parallel with
      decrease of fasting insulinemia, reduction of insulin resistance assessed by HOMA
      IR index was found as well.

PMID- 16972408
TI  - [Expression of Fas and Fas-L in renal cell carcinoma].
AB  - INTRODUCTION: The previous investigations revealed that Fas-L expression on tumor
      cells can be one of the reasons of tumor growth, or tumor regression, with or
      without activation of the immune response. OBJECTIVE: The objective of our study
      was to investigate the expression of Fas and Fas-L in situ in normal human renal
      tissue as well as in different types of renal cell carcinoma (RCC) according to
      tumor grading. METHOD: Expression of Fas and Fas-L was examined in 25 RCCs
      classified according to nuclear grades: G1-G3 and to cell type: 17 clear cells, 3
      chromophilics (2 eosinophilics, 1 basophilic), 2 chromophobes and 3 spindle
      cells. Ten normal human kidneys were analyzed, too. Indirect immunoperoxidase
      technique was applied. Spread and intensity of staining of Fas and Fas-L
      molecules expression were scored semiquantitatively. RESULTS: Distribution of Fas
      expression in these RCC was typically diffuse. However, Fas-L was almost
      completely absent in clear cell RCC. In 3 clear cell RCC, some tumor stromal
      cells exhibited strong expression of Fas-L. On the contrary, chromophilic,
      chromophobe and spindle cell RCCs grading from G2-G3, manifested variable
      combinations of Fas and Fas-L expression. CONCLUSION: The most of clear cell type
      low grade RCCs manifested intensive and extensive expression of Fas and
      completely absence of Fas-L. However, RCCs of high grade malignancy belonging to
      the clear cell, eosinophilic, chromophobe or spindle cell types can have various
      combinations of Fas and Fas-L expression. It may probably lead to development of
      different mechanisms of avoidance of immune response to RCC.

PMID- 16972410
TI  - [The outpatient use of beta lactam antibiotics in Montenegro before the
      introduction of new reform strategy on drug market].
AB  - INTRODUCTION: The study represents the first investigation of outpatient use of
      beta lactam antibiotics in Montenegro carried out in accordance with
      internationally approved methodology (DDD/ATC). OBJECTIVE: The objective of our
      study was to establish both the scope and overall use of beta lactam antibiotics,
      and to assess their compatibility with current pharmacotherapeutic guidelines and
      their use in developed countries. METHODS: The retrospective pharmaco
      epidemiological study comprised a 100%-sample of beta lactams that were used in
      the period prior to introduction of new reform strategy on drug market. RESULTS:
      Beta lactam antibiotics (J01C, J01D) were the most frequently applied anti
      infectives for systemic use (ATC group J) in 2000 (11.3 DDD/1000 inh./day, 61%).
      Penicillins (J01C) were the most utilized (8.0 DDD/1000 inh./day, 71%).
      Cephalosporin derivatives (cephalexin and cefaclor) accounted for the remaining
      29% (3.3 DDD/1000 inh./day). Aminopenicillins were prevailing among penicillins
      (85%). Beta lactamase sensitive penicillins were in the second place and
      approximately accounted for 14%. CONCLUSION: The results of our study showed that
      the use of beta lactam antibacterials could be estimated as partially
      satisfactory. There is a need to make additional efforts with a view of further
      rationalization.

PMID- 16972411
TI  - [The prevalence study of hospital-acquired infections at different surgical
      departments in Banjaluka].
AB  - INTRODUCTION: Prevalence study is simple, cheap and fast method that provides
      information about hospital-acquired infections (HAI). OBJECTIVE: To assess the
      HAI prevalence at different surgical departments in the Clinical Center of
      Banjaluka. METHOD: A point prevalence study design was used. All patients (N =
      174) hospitalized on July, 1st, 1999 were included in the study. The study was
      performed by following the CDC guidelines. All patients with clinically
      manifested infections on the day of study in all surgical departments were
      recorded. infections of more than one site in the same patient were considered
      separate infections. RESULTS: The overall prevalence of patients with HAI was
      16.1% (28/174; 95%CI = 10.4-21.6) and the overall HAI prevalence was 18.4%
      (32/174). Surgical-site infections were the most prevalent (6.3%) followed by
      skin/soft tissue infections (4.6%) and urinary tract infections (4.0%). More than
      two thirds (87.5%) of HAI were microbiologically documented. The most commonly
      isolated microorganisms were Pseudomonas aeruginosa (29.7%), Enterobacter spp.
      (24.3%) and Staphylococcus aureus (16.2%). CONCLUSION: This point prevalence
      study clearly showed the magnitude of HAI problem at different surgical
      departments in the Clinical Center of Banjaluka, the most prevalent anatomic
      localizations of HAI, and the most common causes.

PMID- 16972412
TI  - [Total atmospheric ozone column above the territory of Serbia and Montenegro].
AB  - INTRODUCTION: Atmospheric ozone attenuates ultraviolet radiation reaching the
      Earth's surface. Since UV-B radiation is considered the principal factor of
      causing the skin cancers, cataracts and some immunological disorders,
      determination of total ozone column has become everyday practice. In Serbia and
      Montenegro, such determinations are not being done. Satellite data for the entire
      globe are accessible. OBJECTIVE: The objective of our work was to collect and
      analyze data for the territory of Serbia and Montenegro, because ozone is an
      important parameter for the study of effects and protection from UV radiation.
      METHODS: Data collected during TOMS (Total Ozone Measuring Spectrometer)
      experiment are presented for grid whose elements are 1 degrees latitude by 1.25
      degrees longitude. Grid elements in which the territory of Serbia and Montenegro
      comprises more than 50% of the element area were taken to represent the territory
      of Serbia and Montenegro. Eleven grid elements were selected and average monthly
      values for 272 months in the period from 1978 until 2004 were collected. Data for
      the period between 1993 and 1996 were unavailable. RESULTS: Mean values of total
      ozone column and mean monthly values of eleven grid elements differed very
      little. Differences were smaller than magnitudes of random error. Average annual
      values of total ozone column above the territory of Serbia and Montenegro were in
      the range from 316 Dobson units (DU) in 2002 to 347 DU in 1981. Annual cyclic
      changes of total ozone column showed spring maxima and autumn minima. Maximal
      recorded monthly value was 421 DU in March 1987 and minimal monthly value was 271
      DU in October 2001. There was a trend of decreasing total ozone column values in
      the period between 1979 and 1992 at the rate of approximately 4.5% per decade.
      CONCLUSION: Mean total ozone column value above the territory of Serbia and
      Montenegro can represent total ozone column for the whole territory. Annual
      cycles with spring maxima and autumn minima are in accordance with oscillations
      observed for middle northern latitudes. The trend showing 4.5% decrease per
      decade in the period between 1979 and 1992 corresponds well to trends calculated
      for comparable locations.

PMID- 16972413
TI  - [Work ability evaluation in neurosarcoidosis--a case report].
AB  - Sarcoidosis is a multisystemic granulomatous disease of unknown etiology which
      affects most frequently the hilar lymph nodes and lungs. Symptomatic involvement
      of the central nervous system may develop in patients diagnosed with sarcoidosis
      or it may be the initial manifestation of the disease. This is a case report of
      48-year old female patient admitted to our clinic for evaluation of working
      ability. The patient had a total of 24 years of service and occupational exposure
      and she has been employed as supplies procurement officer. On admission, she
      complained of the following discomforts: eye-lid pain, intellectual fatigue,
      psychic uneasiness, forgetfulness, dyspnea and productive cough. Neurological
      findings indicated the presence of the right eye ophthalmoplegia, psychoorganic
      syndrome and neurosarcoidosis. Ophthalmological examination evidenced bilateral
      ptosis and presence of anisocoria. Magnetic resonance imaging revealed discrete
      focal lesions of the pons (paracentral left) and parietal corona radiata of the
      left hemisphere. Based on performed examinations and diagnostics procedures,
      final evaluation of patient's working ability concluded that the patient was not
      capable of psychic strains and jobs associated with material accountability.

PMID- 16972414
TI  - [Isolated hydatid cyst of the adrenal gland].
AB  - INTRODUCTION: Hydatid cyst of the adrenal gland is extremely rare even in
      generalized hydatid disease, with less than 20 cases reported in world literature
      including those found in autopsy. CASE OUTLINE: The authors present the second
      case of the adrenal gland hydatid cyst described in Serbian literature, in 52
      year old woman. During the investigation for the epigastric pain by
      ultrasonography and computed tomography, calcified cyst of the sixth segment of
      the liver, 44x39 mm in diameter, was diagnosed. However, during an open surgery,
      it turned out to be the cyst of the right adrenal gland. The cyst as well as the
      entire adrenal gland was removed. The hydatid nature of the cyst was confirmed by
      histological examination. The post-operative recovery was uneventful. The patient
      has remained symptom-free over two years after the surgery. CONCLUSION: To the
      best of our knowledge, this is the second case reported in Serbian and 18th case
      published in world literature.

PMID- 16972415
TI  - [Skin necrosis of penis after chemotherapy regimen in patients with resistant
      nonseminomatous testicular tumor].
AB  - The majority of patients with resistant nonseminomatous testicular tumor can be
      cured with standard chemotherapy based on cisplatin regimen. However, complete
      remission cannot be achieved in 10%-30% of patients, or the disease recurs after
      the first chemotherapy cycle, on what account the salvage chemotherapy is
      administered. The initial BEP chemotherapy was applied in patients with gonadal
      nonseminomatous tumors B2 clinical stage after the left side inguinal
      orchiectomy. Due to manifested resistance, further chemotherapy was given
      according to VIP and one cycle by VEIP regimen. Upon inserting the urinary
      catheter because of total urinary retention, the phlegmonous inflammation and
      subsequently the necrosis of preputial and corpus skin of the penis were
      observed. The necrectomy with autotransplant was performed after demarcation. The
      skin necrosis of penis is very rare post chemotherapy complication in the stage
      of evident peripheral pancytopenia that may be the result of toxic effects of the
      used cytostatics or development of local infection with resulting necrosis.

PMID- 16972416
TI  - [Neurocysticercosis--pathogenesis and clinical aspects].
AB  - Neurocysticercosis is an infestation of the central nervous system with the
      larval cysts of the pork tapeworm (Taenia solium), when a man is paratenic host
      of the parasite. The infection results from ingestion of food or water
      contaminated with human feces containing the parasitic eggs. Much rarely, the
      infection is caused by autoinoculation, when the mature parasites are present in
      the small intestines, and reversed peristalsis gives rise to regurgitation of
      gravid proglottides (internal auto-infestation), or by ingestion of the eggs from
      one's own feces (external auto-infestation). The embryos (oncospheres) develop
      from the eggs, penetrating the small intestine mucosa and entering the
      circulation and subsequently different tissues and organs where cysticerci, small
      tissue larvae, are developed. Cysticerci have specific affinity for the central
      nervous system, eyes and striated muscles what is accounted for high
      concentration of glucose or glycogen in these organs. Neurocysticercosis is the
      most frequent parasitic disease of the central nervous system and the most common
      cause of convulsions and hydrocephalus in the adults in endemic regions, where
      the seroprevalence of disease is about 4% of population. Neurocysticercosis is
      classified into six clinical syndromes: asymptomatic, parenchymal, subarachnoid,
      intraventricular, spinal and ocular forms. Albendazole (benzimidazole) of 15
      mg/kg/BW during 8-28 days or praziquantel (pyrazolone quinoline) of 50-60
      mg/kg/BW during 15 days (or 100 mg/kg/BW only one day) are applied for treatment
      of neurocysticercosis.

PMID- 16972417
TI  - [Graf's method in the ultrasound diagnostics of developmental dislocation of the
      hip].
AB  - The authors present the possibilities of ultrasound diagnostics of developmental
      dislocation of the hip. Special attention has been paid to Graf's method,
      originally developed in Austria and Germany that has been introduced in many
      countries all over Europe, including our country. The method in details, normal
      and pathological anatomy of the infant's hip, all the sonographic types and
      subtypes with therapeutic implications were described.

PMID- 16972418
TI  - Fatigue, depression & cravings.

PMID- 16972419
TI  - Establishing a local NP group.

PMID- 16972420
TI  - RBRVS and your salary package.

PMID- 16972421
TI  - Tick removal techniques.

PMID- 16972422
TI  - Patient information. The importance of homocysteine.

PMID- 16972423
TI  - Soy isoflavones for postmenopausal symptoms. An examination of evidence.

PMID- 16972424
TI  - Patient information. Eggs: a delicious way to protect your sight.

PMID- 16972425
TI  - Promote wellness with aromatherapy.

PMID- 16972426
TI  - An introduction to amino acids.

PMID- 16972427
TI  - From fish to flaxseed. Reducing cardiac risk with omega-3 fatty acids.

PMID- 16972428
TI  - Bladder dysfunction in women. Products and devices play important role.

PMID- 16972429
TI  - Obesity in older adults. A major contributor to chronicity.

PMID- 16972430
TI  - Foot ulcerations and osteomyelitis in diabetes.

PMID- 16972431
TI  - Obstructive apnea. No need to lose sleep over it.

PMID- 16972432
TI  - Embrace the unexpected.

PMID- 16972435
TI  - Who you gonna call? BON not always best choice.

PMID- 16972436
TI  - Prostate cancer: screening and early detection.

PMID- 16972437
TI  - Staying certified.

PMID- 16972438
TI  - Persistent dyspnea with HF.

PMID- 16972439
TI  - Medicare Part D: primer.

PMID- 16972440
TI  - Patient information. Seasonal affective disorder.

PMID- 16972441
TI  - When stroke strikes. Minimizing impact and maximizing recovery.

PMID- 16972442
TI  - Power against prostate cancer. Intensity-modulated radiation therapy and
      interstitial brachytherapy.

PMID- 16972443
TI  - Innovative interventions. What's new and what's ahead for osteoporosis.

PMID- 16972444
TI  - Polypharmacy in older adults. Front-line strategies.

PMID- 16972445
TI  - Tympanocentesis in pediatric primary care. Greater use could meet clinical needs.

PMID- 16972446
TI  - A deceptive presentation: Addison's disease.

PMID- 16972447
TI  - Establishing an ICD support group. A framework.

PMID- 16972448
TI  - When the unspeakable happens. Helping families mourn a stillborn loss.

PMID- 16972449
TI  - Remembering Sophie.

PMID- 16972450
TI  - Making your voice heard. Lessons learned on Capitol Hill.

PMID- 16972451
TI  - Friends in the right places.

PMID- 16972452
TI  - Smoking cessation in men.

PMID- 16972453
TI  - Negotiating your first employment agreement.

PMID- 16972454
TI  - Test questions about pregnancy.

PMID- 16972455
TI  - Patient information. Caring for your teeth and gums.

PMID- 16972456
TI  - Anal pap screening in men with HIV.

PMID- 16972457
TI  - Androgen and the aging man.

PMID- 16972458
TI  - Premature ejaculation.

PMID- 16972459
TI  - Genitourinary tract infections.

PMID- 16972460
TI  - In continence in men.

PMID- 16972461
TI  - Tailor made.

PMID- 16972462
TI  - Curtailing the spread of disease.

PMID- 16972463
TI  - Getting to the big game.

PMID- 16972464
TI  - Pharyngitis in adults.

PMID- 16972465
TI  - Novel ways to attract patients.

PMID- 16972466
TI  - Lung cancer in women.

PMID- 16972467
TI  - Thoracostomy tube removal.

PMID- 16972468
TI  - Patient information. Tips for lowering your cholesterol.

PMID- 16972469
TI  - Cervical cancer screening today. The role of HPV DNA testing.

PMID- 16972470
TI  - The electronic office. How automation can make you happier, richer and more
      effective.

PMID- 16972471
TI  - Qualifying your practice. The road to FQHC status.

PMID- 16972472
TI  - Thinking outside the box. How nontraditional practice is paying off for some NP
      entrepreneurs.

PMID- 16972473
TI  - Medical aesthetics. A growing practice specialty for NPs.

PMID- 16972474
TI  - Too young to grow. Diagnosis and treatment of precocious puberty.

PMID- 16972475
TI  - Celiac disease. A condition with multiple faces.

PMID- 16972476
TI  - Read that meter! Getting the most out of blood glucose monitoring.

PMID- 16972477
TI  - Once-daily intranasal corticosteroids for allergic rhinitis. Examining Treatment
      issues.

PMID- 16972478
TI  - Giving back.

PMID- 16972479
TI  - Why weight?

PMID- 16972480
TI  - What's in a name?

PMID- 16972481
TI  - An action plan for coding.

PMID- 16972482
TI  - Unna boot application.

PMID- 16972483
TI  - Behavior change in overweight patients. Motivational interviewing as a primary
      care intervention.

PMID- 16972484
TI  - Billing for obesity treatment.

PMID- 16972485
TI  - Pharmacologic treatment for obesity. Options for today...and tomorrow.

PMID- 16972486
TI  - Meal replacements for weight management. Carefully chosen bars and shakes can be
      valuable.

PMID- 16972487
TI  - Women and weight. Management strategies throughout the life cycle.

PMID- 16972488
TI  - Behind the extra wheeze & cough. GERD in the patient with asthma.

PMID- 16972489
TI  - Allergic rhinitis in children. The case for second-generation antihistamines.

PMID- 16972490
TI  - Are you ready to be a preceptor?

PMID- 16972491
TI  - Teaching by example.

PMID- 16972492
TI  - [Occupational health services already in school. But school health services today
      are probably not authorized to complete the task].

PMID- 16972493
TI  - [Diagnosis of acute pulmonary embolism. Simplified strategy based on clinical
      probability, D-dimer and computer tomography].

PMID- 16972494
TI  - [Lung carcinoids--not so benign as earlier believed].

PMID- 16972495
TI  - [Similarities and differences in Scandinavian child health services. Sweden has
      the best conditions for good physician-nurse cooperation].

PMID- 16972496
TI  - [Life-saving mechanical compression during percutaneous coronary intervention].

PMID- 16972497
TI  - [Age-related cataract].

PMID- 16972498
TI  - [General practitioner and knowledge].

PMID- 16972499
TI  - [Can vaccination against cervix cancer be an ethical and psychological problem?].

PMID- 16972500
TI  - Stepping up to tobacco control: harnessing the momentum.

PMID- 16972501
TI  - The fourth pillar of the Framework Convention on Tobacco Control: harm reduction
      and the international human right to health.

PMID- 16972502
TI  - The tobacco industry's response to the COMMIT Trial: an analysis of legacy
      tobacco documents.
AB  - We analyzed internal tobacco industry documents that describe the industry's
      response to the Community Intervention Trial for Smoking Cessation (COMMIT), a
      multi-center community-based tobacco intervention project funded by the National
      Cancer Institute from 1988 to 1992. Our analysis of documents from the Legacy
      Tobacco Documents Library (www.legacy.library.ucsf.edu) suggests that the tobacco
      industry reacted to COMMIT by (1) closely monitoring trial activities, (2)
      confronting COMMIT in communities where it was most active, (3) distorting COMMIT
      findings on underage smoking data reported in the media, and (4) using COMMIT
      activities as practice to strengthen their attack against the subsequent ASSIST
      trial, falsely accusing both studies of illegal political lobbying with
      taxpayers' money. The tobacco industry closely monitored COMMIT activities and
      organized local responses to findings and activities perceived as threatening to
      the industry's public image or interests. Although we could not document a
      concerted attack by the tobacco industry that impacted the results of the COMMIT
      trial, data suggest that the industry used COMMIT as a learning opportunity to
      mount a well orchestrated and potentially damaging response to the larger
      American Stop Smoking Intervention Study for Cancer Prevention Trial.

PMID- 16972503
TI  - The development, achievements, and aspirations of a university network dedicated
      to tobacco control research and education.
AB  - The establishment of a university-based network of colleagues with a shared goal
      of increasing tobacco research and educational opportunities can enrich the
      learning environment and ultimately contribute to reducing the toll of smoking.
      Such a network was established at the University of Michigan, and similar
      approaches can be adopted at other universities, considering a range of funding
      levels. This article discusses the mission, structure, accomplishments, and
      future goals of the network, along with lessons learned and recommendations for
      successful initialization. Specific examples of network activities are provided,
      along with references to web sites and lectures. This case study will be useful
      to any university leader seeking to establish a network of tobacco and nicotine
      researchers on campus.

PMID- 16972504
TI  - The UCLA tobacco control program.
AB  - Tobacco use, the most preventable cause of death in our society and a growing
      international epidemic, should be well understood by all students preparing to
      enter the field of public health. Despite its importance, however, tobacco does
      not always enjoy the prominence it deserves in public health education. We report
      here on efforts to expand the focus on tobacco in the University of California
      Los Angeles School of Public Health through a program supported by the
      Association of Schools of Public Health/American Legacy Foundation's Scholarship,
      Training, and Education Program for Tobacco Use Prevention funding mechanism. We
      describe steps to increase tobacco content in required and elective courses;
      offer elective courses on tobacco; implement a pre-doctoral scholarship program
      featuring coursework, fieldwork, and exposure to tobacco issues at national
      meetings; and establish a tobacco-focused workshop series. We outline program
      successes, structural barriers to achieving some programmatic goals, and the
      program's early termination.

PMID- 16972505
TI  - Reaching and educating the global tobacco control community: innovative
      approaches to tobacco control training.
AB  - To slow and end the growing global burden of tobacco-related death and disease,
      schools of public health need to provide tobacco control education and training
      for public health professionals generally, and for the next generation of tobacco
      control professionals in low- and middle-income countries specifically. As the
      tobacco epidemic continues to grow, there is an increasing need for training to
      develop the research and intervention skills required to stem the epidemic and
      reduce the inevitable burden of disease and death. A wide range of educational
      approaches has been developed to increase tobacco control educational capacity in
      high-, middle-, and low-income countries, including traditional on-site classes,
      on-line courses, open source courseware, summer school programs, and training
      workshops. This article provides a perspective on the education and training
      needs of tobacco control researchers around the world and reviews the strengths
      and weaknesses of education and training approaches currently being used in
      tobacco control by schools of public health. In each case, we draw on the
      experience of the Johns Hopkins Bloomberg School of Public Health in educating
      national and international audiences in tobacco control.

PMID- 16972506
TI  - Building an academic tobacco control program while forging links with practice:
      the University of Washington Tobacco Studies Program.
AB  - Despite the tremendous impact that tobacco use and tobacco smoke exposure have on
      morbidity, mortality, and health disparities, few schools of public health in the
      U.S. offer courses of study on tobacco control or make it a priority in their
      curricula. An academic concentration in tobacco studies and a master's-level
      scholarship program were developed at the University of Washington School of
      Public Health and Community Medicine to support and encourage students to pursue
      tobacco-related coursework, seminars, internships, and thesis work. This article
      discusses the goals, strategies, and accomplishments of the programs, emphasizing
      a collaborative approach between the university and state and local health
      departments, nongovernmental agencies, and research organizations as instrumental
      to the program's success and ultimate continuation.

PMID- 16972507
TI  - Reducing the gap between the economic costs of tobacco and funds for tobacco
      training in schools of public health.
AB  - Tobacco use costs approximately dollar 167 billion annually in the U.S., but few
      tobacco education opportunities are available in schools of public health.
      Reasons for the discrepancy between the costs of tobacco use and the creation of
      tobacco training opportunities have not been well explored. Based on the
      Behavioral Ecological Model, we present 10 recommendations for increasing tobacco
      training in schools of public health. Six recommendations focus on policy changes
      within the educational, legislative, and health care systems that influence funds
      for tobacco training, and four recommendations focus on strategies to mobilize
      key social groups that can advocate for change in tobacco control education and
      related policies. In addition, we present a model tobacco control curriculum to
      equip public health students with the skills needed to advocate for these
      recommended policy changes. Through concurrent changes in the ecological systems
      affecting tobacco control training, and through the collaborative action of
      legislators, the public, the media, and health professionals, tobacco control
      training can be moved to a higher priority in educational settings.

PMID- 16972508
TI  - Using technical assistance to strengthen tobacco control capacity: evaluation
      findings from the Tobacco Technical Assistance Consortium.
AB  - Immediately following the Master Settlement Agreement of 1998 and the
      corresponding growth of new and existing tobacco control programs, it became
      clear that tobacco prevention and control organizations required technical
      assistance to help them carry out their missions. The Tobacco Technical
      Assistance Consortium (TTAC) was established at the Rollins School of Public
      Health in 2001 to provide tailored technical assistance services to meet the
      needs of the expanded workforce and to build tobacco control capacity. To
      understand whether and how TTAC's technical assistance enhanced capacity, TTAC
      conducted an evaluation of its services through semi-structured telephone
      interviews with the primary contacts and one to two additional informants for
      each of 48 technical assistance services provided over an 18-month period. The
      majority of respondents reported they had increased knowledge and skills in
      tobacco control, strengthened leadership skills, developed or strengthened
      partnerships with other tobacco control organizations, and changed the way they
      practice tobacco control following the assistance. More modest improvements were
      noted in the areas of increased organizational support and policy change at the
      local or state level.

PMID- 16972509
TI  - A case-based clinician training program for treating tobacco use in college
      students.
AB  - Tobacco use rates are high among college students, and while many of them try to
      quit every year, only a small percentage are successful at maintaining
      abstinence. Most colleges have campus health centers that offer treatment for
      tobacco cessation, but few students access these resources. Little is known about
      how to motivate young adult college students to seek treatment or assist them in
      their attempts to quit smoking. In the context of a comprehensive, group
      randomized intervention study to decrease smoking among college students, a case
      based tobacco cessation training program for campus health center providers and
      staff was developed and conducted at 14 intervention colleges during the 2003
      2004 academic year. Six case studies were created for this training, using
      responses from 39 student elicitation interviews conducted at 12 colleges in
      Spring 2002. Common themes relating to smoking, quitting, and relapse experiences
      reported by students in the elicitation interviews were woven into the cases and
      integrated into the training program.

PMID- 16972510
TI  - Are state patterns of smoking different for different racial/ethnic groups? an
      application of multilevel analysis.
AB  - OBJECTIVES: Tobacco use research has often assumed "average" effects across
      place, race, and socioeconomic position. We explored and mapped the variation in
      smoking prevalence for racial/ethnic groups by gender and state after adjusting
      for demographic factors. METHODS: We executed a cross-sectional, weighted, two
      level multilevel multiple regression analysis (individuals in states), with
      current smoking as the outcome, using the 1995-1996 Current Population Survey
      Tobacco Use Supplement, for non-Hispanic (NH) whites, NH blacks, and Hispanics.
      We also calculated adjusted smoking prevalence, 95% confidence intervals,
      Spearman correlations, and state residual-based maps to examine state patterns.
      RESULTS: We found different smoking patterns for each racial group. Black women's
      smoking rates were markedly lower than the national subgroup rate in six
      clustered states in the deep South. Smoking rates for whites were higher than the
      subgroup national rate in several Great Lakes states, Texas, Nevada, and North
      Carolina. For white women, several rural Midwest states displayed lower-than
      expected smoking rates (Idaho, Utah, South Dakota, and Nebraska). We documented
      positive correlations for smoking prevalence between men and women within each
      racial group, but not between racial groups, indicating a race-specific pattern
      of smoking. We found that state tobacco variables (taxation and agriculture) did
      not account for remaining state smoking variance after inclusion of demographic
      variables. CONCLUSION: Multilevel modeling may enhance surveillance of tobacco
      use patterns. Focusing on race-specific state smoking patterns may illuminate why
      racial/ethnic minority groups exhibit lower smoking prevalence compared to their
      white counterparts, by examining context of smoking that may be race-specific.

PMID- 16972511
TI  - The meanings and context of smoking among Mexican university students.
AB  - OBJECTIVES: We sought to describe the dominant social contexts and meanings of
      smoking among Mexican university students. METHODS: Structured observations were
      made and individual in-depth interviews were conducted with 43 university
      students who were at five levels of involvement with smoking (i.e., never smoker;
      ex-smoker; experimenter; regular smoker; frequent smoker). Content analysis of
      interview transcripts was used to distill the primary settings and themes that
      students associated with smoking. RESULTS: Outside their homes and away from the
      purview of their parents, the environments that students frequented were
      permissive of smoking, supporting their perceptions of smoking behavior,
      cigarettes, and the tobacco industry as normal and socially acceptable. Cigarette
      smoking was a highly social practice, with students practicing simultaneous
      smoking and cigarette sharing to underscore bonds with others. Moreover, the
      leisure times and places in which students smoked appeared to bolster their
      perceptions of cigarettes as offering them pleasurable relaxation and escape from
      boredom and conflictual social relations. All students believed that smoking was
      addictive and that second-hand smoke was dangerous to non-smokers. The short-term
      negative outcomes of smoking appeared more salient to students than either the
      longer-term health outcomes of smoking or the practices of the tobacco industry.
      CONCLUSIONS: The meanings and context of smoking were comparable to those found
      among youth in other parts of the world. Successful tobacco prevention messages
      and policies to prevent smoking in other youth populations may also succeed among
      Mexican youth.

PMID- 16972513
TI  - Smokers' beliefs and attitudes about purchasing cigarettes on the Internet.
AB  - OBJECTIVES: Our objectives were to explore qualitatively how smokers find out
      about Internet cigarette sales and what factors motivate them to purchase
      cigarettes on-line, and to quantitatively describe the Internet cigarette
      purchasing behaviors and attitudes of Internet cigarette buyers. METHODS:
      Qualitative in-depth telephone interviews were conducted with 21 adult smokers
      who had purchased or contemplated purchasing cigarettes online. Findings from the
      qualitative study were used to develop a survey module on Internet cigarette
      purchasing behavior that was administered to 187 New Jersey adult smokers.
      RESULTS: Smokers who purchased cigarettes on-line were primarily motivated by
      lower prices, which occur because Internet vendors generally sell cigarettes
      without paying excise taxes for the destination state. Most Internet cigarette
      buyers first learned about on-line cigarette sales from interpersonal sources who
      had purchased on-line. New Jersey adult smokers who purchased cheaper cigarettes
      from the Internet and other lower-taxed sources significantly increased their
      consumption over time, compared to smokers who reported paying full-price at
      traditional bricks-and-mortar retail stores. CONCLUSIONS: Policies that have the
      effect of equalizing Internet cigarette prices with those at retail stores will
      likely deter smokers from purchasing cigarettes on-line. Internet cigarette
      vendors should be required to comply with the same provisions that apply to
      bricks-and-mortar retail vendors and charge appropriate state and local cigarette
      excise taxes. In the absence of such policies, the sales of cheaper, tax-free
      cigarettes on-line will undermine the public health benefit of raising cigarette
      prices.

PMID- 16972512
TI  - Preferred smoking policies at 30 Pacific Northwest colleges.
AB  - OBJECTIVE: Research shows that restrictive smoking policies on college campuses
      could discourage smoking onset or help facilitate cessation efforts among
      students. However, many colleges and universities are reluctant to establish
      restrictive smoking policies for fear of student objections. Our study examined
      preferred smoking policies among college students in the Pacific Northwest.
      METHODS: We conducted a baseline cross-sectional descriptive study of a grouped
      randomized controlled trial at 30 four-year colleges and universities in Idaho,
      Oregon, and Washington. RESULTS: Of the 14,237 students who responded to the
      survey, 17.3% were smokers. All respondents were knowledgeable about indoor
      smoking policies; however, there was incongruence regarding outside policies.
      Some 88% of never smokers wanted a completely smoke-free indoor policy, while a
      substantial percentage (58%) of smokers concurred (odds ratio [OR]=0.19,
      p<0.001). Fewer respondents were supportive of outdoor policies (43.3% for never
      smokers and 6.9% for smokers). Respondents agreed that the desire to breathe
      clean air should have priority over the desire to smoke; however, smokers agreed
      to a lesser extent (97.5% for never smokers and 81.5% for smokers [OR=0.012,
      p<0.001]). CONCLUSION: Both non-smokers and smokers have high approval rates for
      restrictive smoking policies on campus. Administrators can use this information
      to help enact restrictive campus smoking policies.

PMID- 16972516
TI  - The National Uniformity for Food Act: implications for public health policy and
      practice.

PMID- 16972514
TI  - The relationship of cigars, marijuana, and blunts to adolescent bidi use.
AB  - OBJECTIVE: Previous research suggests that bidi, cigar, and marijuana use may be
      interrelated, but to date, this hypothesis has not been empirically tested.
      METHODS: We explored the relationships among use of these products using data
      from 17,429 youths who completed the 2001 National Household Survey on Drug
      Abuse. Variables of interest included demographics, tobacco use (i.e.,
      cigarettes, cigars), marijuana use, and blunting (i.e., cigars filled with
      marijuana). Adjusted odds ratios (AOR) for past-month bidi use were generated for
      each variable; regression models were also generated separately by
      race/ethnicity. RESULTS: Overall, 1.1% of the youths surveyed reported past month
      bidi use; higher prevalence was noted for those who were past-month users of
      cigarettes (4.6%), cigars (7.0%), marijuana (5.8%), and blunts (7.3%). Logistic
      regression yielded significant odds ratios for all tobacco products, marijuana,
      and blunts, with the greatest odds associated with past-month cigarette use.
      Interestingly, the pattern varied notably by race. Among white youth, the
      greatest odds for past-month bidi use were associated with cigarette use
      (AOR=3.9), while among black youth the greatest odds were associated with
      blunting (AOR=9.5). CONCLUSION: The findings demonstrate that the use of cigars
      and blunts is highly associated with bidi use among youths and these patterns
      differ by race/ ethnicity. Tobacco control efforts that target youths must
      address other tobacco products and marijuana and should be tailored appropriately
      and effectively, with consideration of racial, ethnic, and cultural variations.

PMID- 16972515
TI  - Saving the asbestos industry, 1960 to 2006.

PMID- 16972517
TI  - Effect of price and smoking characteristics on the decision to smoke smuggled
      cigarettes in Taiwan.

PMID- 16972518
TI  - Recommendations from the ASPH/Legacy Scholarship, Training, and Education Program
      for Tobacco Use Prevention (STEP UP) strategy planning meeting Chicago, May 3,
      2005.
AB  - During this meeting, the participants developed a strategic set of
      recommendations for ASPH to continue to advance the study of tobacco control in
      public health through research and education/training programs. The meeting
      focused on sustaining and further developing tobacco-related research and
      education/ training programs. All four issues were addressed in depth through
      valuable discussion and exchange and reflected in the nine areas of focus.
      Recommendations for advocacy for future funding for SPH in tobacco control
      included developing collaborative relationships with ASPH partners,
      organizations, and institutions with complementary objectives (state departments
      of health, third party payors, etc). Priorities for sustaining and further
      developing research and education/training programs within SPH included
      developing a focus on particular research areas (e.g., special populations,
      economic issues, dissemination and translational issues), building on existing
      knowledge, and attempting to avoid the effects of "siloing" with collaborative
      relationships and methods for addressing the sustenance of programs beyond
      initial funding periods. Methods to maintain vigilance on tobacco control with
      increasing concerns about other risk factors included fostering an increasing
      awareness of tobacco-related issues, projects, and programs as well as developing
      collaborative relationships with organizations and institutions with
      complementary health-risk related objectives. Other recommendations focused on
      enhancing SPH leadership in the tobacco control field by developing standards and
      methodologies and translating research to practice. They included (1) developing
      standards for consistent tobacco control-related education to public health
      students, public health professionals, and other students and professionals; (2)
      developing a standardized method for evaluating tobacco-attributable factors and
      effects; and (3) conducting effectiveness trials of treatments known to be
      efficacious. Effectively addressing these perennial issues will enable SPH to
      enhance its leadership position and contribute greatly to research and
      education/training in tobacco control. All of these issues were factors in
      program planning for the second National STEP UP Academic Tobacco Workshop. For
      instance, reviews of particular research areas might be offered or facilitated as
      well as methods for developing collaborative partnerships and subsequent efforts.
      Steps toward the development of tobacco control education core competencies might
      be developed as well. The second National STEP UP Academic Tobacco Workshop-STEP
      UP to Sustain Tobacco Control and Prevention through Education and Research--was
      held on January 30-31, 2006. The topics of discussion ranged from use of
      secondary data to behavioral economics. More information about the workshop can
      be found at http://www.asph.org/ document.cfm?page=882. Attention to the
      recommendations that resulted from the planning meeting will provide a strategic
      platform from which ASPH and the public health community can continue to address
      the single greatest cause of preventable disease and death in the world.

PMID- 16972519
TI  - Multiple perspectives on collaboration between schools of public health and
      public health agencies.

PMID- 16972520
TI  - [Analysis of the perinatal results of the first five years of the functioning of
      a clinic for pregnant teenagers].
AB  - OBJECTIVE: To evaluate the perinatal outcomes within a pregnant cohort of
      adolescents aged 16 years and younger. PATIENTS AND METHODS: Case review
      prospective study. All pregnant adolescents who attended to the Coordination for
      assistance of the adolescent patient from June 1998 to July 2003 were included.
      INCLUSION CRITERIA: age, irrespective from antenatal care inside or outside of
      the Coordination and delivering inside the institution. Variables analyzed were:
      age, occupation, marital status, gestational age at first antenatal visit, number
      of antenatal visits, medical complications during pregnancy, gestational age on
      delivery, mode of delivery and contraceptive acceptance on discharge. Neonatal
      variables: weight at birth and intensive care admissions. Statistical analysis
      included descriptive measures. RESULTS: We identified 2723 pregnant adolescents,
      from whom only 2,315 met the inclusion criteria. Mean maternal age was 15.3 (SD
      0.87). From the total 58% were single and 83.4% were households while only. Mean
      gestational age on first visit at the coordination was 24.26 (SD 6.79) weeks. The
      average number of antenatal visits was 4.78 (SD 3.99). The most frequent medical
      complications affected the genital and urinary tract, with a 54.2% of cervical
      and vaginal infections, and a 23.8% of urinary tract infections; anemia in 16.7%,
      threatened preterm delivery in 9.2% and pregnancy induced hypertension in 3.8%.
      From the total of cases the 79.1% presented with any morbidity. Mean gestational
      age concluded at 37.58 (SD 3.03), the preterm delivery rate was 15.4%. The most
      frequent way of delivery was vaginal with a 55.8% rate. On the neonatal outcomes,
      the mean birth weight was 2819.07 (SD 613.85). The contraceptive acceptance on
      the discharge was 98%. CONCLUSIONS: The adolescent pregnant has a high risk of
      suffering major complications, such as genital and urinary tract infections,
      anemia and preterm delivery.

PMID- 16972521
TI  - [Modification of the cut-off values in the gestational diabetes-screening test].
AB  - OBJECTIVE: To demonstrate that specificity to diagnose gestational diabetes
      increases when the end point diminishes from 180 to 170 mg/dL. MATERIAL AND
      METHODS: We made a transversal study based on the collection of 200 files
      randomly chosen, and whose diagnose was gestational diabetes identified by
      screening test. We established two end points: 180 and 170 mg/dL. The statistical
      analysis was based on the efficacy values for each one of them. Likelihood ratios
      for both tests were compared with the gold standard of the oral glucose tolerance
      test, 3 h with 100 g of glucose. A hundred patients were chosen for each group
      (the end point of the first and second group was greater than 180 and 170 mg/dL,
      respectively). RESULTS: The screening test results of the first group varied
      between 130 and 180 mg/dL. Fifty tolerance curves of four samples were negative
      and 50 were abnormal; 30 of these had diagnosis of gestational diabetes and 20
      carbohydrate intolerance. In the second group the screening test results varied
      from 130 to 170 mg/dL. Sixty four tolerance curves of four samples were normal
      and 36 were abnormal; 24 of these had diagnosis of gestational diabetes and 12
      carbohydrate intolerance. CONCLUSIONS: Modifying the superior end point of the
      glucose screening test, from 180 to 170 mg/dL, maintains the test sensitivity and
      improves its specificity.

PMID- 16972522
TI  - [Active management of the premature membrane rupture in pregnancies of 34 to 37
      weeks].
AB  - BACKGROUND: Premature rupture of membranes is considered an obstetrical emergency
      since it has been associated with an increment of sepsis and maternal-fetal
      morbidity. For this reason, controversy exists among conservative and active
      management for the obstetrical resolution. OBJECTIVE: To determine if active
      management of premature rupture of membranes in pregnancy of 34 to 37 weeks
      diminishes the cesarean section incidence and the maternal-fetal morbidity.
      PATIENTS AND METHODS: Two groups of patients with pregnancy of 34 to 37 weeks and
      premature rupture of membranes were compared. Group I with active management was
      integrated by 42 cases that initiated inductoconduction at their admission to the
      hospital, and in group II, with 26 cases on the conservative management,
      medication was used to induce fetal pulmonary maturity and spontaneous delivery
      was expected. Descriptive statistics was carried out by means of the statistical
      package SPSS-10. RESULTS: The mean age of the patients was 27.2 +/- 5.8 years.
      Pregnancy resolution within the first 12 hours was 23.8% in group I and 11.5% in
      group II. Cesarean section in group I was made in 28.5% of the cases and in group
      II in 65.3% of them (p < 0.05). The most common indication for cesarean section
      in group I was stationary labor (16.5%) and in group II unfavorable cervical
      conditions (26.9%). Maternal and newborn hospital stay was greater in group II (p
      < 0.01). The most frequent maternal complication in both groups was decidual
      infection, with 4.7 and 15.3%, respectively. General maternal and neonatal
      morbidity was greater in group II. CONCLUSIONS: Conservative management of
      premature rupture of membranes, when pregnancy is equal or greater than 34 weeks,
      does not offer fetal benefits, increases the incidence of cesarean sections, the
      hospital stay and the cost of the medical attention.

PMID- 16972523
TI  - [Infection of the surgical site. Experience of two years in the gynecology and
      obstetric service of Mexican General Hospital].
AB  - OBJECTIVE: To know the incidence and causal agents of the surgical site infection
      at the Gynecology and Obstetrics Service of the Hospital General de Mexico.
      MATERIAL AND METHOD: A retrospective, descriptive and analytical study was
      performed on patients with surgical site infection at the Gynecology and
      Obstetrics Service of the Hospital General de Mexico during January 1st, 2000 to
      December 31st, 2001. RESULTS: A global low rate of surgical site infection was
      observed, with predominance on the third life decade patients and on obstetrics
      events (69.5%). The initial treatment consisting of 600 mg intravenous
      clindamycin every eight hours and 500 mg intravenous amikacin every 12 hours
      showed high efficacy. The mean time of hospital stay was nine days; 97% of the
      discharges were due to improvement, with a minimum rate of mortality.
      CONCLUSIONS: The index of surgical site infections for gynecological and
      obstetric procedures is lower than the accepted percentage, but it is more
      frequent in patients submitted to total abdominal hysterectomy.

PMID- 16972524
TI  - [Perinatal results of the patients assessed by fetal hypomotility].
AB  - OBJECTIVE: To describe the perinatal outcome of those patients that come to
      emergency room because of diminished fetal movements. PATIENTS AND METHOD: This
      is a case series in which we evaluated the patients who were attended at the
      Maternal Fetal Medicine Department from January 2002 to December 2003. All
      patients with prenatal control in the institution whatever the basic pathology
      were enrolled in the study. They were evaluated following the institution
      protocol. All data was obtained from maternal and neonatal files. RESULTS: A
      total of 240 patients with mean age of 27 +/- 7 (SD) years were evaluated in the
      study. Ninety of them (37%) were primiparous, 66 (27%) secundiparous, and 44
      (18%) coursed the third pregnancy. Mean gestational age when they were evaluated
      for diminished fetal movements was 37.1 +/- 2.5 (SD) weeks. After the evaluation,
      195 (81%) patients resulted with a reactive non-stress test, 42 (17%) had a non
      reactive stress test with a positive vibroacoustic stimulation test, no patients
      were found with a non-reactive non-stress test and a negative vibroacoustic
      stimulation test. In two patients (< 1%) the register showed ominous pattern. In
      these two preterm cases pregnancy was interrupted. Mean gestational age at birth
      was 39.1 (+/- 1.7) weeks, and 223 (92.91%) born at term. From the two intervened
      cases, one had intrauterine growth restriction and the other asphyxia with
      intraventricular hemorrhage as a consequence. CONCLUSIONS: Hypomotility is one
      manifestation of the loss of fetal well-being and cannot be ignored because there
      are some cases in which intervention is needed. A great number of patients
      without a real risk of asphyxia and with a good perinatal outcome must be
      evaluated, so we have to look for another mechanism of evaluation for these
      patients. A clinimetric method could be an intermediary step between clinic and
      electronic surveillance.

PMID- 16972525
TI  - [Vulvar syringoma: a report of two cases].
AB  - Syringoma is a benign neoplasm of eccrine origin. Lesions often arise around the
      eyes and on the upper cheeks of middle-aged women. Syringomas involving the
      genitalia are rare, they present as multiple, bilateral, skin-colored papules
      over the labia majora. The lesions should therefore be considered in the
      differential diagnosis of multiple papular lesions of the vulva. We report two
      females of 37 and 62 years of age, both observed in a dermatological service.

PMID- 16972526
TI  - [Vaginal leiomyoma].
AB  - Vaginal leiomyomas are rare benign tumors. This is a case report with menstrual
      and urinary difficulties and vaginal mass with inner urethral meatus and hymen
      displacement. Miccional cystourethrography showed a posterior displaced,
      comprised and elongated urethra. Excretory urography and pelvic sonogram were
      normal. Preurethral enucleation extirpation with no complications was practiced.
      Current literature is reviewed.

PMID- 16972527
TI  - [Acrosomal reaction: five decades after its discovery].

PMID- 16972528
TI  - [Surgery of tumors and infectious complications of the genital apparatus during
      pregnancy. 1951].

PMID- 16972529
TI  - Health Care Reform legislation (HB 4021) demands vigilance and involvement.

PMID- 16972530
TI  - Healthy West Virgina Summit focuses on strategies that promote good health.

PMID- 16972531
TI  - Obstetrical and perinatal care in the Komi Republic of the Russian Federation.

PMID- 16972532
TI  - Laser extraction of infected pacemaker and ICD leads: early experience at
      Charleston Area Medical Center.
AB  - Infection of pacing and cardioverter defibrillator (ICD) implants is associated
      with high morbidity and mortality. To report a single center experience of
      extracted leads, we analyzed 42 (11 ICDs and 31 pacemakers) that had been
      extracted using laser sheath technology at Charleston Area Medical Center between
      November 2000 and September 2003. The indications for extractions were infection
      in 48% of the patients (n = 13) and lead malfunction in 52% (n = 14). In the
      infection group, 6 patients presented with endocarditis and 7 with pocket erosion
      and/or infection. Mean patient age was 69.5 years (range 46-96) and mean duration
      of lead implantation was 68.3 months (range 4-149). Complications with lead
      extraction occurred in 15% (n = 4); 1 patient had bleeding from right subclavian
      vein (RSCV); 1 patient had right ventricle perforation; and 2 patients developed
      cardiac tamponade. One patient with tamponade died despite emergency surgery.
      During a follow up of at least 8 months (range 8-42), 19% (n = 5) and 7% (n = 2)
      deaths occurred in the lead malfunction and infection groups respectively. This
      study shows that extraction is effective in treating pacemaker or ICD infections,
      but with a significant complication rate.

PMID- 16972533
TI  - Physician and patient barriers to adherence with cholesterol guidelines.
AB  - Several national studies have shown poor compliance with National Cholesterol
      Education Program II (NCEP) goals. A study we conducted of patients in the
      General Internal Medicine Clinic at the Marshall University Joan C. Edwards
      School of Medicine in Huntington showed that 46% of them were not at NCEP goals.
      We hypothesized that both patient and physician barriers were responsible for
      these findings so we administered two surveys about barriers to cholesterol
      management to 261 random patients identified with hypercholesterolemia and to all
      50 residents and faculty at the clinic. We identified insufficient knowledge of
      low cholesterol foods as a patient barrier (31.6% of patients), and inadequate
      time to review NCEP guidelines as a physician barrier (45.5% of physicians). We
      conclude that many patients in our practice lack the knowledge of what foods are
      low in cholesterol and that our physicians may not use the NCEP guidelines
      because they are inconvenient to access in our clinic. Future research should
      explore ways to improve patient knowledge of low cholesterol foods and
      accessibility of guidelines for use during patient visits.

PMID- 16972534
TI  - Anterior spinal artery syndrome in a 16-year-old male.
AB  - Spinal cord infarction is a relatively uncommon condition in young children and
      adolescents, however, it should be included in the differential diagnosis of
      acute cord compression. Depending on the vessel involved, the clinical
      presentation may differ. The degree of recovery in spinal cord infarcts varies
      from one individual to another. Recovery of motor function is progressive in most
      of the patients, with the deficit being maximal at the onset. For successful
      outcome, it is imperative that these patients get access to approriate
      rehabilitation very early in the course of the disease. Prevention and early
      treatment of specific complications, especially chronic pain, is of vital
      importance in young patients. This article describes our experiences diagnosing
      and treating a 16-year-old boy with anterior spinal artery syndrome.

PMID- 16972535
TI  - [Controversies in judgment criteria of cardiovascular prevention studies].

PMID- 16972536
TI  - [Drug therapy in the elderly. What should we know?].
AB  - Because of the increasing longevity of the population, a growing number of very
      old people are exposed to medications. Drug therapy in this population is
      difficult because of our lack of knowledge. The number of drugs administered is
      generally high and the prescription is often inappropriate. Changes in body
      composition, malnutrition and renal failure can cause drug accumulation and
      toxicity. However, hepatic metabolism via cytochrome P450 does not seem to be
      markedly influenced by oldness. Iatrogenic pathology is frequent in the elderly
      and may lead to hospitalisation and reduction in quality of life. Specific
      education of the medical care team should be promoted in order to tackle this
      important problem of public health.

PMID- 16972537
TI  - [Usefulness of antidepressants in anxiety disorders].
AB  - This article deals with four anxiety disorders particularly frequent in the
      population as well as in general practice: panic disorder, specific phobias,
      social phobia and generalized anxiety. After a brief description of their
      clinical characteristics and prevalence, it provides the general principles of
      treatment and mainly the specific role of antidepressants. Finally, for each
      disorder, a treatment algorithm based on available guidelines is proposed.
      Schematically, antidepressants and particularly selective serotonin reuptake
      inhibitors exhibit a usefulness assessed as important in panic disorder, moderate
      in generalized anxiety, weak in social phobia and absent in specific phobias.

PMID- 16972538
TI  - [Diabetes mellitus and congestive heart failure: physiopathology and treatment].
AB  - Diabetes mellitus increases by 2.5 to 5 the relative risk of congestive heart
      failure. Besides the classical risk factors of congestive heart failure such as
      obesity, arterial hypertension and coronary artery disease that are frequently
      associated to type 2 diabetes, a diabetic cardiomyopathy plays also a role. This
      specific complication is related to metabolic factors and oxidative stress,
      leading to muscular cell apoptosis and fibrosis. The management of a diabetic
      patient with congestive heart failure has several specificities not only
      concerning the treatment of cardiac insufficiency but most importantly concerning
      antidiabetic therapy. The relationship between glitazones, peripheral oedema and
      risk of congestive heart failure is currently raising much interest and
      controversies.

PMID- 16972539
TI  - [Dronedarone establishes and maintains control of sinus rhythm].

PMID- 16972540
TI  - [Aspirin therapy for cardiovascular prevention in the diabetic patient: what have
      we learned from the evidence?].
AB  - Diabetes mellitus markedly increases the risk of cardiovascular diseases, with an
      especially elevated relative risk among women. Aspirin prescription is mandatory
      in secondary prevention, even if the protection by aspirin appears less
      efficacious in diabetic than in non-diabetic patients. In primary prevention,
      available data are paradoxically rather scarce, but also suggest a less effective
      prevention when diabetes is present. Aspirin remains the first antiplatelet agent
      in the diabetic population in all international guidelines of cardiovascular
      prevention although a higher daily dose may be proposed in this subgroup of
      patients (160-300 mg rather than 75-100 mg).

PMID- 16972541
TI  - [Distinction between good synthesizer and good absorber patients to optimize
      cholesterol-lowering therapy].
AB  - The inhibition of cholesterol synthesis by a statin enhances intestinal
      absorption of both cholesterol and various phytosterols. The atherogenic role of
      phytosterols, well proven in hypersitosterolemia, is now suspected in patients
      with premature coronary artery disease. The cholestanol/cholesterol ratio can be
      used as a marker of intestinal cholesterol absorption. Individuals with elevated
      ratio ("high absorbers") have less favourable cholesterol-lowering response and
      cardiovascular protection with statin therapy as compared to individuals with low
      ratio ("high synthesizers"). They may benefit of an adjunct therapy with
      phytostanols or ezetimibe, both being capable to reduce plasma concentrations of
      cholesterol and of phytosterols.

PMID- 16972542
TI  - [Rimonabant improves cardiometabolic risk profile in obese or overweight
      subjects: overview of RIO studies].
AB  - RIO (Rimonabant In Obesity and related disorders) is a large phase 3 programme
      (>6600 patients) evaluating the efficacy and safety of rimonabant (5 or 20
      mg/day), a CBI receptor antagonist of endocannabinoid system, in obese or
      overweight patients with or without comorbidities (RIO-Europe and RIO-North
      America), with untreated dyslipidaemia (RIO-Lipids) or with type 2 diabetes
      treated with metformin or sulfonylurea (RIO-Diabetes). Compared to placebo,
      rimonabant 20 mg/day consistently increases weight loss, reduces waist
      circumference, increases HDL cholesterol, lowers triglyceride levels, diminishes
      insulin resistance, and reduces the prevalence of metabolic syndrome. Almost half
      of the metabolic effects, including adiponectin increase, occur beyond weight
      loss, suggesting a direct peripheral effect of rimonabant.

PMID- 16972543
TI  - [The role of the pharmacist in patient education].
AB  - Interdisciplinary programs promoting therapeutic education rarely involve the
      pharmacist, though his major contribution in the health care system and his
      multiple competencies are of a big help towards patients treatment adherence. As
      a regular patients confident, specially for those who require a long term
      treatment, the pharmacist deserves a better acknowledgment for his therapeutic
      reinforcement's contribution. A research work has been done in the field of
      therapeutic education to inscribe pharmacist's engagement in this topic.
      Instruments have been worked out to measure and to estimate relevant competencies
      used by pharmacists when answering patients needs. More open minded discussions
      and better rearrangement in the pharmacy in order to respect patients intimacy
      would contribute to enhance his competencies which are largely appreciated by the
      public.

PMID- 16972544
TI  - [Celebrating 25 years of the WHO/UNICEF international code of marketing of breast
      milk substitutes].

PMID- 16972545
TI  - [Pancreatic cancer: Roche versus the European Agency of Drugs].

PMID- 16972547
TI  - [The year 2006 - cloning and doping].

PMID- 16972546
TI  - [Avian influenza pandemic prevention - current research].

PMID- 16972548
TI  - [A plethora of possible vaccines against human avian influenza ].

PMID- 16972549
TI  - [Post revolution therapy].

PMID- 16972550
TI  - Determination of vanadium accumulation in onion root cells (Allium cepa L.) and
      its correlation with toxicity.
AB  - The vanadium is a metal that presents great interest from the toxicological point
      of view, because of the numerous alterations that can take place in different
      biological systems. This work evaluated the capacity of vanadium accumulation and
      its correlation with genotoxic effects in root cells of Allium cepa L. The bulbs
      were cultivated in renovated filtered water each 24 h, at a temperature of 25 +/-
      0.5 degrees C, in darkness and constant aeration. Treatments were carried out
      under the same experimental conditions, using water solutions of vanadium of 25,
      50, 75 and 100 microg/g for 0, 12, 24, 48 and 72 h. A control was carried out
      where metal solution was substituted by distilled water. After the treatment, the
      meristems were fixed with alcohol--acetic acid (3:1) and stained according to the
      technique of Feulgen. The capacity of accumulation was determined by GFAAS. The
      analysis of the results revealed an accumulation of the metal for all times and
      concentrations. No correlation was presented among vanadium accumulation, growth
      and mitotic index; however, positive correlation was given with the induction of
      chromosomic aberrations. In conclusion, vanadium is able to induce cytotoxic
      effect in the exposed roots, but only genotoxic effect was correlated with metal
      accumulation.

PMID- 16972551
TI  - Construction of engineered murine embryonic stem cells with conditional knockout
      of FGFR2 depending on Cre-loxP.
AB  - OBJECTIVE: To investigate the functions of Fibroblast Growth Factor Receptor-2
      (FGFR2) at different stages of cell differentiation. The engineered murine
      embryonic stem (ES) cells with conditional knockout of FGFR2 were developed
      depending on Cre-loxP. METHODS: Cre-loxP system was used in a conditional
      targeting vector. The competent AM-1 bacteria, which expressed Cre-recombinase,
      was used to confirm the Cre-mediated deletion of the floxed exons 7 and 8 of
      FGFR2. The targeting vector was electroporated into the ES cells, and the
      transfected ES cells were screened with G418 and Ganciclovir. Finally, the ES
      clones with correct targeting events were identified by Southern Blot and PCR.
      RESULTS: The targeting vector with conditional knockout of murine FGFR2 was
      successfully constructed and confirmed by PCR and digestion analysis in bacteria.
      86 ES clones were collected by selective culture with G418 and Ganciclovir. Four
      of the 86 ES clones were found containing the targeting gene sequence in genomic
      DNA proved by Southern Blot with a 5'-end flank probe. Two of the four ES clones
      had the correct targeting events that included the insertion of the targeting
      gene sequence in genomic DNA and were checked by Southern Blot with a 3'-end
      flanking probe. Finally, the insertion of loxP (loxP3) between exons 8 and 9 in
      genomic DNA was identified in one of the two ES clones by Southern Blot and PCR.
      CONCLUSION: FGFR2 conditional knockout depending on Cre-loxP can be successfully
      used in ES cells.

PMID- 16972552
TI  - Comparative fine structure of the epididymal spermatozoa from three Korean shrews
      with considerations on their phylogenetic relationships.
AB  - This study examined the fine structures of epididymal spermatozoa on the lesser
      white-toothed shrew (Crocidura suaveolens), the Japanese white-toothed shrew (C.
      dsinezumi) and the big white-toothed shrew (C. lasiura) belonging to the
      subfamily Crocidurinae living in Korea. In the spermatozoa of C. suaveolens, the
      head has a large acrosome, a smooth inner acrosomal membrane and a wavy, finger
      like, electron-dense apical body. The neck has a solid proximal centriole that is
      filled with electron-dense material. These results showed the spermatozoa of C.
      suaveolens possess the characteristics of both Crocidurinae and Soricinae. In C.
      dsinezumi and C. lasiura, the head has a large acrosome, a serrated inner
      acrosomal membrane and a common apical body. The neck has a fistulous proximal
      centriole with slightly dense electron granules. These results showed the typical
      characteristics of Crocidurinae. Although C. suaveolens belongs to the subfamily
      Crocidurinae, the spermatozoan morphology is different from C. dsinezumi and C.
      lasiurai because it has conserved characteristics of the subfamily Soricinae.

PMID- 16972553
TI  - Morphology and histology of P. argentinus (Crustacea, Decapoda, Caridea)
      digestive tract.
AB  - This work describes the morphology and histology of the P. argentinus digestive
      tract. The foregut comprises the mouth, oesophagus, and stomach and is lined by a
      simple cylindrical epithelium overlain by cuticle. There are tegumental glands in
      the oral region and in the first portion of the oesophagus and of the hindgut.
      The cardiac stomach is an oval dorsal sac in the cephalothorax and has no
      calcified structures. The pyloric stomach comprises an upper chamber and a lower
      gland filter. The filter consists of an outer row of elongated setae and an inner
      row of dorsally curved setae forming longitudinal channels 16-18 microm wide. The
      midgut runs from the dorsal chamber of the pyloric stomach to the sixth abdominal
      somite without caeca. The hindgut runs from the sixth abdominal somite to the
      ventral anus. The mid-gut epithelium comprises dominant cylindrical cells and
      small undifferentiated cells in the first portion. The hindgut wall presents
      longitudinal folds, conspicuous muscular bundles, and a folded cuticle. The
      digestive tract of P. argentinus is basically similar to that of most of
      decapods. The absence of calcified structures in the stomach and the width of the
      longitudinal channels in the filter are related to the predominantly
      detritivorous diet.

PMID- 16972554
TI  - Effects of the ascorbic acid supplementation on NADH-diaphorase myenteric neurons
      in the duodenum of diabetic rats.
AB  - We assessed the ascorbic acid (AA) supplementation on the myenteric neurons in
      the duodenum of rats. Fifteen rats with 90 days of age were divided into three
      groups: control (C), diabetics (D) and ascorbic acid treated diabetics (DA).
      After 120 days of daily treatment with AA, the duodenum was submitted to the NADH
      diaphorase (NADH-d) histochemical technique, which allowed us to evaluate the
      neuronal density in an area of 8.96 mm2 for each duodenum, and also to measure
      the cellular profile area of 500 neurons per group. The supplementation promoted
      an increase on AA levels. The neuronal density (p < 0.05) was higher in the group
      DA when compared to group D. There were no significant differences in the
      neuronal areas, when we compared groups C (204 +/- 16.5) and D (146.3 +/- 35.84)
      to groups D and DA (184.5 +/- 5.6) (p > 0.05). The AA-supplementation avoided the
      density reduction of the NADHd myenteric neurons in the duodenum of diabetic
      rats.

PMID- 16972555
TI  - Evaluation of a multiplex PCR method to detect enteroaggregative Escherichia
      coli.
AB  - Enteroaggregative Escherichia coli (EAEC) has been implicated in sporadic
      diarrhea in children and adults and has been identified as the cause of several
      outbreaks worldwide. The HEp-2 test remains the gold standard for identification
      of this pathotype. A 60-65 MDa plasmid encodes the aggregative adherence fimbriae
      (AAF/I and AAF/II), a transcriptional activator (aggR gene), the
      enteroaggregative heat-stable enterotoxin EAST1 (astA gene) and a cytotoxin
      (Pet). The standard assay for EAEC is performed only in research laboratories,
      because it is expensive, labor intensive and time-consuming. The Polymerase Chain
      Reaction (PCR) offers the possibility of rapid diagnosis. In the current study, a
      multiplex PCR assay which checks aggR and astA genes was designed. Eigthy-eight
      E. coli strains, isolated from children with acute diarrhea in Mendoza,
      Argentina, were characterized by the reference method (HEp-2 assay), and by aggR
      astA PCR. A strong correlation between the presence of the specific marker aggR
      and the reference test was found. The astA gene had a similar distribution
      between aggregative and localized strains, indicating that this gene could not be
      considered as a marker of EAEC. We conclude that aggR may be used to identify
      EAEC, using the PCR method as a screening test.

PMID- 16972556
TI  - CAS role in the brain apoptosis of Bufo arenarum induced by cypermethrin.
AB  - CAS might have a key role in the apoptosis induced by toxins, acting as anti
      apoptotic factor, stimulating the cellular proliferation and the cell contact
      stabilization. To start to elucidate their role in the brain apoptosis of Bufo
      arenarum induced by cypermethrin (CY), the expression patterns of CAS and several
      cell adhesion molecules (CAMs) were established. Bufo arenarum tadpoles of the
      control and acute bioassay survival at different doses (39, 156, 625 and 2,500
      microg CY/L) and times (24, 48, 72 and 96 h) of CY treatment were fixed in
      Carnoy, embedded in paraffin and sectioned. CAS and CAMs expression was
      determined by immunofluorescence and immunohistochemistry, respectively. When the
      bioassay starts, CAS increases suggesting a proliferative or regenerative effect,
      but decreases when the doses and/or the biocide exposure time increases,
      suggesting compromise of the cellular cycle control and trigger of an apoptotic
      wave. However, these neurotoxic mechanisms should not involve degradation of N
      cadherin and alpha-catenin, in contrast of beta-catenin and axonal N-CAM180, at
      least in the initial apoptotic phase. Additionally, an adhesion compensatory
      mechanism by N-CAM180 is observed in the neuron cell body. These results suggest
      a dual role of CAS in the cellular cycle control during the CY-induced apoptosis:
      induction of cell proliferation and stabilization of the cell-cell junctions by
      modulating CAMs expression.

PMID- 16972557
TI  - Salicylic acid permeation: a comparative study with different vehicles and
      membranes.
AB  - Considering the skin's function, different dermal pharmaceutical forms can be
      developed according to the type of therapeutic activity, active principle and
      excipients involved in the formulation, such as "transdermal preparations". In
      the present study, the permeation parameters of the non-steroidal anti
      inflammatory drug, salicylic acid (SA) through synthetic membrane, polyvinyliden
      difluoride, and a biological membrane, egg shell membrane, with different
      vehicles, propylene glycol, isopropyl alcohol and carbopol gel, were determined.
      The reported physicochemical parameters of SA from CG were significantly higher
      than those obtained using PG and IP. This is attributed to the lipophilic nature
      of the vehicle that facilitates the release and penetration of the active
      principle, thus acting sinergically. The permeation profiles of SA allow us to
      state that permeation kinetics is of first order, so that the flux values
      obtained are in direct proportion to the specific rates of drug release.

PMID- 16972558
TI  - Conchological variation in Pomacea canaliculata and other South American
      Ampullariidae (Caenogastropoda, Architaenioglossa).

PMID- 16972559
TI  - Fossil record of Pomacea (Caenogastropoda: Ampullariidae) in Argentina and its
      paleoenvironmental implications.

PMID- 16972560
TI  - An integrative view to structure, function, ontogeny and phylogenetical
      significance of the male genital system in Pomacea canaliculata (Caenogastropoda,
      Ampullariidae).

PMID- 16972561
TI  - Biochemical composition, tissue origin and functional properties of egg
      perivitellins from Pomacea canaliculata.

PMID- 16972562
TI  - Facultative and obligate symbiotic associations of Pomacea canaliculata
      (Caenogastropoda, Ampullariidae).

PMID- 16972563
TI  - The heart of the matter.

PMID- 16972564
TI  - Balancing act.

PMID- 16972565
TI  - Peace, love and Florence Nightingale.
AB  - Legendary Woodstock music festival star Country Joe McDonald has a fascination
      with Florence Nightingale, dating from his work with Vietnam war veterans.
      Although her theories have diminished in popularity, he believes her life has
      lessons for modern nurses.

PMID- 16972566
TI  - Emotionally smart.
AB  - In the fifth article in our Heart of Nursing series we examine how caring for
      patients demonstrates that nurses value and respect them. To achieve optimum
      care, nurses need emotional intelligence.

PMID- 16972567
TI  - Care distinction.

PMID- 16972568
TI  - Zero tolerance on torture.

PMID- 16972569
TI  - Dangerous liaisons.

PMID- 16972570
TI  - Evaluating a nurse-led DXA scanning service.
AB  - AIM: To examine the feasibility of using a peripheral dual energy X-ray
      absorptiometry (DXA) scanning service in a nurse-led clinic and whether or not it
      would influence treatment and clinician satisfaction with the service. METHOD: A
      nurse-led clinic, using peripheral DXA scans to identify patients at risk of
      osteoporosis, was established in the rheumatology department of the hospital.
      Patients were referred from several sources. A questionnaire was sent to
      referring health professionals with each scan result. Returned questionnaires
      were statistically analysed. Of the sample size of 2000, 1024 questionnaires were
      returned, giving a response rate of 51 per cent. RESULTS: The results confirmed
      the hypothesis that a nurse-led peripheral DXA scanning service is feasible and
      beneficial to referring clinicians. Eighty nine per cent (n=912) of respondents
      stated that the scan results influenced treatment of patients. CONCLUSION:
      Further investigation of the extent that the DXA scanning service may have
      reduced unnecessary treatment is required.

PMID- 16972571
TI  - A pain assessment tool for patients with limited communication ability.
AB  - This article outlines the development and implementation of a multi-dimensional
      pain assessment tool for use in acute hospitals. The tool can assist nurses in
      caring for various patient groups, including patients with limited communication.

PMID- 16972572
TI  - Addressing nursing shortages in sub-Saharan Africa.
AB  - The desperate situation of the health workforce in sub-Saharan Africa (SSA)
      cannot be overstated. This has been a significant and confounding factor in the
      decline in life expectancy in a number of SSA countries. This article identifies
      the reasons for the global shortage of nurses and recommends actions to address
      the crisis in Africa.

PMID- 16972573
TI  - Using mentalisation to treat patients with borderline personality disorder.
AB  - This article provides an overview of personality disorders, before focusing on
      borderline personality disorder. The role of mentalisation in the development of
      borderline personality disorder is explored. It is suggested that mentalisation
      based treatment can greatly improve outcomes for patients.

PMID- 16972574
TI  - Visual impairment in children.

PMID- 16972575
TI  - Jill of all trades.

PMID- 16972576
TI  - All things being equal.

PMID- 16972577
TI  - Positive spin.

PMID- 16972578
TI  - Overcrowding, understaffing and infection in hospitals.

PMID- 16972579
TI  - Dietary iodine intake in pregnancy.

PMID- 16972580
TI  - National survey of diabetes care in general practice.
AB  - This survey was mounted to assess the extent and organisation of diabetes care in
      general practice in Ireland. It was a postal questionnaire surveying 25% of
      general practitioners, The response being 396 (70%). 355 (92%) report providing
      most care to a mean 65% of their type 2 patients, and 243 (64%) provide most care
      to 38% of their type 1 patients. The extent of structured care is less frequent
      with 43% maintaining a diabetes register, and 51% using a recall system. Access
      to multidisciplinary diabetes expertise in the community is low, particularly for
      dietetics (50%) and diabetes specialist nursing (7%). Rural doctors are
      significantly more likely to report providing care to patients with type 1 and 2
      diabetes. Irish general practitioners report providing a substantial amount of
      care, particularly for patients with type 2 diabetes, but this is largely
      unstructured. Significant investment is needed to ensure uniformly structured
      care in this setting.

PMID- 16972581
TI  - Modes of death in neonatal intensive care units.
AB  - With the ever-increasing availability of aggressive medical treatment and
      technical support, neonatologists are offered an increasing ability to prolong
      life. While "end-of-life" decisions within NICUs have been studied
      internationally, there is limited data available for Ireland. Through the
      auspices of the Irish Faculty of Paediatrics 2002 Neonatal Mortality
      Ouestionnaire, decisions made around the time of death in Irish Neonatal
      Intensive Care Units were examined. The overall response rate to the
      questionnaire was 96% (n=25). One hundred and eighty seven deaths were reported
      for 2002. Information pertaining to the mode of death was available in 53% of
      cases. Seventy seven percent of those paediatricians who answered this question,
      reported either withdrawing or withholding treatment in babies thought to have a
      hopeless outcome, with the greatest proportion of these deaths occurring in
      premature infants (n=30) and babies with congenital defects (n=40).

PMID- 16972582
TI  - Is vaginal breech delivery outdated for all singletons and twins? The current
      kaleidoscope of obstetric thinking.
AB  - The best practice for the delivery of a term breech in singleton and twin
      pregnancies is still controversial. We sought the opinions of obstetricians
      working in Ireland. A questionnaire was used to address the management of the
      obstetrician's "own hypothetical pregnancy" in three different scenarios. We also
      inquired about factors which might influence the decision on mode of delivery.
      The response rate was 104/174 (60%). In the scenario of a singleton fetus
      presenting by the breech in a nulliparous woman, 15/84 (18%) of obstetricians
      would chose a spontaneous vaginal delivery compared to 40/80 (50%) for a
      multiparous woman (p < 0.01). In the scenario of a second twin in breech
      presentation (nulliparous and multiparous), 75/93 (81%) would choose a
      spontaneous vaginal delivery. When asked about a singleton cephalic presentation,
      85/91 (93%) would choose a spontaneous vaginal delivery. These decisions were
      influenced by concerns about perinatal morbidity [91/100 (91%)], published
      evidence [73/98 (75%)], the delivery doctor's inexperience [56/94 (60%)], but not
      by gender. Our study indicates that obstetricians in Ireland consider that there
      is a role for vaginal breech delivery in selected scenarios.

PMID- 16972583
TI  - End of life in ICU--care of the dying or 'pulling the plug'?
AB  - This study, a modified subsection of the European ETHICUS study on End-of-Life
      (EOL) Decision Making in the Intensive Care Unit (ICU), examines the pattern of
      limiting futile life-sustaining therapies in an Irish ICU including the practice
      of withdrawing mechanical ventilation in anticipation of death. 1146 patients
      were admitted to the Mater Hospital, Dublin ICU from 1/9/1999 to 30/6/2000 and
      all 126 patients who died in ICU were included. EOL categories were prospectively
      defined (by Ethicus methodology) as cardiopulmonary resuscitation (CPR); brain
      death; withholding (WH); withdrawing (WD) life sustaining therapy and active
      shortening of the dying process (SDP). Complete data were obtained for 122 of the
      126 patients who died during this period. 45 patients (36%) had therapy withheld,
      40 (33%) had therapy withdrawn, 26 (21%) had unsuccessful CPR and 11 (10%) were
      Brain Dead. SDP was not performed. In total, 85 patients had a limitation of life
      sustaining therapy. CPR was the main therapy withheld (96% of WH/WD patients).
      Inotropic infusions were limited (WH or WD) in 40/85 (47%) of patients. Fluids,
      feeding and oxygen were rarely withdrawn (2.4%, 6%, 4.8% respectively). Twenty
      two patients had two or more EOL decisions. Tracheal extubation or withdrawal of
      ventilation was less frequent (16.4%) but more common if a second EOL decision
      was made. No patient had sedation withdrawn or decreased. Eight patients of 85
      (9%) had sedation increased. The study demonstrates that EOL decision making is
      common (69% of deaths and 7.4% of ICU admissions) in Ireland and demonstrates
      that the pattern of treatment limitation relates primarily to cardiovascular and
      other treatments and less to respiratory life sustaining treatment. Artificial
      nutrition and hydration were rarely withdrawn.

PMID- 16972584
TI  - Outcome of accident and emergency room triaged patients with low risk non
      variceal upper gastrointestinal haemorrhage.
AB  - An acute upper gastrointestinal haemorrhage (UGIH) is an expensive healthcare
      problem estimated to cost more than 2.5 billion dollars per annum in the United
      States. Recent British Society of Gastroenterology (BSG) guidelines (2002) advise
      that patients with low risk non variceal UGIH have a benign outcome and may be
      suitable for a relatively short hospital stay with attendant economic saving. We
      evaluated current clinical experience, endoscopy findings and length of hospital
      stay in our hospital. We carried out a two year retrospective data analysis of
      395 Accident and Emergency Room triaged patients admitted with a low risk non
      variceal UGIH. Data variables included age, sex, presence of co morbid illness,
      endoscopic findings, Rockall Risk Score, mortality within the hospitalisation
      period and length and cost of hospital stay. Of the 395 haemodynamically stable
      patients identified, requiring 1,644 hospitalisation days, 320/395 (85.8%) had a
      Rockall Score < or =3. No endoscopic intervention was required in 366/395 (92.7%)
      of patients with a 2% overall mortality. The mean hospital length of stay (LOS)
      was 4.16, costing in excess of 1002,840 Euro. Following routine clinical practice
      for low risk non variceal UGIH, the subsequent duration of hospital stay was
      unnecessarily prolonged and costly. This highlights the need to initiate change,
      to monitor resource utilisation and implement early hospital discharge in
      appropriate patients.

PMID- 16972585
TI  - The burden of alcohol misuse on the emergency department.
AB  - This study had two objectives. To assess the impact of alcohol-related problems
      on the Emergency Department (ED) of Cork University Hospital (CUH). To assess the
      non-acute impact of alcohol-related problems on CUH. One hundred patient ED
      records were chosen at random from each of three study periods--December 23rd
      2002 to January 2nd 2003, April 20th 2003 to April 30th 2003, and December 23rd
      2003 to January 2nd 2004. Each patient record was examined individually to
      determine the rate of alcohol-related attendances at CUH ED. Overall, alcohol
      related attendances accounted for 14.66% of ED attendances. 22.73% of these
      patients were admitted and 27.27% received an out-patient department appointment.
      The results of this study were broadly in keeping with previous large-scale
      studies; it is clear that alcohol-related attendances, admissions and OPD
      appointments are putting a large strain on EDs and the whole hospital system.

PMID- 16972586
TI  - Minor head injuries in children.
AB  - Traumatic head injury continues to be a major problem facing the pediatric
      specialists despite efforts to reduce its incidence. Aims of our study were
      assessment of the incidence of hospital admissions of children with minor head
      injuries, their treatment and outcome. In this prospective study we included 101
      patient with head injury. We assessed the hospital admission criteria of children
      with minor head injuries, their length of stay, symptoms and neurological status,
      in-hospital imaging and consultations to other medical specialities, together
      with the outcome of patients on their discharge from the hospital. Of 101 patient
      54 (53.46%) were male and 47 (46.53%) female. Average age was 3 years with age
      range from 5/52 to 12 years. Majority of patients (46.53%) were less than 1 year
      old. Fall was the most common mechanism of injury (92.07% of all patients).
      Injuries were witnessed in 51 case (50.49%), unwitnessed in 19 cases (18.81%) and
      unknown in 31 cases (30.69%). 95 patients did not have associated extracranial
      injuries, while 5 patients had associated lacerations and one had associated
      extracranial fracture. Length of stay was from 1 day in 80.19% of all cases to
      more than 2 days in 6.93%. GCS was recorded on admission and discharge and
      majority of patients were discharged with GCS of 15. 93% of admissions had no
      neurological deficit. 79% had 1 or more symptoms including vomiting, sleepiness,
      LOC and headaches. Over half of patients (55%) had no imaging done. 45 patients
      (45%) had skull x-ray. CT was performed in 7 (15%) patients and 7 fractures were
      found on x-ray and CT. 3 patients were admitted to ICU. All injuries were closed
      and all received conservative treatment. In less than 1 year old group of
      patients 95% of them were also seen by medical team and social worker. The
      outcome was good for all patients. We conclude that majority of patients with
      minor head injury could be supervised and observed at home by a competent care
      giver. Admitted patients need radiological evaluation, preferably a CT scan.

PMID- 16972588
TI  - Uterine adenocarcinoma.

PMID- 16972587
TI  - Acceptability of routine enquiry regarding domestic violence in the antenatal
      clinic.
AB  - Domestic Violence poses a significant health risk for the woman and her baby. We
      wished to determine the acceptability of routine questioning for domestic
      violence in the maternity hospital setting. A non-anonymised questionnaire was
      completed by 481 women attending for booking antenatal appointment in a maternity
      hospital antenatal clinic. The doctor asked four questions regarding experience
      of partner abuse, The acceptability of these questions was determined. 468 (99%)
      patients found the questions acceptable and said it would be helpful to ask all
      patients. Sixty-one (12.9%) women gave a history of at least one form of partner
      abuse. We concluded that routine enquiry about domestic violence during hospital
      antenatal visits is acceptable to women and perceived by them to be worthwhile.

PMID- 16972589
TI  - Anaphylaxis following paediatric immunization.

PMID- 16972590
TI  - [Comparative assessment of cognitive styles forming personal behavior in health
      and borderline personality disorder].
AB  - The author suggests a cognitive-analytical concept of personality focusing on
      cognitively mediated processes of cyclic interaction of different levels of
      consciousness and subconsciousness represented in the form of emotional
      behavioral potential and functional-dynamic system. A cognitive type (cognitype)-
      a type of personality-centered cognitive operations that determines the pattern
      of behavioral cycle and distinctive features of social adaptation--is singled out
      as an integrative basic individual and psychological component of personality.
      Presented is classification of personality cognitypes, their adaptive and
      maladaptive variants, correlations between cognitypes and anomalies of
      personality. The principles of psychotherapy of maladaptive behavior, borderline
      and addictive disorders (positive reintegration of personality) are
      substantiated.

PMID- 16972591
TI  - [The variants of personality maladaptation in patients with multiple sclerosis].
AB  - Thirty-four patients with multiple sclerosis (MS), aged 14-52 years, age-at
      disease-onset 24,3 +/- 7,5 years, have been studied. Disease severity score
      measured with the Kurtzke scale (EDSS) was 3,6 +/- 1,7. Seven patients were at
      the exacerbation stage, 27--in remission. Personality features in context of its
      maladaptation were studied using a modified version of MMPI. Neurotic, psychotic
      and mixed types of maladaptation have been singled out. The positron emission
      tomography indices of metabolic brain activity by glucose metabolism rate were
      concurrently determined. Data on the complementarity of metabolic processes
      activity in frontal, temporal-parietal and limbic cortical areas with different
      variants of personality maladaptation and different MMPI personality profiles
      were obtained.

PMID- 16972592
TI  - [Clinical and psychological features of children with agenesis of the vermis
      cerebelli].
AB  - The article considers behavioral disturbances in children with anomalies of the
      cerebellum found by MRI studies. Presented are literature data on the relations
      between pathology of the cerebellum and early autism in children. The cerebellum
      is involved not only in movement coordination but also in social adaptation and
      speech communication. Cerebellum-specific genes expressed in early age are
      similar to those of hippocampus. Our own study of children with agenesis of the
      vermis cerebelli detected by MRI and behavioral disturbances included 20 children
      aged 3-15 years (mean age 7,05 years, 12 male, 8 female). Some autistic features
      have been found.

PMID- 16972593
TI  - [Depressive disorder with pathological body sensations].
AB  - A group of patients with depressive disorder, depressive episode (DE) according
      to the ICD-10, with episodic or recurrent course and the presence of pathological
      body sensations (PBS) in the form of senestoalgic, senestoalgic-senestopathic and
      senestopathic syndromes has been studied. The study group consisted of 65
      patients with PBS and the control one--of 30 patients without PBS. More than a
      half of patients with DE and PBS had severe DE without psychotic symptoms.
      Modality of hypothymia was assessed by depressed mood with presence/absence of
      melancholy and permanent anxiety appearing as generalized anxiety disorder. The
      study group was divided into 2 subgroups: DE with monolocal (39 patients) and DE
      with bi- or polylocal (26 patients) PBS. Initial, manifest and active stages of
      the disease course were singled out and PBS dynamics and appearances of
      depressive disorders per se on each stage were studied. The presence of comorbid
      disorders such as panic disorder (full and symptomatically poor variants) was
      found. Continuum is suggested in manifestations of monopolar depression as a
      borderline variant of affective psychosis: depression without PBS--depression
      with bi- and polylocal PBS--depression with monoclonal PBS.

PMID- 16972594
TI  - [Batroxobin in patients with ischemic stroke in the carotid system (the
      multicenter study)].
AB  - A randomized placebo-controlled study has been carried out in 3 Moscow hospitals.
      A sample included 90 patients who survived hemispheric ischemic stroke caused by
      pathology in the internal carotid artery 72 h before the treatment. Forty-five
      patients were given standard (basic) therapy and 45 patients received adjuvant
      batroxobin intravenously by 1,0 ml (10BU) drops on day 1, 3 and 5 and by 0,5 ml
      (5BU) drops on day 7 and 9 after admitting in a hospital. Assessment of the
      patients' state was conducted before the treatment, on day 3, 6 and 15. The
      European Stroke Scale was used to measure severity of clinical symptoms. The
      results suggest efficacy of batroxobin the use of which provides rapid good
      results, especially improvement in movement disorders. The use of this drug is
      accompanied by defibrinating effect. The drug is well tolerated.

PMID- 16972595
TI  - [Reproductive dysfunctions in female patients during therapy with atypical
      antipsychotics].
AB  - To specify interrelations between clinical and hormonal aspects of reproductive
      dysfunctions appearing during therapy with atypical antipsychotic agents
      (clozapine, olanzapine, quetiapine), 131 female patients with paranoid
      schizophrenia and schizoaffective disorder have been studied. Distinctive
      features of dynamics of prolactin as well as hypothalamic-pituitary-gonadal
      hormones levels for each medication studied and correlations between hormone
      indices and clinical presentations of reproductive dysfunctions (galactorrhea,
      disturbances of menstrual cycle and libido) were found.

PMID- 16972596
TI  - [Diagnosis and treatment of moderate cognitive disorders in the elderly].

PMID- 16972597
TI  - [Autoantibodies to glutamate receptors in children with chronic posttraumatic
      headache].
AB  - Autoantibodies (aAB) to AMPA (Glu R1 subunit) and NMDA (NR 2A subunit) glutamate
      receptors were studied in blood serum of 60 children, aged 7-16 years, with
      chronic posttraumatic headache after mild skull injury. All the children were
      divided into 2 groups: group 1 included 48 children with concussion of the brain,
      group 2--12 children with brain contusion. Group 1 was divided into 2 subgroups:
      subgroup 1a comprised 34 children with single concussion and subgroup 1b--14
      children with repeated concussion. The aAB level was determined 6 months and 1
      year after skull injury. The aAB concentration was expressed in percents to the
      control level being considered significant if the increase was higher than 120%.
      The increased NMDA aAB level was observed during the first year after skull
      injury. In the la subgroup, the NR2 aAB level in blood serum was 145 +/- 12,6%,
      in the 1b one--108 +/- 12,4%, in group 2--165 +/- 34%. The content of aAB to AMPA
      receptors was elevated only in children of lb subgroup and group 2 (150 +/- 16,8%
      and 167 +/- 31,3%, respectively). The EEG examination of this group revealed the
      nonspecific paroxysmal discharges in 18% of cases and epileptiform activity in 6%
      of children. The results obtained suggest that children with posttraumatic
      headache have elevated levels of aAB to glutamate receptors, hyperstimulation of
      which reflects hypoxic processes in the brain, and are in need of metabolic
      therapy.

PMID- 16972598
TI  - [Leucocytes' ability to accumulate and secrete cholesterol is a nonspecific
      factor of immune inflammation in patients with atherothrombotic stroke].
AB  - The aim of the study was investigation of nonspecific inflammation markers in
      atherosclerotic injury of major arteries of the head (MAH). A complex study,
      including duplex ultrasonography, CT, measurement of cholesterol and its
      fractions, has been conducted in 85 patients with atherothrombotic (72 patients)
      and lacunar (23 patients) stroke. The ability of leucocytes' culture to
      accumulate and secrete cholesterol in vitro was studied as a nonspecific
      inflammatory marker of lesion of atherosclerotic MAH. A high level of this index
      was characteristic of atherothrombotic type of stroke comparing to lacunar stroke
      and the control group. Furthermore, high levels of this index correlated with
      severity of atherosclerotic injury of MAH, in particular with plaques. The
      dynamics of the index after 24-day therapy by statins (vasilip) is presented. We
      suppose that the protective influence of statins in patients after ischemic
      stroke may be caused by the effects on the level of immune competent cells
      including reducing leucocytes ability to accumulate and secrete protein-lipid
      complexes.

PMID- 16972599
TI  - [The experience in surgical treatment of Gilles de la Tourette's syndrome].

PMID- 16972600
TI  - [Stabilometry parameters in some mental disorders].

PMID- 16972601
TI  - [Somatic and neurological disorders in psychoactive substance addiction].

PMID- 16972602
TI  - Interior design specialist--Adding another member to the interdisciplinary team.

PMID- 16972603
TI  - Post-hospital transition to a skilled nursing facility--Compliance, competence,
      and communication.

PMID- 16972604
TI  - Clinical competencies--Caring for late-life depression in home care patients.

PMID- 16972605
TI  - Living alone: the choice and health of older women.
AB  - Contrary to the stereotype of being dependent and emotionally unstable, and
      unable to contribute to society, older women living alone are psychologically
      secure in their well-being and are happy about being independent. Nurses are
      encouraged to understand personal perceptions of older women when providing care
      for these individuals. Studies of diverse cultures and ethnicities are needed to
      build knowledge about older women living alone.

PMID- 16972606
TI  - Assessing the mental health of rural older adults in public housing facilities: a
      comparison of screening tools.
AB  - This pilot study assessed the prevalence of mental health disorders and cognitive
      impairment among rural older adults living in a public housing facility and
      compared screening tools in this setting. Interviews were completed with 20 of
      the 38 residents older than 60 years. Survey instruments included the following:
      Primary Care Evaluation of Mental Disorders (PRIME-MD), Medical Outcomes 36-item
      Short-Form Health Survey (SF-36), Montgomery-Asberg Depression Rating Scale
      (MADRS), Mini-Mental State Exam (MMSE), and Global Assessment Scale (GAS).
      Depressive disorders were identified in 50% (n = 10) of participants and included
      major depression (25%), minor depression (20%), and dysthymia (5%). Cognitive
      impairment was identified in 15% (n = 3) of participants. Comparative analysis of
      instruments administered showed high correlations among the PRIME-MD, MADRS, GAS,
      and SF-36. The screening instruments identified for depression and cognitive
      impairment can be used reliably by nurses in this setting.

PMID- 16972607
TI  - Transition of new residents to long-term care: basing practice on residents'
      perspective.
AB  - Admission to a long-term care facility is a time of disorganization and
      adaptation. New residents experience transition breakdown beginning with a sense
      of homelessness as they learn the rules of institutional living. With the passage
      of time, residents may be able to create a place of their own. Story sharing is
      an important way to help new residents integrate into the unfamiliar long-term
      care facility.

PMID- 16972608
TI  - The influence of growth on spiritual self-care agency in an older adult
      population.
AB  - This study investigated the relationships among health-promoting self-care
      behaviors, self-care self-efficacy, and self-care agency in an older adult
      population. The purpose of this study was to identify the relationships among
      these concepts as well as the specific influence of spiritual growth, a component
      of health-promoting self-care behaviors, on self-care agency. The instruments
      used in this study included the Health-Promoting Lifestyle Profile II, Self-Rated
      Abilities for Health Practices Scale, and Exercise of Self-Care Agency Scale. A
      canonical correlation identified a significant variate having a correlation of
      .74 (p = .000) that accounted for 55% of the variance explained. The loading
      variables included spiritual growth, self-concept, initiative, and
      responsibility. The conclusion was made that spiritual growth influences older
      adults' self-care agency to a greater extent than self-care self-efficacy.

PMID- 16972609
TI  - Frances Hains--painting her way through loss.

PMID- 16972611
TI  - [Clinical evaluation of bird related hypersensitivity pneumonitis].
AB  - We retrospectively evaluated 8 cases of bird related hypersensitivity pneumonitis
      in Tenri hospital, all of whom underwent surgical lung biopsy. They had a history
      of contacting with birds and had serological studies using lymphocyte stimulation
      test to pigeon serum or antibody in serum and bronchoalveolar lavage fluid to
      pigeon dropping extracts yielded positive results. Computed tomography revealed a
      radiographic pattern unlike typical UIP. The result of pathological diagnosis of
      surgical lung biopsy was 'others' or NSIP pattern. Only one case had pathological
      findings of granuloma. Four cases had an improved or stable course only offer
      segregation from bird antigens. The other four cases needed corticosteroids and
      immunosuppressants, and two of the four cases had a progressive course and died
      of respiratory failure.

PMID- 16972610
TI  - [In order to perform clinical trials efficiently in Japan--important issues in
      medical institutions raised by the GCP on-site review].
AB  - The guidelines for Good Clinical Practice (GCP) in Japan have been harmonized
      with ICH-GCP. Both the protection of human rights and the carrying out of
      clinical trials ethically and scientifically, conforming to the GCP, are
      necessary for the safety and efficacy of clinical data of common technical
      documents. It is standard practice in Japan, the U.S., and the E.U. to ensure
      conformity with all data from raw data to application materials. In April, 2004,
      the new independent organization Pharmaceuticals and Medical Devices Agency
      (PMDA) was established in Japan. The PMDA provides services focusing on the three
      key areas of Review, Safety, and Relief. The Office of Conformity Audit is one of
      the offices in the Center for Product Evaluation of the PMDA. In the conformity
      audit service of the Office of Conformity Audit of the PMDA, the reliability and
      conformity with the GCP between case report forms (CRFs) as basis materials and
      application materials is confirmed by the document-based conformity review, and
      the conformity between medical records as raw data and CRFs is assessed through
      the on-site GCP review. Therefore, such application materials are considered to
      be consistent with international standards. The important issues raised by the
      GCP on-site review by the Office of Conformity Audit of the PMDA are summarized
      in this study. We hope that our findings at investigational sites will promote
      the protection of human rights and improve the quality of clinical trials in
      Japan.

PMID- 16972612
TI  - [A clinical study of advanced large cell neuroendocrine carcinoma].
AB  - Large cell neuroendocrine carcinoma (LCNEC) is a newly recognized
      clinicopathologic entity. The clinical features of advanced LCNEC are still
      unclear, because most of the previous reports have described resected cases. The
      aim of this study was to clarify the clinical characteristics and response to
      chemotherapy in patients with advanced LCNEC. From June 2002 to July 2004, nine
      patients (seven men and two women, median age 61) with advanced LCNEC were
      admitted to our hospital. We reviewed the clinical manifestations, tumor markers,
      and treatment of these patients. Seven of nine patients (78%) were current or ex
      smokers. As for tumor markers, the levels of progastrin-releasing peptide
      (proGRP) and neuron-specific enolase (NSE) were elevated in six patients (67%)
      and five patients (56%), respectively. The diagnosis of LCNEC was made based on
      the resected specimens in 8 patients including resection of brain metastasis in 1
      and CT-guided needle biopsy in 1. One patient was stage IIIA, 1 was stage IIIB, 3
      were stage IV, and 4 had postoperative recurrence. Treatment included
      chemotherapy alone in 7 patients, chemotherapy plus whole brain radiation in 1,
      and postoperative radiotherapy in 1. Of 7 patients treated by chemotherapy alone
      who had received carboplatin-based chemotherapy. 5 showed partial response,
      yielding response rate of 71.4%. The proGRP level was frequently elevated in
      patients with advanced LCNEC and the response rate of LCNEC to carboplatin-based
      chemotherapy was comparable to that of small cell lung cancer.

PMID- 16972613
TI  - [A case of pulmonary abscess in which Haemophilus parainfluenzae and
      Streptococcus intermedius were isolated by percutaneous needle aspiration].
AB  - Some microbes, including the Bacteroides species, Staphylococcus aureus and
      Streptococcus milleri groups, can cause pulmonary abscess. Haemophilus
      parainfluenzae is usually categorized as one of the normal flora which colonizes
      in the ears and the nasopharynx, and it has been long considered that H.
      parainfluenzae has little pathogenicity in the lower respiratory tract and lung
      parenchymal. In this report, we present a case of pulmonary abscess caused by
      both H. parainfluenzae and Streptococcus intermedius. The patient was a 75-year
      old man who had had total esophageo-gastrectomy because of esophageal cancer. He
      presented with purulent sputum, and chest X-ray film showed a dense consolidation
      in the right upper lung field. CT-guided transcutaneous fine needle aspiration
      was performed as a diagnostic procedure. Since both H. parainfluenzae and S.
      intermedius had been isolated from the lesion, pulmonary abscess caused by these
      two pathogens was diagnosed. The patient was treated with panipenem/betamipron,
      and his symptoms and pulmonary infiltrates on the chest X-ray film improved
      thereafter. So far, very few cases have been reported in which H. parainfluenzae
      caused lower respiratory tract infection. Although S. intermedius is known as one
      of the pathogens of pulmonary abscess, it is possible that H. parainfluenzae
      could also be pathogenic in infectious diseases of the lung.

PMID- 16972614
TI  - [A case of systemic sarcoidosis diagnosed initially by tonsillar biopsy, with
      discontinuous nodules in a straight line in the subcutaneous tissue of the upper
      arm].
AB  - A 31-year-old woman was admitted due to swollen cervical lymph nodes and swollen
      tonsils. These did not respond to treatment by antibiotics, and histological
      findings of epithelioid cell granulomas were obtained by tonsillar biopsy. After
      corticosteroid therapy in the subcutaneous tissue of the upper arm 5 nodules were
      found discontinuously in a straight line. A biopsy of one of these nodules
      revealed non-caseous epithelioid cell granuloma with Langhans giant cells in the
      superficial lymph nodes. Her older brother was strongly suspected to have
      neurogenic sarcoidosis. Familial sarcoidosis was considered related to this case.

PMID- 16972615
TI  - [A case of multiple lung abscesses successfully treated with computed tomography
      guided percutaneous thoracic drainage].
AB  - A 48-year-old woman who had abused alcohol admitted to our hospital because of
      fever and chest pain. Laboratory data presented inflammation and liver
      dysfunction. Chest X-ray films revealed multiple mass lesions with air fluid
      levels. We diagnosed multiple lung abscesses and started treatment with
      antibiotics. However, her fever did not improve and mass lesions increased. On
      day 6 of hospitalization, three drainage tubes were inserted percutaneously into
      the mass lesions under computed tomography (CT) guidance, and alpha-hemolytic
      streptococcus, peptostreptococcus sp. and neutrophils were isolated from the
      drainage fluid. Abcesses and inflammation were improved by administration of the
      antibiotics selected according to the result of fluid culture. Because all
      multiple abcesses were located near the pleura, we successfully treated them with
      simultaneous percutaneus thoracic drainage.

PMID- 16972616
TI  - [A case of sho-seiryu-to-induced pneumonia with a marked increase in peripheral
      eosinophils].
AB  - A 25-year-old woman presented with a high temperature, cough and dyspnea three
      days after taking sho-seiryu-to, a Chinese herbal preparation, for a cough and
      throat pain. A chest X-ray film and computed tomography (CT) scan revealed
      diffuse infiltrative shadows in both the middle and lower lung fields. Arterial
      blood gas analysis showed hypoxemia (PaO2 43Torr under room air). The white cell
      count was 40,800/mm3, with eosinophilic cells accounting for 56.5% of the cells.
      The patient was treated with methylprednisolone under a diagnosis of drug-induced
      pneumonia and the administration of sho-seiryu-to was discontinued. Immediately
      after the prednisolone administration, her chest X-ray film findings, clinical
      symptoms and laboratory data markedly improved. A lymphocyte stimulation test for
      sho-seiryu-to using peripheral lymphocytes was positive. In 29 cases of herbal
      medicine-induced pneumonia reported in Japanese medical literature over a 10-year
      period, sho-saiko-to has been the predominant cause of drug-induced pneumonia.
      This is the second case of sho-seiryu-to-induced pneumonia.

PMID- 16972617
TI  - [A case of systemic amyloidosis treated by chemotherapy with autologous
      peripheral blood stem cell transplantation].
AB  - A 67-year-old woman was admitted to our hospital because of breathlessness.
      Systemic amyloidosis had been diagnosed 5 years previously. Her chest X-ray film
      showed multiple nodules in both lung fields. Chest computed tomography (CT)
      revealed some of the nodules had calcifications. Bronchoscopy demonstrated
      amyloid deposits in the bronchial walls. The serum titer of anti-SS-A antibody
      was high. Results of both the Schirmer Test and the Rose-Bengal Test were
      positive. The final diagnosis was systemic amyloidosis with Sjogren's syndrome.
      She was treated by chemotherapy using high dose melphalan with autologous
      peripheral blood stem cell transplantation (PBSCT). It was obvious that her chest
      X-ray film findings and bronchoscopic findings had improved 9 months after high
      dose chemotherapy with PBSCT. The disappearance of M protein and improvement of
      thirst, a symptom of Sjogren's syndrome, were also observed.

PMID- 16972618
TI  - [A case of AIDS-complicated lung infection mimicking acute eosinophilic
      pneumonia].
AB  - A 34-year-old man was admitted with dyspnea and low grade fever. Chest radiograph
      and computed tomography (CT) showed bilateral, ground glass opacities and
      perihilar consolidation. Bronchoalveolar lavage (BAL) was performed. The
      percentage of eosinophils in the BAL fluid (BALF) was elevated (20.5%). BALF
      smear and culture showed normal flora. Acute eosinophilic pneumonia was diagnosed
      and steroid therapy was performed. Afterwards he was transferred to our hospital.
      The HIV antibody was positive and peripheral blood CD-4 positive lymphocytes
      decreased to 10/microl, cytomegalovirus (CMV) antigenemia was positive and beta-D
      glucan increased. CMV infection and pneumocystis pneumonia (PCP) complicated with
      AIDS was diagnosed. Trimethoprim/sulfamethoxazole, ganciclovir, and antifungal
      drugs were administered, but he suffered pneumothorax on the 18th day after
      admission and died. Histopathologic findings from an autopsy lung specimen
      revealed CMV infection and PCP. It is known that the percentage of eosinophils in
      the BALF increases in some cases of PCP complicated with AIDS. We emphasize that
      it is necessary to consider PCP when the percentage of eosinophils in the BALF
      increase.

PMID- 16972619
TI  - [Three cases of chronic bird fancier's lung associated with the use of feather
      bedclothes].
AB  - We report here 3 cases of chronic bird fancier's lung diagnosed immunologically
      using antibodies to pigeon dropping extract. None of the patients were bird
      fanciers but had indirect exposure to birds in their living environment, and had
      been using feather-filled duvets or pillows for a long time. Two of 3 cases were
      positive for environmental provocation tests and 2 cases had pathological
      findings of hypersensitivity pneumonitis such as multinucleated giant cells and
      non-necrotizing epithelioid cell granulomas. One case was resistant to steroid
      therapy alone and was successfully treated by coadministration of prednisolone
      and cyclosporin A. Another case was treated by steroid alone but died of acute
      exacerbation of unknown cause. These cases suggest that not only feathers but two
      or more kinds of bird-related antigens were involved in the sensitization
      immunology and development of bird fancier's disease, and that clinicians should
      perform thorough history taking with environmental surveillance relevant to
      birds.

PMID- 16972620
TI  - [A case of spontaneous epidural emphysema occurring during sleep].
AB  - A 19-year-old man consulted a doctor for swelling of his neck and shortness of
      breath. The day before, he woke up with a slight cough and upper chest pain early
      in the morning. He went to school and spent the day as usual. He did not have a
      history of asthma or violent cough. The next day, chest radiography showed
      subcutaneous emphysema and pneumomediastinum. Computed tomography not only
      confirmed the presence of mediastinal and subcutaneous air, but also demonstrated
      a linear radiolucent stripe in the spinal canal corresponding to epidural
      emphysema. The patient did not have any neurologic findings. His general
      condition remained good except that his arterial blood oxygen saturation slightly
      decreased to 95%. Laboratory data were normal, except for serum IgE, which was
      elevated (2072 IU/ml). He stayed at rest and was treated conservatively and his
      symptoms improved within a few days. Seven days later, the intraspinal air and
      pneumomediastinum had resolved spontaneously on follow-up chest computed
      tomography (CT).

PMID- 16972621
TI  - Long-term outcome from a study on the prevention of postoperative recurrence in
      patients with renal cell carcinoma: could PBL be a predictor of postoperative
      recurrence in patients postoperatively treated with IFN-gamma?
AB  - This study examined the outcome of postoperative recurrence therapy on renal cell
      carcinoma (RCC) prevention involving treatment with single doses of interferon
      gamma (IFN-gamma). From 1990-2000, 37 patients with no distant metastasis at the
      time they underwent a nephrectomy were enrolled in this investigation.
      Subcutaneous IFN-gamma was administered once a week. Total and differential white
      blood cells were counted before the pre-administration of IFN-gamma and then
      monthly thereafter for all patients. Blood lymphocyte subsets were analyzed
      phenotypically by direct immunofluorescence. Disease-free survival rates (DFSR)
      at 5 and 10 years were 81.7% and 75.9%, respectively. To clarify the effects of
      preoperative peripheral blood lymphocyte (PBL) and NK activity on DFSR, we
      categorized the patients into two groups according to the median number of PBL
      before the administration of IFN-gamma. Except for CD11b, PBL level had no effect
      on DFSR. Multiple logistic regression analysis showed that CD11b levels greater
      than 16.5% were associated with 25.35 odds ratio increase in the risk of
      postoperative recurrence. A multivariate analysis found that CD11b may be an
      independent factor for postoperative recurrence. In terms of preventing
      postoperative recurrence, our results showed that an elevated CD11b level may
      indicate patients who can benefit from further combination therapy.

PMID- 16972622
TI  - [A study of 4,031 patients of transurethral resection of the prostate performed
      by one surgeon: learning curve, surgical results and postoperative
      complications].
AB  - A total of 4,031 patients who underwent transurethral resection of the prostate
      (TURP) performed by one surgeon between May 1979 and December 2003 were
      retrospectively examined to determine the improvement of the surgeon's skill in
      performing TURP assessed by using a learning curve, surgical results and
      postoperative complications. Analysis using the learning curve, which displayed
      the relationship between the number of TURP procedures and the speed of resection
      (i.e., the weight of tissue resected divided by the operation time), revealed
      that 81 operations were needed before the surgeon's skill reached a plateau in
      performing TURP. The means +/- standard deviations of the weight of tissue
      resected, operation time and speed of resection were 17.0 +/- 14.6 g, 21.0 +/-
      13.5 minutes, 0.80 +/- 0.32 g/minutes, respectively. As the number of TURP
      procedures increased and the level of skill improved, the operation time was
      significantly reduced and the speed of resection was significantly increased. The
      incidences of postoperative complications were 2.4% for blood transfusion, 0.3%
      for the TURP syndrome, 1.5% for hemostatic procedures, 2.8% for bladder neck
      contracture, and 1.0% for urethral stricture. The incidences of transfusion and
      the TURP syndrome decreased as the surgeon's skill improved. The mortality rate
      was 0.1%.

PMID- 16972623
TI  - [The Aging Male's Symptoms (AMS) scale in Japanese men attending an infertility
      clinic].
AB  - There is a gradual decline in testosterone and free testosterone with age.
      Physical and psychological changes can occur due to this decline of androgens--a
      syndrome known as "partial androgen decline in the aging male" (PADAM). Male
      infertility and erectile dysfunction (ED) can also be caused by androgen
      deficiency. Thus, male infertility, ED and PADAM are interrelated. We evaluated
      the prevalence of PADAM symptoms in 215 infertile patients in an infertility
      clinic using the Aging Males Symptom (AMS) scale. Results of the evaluation of
      301 men, (30-39 years old) using the same scale, who were part of a multiphasic
      health screening program, served as controls. The total score of the infertile
      patients was lower than that of the controls. Especially, the scores of the
      psychological and somatic subscales were significantly lower in infertile
      patients (P=0.009, P=0.012, respectively). Thirty three (15.3%) of the 215
      infertile patients had ED. Although the score of sexual subscale was higher in
      the ED patients than in the controls, the scores of the psychological and somatic
      subscales were not significantly different from those in the controls. In
      conclusion, PADAM symptoms in Japanese infertile patients were not severe.
      Moreover, general function was better preserved in the infertile patients than in
      the controls. The psychological and somatic functions of ED patients were also
      well preserved.

PMID- 16972624
TI  - [Adrenal ganglioneuroma in a 14-year-old girl: a case report].
AB  - A 14-year-old girl was referred to our hospital for examination of a right
      adrenal tumor, incidentally found by abdominal ultrasound sonography. Computed
      tomographic scan and magnetic resonance imaging showed a 44 x 20 mm solid tumor
      in the right adrenal region. Endocrinological examination were within normal
      limits except for slightly increased serum aldosterone. Laparoscopic
      adrenalectomy was performed and the tumor was histologically diagnosed as
      ganglioneuroma originated from the right adrenal medulla.

PMID- 16972625
TI  - Usefulness of positron emission tomography (PET) in a retroperitoneal primary non
      seminomatous germ cell tumor: a case report.
AB  - A 32-year-old Japanese man was admitted complaining of palindromic fever and
      abdominal pain. Computed tomography (CT) revealed retroperitoneal mass and
      positron emission tomography (PET) demonstrated massive radiotracer uptake in
      this tumor. Serum levels of alpha-fetoprotein (AFP) and human chorionic
      gonadotropin (hCG) were 4,760 ng/ml, 6,000 mIU/ml, respectively. Biopsy specimen
      from the tumor showed non-seminomatous germ cell tumor. The International Germ
      Cell Cancer Collaborative Group (IGCCCG) staging system indicated this case as an
      intermediate prognosis group. After three cycles of bleomycin, etoposide and
      cisplatin (BEP) therapy, CT revealed a degenerated residual mass. Serum levels of
      tumor markers were normalized completely and PET showed no radiotracer uptake in
      the retroperitoneal lesion. Although he did not receive further chemotherapy and
      lymph nodes were not dissected, he was free of disease for two years.

PMID- 16972626
TI  - A case of TURBT after penile prosthesis implantation.
AB  - The patient was a 66-year-old man who had undergone implantation of a penile
      prosthesis for organic erectile dysfunction 7 years prior to consulting our
      hospital with a complaint of gross hematuria. Since a pedunculated, superficial
      tumor 1 cm in diameter was noted lateral to the left ureteral orifice,
      transurethral resection of the bladder tumor (TURBT) was performed. In this
      patient, we were able to insert the sheath with no difficulty, and the surgical
      procedure was done smoothly, resulting in complete resection of the tumor.
      However, the location of the tumor in the anterior or posterior wall of the
      bladder predicted difficulty of the tumor resection. Therefore, we consider it
      important to sufficiently evaluate the feasibility of complete TURBT before
      surgery and to thoroughly examine the patient for benign prostatic hyperplasia
      and bladder cancer, which can cause difficulty with post-implantation
      ransurethral procedures, and to perform transurethral surgery before
      implantation, if prosthesis implantation is planned.

PMID- 16972627
TI  - [A case report: small cell carcinoma transformed from transitional cell carcinoma
      of the urinary bladder].
AB  - A 72-year-old man presented with gross hematuria. Cystoscopy showed a non
      papillary tumor at the right side of the posterior wall. Transurethral resection
      of the bladder tumor (TURBT) was performed. Pathologic findings demonstrated
      superficial transitional cell carcinoma (TCC). However, recurrent tumors were
      detected at the same location after 69 months' follow up. TURBT was done for the
      biopsy and pathologic examination showed muscle-invasive TCC. After two courses
      of neoadjuvant chemotherapy (MVAC), we performed radical cystectomy with
      Hautmann's continent reservoir. Pathologic findings revealed small cell carcinoma
      without any TCC features. Immunohistochemical staining using chromogranin A and
      synaptophysin was positive in the latest TURBT and the radical cystectomy
      specimens. We report a case of primary small cell carcinoma transformed from TCC
      of the urinary bladder.

PMID- 16972628
TI  - [A case of ureteral carcinoma at 11 years after radical cystectomy and rectal
      bladder reconstruction: a case report].
AB  - We report a 74-year-old male who developed ureteral carcinoma after 11 years of
      radical cystectomy and rectal bladder reconstruction. The patient had right
      lumbago and high grade fever and right hydronephrosis. He was suspected to have
      right ureter tumor under the antegrade pyelography at the time of right
      nephrostomy, and ureter tumor was diagnosed by the combination of computed
      tomography and antegrade pyelography. Under this preoperative diagnosis, right
      nephroureterectomy was performed. The histopathological diagnosis was
      transitional cell carcinoma. Since the recurrence of urothelial cancer at 10
      years after radical cystectomy is rare, we believe our case is useful for the
      establishment of long-term follow up of bladder cancer.

PMID- 16972629
TI  - [Pyogenic spondylitis by Enterobacter cloacae as a postoperative complication of
      TURP: a case report].
AB  - We report a case of pyogenic spondylitis caused by Enterobacter cloacae as a rare
      complication of transurethral resection of the prostate (TURP). A 79-year-old man
      underwent TURP. Immediate after removal of urethral catheter on postoperative day
      (POD) 7, he developed high fever > 40 degrees C with increased acute inflammatory
      reaction. Urine and blood culture detected E. cloacae and methicillin-resistant
      Staplylococcus aureus. He complained of lumbago since POD 9. Two-week
      administration of imipenem and teicoplanin resulted in resolution of fever as
      well as laboratory data, so intravenous antibiotics were changed to oral
      gatifloxacin. However, his lumbago worsened and gait disturbance appeared. On POD
      39, diagnosis of pyogenic spondylitis was finally obtained by Ga-scintigraphy and
      magnetic resonance imaging. Aspiration of the intervertebral disk (L4-5) revealed
      E. cloacae as the causative organism of pyogenic spondylitis. His condition
      improved after conservative treatment with teicoplanin, meropenem and
      ciplofloxacin for 9 weeks.

PMID- 16972630
TI  - [Sepsis following transrectal prostate biopsy: a report of 2 cases and reviewed
      similar cases in Japan].
AB  - We report two cases of sepsis and disseminated intravascular coagulation (DIC),
      potentially fatal complications, following transrectal prostate biopsy. We also
      review similar cases reported in Japan. Case 1: A 63-year-old man received a
      cathartic and levofloxacin (LVFX) for prophylaxis. After transrectal prostate
      biopsy, he presented with fever and chills. Blood cultures grew Escherichia coli
      resistant to LVFX. Under a diagnosis of sepsis, he received intensive management
      that included endotoxin removal therapy. The patient was hospitalized for 27
      days. Case 2: A 64-year-old man received a cathartic and cefazolin (CEZ) for
      prophylaxis. He presented with fever and chills after biopsy, and was admitted to
      hospital. Blood cultures grew E. coli resistant to CEZ. Under a diagnosis of
      sepsis, he received intravenous antibiotics, transfusion, and anti-DIC drugs. The
      patient was hospitalized for 11 days.

PMID- 16972631
TI  - [A non-seminomatous extra-gonadal germ cell tumor responding to intensive
      treatment: a case report].
AB  - A 23-year-old man presented with lumbago as a chief complaint. Computed
      tomographic (CT) scan revealed multiple lung tumors, multiple liver tumors, bulky
      retroperitoneal tumors with marked elevation of serum lactic dehydrogenase (LDH),
      alpha-fetoprotein, and beta subunit of human chorionic gonadotropin (HCG-beta).
      The patient was referred to our hospital for treatment. Scrotal ultrasonography
      and physical examination revealed bilateral normal testes. Because of bulky
      retroperitoneal masses with elevated specific tumor markers as well as bilateral
      normal testes, our diagnosis led to extra-gonadal germ cell tumor. Because the
      pulmonary lesion had increased rapidly, chemotherapy was performed without the
      tumor biopsy. After multiple chemotherapy regimens including BEP (bleomycin,
      etoposide, cisplatin), high-dose chemotherapy, and TIN (paclitaxel, ifosfamide,
      nedaplatin), all tumor marker levels fell into within the normal range. The tumor
      size was decreased remarkably on CT. Then, retroperitoneal lymphadenectomy were
      performed to confirm whether they still contained viable tumor cells. They
      contained only necrotic tissues without viable cancer cells by pathological
      examination. Consequently, the patient has been free of recurrence for 18 months
      after intensive treatment.

PMID- 16972632
TI  - [Testicular tumor following orchiopexy: a case report].
AB  - A 36-year-old male with history of left orchiopexy at age 11 received medical
      examination at the emergency department of our hospital with a left painful
      inguinal tumor as the chief complaint. A surgeon examined and suspected a femoral
      hernia. However, he noticed the patient having a tumor in the left scrotum as
      well, and referred the patient to our department. Alpha-fetoprotein was within
      the normal range, but beta-human chorionic gonadotropin and lactate dehydrogenase
      were slightly elevated. We diagnosed the case as a left testicular tumor and
      performed left high orchiectomy. On histopathological examination, the tumor was
      a seminoma and the left inguinal tumor was a lymph node metastasis (3 x 4 x 5
      cm). After operation, the tumor markers became normal and radiographic
      examination showed no evidence of metastasis to the retroperitoneal lymph nodes
      and to other organs. Subsequently, the patient was given 2 courses of systemic
      chemotherapy (bleomycin, etoposide, cisplatin) as an adjuvant therapy. At
      present, eleven months after operation, he showed no evidence of recurrence. To
      the best of our knowledge, there are 47 reported cases of this disease including
      ours in Japan.

PMID- 16972633
TI  - [A case of Kallmann syndrome: usefulness of the aging male's symptoms rating
      scale for assessment of subjective symptoms].
AB  - We report a case of Kallmann syndrome in which the aging male's symptoms rating
      scale (AMS) was useful for assessment of subjective symptoms. A 30-year-old male
      was admitted to Tsukuba University Hospital with a complaint of delayed puberty
      in May 2003. He presented with hypogonadism, gynecomastia and anosmia. The plasma
      levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and
      testosterone were very low. However, the LH-releasing hormone test and human
      chorionic gonadotropin (hCG) loading test identified normal function of pituitary
      and Leydig cell. After 12 months of treatment with hCG and human menopausal
      gonadotropin (hMG), the amount of pubic hair and the volume of testes had
      increased as well as the level of serum testosterone. The total score of AMS
      after treatment has been improved from 39 to 20 as compared with that before
      treatment.

PMID- 16972634
TI  - [Giant condyloma with malignant degeneration: a case report].
AB  - We report a case of giant condyloma with malignant degeneration. A 56-year-old
      male was referred to our hospital due to a penile infection that was resistant to
      antibiotic therapy for more than a year. The swelling appeared to be a penile
      cancer. We suspected malignancy and performed penile biopsies twice; however, the
      histopathological diagnosis was condyloma acuminatum and malignant findings were
      absent. We continued the antibiotic therapy for 3 months; however, no improvement
      was achieved. Therefore, total penectomy and urinary diversion were performed.
      The pathological diagnosis of the resected tissues was not only condyloma but
      also squamous cell carcinoma, and cancer cells appeared on the cut surface of the
      specimens. We added radiation therapy. There was no evidence of recurrence or
      metastasis at 18 months after surgery.

PMID- 16972635
TI  - Method for inducing the growth of new arteries in the myocardium.
AB  - OBJECTIVE: The creation of new coronary arteries has long been an objective of
      cardiac research. I describe a method for creating new blood vessels in the
      myocardium of the left ventricular wall in animals. METHODS: The myocardium was
      pierced by a fistula. Then a biodegradable hydrogel fiber with antithrombogenic
      and nonadhesive properties was inserted into the fistula with a venous catheter.
      Nine dogs were used. Three fibers were inserted in each heart, and two additional
      punctures were made and left empty as controls. RESULTS: During absorption of the
      fiber, the luminal surface of the fistula became lined with endothelial cells and
      developed many openings to capillary blood vessels of the myocardium naturally.
      Three straight fibers were inserted so they intersected in the myocardium. They
      created a new branched vessel. The fistulas had connections to original coronary
      arteries and worked as new arteries to supply blood to the area where they were
      created. CONCLUSIONS: It was possible to create new blood vessels in the
      myocardium in animals.

PMID- 16972636
TI  - Mucinous carcinoma identified as lung metastasis from an early rectal cancer with
      submucosal invasion by immunohistochemical detection of villin.
AB  - We encountered a male patient aged 64 with pulmonary mucinous carcinoma in whom a
      diagnosis of pulmonary metastasis from early rectal cancer with submucosal
      invasion was made based on an immunohistochemical examination. A rectal cancer
      was detected together with a mass in the lung. The mass in the lung was
      consistent with mucinous adenocarcinoma, whereas the invasion of rectal cancer
      was confined to the submucosa; thus, distant metastases appeared unlikely. These
      lesions were assessed using immunohistochemical staining for cytokeratin and
      thyroid transcription factor-1, which failed to make a definite diagnosis. A
      further assessment was made by staining for villin. Both neoplasms were positive
      for this protein, demonstrating a common brush-border pattern. A lung metastasis
      from rectal cancer with submucosal invasion was diagnosed. Villin is considered
      useful for detecting primary neoplastic lesions based not only on its specificity
      but also on its staining pattern, which is different from that of other proteins.

PMID- 16972637
TI  - Giant right atrial myxoma associated with tricuspid regurgitation.
AB  - A 55-year-old woman presented with dyspnea on effort for half a year that had
      progressed with time. Echocardiography showed a giant spherical mass (6 cm
      diameter) in the right atrium occupying almost the entire space of the atrium.
      The mass was attached to the interatrial septum with a wide base. There was
      moderate to severe tricuspid regurgitation. Emergency operation was performed via
      median sternotomy. Under cardiopulmonary bypass, the tumor was excised with the
      interatrial septum where the tumor was arising. The defect was closed using an
      autologous pericardial patch. Tricuspid annuloplasty was carried out with no
      residual tricuspid regurgitation.

PMID- 16972638
TI  - Successful mitral valve repair for active infective endocarditis accompanied by
      anorexia nervosa.
AB  - Infective endocarditis of the mitral area accompanied by anorexia nervosa is
      extremely rare. A 34-year-old Japanese woman presented with high fever and a
      heart murmur that had developed over the previous 2-month period.
      Echocardiography revealed mitral regurgitation and vegetation attached to the
      anterior mitral leaflet, which had markedly prolapsed to the left atrium. We
      removed the vegetation with a small part of the anterior mitral leaflet and
      successfully repaired the mitral valve. The patient showed good recovery, and the
      mitral regurgitation and left ventricular chamber size had satisfactorily
      decreased at 2 months after the operation.

PMID- 16972639
TI  - Wide resection of the upper right hemithorax combined with amputation of the
      right arm for a recurrent desmoid tumor.
AB  - A 66-year-old woman had a recurrent desmoid tumor in the right thoracic apex. The
      tumor infiltrated the brachial plexus and eventually rendered the upper right
      extremity functionless. The tumor was removed by aggressive wide resection of the
      right upper hemithorax with simultaneous amputation of the functionless right
      arm. Reconstruction of the chest wall was accomplished, utilizing the soft
      tissues of the remnant arm as a pedicled flap to cover the full-thickness defect.
      Aggressive wide resection of the chest wall with limb amputation is technically
      challenging but unavoidable in some cases of recurrent desmoid tumor.

PMID- 16972640
TI  - Consecutive left lower sleeve lobectomy and left S3 segmentectomy for a patient
      with node-negative double lung cancer.
AB  - A 74-year-old-man visited our hospital because of a dry cough. A chest radiograph
      showed a nodular shadow measuring 2.0 cm diameter in the left S3 segment and a
      tumor shadow measuring 3.5 cm diameter in the left S6 segment; no mediastinal
      lymph node enlargement was observed. The bronchoscopic findings revealed direct
      invasion of the tumor into the spur of the left B6 branch, but no abnormal
      findings were found in the upper bronchus. An endobronchial biopsy revealed
      squamous cell carcinoma in a left B6 biopsy specimen and adenocarcinoma in the
      left S3 lung biopsy specimen. The patient's lung function was not good, and an
      arterial blood gas analysis was Po2 69.3mmHg and PCO2 48.5 mmHg. We performed
      left lower sleeve lobectomy and left S3 segmentectomy simultaneously. He was
      discharged uneventfully on the 14th day after the operation, and he has since
      been doing fine without lung caner recurrence for 3 years after surgery.

PMID- 16972641
TI  - Bronchoplasty for bronchial carcinoid tumor without removing lung parenchyma.
AB  - A 15-year-old boy was admitted with a pneumothorax of the left lung. Computed
      tomographic scans demonstrated a tumor 20 mm in diameter situated on the left
      main to upper lobar bronchus that eventually was proved to be a typical carcinoid
      tumor by transbronchial biopsy. We performed bronchial resection with atypical
      bronchoplasty, which preserves lung parenchyma in cases of s-T1N0M0 disease. The
      patient has had no evidence of recurrence 7 years after surgery.

PMID- 16972642
TI  - Intraoperative infusion of epoprostenol sodium for patients with heparin-induced
      thrombocytopenia undergoing cardiac surgery.
AB  - Prevention of catastrophic thromboembolic complications during surgery in
      patients with heparin-induced thrombocytopenia (HIT) remains a challenging
      problem during cardiac surgery. We infused an increasing dose of epoprostenol
      sodium, which is one of three anti-HIT regimens available in Japan, ahead of
      administration of heparin and performed a mitral valve operation for a patient
      with type II HIT. The absence of thromboembolic events and platelet consumption
      during cardiopulmonary bypass, together with considerable reduction of platelet
      adhesion to the fibers of the membrane oxygenator, support the efficacy and
      safety of our strategy.

PMID- 16972643
TI  - Pulmonary suture abscess with false-positive 18F-fluorodeoxyglucose positron
      emission scan mimicking lung cancer recurrence.
AB  - We present the case of a 57-year-old woman with pulmonary suture abscess. She had
      undergone right S3 segmentectomy for early lung adenocarcinoma 7 years before and
      right breast-conserving surgery for invasive ductal carcinoma 5 months
      previously, followed by irradiation plus endocrine therapy. Chest radiography and
      computed tomography revealed an irregular mass (3.5 cm in diameter) between the
      residual S1 segment and the middle lobe, neighboring the staple line of the
      segmentectomy. 18F-fluorodeoxyglucose uptake into the mass increased, seen by
      positron emission scans. Therefore, we could not rule out the possibility of
      local recurrence of lung cancer and resected it. Pathologically and
      microbiologically, the mass was a suture abscess arising around the nylon suture
      of the previous segmentectomy. This lesion was the result of a foreign-body
      reaction, as confirmed by polarized microscopy. Moreover, titanium staples at the
      segmentectomy and breast-conserving surgery may also have contributed to this
      condition.

PMID- 16972644
TI  - Pulmonary lymphangioleiomyomatosis.
AB  - We report a case of lymphangioleiomyomatosis (LAM) in a 33-year-old woman. Left
      pneumothorax was noted during a physical checkup at a local clinic. Multiple
      bullae in the bilateral lungs were also seen on chest computed tomography.
      Therefore, she underwent surgery for diagnosis and therapy. A large number of
      cysts of various sizes were seen in the left pleural cavity, and a cyst located
      at the lingular region was resected. Histopathological examination of the cyst
      walls showed a thin rim of abnormal muscle consisting of spindle-shaped cells
      resembling smooth muscle cells as well as thick, eccentric, or concentric
      proliferation. The examination described above confirmed the diagnosis of LAM.
      The patient is currently being followed up on an outpatient basis.

PMID- 16972645
TI  - Pneumothorax after pneumonectomy: surgery with successful double lobe
      ventilation.
AB  - Contralateral pneumothorax is potentially lethal in patients who have undergone
      pneumonectomy. There are few reports about the diagnosis and treatment of this
      situation. This is a report of our experience with selective lobar ventilation of
      the middle and lower lobes using a guidewire and a bronchial blocker in the right
      upper bronchus of a patient who had previously undergone left pneumonectomy.

PMID- 16972646
TI  - Thoracic and cardiovascular surgery in Japan during 2004.

PMID- 16972647
TI  - [Side effects of antiglaucoma eye drops].

PMID- 16972648
TI  - [Repetitive instillation of 0.1% cyclosporin A eye drops induces miosis and
      anterior chamber inflammation-like reactions in monkey eyes].
AB  - PURPOSE: Miosis and anterior chamber inflammation-like reactions were recognized
      after six instillations of 0.1% cyclosporin A eye drops every 30 minutes into
      rabbit conjunctival sacs. In order to consider species specificity, 0.1%
      cyclosporin A eye drops were applied by the same method in monkeys. METHODS: Eye
      drops were applied in five monkeys (monkey A, B, C, D, E); in one eye as control
      and in nine eyes with 0.1% cyclosporin A. We investigated the changes of pupil
      diameter, intraocular pressure, and anterior chamber flare before and after
      applying the eye drops. We also examined the effect on ocular tissue
      histopathologically. RESULTS: Miosis was recognized in six eyes, but no
      significant intraocular pressure change was observed in any eyes. In both eyes of
      monkey A anterior chamber flare increased significantly, and flare increased
      slightly in both eyes of monkeys B, C, and D. On the other hand, there was no
      change in either eye of monkey E, including the control eye. Localized necrosis
      of nonpigmented ciliary epithelium was recognized at the beginning of the ciliary
      process in both eyes of monkey A. Mild cystoid degeneration of nonpigmented
      ciliary epithelium was seen at the beginning of the ciliary process in the right
      eye of monkey C, and in the left eye of monkey D. CONCLUSION: No species
      specificity can be recognized in monkeys from the fact that there is the
      selective destruction of nonpigmented epithelium at the beginning of the ciliary
      process after repeated instillation of 0.1% cyclosporin A eye drops, although
      there was a difference in miosis and anterior chamber inflammation-like reaction
      in individual monkeys.

PMID- 16972649
TI  - [Adverse reaction after use of latanoprost in Japanese glaucoma patients].
AB  - PURPOSE: Although latanoprost has proven to have a strong hypotensive effect,
      some patients show adverse reactions such as eyelid pigmentation, iridial
      pigmentation, or hypertrichosis. We prospectively investigated these adverse
      reactions. SUBJECTS AND METHODS: One hundred and one Japanese glaucoma or ocular
      hypertension patients were included. Iridial, eyelid, and eyelash photographs
      were taken before and at 6 months after latanoprost treatment. Increased eyelid
      pigmentation, iridial pigmentation, eyelash pigmentation, vellus hair of the lid,
      and hypertrichosis were assessed from these photographs. The correlation between
      the incidence of these adverse reactions and the time of instillation, type of
      glaucoma, sex, age, or concomitantly used eye drops, and the overlap of these
      were evaluated. RESULTS: Increased pigmentation of the eyelid was found in 6
      cases(5.9%), of the iris in 32 cases (31.7%), of the eyelashes in 29 cases
      (28.7%), vellus hair of the lid in 38 cases(37.6%), and hypertrichosis in 51
      cases(50.5%). Pigmentation of the eyelid was more frequently observed in patients
      who used latanoprost concomitantly (16.7%) than in those who did not use anti
      glaucomatous eye drops before latanoprost treatment (1.6%), or in those treated
      with latanoprost who had switched from other anti-glaucomatous eye drops (6.3%)
      (p= 0.03). CONCLUSIONS: The incidence of adverse reactions caused by latanoprost
      was higher in the eyelashes and iris than in the eyelid.

PMID- 16972650
TI  - [A clinical study of intraocular malignant lymphoma].
AB  - PURPOSE: We investigated whether vitreous cytology and the measurement of
      intravitreous cytokine were useful for the diagnosis of intraocular malignant
      lymphoma. SUBJECTS AND METHODS: 8 eyes of 5 patients with suspected intraocular
      malignant lymphoma during the past 15 months. 3 vitreous samples were collected
      from 3 patients at the time of pars plana vitrectomy. Polymerase chain
      reaction(PCR) amplification and flowcytometric analysis(FACS) of the vitreous
      samples were performed. Interleukin (IL)-10 and IL-6 concentrations were
      measured. RESULTS: Vitreous cytology showed increased atypical B lymphocytes. The
      vitreous IL-10/IL-6 ratio was higher than 1 in all cases. Monoclonal
      rearrangement of the immunoglobulin heavy chain gene and the light chain
      restriction of immunoglobulin were detected. CONCLUSION: The detection of the
      monoclonality of infiltrated cells into the vitreous by PCR amplification and
      FACS, and the measurements of IL-10 and IL-6 concentrations in the vitreous fluid
      may be useful in the diagnosis of intraocular malignant lymphoma.

PMID- 16972651
TI  - [Low penetrance of His26Asp mutation in the optineurin gene in a Japanese family
      with normal-tension glaucoma].
AB  - PURPOSE: Three glaucoma genes have been identified in open-angle glaucoma(OAG).
      In this study, two of these genes were analyzed in Japanese patients with OAG.
      SUBJECTS AND METHODS: After informed consent was obtained, the myocilin gene and
      the optineurin gene were analyzed in 99 Japanese patients with OAG, including 49
      cases of primary open-angle glaucoma(POAG) and 50 cases of normal-tension
      glaucoma(NTG). The patients were outpatients at the Tokyo Metropolitan Police
      Hospital. Family members were examined for the genes and clinical features if the
      proband had a mutation. RESULTS: One of the 99 patients had His26Asp mutation in
      the optineurin gene. None of the 240 subjects serving as controls had this
      mutation. The proband was a 37-year-old man diagnosed as having NTG. His father
      had the same mutation, but had normal clinical findings. His mother did not have
      the mutation, but had ocular hypertension. Polymorphism of Thr34Thr was observed
      in a wild type for the proband, and heterozygous change was found in his parents.
      For the myocilin gene, only the Asp208Glu mutation was found in his mother.
      CONCLUSION: His26Asp mutation in the optineurin gene showed low penetrance in a
      Japanese family with NTG.

PMID- 16972652
TI  - [A case of anterior ischemic optic neuropathy associated with Vogt-Koyanagi
      Harada disease].
AB  - BACKGROUND: Although optic disc swelling is one of the common findings of Vogt
      Koyanagi-Harada (VKH) disease, severe visual field loss from optic disc
      involvement is not common. We report a case of severe visual field contraction
      from optic disc involvement in VKH disease. CASE REPORT: A 51-year-old woman was
      diagnosed as having VKH disease and was treated with intravenous pulse
      methylprednisolone. Exudative retinal detachments disappeared and visual acuity
      improved, but optic disc swelling was persistent in both eyes. Ten weeks after
      VKH disease onset, she claimed acute visual field loss in the right eye. Marked
      optic disc swelling with peripapillary hemorrhages and severe visual field loss
      were observed in the right eye. Fluorescein angiography showed filling delay and
      late leakage of the optic disc in the right eye. One month later, right optic
      disc swelling disappeared, but visual field loss remained. In addition, 5.5
      months later, the left optic disc swelled further, and the left visual field was
      markedly contracted. Hyperbaric oxygen therapy was added. The swelling in the
      left optic disc gradually decreased and disappeared in one month, but the visual
      field loss remained. CONCLUSIONS: The optic disc involvement with irreversible
      visual field loss in this case is thought to be due to anterior ischemic optic
      neuropathy, which may be a possible complication of VKH disease.

PMID- 16972653
TI  - [External quality assessment of drug susceptibility testing for Mycobacterium
      tuberculosis].
AB  - OBJECTIVE: The Committee for Mycobacterial Examinations has planned and
      implemented the third external quality assessment of drug susceptibility testing
      for Mycobacterium tuberculosis to the hospital and private laboratories. METHOD:
      The Committee delivered 20 M. tuberculosis strains, exactly pairs of 10 strains,
      which were evaluated and standardized for the drug resistance pattern in the WHO/
      IUATLD supra-national laboratory network (SRLN). The agreement of the majority of
      SRLN laboratories was considered as the gold standard of susceptibility result
      for each strain tested. Each laboratory performed the drug susceptibility testing
      (DST) with its own routine method. The sensitivity to detect drug resistance, the
      specificity for susceptible strain, the efficiency of overall agreement, the
      reproducibility for each pair, and kappa coefficient were calculated to evaluate
      their performance. DST was performed for isoniazid (INH), rifampicin (RFP),
      streptomycin (SM) and ethambutol (EB). RESULTS: A total of 48 results has been
      collected. The overall sensitivity, specificity, efficiency, reproducibility and
      kappa coefficient for each anti-tuberculosis drug tested were as follows
      respectively; 100%, 99.0% (62.5-100), 99.6% (85.0-100), 99.6% (90-100) and 0.991
      for INH; 97.7% (83.3-100), 100%, 98.6% (90-100), 99.0% (90-100) and 0.972 for
      RFP; 87.5% (66.7-100), 99.0% (87.5-100), 92.1% (80-100), 97.5% (70-100) and 0.84
      for SM; 99.5% (75.0-100), 97.9% (75.0-100), 98.5% (85.0-100), 97.9% (70-100) and
      0.97 for EB. Regarding private laboratories, all indicators showed 100% for INH
      but 2 hospital laboratories showed less than 90% in sensitivity. As for RFP, one
      private laboratory (4.3%) and 3 hospital laboratories showed less than 90% in
      sensitivity. The major difference between private and hospital laboratories was
      seen in EB. One hospital laboratory (4.0%) showed less than 90% in sensitivity
      and three (12.0%) showed less than 90% in specificity, compared to none in
      private laboratories. Additionally, six hospital laboratories (24.0%) showed less
      than 90% in reproducibility. As for quality improvement, two private laboratories
      that showed poor performance in 2003 have improved their quality up to 100% in
      2004. DISCUSSION: The overall efficiency by private and hospital laboratories
      satisfied WHO criteria. However, it diverged in each category of laboratories and
      hospital laboratories tended to show poor performance compared to the private
      ones. The reason for the difference was not clear, but the routine workload,
      allocated time and cost for the panel testing might contribute to it. The
      sensitivity of SM was relatively low compared to the other drugs as it was
      observed in 2003. It was mainly due to two strains to which the participating
      laboratories showed poor agreement to the gold standard. The difference of
      critical drug concentration for SM in Lowenstein-Jensen and in 1% Ogawa medium
      might contribute to the discrepancies. As for quality improvement, two private
      laboratories with poor performance in 2003 have shown marked improvement after on
      site evaluation. The results indicated the usefulness of external quality
      assessment for the maintenance and improvement of the quality of the test.

PMID- 16972654
TI  - [Number of sputum cultures by MGIT system needed to diagnose pulmonary
      tuberculosis].
AB  - PURPOSE: To study the number of sputum cultures by MGIT system (Becton-Dickinson)
      needed to diagnose pulmonary tuberculosis. OBJECT AND METHOD: Prospective study
      of all patients who visited our hospital, and were strongly suspected of
      pulmonary tuberculosis during the period from Jan. 2002 to Sept. 2003. In these
      patients, 3 consecutive sputum cultures were done by both MGIT-system and egg
      based Ogawa medium (1 slant). RESULTS: Altogether 290 cases of sputum-culture
      positive pulmonary tuberculosis were available for analysis. In 210 first-sputum
      smear positive cases, incremental yield of 3rd sputum culture in 3 consecutive
      MGIT cultures was equal to or less than 1.0% and 98.1% of culture positive cases
      were detected by 2 consecutive MGIT cultures. In 80 first-sputum-smear negative
      cases, incremental yield of 3rd sputum culture in 3 consecutive MGIT cultures was
      equal to or more than 5.0%, and 90.0% of culture positive cases were detected by
      2 consecutive MGIT cultures. This detection rate was almost the same as the
      calculated detection rate (91.4%) by 3 consecutive Ogawa (2 slant) cultures
      (previous standard method). CONCLUSION: It was suggested that 2 consecutive
      sputum cultures by MGIT were sufficient to detect M. tuberculosis in first-sputum
      smear positive cases, but 3 consecutive sputum cultures by MGIT were relatively
      useful in first-sputum-smear negative cases.

PMID- 16972655
TI  - [A case of endobronchial lesion due to infection with Mycobacterium
      intracellulare].
AB  - A 53-year-old man was hospitalized in April 2001 because of left cervical
      lymphadenopathy and a mass shadow in the left lingular segment. Bronchoscopy
      revealed an elevated lesion in the left main bronchus, but a biopsy showed no
      specific findings. A left cervical lymph node biopsy revealed lymphoid
      hyperplasia only and no malignancy. After the patient was discharged, bronchial
      irrigation solution from the left lingular segment was found to be positive for
      Mycobacterium intracellulare. In July 2001 the shadow in the left lingular
      segment had worsened, and bronchoscopy was performed again. This revealed
      ulceration in the left main bronchus and edematous narrowing of the bronchial
      lumen at the opening of the lingular segment. A granulated lesion accompained by
      severe inflammation was seen in a biopsied specimen taken from the same site.
      Bronchial lesion induced by an acid-fast-stain positive nontuberculosis
      mycobacteria was noted. Treatment with rifampicin (RFP), clarithromycin (CAM),
      ethambutol (EB), and streptomycin (SM) was started, but a rash most likely caused
      by RFP developed, and RFP was replaced by ciprofloxacin (CPFX). The treatment was
      continued and symptoms improved. Since non-tuberculous mycobacteriosis
      accompanied with bronchial lesions is rare, a case report was made.

PMID- 16972656
TI  - [A case of pulmonary Mycobacterium fortuitum infection successfully treated with
      Kampo treatments].
AB  - A 72-year-old male was referred to our hospital in August 2001 for his pulmonary
      M. fortuitum infection. His symptoms were coughing, pyrexia, hemoptysis, general
      malaise, and insomnia. He had been suffering from these symptoms since 1982,
      though the intensive anti-mycobacterial chemotherapy such as three-drug (RFP, SM,
      and INH), twice two-drug (KM and SM and cycloserine and enviomycin) and four-drug
      (CAM, EB, RFP, and KM) regimens were administered for 26 months from July 1999.
      His symptoms tentatively improved after chemotherapy, but soon recurred with
      smear positive sputum. We decided to withdraw all antibacterial agents to treat
      him with decoction of Ninjinyoueito according to the diagnostics Kampo medical
      science in September 2001. After this prescription, his subjective symptoms
      gradually improved, and ten months later his sputum converted to smear negative.
      Because of recurrence of his general malaise in August 2002, we replaced the
      Ninjinyoueito by Seishoekkito, based on the Kampo diagnostics. His physical
      conditions remained good until 2005. In addition, the sputum smear examination
      maintain the level below +/-. We evaluate that Kampo (Chinese traditional
      medicine) treatment resulted in favorable response. Though it is not common to
      prescribe Kampo-medicine for intractable infectious diseases, we believe that
      Kampo-medicine is effective in some cases associated with host defense
      mechanisms.

PMID- 16972657
TI  - [Transient worsening of chest radiograph and development of lymphadenopathy
      during chemotherapy for miliary tuberculosis].
AB  - A-37-year old woman was referred to our hospital because of bilateral pulmonary
      micronodular shadows on chest X-ray. Prednisolone was reported to be administered
      for her coughs and dyspnea more than a month, but was discontinued recently.
      Under the diagnosis as miliary tuberculosis, we started to treat her with the
      combined use of pyrazinamide, isoniazid, rifampicin, and ethambutol. Then her
      symptoms subsided gradually. Two months later, however, high fever developed,
      followed by exacerbation of the radiographic shadows, and marked cervical and
      mediastinal lymphadenopathy. We considered them so-called paradoxical worsening,
      and continued the antituberculosis therapy unchanged. Those clinical
      manifestations began to subside about 4 months after the initiation of the
      treatment. Paradoxical worsening has been described as a relatively rare
      manifestation, and seem to be attributable to prompt recovery of the immunity to
      mycobacterial antigens after the use of antituberculous therapy. We considered
      that, in this case, disseminated tuberculosis and firstly administered steroid
      that might suppress immune function, and discontinuation of steroid therapy
      followed by the bactericidal antituberculous chemotherapy were associated with
      the development of the paradoxical reactions, by analogy with immune
      reconstitution syndrome frequently reported in HIV-related tuberculosis patients.

PMID- 16972658
TI  - [A case of pulmonary Mycobacterium shimoidei infection].
AB  - A 68 year-old male who was ex-smoker presented with fever and cough. Chest
      radiograph showed infiltrative shadows in both upper lung fields. A sputum smear
      for acid-fast bacilli was positive. But the isolate was not identified by
      polymerase chain reaction method. Acid-fast bacilli were cultured from sputum,
      but the identification was not done by DNA-DNA hybridization method.
      Mycobacterium shimoidei was identified by 16S ribosomal RNA sequencing with
      98.42% matching. Rifampicin, ethambutol, clarithromycin, pyrazinamide, and
      ciprofloxacin were administered, and the symptom and abnormal shadows on chest
      radiography improved. And three months later from the initiation of treatment,
      sputum smear for acid-fast bacilli became negative. Chest CT scan four months
      after treatments showed decrease of infiltrative shadows. We had treated him for
      six months, and after that no recurrence occurred.

PMID- 16972659
TI  - [Clinical manifestation of Q fever and tuberculosis, similarly caused by
      intracellular parasites].
AB  - Q fever is a generic term for pneumonia, bronchitis, etc. caused by infection
      with Coxiella burnetii, a rickettsia-related species of bacteria, in humans. Q
      fever is a transient and acute febrile illness that takes a course similar to
      influenza, and its clinical picture greatly differs from that of tuberculosis
      that takes a chronic course. The reason for this is thought to be because the
      generation time of C. burnetii is extremely short (several tens of minutes)
      compared with Mycobacterium tuberculosis, though those are similar intracellular
      parasites. Q fever is fourth- or fifth-ranked among the community-acquired
      pneumonias in the United States and Europe but has a good prognosis with 1-2% of
      mortality even in the cases that follow a natural course without treatment.
      Meanwhile, there is a chronic type that follows a protracted course or has a poor
      prognosis. Therefore, cases definitely diagnosed with Q fever or strongly
      suspected of Q fever should seek aggressive treatment. Q fever is definitely
      diagnosed by confirming significant increase in serum antibody titer, but the
      patients should be followed because in many cases it takes a long time before
      serum antibody titer increases. Beta-lactams are ineffective against C. burnetii,
      an obligate intracellular parasite. Although tetracyclines, macrolides,
      quinolones, rifampicin, etc. are used effectively in the treatment of Q fever,
      many cases appear to improve by beta-lactam administration because the illness
      often takes a natural course.

PMID- 16972660
TI  - [Age-related changes in bone structure using peripheral quantitative computed
      tomography].

PMID- 16972661
TI  - [Degenerative disorders of the skeleton in elderly].
AB  - Skeletal degeneration such as osteoporosis and osteoarthritis increases morbidity
      and mortality of aged persons. It is associated with inflammation induced by
      micro particles from bone and cartilage matrices and reduction in bone quality
      that could be due to disturbance of regulatory function of bone mass and
      structure in response to mechanical loading. Deformity in the skeletons induced
      by osteoporosis and osteoarthritis is irreversible and accumulating. To establish
      the substantial methods to alleviate it, we need to know the effects of gonad
      hormone deficiency underlying in the diseases.

PMID- 16972662
TI  - [Pathology of bone diseases in elderly subjects].
AB  - In elderly persons, structural changes occur in bone tissue. The bone histology
      and histomorphometry demonstrate that the trabecular volume and thickness are
      reduced and trabecular connection is disrupted in cancellous bone, and that the
      cortical layer becomes thinner and the bone lacuna is enlarged in compact bone.
      These features become more serious in osteoporotic patients. Even weak forces can
      cause fragility fractures in osteoporotic patients. However, a prolonged period
      is not always required for fracture healing in elderly patients. Elderly persons
      can suffer from many disorders, such as osteomalacia, bone diseases associated
      with joint diseases and bone tumors.

PMID- 16972663
TI  - [Age-related transformation of bone metabolism].
AB  - Bone mass reaches peak bone mass by the age of about from eighteen to twenty in
      men and women, since then it is reduced with aging every year. Decrease in bone
      mass with aging is classified postmenopausal osteoporosis and senile osteoporosis
      of involutional osteoporosis. Bone mass is reduced suddenly in menopausal period
      on postmenopausal osteoporosis, but it is reduced slowly in men and women on
      senile osteoporosis. We will give an outline of age-related transformation of
      bone metabolism classified from growth period to maturity period, menopausal
      period in men and women, and aging period.

PMID- 16972664
TI  - [Socio-economics on care for the elderly patients with hip fracture].
AB  - We conducted research on elderly patients with hip fracture. It started with
      investigating relationship between the length of stay (LOS) and walking ability
      as the chosen indicator for outcome. We then used extended LOS that included days
      at transferred hospitals, and also conducted cost performance analysis. Thirdly,
      procedure and schedule were compared among UK, US, and Japan. We found positive
      relationship between LOS and walking ability. LOS required to gain final walking
      ability was shorter when a single hospital completed procedure. Japan had more
      than 3 times longer LOS than the other two countries, due to more variety of
      procedure and longer interval between steps. New guideline on treatment process
      is awaited, and outcome-based measurement should be included in calculating
      reimbursement.

PMID- 16972665
TI  - [Pathogenesis of fracture will be important in the research work of
      osteoporosis].
AB  - Osteoporosis is characterized by compromised bone strength, and the increased
      susceptibility to fractures that impair patient's quality of life and increase
      mortality constitutes a national burden in the aging society. The pathogenesis of
      osteoporosis has been recently astringent on estrogen deficiency that induces
      secondary metabolic changes such as calcium imbalance. Thus, the main research
      issue in osteoporosis has been turning to the mechanical basis of bone fractures.
      According to the definition of osteoporosis proposed by National Institutes of
      Health, bone strength reflects the integration of two components: the bone mass
      (bone mineral density) and bone quality. Of the two, bone mineral density (BMD)
      is known to be the major determinant of future fracture risk. In contrast, bone
      quality assessment has not been applied to clinical practice except for the
      measurement of bone turnover markers. The present paper reviewed the bone quality
      concepts and discussed the future potential research propositions.

PMID- 16972666
TI  - [Provision for fragility of bone and its risk factors].
AB  - Fractures in osteoporosis patients have been affected by not only low bone
      density but also many factors like bone quality, shape of bone, soft part tissue,
      nutrition, ability of exercise, fall etc.. There are a lot of risk factors in
      fragility of osteoporotic bone. As for some factors, there is impossible of
      improvement like a genetic factor, but there are some factors like nutrition,
      exercise, environment which can improve the fragility of bones in osteoporotic
      patients. Provision for fragility of bone is improvement for each risk factor.

PMID- 16972667
TI  - [Clinical sign--height loss and vertebral deformity].
AB  - Loss of height may be an important clinical sign of vertebral deformation and/or
      fracture in postmenopausal women and elderly men. The presence of at least one
      spine fracture will lead to about a 2 cm decrease in height. Guidelines in the
      U.S. say that height loss greater than 1.5 inches or more from the maximum height
      among asymptomatic women may be associated with osteoporotic vertebral
      compression fractures. In Japan, the prevalence of spine deformation starts to
      increase among individuals in their early 70's, as does the prevalence of those
      with spine deformation at two or more vertebrae. It has been reported that not
      only individuals with clinical spine fracture but those with spine deformation
      show diminished activity of daily living (ADL) and quality of life (QOL) and also
      high mortality. Spine fracture should be suspected among individuals whose
      stature has decreased even if they manifest no symptoms.

PMID- 16972668
TI  - [DXA, QUS, and radiogram].
AB  - In this article, an outline of dual energy X-ray absorptiometry (DXA),
      quantitative ultrasound (QUS), and radiogram, and their characteristics,
      problems, and assessment of osteoporosis in the elderly were reviewed. It is well
      known that both DXA and QUS are available to risk assessment of fractures.
      However, because lumbar bone mineral density (BMD) is overestimated in the
      elderly complicated with fracture, deformity, and osteosclerotic change in the
      lumbar vertebra (e), some cases are unsuitable to measurement of BMD with lumbar
      DXA. To define vertebral fracture, visual semiquantitative and morphometric
      methods are used. In addition, differential diagnosis of osteoporotic vertebral
      fractures is necessary. Thus, to establish an exact diagnosis of osteoporosis in
      the elderly, it is important to understand some problems associated with the
      elderly.

PMID- 16972669
TI  - [Micro-CT, clinical CT].
AB  - Osteoporosis is a systemic skeletal disease characterized by bone fragility and
      susceptibility to fracture risk. Bone fragility and fracture risk primarily
      reflect the integration of bone density and bone quality. Micro-computed
      tomography (CT) and clinical CT are useful techniques for assessing osteoporosis
      and predicting fracture risk. Micro-CT is useful for assessing 3D trabecular bone
      structure. Quantitative CT (QCT) and peripheral QCT (pQCT) are promising tools
      for the measurements of the bone density. CT-based finite element method (FEM)
      may provide some useful information about bone mechanics and predict bone
      strength and fracture site. The usefulness and the limitations of these
      techniques are reviewed in this paper.

PMID- 16972670
TI  - [Metabolic markers of bone--post-guideline].
AB  - Metabolic markers of bone are common clinical parameters for the evaluation of
      the pathophysiologic conditions and efficacy of the treatment, although they are
      not helpful for differential diagnosis of osteoporosis. The guideline published
      officially is helpful for practitioners and non-experts in the field. The
      distributions of urinary NTX and bone specific alkaline phosphatase are
      essentially same between primary osteoporotic postmenopausal women less than 70
      years old and those over 70 years. No differences were found in the other
      metabolic markers between these groups. Although clinical evidence for patients
      over 85 years old is not enough, we do not have to think of age in the clinical
      application of metabolic markers of bone, if renal functions are within normal
      ranges.

PMID- 16972671
TI  - [Medical treatment of osteoporosis].
AB  - Osteoporosis is a skeletal disease characterized by increased risk of fracture
      due to reduced bone strength. Osteoporosis-associated fractures not only impair
      patients' quality of life (QOL) but also diminishes life expectancy. The most
      important goal in the treatment of osteoporosis is fracture prevention. To
      achieve this goal, in addition to lifestyle changes including balanced diet,
      increased exercise and fall prevention, most high-risk patients need
      pharmacological intervention. Based on the currently available evidence, the
      first-line medications are bisphosphonates and raloxifene. Active vitamin D alone
      may not be efficacious enough but may particularly be important in Japan as a
      surrogate for vitamin D and calcium supplementation. A new bone anabolic therapy
      by parathyroid hormone (PTH), which is already in clinical use in other
      countries, is also expected to become available in Japan in the near future.

PMID- 16972672
TI  - [Active vitamin D and vitamin K as therapeutic agents for osteoporosis].
AB  - Active vitamin D has been most widely used in Japan for the treatment of
      osteoporosis. However, clinical evidence for its efficacy as an anti-osteoporotic
      drug is scarce in terms of fracture prevention. Recent reports suggest that
      active vitamin D may prevent fracture not only through enhancement of intestinal
      calcium absorption but also by improving bone quality and/or strength
      independently of bone mass and by improving neuromuscular function to reduce the
      number of fall. Low serum concentrations of vitamin K have been reported in
      patients with osteoporosis, and serum osteocalcin appears to be undercarboxylated
      in these individuals, a process dependent on vitamin K. Undercarboxylated
      osteocalcin is also a significant risk for hip fracture. Clinical studies in
      Japan suggest that menatetrenone (vitamin K2) reduces skeletal losses and, in a
      small randomized clinical trial, it reduced the rate of vertebral fractures.
      Menatetrenone is currently used in Japan, the Republic of Korea and Thailand.

PMID- 16972673
TI  - [SERM].
AB  - SERM is the abbreviation of the selective estrogen receptor modulator which is
      the synthetic ligands of estrogen receptor (ER) acting estrogenically or anti
      estrogenically among various tissues through modifying the ER function.
      Clomifene, tamoxifen, toremifene and raloxifene are generally classified as SERM
      in the clinical use. The main cause of postmenopausal osteoporosis is estrogen
      deficiency and it was revealed that the continuous combined use of conjugated
      estrogen and medroxyprogesterone acetate reduced the relative risk of femoral
      neck fracture to 0.66, however increased the relative risk of cardiovascular
      event and breast cancer to 1.29 or 1.26, respectively. From the standpoint of
      safe and clinical compliance for the breast and uterine tissue, raloxifene is
      recommendable for middle aged postmenopausal osteoporosis.

PMID- 16972674
TI  - [Effects of bisphosphonate for quality and strength of bone].
AB  - Bisphosphonate prevents the fracture by controlling the function of osteoclasts
      and inhibiting bone absorption powerfully for osteoporosis. It is shown
      clinically that both alendronate and risedronate reduce postmenopausal
      osteoporosis patient's vertebral and nonvertebral fractures. Recently it became
      clear that bisphosphonate not only reduces bone absorption, but also improves
      bone quality such as bone microarchitecture and material properties. Furthermore,
      we showed using finite element analysis that internal use of bisphosphonate
      reduces strain of the cancellous bone inside vertebral body within one year, and
      notably decreases the region of high strain which is easy to break. Internal use
      of bisphosphonate improves the bone density distribution inside vertebral body,
      and strengthens the structure of load support of the spine. The structural
      improvement of spine leads to prevention of fracture.

PMID- 16972675
TI  - [Adequate treatment with bisphosphonates for senile osteoporosis].
AB  - The characteristics of senile osteoporosis are as follows. (1) Bone turnover is
      not always decrease in senile osteoporosis. (2) Senile patients have urgent
      fracture risk, such as aging, prevalent fracture(s), low bone mass, and
      increasing bone turnover. (3) Most of patients are insufficient of calcium and
      vitamin D. The important things of the treatment for senile osteoporosis with
      bisphosphonates are (1) to take calcium and vitamin D sufficiently to avoid the
      excess secretion of parathyroid hormone, (2) to pay attention gastro-esophageal
      reflux disease, especially the patients with spinal deformity, and (3) to adhere
      the patient with treatment.

PMID- 16972676
TI  - [Evaluation of therapeutic intervention on bone mass and turnover through
      monitoring of biochemical markers of bone turnover].
AB  - Monitoring of biochemical markers of bone turnover has brought about a number of
      breakthroughs in the area of osteoporosis management. Of these, the following
      three are of particular interest: 1) monitoring of these biochemical markers
      represents the only clinical means available for assessment of bone quality: 2)
      it helps grasp the patient's condition, as well as predicts the patient's risk
      for developing fractures: and 3) it allows the effect of therapeutic intervention
      to be evaluated at an earlier stage than bone mineral density. Thus, monitoring
      of these biochemical markers not only helps strengthen motivation among
      healthcare professionals for osteoporosis treatment, but also helps enhance
      patient compliance to treatment.

PMID- 16972677
TI  - [Surgical treatment for osteoporotic spinal fractures in the thoraco-lumbar
      spine].
AB  - Most of osteoporotic spinal fractures can be successfully treated with
      conservative treatment. In some patients, however, conservative treatment is not
      effective and progressive vertebral collapse with neurological problems at
      thoraco-lumbar spine may occur. In this chapter, surgical indication and timing
      in patients with osteoporotic vertebral collapse are described. Surgical options
      including vertebroplasty, kyphoplasty, anterior reconstruction, posterior
      reconstruction, and combined anterior and posterior surgery are also described.
      The readers can understand both advantages and disadvantages of each surgical
      procedure. In senile patients, preoperative general conditions including comorbid
      medical problems should be taken into account to determine surgical treatments.
      Rigid and long spinal fusion using metal implants may lead to spinal fractures at
      adjacent vertebral bodies to the fused segments.

PMID- 16972678
TI  - [Surgical treatment for proximal femoral fracture in osteoporosis].
AB  - Proximal femoral fracture is one of the common fractures in osteoporosis, and the
      incidence of it is rising. Early restoration of the patient's preinjury activity
      level is the primary goal in the treatment of proximal femoral fractures in the
      elderly to avoid complications. Surgery should be carried out as soon as is
      practicable. Proximal femoral fracture is classified into femoral neck fracture
      (intracapsular fracture) and trochanteric fracture (extracapsular fracture). The
      standard of care for undisplaced femoral neck fracture is primarily internal
      fixation, and hemiarthroplasty for displaced neck fracture in elderly patients.
      Internal fixation is indicated for trochanteric fractures.

PMID- 16972679
TI  - [Nutritional care and management for osteoporosis].
AB  - A significant point of nutritional care and management for osteoporosis is that
      calcium and vitamin D are recommended to be actively administered on top of
      sufficient intake of energy and the other nutrients including protein. Daily
      intake of calcium and vitamin D is encouraged at least 800 mg and 10 to 20
      microg, respectively. Calcium and vitamin D are also important for maximizing the
      effect of osteoporosis drug therapy. Supplement of calcium or vitamin D could be
      a supportive measure, when their necessary amount is difficult to be consumed.

PMID- 16972680
TI  - [Exercise for fall prevention and osteoporosis treatment].
AB  - The recent meta-analyses of many randomized controlled trials that examined the
      effectiveness of exercise on the fall frequency and the bone mineral density were
      reviewed. All of the various exercise programs showed the significant reduction
      of the number of falls. In addition, the bone mineral density also increased with
      aerobics, resistance training, and walking in the lumbar spine and increased with
      walking in the femoral neck. Although exercise programs have not yet showed
      evidence for fracture prevention, it seemed to reduce the risk of fall and
      osteoporosis.

PMID- 16972681
TI  - [The optimal therapeutic intervention for osteoporosis from the socioeconomic
      perspectives].
AB  - Osteoporosis is too often underestimated regarding its true burden to the
      society. Hip fracture is associated with high mortality and morbidity. It both
      increases the medical expenditure and additional cost associated with long-term
      care. Although its significance is not widely recognized, vertebral fracture
      increases further fracture risk, and is also associated with compromised QOL. In
      order to establish a therapeutic guideline based on socioeconomic perspectives,
      analyses are mandatory based on simulation models such as Markov model. To
      determine the optimal therapeutic intervention for osteoporosis from the
      socioeconomic perspectives, studies on collecting such data as the epidemiology
      of fracture and the fracture prevention efficacy of each drug are required.

PMID- 16972682
TI  - [Metabolic bone diseases in patients with diabetes mellitus].
AB  - Both of genetic backgrounds and life-style are involved in pathogenesis of
      diabetes mellitus and osteoporosis. Nowadays they are common diseases in the
      elderly people in the developed countries. Quality of life in people who have
      diabetes and osteoporosis are frequently impaired. Thus, adequate care and
      treatment are needed for both diseases. Bone metabolism is regulated by
      complicated mechanisms that involve mineral metabolism and endocrine systems.
      Recent studies have shown that sympathetic nerve system, glucose and lipid
      metabolism are also involved in bone remodeling. Clinical studies have
      demonstrated that diabetes is an independent risk factor for fracture in the
      elderly women. Therefore, one should understand and care for disorders in bone
      metabolism in patients with diabetes individually, since pathophysiology of
      diabetes is complicated and diverse in each patient.

PMID- 16972683
TI  - [Chronic kidney disease-mineral and bone disorder (CKD-MBD)].
AB  - Changes in mineral and bone metabolism are prevalent in chronic kidney disease.
      There are several types of renal bone disease, called 'renal osteodystrophy
      (ROD)'. ROD includes osteitis fibrosa, osteomalacia, adynamic bone disorder, and
      mixed osteodystrophy. Osteitis fibrosa is high turnover bone due to secondary
      hyperparathyroidism. Osteomalacia is low turnover bone concomitant of increased
      osteoid. Adynamic bone disorder is low turnover bone due to excessive suppression
      of the parathyroid glands and recently represents the major bone lesion in
      dialysis patients. More recently, the term 'Chronic Kidney Disease-Mineral and
      Bone Disorder(CKD-MBD)' was proposed to describe the clinical syndrome that
      develops as a systemic disorder of mineral and bone metabolism due to chronic
      kidney disease such as vascular calcification.

PMID- 16972684
TI  - [Nutrition-related bone disease].
AB  - Bone disorders clearly related to nutrition are osteomalacia and osteoporosis.
      Osteomalacia is caused by a deficiency of vitamin D or a disturbance of its
      metabolism. Dietary deficiency of phosphate or excess of aluminum or cadmium will
      also cause osteomalacia. Osteoporosis is associated with low intake of calcium
      and other nutrients. Dietary copper deficiency might stimulate bone metabolism
      and increase in hip fractures. Excess vitamin A intake was also associated with
      lower bone mineral density and higher risk of hip fractures. Excess vitamin D
      sometimes causes mental simplicity, congenital heart disease and calcification of
      soft tissue. Therefore not only diet but also drugs and supplements of nutrients
      should be carefully observed in older women.

PMID- 16972685
TI  - [Bone disease related to rheumatoid arthritis].
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by
      progressive bone destruction, in which proinflammatory cytokines such as tumor
      necrosis factor-alpha play essential roles. Recent studies have revealed an
      important involvement of osteoclasts in bone destruction of RA. In this review, I
      would like to explain the molecular mechanism of osteoclast development in RA,
      and propose the possibility of anti-osteoclast therapy to the disease.

PMID- 16972686
TI  - [Primary hyperparathyroidism].
AB  - Primary hyperparathyroidism is the most frequent cause of hypercalcemia in
      ambulatory patients. Elevated serum parathyroid hormone in the presence of
      persistent hypercalcemia is the diagnostic sine qua non for primary
      hyperthyroidism. Since examination of serum calcium became a routine diagnostic
      test, most patients with primary hyperparathyroidism are asymptomatic at the time
      of diagnosis. Primary hyperparathyroidism in most of patients is caused by
      parathyroid adenoma, and parathyroid hyperplasia and cancer are rare causes of
      the disorder. Parathyroidectomy is the primary treatment of choice for primary
      hyperparathyroidism by any cause. Parathyroidectomy should be performed in most
      of patients with primary hyperparathyroidism, but asymptomatic or only mildly
      hypercalcemic patients are treated according to the guidelines for surgical
      treatment established by the NIH Consensus Development Conference in 2002. For
      patients with osteoporosis who are not indicated for or decline surgical
      procedures can be treated with bisphosphonates.

PMID- 16972687
TI  - [Paget's disease of bone].
AB  - Paget's disease of bone (PDB) is a chronic disorder characterized by focal
      abnormalities of bone turnover. The symptoms of PDB include bone pain, bone
      deformity, osteoarthritis, and an increase in risk of pathological fracture and
      neurological problems. PDB is the second most common metabolic bone disease in
      European countries, although PDB is uncommon in Japan. PDB shows geographical and
      ethnic clustering. Based on this, two hypotheses of etiology of PDB have been
      proposed. One hypothesis is that PDB results from a slow virus infection of
      osteoclasts with paramyxovirus. The other is that PDB is a genetic disease. The
      development of bisphosphonate has brought major changes to the treatment of PDB.
      In Japan, etidronate and calcitonin are approved by the Ministry of Health,
      Labour and Welfare for treating PDB. Risedronate is under development for
      treating PDB in Japan.

PMID- 16972688
TI  - [Diagnostic imaging of skeletal metastases].
AB  - Skeletal metastases are the most frequent in malignant bone tumor. Vast majority
      of skeletal metastases are encountered in middle-aged to elderly persons.
      Skeletal metastases should be included in differential diagnosis of bone lesion
      in elderly persons. In this mini-review, clinical features are mainly discussed
      and some recent advances are also described. They are 1) mechanisms of skeletal
      metastasis, 2) vicious cycle (what happens in the process of osseous metastasis
      progression), 3) frequency, site and number of skeletal metastases, 4) osseous
      response to metastatic tumor, 5) diagnostic imaging of skeletal metastasis, 6)
      bone metabolic markers in osseous metastasis, and 7) complications.

PMID- 16972689
TI  - [Bone and joint infection].
AB  - Older adults are at risk for the immune dysfunction associated with advanced age,
      which contribute to their increased risk of infection. Hematogenous osteomyelitis
      occurs not only in children, but also in older adults. Iatrogenic septic
      arthritis can be occured after the intraarticular injection for the
      osteoarthritis in aging society. Tuberculous spondylitis occurs in older adults
      and the differential diagnosis with pyogenic spondylitis and vertebral metastasis
      is important.

PMID- 16972690
TI  - [Early detection of pancreatic cancer by novel proteomic technique].
AB  - Pancreatic cancer is the fifth leading cause of cancer-related mortality in
      Japan. Early detection in pancreatic cancer is one of the most feasible
      strategies to improve outcome. We compared plasma proteome between pancreatic
      cancer patients and healthy controls using surface-enhanced laser
      desorption/ionization coupled with hybrid quadrupole time-of-flight mass
      spectrometry. Proteomic spectra were generated from a total of 245 plasma samples
      obtained from two institutes. A discriminating proteomic pattern was built from
      training cohort using machine learning algorithm and was applied two validation
      cohorts. This set discriminating cancer patients in the first validation cohort
      with a sensitivity of 90.9% and a specificity of 91.9%, and was further validated
      in an independent cohort at a second institution. When combined with CA19-9, 100%
      tumor of pancreatic cancers, including early stage tumors, were detected. In this
      report, we describe a possible detection of early pancreatic cancer using novel
      proteomic technique.

PMID- 16972691
TI  - Suicide trends and geographical variations in the United Kingdom, 1991-2004.
AB  - Almost 6,000 people killed themselves in the UK in 2004. While suicide rates in
      the UK fell between 1991 and 2004 this decrease did not occur in all areas. Large
      disparities remain between suicide rates in the countries of the UK, and between
      regions and local areas. This article also presents inequalities in suicide rates
      by deprivation, and considers change over time, for men and women, and for
      different age groups.

PMID- 16972692
TI  - Trends in deaths related to drug misuse in England and Wales, 1993-2004.
AB  - In this article we report trends in deaths related to drug misuse in England and
      Wales from 1993 to 2004, looking particularly at the period between 1999 and
      2004, for which there was a Government target to reduce these deaths by 20 per
      cent. Although there was an overall decline in deaths related to drug misuse
      between 1999 and 2004, the percentage reduction, at 9 per cent, was less than the
      Government target. There was an increase in deaths between 2003 and 2004, largely
      accounted for by deaths involving heroin/methadone and morphine. Mortality rates
      were highest in young adults and an increase in mortality rates within this group
      appears to have been the driver behind rising mortality trends during the 1990s.

PMID- 16972693
TI  - Measuring deprivation in England and Wales using 2001 Carstairs scores.
AB  - Carstairs scores, first calculated in the 1980s based on data from the 1981
      Census, were designed as a summary measure of relative deprivation within small
      populations. They were based on four indicators from the census which were
      considered to represent material disadvantage, and have since been widely used to
      examine the relationship between deprivation and health. This article describes
      how Carstairs scores were calculated for England and Wales based on data from the
      2001 Census and also presents the resulting geographical patterns of deprivation.

PMID- 16972694
TI  - Trends in premature mortality in England and Wales, 1950-2004.
AB  - Premature mortality is a major public health concern but there has been little
      consensus among researchers on how it should be defined and reported. In this
      article four means of measuring early deaths are considered using four different
      age thresholds to define prematurity. Using these four indicators, trends in
      premature mortality are reported for England and Wales from 1950 to 2004. All
      measures show that, however 'premature' is defined, levels of premature mortality
      have decreased markedly over time. This article discusses which mortality
      indicator and age threshold would be most appropriate for a measure of premature
      mortality for use in national mortality statistics for England and Wales.

PMID- 16972695
TI  - Estimating residents and staff in communal establishments from the 2001 Census.
AB  - Censuses of population in the UK provide the only comprehensive source of data on
      the population resident in communal establishments. Accurate information on the
      population resident in institutions and, in particular, counts of those living in
      medical and care establishments, is important for a range of social policy issues
      and for local service planning and resource allocation. This article identifies
      issues in distinguishing residents from staff when using the 2001 Census communal
      establishment data in England and Wales. Possible options to improve the
      reliability of institutional population estimates for analysis and reporting are
      evaluated against quality and credibility criteria and the impact of each
      adjustment option assessed. The article concludes with a recommendation on what
      users can do when using 2001 Census outputs at both the aggregate level (e.g.
      area-based figures) and the individual level (e.g. the sample of anonymised
      records).

PMID- 16972696
TI  - Infant and perinatal mortality 2004 and 2005: health areas, England and Wales.

PMID- 16972697
TI  - Unexplained deaths in infancy, 2005.

PMID- 16972698
TI  - Death registrations in England and Wales, 2005: area of residence.

PMID- 16972699
TI  - Mortality statistics 2004: injury and poisoning.

PMID- 16972700
TI  - Adaptive designs: expectations are high.

PMID- 16972701
TI  - Application of adaptive designs--a review.
AB  - A literature search has been performed to review applications of the adaptive
      design methodology based on the combination test or conditional error function
      approach. Some features of the 60 papers identified are summarized, e.g., the
      specific methodology used, calendar year, country, impact factor of the journal,
      number of planned and performed stages respectively, stopping for futility
      boundaries, type of adaptations and others. A selection of the ten recent
      publications in journals with the highest impact factors is discussed in more
      detail. Most applications up to now aim at sample size reassessment, the majority
      of papers is coming from Germany. Although we found that renowned journals allow
      for sufficient space to present the new statistical methodology in all its
      necessary details, the general impression is that the presentation of the
      adaptive designs methodology in applied papers has to be improved. Education and
      development of standards could help to achieve this.

PMID- 16972702
TI  - An overview of statistical approaches for adaptive designs and design
      modifications.
AB  - With adaptive design methods for clinical trials, design elements such as sample
      size or further interim sample sizes may be changed during the course of the
      trial depending on all previously collected data. The focus of the overview is on
      group sequential approaches where the types of adaptations need not be specified
      in advance. An overview of the different statistical approaches for adaptive
      design methods proposed in the literature is given, relations between these
      methods are described and some perspectives of application and for future
      research are discussed.

PMID- 16972703
TI  - Flexible designs by adaptive plans of generalized Pocock- and O'Brien-Fleming
      type and by self-designing clinical trials.
AB  - Flexible designs are provided by adaptive planning of sample sizes as well as by
      introducing the weighted inverse normal combining method and the generalized
      inverse chi-square combining method in the context of conducting trials
      consecutively step by step. These general combining methods allow quite different
      weighting of sequential study parts, also in a completely adaptive way, based on
      full information from unblinded data in previously performed stages. So, in
      reviewing some basic developments of flexible designing, we consider a
      generalizing approach to group sequentially performed clinical trials of Pocock
      type, of O'Brien-Fleming-type, and of Self-designing-type. A clinical trial may
      be originally planned either to show non-inferiority or superiority. The proposed
      flexible designs, however, allow in each interim analysis to change the planning
      from showing non-inferiority to showing superiority and vice versa. Several
      examples of clinical trials with normal and binary outcomes are worked out in
      detail. We demonstrate the practicable performance of the discussed approaches,
      confirmed in an extensive simulation study. Our flexible designing is a useful
      tool, provided that a priori information about parameters involved in the trial
      is not available or subject to uncertainty.

PMID- 16972704
TI  - Sample size recalculation in internal pilot study designs: a review.
AB  - The adequacy of sample size is important to clinical trials. In the planning
      phase of a trial, however, the investigators are often quite uncertain about the
      sizes of parameters which are needed for sample size calculations. A solution to
      this problem is mid-course recalculation of the sample size during the ongoing
      trial. In internal pilot study designs, nuisance parameters are estimated on the
      basis of interim data and the sample size is adjusted accordingly. This review
      attempts to give an overview on the available methods. It is written not only for
      biometricians who are already familar with the the topic and wish to update their
      knowledge but also for users new to the subject.

PMID- 16972705
TI  - Some aspects of the application of internal pilot studies.
AB  - This is a discussion of the paper' Sample size recalculation in internal pilot
      study designs' by Tim Friede and Meinhard Kieser, appearing in this special issue
      on adaptive designs.

PMID- 16972706
TI  - FDA's critical path initiative: a perspective on contributions of biostatistics.
AB  - This article describes the motivation for, description of, and the objectives and
      plans for the FDA's initiative that was introduced in March of 2004 by way of a
      report titled 'Innovation or Stagnation?--Challenge and Opportunity on the
      Critical Path to New Medical Products'. The FDA initiative is very much an
      outreach effort and a wake-up call to many constituencies to contribute and
      partner to improve the product development process and thereby to contribute to
      the success rate of new products that will benefit the public. We discuss in
      general terms where some of the opportunities and challenges exist for the
      discipline of biostatistics to make contributions to this effort over the next
      few years. In particular, guidance development in five areas is considered as is
      the need to devote new energy and efforts to quantitative risk assessment and
      safety evaluation, an area that has lagged the attention received in the efficacy
      evaluation area.

PMID- 16972707
TI  - A regulatory view on adaptive/flexible clinical trial design.
AB  - Recently there is growing interest in use of adaptive or flexible designs for
      development of pharmaceutical products. Statistical methodology has been greatly
      advanced in the literature. However, there are still some important issues with
      the methodology and application. In addition, there are many other challenges
      with these designs, including efficiency of these designs in the entire
      development program, trial conduct and logistics, the infrastructure of an
      adaptive trial, the regulatory evaluation of trial results and trial conduct,
      etc. Up till now, regulatory experience in these designs is very limited. We
      share some of the challenges.

PMID- 16972708
TI  - Confirmatory clinical trials with an adaptive design.
AB  - Adaptive designs are one of the most promising developments in statistics with
      applications to clinical trials. Obviously, knowledge at the beginning of a
      clinical trial will always be limited. Thus it may seem logical that the
      knowledge from accumulating information should be used to optimize the design of
      the trial. This paper discusses conditions under which this may be possible in
      phase III clinical trials where the principal aim is confirmation of hypotheses
      that have been developed in earlier stages of drug development.

PMID- 16972709
TI  - Adaptive designs from the viewpoint of an academic biostatistician.
AB  - This is a discussion of the following three papers appearing in this special
      issue on adaptive designs: 'FDA's critical path initiative: A perspective on
      contributions of biostatistics' by Robert T. O'Neill, 'A regulatory view on
      adaptive/flexible clinical trial design' by H. M. James Hung, Robert T. O'Neill,
      Sue-Jane Wang and John Lawrence; and 'Confirmatory clinical trials with an
      adaptive design' by Armin Koch.

PMID- 16972710
TI  - Challenges in implementing adaptive designs: comments on the viewpoints expressed
      by regulatory statisticians.
AB  - This is a discussion of the following three papers appearing in this special
      issue on adaptive designs: 'FDA's critical path initiative: A perspective on
      contributions of biostatistics' by Robert T. O'Neill; 'A regulatory view on
      adaptive/flexible clinical trial design' by H. M. James Hung, Robert T. O'Neill,
      Sue-Jane Wang and John Lawrence; and 'Confirmatory clinical trials with an
      adaptive design' by Armin Koch.

PMID- 16972711
TI  - Opening the adaptive toolbox.
AB  - This is a discussion of the following three papers appearing in this special
      issue on adaptive designs: 'A regulatory view on adaptive/flexible clinical trial
      design' by H. M. James Hung, Robert T. O'Neill, Sue-Jane Wang and John Lawrence;
      'Confirmatory clinical trials with an adaptive design' by Armin Koch; and 'FDA's
      critical path initiative: A perspective on contributions of biostatistics' by
      Robert T. O'Neill.

PMID- 16972712
TI  - A consultant's perspective on the regulatory hurdles to adaptive trials.
AB  - This is a discussion of the following two papers appearing in this special issue
      on adaptive designs: 'A regulatory view on adaptive/flexible clinical trial
      design' by H. M. James Hung, Robert T. O'Neill, Sue-Jane Wang and John Lawrence
      and 'Confirmatory clinical trials with an adaptive design' by Armin Koch.

PMID- 16972713
TI  - Methodological developments vs. regulatory requirements.
AB  - This is a discussion of the following three papers appearing in this special
      issue on adaptive designs: 'FDA's critical path initiative: A perspective on
      contributions of biostatistics' by Robert T. O'Neill, 'A regulatory view on
      adaptive/flexible clinical trial design' by H. M. James Hung, Robert T. O'Neill,
      Sue-Jane Wang and John Lawrence; and 'Confirmatory clinical trials with an
      adaptive design' by Armin Koch.

PMID- 16972714
TI  - Confirmatory seamless phase II/III clinical trials with hypotheses selection at
      interim: general concepts.
AB  - Traditional drug development consists of a sequence of independent trials
      organized in different phases. Full development typically involves (i) a learning
      phase II trial and (ii) one or two confirmatory phase III trial(s). For example,
      in the phase II trials several doses of the new compound might be compared to a
      control and/or placebo with the goal of deciding whether to stop or continue
      development and, in the latter case, selecting one or two "best" doses to carry
      forward into the confirmatory phase. The phase III trials are then conducted as
      stand-alone confirmatory studies, not incorporating in their statistical analyses
      data collected in the previous phases. Seamless phase II/III designs are aimed at
      interweaving the two phases of full development by combining them into one
      single, uninterrupted study conducted in two stages. In the dose-finding example
      above, one (or more) dose(s) are selected after the first stage based on the
      available data at interim, and are then observed further in the second stage. The
      final analysis of the selected dose(s) includes patients from both stages and is
      performed such that the overall type I error rate is controlled at a prespecified
      level regardless of the dose selection rule used at interim. The adequacy of the
      dose selection at interim is obviously a critical step for the success of a
      seamless phase II/III trial. In this paper we focus on the description of
      flexible test procedures allowing for adaptively selecting hypotheses at interim
      and thus allowing the combination of learning and confirming in a single seamless
      trial. We review the statistical background, introduce different test procedures
      and compare them in a power study. In a subsequent paper (Schmidli et al., 2006)
      we give several applications from our daily practice and discuss related
      implementation issues in conducting adaptive seamless designs.

PMID- 16972715
TI  - Confirmatory seamless phase II/III clinical trials with hypotheses selection at
      interim: applications and practical considerations.
AB  - Adaptive seamless phase II/III designs combine a phase II and a phase III study
      into one single confirmatory clinical trial. Several examples of such designs are
      presented, where the primary endpoint is binary, time-to-event or continuous. The
      interim adaptations considered include the selection of treatments and the
      selection of hypotheses related to a pre-specified subgroup of patients.
      Practical aspects concerning the planning and implementation of adaptive seamless
      confirmatory studies are also discussed.

PMID- 16972716
TI  - How practical are adaptive designs likely to be for confirmatory trials?
AB  - This is a discussion of the following papers appearing in this special issue on
      adaptive designs: 'Confirmatory Seamless Phase II/III Clinical trials with
      Hypotheses Selection at Interim: General Concepts' by Frank Bretz, Heinz
      Schmidli, Franz Konig, Amy Racine and Willi Maurer; and 'Confirmatory Seamless
      Phase II/III Clinical Trials with Hypotheses Selection at Interim: Applications
      and Practical Considerations' by Heinz Schmidli, Frank Bretz, Amy Racine and
      Willi Maurer.

PMID- 16972717
TI  - Confirmatory seamless phase II/III clinical trials with hypotheses selection at
      interim: opportunities and limitations.
AB  - This is a discussion of the following two papers in this special issue on
      adaptive designs: 'Confirmatory seamless phase II/III clinical trials with
      hypotheses selection at interim: General concepts' by Frank Bretz, Heinz
      Schmidli, Franz Konig, Amy Racine and Willi Maurer, and 'Confirmatory seamless
      phase II/III clinical trials with hypotheses selection at interim: Applications
      and practical considerations' by Heinz Schmidli, Frank Bretz, Amy Racine and
      Willi Maurer.

PMID- 16972718
TI  - Plan to be flexible: a commentary on adaptive designs.
AB  - This is a discussion of the following three papers appearing in this special
      issue on adaptive designs: 'Nested repeated confidence intervals and switching
      between noninferiority and superiority' by Joachim Hartung and Guido Knapp;
      'Confirmatory Seamless Phase II/III Clinical trials with Hypotheses Selection at
      Interim: General Concepts' by Frank Bretz, Heinz Schmidli, Franz Konig, Amy
      Racine and Willi Maurer; and 'Confirmatory Seamless Phase Il/III Clinical Trials
      with Hypotheses Selection at Interim: Applications and Practical Considerations'
      by Heinz Schmidli, Frank Bretz, Amy Racine and Willi Maurer.

PMID- 16972719
TI  - An adaptive hierarchical test procedure for selecting safe and efficient
      treatments.
AB  - We consider the situation where during a multiple treatment (dose) control
      comparison high doses are truncated because of lack of safety and low doses are
      truncated because of lack of efficacy, e.g., by decisions of a data safety
      monitoring committee in multiple interim looks. We investigate the properties of
      a hierarchical test procedure for the efficacy outcome in the set of doses
      carried on until the end of the trial, starting with the highest selected dose
      group to be compared with the placebo at the full level alpha. Left truncation,
      i.e., dropping doses in a sequence starting with the lowest dose, does not
      inflate the type I error rate. It is shown that right truncation does not inflate
      the type I error if efficacy and toxicity are positively related and dose
      selection is based on monotone functions of the safety data. A positive relation
      is given e.g. in the case where the efficacy and toxicity data are normally
      distributed with a positive pairwise correlation. A positive relation also
      applies if the probability for an adverse event is increasing with a normally
      distributed efficacy outcome. The properties of such truncation procedures are
      investigated by simulations. There is a conflict between achieving a small number
      of unsafely treated patients and a high power to detect safe and efficient doses.
      We also investigated a procedure to increase power where a reallocation of the
      sample size to the truncated treatments and the control remaining at the
      following stages is performed.

PMID- 16972720
TI  - An adaptive two-stage design with treatment selection using the conditional error
      function approach.
AB  - As an approach to combining the phase II dose finding trial and phase III pivotal
      trials, we propose a two-stage adaptive design that selects the best among
      several treatments in the first stage and tests significance of the selected
      treatment in the second stage. The approach controls the type I error defined as
      the probability of selecting a treatment and claiming its significance when the
      selected treatment is indifferent from placebo, as considered in Bischoff and
      Miller (2005). Our approach uses the conditional error function and allows
      determining the conditional type I error function for the second stage based on
      information observed at the first stage in a similar way to that for an ordinary
      adaptive design without treatment selection. We examine properties such as
      expected sample size and stage-2 power of this design with a given type I error
      and a maximum stage-2 sample size under different hypothesis configurations. We
      also propose a method to find the optimal conditional error function of a simple
      parametric form to improve the performance of the design and have derived optimal
      designs under some hypothesis configurations. Application of this approach is
      illustrated by a hypothetical example.

PMID- 16972721
TI  - Combining treatment selection and definitive testing.
AB  - This is a discussion of the following two papers appearing in this special issue
      on adaptive designs: 'An adaptive hierarchical test procedure for selecting safe
      and efficient treatments' by Franz Konig, Peter Bauer and Werner Brannath, and
      'An adaptive two-stage design with treatment selection using the conditional
      error function approach' by Jixian Wang.

PMID- 16972722
TI  - Repeated confidence intervals in self-designing clinical trials and switching
      between noninferiority and superiority.
AB  - In self-designing clinical trials, repeated confidence intervals are derived for
      the parameter of interest where the results of the independent study stages are
      combined using the generalized inverse chi-square-method. The confidence
      intervals can be calculated at each interim analysis and always hold the
      predefined overall nominal confidence level. Moreover, the confidence intervals
      calculated during the course of the trial are nested in the sense that a
      calculated interval is completely contained in all the previously calculated
      intervals. During the course of the self-designing trial the sample sizes as well
      as the number of study stages can be determined simultaneously in a completely
      adaptive way. The adaptive procedure allows an early stop for significance. The
      clinical trial may be originally designed either to show noninferiority or
      superiority. However, in each interim analysis, it is possible to change the
      planning from showing superiority to showing noninferiority or vice versa. Since
      the repeated confidence intervals are nested, there is no risk to loose the
      noninferiority once showed when, after an interim analysis, the trial is
      continued in an attempt to reach superiority. A simulation study investigates the
      behavior of the considered confidence intervals. The performance of the derived
      nested repeated confidence intervals is also demonstrated in examples showing
      both kinds of switching during an ongoing trial.

PMID- 16972723
TI  - Adaptive vs. group sequential self-designing trials.
AB  - This is a discussion of the paper. 'Repeated Confidence Intervals in Self
      Designing Clinical Trials and Switching between Non-Inferiority and
      Superinferiority' by Joachim Hartung and Guido Knapp, appearing in this special
      issue on adaptive designs.

PMID- 16972724
TI  - Planning and analyzing adaptive group sequential survival trials.
AB  - The use of adaptive methods has experienced increasing interest in the current
      literature on group sequential designs. Group sequential analysis in survival
      trials usually apply the error spending function approach due to the
      unpredictable amount of information available in an interim analysis. An
      alternative way is to apply adaptive methods where additionally the maximum
      amount of information and other designing parameters can be changed based on the
      information available at the interim stage. In this paper, it is shown how the
      inverse normal method can be used within a survival design using the log-rank
      test for comparing two survival functions. This method allows for many kinds of
      design modifications. In case of no modifications, the inverse normal method
      coincides with the commonly used analysis strategy. It is straightforward to
      specify effect estimates. Confidence intervals for the hazard ratio that can be
      calculated at each stage of the trial and intervals that can only be computed by
      the end of the trial are proposed. The latter also enables the calculation of
      median unbiased estimates. Overall p-values can be defined analogously.
      Properties of the analyses techniques are investigated and compared with
      alternative approaches. It is shown that the proposed analysis technique might
      help to rescue an underpowered study and opens the way to other types of changes
      in design. The proposed technique is implemented in the software ADDPLAN Adaptive
      Design, Plans and Analyses (http://www.addplan.com).

PMID- 16972725
TI  - Survival endpoints and adaptive designs.
AB  - This is a discussion of the paper 'Planning and analyzing adaptive group
      sequential survival trials' by Gernot Wassmer, appearing in this special issue on
      adaptive designs.

PMID- 16972726
TI  - A brief review on software developments for group sequential and adaptive
      designs.
AB  - In this paper the currently available software we know for group sequential and
      adaptive designs is briefly reviewed. Stand-alone packages as well as modules
      within software packages or programming languages exist. New software
      developments for adaptive designs enable the user to perform data dependent
      design adaptations while controlling the Type I error rate.

PMID- 16972727
TI  - [The clinic history and the doctor-patient relationship].

PMID- 16972728
TI  - [Characteristics of patients admitted with enteral nutrition in a service of
      clinical medicine].
AB  - BACKGROUND: When a patient is unable to swallow enough calories by mouth and has
      his digestive tube working normally, the Enteral Nutrition (EN) is prescribed.
      Our aims was identify the patient who requires EN by sounding at Clinical Medical
      admission. METHODS: From 11/2001 to 11/ 2002; 331 patients were attended in
      common rooms. 50 of them (15%) required EN. Retrospective descriptive study was
      made, evaluating: demographic data, diagnoses, comorbilities, self-validity,
      staying, nosocomial complications, studies, medicaments, inter-consulting and
      mortality as well. RESULTS: In 50 patients under EN, 56 % were men, with an age
      rate of 65 years Standar Error (SE) 2.37 and daily life activity medium rate was
      2 (SE) 0.35. Diagnoses at admission: Strocke 22%, acute pneumonia of community
      22%, pneumonia by bronchoaspiration 10 %, acute confusional syndrome 10%, etc.
      Comorbilities: 54% presented 3 or more concurrent diseases, Hypertension 60 %,
      Dementia 28%, type 2 Diabetes and strocke 26%, iskemic cardiopathy 14%, etc.
      Admission time rate: 6 days (SE) 2.02, staying at intensive care unit 40%.
      Nosocomial complications came up in 34%, 76% ACS, 11.7% urinary tract infection,
      pneumonia and endovascular infection 1 each. 4 labs were required in rate (SE)
      1.14, and 3 complementary studies per patient (SE) of 0.24. In ambulatory
      treatment they used 3 drugs as an average (SE) 0.37. The highest prescription day
      approached 7 as average (SE) of 0.61. At discharge they left with an average of 4
      (SE) 0.39. In every case kinesiotherapy and phonoaudiology were used as well.
      Ther was interconsulting regarding infectology in 24%, general surgery 16%.
      Mortality 22%. CONCLUSION: EN is usual in clinical admission. It regards an
      elderly patient with lacking self-validity, who over 50% of cases presents more
      than three comorbilities (mostly hypertension). Facts of admission usually
      registered: neurological pathologies and infections. Admission length was the
      same as general settlers. Almost half of them needed intensive care assistance.
      Nosocomial complications are usually found. They are patients who require many
      drugs at home, while admitted and discharge time as well. In every one
      kinesiotherapy and phonoaudiology were applied. Mortality raised high. Unable
      chance to use commercial diets was not a trouble to feed them.

PMID- 16972729
TI  - [Hyperhomocystinemia as a thrombotic risk factor in patients suffering from
      systemic lupus erithematosus and antiphospholipid syndrome].
AB  - OBJECTIVES: to detect the prevalence of hyperhcy in SLE patients with and without
      antiphospholipid syndrom; to compare the Hcy levels between those patients and
      healthy controls and to determine the correlation between hyperhcy and
      antiphospholipid antibodies. PATIENTS AND METHODS: we studied 44 SLE patients: 17
      had antiphospholipid syndrom and 27 didn't have it, and we compared them to 24
      healthy controls. All of them where checked clinically and with laboratory tests
      like anticardiolypin antibodies, lupus anticoagulant and Hcy. Hcy > 9 was
      considered abnormal. Patient who had hyperhcy were treated with folic
      acid+vitB6+vitB12 a month along. STATISTICAL ANALYSIS: cualytative variables: chi
      square or Fischer's; cuantitative variables: Student's T test or Mann-Whitney's
      test. RESULTS AND CONCLUSIONS: there were 35 trombotic manifestations in 44
      patients. Hyperhcy was present in 27 SLE patients (61,4%), 12 of them had
      antiphospholipid syndrom. Hcy concentrations patients vs.controls was
      statisticaly different (p= 0,002). There was also stastisticaly different the hcy
      concentration from SLE patients with SAF vs controls (p=0,003) and without SAF vs
      controls (p= 0,015). From 33 SLE patients, 20 (33%) were aCL(+). 15(75%) of them
      had hiperhcy.

PMID- 16972730
TI  - [Treatment of hypertension in type 2 diabetes: importance of therapeutic
      selection].
AB  - BACKGROUND: Type 2 diabetes and essential hypertension are the most common causes
      of end-stage renal disease in Argentina. Over 887 organ transplantations
      performed in the year 2004, 577 were kidney transplants. In urban and rural
      populations hypertension was more prevalent in type 2 diabetics, in particular
      systolic hypertension. Outcome studies are used to measure clinically meaningful
      primary end points, such as mortality and cardiovascular morbidity. Our current
      knowledge of the effects of antihypertensive agents on cardiovascular risk in
      hypertensive patients with type 2 diabetes has been achieved from subgroups
      included in large-scale studies. SCOPE: The present study, based on a search of
      MEDLINE literature in the period 1990-2005, revised major randomised studies with
      the purpose of finding out which are the most advisable therapeutic strategies
      against this morbid association. The majority of patients require 2 to 4
      antihypertensive medications to achive BP levels that correlate with diminished
      progression of target organ damages. Despite the advantages of renin-angiotensin
      system inhibitors the initial choice of medications should be based on the
      evidences of target organ damages. In those patients without any evidence of
      complications, the primary goal seems to be achieving their BP to < 130/80 mm Hg
      beyond the differences among antihypertensive drugs classes, while in those with
      target organ damage evidences maintain BP < 120/75 mm Hg.

PMID- 16972731
TI  - [Cementless Spotorno stem. Long term results].
AB  - Spotorno stem is a tapered straight cementless stem; Spotorno stem achieved
      initial stability by wedging a proximal fluted, straight stem into a retained bed
      of femoral trabecular and cortical bone, rectangular cross section provides
      excellent rotational stability distally. The titanium-aluminum-niobium alloy
      enables the fast ongrowth of newly formed osseous tissue to act as secondary
      stabilization This retrospective study reviews 26 Spotorno stems, the mean follow
      up was 134 months. Clinical results were graded excellent and good in 93 per cent
      of hips. At follow-up, none patient presented radiological evidence of aseptic
      stem loosening and 100 per cent of stems showed stable fixation.

PMID- 16972732
TI  - [Epidemiology of rheumatic diseases: a study over the morbility prevalence].
AB  - The Rheumatic Diseases are a problems of public health than greater attention
      they require of the sanitary authorities of many countries. The absence in
      Cordoba Argentina, of investigations to know the magnitude of this problem, they
      motivated this work. The objective of this work it was to know the frequency with
      which these illnesses they are perceived for the population in Cordoba,
      Argentina. Was made a probabilistic sampling, with a size of sample of 429
      individuals, with a level of 95% confidence. It is concluded that the rheumatic
      affections constitute a suffering perceived for more than the half of the
      population over 20 years, with a predominance in the women. The osteoarthrosis is
      a most common condition the defined rheumatic disease, whereas in the group of
      the inespecifics rheumatic disorders the pain of neck was that of greater
      prevalence.

PMID- 16972733
TI  - [Detection of arterial hypertension in school childrens].
AB  - INTRODUCTION: Hypertension is a multifactorial desease, with increasingly
      incidence and prevalence, that is why it is considered a public health issue.
      OBJECTIVES: To know the prevalence of hypertension in children from 6 to 12 years
      old, in Cipolletti city. To check if there are differences as regards sex and
      age. To institutionalizalice blood pressure messurement as part of the rutinary
      physical examination in the control of a child. METHODS AND MATERIALS: This was a
      cross sectional study. Blood pressure readings were obteined from 1038 students
      aged between 6 and 12 years old; who belong to 7 public schools of Cipolletti.
      Mercury sphyngomanometer and cuffs of 7.5 per 15 cm and 12 per 22 cm were used.
      The auscultatory method was used in phase I and V of Korotkoff. The second Task
      Force recomendations for blood pressure in children were followed. Blood pressure
      readings were obteined in 3 visits. Those students who had blood pressure
      messurement iqual to or higher than those established for hypertension were
      identified during each visit: boys 115/75 mmHg (6-8 years) 118/79 mmHg (9-10
      years) and 122/80 mmHg (11-12 yars); girls 113/74 mmHg (6-8 years) 118/79 mmHg (9
      10 years) and 122/79 mmHg (11-12). RESULTS: The prevalence of hypertension is
      3.37%, being more frecuent in the range of ages that go from between 6 to 8
      years, which corresponds to a 74.29% of the hypertensed children. The hypertense
      group messurements of blood pressure are: a)Boys: 122.92 mmHg +/- 4.11/78.43mmHg
      +/- 5.19; b)Girls: 123.63 mmHg +/- 7.43/80.22mmHg +/- 2. There were not
      significant differences between sexs at the 5% (a=0.05) level. The blood pressure
      has never been messurered to 597 students (58%). CONCLUSIONS: The prevalence of
      hypertension in Cipolletti is similar to international statistics. There is a
      number of children with hypertension that is not detected during medical
      examination due to lack of blood pressure messurement institutionalization.

PMID- 16972734
TI  - [Bibliometric analysis of doctorate thesis on the health sciences area: first
      part, odontology].
AB  - OBJECTIVE: The purpose of the following study was to describe trends in the use
      of information by dentistry thesists and their research topics in Medical
      Education, Ethics and History. MATERIAL AND METHODS: Of a total of 290 doctorate
      thesis of the Dentistry Faculty made from 1965 to 2002, were identified: 3 theses
      on Medical Education and 1 on Ethics. On these, bibliographic quotations from
      periodic and non periodic publications, as well as quotations from doctorate
      thesis and congress acts were analyzed. In addition the antiquity of these was
      analyzed considering a period of five years between the date of accomplishment of
      the thesis and the one of the used bibliographical quotation. RESULTS: The total
      of analyzed quotations was of 492, presenting an average of 123 quotations per
      thesis. 62 per cent of the quotations corresponded to non periodic publications,
      37 per cent to periodic publications and 2 per cent to quotations from doctorate
      thesis and congress acts. In regard of the antiquity of the quotations, 42 per
      cent was smaller to 5 years and 58 per cent was greater than that period of time.
      CONCLUSION: We concluded the doctorate thesis represent the highest degree of
      scientific and academic expression, and constitute a rich and valuable source of
      data. The analysis of these theses is very important because it provides
      information about the trends and innovations on the on the areas of Medical
      Education, Ethics and History. It would be (very) useful to extend the
      bibliometric analysis towards other thematic areas, generating a reference for
      future research.

PMID- 16972735
TI  - [Cytokeratin 7 and 20 in Barrett's esophagus].
AB  - Barrett's esophagus (BE) has been identified as the most important risk factor
      for adenocarcinoma of the distal esophagus. BE has been categorized as long
      segment (LSBE) if it extends 3 cm or more up the esophagus and as short-segment
      (SSBE) if it extends less than 3 cm into esophagus. Intestinal metaplasia may
      also develop in gastric mucosa (IMG) at the gastroesophageal junction. IMG has a
      much lower risk to progress to dysplasia or carcinoma when compared with SLBE or
      SSBE. Moreover, these conditions are difficult to distinguish one from another
      only based on endoscopic and morphologic criteria. Therefore the aim this study
      was to evaluate the cytokeratin (CK) 7 and 20 inmunoreactivity patterns in these
      intestinal metaplasias with the purpose to determine the precise anatomic site of
      the biopsy. Biopsy specimens from 14 patients with LSBE, 6 with SSBE and 7
      patients with IMG were inmunohistochemically stained with monoclonal antibodies
      to CK 7 and 20. Barrett's CK7/20 pattern was characterized by superficial and
      deep CK7 reactivity and only superficial CK 20 staining in the intestinalized
      mucosa. This pattern was found in all 7 (100%) patients with LSBE, and was absent
      in all 7 patients with IMG. All biopsy specimens from patients with IMG showed no
      staining for CK7 and diffuse surface positivity for CK20. 67% of the biopsy
      specimens from patients with endoscopic SSBE showed Barrett's CK7/20 pattern, and
      the remaining 33% specimens showed the IMG staining pattern. Based on our data
      the inmunohistochemical determination of CK7/20 is an excelent tool with high
      specificity in distinguishing LSBE and SSBE from IMG.

PMID- 16972736
TI  - [An experience in the use of NTIC (New Technology for Information and
      Communication) in the teaching process of the immune system].
AB  - INTRODUCTION: Not very often an integrated approach is applied in knowledge areas
      as Immune System, instead, the contents are usually a sort of "atomization" that
      prevents from having a holistic vision of the set as a whole. At the moment, our
      university students usually incorporate the Internet in their study work,
      similarly, the teachers can resort to this tool to "widen" the boundaries of the
      real classes. Perhaps, to achieve a deeper study level in this knowledge field,
      the use of NTIC may result an appropriate resource for complementing and
      supporting the current conventional techniques. OBJECTIVE: To create a
      communication space designed to deepen and up-date knowledge as well as to help
      the student construct a comprehensive, significant structure of knowledge by
      making interrelations with concepts previously acquired. MATERIAL AND METHODS:
      Course supported in a digital platform Moodle like, in LEV, FCEF and N, UNC.
      http://routerlab.efn.uncor.edu/moodle Category: Natural Sciences.
      http://lev.efn.uncor.edu/course category.php)id=2 RESOURCES: Power Point files:
      "Immune System" and "Cytokines"; forum discussion: Contents selected and
      organized upon a constructivist approach aiming at a reflective student
      responsible for his own learning (self learning). RESULTS: The students according
      to their own concerns and time availability selected to deepen the knowledge
      field. The possibility to interact permanently in the discussion forum generated
      closer bonds between the participants, enriched the analysis about the different
      dealt issues, raised concerns that altogether brought about the rebuilding of the
      contents in a significant learning. CONCLUSIONS: Bearing in mind that the
      educational contents are vital, it also has been proved that the use of NTIC
      provides of tools for the distance education courses and of useful resources for
      the teaching-learning sciences.

PMID- 16972738
TI  - [Aging and gynecologic cancer].
AB  - The interrelation between cancer and ageing in women is emphasized, on its
      increased incidence, in their molecular background, into the particular
      biological characteristics of the different tumors and the effects of ageing in
      the affected women.

PMID- 16972739
TI  - [Breast cancer. current use of the extra-pleural exploration of the internal
      mammary chain].
AB  - The interest to know the Internal Mammary Chain (IMC) Involvement , is that it is
      a lymphatic filter as primary as the axilla. Anatomic-surgical fundaments, were
      presented for their exploration. Fifty (50) pectus-sternal, analizing the number
      of nodes (average 9,7 per specimen), located preferably in the three first
      intercostal spaces, were studied. In the second phase IMC with a staging
      criterion and extrapleural way, resecting 1 or 2 costal cartilages, were
      explored. In 78 patients, pathological-anatomy correlation between IMC and the
      axilla, we observed 6% positive IMC with negative axilla. More recently in the
      era of the setinel node, we have explored IMC in 44 patients through intercostal
      spaces and without cartilages resection. In 28 patients we performed through
      radioisotopic way and gamma probe and in the remaining 16, through anatomic
      search if the tumor was either upper mid or lower. The most frequent spaces
      explored were in the 2nd and 3rd; 2,27 nodes average per patient. The
      pathological-anatomy between IMC and the axilla revealed the following results:
      axilla (-) IM (-): 59%; axilla (+) MI (-): 25%; axilla (+) IM (+): 11% and axilla
      (-)IM (+): 5%. We concluded that this is a non-aggressive method, with an
      excellent tolerance that allows the evaluation of another filter as primary as
      the axilla and that together they represent the best systemic disease
      prognostics. We believe that its exploration is justified in those cases in which
      the histological result , correlated with the axilla, allows a therapeutic
      approach change.

PMID- 16972740
TI  - [Conservative management of the axillary nodes in operable breast cancer].
AB  - Over the years, the treatment of breast cancer has changed dramatically. We
      briefly describe those changes and also the different therapeutic approches to
      the axillary nodes. Over the last century, the primary goal was to avoid radical
      surgery of the breast. However, during the last decades, the interest was mainly
      focused on the possibility of treating the axila in a conservative way, in an
      effort to minimize the adverse effects of linfadenectomy. The sentinel node
      technique is of key importance, because nowadays it is possible to diagnose
      breast cancer at early stages when most of the times the axila is negative. The
      early diagnoses of breast cancer makes the sentinel node technique a relevant
      tool at the time of making therapeutic decisions. We believe that the sentinel
      node technique could predict in many cases the lymph node status without the need
      of a complete axillary dissection of the axila in patients with breast cancer.

PMID- 16972741
TI  - [Current status of hormone therapy during the menopausal transition and post
      menopause].
AB  - Starting from prospective clinical studies that have evaluated its benefits and
      risks, hormone replacement therapy in menopause women has been reassessed in its
      indications in the last four years. In October, 2004 a Latinamerican Experts
      Consensus was carried out, such report with some modifications is presented in
      this publication. The conclusions the experts reached were the following: 1)
      Hormone Therapy is the gold standard for the control of moderate to severe
      vasomotor symptoms; 2) this therapy must be indicated in an individual manner and
      only in symptomatic women in which the benefit is greater than the risk; 3) the
      least effective dose must be used; 4) it must be used neither for cardiovascular
      prevention, osteoporosis, colon cancer nor for mental disorder; 5) the patient
      must be informed about the benefits and risks.

PMID- 16972742
TI  - [Cervical cancer prevention: an update].
AB  - It has been seen an increase of the cervical cancer and of intraepithelial cancer
      in the last years. The most important risk factors for cervical cancer are sexual
      conduct, early of sexual relationships, number of partners, cigarettes, oral
      anticonceptive, pregnancy, immunosuppression, sexually transmitted illness. And
      an important role of the Human Papilloma Virus. The HPV has been classified in 3
      groups; low risk, the most frequents are 11 and 6, middle risk, tipe 31, 33 and
      35, and high risk, 16 and 18, that have frequent association with cervical cancer
      and with high grade intraepithelial lesions. The cervicovaginal citology is still
      the most accurate diagnosis method to detect SIL or CIN and invasive cancer in
      early stages, it is discussed the periodicity and group of women to whom the
      method must point. There are different options depending if it is a SIL of low or
      high grade or and cancer. With the possibility of doing follow up or treatment,
      such as. LLETZ, Laser, Criotraphy, cone and interferon for the preneoplastic
      lesions. The achievement of a vaccine for HPV could have a significant impact on
      these pathology.

PMID- 16972743
TI  - [Reproductive health today].
AB  - Sexual and Reproductive Health are considered at present as a Human Right that
      must be guaranteed by the State. In Argentina some Federal, Provincial and
      Municipal Laws have been sanctioned in order to guarantee this right through
      programs that bring information, counselling and implementation in the use of
      contraceptive methods, prevention, diagnosis and treatment of sexually
      transmitted infections and genitomammary pathologies. Many Institutions,
      including Universidad Nacional de Cordoba, have been incorporated in these
      programs. Contraceptive methods have selection criteria and indication for its
      use that are described in this publication, for the purpose to explain
      indications, side-effects, advantages and disadvantages of each one of them; as
      well as their best usefulness in the three stages of reproductive life:
      adolescence, sexual maturity and premenopause. Finally, the Eligibility Criteria
      were synthetized for the use of contraceptive methods, performed by the OMS in
      1996.

PMID- 16972744
TI  - [Oncologic indications and contra-indications for hormones use in menopause].
AB  - The life expectation has been changeable the manner of menopause handling. At the
      same time, the women after fifty have the highest incidence of cancer. The
      hormonal replacement therapy (HT) to date have very few indication for patients
      with cancer. The oncologic contraindication for HT are analysed in detail,
      particulary for breast tumor. At the present time, the studies and the
      metanalysis on HT and breat cancer not showed a quantitative increase on the
      risk. We are looking for selective hormone with antagonist for endometrium and
      breast receptors, and effectiveness on the others areas.

PMID- 16972745
TI  - [Cardiovascular disease and hormone therapy. Current status of the controversy].
AB  - The cardiovascular effects of female sex steroids have many faces and are very
      complex. To make this situation even more complicated different therapeutic
      regimens, types, dosages or routes of administration may exhibit different
      effects of estrogens and progestines in postmenopausal women. Furthermore, the
      interpretation of population studies may be problematic by itself, in view of so
      many confounders and biases involved and methodological flaws that sometimes are
      discovered only post-hoc. It seems therefore, that in such a complicated
      situation making definite conclusions and guidelines is almost an impossible
      task. Our suggestion to clinicians is to try and follow the main stream of
      clinical data, looking at the general picture rather than the small details, and
      try to individualize therapy in order to maximize the benefits and minimize the
      adverse reactions and risks. This article discusses the current knowledge on
      hormone replacement therapy and the cardiovascular system. It is not an overview
      since data are vast, but in the post-WHI era this chapter presents current ideas
      and trends in this field to be used by people who practice menopause medicine for
      their own clinical decisions.

PMID- 16972746
TI  - The dysmorphic cervical spine in Klippel-Feil syndrome: interpretations from
      developmental biology.
AB  - The authors conducted a study to identify radiological patterns of Klippel-Feil
      syndrome (KFS), and they present a new interpretation of the origin of these
      patterns based on recent advances in understanding of embryonic development of
      the spine and its molecular genetic control. The authors studied radiographs and
      computerized tomography (CT) scans as well as magnetic resonance images or CT
      myelograms obtained in 30 patients with KFS who were referred for treatment
      between 1982 and 1996; the patients had complained of various neuroorthopedic
      complications. Homeotic transformation due to mutations or disturbed expression
      of Hox genes is a possible mechanism responsible for C-1 assimilation, which was
      found to have occurred in 19 cases (63%). Notochordal defects and/or signaling
      problems, which result in reduced or impaired Pax-1 gene expression, may underlie
      vertebral fusions. This, together with asymmetrical distribution of paraxial
      mesoderm cells and a possible lack of communication across the embryonic midline,
      could cause asymmetrical fusion patterns, which were present in 17 cases (57%).
      The wide and flattened shape of the fused vertebral bodies and their resemblance
      to the embryonic cartilaginous vertebrae as well as the process of progressive
      bone fusion with age suggest that the fusions occur before or, at the latest,
      during chondrification of vertebrae. The authors suggest that the aforementioned
      mechanisms are likely to be, at least in part, responsible for the observed
      patterns in KFS that affect the craniovertebral junction and the cervical spine.

PMID- 16972747
TI  - Inflammatory bowel disease and the craniocervical junction.
AB  - Rheumatological complications have been described in up to 30% of patients being
      followed for inflammatory bowel disease. The majority of these complications
      occur as spondylitic changes in the lumbar spine. Erosive arthritic disease
      associated with inflammatory bowel disease occurs less frequently, but it can
      result in ligamentous laxity and joint instability. To highlight the potential
      significance of the process at the craniocervical junction, the authors describe
      the long-term follow-up care of a complicated case. A 56-year-old woman, with a
      long history of ulcerative colitis, presented with atlantoaxial instability and
      underwent a C1-3 fusion; however, the presence of significant occipitoatlantal
      instability was not recognized. This resulted in high cervicomedullary
      quadriplegia, requiring traction reduction and a combined anterior transoral
      decompressive-posterior occipitocervical fusion. The patient's neurological
      deficit completely resolved postoperatively.

PMID- 16972748
TI  - Pathogenesis, dynamics, and management of os odontoideum.
AB  - Os odontoideum is an uncommon craniovertebral junction (CVJ) abnormality that
      exists as a separate ossicle apart from a hypoplastic dens. It usually moves with
      the clivus or the anterior arch of C-1 (dystopic) or rarely with the dens
      (orthotopic). Its genesis and natural history have been debated, and its proper
      treatment remains uncertain. Two hundred and sixty patients, with symptomatic os
      odontoideum, were evaluated by the author over a 20-year period; the author
      performed surgery in 134 of these patients. In a prospective study the author
      evaluated the early childhood history of trauma, the dynamic studies of motion,
      and the effects of traction by using pleuridirectional tomography, computerized
      tomography (CT), CT myelography and magnetic resonance (MR) imaging. Operative
      findings were documented. Early childhood trauma to the CVJ was recorded in 74
      patients, in 30 of whom normal odontoid processes were documented at initial
      examination prior to the patient reaching age 4 years. Acute neurological
      deterioration following trauma occurred in 63 of 134 patients. Symptoms were
      insidious in 71 of 134 patients. In six patients, who presented with acute
      neurological deterioration after trauma and in whom an abnormal spinal cord
      signal in the cervicomedullary junction was demonstrated on MR imaging, normal
      CVJ motion dynamics were shown. Motion dynamics varied and were unique to each
      patient. Irreducible ventral CVJ disease causing cervicomedullary compromise
      occurred in 28 patients in whom a transpharyngeal ventral decompressive procedure
      was necessitated. During the transoral operation, the transverse portion of the
      cruciate ligament was found to be located anterior to the axis body. All patients
      required dorsal CVJ arthrodesis, which, in 46, was limited to the C1-2 segment.
      Instability at the C1-2 joints was always multidirectional, as demonstrated on
      preoperative neuroimaging studies as well as at operation. Sixteen patients
      presented after completed primary C1-2 dorsal fusion and with worsening deficits.
      They improved when the range of the fusion was extended to the occiput or if the
      ventrally located lesion was excised. Os odontoideum is associated with early
      childhood trauma and is an acquired phenomenon. The presence of abnormal motion
      dynamics necessitates surgical intervention as do associated neurological
      deficits. Asymptomatic patients in whom os odontoideum is incidentally discovered
      and in whom no abnormal motion dynamics are demonstrated should be followed
      closely.

PMID- 16972749
TI  - Instability of the craniovertebral junction and treatment outcomes in patients
      with Down's syndrome.
AB  - Operative intervention for the treatment of instability at the craniovertebral
      junction in patients with Down's syndrome has become somewhat controversial
      because some authors have reported high surgery-related complication rates and
      suggested that the incidence of neurological abnormality associated with this
      abnormal motion may be low. In this report, the authors describe the clinical and
      radiographic findings in 33 patients treated at their institution. Common
      presenting symptoms included neck pain (14 patients), torticollis (12 patients),
      and myelopathy manifested as hyperreflexia (21 patients), or varying degrees of
      quadriparesis (11 patients). Four patients suffered acute neurological insults,
      two after receiving routine general anesthetics for minor surgical procedures and
      two other patients following minor falls. Atlantoaxial instability was the most
      common abnormality documented on radiography (22 patients). Atlantooccipital
      instability (15 patients) was also frequently observed and was coexistent with
      the presence of atlantoaxial luxations in 14 patients. A rotary component of the
      atlantoaxial luxation was present in 13 cases. In 17 patients bony anomalies were
      present, the most frequent of which was os odontoideum (10 patients). Twenty-four
      patients underwent operative intervention, and successful fusion was achieved in
      23. In six of nine patients with basilar invagination, reduction was achieved
      with preoperative traction and thus avoided the need for ventral decompressive
      procedures. There were no cases of postoperative deterioration, and 22 patients
      made excellent or good recoveries. The results of this series highlight the
      clinicopathological phenomena of craniovertebral instability in patients with
      Down's syndrome and suggest that satisfactory outcomes can be achieved with a low
      rate of surgical morbidity.

PMID- 16972750
TI  - Comprehensive approach to Chiari malformation in pediatric patients.
AB  - Chiari malformation is a developmental disorder that is often associated with
      other abnormalities of the cerebrospinal axis. Despite widespread recognition of
      this association, there is relatively little information on the treatment of
      these coexisting disorders in the setting of cerebellar tonsillar ectopia. In an
      effort to improve the care provided to pediatric patients with Chiari
      malformations the authors reviewed their management practices over the last 20
      years. Specifically, they recorded presenting symptoms, radiological studies,
      comorbidities, and management (surgical and nonsurgical) of 112 patients (all <
      20 years of age) with Chiari malformation without myelodysplasia. They found an
      associated syrinx in 29% of patients, basilar invagination in 17%, and scoliosis
      in 14%. The basal angle varied from 120 to 190 degrees and Boogard's angle varied
      from 120 to 220 degrees ; both angles were larger than those measured in normal
      controls. The vertical height of the posterior fossa was shortened and the volume
      decreased as compared with normal controls. The surgical management of this group
      of patients included posterior decompressive (44%), combined transoral and
      posterior decompressive (31%), combined posterior decompressive and posterior
      fusion (8%), and multiple posterior decompressive procedures in the same patient
      (5%). The authors conclude that pediatric patients with a Chiari malformation
      should be specifically examined for evidence of additional craniovertebral
      malformations so that procedures are directed at correcting both the
      comorbidities and the herniation of the cerebellar tonsils through the foramen.

PMID- 16972751
TI  - Biomechanical analysis of cranial settling after transoral odontoidectomy.
AB  - The authors conducted a biomechancial study to determine whether C-1 ring
      integrity is important in maintaining normal occiput-C-2 separation, specifically
      when the anterior arch is transected to provide access to the dens during an
      odontoidectomy procedure. Six human cadaveric occiput-C3 specimens were loaded
      under axial compression, and the bilateral horizontal separation of the C-1
      lateral masses and the vertical compression of the occiput relative to C-2 were
      recorded. Specimens were first studied after odontoidectomy without C-1 ring
      transection, then after C-1 anterior arch transection, and finally after C-1
      lamina transection. With applied compressive load corresponding to three times
      the weight of the head, the C-1 ring spread horizontally 1.57 +/- 0.30 mm more
      when the anterior arch of C-1 was transected than when left intact, resulting in
      0.74 +/- 0.44 mm collapse in the occiput-C-2 vertical separation. After laminar
      transection, the C-1 ring spread 6.55 +/- 2.29 mm more than when it was intact.
      The resultant vertical separation was a 3.37 +/- 1.89-mm collapse in the occiput
      C-2. All changes in C-1 spreading and the occiput-C-2 collapse were statistically
      significant (p < 0.05, paired Student's t-tests). The C-1 ring continuity
      prevents horizontal spreading caused by the wedging of C-1 between the occiput
      and C-2 and thus prevents cranial settling. Therefore, to prevent the subsequent
      development of disease related to cranial settling, the authors recommend that
      the surgeon resect part of C-1 only if necessary during odontoidectomy.

PMID- 16972752
TI  - Image-injected frameless stereotactic approach to the anterior craniovertebral
      junction.
AB  - Transoral odontoidectomy is often performed in the treatment of cervicomedullary
      junction disease. The operating microscope is frequently used to improve
      visualization in this narrow field of view. In the setting of complex anatomy or
      surgical revision the authors hypothesized that combining frameless stereotactic
      technique with intraoperative microscopy would improve the ability to visualize
      and identify intraoperative anatomy. In addition they believed that the ability
      to visualize the targeted region directly in the operating microscope "image
      injection" would be of particular interest in this setting, provided that
      sufficient accuracy for use could be obtained in the registration process. The
      authors assessed the efficacy of this approach in a cadaveric model and obtained
      sufficient accuracy to warrant use in the operating room. This technique was
      applied in the surgical management of a 56-year-old woman with rheumatoid
      arthritis who had undergone a previous decompressive transoral procedure.
      Subsequently she suffered progressive deterioration and was found to have
      residual bony compression of the anterior cervicomedullary junction. The authors
      performed decompressive surgery and obtained satisfactory results by using the
      image-injected technique, and the patient experienced subsequent clinical
      improvement. The authors conclude that the image-injected frameless stereotactic
      technique is of potential benefit, particularly in the narrow window of approach
      of the transoral odontoidectomy.

PMID- 16972753
TI  - Cytogenetic studies in human blood lymphocytes exposed in vitro to 2.45 GHz or
      8.2 GHz radiofrequency radiation.
AB  - Peripheral blood samples collected from healthy human volunteers were exposed in
      vitro to 2.45 GHz or 8.2 GHz pulsed-wave radiofrequency (RF) radiation. The net
      forward power, average power density, mean specific absorption rate, and the
      temperature maintained during the 2-h exposure of the cells to 2.45 GHz or 8.2
      GHz were, respectively, 21 W or 60 W, 5 mW/cm(2) or 10 mW/cm(2), 2.13 W/kg or
      20.71 W/kg, and 36.9 +/- 0.1 degrees C or 37.5 +/- 0.2 degrees C. Aliquots of the
      same blood samples that were either sham-exposed or exposed in vitro to an acute
      dose of 1.5 Gy gamma radiation were used as unexposed and positive controls,
      respectively. Cultured lymphocytes were examined to determine the extent of
      cytogenetic damage assessed from the incidence of chromosomal aberrations and
      micronuclei. Under the conditions used to perform the experiments, the levels of
      damage in RF-radiation-exposed and sham-exposed lymphocytes were not
      significantly different. Also, there were no significant differences in the
      response of unstimulated lymphocytes and lymphocytes stimulated with
      phytohemagglutinin when exposed to 8.2 GHz RF radiation. In contrast, the
      positive control cells that had been subjected to gamma irradiation exhibited
      significantly more damage than RF-radiation- and sham-exposed lymphocytes.

PMID- 16972754
TI  - siRNA targeting NBS1 or XIAP increases radiation sensitivity of human cancer
      cells independent of TP53 status.
AB  - NBS1 is essential for the repair of radiation-induced DNA double-strand breaks
      (DSBs) in yeast and higher vertebrate cells. In this study, we examined whether
      suppressed NBS1 expression by small interference RNA (siRNA) could enhance
      radiation sensitivity in cancer cells with different TP53 status. We used human
      non-small cell lung cancer cells differing in TP53 gene status (H1299/wtp53 cells
      bearing wild-type TP53 or H1299/mp53 cells bearing mutant TP53). A DNA cassette
      expressing siRNA targeted for the NBS1 gene was transfected into those cell
      lines, and radiation sensitivity was examined with a colony-forming assay.
      Cellular levels of NBS1 and other proteins were analyzed using Western blotting.
      We found that the radiation sensitivity of H1299/wtp53 and H1299/mp53 cells was
      enhanced by transfection of the DNA cassette. In the NBS1-siRNA-transfected
      cells, we observed decreased constitutive expression of NBS1 protein and
      decreased radiation-induced accumulation of phosphorylated NBS1 protein. In
      addition, radiation-induced expression of the transcription factor NF-kappaB
      (NFKB) and XIAP (X-chromosome-linked inhibitor of apoptosis protein) was
      suppressed by NBS1-siRNA. Enhanced X-ray sensitivity after NBS1-siRNA
      transfection was achieved in TP53 wild-type cells and sensitivity was even more
      pronounced in TP53 mutant cells. The transfection of siRNA targeted for XIAP also
      enhanced X-ray sensitivity even more for TP53 mutant cells compared to TP53 wild
      type cells. Our data suggest that the sensitization to radiation results from
      NBS1-siRNA-mediated suppression of DNA repair and/ or X-ray-induced cell survival
      signaling pathways through NFKB and XIAP. siRNA targeting appears to be a novel
      radiation-sensitizing agent, particularly in human TP53 mutant cancer cells.

PMID- 16972756
TI  - Nucleocytoplasmic transport of plasmid DNA: a perilous journey from the cytoplasm
      to the nucleus.
AB  - Nonviral vectors represent a promising approach for the safe delivery of
      therapeutic DNA in genetic and acquired human diseases. Before synthetic vector
      systems can be used for clinical applications, their limited efficacy must be
      addressed. At the cellular level, successful gene transfer is dependent on
      several additional factors including DNA uptake, release from the DNA-vector
      complex, and nucleocytoplasmic transport. This paper reviews the major metabolic
      and physical impediments that plasmid DNA vectorized by synthetic vectors
      encounters between the cytosol and the nucleus. Plasmid DNA that escapes the
      endolysosomal compartment encounters the diffusional and metabolic barriers of
      the cytoplasm, reducing the number of intact plasmids that reach the nuclear
      envelope. Nuclear translocation of DNA requires either the disassembly of the
      nuclear envelope during cell division or active nuclear transport via the nuclear
      pore complex. In the nucleus, plasmid DNA is relatively stable, but its
      transcription and its fate during cell division are still debated. A better
      understanding of the cellular and molecular basis of nonviral gene transfer
      during nucleocytoplasmic trafficking may provide strategies to overcome those
      obstacles that limit the efficiency of nonviral gene delivery. We review some of
      the current methods of gene transfer mediated by synthetic vectors, highlighting
      systems that exploit our actual knowledge of the nucleocytoplasmic transport of
      plasmid DNA.

PMID- 16972757
TI  - In vivo electroporation for gene therapy.

PMID- 16972758
TI  - Long-term protective immunity induced against Trypanosoma cruzi infection after
      vaccination with recombinant adenoviruses encoding amastigote surface protein-2
      and trans-sialidase.
AB  - Protection against protozoan parasite Trypanosoma cruzi has been shown to be
      dependent on the induction of type 1 immune responses. Replication-deficient
      human type 5 recombinant adenoviruses have an unsurpassed ability to induce type
      1 immune responses. Thus, we constructed two type 5 recombinant adenoviruses
      encoding parasite antigens trans-sialidase (rAdTS) and amastigote surface protein
      2 (rAdASP2). Both antigens were genetically engineered to secrete recombinant
      products in order to induce both optimal antibody and T cell responses.
      Immunizations of mice with rAdASP2 and rAdTS induced high levels of serum
      antibodies specific for their recombinant products. In addition, both recombinant
      viruses were able to elicit a biased helper T cell type 1 (Th1) cellular immune
      response and a substantial CD8+ T cell-mediated immune response. Moreover,
      individual immunization with rAdASP2 or rAdTS induced high levels of protection
      against a challenge with live parasites. CD8+ T cells mediated, at least in part,
      such protection. Furthermore, when combined in the same inoculum, rAdTS plus
      rAdASP2 induced complete protection in all animals tested, even when challenges
      were performed 14 weeks after the last immunization. Taking together, these
      results show that recombinant adenoviruses expressing TS and ASP-2 antigens of T.
      cruzi are interesting candidates for the development of a vaccine against Chagas'
      disease.

PMID- 16972759
TI  - Role of integrin cross-regulation in parvovirus B19 targeting.
AB  - Most viral vectors used for gene therapy lack the ability to target a defined
      cell population. Parvovirus B19 has a restricted tropism for human erythroid
      progenitor cells and uses activated alpha5beta1 integrins as coreceptors for
      entry [Weigel-Kelley, K.A., Yoder, M.C., and Srivastava, A. (2003). Blood 102,
      3927-3933]. In this study we examined the role of coexpressed integrins in
      alpha5beta1 integrin coreceptor function. Antibody-mediated cross-linking of
      beta1, beta2, and beta3 integrins and the integrin-associated protein (IAP)
      increased parvovirus B19 entry into nontarget K562 cells. Functional silencing of
      one integrin group, however, reduced the virus uptake- promoting function of a
      subsequently activated integrin group, indicating that the three integrins did
      not operate in isolation but through shared signaling pathways. This was further
      corroborated by direct competition between simultaneously clustered beta2 and
      beta1 integrins that could be overcome by stabilizing clustered beta1 integrins
      in a high-affinity conformation. In contrast, parvovirus B19 entry into primary
      erythroid progenitor cells was characterized by strong clustering-induced beta1
      integrin coreceptor activity that was not abolished by subsequent beta2 and beta3
      integrin activation and was, in fact, substantially increased in the presence of
      preclustered beta2 and beta3 integrins. Thus, integrin function is regulated in a
      cell type-specific manner through coexpressed integrins and preferential
      parvovirus B19 entry into erythroid progenitor cells is promoted by a robust
      beta1 integrin response that is enhanced through stable preclustering of
      coexpressed integrins. These results have implications for other viral vectors
      that use integrins as receptors/coreceptors and for gene therapy of hematopoietic
      progenitor cells using parvovirus B19 vectors.

PMID- 16972760
TI  - Adipose tissue as a novel target for in vivo gene transfer by adeno-associated
      viral vectors.
AB  - Traditionally, skeletal muscle and liver are the preferred target organs for gene
      transfer to supply a transgene product into the systemic circulation. In this
      respect, adipose tissue presents a number of attractive features. However,
      adipose tissue transduction in vivo has not been feasible by conventional
      methods. To solve this issue, we tested the utility of excipients in adeno
      associated virus (AAV) vector-mediated gene transfer and found that Pluronics are
      suitable for this purpose. In a histological analysis of adipose tissue in db/db
      mice, Pluronic F88 showed the greatest augmentative effect on beta-galactosidase
      expression in combination with the AAV1 vector. When the vector encoding mouse
      erythropoietin (Epo) was used in the same manner, increased plasma Epo
      concentrations were observed (230 +/- 80 versus 58 +/- 14 mU/ml). Moreover, the
      plasma Epo concentration returned to the normal level after the surgical removal
      of transduced adipose tissue. No damage was observed in the transduced tissue.
      Our results indicate that the proposed method is safe and efficient for gene
      transfer into adipose tissues, thus providing an alternative for supplemental
      gene therapy.

PMID- 16972761
TI  - Deletion of VAI and VAII RNA genes in the design of oncolytic adenoviruses.
AB  - Deletion of viral functions that can be complemented by the specific phenotype of
      tumor cells is a common strategy to design oncolytic viruses. For example,
      enhanced mRNA cytoplasmic export in tumor cells phenocopies the adenovirus E1B
      55K function and renders mutants of this protein tumor selective. Also, an
      activated RB pathway complements specific E1A functions that can be deleted to
      produce oncolytic viruses. In this paper we demonstrate that an adenoviral mutant
      deleted in virus-associated I (VAI) and VAII RNAs (Ad-VAdel) has oncotropism
      characterized by 100-fold replication deficiency compared with wild-type
      adenovirus in normal cells and an unaffected ability to replicate and kill
      different types of tumor cells. This mutant also displays active antitumoral
      activity in vivo. In contrast, this oncotropism is less evident in a mutant
      expressing an inactive form of VAI (Adsub719) because VAII RNA expression is
      upregulated. The mRNA translation promoted by VA RNA genes can be phenocopied in
      tumor cells with the activation of signal transduction pathways, such as the Ras
      pathway.

PMID- 16972762
TI  - Inhibition of ovarian tumor growth by gene therapy with recombinant soluble
      vascular endothelial growth factor receptor 2.
AB  - The growth and persistence of solid tumors and their metastases are angiogenesis
      dependent. Targeting angiogenesis represents a new strategy for the development
      of antitumor therapies. The extracellular immunoglobulin- like domain of VEGFR-2
      (KDR/Flk-1), soluble VEGFR-2, may form a heterodimeric complex with a wild-type
      VEGF receptor and function as a dominant negative receptor. We assessed the
      effects of sFlk-1 on SKOV3 cell growth and proliferation in vitro. Furthermore,
      we investigated the effectiveness of recombinant soluble Flk-1 adenovirus on
      inhibition of tumor growth in an ovarian tumor (SKOV3) nude murine model,
      combined with cis-diamminedichloroplatinum (DDP). Nude mice bearing SKOV3 tumors
      received adsFlk- 1 (recombinant soluble Flk-1 adenovirus) and DDP, respectively
      or in combination, and tumor growth inhibition, microvessel density, and
      apoptosis in tumor tissue were assessed by immunohistochemical analysis. Our data
      revealed that sFlk-1 had little effect on tumor cell growth in vitro, whereas ad
      sFlk-1 administration could inhibit tumor growth significantly (p < 0.05) in the
      nude murine model, accompanied by angiogenesis suppression and apoptosis
      induction, and augmented efficiency was observed in combination with DDP as well.
      The present findings suggest that gene therapy with ad-sFlk-1 is an efficient
      antiangiogenesis strategy, which may be important in further exploration and
      possible translation into a clinical trial.

PMID- 16972763
TI  - Development of a synthetic promoter for macrophage gene therapy.
AB  - Macrophages have the potential to deliver therapeutic genes to many target
      tissues. Macrophage-specific synthetic promoters (SPs) generated by random
      ligation of myeloid/macrophage cis elements had activity up to 100-fold that of a
      native macrophage promoter in macrophage cell lines, but were minimally active in
      nonmyeloid cells. Mouse bone marrow cells (BMCs) transduced ex vivo with
      lentivectors expressing green fluorescent protein (GFP) driven either by an SP
      (SP-GFP) or a cytomegalovirus (CMV) promoter (CMV-GFP) were used for syngeneic
      transplantation of lethally irradiated mice. Blood leukocytes showed stable GFP
      expression for up to 15 months after transplantation. SP-GFP expression was
      selective for CD11b+ macrophages, whereas CMV-GFP expression was observed in
      erythrocytes, as well as in both CD11b+ and CD11b- leukocytes. Furthermore, SP
      GFP expression was much stronger than CMV-GFP expression in CD11b+ macrophages.
      apoE-/- BMCs transduced with the lentiviral vector encoding human apoE were used
      to transplant apoE-/- mice. Macrophage expression of apoE from 10 to 26 weeks of
      age significantly reduced atherosclerotic lesions in recipient apoE-/- mice.
      Thus, the novel SPs, especially when combined with lentivectors, are useful for
      macrophage-specific delivery of therapeutic genes.

PMID- 16972764
TI  - Modulating target site selection during human immunodeficiency virus DNA
      integration in vitro with an engineered tethering factor.
AB  - The mechanisms controlling retroviral integration have been the topic of intense
      interest, in part because of adverse clinical events that occurred during
      retrovirus-mediated human gene therapy. Here we investigate the use of artificial
      tethering interactions to constrain retroviral integration site selection in an
      in vitro model. During normal infection, HIV DNA integration is favored in active
      cellular transcription units. One component of the targeting mechanism is the
      cellular LEDGF/p75 protein. LEDGF/p75 binds tightly to HIV integrase (IN)
      protein, and depletion of LEDGF/p75 from target cells results in reduced
      integration in transcription units, suggesting integration targeting by a
      tethering mechanism. We constructed and analyzed fusions of LEDGF/p75 or its IN
      binding domain (IBD) to the DNA-binding domain of phage lambda repressor protein
      (lambdaR). In the presence of the lambdaR-LEDGF/p75 fusions, increased strand
      transfer by IN was seen in target DNA near lambdaR-binding sites in vitro . These
      data support the idea that a direct interaction between LEDGF/p75 and IN can
      mediate targeting via a tethering mechanism, and provide proof of concept for the
      idea that protein-protein interactions might be engineered to constrain
      integration site selection during human gene therapy.

PMID- 16972766
TI  - Nectar and pollen feeding by insect herbivores and implications for multitrophic
      interactions.
AB  - Among herbivorous insects with a complete metamorphosis the larval and adult
      stages usually differ considerably in their nutritional requirements and food
      ecology. Often, feeding on plant structural tissue is restricted to the larval
      stage, whereas the adult stage feeds primarily or exclusively on plant-provided
      food supplements such as nectar and pollen. Research on herbivore nutritional
      ecology has largely been divided along these lines. Most studies focus on actual
      herbivory by larval stages, while nectar and pollen feeding by adult herbivores
      has been addressed mainly in the light of plant-pollinator interactions. Only
      recently have we started to realize that the two phenomena are closely
      interlinked and that nectar and pollen feeding by adult herbivores can have a
      strong impact on plant-herbivore interactions. Here we address this largely
      ignored aspect of multitrophic level interactions and discuss its wide-ranging
      implications.

PMID- 16972767
TI  - Insect/mammal associations: effects of Cuterebrid bot fly parasites on their
      hosts.
AB  - The effect of parasites on their hosts has implications for basic and applied
      ecology (e.g., species' population dynamics and distributions, biological
      control, and threats to at-risk species) and coevolution. Cuterebrid bot flies
      comprise one of the most-studied groups of insect parasites of mammals. Interest
      in their impact dates from at least 1857, when Cuterebra emasculator was so named
      because of the erroneous belief that its larvae castrate their hosts. This review
      addresses the effects of cuterebrid larvae on host biochemistry, physiology,
      behavior, and ecology. Despite high prevalence (peak values commonly range from
      30% to 70%), at average intensities (one to three larvae per host) these
      parasites generally have little effect on the fitness or population dynamics of
      their typical hosts. This outcome likely reflects parasite/host coevolution
      favoring parasites that minimize harmful effects on hosts required for their
      survival and hosts that best tolerate perennial parasites they cannot avoid. In
      contrast, aggravated effects occur at higher intensities and with atypical hosts.
      Additional field studies involving experimental manipulation of infestation and
      spanning more than a few seasons are required to confirm these conclusions.

PMID- 16972768
TI  - The hygiene hypothesis and foodborne illnesses: too much of a good thing, or is
      our food supply too clean?

PMID- 16972769
TI  - Foodborne disease trends and reports.

PMID- 16972770
TI  - Public health significance of antimicrobial-resistant gram-negative bacteria in
      raw bulk tank milk.
AB  - The dairy farm environment and animals on the farm serve as important reservoirs
      of pathogenic and commensal bacteria that could potentially gain access to milk
      in the bulk tank via several pathways. Pathogenic gram-negative bacteria can gain
      access to bulk tank milk from infected mammary glands, contaminated udders and
      milking machines, and/or from the dairy farm environment. Contaminated raw milk
      when consumed by humans or fed to animals on the farm can result in gastroenteric
      infections in humans and animals and also provide an opportunity for organisms to
      colonize the farm environment. This scenario becomes much more complicated when
      pathogenic bacteria such as Salmonella, Shiga toxin-producing Escherichia coli,
      and commensal gram-negative enteric bacteria encode for antimicrobial resistance
      determinants. In recent years, the role of commensal bacteria as reservoirs of
      genetic determinants for antimicrobial resistance has come under closer scrutiny.
      Commensal bacteria in bulk tank milk can be a significant reservoir of
      antimicrobial determinants. Raw milk consumption can result in exposure to
      antimicrobial-resistant commensal gram-negative bacteria. This paper examines the
      prevalence and role of commensal gram-negative enteric bacteria in bulk tank milk
      and their public health significance.

PMID- 16972771
TI  - Fecal prevalence of Escherichia coli O157, Salmonella, Listeria, and
      Bacteriophage Infecting E. coli O157:H7 in feedlot cattle in the Southern Plains
      region of the United States.
AB  - Escherichia coli O157:H7, Salmonella, and Listeria are foodborne pathogens of
      critical importance that often colonize cattle. E. coli O157:H7 can be
      specifically killed by lytic bacteriophage, and lytic bacteriophage treatment has
      been suggested as a pre-harvest intervention strategy to reduce foodborne
      pathogens in cattle. To date, no systematic approach to determine the incidence
      of E. coli O157:H7-infecting lytic bacteriophage has been published. Therefore,
      the current study was designed to determine (1) the incidence of E. coli O157,
      Salmonella spp., and Listeria and (2) the incidence of E. coli O157:H7-infecting
      bacteriophage in the feces of feedlot steers in commercial feedlots in the United
      States. Fecal samples (n=60) were collected from four feedlots in two Southern
      Great Plains states (total (n=240 fecal samples). Salmonella and E. coli O157:H7
      were found in 3.8% and 11.7% of the fecal samples, respectively. Bacteriophage
      targeting E. coli O157:H7 were found in all four feedlots, in 15% of the
      individual fecal samples, and in 55% of the cattle pens. Our results indicate
      that such bacteriophage are widespread in feedlot cattle, suggesting that further
      research into the ecological role of bacteriophage in the gastrointestinal tract
      is needed.

PMID- 16972772
TI  - Evaluation of immunomagnetic separation-polymerase chain reaction in direct
      detection of Brucella abortus and Brucella melitensis from cheese samples.
AB  - The current study was carried out to assess the use of immunomagnetic separation
      polymerase chain reaction (IMS-PCR) in direct detection of Brucella abortus and
      B. melitensis from soft cheese and to examine a relatively small number of field
      samples for the presence of these species. Two methodologies, one with IMS and
      the other without IMS, were employed for recovery of the Brucella species from
      cheese samples. IMS in conjunction with the PCR assay was determined to detect as
      low as 3x10(2) bacteria/mL, while the limit of detection with the other
      extraction procedure was 3x10(3) bacteria/mL. In the analysis of 40 cheese
      samples collected from various markets, only B. abortus was detected by PCR using
      both DNA extraction procedures in two (5%) samples. No positive results were
      obtained by culture and B. melitensis was not found in any cheese samples
      examined. The results suggest that this technique is promising owing to its pace
      and high sensitivity and should aid in direct detection of Brucella species from
      complex food samples.

PMID- 16972773
TI  - Pulsed-field gel electrophoresis patterns of Escherichia coli O157 isolates from
      Kansas feedlots.
AB  - This study investigated the prevalence and distribution of Escherichia coli O157
      genetic types within and among feedlots using pulsed-field gel electrophoresis to
      separate XbaI-digested DNA. The study population consisted of 300 pens of cattle
      in 30 feedlots in Kansas that were sampled (feces, water, and water sediment)
      within a month of being shipped for slaughter. The prevalence of E. coli O157 was
      8.5% in feces, 3.1% in water, and 4.5% in water sediment samples. A total of 424
      E. coli O157 isolates were characterized by pulsed-field gel electrophoresis, and
      139 subtypes (100% Dice similarity with no band differences) were identified. The
      majority of subtypes (70/139) was identified only once, but nine were identified
      10 or more times. Identical subtypes were recovered from both feces and water
      tanks in 10 feedlots. The majority of subtypes were identified in only one
      feedlot, and the number of subtypes ranged from one to 23 within a feedlot and
      from one to seven within a pen. There were 10 feedlots with at least 15 positive
      samples. In these 10 feedlots, the most common subtype accounted for 16.9-78.6%
      of the isolates. Common subtypes differed among feedlots. In eight of the 10
      feedlots, the most common subtype was identified in multiple pens. The results
      support a complex ecology for E. coli O157 in feedlot operations, with factors
      associated with exposure and transmission likely acting at a common level for
      multiple feedlots, within feedlots, and within pens of cattle.

PMID- 16972774
TI  - Genetic characterization of a diverse Escherichia coli O157:H7 population from a
      variety of farm environments.
AB  - Many of the current studies on the genetic diversity of Escherichia coli O157:H7
      have focused on pathogenic clinical, veterinary, or food isolates. These studies
      did not explore the diversity of the larger population in the farm environment.
      Research on selected farm isolates address this wider diversity but have
      typically been limited to a specific geographic locale or farm type, thus giving
      limited insight into the greater diversity across geographic regions and varied
      environments. The objective of this study was to evaluate a diverse population of
      E. coli O157:H7 collected from a variety of locations and farm environments.
      Eighty-eight isolates were collected from four farm types (swine, dairy, beef,
      and poultry) across the southeastern and western United States. Eighteen farms
      were sampled every 3 months over a period of 24 months. Isolates were analyzed by
      ribotyping and pulsed field gel electrophoresis (PFGE). Real-time PCR was used to
      determine the presence or absence of key pathogenic genes (stx1, stx2, and eae).
      The data indicate a significant amount of genetic diversity, however, ribotype
      analysis revealed meaningful clusters within the larger population. These
      groupings were consistent with PFGE analysis. Most of these isolates were
      clustered by location (i.e. from the same state or region) or farm type. Of the
      isolates in these clusters, most did not contain pathogenic genes. Of notable
      interest is a single group in which the majority of isolates, collected from four
      of the five states sampled, contained at least one stx gene and the eae gene
      suggesting the existence of a specific pathogenic cluster. These data suggest
      that, while there is notable diversity within the broader E. coli O157:H7
      population, pathogenic isolates may be limited to a subset of strains within the
      population.

PMID- 16972775
TI  - Demographic risk factors and incidence of Salmonella enteritidis infection in
      Michigan.
AB  - Salmonella Enteritidis is a major cause of foodborne disease worldwide. In the
      United States, this serotype has been associated with significant morbidity and
      mortality accounting for about 17% of all human Salmonella infections. Data on
      risk factors associated with serotype-specific Salmonella infections have not
      been reported in Michigan before. We carried out this study using surveillance
      data to identify high-risk groups and regions for S. Enteritidis infection in
      Michigan. Results of this study may be used to develop better control and
      prevention measures against this common foodborne pathogen. We analyzed data on
      Salmonella infections collected by the Michigan Department of Community Health's
      surveillance system (1995-2001). We computed age, gender, and place of residence
      specific incidences of S. Enteritidis infection in Michigan using population
      based denominators. We used Poisson regression analysis to study the associations
      between S. Enteritidis infection and certain predictor demographic variables,
      while controlling for confounders and covariates. We found an overall
      1.87/100,000 average annual S. Enteritidis incidence with 1.91/100,000 in females
      and 1.81/100,000 in males. A higher incidence of S. Enteritidis infection was
      associated with Michigan children<5 years old when compared with average national
      estimates (p<0.01). The final adjusted Poisson model revealed that children<1
      year of age [RR: 9.75, CI: 7.99-11.90] and children 1-4 years of age [RR: 3.37,
      CI: 2.83-4.02] are at higher risk for S. Enteritidis infection compared to adults
      aged 15-39 years. No significant differences in incidence of S. Enteritidis
      infections were found between urban and rural dwellers or between genders
      (p>0.05). The incidence rate of S. Enteritidis infection in the Michigan
      pediatric population (<5 years) was found to be significantly higher than average
      national estimates, meriting immediate public health attention. Risk factors for
      S. Enteritidis infection in Michigan children should be identified in order to
      devise effective control and prevention measures.

PMID- 16972776
TI  - Prevalence of enterotoxin and toxic shock syndrome toxin genes in Staphylococcus
      aureus isolated from milk of cows with mastitis.
AB  - Staphylococcus aureus isolated from milk of cows with mastitis were evaluated for
      the prevalence of 16 enterotoxin genes (sea-see and seg-seq) and toxic shock
      syndrome toxin gene (tsst-1). Of 78 S. aureus examined, 73 (93.6%) were positive
      for one or more enterotoxin genes and these were divided into 36 groups by the
      presence of different enterotoxin genes. Enterotoxin genes including sen (84.6%),
      sem (71.8%), sei (60.3%) and sed (52.6%) were found frequently, while seg
      (24.4%), seq (16.7%), seo (12.8%), and seb (1.3%) were found at lower
      frequencies. Toxic shock syndrome toxin (tsst-1) gene was detected in 20 (25.6%)
      isolates and was always found in combination with other enterotoxin genes. The
      majority (88.5%) harbored more than one enterotoxin gene in different
      combinations. Eight S. aureus isolates (10.3%) were positive for sed, sei, sem,
      and sen; six (7.7%) possessed sed, seg, sei, sem, sen, and tsst-1; five (6.4%)
      had sei, sem, and sen; and four (5.1%) had sei, and sen. One isolate was positive
      for seb along with other SE genes including sed, seh, sem, sen, seq, and tsst-1.
      None of the isolates carried other enterotoxin genes (sea, sec, see, sej, sek,
      sel, and sep). PFGE profiles revealed 15 distinct pulsotypes among the 78 S.
      aureus isolates evaluated. PFGE and enterotoxin gene profiles did not match with
      each other because a single pulsotype carried different combinations of
      enterotoxin genes. The majority of S. aureus isolated from milk of mastitic cows
      carried newly described SE genes sem, sen and sei along with classical SE genes,
      sed and tsst-1. This is the first report describing the high prevalence of newly
      described enterotoxin genes, sem and sen in S. aureus from bovine mastitis. The
      high prevalence of enterotoxin genes and tsst-1 in S. aureus may be important as
      it is relevant to udder pathogenicity and food hygiene.

PMID- 16972777
TI  - Effect of ionophore supplementation on the incidence of Escherichia coli O157:H7
      and Salmonella and antimicrobial susceptibility of fecal coliforms in Stocker
      cattle.
AB  - To examine the effect of ionophore supplementation on fecal shedding of
      Escherichia coli O157:H7 and Salmonella, crossbred beef calves (n=113; mean body
      weight [BW], 243 kg) were fed a mineral supplement with ionophore (1.76 g
      lasalocid/kg) for 61 days (d). Control calves received an identical mineral
      supplement without lasalocid. Calves were pastured on fescue/bermudagrass
      paddocks and supplemented with a corn/wheat midds/soybean meal supplement (1.5%
      of BW/d). Upon arrival, cattle were fed a commercial receiving ration containing
      1 g chlorotetracycline/kg for 10 d. Sick calves were administered one or a
      combination of the following: Nuflor (florfenicol), Baytril (eurofloxacin),
      Micotil (tilmicosin), or LA 200 (oxytetracycline). Fecal samples were collected
      immediately prior to ionophore supplementation, approximately midway and at the
      end of the experimental period (60 d total ionophore feeding) for isolation of E.
      coli O157:H7 and Salmonella. Putative fecal coliforms were also isolated at these
      sampling times and examined for antimicrobial susceptibility. The study was
      replicated over a two year period (year 1, n=53 head; year 2, n=60 head).
      Ionophore supplementation had no effect (p>0.10) on the incidence of calves
      shedding E. coli O157:H7 or Salmonella. The percentage of calves shedding E. coli
      O157:H7 varied throughout the experimental period from 0 to 30%, while Salmonella
      was cultured from only three calves over the 2-year experimental period.
      Antimicrobial susceptibility profiles of putative fecal coliforms were consistent
      with antibiotic treatments administered during the study (observed resistance to
      chlortetracycline, florfenicol, oxytetracycline), while only one treatment effect
      was observed. Ionophore treatment resulted in a significantly higher number of
      coliform isolates resistant to ampicillin compared to controls in year 1, but not
      year 2. A number of fecal coliform isolates demonstrated resistance to multiple
      antibiotics, however, this was not affected (p>0.10) by ionophore
      supplementation. Mineral intakes, BW gain, and the number of sick calves were
      similar (p>0.10) among treatments. Ionophore supplementation had no affect on
      fecal shedding of E. coli O157:H7 or Salmonella and a negligible impact on
      antimicrobial susceptibility patterns of fecal coliforms in beef calves.

PMID- 16972778
TI  - Involvement of closely related strains of a new clonal group of Listeria
      monocytogenes in the 1998-99 and 2002 multistate outbreaks of foodborne
      listeriosis in the United States.
AB  - In 1998-99, a multistate outbreak of listeriosis in the United States was
      associated with contaminated hot dogs and was caused by a strain of Listeria
      monocytogenes serotype 4b that had been only rarely encountered before in the
      national PulseNet database. Upon further characterization, the strains from this
      outbreak were designated as Epidemic Clone II (ECII). ECII isolates exhibited
      diversification in a genomic region ("region 18") that was otherwise conserved
      among L. monocytogenes of serotype 4b. Additional unique genetic markers were
      identified through genome sequencing of one of the isolates from the 1998-99
      outbreak. In 2002, another multistate outbreak of listeriosis also involved
      bacteria of serotype 4b and was attributed to contaminated turkey deli meats.
      Molecular subtyping data revealed that the macrorestriction patterns of the
      isolates from the 1998-99 and 2002 outbreaks were closely related. In addition,
      the 2002 outbreak isolates harbored chromosomal genetic markers found to be
      unique to, and typical of, the 1998-99 outbreak isolates, including
      diversification in genomic region 18. Macroarray- based subtyping using
      chromosomal sequences confirmed the close genetic relatedness between the
      isolates from the two outbreaks. Genomic content was highly conserved among
      isolates from each outbreak, with differences detected only in prophage and
      internalin-like gene sequences. However, since these differences were observed
      among isolates from each of the outbreaks, they did not differentiate the 1998-99
      isolates as a group from those of the 2002 outbreak. Two of 15 randomly chosen
      serotype 4b clinical isolates from a non-outbreak period (calendar year 2003)
      appeared to be closely related to the 1998-99 and 2002 outbreak isolates. These
      findings suggest that both multistate outbreaks of listeriosis in the United
      States involved closely related members of a single clonal group (ECII) that had
      not been identified in outbreaks prior to 1998. Since the outbreaks involved
      different food vehicles and processing plants, the findings suggest establishment
      of ECII in a still unidentified reservoir in the United States, from which the
      organisms were introduced to different processing plants.

PMID- 16972779
TI  - Pulsed-field gel electrophoresis of Listeria monocytogenes strains: the PulseNet
      Europe Feasibility Study.
AB  - A feasibility study on standardized subtyping of Listeria monocytogenes by pulsed
      field gel electrophoresis (PFGE) was performed in 2003 in Europe. The aim of the
      project was to identify veterinary, food, and public health reference
      laboratories that were willing to participate in the molecular surveillance of
      Listeria infections in Europe, as is done with PulseNet USA, and to test if the
      participants could generate results that were comparable with each other. A panel
      of strains and the methodology were sent to European laboratories, and images of
      PFGE gels were transferred electronically, then analyzed visually and with image
      analysis software. Only nine out of 43 gels were not fully satisfactory at the
      visual evaluation step stage. Computerized analysis showed that only three out of
      33 gels gave dendrograms totally different from the reference dendrograms. Thus,
      the objectives of the study were met: most human and food European laboratories
      concerned with typing L. monocytogenes participated, images were transmitted
      electronically, and the overall quality of the gels was good.

PMID- 16972780
TI  - Potential of antimicrobial agents to inhibit fungi to aid isolation of
      Campylobacter.
AB  - In preliminary studies conducted to isolate thermophilic Campylobacter spp. from
      cull dairy cow fecal samples, growth of fungal strains on Abeyta-Hunt-Bark agar
      and charcoal cefoperazone desoxycholate agar (CCDA) interfered with isolation of
      target bacteria. Concentrations of antifungal substances in the agar media were
      not effective in suppressing growth of antibiotic resistant fungi. The objective
      of the current study was to determine the efficacy of supplemental antimicrobial
      agents to inhibit growth of fungi of fecal origin on Campylobacter isolation
      media where microbial growth is overwhelmed by fungi. The inhibitory effect of
      rifampicin and seven antimycotic agents--cycloheximide, 5-fluorouracil, 5
      fluorocytosine, sodium propionate, potassium sorbate, nystatin, and amphotericin
      B--was evaluated. Antimicrobial agents were added singly or combined at
      concentrations ranging from 12.3 to 227 mg/L. Incubation was conducted at 42
      degrees C for 24-48 h in gas jars (CO2+H2). The most effective antibiotic
      combinations that inhibited fungal growth without affecting Campylobacter growth
      were CCDA selective supplement SR155E with amphotericin B (59.5 or 114 mg/L) or a
      mixture of rifampicin, 5-fluorocytosine, and nystatin (119 or 227 mg/L each).
      Results of the present study indicate that addition of supplemental antifungal
      agents in the presence of antibiotics such as rifampicin may enhance suppression
      of fungal overgrowth on Campylobacter isolation agar media.

PMID- 16972781
TI  - The arylhydrocarbon receptor: more than a tox story.

PMID- 16972782
TI  - The aryl hydrocarbon receptor and light.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      that has been intensively studied with respect to the toxicity of xenobiotics.
      However, its function in response to light has never been summarized. Here, we
      provide an overview of AhR activation by light with a focus on the role of
      tryptophan in light-induced AhR activation. We discuss the involvement of the AhR
      in different biological rhythms and speculate on the possible role of the AhR in
      UV-induced responses in skin. Furthermore, this review points out future research
      needs in this field.

PMID- 16972783
TI  - The impact of aryl hydrocarbon receptor signaling on matrix metabolism:
      implications for development and disease.
AB  - The aryl hydrocarbon receptor (AhR) was identified as the receptor for polycyclic
      aromatic hydrocarbons and related compounds. However, novel data indicate that
      the AhR binds a variety of unrelated endogenous and exogenous compounds. Although
      AhR knockout mice demonstrate that this receptor has a role in normal development
      and physiology, the function of this receptor is still unclear. Recent evidence
      suggests that AhR signaling also alters the expression of genes involved in
      matrix metabolism, specifically the matrix metalloproteinases (MMPs). MMP
      expression and activity is critical to normal physiological processes that
      require tissue remodeling, as well as in mediating the progression of a variety
      of diseases. MMPs not only degrade structural proteins, but are also important
      mediators of cell signaling near or at the cell membrane through exposure of
      cryptic sites, release of growth factors, and cleavage of receptors. Therefore,
      AhR modulation of MMP expression and activity may be critical, not only in
      pathogenesis, but also in understanding the endogenous function of the AhR. In
      this review we will examine the data indicating a role for the AhR-signaling
      pathway in the regulation of matrix remodeling, and discuss potential molecular
      mechanisms.

PMID- 16972784
TI  - A role for the aryl hydrocarbon receptor in mammary gland tumorigenesis.
AB  - The aryl hydrocarbon receptor (AhR) is an evolutionarily conserved transcription
      factor bound and activated by ubiquitous environmental pollutants. Historically,
      the AhR has been studied for its transcriptional regulation of genes encoding
      cytochrome P450 enzymes, which metabolize many of these chemicals into mutagenic
      and toxic intermediates. However, recent studies demonstrate that the AhR plays
      an important role in the biology of several cell types in the absence of
      environmental chemicals. Here, this paradigm shift is discussed in the context of
      a putative role for the AhR in mammary gland tumorigenesis. Data demonstrating
      high levels of constitutively active AhR in mammary tumors are summarized.
      Particular focus is placed on the likelihood that the AhR contributes to ongoing
      mammary tumor cell growth and on the possibility that the AhR inhibits apoptosis
      while promoting transition to an invasive, metastatic phenotype. A working model
      is proposed that may help explain the sometimes contradictory outcomes observed
      after AhR manipulation and that serves as a blueprint for the design of
      therapeutics which target the AhR in breast cancer. The theme that malignant
      cells reveal the functions for which the AhR has been evolutionarily conserved is
      presented throughout this discussion.

PMID- 16972785
TI  - Evidence supporting the hypothesis that one of the main functions of the aryl
      hydrocarbon receptor is mediation of cell stress responses.
AB  - We have previously proposed that one of the major consequences of activation of
      the aryl hydrocarbon receptor (AhR) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      could be elicitation of 'cell stress response' reactions [Matsumura, Biochem.
      Pharmacol. 66 (2003), 527-540]. This hypothesis was based mainly on the
      similarity between the toxic symptoms, particularly those related to the wasting
      syndrome, and those induced by bacterial endotoxins, namely lipopolysaccharides
      (LPS) in vivo, as well as the biochemical and molecular consequences of their
      toxic actions in vitro. Since the basic action mechanism of LPS as an inducer of
      cell stress responses (CSR) is known to some extent, including knowledge of their
      specific receptors (i.e., toll-like receptors) and their signaling process
      through the inflammatory response messengers, the above comparison offered a good
      point of reference to this subject. Furthermore, the process of constructing this
      hypothesis itself has provided us with a good opportunity to give a fresh view on
      the toxic action patterns of TCDD.

PMID- 16972786
TI  - The arylhydrocarbon receptor repressor (AhRR): structure, expression, and
      function.
AB  - The arylhydrocarbon receptor (AhR) pathway is known to be critical for cellular
      events, especially for those evoked by several environmental chemicals such as
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Whereas the function of the AhR in
      TCDD toxicity is well analyzed, the importance of the recently cloned AhRR in the
      TCDD-stimulated AhR signaling cascade is still unclear. In mammalian tissues, the
      AhRR gene seems to be ubiquitously expressed and its expression is altered by
      various AhR ligands. Basal and induced AhRR mRNA levels were found to be highly
      cell-, tissue- and species-specific. An inhibitory activity of the AhRR on AhR
      signaling was proposed from overexpression studies. However, there are not
      sufficient data showing such functional activity of the AhRR in vivo. This short
      overview summarizes the present knowledge about the AhRR and should stimulate
      research in the AhRR field to elucidate its physiological function and its
      toxicological importance in dioxin toxicity.

PMID- 16972787
TI  - Impact of the arylhydrocarbon receptor on eugenol- and isoeugenol-induced cell
      cycle arrest in human immortalized keratinocytes (HaCaT).
AB  - Fragrances such as eugenol (4-allyl-2-methoxyphenol) and isoeugenol (2-methoxy-4
      propenylphenol), naturally found in reasonable quantities in the essential oils
      of different spices, are not only common causes of contact dermatitis but also
      known for their antiproliferative actions. Previously, we found a cell cycle
      arrest and an arylhydrocarbon receptor (AhR)-mediated activation of cytochromes
      in immortalized keratinocytes (HaCaT) induced by both compounds. In the present
      study we investigated whether the cell cycle arrest of eugenol and isoeugenol is
      mediated by the AhR in HaCaT cells. Analysis of the cell cycle status by
      fluorescence-activated cell sorting (FACS) revealed an arrest of cells (32-34%)
      in the G0/G1 phase induced by both compounds. This was found in synchronized
      HaCaT cells, natural HaCaT, and siRNA AhR transfected HaCaT. The induced G0/G1
      arrests were reduced in the presence of the highly selective AhR antagonist 3'
      methoxy-4'-nitroflavone (MNF). In summary, these results, together with our
      previous findings that both compounds induce translocation of the AhR into the
      nucleus, provide good evidence that the effects of eugenol and isoeugenol in skin
      and keratinocytes are mediated by the AhR. Furthermore, these data suggest that
      the known growth suppressive effects of these compounds in some skin cells may be
      mediated by AhR interactions.

PMID- 16972788
TI  - Aryl hydrocarbon receptor agonists directly activate estrogen receptor alpha in
      MCF-7 breast cancer cells.
AB  - The aryl hydrocarbon receptor (AhR) binds with high affinity to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) and related halogenated aromatics, but also
      binds with lower affinity to structurally diverse exogenous and endogenous
      chemicals. One study reported that 3-methylcholanthrene (3MC) activated the
      estrogen receptor (ER) through the AhR, which acts as co-regulatory protein,
      whereas a recent report showed that 3MC directly bound and activated ERalpha.
      This study also shows that the AhR agonists benzo[a]pyrene, 3,3',4,4'
      tetrachlorobiphenyl, chrysin, 6-methyl-1,3,8-trichlorodibenzofuran, and 3,3'
      diindolylmethane also induce ERalpha-dependent transactivation. Moreover, in
      chromatin immunoprecipitation assays, these compounds induce binding of AhR and
      ERalpha to the CYP1A1 and pS2 gene promoters, which is consistent with their
      activities as both selective AhR modulators (SAhRMs) and selective ER modulators
      (SERMs).

PMID- 16972789
TI  - Identifying target genes of the aryl hydrocarbon receptor nuclear translocator
      (Arnt) using DNA microarray analysis.
AB  - The aryl hydrocarbon receptor nuclear translocator (Arnt) is a basic helix-loop
      helix (bHLH) protein that also contains a Per-Arnt-Sim (PAS) domain. In addition
      to forming heterodimers with many other bHLH-PAS proteins, including the aryl
      hydrocarbon receptor (AhR) and hypoxia-inducible factors 1alpha, 2alpha and
      3alpha, Arnt can also form homodimers when expressed from its cDNA in vitro or in
      vivo. However, target genes of the Arnt/Arnt homodimer remain to be identified.
      In this study, we have elucidated the profile of genes responsive to the
      reintroduction of Arnt expression in an Arnt-deficient mouse hepatoma cell line
      (c4), using DNA microarray analysis. The expression of 27 genes was upregulated
      by 1.5-fold or more in c4 cells infected with a retroviral vector expressing
      mouse Arnt, while no genes were found to be downregulated. Among the upregulated
      genes, BCL2/adenovirus E1B 19 kDa-interacting protein 1 (NIP3), serine (or
      cysteine) proteinase inhibitor, clade E, member 1 (PAI1), and N-myc downstream
      regulated-like (NDR1), were confirmed to be induced by Arnt using real-time PCR.
      We also found that the 5' promoter region of 15 out of 20 upregulated genes
      contain the type 2 E-box 5'-CACGTG-3' Arnt/Arnt binding sequence, consistent with
      the notion that they represent target genes for Arnt.

PMID- 16972790
TI  - Transcriptional signatures of immune cells in aryl hydrocarbon receptor (AHR)
      proficient and AHR-deficient mice.
AB  - The ligand-activated aryl hydrocarbon receptor (AHR) is known to modulate many
      genes in a highly cell-specific manner, either directly or indirectly via
      secondary effects. In contrast, little is known about the effects of AHR
      deficiency on gene expression balance. We compared the transcriptome of CD4 T
      cells from AHR-/- mice and wild-type mice; 390 genes, many of them immunotypic,
      were deregulated in AHR-deficient CD4 cells. TCDD-induced transcriptome changes
      correlated with the AHR expression level in immune cells. However, there was
      little overlap in AHR-dependent transcripts found in T lineage cells or dendritic
      cells. Our results demonstrate flexible gene accessibility for the AHR in immune
      cells. The idea of a universal battery of AHR-responsive genes is not tenable.

PMID- 16972791
TI  - 14-3-3 proteins in membrane protein transport.
AB  - 14-3-3 proteins affect the cell surface expression of several unrelated cargo
      membrane proteins, e.g., MHC II invariant chain, the two-pore potassium channels
      KCNK3 and KCNK9, and a number of different reporter proteins exposing Arg-based
      endoplasmic reticulum localization signals in mammalian and yeast cells. These
      multimeric membrane proteins have a common feature in that they all expose
      coatomer protein complex I (COPI)- and 14-3-3-binding motifs. 14-3-3 binding
      depends on phosphorylation of the membrane protein in some and on multimerization
      of the membrane protein in other cases. Evidence from mutant proteins that are
      unable to interact with either COPI or 14-3-3 and from yeast cells with an
      altered 14-3-3 content suggests that 14-3-3 proteins affect forward transport in
      the secretory pathway. Mechanistically, this could be explained by clamping,
      masking, or scaffolding. In the clamping mechanism, 14-3-3 binding alters the
      conformation of the signal-exposing tail of the membrane protein, whereas masking
      or scaffolding would abolish or allow the interaction of the membrane protein
      with other proteins or complexes. Interaction partners identified as putative 14
      3-3 binding partners in affinity purification approaches constitute a pool of
      candidate proteins for downstream effectors, such as coat components, coat
      recruitment GTPases, Rab GTPases, GTPase-activating proteins (GAPs), guanine
      nucleotide exchange factors (GEFs) and motor proteins.

PMID- 16972792
TI  - The K+ channel gene, Kcnb1: genomic structure and characterization of its 5'
      regulatory region as part of an overlapping gene group.
AB  - Kcnb1 expression is down-regulated in certain types of cardiomyopathy. As a first
      step towards understanding Kcnb1 regulation, we determined its genomic structure
      and characterized its 5'-regulatory region. Two species of Kcnb1 mRNA were found
      to arise from alternative usage of two highly GC-rich promoters (P1, P2). While
      transcripts arising from P1 were mainly detected in brain, P2 transcripts were
      highly expressed in heart and brain. Core regulatory regions were characterized
      for P1 and P2. The mutation of a potential Nur77/Nurr1/NOR-1 binding site,
      NBRE(Kcnb1), conserved in both human and mouse, resulted in a significant
      decrease in basal P2 promoter activity. Luciferase activities of the longest
      promoter-reporter construct reflected the level of endogenous Kcnb1 mRNA in
      myoblast, smooth muscle, and pituitary cell lines. Hyperosmolarity increased
      Kcnb1 mRNA concentration two-fold, mainly at the transcriptional level in clonal
      pituitary cells. These findings provide a basis for future studies of
      (post)transcriptional mechanism(s) down-regulating Kcnb1 expression in a variety
      of cardiomyopathies and point towards a possible involvement of Kcnb1 in
      pituitary cell excitability and secretory activity regulated by osmolarity.

PMID- 16972793
TI  - Structure-based specificity mapping of secreted aspartic proteases of Candida
      parapsilosis, Candida albicans, and Candida tropicalis using peptidomimetic
      inhibitors and homology modeling.
AB  - Secreted aspartic proteases (Saps) of pathogenic Candida spp. represent a
      specific target for antifungal drug development. We synthesized a series of
      peptidomimetic inhibitors with different isosteric groups and modifications at
      individual positions and tested them with purified Saps from C. albicans (Sap2p),
      C. tropicalis (Sapt1p), and C. parapsilosis (Sapp1p). The kinetic parameters
      indicated that all three proteases prefer binding of inhibitors containing bulky
      hydrophobic residues between positions P3 and P3'. The most divergent specificity
      was found for Sapp1p. The sequence alignment of Sap2p, Sapt1p, and Sapp1p, and
      homology modeling of Sapp1p with the crystal structure of Sapt1p and the complex
      of Sap2p with a peptidomimetic inhibitor showed that the overall folds of Sap2p,
      Sapt1p, and Sapp1p are similar. However, the N- and C-terminal loops formed by
      disulfide bonds between residues 47-53 and 258-292 are significantly shorter in
      Sapp1p, and a unique insertion following Tyr 129 in Sapp1p results in the
      formation of a loop that can interact with inhibitor residues. These Sapp1p
      structural differences might lead to its altered susceptibility to inhibition.

PMID- 16972794
TI  - The solution structure of the membrane-proximal cytokine receptor domain of the
      human interleukin-6 receptor.
AB  - The members of the interleukin-6-type family of cytokines interact with receptors
      that have a modular structure and are built of several immunoglobulin-like and
      fibronectin type III-like domains. These receptors have a characteristic cytokine
      receptor homology region consisting of two fibronectin type III-like domains
      defined by a set of four conserved cysteines and a tryptophan-serine-X-tryptophan
      serine sequence motif. On target cells, interleukin-6 (IL-6) initially binds to
      its cognate alpha-receptor and subsequently to a homodimer of the signal
      transducer receptor gp130. The IL-6 receptor (IL-6R) consists of three
      extracellular domains. The N-terminal immunoglobulin-like domain is not involved
      in ligand binding, whereas the third membrane-proximal fibronectin-like domain
      (IL-6R-D3) accounts for more than 90% of the binding energy to IL-6. Here, we
      present the solution structure of the IL-6R-D3 domain solved by multidimensional
      heteronuclear NMR spectroscopy.

PMID- 16972795
TI  - Sequence determination of lychnin, a type 1 ribosome-inactivating protein from
      Lychnis chalcedonica seeds.
AB  - The complete amino acid sequence of lychnin, a type 1 ribosome-inactivating
      protein (RIP) isolated from Lychnis chalcedonica seeds, has been determined by
      automated Edman degradation and ESI-QTOF mass spectrometry. Lychnin consists of
      234 amino acid residues with a molecular mass of 26 131.14 Da. All amino acid
      residues involved in the formation of the RIP active site (Tyr69, Tyr119, Glu170,
      Arg173 and Trp203) are fully conserved. Furthermore, a fast MALDI-TOF experiment
      showed that two out of three cysteinyl residues (Cys32 and Cys115) form a
      disulfide bridge, while Cys214 is in the thiol form, which makes it suitable for
      linking carrier molecules to generate immunotoxins and other conjugates.

PMID- 16972796
TI  - Paired helical filaments contain small amounts of cholesterol,
      phosphatidylcholine and sphingolipids.
AB  - By using qualitative and quantitative high-performance thin layer chromatography
      (hpTLC) we found lipids associated with purified Alzheimer's (AD) paired helical
      filaments (PHF) in an amount of 1.4+/-0.2% of the total anhydrous mass. Compared
      to normal brain tissue these lipids have an unusual lipid class composition. The
      most prominent lipid classes were phosphatidylcholine (PC), cholesterol (CH),
      galactocerebrosides (GC) and sphingomyelin (SM). In addition, the use of micro
      high-performance liquid chromatography (HPLC) in combination with matrix-assisted
      laser desorption and ionisation time-of-flight mass spectrometry (MALDI-TOF-MS)
      allowed the determination of the molecular species of the polar membrane lipid
      classes present in PHF. The lipid pattern of intracellular PHF shows many
      characteristics of the conserved lipid pattern previously described for
      extracellular amyloid fibrils, suggesting similarities in their pathway of
      formation.

PMID- 16972797
TI  - Induction of intracellular signalling in human endothelial cells by the
      hyaluronan-binding protease involves two distinct pathways.
AB  - Recently a novel plasma serine protease with high affinity to hyaluronic acid and
      glycosaminoglycans, such as heparin and heparan sulfate, has been described and
      termed hyaluronan-binding protease (HABP). HABP cleaves kininogen in vitro,
      releasing the vasoactive peptide bradykinin, and activates plasminogen
      activators, suggesting a vascular cell-directed physiological function of this
      novel plasma protease. Here we show that HABP stimulates human umbilical vein
      endothelial cells (HUVECs) by activating two distinct cell-surface receptors. On
      the one hand, HABP releases bradykinin from cell surface-bound or soluble
      kininogen and triggers a bradykinin B2-receptor-dependent mobilisation of
      intracellular Ca2+. On the other hand, HABP activates the p44/42-dependent MAPK
      (ERK1/2) signalling cascade independent of the B2-receptor, but involving the
      fibroblast growth factor receptor-1 and basic fibroblast growth factor. This
      signalling pathway leads to phosphorylation of the kinases Raf, MEK1/2 and
      ERK1/2. The extracellular activity of HABP also affects the gene expression level
      through phosphorylation of two transcription factors, the cAMP-responsive element
      binding protein CREB and the proto-oncogene c-Myc. Our results indicate a
      proangiogenic potential of HABP, which, in combination with a profibrinolytic
      activity, directs the physiological function of this plasma protease to processes
      in which clot lysis, cell motility and neovascularisation are pivotal processes,
      e.g., in wound healing, tissue repair and tumour progression.

PMID- 16972798
TI  - A novel proteolytically processed CDP/Cux isoform of 90 kDa is generated by
      cathepsin L.
AB  - The Cut-like genes code for multiple isoforms of the CDP/Cux transcription
      factor. The full-length protein contains four DNA-binding domains: Cut repeats 1,
      2 and 3 (CR1, CR2 and CR3) and the Cut homeodomain (HD). The p75 isoform is
      expressed from an mRNA that is initiated within intron 20 and contains only CR3
      and HD. The p110 isoform is generated by proteolytic processing by cathepsin L
      and contains CR2, CR3 and HD. In the present study, we show that an additional
      isoform of 90 kDa is expressed in many cell lines of epithelial origin. Mapping
      experiments with deletion mutants indicated that the N-terminus of p90 is located
      upstream of CR2, between amino acids 918 and 938. Indeed, p90 and p110 displayed
      similar DNA-binding and transcriptional activities. The p90 isoform, like p110,
      was found to be generated by proteolytic processing. The steady-state level of
      both p90 and p110 correlated with the level of cathepsin L activity. Importantly,
      co-expression with a cathepsin L mutant that is initiated at downstream AUG sites
      also stimulated the generation of p90 and p110. These results strongly suggest
      that p90, like p110, is generated by cathepsin L isoforms that are devoid of a
      signal peptide.

PMID- 16972799
TI  - Degradation of apolipoprotein B-100 by lysosomal cysteine cathepsins.
AB  - Although the degradation of cellular or endocytosed proteins comprises the normal
      function of lysosomal proteinases, these enzymes were also detected
      extracellularly during diseases such as atherosclerosis. Since lysosomal cysteine
      cathepsins were demonstrated to transform native LDL particles into a
      proatherogenic type, the following study was undertaken to characterize the
      modification of LDL particles and the degradation of apolipoprotein B-100 in more
      detail. LDL was incubated with cathepsins B, F, K, L, S, and V at pH 5.5 and
      under physiological conditions (pH 7.4) for 2 h to mimic conditions of limited
      proteolysis. Gel electrophoretic analysis of the degradation products revealed
      that cathepsin-mediated proteolysis of apolipoprotein B-100 is a fast process
      carried out by all enzymes at pH 5.5, and by cathepsin S also at pH 7.4. Electron
      microscopic analysis showed that cathepsin-mediated degradation of apolipoprotein
      B-100 rendered LDL particles fusion-competent compared to controls. N-Terminal
      sequencing of cathepsin cleavage fragments from apolipoprotein B-100 revealed an
      abundance of enzyme-specific cleavage sites located in almost all structurally
      and functionally essential regions. Since the cleavage sites superimpose well
      with results from substrate specificity studies, they might be useful for the
      development of cathepsin-specific inhibitors and substrates.

PMID- 16972802
TI  - Psychological interventions for distress in cancer patients: a review of reviews.
AB  - We review a decade of review articles concerning psychosocial interventions for
      cancer patients. We find a distinct progression in the tone of interpretations of
      the literature, as better quality studies accumulate and the sophistication of
      reviews improves. The current literature does not make a compelling case for the
      value of these interventions for the typical cancer patient. The bulk of the
      literature reviews in this field take a narrative rather than a systematic
      approach, and serious compromises in standards are necessary to muster an
      adequate set of studies for review. The more rigorous the review, the less likely
      it is to conclude there is evidence that psychological interventions are
      effective.

PMID- 16972803
TI  - Are psychological interventions effective and accepted by cancer patients? I.
      Standards and levels of evidence.
AB  - Different standards and levels of evidence for evaluating the effectiveness of
      psychological interventions for managing distress in cancer patients are
      presented and discussed. We conclude that the strongest evidence comes from
      systematic qualitative and quantitative (i.e., meta-analyses) reviews of the
      relevant literature and that the most appropriate standard of evidence is the
      "preponderance of evidence" rather than "beyond a reasonable doubt." Results of
      four selected qualitative and quantitative systematic reviews of the literature
      are described. The preponderance of evidence furnished by these systematic
      reviews, particularly that gleaned from meta-analyses, suggests that
      psychological interventions are effective in managing distress in cancer
      patients. Although effectiveness may vary as a function of the specific nature of
      the intervention, overall, effectiveness appears strongest for anxiety-related
      outcomes and when participants are prescreened for distress. Different standards
      and indexes for evaluating evidence regarding the acceptability of psychological
      interventions with cancer patients are presented and discussed. The use of simple
      study accrual rates as an index of intervention acceptability is deemed
      inappropriate. We suggest alternative indexes of acceptability and conclude that
      sufficient information does not exist at the present time to draw the conclusion
      that contemporary psychological interventions for managing distress in cancer
      patients are unacceptable.

PMID- 16972804
TI  - Are psychological interventions effective and accepted by cancer patients? II.
      Using empirically supported therapy guidelines to decide.
AB  - We begin our discussion of the efficacy of psychological interventions for cancer
      patients by defining basic terms. We define efficacy using evidence-based
      medicine guidelines. According to these guidelines, an intervention is considered
      efficacious if two or more randomized clinical trials report positive and
      significant outcomes. Using this guideline as well as other evidence-based
      medicine criteria, we rate five recent intervention studies published in top-tier
      journals. The results of this review suggested that there is sufficient evidence
      to conclude that cognitive-behavioral interventions are effective in reducing and
      managing psychological distress in cancer patients and are accepted by these
      patients.

PMID- 16972805
TI  - Efficacy of psychosocial interventions in cancer care: evidence is weaker than it
      first looks.
AB  - With increasing sophistication, successive reviews find weaker evidence for the
      efficacy of psychosocial interventions to reduce distress among cancer patients.
      However, these appraisals may still be overly positive because of reviewers'
      uncritical acceptance of flaws in the design, analysis, and reporting of the
      results of such trials. Using randomized trials from high-impact journals, we
      show confirmatory bias, selective reporting of the most favorable of multiple
      outcome measures, suppressing of null results in subsequent citations of trials,
      and dropping of data for patients least likely to benefit from intervention. The
      conclusion that typical cancer patients do not benefit from interventions to
      reduce distress is strengthened when these endemic problems with the literature
      are taken into account. Required registering of the details of clinical trials
      and adherence to CONSORT reduces but does not eliminate bias in the literature.

PMID- 16972806
TI  - Seeing the forest for the trees: a rebuttal.

PMID- 16972808
TI  - Lost in translation: the need for clinically relevant research on psychological
      interventions for distress in cancer patients.

PMID- 16972809
TI  - Assessment and treatment of depression in patients with cardiovascular disease:
      National Heart, Lung, and Blood Institute working group report.

PMID- 16972810
TI  - An implementation intentions intervention to increase uptake of mammography.
AB  - BACKGROUND AND PURPOSE: This study tested an implementation intentions
      intervention to increase uptake in the United Kingdom's National Health Service
      Breast Screening Programme. The intervention asked women to plan how they would
      overcome up to 3 previously identified barriers to attending. METHODS: In a
      randomized controlled trial, 2,082 participants were allocated to an intervention
      condition, an assessment-only condition, or a nonassessment control condition.
      The intervention condition was designed to help women plan how to change their
      appointment, how to arrange transport, and how to negotiate time off work. The
      assessment-only condition controlled for the possibility that completing a
      questionnaire about mammography might in itself influence attendance, and the
      nonassessment condition was a control against any effect on attendance that mere
      contact with the research team might have. RESULTS: Mean age of respondents was
      56.1 years, and 99.4% were White British. In the full intention-to-treat
      analysis, which included all participants, attendance was found to be almost
      identical across the 3 conditions, around 80%. Some of the women in the
      intervention condition, however, failed to write their plans on the questionnaire
      (10.6% for changing the appointment, 2.1% for travel arrangements, and 21.1% for
      taking time off work) or said that planning was irrelevant to them (2.4% for
      changing the appointment, 1.7% for travel arrangements, and 32.4% for taking time
      off work). A second analysis, of planning time off work, therefore, examined the
      620 respondents in the intervention condition more closely and found that those
      who planned were significantly more likely to attend than those who did not. A
      3rd analysis, excluding the 209 respondents for whom planning time off work was
      irrelevant, revealed that the most likely to plan were those whose initial
      intentions to attend were strong but whose perceptions of control over making the
      necessary arrangements to attend were weak. CONCLUSIONS: Two main implications of
      the findings are discussed: the importance of planning in implementation
      intentions interventions and the validity of the theoretical distinction between
      motivation and volition.

PMID- 16972812
TI  - Weight concerns affect motivation to remain abstinent from smoking postpartum.
AB  - BACKGROUND: Although many women quit smoking during pregnancy, most resume
      smoking postpartum. One factor that may be important in postpartum relapse is a
      pregnant woman's motivation to remain abstinent after delivery. PURPOSE: We
      assessed motivation for postpartum abstinence among pregnant women who had quit
      smoking and examined the relationship of weight concerns and mood to abstinence
      motivation. METHODS: Pregnant former smokers, recruited between February 2000 and
      November 2004, completed assessments of smoking, weight concerns, depressive
      symptoms, and perceived stress. RESULTS: Sixty-five percent were highly motivated
      to remain abstinent postpartum. Women who were and were not motivated were
      similar in age, race, and nicotine dependence. However, motivated women reported
      more stress, greater self-efficacy for weight management, less hunger, and less
      smoking for weight control than did less motivated women. After controlling for
      intention to breast-feed, nicotine dependence, years of smoking, partner smoking,
      and race, self-efficacy for weight control was related to motivation to maintain
      postpartum abstinence. CONCLUSIONS: These data suggest that weight concerns are
      associated with motivation for postpartum smoking abstinence, and interventions
      designed to prevent postpartum smoking relapse may need to target eating, weight,
      and shape concerns.

PMID- 16972813
TI  - Correlates of physical activity among individuals with multiple sclerosis.
AB  - BACKGROUND: There is accumulating evidence that individuals with multiple
      sclerosis (MS) are less physically active than nondiseased populations. One
      method for increasing the level of participation in physical activity among MS
      patients involves the identification of factors that correlate with physical
      activity and that are modifiable by a well-designed intervention. PURPOSE: This
      study adopts a social cognitive perspective and examines self-efficacy,
      enjoyment, social support, and disability as correlates of participation in
      physical activity among individuals with MS. METHODS: We recruited 196
      individuals with a diagnosis of MS from the Midwest region of the United States.
      The participants completed a battery of questionnaires and then wore a belt with
      an accelerometer for a 7-day period. The data were analyzed using covariance
      modeling. RESULTS: Enjoyment (gamma=.38, p<.001), social support (gamma=.15,
      p<.05), and disability (gamma=.18, p<.01) had statistically significant direct
      relations with self-efficacy, and self-efficacy (beta=.29, p<.001) and enjoyment
      (gamma=.28, p<.001) had statistically significant direct relations with physical
      activity. CONCLUSIONS: Future researchers should consider examining self-efficacy
      and enjoyment as possible components of an intervention that is designed to
      increase physical activity participation in MS patients.

PMID- 16972811
TI  - The health effects of at-home written emotional disclosure in fibromyalgia: a
      randomized trial.
AB  - BACKGROUND: The presence and severity of the chronic pain syndrome fibromyalgia
      (FM) is associated with unresolved stress and emotional regulation difficulties.
      Written emotional disclosure is intended to reduce stress and may improve health
      of people with FM. PURPOSE: This study tests the effects of at-home, written
      emotional disclosure about stressful experiences on the health of people with FM
      and uses multiple follow-ups to track the time course of effects of disclosure.
      METHODS: Adults with FM (intention-to-treat, n=83; completers, n=72) were
      randomized to write for 4 days at home about either stressful experiences
      (disclosure group) or neutral time management (control group). Group differences
      in immediate mood effects and changes in health from baseline to 1-month and 3
      month follow-ups were examined. RESULTS: Written disclosure led to an immediate
      increase in negative mood, which did not attenuate across the 4 writing days.
      Repeated-measures analyses from baseline to each follow-up point were conducted
      on both intention-to-treat and completer samples, which showed similar outcomes.
      At 1 month, disclosure led to few health benefits, but control writing led to
      less negative affect and more perceived support than did disclosure. At 3-month
      follow-up, these negative affect and social support effects disappeared, and
      written disclosure led to a greater reduction in global impact, poor sleep,
      health care utilization, and (marginally) physical disability than did control
      writing. Interpretation of these apparent benefits needs to be made cautiously,
      however, because the disclosure group had somewhat poorer health than controls at
      baseline and the control group showed some minor worsening over time.
      CONCLUSIONS: Written emotional disclosure can be conducted at home, and there is
      tentative evidence that disclosure benefits the health of people with FM. The
      benefits, however, may be delayed for several months after writing and may be of
      limited clinical significance.

PMID- 16972814
TI  - Dysfunctional thinking patterns and immigration status as predictors of hearing
      protection device usage.
AB  - BACKGROUND: There is limited research on the role of dysfunctional/irrational
      thinking processes and immigration status on hearing protection device (HPD)
      usage. PURPOSE: The aim of the study is to investigate the effects of low
      frustration tolerance (LFT) and immigration status on HPD usage among employees
      exposed to hazardous industrial noise. METHODS: A total of 117 Israeli-borns and
      80 new immigrants from former Soviet Union completed a questionnaire. The
      association between HPD usage and barriers to action, self-efficacy, and LFT
      (accounting for age, years of exposure, and immigration status) were assessed
      using ordered logistic regression models. RESULTS: LFT was associated negatively
      (adjusted odds ratio [OR]=.25, 95%; confidence interval [CI]=.15-.41) with HPD
      usage. Self-efficacy was a modifier (adjusted OR=1.47, 95%; CI=1.34-1.63): the
      higher the self-efficacy for a given LFT level, the higher the extent of HPD
      usage. Immigration status was not a significant predictor. CONCLUSIONS: HPD usage
      is associated with both rational and irrational motivations. The role of LFT in
      hearing protection should be further investigated.

PMID- 16972816
TI  - The trials of separating bath water from baby: a review and critique of the MMPI
      2 Restructured Clinical Scales.
AB  - I review the development of the new set of MMPI-2 scales, the Restructured
      Clinical (RC) Scales (Tellegen et al., 2003). I identify several conceptual and
      methodological flaws in the construction of these scales, and I discuss the
      influence of a central shortcoming, the use of an atypical and depressively
      biased marker for unwanted ("first-factor") variance and its consequences for the
      RC Scales. I criticize the monograph introducing and describing the development
      of these scales for multiple important omissions. I provide examples of RC Scales
      in which relevant variances were overextracted or underextracted in the process
      of their construction. I introduce and apply the concept of "construct drift" to
      the RC Scales corresponding to the MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen,
      & Kaemmer, 1989) Clinical Scales, Psychasthenia and Hypomania. I conclude that
      the RC Scales are highly redundant with and function as routinely scored Content
      scales and that their designation as Clinical Scales is at best tenuous. I
      present two more appropriate, unbiased markers for the first factor along with
      the description of several nonintrusive strategies for increasing the
      independence of the Clinical Scales without compromising their syndromal
      fidelity.

PMID- 16972817
TI  - The MMPI-2 Restructured Clinical Scales: a paradigmatic shift in scale
      development.
AB  - Tellegen et al. (2003) proposed fundamental changes in MMPI-2 (Butcher,
      Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) scale development by discarding
      empirical scale development in favor of construct validation via Jackson's (1970)
      sequential system of scale development. As a result of their efforts, a general
      distress factor (Demoralization) was identified and 8 Restructured Clinical (RC)
      Scales were developed. Using 7,330 clinical cases from Caldwell's (1997) data
      set, in this study, we sought to cross-validate the MMPI-2 RC Scales. Scale
      homogeneity was confirmed with high alpha coefficients and interitem correlations
      in the expected range. We also achieved a major objective of reducing interscale
      correlations. In replicating Tellegen et al.'s principal components analysis, we
      achieved a high concordance for 6 of the 8 RC Scales. We critically examine these
      results in light of Jackson's construct validation. We discuss the clinical
      usefulness of the MMPI-2 RC Scales within the context of current and future
      research.

PMID- 16972818
TI  - Further evidence on the validity of the MMPI-2 Restructured Clinical (RC) Scales:
      addressing questions raised by Rogers, Sewell, Harrison, and Jordan and Nichols.
AB  - The reviews by Rogers, Sewell, Harrison, and Jordan (2006/this issue), and by
      Nichols (2006/this issue) offer markedly contrasting appraisals of the MMPI-2
      Restructured Clinical (RC) Scales introduced by Tellegen et al. (2003). The one
      common feature is that both reviews draw on the same atypical MMPI-2 (Butcher,
      Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) data set for their empirical
      analyses, with results warranting critical scrutiny. Rogers et al.'s critique
      provides an evaluation of the RC Scales from the perspective of Jackson's (1970)
      method of test development. One significant issue in Rogers et al.'s review
      concerns social desirability, prompting us to clarify our own views on this
      topic. We also highlight and discuss problems associated with Rogers et al.'s use
      of the unrepresentative data set. Nichols's polemical critique neglects empirical
      and theoretical support for demoralization as a central construct and
      misconstrues as "construct drift" the purposeful process of developing the RC
      scales. Nichols's criticisms and proposals overlook requirements for assessing
      syndromes and for construct validation and even rudiments of scale development.
      Our reply incorporates evidence, including new findings, refuting his criticisms
      and confirming that demoralization is a pervasive MMPI dimension, that the RC
      Scales capture the major distinctive features of the original Clinical Scales,
      and that they generate correspondingly meaningful validity patterns.

PMID- 16972819
TI  - Commentary on Rogers, Sewell, Harrison, and Jordan.

PMID- 16972820
TI  - MMPI-2 at the crossroads: aging technology or radical retrofitting?
AB  - Paradigmatic shifts are uncommon in psychological assessment, which is often
      steeped more in tradition than innovative practices. The introduction of the
      Restructured Clinical (RC) Scales by Tellegen et al. (2003) represents a radical
      shift in the development and validation of the MMPI-2 (Butcher, Dahlstrom,
      Graham, Tellegen, & Kaemmer, 1989). In broadening the debate over the merit of
      the RC Scales, in this article, we examine current challenges to MMPI-2
      interpretation including issues with discriminant validity and imprecision (e.g.,
      standard errors of measurement). We evaluate the RC alternative in the context of
      these interpretive challenges. Although we note several improvements, the
      incremental validity for MMPI-2 interpretative statements remains to be
      established. MMPI-2 researchers may wish to test several innovative models for
      their comparative strengths in establishing scale properties and providing
      empirically based interpretations.

PMID- 16972821
TI  - A perspective on the Restructured Clinical (RC) Scale Project.
AB  - The articles in this issue by Nichols (2006/this issue) and Rogers, Sewell,
      Harrison, and Jordan (2006/this issue) provide evaluations and critiques of the
      Restructured Clinical (RC) Scales developed by Tellegen et al. (2003) to reduce
      the high intercorrelations typically found among MMPI-2 (Butcher, Dahlstrom,
      Graham, Tellegen, & Kaemmer, 1989) Basic scales and to correspondingly improve
      the discriminate validity of these scales. This manuscript provides another
      perspective that acknowledges that it would be premature to discontinue the use
      of the standard MMPI-2 basic scales until more research has been accumulated on
      the RC Scales. However, it is also proposed that the RC Scales are an innovative
      and important contribution that holds substantial potential for addressing a
      number of significant limitations in the MMPI-2 and thereby improving the
      assessment of psychopathology with this instrument.

PMID- 16972822
TI  - The deconstruction of the Hy Scale of MMPI-2: failure of RC3 in measuring somatic
      symptom expression.
AB  - The MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) Clinical
      Scales have a long history in psychological assessment. Recently, Tellegen et al.
      (2003) conducted a series of analyses to restructure the scales to reduce what
      they considered to be problems that limit scale functioning. In a critique of the
      Restructured Clinical (RC) Scales published in this issue, Nichols (2006/this
      issue) questions a number of aspects of the approach Tellegen et al. took
      including their theoretical assumptions, methods of analysis, and failures to
      report important information needed for scale evaluation such as relationships
      with existing scales. We concur with many points raised by Nichols. In our
      analysis of the performance of the RC3 scale, we found that it has "drifted" so
      far from the original Hy scale as to be a completely different measure- a scale
      of cynical attitudes that is already well represented in existing MMPI-2
      measures. In this article, we take these concerns a step further and examine the
      history and construct validity of the Hy scale in evaluating the somatic
      expression of problems that the original authors (McKinley & Hathaway, 1944)
      intended. We also include new information from a medical setting, an application
      not represented in Tellegen et al.'s RC Scale monograph. In agreement with Rogers
      et al. (2006/this issue), it is our conclusion that some RC Scales do not
      represent the measurement domain of the original scales and should not be relied
      on for or used to refine traditional interpretation, particularly in medical or
      forensic situations (such as personal injury cases) because of their confusing
      and conflicting results.

PMID- 16972823
TI  - Maximal measurement or meaningful measurement: the interpretive challenges of the
      MMPI-2 Restructured Clinical (RC) Scales.
AB  - The persisting correlations of the Restructured Clinical (RC; Tellegen et al.,
      2003) Scales with independent measures of first-factor variance (A, NEGE) suggest
      that trying to extract demoralization did not work well, and it may not be a
      clinically realistic task. Nichols's (2006/this issue) description of the
      clinical scales as "syndromal" and "multivariate" is seen as accurately
      reflecting their multicore natures so that the emphasis on the extraction of a
      single core unduly distorts the complexity and richness of the scales. Meehl and
      Hathaway (1946) cited factorially derived scales as "maximal" measurement,
      specifically measuring something very well; empirical scales based on criterion
      groups provide "meaningful" measurement as to the similarities of an individual's
      behavior to that of the group. I discuss this narrowness of factorial scales,
      such as the RC Scales, as a limitation of their generalization. I discuss
      problems with interpreting scales on the basis of the face validity of their
      items; assuming that self-perception and self report are accurate is a
      potentially misleading and undependable basis for assessment and intervention. I
      contrast the narrowness of the interpretive specificity of the RC Scales with the
      much broader and surprisingly specific interpretations offered by study of the
      individuals aggregated by the MMPI (Hathaway & McKinley, 1943) and MMPI-2
      (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) code types.

PMID- 16972824
TI  - The MMPI-2 Restructured Clinical (RC) Scales and restraints to innovation, or
      "what have they done to my song?".
AB  - Rogers, Sewell, Harrison, and Jordan (2006/this issue) largely replicate in an
      independent clinical sample the MMPI-2 Restructured Clinical (RC) Scales
      developed by Tellegen et al. (2003). Nichols (2006/this issue) raises numerous
      concerns about the development and utility of the RC Scales, which on close
      appraisal did not change our view that the scales are well conceived and
      potentially valuable to researchers and clinicians alike. We present two case
      studies in which the RC Scales helped clarify complex MMPI-2 (Butcher, Dahlstrom,
      Graham, Tellegen, & Kaemmer, 1989) profiles with multiple elevations on the
      Clinical, Content, Supplementary, and Personality Psychopathology Five (Harkness,
      McNulty, Ben-Porath, & Graham, 2001) scales. When interpretations refined by the
      RC Scales were discussed with the clients, each seemed to feel deeply understood.
      Reservations about instrument innovation can be appreciated as helping to
      counterbalance change and thereby ensure the MMPI-2's successful ongoing
      evolution. We discuss specific ways the MMPI-2 community could avoid polarization
      about the RC Scales.

PMID- 16972825
TI  - Bridging the divide: comments on the Restructured Clinical Scales of the MMPI-2.
AB  - In this comment, I discuss the target articles written by Nichols (2006/this
      issue) and Rogers, Sewell, Harrison, and Jordan (2006/this issue) regarding the
      Restructured Clinical (RC) Scales (Tellegen et al., 2003) of the MMPI-2 (Butcher,
      Dahlstrom, Graham, Tellegen, & Kaemmer, 1989). Both articles provide thoughtful
      discussion of the extent to which the RC Scales achieved the primary goals set
      forth by Tellegen et al., but they set different tones and come to somewhat
      different conclusions. I argue that the initial studies conducted on the RC
      Scales suggest a promising future for them. However, further studies are needed
      to explore the construct validity of the scales, assess their incremental
      validity with respect to other more established MMPI-2 scale sets, and determine
      their interpretive meaning in clinical contexts.

PMID- 16972826
TI  - Syndromal complexity, paradigm shifts, and the future of validation research:
      comments on Nichols and Rogers, Sewell, Harrison, and Jordan.
AB  - In this comment, I address a number of the points raised in the reviews of the
      MMPI-2 Restructured Clinical (RC; Tellegen et al., 2003) Scales by Nichols
      (2006/this issue) and Rogers, Sewell, Harrison, and Jordan (2006/this issue), and
      I advocate for changes in assessment validation research. There is little
      evidence that the "syndromal complexity" Nichols ascribes to the original MMPI-2
      (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) Clinical Scales is worth
      preserving. Although their construction does not constitute the paradigm shift
      claimed by Rogers et al., the RC Scales are promising, psychometrically
      defensible measures of core features of the original MMPI-2 Clinical Scales.
      However, validation of inferences from multiscale inventories such as the MMPI-2
      is limited at present by a disconnection between the integrative manner in which
      MMPI-2 profiles are interpreted and the scale-by-scale nature of most MMPI-2
      validation studies. Q-sort procedures show promise for operationalizing
      integrated MMPI-2 interpretations, with both research and teaching applications.

PMID- 16972827
TI  - Cuffed tracheal tubes in children--things have changed.

PMID- 16972828
TI  - Ultrasonographic guidance in pediatric regional anesthesia Part 1: Theoretical
      background.
AB  - Recent findings support the use of ultrasonographic guidance in pediatric
      regional anesthesia. This review article illustrates basic knowledge in physics
      of ultrasound and ultrasonographic appearance of neuronal structures, which are
      prerequisites for the safe application of this technique in daily clinical
      practice. A critical view on education and ethics in science should emphasize
      future developments in ultrasonography for pediatric regional anesthesia.

PMID- 16972829
TI  - Distraction with a hand-held video game reduces pediatric preoperative anxiety.
AB  - BACKGROUND: Video games have received widespread application in health care for
      distraction and behavior modification therapy. Studies on the effect of cognitive
      distraction during the preoperative period are lacking. We evaluated the efficacy
      of an interactive distraction, a hand-held video game (VG) in reducing
      preoperative anxiety in children. METHODS: In a randomized, prospective study of
      112 children aged 4-12 years undergoing outpatient surgery, anxiety was assessed
      after admission and again at mask induction of anesthesia, using the modified
      Yale Preoperative Anxiety Scale (mYPAS). Postoperative behavior changes were
      assessed with the Posthospital Behavior Questionnaire (PHBQ). Patients were
      randomly assigned to three groups: parent presence (PP), PP+a hand-held VG, and
      PP+0.5 mg.kg-1 oral midazolam (M) given>20 min prior to entering the operating
      room. RESULTS: There was a statistically significant increase in anxiety (P<0.01)
      in groups M and PP at induction of anesthesia compared with baseline, but not in
      VG group. VG patients demonstrated a decrease in anxiety from baseline (median
      change in mYPAS -3), the difference compared with PP (+11.8) was significant
      (P=0.04). The change in anxiety in the M group (+7.3) was not statistically
      different from other groups. Sixty-three percent of patients in VG group had no
      change or decrease in anxiety after treatment, compared with 26% in M group and
      28% in PP group (P=0.01). There was no difference in anxiety changes between
      female and male patients. CONCLUSIONS: A hand-held VG can be offered to most
      children as a low cost, easy to implement, portable, and effective method to
      reduce anxiety in the preoperative area and during induction of anesthesia.
      Distraction in a pleasurable and familiar activity provides anxiety relief,
      probably through cognitive and motor absorption.

PMID- 16972830
TI  - Training for neonatal resuscitation with the laryngeal mask airway: a comparison
      of the LMA-ProSeal and the LMA-Classic in an airway management manikin.
AB  - BACKGROUND: Neonatal resuscitation is a mandatory skill for healthcare
      professionals involved in maternity suites. For ethical reasons, it is impossible
      to teach and practice airway management skills on neonates, and manikins are used
      for this purpose. The Classic Laryngeal Mask Airway TM (cLMA) is accepted as an
      effective device for airway management during neonatal resuscitation. A neonatal
      size of the LMA-ProSeal (PLMA) was recently produced, but there are no
      comparative data on its performance. We describe the comparison of the
      performances of the neonatal cLMA and the neonatal PLMA when used by different
      healthcare professionals in a dedicated airway management manikin. METHODS:
      Thirty-five healthcare professionals, were given a brief description of the two
      devices followed by 15 min of supervised insertions on a single manikin. Every
      trainee was then instructed to insert both devices four times. The time from
      insertion to the first inflation of the artificial lungs (insertion time, IT) was
      recorded by a single unblinded observer. RESULTS: No failed insertions were
      recorded. The success rates of the first attempt were higher with the PLMA than
      the cLMA (97.1% vs 92.1%; P<0.01). The mean+/-sd (range) IT was significantly
      lower with the cLMA compared with the PLMA [10.47+/-2.85 (6-22) s vs 11.34+/-2.5
      (7-18) s; P<0.01]. The mean+/-sd (range) IT of the cLMA was 12.31+/-3.54 (7-22) s
      for the first positioning and 9.2+/-2.34 (6-16) s for the fourth (P<0.01). The
      mean+/-sd (range) IT of the PLMA was 12.71+/-2.52 (8-18) s for the first
      positioning and 10.17+/-2.28 (7-14) s for the fourth (P<0.01). There were no
      significant differences among groups. CONCLUSIONS: Both LMAs are easy to insert
      by different delivery-room workers. PLMA (with the introducer tool) has a higher
      success rate at first attempt than cLMA. Manikin ventilation was established
      equally without difference in performance among doctors, nurses, midwives. A
      brief manikin-training reduces the IT significantly. The longer IT of PLMA vs
      cLMA is without clinical relevance.

PMID- 16972831
TI  - Anesthesia for pediatric gastroscopy: a study comparing the ProSeal laryngeal
      mask airway with nasal cannulae.
AB  - BACKGROUND: We tested the hypothesis that pediatric gastroscopy is more
      successful using the ProSeal laryngeal mask airway with the drain tube as a
      conduit to the stomach (ProSeal LMA group) than using nasal cannulae with
      conventional oral access to the stomach (NC group). METHODS: Sixty children were
      consecutively and randomly allocated into each group. Patients breathed
      spontaneously and were given sevoflurane/air/oxygen mixture with propofol 1 mg.kg
      1 boluses, as required. Anesthesia was provided by experienced users of both
      techniques. The following data were collected by an unblinded observer: operation
      and anesthesia times; cardiorespiratory data; adverse events; and recovery
      scores. In addition, the surgeon scored the ease of performing the procedure.
      RESULTS: The mean (range) age and weight was 74 (24-144) months and 26 (10-61)
      kg. Operation (15 min vs 24 min, P<0.0001) and anesthesia (22 min vs 37 min,
      P<0.0001) times were shorter in the ProSeal LMA group, but propofol bolus
      requirements per unit time were similar. Oxygen saturation was higher in the
      ProSeal LMA group (100% vs 94%, P<0.0006), but other cardiorespiratory variables
      were similar. There were no differences in the ease of performing the procedure.
      Hypoxia occurred more frequently in the NC group (20% vs 0%). Recovery scores
      were similar. CONCLUSIONS: We conclude that pediatric gastroscopy is quicker and
      has fewer airway complications when performed through the ProSeal LMA than using
      nasal cannulae and a conventional approach by experienced users.

PMID- 16972832
TI  - The effect of capsicum plaster in pain after inguinal hernia repair in children.
AB  - BACKGROUND: Capsicum plaster at a classical Chinese acupoint is an alternative to
      acupuncture, which has been used as a supplemental therapy to opioid analgesics
      for pain control during the postoperative period. We investigated the
      postoperative analgesic efficacy of capsicum plaster at Zusanli (ST-36) points
      after pediatric hernia repair. METHODS: This double-blind, sham-controlled study
      was designed in 108 children, aged 4 month to 9 year, undergoing unilateral
      hernia repair, and was randomly assigned to three treatment regimens: group
      Zusanli (Z)=capsicum plaster at Zusanli acupoints and placebo tape on the
      shoulder as a nonacupoint, group Sham (S)=capsicum plaster on the shoulders and
      placebo tape at Zusanli acupoints, and group control (C)=placebo tape at Zusanli
      acupoints and on the shoulder. The postoperative pain scores and analgesic
      requirements during 24 h postoperatively were assessed. RESULTS: Total meperidine
      consumption was significantly lower in group Z (0.87+/-0.35 mg.kg-1) compared
      with group C (1.27+/-0.41 mg.kg-1) and S (1.22+/-0.45 mg.kg-1) (P<0.001). The
      pain scores on both the objective pain scale (OPS) and the Children Hospital of
      Ontario Pain Scale (CHEOPS), were significantly lower in group Z compared with
      the other groups at 6 and 24 h postoperatively, but not at the 10 min and 1 h
      postoperative time periods. CONCLUSIONS: Placement of capsicum plaster at the
      Zusanli points reduces pain and postoperative opioid consumption in children
      undergoing inguinal hernia repair, but not in the first six postoperative hours.

PMID- 16972833
TI  - Recombinant activated factor VII (rFVIIa) treatment in infants with hemorrhage.
AB  - BACKGROUND: Recombinant activated factor VII (rFVIIa) is approved by the FDA for
      the treatment of bleeding episodes in patients with hemophilia A or B with
      inhibitors to factor VIII or factor IX. In addition to the FDA-approved
      indications, rFVIIa has been anecdotally reported effective for profound bleeding
      episodes in adult patients without hemophilia, and proven beneficial for adults
      with intracranial hemorrhage. In the pediatric literature, case reports have been
      made with apparent clinical improvement seen after the use of rFVIIa for acute
      life-threatening bleeding; however, there are limited data regarding its use in
      infants<4 months of age. We report our experience with rFVIIa in nine infants
      with severe hemorrhage of diverse etiologies. METHODS: This case series of
      infants under 4 months with coagulopathy and bleeding treated with rFVIIa was
      collected from two institutions. We report the age, weight and pre-rFVIIa
      laboratory values of the patients as well as the clinical scenario and outcomes.
      RESULTS: The nine infants all suffered acute life-threatening hemorrhage. Two
      patients were postoperative from cardiac surgery, two with Vitamin K deficiency
      and intracranial hemorrhage, three with suspected necrotizing enterocolitis and
      abdominal hemorrhage, and two with pulmonary hemorrhage. The patients ranged in
      age from 2 days to 4 months, (average age 1 month and average weight 3.3+/-1.0
      kg). Seven of the nine patients had frozen plasma, cryoprecipitate, or platelet
      administration in failed attempts to correct the coagulation defect prior to
      receiving rFVIIa. The dose range used in this series was 90-100 microg.kg-1, with
      90 microg.kg-1 being the most commonly used dose. The average pre-rFVIIa INR was
      8.7+/-5.1. Four patients had an immeasurably high INR. All patients had clinical
      resolution of bleeding after receiving rFVIIa, and seven of nine patients
      survived. CONCLUSIONS: rFVIIa is a powerful hemostatic drug whose mechanism of
      action provides a theoretical specificity to sites of tissue injury. In addition
      to its FDA-approved uses in hemophiliac patients, this drug has a potential role
      in the treatment of life-threatening hemorrhage from multiple causes.

PMID- 16972834
TI  - Does tramadol wound infiltration offer an advantage over bupivacaine for
      postoperative analgesia in children following herniotomy?
AB  - BACKGROUND: It has been demonstrated that tramadol is an effective analgesic. We
      aimed to compare postoperative analgesic effects of wound infiltration with
      tramadol (T) or bupivacaine (B) and intramuscular tramadol (I) after herniotomy
      in children. METHODS: In this study, 75 children were randomly assigned to group
      T, group B and group I. Wound infiltration was performed to the patients in group
      T (2 mg.kg-1 tramadol in 0.2 ml.kg-1 saline) and group B (0.2 ml.kg-1 0.25%
      bupivacaine) into the surgical incision. Twenty minutes before the end of the
      surgery 2 mg.kg-1 tramadol was injected i.m. in group I. Faces pain scale was
      used for assessing pain severity. Patients with pain score>2 were treated with
      paracetamol. The frequency of side effects and analgesic use were recorded.
      Patients were discharged on the next day. RESULTS: No side effects were recorded
      in any group. The pain scores of the patients at the first, fourth and eighth
      hours were significantly higher in group B and group I than group T (P<0.05). The
      pain scores of the patients at the first hour were significantly higher in group
      I compared with group B (P<0.05). Average time to first analgesic requirement was
      significantly longer in group T (6.72+/-4.09 h after herniotomy than both group I
      (4.49+/-3.9 h) and group B (6.04+/-3.7 h) (P<0.05). CONCLUSIONS: Wound
      infiltration with tramadol may be a good choice for postoperative analgesia in
      children having inguinal herniotomy.

PMID- 16972835
TI  - Postoperative sleep disturbance in pediatric patients using patient-controlled
      devices (PCA).
AB  - BACKGROUND: Sleep disturbance has not been well quantified in pediatric
      postoperative management, yet has broad implications in pain management as well
      as upon the physical and psychological well-being of the young patient admitted
      for surgery. We aimed to describe sleep disturbance in this population using
      patient-controlled analgesia (PCA) and then identify the predictors of disturbed
      sleep. METHODS: A retrospective audit and analysis of sleep disturbance in
      postoperative pediatric patients using PCA devices were performed in a
      postoperative surgical ward population of a major tertiary referral center. PCA
      presses were used as a proxy measure of sleep. The description of the sleep
      disturbance included an unadjusted and adjusted analysis of the proposed
      predictors of sleep disturbance: age, sex, nature of presentation, operation
      type, PCA opioid type, presence of background infusion, postoperative night
      number, and adjuvant medication. All data were entered into an access database
      developed for the audit and analyzed using stata 8.0. RESULTS: The first 126
      children prescribed PCA devices in the year 2004 were audited. One-third of
      patients in the population prescribed PCA experienced sleep disturbance. Observed
      predictors of sleep disturbance include older children (OR: 0.86, P=0.001) and
      those receiving a background infusion (OR: 0.19, P=0.002). Other predictors were
      not significant. CONCLUSIONS: Sleep disruption is common in children-prescribed
      PCA opioid analgesia. Older children and those receiving a background infusion
      were observed to experience less sleep. Other proposed predictors were not found
      to be reliable. Further investigation into the predictors of disturbed sleep in
      the postoperative patient is warranted.

PMID- 16972836
TI  - Severe withdrawal syndrome in three newborns subjected to continuous opioid
      infusion and seizure activity dependent on brain hypoxia--ischemia. A possible
      link.
AB  - BACKGROUND: The aim of this investigation was to verify whether brain hypoxia
      represented a risk factor for the occurrence and severity of opioid abstinence
      syndrome. METHODS: Three newborns who manifested seizure activity as a result of
      hypoxia, focal brain ischemia, and hypoxia and sepsis, respectively, were
      compared with 17 neonates who suffered from hypoxia without developing seizure
      activity. RESULTS: The first three neonates suffered a severe withdrawal syndrome
      (a rating on the neonatal abstinence score>17), the others did not. CONCLUSIONS:
      It is hypothesized that brain hypoxia facilitated the occurrence and severity of
      the withdrawal syndrome because some key neurochemical processes (such as N
      methyl-D-aspartate activation, protein kinase C activation and nitric oxide
      production) are common to both phenomena.

PMID- 16972837
TI  - The pattern of intravenous drug administration during the transfer of critically
      ill children by a specialist transport team.
AB  - BACKGROUND: There are few published data on the patterns of intravenous drug
      administration by specialist pediatric intensive care unit (PICU) transport teams
      during the transfer of critically ill children between hospitals. METHODS: A
      retrospective review of retrieval documentation was undertaken for all patients
      transported by the Royal Manchester Children's Hospital PICU transport team over
      a period of 1 year. RESULTS: A total of 257 patients were transported during the
      study period, 82 patients (32%) were excluded owing to incomplete or absent
      documentation, leaving a sample of 175 available for analysis. Intravenous drugs
      were administered to 168 of these patients (96%). In total, 38 different drugs
      were administered. The four most commonly administered drugs were midazolam (130
      patients), morphine (129 patients), atracurium (108 patients), and heparin (53
      patients). Ten drugs accounted for 90% of all prescription episodes (total number
      of infusions and bolus doses administered), whilst 16 drugs were prescribed only
      once. The mean number of drugs administered per patient was 3.25 with a mean of
      1.96 drug infusions and 1.29 bolus drugs administered per patient. CONCLUSIONS: A
      relatively small number of drugs are used frequently during the retrieval of
      critically ill children, but the total range of drugs that are used is large.
      This has implications for the rational carriage of drugs by PICU transport teams,
      the potential for drug errors and also for the development of advanced nurse
      practitioners whose prescribing-like activities may depend on the development of
      Patient Group Directions.

PMID- 16972838
TI  - Traumatic tracheoesophageal fistula in a 5-year old.
AB  - Tracheosophageal fistula following blunt trauma is rare and diagnosis and
      management can be difficult. All reported cases have involved victims above 12
      years of age. Here we report the anesthesia management, for surgery, of a
      tracheoesophageal fistula caused by blunt trauma in a 5-year-old boy.

PMID- 16972839
TI  - Abdominal pain related to mitochondrial neurogastrointestinal encephalomyopathy
      syndrome may benefit from splanchnic nerve blockade.
AB  - Patients diagnosed with abdominal pain related to mitochondrial
      neurogastrointestinal encephalopathy (MNGIE) may benefit from splanchnic nerve
      blockade. MNGIE, varying in age of onset and rate of progression, is caused by
      loss of function mutation in thymidine phosphorylase gene. Gastrointestinal
      dysmotility, pseudo-obstruction and demyelinating sensorimotor peripheral
      neuropathy (stocking-glove sensory loss, absent tendon reflexes, distal limb
      weakness, and wasting) are the most prominent manifestations. Patients usually
      die in early adulthood (mean 37.6 years; range 26-58 years). We report a case of
      an 18-year-old patient with MNGIE. Our patient's abdominal pain was relieved
      after splanchnic nerve blockade.

PMID- 16972840
TI  - Repeat episodes of severe muscle rigidity in a child receiving sevoflurane.
AB  - We report on a patient who developed two episodes of severe muscle rigidity,
      increased endtidal CO2 and increased creatine phosphate kinase associated with
      sevoflurane anesthesia. Dysrhythmias and hyperthermia were not observed and
      dantrolene was not administered. Genetic testing for the 17 known mutations
      associated with malignant hyperthermia (MH) was negative. Although we cannot rule
      out MH or other neuromuscular diseases we suggest that this rare event may be a
      direct effect of sevoflurane.

PMID- 16972841
TI  - Anesthesia in a child with newly diagnosed Hypertrophic Cardiomyopathy.
AB  - We report the initial resuscitation and subsequent management of a child with
      newly diagnosed Hypertrophic Cardiomyopathy (HCM), which presented as an out of
      hospital cardiac arrest. HCM is an autosomal dominant condition that is
      uncommonly encountered in the pediatric setting and is an important cause of
      sudden death. Here, we describe the safe use of an anesthetic technique for
      insertion of an implantable cardioverter-defibrillator that ensured strict
      hemodynamic stability and modest bradycardia.

PMID- 16972842
TI  - Iliac compartment block following ilioinguinal iliohypogastric nerve block.
AB  - Transient femoral nerve palsy is a known complication associated with
      percutaneous ilioinguinal iliohypogastric nerve block. Excess volume and higher
      concentrations of local anesthetic have been implicated for transient femoral
      nerve palsy. We encountered partial iliac compartment block involving lateral
      cutaneous nerve of the thigh and femoral nerve with a lower concentration (0.25%)
      of bupivacaine administered in the smallest indicated volume of 0.25 ml.kg-1
      using a double-shot technique.

PMID- 16972843
TI  - Management of right ventricular outflow tract reactivity following pulmonary
      valve dilatation under general anesthesia: experience of a medical mission.
AB  - During a recent volunteer medical mission to the Dominican Republic, we
      administered anesthesia to a child with severe pulmonary valvular stenosis and
      suprasystemic right ventricular pressure. This patient underwent a balloon
      pulmonary valvuloplasty but then developed worsening right ventricular outflow
      tract obstruction that required immediate therapy to prevent a low cardiac output
      state. As the development of hyperdynamic right ventricular outflow tract
      obstruction cannot be predicted, we emphasize the need for preemptive hydration
      and beta-blockade therapy prior to balloon dilatation.

PMID- 16972844
TI  - Anesthetic implications of the catastrophic antiphospholipid syndrome.
AB  - The antiphospholipid antibody syndrome (or the anticardiolipin antibody syndrome)
      is characterized by the presence of autoantibodies. Its major association is with
      systemic lupus erythematosus. 'Catastrophic' antiphospholipid syndrome (CAPS) is
      defined as an accelerated form of APS usually resulting in multiorgan failure and
      can be precipitated by surgery. We present the case of a 12-year-old male child
      who presented for enucleation of his left eye for fungal endopthalmitis. This
      patient had a history of CAPS 2 months before surgery with myocardial,
      gastrointestinal, renal and laryngeal involvement that improved on aggressive
      treatment and was subsequently managed on an outpatient basis for 2 months before
      presenting for enucleation. To the best of our knowledge, this is the first case
      of CAPS in a child reported in the anesthetic literature. Further aspects of this
      puzzling condition and its anesthesia implications are discussed.

PMID- 16972845
TI  - An unusual complication of dorsal penile nerve block for circumcision.

PMID- 16972846
TI  - Total contralateral atelectasis following rigid bronchoscopy in a child with
      scarf pin aspiration.

PMID- 16972847
TI  - Prevention of burns caused by transillumination for peripheral venous access in
      neonates.

PMID- 16972848
TI  - Fasciotomy following intravenous fluid infiltration.

PMID- 16972849
TI  - Temperature probe in distal esophagus: a cause of accidental extubation in an
      infant.

PMID- 16972850
TI  - Hyperthermia during surgery with TissueLink.

PMID- 16972851
TI  - An evaluation of pain, postoperative nausea and vomiting following the
      introduction of guidelines for tonsillectomy.

PMID- 16972856
TI  - Prioritising for fertility treatments--should a high BMI exclude treatment?

PMID- 16972857
TI  - Obesity, waist-hip ratio and hunter-gatherers.
AB  - Obesity is a rapidly growing global problem. It is not simply the result of
      eating too much, and not all types of obesity have the same significance. Obesity
      is in part genetic, and one particularly important genetic type of obesity is the
      tendency to 'truncal obesity',-that is, a raised waist-to-hip ratio. Such obesity
      is powerfully associated not only with a tendency to diabetes, but also to
      cardiovascular disease, ('Syndrome X'). Interestingly, this is the type of
      obesity seen in every hunter-gatherer (HG) population around the globe. Such
      people are intolerant of carbohydrate, especially refined carbohydrate,
      especially in the excessive amounts typically consumed in affluent societies. In
      such pure HG communities, rates of diabetes can be as high as 50%, when the
      'Western' lifestyle is adopted. Many of us, however, share some of their genes
      and their carbohydrate intolerance-perhaps as many as 20 or 30% of the world's
      population. Pregnancy can uncover this characteristic, and obesity and glucose
      intolerance in pregnancy are rapidly burgeoning problems. Quite contrary to the
      common nutritional dogma of encouraging regular carbohydrates, it is suggested
      that pregnant women with a high waist-to-hip ratio should be strongly advised to
      adhere to a low-glycaemic-index diet. Additionally, many dietary interventions,
      some of them derived from observation of HG populations, are of proven benefit in
      reducing the expression of glucose intolerance and may well help in tackling the
      obesity epidemic.

PMID- 16972858
TI  - Maternal obesity in pregnancy: Is it time for meaningful research to inform
      preventive and management strategies?
AB  - The growing epidemic of obesity in our society has become a major public health
      issue, with serious social and psychological consequences in addition to the
      physical health implications. Obesity has reached epidemic proportions globally
      with a similar rise in prevalence among women in the reproductive age group. This
      has critical consequences for fetal and maternal health in the antepartum,
      intrapartum and postpartum periods. The aims of this study were to summarise the
      implications of maternal obesity on maternal, fetal and neonatal health and to
      recommend good practice guidelines on the management of this problem. The authors
      highlight the need for good quality interventional research on maternal obesity
      while identifying avenues with potential scope for future research in this
      context.

PMID- 16972859
TI  - Operating on the obese woman--A review.
AB  - In this review the authors recognise the growing contribution of obesity to
      problems in obstetrics and gynaecology. They then focus on methods to reduce
      complications in intrapartum and gynaecological care particularly in relation to
      operating on the obese woman. Strategies to reduce surgical morbidity are
      discussed including consideration of the site of incision, asepsis and reduction
      in postoperative complications.

PMID- 16972860
TI  - Linear association between maternal pre-pregnancy body mass index and risk of
      caesarean section in term deliveries.
AB  - OBJECTIVE: Maternal obesity is a well-known risk factor for caesarean delivery.
      The aim of this study is to determine whether all the spectrum of pre-pregnancy
      maternal corpulence (body mass index [BMI]) is associated with the risk of
      caesarean delivery. DESIGN: Observational study over 4.5 years (2001-05).
      SETTING: Groupe Hospitalier Sud-Reunion's maternity (island of La Reunion, French
      overseas department, Indian Ocean). POPULATION: All consecutive singleton live
      births having delivered at the maternity. METHODS: Data have been analysed
      according to different risk factors. Maternal corpulence has been defined as the
      maternal pre-pregnancy weight. BMIs have been studied by multiples of 5 kg/m2
      from 10-14.9 kg/m2 to 40-44.9 kg/m2. MAIN OUTCOME MEASURE: Rate of caesarean
      section. RESULTS: There were 17 462 singleton live births during the period, of
      which 16 952 (97.1% of the total) pre-pregnancy BMIs have been determined. There
      is a linear association (chi 2 for linear trend, P < 0.001) between maternal
      corpulence and risk of caesarean deliveries, the leanest mothers having the best
      rate of vaginal delivery. This linear association exists in a model controlling
      for diagnosis of gestational diabetes, term deliveries (> or =37 weeks), very
      short maternal height (<1.50 m), primiparity and maternal age > or = 35 years
      (adjusted chi 2, P < 0.001). CONCLUSION: There is a significant linear
      association between pre-pregnancy maternal corpulence and risk of caesarean
      deliveries in pregnancies at term. The authors discuss several interpretations
      including the adaptability of fetal birthweights to maternal corpulence and the
      concept of soft-tissue dystocia.

PMID- 16972861
TI  - Audit of the influence of body mass index on the performance of epidural
      analgesia in labour and the subsequent mode of delivery.
AB  - OBJECTIVE: To assess the influence of body mass index (BMI) on the performance of
      epidural analgesia in labour and the subsequent mode of delivery. DESIGN: A
      retrospective audit of prospectively collected quality assurance data. SETTING:
      The delivery suite of Leeds General Infirmary, Leeds, UK. This is a 4500-delivery
      teaching hospital unit. POPULATION: All women receiving epidural analgesia during
      labour in our unit between April 1997 and December 2005. METHODS: Epidural
      recipients were divided into BMI groups according to World Health Organization
      (WHO) categories and compared for indices of epidural performance and mode of
      delivery. MAIN OUTCOME MEASURES: Midwife and patient satisfaction scores with
      epidural analgesia, epidural resite rates, and mode of delivery. RESULTS: Data
      from 13 299 epidural recipients were analysed. Using WHO definitions, 22.8% were
      of normal body mass, 41.9% were overweight, 31.9% obese, and 3.4% morbidly obese.
      Epidurals were more likely to fail as BMI increased, as judged by midwife
      satisfaction scores (P < 0.001) and epidural resite rates (P < 0.01). This trend
      was not seen for maternal satisfaction scores using the WHO BMI categories.
      However, if women with BMI below 30 kg/m2 were grouped together, a significant
      trend was found (P < 0.01). BMI had no influence on vaginal instrumental
      deliveries, but caesarean section rates rose from 11.5% in women of normal BMI to
      29.2% in the morbidly obese women (P < 0.001). CONCLUSIONS: Obesity increases the
      incidence of analgesic failure and the need for resite of epidurals. The
      caesarean section rate among epidural recipients increases dramatically as BMI
      rises.

PMID- 16972862
TI  - Metabolic and polycystic ovary syndromes in indigenous South Asian women with
      previous gestational diabetes mellitus.
AB  - OBJECTIVE: To determine the risk of metabolic syndrome (MS) and polycystic ovary
      syndrome (PCOS) in a cohort of indigenous South Asian women with a recent history
      of gestational diabetes mellitus (GDM). DESIGN: Case-control study. SETTING:
      Department of Obstetrics & Gynaecology, University of Colombo, Sri Lanka. SAMPLE:
      Two hundred and seventy-four indigenous Sri Lankan women with previous GDM and
      168 ethnically matched controls. Of these, 147 with previous GDM and 67 controls
      not taking hormonal contraception participated in an in-depth endocrine study.
      METHODS: Assessing the prevalence of MS and PCOS based on clinical features,
      biochemistry and ovarian ultrasound examination at 3 years postpartum. MAIN
      OUTCOME MEASURES: Prevalence of MS and PCOS. RESULTS: Women with previous GDM and
      controls were studied at a mean (range) of 34.6 (13.4-84.1) and 46.5 (17.5-78)
      months postpartum, respectively. Those with previous GDM had a larger mean +/-
      95% confidence interval waist circumference (90.9 +/- 1.3 versus 81.2 +/- 2.8 cm,
      P = 0.0004) and were more likely to have hypertension (17.6 versus 7.4%, P =
      0.001), glucose intolerance (51.7 versus 10.4%, P = 0.00001),
      hypertriglyceridaemia (16.3 versus 5.9%, P = 0.02) and a lower level of high
      density lipoprotein (70 versus 56.7%, P = 0.04) than the controls. Of the women
      who had GDM, 72 (49%) had MS, 86 (58.5%) had polycystic ovaries and 59 (40%) had
      PCOS, significantly more than the control women-4 (6%), 9 (13%) and 2 (3%),
      respectively (P = 0.00001). CONCLUSIONS: The prevalence of MS and PCOS in
      indigenous Sri Lankan women 3 years postpartum is significantly higher in those
      with previous GDM compared with ethnically matched controls. This confirms an
      association between GDM and subsequent PCOS and MS.

PMID- 16972863
TI  - PCOS according to the Rotterdam consensus criteria: Change in prevalence among
      WHO-II anovulation and association with metabolic factors.
AB  - OBJECTIVE: The current report aims to compare the prevalence of polycystic ovary
      syndrome (PCOS) diagnosed according to the new Rotterdam criteria (Rott-PCOS)
      versus the previous criteria as formulated by the National Institutes of Health
      (NIH) (NIH-PCOS) in women with normogonadotropic (WHO-II) anovulation and assess
      the frequency of obesity and related factors determined in these women. DESIGN:
      Cohort study based on large anovulation screening database. SETTING: Two large
      tertiary referral centres for reproductive medicine. POPULATION: WHO-II
      normogonadotropic, anovulatory, infertility cases. METHODS: WHO-II cases were
      extracted from the screening database and classified according to both the
      Rotterdam and NIH criteria for PCOS. Within these two classes, the prevalence of
      obesity, hyperglycaemia and insulin resistance was assessed and compared and
      their relation to the difference in diagnostic criteria applied was analysed.
      MAIN OUTCOME MEASURES: Prevalence of diagnosis PCOS in the WHO-II anovulation
      group. Prevalence of obesity, hyperglycaemia and insulin resistance in the two
      diagnostic classes. RESULTS: The Rott-PCOS group appeared to be more than 1.5
      times larger than the group classified as NIH-PCOS (91 versus 55% of the WHO-II
      cohort). Especially, women with ovarian dysfunction and polycystic ovaries at
      ultrasound scan, but without hyperandrogenism, were added to the PCOS diagnostic
      group. The Rott-PCOS exhibited a lower frequency of obesity, hyperglycaemia and
      insulin resistance compared with the NIH-PCOS group. Obese women in the Rott-PCOS
      group without androgen excess had a different metabolic profile compared with
      obese women in the NIH-PCOS group, with lower rates of hyperglycaemia and
      hyperinsulinism, despite comparable distributions of body weight. CONCLUSION: The
      present findings indicate that with the new Rotterdam consensus criteria,
      oligo/anovulatory women with less severe metabolic derangement will be added to
      the heterogeneous group of women with PCOS.

PMID- 16972865
TI  - Phototropin involvement in the expression of genes encoding chlorophyll and
      carotenoid biosynthesis enzymes and LHC apoproteins in Chlamydomonas reinhardtii.
AB  - Phototropin (PHOT) is a photoreceptor involved in a variety of blue-light
      elicited physiological processes including phototropism, chloroplast movement and
      stomatal opening in plants. The work presented here tests whether PHOT is
      involved in expression of light-regulated genes in Chlamydomonas reinhardtii.
      When C. reinhardtii was transferred from the dark to very low-fluence rate white
      light, there was a substantial increase in the level of transcripts encoding
      glutamate-1-semialdehyde aminotransferase (GSAT), phytoene desaturase (PDS) and
      light-harvesting polypeptides (e.g. LHCBM6). Increased levels of these
      transcripts were also elicited by low-intensity blue light, and this blue-light
      stimulation was suppressed in three different RNAi strains that synthesize low
      levels of PHOT. The levels of GSAT and LHCBM6 transcripts also increased
      following exposure of algal cells to low-intensity red light (RL). The red-light
      dependent increase in transcript abundance was not affected by the electron
      transport inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea, implying that the
      influence of RL on transcript accumulation was not controlled by cytoplasmic
      redox conditions, and that a red-light photoreceptor(s) may be involved in
      regulating the levels of transcripts from specific photosynthesis-related genes
      in C. reinhardtii. Interestingly, elevated GSAT and LHCBM6 transcript levels in
      RL were significantly reduced in the PHOT RNAi strains, which raises the
      possibility of co-action between blue and RL signaling pathways. Microarray
      experiments indicated that the levels of several transcripts for photosystem (PS)
      I and II polypeptides were also modulated by PHOT. These data suggest that, in C.
      reinhardtii, (i) PHOT is involved in blue-light-mediated changes in transcript
      accumulation, (ii) synchronization of the synthesis of chlorophylls (Chl),
      carotenoids, Chl-binding proteins and other components of the photosynthetic
      apparatus is achieved, at least in part, through PHOT-mediated signaling, and
      (iii) a red-light photoreceptor can also influence levels of certain transcripts
      associated with photosynthetic function, although its action requires normal
      levels of PHOT.

PMID- 16972866
TI  - FtsH11 protease plays a critical role in Arabidopsis thermotolerance.
AB  - Plants, as sessile organisms, employ multiple mechanisms to adapt to the seasonal
      and daily temperature fluctuations associated with their habitats. Here, we
      provide genetic and physiological evidence that the FtsH11 protease of
      Arabidopsis contributes to the overall tolerance of the plant to elevated
      temperatures. To identify the various mechanisms of thermotolerance in plants, we
      isolated a series of Arabidopsis thaliana thermo-sensitive mutants (atts) that
      fail to acquire thermotolerance after pre-conditioning at 38 degrees C. Two
      allelic mutants, atts244 and atts405, were found to be both highly susceptible to
      moderately elevated temperatures and defective in acquired thermotolerance. The
      growth and development of the mutant plants at all stages examined were arrested
      after exposure to temperatures above 30 degrees C, which are permissive
      conditions for wild-type plants. The affected gene in atts244 was identified
      through map-based cloning and encodes a chloroplast targeted FtsH protease,
      FtsH11. The Arabidopsis genome contains 12 predicted FtsH protease genes, with
      all previously characterized FtsH genes playing roles in the alleviation of light
      stress through the degradation of unassembled thylakoid membrane proteins and
      photodamaged photosystem II D1 protein. Photosynthetic capability, as measured by
      chlorophyll content (chl a/b ratios) and PSII quantum yield, is greatly reduced
      in the leaves of FtsH11 mutants when exposed to the moderately high temperature
      of 30 degrees C. Under high light conditions, however, FtsH11 mutants and wild
      type plants showed no significant difference in photosynthesis capacity. Our
      results support a direct role for the A. thaliana FtsH11-encoded protease in
      thermotolerance, a function previously reported for bacterial and yeast FtsH
      proteases but not for those from plants.

PMID- 16972867
TI  - Biosynthesis and secretion of mugineic acid family phytosiderophores in zinc
      deficient barley.
AB  - Mugineic acid family phytosiderophores (MAs) are metal chelators that are
      produced in graminaceous plants in response to iron (Fe) deficiency, but current
      evidence regarding secretion of MAs during zinc (Zn) deficiency is contradictory.
      Our studies using HPLC analysis showed that Zn deficiency induces the synthesis
      and secretion of MAs in barley plants. The levels of the HvNAS1, HvNAAT-A, HvNAAT
      B, HvIDS2 and HvIDS3 transcripts, which encode the enzymes involved in the
      synthesis of MAs, were increased in Zn-deficient roots. Studies of the genes
      involved in the methionine cycle using microarray analysis showed that the
      transcripts of these genes were increased in both Zn-deficient and Fe-deficient
      barley roots, probably allowing the plant to meet its demand for methionine, a
      precursor in the synthesis of MAs. In addition, HvNAAT-B transcripts were
      detected in Zn-deficient shoots, but not in those that were deficient in Fe.
      Increased synthesis of MAs in Zn-deficient barley was not due to a deficiency of
      Fe, because Zn-deficient barley accumulated more Fe than did the control plants,
      ferritin transcripts were increased in Zn-deficient plants, and Zn deficiency
      promoted Fe transport from root to shoot. Moreover, analysis using the positron
      emitting tracer imaging system (PETIS) confirmed that more 62Zn(II)-MAs than
      62Zn2+ were absorbed by the roots of Zn-deficient barley plants. These data
      suggest that the increased biosynthesis and secretion of MAs arising from a
      shortage of Zn are not due to an induced Fe deficiency, and that secreted MAs are
      effective in absorbing Zn from the soil.

PMID- 16972868
TI  - Multi-site genetic modulation of monolignol biosynthesis suggests new routes for
      formation of syringyl lignin and wall-bound ferulic acid in alfalfa (Medicago
      sativa L.).
AB  - Genes encoding seven enzymes of the monolignol pathway were independently
      downregulated in alfalfa (Medicago sativa) using antisense and/or RNA
      interference. In each case, total flux into lignin was reduced, with the largest
      effects arising from the downregulation of earlier enzymes in the pathway. The
      downregulation of l-phenylalanine ammonia-lyase, 4-coumarate 3-hydroxylase,
      hydroxycinnamoyl CoA quinate/shikimate hydroxycinnamoyl transferase, ferulate 5
      hydroxylase or caffeic acid 3-O-methyltransferase resulted in compositional
      changes in lignin and wall-bound hydroxycinnamic acids consistent with the
      current models of the monolignol pathway. However, downregulating caffeoyl CoA 3
      O-methyltransferase neither reduced syringyl (S) lignin units nor wall-bound
      ferulate, inconsistent with a role for this enzyme in 3-O-methylation ofS
      monolignol precursors and hydroxycinnamic acids. Paradoxically, lignin
      composition differed in plants downregulated in either cinnamate 4-hydroxylase or
      phenylalanine ammonia-lyase. No changes in the levels of acylated flavonoids were
      observed in the various transgenic lines. The current model for monolignol and
      ferulate biosynthesis appears to be an over-simplification, at least in alfalfa,
      and additional enzymes may be needed for the 3-O-methylation reactions of S
      lignin and ferulate biosynthesis.

PMID- 16972869
TI  - Cross-talk between ethylene and drought signalling pathways is mediated by the
      sunflower Hahb-4 transcription factor.
AB  - Hahb-4 is a member of the Helianthusannuus (sunflower) subfamily I of HD-Zip
      proteins that is transcriptionally regulated by water availability and abscisic
      acid. Transgenic Arabidopsis thaliana plants overexpressing this transcription
      factor (TF) exhibit a characteristic phenotype that includes a strong tolerance
      to water stress. Here we show that this TF is a new component of ethylene
      signalling pathways, and that it induces a marked delay in senescence. Plants
      overexpressing Hahb-4 are less sensitive to external ethylene, enter the
      senescence pathway later and do not show the typical triple response.
      Furthermore, transgenic plants expressing this gene under the control of its own
      inducible promoter showed an inverse correlation between ethylene sensitivity and
      Hahb-4 levels. Potential targets of Hahb-4 were identified by comparing the
      transcriptome of Hahb-4-transformed and wild-type plants using microarrays and
      quantitative RT-PCR. Expression of this TF has a major repressive effect on genes
      related to ethylene synthesis, such as ACO and SAM, and on genes related to
      ethylene signalling, such as ERF2 and ERF5. Expression studies in sunflower
      indicate that Hahb-4 transcript levels are elevated in mature/senescent leaves.
      Expression of Hahb-4 is induced by ethylene, concomitantly with several genes
      homologous to the targets identified in the transcriptome analysis (HA-ACOa and
      HA-ACOb). Transient transformation of sunflower leaves demonstrated the action of
      Hahb-4 in the regulation of ethylene-related genes. We propose that Hahb-4 is
      involved in a novel conserved mechanism related to ethylene-mediated senescence
      that functions to improve desiccation tolerance.

PMID- 16972870
TI  - DamID, a new tool for studying plant chromatin profiling in vivo, and its use to
      identify putative LHP1 target loci.
AB  - We show here that the in vivo methylation-based tagging technique DamID (DNA
      adenine methyltransferase identification) can be used for studies of DNA-protein
      interactions or chromatin profiling in plants. We have demonstrated the
      feasibility, reproducibility and sensitivity of the method in Arabidopsis
      thaliana, using the well-known yeast GAL4 transcription factor, for which DNA
      binding sites (UAS(G)) were introduced into the plant genome. We monitored the
      methylation resulting from the activity of DNA adenine methyltransferase fused to
      the protein of interest, by combining digestion with methylation-sensitive
      restriction enzymes and quantitative PCR. We then used DamID to identify genomic
      targets of LHP1, a protein mostly associated with euchromatin. We showed that
      LHP1 was targeted to the promoter and transcribed regions of four genes: AG, AP3,
      FT and PI. Our data also demonstrate that LHP1, like its animal homologues, has a
      high binding affinity for A/T-rich regions, binding particularly strongly to the
      large regulatory introns of AG and PI. We identified three major characteristics
      of LHP1 binding, highlighting the similarities between plant LHP1 and animal HP1
      proteins.

PMID- 16972872
TI  - The ecology of virulence.
AB  - Theoretical work has shown that parasites should evolve intermediate levels of
      virulence. Less attention has been given to the ecology of virulence. Here I
      explore population-dynamic models of infection in an annual host. The infection
      does not kill the host; but it can decrease the number of offspring produced by
      the host, and the magnitude of this effect depends on host population size.
      Hence, 'virulence' is density dependent, and is defined here as the difference in
      birth rates between uninfected and infected hosts, divided by the birth rate of
      uninfected hosts. The results suggest that infection can be highly virulent at
      the host's equilibrium density, even though the parasite has no effect on the
      host's intrinsic birth rate. The results also suggest that parasites may help to
      stabilize host population dynamics. In general, the impact of infection may be
      underestimated in natural populations.

PMID- 16972873
TI  - Reconciling differences in trophic control in mid-latitude marine ecosystems.
AB  - The dependence of long-term fishery yields on primary productivity, largely based
      on cross-system comparisons and without reference to the potential dynamic
      character of this relationship, has long been considered strong evidence for
      bottom-up control in marine systems. We examined time series of intensive
      empirical observations from nine heavily exploited regions in the western North
      Atlantic and find evidence of spatial variance of trophic control. Top-down
      control dominated in northern areas, the dynamics evolved from bottom-up to top
      down in an intermediate region, and bottom-up control governed the southern
      areas. A simplified, trophic control diagram was developed accounting for top
      down and bottom-up forcing within a larger region whose base state dynamics are
      bottom-up and can accommodate time-varying dynamics. Species diversity and ocean
      temperature co-varied, being relatively high in southern areas and lower in the
      north, mirroring the shifting pattern of trophic control. A combination of
      compensatory population dynamics and accelerated demographic rates in southern
      areas seems to account for the greater stability of the predator species complex
      in this region.

PMID- 16972874
TI  - Multiple risk reduction mechanisms: can dormancy substitute for dispersal?
AB  - In a spatiotemporally variable environment, plants use seed dispersal and
      dormancy to reduce risk. Intuition suggests that dormancy should be able to
      substitute for dispersal, so that dormancy will reduce the optimal mean dispersal
      distance, and previous theoretical studies using temporally uncorrelated
      environments have found this to be true. I show that in the presence of positive
      temporal correlations, dormancy instead increases dispersal: dormancy and
      dispersal are not interchangeable risk reduction mechanisms. Dispersal has both
      costs (seeds landing in unfavourable habitat) and benefits (seeds being in place
      to exploit newly favourable habitat). I discuss how the costs and benefits
      balance to determine optimal dispersal and how dormancy shifts this balance,
      causing dispersal to increase. I also find that an interaction between spatial
      and temporal correlations determines whether an evolutionarily stable dispersal
      distance exists at all and confirm the expectation that increasing the scale of
      spatial correlations causes dispersal to increase.

PMID- 16972875
TI  - Global estimates of shark catches using trade records from commercial markets.
AB  - Despite growing concerns about overexploitation of sharks, lack of accurate,
      species-specific harvest data often hampers quantitative stock assessment. In
      such cases, trade studies can provide insights into exploitation unavailable from
      traditional monitoring. We applied Bayesian statistical methods to trade data in
      combination with genetic identification to estimate by species, the annual number
      of globally traded shark fins, the most commercially valuable product from a
      group of species often unrecorded in harvest statistics. Our results provide the
      first fishery-independent estimate of the scale of shark catches worldwide and
      indicate that shark biomass in the fin trade is three to four times higher than
      shark catch figures reported in the only global data base. Comparison of our
      estimates to approximated stock assessment reference points for one of the most
      commonly traded species, blue shark, suggests that current trade volumes in
      numbers of sharks are close to or possibly exceeding the maximum sustainable
      yield levels.

PMID- 16972876
TI  - Resource availability controls fungal diversity across a plant diversity
      gradient.
AB  - Despite decades of research, the ecological determinants of microbial diversity
      remain poorly understood. Here, we test two alternative hypotheses concerning the
      factors regulating fungal diversity in soil. The first states that higher levels
      of plant detritus production increase the supply of limiting resources (i.e.
      organic substrates) thereby increasing fungal diversity. Alternatively, greater
      plant diversity increases the range of organic substrates entering soil, thereby
      increasing the number of niches to be filled by a greater array of heterotrophic
      fungi. These two hypotheses were simultaneously examined in experimental plant
      communities consisting of one to 16 species that have been maintained for a
      decade. We used ribosomal intergenic spacer analysis (RISA), in combination with
      cloning and sequencing, to quantify fungal community composition and diversity
      within the experimental plant communities. We used soil microbial biomass as a
      temporally integrated measure of resource supply. Plant diversity was unrelated
      to fungal diversity, but fungal diversity was a unimodal function of resource
      supply. Canonical correspondence analysis (CCA) indicated that plant diversity
      showed a relationship to fungal community composition, although the occurrence of
      RISA bands and operational taxonomic units (OTUs) did not differ among the
      treatments. The relationship between fungal diversity and resource availability
      parallels similar relationships reported for grasslands, tropical forests, coral
      reefs, and other biotic communities, strongly suggesting that the same underlying
      mechanisms determine the diversity of organisms at multiple scales.

PMID- 16972877
TI  - Tradeoffs of different types of species occurrence data for use in systematic
      conservation planning.
AB  - Data on the occurrence of species are widely used to inform the design of reserve
      networks. These data contain commission errors (when a species is mistakenly
      thought to be present) and omission errors (when a species is mistakenly thought
      to be absent), and the rates of the two types of error are inversely related.
      Point locality data can minimize commission errors, but those obtained from
      museum collections are generally sparse, suffer from substantial spatial bias and
      contain large omission errors. Geographic ranges generate large commission errors
      because they assume homogenous species distributions. Predicted distribution data
      make explicit inferences on species occurrence and their commission and omission
      errors depend on model structure, on the omission of variables that determine
      species distribution and on data resolution. Omission errors lead to identifying
      networks of areas for conservation action that are smaller than required and
      centred on known species occurrences, thus affecting the comprehensiveness,
      representativeness and efficiency of selected areas. Commission errors lead to
      selecting areas not relevant to conservation, thus affecting the
      representativeness and adequacy of reserve networks. Conservation plans should
      include an estimation of commission and omission errors in underlying species
      data and explicitly use this information to influence conservation planning
      outcomes.

PMID- 16972878
TI  - Quantifying the evidence for biodiversity effects on ecosystem functioning and
      services.
AB  - Concern is growing about the consequences of biodiversity loss for ecosystem
      functioning, for the provision of ecosystem services, and for human well being.
      Experimental evidence for a relationship between biodiversity and ecosystem
      process rates is compelling, but the issue remains contentious. Here, we present
      the first rigorous quantitative assessment of this relationship through meta
      analysis of experimental work spanning 50 years to June 2004. We analysed 446
      measures of biodiversity effects (252 in grasslands), 319 of which involved
      primary producer manipulations or measurements. Our analyses show that:
      biodiversity effects are weaker if biodiversity manipulations are less well
      controlled; effects of biodiversity change on processes are weaker at the
      ecosystem compared with the community level and are negative at the population
      level; productivity-related effects decline with increasing number of trophic
      links between those elements manipulated and those measured; biodiversity effects
      on stability measures ('insurance' effects) are not stronger than biodiversity
      effects on performance measures. For those ecosystem services which could be
      assessed here, there is clear evidence that biodiversity has positive effects on
      most. Whilst such patterns should be further confirmed, a precautionary approach
      to biodiversity management would seem prudent in the meantime.

PMID- 16972879
TI  - Assessing the ecology in ecotoxicology: a review and synthesis in freshwater
      systems.
AB  - The field of ecotoxicology is experiencing a surge in attention among ecologists
      as we gain a deeper appreciation for how contaminants can impact natural
      ecosystems. This interest is particularly strong in aquatic systems where many
      non-target organisms experience pesticides. In this article, we assess how
      pesticides affect freshwater systems by applying the conceptual framework of
      density- and trait-mediated indirect effects from the field of basic ecology. We
      demonstrate the utility of this framework for understanding the conditions under
      which pesticides affect species interactions, communities and ecosystems. Through
      the integration of laboratory toxicity tests and this ecological framework,
      ecotoxicologists should be better able to identify the mechanisms through which
      pesticides affect communities and ecosystems. We also identify several areas of
      research that are in critical need of empirical attention including synergistic
      effects between pesticides and natural stressors, the importance of pesticides on
      community assembly via habitat preferences and oviposition effects, the timing
      and frequency of pesticide applications, pesticide effects on population
      dynamics, the evolution of pesticide resistance in non-target organisms and
      ecosystem recovery. With this knowledge, one can improve upon management
      decisions and help protect non-target species that are of conservation concern.

PMID- 16972880
TI  - Expression of CD34 as a novel marker for glioneuronal lesions associated with
      chronic intractable epilepsy.
AB  - The spectrum of glioneuronal lesions underlying intractable epilepsies includes
      malformative pathologies like focal cortical dysplasia (FCD); and neoplastic
      lesions like gangliogliomas (GG) and dysembryoplastic neuroepithelial tumours
      (DNT). These may occur either singly or as dual lesions, having simultaneous
      presence of both elements. Currently, the relationship between the malformative
      and neoplastic glioneuronal lesions is poorly understood. Recently, CD34, a stem
      cell marker transiently expressed during early neurulation, has been identified
      in these tumours. This study was undertaken to (i) evaluate the role of CD34 as a
      diagnostic marker for glioneuronal lesions of epilepsy, namely, GG, DNT and FCD,
      and (ii) attempt to define the relationship among these lesions, using CD34 as a
      marker. Tissues resected from 47 patients with intractable epilepsy due to
      glioneuronal lesions (GG, FCD, DNT) were studied. These were evaluated for CD34
      expression, using immunohistochemistry. Dysplastic or atypically differentiated
      neural precursors which could not be identified on routine haematoxylin and eosin
      (H&E) staining were highlighted by CD34 immunostaining. The pattern of
      immunostaining was diffuse in GGs, unlike FCDs, wherein cells were present singly
      or in small clusters. However, cases of DNT and control tissue were largely CD34
      immunonegative. Based on these findings, we propose a possible common origin of
      GG and FCD, from a bipotent precursor that undergoes abnormal glioneuronal
      development, while DNTs possibly have a different origin. The CD34-immunoreactive
      cells represent dysplastic or undifferentiated neural precursors, which may
      signify a valuable marker for the diagnostic evaluation of neoplastic and/or
      malformative pathologies in patients with intractable epilepsy.

PMID- 16972881
TI  - Distinct patterns of serum immunoreactivity as evidence for multiple brain
      directed autoantibodies in juvenile neuronal ceroid lipofuscinosis.
AB  - Autoantibodies to glutamic acid decarboxylase (GAD65) have been reported in sera
      from the Cln3(-/-) mouse model of juvenile neuronal ceroid lipofuscinosis (JNCL),
      and in individuals with this fatal paediatric neurodegenerative disorder. To
      investigate the existence of other circulating autoreactive antibodies, we used
      sera from patients with JNCL and other forms of neuronal ceroid lipofuscinosis
      (NCL) as primary antisera to stain rat and human central nervous system sections.
      JNCL sera displayed characteristic patterns of IgG, but not IgA, IgE or IgM
      immunoreactivity that was distinct from the other forms of NCL. Immunoreactivity
      of JNCL sera was not confined to GAD65-positive (GABAergic) neurons, but also
      stained multiple other cell populations. Preadsorption of JNCL sera with
      recombinant GAD65 reduced the intensity of the immunoreactivity, but did not
      significantly change its staining pattern. Moreover, sera from Stiff Person
      Syndrome and Type I Diabetes, disorders in which GAD65 autoantibodies are
      present, stained with profiles that were markedly different from JNCL sera.
      Collectively, these studies provide evidence of the presence of autoreactive
      antibodies within multiple forms of NCL, and are not exclusively directed towards
      GAD65.

PMID- 16972882
TI  - Reduced minicolumns in the frontal cortex of patients with autism.
AB  - Cell minicolumns were shown to be narrower in frontal regions in brains of
      autistic patients compared with controls. This was not found in primary visual
      cortex. Within the frontal cortex, dorsal and orbital regions displayed the
      greatest differences while the mesial region showed the least change. We also
      found that minicolumns in the brain of a 3-year-old autistic child were
      indistinguishable from those of the autistic adult in two of three frontal
      regions, in contrast to the control brains. This may have been due to the small
      size of the columns in the adult autistic brain rather than to an accelerated
      development. The presence of narrower minicolumns supports the theory that there
      is an abnormal increase in the number of ontogenetic column units produced in
      some regions of the autistic brain during corticoneurogenesis.

PMID- 16972883
TI  - Molecular chaperons, amyloid and preamyloid lesions in the BRI2 gene-related
      dementias: a morphological study.
AB  - Molecular chaperons or amyloid-associated proteins (AAPs) are deposited in
      vascular and parenchymal amyloid lesions in Alzheimer's disease (AD) and other
      amyloidoses. AAPs, such as apolipoprotein E (ApoE) or apolipoprotein J (ApoJ)
      have been strongly implicated in the pathogenesis of AD in vitro and in vivo.
      Furthermore the possession of the ApoE in4 allele is a well-studied risk factor
      for AD. In view of the similarities between AD and both familial British dementia
      (FBD) and familial Danish dementia (FDD), we investigated the presence of AAPs in
      these two diseases to understand better their role in the general process of
      amyloidogenesis. Immunohistochemistry for ApoE, ApoJ, serum amyloid P (SAP),
      alpha-1-antichymotrypsin, cystatin C, heparan sulphate proteoglycans, such as
      agrin, perlecan, syndecans, glypican-1 and for heparan sulphate glycosaminoglycan
      (HS GAG) side chains was carried out together with immunohistochemical
      preparations specific to the amyloid subunits. Significant or extensive staining
      for ApoE, ApoJ, agrin, glypican-1 and HS GAG side chains was found in both
      amyloid (fibrillar) and preamyloid (nonfibrillar) deposits in FBD and FDD. The
      remaining AAPs, including SAP, were predominantly found in amyloid lesions. Only
      very weak staining was present in a small proportion of the amyloid lesions using
      perlecan immunohistochemistry. These findings suggest that the deposition
      patterns of AAPs in FBD and FDD are mostly similar to those in AD. The presence
      of AAPs in the preamyloid lesions supports the notion that chaperon molecules may
      play a role in the early steps of fibrillogenesis.

PMID- 16972884
TI  - Lysosome-associated membrane protein 1 (LAMP-1) in Alzheimer's disease.
AB  - Lysosome-associated membrane protein 1 (LAMP-1) is a glycoprotein highly
      expressed in lysosomal membranes. The present study was initiated to test LAMP-1
      mRNA and protein levels in post mortem frontal cortex (area 8) of Alzheimer's
      disease (AD) stages I-IIA/B and stages V-VIC of Braak and Braak, compared with
      age-matched controls. TaqMan PCR assays and Western blots demonstrated
      upregulation of LAMP-1 mRNA and protein in the cerebral cortex in ADVC. In
      addition, immunohistochemical studies have shown increased LAMP-1
      immunoreactivity in neurones, and in glial cells surrounding senile plaques, in
      AD cases. Interestingly, LAMP-1 immunoreactivity has little correlation with
      phosphorylated tau deposition and neurofibrillary tangles (NFTs), as neurones
      with NFTs were rarely LAMP-1 immunoreactive. In contrast, LAMP-1 expression was
      enhanced in neurones with granulovacuolar degeneration. Finally, LAMP-1 occurred
      in microglia and multinucleated giant cells in one AD case in whom amyloid burden
      was cleared following betaA-peptide immunization. These findings support the
      participation of lysosomes in betaA-amyloid and, probably, in hyperphosphorylated
      tau turnover in AD.

PMID- 16972885
TI  - DNA methylation and allelic losses on chromosome arm 14q in oligodendroglial
      tumours.
AB  - Cytogenetic and molecular genetic studies have shown frequent losses on the long
      arm of chromosome 14 in different types of human gliomas. Using differential
      methylation hybridization as a genome-wide screening approach to determine DNA
      methylation patterns in gliomas, we recently identified two DNA fragments in
      14q23.1 (CGI-clone musical sharp396) and 14q32.12 (CGI-clone musical sharp519)
      that were differentially methylated between astrocytic gliomas and mixed
      oligoastrocytomas. To validate this observation, we examined these 14q32.12 locus
      for methylation in an extended series of 43 astrocytic and oligodendroglial
      gliomas. All tumours were additionally investigated for loss of heterozygosity
      (LOH). Microsatellite analysis showed LOH in seven of 28 (25%) oligodendroglial
      tumours and three of 15 (20%) astrocytic tumours. Seven tumours demonstrated LOH
      at all informative 14q loci whereas three tumours carried partial deletions
      defining a commonly deleted region at 14q22.3-q32.1 between the microsatellite
      markers D14S282 and D14S995. Methylation-specific PCR analysis of the 14q32.12
      locus revealed hypermethylation in 12 of 43 gliomas (28%). Hypermethylation was
      restricted to tumours with oligodendroglial differentiation (12 of 28 tumours,
      43%). However, none of the hypermethylated tumours demonstrated LOH on 14q and
      vice versa. In total, 19 of 28 oligodendroglial tumours (68%) showed either
      hypermethylation at the 14q32.12 locus or LOH at 14q22.3-q32.2. Taken together,
      our data lend further support for the location of one or more yet to be
      identified glioma-associated tumour suppressor gene(s) on 14q. In addition, the
      restriction of 14q32.12 methylation to oligodendroglial tumours suggests a role
      for epigenetic DNA modifications in these particular gliomas.

PMID- 16972886
TI  - Patterns of SPARC expression and basement membrane intactness at the tumour-brain
      border of invasive meningiomas.
AB  - The matricellular glycoprotein SPARC (secreted protein, acidic and rich in
      cysteine), also termed osteonectin, has been found to regulate the invasive
      behaviour of several tumour types by interacting with basement membrane
      constituents. Brain invasive meningiomas are supposed to disrupt the pial-glial
      basement membrane. In the present study we aimed at determining the relationship
      of basement membrane intactness and SPARC protein expression at the meningioma
      brain border. Sections of 51 brain-invasive meningiomas (31 meningothelial
      meningiomas WHO grade I, 11 atypical WHO grade II, and nine anaplastic WHO grade
      III tumours) were immunolabelled with antibodies against SPARC, epithelial
      membrane antigen (EMA), collagen IV and glial fibrillary acidic protein (GFAP).
      Twenty-two non-invasive WHO grade I meningothelial meningiomas were included in
      the study for comparison. At the tumour-brain border of invasive meningiomas,
      spindle-shaped tumour cells expressed SPARC. The number of tumours containing
      SPARC+ spindle cells did not differ significantly between WHO grades. By
      contrast, the number of WHO grade I tumours expressing collagen IV (15/31) was
      highly significantly elevated when compared with WHO grade II (1/11) and WHO
      grade III (0/9) (both P < 0.0001). There was an inverse relationship of the
      presence of SPARC+ spindle cells and basement membrane material. In conclusion,
      the destruction of the basement membrane is correlated with meningioma malignancy
      grade whereas the expression of SPARC protein at the tumour-brain border is not.
      Destruction of the basement membrane and appearance of SPARC+ spindle cells are
      not coincident during the course of brain invasion by meningiomas.

PMID- 16972887
TI  - Tumour vascularity is of prognostic significance in adult, but not paediatric
      astrocytomas.
AB  - Astrocytomas are the commonest type of brain tumours in adults and children.
      Although the most reliable prognostic indicators have been shown consistently to
      be patient age and tumour histological grade, biological progression in these
      tumours is inevitable and the overall prognosis has remained poor. Due to the
      evidence that vascular changes are important histological features of
      astrocytomas, the aim of this study was to investigate prognostic significance of
      tumour vascularity in paediatric and adult astrocytomas. Study population
      consisted of 70 patients (45 adult and 25 children) with histologically proven
      diagnosis of astrocytoma with no history of previous therapy. Histological
      quantification of tumour vascularity was performed using three different methods:
      microvessel density, vascular grading and Chalkley counting. Histological
      classification and grading were also assessed using the World Health Organization
      system. In contrast to the results in paediatric astrocytomas, tumour vascularity
      in adult tumours correlated significantly with postoperative survival by
      univariate analysis (P < 0.05). Microvessel density appeared to be an independent
      indicator of prognosis by multivariate analysis (P = 0.001). Likewise, patients
      with microvessel density of 70 or greater had significantly shorter survival than
      the remaining group (P < 0.001). Patient age and tumour histological grade were
      also correlated with survival. We conclude that histological quantification of
      tumour vascularity is a significant prognosticator in adult astrocytomas, but not
      in children. Our data do not support the validity of applications of
      antiangiogenic agents in paediatric astrocytic tumours, particularly pilocytic
      astrocytomas.

PMID- 16972888
TI  - Regression stage senile plaques in the natural course of Alzheimer's disease.
AB  - Resolution process of cerebroparenchymal amyloid beta-protein (Abeta) deposition
      has become of increasing interest in the light of recent advance in the Abeta
      vaccination therapy for Alzheimer's disease (AD). However, the neuropathological
      features of degraded and disappearing senile plaque remain poorly characterized,
      especially in the natural course of the disease. To clarify the natural removal
      processes of Abeta burden in the brain with AD, we devised a triple-step staining
      method: Bodian for dystrophic neurites, anti-glial fibrillary acidic protein for
      astrocytes, and anti-Abeta. We thus examined 24 autopsied AD brains. A novel form
      of senile plaques, termed 'remnant plaques', was identified. Remnant plaques were
      characterized by mesh-like astroglial fibrils within the entire plaque part,
      Abeta deposit debris exhibiting weak Abeta immunoreactivity, and only a few
      slender dystrophic neurites. In remnant plaques, amyloid burden was apparently
      decreased. The density of remnant plaques increased significantly with disease
      duration. Dual-labelling immunohistochemistry revealed many Abeta-immunoreactive
      granules in astrocytes and a modest number in microglia, both of which
      accumulated in senile plaques. We consider amyloid deposits of diffuse and
      neuritic plaques to be shredded by astrocytic processes from the marginal zone of
      plaques, and to gradually disintegrate into smaller compartments.
      Cerebroparenchymal Abeta deposits undergo degradation. After a long-standing
      resolution process, diffuse and neuritic plaques may finally proceed to remnant
      plaques. Astrocytes are actively engaged in the natural Abeta clearance mechanism
      in advanced stage AD brains, which may provide clues for developing new
      therapeutic strategies for AD.

PMID- 16972889
TI  - Primary intracranial angiosarcoma of the Pineal gland: an unusual cause of
      recurrent intraventricular haemorrhage and superficial haemosiderosis.

PMID- 16972890
TI  - Histone deacetylase (HDAC) 4 involvement in both Lewy and Marinesco bodies.

PMID- 16972893
TI  - A historical perspective on immunological privilege.
AB  - Intimations of immunological privilege in sites of the body such as the eye and
      the brain go back in the literature more than a century, to reports of
      experiments using outbred animals and tumor transplants. The starting points of
      this review, however, are publications stemming from the transplantation of
      normal tissues and, as far as possible, the use of inbred animals, exploring the
      way in which interplay between genetic differences of different degree, from
      single minor histocompatibility antigens to full-house major histocompatibility
      complex mismatches, has been reported to affect the 'take' of grafts in
      putatively privileged sites. While these sites traditionally included the brain,
      the eye, the pregnancy, and the endocrine tissues such as thyroid, parathyroid,
      adrenal, and islets of Langerhans, from readings of the literature, it is clear
      that the eye and the pregnancy have claims to being in the strongest positions of
      privilege. Even then, the position is precarious, with stirrings of the adaptive
      immune system poised to attack. Various regulatory mechanisms have now moved
      center stage and will undoubtedly form a significant part in subsequent chapters
      in this volume. Perhaps surprisingly, as investigations on these mechanisms have
      advanced, there is evidence for the convergence of those mechanisms controlling
      both induced tolerance and immunological privilege.

PMID- 16972894
TI  - Ocular autoimmunity: the price of privilege?
AB  - The eye is the prototypic immune-privileged organ. Its antigens were once
      believed to be expressed exclusively in the eye, which resides behind an
      efficient blood-organ barrier, and were believed to be unknown to the immune
      system. Self-tolerance to ocular components was therefore believed to be based
      not on immune tolerance but on immune ignorance. It is now known that the
      relationship between the immune system and the eye is much more complex. On the
      one hand, immune privilege is now known to involve not only sequestration but
      also active mechanisms that (i) inhibit innate and adaptive immune processes
      within the eye and (ii) shape the response that develops systemically to antigens
      released from the eye. On the other hand, retinal antigens are found in the
      thymus and have been shown to shape the eye-specific T-cell repertoire. However,
      thymic elimination of self-reactive T cells is incomplete, and such 'escapee' T
      cells are tolerized in the periphery as they recirculate through the body by
      encounter with self-antigen in healthy tissues. Due to the relative
      inaccessibility of the healthy eye to the immune system, peripheral tolerance
      mechanisms may not operate efficiently for ocular antigens, leaving a weak link
      in the homeostasis of tolerance. The case shall be made that although immune
      privilege protects vision by keeping the immune system at bay, a potential for
      developing destructive anti-retinal autoimmunity may be the price for the day-to
      day protection afforded by immune privilege against inflammatory insults.

PMID- 16972895
TI  - Stranger in a strange land.
AB  - Mammalian mothers and their embryos/fetuses are almost invariably genetically
      different, which raises the question of how the mother's immune system is
      diverted so as to permit cohabitation with the 'foreign' body. Several decades of
      research have shown that multiple cooperative systems sanction uteroplacental
      immune privilege. These systems include production of several varieties of
      soluble immunosuppressive molecules in the uterus and the placenta and strict
      regulation of the molecules expressed on or by placental trophoblast cells.
      Trophoblast, a unique lineage without counterpart in adult tissues, is in direct
      contact with maternal blood and tissue. The major graft rejection-promoting
      molecules, human leukocyte antigens (HLAs), are tightly regulated in these cells,
      with none of HLA-A, HLA-B, or HLA class II antigens expressed. The HLA class Ib
      antigens, HLA-E, HLA-F, and HLA-G, are detectable on some subpopulations. Our
      studies have focused on the expression, regulation, and functions of the soluble
      isoforms of HLA-G, which circulate in maternal blood and are present at high
      levels in the pregnant uterus. These isoforms are derived from the single HLA-G
      gene by alternative splicing and are now known to have immunosuppressive
      properties. Ours and other studies indicate that soluble HLA-G proteins may
      comprise a unique tolerogenic system for establishing local immune privilege
      during pregnancy.

PMID- 16972897
TI  - The testis in immune privilege.
AB  - The production, differentiation, and presence of male gametes represent
      inimitable challenges to the immune system, as they are unique to the body and
      appear long after the maturation of the immune system and formation of systemic
      self-tolerance. Known to protect germ cells and foreign tissue grafts from
      autoimmune attack, the 'immune privilege' of the testis was originally, and
      somewhat simplistically, attributed to the existence of the blood-testis barrier.
      Recent research has shown a previously unknown level of complexity with a
      multitude of factors, both physical and immunological, necessary for the
      establishment and maintenance of the immunotolerance in the testis. Besides the
      blood-testis barrier and a diminished capability of the large testicular resident
      macrophage population to mount an inflammatory response, it is the constitutive
      expression of anti-inflammatory cytokines in the testis by immune and
      particularly somatic cells, that represents an essential element for local
      immunosuppression. The role of androgens in testicular immune regulation has long
      been underestimated; yet, accumulating evidence now shows that they orchestrate
      the inhibition of proinflammatory cytokine expression and shift cytokine balance
      toward a tolerogenic environment. Furthermore, the role of the testicular
      dendritic cells in suppressing antigen-specific immunity and T-lymphocyte
      activation is discussed. Finally, the active role mast cells play in the
      induction and amplification of immune responses, both in infertile humans and in
      experimental models, highlights the importance of preventing mast cell activation
      to maintain the immune-privileged status of the testis.

PMID- 16972896
TI  - CNS immune privilege: hiding in plain sight.
AB  - Central nervous system (CNS) immune privilege is an experimentally defined
      phenomenon. Tissues that are rapidly rejected by the immune system when grafted
      in sites, such as the skin, show prolonged survival when grafted into the CNS.
      Initially, CNS immune privilege was construed as CNS isolation from the immune
      system by the blood-brain barrier (BBB), the lack of draining lymphatics, and the
      apparent immunoincompetence of microglia, the resident CNS macrophage. CNS
      autoimmunity and neurodegeneration were presumed automatic consequences of immune
      cell encounter with CNS antigens. Recent data have dramatically altered this
      viewpoint by revealing that the CNS is neither isolated nor passive in its
      interactions with the immune system. Peripheral immune cells can cross the intact
      BBB, CNS neurons and glia actively regulate macrophage and lymphocyte responses,
      and microglia are immunocompetent but differ from other macrophage/dendritic
      cells in their ability to direct neuroprotective lymphocyte responses. This newer
      view of CNS immune privilege is opening the door for therapies designed to
      harness autoreactive lymphocyte responses and also implies (i) that CNS
      autoimmune diseases (i.e. multiple sclerosis) may result as much from neuronal
      and/or glial dysfunction as from immune system dysfunctions and (ii) that the
      severe neuronal and glial dysfunction associated with neurodegenerative disorders
      (i.e. Alzheimer's disease) likely alters CNS-specific regulation of lymphocyte
      responses affecting the utility of immune-based therapies (i.e. vaccines).

PMID- 16972898
TI  - Immune privilege in the gut: the establishment and maintenance of non
      responsiveness to dietary antigens and commensal flora.
AB  - Immune privilege in the gut is the result of a complex interplay between the gut
      microbiome, gut luminal antigens, and the intestinal epithelial barrier. Composed
      of both physical and immunochemical components, the intestinal barrier secretes
      immunoregulatory mediators that promote the generation of tolerogenic antigen
      presenting cells, phagocytic innate immune cells characterized by 'inflammatory
      anergy', and regulatory cells of the adaptive immune system. Innate immune cells
      mediate controlled transepithelial transport of luminal antigens as far as the
      mesenteric lymph nodes, where the intestinal and peripheral immune systems
      intersect. This promotes the generation of adaptive regulatory lymphocytes that
      actively suppress effector cell responses against gut luminal antigens and flora.
      The net result is the generation of tolerance to dietary antigens and the
      maintenance of gut homeostasis. Dysregulation of this complex immunoregulatory
      network leads to diseases such as food allergy and inflammatory bowel disease.
      Future therapies for these diseases will likely involve the functional
      restoration of the barrier and regulatory cell functions at the
      epithelial/luminal interface.

PMID- 16972899
TI  - Cellular and molecular mechanisms of liver tolerance.
AB  - The liver exhibits a distinctive form of immune privilege, termed liver
      tolerance, in which orthotopic liver transplantation results in systemic donor
      specific T-cell tolerance, while antigens introduced either into hepatocytes or
      via the portal vein also cause tolerance. Here we argue that the fundamental
      mechanism driving liver tolerance is likely to be the continuous exposure of
      diverse liver cell types to endotoxin, derived from the intestinal bacteria. This
      exposure promotes the expression of a set of cytokines, antigen-presenting
      molecules, and costimulatory signals that impose T-cell inactivation, partly via
      effects on liver antigen-presenting cells. The evidence favors clonal deletion
      mechanisms and is consistent with a role for regulatory T cells but does not
      support either anergy or immune deviation as important factors in liver
      tolerance.

PMID- 16972900
TI  - The importance of regional lymph nodes for mucosal tolerance.
AB  - The immune system is organized as a number of distinct lymphoid organs
      interconnected by recirculating lymphocytes. These organs, such as lymph nodes,
      spleen, and gut-associated Peyer's patches, are compartmentalized, providing
      separate niches for T and B cells. In addition, regional compartmentalization of
      lymphoid organs themselves exists, leading to the distinction between the mucosal
      and the systemic immune systems. This distinction not only reflects the
      anatomical localization but also is based on functional differences, with
      predominant tolerance induction via mucosal routes and immunity seen after
      systemic antigen exposure. These differences are associated with regional
      differences in the lymphoid organs and with environmental conditions of the
      tissues in which the immune system functions. Recirculation patterns of
      lymphocytes differ between mucosal and systemic lymphoid organs, and more insight
      into the mechanisms that imprint this behavior has been generated recently.
      Differences in dendritic cells have been observed between mucosal and systemic
      sites, and knowledge on how local factors contribute to the immune system is
      emerging. From our studies on mucosal tolerance in mouse models, it has become
      evident that regional lymph nodes draining the mucosa are important sites to
      direct immune responses. Here, we discuss the way regional lymph nodes contribute
      to the direction of immune responses and what is known about the local factors
      and cell behavior that form the basis for these differences.

PMID- 16972901
TI  - Immune resistance orchestrated by the tumor microenvironment.
AB  - It is now little disputed that most if not all cancer cells express antigens that
      can be recognized by specific CD8(+) T lymphocytes. However, a central question
      in the field of anti-tumor immunity is why such antigen-expressing tumors are not
      spontaneously eliminated by the immune system. While in some cases, this lack of
      rejection may be due to immunologic ignorance, induction of anti-tumor T-cell
      responses in many patients has been detected in the peripheral blood, either
      spontaneously or in response to vaccination, without accompanying tumor
      rejection. These observations argue for the importance of barriers downstream
      from initial T-cell priming that need to be addressed to translate immune
      responses into clinical tumor regression. Recent data suggest that the proper
      trafficking of effector T cells into the tumor microenvironment may not always
      occur. T cells that do effectively home to tumor metastases are often found to be
      dysfunctional, pointing toward immunosuppressive mechanisms in the tumor
      microenvironment. T-cell anergy due to insufficient B7 costimulation, extrinsic
      suppression by regulatory cell populations, inhibition by ligands such as
      programmed death ligand-1, metabolic dysregulation by enzymes such as indoleamine
      2,3-dioxygenase, and the action of soluble inhibitory factors such as
      transforming growth factor-beta have all been clearly implicated in generating
      this suppressive microenvironment. Identification of these downstream processes
      points to new therapeutic targets that should be manipulated to facilitate the
      effector phase of anti-tumor immune responses in concert with vaccination or T
      cell adoptive transfer.

PMID- 16972902
TI  - The tumor-draining lymph node as an immune-privileged site.
AB  - Lymph nodes that lie immediately downstream of tumors [tumor-draining lymph nodes
      (TDLNs)] undergo profound alterations due to the presence of the upstream tumor.
      The antigen-presenting cell population in TDLNs becomes modified such that tumor
      derived antigens are cross-presented by host cells in a tolerizing fashion. In
      addition, the number and suppressor activity of regulatory T cells (Tregs) are
      increased in the TDLN. Emerging evidence suggests that some of these Tregs may be
      generated de novo against specific tumor-derived antigens, and thus they arise as
      a direct consequence of antigen presentation in the TDLN. Others may represent
      Tregs against self-antigens, which undergo preferential activation in the
      tolerogenic milieu of the TDLN. The TDLN thus becomes an anatomic context in
      which presentation of new antigens not only fails to elicit a protective immune
      response but also actively creates systemic tolerance. In this regard, the TDLN
      displays features analogous to classical immune privilege. Accumulating evidence
      thus suggests that the TDLNs, although small in size, may exert a profound
      tolerizing influence on the rest of the immune system. These mechanisms will need
      to be interrupted in order for clinical anti-tumor immunotherapy to be
      successful.

PMID- 16972903
TI  - Immune privilege in sites of chronic infection: Leishmania and regulatory T
      cells.
AB  - Leishmania are digenetic protozoan parasites that are inoculated into the skin by
      vector sand flies, are taken up by macrophages, and produce a spectrum of chronic
      diseases in their natural reservoir and susceptible human hosts. During the early
      establishment of infection in the skin and lymphoid organs, Leishmania produce
      multiple effects on macrophage and dendritic cell functions that inhibit their
      innate anti-microbial defenses and impair their capacity to initiate T-helper 1
      cell immunity. In addition, the skin is a site preconditioned for early parasite
      survival by virtue of a high frequency of steady-state, natural CD25+Foxp3+
      regulatory T cells (Tregs) that function to suppress the generation of unneeded
      immune responses to infectious and non-infectious antigens to which the skin is
      regularly exposed. In murine models of infection, antigen-induced CD25+/-Foxp3
      interleukin (IL)-10+ Treg cells act during the effector phase of the immune
      response to control immunopathology and may also delay or prevent healing.
      Finally, following resolution of infection in healed mice, CD25+Foxp3+ Tregs
      function in an IL-10-dependent manner to prevent sterile cure and establish a
      long-term state of functional immune privilege in the skin.

PMID- 16972904
TI  - Immune privilege and HIV-1 persistence in the CNS.
AB  - Human immunodeficiency virus-1 (HIV-1) neuroinvasion occurs early (during period
      of initial viremia), leading to infection of a limited amount of susceptible
      cells with low CD4 expression. Protective cellular and humoral immunity eliminate
      and suppress viral replication relatively quickly due to peripheral immune
      responses and the low level of initial central nervous system (CNS) infection.
      Upregulation of the brain protective mechanisms against lymphocyte entry and
      survival (related to immune privilege) helps reduce viral load in the brain. The
      local immune compartment dictates local viral evolution as well as selection of
      cytotoxic lymphocytes and immunoglobulin G specificity. Such status can be
      sustained until peripheral immune anti-viral responses fail. Activation of
      microglia and astrocytes, due to local or peripheral triggers, increases
      chemokine production, enhances traffic of infected cells into the CNS,
      upregulates viral replication in resident brain macrophages, and significantly
      augments the spread of viral species. The combination of these factors leads to
      the development of HIV-1 encephalitis-associated neurocognitive decline and
      patient death. Understanding the immune-privileged state created by virus, the
      brain microenvironment, and the ability to enhance anti-viral immunity offer new
      therapeutic strategies for treatment of HIV-1 CNS infection.

PMID- 16972905
TI  - Immune cell migration as a means to control immune privilege: lessons from the
      CNS and tumors.
AB  - Certain organs, such as the brain, eye, and gonads, are particularly sensitive to
      damage by inflammation. Therefore, these tissues have developed unique
      immunological properties that curtail inflammatory responses, a phenomenon termed
      immune privilege. In addition, by co-opting some of the regulatory cues operant
      in immune privilege in normal organs, tumors can evade immunosurveillance. While
      many different mechanisms contribute to immune privilege, there is evidence that
      leukocyte migration is an important checkpoint in its control. This hypothesis is
      based on the fact that leukocyte entry into these organs is restricted by
      physical barriers and that the collapse of these obstacles marks a critical step
      in the development of inflammatory/autoimmune disease at these sites. Numerous
      studies in a variety of experimental systems have characterized the molecular and
      cellular mechanisms involved in leukocyte homing to immune-privileged organs.
      Recently, two-photon microscopy has revealed critical insights into the events
      occurring in the extravascular space of immune-privileged organs, including
      locomotion patterns and interactive behavior of leukocytes in the interstitial
      space. Here, we review our current understanding of immune cell migration to and
      within immune-privileged organs and highlight how this knowledge may be exploited
      for immunotherapeutic purposes.

PMID- 16972906
TI  - TGF-beta: a mobile purveyor of immune privilege.
AB  - Functionally barricaded immune responses or sites of immune privilege are no
      longer considered dependent on specific anatomical considerations, but rather,
      they can develop in any location where immunoregulatory cells congregate and
      express or release products capable of deviating the host response to foreign
      antigens. Among the pivotal molecules involved in orchestrating these ectopic
      sites of immune suppression is transforming growth factor-beta (TGF-beta), a
      secreted and cell-associated polypeptide with a multiplicity of actions in innate
      and adaptive immunity. While beneficial in initiating and controlling immune
      responses and maintaining immune homeostasis, immunosuppressive pathways mediated
      by TGF-beta may obscure immune surveillance mechanisms, resulting in failure to
      recognize or respond adequately to self, foreign, or tumor-associated antigens.
      CD4+CD25+Foxp3+ regulatory T cells represent a dominant purveyor of TGF-beta
      mediated suppression and are found in infiltrating tumors and other sites of
      immune privilege, where they influence CD8+ T cells; CD4+ T-helper (Th)1, Th2,
      and Th17 cells; natural killer cells; and cells of myeloid lineage to choreograph
      and/or muck up host defense. Defining the cellular sources, mechanisms of action,
      and networking that distinguish the dynamic establishment of localized immune
      privilege is vital for developing strategic approaches to diminish or to
      embellish these tolerogenic events for therapeutic benefit.

PMID- 16972907
TI  - A vision of cell death: Fas ligand and immune privilege 10 years later.
AB  - Immune privilege is a term applied to organs that have a unique relationship with
      the immune response. These sites prohibit the spread of inflammation, since even
      minor episodes can threaten organ integrity and function. Once thought to be a
      passive process relying on physical barriers, immune privilege is now viewed as
      an active process, which uses multiple mechanisms to maintain organ function. The
      prototypic organ of immune privilege has been the eye, where the spread of
      inflammation can threaten vision. Nearly 10 years ago, we discussed the finding
      that Fas ligand (FasL) was constitutively expressed in the eye and played a major
      role in immune privilege by inducing apoptosis in inflammatory cells that enter
      the eye. In this review, we reexamine the original evidence for the role of FasL
      in immune privilege, update progress on some of the concepts, and discuss some of
      the issues that remain unresolved.

PMID- 16972908
TI  - Immune privilege induced by regulatory T cells in transplantation tolerance.
AB  - Immune privilege was originally believed to be associated with particular organs,
      such as the testes, brain, the anterior chamber of the eye, and the placenta,
      which need to be protected from any excessive inflammatory activity. It is now
      becoming clear, however, that immune privilege can be acquired locally in many
      different tissues in response to inflammation, but particularly due to the action
      of regulatory T cells (Tregs) induced by the deliberate therapeutic manipulation
      of the immune system toward tolerance. In this review, we consider the interplay
      between Tregs, dendritic cells, and the graft itself and the resulting local
      protective mechanisms that are coordinated to maintain the tolerant state. We
      discuss how both anti-inflammatory cytokines and negative costimulatory
      interactions can elicit a number of interrelated mechanisms to regulate both T
      cell and antigen-presenting cell activity, for example, by catabolism of the
      amino acids tryptophan and arginine and the induction of hemoxygenase and carbon
      monoxide. The induction of local immune privilege has implications for the design
      of therapeutic regimens and the monitoring of the tolerant status of patients
      being weaned off immunosuppression.

PMID- 16972913
TI  - Health-related quality of life among 3--4-year-old children born with very low
      birthweight.
AB  - AIM: This paper reports a study comparing health-related quality of life at 3-4
      years of age among children born with very low birthweight (<or=1500 g) to a
      group of non-very low birthweight controls, and to examine biological,
      environmental, demographic and health factors associated with quality of life of
      children born with very low birthweight. BACKGROUND: Advances in modern medicine
      have increased the survival of infants with very low birthweight, but its impact
      on quality of life of children during preschool years has been less studied.
      METHODS: The study sample included 118 children born with very low birthweight
      and 170 non-very low birthweight controls in Taiwan. Primary caregivers of the
      study children completed structured questionnaires during the period November
      2002 to April 2003. Health-related quality of life was measured using the
      Mandarin version of the TZO-AZL Preschool Children Quality of Life instrument.
      This tool has four dimensions: physical, emotional, cognitive and social
      functions. Higher scores indicate better quality of life. FINDINGS: Children born
      with very low birthweight had statistically significantly lower mean quality of
      life scores in all the four dimensions compared with controls. Among the former,
      those who had current physical health problems scored lower in all dimensions of
      quality of life. Primary caregivers with higher educational levels and increased
      ages of the children were associated with improved scores in the emotional and
      social functions. Birth gestational age was negatively associated with cognitive
      function. Length of stay in the neonatal intensive care unit was negatively
      associated with scores for the social function aspect of quality of life.
      CONCLUSION: Regular monitoring of the quality of life among very low birthweight
      children is needed. Nurses need to assess the child's current health state, birth
      gestational age, and the primary caregiver's educational level in order to
      identify those who are at risk for low quality of life and intervene early.

PMID- 16972914
TI  - The duality in using information and communication technology in elder care.
AB  - AIM: The aim of this paper is to report a study illuminating values and
      perceptions held by professional carers of older people about the use of
      information and communication technology applications. BACKGROUND: Various
      information and communication technology applications have successfully been
      developed to help solve a variety of problems in elder care. Beside different
      technical barriers and the assumed negative attitudes among older people, staff
      values and attitudes have been found to be an important cause of resistance to
      change and slowness in introduction of information and communication technology
      in health care of older people. METHODS: An interview study was conducted in 2004
      with 10 healthcare personnel with 3-26 years experience of working in home care
      and nursing homes in Northern Sweden. Qualitative content analysis was used to
      identify recurring themes in the data. RESULTS: The interpretation of values and
      perceptions among carers revealed a duality where the carers perceived
      information and communication technology as a promoter of both inhumane and
      humane care, a duality that seemed to make them defensive and resistant to
      change. Within the overall duality, other dualities were embedded that described
      both perceptions about the care of older people and about being a carer. There
      was evidence of resistance among professional carers towards an introduction of
      information and communication technology applications in elder care. Carers
      considered that the same attributes of information and communication technology
      that could promote humane care could also lead to dehumanized care. CONCLUSION:
      There should be an ethical discussion when introducing information and
      communication technology applications in elder care. The best caring alternative
      for all those concerned should be considered. It should promote aspects of
      wellbeing and dignity for frail older people and fears of inhumane care among
      carers must be recognized and discussed.

PMID- 16972915
TI  - Effects of an osteoporosis educational programme for men.
AB  - AIM: This paper reports an evaluation of the effects on knowledge, health beliefs
      and preventive behaviours of an osteoporosis educational programme for men.
      BACKGROUND: Osteoporosis is an increasing global health concern, and educational
      programmes have been identified as a crucial strategy in its prevention. However,
      the effectiveness of osteoporosis educational programmes has mainly been
      evaluated in women. METHODS: A randomized controlled trial was carried out to
      identify the effects of an osteoporosis educational programme for men. The study
      was conducted between September 2004 to February 2005, and 128 Hong Kong Chinese
      men were randomly assigned to an intervention or control group, with 64 in each
      group. The intervention group attended an osteoporosis educational programme. All
      participants completed pre- and post-test self-administered questionnaires:
      Osteoporosis Knowledge Test, Osteoporosis Health Belief Scale and Osteoporosis
      Self-Efficacy Scale. RESULTS: The intervention group showed a statistically
      significant increase in both knowledge (P < 0.0005) and health beliefs (P =
      0.007) about osteoporosis and preventive behaviours in comparison with the
      control group. However, the difference in self-efficacy between the two groups
      was not statistically significant (P = 0.154). CONCLUSIONS: An osteoporosis
      educational programme can increase men's knowledge levels and change their health
      beliefs about osteoporosis and preventive behaviours. This approach should be
      more widely used in nursing practice to promoting the adoption of osteoporosis
      prevention behaviours in men.

PMID- 16972916
TI  - Caregiver bodywork: family members' experiences of caring for a person with motor
      neurone disease.
AB  - AIM: This paper reports a study of how family members caring for people living
      with motor neurone disease managed the deteriorating body, their own bodywork and
      the associated emotional labour. BACKGROUND: People living with the
      neurodegenerative condition of motor neurone disease face the prospect of dying
      in 3-5 years from progressive loss of voluntary muscle mass and function,
      culminating in respiratory failure. Theories concerning the body in illness have
      been used to illustrate patient perspectives; however, family caregivers'
      experiences of the body have been neglected. METHOD: An ethnographic case study
      was undertaken with 18 primary family caregivers and six peripheral caregivers.
      Primary caregivers participated over 10 months in three face-to-face, semi
      structured interviews which included mapping their support networks using
      ecomaps. Observational data were also recorded as field notes. Peripheral
      caregivers were interviewed once during the same time period. The data were
      generated between 2003 and 2004. FINDINGS: Informal caregiving requires
      engagement in various aspects of bodywork. Three body concepts were identified:
      the visible body--how the disease affected the patient and caregivers; the
      dependent body--the resulting care requirements; and the social body--how living
      with motor neurone disease affected their social support networks. The visible
      body is a continual reminder of the ravages of the disease, while the dependent
      body demands physical and emotional care. Social interactions decline over time,
      depriving family caregivers of the much needed support for sustaining their
      commitment to the bodywork required in caregiving. CONCLUSION: The demands of
      bodywork for family caregivers are increased by the continual presence of
      emotional labour as they seek to implement the best way to support their relative
      with motor neurone disease. Nurses and allied healthcare workers need to assess
      each family situation, asking appropriate questions to establish the most
      appropriate interventions to facilitate supportive care.

PMID- 16972917
TI  - Self-management profiles and metabolic outcomes in type 2 diabetes.
AB  - AIM: This paper reports a study whose aims were (1) to examine whether it is
      possible to determine participants' self-management profiles using three open
      ended questions about their self-perceived role in diabetes management; and (2)
      to analyse whether such self-management profiles have any bearing on haemoglobin
      A(1c) levels. BACKGROUND: The behavioural and educational aspects of self
      management in type 2 diabetes have been the topic of a number of investigations.
      The individual's role in maintaining health and a satisfying everyday life with
      chronic conditions is increasingly becoming the focus of secondary prevention.
      METHOD: Participants (n = 259) were recruited from those attending a year-long
      health educational programme for people with type 2 diabetes at Swedish
      pharmacies. A questionnaire was distributed 24 months after baseline. The health
      outcome, haemoglobin A(1c) was measured on four occasions. Three open-ended
      questions were used to explore self-management profiles based on perceived role,
      goal, and need of support in treatment. Data were collected during the period
      1997-2002. FINDINGS: The following profiles of participants emerged: Disease
      Manager, Compliant, and Disheartened, with no initial differences in metabolic
      control. However, during the programme Disease Managers achieved good glycaemic
      control and succeeded in maintaining the reduction in their blood glucose for a
      longer period than those in other categories: their haemoglobin A(1c) level was
      reduced by -0.35 at 6 months (P = 0.000), -0.30 at 12 months (P = 0.001), and 
      0.28 at 24 months (P = 0.001) after baseline. Compliant participants had a good
      everyday routine and a -0.18 reduction at 6 months (P = 0.028) but no
      statistically significant haemoglobin A(1c) level reduction later. A smaller
      group of people, the Disheartened, reported difficulties in living with diabetes
      and did not succeed in decreasing their haemoglobin A(1c) by statistically
      significant amounts. CONCLUSION: Healthcare professionals could use our three
      open-ended questions to assist in understanding people's views of their role in
      disease management so that health promotion and education can be tailored to
      individual needs.

PMID- 16972918
TI  - Triangulation of qualitative approaches: hermeneutical phenomenology and grounded
      theory.
AB  - AIM: In this paper, suggestions are offered about the appropriate use of
      hermeneutic phenomenology and grounded theory in one study. BACKGROUND: As an
      alternative to selecting only one qualitative research approach to illuminate a
      topic of interest about which little is known, two qualitative approaches could
      be used in a study. Fear of 'method slurring' may prevent this alternative being
      used. Occasionally, however, credible qualitative researchers have advocated
      using various research approaches in one study, for example using hermeneutical
      phenomenology and grounded theory in triangulation. However, if pursuing this
      direction, several advances in thinking about using qualitative research
      approaches should be considered. DISCUSSION: An experience is presented of
      deciding to use grounded theory and hermeneutic phenomenology in one study.
      Cautions, practical considerations and alternative options are offered for using
      these approaches in one study, and the implications of some other possible ways
      to 'triangulate' qualitative approaches are discussed. CONCLUSION: Different
      research approaches can be creatively and successfully used in one study if there
      has been adequate consideration of vital factors that determine if there is a
      good 'fit' of the approaches not only with the research problem and question, but
      also with each other, while also maintaining the integrity of each approach.

PMID- 16972919
TI  - Development of the client-centred care questionnaire.
AB  - AIM: This paper reports the development and testing of the Client-Centred Care
      Questionnaire, aimed at evaluating the client-centredness of professional home
      nursing care from a client perspective. BACKGROUND: Client-centred care has
      become an important theme in health care. To evaluate the client-centredness of
      care and services from a client's perspective, there is a need for measurement
      instruments. METHOD: The questionnaire was developed on the basis of a
      qualitative study into client perspectives on home nursing care. Items were
      formulated that closely followed the aspects clients mentioned as central to
      client-centred home care. A pilot study was conducted with a sample of 107
      clients in three home care organizations in 2003 and 2004. These clients had
      chronic diseases and were expected to receive care for at least another 6 months.
      The questionnaire comprises 15 items. FINDINGS: Principal components analysis and
      internal consistency analysis show strong internal consistency of the items. All
      items had strong factor loadings on one dimension, and Cronbach's alpha was 0.94.
      Clients tended to be most critical about their say in the practical arrangements
      and organization of care: which person came, how often and when? Clients of the
      three organizations differed in their perceptions of client-centredness, which
      may indicate that the questionnaire is capable of differentiating between
      respondents. CONCLUSION: The results of this pilot study are promising. The
      validity of the questionnaire needs further testing.

PMID- 16972920
TI  - Stressors in five client populations: Neuman systems model-based literature
      review.
AB  - AIM: This paper reports a literature review identifying and categorizing client
      system stressors in Neuman systems model-based studies. BACKGROUND: To date,
      literature reviews related to the Neuman systems model have focused broadly on
      all concepts of the model. The concept of stressors has been selected by the
      Neuman Systems Model Research Institute as the focus for an initial collaborative
      research project. METHOD: Cooper's five-stage integrative review method was used:
      problem formulation, data collection, data evaluation, analysis and
      interpretation, and dissemination. The Neuman systems model research literature
      from 1983 to February 2005 was searched using Fawcett's Neuman systems model
      bibliography and a follow-up review of the CINAHL database using the keywords
      'Neuman systems model' and 'stressors'. A total of 87 studies published as
      journal articles or book chapters between 1983 and 2005 were reviewed; 13 of the
      87 studies met the definition of 'stressor studies'. FINDINGS: Stressors were
      identified in five client populations: caregivers, cancer survivors, ICU patients
      in intensive care units, care receivers, and parents whose children were
      undergoing day surgery. The most common data collection method was the interview,
      and investigator-developed interview guides were most often used. Evidence of
      categorization of intra-, inter- and extra-personal stressors was present. The
      following overall stressors were identified: burden of responsibility
      (caregivers); awareness of vulnerability (cancer survivors); being overwhelmed
      (patients in intensive care units); loss of control (parents); and frustration
      with role changes (care receivers). CONCLUSIONS: These data could form the basis
      for nursing practice as well as future research within a collaborative
      environment. Given the existing body of knowledge concerning Neuman system model
      derived middle range theory concepts in the caregiver population, the middle
      range theory of caregiver role strain could be tested empirically.

PMID- 16972921
TI  - Teaching critical reflection skills for advanced mental health nursing practice:
      a deconstructive-reconstructive approach.
AB  - AIM: This paper presents a literature review conducted to establish what was
      already known about critical reflection in the nursing literature and what work
      had been done on using a critical social theory framework as the basis for
      critical reflection. BACKGROUND: Critical thinking emerged as a significant
      aspect of nursing education and practice in the late 1980s. It has been promoted
      as a means by which issues in clinical practice can be examined through a
      systematic process of exploration and reasoning. Traditionally, critical thinking
      has commonly involved an attempt to link practice with theory using a scenario or
      exemplar from practice to illustrate a practice dilemma. This process is often
      constructed as a retrospective narrative of events. This paper provides a
      deconstructive-reconstructive approach that differs from some traditional
      approaches by taking a critical social theory perspective with an emphasis on
      improving practice. METHODS: The nursing literature reviewed was accessed through
      Cumulative Index of Nursing and Allied Health Literature (CINAHL). The search was
      restricted to English language and published between 1995 and 2005. Based on
      these findings, we developed a postgraduate advanced mental health nursing
      programme. FINDINGS: There were 490 articles related to 'nursing' and 'critical
      thinking'; 34 articles related to 'nursing' and 'critical reflection'; 23
      articles related to 'nursing' and 'critical social theory'; 15 articles related
      to 'mental health nursing' and 'critical thinking'; and two articles related to
      'mental health nursing' and 'critical reflection'. In the programme we developed
      based on these findings, students were facilitated to deconstruct concepts and
      knowledge integral to their own practice. In the reconstructive phase, students
      implement a change project in clinical practice, supported by a mentor.
      CONCLUSION: The deconstructive-reconstructive approach to the development of
      critical thinking skills provides advanced practitioner with the opportunity to
      integrate practice, theory and research.

PMID- 16972922
TI  - Perceptions of Israeli student nurses regarding clinical specialties and factors
      that influence these perceptions.
AB  - AIM: This paper reports a study to determine the perceptions of baccalaureate
      nursing students towards clinical specialties and what factors influenced these
      perceptions. BACKGROUND: Previous studies have shown that nursing students enter
      their professional education with preconceived perceptions about the different
      clinical specialties in nursing. Some investigators have found that factors such
      as clinical experience influence these perceptions, but others have not. Cultural
      and social influences, especially among non-western cultures, have rarely been
      investigated. METHODS: Israeli baccalaureate nursing students were surveyed in
      their first, third and fourth years of study during the years 1998-2004. They
      were asked to rank their preferences for clinical areas related to social need,
      social prestige, level of interest in the clinical area, job choice and what
      factors influenced their decisions related to job choice. Mean ranks and
      associations between class and calendar year cohorts were calculated. RESULTS:
      Critical care was consistently ranked as the highest preference in all perception
      checklists, followed by emergency, maternity and paediatric nursing. Psychiatric,
      community and gerontological nursing were consistently found at the bottom of the
      list. High levels of association were found among students from different class
      cohorts and calendar years. Life experiences were ranked as the factor that most
      influenced career choice. CONCLUSION: Nursing students in Israel tend to perceive
      clinical areas in ways similar to other students around the world. These
      perceptions are strongly influenced by personal experiences and other personal
      contacts, most often not nursing instructors. Major changes in the local society
      seem for the most part to have little impact on these perceptions. Therefore
      there is a need for international nurse educators and recruiters to develop new,
      creative strategies to encourage nursing students to pursue careers in areas
      presently considered less popular.

PMID- 16972923
TI  - Feasibility of combining e-health for patients with e-learning for students using
      synchronous technologies.
AB  - AIM: This paper is a report of a project to introduce and evaluate methods for
      using information and communication technologies to involve academic staff,
      students, and patients in a common synchronous e-learning environment.
      BACKGROUND: Although there is no strong evidence for this, there may be benefits
      in 'efficiency' and for patients and students from shared e-learning.
      Asynchronous e-learning methods in nursing education are well-established, but
      synchronous methods have received less attention. However, if feasible, because
      they are more akin to face-to-face contact, they may be more suitable for
      patients and may provide a quicker development path for e-learning. METHOD: We
      evaluated three synchronous technologies: (1) non-commercial satellite
      interactive television (TV); (2) Internet videoconferencing; and (3) webcasting,
      through feasibility studies of 'TV-style' panel discussions on health topics and
      seminars with interaction with viewers by e-mail, inter-site research meetings
      with face-to-face interaction, user surveys and literature reviews. RESULTS:
      Interactive satellite TV required the booking of rooms with specialized receiving
      equipment. This limited accessibility contributed to the high cost per
      participant. Videoconferencing proved acceptable for cross-site research meetings
      and is proposed for joint meetings for doctoral students with overseas centres
      but has the same access issues as interactive satellite TV. Webcasting is
      accessible to most users with Internet access and provides a feasible means of
      delivery of synchronous interactive material. Reported live webcasts have had
      audiences of thousands. Presentation formats: panel discussions with mixed
      patient-professional membership and mixed patient-professional audiences were
      acceptable to participants but engaging academic staff and students was
      problematic. This may be overcome with webcasting but there may still be barriers
      such as timetabling and students' concerns about learning in the same 'live'
      environment as patients. CONCLUSIONS: Limitations in accessibility have been
      demonstrated for both satellite broadcasts and videoconferencing. Webcasting
      proved the most acceptable way of supporting a common synchronous environment.
      Having identified a feasible synchronous method we can now investigate
      hypothesized benefits for staff, students, and patients of combined e-health e
      learning.

PMID- 16972924
TI  - In response to: Brilowski G.A. & Wendler M. (2005) An evolutionary concept
      analysis of caring. Journal of Advanced Nursing 50 (6), 641-650.

PMID- 16972926
TI  - Abstracts of the European Association for Vision and Eye Research Conference.
      October 4-7 2006. Vilamoura, Portugal.

PMID- 16972935
TI  - The tragic history of AIDS in the hemophilia population, 1982-1984.

PMID- 16972936
TI  - Full evaluation of an acquired case of thrombotic thrombocytopenic purpura
      following the surgical resection of glioblastoma multiforme.

PMID- 16972937
TI  - Isoprenoid biosynthesis in plants - 2C-methyl-D-erythritol-4-phosphate synthase
      (IspC protein) of Arabidopsis thaliana.
AB  - The ispC gene of Arabidopsis thaliana was expressed in pseudomature form without
      the putative plastid-targeting sequence in a recombinant Escherichia coli strain.
      The recombinant protein was purified by affinity chromatography and was shown to
      catalyze the formation of 2C-methyl-D-erythritol 4-phosphate from 1-deoxy-D
      xylulose 5-phosphate at a rate of 5.6 micromol x min(-1) x mg(-1) (k(cat) 4.4 s(
      1)). The Michaelis constants for 1-deoxy-D-xylulose 5-phosphate and the
      cosubstrate NADPH are 132 and 30 microm, respectively. The enzyme has an absolute
      requirement for divalent metal ions, preferably Mn2+ and Mg2+, and is inhibited
      by fosmidomycin with a Ki of 85 nm. The pH optimum is 8.0. NADH can substitute
      for NADPH, albeit at a low rate (14% as compared to NADPH). The enzyme catalyzes
      the reverse reaction at a rate of 2.1 micromol x min(-1) x mg(-1).

PMID- 16972938
TI  - Multi-tasking of nonstructural gene products is required for bean yellow dwarf
      geminivirus transcriptional regulation.
AB  - Mastreviridae, of the family geminiviridae, possess a monopartite genome and are
      transmitted by leafhoppers. Bean yellow dwarf dirus (BeYDV) is a mastrevirus
      which originated from South Africa and infects dicoyledenous plants, a feature
      unusual for mastreviridae. Previously, the nonstructural proteins Rep and RepA
      were examined with respect to their independent roles in BeYDV replication. This
      was achieved by placing both gene products under independent constitutive
      promoter control and examining their effects on replication-competent constructs.
      In the current study, Rep and RepA are examined further for their roles in
      regulating BeYDV gene expression using a series of replication-incompetent
      constructs. While both Rep and RepA are found to behave as equally potent
      inhibitors of complementary-sense gene expression, they differ considerably with
      respect to their abilities to transactivate virion-sense gene expression.
      Furthermore, RepA is identified as playing more than one role in this
      transactivation process. A nuclear localization domain is identified in Rep which
      is absent in RepA, and Rep-RepA interactions are examined under in vivo
      conditions. The study concludes with an investigation into the expression
      strategies of the BeYDV capsid protein.

PMID- 16972939
TI  - Mutagenesis of hydrogenase accessory genes of Synechocystis sp. PCC 6803.
      Additional homologues of hypA and hypB are not active in hydrogenase maturation.
AB  - Genes homologous to hydrogenase accessory genes are scattered over the whole
      genome in the cyanobacterium Synechocystis sp. PCC 6803. Deletion and insertion
      mutants of hypA1 (slr1675), hypB1 (sll1432), hypC, hypD, hypE and hypF were
      constructed and showed no hydrogenase activity. Involvement of the respective
      genes in maturation of the enzyme was confirmed by complementation. Deletion of
      the additional homologues hypA2 (sll1078) and hypB2 (sll1079) had no effect on
      hydrogenase activity. Thus, hypA1 and hypB1 are specific for hydrogenase
      maturation. We suggest that hypA2 and hypB2 are involved in a different metal
      insertion process. The hydrogenase activity of DeltahypA1 and DeltahypB1 could be
      increased by the addition of nickel, suggesting that HypA1 and HypB1 are involved
      in the insertion of nickel into the active site of the enzyme. The urease
      activity of all the hypA and hypB single- and double-mutants was the same as in
      wild-type cells. Therefore, there seems to be no common function for these two
      hyp genes in hydrogenase and urease maturation in Synechocystis. Similarity
      searches in the whole genome yielded Slr1876 as the best candidate for the
      hydrogenase-specific protease. The respective deletion mutant had no hydrogenase
      activity. Deletion of hupE had no effect on hydrogenase activity but resulted in
      a mutant unable to grow in a medium containing the metal chelator
      nitrilotriacetate. Growth was resumed upon the addition of cobalt or methionine.
      Because the latter is synthesized by a cobalt-requiring enzyme in Synechocystis,
      HupE is a good candidate for a cobalt transporter in cyanobacteria.

PMID- 16972940
TI  - Crystal structures of Nipah and Hendra virus fusion core proteins.
AB  - The Nipah and Hendra viruses are highly pathogenic paramyxoviruses that recently
      emerged from flying foxes to cause serious disease outbreaks in humans and
      livestock in Australia, Malaysia, Singapore and Bangladesh. Their unique genetic
      constitution, high virulence and wide host range set them apart from other
      paramyxoviruses. These characteristics have led to their classification into the
      new genus Henpavirus within the family Paramyxoviridae and to their designation
      as Biosafety Level 4 pathogens. The fusion protein, an enveloped glycoprotein
      essential for viral entry, belongs to the family of class I fusion proteins and
      is characterized by the presence of two heptad repeat (HR) regions, HR1 and HR2.
      These two regions associate to form a fusion-active hairpin conformation that
      juxtaposes the viral and cellular membranes to facilitate membrane fusion and
      enable subsequent viral entry. The Hendra and Nipah virus fusion core proteins
      were crystallized and their structures determined to 2.2 A resolution. The Nipah
      and Hendra fusion core structures are six-helix bundles with three HR2 helices
      packed against the hydrophobic grooves on the surface of a central coiled coil
      formed by three parallel HR1 helices in an oblique antiparallel manner. Because
      of the high level of conservation in core regions, it is proposed that the Nipah
      and Hendra virus fusion cores can provide a model for membrane fusion in all
      paramyxoviruses. The relatively deep grooves on the surface of the central coiled
      coil represent a good target site for drug discovery strategies aimed at
      inhibiting viral entry by blocking hairpin formation.

PMID- 16972941
TI  - The Emery-Dreifuss muscular dystrophy associated-protein emerin is phosphorylated
      on serine 49 by protein kinase A.
AB  - Emerin is a ubiquitously expressed inner nuclear membrane protein of unknown
      function. Mutations in its gene give rise to X-linked Emery-Dreifuss muscular
      dystrophy (X-EDMD), a neuromuscular condition with an associated life-threatening
      cardiomyopathy. We have previously reported that emerin is phosphorylated in a
      cell cycle-dependent manner in human lymphoblastoid cell lines [Ellis et al.
      (1998) Aberrant intracellular targeting and cell cycle-dependent phosphorylation
      of emerin contribute to the EDMD phenotype. J. Cell Sci. 111, 781-792]. Recently,
      five residues in human emerin were identified as undergoing cell cycle-dependent
      phosphorylation using a Xenopus egg mitotic cytosol model system (Hirano et al.
      (2005) Dissociation of emerin from BAF is regulated through mitotic
      phosphorylation of emerin in a Xenopus egg cell-free system. J. Biol. Chem.280,
      39 925-39 933). In the present paper, recombinant human emerin was purified from
      a baculovirus-Sf9 heterogeneous expression system, analyzed by protein mass
      spectrometry and shown to exist in at least four different phosphorylated
      species, each of which could be dephosphorylated by treatment with alkaline
      phosphatase. Further analysis identified three phosphopeptides with m/z values of
      2191.9 and 2271.7 corresponding to the singly and doubly phosphorylated peptide
      158-DSAYQSITHYRPVSASRSS-176, and a m/z of 2396.9 corresponding to the
      phosphopeptide 47-RLSPPSSSAASSYSFSDLNSTR-68. Sequence analysis confirmed that
      residue S49 was phosphorylated and also demonstrated that this residue was
      phosphorylated in interphase. Using an in vitro protein kinase A assay, we
      observed two phospho-emerin species, one of which was phosphorylated at residue
      S49. Protein kinase A is thus the first kinase that has been identified to
      specifically phosphorylate emerin. These results improve our understanding of the
      molecular mechanisms underlying X-EDMD and point towards possible signalling
      pathways involved in regulating emerin's functions.

PMID- 16972944
TI  - Pediatric primary cutaneous marginal zone lymphoma: in association with chronic
      antihistamine use.
AB  - Primary cutaneous marginal zone lymphoma of the mucosa-associated lymphoid tissue
      predominantly occurs in adults and is rare in children. There have been no prior
      reports of this lymphoma occurring in American children. We present a case of a
      15-year-old male with a history of atopic diathesis and chronic use of
      antihistamine agents who presented with an asymptomatic lesion on his left
      forearm of 6 months duration. Because histopathological and immunohistochemical
      studies were compatible with marginal zone lymphoma, and the patient had no
      associated extracutaneous disease, the diagnosis of primary cutaneous marginal
      zone lymphoma was rendered. Based on the patient's past medical history prior to
      appearance of lesion, it was postulated that the development of lymphoma was
      associated with the ingestion of antihistamines and further propagated by his
      underlying atopic diathesis.

PMID- 16972945
TI  - Cutaneous involvement by angioimmunoblastic T-cell lymphoma: a unique histologic
      presentation, mimicking an infectious etiology.
AB  - Angioimmunoblastic T-cell lymphoma (AILT) is an aggressive peripheral T-cell
      lymphoma that is frequently accompanied by a cutaneous eruption. The cutaneous
      findings most commonly consist of a maculopapular eruption on the trunk. However,
      purpura, infiltrated or urticarial plaques, papulovesicular lesions, nodules, and
      erythroderma have also been reported. Histologic findings in the lymph node are
      characteristic, while those in the skin may show one of four patterns. Here, we
      review the previously reported histologic patterns and present a case of AILT
      involving the skin with a unique histologic appearance of necrotizing granulomas
      with abundant histiocytes and eosinophils, mimicking an infectious etiology.

PMID- 16972946
TI  - Mycosis fungoides/Sezary syndrome: report of an unusual case.
AB  - INTRODUCTION: Sezary syndrome (SS) is an uncommon form of cutaneous T cell
      lymphoma (CTCL) with a classical triad of lymphadenopathy, characteristic
      circulating lymphoma cells (Sezary cells) and erythrodermatous skin involvement
      with classical mycosis fungoides (MF)-like histological picture. CASE REPORT: A
      32-year-old woman presented with this classical triad; however, her skin
      involvement, histologically, was in the form of folliculotropic MF, rather than
      the usual classical form of MF. CONCLUSIONS: In the vast majority of cases, the
      cutaneous involvement in SS resembles conventional MF, histologically. One case
      of CD30-positive CTCL with pilotropic MF has been reported. However, English
      literature does not describe any case of SS with folliculotropic MF with typical
      immunophenotype of SS thus far. We presume that this case represents the first
      report of SS with folliculotropic MF histologically, displaying the typical CD30
      negative immunophenotype.

PMID- 16972947
TI  - Lymphocytoma cutis due to pierced earrings.
AB  - We report two cases of lymphocytoma cutis caused by pierced earrings, with the
      results of patch tests and X-ray microanalyses on electron microscopy. We
      detected zinc through scanning electron microscopy from the specimen of Case 1
      and gold and titanium through transmission electron microscopy from Case 2. This
      is the first report to demonstrate the presence of metal fragments in the lesion,
      which may suggest the remanence of metal for 20 years, bringing about persistent
      allergic reaction.

PMID- 16972948
TI  - Cutaneous leiomyosarcoma with myxoid alteration arising in a setting of multiple
      cutaneous smooth muscle neoplasms.
AB  - BACKGROUND: Cutaneous leiomyomas and leiomyosarcomas are rare tumors that
      originate from the arrector muscle of hair follicles or the smooth muscle of
      blood vessels. CASE REPORT: A 74-year-old male presented with a single,
      erythematous nodule on the left upper arm. This lesion developed within the
      excision scar of a piloleiomyoma that had been excised 3 years ago. Additionally,
      physical examination revealed a tender nodule on the right ear. RESULTS:
      Histological examination showed a cutaneous leiomyosarcoma with myxoid alteration
      on the upper arm and an angioleiomyoma on the right ear. CONCLUSION: Myxoid
      leiomyosarcomas have exclusively been reported in the uterus and gastrointestinal
      tract, but not in the skin. Here, we describe a case of cutaneous leiomyosarcoma
      with myxoid alteration that developed in the excision scar of a piloleiomyoma and
      was accompanied by a cutaneous angioleiomyoma in a different location.

PMID- 16972949
TI  - CD99 immunoreactivity in atypical fibroxanthoma and pleomorphic malignant fibrous
      histiocytoma: a useful diagnostic marker.
AB  - Atypical fibroxanthoma (AFX), a benign lesion, and pleomorphic malignant fibrous
      histiocytoma (MFH) are thought to represent points along the same neoplastic
      spectrum but with different prognoses and treatments. Diagnosis based on
      histology and clinical parameters alone is sometimes difficult, and a reliable
      cost-effective immunohistochemical marker to help distinguish these lesions would
      be beneficial. The diagnosis of AFX or MFH was based upon published clinical and
      microscopic criteria. Formalin-fixed, paraffin-embedded tissues of 17 cases of
      AFX and 26 cases of MFH were immunostained with monoclonal antibody to CD99. For
      all cases, CD99 expression was scored on a four-tiered scale: negative, weak
      (1+), moderate (2+), or strong (3+). Two pathologists blinded to tumor diagnoses
      and type of immunostain evaluated each case independently. The interobserver
      correlation coefficient was calculated. Seventeen patients with AFX (16 males and
      one female; mean age = 79) and 26 patients with MFH (16 males and 10 females;
      mean age = 60) were included. AFX lesions were from the head and the face, mean
      size = 1.5 cm, and MFH lesions were from the head, the neck, the trunk, and the
      upper/lower extremities, mean size = 5.2 cm. The 17 cases of AFX demonstrated
      moderate or strong (2 to 3+) immunoreactivity with CD99, compared to nine of 26
      (35%) MFH cases (chi-square = 18.38; p < 0.001; interobserver correlation
      coefficient = 0.83). Of these, 16 of 17 (94%) AFX cases stained diffusely with
      CD99, while only four of 26 (15%) MFH cases stained diffusely. Control slides
      were adequate. Our study demonstrated that CD99 can help distinguish AFX from
      MFH, in addition to other immunohistochemistry as well as clinical and histologic
      criteria.

PMID- 16972950
TI  - Desmoplastic cutaneous leiomyosarcoma: case report and review of the literature.
AB  - We report the case of a 51-year-old man with an asymptomatic indurated plaque on
      the chest wall that was surgically excised and submitted for histopathological
      examination. Microscopically, the dermis was occupied by a neoplastic process
      with spindle-shaped cells arranged in longitudinal fascicles with cytologic
      atypia; the abundant sclerotic stroma was composed of hyaline material. Tumoral
      cells showed immunohistochemical reactivity to smooth muscle markers. The
      diagnosis was desmoplastic leiomyosarcoma of the skin. This unusual entity is
      identified and discussed, and we review the literature.

PMID- 16972951
TI  - Atypical primary carcinoid tumour of the skin.
AB  - We present a new case of a primary carcinoid tumour of the skin. The mitotic
      index (4/10 HPF) warrants classification of this case as atypical. The patient
      was a 58-year-old woman with a 1-year history of a mass on the scalp. Literature
      review showed this to be only the seventh case of primary carcinoid tumour of the
      skin. Importantly, the evolution has been favourable in all seven tumours, with a
      mean follow-up of 2.5 years for the previous six cases. Although the number of
      cases is too small to draw definitive conclusions, information to date suggests
      that this type of tumour can be expected to have a benign behaviour, despite the
      presence in some cases of criteria suggestive of uncertainty, such as the
      presence of mitosis.

PMID- 16972952
TI  - Cutaneous mixed tumor with lipomatous stroma.
AB  - AIM: Mixed tumors are usually composed of two components, one epithelial and the
      other mesenchymal. The latter component is commonly myxoid or myxochondroid; a
      massively lipomatous stroma is very unusual. To date, only two cases of mixed
      tumor of the skin have been reported with this type of stroma. METHODS AND
      RESULTS: We report the case of a 61-year-old man with a mixed tumor situated on
      the hand, an unusual site for these tumors, with over 90% of the tumor composed
      of adipose tissue. The tumor was a well-circumscribed, 4.5-cm mass, with the
      gross appearance of a lipoma. The lipomatous stroma contained nests and ribbons
      of epithelial cells, with occasional tubular structures, surrounded by a scarce
      amount of fibromyxoid tissue. Immunohistochemical study showed findings similar
      to those seen in classic mixed tumors. CONCLUSION: Together with a few other
      cases in the skin and parotid gland, this report shows how massive adipose
      differentiation can arise in a mixed tumor of the skin.

PMID- 16972953
TI  - An unusual presentation of periocular Merkel cell carcinoma.
AB  - AIM: Merkel cell carcinoma (MCC) is an uncommon but potentially aggressive tumor.
      We describe a rare presentation of MMC of the upper lid. METHODS: A 63-year-old
      male presented with a 3-month history of right upper lid fullness. Examination
      revealed a large multinodular mass protruding into the conjunctival aspect of the
      eyelid. An enlarged right submandibular lymph node was also noted. RESULTS: An
      incisional biopsy was suggestive of MCC. Staged surgical excision with rapid
      paraffin sections was performed. The tumor cells were seen invading the tarsal
      plate and adjacent to the palpebral conjunctiva but not into the epidermis. MCC
      was confirmed using immunohistochemical stains and neuroendocrine markers
      (cytokeratins Cam 5.2, AE1/3, CK20, chromogranin, synaptophysin, and Leu 7). The
      lymph node biopsy was also confirmed as metastatic MCC. The patient was treated
      with postsurgical chemotherapy and radiotherapy, with no recurrence during a 6
      months follow-up period. CONCLUSION: Although uncommon, periocular MCC may
      present as an atypical conjunctival multinodular mass.

PMID- 16972954
TI  - Seborrheic keratosis with pseudorosettes and adamantinoid seborrheic keratosis:
      two new histopathologic variants.
AB  - AIMS: Seborrheic keratoses are the most common benign cutaneous neoplasms in
      adult and middle-age patients. There are six distinctive histopathologic variants
      of seborrheic keratosis, namely, acanthotic or solid, reticulated or adenoid,
      hyperkeratotic or papillomatous, clonal or nested, irritated and inflamed.
      METHODS: We report two additional histopathologic variants of seborrheic
      keratosis. RESULTS: One lesion showed abundant intercellular mucin, closely
      resembling to adamantinoma, and therefore was named adamantinoid seborrheic
      keratosis. The other one exhibited a peculiar distribution of the basaloid
      keratinocytes, which were arranged radially around small central spaces,
      resulting in pseudorosette formation. DISCUSSION: To our knowledge, these two
      histopathologic variants of seborrheic keratosis have been not previously
      described in the literature.

PMID- 16972955
TI  - KSHV/HHV8-associated primary cutaneous plasmablastic lymphoma in a patient with
      Castleman's disease and Kaposi's sarcoma.
AB  - We report a unique case of Kaposi's sarcoma (KS)-associated herpesvirus
      (KSHV)/human herpesvirus (HHV)8-associated lymphoma in a 56-year-old man with a
      history of acquired immune deficiency syndrome, Castleman's disease, KS, and
      idiopathic thrombocytopenic purpura. Three months following the diagnosis of KS
      affecting a left cervical lymph node and Castleman's disease with bone marrow
      involvement, he presented with a subcutaneous, tender lesion on his left arm. A
      skin biopsy demonstrated a superficial and deep, interstitial-nodular infiltrate
      of severely atypical lymphoid cells showing plasmacytoid features, numerous
      mitotic figures, and frequent individual apoptotic tumor cells. The morphologic
      features were those of plasmablastic lymphoma (PBL). Immunohistochemical study
      showed that the lymphoma cells strongly expressed CD45, CD30, and KSHV/HHV8
      latency-associated nuclear antigen. KSHV/HHV8 was also detected in the biopsy
      sections of the patient's KS and Castleman's disease. Epstein-Barr virus in situ
      hybridization was diffusely positive. In situ hybridization demonstrated kappa
      light chain restriction. Although KSHV/HHV8 has been individually associated with
      KS, Castleman's disease, and PBL, this appears to be the first reported case in
      which all three entities were present simultaneously in one person, suggesting a
      critical role of KSHV/HHV8 as a common denominator in the pathogenesis of these
      diseases.

PMID- 16972956
TI  - Is confluent and reticulated papillomatosis without papillomatosis early or late
      stage of confluent and reticulated papillomatosis?
AB  - The histologic findings of confluent and reticulated papillomatosis include
      papillomatosis, hyperkeratosis, and minimal or no acanthosis. We present a
      patient with the clinical findings of confluent and reticulated papillomatosis
      who responded dramatically to azithromycin, but histologic examination did not
      reveal papillomatosis. We observed invagination of basket-weave hyperkeratosis
      through the epidermis. We considered this finding may give a clue for the
      diagnosis of confluent and reticulated papillomatosis.

PMID- 16972957
TI  - Lipodermatosclerosis as a form of vascular compromise-associated radiation recall
      dermatitis: case report and a review of literature.
AB  - Lipodermatosclerosis (LDS) is a prototypic ischemic dermopathy that is most
      commonly associated with venous insufficiency. There have been no prior reports
      describing LDS as a form of radiation recall dermatitis (RRD). We present a case
      of a 47-year-old female affected by squamous cell carcinoma of the anus who
      underwent irradiation and subsequent chemotherapy with 5-fluorouracil and
      cisplatin. She then developed tender, erythematous, indurated plaques on skin of
      the buttocks, corresponding closely to one of the previous radiotherapy fields.
      As histopathological studies were compatible with LDS and the skin eruption
      coincided with drug intake 3 months after radiotherapy, the diagnosis of RRD with
      LDS features was rendered. This is the first case providing evidence of the
      causative role of 5-fluorouracil and cisplatin in potentially inducing RRD.

PMID- 16972958
TI  - Calcinosis cutis: a complication of intravenous administration of calcium
      glucanate.
AB  - Calcinosis cutis, the deposition of calcium in the dermis, can be dystrophic,
      metastatic, iatrogenic, or idiopathic. Here, we describe a case of iatrogenic
      calcinosis cutis secondary to extravasation of an intravenous calcium-containing
      solution in a child. We also review the literature regarding the pathogenic
      mechanisms involved in the development of calcinosis cutis after extravasation
      injuries. While iatrogenic calcinosis cutis is generally a benign entity, it is
      important to recognize its unique clinical and histopathologic presentation to
      avoid complications from misdiagnosis.

PMID- 16972959
TI  - Splitting hairs: the 'hamburger sign' in trichotillomania.
AB  - BACKGROUND: A 43-year-old male presented with the clinical findings of patchy
      alopecia that contained persistent hair and re-growth of hairs of various
      lengths, consistent with trichotillomania. A biopsy was performed to confirm the
      diagnosis.. RESULTS: Histologic evaluation revealed findings consistent with
      trichotillomania, including trichomalacia. Several hair shafts also showed a
      vertically oriented split, which contained proteinaceous material and
      erythrocytes. Morphologically, these were reminiscent of a hamburger within a
      bun. CONCLUSIONS: The unusual finding reported in this case has not been
      previously reported. The "hamburger bun sign" provides an additional clue to
      traumatic injury in the evaluation of biopsies for trichotillomania.

PMID- 16972960
TI  - Global implementation of WHO clinical guidelines to improve child survival: the
      need for collaboration, resources and action.

PMID- 16972961
TI  - Critical appraisal of the management of severe malnutrition: 1. Epidemiology and
      treatment guidelines.
AB  - Hospital case-fatality rates for severe malnutrition in the developing world
      remain high, particularly in Africa where they have not changed much over recent
      decades. In an effort to improve case management, WHO has developed treatment
      guidelines. The aim of this review is to critically appraise the evidence for the
      guidelines and review important recent advances in the management of severe
      malnutrition. We conclude that not only is the evidence base deficient, but also
      the external generalisability of even good-quality studies is seriously
      compromised by the great variability in clinical practice between regions and
      types of health facilities in the developing world, which is much greater than
      between developed countries. The diagnosis of severe wasting is complicated by
      the dramatic change in reference standards (from CDC/WHO 1978 to CDC 2000 in
      EpiNut) and also by difficulties in accurate measurement of length. Although
      following treatment guidelines has resulted in improved outcomes, there is
      evidence against the statement that case-fatality rates (particularly in African
      hospitals) can be reduced below 5% and that higher rates are proof of poor
      practice, because there is wide variation in severity of illness factors. The
      practice of prolonged hospital treatment of severe malnutrition until wasting
      and/or oedema has resolved is being replaced by shorter hospital stays combined
      with outpatient or community follow-up because of advances in dietary management
      outside of hospital.

PMID- 16972962
TI  - Critical appraisal of the management of severe malnutrition: 2. Dietary
      management.
AB  - In the dietary management of severe acute malnutrition in children, there is
      evidence to support the WHO Manual's protocol of cautious feeding of a low energy
      and protein formula with small frequent feeds in the initial phase of treatment,
      particularly in kwashiorkor. However, this initial milk diet (WHO F-75) might
      benefit from increasing the sulphur amino acid, phosphorus and potassium content
      and reducing the lactose content, but further studies are needed. Careful tube
      feeding results in faster initial recovery and weight gain, but has a significant
      risk of aspiration in poorly supervised settings. Ready-to-use therapeutic food
      is an important recent advance in the dietary management of malnutrition in
      ambulatory settings, allowing more effective prevention programmes and earlier
      discharge from hospital where community follow-up is available. It should be
      included in future protocols. There is very good evidence on the use of
      micronutrients such as zinc, and preliminary evidence suggests that smaller doses
      of daily vitamin A are preferable to a single large dose on admission for severe
      malnutrition.

PMID- 16972963
TI  - Critical appraisal of the management of severe malnutrition: 3. Complications.
AB  - The high case-fatality of severe malnutrition is due to infections, dehydration,
      electrolyte disturbances and heart failure. We focus on the evidence about
      managing these complications of severe malnutrition. Signs of circulatory
      collapse in severely malnourished children should be treated with intravenous or
      bone marrow infusion of Ringer's lactate with additional dextrose and potassium
      at a rate 20-40 mL/kg fast with close monitoring of vital signs. Recommendations
      for slow or restricted fluids in the face of shock are unsafe, and hypotonic or
      maintenance solutions must be avoided to prevent hyponatraemia. However, the
      evidence that severely malnourished children do not tolerate excessive fluid
      administration is good, so caution must be exercised with regards to fluids in
      the initial phase of treatment. There is also good evidence that wide spectrum
      antibiotics need to be given empirically for severe malnutrition to prevent the
      otherwise unavoidable early mortality. There is a need for improved protocols for
      tuberculosis diagnosis, HIV management and treatment of infants under 6 months
      with severe malnutrition. The contribution of environmental enteropathy to poor
      growth and nutrition during the weaning period means that there should be more
      priority on improving environmental health, particularly better hygiene and less
      overcrowding. A T-cell mediated enteropathy contributes to growth failure and
      malnutrition, and it is related to environmental contamination of enteric
      organisms in the weaning period rather than allergic responses.

PMID- 16972964
TI  - Critical appraisal of the management of severe malnutrition: 4. Implications for
      Aboriginal child health in northern Australia.
AB  - The main implications of this review for the treatment of malnourished Australian
      Aboriginal children in northern Australia are that the emphasis needs to change
      from hospital case management with enteral tube-feeding to improved community
      management with a focus on environmental health (e.g. housing, hygiene and
      overcrowding) and child care issues.

PMID- 16972965
TI  - Treatment burden and health-related quality of life of children with diabetes,
      cystic fibrosis and asthma.
AB  - AIM: To identify the time required by children with cystic fibrosis (CF),
      diabetes or asthma to complete daily treatment tasks and the hassle they
      experienced when completing these tasks. To compare parent and child reports of
      daily treatment time and hassle. To investigate the relationship between
      treatment time and hassle, and (i) children's health-related quality of life
      (HRQL); and (ii) disease severity. METHODS: 160 children aged 10-16 years with
      CF, type 1 diabetes, or asthma were followed over a 2-year period. Information
      about children's treatment time and hassle, and their HRQL was obtained from
      parents and children at baseline, 1-year and 2-year follow-up assessments.
      RESULTS: On average, children with CF reported spending 74.6 +/- 57.0 min
      completing treatment tasks, children with diabetes spent 56.9 +/- 27.8 min and
      children with asthma spent 6.4 +/- 9.3 min. Parents reported that children spent
      less time that was reported by their children. Over the two years, parent and
      child reports describing treatment time for children with CF did not vary
      significantly (P = 0.3). Treatment time for children with diabetes increased (P =
      0.02) whereas that for children with asthma reduced (P = 0.001). The level of
      hassle experienced by children when completing individual treatment tasks was low
      for all three conditions. There was no significant relationship between treatment
      time and children's HRQL. CONCLUSION: Children with CF or diabetes spent a
      substantial amount of time each day completing the treatment tasks. Although this
      was not related to HRQL, it could impact the ability to comply with complex and
      all home-based-therapies for some children.

PMID- 16972966
TI  - Pharmacokinetic profile of once daily intravenous tobramycin in children with
      cystic fibrosis.
AB  - AIM: Once-daily tobramycin in patients with cystic fibrosis (CF) is a more
      convenient dosing regimen than thrice daily dosing. There are limited data on the
      pharmacokinetic (PK) profile for once-daily tobramycin in patients with CF. The
      aim of this study was to define the PK parameters for once-daily tobramycin in
      children with CF and develop an algorithm for therapeutic drug monitoring dosing.
      METHODS: CF patients admitted to hospital were commenced on once-daily
      intravenous tobramycin (12 mg/kg/day) and ticarcillin/clavulinic acid. Serum
      tobramycin levels were taken at 30 min, 2-4 h and 12 h post dose. Data points for
      the PK model included: age, sex, weight, tobramycin dose, time of tobramycin
      doses and levels, tobramycin levels. WinNonMix was used to obtain the PK
      parameters. RESULTS: Forty-four children with 86 admissions who were aged 9
      months-20 years were included. A one-compartment intravenous infusion model with
      first order elimination kinetics produced the best model. Population parameters
      were: volume of distribution (V(d)) = 0.267 L/kg (95% confidence interval (CL)
      0.260-0.272), clearance (CL) 0.103 L/kg/h (95% CI 0.098-0.107) and half-life
      (t(1/2)) 1.82 (95% CI 1.77-1.88) h. Once the population model was established
      post hoc analysis was used to calculate individual subject predictions. Plots of
      individual prediction curves agreed well with observed values. CONCLUSION: This
      study has established an algorithm for routine monitoring of once-daily
      tobramycin in children with CF. Satisfactory serum levels of tobramycin were
      obtained with a dose of 12 mg/kg/day and a regimen algorithm that uses only one
      measurement to monitor the plasma concentration is suggested.

PMID- 16972967
TI  - Post-neonatally acquired cerebral palsy in Victoria, Australia, 1970-1999.
AB  - AIM: To use the information from a population-based cerebral palsy register to
      describe post-neonatally acquired cerebral palsy, to determine trends over time
      and relate any aetiological trends to community preventative measures. METHODS:
      Data on cases of post-neonatally acquired cerebral palsy, between the birth years
      1970 and 1999, were generated from the Victorian Cerebral Palsy Register.
      Distributions, rates and trends over time were calculated for the entire cohort
      and for subgroups according to gender, age at acquisition, aetiology, gestation
      at delivery, birthweight, maternal age at delivery and parity. RESULTS: 339 cases
      were found with post-neonatally acquired cerebral palsy, accounting for 10.7% of
      all cerebral palsy and giving an overall rate of 1.98/10 000 live births. There
      was a statistically significant fall in the overall rate of post-neonatally
      acquired cerebral palsy (P = 0.001) over the study period. Significant falls were
      seen in post-neonatal cerebral palsy due to infection, traumatic head injury and
      hypoxia and other acute encephalopathies, but not cerebrovascular accidents.
      CONCLUSION: A large proportion of post-neonatally acquired cerebral palsy is
      preventable. While the reported decline in cases in Victoria is encouraging, it
      will be important to monitor these trends over time, and continue public health
      measures to further reduce preventable causes.

PMID- 16972968
TI  - Antibiotic prescribing for childhood febrile illness by primary care doctors in
      Malaysia.
AB  - AIM: Fever in children, a mostly benign and self-limiting illness, is often
      viewed with consternation by the care givers. It results in early consultation
      and excessive use of antipyretics and antibiotics. In this study, we document the
      prescribing practice of doctors from three primary care settings in Malaysia and
      identify the predictors of antibiotic prescription. METHODS: Interview of care
      givers bringing febrile children (age </= 12 years) to three primary care
      settings: public primary care clinics, private general practice clinics and a
      university-based primary care clinic. RESULTS: Data from 649 children were
      analysed. Mean age of children 4.1 years and 55% were boys. One-third of the
      children had prior consultation for the same episode of fever. About 80% of the
      febrile children were diagnosed to have upper respiratory tract infection, viral
      fever and gastroenteritis. Overall antibiotic prescribing rate was 36.6% (public
      primary care clinic 26.8%, private general practice clinic 70.0% and university
      based primary care clinic 32.2%). Independent predictors of antibiotic
      prescription were: clinic setting, longer duration of fever (>7 days), higher
      temperature (>38 degrees C) and the diagnosis of upper respiratory tract
      infections. After controlling for demographic and clinical factors, antibiotic
      prescription in private general practice clinic was seven times higher than
      public primary care clinic (odds ratio 7.1, 95% confidence interval 4.0-12.7),
      and 1.6 times higher than university-based primary care clinic (odds ratio 1.6,
      95% confidence interval 1.0-2.5). CONCLUSION: Differences in the patients'
      demographic and clinical characteristics could not adequately explain the high
      antibiotic prescribing rate in private general practice clinics. This
      inappropriately high antibiotic prescribing for febrile children in private
      general practice clinics is a suitable target for future intervention.

PMID- 16972969
TI  - Is elective surgery traumatic for children and their parents?
AB  - AIM: The emotional consequences of elective surgery to children and to their
      parents have not been sufficiently studied. The aim of the present study was to
      prospectively assess the prevalence and severity of post-traumatic, anxiety and
      depressive symptoms in this population. METHODS: Forty children and adolescents
      consecutively admitted for elective surgery in a general hospital participated in
      the study. Their parents were also assessed. The assessments were made on the day
      of admission and surgery, and 1 and 6 months after the surgery. RESULTS: Minor
      post-traumatic symptoms of the children were noted at the first and second
      assessments, decreasing significantly at the 6-month assessment. Further, the
      prevalence of children with elevated post-traumatic symptoms decreased
      significantly between the first and second assessments. Parents scored highest
      for anxiety and depression at the first assessment. Their symptoms, however,
      decreased significantly within 1 month. A significant decrease between the first
      and second assessments was also noted in the prevalence of parents with elevated
      anxiety symptoms. At the 1- and 6-month follow-up assessments, there was a
      significant correlation between the children's symptoms and their parents'.
      CONCLUSION: Mild post-traumatic symptoms may accompany paediatric elective
      surgery and persist for at least 1 month. Parents may also manifest anxiety and
      depressive symptoms, which may diminish earlier, that is, immediately after the
      surgery or within 1 month.

PMID- 16972970
TI  - Sleep architecture in children with adenoidal hypertrophy.
AB  - AIM: Adenoidal hypertrophy (AH) in children is associated with obstructive
      manifestations like mouth breathing, snoring. Unfortunately, little is known
      regarding sleep architecture of AH in children. The purpose of this study was
      therefore undertaken to investigate the polysomnographic variables in children
      with AH. METHOD: 47 children with AH and 11 controls underwent nocturnal
      polysomnography. Sleep was scored manually according to the standard set by
      Rechtschaffen. RESULTS: In AH, stage 1 sleep percentage and rapid eye movement
      (REM) latency were increased significantly, while the sleep percentage of stage 2
      and REM was decreased remarkably compared with that of controls. Arousal index in
      AH was much more higher than that in controls. Arousal index in REM sleep was
      higher than that in non-rapid eye movement (NREM) sleep in AH, but the number of
      arousals in REM sleep was lower than that in NREM sleep. Hypopnea events were the
      most common type of respiratory events, followed by obstructive events in AH and
      controls. Apnea/hypopnea index in AH was higher in comparison to controls. No
      significant difference was found between the children with AH and controls in
      SaO(2) nadir (%) and base mean SaO(2) (%). Apnea/hypopnea index was related to
      hypopnea arousal in REM sleep and hypoxemia arousal in NREM sleep. CONCLUSION: AH
      is predominantly characterised by a hypopnea with little obstruction in children.
      Our results clearly and for the first time demonstrated that sleep architecture
      was abnormal in children with AH. We therefore speculate that hypopnea arousal in
      REM sleep and hypoxemia arousal in NREM sleep may play an important role in the
      course of respiratory disturbance.

PMID- 16972971
TI  - Effect of multiple birth on infant mortality in Bangladesh.
AB  - AIM: Levels of infant and child mortality in many developing countries remain
      unacceptably high, and they are disproportionably higher among high-risk groups
      such as newborn and infant of multiple births, particularly in countries where
      advanced medical cares are available only at regional referral levels with
      limited access by the poor rural women and children. This study examined the
      relationship between high-risk infant of multiple birth and infant mortality in
      Bangladesh. METHODS: The analysis uses information on 7001 childbirths in 5 years
      preceding the 2004 Bangladesh Demographic and Health Survey to examine the
      relationship between multiple birth and infant mortality using multivariate
      analysis, controlling for child's sex, birth order, prenatal care, delivery
      assistance; mother's age at child birth, nutritional status, education level;
      household living conditions and several other risk factors. RESULTS: Results
      indicate that children born multiple birth were more than six-times as likely to
      die during infancy as those born singletons (hazard ratio = 6.51; 95% confidence
      interval: 4.10, 10.36). Controlling for all other risk factors does not change
      the strength and direction of the relationship (hazard ratio = 6.18; 95%
      confidence interval: 3.65, 10.46). Receiving prenatal care and access to safe
      drinking water are associated with lower risk. CONCLUSION: Multiple births are
      strongly negatively associated with infant survival in Bangladesh independent of
      other risk factors. This evidence suggests that improving maternal and child
      health at the community level, screening for high-risk pregnancies and making
      referral services for these conditions more accessible to the rural women and
      children will be key to improving child survival in Bangladesh.

PMID- 16972972
TI  - Effects of extremely early enteral feeding on plasma glicentin levels in very-low
      birthweight infants.
AB  - AIM: Glicentin, an active component of enteroglucagon, is considered to have a
      significant trophic action on the intestinal mucosa. We examined the effects of
      extremely early enteral feedings on the postnatal and postprandial changes in
      plasma glicentin levels in very-low-birthweight (VLBW) infants. METHODS: We
      measured the plasma glicentin concentrations before and after feedings at 1 or 2
      days, 5 or 6 days and 14 days after birth in 21 VLBW infants. The subjects were
      randomly divided into an extremely early feeding group, which was started on
      breast milk within 24 h after birth, and a control group, which was started on
      breast milk more than 24 h after birth. RESULTS: Plasma basal concentrations of
      glicentin at 5 or 6 days and at 14 days after birth were significantly higher
      than those at 1 or 2 days after birth in the early feeding group. The basal
      glicentin level at 14 days after birth was significantly higher than that at 1 or
      2 days. The basal levels at 5 or 6 days and at 14 days after birth in the early
      feeding group were significantly higher than those in the control group. Plasma
      glicentin concentrations after feeding were significantly higher than those
      before feeding at 5 or 6 days and 14 days after birth in the early feeding group,
      but those levels were significantly higher only at 14 days after birth in the
      control group. CONCLUSION: Our results suggest that extremely early enteral
      feedings may play an important role in the development of glicentin secretion and
      intestinal mucosal growth in the early period of life in VLBW infants.

PMID- 16972973
TI  - Intravenous frusemide for transient tachypnoea of the newborn: a randomised
      controlled trial.
AB  - AIM: To investigate the effect of intravenous frusemide on the course of
      transient tachypnoea of the newborn (TTN). METHODS: Fifty term infant with TTN
      were randomised at the time of diagnosis to receive either intravenous frusemide
      2 mg/kg or saline placebo. Outcomes assessed included duration of supplemental
      oxygen requirement, the period of tachypnoea, time to discharge from hospital and
      weight loss in the first 24 h of life and before discharge. RESULTS: The two
      groups were similar with respect to sex, birthweight, mode of delivery and age at
      presentation. The study group lost significantly more weight in the first 24 h
      after birth. There were no significant differences between the two groups in the
      duration of oxygen requirements, the period of tachypnoea and the time to
      hospital discharge. CONCLUSION: A single dose of intravenous frusemide (2 mg/kg)
      does not improve the clinical course of TTN. This finding suggests that either
      frusemide is not effective in promoting resorption of lung fluid or factors other
      than delayed resorption of this fluid contribute to the pathogenesis of TTN.

PMID- 16972974
TI  - Safety and efficacy of blood glucose management practices at a diabetes camp.
AB  - AIM: Camps are an important part of diabetic management in children yet data on
      the safety and efficacy of camps are limited. We assessed the safety and efficacy
      of blood glucose management guidelines at summer camps for diabetic children.
      METHODS: Consistent management guidelines were implemented during 10 consecutive
      diabetes camps held in the same facility between 1998 and 2002. Using the entire
      sample of campers aged 9-13 years, we analysed insulin dosage alterations, the
      frequency of hypoglycaemia (<4 mmol/L), hyperglycaemia (>15 mmol/L) and ketosis
      and evaluated our overnight management guidelines. The effects of sex, year, age,
      insulin regimen and duration of diagnosis on hypoglycaemia frequency were
      determined. RESULTS: Mean insulin doses decreased 19.2% (95% confidence interval
      16.9-21.6%) by the last day of camp (day 6) relative to the day prior to camp.
      Mean blood glucose levels were 11.4 mmol/L before breakfast and the main evening
      meal, 11.3 mmol/L before bed, 10.8 mmol/L at midnight and 9.4 mmol/L at 3 am. Of
      the 10 839 readings analysed, 984 (9.1%) were below 4 mmol/L (0.5 per camper/day)
      with no clinical grade 3 (seizure or coma) hypoglycaemia. Hypoglycaemia frequency
      was independent of sex, year, age, insulin regimen and duration of diagnosis (all
      P > 0.05). There were 2570 (23.7%) readings above 15 mmol/L (1.4 per camper/day)
      but only 42 (0.4%) were associated with significant ketosis. CONCLUSION: Children
      at diabetes camps experience considerable blood glucose variability; however, the
      careful application of monitoring and management guidelines can avoid serious
      adverse events.

PMID- 16972975
TI  - Vaginal foreign body in childhood: A multidisciplinary approach.
AB  - A 5-year-old girl referred to our division for evaluation of persisting foul
      smelling brown vaginal discharge with pruritus for over 2 years, not
      corresponding to antibiotic therapy. Transabdominal ultrasound identified a
      heterogeneous mass intensely fixed in the upper third of vaginal wall.
      Vaginography revealed a filling defect in the upper part of vagina, confirming
      the diagnosis of an intravaginal foreign body. The foreign body was grasped and
      removed by traction; it turned out to be a thin double-wrapped piece of sponge.
      Psychological assessment of the girl was undertaken, in order to illuminate the
      potential of an underlying emotional and behavioural problem and revealed the
      existence of psychological disturbances mostly affecting social competence and
      adaptiveness.

PMID- 16972976
TI  - 11beta-hydroxylase deficiency masked by alternative medicines.
AB  - A 3.5-year-old Vietnamese boy presented with precocious pseudopuberty,
      hypertension and a skin rash that was treated with Vietnamese medications for 6
      weeks, with resolution. Serum androgen levels were prepubertal, adrenal
      ultrasound was normal but a large unknown abnormal peak was detected in the urine
      steroid profile. Cessation of medications disclosed elevation of plasma androgen
      and 11-deoxycortisol levels. The unidentified urine steroid profile peak
      disappeared and a tetrahydro-11-deoxycortisol peak was detected. This patient
      represents a difficult and challenging diagnosis of 11beta-hydroxylase
      deficiency. Careful evaluation of history and physical finding in the presence of
      apparent biochemistry discrepancy resulted in a correct diagnosis.

PMID- 16972977
TI  - Insulin-induced oedema in children and adolescents.
AB  - Oedema is an uncommon complication of insulin therapy, which has only rarely been
      reported in childhood. We describe a case of a 12-year-old girl with newly
      diagnosed type 1 diabetes, who presented with oedema of the lower extremities and
      periorbitally, one day after the initiation of insulin treatment. Other causes of
      oedema were excluded. Following administration of frusemide, oedema resolved
      within ten days. An extended review of the literature revealed only nine cases of
      insulin-induced oedema in children and adolescents aged </=16 years. In
      conclusion, insulin-induced oedema should be considered during the introduction
      of insulin therapy in children and adolescents with newly diagnosed type 1
      diabetes. Loop diuretics and ephedrine may be beneficial when spontaneous
      resolution does not occur.

PMID- 16972978
TI  - Biliary colic and sonographic evidence of pseudocholelithiasos 36 h after
      treatment with ceftriaxone.

PMID- 16972979
TI  - Galactosaemia presenting as bedside hyperglycaemia.

PMID- 16972980
TI  - Trend of paediatric HIV/AIDS cases in a tertiary care hospital in Delhi.

PMID- 16972981
TI  - Different outcome of allogeneic transplantation in myelofibrosis using
      conventional or reduced-intensity conditioning regimens.
AB  - Allogeneic haematopoietic stem cell transplantation remains the only curative
      treatment of myelofibrosis with myeloid metaplasia (MMM). Previous reports have
      indicated significant treatment-related mortality (TRM) for patients transplanted
      after myeloablative conditioning but superior survival has been reported after
      reduced-intensity conditioning (RIC). We report the results of a survey of all
      allogeneic transplantations for MMM performed in Sweden at six transplant units
      between 1982 and 2004. Twenty-seven patients were transplanted; 17 with a
      myeloablative conditioning regimen and 10 with RIC. The median age was 50 years
      (5-63 years) at transplantation. After a median follow up of 55 months, 20
      patients are alive. TRM was 10% in the RIC group and 30% in the myeloablative
      group. There was no difference in survival for high or low-risk patients
      according to Cervantes score or between sibling and unrelated donor
      transplantations.

PMID- 16972982
TI  - Significant increase of glycolytic flux in Torulopsis glabrata by inhibition of
      oxidative phosphorylation.
AB  - This study was aimed at increasing the glycolytic flux of the multivitamin
      auxotrophic yeast Torulopsis glabrata by disturbing oxidative phosphorylation. We
      examined two different strategies to impede oxidative phosphorylation. The first
      strategy was disruption of the activity of the electron transfer chain (ETC), by
      either of two approaches. One was separately adding, at 10 mg L1, specific
      inhibitors of complex I (rotenone) or of the bc1 complex (antimycin A) to the
      culture broth of T. glabrata CCTCC M202019, which resulted in significantly
      decreased intracellular ATP levels (43% and 27.7%) and significantly increased
      rates of glucose consumption (qs) and pyruvate production (qp); another approach
      was breeding a respiratory-deficient mutant RD-16, in which cytochromes aa3 and b
      in the ETC were deleted after ethidium bromide mutagenesis, to reduce the ETC
      activity constitutively. The second strategy was inhibiting F0F1-ATP synthase
      with 0.05 mM oligomycin. Also, a neomycin-resistant mutant with 65% decreased
      F0F1-ATPase activity was studied. With the two strategies, the specific activity
      of phosphofructokinase (R2=0.9971), the average specific glucose consumption rate
      (R2=0.9967) and the average specific pyruvate production rate (R2=0.965) were
      closely correlated with the intracellular ATP level, all of them being increased
      at a lower intracellular ATP level.

PMID- 16972983
TI  - Biochemical characterization and inhibitor discovery of shikimate dehydrogenase
      from Helicobacter pylori.
AB  - Shikimate dehydrogenase (SDH) is the fourth enzyme involved in the shikimate
      pathway. It catalyzes the NADPH-dependent reduction of 3-dehydroshikimate to
      shikimate, and has been developed as a promising target for the discovery of
      antimicrobial agent. In this report, we identified a new aroE gene encoding SDH
      from Helicobacter pylori strain SS1. The recombinant H. pylori shikimate
      dehydrogenase (HpSDH) was cloned, expressed, and purified in Escherichia coli
      system. The enzymatic characterization of HpSDH demonstrates its activity with
      k(cat) of 7.7 s(-1) and K(m) of 0.148 mm toward shikimate, k(cat) of 7.1 s(-1)
      and K(m) of 0.182 mm toward NADP, k(cat) of 5.2 s(-1) and K(m) of 2.9 mm toward
      NAD. The optimum pH of the enzyme activity is between 8.0 and 9.0, and the
      optimum temperature is around 60 degrees C. Using high throughput screening
      against our laboratory chemical library, five compounds, curcumin (1), 3-(2
      naphthyloxy)-4-oxo-2-(trifluoromethyl)-4H-chromen-7-yl 3-chlorobenzoate (2),
      butyl 2-{[3-(2-naphthyloxy)-4-oxo-2-(trifluoromethyl)-4H-chromen-7
      yl]oxy}propanoate (3), 2-({2-[(2-{[2-(2,3-dimethylanilino)-2-oxoethyl]sulfanyl}
      1,3-benzothiazol-6-yl)amino]-2-oxoethyl}sulfanyl)-N-(2-naphthyl)acetamide (4),
      and maesaquinone diacetate (5) were discovered as HpSDH inhibitors with IC(50)
      values of 15.4, 3.9, 13.4, 2.9, and 3.5 microm, respectively. Further
      investigation indicates that compounds 1, 2, 3, and 5 demonstrate noncompetitive
      inhibition pattern, and compound 4 displays competitive inhibition pattern with
      respect to shikimate. Compounds 1, 4, and 5 display noncompetitive inhibition
      mode, and compounds 2 and 3 show competitive inhibition mode with respect to
      NADP. Antibacterial assays demonstrate that compounds 1, 2, and 5 can inhibit the
      growth of H. pylori with MIC of 16, 16, and 32 microg.mL(-1), respectively. This
      current work is expected to favor better understanding the features of SDH and
      provide useful information for the development of novel antibiotics to treat H.
      pylori-associated infection.

PMID- 16972984
TI  - Birth characteristics and the risk of childhood leukaemias and lymphomas in New
      Zealand: a case-control study.
AB  - BACKGROUND: Some studies have found that lower parity and higher or lower social
      class (depending on the study) are associated with increased risks of childhood
      acute lymphoblastic leukaemia (ALL). Such findings have led to suggestions that
      infection could play a role in the causation of this disease. An earlier New
      Zealand study found a protective effect of parental marriage on the risk of
      childhood ALL, and studies elsewhere have reported increased risks in relation to
      older parental ages. This study aimed to assess whether lower parity, lower
      social class, unmarried status and older parental ages increase the risk of
      childhood ALL (primarily). These variables were also assessed in relation to the
      risks of childhood acute non-lymphoblastic leukaemia, non-Hodgkin's lymphomas and
      Hodgkin's disease. METHODS: A case control study was conducted. The cases were
      585 children diagnosed with leukaemias or lymphomas throughout New Zealand over a
      12 year period. The 585 age and sex matched controls were selected at random from
      birth records. Birth records from cases (via cancer registration record linkage)
      and from controls provided accurate data on maternal parity, social class derived
      from paternal occupation, maternal marital status, ages of both parents, and
      urban status based on the address on the birth certificate. Analysis was by
      conditional logistic regression. RESULTS: There were no statistically significant
      associations overall between childhood ALL and parity of the mother, social
      class, unmarried maternal status, increasing parental ages (continuous analysis),
      or urban status. We also found no statistically significant associations between
      the risks of childhood acute non-lymphoblastic leukaemia, non-Hodgkin lymphomas,
      or Hodgkin's disease and the variables studied. CONCLUSION: This study showed no
      positive results though of reasonable size, and its record linkage design
      minimised bias. Descriptive studies (eg of time trends of ALL) show that
      environmental factors must be important for some diagnoses. Work has been done on
      the risk of ALL in relation to chemicals (eg pesticides) and drugs, dietary
      factors (eg vitamins), electromagnetic fields and infectious hypotheses (to name
      some); but whether these or other unknown factors are truly important remains to
      be seen.

PMID- 16972985
TI  - Use of pre-packaged chloroquine for the home management of presumed malaria in
      Malagasy children.
AB  - OBJECTIVE: The main objective of this study was to assess the quality of home
      malaria management with pre-packaged chloroquine in two areas in the Moramanga
      district of Madagascar. The knowledge, attitude and practices of care providers
      in terms of home treatment options were evaluated and compared. The availability
      of treatment options by studying retailers and community-based service providers
      was also investigated. METHODS: A cross-sectional investigation in two
      communities, in the hamlets and villages located close to carers, retailers,
      community-based service providers and primary health centres was carried out.
      RESULTS: Carers in the two districts were equally well aware of the use of pre
      packaged chloroquine. Their first response to the onset of fever was to treat
      children with this antimalarial drug at home. The dose administered and treatment
      compliance were entirely satisfactory (100%) with pre-packaged chloroquine and
      rarely satisfactory (1.6% to 4.5%) with non pre-packaged chloroquine. In cases of
      treatment failure, the carers took patients to health centres. Chloroquine was
      supplied principally by private pharmacies and travelling salesmen selling
      unpackaged chloroquine tablets. Non pre-packaged chloroquine was the most common
      drug used at health centres. The frequency of positive rapid malaria tests (P =
      0.01) was significantly higher in children treated with non pre-packaged
      chloroquine (38%) than in children treated with pre-packaged chloroquine (1.3%).
      CONCLUSION: Home malaria management should be improved in Madagascar. Efforts
      should focus on communication, the training of community-based service providers,
      access to pre-packaged drugs and the gradual withdrawal of pre-packaged
      chloroquine and its replacement by pre-packaged artemisinin-based combination
      therapies.

PMID- 16972986
TI  - Putative cross-kingdom horizontal gene transfer in sponge (Porifera)
      mitochondria.
AB  - BACKGROUND: The mitochondrial genome of Metazoa is usually a compact molecule
      without introns. Exceptions to this rule have been reported only in corals and
      sea anemones (Cnidaria), in which group I introns have been discovered in the
      cox1 and nad5 genes. Here we show several lines of evidence demonstrating that
      introns can also be found in the mitochondria of sponges (Porifera). RESULTS: A
      2,349 bp fragment of the mitochondrial cox1 gene was sequenced from the sponge
      Tetilla sp. (Spirophorida). This fragment suggests the presence of a 1143 bp
      intron. Similar to all the cnidarian mitochondrial introns, the putative intron
      has group I intron characteristics. The intron is present in the cox1 gene and
      encodes a putative homing endonuclease. In order to establish the distribution of
      this intron in sponges, the cox1 gene was sequenced from several representatives
      of the demosponge diversity. The intron was found only in the sponge order
      Spirophorida. A phylogenetic analysis of the COI protein sequence and of the
      intron open reading frame suggests that the intron may have been transmitted
      horizontally from a fungus donor. CONCLUSION: Little is known about sponge
      associated fungi, although in the last few years the latter have been frequently
      isolated from sponges. We suggest that the horizontal gene transfer of a
      mitochondrial intron was facilitated by a symbiotic relationship between fungus
      and sponge. Ecological relationships are known to have implications at the
      genomic level. Here, an ecological relationship between sponge and fungus is
      suggested based on the genomic analysis.

PMID- 16972987
TI  - Measuring health-related quality of life in young adolescents: reliability and
      validity in the Norwegian version of the Pediatric Quality of Life Inventory 4.0
      (PedsQL) generic core scales.
AB  - BACKGROUND: Health-Related Quality of Life (HRQOL) studies concerning children
      and adolescents are a growing field of research. The Pediatric Quality of Life
      Inventory (PedsQL) is considered as a promising HRQOL instrument with the
      availability of age appropriate versions and parallel forms for both child and
      parents. The purpose of the current study was to evaluate the psychometric
      properties of the Norwegian translation of the Pediatric Quality of Life
      Inventory (PedsQL) 4.0 generic core scale in a sample of healthy young
      adolescents. METHODS: A cross-sectional study of 425 healthy young adolescents
      and 237 of their caregivers participating as a proxy. Reliability was assessed by
      Cronbach's alpha. Construct validity was assessed using exploratory factor
      analysis and by exploring the intercorrelations between and among the four PedsQL
      subscales for adolescents and their parents. RESULTS: All the self-report scales
      and proxy-report scales showed satisfactory reliability with Cronbach's alpha
      varying between 0.77 and 0.88. Factor analysis showed results comparable with the
      original version, except for the Physical Health scale. On average, monotrait
      multimethod correlations were higher than multitrait-multimethod correlations.
      Sex differences were noted on the emotional functioning subscale, girls reported
      lower HRQOL than boys. CONCLUSION: The Norwegian PedsQL is a valid and reliable
      generic pediatric health-related Quality of Life measurement that can be
      recommended for self-reports and proxy-reports for children in the age groups
      ranging from 13-15 years.

PMID- 16972988
TI  - Transcriptional analysis of the recA gene of Streptococcus thermophilus.
AB  - BACKGROUND: RecA is a highly conserved prokaryotic protein that not only plays
      several important roles connected to DNA metabolism but also affects the cell
      response to various stress conditions. While RecA is highly conserved, the
      mechanism of transcriptional regulation of its structural gene is less conserved.
      In Escherichia coli the LexA protein acts as a recA repressor and is able, in
      response to DNA damage, of RecA-promoted self-cleavage, thus allowing recA
      transcription. The LexA paradigm, although confirmed in a wide number of cases,
      is not universally valid. In some cases LexA does not control recA transcription
      while in other RecA-containing bacteria a LexA homologue is not present. RESULTS:
      We have studied the recA transcriptional regulation in S. thermophilus, a
      bacterium that does not contain a LexA homologue. We have characterized the
      promoter region of the gene and observed that its expression is strongly induced
      by DNA damage. The analysis of deletion mutants and of translational gene fusions
      showed that a DNA region of 83 base pairs, containing the recA promoter and the
      transcriptional start site, is sufficient to ensure normal expression of the
      gene. Unlike LexA of E. coli, the factor controlling recA expression in S.
      thermophilus acts in a RecA-independent way since recA induction was observed in
      a strain carrying a recA null mutation. CONCLUSION: In S. thermophilus, as in
      many other bacteria,recA expression is strongly induced by DNA damage, however,
      in this organism expression of the gene is controlled by a factor different from
      those well characterized in other bacteria. A small DNA region extending from 62
      base pairs upstream of the recA transcriptional start site to 21 base pairs
      downstream of it carries all the information needed for normal regulation of the
      S. thermophilus recA gene.

PMID- 16972990
TI  - Standard setting: comparison of two methods.
AB  - BACKGROUND: The outcome of assessments is determined by the standard-setting
      method used. There is a wide range of standard-setting methods and the two used
      most extensively in undergraduate medical education in the UK are the norm
      reference and the criterion-reference methods. The aims of the study were to
      compare these two standard-setting methods for a multiple-choice question
      examination and to estimate the test-retest and inter-rater reliability of the
      modified Angoff method. METHODS: The norm-reference method of standard-setting
      (mean minus 1 SD) was applied to the 'raw' scores of 78 4th-year medical students
      on a multiple-choice examination (MCQ). Two panels of raters also set the
      standard using the modified Angoff method for the same multiple-choice question
      paper on two occasions (6 months apart). We compared the pass/fail rates derived
      from the norm reference and the Angoff methods and also assessed the test-retest
      and inter-rater reliability of the modified Angoff method. RESULTS: The pass rate
      with the norm-reference method was 85% (66/78) and that by the Angoff method was
      100% (78 out of 78). The percentage agreement between Angoff method and norm
      reference was 78% (95% CI 69% - 87%). The modified Angoff method had an inter
      rater reliability of 0.81-0.82 and a test-retest reliability of 0.59-0.74.
      CONCLUSION: There were significant differences in the outcomes of these two
      standard-setting methods, as shown by the difference in the proportion of
      candidates that passed and failed the assessment. The modified Angoff method was
      found to have good inter-rater reliability and moderate test-retest reliability.

PMID- 16972989
TI  - Butyrate induces profound changes in gene expression related to multiple signal
      pathways in bovine kidney epithelial cells.
AB  - BACKGROUND: Global gene expression profiles of bovine kidney epithelial cells
      regulated by sodium butyrate were investigated with high-density oligonucleotide
      microarrays. The bovine microarray with 86,191 distinct 60mer oligonucleotides,
      each with 4 replicates, was designed and produced with Maskless Array Synthesizer
      technology. These oligonucleotides represent approximately 45,383 unique cattle
      sequences. RESULTS: 450 genes significantly regulated by butyrate with a median
      False Discovery Rate (FDR) = 0 % were identified. The majority of these genes
      were repressed by butyrate and associated with cell cycle control. The expression
      levels of 30 selected genes identified by the microarray were confirmed using
      real-time PCR. The results from real-time PCR positively correlated (R = 0.867)
      with the results from the microarray. CONCLUSION: This study presented the genes
      related to multiple signal pathways such as cell cycle control and apoptosis. The
      profound changes in gene expression elucidate the molecular basis for the
      pleiotropic effects of butyrate on biological processes. These findings enable
      better recognition of the full range of beneficial roles butyrate may play during
      cattle energy metabolism, cell growth and proliferation, and possibly in fighting
      gastrointestinal pathogens.

PMID- 16972991
TI  - Patterns of clinical presentation of adult coeliac disease in a rural setting.
AB  - BACKGROUND: In recent years there has been increasing recognition that the
      pattern of presentation of coeliac disease may be changing. The classic sprue
      syndrome with diarrhoea and weight loss may be less common than the more subtle
      presentations of coeliac disease such as an isolated iron deficiency anaemia. As
      a result, the diagnosis of this treatable condition is often delayed or missed.
      Recent serologic screening tests allow non-invasive screening to identify most
      patients with the disease and can be applied in patients with even subtle
      symptoms indicative of coeliac disease. Both benign and malignant complications
      of coeliac disease can be avoided by early diagnosis and a strict compliance with
      a gluten free diet. AIM: The aim of this study is to evaluate the trends in
      clinical presentation of patients diagnosed with adult coeliac disease. In
      addition, we studied the biochemical and serological features and the prevalence
      of associated conditions in patients with adult coeliac disease. METHODS: This is
      an observational, retrospective, cross-sectional review of the medical notes of
      32 adult patients attending the specialist coeliac clinic in a district general
      hospital. RESULTS: Anaemia was the most common mode of presentation accounting
      for 66% of patients. Less than half of the patients had any of the classical
      symptoms of coeliac disease and 25% had none of the classical symptoms at
      presentation. Anti-gliadin antibodies, anti-endomysial antibody and anti-tissue
      transglutaminase showed 75%, 68% and 90% sensitivity respectively. In
      combination, serology results were 100% sensitive as screening tests for adult
      coeliac disease. Fifty nine percent patients had either osteoporosis or
      osteopenia. There were no malignant complications observed during the follow up
      of our patients. CONCLUSION: Most adults with coeliac disease have a sub clinical
      form of the disease and iron deficiency anaemia may be its sole presenting
      symptom. Only a minority of adult coeliac disease patients present with classical
      mal-absorption symptoms of diarrhoea and weight loss. Patients with atypical form
      of disease often present initially to hospital specialists other than a gastro
      enterologist. An awareness of the broad spectrum of presentations of adult
      coeliac disease, among doctors both in primary care and by the various hospital
      specialists in secondary care, is necessary to avoid delays in diagnosis. It is
      important to include serological screening tests for coeliac disease
      systematically in the evaluation of adult patients with unexplained iron
      deficiency anaemia or unexplained gastro-intestinal symptoms and in those who are
      considered to be at increased risk for coeliac disease.

PMID- 16972992
TI  - The Pro-children Project--a cross-national approach to increasing fruits and
      vegetables in the next generation and onwards.
AB  - This editorial introduces the special series in the International Journal of
      Behavioral Nutrition and Physical Activity on the Pro Children study (Promoting
      and Sustaining Health through Increased vegetable and Fruit Consumption among
      European Schoolchildren). The Pro Children study is a new and innovative study
      that takes a cross--national approach to identifying the factors associated with
      fruit and vegetables consumption in European children (from nine countries) and
      evaluating a multi-centre intervention programme. A full set of papers on many
      aspects of the study will appear as a series in the IJBPNA allowing a more
      detailed view of design, behavioural theoretical constructs, action, methods for
      implementation, assessment tools, impacts and outcomes to be reported. Areas for
      future work will also be identified and discussed in the context of the 21st
      century developed world environment which is superb at encouraging the promotion
      of energy dense foods and drinks.

PMID- 16972993
TI  - Effects of low-dose tamoxifen on breast cancer biomarkers Ki-67, estrogen and
      progesterone receptors.
AB  - Breast carcinoma is the most common malignancy among women and it has a major
      impact on mortality. Studies of primary chemoprevention with tamoxifen have
      generated high expectations and considerable success rates. The efficacy of lower
      doses of tamoxifen is similar to that seen with a standard dose of the drug, and
      there has been a reduction in healthcare costs and side effects. The immune
      reaction to monoclonal antibody Ki-67 (MIB-1) and the expression of estrogen
      receptors (1D5) and progesterone receptors (PgR 636) in breast carcinoma were
      studied in patients treated with 10 mg of tamoxifen for a period of 14 days. A
      prospective randomized clinical trial was conducted with 38 patients divided into
      two groups: Group A: N = 20 (control group--without medication) and Group B: N =
      18 (tamoxifen/10 mg/day for 14 days). All patients signed an informed consent
      term previously approved by both institutions. Patients underwent incisional
      biopsy before treatment and 14 days later a tumor tissue sample was obtained
      during surgical treatment. Positivity was quantitatively assessed, counting at
      least 1.000 cells per slide. For statistical data analysis, a Wilcoxon non
      parametric test was used, and alpha was set at 5%. Both groups (A and B) were
      considered homogeneous regarding control variables. In Group A (control), there
      was no statistically significant reduction in Ki-67 (MIB-1) (p = 0.627), estrogen
      receptor (1D5) (p = 0.296) and progesterone receptor positivity (PgR 636) (p =
      0.381). In Group B (tamoxifen 10 mg/day), the mean percentage of nuclei stained
      by Ki-67 (MIB-1) was 24.69% before and 10.43% after tamoxifen treatment. Mean
      percentage of nuclei stained by estrogen receptor (1D5) was 59.53% before and
      25.99% after tamoxifen treatment. Mean percentage of nuclei stained by
      progesterone receptor (PgR 636), was 59.34 before and 29.59% after tamoxifen
      treatment. A statistically significant reduction was found with the three markers
      (p < 0.001). Tamoxifen significantly reduced monoclonal antibody Ki-67 (MIB-1),
      estrogen receptor (1D5) and progesterone receptor positivity (PgR 636) in the
      breast epithelium of carcinoma patients treated with a 10 mg dose of tamoxifen
      for 14 days.

PMID- 16972994
TI  - Decreased metalloproteinase production as a response to mechanical pressure in
      human cartilage: a mechanism for homeostatic regulation.
AB  - Articular cartilage is optimised for bearing mechanical loads. Chondrocytes are
      the only cells present in mature cartilage and are responsible for the synthesis
      and integrity of the extracellular matrix. Appropriate joint loads stimulate
      chondrocytes to maintain healthy cartilage with a concrete protein composition
      according to loading demands. In contrast, inappropriate loads alter the
      composition of cartilage, leading to osteoarthritis (OA). Matrix
      metalloproteinases (MMPs) are involved in degradation of cartilage matrix
      components and have been implicated in OA, but their role in loading response is
      unclear. With this study, we aimed to elucidate the role of MMP-1 and MMP-3 in
      cartilage composition in response to mechanical load and to analyse the
      differences in aggrecan and type II collagen content in articular cartilage from
      maximum- and minimum-weight-bearing regions of human healthy and OA hips. In
      parallel, we analyse the apoptosis of chondrocytes in maximal and minimal load
      areas. Because human femoral heads are subjected to different loads at defined
      sites, both areas were obtained from the same hip and subsequently evaluated for
      differences in aggrecan, type II collagen, MMP-1, and MMP-3 content (enzyme
      linked immunosorbent assay) and gene expression (real-time polymerase chain
      reaction) and for chondrocyte apoptosis (flow cytometry, bcl-2 Western blot, and
      mitochondrial membrane potential analysis). The results showed that the load
      reduced the MMP-1 and MMP-3 synthesis (p < 0.05) in healthy but not in OA
      cartilage. No significant differences between pressure areas were found for
      aggrecan and type II collagen gene expression levels. However, a trend toward
      significance, in the aggrecan/collagen II ratio, was found for healthy hips (p =
      0.057) upon comparison of pressure areas (loaded areas > non-loaded areas).
      Moreover, compared with normal cartilage, OA cartilage showed a 10- to 20-fold
      lower ratio of aggrecan to type II collagen, suggesting that the balance between
      the major structural proteins is crucial to the integrity and function of the
      tissue. Alternatively, no differences in apoptosis levels between loading areas
      were found--evidence that mechanical load regulates cartilage matrix composition
      but does not affect chondrocyte viability. The results suggest that MMPs play a
      key role in regulating the balance of structural proteins of the articular
      cartilage matrix according to local mechanical demands.

PMID- 16972995
TI  - Brugada syndrome.
AB  - A novel clinical entity characterized by ST segment elevation in right precordial
      leads (V1 to V3), incomplete or complete right bundle branch block, and
      susceptibility to ventricular tachyarrhythmia and sudden cardiac death has been
      described by Brugada et al. in 1992. This disease is now frequently called
      "Brugada syndrome" (BrS). The prevalence of BrS in the general population is
      unknown. The suggested prevalence ranges from 5/1,000 (Caucasians) to 14/1,000
      (Japanese). Syncope, typically occurring at rest or during sleep (in individuals
      in their third or fourth decades of life) is a common presentation of BrS. In
      some cases, tachycardia does not terminate spontaneously and it may degenerate
      into ventricular fibrillation and lead to sudden death. Both sporadic and
      familial cases have been reported and pedigree analysis suggests an autosomal
      dominant pattern of inheritance. In approximately 20% of the cases BrS is caused
      by mutations in the SCN5A gene on chromosome 3p21-23, encoding the cardiac sodium
      channel, a protein involved in the control of myocardial excitability. Since the
      use of the implantable cardioverter defibrillator (ICD) is the only therapeutic
      option of proven efficacy for primary and secondary prophylaxis of cardiac
      arrest, the identification of high-risk subjects is one of the major goals in the
      clinical decision-making process. Quinidine may be regarded as an adjunctive
      therapy for patients at higher risk and may reduce the number of cases of ICD
      shock in patients with multiple recurrences.

PMID- 16972996
TI  - Renal cell carcinoma metastasizing to duodenum: a rare occurrence.
AB  - BACKGROUND: Duodenal metastasis is rare in renal cell carcinoma (RCC) and early
      detection, especially in case of a solitary mass, helps in planning further
      therapy. CASE PRESENTATION: We present the case report of a 55 year old male with
      duodenal metastasis of RCC. This patient presented with jaundice and abdominal
      lump one year after nephrectomy. On upper gastrointestinal endoscopy a submucosal
      mass lesion was noted in the duodenum, the biopsy of which revealed metastasis.
      CONCLUSION: In a nephrectomized patient presenting with jaundice and an abdominal
      mass, the possibility of metastasis should be suspected and a complete
      evaluation, especially endoscopic examination followed by biopsy, should be
      carried out.

PMID- 16972997
TI  - Molecular epidemiology of clinical and carrier strains of methicillin resistant
      Staphylococcus aureus (MRSA) in the hospital settings of north India.
AB  - BACKGROUND: The study was conducted between 2000 and 2003 on 750 human subjects,
      yielding 850 strains of staphylococci from clinical specimens (575), nasal
      cultures of hospitalized patients (100) and eye & nasal sources of hospital
      workers (50 & 125 respectively) in order to determine their epidemiology,
      acquisition and dissemination of resistance genes. METHODS: Organisms from
      clinical samples were isolated, cultured and identified as per the standard
      routine procedures. Susceptibility was measured by the agar diffusion method, as
      recommended by the National Committee for Clinical Laboratory Standards (NCCLS).
      The modified method of Birnboin and Takahashi was used for isolation of plasmids
      from staphylococci. Pulsed-field gel electrophoresis (PFGE) typing of clinical
      and carrier Methicillin resistant Staphylococcus aureus (MRSA) strains isolated
      during our study was performed as described previously. RESULTS: It was shown
      that 35.1% of Staphylococcus aureus and 22.5% of coagulase-negative
      staphylococcal isolates were resistant to methicillin. Highest percentage of MRSA
      (35.5%) was found in pus specimens (n = 151). The multiple drug resistance of all
      MRSA (n = 180) and Methicillin resistant Coagulase-negative Staphylococcus aureus
      (MRCNS) (n = 76) isolates was detected. In case of both methicillin-resistant as
      well as methicillin-sensitive Saphylococcal isolates zero resistance was found to
      vancomycin where as highest resistance was found to penicillin G followed by
      ampicillin. It was shown that the major reservoir of methicillin resistant
      staphylococci in hospitals are colonized/infected inpatients and colonized
      hospital workers, with carriers at risk for developing endogenous infection or
      transmitting infection to health care workers and patients. The results were
      confirmed by molecular typing using PFGE by SmaI-digestion. It was shown that the
      resistant markers G and T got transferred from clinical S. aureus (JS-105) to
      carrier S. aureus (JN-49) and the ciprofloxacin (Cf) and erythromycin (E)
      resistance seemed to be chromosomal mediated. In one of the experiments, plasmid
      pJMR1O from Staphylococcus aureus coding for ampicillin (A), gentamicin (G) and
      amikacin (Ak) resistance was transformed into Escherichia coli. The minimal
      inhibitory concentrations (MICs) for A and G were lower in E. coli than in S.
      aureus. However, the MIC for Ak was higher in E. coli transformants than in S.
      aureus. CONCLUSION: There is a progressive increase in MRSA prevalence and multi
      drug resistance in staphylococci. Vancomycin is still the drug of choice for MRSA
      infections. The major reservoir of methicillin resistant staphylococci in
      hospitals is colonized/infected inpatients and colonized hospital workers.
      Resistance transfer from staphylococci to E. coli as well as from clinical to
      carrier staphylococci due to antibiotic stress seemed to be an alarming threat to
      antimicrobial chemotherapy.

PMID- 16972998
TI  - Crisis and chaos in behavioral nutrition and physical activity.
AB  - Resnicow & Vaughn challenged the field of behavioral nutrition and physical
      activity to conduct research in new ways. They challenged the predictiveness of
      our models, sensitivity to initial conditions, factors predisposing to change and
      measurement procedures. While the predictiveness of our models will reflect the
      sophistication of our thinking and research, and the sensitivity to initial
      conditions is subsumed under the sophistication of our models, research on
      conditions predisposing to change (e.g. epiphanies), more longitudinal designs,
      refined measurement procedures and testing of critical issues can only enhance
      the quality of our research. Improved research quality should lead to enhanced
      efficacy and effectiveness of our interventions, and thereby our making
      meaningful contributions to mitigating the chaos in our field and the crisis from
      the rising epidemic of obesity.

PMID- 16972999
TI  - Girls' perception of physical environmental factors and transportation:
      reliability and association with physical activity and active transport to
      school.
AB  - BACKGROUND: Preliminary evidence suggests that the physical environment and
      transportation are associated with youth physical activity levels. Only a few
      studies have examined the association of physical environmental factors on
      walking and bicycling to school. Therefore, the purpose of this study was (1) to
      examine the test-retest reliability of a survey designed for youth to assess
      perceptions of physical environmental factors (e.g. safety, aesthetics,
      facilities near the home) and transportation, and (2) to describe the
      associations of these perceptions with both physical activity and active
      transport to school. METHODS: Test and retest surveys, administered a median of
      12 days later, were conducted with 480 sixth- and eighth-grade girls in or near
      six U.S. communities. The instrument consisted of 24 questions on safety and
      aesthetics of the perceived environment and transportation and related
      facilities. Additionally, girls were asked if they were aware of 14 different
      recreational facilities offering structured and unstructured activities, and if
      so, whether they would visit these facilities and the ease with which they could
      access them. Test-retest reliability was determined using kappa coefficients,
      overall and separately by grade. Associations with physical activity and active
      transport to school were examined using mixed model logistic regression (n =
      610), adjusting for grade, race/ethnicity, and site. RESULTS: Item-specific
      reliabilities for questions assessing perceived safety and aesthetics of the
      neighborhood ranged from 0.31 to 0.52. Reliabilities of items assessing awareness
      of and interest in going to the 14 recreational facilities ranged from 0.47 to
      0.64. Reliabilities of items assessing transportation ranged from 0.34 to 0.58.
      Some items on girls' perceptions of perceived safety, aesthetics of the
      environment, facilities, and transportation were important correlates of physical
      activity and, in some cases, active transport to school. CONCLUSION: This study
      provides some psychometric support for the use of the questionnaire on physical
      environmental factors and transportation for studying physical activity and
      active transport to school among adolescent girls. Further work can continue to
      improve reliability of these self-report items and examine their association of
      these factors with objectively measured physical activity.

PMID- 16973000
TI  - Interpreting the results of patient reported outcome measures in clinical trials:
      the clinician's perspective.
AB  - This article deals with the problem of interpreting health-related quality of
      life (HRQL) outcomes in clinical trials. First, we will briefly describe how
      dichotomization and item response theory can facilitate interpretation. Based on
      examples from the medical literature for the interpretation of HRQL scores we
      will show that dichotomies may help clinicians understand information provided by
      HRQL instruments in RCTs. They can choose thresholds to calculate proportions of
      patients benefiting based on absolute scores or change scores. For example,
      clinicians interpreting clinical trial results could consider the difference in
      the proportion of patients who achieve a mean score of 50 before and after an
      intervention on a scale from 1 to 100. For the change score approach, they could
      consider the proportion of patients who have changed by a score of 5 or more.
      Finally, they can calculate the proportion of patients benefiting and transform
      these numbers into a number needed to treat or natural frequencies. Second, we
      will describe in more detail an approach to the interpretation of HRQL scores
      based on the minimal important difference (MID) and proportions. The MID is the
      smallest difference in score in the outcome of interest that informed patients or
      informed proxies perceive as important, either beneficial or harmful, and that
      would lead the patient or clinician to consider a change in the management. Any
      change in management will depend on the downsides, including cost and
      inconvenience, associated with the intervention. Investigators can help with the
      interpretation of HRQL scores by determining the MID of an HRQL instrument and
      provide mean differences in relation to the MID. For instance, for an MID of 0.5
      on a seven point scale investigators could provide the mean change on the
      instrument as well as the proportion of patients with scores greater than the
      MID. Thus, there are several steps investigators can take to facilitate this
      process to help bringing HRQL information closer to the bedside.

PMID- 16973002
TI  - A bright future for Chlamydomonas.

PMID- 16973003
TI  - Myeloma (multiple).

PMID- 16973001
TI  - PhyloFacts: an online structural phylogenomic encyclopedia for protein functional
      and structural classification.
AB  - The Berkeley Phylogenomics Group presents PhyloFacts, a structural phylogenomic
      encyclopedia containing almost 10,000 'books' for protein families and domains,
      with pre-calculated structural, functional and evolutionary analyses. PhyloFacts
      enables biologists to avoid the systematic errors associated with function
      prediction by homology through the integration of a variety of experimental data
      and bioinformatics methods in an evolutionary framework. Users can submit
      sequences for classification to families and functional subfamilies. PhyloFacts
      is available as a worldwide web resource from
      http://phylogenomics.berkeley.edu/phylofacts.

PMID- 16973004
TI  - Non-Hodgkin's lymphoma (diffuse large B cell lymphoma).

PMID- 16973005
TI  - Sickle cell disease.

PMID- 16973006
TI  - Angina (stable).

PMID- 16973007
TI  - Heart failure.

PMID- 16973008
TI  - Myocardial infarction.

PMID- 16973009
TI  - Peripheral arterial disease.

PMID- 16973010
TI  - Secondary prevention of ischaemic cardiac events.

PMID- 16973011
TI  - Stroke management.

PMID- 16973012
TI  - Varicose veins.

PMID- 16973013
TI  - Ventricular tachyarrhythmias (out of hospital cardiac arrests).

PMID- 16973014
TI  - Attention deficit hyperactivity disorder in children.

PMID- 16973015
TI  - Depression in children and adolescents.

PMID- 16973016
TI  - Febrile seizures.

PMID- 16973017
TI  - Infantile colic.

PMID- 16973018
TI  - Measles, mumps, and rubella: prevention.

PMID- 16973019
TI  - Migraine headache in children.

PMID- 16973020
TI  - Neonatal infection: group B streptococcus.

PMID- 16973021
TI  - Nocturnal enuresis in children.

PMID- 16973022
TI  - Nosebleeds in children.

PMID- 16973023
TI  - Otitis media in children (acute).

PMID- 16973024
TI  - Perinatal asphyxia.

PMID- 16973025
TI  - Diabetic nephropathy.

PMID- 16973026
TI  - Dyslipidaemia in diabetes.

PMID- 16973027
TI  - Foot ulcers and amputations in diabetes.

PMID- 16973028
TI  - Glycaemic control in type 1 diabetes.

PMID- 16973029
TI  - Prevention of cardiovascular events in diabetes.

PMID- 16973030
TI  - Colorectal cancer.

PMID- 16973031
TI  - Colorectal cancer screening.

PMID- 16973032
TI  - Haemorrhoids.

PMID- 16973033
TI  - Stomach cancer.

PMID- 16973034
TI  - Chronic suppurative otitis media.

PMID- 16973035
TI  - Otitis media with effusion.

PMID- 16973036
TI  - Age related macular degeneration.

PMID- 16973037
TI  - Diabetic retinopathy.

PMID- 16973038
TI  - Ocular herpes simplex.

PMID- 16973039
TI  - HIV infection.

PMID- 16973040
TI  - Pneumocystis pneumonia in people with HIV.

PMID- 16973041
TI  - Amoebic dysentery.

PMID- 16973042
TI  - Diarrhoea in adults (acute).

PMID- 16973043
TI  - Hepatitis B (prevention).

PMID- 16973044
TI  - Hepatitis C (chronic).

PMID- 16973045
TI  - Leprosy.

PMID- 16973046
TI  - Malaria: severe, life threatening.

PMID- 16973047
TI  - End stage renal disease.

PMID- 16973048
TI  - Renal failure (acute).

PMID- 16973049
TI  - Benign prostatic hyperplasia.

PMID- 16973051
TI  - Chronic prostatitis.

PMID- 16973052
TI  - Varicocele.

PMID- 16973050
TI  - Erectile dysfunction.

PMID- 16973053
TI  - Bulimia nervosa.

PMID- 16973054
TI  - Depression in adults.

PMID- 16973055
TI  - Panic disorder.

PMID- 16973056
TI  - Ankle sprain.

PMID- 16973057
TI  - Bunions.

PMID- 16973058
TI  - Fracture prevention in postmenopausal women.

PMID- 16973059
TI  - Gout.

PMID- 16973060
TI  - Herniated lumbar disc.

PMID- 16973061
TI  - Leg cramps.

PMID- 16973062
TI  - Low back pain (acute).

PMID- 16973063
TI  - Low back pain (chronic).

PMID- 16973064
TI  - Neck pain.

PMID- 16973065
TI  - Bell's palsy.

PMID- 16973066
TI  - Trigeminal neuralgia.

PMID- 16973067
TI  - Candidiasis (oropharyngeal).

PMID- 16973068
TI  - Impacted wisdom teeth.

PMID- 16973069
TI  - Perineal care.

PMID- 16973070
TI  - Postnatal depression.

PMID- 16973071
TI  - Postpartum haemorrhage: prevention.

PMID- 16973072
TI  - Preterm birth.

PMID- 16973073
TI  - Recurrent miscarriage.

PMID- 16973074
TI  - Bronchitis (acute).

PMID- 16973075
TI  - Common cold.

PMID- 16973076
TI  - Community acquired pneumonia.

PMID- 16973077
TI  - Spontaneous pneumothorax.

PMID- 16973078
TI  - Bronchiectasis.

PMID- 16973079
TI  - Chronic obstructive pulmonary disease.

PMID- 16973080
TI  - Chlamydia (uncomplicated, genital).

PMID- 16973081
TI  - Genital warts.

PMID- 16973082
TI  - Gonorrhoea.

PMID- 16973083
TI  - Pelvic inflammatory disease.

PMID- 16973085
TI  - Cellulitis and erysipelas.

PMID- 16973084
TI  - Acne vulgaris.

PMID- 16973086
TI  - Fungal toenail infections.

PMID- 16973088
TI  - Scabies.

PMID- 16973087
TI  - Chronic plaque psoriasis.

PMID- 16973089
TI  - Breast cancer (metastatic).

PMID- 16973090
TI  - Breast cancer (non-metastatic).

PMID- 16973091
TI  - Dysmenorrhoea.

PMID- 16973092
TI  - Endometriosis.

PMID- 16973093
TI  - Female infertility.

PMID- 16973094
TI  - Recurrent cystitis in non-pregnant women.

PMID- 16973095
TI  - Pressure ulcers.

PMID- 16973096
TI  - Venous leg ulcers.

PMID- 16973098
TI  - An individualized psychosocial approach for "treatment resistant" behavioral
      symptoms of dementia among aged care residents.
AB  - BACKGROUND: Behavioral symptoms of dementia are common among residents in
      mainstream aged care settings, and have a substantial impact on residents and
      professional caregivers. This study evaluated the impact of individualized
      psychosocial interventions for behavioral symptoms through a small preliminary
      study. METHOD: Interventions were delivered to a patient group of 31
      psychogeriatric aged care residents who presented with behavioral symptoms of
      dementia that had failed to respond to pharmacological treatment approaches.
      Outcome data on severity of behaviors, health service utilization and staff
      burden of care were collected. RESULTS: A modest but significant reduction in
      staff ratings of the severity of aggressive and verbally agitated behavioral
      symptoms was found, with an associated reduction in their perceptions of the
      burden of caring for these patients. Reduced behavioral disturbance was
      associated with a reduction in the requirement for primary care consultations,
      and all participants were able to continue to reside in mainstream aged care
      facilities, despite an increase in the severity of dementia. CONCLUSIONS: This
      study supported the use of individualized psychological strategies for behavioral
      symptoms at all stages of dementia. Methodological limitations of this
      preliminary study are discussed.

PMID- 16973099
TI  - Severe domestic squalor: a review.
AB  - BACKGROUND: Referrals to clinical services of people living in severe domestic
      squalor are not uncommon. It is timely to review literature concerning and
      discussing such cases. METHOD: Using Medline, Psychinfo, Embase, CINAHL and
      reference lists from relevant publications, literature referring to over 1100
      cases was identified and then reviewed. RESULTS: Half of those described as
      living in severe squalor are elderly. Outcomes of intervention are often poor.
      People living in severe squalor are most commonly diagnosed as having dementia,
      alcoholism or schizophrenia, though personality problems are evident in a high
      proportion. There is evidence to suggest that neglect of hygiene and of attention
      to cleanliness of accommodation may be largely attributable to frontal lobe
      changes. The review also revealed a second body of literature, not often cited in
      papers focussed on unclean living conditions and published in psychiatric or
      medical journals, that concludes that hoarding is most commonly due to obsessive
      compulsive disorder (OCD). Accumulation of rubbish is described in over half of
      the case reports on severe domestic squalor, but it is suggested that this should
      only be called hoarding if it results from purposeful collection of items. Lack
      of impulse control may contribute to collecting behavior, resulting in reduction
      in living space if there is also a failure to discard. CONCLUSIONS: There is a
      need for further studies, using standardized ratings of living conditions,
      investigating and trying to understand the complex interplay of triggers and
      vulnerabilities, exploring how best to intervene and examining outcomes of
      interventions.

PMID- 16973100
TI  - Predictors of psychological adjustment after bereavement.
AB  - BACKGROUND: The impact of spousal bereavement on mental health varies among the
      widowed. More information is needed on factors influencing bereavement outcome.
      METHOD: We conducted a cross-sectional study on a sample of 216 widowed
      individuals. Initial non-response was high, with only 8% of all approached
      persons participating in the study. The influence of demographic and psychosocial
      predictors on four general outcome measures (depression, anxiety, somatization,
      and quality of life) and one loss-related outcome (complicated grief) was studied
      by means of backward linear regression analysis. Further analyses were performed
      to explore the possibility of a buffer effect. RESULTS: Depressive symptomatology
      was best predicted by: age, duration of widowhood, perceived non-supportiveness,
      physical disorders, and mastery. The other outcome measures were predicted by the
      same predictors supplemented by gender and education. Mastery interacted with the
      number of physical disorders while perceived social support interacted with
      duration of widowhood and age. CONCLUSIONS: Enhancement of mastery should
      probably be one of the components of effective support for widowed individuals
      most vulnerable to psychiatric complications. The widowed could furthermore
      benefit from social support. Obviously, these suggestions need to be further
      examined in longitudinal research with more representative samples.

PMID- 16973101
TI  - The incidence of delirium associated with orthopedic surgery: a meta-analytic
      review.
AB  - BACKGROUND: The aim of this study was to perform a systematic review and meta
      analysis of the literature regarding the incidence of delirium following
      orthopedic surgery. METHODS: Relevant papers were sourced from online databases
      and gray literature. Included studies used a validated diagnostic method to
      measure the incidence of delirium in a prospective sample of adult/elderly
      orthopedic patients. Data were subject to meta-analysis after stratification by
      type of surgery (elective v. emergency) and inclusion/exclusion of pre-existing
      cognitive impairment. A funnel plot assessed for publication bias. RESULTS: 26
      publications reported an incidence of postoperative delirium of 4-53.3% in hip
      fracture samples and 3.6-28.3% in elective samples. Significant heterogeneity was
      evident, and this persisted despite stratification. Hip fracture was associated
      with a higher risk of delirium than elective surgery both when the cognitively
      impaired were included in the sample (random effects pooled estimate = 21.7% [95%
      CI = 14.6-28.8] vs. 12.1% [95% CI = 9.6-14.6]), and when the cognitively impaired
      were excluded (random effects pooled estimate = 25% [95% CI = 15.7-34.7] vs. 8.8%
      [95% CI = 4.1-13.6]). The funnel plot showed a deficit of small studies showing
      low risk and large studies showing high risk. In eight hip fracture studies, the
      proportion of delirium cases with a preoperative onset ranged from 34 to 92%.
      CONCLUSIONS: Delirium occurs more commonly with hip fracture than elective
      surgery, and frequently has a preoperative onset when associated with trauma.
      Recommendations are made with the aim of standardizing future research in order
      to further explore and reduce the heterogeneity and possible publication bias
      observed.

PMID- 16973102
TI  - The impact of location on satisfaction with dementia services amongst people with
      dementia and their informal carers: a comparative evaluation of a community-based
      and a clinic-based memory service.
AB  - BACKGROUND: The development of effective medication for the treatment of
      Alzheimer's disease led to an expansion in the use of memory clinics ther clinic
      based services for the delivery and monitoring of the drugs. In contrast, there
      is an increased emphasis on providing home and community based service delivery
      for a range of illnesses including dementia. METHODS: This paper reports the
      findings of an evaluation study comparing a clinic-based and a community service.
      A convenience sample of 10 service users and carer dyads took part in in-depth
      qualitative interviews. Service users were diagnosed with mild to moderate
      dementia of Alzheimer's type. Interviews were recorded, transcribed and
      subsequently analyzed using template analysis. RESULTS: Service users and carers
      were satisfied with both services, with determinants of satisfaction differing
      between the two services. Issues relating to the location and spatial design of
      services, comfort, familiarity, communication with staff, and ease of use are
      highlighted as important determinants of satisfaction amongst service users and
      their carers. CONCLUSION: This study has implications for person-centred care
      practices in service delivery and for the future design of mental health services
      for people with dementia.

PMID- 16973103
TI  - Aging, muscles, and rheumatoid arthritis.

PMID- 16973105
TI  - Mechanisms of pathologic new bone formation.
AB  - Pathologic new bone formation occurs in response to a variety of stimuli.
      Heterotopic and orthotopic bone formation can interfere with the normal function
      of the joint and can contribute to disability in inflammatory joint diseases.
      Syndesmophyte formation and progressive ankylosis are characteristic features of
      spondyloarthropathies, including psoriatic arthritis and ankylosing spondylitis,
      and they can be regarded as abnormal bone remodeling. Successful blocking of
      inflammation in patients with spondyloarthropathy apparently fails to halt
      progression of ankylosis in cohort studies. This suggests that though they may be
      linked in some way, bone formation and inflammation are largely independent
      phenomena. Indeed, new bone formation also occurs in diseases such as
      osteoarthritis and diffuse idiopathic skeletal hyperostosis. Therefore,
      therapeutic strategies in spondyloarthropathy ideally should control both
      inflammation and bone formation.

PMID- 16973106
TI  - Dactylitis: pathogenesis and clinical considerations.
AB  - Dactylitis is considered a hallmark feature of psoriatic arthritis (PsA), but it
      is found in other spondyloarthropathies, especially reactive arthritis, and other
      conditions (eg, sarcoidosis, gout, sickle cell disease, and a variety of
      infections). Dactylitis is difficult to define and assess with any level of
      consensus and consistency in PsA. A new objective measure has been developed to
      make assessment more uniform for clinical trials. The underlying pathophysiology
      has also been difficult to determine in spondyloarthropathy: synovitis,
      tenosynovitis, and enthesitis have all been recognized. The pathophysiology in
      other conditions varies but usually involves soft tissue and sometimes involves
      bone or joint. In non-spondyloarthropathies,treatment is determined by the
      underlying cause. Research on dactylitis treatment in PsA suffers from a paucity
      of trials and inconsistent outcome measurement. The only drug with good evidence
      of benefit from randomized controlled trials thus far is infliximab.

PMID- 16973107
TI  - Animal models of psoriasis and psoriatic arthritis: an update.
AB  - Psoriasis is a chronic inflammatory skin disorder characterized by accelerated
      growth and altered differentiation of keratinocytes and angiogenesis with marked
      ectasia of blood vessels. It develops through interactions between the skin and
      immune system mediated by T cells, dendritic cells, and inflammatory cytokines.
      The understanding of the cellular and molecular alterations underlying the
      disease has advanced, yet the majority of factors leading to the initiation and
      maintenance of disease remain elusive. Researchers have attempted to reproduce
      psoriasis in genetically modified and xenotransplantation mouse models to gain
      insight into its pathogenesis, and they are beginning to use these models to test
      new therapeutic agents and define mechanisms of action. Every mouse model has
      strengths and weaknesses, with room for improvement. Still, these models will
      accelerate knowledge of psoriasis pathogenesis and aid in the development of new
      therapeutics.

PMID- 16973108
TI  - Management of psoriatic arthritis: the therapeutic interface between rheumatology
      and dermatology.
AB  - Psoriatic arthritis is an inflammatory arthritis, which occurs in up to 30% of
      individuals with psoriasis. Dermatologists and other physicians treating
      psoriasis are in an ideal position to screen for the condition, and with
      rheumatologists, strategize optimal therapy. Mild skin and joint manifestations
      may be treated effectively with topical agents, ultraviolet light therapy, and
      nonsteroidal anti-inflammatory drugs. More severe manifestations of the disease,
      including progressive peripheral joint damage, spine disease, enthesitis,
      dactylitis, and severe skin changes, require systemic therapy. Traditional
      systemic agents include methotrexate, sulfasalazine, and cyclosporine. When these
      agents are not adequate or not tolerated, new biologic agents, particularly anti
      tumor necrosis factor (TNF) compounds, have shown significant and enduring
      benefit in all disease domains, improvement in quality of life and function, and
      inhibition of progressive joint damage.

PMID- 16973109
TI  - Metabolic disorders in patients with psoriasis and psoriatic arthritis.
AB  - Psoriasis is one of the common complex disorders in Western world, affecting 2%
      to 3% of the population. Recent studies indicate that psoriasis is associated
      with an increased risk of comorbidity and mortality compared to the general
      population. It appears that patients with psoriasis have a higher prevalence of
      metabolic disorders such as diabetes, hypertension, obesity, and hyperlipidemia,
      as well as a higher frequency of cigarette smoking. These concomitant diseases
      can complicate the treatment of psoriasis. Even though the etiology of these
      associations is elusive, physicians should be aware of them and take active steps
      to reduce the risk profiles of patients with psoriasis and psoriatic arthritis,
      in order to lessen mortality and comorbidity.

PMID- 16973111
TI  - Genetic markers of treatment response in rheumatoid arthritis.
AB  - Rheumatoid arthritis patients exhibit a considerable interindividual variability
      in response to drug treatment. Although many disease-related and demographic
      factors have been studied to predict treatment outcome, the effective disease
      modifying antirheumatic drug (DMARD) therapy is not yet allocated based on
      factors that predict efficacy. Individual genetic characteristics are thought to
      play an important role in treatment response; therefore, current research aims to
      identify these genetic predictors for clinical response. Pharmacogenetic studies
      are beginning to provide results, which suggests that personalized treatment
      maximization of DMARD efficacy and minimization of adverse drug reactions are
      feasible.

PMID- 16973112
TI  - Ultrasonography and magnetic resonance imaging in early rheumatoid arthritis:
      recent advances.
AB  - Efficient methods for diagnosis, monitoring, and prognostication are essential in
      early rheumatoid arthritis. Data on the value of ultrasonography and MRI are
      accumulating rapidly, fueling their increasing use in early rheumatoid arthritis.
      This review focuses on recent advances in the clinical applications of these
      imaging modalities.

PMID- 16973113
TI  - Gene therapy works in animal models of rheumatoid arthritis...so what!
AB  - Rheumatoid arthritis (RA) is a systemic disease with polyarticular manifestation
      of chronic inflammation in the knees and small joints of hand and feet. The
      current systemic anti-tumor necrosis factor (TNF)-alpha therapies with biologics
      ameliorate disease in 60% to 70% of RA patients. However, biologics must be given
      systemically in relatively high dosages to achieve constant therapeutic levels in
      the joints, and side effects have been reported. To this end, local gene delivery
      can provide an alternative approach to achieve high, long-term expression of
      biologics, optimizing the therapeutic efficacy and minimizing systemic exposure.
      Evidence from animal models convincingly supports the application of local gene
      therapy in rheumatoid arthritis, but preclinical studies remain necessary to
      evaluate the merge of cell-specific targeting, viral vector development, and
      disease-regulated transgene expression to optimize efficacy and safety.

PMID- 16973114
TI  - Recent advances in the genetics of rheumatoid arthritis.
AB  - Recent progress in defining the role of genetic factors in rheumatoid arthritis
      (RA) has been remarkable. Anticyclic citrullinated peptide (anti-CCP) antibody
      positive disease appears to be immunogenetically distinct from anti-CCP-negative
      disease, with the former subgroup primarily responsible for association and
      linkage with the HLA-DRB1 shared epitope (SE). There is preliminary evidence that
      non-HLA genes contribute differentially to anti-CCP-positive and negative
      disease. The phenotypic differences evident in anti-CCP-positive and negative
      disease suggest a need to reclassify RA based on the presence or absence of this
      autoantibody. Some recent work also suggests marked interactions between
      cigarette smoking, anti-CCP antibodies, and the SE, though these relationships
      may vary across populations. Lastly, a recent single nucleotide polymorphism
      based genome-wide linkage analysis of multicase RA families revealed novel
      genomic regions that likely contain genes that predispose to RA or more specific
      phenotypes.

PMID- 16973116
TI  - Transmission of encephalomyocarditis virus in pigs estimated from field data in
      Belgium by means of R0.
AB  - Transmission of encephalomyocarditis-virus (EMCV) has been estimated in
      experiments, but never using field data. In this field study, a farm in Belgium
      was selected where the presence of EMCV was confirmed by necropsy and virus
      isolation. Serology was used to estimate the transmission parameter R0. In one
      compartment with 630 pigs, 6 pens were fully sampled, in the remaining 38 pens, 2
      randomly selected pigs were bled. The 151 pigs were bled twice and their serum
      was tested in a virus neutralisation test. Seroprevalence at the first and second
      sampling was 41 and 43% respectively, with a cut off value of 1:40. R0 was
      estimated for 2 scenarios, in- and excluding mortality based on the final sizes
      from the serological results of the second sampling. The R0 for the fully sampled
      pens was estimated between 0.6 and 1.7, the combined estimated R0 of these 6 pens
      was 1.36 (95%-CI 0.93-2.23). The median of the estimated R0 of the partially
      sampled pens was 1.3 and 1.4. Sampling two pigs per pen provided insight into the
      spread of the virus in the compartment, while the fully sampled pens provided an
      accurate estimation of R0. The low R0 strongly suggests that EMCV is not very
      effectively transmitted between pigs. The number of seropositive pigs in a pen
      and the spread in the compartment suggests that other routes of infection are
      more important, in this case most likely rodents. Preventing viral spread should
      therefore be focussed on rodent control instead of reduction of contact between
      pigs.

PMID- 16973115
TI  - Exacerbation of Chlamydophila psittaci pathogenicity in turkeys superinfected by
      Escherichia coli.
AB  - Both Chlamydophila psittaci and Escherichia coli infections are highly prevalent
      in Belgian turkeys and therefore they both might contribute to the respiratory
      disease complex observed in turkeys. C. psittaci can infect turkeys within the
      first week of age, even in the presence of maternal antibodies. However, the
      first C. psittaci outbreaks occur mostly at the age of 3 to 6 weeks, the period
      when also E. coli infections appear on the farms. Therefore, we examined in this
      study the pathogenicity of an E. coli superinfection on C. psittaci predisposed
      turkeys. Turkeys were infected with C. psittaci, E. coli or with C. psittaci
      followed by E. coli. Simulating the impact of an E. coli infection during the
      acute phase or the latent phase of a C. psittaci infection, turkeys received E.
      coli at 1 or 5 weeks post C. psittaci infection, respectively. E. coli
      superinfection during the acute phase of C. psittaci infection increased C.
      psittaci excretion and stimulated chlamydial replication in the respiratory tract
      resulting in exacerbated clinical disease. Interestingly, E. coli superinfection
      during the latent phase of C. psittaci infection induced chlamydial replication,
      leading to increased C. psittaci-specific antibody titres. In addition,
      chlamydial predisposition gave higher E. coli excretion compared with turkeys
      that had only been infected with E. coli. Overall, the present study clearly
      demonstrates the pathogenic interplay between C. psittaci and E. coli resulting
      in more severe respiratory disease.

PMID- 16973117
TI  - Extensive rearing hinders Maedi-Visna Virus (MVV) infection in sheep.
AB  - Maedi-Visna Virus (MVV) seroprevalence and its relationship with housing and mode
      of rearing of replacement ewe-lambs was investigated in 38 non-randomly selected
      sheep-flocks in Spain. They included extensive lamb-producing Manchega cross-bred
      flocks raised almost permanently at pasture, semi-intensive Latxa dairy flocks
      housed 2-8 months/year and intensively raised Assaf dairy flocks housed most time
      and at higher stocking density in less ventilated buildings than other flocks.
      Most flocks raised replacement lambs naturally with their dams until weaning and
      as a separate flock thereafter until lambing at one year of age. Seroprevalence
      (95% confidence intervals) was 77%, 25% and 5% (4-6) in intensive, semi-intensive
      and extensive flocks, respectively and the median (interquartile range) flock
      seroprevalence was 82% (66-94) in intensive flocks, 31% (14-31) in semi-intensive
      flocks and 4% (0-7) in extensive flocks. Seroprevalence was lowest in one year
      old sheep and increased to flock levels during the year after introduction into
      the adult flock in most intensive flocks and more gradually in other flocks.
      Adult flock seroprevalence was associated with housing time but this relationship
      was not evident within a particular rearing system, indicating that other unknown
      factors are critical in horizontal MVV-transmission. Low seroprevalence in
      extensive flocks further supports previous indications that lactogenic MVV
      infection is relatively inefficient and horizontal transmission is necessary to
      ensure long-term maintenance of MVV and this could explain that MVV has not been
      reported from countries with mainly extensively reared sheep such as Australia
      and New Zealand. Moreover, it indicates that MVV-control in extensive and semi
      intensive flocks can be simple and inexpensive.

PMID- 16973118
TI  - Mycoplasma mycoides subsp. capri and Mycoplasma mycoides subsp. mycoides LC can
      be grouped into a single subspecies.
AB  - Mycoplasma mycoides subsp. capri and Mycoplasma mycoides subsp. mycoides LC can
      be combined into one taxon on the basis of several contributions on both DNA
      sequence and protein analyses reported in the literature. Moreover, for the
      differentiation and identification of mycoplasmas of the "mycoides cluster", we
      investigated the rpoB gene, encoding the beta-subunit of the RNA polymerase. A
      segment of 527 bp of the rpoB gene was amplified from 31 strains of ruminant
      mycoplasmas by PCR. The nucleotide sequences were determined and aligned, and
      accurate genetic relationships were calculated. Cluster analysis of rpoB DNA
      allowed species differentiation within the "mycoides cluster" and confirmed that
      M. mycoides subsp. capri and M. mycoides subsp. mycoides LC cannot be
      distinguished from each other. "Mycoplasma mycoides subsp. capri" is proposed as
      a common name for both subspecies.

PMID- 16973119
TI  - Toll-like receptor 2 and 9 are expressed and functional in gut-associated
      lymphoid tissues of presuckling newborn swine.
AB  - To clarify the crucial role of Toll-like receptor (TLR) 2 and TLR9 in immature
      gut-associated lymphoid tissues (GALT), we focused on the expression of TLR2 and
      TLR9 and the immune responses induced by their ligands in the GALT of presuckling
      newborn swine. Quantitative real-time PCR revealed that TLR2 and TLR9 mRNA were
      expressed at detectable levels in all tested tissues (heart, thymus, lung,
      spleen, liver, kidney, skeletal muscle, duodenum, jejunum, ileum, ileal Peyer
      patches (Pps), and mesenteric lymph nodes (MLN)). In particular, in immature
      intestinal tissues and GALT, TLR2 and TLR9 mRNA were expressed at higher levels
      in ileal Pps and MLN than in the duodenum, jejunum, and ileum. We confirmed that
      the TLR2 and TLR9 proteins were also highly expressed and that their ligands were
      preferentially recognized by TLR2- or TLR9-expressing cells in the MLN and ileal
      Pps. Zymosan, CpG2006, and lactic acid bacteria could promote mitogenesis and
      production of multiple cytokines by the MLN and ileal Pps. In addition, double
      immunostaining for cytokeratin 18 and either TLR2 or TLR9 revealed that both TLR2
      and TLR9 are strongly expressed in the columnar membranous (M) cells.
      Interestingly, while the apical membrane of the columnar M cells strongly
      expressed TLR2 protein and preferentially recognized zymosan, both "TLR2
      expression on the apical membrane" and "TLR2-mediated zymosan binding" were
      negligible in neighboring enterocytes. These results indicate that TLR2 and TLR9
      allow MLN and ileal Pps to respond to a variety of bacterial components
      immediately after birth, thereby providing newborns with a host defense system.

PMID- 16973120
TI  - IgE and IgG antibodies in skin allergy of the horse.
AB  - In horses, allergies have been characterized by clinical signs and/or intradermal
      (i.d.) allergen testing. Our aim was to find the first direct evidence that
      immunoglobulin E (IgE) mediates equine allergy. In addition, we tested the
      hypothesis that immediate skin reactions in horses can also be mediated by IgG.
      Anti-IgE affinity columns were used to purify IgE from serum of one healthy horse
      and three horses affected with summer eczema, an allergic dermatitis which is
      believed to be induced by Culicoides midges. A modified Prausnitz-Kustner
      experiment was performed in four clinical healthy horses by i.d. injection of the
      purified serum IgE antibodies. The following day, Culicoides allergen was
      injected at the same sites. Skin reactions were not observed in response to
      allergen alone, and in two horses after stimulation at any previous IgE injection
      site. However, the other two horses showed an immediate skin reaction at the
      previous injection sites of IgE obtained from allergic horses. In addition,
      purified monoclonal antibodies to various equine immunoglobulin isotypes were
      injected i.d. into six healthy horses. Immediate skin reactions were observed in
      response to anti-IgE (6/6 horses) and anti-IgG(T) injections (5/6 horses). The
      specificities of both antibodies for IgE and IgG(T), respectively, were confirmed
      by enzyme linked immunosorbent assays. The results provide the first direct
      evidence that IgE mediates classical Type-I allergy in horses and plays a major
      role in the pathogenesis of summer eczema. The data also suggest that IgG(T) can
      bind to skin mast cells and might contribute to clinical allergy.

PMID- 16973121
TI  - Shedding routes of Coxiella burnetii in dairy cows: implications for detection
      and control.
AB  - Reliable detection of Coxiella burnetii shedders is a critical point for the
      control of the spread of this bacterium among animals and from animals to humans.
      Coxiella burnetii is shed by ruminants mainly by birth products (placenta, birth
      fluids), but may also be shed by vaginal mucus, milk, and faeces, urine and
      semen. However, the informative value of these types of samples to identify
      shedders under field conditions is unknown. Our aim was then to describe the
      responses obtained using a real-time PCR technique applied to milk, vaginal mucus
      and faeces samples taken from 242 dairy cows in commercial dairy herds known to
      be naturally infected with Coxiella burnetii, and to assess their putative
      associations. Positive results were found in all types of tested samples even in
      faeces. No predominant shedding route was identified. Among the shedder cows,
      65.4% were detected as shedders by only one route. By contrast, cows with
      positive results for all three samples were scarce (less than 7%). Testing a cow
      based on only one type of biological sample may lead to misclassify it with
      regards to its shedding of Coxiella burnetii and thereby underestimate the risk
      of bacterial spread within a herd.

PMID- 16973122
TI  - Modulation of FoxO signaling in human hepatoma cells by exposure to copper or
      zinc ions.
AB  - Cells respond to heavy metal stress by activating signaling cascades regulating
      cellular proliferation and survival. We here demonstrate that the anti-apoptotic
      kinase Akt is activated in HepG2 human hepatoma cells exposed to copper or zinc
      ions. Cu2+- and Zn2+-induced phosphorylation of Akt was blocked by
      phosphoinositide 3-kinase (PI3K) inhibitors, wortmannin and LY294002. Moreover,
      several endogenous Akt substrates were phosphorylated, including glycogen
      synthase kinase-3 and transcription factors of the FoxO family, FoxO1a and FoxO4.
      Exposure to Cu2+ or Zn2+ elicited the subcellular redistribution of an
      overexpressed FoxO1a-EGFP fusion protein from nucleus to cytoplasm, which was not
      seen with a mutant FoxO1a form devoid of Akt phosphorylation sites. Both FoxO
      phosphorylation and nuclear exclusion were blocked by wortmannin. Likewise, the
      subcellular translocation from nucleus to cytoplasm of the Caenorhabditis elegans
      FoxO ortholog, DAF-16, was caused in starved worms exposed to copper ions.
      Activity of the promoter of the human glucose 6-phosphatase gene, known to be
      regulated by insulin and FoxO1a, was demonstrated in reporter gene assays to be
      attenuated in hepatoma cells exposed to Cu2+. However, this suppression of
      glucose 6-phosphatase promoter activity was independent of modulation of the
      PI3K/Akt pathway. In summary, the PI3K/Akt pathway is activated in human hepatoma
      cells exposed to Cu2+ or Zn2+, resulting in the phosphorylation and subcellular
      relocalisation of transcription factor FoxO1a. Furthermore, copper is
      demonstrated to exert an insulin-mimetic effect also independently of the
      PI3K/Akt/FoxO pathway.

PMID- 16973123
TI  - Evidence for the transglycosylation of complex type oligosaccharides of
      glycoproteins by endo-beta-N-acetylglucosaminidase HS.
AB  - Transglycosylation activity of endo-beta-N-acetylglucosaminidase HS (Endo HS) was
      investigated using native human transferrin as a donor of an asparagine-linked
      oligosaccharide and p-nitrophenyl-beta-d-glucose (PNP-beta-d-Glc) as an acceptor
      of the oligosaccharide. The amount of the product increased dependent on the
      concentration of the acceptors. Absorption spectrum, exoglycosidase digestion and
      matrix assisted laser desorption and ionization-time of flight (MALDI-TOF) mass
      analysis of the transglycosylation product indicated that the asialobiantennary
      complex type oligosaccharide of human transferrin was transferred to PNP-beta-d
      Glc. Endo HS also transferred the oligosaccharide of human transferrin to PNP
      alpha-d-Glc, PNP-alpha-d-Gal, PNP-beta-d-Gal, PNP-beta-d-Man, PNP-beta-d-Xyl, PNP
      beta-d-GlcNAc, and PNP-glycerol at a different rate. No apparent difference in
      the K(m) value for human transferrin as an oligosaccharide donor was observed
      using different acceptors, PNP-beta-d-Glc and PNP-glycerol. The amount of the
      transglycosylation product successively increased and became constant and then
      very slightly decreased during the course of enzyme reaction. Endo HS was also
      transferred the triantennary complex type oligosaccharide of calf fetuin and the
      bi-, tri-, and tetrantennary complex type oligosaccharides of human alpha(1)-acid
      glycoprotein to PNP-beta-d-Glc. Furthermore, Endo HS transferred an asparagine
      linked oligosaccharide from a hen egg glycopeptide to PNP-beta-d-Glc. The results
      demonstrate that Endo HS can transfer a wide variety of asparagine-linked complex
      type oligosaccharides to various monosaccharides. Endo HS was distinct from other
      enzymes in the specificity for oligosaccharide donors and acceptors.

PMID- 16973124
TI  - Pig liver phosphomevalonate kinase: kinetic mechanism.
AB  - Phosphomevalonate kinase catalyzes the phosphorylation of phosphomevalonate to
      diphosphomevalonate by ATP, one of the initial steps in the biosynthesis of
      steroids and isoprenoids. In previous studies, the enzyme from pig liver was
      purified and characterized, and preliminary work showed that the enzyme follows
      hyperbolic kinetics and a sequential mechanism. The present work is a more
      detailed analysis of its kinetic mechanism, using initial velocity and isotope
      exchange at equilibrium measurements. The results are compatible with a Bi Bi
      sequential ordered mechanism with phosphomevalonate as the first substrate and
      ADP the last product. The Km values estimated are 43+/-7 microM for Mg-ATP and
      12+/-3 microM for phosphomevalonate, with a Vmax of 51+/-2 micromol min-1 mg of
      protein-1.

PMID- 16973125
TI  - Dissociation and serenity induction.
AB  - Dissociation is a common experience during or immediately after a traumatic
      event; yet, most of the current knowledge regarding dissociation is retrospective
      in nature. The aim of the present study investigated a non-pharmacological method
      of dissociative induction with a clinical sample. Participants with PTSD and non
      trauma exposed participants were randomly assigned to receive either a
      dissociative induction, or a serenity induction, based on modified Velten mood
      induction procedures. Participants receiving the dissociative induction reported
      higher state-dissociation than those receiving the serenity induction. The PTSD
      group reported greater state dissociation than the non-trauma exposed group,
      regardless of induction. State dissociation was related to trait dissociation,
      PTSD severity, and depression. The present results provide an initial
      demonstration of the viability for inducing state dissociation in the laboratory
      with a PTSD sample.

PMID- 16973126
TI  - Identification of human alpha-synuclein specific single chain antibodies.
AB  - Parkinson's disease (PD) is a common neurodegenerative disease of unknown
      etiology. Evidence suggests a role for protein misfolding in disease
      pathogenesis. One pathologic feature observed in dopaminergic neurons is the
      intracytoplasmic eosinophilic inclusions known as Lewy bodies. One component of
      Lewy bodies, the presynaptic protein, alpha-synuclein forms oligomers and higher
      order aggregates and is proposed to be involved in dopaminergic neuronal death.
      In an effort to discriminate between alpha-synuclein conformational forms as well
      as design potential disruptors of pathogenic misfolding we panned a human phage
      antibody library for anti-synuclein single chain antibodies (scFvs). We
      identified six scFvs which recognize different conformers of alpha-synuclein in
      both an ELISA and Western blot analysis. These scFvs may further our
      understanding of alpha-synuclein's role in PD.

PMID- 16973127
TI  - Structure of human protein kinase C eta (PKCeta) C2 domain and identification of
      phosphorylation sites.
AB  - Protein kinase C eta (PKCeta) is one of several PKC isoforms found in humans. It
      is a novel PKC isoform in that it is activated by diacylglycerol and anionic
      phospholipids but not calcium. The crystal structure of the PKCeta-C2 domain,
      which is thought to mediate anionic phospholipid sensing in the protein, was
      determined at 1.75 A resolution. The structure is similar to that of the PKC
      epsilon C2 domain but with significant variations at the putative lipid-binding
      site. Two serine residues within PKC eta were identified in vitro as potential
      autophosphorylation sites. In the unphosphorylated structure both serines line
      the putative lipid-binding site and may therefore play a role in the lipid
      regulation of the kinase.

PMID- 16973128
TI  - Exploring candidate genes for human brain diseases from a brain-specific gene
      network.
AB  - It is believed that large numbers of genes are involved in common human brain
      diseases. Here, we propose a novel computational strategy for simultaneously
      identifying multiple candidate genes for genetic human brain diseases from a
      brain-specific gene network-level perspective. By integrating diverse genomic and
      proteomic datasets based on Bayesian statistical model, we built a large-scale
      human brain-specific gene network. Based on this network and minor prior
      knowledge of a specific brain disease, we can effectively identify multiple
      candidate genes for this disease. When four known Alzheimer's disease genes were
      used as the prior knowledge, among the top 46 high-scoring genes that we have
      found, 37 were previously reported to be associated with Alzheimer's disease. And
      the higher score a gene has, the more likely this gene is a disease-related one.
      The results suggest that the proposed method is effective, convenient, and
      applicable in the future genetic studies.

PMID- 16973129
TI  - Glucocorticoid upregulation of the annexin-A1 receptor in leukocytes.
AB  - We tested here whether glucocorticoids modulated myeloid cell expression of a
      specific G-coupled receptor, termed formyl-peptide receptor like-1 (FPRL-1),
      recently shown to mediate the anti-inflammatory actions of annexin-A1. Real-time
      PCR and flow cytometry demonstrated rapid up-regulation of mRNA followed by the
      protein in HL-60 cells incubated with dexamethasone, with peaks at 2 and 24h,
      respectively. This effect was not restricted to dexamethasone, since reproduced
      by glucocorticoids. In addition, it was not restricted to the cell line, since
      replicated with human peripheral blood monocytes. Glucocorticoid ability to
      upregulate cell surface expression of FPRL-1 was specific, since no effects upon
      the related receptor FPR or the integrin CD11b could be detected. In view of the
      wide range of endogenous ligands known to interact with FPRL-1, including the
      anti-inflammatory protein annexin-A1, we speculate that the novel effect here
      described may impact on the clinical immunosuppressive and anti-inflammatory
      properties of glucocorticoids.

PMID- 16973130
TI  - A severe de novo methylation of episomal vectors by human ES cells.
AB  - Episomal vectors can allow efficient genetic modification of cells and have the
      potential advantage of avoiding chromosomal position of integration effects. Here
      we explore the use of an Epstein-Barr virus-based episomal vector with human
      embryonic stem (ES) cells, and find high initial transfection rates, but a rapid
      loss of reporter gene expression. Similar to mouse ES cells, human ES cells
      express high levels of the de novo DNA methyltransferases, and we detected
      dramatic CpG methylation and minor non-CpG methylation on the episomes recovered
      from the human ES cells 7 days after the transfection, which was not present on
      the same episome recovered from 293 cells. Interestingly, the oriP region of the
      episomes was relatively excluded from this methylation. These findings define
      some of the limitations of using episomal vectors with human ES cells and offer a
      unique platform for analyzing epigenetic gene silencing in human ES cells.

PMID- 16973131
TI  - Combinations of TLR and NOD2 ligands stimulate rat microglial P2X4R expression.
AB  - As ATP-gated ion channels, P2X4 receptors (P2X4R) of microglial cells play a
      crucial role in central nervous system (CNS) inflammation. In this study, we used
      rat microglial cell cultures to examine P2X4R expression in response to
      stimulation by combination of toll-like receptors (TLRs) and nucleotide-binding
      oligomerization domain 2 (NOD2) receptors. Various TLR1-9 ligands and NOD2
      agonist muramyldipeptide (MDP) were investigated. Our results showed that certain
      combination of ligands had additive effects on upregulating microglial P2X4R at
      both mRNA and protein levels, and induced nitric oxide increase and tumor
      necrosis factor-alpha production. Thus TLRs and NOD2 combinations are
      contributors to the signaling cascades resulting in purinergic microglial
      activation.

PMID- 16973132
TI  - Comparative proteomic analysis of mouse embryonic stem cells and neonatal-derived
      cardiomyocytes.
AB  - Pluripotent embryonic stem cells (ESCs) spontaneously differentiate via embryo
      like aggregates into cardiomyocytes. A thorough understanding of the molecular
      conditions in ESCs is necessary before other potential applications of these
      cells such as cell therapy can be materialized. We applied two dimensional
      electrophoresis to analyze and compare the proteome profiling of spontaneous
      mouse ESC-derived cardiomyocytes (ESC-DCs), undifferentiated mouse ESCs, and
      neonatal-derived cardiomyocytes (N-DCs). Ninety-five percent of the proteins
      detected on the ESC-DCs and N-DCs could be precisely paired with one other,
      whereas only twenty percent of the ESC proteins could be reliably matched with
      those on the ESC-DCs and N-DCSs, suggesting a striking similarity between them.
      Having identified sixty proteins in the said three cell types, we sought to
      provide possible explanations for their differential expression patterns and
      discuss their relevance to cell biology. This study provides a new insight into
      the gene expression pattern of differentiated cardiomyocytes and is further
      evidence for a close relation between ESC-DCs and N-DCSs.

PMID- 16973133
TI  - Can NF-kappaB be a target for novel and efficient anti-cancer agents?
AB  - Since the discovery of the NF-kappaB transcription factor in 1986 and the cloning
      of the genes coding for NF-kappaB and IkappaB proteins, many studies demonstrated
      that this transcription factor can, in most cases, protect transformed cells from
      apoptosis and therefore participate in the onset or progression of many human
      cancers. Molecular studies demonstrated that ancient widely used drugs, known for
      their chemopreventive or therapeutic activities against human cancers, inhibit NF
      kappaB, usually among other biological effects. It is therefore considered that
      the anti-cancer activities of NSAIDs (non-steroidal anti-inflammatory drugs) or
      glucocorticoids are probably partially related to the inhibition of NF-kappaB and
      new clinical trials are being initiated with old compounds such as sulfasalazine.
      In parallel, many companies have developed novel agents acting on the NF-kappaB
      pathway: some of these agents are supposed to be NF-kappaB specific (i.e. IKK
      inhibitors) while others have wide-range biological activities (i.e. proteasome
      inhibitors). Today, the most significant clinical data have been obtained with
      bortezomib, a proteasome inhibitor, for the treatment of multiple myeloma. This
      review discusses the preclinical and clinical data obtained with these various
      drugs and their putative future developments.

PMID- 16973134
TI  - Basis for dosing time-dependent change in the anti-tumor effect of imatinib in
      mice.
AB  - Because a variety of receptor tyrosine kinases are involved in the mechanism of
      tumor progression, the development of a clinically useful tyrosine kinase
      inhibitor is expected as a therapeutic agent for the treatment of malignant
      cancers. Imatinib mesylate, known as Gleevec or STI-571, is a molecule that
      inhibits the function of various receptors with tyrosine kinase activity, such as
      Abl, the bcr-abl chimeric product, KIT, and platelet-derived growth factor (PDGF)
      receptors. In this study, we investigated the influence of dosing time on the
      ability of imatinib to inhibit tumor growth in mice. Tumor-bearing mice were
      housed under standardized light/dark cycle conditions (lights on at 07:00 h, off
      at 19:00 h) with food and water ad libitum. The growth of tumor cells implanted
      in mice was more severely inhibited by the administration of imatinib (50 mg/kg,
      i.p.) in the early light phase than when it was administered in the early dark
      phase. The dosing time-dependency of anti-tumor effects was parallel to that of
      imatinib-induced anti-angiogenic effect. The inhibitory effect of imatinib on
      tyrosine kinase activity of PDGF receptors, but not of KIT and Abl, varied
      according to its administration time. The dosing time-dependency of imatinib
      induced inhibition of PDGF receptor activity was closely related to that of its
      anti-tumor effects. Our results suggest that the anti-tumor efficacy of imatinib
      is enhanced by administering the drug when PDGF receptor activity was increased.
      The potent therapeutic efficacy of the drug could be expected by optimizing the
      dosing schedule.

PMID- 16973135
TI  - Intracellular substrates of brain-enriched receptor protein tyrosine phosphatase
      rho (RPTPrho/PTPRT).
AB  - Receptor protein tyrosine phosphatase rho (RPTPrho/PTPRT) is a transmembrane
      protein that is highly expressed in the developing and adult central nervous
      system. It is a member of the RPTP R2B subfamily, which includes PTPkappa, PTPmu
      and PCP-2. Glutathione-S-transferase (GST) pulldown assays were used to show that
      RPTPrho interacts with several adherens junctional proteins in brain, including E
      cadherin, N-cadherin, VE-cadherin (cadherin-5), desmoglein, alpha, beta and gamma
      catenin, p120(ctn) and alpha-actinin. With the exception of E-cadherin and alpha
      actinin, binding was considerably reduced at high sodium concentrations.
      Furthermore, immunoprecipitation phosphatase assays indicated that E-cadherin,
      and to a far lesser extent p120(ctn), were tyrosine dephosphorylated by a
      recombinant RPTPrho intracellular fragment, and thus, were likely to be primary
      substrates for RPTPrho. The interaction of RPTPrho with adherens junctional
      components suggests that this phosphatase may transduce extracellular signals to
      the actin cytoskeleton and thereby play a role in regulating cadherin-mediated
      cell adhesion in the central nervous system.

PMID- 16973136
TI  - Esterification of select polyols with D-glucaric acid as model reactions for
      esterification of starch.
AB  - Aqueous solutions of D-glucaric acid and model polyols xylitol, methyl alpha-D
      glucopyranoside or beta-cyclodextrin were freeze dried, then heated, and the
      product mixtures analyzed by instrumental methods that included GC-MS,
      electrospray ionization-mass spectrometry (ESIMS), and NMR. The thermal process
      and analyses were carried out with these polyols in order to determine to what
      extent multiple acylations of the alcohol functions occurred with D-glucaric acid
      lactones serving as acylating agents, the extent to which acylations occurred at
      the 1 degrees alcohol sites, and the relative tendency for acylations to occur at
      the C1 or C6 end of the glucaryl unit. The results of these studies showed an
      overwhelming preference for 1 degrees alcohol acylation and preferred acylation
      occurring at the C1 end of the glucaryl unit.

PMID- 16973137
TI  - Direct C-glycosylation of indole with unprotected mono-, di-, and trisaccharides:
      a one-pot synthesis of 1-deoxy-1,1-bis(3-indolyl)alditols.
AB  - 1-Deoxy-1,1-bis(3-indolyl)alditols were synthesized by reacting 2.5equiv of
      indole with 1equiv of the following seven monosaccharides (D-galactose, D
      mannose, D-allose, 2-deoxy-D-arabinohexose (2-deoxy-D-glucose), D-arabinose, L
      arabinose, D-xylose), two disaccharides (D-lactose, D-maltose), and a
      trisaccharide (D-maltotriose) in 1:1 EtOH-H(2)O at room temperature, or at 40 or
      50 degrees C, in the presence of 5 mol% scandium(III) trifluoromethanesulfonate
      [Sc(OTf)(3)], in a one-pot reaction, in 36-95% yields.

PMID- 16973138
TI  - Dextran and 5-aminosalicylic acid (5-ASA) conjugates: synthesis, characterisation
      and enzymic hydrolysis.
AB  - Mesalamine (5-aminosalicylic acid) is the drug of choice for the treatment of
      Crohn's disease. A scheme for the synthesis of 5-aminosalicylic acid (5-ASA)
      conjugates of dextrans was developed with a focus on Crohn's disease
      applications. Dextrans were oxidised using sodium periodate (NaIO(4)), where the
      aldehyde groups formed were coupled with the alpha-amino (-NH(2)) group of 5-ASA.
      The resulting imine bonds were unstable in water and were consequently reduced to
      secondary amine groups. The effects of different aspects of the conjugation
      reaction were studied. These included the following: the molecular weight of the
      dextrans, the molar proportion of NaIO(4) to the dextrans (for periodate
      oxidation), the pH of the conjugation solutions, the ratio 5-ASA to oxidised
      polysaccharide and the relationship between the degree of conjugation and the
      amount of enzyme hydrolysis. Conjugates incubated in HCl were stable in 0.5 and
      1.0M HCl, but they underwent degradation in 2.0 and 4.0M HCl. Dextrans (MW
      20,000) with various degrees of oxidation (12%, 26%, 46%, 65%, 90% and 93%) were
      also prepared. Each oxidised dextran sample was conjugated with 5-ASA, and the
      product was quantified by high-performance liquid chromatography (HPLC). Dextrans
      with a maximum degree of oxidation (93%) unsurprisingly gave maximum conjugation
      of 5-ASA (49.1mg per 100mg of product) but were resistant to dextranase
      hydrolysis. Less oxidised dextrans (12%) conjugated proportionally less 5-ASA
      (15.1mg per 100mg of product) but were successfully hydrolysed by dextranase,
      suggesting their potential applications for the treatment of Crohn's disease in
      the distal ileum and proximal colon.

PMID- 16973139
TI  - Stereoselective synthesis of jaspine B from D-xylose.
AB  - The natural cytotoxic marine compound, jaspine B, is stereoselectively
      synthesized from D-xylose in 11 linear steps with a 23.9% overall yield. The key
      step in the synthesis involves an iodine-induced debenzylation of a primary
      alcohol and the subsequent 2,5-cyclization to fit the required configuration of
      jaspine B. A preliminary bioassay shows strong inhibition activities against
      human MDA231, Hela, and CNE cell lines, indicating potential usage in various
      cancer treatments.

PMID- 16973140
TI  - Synthesis of 2-deoxy-2-fluoro analogs of polyprenyl beta-D-arabinofuranosyl
      phosphates.
AB  - Described is the synthesis of polyprenyl 2-deoxy-2-fluoro-beta-D-arabinofuranosyl
      phosphate derivatives, including an analog of decaprenyl beta-D-arabinofuranosyl
      phosphate, the donor species used by the arabinosyltransferases involved in
      mycobacterial cell-wall biosynthesis. The targets were synthesized via a route
      involving the synthesis of a protected beta-D-arabinofuranosyl phosphate
      derivative, its coupling with a polyprenyl trichloroacetimidate, and then
      deprotection of the resulting product. The use of arabinofuranosyl phosphates
      with the monosaccharide hydroxyl groups protected as either silyl ethers or
      benzoate esters was explored. Although the coupling yields between the phosphate
      and polyprenyl trichloroacetimidates were comparable with either type of
      protecting group, access to the benzoyl-protected derivative was more efficient
      and therefore gave the products in higher overall yield.

PMID- 16973141
TI  - Quantitation of protein kinase A-mediated trafficking of cardiac sodium channels
      in living cells.
AB  - OBJECTIVE: Na(+) current derived from expression of the principal cardiac Na(+)
      channel, Na(v)1.5, is increased by activation of protein kinase A (PKA). This
      effect is blocked by inhibitors of cell membrane recycling, or removal of a
      cytoplasmic endoplasmic reticulum (ER) retention motif, suggesting that PKA
      stimulation increases trafficking of cardiac Na(+) channels to the plasma
      membrane. METHODS: To test this hypothesis, green fluorescent protein (GFP) was
      fused to Na(v)1.5 (Na(v)1.5-GFP), and the effects of PKA activation were
      investigated in intact, living cells that stably expressed the fusion protein.
      Using confocal microscopy, the spatial relationship of GFP-tagged channels
      relative to the plasma membrane was quantitated using a measurement that could
      control for variables present during live-cell imaging, and permit an unbiased
      analysis for all cells in a given field. RESULTS: In the absence of kinase
      stimulation, intracellular fluorescence representing Na(v)1.5-GFP channels was
      greatest in the perinuclear area, with additional concentration of channels
      beneath the cell surface. Activation of PKA promoted trafficking of Na(+)
      channels from both regions to the plasma membrane. Experimental results using a
      chemiluminescence-based assay further confirmed that PKA stimulation increased
      expression of Na(v)1.5 channels at the cell membrane. CONCLUSIONS: Our results
      provide direct evidence for PKA-mediated trafficking of cardiac Na(+) channels
      into the plasma membrane in living, mammalian cells, and they support the
      existence of multiple intracellular storage pools of channel protein that can be
      mobilized following a physiologic stimulus.

PMID- 16973142
TI  - Plasma granulysin concentrations and preeclampsia risk.
AB  - OBJECTIVE: Epidemiological, clinical and histological data suggest intriguing
      similarities between preeclampsia and graft-host-rejection. Granulysin, a novel
      biomarker of overall cellular immunity, is secreted by natural killer cells and
      cytotoxic T lymphocytes, which are associated with graft-host-rejection. Plasma
      granulysin was elevated in Japanese preeclamptic women. DESIGN AND METHODS: 50
      preeclampsia cases and 50 normotensive controls (USA) were studied. Plasma
      granulysin at delivery was determined using enzyme immunoassay. Logistic
      regression procedures were used to estimate odds ratios (OR) and 95% confidence
      intervals (CI). RESULTS: Granulysin were elevated in preeclampsia cases compared
      with controls (3.01+/-0.18 vs. 2.22+/-0.14 ng/mL, p<0.01). After adjusting for
      age, body-mass-index and race, women with higher granulysin concentrations (> or
      =1.89 ng/mL) experienced a 2.9-fold (95%CI 1.1-7.8) increased preeclampsia risk
      compared with women with lower granulysin (<1.89 ng/mL). CONCLUSIONS: These data
      offer further evidence of a predominant Th1 immune status associated with
      preeclampsia. Prospective studies are needed to determine whether granulysin is
      elevated early in pregnancy.

PMID- 16973143
TI  - Persistent structural priming from language comprehension to language production.
AB  - To examine the relationship between syntactic processes in language comprehension
      and language production, we compared structural persistence from sentence primes
      that speakers heard to persistence from primes that speakers produced. [Bock, J.
      K., & Griffin, Z. M. (2000). The persistence of structural priming: transient
      activation or implicit learning? Journal of Experimental Psychology: General,
      129, 177-192.] showed that the production of target priming structures increased
      the probability of spontaneously using the same structures to describe events in
      subsequent pictures that were semantically unrelated to the primes. These priming
      effects persisted across as many as ten intervening filler trials. The present
      studies replicated these results using auditorily presented primes to which
      participants only listened. The results indicated persistence of priming across
      all lags, with relative magnitudes of priming as large as those observed by Bock
      and Griffin. The implication is that structural priming is persistent regardless
      of the modality in which language structures are experienced, underscoring the
      power of priming as an implicit learning mechanism.

PMID- 16973144
TI  - Priming ditransitive structures in comprehension.
AB  - Many studies have shown evidence for syntactic priming during language production
      (e.g., Bock, 1986). It is often assumed that comprehension and production share
      similar mechanisms and that priming also occurs during comprehension (e.g.,
      Pickering & Garrod, 2004). Research investigating priming during comprehension
      (e.g., Branigan, Pickering, & McLean, 2005; Scheepers & Crocker, 2004) has mainly
      focused on syntactic ambiguities that are very different from the meaning
      equivalent structures used in production research. In two experiments, we
      investigated whether priming during comprehension occurs in ditransitive
      sentences similar to those used in production research. When the verb was
      repeated between prime and target, we observed a priming effect similar to that
      in production. However, we observed no evidence for priming when the verbs were
      different. Thus, priming during comprehension occurs for very similar structures
      as priming during production, but in contrast to production, the priming effect
      is completely lexically dependent.

PMID- 16973145
TI  - Adoptive immunotherapy of breast cancer with lymph node cells primed by
      cryoablation of the primary tumor.
AB  - Cryoablation of cancer leaves tumor-associated antigens intact in an inflammatory
      microenvironment that can stimulate a regional anti-tumor immune response. We
      examined whether cryoablated tumor draining lymph nodes (CTDLN) as adoptive
      immunotherapy may be an effective immunotherapeutic approach in the adjuvant
      treatment of breast cancer. BALB/c mice with MT-901 mammary adenocarcinoma tumors
      underwent cryoablation, resection or no treatment and tumor draining lymph nodes
      were harvested. Cryoablation resulted in only a mild increase in the absolute
      number of T-cells but a significant increase in the fraction of tumor-specific T
      cells as evidenced on IFN-gamma release assay. FACS analysis demonstrated no
      significant relative shift in the proportion of CD4(+) or CD8(+) cells. The
      adoptive transfer of CTDLN resulted in a significant reduction of pulmonary
      metastases as compared to TDLN from either tumor-bearing mice or mice who
      underwent surgical excision. Cryoablation prior to surgical resection of breast
      cancer can be used as a method to generate effector T-cells for adjuvant adoptive
      cellular immunotherapy.

PMID- 16973146
TI  - Stress-induced activation of the AMP-activated protein kinase in the freeze
      tolerant frog Rana sylvatica.
AB  - Survival in the frozen state depends on biochemical adaptations that deal with
      multiple stresses on cells including long-term ischaemia and tissue dehydration.
      We investigated whether the AMP-activated protein kinase (AMPK) could play a
      regulatory role in the metabolic re-sculpting that occurs during freezing. AMPK
      activity and the phosphorylation state of translation factors were measured in
      liver and skeletal muscle of wood frogs (Rana sylvatica) subjected to anoxia,
      dehydration, freezing, and thawing after freezing. AMPK activity was increased 2
      fold in livers of frozen frogs compared with the controls whereas in skeletal
      muscle, AMPK activity increased 2.5-, 4.5- and 3-fold in dehydrated, frozen and
      frozen/thawed animals, respectively. Immunoblotting with phospho-specific
      antibodies revealed an increase in the phosphorylation state of eukaryotic
      elongation factor-2 at the inactivating Thr56 site in livers from frozen frogs
      and in skeletal muscles of anoxic frogs. No change in phosphorylation state of
      eukaryotic initiation factor-2alpha at the inactivating Ser51 site was seen in
      the tissues under any of the stress conditions. Surprisingly, ribosomal protein
      S6 phosphorylation was increased 2-fold in livers from frozen frogs and 10-fold
      in skeletal muscle from frozen/thawed animals. However, no change in translation
      capacity was detected in cell-free translation assays with skeletal muscle
      extracts under any of the experimental conditions. The changes in phosphorylation
      state of translation factors are discussed in relation to the control of protein
      synthesis and stress-induced AMPK activation.

PMID- 16973147
TI  - Mutations in laminin alpha 1 result in complex, lens-independent ocular
      phenotypes in zebrafish.
AB  - We report phenotypic and genetic analyses of a recessive, larval lethal zebrafish
      mutant, bal(a69), characterized by severe eye defects and shortened body axis.
      The bal(a69) mutation was mapped to chromosome 24 near the laminin alpha 1
      (lama1) gene. We analyzed the lama1 gene sequence within bal(a69) embryos and two
      allelic mutants, bal(arl) and bal(uw1). Missense (bal(a69)), nonsense (bal(arl)),
      and frameshift (bal(uw1)) alterations in lama1 were found to underlie the
      phenotypes. Extended analysis of bal(a69) ocular features revealed disrupted lens
      development with subsequent lens degeneration, focal cornea dysplasia, and
      hyaloid vasculature defects. Within the neural retina, the ganglion cells showed
      axonal projection defects and ectopic photoreceptor cells were noted at inner
      retinal locations. To address whether ocular anomalies were secondary to defects
      in lens differentiation, bal(a69) mutants were compared to embryos in which the
      lens vesicle was surgically removed. Our analysis suggests that many of the
      anterior and posterior ocular defects in bal(a69) are independent of the lens
      degeneration. Analysis of components of focal adhesion signaling complexes
      suggests that reduced focal adhesion kinase activation underlies the anterior
      segment dysgenesis in lama1 mutants. To assess adult ocular phenotypes associated
      with lama1 mutations, genetic mosaics were generated by transplanting labeled bal
      cells into ocular-fated regions of wild-type blastulas. Adult chimeric eyes
      displayed a range of defects including anterior segment dysgenesis and cataracts.
      Our analysis provides mechanistic insights into the developmental defects and
      ocular pathogenesis caused by mutations in laminin subunits.

PMID- 16973148
TI  - The role of activin in neuropeptide induction and pain sensation.
AB  - Signals from target tissues play critical roles in the functional differentiation
      of neuronal cells, and in their subsequent adaptations to peripheral changes in
      the adult. Sensory neurons in the dorsal root ganglia (DRG) provide an excellent
      model system for the study of signals that regulate the development of neuronal
      diversity. DRG have been well characterized and contain both neurons that convey
      information from muscles about limb position, as well as other neurons that
      provide sensations from skin about pain information. Sensory neurons involved in
      pain sensation can be distinguished physiologically and antigenically, and one
      hallmark characteristic is that these neurons contain neuropeptides important for
      their functions. The transforming growth factor (TGF) beta family member activin
      A has recently been implicated in neural development and response to injury.
      During sensory neuron development, peripheral target tissues containing activin
      or activin itself can regulate pain neuropeptide expression. Long after
      development has ceased, skin target tissues retain the capacity to signal neurons
      about changes or injury, to functionally refine synapses. This review focuses on
      the role of activin as a target-derived differentiative factor in neural
      development that has additional roles in response to cutaneous injuries in the
      adult.

PMID- 16973149
TI  - Continuity versus split and reconstitution: exploring the molecular developmental
      corollaries of insect eye primordium evolution.
AB  - Holometabolous insects like Drosophila proceed through two phases of visual
      system development. The embryonic phase generates simple eyes of the larva. The
      postembryonic phase produces the adult specific compound eyes during late larval
      development and pupation. In primitive insects, by contrast, eye development
      persists seemingly continuously from embryogenesis through the end of
      postembryogenesis. Comparative literature suggests that the evolutionary
      transition from continuous to biphasic eye development occurred via transient
      developmental arrest. This review investigates how the developmental arrest model
      relates to the gene networks regulating larval and adult eye development in
      Drosophila, and embryonic compound eye development in primitive insects.
      Consistent with the developmental arrest model, the available data suggest that
      the determination of the anlage of the rudimentary Drosophila larval eye is
      homologous to the embryonic specification of the juvenile compound eye in
      directly developing insects while the Drosophila compound eye primordium is
      evolutionarily related to the yet little studied stem cell based postembryonic
      eye primordium of primitive insects.

PMID- 16973151
TI  - Pax6 is required for delta-catenin/neurojugin expression during retinal,
      cerebellar and cortical development in mice.
AB  - The transcription factor Pax6 regulates multiple aspects of central nervous
      system (CNS) development. At the cellular level, the Pax6 mutation was reported
      to affect homophilic and heterophilic cellular adhesion, neuron polarity and
      neurite outgrowth. These abnormalities were observed in multiple regions of Pax6
      mutant CNS, suggesting a common function for Pax6 in regulating cytoskeletal
      dynamics. However, target genes mediating Pax6 function in cytoskeletal dynamics
      remain largely unknown. Using DNA microarrays, we identified delta-catenin (delta
      catenin /neurojugin) as a potential direct target of Pax6 in the CNS. delta
      catenin encodes a large cytoskeletal protein that localizes at adherens junction
      in the CNS and that can modulate neurite outgrowth and N-cadherin turnover. delta
      catenin was found to be co-expressed with Pax6 in several regions of the
      developing CNS. In Pax6 mutant embryos, delta-catenin expression was severely
      reduced in the optic vesicle neural ectoderm, in the ventricular zone of the
      neocortex and in the external granule layer of the cerebellum. We identified a
      Pax6 binding site in delta-catenin promoter that is conserved between mice and
      humans and which is effectively bound by Pax6 in vitro. Our results suggest that
      Pax6 regulates delta-catenin expression during CNS development in mice.

PMID- 16973150
TI  - Smurf1 regulates neural patterning and folding in Xenopus embryos by antagonizing
      the BMP/Smad1 pathway.
AB  - The ubiquitin ligase Smurf1 can target a handful of signaling proteins for
      ubiquitin-mediated proteasomal destruction or functional modification, including
      TGF-beta receptors, Smads, transcription factors, RhoA and MEKK2. Smurf1 was
      initially implicated in BMP pathway regulation in embryonic development, but its
      potential role in vertebrate embryogenesis has yet to be clarified. Here we
      demonstrate that inhibition of Smurf1 in Xenopus laevis embryos with an antisense
      morpholino oligonucleotide or a dominant-negative protein disrupts early
      development, with the nervous system being the principal target. Smurf1 is
      enriched on the dorsal side of gastrula stage embryos, and blocking Smurf1
      disturbs neural folding and neural, but not mesoderm differentiation, enhances
      BMP/Smad1 signaling, and elevates phospho-Smad1 levels in the dorsal ectoderm. We
      conclude that in Xenopus embryos, the BMP pathway is a major physiological target
      of Smurf1, and we propose that in normal development Smurf1 cooperates with
      secreted BMP antagonists to limit BMP signaling in dorsal ectoderm. Our data also
      reveal a novel role for Smurf1 and Smad1 in neural plate morphogenesis.

PMID- 16973152
TI  - E3024, 3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5
      d]pyridazin-4-one tosylate, is a novel, selective and competitive dipeptidyl
      peptidase-IV inhibitor.
AB  - Dipeptidyl peptidase IV (DPP-IV) inhibitors are expected to become a useful new
      class of anti-diabetic agent. The aim of the present study is to characterize the
      in vitro and in vivo profile of E3024, 3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5
      dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate, which is a novel
      imidazopyridazinone-derived DPP-IV inhibitor. E3024 inhibited recombinant human
      and mouse DPP-IV with IC50 values of approximately 100 nM. E3024 inhibited DPP-IV
      in human, mouse, rat and canine plasma with IC50 values of 140 to 400 nM. In
      contrast, E3024 did not inhibit DPP-8 or DPP-9 activity. Kinetic analysis
      indicated that E3024 is a competitive DPP-IV inhibitor. In Zucker fa/fa rats,
      E3024 (1 mg/kg) reduced glucose excursion after glucose load, with increases in
      plasma insulin and active glucagon-like peptide-1 levels. In fasted rats, this
      compound did not cause hypoglycemia. In a rat 4-week toxicological study, no
      notable changes were found at doses up to 750 mg/kg. The present preclinical
      studies indicate that E3024 is a novel selective DPP-IV inhibitor with anti
      diabetic effects and a good safety profile.

PMID- 16973153
TI  - Pranlukast, a cysteinyl leukotriene receptor 1 antagonist, protects mice against
      brain cold injury.
AB  - We have reported the neuroprotective effect of cysteinyl leukotriene receptor 1
      (CysLT1) antagonists on cerebral ischemia. Here, we further determined the
      protective effect of pranlukast, a CysLT1 receptor antagonist, on brain cold
      injury in mice. Brains were injured by placing a cooled metal probe on the skull
      surface for 30 s. We found that pranlukast significantly reduced cold-induced
      lesion volume (0.3 mg/kg) and the percentage increase in lesioned hemisphere
      volume (0.03-0.3 mg/kg) 24 h after injury, but did not show any effect 72 h after
      injury. Pranlukast also significantly inhibited neuron loss 24 h (0.1 mg/kg) and
      72 h (0.1-0.3 mg/kg) after injury, and decreased the density of degenerated
      neurons 24 h (0.01-0.3 mg/kg) and 72 h (0.03-0.3 mg/kg) after injury. In
      addition, pranlukast (0.1-0.3 mg/kg) significantly reduced endogenous IgG
      exudation both 24 h and 72 h after injury. Thus, this study indicates the
      protective effect of pranlukast on brain cold injury.

PMID- 16973154
TI  - Simvastatin inhibits the migration and adhesion of monocytic cells and
      disorganizes the cytoskeleton of activated endothelial cells.
AB  - Statins are powerful agents for lowering plasma cholesterol levels, which act by
      inhibition of the 3-hydroxy-3-methylglutaryl-CoA reductase. Evidence suggests
      that some of the beneficial effects may depend on their anti-inflammatory
      properties, due to their ability to suppress the synthesis of isoprenoids. The
      present study analyzes the effects of short-term simvastatin exposure on monocyte
      migration, cell adhesion, and endothelial cytoskeleton. We demonstrate that
      simvastatin completely inhibited the migration of THP-1 monocytic cells after 24
      h of incubation, being prevented by coincubation with mevalonate (MVA) and
      geranylgeranylpyrophosphate (GGPP), but not by farnesylpyrophosphate (FPP).
      Simvastatin decreased chemotaxis to 70% after one hour of incubation;
      surprisingly neither MVA, GGPP nor FPP were able to restore the effects of the
      drug. Simvastatin also significantly reduced the adhesion of monocytes to
      interleukin-1beta (IL-1beta)-activated endothelium to 80% after preincubation for
      24 h. This effect was completely reversed by coincubation with MVA and GGPP, and
      partially with FPP. Unexpectedly, simvastatin increased adhesion molecules
      expression VCAM-1 and ICAM-1 on cytokine-stimulated endothelial cells.
      Examination of the actin cytoskeleton on IL-1beta-activated endothelial cells
      showed that both 4 and 24 h of incubation with simvastatin produced a complete
      disappearance of F-actin, being completely restored by MVA and partially by GGPP
      and FPP after 24 h of coincubation. We suggest that cytoskeleton disorganization
      in endothelial cells is important for inhibiting monocyte adhesion, altering the
      adhesion molecules function. Taken together, these results strongly support the
      beneficial anti-inflammatory properties of statins, contributing to the overall
      clinical effects.

PMID- 16973155
TI  - TEMPOL, a membrane-permeable radical scavenger, attenuates peroxynitrite- and
      superoxide anion-enhanced carrageenan-induced paw edema and hyperalgesia: a key
      role for superoxide anion.
AB  - Carrageenan produces both inflammation and pain when injected in rat paws via
      enhancement of the formation of reactive oxygen species. We have tested the
      effect of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL), a membrane
      permeable superoxide dismutase (SOD) mimetic in carrageenan-induced rat paw
      edema. Treatment of rats with TEMPOL (15, 30, and 60 mg/kg, 15 min prior to
      carrageenan) inhibited the paw edema. Furthermore, treatment of rats with the SOD
      inhibitor diethylthiocarbamate (DETCA, 100 mg/kg, 1 h before carrageenan)
      enhanced the carrageenan-induced paw edema. Co-administration of peroxynitrite
      with carrageenan produced a similar fortification of the carrageenan-induced
      edema. Prior treatment of rats with TEMPOL (30 mg/kg) inhibited the enhancement
      produced by DETCA treatment (endogenous superoxide anion stress) as well as that
      produced by the peroxynitrite stress. The effect of TEMPOL as well as the
      influence of superoxide anion and peroxynitrite stresses was also tested in
      carrageenan-induced hyperalgesia model. Carrageenan (500 mug/paw) produced
      significant hyperalgesia presented as shortening of withdrawal latency times
      using hot plate (52 degrees C) starting 30 min after carrageenan and lasting for
      3 h. TEMPOL (60 mg/kg, injected 15 min before carrageenan) ameliorated this
      hyperalgesia during the first 2 h. Concurrent administration of peroxynitrite
      promptly intensified the carrageenan hyperalgesia. TEMPOL (60 mg/kg, 15 min
      before peroxynitrite-carrageenan) inhibited the peroxynitrite enhancement of
      carrageenan hyperalgesia when tested at 60 min after injection of the cocktail.
      The present investigation gives the proof for the effectiveness of TEMPOL as anti
      inflammation and analgesic agents in carrageenan-induced model of inflammation
      and hyperalgesia. It further indicated the importance of superoxide anion and
      peroxynitrite in acute inflammation and inflammatory pain. This raises the
      chances for considering pharmacologic interventions that interrupt superoxide
      anion and peroxynitrite stress for putative alternative agents as anti
      inflammatory analgesic new medical strategies.

PMID- 16973156
TI  - Ginsenoside-Rd from panax notoginseng blocks Ca2+ influx through receptor- and
      store-operated Ca2+ channels in vascular smooth muscle cells.
AB  - Previously, it was found that total saponins from panax notoginseng inhibited
      Ca2+ influx coupling to activation of alpha1-adrenoceptor. This study was
      designed to investigate the effects of ginsenoside-Rd from total saponins of
      panax notoginseng on receptor-operated (ROCC) and store-operated (SOCC) Ca2+
      channels in vascular smooth muscle cells using fura-2 fluorescence, whole cell
      patch clamp ion channel recording, radio-ligand-receptor binding, 45Ca2+ radio
      trace and organ bath techniques. It was found that ginsenoside-Rd reduced
      phenylephrine-induced contractile responses and Ca2+ influx in normal media
      without significant effect on these responses in Ca2+ -free media. Ginsenoside-Rd
      also decreased phenylephrine- and thapsigargin-induced inward Ca2+ currents, and
      attenuated thapsigargin- and 1-oleoy-2-acetyl-sn-glycerol (OAG)-induced cation
      entries that are coupled to ROCC and SOCC respectively. Ginsenoside-Rd failed to
      inhibit KCl-induced contraction of rat aortal rings and Ca2+ influx, and did not
      alter voltage-dependent inward Ca2+ current (VDCC) which was blocked by
      nifedipine. Also, ginsenoside-Rd did not change binding site and affinity of [3H]
      prazosin for alpha1-adrenoceptor in the vascular plasma membrane. These results
      suggest that ginsenoside-Rd, as an inhibitor, remarkably inhibits Ca2+ entry
      through ROCC and SOCC without effects on VDCC and Ca2+ release in vascular smooth
      muscle cells.

PMID- 16973157
TI  - Tubulin ligands suggest a microtubule-NADPH oxidase relationship in postischemic
      cardiomyocytes.
AB  - Alterations of the microtubule network, which is involved in many vital
      processes, occur in several pathological conditions, such as cardiac ischemia.
      However, the connection between the microtubule assembly state and the factors
      affecting myocardial reperfusion injury, especially oxidative stress, is unknown.
      We aimed thus to study the effects of different tubulin ligands on the changes in
      the microtubule network and in several markers of cell injury and oxidative
      activity in cardiac muscle cells submitted to a reversible substrate-free,
      hypoxia-reoxygenation model of ischemia-reperfusion. The microtubule network was
      visualized by immunocytochemistry. Cell injury was evaluated via lactate
      dehydrogenase release and the mitochondrial function by the MTT test. Superoxide
      production was detected using dihydroethidium. The activity of NADPH oxidase and
      mRNA subunit expression were investigated. The microtubule disassembly induced by
      simulated ischemia was reversed by placing cardiomyocytes under normoxic
      conditions. This post-"ischemic" restoration of microtubule assembly was
      modulated by microtubule stabilizers (taxol: paclitaxel) and by microtubule
      disrupting drugs (nocodazole, colchicine). In addition, nocodazole decreased
      superoxide anion production as well as NADPH oxidase activity and mRNA expression
      of the NADPH oxidase subunit p22phox. These results demonstrated that the
      "ischemia"-induced microtubule network alteration is reversible and suggest a
      possible relationship between "reperfusion"-induced reassembly of microtubules
      and free radical generation in post-"ischemic" cardiomyocytes.

PMID- 16973158
TI  - Expression of the mRNA and protein of serine racemase in primary cultures of rat
      neurons.
AB  - Real-time quantitative PCR, Western blot and in situ hybridization techniques
      were employed to clarify the presence of serine racemase in the primary cultures
      of rat neurons. We have detected both serine racemase mRNA and protein in the
      cultured neurons. Both the mRNA and the protein levels in the neurons are higher
      than those in the astrocytes. Sequential detection of serine racemase mRNA and
      MAP2 immunoreactivity also revealed that serine racemase and MAP2 are co
      localized in the cultured neurons. These data are the first to demonstrate that a
      substantial amount of serine racemase exists in the cultured neurons.

PMID- 16973159
TI  - Relaxant effects of beta-adrenoceptor agonist formoterol and BRL 37344 on bovine
      iris sphincter and ciliary muscle.
AB  - We investigated the relaxant effect of beta2-adrenoceptor agonist formoterol and
      beta3-adrenoceptor agonist BRL 37344 on bovine iris sphincter and ciliary muscle
      and measured cAMP and cGMP levels. Iris sphincter (n = 16) and ciliary muscle (n
      = 16) strips were mounted in organ baths and tested for changes in isometric
      tension in response to formoterol and BRL 37344. Their relaxant effects on
      serotonin-induced contractions in the presence or absence of metoprolol, ICI
      118.551 and SR 59230A (beta1-, beta2-, beta3-adrenoceptor antagonist,
      respectively) were investigated. Their effects on cAMP and cGMP levels in iris
      sphincter (n = 12) and ciliary muscle (n = 12) were evaluated. Formoterol (10(
      11)-10(-5) M) and BRL 37344 (10(-10)-10(-5) M) decreased the serotonine-induced
      contractions in a concentration-dependent manner. Emax values of formoterol were
      significantly higher than those of BRL 37344 in iris sphincter and ciliary
      muscle, with no significant change in pD2 values. The relaxation responses by
      formoterol and BRL 37344 were antagonized with ICI 118.551 (10(-6) M) and SR
      59230A (10(-6) M). cAMP levels of formoterol- and BRL 37344-treated tissues were
      significantly higher than those of the control tissues. cGMP levels of BRL 37344
      treated tissues were significantly higher than those of control tissues, but this
      effect of BRL 37344 was less significant than its effect on cAMP levels. beta
      adrenoceptor relaxation responses in bovine iris sphincter and ciliary muscle are
      mediated by a mixed population of beta2- and beta3-adrenoceptor subtypes, with a
      predominant contribution of cAMP. Potency of formoterol and BRL 37344 was
      similar, but efficacy of formoterol was better than BRL 37344.

PMID- 16973160
TI  - Antisense oligonucleotide targeting c-fos mRNA limits retinal pigment epithelial
      cell proliferation: a key step in the progression of proliferative
      vitreoretinopathy.
AB  - The purpose of this work was to investigate the effect of c-fos antisense
      oligonucleotide (c-fos-AS-ON) on proliferative vitreoretinopathy (PVR). Cultures
      of human retinal pigment epithelial (hRPE) cells were established from adult
      human corneal donors. These cells were positively stained for cytokeratins. C-fos
      AS-ON effect on serum-stimulated cell proliferation was estimated by evaluating
      the incorporation of 5-bromo-2'-deoxy-uridine (BrdU) into cellular DNA. Reverse
      transcriptase polymerase chain reaction (RT-PCR) and Western blotting were
      respectively performed to quantify the serum-stimulated c-fos gene mRNA and
      protein expression in hRPE cells. Eight rabbits (16 eyes) were divided into c-fos
      AS-ON treatment group and control group. 2.5 x 10(5) cultured hRPE cells were
      injected into the vitreous cavity of eyes to establish a PVR model. Prevalence of
      PVR and retinal detachment were determined by indirect ophthalmoscopy on days 1,
      3, 7, 14, 21 and 28 post-injection and by pathological study on days 28 post
      injection. The results showed that blocking the expression of c-fos by the
      addition of c-fos-AS-ON to the culture medium significantly inhibited the hRPE
      cells proliferation. This effect of c-fos-AS-ON was found to be sequence specific
      (the use of a sense or a mismatch sense oligonucleotide had no such an effect)
      and dose-dependent (0.375 microM was the lowest effective dose tested). Growth
      inhibition by c-fos-AS-ON remained for at least 72 h. By using RT-PCR and Western
      blotting, we found that the c-fos-AS-ON could specifically inhibit c-fos mRNA and
      protein synthesis in cultured hRPE cells. Though the eyes injected with c-fos-AS
      ON also developed features of PVR, the severities of days 14, 21 and 28 post
      injection were significantly lower than those in the control eyes (P<0.05). We
      conclude that c-fos-AS-ON can inhibit cultured hRPE cell proliferation, which
      mechanism may relate to blocking the expression of c-fos and can reduce the
      prevalence of experimental PVR. These findings establish a rationale for
      investigating the potential use of a c-fos-AS-ON as a novel therapeutical tool in
      the treatment of PVR.

PMID- 16973161
TI  - Coiled-coil targeting of myocilin to intracellular membranes.
AB  - Mutations in myocilin (MYOC) associate with glaucoma and ocular hypertension.
      Unfortunately, the specific role of MYOC, a widely expressed protein of unknown
      function, in ocular hypertension is unknown. Since MYOC localizes both to
      intracellular membranes and to the cytosol, we tested the hypothesis that MYOC is
      a cytosolic protein that associates with cellular membranes via its coiled-coil
      domain. Using green fluorescent protein (GFP) chimeras in expression and
      metabolic labeling studies, we observed that MYOC's putative signal peptide
      failed to traffic GFP into the secretory machinery and out of transfected cells.
      Next, we tested which of MYOC's three folding domains were responsible for
      targeting. In cell fractionation and immunofluorescence microscopy studies, the
      coiled-coil, but not the helix-turn-helix or olfactomedin domains, was necessary
      and sufficient to target GFP chimeras to cell membranes. Interestingly, a
      vesicular phenotype required sequential addition of the helix-turn-helix and
      olfactomedin domains to the coiled-coil. Taken together, these data indicate that
      the coiled-coil domain, not the putative signal sequence, is responsible for the
      targeting of MYOC to the secretory machinery.

PMID- 16973162
TI  - Gamma glutamyl transpeptidase is a dynamic indicator of endothelial response to
      stroke.
AB  - Gamma glutamyl transpeptidase (gammaGT) is enriched at the apical surface of the
      cerebral capillaries that constitute the blood-brain barrier (BBB). This study
      tested the effects of hypoxia and inflammation on gammaGT activity in mice after
      stroke induced by transient cerebral artery occlusion (tMCAO) and in cultured
      cerebral microvessel endothelial cells. In microvessel-enriched preparations from
      mice after tMCAO, gammaGT activity was higher than in the sham controls in both
      ipsilateral and contralateral hemispheres from 12 h to 5 days after stroke, but
      lower at later time points (10-15 days). To identify the roles of different
      cytotoxic and stimulatory signals in this event, we further studied the dynamic
      changes of gammaGT activity in rat brain endothelial (RBE4) cells. Tumor necrosis
      factor alpha and lipopolyssachride significantly increased gammaGT activity in a
      time-dependent manner, an effect not seen after re-oxygenation. Such endothelial
      activation correlated with reduced total cellular ATP production. Thus, hypoxia
      and inflammatory stimulation appeared to have opposite effects on endothelial
      function. With the co-existence of inflammation and hypoxia in the brain after
      ischemic stroke, dynamic changes of gammaGT activity reflect evolving changes of
      endothelial function.

PMID- 16973163
TI  - Efficacy of an essential oil of Eugenia caryophyllata against Psoroptes cuniculi.
AB  - The acaricidal activity of Eugenia caryophyllata essential oil was evaluated in
      vitro and in vivo on Psoroptes cuniculi, a mange mite. In vitro, different
      concentrations of the oil were tested and the observed mites mortality was
      compared with that observed in untreated and treated (Acacerulen R) controls. In
      vivo, six P. cuniculi infected rabbits were topically treated with the oil
      diluted at 2.5% and compared with untreated and treated control groups of six
      rabbits each. In vitro, up to the concentration of 0.10% the oil gave highly
      significant (P<0.01) percentages of mite mortality respect to the untreated
      controls, but only up to 0.16% it showed the same efficacy of Acacerulen R. In
      vivo, the treatment with the essential oil cured all infested rabbits and no
      statistical differences were observed respect to the treated control group. The
      untreated rabbits remained infested.

PMID- 16973164
TI  - Barth syndrome, a human disorder of cardiolipin metabolism.
AB  - Barth syndrome is an X-linked recessive disease caused by mutations in the
      tafazzin gene. Patients have reduced concentration and altered composition of
      cardiolipin, the specific mitochondrial phospholipid, and they have variable
      clinical findings, often including heart failure, myopathy, neutropenia, and
      growth retardation. This article provides an overview of the molecular basis of
      Barth syndrome. It is argued that tafazzin, a phospholipid acyltransferase, is
      involved in acyl-specific remodeling of cardiolipin, which promotes structural
      uniformity and molecular symmetry among the cardiolipin molecular species.
      Inhibition of this pathway leads to changes in mitochondrial architecture and
      function.

PMID- 16973165
TI  - The evolving trends in the care of polytrauma.

PMID- 16973166
TI  - Intentional and unintentional medication non-adherence: a comprehensive framework
      for clinical research and practice? A discussion paper.
AB  - Non-adherence to medications is a prevalent and persistent healthcare problem,
      particularly for patients with a chronic disorder. Researchers have endeavoured
      to address poor adherence for the past five decades resulting in the accumulation
      of a vast body of literature. Despite the enormity of research conducted,
      interventions to date have neither been cost-effective nor predictably clinically
      effective in enhancing medication adherence. Though concerning, such contemporary
      information serves to refocus attention on the adequacy of knowledge regarding
      the factors influencing medication non-adherence. Although little consensus
      exists regarding the optimal categorisation of these influencing factors,
      increasingly, the broad and 'all encompassing' categorisation of intentional and
      unintentional factors is being used to account for patient medication-taking
      behaviours and actions. An extensive review of the related literature provides
      the basis for a critical discussion on the value and comprehensiveness of this
      current classification in guiding future adherence research and consequent
      clinical interventions. An appraisal of this categorisation is important if
      decisions regarding interventions are not to be made in a vacuum of insufficient
      understanding, which would result in the continued ineffective use and
      distribution of valuable resources to combat non-adherence.

PMID- 16973167
TI  - Striving for balance: a grounded theory study of health experiences of nurses
      with musculoskeletal problems.
AB  - BACKGROUND: Musculoskeletal disorders (MSD) are one of the major causes of the
      high levels of long-term sickleave and early retirement, and healthcare personnel
      are among the occupational groups most affected. Only limited research in the
      area has focused on the experiences of those affected, and to increase the
      understanding of MSD, all dimensions of the health experiences need to be taken
      into consideration. OBJECTIVES: The aim of this paper was to explore the
      experiences of illness and wellness among female healthcare personnel with
      musculoskeletal symptoms. DESIGN: A qualitative grounded theory approach guided
      the study in data collection and analysis. SETTINGS: Medical and surgical ward
      units at three hospitals; one university hospital and two minor hospitals.
      PARTICIPANTS: Eight women, registered nurses and nursing aides, with neck,
      shoulder and/or back problems in early stages. METHODS: A grounded theory
      approach was used with narrative thematic interviews and parallel data analysis
      with constant comparisons. RESULTS: The analysis revealed a process of striving
      to reach a balance between illness and wellness, through accepting and handling
      illness. Illness appeared as a threat and an experience, while experiences of
      wellness were simultaneously nurtured. The informants were striving for balance
      through an inner reasoning leading to acceptance and by handling illness in
      various ways depending on the character of the illness. CONCLUSION: This paper
      indicates the diversity of the illness experience, the parallel importance of
      wellness, and the process of balancing these two in order to feel well enough. As
      previous research has shown that MSD has a multifactorial cause, a holistic view
      of health promotion, prevention and rehabilitation may provide a more effective
      tool than the bodily physical focus most frequently used today.

PMID- 16973168
TI  - Effects of arsenic exposure and genetic polymorphisms of p53, glutathione S
      transferase M1, T1, and P1 on the risk of carotid atherosclerosis in Taiwan.
AB  - To evaluate the joint effects between genetic polymorphisms of glutathione S
      transferase M1, T1, P1, and p53, and arsenic exposure through drinking well water
      on the risk of carotid atherosclerosis, 605 residents including 289 men and 316
      women were recruited from a northeastern area of Taiwan. Carotid atherosclerosis
      was diagnosed by either a carotid artery intima-media thickness (IMT) of >1.0 mm,
      a plaque score of > or =1, or stenosis of >50%. A significant age- and gender
      adjusted odds ratio of 3.3 for the development of carotid atherosclerosis was
      observed among the high-arsenic exposure group who drank well water containing
      arsenic at levels >50 microg/L. The high-arsenic exposure group with GSTP1
      variant genotypes of Ile/Val and Val/Val, and with the p53 variant genotypes of
      Arg/Pro and Pro/Pro had 6.0- and 3.1-fold higher risks of carotid
      atherosclerosis, respectively. In addition, the high-arsenic exposure group with
      one or two variant genotypes of GSTP1 and p53 had 2.8- and 6.1-fold higher risks
      of carotid atherosclerosis, respectively, and showed a dose-dependent
      relationship. A multivariate-adjusted odds ratio of 3.4 for the risk of carotid
      atherosclerosis among study subjects with the two variant genotypes of GSTP1 and
      p53 was also found. Our study showed the joint effects on the risk of carotid
      atherosclerosis between the genetic polymorphisms of GSTP1 and p53, and arsenic
      exposure.

PMID- 16973169
TI  - RhoA-dependent PAI-1 gene expression induced in endothelial cells by monocyte
      adhesion mediates geranylgeranyl transferase I and Ca2+ signaling.
AB  - We investigated the role of RhoA activation and its mechanism in plasminogen
      activator inhibitor-1 (PAI-1) gene expression induced in endothelial cells by
      monocyte adhesion. Isolated human peripheral blood monocytes were added to
      cultured human coronary endothelial cells. Monocyte adhesion to endothelial cells
      increased PAI-1 expression at the transcriptional level and activated RhoA which
      was accompanied by an increase in the activity of geranylgeranyl transferase I
      (GGTase I), an enzyme responsible for geranylgeranylation, and actin stress fiber
      formation. Inhibition of RhoA by C3 exoenzyme or by adenovirus-mediated
      expression of N19RhoA, as well as by pravastatin, prevented the upregulation of
      PAI-1 induced by monocyte adhesion. GGTI-286, an inhibitor of GGTase I, prevented
      the monocyte-induced RhoA activation and PAI-1 expression in endothelial cells.
      Monocyte attachment induced an increase in intracellular Ca(2+) concentration
      ([Ca(2+)](i)) in endothelial cells and Ca(2+) chelation prevented the increased
      promoter activity and expression of PAI-1 induced by monocyte adhesion. C3
      exoenzyme and GGTI-286 also suppressed endothelial intracellular Ca(2+)
      mobilization and Ca(2+) entry induced by monocytes. The present study shows that
      GGTase I plays a role in the RhoA activation in endothelial cells induced by
      monocyte adhesion and that GGTase I-mediated Ca(2+) signaling may contribute to
      RhoA-dependent PAI-1 gene expression.

PMID- 16973170
TI  - Chronic hyperbaric oxygen treatment elicits an anti-oxidant response and
      attenuates atherosclerosis in apoE knockout mice.
AB  - We previously demonstrated that hyperbaric oxygen (HBO) treatment inhibits diet
      induced atherosclerosis in New Zealand White rabbits. In the present study we
      investigate the mechanisms that might be involved in the athero-protective effect
      of HBO treatment in a well-accepted model of atherosclerosis, the apoE knockout
      (KO) mouse. We examine the effects of daily HBO treatment (for 5 and 10 weeks) on
      the components of the anti-oxidant defense mechanism and the redox state in
      blood, liver and aortic tissues and compare them to those of untreated apoE KO
      mice. HBO treatment results in a significant reduction of aortic cholesterol
      content and decreased fatty streak formation. These changes are accompanied by a
      significant reduction of autoantibodies against oxidatively modified LDL and
      profound changes in the redox state of the liver and aortic tissues. A 10-week
      treatment significantly reduces hepatic levels of TBARS and oxidized glutathione,
      while significantly increases the levels of reduced glutathione, glutathione
      reductase (GR), transferase, Se-dependent glutathione peroxidase and catalase
      (CAT). The effects of HBO treatment are similar in the aortic tissues. These
      observations provide evidence that HBO treatment has a powerful effect on the
      redox state of relevant tissues and produces an environment that inhibits
      oxidation. The anti-oxidant response may be the key to the anti-atherogenic
      effect of HBO treatment.

PMID- 16973171
TI  - Identification, quantitation and method validation for the analysis of suspected
      allergens in fragrances by comprehensive two-dimensional gas chromatography
      coupled with quadrupole mass spectrometry and with flame ionization detection.
AB  - The first part of this study first aims at validating a method to identify
      suspected allergens limited by EU regulations in fragrances by comprehensive two
      dimensional gas chromatography (GC x GC) coupled with rapid scanning quadrupole
      MS (GC x GC-qMS). The effectiveness of the quadrupole MS operating at different
      scanning speed (1000 and 11,111 amu/s) was evaluated in identifying (full scan
      mode acquisition--TIC) and in quantifying (single ion monitoring--SIM) the target
      analytes in complex mixtures. In full scan acquisition mode the mass range was
      reduced to 40-240 amu to increase the scan acquisition rate while in SIM mode the
      influence of different dwell-times (40, 10 and 5 ms) was tested. The number of
      scans for each single modulated chromatographic GC x GC peak and the total number
      of scans for the 2D peak, together with half height peak width (referred to apex)
      of each allergen in the standard mixture in both TIC and SIM modes were
      determined. Moreover, the match quality of the spectra obtained by GC/MS at 1000
      and 11,111 amu/s and by GC x GC-MS at 11,111 amu/s were compared and the
      occurrence of spectral skewing verified. In the second part of this work
      quantitative methods by GC x GC-SIM/qMS and GC x GC-FID were validated on the
      basis of Eurachem/CITAC protocols through which the following performance
      parameters were determined: confirmation of identity, selectivity and
      specificity, limit of detection (LOD), limit of quantitation (LOQ), linearity
      (working and linear range), precision and accuracy and uncertainty. Suspected
      allergens were spiked in a concentration range between 2 and 25 ppm (microg/mL)
      on a Test fragrance taken as a reference, while 1,4 dibromo-benzene and 4,4'
      dibromodiphenyl were used as internal standards.

PMID- 16973172
TI  - Rapid assessment of the antigenic integrity of tetrameric HLA complexes by human
      monoclonal HLA antibodies.
AB  - The ability of tetrameric major histocompatibility complex (MHC) class I-peptide
      complexes (tetramers) to detect antigen-specific T lymphocyte responses has
      yielded significant information about the generation of in vivo immunity in
      numerous antigenic systems. Here we present a novel method for rapid validation
      of tetrameric HLA molecules based on the presence of allodeterminants. Human
      monoclonal antibodies (mAbs) recognizing polymorphic determinants on HLA class I
      were immobilized on polystyrene microparticles and used to probe the structural
      integrity of tetrameric HLA class I molecules by flow cytometry. A total of 22
      tetramers, based on HLA-A1, A2, A3, A24, B7 and B8 were reactive with their
      counterpart mAbs, thus confirming their antigenic integrity. A positive outcome
      of this mAb test ensures that tetrameric HLA class I can be used with greater
      confidence in subsequent functional assays.

PMID- 16973173
TI  - Natural co-infection of Babesia caballi and Encephalitozoon-like microsporidia in
      the tick Anocentor nitens (Acari: Ixodidae).
AB  - The present paper reports the occurrence of natural co-infection of Babesia
      caballi and Encephalitozoon-like microsporidia in the tick Anocentor nitens.
      Engorged females of ticks, collected from a naturally B. caballi-infected horse,
      were incubated at 27 degrees C and relative humidity over 83%. After a 6-day
      incubation period, Giemsa-stained smears prepared from hemolymph were examined
      microscopically under oil immersion. B. caballi infected ticks were dissected and
      samples of midgut tissue were examined by transmission electron microscopy,
      through which free sporokinetes were seen in the cytoplasm of gut epithelial
      cells. In addition, Encephalitozoon-like microsporidia were observed inside the
      parasitophorous vacuoles in the same cell in which sporokinetes of B. caballi
      were found and also in some neighbour cells. They presented different
      morphological stages, suggesting a sequential phases of development.

PMID- 16973174
TI  - Effective engraftment but poor mid-term persistence of mononuclear and
      mesenchymal bone marrow cells in acute and chronic rat myocardial infarction.
AB  - Bone marrow cells are used with promising results for cell therapy after
      myocardial infarction (MI). We determined the survival and organ distribution of
      transplanted mononuclear (MNC) or mesenchymal (MSC) bone marrow cells, and the
      influence of cell type, cell number and application time. MNC and MSC (male
      Fischer 344 rats) were injected into the border zone of MI (syngeneic females)
      immediately or 7 days after LAD ligation (10(5) or 10(6) cells, 50 microl). After
      0 h, 48 h, 5 days, 3 weeks and 6 weeks, DNA of heart, lung, liver, spleen,
      kidney, blood, bone marrow, brain and skeletal muscle was isolated and the number
      of donor cells determined by quantitative real-time PCR with Y-chromosome
      specific primers (each n>or=4). The percentage of donor-cells in the heart
      decreased rapidly from 34-80% of injected cells (0 h) to 0.3-3.5% (6 weeks)
      independent from cell type, number and application time. The absolute number
      increased after increasing injected cell number (10(6) vs. 10(5)). In the lung,
      MNC and MSC were found at 0 h (126+/-48 and 140+/-3 per million organ cells), but
      in liver and kidney, only few. At 48 h and 6 weeks, an increasing number of MNC,
      but not MSC, were detected in the spleen (6 weeks, 602+/-173 per million organ
      cells vs. 95+/-50 in the heart, P=0.02). In all other organs, only few or no
      grafted cells of either cell type were detected at these times. Organ
      distribution was independent from injection time. The low survival of grafted
      cells may limit their therapeutic impact, while their distribution to other
      organs must be considered in all cell therapy applications.

PMID- 16973175
TI  - Sequence motifs and antimotifs in beta-barrel membrane proteins from a genome
      wide analysis: the Ala-Tyr dichotomy and chaperone binding motifs.
AB  - Beta-barrel membrane proteins are found in the outer membrane of gram-negative
      bacteria, mitochondria, and chloroplasts. Although sequence motifs have been
      studied in alpha-helical membrane proteins and have been shown to play important
      roles in their assembly, it is not clear whether over-represented motifs and
      under-represented anti-motifs exist in beta-barrel membrane proteins. We have
      developed probabilistic models to identify sequence motifs of residue pairs on
      the same strand separated by an arbitrary number of residues. A rigorous
      statistical model is essential for this study because of the difficulty
      associated with the short length of the strands and the small amount of
      structural data. By comparing to the null model of exhaustive permutation of
      residues within the same beta-strand, propensity values of sequence patterns of
      two residues and p-values measuring statistical significance are calculated
      exactly by several analytical formulae we have developed or by enumeration. We
      find that there are characteristic sequence motifs and antimotifs in
      transmembrane (TM) beta-strands. The amino acid Tyr plays an important role in
      several such motifs. We find a general dichotomy consisting of favorable
      Aliphatic-Tyr sequence motifs and unfavorable Tyr-Aliphatic antimotifs. Tyr is
      also part of a terminal motif, YxF, which is likely to be important for chaperone
      binding. Our results also suggest several experiments that can help to elucidate
      the mechanisms of in vitro and in vivo folding of beta-barrel membrane proteins.

PMID- 16973176
TI  - Modularity of the transcriptional response of protein complexes in yeast.
AB  - A comprehensive study is performed on the condition-dependent expression of genes
      coding for the components of hand curated multi-protein complexes of the yeast
      Saccharomyces cerevisiae, in order to identify coherent transcriptional modules
      within these complexes. Such modules are defined as groups of genes within
      complexes whose expression profiles under a common set of experimental conditions
      allow us to discriminate them from random sets of genes. Our analysis reveals
      that complexes such as the cytoplasmic ribosome, the proteasome and the
      respiration chain complexes previously characterized as "stable" or "permanent"
      represent transcriptional modules that are coherently up or down-regulated in
      many different conditions. Overall however, some level of coherent expression is
      detected only in 71 out of the total of 113 complexes with at least five
      different protein components that could be reliably analyzed. Of these, 26 behave
      as coherently expressed transcriptional modules encompassing all the components
      of the complex. In another 15, at least half of the components make up such
      modules and in ten, few or no modules are detected. In an additional 20 complexes
      coherent expression is detected, but in too few conditions to enable reliable
      module detection. Interestingly, the transcriptional modules, when detected,
      often correspond to one or more known sub-complexes with specific functions.
      Furthermore, detected modules are generally consistent with transcriptional
      modules identified on the basis of predicted cis-regulatory sequence motifs.
      Also, groups of genes shared between complexes that carry out related functions
      tend to be part of overlapping transcriptional modules identified in these
      complexes. Together these findings suggest that transcriptional modules may
      represent basic functional and evolutionary building blocs of protein complexes.

PMID- 16973177
TI  - Two cases of spontaneous middle cerebral arterial dissection causing ischemic
      stroke.
AB  - Spontaneous middle cerebral arterial dissection (MCAD) is a rare cause of
      ischemic stroke. We report two cases of isolated spontaneous MCAD causing
      ischemic stroke. MCAD should be considered when a young patient has a middle
      cerebral artery territory infarct with stenosis at the origin of the middle
      cerebral artery. We discuss noninvasive radiological techniques for the diagnosis
      of MCAD.

PMID- 16973178
TI  - Multiscale model for pulmonary oxygen uptake and its application to quantify
      hypoxemia in hepatopulmonary syndrome.
AB  - This paper presents a novel multiscale methodology for quantitative analysis of
      pulmonary gas exchange. The process of oxygen uptake in the lungs is a complex
      multiscale process, characterized by multiple time and length scales which are
      coupled nonlinearly through the processes of diffusion, convection and reaction,
      and the overall oxygen uptake is significantly influenced by the transport and
      reaction rate processes at the small-scales. Based on the separation of length
      scales, we characterize these disparate scales by three representative ones,
      namely micro (red blood cell), meso (capillary and alveolus) and macro (lung). We
      start with the fundamental convection-diffusion-reaction (CDR) equation that
      quantifies transport and reaction rates at each scale and apply spatial averaging
      techniques to reduce the dimensionality of these models. The resultant low
      dimensional models embed each scale hierarchically within the other while
      retaining the important parameters of the small-scales in the averaged equations,
      and drastically reduce the computational efforts involved in solving them. We use
      our multiscale model for pulmonary gas exchange to quantify the oxygen uptake
      abnormalities in patients with hepatopulmonary syndrome (HPS), a disease which is
      characterized by coupled abnormalities in multiple length scales. Based on our
      multiscale modeling, we suggest a strategy to stratify patients with HPS into two
      categories--those who are oxygen-responsive and those who are oxygen non
      responsive with intractable hypoxemia.

PMID- 16973179
TI  - Identification of avarol derivatives as potential antipsoriatic drugs using an in
      vitro model for keratinocyte growth and differentiation.
AB  - Avarol, a marine sesquiterpenoid hydroquinone, and 14 avarol derivatives have
      shown interesting anti-inflammatory properties in previous studies. In this
      study, avarol and derivatives were evaluated in high-throughput keratinocyte
      culture models using cytokeratin 10 and SKALP/Elafin expression as markers for
      respectively normal and psoriatic differentiation. Avarol and five of its
      derivatives (5, 10, 13, 14 and 15) were selected for further study. Only 10, 13,
      14 and 15 were able to inhibit keratinocyte cell growth. Changes in expression
      levels of 22 genes were assessed by quantitative real time PCR (qPCR). From these
      genes, TNFalpha mRNA levels showed the strongest changes. For compound 13, 15 and
      dithranol (used as a model antipsoriatic drug), a dose-dependent downregulation
      of TNFalpha mRNA was found. The changes in TNFalpha mRNA were confirmed at the
      protein level for compound 13. Additionally, this compound was able to reduce
      also IL-8 and COX-2 mRNA levels and this effect was correlated with a reduction
      in COX-2 protein expression. The mechanism of action of this compound involves at
      least the inhibition of NF-kappaB-DNA binding activity. In conclusion, our high
      throughput screening models in combination with quantitative assessment of
      changes in gene expression profiles identified the avarol derivative 13, a
      benzylamine derivative of avarol at the 4' position of benzoquinone ring, as an
      interesting anti-psoriatic drug candidate that inhibits keratinocyte cell growth
      and TNFalpha and COX-2 expression.

PMID- 16973180
TI  - Abnormally speeded saccades to ipsilesional targets in patients with spatial
      neglect.
AB  - We mapped the distribution of saccadic reaction times (SRTs) in the visual field
      of patients with spatial neglect in order to characterise the topography of the
      bias in spatial orientation peculiar to this disorder. LED-generated stimuli were
      lit randomly in one of four positions (+/-5 degrees , +/-10 degrees , +/-20
      degrees , +/-30 degrees ) along the horizontal meridian in blocks of either
      ipsilesional or contralesional presentations. Patients were asked to move the
      gaze as quickly as possible from central fixation to target upon its appearance.
      Unlike control subjects, patients with neglect showed an asymmetric distribution
      of visuo-motor performance in the two hemifields with an increasing impairment in
      target detection and saccadic reaction at increasing eccentricities in the
      contralesional field. In contrast, in the ipsilesional field they showed
      abnormally speeded SRTs at 5 degrees and 10 degrees , outperforming even healthy
      subjects. Latency of saccades increased again at more peripheral ipsilesional
      locations (20 degrees and 30 degrees ) where there was also a tendency for a
      higher omission rate as compared to control groups. These results indicate that
      in neglect patients the spatial orientation bias, as witnessed by saccadic
      performance, specifically affects an off-centred sector of the ipsilesional
      space, and this is in keeping with evidence from a previous study using a manual
      RT paradigm. The generality of this phenomenon across different types of motor
      response suggests that it depends upon abnormal mechanisms of spatial coding
      interfering with perceptual processing and orienting behaviour.

PMID- 16973181
TI  - Seeing trees OR seeing forests in simultanagnosia: attentional capture can be
      local or global.
AB  - Patients with simultanagnosia often demonstrate 'local capture', meaning that
      they identify only the local elements of stimuli that contain a hierarchy of both
      local and global structures. Recent studies, however, have found that these
      patients may implicitly process the global form. We examined the general
      applicability of the concept of local capture, and specifically whether the
      global level of stimuli can be explicitly reported by patients with
      simultanagnosia. We tested a patient with simultanagnosia with globally biased
      stimuli such as hierarchical Arcimboldo faces and small, dense Navon letters.
      With Arcimboldo faces our patient often reported only the face and not the local
      elements--the first demonstration of global rather than local capture. With Navon
      letters, the patient's ability to report the global letter varied with stimulus
      density and inversely with stimulus size, so that local capture was found only
      with large and sparse stimuli. With both faces and letters, the likelihood of
      global capture by the patient was related to the ease of global reporting in
      controls, as indexed by their reaction times. This suggests that the patient's
      global perception is influenced by the same factors operating in healthy
      individuals. We conclude that attentional capture in simultanagnosia can be
      either global or local. Capture likely occurs because of a pathological
      restriction and/or rigidity of attention, but the type of capture depends upon
      the competitive balance between global and local salience.

PMID- 16973183
TI  - Time course of alterations after olfactory bulbectomy in mice.
AB  - Olfactory bulbectomy in rodents causes behavioral alterations, which result in a
      model of depression, validated for pharmacological screening of antidepressant
      drugs. To unravel the appearance and time course of the major behavioral effects
      which follow surgery, mice underwent olfactory bulb ablation or sham operation,
      and were analyzed after 1, 2, or 4 weeks. Bulbectomized (BX) mice were anosmic,
      and hyperactive when tested under stressful situations in the forced swimming
      test. Predatory aggression was upregulated in a time-dependent way: only after 4
      weeks BX mice were faster than controls in attacking prey. At the same time, they
      were less aggressive against intruders; they did not differ from controls in open
      field exploration, but displayed a cognitive impairment in water maze. Behavioral
      tests thus indicated a marked hyperreactivity, a dissociation among different
      aggressive behaviors, and also a cognitive impairment induced by bulbectomy.
      Histological confirmation of the damage revealed that major modifications took
      place in the rostral pole of frontal lobes, with a significant increase in the
      width of the rostral migratory stream, 2 weeks after surgery, and in the
      subventricular zone, 4 weeks after surgery. These results suggest a base for the
      time-course of appearance of behavioral symptoms in BX mice.

PMID- 16973184
TI  - nNOS is involved in behavioral thermoregulation of newborn rats during hypoxia.
AB  - The present study was undertaken to investigate the role of nitric oxide (NO)
      pathway in the behavioral thermoregulation of newborn rats in cold and hypoxia.
      We predicted that injection of L-NAME (non-selective NO synthase (NOS) inhibitor)
      and SMTC (neuronal NOS (nNOS) inhibitor) would restore the huddling behavior and
      eliminate the reduction of Tb caused by hypoxia. Experiments were performed on
      Wistar rat pups of 7-9 days old. We measured Tb and analyzed the huddling
      behavior by means of the calculation of the total surface area occupied by 5 pups
      and the number of single pups grouped in the center of a chamber at 20 degrees C,
      before and after L-NAME, SMTC or their respective vehicles (D-NAME and saline)
      s.c. injections. Subsequently, the pups were exposed to hypoxia (10% O(2)) during
      30 min, whereas control animals were kept under normoxia. The experiments were
      monitored by a digital camera. All animals were hypothermic when exposed to 20
      degrees C. There was no significant difference in Tb, total area and number of
      single pups in normoxia after treatments. During hypoxia, the drop in Tb was
      higher in control groups, and this effect was attenuated by L-NAME and SMTC
      injections. Hypoxia increased the area occupied by the pups in saline, D-NAME and
      L-NAME groups, while SMTC attenuated this response. The data indicate that NO
      pathway is involved in the inhibition of huddling behavior and in the reduction
      of Tb caused by hypoxia, but plays no role during normoxia. Furthermore, NO seems
      to arise from the nNOS isoform.

PMID- 16973185
TI  - Polyethylene glycol fractionation improved detection of low-abundant proteins by
      two-dimensional electrophoresis analysis of plant proteome.
AB  - Poor detection of low-abundant proteins is a common problem in two-dimensional
      electrophoresis (2-DE) for separation of proteins in a proteome analysis. This is
      attributed partially, at least, to the existence of high-abundant proteins, e.g.
      ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) in plants. They engage
      a large proportion of the whole-cell proteins and thus prevent low-abundant
      proteins from being up-taken by immobilized pH gradient (IPG) strip, consequently
      making the latter poorly detectable by 2-DE. In this work, we report a
      straightforward protocol for preparation of whole-cell proteins through
      differential polyethylene glycol (PEG) precipitation aiming at elimination of
      Rubisco from plant protein samples. In comparison with 2-DE analysis of protein
      samples prepared using a conventional TCA/acetone method, a relatively high
      reproducibility of proteins was achieved using a PEG fractionation protocol in
      terms of protein yield and protein species. As expected, the large subunit of
      Rubisco was precipitated predominantly in the 16% PEG fraction. This allowed
      proteins of the Rubisco-containing fraction to be analyzed separately from those
      of other PEG fractions. After taking into account the overlapping protein spots
      among 2-DE gels of all fractions through image and statistical analyses, we
      detected with this protocol a total 5077 protein spots, among which ca. 80% are
      proteins undetectable with the TCA/acetone method, while the rest of proteins
      exhibited a significant increase in their abundance. This protocol was developed
      using Arabidopsis as a source of protein and thus may also be applicable to
      protein preparations of other plants.

PMID- 16973186
TI  - Purification and characterization of selenium-containing phycocyanin from
      selenium-enriched Spirulina platensis.
AB  - A fast protein liquid chromatographic method for purification of selenium
      containing phycocyanin (Se-PC) from selenium-enriched Spirulina platensis was
      described in this study. The purification procedures involved fractionation by
      ammonium sulfate precipitation, DEAE-Sepharose ion-exchange chromatography and
      Sephacry S-300 size exclusion chromatography. The purity ratio (A620/A280) and
      the separation factor (A620/A655) of the purified Se-PC were 5.12 and 7.92,
      respectively. The Se concentration of purified Se-PC was 496.5 microg g(-1)
      protein, as determined by ICP-AES analysis. The purity of the Se-PC was further
      characterized by UV-VIS and fluorescence spectrometry, SDS-PAGE, RP-HPLC and gel
      filtration HPLC. The apparent molecular mass of the native Se-PC determined by
      gel filtration HPLC was 109 kDa, indicating that the protein existed as a trimer.
      SDS-PAGE of the purified Se-PC yielded two major bands corresponding to the alpha
      and beta subunits. A better separation of these two subunits was obtained by RP
      HPLC. Identification of the alpha and beta subunits separated by SDS-PAGE and RP
      HPLC was achieved by peptide mass fingerprinting (PMF) using MALDI-TOF-TOF mass
      spectrometry.

PMID- 16973187
TI  - Chemical constituents of Malagasy liverworts: cyclomyltaylanoids from Bazzania
      madagassa.
AB  - Five cyclomyltaylanoids (2-6), together with 1R,5R-diacetoxycyclomyltaylan-10-one
      (1), (+)-globulol, and ent-4beta,10alpha-dihydroxyaromadendrane have been
      isolated from the diethyl ether fraction of the Malagasy liverwort, Bazzania
      madagassa. The structure of 1 was confirmed by X-ray analysis, while those of the
      compounds were established on the basis of one- and two-dimensional NMR
      spectroscopic evidence, and comparison with data reported in the literature. The
      chemosystematics of B. madagassa are discussed.

PMID- 16973188
TI  - Polyphenol oxidases in plants and fungi: going places? A review.
AB  - The more recent reports on polyphenol oxidase in plants and fungi are reviewed.
      The main aspects considered are the structure, distribution, location and
      properties of polyphenol oxidase (PPO) as well as newly discovered inhibitors of
      the enzyme. Particular stress is given to the possible function of the enzyme.
      The cloning and characterization of a large number of PPOs is surveyed. Although
      the active site of the enzyme is conserved, the amino acid sequence shows very
      considerable variability among species. Most plants and fungi PPO have multiple
      forms of PPO. Expression of the genes coding for the enzyme is tissue specific
      and also developmentally controlled. Many inhibitors of PPO have been described,
      which belong to very diverse chemical structures; however, their usefulness for
      controlling PPO activity remains in doubt. The function of PPO still remains
      enigmatic. In plants the positive correlation between levels of PPO and the
      resistance to pathogens and herbivores is frequently observed, but convincing
      proof of a causal relationship, in most cases, still has not been published.
      Evidence for the induction of PPO in plants, particularly under conditions of
      stress and pathogen attack is considered, including the role of jasmonate in the
      induction process. A clear role of PPO in a least two biosynthetic processes has
      been clearly demonstrated. In both cases a very high degree of substrate
      specificity has been found. In fungi, the function of PPO is probably different
      from that in plants, but there is some evidence indicating that here too PPO has
      a role in defense against pathogens. PPO also may be a pathogenic factor during
      the attack of fungi on other organisms. Although many details about structure and
      probably function of PPO have been revealed in the period reviewed, some of the
      basic questions raised over the years remain to be answered.

PMID- 16973189
TI  - Caryophyllene-rich rhizome oil of Zingiber nimmonii from South India: Chemical
      characterization and antimicrobial activity.
AB  - Volatile oil from the rhizomes of Zingiber nimmonii (J. Graham) Dalzell was
      isolated, characterized by analytical gas chromatography and gas chromatography
      mass spectroscopy. Sixty-five constituents accounting for 97.5% of the oil were
      identified. Z. nimmonii rhizome oil is a unique caryophyllene-rich natural source
      with isomeric caryophyllenes, beta-caryophyllene (42.2%) and alpha-humulene
      (alpha-caryophyllene, 27.7%), as its major constituents along with traces of
      isocaryophyllene. The rhizome oil contained 71.2% sesquiterpenes, 14.2%
      oxygenated sesquiterpenes, 8.9% monoterpenes, 1.9% oxygenated monoterpenes and
      1.3% non-terpenoid constituents. The antimicrobial activity of the oil was tested
      against human and plant pathogenic bacteria and fungi. The oil showed significant
      inhibitory activity against the fungi, Candida glabrata, C. albicans and
      Aspergillus niger and the bacteria Bacillus subtilis and Pseudomonas aeruginosa.
      No activity was observed against the fungus Fusarium oxysporum.

PMID- 16973190
TI  - Oleanane-type triterpenes of Embelia schimperi leaves.
AB  - An investigation of an ethyl acetate extract of Embelia schimperi leaves has led
      to the isolation of 10 oleanane-type triterpenes characterized as 3beta,16alpha
      di-O-acetyl-13beta, 28-epoxyoleanane (1), 3beta-acetyl-16-oxo-13beta, 28
      epoxyoleanane (2), 3beta-acetyl-16alpha-hydroxy-13beta, 28-epoxyoleanane (3),
      3beta-acetyl-16alpha-hydroxyoleanane-13beta, 28-olide (4), 3beta-acetyl-28
      hydroxy-16-oxo-12-oleanene (5), 3beta, 28-di-O-acetyl-16alpha-hydroxy-12-oleanene
      (6), 3beta-acetyl-11alpha, 28-dihydroxy-16-oxo-12-oleanene (7), 3beta, 11alpha,
      16alpha, 28-tetrahydroxy-12-oleanene (8), 3beta-acetyl-16alpha, 28alpha-dihydroxy
      13beta, 28-oxydooleanane (9) and 3beta, 28alpha-dihydroxy-16-oxo-13beta, 28
      oxydooleanane (10). The known compounds isolated from the same extract included
      3beta, 16alpha-dihydroxy-13beta, 28-epoxyoleanane (protoprimulagenin A) (11),
      3beta-hydroxy-16-oxo-13beta, 28-epoxyoxyoleanane (aegicerin) (12), 3, 16-dioxo
      13beta, 28-epoxyoleanane (embilionone) (13), 3beta, 28-dihydroxy-16-oxo-12
      oleanene (schimperinone) (14), taraxerone (15), taraxerol (16) and stigmasterol
      (17). Structure elucidations were carried out spectroscopically.

PMID- 16973191
TI  - Chromenes from Peperomia serpens (Sw.) Loudon (Piperaceae).
AB  - Chromatographic separation of the CH2Cl2 extract from leaves of Peperomia serpens
      yielded two chromenes [5-hydroxy-8-(3',7'-dimethylocta-2',6'-dienyl)-2,2,7
      trimethyl-2H-1-chromene (1) and 5-hydroxy-8-(3'-methyl-2'-butenyl)-2,2,7
      trimethyl-2H-1-chromene-6-carboxylic acid (2)], besides the known chromene
      [methyl 5-hydroxy-2,2,7-trimethyl-2H-1-chromene-6-carboxylate (3)] and the
      flavonoid, dihydrooroxylin (4). Their structural elucidation were achieved by
      spectroscopic analyses. The antifungal activities of the CH2Cl2 extract and the
      isolated chromenes were measured bioautographically against Cladosporium
      cladosporioides and C. sphaerospermum, when it was found that the crude extract
      showed higher activity as compared to the pure compounds.

PMID- 16973192
TI  - 5-O-glucosyldihydroflavones from the leaves of Helicia cochinchinensis.
AB  - From the leaves of Helicia cochinchinensis, collected on Okinawa Island, seven
      phenolic glucosides and two terpenic glucosides were isolated. Five of the
      phenolic glucosides were previously known, being identified with p-coumaric and
      ferulic acids glucosyl esters, rhodioloside, helicidiol, and naringenin 5-O-beta
      D-glucopyranoside. The structures of two other phenolic glucosides, named
      heliciosides A and B, were elucidated to be 5-O-beta-D-glucosides of 3
      hydroxyflavanone, namely aromadendrin and taxifolin, by means of spectroscopic
      analyses. The two terpenic glucosides were identified with ampelopsisionoside and
      icariside C1.

PMID- 16973193
TI  - Hyperforin.
AB  - Hyperforin is a polyprenylated acylphloroglucinol derivative from Hypericum
      perforatum (St. John's wort). It exhibits antidepressant activity by a novel
      mechanism of action, antibiotic activity against gram-positive bacteria, and
      antitumoral activity in vivo. However, it also produces drug-drug interactions by
      activation of the pregnan X receptor. No total synthesis has been described. Some
      natural and semisynthetic analogues are available to study structure-activity
      relationships. Enzymatically, the skeleton of hyperforin is formed by
      isobutyrophenone synthase from isobutyryl-CoA and three molecules of malonyl-CoA.
      The first prenylation step is catalyzed by a soluble and ion-dependent
      dimethylallyltransferase. Hyperforin mainly accumulates in pistils and fruits
      where it probably serves as defensive compound.

PMID- 16973195
TI  - The limits of law in the protection of public health and the role of public
      health ethics.

PMID- 16973197
TI  - Taenia saginata: a rare cause of bowel obstruction.
AB  - Taenia saginata infection is caused by the bovine tapeworm and can be the cause
      of emergency surgical conditions. We report one case of small bowel obstruction
      leading to necrosis and another case of large bowel obstruction and volvulus due
      to an impacted tapeworm. The diagnosis of these rare circumstances is usually
      made intraoperatively.

PMID- 16973198
TI  - Microbial transformation of androst-4-ene-3,17-dione by Beauveria bassiana.
AB  - The microbial transformation of androst-4-ene-3,17-dione (I) by the fungus
      Beauveria bassiana CCTCC AF206001 has been investigated using pH 6.0 and 7.0
      media. Two hydroxylated metabolites were obtained with the pH 6.0 medium. The
      major product was 11alpha-hydroxyandrost-4-ene-3,17-dione (II) whereas the minor
      product was 6beta,11alpha-dihydroxyandrost-4-ene-3,17-dione (III). On the other
      hand, four hydroxylated and/or reduced metabolites were obtained with the pH 7.0
      medium. The major product was 11alpha,17beta-dihydroxyandrost-ene-3-one (V) and
      the minor products were 17beta-hydroxyandrost-ene-3-one (IV),
      6beta,11alpha,17beta-trihydroxyandrost-ene-3-one (VI) and 3alpha,11alpha,17beta
      trihydroxy-5alpha-androstane (VII). The products were purified by chromatographic
      methods, and were identified on the basis of spectroscopic methods. This fungus
      strain is clearly an efficient biocatalyst for 11alpha-hydroxylation and
      reduction of the 17-carbonyl group.

PMID- 16973199
TI  - Superficial cell differentiation during embryonic and postnatal development of
      mouse urothelium.
AB  - After drastic urothelial destruction around birth and around postnatal day 6,
      mouse urothelial renewal starts each time de novo. The differentiation of
      superficial cells during urothelial restoration was followed for the first time
      from embryonic day 15 to postnatal day 6 by the detection of differentiation
      markers: cytokeratins, uroplakins and apical membrane specialization. The
      differentiation markers of short-lived superficial cells were studied before and
      after urothelial destruction. Three distinctive types of superficial cells,
      typical for certain developmental period, were characterised: cells at low
      differentiation stage with microvilli and cilia, expressing CK7 and CK18,
      detected on embryonic day 15; cells at advanced differentiation stage with star
      like arrangement of prominent membrane ridges, expressing CK7 and CK20, present
      between the two urothelial destruction events; highly differentiated cells with
      typically jagged apical surface, expressing CK7 and CK20, found twice during
      development. This cell type appears for the first time on embryonic day 18 as the
      terminal stage of embryonic differentiation. It was found again on postnatal day
      6 as an initial stage of differentiation, leading toward terminally
      differentiated cells of the adult urothelium. Our work proves that apical
      membrane specialization is the most valuable differentiation marker of
      superficial cells.

PMID- 16973200
TI  - Species selective resistance of cardiac muscle voltage gated sodium channels:
      characterization of brevetoxin and ciguatoxin binding sites in rats and fish.
AB  - Brevetoxins (PbTxs) and ciguatoxins (CTXs) are two suites of dinoflagellate
      derived marine polyether neurotoxins that target the voltage gated sodium channel
      (VGSC). PbTxs are commonly responsible for massive fish kills and unusual
      mortalities in marine mammals. CTXs, more often noted for human intoxication, are
      suspected causes of fish and marine mammal intoxication, although this has never
      been reported in the field. VGSCs, present in the membrane of all excitable cells
      including those found in skeletal muscle, nervous and heart tissues, are found as
      isoforms with differential expression within species and tissues. To investigate
      the tissue and species susceptibility to these biotoxins, we determined the
      relative affinity of PbTx-2 and -3 and P-CTX-1 to native VGSCs in the brain,
      heart, and skeletal muscle of rat and the marine teleost fish Centropristis
      striata by competitive binding in the presence of [(3)H]PbTx-3. No differences
      between rat and fish were observed in the binding of PbTxs and CTX to either
      brain or skeletal muscle. However, [(3)H]PbTx-3 showed substantial lower affinity
      to rat heart tissue while in the fish it bound with the same affinity to heart
      than to brain or skeletal muscle. These new insights into PbTxs and CTXs binding
      in fish and mammalian excitable tissues indicate a species related resistance of
      heart VGSC in the rat; yet, with comparable sensitivity between the species for
      brain and skeletal muscle.

PMID- 16973201
TI  - Caspase-independent apoptosis induced in rat liver cells by plancitoxin I, the
      major lethal factor from the crown-of-thorns starfish Acanthaster planci venom.
AB  - Plancitoxin I, the major lethal factor from the crown-of-thorns starfish
      Acanthaster planci venom, is quite unique not only in exhibiting potent
      hepatotoxicity but also in sharing high sequence homology with mammalian
      deoxyribonulease II. In this study, morphological and biochemical changes in rat
      liver epithelial cells (TRL 1215 cells) treated with the toxin were examined to
      understand the mechanism by which plancitoxin I displays hepatotoxicity.
      AlamarBlue assay established that plancitoxin I is cytolethal to TRL 1215 cells.
      This cytolethalithy was ascribable to apoptotic cell death. Nuclear fragmentation
      evidenced by either Diff-Quick or Hoechst 33258 staining, DNA fragmentation by
      TUNEL assay and electrophoretic analysis on agarose gel and phosphatidylserine
      externalization by flow cytometric analysis of annexin V-FITC stained cells were
      all characteristics of apoptosis. The observed apoptosis was shown to be
      independent of the caspase 3 cascade that is generally accepted as the effector
      of the apoptotic process. Very interestingly, experiments using FITC-labeled
      plancitoxin I proved that the toxin can enter the nucleus of TRL 1215 cells. Our
      results suggested that plancitoxin I induces apoptosis of TRL 1215 cells through
      the following procedure: binding to a specific receptor in the cytoplasmic
      membrane, entering the cell, entering the nucleus and degrading DNA.

PMID- 16973202
TI  - Effect of soil amendments on sorption and mobility of metribuzin in soils.
AB  - Metribuzin (4-amino-6-tert-butyl-4,5-dihydro-3-methylthio-1,2,4-triazin-5-one),
      is weakly sorbed to soil therefore, leaches easily to lower soil profiles. Soil
      amendments play a significant role in the management of leaching losses of
      pesticides. Therefore, present study reports the effect of organic manure and fly
      ash amendments on metribuzin downward mobility in sandy loam soil columns.
      Application of animal manure [T-1(OM) and T-2(OM)] and fly ash [T-1(FA) and T
      2(FA)] at 2.5% and 5.0% levels increased the metribuzin retention in the soil.
      Freundlich constant [K(f)(1/n)] values of metribuzin for treatments T-1(OM) and T
      2(OM) were 0.70 and 1.11, respectively, which were significantly higher than the
      value (0.27) in natural soil (T-0). The respective values for treatments T-1(FA)
      and T-2(FA) were 1.80 and 4.61. Downward mobility of metribuzin was studied in
      packed soil columns [300 mm (l)x59 mm (i.d.)]. Both the amendments significantly
      reduced the downward mobility of metribuzin and affected breakthrough time and
      maximum concentration of metribuzin in the leachate. Leaching losses of
      metribuzin were decreased from 97% in natural soil (T-0) column to 64% [T-1(OM)]
      and 42% [T-2(OM)] for animal manure-amended columns and 26% [T-1(FA)] to 100% [T
      2(FA)] for fly ash-amended columns, as metribuzin did not leach out of 5% fly ash
      amended column. Study indicates that both animal manure and fly ash were quite
      effective in reducing the downward mobility of metribuzin in packed soil columns
      of a sandy loam soil.

PMID- 16973203
TI  - Mechanism of decolorization and degradation of CI Direct Red 23 by ozonation
      combined with sonolysis.
AB  - The decolorization and degradation of CI Direct Red 23, which is suspected to be
      carcinogenic, were investigated using ozonation combined with sonolysis. The
      results showed that the combination of ozonation and sonolysis was a highly
      effective way to remove color from waste water. The operational parameters,
      namely concentration of the dye, pH, ozone dose and ultrasonic density, were
      investigated during the process. The decolorization of the dye followed pseudo
      first-order kinetics. Increasing the initial concentration of Direct Red 23 led
      to a decreasing rate constant. The optimum pH for the reaction was 8.0, and both
      lower and higher pH decreased the removal rate. The effect of the ozone dose on
      the dye decolorization was much greater than that of the sonolysis density.
      Intermediates such as naphthalene-2-sulfonic acid, 1-naphthol, urea and acetamide
      were detected by gas chromatography coupled with mass spectrometry in the absence
      of pH buffer, while nitrate and sulfate ions and formic, acetic and oxalic acids
      were detected by ion chromatography. A tentative degradation pathway was proposed
      without any further quantitative analyses. During the degradation, all nitrogen
      atoms and phenyl groups of Direct Red 23 were degraded into urea, nitrate ion,
      nitrogen and formic, acetic and oxalic acids, etc.

PMID- 16973204
TI  - Arsenic biogeochemistry and human health risk assessment in organo-arsenical
      pesticide-applied acidic and alkaline soils: an incubation study.
AB  - Organo-arsenical compounds are considered non-carcinogenic, and hence, are still
      allowed by the regulatory agencies for use in agriculture as pesticides. Due to
      rapid encroachment of suburban areas into former agricultural lands, the
      potential for human exposure to soil-arsenic has increased tremendously in recent
      years. However, insufficient data is available on the stability of organo
      arsenicals in soils; as to whether they remain in an organic form, or are
      converted over time to potentially carcinogenic inorganic forms. A static
      incubation study was conducted to estimate soil speciation and in-vitro
      bioavailability (i.e., bioaccessibility) of arsenic as a function of soil
      properties. Two chemically variant soil types were chosen, based on their
      potential differences with respect to arsenic reactivity: an acid sand with
      minimal arsenic retention capacity and an alkaline clay loam with relatively high
      concentrations of Fe/Al and Ca/Mg. The soils were amended with dimethylarsenic
      acid (DMA) at three rates, 45, 225 and 450 mg/kg, and incubated for 1 year. A
      sequential extraction scheme was employed to identify the geochemical forms of
      arsenic in soils, which were correlated with the in-vitro bioavailable fractions
      of arsenic. Human health risk calculated in terms of excess cancer risk (ECR)
      showed that risk assessment based on bioaccessible arsenic concentrations instead
      of the traditional total soil arsenic is a more realistic approach. Results
      showed that soil properties (such as pH, Fe/Al content and soil texture) of the
      two soils dictated the geochemical speciation, and hence, bioaccessibility of
      arsenic from DMA, indicating that the use of organic arsenicals as pesticides in
      mineral soils may not be a safe practice from a human health risk perspective.

PMID- 16973205
TI  - Influence of bacteria on lanthanide and actinide transfer from specific soil
      components (humus, soil minerals and vitrified municipal solid waste incinerator
      bottom ash) to corn plants: Sr-Nd isotope evidence.
AB  - Experiments have been performed to test the stability of vitrified municipal
      solid waste (MSW) incinerator bottom ash under the presence of bacteria
      (Pseudomonas aeruginosa) and plants (corn). The substratum used for the plant
      growth was a humus-rich soil mixed with vitrified waste. For the first time,
      information on the stability of waste glasses in the presence of bacteria and
      plants is given. Results show that inoculated plant samples contained always
      about two times higher lanthanide and actinide element concentrations. Bacteria
      support the element transfer since plants growing in inoculated environment
      developed a smaller root system but have higher trace element concentrations.
      Compared with the substratum, plants are light rare earth element (LREE)
      enriched. The vitrified bottom ash has to some extent been corroded by bacteria
      and plant activities as indicated by the presence of Nd (REE) and Sr from the
      vitrified waste in the plants. (87)Sr/(86)Sr and (143)Nd/(144)Nd isotope ratios
      of plants and soil components allow the identification of the corroded soil
      components and confirm that bacteria accelerate the assimilation of elements from
      the vitrified bottom ash. These findings are of importance for landfill disposal
      scenarios, and similar experiments should be performed in order to better
      constrain the processes of microbially mediated alteration of the MSW glasses in
      the biosphere.

PMID- 16973206
TI  - Roles of LAMP-1 and LAMP-2 in lysosome biogenesis and autophagy.
AB  - The lysosomal membrane proteins LAMP-1 and LAMP-2 are estimated to contribute to
      about 50% of all proteins of the lysosome membrane. Surprisingly, mice deficient
      in either LAMP-1 or LAMP-2 are viable and fertile. However, mice deficient in
      both LAMP-1 and LAMP-2 have an embryonic lethal phenotype. These results show
      that these two major lysosomal membrane proteins share common functions in vivo.
      However, LAMP-2 seems to have more specific functions since LAMP-2 single
      deficiency has more severe consequences than LAMP-1 single deficiency. Mutations
      in LAMP-2 gene cause a lysosomal glycogen storage disease, Danon disease, in
      humans. LAMP-2 deficient mice replicate the symptoms found in Danon patients
      including accumulation of autophagic vacuoles in heart and skeletal muscle. In
      embryonic fibroblasts, mutual disruption of both LAMPs is associated with an
      increased accumulation of autophagic vacuoles and unesterified cholesterol, while
      protein degradation rates are not affected. These results clearly show that the
      LAMP proteins fulfil functions far beyond the initially suggested roles in
      maintaining the structural integrity of the lysosomal compartment.

PMID- 16973207
TI  - Role of autophagy in the clearance of mutant huntingtin: a step towards therapy?
AB  - Macroautophagy (henceforth referred to simply as autophagy) is a bulk degradation
      process involved in the clearance of long-lived proteins, protein complexes and
      organelles. A portion of the cytosol, with its contents to be degraded, is
      enclosed by double-membrane structures called autophagosomes/autophagic vacuoles,
      which ultimately fuse with lysosomes where their contents are degraded. In this
      review, we will describe how induction of autophagy is protective against toxic
      intracytosolic aggregate-prone proteins that cause a range of neurodegenerative
      diseases. Autophagy is a key clearance pathway involved in the removal of such
      proteins, including mutant huntingtin (that causes Huntington's disease), mutant
      ataxin-3 (that causes spinocerebellar ataxia type 3), forms of tau that cause
      tauopathies, and forms of alpha-synuclein that cause familial Parkinson's
      disease. Induction of autophagy enhances the clearance of both soluble and
      aggregated forms of such proteins, and protects against toxicity of a range of
      these mutations in cell and animal models. Interestingly, the aggregates formed
      by mutant huntingtin sequester and inactivate the mammalian target of rapamycin
      (mTOR), a key negative regulator of autophagy. This results in induction of
      autophagy in cells with these aggregates.

PMID- 16973208
TI  - Mitochondrial damage and intralysosomal degradation in cellular aging.
AB  - Normal mitochondrial respiration is associated with a continuous production of
      superoxide and hydrogen peroxide, inevitably resulting in minor macromolecular
      damage. Damaged cellular components are not completely turned over by autophagy
      and other cellular repair systems, leading to a progressive age-related
      accumulation of biological "garbage" material, such as defective mitochondria,
      cytoplasmic protein aggregates and an intralysosomal undegradable material,
      lipofuscin. These changes primarily affect neurons, cardiac myocytes and other
      long-lived postmitotic cells that neither dilute this "garbage" by mitotic
      activity, nor are replaced by newly differentiated cells. Defective mitochondria
      are insufficient in ATP production and often generate increased amounts of
      reactive oxygen species, further enhancing oxidative stress. Lipofuscin-loaded
      lysosomes, in turn, poorly turn over mitochondria that gradually leads to the
      overload of long-lived postmitotic cells with "garbage" material, decreased
      adaptability and eventual cell death.

PMID- 16973209
TI  - The involvement of macroautophagy in aging and anti-aging interventions.
AB  - Macroautophagy is a process that sequesters and degrades organelles and
      macromolecular constituents of cytoplasm for cellular restructuring and repair,
      and as a source of nutrients for metabolic use in early starvation. Extensive
      evidence has been reported that macroautophagy process declines with increasing
      age. This impairment, probably due to ad libitum feeding, may cause accumulation
      of altered structures leading to the age-related decline in cell functions. It
      has been suggested that caloric restriction (CR) and disruption of insulin-like
      signals contrast the process of aging by prolonged stimulation of macroautophagy.
      According to this hypothesis, it is shown that life-long weekly administration of
      an anti-lipolytic drug decreases glucose and insulin levels, stimulates autophagy
      and intensifies anti-aging effects of submaximal CR.

PMID- 16973210
TI  - Autophagy in organelle homeostasis: peroxisome turnover.
AB  - When cells are confronted with an insufficient supply of nutrients in their
      extracellular fluid, they may begin to cannibalize some of their internal
      proteins as well as whole organelles for reuse in the synthesis of new
      components. This process is termed autophagy and it involves the formation of a
      double-membrane structure within the cell, which encloses the material to be
      degraded into a vesicle called an autophagosome. The autophagosome subsequently
      fuses with a lysosome/vacuole whose hydrolytic enzymes degrade the sequestered
      organelle. Degradation of peroxisomes is a specific type of autophagy, which
      occurs in a selective manner and has been mostly studied in yeast. Recently, it
      was reported that a similar selective process of autophagy occurs in mammalian
      cells with proliferated peroxisomes. Here we discuss characteristics of the
      autophagy of peroxisomes in mammalian cells and present a comprehensive model of
      their likely mechanism of degradation on the basis of known and common elements
      from other systems.

PMID- 16973211
TI  - Autophagy: a cell repair mechanism that retards ageing and age-associated
      diseases and can be intensified pharmacologically.
AB  - The process of ageing denotes a post-maturational deterioration of cells and
      organisms with the passage of time, an increased vulnerability to challenges and
      prevalence of age-associated diseases, and a decreased ability to survive. Causes
      may be found in an enhanced production of reactive oxygen species (ROS) and
      oxidative damage and not completed housekeeping, with an accumulation of altered
      ROS-hypergenerating organelles in older cells. It has been shown that autophagy
      is the only tier of defence against the accumulation of effete mitochondria and
      peroxisomes; that functioning of autophagy declines with increasing age and
      determinates cell and individual lifespan; that autophagy can be intensified by
      drugs; and that the pharmacological intensification of autophagy may be a big
      step towards retardation of ageing and prevention and therapy of age-associated
      diseases including neurodegeneration.

PMID- 16973212
TI  - Signalling and autophagy regulation in health, aging and disease.
AB  - It has become clear in recent years that autophagy not only serves to produce
      amino acids for ongoing protein synthesis and to produce substrates for energy
      production when cells become starved but autophagy is also able to eliminate
      defective cell structures and for this reason the process may be implicated in
      several diseased states. Autophagy is controlled by complex signalling pathways,
      including that used by insulin. In these pathways, phosphatidylinositol 3-kinases
      and the protein kinase mTOR play important roles.

PMID- 16973213
TI  - Stem cells and adipose tissue engineering.
AB  - A large proportion of the plastic and reconstructive surgical procedures
      performed each year are to repair soft tissue defects that result from traumatic
      injury, tumor resection, and congenital defects. These defects typically result
      from the loss of a large volume of adipose tissue. To date, no ideal filler
      material which is successful in all cases has been developed. Additionally, the
      success of using autologous fat tissue grafts to repair soft tissue defects has
      been limited. Researchers are thus investigating strategies to engineer volumes
      of adipose tissue that may be used in these cases. A necessary component for
      engineering a viable tissue construct is an appropriate cell source. Attempts to
      engineer adipose tissue have involved the use of preadipocytes and adipocytes as
      the base cell source. Increased interest surrounding the research and development
      of stem cells as a source of cells for tissue engineering has, however, led to a
      new path of investigation for developing adipose tissue-engineering strategies.
      This manuscript serves as a review of the current state of adipose tissue
      engineering methods and describes the shift toward tissue-engineering strategies
      using stem cells.

PMID- 16973214
TI  - Inositol-1,4,5-triphosphate receptors mediate activity-induced synaptic Ca2+
      signals in muscle fibers and Ca2+ overload in slow-channel syndrome.
AB  - Strict control of calcium entry through excitatory synaptic receptors is
      important for shaping synaptic responses, gene expression, and cell survival.
      Disruption of this control may lead to pathological accumulation of Ca2+. The
      slow-channel congenital myasthenic syndrome (SCS), due to mutations in muscle
      acetylcholine receptor (AChR), perturbs the kinetics of synaptic currents,
      leading to post-synaptic Ca2+ accumulation. To understand the regulation of
      calcium signaling at the neuromuscular junction (NMJ) and the etiology of Ca2+
      overload in SCS we studied the role of sarcoplasmic Ca2+ stores in SCS. Using
      fura-2 loaded dissociated fibers activated with acetylcholine puffs, we confirmed
      that Ca2+ accumulates around wild type NMJ and discovered that Ca2+ accumulates
      significantly faster around the NMJ of SCS transgenic dissociated muscle fibers.
      Additionally, we determined that this process is dependant on the activation,
      altered kinetics, and movement of Ca2+ ions through the AChR, although,
      surprisingly, depletion of intracellular stores also prevents the accumulation of
      this cation around the NMJ. Finally, we concluded that the sarcoplasmic reticulum
      is the main source of Ca2+ and that inositol-1,4,5-triphosphate receptors (IP3R),
      and to a lesser degree L-type voltage gated Ca2+ channels, are responsible for
      the efflux of this cation from intracellular stores. These results suggest that a
      signaling system mediated by the activation of AChR, Ca2+, and IP3R is
      responsible for localized Ca2+ signals observed in muscle fibers and the Ca2+
      overload observed in SCS.

PMID- 16973215
TI  - Neonatal intrahippocampal gp120 injection: an examination early in development.
AB  - The presence of human immunodeficiency virus type 1 (HIV-1) in the brain is
      believed to be responsible for mediating the pathogenesis of neurological
      abnormalities through the viral toxins gp120 and Tat. Numerous studies indicate
      neurotoxic effects of the HIV-1-protein Tat, with demonstrated neurobehavioral
      and cognitive alterations. However, less clear is the neurotoxic effect of gp120
      on neurobehavior. This study was designed to characterize the potential deficits
      in sensory-motor and preattentive functions, following intrahippocampal
      administration of gp120. Using a randomized-block design, male and female pups of
      eight Sprague-Dawley litters were injected bilaterally with either vehicle (VEH)
      (1 microl volume) or one of the three gp120 doses (1.29, 12.9, or 129 ng/microl)
      at postnatal day (P)1. Sensory-motor functions were assessed at P3, as measured
      by the righting reflex and at P8, as measured by negative geotaxis. At P24
      animals were tested on preattentive processes, as indexed by sensorimotor gating.
      Sensorimotor gating was measured by prepulse inhibition (PPI) of the auditory
      startle response (ASR) (ISIs of 0, 8, 40, 80, 120, and 4000 ms, six trial blocks,
      Latin-square design). Results indicated gp120-induced neurotoxicity on the
      righting reflex but not negative geotaxis. For sensorimotor gating, the PPI test
      demonstrated a reduced inhibition response on peak ASR latency as the dose of
      gp120 increased. No effect was noted for response inhibition on peak ASR
      amplitude. These data suggest that intrahippocampal injection of gp120 (0, 1.29,
      12.9, or 129 ng/microl) had transient neurotoxic effects on sensory-motor
      function and limited effects on preattentive processes early in development.

PMID- 16973216
TI  - Effects of AraC treatment on motor coordination and cerebellar cytoarchitecture
      in the adult rat. A possible protective role of NAC.
AB  - Intact cerebellum cytoarchitecture and cellular communication are indispensable
      for successful motor coordination and certain forms of memory. Cytosine
      arabinoside (AraC), often used as an anti-neoplastic agent in humans, can have
      cerebellum-targeting adverse effects. In order to characterize the nature of AraC
      induced cerebellar lesions in an adult rodent model, we have administered AraC
      (400 mg/kg b.w., i.p.) in adult male Wistar rats for 5 days. The animals' walking
      pattern, motor coordination, locomotion, spatial navigation and cognition were
      evaluated, along with neurofilament- and calbindin-like distribution in the
      cerebellum. AraC-treated rats demonstrated a disturbed walking pattern and a
      reduced ability of motor learning and coordination, indicative of a mild
      cerebellar deficit. Although the general locomotion and spatial cognition of AraC
      treated rats was not significantly altered, their navigation into the water, in
      terms of swimming velocity, was irregular, compared to vehicle-treated animals.
      Neurofilament-like immunostaining was reduced in the molecular cerebellar layer,
      while calbindin D 28 kDa levels were increased in Purkinje neurons, following
      AraC treatment. Administration of the antioxidant N-acetylcysteine (NAC) (200
      mg/kg b.w., p.o.), for 14 days (prior to and during AraC treatment) largely
      prevented the AraC-induced behavioral deficits. Our in vivo model of
      neurotoxicity provides data on the AraC-induced behavioral and cellular
      alterations concerning the adult rat cerebellum. Furthermore, it provides
      evidence of a possible neuroprophylactic role of the antioxidant N-acetylcysteine
      in this model of chemotherapy-induced toxicity.

PMID- 16973217
TI  - A novel technique to perform direct intraganglionar injections in rats.
AB  - The present work describes a simple method for direct drug administration into
      the dorsal root ganglion (DRG) in anesthetized rats. This technique does not
      involve surgery, is easy to learn and allows behavioral testing within minutes
      after the injection. Based on landmarks that target the L5 DRG, an orifice was
      created with a guide needle through which a specially designed needle was
      inserted for solution injection. Its introduction into the ganglia was ensured by
      the triggering of an ipsilateral hindpaw reflex. The precision of the technique
      was checked by injections of the biological dye Pontamine Sky Blue (PSB) or C14
      labeled arginine. There was no leakage of the dye to the surrounding tissues
      after a single 4 microl or three successive 2.5 microl injections (at 30-min
      intervals). Moreover, identical effects were observed with prostaglandin E2
      (PGE2), morphine or glibenclamide injected intraplantarly or in the DRG, thus
      confirming the precision of the method and suggesting that the ganglion cells and
      peripheral nociceptors may display similar receptor population.

PMID- 16973218
TI  - Interaction dynamics of neuronal oscillations analysed using wavelet transforms.
AB  - This paper describes the use of a computational tool based on the Morlet wavelet
      transform to investigate the interaction dynamics between oscillations generated
      by two anatomically distinct neuronal populations. The tool uses cross wavelet
      transform, coherence, bi-spectrum/bi-coherence and phase synchronization. Using
      specimen data recorded from the hippocampus of a rat with experimentally induced
      focal epilepsy, linear and non-linear correlations between neuronal oscillations
      in the CA1 and CA3 regions have been computed. The results of this real case
      study show that the computational tool can successfully analyse and quantify the
      temporal interactions between neuronal oscillators and could be employed to
      investigate the mechanisms underlying epilepsy.

PMID- 16973219
TI  - Bipolar II and anxious reactive "comorbidity": toward better phenotypic
      characterization suitable for genotyping.
AB  - OBJECTIVE: In DSM-IV, bipolar II (BP-II) disorder is defined by depression and
      hypomania. There is little appreciation of affective instability, often
      associated with anxiety-particularly panic disorder and agoraphobia (PDA)
      comorbidity. This association has genetic-familial implications, which we believe
      must be incorporated in refining the BP-II phenotype suitable for genotyping
      purposes. METHOD: We examined in a semi-structured format 107 consecutive
      patients who met DSM-IV criteria for major depressive episode with atypical
      features and separated them into two subgroups according to the co-occurring
      criteria for PDA. They were further evaluated on the basis of the Atypical
      Depression Diagnostic Scale (ADDS), the Hopkins Symptoms Check-list (HSCL 90),
      and the Hamilton Rating Scale for Depression (HRSD), coupled with its modified
      form for reverse vegetative features, as well as Axis I and II comorbidity and
      temperamental dispositions, particularly cyclothymic instability. RESULTS: Fifty
      (46.7%) of our patients met the DSM-IV criteria for PDA. In terms of significant
      results, PDA+ was more frequently female, had higher number of hypomanic
      episodes, and stressors; they were also more often BP-II, and cyclothymic.
      Ratings of reactivity, somatization, OCD and phobic anxiety too were
      significantly higher among the PDA+. In related analyses, most AD (75.7%) met
      criteria for BP-II; the BP-II subgroup was characterized by PDA, as well as
      borderline personality features and cyclothymic and hyperthymic temperaments.
      LIMITATIONS: Correlational clinical study in which clinicians could not be kept
      entirely blind to the variables under investigation. CONCLUSIONS: In line with
      the description by the French psychiatrist Pierre Kahn a century earlier,
      cyclothymic reactivity and neurotic features (i.e., atypicality and panic
      attacks) appear relevant to the definition of what today we consider BP-II
      disorder. These data, which are in line with current familial-genetic models of
      this disorder, suggest that the DSM-IV characterization of BP-II must be enriched
      by greater emphasis on temperamentally based mood and anxious reactivity. Such
      phenotypic characterization is likely to assist in better genotyping. Previous
      work by us further suggests the relevance of bulimic and addictive tendencies, as
      well as "borderline personality" diagnosis in the proband and/or the family. We
      submit that these conditions, rather than being "comorbid," constitute, along
      with BP-II, a spectrum of overlapping underlying genetic diatheses.

PMID- 16973220
TI  - Relationship between obsessive-compulsive symptoms and smoking habits amongst
      schizophrenic patients.
AB  - The rate of smoking is especially high among patients with schizophrenia (SCH)
      and schizoaffective disorder (SCHAFF). Patients with obsessive-compulsive
      disorder (OCD) smoke less than the general population. OCD symptoms are more
      frequent among patients with SCH or SCHAFF than in the general population, but it
      is still unclear whether schizophrenia patients with OC symptoms suffer from SCH
      and comorbid OCD, or whether they represent a unique subgroup of SCH with
      presenting OC symptoms. In our study we hypothetised that the current smoking
      rate of schizophrenia patients with OC symptoms is lower than in schizophrenia
      patients without OC symptoms. We assessed OC symptoms with the Yale-Brown
      Obsessive Compulsive Scale (Y-BOCS), general state with the Brief Psychiatric
      Rating Scale (BPRS) and smoking habits with a questionnaire among 66 patients
      with SCH or SCHAFF. We formed two groups by dividing patients according to their
      Y-BOCS score. Group I consisted of patients with Y-BOCS scores under 16, while
      group II consisted of patients with Y-BOCS scores above 16, and we compared the
      current smoking rates of the two groups. We found that the rates did not differ
      significantly, so we came to the conclusion that OC symptoms are not in a tight
      relationship with smoking habits among patients with SCH/SCHAFF.

PMID- 16973221
TI  - Lactoferrin expression in the horse endometrium: relevance in persisting mating
      induced endometritis.
AB  - Lactoferrin (LF) is an estrogen-regulated glycoprotein with well-described
      antibacterial and immunomodulatory properties. The present study is the first
      report on LF expression in horse endometrial specimens. Mares chosen for the
      study were either resistant or susceptible for persisting mating-induced
      endometritis (PMIE) during the natural ovulatory cycle and in early pregnancy.
      Our investigations included immunostaining for LF protein and CD18, a leukocyte
      marker, as neutrophils are a possible source for LF in the endometrium.
      Quantification of LF mRNA was performed by use of real-time RT-PCR. This study
      demonstrated that LF protein in equine endometrium was expressed in glandular and
      luminal epithelium and in neutrophils. Similar to other mammalian species, the
      level of endometrial LF transcription in the mare was modulated according to the
      stage of the estrus cycle and was 5500-fold higher during estrus compared with
      diestrus and early pregnancy. The endometria from mares susceptible for PMIE and
      delayed uterine clearance exhibited an increased LF transcription during all
      stages of the estrus cycle that reached statistical significance in proestrus. In
      the endometria of mares susceptible for PMIE the upregulated LF mRNA expression
      was not associated with a higher number of CD18 positive leukocytes but
      correlated with the number of uterine glands. Enhanced LF transcription within
      the endometrial epithelium might therefore be a response to recurrent persisting
      inflammation following insemination in mares with delayed uterine clearance.

PMID- 16973222
TI  - Tympanometry by nurses--can allocation of tasks be optimised?
AB  - OBJECTIVE: Acute otitis media and secretory otitis media are the most common
      pediatric infectious disease with a substantial impact on especially primary
      health care. If nurses could perform and interpret tympanometries, family
      practitioners workload could be reduced. We wanted to investigate the ability of
      nurses to perform tympanometry and evaluate the amount of training required.
      METHODS: Prospective study comparing results from tympanometry with results at
      myringotomy at a University Central Hospital was conducted. Nurses at the
      Paediatric Ear, Nose, and Throat Department performed tympanometry prior to
      myringotomy. Sensitivity and specificity of tympanometries versus myringotomy
      were calculated. Nurses' opinions about tympanometry and training required were
      evaluated. RESULTS: During a 1-year period, 199 children were enrolled in the
      study and 392 tympanograms were analyzed. Sensitivity of tympanograms to detect
      middle-ear fluid was 0.54, and specificity 0.82. Secretion occurred in 22.5% of
      children with type A curves and 45.3% of those with type C curves. Nurses
      evaluated their training in tympanometry as adequate. CONSCLUSIONS: A single
      training session in tympanometry is inadequate to qualify nurses to perform
      tympanometry independently. Thorough research and testing to evaluate the quality
      of such training is required to produce reliable tympanograms.

PMID- 16973223
TI  - Outcomes of reduced postoperative stay following outpatient pediatric
      tonsillectomy.
AB  - OBJECTIVE: To assess outcomes of reduced postoperative recovery room observation
      times and associated complication rates following outpatient pediatric
      adenotonsillectomy at a tertiary care medical center outpatient facility over a
      7.5-year period. STUDY DESIGN: Retrospective chart review. METHODS: Charts from
      all outpatient pediatric adenotonsillectomies performed by one surgeon from
      January 1998 through June 2005 at a tertiary care center were reviewed. RESULTS:
      Seven hundred and ninety seven (797) charts had sufficient documentation to be
      included in this study. Mean patient age was 6.8 years (median 5.5 years, range 2
      21 years). There were 53 patients under 3 years old (6.64%), 655 patients age 3
      12 years (82.18%), and 89 patients age 12-21 years (11.17%). Mean postoperative
      recovery room observation time prior to discharge was 1.47 h (median 1.33 h,
      range 0.45-7.25 h). Primary (<24 h postoperative) complication rate was 0.0075%,
      and secondary (>24 h postoperative) complication rate was 0.0063%. There were no
      significant differences in duration of postoperative recovery room observation or
      postoperative complications between the three age groups (p=0.10). CONCLUSIONS:
      Very brief postoperative observation periods following outpatient pediatric
      adenotonsillectomy may be considered safe, without added risk nor increased short
      term or long-term complications. While individual cases may merit prolonged
      postoperative observation periods, the majority of study patients had no
      postoperative complications despite shorter recovery room stays than described in
      prior reports. These data support safety and efficacy of reduced postoperative
      stays. Our data should be considered in order to increase the efficiency and cost
      effectiveness of outpatient surgery centers where such procedures are performed.

PMID- 16973224
TI  - Metabolism of pyrene by aquatic crustacean, Daphnia magna.
AB  - The aquatic crustacean Daphnia magna is an important species for ecotoxicological
      study, and is often used as a test organism for environmental risk assessment.
      However, the mechanism of xenobiotic metabolism by this species has not been
      studied in detail. In the present study, pyrene was used as model substance to
      investigate the mechanism of xenobiotic metabolism in D. magna. The results of 24
      h exposure experiments showed that D. magna could metabolize pyrene and
      biotransform it into water-soluble metabolites. On the other hand, the metabolism
      of pyrene was significantly inhibited by SKF-525A as the cytochrome P450 (CYP)
      inhibitor. These observations indicated that oxidation by CYP participated in the
      biotransformation of pyrene by D. magna. We also identified the pyrene
      metabolites formed by D. magna by HPLC with an electrospray ionization triple
      quadrupole mass spectrometry detector (LC/ESIMS/MS) and de-conjugation by
      sulfatase, beta-glucuronidase, and beta-glucosidase. One of the metabolites was
      ionized in ESI negative mode and formed a dominant mass of m/z 297 (MS) with the
      product ion of m/z 217 (MS2). Furthermore, this metabolite formed 1-hydroxypyrene
      on treatment with sulfatase. This metabolite was considered to be a sulfate
      conjugate of oxidized pyrene (1-hydroxypyrenesulfate). Furthermore, we quantified
      the deconjugated 1-hydroxypyrene formed by the above enzyme treatment. It showed
      that 52% of the total metabolized pyrene was biotransformed into 1-hydroxypyrene
      sulfate, and more than 73% was biotransformed into oxidized pyrene conjugate.
      These results indicated that CYP and several conjugation enzymes participate in
      its biotransformation, and sulfation is important in D. magna for metabolism and
      elimination of xenobiotics.

PMID- 16973225
TI  - The role of TGF-beta1 as a determinant of foreign body reaction to alloplastic
      materials in rat fibroblast cultures: comparison of different commercially
      available polypropylene meshes for hernia repair.
AB  - BACKGROUND: Animal experiments on hernia repair demonstrated better
      biocompatibility of light-weight polypropylene meshes. However, implanted medical
      devices trigger a variety of adverse tissue responses, such as inflammation,
      fibrosis, infection and thrombosis, but the mechanisms involved in such responses
      remain largely unknown. This study aimed to determine the effect of transforming
      growth factor beta1 (TGF-beta1) on host tolerance by quantification of foreign
      body reaction in cultured fibroblasts depending on the amount and composition of
      implanted material used for hernia repair. MATERIALS AND METHODS: An NRK-49F
      fibroblast culture was incubated in the presence of 4 commercially available
      meshes approved for hernia repair. A mesh-free cell suspension served as a
      control group, in which the influence of TGF-beta1 on fibroblasts was evaluated.
      Levels of TGF-beta1 in the supernatant were dynamically measured in a time
      interval of 6 to 96 h and cell proliferation rates were assessed colorimetrically
      using MTT test. RESULTS: A dose-dependent suppression of fibroblasts
      proliferation by TGF-beta1 was observed. All meshes suppressed the secretion of
      TGF-beta1 and conversely increased significantly cell proliferation in comparison
      to the control group (p<0.01) in the first 24 to 48 h of incubation. That effect
      was more pronounced in meshes partially containing absorbable material when
      compared to samples of pure polypropylene meshes (p<0.05) and to the control
      group (p<0.001). CONCLUSION: Our experiment revealed that early biological
      reaction of connective tissue cells towards polypropylene meshes and their
      variants depended much more on the composition and type of the material than on
      its absolute amount. The assumption that material weight reduction alone might
      affect the foreign body reaction of mesh implants could not be confirmed by our
      in vitro study.

PMID- 16973226
TI  - Microbial source tracking by DNA sequence analysis of the Escherichia coli malate
      dehydrogenase gene.
AB  - Criteria for sub-typing of microbial organisms by DNA sequencing proposed by
      Olive and Bean were applied to several genes in Escherichia coli to identify
      targets for the development of microbial source tracking assays. Based on the
      aforementioned criteria, the icd (isocitrate dehydrogenase), and putP (proline
      permease) genes were excluded as potential targets due to their high rates of
      horizontal gene transfer; the rrs (16S rRNA) gene was excluded as a target due to
      the presence of multiple gene copies, with different sequences in a single
      genome. Based on the above criteria, the mdh (malate dehydrogenase) gene was
      selected as a target for development of a microbial source tracking assay. The
      mdh assay was optimized to analyze a 150 bp fragment corresponding to residues
      G191 to R240 (helices H10 and H11) of the Mdh catalytic domain. 295 fecal
      isolates (52 horse, 50 deer, 72 dog, 52 seagull and 69 human isolates) were
      sequenced and analyzed. Target DNA sequences for isolates from horse, dog plus
      deer, and seagull formed identifiable groupings. Sequences from human isolates,
      aside from a low level (ca. 15%) human specific sequence, did not group;
      nevertheless, other hosts could be distinguished from human. Positive and
      negative predictive values for two- and three-way host comparisons ranged from
      60% to 90% depending on the focus host. False positive rates were below 10%.
      Multiple E. coli isolates from individual fecal samples exhibited high levels of
      sequence homogeneity, i.e. typically only one to two mdh sequences were observed
      per up to five E. coli isolates from a single fecal sample. Among all isolates
      sequenced from fecal samples from each host, sequence homogeneity decreased in
      the following order: horse>dog>deer>human and gull. For in-library isolates,
      blind analysis of fecal isolates (n=12) from four hosts known to contain host
      specific target sequences was 100% accurate and 100% reproducible for both DNA
      sequence and host identification. For blind analysis of non-library isolates,
      18/19 isolates (94.7%) matched one or more library sequences for the
      corresponding host. Ten of eleven geographical outlier fecal isolates from
      Florida had mdh sequences that were identical to in-library sequences for the
      corresponding host from California. The mdh assay was successfully applied to
      environmental isolates from an underground telephone vault in California, with 4
      of 5 isolates matching sequences in the mdh library. 146 sequences of the 645bp
      mdh fragment from five host sources were translated into protein sequence and
      aligned. Seven unique Mdh protein sequences, which contained eight polymorphic
      sites, were identified. Six of the polymorphic sites were in the NAD+ binding
      domain and two were in the catalytic domain. All of the polymorphic sites were
      located in surface exposed regions of the protein. None of the non-silent
      mutations of the Mdh protein were in the 150bp mdh target. The advantages and
      disadvantages of the assay compared to established source tracking methods are
      discussed.

PMID- 16973227
TI  - Outcome of secondary high-grade glioma in children previously treated for a
      malignant condition: a study of the Canadian Pediatric Brain Tumour Consortium.
AB  - BACKGROUND AND PURPOSE: Reports of secondary high-grade glioma (HGG) in survivors
      of childhood cancer are scarce. The aim of this study was to review the pattern
      of diagnosis, the treatment, and outcome of secondary pediatric HGG. PATIENTS AND
      METHODS: We performed a multi-center retrospective study among the 17 paediatric
      institutions participating in the Canadian Pediatric Brain Tumour Consortium
      (CPBTC). RESULTS: We report on 18 patients (14 males, 4 females) treated in
      childhood for a primary cancer, who subsequently developed a HGG as a second
      malignancy. All patients had previously received radiation therapy +/-
      chemotherapy for either acute lymphoblastic leukaemia (n=9) or solid tumour
      (n=9). All HGG occurred within the previous radiation fields. At the last follow
      up, 17 patients have died and the median survival time is 9.75 months.
      CONCLUSION: Although aggressive treatment seems to provide sustained remissions
      in some patients, the optimal management is still to be defined. Further
      documentation of such cases is necessary in order to better understand the
      pathogenesis, the natural history and the prevention of these tumours.

PMID- 16973228
TI  - Tumor lactate content predicts for response to fractionated irradiation of human
      squamous cell carcinomas in nude mice.
AB  - BACKGROUND AND PURPOSE: The present study was performed to test the hypothesis
      that lactate accumulation correlates with the radioresistance of malignant tumors
      due to the radical scavenging capacity of lactate or metabolic intermediates of
      glycolysis, such as pyruvate. MATERIALS AND METHODS: Five human head and neck
      squamous cell carcinoma cell lines (HNSCCs) xenografted in nude mice were treated
      with a clinically relevant irradiation protocol with 30 fractions within 6 weeks.
      The radiation dose necessary to locally control 50% of the tumors (TCD50) ranged
      from 47.4 to 129.8 Gy. Concentrations of glucose, lactate, and ATP in viable
      tumor regions as potential indicators of glycolytic activity were assessed with
      structure-associated quantitative bioluminescence imaging. RESULTS: Mean lactate
      concentrations of the different tumor cell lines were in the range of 7.3-25.9
      micromol/g. TCD50 values were positively correlated with tumor lactate levels (R
      = 0.9824, p = 0.0028). CONCLUSIONS: The data obtained support the hypothesis that
      tissue lactate content correlates with radioresistance in solid human tumors.
      Furthermore, the results suggest that tumor lactate content determined non
      invasively by proton magnetic resonance spectroscopy imaging may be used to
      predict for radioresistance of malignancies in the clinic; the data also imply
      that transient inhibition of glycolysis during treatment might possibly sensitize
      tumors to irradiation.

PMID- 16973229
TI  - Contribution of the kinetics of G protein dissociation to the characteristic
      modifications of N-type calcium channel activity.
AB  - Direct G protein inhibition of N-type calcium channels is recognized by
      characteristic biophysical modifications. In this study, we quantify and simulate
      the importance of G protein dissociation on the phenotype of G protein-regulated
      whole-cell currents. Based on the observation that the voltage-dependence of the
      time constant of recovery from G protein inhibition is correlated with the
      voltage-dependence of channel opening, we depict all G protein effects by a
      simple kinetic scheme. All landmark modifications in calcium currents, except
      inhibition, can be successfully described using three simple biophysical
      parameters (extent of block, extent of recovery, and time constant of recovery).
      Modifications of these parameters by auxiliary beta subunits are at the origin of
      differences in N-type channel regulation by G proteins. The simulation data
      illustrate that channel reluctance can occur as the result of an experimental
      bias linked to the variable extent of G protein dissociation when peak currents
      are measured at various membrane potentials. To produce alterations in channel
      kinetics, the two most important parameters are the extents of initial block and
      recovery. These data emphasize the contribution of the degree and kinetics of G
      protein dissociation in the modification of N-type currents.

PMID- 16973230
TI  - Reticulo-collicular and spino-collicular projections involved in eye and eyelid
      movements during the blink reflex.
AB  - Reflex blinking provides a useful experimental tool for various functional
      studies on the peripheral and central nervous system, yet the neuronal circuitry
      underlying this reflex is not precisely known. In the present study, we
      investigated as to whether neurons in the reticular formation and rostral
      cervical spinal cord (C1) may be involved in the blink reflex in rats. To this
      end we investigated c-Fos expression in these areas following supraorbital nerve
      stimulation combined with retrograde tracing of gold conjugated horse radish
      peroxidase (Gold-HRP) from the superior colliculus. We observed many double
      labeled neurons in the parvocellular reticular nucleus, medullary reticular
      formation, and laminae IV and V of C1. Thus, these brain regions contain neurons
      that may be involved in blink reflexes as well as eye movements, because they
      both can be activated following peri-orbital stimulation and project to the
      superior colliculus. Consequently, we suggest that the medullary reticular
      formation and C1 region play a central role in the coordination of eye and eyelid
      movements during reflex blinking.

PMID- 16973231
TI  - Somatotopically arranged inputs from putamen and subthalamic nucleus to primary
      motor cortex.
AB  - Employing retrograde transsynaptic transport of rabies virus, we investigated the
      organization of basal ganglia inputs to hindlimb, proximal and distal forelimb,
      and orofacial representations of the macaque primary motor cortex (MI). Four days
      after rabies injections into these MI regions, neuronal labeling occurred in the
      striatum and the subthalamic nucleus (STN) through the cortico-basal ganglia loop
      circuits. In the striatum, two distinct sets of the labeling were observed: one
      in the dorsal putamen, and the other in the ventral striatum (ventromedial
      putamen and nucleus accumbens). The dorsal striatal labeling was somatotopically
      arranged and its distribution pattern was in good accordance with that of the
      corticostriatal inputs, such that the hindlimb, orofacial, or forelimb area was
      located in the dorsal, ventral, or intermediate zone of the putamen,
      respectively. The distribution pattern of the ventral striatal labeling was
      essentially the same in all cases. In the STN, the somatotopic arrangement of
      labeled neurons was in register with that of corticosubthalamic inputs. The
      present results suggest that the cortico-basal ganglia motor circuits involving
      the dorsal putamen and the STN may constitute separate closed loops based on the
      somatotopy, while the ventral striatum provides common multisynaptic projections
      to all body-part representations in the MI.

PMID- 16973232
TI  - Cryptosporidium and Giardia in commercial and non-commercial oysters (Crassostrea
      gigas) and water from the Oosterschelde, The Netherlands.
AB  - The intestinal parasites Cryptosporidium and Giardia cause gastro-enteritis in
      humans and can be transmitted via contaminated water. Oysters are filter feeders
      that have been demonstrated to accumulate pathogens such as Salmonella, Vibrio,
      norovirus and Cryptosporidium from contaminated water and cause foodborne
      infections. Oysters are economically important shellfish that are generally
      consumed raw. Commercial and non-commercial oysters (Crassostrea gigas) and
      oyster culture water from the Oosterschelde, The Netherlands, were examined for
      the presence of Cryptosporidium oocysts and Giardia cysts. Nine of 133 (6.7%)
      oysters from two non-commercial harvesting sites contained Cryptosporidium,
      Giardia or both. Six of 46 (13.0%) commercial oysters harboured Cryptosporidium
      or Giardia in their intestines. Data on the viability of (oo)cysts recovered from
      Oosterschelde oysters were not obtained, however viable (oo)cysts were detected
      in surface waters that enter the Oosterschelde oyster harvesting areas. The
      detection of Cryptosporidium and Giardia in oysters destined for human
      consumption has implications for public health only when human pathogenic
      (oo)cysts that have preserved infectivity during their stay in a marine
      environment are present. Our data suggest that consumption of raw oysters from
      the Oosterschelde may occasionally lead to cases of gastro-intestinal illness.

PMID- 16973233
TI  - Levels of cystathionine gamma lyase production by Geotrichum candidum in
      synthetic media and correlation with the presence of sulphur flavours in cheese.
AB  - Geotrichum candidum is a cheese-ripening agent with the potential to produce
      sulphur flavour compounds in soft cheeses. We aimed to develop an alternative
      test for predicting the aromatic (sulphur flavours) potential of G. candidum
      strains in soft cheese. Twelve strains of G. candidum with different levels of
      demethiolase activity (determined by a chemical method) in YEL-met (yeast
      extract, lactate methionine) medium were studied. We investigated cgl
      (cystathionine gamma lyase) gene expression after culture in three media - YEL
      met, casamino acid and curd media - and then carried out sensory analysis on a
      Camembert cheese matrix. We found no correlation between demethiolase activity in
      vitro and cgl gene expression. Sensory analysis (detection of sulphur flavours)
      identified different aromatic profiles linked to cgl expression, but not to
      demethiolase activity. The RT-PCR technique described here is potentially useful
      for predicting the tendency of a given strain of G. candidum to develop sulphur
      flavours in cheese matrix. This is the first demonstration that an in vitro
      molecular approach could be used as a predictive test for evaluating the
      potential of G. candidum strains to generate sulphur compounds in situ (Camembert
      cheese matrix).

PMID- 16973234
TI  - Biodegradation kinetics of 2,4-dichlorophenol by acclimated mixed cultures.
AB  - The biodegradation kinetics of 2,4-dichlorophenol (2,4-DCP) by culture (Culture
      M) acclimated to mixture of 4-chlorophenol (4-CP) and 2,4-DCP and the culture
      (Culture 4) acclimated to 4-CP only were investigated in aerobic batch reactors.
      Also, pure strains isolated from mixed cultures were searched for their ability
      towards the biodegradation of 2,4-DCP. Culture 4 was able to completely degrade
      2,4-DCP up to 80 mg/L within 30 h and removal efficiency dropped to 21% upon
      increasing initial concentration to 108.8 mg/L. When the Culture M was used,
      complete degradation of 2,4-DCP in the range of 12.5-104.4 mg/L was attained. A
      linear relationship between time required for complete degradation and initial
      2,4-DCP concentrations was observed for both mixed cultures. It was observed that
      the Haldane equation can be used to predict specific degradation rate (SDR)
      (R(2)>0.99) as a function of initial 2,4-DCP concentrations and it adequately
      describes 2,4-DCP concentration profiles. Both of the mixed cultures settled
      well, which is important to maintain good removal efficiency for longer periods
      of time for real full-scale applications. Although the pure strains isolated from
      mixed cultures were found to have higher SDR of 2,4-DCP compared to mixed
      cultures, they did not settle well under quiescent conditions.

PMID- 16973235
TI  - Importance of bile acids for novel oral absorption system containing polyamines
      to improve intestinal absorption.
AB  - The synergetic improving effect of bile acids with spermine (SPM), a major
      polyamine, on the absorption of rebamipide, a poorly soluble and poorly
      absorbable drug (BCS Class IV), was evaluated in rats and beagle dogs. Although
      the absorption of rebamipide was improved by the addition of polyamines alone in
      normal rats, it was not improved in bile duct ligated (BDL) rats. The
      combinatorial use of sodium taurocholate (STC), a bile acid, with SPM improved
      the absorption of rebamipide even in BDL rats. In the beagle dogs, the oral
      administration of SPM alone did not enhance the absorption of rebamipide, but the
      combinatorial use of STC with SPM improved the absorption as well as in the BDL
      rats. These results indicate that bile acids are indispensable for the novel
      formulation containing SPM to improve the absorption of rebamipide after oral
      administration.

PMID- 16973236
TI  - Incorporation into a biodegradable hyaluronic acid matrix enhances in vivo
      efficacy of recombinant human interleukin 11 (rhIL11).
AB  - In order to improve the therapeutic efficacy of recombinant human interleukin 11
      (rhIL11) and to reduce its frequency of administration, the feasibility of a
      sustained release formulation consisting of hyaluronic acid (HyA) was
      investigated. rhIL11 was mixed together with an aqueous solution of HyA or HyA
      and protamine, and the mixture was lyophilized. The resulting powder was
      compressed into pellet and was subcutaneously administered in the rats. The
      plasma profile of rhIL11 was determined by ELISA. The mean residence time and
      t(max) of rhIL11 were much prolonged by administration in an HyA pellet. The
      additional incorporation of protamine into the formulation further enhanced the
      plasma duration of the protein. Separately, peripheral platelet counts were
      measured for several rhIL11-containing solution and pellets. Platelet counts much
      increased after administration of rhIL11-containing pellets, whereas the effect
      of bolus subcutaneous administration of rhIL11 solution was limited. The degree
      of platelet increase in rats treated with the pellets was comparable to that for
      rats treated with 1- or 2-day continuous infusion from an osmotic mini-pump;
      these data reflect the importance of increased plasma duration of rhIL11. These
      data indicate that use of hyaluronic acid as a polymer matrix might enhance the
      therapeutic efficacy of rhIL11.

PMID- 16973237
TI  - Overlapping genes as rare genomic markers: the phylogeny of gamma-Proteobacteria
      as a case study.
AB  - Phylogenies can be constructed in many ways, including using shared complex
      characters known as rare genomic changes (RGCs), such as insertions and deletions
      (indels), retroposon integrations and intron positions. Here, we demonstrate that
      distance-based phylogenies, which were determined by shared overlapping genes
      from 13 completely sequenced gamma-Proteobacteria genomes, are consistent with
      phylogenies based on 16S rRNAs and other robust markers. These findings suggest
      that overlapping genes could provide interesting additional insights into the
      phylogenomics of completely sequenced microbial genomes.

PMID- 16973238
TI  - Correlates of vegetable consumption among young men in the Norwegian National
      Guard.
AB  - The aim of this study was to investigate socio-environmental, personal and
      behavioural factors associated with vegetable consumption among young men in the
      military. Respondents included 578 male recruits (mean age 19.7) in the Norwegian
      National Guard (response rate 78%). Data were collected with a food diary (4-day
      record) and an attitudinal questionnaire. A model including items on personal
      factors (attitudes, preferences, self-efficacy, knowledge and perceived
      availability), socio-environmental factors (social influence, socio-economic
      status, eating habits at home) and behavioural factors (meal frequency, number of
      hot meals, snack consumption, smoking) was developed to assess correlates of the
      recruits' vegetable intake. The study showed that the recruits' consumption of
      vegetables (including potatoes) varied from 0 to 957 g/day with an average of 244
      g/day. Overall, 32% of the variance in vegetable consumption was explained by
      factors included in the model. The most important correlates were occupational
      status of the parents, frequency of vegetable consumption when living at home,
      social influence, preferences for cooked vegetables, weight beliefs, number of
      hot meals for lunch and dinner and smoking habits. In conclusion, the present
      study indicates that in addition to cognitive factors, socio-environmental and
      behavioural factors can explain the variance in vegetable intake among young men
      in the military.

PMID- 16973239
TI  - Endogenous opiates and behavior: 2005.
AB  - This paper is the 28th consecutive installment of the annual review of research
      concerning the endogenous opioid system, now spanning over a quarter-century of
      research. It summarizes papers published during 2005 that studied the behavioral
      effects of molecular, pharmacological and genetic manipulation of opioid
      peptides, opioid receptors, opioid agonists and opioid antagonists. The
      particular topics that continue to be covered include the molecular-biochemical
      effects and neurochemical localization studies of endogenous opioids and their
      receptors related to behavior (Section 2), and the roles of these opioid peptides
      and receptors in pain and analgesia (Section 3); stress and social status
      (Section 4); tolerance and dependence (Section 5); learning and memory (Section
      6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8);
      sexual activity and hormones, pregnancy, development and endocrinology (Section
      9); mental illness and mood (Section 10); seizures and neurologic disorders
      (Section 11); electrical-related activity, neurophysiology and transmitter
      release (Section 12); general activity and locomotion (Section 13);
      gastrointestinal, renal and hepatic functions (Section 14); cardiovascular
      responses (Section 15); respiration and thermoregulation (Section 16);
      immunological responses (Section 17).

PMID- 16973240
TI  - H2O2 and Src-dependent transactivation of the EGF receptor mediates the
      stimulatory effect of leptin on renal ERK and Na+, K+-ATPase.
AB  - We examined the mechanism through which leptin increases Na(+), K(+)-ATPase
      activity in the rat kidney. Leptin was infused under anaesthesia into the
      abdominal aorta proximally to the renal arteries and then Na(+), K(+)-ATPase
      activity was measured in the renal cortex and medulla. Leptin (1mug/kgmin)
      increased Na(+), K(+)-ATPase activity after 3h of infusion, which was accompanied
      by the increase in urinary H(2)O(2) excretion and phosphorylation level of
      extracellular signal regulated kinase (ERK). The effect of leptin on ERK and
      Na(+), K(+)-ATPase was abolished by catalase, specific inhibitors of epidermal
      growth factor (EGF) receptor, AG1478 and PD158780, as well as by ERK inhibitor,
      PD98059, and was mimicked by both exogenous H(2)O(2) and EGF. The effect of
      leptin was also prevented by the inhibitor of Src tyrosine kinase, PP2. Leptin
      and H(2)O(2) increased Src phosphorylation at Tyr(418). We conclude that leptin
      induced stimulation of renal Na(+), K(+)-ATPase involves H(2)O(2) generation, Src
      kinase, transactivation of the EGF receptor, and stimulation of ERK.

PMID- 16973241
TI  - Convergence of genes implicated in Alzheimer's disease on the cerebral
      cholesterol shuttle: APP, cholesterol, lipoproteins, and atherosclerosis.
AB  - Polymorphic genes associated with Alzheimer's disease (see ) delineate a clearly
      defined pathway related to cerebral and peripheral cholesterol and lipoprotein
      homoeostasis. They include all of the key components of a glia/neurone
      cholesterol shuttle including cholesterol binding lipoproteins APOA1, APOA4,
      APOC1, APOC2, APOC3, APOD, APOE and LPA, cholesterol transporters ABCA1, ABCA2,
      lipoprotein receptors LDLR, LRP1, LRP8 and VLDLR, and the cholesterol
      metabolising enzymes CYP46A1 and CH25H, whose oxysterol products activate the
      liver X receptor NR1H2 and are metabolised to esters by SOAT1. LIPA metabolises
      cholesterol esters, which are transported by the cholesteryl ester transport
      protein CETP. The transcription factor SREBF1 controls the expression of most
      enzymes of cholesterol synthesis. APP is involved in this shuttle as it
      metabolises cholesterol to 7-betahydroxycholesterol, a substrate of SOAT1 and
      HSD11B1, binds to APOE and is tethered to LRP1 via APPB1, APBB2 and APBB3 at the
      cytoplasmic domain and via LRPAP1 at the extracellular domain. APP cleavage
      products are also able to prevent cholesterol binding to APOE. BACE cleaves both
      APP and LRP1. Gamma-secretase (PSEN1, PSEN2, NCSTN) cleaves LRP1 and LRP8 as well
      as APP and their degradation products control transcription factor TFCP2, which
      regulates thymidylate synthase (TS) and GSK3B expression. GSK3B is known to
      phosphorylate the microtubule protein tau (MAPT). Dysfunction of this cascade,
      carved out by genes implicated in Alzheimer's disease, may play a major role in
      its pathology. Many other genes associated with Alzheimer's disease affect
      cholesterol or lipoprotein function and/or have also been implicated in
      atherosclerosis, a feature of Alzheimer's disease, and this duality may well
      explain the close links between vascular and cerebral pathology in Alzheimer's
      disease. The definition of many of these genes as risk factors is highly
      contested. However, when polymorphic susceptibility genes belong to the same
      signaling pathway, the risk associated with multigenic disease is better related
      to the integrated effects of multiple polymorphisms of genes within the same
      pathway than to variants in any single gene [Wu, X., Gu, J., Grossman, H.B.,
      Amos, C.I., Etzel, C., Huang, M., Zhang, Q., Millikan, R.E., Lerner, S., Dinney,
      C.P., Spitz, M.R., 2006. Bladder cancer predisposition: a multigenic approach to
      DNA-repair and cell-cycle-control genes. Am. J. Hum. Genet. 78, 464-479.]. Thus,
      the fact that Alzheimer's disease susceptibility genes converge on a clearly
      defined signaling network has important implications for genetic association
      studies.

PMID- 16973242
TI  - Mitogen activated protein kinase and protein kinase C activation mediate
      promotion of sAPPalpha secretion by deprenyl.
AB  - The beta amyloid cascade plays a crucial role in the pathogenesis of Alzheimer's
      disease (AD). Therefore, drugs that regulate amyloid precursor protein (APP)
      processing toward the nonamyloidgenic pathway may have therapeutic potential.
      Many anti-dementia drugs can regulate APP processing in addition to their
      pharmacological properties. Deprenyl is a neuroprotective agent used to treat
      some neurodegenerative diseases, including AD. In the present study, the effects
      of deprenyl on APP processing were investigated. Using SK-N-SH and PC12 cells, it
      was demonstrated that deprenyl stimulated the release of the nonamyloidogenic
      alpha-secretase form of soluble APP (sAPPalpha) in a dose-dependent manner
      without affecting cellular APP expression. The increase of sAPPalpha secretion by
      deprenyl was blocked by the mitogen activated protein (MAP) kinase inhibitor
      U0126 and PD98059, and by the protein kinase C (PKC) inhibitor GF109203X and
      staurosporine, suggesting the involvement of these signal transduction pathways.
      Deprenyl induced phosphorylation of p42/44 MAP kinase, which was abolished by
      specific inhibitors of MAP kinase and PKC. Deprenyl also phosphorylated PKC and
      its major substrate, and myristoylated alanine-rich C kinase (MARCKS) at specific
      amino acid residues. The data also indicated that 10microM deprenyl successfully
      induced two PKC isoforms involved in the pathogenesis of AD, PKCalpha and
      PKCepsilon, to translocate from the cytosolic to the membrane fraction. This
      phenomenon was substantiated by immunocytochemistry staining. These data suggest
      a novel pharmacological mechanism in which deprenyl regulates the processing of
      APP via activation of the MAP kinase and PKC pathways, and that this mechanism
      may underlie the clinical efficacy of the drug in some AD patients.

PMID- 16973243
TI  - Regulation of G proteins by human 5-HT1a receptor TM3/i2 and TM5/i3 loop
      peptides.
AB  - A bioactive synthetic 11 amino acid peptide probe (P11) was constructed according
      to the published sequence of the human 5HT1a receptor. The probe was used to
      enhance understanding of cytoplasmic loop 2/G protein coupling and activation.
      Additionally, two peptides (P8, P9) from the cytoplasmic loop 3 region were
      synthesized and studied. These probes were tested in a model system of human
      5HT1a receptor stably expressed in Chinese Hamster Ovary cells. In agonist
      inhibition studies, P11 was active in all three receptor preparations tested:
      whole cells, membrane bound, and solubilized. In analyses of the membrane bound
      receptor system, P11 demonstrated uncompetitive inhibition characteristics. When
      forskolin-stimulated cAMP levels were measured, P11 was inactive in this
      negatively coupled system. Utilizing a [35S]gamma-S-GTP incorporation assay, P11
      was unable to stimulate G protein incorporation of GTP. While P8 and P9 were also
      broadly active as non-competitive agonist inhibitors, their characteristics
      differed in the signal transduction system. P8 and P9 did not significantly
      change forskolin-stimulated cAMP levels. However, P8 increased [35S]gamma-S-GTP
      incorporation, while P9 decreased incorporation. Thus, P11, a synthetic peptide
      from the TM3/i2 region of the receptor, provides suggestive evidence that this
      receptor region is involved in G protein coupling but not activation. On the
      other hand, P8 and P9 activities suggest that the TM5/i3 region is involved in
      both coupling to and regulation of G protein activity. The current evidence from
      these cytoplasmic loop regions is discussed in the overall context of an emerging
      model for human 5HT1a receptor-G protein interactions.

PMID- 16973244
TI  - Deficiency in the ALS2 gene does not affect the motor neuron degeneration in
      SOD1(G93A) transgenic mice.
AB  - Dysfunction of the ALS2 gene has been linked to one form of juvenile onset
      autosomal recessive amyotrophic lateral sclerosis (ALS). Previous in vitro
      studies suggest that over-expression of ALS2 protects cells from mutant Cu/Zn
      superoxide dismutase (SOD1)-induced cytotoxicity. To test whether ALS2 plays a
      protective role against mutant SOD1-mediated motor neuron degeneration in vivo,
      we examined the progression of motor neuron disease in SOD1(G93A) mice on an ALS2
      null background. Our data suggest that deficiency in the ALS2 gene does not
      affect the pathogenesis of SOD1(G93A) mice.

PMID- 16973245
TI  - Age-related changes in cognitive conflict processing: an event-related potential
      study.
AB  - Cognitive tasks involving conflicting stimuli and responses are associated with
      an early age-related decline in performance. Conflict and conflict-induced
      interference can be stimulus- or response-related. In classical stimulus-response
      compatibility tasks, such as the Stroop task, the event-related potential (ERP)
      usually reveals a greater negativity on incongruent versus congruent trials which
      has often been linked with conflict processing. However, it is unclear whether
      this negativity is related to stimulus- or response-related conflict, thus
      rendering the meaning of age-related changes inconclusive. In the present study,
      a modified Stroop task was used to focus on stimulus-related interference
      processes while excluding response-related interference. Since we intended to
      study work-relevant effects ERPs and performance were determined in young (about
      30 years old) and middle-aged (about 50 years old) healthy subjects (total n=80).
      In the ERP, a broad negativity developed after incongruent versus congruent
      stimuli between 350 and 650 ms. An age-related increase of the latency and
      amplitude of this negativity was observed. These results indicate age-related
      alterations in the processing of conflicting stimuli already in middle age.

PMID- 16973246
TI  - Synthesis and antibacterial activities of new 1beta-methylcarbapenems having
      aminopyrimidinylthioether moiety.
AB  - The synthesis of new 1beta-methylcarbapenems 1a-d bearing
      aminopyrimidinylthioether moiety at C-5 position of pyrrolidine ring and their
      antibacterial activities are described. All the compounds exhibited potent
      antibacterial activity. Of these carbapenems, 1d showed the best combination of
      antibacterial activity and stability to dehydropeptidase-I (DHP-I).

PMID- 16973247
TI  - Increased potency of BioThrax anthrax vaccine with the addition of the C-class
      CpG oligonucleotide adjuvant CPG 10109.
AB  - The inclusion of an adjuvant, in addition to the existing aluminum hydroxide, in
      the formulation of the licensed anthrax vaccine BioThrax may have the potential
      to positively modify immune responses. Some potential desirable outcomes from the
      inclusion of an additional adjuvant include increased immune response kinetics,
      increased response rates, more prolonged antibody decay rates, and the ability to
      use less antigen per dose or fewer doses to achieve immunity. One promising group
      of adjuvants that is being investigated with a variety of vaccines and which has
      been shown to cause many of these effects are oligonucleotides which contain
      unmethylated CpG motifs. The C-class oligonucleotide CPG 10109, constructed of a
      mixed phosphorothioate/phosphodiester backbone and containing 3 CpG motifs, was
      added to various dilutions of BioThrax and used in mouse and guinea pig
      immunogenicity studies. Anti-protective antigen (PA) IgG ELISAs and the anthrax
      toxin neutralization assay (TNA) were performed on serum samples from both
      species. Anti-PA IgG and TNA responses were approximately 10-fold higher after a
      single dose of undiluted or diluted BioThrax upon addition of 100 microg CPG
      10109 in the mouse regardless of the route of immunization. Responses were also
      significantly greater in the guinea pig after receiving CpG-adjuvanted undiluted
      BioThrax or CpG-adjuvanted BioThrax diluted 1:5, 1:10 or 1:30 compared to those
      achieved with BioThrax alone. A guinea pig spore challenge study showed that a
      single injection of BioThrax vaccine diluted 1:10 in the presence of 25 microg
      CPG 10109 was as protective as undiluted BioThrax, whereas a single injection of
      BioThrax diluted 1:10 was not protective. Taken together with the results from
      the immunogenicity studies, these results suggest that a CpG adjuvant could be
      used to reduce the dose of active ingredient required to elicit a protective
      response, and could lead to improved immune response kinetics.

PMID- 16973248
TI  - N-trimethyl chitosan (TMC) nanoparticles loaded with influenza subunit antigen
      for intranasal vaccination: biological properties and immunogenicity in a mouse
      model.
AB  - In this study, the potential of N-trimethyl chitosan (TMC) nanoparticles as a
      carrier system for the nasal delivery of a monovalent influenza subunit vaccine
      was investigated. The antigen-loaded nanoparticles were prepared by mixing a
      solution containing TMC and monovalent influenza A subunit H3N2 with a
      tripolyphosphate (TPP) solution, at ambient temperature and pH 7.4 while
      stirring. The nanoparticles had an average size of about 800 nm with a narrow
      size distribution and a positive surface charge. The nanoparticles showed a
      loading efficiency of 78% and a loading capacity of 13% (w/w). It was shown that
      more than 75% of the protein remained associated with the TMC nanoparticles upon
      incubation of the particles in PBS for 3h. The molecular weight and antigenicity
      of the entrapped hemagglutinin was maintained as shown by polyacrylamide gel
      electrophoresis and Western blotting, respectively. Single i.n. or i.m.
      immunization with antigen-loaded TMC nanoparticles resulted in strong
      hemagglutination inhibition and total IgG responses. These responses were
      significantly higher than those achieved after i.m. administration of the subunit
      antigen, whereas the IgG1/IgG2a profile did not change substantially. The i.n.
      administered antigen-TMC nanoparticles induced higher immune responses compared
      to the other i.n. antigen formulations, and these responses were enhanced by i.n.
      booster vaccinations. Moreover, among the tested formulations only i.n.
      administered antigen-containing TMC nanoparticles induced significant IgA levels
      in nasal washes of all mice. In conclusion, these findings demonstrate that TMC
      nanoparticles are a potent new delivery system for i.n. administered influenza
      antigens.

PMID- 16973249
TI  - Ground-level ozone in China: distribution and effects on crop yields.
AB  - Rapid economic development and an increasing demand for food in China have drawn
      attention to the role of ozone at pollution levels on crop yields. Some
      assessments of ozone effects on crop yields have been carried out in China.
      Determination of ozone distribution by geographical location and resulting crop
      loss estimations have been made by Chinese investigators and others from abroad.
      It is evident that surface level ozone levels in China exceed critical levels for
      occurrence of crop losses. Current levels of information from ozone dose/response
      studies are limited. Given the size of China, existing ozone monitoring sites are
      too few to provide enough data to scale ozone distribution to a national level.
      There are large uncertainties in the database for ozone effects on crop loss and
      for ozone distribution. Considerable research needs to be done to allow accurate
      estimation of crop losses caused by ozone in China.

PMID- 16973250
TI  - Formation of mutagenic heterocyclic aromatic amines in fried pork from Duroc and
      Landrace pigs upon feed supplementation with creatine monohydrate.
AB  - Heterocyclic aromatic amines (HAA) have been shown to induce tumours at various
      organ sites in experimental animal studies and high levels of dietary intake of
      HAA have been associated with increased cancer risk in humans. These HAA are
      formed in meat upon heating from precursors such as amino acids, reducing sugars
      and creatine or creatinine. Groups of ten Duroc and ten Landrace pigs received
      feed supplemented with creatine monohydrate (CMH) for five days prior to
      slaughter at dose levels of 12.5, 25 and 50 g per animal per day. Ten control
      animals of each breed received the non-supplemented feed. Meat from Duroc pigs
      had been shown to respond to CMH supplementation with regard to waterholding
      capacity, juiciness, post slaughter pH and colour parameters, meat from Landrace
      pigs was unaffected. Indeed, while creatine phosphate levels in meat from Duroc
      pigs increased in a dose-dependent manner with CMH supplementation, no effect was
      observed in meat from Landrace pigs. Meat slices from longissimus dorsi were
      fried and considerable mutagenic activity was detected in meat extracts in
      Salmonella typhimurium YG1019 in the presence of rat-liver homogenate. However,
      no effect of breed or CMH supplementation was observed in fried pork on the
      formation of HAA determined as mutagenic activity. It may be concluded that feed
      supplementation with CMH at levels up to 50 g per day for five days prior to
      slaughter does not increase the level of heterocyclic aromatic amines detected as
      mutagenic activity formed upon frying of pork.

PMID- 16973251
TI  - Dentin micro-architecture using harmonic generation microscopy.
AB  - OBJECTIVES: We present a novel way to create high-resolution three-dimensional
      images of tooth dentin by harmonic generation scanning laser microscopy. METHODS:
      The images were taken using a pulsed infrared laser. Three-dimensional
      reconstruction enables the visualization of individual tubules and the collagen
      fibrils mesh around them with an optical resolution of approximately 1 microm.
      RESULTS: The images show micro-morphological details of the dentinal tubules as
      well as the collagen fibrils at a depth of up to about 200 microm. The data show
      that while collagen fibrils are organized in planes perpendicular to the tubules,
      close to the dentin enamel junction they lie also along the long axis of the
      tubules. CONCLUSIONS: The unique 3D information opens the opportunity to study
      the collagen fibril arrangement in relation to the tubule orientation within the
      dentin matrix, and may be applied to study the micro-morphology of normal versus
      altered dentin.

PMID- 16973252
TI  - Comparison between effectiveness of a low-viscosity glass ionomer and a resin
      based glutaraldehyde containing primer in treating dentine hypersensitivity--a
      25.2-month evaluation.
AB  - OBJECTIVES: The null-hypothesis tested was; there is no difference in
      effectiveness between a new low-viscosity glass ionomer and a resin-based
      glutaraldehyde containing primer in treating hypersensitive teeth after 2 years.
      METHODS: Using a split-mouth design, hypersensitive teeth in 14 adult patients
      were randomly assigned to 2 treatment groups. Hypersensitive tooth surfaces were
      covered with a low-viscosity glass ionomer (Fuji VII) and a resin-based
      glutaraldehyde containing primer (Gluma Desensitizer). The discomfort interval
      scale (DIS) ranging from 0 to 4 was used to test the level of hypersensitivity
      before and after treatment, and at 3 months using compressed air blown for 2 s,
      and at 1 and 25.2 months using a telephone interview. Differences between and
      within the treatment groups were tested using the sign rank test. RESULTS:
      Evaluations in the gluma group were discontinued after 3 months. The mean DIS
      score for hypersensitive teeth in the glass ionomer group was statistically
      significantly lower than that in the gluma group, immediately after application
      (p=0.0005), after 1 month (p=0.02) and after 3 months (p=0.003). After 3 months,
      11/14 of the hypersensitive teeth in the glass ionomer group and 2/14 in the
      gluma group were free of sensitivity. The mean DIS score for hypersensitive teeth
      in the glass ionomer group remained low after 19.2 months (0.25: S.E.=0.13) and
      25.2 months (0.22: S.E.=0.15). CONCLUSIONS: The null-hypothesis was rejected. The
      low-viscosity glass ionomer (Fuji VII) is more effective in treating
      hypersensitive teeth than Gluma Desensitizer after 3 months. The positive
      treatment effect of the glass ionomer continued until 25.2 months.

PMID- 16973253
TI  - Clinical failure of class-II restorations of a highly viscous glass-ionomer
      material over a 6-year period: a retrospective study.
AB  - OBJECTIVES: The aim of this retrospective clinical study was to evaluate the
      performance of high-viscosity glass-ionomer cement (GIC) class-II restorations
      over 6 years of clinical service. METHODS: All class-II GIC restorations made in
      1996 and 1997, in regular attending adult patients of a general dental practice
      were selected. Restorations made for temporary function were excluded, as were
      those restorations not made using the main study material: Fuji IX GP (GC).
      Failures were recorded where replacement or repair had occurred. Radiographs were
      evaluated where available. RESULTS: The final study group consisted of 116 class
      II restorations in 72 patients (33 males, 39 females). Distribution of
      restorations was: 30 MO, 40 DO, 46 MOD. Until 18 months no failures were
      observed. From 18 to 42 months survival dropped to 93%. After 42 months failure
      rate increased and at 72 months survival was only 60%. In all but one case the
      recorded reason for replacement or repair was gross loss of GIC in proximal
      areas. No restorations failed because of occlusal wear or isthmus-fractures. On
      radiographs, progressive loss of GIC material in proximal areas, just below
      contact areas, was commonly observed. In absence of adjacent teeth no loss of GIC
      material was observed at proximal surfaces. SIGNIFICANCE: Rising failure rate of
      class-II high-viscosity GIC restorations, due to proximal breakdown was observed.
      We hypothesize that caries-like loss of material as seen on radiographs
      contributes to this phenomenon. Presence of proximal contacts seems to promote
      disintegration of cement.

PMID- 16973254
TI  - New paradigm for prevention of cervical cancer.
AB  - Human papillomavirus (HPV) infection is an event responsible for the development
      of cervical cancer and its premalignant dysplasia. Prophylactic vaccines based on
      virus-like particles (VLPs) have been successfully tested in clinical trials.
      They are safe, close to 100% effective in preventing persistent infection and
      premalignant disease, and are now being introduced onto the market. Vaccination
      should be offered primarily to young girls and adolescents 9-15 years of age.
      Vaccine introduction faces particular problems due to a bias towards sexually
      transmitted diseases and financing, especially in developing countries. However,
      it represents the first vaccine that has the potential to eradicate 70% of
      cervical cancer world wide.

PMID- 16973255
TI  - Interobserver agreement on interpreting hand drawings of colposcopy in women with
      borderline cytology to predict high-grade lesions.
AB  - OBJECTIVE: To assess the interobserver agreement on interpreting hand drawings as
      a colposcopic image recording technique in women with borderline cytology and to
      assess the correlation between colposcopic impression and histological outcome.
      METHODS: We used colposcopic documentation and histology from a cohort study of
      women with borderline dyskaryosis. Four gynecologists and four residents scored
      the same 30 colposcopic documentation forms. RESULTS: There is a good
      interobserver agreement on classifying colposcopic hand drawings as high-grade
      lesions (average kappa 0.58). The interobserver agreement on interpreting
      colposcopic image was higher for the more highly experienced gynecologists than
      for the residents. The agreement between colposcopic impression and histological
      outcome is poor (kappa 0.17) among the observers. CONCLUSIONS: Hand drawings are
      a reliable recording technique of interpreting colposcopic impression documented
      as high-grade lesion. However, the correlation between colposcopic impression and
      histological outcome is still poor in women with minor cytological abnormalities.

PMID- 16973256
TI  - A comparative study of the effect of raloxifene and gosereline on uterine
      leiomyoma volume changes and estrogen receptor, progesterone receptor, bcl-2 and
      p53 expression immunohistochemically in premenopausal women.
AB  - OBJECTIVE: To compare the mechanism of action of raloxifene and gosereline
      induced shrinkage of leiomyomas via estrogen receptor, progesterone receptor, bcl
      2 and p53 expression immunohistochemically. STUDY DESIGN: Thirty-two
      premenopausal women affected by uterine leiomyomas were randomized into two equal
      groups. Group A was treated with gosereline (3.6 mg subcutaneous injection
      monthly) and group B was treated with raloxifene (60 mg daily per os) for 3
      months before undergoing surgery. At entry and at the end of the treatment the
      leiomyoma volume was measured ultrasonografically and the volume change was
      calculated. Immunohistochemical detection of estrogen receptor (ER), progesterone
      receptor (PR), bcl-2 and p53 were performed on leiomyoma tissue samples from
      group A, group B and the matched-control group. H-scores for ER, PR, bcl-2 and
      p53 were calculated. The mean volume changes of leiomyomas and
      immunohistochemical H-score differences of ER, PR, bcl-2 and p53 were compared
      between groups. RESULTS: The leiomyoma volume decreased significantly after
      treatment in gosereline group from baseline of 65 cm(3) to 35 cm(3), and in
      raloxifene group from 68 cm(3) to 50 cm(3), p<0.05. The difference between the
      before and after treatment leiomyoma volumes between the two treatments was not
      statistically significant. H-score of ER expression was significantly lower in
      gosereline group compared to control group (54.4 versus 113.2, p = 0.001),
      whereas H-score of PR expression was significantly lower with both gosereline and
      raloxifene groups compared to control group (64.8 for gosereline versus 94.6 for
      control, 73.6 for raloxifene versus 94.6 for control, p = 0.001). The bcl-2
      expression was higher in both gosereline and raloxifene groups compared to
      control group (173.7 for gosereline versus 94.7 for control, 179.7 for raloxifene
      versus 94.7 for control, p = 0.001). The p53 expression was only lower with
      gosereline than the control group (169.4 versus 205.6, p = 0.001), whereas there
      was no significant change between the raloxifene group and the control group
      (201.9 versus 205.6) (p>0.05). CONCLUSION: Raloxifene was as effective as
      gosereline in reducing leiomyoma volumes. Decreased PR expression may be a
      mechanism for tumor growth reduction in raloxifene treatment. In both treatment
      modalities, the mechanism of shrinkage of leiomyomas could not be increased
      apoptosis mediated by bcl-2 and p53 expression and should be investigated by
      further studies.

PMID- 16973257
TI  - Photophysics of ANS. II: Charge transfer character of near-UV absorption and
      consequences for ANS spectroscopy.
AB  - We continue our investigation of the photophysics of 1,8
      anilinonaphthalenesulfonate in protein and solvent systems. In this report, we
      concentrate on the nature of the excited states as observed in UV spectra. We
      develop a fairly general formalism for handling the coupled transitions we
      observe in the partial systems aniline and naphthalene. We assign one of the near
      UV transitions, which is more clearly discernible in congeners of 1,8-ANS, but
      still present in 1,8-ANS as we postulate it, to a charge-transfer band. The other
      transition is from aniline itself. The expected energies of these now coupled
      bands in anilinonaphthalene and ANS are calculated, and the transition dipole
      moment for these transitions is derived.

PMID- 16973258
TI  - Nomograms and medicine.

PMID- 16973260
TI  - The evolution of ED therapy in the 21st century.

PMID- 16973261
TI  - TC incidence increasing: spread the word.

PMID- 16973262
TI  - Ecotoxicological evaluation of the wastewater treatment process of the sewage
      treatment plant of Thessaloniki, Greece.
AB  - The LUMISTox toxicity test was employed to assess the removal of municipal
      wastewater toxicity during the biological treatment with activated sludge in the
      wastewater treatment plant of Thessaloniki, Greece. Possible associations of
      toxicity data with chemical parameters of organic pollution of wastewaters,
      namely BOD(5), COD, DOC, SS and persistent organic pollutants (POPs) were also
      investigated. Toxicity and chemical parameters were concurrently measured at
      three sampling points of the treatment plant, the entrance of the unit (raw
      wastewater, RW), the effluent of the secondary sedimentation tank (SSE), and the
      final sewage sludge (FS). Substantial reduction of toxicity was observed from RW
      to SSE (mean+/-S.D. of bioluminescence inhibition 36+/-9.4% and 13+/-4.0%,
      respectively) indicating removal of toxicants during primary and secondary
      clarification, also suggesting that a large part of the toxicity measured is
      attributed to the biodegradable fraction of the organic content of wastewater.
      Significant positive correlations were observed between % inhibition values and
      wastewater parameters (BOD, COD, SS). In sludge, correlations were in general
      poor. Negative strong correlation was observed between EC(20/15) and TOC
      suggesting that the organic content of sludge contributes to the toxicity
      measured. Toxicity was positively correlated with the concentrations of certain
      POPs in RW, while weaker negative correlations were observed in SSE. Correlations
      in sewage sludge were less significant. It was concluded that toxicity testing is
      a useful tool supplementing chemical analyses in the evaluation of the potential
      hazard from effluent discharges and disposal of waste sludge.

PMID- 16973263
TI  - Polycyclic aromatic hydrocarbons sorbed on soils: a short review of chemical
      oxidation based treatments.
AB  - A brief review is completed on the chemical oxidation of PAHs contaminated soils.
      Previously, the adsorption and extraction processes are also documented and
      discussed. The tree main technologies reported in the specialised literature
      include the use of ozone, hydrogen peroxide (with or without ferrous iron
      addition) and high temperature pressurized water (both in sub- and super-critical
      conditions) in the presence of an added oxidant like hydrogen peroxide, oxygen,
      persulfate, etc. Each process is detailed by the influence of the main operating
      variables reported in the literature (i.e. presence of organic matter, soil type,
      reagents dosage, etc.), the kinetics and the description of integrated treatments
      (i.e. chemical oxidation + biodegradation).

PMID- 16973264
TI  - Eliminating toxic compounds by composting olive mill wastewater-straw mixtures.
AB  - The present work studies the changes occurring in organic matter, phenols and
      biotoxicity on composting olive mill wastewater with barley straw. The total
      organic matter decreased, a drop of 25% was reached after the stabilization phase
      and 52% at the end of the maturation phase. Degradation of the phenols reached
      54% and 95%, respectively, after these periods. The toxicity of the water
      extract, evaluated by the Photobacterium phosphoreum fluorescence, decreased to
      disappear after only 2 months of composting. This trend was confirmed by the
      tight correlation between the physico-chemical and toxicity parameters,
      indicating that the degradation of organic matter leads to a strong reduction of
      the C/N ratio and of toxicity. The results obtained indicate a normal process of
      humification occurring during the composting of the formerly highly toxic olive
      mill wastewater-straw mixture and resulting in a product, which has good
      agricultural properties as organic fertilizer.

PMID- 16973265
TI  - Time-dependent sorption of norflurazon in four different soils: use of beta
      cyclodextrin solutions for remediation of pesticide-contaminated soils.
AB  - High pesticide concentrations in soil from spills or discharges can result in
      point-source contamination of ground and surface waters. Cost-effective
      technologies are needed for on-site treatment that meet clean-up goals and
      restore soil function. Remediation is particularly challenging when a mixture of
      pesticides is present. beta-Cyclodextrins (BCD) solutions are employed to enhance
      the aqueous solubility of a hydrophobic organic compound. The interaction of
      norflurazon (NFL) with BCD yielded the formation of inclusion complexes at a 1:1
      stoichiometric ratio in solution. The change of the sorption parameter K(d) as
      affected by the time, and desorption studies of NFL previously adsorbed on four
      different soils with different characteristics have been performed in the
      presence of 0.01 M BCD or 0.01 M Ca(NO(3))(2) acting as extractant solutions. NFL
      sorption increased with the residence time in soil, making it more resistant to
      be desorbed. Likewise, leaching experiments were performed in packed soil columns
      eluting initially with distilled water, with the aim to simulate the herbicide
      drainflow losses because of rainfall, approaching to a more realistic
      environment, and later with 0.01 M BCD solutions to extract the residual NFL
      bound. The results showed that removal efficiencies of the different flushing
      systems were significantly influenced by their affinity and selectivity for the
      contaminants in the soil matrix as well as BCD adsorption on soils, since this
      could act like a bridge between pesticide molecule and soil particles increasing
      the stay of NFL in soil. These results are further information to be in condition
      to predict the potential effect of the BCD solutions on soil chemical
      decontamination in the field situation assessing the likelihood for
      bioremediation of a pesticide contaminated-soil, since the increasing in
      hydrosolubility of the contaminants means the first step before microorganism
      uptaken.

PMID- 16973266
TI  - Burning characteristics and emission products related to metallic content in
      incense.
AB  - This study mainly compared particulate emission factors of nine popular incense.
      The influence of metallic contents upon the burning rate, ash and particulate
      emission factors of combustion was discussed. The contents of Ca and K were the
      highest among all metallic elements in the raw materials of the incense (the
      geometric mean contents 8.7 and 2.5mgg(-1), respectively), followed by Al, Mg,
      Fe, Na (0.1-1.0mgg(-1)) and Ba, then Sr, Mn, Cu and Zn (<0.01-0.1mgg(-1)). Most
      calcium existed as inorganic salts, such as CaCO(3). Under the same burning
      conditions, the particulate generation rates are similar (0.50mgmin(-1)+/-9%)
      among different types of incense-the shorter the combustion duration of a stick,
      the lower the total suspended particulate emission. Additionally, with the same
      incense weight burned, the greater the emission of ash is, the lower the emission
      of suspended particulate. It is recommended that consumers select incense which
      produces more ash, hence less particulate, to minimize the threat to their'
      health. Additionally, when the total metallic content (with Ca as the major
      component) was lower than 2% of the raw materials, properly increasing the total
      metallic content (from 0.5 to 2.0%) can effectively reduce the level of
      particulates (about 40%) during the combustion.

PMID- 16973267
TI  - Effects of insufficient air injection on methanogenic Archaea in landfill
      bioreactor.
AB  - In this study, methanogenic Archaea diversity in an aerated landfill bioreactor
      filled with co-disposed incineration bottom ashes and shredded incombustible
      wastes was monitored and analyzed as a function of time using molecular
      techniques. Besides, the effects of insufficient air injection on the bioreactor
      performance and methanogenic diversity were evaluated thoroughly. Results
      indicated that rapid bio-stabilization of solid waste are possible with aerated
      landfill bioreactor at various oxygen and oxidation reduction potential levels.
      Slot-blot hybridization results of leachate samples collected from aerated
      landfill bioreactor showed that archaeal and bacterial activities increased as
      stabilization accelerated and bacterial populations constituted almost 95% of all
      microorganisms. The results of slot-blot hybridization and phylogenetic analysis
      based on 16S rRNA gene revealed that Methanobacteriales and Methanomicrobiales
      were dominant species at the beginning while substituted by Methanosarcina
      related methanogens close to the end of the operation of bioreactor.

PMID- 16973268
TI  - Thyroidectomy alters the daily pattern of expression of the clock protein, PER2,
      in the oval nucleus of the bed nucleus of the stria terminalis and central
      nucleus of the amygdala in rats.
AB  - A role for thyroid hormones in the regulation of the rhythmic expression of
      circadian clock genes is suggested by the finding that surgical removal of the
      thyroid gland alters circadian behavioral and endocrine rhythms in rodents.
      Virtually nothing is known about the role of thyroid hormones in the regulation
      of clock genes responsible for the generation of circadian rhythmicity. To study
      this issue, we assessed in rats the effect of thyroidectomy/parathyrodectomy
      (TPX) on the expression of the clock protein, PER2, in the suprachiasmatic
      nucleus (SCN), the master circadian clock, and in a number of key limbic
      forebrain structures, the oval nucleus of the bed nucleus of the stria terminalis
      (BNSTov), the central nucleus of the amygdala (CEA), the basolateral amygdala
      (BLA) and the dentate gyrus (DG). TPX significantly altered the normal daily
      pattern of PER2 expression in the BNSTov and CEA, but had no effect on PER2
      expression in the SCN, BLA and DG. Thus, although thyroid hormones modulate PER2
      expression in the brain, the effect is tissue specific and therefore likely not
      to be mediated by a direct effect of the hormone on gene expression.

PMID- 16973269
TI  - Expression of IL-1beta in supraspinal brain regions in rats with neuropathic
      pain.
AB  - We examined mRNA expression of the pro-inflammatory cytokine IL-1beta in the
      brainstem, thalamus, and prefrontal cortex in two rat models of neuropathic pain.
      Rats received a neuropathic injury: spared nerve injury (SNI) or chronic
      constriction injury (CCI), sham injury, or were minimally handled (control).
      Neuropathic pain-like behavior was monitored by tracking tactile thresholds. SNI
      injured animals showed a robust decrease in tactile thresholds of the injured
      foot, while CCI-injured animals did not show tactile threshold changes. Ten or 24
      days after nerve injury, IL-1beta gene expression in the brain was determined by
      RT-PCR. IL-1beta expression changes were observed mainly at 10 days after injury
      in the SNI animals, contralateral to the injury side, with increased expression
      in the brainstem and prefrontal cortex. The results indicate that neuro-immune
      activation in neuropathic pain conditions includes supraspinal brain regions,
      suggesting cytokine modulation of supraspinal circuitry of pain in neuropathic
      conditions.

PMID- 16973270
TI  - Changes in cerebral blood flow under the prone condition with and without
      massage.
AB  - To investigate changes in regional cerebral blood flow (rCBF) under the prone
      condition with and without light massage on the back, we measured rCBF
      quantitatively in healthy human subjects using positron emission tomography with
      H(2)15O. Biochemical tests showed that the light massage (palm-pressure) reduced
      levels of stress-related serum cortisol and salivary stress protein chromogranin
      A measured after the PET examination. Absolute rCBF significantly increased in
      the parietal cortex (precuneus) under the prone condition compared with the
      supine condition, and this rCBF increase was in parallel with comfortable
      sensation and slowing heart rate during the massage. Correlation analysis in
      statistical parametric mapping showed that the amygdalar and basal forebrain rCBF
      correlated with parasympathetic function (heart rate reduction), indicating
      involvement of the forebrain-amygdala system in mediating activities in the
      autonomic nervous system in the presence of comfortable sensation. To conclude,
      prone posture itself can stimulate the precuneus region to raise awareness, and
      the light massage on the back may help accommodate the brain to comfortable
      stimulation.

PMID- 16973271
TI  - In vitro efficacy of three lazaroids in a model of acute chemical neuronal
      hypoxia.
AB  - Free radicals are highly reactive chemicals containing an unpaired electron and
      are normally produced by the cellular metabolism. But the excessive production of
      free radicals by oxidative stress is engaged in a large variety of diseases. The
      goal of this work was to determine the neuroprotective effect of free radical
      scavengers in an acute in vitro model of neuronal hypoxia. Primary cultures of
      cortical neurons of rats were exposed to 0.5 mM sodium cyanide for 6 h. Neuron
      death was evaluated with a lactate dehydrogenase assay. This mortality was up to
      66.5% in cultures exposed to 0.5 mM sodium cyanide compared to non-exposed
      control cultures. Three lazaroids (U-74500A, U-74389G, U-83836E), were added to
      cultures, at different concentrations (10(-7)-10(-5) M), simultaneously with
      cyanide, during 6h. These agents caused a reduction in neuronal death, compared
      to exposed cultures. Efficacy varied with lazaroid compounds and U-74500A
      decreased neuronal death to 37-23.5%, U-74389G to 37-32%, and U-83836E to 42-33%.
      These results suggest a partial neuroprotective effect of free radical scavengers
      since lipid peroxidation is a key cellular event in neuronal injury, and its
      inhibition with lazaroids could help to reduce brain ischaemic lesions.

PMID- 16973272
TI  - Hepatocyte growth factor attenuates cerebral ischemia-induced increase in
      permeability of the blood-brain barrier and decreases in expression of tight
      junctional proteins in cerebral vessels.
AB  - Hepatocyte growth factor (HGF) exerts its physiological activities as that of an
      organotropic factor for regeneration and can prevent ischemia-induced injuries;
      however, its effect and mechanism of action under in vivo pathophysiological
      conditions remains to be determined. Recently, we demonstrated that treatment
      with human recombinant HGF (hrHGF) attenuated the disruption of the blood-brain
      barrier (BBB) observed after microsphere embolism-induced sustained cerebral
      ischemia. To see if tight junctional proteins were involved in this attenuation,
      in the present study, we investigated the effects of HGF on the levels of
      occludin and zonula occludens (ZO)-1 in cerebrovascular endothelial cells after
      microsphere embolism. Sustained cerebral ischemia was induced by the injection of
      700 microspheres (48 microm diameter) into the right internal carotid artery of
      rats. hrHGF was injected into the right ventricle of the brain by using an
      osmotic pump at a dose of 30 microg/7 days per animal. The levels of tight
      junctional proteins in the endothelial cells were examined by immunohistochemical
      analysis. Treatment with hrHGF attenuated the decrease in the expression of
      occludin and ZO-1 proteins in the endothelial cells that occurred after sustained
      cerebral ischemia. Furthermore, treatment with hrHGF resulted in retention of
      these tight junctional proteins in fluorescein isothiocyanate (FITC)-albumin
      perfused cerebral vessels, which did not leak FITC-albumin in the ipsilateral
      cortex. These results suggest that HGF-mediated maintenance of the tight
      junctional proteins in the endothelial cells may be a possible mechanism for the
      protective effect of HGF against the disruption of the BBB after cerebral
      ischemia.

PMID- 16973273
TI  - Selective susceptibility of different populations of sympathetic neurons to
      diabetic neuropathy in vivo is reflected by increased vulnerability to oxidative
      stress in vitro.
AB  - Diabetes is the major cause of autonomic neuropathy in humans. Sympathetic
      neurons from the celiac/superior mesenteric ganglia (CG/SMG) develop neuropathic
      changes in diabetes whereas sympathetic superior cervical ganglion (SCG) neurons
      do not. Glucose-induced oxidative stress is proposed as a major factor in the
      development of diabetic neuropathy. The aim of this study was to investigate
      whether sympathetic neurons that develop neuropathy in diabetes are more
      susceptible to oxidative stress. Explants of CG/SMG and SCG from control adult
      rats were cultured in media free of serum and NGF, exposed to menadione for 48 h
      to induce oxidative stress and assessed for neuronal viability, TUNEL-positive
      nuclei and tyrosine hydroxylase- (TH)-immunoreactivity. TH-immunoreactivity was
      also assessed in ganglia from control and 8 week streptozotocin-diabetic rats.
      Menadione caused a concentration-dependent loss of neuronal viability and
      increase in TUNEL staining in both ganglia. However, at low concentrations,
      menadione had a significantly greater effect (p<0.01) on CG/SMG neurons than SCG
      neurons. At 1 nM, menadione caused a significant increase (p<0.05) in the number
      of CG/SMG neurons containing intense TH-immunoreactivity without affecting SCG
      neurons. Similarly, 8 weeks streptozotocin-induced diabetes resulted in a
      significant increase (p<0.05) in intensely fluorescent TH-containing CG/SMG
      neurons but not SCG neurons. This is the first demonstration that oxidative
      stress in vitro causes the same accumulation of TH in CG/SMG neurons as is
      observed following streptozotocin-induced diabetes in vivo. Furthermore, the
      selective vulnerability of CG/SMG neurons to diabetes is reflected by increased
      sensitivity to oxidative stress.

PMID- 16973274
TI  - Neither sequence variation in the IL-10 gene promoter nor presence of IL-10
      protein in the cerebral cortex is associated with Alzheimer's disease.
AB  - Interleukin 10 (IL-10) is an important anti-inflammatory cytokine produced in
      response to neuroinflammation and might be involved in modulating the progression
      of Alzheimer's disease (AD) through inhibiting the action of pro-inflammatory
      cytokines. We have used immunohistochemistry, Western blotting, real time-PCR (RT
      PCR) on frontal (BA 6/24) and temporal (BA 20-22) neocortex and hippocampus from
      AD and control brains as well as genetic association analysis to address the
      possible involvement of IL-10 in AD. Expression of IL-10 in AD and control brains
      at both protein and mRNA levels were detected. However, the level of expression,
      particularly of IL-10 protein, varied considerably in individual brains and we
      did not find a significant difference between AD and controls. Using direct
      sequencing we examined five single nucleotide polymorphisms (SNPs) (-3538, -1354,
      -1087, -824, -597) and two microsatellites (IL-10-G, IL-10-R) in the promoter
      region of the IL-10 gene. None of the identified SNPs were found to be associated
      with AD either individually or as haplotypes. Levels of IL-10 protein and gene
      expression examined also did not appear to be related to AD. Despite this being a
      relatively small sample, these data suggest that IL-10 does not play a major role
      in the development of AD.

PMID- 16973275
TI  - Leptin inhibits 1-methyl-4-phenylpyridinium-induced cell death in SH-SY5Y cells.
AB  - Leptin is best known as a key satiety factor and it is now appreciated that
      leptin has many additional biological functions. Our previous study suggested
      that leptin-resistant obesity might exacerbate 1-methyl-1,2,3,6
      tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity in vivo. Here, we
      ask whether leptin might protect neuronal cells against 1-methyl-4-pyridinium
      (MPP+)-induced cell death. We used differentiated SH-SY5Y cells and investigated
      plausible cytoprotective signalling mechanisms. When SH-SY5Y cells were
      maintained under serum-free conditions for 48 h, MPP+ (1 mM) reduced cell
      viability to 66.8% of the drug-free control, and leptin significantly inhibited
      cell death in a dose-dependent manner. Among inhibitors of known leptin
      signalling pathways, a PI-3K inhibitor inhibited the protective effect of leptin
      during MPP+ exposure, whereas inhibitors affecting the Janus kinase/signal
      transducers and activators of transcription (JAK/STAT) or mitogen-activated
      protein kinase (MAPK) pathways did not influence cell viability. We used
      immunoblotting to show that the PI-3K/Akt pathway was involved in the effect of
      leptin on cell viability. In conclusion, our results show that leptin exercises a
      cytoprotective effect against MPP+ -induced cell death and that this effect is
      dependent on activation of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway
      in SH-SY5Y cells. The data tend to support our previous results in vivo.

PMID- 16973276
TI  - Extracellular signal-regulated kinases are not involved in activity-dependent
      survival or apoptosis in cerebellar granule neurons.
AB  - Cerebellar granule neurons (CGNs) depend on potassium depolarization for survival
      and undergo apoptosis when deprived of depolarizing concentration of potassium.
      Extracellular signal-regulated kinases (ERK1/2) are thought to be activated in
      response to potassium depolarization and responsible for the activity-dependent
      survival in CGNs, but one recent study has revealed that ERK1/2 is activated by
      potassium deprivation and is required for apoptosis of CGNs. In this study we
      showed that ERK1/2 was inactivated, rather than activated, by potassium
      deprivation, indicating a lack of ERK1/2 involvement in potassium deprivation
      induced apoptosis. Furthermore, suppression of potassium depolarization-induced
      activation of ERK1/2 with chemical inhibitor U0126 or PD98059 had no influence on
      the pro-survival effect of potassium depolarisation. Thus, ERK1/2 was not
      required for potassium depolarization-dependent survival of CGNs. Taken together,
      our findings suggest that ERK1/2 is not involved in activity-dependent survival
      or apoptosis of CGNs.

PMID- 16973277
TI  - Prenatal development of transient receptor potential vanilloid 1-expressing
      primary sensory projections to sacral autonomic preganglionic neurons.
AB  - The visceral reflexes of the pelvic organs are mediated by connections between
      primary afferents innervating the pelvic organs and parasympathetic preganglionic
      neurons in the intermediolateral column of the sacral spinal cord. The present
      immunohistochemical study revealed many varicosities expressing transient
      receptor potential vanilloid 1 (TRPV1) that were closely apposed to the
      preganglionic neuronal perikarya at embryonic day 16 in mice. Many, but not all,
      varicosities expressing TRPV1 in the intermediolateral column were also
      immunopositive for calcitonin gene-related peptide. In contrast, no nerve fibers
      expressing TRPV1 projected to the sympathetic preganglionic cell column in the
      lumbar spinal cord in prenatal stages. The results of the present study raised
      the possibility that the primary afferents transmit signals elicited by the
      activation of TRPV1 receptors to the sacral parasympathetic preganglionic
      neurons. Thus, the functional circuit for pelvic spinal reflexes, such as
      micturition induced by urine influx, might develop in the prenatal stages in
      mice.

PMID- 16973278
TI  - Phospholipase D1 is up-regulated in the mitochondrial fraction from the brains of
      Alzheimer's disease patients.
AB  - Mitochondrial dysfunction may play an important role in sporadic Alzheimer's
      disease (AD) progression. Recently, we have reported that amyloid precursor
      protein (APP) stimulates phospholipase D (PLD) activity and beta-amyloid (Abeta)
      region of APP is involved in the interaction with PLD1. To elucidate the
      involvement of PLD in the pathophysiology of AD, we examined the expression of
      PLD1 and alteration of membrane phospholipid in mitochondrial membranes of
      control and AD brains using Western blot and phospholipid analysis by thin layer
      chromatography (TLC). We have found that protein expression of PLD1 was
      significantly increased in mitochondrial fraction of brains of AD patients
      compared with that in control brains. Furthermore, the concentration of
      mitochondrial phospholipids such as phosphatidylcholine (PC) and
      phosphatidylethanolamine (PE) was increased and the content of phosphatidic acid
      (PA), a product of PLD activity, was up-regulated in the mitochondrial membrane
      fractions of AD brain compared with that of control brain. These results suggest
      that up-regulation of PLD1 in the mitochondrial fraction of AD brain might affect
      the composition of membrane phospholipids and provide a clue to the mechanism
      underlying the mitochondrial dysfunction associated with AD.

PMID- 16973279
TI  - Decreased plasma adiponectin concentration in major depression.
AB  - Adiponectin is the most abundant adipose-derived plasma protein. Recently
      adiponectin levels have been linked to most variables of metabolic syndrome and
      conventional risk factors for cardiovascular disease. However, its relation with
      major depression is yet unclear. We evaluated plasma adiponectin levels in 32
      first-episode drug-naive major depression (DSM-IV-TR) patients without
      conventional risk factors for cardiovascular disease and 32 matched healthy
      subjects. Major depression patients displayed lower adiponectin plasma levels
      compared to controls (P<0.01). Adiponectin significantly correlated with
      depression severity, as assessed by HAM-D (rho=0.83, P<0.001). This study shows
      decreased plasma adiponectin concentrations in major depression patients and
      relates adiponectinemia reduction to major depression severity.

PMID- 16973280
TI  - Association between the C957T polymorphism of the dopamine D2 receptor gene and
      schizophrenia.
AB  - The aim of this study was to investigate the relationship between the functional
      C957T single-nucleotide polymorphism of the dopamine D2 receptor (DRD2) gene and
      the risk for schizophrenia. We therefore conducted a case-control association
      study of 188 Finnish schizophrenia patients meeting the DSM-IV criteria and 384
      healthy controls. The 5' nuclease assay (TaqMan) was used to determine genotypes.
      A greater proportion of patients with schizophrenia than healthy controls were C
      allele carriers (odds ratio 1.5, 95% confidence interval (CI) 1.0-2.3, P=0.05).
      Our results are in agreement with an earlier association study suggesting that
      the C957T C-allele plays a role in the genetic vulnerability for schizophrenia
      and support the involvement of the DRD2 gene in schizophrenia pathogenesis.

PMID- 16973281
TI  - Klotho is a genetic risk factor for ischemic stroke caused by cardioembolism in
      Korean females.
AB  - An aging-suppressor gene, klotho, is a candidate factor for vascular disease
      because its deficiency leads to impaired endothelium-dependent vasodilation and
      impaired angiogenesis. We investigated the association of polymorphisms in klotho
      with ischemic stroke. We searched for sequence variants in promoter and exons of
      klotho gene. For the association study, selected variants were genotyped in
      control subjects and in patients with ischemic stroke and vascular dementia. The
      association with ischemic stroke was further investigated with its subtypes
      classified based on Trial of Org 10172 in Acute Stroke Treatment (TOAST). No
      significant association was observed for both G-395A and C1818T with ischemic
      stroke and vascular dementia (P>0.05). The analysis with subtypes of ischemic
      stroke revealed the associations that the A allele of G-395A increased the risk
      of cardioembolic stroke (CE, OR=2.60; P=0.006), and subjects carrying the A
      allele were susceptible to CE in both of dominant (AA+GA versus GG; OR=2.50;
      P=0.046) and recessive (AA versus GA+GG; OR=6.52; P=0.007) models. Further
      analysis of data partitioned by gender showed that the associations of G-395A
      with CE only existed in women (A versus G; OR=4.33; P=0.002), AA+GA versus GG;
      OR=5.68; P=0.014, and AA versus GA+GG; OR=9.07; P=0.012), but the significance
      disappeared in men (P>0.05). The sequence variant of G-395A in klotho might be a
      genetic risk factor for CE in females.

PMID- 16973282
TI  - The protective effect of hepatocyte growth factor against cell death in the
      hippocampus after transient forebrain ischemia is related to the improvement of
      apurinic/apyrimidinic endonuclease/redox factor-1 level and inhibition of NADPH
      oxidase activity.
AB  - Early oxidative DNA damage is regarded to be an initiator of neuronal apoptotic
      cell death after cerebral ischemia. Although evidence suggests that HGF has the
      ability to protect cells from oxidative stress, it remains unclear as to how HGF
      suppresses oxidative DNA damage after cerebral ischemia. Apurinic/apyrimidinic
      endonuclease/redox factor-1 (APE/Ref-1) is a multifunctional protein in the DNA
      base repair pathway that is responsible for repairing apurinic/apyrimidinic sites
      in DNA after oxidation. We demonstrated that both the immunoreactivity and the
      number of APE/Ref-1-positive cells in the hippocampal CA1 region were decreased
      after transient forebrain ischemia and that treatment with HGF suppressed this
      reduction. The expression of Cu/ZnSOD and MnSOD in the hippocampal CA1 region did
      not change after ischemia, regardless of treatment with or not with HGF. The
      activity of NADPH oxidase was increased mainly in glia-like cells in the
      hippocampal CA1 region after ischemia, and this increase was attenuated by HGF
      treatment. These results suggest that the protective effects of HGF against
      cerebral ischemia-induced cell death in the hippocampal CA1 region are related to
      the improvement of neuronal APE/Ref-1 expression and the inhibition of NADPH
      oxidase activity in glia-like cells.

PMID- 16973283
TI  - Ultrasonographic screening for cystic echinococcosis in sheep in Tunisia.
AB  - Sheep from the areas of Fondouk-Jeddid, Bir Mchergua and El Fahs, located in the
      Northeast of Tunisia, were examined by ultrasonography between 2001 and 2004 in
      order to assess their infection with Echinococcus granulosus, the agent of
      hydatid disease, and to evaluate this method as an efficient aire for hydatid
      cysts. A total of 1039 sheep, aged between 1 and 14 years was examined. The
      highest prevalence was found in sheep aged more than 8 years. The least infected
      animals were aged between 1 and 2 years. All hydatid cysts detected by ultrasound
      were located in the liver. In all age-groups, the dead cysts were more numerous
      than viable cysts. Eighteen positive sheep were autopsied and a comparison
      between ultrasound and autopsy results was performed. The results showed a
      prevalence of about 40% for the three areas. Ultrasonography allowed the cysts,
      deep or superficial to localize in the central or left part in relation to the
      caudal vena cava of the animals. Consequently, all the cysts were not detected
      with this technique. This work shows that ultrasonography confirms the importance
      of ovine hydatid cyst in Tunisia and that its use as a mass screening approach
      for cystic echinococcosis in sheep could be helpful for the monitoring of this
      disease in a hydatid control program without great stress for the animals.

PMID- 16973284
TI  - Development of loop-mediated isothermal amplification (LAMP) method for diagnosis
      of equine piroplasmosis.
AB  - Loop-mediated isothermal amplification (LAMP) is a novel nucleic acid method
      whereby DNA is amplified with high specificity, efficiency, and rapidity under
      isothermal conditions using a set of four specifically designed primers and a DNA
      polymerase with strand displacement activity. In this study, we used LAMP primer
      sets designed from EMA-1 and Bc 48 genes for detection of Theileria equi and
      Babesia caballi infections, respectively. These primer sets specifically
      amplified DNA of the respective parasites. Both primer sets amplified T. equi and
      B. caballi up to 10(-6) dilution of 10-fold serially diluted samples.
      Furthermore, DNA extracted from blood collected from a horse experimentally
      infected with T. equi was amplified by a T. equi LAMP primer set from days 2 to
      35 post-infection, demonstrating the high sensitivity of these primers. Of 55
      samples collected from China, 81.8% and 56.3% were positively detected by LAMP
      for T. equi and B. caballi infections, respectively. In contrast, 91.8% and 45.9%
      of the 37 samples collected from South Africa were LAMP positive for T. equi and
      B. caballi, respectively. These results suggest that LAMP could be a potential
      diagnostic tool for epidemiological studies of equine piroplasmosis.

PMID- 16973285
TI  - A survey of Taenia multiceps coenurosis in Sardinian sheep.
AB  - A survey was carried out to assess the occurrence of Coenurus cerebralis
      infection in Sardinian sheep. A prevalence of 0.35% was observed when 566
      regularly slaughtered sheep were examined. However, in 120 sheep with suspected
      symptoms of coenurosis examined from November 2001 to October 2002, a total of
      299 cerebral coenurosis lesions were observed with an incidence of 1% per year.
      Lesions were classified as migratory, cystic and secondary. Most migratory
      lesions were found in sheep aged 3-6 months. Cavitary lesions containing cysts in
      different developing stages were found with high incidence per year in sheep aged
      7-12 months. Secondary lesions due to the development of Coenurus were most
      frequent in sheep aged 19-36 months. Most sheep were found infected in spring and
      in early summer, between March and June. Most lesions were located in the cortex.
      The mean number of protoscolices per cyst was 149 (range 10-370).

PMID- 16973286
TI  - Sporotrichosis: the main differential diagnosis with tegumentary leishmaniosis in
      dogs from Rio de Janeiro, Brazil.
AB  - Seventy-four dogs from the State of Rio de Janeiro with ulcerated cutaneous
      lesions were submitted to clinical, dermatological, parasitological, mycological,
      histopathological and cytopathological exams, a leishmanin skin test, an indirect
      immunofluorescence (IIF) test for leishmaniosis, and nonspecific laboratory tests
      such as blood count and serum biochemistry. Sporothrix schenckii was isolated
      from 41 dogs and Leishmania (Viannia) braziliensis was isolated from 33 animals.
      Most dogs with sporotrichosis were from the municipality of Rio de Janeiro
      (53.7%) and presented ulcerated cutaneous lesions on the head (68.3%). Laboratory
      alterations in these animals included anemia (58.5%), hypoalbuminemia (83%) and
      hyperglobulinemia (75.6%). Histopathology revealed the predominance of a chronic
      granulomatous inflammatory infiltrate (70.7%), and yeast-like structures were
      detected in 17% of the histopathological exams and in 32% of the cytological
      exams. Three of 41 dogs with sporotrichosis were seropositive by IIF for
      leishmaniosis and 2 of 20 animals tested within this group had a positive
      leishmanin skin test. Similarly, most of the 33 dogs with leishmaniosis were from
      the municipality of Rio de Janeiro (69.7%) and had ulcerated cutaneous lesions on
      the head (84.8%). Laboratory alterations in these animals included anemia
      (66.7%), hypoalbuminemia (100%) and hyperglobulinemia (91%). Histopathology
      showed the predominance of a chronic granulomatous inflammatory infiltrate
      (63.6%) and amastigote forms were detected in 30.3% of the histopathological
      exams and in 31.8% of the 22 cytological exams performed. About 72.7% of the dogs
      were seropositive by IIF and five of seven animals had a positive skin test. Due
      to the clinical similarities, histopathological and nonspecific laboratory
      results similarities, the serological and skin tests for leishmaniosis positive
      in dogs with sporotrichosis, and the overlapping endemic areas in Rio de Janeiro,
      the differential diagnosis between the two diseases requires the demonstration of
      their respective etiological agents.

PMID- 16973287
TI  - Evaluation of serological tests for the diagnosis of Neospora caninum infection
      in dogs: optimization of cut off titers and inhibition studies of cross
      reactivity with Toxoplasma gondii.
AB  - Diagnosis of Neospora caninum infection in dogs is based on serological assays
      such as the indirect fluorescent antibody test (IFAT) and enzyme-linked
      immunosorbent assays (ELISA). This study evaluated two serological tests (IFAT
      and ELISA) for the detection of IgG antibodies to N. caninum in 300 serum samples
      of dogs through the optimization of cut off titers by using the two-graph
      receiver-operating characteristic (TG-ROC) curve. In addition, the identification
      of major cross-reactive antigens with Toxoplasma gondii was investigated by
      inhibition ELISA and immunoblotting (IB) assays. IFAT and ELISA results showed
      74% agreement, with a good negative concordance (P(neg)=0.83), but a poor
      positive concordance (P(pos)=0.42). The great majority (86%) of sera with
      positive concordant results (IFAT+/ELISA+) recognized at least two out of three
      N. caninum immunodominant antigens, particularly the 29-32 and 35-37 kDa bands.
      Optimization of cut off titers in IFAT and ELISA was performed considering the
      reactivity to at least two out of three N. caninum immunodominant antigens as
      infection markers, obtaining a titer of 50 for IFAT and 200 for ELISA.
      Seropositivity to N. caninum was significantly associated with T. gondii
      seropositive samples, particularly in ELISA (55.4%). Inhibition ELISA curves for
      N. caninum showed a partial heterologous inhibition, indicating some degree of
      cross-reactivity between N. caninum and T. gondii antigens. Inhibition IB assays
      showed a moderate heterologous inhibition for N. caninum antigens above 45-50
      kDa. These results indicate that ELISA should be used critically when crude
      tachyzoite antigen preparations are employed, due to possible cross-reactivity
      with other related parasites as T. gondii. Also, the cut off dilution of 1:50 in
      IFAT showed to be the most appropriated for N. caninum serology in dogs.
      Therefore, we suggest that N. caninum immunodominant antigens, specially the 17
      and 29-32 kDa proteins, should be selected markers in serological assays for
      canine neosporosis.

PMID- 16973288
TI  - Classification of the parenchymal cells in Fasciola gigantica based on
      ultrastructure and their expression of fatty acid binding proteins (FABPs).
AB  - Parenchymal cells in adult Fasciola gigantica can be classified into three types
      based on their ultrastructural features and different quantities of fatty acid
      binding protein (FABP) being stored. Parenchymal cell type 1 (Pc1) has pale
      cytoplasm consisting largely of a loose network of fine fibers, and it contains
      few mitochondria but numerous glycogen particles. This cell type may be
      specialized in the storage and metabolism of glycogen and glucose. Parenchymal
      cell type 2 (Pc2) has similar cytoplasmic features as Pc1 but contains more
      numerous mitochondria, and high concentration of FABP as reflected by high
      density of immunostaining and immunogold labeling using specific monoclonal
      antibody (MoAb) to FABP as probe. Pc2 may, thus, specialize in the storage and
      metabolism of fatty acids and other lipids. Parenchymal cell type 3 (Pc3) has
      dense cytoplasm containing large amount of rough endoplasmic reticulum, Golgi
      complex and mitochondria, which is typical of a secretory cell. Furthermore, Pc3
      has very little glycogen particles and is not stained by MoAb against FABP. It
      could, thus, be concerned with the synthesis of fibers, which form the scaffold
      of the parenchyma.

PMID- 16973289
TI  - Drug resistance, predictive markers and pharmacogenomics in colorectal cancer.
AB  - Resistance to chemotherapy limits the effectiveness of current cancer therapies,
      including those used to treat colorectal cancer, which is the second most common
      cause of cancer death in Europe and the United States. 5-Fluorouracil-based
      chemotherapy regimens are the standard treatment for colorectal cancer in both
      the adjuvant and advanced disease settings. Drug resistance is thought to cause
      treatment failure in over 90% of patients with metastatic cancer, while drug
      resistant micrometastic tumour cells may also reduce the impact of adjuvant
      chemotherapy treatment. The identification of panels of biomarkers that not only
      identify those patients most likely to benefit from chemotherapy treatment, but
      also which chemotherapies to use, would be a major advance. In this review, we
      describe molecular mechanisms of drug resistance that may be relevant to
      colorectal cancer. We also describe the results of predictive biomarker studies
      in this disease. Finally, we discuss how pharmacogenomics and other high through
      put technologies may impact on the clinical management of colorectal cancer in
      the future.

PMID- 16973290
TI  - Central axis flap methods.
AB  - Extensively burned patients often lack ample healthy skin for
      autotransplantation. Scar contractures are then frequent. Here, we reconstructed
      contractures using flaps of remaining healthy skin around the recipient sites. In
      this report, we present four original scar contracture repair methods using
      subcutaneous pedicled flaps: (1) Propeller flap, (2) multilobed propeller flap,
      (3) scar-band rotation flap and (4) pin-wheel flap. The subcutaneous pedicle
      under the center of these various types of flaps allows these methods to be
      characterized as "central axis flap methods." We have employed these flaps to
      treat mild scar contractures in the axilla and cubital fossa. These methods are
      easily manipulated to restore function and improve aesthetics of scar
      contractures.

PMID- 16973291
TI  - Bangers, burgers and burns. A 10-year review of barbeque burns in South Wales.
AB  - This is a retrospective study of the epidemiology of barbeque burns presenting to
      the Welsh Centre for burns from January 1994 to December 2004. A total of 68 were
      treated of which 57 are included in this study 25% are in the paediatric age
      group. The epidemiology varies between adults and paediatrics. Males are the most
      commonly injured in both groups. The paediatric group have a different aetiology
      compared with the adult group. All paediatric barbeque burns were caused by
      direct contact with either the barbeque or hot sand. This compares to the adult
      group, where 51% were caused by flash burns and only 40% were contact burns.
      Sixty-one percent of the paediatric group were burnt from low lying disposable
      barbeques compared to only 5% of adults. The hands were the most common sites of
      burn for adults (28%) compared to the feet in the paediatric group (36%).
      Barbeque burns in children seem to be increasing in the United Kingdom and we
      suspect that disposable barbeques are the causal factor as they are readily
      available, low-lying and cheap. We suggest preventative measures for such burns.

PMID- 16973292
TI  - Phosphorylation of extracellular signal-related protein kinase is required for
      rapid facilitation of heat-induced currents in rat dorsal root ganglion neurons.
AB  - A subgroup of dorsal root ganglion (DRG) neurons responds to noxious heat with an
      influx of cations carried by specific ion channels such as the transient receptor
      potential channel of the vanilloid receptor type, subtype 1 (TRPV1). Application
      of capsaicin induces a reversible facilitation of these currents. This
      facilitation could be an interaction of two agonists at their common receptor or
      be caused by an influx of calcium ions into the cell. Calcium influx into the
      cell can activate protein kinases such as the extracellular signal-related
      protein kinase (ERK) pathway. This study explored the kinetics, calcium
      dependency and intracellular signals following application of capsaicin and
      leading to facilitation of heat-induced currents (Iheat) in rat DRG neurons.
      Application of 0.5 microM capsaicin caused a 2.65-fold increase of Iheat within 2
      s, which was significantly correlated to a small capsaicin-induced current.
      Intracellular application of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic
      acid (BAPTA), a fast calcium chelator, did not change capsaicin-induced currents
      or Iheat itself, but inhibited facilitation of Iheat by capsaicin. ERK is
      activated by calcium influx and membrane depolarization via the mitogen-activated
      protein kinase/extracellular signal-related protein kinase kinase (MEK).
      Application of the MEK inhibitor U0126 also inhibited facilitation of Iheat by
      capsaicin. We conclude that the MEK/ERK cascade is an intracellular signaling
      pathway playing a vital role in the regulation of nociceptive neurons'
      sensitivity. The very fast kinetics (less than two seconds) are only explainable
      with a membrane-attached or at least membrane-near localization of these kinases.

PMID- 16973293
TI  - Distinct expression pattern of microtubule-associated protein/microtubule
      affinity-regulating kinase 4 in differentiated neurons.
AB  - Protein kinases of the microtubule affinity-regulating kinase (MARK) family were
      originally discovered because of their ability to phosphorylate tau protein and
      related microtubule-associated proteins (MAPs), and their role in the
      establishment of cell polarity in different contexts. Recent papers have
      indicated that microtubule affinity-regulating kinase 4 (MARK4) is a gene that is
      finely regulated at transcriptional level and expressed in two spliced isoforms
      called MARK4L and MARK4S. We here describe the characterization of the mouse
      orthologue of the human MARK4 gene. Interestingly, MARK4S is predominantly
      expressed in the brain, whereas MARK4L shows lower transcript levels in this
      organ. Using MARK4 antibodies specific for each isoform, we found that both
      isoforms have an identical expression pattern in the mouse CNS, and are present
      in a number of neuronal populations. We also found that human microtubule
      affinity-regulating kinase 4S (hMARK4S), whose expression is not detectable in
      human neural progenitor cells (HNPCs) and NTera2 (NT2) cells, is up-regulated in
      both cell systems from the very early stages of neuronal differentiation. This
      indicates that neuronal commitment is marked by MARK4S up-regulation. In
      conclusion, this study provides the first direct evidence suggesting that MARK4
      is a neuron-specific marker in the CNS, and the up-regulation of MARK4S during
      neuronal differentiation suggests that it plays a specialized role in neurons.

PMID- 16973294
TI  - Regionalized cadherin-7 expression by radial glia is regulated by Shh and Pax7
      during chicken spinal cord development.
AB  - During development, several genes that specify neuronal subtype identity are
      expressed in distinct dorsoventral domains of the spinal cord and hindbrain.
      Cadherin-7 (Cad7), a member of the cadherin family of adhesion molecules, is
      expressed by radial glia in a dorsal domain of the spinal cord basal plate in
      chicken. To study the regulation of the Cad7 gene, we ectopically expressed two
      known dorsoventral patterning genes, Shh and Pax7, in the caudal neural tube and
      in two brain regions at different stages of development by in vivo
      electroporation. Results showed that Shh regulated the expression of Cad7 by
      radial glia in a concentration-dependent manner. Shh induced or repressed the
      expression of Cad7, at low and high concentrations, respectively. Furthermore,
      Pax7 inhibited the expression of Cad7. These results are compatible with a role
      of Shh and Pax7 in regulating endogenous Cad7 expression during spinal cord and
      hindbrain development. Our data show, for the first time, that Shh can regulate
      the expression not only of other gene regulatory factors, but also of Cad7, a
      morphoregulatory molecule that plays a role in axon elongation and neural circuit
      formation.

PMID- 16973295
TI  - Transition of mouse de novo methyltransferases expression from Dnmt3b to Dnmt3a
      during neural progenitor cell development.
AB  - Dnmt3a and Dnmt3b, which are known as functional de novo methyltransferases, are
      responsible for creating genomic methylation patterns during mammalian
      development. Recently, we have shown that specific expression of Dnmt3b in
      epiblast, embryonic ectoderm, hematopoietic progenitor cells and spermatogonia
      cells is followed by Dnmt3a expression (Watanabe D, Suetake I, Tada T, Tajima S
      (2002) Stage- and cell-specific expression of Dnmt3a and Dnmt3b during
      embryogenesis. Mech Dev 118:187-190; Watanabe D, Suetake I, Tajima S, Hanaoka K
      (2004) Expression of Dnmt3b in mouse hematopoietic progenitor cells and
      spermatogonia at specific stages. Gene Expr Patterns 5:43-49). In this study, we
      analyzed the expression of mouse de novo methyltransferases during development of
      the nervous systems. In the embryonic olfactory epithelium (OE), Dnmt3b was
      specifically expressed in Mash1 positive globose basal cells (i.e. transiently
      amplifying neural progenitor cells), while Dnmt3a was expressed in immature
      olfactory receptor neurons. Dnmt3b-positive cells were rarely observed in the
      adult OE, but were increased in regenerating OE with intranasal ZnSO(4)
      administration. Dnmt3b was also detected in the E8.5 neural plate, E10.5 spinal
      cord and retina cells, while Dnmt3a was expressed in postmitotic young neurons.
      Furthermore, Dnmt3b was specifically expressed in ES cells, while Dnmt3a was
      transiently expressed during neural cell differentiation of ES cells. Dnmt3b is
      specifically expressed in progenitor cells during hematopoiesis, spermatogenesis
      and neurogenesis, suggesting an important role in the initial steps of progenitor
      cell differentiation. Dnmt3a is expressed in postmitotic young neurons following
      the Dnmt3b expression. Dnmt3a may be required for the establishment of tissue
      specific methylation patterns of the genome. The coordinated expression of de
      novo methyltransferases from Dnmt3b to Dnmt3a suggests conserved mechanisms of de
      novo methylation of the genome and different functions for Dnmt3b and Dnmt3a
      during progenitor cell development.

PMID- 16973296
TI  - Subthalamic nucleus neurones in slices from 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine-lesioned mice show irregular, dopamine-reversible firing
      pattern changes, but without synchronous activity.
AB  - The loss of dopamine in idiopathic or animal models of Parkinson's disease
      induces synchronized low-frequency oscillatory burst-firing in subthalamic
      nucleus neurones. We sought to establish whether these firing patterns observed
      in vivo were preserved in slices taken from dopamine-depleted animals, thus
      establishing a role for the isolated subthalamic-globus pallidus complex in
      generating the pathological activity. Mice treated with 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) showed significant reductions of over 90% in levels of
      dopamine as measured in striatum by high pressure liquid chromatography.
      Likewise, significant reductions in tyrosine hydroxylase immunostaining within
      the striatum (>90%) and tyrosine hydroxylase positive cell numbers (65%) in
      substantia nigra were observed. Compared with slices from intact mice, neurones
      in slices from MPTP-lesioned mice fired significantly more slowly (mean rate of
      4.2 Hz, cf. 7.2 Hz in control) and more irregularly (mean coefficient of
      variation of inter-spike interval of 94.4%, cf. 37.9% in control). Application of
      ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione
      (CNQX) and 2-amino-5-phosphonopentanoic acid (AP5) and the GABA(A) receptor
      antagonist picrotoxin caused no change in firing pattern. Bath application of
      dopamine significantly increased cell firing rate and regularized the pattern of
      activity in cells from slices from both MPTP-treated and control animals.
      Although the absolute change was more modest in control slices, the maximum
      dopamine effect in the two groups was comparable. Indeed, when taking into
      account the basal firing rate, no differences in the sensitivity to dopamine were
      observed between these two cohorts. Furthermore, pairs of subthalamic nucleus
      cells showed no correlated activity in slices from either control (21 pairs) or
      MPTP-treated animals (20 pairs). These results indicate that the isolated but
      interconnected subthalamic-globus pallidus network is not itself sufficient to
      generate the aberrant firing patterns in dopamine-depleted animals. More likely,
      inputs from other regions, such as the cortex, are needed to generate
      pathological oscillatory activity.

PMID- 16973297
TI  - Peri-pubertal maturation after developmental disturbance: a model for psychosis
      onset in the rat.
AB  - Schizophrenia is thought to be associated with abnormalities during
      neurodevelopment although those disturbances usually remain silent until puberty;
      suggesting that postnatal brain maturation precipitates the emergence of
      psychosis. In an attempt to model neurodevelopmental defects in the rat, brain
      cellular proliferation was briefly interrupted with methylazoxymethanol (MAM)
      during late gestation at embryonic day 17 (E17). The litters were explored at pre
      and post-puberty and compared with E17 saline-injected rats. We measured
      spontaneous and provoked locomotion, working memory test, social interaction, and
      prepulse inhibition (PPI). As compared with the saline-exposed rats, the E17 MAM
      exposed rats exhibited spontaneous hyperactivity that emerged only after puberty.
      At adulthood, they also exhibited hypersensitivity to the locomotor activating
      effects of a mild stress and a glutamatergic N-methyl-D-aspartate receptor
      antagonist (MK-801), as well as PPI deficits whereas before puberty no
      perturbations were observed. In addition, spatial working memory did not undergo
      the normal peri-pubertal maturation seen in the sham rats. Social interaction
      deficits were observed in MAM rats, at both pre- and post-puberty. Our study
      further confirms that transient prenatal disruption of neurogenesis by MAM at E17
      is a valid behavioral model for schizophrenia as it is able to reproduce some
      fundamental features of schizophrenia with respect to both phenomenology and
      temporal pattern of the onset of symptoms and deficits.

PMID- 16973298
TI  - Antiphasic Purkinje cell responses in mouse uvula-nodulus are sensitive to static
      roll-tilt and topographically organized.
AB  - Two vestibular pathways converge at the uvula-nodulus to modulate the discharge
      of Purkinje cell complex and simple spikes (CSs and SSs). In the mouse,
      vestibular primary afferent mossy fibers originate from each of the end organs of
      the ipsilateral labyrinth and terminate in the granule cell layers of folia 9c
      10. Vestibular climbing fiber projections originate from the contralateral beta
      nucleus and dorsomedial cell column (dmcc) and terminate directly on Purkinje
      cells. CSs and SSs could be regulated independently or they could be co
      dependent. Here we examine how the discharges of CSs and SSs are modulated by
      sinusoidal and static roll-tilt in the uvula-nodulus of mice anesthetized with
      either chloralose-urethane or ketamine-xylazine. All vestibularly-driven CSs and
      SSs were sensitive to static roll-tilt. None were sensitive to horizontal
      vestibular stimulation. CSs were modulated in phase with ipsilateral roll-tilt.
      SSs were modulated out of phase. Spontaneous discharges of CSs were followed by a
      pause in SSs. Phase leads of CSs and SSs with respect to sinusoidal roll-tilt
      were advanced by ketamine-xylazine anesthesia relative to chloralose-urethane
      anesthesia by approximately 45 degrees. The antiphasic modulation of CSs and SSs
      was independent of anesthetic. Chloralose-urethane, but not ketamine-xylazine,
      induced spontaneous oscillations of CSs and SSs in 16% of Purkinje cells. Optimal
      planes of CSs in folia 9c-10 Purkinje cells were organized topographically into
      sagittal zones whose widths were approximately 400 microm. Purkinje cells with
      optimal planes in the posterior quadrant of the ipsilateral hemi-field were
      located in a medial zone. Purkinje cells with optimal planes in the anterior
      quadrant of the ipsilateral hemi-field were located in a lateral zone. The CS
      associated pause in SSs establishes a vector-specific SS output. The amplitude of
      SS modulation may depend on parallel fiber-mediated signals to Purkinje cells as
      well as on the state of cerebellar interneurons.

PMID- 16973299
TI  - Ischemic preconditioning negatively regulates plenty of SH3s-mixed lineage kinase
      3-Rac1 complex and c-Jun N-terminal kinase 3 signaling via activation of Akt.
AB  - Activation of Akt/protein kinase B has been recently reported to play an
      important role in ischemic tolerance. We here demonstrate that the decreased
      protein expression and phosphorylation of phosphatase and tensin homolog deleted
      from chromosome 10 (PTEN) underlie the increased Akt-Ser-473 phosphorylation in
      the hippocampal CA1 subfield in ischemic preconditioning (IPC). Co
      immunoprecipitation analysis reveals that Akt physically interacts with Rac1, a
      small Rho family GTPase required for mixed lineage kinase 3 (MLK3)
      autophosphorylation, and both this interaction and Rac1-Ser-71 phosphorylation
      induced by Akt are promoted in preconditioned rats. In addition, we show that Akt
      activation results in the disassembly of the plenty of SH3s (POSH)-MLK3-Rac1
      signaling complex and down-regulation of the activation of MLK3/c-Jun N-terminal
      kinase (JNK) pathway. Akt activation results in decreased serine phosphorylation
      of 14-3-3, a cytoplasmic anchor of Bax, and prevents ischemia-induced
      mitochondrial translocation of Bax, release of cytochrome c, and activation of
      caspase-3. The expression of Fas ligand is also decreased in the CA1 region. Akt
      activation protects against apoptotic neuronal death as shown in TUNEL staining
      following IPC. Intracerebral infusion of LY294002 before IPC reverses the
      increase in Akt phosphorylation and the decrease in JNK signaling activation, as
      well as the neuroprotective action of IPC. Our results suggest that activation of
      pro-apoptotic MLK3/JNK3 cascade can be suppressed through activating anti
      apoptotic phosphoinositide 3-kinase/Akt pathway induced by a sublethal ischemic
      insult, which provides a functional link between Akt and the JNK family of stress
      activated kinases in ischemic tolerance.

PMID- 16973300
TI  - Altered distribution and levels of cathepsinD and cystatins in amyotrophic
      lateral sclerosis transgenic mice: possible roles in motor neuron survival.
AB  - In amyotrophic lateral sclerosis (ALS) there is a selective degeneration of motor
      neurons leading to muscle paralysis and death. The mechanism underlying cell
      demise in ALS is not fully understood, but involves the activation of different
      proteolytic enzymes, including the caspase family of cysteine proteases. We have
      here studied whether other proteases, such as the cathepsins, residing in
      lysosomes, and the cathepsin inhibitors, cystatinB and -C are changed in ALS. The
      expression and protein levels of the cathepsinB, -L and -D all increased in the
      spinal cord in ALS mice, carrying the mutant copper/zinc superoxide dismutase
      (SOD1) gene. At the cellular level, cathepsinB and -L were present in ventral
      motor neurons in controls, but in the ALS mice cathepsinB was also expressed by
      glial fibrillary acidic protein (GFAP) positive astrocytes. The distribution of
      the aspartic protease, cathepsinD also changed in ALS with a loss of the
      lysosomal staining in motor neurons. Inhibition of caspases by means of X
      chromosome-linked inhibitor of apoptosis protein (XIAP) overexpression did not
      inhibit cleavage of cathepsinD in ALS mice, suggesting a caspase-independent
      pathway. Expression of cystatinB and -C increased slightly in the ALS spinal
      cords. Immunostaining showed that in ALS, cystatinC was present in motor neurons
      and in GFAP positive astrocytes. CystatinB that is a neuroprotective factor
      decreased in motor neurons in ALS but was expressed by activated microglial
      cells. The observed changes in the levels and distributions of cathepsinD and
      cystatinB and-C indicate a role of these proteins in the degeneration of motor
      neurons in ALS.

PMID- 16973301
TI  - Changing Pax6 expression correlates with axon outgrowth and restoration of
      topography during optic nerve regeneration.
AB  - Pax6, a member of the highly conserved developmental Pax gene family, plays a
      crucial role in early eye development and continues to be expressed in adult
      retinal ganglion cells (RGCs). Here we have used Western blots and
      immunohistochemistry to investigate the expression of Pax6 in the formation and
      refinement of topographic projections during optic nerve regeneration in
      zebrafish and lizard. In zebrafish with natural (12-h light/dark cycle)
      illumination, Pax6 expression in RGCs was decreased during axon outgrowth and
      increased during the restoration of the retinotectal map. Rearing fish in
      stroboscopic illumination to prevent retinotopic refinement resulted in a
      prolonged decrease in Pax6 levels; return to natural light conditions resulted in
      map refinement and restoration of normal Pax6 levels. In lizard, RGC axons
      spontaneously regenerate but remain in a persistent state of regrowth and do not
      restore topography; visual training during regeneration, however, allows a
      stabilization of connections and return of topography. Pax6 was persistently
      decreased in untrained animals but remained increased in trained ones. In both
      species, changes in expression were not due to cell division or cell death. The
      results suggest that decreased Pax6 expression is permissive for axon
      regeneration and extensive searching, while higher levels of Pax6 are associated
      with restoration of topography.

PMID- 16973302
TI  - Involvement of medial prefrontal cortex neurons in behavioral and cardiovascular
      responses to contextual fear conditioning.
AB  - To explore the ventral medial prefrontal cortex (vMPFC) involvement in behavioral
      and autonomic fear-conditioned responses to context, vMPFC synaptic transmission
      was temporarily inhibited by bilateral microinjections of 200 nL of the
      nonselective synapse blocker CoCl(2) (1 mM). Behavioral activity (freezing, motor
      activity and rearing) as well as evoked cardiovascular responses (arterial
      pressure and heart rate) was analyzed. Rats were pre-exposed to the footshock
      chamber (context) and shock stimulus was used unconditioned stimulus. During re
      exposure to context, conditioned rats spent 80% of the session in freezing while
      non-conditioned rats (no shock group) spent less than 15% of the session time in
      freezing. Conditioned rats had significantly lower activity scores than non
      conditioned animals. Exposure to context increased mean arterial pressure (MAP)
      and heart rate (HR) of both groups. MAP and HR of the conditioned animals were
      markedly increased and remained at a high and stable level, whereas MAP and HR
      increases in non-conditioned animals were less pronounced and declined during the
      session. CoCl(2) microinjected in the vMPFC significantly reduced freezing and
      attenuated MAP and HR increase of the conditioned group. Cobalt-induced vMPFC
      inhibition also significantly reduced MAP and HR increase observed in non
      conditioned animals, without any behavioral changes. The effect of vMPFC acute
      ablation on MAP and HR did not seem to be specific to the fear response because
      they were also evident in non-conditioned animals. The results indicate that
      vMPFC integrity is crucial for expression of fear-conditioned responses to
      context, such as freezing and cardiovascular changes, suggesting that fear
      conditioned responses to context involve cortical processing prior to amygdalar
      output. They also indicate a cardiovascular response observed during re-exposure
      of non-conditioned rats to the context is completely dependent on vMPFC
      integrity.

PMID- 16973303
TI  - Adjuvant radiotherapy for cutaneous melanoma: comparing hypofractionation to
      conventional fractionation.
AB  - PURPOSE: To examine locoregional control after adjuvant radiotherapy (RT) for
      cutaneous melanoma and compare outcomes between conventional fractionation and
      hypofractionation. METHODS AND MATERIALS: Between January 1980 and June 2004, 56
      patients with high-risk disease were treated with adjuvant RT. Indications for RT
      included: recurrent disease, cervical lymph node involvement, lymph nodes >3 cm,
      more than three lymph nodes involved, extracapsular extension, gross residual
      disease, close or positive margins, or satellitosis. Hypofractionation was used
      in 41 patients (73%) and conventional fractionation was used in 15 patients
      (27%). RESULTS: The median age was 61 years (21->90). The median follow-up among
      living patients was 4.4 years (range, 0.6-14.4 years). The primary site was
      located in the head and neck in 49 patients (87%) and below the clavicles in 7
      patients (13%). There were 7 in-field locoregional failures (12%), 3 out-of-field
      regional failures (5%), and 24 (43%) distant failures. The 5-year in-field
      locoregional control (ifLRC) and freedom from distant metastases (FFDM) rates
      were 87% and 43%, respectively. The 5-year cause-specific (CSS) and overall
      survival (OS) was 57% and 46%, respectively. The only factor associated with
      ifLRC was satellitosis (p = 0.0002). Nodal involvement was the only factor
      associated with FFDM (p = 0.0007), CSS (p = 0.0065), and OS (p = 0.016). Two
      patients (4%) who experienced severe late complications, osteoradionecrosis of
      the temporal bone and radiation plexopathy, and both received hypofractionation
      (5%). CONCLUSIONS: Although surgery and adjuvant RT provides excellent
      locoregional control, distant metastases remain the major cause of mortality.
      Hypofractionation and conventional fractionation are equally efficacious.

PMID- 16973304
TI  - The pleiotropic Arabidopsis frd mutation with altered coordination of chloroplast
      biogenesis, cell size and differentiation, organ size and number.
AB  - In higher plants, plastid development must be tightly coordinated with cell and
      organ development. In this paper, a novel T-DNA-mutagenized Arabidopsis line
      showing chlorotic leaves and minute stature was identified in a genetic screen
      for altered chloroplast development. The mutation corresponded to a single locus
      on chromosome IV and was associated with insertion of the T-DNA. This locus was
      named FARFADET and resulted in pleiotropic effects on chloroplast biogenesis,
      cell size and differentiation, organ size and number. Thus, in contrast with
      previously described chlorotic mutants, frd mutants were affected not only in
      chloroplast development and chlorophyll accumulation, but also in cell and organ
      development. Alteration of differentiation affected different cell types such as
      leaf epidermal cells, trichomes, mesophyll cells, and columella cells. A major
      effect on mesophyll cell differentiation was the lack of palisadic parenchyma and
      absence of grana stacks. Moreover, meristem size and lateral meristem initiation
      were affected. Genetic and molecular characterisation showed that the T-DNA
      insertion generated 41 bp deletion in a potential miRNA precursor. The predicted
      miRNA target genes were involved in plant development and stress. It is therefore
      hypothesized that the frd mutation had affected coordination of cell
      developmental span and the control of the division-differentiation balance.

PMID- 16973305
TI  - Structure, expression, and mapping of two nodule-specific genes identified by
      mining public soybean EST databases.
AB  - Numerous nodule-specific genes, which are involved in the root nodule development
      and function, have been known and are still being discovered. Here, we reported
      the structure, expression, and genetic map location of two novel nodule-specific
      genes. First, two EST groups, one obtained from a nodule library and the other
      from all aboveground tissue libraries, were clustered with regard to in silico
      expression profiles. We compiled a pool of 103 putative nodule-specific sequence
      clusters. Then, two representative ESTs were selected for further experimental
      analyses. According to the full-length cDNA sequences, one was an EST of a novel
      nodule-specific polygalacturonase gene, GmPGN, and the other was an EST of a new
      short nodule-specific gene, GmEKN. The results of expression analyses of the
      GmPGN cDNAs indicated that GmPGN expression was not detectable in any of the
      soybean tissues except in the nodule tissue and may be regulated via alternative
      splicing. GmEKN expression was the most strongly detected in the nodule. The
      predicted GmEKN protein is both glutamic acid- and lysine-rich, and is also
      highly hydrophilic. Genetic mapping located GmPGN near the known quantitative
      trait locus conferring resistance to soybean cyst nematode on soybean molecular
      linkage group (MLG) B1, and GmEKN on MLG A2. These results provide useful
      information for the use of these genes in research on the orchestration of
      numerous genes in nodule development and function.

PMID- 16973306
TI  - Multilocus-sequence typing analysis reveals similar populations of Streptococcus
      uberis are responsible for bovine intramammary infections of short and long
      duration.
AB  - Multilocus-sequence typing (MLST) was used to analyse Streptococcus uberis
      isolates from a single herd associated with long duration (50-260 days) and
      rapidly cleared (less than 1 month) bovine intramammary infections to determine
      whether the bacterial type had any impact on the duration of infection. Most
      chronic infections (24 of 33) were due to continuous infection of the mammary
      quarter with the same sequence type, and infections were found to persist for
      many months. The remaining quarters were re-infected with a different sequence
      type within a single lactation. No particular sequence type or clonal complex
      (lineage) was associated with persisting infections, indicating that the outcome
      of intramammary infections with S. uberis is more likely to be dependent on host
      factors than on inter-strain differences. Analysis of these strains alongside
      others obtained from the same herd at a later date revealed the shift in the
      predominant genotypes with time.

PMID- 16973307
TI  - Assessment of serological response of young and adult sheep to conjunctival
      vaccination with Rev-1 vaccine by fluorescence polarization assay (FPA) and other
      serological tests for B. melitensis.
AB  - The serological response of young and adult sheep vaccinated conjunctivally with
      Rev-1 vaccine was assessed by fluorescence polarization assay (FPA), Rose Bengal
      test (RBT), complement fixation test (CFT), modified Rose Bengal test (m-RBT),
      indirect ELISA (i-ELISA) and competitive ELISA (c-ELISA), at different post
      vaccination intervals. One hundred and thirty six adult sheep and 64 lambs were
      used in the study. The vaccinated animals were bled prior to vaccination (0 day)
      and thereafter at 21st, 42nd, 35th, 63rd, 91st, 125th, 159th, and 223rd and 330th
      day post vaccination. The majority of animals (young and adult) showed positive
      reaction by FPA, RBT, CFT, m-RBT and c-ELISA 21 days post vaccination, whereas by
      i-ELISA at 42 days. All tests perform equal when animals vaccinated as young are
      tested 125 days (4 months) post vaccination. In case of animals vaccinated at
      adulthood, FPA, RBT, CFT and c-ELISA perform equal if the animals are tested 223
      days (approximately 8 months) post vaccination. I-ELISA and m-RBT show low
      specificity if ewes vaccinated at adulthood are tested 330 days (11 months) post
      vaccination. If control of brucellosis in sheep is based on conjunctivally
      vaccination of lambs with Rev-1, the vaccinated animals can be tested by any test
      used for diagnosis of B.melitensis infection accurately at least 4 months post
      vaccination. If brucellosis control is based on mass vaccination the use of m-RBT
      and i-ELISA is not recommended for testing adult animals at least for 330 days
      (11 months) post vaccination due to tests low specificity. Further research is
      needed so the appropriate cut-offs to be established for FPA, c-ELISA or i-ELISA
      to become valuable tools for the eradication of Brucella spp. infection in small
      ruminants in areas where vaccination is practiced.

PMID- 16973308
TI  - ESBL- and plasmidic class C beta-lactamase-producing E. coli strains isolated
      from poultry, pig and rabbit farms.
AB  - This study aims to determine the presence of extended-spectrum (ESBL) and
      plasmidic class C beta-lactamase-producing Enterobacteriaceae in poultry, pig and
      rabbit farms of Catalonia (Spain). PFGE typing showed a low clonal relationship
      among strains carrying these mechanisms of resistance. Ninety-three percent of
      them were resistant to two or more of the non-beta-lactam antimicrobials tested
      and harboured ESBL and plasmidic class C beta-lactamases. Greater diversity of
      these enzymes was found in strains from poultry farms, the CTX-M-9 family,
      especially CTX-M-14, with CMY-2 being the most frequent. The isolation of TEM-52
      and SHV-2-producing Escherichia coli strains from these animal farms is
      noteworthy. In contrast, 73% of the strains from pig farms had CTX-M-1, and
      neither the CMY-type nor CTX-M-9 family enzyme was found. Likewise, it is the
      first time that CTX-M-1 and SHV-5 encoding strains have been isolated in pigs. On
      the other hand, in rabbit farms CTX-M-9 family was also the most frequent, being
      detected in three of a total of four strains. The last one showed a CMY-2, for
      the first time detected in these animals, too. In conclusion, commensal E. coli
      strains of food-producing animal farms are a reservoir of ESBL and plasmidic
      class C beta-lactamases.

PMID- 16973309
TI  - Molecular cloning of a Mycoplasma meleagridis-specific antigenic domain endowed
      with a serodiagnostic potential.
AB  - A recombinant phage library harbouring Mycoplasma meleagridis (MM) genomic DNA
      fragments was generated in the bacteriophage lambda gt11 expression vector. The
      library was screened for expression of MM specific antigens with a polyclonal
      antiserum that had been preadsorbed with antigens of the most common unrelated
      avian mycoplasma species. A 49-amino acid antigenic domain unique to MM was
      isolated, expressed in Escherichia coli, and its serodiagnostic potential was
      demonstrated. An antiserum raised against this MM-specific antigenic domain
      recognized a cluster of seven membrane-associated MM proteins with molecular
      masses ranging from 34 to 75 kDa. Overall, this study resulted in the
      identification of a potent serodiagnostic tool and revealed the complex antigenic
      nature of MM.

PMID- 16973310
TI  - Effects of pre-culture holding time and temperature on interferon-gamma responses
      in whole blood cultures from Mycobacterium bovis-infected cattle.
AB  - The Bovigam assay is approved for use within the United States as a complementary
      tuberculosis test. Prior to whole blood culture and the ensuing ELISA to detect
      interferon-(IFN)-gamma, samples are subjected to various holding time/temperature
      combinations due, in part, to practical constraints associated with shipment of
      samples to approved laboratories. To evaluate these effects, 5-month-old Holstein
      calves (n = 7) received 10(3) cfu Mycobacterium bovis by aerosol. Heparinized
      blood was collected 2 months after challenge and held at 4 or 22 degrees C for 0,
      8 or 24 h prior to culture with mycobacterial antigens or pokeweed mitogen (PWM).
      Responses of samples held for 8 or 24 h were comparable and lower than responses
      of cultures prepared immediately after collection, regardless of holding
      temperature. Differences in responses of samples held at 4 degrees C versus 22
      degrees C were also minimal. A subset of samples was held for 2 h at 37 degrees C
      at the beginning of the holding period. This subset of samples had diminished
      responses to all stimulants and increased holding times (i.e., 24 h versus 8 h)
      negatively impacted the response. Pre-processing conditions, particularly delays
      in set-up and initial high sample temperatures, reduces IFN-gamma responses of
      cells from infected cattle increasing the risk of false negatives in this assay
      of regulatory importance.

PMID- 16973311
TI  - Association of growth in utero with cognitive function at age 6-8 years.
AB  - BACKGROUND: Size at birth is associated with later cognitive development. The
      timing of growth faltering in utero may affect developmental consequences. AIM:
      To determine whether growth in utero is related to cognitive outcomes in
      childhood. A secondary aim was to determine any associations between maternal
      nutritional status and cognition. STUDY DESIGN AND SUBJECTS: Subjects were
      participants in a prospective cohort study of developmental origins of adult
      disease. Eligible subjects were aged 6-8 years at their next scheduled visit to
      the study clinic and their mothers had abdominal ultrasound measurements at 14,
      25 and 35 weeks gestation. 186 of 264 eligible children attended the clinic and
      were tested. OUTCOME MEASURES: Raven's Progressive Matrices (reasoning ability),
      Peabody Picture Vocabulary Test (receptive vocabulary) and Digit Span Forwards
      (auditory working memory). RESULTS: In multiple regression analyses controlling
      for children's age and socioeconomic status, head circumference at 14 weeks
      gestation was significantly associated with reasoning ability. The difference
      between the lowest and highest quartiles was equivalent to 0.4 S.D. No other
      significant associations with fetal growth were found. Maternal weight gain was
      not associated with cognitive scores; however, change in triceps skinfold between
      25 and 35 weeks gestation was positively associated with reasoning ability and
      remained a significant predictor when included in the regression model.
      CONCLUSIONS: There were few associations between growth in utero and cognition.
      Growth in head circumference in early gestation and maternal nutrition in late
      gestation may affect later cognitive ability. Further research in this area is
      needed to confirm these results.

PMID- 16973312
TI  - ACP1 and offspring sex ratio in smoking puerperae: a study at population level.
AB  - BACKGROUND: Data from previous study by our group suggest that in smoking women
      sex ratio of offspring is higher in newborns carrying ACP1C allele than in other
      ACP1 genotypes, suggesting that differences observed among human population
      concerning the effect of smoking may depend in part on this genetic factor.
      OBJECTIVES: In order to further explore this issue we have studied another
      population and have analysed the relationship between sex ratio and ACP1C gene
      frequency at population level. METHODS: The analysis includes 719 consecutive
      births from Central Italy considered in a previous paper and 5510 consecutive
      births from Sardinia. Data from English and Japanese populations have also been
      considered in the analysis. RESULTS: Among newborns not carrying ACP1C there is a
      decrease of SR among the offspring of smoking mothers, while among newborns
      carrying the ACP1C allele there is an increase of SR among the offspring of
      smoking mothers relative to non-smoking mothers. Considering Sardinian, Italian,
      English and Japanese population there is a linear positive relationship between C
      allele frequency and SR in smoking mothers. CONCLUSIONS: The present observation
      suggests an interaction between smoking and ACP1 regarding their effects on sex
      ratio, by which the presence of the ACP1C allele appears to counteract the effect
      of smoking. This suggests that genetic background may modify the effects of toxic
      environmental factors on gamete production and functionality and/or on
      intrauterine survival.

PMID- 16973313
TI  - Clinical aspects of obesity in the gynecological endocrinologicaly practice.
AB  - Obesity is epidemic of 21st century, its visceral form is associated with
      increased risk for type 2 diabetes, cardiovascular disease, hypertension and
      increased mortality due to consequences of the disease. This type of obesity is a
      common diagnostic and therapeutic problem in gynecological practice. This
      especially concerns polycystic ovary disease, in which this type of obesity with
      its metabolic consequences is one of the important factors in etiology and
      additionally may lead to remote metabolic and cardiovascular problems. Another
      group of women in which this type of obesity plays an important role are
      climacteric women in whom redistribution of adipose tissue with increase in
      visceral fat deposit occurs. On the basis of current viewpoints and own
      experiences, the authors propose a diagnostic-therapeutic algorithm in women with
      visceral obesity and polycystic ovary disease or climacteric period. In case with
      cardiovascular risk factors (waist circumference over than 80cm, serum
      triglycerides over 1.7mmol/l, HDL cholesterol lower than 1.0mmol/l, blood
      pressure over 130/85mmHg and fast serum glucose levels over 100mg/dl) the
      therapeutic model focuses on the recognize risk factors. It must be considered
      that diet and physical activity play a very important role in the therapy.

PMID- 16973314
TI  - Formation of self-organized nanoparticles by lecithin/chitosan ionic interaction.
AB  - In this work the production of auto-assembled nanoparticles obtained by the
      mixing of chitosan and lecithin is presented. The size and surface charge of the
      nanoparticles were studied as function of the weight ratio between components,
      the viscosity of the polysaccharide and the pH of the colloidal suspension. In
      order to elucidate the structure of nanoparticles, micro-FT-IR and elastic
      neutron scattering experiments have been performed. Results evidenced a strong
      electrostatic interaction between components and a structure that is neither that
      of homogeneous spheres nor of coated unilamellar vesicles. Preliminary
      encapsulation experiments with progesterone, as model lipophilic drug, showed
      good encapsulation efficiencies.

PMID- 16973315
TI  - Antidepressant therapy in tinnitus.
AB  - OBJECTIVE: Review the literature on the co-morbidity of depression and anxiety
      with tinnitus. Briefly consider proposed mechanisms by which antidepressants
      might be helpful for tinnitus, including treatment of co-morbid depression and
      anxiety and a more direct serotonergic mechanism of tinnitus. Survey the
      literature on antidepressants and tinnitus including tinnitus reported as a side
      effect of antidepressants (phenelzine, amitriptyline, protriptyline, doxepin,
      imipramine, fluoxetine, trazadone, bupropion, venlafaxine), tinnitus associated
      with withdrawal of antidepressants (venlafaxine and sertraline) and
      antidepressants as a treatment for tinnitus (case reports--fluoxetine and
      paroxetine, retrospective reviews--imipramine and selective serotonin reuptake
      inhibitors, single blind trials of amitriptyline and double blind placebo
      controlled trials of trimipramine, nortriptyline, paroxetine and sertraline).
      Provide suggestions on future directions, specifically replication of prior
      studies and a dose finding study of paroxetine for the treatment of tinnitus.

PMID- 16973317
TI  - Asymmetry of masking in the European starling: behavioural auditory thresholds.
AB  - Psychophysical studies of simultaneous masking with human observers exhibit an
      asymmetry in the amount of masking that depends on the relative bandwidths of
      signals and maskers. For noise bands up to the bandwidth of one auditory filter,
      masked auditory thresholds are considerably lower when the bandwidth of the
      signal exceeds that of the masker compared to the reversed condition. We
      investigate asymmetry of masking in an animal model, that will allow to study the
      mechanisms associated with the asymmetry of masking effect. European starlings
      (Sturnus vulgaris) were trained in a Go/NoGo paradigm to report the detection of
      a 500 ms noise signal centred in a 700 ms noise masker. Signals and maskers with
      centre frequencies of 2 kHz had bandwidths of 4 Hz or 256 Hz. Thresholds for
      detecting the 256 Hz wide-band signal in a 4 Hz narrow-band masker were
      considerably lower compared to detecting the 4 Hz narrow-band signal in a 256 Hz
      wide masker and compared to all other conditions. The asymmetry of masking in
      starlings was on average 15 and 17 dB for 40 and 70 dB SPL overall masker level,
      respectively. Our animal model thus proved perceptual abilities similar to human
      subjects. The results are discussed with respect to the importance of both
      intensity and temporal cues for signal detection.

PMID- 16973316
TI  - Effects of exposing gonadectomized and intact C57BL/6J mice to a high-frequency
      augmented acoustic environment: Auditory brainstem response thresholds and
      cytocochleograms.
AB  - Gonadectomized and surgically intact adult C57BL/6J (B6) mice of both sexes were
      exposed for 12h nightly to a high-frequency augmented acoustic environment (AAE):
      repetitive bursts of a half-octave noise band centered at 20 kHz, 70 dB SPL. The
      effects of sex, gonadectomy, and AAE treatment on genetic progressive hearing
      loss (exhibited by B6 mice) were evaluated by obtaining auditory brainstem
      response thresholds at ages 3-, 6-, and 9-months; hair cell counts
      (cytocochleograms) were obtained at 9 months. A sex difference in the rate of
      genetic progressive hearing loss in B6 mice (observed by earlier studies) was
      confirmed, with females exhibiting a faster rate of threshold elevations and more
      severe loss of hair cells at age 9 months. Gonadectomy had no consistent effects
      on the rate or severity of hearing loss in non-exposed mice of either sex. An
      unexpected finding was that the high-frequency AAE treatment caused additional
      ABR threshold elevations and hair cell loss. In an earlier study, the same high
      frequency AAE treatment on DBA/2J mice ameliorated hearing loss. The most severe
      AAE-induced losses occurred in surgically intact females, suggesting a
      potentiating effect of ovarian hormone(s).

PMID- 16973318
TI  - Cytotoxic constituents from Butea superba Roxb.
AB  - A carpin (3-hydroxy-9-methoxypterocarpan) (Medicarpin) (1) and four isoflavones,
      7-hydroxy-4'-methoxy-isoflavone (Formononetin) (2); 7,4'-dimethoxyisoflavone (3);
      5,4'-dihydroxy-7-methoxy-isoflavone (Prunetin) (4) and 7-hydroxy-6,4'
      dimethoxyisoflavone (5) were isolated from the tuber roots of Butea superba Roxb.
      Compounds 2 and 4 showed moderate cytotoxic activity on KB cell lines with IC(50)
      (microM) values of 37.3+/-2.5 and 71.1+/-0.8 and on BC cell lines with IC(50)
      (microM) values of 32.7+/-1.5 and 47.3+/-0.3, respectively.

PMID- 16973319
TI  - Enhancement of learning and memory by a medicinal formulation, Saenhyetang, in
      mice.
AB  - The effects on memory and learning ability of the Korean herbal medicine,
      Saenhyetang (SHT), which is consisted of nine herbs, were investigated. Hot water
      extracts (HWE-SHT) and ethanol extracts (EE-SHT) were used for the studies. It
      was shown that N-methyl-d-aspartate (NMDA) receptor 2B (NR2B) was increased in
      the forebrains of SHT-administrated mice (HWE-SHT), leading to enhanced
      activation of NMDA receptors, facilitating synaptic potentiation in response to
      stimulation at 10-100Hz. These HWE-SHT-treated mice exhibit superior ability in
      learning and memory in various behavioral tasks, showing that NR2B is enhanced by
      HWE-SHT treatment and also is critical in gating the age-dependent threshold for
      plasticity and memory formation. NMDA receptor-dependent modifications, which
      were mediated in part by HWE-SHT administration, of synaptic efficacy, therefore,
      represent a mechanism for associative learning and memory. Results suggest that
      oriental medical enhancement of NR2B attributes such as intelligence and memory
      in mammals is feasible. On the other hand, to examine the effects of EE-SHT on
      the learning and memory in experimental mice, the passive and active avoidance
      responses were studied. The EE-SHT ameliorated the memory retrieval deficit
      induced by ethanol, but not other memory impairment in mice. EE-SHT (10,
      20mg/100g, p.o.) did not affect the passive avoidance responses of normal mice in
      the step through and step down tests, the conditioned and unconditioned avoidance
      responses of normal mice in the shuttle box and lever press performance tests,
      and the ambulatory activity of normal mice in normal condition. However, EE-SHT
      was shown to significantly decrease the spontaneous motor activity during the
      shuttle box test, and also to prolong the sleeping time induced by pentobarbital
      in mice at 20mg/kg. These results suggest that EE-SHT has an ameliorating effect
      on memory retrieval impairment and a weak tranquilizing action.

PMID- 16973320
TI  - Ligusticum chuanxiong prevents rat pheochromocytoma cells from serum deprivation
      induced apoptosis through a protein kinase A-dependent pathway.
AB  - Ligusticum chuanxiong (LC) is a traditional Chinese herbal medicine used to treat
      various cardiovascular diseases. In this study, the butanol extract of LC was
      found to protect neuronal-like pheochromocytoma cells from serum deprivation
      induced apoptosis. Both a serine/threonine kinase inhibitor and a specific
      protein kinase A (PKA) inhibitor blocked the protective effect of LC. A
      transcription inhibitor (actinomycin D) and a protein synthesis inhibitor
      (cyclohexamide) also attenuated the protective effect of LC, suggesting the
      requirement of gene expression for the protection of LC. On the other hand, LC
      increased both the formation of cyclic-AMP and the phosphorylation of the cyclic
      AMP response element-binding protein (CREB), a downstream target of PKA and a
      nuclear transcription factor known for neuroprotective mechanism. Furthermore, LC
      induced CREB phosphorylation and protective effect could be blocked by a PKA
      inhibitor and overexpression of the dominant negative CREB, respectively. Taken
      together, the protective mechanism of LC in antagonizing serum deprivation
      induced PC12 cell apoptosis might be mediated through a PKA/CREB-dependent
      pathway.

PMID- 16973322
TI  - Modelling the buried human body environment in upland climes using three
      contrasting field sites.
AB  - Despite an increasing literature on the decomposition of human remains, whether
      buried or exposed, it is important to recognise the role of specific
      microenvironments which can either trigger or delay the rate of decomposition.
      Recent casework in Northern England involving buried and partially buried human
      remains has demonstrated a need for a more detailed understanding of the effect
      of contrasting site conditions on cadaver decomposition and on the
      microenvironment created within the grave itself. Pigs (Sus scrofa) were used as
      body analogues in three inter-related taphonomy experiments to examine
      differential decomposition of buried human remains. They were buried at three
      contrasting field sites (pasture, moorland, and deciduous woodland) within a 15
      km radius of the University of Bradford, West Yorkshire, UK. Changes to the
      buried body and the effect of these changes on hair and associated death-scene
      textile materials were monitored as was the microenvironment of the grave. At
      recovery, 6, 12 and 24 months post-burial, the extent of soft tissue
      decomposition was recorded and samples of fat and soil were collected for gas
      chromatography mass spectrometry (GCMS) analysis. The results of these studies
      demonstrated that (1) soil conditions at these three burial sites has a marked
      effect on the condition of the buried body but even within a single site
      variation can occur; (2) the process of soft tissue decomposition modifies the
      localised burial microenvironment in terms of microbiological load, pH, moisture
      and changes in redox status. These observations have widespread application for
      the investigation of clandestine burial and time since deposition, and in
      understanding changes within the burial microenvironment that may impact on
      biomaterials such as hair and other associated death scene materials.

PMID- 16973321
TI  - Mechanisms of the anti-hypertensive effect of Hibiscus sabdariffa L. calyces.
AB  - Previous studies have demonstrated the anti-hypertensive effects of Hibiscus
      sabdariffa L. (HS) in both humans and experimental animals. To explore the
      mechanisms of the anti-hypertensive effect of the HS, we examined the effects of
      a crude methanolic extract of the calyces of HS (HSE) on vascular reactivity in
      isolated aortas from spontaneously hypertensive rats. HSE relaxed, concentration
      dependently, KCl (high K(+), 80 mM)- and phenylephrine (PE, 1 microM)-pre
      contracted aortic rings, with a greater potency against the alpha(1)-adrenergic
      receptor agonist. The relaxant effect of HSE was partly dependent on the presence
      of a functional endothelium as the action was significantly reduced in
      endothelium-denuded aortic rings. Pretreatment with atropine (1 microM), L-NAME
      (10 microM) or methylene blue (10 microM), but not indomethacin (10 microM),
      significantly blocked the relaxant effects of HSE. Endothelium-dependent and 
      independent relaxations induced by acetylcholine and sodium nitroprusside,
      respectively, were significantly enhanced in aortic rings pretreated with HSE
      when compared to those observed in control aortic rings. The present results
      demonstrated that HSE has a vasodilator effect in the isolated aortic rings of
      hypertensive rats. These effects are probably mediated through the endothelium
      derived nitric oxide-cGMP-relaxant pathway and inhibition of calcium (Ca(2+))
      influx into vascular smooth muscle cells. The present data further supports
      previous in vivo findings and the traditional use of HS as an anti-hypertensive
      agent.

PMID- 16973323
TI  - A quick and automated method for profiling heroin samples for tactical
      intelligence purposes.
AB  - A computerized procedure is presented for the profiling and comparison of illicit
      heroin seizures. The system involves the derivation and gas chromatographic
      separation of five major constituents followed by a fully automatic data analysis
      and transfer to a PHP/MySQL database. Comparisons via the square cosine function
      between a single chromatographic profile and the whole database (several hundred
      of samples) are performed in a few seconds. Advantages of this profiling method
      compared to the classical minor constituents one are discussed.

PMID- 16973324
TI  - The efficacy of sodium valproate and a MRA finding in confusional migraine.
AB  - Confusional migraine (CM) is recognized as a kind of pediatric migraine
      equivalent. We report that a 10-year-old girl had repeated attacks of confusional
      state and of migraine with aura. She suffered from total of six CM attacks and
      migraine attacks with aura almost once a month. Therefore, sodium valproate (VPA)
      was initiated to prevent these attacks. They have been controlled after
      increasing her dosage to 600mg/day. The intracranial magnetic resonance
      angiography (MRA) during the last CM attack indicated narrowing of left middle
      and posterior cerebral arteries. However, MRA during the attack free period at 41
      day follow-up showed normal vessels. Electroencephalograms showed severe slowing
      without seizure discharges during the CM attacks. This case indicates that VPA is
      an effective treatment for the prophylaxis of CM and migraine with aura. MRA is
      considered helpful for the diagnosis of this kind of migraine in children because
      of noninvasive neuroimaging.

PMID- 16973325
TI  - Imaging of the neonatal CNS.
AB  - Imaging of the central nervous system is one of the major tasks of Paediatric
      Radiology, particularly in newborns, who present with a variety of conditions
      that need more or less urgent imaging. Imaging is usually performed primarily by
      bedside US, in rare cases supplemented by a skull or spine radiograph. For more
      detailed information and preoperatively, MRI has become the neuroimaging tool.
      Thus, CT today is only used for acute trauma assessment, for assessment of
      potential cerebral calcifications or when MRI is not available. In cases with
      vascular anomalies or unsuccessful punctures, image guided interventions
      (embolisation) or image guidance for access (lumbar puncture, puncture of skull
      collections ...) may become necessary. This article tries to give a brief
      overview on the common disease entities, their typical imaging features in the
      major modalities applied and the implications of imaging potential for indication
      and choice of imaging method. In general, acute assessment may become everywhere
      and major features of important diseases should be recognised not to miss
      conditions which need urgent treatment or referral to a dedicated paediatric
      unit. Many other conditions will only be seen at centres with a dedicated
      neonatal care unit and dedicated paediatric radiologist who then also will be
      able to provide proper imaging with adapted protocols and methods for these
      partially severely sick babies. As these specific features and adapted
      capabilities as well as dedicated training and clinical experience are necessary
      for providing best results and proper handling in neonates, many neonatal
      conditions will not be imaged at a peripheral site, but primarily should be
      referred to a paediatric (radiology) centre.

PMID- 16973326
TI  - Contrast agents for functional and cellular MRI of the kidney.
AB  - Low-molecular-weight gadolinium (Gd) chelates are glomerular tracers but their
      role in evaluation of renal function with magnetic resonance (MR) imaging is
      still marginal. Because of their small size, they diffuse freely into the
      interstitium and the relationship between measured signal intensity and
      concentration is complex. New categories of contrast agents, such as large Gd
      chelates or iron oxide particules, with different pharmacokinetic and magnetic
      properties have been developed. These large molecules could be useful for both
      functional (quantification of perfusion, quantification of glomerular filtration
      rate, estimation of tubular function) and cellular imaging (intrarenal
      phagocytosis in inflammatory renal diseases). Continuous development of new
      contrast agents remains worthwhile to get the best adequacy between the
      physiological phenomenon of interest and the pharmacokinetic of the agent.

PMID- 16973327
TI  - Large needle percutaneous aspiration biopsy of the testicle in men with
      nonobstructive azoospermia: technical performance.
AB  - The aim of this study was to relate retrospectively in 215 percutaneous large
      needle aspiration biopsy (LNAB) of the testicles the number of seminiferous
      tubules (ST) per testicular biopsy, from differently sized testicles, to the size
      of the needle used in order to obtain information useful for selecting the needle
      size according to the testicular size. Clinical, ultrasonographic and pathologic
      data of 134 patients with nonobstructive azoospermia examined with LNAB were
      retrospectively analyzed. One hundred and sixty-three testicles with volume>or=10
      ml, 39<10 ml and>or=6 ml, 13<6 ml underwent 215 LNABs. In the larger testicle
      group the prevalence of adequate biopsies (ST>/=20) varied from 83% to 50% with a
      statistically significant difference among the needle groups (P=0.028) and being
      83% in the biopsies with the 18 gauge (g.) needle. The mean number of ST obtained
      with the 18 g. needle was significantly higher than that obtained with the other
      needles (P=0.000). In the medium volume testicle group the adequate biopsy
      incidence varied from 20% to 83.3% with statistical significance among the
      various needle groups (P=0.042) being 83.3% in the biopsies with the 22 g.
      needle. In the smaller testicle group the mean number of ST obtained with the 22
      g. needle was significantly higher than with the 20 g. needle (71 versus 25,
      P=0.011). In the patients with nonobstructive azoospermia, the 18 g. needle
      seemed to offer the best performance in the larger testicles, while in the medium
      and lower sized testicles the smaller 22 g. needle gave results comparable to or
      slightly better than the other larger needles.

PMID- 16973328
TI  - Endometrial damage and apoptosis in rats induced by dichlorvos and ameliorating
      effect of antioxidant vitamins E and C.
AB  - We aimed to investigate the effect of subchronic administration of dichlorvos
      (DDVP) on endometrium and to evaluate ameliorating effects of a combination of
      Vitamins E and C against DDVP toxicity in the rat. Three groups of rats were used
      in the experiment. The first group was treated with 4 mg/kg DDVP; the second
      group was treated with 4 mg/kg body weight DDVP plus Vitamins E and C (DDVP+Vit);
      the third group was given only corn oil (control). DDVP and DDVP+Vit groups were
      given DDVP by gavage 5 days a week for 4 weeks at a dose level of 4 mg/kg day by
      using corn oil as the vechicle. Vitamins E and C were injected at doses of 50
      mg/kg i.m. and 20 mg/kg body weight i.p. Histopathological and
      immunohistochemical examinations for caspase-3 and caspase-9 were accomplished in
      the endometrium. The level of malondialdehyde (MDA) increased significantly in
      the DDVP group compared with the control group (p<0.05). MDA significantly
      decreased in the DDVP+Vit group compared with the DDVP group (p<0.05).
      Administration of Vitamins E and C along with DDVP significantly reduced the
      histopathological changes and the extent of apoptosis. In conclusion, subchronic
      DDVP administration caused endometrial damage and that treatment with a
      combination of Vitamins E and C reduced endometrial damage caused by DDVP.

PMID- 16973329
TI  - Assessing challenging behaviors in children with autism spectrum disorders: a
      review.
AB  - A common covarying group of behaviors with ASD are self-injury, aggression,
      noncompliance, and stereotypies. These problems and related challenging behaviors
      are problematic in that they are physically dangerous and can impede learning and
      access to normal activities. Additionally, they require a considerable amount of
      resources, and compound the difficulty in treating core ASD symptoms. Despite the
      high profile challenging behaviors present in this population, there has not been
      a great deal of research regarding assessment, identification, and monitoring of
      such difficulties. This review covers available empirical based methods for
      assessing these behaviors. A discussion is provided of potential avenues for
      future research and clinical practice which is urgently needed for ASD children
      at this time.

PMID- 16973330
TI  - Oxidative stress employs phosphatidyl inositol 3-kinase and ERK signalling
      pathways to activate cAMP phosphodiesterase-4D3 (PDE4D3) through multi-site
      phosphorylation at Ser239 and Ser579.
AB  - RAW macrophages, which express the PDE4D3 and PDE4D5 cAMP phosphodiesterase
      isoforms, exhibited increased PDE4 activity when challenged with H2O2 in a
      fashion that was negated by treatment with the cell permeant antioxidant, N
      acetyl cysteine and by diphenyleneiodonium chloride, an inhibitor of NADPH
      oxidase. In Cos1 cells transfected to express PDE4D3, challenge with H2O2 caused
      a rapid increase in both the activity and phosphorylation of PDE4D3. Lysates from
      H2O2-treated COS cells caused the phosphorylation of purified, recombinant PDE4D3
      at two sites. One was the established ERK phosphorylation site at Ser579, located
      at the extreme C-terminus of the catalytic unit, and the other was a novel site
      at Ser239, located at the extreme N-terminus of the catalytic unit. Double
      Ser239Ala:Ser579Ala mutation of PDE4D3 prevented its H2O2-dependent
      phosphorylation both in vitro and in intact COS cells. Phosphorylation of PDE4D3
      at Ser579 was ablated by treating COS cells with the MEK inhibitor, PD98059,
      which also negated activation. The activity of the Ser239Ala:Ser579Ala double
      mutant, and the Ser579Ala single PDE4D3 mutant was unaffected by H2O2 challenge
      of COS cells, whilst the Ser239Ala mutant was inhibited. Wortmannin inhibited the
      H2O2-dependent phosphorylation of PDE4D3 in COS cells by around 50%, whilst it
      fully ablated phosphorylation at Ser239 as well as ablating activation of PDE4D3.
      Neither immunodepletion of p70S6 kinase nor siRNA-mediated knockdown of mTor
      inhibited the H2O2-dependent phosphorylation of PDE4D3 at Ser239. Activation of
      PDE4D3 by challenge with H2O2 was not additive with activation through protein
      kinase A (PKA)-mediated phosphorylation of PDE4D3. Challenge with H2O2 did not
      alter PKA-mediated phosphorylation of PDE4D3 at Ser54. H2O2 dependent
      phosphorylation of PDE4D3, at Ser239 and Ser579, did not alter the sensitivity of
      PDE4D3 to inhibition by the selective PDE4 inhibitor, rolipram. An unknown
      protein kinase acting downstream of phosphatidyl inositol 3-kinase phosphorylates
      PDE4D3 at Ser239. This switches the effect of phosphorylation by ERK at Ser579
      from inhibition to activation. We propose that phosphorylation at Ser239
      attenuates interaction between either UCR2 or the UCR1/UCR2 module and the PDE4
      catalytic unit so as to re-programme the functional outcome effect of
      phosphorylation by ERK. We identify a novel process through which reactive oxygen
      species activate long PDE4 isoforms so as to reduce cAMP levels and thereby
      promote inflammatory responses.

PMID- 16973331
TI  - Comparison of metabolic monitors in critically ill, ventilated patients.
AB  - OBJECTIVE: We compared the Deltatrac II, the M-COVX, and the Evita 4 metabolic
      monitoring devices under clinical conditions. METHODS: A prospective simultaneous
      clinical comparison was performed in a general intensive care department of a
      tertiary university hospital in 43 ventilated, critically ill patients. The
      monitors were compared simultaneously. After 30 min of steady state, oxygen
      consumption per unit time, carbon dioxide consumption per unit time, resting
      energy expenditure, and respiratory quotient were recorded for the Deltatrac II;
      the same parameters in addition to end-tidal carbon dioxide and fraction of
      inspired oxygen were recorded for the M-COVX; and carbon dioxide consumption per
      unit time, end-tidal carbon dioxide, and fraction of inspired oxygen were
      recorded for the Evita 4. Pulmonary gas-exchange measurements from the Deltatrac
      II and resting energy expenditure and respiratory quotient from the M-COVX were
      obtained after 30 min. The other parameters were calculated from the last five
      measurements obtained at the end of the study period. RESULTS: A good correlation
      was found between oxygen consumption per unit time and resting energy expenditure
      as obtained from the Deltatrac II and the M-COVX (r = 0.76 and 0.75,
      respectively; P < 0.001), but the correlation was lower between carbon dioxide
      consumption per unit time as obtained from the Deltatrac II and the M-COVX or
      Evita 4 (r = 0.67 and 0.48, respectively). Agreement between the different
      methods did not reach clinical acceptability, exceeding a 20% difference using
      the Bland-Altman statistical methods. CONCLUSION: Poor agreement was found
      between the Deltatrac II and M-COVX or Evita 4 metabolic monitors, despite a good
      correlation between measurements, leading to the conclusion that the M-COVX and
      Evita 4 provide less accurate measurements of metabolic gas exchange in stable
      ventilated patients. These devices can be used for daily nutritional assessment
      and continuous monitoring, but the Deltatrac II remains the method of choice for
      metabolic measurement.

PMID- 16973332
TI  - Histomorphometric evaluation of guided bone regeneration around implants with SLA
      surface: an experimental study in beagle dogs.
AB  - The aim of this study was to evaluate the efficacy of collagen membranes, either
      alone or combined with a human demineralized freeze-dried bone allograft (DFDBA)
      or natural bovine bone graft, in bone defects around dental implants with an SLA
      (sand-blasted, large grit, acid-etched) surface. The experiments were carried out
      in three beagle dogs using a split-mouth design. On one side of the jaw, three
      implants were placed and intra-bony defects were created and covered with a
      collagen membrane, randomly combined in two of the defects with human DFDBA or
      inorganic bovine bone graft. A control implant, without membrane covering or
      defect filling, was also placed. On the other side of the jaw, three implants
      were placed and the bone defects were treated in a similar fashion, but without
      membrane covering. The studied variables were the percentage of bone-to-implant
      contact within the limits of the initial bony defect and percentage of the
      original bony defect occupied by bone tissue. Although no statistically
      significant differences were found in this study between the membrane and
      nonmembrane groups, bone defects augmented with anorganic bovine bone and
      membranes showed the most promising results from a histological and
      histomorphometric perspective.

PMID- 16973333
TI  - Topical capsaicin reduces ultraviolet radiation-induced suppression of Mantoux
      reactions in humans.

PMID- 16973334
TI  - Peptidylarginine deiminases and deimination in biology and pathology: relevance
      to skin homeostasis.
AB  - Deimination corresponds to the transformation of arginine residues within a
      peptide sequence into citrulline residues. Catalyzed by peptidylarginine
      deiminases, it decreases the net positive charge of proteins, alters intra and
      intermolecular ionic interactions and probably the folding of target proteins.
      Deimination has recently been implicated in several physiological and
      pathological processes. Here, we describe the enzymes involved in this post
      translational modification, focusing on their expression, location and roles in
      skin, as well as their known protein substrates in the epidermis and hair
      follicles. We discuss also the potential involvement of deimination in human
      diseases including cutaneous disorders.

PMID- 16973335
TI  - Effect of artesunate and artemether against Clonorchis sinensis and Opisthorchis
      viverrini in rodent models.
AB  - Food-borne trematodiasis is an emerging public health problem and there is a need
      to develop novel treatment options. We examined the in vivo efficacy of single
      oral doses of artesunate and artemether administered to rodents experimentally
      infected with either Clonorchis sinensis or Opisthorchis viverrini. Rats infected
      with adult C. sinensis were administered artesunate or artemether at doses of 75,
      150 or 300 mg/kg. Hamsters infected with adult O. viverrini were administered
      artesunate or artemether at doses of 200, 400 or 600 mg/kg. Treatment efficacy
      was assessed according to reductions in worm burden compared with infected but
      untreated control animals. Worm burden reductions of 98.6-100% were found in C.
      sinensis-infected rats after a single dose of artesunate and artemether at 150
      mg/kg. Administration of artesunate and artemether at a dose of 400mg/kg to O.
      viverrini-infected hamsters resulted in worm burden reductions of 77.6% and
      65.5%, respectively. However, both drugs showed toxic effects when administered
      to O. viverrini-infected hamsters at a dose > or =400mg/kg. Our study
      demonstrates that artesunate and artemether possess excellent clonorchicidal
      activities in vivo. These findings provide a foundation for subsequent clinical
      trials. More laboratory investigations are warranted to investigate further the
      opisthorchicidal properties of the artemisinins.

PMID- 16973336
TI  - Macrolide, lincosamide and tetracycline susceptibility and emm characterisation
      of invasive Streptococcus pyogenes isolates in Israel.
AB  - Group A beta-haemolytic streptococcus (GAS) causes a variety of infections,
      including life-threatening illnesses. Although the species is uniformly
      penicillin susceptible, resistance to other antibiotics is becoming more common.
      We studied the prevalence of resistance and associated factors in a nationwide,
      prospective, population-based study of invasive infections in Israel. Isolates
      were collected in collaboration with 24 hospitals in Israel during 1996-1999.
      Minimal inhibitory concentrations (MICs) of erythromycin (ERY), clindamycin (CLI)
      and tetracycline (TET) were determined as well as ERY and TET resistance
      phenotypes and genotypes. Five hundred isolates were examined: 136 (27.2%) were
      not susceptible to TET, 10 (2.0%) to ERY and 5 (1%) to CLI. ERY resistance was
      associated with emm types 12 and 83 (P<0.001 for both). MICs of TET had a bimodal
      distribution distinguishing sensitive and resistant populations. Non
      susceptibility to TET was mainly due to the presence of tet(M) and was associated
      with T types 3, 3/13/B3624 and 9 and emm types 9, 33, 64, 73, 74, 76, 77 and 83.
      TET susceptibility was associated with T types 1, 2 and 11, emm types 1-4, 11,
      12, 22, 26 and 75 and the presence of speA and speC. In Israel, resistance of
      invasive GAS isolates to ERY remains low and is associated with specific T and
      emm types, as is TET resistance. TET resistance is less frequent than previously
      reported in Israel and is associated with a lower prevalence of speA and speC.

PMID- 16973337
TI  - Trends in penicillin and macrolide resistance among pneumococci in the UK and the
      Republic of Ireland in relation to antibiotic sales to pharmacies and dispensing
      doctors.
AB  - It is widely believed that reducing antimicrobial usage should reduce resistance,
      although observational evidence is mixed. Pneumococci make ideal subjects to test
      this belief as they are widely surveyed and lack an animal reservoir.
      Accordingly, susceptibility data for pneumococci in the UK and Ireland were
      retrieved from the Health Protection Agency's LabBase/CoSurv system and from the
      European Antimicrobial Resistance Surveillance System (EARSS) and British Society
      for Antimicrobial Chemotherapy (BSAC) databases. The BSAC surveillance examines
      respiratory pneumococci; the other systems focus upon invasive organisms only,
      with the LabBase/CoSurv system being the most comprehensive, capturing data on
      most bacteraemias in England and Wales. National pharmacy sales data were
      obtained from the IMS Health MIDAS database and were modelled to the resistance
      data by logistic and linear regression analysis. All systems except for the BSAC
      respiratory surveillance data indicated that penicillin resistance has fallen
      significantly since 1999 in the UK, whereas macrolide resistance has been
      essentially stable, or has risen slightly. The data for Ireland were based on
      smaller sample sizes but suggested a fall in penicillin non-susceptibility from
      1999 to 2004, with conflicting evidence for macrolide resistance. The recent
      decreasing trend in penicillin resistance is in contrast to a rising trend in
      England and Wales until (at least) 1997 and strongly rising macrolide resistance
      from 1989 to 1993. UK pharmacy sales of macrolides and oral beta-lactams fell by
      ca. 30% in the late 1990s following increased concern about resistance, before
      stabilising or rising weakly; sales in Ireland were stable or rose slightly in
      the study period. We conclude that falling penicillin resistance in pneumococci
      followed reduced sales of oral beta-lactams to pharmacies in the UK, but a
      similar fall in macrolide sales was not associated with any fall in resistance.
      Stabilisation or decline in penicillin resistance has occurred in Ireland despite
      stable or increasing oral beta-lactam sales.

PMID- 16973338
TI  - Amyotrophic lateral sclerosis as a complex genetic disease.
AB  - In complex diseases like ALS, there are multiple genetic and environmental
      factors all contributing to disease liability. The genetic factors causing
      susceptibility to developing ALS can be considered a spectrum from single genes
      with large effect sizes causing classical Mendelian ALS, to genes of smaller
      effect, producing apparently sporadic disease. We examine the statistical genetic
      principles that underpin this model and review what is known about ALS as a
      disease with complex genetics.

PMID- 16973339
TI  - Carboxyhemoglobin and thiocyanate as biomarkers of exposure to carbon monoxide
      and hydrogen cyanide in tobacco smoke.
AB  - The determination of biomarkers in human body fluids is a useful tool, which
      allows the quantitative assessment of the exposure to chemicals or complex
      mixtures of chemicals and of early biological effects as a result of the
      exposure. Biomarkers require validation before their successful application in
      human studies. This review describes some general purposes of human biomonitoring
      and biomarkers including the requirements for validation. Risk assessment and
      harm reduction of smoking and tobacco products, respectively, is a very suitable
      field for the application of biomarkers. A brief historical review shows that the
      application of biomarkers of exposure and effect in human smoking goes back more
      than 150 years. Two 'classical' biomarkers of exposure to tobacco, namely
      carboxyhemoglobin (COHb and its equivalent carbon monoxide in exhalate, COex) and
      thiocyanate (SCN) in body fluids are discussed in terms of sources of exposure,
      metabolism, disposition kinetics and influencing host factors. Data on COHb/COex
      and SCN in nonsmokers and smokers as well as the power to discriminate between
      smokers and nonsmokers are presented. Both biomarkers are significantly
      correlated with the daily cigarette consumption. Smoking machine-derived yields
      of the precursors carbon monoxide and hydrogen cyanide were not correlated with
      COHb/COex and SCN, respectively. It is concluded that, while COHb/COex is a
      useful biomarker for assessing the smoke inhalation, preferably in controlled
      studies, the application of SCN in body fluids as a biomarker for smoking is
      limited, mainly due to the abundance of other sources for SCN.

PMID- 16973340
TI  - Binding of STW 5 (Iberogast) and its components to intestinal 5-HT, muscarinic
      M3, and opioid receptors.
AB  - Clinical studies with the fixed herbal combination product STW 5 (Iberogast) have
      indicated an efficacy comparable to metoclopramide (5-HT(3) antagonist) and
      cisapride (5-HT(4) agonist) in functional gastro-intestinal diseases like
      functional dyspepsia (FD) and irritable bowel syndrome (IBS). Since serotonin (5
      HT(3) and 5-HT(4)) and muscarinic M(3) receptors are known to play a central role
      in the etiology of FD and IBS, the extracts contained in STW 5 and several of
      their phytochemical components were studied in vitro for binding affinities to
      these receptors of the intestine. STW 5 inhibited the binding of (3)H-GR113808
      and (3)H-4-DAMP to 5-HT(4) and M(3) receptors, respectively, about 10 times more
      potently than the binding of (3)H-GR65630 to 5-HT(3) receptors. IC(50) values for
      STW 5 did correspond to extract dilutions of 1:1000 (M(3) binding) and 1:2000 (5
      HT(4) binding). In addition, STW 5 also potently inhibited the binding to opioid
      receptors with an IC(50) value of 1:2000. Of the nine herbal extracts contained
      in STW 5, the fresh plant extract of bitter candy tuft (Iberis amara) selectively
      inhibited binding to M(3) receptors, while ethanolic extracts of celandine herb
      and chamomile flower were selective to 5-HT(4), and liquorice root to 5-HT(3)
      receptors. Binding affinities to human recombinant 5-HT(3), 5-HT(4) and M(3)
      receptors were qualitatively similar to those of the corresponding intestinal
      receptors. The benzylisoquinoline alkaloid berberine had significant inhibitory
      action on 5-HT(4) and M(3) binding, showing IC(50) values of 40 ng/ml (100 nM)
      and 200 ng/ml (500 nM), respectively, but is present in the extract of celandine
      herb only in traces, so that also for the celandine extract a cooperative effect
      of several phytochemical constituents can be assumed. These in vitro data
      indicate that 5-HT(4) (to a lesser degree 5-HT(3)), muscarinic M(3), and opioid
      receptors represent target sites for the treatment of FD and IBS with STW 5
      (Iberogast).

PMID- 16973341
TI  - Collagen type V enhances matrix contraction by human periodontal ligament
      fibroblasts seeded in three-dimensional collagen gels.
AB  - Extracellular matrix components play an important role in modulating cellular
      activity. To study such capacities of the matrix, fibroblasts are frequently
      cultured in a three-dimensional gel and contraction is assessed as a measure of
      cellular activity. Since a connective tissue contains several types of collagen,
      we investigated the effect of gels composed of collagen I alone or in combination
      with 10% collagen III and/or 5% collagen V on contraction by human periodontal
      ligament fibroblasts. Gels containing collagen V contracted much faster than
      those without this type of collagen. Blocking of the integrin beta1-subunit with
      an activity-blocking antibody delayed (gels with collagen V) or almost completely
      blocked (gels without collagen V) contraction. Use of an antibody directed
      against integrin alpha2beta1 resulted in delay of gel contraction for gels both
      with and without collagen V. Anti-integrin alpha v beta3 or RGD peptides
      partially blocked contraction of gels containing collagen V, but had no effect on
      gels consisting of collagen I alone. The beta1-containing integrins are involved
      in the basal contraction by fibroblasts that bind to collagens I and III. The
      enhanced contraction, stimulated by collagen V, appears to be mediated by
      integrin alpha v beta3. We conclude that collagen V may play an important
      modulating role in connective tissue contraction. Such a modulation may occur
      during the initial stages of wound healing and/or tissue regeneration.

PMID- 16973342
TI  - Omega-3 fatty acids and rodent behavior.
AB  - This paper reviews the role of the n-3 fatty acids in the regulation of cognitive
      functions, locomotor and exploratory activity and emotional status in rodents.
      There are disparate data on the performance of n-3 fatty acid deficient animals
      in the open field test and elevated plus maze. Results obtained in our laboratory
      indicated slower habituation to the open field in deficient mice, which affects
      total locomotor and exploratory parameters. We also observed no change in plus
      maze performance of deficient mice under low-stress but elevated anxiety under
      high-stress conditions. There is some evidence of elevated aggression and
      increased immobility time in the forced swimming test caused by n-3 fatty acid
      deficiency in rodents. Effects of n-3 fatty acid deficiency and supplementation
      on learning in several tests such as the Morris water maze, two odor olfactory
      discriminations, radial arm maze performance and avoidance tasks are reviewed in
      detail. There is some evidence of an enhanced vulnerability to stress of n-3
      fatty acid deficient animals and this factor can influence performance in a
      variety of tests. Thus, behavioral tasks that involve a higher level of stress
      may better differentiate behavioral effects related to brain docosahexaenoic acid
      (DHA) status. It is suggested that a fruitful area for future investigations of
      functional alterations related to brain DHA status will be the delineation of the
      factors underlying changes in performance in behavioral tasks. The possible role
      of non-cognitive factors like emotionality and attention in the impaired
      performance of n-3 fatty acid deficient animals also requires further
      investigation.

PMID- 16973343
TI  - Genetics of autoimmune neuroinflammation.
AB  - Detection of gene variants affecting the risk for multiple sclerosis provides
      insights into mechanisms central for autoaggressive neuroinflammation. Major
      histocompatibility complex (MHC) class II genes, and probably also MHC class I
      genes, regulate both human multiple sclerosis and rodent experimental autoimmune
      encephalomyelitis. However, the functional understanding of the MHC regulation
      requires further experimentation. Genome scans in human multiple sclerosis have
      failed to demonstrate significant non-MHC loci with genome-wide significance, but
      approximately 50 such loci have been described in different rodent experimental
      autoimmune encephalomyelitis models. Positional cloning of individual rodent
      genes is difficult, but genes or small genome regions now emerge. Association
      studies in large human cohorts are needed to confirm the human relevance of
      rodent genes and such cohorts will also be used for single nucleotide
      polymorphism-based whole-genome screening. It is realistic to assume that several
      non-MHC genes regulating autoimmune neuroinflammation, including target tissue
      responses, will be pinpointed in the next ten years. At the moment there are a
      few hot candidates, including MHC2TA, PRKCA and IL7R.

PMID- 16973344
TI  - The microcontact imprinting of proteins: the effect of cross-linking monomers for
      lysozyme, ribonuclease A and myoglobin.
AB  - The performance of molecularly imprinted polymers (MIPs) is of interest to
      researchers in the field of analytical chemistry, and in the pharmaceutical and
      food industries. Because the choice of the functional monomer(s) plays a key role
      in the selectivity of a MIP, the synthesis of an effective, tight-binding MIP can
      be difficult and time-consuming, involving the evaluation of the binding
      performance of MIPs of many different compositions. In this study, we report an
      express method combining molecular imprinting and microcontact printing
      techniques to prepare a polymer thin film as an artificial antibody. In addition
      to the microcontact printing technique, isothermal titration of monomers to
      proteins stamps was investigated to screen the functional monomer for MIPs.
      Finally, the importance of the choice of cross-linking monomers in MIPs was
      studied, and these studies suggest that monomers containing an optimal length PEG
      spacer give higher imprinting effectiveness. Several model antigens (lysozyme,
      ribonuclease A and myoglobin) were adsorbed on a cover glasses that were
      pretreated with hexamethyldisilazane (HMDS). These protein stamps were then
      contacted with different monomer solutions (cross-linking monomers) on a glass
      slide substrate. Photopolymerization yielded the molecularly imprinted polymer.
      This technique, analogous to microcontact printing, allows for the rapid,
      parallel synthesis of MIPs of different compositions, and requires very small
      volumes of monomers (ca. 4 microL). The technique also avoids potential
      solubility problems with the molecular targets. Of several cross-linking monomers
      screened, tetraethyleneglycol dimethacrylate (TEGDMA) gave the most selective
      lysozyme binding, while polyethyleneglycol 400 dimethacrylate (PEG400DMA) were
      most selective for ribonuclease A and myoglobin.

PMID- 16973345
TI  - The use of single walled carbon nanotubes dispersed in a chitosan matrix for
      preparation of a galactose biosensor.
AB  - Chitosan was chosen as a natural polymer for dispersion of single walled carbon
      nanotubes (SWNT) based on its ability to efficiently solubilize SWNTs to form a
      stable dispersion. Moreover, chitosan films deposited on a surface of a glassy
      carbon (GC) electrode are mechanically stable. Further stabilisation of the
      chitosan film containing SWNT (CHIT-SWNT) was done by chemical crosslinking with
      glutaraldehyde and free aldehyde groups produced a substrate used for covalent
      immobilisation of galactose oxidase (GalOD). Different galactose biosensor
      configurations were tested with optimisation of composition of inner and outer
      membrane; and enzyme immobilisation procedure, as well. Detection of oxygen
      uptake by GalOD on CHIT-SWNT layer at -400 mV is robust and, when flow injection
      analysis (FIA) was applied for assays, a low detection limit (25 microM) and very
      high assay throughput rate (150 h-1) was achieved. This new galactose biosensor
      offers highly reliable detection of galactose with R.S.D. well below 2% and it
      has been successfully applied to assaying galactose in a blood sample with
      recovery index between 101.2 and 102.7%.

PMID- 16973347
TI  - Pyrazolo[3,4-d]pyrimidines c-Src inhibitors reduce epidermal growth factor
      induced migration in prostate cancer cells.
AB  - During its biological progression, prostate cancer frequently develops dependence
      on growth factor receptors and their downstream signalling messengers, including
      c-Src. Evidence for this supports the choice of c-Src as a therapeutic target in
      the prevention of tumour spreading. Two new pyrazolo[3,4-d]pyrimidines c-Src
      inhibitors, SI35 and SI40, were used to investigate the role of c-Src in the
      control of the aggressive phenotype of prostate carcinoma cell line, PC3. SI
      molecules reduced the proliferation of PC3 cells in a time- and dose-dependent
      manner, with an IC50 of approximately 50 microM. PC3 cells responded to the
      presence of epidermal growth factor (EGF) by increasing their migratory ability,
      and this effect was strongly reduced by the addition of SI at concentrations less
      than IC50. Further observations demonstrated that SI molecules modulated cell
      morphology and their adhesive capacity on different physiological substrates. The
      action of SI molecules appeared to involve, in parallel with c-Src inhibition,
      the down-modulation of the active forms of paxillin and extracellular signal
      regulated kinase (ERK). Our data suggest a promising role for pyrazolo[3,4
      d]pyrimidines c-Src inhibitors in the control of a highly invasive tumour
      phenotype.

PMID- 16973348
TI  - Up-regulation of gelatinases in the colorectal adenoma-carcinoma sequence.
AB  - Gelatinase activity has been associated with colorectal cancer (CRC) invasion and
      metastasis. However, it remains unresolved whether these proteases participate in
      early colorectal carcinogenesis. The activity of metalloproteinases (MMP) 2 and 9
      were measured by zymography in 122 colorectal adenomas, 22 CRC samples, 12
      hyperplasic polyps and in 114 matched normal mucosal samples from 114 patients
      undergoing colonoscopy. There was a progressive and significant increase of pro
      MMP-9 activity from adenoma to CRC tissue, whereas the activity of the latent and
      active forms of MMP-2 was exclusively up-regulated in CRC samples. Among
      neoplastic polyps, pro-MMP-9 activity was significantly higher in advanced versus
      non-advanced adenomas and in those harbouring high grade dysplasia. In addition,
      a positive correlation was observed between MMP-9 activity and the size of the
      adenomas. The present study demonstrates that MMP-9 is markedly up-regulated in
      the adenomatous tissue and suggests that this gelatinase might be a marker for
      early colorectal carcinogenesis.

PMID- 16973349
TI  - Anti-angiogenic, vascular-disrupting and anti-metastatic activities of
      vinflunine, the latest vinca alkaloid in clinical development.
AB  - The aim of this study was to investigate the anti-angiogenic, vascular-disrupting
      and anti-metastatic properties of vinflunine, the latest vinca alkaloid in phase
      III clinical development. The effects of vinflunine on in vitro endothelial cell
      functions relevant to the performance of an already formed vasculature and to the
      angiogenic process were evaluated. The in vivo anti-angiogenic properties of
      vinflunine were also investigated, as were its activity against a model of
      experimental metastasis. In vitro vinflunine induced a rapid change in the
      morphology of endothelial cells and disrupted the network of capillary-like
      structures, indicating potential vascular-disrupting activity. Furthermore,
      vinflunine showed anti-angiogenic properties, since it inhibited endothelial cell
      migration and the capacity of these cells to organise into a network of capillary
      like structures. All these effects were observed under conditions that only
      marginally affect endothelial cell proliferation. In vivo, vinflunine inhibited
      bFGF-induced angiogenesis in Matrigel implants at doses 40-20-fold lower than its
      maximal therapeutic dose (MTD). Treatment of mice with vinflunine reduced the
      number of liver metastases induced by intrasplenic injection of LS174T cells,
      with significant effects also observed at low doses; i.e. 16-fold lower than the
      MTD. This study demonstrates that vinflunine expresses both vascular-disrupting
      and anti-angiogenic activities and induced marked effects against experimental
      metastases, all properties that support its ongoing clinical development.

PMID- 16973350
TI  - Expression of p16(INK4a) in relation to histopathology and viral load of 'high
      risk' HPV types in cervical neoplastic lesions.
AB  - A total of 91 cervical archival biopsy series were analysed for the presence and
      viral load of 'high-risk' types of human papillomavirus (HR-HPV), and p16(INK4a)
      expression. The women had various degrees of CIN (cervical intraepithelial
      neoplasia). HPV 16 was the most prevalent type found, at 47% frequency. The
      frequency of HPV 16 increased with increasing immunoreactivity to p16(INK4a),
      from 39% to 44% at cases scored low to medium, to 65% at high reactivity. Thirty
      (33%) of the samples had negative p16(INK4a) analysis results, but were positive
      for HR-HPV. There was no significant correlation between viral load and the level
      of p16(INK4a) expression, while the grade of CIN correlated to such expressions.
      Thus, p16(INK4a) expression analysis yielded information which is consistent with
      results from the histopathology and might complement the HPV analysis in a
      clinical prognostic procedure in order to find women at risk for cervical cancer.

PMID- 16973351
TI  - Estrogenic activity of triterpene glycosides in yeast two-hybrid assay.
AB  - Estrogenic potency of six triterpene glycosides, Holothurin A, Holotoxin A1,
      Frondoside A, Cucumarioside A2-2 and Cauloside C, that are natural products and
      semi-synthesized Ginsenoside-Rh2, were examined with yeast two-hybrid system,
      including expressed genes of human estrogen receptor, hERalpha, the co-activator
      TIF2 and lacZ as a reporter gene. Only Ginsenoside-Rh2 exhibited significant
      moderate estrogenic activity in the concentration range of 10(-7) to 10(-6)M. Its
      effect was approximately 30% of the activity of 17beta-estradiol applied at half
      effective concentration. This indicates Ginsenosides-Rh2 is a weak phytoestrogen.
      The sea cucumber triterpene glycosides, Holothurin A, Holotoxin A1, Cucumarioside
      A2-2 and Frondoside A, and plant glycoside Cauloside C had no appreciable
      estrogenic activity. Data obtained by yeast two-hybrid assay reflect structure
      activity relationship between tested compounds and 17beta-estradiol. Only
      Ginsenoside-Rh2 has some similarity in chemical structure with 17beta-estradiol
      that might explain affinity of this glycoside to the hERalpha receptor.

PMID- 16973352
TI  - Physicochemical properties of carbons prepared from pecan shell by phosphoric
      acid activation.
AB  - Activated carbons were prepared from pecan shell by phosphoric acid activation.
      The pore structure and acidic surface groups of these carbons were characterized
      by nitrogen adsorption, Boehm titration and transmittance Fourier infrared
      spectroscopy (FTIR) techniques. The characterization results demonstrated that
      the development of pore structure was apparent at temperatures 250 degrees C, and
      reached 1130m(2)/g and 0.34cm(3)/g, respectively, at 500 degrees C. Impregnation
      ratio and soaking time at activation temperature also affected the pore
      development and pore size distribution of final carbon products. At an
      impregnation ratio of 1.5, activated carbon with BET surface area and micropore
      volume as high as 861m(2)/g and 0.289cm(3)/g was obtained at 400 degrees C.
      Microporous activated carbons were obtained in this study. Low impregnation ratio
      (less than 1.5) and activation temperature (less than 300 degrees C) are
      favorable to the formation of acidic surface functional groups, which consist of
      temperature-sensitive (unstable at high temperature) and temperature-insensitive
      (stable at high temperature) two parts. The disappearance of temperature
      sensitive groups was significant at temperature 300 degrees C; while the
      temperature-insensitive groups are stable even at 500 degrees C. FTIR results
      showed that the temperature-insensitive part was mostly phosphorus-containing
      groups as well as some carbonyl-containing groups, while carbonyl-containing
      groups were the main contributor of temperature-sensitive part.

PMID- 16973353
TI  - Anticoagulant activity of marine green and brown algae collected from Jeju Island
      in Korea.
AB  - Twenty-two algal species were evaluated for their potential anticoagulant
      activities. Hot water extracts from selected species, Codium fragile and
      Sargassum horneri showed high activated partial thromboplastin time (APTT).
      Ultraflo extract of C. fragile and S. horneri exhibited the most potent
      anticoagulant activity. Furthermore, in both algal species, active compounds were
      mainly concentrated in >30kDa faction. The crude polysaccharide fraction (>30kDa;
      CpoF) of C. fragile composed of approximately 80% carbohydrate and approximately
      19% of protein; the crude polysaccharide fraction (>30kDa; CpoF) of S. horneri
      was composed of 97% of carbohydrate and approximately 2% of protein. Therefore,
      most probably the active compound, or compounds of the algal species were related
      to high molecular weight polysaccharide, or a complex form with carbohydrate and
      protein (proteoglycan).

PMID- 16973354
TI  - Yield, size and bacterial blotch resistance of Pleurotus eryngii grown on
      cottonseed hulls/oak sawdust supplemented with manganese, copper and whole ground
      soybean.
AB  - Experiments were performed to determine effects of supplementation of cottonseed
      hull/sawdust substrate with Mn, Cu, and ground soybean on yield, mushroom size,
      and bacterial blotch resistance of two commercial strains of Pleurotus eryngii. A
      basal formulation (d.w.) of cottonseed hulls (62%), aged red oak sawdust (27%),
      whole ground soybean (6%), corn distiller's waste (4%) and calcium sulfate (1%)
      was supplemented to 50, 150 or 250 microg/g Mn or Cu and to 4%, 8% and 12% whole
      ground soybean. The cottonseed hulls content in the basal substrate was adjusted
      to compensate for the addition of ground soybean. Formulated substrates were
      mixed, placed in 1050ml bottles, and sterilized at 121 degrees C for 90min.
      Mushroom yields were significantly higher from substrates containing Mn at 50
      microg/g and soybean at 8% and 12% supplementation compared to the basal
      substrate. As the level of soybean addition to substrate increased, yield also
      increased. The addition of Mn at levels of 150 and 250 microg/g significantly
      enhanced yield as well, although less than did the 50 microg/g treatment. To
      assess the influence of mushroom strain and substrate composition on blotch
      disease severity, pilei of P. eryngii were inoculated with Pseudomonas tolaasii.
      Strain WC888 was more resistant to disease than WC846. Disease severity was
      greater when substrates were amended with Cu to 150 or 250 microg/g. There was a
      significant difference in inherent levels of Cu in the basidiomata of different
      strains, but P. eryngii did not accumulate Cu and disease severity was not
      correlated with Cu content of the basidiomata.

PMID- 16973355
TI  - Anaerobic treatment of cassava starch extraction wastewater using a horizontal
      flow filter with bamboo as support.
AB  - Small-scale sour starch agroindustry in Colombia suffer from absence of water
      treatment. Although starch processing plants produce diluted wastewater, it is a
      source of pollution and cause environmental problems to the nearby rural
      population. A laboratory scale anaerobic horizontal flow filter packed with
      bamboo pieces was evaluated for the treatment of cassava starch extraction
      wastewater. The wastewater used in the experimentation was the draining water of
      the starch sedimentation basin. The reactor was operated for 6 months. It was
      inoculated with a semi-granular sludge from an anaerobic UASB reactor of a
      slaughterhouse. Maximum organic loading rate (OLR) applied was 11.8g COD/L d
      without dilution of the wastewater. At steady state and maximum OLR applied, 87%
      of the COD was removed and a gas productivity of 3.7L/L d was achieved. The
      average biogas yield was 0.36L/g COD removed. Methane content in the biogas was
      in the range of 69-81%. The total suspended solids (TSS) removed were 67%. The
      relative high lactic acid content did not negatively influence the performance of
      the reactor. No perturbation due to cyanide (3-5mg/L) was observed during the
      reactor operation. The results obtained indicated that the anaerobic horizontal
      flow filter could be used efficiently for the treatment of wastewater from
      Colombian starch processing small-scale agroindustry.

PMID- 16973356
TI  - Phytoextraction capacity of the plants growing on tannery sludge dumping sites.
AB  - The study was undertaken to assess the phytoremediation potential of four plants
      (Sida acuta, Ricinus communis, Calotropis procera, Cassia fistula) growing at a
      tannery sludge disposal site. Results showed that maximum amount of K, Fe and Ni
      was associated with residual fraction, whereas, Zn, Mn, Cr, Pb, Cd and Co was
      found in Fe-Mn oxide fraction. Cu and Na were mostly associated with organic
      matter and carbonate fraction, respectively. The results demonstrated that the
      levels of accumulation of metals was found high in all the studied plants and
      followed the order; C. procera>S. acuta>R. communis=C. fistula. The principal
      components analysis (PCA) revealed that translocation behavior of Cu, Zn and Mn,
      Cr were found similar in the plants. Correlation analysis between metal
      accumulation in the plants with DTPA extractable metals emphasized that S. acuta
      and C. fistula provide better value of correlation for most of the tested metals.
      The values of transfer factor were also found high for most of the tested metals
      in the plants of S. acuta. Overall, the plants of S. acuta and C. fistula were
      found suitable for the decontamination of most of the metals from tannery waste
      contaminated sites.

PMID- 16973357
TI  - Treatment of dairy wastewater using constructed wetlands and intermittent sand
      filters.
AB  - In Ireland, the most common method of disposal of dairy parlour washings is by
      land spreading. This treatment method has numerous problems, namely high-labour
      requirements and the potential for eutrophication of surface and ground waters.
      Constructed wetlands are commonly used for treatment of secondary municipal
      wastewaters and they have been gaining popularity for treatment of agricultural
      wastewaters in Ireland. Intermittent sand filtration may offer an alternative to
      traditional treatment methods. As well as providing comparable treatment
      performance, they also have a smaller footprint, due to the substantially higher
      organic loading rates that may be applied to their surfaces. This paper discusses
      the performance and design criteria of constructed wetlands for the treatment of
      domestic and agricultural wastewater, and sand filters for the treatment of
      domestic wastewater. It also proposes sand filtration as an alternative treatment
      mechanism for agricultural wastewater and suggests design guidelines.

PMID- 16973358
TI  - Pyridine-3-propanoic acids: Discovery of dual PPARalpha/gamma agonists as
      antidiabetic agents.
AB  - A series of novel pyridine-3-propanoic acids was synthesized. A structure
      activity relationship study of these compounds led to the identification of
      potent dual PPARalpha/gamma agonists with varied isoform selectivity. Based on
      the results of efficacy studies in diabetic (db/db) mice, and the desired
      pharmacokinetic parameters, compounds (S)-14 and (S)-19 were selected for further
      profiling.

PMID- 16973359
TI  - Inhibition of Tpl2 kinase and TNFalpha production with quinoline-3-carbonitriles
      for the treatment of rheumatoid arthritis.
AB  - The synthesis and structure-activity studies of a series of quinoline-3
      carbonitriles as inhibitors of Tpl2 kinase are described. Potent inhibitors of
      Tpl2 kinase with selectivity against a panel of selected kinases in enzymatic
      assays and specificity in cell-based phosphorylation assays in LPS-treated human
      monocytes were identified. Selected inhibitors with moderate activity in human
      whole blood assay effectively inhibited LPS/D-Gal induced TNFalpha release when
      administered intraperitoneally in mice.

PMID- 16973360
TI  - Structure-activity relationships for a novel series of thiazolyl phenyl ether
      derivatives exhibiting potent and selective acetyl-CoA carboxylase 2 inhibitory
      activity.
AB  - Structure-activity relationships for a recently discovered thiazolyl phenyl ether
      series of acetyl-CoA carboxylase (ACC) inhibitors were investigated. Preliminary
      efforts to optimize the series through modification of the distal aryl ether
      moiety of the lead scaffold resulted in the identification of compounds
      exhibiting low-nanomolar potency and isozyme-selective ACC2 activity.

PMID- 16973361
TI  - Identifying level one patients. A cross-sectional survey on an in-patient
      hospital population.
AB  - The purpose of this study was to identify the characteristics of level one
      patients and to explore how these differed from the other levels of care (zero
      and two). The study was conducted in two parts. Firstly, general adult in
      patients (n=351) on the day of study were classified using the Intensive Care
      Society (ICS) Levels of Care. Secondly, a sample (n=67) of level zero, one and
      two patients were compared using physiological and demographic variables.
      Additionally, each patient was studied using three validated tools: EWS, TISS-28
      and APACHE II. TISS-28 showed statistically significant results (p=0001) when
      correlated to level of care. When all three levels were analysed, EWS (p=0.001),
      APACHE II (p=0.0001) and variance in respiratory rate (p=0.001) showed
      significant differences in score according to level of care. However, no
      statistically significant differences were found between levels zero and one
      using the same data, allowing the deduction that ICS level two criteria are well
      defined and patients easily identifiable. The findings suggest that existing
      measurements of patient acuity, including the ICS criteria, are not sensitive
      enough to differentiate patients 'at risk' of deterioration (level one) from
      normal ward patients (level zero). This also suggests that level zero and one
      patients, based on the ICS classification, may not be from distinct populations
      but, in reality, one homogenous group.

PMID- 16973362
TI  - No deterioration of kinematics and cruciate function 10 years after medial
      unicompartmental arthroplasty.
AB  - The mechanisms of failure for unicompartmental arthroplasty are poorly
      understood. There is some suggestion that long term ligament degeneration,
      particularly of the anterior cruciate ligament (ACL), may affect long term
      survivorship. This study evaluated whether the cruciate mechanism remained
      functional in the long term (10 years) following UKA. Two separate cohorts of
      patients who had undergone St Georg Sled medial compartmental arthroplasty had
      knee kinematics assessed using an established fluoroscopic technique. One group
      (early) was assessed at a mean of 46 months (3.8 years) since surgery, whilst the
      other (late) was assessed at a mean of 125 months (10.4) following surgery. No
      significant difference was found in the sagittal plane kinematics between the two
      groups or in comparison to the control normal knee. The results suggest that
      after fixed bearing UKA the cruciate mechanism remains intact over time and the
      ligaments continue to function similarly to those of the normal knee.

PMID- 16973363
TI  - Surface and biocidal activity of some synthesized metallo azobenzene
      isothiouronium salts.
AB  - A novel series of azobenzene isothiouronium salts of different alkyl chains
      (propyl, hexyl and dodecyl) were synthesized by reaction of 4-((4
      methylphenyl)azo)phenol with 1,3-dibromopropane, 1,6-dibromohexane and 1,12
      dibromododecane, respectively. These salts were reacted with copper (II) halide
      to give their corresponding metallo complexes. The surface tension measurements
      for the synthesized compounds show that the metallo complexes have adsorption and
      micellization better than that of the parent azobenzene isothiouronium salts. The
      pathogenic Gram-negative bacteria, Gram-positive bacteria, fungi and yeast were
      used to determine the biocidal activity of these compounds using gradient plate
      technique. The results indicate that the copper complexes of the synthesized
      azobenzene isothiouronium salts have a relatively better biocidal activity than
      the parent salts.

PMID- 16973364
TI  - Boronic acids as inhibitors of steroid sulfatase.
AB  - Steroid sulfatase (STS) catalyzes the hydrolysis of steroidal sulfates such as
      estrone sulfate (ES1) to the corresponding steroids and inorganic sulfate. STS is
      considered to be a potential target for the development of therapeutics for the
      treatment of steroid-dependent cancers. Two steroidal and two coumarin- and
      chromenone-based boronic acids were synthesized and examined as inhibitors of
      purified STS. The boronic acid analog of estrone sulfate bearing a boronic acid
      moiety at the 3-position in place of the sulfate group was a good competitive STS
      inhibitor with a K(i) of 2.8microM at pH 7.0 and 6.8microM at pH 8.8. The
      inhibition was reversible and kinetic properties corresponding to the mechanism
      for slow-binding inhibitors were not observed. An estradiol derivative bearing a
      boronic acid group at the 3-position and a benzyl group at the 17-position was a
      potent reversible, non-competitive STS inhibitor with a K(i) of 250nM. However,
      its 3-OH analog, a known STS inhibitor, exhibited an almost identical affinity
      for STS and also bound in a non-competitive manner. It is suggested that these
      compounds prefer to bind in a hydrophobic tunnel close to the entrance to the
      active site. The coumarin and chromenone boronic acids were modest inhibitors of
      STS with IC(50)s of 86 and 171microM, respectively. Surprisingly, replacing the
      boronic acid group of the chromenone derivative with an OH group yielded a good
      reversible, mixed type inhibitor with a K(i) of 4.6microM. Overall, these results
      suggest that the boronic acid moiety must be attached to a platform very closely
      resembling a natural substrate in order for it to impart a beneficial effect on
      binding affinity compared to its phenolic analog.

PMID- 16973365
TI  - Synthesis of novel vasodilatory active nicotinate esters with amino acid
      function.
AB  - A variety of N-[(ethyl-4,6-diaryl-3-pyridinecarboxylate)-2-yl]amino acid esters
      6a-h were synthesized through the reaction of 2-bromonicotinates 4 with a number
      of primary amino acid ester hydrochlorides 5 in refluxing tetrahydrofuran in the
      presence of triethylamine as dehydrohalogenating agent. Similarly, reaction of 4
      with N-glycylglycine ethyl ester hydrochloride 7 'as a representative example of
      dipeptide derivative' afforded smoothly the corresponding N-[(ethyl-4,6-diaryl-3
      pyridinecarboxylate)-2-yl]-N'-glycylglycine ethyl ester analogues 8. However,
      reaction of 4 with 5 in refluxing pyridine yielded the unexpected 2
      aminonicotinate esters 9. Vasodilation activity screening for the synthesized
      nicotinate esters was investigated in vitro on the contractile response of
      vascular thoracic aorta smooth muscle from Wistar rats, where all the tested
      compounds exhibit considerable vasodilatory properties. In addition, few prepared
      compounds especially, 6b, 6h and 9b reveal remarkable vasodilation potency
      (IC(50)).

PMID- 16973366
TI  - Facile synthesis of non-steroidal anti-inflammatory active bisbenzamide
      containing compounds.
AB  - A variety of N,N'-bis{2-[1,2-ethanediylbis(oxy-2,1-phenylene)]-1-(substituted
      carbonyl)ethenyl}benzamides 7a-c, 9a-d were synthesized via nucleophilic attack
      of either primary 8 or secondary amines 6 on bisoxazol-5(4H)-one 5. The latter
      was obtained through the reaction of 2,2'-[1,2-ethanediylbis(oxy)]bisbenzaldehyde
      (4) with hippuric acid in acetic anhydride in the presence of anhydrous sodium
      acetate. The anti-inflammatory properties of the prepared compounds were screened
      using carrageenan-induced paw oedema in rats. Many of the prepared bisbenzamide
      containing compounds show considerable in vivo anti-inflammatory activity,
      especially 7b which reveals remarkable pharmacological properties comparable with
      ketoprofen (which was used as a reference standard) at successive time intervals
      (1, 2, 3, 4 and 24h).

PMID- 16973367
TI  - Synthesis and activity of a new class of dual acting norepinephrine and serotonin
      reuptake inhibitors: 3-(1H-indol-1-yl)-3-arylpropan-1-amines.
AB  - Compounds with a combination of norepinephrine and serotonin reuptake inhibition
      have been approved in the US and Europe for a number of indications, including
      major depressive disorder and pain disorders such as diabetic neuropathy and
      fibromyalgia. Efforts to design selective norepinephrine reuptake inhibitors
      based on SAR from the aryloxypropanamine series of monoamine reuptake inhibitors
      have led to the identification of a potent new class of dual acting
      norepinephrine and serotonin reuptake inhibitors, namely the 3-(1H-indol-1-yl)-3
      arylpropan-1-amines.

PMID- 16973368
TI  - Female reproductive system of the sugarcane spittlebug Mahanarva fimbriolata
      (Auchenorrhyncha): vitellogenesis dynamics and protein quantification.
AB  - The present study aimed describing the ovaries of the sugarcane spittlebug
      Mahanarva fimbriolata which are meroistic telotrophic with nurse cells and
      oocytes located in the tropharium. SEM revealed paired ovaries located
      dorsolaterally around the intestine, and oocytes exhibiting shapes ranging from
      round (less developed) to elliptic (more developed), suggesting a simultaneous,
      although, asynchronous development. Based on histological data we classified the
      oocytes in stages from I to V. Stage I oocytes exhibit follicular epithelium with
      cubic and/or prismatic cells, fine cytoplasmic granules. Stage II oocytes present
      intercellular spaces in the follicular epithelium due to the incorporation of
      yolk elements from the hemolymph. Small granules are present in the periphery of
      oocytes while larger granules are observed in the center. Stage III oocytes are
      larger and intercellular spaces in the follicular epithelium are evident, as well
      as the interface between follicular epithelium and oocyte. Yolk granules of
      different sizes are present in the cytoplasm. During this stage, chorion
      deposition initiates. Stage IV oocytes exhibit squamous follicular cells and
      larger intercellular spaces when compared to those observed in the previous
      stage. The oocyte cytoplasm present granular and viscous yolk, the latter is the
      result of the breakdown of granules. Stage V oocytes exhibit a follicular
      epithelium almost completely degenerated, smaller quantities of granular yolk and
      large amounts of viscous yolk. Based on our findings we established the sequence
      of yolk deposition in M. fimbriolata oocyte as follows: proteins and lipids,
      which are first produced by endogenous processes in stages I and II oocytes.
      Exogenous incorporation begins in stage III. In stages I and II oocytes, lipids
      are also produced by follicular epithelial cells. The third element to be
      deposited is polysaccharides, mainly found as complexes. Therefore, the yolk
      present in the oocytes of this species consists of glycolipoproteins. Molecular
      weights of proteins present in M. fimbriolata oocytes ranged from 10 to 92 KDa,
      differently from vitellogenin, the most common protein present in insect oocytes,
      weighing approximately 180 KDa.

PMID- 16973369
TI  - Measurement of the fast neutron flux in the MNSR inner irradiation site.
AB  - The WIMSD4 code was used to calculate the fast neutron flux spectrum and the fast
      neutron fission cross-sections for (238)U, using six energy groups ranging from
      0.5 to 10 MeV. These results, with the measured radioactivities of the (140)Ba,
      (131)I, (103)Ru, (95)Zr and (97)Zr fission products emerging from the fission of
      the (238)U foil covered with a cadmium filter, were used to measure the fast
      neutron flux in the Syrian Miniature Neutron Source Reactor inner irradiation
      site.

PMID- 16973370
TI  - Differential CSF butyrylcholinesterase levels in Alzheimer's disease patients
      with the ApoE epsilon4 allele, in relation to cognitive function and cerebral
      glucose metabolism.
AB  - Butyrylcholinesterase (BuChE) is increased in the cerebral cortex of Alzheimer's
      disease (AD) patients, particularly those carrying epsilon4 allele of the
      apolipoprotein E gene (ApoE) and certain BuChE variants that predict increased AD
      risk and poor response to anticholinesterase therapy. We measured BuChE activity
      and protein level in CSF of eighty mild AD patients in relation to age, gender,
      ApoE epsilon4 genotype, cognition and cerebral glucose metabolism (CMRglc). BuChE
      activity was 23% higher in men than women (p<0.03) and 40-60% higher in ApoE
      epsilon4 negative patients than in those carrying one or two epsilon4 alleles
      (p<0.0004). CSF BuChE level correlated with cortical CMRglc. Patients with high
      to moderate CSF BuChE showed better cognitive function scores than others. We
      hypothesize that CSF BuChE varies inversely with BuChE in cortical amyloid
      plaques. Thus, low BuChE in a patient's CSF may predict extensive incorporation
      in neuritic plaques, increased neurotoxicity and greater central
      neurodegeneration.

PMID- 16973371
TI  - Preparation and biological activity of novel cucurbit[8]uril-fullerene complex.
AB  - The synthesis of a novel cucurbit[8]uril(CB(8))-fullerene[60] supramolecular
      complex using a simple and efficient pathway is reported for the first time. In
      the complex, which was found to be of the 1:2 type, the compounds interact weekly
      with each other. The complex was characterized by UV/Vis, FTIR, elemental
      analysis, X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning
      electron microscopy (SEM), and transmission electron microscopy (TEM). TEM
      analysis shows that the average particle diameter is about 19 nm. The in vitro
      antitumour activity of the complex has been tested and the result shows that the
      complex exhibits better antitumour activity against HeLa cells. The antitumour
      mechanism of the complex was investigated for the first time.

PMID- 16973372
TI  - 5-Aminolaevulinic acid (ALA) induced formation of different fluorescent
      porphyrins: a study of the biosynthesis of porphyrins by bacteria of the human
      digestive tract.
AB  - Aminolaevulinic acid (ALA) induces porphyrin formation in almost all living
      cells. The fluorescence spectra of porphyrins produced from a variety of 31
      bacterial strains from the human oral cavity and other parts of digestive tract
      have been examined. Many of the bacteria exposed to ALA were able to induce
      protoporphyrin IX (PpIX) fluorescence, but under aerobic condition some bacteria
      can also produced different fluorescent porphyrins, in particular water-soluble
      porphyrins that can arise from an oxidation of the corresponding porphyrinogen
      precursors. The formation of fluorescent porphyrins can be different from one
      bacterial strain to another, but also one specific bacterium can form different
      fluorescent porphyrins. Irradiation of the ALA incubated cultures led to a rapid
      formation of water-soluble porphyrins exhibiting fluorescence maxima at
      wavelengths of 618-620 nm. This light induced formation of water-soluble
      porphyrins could be attributed to a photooxidation of the non-fluorescent
      (Uro/Copro)-porphyrinogen precursors. Addition of detergents to some of the
      bacterial cultures led to a strong PpIX fluorescence increase, indicating that
      some of the PpIX originally produced can be present in a non-fluorescent,
      probably aggregated, form. The large abundance of bacteria in the oral cavity and
      other parts of digestive tract, with their capacity to easily produce fluorescent
      porphyrins, indicates that such bacterial fluorescence should be suppressed
      during the ALA-based diagnosis of tumours in order to eliminate false positive
      results.

PMID- 16973373
TI  - Mendelian resistance to human norovirus infections.
AB  - Noroviruses have emerged as a major cause of acute gastroenteritis in humans of
      all ages. Despite high infectivity of the virus and lack of long-term immunity,
      volunteer and authentic studies has suggested the existence of inherited
      protective factors. Recent studies have shown that histo-blood group antigens
      (HBGAs) and in particular secretor status controlled by the
      alpha1,2fucosyltransferase FUT2 gene determine susceptibility to norovirus
      infections, with nonsecretors (FUT2-/-), representing 20% of Europeans, being
      highly resistant to symptomatic infections with major strains of norovirus.
      Moreover, the capsid protein from distinct strains shows different HBGA
      specificities, suggesting a host-pathogen co-evolution driven by carbohydrate
      protein interactions.

PMID- 16973374
TI  - Genetic predisposition to leprosy: A major gene reveals novel pathways of
      immunity to Mycobacterium leprae.
AB  - The elucidation of the genetic control of susceptibility to common infectious
      diseases is expected to provide new and more effective tools for prevention and
      control of some of the most pressings health needs on a global scale. A major
      advantage of whole genome based genetic approaches is that no a priori
      assumptions about mechanisms of pathogenesis need to be made in these studies.
      Hence, genetic studies can identify previously unrecognized pathways of disease
      susceptibility and tag critical pathogenic events for further biochemical,
      immunological or physiological analysis. We have applied this strategy to
      leprosy, a disease that still claims 400,000 new cases each year. We identified
      genetic variants in the shared promoter region of the PARK2 and PACRG genes as
      major risk factors of leprosy susceptibility. Both encoded proteins are part of
      the cellular ubiquitination system. Specifically, PARK2, the cause of early onset
      Parkinson's disease, is an E3 ligase that likely is involved in controlled
      proteolysis, the cellular anti-oxidants response and the regulation of innate
      immune responsiveness. In addition, numerous E3 ligases have recently been shown
      to be critical regulators of immunity. While the specific role of PARK2/PACRG in
      leprosy pathogenesis remains unknown, a number of experimentally testable
      scenarios can be developed to further explore the role of these proteins in anti
      Mycobacterium leprae host responsiveness.

PMID- 16973375
TI  - Description of HLA class I- and CD8-deficient patients: Insights into the
      function of cytotoxic T lymphocytes and NK cells in host defense.
AB  - Over the last few years, several patients with defects in the HLA class I
      presentation pathway have been described. Analysis of their clinical symptoms and
      immunological parameters have led to the identification of several unexpected
      findings which are of importance to understand the role of HLA class I-dependent
      immune responses in host defense. Here, we will describe and compare clinical
      manifestations and immunological findings of patients with defects in the peptide
      transporter proteins (TAP complex), tapasin and CD8 molecules.

PMID- 16973376
TI  - Heterologous expression and purification of kynurenine-3-monooxygenase from
      Pseudomonas fluorescens strain 17400.
AB  - Kynurenine 3-monooxygenase (KMO) is an NADPH-dependent flavoprotein hydroxylase
      that catalyzes the conversion of l-Kynurenine (L-Kyn) to 3-hydroxykynurenine
      (3OHKyn). The reaction is central to the tryptophan degradative pathway and takes
      place within microglial cells defining cellular concentrations of the N-methyl-d
      aspatate (NMDA) receptor agonist quinolinate and antagonist kynurenate. The
      influence over the cellular concentrations of these NMDA receptor effectors makes
      KMO an attractive target for the treatment of ischemic stroke. Pseudomonas
      fluorescens str 17400, expresses five activities of tryptophan catabolism
      including that of KMO. The KMO gene from P. fluorescens was cloned into the pET
      17b plasmid using incorporated NdeI and XhoI restriction sites. This construct
      yielded PfKMO to 20% of total cell protein after 12h of expression at 22 degrees
      C without induction by isopropyl-beta-thiogalactopyranoside (IPTG). The enzyme
      could be readily purified using ammonium sulfate fractionation and ion exchange
      chromatography, resulting in pure KMO with a turnover number of 5.0 s(-1). PfKMO
      activity was dependent on the reduction state of the enzyme. Preparation and
      storage benefited from the presence of a reductant such as dithiothreitol or beta
      mercaptoethanol. The loss of activity was found to be directly related to the
      oxidation of thiols as measured by dinitrothiobenzoate assay. Steady-state assays
      monitoring the consumption of dioxygen were used to measure apparent kinetic
      parameters and ligand perturbation of flavin fluorescence was used to determine a
      Kd value for both L-Kyn and the inhibitor m-nitrobenzoylalanine. PfKMO is offered
      as prototypical bacterial form of the enzyme to serve as a viable platform on
      which to base future KMO studies.

PMID- 16973377
TI  - Recombinant expression, purification, and kinetic and inhibitor characterisation
      of human site-1-protease.
AB  - Human site-1-protease (S1P, MEROPS S08.8063), also widely known as
      subtilisin/kexin isozyme 1 (SKI-1), is a membrane bound subtilisin-related serine
      protease, that belongs to a group of nine mammalian proprotein convertases. Among
      these proteases, S1P displays unique substrate specificity, by showing preferred
      cleavage after non-basic amino acids. S1P plays a key role in a proteolytic
      pathway that controls the cholesterol content of membranes, cells and blood. S1P
      also participates in the activation of viral coat glycoproteins of the lassa
      virus, the lympocytic choriomeningitis virus and the crimean congo hemorrhagic
      fever virus. We expressed recombinant human S1P using the baculovirus expression
      vector system and characterized the highly purified enzyme. Featuring a new
      chromogenic substrate (Acetyl-Arg-Arg-Leu-Leu-p-nitroanilide) we show that the
      enzymatic activity of S1P is not calcium dependent, but can be modulated by a
      variety of mono- and divalent cations. S1P displayed pronounced positive
      cooperativity with a substrate derived from the viral coat glycoprotein of the
      lassa virus. The screening of a limited number of protease inhibitors showed that
      S1P was not inhibited by specific inhibitors of other proprotein convertases or
      by Pefabloc SC (4-(2-aminoethyl) benzene sulphonyl fluoride, AEBSF). We found 3,4
      dichloroisocoumarin (DCI) to be a potent slow binding inhibitor of human S1P,
      with a K(iapp) = 6.8 microM, thus representing a new small molecule inhibitor of
      S1P. These findings show that S1P differs significantly from other proprotein
      convertases with respect to kinetics, co-factor requirement and inhibition.

PMID- 16973378
TI  - Expression, purification, and characterization of stable, recombinant human
      adenylosuccinate lyase.
AB  - The full length human adenylosuccinate lyase gene was generated by a PCR method
      using a plasmid encoding a truncated human enzyme as template, and was cloned
      into a pET-14b vector. Human adenylosuccinate lyase was overexpressed in
      Escherichia coli Rosetta 2(DE3)pLysS as an N-terminal histidine-tagged protein
      and was purified to homogeneity by a nickel-nitriloacetic acid column at room
      temperature. The histidine tag was removed from the human enzyme by thrombin
      digestion and the adenylosuccinate lyase was purified by Sephadex G-100 gel
      filtration. The histidine-tagged and non-tagged adenylosuccinate lyases exhibit
      similar values of Vmax and Km for S-AMP. Analytical ultracentrifugation and
      circular dichroism revealed, respectively, that the histidine-tagged enzyme is in
      tetrameric form with a molecular weight of 220 kDa and contains predominantly
      alpha-helical structure. This is the first purification procedure to yield a
      stable form of human adenylosuccinate lyase. The enzyme is stable for at least 5
      days at 25 degrees C, and upon rapid freezing and thawing. Temperature as well as
      reducing agent (DTT) play critical roles in determining the stability of the
      human adenylosuccinate lyase.

PMID- 16973379
TI  - 3D reconstruction and processing of volumetric data in cryo-electron tomography.
AB  - A software package is presented that was primarily developed for electron
      tomography in biological research. It comprises routines for preprocessing
      micrographs, CTF-correction of images of untilted and tilted specimens, alignment
      of tilt series, 3D reconstruction, spatial averaging of paracrystalline
      specimens, alignment of single particles or components of larger macromolecular
      assemblies, correlation averaging, multivariate statistical analysis,
      classification, and volume reassembly, in which molecular components in raw
      tomograms are replaced by averaged versions with higher signal-to-noise ratio.
      The emphasis for image analysis is placed on the processing of large sets of
      individual molecular volumes. The design philosophy of the software is both
      simplicity and interoperability, i.e. to write standalone programs for simple
      tasks that are combined through shell scripting to provide more complex
      functionality, and to communicate with other software via common image formats.
      This paper gives an overview of the current state of the programs and some
      applications to cryo-electron tomography.

PMID- 16973380
TI  - A simulation method for the firing sequences of motor units.
AB  - The firing sequences of motoneurons contain important information with regard to
      the underlying neural processes. Several methods have been proposed in the
      literature to simulate these sequences, however, one of the limitations is that
      they are not capable of simulating the complex neural dynamics of motor neurons,
      especially those of concurrently active ones, such as motor unit synchrony and
      motor unit common drive. In this paper, a novel model based on the Hodgkin-Huxley
      (HH) system is proposed, which has the ability to simulate the complex
      neurodynamics of the firing sequences of motor neurons. The model is presented at
      the cellular level and network level, and some simulation results from a simple 3
      neuron network are presented to demonstrate its applications.

PMID- 16973381
TI  - Tracking of systemically administered mononuclear cells in the ischemic brain by
      high-field magnetic resonance imaging.
AB  - This study was designed to track systemically administered mononuclear cells
      (MNCs) in the ischemic mouse brain using 7 T magnetic resonance imaging (MRI).
      Splenectomized wild-type mice were subjected to brain ischemia by 30 or 60 min
      filamentous occlusion of the middle cerebral artery (MCAo) and reperfusion.
      Spleen-derived MNCs were labeled with very small superparamagnetic iron-oxide
      particles (VSOP) and transfused into recipient mice 30 min, 8 h, or 24 h after
      MCAo via the tail vein. High-resolution MRI sequences were designed to monitor
      the dynamics of brain ischemia and to observe the migration and engraftment of
      transfused cells into the ischemic brain. T2*-weighted (gradient-echo)
      hypointense signal changes became apparent at 24-48 h after transfusion, were
      typically associated with the ischemic lesion border, and could be followed up to
      5 weeks after the insult. Such presumed MNC-associated signal changes in MRI were
      confirmed by histochemical detection of iron (Prussian blue staining) and
      detection of constitutively expressed green fluorescent protein (GFP) in a subset
      of animals transfused with MNCs derived from GFP transgenic mice. Taken together,
      our results demonstrate that brain engraftment of systemically administered
      mononuclear cells can be visualized non-invasively over time and space using high
      resolution MRI.

PMID- 16973382
TI  - A neural network reflecting individual differences in cognitive processing of
      emotions during perceptual decision making.
AB  - Even simple perceptual decisions are influenced by the emotional content of a
      stimulus. Recent neuroimaging studies provide evidence about the neural
      mechanisms of perceptual decision making on emotional stimuli. However, the
      effect of individual differences in cognitive processing of emotions on
      perceptual decision making remains poorly understood. Here, we investigated how
      changes in the fMRI signal during perceptual decision making on facial stimuli
      covaried with individual differences in the ability to identify and communicate
      one's emotional state. Although this personality trait covaried with changes in
      activity in the dorsal anterior cingulate cortex (dACC) during gender decisions
      on facial expressions, there was no correlation during emotion decisions.
      Further, we investigated whether individual differences in the ability to
      cognitively process emotions depend on differences in the functional integration
      of emotional and cognitive brain regions. We therefore compared task-dependent
      changes in effective connectivity of dACC in individuals with good and with poor
      ability to cognitively process emotions using a psychophysiological interaction
      analysis. We found greater coupling of dACC with prefrontal regions in
      individuals with good ability to identify and communicate their emotional state.
      Conversely, individuals with poor ability in this domain showed greater coupling
      of dACC with the amygdala. Our data indicate that individual differences in the
      ability to identify and communicate one's emotional state are reflected by
      altered effective connectivity of the dACC with prefrontal and limbic regions.
      Thus, we provide neurophysiological evidence for a theoretical model that posits
      that a discommunication between limbic areas and the neocortex impairs cognitive
      processing of emotions.

PMID- 16973383
TI  - Topiramate treatment for nocturnal frontal lobe epilepsy.
AB  - PURPOSE: Aim of this study was to evaluate the efficacy and tolerability of the
      antiepileptic drug topiramate (TPM) in a sample of patients with nocturnal
      frontal lobe epilepsy (NFLE). METHODS: A 24 patients with video
      polysomnographically confirmed NFLE received topiramate as single or add-on
      therapy. They all completed diaries concerning the seizures frequency and
      complexity and underwent to periodic follow-up visits. We classified the patients
      as: seizure-free, responders or non-responders. RESULTS: 15 M; 9 F; mean age
      29.3+/-10.4 years. The video-polysomnographic recordings showed a wide spectrum
      of seizures, ranging from repeated stereotypic brief motor attacks to prolonged
      attacks, with complex and bizarre behaviour; the recorded episodes occurred
      during non-REM sleep, both stage 2 and stage 3-4. The EEG during wakefulness was
      normal in all the patients, while seven of them showed epileptiform abnormalities
      during polysomnography. TPM was administered as single or add-on therapy from 50
      to 300mg daily at bedtime. The follow-up duration ranged from 6 months to 6
      years. The patients were classified as: seizure-free=6 (25%); responders
      (reduction of at least 50% of seizures)=15 (62.5%); non-responders=3 (12.5%). The
      adverse events were: weight loss (6 pts, 25%); paresthesias (3 pts, 12.5%);
      speech dysfunction (2 pts, 8.3%). All the adverse events disappeared within 3
      months. CONCLUSIONS: In our experience, TPM seems to be effective in about 90% of
      patients with NFLE. Few of them experienced transitory adverse events. TPM could
      be included in the options for patients with this form of epilepsy.

PMID- 16973384
TI  - Aggressiveness and memory: subordinate crabs present higher memory ability than
      dominants after an agonistic experience.
AB  - A relationship between aggressiveness and memory has been proposed in several
      studies with different animal species. Here, we study this possibility in the
      crab Chasmagnathus granulatus, using the context-signal memory model (CSM) that
      involves an association between the learning context and a visual danger
      stimulus. Each experiment consisted of an agonistic phase and a memory one.
      During the former, matched pairs of male crabs were staged in two 10-min
      encounters and the dominant or subordinate condition of each member of the dyad
      was determined. During the memory phase, crabs were trained to acquire CSM and
      tested 24 h later. Results showed that the agonistic encounter, staged 48 h
      before the acquisition of CSM, can modulate memory according to the dominance
      condition of the fighter; in such a way that memory retention of subordinates
      results higher than that of dominants. By contrast, when the memory phase
      preceded the agonist one, forthcoming dominants and subordinates did not differ
      in their memory ability. The memory modulation would not be linked to a dominance
      status but to a persistent dominance relationship fully reconstructed in each
      encounter between the same opponents. Therefore, the crab's CSM would not depend
      directly on predetermined intrinsic properties, but on the outcome of the fight,
      which would be determined in turn by the relative aggressiveness of the fighters.
      The finding that the agonistic episode modulates memory opens the possibility of
      using this episodic interference to probe the function of diverse phases of CSM.

PMID- 16973385
TI  - Dynamic programming of CD8+ T cell trafficking after live viral immunization.
AB  - After viral infection, activated T cells are present in multiple tissues
      regardless of the infection route. How these cells acquire pleiotropic homing
      ability is unclear. By using a cutaneous vaccinia virus infection model, we
      demonstrate that regulation of T cell trafficking is multiphasic. Upon completion
      of three cell divisions, CD8+ T cells upregulated specific skin-homing molecules
      within draining lymph nodes (LN). By 60 hr after infection, some activated T
      cells reached the infected tissue, while others entered distant antigen-free LN.
      These latter cells continued to divide and acquire additional tissue-homing
      molecules in this new setting, independent of antigen presentation. After viral
      clearance, the initial skin-homing imprint became the predominant homing
      phenotype on memory cells and provided superior protection against secondary
      cutaneous challenge. These observations demonstrate a mechanism by which T cells
      provide both immediate tissue-specific immune control at the pathogen entry site
      and a more flexible systemic protection against pathogen dissemination.

PMID- 16973386
TI  - Transforming growth factor-beta controls development, homeostasis, and tolerance
      of T cells by regulatory T cell-dependent and -independent mechanisms.
AB  - The role of transforming growth factor-beta (TGF-beta) in inhibiting T cell
      functions has been studied with dominant-negative TGF-beta receptor transgenic
      models; however, the full impact of TGF-beta signaling on T cells and the
      mechanisms by which TGF-beta signals remain poorly understood. Here we show that
      mice with T cell-specific deletion of TGF-beta receptor II developed lethal
      inflammation associated with T cell activation and differentiation. In addition,
      TGF-beta signaling positively regulated T cell development and homeostasis.
      Development of CD8+ T cells and NKT cells, maintenance of peripheral Foxp3
      expressing regulatory T cells, and survival of CD4+ T cells all depended on TGF
      beta signaling. Both T helper 1 (Th1) differentiation and survival of activated
      CD4+ T cells required T-bet, the TGF-beta-regulated transcription factor, which
      controlled CD122 expression and IL-15 signaling in Th1 cells. This study reveals
      pleiotropic functions of TGF-beta signaling in T cells that may ensure a diverse
      and self-tolerant T cell repertoire in vivo.

PMID- 16973387
TI  - Cellular mechanisms of fatal early-onset autoimmunity in mice with the T cell
      specific targeting of transforming growth factor-beta receptor.
AB  - Transforming growth factor-beta (TGF-beta) has been implicated in the control of
      differentiation and proliferation of multiple cell types. However, a role for TGF
      beta in the control of immune homeostasis is not fully understood because of its
      pleiotropic action. Here we report that complete ablation of the TGF-beta
      signaling in T cells engendered aggressive early-onset, multiorgan, autoimmune
      associated lesions with 100% mortality. Peripheral CD4+ and CD8+ T cells with TGF
      beta-receptor II (TGF-betaRII) deficiency activated cytolytic and T helper 1
      (Th1) differentiation program in a cell-intrinsic T cell receptor (TCR)-specific
      fashion. Furthermore, TGF-betaRII deficiency blocked the development of canonical
      CD1d-restricted NKT cells. Instead, it facilitated generation of a highly
      pathogenic T cell subset exhibiting multiple hallmarks of NK cells and sharply
      elevated amounts of FasL, perforin, granzymes, and interferon-gamma. Thus, TGF
      beta signaling in peripheral T cells is crucial in restraining TCR activation
      dependent Th1, cytotoxic, and NK cell-like differentiation program which, when
      left unchecked, leads to rapidly progressing fatal autoimmunity.

PMID- 16973388
TI  - Toll-like receptor 7-dependent loss of B cell tolerance in pathogenic
      autoantibody knockin mice.
AB  - Systemic lupus erythematosus (SLE) is characterized by the production of
      autoantibodies that are frequently directed against nucleic acid-associated
      antigens. To better understand how B cells reactive with such antigens are
      regulated, we generated a model system in which heavy and light chain genes
      encoding 564 immunoglobulin have been targeted to the heavy and light chain loci
      of the nonautoimmune C57BL/6 mouse strain. This antibody recognizes RNA, single
      stranded DNA, and nucleosomes. We show that B cells expressing this
      immunoglobulin were activated, producing class-switched autoantibody in vivo
      despite the apparently normal induction of anergy. This autoantibody production
      was largely dependent on Toll-like receptor 7 (TLR7). We further show that
      production of these autoantibodies was sufficient to cause kidney pathology in
      these mice. These results demonstrate that the particular threat of nucleic acid
      containing autoantigens lies in their ability to bind both antigen receptor and
      TLR7.

PMID- 16973389
TI  - Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing
      inflammatory and regulatory roles in a murine model of lupus.
AB  - Antibodies (Abs) to RNA- and DNA-containing autoantigens are characteristic of
      systemic lupus erythematosus (SLE). We showed previously that Toll-like receptor
      (TLR) 9, recognizing DNA, is required for the spontaneous generation of DNA
      autoantibodies, but not for the development of lupus nephritis in susceptible
      mice. We report that lupus-prone mice deficient in TLR7, a receptor for ssRNA,
      failed to generate Abs to RNA-containing antigens (Ags) such as Smith (Sm) Ag.
      TLR9 and TLR7 also had dramatic effects on clinical disease in lupus-prone mice.
      In the absence of TLR9, autoimmune disease was exacerbated, lymphocytes and
      plasmacytoid DCs were more activated, and serum IgG and IFN-alpha were increased.
      In contrast, TLR7-deficient mice had ameliorated disease, decreased lymphocyte
      activation, and decreased serum IgG. These findings reveal opposing inflammatory
      and regulatory roles for TLR7 and TLR9, despite similar tissue expression and
      signaling pathways. These results have important implications for TLR-directed
      therapy of autoimmune disease.

PMID- 16973390
TI  - Alternative and classical NF-kappa B signaling retain autoreactive B cells in the
      splenic marginal zone and result in lupus-like disease.
AB  - Expression of B cell-activating factor (BAFF), a critical B cell survival factor,
      is elevated in autoimmune and lymphoproliferative disorders. Mice overproducing
      BAFF develop systemic lupus erythematosus (SLE)-like disease and exhibit B cell
      activation of classical and alternative NF-kappaB-signaling pathways. We used a
      genetic approach and found that both NF-kappaB-signaling pathways contributed to
      disease development but act through distinct mechanisms. Whereas BAFF enhanced
      long-term B cell survival primarily through the alternative, but not the
      classical, NF-kappaB pathway, it promoted immunoglobulin class switching and
      generation of pathogenic antibodies through the classical pathway. Activation of
      the alternative NF-kappaB pathway resulted in integrin upregulation, thereby
      retaining autoreactive B cells in the splenic marginal zone, a compartment that
      contributes to their survival. Thus, both classical and alternative NF-kappaB
      signaling are important for development of lupus-like disease associated with
      BAFF overproduction. The same mechanisms may be involved in the pathogenesis of
      human SLE.

PMID- 16973391
TI  - Prebiotic effects of neoagaro-oligosaccharides prepared by enzymatic hydrolysis
      of agarose.
AB  - To investigate the prebiotic properties of neoagaro-oligosaccharides (NAOS),
      obtained from enzymatic hydrolysis of agarose, the in vitro and in vivo effects
      of NAOS on bacterial growth were studied. In vitro NAOS were found to be highly
      resistant to enzymes of the upper gastrointestinal tract, which remained intact
      after 24h incubation with different amylolytic enzymes. NAOS significantly
      stimulated the growth of bifidobacteria and lactobacilli in Man-Rogosa-Sharp
      (MRS) medium, anaerobically. Compared with fructo-oligosaccharides (FOS), 1%
      (w/v) NAOS promoted the specific growth rate of beneficial bacteria by about
      100%. The decreases of media pH with NAOS were almost the same as that with FOS.
      In vivo, NAOS significantly increased the numbers of lactobacilli and
      bifidobacteria (P<0.05) in fresh feces or cecal content while reducing
      putrefactive microorganisms. Mice fed with 2.5% (w/v) NAOS for 7 days had larger
      increases in colonic beneficial bacteria population than those fed with even 5%
      (w/v) FOS for 14 days. No side effects, such as eructation and bloating, were
      found. Interestingly, NAOS with higher degrees of polymerization (DP) showed
      better prebiotic activity. These results indicated that NAOS had great prebiotic
      effect, which could be beneficial to the host.

PMID- 16973392
TI  - The brain's master circadian clock: implications and opportunities for therapy of
      sleep disorders.
AB  - The suprachiasmatic nuclei (SCN) residing in the anterior hypothalamus maintains
      a near-24-h rhythm of electrical activity, even in the absence of environmental
      cues. This circadian rhythm is generated by intrinsic molecular mechanisms in the
      neurons of the SCN; however, the circadian clock is modulated by a wide variety
      of influences, including glutamate and pituitary adenylate cyclase-activating
      peptide (PACAP) from the retinohypothalamic tract, melatonin from the pineal
      gland, and neuropeptide Y from the intergeniculate leaflet. By virtue of these
      and other inputs, the SCN responds to environmental cues such as light, social
      and physical activities. In turn, the SCN controls or influences a wide variety
      of physiologic and behavioral functions, including attention, endocrine cycles,
      body temperature, melatonin secretion, and the sleep-wake cycle. Regulation of
      the sleep-wake cycle by the SCN has important implications for development of
      therapies for sleep disorders, including those involving desynchronization of
      circadian rhythms and insomnia.

PMID- 16973393
TI  - Metabolic response to cooling temperatures in chicken embryos and hatchlings
      after cold incubation.
AB  - We asked to what extent cold exposure during embryonic growth, and the
      accompanying hypometabolism, may interfere with the normal development of
      thermogenesis. White Leghorn chicken eggs were incubated in control conditions
      (38 degrees C) or at 36 or 35 degrees C. Embryos incubated at a lower temperature
      (34 degrees C) failed to hatch. The cold-incubated embryos had lower oxygen
      consumption (VO2) and body weight (W) throughout incubation, and hatching was
      delayed by about, respectively, 1 and 2 days. The W-VO2 relationship of the cold
      incubated embryos was as in controls, indicating that cold-induced hypometabolism
      was at the expense of the growth, not the maintenance, component of VO2. At
      embryonic day E11, the metabolic response to changes in ambient temperature (T)
      over the 30-39 degrees C range was typically poikilothermic, with Q10 = 1.8-1.9,
      and similar among all sets of embryos. Toward the end of incubation (E20), the
      thermogenic responses of the cold-incubated embryos were significantly lower than
      in controls. This difference occurred also in the few-hour old hatchlings (H1),
      even though, at this time, W was similar among groups. Exposure to cold during
      only the last 3 days of incubation (from E18 to H1), i.e. during the
      developmental onset of the endothermic mechanisms, did not lower the thermogenic
      capacity of the hatchlings. In conclusion, sustained cold-induced hypometabolism
      throughout incubation blunted the rate of embryonic growth and the development of
      thermogenesis. This latter phenomenon could be an example of epigenetic
      regulation, i.e. of environmental factors exerting a long-term effect on gene
      expression.

PMID- 16973394
TI  - [Micrometastatic disease and residual axillary disease. Breast cancer as an
      example Alct].
AB  - The knowledge of the axillary involvement is a major prognosis factor for breast
      cancer and an important parameter for treatment decision. Nevertheless, two
      recent current medical situations have occurred in breast cancer, changing our
      management. First, with the development of mass screening and sentinel lymph
      nodes biopsies, we have to take treatment decisions based upon minimal lymph node
      involvement, with a clinical significance still poorly understood. Second, for
      the large tumors, potentially with lymph node involvement, we have to deal with
      tumor and lymph node under staging, after induction chemotherapy. We have to
      learn how to evaluate accurately those new parameters to treat the best way our
      patients.

PMID- 16973396
TI  - Both TLR2 and TLR4 are involved in the recognition of Candida albicans. Reply to
      "TLR2, but not TLR4, triggers cytokine production by murine cells in response to
      Candida albicans yeasts and hyphae" by Gil and Gozalbo, Microbes and Infection 8
      (2006) 2823-2824.

PMID- 16973397
TI  - [How to improve IVF results from a clinical point of view?].
AB  - This study reports the last data of the literature on the possibilities of
      optimizing chances of pregnancy during in vitro fertilization attempts, our
      research concerning only the clinical point of view while excluding biologic
      possibilities. The selection of the patients, the management of controlled
      ovarian hyperstimulation protocols, the optimalisation of the transfer and the
      luteal phase support will be cross-reviewed.

PMID- 16973399
TI  - [Cigarette smoking and fertility in women and men].
AB  - Cigarette smoking consequences on female and male reproduction have been
      evaluated for twenty years only and thus poorly spread in the general population.
      However, several studies have noticed noxious effects of tobacco before and after
      conception, in both women and men, from smokers gametes to their offspring. This
      negative impact occurs in spontaneous as well as in assisted reproduction (ART).
      For women, pregnancy rate is decreased, early spontaneous abortions are increased
      and ovarian reserve is altered. For men, standard sperm parameters are modified
      and spermatozoon nuclear quality is compromised. One of the mechanisms involved
      in those anomalies could be the oxidative stress produced by some cigarette
      smoking components. The consequences on smokers offspring are hardly evaluated
      yet: pathologies of the respiratory system, decrease of fecundity and cancers
      outcomes. In conclusion, it seems obvious that smokers - men as women - have to
      quit smoking before having a parental project.

PMID- 16973400
TI  - Measurement of lumbar multifidus muscle contraction with rehabilitative
      ultrasound imaging.
AB  - Rehabilitative Ultrasound Imaging (RUSI) has been validated as a noninvasive
      method to measure activation of selected muscles. The purpose of this study was
      to determine the relationship between muscle thickness change, as measured by
      ultrasonography, and electromyography (EMG) activity of the lumbar multifidus
      (LM) muscle in normal subjects. Bipolar fine wire electrodes were inserted into
      the LM at the L4 level of five subjects. Simultaneous EMG and RUSI data (muscle
      thickness) were collected while subjects performed increasingly demanding
      postural response tasks thought to activate the LM muscle. To determine the
      relationship between muscle thickness change and EMG activity, the normalized EMG
      data were correlated to normalized RUSI data. To determine if the tasks increased
      the demand on the LM, the mean EMG data were compared over each of the four
      tasks. Muscle thickness change as measured by RUSI was highly correlated with EMG
      activity of LM in asymptomatic subjects (r=.79,P<.001). Mean EMG data showed
      increasing levels of activation across tasks (19-34% of maximum voluntary
      isometric contraction (MVIC)). The results of the repeated measures ANOVA
      demonstrated theses differences were significant (F(3,12)=25.39,P<.001).
      Measurement of muscle thickness change utilizing RUSI is a valid and potentially
      useful method to measure activation of the LM muscle in a narrow range (19-34% of
      MVIC) in an asymptomatic population.

PMID- 16973401
TI  - Strain on the repaired supraspinatus tendon during manual traction and
      translational glide mobilization on the glenohumeral joint: a cadaveric
      biomechanics study.
AB  - There has been no report on the mechanical effects of joint mobilization on
      rotator cuffs. The purpose of this study was to determine whether it is safe to
      use grade 3 joint mobilization techniques after rotator cuff repair. Nine fresh
      frozen cadaveric shoulders were used in this study. The strains on the
      artificially repaired supraspinatus tendon during joint mobilization were
      measured at 0 degrees and 30 degrees of shoulder abduction and were compared with
      those at the maximal stretching position and relaxing position. Additionally, gap
      distances were measured during this experiment. The strain at 30 degrees of
      abduction of the repaired tendon during each joint mobilization was significantly
      smaller than that at 0 degrees abduction (P<0.05). At 30 degrees of abduction,
      the strain during joint mobilization was not statistically different from that of
      the shoulder in the relaxing position, except during the inferior glide
      technique. Gap distances were 0mm at 30 degrees , while the distances were 1.06
      1.46 mm at 0 degrees. Our findings suggest that joint mobilization techniques,
      except inferior glide, can be performed safely without significantly straining
      the repaired tendon at 30 degrees of abduction, if rotator cuff repair is
      performed at 0 degrees of abduction.

PMID- 16973402
TI  - The use of surface electromyography as a tool in differentiating
      temporomandibular disorders from neck disorders.
AB  - The aim of this study was to assess the electromyographic characteristics of the
      masticatory muscles (masseter and temporalis) of patients with either
      "temporomandibular joint disorder" or "neck pain". Surface electromyography of
      the right and left masseter and temporalis muscles was performed during maximum
      teeth clenching in 38 patients aged 21-67 years who had either (a)
      temporomandibular joint disorder (24 patients); (b) "neck pain" (13 patients).
      Ninety-five control, healthy subjects were also examined. During clenching,
      standardized total muscle activities (electromyographic potentials over time)
      were significantly different in the three groups: 75 microV/microVs% in the
      temporomandibular joint disorder patients, 124 microV/microVs% in the neck pain
      patients, and 95 microV/microVs% in the control subjects (analysis of variance,
      P<0.001). The temporomandibular joint disorder patients also had significantly
      (P<0.001) more asymmetric muscle potentials (78%) than either neck pain patients
      (87%) or control subjects (92%). A linear discriminant function analysis allowed
      a significant separation between the two patient groups, with a single patient
      error of 18.2%. Surface electromyographic analysis during clenching allowed to
      differentiate between patients with a temporomandibular joint disorder and
      patients with a neck pain problem.

PMID- 16973403
TI  - Accuracy and reliability of observational motion analysis in identifying shoulder
      symptoms.
AB  - INTRODUCTION: Aberrations in shoulder movement patterns are believed to be
      associated with the presence of shoulder symptoms. However, the detection of
      movement aberrations has not been rigorously investigated. It is possible that
      manipulative physiotherapists use the clinical history to prejudge the existence
      of aberrations, rather than the actual observation of the movement pattern
      itself. There is a need to determine whether physiotherapists, in the absence of
      a clinical history, can relate observed anomalies of shoulder movement to the
      presence of symptoms and to determine the reliability for observation of such
      anomalous shoulder movement. METHODS: The sample comprised of 9 symptomatic
      subjects recruited from four physiotherapy clinics in Christchurch, New Zealand
      and a further 11 asymptomatic subjects recruited from Christchurch's general
      population. They were videotaped performing shoulder flexion, abduction, and
      scapular plane abduction. The video-recordings were evaluated by 11 manipulative
      physiotherapists who did not know which subjects were symptomatic and who were
      thus required to judge the symptomatic status as: asymptomatic, symptomatic left,
      symptomatic right or symptomatic both. Additionally, each physiotherapist
      completed a survey on each of the 20 subjects regarding the type of movement
      anomaly that was perceived (e.g. too much scapular elevation, too little
      glenohumeral movement, etc). Classification accuracy (percentage of correct
      responses) and agreement (kappa) among physiotherapists were computed. RESULTS:
      Out of the 220 responses by the physiotherapists regarding symptomatic status,
      58% were correct, with 68% asymptomatic, 71% symptomatic left and 30% symptomatic
      right subjects correctly classified. Reliability analysis showed kappa statistics
      for all subjects was 0.23, for asymptomatic subjects 0.22, symptomatic left 0.34,
      and symptomatic right 0.17. Only five subjects had two or more evaluators agree
      on the type of anomalous movement. CONCLUSIONS: Although movement analysis is
      considered an integral part of a physiotherapist's skill this research has shown
      that a sample of experienced manipulative physiotherapists had difficulty in
      determining the symptomatic status of patients with clinically diagnosed shoulder
      complaints by movement analysis alone.

PMID- 16973404
TI  - Visions for novel biophysical elucidations of extracellular matrix networks.
AB  - The extracellular matrix consists of multifunctional molecules, which are
      composed of a large numbers of different domains. Clearly these domains and even
      the entire molecules do not function independently as isolated species, but
      interact with each other in large networks. In many cases specific regions of the
      networks may be considered as molecular machines in which the different molecules
      are arranged in highly defined spatial structures and act in a dynamic, concerted
      fashion. At present most structural information is limited to single molecules,
      and dynamics have been measured mainly for pairs of interacting partners in
      solution. Work needs to be extended to large integrated systems and the functions
      of molecular machines need to be explored. Electron tomography, fluorescence
      resonance energy transfer, and other biophysical techniques are very promising.

PMID- 16973405
TI  - Functional expression of CXC chemokine recepter-4 mediates the secretion of
      matrix metalloproteinases from mouse hepatocarcinoma cell lines with different
      lymphatic metastasis ability.
AB  - CXC chemokine recepter-4 (CXCR4) and its ligand, stromal cell-derived factor
      1alpha (SDF-1alpha) have been implicated in the organ-specific metastasis of
      several malignancies. Hca-F and its syngeneic cell line Hca-P are mouse
      hepatocarcinoma cell lines with high and low potential of lymphatic metastasis,
      respectively. Previous studies showed that the secretion of matrix
      metalloproteinases (MMPs) associated with the metastatic ability of Hca-F and Hca
      P cell line depending on the lymph node environment. However, the mechanism of
      this process has remained unclear. This study investigated the roles of CXCR4 on
      Hca-F cell and SDF-1alpha of lymph node in lymphatic metastasis. The RT-PCR and
      Flow cytometry analysis results show that Hca-F cells express higher level CXCR4
      mRNA and cell-surface CXCR4 protein, as compared with Hca-P cells. Treatment of
      recombinant SDF-1alpha proteins induced greater amount of calcium-flux in Hca-F
      cells than that in Hca-P cells, demonstrating higher functional CXCR4 expression
      on Hca-F cells than that on Hca-P cells. Furthermore, both the cell-free extratcs
      of lymph node and recombinant SDF-1alpha proteins induced secretions of active
      MMP-9 and MMP-2 from Hca-F cells in vitro. But those secretions were
      significantly reduced by blockade of cell surface CXCR4 with rabbit anti-mouse
      CXCR4 polyclonal antibody (pAb) and neutralization of SDF-1alpha in lymph node
      extracts with rabbit anti-mouse SDF-1alpha pAb as well. These results suggest
      that the CXCR4/SDF-1alpha system mediates active MMP-9 and MMP-2 secretion from
      Hca-F and Hca-P cells, which facilitates lymphogenous metastasis of those cells
      consequently.

PMID- 16973406
TI  - Role of the phosphatidylinositol 3-kinase and mTOR pathways in the regulation of
      renal fibroblast function and differentiation.
AB  - Tubulointerstitial fibrosis is largely mediated by (myo)fibroblasts present in
      the interstitium. In this study, we investigated the role of mTOR and
      phosphatidylinositol 3-kinase in the regulation of fibroblast kinetics,
      fibroblast differentiation, and collagen synthesis. Rat renal fibroblasts were
      propagated from kidneys 3 days post-ureteric obstruction and specific inhibitors
      of mTOR (RAD) and phosphatidylinositol 3-kinase (LY294002) were used to examine
      the regulation of fibrogenesis. LY294002 but not RAD completely inhibited
      phosphorylation of Akt, while both inhibitors decreased phosphorylation of the S6
      ribosomal protein. RAD and LY decreased foetal calf serum stimulated
      proliferation and DNA synthesis. In addition to their individual effects,
      treatment with both RAD and LY294002 decreased serum-induced fibroblast
      proliferation and DNA synthesis significantly more than either drug alone. TUNEL
      positive cells (apoptosis) in RAD and LY294002 treated groups were not different
      from control groups. In addition to their effect on proliferation, both
      inhibitors also reduced total collagen synthesis. Differentiation studies
      indicated an increase in alpha-smooth muscle actin expression relative to beta
      actin (western blotting), with cytochemistry confirming that all doses of RAD and
      LY294002 increased the proportion of alpha-smooth muscle actin positive cells,
      and hence myofibroblasts. Effects were independent of cell toxicity. These
      results highlight the potential significance of PI3K and mTOR, in the regulation
      of renal (myo)fibroblast activity. The synergistic effects of LY and RAD on
      proliferation suggest that mTOR signalling involves pathways other than
      phosphatidylinositol 3-kinase. These results provide a novel insight into the
      mechanisms of fibroblast regulation during fibrogenesis.

PMID- 16973407
TI  - Dominant lethal effects of 2,4-D in Biomphalaria glabrata.
AB  - Dominant lethal effects of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D)
      were evaluated in the freshwater snail Biomphalaria glabrata. Wild-type snails
      were exposed during 10 days to 50, 75 and 100ppm of 2,4-D dimethylamine salt (2,4
      D DMA) and paired with non-exposed albino snails 1, 11, 25 and 40 days after the
      exposure. The offspring of the non-exposed albino snails was scored for lethal
      malformations. One day after the exposure, a significant effect was observed at
      75 and 100ppm without a dose-response relationship. After 11 days, the effect was
      observed only at the highest dose. After 25 days, significant increases in the
      dominant lethal effects occurred at 50 and 75ppm; effects were directly related
      to the doses. Background levels of lethal malformations were resumed after 40
      days. Although the major and direct measure of dominant lethal mutations is the
      rate of lethal malformations in the heterozygous offspring of the albino snails,
      the sensitivity of the assay was substantially increased with the evaluation of
      all non-viable embryos, that are the sum of those with lethal malformations,
      identified or not as wild-type.

PMID- 16973408
TI  - Protective effect of curcumin on gamma-radiation induced DNA damage and lipid
      peroxidation in cultured human lymphocytes.
AB  - The present work is aimed at evaluating the radioprotective effect of curcumin, a
      naturally occurring phenolic compound on gamma-radiation induced toxicity. The
      cellular changes were estimated by using lipid peroxidative indices like
      thiobarbituric acid reactive substances (TBARS), the antioxidants superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced
      glutathione (GSH). The DNA damage was analysed by using cytokinesis blocked
      micronucleus assay and dicentric aberration (DC). The gamma-radiation at
      different doses (1, 2 and 4Gy) were found to significantly increase micronuclei
      (MN), DC frequencies and TBARS level whereas the levels of GSH and antioxidant
      enzymes were significantly decreased. The maximum damage to lymphocytes was
      observed at 4Gy irradiation. Curcumin pretreatment (1, 5 and 10microg/ml)
      significantly decreased the frequency of MN and DC. The levels of TBARS decreased
      and activities of SOD, CAT and GPx significantly increased along with GSH levels.
      At 1Gy irradiation all the concentrations of curcumin (1, 5 and 10microg/ml)
      significantly protected the lymphocytes from radiation damage. At 2Gy
      irradiation, 5 and 10microg/ml of curcumin showed significant radioprotection.
      Since the highest damage was observed at 4Gy irradiation both 1 and 5microg/ml of
      curcumin pretreatment were not sufficient to protect the lymphocytes from
      radiation damage but 10microg/ml of curcumin significantly protected the cultured
      lymphocytes from radiation damage. Thus, pretreatment with curcumin gives
      protection to lymphocytes against gamma-radiation induced cellular damage.

PMID- 16973410
TI  - Detection of HIV-1 proviral DNA with the AMPLICOR HIV-1 DNA Test, version 1.5,
      following sample processing by the MagNA Pure LC instrument.
AB  - BACKGROUND: The AMPLICOR HIV-1 DNA Test, version 1.5 (AMP HIV-1 DNA 1.5), is a
      new commercially available PCR assay for the detection of human immunodeficiency
      virus type 1 (HIV-1) proviral DNA in human whole blood. OBJECTIVE: This study
      evaluates the performance characteristics of the assay following automated sample
      processing by the MagNA Pure LC instrument (MP). STUDY DESIGN: Analytical
      sensitivity and reproducibility were assessed by testing replicate HIV-1 DNA
      dilution panels over 5 days. Clinical sensitivity and specificity were studied
      among 28 HIV-1 DNA-positive clinical specimens, 60 specimens from healthy blood
      donors, and 63 specimens from HIV-1-seropositive patients with HIV-1 RNA plasma
      levels ranging from <50 to >100,000 copies/mL. RESULTS: Following MP sample
      processing, the assay yielded an analytical sensitivity (95% detection rate) of
      66.3 copies/mL (95% CI, 50.7-106.8), with clinical sensitivity and specificity of
      100%. CONCLUSIONS: MP is a reliable, labor-saving platform capable of processing
      specimens for AMP HIV-1 DNA 1.5. When combined with MP sample processing, AMP HIV
      1 DNA 1.5 is a sensitive and reproducible assay for the detection of HIV-1 DNA in
      clinical whole blood specimens. However, the current AMP HIV-1 DNA 1.5 kit
      configuration may result in inefficient utilization of reagents.

PMID- 16973409
TI  - Quantification of HIV-1 p24 by a highly improved ELISA: an alternative to HIV-1
      RNA based treatment monitoring in patients from Abidjan, Cote d'Ivoire.
AB  - BACKGROUND: Quantification of HIV-1 RNA remains difficult to implement in Africa.
      Simple and inexpensive tests for antiretroviral treatment (ART) monitoring are
      needed. OBJECTIVE: To evaluate an HIV-1 p24 ELISA, which combines efficient virus
      disruption, heat-denaturation and signal amplification, in a West African
      setting. STUDY DESIGN: Eighty-six HIV-1 infected patients from Abidjan, Cote
      d'Ivoire, were tested for p24, HIV-1 RNA, and CD4+ count at baseline, and twice
      within 8 months after ART initiation. RESULTS: All patients responded to ART with
      a minimal HIV-1 RNA drop of 0.5 log(10) at first follow-up. Forty-one (47.7%)
      then rebounded >0.5 log(10) or persisted above 1000 copies/mL by week 24. The
      predicted baseline concentration of p24 corresponding to 100,000 copies/mL of HIV
      1 RNA, above which ART is recommended, was 4546 fg/mL (95% confidence interval
      3148-6566). A prediction model of virologic failure, occurring after an initial
      response to ART, correctly classified 84% of patients using baseline p24, p24
      change on therapy, and achievement of undetectable p24 as explanatory variables.
      The model and further bootstrap evaluation suggested a good ability to
      discriminate between sustained or failing virologic response to ART. CONCLUSION:
      HIV-1 p24 and RNA based-ART monitoring in a low-resource country dominated by HIV
      1 CRF02 AG appeared comparable.

PMID- 16973411
TI  - Simplified PCR protocols for INNO-LiPA HBV Genotyping and INNO-LiPA HBV PreCore
      assays.
AB  - BACKGROUND: INNO-LiPA HBV Genotyping (LiPA HBV GT) and INNO-LiPA HBV PreCore
      (LiPA HBV PC) are commercially available assays for hepatitis B virus (HBV)
      characterization. These assays are labor-intensive and may be prone to exogenous
      DNA contamination due to their use of nested PCR amplification procedures and
      lack of contamination control measures. OBJECTIVE: Standardized, single-round
      INNO-LiPA PCR amplification protocols incorporating uracil N-glycosylase and
      automated sample processing by the MagNA Pure LC instrument were evaluated. STUDY
      DESIGN: HBV standards containing 10,000, 1000, 100, 10, and 0 IU/mL were analyzed
      to determine the analytical sensitivity and reproducibility of these modified
      procedures. One hundred clinical serum specimens with viral titers ranging from
      390 to 16,900,000 IU/mL were tested by modified LiPA HBV GT, while 34 specimens
      with viral titers ranging from 378 to 11,600,000 IU/mL were tested by modified
      LiPA HBV PC. RESULTS: Modified LiPA HBV GT and LiPA HBV PC each yielded
      analytical sensitivities of 100% at an HBV DNA level of 1000 IU/mL and 90% at a
      level of 100 IU/mL. Among clinical specimens, success rates for both INNO-LiPA
      procedures were > or =94%. CONCLUSIONS: Both modified INNO-LiPA procedures were
      sensitive and reproducible, with improved efficiency and suitability for routine
      laboratory use.

PMID- 16973412
TI  - Rapid detection of Epstein-Barr virus DNA by loop-mediated isothermal
      amplification method.
AB  - BACKGROUND: The loop-mediated isothermal amplification (LAMP) method is a novel
      technique for the amplification of specific DNA sequences. OBJECTIVES: To
      establish the LAMP method for amplifying Epstein-Barr virus (EBV) DNA and to
      examine its reliability for the detection of EBV DNA in clinical specimens. STUDY
      DESIGN: Sera from 108 patients, who were initially suspected of primary EBV
      infection, were tested by the EBV LAMP method, and the results were compared with
      those of the real-time PCR assay. Serological examination was regarded as the
      standard diagnostic method. RESULTS: To diagnose primary EBV infection, the
      sensitivity of LAMP was 86.4% and the specificity was 100%. The sensitivity of
      the real-time PCR assay was 84.1% and the specificity was 98.4%. Longitudinal
      analysis showed that the detection rate of EBV DNA in serum by the LAMP method
      decreased with time in accordance with the decrease of the EBV load. EBV DNA
      could not be detected in serum 40 days after onset of symptoms. CONCLUSIONS:
      These results indicate that the sensitivity and specificity of the LAMP method
      are comparable to those of real-time PCR and that detecting EBV DNA in serum by
      this method is potentially useful for diagnosing primary EBV infection.

PMID- 16973413
TI  - The phospholipase A2 superfamily and its group numbering system.
AB  - The superfamily of phospholipase A(2) (PLA(2)) enzymes currently consists of 15
      Groups and many subgroups and includes five distinct types of enzymes, namely the
      secreted PLA(2)s (sPLA(2)), the cytosolic PLA(2)s (cPLA(2)), the Ca(2+)
      independent PLA(2)s (iPLA(2)), the platelet-activating factor acetylhydrolases
      (PAF-AH), and the lysosomal PLA(2)s. In 1994, we established the systematic Group
      numbering system for these enzymes. Since then, the PLA(2) superfamily has grown
      continuously and over the intervening years has required several updates of this
      Group numbering system. Since our last update, a number of new PLA(2)s have been
      discovered and are now included. Additionally, tools for the investigation of
      PLA(2)s and approaches for distinguishing between the different Groups are
      described.

PMID- 16973414
TI  - Death of the "ologies".

PMID- 16973415
TI  - Measures to improve knowledge and self-care among patients with COPD: A UK
      general practice audit.
AB  - The Parchmore Partnership, London, audited 11 evidence-based criteria relating to
      patient knowledge and COPD morbidity during December 2004 to March 2005 using
      questionnaires and practice records. 32 patients with moderate to severe COPD
      participated, and during the project they received information and extra care.
      Patient knowledge and clinical indicators showed significant improvements.

PMID- 16973416
TI  - Montelukast is an effective monotherapy for mild asthma and for asthma with co
      morbid allergic rhinitis.

PMID- 16973417
TI  - Are six seconds long enough?

PMID- 16973418
TI  - PPARalpha and PPARgamma dual agonists for the treatment of type 2 diabetes and
      the metabolic syndrome.
AB  - The discovery of the crucial role of peroxisome proliferator-activated receptors
      (PPARs) as regulators of lipid and glucose metabolism has raised interest in the
      development of synthetic ligands as potential tools for therapeutic intervention
      in type 2 diabetes and the metabolic syndrome. PPARalpha activators primarily
      improve dyslipidemia, whereas thiazolidinediones are potent PPARgamma activators
      that improve insulin resistance. Important research programs to develop agonists
      that combine the therapeutic effects of both PPARalpha- and PPARgamma-selective
      agonists, creating the expectation of greater efficacy and other advantages in
      the treatment of type 2 diabetes and the metabolic syndrome, have therefore been
      undertaken. Among these dual PPARalpha/gamma agonists, compounds that belong to
      the glitazar class are in the most advanced stage of development. However,
      although they demonstrated beneficial impact over selective PPAR agonists by
      improving both lipid and glucose homeostasis, safety has been a critical issue
      and has led to the discontinuation of their development because of adverse
      toxicity profiles. However, the target-related mechanism responsible for the
      identified safety issues and the relevance of rodent toxicities to the human
      situation are unclear. Therefore, future development of dual PPARalpha/gamma
      agonists with selective PPAR modulator activity appears appropriate and should be
      feasible.

PMID- 16973419
TI  - Serotonergic receptors in therapeutic approaches to gastrointestinal disorders.
AB  - Most of the cloned serotonin (5-HT) receptor subtypes are present on enteric
      neurons that control gastrointestinal function. Because of the wide distribution
      of 5-HT receptor subtypes in the gut, the precise actions of currently marketed
      drugs are unclear. Furthermore, efficacy of these drugs varies between
      individuals. Two recent advances provide important potential explanations for
      this phenomenon: polymorphisms have recently been discovered in the gene for the
      key enzyme in neural 5-HT production, and physiologically relevant 5-HT(4)
      receptor splice variants have been shown to be differentially located across
      intestinal regions. Functional 5-HT(7) receptors have recently been demonstrated
      in the gut and, together with the 5-HT(1A) receptor, offer new therapeutic
      options. In addition, recently suggested identities for the elusive 5-HT(1P)
      receptor could result in other, more effective therapeutic targets.

PMID- 16973420
TI  - Role of adipokines in the control of energy metabolism: focus on adiponectin.
AB  - Leptin and adiponectin are the major adipokines secreted by fat cells. Leptin
      effects energy homeostasis by decreasing food intake and by acting on lipogenesis
      and fatty acid oxidation. Elucidation of the mechanisms of action of adiponectin
      (Acrp30), a hormone considered to be a major insulin-sensitizing hormone, and
      leptin has been improved by the delineation of their impact on muscle and liver
      cells via regulation of AMP kinase function. A recent study has defined a human
      skeletal muscle pathway by which adiponectin increases mitochondrial number and
      function. In addition, adiponectin signaling pathways have recently been
      clarified by the discovery of a protein that interacts with adiponectin
      receptors.

PMID- 16973421
TI  - The American cotton rat: a novel model for pulmonary tuberculosis.
AB  - Several animal models are used to study Mycobacterium tuberculosis (MTB)
      infections, but none is a fully ideal model of human disease. The American cotton
      rat is an excellent model for the study of several human viral and bacterial
      respiratory infectious diseases, but until now has not been reported to be a
      model with MTB infection. Preliminary experiments were designed in which two
      species of cotton rats (Sigmodon hispidus and Sigmodon fulviventer) received
      respiratory challenges with M. tuberculosis via either intranasal or aerosol
      inoculation. Granulomatous disease, often with central necrosis, developed in the
      lungs, spleen, and lymph nodes of infected animals. The number of MTB bacilli in
      the lungs increased logarithmically until reaching a plateau in the second month
      after aerosol inoculation. There were differences in response to infection
      between the two species, with S. fulviventer demonstrating greater mortality than
      S. hispidus. Cytokine gene expression analysis by reverse transcriptase
      polymerase chain reaction (RT-PCR) was performed on both normal appearing and
      granulomatous lung tissue from infected animals. Many cytokine genes were more
      highly expressed in the focal areas of inflammation. Cotton rats provide another
      valuable tool in future research with tuberculosis.

PMID- 16973422
TI  - Anguish over angiopathy: hemolytic uremic syndrome.

PMID- 16973423
TI  - Use of continuous subcutaneous insulin infusion in patients with cystic fibrosis
      related diabetes: three case reports.
AB  - We used insulin pump therapy in three patients (two males and one female; age
      5.5, 21 and 28.2 years, respectively) with CFRD and we reported the experience of
      2 years of follow-up. In all the patients during the CSII treatment, the annual
      mean level of HbA1c reduced and the annual mean level of BMI increased,
      respected, the year before starting the CSII (in MDI treatment with 4
      injections/day). The insulin requirements decreased during the CSII treatment and
      respected MDI treatment. During the CSII treatment, none of the patients
      exhibited episodes of DKA or severe hypoglycaemia. Only two episodes of
      lipohypertrophy and a slight local cutaneous inflammation were reported.
      CONCLUSIONS: The use of CSII in our patients with CFRD improves the metabolic
      control of diabetes and the nutritional status with no concomitant problems
      related to this treatment.

PMID- 16973424
TI  - Influence of epithelium on beta-adrenoceptor desensitization of guinea pig
      tracheal smooth muscle.
AB  - The effect of tissue incubation with a beta2-agonist of denuded and intact
      epithelium trachea on the responsiveness to isoprenaline and beta-receptor
      blocked by propranolol (CR-1) was examined in this study. We examined the effect
      of epithelium removal on the beta-adrenoceptor desensitization resulting from
      incubation of guinea pig trachea in the beta-adrenergic agonist isoprenaline (10
      microM). Desensitization was measured as the change in EC50, the concentration of
      beta-agonist that produced 50% relaxation of tracheal rings contracted with
      methacholine. As a second measure of desensitization, we measured the shift in
      EC50 resulting from incubation of tracheal rings with the beta-adrenoceptor
      antagonist propranolol (20 nM), expressed as CR-1 ([post-propranolol
      EC50/baseline EC50]-1). Initially, we measured desensitization immediately after
      incubation in isoprenaline; subsequently, we repeated the protocol and allowed a
      30 min rest between the end of incubation and the measurement. The sensitivity of
      denuded epithelium trachea to isoprenaline and (CR-1) was significantly higher
      than that of intact epithelium only in non-incubated preparations (p<0.05 to
      p<0.001). Incubation to isoprenaline caused a significant reduction in the
      tracheal response to isoprenaline in both the denuded groups (p<0.005 for both
      cases) and intact epithelium groups (p<0.05 for both cases). Incubation to
      isoprenaline also caused a significant reduction in (CR-1) value in both the
      denuded groups (p<0.005 for group 2 and p<0.001 for group 4) and intact
      epithelium only in group 1 (p<0.05). However, the changes in EC50 due to tissue
      incubation with isoprenaline were significantly greater in denuded than intact
      epithelium trachea (p<0.05 for all cases) and for CR-1 value only in groups 1 and
      2 (p<0.05). These results indicate decrease in both tracheal response to beta
      agonist (tolerance) and CR-1 (due to incubation of tissues with isoprenaline),
      which were greater in denuded epithelium groups.

PMID- 16973425
TI  - Gel electrophoresis of polyphenol oxidase with instant identification by in situ
      blotting.
AB  - Polyphenol oxidase (PPO) or tyrosinase is an important and ubiquitous enzyme
      responsible for browning in plants and melanization in animals. The molecular
      size of the plant PPO is varied among the species and its activity can be
      enhanced by a variety of anionic detergents. In the present study, we developed a
      simple method for the first-step identification of PPO in fruit and vegetable
      extracts. First, 3mm chromatographic paper was immersed in 0.5% (w/v) catechol
      solution as an immobilized PPO substrate. After running the extract with 10%
      sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), one side
      of the glass plate was removed. The plate was immediately laid on top of the
      dried catechol-paper. A dark-brown band corresponding to PPO was visualized
      within 1 min and was further confirmed by a conventional Western blot using an
      antibody prepared against mushroom PPO. It also reveals that some vegetation
      (such as tomato, radish, and oriental melon) with low or no detectable activity
      in a conventional enzyme assay actually possessed marked levels of PPO activity
      when assessed by PAGE-blot. We propose that an inhibitor is associated with PPO
      in some plants; the inhibitor, however, is dissociated during the
      electrophoresis. Therefore, in addition to identify the molecular form of PPO,
      the present technique may explore the existence of PPO inhibitor(s) in plants.
      The detail of the method with respect to its relevance for searching a natural
      PPO inhibitor is described and discussed.

PMID- 16973426
TI  - An Australian history of the subordination of midwifery.
AB  - This paper analyses the history of the subordination of midwifery to medicine and
      nursing. With the important exception of Evan Willis' work on medical dominance
      and Annette Summers' work on the takeover of midwifery by nursing, other
      histories of Australian midwifery have taken a neutral approach to issue of power
      and control. The aim of analysing this period is to identify the strategies of
      power that were used to subordinate midwifery. With increased consciousness of
      how power has operated in the past, midwives and woman of today can be more
      empowered when seeking to promote normal birth and midwifery models of care.
      Concepts of 'power', 'the state' and midwife are defined and discussed. A summary
      of the decline of midwifery and the rise of obstetrics in Europe and the United
      Kingdom (UK) gives a background against which to understand the Australian
      experience. The historical account given here draws to a climax by focussing on
      the period 1886-1928. It was during this time that medicine forged an alliance
      with nursing and achieved both legal and disciplinary control of midwifery.
      Knowing how this was done is important because it helps us to recognise the power
      strategies that are currently being used by medicine. This is helpful when
      planning how these strategies might be matched or countered by contemporary woman
      and midwives when seeking to promote normal birth and midwifery models of care.

PMID- 16973427
TI  - Osteoinductivity of demineralized bone matrix in immunocompromised mice and rats
      is decreased by ovariectomy and restored by estrogen replacement.
AB  - The osteoinduction potential of human demineralized bone matrix (DBM) in females
      with low estrogen (E2) is unknown. Moreover, the osteoinductivity of commercial
      human DBM is tested in male athymic rats and mice, but DBM performance in these
      animals may not reflect performance in female animals or provide information on
      E2's role in the process. To gain insight, human DBM was implanted bilaterally in
      the gastrocnemius of twenty-four athymic female mice (10 mg/implant) and twenty
      four athymic female rats (15 mg/implant). Eight animals in each group were sham
      operated (SHAM), ovariectomized (OVX), or ovariectomized with E2-replacement
      (OVX+E2) via subcutaneous slow release capsules of 17beta-estradiol. OVX and
      OVX+E2 animals were pair-fed to SHAM animals. Four animals from each group were
      euthanized at 35 days and four at 56 days. Animal weight, uterine weight, and
      blood estrogen levels confirmed that pair feeding, ovariectomy, and E2
      replacement were successful. Histological sections of implanted tissues were
      evaluated qualitatively for absence or presence of DBM, ossicle formation, and
      new bone or cartilage using a previously developed qualitative scoring system
      (QS) and by histomorphometry to obtain a quantitative assessment of
      osteoinduction. OVX mice had a small but significant QS decrease at 35 days
      compared to SHAM mice, confirmed by quantitative measurement of ossicle, marrow
      space, and new bone areas. The QS in rats was not affected by OVX but
      histomorphometry showed decreased new bone in OVX rats, which was restored by E2.
      The QS indicated that the number of new bone sites was not reduced by OVX in rats
      or mice at 56 days, but the relative amount of new bone v. marrow space was
      affected and differed with animal species. Residual DBM was less in OVX animals,
      indicating that DBM resorption was affected. Cartilage was present in rats but
      not in mice, suggesting that endochondral ossification was slower and indicating
      that bone graft studies in these species are not necessarily comparable. These
      results show the importance of E2 in human DBM-induced bone formation and suggest
      that E2 may be needed for clinical effectiveness in post-menopausal women.

PMID- 16973428
TI  - Cotranslocational degradation: utilitarianism in the ER stress response.
AB  - Recently, a new layer of the unfolded protein response was discovered that
      supports the cotranslocational degradation of nascent chains stalled in
      endoplasmic reticulum translocons (Oyadomari et al., 2006).

PMID- 16973429
TI  - SnoRNP biogenesis meets Pre-mRNA splicing.
AB  - In vertebrates, hundreds of small nucleolar RNAs (snoRNAs) are processed from pre
      mRNA introns. In the September 1 issue of Molecular Cell, Hirose et al. (2006)
      demonstrate that a spliceosomal intron binding protein, IBP160, couples box C/D
      snoRNA processing with pre-mRNA splicing in the C1 splicing complex.

PMID- 16973430
TI  - HATs off to PIC assembly.
AB  - There are many regulated steps in the assembly of a transcription preinitiation
      complex (PIC). In this issue of Molecular Cell, Black et. al. (2006) reveal a
      catalytic switch mechanism in which autoacetylation of the HAT p300 triggers its
      dissociation from a promoter in a manner that is coupled to TFIID association.

PMID- 16973431
TI  - A recurrent phospho-sumoyl switch in transcriptional repression and beyond.
AB  - How multisite posttranslational modification coordinates dynamic regulation of
      protein function is an issue fundamental to many biological processes. Related to
      this, a composite sequence motif has recently been identified that couples
      phosphorylation, sumoylation, and perhaps also deacetylation to control
      transcriptional repression in stress response, mitogen and nuclear hormone
      signaling, myogenesis, and neuronal differentiation. This motif is present in
      many proteins, integrates cellular signals from diverse pathways, and serves as a
      valuable signature for in silico identification of proteins regulated by adjacent
      phosphorylation and sumoylation.

PMID- 16973432
TI  - The DNA repair helicases XPD and FancJ have essential iron-sulfur domains.
AB  - DNA helicases are essential components of the cellular machinery for DNA
      replication, recombination, repair, and transcription. The XPD and FancJ proteins
      are related helicases involved in the nucleotide excision repair (NER) and
      Fanconi anemia repair pathways, respectively. We demonstrate that both proteins
      have a conserved domain near the N terminus that includes an iron-sulfur (Fe-S)
      cluster. Three absolutely conserved cysteine residues provide ligands for the Fe
      S cluster, which is essential for the helicase activity of XPD. Yeast strains
      harboring mutations in the Fe-S domain of Rad3 (yeast XPD) are defective in
      excision repair of UV photoproducts. Clinically relevant mutations in patients
      with trichothiodystrophy (TTD) and Fanconi anemia disrupt the Fe-S clusters of
      XPD and FancJ and thereby abolish helicase activity.

PMID- 16973433
TI  - A mechanism for coordinating chromatin modification and preinitiation complex
      assembly.
AB  - Transcription of eukaryotic genes within a chromatin environment requires the
      sequential recruitment of histone modification enzymes and the general
      transcription factors (GTFs) by activators. However, it is unknown how
      preinitiation complex assembly is coordinated with chromatin modification. Here,
      we show that the model activator GAL4-VP16 directs the ordered assembly of
      Mediator, histone acetyltransferases (HATs), and GTFs onto immobilized chromatin
      and naked DNA templates in vitro. Using purified proteins, we found that the
      Mediator regulates this assembly process by binding to p300 and TFIID. An acetyl
      CoA-dependent catalytic switch causes p300 to acetylate chromatin and then
      dissociate. Dissociation of p300 enhances TFIID binding and active transcription.
      The dissociation is caused by an autoacetylation-induced conformational change in
      the catalytic domain of p300. We conclude that autoacetylation-induced
      dissociation of p300 acts as a catalytic switch, which allows TFIID binding and
      subsequent preinitiation complex assembly.

PMID- 16973434
TI  - PP1/PP2A phosphatases are required for the second step of Pre-mRNA splicing and
      target specific snRNP proteins.
AB  - Pre-mRNA splicing is a complex and dynamic process in which protein
      phosphorylation and dephosphorylation both play important roles. Although
      specific phosphatases, such as PP1 and PP2A, have been implicated in splicing,
      direct evidence for their involvement has been lacking, and their exact
      function(s) in this process remain unknown. In this study, we show that PP1 and
      certain PP2A family phosphatases play essential but redundant roles in splicing.
      Unexpectedly, we found that these phosphatases are required principally for the
      second step of the splicing reaction. Furthermore, we provide evidence that
      components of U2 and U5 snRNPs, specifically SAP155 and U5-116 kDa, are the key
      spliceosomal substrates for these phosphatases. Based on these data, we propose
      that dephosphorylation of U2 and U5 snRNP components by PP1/PP2A family
      phosphatases facilitates essential structural rearrangements in the spliceosome
      during the transition from the first to the second step.

PMID- 16973435
TI  - The receptor for branch-site docking within a group II intron active site.
AB  - The distinguishing feature of group II introns, and the property that links them
      with spliceosomal catalysis, is their ability to undergo splicing through
      branching. In this reaction, the 2'-hydroxyl group of a specific adenosine within
      intron domain 6 serves as the nucleophile for attack on the 5' splice site. We
      know less about branching than any other feature of group II intron catalysis,
      largely because the receptor structure for activating the branch site is unknown.
      Here, we identify the intronic region that binds the branch site of a group IIB
      intron. Located in domain 1, close to receptors for intron domain 5 and both
      splice sites, we demonstrate that the branch-site receptor is a functional
      element required for transesterification. Furthermore, we show that crosslinked
      branch sites can carry out both steps of splicing, suggesting that the
      conformational state of the intron core is set early and that it persists
      throughout the entire splicing process.

PMID- 16973436
TI  - Termination of cryptic unstable transcripts is directed by yeast RNA-binding
      proteins Nrd1 and Nab3.
AB  - Studies of yeast transcription have revealed the widespread distribution of
      intergenic RNA polymerase II transcripts. These cryptic unstable transcripts
      (CUTs) are rapidly degraded by the nuclear exosome. Yeast RNA binding proteins
      Nrd1 and Nab3 direct termination of sn/snoRNAs and recently have also been
      implicated in premature transcription termination of the NRD1 gene. In this
      paper, we show that Nrd1 and Nab3 are required for transcription termination of
      CUTs. In nrd1 and nab3 mutants, we observe 3'-extended transcripts originating
      from CUT promoters but failing to terminate through the Nrd1- and Nab3-directed
      pathway. Nrd1 and Nab3 colocalize to regions of the genome expressing antisense
      CUTs, and these transcripts require yeast nuclear exosome and TRAMP components
      for degradation. Dissection of a CUT terminator reveals a minimal element
      sufficient for Nrd1- and Nab3-directed termination. These results suggest that
      transcription termination of CUTs directed by Nrd1 and Nab3 is a prerequisite for
      rapid degradation by the nuclear exosome.

PMID- 16973437
TI  - Transcription termination and nuclear degradation of cryptic unstable
      transcripts: a role for the nrd1-nab3 pathway in genome surveillance.
AB  - Cryptic unstable transcripts (CUTs) are widely distributed in the genome of S.
      cerevisiae. These RNAs generally derive from nonannotated regions of the genome
      and are degraded rapidly and efficiently by the nuclear exosome via a pathway
      that involves degradative polyadenylation by a new poly(A) polymerase borne by
      the TRAMP complex. What is the share of significant information that is encrypted
      in CUTs and what distinguishes a CUT from other Pol II transcripts are unclear to
      date. Here we report the dissection of the molecular mechanism that leads to
      degradation of a model CUT, NEL025c. We show that the Nrd1p-Nab3p-dependent
      pathway, involved in transcription termination of sno/snRNAs, is required, albeit
      not sufficient, for efficient degradation of NEL025c RNAs and at least a subset
      of other CUTs. Our results suggest an important role for the Nrd1p-Nab3p pathway
      in the control of gene expression throughout the genome.

PMID- 16973438
TI  - Deletion of a conserved, central ribosomal intersubunit RNA bridge.
AB  - Elucidation of the structure of the ribosome has stimulated numerous proposals
      for the roles of specific rRNA elements, including the universally conserved
      helix 69 (H69) of 23S rRNA, which forms intersubunit bridge B2a and contacts the
      D stems of A- and P-site tRNAs. H69 has been proposed to be involved not only in
      subunit association and tRNA binding but also in initiation, translocation,
      translational accuracy, the peptidyl transferase reaction, and ribosome
      recycling. Consistent with such proposals, deletion of H69 confers a dominant
      lethal phenotype. Remarkably, in vitro assays show that affinity-purified
      Deltah69 ribosomes have normal translational accuracy, synthesize a full-length
      protein from a natural mRNA template, and support EF-G-dependent translocation at
      wild-type rates. However, Deltah69 50S subunits are unable to associate with 30S
      subunits in the absence of tRNA, are defective in RF1-catalyzed peptide release,
      and can be recycled in the absence of RRF.

PMID- 16973439
TI  - An arsenite-inducible 19S regulatory particle-associated protein adapts
      proteasomes to proteotoxicity.
AB  - Protein misfolding caused by exposure to arsenite is associated with
      transcriptional activation of the AIRAP gene. We report here that AIRAP is an
      arsenite-inducible subunit of the proteasome's 19S cap that binds near PSMD2 at
      the 19S base. Compared to the wild-type, knockout mouse cells or C. elegans
      lacking AIRAP accumulate more polyubiquitylated proteins and exhibit higher
      levels of stress when exposed to arsenite, and proteasomes isolated from arsenite
      treated AIRAP knockout cells are relatively impaired in substrate degradation in
      vitro. AIRAP's association with the 19S cap reverses the stabilizing affect of
      ATP on the 26S proteasome during particle purification, and AIRAP-containing
      proteasomes, though constituted of 19S and 20S subunits, acquire features of
      hybrid proteasomes with both 19S and 11S regulatory caps. These features include
      enhanced cleavage of peptide substrates and suggest that AIRAP adapts the cell's
      core protein degradation machinery to counteract proteotoxicity induced by an
      environmental toxin.

PMID- 16973440
TI  - Chaperonin TRiC promotes the assembly of polyQ expansion proteins into nontoxic
      oligomers.
AB  - Aberrant folding and fibrillar aggregation by polyglutamine (polyQ) expansion
      proteins are associated with cytotoxicity in Huntington's disease and other
      neurodegenerative disorders. Hsp70 chaperones have an inhibitory effect on fibril
      formation and can alleviate polyQ cytotoxicity. Here we show that the cytosolic
      chaperonin, TRiC, functions synergistically with Hsp70 in this process and is
      limiting in suppressing polyQ toxicity in a yeast model. In vitro reconstitution
      experiments revealed that TRiC, in cooperation with the Hsp70 system, promotes
      the assembly of polyQ-expanded fragments of huntingtin (Htt) into soluble
      oligomers of approximately 500 kDa. Similar oligomers were observed in yeast
      cells upon TRiC overexpression and were found to be benign, in contrast to
      conformationally distinct Htt oligomers of approximately 200 kDa, which
      accumulated at normal TRiC levels and correlated with inhibition of cell growth.
      We suggest that TRiC cooperates with the Hsp70 system as a key component in the
      cellular defense against amyloid-like protein misfolding.

PMID- 16973441
TI  - JNK2 is a positive regulator of the cJun transcription factor.
AB  - The cJun NH(2)-terminal kinase (JNK) signal transduction pathway is established
      to be an important mechanism of regulation of the cJun transcription factor.
      Studies of Jnk1(-/-) and Jnk2(-/-) mice suggest that the JNK1 and JNK2 isoforms
      have opposite effects on cJun expression and proliferation. Here, we demonstrate,
      using a chemical genetic approach, that both JNK1 and JNK2 are positive
      regulators of these processes. We show that competition between JNK1 and JNK2
      contributes to the opposite phenotypes caused by JNK1 and JNK2 deficiency. Our
      analysis illustrates the power of a chemical genetics approach for the analysis
      of signal transduction pathways and also highlights the limitations of single
      gene knockout strategies for the analysis of signaling pathways that are formed
      by a network of interacting proteins.

PMID- 16973442
TI  - Large conformational changes in a kinesin motor catalyzed by interaction with
      microtubules.
AB  - Kinesin motor proteins release nucleotide upon interaction with microtubules
      (MTs), then bind and hydrolyze ATP to move along the MT. Although crystal
      structures of kinesin motors bound to nucleotides have been solved, nucleotide
      free structures have not. Here, using cryomicroscopy and three-dimensional (3D)
      reconstruction, we report the structure of MTs decorated with a Kinesin-14 motor,
      Kar3, in the nucleotide-free state, as well as with ADP and AMPPNP, with
      resolution sufficient to show alpha helices. We find large structural changes in
      the empty motor, including melting of the switch II helix alpha4, closure of the
      nucleotide binding pocket, and changes in the central beta sheet reminiscent of
      those reported for nucleotide-free myosin crystal structures. We propose that the
      switch II region of the motor controls docking of the Kar3 neck by conformational
      changes in the central beta sheet, similar to myosin, rather than by rotation of
      the motor domain, as proposed for the Kif1A kinesin motor.

PMID- 16973443
TI  - Dynamic regulation of cAMP synthesis through anchored PKA-adenylyl cyclase V/VI
      complexes.
AB  - Spatiotemporal organization of cAMP signaling begins with the tight control of
      second messenger synthesis. In response to agonist stimulation of G protein
      coupled receptors, membrane-associated adenylyl cyclases (ACs) generate cAMP that
      diffuses throughout the cell. The availability of cAMP activates various
      intracellular effectors, including protein kinase A (PKA). Specificity in PKA
      action is achieved by the localization of the enzyme near its substrates through
      association with A-kinase anchoring proteins (AKAPs). Here, we provide evidence
      for interactions between AKAP79/150 and ACV and ACVI. PKA anchoring facilitates
      the preferential phosphorylation of AC to inhibit cAMP synthesis. Real-time
      cellular imaging experiments show that PKA anchoring with the cAMP synthesis
      machinery ensures rapid termination of cAMP signaling upon activation of the
      kinase. This protein configuration permits the formation of a negative feedback
      loop that temporally regulates cAMP production.

PMID- 16973444
TI  - Acrylamide: review of toxicity data and dose-response analyses for cancer and
      noncancer effects.
AB  - Acrylamide (ACR) is used in the manufacture of polyacrylamides and has recently
      been shown to form when foods, typically containing certain nutrients, are cooked
      at normal cooking temperatures (e.g., frying, grilling or baking). The toxicity
      of ACR has been extensively investigated. The major findings of these studies
      indicate that ACR is neurotoxic in animals and humans, and it has been shown to
      be a reproductive toxicant in animal models and a rodent carcinogen. Several
      reviews of ACR toxicity have been conducted and ACR has been categorized as to
      its potential to be a human carcinogen in these reviews. Allowable levels based
      on the toxicity data concurrently available had been developed by the U.S. EPA.
      New data have been published since the U.S. EPA review in 1991. The purpose of
      this investigation was to review the toxicity data, identify any new relevant
      data, and select those data to be used in dose-response modeling. Proposed
      revised cancer and noncancer toxicity values were estimated using the newest U.S.
      EPA guidelines for cancer risk assessment and noncancer hazard assessment.
      Assessment of noncancer endpoints using benchmark models resulted in a reference
      dose (RfD) of 0.83 microg/kg/day based on reproductive effects, and 1.2
      microg/kg/day based on neurotoxicity. Thyroid tumors in male and female rats were
      the only endpoint relevant to human health and were selected to estimate the
      point of departure (POD) using the multistage model. Because the mode of action
      of acrylamide in thyroid tumor formation is not known with certainty, both linear
      and nonlinear low-dose extrapolations were conducted under the assumption that
      glycidamide or ACR, respectively, were the active agent. Under the U.S. EPA
      guidelines (2005), when a chemical produces rodent tumors by a nonlinear or
      threshold mode of action, an RfD is calculated using the most relevant POD and
      application of uncertainty factors. The RfD was estimated to be 1.5 microg/kg/day
      based on the use of the area under the curve (AUC) for ACR hemoglobin adducts
      under the assumption that the parent, ACR, is the proximate carcinogen in rodents
      by a nonlinear mode of action. When the mode of action in assumed to be linear in
      the low-dose region, a risk-specific dose corresponding to a specified level of
      risk (e.g., 1 x 10-5) is estimated, and, in the case of ACR, was 9.5 x 10-2
      microg ACR/kg/day based on the use of the AUC for glycidamide adduct data.
      However, it should be noted that although this review was intended to be
      comprehensive, it is not exhaustive, as new data are being published
      continuously.

PMID- 16973445
TI  - The toxicology of mercury and its chemical compounds.
AB  - This review covers the toxicology of mercury and its compounds. Special attention
      is paid to those forms of mercury of current public health concern. Human
      exposure to the vapor of metallic mercury dates back to antiquity but continues
      today in occupational settings and from dental amalgam. Health risks from
      methylmercury in edible tissues of fish have been the subject of several large
      epidemiological investigations and continue to be the subject of intense debate.
      Ethylmercury in the form of a preservative, thimerosal, added to certain
      vaccines, is the most recent form of mercury that has become a public health
      concern. The review leads to general discussion of evolutionary aspects of
      mercury, protective and toxic mechanisms, and ends on a note that mercury is
      still an "element of mystery."

PMID- 16973446
TI  - A model for communication skills assessment across the undergraduate curriculum.
AB  - Physicians' interpersonal and communication skills have a significant impact on
      patient care and correlate with improved healthcare outcomes. Some studies
      suggest, however, that communication skills decline during the four years of
      medical school. Regulatory and other medical organizations, recognizing the
      importance of interpersonal and communication skills in the practice of medicine,
      now require competence in communication skills. Two challenges exist: to select a
      framework of interpersonal and communication skills to teach across undergraduate
      medical education, and to develop and implement a uniform model for the
      assessment of these skills. The authors describe a process and model for
      developing and institutionalizing the assessment of communication skills across
      the undergraduate curriculum. Consensus was built regarding communication skill
      competencies by working with course leaders and examination directors, a uniform
      framework of competencies was selected to both teach and assess communication
      skills, and the framework was implemented across the Harvard Medical School
      undergraduate curriculum. The authors adapted an assessment framework based on
      the Bayer-Fetzer Kalamazoo Consensus Statement adapted a patient and added and
      satisfaction tool to bring patients' perspectives into the assessment of the
      learners. The core communication competencies and evaluation instruments were
      implemented in school-wide courses and assessment exercises including the first
      year Patient-Doctor I Clinical Assessment, second-year Objective Structured
      Clinical Exam (OSCE), third-year Patient-Doctor III Clinical Assessment, fourth
      year Comprehensive Clinical Practice Examination and the Core Medicine
      Clerkships. Faculty were offered workshops and interactive web-based teaching to
      become familiar with the framework, and students used the framework with repeated
      opportunities for faculty feedback on these skills. A model is offered for
      educational leaders and others who are involved in designing assessment in
      communication skills. By presenting an approach for implementation, the authors
      hope to provide guidance for the successful integration of communication skills
      assessment in undergraduate medical education.

PMID- 16973447
TI  - Improving medical student performance in smoking health promotion: effect of a
      vertically integrated curriculum.
AB  - The majority of medical schools have curricula that address the health effects of
      smoking. However, there are many gaps in smoking education, especially in
      relationship to vertical integration. The authors aimed to determine whether
      medical students would better address adolescent smoking within a vertically
      integrated curriculum in comparison with the previous traditional curriculum.
      They studied two groups of fifth-year students; one group received a specific
      smoking intervention. Each group consisted of the entire cohort of students
      within the Child and Adolescent Health rotation of a newly designed medical
      curriculum. Two groups of students from the previous traditional undergraduate
      curriculum were available for direct comparison, one of which had received the
      same teaching on adolescent smoking. An objective structured clinical examination
      station was used to measure adolescent smoking enquiry. Intervention students in
      the new curriculum were more likely to enquire about smoking in the objective
      structured clinical examination than students who did not receive the
      intervention (p < 0.005). New curriculum students performed better than students
      from the previous curriculum, whether or not they had received the smoking
      intervention (p < 0.001). This study suggests that integrated undergraduate
      teaching can improve student clinical behaviours with regard to opportunistic
      smoking enquiry in adolescents.

PMID- 16973448
TI  - 'Losing my touch': decline in self-reported confidence in performing practical
      procedures in consultant oncologists.
AB  - This study aimed to compare the confidence of oncology consultants and specialist
      registrars (SpRs) in the performance of practical procedures, to contrast this
      with confidence in other areas of practice and to determine at what grade they
      felt most confident. Questionnaires were sent to all 57 oncology consultants and
      SpRs in the South-West region. Respondents scored confidence on a five-point
      Likert scale. The response rate was 70%. SpRs were significantly more confident
      in cardiopulmonary resuscitation (p = 0.003) and central line insertion (p =
      0.006). Consultants were significantly more confident in developing management
      plans (p = 0.001) and performing committee work (p = 0.002). Only 6% of
      consultants felt most confident performing practical procedures as a consultant,
      and were less confident about these than other tasks (p = 0.001). Some 86% of
      SpRs considered they were more confident performing practical procedures as
      senior house officers (SHOs). In conclusion, self-reported confidence in
      performing practical procedures declines during career progression in oncology.
      This raises questions about the teaching and supervision of these procedures. If
      there is a greater emphasis on a consultant-provided service, their educational
      needs will need to be recognized and retraining or outsourcing of these
      procedures to other specialties may be necessary.

PMID- 16973449
TI  - Student diversity at Erasmus Medical Centre Rotterdam: does it make any
      difference?
AB  - In an ethnically diverse society cultural competence is indispensable for medical
      doctors. At present 10% of the Dutch population are first- or second-generation
      non-Western immigrants. With 8% Western and 18% non-Western immigrants,
      originating from 30 different countries, the 2001 Rotterdam first-year students
      highly out-rated the national average of immigrant medical students. Diverse
      student populations may enhance students' cultural competence but can also
      generate conflicts or even racism. This was the first Dutch study on expectations
      and experiences of medical students related to their ethnic and religious
      background. In December 2001 all first-year students were approached with an
      anonymous questionnaire, including statements on the expected influence of their
      culture and religion on their medical education (rated on a 1-5 Likert scale). In
      spring 2003 17 students from the same cohort, 8 immigrants and 9 ethnic Dutch,
      were interviewed extensively on their study experiences in a diverse student
      population. In 2001 the response rate was 90% (277/308), female-male ratio 63%
      (175/102). Non-Western immigrants expected for their medical education more
      benefits from their culture but also more obstacles than ethnic Dutch (p < or =
      0.005). Protestants and Muslims expected more obstacles than the non-religious
      and Catholics (p < or = 0.05). In the interviews three main issues emerged: peer
      training in physical examination in mixed-gender groups, lack of attention to
      student diversity during education, and demand for education in cross-cultural
      medicine. Three incidents of perceived discrimination were reported. The ethnic
      Dutch students interviewed did not socialize much with immigrants, nor did
      students of both groups learn much from one another. Most students favoured mixed
      study groups. The diversity of the population does not seem to have caused
      serious problems, nor has it offered educational benefits. The challenge for
      educators is to provide systematic education in cultural competence and cross
      cultural medicine, in which students and educators indeed practise communication
      across cultural borders.

PMID- 16973450
TI  - Assessing professionalism: theory and practice*.
AB  - Professional attitudes and behaviours have only recently been explicitly
      recognized by medical educators as legitimate and necessary components of global
      competence, although the idea of Fitness to Practice has always presupposed
      acceptable professional behaviour. Medical schools have recently begun to
      introduce teaching and assessment of professionalism, including attitudes and
      behaviours. Partly as a result of the difficulty of assessment in this area,
      selection of students is receiving greater attention, in the pursuit of globally
      competent graduates. However, selection processes may be overrated for this
      purpose. Assessing actual attitudes and behaviour during the course is arguably a
      better way of ensuring that medical graduates are competent in these areas. I
      argue that judgments about attitudinal and behavioural competence are legitimate,
      and need be no more arbitrary than those made about scientific or clinical
      knowledge and skills, but also that these judgments should be restricted to what
      is agreed to be unacceptable behaviour, rather than attempting to rate attitudes
      and behaviour positively. This model introduces students to the way in which
      their behaviours will be judged in their professional lives by registration
      authorities. These theoretical positions are illustrated by a recent case of
      academic failure based on inadequate attitudes and behaviours.

PMID- 16973451
TI  - Twelve tips for developing effective mentors.
AB  - Mentoring is often identified as a crucial step in achieving career success.
      However, not all medical trainees or educators recognize the value of a mentoring
      relationship. Since medical educators rarely receive training on the mentoring
      process, they are often ill equipped to face challenges when taking on major
      mentoring responsibilities. This article is based on half-day workshops presented
      at the 11th Ottawa International Conference on Medical Education in Barcelona on
      5 July 2004 and the annual meeting of the Association of American Medical
      Colleges in Boston on 10 November 2004 as well as a review of literature.
      Thirteen medical faculty participated in the former and 30 in the latter. Most
      participants held leadership positions at their institutions and mentored
      trainees as well as supervised mentoring programs. The workshops reviewed skills
      of mentoring and strategies for designing effective mentoring programs.
      Participants engaged in brainstorming and interactive discussions to: (a) review
      different types of mentoring programs; (b) discuss measures of success and
      failure of mentoring relationships and programs; and (c) examine the influence of
      gender and cultural differences on mentoring. Participants were also asked to
      develop an implementation plan for a mentoring program for medical students and
      faculty. They had to identify student and faculty mentoring needs, and describe
      methods to recruit mentors as well as institutional reward systems to encourage
      and support mentoring.

PMID- 16973452
TI  - Developing a competence-based core curriculum in biomedical laboratory science: a
      Delphi study.
AB  - In this study the Delphi technique has been used to develop a core curriculum for
      education of the biomedical scientist. The rapid development in biomedicine and
      the corresponding changes in methodology in biomedical laboratories demand
      careful planning of the education of biomedical scientists. The Delphi technique
      uses an anonymous panel of experts for suggestions and assessments aiming at
      consensus. Twenty-six experts from different kinds of hospital and university
      laboratories took part in the investigation. They suggested and assessed
      necessary competences for a recently graduated biomedical scientist, and if 75%
      or more of the participants agreed on a competence, it was included in the core
      curriculum. The final list consisted of 66 competences of varying depth, in three
      categories. This list contained several generic competences, concerning for
      example basic laboratory methods, handling of samples, dealing with apparatus and
      applying relevant rules and laws; basic knowledge in chemistry, preclinical
      medicine and laboratory methods; and finally attitudes that the panel expected in
      the recently graduated person. The core was sufficiently restricted to be used in
      a three-year programme and still leave space for about one year of
      electives/special study modules. It became rather traditional, e.g. it did not
      include competences that many recent reports consider important for the future
      professional.

PMID- 16973453
TI  - See one, do one, teach one--exploring the core teaching beliefs of medical school
      faculty.
AB  - This paper explores the core teaching beliefs of medical school faculty and
      establishes whether these beliefs differ among basic science, clinical, and
      instruction specialist faculty. One hundred and twenty-five medical school
      teachers who were members of professional organizations dedicated to the
      improvement of medical school teaching completed a Q-sort of 56 statements
      reflecting their core teaching beliefs. The statements described beliefs about
      motivation, knowledge and skill acquisition, retention, feedback, transfer,
      teacher characteristics, and teaching strategies. Q-sorts were completed by 37
      basic scientists (30% of respondents), 59 clinicians (47%) and 29 instruction
      specialists (23%) working in medical schools. Fifty-two participants were
      classroom teachers (42%), 66 were classroom and clinical teachers (53%), and
      seven reported that they do not teach (6%). The Q-sort results indicate how
      medical school faculty members differ in their core beliefs about teaching and
      learning. Thirty-two respondents (26%) focused on the student as a person first.
      Eight (6%) were content oriented. Thirty-four (27%) were performance oriented;
      their focus was on having students learn and apply knowledge and skills to
      accomplish clinical tasks. Fifty-one respondents (41%) were found to have a blend
      of these viewpoints. Respondents' type of training or type of teaching did not
      provide a reliable indication of core teaching beliefs classification.

PMID- 16973454
TI  - A case study of teaching presence in virtual problem-based learning groups.
AB  - Interest in conducting problem-based learning (PBL) on-line has increased to meet
      student and physician schedules. Little research describes skills needed to
      facilitate PBL on-line. In this paper we studied teaching presence in
      asynchronous PBL groups. Two raters, with average inter-rater agreements of 0.80,
      used an existing code to measure teaching presence in 62 PBL case discussions
      facilitated by one instructor over five years. This instructor was selected
      because of consistently high teaching evaluations. Messages sent by the
      instructor in the on-line PBL discussion were coded into three categories:
      instructional design and organization, facilitating discourse and direct
      instruction. Instructional design indicators were most frequent averaging 22.5
      (SD = 5.6)/discussion. Facilitating discourse and direct instruction were
      comparable, 19.5(SD = 7.4) and 19.5 (SD = 6.7), respectively. Messages and
      indicators of teacher presence rose across time with a decline during subsequent
      PBL cases with the same group.

PMID- 16973455
TI  - Assessing proficiency in adult basic life support: student and expert assessment
      and the impact of video recording.
AB  - Self-assessment is an important aspect in the development of lifelong learning
      skills for medical students, crucial to maintaining a high level of competence in
      practice. Basic Life Support (BLS) is a skill that all health professionals must
      acquire and maintain competence in. This paper reports data from a study of 95
      first-year graduate entry medical students at Flinders University in Australia,
      determining how well the students could assess their own BLS performance. These
      students were videotaped performing a short CPR scenario using a Resusci Anne
      with SkillReporter (Laerdal, Norway). Using a six-point descriptive ratings
      scale, students graded themselves twice: once immediately after completing the
      task, and again after viewing a video of their performance. A single expert
      assessor viewed all the video recordings and, based on International Liaison
      Committee on Resuscitation (ILCOR) Guidelines, graded the students using the same
      scale. The hypothesis was that the intervention of viewing their performance on
      video would improve the correlation of their ratings with the expert assessor.
      The results showed that the students' assessments did not agree with the expert
      assessor either before (weighted kappa = 0.03) or after seeing the video
      (weighted kappa = 0.002). Possible reasons, including student attitudes and lack
      of benchmarking, are discussed. Self-assessment skills of students warrant
      further attention.

PMID- 16973456
TI  - From undergraduate medical education to pre-registration house officer year: how
      prepared are students?
AB  - Studies in the United Kingdom show that the first year of being a new doctor is a
      difficult transition from being an undergraduate medical. These doctors feel ill
      prepared by their undergraduate medical student education and ill-equipped for
      their new role. This is a questionnaire study looking at 193 pre-registration
      house officers (PRHOs) and 212 consultant educational supervisors within the West
      Midlands Deanery in England, UK. The study asked how well prepared these new
      doctors were in seventeen basic subject areas (using a General Medical Council
      based template), and also, using the same template, how well prepared their
      consultant educational supervisors felt they were. Statistical testing included
      ranking of subject areas for each group, reliability testing and comparisons of
      views of house officers and consultants. Both groups ranked communication skills
      areas highest (best prepared) and ranked basic doctoring skills (such as
      prescribing, treatment, decision making and emergencies) lowest. House officers
      rated themselves significantly higher than did their consultant supervisors in
      thirteen out of the seventeen areas tested. In discussion, we ask if we have gone
      too far in teaching effective communication at the expense of basic doctoring
      skills. We also consider whether indeed young doctors have an inflated opinion of
      their own competencies, or are the older generation seeing the world through rose
      tinted spectacles?

PMID- 16973457
TI  - Unprofessional or problematic behaviour of medical students outside the learning
      environment.
AB  - This paper focuses on the question what to do with unprofessional or problematic
      behaviour of medical students outside the learning environment. Examples are
      given to raise awareness of the problem and initiate possible solutions. It is
      advised that medical schools keep an open eye for problematic behaviour outside
      the learning environment, also because documented unprofessional behaviour during
      medical training is a predictor of professional misconduct as a physician. Part
      of this paper was presented by the author as 'Professionalism: between wearing
      blinkers and big brother' at the AMEE conference, Edinburgh, UK, September 2004.

PMID- 16973458
TI  - What to do about medical students with unsatisfactory consultation skills?
AB  - If it is accepted that new doctors must be 'Fit to Practice' in a standard
      clinical house job, they should be competent in basic communication skills.
      Although these skills may be assessed as part of a routine OSCE-style exam in the
      course of the curriculum, the question is raised whether students who fail to
      demonstrate a minimal level of competence in this area should to be allowed to
      progress to the next stage of the course and eventually graduate. This paper
      describes our experiences with introducing 'barrier' stations in communication
      skills into the OSCE. Students who failed these stations, irrespective of their
      overall exam performance, undertook remedial studies in a compulsory two-week
      directed study module followed by a four-station OSCE.

PMID- 16973459
TI  - Design of integrated practice for learning professional competences.
AB  - To acquire professional competences that entail performance of complex skills, an
      authentic learning environment is required focused on the integration of all
      aspects of competences. However, most educational programmes offer separate
      building blocks, such as separate modules for knowledge and skills. Students
      accumulate what they have learned in these modules as they progress through the
      curriculum. In this paper the authors advocate the Four-Component Instructional
      Design model (4C/ID), which offers a whole-task approach to course design for
      programmes in which students learn complex skills. The four core components of
      this approach are: learning tasks, supportive information, just-in-time
      information and part-task practice. A concrete example from medical education
      will be presented to clarify both the general ideas behind this approach and the
      differences between the whole-task approach and conventional educational designs.

PMID- 16973460
TI  - Insights into endoscopy training: a qualitative study of learning experience.
AB  - Endoscopy is an important diagnostic and therapeutic procedure that demands high
      levels of cognitive and technical skill to perform effectively. Surprisingly
      little is known about how endoscopy is best taught and training is often
      inadequate. The aims of this study were to explore the learning experiences of
      endoscopy trainees to improve our understanding of current training. Following
      the use of an initial focus group to generate appropriate themes semi-structured
      interviews were performed on 10 trainees to assess their learning experiences.
      Many different components of the learning experience were identified; one-to-one
      supervised performance forms the basis for teaching but is often sub-optimal;
      endoscopy learners experience anxiety and find re-adopting the role of novice
      difficult; motivation, clear explanation and feedback are crucial to learning;
      breaking down endoscopy training into segments is seen as valuable and as
      learners progress a gradual withdrawal of supervision is appreciated. Several of
      the issues contributing to a positive learning experience relate closely to
      published evidence and theory relating to skills teaching from other fields. A
      model identifying the key elements of endoscopy learning is proposed. Further
      work to apply and test the findings from this study should lead to improved
      endoscopy training.

PMID- 16973461
TI  - Teaching styles of tutors in a problem-based curriculum: students' and tutors'
      perception.
AB  - This study compared the self-rated with student-rated teaching styles of PBL
      tutors. We also examined the relationship between teaching styles of tutors' and
      students' evaluation of tutor effectiveness in tutorials. The study included 48
      tutors and 276 medical students. Tutors, and students' were given a teaching
      style inventory with a 5-point scale consisting of 21 items that comprise four
      domains of teaching styles (facilitative, collaborative, suggestive and
      assertive). In addition, quantitative and qualitative evaluations of tutor
      effectiveness by students were analyzed. Tutors perceived themselves in the
      facilitative-collaborative end of the spectrum of styles In contrast, students
      perceived tutors as less 'facilitative-collaborative' and more 'suggestive
      assertive' than tutors self-ratings (p < 0.001). In addition, the difference in
      perception between students and tutors ratings in the facilitative-collaborative
      domains was more evident as students progressed in the PBL curriculum. The
      students' ratings of the effectiveness of tutors correlated more strongly with
      facilitative-collaborative than with suggestive-assertive domains of teaching
      styles. However, other tutor attributes such as establishing rapport with
      students, providing academic help for them and having content expertise were
      considered important criteria of an effective tutor. We conclude that there is a
      mismatch between students' and tutors' perceptions about teaching styles of
      tutor. Tutor attributes other than teaching styles are important determinants of
      an effective tutor.

PMID- 16973462
TI  - Contextualizing cultural competence training of residents: results of a formative
      research study in Geneva, Switzerland.
AB  - Medical training programs need to prepare physicians to provide care to
      increasingly diverse patient populations. While the general concepts and
      approaches of clinical cultural competence are broadly relevant across contexts,
      the content of cultural competence training should reflect and respond to the
      specific needs and challenges of clinicians in their local reality. In order to
      better understand and respond to the needs and challenges of residents working
      with diverse patients in Geneva, Switzerland, depth interviews with physicians
      and professional medical interpreters and direct observations of consultations
      were combined. Cross-cultural communication difficulties were intertwined with
      more general difficulties related to primary care in an outpatient context, and
      physicians' frustrations reflected the expectations and image of medicine that
      they developed during their hospital-centered training. Study results point to
      the need to understand how cross-cultural communication challenges articulate
      with other aspects of the clinical context.

PMID- 16973463
TI  - The value of a philosophical perspective in teaching the basic medical sciences.
AB  - A major challenge for medical education is the cultivation of practitioners
      capable of embracing both the physico-chemical and transcendent dimensions of
      human life. A widely accepted approach to this dilemma has been the introduction
      of the humanities, and more specifically philosophy, into the medical curriculum.
      The integration of philosophical thinking into the educational process is,
      however, hampered by its apparent incompatibility with the
      scientific/reductionist mindset preeminent in modern medicine. A method of
      presenting relevant philosophic themes within the context of the basic medical
      sciences is proposed. It involves the identification and development of
      philosophic content inherent within the scientific subjects that we teach.

PMID- 16973464
TI  - Remaining in or leaving the profession: the view of medical students.
AB  - Views held by medical students on their remaining in a medical career or leaving
      it and the relationship with other elements of becoming a doctor are described.
      The study was carried out with a self-administered questionnaire with general
      medical students randomly selected in Hungary. Depending on whether they want to
      remain in the profession or want to leave it, medical students were divided into
      two groups. A significant difference was revealed between the two groups with
      regard to the strength of their dedication to the profession. The medical
      students indicated that their decision to leave or stay with medicine is
      conditioned by subjective factors. Our results could contribute to shaping of a
      better professional identity during training/socialisation, as well as to a
      better understanding of job abandoners.

PMID- 16973465
TI  - Understanding the internet-based distance learning preferences of European
      respiratory specialists.
AB  - We studied the learning preferences of 160 respiratory specialists from four
      European countries who participated in ten internet-based learning modules and
      answered linked survey questions. Specialists were enthusiastic for internet
      learning amongst all national groups and particularly wanted to access material
      for teaching others. The value of social interactive learning was acknowledged
      but British and German subjects appeared more reluctant to participate. Internet
      delivered distance learning is well perceived amongst respiratory specialists.
      There is potential for both individual and group learning that could be realized
      by developing Europe-wide continuing professional development communities.

PMID- 16973466
TI  - What do medical students learn from early clinical experiences (ECE)?
AB  - What are the common learning themes perceived by medical students during ECE with
      varying practice settings and patient profiles? Retrospective qualitative and
      quantitative analyses of structured descriptive reports completed by one class (n
      = 92) for 895 observed patient encounters identified common learning themes.
      Identified themes were examined by practice setting and patient characteristics.
      Student response rates were 85 to 94% across settings. Fifty-five percent of ECE
      were in outpatient settings. Chief complaints were predominantly medical (67%);
      only 20% represented psychosocial and 8% preventive care, respectively (5% were
      ambiguous). The five most common learning themes (out of 13 themes coded) were
      communication (>50%), procedures/time management, cross-cultural issues, feeling
      useful as a student, and presenting medical problems. Cross-cultural issues were
      addressed mainly in community settings. Negative learning occurred only rarely
      (<3%). Student observations from ECE can be used by course managers to design
      effective early clinical exposures to address specific course learning
      objectives.

PMID- 16973468
TI  - Guidelines for using Lance Armstrong's novel to teach cytotoxic drugs.

PMID- 16973469
TI  - The effect of different teaching methods on final year medical students' skills
      in examining arteries and veins.

PMID- 16973470
TI  - Benefits and drawbacks of implementation of PBL elements into a new course on
      applied pharmacotherapy.

PMID- 16973471
TI  - Patient crying in hospitals: a survey on undergraduate nursing and medical
      students.

PMID- 16973474
TI  - E-learning and all that jazz.

PMID- 16973475
TI  - Jottings by Saquarrah.

PMID- 16973476
TI  - New directions in liquid crystal science.
AB  - While we are all familiar with liquid crystal displays, an industry currently
      worth more than US dollars 60 billion yr(-1) and growing rapidly, fewer people
      are aware of the breadth of the subject of liquid crystals--one that represents
      the study of the fourth state of matter. Liquid crystals are found as essential
      elements in biological systems, soaps and detergents, sensor technologies and in
      the manipulation of electromagnetic radiation of various wavelengths. This
      meeting was designed to highlight both the truly multidisciplinary nature of
      liquid crystal science and to feature those areas away from electro-optic
      displays; these issues are developed and summarized in more detail.

PMID- 16973477
TI  - Cationic liposome-DNA complexes: from liquid crystal science to gene delivery
      applications.
AB  - At present, there is an unprecedented level of interest in the properties and
      structures of complexes consisting of DNA mixed with oppositely charged cationic
      liposomes (CLs). The interest arises because the complexes mimic natural viruses
      as chemical carriers of DNA into cells in worldwide human gene therapy clinical
      trials. However, since our understanding of the mechanisms of action of CL-DNA
      complexes interacting with cells remains poor, significant additional insights
      and discoveries will be required before the development of efficient chemical
      carriers suitable for long-term therapeutic applications. Recent studies describe
      synchrotron X-ray diffraction, which has revealed the liquid crystalline nature
      of CL-DNA complexes, and three-dimensional laser-scanning confocal microscopy,
      which reveals CL-DNA pathways and interactions with cells. The importance of the
      liquid crystalline structures in biological function is revealed in the
      application of these modern techniques in combination with functional
      transfection efficiency measurements, which shows that the mechanism of gene
      release from complexes in the cell cytoplasm is dependent on their precise liquid
      crystalline nature and the physical and chemical parameters (for example, the
      membrane charge density) of the complexes. In [section sign] 5, we describe some
      recent new results aimed at developing bionanotube vectors for gene delivery.

PMID- 16973478
TI  - Degradative transport of cationic amphiphilic drugs across phospholipid bilayers.
AB  - Drug molecules must cross multiple cell membrane barriers to reach their site of
      action. We present evidence that one of the largest classes of pharmaceutical
      drug molecules, the cationic amphiphilic drugs (CADs), does so via a catalytic
      reaction that degrades the phospholipid fabric of the membrane. We find that CADs
      partition rapidly to the polar-apolar region of the membrane. At physiological
      pH, the protonated groups on the CAD catalyse the acid hydrolysis of the ester
      linkage present in the phospholipid chains, producing a fatty acid and a single
      chain lipid. The single-chain lipids rapidly destabilize the membrane, causing
      membranous fragments to separate and diffuse away from the host. These membrane
      fragments carry the drug molecules with them. The entire process, from drug
      adsorption to drug release within micelles, occurs on a time-scale of seconds,
      compatible with in vivo drug diffusion rates. Given the rate at which the
      reaction occurs, it is probable that this process is a significant mechanism for
      drug transport.

PMID- 16973479
TI  - Are liquid crystalline properties of nucleosomes involved in chromosome structure
      and dynamics?
AB  - Nucleosome core particles correspond to the structural units of eukaryotic
      chromatin. They are charged colloids, 101 Angstrom in diameter and 55 Angstrom in
      length, formed by the coiling of a 146/147 bp DNA fragment (50 nm) around the
      histone protein octamer. Solutions of these particles can be concentrated, under
      osmotic pressure, up to the concentrations found in the nuclei of living cells.
      In the presence of monovalent cations (Na(+)), nucleosomes self-assemble into
      crystalline or liquid crystalline phases. A lamello-columnar phase is observed at
      'low salt' concentrations, while a two-dimensional hexagonal phase and a three
      dimensional quasi-hexagonal phase form at 'high salt' concentrations. We followed
      the formation of these phases from the dilute isotropic solutions to the ordered
      phases by combining cryoelectron microscopy and X-ray diffraction analyses. The
      phase diagram is presented as a function of the monovalent salt concentration and
      applied osmotic pressure. An alternative method to condense nucleosomes is to
      induce their aggregation upon addition of divalent or multivalent cations
      (Mg(2+), spermidine(3+) and spermine(4+)). Ordered phases are also found in the
      aggregates. We also discuss whether these condensed phases of nucleosomes may be
      relevant from a biological point of view.

PMID- 16973480
TI  - Pressure-jump X-ray studies of liquid crystal transitions in lipids.
AB  - In this paper, we give an overview of our studies by static and time-resolved X
      ray diffraction of inverse cubic phases and phase transitions in lipids. In
      [section sign] 1, we briefly discuss the lyotropic phase behaviour of lipids,
      focusing attention on non-lamellar structures, and their geometric/topological
      relationship to fusion processes in lipid membranes. Possible pathways for
      transitions between different cubic phases are also outlined. In [section sign]
      2, we discuss the effects of hydrostatic pressure on lipid membranes and lipid
      phase transitions, and describe how the parameters required to predict the
      pressure dependence of lipid phase transition temperatures can be conveniently
      measured. We review some earlier results of inverse bicontinuous cubic phases
      from our laboratory, showing effects such as pressure-induced formation and
      swelling. In [section sign] 3, we describe the technique of pressure-jump
      synchrotron X-ray diffraction. We present results that have been obtained from
      the lipid system 1:2 dilauroylphosphatidylcholine/lauric acid for cubic-inverse
      hexagonal, cubic-cubic and lamellar-cubic transitions. The rate of transition was
      found to increase with the amplitude of the pressure-jump and with increasing
      temperature. Evidence for intermediate structures occurring transiently during
      the transitions was also obtained. In [section sign] 4, we describe an IDL-based
      'AXcess' software package being developed in our laboratory to permit batch
      processing and analysis of the large X-ray datasets produced by pressure-jump
      synchrotron experiments. In [section sign] 5, we present some recent results on
      the fluid lamellar-Pn3m cubic phase transition of the single-chain lipid 1
      monoelaidin, which we have studied both by pressure-jump and temperature-jump X
      ray diffraction. Finally, in [section sign] 6, we give a few indicators of future
      directions of this research. We anticipate that the most useful technical advance
      will be the development of pressure-jump apparatus on the microsecond time-scale,
      which will involve the use of a stack of piezoelectric pressure actuators. The
      pressure-jump technique is not restricted to lipid phase transitions, but can be
      used to study a wide range of soft matter transitions, ranging from protein
      unfolding and DNA unwinding and transitions, to phase transitions in thermotropic
      liquid crystals, surfactants and block copolymers.

PMID- 16973481
TI  - Relationships between molecular structure and physical properties in bent-core
      mesogens.
AB  - New five-ring bent-core mesogens that possess only ester connecting groups
      between the aromatic rings and different lateral substituents at the central
      phenyl ring are presented. The mesophases have been assigned by polarizing
      microscopy, differential scanning calorimetry, X-ray diffraction and electro
      optical measurements. It is shown that the mesophase behaviour depends strongly
      on the position of the lateral substituents. Compounds, which are derived from 4
      cyano-, 4-chloro- and 4,6-dichloro-resorcinol, show polymorphism variants where
      polar phases (SmAP, SmCP) occur together with nematic and conventional smectic
      phases, e.g. SmA-SmAP, SmA-SmC(S)P(A)-Col(ob)-SmC(S)P(A), N-SmA-SmCP(A), SmA-SmC
      SmCP(A) and SmC-SmCP(A). On the basis of the behaviour of two series of
      materials, the occurrence of different polar-switching mechanisms could be
      demonstrated. Apart from the usual mechanism by director rotation around the tilt
      cone, the polar switching can also take place through collective rotation of the
      molecules around their long axes, which corresponds to a field-induced switching
      of the layer chirality. A remarkable finding is the polar switching in the
      crystalline modification of long-chain, bent-core compounds with a methyl group
      in 2-position, which is accompanied by a clear change of the optical texture and
      by a relatively high switching polarization (approx. 600 nC cm(-2)). It was found
      for selected bent-core compounds that, above the transition temperature of a
      polar to a non-polar phase, the non-polar phase can be transformed to the polar
      phase by application of an electric field, which was proved for the transitions
      isotropic-SmCP(F), SmA-SmCP(F) and isotropic-CrII polar.

PMID- 16973482
TI  - Uniaxial and biaxial nematic liquid crystals.
AB  - The unusual exhibition of a biaxial nematic phase in nonlinear thermotropic
      mesogens derived from the 2,5-oxadiazole biphenol (ODBP) core is placed in a
      general context; the uniaxial nematic phase of the prototypical rod-like mesogen
      para-quinquephenyl does not follow the classical mean-field behaviour of
      nematics, thus questioning the utility of such theories for quantitative
      predictions about biaxial nematics. The nuclear magnetic resonance spectra of
      labelled probe molecules dissolved in ODBP biaxial nematic phases suggest that a
      second critical rotation frequency, related to the differences in the transverse
      diamagnetic susceptibilities of the biaxial nematic, must be exceeded in order to
      create an aligned two-dimensional powder sample. Efforts to find higher viscosity
      and lower temperature biaxial nematics (with lower critical rotation rates) to
      confirm the above conjecture are described. Several chemical modifications of the
      ODBP mesogenic core are presented.

PMID- 16973483
TI  - The effect of size and shape variation in discotic liquid crystals based on
      triphenylene cores.
AB  - The triphenylene core provides a versatile platform from which discotic liquid
      crystals can be constructed. Synthetic advances permit the effect that
      substantial or subtle variation on structure has on mesophase formation. Through
      comparison of many derivatives, from our studies and others, it appears that the
      discotic core should be viewed as the triphenylene unit plus the attached
      polarizable substituents. Disruption of these extended cores discourages
      mesophase formation.

PMID- 16973484
TI  - Bioinspired supramolecular liquid crystals.
AB  - A brief account on the historical events leading to the discovery of self
      assembling dendrons that generate self-organizable supramolecular dendrimers, or
      supramolecular polymers, and self-organizable dendronized polymers is provided.
      These building blocks were accessed by an accelerated design strategy that
      involves structural and retrostructural analysis of periodic and quasi-periodic
      assemblies. This design strategy mediated the discovery of porous helical
      supramolecular structures that self-assembled from dendritic dipeptides. Helical
      porous columns are the closest mimics of biologically related structures, such as
      tobacco mosaic virus coat, porous transmembrane proteins, porous pathogens and
      antibiotics. It is expected that this concept will allow one to investigate the
      structural origin of functions in synthetic supramolecular materials.

PMID- 16973485
TI  - Non-display applications and the next generation of liquid crystal over silicon
      technology.
AB  - The next generation of applications for liquid crystal (LC) over silicon
      technology will be non-display oriented systems such as adaptive optical
      interconnects, optical switches and optical image processors. These new non
      display applications have a different set of material parameters, which means
      that existing display-based materials are not entirely optimal. This is
      particularly the case when the application is driven by phase modulation at high
      frame rates (more than 1 kHz). An example of such a non-display application is in
      adaptive optical interconnects. Optical data transmission between printed circuit
      boards is becoming more and more important as the data rate in electronic systems
      increases into the gigahertz region. One way of avoiding the data bottlenecks in
      board to board interconnects is to use optical links to transmit the data. Recent
      research into free-space optical links has shown that a high level of
      manufacturing tolerance must be used to maintain the link. However, one way of
      avoiding these limitations is to use a reconfigurable LC phase hologram as a beam
      steering element to compensate for movement between the boards and maintain the
      optical data path.

PMID- 16973486
TI  - Metal slits and liquid crystals at microwave frequencies.
AB  - While the use of liquid crystals (LCs) over the visible region is ubiquitous in
      flat-screen displays, there has been little by the way of applications at other
      wavelengths. Specifically, notwithstanding the continuing permittivity anisotropy
      to be found at longer wavelengths, there has been virtually no development in the
      microwave domain. This is largely due to the fact that scaling up the micrometer
      thick LC layers used for visible radiation to millimetre dimensions is seen as
      impractical. In this study, it is shown how, using thin slits in metal
      structures, a completely new generation of LC devices for use at microwaves may
      be realized. Such structures include slatted metal Fabry-Perot resonators, beam
      steering devices, thin flexible voltage tunable filters and even cascade
      structures with strongly enhanced and reshaped microwave fields.

PMID- 16973487
TI  - Photonics and lasing in liquid crystal materials.
AB  - Owing to fundamental reasons of symmetry, liquid crystals are soft materials.
      This softness allows long length-scales, large susceptibilities and the existence
      of modulated phases, which respond readily to external fields. Liquid crystals
      with such phases are tunable, self-assembled, photonic band gap materials; they
      offer exciting opportunities both in basic science and in technology. Since the
      density of photon states is suppressed in the stop band and is enhanced at the
      band edges, these materials may be used as switchable filters or as mirrorless
      lasers. Disordered periodic liquid crystal structures can show random lasing. We
      highlight recent advances in this rapidly growing area, and discuss future
      prospects in emerging liquid crystal materials. Liquid crystal elastomers and
      orientationally ordered nanoparticle assemblies are of particular interest.

PMID- 16973488
TI  - Artificial muscles based on liquid crystal elastomers.
AB  - This paper presents our results on liquid crystal (LC) elastomers as artificial
      muscle, based on the ideas proposed by de Gennes. In the theoretical model, the
      material consists of a repeated series of main-chain nematic LC polymer blocks,
      N, and conventional rubber blocks, R, based on the lamellar phase of a triblock
      copolymer RNR. The motor for the contraction is the reversible macromolecular
      shape change of the chain, from stretched to spherical, that occurs at the
      nematic-to-isotropic phase transition in the main-chain nematic LC polymers. We
      first developed a new kind of muscle-like material based on a network of side-on
      nematic LC homopolymers. Side-on LC polymers were used instead of main-chain LC
      polymers for synthetic reasons. The first example of these materials was thermo
      responsive, with a typical contraction of around 35-45% and a generated force of
      around 210 kPa. Subsequently, a photo-responsive material was developed, with a
      fast photochemically induced contraction of around 20%, triggered by UV light. We
      then succeeded in preparing a thermo-responsive artificial muscle, RNR, with
      lamellar structure, using a side-on nematic LC polymer as N block.Micrometre
      sized artificial muscles were also prepared. This paper illustrates the bottom-up
      design of stimuli-responsive materials, in which the overall material response
      reflects the individual macromolecular response, using LC polymer as building
      block.

PMID- 16973489
TI  - Designing solution-processable air-stable liquid crystalline crosslinkable
      semiconductors.
AB  - Organic electronics technology, in which at least the semiconducting component of
      the integrated circuit is an organic material, offers the potential for
      fabrication of electronic products by low-cost printing technologies, such as ink
      jet, gravure offset lithography and flexography. The products will typically be
      of lower performance than those using the present state of the art single crystal
      or polysilicon transistors, but comparable to amorphous silicon. A range of
      prototypes are under development, including rollable electrophoretic displays,
      active matrix liquid crystal (LC) displays, flexible organic light emitting diode
      displays, low frequency radio frequency identification tag and other low
      performance electronics. Organic semiconductors that offer both electrical
      performance and stability with respect to storage and operation under ambient
      conditions are required. This work describes the development of reactive mesogen
      semiconductors, which form large crosslinked LC domains on polymerization within
      mesophases. These crosslinked domains offer mechanical stability and are inert to
      solvent exposure in further processing steps. Reactive mesogens containing
      conjugated aromatic cores, designed to facilitate charge transport and provide
      good oxidative stability, were prepared and their liquid crystalline properties
      evaluated. The organization and alignment of the mesogens, both before and after
      crosslinking, were probed by grazing incidence wide-angle X-ray scattering of
      thin films. Both time-of-flight and field effect transistor devices were prepared
      and their electrical characterization reported.

PMID- 16973490
TI  - Laser manipulation in liquid crystals: an approach to microfluidics and
      micromachines.
AB  - Laser trapping of particles in three dimensions can occur as a result of the
      refraction of strongly focused light through micrometre-sized particles. The use
      of this effect to produce laser tweezers is extremely common in fields such as
      biology, but it is only relatively recently that the technique has been applied
      to liquid crystals (LCs). The possibilities are exciting: droplets of LCs can be
      trapped, moved and rotated in an isotropic fluid medium, or both particles and
      defects can be trapped and manipulated within a liquid crystalline medium. This
      paper considers both the possibilities. The mechanism of transfer of optical
      angular momentum from circularly polarized light to small droplets of nematic LCs
      is described. Further, it is shown that droplets of chiral LCs can be made to
      rotate when illuminated with linearly polarized light and possible mechanisms are
      discussed. The trapping and manipulation of micrometre-sized particles in an
      aligned LC medium is used to provide a measure of local shear viscosity
      coefficients and a unique test of theory at low Ericksen number in LCs.

PMID- 16973491
TI  - Gelation versus liquid crystal phase transitions in suspensions of plate-like
      particles.
AB  - Gelation is a common effect in aqueous suspensions of charged colloidal clay
      platelets at concentrations as low as 1 wt%. However, in systems of charged
      gibbsite [Al(OH)3] platelets, gelation can be delayed to concentrations as high
      as 50 wt% depending on the ionic strength. We investigated the phase behaviour of
      this system approaching the state of gelation in the delicate region between
      attractive and repulsive states that originate from competition between Coulomb
      repulsion and van der Waals attraction. As a function of the ionic strength,
      isotropic-nematic, nematic-columnar and isotropic-columnar phase separations were
      observed. Moreover, compression by gravitational forces allowed us to observe
      phase separation that is arrested by gelation in the homogeneous suspensions.

PMID- 16973492
TI  - Silica nanocasting of lyotropic surfactant phases and organized organic matter:
      material science or an analytical tool?
AB  - The synthesis of porous inorganic films and materials by templating organized
      organic matter with nanosized structural elements is an actual field in the cross
      section of inorganic chemistry, materials chemistry and surfactant science. This
      discussion article will review recent experiments in this area on a variety of
      systems and try to evaluate the outcome of both material applications and the
      basic understanding of self-assembly processes of organic self-organization.

PMID- 16973494
TI  - Effects of raloxifene on platelet functions in patients with postmenopausal
      osteoporosis.
AB  - Many studies have addressed the effects of estrogenic compounds on platelet
      function. Raloxifene is a selective estrogen receptor modulator (SERM), which is
      currently used for the treatment of postmenopausal osteoporosis. At present,
      there are no clinical data about the effects of raloxifene on platelet function.
      The purpose of this study was to determine if raloxifene at therapeutic doses
      affects platelet function in patients with postmenopausal osteoporosis. The
      effects of raloxifene on platelet function were investigated using a commercial
      platelet function analyzer (PFA-100) with collagen epinephrine and collagen
      adenosine 5'-diphosphate (ADP) cartridges. We studied platelet function of 30
      patients with postmenopausal osteoporosis before and 15 days after initiation of
      raloxifene 60 mg/daily. Closure times did not differ significantly between
      samples obtained before (117.8 +/- 20.5 s) and after raloxifene therapy (106.5 +/
      25.4 s) in collagen/epinephrine cartridges (P > 0.05). There was also no
      statistically significant difference in mean closure times with collagen/ADP
      cartridges at baseline (86.2 +/- 18.5 s) and after raloxifene therapy (84.4 +/-
      13.8 s) (P > 0.05). Platelet counts (278.3 +/- 72.9 vs. 262.4 +/- 56.7 109/L, P >
      0.05) and mean platelet volumes (8.9 +/- 1 vs. 9.1 +/- 1 fL, P > 0.05) were not
      different before and after raloxifene therapy. Although estrogen related
      compounds do affect platelet function, there is suggestive data in our study that
      raloxifene in therapeutic dose exhibit no effect on platelet function in patients
      with postmenopausal osteoporosis.

PMID- 16973495
TI  - Antioxidant and antiaggregatory effects of an extract from Conyza canadensis on
      blood platelets in vitro.
AB  - The antioxidative activity of the polysaccharide extract from Conyza canadensis
      in blood platelets treated with peroxynitrite (ONOO-) was studied. Peroxynitrite
      as a strong biological oxidant has toxic effects on blood platelets and induces
      the oxidation of thiols, carbonylation and nitration of platelet proteins and
      lipid peroxidation. Therefore, the aim of our study was to assess if the natural
      extract from herbal plant, Conyza Canadensis, may protect platelet proteins
      against nitrative and oxidative damage induced by ONOO-. In our study we measured
      oxidative damage of platelet proteins induced by peroxynitrite and protectory
      effects of this extract by estimation of the level of carbonyl groups and
      nitrotyrosine (a marker of platelet protein nitration). We also used cytochrome c
      reduction method to test the ability of this extract to change O2-* generation in
      platelets. Moreover, we determined the effects of the extract on blood platelet
      aggregation induced by ADP. We observed that the extract from Conyza canadensis
      distinctly reduced oxidation and nitration of proteins in blood platelets treated
      with ONOO-(0.1mM) and O2-* production in these cells. The extract from Conyza
      canadensis also inhibited platelet aggregation. The ability of the extract to
      decrease O2-* generation in blood platelets supports the importance of free
      radicals in platelet functions, including aggregation process. The present study
      suggests that the natural polysaccharide extract from Conyza canadensis has
      antiaggregatory and antioxidative activities, and therefore may be beneficial in
      the prevention of peroxynitrite-related diseases, such as cardiovascular or
      inflammatory diseases.

PMID- 16973496
TI  - The effect of exercise and training status on platelet activation: do cocoa
      polyphenols play a role?
AB  - Sedentary and trained men respond differently to the same intensity of exercise,
      this is probably related to their platelet reactivity and antioxidant capacity.
      There is growing interest in the utilization of antioxidant-rich plant extracts
      as dietary food supplements. The aim of this study was to investigate the effect
      of an acute bout of sub maximal exercise on platelet count and differential
      response of platelet activation in trained and sedentary subjects and to observe
      if cocoa polyphenols reverse the effect of exercise on platelet function. The
      practical significance of this study was that many sedentary people engage in
      occasional strenuous exercise that may predispose them to risk of heart disease.
      Fasting blood samples were collected from 16 male subjects, pre and post 1-h
      cycling exercise at 70% of maximal aerobic power (VO2max) before and after
      consumption of cocoa or placebo. Agonist stimulated citrated whole blood was
      utilized for measuring platelet aggregation, adenosine triphosphate (ATP) release
      and platelet activation. Baseline platelet count (221 +/- 33 x 10(9)/L) and ATP
      release (1.4 +/- 0.6 nmol) increased significantly (P < 0.05) after exercise in
      all subjects. Baseline platelet numbers in the trained were higher (P < 0.05)
      than in the sedentary (235 +/- 37 vs. 208 +/- 34 x 10(9)/L), where as platelet
      activation in trained was lower (P < 0.05) than sedentary (51 +/- 6 vs. 59 +/-
      5%). Seven days of cocoa polyphenol supplementation had little effect on any of
      the parameters measured. We conclude that trained subjects show decreased
      activation of stimulated platelets when compared to the sedentary subjects and
      short-term cocoa polyphenol supplementation did not decrease platelet activity in
      response to exercise independent of prior training status.

PMID- 16973497
TI  - Calcium-sensitive mitochondrial membrane potential in human platelets and
      intrinsic signals of cell death.
AB  - The mechanisms involved in storage-induced damage in platelets are not well
      understood, but membrane signalling via Ca2+ ion flux may affect mitochondrial H+
      gradients and metabolism and the intrinsic pathways of cell death, platelet
      survival and function. In this study, the effects of blood bank storage
      conditions, including reduced plasma concentration and interrupted agitation,
      were evaluated in platelets from 136 healthy donors. Mitochondrial membrane
      potential (DeltaPsim), an indicator of intrinsic cell death, and its sensitivity
      to Ca2+ ionophore A23187, were monitored using JC-1 by flow cytometry and
      fluorescence microscopy. Platelet survival was examined using lactate
      dehydrogenase release, annexin V binding and caspase-3/7 activity. Decreased
      plasma concentration and interrupted agitation affected DeltaPsim and caspase
      3/7. Over 7 days in 30% plasma DeltaPsim showed a significant reduction (86.3 +/-
      1.1% platelets with polarised mitochondria day 1; 79.9 +/- 2.1% day 5; 75.1 +/-
      3.8% day 7, P = 0.01 day 1 vs. day 7). Whilst DeltaPsim in agitated platelets in
      100% plasma was unchanged up to day 7, interruption of agitation was associated
      with a 44% reduction in the proportion of platelets with polarised mitochondria
      after 5 days (56 +/- 11%). The Ca2+ sensitivity of DeltaPsim changed earlier: 5
      microM A23187 caused a 20-30% change in the fraction of platelets with polarised
      mitochondria by day 5. Ca2+ sensitivity also increased during interrupted
      agitation and reduced plasma concentration. DeltaPsim also correlated with
      indicators of platelet death, caspase-3 activity and annexin V binding
      (correlation coefficients of 0.8). In conclusion, changes in Ca2+-sensitive
      DeltaPsim are involved in the initiation of storage-induced cell death signals
      that influence platelet count and function in vivo.

PMID- 16973498
TI  - Platelet-dependent coagulation assays for factor VIII efficacy measurement after
      substitution therapy in patients with haemophilia A.
AB  - FVIII therapy for haemophilia A is safe and effective, with the problem of
      individually sufficient efficacy unsettled. Routine one-stage clotting assays and
      tests employing chromogenic substrates poorly detect individual haemostatic
      effects of FVIII due to artificial test conditions. In particular, the use of
      cell-free and diluted plasma samples neglect the crucial role of platelets for
      thrombin and fibrin formation. To optimize FVIII substitution therapy, we
      measured in 40 patients with severe to mild haemophilia A before and after FVIII
      substitution the FVIII activity in cell-free plasma samples using a one-stage
      clotting assay as well a chromogenic substrate assay and compared the data with
      those obtained with cell-based coagulation tests, i.e. thrombin generation in
      platelet-rich plasma (PRP) and thromboelastography (TEG) in samples of citrated
      whole blood (WB). To determine the maximum ex vivo haemostatic effect we added 1
      unit/ml of FVIII to samples of PRP and WB and measured the maximum thrombin
      generation in the thrombin generation test (TGT) and the maximum clot firmness
      (MCF) in TEG. After FVIII substitution we observed a nearly linear relation
      between the individual FVIII activities administered to the patients and the
      activities measured in the plasma samples. However, data obtained with TGT and
      TEG revealed a high inter-individual variation and a very poor correlation to the
      administered FVIII activity. Actually, it could be shown that FVIII substitution
      yielding in a FVIII plasma activity of about 30% is sufficient to get an ex vivo
      haemostatic effect of more that 90% as measured by maximum thrombin generation
      and MCF. FVIII substitution up to a plasma activity of more than 90% did not
      further enhance the haemostatic effect. Our data clearly demonstrate that the
      haemostatic effect of FVIII is not only dependent on the activity that is
      measured in plasma but also depends on the interplay between coagulation and
      blood cells, in particular with platelets. The use of cell-based coagulation
      tests such us TGT or TEG may help to optimize FVIII therapy by determining the
      individual FVIII dosage that produces a maximum haemostatic effect.

PMID- 16973499
TI  - Thromboelastography: potential bedside tool to assess the effects of antiplatelet
      therapy?
AB  - Modified thrombelastography (TEG) is a simple point of care test that provides an
      overall assessment of ex vivo clot formation and currently has limited clinical
      application. We evaluated the ability of TEG to assess the effects of
      antiplatelet therapy on clot formation using a novel assessment parameter (the
      area under curve). Forty healthy volunteers were divided into four groups of 10.
      Group A took aspirin 75 mg once daily for 7 days followed by aspirin 75 mg and
      clopidogrel 75 mg once daily in combination for 7 more days. Blood samples were
      taken for analysis at day 0 and days 7 and 14. Group B took a single 300 mg dose
      of aspirin. Group C took 600 mg of clopidogrel only. Group D took 300 mg of
      aspirin and 600 mg of clopidogrel at the same time. For groups B, C and D blood
      was taken prior to drug administration and at 2, 6 and 24 h afterwards. Each
      sample was tested by TEG in four channels following activation using (1) kaolin,
      (2) activator F (Act F), a direct activator of fibrin, (3) Act F + arachidonic
      acid (AA) and (4) Act F + adenosine diphosphate (ADP). Parameters measured
      included the maximum amplitude (MA) of the clot and the area under the TEG
      generated curve at 1 h. Significant, time-dependent reductions in MA and area
      were seen in the AA-activated samples following administration of aspirin in all
      groups as compared to baseline. By contrast, there were no significant
      differences in MA or area in the AA-activated samples with clopidogrel alone.
      Significant reductions were also seen in MA and area in ADP-activated samples
      from volunteers treated with clopidogrel as compared to baseline. Three out of 10
      subjects receiving 600 mg clopidogrel had a reduction in their responses of 30%
      or less, thus identifying them as relatively resistant to the drug. This study
      identifies a rapid, reliable method for assessing the time-dependent effects of
      antiplatelet therapy on clotting using a novel parameter of area of the TEG
      trace, which could have an important clinical application as a point of care test
      of efficacy, particularly in the context of acute coronary syndromes and
      percutaneous coronary intervention.

PMID- 16973500
TI  - Suitability of measurement of swirling as a marker of platelet shape change in
      concentrates stored for transfusion.
AB  - Platelet discoid shape is known to correlate with in vivo viability after
      transfusion. Measurement of shape change requires invasive sampling and laborious
      assays, which is difficult to perform in a blood transfusion center as a routine
      test for quality control of stored platelets. The objective of this study was to
      establish suitability of swirling assessment in stored platelet suspension as a
      routine test for quality check, by comparing platelet shape change measurement
      carried out in parallel. The study was done in two types of bags obtained from
      different manufactures (Groups 1 and 2). Platelet concentrates (PC) were stored
      for 120 h and samples drawn at 24-h intervals, optical analysis at 540 nm was
      carried out to quantify shape change in response to an agonist adenosine
      diphosphate (ADP). The same bags were subjected to swirling assessment, by two
      blood bank personnel independently and graded as positive (+, ++, +++) or as
      negative, based on the silky appearance of the suspension. Swirling negative
      platelets were prepared by storing platelets at 4 degrees C for 24 h and were
      compared with swirling positive platelets. Other parameters studied in the
      samples drawn at 24-h intervals were platelet count, mean platelet volume, and
      blood gases. Swirling assessment results correlated well with shape change
      measurement at each study period with a P value significant at 0.02 and 0.04 for
      group 1 and 2 bags, respectively. In the negative swirling controls, extent of
      shape change was lower than the extent in test bags, showing reduced capacity to
      respond to ADP at 4 degrees C. The results of the study indicate that by simple
      swirling measurements, stored PC can be monitored for loss of discoid shape
      before they are transfused. Gas tension and pH were with in permissible limits.
      Therefore, inspection of swirling can be a reliable method of quality control as
      it correlates with platelet function. The platelets that retain the discoid shape
      in vitro at the time of transfusion are expected to be functional in vivo.

PMID- 16973501
TI  - Do heterotrimeric G proteins redistribute upon G protein-coupled receptor
      stimulation in platelets?
AB  - Previous studies have proposed that stimulation of G protein-coupled receptors
      can cause a redistribution of G proteins to other receptors. The redistribution
      would cause a greater functional sensitivity of unsensitized 'secondary'
      receptors toward their agonists. Using platelets as a model system, we utilized a
      proximal signaling event, intracellular calcium mobilization, to determine if
      agonist stimulation of particular Gq-coupled receptors would result in increased
      sensitivity for stimulation of other Gq-coupled receptors. Platelets express
      three Gq-coupled receptors for thrombin, thromboxane A2, and ADP with different
      potencies. Varying concentrations of a primary agonist (PAR-1 agonist SFLLRN, or
      the TXA2 agonist U46619) was followed by a constant submaximal concentration of a
      secondary agonist (U46619, or the P2Y1 agonist ADP). We observed that initial
      stimulation by SFLLRN was followed by a decrease in the extent of secondary
      U46619 or ADP-mediated calcium mobilization in comparison to control responses
      (i.e. without primary stimulation). To extend these studies we examined calcium
      mobilization in platelets from mice that were either wild-type or homozygous null
      for the PAR-4 or P2Y1 receptors, hypothesizing that the loss of PAR-4 or P2Y1
      receptors would cause redistribution of its Galphaq proteins to other receptors,
      and elicit a greater response when stimulated with other agonists than in
      platelets from a wild-type mouse. However, our results showed almost identical
      levels of peak calcium between wild-type or PAR-4 null mice when stimulated with
      either ADP or U46619. Similar results were obtained for the P2Y1 null mice
      stimulated with AYPGKF or U46619. We conclude that stimulation of one Gq coupled
      receptor does not result in redistribution of Gq to other Gq-coupled receptors.

PMID- 16973502
TI  - Regulation of cytosolic PlA2 activity by PP1/PP2A serine/threonine phosphatases
      in human platelets.
AB  - Platelet thromboxane A2 (TXA2) synthesis is an important pathway of platelet
      reactivity. We report that in thrombin-stimulated platelets, PP1/PP2A
      serine/threonine phosphatases regulate phospholipase A2 (cPLA2) activity, which
      is required for TXA2 synthesis. Two mechanisms are involved: (a) constitutively
      active PP1/PP2A regulate cPLA2 phosphorylation, and (b) PP1/PP2A activity
      mediates agonist-induced increase in cytosolic Ca2+ ([Ca2+]i). Inhibition of
      PP1/PP2A with okadaic acid (OA) induces cPLA2 phosphorylation but reduces Ca2+
      responses: release from intracellular stores and influx through the plasma
      membrane, particularly that mediated by store-mediated Ca2+ entry (SMCE). A
      significant correlation (r = 0.64) exists between OA-regulated [Ca2+]i and TXA2
      synthesis. Okadaic acid-induced decrease in SMCE and the associated TXA2
      synthesis are mediated by a reduction in protein-tyrosine phosphorylation. This
      reduction is not due to inhibition of tyrosine kinases but rather to an OA
      mediated increase in tyrosine phosphatases. This is the first study to report
      that PP1/PP2A phosphatases are involved in the regulation of the two key elements
      in eicosanoid synthesis, [Ca2+]i and cPLA2 phosphorylation. Moreover, PP1/PP2A
      regulation of [Ca2+]i and tyrosine phosphorylation may be important for other
      calcium-dependent processes and/or signal transduction mechanisms in platelets.

PMID- 16973503
TI  - Comparison of changes in circulating platelet-derived microparticles and platelet
      surface P-selectin expression after coronary stent implantation.
AB  - Platelet-derived microparticles (PDMPs) are released from activated platelets and
      may participate in the inflammatory process in response to vessel wall injury.
      This study was designed to compare the clinical significance of circulating PDMPs
      with that of P-selectin on the platelet membrane surface. In 20 patients with
      stable angina undergoing coronary stent implantation, circulating PDMPs were
      serially measured by enzyme-linked immunosorbent assay, and P-selectin expression
      on the surface of platelets was simultaneously analyzed by flow cytometry. PDMPs
      increased 24-48 h after coronary stenting in the coronary sinus (8.7 +/- 8.9 to
      31.8 +/- 19.8 U/ml, P < 0.001) with a maximum at 48 h. In contrast, the mean
      channel fluorescence intensity for P-selectin increased 15 min after coronary
      stenting in the coronary sinus (19.5 +/- 5.6 to 25.2 +/- 7.5, P < 0.01) and
      remained elevated for 48 h; the changes were less striking in peripheral blood.
      The relative increase in PDMPs was not correlated with the increase in P-selectin
      expression at 15 min or 24 h after coronary stenting, but was correlated at 48 h
      (R = 0.48, P < 0.05). Both circulating PDMPs and P-selectin expression were
      enhanced in association with stent-induced platelet activation; however, the time
      course of changes in these two platelet activation markers was different.
      Therefore, the clinical relevance of circulating PDMPs may differ from that of P
      selectin expression on the platelet membrane surface.

PMID- 16973504
TI  - Human platelet Ca2+-ATPases: new markers of cell differentiation as illustrated
      in idiopathic scoliosis.
AB  - The aetiology of adolescent idiopathic scoliosis (AIS), the most common form of
      scoliosis, is unclear. Previous studies showed controversial platelet
      abnormalities including intracellular calcium. Platelet Ca2+ homeostasis is
      controlled by a multi-Ca2+-ATPase system including SERCA (sarco/endoplasmic
      reticulum Ca2+-ATPase) and PMCA (plasma membrane Ca2+-ATPase) isoforms. Here, we
      first investigated the expression of PMCA4b, SERCA3a and SERCA2b isoforms in
      platelets of 17 patients with AIS. Patients presenting thoracic curves were found
      to present a higher PMCA4b expression coupled to a lower SERCA3a one in agreement
      with an abnormality in platelet maturation. Indeed, using PMA-treated MEG 01
      cells, an in vitro model of megakaryocytopoiesis, we found an increase in SERCA3a
      expression, associated to a caspase-3 mediated C terminal proteolysis of PMCA4b.
      To look whether platelets reflect a basic defect in cell differentiation, we next
      identified osteoblast Ca2+-ATPases and studied their expressions in AIS. Major
      expressions of PMCA4b and SERCA2b were found in normal osteoblasts. Comparing
      platelets and osteoblasts in two additional patients with AIS, we found opposite
      and concerted regulations of the expressions of PMCA4b and caspase-3 substrate,
      PARP in both cell types. A systemic defect in cell differentiation involving
      caspase-3 can be proposed as a novel mechanism in the etiopathogenesis of the
      most frequent type of AIS. *R. Bredoux and E. Corvazier contributed equally to
      this work.

PMID- 16973505
TI  - Guideline on targets for solute and fluid removal in adult patients on chronic
      peritoneal dialysis.

PMID- 16973506
TI  - Statins for treatment of dyslipidemia in chronic kidney disease.
AB  - Dyslipidemia is a potent cardiovascular (CV) risk factor in the general
      population. Elevated low-density lipoprotein cholesterol (LDL-C) and/or low high
      density lipoprotein (HDL-C) are well-established CV risk factors, but more
      precise determinants of risk include increased apoprotein B (ApoB),
      lipoprotein(a) [Lp(a)], intermediate and very low-density lipoprotein (IDL-C,
      VLDL-C; "remnant particles"), and small dense LDL particles. Lipoprotein
      metabolism is altered in association with declining glomerular filtration rate
      such that patients with non dialysis-dependent chronic kidney disease (CKD) have
      lower levels of HDL-C, higher triglyceride, ApoB, remnant IDL-C, remnant VLDL-C,
      and Lp(a), and a greater proportion of oxidized LDL-C. Similar abnormalities are
      prevalent in hemodialysis (HD) patients, who often manifest proatherogenic
      changes in LDL-C in the absence of increased levels. Patients treated with
      peritoneal dialysis (PD) have a similar but more severe dyslipidemia compared to
      HD patients due to stimulation of hepatic lipoprotein synthesis by glucose
      absorption from dialysate, increased insulin levels, and selective protein loss
      in the dialysate analogous to the nephrotic syndrome. In the dialysis-dependent
      CKD population, total cholesterol is directly associated with increased mortality
      after controlling for the presence of malnutrition-inflammation. Treatment with
      statins reduces CV mortality in the general population by approximately one
      third, irrespective of baseline LDL-C or prior CV events. Statins have similar,
      if not greater, efficacy in altering the lipid profile in patients with dialysis
      dependent CKD (HD and PD) compared to those with normal renal function, and are
      well tolerated in CKD patients at moderate doses (<or=20 mg/day atorvastatin or
      simvastatin). Statins reduce C-reactive protein as well as lipid moieties such as
      ApoB, remnants IDL and VLDL-C, and oxidized and small dense LDL-C fraction. Large
      observational studies demonstrate that statin treatment is independently
      associated with a 30%-50% mortality reduction in patients with dialysis-dependent
      CKD (similar between HD- and PD-treated patients). One recent randomized
      controlled trial evaluated the ability of statin treatment to reduce mortality in
      type II diabetics treated with HD ("4D"); the primary end point of death from
      cardiac cause, myocardial infarction, and stroke was not significantly reduced.
      However, results of this trial may not apply to other end-stage renal disease
      populations. Two ongoing randomized controlled trials (SHARP and AURORA) are
      underway evaluating the effect of statins on CV events and death in patients with
      CKD (including patients treated with HD and PD). Recruitment to future trials
      should be given a high priority by nephrologists and, until more data are
      available, consideration should be given to following published guidelines for
      the treatment of dyslipidemia in CKD. Additional consideration could be given to
      treating all dialysis patients felt to be at risk of CV disease (irrespective of
      cholesterol level), given the safety and potential efficacy of statins. This is
      especially relevant in patients treated with PD, given their more atherogenic
      lipid profile and the lack of randomized controlled trials in this population.

PMID- 16973507
TI  - Peritoneal dialysis international: its past, present, and future.

PMID- 16973508
TI  - Adenovirus-based transient expression systems for peritoneal membrane research.
AB  - BACKGROUND: Peritoneal membrane research has provided important insights into the
      physiology and pathophysiology of this tissue that is of vital importance for
      peritoneal dialysis patients. Among the various tools and methodologies used to
      study the peritoneum, we have extensively used adenovirus-mediated gene transfer.
      METHODS: A literature review was carried out. Information from reviewed papers
      was combined with the authors' experience and results. RESULTS: We have used
      first-generation adenoviruses that are simple to construct and can infect a wide
      range of dividing and nondividing cell types. These vectors are restricted,
      however, in that they provide only a short duration of transgene expression and
      may elicit an inflammatory response. Modifications to this technology with helper
      dependent adenovirus may circumvent these problems but with increased complexity
      of construction. Adenovirus-mediated gene transfer has been used to evaluate the
      effect of several cytokines and growth factors on peritoneal membrane physiology.
      We have used intraperitoneal delivery of transforming growth factor-beta to
      generate an experimental model system of resolving peritoneal fibrosis and
      epithelial mesenchymal transdifferentiation. We have studied the effects of the
      inflammatory cytokines interleukin-1beta and tumor necrosis factor alpha on the
      peritoneum, and have shown that antiangiogenic factors such as sFLT-1 and
      angiostatin can reduce the damaging effects of exposure to peritoneal dialysis
      solutions in an animal model. CONCLUSIONS: The use of recombinant adenoviruses to
      genetically modify cells and tissues is now a common laboratory research tool.
      This technique has provided important advances in our understanding of the
      peritoneal membrane.

PMID- 16973509
TI  - An international encapsulating peritoneal sclerosis registry and DNA bank: why we
      need one now.

PMID- 16973510
TI  - Encapsulating peritoneal sclerosis: time to act.

PMID- 16973511
TI  - Extracellular water expansion: part of the malnutrition-inflammation
      atherosclerosis syndrome?

PMID- 16973512
TI  - Animal models in peritoneal dialysis: a story of kangaroos and ostriches.

PMID- 16973513
TI  - Inflammation and extracellular volume expansion are related to sodium and water
      removal in patients on peritoneal dialysis.
AB  - BACKGROUND: Inflammation is an important risk for mortality in dialysis patients.
      Extracellular fluid volume (ECFv) expansion, a condition commonly seen in
      peritoneal dialysis (PD) patients, may be associated with inflammation. However,
      published support for this relationship is scarce. OBJECTIVES: To quantify the
      proportion of patients on PD with inflammation and to analyze the role of ECFv
      expansion and the factors related to these conditions. DESIGN: A prospective,
      multicenter cross-sectional study in six hospitals with a PD program. PATIENTS
      AND METHODS: Adult patients on PD were studied. Clinical data, body composition,
      and sodium and fluid intake were recorded. Biochemical analysis, C-reactive
      protein (CRP), and peritoneal and urinary fluid and sodium removal were also
      measured. RESULTS: CRP values positive (>or=3.0 mg/L) for inflammation were found
      in 147 (80.3%) and negative in 36 patients. Patients with positive CRP had higher
      ECFv/total body water (TBW) ratio (women 47.69 +/- 0.69 vs 47.36 +/- 0.65, men
      43.15 +/- 1.14 vs 42.84 +/- 0.65; p < 0.05), higher serum glucose (125.09 +/-
      81.90 vs 103.28 +/- 43.30 mg/dL, p < 0.03), and lower serum albumin (2.86 +/-
      0.54 vs 3.17 +/- 0.38 g/dL, p < 0.001) levels. They also had lower
      ultrafiltration (1003 +/- 645 vs 1323 +/- 413 mL/day, p < 0.005) and total fluid
      removal (1260 +/- 648 vs 1648 +/- 496 mL/day, p < 0.001), and less peritoneal
      (15.59 +/- 162.14 vs 78.11 +/- 110.70 mEq/day, p < 0.01) and total sodium removal
      (42.06 +/- 142.49 vs 118.60 +/- 69.73 mEq/day, p < 0.001). In the multivariate
      analysis, only ECFv/TBW was significantly (p < 0.04) and independently associated
      with inflammation. ECFv/TBW was correlated with fluid removal (r = 0.16, p <
      0.03) and renal sodium removal (r = 0.2, p < 0.01). CONCLUSION: The data suggest
      that ECFv expansion may have a significant role as an inflammatory stimulus. The
      results disclose a relationship between the two variables, ECFv expansion and
      inflammation, identified as independent risk factors for mortality in PD
      patients.

PMID- 16973514
TI  - Correlation between fractional reabsorption of sodium and erythropoietin dose in
      peritoneal dialysis patients.
AB  - BACKGROUND: Erythropoietin (EPO) deficiency of chronic renal failure (CRF) may be
      a functional consequence of decreased glomerular filtration rate and fractional
      reabsorption of sodium (FR(Na)). Decreased FR(Na) reduces renal oxygen
      consumption and increases tissue oxygen pressure, resulting in less EPO
      production. We hypothesized that, in CRF patients, there is a positive
      relationship between EPO production and FR(Na) and that, in such patients
      receiving EPO, a negative correlation is expected between FR(Na) and EPO dose.
      METHODS: Creatinine clearance, FR(Na), serum iron, transferrin, transferrin
      saturation, ferritin, and intact parathyroid hormone (iPTH) levels were measured
      in 91 peritoneal dialysis patients. The correlation between EPO dose and FR(Na)
      was studied. RESULTS: Mean EPO dose was 7076 +/- 4821 units/week and mean FR(Na)
      was 93.40% +/- 6.14%. A negative correlation was found between EPO dose and
      FR(Na) (r = -0.28, p < 0.01), and a positive correlation was found between both
      ferritin and iPTH and EPO dose (r = 0.39, p < 0.001 and r = 0.35, p < 0.002
      respectively). After adjusting for the effect of creatinine clearance, ferritin,
      and iPTH, there was still a significant correlation between EPO dose and FR(Na)
      (p < 0.05). CONCLUSION: In CRF patients there is a negative correlation between
      FR(Na) and EPO dose, which supports the hypothesis that EPO deficiency may be
      related to the decreased renal oxygen-consuming work of sodium reabsorption.

PMID- 16973515
TI  - No significant differences in peritoneal fluid handling in children using PH
      neutral or acidic solutions.
AB  - OBJECTIVES: Differences in peritoneal fluid handling in the acute setting can be
      expected if children are converted to pH-neutral dialysis solutions because
      conventional acidic solutions exert toxic effects on peritoneal mesothelial cells
      and microcirculation. Peritoneal fluid kinetics was therefore investigated with
      both types of solutions in a group of children. DESIGN: Peritoneal equilibration
      tests (PETs) were performed in 12 patients [mean age 70 months, mean time on
      peritoneal dialysis (PD) 18 months] using a pH-neutral PD fluid (Physioneal
      3.86%; Baxter Ltd, Castlebar, Ireland) and dextran 70 as a volume marker. The
      results of these PETs were compared to those of a historic group of 12 children
      (mean age 75 months, mean time on PD 17 months). SETTING: Pediatric dialysis unit
      in a tertiary institute. PATIENTS: Stable pediatric PD patients. MAIN OUTCOME
      MEASURES: Transcapillary ultrafiltration (TCUF) and marker clearance, dialysate
      to-plasma (D/P) ratios for urea and creatinine, and D(t)/D(0) ratio for glucose.
      RESULTS: TCUF and lymphatic absorption were not different between the two groups.
      There was also no significant difference in small solute clearance measured by
      D/P ratio for urea and creatinine and D(t)/D(0) ratio for glucose. CONCLUSION:
      Peritoneal fluid kinetics is not significantly altered if pH-neutral dialysis
      solutions are applied compared to acidic solutions. An altered TCUF, as is
      hypothetically possible using an acidic solution, was not established.

PMID- 16973516
TI  - Stability of cefazolin sodium in four heparinized and non-heparinized dialysate
      solutions at 38 degrees C.
AB  - BACKGROUND: Intraperitoneal administration of antibiotics is often required in
      the treatment of peritoneal dialysis-associated peritonitis. Extended use and
      heating may affect drug stability. The objective of our study was to determine
      the stability of cefazolin sodium (125 mg/L and 500 mg/L) in heparinized and non
      heparinized dextrosecontaining peritoneal dialysis solution (Dianeal PD-2; Baxter
      Healthcare, Deerfield, Illinois, USA) containing 1.5%, 2.5%, or 4.25% dextrose,
      or 7.5% icodextrin, the new colloid formulation (Extraneal; Baxter), at 38
      degrees C for 4 days. METHODS: Three poly-vinyl chloride containers of each
      dialysis fluid were stored at 38 degrees C for 4 days. Samples were taken after
      the bags were mixed and allowed to stand for 2 minutes. Two 500-microL samples
      were collected from each bag at hours 0, 12, 24, 36, 48, 60, 72, 84, and 96.
      Samples were then analyzed by high-performance liquid chromatography (HPLC) in
      our laboratory. In order to establish the stability-indicating nature of the
      method, drugs 1.0 mg/mL, vehicles, and their mixtures were subjected to a forced
      degradation. This is done by acid (2.0 mol/L HCl) and base (2.0 mol/L NaOH)
      hydrolysis, oxidation (H(2)O(2) 0.3%), and heat at 80 degrees C. Samples were
      analyzed every 30 minutes until approximately 25% of the drug's peak disappeared.
      The drug was considered stable if its concentration exceeded 90% of the original.
      RESULTS: For all Dianeal PD-2 peritoneal dialysis solution containing 1.5%, 2.5%,
      and 4.25% dextrose, cefazolin sodium was considered stable at 38 degrees C for 60
      hours at low cefazolin concentrations (125 mg/L), both with and without heparin,
      and for 48 hours at high cefazolin concentrations (500 mg/L). Cefazolin sodium
      was considered stable at 38 degrees C in icodextrin for 48 hours at low cefazolin
      concentrations in heparinized and non-heparinized solutions, and at high
      concentrations only in non-heparinized dialysate, not in heparinized dialysate.
      Cefazolin sodium was considered stable at 38 degrees C in icodextrin for 60 hours
      at high concentrations when heparinized. CONCLUSION: Cefazolin sodium was stable
      in all four nonheparinized dialysate fluids for at least 48 hours at 38 degrees
      C. In heparinized icodextrin dialysate, high concentrations of cefazolin sodium
      were not stable for extended periods of time. Extended use and heating of
      dialysate containing cefazolin may adversely affect patient outcome.

PMID- 16973517
TI  - CAPD in sheep following bilateral nephrectomy.

PMID- 16973518
TI  - B-type natriuretic peptide and amino-terminal atrial natriuretic peptide predict
      survival in peritoneal dialysis.

PMID- 16973519
TI  - Characteristics of patients continually undergoing peritoneal dialysis for over
      ten years in Japan.

PMID- 16973520
TI  - Icodextrin increases natriuretic peptides in diabetic patients undergoing CAPD.

PMID- 16973521
TI  - Gram-negative and polymicrobial peritonitis are associated with subsequent fungal
      peritonitis in CAPD patients.

PMID- 16973522
TI  - Extensive peritoneal calcification as a complication of long-term peritoneal
      dialysis and secondary hyperparathyroidism: a case report and review of the
      literature.

PMID- 16973523
TI  - Relapsing Bacillus cereus peritonitis during automated peritoneal dialysis.

PMID- 16973524
TI  - Hope, ethics, and public health.

PMID- 16973525
TI  - Implications for health in a low carbon (Contract and Converge) world.

PMID- 16973526
TI  - Waterborne diseases prevention: evaluation of inspection scoring system for water
      sites according to water microbiological tests during the Athens 2004 pre-Olympic
      and Olympic period.
AB  - STUDY OBJECTIVES: To evaluate the inspection grading system for water sites
      implemented during the Athens 2004 Olympic inspection programme. DESIGN: The
      relation between the standardised inspections results of 716 water supply systems
      and 289 public swimming pools, and microbiological test results of 2358 samples
      collected during inspections was examined. SETTING: Athens, Thessaloniki, Patra,
      Volos, and Iraklio, Greece. Inspections and sampling conducted during a two year
      period before the 2004 Olympics. MAIN RESULTS: Swimming pools unsatisfactory
      inspection grading results were significantly associated with positive water
      microbiological test results (relative risk = 2.5, p<0.05). One of the six
      violations of swimming pools and five of the seven violations of water supply
      systems designated as "critical" water safety hazards in the inspection reports
      were significantly associated with positive microbiological test results. The
      receiver operating characteristic analysis identified the unsatisfactory score
      designed in the swimming pools standardised inspection report, as the ideal score
      (-15), in adequately producing positive microbiological test results (sensitivity
      13.2%, specificity 89%). CONCLUSIONS: This study shows the utility of
      standardised inspection grading systems in waterborne diseases prevention
      planning and implementation strategies of policy makers and regulators. Future
      water quality assessment should be based on the implementation of a robust
      standardised inspection system and reduce the need of microbiological tests.

PMID- 16973527
TI  - Treatment and care of HIV positive asylum seekers.
AB  - BACKGROUND: Enhanced regional surveillance in north west England suggests that
      the proportion of HIV positive people who are asylum seekers (AS) is increasing.
      Nationally, there is no empirical evidence that HIV positive AS use HIV services
      to a greater or lesser extent than HIV positive non-AS. This report compares
      stage of disease and use of services between HIV positive non-AS and AS. METHODS:
      Data on those accessing HIV treatment and care (from hospitals and non
      governmental organisations (NGOs)) in the north west of England for the first
      time January 2001-June 2004 (total 2204; AS 409) were extracted from the regional
      enhanced surveillance system. RESULTS: Compared with non-AS, AS did not differ in
      stage of HIV disease on first contact (p>0.05), were no more likely to stay
      overnight in hospital (p>0.05), but had an average of one extra outpatient
      appointment per year (median seven compared with six, p = 0.014). AS were much
      more likely to have accessed NGOs for support (43% compared with 27%: p<0.001).
      CONCLUSIONS: Use of specialist hospital services by HIV positive AS differs
      little from HIV positive persons who are not AS. However, HIV positive AS rely
      more on NGOs at a time when such voluntary services are under increasing
      financial pressures.

PMID- 16973529
TI  - Methodology for optimising location of new primary health care facilities in
      rural communities: a case study in KwaZulu-Natal, South Africa.
AB  - STUDY OBJECTIVE: To develop a quantitative methodology to optimally site new
      primary health care facilities so as to achieve the maximum population level
      increase in accessibility to care. The study aims to test the methodology in a
      rural community characterised by considerable heterogeneity in population
      distribution and health care access. DESIGN: A geographical information system
      was used to estimate travel time to the nearest primary health care facility for
      each of the 26 000 homesteads in the subdistrict. The homestead's travel time
      estimate was then converted into an impedance to care estimate using distance
      decay (in clinic use) data obtained from the subdistrict. A map of total person
      impedance/km(2) was then produced using a 3 km standard Gaussian filter. The
      resulting map was used to site a test clinic in the largest contiguous area of
      high person impedance. SETTING: Hlabisa health subdistrict, KwaZulu-Natal, South
      Africa. MAIN RESULTS: The population level increase in accessibility that would
      be achieved by the construction of the test clinic would be 3.6 times the
      increase in accessibility achieved by the construction of the newest clinic in
      the subdistrict. The corresponding ratio for increasing clinic coverage (% of the
      population within 60 minutes of care) would be 4.7. CONCLUSIONS: The methodology
      successfully identifies a locality for a new facility that would maximise the
      population level increase in accessibility to care. The same principles used in
      this research could also be applied in other settings. The methodology is of
      practical value in health research and practice and provides a framework for
      optimising location of new primary health care facilities.

PMID- 16973528
TI  - Effectiveness calculation in economic analysis: the case of statins for
      cardiovascular disease prevention.
AB  - OBJECTIVES: This report aimed to evaluate the calculation of estimates of
      effectiveness in cost effectiveness analyses of statins for cardiovascular
      disease prevention. METHODS: Methodological aspects were reviewed of seven
      primary studies (based on trial results) and 12 secondary modelling studies
      (extrapolated) on the cost effectiveness of statin treatment, published between
      1995 and 2002. Estimates of life years gained were extracted and compared with
      estimates calculated using the Dutch male life table of 1996-2000. RESULTS: Of
      the seven primary modelling analyses, six showed all the essential data. They
      estimated that 3 to 5.6 years (average 4.6 years) of statin treatment resulted in
      0.15 to 0.41 years (average 0.3 years) saved over a lifetime time horizon. In
      contrast none of the 12 secondary modelling studies provided transparent results.
      They assumed lifelong treatment, leading to life table estimations of 2.4 and 2.0
      (undiscounted) years saved for 40 and 60 year olds, with peak savings at around
      the mean age of death: 75-80 years. With 5% discounting, these effects reduced to
      0.4 and 0.8 years respectively. CONCLUSION: Reporting of essential data and
      assumptions on statin treatment was poor for secondary modelling analyses and
      satisfactory for primary modelling studies. Secondary modeling studies made
      assumptions on long term effectiveness that were hard to justify with the
      available evidence, and that led to the majority of life years saved at high
      ages. Further standardisation in economic analyses is important to guarantee
      transparency and reproducibility of results.

PMID- 16973530
TI  - Advanced paternal age: how old is too old?
AB  - Average paternal age in the UK is increasing. The public health implications of
      this trend have not been widely anticipated or debated. This commentary aims to
      contribute to such a debate. Accumulated chromosomal aberrations and mutations
      occurring during the maturation of male germ cells are thought to be responsible
      for the increased risk of certain conditions with older fathers. Growing evidence
      shows that the offspring of older fathers have reduced fertility and an increased
      risk of birth defects, some cancers, and schizophrenia. Adverse health outcomes
      should be weighed up against advantages for children born to older parents,
      mindful that these societal advantages are likely to change over time.

PMID- 16973531
TI  - Participatory action research.
AB  - This glossary aims to clarify some of the key concepts associated with
      participatory action research.

PMID- 16973532
TI  - Pragmatic randomised controlled trials in parenting research: the issue of
      intention to treat.
AB  - STUDY OBJECTIVE: To evaluate trials of parenting programmes, regarding their use
      of intention to treat (ITT). DESIGN: Individual trials included in two relevant
      Cochrane systematic reviews were scrutinised by two independent reviewers. Data
      on country of origin, target audience, trial type, treatment violations, use of
      ITT, and the management of missing data were extracted. MAIN RESULTS: Thirty
      trial reports were reviewed. Three reported the use of an ITT approach to data
      analysis. Nineteen reported losing subjects to follow up although the
      implications of this were rarely considered. Insufficient detail in reports meant
      it was difficult to identify study drop outs, the nature of treatment violations,
      and those failing to provide outcome assessments. In two trials, study drop outs
      were considered as additional control groups, violating the basic principle of
      ITT. CONCLUSIONS: It is recommended that future trial reports adhere to CONSORT
      guidelines. In particular ITT should be used for the main analyses, with
      strategies for managing treatment violations and handling missing data being
      reported a priori. Those conducting trials need to acknowledge the social nature
      of these programmes can sometimes result in erratic parent attendance and
      participation, which would only increase the chances of missing data. The use of
      approaches that can limit the proportion of missing data is therefore
      recommended.

PMID- 16973533
TI  - Maternal social capital and child health in Vietnam.
AB  - STUDY OBJECTIVE: To explore the association between maternal social capital and
      child physical and mental health in Vietnam. DESIGN: Cross sectional survey.
      Measures of maternal structural social capital comprised group membership,
      citizenship, and social support. Measures of cognitive social capital comprised
      trust, social harmony, sense of fairness, and belonging. Child health was
      measured by anthropometrics and mothers' reports of acute and chronic physical
      health problems and child mental health. PARTICIPANTS: 2907 mothers and their 1
      year old or 8 year old children from five provinces in Vietnam. MAIN RESULTS: The
      study found low levels of group membership and citizenship and high levels of
      cognitive social capital and support, and generally higher levels of social
      capital among the mothers of 8 year old compared with 1 year old children. All
      but one association was in the hypothesised direction (that is, higher levels of
      social capital associated with reduced risk of child health problems). There were
      more statistically significant relations between maternal social capital and the
      health of 1 year olds compared with 8 year old children, and between measures of
      social support and cognitive social capital and child health, than with group
      membership and involvement in citizenship activities. CONCLUSION: This study is
      the first to explore the association between multiple dimensions of social
      capital and a range of different child health outcomes in the developing world.
      These results now need to be tested using longitudinal data.

PMID- 16973534
TI  - Childhood IQ and life course socioeconomic position in relation to alcohol
      induced hangovers in adulthood: the Aberdeen children of the 1950s study.
AB  - OBJECTIVE: To examine the association between scores on IQ tests in childhood and
      alcohol induced hangovers in middle aged men and women. DESIGN, SETTING, AND
      PARTICIPANTS: A cohort of 12 150 people born in Aberdeen (Scotland) who took part
      in a school based survey in 1962 when IQ test scores were extracted from
      educational records. Between 2000 and 2003, 7184 (64%) responded to questionnaire
      inquiries regarding drinking behaviour. MAIN OUTCOME MEASURES: Self reported
      hangovers attributable to alcohol consumption on two or more occasions per month.
      RESULTS: Higher IQ scores at 11 years of age were associated with a lower
      prevalence of hangovers in middle age (OR(per one SD advantage in IQ score); 95%
      CI: 0.80; 0.72, 0.89). This relation was little affected by adjustment for
      childhood indicators of socioeconomic position (0.82; 0.74, 0.91) but was
      considerably attenuated after control for adult variables (fully adjusted model:
      0.89; 0.79, 1.01). CONCLUSIONS: Higher childhood IQ was related to a lower
      prevalence of alcohol induced hangovers in middle aged men and women. The IQ
      hangover effect may at least partially explain the link between early life IQ and
      adult mortality. This being the first study to examine this relation, more
      evidence is required.

PMID- 16973535
TI  - The changing relation between education and life expectancy in central and
      eastern Europe in the 1990s.
AB  - BACKGROUND: The political and social transition in central and eastern Europe has
      been generally associated with widening educational differences in life
      expectancy. However, interpretation of these findings is complicated because the
      size of educational categories within the population has also changed. It is
      therefore important to disentangle these two phenomena. SETTING: The Czech
      Republic, Estonia, the Russian Federation and, as a western European reference,
      Finland, in two periods, 1988-89 and 1998-99. METHODS: Life tables were
      calculated in three categories: university; secondary; and less than secondary
      education. Changes in life expectancy were decomposed into contributions of
      population composition and within-category mortality. RESULTS: In Finland and the
      Czech Republic improvements are seen in all educational groups, with only a
      slight widening of the educational differences. Over 80% of the total life
      expectancy increase is attributable to improved mortality within educational
      categories. In Estonia and Russia, less favourable overall trends coincide with a
      dramatic widening of the educational gap. A decrease in life expectancy in those
      with low and middle education has been compensated for, to a small degree in
      Russia but a greater extent in Estonia, by improvements among those with higher
      education and by the improved population composition. For highly educated
      Estonians, the gains were seen at all ages, the greatest at age > or =60 years.
      In Russia mortality increased in those <60 years although compensated for by
      improvements at older ages. CONCLUSIONS: Russia and Estonia exhibit much less
      equitable transitions compared with the Czech Republic. Analyses of trends in
      health inequalities should capture the changing population composition. In Russia
      and Estonia an improved educational structure prevented an even greater decline
      in life expectancy. The highly educated Estonians can potentially catalyse a
      wider health progress.

PMID- 16973536
TI  - Comparison of the effects of low childhood socioeconomic position and low
      adulthood socioeconomic position on self rated health in four European studies.
AB  - BACKGROUND: Socioeconomic inequalities in health are a persistent feature
      throughout Europe. Researchers and policy makers are increasingly using a
      lifecourse perspective to explain these inequalities and direct policy. However,
      there are few, if any, cross national lifecourse comparisons in this area.
      METHODS: Associations between socioeconomic position (SEP) in childhood and in
      adulthood and poor self rated health among men and women at midlife were tested
      in four European studies from England (n = 3615), France (n = 11 595), Germany (n
      = 4183), and the Netherlands (n = 3801). RESULTS: For women, mutually adjusted
      analyses showed significant associations between poor self rated health and low
      SEP in both childhood and adulthood in England and the Netherlands, only low
      childhood SEP in Germany and neither childhood nor adulthood SEP in France. For
      men, mutually adjusted analyses showed significant associations between poor self
      rated health and low SEP in both childhood and adulthood in France and the
      Netherlands, only with adult SEP in England and only with childhood SEP in
      Germany. CONCLUSION: In most countries adult SEP showed stronger associations
      with self rated health than childhood SEP. There are both gender and national
      differences in the associations between childhood and adulthood SEP. Policies
      designed to reduce inequalities in health need to incorporate a lifecourse
      perspective that is sensitive to different national and gender issues.
      Ultimately, more cross national studies are required to better understand these
      processes.

PMID- 16973537
TI  - Epidemiological disaster research: the necessity to include representative
      samples of the involved disaster workers. Experience from the epidemiological
      study air disaster Amsterdam-ESADA.
AB  - OBJECTIVE: To study whether the methods used to select participants in research
      on prevalence rates of the health effects of exposure to a disaster may cause
      bias. This study compared background characteristics, disaster exposure, and
      complaints reported by (1) police officers who participated in an epidemiological
      study and underwent a medical examination, and (2) police officers who only
      participated in an epidemiological study. DESIGN AND SETTING: In 2000, an
      epidemiological study was started to investigate the health status among police
      officers who were involved in assistance work related to the air disaster in
      Amsterdam: the epidemiological study air disaster Amsterdam (ESADA). These police
      officers were personally invited to participate in the epidemiological study and
      were additionally offered a medical examination, providing them with the
      opportunity to have their health checked by a medical doctor. PARTICIPANTS: Of
      the total group of involved police officers who were invited, 834 (70%)
      participated in the ESADA: 224 (26.9%) only participated in the study, but 610
      (73.1%) also underwent the medical examination. MAIN RESULTS: Police officers who
      underwent a medical examination significantly more often reported one or more
      musculoskeletal complaints, skin complaints, general or non-specific complaints,
      had more often experienced an event with potentially traumatic impact, or had
      performed one or more potentially traumatic tasks. CONCLUSIONS: The methods of
      selection of participants are important in research on health effects after
      disasters and can result in an overestimation of some of the effects, on average,
      by a factor of 1.5 to 2.

PMID- 16973538
TI  - Air pollution and emergency admissions in Boston, MA.
AB  - STUDY OBJECTIVE: Many studies have shown that ambient particulate air pollution
      (PM) is associated with increased risk of hospital admissions and deaths for
      cardiovascular or respiratory causes around the world. In general these have been
      analysed in association with PM(10) and ozone, whereas PM(2.5) is now the
      particle measure of greatest health and regulatory concern. And little has been
      published on associations of hospital admissions and PM components. DESIGN: This
      study analysed hospital admissions for myocardial infarction (15 578 patients),
      and pneumonia (24 857 patients) in associations with fine particulate air
      pollution, black carbon (BC), ozone, nitrogen dioxide (NO(2)), PM not from
      traffic, and carbon monoxide (CO) in the greater Boston area for the years 1995
      1999 using a case-crossover analysis, with control days matched on temperature.
      MAIN RESULTS: A significant association was found between NO(2) (12.7% change
      (95% CI: 5.8, 18)), PM(2.5) (8.6% increase (95% CI: 1.2, 15.4)), and BC (8.3%
      increase (95% CI: 0.2, 15.8)) and the risk of emergency myocardial infarction
      hospitalisation; and between BC (11.7% increase (95% CI: 4.8, 17.4)), PM(2.5)
      (6.5% increase (95% CI: 1.1, 11.4)), and CO (5.5% increase (95% CI: 1.1, 9.5))
      and the risk of pneumonia hospitalisation. CONCLUSIONS: The pattern of
      associations seen for myocardial infarction and pneumonia (strongest associations
      with NO(2), CO, and BC) suggests that traffic exposure is primarily responsible
      for the association with heart attacks.

PMID- 16973539
TI  - Social determinants of health: a veil that hides socioeconomic position and its
      relation with health.
AB  - The emergence of theoretical models of social determinants of health has added
      conceptual ambiguity to the understanding of social inequalities in health, as it
      is often not possible to clearly distinguish between socioeconomic position and
      these determinants. Whether the existence of social inequalities in health is
      based on differences in health or on differences in social determinants of health
      that are systematically associated with socioeconomic position, policymakers
      should be clearly informed of the importance of socioeconomic position for
      health. Thus, the following three basic requirements are proposed: to reach a
      consensus about the dimensions that reflect socioeconomic position; to agree
      about what are to be considered the social determinants of health and whether or
      not these determinants are a construct that can be distinguished from
      socioeconomic position; and finally, to establish which dimensions and measures
      of socioeconomic position are most appropriate for the evaluation of
      interventions that aim to reduce these inequalities.

PMID- 16973540
TI  - A model for collaborative evaluation of university-community partnerships.
AB  - INTRODUCTION: Manitoba's The Need to Know project was presented with a unique
      opportunity to develop a collaborative approach to evaluation, and to explore the
      effectiveness of a variety of evaluation methods for assessment of university
      community collaborative health research partnerships. OBJECTIVES: The evaluation
      was designed to incorporate participation of community partners in planning,
      developing, and evaluating all aspects of the project. Objectives included: (a)
      assessment of extent to which the project met its initial objectives; (b)
      assessment of extent participants needs and expectations were met; (c) refinement
      of evaluation questions; (d) identification of unanticipated impacts; (e)
      assessment of participant confidence as research team members; (f) development of
      knowledge translation theory; and (g) component analysis. METHODS: A "utilisation
      focused" approach was used. Primary stakeholders identified evaluation questions
      of concern, and how findings would be used. The multimethod time series design
      incorporated key informant interviews, a pre/post-test survey, written workshop
      evaluations, and participant and unobtrusive observation. All aspects of the
      evaluation were made transparent to participants, and formal feedback processes
      were instituted. RESULTS: There was a high level of participation in evaluation
      activities. Identifying evaluation questions of concern to community partners
      helped shape project development. While all methods provided useful information,
      only key informant interviews, participant observation and feedback processes
      provided insights into all evaluation objectives. CONCLUSION: Collaborative
      evaluation can make an important contribution to development of university
      community partnerships. Qualitative methods (particularly key informant
      interviews, participant observation, and feedback processes) provided the richest
      source of data, and made an important contribution to team development.

PMID- 16973542
TI  - Canine distemper virus uses both the anterograde and the hematogenous pathway for
      neuroinvasion.
AB  - Canine distemper virus (CDV), a member of the Morbillivirus genus that also
      includes measles virus, frequently causes neurologic complications, but the
      routes and timing of CDV invasion of the central nervous system (CNS) are poorly
      understood. To characterize these events, we cloned and sequenced the genome of a
      neurovirulent CDV (strain A75/17) and produced an infectious cDNA that expresses
      the green fluorescent protein. This virus fully retained its virulence in
      ferrets: the course and signs of disease were equivalent to those of the parental
      isolate. We observed CNS invasion through two distinct pathways: anterogradely
      via the olfactory nerve and hematogenously through the choroid plexus and
      cerebral blood vessels. CNS invasion only occurred after massive infection of the
      lymphatic system and spread to the epithelial cells throughout the body. While at
      early time points, mostly immune and endothelial cells were infected, the virus
      later spread to glial cells and neurons. Together, the results suggest
      similarities in the timing, target cells, and CNS invasion routes of CDV, members
      of the Morbillivirus genus, and even other neurovirulent paramyxoviruses like
      Nipah and mumps viruses.

PMID- 16973541
TI  - Pathogenesis of West Nile Virus infection: a balance between virulence, innate
      and adaptive immunity, and viral evasion.

PMID- 16973543
TI  - Optimization of feline immunodeficiency virus vectors for RNA interference.
AB  - RNA interference (RNAi) occurs naturally in plant and animal cells as a means for
      modulating gene expression. This process has been experimentally manipulated to
      achieve targeted gene silencing in cells, tissues, and animals, using a variety
      of vector systems. Here, we tested the hypothesis that vectors based on feline
      immunodeficiency virus (FIV) could be used for coexpression of reporter
      constructs and RNAi expression cassettes. We found, unexpectedly, in our initial
      constructs that placement of RNAi expression cassettes downstream from a
      polymerase II (pol II)-expressed reporter gene inhibited reporter expression but
      not vector titer. Through a series of intermediate vector constructs, we found
      that placement of the RNAi expression cassette relative to the Rev response
      element and the pol II expression cassette was critical for efficient RNAi and
      reporter gene expression. These results suggested that steric factors, including
      RNA structure and recruitment of competing transcriptional machinery, may affect
      gene expression from FIV vectors. In a second series of studies, we show that
      target sequence silencing can be achieved in cells transduced by FIV vectors
      coexpressing reporter genes and 3' untranslated region resident microRNAs. The
      optimized FIV-based RNAi expression vectors will find broad use given the
      extensive tropism of pseudotyped FIV vectors for many cell types in vitro and in
      vivo.

PMID- 16973544
TI  - ICP22 is required for wild-type composition and infectivity of herpes simplex
      virus type 1 virions.
AB  - The immediate-early regulatory protein ICP22 is required for efficient
      replication of herpes simplex virus type 1 in some cell types (permissive) but
      not in others (restrictive). In mice infected via the ocular route, the
      pathogenesis of an ICP22- virus, 22/n199, was altered relative to that of wild
      type virus. Specifically, tear film titers of 22/n199-infected mice were
      significantly reduced at 3 h postinfection relative to those of mice infected
      with wild-type virus. Further, 22/n199 virus titers were below the level of
      detection in trigeminal ganglia (TG) during the first 9 days postinfection. On
      day 30 postinfection, TG from 22/n199-infected mice contained reduced viral
      genome loads and exhibited reduced expression of latency-associated transcripts
      and reduced reactivation efficiency relative to TG from wild-type virus-infected
      mice. Notably, the first detectable alteration in the pathogenesis of 22/n199 in
      these tests occurred in the eye prior to the onset of nascent virus production.
      Thus, ICP22- virions appeared to be degraded, cleared, or adsorbed more rapidly
      than wild-type virions, implying potential differences in the composition of the
      two virion types. Analysis of the protein composition of purified extracellular
      virions indicated that ICP22 is not a virion component and that 22/n199 virions
      sediment at a reduced density relative to wild-type virions. Although similar to
      wild-type virions morphologically, 22/n199 virions contain reduced amounts of two
      gamma2 late proteins, US11 and gC, and increased amounts of two immediate-early
      proteins, ICP0 and ICP4, as well as protein species not detected in wild-type
      virions. Although ICP22- viruses replicate to near-wild-type levels in permissive
      cells, the virions produced in these cells are biochemically and physically
      different from wild-type virions. These virion-specific differences in ICP22-
      viruses add a new level of complexity to the functional analysis of this
      immediate-early viral regulatory protein.

PMID- 16973545
TI  - Cidofovir resistance in vaccinia virus is linked to diminished virulence in mice.
AB  - Cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC)] is
      recognized as a promising drug for the treatment of poxvirus infections, but drug
      resistance can arise by a mechanism that is poorly understood. We show here that
      in vitro selection for high levels of resistance to HPMPC produces viruses
      encoding two substitution mutations in the virus DNA polymerase (E9L) gene. These
      mutations are located within the regions of the gene encoding the 3'-5'
      exonuclease (A314T) and polymerase (A684V) catalytic domains. These mutant
      viruses exhibited cross-resistance to other nucleoside phosphonate drugs, while
      they remained sensitive to other unrelated DNA polymerase inhibitors. Marker
      rescue experiments were used to transfer A314T and/or A684V alleles into a
      vaccinia virus Western Reserve strain. Either mutation alone could confer a drug
      resistance phenotype, although the degree of resistance was significantly lower
      than when virus encoded both mutations. The A684V substitution, but not the A314T
      change, also conferred a spontaneous mutator phenotype. All of the HPMPC
      resistant recombinant viruses exhibited reduced virulence in mice, demonstrating
      that these E9L mutations are inextricably linked to reduced fitness in vivo.
      HPMPC, at a dose of 50 mg/kg of body weight/day for 5 days, still protected mice
      against intranasal challenge with the drug-resistant virus with A314T and A684V
      mutations. Our studies show that proposed drug therapies offer a reasonable
      likelihood of controlling orthopoxvirus infections, even if the viruses encode
      drug resistance markers.

PMID- 16973546
TI  - Invasion of host cells by JC virus identifies a novel role for caveolae in
      endosomal sorting of noncaveolar ligands.
AB  - Invasion of glial cells by the human polyomavirus, JC virus (JCV), leads to a
      rapidly progressing and uniformly fatal demyelinating disease known as
      progressive multifocal leukoencephalopathy. The endocytic trafficking steps used
      by JCV to invade cells and initiate infection are not known. We demonstrated that
      JCV infection was inhibited by dominant defective and constitutively active Rab5
      GTPase mutants that acted at distinct steps in endosomal sorting. We also found
      that labeled JCV colocalized with labeled cholera toxin B and with caveolin-1
      (cav-1) on early endosomes following internalization by clathrin-dependent
      endocytosis. JCV entry and infection were both inhibited by dominant defective
      mutants of eps15 and Rab5-GTPase. Expression of a dominant-negative scaffolding
      mutant of cav-1 did not inhibit entry or infection by JCV. A single-cell
      knockdown experiment using cav-1 shRNA did not inhibit JCV entry but interfered
      with a downstream trafficking event important for infection. These data show that
      JCV enters cells by clathrin-dependent endocytosis, is transported immediately to
      early endosomes, and is then sorted to a caveolin-1-positive endosomal
      compartment. This latter step is dependent on Rab5-GTPase, cholesterol, caveolin
      1, and pH. This is the first example of a ligand that enters cells by clathrin
      dependent endocytosis and is then sorted from early endosomes to caveosomes,
      indicating that caveolae-derived vesicles play a more important role than
      previously realized in sorting cargo from early endosomes.

PMID- 16973547
TI  - Tissue-specific splicing of the herpes simplex virus type 1 latency-associated
      transcript (LAT) intron in LAT transgenic mice.
AB  - To study the regulation of herpes simplex virus type 1 (HSV-1) latency-associated
      transcript (LAT) expression and processing in the absence of other cis and trans
      viral functions, a transgenic mouse containing the region encompassing the LAT
      promoter (LAP1) and the LAT 5' exon through the 2.0-kb intron was created. LAT
      expression was detectable by reverse transcriptase PCR (RT-PCR) in a number of
      tissues, including the dorsal root ganglia (DRG), trigeminal ganglia (TG), brain,
      skin, liver, and kidney. However, when the accumulation of the 2.0-kb LAT intron
      was analyzed at the cellular level by in situ hybridization, little or no
      detectable accumulation was observed in the brain, spinal cord, kidney, or foot,
      although the 2.0-kb LAT intron was detected at high levels (over 90% of neurons)
      in the DRG and TG. Northern blot analysis detected the stable 2.0-kb LAT intron
      only in the sensory ganglia. When relative amounts of the spliced and unspliced
      LAT within the brain, liver, kidney, spinal cord, TG, and DRG were analyzed by
      real-time RT-PCR, splicing of the 2.0-kb LAT intron was significantly more
      efficient in the sensory ganglia than in other tissues. Finally, infection of
      both transgenic mice and nontransgenic littermates with HSV-1 revealed no
      differences in lytic replication, establishment of latency, or reactivation,
      suggesting that expression of the LAT transgene in trans has no significant
      effect on those functions. Taken together, these data indicate that the
      regulation of expression and processing of LAT RNA within the mouse is highly
      cell-type specific and occurs in the absence of other viral cis- and trans-acting
      factors.

PMID- 16973548
TI  - Resistance to alpha/beta interferon is a determinant of West Nile virus
      replication fitness and virulence.
AB  - The emergence of West Nile virus (WNV) in the Western Hemisphere is marked by the
      spread of pathogenic lineage I strains, which differ from typically avirulent
      lineage II strains. To begin to understand the virus-host interactions that may
      influence the phenotypic properties of divergent lineage I and II viruses, we
      compared the genetic, pathogenic, and alpha/beta interferon (IFN-alpha/beta)
      regulatory properties of a lineage II isolate from Madagascar (MAD78) with those
      of a new lineage I isolate from Texas (TX02). Full genome sequence analysis
      revealed that MAD78 clustered, albeit distantly, with other lineage II strains,
      while TX02 clustered with emergent North American isolates, more specifically
      with other Texas strains. Compared to TX02, MAD78 replicated at low levels in
      cultured human cells, was highly sensitive to the antiviral actions of IFN in
      vitro, and demonstrated a completely avirulent phenotype in wild-type mice. In
      contrast to TX02 and other pathogenic forms of WNV, MAD78 was defective in its
      ability to disrupt IFN-induced JAK-STAT signaling, including the activation of
      Tyk2 and downstream phosphorylation and nuclear translocation of STAT1 and STAT2.
      However, replication of MAD78 was rescued in cells with a nonfunctional IFN
      alpha/beta receptor (IFNAR). Consistent with this finding, the virulence of MAD78
      was unmasked upon infection of mice lacking IFNAR. Thus, control of the innate
      host response and IFN actions is a key feature of WNV pathogenesis and
      replication fitness.

PMID- 16973549
TI  - Epstein-Barr virus BNRF1 protein allows efficient transfer from the endosomal
      compartment to the nucleus of primary B lymphocytes.
AB  - Epstein-Barr virus (EBV) is a tumor virus with marked B lymphotropism. After
      crossing the B-cell membrane, the virus enters cytoplasmic vesicles, where
      decapsidation takes place to allow transfer of the viral DNA to the cell nucleus.
      BNRF1 has been characterized as the EBV major tegument protein, but its precise
      function is unknown. We have constructed a viral mutant that lacks the BNRF1 gene
      and report here its in vitro phenotype. A recombinant virus devoid of BNRF1
      (DeltaBNRF1) showed efficient DNA replication and production of mature viral
      particles. B cells infected with the DeltaBNRF1 mutant presented viral lytic
      antigens as efficiently as B cells infected with wild-type or BNRF1 trans
      complemented DeltaBNRF1 viruses. Antigen presentation in B cells infected with
      either wild-type (EBV-wt) or DeltaBNRF1 virus was blocked by leupeptin addition,
      showing that both viruses reach the endosome/lysosome compartment. These data
      were confirmed by direct observation of the mutant virus in endosomes of infected
      B cells by electron microscopy. However, we observed a 20-fold reduction in the
      number of B cells expressing the nuclear protein EBNA2 after infection with a
      DeltaBNRF1 virus compared to wild-type infection. Likewise, DeltaBNRF1 viruses
      transformed primary B cells much less efficiently than EBV-wt or BNRF1 trans
      complemented viruses. We conclude from these findings that BNRF1 plays an
      important role in viral transport from the endosomes to the nucleus.

PMID- 16973550
TI  - Soluble Epstein-Barr virus glycoproteins gH, gL, and gp42 form a 1:1:1 stable
      complex that acts like soluble gp42 in B-cell fusion but not in epithelial cell
      fusion.
AB  - Epstein-Barr virus (EBV) is a herpesvirus that infects cells by fusing its lipid
      envelope with the target cell membrane. The fusion process requires the actions
      of viral glycoproteins gH, gL, and gB for entry into epithelial cells and
      additionally requires gp42 for entry into B cells. To further study the roles of
      these membrane-associated glycoproteins, purified soluble forms of gp42, gH, and
      gL were expressed that lack the membrane-spanning regions. The soluble gH/gL
      protein complex binds to soluble gp42 with high affinity, forming a stable
      heterotrimer with 1:1:1 stoichiometry, and this complex is not formed by an N
      terminally truncated variant of gp42. The effects of adding soluble gp42, gH/gL,
      and gH/gL/gp42 were examined with a virus-free cell-cell fusion assay. The
      results demonstrate that, in contrast to gp42, membrane fusion does not proceed
      with secreted gH/gL. The addition of soluble gH/gL does not inhibit or enhance B
      cell or epithelial cell fusion when membrane-bound gH/gL, gB, and gp42 are
      present. However, the soluble gH/gL/gp42 complex does activate membrane fusion
      with B cells, similarly to soluble gp42, but it does not inhibit fusion with
      epithelial cells, as observed for gp42 alone. A gp42 peptide, derived from an N
      terminal segment involved in gH/gL interactions, binds to soluble gH/gL and
      inhibits EBV-mediated epithelial cell fusion, mimicking gp42. These observations
      reveal distinct functional requirements for gH/gL and gp42 complexes in EBV
      mediated membrane fusion.

PMID- 16973551
TI  - Vaccinia virus F9 virion membrane protein is required for entry but not virus
      assembly, in contrast to the related L1 protein.
AB  - All sequenced poxviruses encode orthologs of the vaccinia virus L1 and F9
      proteins, which are structurally similar and share about 20% amino acid identity.
      We found that F9 further resembles L1 as both proteins are membrane components of
      the mature virion with similar topologies and induce neutralizing antibodies. In
      addition, a recombinant vaccinia virus that inducibly expresses F9, like a
      previously described L1 mutant, had a conditional-lethal phenotype: plaque
      formation and replication of infectious virus were dependent on added inducer.
      However, only immature virus particles are made when L1 is repressed, whereas
      normal-looking intracellular and extracellular virions formed in the absence of
      F9. Except for the lack of F9, the polypeptide components of such virions were
      indistinguishable from those of wild-type virus. These F9-deficient virions bound
      to cells, but their cores did not penetrate into the cytoplasm. Furthermore,
      cells infected with F9-negative virions did not fuse after a brief low-pH
      treatment, as did cells infected with virus made in the presence of inducer. In
      these respects, the phenotype associated with F9 deficiency was identical to that
      produced by the lack of individual components of a previously described poxvirus
      entry/fusion complex. Moreover, F9 interacted with proteins of that complex,
      supporting a related role. Thus, despite the structural relationships of L1 and
      F9, the two proteins have distinct functions in assembly and entry, respectively.

PMID- 16973552
TI  - Human ESCRT-II complex and its role in human immunodeficiency virus type 1
      release.
AB  - The budding of many enveloped RNA viruses, including human immunodeficiency virus
      type 1 (HIV-1), requires some of the same cellular machinery as vesicle formation
      at the multivesicular body (MVB). In Saccharomyces cerevisiae, the ESCRT-II
      complex performs a central role in MVB protein sorting and vesicle formation, as
      it is recruited by the upstream ESCRT-I complex and nucleates assembly of the
      downstream ESCRT-III complex. Here, we report that the three subunits of human
      ESCRT-II, EAP20, EAP30, and EAP45, have a number of properties in common with
      their yeast orthologs. Specifically, EAP45 bound ubiquitin via its N-terminal
      GRAM-like ubiquitin-binding in EAP45 (GLUE) domain, both EAP45 and EAP30 bound
      the C-terminal domain of TSG101/ESCRT-I, and EAP20 bound the N-terminal half of
      CHMP6/ESCRT-III. Consistent with its expected role in MVB vesicle formation, (i)
      human ESCRT-II localized to endosomal membranes in a VPS4-dependent fashion and
      (ii) depletion of EAP20/ESCRT-II and CHMP6/ESCRT-III inhibited lysosomal
      targeting and downregulation of the epidermal growth factor receptor, albeit to a
      lesser extent than depletion of TSG101/ESCRT-I. Nevertheless, HIV-1 release and
      infectivity were not reduced by efficient small interfering RNA depletion of
      EAP20/ESCRT-II or CHMP6/ESCRT-III. These observations indicate that there are
      probably multiple pathways for protein sorting/MVB vesicle formation in human
      cells and that HIV-1 does not utilize an ESCRT-II-dependent pathway to leave the
      cell.

PMID- 16973553
TI  - Essential functions of the unique N-terminal region of the varicella-zoster virus
      glycoprotein E ectodomain in viral replication and in the pathogenesis of skin
      infection.
AB  - Varicella-zoster virus (VZV) glycoprotein E (gE) is a multifunctional protein
      important for cell-cell spread, envelopment, and possibly entry. In contrast to
      other alphaherpesviruses, gE is essential for VZV replication. Interestingly, the
      N-terminal region of gE, comprised of amino acids 1 to 188, was shown not to be
      conserved in the other alphaherpesviruses by bioinformatics analysis. Mutational
      analysis was performed to investigate the functions associated with this unique
      gE N-terminal region. Linker insertions, serine-to-alanine mutations, and
      deletions were introduced in the gE N-terminal region in the VZV genome, and the
      effects of these mutations on virus replication and cell-cell spread, gE
      trafficking and localization, virion formation, and replication in vivo in the
      skin were analyzed. In summary, mutagenesis of the gE N-terminal region
      identified a new functional region in the VZV gE ectodomain essential for cell
      cell spread and the pathogenesis of VZV skin tropism and demonstrated that
      different subdomains of the unique N-terminal region had specific roles in viral
      replication, cell-cell spread, and secondary envelopment.

PMID- 16973554
TI  - Revealing domain structure through linker-scanning analysis of the murine
      leukemia virus (MuLV) RNase H and MuLV and human immunodeficiency virus type 1
      integrase proteins.
AB  - Linker-scanning libraries were generated within the 3' terminus of the Moloney
      murine leukemia virus (M-MuLV) pol gene encoding the connection-RNase H domains
      of reverse transcriptase (RT) as well as the structurally related M-MuLV and
      human immunodeficiency virus type 1 (HIV-1) integrase (IN) proteins. Mutations
      within the M-MuLV proviral vectors were Tn7 based and resulted in 15-bp
      insertions. Mutations within an HIV-1 IN bacterial expression vector were based
      on Tn5 and resulted in 57-bp insertions. The effects of the insertions were
      examined in vivo (M-MuLV) and in vitro (HIV-1). A total of 178 individual M-MuLV
      constructs were analyzed; 40 in-frame insertions within RT connection-RNase H,
      108 in-frame insertions within IN, 13 insertions encoding stop codons within
      RNase H, and 17 insertions encoding stop codons within IN. For HIV-1 IN, 56
      mutants were analyzed. In both M-MuLV and HIV-1 IN, regions are identified which
      functionally tolerate multiple-linker insertions. For MuLV, these correspond to
      the RT-IN proteolytic junction, the junction between the IN core and C terminus,
      and the C terminus of IN. For HIV-1 IN, in addition to the junction between the
      IN core and C terminus and the C terminus of IN, insertions between the N
      terminus and core domains maintained integration and disintegration activity. Of
      the 40 in-frame insertions within the M-MuLV RT connection-RNase H domains, only
      the three C-terminal insertions mapping to the RT-IN proteolytic junction were
      viable. These results correlate with deletion studies mapping the domain and
      subdomain boundaries of RT and IN. Importantly, these genetic footprints provide
      a means to identify nonessential regions within RT and IN for targeted gene
      therapy applications.

PMID- 16973555
TI  - Mapping and functional role of the self-association domain of vesicular
      stomatitis virus phosphoprotein.
AB  - The phosphoprotein (P protein) of vesicular stomatitis virus (VSV) is an
      essential subunit of the viral RNA-dependent RNA polymerase complex and plays a
      central role in viral transcription and replication. Using both the yeast two
      hybrid system and coimmunoprecipitation assays, we confirmed the self-association
      of the P protein of Indiana serotype (Pind) and heterotypic interaction between
      Pind and the P protein of New Jersey serotype (Pnj). Furthermore, by using
      various truncation and deletion mutants of Pind, the self-association domain of
      the Pind protein was mapped to amino acids 161 to 210 within the hinge region.
      The self-association domain of Pind protein is not required for its binding to
      nucleocapsid and large proteins. We further demonstrated that the self
      association domain of Pind protein is essential for VSV transcription in a
      minireplicon system and that a synthetic peptide spanning amino acids 191 to 210
      in the self-association domain of Pind protein strongly inhibited the
      transcription of the VSV genome in vitro in a dose-dependent manner. These
      results indicated that the self-association domain of Pind protein plays a
      critical role in VSV transcription.

PMID- 16973556
TI  - Selection on the human immunodeficiency virus type 1 proteome following primary
      infection.
AB  - Typically during human immunodeficiency virus type 1 (HIV-1) infection, a nearly
      homogeneous viral population first emerges and then diversifies over time due to
      selective forces that are poorly understood. To identify these forces, we
      conducted an intensive longitudinal study of viral genetic changes and T-cell
      immunity in one subject at < or =17 time points during his first 3 years of
      infection, and in his infecting partner near the time of transmission. Autologous
      peptides covering amino acid sites inferred to be under positive selection were
      powerful for identifying HIV-1-specific cytotoxic-T-lymphocyte (CTL) epitopes.
      Positive selection and mutations resulting in escape from CTLs occurred across
      the viral proteome. We detected 25 CTL epitopes, including 14 previously
      unreported. Seven new epitopes mapped to the viral Env protein, emphasizing Env
      as a major target of CTLs. One-third of the selected sites were associated with
      epitopic mutational escapes from CTLs. Most of these resulted from replacement
      with amino acids found at low database frequency. Another one-third represented
      acquisition of amino acids found at high database frequency, suggesting potential
      reversions of CTL epitopic sites recognized by the immune system of the
      transmitting partner and mutation toward improved viral fitness in the absence of
      immune targeting within the recipient. A majority of the remaining selected sites
      occurred in the envelope protein and may have been subjected to humoral immune
      selection. Hence, a majority of the amino acids undergoing selection in this
      subject appeared to result from fitness-balanced CTL selection, confirming CTLs
      as a dominant selective force in HIV-1 infection.

PMID- 16973557
TI  - Brd4 is required for e2-mediated transcriptional activation but not genome
      partitioning of all papillomaviruses.
AB  - Bromodomain protein 4 (Brd4) has been identified as the cellular binding target
      through which the E2 protein of bovine papillomavirus type 1 links the viral
      genome to mitotic chromosomes. This tethering ensures retention and efficient
      partitioning of genomes to daughter cells following cell division. E2 is also a
      regulator of viral gene expression and a replication factor, in association with
      the viral E1 protein. In this study, we show that E2 proteins from a wide range
      of papillomaviruses interact with Brd4, albeit with variations in efficiency.
      Moreover, disruption of the E2-Brd4 interaction abrogates the transactivation
      function of E2, indicating that Brd4 is required for E2-mediated transactivation
      of all papillomaviruses. However, the interaction of E2 and Brd4 is not required
      for genome partitioning of all papillomaviruses since a number of papillomavirus
      E2 proteins associate with mitotic chromosomes independently of Brd4 binding.
      Furthermore, mutations in E2 that disrupt the interaction with Brd4 do not affect
      the ability of these E2s to associate with chromosomes. Thus, while all
      papillomaviruses attach their genomes to cellular chromosomes to facilitate
      genome segregation, they target different cellular binding partners. In summary,
      the E2 proteins from many papillomaviruses, including the clinically important
      alpha genus human papillomaviruses, interact with Brd4 to mediate transcriptional
      activation function but not all depend on this interaction to efficiently
      associate with mitotic chromosomes.

PMID- 16973558
TI  - Delayed biosynthesis of varicella-zoster virus glycoprotein C: upregulation by
      hexamethylene bisacetamide and retinoic acid treatment of infected cells.
AB  - In the course of examining the trafficking pathways of varicella-zoster virus
      (VZV) glycoproteins gE, gI, gH, and gB, we discovered that all four are
      synthesized within 4 to 6 h postinfection (hpi) in cultured cells. Thereafter,
      they travel via the trans-Golgi network to the outer cell membrane. When we
      carried out a similar analysis on VZV gC, we observed little gC biosynthesis in
      the first 72 hpi. Further examination disclosed that gC was present in the
      inocula of infected cells, but no new gC biosynthesis occurred during the first
      24 to 48 h thereafter, during which time new synthesis of gE, gH, and major
      capsid protein was easily detectable. Similarly, delayed gC biosynthesis was
      confirmed with three different VZV strains and two different cell lines.
      Bioinformatics analyses disclosed the presence of PBX/HOX consensus binding
      domains in the promoter/enhancer regions of the genes for VZV gC and ORF4 protein
      (whose orthologs transactivate gC in other herpesviruses). Bioinformatics
      analysis also identified two HOXA9 activation regions on ORF4 protein. Treatment
      of infected cultures with chemicals known to induce the production of PBX/HOX
      transcription proteins, namely, hexamethylene bisacetamide (HMBA) and retinoic
      acid, led to more rapid gC biosynthesis. Immunoblotting demonstrated a fivefold
      increase in the HOXA9 protein after HMBA treatment. In summary, these results
      documented that gC was not produced during early VZV replication cycles,
      presumably related to a deficiency in the PBX/HOX transcription factors.
      Furthermore, these results explain the apparent spontaneous loss of VZV gC in
      some passaged viruses, as well as other anomalous gC results.

PMID- 16973559
TI  - Cryptic properties of a cluster of dominant flavivirus cross-reactive antigenic
      sites.
AB  - A number of flaviviruses are important human pathogens, including yellow fever,
      dengue, West Nile, Japanese encephalitis, and tick-borne encephalitis (TBE)
      viruses. Infection with or immunization against any of these viruses induces a
      subset of antibodies that are broadly flavivirus cross-reactive but do not
      exhibit significant cross-neutralization. Nevertheless, these antibodies can
      efficiently bind to the major envelope protein (E), which is the main target of
      neutralizing and protective antibodies because of its receptor-binding and
      membrane fusion functions. The structural basis for this phenomenon is still
      unclear. In our studies with TBE virus, we have provided evidence that such cross
      reactive antibodies are specific for a cluster of epitopes that are partially
      occluded in the cage-like assembly of E proteins at the surfaces of infectious
      virions and involve-but are not restricted to-amino acids of the highly conserved
      internal fusion peptide loop. Virus disintegration leads to increased
      accessibility of these epitopes, allowing the cross-reactive antibodies to bind
      with strongly increased avidity. The cryptic properties of these sites in the
      context of infectious virions can thus provide an explanation for the observed
      lack of efficient neutralizing activity of broadly cross-reactive antibodies,
      despite their specificity for a functionally important structural element in the
      E protein.

PMID- 16973560
TI  - Complete-genome phylogenetic approach to varicella-zoster virus evolution:
      genetic divergence and evidence for recombination.
AB  - Recent studies of varicella-zoster virus (VZV) DNA sequence variation, involving
      large numbers of globally distributed clinical isolates, suggest that this virus
      has diverged into at least three distinct genotypes designated European (E),
      Japanese (J), and mosaic (M). In the present study, we determined and analyzed
      the complete genomic sequences of two M VZV strains and compared them to the
      sequences of three E strains and two J strains retrieved from GenBank (including
      the Oka vaccine preparation, V-Oka). Except for a few polymorphic tandem repeat
      regions, the whole genome, representing approximately 125,000 nucleotides, is
      highly conserved, presenting a genetic similarity between the E and J genotypes
      of approximately 99.85%. These analyses revealed that VZV strains distinctly
      segregate into at least four genotypes (E, J, M1, and M2) in phylogenetic trees
      supported by high bootstrap values. Separate analyses of informative sites
      revealed that the tree topology was dependent on the region of the VZV genome
      used to determine the phylogeny; collectively, these results indicate the
      observed strain variation is likely to have resulted, at least in part, from
      interstrain recombination. Recombination analyses suggest that strains belonging
      to the M1 and M2 genotypes are mosaic recombinant strains that originated from
      ancestral isolates belonging to the E and J genotypes through recombination on
      multiple occasions. Furthermore, evidence of more recent recombination events
      between M1 and M2 strains is present in six segments of the VZV genome. As such,
      interstrain recombination in dually infected cells seems to figure prominently in
      the evolutionary history of VZV, a feature it has in common with other
      herpesviruses. In addition, we report here six novel genomic targets located in
      open reading frames 51 to 58 suitable for genotyping of clinical VZV isolates.

PMID- 16973561
TI  - Characterization of antibody responses to combinations of a dengue virus type 2
      DNA vaccine and two dengue virus type 2 protein vaccines in rhesus macaques.
AB  - We evaluated three nonreplicating dengue virus type 2 (DENV-2) vaccines: (i) a
      DNA vaccine containing the prM-E gene region (D), (ii) a recombinant subunit
      protein vaccine containing the B domain (i.e., domain III) of the E protein as a
      fusion with the Escherichia coli maltose-binding protein (R), and (iii) a
      purified inactivated virus vaccine (P). Groups of four rhesus macaques each were
      primed once and boosted twice using seven different vaccination regimens. After
      primary vaccination, enzyme-linked immunosorbent assay (ELISA) antibody levels
      increased most rapidly for groups inoculated with the P and DP combination, and
      by 1 month after the second boost, ELISA titers were similar for all groups. The
      highest plaque reduction neutralization test (PRNT) titers were seen in those
      groups that received the DR/DR/DR combination (geometric mean titer [GMT], 510),
      the P/P/P vaccine (GMT, 345), the DP/DP/DP combination (GMT, 287), and the R/R/R
      vaccine (GMT, 200). The next highest titers were seen in animals that received
      the D/R/R vaccine (GMT, 186) and the D/P/P vaccine (GMT, 163). Animals that
      received the D/D/D vaccine had the lowest neutralizing antibody titer (GMT, 49).
      Both ELISA and PRNT titers declined at variable rates. The only significant
      protection from viremia was observed in the P-vaccinated animals (mean of 0.5
      days), which also showed the highest antibody concentration, including antibodies
      to NS1, and highest antibody avidity at the time of challenge.

PMID- 16973562
TI  - Human immunodeficiency virus type 1 V1-V2 envelope loop sequences expand and add
      glycosylation sites over the course of infection, and these modifications affect
      antibody neutralization sensitivity.
AB  - Over the course of infection, human immunodeficiency virus type 1 (HIV-1)
      continuously adapts to evade the evolving host neutralizing antibody responses.
      Changes in the envelope variable loop sequences, particularly the extent of
      glycosylation, have been implicated in antibody escape. To document modifications
      that potentially influence antibody susceptibility, we compared envelope variable
      loops 1 and 2 (V1-V2) from multiple sequences isolated at the primary phase of
      infection to those isolated around 2 to 3 years into the chronic phase of
      infection in nine women with HIV-1 subtype A. HIV-1 sequences isolated during
      chronic infection had significantly longer V1-V2 loops, with a significantly
      higher number of potential N-linked glycosylation sites, than the sequences
      isolated early in infection. To assess the effects of these V1-V2 changes on
      antibody neutralization and infectivity, we created chimeric envelope sequences,
      which incorporated a subject's V1-V2 sequences into a common subtype A envelope
      backbone and then used them to generate pseudotyped viruses. Compared to the
      parent virus, the introduction of a subject's early-infection V1-V2 envelope
      variable loops rendered the chimeric envelope more sensitive to that subject's
      plasma samples but only to plasma samples collected >6 months after the sequences
      were isolated. Neutralization was not detected with the same plasma when the
      early-infection V1-V2 sequences were replaced with chronic-infection V1-V2
      sequences, suggesting that changes in V1-V2 contribute to antibody escape.
      Pseudotyped viruses with V1-V2 segments from different times in infection,
      however, showed no significant difference in neutralization sensitivity to
      heterologous pooled plasma, suggesting that viruses with V1-V2 loops from early
      in infection were not inherently more neutralization sensitive. Pseudotyped
      viruses bearing chimeric envelopes with early-infection V1-V2 sequences showed a
      trend in infecting cells with low CD4 concentrations more efficiently, while
      engineered viruses with V1-V2 sequences isolated during chronic infection were
      moderately better at infecting cells with low CCR5 concentrations. These studies
      suggest that changes within the V1-V2 envelope domains over the course of an
      infection influence sensitivity to autologous neutralizing antibodies and may
      also impact host receptor/coreceptor interactions.

PMID- 16973563
TI  - Site-directed antibodies against the stem region reveal low pH-induced
      conformational changes of the Semliki Forest virus fusion protein.
AB  - The E1 envelope protein of the alphavirus Semliki Forest virus (SFV) is a class
      II fusion protein that mediates low pH-triggered membrane fusion during virus
      infection. Like other class I and class II fusion proteins, during fusion E1
      inserts into the target membrane and rearranges to form a trimeric hairpin
      structure. The postfusion structures of the alphavirus and flavivirus fusion
      proteins suggest that the "stem" region connecting the fusion protein domain III
      to the transmembrane domain interacts along the trimer core during the low pH
      induced conformational change. However, the location of the E1 stem in the SFV
      particle and its rearrangement and functional importance during fusion are not
      known. We developed site-directed polyclonal antibodies to the N- or C-terminal
      regions of the SFV E1 stem and used them to study the stem during fusion. The E1
      stem was hidden on neutral pH virus but became accessible after low pH-triggered
      dissociation of the E2/E1 heterodimer. The stem packed onto the trimer core in
      the postfusion conformation and became inaccessible to antibody binding.
      Generation of the E1 homotrimer on fusion-incompetent membranes identified an
      intermediate conformation in which domain III had folded back but stem packing
      was incomplete. Our data suggest that E1 hairpin formation occurs by the
      sequential packing of domain III and the stem onto the trimer core and indicate a
      tight correlation between stem packing and membrane merger.

PMID- 16973564
TI  - Adenovirus core protein pVII is translocated into the nucleus by multiple import
      receptor pathways.
AB  - Adenoviruses are nonenveloped viruses with an approximately 36-kb double-stranded
      DNA genome that replicate in the nucleus. Protein VII, an abundant structural
      component of the adenovirus core that is strongly associated with adenovirus DNA,
      is imported into the nucleus contemporaneously with the adenovirus genome shortly
      after virus infection and may promote DNA import. In this study, we evaluated
      whether protein VII uses specific receptor-mediated mechanisms for import into
      the nucleus. We found that it contains potent nuclear localization signal (NLS)
      activity by transfection of cultured cells with protein VII fusion constructs and
      by microinjection of cells with recombinant protein VII fusions. We identified
      three NLS-containing regions in protein VII by deletion mapping and determined
      important NLS residues by site-specific mutagenesis. We found that recombinant
      protein VII and its NLS-containing domains strongly and specifically bind to
      importin alpha, importin beta, importin 7, and transportin, which are among the
      most abundant cellular nuclear import receptors. Moreover, these receptors can
      mediate the nuclear import of protein VII fusions in vitro in permeabilized
      cells. Considered together, these data support the hypothesis that protein VII is
      a major NLS-containing adaptor for receptor-mediated import of adenovirus DNA and
      that multiple import pathways are utilized to promote efficient nuclear entry of
      the viral genome.

PMID- 16973565
TI  - An antiviral peptide inhibitor that is active against picornavirus 2A proteinases
      but not cellular caspases.
AB  - The replication of many viruses is absolutely dependent on proteolytic cleavage.
      Infected cells also use this biological mechanism to induce programmed cell death
      in response to viral infection. Specific inhibitors for both viral and cellular
      proteases are therefore of vital importance. We have recently shown that the
      general caspase inhibitor zVAD.fmk inhibits not only caspases, but also the 2Apro
      of human rhinoviruses (HRVs) (L. Deszcz, J. Seipelt, E. Vassilieva, A. Roetzer,
      and E. Kuechler, FEBS Lett. 560:51-55, 2004). Here, we describe a derivative of
      zVAD.fmk that inhibits HRV2 2Apro but that has no effect on caspase 9. This gain
      in specificity was achieved by replacing the aspartic acid of zVAD.fmk with
      methionine to generate zVAM.fmk. Methionine was chosen because an oligopeptide
      with methionine at the P1 position was a much better substrate than an
      oligopeptide with an alanine residue, which is found at the P1 position of the
      wild-type HRV2 2Apro cleavage site. zVAM.fmk inhibits the replication of HRV type
      2 (HRV2), HRV14, and HRV16. In contrast to zVAD.fmk, however, zVAM.fmk did not
      inhibit apoptosis induced by puromycin in HeLa cells. zVAM.fmk inhibited in vitro
      the intermolecular cleavage of eukaryotic initiation factor 4GI (eIF4GI) by HRV2
      2Apro at nanomolar concentrations. However, much higher concentrations of
      zVAM.fmk were required to inhibit HRV14 2Apro cleavage of eIF4GI. In contrast,
      intramolecular self-processing of HRV14 2Apro was much more susceptible to
      inhibition by zVAM.fmk than that of HRV2 2Apro, suggesting that zVAM.fmk inhibits
      HRV2 and HRV14 replication by targeting different reactions of the same
      proteinase.

PMID- 16973566
TI  - Antibodies to gp350/220 enhance the ability of Epstein-Barr virus to infect
      epithelial cells.
AB  - Epstein-Barr virus (EBV) is a persistent, orally transmitted herpesvirus that
      replicates in B cells and epithelial cells and is associated with lymphoid and
      epithelial malignancies. The virus binds to CD21 on B cells via glycoprotein
      gp350/220 and infects efficiently. Infection of cultured epithelial cells has not
      typically been efficient but can occur in the absence of gp350/220 and CD21 and
      in vivo is thought to be important to the development of nasopharyngeal
      carcinoma. We report here that antibodies to gp350/220, which inhibit EBV
      infection of B cells, enhance infection of epithelial cells. The effect is not
      mediated by Fc receptor binding but is further enhanced by antibody cross
      linking, which may patch gp350/220 in the virus envelope. Saliva from EBV
      seropositive individuals has similar effects that can be reversed by depletion of
      antibody. The results are consistent with a model in which gp350/220 interferes
      with the access of other important players to the epithelial cell surface. The
      results may have implications for the development of nasopharyngeal carcinoma in
      high-risk populations in which elevated titers of antibody to EBV lytic cycle
      proteins are prognostic.

PMID- 16973567
TI  - The negative regulator of splicing element of Rous sarcoma virus promotes
      polyadenylation.
AB  - The Rous sarcoma virus gag gene contains a cis-acting negative regulator of
      splicing (NRS) element that is implicated in viral polyadenylation regulation. To
      study the mechanism of polyadenylation promotion at the viral poly(A) site
      located over 8 kb downstream, we performed in vitro polyadenylation analysis. RNA
      containing only the poly(A) site and flanking sequences in the 3' long terminal
      repeat (LTR) was not polyadenylated detectably in vitro; however, if the
      transcript contained the NRS upstream of the LTR, polyadenylation was observed.
      Insertion of the viral env 3' splice site sequence between the NRS and the LTR
      did not alter the level of polyadenylation appreciably. We conclude that the NRS
      promotes polyadenylation in vitro and can do so without formation of a splicing
      complex with a 3' splice site. We then explored the roles of several cellular
      factors in NRS-mediated polyadenylation. Mutation of the binding sites of U1 and
      U11 snRNPs to the NRS did not affect polyadenylation, whereas hnRNP H strongly
      inhibited polyadenylation. We propose a model in which hnRNP H and SR proteins
      compete for binding to the NRS. Bound SR proteins may bridge between the NRS and
      the 3' LTR and aid in the recruitment of the 3'-end processing machinery.

PMID- 16973568
TI  - Complementation of human immunodeficiency virus type 1 replication by
      intracellular selection of Escherichia coli formula supplied in trans.
AB  - Human immunodeficiency virus type 1 (HIV-1) exclusively selects tRNA3Lys as the
      primer for the initiation of reverse transcription, even though both tRNA3Lys and
      tRNA1,2Lys are found in HIV-1 virions. Alteration of the HIV-1 primer-binding
      site (PBS) to be complementary to alternate tRNAs results in the use of those
      tRNAs for replication, indicating that primer complementarity with the PBS is an
      important determinant of primer selection. In previous studies, we have exploited
      this fact to develop a system in which yeast (Saccharomyces cerevisiae) tRNAPhe
      is provided in trans to complement the replication of HIV-1 with a PBS
      complementary to yeast tRNAPhe. Recent studies have demonstrated that the
      presence of lysyl-tRNA synthetase in HIV-1 virions might account for the
      preference for the selection of tRNA3Lys in HIV-1 replication. To establish a
      complementation system more reflective of HIV-1 primer selection, we have altered
      the HIV-1 PBS to be complementary to the Escherichia coli tRNA3Lys, which shares
      near identity with mammalian tRNA3Lys except in the 3'-terminal 18-nucleotide
      sequence that binds to the PBS. E. coli tRNA3Lys expressed from a plasmid was
      aminoacylated in mammalian cells. Cotransfection of cells with a plasmid that
      encodes E. coli tRNA3Lys and a plasmid encoding an HIV-1 provirus with a PBS
      complementary to E. coli tRNA3Lys resulted in the production of infectious virus.
      A comparison of the two complementation systems revealed that higher levels of
      intracellular E. coli tRNA3Lys than of yeast tRNAPhe were needed to achieve equal
      levels of infectious virus, indicating that there was no preferential selection
      of E. coli tRNA3Lys. To examine the specificity of tRNALys selection, E. coli
      tRNA3Lys was modified to tRNA1,2Lys. This tRNA was also aminoacylated when
      expressed in mammalian cells and complemented the infectivity of HIV-1 at levels
      similar to those seen for E. coli tRNA3Lys. Additional mutations in the anticodon
      of E. coli tRNA3Lys were constructed; these mutations did not significantly
      correlate with the capacity of the tRNA primer to complement infectivity of HIV
      1, even though they had a drastic effect on the aminoacylation of the tRNAs. The
      results of these studies demonstrate that E. coli tRNA3Lys provided in trans can
      complement HIV-1 genomes with the PBS altered to E. coli tRNA3Lys. However, the
      capacity of tRNA3Lys to interact with lysyl-tRNA synthetase does not entirely
      explain the enhanced preference for selection of tRNA3Lys for the replication of
      HIV-1.

PMID- 16973569
TI  - High frequency of genetic recombination is a common feature of primate lentivirus
      replication.
AB  - Recent studies indicate that human immunodeficiency virus type 1 (HIV-1)
      recombines at exceedingly high rates, approximately 1 order of magnitude more
      frequently than simple gammaretroviruses such as murine leukemia virus and spleen
      necrosis virus. We hypothesize that this high frequency of genetic recombination
      is a common feature of primate lentiviruses. Alternatively, it is possible that
      HIV-1 is unique among primate lentiviruses in possessing high recombination
      rates. Among other primate lentiviruses, only the molecular mechanisms of HIV-2
      replication have been extensively studied. There are reported differences between
      the replication mechanisms of HIV-1 and those of HIV-2, such as preferences for
      RNA packaging in cis and properties of reverse transcriptase and RNase H
      activities. These biological disparities could lead to differences in
      recombination rates between the two viruses. Currently, HIV-1 is the only primate
      lentivirus in which recombination rates have been measured. To test our
      hypothesis, we established recombination systems to measure the recombination
      rates of two other primate lentiviruses, HIV-2 and simian immunodeficiency virus
      from African green monkeys (SIVagm), in one round of viral replication. We
      determined that, for markers separated by 588, 288, and 90 bp, HIV-2 recombined
      at rates of 7.4%, 5.5%, and 2.4%, respectively, whereas SIVagm recombined at
      rates of 7.8%, 5.6%, and 2.7%, respectively. These high recombination rates are
      within the same range as the previously measured HIV-1 recombination rates. Taken
      together, our results indicate that HIV-1, HIV-2, and SIVagm all possess high
      recombination frequencies; hence, the high recombination potential is most likely
      a common feature of primate lentivirus replication.

PMID- 16973570
TI  - Cross-protection against Marburg virus strains by using a live, attenuated
      recombinant vaccine.
AB  - Marburg virus (MARV) has been associated with sporadic episodes of hemorrhagic
      fever, including a recent highly publicized outbreak in Angola that produced
      severe disease and significant mortality in infected patients. MARV is also
      considered to have potential as a biological weapon. Recently, we reported the
      development of a promising attenuated, replication-competent vaccine against MARV
      based on recombinant vesicular stomatitis virus (VSV) expressing the glycoprotein
      of the Musoke strain of MARV (VSVDeltaG/MARVGP-Musoke). We used this vaccine to
      demonstrate complete protection of cynomolgus monkeys against a homologous MARV
      challenge. While these results are highly encouraging, an effective vaccine would
      need to confer protection against all relevant strains of MARV. Here, we
      evaluated the protective efficacy of the VSVDeltaG/MARVGP-Musoke vaccine against
      two heterologous MARV strains, the seemingly more pathogenic Angola strain and
      the more distantly related Ravn strain. In this study, seven cynomolgus monkeys
      were vaccinated with the VSVDeltaG/MARVGP-Musoke vector. Three of these animals
      were challenged with the Angola strain, three with the Ravn strain, and a single
      animal with the Musoke strain of MARV. Two animals served as controls and were
      each injected with a nonspecific VSV vector; these controls were challenged with
      the Angola and Ravn strains, respectively. Both controls succumbed to challenge
      by day 8. However, none of the specifically vaccinated animals showed any
      evidence of illness either from the vaccination or from the MARV challenges and
      all of these animals survived. These data suggest that the VSVDeltaG/MARVGP
      Musoke vaccine should be sufficient to protect against all known MARV strains.

PMID- 16973571
TI  - Interaction of Bunyamwera Orthobunyavirus NSs protein with mediator protein MED8:
      a mechanism for inhibiting the interferon response.
AB  - The NSs protein of Bunyamwera virus (Bunyaviridae) is an antiapoptotic interferon
      antagonist involved in silencing host protein expression by interfering with mRNA
      synthesis. Here, we show that the ability to inhibit both host transcription and
      the interferon response is linked to interaction of NSs with the MED8 component
      of Mediator, a protein complex necessary for mRNA production. The interacting
      domain on NSs was mapped to the C-terminal region, which contains amino acids
      conserved among orthobunyavirus NSs proteins. A recombinant virus in which the
      interacting domain in NSs was deleted had strongly reduced ability to inhibit
      host protein expression and was unable to inhibit the interferon response. This
      study provides further information on the mechanisms by which bunyavirus
      nonstructural proteins are involved in pathogenesis.

PMID- 16973572
TI  - The pathogenic NY-1 hantavirus G1 cytoplasmic tail inhibits RIG-I- and TBK-1
      directed interferon responses.
AB  - Hantaviruses cause two diseases with prominent vascular permeability defects,
      hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. All
      hantaviruses infect human endothelial cells, although it is unclear what
      differentiates pathogenic from nonpathogenic hantaviruses. We observed dramatic
      differences in interferon-specific transcriptional responses between pathogenic
      and nonpathogenic hantaviruses at 1 day postinfection, suggesting that hantavirus
      pathogenesis may in part be determined by viral regulation of cellular interferon
      responses. In contrast to pathogenic NY-1 virus (NY-1V) and Hantaan virus (HTNV),
      nonpathogenic Prospect Hill virus (PHV) elicits early interferon responses
      following infection of human endothelial cells. We determined that PHV
      replication is blocked in human endothelial cells and that RNA and protein
      synthesis by PHV, but not NY-1V or HTNV, is inhibited at 2 to 4 days
      postinfection. The addition of antibodies to beta interferon (IFN-beta) blocked
      interferon-directed MxA induction by >90% and demonstrated that hantavirus
      infection induces the secretion of IFN-beta from endothelial cells. Coinfecting
      endothelial cells with NY-1V and PHV resulted in a 60% decrease in the induction
      of interferon-responsive MxA transcripts by PHV and further suggested the
      potential for NY-1V to regulate early IFN responses. Expression of the NY-1V G1
      cytoplasmic tail inhibited by >90% RIG-I- and downstream TBK-1-directed
      transcription from interferon-stimulated response elements or beta-interferon
      promoters in a dose-dependent manner. In contrast, expression of the NY-1V
      nucleocapsid or PHV G1 tail had no effect on RIG-I- or TBK-1-directed
      transcriptional responses. Further, neither the NY-1V nor PHV G1 tails inhibited
      transcriptional responses directed by a constitutively active form of interferon
      regulatory factor 3 (IRF-3 5D), and IRF-3 is a direct target of TBK-1
      phosphorylation. These findings indicate that the pathogenic NY-1V G1 protein
      regulates cellular IFN responses upstream of IRF-3 phosphorylation at the level
      of the TBK-1 complex. These findings further suggest that the G1 cytoplasmic tail
      contains a virulence element which determines the ability of hantaviruses to
      bypass innate cellular immune responses and delineates a mechanism for pathogenic
      hantaviruses to successfully replicate within human endothelial cells.

PMID- 16973573
TI  - Reduction of the rate of poliovirus protein synthesis through large-scale codon
      deoptimization causes attenuation of viral virulence by lowering specific
      infectivity.
AB  - Exploring the utility of de novo gene synthesis with the aim of designing stably
      attenuated polioviruses (PV), we followed two strategies to construct PV variants
      containing synthetic replacements of the capsid coding sequences either by
      deoptimizing synonymous codon usage (PV-AB) or by maximizing synonymous codon
      position changes of the existing wild-type (wt) poliovirus codons (PV-SD).
      Despite 934 nucleotide changes in the capsid coding region, PV-SD RNA produced
      virus with wild-type characteristics. In contrast, no viable virus was recovered
      from PV-AB RNA carrying 680 silent mutations, due to a reduction of genome
      translation and replication below a critical level. After subcloning of smaller
      portions of the AB capsid coding sequence into the wt background, several viable
      viruses were obtained with a wide range of phenotypes corresponding to their
      efficiency of directing genome translation. Surprisingly, when inoculated with
      equal infectious doses (PFU), even the most replication-deficient viruses
      appeared to be as pathogenic in PV-sensitive CD155tg (transgenic) mice as the
      PV(M) wild type. However, infection with equal amounts of virus particles
      revealed a neuroattenuated phenotype over 100-fold. Direct analysis indicated a
      striking reduction of the specific infectivity of PV-AB-type virus particles. Due
      to the distribution effect of many silent mutations over large genome segments,
      codon-deoptimized viruses should have genetically stable phenotypes, and they may
      prove suitable as attenuated substrates for the production of poliovirus
      vaccines.

PMID- 16973574
TI  - Kaposi's Sarcoma-associated herpesvirus lytic switch protein stimulates DNA
      binding of RBP-Jk/CSL to activate the Notch pathway.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) lytic switch protein, Rta, is a
      ligand-independent inducer of the Notch signal transduction pathway, and KSHV
      cannot reactivate from latency in cells null for the Notch target protein RBP-Jk.
      Here we show that Rta promotes DNA binding of RBP-Jk, a mechanism that is
      fundamentally different from that established for the RBP-Jk-activating proteins,
      Notch intracellular domain (NICD) and Epstein-Barr virus EBNA2. Although
      constitutively active RBP-Jk and NICD do not transactivate KSHV promoters
      independently, cotransfection of an Rta mutant lacking its transactivation domain
      robustly restores transcriptional activation. Cooperation requires intact DNA
      binding sites for Rta and RBP-Jk and trimeric complex formation between the three
      molecules in vitro. In infected cells, RBP-Jk is virtually undetectable on a
      series of viral and cellular promoters during KSHV latency but is significantly
      enriched following Rta expression during viral reactivation. Accordingly, Rta,
      but not EBNA2 and NICD, reactivates the complete viral lytic cycle.

PMID- 16973575
TI  - Peripheral blood B-cell death compensates for excessive proliferation in lymphoid
      tissues and maintains homeostasis in bovine leukemia virus-infected sheep.
AB  - The size of a lymphocyte population is primarily determined by a dynamic
      equilibrium between cell proliferation and death. Hence, lymphocyte recirculation
      between the peripheral blood and lymphoid tissues is a key determinant in the
      maintenance of cell homeostasis. Insights into these mechanisms can be gathered
      from large-animal models, where lymphatic cannulation from individual lymph nodes
      is possible. In this study, we assessed in vivo lymphocyte trafficking in bovine
      leukemia virus (BLV)-infected sheep. With a carboxyfluorescein diacetate
      succinimidyl ester labeling technique, we demonstrate that the dynamics of
      lymphocyte recirculation is unaltered but that accelerated proliferation in the
      lymphoid tissues is compensated for by increased death in the peripheral blood
      cell population. Lymphocyte homeostasis is thus maintained by biphasic kinetics
      in two distinct tissues, emphasizing a very dynamic process during BLV infection.

PMID- 16973576
TI  - Herpes simplex virus ICP27 is required for virus-induced stabilization of the ARE
      containing IEX-1 mRNA encoded by the human IER3 gene.
AB  - Herpes simplex virus (HSV) stifles cellular gene expression during productive
      infection of permissive cells, thereby diminishing host responses to infection.
      Host shutoff is achieved largely through the complementary actions of two viral
      proteins, ICP27 and virion host shutoff (vhs), that inhibit cellular mRNA
      biogenesis and trigger global mRNA decay, respectively. Although most cellular
      mRNAs are thus depleted, some instead increase in abundance after infection;
      perhaps surprisingly, some of these contain AU-rich instability elements (AREs)
      in their 3'-untranslated regions. ARE-containing mRNAs normally undergo rapid
      decay; however, their stability can increase in response to signals such as
      cytokines and virus infection that activate the p38/MK2 mitogen-activated protein
      kinase (MAPK) pathway. We and others have shown that HSV infection stabilizes the
      ARE mRNA encoding the stress-inducible IEX-1 mRNA, and a previous report from
      another laboratory has suggested vhs is responsible for this effect. However, we
      now report that ICP27 is essential for IEX-1 mRNA stabilization whereas vhs plays
      little if any role. A recent report has documented that ICP27 activates the p38
      MAPK pathway, and we detected a strong correlation between this activity and
      stabilization of IEX-1 mRNA by using a panel of HSV type 1 (HSV-1) isolates
      bearing an array of previously characterized ICP27 mutations. Furthermore, IEX-1
      mRNA stabilization was abrogated by the p38 inhibitor SB203580. Taken together,
      these data indicate that the HSV-1 immediate-early protein ICP27 alters turnover
      of the ARE-containing message IEX-1 by activating p38. As many ARE mRNAs encode
      proinflammatory cytokines or other immediate-early response proteins, some of
      which may limit viral replication, it will be of great interest to determine if
      ICP27 mediates stabilization of many or all ARE-containing mRNAs.

PMID- 16973577
TI  - ORF18 is a transfactor that is essential for late gene transcription of a
      gammaherpesvirus.
AB  - Lytic replication of the tumor-associated human gammaherpesviruses Epstein-Barr
      virus and Kaposi's sarcoma-associated herpesvirus has important implications in
      pathogenesis and tumorigenesis. Herpesvirus lytic genes have been temporally
      classified as exhibiting immediate-early (IE), early, and late expression
      kinetics. Though the regulation of IE and early gene expression has been studied
      extensively, very little is known regarding the regulation of late gene
      expression. Late genes, which primarily encode virion structural proteins,
      require viral DNA replication for their expression. We have identified a murine
      gammaherpesvirus 68 (MHV-68) early lytic gene, ORF18, essential for viral
      replication. ORF18 is conserved in both beta- and gammaherpesviruses. By
      generating an MHV-68 ORF18-null virus, we characterized the stage of the virus
      lytic cascade that requires the function of ORF18. Gene expression profiling and
      quantitation of viral DNA synthesis of the ORF18-null virus revealed that the
      expression of early genes and viral DNA replication were not affected; however,
      the transcription of late genes was abolished. Hence, we have identified a
      gammaherpesvirus-encoded factor essential for the expression of late genes
      independently of viral DNA synthesis.

PMID- 16973578
TI  - Reconstitution of herpes simplex virus type 1 nuclear capsid egress in vitro.
AB  - Newly assembled herpesvirus capsids travel from the nucleus to the plasma
      membrane by a mechanism that is poorly understood. Furthermore, the contribution
      of cellular proteins to this egress has yet to be clarified. To address these
      issues, an in vitro nuclear egress assay that reproduces the exit of herpes
      simplex virus type 1 (HSV-1) capsids from nuclei isolated from infected cells was
      established. As expected, the assay has all the hallmarks of intracellular
      transport assays, namely, a dependence on time, energy, and temperature.
      Surprisingly, it is also dependent on cytosol and was slightly enhanced by
      infected cytosol, suggesting an implication of both host and viral proteins in
      the process. The capsids escaped these nuclei by budding through the inner
      nuclear membrane, accumulated as enveloped capsids between the two nuclear
      membranes, and were released in cytosol exclusively as naked capsids, exactly as
      in intact cells. This is most consistent with the view that the virus escapes by
      crossing the two nuclear membranes rather than through nuclear pores.
      Unexpectedly, nuclei isolated at the nonpermissive temperature from cells
      infected with a U(L)26 thermosensitive protease mutant (V701) supported capsid
      egress. Although electron microscopy, biochemical, and PCR analyses hinted at a
      likely reconstitution of capsid maturation, DNA encapsidation could not be
      confirmed by a traditional SQ test. This assay should prove very useful for
      identification of the molecular players involved in HSV-1 nuclear egress.

PMID- 16973579
TI  - Proteasome inhibition reveals that a functional preintegration complex
      intermediate can be generated during restriction by diverse TRIM5 proteins.
AB  - The primate TRIM5 proteins constitute a class of restriction factors that prevent
      host cell infection by retroviruses from different species. The TRIM5 proteins
      act early after virion entry and prevent viral reverse transcription products
      from accumulating. We recently found that proteasome inhibitors altered the
      rhesus monkey TRIM5alpha restriction of human immunodeficiency virus type 1 (HIV
      1), allowing reverse transcription products to accumulate even though viral
      infection remained blocked. To assess whether sensitivity to proteasome
      inhibitors was a common feature of primate TRIM5 proteins, we conducted a similar
      analysis of restriction mediated by owl monkey TRIM-cyclophilin A (CypA) or human
      TRIM5alpha. Similar to rhesus monkey TRIM5alpha restriction, proteasome
      inhibition prevented owl monkey TRIM-CypA restriction of HIV-1 reverse
      transcription, even though HIV-1 infection and the output of 2-LTR circles
      remained impaired. Likewise, proteasome inhibition alleviated human TRIM5alpha
      restriction of N-tropic murine leukemia virus reverse transcription. Finally, HIV
      1 reverse transcription products escaping rhesus TRIM5alpha restriction by
      proteasome inhibition were fully competent for integration in vitro,
      demonstrating that TRIM5alpha likely prevents the viral cDNA from accessing
      chromosomal target DNA. Collectively, these data indicate that the diverse TRIM5
      proteins inhibit retroviral infection in multiple ways and that inhibition of
      reverse transcription products is not necessary for TRIM5-mediated restriction of
      retroviral infection.

PMID- 16973580
TI  - Cellular target genes of Epstein-Barr virus nuclear antigen 2.
AB  - Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA-2) is a key determinant in the
      EBV-driven B-cell growth transformation process. By activating an array of viral
      and cellular target genes, EBNA-2 initiates a cascade of events which ultimately
      cause cell cycle entry and the proliferation of the infected B cell. In order to
      identify cellular target genes that respond to EBNA-2 in the absence of other
      viral factors, we have performed a comprehensive search for EBNA-2 target genes
      in two EBV-negative B-cell lines. This screen identified 311 EBNA-2-induced and
      239 EBNA-2-repressed genes that were significantly regulated in either one or
      both cell lines. The activation of most of these genes had not previously been
      attributed to EBNA-2 function and will be relevant for the identification of EBNA
      2-specific contributions to EBV-associated malignancies. The diverse spectrum of
      EBNA-2 target genes described in this study reflects the broad spectrum of EBNA-2
      functions involved in virus-host interactions, including cell signaling
      molecules, adapters, genes involved in cell cycle regulation, and chemokines.

PMID- 16973581
TI  - Persistent high frequencies of varicella-zoster virus ORF4 protein-specific CD4+
      T cells after primary infection.
AB  - Open reading frame 4 (ORF4) of varicella-zoster virus (VZV) encodes an immediate
      early protein that is believed to be important for viral infectivity and
      establishing latency. Evidence suggests that VZV-specific T cells are crucial in
      the control of viral replication, but there are no data addressing the existence
      of potential ORF4 protein-specific CD4+ T cells. We tested the hypothesis that
      VZV ORF4 protein-specific CD4+ T cells could be identified and characterized
      within the peripheral blood of healthy immune donors following primary infection.
      Gamma interferon (IFN-gamma) immunosorbent assays were used to screen peripheral
      blood mononuclear cells obtained from healthy seropositive donors for responses
      to overlapping ORF4 peptides, viral lysate, and live vaccine. High frequencies of
      ORF4 protein-specific T cells were detected ex vivo in individuals up to 52 years
      after primary infection. Several immunogenic regions of the ORF4 protein were
      identified, including a commonly recognized epitope which was restricted through
      HLA-DRB1*07. Total ORF4 protein-specific responses comprised 19.7% and 20.7% of
      the total lysate and vaccine responses, respectively, and were dominated by CD4+
      T cells. Indeed, CD4+ T cells were found to dominate the overall virus-specific
      IFN-gamma cellular immune response both ex vivo and after expansion in vitro. In
      summary, we have identified an ORF4 protein as a novel target antigen for
      persistent VZV-specific CD4+ T cells, with implications for disease pathogenesis
      and future vaccine development.

PMID- 16973582
TI  - Induction of human immunodeficiency virus type 1 (HIV-1)-specific T-cell
      responses in HIV vaccine trial participants who subsequently acquire HIV-1
      infection.
AB  - Candidate human immunodeficiency virus type 1 (HIV-1) vaccines designed to elicit
      T-cell immunity in HIV-1-uninfected persons are under investigation in phase I to
      III clinical trials. Little is known about how these vaccines impact the
      immunologic response postinfection in persons who break through despite
      vaccination. Here, we describe the first comprehensive characterization of HIV
      specific T-cell immunity in vaccine study participants following breakthrough HIV
      1 infection in comparison to 16 nonvaccinated subjects with primary HIV-1
      infection. Whereas none of the 16 breakthrough infections possessed vaccine
      induced HIV-1-specific T-cell responses preinfection, 85% of vaccinees and 86% of
      nonvaccinees with primary HIV-1 infection developed HIV-specific T-cell responses
      postinfection. Breakthrough subjects' T cells recognized 43 unique HIV-1 T-cell
      epitopes, of which 8 are newly described, and 25% were present in the vaccine.
      The frequencies of gamma interferon (IFN-gamma)-secreting cells recognizing
      epitopes within gene products that were and were not encoded by the vaccine were
      not different (P = 0.64), which suggests that responses were not anamnestic.
      Epitopes within Nef and Gag proteins were the most commonly recognized in both
      vaccinated and nonvaccinated infected subjects. One individual controlled viral
      replication without antiretroviral therapy and, notably, mounted a novel HIV
      specific HLA-C14-restricted Gag LYNTVATL-specific T-cell response.
      Longitudinally, HIV-specific T cells in this individual were able to secrete IFN
      gamma and tumor necrosis factor alpha, as well as proliferate and degranulate in
      response to their cognate antigenic peptides up to 5 years postinfection. In
      conclusion, a vaccinee's ability to mount an HIV-specific T-cell response
      postinfection is not compromised by previous immunization, since the CD8+ T-cell
      responses postinfection are similar to those seen in vaccine-naive individuals.
      Finding an individual who is controlling infection highlights the importance of
      comprehensive studies of breakthrough infections in vaccine trials to determine
      whether host genetics/immune responses and/or viral characteristics are
      responsible for controlling viral replication.

PMID- 16973583
TI  - Major histocompatibility complex class II molecules promote human
      immunodeficiency virus type 1 assembly and budding to late
      endosomal/multivesicular body compartments.
AB  - Human immunodeficiency virus type 1 (HIV-1) assembly, budding, and release occur
      mostly at the plasma membrane in T lymphocytes as well as in established
      nonlymphoid cell lines, while in macrophages these processes occur primarily in
      intracellular compartments that harbor late endosomal/multivesicular body
      (LE/MVB) markers, including human leukocyte antigen DR (HLA-DR). Major
      histocompatibility complex class II molecules (MHC-II), which are expressed in
      macrophages and activated T cells, have been previously reported to induce the
      formation of multilaminar and multivesicular endocytic MHC-II-like structures
      analogous to MVB upon their expression in HEK 293 cells. Here, we have examined
      the role of MHC-II in HIV-1 Gag targeting as well as in virus assembly and
      release. Expression of HLA-DR in nonlymphoid cell lines induced a relocation of
      Gag to intracellular compartments that harbored LE/MVB markers and increased the
      accumulation of viral particles assembling intracellularly. Consequently, viral
      production and release from the cell surface was found to be substantially
      decreased in HLA-DR-expressing cells. This process was specific, since it was not
      observed with HLA-DR molecules lacking their cytoplasmic tails, nor with
      structurally related but functionally distinct MHC-II molecules such as HLA-DM or
      HLA-DO. Importantly, virus released intracellularly in HLA-DR-expressing cells
      retained infectivity. Overall, these results suggest a role of MHC-II molecules
      in promoting HIV-1 assembly and budding to LE/MVB and raise the possibility that
      this activity might be part of a normal pathway of virus production in cell types
      physiologically expressing MHC-II molecules, such as macrophages.

PMID- 16973584
TI  - Specificity of the VP1 GH loop of Foot-and-Mouth Disease virus for alphav
      integrins.
AB  - Foot-and-mouth disease virus (FMDV) can use a number of integrins as receptors to
      initiate infection. Attachment to the integrin is mediated by a highly conserved
      arginine-glycine-aspartic acid (RGD) tripeptide located on the GH loop of VP1.
      Other residues of this loop are also conserved and may contribute to integrin
      binding. In this study we have used a 17-mer peptide, whose sequence corresponds
      to the GH loop of VP1 of type O FMDV, as a competitor of integrin-mediated virus
      binding and infection. Alanine substitution through this peptide identified the
      leucines at the first and fourth positions following RGD (RGD+1 and RGD+4 sites)
      as key for inhibition of virus binding and infection mediated by alphavbeta6 or
      alphavbeta8 but not for inhibition of virus binding to alphavbeta3. We also show
      that FMDV peptides containing either methionine or arginine at the RGD+1 site,
      which reflects the natural sequence variation seen across the FMDV serotypes, are
      effective inhibitors for alphavbeta6. In contrast, although RGDM-containing
      peptides were effective for alphavbeta8, RGDR-containing peptides were not. These
      observations were confirmed by showing that a virus containing an RGDR motif uses
      alphavbeta8 less efficiently than alphavbeta6 as a receptor for infection.
      Finally, evidence is presented that shows alphavbeta3 to be a poor receptor for
      infection by type O FMDV. Taken together, our data suggest that the integrin
      binding loop of FMDV has most likely evolved for binding to alphavbeta6 with a
      higher affinity than to alphavbeta3 and alphavbeta8.

PMID- 16973585
TI  - Structural requirements for gp80 independence of human herpesvirus 8 interleukin
      6 (vIL-6) and evidence for gp80 stabilization of gp130 signaling complexes
      induced by vIL-6.
AB  - Human herpesvirus 8 interleukin-6 (vIL-6) displays 25% amino acid identity with
      human IL-6 (hIL-6) and shares an overall four-helix-bundle structure and gp130
      mediated STAT/mitogen-activated protein kinase signaling with its cellular
      counterpart. However, vIL-6 is distinct in that it can signal through gp130
      alone, in the absence of the nonsignaling gp80 alpha-subunit of the IL-6
      receptor. To investigate the structural requirements for gp80 independence of vIL
      6, a series of expression vectors encoding vIL-6/hIL-6 chimeric and site-mutated
      IL-6 proteins was generated. The replacement of hIL-6 residues with three vIL-6
      specific tryptophans implicated in gp80 independence from crystallographic
      studies or the A and C helices containing these residues did not confer gp80
      independence to hIL-6. The N- and C-terminal regions of vIL-6 could be
      substituted with hIL-6 sequences with the retention of gp80-independent
      signaling, but substitutions of other regions of vIL-6 (helix A, A/B loop, helix
      B, helix C, and proximal half of helix D) with equivalent sequences of hIL-6
      abolished gp80 independence. Interestingly, the B helix of vIL-6 was absolutely
      required for gp80 independence, despite the fact that this region contains no
      receptor-binding residues. Point mutational analysis of helix C, which contains
      residues involved in physical and functional interactions with gp130 domains 2
      and 3 (cytokine-binding homology region), identified a variant, VI120EE, that was
      able to signal and dimerize gp130 only in the presence of gp80. gp80 was also
      found to stabilize gp130:g130 dimers induced by a distal D helix variant of vIL-6
      that was nonetheless able to signal independently of gp80. Together, our data
      reveal the crucial importance of overall vIL-6 structure and conformation for
      gp80-independent signaling and provide functional and physical evidence of the
      stabilization of vIL-6-induced gp130 signaling complexes by gp80.

PMID- 16973586
TI  - Vaccinia virus G9 protein is an essential component of the poxvirus entry-fusion
      complex.
AB  - The vaccinia virus G9R gene (VACWR087) encodes a protein of 340 amino acids with
      the following structural features that are conserved in all poxviruses: a site
      for N-terminal myristoylation, 14 cysteines, and a C-terminal transmembrane
      domain. Previous studies showed that G9 is one of eight proteins associated in a
      putative entry-fusion complex. Our attempt to isolate a mutant without the G9R
      gene was unsuccessful, suggesting that it is essential for virus replication. To
      further investigate its role, we constructed a recombinant vaccinia virus in
      which G9R is regulated by addition of an inducer. Induced G9 protein was
      associated with mature infectious virions and could be labeled with a membrane
      impermeant biotinylation reagent, indicating surface exposure. Omission of
      inducer reduced the infectious-virus yield by about 1.5 logs; nevertheless, all
      stages of virus morphogenesis appeared normal and extracellular virions were
      present on the cell surface. Purified virions assembled without inducer had a
      specific infectivity of less than 5% of the normal level and a comparably small
      amount of G9, whereas their overall polypeptide composition, including other
      components of the entry-fusion complex, was similar to that of virions made in
      the presence of inducer or of wild-type virions. G9-deficient virions bound to
      cells, but penetration of cores into the cytoplasm and early viral RNA synthesis
      were barely detected, and cell-cell fusion was not triggered by low pH. Of the
      identified components of the multiprotein complex, G9 is the sixth that has been
      shown to be required for entry and membrane fusion.

PMID- 16973587
TI  - The 37/67-kilodalton laminin receptor is a receptor for adeno-associated virus
      serotypes 8, 2, 3, and 9.
AB  - Adeno-associated virus serotype 8 (AAV8) is currently emerging as a powerful gene
      transfer vector, owing to its capability to efficiently transduce many different
      tissues in vivo. While this is believed to be in part due to its ability to
      uncoat more readily than other AAV serotypes such as AAV2, understanding all the
      processes behind AAV8 transduction is important for its application and optimal
      use in human gene therapy. Here, we provide the first report of a cellular
      receptor for AAV8, the 37/67-kDa laminin receptor (LamR). We document binding of
      LamR to AAV8 capsid proteins and intact virions in vitro and demonstrate its
      contribution to AAV8 transduction of cultured cells and mouse liver in vivo. We
      also show that LamR plays a role in transduction by three other closely related
      serotypes (AAV2, -3, and -9). Sequence and deletion analysis allowed us to map
      LamR binding to two protein subdomains predicted to be exposed on the AAV capsid
      exterior. Use of LamR, which is constitutively expressed in many clinically
      relevant tissues and is overexpressed in numerous cancers, provides a molecular
      explanation for AAV8's broad tissue tropism. Along with its robust transduction
      efficiency, our findings support the continued development of AAV8-based vectors
      for clinical applications in humans, especially for tumor gene therapy.

PMID- 16973588
TI  - Inhibition of hendra virus fusion.
AB  - Hendra virus (HeV) is a recently identified paramyxovirus that is fatal in humans
      and could be used as an agent of bioterrorism. The HeV receptor-binding protein
      (G) is required in order for the fusion protein (F) to mediate fusion, and
      analysis of the triggering/activation of HeV F by G should lead to strategies for
      interfering with this key step in viral entry. HeV F, once triggered by the
      receptor-bound G, by analogy with other paramyxovirus F proteins, undergoes
      multistep conformational changes leading to a six-helix bundle (6HB) structure
      that accomplishes fusion of the viral and cellular membranes. The ectodomain of
      paramyxovirus F proteins contains two conserved heptad repeat regions (HRN and
      HRC) near the fusion peptide and the transmembrane domains, respectively.
      Peptides derived from the HRN and HRC regions of F are proposed to inhibit fusion
      by preventing F, after the initial triggering step, from forming the 6HB
      structure that is required for fusion. HeV peptides have previously been found to
      be effective at inhibiting HeV fusion. However, we found that a human
      parainfluenza virus 3 F-peptide is more effective at inhibiting HeV fusion than
      the comparable HeV-derived peptide.

PMID- 16973589
TI  - A full-genome phylogenetic analysis of varicella-zoster virus reveals a novel
      origin of replication-based genotyping scheme and evidence of recombination
      between major circulating clades.
AB  - Varicella-zoster virus (VZV) is a remarkably stable virus that until recently was
      thought to exhibit near-universal genetic homogeneity among circulating wild-type
      strains. In recent years, the expanding knowledge of VZV genetics has led to a
      number of groups proposing sequence-based typing schemes, but no study has yet
      examined the relationships between VZV genotypes at a full-genome level. A
      central hypothesis of this study is that VZV has coevolved with humankind. In
      this study, 11 additional full VZV genomic sequences are presented, bringing the
      current number of complete genomic sequences publicly available to 18. The full
      genome alignment contained strains representing four distinct clades, but the
      possibility exists that a fifth clade comprised of African and Asian-like
      isolates was not represented. A consolidated VZV genotyping scheme employing the
      origin-associated region between reiteration region R4 and open reading frames
      (ORFs) 63 and 70 is described, one which accurately categorizes strains into one
      of four clades related to the geographic origin of the isolates. The full-genome
      alignment also provided evidence for recombination having occurred between the
      major circulating VZV clades. One Canadian clinical isolate was primarily Asian
      like in origin, with most of the genome showing strong sequence identity to the
      Japanese-like clade B, with the exceptions being two putative recombination
      regions, located in ORFs 14 to 17 and ORFs 22 to 26, which showed clear
      similarity to the European/North American clade A. The very low rate of single
      nucleotide polymorphisms scattered across the genome made full-genome sequencing
      the only definitive method for identifying specific VZV recombination events.

PMID- 16973590
TI  - Rapid viral decay in simian immunodeficiency virus-infected macaques receiving
      quadruple antiretroviral therapy.
AB  - The viral dynamics in human immunodeficiency virus type 1 (HIV-1) infection have
      been studied extensively using mathematical modeling, but data from other primate
      lentivirus systems are scarce. This study was initiated to increase the
      understanding of the differences and similarities between the different primate
      lentiviruses. Four cynomolgus macaques were infected with SIVmac251. Six months
      after infection the monkeys received a 7-day course of subcutaneous, quadruple
      antiretroviral therapy with zidovudine, lamivudine, tenofovir, and ritonavir
      boosted lopinavir. Plasma virus levels were determined before therapy, daily
      during the first 10 days of therapy, and after 14 days using a sensitive
      commercial reverse transcriptase assay. All four monkeys showed a rapid and
      uniform decline in plasma virus load between day 1 and day 4 of treatment (first
      phase decay). Two mathematical models, a piecewise linear regression analysis and
      a nonlinear model, were used to estimate the rate of viral decay in plasma and
      gave similar results. The mean half-life for plasma virus was 0.47 days (range,
      0.37 to 0.50) and reflects the underlying decline of virus-producing CD4+
      lymphocytes. This is the fastest primate lentivirus decay described hitherto. The
      rapid decay may be due to the high antiviral potency of the therapy or to
      intrinsic differences between simian immunodeficiency virus (SIV) infection in
      macaques and HIV-1 infection in humans.

PMID- 16973591
TI  - Role of RNA structure and RNA binding activity of foot-and-mouth disease virus 3C
      protein in VPg uridylylation and virus replication.
AB  - The uridylylation of the VPg peptide primer is the first stage in the replication
      of picornavirus RNA. This process can be achieved in vitro using purified
      components, including 3B (VPg) with the RNA dependent RNA polymerase (3Dpol), the
      precursor 3CD, and an RNA template containing the cre/bus. We show that certain
      RNA sequences within the foot-and-mouth disease virus (FMDV) 5' untranslated
      region but outside of the cre/bus can enhance VPg uridylylation activity.
      Furthermore, we have shown that the FMDV 3C protein alone can substitute for 3CD,
      albeit less efficiently. In addition, the VPg precursors, 3B(3)3C and 3B(123)3C,
      can function as substrates for uridylylation in the absence of added 3C or 3CD.
      Residues within the FMDV 3C protein involved in interaction with the cre/bus RNA
      have been identified and are located on the face of the protein opposite from the
      catalytic site. These residues within 3C are also essential for VPg uridylylation
      activity and efficient virus replication.

PMID- 16973592
TI  - Human T-cell lymphotropic virus type 3: complete nucleotide sequence and
      characterization of the human tax3 protein.
AB  - We and others have recently uncovered the existence of human T-cell lymphotropic
      virus type 3 (HTLV-3), the third member of the HTLV family. We have now sequenced
      the full-length HTLV-3Pyl43 provirus. As expected, HTLV-3Pyl43 contains open
      reading frames corresponding to the gag, pol, env, tax, and rex genes.
      Interestingly, its long terminal repeat (LTR) includes only two Tax-responsive
      elements, as is the case for type 3 simian T-cell lymphotropic viruses (STLV-3).
      Phylogenetic analyses reveal that HTLV-3Pyl43 is closely related to central
      African STLV-3. Unexpectedly, the proximal pX region of HTLV-3Pyl43 lacks 366 bp
      compared to its STLV-3 counterpart. Because of this deletion, the previously
      described RorfII sequence is lacking. At the amino acid level, Tax3Pyl43 displays
      strong similarities with HTLV-1 Tax, including the sequence of a PDZ class I
      binding motif. In transient-transfection assays, Tax3Pyl43 activates the
      transcriptions from HTLV-3, HTLV-1, and HTLV-2 LTRs. Mutational analysis
      indicates that two functional domains (M22 and M47) important for transactivation
      through the CREB/ATF or NF-kappaB pathway are similar but not identical in Tax1
      and Tax3Pyl43. We also show that Tax3Pyl43 transactivates the human interleukin-8
      and Bcl-XL promoters through the induction of the NF-kappaB pathway. On the other
      hand, Tax3Pyl43 represses the transcriptional activity of the p53 tumor
      suppressor protein as well as the c-Myb promoter. Altogether, these results
      demonstrate that although HTLV-3 and HTLV-1 have only 60% identity, Tax3Pyl43 is
      functionally closely related to the transforming protein Tax1 and suggest that
      HTLV-3, like HTLV-1, might be pathogenic in vivo.

PMID- 16973593
TI  - Mobilization of full-length Semliki Forest virus replicon by retrovirus
      particles.
AB  - Conciliating biosafety with efficient gene transfer remains a constant concern in
      the development of retroviral vectors. Semliki Forest virus (SFV) replicons allow
      important retroviral vector production with interesting features. It is
      noteworthy that retroviruses have the ability to package Psi+ and, to some
      extent, Psi- cellular RNAs. Therefore, it was important to study the retroviral
      transfer of highly abundant SFV genomes expressing retroviral proteins. Here, we
      show that full-length SFV-vector replicons, with or without Psi, are efficiently
      packaged into retrovirus particles. Mechanistically, our data suggest that SFV
      packaging is the sum of its retroviral nucleocapsid-dependent recruitment
      together with a passive hijacking of membrane-anchored SFV replicon. A direct
      consequence of this phenomenon is the formation of particles harboring autonomous
      replicative abilities and contaminating vector preparations. Importantly, we
      confirm that retroviral SFV mobilization is not an exclusive feature of murine
      gamma retroviruses, since it is also observed using lentivectors.

PMID- 16973594
TI  - Proteolytic activation of influenza viruses by serine proteases TMPRSS2 and HAT
      from human airway epithelium.
AB  - Host cell proteases that cleave the hemagglutinin (HA) of influenza viruses in
      the human respiratory tract are still not identified. Here we cloned two human
      type II transmembrane serine proteases with known airway localization, TMPRSS2
      and HAT, into mammalian expression vector. Cotransfection of mammalian cells with
      plasmids encoding HA and either protease resulted in HA cleavage in situ.
      Transient expression of either protease in MDCK cells enabled multicycle
      replication of influenza viruses in these cells in the absence of exogenous
      trypsin. These data suggest that TMPRSS2 and HAT are candidates for proteolytic
      activation of influenza viruses in vivo.

PMID- 16973595
TI  - Regulation of the transcription and replication cycle of human cytomegalovirus is
      insensitive to genetic elimination of the cognate NF-kappaB binding sites in the
      enhancer.
AB  - The role of NF-kappaB in regulating human cytomegalovirus (HCMV) replication and
      gene transcription remains controversial. Multiple, functional NF-kappaB response
      elements exist in the major immediate-early promoter (MIEP) enhancer of HCMV,
      suggesting a possible requirement for this transcription factor in lytic viral
      replication. Here we demonstrate by generating and analyzing HCMVs with
      alterations in the MIEP-enhancer that, although this region is essential for HCMV
      growth, none of the four NF-kappaB response elements contained within the
      enhancer are required for MIE gene expression or HCMV replication in multiple
      cell types. These data reveal the robustness of the regulatory network
      controlling the MIEP enhancer.

PMID- 16973596
TI  - Evaluation of the lytic origins of replication of Kaposi's sarcoma-associated
      virus/human herpesvirus 8 in the context of the viral genome.
AB  - The lytic origins of DNA replication for human herpesvirus 8 (HHV8), oriLyt-L and
      oriLyt-R, are located between open reading frames K4.2 and K5 and ORF69 and
      vFLIP, respectively. These lytic origins were elucidated using a transient
      replication assay. Although this assay is a powerful tool for identifying many
      herpesvirus lytic origins, it is limited in its ability to evaluate the activity
      of replication origins in the context of the viral genome. To this end, we
      investigated the ability of a recombinant HHV8 bacterial artificial chromosome
      (BAC) to replicate in the absence of oriLyt-R, oriLyt-L, or both oriLyt regions.
      We generated the HHV8 BAC recombinants (BAC36-DeltaOri-R, BAC36-DeltaOri-L, and
      BAC36-DeltaOri-RL), which removed one or all of the identified lytic origins. An
      evaluation of these recombinant BACs revealed that oriLyt-L was sufficient to
      propagate the viral genome, whereas oriLyt-R alone failed to direct the
      amplification of viral DNA.

PMID- 16973597
TI  - Identification of a 709-amino-acid internal nonessential region within the
      essential conserved tegument protein (p)UL36 of pseudorabies virus.
AB  - Tegument proteins homologous to the essential herpes simplex virus type 1 UL36
      gene product (p)UL36 are conserved throughout the Herpesviridae and constitute
      the largest herpesvirus-encoded proteins. So far, only limited information is
      available on their functions, which include complex formation with the (p)UL37
      homologs via an N-terminal domain and a deubiquitinating activity in the extreme
      N terminus. For further analysis we constructed deletion mutants lacking 437,
      784, 926, 1,046, 1,217, or 1,557 amino acids (aa) from the C terminus. While none
      of them supported replication of a pseudorabies virus (PrV) UL36 deletion mutant,
      a mutant polypeptide with an internal deletion from aa 2087 to 2795, which
      comprises a proline/alanine-rich region, fully complemented the lethal
      replication defect. Thus, our data indicate that the extreme C terminus of
      (p)UL36 fulfills an essential role in PrV replication, while a large internal
      portion of the C-terminal half of the protein is dispensable for replication in
      cell culture.

PMID- 16973598
TI  - Induction of cell-cell fusion from without by human herpesvirus 6B.
AB  - Human herpesvirus (HHV) 6A induce fusion from without (FFWO), whereas HHV-6B is
      believed to be ineffective in this process. Here, we demonstrate that HHV-6B
      induces rapid fusion in both epithelial cells and lymphocytes. The fusion was
      identified 1 h postinfection, could be inhibited by antibodies to HHV-6B gH and
      to the cellular receptor CD46, and was dependent on virus titer but independent
      of de novo protein synthesis and UV inactivation of the virus. Comparisons
      indicate that HHV-6A is only 10-fold more effective in inducing FFWO than HHV-6B.
      These data demonstrate that HHV-6B can induce FFWO in epithelial cells and
      lymphocytes.

PMID- 16973599
TI  - Receptor-triggered but alkylation-arrested env of murine leukemia virus reveals
      the transmembrane subunit in a prehairpin conformation.
AB  - A central feature of the prevailing model for retrovirus fusion is conversion of
      the transmembrane (TM) subunit from a prehairpin to a hairpin-like structure. The
      fusion inhibition of many retroviruses, except murine leukemia virus (MLV), with
      peptides corresponding to interacting regions in the hairpin supports the model.
      MLV fusion is controlled by isomerization of the intersubunit disulfide in Env.
      We show here that TM peptides bind to MLV Env that has been arrested at an
      intermediate stage of activation by alkylation of the isomerization-active thiol
      in the surface subunit. This inhibits fusion rescue by dithiothreitol-mediated
      reduction of the surface protein-TM disulfide.

PMID- 16973600
TI  - Transcriptional profiling of the protein phosphatase 2C family in yeast provides
      insights into the unique functional roles of Ptc1.
AB  - Type 2C protein phosphatases are encoded in Saccharomyces cerevisiae by several
      related genes (PTC1-5 and PTC7). To gain insight into the functions attributable
      to specific members of this gene family, we have investigated the transcriptional
      profiles of ptc1-5 mutants. Two main patterns were obtained as follows: the one
      generated by the ptc1 mutation and the one resulting from the lack of Ptc2-5.
      ptc4 and ptc5 profiles were quite similar, whereas that of ptc2 was less related
      to this group. Mutation of PTC1 resulted in increased expression of numerous
      genes that are also induced by cell wall damage, such as YKL161c, SED1, or CRH1,
      as well as in higher amounts of active Slt2 mitogen-activated protein kinase,
      indicating that lack of the phosphatase activates the cell wall integrity
      pathway. ptc1 cells were even more sensitive than slt2 mutants to a number of
      cell wall-damaging agents, and both mutations had additive effects. The
      sensitivity of ptc1 cells was not dependent on Hog1. Besides these phenotypes, we
      observed that calcineurin was hyperactivated in ptc1 cells, which were also
      highly sensitive to calcium ions, heavy metals, and alkaline pH, and exhibited a
      random haploid budding pattern. Remarkably, many of these traits are found in
      certain mutants with impaired vacuolar function. As ptc1 cells also display
      fragmented vacuoles, we hypothesized that lack of Ptc1 would primarily cause
      vacuolar malfunction, from which other phenotypes would derive. In agreement with
      this scenario, overexpression of VPS73, a gene of unknown function involved in
      vacuolar protein sorting, largely rescues not only vacuolar fragmentation but
      also sensitivity to cell wall damage, high calcium, alkaline pH, as well as other
      ptc1-specific phenotypes.

PMID- 16973601
TI  - Integrin beta4 regulates migratory behavior of keratinocytes by determining
      laminin-332 organization.
AB  - Whether alpha6beta4 integrin regulates migration remains controversial. beta4
      integrin-deficient (JEB) keratinocytes display aberrant migration in that they
      move in circles, a behavior that mirrors the circular arrays of laminin (LM)-332
      in their matrix. In contrast, wild-type keratinocytes and JEB keratinocytes,
      induced to express beta4 integrin, assemble laminin-332 in linear tracks over
      which they migrate. Moreover, laminin-332-dependent migration of JEB
      keratinocytes along linear tracks is restored when cells are plated on wild-type
      keratinocyte matrix, whereas wild-type keratinocytes show rotation over circular
      arrays of laminn-332 in JEB keratinocyte matrix. The activities of Rac1 and the
      actin cytoskeleton-severing protein cofilin are low in JEB keratinocytes compared
      with wild-type cells but are rescued following expression of wild-type beta4
      integrin in JEB cells. Additionally, in wild-type keratinocytes Rac1 is complexed
      with alpha6beta4 integrin. Moreover, Rac1 or cofilin inactivation induces wild
      type keratinocytes to move in circles over rings of laminin-332 in their matrix.
      Together these data indicate that laminin-332 matrix organization is determined
      by the alpha6beta4 integrin/actin cytoskeleton via Rac1/cofilin signaling.
      Furthermore, our results imply that the organizational state of laminin-332 is a
      key determinant of the motility behavior of keratinocytes, an essential element
      of skin wound healing and the successful invasion of epidermal-derived tumor
      cells.

PMID- 16973602
TI  - Heat shock proteins 70 and 90 inhibit early stages of amyloid beta-(1-42)
      aggregation in vitro.
AB  - Alzheimer disease is a neurological disorder that is characterized by the
      presence of fibrils and oligomers composed of the amyloid beta (Abeta) peptide.
      In models of Alzheimer disease, overexpression of molecular chaperones,
      specifically heat shock protein 70 (Hsp70), suppresses phenotypes related to
      Abeta aggregation. These observations led to the hypothesis that chaperones might
      interact with Abeta and block self-association. However, although biochemical
      evidence to support this model has been collected in other neurodegenerative
      systems, the interaction between chaperones and Abeta has not been similarly
      explored. Here, we examine the effects of Hsp70/40 and Hsp90 on Abeta aggregation
      in vitro. We found that recombinant Hsp70/40 and Hsp90 block Abeta self-assembly
      and that these chaperones are effective at substoichiometric concentrations
      (approximately 1:50). The anti-aggregation activity of Hsp70 can be inhibited by
      a nonhydrolyzable nucleotide analog and encouraged by pharmacological stimulation
      of its ATPase activity. Finally, we were interested in discerning what type of
      amyloid structures can be acted upon by these chaperones. To address this
      question, we added Hsp70/40 and Hsp90 to pre-formed oligomers and fibrils. Based
      on thioflavin T reactivity, the combination of Hsp70/40 and Hsp90 caused
      structural changes in oligomers but had little effect on fibrils. These results
      suggest that if these chaperones are present in the same cellular compartment in
      which Abeta is produced, Hsp70/40 and Hsp90 may suppress the early stages of self
      assembly. Thus, these results are consistent with a model in which
      pharmacological activation of chaperones might have a favorable therapeutic
      effect on Alzheimer disease.

PMID- 16973603
TI  - Critical role of the proline-rich region in Huntingtin for aggregation and
      cytotoxicity in yeast.
AB  - Nine neurodegenerative diseases, such as Huntington, are caused by a
      polyglutamine (poly(Q)) expansion in otherwise unrelated proteins. Although
      poly(Q) expansion causes aggregation of the affected proteins, the protein
      context might determine the selective neuronal vulnerability found in each
      disease. Here we have report that, although expression of Huntingtin derivatives
      with a pathological poly(Q) expansion are innocuous in yeast, deletion of the
      flanking proline-rich region alters the shape and number of poly(Q) inclusions
      and unmasks toxic properties. Strikingly, deletion of Hsp104 increases the size
      of inclusions formed by expanded poly(Q) lacking the proline-rich region and
      abolishes toxicity. Overexpression of the chaperones Hsp104 or Hsp70 rescues
      growth defects in affected cells without resolving inclusions. However,
      aggregates formed by nontoxic Huntingtin derivatives or by toxic derivatives
      cured by chaperones are physically distinct from aggregates formed by toxic
      proteins. This study identifies the proline-rich region in Huntingtin as a
      profound cis-acting modulator of expanded poly(Q) toxicity and distinguishes
      between aggregates of toxic or non-toxic proteins.

PMID- 16973604
TI  - An archaeal peptidase assembles into two different quaternary structures: A
      tetrahedron and a giant octahedron.
AB  - Cellular proteolysis involves large oligomeric peptidases that play key roles in
      the regulation of many cellular processes. The cobalt-activated peptidase TET1
      from the hyperthermophilic Archaea Pyrococcus horikoshii (PhTET1) was found to
      assemble as a 12-subunit tetrahedron and as a 24-subunit octahedral particle.
      Both quaternary structures were solved by combining x-ray crystallography and
      cryoelectron microscopy data. The internal organization of the PhTET1 particles
      reveals highly self-compartmentalized systems made of networks of access channels
      extended by vast catalytic chambers. The two edifices display aminopeptidase
      activity, and their organizations indicate substrate navigation mechanisms
      different from those described in other large peptidase complexes. Compared with
      the tetrahedron, the octahedron forms a more expanded hollow structure,
      representing a new type of giant peptidase complex. PhTET1 assembles into two
      different quaternary structures because of quasi-equivalent contacts that
      previously have only been identified in viral capsids.

PMID- 16973605
TI  - Functional analysis of CbpA, a DnaJ homolog and nucleoid-associated DNA-binding
      protein.
AB  - DnaK/Hsp70 proteins are universally conserved ATP-dependent molecular chaperones
      that help proteins adopt and maintain their native conformations. DnaJ/Hsp40 and
      GrpE are co-chaperones that assist DnaK. CbpA is an Escherichia coli DnaJ
      homolog. It acts as a multicopy suppressor for dnaJ mutations and functions in
      vitro in combination with DnaK and GrpE in protein remodeling reactions. CbpA
      binds nonspecifically to DNA with preference for curved DNA and is a nucleoid
      associated protein. The DNA binding and co-chaperone activities of CbpA are
      modulated by CbpM, a small protein that binds specifically to CbpA. To identify
      the regions of CbpA involved in the interaction of CbpA with CbpM and those
      involved in DNA binding, we constructed and characterized deletion and
      substitution mutants of CbpA. We discovered that CbpA interacted with CbpM
      through its N-terminal J-domain. We found that the region C-terminal to the J
      domain was required for DNA binding. Moreover, we found that the CbpM
      interaction, DNA binding, and co-chaperone activities were separable; some
      mutants were proficient in some functions and defective in others.

PMID- 16973606
TI  - Identification of a filamin docking site on PTP-PEST.
AB  - PTP-PEST is a cytoplasmic protein-tyrosine phosphatase (PTP) implicated in the
      regulation of biological processes such as cell motility, cytokinesis, focal
      adhesion disassembly, and lymphocyte activation. Using a proteomics approach,
      filamin-A was identified as a novel interacting protein that bound to GST-PTP
      PEST. This interaction was confirmed in vitro and in cells by
      coimmunoprecipitation. The site of filamin interaction on PTP-PEST was mapped to
      the fourth proline-rich region (Pro4). PTP-PEST has previously been implicated in
      the regulation of cytokinesis. In further support of this finding, expression of
      PTP-PEST in HeLa cells resulted in the formation of multinucleated cells. A PTP
      PEST mutant lacking Pro4 and unable to bind filamin-A failed to induce the
      multinucleated phenotype. Further, depletion of filamin-A in HeLa cells was found
      to reduce the PTP-PEST-dependent multinucleation phenotype. Hence, we conclude
      that the interaction of PTP-PEST with filamin-A may function in the control of
      cytokinesis in mammalian cells.

PMID- 16973607
TI  - Ryanodine receptors in liver.
AB  - The ryanodine receptor has been mainly regarded as the Ca2+ release channel from
      sarcoplasmic reticulum controlling skeletal and cardiac muscle contraction.
      However, many studies have shown that it is widely expressed, with functions not
      restricted to muscular contraction. This study examined whether ryanodine
      receptor plays a role in calcium signaling in the liver. RT-PCR analysis of
      isolated hepatocytes showed expression of a truncated type 1 ryanodine receptor,
      but no type 2 or type 3 message was detected. We also detected binding sites for
      [3H]ryanodine in the microsomal cellular fraction and in permeabilized
      hepatocytes. This binding was displaced by caffeine and dantrolene, but not by
      ruthenium red, heparin or cyclic ADP-Ribose. Ryanodine, by itself, did not
      trigger Ca2+ oscillations in either primary cultured hepatocytes or hepatocytes
      within the intact perfused rat liver. In both preparations, however, ryanodine
      significantly increased the frequency of the cytosolic free [Ca2+] oscillations
      evoked by an alpha1 adrenergic receptor agonist. Experiments in permeabilized
      hepatocytes showed that both ryanodine and cyclic ADP-ribose evoked a slow Ca2+
      leak from intracellular stores and were able to increase the Ca2+-released
      response to a subthreshold dose of inositol 1,4,5-trisphosphate. Our findings
      suggest the presence of a novel truncated form of the type 1 ryanodine receptor
      in rat hepatocytes. Ryanodine modulates the pattern of cytosolic free [Ca2+]
      oscillations by increasing oscillation frequency. We propose that the Ca2+
      released from ryanodine receptors on the endoplasmic reticulum provides an
      increased pool of Ca2+ for positive feedback on inositol 1,4,5-trisphosphate
      receptors.

PMID- 16973608
TI  - Identification of the missing component in the mitochondrial benzamidoxime
      prodrug-converting system as a novel molybdenum enzyme.
AB  - Amidoximes can be used as prodrugs for amidines and related functional groups to
      enhance their intestinal absorption. These prodrugs are reduced to their active
      amidines. Other N-hydroxylated structures are mutagenic or responsible for toxic
      effects of drugs and are detoxified by reduction. In this study, a N-reductive
      enzyme system of pig liver mitochondria using benzamidoxime as a model substrate
      was identified. A protein fraction free from cytochrome b5 and cytochrome b5
      reductase was purified, enhancing 250-fold the minor benzamidoxime-reductase
      activity catalyzed by the membrane-bound cytochrome b5/NADH cytochrome b5
      reductase system. This fraction contained a 35-kDa protein with homologies to the
      C-terminal domain of the human molybdenum cofactor sulfurase. Here it was
      demonstrated that this 35-kDa protein contains molybdenum cofactor and forms the
      hitherto ill defined third component of the N-reductive complex in the outer
      mitochondrial membrane. Thus, the 35-kDa protein represents a novel group of
      molybdenum proteins in eukaryotes as it forms the catalytic part of a three
      component enzyme complex consisting of separate proteins. Supporting these
      findings, recombinant C-terminal domain of the human molybdenum cofactor
      sulfurase exhibited N-reductive activity in vitro, which was strictly dependent
      on molybdenum cofactor.

PMID- 16973609
TI  - The Wnt signaling receptor Lrp5 is required for mammary ductal stem cell activity
      and Wnt1-induced tumorigenesis.
AB  - Canonical Wnt signaling has emerged as a critical regulatory pathway for stem
      cells. The association between ectopic activation of Wnt signaling and many
      different types of human cancer suggests that Wnt ligands can initiate tumor
      formation through altered regulation of stem cell populations. Here we have shown
      that mice deficient for the Wnt co-receptor Lrp5 are resistant to Wnt1-induced
      mammary tumors, which have been shown to be derived from the mammary
      stem/progenitor cell population. These mice exhibit a profound delay in
      tumorigenesis that is associated with reduced Wnt1-induced accumulation of
      mammary progenitor cells. In addition to the tumor resistance phenotype, loss of
      Lrp5 delays normal mammary development. The ductal trees of 5-week-old Lrp5-/-
      females have fewer terminal end buds, which are structures critical for juvenile
      ductal extension presumed to be rich in stem/progenitor cells. Consequently, the
      mature ductal tree is hypomorphic and does not completely fill the fat pad.
      Furthermore, Lrp5-/- ductal cells from mature females exhibit little to no stem
      cell activity in limiting dilution transplants. Finally, we have shown that Lrp5
      /- embryos exhibit substantially impaired canonical Wnt signaling in the
      primitive stem cell compartment of the mammary placodes. These findings suggest
      that Lrp5-mediated canonical signaling is required for mammary ductal stem cell
      activity and for tumor development in response to oncogenic Wnt effectors.

PMID- 16973610
TI  - Cysteine-scanning mutagenesis and disulfide mapping studies of the conserved
      domain of the twin-arginine translocase TatB component.
AB  - The cytoplasmic membrane protein TatB is an essential component of the
      Escherichia coli twin-arginine (Tat) protein translocation pathway. Together with
      the TatC component it forms a complex that functions as a membrane receptor for
      substrate proteins. Structural predictions suggest that TatB is anchored to the
      membrane via an N-terminal transmembrane alpha-helix that precedes an amphipathic
      alpha-helical section of the protein. From truncation analysis it is known that
      both these regions of the protein are essential for function. Here we construct
      31 unique cysteine substitutions in the first 42 residues of TatB. Each of the
      substitutions results in a TatB protein that is competent to support Tat
      dependent protein translocation. Oxidant-induced disulfide cross-linking shows
      that both the N-terminal and amphipathic helices form contacts with at least one
      other TatB protomer. For the transmembrane helix these contacts are localized to
      one face of the helix. Molecular modeling and molecular dynamics simulations
      provide insight into the possible structural basis of the transmembrane helix
      interactions. Using variants with double cysteine substitutions in the
      transmembrane helix, we were able to detect cross-links between up to five TatB
      molecules. Protein purification showed that species containing at least four
      cross-linked TatB molecules are found in correctly assembled TatBC complexes. Our
      results suggest that the transmembrane helices of TatB protomers are in the
      center rather than the periphery of the TatBC complex.

PMID- 16973611
TI  - Crystal structure of monomeric native antithrombin reveals a novel reactive
      center loop conformation.
AB  - The poor inhibitory activity of circulating antithrombin (AT) is critical to the
      formation of blood clots at sites of vascular damage. AT becomes an efficient
      inhibitor of the coagulation proteases only after binding to a specific heparin
      pentasaccharide, which alters the conformation of the reactive center loop (RCL).
      The molecular basis of this activation event lies at the heart of the regulation
      of hemostasis and accounts for the anticoagulant properties of the low molecular
      weight heparins. Although several structures of AT have been solved, the
      conformation of the RCL in native AT remains unknown because of the obligate
      crystal contact between the RCL of native AT and its latent counterpart. Here we
      report the crystallographic structure of a variant of AT in its monomeric native
      state. The RCL shifted approximately 20 A, and a salt bridge was observed between
      the P1 residue (Arg-393) and Glu-237. This contact explains the effect of
      mutations at the P1 position on the affinity of AT for heparin and also the
      properties of AT-Truro (E237K). The relevance of the observed conformation was
      verified through mutagenesis studies and by solving structures of the same
      variant in different crystal forms. We conclude that the poor inhibitory activity
      of the circulating form of AT is partially conferred by intramolecular contacts
      that restrain the RCL, orient the P1 residue away from attacking proteases, and
      additionally block the exosite utilized in protease recognition.

PMID- 16973612
TI  - Structure of the Escherichia coli DNA polymerase III epsilon-HOT proofreading
      complex.
AB  - The epsilon subunit of Escherichia coli DNA polymerase III possesses 3'
      exonucleolytic proofreading activity. Within the Pol III core, epsilon is tightly
      bound between the alpha subunit (DNA polymerase) and subunit. Here, we present
      the crystal structure of epsilon in complex with HOT, the bacteriophage P1
      encoded homolog of , at 2.1 A resolution. The epsilon-HOT interface is defined by
      two areas of contact: an interaction of the previously unstructured N terminus of
      HOT with an edge of the epsilon central beta-sheet as well as interactions
      between HOT and the catalytically important helix alpha1-loop-helix alpha2 motif
      of epsilon. This structure provides insight into how HOT and, by implication, may
      stabilize the epsilon subunit, thus promoting efficient proofreading during
      chromosomal replication.

PMID- 16973613
TI  - Characterization of the atypical MAPK ERK4 and its activation of the MAPK
      activated protein kinase MK5.
AB  - The extracellular-regulated kinase (ERK) 4 (MAPK4) and ERK3 (MAPK6) are
      structurally related atypical MAPKs displaying major differences only in the C
      terminal extension. ERK3 is known as an unstable mostly cytoplasmic protein that
      binds, translocates, and activates the MAPK-activated protein kinase (MK) 5. Here
      we have investigated the stability and expression of ERK4 and have analyzed its
      ability to bind, translocate, and activate MK5. We show that, in contrast to
      ERK3, ERK4 is a stable protein that binds to endogenous MK5. Interaction of ERK4
      with MK5 leads to translocation of MK5 to the cytoplasm and to its activation by
      phosphorylation. In transfected HEK293 cells, where overexpressed catalytically
      dead ERK3 is able to activate MK5, catalytic activity of ERK4 is necessary for
      activation of MK5, indicating that ERK4 directly phosphorylates MK5.
      Interestingly, ERK4 dimerizes and/or oligomerizes with ERK3, suggesting that
      overexpressed inactive ERK3 recruits active endogenous ERK4 to MK5 for its
      activation. Hence, ERK3 and ERK4 cooperate in activation of MK5.

PMID- 16973614
TI  - Heterogeneous nucleotide occupancy stimulates functionality of phage shock
      protein F, an AAA+ transcriptional activator.
AB  - The catalytic AAA+ domain (PspF1-275) of an enhancer-binding protein is necessary
      and sufficient to contact sigma54-RNA polymerase holoenzyme (Esigma54), remodel
      it, and in so doing catalyze open promoter complex formation. Whether ATP binding
      and hydrolysis is coordinated between subunits of PspF and the precise nature of
      the nucleotide(s) bound to the oligomeric forms responsible for substrate
      remodeling are unknown. We demonstrate that ADP stimulates the intrinsic ATPase
      activity of PspF1-275 and propose that this heterogeneous nucleotide occupancy in
      a PspF1-275 hexamer is functionally important for specific activity. Binding of
      ADP and ATP triggers the formation of functional PspF1-275 hexamers as shown by a
      gain of specific activity. Furthermore, ATP concentrations congruent with
      stoichiometric ATP binding to PspF1-275 inhibit ATP hydrolysis and Esigma54
      promoter open complex formation. Demonstration of a heterogeneous nucleotide
      bound state of a functional PspF1-275.Esigma54 complex provides clear biochemical
      evidence for heterogeneous nucleotide occupancy in this AAA+ protein. Based on
      our data, we propose a stochastic nucleotide binding and a coordinated hydrolysis
      mechanism in PspF1-275 hexamers.

PMID- 16973616
TI  - Sulfated signal from ASJ sensory neurons modulates stomatin-dependent
      coordination in Caenorhabditis elegans.
AB  - The neuronal stomatin-like proteins UNC-1 and UNC-24 play important roles in the
      nervous system of Caenorhabditis elegans. These neuronal stomatin-like proteins
      are putative chaperone proteins that can modify volatile anesthetic sensitivity
      and disrupt coordinated locomotion. A suppressor of unc-1 and unc-24, named ssu
      1(fc73) (for suppressor of stomatin uncoordination), suppresses three phenotypes
      of neuronal stomatin-like protein deficiency as follows: volatile anesthetic
      sensitivity, uncoordinated locomotion, and a constitutive alternative
      developmental phenotype known as dauer. Here we provide the first phenotypic
      characterization of ssu-1, predicted to be the only C. elegans cytosolic alcohol
      sulfotransferase, a family of enzymes that catalyze a sulfate linkage with the
      alcohol group of small molecules for the purposes of detoxification or
      modification of signaling. In vitro enzyme analysis of bacterially expressed SSU
      1 demonstrates sulfotransferase activity and thus confirms the function predicted
      by protein sequence similarities. Whereas unc-1 is expressed in the majority of
      neurons of C. elegans, expression of SSU-1 protein in only the two ASJ amphid
      interneurons is sufficient to restore the wild type phenotype. This work
      demonstrates that SSU-1 is a functional sulfotransferase that likely modifies
      endocrine signaling in C. elegans. The expression of SSU-1 in the ASJ neurons
      refines the understanding of the function of these cells and supports their
      classification as endocrine tissue. The relationship of unc-1, unc-24, and ssu-1
      is the first association of neuronal stomatin-like proteins sharing regulatory
      roles with a sulfotransferase enzyme.

PMID- 16973615
TI  - Novel splice variants of ING4 and their possible roles in the regulation of cell
      growth and motility.
AB  - The ING4 gene is a candidate tumor suppressor gene that functions in cell
      proliferation, contact inhibition, and angiogenesis. We identified three novel
      splice variants of ING4 with differing activities in controlling cell
      proliferation, cell spreading, and cell migration. ING4_v1 (the longest splice
      variant), originally identified as ING4, encodes an intact nuclear localization
      signal (NLS), whereas the other three splice variants (ING4_v2, ING4_v3, and
      ING4_v4) lack the full NLS, resulting in increased cytoplasmic localization of
      these proteins. We found that one of the three ING4 variants, ING4_v2, is
      expressed at the same level as the original ING4 (ING4_v1), suggesting that ING4
      variants may have significant biological functions. Growth suppressive effects of
      the variants that have a partial NLS (ING4_v2 and ING4_v4) were attenuated by a
      weaker effect of the variants on p21(WAF1) promoter activation. ING4_v4 lost cell
      spreading and migration suppressive effects; on the other hand, ING4_v2 retained
      a cell migration suppressive effect but lost a cell spreading suppressive effect.
      Therefore, ING4_v2, which localized primarily into cytoplasm, might have an
      important role in the regulation of cell migration. We also found that ING4_v4
      played dominant-negative roles in the induction of p21(WAF1) promoter activation
      and in the suppression of cell motility by ING4_v1. In addition, ING4 variants
      had different binding affinities to two cytoplasmic proteins, protein-tyrosine
      phosphatase, receptor type, f polypeptide (PTPRF), interacting protein (liprin),
      alpha1, and G3BP2a. Understanding the functions of the four splice variants may
      aid in defining their roles in human carcinogenesis.

PMID- 16973617
TI  - Flow-activated chloride channels in vascular endothelium. Shear stress
      sensitivity, desensitization dynamics, and physiological implications.
AB  - Although activation of outward rectifying Cl(-) channels is one of the fastest
      responses of endothelial cells (ECs) to shear stress, little is known about these
      channels. In this study, we used whole-cell patch clamp recordings to
      characterize the flow-activated Cl(-) current in bovine aortic ECs (BAECs).
      Application of shear stress induced rapid development of a Cl(-) current that was
      effectively blocked by the Cl(-) channel antagonist 5-nitro-2-(3
      phenopropylamino)benzoic acid (100 microM). The current initiated at a shear
      stress as low as 0.3 dyne/cm(2), attained its peak within minutes of flow onset,
      and saturated above 3.5 dynes/cm(2) approximately 2.5-3.5-fold increase over pre
      flow levels). The Cl(-) current desensitized slowly in response to sustained
      flow, and step increases in shear stress elicited increased current only if the
      shear stress levels were below the 3.5 dynes/cm(2) saturation level. Oscillatory
      flow with a physiological oscillation frequency of 1 Hz, as occurs in disturbed
      flow zones prone to atherosclerosis, failed to elicit the Cl(-) current, whereas
      lower oscillation frequencies led to partial recovery of the current.
      Nonreversing pulsatile flow, generally considered protective of atherosclerosis,
      was as effective in eliciting the current as steady flow. Measurements using
      fluids of different viscosities indicated that the Cl(-) current is responsive to
      shear stress rather than shear rate. Blocking the flow-activated Cl(-) current
      abolished flow-induced Akt phosphorylation in BAECs, whereas blocking flow
      sensitive K(+) currents had no effect, suggesting that flow-activated Cl(-)
      channels play an important role in regulating EC flow signaling.

PMID- 16973618
TI  - Distinct induction patterns and functions of two closely related interferon
      inducible human genes, ISG54 and ISG56.
AB  - Human P54 and P56 proteins are tetratricopeptide proteins that are encoded by two
      closely related genes, ISG54 and ISG56. These genes are induced strongly but
      transiently when cells are treated with interferons or double-stranded RNA or
      infected with a variety of viruses. We observed that, although double-stranded
      RNA or Sendai virus infection induced the two genes with similar kinetics, their
      induction kinetics in response to interferon-beta were quite different. The
      induction kinetics by virus infection were also different between two cell lines.
      Functionally the two proteins were similar. Like P56, P54 bound to the
      translation initiation factor eIF3 and inhibited translation. However, unlike
      P56, P54 bound to both the "e" and the "c" subunits of eIF3. Consequently, P54
      inhibited two functions of eIF3. Like P56, it inhibited the ability of eIF3 to
      stabilize the eIF2 x GTP x Met-tRNA(i) ternary complex. But in addition, it also
      inhibited the formation of the 48 S pre-initiation complex between the 40 S
      ribosomal subunit and the 20 S complex composed of eIF3, ternary complex, eIF4F,
      and mRNA. Thus, although similar in structure, the human P54 and P56 proteins are
      induced differently and function differently.

PMID- 16973619
TI  - A new flavin radical signal in the Na(+)-pumping NADH:quinone oxidoreductase from
      Vibrio cholerae. An EPR/electron nuclear double resonance investigation of the
      role of the covalently bound flavins in subunits B and C.
AB  - The Na(+)-pumping NADH-ubiquinone oxidoreductase has six polypeptide subunits
      (NqrA-F) and a number of redox cofactors, including a noncovalently bound FAD and
      a 2Fe-2S center in subunit F, covalently bound FMNs in subunits B and C, and a
      noncovalently bound riboflavin in an undisclosed location. The FMN cofactors in
      subunits B and C are bound to threonine residues by phosphoester linkages. A
      neutral flavin-semiquinone radical is observed in the oxidized enzyme, whereas an
      anionic flavin-semiquinone has been reported in the reduced enzyme. For this
      work, we have altered the binding ligands of the FMNs in subunits B and C by
      replacing the threonine ligands with other amino acids, and we studied the
      resulting mutants by EPR and electron nuclear double resonance spectroscopy. We
      conclude that the sodium-translocating NADH:quinone oxidoreductase forms three
      spectroscopically distinct flavin radicals as follows: 1) a neutral radical in
      the oxidized enzyme, which is observed in all of the mutants and most likely
      arises from the riboflavin; 2) an anionic radical observed in the fully reduced
      enzyme, which is present in wild type, and the NqrC-T225Y mutant but not the NqrB
      T236Y mutant; 3) a second anionic radical, seen primarily under weakly reducing
      conditions, which is present in wild type, and the NqrB-T236Y mutant but not the
      NqrC-T225Y mutant. Thus, we can tentatively assign the first anionic radical to
      the FMN in subunit B and the second to the FMN in subunit C. The second anionic
      radical has not been reported previously. In electron nuclear double resonance
      spectra, it exhibits a larger line width and larger 8alpha-methyl proton
      splittings, compared with the first anionic radical.

PMID- 16973620
TI  - A novel regulatory metal binding domain is present in the C terminus of
      Arabidopsis Zn2+-ATPase HMA2.
AB  - HMA2 is a Zn2+-ATPase from Arabidopsis thaliana. It contributes to the
      maintenance of metal homeostasis in cells by driving Zn2+ efflux. Distinct from
      P1B-type ATPases, plant Zn2+-ATPases have long C-terminal sequences rich in Cys
      and His. Removal of the 244 amino acid C terminus of HMA2 leads to a 43%
      reduction in enzyme turnover without significant effect on the Zn2+ K(1/2) for
      enzyme activation. Characterization of the isolated HMA2 C terminus showed that
      this fragment binds three Zn2+ with high affinity (Kd = 16 +/- 3 nM). Circular
      dichroism spectral analysis indicated the presence of 8% alpha-helix, 45% beta
      sheet, and 48% random coil in the C-terminal peptide with noticeable structural
      changes upon metal binding (8% alpha-helix, 39% beta-sheet, and 52% random coil).
      Zn K-edge XAS of Zn-C-MBD in the presence of one equivalent of Zn2+ shows that
      the average zinc complex formed is composed of three His and one Cys residues.
      Upon the addition of two extra Zn2+ ions per C-MBD, these appear coordinated
      primarily by His residues thus, suggesting that the three Zn2+ binding domains
      might not be identical. Modification of His residues with diethyl pyrocarbonate
      completely inhibited Zn2+ binding to the C terminus, pointing out the importance
      of His residues in Zn2+ coordination. In contrast, alkylation of Cys with
      iodoacetic acid did not prevent Zn2+ binding to the HMA2 C terminus. Zn K-edge
      XAS of the Cys-alkylated protein was consistent with (N/O)4 coordination of the
      zinc site, with three of those ligands fitting for His residues. In summary,
      plant Zn2+-ATPases contain novel metal binding domains in their cytoplasmic C
      terminus. Structurally distinct from the well characterized N-terminal metal
      binding domains present in most P1B-type ATPases, they also appear to regulate
      enzyme turnover rate.

PMID- 16973621
TI  - A protease pathway for the repair of topoisomerase II-DNA covalent complexes.
AB  - Despite rapid advances in the field of DNA repair, little is known about the
      repair of protein-DNA adducts. Previous studies have demonstrated that
      topoisomerase II (TopII)-DNA adducts (TopII-DNA covalent complexes) are rapidly
      degraded by the proteasome. It has been hypothesized that proteasomal degradation
      of TopII-DNA covalent adducts exposes TopII-concealed DNA double-strand breaks
      (DSBs) for repair. To test this hypothesis, the anticancer drug, VP-16
      (etoposide), was employed to induce TopII-DNA covalent complexes in mammalian
      cells, and the involvement of proteasome in processing TopII-DNA covalent
      complexes into DSBs was investigated. Consistent with the hypothesis, VP-16
      induced DSBs as monitored by neutral comet assay, as well as DNA damage signals
      (e.g. gamma-H2AX) were significantly reduced in the presence of the proteasome
      inhibitor, MG132. Using both top2beta knock-out mouse embryonic fibroblasts and
      Top2beta small interfering RNA knockdown PC12 cells, as well as postmitotic
      neurons in which TopIIalpha was absent, we showed that VP-16-induced DNA damage
      signals were attenuated upon proteasome inhibition, suggesting the involvement of
      proteasome in the repair/processing of both TopIIalpha-DNA and TopIIbeta-DNA
      adducts. By contrast, hydrogen peroxide-induced gamma-H2AX was unaffected upon
      proteasome inhibition, suggesting a specific requirement of the proteasome
      pathway in the processing of TopII-DNA covalent complexes into DNA damage.

PMID- 16973622
TI  - Clioquinol, a Cu(II)/Zn(II) chelator, inhibits both ubiquitination and asparagine
      hydroxylation of hypoxia-inducible factor-1alpha, leading to expression of
      vascular endothelial growth factor and erythropoietin in normoxic cells.
AB  - We found that the Cu(II) and Zn(II)-specific chelator Clioquinol (10-50 microM)
      increased functional hypoxia-inducible factor 1alpha (HIF-1alpha) protein,
      leading to increased expression of its target genes, vascular endothelial growth
      factors and erythropoietin, in SH-SY5Y cells and HepG2 cells. Clioquinol
      inhibited ubiquitination of HIF-1alpha in a Cu(II)- and Zn(II)-dependent manner.
      It prevents FIH-1 from hydroxylating the asparagine residue (803) of HIF-1alpha
      in a Cu(II)- and Zn(II)-independent fashion. Therefore, it leads to the
      accumulation of HIF-1alpha that is prolyl but not asparaginyl hydroxylated.
      Consistent with this, co-immunoprecipitation assays showed that Clioquinol
      induced HIF-1alpha interacted with cAMP-responsive element-binding protein in
      normoxic cells, implying that Clioquinol stabilizes the trans-active form of HIF
      1alpha. Our results indicate that Clioquinol could be useful as an inducer of HIF
      1alpha and its target genes in ischemic diseases.

PMID- 16973623
TI  - Mutant huntingtin expression induces mitochondrial calcium handling defects in
      clonal striatal cells: functional consequences.
AB  - Huntington disease (HD) is caused by a pathological elongation of CAG repeats in
      the huntingtin protein gene and is characterized by atrophy and neuronal loss
      primarily in the striatum. Mitochondrial dysfunction and impaired Ca2+
      homeostasis in HD have been suggested previously. Here, we elucidate the effects
      of Ca2+ on mitochondria from the wild type (STHdhQ7/Q7) and mutant
      (STHdhQ111/Q111) huntingtin-expressing cells of striatal origin. When treated
      with increasing Ca2+ concentrations, mitochondria from mutant huntingtin
      expressing cells showed enhanced sensitivity to Ca2+, as they were more sensitive
      to Ca2+-induced decreases in state 3 respiration and DeltaPsim, than mitochondria
      from wild type cells. Further, mutant huntingtin-expressing cells had a reduced
      mitochondrial Ca2+ uptake capacity in comparison with wild type cells. Decreases
      in state 3 respiration were associated with increased mitochondrial membrane
      permeability. The DeltaPsim defect was attenuated in the presence of ADP and the
      decreases in Ca2+ uptake capacity were abolished in the presence of Permeability
      Transition Pore (PTP) inhibitors. These findings clearly indicate that mutant
      huntingtin-expressing cells have mitochondrial Ca2+ handling defects that result
      in respiratory deficits and that the increased sensitivity to Ca2+ induced
      mitochondrial permeabilization maybe a contributing mechanism to the
      mitochondrial dysfunction in HD.

PMID- 16973624
TI  - RGS3 and RGS4 differentially associate with G protein-coupled receptor-Kir3
      channel signaling complexes revealing two modes of RGS modulation. Precoupling
      and collision coupling.
AB  - RGS3 and RGS4 are GTPase-activating proteins expressed in the brain and heart
      that accelerate the termination of G(i/o)- and G(q)-mediated signaling. We report
      here the determinants mediating selective association of RGS4 with several G
      protein-coupled receptors (GPCRs) that form macromolecular complexes with
      neuronal G protein-gated inwardly rectifying potassium (Kir3 or GIRK) channels.
      Kir3 channels are instrumental in regulating neuronal firing in the central and
      peripheral nervous system and pacemaker activity in the heart. By using an
      epitope-tagged degradation-resistant RGS4 mutant, RGS4(C2V), immunoprecipitation
      of several hemagglutinin-tagged G(i/o)-coupled and G(q)-coupled receptors
      expressed in Chinese hamster ovary (CHO-K1) cells readily co-precipitated both
      Kir3.1/Kir3.2a channels and RGS4(C2V). In contrast to RGS4(C2V), the closely
      related and functionally active RGS3 "short" isoform (RGS3s) did not interact
      with any of the GPCR-Kir3 channel complexes examined. Deletion and chimeric RGS
      constructs indicate both the N-terminal domain and the RGS domain of RGS4(C2V)
      are necessary for association with m2 receptor-Kir3.1/Kir3.2a channel complexes,
      where the GPCR was found to be the major target for RGS4(C2V) interaction. The
      functional impact of RGS4(C2V) "precoupling" to the GPCR-Kir3 channel complex
      versus RGS3s "collision coupling" was a 100-fold greater potency in the
      acceleration of G protein-dependent Kir3 channel-gating kinetics with no
      attenuation in current amplitude. These findings demonstrate that RGS4, a highly
      regulated modulator and susceptibility gene for schizophrenia, can directly
      associate with multiple GPCR-Kir3 channel complexes and may affect a wide range
      of neurotransmitter-mediated inhibitory and excitatory events in the nervous and
      cardiovascular systems.

PMID- 16973625
TI  - Coordination of JNK1 and JNK2 is critical for GADD45alpha induction and its
      mediated cell apoptosis in arsenite responses.
AB  - Arsenite is a well documented environmental pathogen, whereas it has also been
      applied as medication to treat various neoplasmas. The pathogenic and therapeutic
      effects of arsenite are associated with cellular apoptotic responses. However,
      the molecular mechanisms of arsenite-induced apoptosis are not very well
      understood. Our previous study has shown that arsenite exposure is able to
      activate JNKs, which subsequently mediate the apoptotic outcome. The present
      study further revealed that the coordination of JNK1 and JNK2 was critical for
      the arsenite-induced expression of GADD45alpha (growth arrest and DNA damage
      45alpha), which in turn mediated the cellular apoptosis. The arsenite-induced
      apoptosis and GADD45alpha expression were significantly impaired in mouse
      embryonic fibroblasts deficient in either jnk1 (JNK1-/-) or jnk2 (JNK2-/-).
      Knockdown of GADD45alpha by its specific small interfering RNA also dramatically
      reduced the apoptotic responses, and overexpression of GADD45alpha in either JNK1
      /- or JNK2-/- mouse embryonic fibroblasts partially resensitized the cell death.
      Furthermore, it was found that the regulation of GADD45alpha by JNK1 and JNK2 was
      achieved through mediating the activation of c-Jun, since in the JNK1-/- and JNK2
      /- cells the c-Jun activation was impaired, and overexpression of the dominant
      negative mutant of c-Jun (TAM67) in wild type cells could also block GADD45alpha
      induction as well as cellular apoptosis. Our results demonstrate that the
      coordination of JNK1 and JNK2 is critical for c-Jun/GADD45alpha-mediated cellular
      apoptosis induced by arsenite.

PMID- 16973626
TI  - Human hepatitis B viral e antigen interacts with cellular interleukin-1 receptor
      accessory protein and triggers interleukin-1 response.
AB  - Human hepatitis B virus (HBV) can cause acute and chronic hepatitis, cirrhosis,
      and hepatocellular carcinoma. HBV e antigen (HBeAg), a secreted protein and not
      required for viral replication, is thought to play an immunoregulatory role
      during viral infection. However, the functional involvement of HBeAg in host
      immune response has not been fully elucidated. We report in this study that HBeAg
      can bind to interleukin-1 receptor accessory protein (IL-1RAcP). Interleukin-1
      (IL-1) plays an important role in inflammation and regulation of immune response,
      and membrane form of IL-1RAcP (mIL-1RAcP) is an essential component of trimeric
      IL-1/IL-1 receptor/mIL-1RAcP complex. We show that glutathione S-transferase- or
      polyhistidine-tagged recombinant HBeAg can interact with endogenous mIL-1RAcP in
      vitro. Purified (His)6-HBeAg added in the culture medium can interact with
      overexpressed FLAG-tagged mIL-1RAcP in vivo. Indirect immunofluorescence and
      confocal microscopy show that HBeAg colocalizes with mIL-1RAcP on the cell
      surface. Furthermore, HBeAg is able to induce the interaction of IL-1 receptor I
      (IL-1RI) with mIL-1RAcP and trigger the recruitment of adaptor protein myeloid
      differentiation factor 88 (MyD88) to the IL-1RI/mIL-1RAcP complex. Assembly and
      activation of IL-1RI/mIL-1RAcP signaling complex by HBeAg can activate downstream
      NF-kappaB pathway through IkappaB degradation, induce NF-kappaB-dependent
      luciferase expression, and induce the expression of IL-1-responsive genes.
      Silencing of IL-1RAcP by small interfering RNA dramatically abolishes HBeAg
      mediated NF-kappaB activation. These results demonstrate that HBeAg can trigger
      host IL-1 response by binding to mIL-1RAcP. The interaction of HBeAg with mIL
      1RAcP may play an important role in modulating host immune response in acute and
      chronic HBV infection.

PMID- 16973628
TI  - Solute response to changing nutrient loads in soil and walled ceramic cup
      samplers under continuous extraction.
AB  - This report evaluates a vacuum-assisted walled percolation sampler preconditioned
      in soil, and examines the dynamic response of leachate solutes. The 20-cm walled
      percolation sampler extracted soil water under continuous tension via a ceramic
      cup collector embedded in a silica flour layer, whose upper surface interfaced
      with field soil. In the laboratory, alternating solutions with high and low NO3-N
      (232 or 3.6 mg L(-1)), molybdate-reactive P (MRP) (1.75 or 0.0 mg L(-1)), K+ (568
      or 3.6 mg L(-1)), and Br- (9.6 or 0.0 mg L(-1)) concentrations were delivered
      directly to the (i) sampler ceramic cup; (ii) silica flour bed surface, or (iii)
      12-mm soil layer placed over the silica flour bed. For alternating input
      solutions delivered to the silica-flour bed surface, (i) solute breakthrough (95%
      equivalency) occurred in 4 pore volumes and was the same for both the high and
      low concentration input phases of the application, and (ii) concentrations of NO3
      N, Br-, and MRP in cumulative extracted water volumes were within 5% of those in
      corresponding input volumes. Alternating nutrient loads from high to low levels
      in the fixed flow rate input waters caused excess MRP (1.6 times that in the high
      concentration MRP solution) to leach from the calcareous soil. The dynamic
      character of P transport in K-fertilized soils deserves further study and may
      have important environmental implications.

PMID- 16973627
TI  - Structural and functional insights into the regulation of Arabidopsis AGC VIIIa
      kinases.
AB  - The AGCVIIIa kinases of Arabidopsis are members of the eukaryotic PKA, PKG, and
      PKC group of regulatory kinases. One AGCVIIIa kinase, PINOID (PID), plays a
      fundamental role in the asymmetrical localization of membrane proteins during
      polar auxin transport. The remaining 16 AGCVIIIa genes have not been associated
      with single mutant phenotypes, suggesting that the corresponding kinases function
      redundantly. Consistent with this idea, we find that the genes encoding the
      Arabidopsis AGCVIIIa kinases have spatially distinct, but overlapping, expression
      domains. Here we show that the majority of Arabidopsis AGCVIIIa kinases are
      substrates for the 3-phosphoinositide-dependent kinase 1 (PDK1) and that trans
      phosphorylation by PDK1 correlates with activation of substrate AGCVIIIa kinases.
      Mutational analysis of two conserved regulatory domains was used to demonstrate
      that sequences located outside of the C-terminal PDK1 interaction (PIF) domain
      and the activation loop are required for functional interactions between PDK1 and
      its substrates. A subset of GFP-tagged AGCVIIIa kinases expressed in
      Saccharomyces cerevisiae and tobacco BY-2 cells were preferentially localized to
      the cytoplasm (AGC1-7), nucleus (WAG1 and KIPK), and the cell periphery (PID). We
      present evidence that PID insertion domain sequences are sufficient to direct the
      observed peripheral localization. We find that PID specifically but non
      selectively binds to phosphoinositides and phosphatidic acid, suggesting that PID
      might directly interact with the plasma membrane through protein-lipid
      interactions. The initial characterization of the AGCVIIIa kinases presented here
      provides a framework for elucidating the physiological roles of these kinases in
      planta.

PMID- 16973629
TI  - Bioconversion of selenate in methanogenic anaerobic granular sludge.
AB  - The capacity of anaerobic granular sludge to remove selenate from contaminated
      wastewater was investigated. The potential of different types of granular sludge
      to remove selenate from the liquid phase was compared to that of suspended sludge
      and contaminated soil and sediment samples. The selenate removal rates ranged
      from 400 to 1500 microg g VSS(-1) h(-1), depending on the source of biomass,
      electron donor, and the initial selenate concentration. The granular structure
      protects the microorganisms when exposed to high selenate concentrations (0.1 to
      1 mM). Anaerobic granular sludge "Eerbeek," originating from a UASB reactor
      treating paper mill wastewater, removed about 90, 50, and 36% of 0.1, 0.5, and 1
      mM of Se, respectively, from the liquid phase when incubated with 20 mM lactate
      at 30 degrees C and pH 7.5. Selenite, elemental Se (Se(o)), and metal selenide
      precipitates were the conversion products. Enrichments from the anaerobic
      granular sludge "Eerbeek" were able to convert 90% of the 10-mM selenate to Se(o)
      at a rate of 1505 microg Se(VI) g cells(-1) h(-1), a specific growth rate of
      0.0125 g cells h(-1), and a yield of 0.083 g cells mg Se(-1). Both microbial
      metabolic processes (e.g dissimilatory reduction) as well as microbially mediated
      physicochemical mechanisms (adsorption and precipitation) contribute to the
      removal of selenate from the Se-containing medium.

PMID- 16973630
TI  - Contrasting pathways of assimilation: stable isotope assessment of fish exposure
      to pulp mill effluents.
AB  - Fish are commonly used for monitoring the quality of waters receiving pulp mill
      effluents (PMEs). Isotopic assays of fish tissues have the potential to provide
      empirical evidence to link an effluent source to exposure. We show in a 45-d
      factorial laboratory experiment that different exposure pathways lead to isotopic
      signatures in fish tissue. Rainbow trout (Oncorhynchus mykiss) were exposed to
      10% PME in three ways; direct exposure through addition of PME to aquaria,
      indirect exposure through invertebrate food consumption (Chironomus tentans
      cultured in 10% PME), and a combination of both exposure pathways. Of the four
      stable isotopes measured (delta13C, delta15N, delta34S, delta37Cl), delta13C,
      delta34S, and delta37Cl showed significant differences in exposed animal tissues.
      Delta37Cl of fish muscle tissue showed consistent differences across trophic
      levels and revealed contrasting pathways of PME exposure. Contrasting delta 37Cl
      values in C. tentans due to the presence or absence of 10% PME did not translate
      into delta37Cl differences in fish. Rather, delta37Cl ratios of fish muscle
      tissue were specifically related to 10% PME exposure in the aquaria (waterborne
      exposure pathway). Feasible distributions of 37Cl source contributions for
      observed mixture ratios confirmed that PME accounted for observed differences in
      delta37Cl among treatments. Direct uptake of chloride ions across gill surfaces
      is the most likely pathway for assimilation of PME into fish tissues. Considering
      the variability of PMEs and receiving environments, use of a multi-isotope
      approach is recommended for tracing exposure of fish. Use of 37Cl should also be
      considered in light of its alternative assimilation pathway.

PMID- 16973631
TI  - Combined effects of constant versus variable intensity simulated rainfall and
      reduced tillage management on cotton preemergence herbicide runoff.
AB  - Pesticide runoff research relies heavily on rainfall simulation experiments. Most
      are conducted at a constant intensity, i.e., at a fixed rainfall rate; however,
      large differences in natural rainfall intensity is common. To assess implications
      we quantified runoff of two herbicides, fluometuron and pendimethalin, and
      applied preemergence after planting cotton on Tifton loamy sand. Rainfall at
      constant and variable intensity patterns representative of late spring
      thunderstorms in the Atlantic Coastal Plain region of Georgia (USA) were
      simulated on 6-m2 plots under strip- (ST) and conventional-tillage (CT)
      management. The variable pattern produced significantly higher runoff rates of
      both compounds from CT but not ST plots. However, on an event-basis, runoff
      totals (% applied) were not significantly different, with one exception:
      fluometuron runoff from CT plots. There was about 25% more fluometuron runoff
      with the variable versus the constant intensity pattern (P = 0.10). Study results
      suggest that conduct of simulations using variable intensity storm patterns may
      provide more representative rainfall simulation-based estimates of pesticide
      runoff and that the greatest impacts will be observed with CT. The study also
      found significantly more fluometuron in runoff from ST than CT plots. Further
      work is needed to determine whether this behavior may be generalized to other
      active ingredients with similar properties [low K(oc) (organic carbon partition
      coefficient) approximately 100 mL g(-1); high water solubility approximately 100
      mg L(-1)]. If so, it should be considered when making tillage-specific herbicide
      recommendations to reduce runoff potential.

PMID- 16973632
TI  - Theoretical comparison of how soil processes affect uptake of metals by diffusive
      gradients in thinfilms and plants.
AB  - The theoretical basis for using measurements of metal uptake by the technique of
      diffusive gradients in thinfilms (DGT) to mimic processes in soils that affect
      uptake of metals by plants is examined. The uptake of metals by plants and DGT
      were compared conceptually and quantitatively by using the classic Barber model
      of plant uptake and the DIFS (DGT-induced fluxes in soils) model of uptake by
      DGT. For most metals and plants considered, uptake fluxes were similar to those
      induced by DGT using the most common gel layer thicknesses of 0.2 to 2 mm.
      Consequently DGT perturbs the chemical equilibrium of metals in the soil solution
      and between soil solution and solid phase, to a similar extent to plants, and
      therefore induces a similar balance in supply by diffusion and by release from
      the solid phase. DIFS was used to show that desorption kinetics, which are not
      considered by the plant uptake model, are likely important for uptake when the
      capacity of the soil solid phase is large. Model calculations showed that mass
      flow into a plant root would only contribute appreciably to the total flux of
      metal under circumstances when the solid phase reservoir of metal was very low.
      Generally, however, DGT is likely to emulate supply processes from the soil that
      govern uptake of metal by plants. Exceptions are likely to be found in poorly
      buffered soils (typically sandy and/or low pH), and at very high concentrations
      of metals in soil solution, such that the soil solution concentration at the
      plant root interface is higher than the Michaelis-Menten constant (Km).

PMID- 16973633
TI  - Evaluation of the ADAPT model for simulating nitrogen dynamics in a tile-drained
      agricultural watershed in central Illinois.
AB  - Assessing the accuracy of agronomic and water quality simulation models in
      different soils, land-use systems, and environments provides a basis for using
      and improving these models. We evaluated the performance of the ADAPT model for
      simulating riverine nitrate-nitrogen (NO3-N) export from a 1500-km2 watershed in
      central Illinois, where approximately 85% of the land is used for maize-soybean
      production and tile drainage is common. Soil chemical properties, crop nitrogen
      (N) uptake coefficient, dry matter ratio, and a denitrification reduction
      coefficient were used as calibration parameters to optimize the fit between
      measured and simulated NO3-N load from the watershed for the 1989 to 1993 period.
      The applicability of the calibrated parameter values was tested by using these
      values for simulating the 1994 to 1997 period on the same watershed. Willmott's
      index of agreement ranged from 0.91 to 0.97 for daily, weekly, monthly, and
      annual comparisons of riverine nitrate N loads. Simulation accuracy generally
      decreased as the time interval decreased. Willmott's index for simulated crop
      yields ranged from 0.91 to 0.99; however, observed crop yields were used as input
      to the model. The partial N budget results suggested that 52 to 72 kg N ha(-1)
      yr(-1) accumulated in the soil, but simulated biological N fixation associated
      with soybeans was considerably greater than literature values for the region.
      Improvement of the N fixation algorithms and incorporation of mechanisms that
      describe soybean yield in response to environmental conditions appear to be
      needed to improve the performance of the model.

PMID- 16973634
TI  - Stream buffer effectiveness in an agriculturally influenced area, southwestern
      Georgia: responses of water quality, macroinvertebrates, and amphibians.
AB  - To determine useful metrics for assessing stream water quality in the
      Southeastern Coastal Plain, we examined differences among two buffered and three
      unbuffered streams in an agricultural landscape in southwestern Georgia.
      Potential indicators included amphibian diversity and abundance, aquatic
      macroinvertebrate populations, riparian vegetative structure, water quality, and
      stream physical parameters. Variability among sites and treatments (buffered vs.
      unbuffered) existed, with sites in the same treatment as most similar, and
      disturbances from a nearby eroding gully strongly affecting one unbuffered site.
      Of the invertebrate metrics examined, percentages of clingers, Ephemeroptera
      Plecoptera-Trichoptera (EPT), Elmidae (Coleoptera), Crustacea (Decapoda and
      Amphipoda), and dipterans were found to be possible indicators of stream health
      for perennial streams within this region. Overall, buffered sites showed higher
      percentages of sensitive invertebrate groups and showed lower and more stable
      concentrations of nitrate N, suspended solids, and fecal coliforms (FCs). Percent
      canopy cover was similar among sites; however, riparian vegetative coverage and
      percent leaf litter were greatest at buffered sites. No differences in amphibian
      abundance, presence, and absence within the riparian area were apparent between
      sites; however, instream larval salamanders were more abundant at buffered
      streams. In this study, stream buffers appeared to decrease nutrient and sediment
      loads to adjacent streams, enhancing overall water quality. Selected benthic
      macroinvertebrate metrics and amphibian abundance also appeared sensitive to
      agricultural influences. Amphibians show potential as indicator candidates,
      however further information is needed on their responses and tolerances to
      disturbances from the microhabitat to landscape levels.

PMID- 16973635
TI  - Response of spinach and komatsuna to biogas effluent made from source-separated
      kitchen garbage.
AB  - Recycling of kitchen garbage is an urgent task for reducing public spending and
      environmental burdens by incineration and/or landfill. There is an interesting
      regional effort in Ogawa, Saitama prefecture, Japan, in which source-separated
      kitchen garbage is anaerobically fermented with a biogas plant and the resultant
      effluent is used as a quick-release organic fertilizer by surrounding farmers.
      However, scientific assessments of fertilizer values and risks in the use of the
      effluent were lacking. Thus, a field experiment was conducted from 2003 to 2004
      in Tohoku National Agricultural Research Center to grow spinach (Spinacia
      oleracea L.) and komatsuna (Brassica rapa var. perviridis L. H. Bailey) for
      evaluating the fertilizer value of the kitchen garbage effluent (KGE), nitrate,
      coliform group (CG), Escherichia coli, fecal streptococci (FS), and Vibrio
      parahaemolyticus concentrations of KGE and in the soil and the plant leaves. A
      cattle manure effluent (CME) and chemical fertilizers (NPK) were used as
      controls. Total nitrogen (N) and ammonium N concentrations of the KGE were 1.47
      and 1.46 g kg(-1), respectively. The bacteria tested were detected in both biogas
      effluents in the order of 2 to 3 log CFU g(-1), but there was little evidence
      that the biogas effluents increased these bacteria in the soil and the plant
      leaves. At the rate of 22 g N m(-2), yield, total N uptake, apparent N recovery
      rate, and leaf nitrate ion concentration at harvest of spinach and komatsuna in
      the KGE plot were mostly comparable to those in the NPK and CME plots. We
      conclude that the KGE is a quick-release N fertilizer comparable to chemical
      fertilizers and does not cause contamination of CG, E. coli, FS, or V.
      parahaemolyticus in the soil and spinach and komatsuna leaves.

PMID- 16973636
TI  - Metal distribution and stability in constructed wetland sediment.
AB  - The A-01 wetland treatment system (WTS) is a surface flow wetland planted with
      giant bulrush [Schoenoplectus californicus (C.A. Mey.) Palla] that is designed to
      remove Cu and other metals from the A-01 National Pollution Discharge Elimination
      System (NPDES) effluent at the Savannah River Site near Aiken, SC. Copper, Zn,
      and Pb concentrations in water were usually reduced 60 to 80% by passage through
      the treatment system. The Cu concentrations in the wetland sediments increased
      from about 4 to 205 and 796 mg kg(-1), respectively, in the organic and floc
      sediment layers in cell 4A over a 5-yr period. Metal concentrations were higher
      in the two top layers of sediment (i.e., the floc and organic layers) than in the
      deeper inorganic layers. Sequential extraction was used to evaluate
      remobilization and retention of Cu, Pb, Zn, Mn, and Fe in the wetland sediment.
      Metal remobilization was determined by the potentially mobile fraction (PMF) and
      metal retention by the recalcitrant factor (RF). The PMF values were high in the
      floc layer but comparatively low in the organic and inorganic layers. High RF
      values for Cu, Zn, and Pb in the organic and inorganic layers indicated that
      these metals were strongly bound in the sediment. The RF values for Mn were lower
      than for the other elements especially in the floc layer, indicating low
      retention or binding capacity. Retention of contaminants was also evaluated by
      distribution coefficient (Kd) values. Distribution coefficient (Kd) values were
      lower for Cu and Zn than for Pb, indicating a smaller exchangeable fraction for
      Pb.

PMID- 16973637
TI  - Sorption of atmospheric ammonia by soil and perennial grass downwind from two
      large cattle feedlots.
AB  - Livestock manure in feedlots releases ammonia (NH3), which can be sorbed by
      nearby soil and plants. Ammonia sorption by soil and its effects on soil and
      perennial grass N contents downwind from two large cattle feedlots in Alberta,
      Canada were investigated from June to October 2002. Atmospheric NH3 sorption was
      measured weekly by exposing air-dried soil at sampling points downwind along 1700
      m transects. The amount of NH3 sorbed by soil was 2.60 to 3.16 kg N ha(-1) wk(-1)
      near the source, declining to about 0.25 kg N ha(-1) wk(-1) 1700 m downwind,
      reflecting diminishing atmospheric NH3 concentrations. Ammonia sorption at a
      control site away from NH3 sources was much lower: 0.085 kg N ha(-1) wk(-1).
      Based on these rates, about 19% of emitted NH3 is sorbed by soil within 1700 m
      downwind of feedlots. Field soil and grass samples from the transect lines were
      analyzed for total N (TN) and KCl-extractable N content (soil only). Nitrate N
      content in field soil followed a trend similar to that of atmospheric NH3
      sorption. Soil TN contents, because of high background levels, showed no clear
      pattern. The TN content of grass, downwind of the newer feedlot, followed a
      pattern similar to that of NH3 sorption; downwind of the older feedlot, grass TN
      was correlated to soil TN. Our results suggest that atmospheric NH3 from
      livestock operations can contribute N to local soil and vegetation, and may need
      to be considered when determining fertilizer rates and assessing environmental
      impact.

PMID- 16973638
TI  - Prognostic value of symptoms during a normal or nonspecific electrocardiogram in
      emergency department patients with potential acute coronary syndrome.
AB  - OBJECTIVES: Emergency department (ED) patients with symptoms concerning for acute
      coronary syndrome (ACS) and a normal electrocardiogram (ECG) are at risk for
      adverse cardiovascular events. The authors hypothesized that patients with a
      normal or nonspecific ECG during symptoms have a lower risk for ACS than do those
      who are asymptomatic. METHODS: This was a prospective cohort study of ED patients
      with potential ACS. Outcomes were acute myocardial infarction (AMI), ACS, and 30
      day cardiovascular events (death, AMI, revascularization). Fisher's exact test, t
      tests, and logistic regression were used for data analysis. RESULTS: Of 2,593
      patient visits, 2,007 patients had normal or nonspecific ECG findings. There were
      1,196 who had symptoms during ECG, whereas 811 did not. Patients with symptoms at
      ECG acquisition were younger (49.9 vs. 55.2 years; p < 0.001) and were more
      likely to be black (70% vs. 64%; p = 0.002), female (63% vs. 58%; p = 0.03), and
      to have used cocaine (5% vs. 2%; p = 0.004). They were less likely to have
      hypertension (49% vs. 58%; p < 0.001), and diabetes (22% vs. 17%; p = 0.002).
      Patients with and without symptoms were equally likely to have AMI (both 2.8%; p
      > 0.99), ACS (10.1% vs. 11.5%; p = 0.34), and 30-day adverse outcomes (both 5.3%;
      p > 0.99). After adjustment for baseline cardiovascular-risk factors, odds ratios
      for patients with symptoms at the time of ECG acquisition were not significantly
      different for any of the outcomes: AMI (1.1; 95% confidence interval [CI] = 0.6
      to 1.9); ACS (1.1; 95% CI = 0.8 to 1.4); or 30-day events (1.2; 95% CI = 0.8 to
      1.9). CONCLUSIONS: Patients who are symptomatic during acquisition of a normal or
      nonspecific ECG have rates of adverse cardiovascular events similar to those of
      patients without symptoms. Clinicians should not rely on the absence of ECG
      abnormalities during symptoms to help exclude ACS.

PMID- 16973639
TI  - R-wave amplitude in lead II of an electrocardiograph correlates with central
      hypovolemia in human beings.
AB  - OBJECTIVES: Previous animal and human experiments have suggested that reduction
      in central blood volume either increases or decreases the amplitude of R waves in
      various electrocardiograph (ECG) leads depending on underlying pathophysiology.
      In this investigation, we used graded central hypovolemia in adult volunteer
      subjects to test the hypothesis that moderate reductions in central blood volume
      increases R-wave amplitude in lead II of an ECG. METHODS: A four-lead ECG
      tracing, heart rate (HR), estimated stroke volume (SV), systolic blood pressure,
      diastolic blood pressure, and mean arterial pressure were measured during
      baseline supine rest and during progressive reductions of central blood volume to
      an estimated volume loss of >1,000 mL with application of lower-body negative
      pressure (LBNP) in 13 healthy human volunteer subjects. RESULTS: Lower-body
      negative pressure resulted in a significant progressive reduction in central
      blood volume, as indicated by a maximal decrease of 65% in SV and maximal
      elevation of 56% in HR from baseline to -60 mm Hg LBNP. R-wave amplitude
      increased (p < 0.0001) linearly with progressive LBNP. The amalgamated
      correlation (R2) between average stroke volume and average R-wave amplitude at
      each LBNP stage was -0.989. CONCLUSIONS: These results support our hypothesis
      that reduction of central blood volume in human beings is associated with
      increased R-wave amplitude in lead II of an ECG.

PMID- 16973640
TI  - Digital versus local anesthesia for finger lacerations: a randomized controlled
      trial.
AB  - OBJECTIVES: To compare the pain of needle insertion, anesthesia, and suturing in
      finger lacerations after local anesthesia with prior topical anesthesia with that
      experienced after digital anesthesia. METHODS: This was a randomized controlled
      trial in a university-based emergency department (ED), with an annual census of
      75,000 patient visits. ED patients aged > or = 8 years with finger lacerations
      were enrolled. After standard wound preparation and 15-minute topical application
      of lidocaine-epinephrine-tetracaine (LET) in all wounds, lacerations were
      randomized to anesthesia with either local or digital infiltration of 1%
      lidocaine. Pain of needle insertion, anesthetic infiltration, and suturing were
      recorded on a validated 100-mm visual analog scale (VAS) from 0 (none) to 100
      (worst); also recorded were percentage of wounds requiring rescue anesthesia;
      time until anesthesia; percentage of wounds with infection or numbness at day 7.
      Outcomes were compared by using Mann-Whitney U and chi-square tests. A sample of
      52 patients had 80% power to detect a 15-mm difference in pain scores. RESULTS:
      Fifty-five patients were randomized to digital (n = 28) or local (n = 27)
      anesthesia. Mean age (+/-SD) was 38.1 (+/-16.8) years, 29% were female. Mean (+/
      SD) laceration length and width were 1.7 (+/-0.7) cm and 2.0 (+/-1.0) mm,
      respectively. Groups were similar in baseline patient and wound characteristics.
      There were no between-group differences in pain of needle insertion (mean
      difference, 1.3 mm; 95% confidence interval [CI] = -17.0 to 14.3 mm); anesthetic
      infiltration (mean difference, 2.3 mm; 95% CI = -19.7 to 4.4 mm), or suturing
      (mean difference, 7.6 mm; 95% CI = -3.3 to 21.1 mm). Only one patient in the
      digital anesthesia group required rescue anesthesia. There were no wound
      infections or persistent numbness in either group. CONCLUSIONS: Digital and local
      anesthesia of finger lacerations with prior application of LET to all wounds
      results in similar pain of needle insertion, anesthetic infiltration, and pain of
      suturing.

PMID- 16973641
TI  - Length of stay by route of contrast administration for diagnosis of appendicitis
      by computed-tomography scan.
AB  - OBJECTIVES: Studies show equivalent accuracy of abdominal computed tomography
      (CT) using rectal contrast compared with oral contrast for diagnosing
      appendicitis. The authors evaluated whether emergency department (ED) length of
      stay and satisfaction differed by route of contrast administration for abdominal
      CT. METHODS: This before-and-after intervention evaluated adult patients in an
      urban academic ED who were undergoing abdominal CT to screen for suspected
      appendicitis. Phase 1 subjects had a CT after oral contrast. Phase 2 patients had
      a CT after rectal contrast infused by gravity drip. Patients were interviewed
      after CT scan to assess satisfaction and discomfort. The primary outcome was ED
      length of stay. Medians, 95% binomial confidence intervals (CI), and Wilcoxon
      rank sum test of differences were calculated. RESULTS: One hundred twelve
      patients were enrolled; half received rectal contrast. There was a significant
      decrease in length of stay for patients who were administered rectal contrast
      (261 min, 95% CI = 236 to 305 min) vs. oral contrast (332 min, 95% CI = 299 to
      362 min), p = 0.009. Although subjects in the rectal-contrast group waited 65
      minutes longer than did oral-contrast patients before receiving contrast after
      the CT order, the time from contrast administration to CT was 13 minutes, vs. 150
      minutes for patients receiving oral contrast (p < 0.001). Patient satisfaction
      and discomfort did not differ by route of contrast administration. CONCLUSIONS:
      Rectal contrast for patients undergoing abdominal CT to rule out appendicitis
      reduced ED length of stay by more than an hour and did not affect patient
      satisfaction or discomfort. Rectal-contrast administration for abdominal CT may
      significantly shorten patient throughput time for individuals undergoing
      evaluation for appendicitis.

PMID- 16973642
TI  - Obesity and the risk for mental disorders in a representative German adult
      sample.
AB  - BACKGROUND: A systematic approach to examining associations among obesity and
      socio-demographic determinants, psychological problems, and mental disorders in
      epidemiological samples is missing. METHODS: Within the representative German
      Health Interview and Examination Survey and its Mental Health Supplement (GHS
      MHS), 4181 subjects (age 18-65 years) took part in a physical examination
      (including measurement of body weight and height) and a standardized
      psychological interview (M-CIDI). Obesity (BMI > 30 kg/m(2)), somatic diseases,
      socio-economic variables, health-related quality of life (SF-36), and mental
      disorders (DSM-IV) were assessed. Data were analysed by logistic regression
      analyses. RESULTS: Prevalence of obesity was 18.5%. There was a strong
      association between obesity and somatic conditions, as well as to low socio
      economic status (SES). No psychosocial disadvantages (e.g. regarding social
      relationships, impairment due to mental health problems, depressed feelings) for
      the obese individuals were found. With the exception of a higher prevalence of
      anxiety disorders in obese men (12.5 versus 8.5%, OR = 1.53, CI = 1.06-2.21,
      disappearing when controlled for number of somatic conditions), obese persons
      showed no elevated rates of mental disorders. DISCUSSION: Obesity is associated
      with a low SES and some somatic disadvantages but not with other social or
      emotional disadvantages that have been often assumed to be very prevalent in that
      group. From the population-based perspective, obesity per se seems not to be
      associated with a higher risk for suffering from mental disorders, whereas
      relations between specific aspects of obesity and specific types of
      psychopathology still need further study.

PMID- 16973643
TI  - A critical comment on heat wave response plans.

PMID- 16973644
TI  - Effects of isoflurane and enflurane on GABAA and glycine receptors contribute
      equally to depressant actions on spinal ventral horn neurones in rats.
AB  - BACKGROUND: Volatile anaesthetics are widely used agents in clinical anaesthesia,
      although their mechanism of action is poorly understood. In particular, the
      dominant molecular mechanisms by which volatile anaesthetics depress spinal
      neurones and thereby mediate spinal effects such as immobility have recently
      become a matter of dispute. As GABAA and glycine receptors are potential
      candidates we investigated the impact of both receptor systems in mediating the
      depressant effects of isoflurane and enflurane on spinal neurones in rats.
      METHODS: The effects of isoflurane and enflurane on spontaneous action potential
      firing were investigated by extracellular voltage recordings from ventral horn
      interneurones in cultured spinal cord tissue slices obtained from embryonic rats
      (E 14-15). RESULTS: Isoflurane and enflurane reduced spontaneous action potential
      firing. Concentrations causing half-maximal effects (isoflurane: 0.17 mM;
      enflurane: 0.50 mM) were less than EC50-immobility (isoflurane: 0.32 mM;
      enflurane: 0.62 mM). Effects of isoflurane were mediated by 39% by glycine
      receptors and 36% by GABAA receptors. The effects of enflurane were mediated 26%
      by GABAA receptors and 29% by glycine receptors. CONCLUSION: These results
      demonstrate that the effects of isoflurane and enflurane on GABAA and glycine
      receptors contribute almost equally to their depressant actions on spinal ventral
      horn neurones in rats. The fraction of inhibition mediated by both receptor
      systems differs between specific volatile anaesthetics. Our data argue against
      the theory that a dominant molecular mechanism accounts for spinal effects of
      volatile anaesthetics.

PMID- 16973645
TI  - A novel acoustic window for trans-oesophageal echocardiography by using a saline
      filled endotracheal balloon.
AB  - BACKGROUND: The main structures anterior to the trachea are frequently poorly
      visualized by trans-oesophageal echocardiography (TEE) because of the tracheal
      air column. We studied a new acoustic window for TEE imaging of large vessels
      anterior to the trachea by using a saline-filled endotracheal balloon. METHODS:
      Cardiac surgery patients were studied. After ventilation was discontinued at the
      beginning of cardiopulmonary bypass, a saline-filled latex balloon was inserted
      into the trachea through the tracheal tube. The structures anterior to the
      trachea were imaged with and without the endotracheal balloon. TEE images of the
      proximal aortic arch and innominate artery were classified into three grades
      according to the quality of images: 1, vessel not visible; 2, part of vessel wall
      visible; 3, entire vessel wall visible. Grade 3 was categorized as good
      visualization while grades 1 and 2 were categorized as inadequate. TEE images
      with and without balloon were compared using the Mann-Whitney U-test and Chi
      square analysis. P<0.05 was considered statistically significant. RESULTS: In 20
      patients, 84% had good visualization of proximal aortic arch with presence of
      endotracheal balloon compared with 11% without (P<0.001). A total of 94% had good
      visualization of the proximal innominate artery with presence of endotracheal
      balloon compared with 0% without (P<0.001). CONCLUSIONS: A new 'TEE trans
      tracheal acoustic window' was established by usage of a saline-filled
      endotracheal balloon. This window partially eliminates the TEE blind zone and
      provides improved visualization of the proximal aortic arch and innominate
      artery.

PMID- 16973646
TI  - Low negative predictive value of dobutamine stress echocardiography before
      abdominal aortic surgery.
AB  - BACKGROUND: According to previous studies, a negative dobutamine stress
      echocardiography (DSE) test before major vascular surgery indicates that
      postoperative myocardial necrosis is very unlikely. We believe that the use of
      new cardiac troponin assays which can detect small amounts of myocardial necrosis
      results in a lower DSE negative predictive value for myocardial necrosis.
      METHODS: A total of 418 consecutive patients were screened using the ACC/AHA
      Guideline for Perioperative Cardiovascular Evaluation for Noncardiac Surgery
      before scheduled abdominal aortic surgery. Of these 143 met ACC/AHA criteria for
      non-invasive testing and underwent DSE. Patients with a negative DSE were deemed
      to be fit for surgery. A positive DSE led to a coronary angiogram. DSE was
      negative in 110 (77%) and positive in 33 (23%) patients. Myocardial necrosis was
      monitored up to the third postoperative day by daily cardiac troponin I (cTnI)
      measurement and a daily 12-lead ECG. RESULTS: Coronary angiography showed artery
      stenosis in 27 (84%) of 32 patients with a positive DSE. The negative predictive
      value of DSE for cTnI elevation was 92.7% (95% CI 86.2-96.8%). This was
      significantly lower than the lowest value of negative predictive value for
      myocardial necrosis assessed in previous studies. CONCLUSION: A negative DSE
      prescribed before scheduled aortic surgery according to ACC/AHA guidelines does
      not rule out postoperative myocardial necrosis.

PMID- 16973647
TI  - A prospective, double-blind, randomized trial of caudal block using ropivacaine
      0.2% with or without fentanyl 1 microg kg-1 in children.
AB  - BACKGROUND: It has been reported that ropivacaine produces vasoconstriction in
      contrast to vasodilation produced by bupivacaine. It is possible that additives
      to ropivacaine can provide further analgesic advantages compared with
      bupivacaine. We thus evaluated whether the addition of fentanyl to ropivacaine
      prolonged the duration of analgesia after a single shot caudal block. METHODS: A
      total of 36 children undergoing surgical procedures below the umbilicus were
      randomly allocated to one of two groups: Group F received ropivacaine 0.2%, 1 ml
      kg(-1) with fentanyl 1 microg kg(-1) and Group S received ropivacaine 0.2%, 1 ml
      kg(-1) with saline. The analgesic effect of the caudal block was evaluated using
      the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and sedation was
      assessed using the Steward score at 30 min after extubation and at 1, 2, 4, 6, 12
      and 24 h. The first analgesic requirement time and side-effects in a 24 h period
      were also recorded. RESULTS: There were no differences in characteristics between
      the groups. The end-tidal concentration of sevoflurane at extubation in Group F
      was significantly lower than in Group S. However, there was no significant
      difference in time from discontinuation of the volatile anaesthetics to tracheal
      extubation. No statistical differences were found in the CHEOPS and Steward
      score, and the time to first analgesia. The incidence of postoperative vomiting
      was not significantly different. CONCLUSION: We found that the addition of
      fentanyl 1 mug kg(-1) to ropivacaine 0.2% for caudal analgesia provides no
      further analgesic advantages over ropivacaine 0.2% alone.

PMID- 16973648
TI  - Massachusetts health reform: beauty is in the eye of the beholder.
AB  - The Massachusetts plan to extend health insurance coverage to nearly all of the
      state's residents offers several lessons related to health reform, including the
      following: Bipartisan cooperation is possible; multiple policy mechanisms must be
      employed to achieve meaningful change; the starting point-in terms of the rate of
      uninsurance, the degree of insurance market regulation, and so on-matters; and
      implementation details are critical. In addition to these lessons, we argue that
      objective analysis and a comprehensive framework for evaluating alternative
      policy options are needed for similar reforms to be enacted elsewhere.

PMID- 16973649
TI  - The Massachusetts model: an artful balance.
AB  - The Massachusetts health reform law has attracted national attention for its bold
      vision and its unique combination of tested and innovative policy approaches.
      Despite the law's promise, implementation challenges lie ahead, including
      building and sustaining public and legislative support for the law; ensuring care
      for those who are left out; and containing health care costs. The provisions that
      are most certain of success should provide coverage to 70 percent of the state's
      530,000 uninsured residents. The state's ultimate success in reaching its goal of
      near-universal coverage will depend on how well the state can respond and adjust
      as implementation proceeds.

PMID- 16973650
TI  - Massachusetts reform plus President Bush's tax credits: a national model?
AB  - The Massachusetts health reform offers an important opportunity for a new federal
      state strategy to cover the uninsured. President George Bush's proposed health
      insurance tax credits could be added to the Massachusetts health reform. The
      combined plan would include Medicaid expansions; offer workers affordable
      coverage through competitive insurance markets; and provide federal, state,
      employer, and individual financing. Many other states might be interested in
      similar federal-state partnerships for the forty-five million uninsured
      Americans. Ending the national impasse on coverage needs this kind of bold
      initiative.

PMID- 16973651
TI  - Massachusetts: more mirage than miracle.
AB  - Enactment of the Massachusetts health reform plan stemmed primarily from several
      factors unique to the state. They were augmented by a questionable rationale that
      this latest version of health reform would forestall even greater threats ahead
      to the interests of the state's business community, private insurance
      policyholders, and taxpayers. The plan's foremost achievement involves
      development of a "Connector" mechanism to facilitate pooling and purchasing
      beyond the workplace. However, its successful implementation will be challenged
      by the complexities of enforcing an individual mandate and changing the long
      standing course of an overregulated and high-cost health market.

PMID- 16973652
TI  - Massachusetts health care reform: a look at the issues.
AB  - Massachusetts recently enacted a major health reform that could move the state to
      close to universal health insurance coverage. We describe some of the politics
      behind the legislation and the law's key details. We discuss four major issues
      that the plan would face: (1) a definition of affordability-how much should be
      borne by individuals and how much by government; (2) issues the state will face
      in implementing the Insurance Connector; (3) whether employers will respond by
      dropping coverage; and (4) whether the financing would be adequate, both
      immediately and over time. Massachusetts will face challenges, but it offers a
      model that could be followed elsewhere.

PMID- 16973653
TI  - The third wave of Massachusetts health care access reform.
AB  - In April 2006, Massachusetts passed its third major health care access reform law
      since 1988. This law establishes new structures and requirements that have never
      been attempted by any state. Key features include a shift of federal Medicaid
      dollars from institutional support to individual insurance subsidies,
      establishment of an insurance "Connector," individual and employer
      responsibility, a small-firm and individual insurance market merger, and
      provisions to address racial and ethnic health disparities. Massachusetts will
      engage in a multiyear implementation process. Only after this process is complete
      will the law's significance be clear.

PMID- 16973654
TI  - Comparison of antifungal treatments for murine fusariosis.
AB  - OBJECTIVES: Fusarium solani infections are notoriously difficult to treat. We
      compared the efficacy of polyenes and an echinocandin in treating murine
      fusariosis to identify the optimal therapeutic regimen. METHODS: Neutropenic mice
      infected intravenously with F. solani were treated with amphotericin B (AmB),
      liposomal AmB (LAmB), amphotericin B lipid complex (ABLC), caspofungin acetate or
      a combination of LAmB and caspofungin. Treatment was initiated prior to infection
      (prophylactic therapy), 24 h post-infection (delayed therapy) or 2 days before
      infection and continued for 1 day after (continuous therapy). RESULTS:
      Prophylaxis only with LAmB significantly reduced brain or kidney fungal burden
      compared with placebo. No prophylactic treatment improved survival. LAmB levels
      in the kidneys were higher than ABLC or AmB levels, which were often
      undetectable. In the delayed therapy model, neither polyenes nor caspofungin
      improved survival. In the continuous therapy model, LAmB or LAmB plus caspofungin
      did not improve survival even though they did decrease fungal burden. In
      contrast, continuous caspofungin at 1 but not 5 mg/kg/day improved survival, but
      did not decrease fungal burden. Kidney inflammation and tissue necrosis were
      markedly decreased in mice treated with caspofungin compared with other
      treatments. CONCLUSIONS: These studies demonstrate a dissociation between
      survival and tissue fungal burden during murine fusariosis. Although prophylactic
      LAmB may be useful at reducing tissue fungal burden, polyenes had limited
      survival benefit for active fusariosis. Caspofungin at 1 but not 5 mg/kg/day
      mediated surprising improvements in survival during active fusariosis, despite
      lack of reduction in fungal burden. Further studies are warranted.

PMID- 16973655
TI  - Influence of tannins from Stryphnodendron adstringens on growth and virulence
      factors of Candida albicans.
AB  - OBJECTIVES: The main objective of this work was to investigate the antifungal
      activity of a crude extract, fractions and subfractions from Stryphnodendron
      adstringens (Mart.) Coville, known as 'barbatimao'. METHODS: The growth
      inhibition by 'barbatimao' of 103 isolates of yeasts from vaginal fluid was
      determined using the broth microdilution method. In addition, the effect of the
      most active subfraction on cell surface hydrophobicity (CSH), germ-tube
      formation, budding, ultrastructure and phagocytosis of Candida albicans was
      analysed. Fluconazole and nystatin were used as reference drugs. The cytotoxicity
      of 'barbatimao' to Vero cells, macrophages and red blood cells was assessed. The
      most active subfraction was characterized by mass and 13C NMR spectroscopy.
      RESULTS: Subfraction F2.4 had the best antifungal action at concentrations above
      7.80 mg/L. Its action was similar to nystatin, and only slightly less effective
      than fluconazole. CSH and the capacity for adhering to Vero cells and a glass
      surface were lower in treated yeasts. In addition, the inhibition of formation of
      the germ tube, the increase in the number of buds and changes in the cell wall
      ultrastructure of C. albicans were also demonstrated. 'Barbatimao' extracts
      showed low cytotoxicity to Vero cells, macrophages and red blood cells.
      Subfraction F2.4 is composed of proanthocyanidin polymers of prodelphinidin and
      prorobinetinidin units and gallic acid of molecular weight 2114 Da. CONCLUSIONS:
      The antifungal action of subfraction F2.4 on C. albicans can be attributed to
      condensed tannins. It is considered moderate antifungal activity. These
      properties of 'barbatimao' on the growth of C. albicans, putative virulence
      factors and its low cytotoxicity justify further studies to investigate the
      mechanisms of action and the possible development of a new antifungal agent.

PMID- 16973656
TI  - Central corneal thickness and correlation to optic disc size: a potential link
      for susceptibility to glaucoma.
AB  - AIMS: To evaluate a possible relationship between central corneal thickness (CCT)
      and optic disc area in patients with primary open-angle glaucoma (POAG). METHODS:
      Patients with POAG underwent eye examination, optic disc imaging with the
      Heidelberg Retina Tomograph II (HRT II) and ultrasound corneal pachymetry.
      Exclusion criteria were prior ocular surgery and low-quality HRT II images (HRT
      standard deviation (SD) >50). Pearson's correlation coefficients were calculated
      to assess the associations between CCT and optic disc area. RESULTS: 212 eyes of
      137 patients with POAG were examined. In all, 66 (48%) subjects were women, 104
      (76%) were Caucasian, 26 (19%) African-American and 7 (5%) other races. 72 eyes
      remained after excluding those with prior intraocular surgery and low-quality HRT
      II images. In a univariate analysis of this group, CCT was inversely correlated
      with optic disc surface area (Pearson's correlation coefficient r = -0.284, p =
      0.036, n = 72). Mean (SD) disc area was 2 (0.53) mm(2) (n = 160). Caucasians had
      significantly smaller discs (p<0.001) than other races (Caucasian 1.9 (0.47)
      mm(2) (n = 119), African-Americans 2.4 (0.54) mm(2) (n = 31), other races 2.3
      (0.45) mm(2) (n = 10)). CONCLUSION: CCT is inversely correlated to optic disc
      area. Although thicker corneas have been recognised to cause slight
      overestimation of true intraocular pressure (IOP), they may also indicate the
      presence of a substantially smaller, and thus more robust, optic nerve head.
      People with thinner corneas which slightly underestimate the true IOP may also
      have larger and more deformable optic discs.

PMID- 16973657
TI  - Validity of using vision-related quality of life as a treatment end point in
      intermediate and posterior uveitis.
AB  - AIM: To evaluate the responsiveness of the Vision core module 1 (VCM1) vision
      related quality of life (VR-QOL) questionnaire to changes in visual acuity in
      patients with posterior and intermediate uveitis and to validate its use as a
      clinical end point in uveitis. METHODS: Logarithm of the minimum angle of
      resolution visual acuity and VR-QOL using the VCM1 questionnaire were
      prospectively recorded in 37 patients with active posterior segment intraocular
      inflammation before starting systemic immunosuppression with ciclosporin,
      tacrolimus or the anti-tumour necrosis factor (TNF) agent, p55TNFr-Ig, and again
      3 months later. Spearman analysis was used to correlate improvements in visual
      acuity and VR-QOL between baseline and 3 months. RESULTS: The correlation between
      changes in visual acuity and VR-QOL was moderate to good for the worse eye (r =
      0.47, p = 0.003), but poor for the better eye (r = -0.05, p = 0.91). The
      responsiveness indices effect size and standardised response mean were 0.57 and
      0.59, respectively, showing that the VCM1 questionnaire is moderately responsive
      to immunsosuppressive therapy for active uveitis. CONCLUSION: Changes in VR-QOL
      measured with the VCM1 questionnaire correlated moderately well with changes in
      the worse eye visual acuity, suggesting that the VCM1 is a valid instrument for
      monitoring response to treatment in uveitis.

PMID- 16973658
TI  - Increased levels of pigment epithelium-derived factor in aqueous humor of
      patients with uveitis.
AB  - AIM: To evaluate whether aqueous humor levels of pigment epithelium-derived
      factor (PEDF) are increased in patients with uveitis METHODS: Aqueous humor
      levels of PEDF and tumour necrosis factor alpha (TNFalpha) were determined by
      ELISA in 34 uveitis samples and 9 cataract control samples. RESULTS: Aqueous
      humor PEDF and TNFalpha levels were significantly higher in patients with uveitis
      than in controls (mean (SD) 6.4 (0.8) v 1.3 (0.2) microg/ml and 14.7 (3.8) v 4.2
      (0.4) pg/ml, respectively; p<0.01). A positive correlation between PEDF and
      TNFalpha was found in patients with uveitis (r = 0.40, p<0.01). Furthermore, PEDF
      levels in aqueous humor were increased in proportion to the disease activity of
      uveitis. CONCLUSION: The results show that aqueous humor levels of PEDF are
      increased in patients with uveitis. Our observations suggest that aqueous humor
      levels of PEDF may be increased as a countersystem against inflammation in
      uveitis.

PMID- 16973659
TI  - A prospective randomised trial of different doses of intravitreal triamcinolone
      for diabetic macular oedema.
AB  - OBJECTIVE: To compare the safety and efficacy of different doses of intravitreal
      triamcinolone (ivTA) in treating clinically significant diabetic macular oedema
      (CSMO). METHODS: 63 eyes of 63 patients with CSMO and central foveal thickness
      (CFT) of > or =250 microm on optical coherence tomography were randomised to
      receive 4 mg (n = 23), 6 mg (n = 20) or 8 mg (n = 20) ivTA. Patients were
      followed up for 6 months, and changes in best-corrected visual acuity (BCVA),
      optical coherence tomography CFT, standardised change in macular thickness
      (SCMT), and side effects such as intraocular pressure and cataractogenesis were
      compared between the three groups. RESULTS: After ivTA injection, improvements of
      BCVA and CFT occurred in all groups. The mean BCVA improvement at 6 months was
      significantly higher for the 8 mg group compared with the 4 mg group, with 9.9
      and 3.1 improvement in letters on the Early Treatment of Diabetic Retinopathy
      Study chart, respectively (p = 0.047). The mean SCMT at 6 months for the 4, 6 and
      8 mg groups was 28.7%, 42.3% and 60.5%, respectively (p = 0.06). The proportion
      of eyes with SCMT > or =75% at 6 months was higher in the 8 mg group, but the
      difference failed to reach significance (p = 0.06). Ocular hypertensive responses
      (>21 mm Hg) occurred in 39%, 30% and 55% of eyes in the 4, 6, and 8 mg groups,
      respectively (p = 0.27). CONCLUSIONS: Higher doses of ivTA may prolong the
      duration of visual benefit in diabetic CSMO and seemed to result in more
      sustained reduction in macular oedema. Further studies are warranted to
      investigate the optimum dose of ivTA in treating diabetic CSMO.

PMID- 16973660
TI  - Clinical evaluation of cornea pseudoguttata.
AB  - AIM: To report on cornea pseudoguttata which occurred in 44 eyes from 40
      patients. METHODS: In 3521 consecutive patients seen at a local eye clinic, eyes
      were examined with a slit-lamp biomicroscope in specular illumination. When
      guttate appearance was found, specular microscopy was performed. RESULTS: Cornea
      pseudoguttata was found in 44 eyes of 40 patients (1.1%). All patients had some
      form of anterior-segment ocular diseases, including keratitis (corneal
      infiltration) with contact lens wear (n = 16), epidemic keratoconjunctivitis (n =
      8), corneal epithelial defect (n = 6), superficial punctate keratitis (n = 4),
      corneal foreign body (n = 3), keratitis of unknown causes (n = 3), corneal ulcer
      (n = 2), herpetic keratitis (n = 1), and iritis (n = 1). Six eyes were lost to
      follow-up, but in the remaining 38 eyes, cornea pseudoguttata completely resolved
      as the primary anterior-segment diseases subsided. Specular microscopy, measured
      after resolution of cornea pseudoguttata, showed that corneal endothelial cell
      density was not different between the affected and contralateral healthy eyes.
      CONCLUSION: Cornea pseudoguttata is commonly found in cases with corneal
      infiltration and inflammation. These results indicate that cornea pseudoguttata
      is reversible in its nature and resolves completely without any damage to the
      corneal endothelial cells.

PMID- 16973661
TI  - Glutathione S transferase M1 and T1 genetic polymorphisms are related to the risk
      of primary open-angle glaucoma: a study in a Turkish population.
AB  - BACKGROUND: Genetic factors and oxidative damage have been shown to have a role
      in the development of primary open angle glaucoma (POAG). AIM: To determine the
      effects of genetic polymorphisms of glutathione S transferase (GST)M1 and GSTT1
      on the risk of POAG in a Turkish population. METHODS: Using a multiplex
      polymerase chain reaction (PCR), GSTM1 and GSTT1 gene polymorphisms were analysed
      in 144 patients with POAG and in 121 otherwise healthy controls of similar age.
      RESULTS: The GSTM1 positive genotype and the GSTT1 null genotype had an increased
      risk of developing POAG (p<0.001, OR 2.93, 95% CI 1.66 to 5.20 and OR 4.25, 95%
      CI 2.30 to 7.80, respectively). The risk of glaucoma also increased significantly
      in subjects with a combination of GSTM1 positive and GSTT1 null genotypes
      (p<0.001, OR 3.46, 95% CI 1.64 to 7.38). CONCLUSION: The GSTM1 positive genotype
      and GSTT1 null genotype or the combination of both may be associated with the
      increased risk of development of POAG in the Turkish population.

PMID- 16973662
TI  - Surgery for trachomatous trichiasis: findings from a survey of trichiasis
      surgeons in Tanzania.
AB  - AIMS: To measure the productivity and factors associated with high productivity
      of trichiasis surgeons. METHODS: A standardised, pretested questionnaire was
      posted to all trichiasis surgeons trained in Tanzania at the address listed at
      the time of training, and then followed up by post and telephone with those who
      did not return the form. Questions asked related to place of work, number of
      surgeries carried out, supplies and equipment available, and outreach activities.
      A random selection of high-productivity and low-productivity surgeons was invited
      to a focus group meeting to discuss factors that affected productivity. RESULTS:
      28 of the trained surgeons had died, retired or could not be located. Forms were
      retrieved from 95 others. Productivity (averaged over the past 4 years) was low
      overall, but highly variable. The mean number of surgeries per year was 22.3 (SD
      48.1) and the median was 7. The most important factor associated with higher
      productivity was conducting outreach activities. Conducting outreach was
      associated with having a complete set of instruments and consumables and with
      being able to identify a supervisor. CONCLUSIONS: Redesigning the provision of
      trichiasis surgery (in particular, supervision, support and community
      programmes/outreach) is necessary to ensure that the investment from training is
      used adequately.

PMID- 16973663
TI  - Prevalence of reticular pseudodrusen in age-related macular degeneration with
      newly diagnosed choroidal neovascularisation.
AB  - AIM: To investigate the prevalence of reticular pseudodrusen (RPD) in eyes of
      patients presenting with newly diagnosed choroidal neovascularisation (CNV) in
      age-related macular degeneration (AMD), and to analyse the association between
      RPD, age-related maculopathy (ARM) and AMD. METHOD: Two observational consecutive
      prospective series. In series 1, patients with AMD with newly diagnosed CNV were
      sampled to determine the incidence of RPD. Eyes with and without RPD were
      compared by the Mann-Whitney non-parametric test and Fisher's exact test for age,
      sex of patients, the eye involved and type of CNV. Series 2 comprised 100
      patients referred for fundus photography, fluorescein and/or indocyanine green
      angiography, for whom pictures showed RPD. This second cohort was then selected
      from a larger group of patients. RESULTS: Patients with newly diagnosed CNV in
      series 1 comprised 67 women and 33 men, aged 57-96 years (mean 79.5). CNV was
      "classic" (32 eyes), "occult" (41) or exhibited vascularised pigment epithelial
      detachment (PED, 11), retinal angiomatous proliferation (RAP) with or without PED
      (13), or haemorrhagic or fibrovascular scarring (3). In all, 24 (24%) eyes had
      RPD. The prevalence of RAP was significantly higher in eyes with RPD than in
      those without (p = 0.0128), despite the small number of patients with RAP. In
      series 2, 100 patients with RPD were enrolled in 3 months, and corresponded to 8%
      of the overall cases referred to our centre (Centre Ophtalmologique d'Imagerie et
      de Laser, Paris, France). There were 77 women and 23 men, aged 54-93 years (mean
      79.2). Eyes with RPD (n = 155) usually exhibited signs of ARM or AMD, including
      soft drusen (101 eyes) and/or retinal pigment epithelium abnormalities (70),
      geographical atrophy (27) and/or CNV (61). In both studies, examination of blue
      light fundus pictures was extremely helpful in diagnosing RPD. CONCLUSION: RPD
      have a high prevalence among patients with AMD with newly diagnosed CNV (24% of
      cases). RPD were commonly associated with ARM or AMD. This study suggests that
      eyes with RPD could be classified as a phenotype of ARM.

PMID- 16973664
TI  - Ocular manifestations of Fabry's disease: data from the Fabry Outcome Survey.
AB  - BACKGROUND: Fabry's disease is an X-linked lysosomal storage disorder
      characterised by deficient activity of the enzyme alpha-galactosidase A. AIM: To
      study eye abnormalities in patients with Fabry's disease in the Fabry Outcome
      Survey (FOS). METHODS: This is the largest study of ocular manifestations in
      patients with Fabry's disease. In all, 173 of the 688 patients enrolled in FOS
      underwent a detailed ophthalmic examination, with a special focus on
      abnormalities of the cornea, lens, conjunctival and retinal vessels. RESULTS:
      Cornea verticillata was reported in 76.9% of females and 73.1% of males; vessel
      tortuosity was observed in 21.9% of females and in 48.7% of males. Fabry cataract
      was recorded in 9.8% of females and in 23.1% of males. Cornea verticillata was
      therefore the most frequently reported ophthalmic abnormality in Fabry's disease
      in both hemizygotic males and heterozygotic females. Tortuous conjunctival and
      retinal vessels and Fabry cataract were more frequently found in males than in
      females. Vessel tortuosity was more frequently observed in patients with a higher
      severity score and greater impairment of renal and cardiac function, suggesting
      that it may be associated with a more severe disease. The youngest patient with
      ocular changes was 3 years old. The prevalence of tortuous vessels in males
      increased with age. CONCLUSION: The presence of cornea verticillata is a useful
      aid in the diagnosis of Fabry's disease, as it is often present at the time of
      diagnosis. Vessel tortuosity may have some predictive value for systemic
      involvement.

PMID- 16973665
TI  - Optical coherence tomography of the anterior segment in secondary glaucoma with
      corneal opacity after penetrating keratoplasty.
AB  - AIM: To evaluate secondary glaucoma after penetrating keratoplasty with anterior
      segment optical coherence tomography (OCT). DESIGN: Case series. METHODS: Four
      eyes of four patients with corneal opacity and increased intraocular pressure
      (IOP) were evaluated using high-speed (2000 axial scans/s) OCT at 1.3 microm
      wavelength. Cross-sectional images of the anterior segment were analysed to
      assess the cause of increase in pressure. RESULTS: Slit-lamp evaluation of the
      anterior chamber in all cases was limited by corneal opacity. The OCT imaging
      allowed visualisation of anterior-segment structures behind the opaque corneas.
      Using OCT, iris-intraocular lens adhesion and pupillary block were identified as
      the probable reasons for the increased IOP in one case. Peripheral anterior
      synechiae and angle closure were identified in the three remaining cases. In two
      cases, we found that the tip of the aqueous drainage tube was blocked by
      peripheral anterior synechiae. CONCLUSIONS: OCT is similar to ultrasound in that
      it allows visualisation through opaque corneas. However, OCT has an advantage in
      that it requires neither contact nor immersion. It is a valuable tool for
      evaluating the depth of the anterior chamber angle and the causes of secondary
      angle closure.

PMID- 16973666
TI  - Advanced glycation end product deposits in climatic droplet keratopathy.
AB  - BACKGROUND: Climatic droplet keratopathy (CDK), known as spheroid degeneration of
      the cornea, is one of the most frequent degenerative corneal disorders affecting
      visual function. However, the histochemical nature of the deposits seen in CDK is
      still unclear. AIM: To investigate the pathogenesis of CDK, we investigated the
      immunohistochemical localisation of advanced glycation end products (AGEs) in
      surgical specimens of CDK. METHODS: Immunohistochemical localisation of
      N(epsilon)-(carboxymethyl)-l-lysine (CML), N(epsilon)-(carboxyethyl)-l-lysine
      (CEL), pyrraline, pentosidine and imidazolone was examined in three corneas with
      CDK, six corneas with bullous keratopathy and three corneas without any corneal
      diseases. RESULTS: In all the specimens with CDK, immunoreactivity was strong in
      CML, moderate in pyrraline and pentosidine, and weak in imidazolone.
      Immunoreactivity was absent in CEL. In contrast, no immunoreactivity to CML,
      pyrraline, pentosidine, imidazolone or CEL was detected in corneas with bullous
      keratopathy, or in corneas without any corneal diseases. CONCLUSIONS: CDK is
      caused by an aggregation of AGE-modified proteins. The result is consistent with
      etiological findings that ultraviolet irradiation and ageing, both of which are
      accelerators of AGE formation, are closely related to the development of CDK.

PMID- 16973668
TI  - Performance profile of sodium hyaluronate in patients with lipid tear deficiency:
      randomised, double-blind, controlled, exploratory study.
AB  - AIM: To assess the short-term efficacy of hypotonic 0.18% sodium hyaluronate in
      patients with evaporative tear-sufficient dry eye due to lipid tear deficiency
      (LTD). METHODS: This was a randomised, double-blind, controlled, exploratory
      study. A total of 10 patients with dry eye due to LTD were treated as follows:
      one drop of hypotonic 0.18% sodium hyaluronate in one eye and one drop of
      isotonic 0.3% hydroxypropyl-methylcellulose (HPMC)/0.1% dextran in the other eye.
      Non-invasive tear film break-up time (NIBUT) evaluated by using a tear scope with
      grid pattern and subjective ocular symptoms of dry eye were assessed at 15, 30,
      60 and 90 min after instillation. RESULTS: Both sodium hyaluronate and
      HPMC/dextran caused a significant (p<0.05) improvement in NIBUT and symptoms.
      Mean (SD) NIBUT in the sodium hyaluronate group was 3.2 (1.0), 6.4 (2.8), 5.5
      (1.9), 5.3 (1.3) and 3.9 (1.7) s at 0, 15, 30, 60 and 90 min, respectively,
      compared with 3.6 (1.9), 5.5 (3.2), 5.0 (1.5), 4.4 (2.2) and 3.5 (1.2) s in the
      HPMC/dextran group. However, increase in NIBUT was significantly (p<0.05) greater
      and longer in the sodium hyaluronate group than in the HPMC/dextran group.
      CONCLUSION: Treatment with sodium hyaluronate and HPMC/dextran eye drops is
      useful for treating patients with dry eye due to LTD. However, sodium hyaluronate
      caused a significantly (p<0.05) greater increase in NIBUT values than
      HPMC/dextran in such patients.

PMID- 16973667
TI  - Effect of atorvastatin on ocular blood flow velocities in patients with diabetic
      retinopathy.
AB  - AIM: To investigate blood flow velocities in the ophthalmic and central retinal
      arteries (CRAs) in patients with diabetic retinopathy before and after
      atorvastatin treatment. METHODS: 45 patients with type 2 diabetes were included
      in this double-blind, placebo-controlled study. The patients with diabetes were
      divided into three subgroups: group 1 (n = 15) included patients with non
      proliferative diabetic retinopathy (NPDR); group 2 (n = 15) had patients with
      proliferative diabetic retinopathy (PDR); and group 3 (n = 15; placebo group)
      included 8 patients with NPDR and 7 patients with PDR. The patients in groups 1
      and 2 (atorvastatin group) received 10 mg atorvastatin daily for 10 weeks. Pre
      treatment and post-treatment serum levels of total cholesterol, low-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol and triglyceride
      were recorded before and after treatment. Ocular blood flow velocities of the
      ophthalmic artery and CRA were evaluated by colour Doppler imaging before and
      after treatment in each group. RESULTS: The baseline haemodynamic parameters were
      similar between atorvastatin and placebo groups (p>0.05 for both). Atorvastatin
      significantly decreased serum levels of total cholesterol, low-density
      lipoprotein cholesterol and triglycerides in groups 1 and 2 compared with
      pretreatment levels (p<0.001 for both). The mean peak systolic flow velocities
      (PSVs) of the ophthalmic artery in group 2, and the mean PSV and resistive
      indices of the CRA in groups 1 and 2 decreased significantly after atorvastatin
      treatment (p<0.05 for both), whereas the mean end diastolic flow velocity of the
      ophthalmic artery and CRA did not change (p>0.05). There was no significant
      difference in ocular blood flow velocities in the placebo group (p>0.05).
      CONCLUSION: Atorvastatin may have a role in reducing diabetic retinal
      complications, with improvement in vascular resistance and decrease in the mean
      PSVs of the ophthalmic artery and CRA. However, further studies with large
      numbers of patients are needed to obtain the long-term results of this drug.

PMID- 16973669
TI  - Entrance surface doses to patients undergoing selected diagnostic X-ray
      examinations in Sudan.
AB  - The aim of the study was to evaluate the entrance surface doses (ESDs) to
      patients undergoing selected diagnostic X-ray examinations in major Sudanese
      hospitals. ESD per examination was estimated from X-ray tube output parameters in
      four hospitals comprising eight X-ray units and a sample of 346 radiographs.
      Hospital mean ESDs estimated range from 0.17 to 0.27 mGy for chest AP, 1.04-2.26
      mGy for Skull AP/PA, 0.83-1.32 mGy for Skull LAT, 1.31-1.89 mGy for Pelvis AP,
      1.46-3.33 mGy for Lumbar Spine AP and 2.9-9.9 mGy for Lumbar Spine LAT. With
      exception of chest PA examination at two hospitals, mean ESDs were found to be
      within the established international reference doses. The results are useful to
      national and professional organisations and can be used as a baseline upon which
      future dose measurements may be compared.

PMID- 16973670
TI  - Inhibition of gene amplification in telomerase deficient immortalized mouse
      embryonic fibroblasts.
AB  - Mutations in genes important for the preservation of genome stability can
      increase the frequency of gene amplification, a process relevant to tumor
      development. To investigate whether telomerase, the enzyme deputed to telomere
      maintenance, also plays a role in gene amplification, we studied the
      amplification of the carbamyl-P-synthetase, aspartate transcarbamilase, dihydro
      orotase (CAD) gene in immortalized embryonic fibroblasts derived from telomerase
      knockout mice (mTERC(-/-)) of the first and of the sixth generation. As expected,
      in 9 out of 10 N-(phosphonacetyl)-L-aspartate (PALA) resistant clones derived
      from wild-type cells, CAD was amplified; in contrast, in none of the 30 PALA
      resistant clones isolated from the three mTERC(-/-) cell lines we could detect
      CAD amplification, indicating that, in the absence of telomerase activity, gene
      amplification is inhibited. The causal relationship between mTERC deficiency and
      lack of gene amplification was demonstrated by the restoration of CAD gene
      amplification in two of the three deficient cell lines transfected with mTERC.
      The lack of amplification in mTERC deficient cells could be related to a defect
      in the stabilization of the ends of the amplified chromosomes in the absence of
      telomerase, to a more general effect of telomerase in the regulation of gene
      expression, including genes involved in amplification, or to a possible
      interaction of the telomerase RNA with proteins involved in gene amplification.

PMID- 16973671
TI  - Stochastic modelling of colon cancer: is there a role for genomic instability?
AB  - Three stochastic models of genomic instability recently developed by Little and
      Wright (Math. Biosci., (2003) 183, 111-34), with two, three and five stages, and
      the two-stage genomic instability model of Nowak et al. (Proc. Natl Acad. Sci.
      USA, (2002) 99, 16226-16231) are compared with the four-stage model proposed by
      Luebeck and Moolgavkar (Proc. Natl Acad. Sci. USA, (2002) 99, 15095-15100) that
      does not assume such an instability mechanism. All models are fitted to US colon
      cancer incidence data. The best fitting models are the two-stage model of Nowak
      et al. and the two-stage model of Little and Wright, with the four-stage model of
      Luebeck and Moolgavkar not markedly inferior. The fits of the three-stage and
      five-stage models are somewhat worse (P<0.05), the five-stage model fitting
      particularly poorly (P<0.01). Both optimal genomic instability models predict
      cellular mutation rates that are at least 10 000 times higher after genomic
      destabilization, for both sexes. Therefore, the results of this paper are
      somewhat at variance with those of previous analyses of Little and Wright in
      suggesting that equivalently good fit may be obtained by models that do not
      assume a role for genomic destabilization in the induction of colon cancer as for
      those that do.

PMID- 16973672
TI  - Inhibition of chronic ulcerative colitis associated adenocarcinoma development in
      mice by inositol compounds.
AB  - Chronic inflammation is a well recognized risk factor for cancer and patients
      with long-standing ulcerative colitis (UC) are at an increased risk for
      colorectal carcinoma development. In order to prevent UC associated
      carcinogenesis, we tested the effects of inositol compounds (including inositol
      and hexaphosphate inositol) on UC-associated carcinogenesis in our novel mouse
      model. Female C57BL/6 mice were subjected to long-term, cyclic dextran sulfate
      sodium (DSS) treatment and fed a 2-fold iron-enriched diet. The inositol
      compounds were administered via the drinking fluid. In the DSS-plus-2-fold iron
      positive control group, colorectal adenocarcinoma incidence was 70.6% (24/34
      mice) after 15 cycles of DSS treatment (1 DSS cycle=7 day DSS treatment period
      followed by a 10 day recovery period). Tumor multiplicity was 1.26+/-1.05 and
      tumor volume was 21.4+/-5.2 mm3. Adding 1% inositol, tumor incidence was
      statistically significantly reduced (42%, 9 of 21 mice with tumors), as was tumor
      multiplicity (0.5+/-0.7) and tumor volume (4.2+/-1.9 mm3). Administration of
      hexaphosphate inositol noticeably reduced tumor incidence (50%, 12 mice with
      tumors out of 24 total), tumor multiplicity (0.8+/-0.9) and tumor volume (12.3+/
      4.1 mm3); however, the results were not statistically significant (P>0.05).
      Further mechanistic studies showed that the inhibition of UC-associated
      carcinogenesis by inositol compounds might relate to their function on the
      modulation of macrophage mediated inflammation, nitro-oxidative stress and cell
      proliferation in UC-associated carcinogenesis. This study indicates that inositol
      compounds may have the potential to serve as preventive agents for chronic
      inflammation-carcinogenesis.

PMID- 16973673
TI  - Interferon-beta treatment of cervical keratinocytes naturally infected with human
      papillomavirus 16 episomes promotes rapid reduction in episome numbers and
      emergence of latent integrants.
AB  - Following integration of human papillomavirus (HPV) into the host genome,
      overexpression of the viral oncogenes E6 and E7 requires loss of the
      transcriptional repressor functions of E2. A key step in HPV-related
      carcinogenesis is therefore clearance of residual viral episomes, which encode
      E2. As spontaneous loss of HPV-16 episomes in vitro is associated with increased
      expression of antiviral genes inducible by type I interferon (IFN), we used the
      W12 model to examine the effects of exogenous IFN-beta on cervical keratinocytes
      containing HPV-16 episomes as a result of 'natural' infection in vivo. In
      contrast to studies of cells transfected with HPV-31 or bovine papillomavirus,
      IFN-beta caused rapid reduction in numbers of HPV-16 episomes. This was
      associated with the emergence of cells bearing previously latent integrants, in
      which there was increased expression of E6 and E7. Our data indicate that
      integrated HPV-16 can exist in a minority of cells in a mixed population without
      exerting a selective advantage until episome numbers are reduced. The kinetics of
      cell death and changes in viral transcription and translation that we observed
      support a model where integrants are initially present in cells also containing
      episomes, with generalized episome clearance by IFN-beta resulting in integrant
      de-repression. We conclude that IFN-beta can hasten the transition from episomal
      to integrated HPV-16 in naturally infected cervical keratinocytes. Greater
      emphasis should be placed on episome loss in models of HPV-related
      carcinogenesis. We provide the strongest evidence to date that treating HPV-16
      lesions by inducing an IFN response may cause clinical progression.

PMID- 16973674
TI  - An increased micronucleus frequency in peripheral blood lymphocytes predicts the
      risk of cancer in humans.
AB  - The frequency of micronuclei (MN) in peripheral blood lymphocytes (PBL) is
      extensively used as a biomarker of chromosomal damage and genome stability in
      human populations. Much theoretical evidence has been accumulated supporting the
      causal role of MN induction in cancer development, although prospective cohort
      studies are needed to validate MN as a cancer risk biomarker. A total of 6718
      subjects from of 10 countries, screened in 20 laboratories for MN frequency
      between 1980 and 2002 in ad hoc studies or routine cytogenetic surveillance, were
      selected from the database of the HUman MicroNucleus (HUMN) international
      collaborative project and followed up for cancer incidence or mortality. To
      standardize for the inter-laboratory variability subjects were classified
      according to the percentiles of MN distribution within each laboratory as low,
      medium or high frequency. A significant increase of all cancers incidence was
      found for subjects in the groups with medium (RR=1.84; 95% CI: 1.28-2.66) and
      high MN frequency (RR=1.53; 1.04-2.25). The same groups also showed a decreased
      cancer-free survival, i.e. P=0.001 and P=0.025, respectively. This association
      was present in all national cohorts and for all major cancer sites, especially
      urogenital (RR=2.80; 1.17-6.73) and gastro-intestinal cancers (RR=1.74; 1.01
      4.71). The results from the present study provide preliminary evidence that MN
      frequency in PBL is a predictive biomarker of cancer risk within a population of
      healthy subjects. The current wide-spread use of the MN assay provides a valuable
      opportunity to apply this assay in the planning and validation of cancer
      surveillance and prevention programs.

PMID- 16973675
TI  - The importance of carcinogen dose in chemoprevention studies: quantitative
      interrelationships between, dibenzo[a,l]pyrene dose, chlorophyllin dose, target
      organ DNA adduct biomarkers and final tumor outcome.
AB  - Chlorophyllin (CHL) is a potent antimutagen in vitro, an effective anti
      carcinogen in several animal models, and significantly reduced urinary biomarkers
      of aflatoxin B(1) (AFB(1)) exposure in a human population. Here we report an
      expanded analysis of CHL chemoprevention using the potent environmental
      hydrocarbon dibenzo[a,l]pyrene (DBP). A dose-dose matrix design employed over 12
      000 rainbow trout to evaluate the interrelationships among dietary carcinogen
      dose, anti-carcinogen dose, carcinogen-DNA adduct levels at exposure and eventual
      tumor outcome in two target organs. Included was an evaluation of the
      pharmaceutical CHL preparation (Derifil), used previously in a study of
      individuals chronically exposed to AFB(1). CHL was pre-, co- and post-fed at
      doses of 0-6000 p.p.m. and co-fed with DBP at doses of 0-371.5 p.p.m. for 4
      weeks. This protocol generated a total of 21 dose-dose treatment groups, each
      evaluated with three or more replicates of 100 animals. The DBP-only treatment
      produced dose-responsive increases in liver and stomach DBP-DNA adducts, whereas
      increasing CHL co-treatment doses produced successive inhibition in liver (49
      83%) and stomach (47-75%) adduct levels at each DBP dose examined. The remaining
      8711 trout were necropsied, 10 months later. DBP treatment alone produced a logit
      incidence versus log [DBP] dose-response curve in stomach that was linear; CHL co
      treatment provided dose-dependent tumor inhibition which ranged from 30 to 68%
      and was predictable from the adduct response. The Derifil CHL preparation was
      also found to effectively reduce DNA adduction and final tumor incidence in
      stomach (as well as liver), with a potency compatible with its total chlorin
      content. Liver tumor incidence in the DBP-only groups appeared to plateau near
      60%. At DBP doses of <or=80 p.p.m., increasing CHL doses generally reduced tumor
      incidence and multiplicity consistent with early DNA adducts as biomarkers. At
      225 p.p.m. DBP, however, very high CHL doses were required to reduce tumor
      incidence below the 60% plateau. Apparent tumor multiplicity in liver was neither
      linear nor monotonic with DBP dose, but peaked at 80 p.p.m. DBP and declined at
      225 p.p.m., where it was increased by all but one CHL dose. Consequently, the
      effects of a given CHL dose and the predictivity of DNA adducts as biomarkers
      were highly dependent on carcinogen dose. These results underscore the critical
      importance of establishing carcinogen-end point dose-response relationships in
      chemoprevention studies, and the potential otherwise for misleading
      interpretations in chemoprevention studies carried out solely at high-carcinogen
      dose.

PMID- 16973677
TI  - The making of health:: a reflection on the first 10 years in the life of a
      journal.
AB  - This introduction to the Tenth Anniversary Issue surveys articles that have been
      published in health: since its launch. Reviewing the original aims of the
      journal, the editors discuss some of the main issues that authors have raised,
      both about health and illness. Focusing upon articles that have been published in
      this particular journal, we discuss the way that new medical technologies-
      particularly global ones--have shaped ideas about disease and its treatment, and
      in consequence about what 'good health' should be. Related to the growth in
      medical and other technology--not least the rise of the Internet during the life
      of this journal--is the number of articles that discuss the rights of patients
      and the establishment of what might be termed an 'illness culture'. We conclude
      that there continues to be more to health than it being the background to illness
      or disease, and ask the question: should the 'taken for grantedness' of health be
      taken for granted any longer?

PMID- 16973678
TI  - Health as a meaningful social practice.
AB  - The pursuit of health has become a highly valued activity in modern and
      contemporary life, commanding enormous resources and generating an expansive
      professionalization and commercialization along with attendant goods, services
      and knowledge. Health has also become a focal, signifying practice. As a 'key
      word', health is constructed in relation to social structures and experience and
      systematically articulated with other meanings and practices. Although the
      cogency of health as a practical concept is largely a product of the enormous
      influence of modern medicine, medical conceptions have never been able to contain
      the irrepressible proliferation of meanings associated with health. The
      meaningful - and ideological - practices of health can be illustrated by
      comparing three periods in American culture: (1) the late 19th and early 20th
      century; (2) the 1970s and 1980s; and (3) the first years of the 21st century.

PMID- 16973679
TI  - Health stories as connectors and subjectifiers.
AB  - Health circulates inside bodies, as a condition of cells, tissues and organs, and
      outside bodies as signs. Health stories offer people bits of a subjectivity of
      health: an awareness of what is interior, expressed in signs that are exterior.
      Three genres of health stories are described: technoluxe stories, unbearable
      health stories and strategic health stories. These stories call out to people,
      bidding to be subjectifiers of health. Stories connect people who may become
      patients, providers of health services, health products, images, fears and
      desires. Following Latour, health stories are understood as a form of plug-in:
      resources that provide people with an ability to recognize and connect what was
      disparate.

PMID- 16973680
TI  - Running away with health: the urban marathon and the construction of 'charitable
      bodies'.
AB  - The increase in fundraising through mass-participation running events is
      emblematic of a series of issues pertinent to contemporary conceptualizations of
      health and illness. This increasingly popular spectacle serves as an indicator of
      present-day social relationships and broader cultural and ideological values that
      pertain to health. It highlights contemporary discourses on citizenship; 'active
      citizens' can ostentatiously fulfil their rights and responsibilities by raising
      money for those 'in need'. Involvement in such events comprises an example of the
      current trend for drawing attention to illness, and sharing one's experiences
      with others. We examine these issues through a consideration of charity
      advertisements and offer a fourfold typology of runners in terms of their
      orientations to both mass-participation running and charity. We conclude that
      'charitable bodies' are constructed out of the interrelationships between
      philanthropic institutions, sport and individual performance.

PMID- 16973681
TI  - Health identities: from expert patient to resisting consumer.
AB  - This article explores the formation of 'health identities': embodied
      subjectivities that emerge out of complex psychosocial contexts of reflexive
      modernity, in relation to data on health and illness practices among groups of
      people and patients using medical technologies including weight-loss drugs and
      the erectile dysfunction drug sildenafil (Viagra). We examine a range of health
      identities, from the 'expert patient'--a person who broadly adopts a biomedical
      model of health and illness, to a 'resisting consumer', who fabricates a health
      identity around lay experiential models of health and the body. The understanding
      of health identities is developed within a theoretical framework drawing on
      previous work on body/self and the work of Deleuze and Guattari. It is concluded
      that the constellation of health identities reflects the diversity of relations
      in an industrialized, technology-driven, consumer-oriented and media-saturated
      society.

PMID- 16973682
TI  - The genetic conception of health: is it as radical as claimed?
AB  - The so-called new genetics is widely predicted to radically transform medicine
      and public health and deliver considerable benefits in the future. This article
      argues that, although it is doubtful that many of the promised benefits of
      genetic research will be delivered, an increasingly pervasive genetic worldview
      and expectations about future genetic innovations are profoundly shaping
      conceptions of health and illness and priorities in healthcare. Further, it
      suggests that debates about the normative and justice implications of new genetic
      technologies thus far have been constrained by bioethics discourse, which has
      tended to frame questions narrowly in terms of how best to ensure the protection
      and promotion of the rights and freedoms of the individual. Sociologists and
      other social scientists can help broaden debate in this field by exposing the
      assumptions underlying the genetic conception of health and exploring the
      implications of associated developments.

PMID- 16973683
TI  - Changing conceptions of health and life course concepts.
AB  - Health as a social concept is very important in medical sociology. More
      complicated conceptions of health as a multi-dimensional concept have emphasized
      not only physical health status, but aspects of overall well-being. This article
      continues in the tradition of a multi-dimensional concept of health, but adds in
      the complexity of variation over the life course. As people age, chronic health
      problems become more common. Mobility and sensory limitations also increase. How
      does this impact how people view their health? How do more complicated
      understandings of the life course and variation by social factors link to an
      expanded model of health. This literature review article covers material on
      concepts of health and life course concepts. The concluding portions of the
      article focus on the need to improve measurement, to incorporate diversity
      related to social factors such as gender and race, and to incorporate a broader
      understanding of health problems into conceptions of health across the life
      course.

PMID- 16973684
TI  - ABA regulation of K(+)-permeable channels in maize subsidiary cells.
AB  - An antiparallel-directed potassium transport between subsidiary cells and guard
      cells which form the graminean stomatal complex has been proposed to drive
      stomatal movements in maize. To gain insights into the coordinated shuttling of
      K(+) ions between these cell types during stomatal closure, the effect of ABA on
      the time-dependent K(+) uptake and K(+) release channels as well as on the
      instantaneously activating non-selective cation channels (MgC) was examined in
      subsidiary cells. Patch-clamp studies revealed that ABA did not affect the MgC
      channels but differentially regulated the time-dependent K(+) channels. ABA
      caused a pronounced rise in time-dependent outward-rectifying K(+) currents
      (K(out)) at alkaline pH and decreased inward-rectifying K(+) currents (K(in)) in
      a Ca(2+)-dependent manner. Our results show that the ABA-induced changes in time
      dependent K(in) and K(out) currents from subsidiary cells are very similar to
      those previously described for guard cells. Thus, the direction of K(+) transport
      in subsidiary cells and guard cells during ABA-induced closure does not seem to
      be grounded solely on the cell type-specific ABA regulation of K(+) channels.

PMID- 16973685
TI  - The progressive nature of atrial fibrillation: a rationale for early restoration
      and maintenance of sinus rhythm.
AB  - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia,
      affecting young as well as elderly patients and presenting a major therapeutic
      challenge for clinical cardiologists. Recent research has elucidated the
      progressive nature of AF, including the structural and electrical remodelling
      that may become manifest if normal sinus rhythm is not restored, and the serious
      morbidities associated with long-term disease. The controversy over the merits of
      ventricular rate control vs. the restoration and maintenance of normal sinus
      rhythm in the treatment of AF has been explored in a number of large-scale,
      randomized clinical trials. The results of these trials suggest that whereas the
      two strategies may be equivalent for some patient populations, with both
      approaches requiring accompanying anticoagulation therapy, the restoration and
      maintenance of sinus rhythm provide important haemodynamic as well as subjective
      benefits not afforded by rate control. Although early intervention to limit the
      progression of this arrhythmia is hindered by the limitations of existing anti
      arrhythmic therapies, it is nevertheless a critical goal.

PMID- 16973686
TI  - Does intensity of rate-control influence outcome in atrial fibrillation? An
      analysis of pooled data from the RACE and AFFIRM studies.
AB  - AIMS: The AFFIRM and RACE studies showed that rate control is an acceptable
      treatment strategy for atrial fibrillation (AF). We examined whether strict rate
      control offers benefit over more lenient rate control. METHODS AND RESULTS: We
      compared the outcome of patients enrolled in the rate-control arms of AFFIRM and
      RACE, using data from patients who met a composite of overlapping inclusion and
      exclusion criteria. We evaluated 1091 patients, 874 from AFFIRM and 217 from
      RACE. In AFFIRM, the rate-control strategy aimed for a resting heart rate < or
      =80 bpm and heart rate during daily activity of < or =110 bpm. In RACE, a more
      lenient approach was taken: resting heart rate <100 bpm. Primary endpoint was a
      composite of mortality, cardiovascular hospitalization, and myocardial
      infarction. Mean heart rate across all follow-up visits for patients in AF was
      lower in AFFIRM (76.1 vs. 83.4 bpm). Event-free survival for the occurrence of
      the primary endpoint did not differ (64% in AFFIRM vs. 66% in RACE). Patients
      with mean heart rates during AF within the AFFIRM (< or =80) or RACE (<100)
      criteria had a better outcome than patients with heart rates > or =100 (hazard
      ratios 0.69 and 0.58, respectively, for < or =80 and <100 compared with > or =100
      bpm). CONCLUSION: Stringency of the approach to rate control, based on the
      comparison of the AFFIRM and RACE studies, was not associated with an important
      difference in clinical events.

PMID- 16973687
TI  - Severe keratopathy in paediatric Cogan's syndrome.

PMID- 16973688
TI  - A prospective cohort study of arm pain in primary care and physiotherapy-
      prognostic determinants.
AB  - OBJECTIVE: To investigate outcome and prognostic determinants for arm pain
      presenting to primary care and physiotherapy services. METHODS: Patients with arm
      pain were recruited as they presented to primary care and physiotherapy services,
      and were followed for 12 months. At baseline, they were classified by diagnosis
      using a validated examination schedule. Depression, somatizing tendency, health
      anxiety, fear-avoidance beliefs and chronic pain outside the arm were ascertained
      using standard definitions. Three outcomes were considered: same-site pain during
      the final month of follow-up (continuing pain); pain present on most days of that
      month; and pain present without a break of 7 days over follow-up ('unremitting'
      pain). Associations were explored in multi-level logistic regression models and
      summarized as odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS:
      Altogether, 313 (83%) of 375 subjects completed follow-up, including 53% with
      'continuing' and 24% with 'unremitting' pain. 'Continuing' pain was predicted
      most strongly by male sex (OR 1.9, 95% CI 1.2-3.2) (this association was
      restricted largely to the elbow), higher frequency of pain in the past month at
      baseline (OR 2.5, 95% CI 1.1-5.6), chronic pain at sites outside the arm (ORs 1.6
      2.4 for different sites) and current smoking (OR 3.3, 95% CI 1.6-6.6). There were
      also indications that mental health and fear-avoidance beliefs influenced
      prognosis. Predictors for the other two adverse outcomes were similar.
      CONCLUSION: Arm pain often persists in patients who consult medical services.
      Predictors of persistence include male sex (elbow only), frequency of pain at
      baseline, chronic pain at other sites and smoking.

PMID- 16973689
TI  - Postmortem unenhanced magnetic resonance imaging of myocardial infarction in
      correlation to histological infarction age characterization.
AB  - AIMS: Postmortem magnetic resonance (MRI) imaging is currently evaluated as
      alternative to traditional autopsy and myocardial infarction plays a key role
      therein. The aim of this study is to determine the suitability of postmortem MRI
      in infarction age staging. METHODS AND RESULTS: In eight human forensic corpses
      presenting with a total of 11 myocardial infarcted areas, short-axis,
      transversal, and longitudinal long-axis images (T1, T2, stir, flair) were
      acquired in situ on a 1.5 T system. During subsequent autopsy, the section
      technique was adapted to short-axis images. Histological investigations were
      performed along the entire circumference of the left ventricle to correlate the
      signal alteration in MR to the histological appearance. Two peracute infarctions
      were not detected in MRI and autopsy. Four acute infarcted areas presented with
      decreased signal in necrotic centres and increased signal in marginal myocardial
      regions (T2-weighted). T1-weighted images showed local hyperintensities when
      intramyocardial haemorrhage occurred. Four cases showed subacute infarctions with
      hyperintense regions in T2-weighted images and no signal alteration in T1
      weighted images. Four chronic myocardial infarctions showed distinctively
      decreased signals in all applied sequences. CONCLUSION: Postmortem MRI
      demonstrates myocardial infarction in situ and allows for an infarction age
      estimation based on the signal behaviour.

PMID- 16973690
TI  - Pathology of explanted ASD occluder.

PMID- 16973692
TI  - The effects of face cooling during hyperthermic exercise in man: evidence for an
      integrated thermal, neuroendocrine and behavioural response.
AB  - The present study investigated whether face cooling reduced both the perceived
      exertion (RPE) and prolactin (PRL) release during hyperthermic exercise. Ten, non
      heat-acclimated males (23 +/- 2 years; maximal oxygen consumption, 56 +/- 7 ml
      kg(-1) min(-1) [mean +/- s.d.]) exercised for 40 min on a cycle ergometer at 65%
      of their peak aerobic power, at an ambient temperature of 33 degrees C (27%
      relative humidity) with (FC) and without face cooling as a control (CON). With
      FC, forehead temperature was maintained approximately 6 degrees C lower than CON,
      while other skin sites were similar or slightly warmer in the FC condition.
      Rectal temperature increased by approximately 1.5 degrees C with the same time
      course in both conditions. A relative bradycardia was observed during FC, with
      heart rate approximately 5 beats min(-1) lower than CON (P < 0.05). Mean plasma
      lactate was lower during FC (FC, 5.0 +/- 0.3 mmol l(-1); CON, 5.9 +/- 0.3 mmol l(
      1); P < 0.05) but no differences were observed for plasma glucose, which remained
      constant during exercise. Levels of PRL were maintained at 175 +/- 17 mIU l(-1)
      during exercise for FC, while values for CON increased to a peak of 373 +/- 22
      mIU l(-1) so that towards the end of the exercise, for the same rectal
      temperature, PRL was significantly lower in the FC condition (P < 0.05). Global
      and breathing RPE were reduced but only towards the end of the 40 min of exercise
      during FC, whilst subjective thermal comfort was significantly lower during FC (P
      < 0.05). We confirm the substantial effect that FC has on the secretion of PRL
      during hyperthermic exercise but show that it makes a relatively small
      contribution to the perception of effort when compared to the effect of a cool
      total skin area as occurs with exercise in a thermoneutral environment.

PMID- 16973691
TI  - Relative myotoxic and haemodynamic effects of the beta-agonists fenoterol and
      clenbuterol measured in conscious unrestrained rats.
AB  - The beta(2)-adrenoceptor (beta(2)-AR) agonists clenbuterol and fenoterol have
      similar beneficial effects in animal models of heart failure. However, large
      doses of clenbuterol can induce cardiomyocyte death, and it is not known which of
      these agents has the most favourable therapeutic profile. We have investigated
      the cardiotoxicity of clenbuterol and fenoterol alongside that of isoprenaline,
      and compared their haemodynamic effects. Wistar rats (n = 6 per group) were
      subcutaneously injected with each beta-agonist (0.003-3 mmol kg(-1)) or saline,
      and cardiomyocyte apoptosis was detected by caspase 3 immunohistochemistry. In a
      separate experiment, rats (n = 4) were given equivalent doses to those used in
      the myotoxicity studies, in a randomized cross-over design, and their blood
      pressure recorded via radiotelemetry. Injection of 0.3 mmol kg(-1) fenoterol or
      isoprenaline, but not clenbuterol, induced significant cardiomyocyte apoptosis
      (0.4 +/- 0.05%; P < 0.05). At 3 mmol kg(-1), all agonists induced apoptosis
      (fenoterol, 1.1 +/- 0.1%; isoprenaline, 0.9 +/- 0.8%; and clenbuterol, 0.4 +/-
      0.07%; P < 0.05). beta(1)-Adrenoceptor antagonism (10 mg kg(-1) bisoprolol)
      prevented 92% (P < 0.05) of apoptosis induced by all three agonists, but
      clenbuterol-induced apoptosis could also be prevented by 96% (P < 0.05) by
      beta(2)-AR antagonism (10 mg kg(-1) ICI 118 551). Clenbuterol decreased diastolic
      (1.3- to 1.6-fold; P < 0.05) and systolic blood pressure (1.3-fold; P < 0.05),
      and doses > 0.3 mmol kg(-1) increased heart rate (1.4-fold; P < 0.05). Fenoterol
      increased heart rate (1.2- to 1.4-fold; P < 0.05), and doses > 0.3 mmol kg(-1)
      decreased diastolic blood pressure (1.3-fold; P < 0.05). In conclusion, the
      cardiotoxicity of fenoterol was similar to isoprenaline and greater than
      clenbuterol, and fenoterol had less desirable haemodynamic effects.

PMID- 16973693
TI  - Frequency and pattern dependence of adrenergic and purinergic vasoconstriction in
      rat skeletal muscle arteries.
AB  - Sympathetic nerves fire in bursts followed by brief periods of quiescence.
      Periods of quiescence may be a valuable part of coding for different
      neurotransmitters. We compared adrenergic- and non-adrenergic-mediated
      vasoconstriction with repeating burst patterns versus constant frequency
      stimulation. Seventeen rats were killed, and the femoral arteries dissected out
      and mounted in organ tissue baths at 37 degrees C and pH 7.4. Field stimulation
      was applied to artery rings from five rats at constant frequencies of 2-6 Hz for
      144 impulses. In 12 rats, artery rings were stimulated with two burst pattern
      protocols consisting of repeating pairs, triplets, quadruplets or sextuplets
      performed using either 8 or 30 Hz as the instantaneous frequency for a total of
      144 impulses. All protocols were repeated with the P2 purinergic antagonist
      pyridoxal-phosphate-6-azophenyl-2'4'-disulphonic acid (PPADs; 0.42 m) or the
      alpha(1)-antagonist prazosin (1.59 microM). Tension was decreased by the addition
      of the P2 antagonist PPADs (P < 0.05). Prazosin abolished tension at all constant
      frequencies (P < 0.05). P2 and alpha(1)-antagonism decreased tension with 8 and
      30 Hz burst pattern field stimulation. However, the magnitude of decrease in
      tension with prazosin was less with burst patterns compared to the same average
      constant frequencies (P < 0.05). It appears that P2X receptors and alpha(1)
      receptors in the femoral artery are sensitive to frequency and patterns of
      electrical stimulation.

PMID- 16973694
TI  - Decreased placental amino acid transport and intrauterine growth restriction:
      which is the chicken and which is the egg?

PMID- 16973695
TI  - Cell physiology of cAMP sensor Epac.
AB  - Epac is an acronym for the exchange proteins activated directly by cyclic AMP, a
      family of cAMP-regulated guanine nucleotide exchange factors (cAMPGEFs) that
      mediate protein kinase A (PKA)-independent signal transduction properties of the
      second messenger cAMP. Two variants of Epac exist (Epac1 and Epac2), both of
      which couple cAMP production to the activation of Rap, a small molecular weight
      GTPase of the Ras family. By activating Rap in an Epac-mediated manner, cAMP
      influences diverse cellular processes that include integrin-mediated cell
      adhesion, vascular endothelial cell barrier formation, and cardiac myocyte gap
      junction formation. Recently, the identification of previously unrecognized
      physiological processes regulated by Epac has been made possible by the
      development of Epac-selective cyclic AMP analogues (ESCAs). These cell-permeant
      analogues of cAMP activate both Epac1 and Epac2, whereas they fail to activate
      PKA when used at low concentrations. ESCAs such as 8-pCPT-2'-O-Me-cAMP and 8
      pMeOPT-2'-O-Me-cAMP are reported to alter Na(+), K(+), Ca(2+) and Cl(-) channel
      function, intracellular [Ca(2+)], and Na(+)-H(+) transporter activity in multiple
      cell types. Moreover, new studies examining the actions of ESCAs on neurons,
      pancreatic beta cells, pituitary cells and sperm demonstrate a major role for
      Epac in the stimulation of exocytosis by cAMP. This topical review provides an
      update concerning novel PKA-independent features of cAMP signal transduction that
      are likely to be Epac-mediated. Emphasized is the emerging role of Epac in the
      cAMP-dependent regulation of ion channel function, intracellular Ca(2+)
      signalling, ion transporter activity and exocytosis.

PMID- 16973696
TI  - Depolarization-induced retrograde synaptic inhibition in the mouse cerebellar
      cortex is mediated by 2-arachidonoylglycerol.
AB  - Endocannabinoids acting on CB(1) cannabinoid receptors are involved in short- and
      long-term depression of synaptic transmission. The aim of the present study was
      to determine which endocannabinoid, anandamide or 2-arachidonoylglycerol (2-AG),
      is involved in depolarization-induced suppression of inhibition (DSI) in the
      cerebellar cortex, which is the most widely studied form of short-term
      depression. Depolarization of Purkinje cells in the mouse cerebellum led to an
      increase in intracellular calcium concentration and to suppression of the
      inhibitory input to these neurons (i.e. DSI occurred). Orlistat and RHC80267, two
      blockers of sn-1-diacylglycerol lipase, the enzyme catalysing 2-AG formation,
      abolished DSI by acting downstream of calcium influx. In contrast, DSI occurred
      also in the presence of a phospholipase C inhibitor. Intact operation of the
      calcium-dependent messengers calmodulin and Ca(2+)-calmodulin-dependent protein
      kinase II were necessary for DSI. DSI was potentiated by an inhibitor of the main
      2-AG-degrading enzyme, monoacylglycerol lipase. Interference with the anandamide
      metabolizing enzyme, fatty acid amide hydrolase, did not modify DSI. Thus, three
      kinds of observations identified 2-AG as the endocannabinoid involved in DSI in
      the mouse cerebellum: DSI was abolished by diacylglycerol lipase inhibitors; DSI
      was potentiated by a monoglyceride lipase inhibitor; and DSI was not changed by
      an inhibitor of fatty acid amide hydrolase. Further experiments indicated that 2
      AG is the endocannabinoid mediating short-term retrograde signalling also at
      other synapses: orlistat abolished DSI in the rat cerebellum, DSI in the mouse
      substantia nigra pars reticulata and depolarization-induced suppression of
      excitation in the mouse cerebellum.

PMID- 16973697
TI  - Inactivation of nitric oxide by rat cerebellar slices.
AB  - Nitric oxide (NO) functions as an intercellular messenger throughout the brain.
      For this role to be performed efficiently, there must be a mechanism for
      neutralizing NO, but whether an active biological process exists, or whether NO
      is lost mainly through diffusion is unclear. To investigate this issue, rat
      cerebellar slices were exposed to constant levels of NO and the cGMP generated
      within the slice used as an indicator of NO concentrations therein. NO was about
      1000-fold less potent in slices (EC50, 1 microM) than in separated cells from the
      same tissue (EC50, 1.6 nM), consistent with access of NO to the slice interior
      being greatly hindered by inactivation. Supporting this interpretation,
      immunohistochemical analysis indicated a marked concentration gradient of cGMP
      across the thickness of slices exposed to subsaturating NO concentrations,
      signifying a marked NO gradient. Several known NO-degrading processes, including
      reaction with lipid peroxyl radicals, erythrocytes and superoxide ions, were
      eliminated as contributing factors, indicating a novel mechanism. A diffusion
      inactivation model was used to estimate the kinetics of NO consumption by the
      slices. The best fits to experimental data indicated a Michaelis-Menten-type
      reaction having a Vmax of 1-2 microM s-1 and a Km of around 10 nM. The rates
      predict that inactivation would impose a very short half-life (<10 ms) on NO in
      physiological concentrations (up to 10 nM) and that it would play an important
      role in shaping the NO concentration profiles when it is synthesized by multiple
      nearby sites.

PMID- 16973698
TI  - The glutamate transporter EAAT5 works as a presynaptic receptor in mouse rod
      bipolar cells.
AB  - Membrane neurotransmitter transporters control the concentration of their
      substrate in the synaptic clefts, through the thermodynamic coupling of uptake to
      the movement of Na(+) and other ions. In addition, excitatory amino acid
      transporters (EAAT) have a Cl(-) conductance which is gated by the joint binding
      of Na(+) and glutamate, but thermodynamically uncoupled to the flux of glutamate.
      This conductance is particularly large in the retina-specific EAAT5 isoform. In
      the mouse retina, we located EAAT5 in both cone and rod photoreceptor terminals
      and in axon terminals of rod bipolar cells. In these later cells, application of
      glutamate on the axon terminal evoked a current that reversed at E(Cl), was
      insensitive to bicuculline, TPMPA, strychnine, dl-AP5, CNQX and MCPG, but blocked
      by the glutamate transporter inhibitor dl-tBOA. Furthermore, short
      depolarizations of the bipolar cells evoked a dl-tBOA and Cd(2+)-sensitive
      current whose amplitude was comparable to the glutamate-evoked current. Its
      kinetics indicated that EAAT5 was located close to the glutamate release site.
      For 2 ms depolarizations evoking maximal responses, the EAAT5-mediated current
      carried between 2 and 8 times more charge as an average inhibitory GABA or
      glycine postsynaptic current received spontaneously from amacrine cells, with 10
      mm or 0.5 mm intracellular EGTA, respectively. In conditions for which reciprocal
      inhibition could be monitored, the charge carried by the EAAT5 current was 1.5
      times larger than the one carried by the inhibitory postsynaptic currents
      received from amacrine cells. These results indicate that EAAT5 acts as a major
      inhibitory presynaptic receptor at mammalian rod bipolar cell axon terminals.
      This feedback mechanism could control glutamate release at the ribbon synapses of
      a non-spiking neuron and increase the temporal contrast in the rod photoreceptor
      pathway.

PMID- 16973699
TI  - The influence of inspiratory muscle work history and specific inspiratory muscle
      training upon human limb muscle fatigue.
AB  - The purpose of this study was to assess the influence of the work history of the
      inspiratory muscles upon the fatigue characteristics of the plantar flexors (PF).
      We hypothesized that under conditions where the inspiratory muscle metaboreflex
      has been elicited, PF fatigue would be hastened due to peripheral
      vasoconstriction. Eight volunteers undertook seven test conditions, two of which
      followed 4 week of inspiratory muscle training (IMT). The inspiratory
      metaboreflex was induced by inspiring against a calibrated flow resistor. We
      measured torque and EMG during isometric PF exercise at 85% of maximal voluntary
      contraction (MVC) torque. Supramaximal twitches were superimposed upon MVC
      efforts at 1 min intervals (MVC(TI)); twitch interpolation assessed the level of
      central activation. PF was terminated (T(lim)) when MVC(TI) was <50% of baseline
      MVC. PF T(lim) was significantly shorter than control (9.93 +/- 1.95 min) in the
      presence of a leg cuff inflated to 140 mmHg (4.89 +/- 1.78 min; P = 0.006), as
      well as when PF was preceded immediately by fatiguing inspiratory muscle work
      (6.28 +/- 2.24 min; P = 0.009). Resting the inspiratory muscles for 30 min
      restored the PF T(lim) to control. After 4 weeks, IMT, inspiratory muscle work at
      the same absolute intensity did not influence PF T(lim), but T(lim) was
      significantly shorter at the same relative intensity. The data are the first to
      provide evidence that the inspiratory muscle metaboreflex accelerates the rate of
      calf fatigue during PF, and that IMT attenuates this effect.

PMID- 16973700
TI  - Involvement of intramuscular interstitial cells of Cajal in neuroeffector
      transmission in the gastrointestinal tract.
AB  - Specialized cells known as interstitial cells of Cajal (ICC) are distributed in
      specific locations within the tunica muscularis of the gastrointestinal (GI)
      tract. ICC serve as electrical pacemakers, provide pathways for the active
      propagation of slow waves, are mediators of enteric motor neurotransmission and
      play a role in afferent neural signalling. Morphological studies have provided
      evidence that motor neurotransmission in the GI tract does not occur through
      poorly defined structures between nerves and smooth muscle, but rather via
      specialized synapses that exist between enteric nerve terminals and intramuscular
      ICC or ICC-IM. ICC-IM are coupled to smooth muscle cells via gap junctions and
      post-junctional responses elicited in ICC-IM are conducted to neighbouring smooth
      muscle cells. Electrophysiological studies from the stomachs and sphincters of
      wild-type and mutant animals that lack ICC-IM have provided functional evidence
      for the importance of ICC in cholinergic excitatory and nitrergic inhibitory
      motor neurotransmission. Intraperitoneal injection of animals with Kit
      neutralizing antibody or organ culture of gastrointestinal tissues in the
      presence of neutralizing antibody, which blocks the development and maintenance
      of ICC, has provided further evidence for the role of ICC in enteric motor
      transmission. ICC-IM also generate an ongoing discharge of unitary potentials in
      the gastric fundus and antrum that contributes to the overall excitability of the
      stomach.

PMID- 16973701
TI  - Serotonin potentiates sympathetic responses evoked by spinal NMDA.
AB  - In urethane-chloralose anaesthetized, neuromuscularly blocked, ventilated rats,
      we examined the effects on sympathetic outflow to brown adipose tissue (BAT) of
      separate and simultaneous spinal microinjections of NMDA and serotonin.
      Microinjection of NMDA (12 pmol) into the right T4 spinal intermediolateral
      nucleus (IML) immediately increased ipsilateral brown adipose tissue (BAT)
      sympathetic nerve activity (SNA; peak: +546% of control), BAT thermogenesis (+0.8
      degrees C) and heart rate (+53 beats min-1), whereas microinjection of a lower
      dose of NMDA (1.2 pmol) did not change any of the recorded variables.
      Microinjection of 5-hydroxytryptamine (5-HT, 2 nmol) into the T4 IML increased
      BAT SNA (peak: +342% of control) at a long latency (mean onset: 23 min). The long
      latency 5-HT-evoked increase in BAT SNA was prevented by microinjection of
      methysergide (600 pmol) into the T4 IML. The increases in BAT SNA evoked by T4
      IML microinjections of NMDA (12 pmol) were significantly potentiated (two to
      three times larger than the response to NMDA alone) following T4 IML
      microinjections of 5-HT (100 pmol to 2 nmol, but not 20 pmol). Also,
      microinjection of 5-HT (200 pmol) converted the subthreshold dose of NMDA (1.2
      pmol) into an effective dose for increasing BAT SNA and heart rate. The 5-HT
      mediated potentiation of the increase in BAT SNA evoked by microinjection of NMDA
      into the T4 IML was reversed by microinjection of methysergide (600 pmol) into
      the T4 IML. These results demonstrate that BAT SNA and thermogenesis can be
      driven by activation of spinal excitatory amino acid or 5-HT receptors and that
      concomitant activation of spinal NMDA and 5-HT receptors can act synergistically
      to markedly increase BAT SNA and thermogenesis.

PMID- 16973702
TI  - Beta-adrenergic receptor desensitization in man: insight into post-exercise
      attenuation of cardiac function.
AB  - Desensitization of the beta-adrenoreceptors (beta-AR) may contribute to a post
      exercise reduction in left ventricular (LV) function. However, attenuation of the
      chronotropic and inotropic responses to a beta-AR agonist may depend upon
      alterations in parasympathetic tone. Furthermore, changes in cardiac output and
      LV diastolic function in response to a beta-AR agonist, pre- to post-prolonged
      exercise, remain unclear. Seven trained males (mean+/-s.d., age 27+/-6 years)
      performed 4 h of ergometer rowing. Peak heart rate (HR) and LV systolic and
      diastolic functional responses to incremental isoproterenol (isoprenaline)
      infusion (2, 4 and 6 microg kg min-1) were assessed after vagal blockade
      (glycopyrrolate, 1.2 mg). LV systolic function was assessed by the
      pressure/volume ratio (systolic blood pressure/end systolic volume) and , whilst
      diastolic function was evaluated as peak early and late transmitral filling
      velocities. Following exercise, the pressure/volume ratio decreased by 25%
      (P<0.05), whereas was unchanged (P>0.05). The early/late filling ratio was
      reduced by 36% after exercise, due to an elevation in late LV filling (P<0.01).
      The increase in HR response to isoproterenol infusion was blunted post-exercise
      at both 4 and 6 microg kg min-1 (127+/-7 and 132+/-6 beats min-1) compared with
      pre-exercise (138+/-8 and 141+/-12 beats min-1, P<0.05). Additionally, the
      pressure/volume ratio and were blunted post-exercise in response to isoproterenol
      (P<0.05). In contrast, diastolic function was similar before and after exercise
      during isoproterenol infusion (P>0.05). Desensitization of the beta-AR
      contributes to an attenuated left ventricular systolic but not diastolic function
      following prolonged exercise.

PMID- 16973703
TI  - Cardiovascular and temperature changes in spinal cord injured rats at rest and
      during autonomic dysreflexia.
AB  - In patients with high spinal cord injuries autonomic dysfunction can be
      dangerous, leading to medical complications such as postural hypotension,
      autonomic dysreflexia and temperature disturbance. While animal models have been
      developed to study autonomic dysreflexia, associated temperature changes have not
      been documented. Our aim here was to use radiotelemetry and infrared thermography
      in rodents to record the development of cardiovascular and skin temperature
      changes following complete T4 transection. In adult male Wistar rats (n=5),
      responses were assessed prior to spinal cord injury (intact) and for 6 weeks
      following injury. Statistical analysis by a repeated-measure ANOVA revealed that
      following spinal cord injury (SCI), rats exhibited decreased mean arterial
      pressure (MAP, average decrease of 26 mmHg; P<0.035) and elevated heart rate (HR,
      average increase of 65 bpm, P<0.035) at rest. The basal core body temperature
      following SCI was also significantly lower than intact levels (-0.9 degrees C;
      P<0.0035). Associated with this decreased basal core temperature following SCI
      was an increased skin temperature of the mid-tail and hindpaw (+5.6 and +4.0
      degrees C, respectively; P<0.0003) consistent with decreased cutaneous
      vasoconstrictor tone. Autonomic dysreflexia, in response to a 1 min colorectal
      distension (25 mmHg), was fully developed by 4 weeks after spinal cord
      transection, producing increases in MAP greater than 25 mmHg (P<0.0003). In
      contrast to the tachycardia seen in intact animals in response to colorectal
      distension, SCI animals exhibited bradycardia (P<0.0023). During episodes of
      autonomic dysreflexia mid-tail surface temperature decreased (approximately -1.7
      degrees C, P<0.012), consistent with cutaneous vasoconstriction. This is the
      first study to compare cardiovascular dysfunction with temperature changes
      following spinal cord transection in rats.

PMID- 16973704
TI  - Similar nociceptive afferents mediate psychophysical and electrophysiological
      responses to heat stimulation of glabrous and hairy skin in humans.
AB  - The ability to perceive and withdraw rapidly from noxious environmental stimuli
      is crucial for survival. When heat stimuli are applied to primate hairy skin,
      first pain sensation is mediated by type-II A-fibre nociceptors (II-AMHs). In
      contrast, the reported absence of first pain and II-AMH microneurographical
      responses when heat stimuli are applied to the hand palm has led to the notion
      that II-AMHs are lacking in this primate glabrous skin. The aim of this study was
      to assess the effect of hairy and glabrous skin stimulation on neural
      transmission of nociceptive inputs elicited by different kinds of thermal
      heating. We recorded psychophysical and EEG brain responses to radiant (laser
      evoked potentials, LEPs) and contact heat stimuli (contact heat-evoked
      potentials, CHEPs) delivered to the dorsum and the palm of the hand in normal
      volunteers. Brain responses were analysed at a single-trial level, using an
      automated approach based on multiple linear regression. Laser stimulation of
      hairy and glabrous skin at the same energy elicited remarkably similar
      psychophysical ratings and LEPs. This finding provides strong evidence that first
      pain to heat does exist in glabrous skin, and suggests that similar nociceptive
      afferents, with the physiological properties of II-AMHs, mediate first pain to
      heat stimulation of glabrous and hairy skin in humans. In contrast, when contact
      heat stimuli were employed, a significantly higher nominal temperature had to be
      applied to glabrous skin in order to achieve psychophysical ratings similar to
      those obtained following hairy skin stimulation, and CHEPs following glabrous
      skin stimulation had significantly longer latencies (N2 wave, +25%; P2 wave,
      +24%) and smaller amplitudes (N2 wave, -40%; P2 wave, -44%) than CHEPs following
      hairy skin stimulation. Irrespective of the stimulated territory, CHEPs always
      had significantly longer latencies (hairy skin N2 wave, +75%; P2 wave, +56%) and
      smaller amplitudes (hairy skin N2 wave, -42%; P2 wave, -19%) than LEPs. These
      findings are consistent with the thickness-dependent delay and attenuation of the
      temperature waveform at nociceptor depth when conductive heating is applied, and
      suggest that the previously reported lack of first pain and microneurographical
      II-AMH responses following glabrous skin stimulation could have been the result
      of a search bias consequent to the use of long-wavelength radiant heating (i.e.
      CO(2) laser) as stimulation procedure.

PMID- 16973705
TI  - Heterozygous HIF-1alpha deficiency impairs carotid body-mediated systemic
      responses and reactive oxygen species generation in mice exposed to intermittent
      hypoxia.
AB  - Chronic intermittent hypoxia (CIH) occurs in patients with sleep apnoea and has
      adverse effects on multiple physiological functions. Previous studies have shown
      that reflexes arising from carotid bodies mediate CIH-evoked cardio-respiratory
      responses, and reactive oxygen species (ROS) play important roles in eliciting
      systemic responses to CIH. Very little is known about the molecular mechanisms
      underlying CIH. The transcriptional activator hypoxia-inducible factor-1 (HIF-1)
      mediates a broad range of cellular and systemic responses to hypoxia, and HIF-1
      is activated in cell cultures exposed to IH. In the present study we examined
      whether CIH activates HIF-1 and if so whether it contributes to cardio
      respiratory responses and ROS generation in mice. Experiments were performed on
      male littermate wild-type (WT) and heterozygous (HET) mice partially deficient in
      HIF-1alpha, the O2 regulated subunit of the HIF-1 complex. Both groups of mice
      were exposed to either 10 days of CIH (15 s of hypoxia followed by 5 min of
      normoxia, 9 episodes h-1, 8 h day-1) or to 10 days of 21% O2 (controls). Carotid
      body response to hypoxia was augmented, and acute intermittent hypoxia (AIH)
      induced sensory long-term facilitation (sLTF) of the chemoreceptor activity in
      CIH-exposed WT mice. In striking contrast, hypoxic sensory response was
      unaffected and AIH was ineffective in eliciting sLTF in CIH-exposed HET mice.
      Analysis of cardio-respiratory responses in CIH-exposed WT mice revealed
      augmented hypoxic ventilatory response, LTF of breathing, elevated blood
      pressures and increased plasma noradrenaline. In striking contrast these
      responses were either absent or attenuated in HET mice exposed to CIH. In CIH
      exposed WT mice, ROS were elevated and this response was absent in HET mice.
      Manganese (III) tetrakis(1-methyl-4-pyridyl) porphyrin pentachloride, a potent
      scavenger of superoxide, not only prevented CIH-induced increases in ROS but also
      CIH-evoked HIF-1alpha up-regulation in WT mice. These results indicate that: (a)
      HIF-1 activation is critical for eliciting CIH-induced carotid body-mediated
      cardio-respiratory responses; (b) CIH increases ROS; and (c) the effects of CIH
      involve complex positive interactions between HIF-1 and ROS.

PMID- 16973706
TI  - Exercise-induced inhibition of angiotensin II vasoconstriction in human thigh
      muscle.
AB  - It is well established that metabolic inhibition of adrenergic vasoconstriction
      contributes to the maintenance of adequate perfusion to exercising skeletal
      muscle. However, little is known regarding nonadrenergic vasoconstriction during
      exercise. We tested the hypothesis that a non-adrenergic vasoconstrictor,
      angiotensin II (AngII), would be less sensitive to metabolic inhibition than an
      alpha1-agonist, phenylephrine (PE), in the exercising human thigh. In 11 healthy
      men, femoral blood flow (FBF, ultrasound Doppler and thermodilution) and blood
      pressure were evaluated during wide-ranging doses of intra-arterial (femoral)
      infusions of PE and AngII at rest and during two workloads of steady-state knee
      extensor exercise (7 W and 27 W). At rest, the maximal decrease in femoral artery
      diameter (FAD) during AngII (9.0+/-0.2 to 8.4+/-0.4 mm) was markedly less than
      during PE (9.0+/-0.3 to 5.7+/-0.5 mm), whereas maximal reductions in FBF and
      femoral vascular conductance (FVC) were similar during AngII (FBF: -65+/-6 and
      FVC: -66+/-6%) and PE (-57+/-5 and -59+/-4%). During exercise, FAD was not
      changed by AngII, but moderately decreased by PE. The maximal reductions in FBF
      and FVC were blunted during exercise compared to rest for both AngII (7 W: -28+/
      5 and -40+/-5%; 27 W: -15+/-4% and -29+/-5%) and PE (7 W: -30+/-4 and -37+/-6%;
      27 W: -15+/-2 and -24+/-6%), with no significant differences between drugs. The
      major new findings are (1) an exercise-induced intensity-dependent metabolic
      attenuation of non-adrenergic vasoconstriction in the human leg; and (2)
      functional evidence that AngII-vasoconstriction is predominantly distal, whereas
      alpha1-vasoconstriction is proximal and distal within the muscle vascular bed of
      the human thigh.

PMID- 16973707
TI  - Angiotensin II activates two cation conductances with distinct TRPC1 and TRPC6
      channel properties in rabbit mesenteric artery myocytes.
AB  - Angiotensin II (Ang II) is a potent vasoconstrictor with an important role in
      controlling blood pressure; however, there is little information on cellular
      mechanisms underlying Ang II-evoked vasoconstrictor responses. The aim of the
      present study is to investigate the effect of Ang II on cation conductances in
      freshly dispersed rabbit mesenteric artery myocytes at the single-channel level
      using patch-clamp techniques. In cell-attached patches, bath application of low
      concentrations of Ang II (1 nM) activated cation channel currents (Icat1) with
      conductances states of about 15, 30 and 45 pS. At relatively high concentrations,
      Ang II (100 nM) inhibited Icat1 but evoked another cation channel (Icat2) with a
      conductance of approximately 2 pS. Ang II-evoked Icat1 and Icat2 were inhibited
      by the AT1 receptor antagonist losartan and the phospholipase C (PLC) inhibitor
      U73122. The diacylglycerol (DAG) lipase inhibitor RHC80267 initially induced
      Icat1 which was subsequently inhibited to reveal Icat2. The DAG analogue 1-oleoyl
      2-acetyl-sn-glycerol (1 microM) activated Icat1 and Icat2 but inositol 1,4,5
      trisphosphate did not evoke either conductance. The protein kinase C (PKC)
      inhibitor chelerythrine (3 microM) potentiated Ang II-evoked Icat1 and inhibited
      Icat2 whereas the PKC activator phorbol-12,13-dibutyrate (1 microM) reduced Ang
      II-induced Icat1 but activated Icat2. Moreover in cell-attached patches
      pretreated with chelerythrine, application of 100 nM Ang II activated Icat1.
      These data indicate that PKC inhibits Icat1 but stimulates Icat2. Agents that
      deplete intracellular Ca2+ stores also activated cation channel currents with
      similar properties to Icat2. Bath application of anti-TRPC6 and anti-TRPC1
      antibodies to inside-out patches inhibited Icat1 and Icat2, respectively. Also
      flufenamic acid and zero external Ca2+ concentration, respectively, potentiated
      and reduced Ang II-evoked Icat1. Immunocytochemical studies showed TRPC6 and
      TRPC1 expression with TRPC6 preferentially distributed in the plasma membrane and
      TRPC1 expression located throughout the myocyte. These results indicate that Ang
      II activates two distinct cation conductances in mesenteric artery myocytes by
      stimulation of AT1 receptors linked to PLC. Icat1 is activated by DAG via a PKC
      independent mechanism whereas Icat2 involves DAG acting via a PKC-dependent
      pathway. Higher concentrations of Ang II inhibit Icat1 by activating an
      inhibitory effect of PKC. It is proposed that TRPC6 and TRPC1 channel proteins
      are important components of Ang II-induced Icat1 and Icat2, respectively.

PMID- 16973708
TI  - Fast forward to new genes in mammalian reproduction.
AB  - The study of reproductive genetics in mammals has lagged behind that of simpler
      and more tractable model organisms, such as D. melanogaster, C. elegans and
      various yeast models. Although much valuable information has been generated using
      these organisms, they do not model the genetic and biological complexity of
      mammalian reproduction. Thus, the majority of genes required for gametogenesis in
      mammals remain unidentified. To expand on the existing knowledge of mammalian
      reproductive genetics, we have carried out forward genetic screens in mice to
      identify infertility mutants and the underlying mutant genes. Two different
      approaches were used: mutagenesis of the germline in whole mice, and mutagenesis
      of embryonic stem cells. This was followed by two- or three-generation breeding
      schemes to identify pedigrees segregating infertility mutations, which were then
      phenotypically characterized, genetically mapped, and in some cases, positionally
      cloned. This whole-genome approach has generated a wide collection of mutants
      with defects ranging from problems with germ cell development to abnormal sperm
      morphology. These models have allowed us to study the genetics, as well as the
      physiology, of reproduction in mammals. This review focuses on describing some of
      the genes identified in these screens and the ongoing effort to characterize
      additional mutants.

PMID- 16973709
TI  - Modulation of GABAergic inhibition in the rat superior colliculus by a
      presynaptic group II metabotropic glutamate receptor.
AB  - Previous work has indicated that metabotropic glutamate receptors (mGluRs)
      modulate visual responses of superior colliculus (SC) neurones in vivo in a
      variety of ways, in a manner that can be dependent upon visual stimulus
      properties. How this occurs remains unclear. In this study we aimed to determine
      how activation of mGluR2 and mGluR3 receptors (Group II) might modulate visual
      responses, by using field potential and whole-cell patch clamp recording
      techniques in rat SC slice. Stimulation within the superficial layers of the SC,
      in the presence of ionotropic glutamate receptor antagonists, evoked IPSCs that
      were blocked by bicuculline indicating that they are mediated via GABAA
      receptors. It is likely that these IPSCs were of heterogeneous origin as they
      showed substantial variation in paired-pulse behaviour. Nevertheless, activation
      of Group II mGluRs with the group-selective agonist LY354740 (300 nM, bath
      application) resulted in a reduction of these IPSCs (to 56% of control
      amplitude), and this was associated with a decrease in paired-pulse depression.
      At the same concentration, LY354740 did not reduce the EPSC or field-EPSP evoked
      by stimulation of the retinal input to the SC. The effects of LY354740 on IPSCs
      were not mimicked by the mGluR3-selective agonist N-acetyl-aspartyl-glutamate
      (NAAG, 200-500 microM). Stimulation of IPSCs with trains of impulses (10 at 20
      Hz) in order to mimic natural activation patterns resulted in sequences of IPSCs
      that were reduced in amplitude towards the end of the stimulus train. Application
      of the Group II antagonist LY341495 (100 nM) under these conditions resulted in
      an increase in later IPSCs in a third of neurones tested. These findings indicate
      that mGluR2 (but not mGluR3) can selectively modulate GABAergic inhibition in SC,
      probably via a presynaptic mechanism. Furthermore, these receptors may be
      activated by synaptically released transmitter during patterns of activation
      similar to those seen during visual processing. Thus mGluR2 receptors could have
      a function in activity-dependent modulation of inhibitory processing during
      visual responses.

PMID- 16973710
TI  - What simple and complex cells compute.

PMID- 16973711
TI  - Effects of h1-calponin ablation on the contractile properties of bladder versus
      vascular smooth muscle in mice lacking SM-B myosin.
AB  - The functional significance of smooth muscle-specific h1-calponin up-regulation
      in the smooth muscle contractility of SM-B null mice was studied by generating
      double knockout mice lacking both h1-calponin and SM-B myosin. The double
      knockout mice appear healthy, reproduce well and do not show any smooth muscle
      pathology. Loss of h1-calponin in the SM-B null mice bladder resulted in
      increased maximal shortening velocity (V(max)) and steady-state force generation.
      The force dilatation pressure, which was decreased in the SM-B null mesenteric
      vessels, was restored to wild-type levels in the double knockout vessels. In
      contrast, the half-time to maximal constriction was significantly increased in
      the double knockout vessels similar to that of SM-B null mice and indicating
      decreased shortening velocity in the double knockout vessels. Biochemical
      analyses showed that there is a significant reduction in smooth muscle alpha
      actin levels, whereas h-caldesmon levels are increased in the double knockout
      bladder and mesenteric vessels, suggesting that these changes may also partly
      contribute to the altered contractile function. Taken together, our studies
      suggest that up-regulation of h1-calponin in the SM-B null mice may be necessary
      to maintain a reduced level of cross-bridge cycling over time in the absence of
      SM-B myosin and play an important role in regulating the smooth muscle
      contraction.

PMID- 16973712
TI  - The frequency of human, manual adjustments in balancing an inverted pendulum is
      constrained by intrinsic physiological factors.
AB  - While standing naturally and when manually or pedally balancing an equivalent
      inverted pendulum, the load sways slowly (characteristic unidirectional duration
      approximately 1 s) and the controller, calf muscles or hand, makes more frequent
      adjustments (characteristic unidirectional duration 400 ms). Here we test the
      hypothesis that these durations reflect load properties rather than some
      intrinsic property of the human neuromuscular system. Using a specialized set-up
      mechanically analogous to real standing, subjects manually balanced inverted
      pendulums with different moments of inertia through a compliant spring
      representing the Achilles tendon. The spring bias was controlled by a sensitive
      joystick via a servo motor and accurate visual feedback was provided on an
      oscilloscope. As moment of inertia decreased, inverted pendulum sway size
      increased and it became difficult to sustain successful balance. The mean
      duration of unidirectional balance adjustments did not change. Moreover, the mean
      duration of unidirectional inverted pendulum sway reduced only slightly,
      remaining around 1 s. The simplest explanation is that balance was maintained by
      a process of manual adjustments intrinsically limited to a mean frequency of two
      to three unidirectional adjustments per second corresponding to intermittent
      control observed in manual tracking experiments. Consequently the inverted
      pendulum sway duration, mechanically related to the bias duration, reflects an
      intrinsic constraint of the neuromuscular control system. Given the similar
      durations of sway and muscle adjustments observed in real standing, we postulate
      that the characteristic duration of unidirectional standing sway reflects
      intrinsic intermittent control rather than the inertial properties of the body.

PMID- 16973713
TI  - Auditory mechanotransduction in the absence of functional myosin-XVa.
AB  - In hair cells of all vertebrates, a mechanosensory bundle is formed by
      stereocilia with precisely graded heights. Unconventional myosin-XVa is critical
      for formation of this bundle because it transports whirlin and perhaps other
      molecular components responsible for programmed elongation of stereocilia to the
      stereocilia tips. A tip of a stereocilium is the site of stereocilia growth and
      one of the proposed sites of mechano-electrical transduction. In adult shaker 2
      mice, a mutation that disables the motor function of myosin-XVa results in
      profound deafness and abnormally short stereocilia that lack stereocilia links,
      an indispensable component of mechanotransduction machinery. Therefore, it was
      assumed that myosin-XVa is required for proper formation of the
      mechanotransduction apparatus. Here we show that in young postnatal shaker 2
      mice, abnormally short stereocilia bundles of auditory hair cells have numerous
      stereocilia links and 'wild type' mechano-electrical transduction. We compared
      the mechanotransduction current in auditory hair cells of young normal-hearing
      littermates, myosin-XVa-deficient shaker 2 mice, and whirler mice that have
      similarly short stereocilia but intact myosin-XVa at the stereocilia tips. This
      comparison revealed that the absence of functional myosin-XVa does not disrupt
      adaptation of the mechanotransduction current during sustained bundle deflection.
      Thus, the hair cell mechanotransduction complex forms and functions independently
      from myosin-XVa-based hair bundle morphogenesis.

PMID- 16973715
TI  - Acute distal colitis impairs gastric emptying in rats via an extrinsic neuronal
      reflex pathway involving the pelvic nerve.
AB  - BACKGROUND AND AIMS: Patients with inflammatory bowel disease often present with
      abnormal gut motility away from the inflammatory site. We studied remote motility
      disturbances and their pathophysiology in a rat model of colitis. METHODS:
      Colitis was induced 72 h prior to experiments using trinitrobenzene sulphate
      (TNBS) instillation. Inflammation was verified using histology and
      myeloperoxidase (MPO) measurements. To assess gut motility, we determined gastric
      emptying, distal front and geometric centre (GC) of intestinal transit 30 min
      after intragastric administration of a semiliquid Evans blue solution. The
      effects of hexamethonium (20 mg/kg), capsaicin (125 mg/kg) and pelvic nerve
      section on colitis induced motility changes were evaluated. c-Fos expression was
      studied in the pelvic nerve dorsal root ganglion (DRG) S1. RESULTS: Colitis
      reduced gastric emptying from 38.4 (3.6)% in controls to 22.7 (4.4)% in TNBS
      treated rats in the absence of local gastric inflammation. Colitis had no effect
      on the distal front or on the geometric centre of small intestinal transit.
      Hexamethonium reduced gastric emptying in controls to 26.3 (4.1)% but restored it
      to 35.8 (4.4)% in TNBS treated rats. Capsaicin significantly impaired gastric
      emptying in controls from 33.1 (5.2)% to 9.5 (3.3)% while this effect was less
      pronounced in TNBS treated rats (from 19.2 (2.3)% to 11.5 (3.8)%; NS). In TNBS
      treated rats, pelvic nerve section completely restored gastric emptying from 19.8
      (5.3)% to 52.5 (6.3)% without any effect on gastric emptying in control rats.
      TNBS colitis induced de novo c-Fos expression in the DRG S1. CONCLUSIONS:
      Experimental colitis in rats delays gastric emptying via a neuronal pathway
      involving pelvic afferent nerve hyperactivity.

PMID- 16973716
TI  - Role of BRCA1 and BRCA2 mutations in pancreatic cancer.
AB  - Germline mutations in the tumour suppressor genes breast cancer antigen gene
      (BRCA)1 and BRCA2 have been proven to portend a drastically increased lifetime
      risk of breast and ovarian cancers in the individuals who carry them. A number of
      studies have shown that the third most common cancer associated with these
      mutations is pancreatic cancer. BRCA1/2 mutations are characterised by "allelic"
      or "phenotypic" heterogeneity, in that they demonstrate differing cancer
      expressivity between and within pedigrees that segregate their mutations. If the
      same mutation is present in all our cells, why do some families with a given
      mutation display predominantly breast cancer? Why do other lineages show a
      preponderance of ovarian cancer? And why would some families have members who
      develop mostly or exclusively pancreatic cancer--a cancer that occurs more
      commonly in men and that lacks consistent evidence for a hormonal basis to its
      aetiology--which is clearly the case for breast and ovarian cancer? The answer is
      that other modifying genetic and environmental factors must interact to
      preferentially incite carcinogenesis in one organ over another. We are just
      beginning to elucidate what these factors are.

PMID- 16973717
TI  - Characterisation and transplantation of enteric nervous system progenitor cells.
AB  - AIMS: Enteric nervous system (ENS) progenitor cells have been postulated to be an
      appropriate source of cells for the treatment of Hirschsprung's disease. In order
      for this to be successful, the techniques previously used for the isolation of
      rodent ENS progenitor cells need to be adapted for postnatal human tissue. In
      this paper, we describe a method suitable for the preparation of both mouse and
      human postnatal ENS progenitor cells and assess their transplantation potential.
      METHOD: Single cell suspensions were isolated from 11.5 days post-coitum
      embryonic mouse caecum and postnatal human myenteric plexus. These cells were
      cultured under non-adherent conditions to generate neurospheres which were
      implanted into aganglionic embryonic mouse hindgut explants. Cell proliferation,
      migration and differentiation were observed using immunofluorescence microscopy.
      RESULTS: Neurospheres generated from both mouse and human tissues contained
      proliferating neural crest-derived cells that could be expanded in tissue culture
      to generate both glial cells and neurons. When implanted into aganglionic murine
      gut, cells migrated from the neurospheres using pathways appropriate for cells
      derived from the neural crest, and differentiated to become glia and neurons
      expressing neuronal phenotypic markers characteristic of the ENS including nitric
      oxide synthase and vasoactive intestinal polypeptide. CONCLUSION: We have
      developed a technique for the isolation and expansion of ENS progenitor cells
      from human neonates. These cells have the ability to differentiate into neurons
      and glia when transplanted into aganglionic gut, this demonstration being a
      necessary first step for their autologous transplantation in the treatment of
      Hirschsprung's disease.

PMID- 16973718
TI  - Molecular changes evoked by triethylenetetramine treatment in the extracellular
      matrix of the heart and aorta in diabetic rats.
AB  - Most patients with diabetes die from cardiac or arterial disease, for which there
      are limited therapeutic options. Free Cu(2+) ions are strongly pro-oxidant, and
      chelatable-Cu(II) is increased in the diabetic heart. We reported previously that
      treatment by Cu(II)-selective chelation with triethylenetetramine (TETA) evokes
      elevated urinary Cu(II) in diabetic rats and humans in whom it also improved
      hallmarks of established left ventricular (LV) disease. Here, we treated diabetic
      rats with TETA and evaluated its ability to ameliorate Cu(2+)-mediated LV and
      arterial damage by modifying the expression of molecular targets that included
      transforming growth factor (TGF)-beta1, Smad4, extracellular matrix (ECM)
      proteins, extracellular superoxide dismutase (EC-SOD), and heparan sulfate (HS).
      Eight-weeks of TETA treatment significantly improved cardiac diastolic function
      but not [glucose](plasma) in diabetic animals. LV and aortic mRNAs corresponding
      to TGF-beta1, Smad4, collagen types I, III, and IV, and fibronectin-1, and
      plasminogen activator inhibitor-1, were elevated in untreated diabetic animals
      and normalized after TETA treatment. EC-SOD mRNA and protein, and [HS](tissue)
      were significantly decreased in diabetes and restored by drug treatment.
      Candidate molecular mechanisms by which TETA could ameliorate diabetic cardiac
      and arteriovascular disease include the suppression of an activated TGF-beta/Smad
      signaling pathway that mediates increased ECM gene expression and restoration of
      normal EC-SOD and HS regulation. These findings are relevant to the restoration
      toward normal by TETA treatment of cardiac and arterial structure and function in
      diabetes.

PMID- 16973719
TI  - YM-244769, a novel Na+/Ca2+ exchange inhibitor that preferentially inhibits NCX3,
      efficiently protects against hypoxia/reoxygenation-induced SH-SY5Y neuronal cell
      damage.
AB  - We investigated the pharmacological properties and interaction domains of N-(3
      aminobenzyl)-6-{4-[(3-fluorobenzyl)oxy]phenoxy} nicotinamide (YM-244769), a novel
      potent Na(+)/Ca(2+) exchange (NCX) inhibitor, using various NCX-transfectants and
      neuronal and renal cell lines. YM-244769 preferentially inhibited intracellular
      Na(+)-dependent (45)Ca(2+) uptake via NCX3 (IC(50) = 18 nM); the inhibition was
      3.8- to 5.3-fold greater than for the uptake via NCX1 or NCX2, but it did not
      significantly affect extracellular Na(+)-dependent (45)Ca(2+) efflux via NCX
      isoforms. We searched for interaction domains with YM-244769 by NCX1/NCX3
      chimeric analysis and determined that the alpha-2 region in NCX1 is mostly
      responsible for the differential drug response between NCX1 and NCX3. Further
      cysteine scanning mutagenesis in the alpha-2 region identified that the mutation
      at Gly833 markedly reduced sensitivity to YM-244769. Mutant exchangers that
      display either undetectable or accelerated Na(+)-dependent inactivation, had
      markedly reduced sensitivity or hypersensitivity to YM-244769, respectively. YM
      244769, like 2-[2-[4-(4-nitrobenzyloxyl)phenyl]ethyl]isothiourea methanesulfonate
      (KB-R7943), protected against hypoxia/reoxygenation-induced cell damage in
      neuronal SH-SY5Y cells, which express NCX1 and NCX3, more efficiently than that
      in renal LLC-PK(1) cells, which exclusively express NCX1, whereas 2-[4-(4
      nitrobenzyloxy)benzyl]thiazolidine-4-carboxylic acid ethyl ester (SN-6)
      suppressed renal cell damage to a greater degree than neuronal cell damage. These
      protective potencies consistently correlated well with their inhibitory
      efficacies for the Ca(2+) uptake via NCX isoforms existing in the corresponding
      cell lines. Antisense knockdown of NCX1 and NCX3 in SH-SY5Y cells confirmed that
      NCX3 contributes to the neuronal cell damage more than NCX1. Thus, YM-244769 is
      not only experimentally useful as a NCX inhibitor that preferentially inhibits
      NCX3, but also has therapeutic potential as a new neuroprotective drug.

PMID- 16973720
TI  - Factors determining early pregnancy loss in singleton and multiple implantations.
AB  - BACKGROUND: The incidence of first trimester pregnancy loss is much lower in IVF
      twin pregnancies than in IVF singleton pregnancies. The objective of this study
      was to determine which embryonic and maternal factors contribute to this finding.
      METHODS: Retrospective data analysis of the outcome of 1593 pregnancies after day
      3 double-embryo transfer (DET) after IVF or ICSI treatment. RESULTS: Of 1148
      single implantations at 6 weeks, 936 (81.5%) were ongoing pregnancies. Of 445
      multiple implantations at 6 weeks, 354 (79.6%) were ongoing multiple pregnancies,
      80 (17.9%) were ongoing singleton pregnancies and 11 (2.5%) ended in a
      spontaneous abortion. Total pregnancy loss was 18.5 and 2.5% (P < 0.001) in
      singleton and twin gestations, respectively. Loss per gestational sac was 18.5
      and 11.46% (P < 0.001), respectively. Determinants contributing to the
      continuation of gestation beyond 6 weeks were young maternal age, possibility to
      cryopreserve embryos and short GnRH agonist flare-up stimulation protocol.
      Whereas factors promoting multiple implantation at 6 weeks of gestation were
      young maternal age, high cumulative embryo score (CES), male infertility, long
      stimulation protocol and thick endometrium. CONCLUSIONS: Although multiple
      implantation at 6 weeks is predominantly determined by (morphological) embryo
      quality, the continuation of pregnancy beyond 6 weeks becomes more dependent on
      the combination of genetic and developmental potential of the embryo(s) and an
      optimal uterine milieu.

PMID- 16973721
TI  - Long-term psychological adjustment to IVF/ICSI treatment in women.
AB  - BACKGROUND: The aim of this study was to gain more insight into long-term
      psychological adjustment to IVF in women. METHODS: In a prospective cohort study,
      298 women entering their first IVF treatment cycle (including ICSI) completed
      standardized psychological questionnaires before the start of the treatment, just
      after the last treatment cycle, and 6 months and 3-5 years after the last
      treatment cycle. The main outcome measures were state anxiety, depression and
      mode of adaptation to unsuccessful IVF. RESULTS: Anxiety and depression were
      found at follow-up to return to baseline levels following treatment not resulting
      in a live birth, after an initial increase during treatment. On the contrary,
      treatment resulting in a live birth was found to lead to a more positive long
      term emotional status. Women who focused on new life goals as a mode of
      adaptation 3-5 years after IVF without a live birth showed lower levels of
      anxiety and depression compared with those who persisted in their attempts to get
      pregnant. CONCLUSIONS: Treatment that resulted in a live birth led to more
      positive emotional adjustment. In addition, most women who did not give birth to
      a child after treatment adjusted well psychologically. Positive adjustment was
      related to developing new life goals rather than persisting in attempts to get
      pregnant. Helping women to change life goals after abandoning treatment might
      have beneficial effects on the adaptation process.

PMID- 16973722
TI  - Transgenerational epigenetic imprinting of the male germline by endocrine
      disruptor exposure during gonadal sex determination.
AB  - Embryonic exposure to the endocrine disruptor vinclozolin at the time of gonadal
      sex determination was previously found to promote transgenerational disease
      states. The actions of vinclozolin appear to be due to epigenetic alterations in
      the male germline that are transmitted to subsequent generations. Analysis of the
      transgenerational epigenetic effects on the male germline (i.e. sperm) identified
      25 candidate DNA sequences with altered methylation patterns in the vinclozolin
      generation sperm. These sequences were identified and mapped to specific genes
      and noncoding DNA regions. Bisulfite sequencing was used to confirm the altered
      methylation pattern of 15 of the candidate DNA sequences. Alterations in the
      epigenetic pattern (i.e. methylation) of these genes/DNA sequences were found in
      the F2 and F3 generation germline. Therefore, the reprogramming of the male
      germline involves the induction of new imprinted-like genes/DNA sequences that
      acquire an apparent permanent DNA methylation pattern that is passed at least
      through the paternal allele. The expression pattern of several of the genes
      during embryonic development were found to be altered in the vinclozolin F1 and
      F2 generation testis. A number of the imprinted-like genes/DNA sequences
      identified are associated with epigenetic linked diseases. In summary, an
      endocrine disruptor exposure during embryonic gonadal sex determination was found
      to promote an alteration in the epigenetic (i.e. induction of imprinted-like
      genes/DNA sequences) programming of the male germline, and this is associated
      with the development of transgenerational disease states.

PMID- 16973723
TI  - Regulation of endogenous melanocortin-4 receptor expression and signaling by
      glucocorticoids.
AB  - The melanocortin-4 (MC4) receptor plays a pivotal role in regulating food intake
      and energy expenditure, and obesity results from mutations that interfere with
      the MC4 receptor pathway. We investigated the effect of glucocorticoids on
      endogenous MC4 receptors expressed in GT1-1 cells, an immortalized hypothalamic
      neuronal cell line. Dexamethasone (Dex) caused a 5- to 10-fold increase in the
      cAMP response to the MC4 receptor agonist, NDP-alphaMSH. The stimulatory effect
      of Dex reached a maximum within 24 h and was blocked by the glucocorticoid
      antagonist RU486. This glucocorticoid effect was specific for the MC4 receptor
      and not a result of up-regulation of another component of the cAMP cascade,
      because the response to endogenous beta-adrenergic receptor stimulation was not
      altered by Dex. Dex also potentiated NDP-alphaMSH-mediated ERK1/2 activation.
      After 12 h, Dex caused a 3- to 5-fold increase in [125I]NDP-alphaMSH binding,
      which was maintained for at least 48 h and prevented by RU486. Dex withdrawal
      caused a rapid return of MC4 receptor concentration to the basal level. Dex
      mediated increases in MC4 receptor concentration resulted from a rapid but
      transient increase in MC4 receptor mRNA. This regulation apparently requires
      genomic regulatory sequences because Dex did not increase MC4 receptor expression
      or signaling in CHO cells expressing the MC4 receptor under the control of a
      cytomegalovirus promoter. We conclude that in GT1-1 hypothalamic neurons,
      glucocorticoids increase the amplitude of MC4 receptor signaling. This regulation
      may serve as a control to limit the effects of glucocorticoids on food intake.

PMID- 16973724
TI  - Angiotensin II-mediated protein kinase D activation stimulates aldosterone and
      cortisol secretion in H295R human adrenocortical cells.
AB  - Protein kinases are important mediators in intracellular signaling. Angiotensin
      II is the most important modulator of adrenal zona glomerulosa cell physiology.
      Angiotensin II regulates steroidogenesis and proliferation among many other
      metabolic processes. H295R human adrenal cells are a widely used experimental
      model to study adrenal cell physiology and metabolism. We screened for protein
      kinase expression levels using the Kinetwork system in H295R cells after 3 h
      angiotensin II treatment. Protein kinase D (PKD) was the protein kinase that
      suffers the most dramatic changes. PKD is a member of a new class of
      serine/threonine protein kinases that is activated by phosphorylation. Our
      studies indicated that angiotensin II time- and dose-dependently increased PKD
      phosphorylation, which occurred within 2 min of angiotensin II treatment and at
      concentrations as low as 1 nm. PKD phosphorylation was also dose-dependently
      increased by the PKC activator phorbol 12-myristate 13-acetate. Angiotensin II
      mediated PKD phosphorylation was blocked by several PKC inhibitors. Furthermore,
      PKCepsilon translocation inhibitor peptide decreased angiotensin II-mediated PKD
      phosphorylation, and PKCepsilon down-regulation by RNA interference also
      decreased PKD phosphorylation mediated by angiotensin II. Cotransfection of
      constitutively active PKD mutant constructs up-regulated aldosterone synthase and
      11beta-hydroxylase expression in reporter assays. Constitutively active PKD
      mutants increased aldosterone and cortisol secretion under angiotensin II
      stimulatory conditions. This study reveals that PKD is an intracellular signaling
      mediator of angiotensin II regulation of steroidogenesis in human adrenal cells.
      These data provide new insights into the molecular mechanisms involved in
      angiotensin II-induced physiological and pathophysiological events in adrenal
      cells.

PMID- 16973725
TI  - Normal bone density obtained in the absence of insulin receptor expression in
      bone.
AB  - Type I diabetes is characterized by little or no insulin production and
      hyperglycemic conditions. It is also associated with significant bone loss and
      increased bone marrow adiposity. To examine the role of reduced insulin signaling
      in type I diabetic bone loss without inducing hyperglycemia, we used genetically
      reconstituted insulin receptor knockout mice (IRKO-L1) that are euglycemic as a
      result of human insulin receptor transgene expression in the pancreas, liver, and
      brain. RT-PCR analyses demonstrated undetectable levels of insulin receptor
      expression in IRKO-L1 bone, yet IRKO-L1 bones exhibit similar (and trend toward
      greater) bone density compared with wild-type animals as determined by
      microcomputed tomography. More detailed bone analyses indicated that cortical
      bone area was increased in tibias of IRKO-L1 mice. Osteoblast markers
      (osteocalcin and runx2 mRNA levels) and resorption markers (serum pyridinoline
      levels) were similar in wild-type and IRKO-L1 bones. When marrow adiposity was
      examined, we noticed a decrease in adipocyte number and fatty-acid-binding
      protein 2 expression in IRKO-L1 mice compared with wild-type mice. Bone marrow
      stromal cell cultures obtained from wild-type and IRKO-L1 mice demonstrated
      similar adipogenic and osteogenic potentials, indicating that systemic factors
      likely contribute to differences in marrow adiposity in vivo. Interestingly, IGF
      I receptor mRNA levels were elevated in IRKO-L1 bones, suggesting (in combination
      with hyperinsulinemic conditions) that increased IGF-I receptor signaling may
      represent a compensatory response and contribute to the changes in cortical bone.
      Taken together, these results suggest that reduced insulin receptor signaling in
      bone is not a major factor contributing to bone loss in type I diabetes.

PMID- 16973726
TI  - Endocrine disruptor vinclozolin induced epigenetic transgenerational adult-onset
      disease.
AB  - The fetal basis of adult disease is poorly understood on a molecular level and
      cannot be solely attributed to genetic mutations or a single etiology. Embryonic
      exposure to environmental compounds has been shown to promote various disease
      states or lesions in the first generation (F1). The current study used the
      endocrine disruptor vinclozolin (antiandrogenic compound) in a transient
      embryonic exposure at the time of gonadal sex determination in rats. Adult
      animals from the F1 generation and all subsequent generations examined (F1-F4)
      developed a number of disease states or tissue abnormalities including prostate
      disease, kidney disease, immune system abnormalities, testis abnormalities, and
      tumor development (e.g. breast). In addition, a number of blood abnormalities
      developed including hypercholesterolemia. The incidence or prevalence of these
      transgenerational disease states was high and consistent across all generations
      (F1-F4) and, based on data from a previous study, appears to be due in part to
      epigenetic alterations in the male germ line. The observations demonstrate that
      an environmental compound, endocrine disruptor, can induce transgenerational
      disease states or abnormalities, and this suggests a potential epigenetic
      etiology and molecular basis of adult onset disease.

PMID- 16973727
TI  - Trefoil factors are expressed in human and rat endocrine pancreas: differential
      regulation by growth hormone.
AB  - Trefoil factors (TFFs) 1, 2, and 3 are expressed in mucosal epithelia. TFFs are
      particular abundant in the intestine in which they play a crucial role in
      maintenance and restitution of the epithelium. Because pancreas developmentally
      arises from the primitive foregut, we explored the expression of TFFs in the
      pancreas in man and rat. Immunocytochemical staining of adult human pancreas
      showed abundant TFF3 immunoreactivity in pancreatic islets and some duct cells,
      whereas weak TFF1 and no TFF2 staining were detected. In the islets TFF3
      localized to most insulin and some glucagon and pancreatic polypeptide-producing
      cells. TFF3 immunoreactivity was colocalized with insulin and glucagon in
      distinct cell clusters in human fetal pancreas at wk 14 and in the newborn rat
      pancreas. In isolated human and rat islets, TFF3 and TFF1 mRNA was identified by
      RT-PCR, and TFF3 protein was detected in human pancreas and islets by ELISA.
      Exposure of neonatal rat islets or insulinoma cells to GH, a known beta-cell
      growth factor, resulted in markedly increased TFF3 but decreased TFF1 mRNA
      levels. The effect of GH on TFF3 expression was confirmed by Western blot.
      Culture of neonatal rat islets in the presence of TFF3 resulted in attachment and
      migration of the islet cells, but no effects on proliferation, insulin secretion
      or cytokine-induced apoptosis were seen. These data demonstrate expression of
      TFFs in the endocrine pancreas, but their possible functions remain unknown.

PMID- 16973728
TI  - Sphingosine-1-phosphate modulates both lipolysis and leptin production in
      differentiated rat white adipocytes.
AB  - Sphingosine-1-phosphate (S1P) is a pluripotent lipid mediator that transmits
      signals through a family of G protein-coupled receptors to control diverse
      biological processes. Here, we investigated the effects of S1P on the levels of
      intracellular calcium and cAMP in differentiated rat white adipocytes and two
      important aspects of adipocyte-specific physiology, lipolysis and leptin
      production. In adipocytes, S1P signaling pathway was functionally linked to
      phospholipase C via pertussis-toxin-sensitive G protein. Interestingly, at higher
      S1P concentration (1-30 microM), it also induced cAMP generation in a
      concentration-dependent manner, which was pertussis toxin insensitive and was
      mimicked by dihydro-S1P and sphingosylphosphoryl-choline but not by its related
      metabolites, ceramide and sphingosine, or by its structural analogs, phyto-S1P
      and lysophosphatidic acid. Suramin, a known inhibitor of ligand-receptor
      interactions, reduced S1P-induced cAMP generation by 60% of control, whereas
      forskolin-induced cAMP increase was not affected by treatment with suramin. The
      S1P-induced cAMP generation was functionally linked to cAMP response element
      binding protein phosphorylation. Finally, S1P significantly reduced insulin
      induced mRNA of ob gene and leptin secretion, whereas S1P increased glycerol
      release from adipocytes. Both effects of S1P were reversed by a selective
      adenylyl cyclase inhibitor, SQ22536, without significantly affecting basal
      values. In conclusion, extracellular S1P elicits the elevation of cytosolic Ca2+
      and cAMP with a distinct concentration dependency, and S1P-induced cAMP
      generation may be mediated by S1P-selective receptors rather than intracellular
      targets, and the activated adenylyl cyclase-cAMP signaling pathways subsequently
      increase lipolysis and decrease insulin-induced leptin production in rat white
      adipocytes.

PMID- 16973729
TI  - Hyperphagia alters expression of hypothalamic 5-HT2C and 5-HT1B receptor genes
      and plasma des-acyl ghrelin levels in Ay mice.
AB  - The central melanocortin (MC) pathway is suggested to mediate satiety signaling
      downstream of serotonin (5-HT)2C receptors. 5-HT2C receptor mutant mice consume
      more food, which leads to late-onset obesity and impaired glucose tolerance. Ay
      mice with ectopic expression of the agouti peptide, which leads to a perturbation
      of the central MC pathway, develop obesity and diabetes, associated with low
      levels of plasma total ghrelin. Here, we report that 5-wk-old Ay mice consumed
      more food in association with decreases in levels of plasma des-acyl ghrelin, but
      not active ghrelin, and increases in hypothalamic 5-HT2C and 5-HT1B receptor gene
      expression compared with wild-type mice matched for age and body weight. These
      alterations were also observed in 8-wk-old obese Ay mice. Restricted feeding
      significantly decreased hypothalamic 5-HT2C and 5-HT1B receptor gene expression
      in association with a reversal of the decreases in plasma des-acyl ghrelin levels
      in 5-wk-old Ay mice. Moreover, restricted feeding reduced body weight,
      hyperinsulinemia, and hyperglycemia in association with increases in plasma des
      acyl ghrelin levels in 8-wk-old obese Ay mice. Administration of m
      chlorophenylpiperazine and fenfluramine, both of which induce anorexic effects
      via 5-HT2C receptors and/or 5-HT1B receptors, suppressed food intake in 5- and 8
      wk-old Ay mice, whereas the anorexic effects were attenuated in food-restricted
      Ay mice. These findings suggest that the agouti peptide down-regulates
      hypothalamic 5-HT2C and 5-HT1B receptor gene expression under restricted feeding
      conditions, whereas chronic hyperphagia increases the expression of these genes
      and decreases plasma des-acyl ghrelin levels in Ay mice.

PMID- 16973730
TI  - Androgen receptor in sertoli cell is essential for germ cell nursery and
      junctional complex formation in mouse testes.
AB  - To examine the role of androgen receptor (AR) in Sertoli cells (SC), we used a SC
      specific AR knockout (S-AR-/y) mouse to further evaluate the chronological
      changes of seminiferous tubules and the molecular mechanisms of SC androgen/AR
      signals on spermatogenesis. Testes morphology began changing as early as
      postnatal day (PD) 10.5 in wild-type (WT), but not in S-AR-/y mice. After puberty
      (PD 50), the SC nuclei of WT testes migrated to the basal area of the
      seminiferous epithelium; however, in S-AR-/y testes, SC nuclei were disarranged
      and dislocated. Results from electron microscopy further showed an obvious
      duplication of basal lamina of the seminiferous epithelium in S-AR-/y testes at
      PD 50 compared with WT testes. Using quantitative RT-PCR analyses, the expression
      of SC gene profiles were compared in PD 10.5 testes. In S-AR-/y testes, the
      expression levels of 1) vimentin were significantly increased and laminin alpha5
      was significantly decreased in PD 10.5, which contributed to functional defects
      in cytoskeletons and production of the basement membrane component of SC leading
      to cell morphology deterioration and thus affecting the integrity of seminiferous
      epithelium; 2) claudin-11, occludin, and gelsolin were significantly decreased in
      PD 10.5, which contributed to defects in intact junctional complex formation of
      SC leading to impairment of the integrity of the blood-testis barrier; 3) calcium
      channel, voltage-dependent, P/Q-type, alpha1A subunit; tissue-type plasminogen
      activator; transferrin; and epidermal fatty-acid-binding protein were
      significantly decreased in PD 10.5, which contributed to functional defects in
      production and/or secretion of specific proteases, transport proteins, and
      paracrine factors of SC, leading to impairment of its germ cells' nursery
      functions.

PMID- 16973731
TI  - STD NMR spectroscopy and molecular modeling investigation of the binding of N
      acetylneuraminic acid derivatives to rhesus rotavirus VP8* core.
AB  - The VP8* subunit of rotavirus spike protein VP4 contains a sialic acid (Sia)
      binding domain important for host cell attachment and infection. In this study,
      the binding epitope of the N-acetylneuraminic acid (Neu5Ac) derivatives has been
      characterized by saturation transfer difference (STD) nuclear magnetic resonance
      (NMR) spectroscopy. From this STD NMR data, it is proposed that the VP8* core
      recognizes an identical binding epitope in both methyl alpha-D-N
      acetylneuraminide (Neu5Acalpha2Me) and the disaccharide methyl S-(alpha-D-N
      acetylneuraminosyl)-(2-->6)-6-thio-beta-D-galactopyranoside (Neu5Ac-alpha(2,6)-S
      Galbeta1Me). In the VP8*-disaccharide complex, the Neu5Ac moiety contributes to
      the majority of interaction with the protein, whereas the galactose moiety is
      solvent-exposed. Molecular dynamics calculations of the VP8*-disaccharide complex
      indicated that the galactose moiety is unable to adopt a conformation that is in
      close proximity to the protein surface. STD NMR experiments with methyl 9-O
      acetyl-alpha-D-N-acetylneuraminide (Neu5,9Ac(2)alpha2Me) in complex with rhesus
      rotavirus (RRV) VP8* revealed that both the N-acetamide and 9-O-acetate moieties
      are in close proximity to the Sia-binding domain, with the N-acetamide's methyl
      group being saturated to a larger extent, indicating a closer association with
      the protein. RRV VP8* does not appear to significantly recognize the unsaturated
      Neu5Ac derivative [2-deoxy-2,3-didehydro-D-N-acetylneuraminic acid (Neu5Ac2en)].
      Molecular modeling of the protein-Neu5Ac2en complex indicates that key
      interactions between the protein and the unsaturated Neu5Ac derivative when
      compared with Neu5Acalpha2Me would not be sustained. Neu5Acalpha2Me, Neu5Ac
      alpha(2,6)-S-Galbeta1Me, Neu5,9Ac(2)alpha2Me, and Neu5Ac2en inhibited rotavirus
      infection of MA104 cells by 61%, 35%, 30%, and 0%, respectively, at 10 mM
      concentration. NMR spectroscopic, molecular modeling, and infectivity inhibition
      results are in excellent agreement and provide valuable information for the
      design of inhibitors of rotavirus infection.

PMID- 16973732
TI  - Mice lacking alpha1,3-fucosyltransferase IX demonstrate disappearance of Lewis x
      structure in brain and increased anxiety-like behaviors.
AB  - The 3-fucosyl-N-acetyllactosamine [Lewis x (Le(x)), CD15, SSEA-1] carbohydrate
      structure is expressed on several glycolipids, glycoproteins, and proteoglycans
      of the nervous system and has been implicated in cell-cell recognition, neurite
      outgrowth, and neuronal migration during development. To characterize the
      functional role of Le(x) carbohydrate structure in vivo, we have generated mutant
      mice that lack alpha1,3-fucosyltransferase IX (Fut9(-/-)). Fut9(-/-) mice were
      unable to synthesize the Le(x) structure carried on glycoproteins and glycolipids
      in embryonic and adult brain. However, no obvious pathological differences
      between wild-type and Fut9(-/-) mice were found in brain. In behavioral tests,
      Fut9(-/-) mice exhibited increased anxiety-like responses in dark-light
      preference and in elevated plus maze tests. Immunohistochemical analysis showed
      that the number of calbindin-positive neurons was decreased in the basolateral
      amygdala in Fut9(-/-) mice. These observations indicated that the carbohydrates
      synthesized by Fut9 play critical roles in functional regulations of interneurons
      in the amygdalar subdivisions and suggested a role for the Le(x) structure in
      some aspects of emotional behavior in mice.

PMID- 16973733
TI  - Fucosylation in prokaryotes and eukaryotes.
AB  - Fucosylated carbohydrate structures are involved in a variety of biological and
      pathological processes in eukaryotic organisms including tissue development,
      angiogenesis, fertilization, cell adhesion, inflammation, and tumor metastasis.
      In contrast, fucosylation appears less common in prokaryotic organisms and has
      been suggested to be involved in molecular mimicry, adhesion, colonization, and
      modulating the host immune response. Fucosyltransferases (FucTs), present in both
      eukaryotic and prokaryotic organisms, are the enzymes responsible for the
      catalysis of fucose transfer from donor guanosine-diphosphate fucose to various
      acceptor molecules including oligosaccharides, glycoproteins, and glycolipids. To
      date, several subfamilies of mammalian FucTs have been well characterized; these
      enzymes are therefore delineated and used as models. Non-mammalian FucTs that
      possess different domain construction or display distinctive acceptor substrate
      specificity are highlighted. It is noteworthy that the glycoconjugates from
      plants and schistosomes contain some unusual fucose linkages, suggesting the
      presence of novel FucT subfamilies as yet to be characterized. Despite the very
      low sequence homology, striking functional similarity is exhibited between
      mammalian and Helicobacter pylori alpha1,3/4 FucTs, implying that these enzymes
      likely share a conserved mechanistic and structural basis for fucose transfer;
      such conserved functional features might also exist when comparing other FucT
      subfamilies from different origins. Fucosyltranferases are promising tools used
      in synthesis of fucosylated oligosaccharides and glycoconjugates, which show
      great potential in the treatment of infectious and inflammatory diseases and
      tumor metastasis.

PMID- 16973734
TI  - Transient risk factors for acute traumatic hand injuries: a case-crossover study
      in Hong Kong.
AB  - OBJECTIVES: To identify the remediable transient risk factors of occupational
      hand injuries in Hong Kong in order to guide the development of prevention
      strategies. METHODS: The case-crossover study design was adopted. Study subjects
      were workers with acute hand injuries presenting to the government Occupational
      Medicine Unit for compensation claims within 90 days from the date of injury.
      Detailed information on exposures to specific transient factors during the 60
      minutes prior to the occurrence of the injury, during the same time interval on
      the day prior to the injury, as well as the usual exposure during the past work
      month was obtained through telephone interviews. Both matched-pair interval
      approach and usual frequency approach were adopted to assess the associations
      between transient exposures in the workplace and the short-term risk of
      sustaining a hand injury. RESULTS: A total of 196 injured workers were
      interviewed. The results of the matched-pair interval analysis matched well with
      the results obtained using the usual frequency analysis. Seven significant
      transient risk factors were identified: using malfunctioning equipment/materials,
      using a different work method, performing an unusual work task, working overtime,
      feeling ill, being distracted and rushing, with odds ratios ranging from 10.5 to
      26.0 in the matched-pair interval analysis and relative risks ranging between 8.0
      and 28.3 with the usual frequency analysis. Wearing gloves was found to have an
      insignificant protective effect on the occurrence of hand injury in both
      analyses. CONCLUSIONS: Using the case-crossover study design for acute
      occupational hand injuries, seven transient risk factors that were mostly
      modifiable were identified. It is suggested that workers and their employers
      should increase their awareness of these risk factors, and efforts should be made
      to avoid exposures to these factors by means of engineering and administrative
      controls supplemented by safety education and training.

PMID- 16973735
TI  - Respiratory symptoms and bronchial responsiveness among cleaning and disinfecting
      workers in the food industry.
AB  - OBJECTIVES: To measure the levels of exposure to nitrogen trichloride (NCl3) and
      aldehydes among cleaning and disinfecting workers in the atmosphere of food
      industry plants during cleaning and disinfecting operations, and to examine how
      they relate to irritant and chronic respiratory symptoms-which are indices of
      pulmonary function-and bronchial hyperresponsiveness (BHR) to methacholine.
      METHODS: 175 exposed workers (M = 149; F = 26) recruited from 17 enterprises of
      the food industry (8 cattle, pig, and ovine slaughterhouses, 8 fowl
      slaughterhouses, and 1 catering firm) and 70 non-exposed workers (M = 52; F = 18)
      were examined. Concentration levels of NCl3 and aldhehydes were measured by
      personal sampling. Symptoms were assessed by means of a questionnaire and the
      methacholine bronchial challenge (MBC) test using an abbreviated method. Subjects
      were labelled MBC+ if forced expiratory volume in one second (FEV1) fell by 20%
      or more. The linear dose-response slope (DRS) was calculated as the percentage
      fall in FEV1 at last dose divided by the total dose administered. RESULTS: 277
      air samples were taken in the 17 food industry plants. For a given plant and in a
      given workshop, the actual concentrations of chloramines, aldehydes, and
      quaternary ammonium compounds were measured with personal samplers during the
      different steps of the procedures. For each cleaner, a total exposure index Sigma
      was calculated. A statistically significant concentration-response relationship
      was found between eye, nasal, and throat symptoms of irritation--but not chronic
      respiratory symptoms--and exposure levels or exposure duration. No relation was
      found between BHR and exposure. CONCLUSIONS: These data show that cleaning and
      disinfecting workers in the food industry are at risk of developing eye, nasal,
      and throat irritation symptoms. Although NCl3 exposure does not seem to carry a
      risk of developing permanent BHR, the possibility of transient BHR cannot be
      ruled out entirely.

PMID- 16973736
TI  - Do ambient noise exposure levels predict hearing loss in a modern industrial
      cohort?
AB  - BACKGROUND: Much of what is known about the exposure-response relationship
      between occupational noise exposures and hearing loss comes from cross-sectional
      studies conducted before the widespread implementation of workplace hearing
      conservation programmes. Little is known about the current relationship of
      ambient noise exposure measurements to hearing loss risk. AIM: To examine the
      relationship between rates of high frequency hearing loss and measured levels of
      noise exposure in a modern industrial workforce. METHODS: Ten-year hearing loss
      rates were determined for 6217 employees of an aluminium manufacturing company.
      Industrial hygiene and human resources records allowed for reconstruction of
      individual noise exposures. Hearing loss rates were compared to ANSI 3.44
      predictions based on age and noise exposure. Associations between hearing loss,
      noise exposure, and covariate risk factors were assessed using multivariate
      regression. RESULTS: Workers in higher ambient noise jobs tended to experience
      less high frequency hearing loss than co-workers exposed at lower noise levels.
      This trend was also seen in stratified analyses of white males and non-hunters.
      At higher noise exposure levels, the magnitude of hearing loss was less than
      predicted by ANSI 3.44 formulae. There was no indication that a healthy worker
      effect could explain these findings. The majority of 10 dB standard threshold
      shifts (STS) occurred in workers whose calculated ambient noise exposures were
      less than or equal to 85 dBA. CONCLUSIONS: In this modern industrial cohort,
      hearing conservation efforts appear to be reducing hearing loss rates, especially
      at higher ambient noise levels. This could be related to differential use of
      hearing protection. The greatest burden of preventable occupational hearing loss
      was found in workers whose noise exposure averaged 85 dBA or less. To further
      reduce rates of occupational hearing loss, hearing conservation programmes may
      require innovative approaches targeting workers with noise exposures close to 85
      dBA.

PMID- 16973737
TI  - Mortality from non-malignant respiratory diseases among people with silicosis in
      Hong Kong: exposure-response analyses for exposure to silica dust.
AB  - OBJECTIVES: To examine the exposure-response relationships between various
      indices of exposure to silica dust and the mortality from non-malignant
      respiratory diseases (NMRDs) or chronic obstructive pulmonary diseases (COPDs)
      among a cohort of workers with silicosis in Hong Kong. METHODS: The
      concentrations of respirable silica dust were assigned to each industry and job
      task according to historical industrial hygiene measurements documented
      previously in Hong Kong. Exposure indices included cumulative dust exposure (CDE)
      and mean dust concentration (MDC). Penalised smoothing spline models were used as
      a preliminary step to detect outliers and guide further analyses. Multiple Cox's
      proportional hazard models were used to estimate the dust effects on the risk of
      mortality from NMRDs or COPDs after truncating the highest exposures. RESULTS:
      371 of the 853 (43.49%) deaths occurring among 2789 workers with silicosis during
      1981-99 were from NMRDs, and 101 (27.22%) NMRDs were COPDs. Multiple Cox's
      proportional hazard models showed that CDE (p = 0.009) and MDC (p<0.001) were
      significantly associated only with NMRD mortality. Subgroup analysis showed that
      deaths from NMRDs (p<0.01) and COPDs (p<0.05) were significantly associated with
      both CDE and MDC among underground caisson workers and among those ever employed
      in other occupations with high exposure to silica dust. No exposure-response
      relationship was observed for surface construction workers with low exposures. A
      clear upward trend for both NMRDs and COPDs mortality was found with increasing
      severity of radiological silicosis. CONCLUSION: This study documented an exposure
      response relationship between exposure to silica dust and the risk of death from
      NMRDs or COPDs among workers with silicosis, except for surface construction
      workers with low exposures. The risk of mortality from NMRDs increased
      significantly with the progression of International Labor Organization
      categories, independent of dust effects.

PMID- 16973738
TI  - Potential of ultrasonography for epidemiological study of work-related wrist
      tenosynovitis.
AB  - OBJECTIVE: To explore the possible role of ultrasonography in case definitions
      for epidemiological studies of work-related wrist tenosynovitis. METHODS:
      Clinical and ultrasonography (7.5 MHz linear probe) data systematically collected
      from meat workers (n = 128) with biomechanical exposure characterisation were
      analysed. The diagnostic accuracy of different combinations of potentially
      relevant ultrasonography findings (nonhomogeneity, thickening and anechoic halo)
      was evaluated using symptomatology as a reference standard. The concordance
      between ultrasonography findings and symptoms was then analysed. RESULTS:
      Analysis of wrist biomechanical exposure was suggestive of increased prevalence
      of musculoskeletal disorders. Using symptoms as a reference standard, each of the
      three ultrasonography findings (and their combinations) showed good specificity
      (> or =85%) accompanied by low sensitivity (<60%); the positive likelihood ratio
      for at least two findings was 4.1. kappa Values (95% confidence intervals)
      between symptoms and different sets of ultrasonography findings were as follows:
      for non-homogeneity, kappa = 0.31 (0.19 to 0.43); at least one finding, kappa =
      0.28 (0.16 to 0.40); at least two findings, kappa = 0.32 (0.20 to 0.44); all
      p<0.01. CONCLUSION: The use of ultrasonography in symptomatic subjects could
      contribute to a more specific epidemiological case definition of wrist
      tenosynovitis. The results of this study could help orient future research in
      this direction.

PMID- 16973739
TI  - Interventions for the prevention and management of neck/upper extremity
      musculoskeletal conditions: a systematic review.
AB  - Considered from medical, social or economic perspectives, the cost of
      musculoskeletal injuries experienced in the workplace is substantial, and there
      is a need to identify the most efficacious interventions for their effective
      prevention, management and rehabilitation. Previous reviews have highlighted the
      limited number of studies that focus on upper extremity intervention programmes.
      The aim of this study was to evaluate the findings of primary, secondary and/or
      tertiary intervention studies for neck/upper extremity conditions undertaken
      between 1999 and 2004 and to compare these results with those of previous
      reviews. Relevant studies were retrieved through the use of a systematic approach
      to literature searching and evaluated using a standardised tool. Evidence was
      then classified according to a "pattern of evidence" approach. Studies were
      categorised into subgroups depending on the type of intervention: mechanical
      exposure interventions; production systems/organisational culture interventions
      and modifier interventions. 31 intervention studies met the inclusion criteria.
      The findings provided evidence to support the use of some mechanical and modifier
      interventions as approaches for preventing and managing neck/upper extremity
      musculoskeletal conditions and fibromyalgia. Evidence to support the benefits of
      production systems/organisational culture interventions was found to be lacking.
      This review identified no single-dimensional or multi-dimensional strategy for
      intervention that was considered effective across occupational settings. There is
      limited information to support the establishment of evidence-based guidelines
      applicable to a number of industrial sectors.

PMID- 16973740
TI  - The crystal structure of human IRE1 luminal domain reveals a conserved
      dimerization interface required for activation of the unfolded protein response.
AB  - The unfolded protein response (UPR) is an evolutionarily conserved mechanism by
      which all eukaryotic cells adapt to the accumulation of unfolded proteins in the
      endoplasmic reticulum (ER). Inositol-requiring kinase 1 (IRE1) and PKR-related ER
      kinase (PERK) are two type I transmembrane ER-localized protein kinase receptors
      that signal the UPR through a process that involves homodimerization and
      autophosphorylation. To elucidate the molecular basis of the ER transmembrane
      signaling event, we determined the x-ray crystal structure of the luminal domain
      of human IRE1alpha. The monomer of the luminal domain comprises a unique fold of
      a triangular assembly of beta-sheet clusters. Structural analysis identified an
      extensive dimerization interface stabilized by hydrogen bonds and hydrophobic
      interactions. Dimerization creates an MHC-like groove at the interface. However,
      because this groove is too narrow for peptide binding and the purified luminal
      domain forms high-affinity dimers in vitro, peptide binding to this groove is not
      required for dimerization. Consistent with our structural observations, mutations
      that disrupt the dimerization interface produced IRE1alpha molecules that failed
      to either dimerize or activate the UPR upon ER stress. In addition, mutations in
      a structurally homologous region within PERK also prevented dimerization. Our
      structural, biochemical, and functional studies in vivo altogether demonstrate
      that IRE1 and PERK have conserved a common molecular interface necessary and
      sufficient for dimerization and UPR signaling.

PMID- 16973741
TI  - A small-molecule inhibitor of type III secretion inhibits different stages of the
      infectious cycle of Chlamydia trachomatis.
AB  - The intracellular pathogen Chlamydia trachomatis possesses a type III secretion
      (TTS) system believed to deliver a series of effector proteins into the inclusion
      membrane (Inc-proteins) as well as into the host cytosol with perceived
      consequences for the pathogenicity of this common venereal pathogen. Recently,
      small molecules were shown to block the TTS system of Yersinia
      pseudotuberculosis. Here, we show that one of these compounds, INP0400, inhibits
      intracellular replication and infectivity of C. trachomatis at micromolar
      concentrations resulting in small inclusion bodies frequently containing only one
      or a few reticulate bodies (RBs). INP0400, at high concentration, given at the
      time of infection, partially blocked entry of elementary bodies into host cells.
      Early treatment inhibited the localization of the mammalian protein 14-3-3beta to
      the inclusions, indicative of absence of the early induced TTS effector IncG from
      the inclusion membrane. Treatment with INP0400 during chlamydial mid-cycle
      prevented secretion of the TTS effector IncA and homotypic vesicular fusions
      mediated by this protein. INP0400 given during the late phase resulted in the
      detachment of RBs from the inclusion membrane concomitant with an inhibition of
      RB to elementary body conversion causing a marked decrease in infectivity.

PMID- 16973742
TI  - Cropland expansion changes deforestation dynamics in the southern Brazilian
      Amazon.
AB  - Intensive mechanized agriculture in the Brazilian Amazon grew by >3.6 million
      hectares (ha) during 2001-2004. Whether this cropland expansion resulted from
      intensified use of land previously cleared for cattle ranching or new
      deforestation has not been quantified and has major implications for future
      deforestation dynamics, carbon fluxes, forest fragmentation, and other ecosystem
      services. We combine deforestation maps, field surveys, and satellite-based
      information on vegetation phenology to characterize the fate of large (>25-ha)
      clearings as cropland, cattle pasture, or regrowing forest in the years after
      initial clearing in Mato Grosso, the Brazilian state with the highest
      deforestation rate and soybean production since 2001. Statewide, direct
      conversion of forest to cropland totaled >540,000 ha during 2001-2004, peaking at
      23% of 2003 annual deforestation. Cropland deforestation averaged twice the size
      of clearings for pasture (mean sizes, 333 and 143 ha, respectively), and
      conversion occurred rapidly; >90% of clearings for cropland were planted in the
      first year after deforestation. Area deforested for cropland and mean annual
      soybean price in the year of forest clearing were directly correlated (R(2) =
      0.72), suggesting that deforestation rates could return to higher levels seen in
      2003-2004 with a rebound of crop prices in international markets. Pasture remains
      the dominant land use after forest clearing in Mato Grosso, but the growing
      importance of larger and faster conversion of forest to cropland defines a new
      paradigm of forest loss in Amazonia and refutes the claim that agricultural
      intensification does not lead to new deforestation.

PMID- 16973743
TI  - Self-assembly of receptor/signaling complexes in bacterial chemotaxis.
AB  - Escherichia coli chemotaxis is mediated by membrane receptor/histidine kinase
      signaling complexes. Fusing the cytoplasmic domain of the aspartate receptor,
      Tar, to a leucine zipper dimerization domain produces a hybrid, lzTar(C), that
      forms soluble complexes with CheA and CheW. The three-dimensional reconstruction
      of these complexes was different from that anticipated based solely on structures
      of the isolated components. We found that analogous complexes self-assembled with
      a monomeric cytoplasmic domain fragment of the serine receptor without the
      leucine zipper dimerization domain. These complexes have essentially the same
      size, composition, and architecture as those formed from lzTar(C). Thus, the
      organization of these receptor/signaling complexes is determined by conserved
      interactions between the constituent chemotaxis proteins and may represent the
      active form in vivo. To understand this structure in its cellular context, we
      propose a model involving parallel membrane segments in receptor-mediated CheA
      activation in vivo.

PMID- 16973744
TI  - The herpesvirus glycoproteins B and H.L are sequentially recruited to the
      receptor-bound gD to effect membrane fusion at virus entry.
AB  - Four glycoproteins (gD, gB, gH, and gL) are required for herpes simplex virus
      entry into the cell or for cell-cell fusion in transfected cells. gD serves as
      the receptor-binding glycoprotein and as the trigger of fusion; the other three
      execute fusion between the viral envelope and the plasma and endocytic membranes
      or the membranes of adjacent cells and are highly conserved among members of the
      herpesvirus family. Details of the interaction of gD with gB, gH, and gL were not
      known. Here, we report that the four glycoproteins assemble into a complex
      initiated by the interaction of gD with its cellular receptor. gB is recruited to
      the gD-receptor complex next, even in the absence of gH.gL. gH.gL is recruited
      next, but only to the receptor-gD-gB ensemble. A complex with the composition
      receptor-gD-gB-gH.gL is assembled transiently with a life span of 15-30 min in
      cells exposed to virus but can also be found in infected cells and in cells
      committed to form polykaryocytes after transfection of the glycoprotein quartet.
      The results indicate that the complex assembly is a critical step in the process
      of virus entry and fusion, and that no viral protein other than those that
      participate in the complex itself is required for complex assembly. These
      findings imply critical protein-protein interactions among the quartet as herpes
      simplex virions enter the cells and at cell-cell fusion, define a specific order
      of recruitment, and place gH.gL as the last link in the process of glycoprotein
      recruitment to the complex.

PMID- 16973745
TI  - Genome reduction in Leptospira borgpetersenii reflects limited transmission
      potential.
AB  - Leptospirosis is one of the most common zoonotic diseases in the world, resulting
      in high morbidity and mortality in humans and affecting global livestock
      production. Most infections are caused by either Leptospira borgpetersenii or
      Leptospira interrogans, bacteria that vary in their distribution in nature and
      rely on different modes of transmission. We report the complete genomic sequences
      of two strains of L. borgpetersenii serovar Hardjo that have distinct phenotypes
      and virulence. These two strains have nearly identical genetic content, with
      subtle frameshift and point mutations being a common form of genetic variation.
      Starkly limited regions of synteny are shared between the large chromosomes of L.
      borgpetersenii and L. interrogans, probably the result of frequent recombination
      events between insertion sequences. The L. borgpetersenii genome is approximately
      700 kb smaller and has a lower coding density than L. interrogans, indicating it
      is decaying through a process of insertion sequence-mediated genome reduction.
      Loss of gene function is not random but is centered on impairment of
      environmental sensing and metabolite transport and utilization. These features
      distinguish L. borgpetersenii from L. interrogans, a species with minimal genetic
      decay and that survives extended passage in aquatic environments encountering a
      mammalian host. We conclude that L. borgpetersenii is evolving toward dependence
      on a strict host-to-host transmission cycle.

PMID- 16973746
TI  - The molecular basis for T-type Ca2+ channel inhibition by G protein beta2gamma2
      subunits.
AB  - Gbetagamma, a ubiquitous second messenger, relays external signals from G protein
      coupled receptors to networks of intracellular effectors, including voltage
      dependent calcium channels. Unlike high-voltage-activated Ca(2+) channels, the
      inhibition of low-voltage-activated Ca(2+) channels is subtype-dependent and
      mediated selectively by Gbeta(2)-containing dimers. Yet, the molecular basis for
      this exquisite selectivity remains unknown. Here, we used pure recombinant
      Gbetagamma subunits to establish that the Gbeta(2)gamma(2) dimer can selectively
      reconstitute the inhibition of alpha(1H) channels in isolated membrane patches.
      This inhibition is the result of a reduction in channel open probability that is
      not accompanied by a change in channel expression or an alteration in active
      channel gating. By exchanging residues between the active Gbeta(2) subunit and
      the inactive Gbeta(1) subunit, we identified a cluster of amino acids that
      functionally distinguish Gbeta(2) from other Gbeta subunits. These amino acids on
      the beta-torus identify a region that is distinct from those regions that contact
      the Galpha subunit or other effectors.

PMID- 16973747
TI  - First-principles, quantum-mechanical simulations of electron solvation by a water
      cluster.
AB  - Despite numerous experiments and static electronic structure calculations, the
      nature of hydrated-electron clusters, (H2O)(n)(-), remains poorly understood.
      Here, we introduce a hybrid ab initio molecular dynamics scheme, balancing
      accuracy against feasibility, to simulate vibrational and photoelectron spectra
      of (H(2)O)(n)(-), treating all electrons quantum-mechanically. This methodology
      provides a computational tool for understanding the spectra of weakly bound and
      supramolecular anions and for elucidating the fingerprint of dynamics in these
      spectra. Simulations of (H2O)(4)(-) provide quantitative agreement with
      experimental spectra and furnish direct evidence of the nonequilibrium nature of
      the cluster ensemble that is probed experimentally. The simulations also provide
      an estimate of the cluster temperature (T approximately 150-200 K) that is not
      available from experiment alone. The "double acceptor" electron-binding motif is
      found to be highly stable with respect to thermal fluctuations, even at T = 300
      K, whereas the extra electron stabilizes what would otherwise be unfavorable
      water configurations.

PMID- 16973748
TI  - Quantitative phase tomography of Arabidopsis seeds reveals intercellular void
      network.
AB  - We used quantitative phase tomography with synchrotron radiation to elucidate the
      3D structure of Arabidopsis seeds in their native state. The cells are clearly
      distinguished, and their internal structure is revealed through local variations
      in electron density. We visualized a 3D network of intercellular air space that
      might allow immediate gas exchange for energy supply during germination and/or
      serve for rapid water uptake and distribution during imbibition.

PMID- 16973749
TI  - A rationally designed agonist antibody fragment that functionally mimics
      thrombopoietin.
AB  - By using rational design, antibody fragments (Fabs) that mimic thrombopoietin
      (TPO) were created. A peptide with cMpl receptor-binding capability was grafted
      into different complementarity-determining regions of a fully human Fab scaffold.
      Functional presentation of the peptide was optimized by using phage display and
      cell-based panning. Select antibodies and fragments containing two grafted
      peptides were assayed for their ability to stimulate the cMpl receptor in vitro.
      Several candidates demonstrated agonist activity in an in vitro cMpl receptor
      signaling reporter assay, including Fab59, which was estimated to be equipotent
      to TPO. Fab59 additionally was able to effectively stimulate platelet production
      in normal mice. These rationally designed mimetic Fabs may provide a therapeutic
      intervention for thrombocytopenia while avoiding the potential generation of
      neutralizing antibodies to endogenous TPO. Furthermore, this study demonstrates a
      method by which short-lived linear peptides with binding activity may be
      converted to more stable and potent agonists capable of activating cell surface
      receptors.

PMID- 16973750
TI  - Combinatorial activities of Akt and B-Raf/Erk signaling in a mouse model of
      androgen-independent prostate cancer.
AB  - Androgen independence is responsible for most prostate cancer lethality, yet
      currently there are no effective clinical treatments. We have been investigating
      the mechanisms underlying androgen-independent prostate cancer in Nkx3.1;Pten
      mutant mice, which display salient features of the disease, including a
      requirement for wild-type androgen receptor (AR) signaling. We now demonstrate
      that the Akt and Erk MAP kinase signaling pathways are activated in androgen
      independent lesions of these mice. Forced activation of either Akt or Erk
      signaling in an androgen-responsive prostate cancer cell line promotes hormone
      independent but AR-dependent growth in culture. Although these pathways act
      additively in culture, they act synergistically in vivo to promote tumorigenicity
      and androgen independence in the context of the prostate microenvironment. We
      propose that androgen independence emerges by means of epithelial-stromal
      competition, in which activation of Akt and Erk promotes AR activity in the
      prostate epithelium while counteracting antagonistic effects of the stroma.

PMID- 16973751
TI  - Prolactin/growth hormone-derived antiangiogenic peptides highlight a potential
      role of tilted peptides in angiogenesis.
AB  - Angiogenesis is a crucial step in many pathologies, including tumor growth and
      metastasis. Here, we show that tilted peptides exert antiangiogenic activity.
      Tilted (or oblique-oriented) peptides are short peptides known to destabilize
      membranes and lipid cores and characterized by an asymmetric distribution of
      hydrophobic residues along the axis when helical. We have previously shown that
      16-kDa fragments of the human prolactin/growth hormone (PRL/GH) family members
      are potent angiogenesis inhibitors. Here, we demonstrate that all these fragments
      possess a 14-aa sequence having the characteristics of a tilted peptide. The
      tilted peptides of human prolactin and human growth hormone induce endothelial
      cell apoptosis, inhibit endothelial cell proliferation, and inhibit capillary
      formation both in vitro and in vivo. These antiangiogenic effects are abolished
      when the peptides' hydrophobicity gradient is altered by mutation. We further
      demonstrate that the well known tilted peptides of simian immunodeficiency virus
      gp32 and Alzheimer's beta-amyloid peptide are also angiogenesis inhibitors. Taken
      together, these results point to a potential new role for tilted peptides in
      regulating angiogenesis.

PMID- 16973752
TI  - Rapid high-yield expression of full-size IgG antibodies in plants coinfected with
      noncompeting viral vectors.
AB  - Plant viral vectors allow expression of heterologous proteins at high yields, but
      so far, they have been unable to express heterooligomeric proteins efficiently.
      We describe here a rapid and indefinitely scalable process for high-level
      expression of functional full-size mAbs of the IgG class in plants. The process
      relies on synchronous coinfection and coreplication of two viral vectors, each
      expressing a separate antibody chain. The two vectors are derived from two
      different plant viruses that were found to be noncompeting. Unlike vectors
      derived from the same virus, noncompeting vectors effectively coexpress the heavy
      and light chains in the same cell throughout the plant body, resulting in yields
      of up to 0.5 g of assembled mAbs per kg of fresh-leaf biomass. This technology
      allows production of gram quantities of mAbs for research purposes in just
      several days, and the same protocol can be used on an industrial scale in
      situations requiring rapid response, such as pandemic or terrorism events.

PMID- 16973753
TI  - Deletion of microsomal prostaglandin E synthase-1 augments prostacyclin and
      retards atherogenesis.
AB  - Prostaglandin (PG) E(2) is formed from PGH(2) by a series of PGE synthase (PGES)
      enzymes. Microsomal PGES-1(-/-) (mPGES-1(-/-)) mice were crossed into low-density
      lipoprotein receptor knockout (LDLR(-/-)) mice to generate mPGES-1(-/-) LDLR(-/
      )s. Urinary 11alpha-hydroxy-9, 15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid
      (PGE-M) was depressed by mPGES-1 deletion. Vascular mPGES-1 was augmented during
      atherogenesis in LDLR(-/-)s. Deletion of mPGES-1 reduced plaque burden in fat-fed
      LDLR(-/-)s but did not alter blood pressure. mPGES-1(-/-) LDLR(-/-) plaques were
      enriched with fibrillar collagens relative to LDLR(-/-), which also contained
      small and intermediate-sized collagens. Macrophage foam cells were depleted in
      mPGES-1(-/-) LDLR(-/-) lesions, whereas the total areas rich in vascular smooth
      muscle cell (VSMC) and matrix were unaltered. mPGES-1 deletion augmented
      expression of both prostacyclin (PGI(2)) and thromboxane (Tx) synthases in
      endothelial cells, and VSMCs expressing PGI synthase were enriched in mPGES-1(-/
      ) LDLR(-/-) lesions. Stimulation of mPGES-1(-/-) VSMC and macrophages with
      bacterial LPS increased PGI(2) and thromboxane A(2) to varied extents. Urinary
      PGE-M was depressed, whereas urinary 2,3-dinor 6-keto PGF(1alpha), but not 2,3
      dinor-TxB(2), was increased in mPGES-1(-/-) LDLR(-/-)s. mPGES-1-derived PGE(2)
      accelerates atherogenesis in LDLR(-/-) mice. Disruption of this enzyme retards
      atherogenesis, without an attendant impact on blood pressure. This may reflect,
      in part, rediversion of accumulated PGH(2) to augment formation of PGI(2).
      Inhibitors of mPGES-1 may be less likely than those selective for cyclooxygenase
      2 to result in cardiovascular complications because of a divergent impact on the
      biosynthesis of PGI(2).

PMID- 16973754
TI  - Diversity of zebrafish peripheral oscillators revealed by luciferase reporting.
AB  - In various multicellular organisms, circadian clocks are present not only in the
      central nervous system, but also in peripheral organs and tissues. In mammals
      peripheral oscillators are not directly responsive to light, but are entrained by
      the central oscillator in the suprachiasmatic nucleus. These individual
      oscillators are diverse in their free-running periods and phases. In contrast,
      cultured peripheral tissues and cell lines from zebrafish are not only rhythmic,
      but can also be directly entrained by light. Because of the convenience of
      studying rhythms in cultured cells, however, little has been known about
      properties of individual oscillators in intact zebrafish. Here, we show the
      remarkable diversity and consistency of oscillator properties in various
      peripheral organs and tissues from the period3-luciferase (per3-luc) transgenic
      zebrafish. Tissue-dependent differences were found in free-running period, phase,
      response to light, and temperature compensation. Furthermore, cycling amplitudes
      were reduced at lower temperatures in some, but not all, of the organs tested.
      Finally, we found that per3-luc rhythms can free run in both constant dark and
      constant light with remarkably similar amplitudes, phases, and periods, despite
      the fact that the mRNA of per2 and per1 has been shown not to oscillate in
      constant light.

PMID- 16973755
TI  - StAR search--what we know about how the steroidogenic acute regulatory protein
      mediates mitochondrial cholesterol import.
AB  - Cholesterol is the starting point for biosynthesis of steroids, oxysterols and
      bile acids, and is also an essential component of cellular membranes. The
      mechanisms directing the intracellular trafficking of this insoluble molecule
      have received attention through the discovery of the steroidogenic acute
      regulatory protein (StAR) and related proteins containing StAR-related lipid
      transfer domains. Much of our understanding of the physiology of StAR derives
      from studies of congenital lipoid adrenal hyperplasia, which is caused by StAR
      mutations. Multiple lines of evidence show that StAR moves cholesterol from the
      outer to inner mitochondrial membrane, but acts exclusively on the outer
      membrane. The precise mechanism by which StAR's action on the outer mitochondrial
      membrane stimulates the flow of cholesterol to the inner membrane remains
      unclear. When StAR interacts with protonated phospholipid head groups on the
      outer mitochondrial membrane, it undergoes a conformational change (molten
      globule transition) that opens and closes StAR's cholesterol-binding pocket; this
      conformational change is required for cholesterol binding, which is required for
      StAR activity. The action of StAR probably requires interaction with the
      peripheral benzodiazepine receptor.

PMID- 16973756
TI  - Activation of pregnane X receptor disrupts glucocorticoid and mineralocorticoid
      homeostasis.
AB  - The pregnane X receptor (PXR) was isolated as a xenobiotic receptor that
      regulates responses to various xenobiotic agents. In this study, we show that PXR
      plays an important endobiotic role in adrenal steroid homeostasis. Activation of
      PXR by genetic (transgene) or pharmacological (ligand, such as rifampicin)
      markedly increased plasma concentrations of corticosterone and aldosterone, the
      respective primary glucocorticoid and mineralocorticoid in rodents. The increased
      levels of corticosterone and aldosterone were associated with activation of
      adrenal steroidogenic enzymes, including cytochrome P450 (CYP)11a1, CYP11b1,
      CYP11b2, and 3beta-hydroxysteroid dehydrogenase. The PXR-activating transgenic
      mice also exhibited hypertrophy of the adrenal cortex, loss of glucocorticoid
      circadian rhythm, and lack of glucocorticoid responses to psychogenic stress.
      Interestingly, the transgenic mice had normal pituitary secretion of ACTH and the
      corticosterone-suppressing effect of dexamethasone was intact, suggesting a
      functional hypothalamus-pituitary-adrenal axis despite a severe disruption of
      adrenal steroid homeostasis. The ACTH-independent hypercortisolism in the PXR
      activating transgenic mice is reminiscent of the pseudo-Cushing's syndrome in
      patients. The glucocorticoid effect appears to be PXR specific, as the activation
      of constitutive androstane receptor in transgenic mice had little effect. We
      propose that PXR is a potential endocrine disrupting factor that may have broad
      implications in steroid homeostasis and drug-hormone interactions.

PMID- 16973757
TI  - The expression profiles of nuclear receptors in the developing and adult kidney.
AB  - Nuclear receptors are transcriptional regulators that play important roles in
      embryonic development and organogenesis. To study the potential roles of nuclear
      receptors in kidney development, we examined the expression patterns of a subset
      of nuclear receptors in which specific antibodies are available for profiling
      using immunohistochemistry. As a prototype for our analysis, we investigated the
      expression patterns of chicken ovalbumin upstream promoter transcription factor
      (COUP-TF) -I and -II in more details during embryonic development and in the
      adult by immunohistochemistry. We showed that COUP-TFI is expressed in the stroma
      and mesenchymal cells at embryonic d 11.5 (E11.5) and expression persists
      throughout embryonic development. In the adult kidney, only mesangial cells show
      meaningful COUP-TFI expression. In contrast, COUP-TFII expression is detected as
      early as E9.5 and high expression is seen in the mesenchymal-derived epithelial
      cells but not in the ureteric buds through E12.5. At E13.5, COUP-TFII expression
      becomes regionalized with higher expression in the region that gives rise to the
      distal tubule. The proximal part of the S-shaped body that will become the
      glomerulus after endothelial cell migration shows COUP-TFII expression in
      podocyte precursor cells and epithelial cells of the Bowman's capsule. In the
      adult mouse kidney, COUP-TFII is detected in distal tubules, podocytes, and the
      epithelial cells of the Bowman's capsule. In addition to COUP-TFs, we also
      examined the expression profiles of eight other nuclear receptors (farnesoid X
      receptor, vitamin D receptor, hepatocyte nuclear factor 4alpha, retinoid X
      receptor alpha, mineralocorticoid receptor, steroidogenic factor 1, liver
      receptor homolog-1, and germ cell nuclear factor). Our results suggest that these
      nuclear receptors are likely to play important physiological roles in the kidney
      development.

PMID- 16973758
TI  - Progesterone receptor repression of prolactin/signal transducer and activator of
      transcription 5-mediated transcription of the beta-casein gene in mammary
      epithelial cells.
AB  - Prolactin (PRL) and glucocorticoids act synergistically to stimulate
      transcription of the beta-casein milk protein gene. Signal transducer and
      activator of transcription 5 (Stat5) mediates PRL-dependent trans-activation, and
      glucocorticoid potentiation occurs through cross talk between glucocorticoid
      receptor (GR) and Stat5 at the beta-casein promoter. In the mouse, progesterone
      withdrawal leads to terminal differentiation and secretory activation of the
      mammary gland at parturition, indicating progesterone's role in repressing milk
      protein gene expression during pregnancy. To investigate the mechanism of the
      inhibitory action of progesterone, experiments were performed with cell culture
      systems reconstituted to express progesterone receptor (PR), the PRL
      receptor/Stat5 signaling pathway, and GR, enabling evaluation of PR, GR, and
      Stat5 interactions at the beta-casein promoter. With COS-1, normal murine mammary
      gland, HC-11, and primary mammary epithelial cells, progestin-PR directly
      repressed the PRL receptor/Stat5a signaling pathway's mediation of PRL-induced
      beta-casein transcription. Progestin-PR also inhibited glucocorticoid-GR
      enhancement of PRL induced trans-activation of beta-casein. Inhibition depended
      on a functional PR DNA binding domain and specific PR-DNA interactions at the
      beta-casein promoter. Chromatin immunoprecipitation assays in HC-11 cells
      revealed recruitment of PR and Stat5a to the beta-casein promoter by progestin or
      PRL, respectively. Recruitment was disrupted by cotreatment with progestin and
      PRL, suggesting a mutual interference between activated PR and Stat5a. Without
      PRL, progestin-PR also recruited Stat5a to the beta-casein promoter, suggesting
      that recruitment of an unactivated form of Stat5a may contribute to inhibition of
      beta-casein by progesterone. These results define a negative cross talk between
      PR and Stat5a/GR that may contribute to the physiological role of progesterone to
      repress lactogenic hormone induction of the beta-casein gene in the mammary gland
      during pregnancy.

PMID- 16973760
TI  - Liver X receptors regulate adrenal steroidogenesis and hypothalamic-pituitary
      adrenal feedback.
AB  - The nuclear hormone receptors liver X receptor alpha (LXRalpha) (NR1H3) and
      LXRbeta (NR1H2) are established regulators of cholesterol, lipid, and glucose
      metabolism and are attractive drug targets for the treatment of diabetes and
      cardiovascular disease. Adrenal steroid hormones including glucocorticoids and
      mineralocorticoids are known to interfere with glucose metabolism, insulin
      signaling, and blood pressure regulation. Here we present genome-wide expression
      profiles of LXR-responsive genes in both the adrenal and the pituitary gland. LXR
      activation in cultured adrenal cells inhibited expression of multiple
      steroidogenic genes and consequently decreased adrenal steroid hormone
      production. In addition, LXR agonist treatment elevated ACTH mRNA expression and
      hormone secretion from pituitary cells both in vitro and in vivo. Reduced
      expression of the glucocortioid-activating enzyme 11beta-hydroxysteroid
      dehydrogenase 1 in pituitary cells upon LXR activation suggests blunting of the
      negative feedback of glucocorticoids by LXRs. In conclusion, LXRs independently
      interfere with the hypothalamic-pituitary-adrenal axis regulation at the level of
      the pituitary and the adrenal gland.

PMID- 16973759
TI  - A delayed gonadotropin-dependent and growth factor-mediated activation of the
      extracellular signal-regulated kinase 1/2 cascade negatively regulates aromatase
      expression in granulosa cells.
AB  - Human chorionic gonadotropin and human FSH (hFSH) elicit a transient increase in
      ERK1/2 phosphorylation lasting less than 60 min in immature granulosa cells
      expressing a low density of gonadotropin receptors. In cells expressing a high
      density of receptors, human chorionic gonadotropin and human FSH elicit this fast
      transient increase in ERK1/2 phosphorylation and also a delayed and more
      sustained increase that is detectable after 6-9 h. Both the early and delayed
      increases in ERK1/2 phosphorylation can be blocked with inhibitors of protein
      kinase A, the epidermal growth factor receptor kinase, metalloproteases, and MAPK
      kinase. The delayed effect, but not the early effect, can also be blocked with an
      inhibitor of protein kinase C. Because the delayed increase in ERK1/2
      phosphorylation correlates with low aromatase expression in response to
      gonadotropins, we tested the effects of these inhibitors on aromatase expression.
      These inhibitors had little or no effect on gonadotropin-induced aromatase
      expression in cells expressing a low density of receptors, but they enhanced
      gonadotropin-induced aromatase expression in cells expressing a high density of
      receptors. Phorbol esters also induced a prolonged increase in ERK1/2
      phosphorylation and, when added together with hFSH, blocked the induction of
      aromatase expression by hFSH in cells expressing a low density of hFSH receptor.
      A MAPK kinase inhibitor reversed the inhibitory effect of the phorbol ester on
      aromatase induction. We conclude that the effects of gonadotropins on ERK1/2
      phosphorylation are mediated by epidermal growth factor-like growth factors and
      that the delayed effect is partially mediated by protein kinase C and acts as a
      negative regulator of aromatase expression.

PMID- 16973761
TI  - Conserved amino acid residues that are important for ligand binding in the type I
      gonadotropin-releasing hormone (GnRH) receptor are required for high potency of
      GnRH II at the type II GnRH receptor.
AB  - GnRH I regulates reproduction. A second form, designated GnRH II, selectively
      binds type II GnRH receptors. Amino acids of the type I GnRH receptor required
      for binding of GnRH I (Asp2.61(98), Asn2.65(102), and Lys3.32(121)) are conserved
      in the type II GnRH receptor, but their roles in receptor function are unknown.
      We have delineated their functions using mutagenesis, signaling and binding
      assays, immunoblotting, and computational modeling. Mutating Asp2.61(97) to Glu
      or Ala, Asn2.65(101) to Ala, or Lys3.32(120) to Gln decreased potency of GnRH II
      stimulated inositol phosphate production. Consistent with proposed roles in
      ligand recognition, mutations eliminated measurable binding of GnRH II, whereas
      expression of mutant receptors was not decreased. In detailed analysis of how
      these residues affect ligand-dependent signaling, [Trp2]-GnRH I showed lesser
      decreases in potency than GnRH I at the Asp2.61(97)Glu mutant. In contrast,
      [Trp2]-GnRH II showed the same loss of potency as GnRH II at this mutant. This
      suggests that Asp2.61(97) contributes to recognition of His2 of GnRH I, but not
      of GnRH II. GnRH II showed a large decrease in potency at the Asn2.65(101)Ala
      mutant compared with analogs lacking the CO group of Gly10NH2. This suggests that
      Asn2.65(101) recognizes Gly10NH2 of GnRH II. GnRH agonists showed large decreases
      in potency at the Lys3.32(120)Gln mutant, but antagonist activity was unaffected.
      This suggests that Lys3.32(120) recognizes agonists, but not antagonists, as in
      the type I receptor. These data indicate that roles of conserved residues are
      similar, but not identical, in the type I and II GnRH receptors.

PMID- 16973762
TI  - Recent increase of neighborhood socioeconomic effects on ischemic heart disease
      mortality: a multilevel survival analysis of two large Swedish cohorts.
AB  - Studies have shown that the decrease in ischemic heart disease mortality over the
      past decades was paralleled by an increase in socioeconomic disparities. Using
      two large Swedish cohorts defined in 1986 and 1996, the authors examined whether
      the effect of neighborhood socioeconomic position on ischemic heart disease
      mortality strengthened over the period and whether the relative contribution of
      individual and neighborhood socioeconomic effects changed over time. Multilevel
      survival models adjusted for individual factors indicated that neighborhood
      socioeconomic effects on ischemic heart disease mortality increased markedly
      between the two periods (hazard ratios for residing in the most vs. least
      deprived neighborhoods were 1.60 (95% credible interval: 1.36, 1.89) for the 1986
      cohort and 2.54 (95% credible interval: 1.99, 3.21) for the 1996 cohort).
      Comparing the neighborhood socioeconomic effect with the strongly predictive
      effect of 15-year individual income indicated that the neighborhood effect was
      two times weaker than the individual effect in the 1986 cohort (-48%, 95%
      credible interval: -22%, -68%) but of comparable magnitude in the 1996 cohort (
      11%, 95% credible interval: -42%, 29%). This increase in the contribution of
      neighborhood factors to the socioeconomic gradient in ischemic heart disease
      urges investigation into the exact mechanisms between the residential context and
      coronary health.

PMID- 16973765
TI  - Peripheral neuropathies of the median, radial, and ulnar nerves: MR imaging
      features.
AB  - The median, radial, and ulnar nerves of the upper limbs may be affected by
      various peripheral neuropathies, each of which may be categorized according to
      its cause, as either an entrapment or a nonentrapment neuropathy. Entrapment
      neuropathies, also referred to as nerve compression syndromes, include the
      supracondylar process syndrome, pronator syndrome, anterior interosseous nerve
      syndrome, carpal tunnel syndrome, posterior interosseous nerve syndrome, cubital
      tunnel syndrome, and Guyon canal syndrome. Nonentrapment neuropathies include
      traumatic nerve injuries, infectious and inflammatory conditions,
      polyneuropathies, and mass lesions at anatomic locations where entrapment
      syndromes typically do not occur. Although clinical examination and
      electrophysiologic testing are the cornerstone of the diagnostic work-up, in
      certain cases magnetic resonance (MR) imaging may provide key information about
      the exact anatomic location of a lesion or may help narrow the differential
      diagnosis. In patients with a diagnosis of peripheral neuropathy, MR imaging may
      help establish the cause of the condition and provide information crucial for
      conservative management or surgical planning. In addition, knowledge of the
      normal anatomy and of the possible causes, typical clinical findings, and MR
      imaging features of peripheral neuropathies that affect the median, radial, and
      ulnar nerves allows greater confidence in the diagnosis.

PMID- 16973766
TI  - Superficial soft-tissue masses of the extremities.
AB  - Superficial soft-tissue masses are among the most common indications for imaging
      of the extremities. A broad array of benign and malignant processes may be
      manifested in palpable cutaneous or subcutaneous masses or nodules. Most such
      lesions are treated with surgical excision, but some may be conservatively
      managed. The lesions can be differentiated according to their location in one or
      more skin layers (epidermis, dermis, and subcutis), their histologic composition,
      and the associated anatomic abnormality or disease process. Because the imaging
      characteristics of many benign soft-tissue lesions overlap with those of
      malignant ones, knowledge of the patient's clinical history (including any
      laboratory test results) and direct visual examination of the lesion often are
      important for differentiation. Histologic analysis may be necessary to achieve a
      definitive diagnosis.

PMID- 16973767
TI  - VIRTOPSY: minimally invasive, imaging-guided virtual autopsy.
AB  - Invasive "body-opening" autopsy represents the traditional means of postmortem
      investigation in humans. However, modern cross-sectional imaging techniques can
      supplement and may even partially replace traditional autopsy. Computed
      tomography (CT) is the imaging modality of choice for two- and three-dimensional
      documentation and analysis of autopsy findings including fracture systems,
      pathologic gas collections (eg, air embolism, subcutaneous emphysema after
      trauma, hyperbaric trauma, decomposition effects), and gross tissue injury.
      Various postprocessing techniques can provide strong forensic evidence for use in
      legal proceedings. Magnetic resonance (MR) imaging has had a greater impact in
      demonstrating soft-tissue injury, organ trauma, and nontraumatic conditions.
      However, the differences in morphologic features and signal intensity
      characteristics seen at antemortem versus postmortem MR imaging have not yet been
      studied systematically. The documentation and analysis of postmortem findings
      with CT and MR imaging and postprocessing techniques ("virtopsy") is investigator
      independent, objective, and noninvasive and will lead to qualitative improvements
      in forensic pathologic investigation. Future applications of this approach
      include the assessment of morbidity and mortality in the general population and,
      perhaps, routine screening of bodies prior to burial.

PMID- 16973768
TI  - Pearls and pitfalls in interpretation of abdominal and pelvic PET-CT.
AB  - The interpretation of images obtained in the abdomen and pelvis can be
      challenging, and the coregistration of positron emission tomographic (PET) and
      computed tomographic (CT) scans may be especially valuable in the evaluation of
      these anatomic areas. PET-CT represents a major technologic advance, consisting
      of generally complementary modalities whose combined strength tends to overcome
      their respective weaknesses. However, this combined functional-structural imaging
      approach raises a number of controversial questions and presents some unique
      interpretative challenges. Accurate PET-CT scan interpretation requires awareness
      of the various pitfalls associated with the imaging components, both individually
      and in combination. The results of recent PET-CT studies have been very
      encouraging, but larger prospective studies will be needed to establish optimal
      hybrid scanning protocols. Applying sound imaging principles, paying attention to
      detail, and staying abreast of advances in this exciting new modality are
      necessary for harnessing the full diagnostic power of abdominopelvic PET-CT.

PMID- 16973769
TI  - Radiology of the laparoscopic Roux-en-Y gastric bypass procedure:
      conceptualization and precise interpretation of results.
AB  - Obesity is an epidemic in the United States. The laparoscopic Roux-en-Y gastric
      bypass procedure is an effective surgical intervention that can produce dramatic
      weight loss in morbidly obese patients. Despite the inherent risks, the surgery
      is increasing in popularity. Radiology plays a crucial role in postoperative
      evaluation. Upper gastrointestinal (UGI) series and abdominal computed tomography
      (CT) are the primary radiologic tools used in assessment of possible
      complications. With knowledge of the normal postoperative appearance, performance
      of UGI studies and interpretation of the results should be easy. The 24-hour
      postoperative examination allows reliable detection of anastomotic leaks.
      Although strictures of the gastrojejunal anastomosis are a common complication,
      they are often diagnosed and treated with endoscopy. In a thorough examination,
      one also evaluates for degraded pouch restriction, including a patulous
      gastrojejunal anastomosis or gastrogastric fistula, as a late cause of weight
      gain. Knowledge of the postoperative anatomy also assists in detection of
      internal hernias. CT is invaluable in detection and characterization of small
      bowel obstructions and internal hernias. CT may allow diagnosis of anastomotic
      leaks, abscesses, gastrogastric fistulas, and intra-abdominal hematomas. CT
      guided percutaneous procedures, such as placement of gastrostomy tubes or
      drainage of fluid collections, can obviate emergency exploration and may be the
      only procedural intervention necessary for a cure.

PMID- 16973770
TI  - Multi-detector row CT: spectrum of diseases involving the ileocecal area.
AB  - The ileocecal area is a relatively short segment of the gastrointestinal tract
      but may be affected by pathologic conditions that are either common throughout
      the gastrointestinal system or exclusive to this area. These conditions include
      benign and malignant tumors, inflammatory processes (appendicitis,
      diverticulitis, epiploic appendagitis, Crohn disease), infectious diseases, and
      miscellaneous conditions (cecal ischemia, typhlitis, cecal volvulus, duplication
      cyst). The various components of the ileocecal area (cecum, appendix, ileocecal
      valve, terminal ileum) are close to one another, so that these conditions may
      involve more than one anatomic structure, thereby creating a diagnostic dilemma.
      The evaluation of various parameters (eg, stratified enhancement pattern of the
      thickened bowel wall, degree of thickening, extent and location of bowel wall
      involvement, degree of fat stranding relative to the degree of wall thickening)
      and associated findings (lymph nodes, mesenteric stranding, abscess and sinus
      tracts, fatty proliferation, solid organ abnormalities) will help narrow the
      differential diagnosis. Multi-detector row computed tomography (CT) is considered
      the best imaging examination for the evaluation of the ileocecal area.
      Consequently, the radiologist should be familiar with the multi-detector row CT
      features of the spectrum of diseases affecting this area to help ensure correct
      diagnosis and appropriate treatment.

PMID- 16973771
TI  - Anatomic and pathologic findings at external phased-array pelvic MR imaging after
      surgery for anorectal disease.
AB  - Pelvic magnetic resonance (MR) imaging is useful for identification of
      postoperative changes, complications, and disease recurrence in patients who have
      undergone surgery for primary or recurrent anorectal disease. Commonly used
      interventions include treatment for anorectal carcinoma: anterior rectal
      resection with or without creation of different colic anastomoses and
      abdominoperineal excision with or without pelvic reconstruction (omentoplasty,
      placement of myocutaneous flaps). Other common interventions include treatment
      for inflammatory bowel disease (coloproctectomy with or without creation of an
      ileoanal anastomosis and ileal pouch) and treatment for fistulas (placement of
      flaps or setons). Postoperative anatomic changes and formation of scar tissue can
      usually be identified with consecutive MR imaging examinations. Pelvic MR imaging
      is an accurate technique for assessment of complications including anastomotic
      leakage, septic complications such as fistulas and abscesses, neoplastic
      recurrence, and other less common complications (perineal hernia, peritoneal
      pseudocyst). The sophisticated surgical procedures used in rectal surgery can
      alter normal anatomy and make image interpretation difficult. Thus, familiarity
      with the appearances of postoperative anatomic changes, complications, and tumor
      recurrence is essential for accurate MR imaging evaluation after surgery for
      anorectal disease.

PMID- 16973772
TI  - Dual gradient-echo in-phase and opposed-phase hepatic MR imaging: a useful tool
      for evaluating more than fatty infiltration or fatty sparing.
AB  - A T1-weighted gradient-echo in-phase and opposed-phase sequence has become a
      routine part of every hepatic magnetic resonance (MR) imaging protocol. Although
      this sequence is primarily used to identify common pathologic conditions, such as
      diffuse or focal steatosis and focal fatty sparing, it is also helpful in
      detection of pathologic entities associated with T2* effects owing to the double
      echo approach. Thus, pathologic conditions such as hemochromatosis or
      hemosiderosis can be identified and characterized with a high level of
      confidence. In cases of iron storage disease, the hepatic parenchymal signal
      intensity decreases on the image with the longer echo time due to the continued
      decay of the transverse magnetization. In addition, susceptibility artifacts can
      be easily detected and characterized with in-phase and opposed-phase MR imaging.
      Metallic objects demonstrate a larger susceptibility artifact on the image with
      the second or longer echo time, which is usually the in-phase image. Finally,
      intrahepatic pneumobilia can be identified with the T1-weighted gradient-echo in
      phase and opposed-phase sequence because gas also causes a susceptibility
      artifact, which is more pronounced on the image with the longer echo time. A
      complete understanding of both the chemical shift cancellation artifact and the
      T2* effects of the in-phase and opposed-phase sequence is important for correct
      interpretation of hepatic MR images.

PMID- 16973773
TI  - CT and MR imaging of complications of partial nephrectomy.
AB  - The standard treatment for renal cell carcinoma for many years was radical
      nephrectomy, but in the past decade there has been a trend toward elective
      nephron-sparing surgery. Initially, partial nephrectomy was performed with an
      open surgical approach; more recently and with increasing frequency, a
      laparoscopic approach has been used in selected cases. Nephron-sparing surgery
      with either approach is more complex than is traditional radical nephrectomy and
      more frequently results in complications. The possible complications of partial
      nephrectomy include vascular, collecting system, and technical complications as
      well as recurrent tumor and infection. For prompt diagnosis and appropriate
      management of these complications, radiologists must be familiar with normal and
      abnormal features in the postoperative appearance of the kidney at computed
      tomography and magnetic resonance imaging.

PMID- 16973774
TI  - Developing an MR imaging strategy for diagnosis of ovarian masses.
AB  - Magnetic resonance (MR) imaging provides useful information for characterization
      of various ovarian masses as neoplastic or nonneoplastic and, when neoplastic, on
      a spectrum from benign to malignant. The use of MR imaging for diagnosis of
      ovarian masses includes consideration of morphologic characteristics and signal
      intensity characteristics on T1- and T2-weighted images. The morphologic
      characteristics of cystic masses, cystic and solid masses, and predominantly
      solid masses provide important information. In general, cystic masses represent
      benign tumors, whereas cystic and solid masses are strongly associated with
      malignancy. Predominantly solid masses include benign, borderline malignant, and
      malignant tumors. T1-weighted images provide useful information for
      characterization because hemorrhagic adnexal masses (eg, endometriotic cyst) and
      cystic teratomas can be correctly diagnosed when the mass has high signal
      intensity. Significant low signal intensity in solid masses on T2-weighted images
      is indicative of fibrothecomas and Brenner tumors because extensive fibrous
      tissue produces significant low signal intensity on T2-weighted images. A
      strategy for diagnosis of ovarian masses with MR imaging incorporates signal
      intensity characteristics into morphologic characteristics.

PMID- 16973775
TI  - Radiographic and CT findings of thoracic complications after pneumonectomy.
AB  - Pneumonectomy is the treatment of choice for bronchogenic carcinoma and
      intractable end-stage lung diseases such as tuberculosis and bronchiectasis, but
      it is often followed by postoperative complications, which account for
      significant morbidity and mortality. Knowledge of the radiologic features of such
      complications is of critical importance for their early detection and prompt
      management. Complications of pneumonectomy are classified as early or late,
      depending on when they occur in relation to the hospitalization period. Early
      complications of pneumonectomy include pulmonary edema, bronchopleural fistula,
      pneumonia of the contralateral lung, empyema, and adult respiratory distress
      syndrome, which may occur separately or in combination. Late postpneumonectomy
      complications include recurrent disease, infection, effects of radiation therapy
      or chemotherapy, and surgical complications such as late-onset bronchopleural
      fistula, postpneumonectomy syndrome, and esophagopleural fistula. Sequential
      examinations with chest radiography after pneumonectomy are an invaluable method
      of screening for these complications, especially in the early postoperative
      period. When the radiographic findings are inconclusive, computed tomography is
      helpful for establishing a diagnosis and obtaining detailed information about the
      disease process.

PMID- 16973776
TI  - How to optimize clinical breast MR imaging practices and techniques on Your 1.5-T
      system.
AB  - Magnetic resonance (MR) imaging, when used in conjunction with mammography and
      ultrasonography, can be a powerful tool for breast imaging. There are various
      clinical scenarios in which MR imaging may provide key information that leads to
      an alteration in treatment plans (eg, by demonstrating features that were occult
      at physical examination or conventional imaging). Although many benign and
      malignant entities enhance at contrast material-enhanced breast MR imaging, the
      morphologic characteristics and kinetic profiles of lesions help narrow the
      differential diagnosis. To optimize the quality of the morphologic and kinetic
      information yielded by breast MR imaging, the radiologist must attend to various
      practical and technical prerequisites: A bilateral breast coil should be used
      with prone positioning of the patient. An MR imaging system with a high-field
      strength magnet is needed, and the magnetic field must be homogeneous across the
      field of view, which should include both breasts. A T2-weighted sequence should
      be applied first to identify any cysts and should be followed by three
      dimensional imaging with a T1-weighted spoiled gradient-echo sequence after the
      intravenous administration of a gadolinium chelate. To minimize artifacts, a
      direction other than the anterior-posterior direction should be selected for
      phase encoding. To suppress the signal from fat, a frequency-selective pulse
      should be applied during imaging, or the unenhanced MR imaging data should be
      subtracted from the contrast-enhanced MR imaging data during postprocessing. The
      imaging section thickness should be 3 mm or less, the pixel size should be less
      than 1 mm in each in-plane direction, and the total acquisition time should be
      less than 2 minutes.

PMID- 16973777
TI  - Intestinal malrotation in children: a problem-solving approach to the upper
      gastrointestinal series.
AB  - Intestinal malrotation, which is defined by a congenital abnormal position of the
      duodenojejunal junction, may lead to midgut volvulus, a potentially life
      threatening complication. An evaluation for malrotation is part of every upper
      gastrointestinal (GI) tract examination in pediatric patients, particularly
      neonates and infants. Although the diagnosis of malrotation is often
      straightforward, the imaging features in approximately 15% of upper GI tract
      examinations are equivocal and lead to a false-positive or false-negative
      interpretation. The clinical manifestations and upper GI tract findings of
      malrotation in older children and adults are less specific than are those in
      younger patients, and for this reason diagnosis of the condition may be more
      difficult. Successful differentiation between a normal variant and malrotation
      requires the use of optimal techniques in acquiring and interpreting the upper GI
      series. Familiarity with the upper GI series appearance of both normal and
      abnormal anatomic variants allows the radiologist to increase both diagnostic
      accuracy and confidence in the diagnosis of malrotation.

PMID- 16973778
TI  - It's not a cervical lymph node, it's a vein: CT and MR imaging findings in the
      veins of the head and neck.
AB  - The anatomy and imaging appearances of the veins of the head and neck can vary
      considerably, and normal veins may mimic disease processes at computed tomography
      (CT) and magnetic resonance (MR) imaging. On unenhanced CT scans, aberrant veins
      may be difficult to differentiate from lymph nodes or other pathologic
      conditions. Even at contrast material-enhanced CT, differences in venous
      enhancement or the mixing of opacified with nonopacified blood can lead to
      confusion, particularly if the vein is focally dilated. Similarly, the size and
      signal intensity of head and neck veins may vary at MR imaging due to slow or
      turbulent flow or variable enhancement, resulting in misdiagnosis. A thorough
      understanding of the normal venous anatomy and common variants is necessary to
      properly differentiate an unopacified or focally dilated vein from
      lymphadenopathy or some other disease entity and can help the radiologist avoid
      the erroneous interpretation of findings.

PMID- 16973779
TI  - Cerebral amyloid angiopathy: CT and MR imaging findings.
AB  - Cerebral amyloid angiopathy (CAA) is an important but underrecognized cause of
      cerebrovascular disorders that predominantly affect elderly patients. CAA results
      from deposition of beta-amyloid protein in cortical, subcortical, and
      leptomeningeal vessels. This deposition is responsible for the wide spectrum of
      clinical symptoms and neuroimaging findings. Many cases of CAA are asymptomatic.
      However, when cases are symptomatic, patients can present with transient
      neurologic events, progressive cognitive decline, or potentially devastating
      intracranial hemorrhage. Computed tomography is the imaging study of choice for
      evaluation of suspected acute cortical hemorrhage, which may be accompanied by
      subarachnoid, subdural, or intraventricular hemorrhage. Magnetic resonance
      imaging is best suited for identification of small or chronic cortical
      hemorrhages and ischemic sequelae of this disease, exclusion of other causes of
      acute cortical-subcortical hemorrhage, and assessment of disease progression.
      Accurate recognition of imaging findings is important in guiding clinical
      decision making in patients with CAA.

PMID- 16973780
TI  - An investigation of operator exposure in interventional radiology.
AB  - A study was conducted to investigate how operator exposure in interventional
      radiology is affected by various common fluoroscopic imaging conditions. Stray
      radiation levels surrounding the imaging chain of a C-arm angiographic system
      were measured with an anthropomorphic abdomen phantom under different imaging
      conditions, and isodose curves were constructed. Operator exposure was shown to
      increase with patient dose-area product as the imaging field of view (FOV) is
      changed, with the highest scatter levels occurring with an intermediate-sized
      FOV. Use of copper spectral beam filtration was found to result in decreased
      operator exposure, whereas use of wedge-shaped equalization filters was found to
      increase exposure. The effect of increasing patient abdomen thickness was
      simulated by surrounding the phantom with plastic bolus material. Increasing the
      thickness by 5 cm resulted in a doubling of exposure at the operator's waist.
      Exposure to the operator's upper body was significantly reduced when the FOV was
      positioned on the far side of the patient. Operator exposure can be maintained at
      an acceptable level by taking these variables into consideration and
      incorporating the suggested dose reduction techniques into routine practice to
      the greatest extent possible.

PMID- 16973782
TI  - Best cases from the AFIP: Ascaris pancreatitis.

PMID- 16973781
TI  - From the archives of the AFIP: Imaging of synovial sarcoma with radiologic
      pathologic correlation.
AB  - Synovial sarcoma is the fourth most common type of soft-tissue sarcoma,
      accounting for 2.5%-10.5% of all primary soft-tissue malignancies worldwide.
      Synovial sarcoma most often affects the extremities (80%-95% of cases),
      particularly the knee in the popliteal fossa, of adolescents and young adults (15
      40 years of age). Despite its name, the lesion does not commonly arise in an
      intraarticular location but usually occurs near joints. Histologic subtypes
      include monophasic, biphasic, and poorly differentiated; the cytogenetic
      aberration of the t(X;18) translocation is highly specific for synovial sarcoma.
      Although radiographic features of these tumors are not pathognomonic, findings of
      a soft-tissue mass, particularly if calcified (30%), near but not in a joint of a
      young patient, are very suggestive of the diagnosis. Cross-sectional imaging
      features are vital for staging tumor extent and planning surgical resection; they
      also frequently reveal suggestive appearances of multilobulation and marked
      heterogeneity (creating the "triple sign") with hemorrhage, fluid levels, and
      septa (creating the "bowl of grapes" sign). Two features associated with synovial
      sarcoma that may lead to an initial mistaken diagnosis of a benign indolent
      process are slow growth (average time to diagnosis, 2-4 years) and small size (<
      5 cm at initial presentation); in addition, these lesions may demonstrate well
      defined margins and homogeneous appearance on cross-sectional images. Synovial
      sarcoma is an intermediate- to high-grade lesion, and, despite initial aggressive
      wide surgical resection, local recurrence and metastatic disease are common and
      prognosis is guarded. Understanding and recognizing the spectrum of appearances
      of synovial sarcoma, which reflect the underlying pathologic characteristics,
      improve radiologic assessment and are important for optimal patient management.

PMID- 16973784
TI  - Characterization of 37 breed-specific single-nucleotide polymorphisms in sheep.
AB  - We identified 37 single-nucleotide polymorphisms (SNPs) in sheep and screened 16
      individuals from 8 different sheep breeds selected throughout Europe. Population
      genetic measures based on the genotyping of about 30 sheep from the same 8 breeds
      are reported. To date, there are no sheep SNPs documented in the National Center
      for Biotechnology Information dbSNP database. Therefore, the markers presented
      here contribute significantly to those currently available.

PMID- 16973785
TI  - Peer-professional first-person account: schizophrenia from the inside-
      phenomenology and the integration of causes and meanings.
AB  - An autobiographical account of the author's psychotic crisis blends his own
      insights with relevant extant research on schizophrenia. As an investigator in
      the fields of paranoia and schizophrenia research, who has himself been
      psychotic, this may help to link the narratives of professionals and patients.
      The episode is interpreted as having been precipitated by abuse of a person with
      susceptibilities to psychosis in terms of his attentional style, poor context
      apprehension, high emotional intensity, and poor emotion and arousal modulation.
      The most effective therapies proved to be a blend of haloperidol medication,
      cognitive and psychodynamic insight, and a total change of social scenario to an
      ambience less abusive of feminine men (the author used to be a transvestite).
      Throughout the narrative presented, it is clear that qualities of experiential
      life were not merely causally impotent responses to brain processes but
      themselves inducing of critical decisions and of outlook on life that played a
      large part in the eventuation of, and recovery from, the psychotic state.

PMID- 16973786
TI  - Three-year follow-up of a randomized controlled trial of cognitive therapy for
      the prevention of psychosis in people at ultrahigh risk.
AB  - There have been recent advances in the ability to identify people at high risk of
      developing psychosis. This has led to interest in the possibility of preventing
      the development of psychosis. A randomized controlled trial compared cognitive
      therapy (CT) over 6 months with monthly monitoring in 58 patients meeting
      criteria for ultrahigh risk of developing a first episode of psychosis.
      Participants were followed up over a 3-year period. Logistic regression
      demonstrated that CT significantly reduced likelihood of being prescribed
      antipsychotic medication over a 3-year period, but it did not affect transition
      to psychosis defined using the Positive and Negative Syndrome Scale (PANSS) or
      probable Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
      diagnosis. However, exploratory analyses revealed that CT significantly reduced
      the likelihood of making progression to psychosis as defined on the PANSS over 3
      years after controlling for baseline cognitive factors. Follow-up rate at 3 years
      was 47%. There appear to be enduring benefits of CT over the long term,
      suggesting that it is an efficacious intervention for people at high risk of
      developing psychosis.

PMID- 16973787
TI  - Yet more evidence that osteoarthritis is not a cartilage disease.

PMID- 16973788
TI  - Osteoarthritis linkage scan: more loci for the geneticists to investigate.

PMID- 16973789
TI  - Association of polymorphisms in the peroxisome proliferator-activated receptor
      gamma gene and osteoarthritis of the knee.
AB  - OBJECTIVES: To study the association between two common polymorphisms in the
      peroxisome proliferator-activated receptor gamma (PPARgamma) gene and
      susceptibility to, and severity of, osteoarthritis in a French-Canadian
      population. METHODS: Genomic DNA was obtained from 172 patients with
      osteoarthritis and 210 ethnically matched healthy controls. Genotyping for the
      polymorphisms in the PPARgamma gene (Pro12Ala and C1431T) was carried out using
      polymerase chain reaction-restriction fragment length polymorphism. The standard
      Kellgren-Lawrence grading score and the French version of the Western Ontario and
      McMaster Universities Osteoarthritis Index were used to assess the radiological
      and functional severity of the disease. Estimated haplotypes were generated using
      the expectation maximisation algorithm. Genotype and allele frequencies were
      analysed using the chi2 test. RESULTS: Genotype and allele frequencies for either
      polymorphism in the PPARgamma gene did not differ significantly between patients
      with osteoarthritis and controls. Moreover, no significant differences were
      observed after stratification of patients according to age at disease onset,
      radiological or functional severity. Similarly, haplotype analysis of both
      polymorphisms in the PPARgamma gene showed no association of any haplotype with
      susceptibility to, or severity of, osteoarthritis. CONCLUSION: These findings
      suggest that the examined polymorphisms in the PPARgamma gene do not contribute
      to susceptibility to, or severity of, osteoarthritis in the French-Canadian
      population.

PMID- 16973790
TI  - Treatment of mesenteric angina with prolonged anticoagulation in a patient with
      antiphospholipid (Hughes) syndrome and coeliac artery stenosis.

PMID- 16973791
TI  - Evaluation of allele frequencies in the PADI4 gene and anti-cyclic citrullinated
      peptide antibodies of patients with rheumatoid arthritis in a Japanese
      population.

PMID- 16973792
TI  - The changing face of infective endocarditis.
AB  - Infective endocarditis is a disease that continues to evolve in response to
      changing host conditions and other factors.

PMID- 16973793
TI  - Amiodarone induced skin necrosis.

PMID- 16973794
TI  - Double chambered left ventricle in cardiac magnetic resonance imaging.

PMID- 16973795
TI  - Mahaim tachycardia and intravenous adenosine.

PMID- 16973797
TI  - Implantation of a biventricular defibrillator system in a patient with persistent
      left and absent right superior vena cava.

PMID- 16973796
TI  - Giant single coronary artery with terminal fistulous aneurysm: a rare entity.

PMID- 16973798
TI  - Iron chelating in thalassaemia with left ventricular dysfunction.

PMID- 16973799
TI  - Simultaneous combined interventional percutaneous left atrial auricle and atrial
      septal defect closure.

PMID- 16973800
TI  - Aortic valvular endocarditis visualised by 16-row detector multislice computed
      tomography.

PMID- 16973801
TI  - Multiple intracardiac thrombi in a patient with dilated cardiomyopathy.

PMID- 16973802
TI  - Intramyocardial echinococcal cyst demonstrated by multislice computed tomography.

PMID- 16973803
TI  - Pseudoaneurysm of aortocoronary graft secondary to spontaneous late rupture.

PMID- 16973804
TI  - Malignant pectus excavatum.

PMID- 16973805
TI  - Prediction of mortality of patients with suspected heart failure by brain
      natriuretic peptide concentrations > 100 pg/ml: comparison of a clinical model
      with brain natriuretic peptide concentrations.

PMID- 16973806
TI  - Clinical and echocardiographic correlates of plasma osteopontin in the community:
      the Framingham Heart Study.

PMID- 16973807
TI  - Subclinical left ventricular dysfunction in normotensive women with Turner's
      syndrome.

PMID- 16973808
TI  - Raised plasma N-terminal pro-B-type natriuretic peptide concentrations predict
      mortality and cardiac disease in end-stage renal disease.

PMID- 16973809
TI  - Risks of contraception and pregnancy in heart disease.

PMID- 16973810
TI  - Practical management of medical liability for cardiac errors in a hospital
      environment.

PMID- 16973811
TI  - Management of dyslipidaemias.

PMID- 16973812
TI  - Hepatic hydatid cyst rupturing into pericardial cavity.

PMID- 16973813
TI  - Exercise-dependent IGF-I, IGFBPs, and type I collagen changes in human
      peritendinous connective tissue determined by microdialysis.
AB  - Microdialysis studies indicate that mechanical loading of human tendon during
      exercise elevates type I collagen production in tendon. However, the possibility
      that the insertion of microdialysis fibers per se may increase the local collagen
      production due to trauma has not been explored. Insulin-like growth factor I (IGF
      I) and its binding proteins (IGFBPs), which are known to stimulate collagen
      production in animal tendons, may regulate the translation of mechanical loading
      to collagen synthesis. Systemic and tissue levels of IGF-I, IGFBP, and type I
      collagen metabolism markers [procollagen I COOH-terminal propeptide (PICP) and
      COOH-terminal telopeptide of type I collagen] were measured by microdialysis in
      peritendinous tissue of the human Achilles tendon in an exercise group
      (performing a 36-km run, n = 6) and a control group (no intervention, n = 6). An
      increase in local PICP concentration was seen in both groups after 72 h and
      stayed elevated in the exercise group at 96 h (P < 0.05). IGFBP-1 in both serum
      and dialysate increased in the exercise group immediately after exercise (P <
      0.05), whereas IGFBP-3 decreased systemically (P < 0.05). Elevation of local
      IGFBP-4 was observed in both the control and exercise groups after 48 h (P <
      0.05). Total IGF-I did not change in locally or systemically in either group. Our
      results indicate an increased local production of PICP in human peritendinous
      tissue in response to prolonged mechanical loading with part of the increase due
      to trauma from the sampling technique. Care must therefore be emphasized to
      minimize the numbers of insertions with microdialysis. We demonstrated an
      elevation of IGFBP-1 both systemically and peritendinously in response to
      prolonged acute exercise. The local increased collagen synthesis was preceded by
      an elevation of local concentration of IGFBP-4, suggesting that IGFBP-4 may have
      a key role in the IGF-axis effect on the human collagen synthesis in vivo.

PMID- 16973814
TI  - Neural drive to tongue protrudor and retractor muscles following pulmonary C
      fiber activation.
AB  - Hypoglossal (XII) nerve recordings indicate that pulmonary C-fiber (PCF) receptor
      activation reduces inspiratory bursting and triggers tonic discharge. We tested
      three hypotheses related to this observation: 1) PCF receptor activation inhibits
      inspiratory activity in XII branches innervating both tongue protrudor muscles
      (medial branch; XIImed) and retractor muscles (lateral branch; XIIlat); 2)
      reduced XII neurogram amplitude reflects decreased XII motoneuron discharge rate;
      and 3) tonic XII activity reflects recruitment of previously silent motoneurons.
      Phrenic, XIImed, and XIIlat neurograms were recorded in anesthetized, paralyzed,
      and ventilated rats. Capsaicin delivered to the jugular vein reduced phrenic
      bursting at doses of 0.625 and 1.25 mug/kg but augmented bursting at 5 mug/kg.
      All doses reduced inspiratory amplitude in XIImed and XIIlat (P < 0.05), and
      these effects were eliminated following bilateral vagotomy. Single-fiber
      recordings indicated that capsaicin causes individual XII motoneurons to either
      decrease discharge rate (n = 101/153) or become silent (n = 39/153). Capsaicin
      also altered temporal characteristics such that both XIImed and XIIlat
      inspiratory burst onset occurred after the phrenic burst (P < 0.05). Increases in
      tonic discharge after capsaicin were greater in XIImed vs. XIIlat (P < 0.05);
      single-fiber recordings indicated that tonic discharge reflected recruitment of
      previously silent motoneurons. We conclude that PCF receptor activation reduces
      inspiratory XII motoneuron discharge and transiently attenuates neural drive to
      both tongue protrudor and retractor muscles. However, tonic discharge appears to
      be selectively enhanced in tongue protrudor muscles. Accordingly, reductions in
      upper airway stiffness associated with reduced XII burst amplitude may be offset
      by enhanced tonic activity in tongue protrudor muscles.

PMID- 16973815
TI  - How much is there really? Why stereology is essential in lung morphometry.
AB  - Quantitative data on lung structure are essential to set up structure-function
      models for assessing the functional performance of the lung or to make
      statistically valid comparisons in experimental morphology, physiology, or
      pathology. The methods of choice for microscopy-based lung morphometry are those
      of stereology, the science of quantitative characterization of irregular three
      dimensional objects on the basis of measurements made on two-dimensional
      sections. From a practical perspective, stereology is an assumption-free set of
      methods of unbiased sampling with geometric probes, based on a solid mathematical
      foundation. Here, we discuss the pitfalls of lung morphometry and present
      solutions, from specimen preparation to the sampling scheme in multiple stages,
      for obtaining unbiased estimates of morphometric parameters such as volumes,
      surfaces, lengths, and numbers. This is demonstrated on various examples.
      Stereological methods are accurate, efficient, simple, and transparent; the
      precision of the estimates depends on the size and distribution of the sample.
      For obtaining quantitative data on lung structure at all microscopic levels,
      state-of-the-art stereology is the gold standard.

PMID- 16973816
TI  - Interaction of epithelium with mesenchyme affects global features of lung
      architecture: a computer model of development.
AB  - Lung airway morphogenesis is simulated in a simplified diffusing environment that
      simulates the mesenchyme to explore the role of morphogens in airway architecture
      development. Simple rules govern local branching morphogenesis. Morphogen
      gradients are modeled by four pairs of sources and their diffusion through the
      mesenchyme. Sensitivity to lobar architecture and mesenchymal morphogen are
      explored. Even if the model accurately represents observed patterns of local
      development, it could not produce realistic global patterns of lung architecture
      if interaction with its environment was not taken into account, implying that
      reciprocal interaction between airway growth and morphogens in the mesenchyme
      plays a critical role in producing realistic global features of lung
      architecture.

PMID- 16973817
TI  - Neural changes associated with training.

PMID- 16973818
TI  - Counterpoint: active venoconstriction is not important in maintaining or raising
      end-diastolic volume and stroke volume during exercise and orthostasis.

PMID- 16973821
TI  - Comments on Point:Counterpoint series "Active venoconstriction is/is not
      important in maintaining or raising end-diastolic volume and stoke volume during
      exercise and orthostasis.".

PMID- 16973823
TI  - Alterations in cardiac contractile performance and sarcoplasmic reticulum
      function in sucrose-fed rats is associated with insulin resistance.
AB  - Diabetes mellitus (DM) causes the development of a specific cardiomyopathy that
      results from the metabolic derangements present in DM and manifests as cardiac
      contractile dysfunction. Although myocardial dysfunction in Type 1 DM has been
      associated with defects in the function and regulation of the sarcoplasmic
      reticulum (SR), very little is known about SR function in Type 2 DM. Accordingly,
      this study examined whether abnormalities in cardiac contractile performance and
      SR function occur in the prestage of Type 2 DM (i.e., during insulin resistance).
      Sucrose feeding was used to induce whole body insulin resistance, whereas cardiac
      contractile performance was assessed by echocardiography and SR function was
      measured by SR calcium (Ca(2+)) uptake. Sucrose-fed rats exhibited
      hyperinsulinemia, hyperglycemia, and hyperlipidemia relative to control rats.
      Serial echocardiographic assessments in the sucrose-fed rats revealed early
      abnormalities in diastolic function followed by late systolic dysfunction and
      concurrent alterations in myocardial structure. The hearts of the 10-wk sucrose
      fed rats showed depressed SR function demonstrated by a significant reduction in
      SR Ca(2+) uptake. The decline in SR Ca(2+) uptake was associated with a
      significant decrease in the cAMP-dependent protein kinase and Ca(2+)/calmodulin
      dependent protein kinase II-mediated phosphorylation of phospholamban. The
      results show that abnormalities in cardiac contractile performance and SR
      function occur at an insulin-resistant stage before the manifestation of overt
      Type 2 DM.

PMID- 16973824
TI  - Protein kinase C activation inhibits Cav1.3 calcium channel at NH2-terminal
      serine 81 phosphorylation site.
AB  - The Ca(v)1.3 (alpha(1D)) variant of L-type Ca(2+) channels plays a vital role in
      the function of neuroendocrine and cardiovascular systems. In this article, we
      report on the molecular and functional basis of alpha(1D) Ca(2+) channel
      modulation by protein kinase C (PKC). Specifically, we show that the serine 81
      (S81) phosphorylation site at the NH(2)-terminal region plays a critical role in
      alpha(1D) Ca(2+) channel modulation by PKC. The introduction of a negatively
      charged residue at position 81, by converting serine to aspartate, mimicked the
      PKC phosphorylation effect on alpha(1D) Ca(2+) channel. The modulation of
      alpha(1D) Ca(2+) channel by PKC was prevented by dialyzing cells with a 35-amino
      acid peptide mimicking the alpha(1D) NH(2)-terminal region comprising S81. In
      addition, the data revealed that only betaII- and epsilonPKC isozymes are
      implicated in this regulation. These novel findings have significant implications
      in the pathophysiology of alpha(1D) Ca(2+) channel and in the development of PKC
      isozyme-targeted therapeutics.

PMID- 16973826
TI  - Comparison of infarct-derived and control ovine cardiac myofibroblasts in
      culture: response to cytokines and natriuretic peptide receptor expression
      profiles.
AB  - This study investigated whether gene expression profiles of myofibroblasts
      derived from infarcted myocardium differ from normal cardiac fibroblasts. We
      compared the expression of cytoskeletal proteins in cultured ovine cardiac
      fibroblasts derived from infarcted (ID) and noninfarcted ovine myocardium (NID)
      and the levels of expression of the natriuretic peptide receptors (NPR)-A and NPR
      B in response to treatment with transforming growth factor (TGF)-beta1 and/or
      platelet-derived growth factor (PDGF). Transformation of cultured cardiac
      fibroblasts to myofibroblasts, as indicated by alpha-smooth muscle actin and
      vimentin expression, was independent of the presence of TGF-beta1, PDGF, or cell
      origin. ID fibroblasts had higher basal levels than NID fibroblasts of NPR-A (ID:
      58.0 +/- 32.2 arbitrary density units, NID: undetectable), NPR-B (ID: 780 +/-
      155, NID: 330 +/- 38 arbitrary density units) and collagen I (ID: 17.2 +/- 0.5,
      NID: 10.5 +/- 1.7 pg mRNA/mug total RNA, P < 0.05) but lower levels of alpha-SMa
      expression (ID: 50.2 +/- 7.9, NID: 76.9 +/- 3.2 fluorescence units, P < 0.05).
      NPR-A mRNA in ID fibroblasts showed a rapid fourfold increase in response to TGF
      beta1 and/or PDGF at 4 and 2 h, respectively, followed by a profound decline; in
      NID cells, NPR-A mRNA was undetectable. In ID fibroblasts, cytokines reduced NPR
      B mRNA below control levels; in NID fibroblasts, TGF-beta1 and PDGF elicited
      prompt increments in expression: a fourfold increase with TGF-beta1 at 8 h and a
      twofold increase with PDGF at 4 h (P < 0.05). In summary, transformation of
      cardiac fibroblasts to myofibroblasts in culture is independent of cytokine
      treatment. Moreover, whether the cultured cardiac fibroblasts are from infarct
      tissue is a major determinant of NPR expression levels and cytokine responses,
      even after four to five passages.

PMID- 16973825
TI  - Resveratrol attenuates TNF-alpha-induced activation of coronary arterial
      endothelial cells: role of NF-kappaB inhibition.
AB  - Epidemiological studies suggest that Mediterranean diets rich in resveratrol are
      associated with reduced risk of coronary artery disease. However, the mechanisms
      by which resveratrol exerts its cardioprotective effects are not completely
      understood. Because TNF-alpha-induced endothelial activation and vascular
      inflammation play a critical role in vascular aging and atherogenesis, we
      evaluated whether resveratrol inhibits TNF-alpha-induced signal transduction in
      human coronary arterial endothelial cells (HCAECs). We found that TNF-alpha
      significantly increased adhesiveness of the monocytic THP-1 cells to HCAECs, an
      effect that could be inhibited by pretreatment with resveratrol and the NF-kappaB
      inhibitor pyrrolidine dithiocarbamate. Previously, we found that TNF-alpha
      activates NAD(P)H oxidases, and our recent data showed that TNF-alpha-induced
      endothelial activation was prevented by the NAD(P)H oxidase inhibitor apocynin or
      catalase plus SOD. Resveratrol also inhibited H(2)O(2)-induced monocyte
      adhesiveness. Using a reporter gene assay, we found that, in HCAECs, TNF-alpha
      significantly increased NF-kappaB activity, which could be inhibited by
      resveratrol (>50% inhibition at 10(-6) mol/l) and pyrrolidine dithiocarbamate.
      Resveratrol also inhibited TNF-alpha-induced, NF-kappaB-driven luciferase
      expression in rat aortas electroporated with the reporter gene construct. In TNF
      alpha-treated HCAECs, resveratrol (in the submicromolar range) significantly
      attenuated expression of NF-kappaB-dependent inflammatory markers inducible
      nitric oxide synthase, IL-6, bone morphogenetic protein-2, ICAM-1, and VCAM. Thus
      resveratrol at nutritionally relevant concentrations inhibits TNF-alpha-induced
      NF-kappaB activation and inflammatory gene expression and attenuates monocyte
      adhesiveness to HCAECs. We propose that these anti-inflammatory actions of
      resveratrol are responsible, at least in part, for its cardioprotective effects.

PMID- 16973827
TI  - Two novel missense and one novel nonsense CFTR mutations in Iranian males with
      congenital bilateral absence of the vas deferens.
AB  - Congenital bilateral absence of the vas deferens (CBAVD) is a frequent cause of
      obstructive azoospermia. Nearly 75% of men with CBAVD have at least one
      detectable common cystic fibrosis (CF) transmembrane conductance regulator (CFTR)
      mutation. To study the involvement of CFTR mutations in the Iranian population
      with presumed low CF frequency, we analysed 112 Iranian CBAVD males. Three
      Iranian CBAVD males with no clinical CF phenotype indicated by a normal
      karyotype, normal pancreatic function and sweat chloride concentration and no Y
      chromosome microdeletions were studied for CFTR mutations, IVS8-5T mutations and
      M470V exon 10 missense polymorphism. The entire coding sequence of each gene was
      analysed using a combination of the denaturing gradient-gel electrophoresis or by
      single-strand conformation analysis and direct DNA sequencing. Also, 52 fertile
      males were tested as controls to rule out polymorphism. This approach allowed us
      to detect one novel nonsense mutation (K536X) in the nucleotide-binding domain 1
      (NBD1) region and two novel missense mutations (Y122H and T338A) in the M2 and M6
      regions of CFTR gene in our studied population, which were not reported
      previously. Also, the conservation of changed nucleotide and amino acid in
      mutated regions was analysed by aligning with nine different species. K536X
      nonsense mutation (transversion) was found in the first NBD (NBF1), which plays
      an important regulatory role in CFTR function. It was, therefore, considered as a
      severe allele responsible for elevated sweat chloride levels and obstructive
      azoospermia. Because Y122H and T338A mutations were compound heterozygote with
      the IVS8-5T, it is difficult to judge the severity of these mutations and their
      role in the CBAVD phenotype.

PMID- 16973828
TI  - KRAS variation and risk of endometriosis.
AB  - Endometriosis is a common gynaecological disease with symptoms of pelvic pain and
      infertility which affects 7-10% of women in their reproductive years. Activation
      of an oncogenic allele of Kirsten rat sarcoma viral oncogene homologue (KRAS) in
      the reproductive tract of mice resulted in the development of endometriosis. We
      hypothesized that variation in KRAS may influence risk of endometriosis in
      humans. Thirty tagSNPs spanning a region of 60.7 kb across the KRAS locus were
      genotyped using iPLEX chemistry on a MALDI-TOF MassARRAY platform in 959
      endometriosis cases and 959 unrelated controls, and data were analysed for
      association with endometriosis. Genotypes were obtained for most individuals with
      a mean completion rate of 99.1%. We identified six haplotype blocks across the
      KRAS locus in our sample. There were no significant differences between cases and
      controls in the frequencies of individual single-nucleotide polymorphisms (SNPs)
      or haplotypes. We also developed a rapid method to screen for 11 common KRAS and
      BRAF mutations on the Sequenom MassARRAY system. The assay detected all mutations
      previously identified by direct sequencing in a panel of positive controls. No
      germline variants for KRAS or BRAF were detected. Our results demonstrate that
      any risk of endometriosis in women because of common variation in KRAS must be
      very small.

PMID- 16973829
TI  - Cellular cardiomyoplasty: improvement of left ventricular function correlates
      with the release of cardioactive cytokines.
AB  - A growing number of studies are reporting beneficial effects of the
      transplantation of alleged cardiac stem cells into diseased hearts after
      myocardial infarction. However, the mechanisms by which transplanted cells might
      help to promote repair of cardiac tissue are not understood and might involve
      processes different from the differentiation of transplanted cells into
      cardiomyocytes. We have compared the effects exerted by skeletal myoblasts (which
      are not able to form new cardiomyocytes) and ESC-derived cardiomyocytes after
      implantation into infarcted mouse hearts by echocardiographic follow-up and
      histological analysis and related these effects to the release of cardioactive
      cytokines. We found that both cell types led to a long-lasting improvement of
      left ventricle function and to an improvement of tissue architecture. Since no
      relevant amounts of myoblast-derived cells were present in infarcted hearts 28
      days after transplantation, we investigated the release of cytokines from
      implanted cells both before and after transplantation into infarcted hearts. ESC
      derived cardiomyocytes and myoblasts secreted substantial amounts of interleukin
      (IL)-1alpha, IL-6, tumor necrosis factor-beta, and oncostatin M, which strongly
      supported survival and protein synthesis of cultured cardiomyocytes. We postulate
      that the beneficial effects of the transplantation of myoblasts and
      cardiomyocytes on heart function and morphology only partially (if at all) depend
      on the integration of transplanted cells into the myocardium but do depend on the
      release of a complex blend of cardioactive cytokines.

PMID- 16973830
TI  - Concise review: bone morphogenetic protein pleiotropism in neural stem cells and
      their derivatives--alternative pathways, convergent signals.
AB  - Bone morphogenetic proteins (BMPs) are a class of morphogens that are critical
      regulators of the central nervous system (CNS), peripheral nervous system, and
      craniofacial development. Modulation of BMP signaling also appears to be an
      important component of the postnatal stem cell niche. However, describing a
      comprehensive model of BMP actions is complicated by their paradoxical effects in
      precursor cells, which include dorsal specification, promoting proliferation or
      mitotic arrest, cell survival or death, and neuronal or glial fate. In addition,
      in postmitotic neurons BMPs can promote dendritic growth, act as axonal
      chemorepellants, and stabilize synapses. Although many of these responses depend
      on interactions with other incoming signals, some reflect the recruitment of
      distinct BMP signal transduction pathways. In this review, we classify the
      diverse effects of BMPs on neural cells, focus on the known mechanisms that
      specify distinct responses, and discuss the remaining challenges in identifying
      the cellular basis of BMP pleiotropism. Addressing these issues may have
      importance for stem cell mobilization, differentiation, and cell
      integration/survival in reparative therapies.

PMID- 16973831
TI  - Concise review: multipotent mesenchymal stromal cells in blood.
AB  - Peripheral blood-derived multipotent mesenchymal stromal cells circulate in low
      number. They share, most although not all, of the surface markers with bone
      marrow-derived multipotent mesenchymal stromal cells, possess diverse and
      complicated gene expression characteristics, and are capable of differentiating
      along and even beyond mesenchymal lineages. Although their origin and physio
      pathological function are still unclear, their presence in the adult peripheral
      blood might relate to some interesting but controversial subjects in the field of
      adult stem cell biology, such as systemic migration of bone marrow-derived
      multipotent mesenchymal stromal cells and the existence of common hematopoietic
      mesenchymal precursors. In this review, current studies/knowledge about
      peripheral blood-derived multipotent mesenchymal stromal cells is summarized, and
      the above-mentioned topics are discussed.

PMID- 16973832
TI  - Higher expression of transcription targets and components of the nuclear factor
      kappaB pathway is a distinctive feature of umbilical cord blood CD34+ precursors.
AB  - Delayed engraftment, better reconstitution of progenitors, higher thymic
      function, and a lower incidence of the graft-versus-host disease are
      characteristics associated with umbilical cord blood (UCB) transplants, compared
      with bone marrow (BM). To understand the molecular mechanisms causing these
      intrinsic differences, we analyzed the differentially expressed genes between BM
      and UCB hematopoietic stem and progenitor cells (HSPCs). The expressions of
      approximately 10,000 genes were compared by serial analysis of gene expression of
      magnetically sorted CD34(+) cells from BM and UCB. Differential expression of
      selected genes was evaluated by real-time polymerase chain reaction on additional
      CD34(+) samples from BM (n = 22), UCB (n = 9), and granulocyte colony stimulating
      factor-mobilized peripheral blood (n = 6). The overrepresentation of nuclear
      factor-kappaB (NF-kappaB) pathway components and targets was found to be a major
      characteristic of UCB HSPCs. Additional promoter analysis of 41 UCB
      overrepresented genes revealed a significantly higher number of NF-kappaB cis
      regulatory elements (present in 22 genes) than would be expected by chance. Our
      results point to an important role of the NF-kappaB pathway on the molecular and
      functional differences observed between BM and UCB HSPCs. Our study forms the
      basis for future studies and potentially for new strategies to stem cell graft
      manipulation, by specific NF-kappaB pathway modulation on stem cells, prior to
      transplant.

PMID- 16973833
TI  - In vitro expanded cells contributing to rapid severe combined immunodeficient
      repopulation activity are CD34+38-33+90+45RA-.
AB  - Expansion of hematopoietic stem cells could be used clinically to shorten the
      prolonged aplastic phase after umbilical cord blood (UCB) transplantation. In
      this report, we investigated rapid severe combined immunodeficient (SCID)
      repopulating activity (rSRA) 2 weeks after transplantation of CD34(+) UCB cells
      cultured with serum on MS5 stromal cells and in serum- and stroma-free cultures.
      Various subpopulations obtained after culture were studied for rSRA. CD34(+)
      expansion cultures resulted in vast expansion of CD45(+) and CD34(+) cells.
      Independent of the culture method, only the CD34(+)33(+)38(-) fraction of the
      cultured cells contained rSRA. Subsequently, we subfractionated the CD34(+)38(-)
      fraction using stem cell markers CD45RA and CD90. In vitro differentiation
      cultures showed CD34(+) expansion in both CD45RA(-) and CD90(+) cultures, whereas
      little increase in CD34(+) cells was observed in both CD45RA(+) and CD90(-)
      cultures. By four-color flow cytometry, we could demonstrate that CD34(+)38(
      )45RA(-) and CD34(+)38(-)90(+) cell populations were largely overlapping. Both
      populations were able to reconstitute SCID/nonobese diabetic mice at 2 weeks,
      indicating that these cells contained rSRA activity. In contrast, CD34(+)38(
      )45RA(+) or CD34(+)38(-)90(-) cells contributed only marginally to rSRA. Similar
      results were obtained when cells were injected intrafemorally, suggesting that
      the lack of reconstitution was not due to homing defects. In conclusion, we show
      that after in vitro expansion, rSRA is mediated by CD34(+)38(-)90(+)45RA(-)
      cells. All other cell fractions have limited reconstitutive potential, mainly
      because the cells have lost stem cell activity rather than because of homing
      defects. These findings can be used clinically to assess the rSRA of cultured
      stem cells.

PMID- 16973834
TI  - Force measurements of human embryonic stem cell-derived cardiomyocytes in an in
      vitro transplantation model.
AB  - Human embryonic stem cell (hESC)-derived cardiomyocytes have been suggested for
      cardiac cell replacement therapy. However, there are no data on loaded
      contractions developed by these cells and the regulation thereof. We developed a
      novel in vitro transplantation model in which beating cardiomyocytes derived from
      hESCs (line H1) were isolated and transplanted onto noncontractile, ischemically
      damaged ventricular slices of murine hearts. After 2-3 days, transplanted cells
      started to integrate mechanically into the existing matrix, resulting in
      spontaneous movements of the whole preparation. Preparations showed a length
      dependent increase of active tension. In transplanted early beating hESC-derived
      cardiomyocytes, frequency modulation by field stimulation was limited to a small
      range around their spontaneous beating rate. Our data demonstrate that this novel
      in vitro transplantation model is well suited to assess the mechanical properties
      and functional integration of cells suggested for cardiac replacement strategies.

PMID- 16973835
TI  - Notch signaling induces apoptosis in primary human CD34+ hematopoietic progenitor
      cells.
AB  - Notch signaling regulates diverse cell fate decisions during development and is
      reported to promote murine hematopoietic stem cell (HSC) self-renewal. The
      purpose of this study was to define the functional consequences of activating the
      Notch signaling pathway on self-renewal in human HSCs. Subsets of human umbilical
      cord blood CD34(+) cells were retrovirally transduced with the constitutively
      active human Notch 1 intracellular domain (N1ICD). N1ICD-transduced cells
      proliferated to a lesser extent in vitro than cells transduced with vector alone,
      and this was accompanied by a reduction in the percentage and absolute number of
      CD34(+) cell populations, including CD34(+)Thy(+)Lin(-) HSCs. Ectopic N1ICD
      expression inhibited cell cycle kinetics concurrent with an upregulation of p21
      mRNA expression and induced apoptosis. Transduction of cells with HES-1, a known
      transcriptional target of Notch signaling and a mediator of Notch function, had
      no effect on HSC proliferation, indicating that the mechanism of the Notch
      induced effect is HES-1-independent. The results of this study show that
      activation of the Notch signaling pathway has an inhibitory effect on the
      proliferation and survival of human hematopoietic CD34(+) cells populations.
      These findings have important implications for strategies aimed at promoting self
      renewal of human HSCs.

PMID- 16973836
TI  - Mobile phones and driving: a follow-up.

PMID- 16973837
TI  - Relationship between constituent labelling and reporting of tar yields among
      smokers in four countries.
AB  - Countries have adopted different approaches to disseminating cigarette tar,
      nicotine, and carbon monoxide (CO) levels to consumers, with some (e.g. EU member
      states, Canada, Australia, but not the United States) requiring disclosure of
      results from the International Organization for Standardization (ISO) test method
      on packs. Cross-country comparisons can provide insight into how smokers use
      yields when information is presented differently. We examined whether smokers in
      four different countries could recall the tar yield of their brand of cigarettes,
      using data from the third wave of the International Tobacco Control Four Country
      Survey (ITC-4). Of current smokers in the United States, Canada, Australia and
      the United Kingdom, 33.6% gave a numeric response when asked to report the tar
      yield of their brand, whereas 66.4% responded 'I don't know.' American
      participants (9.2%) were less likely than Canadian (28.0%), UK (36.5%) or
      Australian (68.2%) smokers to give an answer, even after controlling for
      sociodemographic and smoking behaviour factors. Constituent labelling policies
      can affect whether smokers report a tar yield for their cigarette brand. Pack
      labelling appears to be useful for conveying information about cigarettes to
      smokers; however, there is an urgent need to develop more meaningful information
      on toxic constituents of cigarette smoke.

PMID- 16973838
TI  - Tests of general relativity from timing the double pulsar.
AB  - The double pulsar system PSR J0737-3039A/B is unique in that both neutron stars
      are detectable as radio pulsars. They are also known to have much higher mean
      orbital velocities and accelerations than those of other binary pulsars. The
      system is therefore a good candidate for testing Einstein's theory of general
      relativity and alternative theories of gravity in the strong-field regime. We
      report on precision timing observations taken over the 2.5 years since its
      discovery and present four independent strong-field tests of general relativity.
      These tests use the theory-independent mass ratio of the two stars. By measuring
      relativistic corrections to the Keplerian description of the orbital motion, we
      find that the "post-Keplerian" parameter s agrees with the value predicted by
      general relativity within an uncertainty of 0.05%, the most precise test yet
      obtained. We also show that the transverse velocity of the system's center of
      mass is extremely small. Combined with the system's location near the Sun, this
      result suggests that future tests of gravitational theories with the double
      pulsar will supersede the best current solar system tests. It also implies that
      the second-born pulsar may not have formed through the core collapse of a helium
      star, as is usually assumed.

PMID- 16973839
TI  - Coherent dynamics of coupled electron and nuclear spin qubits in diamond.
AB  - Understanding and controlling the complex environment of solid-state quantum bits
      is a central challenge in spintronics and quantum information science. Coherent
      manipulation of an individual electron spin associated with a nitrogen-vacancy
      center in diamond was used to gain insight into its local environment. We show
      that this environment is effectively separated into a set of individual proximal
      13C nuclear spins, which are coupled coherently to the electron spin, and the
      remainder of the 13C nuclear spins, which cause the loss of coherence. The
      proximal nuclear spins can be addressed and coupled individually because of
      quantum back-action from the electron, which modifies their energy levels and
      magnetic moments, effectively distinguishing them from the rest of the nuclei.
      These results open the door to coherent manipulation of individual isolated
      nuclear spins in a solid-state environment even at room temperature.

PMID- 16973840
TI  - A combined mitigation/geoengineering approach to climate stabilization.
AB  - Projected anthropogenic warming and increases in CO2 concentration present a
      twofold threat, both from climate changes and from CO2 directly through
      increasing the acidity of the oceans. Future climate change may be reduced
      through mitigation (reductions in greenhouse gas emissions) or through
      geoengineering. Most geoengineering approaches, however, do not address the
      problem of increasing ocean acidity. A combined mitigation/geoengineering
      strategy could remove this deficiency. Here we consider the deliberate injection
      of sulfate aerosol precursors into the stratosphere. This action could
      substantially offset future warming and provide additional time to reduce human
      dependence on fossil fuels and stabilize CO2 concentrations cost-effectively at
      an acceptable level.

PMID- 16973841
TI  - Herpes simplex virus encephalitis in human UNC-93B deficiency.
AB  - Herpes simplex virus-1 (HSV-1) encephalitis (HSE) is the most common form of
      sporadic viral encephalitis in western countries. Its pathogenesis remains
      unclear, as it affects otherwise healthy patients and only a small minority of
      HSV-1-infected individuals. Here, we elucidate a genetic etiology for HSE in two
      children with autosomal recessive deficiency in the intracellular protein UNC
      93B, resulting in impaired cellular interferon-alpha/beta and -lambda antiviral
      responses. HSE can result from a single-gene immunodeficiency that does not
      compromise immunity to most pathogens, unlike most known primary
      immunodeficiencies. Other severe infectious diseases may also reflect monogenic
      disorders of immunity.

PMID- 16973842
TI  - Animal activism: out of control.

PMID- 16973843
TI  - Nonproliferation. Endgame for the U.S.-Russian Nuclear Cities program.

PMID- 16973844
TI  - Archaeology. Claim of oldest New World writing excites archaeologists.

PMID- 16973845
TI  - Astrophysics. Space mission to shine a light on solar flares.

PMID- 16973846
TI  - Infectious disease. Extensively drug-resistant TB gets foothold in South Africa.

PMID- 16973847
TI  - Scientific community. Campaign heats up for WHO Director-General.

PMID- 16973848
TI  - Influenza. Ground the planes during a flu pandemic? Studies disagree.

PMID- 16973849
TI  - Genomics. Poplar tree sequence yields genome double take.

PMID- 16973850
TI  - Astrophysics. Pulsars' gyrations confirm Einstein's theory.

PMID- 16973851
TI  - Paleoanthropology. Mild climate, lack of moderns let last Neandertals linger in
      Gibraltar.

PMID- 16973853
TI  - U.S. graduate education. Foreign enrollment rebounds after 3-year slump.

PMID- 16973852
TI  - Genomics. Microarray data reproduced, but some concerns remain.

PMID- 16973854
TI  - Geochemistry. Radiocarbon dating's final frontier.

PMID- 16973855
TI  - Cell biology. A stressful situation.

PMID- 16973856
TI  - Invasive species. The Galapagos Islands kiss their goat problem goodbye.

PMID- 16973857
TI  - Cuts in Homeland Security research.

PMID- 16973858
TI  - Public access success at PubMed.

PMID- 16973859
TI  - Support for the NIH public access policy.

PMID- 16973860
TI  - Ongoing controversy over Debye's WWII role.

PMID- 16973861
TI  - Bias about climate change.

PMID- 16973862
TI  - Comment on "Large-scale sequence analysis of avian influenza isolates".
AB  - Obenauer et al. (Research Articles, 17 March 2006, p. 1576) reported that the
      influenza A virus PB1-F2 gene is evolving under strong positive selection, as
      documented by an extremely high ratio of the number of nonsynonymous nucleotide
      substitutions to the number of synonymous substitutions (dN/dS). However, we show
      that this observation is likely to be an artifact related to the location of PB1
      F2 in the +1 reading frame of the PB1 gene.

PMID- 16973863
TI  - Social science. Death in Darfur.

PMID- 16973864
TI  - Cell biology. A metabolic push to proliferate.

PMID- 16973865
TI  - Planetary science. Titan's polar weather.

PMID- 16973866
TI  - Microbiology. Mycobacteria's export strategy.

PMID- 16973867
TI  - Chemistry. The organic approach to asymmetric catalysis.

PMID- 16973868
TI  - Structural biology. Dynamic visions of enzymatic reactions.

PMID- 16973869
TI  - Physics. Detecting and controlling electron correlations.

PMID- 16973870
TI  - Vesicle formation at the plasma membrane and trans-Golgi network: the same but
      different.
AB  - An elaborate vesicle transport system supports the active exchange of membranes
      and protein cargo between the plasma membrane and the trans-Golgi network. Many
      observations suggest that highly conserved mechanisms are used in vesicle
      formation and scission. Such similarity is found both at the level of the
      receptor-ligand sequestration process that uses clathrin and associated polymeric
      and monomeric adaptor proteins, and in the machinery used to deform and
      vesiculate lipid membranes.

PMID- 16973871
TI  - Near-field microscopy through a SiC superlens.
AB  - The wave nature of light limits the spatial resolution in classical microscopy to
      about half of the illumination wavelength. Recently, a new approach capable of
      achieving subwavelength spatial resolution, called superlensing, was invented,
      challenging the already established method of scanning near-field optical
      microscopy (SNOM). We combine the advantages of both techniques and demonstrate a
      novel imaging system where the objects no longer need to be in close proximity to
      a near-field probe, allowing for optical near-field microscopy of subsurface
      objects at sub-wavelength-scale lateral resolution.

PMID- 16973873
TI  - Oldest writing in the New World.
AB  - A block with a hitherto unknown system of writing has been found in the Olmec
      heartland of Veracruz, Mexico. Stylistic and other dating of the block places it
      in the early first millennium before the common era, the oldest writing in the
      New World, with features that firmly assign this pivotal development to the Olmec
      civilization of Mesoamerica.

PMID- 16973874
TI  - Probing nanoscale ferroelectricity by ultraviolet Raman spectroscopy.
AB  - We demonstrated that ultraviolet Raman spectroscopy is an effective technique to
      measure the transition temperature (Tc) in ferroelectric ultrathin films and
      superlattices. We showed that one-unit-cell-thick BaTiO3 layers in BaTiO3/SrTiO3
      superlattices are not only ferroelectric (with Tc as high as 250 kelvin) but also
      polarize the quantum paraelectric SrTiO3 layers adjacent to them. Tc was tuned by
      approximately 500 kelvin by varying the thicknesses of the BaTiO3 and SrTiO3
      layers, revealing the essential roles of electrical and mechanical boundary
      conditions for nanoscale ferroelectricity.

PMID- 16973872
TI  - The genome of black cottonwood, Populus trichocarpa (Torr. & Gray).
AB  - We report the draft genome of the black cottonwood tree, Populus trichocarpa.
      Integration of shotgun sequence assembly with genetic mapping enabled chromosome
      scale reconstruction of the genome. More than 45,000 putative protein-coding
      genes were identified. Analysis of the assembled genome revealed a whole-genome
      duplication event; about 8000 pairs of duplicated genes from that event survived
      in the Populus genome. A second, older duplication event is indistinguishably
      coincident with the divergence of the Populus and Arabidopsis lineages.
      Nucleotide substitution, tandem gene duplication, and gross chromosomal
      rearrangement appear to proceed substantially more slowly in Populus than in
      Arabidopsis. Populus has more protein-coding genes than Arabidopsis, ranging on
      average from 1.4 to 1.6 putative Populus homologs for each Arabidopsis gene.
      However, the relative frequency of protein domains in the two genomes is similar.
      Overrepresented exceptions in Populus include genes associated with
      lignocellulosic wall biosynthesis, meristem development, disease resistance, and
      metabolite transport.

PMID- 16973875
TI  - Near-threshold inelastic collisions using molecular beams with a tunable
      velocity.
AB  - Molecular scattering behavior has generally proven difficult to study at low
      collision energies. We formed a molecular beam of OH radicals with a narrow
      velocity distribution and a tunable absolute velocity by passing the beam through
      a Stark decelerator. The transition probabilities for inelastic scattering of the
      OH radicals with Xe atoms were measured as a function of the collision energy in
      the range of 50 to 400 wavenumbers, with an overall energy resolution of about 13
      wavenumbers. The behavior of the cross-sections for inelastic scattering near the
      energetic thresholds was accurately measured, and excellent agreement was
      obtained with cross-sections derived from coupled-channel calculations on ab
      initio computed potential energy surfaces.

PMID- 16973876
TI  - Evidence for a polar ethane cloud on Titan.
AB  - Spectra from Cassini's Visual and Infrared Mapping Spectrometer reveal the
      presence of a vast tropospheric cloud on Titan at latitudes 51 degrees to 68
      degrees north and all longitudes observed (10 degrees to 190 degrees west). The
      derived characteristics indicate that this cloud is composed of ethane and forms
      as a result of stratospheric subsidence and the particularly cool conditions near
      the moon's north pole. Preferential condensation of ethane, perhaps as ice, at
      Titan's poles during the winters may partially explain the lack of liquid ethane
      oceans on Titan's surface at middle and lower latitudes.

PMID- 16973877
TI  - Early reactivation of European rivers during the last deglaciation.
AB  - During the Last Glacial Maximum, the sea-level lowstand combined with the large
      extent of the Fennoscandian and British ice sheets led to the funneling of
      European continental runoff, resulting in the largest river system that ever
      drained the European continent. Here, we show an abrupt and early reactivation of
      the European hydrological cycle at the onset of the last deglaciation, leading to
      intense discharge of the Channel River into the Bay of Biscay. This freshwater
      influx, probably combined with inputs from proglacial or ice-dammed lakes,
      dramatically affected the hydrology of the region, both on land and in the ocean.

PMID- 16973878
TI  - High gamma power is phase-locked to theta oscillations in human neocortex.
AB  - We observed robust coupling between the high- and low-frequency bands of ongoing
      electrical activity in the human brain. In particular, the phase of the low
      frequency theta (4 to 8 hertz) rhythm modulates power in the high gamma (80 to
      150 hertz) band of the electrocorticogram, with stronger modulation occurring at
      higher theta amplitudes. Furthermore, different behavioral tasks evoke distinct
      patterns of theta/high gamma coupling across the cortex. The results indicate
      that transient coupling between low- and high-frequency brain rhythms coordinates
      activity in distributed cortical areas, providing a mechanism for effective
      communication during cognitive processing in humans.

PMID- 16973879
TI  - Caveolin-1 is essential for liver regeneration.
AB  - Liver regeneration is an orchestrated cellular response that coordinates cell
      activation, lipid metabolism, and cell division. We found that caveolin-1 gene
      disrupted mice (cav1-/- mice) exhibited impaired liver regeneration and low
      survival after a partial hepatectomy. Hepatocytes showed dramatically reduced
      lipid droplet accumulation and did not advance through the cell division cycle.
      Treatment of cav1-/- mice with glucose (which is a predominant energy substrate
      when compared to lipids) drastically increased survival and reestablished
      progression of the cell cycle. Thus, caveolin-1 plays a crucial role in the
      mechanisms that coordinate lipid metabolism with the proliferative response
      occurring in the liver after cellular injury.

PMID- 16973880
TI  - C-terminal signal sequence promotes virulence factor secretion in Mycobacterium
      tuberculosis.
AB  - Mycobacterium tuberculosis uses the ESX-1/Snm system [early secreted antigen 6
      kilodaltons (ESAT-6) system 1/secretion in mycobacteria] to deliver virulence
      factors into host macrophages during infection. Despite its essential role in
      virulence, the mechanism of ESX-1 secretion is unclear. We found that the
      unstructured C terminus of the CFP-10 substrate was recognized by Rv3871, a
      cytosolic component of the ESX-1 system that itself interacts with the membrane
      protein Rv3870. Point mutations in the signal that abolished binding of CFP-10 to
      Rv3871 prevented secretion of the CFP-10 (culture filtrate protein, 10
      kilodaltons)/ESAT-6 virulence factor complex. Attachment of the signal to yeast
      ubiquitin was sufficient for secretion from M. tuberculosis cells, demonstrating
      that this ESX-1 signal is portable.

PMID- 16973881
TI  - An alternative bactericidal mechanism of action for lantibiotic peptides that
      target lipid II.
AB  - Lantibiotics are polycyclic peptides containing unusual amino acids, which have
      binding specificity for bacterial cells, targeting the bacterial cell wall
      component lipid II to form pores and thereby lyse the cells. Yet several members
      of these lipid II-targeted lantibiotics are too short to be able to span the
      lipid bilayer and cannot form pores, but somehow they maintain their
      antibacterial efficacy. We describe an alternative mechanism by which members of
      the lantibiotic family kill Gram-positive bacteria by removing lipid II from the
      cell division site (or septum) and thus block cell wall synthesis.

PMID- 16973882
TI  - The dynamic energy landscape of dihydrofolate reductase catalysis.
AB  - We used nuclear magnetic resonance relaxation dispersion to characterize higher
      energy conformational substates of Escherichia coli dihydrofolate reductase. Each
      intermediate in the catalytic cycle samples low-lying excited states whose
      conformations resemble the ground-state structures of preceding and following
      intermediates. Substrate and cofactor exchange occurs through these excited
      substates. The maximum hydride transfer and steady-state turnover rates are
      governed by the dynamics of transitions between ground and excited states of the
      intermediates. Thus, the modulation of the energy landscape by the bound ligands
      funnels the enzyme through its reaction cycle along a preferred kinetic path.

PMID- 16973883
TI  - Pharmacokinetic and pharmacodynamic modeling of recombinant human erythropoietin
      after intravenous and subcutaneous administration in rats.
AB  - The pharmacokinetics (PK) and pharmacodynamics (PD) of recombinant human
      erythropoietin (rHuEPO) were studied in rats after single i.v. and s.c.
      administration at three dose levels (450, 1350, and 4050 IU/kg). The plasma
      concentrations of rHuEPO and its erythropoietic effects including reticulocyte
      (RET), red blood cell (RBC), and hemoglobin (Hb) levels were determined. A two
      compartment model with dual input rate and nonlinear disposition was used to
      characterize the PK of rHuEPO. The catenary indirect response model with several
      compartments reflecting the bone marrow and circulating erythropoietic cells was
      applied. The s.c. doses exhibited slow absorption (T(max) = 12 h) and incomplete
      bioavailability (F = 0.59). In placebo groups, RBC and Hb values gradually
      increased over time with growth of the rats, and the changes in the baselines
      monitored from 8 to 32 weeks of age were described by a nonlinear growth
      function. All doses resulted in dose-dependent increases in RET counts followed
      by an immediate decline below the baseline at around 6 days and returned to the
      predose level in 21-24 days after dosing. A subsequent steady increase of RBC and
      Hb levels followed and reached peaks at 6 days. A tolerance phenomenon observed
      at all dose levels was modeled by a negative feedback inhibition with the
      relative change in Hb level. The PK/PD model well described the erythropoietic
      effects of rHuEPO as well as tolerance, thereby yielding important PD parameters
      (S(max) = 1.87 and SC(50) = 65.37 mIU/ml) and mean lifespans of major
      erythropoietic cell populations in rats.

PMID- 16973884
TI  - A potent human anti-eotaxin1 antibody, CAT-213: isolation by phage display and in
      vitro and in vivo efficacy.
AB  - The CC chemokine, eotaxin1 (CCL11) is an important regulator of eosinophil
      function. A marked accumulation of eosinophils in tissues has been correlated
      with the up-regulation of eotaxin1 expression in several diseases. The potential
      therapeutic value of neutralizing the effects of eotaxin1 in inflammatory
      conditions (including asthma) is under investigation. A human single-chain
      fragment variable antibody that neutralizes human eotaxin1 (CAT-212) was produced
      using antibody phage display and converted to whole antibody IgG4 format (CAT
      213). A novel approach to lead optimization in which the length of the variable
      heavy chain complementarity-determining region 3 was reduced by one amino acid
      resulted in an increase in potency of >1000-fold compared with the parent anti
      eotaxin1 antibody. The optimized antibody binds eotaxin1 with high affinity (80.4
      pM) and specificity. CAT-213 and CAT-212 do not bind or neutralize a range of
      other human proteins including human monocyte chemoattractant protein-1, a
      structurally similar chemokine. CAT-213 neutralizes the ability of eotaxin1 to
      cause an increase in intracellular calcium signaling (with an IC(50) value of
      2.86 nM), migration of CCR3-expressing L1.2 cells (with an IC(50) value of 0.48
      nM), and inhibition of the eotaxin1-evoked shape change of human eosinophils in
      vitro (with an IC(50) of 0.71 nM). Local administration of CAT-213 to mice (1-100
      microg kg(-1)) attenuates dermal eosinophilia induced by human eotaxin1,
      achieving >90% inhibition of eosinophil influx. CAT-213 may therefore be of
      therapeutic value in inhibiting diseases in which eotaxin1 and eosinophils play a
      major role, for example, severe asthma.

PMID- 16973885
TI  - Discovery of novel hippocampal neurogenic agents by using an in vivo stable
      isotope labeling technique.
AB  - Neurogenesis occurs in discrete regions of adult mammalian brain, including the
      subgranular zone of the hippocampus. Hippocampal neurogenesis is enhanced by
      different classes of antidepressants, but screening for neurogenic actions of
      novel antidepressants has been inefficient because of limitations of 5-bromo-2'
      deoxyuridine labeling techniques. We describe an efficient in vivo method for
      measuring hippocampal neurogenesis involving incorporation of the stable isotope,
      (2)H, into genomic DNA during labeling with (2)H(2)O (heavy water). Male rodents
      received 8 to 10% (2)H(2)O in drinking water; DNA was isolated from hippocampal
      progenitor cells or neurons. Label incorporation into progenitor cells of Swiss
      Webster mice revealed subpopulation kinetics: 16% divided with t(1/2) of 2.7
      weeks; the remainder did not divide over 1 year. Progenitor cell proliferation
      rates in mice were strain-dependent. Chronic antidepressant treatment for 3
      weeks, with (2)H(2)O administered during the final week, increased progenitor
      cell proliferation across all the strains tested. Fluoxetine treatment increased
      (2)H incorporation into DNA of gradient-enriched neurons or flow-sorted neuronal
      nuclei 4 weeks after (2)H(2)O labeling, representing the survival and
      differentiation of newly divided cells into neurons. By screening 11 approved
      drugs for effects on progenitor cell proliferation, we detected previously
      unrecognized, dose-dependent enhancement of hippocampal progenitor cell
      proliferation by two statins and the anticonvulsant topiramate. We also confirmed
      stimulatory activity of other anticonvulsants and showed inhibition of progenitor
      cell proliferation by isotretinoin and prednisolone. In conclusion, stable
      isotope labeling is an efficient, high-throughput in vivo method for measuring
      hippocampal progenitor cell proliferation that can be used to screen for novel
      neurogenic drugs.

PMID- 16973886
TI  - Modulation of contractile function through neuropeptide Y receptors during
      development of cardiomyocyte hypertrophy.
AB  - Severity of left ventricular hypertrophy (LVH) correlates with elevated plasma
      levels of neuropeptide Y (NPY) in hypertension. NPY elicits positive and negative
      contractile effects in cardiomyocytes through Y(1) and Y(2) receptors,
      respectively. This study tested the hypothesis that NPY receptor-mediated
      contraction is altered during progression of LVH. Ventricular cardiomyocytes were
      isolated from spontaneously hypertensive rats (SHRs) pre-LVH (12 weeks), during
      development (16 weeks), and at established LVH (20 weeks) and age-matched
      normotensive Wistar Kyoto (WKY) rats. Electrically stimulated (60 V, 0.5 Hz) cell
      shortening was measured using edge detection and receptor expression determined
      at mRNA and protein level. The NPY and Y(1) receptor-selective agonist,
      Leu(31)Pro(34)NPY, stimulated increases in contractile amplitude, which were
      abolished by the Y(1) receptor-selective antagonist, BIBP3226 [R-N(2)-(diphenyl
      acetyl)-N-(4-hydroxyphenyl)methyl-argininamide)], confirming Y(1) receptor
      involvement. Potencies of both agonists were enhanced in SHR cardiomyocytes at 20
      weeks (2300- and 380-fold versus controls). Maximal responses were not
      attenuated. BIBP3226 unmasked a negative contraction effect of NPY, elicited over
      the concentration range (10(-12) to 3 x 10(-9) M) in which NPY and PYY(3-36)
      attenuated the positive contraction effects of isoproterenol, the potencies of
      which were increased in cardiomyocytes from SHRs at 20 weeks (175- and 145-fold
      versus controls); maximal responses were not altered. Expression of NPY-Y(1) and
      NPY-Y(2) receptor mRNAs was decreased (55 and 69%) in left ventricular
      cardiomyocytes from 20-week-old SHRs versus age-matched WKY rats; parallel
      decreases (32 and 80%) were observed at protein level. Enhancement of NPY
      potency, producing (opposing) contractile effects on cardiomyocytes together with
      unchanged maximal response despite reduced receptor number, enables NPY to
      contribute to regulating cardiac performance during compensatory LVH.

PMID- 16973887
TI  - Prostacyclin antagonism reduces pain and inflammation in rodent models of
      hyperalgesia and chronic arthritis.
AB  - The inhibition of prostaglandin (PG) synthesis is at the center of current anti
      inflammatory therapies. Because cyclooxygenase-2 (COX-2) inhibitors and
      nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the formation of multiple
      PGs, there is currently a strong focus on characterizing the role of the
      different PGs in the inflammation process and development of arthritis. Evidence
      to date suggests that both PGE(2) and PGI(2) act as mediators of pain and
      inflammation. Most of the data indicating a role for PGI(2) in this context have
      been generated in animal models of acute pain. Herein, we describe the role of
      PGI(2) in models of osteoarthritis (OA) and rheumatoid arthritis using a highly
      selective PGI(2) receptor (IP, Ptgir) antagonist and IP receptor-deficient mice.
      In the rat OA model using monoiodoacetate injection into the knee joint, the IP
      antagonist reduced pain with an efficacy approaching that of the NSAID
      diclofenac. In a chronic model of inflammatory arthritis, collagen-antibody
      induced arthritis model in mice, IP receptor-deficient mice displayed a 91%
      reduction in arthritis score. Interestingly, pretreatment with the IP [N-[4
      (imidazolidin-2-ylideneamino)-benzyl]-4-methoxy-benzamide] antagonist in this
      model also caused a significant reduction of the symptoms, whereas administration
      of the compound after the initiation of arthritis had no detectable effect. Our
      data indicate that, in addition to its role in acute inflammation, PGI(2) is
      involved in the development of chronic inflammation. The results also suggest
      that the inhibition of PGI(2) synthesis by NSAIDs and COX-2 inhibitors, in
      addition to that of PGE(2), contributes to their efficacy in treating the signs
      of arthritis.

PMID- 16973888
TI  - Ginsenoside-Rh2-induced mitochondrial depolarization and apoptosis are associated
      with reactive oxygen species- and Ca2+-mediated c-Jun NH2-terminal kinase 1
      activation in HeLa cells.
AB  - We show here that Ca(2+) and reactive oxygen species (ROS) are involved in the up
      regulation of c-Jun NH(2)-terminal kinase 1 (JNK1) activity during apoptosis
      induced by ginsenoside Rh2 (G-Rh2) in HeLa, MCF10A-ras, and MCF7 cells. Addition
      of antioxidants such as N-acetyl-l-cysteine or catalase attenuates G-Rh2-induced
      ROS generation, JNK1 activation, and apoptosis. The overexpression of catalase
      down-regulates caspase-3 and JNK1 activities. G-Rh2 treatment of cells results in
      mitochondrial depolarization, second mitochondrial activator of caspase release,
      and translocation of Bax into the mitochondria, and these events are inhibited by
      antioxidants. Ca(2+) is also involved in mitochondrial depolarization during G
      Rh2-induced apoptosis. These results suggest that ROS and Ca(2+) are important
      signaling intermediates leading to stress-activated protein kinase/extracellular
      signal-regulated kinase kinase 1/JNK1 activation and depolarization of the
      mitochondrial membrane potential in G-Rh2-induced apoptosis.

PMID- 16973889
TI  - Transgenic expression of CSF-1 in CSF-1 receptor-expressing cells leads to
      macrophage activation, osteoporosis, and early death.
AB  - CSF-1 is the primary mononuclear phagocyte and osteoclast growth factor.
      Autocrine regulation by CSF-1 has been reported in macrophages during
      inflammatory responses and in neoplastic cells. To investigate whether
      inflammatory disease or neoplasia was the dominant consequence of autocrine
      regulation by CSF-1 in CSF-1 receptor (CSF-1R)-expressing cells, we created mice
      that express CSF-1 under the control of the CSF-1R promoter/first intron driver
      [transgene TgN(Csf1r-Csf1)Ers (TgRC) mice], which have reduced thymic size, a
      short lifetime, and low body weight and develop osteoporosis. In 4-week-old TgRC
      mice, osteoclast numbers are elevated, and macrophage densities are increased in
      bone marrow, spleen, liver, and brain. Cultured TgRC macrophages express CSF-1
      and proliferate without exogenous CSF-1 and in the presence of neutralizing
      antimouse CSF-1 antibody. Compared with macrophages from nontransgenic
      littermates, TgRC macrophages exhibit a stellate morphology, express elevated
      mRNAs for proinflammatory cytokines, and despite a lower, steady-state cytokine
      secretion, secrete elevated levels of inflammatory cytokines in response to LPS,
      indicating that TgRC macrophages are functionally primed through the CSF-1R.
      Thus, autocrine regulation of CSF-1R-expressing cells by CSF-1 leads to a severe
      phenotype that emphasizes the importance of the known, local production of CSF-1
      in inflammatory disease.

PMID- 16973891
TI  - Pivotal advance: vasoactive intestinal peptide inhibits up-regulation of human
      monocyte TLR2 and TLR4 by LPS and differentiation of monocytes to macrophages.
AB  - Vasoactive intestinal peptide (VIP) is an immunoregulatory peptide, which
      inhibits LPS-induced cytokine secretion in myeloid cells and has beneficial
      effects in animal models of inflammatory diseases. We show for the first time
      that VIP decreases LPS-induced up-regulation of TLR2 and TLR4 by human monocytic
      THP1 cells and peripheral blood monocytes (PBM). VIP inhibited up-regulation of
      TLR4 expression in THP1 cells in response to LPS from Escherichia coli or the
      periodontal pathogen Porphyromonas gingivalis within 6 h poststimulation but had
      less of an effect on TLR2. After 24 h, P. gingivalis LPS-stimulated monocytic
      THP1 cells to differentiate into macrophages, which predominantly expressed TLR2,
      and E. coli LPS-stimulated THP1 differentiation to predominantly TLR4-expressing
      macrophages. VIP decreased monocyte differentiation to macrophages induced by LPS
      from either species and also reduced overall TLR2 and TLR4 expression in these
      cells. VIP had a similar effect on human PBM. The transcription factor PU.1
      regulates TLR expression and has a central role in myeloid cell differentiation.
      VIP inhibited the nuclear translocation of PU.1 in LPS-stimulated THP-1
      monocytes. VIP also inhibited the expression of the M-CSF receptor, which is
      regulated by PU.1. In summary, VIP inhibited LPS-induced differentiation of
      monocytes with a concomitant reduction in TLR2 and TLR4 expression. Although
      there was differential induction of TLR expression by LPS from P. gingivalis and
      E. coli, VIP inhibited the action of both of these LPS types on monocytes. The
      mechanism of action of VIP on monocyte differentiation may be via inhibition of
      the transcription factor PU.1.

PMID- 16973890
TI  - Effects of LPS-mediated bystander activation in the innate immune system.
AB  - LPS induces dendritic cell (DC) activation, but the precise in vivo mechanism is
      unclear since DCs express low levels of TLR4. Here, it is shown that DCs can be
      activated in response to LPS through a bystander mechanism. This result was
      obtained using chimeric mice reconstituted with LPS-responsive and nonresponsive
      bone marrow cells. Thus, after indirect in vivo conditioning by LPS, bystander
      activated DCs (LPS nonresponsive) up-regulated CD86. This up-regulation occurred
      even when LPS-responsive cells were MyD88 deficient. Functional analysis
      demonstrated that in vivo LPS conditioning endowed both the LPS-responsive and
      bystander cells with the ability to produce IFN-gamma in response to TLR9
      stimulation in vitro. IFN-gamma production was also shown to be important for
      enhanced T-bet gene expression but not important for up-regulation of CD86. To
      investigate aspects of the mechanism, we used intracellular cytokine staining and
      found that NKDCs were responsible for at least some of the IFN-gamma production.
      Thus, our in vivo results demonstrated that bacterial LPS can bridge activation
      of various cellular populations of the innate immune system through a bystander
      mechanism.

PMID- 16973892
TI  - Restriction for gene insertion within the Lactococcus lactis Ll.LtrB group II
      intron.
AB  - The Ll.LtrB intron, from the low G+C gram-positive bacterium Lactococcus lactis,
      was the first bacterial group II intron shown to splice and mobilize in vivo. The
      detailed retrohoming and retrotransposition pathways of Ll.LtrB were studied in
      both L. lactis and Escherichia coli. This bacterial retroelement has many
      features that would make it a good gene delivery vector. Here we report that the
      mobility efficiency of Ll.LtrB expressing LtrA in trans is only slightly affected
      by the insertion of fragments <100 nucleotides within the loop region of domain
      IV. In contrast, Ll.LtrB mobility efficiency is drastically decreased by the
      insertion of foreign sequences >1 kb. We demonstrate that the inhibitory effect
      caused by the addition of expression cassettes on Ll.LtrB mobility efficiency is
      not sequence specific, and not due to the expression, or the toxicity, of the
      cargo genes. Using genetic screens, we demonstrate that in order to maintain
      intron mobility, the loop region of domain IV, more specifically domain IVb, is
      by far the best region to insert foreign sequences within Ll.LtrB. Poisoned
      primer extension and Northern blot analyses reveal that Ll.LtrB constructs
      harboring cargo sequences splice less efficiently, and show a significant
      reduction in lariat accumulation in L. lactis. This suggests that cargo
      containing Ll.LtrB variants are less stable. These results reveal the potential,
      yet limitations, of the Ll.LtrB group II intron to be used as a gene delivery
      vector, and validate the random insertion approach described in this study to
      create cargo-containing Ll.LtrB variants that are mobile.

PMID- 16973893
TI  - Two independently selected capping ribozymes share similar substrate
      requirements.
AB  - We report the isolation and characterization of a second capping ribozyme, called
      6.17. This ribozyme has substrate requirements that are very similar to a
      previously isolated capping ribozyme called Iso6. Both ribozymes promote capping
      and cap exchange reactions with a broad range of nucleotide substrates. The
      ribozymes mediate a reaction where the terminal phosphate of the nucleotide
      substrate attacks the alpha-phosphate found at the ribozyme's 5' terminus. This
      reaction involves the release of pyrophosphate during capping or a nucleotide
      during cap exchange. The second-order rate constants for 6.17 and Iso6 depend
      strongly on the length of the phosphate group found on the nucleotide substrate.
      Nucleoside diphosphates or triphosphates are efficiently utilized, while
      monophosphates are used approximately 20-fold less efficiently by both ribozymes.
      These ribozymes also have rates that increase as pH is decreased. Despite these
      similarities, the ribozymes are not identical and 6.17 performs optimally when
      incubated with divalent magnesium ions, while Iso6 displays a preference for
      calcium ions. Further, the ribozymes have globally different secondary
      structures; 6.17 has a complicated pseudoknot structure consisting of five
      helical elements, while Iso6 likely consists of four helical elements. We
      hypothesize that capping proceeds via an invariant phosphate dependent mechanism
      that imposes a nearly identical "catalytic fingerprint" on these two distinct
      ribozymes.

PMID- 16973894
TI  - Mouse microRNA profiles determined with a new and sensitive cloning method.
AB  - MicroRNAs (miRNAs) are noncoding RNA molecules of 21 to 24 nt that regulate the
      expression of target genes in a post-transcriptional manner. Although evidence
      indicates that miRNAs play essential roles in embryogenesis, cell differentiation
      and pathogenesis of human diseases, extensive miRNA profiling in cells or tissues
      has been hampered by the lack of sensitive cloning methods. Here we describe a
      highly efficient profiling method, termed miRNA amplification profiling (mRAP),
      as well as its application both to mouse embryos at various developmental stages
      and to adult mouse organs. A total of 77,436 Small-RNA species was sequenced,
      with 11,776 of these sequences found to match previously described miRNAs. With
      the use of a newly developed computational prediction algorithm, we further
      identified 229 independent candidates for previously unknown miRNAs. The
      expression of some of these candidate miRNAs was confirmed by northern blot
      analysis and whole-mount in situ hybridization. Our data thus indicate that the
      total number of miRNAs in vertebrates is larger than previously appreciated and
      that the expression of these molecules is tightly controlled in a tissue- and
      developmental stage-specific manner.

PMID- 16973895
TI  - Isolation and characterization of the TIGA genes, whose transcripts are induced
      by growth arrest.
AB  - We report here the isolation of 44 genes that are upregulated after serum
      starvation and/or contact inhibition. These genes have been termed TIGA, after
      Transcript Induced by Growth Arrest. We found that there are two kinds of G0
      phases caused by serum starvation, namely, the shallow G0 (or G0/G1) and the deep
      G0 phases. The shallow G0 is induced by only a few hours of serum starvation,
      while deep G0 is generated after 3 days of serum starvation. We propose that
      mammalian cells enter deep G0 through a G0 gate, which is only opened on the
      third day of serum starvation. TIGA1, one of the uncharacterized TIGA genes,
      encodes a homolog of cyanate permease of bacteria and localizes in mitochondria.
      This suggests that Tiga1 is involved in the inorganic ion transport and
      metabolism needed to maintain the deep G0 phase. Ectopic expression of TIGA1
      inhibited not only tumor cell proliferation but also anchorage-independent growth
      of cancer cell lines. A microsatellite marker, ENDL-1, allowed us to detect loss
      of heterozygosity around the TIGA1 gene region (5q21-22). Further analysis of the
      TIGA genes we have identified here may help us to better understand the
      mechanisms that regulate the G0 phase.

PMID- 16973896
TI  - Transcriptome response to heavy metal stress in Drosophila reveals a new zinc
      transporter that confers resistance to zinc.
AB  - All organisms are confronted with external variations in trace element abundance.
      To elucidate the mechanisms that maintain metal homeostasis and protect against
      heavy metal stress, we have determined the transcriptome responses in Drosophila
      to sublethal doses of cadmium, zinc, copper, as well as to copper depletion.
      Furthermore, we analyzed the transcriptome of a metal-responsive transcription
      factor (MTF-1) null mutant. The gene family encoding metallothioneins, and the
      ABC transporter CG10505 that encodes a homolog of 'yeast cadmium factor' were
      induced by all three metals. Zinc and cadmium responses have similar features:
      genes upregulated by both metals include those for glutathione S-transferases
      GstD2 and GstD5, and for zinc transporter-like proteins designated ZnT35C and
      ZnT63C. Several of the metal-induced genes that emerged in our study are
      regulated by the transcription factor MTF-1. mRNA studies in MTF-1 overexpressing
      or null mutant flies and in silico search for metal response elements (binding
      sites for MTF-1) confirmed novel MTF-1 regulated genes such as ferritins, the ABC
      transporter CG10505 and the zinc transporter ZnT35C. The latter was analyzed in
      most detail; biochemical and genetic approaches, including targeted mutation,
      indicate that ZnT35C is involved in cellular and organismal zinc efflux and plays
      a major role in zinc detoxification.

PMID- 16973897
TI  - Human replication protein A unfolds telomeric G-quadruplexes.
AB  - G-quadruplex structures inhibit telomerase activity and must be disrupted for
      telomere elongation during S phase. It has been suggested that the replication
      protein A (RPA) could unwind and maintain single-stranded DNA in a state amenable
      to the binding of telomeric components. We show here that under near
      physiological in vitro conditions, human RPA is able to bind and unfold G
      quadruplex structures formed from a 21mer human telomeric sequence. Analyses by
      native gel electrophoresis, cross-linking and fluorescence resonance energy
      transfer indicate the formation of both 1:1 and 2:1 complexes in which G
      quadruplexes are unfolded. In addition, quadruplex opening by hRPA is much faster
      than observed with the complementary DNA, demonstrating that this protein
      efficiently unfolds G-quartets. A two-step mechanism accounting for the binding
      of hRPA to G-quadruplexes is proposed. These data point to the involvement of
      hRPA in regulation of telomere maintenance.

PMID- 16973898
TI  - DNA bending by bHLH charge variants.
AB  - We wish to understand the role of electrostatics in DNA stiffness and bending.
      The DNA charge collapse model suggests that mutual electrostatic repulsions
      between neighboring phosphates significantly contribute to DNA stiffness.
      According to this model, placement of fixed charges near the negatively charged
      DNA surface should induce bending through asymmetric reduction or enhancement of
      these inter-phosphate repulsive forces. We have reported previously that charged
      variants of the elongated basic-leucine zipper (bZIP) domain of Gcn4p bend DNA in
      a manner consistent with this charge collapse model. To extend this result to a
      more globular protein, we present an investigation of the dimeric basic-helix
      loop-helix (bHLH) domain of Pho4p. The 62 amino acid bHLH domain has been
      modified to position charged amino acid residues near one face of the DNA double
      helix. As observed for bZIP charge variants, DNA bending toward appended cations
      (away from the protein:DNA interface) is observed. However, unlike bZIP proteins,
      DNA is not bent away from bHLH anionic charges. This finding can be explained by
      the structure of the more globular bHLH domain which, in contrast to bZIP
      proteins, makes extensive DNA contacts along the binding face.

PMID- 16973899
TI  - A novel archaeal regulatory protein, Sta1, activates transcription from viral
      promoters.
AB  - While studying gene expression of the rudivirus SIRV1 in cells of its host, the
      hyperthermophilic crenarchaeon Sulfolobus, a novel archaeal transcriptional
      regulator was isolated. The 14 kDa protein, termed Sulfolobus transcription
      activator 1, Sta1, is encoded on the host chromosome. Its activating effect on
      transcription initiation from viral promoters was demonstrated in in vitro
      transcription experiments using a reconstituted host system containing the RNA
      polymerase, TATA-binding protein (TBP) and transcription factor B (TFB). Most
      pronounced activation was observed at low concentrations of either of the two
      transcription factors, TBP or TFB. Sta1 was able to bind viral promoters
      independently of any component of the host pre-initiation complex. Two binding
      sites were revealed by footprinting, one located in the core promoter region and
      the second approximately 30 bp upstream of it. Comparative modeling, NMR and
      circular dichroism of Sta1 indicated that the protein contained a winged helix
      turn-helix motif, most probably involved in DNA binding. This strategy of the
      archaeal virus to co-opt a host cell regulator to promote transcription of its
      genes resembles eukaryal virus-host relationships.

PMID- 16973900
TI  - Radiographic adaptations to the stress of high-level rock climbing in junior
      athletes: a 5-year longitudinal study of the German Junior National Team and a
      group of recreational climbers.
AB  - BACKGROUND: Radiographic adaptations and changes in adult climbers are a well
      known fact, but few data are available for young climbers. HYPOTHESIS:
      Radiographic adaptations have been shown for highly active young climbers. The
      question arises whether these adaptations may lead to an early onset of
      osteoarthrosis in the fingers. STUDY DESIGN: Cohort study; Level of evidence, 2.
      METHODS: Ten members of the German Junior National Team (GJNT; 21.0 +/- 1.6
      years) and 10 recreational climbers (RC; 19.9 +/- 1.9 years) were examined using
      a standard questionnaire and radiographs of the hand. For comparison, radiographs
      of 12 young nonclimbers (control group [CG]) were evaluated. RESULTS: The
      climbing level of GJNT increased significantly during the 5-year evaluation
      period (P < .01) and was significantly higher than that of the RC (1999: P < .01,
      2004: P < .01). There was no increase in finger contractures or finger joint
      capsular width during the 5 years. Stress reactions were found in 8 of 10 of GJNT
      (1999 and 2004) and increased in RC from 2 of 10 (1999) to 3 of 10 (2004). No
      osteoarthrotic changes were found in 2004. There was no significant difference
      for the Barnett-Nordin Index between GJNT, RC, and CG. Years of climbing (P <
      .01), participation in climbing competitions (P < .01), hours of training per
      week (P < .01), number of training units per week (P < .05), and climbing level
      (2004) (P < .01) were significant factors for development of radiographic stress
      reaction in all athletes (GJNT and RC). CONCLUSION: Intensive training and
      climbing leads to adaptive reactions such as cortical hypertrophy and broadened
      joint bases in the fingers. Nevertheless, osteoarthrotic changes are rare in
      young climbers. A longer follow-up is necessary to evaluate whether these
      adaptive stress reactions may lead to an early onset of osteoarthritis.

PMID- 16973901
TI  - Achilles tendon elongation after rupture repair: a randomized comparison of 2
      postoperative regimens.
AB  - BACKGROUND: A few prospective controlled trials comparing early functional
      rehabilitation after Achilles tendon repair and non-operative immobilization have
      been reported. HYPOTHESES: There is no difference in Achilles tendon elongation
      between early motion and immobilization after Achilles tendon repair. Tendon
      elongation does not correlate with the clinical outcome. STUDY DESIGN: Randomized
      clinical trial; Level of evidence, 2. METHODS: Fifty patients with acute Achilles
      tendon rupture were randomized postoperatively to receive either early movement
      of the ankle between neutral and plantar flexion in a brace for 6 weeks or
      immobilization in tension using a below-knee cast with the ankle in a neutral
      position for 6 weeks. Full weightbearing was allowed after 3 weeks in both
      groups. Standardized radiographs to measure previously placed radiographic
      markers were taken on the first day postoperatively and at 1, 3, 6, 12, 24 weeks
      postoperatively, with the final radiograph a mean of 60 (SD, 6.4) weeks
      postoperatively. The outcome was assessed at the 3-month and final checkups by
      the clinical scoring method described by Leppilahti et al and included subjective
      factors and objective factors. RESULTS: Tendon elongation occurred in both groups
      but was somewhat less in the early motion group (median 2 mm in the early motion
      group vs median 5 mm in the cast group a mean of 60 weeks postoperatively, P =
      .054). The elongation curves first rose and then slowly fell in both groups. The
      patients who had less elongation achieved a better clinical outcome (rho = -.42,
      P = .017). Tendon elongation did not correlate significantly with age, body mass
      index, or isokinetic peak torques. CONCLUSION: Achilles tendon elongation was
      somewhat less in the early motion group and correlated with the clinical outcome
      scores. We recommend early functional postoperative treatment after Achilles
      rupture repair.

PMID- 16973902
TI  - Pitching biomechanics as a pitcher approaches muscular fatigue during a simulated
      baseball game.
AB  - BACKGROUND: The effects of approaching muscular fatigue on pitching biomechanics
      are currently unknown. As a pitcher fatigues, pitching mechanics may change,
      leading to a decrease in performance and an increased risk of injury. HYPOTHESIS:
      As a pitcher approaches muscular fatigue, select pitching biomechanical variables
      will be significantly different than they were before muscular fatigue. STUDY
      DESIGN: Controlled laboratory study. METHODS: Ten collegiate baseball pitchers
      threw 15 pitches per inning for 7 to 9 innings off an indoor throwing mound
      during a simulated baseball game. A pitching session ended when each pitcher felt
      he could no longer continue owing to a subjective perception of muscular fatigue.
      A 6-camera 3D automatic digitizing system collected 200-Hz video data. Twenty
      kinematic and 11 kinetic variables were calculated throughout 4 phases of the
      pitch. A repeated-measure analysis of variance (P < .01) was used to compare
      biomechanical variables between innings. RESULTS: Compared with the initial 2
      innings, as a pitcher approached muscular fatigue during the final 2 innings he
      was able to pitch, there was a significant decrease in ball velocity, and the
      trunk was significantly closer to a vertical position. There were no other
      significant differences in kinematics or kinetics variables. CONCLUSION: The
      relatively few differences observed imply that pitching biomechanics remained
      remarkably similar between collegiate starting pitchers who threw between 105 and
      135 pitches for 7 to 9 innings and approached muscular fatigue. CLINICAL
      RELEVANCE: This study did not support the idea that there is an increase in
      shoulder and elbow forces and torques as muscular fatigue is approached. It is
      possible that if a pitcher remained in a fatigued state for a longer period of
      time, additional changes in pitching mechanics may occur and the risk of injury
      may increase.

PMID- 16973903
TI  - Meniscal repair with biofix arrows: results after 4.7 years' follow-up.
AB  - BACKGROUND: Absorbable meniscus arrows have, since they were introduced in 1993,
      become a common all-inside technique in meniscal repair. Potential advantages are
      conserving the meniscus, simplifying the surgical technique, reducing operating
      time, and reducing the risk of neurovascular damage. Despite extensive use all
      over the world, few long-term follow-up studies have been published. HYPOTHESIS:
      Meniscus arrows have, based on published material, a rate of success around 80%
      to 90%. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The Biofix
      arrow fixation technique was used in 123 patients in need of meniscal repair from
      January 1997 to December 2002 at our hospital. The patients underwent an
      interview by phone, mail, or e-mail during autumn 2004 that included questions
      about reoperation and Lysholm score. In addition, the operative charts were
      reviewed. RESULTS: There were 118 patients (96%) available for the questionnaire,
      and 45 of these (38%) had had reoperations done because of meniscal rerupture
      during the follow-up period. Another 3 patients were waiting for meniscal
      reoperations. In addition, the charts of 2 of those unavailable for the study
      showed that they had been reoperated, resulting in a total of 41% verified
      failures. The Lysholm score for the whole study group at follow-up was 85 (range,
      36-100). The mean Lysholm score for those who had a second operation was 81
      (range, 36-100), and it was 88 (range, 55-100) for the others (P = .009). The
      mean time between primary operation and reoperation was 17 months (range, 1-75
      months). Mean postoperative follow-up was 4.7 years (range, 1.8-7.7 years).
      CONCLUSION: Meniscal repair with Biofix arrows has an unacceptably low rate of
      success.

PMID- 16973904
TI  - Oxidized phospholipids stimulate angiogenesis via autocrine mechanisms,
      implicating a novel role for lipid oxidation in the evolution of atherosclerotic
      lesions.
AB  - Angiogenesis is a common feature observed in advanced atherosclerotic lesions. We
      hypothesized that oxidized phospholipids (OxPLs), which accumulate in
      atherosclerotic vessels can stimulate angiogenesis. We found that oxidized 1
      palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) stimulated the
      formation of sprouts from endothelial cell spheroids and promoted growth of
      capillaries into Matrigel plugs in mice. OxPLs stimulated expression of vascular
      endothelial growth factor (VEGF) in vivo and in several normal and tumor cell
      types in vitro. In addition, OxPAPC upregulated cyclooxygenase (COX)-2 and
      interleukin (IL)-8. COX-2 inhibitors, as well as blocking antibodies to IL-8
      suppressed activation of sprouting by OxPAPC. We conclude that OxPAPC stimulates
      angiogenesis via autocrine mechanisms involving VEGF, IL-8, and COX-2-generated
      prostanoids. Our data suggest that accumulation of OxPLs may contribute to
      increased growth of blood capillaries in advanced lesions, thus leading to
      progression and destabilization of atherosclerotic plaques.

PMID- 16973905
TI  - APOE4-VLDL inhibits the HDL-activated phosphatidylinositol 3-kinase/Akt Pathway
      via the phosphoinositol phosphatase SHIP2.
AB  - Endothelial cell dysfunction and apoptosis are critical in the pathogenesis of
      atherosclerotic cardiovascular disease (CVD). Both endothelial cell apoptosis and
      atherosclerosis are reduced by high-density lipoprotein (HDL). Low HDL levels
      increase the risk of CVD and are also a key characteristic of the metabolic
      syndrome. The apolipoprotein E4 (APOE4) allele also increases the risk of
      atherosclerosis and CVD. We previously demonstrated that the antiapoptotic
      activity of HDL is inhibited by APOE4 very-low-density lipoprotein (APOE4-VLDL)
      in endothelial cells, an effect similar to reducing the levels of HDL. Here we
      establish the intracellular mechanism by which APOE4-VLDL inhibits the
      antiapoptotic pathway activated by HDL. We show that APOE4-VLDL diminishes the
      phosphorylation of Akt by HDL but does not alter phosphorylation of c-Jun N
      terminal kinase, p38, or Src family kinases by HDL. Furthermore APOE4-VLDL
      inhibits Akt phosphorylation by reducing the phosphatidylinositol 3-kinase
      product phosphatidylinositol-(3,4,5)-triphosphate (PI[3,4,5]P3). We further
      demonstrate that APOE4-VLDL reduces PI(3,4,5)P3, through the phosphoinositol
      phosphatase SHIP2, and not through PTEN. SHIP2 is already implicated as an
      independent risk factor for type II diabetes, hypertension and obesity, which are
      also all components of the metabolic syndrome and independent risk factors for
      CVD. Significantly, the association between CVD and type 2 diabetes or
      hypertension is further increased by the APOE4 allele. Therefore the activation
      of SHIP2 by APOE4-VLDL, with the subsequent inhibition of the HDL/Akt pathway, is
      a novel and significant biological mechanism and may be a critical intermediate
      by which APOE4 increases the risk of atherosclerotic CVD.

PMID- 16973906
TI  - Protein kinase A-mediated acceleration of the stretch activation response in
      murine skinned myocardium is eliminated by ablation of cMyBP-C.
AB  - Beta-adrenergic agonists induce protein kinase A (PKA) phosphorylation of the
      cardiac myofilament proteins myosin binding protein C (cMyBP-C) and troponin I
      (cTnI), resulting in enhanced systolic function, but the relative contributions
      of cMyBP-C and cTnI to augmented contractility are not known. To investigate
      possible roles of cMyBP-C in this response, we examined the effects of PKA
      treatment on the rate of force redevelopment and the stretch activation response
      in skinned ventricular myocardium from both wild-type (WT) and cMyBP-C null
      (cMyBP-C(-/-)) myocardium. In WT myocardium, PKA treatment accelerated the rate
      of force redevelopment and the stretch activation response, resulting in a
      shorter time to the peak of delayed force development when the muscle was
      stretched to a new isometric length. Ablation of cMyBP-C accelerated the rate of
      force redevelopment and stretch activation response to a degree similar to that
      observed in PKA treatment of WT myocardium; however, PKA treatment had no effect
      on the rate of force development and the stretch activation response in null
      myocardium. These results indicate that ablation of cMyBP-C and PKA treatment of
      WT myocardium have similar effects on cross-bridge cycling kinetics and suggest
      that PKA phosphorylation of cMyBP-C accelerates the rate of force generation and
      thereby contributes to the accelerated twitch kinetics observed in living
      myocardium during beta-adrenergic stimulation.

PMID- 16973907
TI  - Adenylyl cyclase isoform-selective regulation of vascular smooth muscle
      proliferation and cytoskeletal reorganization.
AB  - Compartmentation of cAMP signaling been demonstrated to be attributable to the
      structural association of protein kinase A (PKA) (via association with A-kinase
      anchoring proteins [AKAPs]) with phosphodiesterase and AKAP-dependent effector
      molecules. However, other mechanisms contributing to compartmentalization have
      not been rigorously explored, including the possibility that different isoforms
      of adenylyl cyclase (AC) may be functionally "compartmentalized" because of
      differential association with tethering or signaling molecules. To this end, we
      examined the effect of adenoviral transduction of representative AC isoforms
      (AC1, AC2, AC5, and AC6) on cellular cAMP production, PKA activation,
      extracellular signal-regulated kinase (ERK) activation, cell doubling and
      proliferation, as well as arborization responses (an index of cAMP-mediated
      cytoskeletal re-organization) in vascular smooth muscle cells. When isoforms were
      expressed at levels to achieve comparable forskolin-stimulated AC activity, only
      gene transfer of AC6 significantly enhanced PKA-dependent vasodilator-stimulated
      phosphoprotein (VASP) phosphorylation and arborization responses. Treatment of
      control cells, which express AC6 endogenously, as well as vascular smooth
      overexpressing the AC6 isoform with small interfering RNA directed against AC6,
      significantly suppressed both isoproterenol-stimulated cAMP accumulation and
      arborization. Notably, the selective effects of AC6 expression were abrogated in
      the presence of phosphodiesterase suppression. In contrast, only the expression
      of AC1 enhanced forskolin-stimulated association of ERK with AC, demonstrated by
      coimmuno-isolation of ERK with Flag-tagged AC1, but not with Flag-tagged AC6. To
      determine whether these isoform-selective effects of AC were unique to
      differentiated and morphologically compartmentalized vascular smooth muscle cells
      or were a general property of these isoforms, we examined the consequence of
      expression of these various isoforms in human embryonic kidney (HEK) cells.
      Indeed, we observed similar isoform-dependent association of AC1 with ERK,
      activation of ERK by stimulation of AC1 with forskolin, and AC1-dependent
      lengthening of doubling time, indicating that these properties of AC1 are cell
      autologous and likely result from AC1-dependent protein-protein interactions. In
      aggregate, these findings suggest that isoform-selective signaling complexes
      likely contribute to various functional consequences of cAMP elevation in
      vascular smooth muscle cells.

PMID- 16973908
TI  - Human pulmonary valve progenitor cells exhibit endothelial/mesenchymal plasticity
      in response to vascular endothelial growth factor-A and transforming growth
      factor-beta2.
AB  - In situ analysis of fetal semilunar valve leaflets has revealed cells
      coexpressing endothelial and mesenchymal markers along the endothelium, with
      diminished frequency seen in adult valves. To determine whether such cells are
      progenitor cells, we isolated clonal populations from human pulmonary valves. The
      clones expressed endothelial markers but showed potential to further
      differentiate into endothelium in response to vascular endothelial growth factor
      (VEGF)-A. When exposed to transforming growth factor (TGF)-beta2, individual
      clones adopted a mesenchymal phenotype to varying degrees and expressed markers
      of endothelial to mesenchymal transformation (EMT). Both VEGF- and TGFbeta2
      induced phenotypic changes were partially reversible, indicating the plasticity
      of these cells. When challenged with VEGF or TGFbeta2, a hierarchy of
      endothelial/mesenchymal potential could be seen among the clonal populations:
      cells initially closer to an endothelial phenotype showed a strong response to
      TGFbeta2 that could be inhibited by VEGF, whereas cells closer to a mesenchymal
      phenotype responded to TGFbeta2 but were resistant to endothelial-inducing
      effects of VEGF. These findings suggest the presence of bipotential valve
      progenitor cells with ability to differentiate into either endothelial or
      interstitial cells of the valve leaflet. Understanding the differentiation
      potential and function of these cells may be important for understanding heart
      valve disease and may also be applied to current paradigms for creating tissue
      engineered heart valves.

PMID- 16973909
TI  - Novel mechanism of endothelial nitric oxide synthase activation mediated by
      caveolae internalization in endothelial cells.
AB  - Caveolin-1, the caveolae scaffolding protein, binds to and negatively regulates
      eNOS activity. As caveolin-1 also regulates caveolae-mediated endocytosis after
      activation of the 60-kDa albumin-binding glycoprotein gp60 in endothelial cells,
      we addressed the possibility that endothelial NO synthase (eNOS)-dependent NO
      production was functionally coupled to caveolae internalization. We observed that
      gp60-induced activation of endocytosis increased NO production within 2 minutes
      and up to 20 minutes. NOS inhibitor N(G)-nitro-L-arginine (L-NNA) prevented the
      NO production. To determine the role of caveolae internalization in the mechanism
      of NO production, we expressed dominant-negative dynamin-2 mutant (K44A) or
      treated cells with methyl-beta-cyclodextrin. Both interventions inhibited
      caveolae-mediated endocytosis and NO generation induced by gp60. We determined
      the role of signaling via Src kinase in the observed coupling of endocytosis to
      eNOS activation. Src activation induced the phosphorylation of caveolin-1, Akt
      and eNOS, and promoted dissociation of eNOS from caveolin-1. Inhibitors of Src
      kinase and Akt also prevented NO production. In isolated perfused mouse lungs,
      gp60 activation induced NO-dependent vasodilation, whereas the response was
      attenuated in eNOS(-/-) or caveolin-1(-/-) lungs. Together, these results
      demonstrate a critical role of caveolae-mediated endocytosis in regulating eNOS
      activation in endothelial cells and thereby the NO-dependent vasomotor tone.

PMID- 16973910
TI  - How do myocytes tell right from left?

PMID- 16973911
TI  - Homocysteine and cardiovascular disease: is HDL the link?

PMID- 16973912
TI  - Collateral artery growth: making the most of what you have.

PMID- 16973913
TI  - Trafficking of G protein-coupled receptors.
AB  - G protein-coupled receptors (GPCRs) play an integral role in the signal
      transduction of an enormous array of biological phenomena, thereby serving to
      modulate at a molecular level almost all components of human biology. This role
      is nowhere more evident than in cardiovascular biology, where GPCRs regulate such
      core measures of cardiovascular function as heart rate, contractility, and
      vascular tone. GPCR/ligand interaction initiates signal transduction cascades,
      and requires the presence of the receptor at the plasma membrane. Plasma membrane
      localization is in turn a function of the delivery of a receptor to and removal
      from the cell surface, a concept defined most broadly as receptor trafficking.
      This review illuminates our current view of GPCR trafficking, particularly within
      the cardiovascular system, as well as highlights the recent and provocative
      finding that components of the GPCR trafficking machinery can facilitate GPCR
      signaling independent of G protein activation.

PMID- 16973914
TI  - The peristaltic reflex induced by short-chain fatty acids is mediated by
      sequential release of 5-HT and neuronal CGRP but not BDNF.
AB  - Short-chain fatty acids (SCFAs) accelerate colonic transit. This study examined
      whether this action was mediated by activation of the peristaltic reflex. SCFAs
      (acetate, butyrate, or propionate) were applied to the central compartment of a
      three-compartment flat-sheet preparation of the rat middle to distal colon. The
      release of serotonin (5-HT), brain-derived neurotrophic factor (BDNF), and CGRP
      was measured in all three compartments. Ascending contraction and descending
      relaxation were measured in the orad and caudad compartments. The addition of
      SCFAs at physiological to supraphysiological concentrations (0.5-100 mM) to the
      central compartment elicited concentration-dependent ascending contraction and
      descending relaxation (EC50 approximately 5 mM). At this concentration, SCFAs
      induced an 8- to 11-fold increase in 5-HT release and a 2- to 3-fold increase in
      CGRP release in the central compartment only. They had no effect on BDNF release.
      CGRP release was inhibited by a 5-HT4 but not a 5-HT3 receptor antagonist.
      Ascending contraction and descending relaxation were also inhibited by 5-HT4 and
      by CGRP receptor antagonists added to the central compartment. 5-HT and CGRP
      release, as well as ascending contraction and descending relaxation induced by
      mechanical stimulation of the mucosa (2-8 strokes), were significantly augmented
      by 1 mM acetate. Acetate (1 mM) also doubled propulsive velocity in isolated
      whole segments of the guinea pig colon. In conclusion, chemical stimulation of
      the mucosa by SCFAs triggers a peristaltic reflex mediated by the release of 5-HT
      from mucosal cells and activation of 5-HT4 receptors on sensory CGRP-containing
      nerve terminals. This SCFA-induced peristaltic pathway augments the peristaltic
      reflex elicited by mechanical stimulation of the mucosa.

PMID- 16973915
TI  - Expression and functional features of NaCT, a sodium-coupled citrate transporter,
      in human and rat livers and cell lines.
AB  - In this article, we report on the expression and function of a Na(+)-coupled
      transporter for citrate, NaCT, in human and rat liver cell lines and in primary
      hepatocytes from the rat liver. We also describe the polarized expression of this
      transporter in human and rat livers. Citrate uptake in human liver cell lines
      HepG2 and Huh-7 was obligatorily dependent on Na+. The uptake system showed a
      preference for citrate over other intermediates of the citric acid cycle and
      exhibited a Michaelis constant of approximately 6 mM for citrate. The transport
      activity was stimulated by Li+, and the activation was associated with a marked
      increase in substrate affinity. Citrate uptake in rat liver cell line MH1C1 was
      also Na+ dependent and showed a preference for citrate. The Michaelis constant
      for citrate was approximately 10 microM. The transport activity was inhibited by
      Li+. Primary hepatocytes from the rat liver also showed robust activity for Na+
      coupled citrate uptake, with functional features similar to those described in
      the rat liver cell line. Immunolabeling with a specific anti-NaCT antibody showed
      exclusive expression of the transporter in the sinusoidal membrane of hepatocytes
      in human and rat livers. This constitutes the first report on the expression and
      function of NaCT in liver cells.

PMID- 16973916
TI  - Polyamines are required for phospholipase C-gamma1 expression promoting
      intestinal epithelial restitution after wounding.
AB  - Intestinal mucosal restitution occurs by epithelial cell migration, rather than
      by proliferation, to reseal superficial wounds after injury. Polyamines are
      essential for the stimulation of intestinal epithelial cell (IEC) migration
      during restitution in association with their ability to regulate Ca2+
      homeostasis, but the exact mechanism by which polyamines induce cytosolic free
      Ca2+ concentration ([Ca2+]cyt) remains unclear. Phospholipase C (PLC)-gamma1
      catalyzes the formation of inositol (1,4,5)-trisphosphate (IP3), which is
      implicated in the regulation of [Ca2+]cyt by modulating Ca2+ store mobilization
      and Ca2+ influx. The present study tested the hypothesis that polyamines are
      involved in PLC-gamma1 activity, regulating [Ca2+]cyt and cell migration after
      wounding. Depletion of cellular polyamines by alpha-difluoromethylornithine
      inhibited PLC-gamma1 expression in differentiated IECs (stable Cdx2-transfected
      IEC-6 cells), as indicated by substantial decreases in levels of PLC-gamma1 mRNA
      and protein and its enzyme product IP3. Polyamine-deficient cells also displayed
      decreased [Ca2+]cyt and inhibited cell migration. Decreased levels of PLC-gamma1
      by treatment with U-73122 or transfection with short interfering RNA specifically
      targeting PLC-gamma1 also decreased IP3, reduced resting [Ca2+]cyt and Ca2+
      influx after store depletion, and suppressed cell migration in control cells. In
      contrast, stimulation of PLC-gamma1 by 2,4,6-trimethyl-N-(meta-3
      trifluoromethylphenyl)-benzenesulfonamide induced IP3, increased [Ca2+]cyt, and
      promoted cell migration in polyamine-deficient cells. These results indicate that
      polyamines are absolutely required for PLC-gamma1 expression in IECs and that
      polyamine-mediated PLC-gamma1 signaling stimulates cell migration during
      restitution as a result of increased [Ca2+]cyt.

PMID- 16973917
TI  - The VSL#3 probiotic formula induces mucin gene expression and secretion in
      colonic epithelial cells.
AB  - Several studies have stressed the importance of the microbiota in the maintenance
      of the gastrointestinal epithelium. Administration of probiotic bacteria,
      supplements composed of microbiota constituents, was previously shown to diminish
      symptoms in patients suffering from inflammatory bowel diseases. This raises the
      possibility that probiotics may play an active role in enhancing the intestinal
      barrier at the mucosal surface. In this study, we investigated whether the
      clinically tested VSL#3 probiotic formula and/or its secreted components can
      augment the protective mucus layer in vivo and in vitro. For in vivo studies,
      Wistar rats were orally administered the probiotic mixture VSL#3 on a daily basis
      for seven days. After treatment, basal luminal mucin content increased by 60%. In
      addition, we exposed isolated rat colonic loops to the VSL#3 probiotic formula,
      which significantly stimulated colonic mucin (MUC) secretion and MUC2 gene
      expression; however, MUC1 and MUC3 gene expression were only slightly elevated.
      The effect of the VSL#3 mucin secretagogue was also tested in vitro by use of LS
      174T colonic epithelial cells. In contrast to the animal studies, cultured cells
      incubated with VSL#3 bacteria did not exhibit increased mucin secretion. However,
      the bacterial secreted products contained in the conditioned media stimulated a
      remarkable mucin secretion effect. Among the three bacterial groups
      (Lactobacilli, Bifidobacteria, and Streptococci) contained in VSL#3, the
      Lactobacillus species were the strongest potentiator of mucin secretion in vitro.
      A preliminary characterization of the putative mucin secretagogue suggested that
      it was a heat-resistant soluble compound, which is not sensitive to protease and
      DNase treatment. These findings contribute to a better understanding of the
      complex and beneficial interaction between colonic epithelial cells and
      intestinal bacteria.

PMID- 16973918
TI  - Estrogen rapidly modulates mustard oil-induced visceral hypersensitivity in
      conscious female rats: A role of CREB phosphorylation in spinal dorsal horn
      neurons.
AB  - This study investigated the effect of sex hormones on mustard oil (MO)-induced
      visceral hypersensitivity in female rats and analyzed possible involved signaling
      pathways. Female rats, either intact or ovariectomized (OVX), were prepared for
      abdominal muscle electromyography in response to colorectal distension after
      intracolonic instillation of MO. The effect of MO intracolonic sensitization was
      evaluated in intact rats, OVX rats, and OVX rats pretreated with a single
      injection of 17beta-estradiol (E), progesterone (P), E+P, or vehicle. cAMP
      responsive element-binding protein (CREB) and phosphorylated CREB (pCREB) were
      detected in the superficial dorsal horn of L6 and S1 in MO or mineral oil-treated
      OVX rats with/without colorectal distension and estrogen replacement. The distal
      colorectum was removed for histological evaluation of inflammatory severity in MO
      treated intact or OVX rats. The MO-treated rats had significantly higher
      visceromotor reflex than controls (enhanced visceral hypersensitivity), whereas
      OVX eliminated this hypersensitivity. After a single injection of E or E+P, the
      rats rapidly restored MO-induced visceral hypersensitivity within 2 h. Estrogen
      also rapidly induced a dose-dependent increase in pCREB expression in the
      superficial dorsal horn neurons in MO-treated, but not mineral oil-treated, OVX
      rats. The present study suggests that estrogen can rapidly modulate visceral
      hypersensitivity induced by MO intracolonic instillation in conscious female
      rats, which may involve spinal activation of the cAMP response element-mediated
      gene induction pathway.

PMID- 16973919
TI  - Atrial natriuretic factor negatively modulates secretin intracellular signaling
      in the exocrine pancreas.
AB  - We previously reported that atrial natriuretic factor (ANF) stimulates pancreatic
      secretion through NPR-C receptors coupled to PLC and potentiates secretin
      response without affecting cAMP levels. In the present study we sought to
      establish the intracellular signaling mechanism underlying the interaction
      between both peptides. In isolated pancreatic acini 100 nM ANF abolished cAMP
      accumulation evoked by any dose of secretin. Lower doses of ANF (1 fM, 1 pM, 1
      and 10 nM) dose dependently reduced EC50 secretin-evoked cAMP. Although ANF
      failed to affect cAMP stimulated by amthamine (selective H2 agonist) or
      isoproterenol (beta-adrenergic agonist), it abolished VIP-induced cAMP formation.
      ANF inhibitory effect was prevented by U-73122 (PLC inhibitor) and GF-109203X
      (PKC inhibitor) but unaltered by PKG and nitric oxide synthase inhibition,
      supporting that the PLC/PKC pathway mediated the effect. ANF response was
      mimicked by cANP (4-23 amide) and abolished by pertussis toxin, strongly
      supporting NPR-C receptor activation. In vivo studies showed that ANF at 0.5
      microg x kg(-1) x h(-1) enhanced secretion stimulated by 1 U x kg(-1) x h(-1)
      secretin but at 1 and 2 microg x kg(-1) x h(-1) it abolished secretin response.
      However, ANF at such doses failed to modify the secretion evoked by carbachol or
      CCK. Present results show that ANF negatively modulated secretin secretory
      response and intracellular signaling through the activation of NPR-C receptors
      coupled to the PLC/PKC pathway. Furthermore, the finding that ANF also inhibited
      VIP-evoked cAMP supports a selective modulation of class II G-protein coupled
      receptors by ANF. Present findings suggest that ANF may play a protective role by
      reducing secretin response to avoid overstimulation.

PMID- 16973920
TI  - Development of a simple high-throughput screening protocol based on biosynthetic
      activity of Mycobacterium tuberculosis glutamine synthetase for the
      identification of novel Inhibitors.
AB  - A high-throughput screening protocol has been developed for Mycobacterium
      tuberculosis glutamine synthetase by quantitative estimation of inorganic
      phosphate. The K(m) values determined at pH 6.8 are 22 mM for L-glutamic acid,
      0.75 mM for NH(4)Cl, 3.25 mM for MgCl(2), and 2.5 mM for adenosine triphosphate.
      The K(m) value for glutamine is affected significantly by the increase in pH of
      assay buffer. At the saturating level of the substrate, the enzyme activity at pH
      6.8 and 25 degrees C is found to be linear up to 3 h. The reduction of enzyme
      activity is negligible even in presence of 10% DMSO. The Z' factor and signal-to
      noise ratio are found to be 0.75 and 6.18, respectively, when the enzyme is used
      at 62.5 microg/ml concentration. The IC(50) values obtained at pH 6.8 for both L
      methionine S-sulfoximine and DL-phosphothriacin are 500 microM and 30 microM,
      respectively, which is lowest compared to the values obtained at other pH levels.
      The Beckman Coulter high-throughput screening platform was found to take 5 h 9
      min to complete the screening of 60 plates. For each assay plate, a replica plate
      is used to normalize the data. Screening of 1164 natural product
      fractions/extracts and synthetic molecules from an in-house library was able to
      identify 12 samples as confirmed hits. Altogether, the validation data from
      screening of a small set of an in-house library coupled with Z' and signal-to
      noise values indicate that the protocol is robust for high-throughput screening
      of a diverse chemical library.

PMID- 16973921
TI  - Rapid generation of single-tumor spheroids for high-throughput cell function and
      toxicity analysis.
AB  - Spheroids are widely used in biology because they provide an in vitro 3
      dimensional (3D) model to study proliferation, cell death, differentiation, and
      metabolism of cells in tumors and the response of tumors to radiotherapy and
      chemotherapy. The methods of generating spheroids are limited by size
      heterogeneity, long cultivation time, or mechanical accessibility for higher
      throughput fashion. The authors present a rapid method to generate single
      spheroids in suspension culture in individual wells. A defined number of cells
      ranging from 1000 to 20,000 were seeded into wells of poly-HEMA-coated, 96-well,
      round-or conical-bottom plates in standard medium and centrifuged for 10 min at
      1000 g. This procedure generates single spheroids in each well within a 24-h
      culture time with homogeneous sizes, morphologies, and stratification of
      proliferating cells in the rim and dying cells in the core region. Because a
      large number of tumor cell lines form only loose aggregates when cultured in 3D,
      the authors also performed a screen for medium additives to achieve a switch from
      aggregate to spheroid morphology. Small quantities of the basement membrane
      extract Matrigel, added to the culture medium prior to centrifugation, most
      effectively induced compact spheroid formation. The compact spheroid morphology
      is evident as early as 24 h after centrifugation in a true suspension culture.
      Twenty tumor cell lines of different lineages have been used to successfully
      generate compact, single spheroids with homogenous size in 96-well plates and are
      easily accessible for subsequent functional analysis.

PMID- 16973922
TI  - High-throughput screening: update on practices and success.
AB  - High-throughput screening (HTS) has become an important part of drug discovery at
      most pharmaceutical and many biotechnology companies worldwide, and use of HTS
      technologies is expanding into new areas. Target validation, assay development,
      secondary screening, ADME/Tox, and lead optimization are among the areas in which
      there is an increasing use of HTS technologies. It is becoming fully integrated
      within drug discovery, both upstream and downstream, which includes increasing
      use of cell-based assays and high-content screening (HCS) technologies to achieve
      more physiologically relevant results and to find higher quality leads. In
      addition, HTS laboratories are continually evaluating new technologies as they
      struggle to increase their success rate for finding drug candidates. The material
      in this article is based on a 900-page HTS industry report involving 54 HTS
      directors representing 58 HTS laboratories and 34 suppliers.

PMID- 16973923
TI  - An ultraefficient affinity-based high-throughout screening process: application
      to bacterial cell wall biosynthesis enzyme MurF.
AB  - The authors describe the discovery of a new class of inhibitors to an essential
      Streptococcus pneumoniae cell wall biosyn-thesis enzyme, MurF, by a novel
      affinity screening method. The strategy involved screening very large mixtures of
      diverse small organic molecules against the protein target on the basis of
      equilibrium binding, followed by iterative ultrafiltration steps and ligand
      identification by mass spectrometry. Hits from any affinity-based screening
      method often can be relatively nonselective ligands, sometimes referred to as
      "nuisance" or "promiscuous" compounds. Ligands selective in their binding
      affinity for the MurF target were readily identified through electronic
      subtraction of an empirically determined subset of promiscuous compounds in the
      library without subsequent selectivity panels. The complete strategy for
      discovery and identification of novel specific ligands can be applied to all
      soluble protein targets and a wide variety of ligand libraries.

PMID- 16973924
TI  - AT1 receptor blockers for cognition decline after cardiac surgery?

PMID- 16973925
TI  - Prevention of stroke in patients with ischemic stroke or transient ischemic
      attack.

PMID- 16973927
TI  - Aspirin and stroke severity.

PMID- 16973929
TI  - ATP increases intracellular calcium in supraoptic neurons by activation of both
      P2X and P2Y purinergic receptors.
AB  - ATP increases intracellular calcium concentration ([Ca(2+)](i)) in supraoptic
      nucleus (SON) neurons in hypothalamo-neurohypophyseal system explants loaded with
      the Ca(2+)-sensitive dye, fura 2-AM. Involvement of P2X purinergic receptors
      (P2XR) in this response was anticipated, because ATP stimulation of vasopressin
      release from hypothalamo-neurohypophyseal system explants required activation of
      P2XRs, and activation of P2XRs induced an increase in [Ca(2+)](i) in dissociated
      SON neurons. However, the ATP-induced increase in [Ca(2+)](i) persisted after
      removal of Ca(2+) from the perifusate ([Ca(2+)](o)). This suggested involvement
      of P2Y purinergic receptors (P2YR), because P2YRs induce Ca(2+) release from
      intracellular stores, whereas P2XRs are Ca(2+)-permeable ion channels. Depletion
      of [Ca(2+)](i) stores with thapsigargin (TG) prevented the ATP-induced increase
      in [Ca(2+)](i) in zero, but not in 2 mM [Ca(2+)](o), indicating that both Ca(2+)
      influx and release of intracellular Ca(2+) contribute to the ATP response. Ca(2+)
      influx was partially blocked by cadmium, indicating a contribution of voltage
      gated Ca(2+) channels. PPADS (pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic
      acid), and iso-PPADS, P2XR antagonists, attenuated, but did not abolish, the ATP
      induced increase in [Ca(2+)](i). Combined treatment with PPADS or iso-PPADS and
      TG prevented the response. A cocktail of P2YR agonists consisting of UTP, UDP,
      and 2-methylthio-ADP increased [Ca(2+)](i) (with or without tetrodotoxin) that
      was markedly attenuated by TG. 2-Methylthio-ADP alone induced consistent and
      larger increases in [Ca(2+)](i) than UTP or UDP. MRS2179, a specific P2Y(1)R
      antagonist, eliminated the response to ATP in zero [Ca(2+)](o). Thus, both P2XR
      and P2YR participate in the ATP-induced increase in [Ca(2+)](i), and the P2Y(1)R
      subtype is more prominent than P2Y(2)R, P2Y(4)R, or P2Y(6)R in SON.

PMID- 16973930
TI  - Type IV carbonic anhydrase is present in the gills of spiny dogfish (Squalus
      acanthias).
AB  - Physiological and biochemical studies have provided indirect evidence for a
      membrane-associated carbonic anhydrase (CA) isoform, similar to mammalian type IV
      CA, in the gills of dogfish (Squalus acanthias). This CA isoform is linked to the
      plasma membrane of gill epithelial cells by a glycosylphosphatidylinositol anchor
      and oriented toward the plasma, such that it can catalyze the dehydration of
      plasma HCO(3)(-) ions. The present study directly tested the hypothesis that CA
      IV is present in dogfish gills in a location amenable to catalyzing plasma
      HCO(3)(-) dehydration. Homology cloning techniques were used to assemble a 1,127
      base pair cDNA that coded for a deduced protein of 306 amino acids. Phylogenetic
      analysis suggested that this protein was a type IV CA. For purposes of
      comparison, a second cDNA (1,107 base pairs) was cloned from dogfish blood; it
      encoded a deduced protein of 260 amino acids that was identified as a cytosolic
      CA through phylogenetic analysis. Using real-time PCR and in situ hybridization,
      mRNA expression for the dogfish type IV CA was detected in gill tissue and
      specifically localized to pillar cells and branchial epithelial cells that
      flanked the pillar cells. Immunohistochemistry using a polyclonal antibody raised
      against rainbow trout type IV CA revealed a similar pattern of CA IV
      immunoreactivity and demonstrated a limited degree of colocalization with Na(+)
      K(+)-ATPase immunoreactivity. The presence and localization of a type IV CA
      isoform in the gills of dogfish is consistent with the hypothesis that branchial
      membrane-bound CA with an extracellular orientation contributes to CO(2)
      excretion in dogfish by catalyzing the dehydration of plasma HCO(3)(-) ions.

PMID- 16973931
TI  - Transient receptor potential ion channels as participants in thermosensation and
      thermoregulation.
AB  - Living organisms must evaluate changes in environmental and internal temperatures
      to mount appropriate physiological and behavioral responses conducive to
      survival. Classical physiology has provided a wealth of information regarding the
      specialization of thermosensory functions among subclasses of peripheral sensory
      neurons and intrinsically thermosensitive neurons within the hypothalamus.
      However, until recently, the molecular mechanisms by which these cells carry out
      thermometry have remained poorly understood. The demonstration that certain ion
      channels of the transient receptor potential (TRP) family can be activated by
      increases or decreases in ambient temperature, along with the recognition of
      their heterogeneous expression patterns and heterogeneous temperature
      sensitivities, has led investigators to evaluate these proteins as candidate
      endogenous thermosensors. Much of this work has involved one specific channel,
      TRP vanilloid 1 (TRPV1), which is both a receptor for capsaicin and related
      pungent vanilloid compounds and a "heat receptor," capable of directly
      depolarizing neurons in response to temperatures >42 degrees C. Evidence for a
      contribution of TRPV1 to peripheral thermosensation has come from
      pharmacological, physiological, and genetic approaches. In contrast, although
      capsaicin-sensitive mechanisms clearly influence core body temperature
      regulation, the specific contribution of TRPV1 to this process remains a matter
      of debate. Besides TRPV1, at least six additional thermally sensitive TRP
      channels have been identified in mammals, and many of these also appear to
      participate in thermosensation. Moreover, the identification of invertebrate TRP
      channels, whose genetic ablation alters thermally driven behaviors, makes it
      clear that thermosensation represents an evolutionarily conserved role of this
      ion channel family.

PMID- 16973932
TI  - Excretion and conservation of glycerol, and expression of aquaporins and
      glyceroporins, during cold acclimation in Cope's gray tree frog Hyla
      chrysoscelis.
AB  - Cope's gray tree frog Hyla chrysoscelis accumulates glycerol during cold
      acclimation. We hypothesized that, during this process, gray tree frogs adjust
      renal filtration and/or reabsorption rates to retain accumulated glycerol. During
      cold acclimation, plasma concentrations of glycerol rose >200-fold, to 51 mmol/l.
      Although fractional water reabsorption decreased, glomerular filtration rate
      (GFR) and, consequently, urine flow were <5% of warm levels, and fractional
      glycerol reabsorption increased. In contrast, dehydrated frogs increased
      fractional water reabsorption, decreased GFR, and did not accumulate glycerol. We
      hypothesized that expression of proteins from the aquaporin (AQP)/glyceroporin
      (GLP) family was associated with changing patterns of water and glycerol
      movement. We cloned the cDNA for three such proteins, quantified mRNA expression
      in nine tissues using real-time quantitative PCR, and functionally characterized
      them using a Xenopus oocyte expression system. HC-1, an AQP1-like water channel
      conferring low glycerol permeability, is expressed ubiquitously in warm- and cold
      acclimated tissues. HC-2, a water channel most similar to AQP2, is primarily
      expressed in organs of osmoregulation. HC-3, which is most similar to AQP3, is
      functionally characterized as a GLP, with low permeability to water but high
      permeability to glycerol. Aspects of expression levels and functional
      characteristics varied between cold and warm conditions for each of the three
      AQPs, suggesting a complex pattern of involvement in osmoregulation related to
      thermal acclimation.

PMID- 16973933
TI  - Baroreflex control of renal sympathetic nerve activity during air-jet stress in
      rats.
AB  - The effects of acute emotional stress on the sympathetic component of the
      arterial baroreceptor reflex have not yet been described in conscious animals and
      humans. Arterial pressure (AP) and renal sympathetic nerve activity (RSNA) were
      simultaneously recorded in 11 conscious rats before and during exposure to a mild
      environmental stressor (jet of air). Baroreflex function curves relating AP and
      RSNA were constructed by fitting a sigmoid function to RSNA and AP measured
      during sequential nitroprusside and phenylephrine administrations. Stress
      increased mean AP from 112 +/- 2 to 124 +/- 2 mmHg, heart rate from 381 +/- 10 to
      438 +/- 18 beats/min, and RSNA from 0.80 +/- 0.14 to 1.49 +/- 0.23 microV. The
      RSNA-AP relationship was shifted toward higher AP values, and its maximum gain
      was significantly (P < 0.01) increased from 9.0 +/- 1.3 to 16.2 +/- 2.1
      normalized units (NU)/mmHg. The latter effect was secondary to an increase (P <
      0.01) in the range of the RSNA variation from 285 +/- 33 to 619 +/- 59 NU. In
      addition, the operating range of the reflex was increased (P < 0.01) from 34 +/-
      2 to 41 +/- 3 mmHg. The present study indicates that in rats, the baroreflex
      control of RSNA is sensitized and operates over a larger range during emotional
      stress, which suggests that renal vascular tone, and possibly AP, are very
      efficiently controlled by the sympathetic nervous system under this condition.

PMID- 16973934
TI  - Increased expression of HIF-1alpha, nNOS, and VEGF in the cerebral cortex of
      anemic rats.
AB  - This study tested the hypothesis that specific hypoxic molecules, including
      hypoxia-inducible factor-1alpha (HIF-1alpha), neuronal nitric oxide synthase
      (nNOS), and vascular endothelial growth factor (VEGF), are upregulated within the
      cerebral cortex of acutely anemic rats. Isoflurane-anesthetized rats underwent
      acute hemodilution by exchanging 50% of their blood volume with pentastarch.
      Following hemodilution, mean arterial pressure and arterial Pa(O(2)) values did
      not differ between control and anemic rats while the hemoglobin concentration
      decreased to 57 +/- 2 g/l. In anemic rats, cerebral cortical HIF-1alpha protein
      levels were increased, relative to controls (1.7 +/- 0.5-fold, P < 0.05). This
      increase was associated with an increase in mRNA levels for VEGF, erythropoietin,
      CXCR4, iNOS, and nNOS (P < 0.05 for all), but not endothelial NOS. Cerebral
      cortical nNOS and VEGF protein levels were increased in anemic rats, relative to
      controls (2.0 +/- 0.2- and 1.5 +/- 0.4-fold, respectively, P < 0.05 for both).
      Immunohistochemistry demonstrated increased HIF-1alpha and VEGF staining in
      perivascular regions of the anemic cerebral cortex and an increase in the number
      of nNOS-positive cerebral cortical cells (3.2 +/- 1.0-fold, P < 0.001). The nNOS
      positive cells costained with the neuronal marker, Neu-N, but not with the
      astrocytic marker glial fibrillary acidic protein (GFAP). These nNOS-positive
      neurons frequently sent axonal projections toward cerebral blood vessels.
      Conversely, VEGF immunostaining colocalized with both neuronal (NeuN) and
      astrocytic markers (GFAP). In conclusion, acute normotensive, normoxemic
      hemodilution increased the levels of HIF-1alpha protein and mRNA for HIF-1
      responsive molecules. nNOS and VEGF protein levels were also increased within the
      cerebral cortex of anemic rats at clinically relevant hemoglobin concentrations.

PMID- 16973935
TI  - Neonatal immune challenge exacerbates experimental colitis in adult rats:
      potential role for TNF-alpha.
AB  - Early life events and childhood infections have been associated with the
      development and onset of inflammatory bowel disease in adulthood. However, the
      consequences of neonatal infection in the development and severity of colitis are
      not established. We investigated the effects of a neonatal (postnatal day 14) or
      juvenile (postnatal day 28) immune challenge with LPS on 2,4,6
      trinitrobenzenesulfonic acid (TNBS)-induced damage and weight loss, as well as on
      food intake and body temperature in adult rats. Neonatally (n)LPS-treated rats
      developed more severe colitis than control animals, reflected in a greater loss
      of weight and a significantly increased macroscopic tissue damage score. These
      findings were associated with a hypothermic response after TNBS treatment in nLPS
      rats, but not in neonatally saline-treated rats receiving TNBS. These differences
      were not seen after TNBS in rats that had received LPS on postnatal day 28.
      Plasma corticosterone was measured as an index of adult hypothalamic-pituitary
      adrenal (HPA) axis activation as was TNF-alpha, a proinflammatory cytokine
      associated with inflammatory bowel disease. Four days after TNBS treatment,
      plasma corticosterone was unaltered in all groups; however, TNF-alpha was
      significantly increased in adult TNBS-treated rats that had LPS as neonates
      compared with all other groups. In conclusion, neonatal, but not later, exposure
      to LPS produces long-term exacerbations in the development of colitis in adults.
      This change is independent of HPA axis activation 4 days after TNBS treatment but
      is associated with increased circulating TNF-alpha, suggestive of an exaggerated
      immune response in adults exposed to neonatal infection.

PMID- 16973936
TI  - Hepatic and muscle insulin action during late pregnancy in the dog.
AB  - We evaluated the effects of physiologic increases in insulin on hepatic and
      peripheral glucose metabolism in nonpregnant (NP) and pregnant (P; 3rd trimester)
      conscious dogs (n = 9 each) using tracer and arteriovenous difference techniques
      during a hyperinsulinemic euglycemic clamp. Insulin was initially (-150 to 0 min)
      infused intraportally at a basal rate. During 0-120 min (Low Insulin), the rate
      was increased by 0.2 mU x kg(-1) x min(-1), and from 120 to 240 min (High
      Insulin) insulin was infused at 1.5 mU x kg(-1) x min(-1). Insulin concentrations
      were significantly higher in NP than P during all periods. Matched subsets (n = 5
      NP and 6 P) were identified. In the subsets, insulin was 7 +/- 1, 9 +/- 1, and 28
      +/- 3 microU/ml (basal, Low Insulin, and High Insulin, respectively) in NP, and 5
      +/- 1, 7 +/- 1, and 27 +/- 3 microU/ml in P. Net hepatic glucose output was
      suppressed similarly in both subsets (> or =50% with Low Insulin, 100% with High
      Insulin), as was endogenous glucose rate of appearance. During High Insulin, NP
      dogs required more glucose (10.8 +/- 1.5 vs. 6.2 +/- 1.0 mg x kg(-1) x min(-1), P
      < 0.05), and hindlimb (primarily skeletal muscle) glucose uptake tended to be
      greater in NP than P (18.6 +/- 2.5 mg/min vs. 13.6 +/- 2.0 mg/min, P = 0.06). The
      normal canine liver remains insulin sensitive during late pregnancy. Differing
      insulin concentrations in pregnant and nonpregnant women and excessive insulin
      infusion rates may explain previous findings of hepatic insulin resistance in
      healthy pregnant women.

PMID- 16973937
TI  - Renovascular BK(Ca) channels are not activated in vivo under resting conditions
      and during agonist stimulation.
AB  - We investigated the role of large-conductance Ca(2+)-activated K(+) (BK(Ca))
      channels for the basal renal vascular tone in vivo. Furthermore, the possible
      buffering by BK(Ca) of the vasoconstriction elicited by angiotensin II (ANG II)
      or norepinephrine (NE) was investigated. The possible activation of renal
      vascular BK(Ca) channels by cAMP was investigated by infusing forskolin. Renal
      blood flow (RBF) was measured in vivo using electromagnetic flowmetry or
      ultrasonic Doppler. Renal preinfusion of tetraethylammonium (TEA; 3.0 mumol/min)
      caused a small reduction of baseline RBF, but iberiotoxin (IBT; 0.3 nmol/min) did
      not have any effect. Renal injection of ANG II (1-4 ng) or NE (10-40 ng) produced
      a transient decrease in RBF. These responses were not affected by preinfusion of
      TEA or IBT. Renal infusion of the BK(Ca) opener NS-1619 (90.0 nmol/min) did not
      affect basal RBF or the response to NE, but it attenuated the response to ANG II.
      Coadministration of NS-1619 with TEA or IBT abolished this effect. Forskolin
      caused renal vasodilation that was not inhibited by IBT. The presence of BK(Ca)
      channels in the preglomerular vessels was confirmed by immunohistochemistry.
      Despite their presence, there is no indication for a major role for BK(Ca)
      channels in the control of basal renal tone in vivo. Furthermore, BK(Ca) channels
      do not have a buffering effect on the rat renal vascular responses to ANG II and
      NE. The fact that NS-1619 attenuates the ANG II response indicates that the renal
      vascular BK(Ca) channels can be activated under certain conditions.

PMID- 16973938
TI  - Dexamethasone-induced protein degradation in cultured myotubes is p300/HAT
      dependent.
AB  - Muscle proteolysis during sepsis and other catabolic conditions is, at least in
      part, regulated by glucocorticoids. Dexamethasone-treated myotubes are a commonly
      used in vitro model of muscle wasting. We reported recently that treatment of
      cultured L6 myotubes with dexamethasone resulted in increased gene and protein
      expression of the nuclear cofactor p300 but it is not known whether
      glucocorticoids upregulate p300 histone acetyl transferase (HAT) activity in
      muscle and whether p300/HAT activity regulates glucocorticoid-induced muscle
      proteolysis. Here, we found that treatment of cultured L6 myotubes with
      dexamethasone resulted in increased nuclear p300/HAT activity. Treatment of
      myotubes with p300 siRNA or transfection of muscle cells with a plasmid
      expressing p300 that was mutated in its HAT activity domain blocked the
      dexamethasone-induced increase in protein degradation, supporting a role of
      p300/HAT in glucocorticoid-induced muscle proteolysis. In addition to increased
      HAT activity, treatment of the myotubes with dexamethasone resulted in reduced
      nuclear expression and activity of histone deacetylases (HDACs) 3 and 6. When
      myotubes were treated with the HDAC inhibitor trichostatin A, protein degradation
      increased to the same degree as in dexamethasone-treated myotubes. The results
      suggest that glucocorticoids increase HAT and decrease HDAC activities in muscle,
      changes that both favor hyperacetylation. The results also provide evidence that
      dexamethasone-induced protein degradation in cultured myotubes is, at least in
      part, regulated by p300/HAT activity.

PMID- 16973939
TI  - Regular heartbeat dynamics are associated with cardiac health.
AB  - The human heartbeat series is more variable and, hence, more complex in healthy
      subjects than in congestive heart failure (CHF) patients. However, little is
      known about the complexity of the heart rate variations on a beat-to-beat basis.
      We present an analysis based on symbolic dynamics that focuses on the dynamic
      features of such beat-to-beat variations on a small time scale. The sequence of
      acceleration and deceleration of eight successive heartbeats is represented by a
      binary sequence consisting of ones and zeros. The regularity of such binary
      patterns is quantified using approximate entropy (ApEn). Holter
      electrocardiograms from 30 healthy subjects, 15 patients with CHF, and their
      surrogate data were analyzed with respect to the regularity of such binary
      sequences. The results are compared with spectral analysis and ApEn of heart rate
      variability. Counterintuitively, healthy subjects show a large amount of regular
      beat-to-beat patterns in addition to a considerable amount of irregular patterns.
      CHF patients show a predominance of one regular beat-to-beat pattern (alternation
      of acceleration and deceleration), as well as some irregular patterns similar to
      the patterns observed in the surrogate data. In healthy subjects, regular beat-to
      beat patterns reflect the physiological adaptation to different activities, i.e.,
      sympathetic modulation, whereas irregular patterns may arise from parasympathetic
      modulation. The patterns observed in CHF patients indicate a largely reduced
      influence of the autonomic nervous system. In conclusion, analysis of short beat
      to-beat patterns with respect to regularity leads to a considerable increase of
      information compared with spectral analysis or ApEn of heart-rate variations.

PMID- 16973940
TI  - Combined prenatal and postnatal protein restriction influences adult kidney
      structure, function, and arterial pressure.
AB  - The effects of prenatal protein restriction on adult renal and cardiovascular
      function have been studied in considerable detail. However, little is known about
      the effects of life-long protein restriction, a common condition in the
      developing world. Therefore, we determined in rats the effects of combined pre-
      and postnatal protein restriction on adult arterial pressure and renal function
      and responses to increased dietary sodium. Nephron number was also determined.
      Male Sprague-Dawley rats were born to mothers fed a low [8% (wt/wt), LP] or
      normal [20% (wt/wt), NP] isocaloric protein diet throughout pregnancy and
      maintained on these diets after birth. At postnatal day 135, nephron number, mean
      arterial pressure (MAP), and renal function were determined. A high-NaCl [8.0%
      (wt/wt), high-salt] diet was fed to a subset of rats from weaning. MAP was less
      in LP than in NP rats (120 +/- 2 vs. 128 +/- 2 mmHg, P < 0.05) and was not
      significantly altered by increased salt intake. Nephron number was 31% less in LP
      than in NP rats (P < 0.001). The volume of individual glomeruli was also less in
      LP than in NP rats, as were calculated effective renal plasma flow and glomerular
      filtration rate. Glomerular filtration rate, but not effective renal plasma flow,
      appeared to be increased by high salt intake, particularly in LP rats. In
      conclusion, protein restriction induced a severe nephron deficit, but MAP was
      lower, rather than higher, in protein-restricted than in control rats in
      adulthood. These findings indicate that the postnatal environment plays a key
      role in determining the outcomes of developmental programming.

PMID- 16973942
TI  - Medication reconciliation implementation in an academic center.

PMID- 16973943
TI  - MA-SHARE MedsInfo-ED medication history pilot.

PMID- 16973944
TI  - Medication reconciliation.

PMID- 16973945
TI  - Medication reconciliation at Cambridge Health Alliance: experiences of a 3-campus
      health system in Massachusetts.

PMID- 16973946
TI  - An approach to medication reconciliation.

PMID- 16973947
TI  - Ambulatory care quality measures for the 6 aims from administrative data.
AB  - Pressure is building for performance measures that can be collected inexpensively
      and repeatedly for internal and external accountability and quality improvement.
      The objective of this study was to develop and test measures obtainable from
      administrative data covering each of the Institute of Medicine's (IOM) 6 aims.
      Measure definitions were developed for 3 common chronic conditions and were
      revised after testing the feasibility of collecting them from claims data. The
      setting was a large, multispecialty medical group in the Midwest and included all
      adult patients with diabetes, coronary heart disease, or depression. Problems
      identified in the original 99 measures led to refinements or elimination. The
      resulting 46 measures ready for use include 11 measures for 5 aims applicable to
      most common chronic conditions, plus 10 to 14 effectiveness measures for each
      condition. They have been successfully used to describe care quality changes for
      these patients over time. This starter set for the 6 IOM aims should be tested
      and expanded by others.

PMID- 16973948
TI  - An experiential interdisciplinary quality improvement education initiative.
AB  - Seven learners, including 2 preventive medicine fellows, 2 family medicine
      residents, 1 internal medicine resident, and 2 master's-level nursing students
      participated in an experiential 4-week quality improvement rotation at a major
      academic medical center. Together they worked on a quality improvement project
      that resulted in enhanced medication reconciliation in a preventive medicine
      clinic. Learner knowledge measured on the QI Knowledge Application Tool increased
      from an average of 2.33 before the start of the rotation to 3.43 (P = .043) by
      the end of the rotation. At the conclusion, all learners said they were confident
      or very confident that they could make a change to improve health care in a local
      setting. Although this pilot supports the feasibility and potential benefits of
      interdisciplinary quality improvement education, further research is necessary to
      explore strategies to implement the same on a larger scale, and to examine the
      impact on patient outcomes.

PMID- 16973949
TI  - Facilitators and barriers to 10 National Quality Forum safe practices.
AB  - The objective of this study was to identify facilitators and barriers to the
      implementation of 10 National Quality Forum (NQF) medication processes and the
      culture of safety practices in Georgia hospitals. In-depth interviews with
      hospital administrators were conducted to identify facilitators and barriers to
      the implementation of programs that support the NQF safe practices. Hospitals
      identified significant as well as other key factors that resulted in the adoption
      and/or nonadoption of medication and culture of safety practices. Informants also
      identified strategies used to overcome barriers that were experienced.
      Facilitators to both practices include administrative leadership support and
      education and training. The resistance to change was the most significant barrier
      identified in both the safe medication process interviews and the culture of
      safety interviews. Implementing safety practices can be a difficult process,
      replete with organizational, financial, and professional barriers. Strategies
      identified by our informants to overcome these barriers may assist other
      hospitals currently facing this challenge.

PMID- 16973950
TI  - Improving self-reporting of adverse drug events in a West Virginia hospital.
AB  - Adverse drug events significantly increase length of stay and costs of
      hospitalization but are underreported in health care institutions. We
      hypothesized that hospitals could improve the accuracy of adverse drug event self
      reporting by comparing adverse drug events recorded in an occurrence reporting
      tool with those detected by surveillance of "rescue" drugs administered to treat
      adverse drug events. We conducted a prospective cohort study of all adult
      inpatient discharges from a 200-bed rural acute care hospital in West Virginia
      during a 6-month period. We performed 3572 chart audits, of which 1011 included
      rescue drug administration. Our outcome measure was the proportion of adverse
      drug events in the rescue drug surveillance that were found in the occurrence
      reporting tool. We found that less than 4% of all adverse drug events involving
      use of rescue drugs were reported. We concluded that underreporting of
      preventable adverse drug events in this hospital is comparable to published rates
      and that surveillance of adverse drug events to detect underreporting is
      feasible.

PMID- 16973951
TI  - Consumer attitudes about health care-acquired infections and hand hygiene.
AB  - Mandatory reporting and disclosure of health care-acquired infections have
      resulted in controversy over the perceived notion that consumers will not
      understand how to interpret data and that such information may negatively
      influence utilization of hospitals. The objective was to determine consumers'
      attitudes about health care-acquired infections, hand hygiene practices, and
      patient empowerment. A telephone survey based on a random digit dialing sample of
      all households in the United States was conducted. Consumers were asked about
      choosing a hospital, hand hygiene practices, and health care-acquired infections.
      Some 94% of respondents rated environmental cleanliness as very important.
      Hospital infection rates would influence decision making for 93% of consumers.
      Four in 5 consumers said they would ask their health care worker to wash and
      sanitize his or her hands. Our findings strongly suggest that (1) consumers will
      use infection data in selecting and/or leaving a hospital system and (2)
      consumers are ready to be empowered with information to ensure a positive
      outcome.

PMID- 16973953
TI  - The intensive care unit, patient safety, and the Agency for Healthcare Research
      and Quality.

PMID- 16973956
TI  - Prolonged pancytopenia in a gene therapy patient with ADA-deficient SCID and
      trisomy 8 mosaicism: a case report.
AB  - A patient with adenosine deaminase-deficient severe combined immune deficiency
      (ADA-SCID) was enrolled in a study of retroviral-mediated ADA gene transfer to
      bone marrow hematopoietic stem cells. After the discontinuation of ADA enzyme
      replacement, busulfan (75 mg/m2) was administered for bone marrow cytoreduction,
      followed by infusion of autologous, gene-modified CD34+ cells. The expected
      myelosuppression developed after busulfan but then persisted, necessitating the
      administration of untransduced autologous bone marrow back-up at day 40. Because
      of sustained pancytopenia and negligible gene marking, diagnostic bone marrow
      biopsy and aspirate were performed at day 88. Analyses revealed hypocellular
      marrow and, unexpectedly, evidence of trisomy 8 in 21.6% of cells. Trisomy 8
      mosaicism (T8M) was subsequently diagnosed by retrospective analysis of a
      pretreatment marrow sample that might have caused the lack of hematopoietic
      reconstitution. The confounding effects of this preexisting marrow cytogenetic
      abnormality on the response to gene transfer highlights another challenge of gene
      therapy with the use of autologous hematopoietic stem cells.

PMID- 16973955
TI  - Hematologic manifestations of celiac disease.
AB  - Celiac disease is a common systemic disorder that can have multiple hematologic
      manifestations. Patients with celiac disease may present to hematologists for
      evaluation of various hematologic problems prior to receiving a diagnosis of
      celiac disease. Anemia secondary to malabsorption of iron, folic acid, and/or
      vitamin B12 is a common complication of celiac disease and many patients have
      anemia at the time of diagnosis. Celiac disease may also be associated with
      thrombocytosis, thrombocytopenia, leukopenia, venous thromboembolism,
      hyposplenism, and IgA deficiency. Patients with celiac disease are at increased
      risk of being diagnosed with lymphoma, especially of the T-cell type. The risk is
      highest for enteropathy-type T-cell lymphoma (ETL) and B-cell lymphoma of the
      gut, but extraintestinal lymphomas can also be seen. ETL is an aggressive disease
      with poor prognosis, but strict adherence to a gluten-free diet may prevent its
      occurrence.

PMID- 16973957
TI  - Expansion of Vdelta1 T lymphocytes producing IL-4 in low-grade non-Hodgkin
      lymphomas expressing UL-16-binding proteins.
AB  - Data on 23 patients with low-grade non-Hodgkin lymphomas (NHLs), 4 mantle (MT), 4
      marginal zone (MZ), and 15 follicular (FL), were analyzed and compared with 10
      high-risk (HR) B-cell chronic lymphocytic leukemias (B-CLLs) with lymph node
      involvement and 4 diffuse large-cell lymphomas (DLCLs). A significant increase in
      circulating Vdelta1 T lymphocytes producing interleukin-4 (IL-4) was found in
      patients with FL, MT, and MZ NHL, at variance with DLCL and HR B-CLL. IL-4 was
      also detectable in the sera and lymph nodes of the same patients. In 19 of the 23
      patients with NHL with increased circulating Vdelta1 T lymphocytes, B cells
      expressing the UL-16-binding proteins (ULBPs) ULBP2 or ULBP3 or both were found
      in peripheral blood, bone marrow, or lymph nodes. Of note, in HR B-CLL or in
      DLCL, where leukemic cells were negative for ULBPs, no Vdelta1 T-cell increase
      was found. Moreover, Vdelta1 T lymphocytes from patients with FL NHL proliferate
      in response to ULBP2+ and ULBP3+ lymphoma cells. Finally, patients with high
      expression of ULBPs, increased circulating Vdelta1 T lymphocytes, and high levels
      of serum IL-4 showed stable disease in a 1-year follow-up in contrast to patients
      with low circulating Vdelta1 T cells and undetectable IL-4 or ULBPs.

PMID- 16973958
TI  - BAFF and APRIL support chronic lymphocytic leukemia B-cell survival through
      activation of the canonical NF-kappaB pathway.
AB  - Chronic lymphocytic leukemia (CLL) B cells express BR3, the specific receptor for
      the B cell-activating factor of tumor necrosis factor family (BAFF). CLL cells
      also express 2 other receptors for BAFF, namely B-cell maturation antigen (BCMA)
      and the transmembrane activator and calcium modulator and cyclophilin ligand
      interactor (TACI), which also bind a proliferation-inducing ligand (APRIL). We
      found that signaling through BR3, but not BCMA or TACI, activated the alternative
      nuclear factor of kappa B (NF-kappaB) pathway in CLL cells, whereas signaling
      through BCMA/TACI induced activation of the canonical NF-kappaB pathway. Blocking
      BR3 did not inhibit the capacity of BAFF to support CLL cell survival in vitro.
      On the other hand, specifically blocking the canonical NF-kappaB pathway with
      UTC, an inhibitor of IkappaB kinase beta (IKKbeta), or transfection of CLL cells
      with the IkappaBalpha super-repressor, blocked the capacity of BAFF and APRIL to
      promote CLL cell survival in vitro. This contrasts what is found with normal
      blood B cells, which apparently depend on activation of the alternative NF-kappaB
      pathway for BAFF-enhanced survival. These findings suggest that inhibitors of
      protein kinase IKKbeta, which is required for activation of the canonical NF
      kappaB pathway, might have a therapeutic role in this disease.

PMID- 16973959
TI  - Innate immunity against vaccinia virus is mediated by TLR2 and requires TLR
      independent production of IFN-beta.
AB  - Vaccinia virus (VV) has been used extensively as a vaccine vehicle in the
      clinical application for infectious diseases and cancer. Previous studies have
      suggested that the unique potency of VV-based vaccine lies in its effective
      activation of the innate immune system. However, how VV activates innate immune
      pathways remains largely unknown. In this study, we showed that VV elicited
      innate immune response through both Toll-like receptor (TLR)-dependent and 
      independent pathways. The TLR pathway was mediated by TLR2 and MyD88, leading to
      the production of proinflammatory cytokines, whereas activation of the TLR
      independent pathway resulted in the secretion of IFN-beta. More importantly, both
      TLR-dependent and -independent pathways were required for activating innate and
      adaptive immunity to VV in vivo. These findings represent the first evidence that
      innate immune recognition of VV is mediated by TLR2, demonstrate that one
      pathogen can target both TLR and non-TLR innate immune pathways to work together
      in achieving efficient activation of host defense, and suggest potential new
      strategies for the design of effective vaccines.

PMID- 16973960
TI  - Regulation of dendritic-cell differentiation by bone marrow stroma via different
      Notch ligands.
AB  - Notch is a major factor mediating interaction between hematopoietic progenitor
      cells (HPCs) and bone marrow stroma (BMS). However its contribution to dendritic
      cell (DC) differentiation is controversial. We found that main Notch ligands
      Delta-1 and Jagged-1 had the opposite effect on DC differentiation. Delta-1
      promoted generation of fully differentiated DCs, whereas Jagged-1 stimulated
      accumulation of DC precursors but prevented their transition to terminally
      differentiated DCs. BMS expressed a substantially higher level of Jagged-1 than
      Delta-1. Just the opposite expression pattern was observed in spleen stroma (SS).
      The BMS effect on DC differentiation was similar to that of Jagged-1, whereas the
      effect of SS was similar to the effect of Delta-1. Down-regulation of Jagged-1 in
      BMS substantially increased DC differentiation. Experiments in vivo with adoptive
      transfer of DC precursors further supported the different roles of BMS and SS in
      DC development. Jagged-1 and Delta-1 equally activated CBF-1/RBPJkappa
      transcription factor, which is a major Notch target. However, they produced a
      different pattern of activation of Notch target gene Hes1. Overexpression of Hes1
      resulted in increased DC differentiation from HPCs. Thus, this study not only
      revealed the different role of Notch ligands in DC differentiation but also may
      provide a new insight into regulation of DC differentiation by BMS.

PMID- 16973961
TI  - Rce1 deficiency accelerates the development of K-RAS-induced myeloproliferative
      disease.
AB  - The RAS proteins undergo farnesylation of a carboxyl-terminal cysteine (the "C"
      of the carboxyl-terminal CaaX motif). After farnesylation, the 3 amino acids
      downstream from the farnesyl cysteine (the -aaX of the CaaX motif) are released
      by RAS-converting enzyme 1 (RCE1). We previously showed that inactivation of Rce1
      in mouse fibroblasts mislocalizes RAS proteins away from the plasma membrane and
      inhibits RAS transformation. Therefore, we hypothesized that the inactivation of
      Rce1 might inhibit RAS transformation in vivo. To test this hypothesis, we used
      Cre/loxP recombination techniques to simultaneously inactivate Rce1 and activate
      a latent oncogenic K-RAS allele in hematopoietic cells in mice. Normally,
      activation of the oncogenic K-RAS allele in hematopoietic cells leads to rapidly
      progressing and lethal myeloproliferative disease. Contrary to our hypothesis,
      the inactivation of Rce1 actually increased peripheral leukocytosis, increased
      the release of immature hematopoietic cells into the circulation and the
      infiltration of cells into liver and spleen, and caused mice to die more rapidly.
      Moreover, in the absence of Rce1, splenocytes and bone marrow cells expressing
      oncogenic K-RAS yielded more and larger colonies when grown in methylcellulose.
      We conclude that the inactivation of Rce1 worsens the myeloproliferative disease
      caused by oncogenic K-RAS.

PMID- 16973962
TI  - Chemokines CCL19 and CCL21 promote activation-induced cell death of antigen
      responding T cells.
AB  - Secondary lymphoid organs (SLOs) provide a niche for the initiation and
      regulation of T-cell responses, but the mechanisms have been poorly understood.
      We investigated the influence of chemokines CCL19 and CCL21 constitutively
      expressed in SLOs on activation-induced cell death (AICD) of CD4+ T cells. When
      paucity of lymph node T cells (plt) mutant mice lacking expression of CCL19/CCL21
      were primed with OVA/CFA, both expansion of OVA-responding CD4+ T cells in the
      draining lymph nodes and an in vitro recall response were prolonged as compared
      with responses in wild-type (WT) mice. The apoptotic cell frequency among OVA
      responding CD4+ T cells was similarly low in plt/plt and WT mice during the
      clonal expansion phase. However, during the clonal contraction phase, the
      frequency never increased in plt/plt mice, whereas in WT mice it continuously
      increased to a peak 18 days after immunization. The presence of CCL19/CCL21
      during the in vitro stimulation of CD4+ T cells with anti-CD3 plus anti-CD28
      significantly enhanced in vitro AICD induction of the restimulated T cells,
      partially through enhancing expression of Fas ligand. Our results suggest that
      CCL19/CCL21 produced by stromal cells and antigen-presenting cells regulate CD4+
      T-cell immune responses in SLOs by promoting AICD.

PMID- 16973963
TI  - Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia
      in complete molecular remission for more than 2 years.
AB  - In the present study, we address the issue of the discontinuation of imatinib
      mesylate (Gleevec) in chronic myelogenous leukemia with undetectable residual
      disease for more than 2 years. Twelve patients were included. The median duration
      of real-time quantitative-polymerase chain reaction (RTQ-PCR) negativity and
      imatinib therapy were, respectively, 32 months (range, 24-46 months) and 45
      months (range, 32-56 months) before imatinib interruption. Six patients displayed
      a molecular relapse with a detectable BCR-ABL transcript at 1, 1, 2, 3, 4, and 5
      months. Imatinib was then reintroduced and led to a novel molecular response in
      most patients. Six other patients (50%) still have an undetectable level of BCR
      ABL transcript after a median follow-up of 18 months (range, 9-24 months). We
      hypothesize that relapses observed within 6 months reflect the kinetics of
      undetectable dividing chronic myelogenous leukemia (CML) cells. Those cells may
      be eradicated or controlled in long-term nonrelapsing patients, as described in
      our study.

PMID- 16973964
TI  - Rapid quantification of naive alloreactive T cells by TNF-alpha production and
      correlation with allograft rejection in mice.
AB  - Allograft transplantation requires chronic immunosuppression, but there is no
      effective strategy to evaluate the long-term maintenance of immunosuppression
      other than assessment of graft function. The ability to monitor naive
      alloreactive T cells would provide an alternative guide for drug therapy at
      early, preclinical stages of graft rejection and for evaluating tolerance
      inducing protocols. To detect and quantify naive alloreactive T cells directly ex
      vivo, we used the unique ability of naive T cells to rapidly produce TNF-alpha
      but not IFN-gamma. Naive alloreactive T cells were identified by the production
      of TNF-alpha after a 5-hour in vitro stimulation with alloantigen and were
      distinguished from effector/memory alloreactive T cells by the inability to
      produce IFN-gamma. Moreover, naive alloreactive T cells were not detected in mice
      tolerized against specific alloantigens. The frequency of TNF-alpha-producing
      cells was predictive for rejection in an in vivo cytotoxicity assay and
      correlated with skin allograft rejection. Naive alloreactive T cells were also
      detected in humans, suggesting clinical relevance. We conclude that rapid
      production of TNF-alpha can be used to quantify naive alloreactive T cells, that
      it is abrogated after the induction of tolerance, and that it is a potential tool
      to predict allograft rejection.

PMID- 16973965
TI  - The actin cloud induced by LFA-1-mediated outside-in signals lowers the threshold
      for T-cell activation.
AB  - The dynamic rearrangement of the actin cytoskeleton plays critical roles in T
      cell receptor (TCR) signaling and immunological synapse (IS) formation in T
      cells. Following actin rearrangement in T cells upon TCR stimulation, we found a
      unique ring-shaped reorganization of actin called the "actin cloud," which was
      specifically induced by outside-in signals through lymphocyte function-associated
      antigen-1 (LFA-1) engagement. In T-cell-antigen-presenting cell (APC)
      interactions, the actin cloud is generated in the absence of antigen and
      localized at the center of the T-cell-APC interface, where it accumulates LFA-1
      and tyrosine-phosphorylated proteins. The LFA-1-induced actin cloud formation
      involves ADAP (adhesion- and degranulation-promoting adaptor protein)
      phosphorylation, LFA-1/ADAP assembly, and c-Jun N-terminal kinase (JNK)
      activation, and occurs independent of TCR and its proximal signaling. The
      formation of the actin cloud lowers the threshold for subsequent T-cell
      activation. Thus, the actin cloud induced by LFA-1 engagement may serve as a
      possible platform for LFA-1-mediated costimulatory function for T-cell
      activation.

PMID- 16973966
TI  - NPC1L1: evolution from pharmacological target to physiological sterol
      transporter.
AB  - Niemann-Pick C1-like 1 protein (NPC1L1) was recently shown to be the molecular
      target of the cholesterol absorption inhibitor class of drugs, of which ezetimibe
      is the first widely used member. Since its discovery, NPC1L1 has also been shown
      to play a focal physiological role in intestinal absorption of sterols, including
      plant sterols and cholesterol. Evidence in support of this new metabolic pathway
      has been garnered not only through human, animal, and cell studies of function
      but also through the use of human genetics as an approach to study the
      association of NPC1L1 sequence variation with metabolic and drug-response
      phenotypes. The example of NPC1L1 shows how the elucidation of a pharmacological
      target can serve as a means to gain understanding of a key physiological pathway.

PMID- 16973967
TI  - T cells in atherogenesis: for better or for worse?
AB  - The idea that atherosclerosis is an inflammatory disease is no longer
      controversial. Instead, much of the current research is now focused on
      understanding what drives this inflammation and how it is regulated. Adaptive
      immunity, in particular T cells, is highly involved in atherogenesis. It is well
      known that different subsets of T cells can drive or dampen inflammatory
      processes, but we still have much to learn about the regulation of this balance
      in the context of atherosclerosis. This review summarizes our knowledge of T
      cells in atherogenesis, their potential antigens, their contact-dependent
      activities, and their secretion of inflammatory and antiinflammatory mediators,
      aiming to illustrate how T cells can aggravate or attenuate this disease through
      cross-talk with other cells within or outside the atherosclerotic plaque.

PMID- 16973968
TI  - Negative regulation of VEGF-induced vascular leakage by blockade of angiotensin
      II type 1 receptor.
AB  - OBJECTIVE: Permeability of blood vessels is essential for tissue homeostasis.
      However, disorganized hyperpermeability leads to progression of diseases.
      Vascular endothelial growth factor-A (VEGF) is a key regulator for leakiness of
      blood vessels and it has been reported that VEGF-mediated hyperpermeability was
      suppressed by angiopoietin-1 (Ang1). We found that Angiotensin-converting enzyme
      (ACE) was downregulated in endothelial cells by Ang1. ACE converts angiotensin I
      to angiotensin II (AII). Here, we studied the relationship between VEGF and AII
      relative to vascular permeability. METHODS AND RESULTS: We showed that VEGF
      mediated vascular hyperpermeability was suppressed in mice given AII type 1
      receptor (AT1R) blocker (ARB); the effect was also seen in AT1R-deficient mice.
      In this system, we found that ARB inhibited VEGF-induced gap formation.
      Furthermore, we ascertained that angioedema induced by overexpression of VEGF
      decreased noticeably in ARB-treated ischemic mice. CONCLUSIONS: Because ARB
      suppressed VEGF-induced vascular hyperpermeability, we propose that ARB may be
      used to minimize the risk of edema in therapeutic angiogenesis using VEGF.

PMID- 16973969
TI  - Iron chelation inhibits NF-kappaB-mediated adhesion molecule expression by
      inhibiting p22(phox) protein expression and NADPH oxidase activity.
AB  - OBJECTIVE: Excess iron may increase oxidative stress and play a role in vascular
      inflammation and atherosclerosis. Here we determined whether the iron chelator,
      desferrioxamine (DFO), ameliorates oxidative stress and cellular adhesion
      molecule expression in a murine model of local inflammation. METHODS AND RESULTS:
      Dorsal air pouches were created in C57BL/6J mice by subcutaneous injection of
      air. DFO (100 mg/kg body weight) was injected into the air pouch once a day for
      two days followed immediately on the second day by lipopolysaccharide (LPS; 2.5
      mg/kg body weight). The animals were euthanized 24 hours later for analysis of
      oxidative stress markers and adhesion molecules in air pouch tissue. LPS
      treatment enhanced protein levels of p22(phox), a catalytic subunit of NADPH
      oxidase, and increased NADPH oxidase activity and levels of superoxide radicals
      and hydrogen peroxide. Furthermore, LPS activated NF-kappaB and increased
      expression of adhesion molecules. All of these inflammatory responses were
      strongly suppressed by DFO, but not iron-loaded DFO. CONCLUSIONS: Our data show
      that DFO inhibits LPS-induced, NADPH oxidase-mediated oxidative stress and,
      hence, NF-kappaB activation and adhesion molecule expression in a murine model of
      local inflammation. Iron chelation may be helpful in treating atherosclerotic
      vascular diseases by ameliorating oxidative stress and inflammation.

PMID- 16973970
TI  - Abdominal aortic aneurysm: pathogenesis and implications for management.
AB  - Abdominal aortic aneurysm (AAA) affects approximately 5% of elderly men and is
      responsible for a significant number of deaths in Western Countries. At present
      surgery by open or endovascular means is the only widely used therapy for this
      condition. In this review we examine the risk factors, serum, and genetic
      associations of AAA. Epidemiology studies suggest that smoking cessation and
      control of cholesterol and blood pressure should reduce the number of patients
      developing AAA. Natural history studies suggest that smoking cessation should
      reduce the rate of progression of AAA. Clear level 1 evidence for drug treatments
      of AAA are presently lacking; however, animal and human in vitro studies suggest
      that medication targeted at reducing inflammation and proteolysis are most likely
      to be beneficial, with limited data to support the use of statins, Angiotensin II
      inhibitors, and macrolides. Work has commenced in understanding which patients,
      identified by clinical, serum, and genotype, are more at risk of AAA progression
      and thus should be selected out for aggressive treatment. Well designed large
      multicenter randomized controlled trials are required to examine the medical
      treatment of AAA.

PMID- 16973971
TI  - Phospholipase A2-modified low-density lipoprotein activates the
      phosphatidylinositol 3-kinase-Akt pathway and increases cell survival in
      monocytic cells.
AB  - OBJECTIVE: Monocyte survival is an important determinant in the development of
      atherosclerotic lesions. We investigated the influence of phospholipase A2
      modified LDL (PLA-LDL), a pro-atherogenic factor, on activation of the pro
      survival kinase Akt and cell death in monocytic cells. METHODS AND RESULTS: PLA
      LDL induced robust phosphorylation and activation of Akt in THP1 cells. It also
      attenuated oxidative stress-induced cell death, an effect abolished by
      phosphatidylinositol 3-kinase (PI3K) inhibition. In addition, PLA-LDL increased
      survival of human monocytes. We noticed that lipid products derived from LDL
      phospholipolysis are mediators of PLA-LDL-induced Akt activation. Arachidonic
      acid, which is released on phospholipase treatment of LDL, induced Akt
      phosphorylation and increased cell survival, whereas lysophosphatidylcholine,
      another compound generated by LDL phospholipolysis, induced only transient Akt
      phosphorylation and was cytotoxic. CONCLUSIONS: Our data indicate that PLA-LDL
      induces activation of the PI3K-Akt pathway and promotes monocytic cell survival,
      which may contribute to the pro-atherogenic effects of phospholipase A2-modified
      LDL.

PMID- 16973972
TI  - Low-density lipoprotein modified by macrophage-derived lysosomal hydrolases
      induces expression and secretion of IL-8 via p38 MAPK and NF-kappaB by human
      monocyte-derived macrophages.
AB  - OBJECTIVE: Modified lipoproteins induce inflammatory reactions in the
      atherosclerotic arterial wall. We have previously found that macrophages in
      atherosclerotic lesions secrete lysosomal hydrolases that can modify low-density
      lipoprotein (LDL) in vitro to generate "hydrolase-modified LDL" (H-LDL). Here, we
      studied whether H-LDL exerts inflammatory effects on cultured human macrophages.
      METHODS AND RESULTS: Using cytokine cDNA arrays, we found that H-LDL induced
      expression of IL-8, but not of the anti-inflammatory cytokines IL-10 and
      transforming growth factor (TGF)-beta, in human monocyte-derived macrophages. H
      LDL induced rapid phosphorylation of the p38 mitogen-activated protein kinase
      (MAPK), nuclear translocation of 2 transcription factors, nuclear factor kappaB
      (NF-kappaB) and activator protein 1 (AP-1), and time-dependent secretion of IL-8
      from the macrophages. Inhibition of MAPKs and of transcription factors showed
      that p38 MAPK and NF-kappaB, but not ERK1/2, JNK, or AP-1, were crucial for the H
      LDL-induced IL-8 secretion from the macrophages. CONCLUSIONS: The results show
      that by activating p38 MAPK and NF-kappaB, macrophage hydrolases modify LDL into
      biologically active particles capable of triggering the secretion of IL-8 in
      macrophages. Thus, activated hydrolase-secreting macrophages in atherosclerotic
      lesions may sustain a proatherogenic extracellular environment by hydrolyzing LDL
      and triggering it to act in an autocrine or paracrine fashion to induce IL-8
      secretion by the plaque macrophages.

PMID- 16973973
TI  - A proinflammatory state is detectable in obese children and is accompanied by
      functional and morphological vascular changes.
AB  - BACKGROUND: Obesity is generally accepted as a risk factor for premature
      atherosclerosis. Subclinical inflammation as quantified by blood levels of C
      reactive protein (CRP) contributes to the development and progression of
      atherosclerosis. We hypothesized that inflammation in obese children is related
      to functional and early morphological vascular changes. METHODS AND RESULTS:
      Blood levels of high sensitivity (hs) CRP, hsIL-6, the soluble intercellular
      adhesion molecule1 (ICAM-1), vascular cell adhesion molecule (VCAM)-1, and E
      selectin were measured in 145 severely obese (body mass index [BMI], 32.2+/-5.8
      kg/m2) and 54 lean (BMI, 18.9+/-3.2 kg/m2) children 12+/-4 years old. Flow
      mediated dilation (FMD) of the brachial artery and carotid intima-media thickness
      (IMT) measured by high-resolution ultrasound as markers of early vascular changes
      were assessed in 92 (77 obese and 15 lean) and 59 (50 obese and 9 lean) children,
      respectively. Obese children had significantly higher levels of hsCRP, hsIL-6,
      and E-selectin than healthy controls (4.1+/-4.8 versus 0.9+/-1.5 mg/L, P<0.001
      for hsCRP; 1.99+/-1.30 versus 1.42+/-1.01 pg/mL, P=0.05 for hsIL-6; and 78+/-38
      versus 59+/-29 ng/mL, P=0.01 for E-selectin). There were no differences in the
      levels of ICAM-1 and VCAM-1 between groups. Obese children had lower peak FMD
      response (7.70+/-6.14 versus 11.06+/-3.07%, P=0.006) and increased IMT (0.37+/
      0.04 versus 0.34+/-0.03 mm, P=0.03) compared with controls. Morbidly obese
      children (n=14, BMI 44.1+/-3.9 kg/m2) had highest levels of hsCRP (8.7+/-0.7
      mg/L), hsIL-6 (3.32+/-1.1 pg/mL), and E-selectin (83+/-40 ng/mL). CONCLUSIONS: A
      proinflammatory state is detectable in obese children, which is accompanied by
      impaired vascular endothelial function and early structural changes of arteries,
      even in young subjects at risk. It remains to be determined whether high hsCRP in
      obese children predicts cardiovascular events.

PMID- 16973974
TI  - N(epsilon)-(carboxymethyl)lysine depositions in intramyocardial blood vessels in
      human and rat acute myocardial infarction: a predictor or reflection of
      infarction?
AB  - OBJECTIVE: Advanced glycation end products (AGEs), such as N(epsilon)
      (carboxymethyl)lysine (CML), are implicated in vascular disease. We previously
      reported increased CML accumulation in small intramyocardial blood vessels in
      diabetes patients. Diabetes patients have an increased risk for acute myocardial
      infarction (AMI). Here, we examined a putative relationship between CML and AMI.
      METHODS AND RESULTS: Heart tissue was stained for CML, myeloperoxidase, and E
      selectin in AMI patients (n=26), myocarditis patients (n=17), and control
      patients (n=15). In AMI patients, CML depositions were 3-fold increased compared
      with controls in the small intramyocardial blood vessels and predominantly
      colocalized with activated endothelium (E-selectin-positive) both in infarction
      and noninfarction areas. A trend of increased CML positivity of the intima of
      epicardial coronary arteries did not reach significance in AMI patients. In the
      rat heart AMI model, CML depositions were undetectable after 24 hours of
      reperfusion, but became clearly visible after 5 days of reperfusion. In line with
      an inflammatory contribution, human myocarditis was also accompanied by
      accumulation of CML on the endothelium of intramyocardial blood vessels.
      CONCLUSIONS: CML, present predominantly on activated endothelium in small
      intramyocardial blood vessels in patients with AMI, might reflect an increased
      risk for AMI rather than being a result of AMI.

PMID- 16973975
TI  - Matrix Gla protein is associated with risk factors for atherosclerosis but not
      with coronary artery calcification.
AB  - OBJECTIVE: Atherosclerotic coronary artery calcification (CAC) is associated with
      increased coronary heart disease (CHD) risk. Matrix Gla protein (MGP) is an
      inhibitor of calcification in vivo. However, little is known regarding the
      distribution of circulating MGP and its associations with CHD risk factors or
      with CAC in humans. METHODS AND RESULTS: Serum MGP concentrations were determined
      in 2 independent populations of men and women free of clinically apparent
      cardiovascular disease: study A, n=316, mean age 58 years, and study B, n=452,
      mean age 68 years. CAC was determined by computed tomography. Mean MGP
      concentrations were 98.4 and 198 ng/mL in men, and 97.4 and 201 ng/mL in women,
      in study A and study B, respectively. In both cohorts, MGP levels were higher
      with increasing age. In age-adjusted analyses, there was an association of
      circulating MGP with increasing Framingham CHD risk score (in study A, P=0.003 in
      men and P=0.016 in women, respectively; in study B, a nonsignificant increase in
      men and P=0.05 in women, respectively). Significant associations of circulating
      MGP with high-density lipoprotein and other individual CHD risk factors were also
      noted in both cohorts. There were no consistent associations between MGP and CAC
      after adjustment for CHD risk score in the 2 cohorts. CONCLUSIONS: MGP is
      associated with individual CHD risk factors and the Framingham CHD risk score in
      men and women free of clinically apparent CHD. The relation of MGP with CAC
      deserves further study in larger populations.

PMID- 16973976
TI  - Conjugated equine estrogen, esterified estrogen, prothrombotic variants, and the
      risk of venous thrombosis in postmenopausal women.
AB  - BACKGROUND: Joint exposure to oral conjugated equine estrogen (CEE) and
      prothrombotic genetic variants factor II G20210A or factor V G1601A (Leiden)
      increase venous thrombotic risk 6- to 16-fold in postmenopausal women. Esterified
      estrogen (EE), an alternative estrogenic compound, appears not to be associated
      with increased risk and nothing is known about the joint risk with prothrombotic
      genetic variants. METHODS AND RESULTS: We conducted a population-based, case
      control study among postmenopausal women within a health maintenance
      organization. Subjects included 328 cases who sustained a first venous thrombosis
      and 1591 controls. Current hormone use was defined using electronic pharmacy
      records and variants FII G20210A and FV Leiden were genotyped using blood
      samples. FII and FV Leiden variants were associated with 2.1-fold and 3.7-fold
      increases in venous thrombotic risk, respectively. Overall, CEE use was
      associated with a 2.5-fold increase in risk compared with no hormone use, whereas
      EE use was not associated with a statistically increased risk. Compared with no
      hormone use and no variant, joint exposure to CEE and either prothrombotic
      variant was associated with an odds ratio (OR) of 9.1 (95% CI: 4.5 to 18.2),
      whereas joint exposure to EE and either variant was associated with an OR of 2.1
      (0.6 to 6.8). When analyses were restricted to hormone users with either variant,
      CEE use was associated with an OR of 5.3 (1.3 to 21.7) compared with EE use.
      CONCLUSIONS: These findings need replication and suggest EE use is associated
      with less risk than CEE use especially among 5% to 10% of women who are carriers
      of a prothrombotic variant.

PMID- 16973977
TI  - Physician-attributable differences in intensive care unit costs: a single-center
      study.
AB  - RATIONALE: Variation in practice and outcomes, not explained by patient or
      illness characteristics, is common in health care, including in intensive care
      units (ICUs). OBJECTIVE: To quantify within-ICU, between-physician variation in
      resource use in a single medical ICU. METHODS: This was a prospective,
      noninterventional study in a medical ICU where nine intensivists provide care in
      14-d rotations. Consecutive sample consisted of 1,184 initial patient admissions
      whose care was provided by a single intensivist. Multivariate models were
      constructed for average daily discretionary costs, ICU length of stay, and
      hospital mortality, adjusting for patient and illness characteristics, and
      workload. MEASUREMENTS AND MAIN RESULTS: The identity of the intensivist was a
      significant predictor for average daily discretionary costs (p < 0.0001), but not
      ICU length of stay (p = 0.33) or hospital mortality (p = 0.83). The intensivists
      had more influence on costs than all other variables except the severity and type
      of acute illness. Average daily discretionary costs varied by 43% across the
      different intensivists, equating to a mean difference of 1,003 dollars per
      admission between the highest and lowest terciles of intensivists. CONCLUSIONS:
      There are large differences among intensivists in the amount of resources they
      use to manage critically ill patients. Higher resource use was not associated
      with lower length of stay or mortality.

PMID- 16973979
TI  - Diagnosis of adrenal insufficiency in severe sepsis and septic shock.
AB  - RATIONALE: Diagnosis of adrenal insufficiency in critically ill patients has
      relied on random or cosyntropin-stimulated cortisol levels, and has not been
      corroborated by a more accurate diagnostic standard. OBJECTIVE: We used the
      overnight metyrapone stimulation test to investigate the diagnostic value of the
      standard cosyntropin stimulation test, and the prevalence of sepsis-associated
      adrenal insufficiency. METHODS: This was an inception cohort study. MEASUREMENTS
      AND RESULTS: In two consecutive septic cohorts (n = 61 and n = 40), in 44
      patients without sepsis and in 32 healthy volunteers, we measured (1) serum
      cortisol before and after cosyntropin stimulation, albumin, and corticosteroid
      binding globulin levels, and (2) serum corticotropin, cortisol, and 11beta
      deoxycortisol levels before and after an overnight metyrapone stimulation.
      Adrenal insufficiency was defined by postmetyrapone serum 11beta-deoxycortisol
      levels below 7 microg/dl. More patients with sepsis (31/61 [59% of original
      cohort with sepsis] and 24/40 [60% of validation cohort with sepsis]) met
      criteria for adrenal insufficiency than patients without sepsis (3/44; 7%) (p <
      0.001 for both comparisons). Baseline cortisol (< 10 microg/dl), Delta cortisol
      (< 9 microg/dl), and free cortisol (< 2 microg/dl) had a positive likelihood
      ratio equal to infinity, 8.46 (95% confidence interval, 1.19-60.25), and 9.50
      (95% confidence interval, 1.05-9.54), respectively. The best predictor of adrenal
      insufficiency (as defined by metyrapone testing) was baseline cortisol of 10
      microg/dl or less or Delta cortisol of less than 9 microg/dl. The best predictors
      of normal adrenal response were cosyntropin-stimulated cortisol of 44 microg/dl
      or greater and Delta cortisol of 16.8 microg/dl or greater. CONCLUSIONS: In
      sepsis, adrenal insufficiency is likely when baseline cortisol levels are less
      than 10 microg/dl or delta cortisol is less than 9 microg/dl, and unlikely when
      cosyntropin-stimulated cortisol level is 44 microg/dl or greater or Delta
      cortisol is 16.8 microg/dl or greater.

PMID- 16973980
TI  - Elevated exhaled nitric oxide in newborns of atopic mothers precedes respiratory
      symptoms.
AB  - RATIONALE: Exhaled nitric oxide (NO) is a well-known marker of established airway
      inflammation in asthma. Its role in the disease process before the onset of
      respiratory symptoms remains unclear. OBJECTIVES: To examine whether elevated NO
      in newborns with clinically naive airways is associated with subsequent
      respiratory symptoms in infancy. METHODS: We measured exhaled NO concentration
      and output after birth and prospectively assessed respiratory symptoms during
      infancy in a birth cohort of 164 unselected healthy neonates. We examined a
      possible association between NO and respiratory symptoms using Poisson regression
      analysis. RESULTS: In infants of atopic mothers, elevated NO levels after birth
      were associated with increased risk of subsequent respiratory symptoms (risk
      ratio [RR], 7.5; 95% confidence interval [CI], 1.7-32.4 for each nl/s increase in
      NO output; p = 0.007). Similarly, a positive association between NO and symptoms
      was seen in infants of smoking mothers (RR, 6.6; 95% CI, 2.3-19.3; p = 0.001),
      with the strongest association in infants whose mothers had both risk factors
      (RR, 21.8; 95% CI, 5.8-81.3; p < 0.001). CONCLUSIONS: The interaction of NO with
      maternal atopy and smoking on subsequent respiratory symptoms is present early in
      life. Clinically, noninvasive NO measurements in newborns may prove useful as a
      new means to identify high-risk infants. Future confirmation of a role for NO
      metabolism in the evolution of respiratory disease may provide an avenue for
      preventative strategies.

PMID- 16973978
TI  - Modulatory role for retinoid-related orphan receptor alpha in allergen-induced
      lung inflammation.
AB  - RATIONALE: Nuclear receptors play a critical role in the regulation of
      inflammation, thus representing attractive targets for the treatment of asthma.
      OBJECTIVE: In this study, we assess the potential regulatory function of retinoid
      related orphan receptor alpha (RORalpha) in the adaptive immune response using
      ovalbumin (OVA)-induced airway inflammation as a model. METHODS: Allergen-induced
      inflammation was compared between wild-type (WT) and staggerer (RORalpha(sg/sg))
      mice, a natural mutant strain that is deficient in RORalpha expression.
      MEASUREMENTS AND MAIN RESULTS: Despite robust increases in OVA-specific IgE,
      RORalpha(sg/sg) mice developed significantly less pulmonary inflammation, mucous
      cell hyperplasia, and eosinophilia compared with similarly treated WT animals.
      Induction of Th2 cytokines, including interleukin (IL)-4, IL-5, and IL-13, was
      also significantly less in RORalpha(sg/sg) mice. Microarray analysis using lung
      RNA showed increased expression of many genes, previously implicated in
      inflammation, in OVA-treated WT mice. These include mucin Muc5b, the chloride
      channel calcium-activated 3 (Clca3), macrophage inflammatory protein (MIP) 1alpha
      and 1beta, eotaxin-2, serum amyloid A3 (Saa3), and insulin-like growth factor 1
      (Igf1). These genes were induced to a greater extent in OVA-treated WT mice
      relative to RORalpha(sg/sg) mice. CONCLUSIONS: Our study demonstrates that mice
      deficient in RORalpha exhibit an attenuated allergic inflammatory response,
      indicating that RORalpha plays a critical role in the development of Th2-driven
      allergic lung inflammation in mice, and suggests that this nuclear receptor
      should be further evaluated as a potential asthma target.

PMID- 16973981
TI  - Ampakines alleviate respiratory depression in rats.
AB  - RATIONALE: There is a need for improved therapeutic interventions to treat both
      drug- and sleep-induced respiratory depression. Increased understanding of the
      neurochemical control of respiration will help identify a basis for advances.
      Activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
      type glutamate receptors positively modulates respiratory drive and
      rhythmogenesis in several brain regions including the pre-Botzinger complex.
      Ampakines are a diverse group of small molecules that activate subsets of these
      receptors. OBJECTIVE: We determined whether the ampakine CX546 would enhance
      respiratory drive and rhythmogenesis across various stages of development and
      whether this ampakine could counter opioid- and barbiturate-induced respiratory
      depression. METHODS: Respiratory frequency and amplitude were measured in the
      following rat models: (1) perinatal in vitro brainstem-spinal cord, (2) neonatal
      in vitro medullary slice, (3) juvenile in situ perfused, working heart-brainstem
      preparation, and (4) newborn and adult in vivo. RESULTS: Administration of CX546
      stimulated baseline respiratory frequency in perinatal in vitro preparations but
      not in older animals (greater than Postnatal Day 0). Furthermore, pharmacologic
      depression of respiratory frequency and amplitude was countered at all ages
      studied by the administration of CX546 in vitro, in situ, and in vivo.
      Significantly, CX546 countered opioid-induced breathing depression in all
      preparations, without altering analgesia as assessed by measuring the time to
      foot withdrawal in response to a thermal stimulus. CONCLUSIONS: CX546 effectively
      reverses opioid- and barbiturate-induced respiratory depression without reversing
      the analgesic response. These studies suggest that ampakines may be useful in
      preventing or reversing opioid-induced respiratory depression and identify the
      potential of ampakines for alleviating other forms of respiratory depression
      including sedative use and sleep apnea.

PMID- 16973982
TI  - Undiagnosed tuberculosis in a community with high HIV prevalence: implications
      for tuberculosis control.
AB  - BACKGROUND: Although failure of tuberculosis (TB) control in sub-Saharan Africa
      is attributed to the HIV epidemic, it is unclear why the directly observed
      therapy short-course (DOTS) strategy is insufficient in this setting. We
      conducted a cross-sectional survey of pulmonary TB (PTB) and HIV infection in a
      community of 13,000 with high HIV prevalence and high TB notification rate and a
      well-functioning DOTS TB control program. METHODS: Active case finding for PTB
      was performed in 762 adults using sputum microscopy and Mycobacterium
      tuberculosis culture, testing for HIV, and a symptom and risk factor
      questionnaire. Survey findings were correlated with notification data extracted
      from the TB treatment register. RESULTS: Of those surveyed, 174 (23%) tested HIV
      positive, 11 (7 HIV positive) were receiving TB therapy, 6 (5 HIV positive) had
      previously undiagnosed smear-positive PTB, and 6 (4 HIV positive) had smear
      negative/culture-positive PTB. Symptoms were not a useful screen for PTB. Among
      HIV-positive and -negative individuals, prevalence of notified smear-positive PTB
      was 1,563/100,000 and 352/100,000, undiagnosed smear-positive PTB prevalence was
      2,837/100,000 and 175/100,000, and case-finding proportions were 37 and 67%,
      respectively. Estimated duration of infectiousness was similar for HIV-positive
      and HIV-negative individuals. However, 87% of total person-years of undiagnosed
      smear-positive TB in the community were among HIV-infected individuals.
      CONCLUSIONS: PTB was identified in 9% of HIV-infected individuals, with 5% being
      previously undiagnosed. Lack of symptoms suggestive of PTB may contribute to low
      case-finding rates. DOTS strategy based on passive case finding should be
      supplemented by active case finding targeting HIV-infected individuals.

PMID- 16973984
TI  - Ancestry-environment interactions and asthma risk among Puerto Ricans.
AB  - BACKGROUND: Puerto Ricans, an admixed population of African, European, and Native
      American ancestries, have the highest asthma prevalence, morbidity, and mortality
      rates of any United States' population. Although socioeconomic status (SES) is
      negatively correlated with asthma incidence in most populations, no such
      relationship has been identified among Puerto Ricans. We hypothesized that, in
      this admixed population, the association between SES and asthma may interact with
      genetic ancestry. METHODS: We analyzed 135 Puerto Rican subjects with asthma and
      156 control subjects recruited from six different recruitment centers in Puerto
      Rico. Individual ancestry for each subject was estimated using 44 ancestry
      informative markers. SES was assigned using the census tracts' median family
      income. Analyses of SES were based on the SES of the clinic site from which the
      subjects were recruited and on a subset of individuals on whom home address-based
      SES was available. RESULTS: In the two (independent) analyses, we found a
      significant interaction between SES, ancestry, and asthma disease status. At
      lower SES, European ancestry was associated with increased risk of asthma,
      whereas African ancestry was associated with decreased risk. The opposite was
      true for their higher SES counterparts. CONCLUSIONS: The observed interaction may
      help to explain the unique pattern of risk for asthma in Puerto Ricans and the
      lack of association with SES observed in previous studies when not accounting for
      varying proportions of ancestry.

PMID- 16973983
TI  - Regular smoking and asthma incidence in adolescents.
AB  - RATIONALE: Although involuntary exposure to maternal smoking during the in utero
      period and to secondhand smoke are associated with occurrence of childhood
      asthma, few studies have investigated the role of active cigarette smoking on
      asthma onset during adolescence. OBJECTIVES: To determine whether regular smoking
      is associated with the new onset of asthma during adolescence. METHODS: We
      conducted a prospective cohort study among 2,609 children with no lifetime
      history of asthma or wheezing who were recruited from fourth- and seventh-grade
      classrooms and followed annually in schools in 12 southern California
      communities. Regular smoking was defined as smoking at least seven cigarettes per
      day on average over the week before and 300 cigarettes in the year before each
      annual interview. Incident asthma was defined using new cases of physician
      diagnosed asthma. MEASUREMENTS AND MAIN RESULTS: Regular smoking was associated
      with increased risk of new-onset asthma. Children who reported smoking 300 or
      more cigarettes per year had a relative risk (RR) of 3.9 (95% confidence interval
      [95% CI], 1.7-8.5) for new-onset asthma compared with nonsmokers. The increased
      risk from regular smoking was greater in nonallergic than in allergic children.
      Regular smokers who were exposed to maternal smoking during gestation had the
      largest risk from active smoking (RR, 8.8; 95% CI, 3.2-24.0). CONCLUSIONS:
      Regular smoking increased risk for asthma among adolescents, especially for
      nonallergic adolescents and those exposed to maternal smoking during the in utero
      period.

PMID- 16973985
TI  - Airway eosinophilia in children with severe asthma: predictive values of
      noninvasive tests.
AB  - RATIONALE: Children with severe asthma experience persistent symptoms despite
      maximal conventional treatment. Fraction of exhaled nitric oxide (Fe(NO)) and
      sputum eosinophils are used as markers of airway inflammation to guide treatment
      with steroids, but no data are available on how reliable they are in predicting
      airway eosinophilia assessed bronchoscopically in these children. OBJECTIVES: To
      determine how Fe(NO) and sputum eosinophils predict airway eosinophilia measured
      in both bronchoalveolar lavage (BAL) and endobronchial biopsy. METHODS: Twenty
      seven children with moderate to severe persistent asthma attempted measurement of
      Fe(NO) and sputum eosinophils, followed by bronchoscopy, BAL, and endobronchial
      biopsy within 24 h. MAIN RESULTS: Significant correlations were found between
      eosinophils in sputum and both BAL eosinophils (n = 20, r = 0.45, p = 0.045) and
      Fe(NO) (n = 23, r = 0.42, p = 0.049). The relationship between Fe(NO) and BAL
      eosinophils was also significant with a stronger correlation (n = 24, r = 0.54, p
      = 0.006). The positive predictive value (PPV) for increased sputum eosinophil
      percentage (> 2.5%) to detect elevated eosinophils in BAL (> 1.19%) was 75%; the
      negative predictive value (NPV) was 63%. All patients with both increased sputum
      eosinophils and an elevated Fe(NO) value (> 23 ppb) had elevated eosinophils in
      BAL (PPV, 100%); the NPV of these two markers was 65%. Eight of nine patients
      without any sputum eosinophils had normal subepithelial eosinophil numbers (<
      1.2%; NPV, 89%). However, the PPV of any sputum eosinophils for increased
      subepithelial eosinophilia was only 36.4%. CONCLUSIONS: There was moderate
      agreement between both Fe(NO) and sputum eosinophils and BAL eosinophils. There
      was good NPV, but only poor PPV for these markers for mucosal eosinophilia.

PMID- 16973986
TI  - Development and validation of a clinical prediction rule for severe community
      acquired pneumonia.
AB  - RATIONALE: Objective strategies are needed to improve the diagnosis of severe
      community-acquired pneumonia in the emergency department setting. OBJECTIVES: To
      develop and validate a clinical prediction rule for identifying patients with
      severe community-acquired pneumonia, comparing it with other prognostic rules.
      METHODS: Data collected from clinical information and physical examination of
      1,057 patients visiting the emergency department of a hospital were used to
      derive a clinical prediction rule, which was then validated in two different
      populations: 719 patients from the same center and 1,121 patients from four other
      hospitals. MEASUREMENTS AND MAIN RESULTS: In the multivariate analyses, eight
      independent predictive factors were correlated with severe community-acquired
      pneumonia: arterial pH < 7.30, systolic blood pressure < 90 mm Hg, respiratory
      rate > 30 breaths/min, altered mental status, blood urea nitrogen > 30 mg/dl,
      oxygen arterial pressure < 54 mm Hg or ratio of arterial oxygen tension to
      fraction of inspired oxygen < 250 mm Hg, age > or = 80 yr, and
      multilobar/bilateral lung affectation. From the beta parameter obtained in the
      multivariate model, a score was assigned to each predictive variable. The model
      shows an area under the curve of 0.92. This rule proved better at identifying
      patients evolving toward severe community-acquired pneumonia than either the
      modified American Thoracic Society rule, the British Thoracic Society's CURB-65,
      or the Pneumonia Severity Index. CONCLUSIONS: A simple score using clinical data
      available at the time of the emergency department visit provides a practical
      diagnostic decision aid, and predicts the development of severe community
      acquired pneumonia.

PMID- 16973988
TI  - Extensively drug resistant tuberculosis.

PMID- 16973987
TI  - Combination therapy with a long-acting beta-agonist and a leukotriene antagonist
      in moderate asthma.
AB  - RATIONALE: Long-acting beta-agonists (LABAs) and inhaled corticosteroids
      administered together appear to be complementary in terms of effects on asthma
      control. The elements of asthma control achieved by LABAs (improved lung
      function) and leukotriene receptor antagonists (LTRAs; protection against
      exacerbations) may be complementary as well. OBJECTIVE: We sought to determine
      whether the combination of the LTRA montelukast and the LABA salmeterol could
      provide an effective therapeutic strategy for asthma. METHODS AND MEASUREMENTS:
      In a randomized, placebo-controlled, crossover study of 192 subjects with
      moderate asthma, we compared the clinical efficacy of regular treatment over 14
      weeks with the combination of montelukast and salmeterol to that with the
      combination of beclomethasone and salmeterol in moderate asthma. The primary
      efficacy outcome was time to treatment failure. MAIN RESULTS: Three months after
      the randomization of the last subject, the Data and Safety Monitoring Board
      determined that the primary research question had been answered and terminated
      the trial. The combination of montelukast and salmeterol was inferior to the
      combination of beclomethasone and salmeterol as judged by protection against
      asthma treatment failures (p = 0.0008), lung function (26 L/min difference in
      a.m. peak expiratory flow rate, p = 0.011), asthma control score (0.22 difference
      in Asthma Control Questionnaire score, p = 0.038), and markers of inflammation
      and airway reactivity. CONCLUSIONS: Patients with moderate asthma similar to
      those we studied should not substitute the combination of an LTRA and an LABA for
      the combination of inhaled corticosteroid and an LABA.

PMID- 16973989
TI  - Emergency contraception.

PMID- 16973990
TI  - Salt reduction in the United States.

PMID- 16973991
TI  - Non-cephalic presentation in late pregnancy.

PMID- 16973992
TI  - Size of the needle for infant vaccination.

PMID- 16973994
TI  - Disabled people face difficulties in accessing primary care.

PMID- 16973995
TI  - Experts devise strategy to fight new TB strain.

PMID- 16973996
TI  - Nicotine content in smoke from US cigarettes has increased.

PMID- 16974002
TI  - Doctors question India's polio strategy after surge in number of cases.

PMID- 16974003
TI  - Statin prescribing fell after drug became available over the counter.

PMID- 16974006
TI  - Israel permits ova donation from woman who is not undergoing treatment.

PMID- 16974011
TI  - In the eye of the storm.

PMID- 16974012
TI  - Diagnosis and management of ankylosing spondylitis.

PMID- 16974013
TI  - Glycated haemoglobin (HbA1c) monitoring.

PMID- 16974014
TI  - A life threatening complication after ingestion of sodium phosphate bowel
      preparation.

PMID- 16974016
TI  - Role of systematic reviews in detecting plagiarism: case of Asim Kurjak.

PMID- 16974017
TI  - Ethical writing should be taught.

PMID- 16974018
TI  - The case of the misleading funnel plot.

PMID- 16974019
TI  - Preventing and detecting early vascular effects of diabetes: improvement must
      continue or costs will escalate.

PMID- 16974021
TI  - A prescription for better prescribing: medical education is a continuum.

PMID- 16974022
TI  - Role of cholinesterase inhibitors in dementia care: memory clinics and
      cholinesterase inhibitors have their place.

PMID- 16974023
TI  - Rare diseases need a generic approach.

PMID- 16974024
TI  - Preventing and detecting early vascular effects of diabetes: word of caution on
      peripheral arterial assessment.

PMID- 16974025
TI  - Avoiding deaths on Everest.

PMID- 16974026
TI  - Cuba's international cooperative efforts in health.

PMID- 16974027
TI  - Role of cholinesterase inhibitors in dementia care: NICE's economic analysis has
      limitations.

PMID- 16974028
TI  - Capsule enteroscopy in India: early steps.

PMID- 16974029
TI  - Susceptibility of lactase to luminal proteases in developing rat intestine.
AB  - BACKGROUND: Postnatal development of rat intestine is associated with a decline
      in brush-border lactase activity. This phenomenon is similar to the adulthood
      hypolactasia in humans. However, the mechanism underlying this process is not
      understood. METHODS: The effect of luminal proteases from adult rat intestine on
      the intestinal lactase activity in animals aged 7, 14, 21 and 30 days was studied
      in in vitro experiments. Lactase levels were estimated using enzyme assays and
      Western blot analysis. RESULTS: Incubation of purified brush borders with
      increasing concentrations of luminal proteases reduced the lactase activity in
      intestine of 7-day-old rats, but not in that of adult animals. Western blot
      analysis revealed low signal of the 220-kDa lactase protein in 7-day-old animals,
      but not that of older weaned animals. CONCLUSIONS: Our findings suggest that
      luminal proteases may be responsible for the maturational decline in intestinal
      lactase activity.

PMID- 16974030
TI  - Glycogen storage disease: report of 17 cases from southern India.
AB  - BACKGROUND: There are only four reports of glycogen storage disease (GSD),
      totalling six cases, from India. OBJECTIVE: To determine the clinical phenotypes
      of children diagnosed with GSD in southern India. METHODS: Liver biopsy reports
      from 1994 to 2005 were reviewed and GSD was confirmed in 17 patients. All 17
      patients were tested for the three commonest GSD 1a mutations by restriction
      fragment length polymorphism: R83C, Q347X and G727T. RESULTS: They presented at
      mean age of 15 months (range, birth to 46 months) with hypoglycemia, hepatomegaly
      and delayed milestones. None of the patients showed R83C, Q347X or G727T
      mutation. CONCLUSION: Glycogen storage disease may not be rare in India. The
      commonest 1a mutations are probably rare here.

PMID- 16974031
TI  - Airway resistance in irritable bowel syndrome as measured by impulse
      oscillometry.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is associated with bronchial asthma.
      However, published data on airway resistance or impedance in patients with IBS
      but without any respiratory symptoms are lacking. METHODS: Patients with IBS but
      no respiratory symptoms underwent spirometry and airway resistance measurement
      using impulse oscillometry; the data were compared with those from 97 historical
      age- and sex-matched healthy control subjects. RESULTS: Patients had lower FEV1
      (3.03 [0.74] vs. 3.35 [0.80] L/min; p=0.004) and FVC (3.56 [0.85] vs. 3.88 [0.9];
      p=0.01) than healthy subjects; however, the values were within the normal range.
      Patients had a higher resistance at 5 Hz (0.45 [0.42] vs. 0.30 [0.15] kPa L/s;
      p=0.003); however, reactance at this frequency was not significantly different (
      0.08 [0.30] vs. -0.10 [0.09] kPa L/s; p=0.438). CONCLUSION: Patients with IBS
      have increased airway resistance as compared to healthy subjects, as measured by
      impulse oscillometry; however, reactance is unchanged, indicating no change in
      elastic resistance.

PMID- 16974032
TI  - Degos' disease: acute abdomen with skin rash.

PMID- 16974034
TI  - Alpha-1 antitrypsin deficiency among Indian children with liver disorders.
AB  - AIMS: To determine the frequency of alpha-1 antitrypsin (AAT) deficiency in
      children with chronic liver disease (CLD) and neonatal cholestasis syndrome
      (NCS). METHODS: All children with NCS (n=23) or CLD (n=35) attending the
      Pediatric Gastroenterology Clinic between November 2003 and July 2005 were
      screened for AAT deficiency using phenotyping through isoelectric focusing of
      plasma. RESULTS: Of the 58 children studied, 57 had normal PiMM phenotype. One
      child with CLD had the M1E type of normal variant. None of the patients had the
      abnormal phenotype PiZZ. CONCLUSION: AAT deficiency is infrequent among children
      with CLD and NCS in our region.

PMID- 16974033
TI  - Capsule endoscopy in obscure gastrointestinal bleeding--an Indian experience.
AB  - BACKGROUND: Obscure gastrointestinal bleeding (OGIB) is a common indication for
      capsule endoscopy (CE). Reports on diagnostic yield of CE in this situation show
      a wide variation. We evaluated the diagnostic yield and clinical impact of CE in
      patients with OGIB. METHODS: We reviewed the medical records of patients with
      OGIB who underwent CE at our institution between June 2002 and October 2005.
      RESULTS: 154 patients (mean age 47 [SD 17] years; 117 men), including 74 with
      overt OGIB and 80 with occult OGIB, underwent CE. CE yielded positive findings in
      57 of 74 patients (77%) with overt OGIB and 22 of 80 (27%) of those with occult
      OGIB (p < 0.0001); the overall positive diagnostic yield was 52%. NSAID-induced
      lesions (15%), angiodysplasias (14%) and aphthous ulcers (12%) were the most
      frequent findings. CE helped in planning further management in 79% of patients
      with overt OGIB and 26% of those with occult OGIB. CONCLUSION: CE is a useful
      diagnostic technique in patients with OGIB, especially those with overt OGIB.

PMID- 16974035
TI  - Long-standing diarrhea in thalassemia major.

PMID- 16974036
TI  - Treatment of post-cholecystectomy bile duct strictures--push or sidestep?
AB  - Management of post-cholecystectomy bile duct strictures can be complex.
      Traditional treatment has been surgical reconstruction. In recent years
      endoscopic stenting has been successful in a selected subgroup of patients with
      iatrogenic bile duct strictures. Adequate information about long-term results of
      endoscopic stenting as definite treatment for such strictures is still awaited.
      Surgery is a reliable and time-tested method and results of numerous studies show
      its long-term success in relieving biliary obstruction with minimal morbidity.

PMID- 16974037
TI  - Benign biliary stricture--should they be dilated or treated surgically?
AB  - Management of benign biliary stricture remains a challenge for both surgeons and
      therapeutic endoscopists. Traditionally, surgery is considered the mainstay of
      treatment, but it is associated with significant morbidity and variable long-term
      outcome. With advances in endoscopic techniques and accessories, endoscopic
      management is emerging as an effective option. Outcome of endoscopic management
      depends on both the etiology and location of stricture. Current data suggest that
      long-term results with multiple plastic stents are superior to those with single
      plastic stent. Removable covered metal stents are a good alternative. The role of
      bio-absorbable self-expanding stents needs to be evaluated further.

PMID- 16974038
TI  - Polyp within gastric diverticulum.

PMID- 16974040
TI  - Acute abdomen due to eosinophilic colitis with liver abscess.
AB  - Eosinophilic colitis is an uncommon condition and rarely presents as acute
      abdomen. We report a 65-year-old man who presented with acute abdomen-- severe
      pain in upper abdomen, with pyrexia, tachycardia, guarding and right-sided
      intercostal tenderness--secondary to eosinophilic colitis and was successfully
      managed. He had additional problems in form of cirrhosis, chronic hepatitis,
      cholangitis, pyogenic liver abscesses and gout.

PMID- 16974039
TI  - Distinguishing between periampullary carcinoids and carcinomas--is this possible
      preoperatively?
AB  - It is difficult to distinguish between carcinoid tumors of the pancreatic head
      and periampullary region and carcinomas preoperatively. Between 1996 and 2002,
      125 consecutive pancreaticoduodenectomies done by us for periampullary tumors (14
      carcinoids, 111 carcinomas) were analyzed. Patients with carcinoid tumors had
      significantly younger mean age (48 vs. 54 years), longer history (32 vs. 8
      weeks), lower serum total bilirubin levels (1.4 vs. 6.3 mg/dL) and on CT scan,
      had larger, well-localized tumors (5 cm vs. 2 cm). Their postoperative course was
      better with no mortality or major morbidity, whereas after resection for
      carcinoma 7 (6.3%) patients died and 30 (27%) had major postoperative
      complications. Thus, a tumor of this region in a young patient with indolent
      history, low bilirubin level and with CT scan depicting a large expansile lesion
      suggests a carcinoid. Such tumors may be safely resected with low postoperative
      morbidity and mortality and good long-term prognosis.

PMID- 16974041
TI  - Hepatic adenomatosis--a rare double complication of multiple adenoma rupture and
      malignant transformation.
AB  - Hepatic adenomatosis (HA) is a rare disorder that is susceptible to hemorrhagic
      complications and, rarely, to malignant transformation. We report a 24-year-old
      woman who was found to have HA with > 10 tumors; she presented with simultaneous
      rupture of two of the adenomas, along with malignant change in one. Hematoma
      evacuation and caudate lobe resection were done and she has been doing well 6
      months later.

PMID- 16974042
TI  - Colitis due to Ancylostoma duodenale.
AB  - The larva of hookworm matures into the adult stage in the small intestine,
      causing chronic intestinal blood loss and iron-deficiency anemia. Hookworm
      infestation of colon has not been reported previously. We report a 35-year-old
      man who presented with diarrhea with blood and mucus in stools. Colonoscopy
      revealed several hookworms in the colon firmly adherent to the mucosa, with
      oozing of blood and surrounding mucosal erosions. He was treated with mebendazole
      and symptoms recovered completely.

PMID- 16974043
TI  - Laparoscopic control of spontaneous external hemorrhage from umbilical varix.
AB  - Spontaneous external hemorrhage from an umbilical varix is rare. We describe a 40
      year-old man with cirrhosis and portal hypertension, who presented with recurrent
      external bleeding from an umbilical varix. The first episode was controlled by
      transfixation of the vein under local anesthesia. Contrast-enhanced CT scan
      demonstrated a hugely distended recanalized umbilical vein arising from the left
      branch of the portal vein and ending in the umbilical cicatrix. Recurrent
      bleeding necessitated laparoscopy and in-situ clipping of the bleeding vein in
      the falciform ligament. At six months' follow up the patient has no further
      bleeding.

PMID- 16974044
TI  - Malignant lymphoma of stomach associated with duodenal carcinoid.
AB  - We report a 73-year-old man with diffuse large B-cell lymphoma of the stomach in
      whom distal gastrectomy specimen revealed coexisting carcinoid tumor of the
      duodenum. Postoperatively the patient received six cycles of chemotherapy (CHOP
      regimen) and was asymptomatic nine months later.

PMID- 16974045
TI  - Nasal septum perforation: rare manifestation of Crohn's disease.
AB  - We report a 25-year-old man with four-year history of weight loss, diarrhea and
      intermittent epistaxis. Endoscopy and biopsy showed inflammation of the nasal
      mucosa. Endoscopic and histologic diagnosis of Crohn s disease was made later;
      the granulomatous nasal lesions responded to sulfasalazine and azathioprine.

PMID- 16974046
TI  - Primary transitional cell carcinoma of spleen.
AB  - Transitional cell carcinoma arises from the lining of the urogenital tract and
      ovary. We report a 39-year-old lady with transitional cell carcinoma of the
      spleen that presented as a complex cystic lesion. Exhaustive search for another
      primary was negative. She is doing well 18 months after splenectomy was
      performed.

PMID- 16974047
TI  - NSAIDs and Helicobacter pylori association in patients with bleeding peptic
      ulcers.

PMID- 16974048
TI  - Palliative treatment of malignant esophageal, esophagogastric junction and
      anastomotic strictures with self-expandable stents.

PMID- 16974049
TI  - Expression of ubiquitin-protein ligases and their substrates in malignant gastric
      and colonic tumors.

PMID- 16974050
TI  - Hepatitis B genotypes virus among chronically infected patients in a tertiary
      care hospital in Bangladesh.

PMID- 16974051
TI  - Bone turnover markers in prepubertal children with classical galactosemia.

PMID- 16974052
TI  - Comparative evaluation of "Sublay" versus "Onlay" meshplasty in ventral hernias.

PMID- 16974053
TI  - Hepatocellular carcinoma and cholangiocarcinoma are associated with high serum
      levels of hepatocyte growth factor.

PMID- 16974054
TI  - Selectin gene polymorphisms in IgA nephropathy.

PMID- 16974055
TI  - Regulation of body weight by leptin, with special reference to hypoxia-induced
      regulation.
AB  - Since first cloned and reported by Zhang et al in 1994 (Nature 372:425), the
      obese gene and its product-leptin has been studied profoundly. Our knowledge in
      body weight regulation and the role played by leptin has increased substantially.
      Leptin serves as an adiposity signal to inform the brain of the adipose tissue
      mass in a negative feedback loop regulating food intake and energy expenditure.
      Many articles have reported weight loss at high altitude, but the explanation has
      been limited to loss of appetite. New ideas were highlighted after studies by
      Grosfeld et al and Ambrosini et al on the obese gene under hypoxia condition.
      Cells with hypoxia treatment upregulated obese gene transcription and suggested
      that enhancement of leptin secretion in vivo under hypoxia environment may be one
      of the potential therapeutic methods for obesity treatment.

PMID- 16974056
TI  - Impact of selectin gene polymorphisms on rapid progression to end-stage renal
      disease in patients with IgA nephropathy.
AB  - OBJECTIVE: It is evident that leukocyte infiltration plays an important role in
      the pathogenesis of IgA nephropathy (IgAN). Selectin is one of the key adhesion
      molecules involved in leukocyte infiltration. Recent studies demonstrated a
      significant association between the selectin gene polymorphisms and
      susceptibility to IgAN. However, the impact of selectin gene polymorphisms on the
      progression to end-stage renal disease (ESRD) has not been studied. PATIENTS AND
      METHODS: To evaluate the influence of the selectin gene polymorphisms on the
      progression of IgAN, we designed specific primers for PCR genotyping and analyzed
      the association of selectin gene polymorphisms with the declining rate in renal
      function to its ESRD. RESULTS: A total of 61 hemodialysis patients were enrolled
      in the study. The mean age at renal biopsy was 33.0+/-13.3 years old, and the
      mean age at the start of hemodialysis was 41.2+/-13.8 years old. The mean
      interval between the time points of renal biopsy and the start of hemodialysis
      was 8.2+/-6.5 years (ranging from 0 to 33 years). The interval was significantly
      longer in IgAN patients with a homoallele of C in C1402T, C1402/C1402, of the E
      selectin gene, or a homoallele of C in C712T, C712/C712, of the L-selectin gene
      compared to others. The haplotype, which is a combination of C1402/C1402 and
      C712/C712, is able to distinguish the group that is at least a better prognosis
      than the severest prognostic one. CONCLUSION: This study provides a possible
      association between the selectin gene polymorphisms and the rapid progression to
      ESRD in IgAN patients.

PMID- 16974057
TI  - A patient with early syphilis complicated by fatty liver who showed an
      alleviation of hepatopathy accompanied by jaundice after receiving anti
      syphilitic therapy.
AB  - A 42-year-old male with visceral obesity and a fatty liver presented with
      hepatopathy accompanied by jaundice and was diagnosed to have early syphilis
      based on the results of standard serologic tests and clinical findings. Both the
      subjective and objective findings including hepatopathy were rapidly alleviated
      by anti-syphilitic therapy. Severe hepatopathy accompanied by jaundice used to be
      considered a rare complication. However, due to contemporary unhealthy lifestyle
      patterns characterized by hypernutrition and a lack of exercise the occurrence of
      fatty liver is now dramatically increasing. Our findings suggest that the
      occurrence of fatty liver can exacerbate the damage to the hepatic parenchyma due
      to a Treponema pallidum infection.

PMID- 16974058
TI  - Aortic dissection associated with acute myocardial infarction and stroke found at
      autopsy.
AB  - It is sometimes very difficult to diagnose dissecting aortic aneurysms in the
      early stage. We report an autopsy case in which an acute myocardial infarction
      and cerebral infarction simultaneously occurred and the symptoms were transiently
      ameliorated in a patient with an acute aortic dissection.

PMID- 16974059
TI  - Adrenal insufficiency complicated with antiphospholipid syndrome (APS).
AB  - We describe a 69-year-old woman with bilateral adrenal hemorrhage complicated
      with antiphospholipid syndrome (APS). She was hospitalized with nausea and
      vomiting in September 2003. Laboratory data demonstrated hyponatremia,
      hypoglycemia and prolongation of activated partial thromboplastin time (aPTT).
      Abdominal computed tomography showed bilateral adrenal enlargement. In October
      2003, she demonstrated altered mental status with progressive hyponatremia, a
      high level of ACTH, and a low level of serum cortisol. She also showed
      thrombocytopenia, anti-cardiolipin IgG antibody, anti-beta2GPI antibody, and
      lupus anticoagulants. After four months, anti-cardiolipin IgG antibody was still
      positive. Based on these findings, she was diagnosed as having APS complicated
      with adrenal insufficiency due to hemorrhagic infarction. After treatment with
      corticosteroid, a low dose of aspirin and normal saline infusion, her condition
      quickly improved. Platelet counts and aPTT were also normalized. To our
      knowledge, this is the second Japanese case of APS complicated with bilateral
      adrenal hemorrhage. APS should be considered an important underlying cause of
      adrenal insufficiency.

PMID- 16974060
TI  - Small intestinal metastasis from small cell lung cancer.
AB  - A 71-year-old man who had small cell lung cancer was referred to our institution.
      Before starting chemotherapy, anemia progressed and stool examination was
      positive for occult blood. An abdominal computed tomography scan with contrast
      medium enhancement of the gastrointestinal tract disclosed a small intestinal
      tumor. Histological examination after the surgery confirmed that the tumor was
      metastasis of lung cancer. The patient survived for 3 years after the resection.
      Although clinically apparent metastases of lung cancer to the small intestine are
      rare and are reported to have a poor prognosis, early detection and intervention
      might enhance the chance of survival.

PMID- 16974061
TI  - Pulmonary relapse of non-Hodgkin's lymphoma in bilateral upper lobes.
AB  - We describe a 68-year-old male patient with diffuse large B-cell lymphoma (DLBCL)
      who suffered from relapse in bilateral upper lobes of the lung. The patient
      presented with cough, weakness and fever. A bronchovascular-lymphangitis-like
      shadow was detected in the bilateral upper lobes on a chest roentgenogram.
      Although cytological and cytofluorometric examinations revealed no malignant
      cells in the bronchoalveolar lavage fluid, trans-bronchial lung biopsy (TBLB)
      showed involvement of DLBCL in the bronchial mucosa. Recurrent lymphoma tends to
      extend along the bronchovascular bundles, resulting in granulomatous
      consolidation that may mimic tuberculosis and is likely to involve the lower
      lobes. Thus, TBLB proved to be essential for the diagnosis of the lung
      involvement of non-Hodgkin's lymphoma (NHL).

PMID- 16974062
TI  - Adenovirus fulminant hepatic failure: disseminated adenovirus disease after
      unrelated allogeneic stem cell transplantation for acute lymphoblastic leukemia.
AB  - Adenovirus is one of the major causes of non-relapse morbidity and mortality
      after allogeneic hematopoietic stem cell transplantation for hematological
      malignancy. Fulminant hepatic failure is a rare manifestation of post-transplant
      complication with adenovirus. Extremely high mortality and aggressiveness of the
      clinical course have been posing clinical challenges for the diagnosis as well as
      for the treatment. Here, we report a case with disseminated adenovirus disease
      presenting with fulminant hepatic failure after bone marrow transplantation for
      acute lymphoblastic leukemia.

PMID- 16974063
TI  - CADASIL with a novel mutation in exon 7 of NOTCH3 (C388Y).
AB  - We report a 38-year-old Japanese woman who had cerebral autosomal dominant
      arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with a
      novel mutation (TGT to TAT) at nucleotide position 1241 (C388Y) in exon 7 of the
      Notch3 gene (NOTCH3). Immunostaining of a skin biopsy with a Notch3 monoclonal
      antibody is a beneficial method for the screening of CADASIL, particularly in the
      case of rare mutations outside the mutation hotspots in NOTCH3 as shown in this
      patient.

PMID- 16974064
TI  - Squamous papillomas in the trachea and main bronchi found in a Cowden's disease
      patient.

PMID- 16974065
TI  - Systemic infection due to Acremonium after allogeneic peripheral blood stem cell
      transplantation.

PMID- 16974066
TI  - Effect of d-pseudoephedrine on cough reflex and its mode of action in guinea
      pigs.
AB  - d-Pseudoephedrine (PSE) is one of the main ingredients of Ephedrae herba.
      Although PSE is widely applied for patients with a common cold and upper
      respiratory inflammation as a decongestant, the effects of PSE on cough have
      never been reported. In this study, we investigated the antitussive effects of
      intraperitoneal injection of PSE on the cough reflex induced by microinjection of
      citric acid into the larynx of guinea pigs. PSE decreased the number of cough
      reflexes dose-dependently (-18.3 +/- 5.0% at 20 mg/kg, P<0.05; -41.1 +/- 7.2% at
      60 mg/kg, P<0.01). Furthermore, PSE (60 mg/kg) increased the threshold intensity
      for inducing fictive cough by electrical micro-stimulation of the nucleus tractus
      solitarius (+72.7 +/- 8.4%, P<0.01). On the afferent discharge of the superior
      laryngeal nerve, PSE suppressed the increases of amplitude and frequency when
      stimulated by citric acid at laryngeal mucosa. These results demonstrate that PSE
      possesses an antitussive effect that might be derived from both central and
      peripheral actions.

PMID- 16974067
TI  - Effects of bifemelane on the calcium level and ATP release of the human origin
      astrocyte clonal cell.
AB  - The effect of bifemelane hydrochloride (bifemelane) was examined on human origin
      astrocyte clonal cells (Kings-1). Bifemelane (125 - 1,000 microM) induced a dose
      dependent increase in the intracellular calcium concentration ([Ca(2+)](i)). In
      the highest concentration (1,000 microM), the drug caused the second large
      increase in [Ca(2+)](i) during the washing. The increase that occurred during the
      administration partially remained in the Ca(2+)-free medium and was blocked by 2
      aminoethoxydiphenyl borate (2-APB), an IP(3)-receptor blocker, indicating that
      the source of Ca(2+) for the increase could be ascribed to the intracellular
      store. The increase in [Ca(2+)](i) was not observed during washing with Ca(2+)
      free medium, but was observed when the washing was performed with Ca(2+)
      containing medium. Bifemelane caused a dose-dependent ATP release, but histamine
      and carbachol, which induced a large increase in [Ca(2+)](i), had no effects on
      the ATP release. The effects on the [Ca(2+)](i) were blocked by pretreatment with
      pyridoxal phosphate-6-azophenyl-2',4' disulfonic acid, a P2-receptor antagonist.
      Although the mechanisms of ATP release induced by the drug have not been
      elucidated yet, the present results demonstrate that the increase in [Ca(2+)](i)
      induced by bifemelane is not due to its direct effect on the cells, but is
      dependent upon the ATP released from the cells.

PMID- 16974068
TI  - The novel Src kinase inhibitor M475271 inhibits VEGF-induced vascular endothelial
      cadherin and beta-catenin phosphorylation but increases their association.
AB  - M475271, 4-quinazolinamine, N-(2-chloro-5-methoxyphenyl)-6-methoxy-7-[(1-methyl-4
      piperidinyl) methoxy]-(9Cl), is a new anilinoquinazoline derivative that displays
      selective inhibition of Src kinase activity and tumor growth in vivo. Vascular
      endothelial growth factor (VEGF)-induced angiogenesis plays a pivotal role in
      tumor growth and metastasis. Vascular endothelial (VE)-cadherin is an endothelial
      cell-specific adhesion molecule that can interact with the cytoskeleton via
      several anchoring molecules such as beta-catenin. Here, we examined the effect of
      M475271 on VE-cadherin and beta-catenin phosphorylation and association. We also
      examined its effect on VEGF-induced human umbilical vein endothelial cell (HUVEC)
      proliferation, migration, and tube formation. The findings reveal pretreatment
      with M475271 significantly inhibits VEGF-induced VE-cadherin and beta-catenin
      phosphorylation. However, M475271 significantly increases VE-cadherin and beta
      catenin association compared to the VEGF-treated group. Confocal laser
      microscopic examination confirmed the augmentation effect of M475271 on VE
      cadherin and beta-catenin association. Finally, M475271 was shown to have
      inhibitory effects comparable to those of PP2 and Herbimycin A on VEGF-induced
      HUVEC proliferation, migration, and tube formation. These findings suggest that
      M475271 attenuates VEGF-induced angiogenesis by maintaining cell-cell junction
      stability. Although the involvement of other signaling molecules cannot be ruled
      out, M475271 has potential as a drug for the inhibition of the angiogenesis
      needed for tumor growth and metastasis.

PMID- 16974069
TI  - Identification of amino acid residues important for sarpogrelate binding to the
      human 5-hydroxytryptamine2A serotonin receptor.
AB  - The purpose of the present study was to examine 5-hydroxytryptamine (5-HT)(2A)
      receptor sarpogrelate interactions by site-directed mutagenesis. Based on
      molecular modeling studies, aspartic acid (Asp)155[3.32] and tryptophan
      (Trp)151[3.28] in transmembrane helix (TMH) III and Trp336[6.48] in TMH VI of the
      5-HT(2A) receptor were found to interact with sarpogrelate. All of these residues
      were mutated to alanine (Ala). The Asp3.32Ala mutant did not exhibit any affinity
      for [(3)H]ketanserin, whereas the Trp3.28Ala mutant showed a markedly decrease in
      the binding affinity for [(3)H]ketanserin (K(d) >10,000 nM). Therefore, it was
      not possible to find any sarpogrelate affinity to the mutants using
      [(3)H]ketanserin. The mutation also abolished agonist-stimulated formation of
      [(3)H]inositol phosphates (IP) in both cases. On the other hand, the Trp6.48Ala
      mutant showed reduced binding affinity for [(3)H]ketanserin (K(d) 2.0 nM vs 0.8
      nM for the wild-type receptor) and had reduced affinity for sarpogrelate (pK(i)
      value of 5.71 vs 9.06 for the wild-type receptor). The Trp6.48Ala mutant also
      showed the greatest decrease in sensitivity to sarpogrelate (pK(b) value 8.81 for
      wild-type and 5.11 for mutant) in inhibiting agonist-stimulated IP formation.
      These results provide direct evidence that Asp3.32, Trp3.28, and less
      importantly, Trp6.48 are responsible for the interaction between the 5-HT(2A)
      receptor and sarpogrelate. In addition, these results support the findings
      obtained from molecular modeling studies.

PMID- 16974070
TI  - Analysis of cytogenetic damage in rice seeds induced by energetic heavy ions on
      ground and after spaceflight.
AB  - To analyze the biological effects of the space environment, we flew nine lines of
      rice seeds on the Chinese 20(th) recoverable satellite for a duration of 18 days.
      The same lines of seeds were also irradiated to low doses (2.0 mGy) of Carbon, or
      Neon or Iron ions (with different LET value of 13.3 keV/microm, 31 keV/microm and
      500 keV/microm respectively) at National Institute of Radiological Sciences in
      Chiba, Japan. The total number of mitotic cells and chromosomal aberrations were
      analyzed. The mitotic index (MI) and the frequency of chromosomal aberration were
      evaluated in order to compare the cytogenetic damages from spaceflight and from
      exposure to similar doses of charged particle on the ground. The results of the
      present study show that the space environment and heavy energy ion can alter cell
      growth, and induce various chromosome aberrations including micronuclei,
      chromosomal bridges, fragments and laggards. With all the lines combined, the
      frequency of chromosome aberrations and MI in seeds flown in space are the
      highest. The effectiveness of cytogenetic damage from spaceflight (SP) and the
      heavy ion irradiations is SP > Fe > Ne > C.

PMID- 16974071
TI  - Transcriptional response of wild-type and ataxia telangiectasia lymphoblasts
      following exposure to equitoxic doses of ionizing radiation.
AB  - Experiments were designed to compare the transcriptional response to ionizing
      radiation (IR) of wild-type (WT) and ataxia telangiectasia (AT) cells. mRNA
      levels were assessed 2, 4 and 24 h after exposure to equitoxic doses using cDNA
      microarrays. Data reveal distinct patterns of gene expression between AT and WT
      cells since IR-responsive genes were mostly cell-type specific, this group
      representing 87 and 94% of the responding genes in WT and AT cells, respectively.
      In both cell lines, transcriptional alterations of genes associated with
      proliferation correlated with the observed cell cycle and growth data.
      Deregulated genes involved in apoptosis suggest that wild-type cells were more
      prone to cell death by apoptosis than AT cells. Furthermore, genes associated
      with the response to oxidative stress were particularly deregulated in wild-type
      cells whereas alterations of genes related to unexpected pathways including RNA
      processing, protein synthesis and lipid metabolism were specifically found in
      irradiated AT cells. These data suggest that under radiation conditions leading
      to a similar survival of WT and AT cells, the mechanisms triggered after
      radiation were mainly dependent on ATM status and thus on the intrinsic
      radiosensitivity.

PMID- 16974072
TI  - Crucial role of SDF-1/CXCR4 interaction in the recruitment of transplanted dermal
      multipotent cells to sublethally irradiated bone marrow.
AB  - Our previous study indicated that dermal multipotent cells (DMCs) could engraft
      into bone morrow (BM) of rats with sublethal irradiation and promote
      hematopoietic recovery after being transplanted systemically, but the mechanisms
      determining the recruitment of DMCs to the irradiation injured BM remain unclear.
      In the present study, we investigated the role of stromal cellderived factor-1
      (SDF-1)/CXCR4 interaction in this process. Male DMCs were isolated and
      transplanted into female rats systemically, and by employing quantitative real
      time TaqMan polymerase chain reaction for the sex-determining region of Y
      chromosome, it was found that the amount of DMCs in BM of rats with sublethal
      irradiation was about 3 times more than that of normal rats (P < 0.01).
      Incubation of DMCs with AMD3100 before transplantation, which specifically blocks
      binding of SDF-1 to its endogenous receptor CXCR4, diminished recruitment of DMCs
      to the injured BM by 57.2 +/- 5.5% (P < 0.05). In addition, it was confirmed that
      the expression of SDF-1 in injured BM was up-regulated when compared with that in
      normal BM, and in vitro analysis revealed that BM extracts from irradiated rats
      had a strong chemotactic effect on DMCs, which decreased significantly when DMCs
      were pre-incubated with AMD3100 (P < 0.05). These data suggest that transplanted
      DMCs were recruited more frequently to irradiation-injured BM than normal BM and
      the interactions of SDF-1/CXCR4 played an important role in this process.

PMID- 16974073
TI  - Prevention and reversal of diabetic nephropathy in db/db mice treated with
      alagebrium (ALT-711).
AB  - BACKGROUND: Alagebrium (ALT-711) has been shown to improve renal dysfunction in
      animal models of diabetes. METHODS: To test its effects in diabetic nephropathy
      (DN), ALT-711 was administered (1 mg/kg daily i.p.) to 9-week-old female db/db
      mice (n = 15, group A1) for 3 weeks and to 3-month-old (n = 15, group A2), 7
      month-old (n = 7, group A3), and 12-month-old (n = 5, group A4) female db/db mice
      for 12 weeks, while a similar number of diabetic and nondiabetic mice were used
      as controls. The epsilonN-carboxymethyllysine (CML) levels in serum, urine, skin,
      and kidney tissue were measured by enzyme-linked immunosorbent assay. The renal
      morphometric parameters were assessed by electron and light microscopy. RESULTS:
      By the 3rd week of treatment, the serum CML level decreased by 41%, and the
      urinary CML concentration increased by 138% from baseline, while the urinary
      albumin/creatinine ratio was lower (p < 0.05) in diabetic and nondiabetic group
      A1 mice. After 3 months of treatment, serum, skin, and kidney CML levels and
      urinary albumin/creatinine ratio were lower (p < 0.05) and the urinary CML levels
      higher (p < 0.05) in treated group A2, A3, and A4 animals compared with groups
      which received phosphate-buffered saline, with a similar pattern observed in
      nondiabetic mice. The renal morphological parameters characteristic of DN
      decreased in treated compared with untreated mice. CONCLUSION: Alagebrium may
      prevent, delay, and/or reverse established DN in db/db mice by reducing the
      systemic advanced glycation end product pools and facilitating the urinary
      excretion of advanced glycation end products.

PMID- 16974076
TI  - Radiation hybrid mapping of three candidate genes for bovine Neuronal Ceroid
      Lipofuscinosis: CLN3, CLN5 and CLN6.

PMID- 16974077
TI  - FISH-mapping of LEP and SLC26A2 genes in sheep, goat and cattle R-banded
      chromosomes: comparison between bovine, ovine and caprine chromosome 4
      (BTA4/OAR4/CHI4) and human chromosome 7 (HSA7).
AB  - Sheep (OAR), goat (CHI) and cattle (BTA) R-banded chromosome preparations,
      obtained from synchronized cell cultures, were used to FISH-map leptin (LEP) and
      solute carrier family 26 member 2 (SLC26A2) genes on single chromosome bands. LEP
      maps on OAR4q32 and CHI4q32, being the first assignment of this gene to these two
      species. SLC26A2 maps on BTA7q24, OAR5q24 and CHI7q24. This gene, too, was
      assigned for the fist time to both sheep and goat chromosomes, while it was more
      precisely localized on a single chromosome band in cattle. Improved cytogenetic
      maps of BTA4/OAR4/CHI4 were constructed and compared with HSA7 revealing five
      main conserved segments and complex chromosome rearrangements, including a
      centromere repositioning, differentiating HSA7 and BTA4/OAR4/CHI4.

PMID- 16974078
TI  - Calreticulin as a new histone binding protein in mitotic chromosomes.
AB  - Calreticulin (CRT) is a multifunctional Ca(2+)-binding protein that mainly
      functions in the endoplasmic reticulum as a molecular chaperone for newly
      synthesized proteins. Recently we reported the protein composition of human
      metaphase chromosomes (Uchiyama et al., 2004), which included CRT. Here we
      describe new characteristics of CRT in vitro as well as its localization on the
      surface of metaphase chromosomes in vivo. CRT was detected in the chromosomal
      fraction by Western blotting and its binding partners were identified as core and
      linker histones by ligand overlay assay. Surface plasmon resonance sensor
      analyses revealed that CRT is bound to chromatin fibers. Moreover, we found that
      CRT has both supercoiling activity, which assists core histone assembly into
      chromatin fibers, and binding ability to histone H2A/H2B dimers and histone H3/H4
      tetramers. Unlike the chromosome scaffold proteins, indirect immunofluorescent
      staining revealed that CRT is located on the surface of metaphase chromosomes.
      These results suggest that CRT plays a role which involves chromatin dynamics on
      the surface of mitotic chromosomes.

PMID- 16974079
TI  - Chromosomal alterations in 98 endometrioid adenocarcinomas analyzed with
      comparative genomic hybridization.
AB  - The aim of the present study was to investigate chromosomal alterations in a
      large set of homogeneous tumors, 98 endometrioid adenocarcinomas. We also wanted
      to evaluate differences in chromosomal alterations in the different groups of
      tumors in relation to stage, survival and invasive or metastatic properties of
      the tumors. Comparative genomic hybridization (CGH) was used to detect
      chromosomal alterations in tissue samples from 98 endometrioid adenocarcinomas.
      All chromosomes were involved in DNA copy number variations at least once in the
      tumor material, but certain changes were recurrent and rather specific. Among the
      specific changes, it was possible to identify 39 chromosomal regions displaying
      frequent DNA copy number alterations. The most frequent alteration was detected
      at 1q25-->q42, in which gains were found in 30 cases (30%). Gains at 19pter-
      >p13.1 were detected in 26 tumors (26%) and at 19q13.1-->q13.3 in 19 tumors
      (19%). Increased copy numbers were also detected at 8q (8q21-->q22 and 8q22-
      >qter), at a relatively high rate, in 17 cases (17%). Furthermore, gains at 10q21
      ->q23 and 10p were found in 14 (14%) and 13 cases (13%), respectively. The most
      common losses were found in the three regions 4q22-->qter, 16q21-->qter and 18q21
      ->qter, all of which were detected in eight of the 98 tumors (8%). We also
      detected differences between the tumors from deceased patients and from
      survivors. Gain at 1q25-->q42 was more commonly detected in the tumors from
      patients who died of cancer. We noted that the regions most affected differed in
      the different surgical stages (I-IV). The results of the CGH analysis identify
      specific chromosomal regions affected by copy number changes, appropriate objects
      for further genetic studies.

PMID- 16974080
TI  - Genomic organization and expression pattern of scapinin (PHACTR3) in mouse and
      human.
AB  - Scapinin has been found to bind to cytoplasmic actin and is also a putative
      regulatory subunit of protein phosphatase-1 (PP1). It is found attached to the
      nuclear matrix-intermediate filament (NM-IF) and is down-regulated by
      differentiation of tumor cells. We have analyzed the genomic structure and tissue
      specific expression pattern of both the human scapinin gene (PHACTR3) and the
      orthologous mouse gene. Both genes showed a highly conserved complex genomic
      organization with four different leader exons. Alternative splicing of exon 5 was
      found to be limited to human and variable polyadenylation in mouse transcripts
      only. In both species expression seems to occur predominantly in the brain. By
      Northern blot analysis two major transcripts in human and three transcripts in
      mouse were detected. Expression analysis in the mouse revealed a tissue-specific
      complex transcription pattern in the brain and a specific pattern was observed
      during prenatal development. Based on the transcriptional data we therefore
      assume scapinin to have a distinct biological function in the mammalian brain.

PMID- 16974081
TI  - Atypical mutational properties of human chromosome 21 suggested by comparative
      genome-scale analyses.
AB  - Mutation of genetic material is a necessary component of evolutionary change.
      There is evidence for both intragenome and intergenome heterogeneity in terms of
      mutation frequencies. Reported comparisons of DNA sequence differences between
      human and chimpanzee (Pan troglodytes) suggest that human chromosome 21 may
      exhibit mutational hypervariability relative to the other autosomes. In the
      present study, further evidence is provided for such hypervariability based on
      large-scale analyses of amino acid composition of (translated) human genes and
      pseudogenes. A comparison of the variation in the above cases (i.e., DNA sequence
      differences and amino acid composition differences) yields similar ratios (1.2
      1.4) for chromosome 21 relative to the other autosomes, e.g., human chromosome 22
      - an autosome that is more typical in this respect and is of similar size to 21.
      Human chromosome 21 is also presented in this study as being atypical in terms of
      reported associations between mutation rates and GC content or CpG dinucleotides.
      In terms of GC distribution patterns, a comparison of NT_011512 and NT_011520
      contigs revealed a lower heterogeneity for human chromosome 21 relative to 22.
      Possible hypermutability of chromosome 21 is further discussed in the context of
      GC patterns, reported long interspersed nuclear element content (LINE1s), and the
      implications of these parameters for chromatin structure.

PMID- 16974082
TI  - The role of caspases in photoreceptor cell death of the retinoschisin-deficient
      mouse.
AB  - Early schisis cavities in the retinal bipolar cell layer accompanied by
      progressive loss of cone and rod photoreceptor cells are the hallmark of the
      retinoschisin-deficient (Rs1h(-/Y)) murine retina. With this study we aimed at
      elucidating the molecular events underlying the photoreceptor cell death in this
      established murine model of X-linked juvenile retinoschisis. We show that
      photoreceptor degeneration in the Rs1h(-/Y) mouse is due to apoptotic events
      peaking around postnatal day 18. Cell death is accompanied by increased
      expression of initiator and inflammatory caspases but not by downstream effector
      caspases. The strong induction of caspase-1 (Casp1) prompted us to explore its
      involvement in the apoptotic process. We therefore generated double knock-out
      mice deficient for both retinoschisin and Casp1. No direct influence of the Casp1
      genotype on apoptosis could be identified although striking differences in the
      overall number of resident microglia were observed independent of the Rs1h
      genotype.

PMID- 16974083
TI  - YAC/BAC contig spanning the MHC class III region of cattle.
AB  - A contig of the class III region of the bovine major histocompatibility complex
      (MHC) was established from bacterial and yeast artificial chromosomes using PCR
      and BAC-end sequencing. The marker content of individual clones was determined by
      gene and BAC-end specific PCR, and the location of genes and BAC-ends was
      confirmed analyzing somatic hybrid cells. A comparative analysis indicated that
      the content and order of MHC class III genes is strongly conserved between cattle
      and other mammalian species. Fluorescence in situ hybridization localized the
      bovine class III region to BTA23q21-->q22. The results show that the collection
      of sequenced BAC-ends is a powerful resource for generating high-resolution
      comparative chromosome maps.

PMID- 16974084
TI  - Genomic structure of swine taste receptor family 1 member 3, TAS1R3, and its
      expression in tissues.
AB  - Taste receptor family 1 member 3, TAS1R3, is shown to be involved in sweet and
      umami tastes in mouse, and the nucleotide sequence of the gene has been reported
      in rat, gorilla, and human. Pigs are frequently used as models for human
      diseases, and are also considered to be source animals for xenotransplantation to
      humans due to their anatomical and physiological similarities to humans.
      Therefore, in the present study, the genomic structure of the swine TAS1R3 gene
      was determined, and TAS1R3 expression was studied in various swine tissues. The
      gene was shown to reside on swine chromosome 6q22-->q23, from which three types
      of mRNAs were generated: 3,752 bp derived from six exons in tongue, 3,704 bp from
      six exons and 3,630 bp from seven exons in testis. The 6 exons/5 introns were
      structurally similar to those of humans and mice, but the 7 exons/6 introns
      structure of TAS1R3 was first observed in swine. High expressions of TAS1R3 were
      revealed in tongue, kidney, and testis by real-time PCR. The expression profile
      of the tissues except for kidney was similar to that of mouse. When in situ
      hybridization using an RNA probe for TAS1R3 was performed on swine tongue and
      testis tissues, TAS1R3 expressions were revealed in tongue circumvallate
      papillae, fungiform papillae, mucosal epithelium, follicular B lymphocytes,
      lymphocytes in submucosal tissues of lingual tonsil, and spermatogenic cells.
      Using peripheral mature B lymphocytes, the expression of TAS1R3 in B lymphocytes
      was further confirmed by real-time PCR and sequencing of the real-time PCR
      product.

PMID- 16974085
TI  - Characterization of two whey protein genes in the Australian dasyurid marsupial,
      the stripe-faced dunnart (Sminthopsis macroura).
AB  - We report the first isolation and sequencing of genomic BAC clones containing the
      marsupial milk protein genes Whey Acidic Protein (WAP) and Early Lactation
      Protein (ELP). The stripe-faced dunnart WAPgene sequence contained five exons,
      the middle three of which code for the WAPmotifs and four disulphide core domains
      which characterize WAP. The dunnart ELPgene sequence contained three exons
      encoding a protein with a Kunitz motif common to serine protease inhibitors.
      Fluorescence in situ hybridization located the WAPgene to chromosome 1p in the
      stripe-faced dunnart, and the ELPgene to 2q. Northern blot analysis of lactating
      mammary tissue of the closely related fat-tailed dunnart has shown asynchronous
      expression of these milk protein genes. ELPwas expressed at only the earlier
      phase of lactation and WAPonly at the later phase of lactation, in contrast to
      beta-lactoglobulin (BLG) and alpha-lactalbumin (ALA) genes, which were expressed
      in both phases of lactation. This asynchronous expression during the lactation
      cycle in the fat-tailed dunnart is similar to other marsupials and it probably
      represents a pattern that is ancestral to Australian marsupials.

PMID- 16974086
TI  - Karyotype differentiation in Chromaphyosemion killifishes (Cyprinodontiformes,
      Nothobranchiidae). II: cytogenetic and mitochondrial DNA analyses demonstrate
      karyotype differentiation and its evolutionary direction in C. riggenbachi.
AB  - African killifishes of the genus Chromaphyosemion show a high degree of
      phenotypic and karyotypic diversity. The latter is especially pronounced in C.
      riggenbachi, a morphologically defined species restricted to a small distribution
      area in Cameroon. This study presents a detailed reconstruction of karyotype
      differentiation within C. riggenbachi using conventional Giemsa staining and
      sequential chromosome banding as well as a phylogenetic analysis based on part of
      the mitochondrial (mt) cytochrome b gene from eleven populations. The cytogenetic
      analysis revealed differences in chromosome morphology, banding patterns and/or
      diploid chromosome number (2n) among all populations examined. Diploid number
      ranged from 2n = 20 to 2n = 36 and varied mainly among populations, while C
      banding patterns and NOR phenotypes showed fixed differences among populations as
      well as some variability within populations. The mtDNA analysis disclosed five
      clearly differentiated haplotype groups. Mapping the karyotype data onto the
      mtDNA dendrogram revealed a decrease in 2n from the most basal to the most
      derived groups, thus demonstrating a reduction of 2n during their evolutionary
      history. Our results indicate that karyotype differentiation involved
      Robertsonian fusions as well as non-Robertsonian processes. Causes of the high
      karyotypic variability may include an elevated chromosomal mutation rate as well
      as certain features of the ecology and mating system that could facilitate the
      fixation of chromosomal rearrangements. The pattern of karyotype and haplotype
      differentiation and the results of previous crossing experiments suggest
      incipient speciation in C. riggenbachi.

PMID- 16974087
TI  - Characterization of a de novo complex chromosome rearrangement (CCR) involving
      chromosomes 2 and 12, associated with mental retardation and impaired speech
      development.
AB  - We report on a currently six-year-old patient with a de novo complex chromosome
      rearrangement (CCR) involving chromosomes 2 and 12. A translocation 2;12 that
      appeared to be reciprocal after standard banding turned out to be a complex event
      with seven breaks after molecular cytogenetic analyses. Array CGH analysis showed
      no imbalances at the breakpoints but revealed an additional microdeletion of
      about 80 kb on chromosome 11. The same deletion was also present in the
      phenotypically normal father. The patient showed relatively mild mental
      retardation, defined mainly as impaired speech development (orofacial dyspraxia)
      and psychomotor retardation. In addition, mild dysmorphic facial features like
      hypertelorism, a prominent philtrum and down-turned corners of the mouth were
      observed. We narrowed down all breakpoint regions to about 100 kb, using a panel
      of mapped bacterial artificial chromosome (BAC) clones for fluorescence in situ
      hybridization (FISH). BACs spanning or flanking all seven breakpoints were
      identified and no chromosomal imbalances were found consistent with the array CGH
      results. Our investigations resulted in the following karyotype:
      46,XY,t(2;12)(2pter-->2p25.3::2p23.3-->2p25.2::2p23.3-->2p14::2q14.3-
      >2p14::2q14.3-->2q14.3::12q 12-->12qter;12pter-->12q12::2p25.3-->2p25.2::2q14.3-
      >2qter).

PMID- 16974088
TI  - Dynamic increase of a 45,X cell line in a patient with multicentric ring Y
      chromosomes.
AB  - Because ring Y chromosomes are unstable during cell division most reported
      patients are mosaics, usually including a 45,X cell line. The phenotype varies
      from normal males or females with streak gonads to sexual ambiguities. We present
      here the case of a 23-year-old man who was referred at 11 years for growth delay.
      The GTG-banded karyotypes of lymphocytes revealed two cell lines: 46,X,dic r(Y)
      seen in 76% of the metaphases analyzed and 45,X (24%). Karyotypes and FISH were
      performed eight years later with the following probes: DYZ3 (Y centromere), SRY
      (sex-region of the Y), DYZ1 (Yq heterochromatin), CEPX/Y (X centromere and Yq
      heterochromatin), TelVysion Xp/Yp, Xq/Yq (X and Y subtelomeres), pan-telomeric,
      cosmid clones LLycos130G04 and LLycos37C09 (PARII), and BAC clone RP11-5C5
      (Yq11.223). The results showed an increase in the 45,X cell line (60%) and a
      reduction in the 46,X,dic r(Y) cell line (36.4%). The use of Yq probes showed
      that the ring Y chromosome was dicentric. In addition, other ring Y structures
      were observed. The breakpoints occurred in proximal Yp11.32 or in Yp11.31 distal
      to SRY and in Yq12 distal to the PARII region. Therefore, most of the Y remained
      intact and all genes, with the exception of those in PARI, are present in double
      dosage in the dic r(Y). The level of mosaicism was important in defining the
      phenotype.

PMID- 16974089
TI  - A family case of fertile human 45,X,psu dic(15;Y) males.
AB  - We report on a familial case including four male probands from three generations
      with a 45,X,psu dic(15;Y)(p11.2;q12) karyotype. 45,X is usually associated with a
      female phenotype and only rarely with maleness, due to translocation of small Y
      chromosomal fragments to autosomes. These male patients are commonly infertile
      because of missing azoospermia factor regions from the Y long arm. In our
      familial case we found a pseudodicentric translocation chromosome, that contains
      almost the entire chromosomes 15 and Y. The translocation took place in an
      unknown male ancestor of our probands and has no apparent effect on fertility and
      phenotype of the carrier. FISH analysis demonstrated the deletion of the
      pseudoautosomal region 2 (PAR2) from the Y chromosome and the loss of the
      nucleolus organizing region (NOR) from chromosome 15. The formation of the psu
      dic(15;Y) chromosome is a reciprocal event to the formation of the satellited Y
      chromosome (Yqs). Statistically, the formation of 45,X,psu dic(15;Y) (p11.2;q12)
      is as likely as the formation of Yqs. Nevertheless, it has not been described
      yet. This can be explained by the dicentricity of this translocation chromosome
      that usually leads to mitotic instability and meiotic imbalances. A second event,
      a stable inactivation of one of the two centromeres is obligatory to enable the
      transmission of the translocation chromosome and thus a stably reduced chromosome
      number from father to every son in this family.

PMID- 16974090
TI  - The lumbar interspinous ligaments in humans: anatomical study and review of the
      literature.
AB  - In textbooks of human anatomy and atlases of spinal surgery, the lumbar
      interspinous ligaments are described and illustrated in various and often
      conflicting ways. Thirty-four lumbar vertebral columns (19 males, 15 females,
      range 17-92 years old), sampled at autopsy, were studied by dissection and
      macroscopic analysis. The orientation of the fibre bundles was evaluated in the
      sagittal plane by tracing a reference line parallel to the cranial border of the
      spinous process, and the degree of bundle tilting with reference to this line was
      measured in the ventral, middle and dorsal parts of the ligament. Histological
      and immunohistochemical (anti-S100) studies of the ligaments, on sagittal,
      frontal, and transversal planes, were also carried out. In vivo radiological
      validation was performed in 25 patients by MR and CT imaging. Macroscopically,
      the interspinous ligaments are consistently composed of bundles of fibres
      arranged in a characteristic pattern. Together, they present an oblique
      orientation from anterior to posterior in a caudal-cranial direction. In their
      ventral part the bundles form a slight curve with a posterior-inferior concavity.
      In the middle part, the bundles are thicker and arranged in an italic S shape
      with a mean degree of tilting of 52 +/- 14, 21 +/- 12 and 50 +/- 17 in the
      anterior, intermediate and posterior subzones of the L2-L3 ligaments and of 32 +/
      14, 11 +/- 9 and 18 +/- 11 in the anterior, intermediate and posterior subzones
      of the L4-L5 level. The dorsal part consists of obliquely ascending bundles of
      fibres mostly converging in the supraspinous ligament. Histologically, these
      ligaments are mainly composed of collagen fibres, whereas the elastic fibres are
      ubiquitous, although mostly concentrated in the ventral part, which is closely
      linked to the yellow ligament. The interspinous ligament is well supplied by
      small blood vessels and sensory nerves, the latter particularly in its dorsal
      part and on its lateral surfaces. According to collected data, the structure of
      the interspinous ligaments reflects their function, i.e., the italic S-shaped
      course of the fibrous bundles represents an available reserve of length in a
      poorly elastic ligament.

PMID- 16974091
TI  - Reference models for mitral valve tissue engineering based on valve cell
      phenotype and extracellular matrix analysis.
AB  - The advance of mitral valve repair techniques through tissue engineering is
      impeded by the lack of information regarding the cellular and extracellular
      components of the mitral valve. The present study aims to expand our
      understanding of the mitral valve structure by analysing the synthesis of
      extracellular matrix (ECM) proteins and the expression of nitric oxide synthase
      (NOS). Valvular endothelial cells (VECs) and valvular interstitial cells (VICs)
      were isolated from porcine mitral valves. Immunochemical staining of ECM
      components, including type I, II, III, IV and V collagen, laminin, fibronectin,
      elastin and chondroitin sulphate (CS), was performed on both mitral valve tissue
      and cell cultures. Reverse transcription polymerase chain reaction and
      immunochemistry were used to analyse NOS expression in native valve and in
      culture. Both VECs and VICs synthesised the basement membrane components, laminin
      and type IV collagen both in vivo and in vitro, amongst other fibrous ECM
      proteins. Synthesis of type I collagen and CS was absent in VEC cultures. Each
      cell type had a characteristic profile of NOS expression. VECs synthesised
      endothelial NOS both in vivo and in vitro, with a minority of VICs expressing
      neuronal NOS in vitro. The present study reports newly recognised aspects of the
      mitral valve structure and the in vitro behaviour of mitral valve cell
      populations based on ECM synthesis and NOS expression. The presented profiles can
      be used as base tools for the generation of data necessary for the selection of
      ideal cell sources and for the design of appropriate scaffolds for the
      development of effective tissue-engineered mitral valves.

PMID- 16974092
TI  - Gene expression profiling of mouse embryonic stem cell progeny differentiated by
      Lumelsky's protocol.
AB  - Successful conversion of embryonic stem (ES) cells into insulin-producing cells
      has been reported by Lumelsky et al. (Science 2001;292:1389-1394); however, it
      remains controversial. In this study, we investigated the properties of ES cell
      progeny-induced differentiation according to Lumelsky's protocol by
      immunocytochemistry, oligonucleotide microarray and real-time RT-PCR. Insulin
      positive cells were observed at stages 3, 4 and 5. Microarray analysis
      demonstrated upregulation and appearance of some genes involved in pancreatic
      development but not beta-cell-specific functional genes in cells at stage 5.
      Similarly, real-time RT-PCR revealed that expression of beta-cell-specific
      functional genes such as islet amyloid polypeptide, insulin I and II was not
      increased in cells at stage 5. These results suggest that terminal
      differentiation of ES cell progeny toward functional pancreatic beta-cell is
      insufficient. This study also demonstrates the usefulness of multiple time-course
      expression profiles for validating differentiation fates of ES cell progeny.

PMID- 16974093
TI  - Cryopreservation of osteoblast-like cells: viability and differentiation with
      replacement of fetal bovine serum in vitro.
AB  - In reconstructive medicine, the clinical use of cryopreservation techniques
      depends on the absence of infectious agents such as prions. Therefore, we
      investigated the viability and differentiation of human osteoblast-like cells
      during replacement of fetal bovine serum in vitro. The aim of the present study
      is to replace the potentially infectious supplement fetal bovine serum during the
      cryopreservation procedure in order to perform future clinical trials. We used a
      cryopreservation technique with Me(2)SO for human osteoblast-like cells of iliac
      cancellous bone. In the cell culture of cryopreserved and fresh osteoblast-like
      cells, we substituted Dulbecco's modification of Eagle's medium (DMEM)/Ham's F12
      plus 1% penicillin/streptomycin with autologous serum, human serum albumin and
      Biseko for fetal bovine serum. For the fourth treatment group, we removed fetal
      bovine serum without replacing it. DMEM/Ham's F12 plus 1% penicillin/streptomycin
      with fetal bovine serum served as the control group. After 4, 7, 14 and 21 days
      of culture for the cryopreserved and noncryopreserved cells, we performed cell
      counting, a WST-1 test, ELISA for collagen type I, and osteocalcin. The activity
      of alkaline phosphatase was also measured. The best results were obtained for the
      group with autologous serum as a supplement after thawing, exceeding the other
      groups with regard to proliferation rate. Most viable cells were observed with no
      replacement before freezing and after thawing of the cells. With regard to
      differentiation, the cultures with autologous serum after thawing of the cells
      showed little concentration of the differentiation markers, probably due to early
      contact inhibition of the cells in vitro. With regard to effort and outcome, the
      most promising group for cryopreservation was the one with DMEM/Ham's F12 plus 1%
      penicillin/streptomycin alone before freezing, especially when osteoblast-like
      cells were cultured in medium with autologous serum after thawing. This is
      important, as this in vitro setting resembles the in vivo situation when
      cryopreserved bone is transplanted. These findings indicate that, for clinical
      purposes, fetal bovine serum can be removed for cryopreservation of iliac
      cancellous bone with minor loss of viability.

PMID- 16974094
TI  - Zona Pellucida Domain of ZPB1 controls specific binding of ZPB1 and ZPC in
      Japanese quail (Coturnix japonica).
AB  - The extracellular matrix surrounding avian oocytes, referred to as the
      perivitelline membrane (PL), exhibits a three-dimensional network of fibrils
      between granulosa cells and the oocyte. We previously reported that one of its
      components, ZPC, is synthesized in granulosa cells that are specifically
      incorporated into the PL; this incorporation might be mediated by a specific
      interaction with ZPB1, another PL constituent, which is synthesized in the liver.
      In order to extend our previous findings, we established an expression system for
      quail ZPB1 using a mammalian cell line, and several ZPB1 mutants lacking the zona
      pellucida (ZP) domain or the glutamine-rich repeat region were produced. Western
      blot analysis of the immunoprecipitated materials with anti-ZPC antiserum
      indicated that ZPB1 was coimmunoprecipitated with the antiserum in the presence
      of ZPC. Ligand blotting also revealed the specific binding of ZPC and ZPB1 and
      indicated that the binding of these two components might be mediated via an ionic
      interaction. An analysis using recombinant ZPB1 demonstrated that the ZPB1
      lacking the ZP domain did not bind to ZPC, whereas the mutant missing the
      glutamine-rich repeat region retained its capacity for binding. Furthermore,
      although the ZPB1 lacking the N-terminal half of the ZP domain was able to bind
      to ZPC, the deletion of the C-terminal half completely abolished ZPB1 binding to
      ZPC. These results suggested that the C-terminal half of the ZP domain of ZPB1
      contains a binding site for ZPC, and that it appears to be involved in insoluble
      PL fibril formation in the quail ovary.

PMID- 16974095
TI  - Do lesions involving the cortical cholinergic pathways help or hinder efficacy of
      donepezil in patients with Alzheimer's disease?
AB  - AIMS: To investigate the influences of vascular lesions detected by MRI, lesions
      involving the cortical cholinergic pathways and hippocampal thickness on
      therapeutic responsiveness to donepezil in patients with Alzheimer's disease
      (AD). METHODS: The study cohort contained 67 patients with probable AD. We used
      the revised Hasegawa Dementia Rating (HDS-R) and the Clock Drawing Test (CDT) to
      evaluate drug efficacy for 24 months. The Cholinergic Pathways Hyperintensities
      Scale (CHIPS), a newly developed visual scale, was used to semiquantify lesions
      on the cholinergic pathways. RESULTS: Over the 24-month period, the results of
      the CDT showed more apparent and constant association with white matter
      hyperintensities (WMH) and lesions on the cholinergic pathways than the HDS-R.
      WMH may enhance, while lesions on the cholinergic pathways may attenuate
      sensitivity to donepezil treatment when judged by the CDT. No apparent
      association between the thicknesses of hippocampi with baseline cognition or
      therapeutic responsiveness to donepezil was found. CONCLUSION: Donepezil may be
      more efficacious when further executive dysfunction caused by WMH is added to AD
      dementia and less so when cholinergic reserves are further impinged upon by
      lesions involving the cortical cholinergic pathways.

PMID- 16974097
TI  - An original approach to aging: an appreciation of Fritz Verzar's contribution in
      the light of the last 50 years of gerontological facts and thinking.
AB  - The motivation of this review is the 120th anniversary of the birth of Fritz
      Verzar, founder of experimental gerontology. His major contributions to aging
      research are shortly reviewed and re-evaluated in the light of modern
      gerontological research. Verzar undertook aging research after his retirement
      from the Chair of Physiology at the Medical Faculty of Basel. His first
      experiments on aging of the rat tail tendon revealed an important mechanism of
      aging: an exponential increase of cross-linking of collagen fibres. This
      observation, correctly interpreted by Verzar as a new age-dependent mechanism,
      was shown later to be attributed to the Maillard reaction, the non-enzymatic
      glycosylation of protein (and nucleotide bases) amino groups followed by
      evolution of the reaction to advanced glycation end products (AGEs) involved in a
      number of harmful reactions. Many of these reactions were shown to be mediated by
      receptors recognizing AGE products (RAGEs). This was the first example of a post
      synthetic (post-translational) reaction involved in the aging of biological
      macromolecules, especially those of the extracellular matrix. Verzar extended the
      research activity of his team to several other aspects of aging research, such as
      loss of muscular strength, nutritional requirements at high altitude, cell loss
      with aging, and ultrastructural studies, and started also the first longitudinal
      clinical study of aging in a Basel population. Modern gerontological research
      confirmed and extended Verzar's observations. His work on collagen cross-linking
      by glycation became of paramount importance in recent times because of the rapid
      increase of diabetes type II, combined with the metabolic syndrome, one of the
      major pathologies of modern times.

PMID- 16974098
TI  - Estimation of height and body mass index from demi-span in elderly individuals.
AB  - BACKGROUND: Obtaining accurate height and, consequently, body mass index (BMI)
      measurements in elderly subjects can be difficult due to changes in posture and
      loss of height during ageing. Measurements of other body segments can be used as
      an alternative to estimate standing height, but population- and age-specific
      equations are necessary. OBJECTIVE: Our objectives were to validate existing
      equations, to develop new simple equations to predict height in an elderly
      Spanish population and to assess the accuracy of the BMI calculated by estimated
      height from the new equations. METHODS: We measured height and demi-span in a
      representative sample of 592 individuals, 271 men and 321 women, 65 years and
      older (mean +/- SD, 73.8 +/- 6.3 years). We suggested equations to predict height
      from demi-span by multiple regression analyses and performed an agreement
      analysis between measured and estimated indices. RESULTS: Height estimated from
      demi-span correlated significantly (p < 0.001) with measured height (men: r =
      0.708, women: r = 0.625). The best prediction equations were as follows: men,
      height (in cm) = 77.821 + (1.132 x demi-span in cm) + (-0.215 x 5-year age
      category); women: height (in cm) = 88.854 + (0.899 x demi-span in cm) + (-0.692 x
      5-year age category). No significant differences between the mean values of
      estimated and measured heights were found for men (-0.03 +/- 4.6 cm) or women (
      0.02 +/- 4.1 cm). The BMI derived from measured height did not differ
      significantly from the BMI derived from estimated height either. CONCLUSION:
      Predicted height values from equations based on demi-span and age may be
      acceptable surrogates to derive accurate nutritional indices such as the BMI,
      particularly in elderly populations, where height may be difficult to measure
      accurately.

PMID- 16974099
TI  - Cerebral blood flow responses to severe orthostatic stress in fit and unfit young
      and older adults.
AB  - BACKGROUND: Animal models suggest that aging negatively affects the cerebral
      blood flow (CBF) response to a hypotensive challenge while research with humans
      suggests that chronic physical activity may positively affect age-associated
      alterations in CBF. The extent to which chronic exercise affects the CBF
      responses to orthostatic stress in older subjects is unknown. OBJECTIVES: The
      purpose of this study was to determine the extent to which differences in age and
      cardiovascular fitness, reflective of differences in chronic exercise training,
      affect cerebral blood flow responses to severe orthostatic stress. METHODS:
      Subjects were divided into four groups: old fit (OF; 72 +/- 2 year-olds; 38.7 +/-
      1.6 ml.kg(-1).min(-1)), old unfit (OU; 71 +/- 1 year-olds; 27.7 +/- 2.9 ml.kg(
      1).min(-1)), young fit (YF; 23 +/- 0.5 year-olds; 56.1 +/- 1.8 ml.kg(-1).min(-1))
      and young unfit (YU; 23 +/- 1 year-olds; 41.1 +/- 1.6 ml.kg(-1).min(-1)). Fitness
      was quantified with maximal graded exercise testing. Middle cerebral artery blood
      flow velocity (CBF velocity; transcranial Doppler) responses to graded
      orthostatic stress (lower body negative pressure) to presyncope were assessed.
      RESULTS: Orthostatic tolerance did not differ between groups (p = 0.633). The
      groups differed in fitness (YF >YU = OF >OU; p < 0.001) but not in either resting
      CBF velocity (p = 0.364) or pulsatility index (PI; p = 0.251). CBF velocity
      decreased below rest in the last completed stage of submaximal LBNP (p < 0.001)
      but did not differ between groups (p = 0.182). PI did not change with submaximal
      LBNP within groups. At presyncope, mean CBF velocity decreased below that of the
      last completed stage of LBNP in all groups (p < 0.001) while the PI increased in
      the young fit group only (p < 0.001). CONCLUSION: Marked differences in age and
      fitness did not affect cerebral blood flow responses to severe orthostatic
      stress. While severe orthostatic stress can compromise CBF velocity in all age
      groups, older adults appear to autoregulate CBF as well as much younger subjects.

PMID- 16974100
TI  - Introduction. Back to nurture: cross-cultural research as a paradigm for
      understanding bio-cultural dynamics of cognitive ageing.
AB  - BACKGROUND: One of the earliest and most persistent inquiries in developmental
      psychology is that of the relative contributions of nature and nurture to human
      ontogeny. One way of studying this distinction is by doing cross-cultural
      studies, in which culture provides a powerful way to operationalize the influence
      of nurture. OBJECTIVE: The purpose is to provide some background to the emergence
      of the field of cross-cultural gerontological research, as a prelude to the
      special series of papers on cognitive ageing and culture from the laboratory of
      Park and Nisbett and their colleagues. METHODS: A qualitative review of
      theoretical notions about cross-cultural differences provides an introduction and
      orientation to papers dealing with aspects of cognitive ageing, including picture
      naming specificity, source memory, use of categorical information in free recall,
      and perceptions of stereotypes of older and younger adults. RESULTS: Most of the
      research on cognitive ageing has focused on Western cultures and has assumed
      universality in the operation of the cognitive system. If culture makes a
      difference, a plausible hypothesis might be that, with ageing, any effects of
      culture on cognitive processes would become more apparent, due to older adults'
      increased exposure to their culture, and that these might be limited to the
      pragmatics of intelligence or crystallized abilities. The papers presented
      demonstrate that for some cognitive processes, i.e., source memory and free
      recall, cultural invariance, or universality of cognitive ageing, was observed.
      Further, stereotypes of both cultures shifted with advancing age from positive to
      increasingly negative views for mental and physical domains. A modest interaction
      of age and culture was observed in social and emotional domains, where
      stereotypes were relatively neutral, except for a small positive bias among the
      young Chinese participants for both older and younger adults. Marked cultural
      differences were seen in naming specificity and in the use of categories to
      structure the recall process. CONCLUSIONS: Claims have been made about universals
      of cognitive function, particularly for basic cognitive processes. These results
      challenge that view. Cross-cultural research has begun to reshape the way we
      think about cognitive ageing.

PMID- 16974101
TI  - Pictorial naming specificity across ages and cultures: a latent class analysis of
      picture norms for younger and older Americans and Chinese.
AB  - BACKGROUND: Cognitive aging research, as well as cross-cultural research, often
      relies on pictorial stimuli to address how perceptions of common objects vary by
      population group. OBJECTIVE: We investigate naming specificity--the degree of
      detail elicited for object labels - across age (younger-older) and culture
      (American-Chinese). METHODS: Using latent class analysis techniques, we
      segregated picture-item responses into multiple specificity levels. The analysis
      was conducted for 260 pictures, across four groups of younger (aged 17-25 years)
      and older (aged 59-76 years) adults in the US and mainland China. RESULTS:
      Overall, three naming specificity classes were supported. Age differences were
      modest compared to those across culture. In particular, Chinese groups showed far
      greater variation, naming more items both with high and with low specificity than
      age-matched American counterparts. Our results differed from prior studies using
      familiarity and latency measures. Moreover, approximately 28% of commonly-used
      picture items differed across all four groups. CONCLUSION: These results
      highlight the need to select appropriate pictorial stimuli for studies involving
      populations diverse in age and cultural background.

PMID- 16974102
TI  - Source memory, aging and culture.
AB  - BACKGROUND: The present study investigates the possibility that culture affects
      age differences in context memory. There is evidence that East-Asians process
      scenes more holistically and show better context memory than Americans.
      OBJECTIVE: We examined evidence for differences in binding source to context in
      young and old Americans and native Chinese. We hypothesized that age effects on
      source memory could be mitigated due to these cultural differences in processing
      style. METHODS: During incidental encoding, younger and older Chinese and
      Americans watched a video with statements spoken by four distinct speakers. After
      a brief interval, participants identified source (experiment 1) or item and
      source (experiment 2). RESULTS: We observed substantial age-related deficits in
      source memory in both cultures but little evidence for cultural differences in
      source or item memory. CONCLUSION: Basic source memory processes operate
      similarly across culture and age. The source of holistic processing differences
      observed between cultures may occur in cognitive operations that are more highly
      bound to a social context.

PMID- 16974103
TI  - Categorical organization in free recall across culture and age.
AB  - BACKGROUND: Cross-cultural differences in cognition suggest that Westerners use
      categories more than Easterners, but these differences have only been
      investigated in young adults. OBJECTIVE: The contributions of cognitive resource
      and the extent of cultural exposure are explored for free recall by investigating
      cross-cultural differences in categorical organization in younger and older
      adults. Cultural differences in the use of categories should be larger for
      elderly than young because categorization is a well-practiced strategy for
      Westerners, but age-related cognitive resource limitations may make the strategy
      difficult for elderly Easterners to implement. Therefore, we expect that cultural
      differences in categorization will be magnified in elderly adults relative to
      younger adults, with Americans categorizing more than Chinese. METHODS: Across
      two studies, 112 young and 112 elderly drawn from two cultures (American and
      Chinese) encoded words presented in their native language. One word list
      contained categorically-unrelated words and the other, categorically-related
      words; both lists were presented in the participants' native language. In
      experiment 1, the words were strong category associates, and in experiment 2, the
      words were weak category associates. Participants recalled all the words they
      could remember, and the number of words recalled and degree of clustering by
      category were analyzed. RESULTS: As predicted, cultural differences emerged for
      the elderly, with East-Asians using categories less than Americans during recall
      of highly-associated category exemplars (experiment 1). For recall of low
      associate exemplars, East-Asians overall categorized less than Americans
      (experiment 2). Surprisingly, these differences in the use of categories did not
      lead to cultural differences in the number of words recalled. The expected
      effects of age were apparent with elderly recalling less than young, but in
      contrast to previous studies, elderly also categorized less than young.
      CONCLUSION: These studies provide support for the notion that cultural
      differences in categorical organization are larger for elderly adults than young,
      although culture did not impact the amount recalled. These data suggest that
      culture and age interact to influence cognition.

PMID- 16974104
TI  - Age-related stereotypes: a comparison of American and Chinese cultures.
AB  - BACKGROUND: It is commonly assumed that age-related stereotypes are more positive
      in East Asian cultures compared to Western cultures. However, research conducted
      in Western cultures has demonstrated that age-related stereotypes are
      multidimensional and their valence is content-dependent. OBJECTIVE: In this study
      we investigated stereotypes about young and old adults, held by both young and
      old in the US and in China by focusing on the valence of age stereotypes across
      two content domains: social/emotional and mental/physical. The goal was to
      identify whether there were any cultural differences in age-related stereotypes
      in Chinese and American cultures. METHODS: Both young and old Chinese and
      American participants were asked to describe typical young and typical old
      people. All responses were then coded for valence (positive/negative/neutral) and
      for content (mental/physical, social/emotional, other). Descriptors about young
      and old people were initially analyzed separately; then data were integrated to
      examine group tendencies to be more positive or negative for each target age
      group. RESULTS: In both cultures, stereotypes reflected a shift from more
      positive to increasingly negative views of mental and physical traits as a
      function of aging. In social and emotional domains, stereotypes regarding old and
      young adults were relatively neutral, except for a small positive bias found
      among the young Chinese adults for both target age groups. CONCLUSION: Our
      results indicate that age-related beliefs regarding typical older adults are
      similar across East-Asian and Western cultures and that a global positive bias
      for old age in East-Asia is absent.

PMID- 16974105
TI  - Oral clonidine provocative test in the diagnosis of growth hormone deficiency in
      childhood: should we make the timing uniform?
AB  - INTRODUCTION: Oral clonidine is one of the most frequent drugs used for the
      diagnosis of growth hormone deficiency (GHD), but the duration of the test,
      depending on which European centres use it, is not uniform and can vary from 120
      to 150 min or even 180 min. SUBJECTS AND METHODS: To standardize this test,
      evaluating the possibility to shorten it to 90 min, we investigated the response
      of GH to the oral clonidine test in 291 children evaluated for short stature
      (height <-2 SD). Of these, 164 were diagnosed as idiopathic short stature (ISS)
      and 127 as GHD. In these patients, we calculated: (1) the frequency distribution
      of the GH peaks to clonidine in GHD and in ISS at various times; (2) the
      percentage of GH peaks to clonidine before and after 90 min in all and in ISS
      children; (3) the percentage of the first GH value >or=10 ng/ml before 90 min and
      after 90 min in ISS. RESULTS: GH peak distribution varied between 30 and 180 min,
      even though the vast majority of peaks occurred between 30 and 60 min. There was
      no significant difference (p > 0.05) in the peak distribution between ISS and GHD
      children. The percentages of GH peaks within 90 min were 92.1% in all children
      and 95.7% in ISS. If considering the first value of GH >or=10 ng/ml this last
      percentage reaches 96.3%. CONCLUSION: Our study suggests that the oral clonidine
      test can be administered for only 90 min without significantly changing its
      validity. This test should be standardized at 90 min in European protocols just
      as in those currently used in the USA in order to reduce the discomfort of
      patients and the cost of this diagnostic procedure.

PMID- 16974106
TI  - Unexpected peripheral markers of thyroid function in a patient with a novel
      mutation of the MCT8 thyroid hormone transporter gene.
AB  - The specific thyroid hormone transporter, MCT8, located on the X chromosome, has
      led to the identification a novel syndrome. The objective is to relate phenotype
      with several tissue-specific thyroid functions. A 1-year-old boy, who had severe
      psychological damage and low serum T4, had received l-T4 for 3 months. At
      admission, body length was normal but weight was low. Off therapy, serum TSH was
      mildly elevated, serum T4 and free T4 were low, and serum T3 and free T3 were
      high. Direct sequencing of the MCT8 gene revealed a single nucleotide change that
      resulted in a novel nonsense mutation at codon 261 (Q261X) in exon 3. Since serum
      T3 was high, peripheral markers of hyperthyroidism were looked for. Bone age was
      advanced, despite the presence of malnutrition and low T4. Serum SHBG, a marker
      of thyroid hormone action in liver, was markedly elevated. Markers of skeletal
      muscle catabolism, ammonemia and lactic acid, were found to be elevated. The
      phenotype of MCT 8 mutation might be explained by differences in the entry of
      thyroid hormones into different cells. In the presence of an inactive MCT8
      transporter, the high blood T3 levels might not be enough to prevent brain damage
      early in life, while they seem to be able to induce a postnatal state of
      peripheral hyperthyroidism in other tissues, such as liver, bone and skeletal
      muscle.

PMID- 16974107
TI  - An inhibin B and estrogen-secreting adrenocortical carcinoma leading to selective
      FSH suppression.
AB  - OBJECTIVE: Hormone-secreting adrenocortical tumors are frequently associated with
      endocrine syndromes. We describe a 30-year-old man who had abdominal pain, a
      nodule in the right breast and loss of libido. Abdominal magnetic resonance
      imaging revealed a very large tumor in the right adrenal gland. METHODS: Hormonal
      profile disclosed increased levels of estradiol and slightly low testosterone
      levels. The basal and stimulated LH levels were normal, whereas basal and
      stimulated FSH levels were totally suppressed. Cortisol and adrenal androgen
      levels were normal. The unusual finding of selective FSH suppression suggested
      secretion of inhibin B by the adrenocortical tumor. A very high level of serum
      inhibin B (405 pg/ml) was demonstrated by ELISA assay. Right adrenalectomy and
      nephrectomy were performed and the tumor was classified as a malignant tumor
      (Weiss score: 7.0) and unilateral mastectomy disclosed a lipoma. RESULTS: One
      week after surgery, a GnRH-stimulation test disclosed normal basal and stimulated
      FSH levels and low levels of inhibin B and estradiol. Immunohistochemical
      analysis with anti-B-inhibin antibody revealed intense staining in the
      adrenocortical tumor cells. One month after surgery, an abdominal magnetic
      resonance imaging revealed a local recurrence of the tumor and a second surgery
      was performed with partial resection of the tumor and the patient died 1 year
      after the first surgery. CONCLUSION: We herein report the first inhibin B and
      estradiol-secreting adrenocortical carcinoma. The unusual selective inhibition of
      FSH secretion should be considered a valuable hormonal finding for the diagnosis
      of inhibin B-secreting adrenocortical tumors.

PMID- 16974108
TI  - Impact on health-related quality of life and perceived burden of informal
      caregivers of individuals with Alzheimer's disease.
AB  - This study assessed the impact on health-related quality of life (HRQL) and the
      perceived burden of informal caregivers of individuals with Alzheimer's disease
      (AD) on the Canary Islands (Spain). We utilized a multicenter, cross-sectional
      design, based on questionnaire responses of 237 informal caregivers of AD
      patients. Patients were classified according to the degree of severity utilizing
      the Clinical Dementia Rating Scale. Sociodemographic, HRQL (EQ-5D) and functional
      dependency data were gathered together with the degree of caregiver burden.
      Caregivers had a higher frequency of problems than did the general population for
      every EQ-5D dimension. Caregivers' HRQL was inversely associated with the subject
      dependency level and caregiver age. HRQL was higher for more educated caregivers.
      Variables with a negative and/or significant effect on caregivers' HRQL were high
      feelings of burden, more committed time to care, and older age. The caregiver
      burden quantified by the Zarit scale showed 83.3% of caregivers with a high level
      of burden.

PMID- 16974109
TI  - Chronic psychological distress and risk of Alzheimer's disease in old age.
AB  - Clinical and pathological data from the Rush Memory and Aging Project were used
      to test the hypothesis that distress proneness is associated with increased risk
      of Alzheimer's disease (AD). More than 600 older persons without dementia
      completed a 6-item measure of neuroticism, a stable indicator of proneness to
      psychological distress. At annual intervals thereafter, they underwent uniform
      evaluations that included clinical classification of AD and administration of 18
      cognitive tests. Those who died underwent brain autopsy from which composite
      measures of AD pathology were derived. During a mean of about 3 years of follow
      up, 55 people were clinically diagnosed with AD. In analyses that controlled for
      age, sex, and education, persons with a high level of distress proneness (score =
      24, 90th percentile) were 2.7 times more likely to develop AD than those not
      prone to distress (score = 6, 10th percentile). Adjustment for depressive
      symptomatology or frequency of cognitive, social, and physical activity did not
      substantially change this effect. Distress proneness was also associated with
      more rapid cognitive decline. Among 45 participants who died and underwent brain
      autopsy, distress proneness was unrelated to diverse measures of AD pathology and
      was inversely related to cognition after controlling for AD pathology. The
      results support the hypothesis that distress proneness is associated with
      increased risk of dementia and suggest that neurobiologic mechanisms other than
      AD pathology may underlie the association.

PMID- 16974110
TI  - In vivo effects of mitoxantrone on the production of pro- and anti-inflammatory
      cytokines by peripheral blood mononuclear cells of secondary progressive multiple
      sclerosis patients.
AB  - OBJECTIVE: Mitoxantrone is an antineoplastic agent also used for the treatment of
      multiple sclerosis (MS). However, despite its efficacy, few data are available on
      its mechanism of action. The current study was designed to evaluate the short
      term (1 month) and long-term (12 months) in vivo effects of mitoxantrone on pro-
      and anti-inflammatory cytokine production by the peripheral blood mononuclear
      cells (PBMC) of secondary progressive MS patients. METHODS: Eighteen patients
      with secondary progressive MS underwent mitoxantrone therapy (at a dose of 12
      mg/m(2) once every 3 months) over a 1-year period. Blood samples were obtained at
      baseline, after 1 month and after 12 months of treatment. The production of
      cytokines in the PBMC was measured by enzyme-linked immunosorbent assay. RESULTS:
      There were no significant effects of mitoxantrone on proinflammatory cytokines
      [interleukin (IL) 6 and IL-12p40] and anti-inflammatory cytokines (IL-10 and
      transforming growth factor-beta) in our patients. Patients who showed no signs of
      therapeutic response were characterized by a higher basal PBMC production of IL-6
      compared with that of the responding patients (p < 0.05) and mitoxantrone reduced
      this production after 12 months of treatment (p < 0.05). In the responding
      patients, IL-10 was significantly increased by mitoxantrone after 12 months of
      treatment (p < 0.05). CONCLUSION: These findings provide additional information
      useful in the selection of the patient population suitable for mitoxantrone
      treatment and suggest that most probably the therapeutic action of mitoxantrone
      in MS is not entirely mediated by its immunosuppressant effects.

PMID- 16974111
TI  - CD95 system counter attack and prognostic impact.

PMID- 16974112
TI  - Expression of Fas ligand (CD95L) in primary malignant melanoma and melanoma
      metastases is associated with overall survival.
AB  - BACKGROUND: There is increasing evidence that the Fas/Fas ligand (FasL) system is
      involved in tumor-mediated immune suppression. The purpose of this study was to
      investigate the effect of Fas (CD95) as well as FasL (CD95L) expression in
      primary malignant melanoma and melanoma metastases on overall survival (OS).
      PATIENTS AND METHODS: 19 patients with metastatic malignant melanoma who were
      treated with different dacarbazine (DTIC)-based chemotherapy regimens were
      included in this study. From each patient, primary melanoma biopsies and biopsies
      from metastases were histologically evaluated. Immunohistology was performed with
      antibodies to Fas/CD95 and FasL/CD95L. Differences in OS were plotted using the
      Kaplan-Meier method and compared by the log rank test. RESULTS: Fas/CD95 and
      FasL/CD95L expression was detected in 73.7 and 63.2% of primary melanomas,
      respectively. In metastases, expression of both Fas/CD95 (63.2%) and FasL/CD95L
      (47.4%) was markedly decreased. Presence of FasL/ CD95L expression in primary
      melanoma resulted in significantly (p = 0.024) prolonged OS compared with
      FasL/CD95L-negative high-risk primary melanomas. In contrast, loss of FasL/CD95L
      expression in melanoma metastases resected before chemotherapy was associated
      with significantly prolonged median survival (p = 0.0139). CONCLUSION: Presence
      of FasL/CD95L expression in primary malignant melanoma and the loss of FasL/
      CD95L expression in metastases seem to be positive prognostic factors.

PMID- 16974113
TI  - Growth arrest and apoptosis of the human hepatocellular carcinoma cell line BEL
      7402 induced by melittin.
AB  - OBJECTIVE: The aim of this study was to investigate the cellular effects of
      melittin on the growth and apoptosis of human hepatocellular carcinoma (HCC)
      cells and to provide the molecular mechanism for potential application of a
      recombinant adenovirus carrying the melittin gene (Ad-rAFP-Mel) in the treatment
      of liver cancer. METHODS: Human HCC cells (BEL-7402) were infected with Ad
      rAFPMel at different times. In vitro cell growth was determined by MTT assay.
      Cellular apoptosis was evaluated quantitatively and qualitatively by phase
      contrast microscopy, transmission electron microscopy, DNA ladder
      electrophoresis, TUNEL staining and flow cytometry. RESULTS: Ad-rAFP-Mel
      infection had an inhibitory effect on the proliferation of BEL-7402 cells. The
      morphological changes of apoptosis were confirmed by microscopy and DNA
      electrophoresis. The ultrastructural characteristics of apoptotic cells, such as
      chromatin condensation and nuclear fragmentation, were also observed by electron
      microscopy in the Ad-rAFP-Mel-infected cells. Ad-rAFPMel infection markedly
      induced cellular apoptosis, and Fas expression on Bel-7402 cells infected by Ad
      rAFPMel was up-regulated. CONCLUSION: The fact that melittin can induce apoptosis
      of the HCC cell line BEL-7402 leads us to consider adenovirus-mediated delivery
      of melittin as a promising approach for the treatment of HCC. However, the
      underlying mechanism needs to be further investigated.

PMID- 16974114
TI  - Intraoperative touch imprint cytological analysis of sentinel lymph nodes for the
      presence of metastases in breast cancer.
AB  - BACKGROUND: Imprint cytology may provide a fast and accurate method for
      intraoperative screening of sentinel lymph nodes, so a decision can be made
      regarding whether to perform axillary clearance during primary surgery. If the
      findings are negative, in many cases axillary dissection can be omitted. PATIENTS
      AND METHODS: 128 sentinel nodes from a cohort of 87 patients that had been
      identified using technetium-99m nanocolloid as a radioactive tracer and Patent
      blue dye were dissected for rapid Diff-Quick stained touch preparations.
      Intraoperative evaluation of sentinel node status by imprint cytology was
      correlated with histopathological results of permanent sections. Tumor-negative
      nodes in routine paraffin sections were further investigated with the employment
      of an anti-cytokeratin antibody. RESULTS: 36 of all sentinel nodes harbored
      metastases in the paraffin sections, of which 32 were identified by imprint
      cytology (sensitivity 88.8%). 3 sentinel nodes were positive by imprint cytology
      and negative by histopathology of the paraffin sections. Comparison of the
      results of the touch preparations with the final histopathology (hematoxylin
      eosin and anticytokeratin antibody stains) demonstrated a sensitivity of 83.3%
      and a negative predictive value of 92.5%. The specificity and positive predictive
      value were 100% each. CONCLUSIONS: Touch imprint cytology is potentially useful
      for intraoperative evaluation of sentinel lymph nodes in breast cancer patients.

PMID- 16974115
TI  - Expression of Bcl-2 and Ki-67 in tamoxifen-associated endometrial polyps:
      comparison with postmenopausal polyps.
AB  - BACKGROUND: The aim of this study was to evaluate the expression of Bcl-2 and Ki
      67 in tamoxifen (TAM)-associated endometrial polyps and postmenopausal polyps.
      MATERIAL AND METHODS: For this purpose, a retrospective analysis of paraffin
      embedded specimens was carried out. Polyps of 20 postmenopausal and 14 TAM
      treated patients, 11 simple endometrial hyperplasia, 10 atypical complex
      endometrial hyperplasia and 8 endometrial adenocarcinoma specimens were included
      in the study. Hematoxylin/eosin-stained sections were evaluated.
      Immunohistochemical staining was performed to investigate the expression of Bcl-2
      protein and the Ki-67 proliferation index. RESULTS: There was no statistically
      significant difference between the 5 groups with regard to Bcl- 2 staining (p >
      0.05). However, Bcl-2 expression in TAM-associated polyps was higher (86%) than
      in the postmenopausal control group (80%). Positive Ki-67 was highest in the
      endometrial adenocarcinoma specimens, followed by the atypical complex
      endometrial hyperplasia group (p < 0.0001). Compared to these 2 groups, Ki- 67
      expression was lower in TAM-associated polyps, but Ki-67 indexes were
      significantly higher in the TAM-associated group than in the control group (p <
      0.0001). CONCLUSION: Since TAM-associated polyps tend to have higher
      proliferation indexes and Ki-67 ratios than control groups, we suggest that they
      are likely to have a higher malignant potential.

PMID- 16974116
TI  - Long-lasting remission of pulmonary metastases of renal cell cancer under IFN
      beta therapy in a patient with multiple sclerosis.
AB  - BACKGROUND: Immunomodulary therapy based on interferon (IFN)-a has been shown to
      be effective in a subset of patients with advanced renal cell carcinoma (RCC).
      IFN-Beta has occasionally been reported to induce remissions in RCC, but is well
      established in the treatment of multiple sclerosis (MS). There is an ongoing
      debate whether hyperactivation of the immune system may convey protection against
      the development of cancer in MS patients. PATIENTS AND METHODS: A 54-year-old
      female MS patient underwent tumor nephrectomy for RCC in 1994. 1 year later,
      several bilateral pulmonary metastases were documented by computed tomography and
      were histologically confirmed thereafter. Therapy with IFN-Beta was started.
      RESULTS: Soon after initiation of IFN-Beta treatment, the patient achieved an
      almost complete remission which is still ongoing after 10 years of IFN-Beta
      therapy. CONCLUSION: To our knowledge, this is the longest remission under IFN
      Beta treatment ever reported in an RCC patient. We conclude that IFN-Beta should
      be particularly considered as a therapeutic option in the rare occasion of
      metastatic RCC in patients with MS.

PMID- 16974117
TI  - Oncocytic carcinoma of the parotid gland.
AB  - BACKGROUND: Oncocytic carcinoma is a rare tumor of major salivary glands. Despite
      being described 5 decades ago, not much is known about these rare tumors.
      Histochemical or electron microscopic confirmation of the oncocytic nature of the
      tumor cell is needed for differential diagnosis. The main treatment modality is
      surgery with or without adjuvant radiotherapy. Malignant oncocytomas have the
      potential risk of developing distant metastases and demand long term follow-up
      after therapy. CASE REPORT: A 58-year old man presented with a recurrent mass in
      the left parotid gland with a prior diagnosis of monomorphic adenoma in the same
      localization which had been treated by tumor excision in July 2002. Left
      superficial parotidectomy followed by radiotherapy into tumor bed and upper neck
      were carried out in September 2004. To date, he has had no evidence of recurrence
      for 14 months. CONCLUSION: For an accurate approach in the management of
      patients, oncocytic adenocarcinoma should be considered in the differential
      diagnosis of lesions of the parotid gland, most of which are benign.

PMID- 16974118
TI  - Targeted approaches for treating advanced clear cell renal carcinoma.
AB  - The mainstay of any curative treatment in renal cell carcinoma (RCC) is surgery.
      In the case of metastatic disease at presentation, a radical nephrectomy is
      recommended to good performance status patients prior to the start of cytokine
      treatment. Interferon (IFN)-a offers in a small but significant percentage of
      patients advantage in overall survival. Interleukin (IL)-2-based therapy gives
      similar survival rates. To date, hormonal therapy and chemotherapy do not have a
      proven impact on survival. Recent insights demonstrate that the majority of clear
      cell RCC harbor abnormalities of the von Hippel-Lindau (VHL) gene. This gene
      plays a key role in the stimulation of angiogenesis by vascular endothelial
      growth factor (VEGF) in this highly vascularized tumor. This opens interesting
      new treatment strategies including blockade of VEGF with the monoclonal antibody
      bevacizumab (Avastin) and inhibition of VEGF receptor tyrosine kinases with small
      oral molecules such as sunitinib (SU11248, Sutent) or PTK787. Likewise,
      inhibition of the Raf kinase pathway with oral sorafenib (Bay 43-9006, Nexavar)
      or inhibition of the mTOR pathway with intravenous CCI-779 are under
      investigation. Preliminary clinical results with all these compounds are
      promising, and the results of ongoing first-line phase III studies will become
      available in the next years.

PMID- 16974119
TI  - [Pillnitz interdisciplinary discussion--summary].

PMID- 16974120
TI  - [Diagnosis of non-small-cell lung carcinoma (NSCLC)].

PMID- 16974121
TI  - [Surgery and adjuvant therapy in non-small-cell lung carcinoma (NSCLC). (stage I
      through operable stage IIIA)].

PMID- 16974122
TI  - [Therapy in non-small-cell lung carcinoma (NSCLC) in local advanced stage
      (inoperable IIIA/IIIB)].

PMID- 16974123
TI  - [Therapy for non-small-cell lung carcinoma (NSCLC) in stage IV].

PMID- 16974124
TI  - [Concept of quality assurance in the management of lung carcinoma].

PMID- 16974125
TI  - [New perspectives in the management of non-small-cell lung carcinoma (NSCLC)].

PMID- 16974126
TI  - Roller culture of free-floating retinal slices: a new system of organotypic
      cultures of adult rat retina.
AB  - No experimental system exists to date for the in vitro study of retinal ganglion
      cell populations in a three-dimensional organotypic tissue environment. Here, we
      describe such a novel method for roller cultivation of adult retinas. Retinas of
      adult (1-3 months old) rats were cut into rectangular slices of approximately 1
      mm(2). Free-floating slices were cultured on a horizontal rotating roller drum
      (50-60 rpm) in a dry incubator at 36.5 degrees C. During the first days of
      cultivation, primary flat retinal slices changed their configuration and
      transformed into ball-shaped tissue spheres (retinal bodies). Histological and
      immunocytochemical studies showed that the outer wall of the retinal bodies was
      formed by cell and fibre layers typical of mature retina with photoreceptors
      located on the outside. Initially, retinal bodies contained an inner cavity which
      later was completely obliterated and filled with glial cells, sprouting nerve
      fibres, and vascular structures. This culture system was further developed into a
      robust model of glutamate-induced neurotoxicity. Using a novel culture method of
      adult rat retina, preservation of the three-dimensional organotypic retinal
      cytoarchitecture was achieved, including survival of neurons in the ganglion cell
      layer and sprouting of nerve fibres of the axotomized retinal ganglion cells.
      This novel culture model promises to facilitate studies of retinal physiology and
      pathology.

PMID- 16974127
TI  - Effect of topical nipradilol on retinal microvascular leukocyte adhesion in
      diabetic rats.
AB  - BACKGROUND: Retinal leukostasis plays an important role in the pathogenesis of
      diabetic retinopathy. OBJECTIVES: We studied the effects of nipradilol, a topical
      antiglaucoma alphabeta-blocker and nitric oxide donor, on the retinal vascular
      leukocyte adhesion of rats with diabetes. METHODS: Diabetes was induced in seven
      Brown-Norway rats by one intravenous injection (65 mg/kg) of streptozotocin and
      confirmed by blood glucose levels >350 mg/dl 48 h after the injection. Nipradilol
      solution was instilled in the right eye and nipradilol-free base solution in the
      left eye for 3 weeks, after which the retinal microcirculation was evaluated by
      acridine orange leukocyte digital fluorography using laser scanning
      ophthalmoscopy. Leukocytes trapped in the retina were counted around the optic
      disc in a 5-disc-diameter area and compared between the right and the left eye.
      RESULTS: The mean retinal leukostasis count in the nipradilol-treated eyes (19 +/
      15 cells) was significantly lower than in the untreated eyes (49 +/- 19 cells; p
      < 0.0008). The diameter of the retinal artery in the eyes treated with nipradilol
      significantly increased (111 +/- 13.5%) compared with untreated eyes (p < 0.03).
      CONCLUSIONS: Topical nipradilol significantly reduced retinal leukostasis in the
      retinal microcirculation in diabetic rats and may be a prophylactic agent for
      early diabetic retinopathy through its nitric oxide donor effects on the
      microcirculation.

PMID- 16974128
TI  - Quantitative analysis of chondroitin sulfate in tear fluids following laser in
      situ keratomileusis.
AB  - PURPOSE: To report chondroitin sulfate (CS) concentrations in tear fluid
      following laser in situ keratomileusis (LASIK). METHODS: Fourteen eyes that
      underwent LASIK were enrolled. We measured the CS isomers chondroitin 4 sulfate
      and chondroitin 6 sulfate using an enzyme-linked immunosorbent assay
      preoperatively and postoperatively on days 1 and 4, week 1, and 1 and 3 months.
      RESULTS: The chondroitin 4 sulfate concentration remained unchanged from
      preoperative values. The chondroitin 6 sulfate concentration increased
      temporarily 1 day postoperatively and gradually decreased thereafter.
      CONCLUSIONS: CS in tear fluids participates in wound healing after LASIK.
      Clarifying its role in tear fluids will contribute to improved LASIK outcomes.

PMID- 16974129
TI  - Androgen status of the nonautoimmune dry eye subtypes.
AB  - PURPOSE: To evaluate androgen levels of patients diagnosed with nonautoimmune dry
      eye, either with meibomian gland dysfunction (MGD) or without MGD (non-MGD), and
      normal control subjects. This is a prospective, comparative, case-control study.
      METHODS: Sixty-four (32 men and 32 women) subjects were enrolled for each of the
      three diagnostic groups. All dry eye patients were symptom positive. Nonfasting
      testosterone (T), sex hormone-binding globulin, serum albumin,
      dehydroepiandrosterone (DHEA), and DHEA sulphate levels of all study participants
      were determined using either automated immunoenzymatic assay, or standard
      radioimmunoassay. Analysis of variance was used to compare androgen levels among
      the three diagnostic groups in a gender-based design, followed by post-hoc
      multiple comparisons with the Tukey honestly significant difference test.
      RESULTS: Mean T levels in men and women of the three diagnostic groups were not
      significantly different (p = 0.808, p = 0.156, respectively; ANOVA). Statistical
      analyses of the three diagnostic groups revealed a significant difference for men
      and women in bioavailable T levels (p = 0.002, p = 0.014, respectively; ANOVA),
      DHEA levels (p = 0.009, p = 0.004, respectively; ANOVA), and DHEA sulphate levels
      (p = 0.001, p = 0.001, respectively; ANOVA), whereas there was no statistically
      significant difference between non-MGD dry eye patients and controls for any of
      the measured androgen levels according to the post-hoc tests. CONCLUSION: This
      study demonstrates that the androgen pool of nonautoimmune dry eye patients with
      MGD is significantly depleted compared with that of non-MGD and control cases.

PMID- 16974130
TI  - The efficacy of postenucleation saline wash and the effect of different
      antimicrobial agents on microbial contamination of donor eyes.
AB  - OBJECTIVES: To evaluate the efficacy of postenucleation saline wash and the
      effect of different antimicrobial agents on the microbial contamination of donor
      eyes. METHODS: Two hundred donor eyes were given saline wash and treated with any
      one of the following 5 randomly selected antimicrobial solutions: 1% povidone
      iodine for 3 min, 0.3% gentamycin for 10 min, 0.3% ciprofloxacin for 10 min, a
      combination of neomycin 1,700 IU, gramicidin 0.025% and polymyxin B 5,000 IU
      (Neosporin(R)) for 10 min and a combination of 0.3% amikacin for 10 min, followed
      by 2.5% cefazolin for 10 min. Limbal swabs were sent for culture before and after
      saline wash and after treatment with antimicrobial agents. RESULTS: On culture of
      the pretreatment swabs, 77.5% were positive for growth with 75.5% bacterial and
      11.5% fungal. Coagulase-negative Staphylococcus (29.1%) was the most common
      bacterial contamination followed by Pseudomonas aeruginosa (18.5%), Acinetobacter
      sp. (18.5%) and Alcaligenes faecalis (13.2%). A 20-ml sterile saline wash
      resulted in a 20% decrease (p < 0.01) in the amount of contamination. The maximum
      antimicrobial effect with regard to bacterial decontamination was achieved with
      povidone-iodine (64% decrease in the amount of contamination, p < 0.01) followed
      by ciprofloxacin (47.6% decrease, p < 0.05), the combination of cefazolin and
      amikacin (42.5%, p < 0.05), Neosporin (38.5%, p < 0.05) and then gentamycin
      (21.7%, p = NS). CONCLUSIONS: A thorough saline wash and treatment with 1%
      povidone-iodine for 3 min is a more effective method for the decontamination of
      donor eyes as compared to most currently available and frequently used
      antibiotics.

PMID- 16974131
TI  - Pyridoxamine inhibits maillard reactions in diabetic rat lenses.
AB  - PURPOSE: Advanced glycation end products (AGEs) play an important role in protein
      modification during cataract formation. Along with sugars, alpha-dicarbonyl
      compounds, such as methylglyoxal (MGO), have been implicated in AGE formation.
      Here we report the effect of pyridoxamine (PM) on AGEs and AGE-precursor
      metabolizing enzymes in diabetic rat lenses and organ-cultured rat lenses.
      METHODS: Diabetes was induced in rats by injecting streptozotocin. Diabetic and
      nondiabetic control rats were treated with PM in drinking water for 20 weeks. Rat
      lenses were organ cultured with normal or high glucose. We measured lens
      glutathione (GSH), MGO, AGEs and activities of aldose reductase and glyoxalase I.
      RESULTS: Treatment of diabetic rats with PM inhibited both argpyrimidine and
      pentosidine formation when compared to untreated diabetic animals and nondiabetic
      control animals. Incubation of lenses with 30 mMD-glucose caused an elevation of
      these AGEs. Addition of 250 muM PM along with glucose resulted in inhibition of
      AGE formation in organ-cultured lenses. The glyoxalase I activity was
      significantly reduced in diabetic rats; PM treatment inhibited such a reduction.
      The activity of aldose reductase was elevated in diabetic lenses; PM treatment
      further enhanced its activity. CONCLUSION: Our results suggest that PM can
      inhibit AGE formation in the diabetic lens by enhancing the activity of aldose
      reductase and reacting with precursors of AGEs.

PMID- 16974132
TI  - Protective effect of aspirin against dexamethasone-induced cataract in cultured
      rat lens.
AB  - PURPOSE: To investigate the effect of aspirin on dexamethasone-induced cataract
      formation in cultured rat lenses. METHODS: One hundred and forty-eight lenses
      were divided into 3 groups and cultured in vitro: control (DMEM), cataract (DMEM
      + 10 microM dexamethasone), aspirin (DMEM + 10 muM dexamethasone + 2 mM aspirin).
      Following incubation, the transparency of the lenses was evaluated daily using a
      dissecting microscope. Twelve lenses from each group were homogenized and the
      activities of enzymes (catalase, superoxide dismutase and lactate dehydrogenase)
      from supernatants were measured after 1, 3, 5 and 7 days of incubation,
      respectively. The ultrastructure of lenses from the control and cataract groups
      was observed on the completion of 7-day incubation. RESULTS: Opacity was induced
      by dexamethasone in the nuclear region of the rat lenses. Lenses in the control
      group exhibited mist-like opacity and lenses in the cataract group showed dense
      nuclear opacity, whereas lenses in the aspirin-treated group only had a visible
      demarcation between nuclear and cortical regions at day 7. The activities of
      catalase, superoxide dismutase and lactate dehydrogenase in the cataract group
      decreased in a time-dependent manner. There was no significant loss of enzyme
      activities in either the control or the aspirin group throughout the incubation
      period. An orderly arrangement of fiber cells was noted, and the cell membrane,
      cell junction and organelles were normal in the control group. However, in the
      cataract group the arrangement of fiber cells was untidy and the lenses contained
      abnormal-appearing cells. The group exhibited swollen mitochondria, a large
      number of vacuoles and expanded extracellular lacunae. CONCLUSIONS: Dexamethasone
      induces nuclear cataract in the organ-cultured rat lens by chemically modifying
      proteins, including enzymes. The enzymes, including those that normally eliminate
      radial oxygen species, could be especially vulnerable. Aspirin significantly
      inhibits dexamethasone-induced cataract formation by inhibiting inactivation of
      those enzymes.

PMID- 16974133
TI  - Further investigation of the tolerance and mechanical adjustability of the
      *Acri.Tec AR-1 PC/IOL in rabbit eyes: an intraocular lens with reversibly
      adjustable optical power.
AB  - PURPOSE: To examine the tolerance and mechanical function of an adjustable
      intraocular lens (IOL) in rabbit eyes. METHODS: Implantation of the *Acri.Tec AR
      1 PC/IOL into 14 rabbit eyes. Manipulation of the lens 8 weeks after implantation
      in order to change the refractive power. Follow-up for up to 5 months.
      Histopathologic examination of the eyes. RESULTS: Implantation and mechanical
      adjustment of the PC/IOL were possible. Eyes healed normally. No difference
      between eyes containing the *Acri.Tec AR-1 PC/IOL and eyes containing the control
      PC/IOL could be detected with respect to signs of inflammatory reaction, corneal
      transparency, intraocular pressure and histopathologic appearance.
      Histopathologic examination of the eyes showed that the *Acri.Tec AR-1 PC/IOL did
      not cause any damage in rabbit eyes. CONCLUSION: The *Acri.Tec AR-1 PC/IOL is
      well tolerated in rabbit eyes for extended periods of time, suggesting that this
      PC/IOL should be well tolerated in the long run. Surgical adjustment of the
      adjusting element can be performed with little effort several weeks after
      implantation.

PMID- 16974134
TI  - Nasolacrimal endometriosis. A case report.
AB  - Endometriosis is the presence of endometrial tissue outside of the uterine
      cavity. In this paper, we present a patient with nasolacrimal system
      endometriosis which is a rare clinical condition.

PMID- 16974135
TI  - Differential role of rho-kinase in pathological and physiological cardiac
      hypertrophy in rats.
AB  - The present study was undertaken to investigate the effect of fasudil, a specific
      Rho-kinase inhibitor, in pathological cardiac hypertrophy induced by partial
      abdominal aortic constriction (PAAC) for 4 weeks in comparison with physiological
      cardiac hypertrophy caused by chronic swimming training (CST) for 8 weeks in
      rats. Fasudil (15 and 30 mg/kg day(-1) p.o.) treatment was started 3 days before
      PAAC and CST, and was continued for 4 weeks in PAAC and 8 weeks in the CST
      experimental model. Left ventricular (LV) function and LV hypertrophy were
      assessed by measuring LVDP, +dp/dt(max), -dp/dt(max), ratio of LV weight to body
      weight (LVW/BW), LV wall thickness (LVWT), LV collagen content, protein content
      and RNA concentration. Further, venous pressure (VP) and mean arterial blood
      pressure (MABP) were recorded. Moreover, DNA gel electrophoresis was employed to
      assess myocardial cell death. PAAC but not CST produced LV dysfunction by
      decreasing LVDP, +dp/dt(max), -dp/dt(max) and increasing LV collagen content.
      Further, PAAC and CST were noted to produce LV hypertrophy by increasing LVW/BW,
      LVWT, LV protein content and LV RNA concentration. Moreover, in contrast to CST,
      PAAC has significantly increased VP, MABP and LV necrotic cell death. Fasudil, a
      Rho-kinase inhibitor, markedly attenuated PAAC-induced LV dysfunction, LV
      hypertrophy, increase in VP, MABP and LV necrotic cell death. However, it did not
      modulate the CST-induced LV hypertrophy. These results have implicated Rho-kinase
      in PAAC-induced LV dysfunction and pathological cardiac hypertrophy. However, Rho
      kinase may not be involved in CST-induced physiological cardiac hypertrophy.

PMID- 16974136
TI  - Delusional misidentification syndrome: why such nosologic challenge remains
      intractable.
AB  - The delusional misidentification syndrome has lately been the object of lengthy
      psychopathological discussions. Controversies persist as to how best to define
      it, distinguish its subtypes and set their limits. Attempts to provide this
      syndrome with a better conceptual framework have usually relied on proposing new
      definitions and classifications. In this article, we suggest that some prevailing
      difficulties are basically related to two separate but intertwined issues: the
      self-reflexive property of the human mental functioning and the first-person
      linguistic expression of human experience. We argue that this discussion belongs
      to a broader context than the one it is usually referred to, as it deals with
      problems germane to conceptual psychopathological investigations in general. In
      that regard, DMS provides us with a very telling example, to the extent to which
      it has, at its core, to account for the puzzling phenomena of identity, which are
      particularly affected by cultural and linguistic variables.

PMID- 16974137
TI  - A qualitative examination of the experience of 'depression' in hospitalized
      medically ill patients.
AB  - BACKGROUND: Research into depression in the medically ill has progressed without
      sufficient attention being given to the validity, in this group, of the taxonomic
      categories. We aimed to describe, using qualitative interviews, the experience of
      'being depressed', separating experiences that are unique to depression from
      experiences that are common to being ill and in hospital. METHOD: Forty-nine
      patients hospitalized for medical illness underwent a 30-min interview in which
      they were asked to 'Describe how you have been unwell and, in particular, how
      that has made you feel.' From the transcripts, a 'folk' taxonomy was constructed
      using a phenomenological framework involving four steps: frame elicitation to
      identify the important themes, componential analysis to systematically cluster
      the attributes into domains, a comparison of the experiences of patients
      screening depressed and not-depressed, and a theoretical analysis comparing the
      resulting taxonomy with currently used theoretical constructs. RESULTS:
      Experiences common to all patients were being in hospital, being ill or in pain,
      adjusting to not being able to do things, and having time to think. In addition,
      all participants described being depressed, down or sad. Patients who were
      identified by screening as being depressed described unique experiences of
      depression, which included 'having to think about things' (a forceful intrusive
      thinking), 'not being able to sleep', 'having to rely on others', 'being a
      burden' to others (with associated shame and guilt), feelings of 'not getting
      better' and 'feeling like giving up'. Theoretical analysis suggested that this
      experience of depression fitted well with the concept of demoralization described
      by Jerome Frank. CONCLUSIONS: Demoralization, which involves feelings of being
      unable to cope, helplessness, hopelessness and diminished personal esteem,
      characterizes much of the depression seen in hospitalized medically ill patients.

PMID- 16974138
TI  - Community-associated MRSA: new guidelines for a new age.

PMID- 16974140
TI  - Competency in the clinical venue.

PMID- 16974141
TI  - Vestibular evoked myogenic potentials.
AB  - PURPOSE OF REVIEW: Vestibular evoked myogenic potential testing is the only
      clinically feasible way to measure function of the saccule. Interest in this test
      has exploded in recent years because of its potential utility in diagnosing third
      window disorders and in diagnosing and monitoring Meniere's disease. RECENT
      FINDINGS: Recent literature on vestibular evoked myogenic potential covers a wide
      range of topics. Review articles, method articles and many case reports and
      uncontrolled case series are seeking new applications for vestibular evoked
      myogenic potential in diagnosis and monitoring of neurotologic disease, and in
      shedding light on inner ear diseases by mapping anatomic sites of involvement.
      The most informative work is still in the areas of superior semicircular canal
      dehiscence and in Meniere's disease. Also, many aspects of vestibular evoked
      myogenic potential and its use have not yet been adequately studied or described.
      SUMMARY: Vestibular evoked myogenic potential is a new test of saccular and
      inferior vestibular nerve integrity. It holds great promise for diagnosing and
      monitoring Meniere's disease and some other neurotologic disorders. It is still
      an evolving field, however. The methods, equipment, and applications for
      vestibular evoked myogenic potential testing are not yet standardized. It is not
      yet time for this test to be widely applied, but that time is not far off.

PMID- 16974142
TI  - Controversies in building a management algorithm for vestibular schwannomas.
AB  - PURPOSE OF REVIEW: The present review examines the various mainstream treatment
      options, benefits and risks, and controversies involved in developing a
      management algorithm for treatment of vestibular schwannoma. RECENT FINDINGS:
      Advances in microsurgery and radiosurgery have made tremendous contributions to
      management of vestibular schwannoma; however, considerable controversy still
      exists. The auditory and facial nerve functional outcomes have improved with use
      of intraoperative monitoring for vestibular schwannoma removal and with lower
      radiosurgery doses; however, risks to the facial and auditory nerves still exist.
      Observing vestibular schwannomas for growth with serial magnetic resonance
      imaging is an increasingly popular option for small vestibular schwannomas that
      allows patients to enjoy hearing and facial function. SUMMARY: The risks and
      benefits of each treatment option must be weighed for each patient, and
      management decisions regarding vestibular schwannomas should be individualized
      for each patient depending on tumor anatomy, patient preferences, and symptoms.

PMID- 16974143
TI  - Implantable middle ear hearing devices: current state of technology and market
      challenges.
AB  - PURPOSE OF REVIEW: This review of implantable middle ear hearing devices is
      relevant to hearing professionals and otolaryngologists as an update of
      technological developments and the status of performance of current devices used
      in the United States. The 9th International Conference on Cochlear Implants and
      related Sciences was conducted 14-17 June in Vienna, Austria. Middle ear
      implantable devices were considered a 'hot topic', as two fully implantable
      devices are nearing European CE and FDA approval. RECENT FINDINGS: The main
      themes in this review focus on the fundamental technology applied to middle ear
      implantables, currently available devices, an overview of devices now off the US
      market and on challenges in improving performance and reliability. The necessary
      interplay with manufacturing devices which are more straightforward to surgically
      place and affordable enough to be accessed by the eligible population of people
      with hearing loss is discussed. SUMMARY: Indications for middle ear implantable
      hearing devices are expanding and the reliability of systems continues to
      improve. Solving problems related to affordability and access has made little
      progress in comparison, as evidenced by the poor performance of several
      'technologically successful' manufacturers in the US market.

PMID- 16974144
TI  - Who should be a stapes surgeon? An otologist or a generalist?
AB  - PURPOSE OF REVIEW: The overall experience with stapes surgery has declined, both
      within residency training programs, as well as in clinical practice. Does this
      change in the environment suggest that subspecialists rather than generalists
      manage patients with otosclerosis? RECENT FINDINGS: A decreasing availability of
      patients with clinical otosclerosis has encouraged trainees and practitioners to
      adopt strategies that will enable the maintenance of quality care to these
      patients. SUMMARY: Well trained generalists should be prepared to perform stapes
      surgery. Lack of experience or infrequent exposure to disease suggests that
      optimal care can be achieved by referring the patient to an experienced otologic
      surgeon.

PMID- 16974145
TI  - Prevention of cochlear implant electrode damage.
AB  - PURPOSE OF REVIEW: As the current trend in cochlear implantation is to prescribe
      cochlear implants for patients with residual hearing and to use electroacoustic
      stimulation, cochlear implant damage must be prevented. This article summarizes
      current research endeavors to prevent electrode insertion trauma and resulting
      hearing loss. RECENT FINDINGS: Alteration in surgical technique is necessary with
      each new electrode design. Nontraumatic surgical technique also requires
      minimizing acoustic trauma due to drilling the cochleostomy, mechanical damage
      from electrode insertion, potential infection, and fibrosis of the cochlea. The
      pattern of hearing loss following electrode insertion trauma is an immediate loss
      that results from direct trauma to the macroscopic elements of the cochlea and a
      delayed loss that may reflect the activation of inflammatory and cell death
      pathways. Therapies under investigation include glucocorticoids, inhibitors of
      cell death pathways, and hypothermia. SUMMARY: Electrode insertion trauma-induced
      hearing loss involves multiple mechanisms ranging from mechanical insertion
      trauma to activation of inflammatory and cell death pathways. The macroscopic
      mechanical damage to the cochlea may be prevented by improvement of electrode
      design and surgical technique. The molecular damage needs further studies to
      assess the efficacy of novel therapeutic strategies in preserving functional
      residual hearing.

PMID- 16974146
TI  - Delivery of drugs to the inner ear.
AB  - PURPOSE OF REVIEW: Inner ear delivery of medicines has been a rapidly expanding
      field in otolaryngology. This technique provides a minimally invasive way of
      managing a number of otolaryngologic diagnoses and promises to provide a
      therapeutic option for previously untreatable disorders. The purpose of this
      review is to examine the literature that has been published recently (since
      January of 2005) in this field and to explore how this new literature has
      impacted on current practices. RECENT FINDINGS: While there was a significant
      volume of work done in this area from 1995 to 2004, publication in this area has
      slowed considerably. The literature focuses on two areas: the treatment of
      Meniere's disease with gentamicin and the treatment of sudden sensorineural
      hearing loss with steroids. The most promising area in this field, which is the
      development of new medicines to treat a variety of disorders, has not progressed
      over the last 2 years. SUMMARY: Recent peer-reviewed publications have not had a
      significant impact on the transtympanic treatment of Meniere's disease or sudden
      sensorineural hearing loss. We will review the current practices in these two
      areas, discuss the newest developments and examine how we can progress the field
      over the next several years.

PMID- 16974147
TI  - Aquaporins and Meniere's disease.
AB  - PURPOSE OF REVIEW: Review of the role of aquaporins in inner ear homeostasis and
      potential role in the pathogenesis of Meniere's disease. RECENT FINDINGS: Recent
      findings include the immunolocalization of aquaporins in the inner ear of mouse,
      rat, and human to cell types that are likely to undergo high ionic perturbances
      (e.g. potassium flux) and to putative areas of endolymph resorption or cycling.
      SUMMARY: The expression of aquaporins and related proteins in the human cochlea
      and vestibular periphery resembles the distribution found in animal models,
      suggesting a critical role of aquaporins in inner ear water homeostasis and their
      potential role in the pathogenesis of Meniere's disease.

PMID- 16974148
TI  - Cochlear implant-mediated perception of music.
AB  - PURPOSE OF REVIEW: This paper examines and consolidates recent advances in
      cochlear implant sound processing from the perspective of music perception, which
      is increasingly viewed as one of the most difficult of all listening conditions.
      RECENT FINDINGS: Music is an essentially abstract, complex form of sound composed
      of multiple layers of sounds that vary in temporal presentation, frequency
      distribution, and harmonic content. As a result, music perception is perhaps the
      most challenging aspect of implant-mediated listening. Thus far, implant
      performance has shown poor performance overall during perception of musical
      pitches, melodies, and timbre while perception of rhythm is relatively good.
      Recent advances in implant sound processing strategies, particularly the use of
      current distribution along adjacent electrodes, have promising early results in
      terms of improving the number of pitch percepts available to cochlear implant
      listeners. SUMMARY: Music perception poses auditory challenges that can exceed
      those of language perception during cochlear implant-mediated listening. These
      challenges should be emphasized to patients prior to implantation. Although
      rhythm perception via cochlear implants is reasonably good using simple test
      paradigms, significant work remains to improve critically important aspects of
      music perception, including melody and timbre. New implant processing strategies
      are encouraging and should lead to improved music perception in the near future.

PMID- 16974149
TI  - Mouse models of otitis media.
AB  - PURPOSE OF REVIEW: Otitis media is one of the most prevalent inflammatory
      diseases in the pediatric population. The personal and societal costs for otitis
      media are significant. Problems arising from antibiotic use have led to
      considerable animal research efforts to better understand the mechanisms of acute
      otitis media and to develop new strategies for its prevention and treatment.
      RECENT FINDINGS: Various animal models induce acute otitis media from a variety
      of interventions, including direct injection of whole bacteria or their products
      into the middle ear. The mouse model has begun to emerge as a model for otitis
      media. The mouse affords many advantages for in-vivo research, including ease of
      genetic manipulation, availability of numerous inbred and transgenic strains, and
      an extensively studied immune system. Experimental reagents for cellular and
      molecular studies are widely available for the mouse. The mouse is an excellent
      model for investigating the genetics and molecular bases for otitis media due to
      the extensive understanding of the mouse genome. SUMMARY: With the increased
      availability of knockout and transgenic mice, and the large amount of data to
      indicate that human disease is accurately modeled in the mouse, the mouse model
      is increasingly becoming a model of choice.

PMID- 16974150
TI  - Current research in otosclerosis.
AB  - PURPOSE OF REVIEW: The aim of this article is to summarize and put into
      historical perspective current advances in research in otosclerosis, a disorder
      of the human temporal bone with a hereditary predisposition that is among the
      most common causes of acquired hearing loss. RECENT FINDINGS: Genetic studies
      have revealed that otosclerosis is heterogeneous, with evidence for defects in at
      least seven genes associated with six distinct chromosomal loci. Measurements of
      high levels of osteoprotegerin expression in the normal otic capsule and soft
      tissues of the cochlea provide the first molecular insight as to why the normal
      otic capsule remodels minimally, if at all. Osteoprotegerin knockout mice provide
      the best available animal model to date to study abnormal otic capsule remodeling
      that closely resembles otosclerosis. There is mounting evidence that the measles
      virus plays an important role in pathogenesis of otosclerosis although the
      mechanisms by which the virus results in otosclerosis remain unknown.
      Quantitative measures of angiogenesis can reliably distinguish between clinical
      and histological otosclerosis. Advances in the emerging field of osteoimmunology
      will likely impact and benefit from the research in otosclerosis. SUMMARY:
      Insights into molecular mechanisms that inhibit extensive remodeling in the
      normal otic capsule, and understanding of how these mechanisms are dysregulated
      in otosclerosis will allow future design of rational treatment strategies for
      otosclerosis.

PMID- 16974152
TI  - Current world literature.

PMID- 16974151
TI  - Tissue resistivities determine the current flow in the cochlea.
AB  - PURPOSE OF REVIEW: In individuals with severe to profound hearing loss, cochlear
      implants bypass normal inner ear function by applying electrical current directly
      into the cochlea, thereby stimulating cochlear nerve fibers. Stimulating discrete
      populations of spiral ganglion cells in cochlear implant users' ears is similar
      to the encoding of small acoustic frequency bands in a normal-hearing person's
      ear. Thus, spiral ganglion cells stimulated by an electrode convey the
      information contained by a small acoustic frequency band. Problems that refer to
      the current spread and subsequent nonselective stimulation of spiral ganglion
      cells in the cochlea are reviewed. RECENT FINDINGS: Cochlear anatomy and tissue
      properties determine the current path in the cochlea. Current spreads largely via
      scala tympani and across turns. While most of the current leaves the cochlea via
      the modiolus, the facial canal and the round window constitute additional natural
      escape paths for the current from the cochlea. Moreover, degenerative processes
      change tissue resistivities and thus may affect current spread in the cochlea.
      SUMMARY: Electrode design and coding strategies may result in more spatial
      stimulation of spiral ganglion cells, resulting in a better performance of the
      electrode-tissue interface.

PMID- 16974153
TI  - Comparison of corneal thickness of long-term contact lens wearers for different
      types of contact lenses.
AB  - PURPOSE: To compare the central corneal thickness (CCT) values of long-term
      wearers of different types of contact lenses with those of each other and a
      normal control group. METHODS: Twenty-three healthy eyes with no history of
      contact lens wear were used for the control group. Forty-eight eyes were
      evaluated in four different groups according to the type of contact lens worn;
      each group comprised 12 eyes. Group 1 (SofLens 38) and group 2 (Contact Day 30)
      had worn daily-wear frequent-replacement soft contact lenses with a 38% and 55%
      water content, respectively, and they had worn their lenses for an average of
      4.28 +/- 1.70 years and 3.71 +/- 1.11 years, respectively. Group 3 (Wohlk A90)
      and group 4 (Conflex-air) had worn daily-wear rigid gas-permeable (RGP) contact
      lenses with a Dk/t value of 68 and 22, respectively, and they had worn their
      lenses for an average of 3.00 +/- 0.63 years and 3.25 +/- 1.17 years,
      respectively. CCT values in micrometers were measured by optical coherence
      tomography. RESULTS: When comparing the CCT between the control group and the
      contact lens groups, the CCT was significantly thinner in the group wearing
      Conflex-air RGP contact lenses with a low Dk/t value (P = 0.010). In comparing
      the CCT among the four contact lens groups, the CCT was significantly thinner in
      the group wearing SofLens 38 contact lenses with a water content of 38% than in
      the group wearing Contact Day 30 contact lenses with a water content of 55% (P =
      0.004). There was also significant thinning in the group wearing Conflex-air RGP
      contact lenses versus the group wearing Contact Day 30 soft contact lenses (P =
      0.0005). CONCLUSIONS: CCT was significantly thinner in patients wearing long-term
      low-Dk/t RGP contact lenses compared to no contact lens wear and soft contact
      lenses with a water content of 55%. CCT was also decreased significantly in long
      term soft contact lens wear with a water content of 38% compared to 55%.

PMID- 16974154
TI  - Study of the factors associated with the presence of white dots in the corneas of
      regular soft contact lens users from an Asian country.
AB  - PURPOSE: : To investigate factors associated with the presence of microdot
      deposits or white dots (WDs) on confocal microscopy in regular soft contact lens
      (SCL) users. METHODS: : This cross-sectional observational study investigated
      changes in the cornea in regular SCL users by using an in vivo slit-scanning
      microscope (ConfoScan 3). Images were analyzed by noting the presence of highly
      reflective WDs. Factors associated with WDs were analyzed by using an unpaired t
      test with Welch correction. RESULTS: : There were 56 SCL wearers. Of these, a
      group of 10 had WDs (GWD) in various parts of the cornea. They had worn SCLs for
      7 to 20 years and had a mean total duration of SCL wear of 13.6 +/- 4.4 years.
      Their mean age was 35.8 +/- 10.4 years. They were compared with a group of SCL
      wearers with no evidence of WDs (GNWD). The mean age of GNWD was 29.1 +/- 7.2
      years, with a mean duration of SCL use of 8.17 +/- 5.1 years. The two groups were
      compared in terms of age, total duration of SCL wear (years), duration in hours
      per week, SCL water content (%), mean cell density in the endothelium and stroma,
      endothelial cell coefficient of cell size variation, and percentage of hexagonal
      cells. Only the duration of SCL wear was significantly associated with the
      presence of WDs (p=0.0042). WDs were most commonly found in the posterior stroma
      (n = 9). Two patients had WDs in the epithelium, with one of these having WDs in
      the endothelium. All patients except one with a hazy left eye scan had WDs
      bilaterally and symmetrically. CONCLUSIONS: : Confocal microscopy allows
      visualization of WDs in the corneas of Asian regular SCL users. Patients with WDs
      have a longer history of SCL wear. WDs may represent an early stage of corneal
      disease or degeneration associated with alterations in cell behavior.

PMID- 16974155
TI  - Clinical and in vivo confocal microscopy findings in patients receiving tamoxifen
      citrate.
AB  - PURPOSE: : To describe the deposition rate of tamoxifen in the cornea and observe
      its impact on the cornea with confocal microscopy. METHODS: : Forty-four eyes of
      22 women receiving tamoxifen at a dosage of 20 mg/day for at least 6 months for
      the adjuvant treatment of breast cancer and 30 eyes of 15 healthy age-matched
      women were examined for corneal drug deposition by slitlamp after pupil dilation.
      Ultrasound pachymetry, specular microscopy, in vivo confocal microscopy, and
      Schirmer tear test were also performed in all patients. RESULTS: : The mean
      duration of tamoxifen intake was 21.6 +/- 7.9 months (range, 13-44 months), and
      the mean cumulative dose was 12.9 +/- 4.7 g (range, 7.8-26.4 g). Drug depositions
      in the inferior paracentral cornea were identified in 32 (72%) eyes at pupil
      dilated slitlamp examination. There were no significant differences between eyes
      with keratopathy, those without keratopathy, and control eyes in regard to the
      mean Schirmer test scores, mean central corneal thickness, mean endothelial cell
      count, mean basal epithelium cell density, mean anterior and posterior stromal
      keratocyte density, and mean endothelial cell density (P > 0.05). No pathologic
      alteration of structure was observed with in vivo confocal microscopy at any
      corneal level in patients receiving tamoxifen. CONCLUSIONS: : Low-dose tamoxifen
      use was associated with corneal depositions in 72% of patients. Slitlamp
      examination performed with pupil dilation was helpful in detection of subtle
      tamoxifen-related deposits. Amelioration of in vivo confocal microscopy systems
      may be helpful in accurate imaging of the paracentral and peripheral cornea.

PMID- 16974156
TI  - Varieties of contact lens fittings after complicated hyperopic and myopic laser
      in situ keratomileusis.
AB  - PURPOSE: To determine whether contact lenses with a special back surface design
      can improve visual acuity after complicated laser in situ keratomileusis (LASIK).
      METHODS: Fifteen eyes (six after myopic LASIK and nine after hyperopic LASIK) of
      eight patients were fitted with contact lenses with a special back surface design
      for optical rehabilitation. Four different types of lenses (aspheric, tricurve,
      keratoconus, and reverse) were used selectively, depending on the abnormal
      eccentricity (positive and exceeding 0.5-0.7 in all preoperatively hyperopic
      eyes, negative in all preoperatively myopic eyes) determined by videokeratoscope
      and on individual conditions. The patients were followed up retrospectively for
      an average period of 12.3 months. Lens tolerance and corrected visual acuity were
      evaluated and compared with the results obtained with spectacles. RESULTS: Visual
      acuity improved in nine (60%) of 15 eyes (three eyes by more than three lines and
      six eyes by three lines or fewer), with an absence of halos and ghost images in
      four (26.7%) of 15 eyes accompanied by good contact lens tolerance and a
      satisfactory contact lens fit. There were no noticeable complications.
      CONCLUSIONS: Contact lens fitting after LASIK is a safe and reliable procedure
      for improving visual acuity and reducing complications, such as ghost images or
      irregular corneal surface. Depending on the eccentricity and therefore on the
      preoperative refraction, contact lenses with a special back surface design can
      minimize problems in contact lens fitting and can improve tolerance and visual
      results.

PMID- 16974157
TI  - Susceptibility testing of clinical isolates of pseudomonas aeruginosa to
      levofloxacin, moxifloxacin, and gatifloxacin as a guide to treating pseudomonas
      ocular infections.
AB  - PURPOSE: Pseudomonas aeruginosa ocular infections most frequently originate from
      an environmental source; successful treatment with various ocular antibiotics is
      well established. However, emergence of resistant clones to available antibiotics
      poses a real threat to successful treatment. The purpose of this study was to
      evaluate the antibiotic susceptibilities of 100 random clinical isolates of P.
      aeruginosa to levofloxacin, moxifloxacin, and gatifloxacin, potential agents for
      the treatment of ocular infections caused by this microorganism. METHODS: One
      hundred consecutive strains of P. aeruginosa were isolated from clinical
      specimens submitted to the clinical microbiology hospital laboratory. Duplicate
      isolates were not included. The minimum inhibitory concentrations (MICs) of these
      isolates were determined by using Etests, performed according to the
      manufacturer's instructions. American Type Culture Collection (ATCC) strains of
      Escherichia coli, P. aeruginosa, and Staphylococcus aureus served as reference
      controls. RESULTS: Although most isolates were susceptible to levofloxacin,
      moxifloxacin, and gatifloxacin and the MICs were not significantly different,
      significant numbers were resistant. The standardized controls rendered expected
      MICs. The susceptibility of the isolates varied with regard to source, and
      resistant strains showed increased resistance. CONCLUSIONS: Based on the data,
      the treatment of ocular infections caused by P. aeruginosa with levofloxacin,
      moxifloxacin, and gatifloxacin still has a high likelihood of success. However,
      six of the isolates collected were resistant to all three of the fluoroquinolones
      tested. Based on the data, clinicians must be aware that clinical resistance can
      occur even with the newer fluoroquinolones.

PMID- 16974158
TI  - Treatment of refractory vernal ulcers with large-diameter bandage contact lenses.
AB  - PURPOSE: To report two cases of refractory vernal ulcers in which the fitting of
      a large-diameter (22 mm) hydrogel (Contaflex T75) bandage contact lens (BCL)
      ameliorated the signs and symptoms of the condition. METHODS: Two patients with
      refractory vernal ulcers are described. Mechanisms of the effect of a large
      diameter lens across the ocular surface are discussed in this condition. RESULTS:
      The first patient is a 10-year-old boy who had been treated unsuccessfully for a
      left vernal corneal ulcer with topical prednisolone 0.5% and olopatadine. The
      vernal ulcer resolved 2 weeks after the fitting of a large-diameter BCL. The
      second patient is a 4-year-old boy who had been intolerant of all his previous
      topical medications partly because of his ocular discomfort in association with
      the right vernal ulcer. A large-diameter BCL was fitted in his right eye. The BCL
      was removed 2 weeks later with complete healing of the corneal vernal ulcer.
      Owing to his improved comfort, the patient was able to tolerate topical
      prednisolone 0.5% drops. CONCLUSIONS: Large-diameter BCLs may be a useful
      treatment option in the management of refractory vernal ulcers.

PMID- 16974159
TI  - Microkeratome preparation of lamellar corneal grafts.
AB  - PURPOSE: To evaluate the thickness and viability of microkeratome-prepared
      lamellar corneal grafts in cold storage. METHODS: Ten human corneas were
      sectioned with a mechanical microkeratome with a 350-microm depth head and stored
      in Optisol GS at 4 degrees C for 2 days to simulate an eye bank scenario. Central
      corneal thickness before and after mechanical microkeratome sectioning was
      measured by ultrasonic pachymetry. Endothelial cell viability was evaluated by
      trypan blue and alizarin red staining. RESULTS: Total corneal thickness
      immediately before microkeratome dissection was 562 +/- 51 microm. Anterior and
      posterior graft thicknesses were 296 +/- 111 microm and 270 +/- 74 microm,
      respectively, immediately after dissection, and 282 +/- 38 microm and 429 +/- 31
      microm, respectively, 2 days after storage. There was significant swelling in the
      posterior (P=0.005) but not the anterior grafts (P=0.386). The percentage of
      devitalized endothelial cells was 3.0% +/- 1.2%. CONCLUSIONS: Corneal lamellar
      grafts may possibly be precut in a centralized facility and stored cold before
      further distribution.

PMID- 16974160
TI  - Comparison of conventional and silicone hydrogel contact lenses for bullous
      keratoplasty.
AB  - PURPOSE: To compare the efficacy and safety of conventional lenses and silicone
      hydrogel lenses in the treatment of bullous keratopathy. The silicone hydrogel
      bandage contact lenses used were Focus NIGHT & DAY and PureVision. The
      conventional lens used was Sauflon 85%. METHODS: This was a prospective,
      comparative study of 22 patients with painful bullous keratopathy in one eye.
      Patients visited a specialty contact lens department and were fitted with all
      three different lens types in their affected eye for 1 month each, for a total
      duration of 3 months. The main outcome measures were comfort and pain relief,
      which patients scored on a scale that ranged from 1 to 5, with 1 being very poor
      and 5 being excellent. Doctors assessed the fit of the lens, its movement, and
      any deposit buildup. The statistical tests applied were the Kruskal-Wallis test
      and the Mann-Whitney test. RESULTS: Sixteen of the 22 patients (24 eyes)
      successfully completed 1 month's wear of all three bandage contact lenses. The
      median comfort score was 3.9 for PureVision, 3.8 for Focus NIGHT & DAY, and 2.8
      for Sauflon 85%; there was a statistical significance among the three groups
      (P=0.031). Silicone hydrogel lenses performed better than conventional lenses for
      comfort. The Mann-Whitney test showed that there was no statistically significant
      difference for comfort scores of Focus NIGHT & DAY versus PureVision (P<0.782) or
      of Focus NIGHT & DAY versus Sauflon 85% (P<0.073). However, there was a
      statistically significant difference for comfort scores of PureVision versus
      Sauflon 85% (P<0.0136). The median pain relief score was 3.8 for PureVision, 3.7
      for Focus NIGHT & DAY, and 3.2 for Sauflon 85%. There was no significant
      difference among the three lenses for pain relief score. All three lens types
      were similarly good with regard to contact lens fit, movement, and deposit
      buildup. CONCLUSIONS: The use of silicone hydrogel lenses are a safe and
      effective alternative to conventional contact lenses for the treatment of bullous
      keratopathy.

PMID- 16974162
TI  - The complex gastrointestinal patient and Jean Watson's Theory of Caring in
      nutrition support.
AB  - The care of the patient with gastrointestinal disease is complex and challenging.
      The reasons for the complexity are varied and different for each patient. Any of
      these variables can affect the nutritional health of the patient, an essential
      element of care that supports healing, recovery, and improved quality of life. A
      nutritional assessment, an evaluation of the patient's nutritional status, can be
      used to establish the patient's weight history, dietary habits, tolerances, and
      likes and dislikes. Intake and output values from this assessment provide
      information relating to the patient's ability to meet his or her nutritional
      requirements orally or whether alternate methods for nutrition support need be
      considered, such as a feeding tube or a central intravenous catheter. Parenteral
      nutrition is the intravenous nutrition supplementation required when the oral or
      enteral route for nutrition support is unavailable or impossible. In this
      article, a clinical case scenario for a 34-year-old man with a history of cancer
      and an extensive bowel resection will be presented to better explore the decision
      making process for determining appropriate nutrition support. In addition,
      various issues the health practitioner needs to consider when managing the
      nutritional health of the complex gastrointestinal patient will be explored,
      relative to Jean Watson's Theory of Caring.

PMID- 16974164
TI  - How the gastroenterology nurse can establish and meet career goals.
AB  - A career goal promotes professional growth for the gastroenterology nurse. Short
      term goals (achievable in less than one year) focus toward attaining a long-term
      goal (achievable in 5 to 10 years). The steps to achieving a career goal are self
      assessment, career goal development, action plan development, implementation of
      the action plan, evaluation, and the establishment of a new goal. A career goal
      must be specific, measurable, achievable, realistic, and have a specified time
      frame. A tailor-made action plan is a list of interventions to promote goal
      achievement within the specified time frame. A goal posted in a prominent area is
      less likely to be forgotten and can guide day-to-day activities. A career goal
      should be reviewed and revised at least annually. A professional resume documents
      these career achievements.

PMID- 16974165
TI  - Omega-3 fatty acids as adjunctive therapy in Crohns disease.
AB  - Crohns disease is an inflammatory bowel disease that can have a significant
      impact on the health of those afflicted. The etiology of the disease is unknown,
      but genetic, environmental, dietary, and immunological factors are thought to be
      involved. Multiple nutrients can become depleted during active disease due to
      inadequate intake or malabsorption. Preventing these deficiencies is paramount in
      the care of those suffering from Crohns disease. Often the traditional treatments
      (medications) have limited effectiveness and negative side effects that inhibit
      their use. Enteral nutrition has promising therapeutic benefits, but its use is
      often limited to the pediatric population due to poor patient acceptability.
      Omega-3 fatty acids have been investigated for their anti-inflammatory properties
      as an alternative to traditional care. This article reviews the etiology of
      Crohns disease, nutritional deficiencies, traditional treatments, and the use of
      omega-3 fatty acids in the prevention of Crohns recurrence. The results from
      clinical trials have been conflicting, but a new fish oil preparation that limits
      the side effects of traditional fish oil therapy shows promise as an adjunctive
      treatment for Crohns disease. Continued research is needed to validate these
      findings.

PMID- 16974167
TI  - A prospective study to assess the efficacy and patient tolerance of three bowel
      preparations for colonoscopy.
AB  - The adherence to the required clear liquid diet and a high-volume bowel cleansing
      solution prior to colonoscopy often leads to poor patient compliance and
      inadequate exams. This study evaluated the efficacy and patient tolerance of
      three bowel preparation regimens prior to colonoscopy. One hundred fourteen
      patients were randomized to one of three preparations. Group 1 was assigned a
      clear liquid diet/magnesium citrate and bisacodyl prep; group 2 was assigned to
      receive a diet kit/magnesium citrate and bisacodyl prep; and group 3 received a
      diet kit/polyethylene glycol electrolyte prep. The adequacy of bowel preparation
      was graded by the endoscopists performing the procedures. The preparations were
      rated by patients for tolerance, compliance, and side effects. The three methods
      of preparation did not prove to be significantly different in regards to efficacy
      of colon cleansing or patient tolerability. There was also no difference in
      compliance between the three regimens. There were no reported side effects in any
      of the study groups. This study suggests that a low-residue diet kit, given in
      conjunction with polyethylene glycol electrolyte or magnesium citrate and
      bisacodyl, produces adequate colon cleansing and patient tolerability.

PMID- 16974168
TI  - The patient experience of treatment for hepatitis C.
AB  - This study has used qualitative hermeneutics to explore the patient's experience
      of treatment for hepatitis C. Hepatitis C treatment may pose numerous physical
      and emotional challenges. There is a need to understand the experience from a
      holistic nursing perspective in order to facilitate the patient's well-being.
      Individuals undergoing combination treatment for hepatitis C participated in a
      hermeneutic dialogue, which provided the investigators with an emic perspective.
      Dialogue content, reflection, and preunderstanding were hermeneutically analyzed.
      Similar treatment experiences elicited four common emotions (sadness, anger,
      fear, and frustration). Analyzing the similar experiences led to two emerging
      themes: (1) "That is not who I am," connoted by rejecting the notion of being a
      "typical" patient, seeing treatment as not so bad, being "different" during
      treatment, and feeling abandoned because of treatment; and (2) "looking beyond
      the experience" was noted by looking for faith beyond traditional healthcare and
      looking for understanding. The hepatitis C treatment experience was seen as a
      process: having a start, a middle, and an end, without being all-consuming.
      Implications for holistic nursing care are presented.

PMID- 16974169
TI  - Minimum registered nurse staffing for patient care in the gastrointestinal
      endoscopy unit.

PMID- 16974170
TI  - The role of the nurse/associate in the placement of percutaneous endoscopic
      gastrostomy (PEG) tube.

PMID- 16974171
TI  - Use of interpreters.

PMID- 16974172
TI  - Rediscovery of purpose.

PMID- 16974174
TI  - The transformation of healthcare: a wicked problem.

PMID- 16974173
TI  - The critique: a necessary part of scientific inquiry.

PMID- 16974175
TI  - The effect of music on pain and acute confusion in older adults undergoing hip
      and knee surgery.
AB  - The purpose of this study was to examine the effects of music listening in older
      adults following hip or knee surgery. Acute confusion and pain after surgery can
      increase length of stay and reduce function. Study results demonstrate a
      reduction in acute confusion and pain and improved ambulation and higher
      satisfaction scores in older adults who listened to music.

PMID- 16974177
TI  - Ethnopharmacology: understanding how ethnicity can affect drug response is
      essential to providing culturally competent care.
AB  - Ethnopharmacologic research has revealed that ethnicity significantly affects
      drug response. Genetic or cultural factors, or both, may influence a given drug's
      pharmacokinetics (its absorption, metabolism, distribution, and elimination) and
      pharmacodynamics (its mechanism of action and effects at the target site), as
      well as patient adherence and education. In addition, the tremendous variation
      within each of the broader racial and ethnic categories defined by the U.S.
      Census Bureau (categories often used by researchers) must be considered. Nurses
      need to become knowledgeable about drugs that are likely to elicit varied
      responses in people with different ethnic backgrounds, as well as the potential
      for adverse effects. The existing ethnopharmacologic research focuses primarily
      on psychotropic and antihypertensive agents, as does this article. Cultural
      assessment of every patient is vital; thus Leininger's Sunrise Model and Giger
      and Davidhizar's Transcultural Assessment Models are briefly described as well.

PMID- 16974178
TI  - A theoretical discussion about the clinical value of phenomenology for nurses.
AB  - This article develops a theoretical discussion related to the value of a
      phenomenological framework in contributing to contemporary nursing knowledge.
      Nursing is based on the understanding of patients' personal experiences and their
      responses to their illness. Phenomenological methodology utilizes the patient's
      own language to reflect meanings embedded in their health experience.

PMID- 16974179
TI  - Holistic care facilitates seamless transitions for a community-dwelling elder: a
      case study.
AB  - Community-dwelling seniors with declining self-sufficiency are at risk for
      premature institutionalization. Early intervention while the senior has
      capabilities is the solution for guiding the elder to appropriate care along the
      continuum. This article demonstrates how a gerontological nurse as facilitator of
      healing helped an elder achieve the desired maximum quality of life.

PMID- 16974180
TI  - Complementary and alternative medicine: nurse practitioner education and
      practice.
AB  - The purpose of this article is to examine the current literature surrounding
      nurse practitioner knowledge and use of complementary and alternative medicine
      (CAM). Its use has increased over the last few decades, yet few healthcare
      practitioners ask their patients about CAM. Nurse practitioners need to be
      capable of addressing this use.

PMID- 16974181
TI  - Pediatric nursing in the context of the HIV/AIDS epidemic in resource-poor
      settings--balancing the "art and the science".
AB  - Pediatric wards in South Africa are largely occupied by children with AIDS
      related illnesses. This study uses qualitative inquiry involving focus groups
      with nurses into the needs of children, caregivers, and healthcare providers. The
      findings indicate changes to the nature of nursing practice, knowledge of
      nursing, and ethics of nursing care.

PMID- 16974182
TI  - Foot reflexology.

PMID- 16974183
TI  - Critical role of M3 muscarinic receptor in insulin secretion: implications for
      psychopharmacology.

PMID- 16974184
TI  - Randomized, double-blind 6-month comparison of olanzapine and quetiapine in
      patients with schizophrenia or schizoaffective disorder with prominent negative
      symptoms and poor functioning.
AB  - This study compared the effects of olanzapine (OLZ) with those of quetiapine
      (QUE) for improving negative symptoms in patients diagnosed with schizophrenia or
      schizoaffective disorder who had prominent negative symptoms and marked deficits
      in social or occupational functioning. In this 6-month, multicenter, double-blind
      clinical trial, patients were randomized to treatment with OLZ (n = 171, 10-20
      mg/d) or QUE (n = 175, 300-700 mg/d). Patients were treated at community mental
      health centers and assigned case managers who developed individualized
      psychosocial treatment plans. The primary efficacy measure was the reduction in
      negative symptoms using the Scale for the Assessment of Negative Symptoms.
      Secondary measures assessed changes in functioning, psychopathology, and
      treatment tolerability. Treatment with OLZ or QUE led to a significant reduction
      in negative symptoms, with no between-group difference (P = 0.09). Both treatment
      groups also showed significant improvement on most efficacy measures. Olanzapine
      treated patients showed significantly greater improvement on positive symptoms
      and on several measures of functioning including Global Assessment of Functioning
      Scale, Quality of Life Instrumental Role domain, and level of effort in
      psychosocial or occupational rehabilitation programs. Significantly more OLZ
      treated patients completed the study (52.6% OLZ, 37.7% QUE, P = 0.007). Treatment
      differences in safety were relatively small and not thought to be clinically
      relevant. Patients with schizophrenia who manifest prominent negative symptoms
      and marked functional deficits demonstrated significant improvement in negative
      symptoms after treatment with OLZ or QUE. Greater improvement in positive
      symptoms and a greater study completion rate may hold relevance to enhanced
      functional outcomes observed after OLZ therapy.

PMID- 16974185
TI  - Effects of an educational intervention on weight gain in patients treated with
      antipsychotics.
AB  - BACKGROUND: Increasing numbers of reports have raised concerns about significant
      increases in weight and adiposity over both short- and long-term treatment in
      patients treated with antipsychotics (APs). The management of overweight and
      obesity in patients treated with APs has included pharmacological interventions,
      dietary suggestions, and behavioral strategies. Nevertheless, current evidence
      does not support the use of pharmacological management of this specific type of
      obesity, and only a limited number of studies have been published regarding
      prevention and treatment of weight gain with other strategies. OBJECTIVE: The aim
      of this study was to evaluate the effectiveness of an educational intervention
      (EI) that combines low-calorie diet with increased physical activity to prevent
      and treat weight gain in patients treated with APs. METHOD: Data were from 53
      subjects whose body mass index (BMI) had increased by more than 7% after starting
      an AP therapy and who consented to participate in a 12-week educational
      intervention study aimed at preventing further weight gain and, when possible, at
      inducing a weight loss. Weight and BMI were measured at baseline (at each of the
      monthly follow-up visits) and at study completion 12 weeks from entry in the
      study. RESULTS: Twenty-six patients completed the 12-week program. Completers
      showed a significant mean body weight decrease of 3.15 kg, with a mean BMI
      reduction of 1.2 (kg/m) at the end of the 3-month period. CONCLUSIONS:
      Educational intervention can be an important tool for the management of weight
      increase in patients treated with APs. A larger prospective and controlled study
      is now needed to confirm our findings.

PMID- 16974186
TI  - Efficacy of topiramate, valproate, and their combination on aggression/agitation
      behavior in patients with psychosis.
AB  - Topiramate is an antiepileptic drug, recently also used in the treatment of
      psychiatric diseases. Inasmuch as topiramate and valproate, which are currently
      used for aggressive behavior, share several pharmacological mechanisms (positive
      modulatory effect on the GABA activity and negative modulatory effect on
      glutamatergic neurotransmission), the objective of the present study was to
      compare the pharmacological effects of topiramate with those of valproate and
      their combination in patients with psychiatric disorders showing marked
      aggression and agitation. A retrospective, case-controlled, mirror-image study
      was carried out in a sample of 45 inpatients affected by schizophrenia,
      schizoaffective and bipolar disorder, and hospitalized in a maximum-security
      Canadian psychiatry hospital. Overt Aggression Scale, Agitation-Calmness
      Evaluation Scale, number and intensity of psychotic episodes, number of episodes
      of withdrawal from group activities per week, and number of therapeutic isolation
      per week and of strict surveillance intervention per week were evaluated before
      and after the treatments. Results indicate that patients treated with topiramate
      show a decrease in the average score of the Overt Aggression Scale, a decrease of
      episodes of agitation and of strict surveillance interventions. This effect was
      similar to the group treated with valproate or with the combination of valproate
      topiramate. However, valproate therapy, but not topiramate therapy, decreased the
      intensity of agitation episodes measured by the Agitation-Calmness Evaluation
      Scale; valproate and the combination topiramate-valproate decreased the number of
      psychotic disorganization episodes as well. These results suggest that topiramate
      could be a valid medicine in the control of aggression in psychosis. Double
      blind, randomized, placebo-controlled studies need to further assess this
      pharmacological indication.

PMID- 16974188
TI  - Modification of behavior with 50% nitrous oxide/oxygen conscious sedation over
      repeated visits for dental treatment a 3-year prospective study.
AB  - In various medical domains, inhalation of nitrous oxide (N2O) in oxygen (O2) is
      indicated to alleviate pain and anxiety during routine treatment. Repeat
      treatment may often be indicated. Little data are available, however, to evaluate
      the long-term efficacy and side effects of reiterated N2O/O2 sedation. The aim of
      this study was to compare behavior during dental treatment under a premix of 50%
      N2O/O2 between first experience and repeat experiences of sedation in a cohort of
      uncooperative patients. Five hundred forty-three patients (age range, 1-94 years;
      mean, 17 +/- 16 years) experiencing conscious sedation for dental treatment for
      the first time were recruited at a special care unit during 3 years. A modified
      Venham scale was used to evaluate patient behavior at 5 steps during each
      session. Completion of planned treatment and occurrence of adverse side effects
      of sedation were additional criteria. Patients experienced sedation for the first
      time for 378 sessions, and the session was a repeat experience in 843 cases
      (number of visits: range, 1-6). Patient cooperation significantly improved during
      visits at first contact with the dentist and when applying the mask (P < 0.0001,
      between sessions 1 and 2). Between the first and the third sessions, the
      percentage of very uncooperative patients decreased from 23% to 3.7% at first
      contact with the dentist and from 22.3% to 8.5% on application of the mask.
      Experience of reiterated dental treatment under sedation with 50% N2O/O2 premix
      helps uncooperative patients to cope with dental treatment in the long term.

PMID- 16974189
TI  - A double-blind comparison between bupropion XL and venlafaxine XR: sexual
      functioning, antidepressant efficacy, and tolerability.
AB  - In this double-blind, multicenter study, bupropion XL, a norepinephrine-dopamine
      reuptake inhibitor, and venlafaxine XR, a serotonin-norepinephrine reuptake
      inhibitor, were compared with regard to sexual functioning, efficacy, and
      tolerability. A total of 348 sexually active adult outpatients with depression
      were randomized to receive bupropion XL (titrated to a target dose of 300-450
      mg/d) or venlafaxine XR (titrated to a target dose of 150-225 mg/d) for 12 weeks.
      Total scores on the primary dependent variable, the Changes in Sexual Functioning
      Questionnaire (self-report), increased for subjects receiving bupropion XL and
      decreased for those treated with venlafaxine XR; the mean change scores differed
      significantly between groups from week 2 onward. Among subjects with normal
      pretreatment sexual functioning, Changes in Sexual Functioning Questionnaire
      total scores remained essentially unchanged for the bupropion XL group but were
      decreased significantly for the venlafaxine XR group; mean change scores also
      differed between groups from week 2 onward. Although the therapies resulted in
      similar change on the 17-item Hamilton Depression Rating Scale, remission rates
      were significantly higher among those treated with bupropion XL (46%) versus
      venlafaxine XR (33%) (odds ratio, 1.93; 95% confidence interval, 1.07-3.46).
      Aside from adverse effects of venlafaxine XR on sexual function, both treatments
      were reasonably well tolerated. In conclusion, in this patient population (ie,
      relatively young, sexually active outpatients), bupropion XL was at least as
      effective as venlafaxine XR and had a significantly more favorable sexual side
      effect profile.

PMID- 16974190
TI  - Sex selection bias in schizophrenia antipsychotic trials.
AB  - The sex prevalence of schizophrenia is approximately equal, and yet clinical
      trials of new therapeutic drugs have been conducted, for the most part, with male
      participants. The authors reviewed the percentage of women in schizophrenia
      clinical trials of the new "atypical" antipsychotic medications. MEDLINE and
      Cochrane databases were searched for English-language randomized controlled
      trials involving risperidone, olanzapine, quetiapine, ziprasidone, and
      aripiprazole. Studies with a sample size of more than 50 and a subject diagnosis
      of schizophrenia, schizophrenia spectrum disorder, or broad psychosis were
      included for review. For each study, the following items were abstracted: source
      of support, pharmacotherapy, site location, treatment setting, patient phase,
      psychotic episode number, duration, number of men and women in the total sample,
      mean age of the sample, and the presence of women-specific inclusion/exclusion
      criteria. Sixty-seven published studies met criteria. The median percentage of
      women in the total sample was 33.3%, the minimum was 6.7%, and the maximum was
      71.2%. A stepwise linear regression analysis showed that age (younger samples),
      center location (Unites States and Canada), treatment patient setting
      (inpatient), and ziprasidone trials were all associated with relatively lower
      percentages of women. Sex differences in antipsychotic pharmacokinetics and
      pharmacodynamics that may result in differential effectiveness and susceptibility
      to adverse effects cannot be ascertained when the percentage of women in clinical
      trials is as low as it is. The increasing shift toward outpatient rather than
      inpatient drug trials may help to increase the proportion of women.

PMID- 16974191
TI  - Improvement of sustained attention and visual and movement skills, but not
      clinical symptoms, after dehydroepiandrosterone augmentation in schizophrenia: a
      randomized, double-blind, placebo-controlled, crossover trial.
AB  - BACKGROUND: Dehydroepiandrosterone (DHEA) augmentation has been reported, in a
      preliminary fashion, to be useful in the management of schizophrenia symptoms and
      side effects. In this study, the intention was to investigate the efficacy and
      safety of DHEA administration to ongoing antipsychotic medication in a
      multicenter, 12-week, double-blind, randomized, placebo-controlled, crossover
      trial. METHODS: Fifty-five of 62 inpatients and outpatients with Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of
      schizophrenia completed the trial. Patients were randomly allocated to 2
      treatment groups receiving either DHEA (200 mg/d) or placebo for 6 weeks with the
      crossover between DHEA and placebo occurring after 6 weeks. Patients continued to
      receive their regular antipsychotic medication for the duration of the study.
      RESULTS: Compared with placebo, DHEA administration did not produce significant
      improvement in clinical symptoms, side effects, and quality-of-life scores.
      However, 6 weeks of DHEA administration (but not placebo) was associated with a
      significant improvement in Positive and Negative Symptom Scale ratings compared
      with baseline. Furthermore, 6 weeks of DHEA treatment was associated with
      significant improvement in cognitive functions of visual sustained attention and
      visual and movement skills compared with placebo conditions. The DHEA
      augmentation was associated with elevations of serum concentrations of both DHEA
      and its sulfate ester. The DHEA treatment was well tolerated without any serious
      adverse effects. CONCLUSION: This short-term study does not support DHEA's value
      as an effective adjunct in the treatment of symptoms, side effects, and quality
      of-life impairment in schizophrenia, while suggesting that DHEA improves
      sustained attention and visual and movement skills. A long-term, large-scale
      study with a broader dose range is warranted to further investigate DHEA's role
      in the management of schizophrenia.

PMID- 16974192
TI  - Association between antipsychotic-induced elevation of liver enzymes and weight
      gain: a prospective study.
AB  - We conducted a prospective, open study in schizophrenia patients treated with
      second-generation antipsychotics in order to investigate the risk for elevation
      of liver enzymes and its correlation to antipsychotic-induced weight gain. Body
      mass index, serum transaminases, plasma serum levels of the antipsychotic used,
      and blood cell counts were measured weekly during the first 6 weeks of treatment
      and monthly thereafter. A considerable proportion of subjects showed an increase
      beyond normal levels of at least one of the measured transaminases. In all but
      one case, the elevation of liver enzymes was transient. We found a statistically
      significant correlation between weight gain and liver enzyme elevation. The group
      of patients that had gained at least 7% of the baseline body weight showed
      significantly higher increases of transaminases as compared with those who had
      gained less than 7% weight. We conclude that antipsychotic-induced elevation of
      liver enzymes is mostly transient and could be associated with weight gain.

PMID- 16974193
TI  - The early effect of olanzapine and risperidone on insulin secretion in atypical
      naive schizophrenic patients.
AB  - Recently, increasing attention has been drawn to the potential diabetogenic
      effect of atypical antipsychotics. The goal of this prospective study is to
      evaluate the early effect of olanzapine and risperidone treatment on pancreatic
      beta-cell function in atypical-naive schizophrenic patients. Twenty-six subjects
      were assigned randomly to therapy with olanzapine or risperidone for 14 days. The
      metabolic parameters were quantitatively assessed by using the intravenous
      glucose tolerance test. The levels of fasting glucose, fasting insulin, lipid
      profiles, and leptin were also assessed. There were no significant within-group
      changes in weight or body mass index for both groups after 2 weeks of treatment.
      The levels of fasting glucose, fasting insulin, cholesterol, or leptin did not
      change in both groups. The triglyceride level significantly increased in
      olanzapine group. Glucose disappearance rate and insulin sensitivity did not
      change in both groups. Insulin secretion significantly decreased in olanzapine
      group. After 2 weeks of olanzapine treatment, schizophrenic patients decreased
      insulin secretory response to a hyperglycemic challenge. The results of this
      study support the hypothesis that olanzapine might directly impair pancreatic
      beta-cell function.

PMID- 16974194
TI  - Quetiapine augmentation in lactation: a series of case reports.
AB  - Treating psychiatric disorders with pharmacotherapy in the breast-feeding period
      presents a dilemma as such treatment carries the risk of infant exposure to
      medication through breast milk. However, failure to institute pharmacotherapy in
      postnatal women in need of such treatment exposes both mother and baby to
      detrimental effects of the illness. Because women presenting with psychiatric
      disorders during the postpartum period often have complex sets of symptoms,
      monotherapy may not be sufficient for symptom resolution. In this case series of
      6, we examined levels of psychotropic medications secreted in breast milk and
      performed developmental assessments of the exposed babies with the Bayley Scales
      of Infant Development, Second Edition. In 3 of the 6 cases, no medication was
      detected in the breast milk; in all but 1 case, estimated levels of infant
      medication exposure were calculated to be less than 0.01 mg/kg per day for each
      medication. Four of the 6 babies scored as being within normal limits on the
      Bayley Scales of Infant Development, Second Edition, whereas 2 showed mild
      developmental delays. In comparison to the 4 cases of typical development, the 2
      showing mild delays did not have higher estimated levels of psychotropic
      medication exposure through breast milk. Based on these results, in our limited
      sample, there appears to be low levels of infant exposure to the medications
      through breast milk; no association was seen between developmental outcomes and
      exposure through breast milk of multiple pharmacological agents. These results
      should be interpreted with caution, and vigilance should be exercised when
      advising women on combinations of medications for severe mental illness who
      choose to nurse.

PMID- 16974195
TI  - Manic/hypomanic switch during acute antidepressant treatment for unipolar
      depression.
AB  - A significant proportion of patients with unipolar depression clinically develop
      manic or hypomanic switch during acute antidepressant treatment. Elucidation of
      its prevalence and predicting factors is of clinical relevance during acute
      antidepressant treatment of such patients. We retrospectively studied patients
      with unipolar depression who were admitted to our department during the 6-year
      period from 1997 to 2002 and who had fewer than 3 previous episodes before
      admission. The clinical background of the consecutive patients with
      manic/hypomanic switch (n = 37) who met Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition criteria was compared with that of patients
      without manic/hypomanic switch (n = 245). The prevalence rate of manic/hypomanic
      switch was 13.1%. The switch group was composed of 23 men and 14 women, whose
      average age was 48.8 +/- 12.3 years (range, 26-78 years). Manic/hypomanic switch
      was most frequently observed between 2 and 3 weeks after the antidepressant was
      increased to the ongoing dose. Antidepressants were decreased in 13 patients and
      discontinued in 23. Manic/hypomanic episodes lasted from 1 to 8 weeks. The
      patients in the switch group included a greater proportion of male subjects and
      had a higher frequency of family history of bipolar disorders than those in the
      nonswitch group. The mean doses of antidepressants were not significantly
      different between these groups. The higher frequency of manic/hypomanic switch
      occurring around the period when antidepressants begin to show clinical effects
      and the higher frequency of family history of bipolar disorders might suggest a
      biological susceptibility to antidepressants in patients of the switch group.

PMID- 16974196
TI  - Naturalistic long-term use of methylphenidate in bipolar disorder.
AB  - Antidepressant use seems to be problematic in bipolar disorder. The dopaminergic
      agent, bupropion, seems to be equally effective to serotoninergic agents but with
      greater safety. Methylphenidate is a stimulant medication that is sometimes used
      as an antidepressant in bipolar adults and is frequently used in children with
      comorbid bipolar and attention-deficit disorder. There are no data available for
      the safety of long-term methylphenidate in adults. A retrospective chart review
      of bipolar patients who received methylphenidate while attending a bipolar clinic
      was conducted. Data regarding side effects and symptoms were collected. Sixteen
      charts were reviewed. The mean duration of methylphenidate treatment was 14
      months (+/-SD, +/-17.5 months; range, 1-60 months). Five had comorbid attention
      deficit disorder, the remainder received the methylphenidate for depression. The
      mean dose was 16.3 mg/d (+/-SD, +/-8.7 mg/d; range, 5-40 mg/d). Several mild to
      moderate side effects were reported. Two patients (12.5%) discontinued
      methylphenidate because of adverse side effects. When available (44% of the
      sample), general assessment of function increased from (+/-SD) 48.3 +/- 9.9 to
      69.3 +/- 10.6 (P = 0.006). Methylphenidate seems to be safe in the naturalistic
      setting. Controlled studies are needed to confirm its efficacy and safety in
      bipolar depression.

PMID- 16974197
TI  - Abrupt discontinuation of alprazolam and cognitive style in patients with panic
      disorder: early effects on mood, performance, and vital signs.
AB  - The objective of this study was to ascertain the relationship of alprazolam
      plasma levels and an anxiety-prone cognitive style to the characteristics and
      severity of early withdrawal after abrupt discontinuation of alprazolam in 26
      patients with panic disorder. After 8 and 9 weeks of fixed-dose treatment,
      patients were hospitalized for 24 hours. On 1 admission, ordered at random,
      treatment was maintained; on the other, placebo was substituted double blind. The
      Anxious Thoughts and Tendencies questionnaire was administered before treatment.
      Alprazolam plasma levels were measured 7 times on the day after each admission.
      Before each blood sampling, the Profile of Mood States and performance tasks were
      administered, and vital signs were recorded. On the day after abrupt
      discontinuation of alprazolam, Profile of Mood States anxiety, depression,
      fatigue, and confusion increased; vigor and elation decreased; speed on the digit
      symbol substitution task improved; and systolic blood pressure increased
      substantially over time. High Anxious Thoughts and Tendencies scores were related
      specifically to more anxiety. Our findings (1) confirm that dysphoric mood,
      fatigue, low energy, confusion, and elevated systolic blood pressure are part of
      the early syndrome of withdrawal from alprazolam in patients with panic disorder,
      notably as the drop in plasma levels approaches 50%; (2) indicate a psychomotor
      deficit persisting beyond dose stabilization; (3) suggest that an anxiety-prone
      cognitive style measurable before undertaking treatment may be a risk factor for
      more severe anxiety upon discontinuation; and (4) provide a rationale for
      applying cognitive behavior therapy during benzodiazepine taper.

PMID- 16974200
TI  - Use of long-acting risperidone in the treatment of bipolar patients.

PMID- 16974199
TI  - Gamma-hydroxybutyrate and ethanol effects and interactions in humans.
AB  - BACKGROUND: Gamma-hydroxybutyrate (GHB) is a common drug of abuse that can
      produce serious toxicity, particularly when used with other sedatives. We
      examined the individual and combined effects of GHB and ethanol in human
      volunteers. METHODS: Sixteen healthy adults (7 men) were given 50 mg/kg GHB
      (Xyrem), 0.6 g/kg ethanol in 2 doses, alone and combined in a double-blind,
      placebo-controlled, crossover study. Plasma concentrations, heart rate (HR),
      blood pressure (BP), and oxygen saturation (O2sat) were serially monitored for 24
      hours. RESULTS: Adverse events included 2 instances of hypotension and 6 episodes
      of vomiting with GHB-plus-ethanol ingestion. Oxygen saturation was decreased by
      GHB and ethanol individually, and maximally decreased by the drugs combined (max 
      2.1% +/- 0.3%, P < 0.0001 vs placebo). Compared with baseline, systolic and
      diastolic BP were significantly decreased, and HR was increased by ethanol but
      not affected by GHB alone (maximum systolic BP change -15.7 +/- 3.0 mm Hg, P =
      0.0006; maximum HR change 13.5 +/- 2.3 beats per minute, P = 0.006). Ethanol
      coingestion resulted in 16% higher GHB maximal plasma concentration and 29%
      longer elimination half-life, indicating possible enhanced bioavailability or
      reduced clearance of GHB caused by ethanol, however, these effects were not
      statistically significant. CONCLUSIONS: Modest doses of GHB do not affect
      hemodynamic function, but O2sat was decreased. Gamma-hydroxybutyrate-plus-ethanol
      resulted in more adverse effects, including gastrointestinal disturbances,
      hypotension, and decreased O2sat, but only minimal pharmacokinetic interactions
      were observed.

PMID- 16974201
TI  - Perospirone is a new generation antipsychotic: evidence from a positron emission
      tomography study of serotonin 2 and D2 receptor occupancy in the living human
      brain.

PMID- 16974202
TI  - An exploratory open trial on safety and efficacy of the anticonvulsant retigabine
      in acute manic patients.

PMID- 16974203
TI  - Atypical neuroleptic malignant syndrome associated with aripiprazole.

PMID- 16974204
TI  - Excretion of escitalopram in breast milk.

PMID- 16974205
TI  - Panic disorder, treatment with selective serotonin reuptake inhibitors, and
      cholesterol levels.

PMID- 16974206
TI  - Anxiolytic effect of rescue remedy for psychiatric patients: a double-blind,
      placebo-controlled, randomized trial.

PMID- 16974207
TI  - Sustained effects of phenelzine and tranylcypromine on orthostatic challenge in
      antidepressant-refractory depression.

PMID- 16974208
TI  - Lack of effect of chromium supplementation on mental state and body weight in
      people with schizophrenia.

PMID- 16974209
TI  - High-dose quetiapine and photopsia.

PMID- 16974210
TI  - Survival and restoration of pulmonary perfusion in a long-term follow-up of
      patients after acute pulmonary embolism.
AB  - We followed prospectively 834 consecutive patients (70% inpatients), evaluated
      for suspected pulmonary embolism, for a median time of 2.1 years (range, 0-4.8
      yr), and compared the survival rates in patients with proven pulmonary embolism
      (n=320) with those without (n=514). In multivariate analysis, we modeled the
      probability of surviving in patients with pulmonary embolism as a function of the
      extent of pulmonary vascular obstruction at baseline. Among patients with
      pulmonary embolism, a scintigraphic follow-up was pursued to assess the
      restoration of pulmonary perfusion over a 1-year period. We found that massive
      pulmonary embolism (vascular obstruction>or=50%) is a risk factor for mortality
      within the first few days after onset but, subsequently, has no significant
      effect on survival. The adjusted risk of death in patients with massive pulmonary
      embolism was 8-fold higher than in patients without embolism within the first day
      after the incident event. By contrast, the adjusted risk of death for patients
      with minor or moderate pulmonary embolism (vascular obstruction<50%) was no
      higher than in patients without embolism at any time after onset. Most of the
      patients who survived a year after pulmonary embolism showed a nearly complete
      restoration of pulmonary perfusion with a considerable improvement in arterial
      oxygenation. Four (1%) of the 320 patients with pulmonary embolism at
      presentation developed chronic thromboembolic pulmonary hypertension. These
      patients featured persistent large perfusion defects in sequential lung scans.
      Pulmonary embolism with vascular obstruction>or=50% is a strong, independent
      predictor of reduced short-term survival. This underscores the need for a prompt
      diagnosis of the disease. Monitoring the resolution of pulmonary embolism by lung
      scanning may prove useful in identifying patients with persistent perfusion
      abnormalities who may be at risk of chronic thromboembolic pulmonary
      hypertension.

PMID- 16974211
TI  - Unusual presentations of coccidioidomycosis: a case series and review of the
      literature.
AB  - Coccidioidomycosis is an emerging fungal infection of the southwestern United
      States. Although Coccidioides species infections are usually asymptomatic or
      result in a mild, flu-like illness, disseminated disease may occur in 1% of
      cases. While extrapulmonary disease usually involves the skin, central nervous
      system, bones, or joints, coccidioidomycosis is a great imitator, with the
      ability to infect any tissue or organ. Cases may be diagnosed outside of endemic
      areas, hence providers worldwide should be aware of the broad range of
      manifestations of coccidioidomycosis. We present a case series of unusual
      presentations of coccidioidomycosis including serous cavity infections with cases
      of pericarditis, empyema, and peritonitis, as well as unusual abscesses involving
      the retropharyngeal space and gluteal musculature. We provide a complete review
      of the literature and summarize the clinical presentations, diagnoses, and
      treatments of these rare forms of disseminated coccidioidomycosis.

PMID- 16974212
TI  - Respiratory viral infections in adults with hematologic malignancies and human
      stem cell transplantation recipients: a retrospective study at a major cancer
      center.
AB  - Community respiratory viruses (CRVs) have been recognized as a potential cause of
      pneumonia and death among hematopoietic stem cell transplantation (HSCT)
      recipients and patients with hematologic malignancies. We reviewed the
      Microbiology Laboratory records dated from July 1, 2000, to June 30, 2002, to
      identify patients who had respiratory specimens positive for influenza,
      parainfluenza, respiratory syncytial virus, or picornavirus. We identified 343
      infections among patients with underlying hematologic malignancies and HSCT. We
      collected data on type of disease, age, sex, type of infection, neutrophil and
      lymphocyte counts, therapy, and outcome. Influenza, parainfluenza, and
      respiratory syncytial virus accounted for most cases and were approximately equal
      in frequency. Most infections occurred predominantly among recipients of
      allogeneic transplants. Infection progressed to pneumonia in 119 patients (35%)
      and occurred with similar frequency for the 3 viruses. Patients at greatest risk
      for developing pneumonia included those with leukemia, those aged more than 65
      years, and those with severe neutropenia or lymphopenia. Lack of respiratory
      syncytial virus-directed antiviral therapy (p=0.025) and age (p=0.042) were
      associated with development of respiratory syncytial virus pneumonia, and an
      absolute lymphocyte count<or=200 cells/mL (p=0.049) was associated with
      development of influenza pneumonia. The overall mortality rate for CRV pneumonia
      was 15%. The only independent predictor of fatal outcome was an absolute
      lymphocyte count<or=200 cells/mL (p=0.03) in patients with influenza
      pneumonia.HSCT recipients and patients with hematologic malignancies who develop
      upper respiratory infection due to CRVs should be considered for antiviral
      therapy of proven efficacy to reduce the risk of pneumonia and death.

PMID- 16974213
TI  - Gender modifies the influence of age on outcome after successfully resuscitated
      cardiac arrest: a retrospective cohort study.
AB  - Age is an important risk factor for mortality and unfavorable outcome after
      successfully resuscitated cardiac arrest. Other risk factors may interact with
      this relationship. We conducted the current study to quantify the influence of
      age on mortality and unfavorable neurologic outcome of patients surviving out-of
      hospital cardiac arrest, and to determine the role of other confounding
      variables. This study was based on a cardiac arrest registry comprising all
      patients with witnessed out-of-hospital cardiac arrest of cardiac origin after
      successful resuscitation admitted to a department of emergency medicine between
      September 1991 and December 2004. We assessed the association between age and
      mortality and the degree of neurologic impairment, adjusting for multiple risk
      factors. We tested for interaction between age and all other risk factors with
      outcome. With each year of age the adjusted odds ratio for in-hospital death
      increased by 1.05 (95% confidence interval [CI], 1.04-1.07), and the adjusted
      odds ratio for an unfavorable neurologic outcome increased by 1.04 (95% CI, 1.03
      1.06). Interaction between age and sex was present, and the analysis was
      stratified to sex. For men we found a steep risk increase for death and
      unfavorable outcome after being resuscitated from cardiac arrest, with the
      highest risk in the oldest age quartile. For women we observed only a slight risk
      increase for death and almost no risk increase for unfavorable outcome. Age is a
      strong independent risk factor for mortality and neurologic impairment after
      successfully resuscitated cardiac arrest. The risk increase with advancing age is
      much greater in men than in women. Therefore, in women, the influence of age on
      prognosis after cardiac arrest may not be very important, while in men it still
      plays an important role. This should be considered especially when treating
      successfully resuscitated women and discussing the prognosis with the medical
      team or the patient's family.

PMID- 16974215
TI  - A meta-analysis of success rates for digit replantation.
AB  - The decision to replant a severed part is based on the numerous factors that
      influence survival of the part and the functional and aesthetic benefits gained
      from replanting. Not all amputees will benefit from or are candidates for
      replantation. The decision to proceed is therefore made by the surgeon who must
      consider the mechanism and extent of injury, the age of the patient, the presence
      of other medical or surgical conditions, the likely functional outcomes, and the
      patient's motivation to undergo a difficult procedure, which is followed by a
      lengthy recovery. This is a meta-analysis of the available studies that tracks
      the outcomes, based on 9 criteria, after the amputation of a total of 1803 digits
      in 1299 patients. By combining the data from numerous sources, a statistically
      significant picture emerges which may be used to educate patients and help guide
      the surgeon in the decision to replant.

PMID- 16974216
TI  - A new modification of trapeziectomy and soft tissue interposition arthroplasty
      with abductor pollicis longus advancement.
AB  - A new modification of trapeziectomy, soft-tissue interposition arthroplasty with
      a one-half slip of the flexor carpi radialis tendon and advancement of the
      abductor pollicis longus tendon for treatment of thumb carpometacarpal
      degenerative arthritis and instability is presented. This procedure facilitates
      tenodesis of the flexor carpi radialis slip at the first metacarpal and realigns
      and rebalances the thumb posture by using and advancing the abductor pollicis
      longus tendon. Therefore, this new modification eliminates the need for
      perioperative pin fixation of the first metacarpal, offers better soft tissue
      tenodesis of the ligament reconstruction component of the procedure, and results
      in improved intraoperative thumb alignment.

PMID- 16974217
TI  - Arthroscopic management of volar lunate facet fractures of the distal radius.
AB  - The clinical outcome of an intraarticular distal radius fracture is generally
      thought to be associated with the following factors: amount of radial deformity,
      joint congruity, and associated soft-tissue injuries. The proposed technique to
      manage this fracture pattern that involves a displaced volar lunate facet
      fragment uses wrist arthroscopy and pinning. Distraction of the fracture before
      arthroscopy is accomplished either by external fixation or by the arthroscopy
      tower. A freer elevator is introduced dorsally to disimpact the fragments, and
      next, a nerve hook is used to reduce the volar lunate facet, which is
      subsequently pinned to the radial styloid. The remaining fragments are reduced
      with interfragmentary pin fixation, and this anatomical articular construct is
      fixed to the radial metaphysis. The advantages of this technique are: (a)
      accurate assessment of articular congruency by direct visualization, (b)
      identification and repair of associated lesions, and (c) minimal soft tissue
      disruption. Potential disadvantages of external fixation supplemented by
      interfragmentary pins may be that it does not provide for rigid stable fixation,
      and therefore, does not allow for early motion compared to open reduction and
      internal fixation. Furthermore, it is technically challenging, and is therefore
      suggested as an alternative for the aforementioned fracture pattern.

PMID- 16974218
TI  - Biologic resurfacing of the glenoid using a meniscal allograft.
AB  - Biologic resurfacing of the glenoid is a treatment alternative for young patients
      who develop rapid and aggressive destruction of glenoid. In 2001, a technique was
      developed to allow secure fixation of a meniscal allograft to the glenoid in
      combination with hemi-arthroplasty replacement of the humeral head. The authors
      have modified this technique by addressing posterior wear factors, as well as
      circumferential covering of the glenoid perimeter. The meniscal horns are sutured
      together to fashion the allograft in an ovoid shape. The meniscus closely matches
      the circumference of the glenoid and therefore 180 degrees coverage of the
      glenoid rim is achieved. In addition, the wedge shape of the meniscus may enhance
      comfort and stability.

PMID- 16974219
TI  - The hypothenar fat pad transposition flap: a modified surgical technique.
AB  - The hypothenar fat pad flap has been shown to produce reliable clinical results
      for the treatment of recurrent carpal tunnel syndrome secondary to cicatricial
      tethering. The flap utilizes soft vascularized tissue that does not compromise
      hand function and is of sufficient size to provide median nerve coverage in the
      carpal tunnel. We describe technical modifications that facilitate improved,
      tension-free transposition of the pedicled fat pad flap. These modifications
      enable transfer of vascularized tissue and decrease iatrogenic damage to the
      important perforator vessels. The hypothenar fat pad transposition flap provides
      a reliable source of vascularized local tissue that can be used successfully as
      an adjunct to neurolysis for the treatment of recurrent idiopathic CTS secondary
      to perineural scarring.

PMID- 16974220
TI  - Avulsion fractures from the base of phalanges of the fingers.
AB  - Avulsion fractures of the phalanges are among challenging problems encountered in
      the hand surgery. These fractures are characterized by existence of small bone
      fragments usually attached to a collateral ligament. They mostly occur in
      metacarpophalangeal and proximal interphalangeal joints. Bony gamekeeper's thumb
      is one of the well-known. Inadequate reduction and healing of these fractures may
      lead to joint deformity, chronic instability and posttraumatic arthritis.
      Existence of very small bone fragments and involvement of joint surface are the
      obvious factors predisposing to technical problems in reposition and fixation of
      these fractures. Avulsion fractures are intraarticular according to their
      configuration and need anatomic reduction. AO principles depending on stable
      fixation and compression have difficulties to be applied to these fractures owing
      the inconvenience of the osteosynthesis materials and implants available are
      designed for fracture fixation of larger bones. Fixation may result in further
      comminution of the fragments.

PMID- 16974221
TI  - Tenodesis extension splinting for radial nerve palsy.
AB  - Injuries to the radial nerve or posterior interosseous nerve can lead to
      significant functional limitation. Inability to extend the wrist and/or digits
      prevents the hand from being positioned properly for functional tasks. Therapy
      after radial nerve injury is geared toward maintaining passive extension of the
      wrist and digits. Sensory reeducation can also be performed but often not
      necessary since the distribution of the nerve distally is on the dorsoradial
      surface of the hand. Since nerve regeneration is often a lengthy process and the
      extent of recovery is variable, splinting the involved extremity is used to
      prevent contractures and maximize function. This article introduces a new splint
      that allows patients to extend the fingers and thumb via a tenodesis effect at
      the wrist. In early trials, it has produced excellent results for enhancing
      functional use of the injured extremity while nerve regeneration occurs or until
      tendon transfers have been performed.

PMID- 16974222
TI  - A vascularized technique for bone-tissue-bone repair in scapholunate
      dissociation.
AB  - Several surgical options have been used for the repair of scapholunate
      instability over the last 50 years. The many options have included neglect,
      reduction with percutaneous pinning, primary repair, partial fusions, tendon
      weaves, and others. Recent advancements in scapholunate repair and anatomy have
      been aimed at a more physiological repair. Composite replacement of the entire
      scapholunate interval similar to other tendon repairs seen in orthopedic surgery
      has become popular. Currently, more common hand-based grafts are bone-retinaculum
      bone, third or second metacarpal-carpal bone or hamate-capitate grafts. There
      still exist some failures in the outcome after any of these procedures. This
      technique demonstrates the use of a vascularized autograft replacement on a
      pedicled graft. This procedure is the natural extension of the third or second
      metacarpal-carpal bone autograft, previously reported in the literature. The use
      of this proven graft, with a pedicle based on the intermetacarpal artery, may
      avoid some of the late complications seen with other autografts.

PMID- 16974223
TI  - Confirmatory needle placement technique for scalene muscle block in the diagnosis
      of thoracic outlet syndrome.
AB  - Scalene muscle block is often performed to assist with the clinical
      differentiation of primary sources of pain and weakness in the upper limb when
      the differential diagnosis includes thoracic outlet syndrome. This presentation
      offers a simple clinical method to assess needle placement in the scalene muscle
      before an injection of local anesthetic which, if properly placed, weakens the
      scalene muscle and often leads to temporary relief of symptoms associated with
      neurovascular compression. An appropriate scalene block response provides
      assistance with medical decision making.

PMID- 16974224
TI  - A new modification of two-stage flexor tendon reconstruction.
AB  - A new modification of 2-stage flexor tendon reconstruction is described. This new
      modification includes the utilization of the insertion of the flexor digitorum
      profundus tendon to develop a distal tunnel for initial placement of the silicon
      rod at the first stage and subsequent placement of the tendon graft at the second
      stage. This allows a more distal attachment of the tendon graft at the second
      stage of the reconstruction, to maximize tendon excursion and minimize adhesions
      to the volar plate of the distal interphalangeal joint. Therefore, this new
      modification offers better distal interphalangeal joint function and ease of
      second stage distal tendon graft attachment.

PMID- 16974225
TI  - A new surgical technique for the ligament reconstruction of the
      trapeziometacarpal joint.
AB  - Isolated traumatic dislocation of the trapeziometacarpal joint is rare compared
      with fracture-dislocation of the joint. The mechanism of injury is usually axial
      loading on a flexed thumb metacarpal, leading to dorsal dislocation of the joint.
      Closed reduction with immobilization is an acceptable method of treatment if the
      joint is stable after the reduction. Otherwise, early ligamentous reconstruction
      is recommended to reduce the likelihood of secondary arthritis. Various surgical
      techniques have been used to reestablish the ligamentous integrity of the joint;
      however, these techniques usually reconstruct only 1 or 2 ligaments around the
      joint. The current technique is aimed to reconstruct all 4 ligaments of the
      trapeziometacarpal joint using a half strip of extensor carpi radialis brevis
      tendon.

PMID- 16974226
TI  - Mini external fixation in the hand.
AB  - External fixation is an effective means of addressing several pathologies of the
      hand. The advantages of its use include the ability to achieve stable fixation,
      minimize soft tissue trauma at the site of injury, and allow wound care and
      mobilization of adjacent joints. External fixators can be constructed from
      material readily available in the operating room or obtained from a commercial
      source. Sufficient rigidity can be achieved by any of these means. Improper
      placement, although achieving rigid fixation, may compromise motion and overall
      function if basic principles of external fixation are not followed or if the
      anatomy of the hand is not taken into consideration. The objective of this
      article is to describe the technique of application of mini external fixation,
      emphasizing the basic principles of external fixation as they relate to the
      specific anatomy of the hand. In addition to fracture fixation, various other
      uses are described including distraction lengthening, arthrodesis, treatment of
      nonunion, and infection.

PMID- 16974227
TI  - Percutaneous trigger finger treatment.

PMID- 16977254
TI  - Oxidative stress explains differences in large elastic artery compliance between
      sedentary and habitually exercising postmenopausal women.
AB  - OBJECTIVE: To determine whether oxidative stress contributes to differences in
      large elastic artery compliance between sedentary and habitually exercising
      postmenopausal women. DESIGN: Carotid artery compliance was measured during acute
      intravenous infusions of saline (control) and supraphysiological doses of the
      potent antioxidant ascorbic acid (vitamin C) in sedentary (n = 15; 58 +/- 1
      years) and endurance exercise-trained (n = 11, 59 +/- 1) healthy postmenopausal
      women. RESULTS: Carotid artery compliance was 24% higher in the exercising versus
      sedentary women during control (P < 0.001). During ascorbic acid infusion,
      carotid artery compliance was increased by 28% in the sedentary women (1.29 +/-
      0.12 to 1.60 +/- 0.12 mm/mm Hg x 10, P < 0.001 vs control) but was unchanged in
      exercising women (1.60 +/- 0.14 vs 1.48 +/- 0.14 mm/mm Hg x 10, P = 0.10),
      abolishing the habitual exercise-associated baseline difference. The change in
      compliance with ascorbic acid was most strongly related to maximal aerobic
      capacity (r = -0.64, P < 0.0001) and body fatness (r = 0.60, P < 0.0001) and was
      more modestly related to oxidized low-density lipoprotein, waist circumference,
      interleukin-6, total and low-density lipoprotein cholesterol (all r = 0.40 to
      0.49, all P < 0.05), and high-density lipoprotein cholesterol (r = -0.48, P =
      0.01). Carotid artery diameter, blood pressure, and heart rate were unaffected by
      ascorbic acid. CONCLUSIONS: These results indicate that the greater large elastic
      artery compliance in habitually exercising compared with sedentary estrogen
      deficient postmenopausal women may be mediated by an absence of oxidative stress,
      perhaps related in part to more favorable cardiovascular risk factors.

PMID- 16977255
TI  - Polymorphisms in the estrogen synthesis and metabolism pathways and symptoms
      during the menopausal transition: observations from the Seattle Midlife Women's
      Health Study.
AB  - OBJECTIVE: The purpose of this study was to determine whether polymorphisms in
      the estrogen synthesis and metabolism pathways are associated with women's
      vasomotor symptom experiences during the menopausal transition. DESIGN: In 2002,
      a subset of women enrolled in the Seattle Midlife Women's Health Study since 1990
      (N = 174) provided a buccal smear for genotyping. Women were recruited by
      complete ascertainment of selected multiethnic neighborhoods in 1990.
      Participants were midlife women with a mean age of 53 years in 2005, well
      educated, employed, married, and represented a multiethnic population. Genotyping
      was done for the following polymorphisms: CYP1A1m2; CYP1B1*2 and CYP1B1*3; CYP17
      5'UTR; CYP19 3'UTR; CYP19 (TTTA)n; including CYP19 7r and CYP19 7(r-3); CYP19 8r
      and CYP19 11r; and ESR1PvuII and ESR1XbaI. Women rated their vasomotor symptom
      severity in diaries on days 5, 6, and 7 of the menstrual cycle or on a constant
      date each month for women skipping periods. Menopausal transition stage was
      determined from daily menstrual calendars. First voided urine specimens provided
      several times each year were assayed for estrone glucuronide. RESULTS: Women with
      the CYP19 11r polymorphism reported more severe and frequent hot flashes during
      the middle and late menopausal transition stages and postmenopause and higher E1G
      levels during middle and late stages. None of the other polymorphisms studied
      were related to hot flashes or to estrone glucuronide levels. CONCLUSIONS: These
      findings suggest a possible role for CYP19 polymorphisms in estrogen levels and
      in vasomotor symptoms during the menopausal transition that warrants further
      study in larger and more diverse populations of women.

PMID- 16977256
TI  - Acute insulin response (AIR): review of protocols and clinical interest in islet
      transplantation.
AB  - Various stimuli have been used in clinical practice to test islet function,
      including intravenous glucose, arginine--both at basal glucose levels and with
      the hyperglycaemic clamp, tolbutamide, glucagon and glucagon-like peptide 1. The
      subsequent first phase insulin response (also termed acute insulin response or
      AIR) to intravenous glucose or arginine has been quantified in a variety of ways,
      from the mean serum insulin measured at multiple times after glucose injection to
      the mean value above baseline of serum insulin at 2 to 10 min. The purpose of
      this study was to review the different protocols of AIR calculation and their
      pitfalls, and to assess the results of AIR in the islet transplantation field. By
      investigating the first phase of insulin secretion, AIR provides both a
      qualitative and a quantitative approach to insulin secretion. In islet
      transplantation, post-glucose AIR (AIRg) may predict graft survival while post
      arginine AIR (AIRa) may be better correlated with engrafted beta cell mass,
      despite these facts need to be confirmed. AIRa also limits intravenous
      hyperglycaemia glucotoxicity. In conclusion, AIR could help to predict the need
      for a second or third islet injection in islet transplantation. These specific
      indications, however, need to be confirmed by future studies and completed by
      other approaches such as insulin sensitivity studies and in vivo morphological
      assessment of islet mass.

PMID- 16977257
TI  - The refusal of treatment in anorexia nervosa, an ethical conflict with three
      characters: "the girl, the family and the medical profession". Discussion in a
      French legislative context.
AB  - Anorexic patients are prone to refuse treatment despite life-threatening
      complications. The therapist's ethical code can be torn between duty to protect
      life, and law that demands respect of the patient's autonomy. The age of these
      girls introduces a third participant in this ethical conflict with three
      characters: "the girl, her family and the physician". Even if her decision to
      refuse treatment can appear unreasonable, the patient suffering from anorexia
      nervosa remains "competent" to receive information concerning her state of health
      and to make up her own mind about what to do next. French law only recognises for
      the therapist a real duty to make efforts to convince the patient of the absolute
      necessity of treatment. However it appears important to confront these legal
      obligations with different situations created by the disease in order to help
      pave the way to finding medical solutions capable of conciliating the objective
      of the best treatment, the own ethical code of the physician and the respect of
      current legislation.

PMID- 16977258
TI  - Accuracy of continuous subcutaneous glucose monitoring with the GlucoDay in type
      1 diabetic patients treated by subcutaneous insulin infusion during exercise of
      low versus high intensity.
AB  - AIM: The GlucoDay allows continuous glucose monitoring by subcutaneous
      microdialysis in sedentary conditions. To validate it when glycaemia may undergo
      rapid and dramatic changes, we investigated its accuracy during two exercise
      sessions with markedly different glucose disposal rates. METHODS: Nine male
      diabetic patients, aged 32-61, treated by insulin pumps, first underwent a
      standard maximal exercise-test designed for determining the maximal oxygen
      consumption and the first ventilatory threshold (Vt1). Then two 30 min steady
      state workloads at 15% below and 15% above the Vt1 were performed in random order
      with the GlucoDay, and measurement of CHO oxidation rates was made by indirect
      calorimetry. RESULTS: CHO oxidation during exercise at +15% Vt1 was higher
      (+943.5 mg/min, ie +45.5%, P<0.01) than during exercise at -15% Vt1 No
      hypoglycaemia occurred. Due to breakages of 39% of subcutaneous probes, eleven
      steady-state sessions in 7 subjects allowed to compare 141 paired glucose (sensor
      vs. venous) determinations. The Clarke error grid situates 92.9% of glucose
      values within the A zone and 6.4% within the B zone, while only one pair of
      values (0.7%) falls in the D zone. Venous glucose tended to decrease more rapidly
      than sensor glucose during exercise. Bland-Altman plots evidence for a few cases
      of underestimation of venous glucose at high intensity. CONCLUSIONS: This study
      showed satisfactory accuracy of the GlucoDay during exercise. A slight lag time
      in sensor values likely explains a few discrepancies that do not appear as
      clinically meaningful. Reduction of probe fragility and confirmed sensor accuracy
      in hypoglycaemia would further support applicability of GlucoDay at exercise.

PMID- 16977259
TI  - Iodine status, thyroid function, thyroid volume and thyroid autoimmunity in
      patients with type 1 diabetes mellitus in an iodine-replete area.
AB  - OBJECTIVE: To analyze the prevalence and clinical significance of thyroid
      autoimmunity, thyroid volume and iodine status in patients with type 1 diabetes
      mellitus compared with age and sex matched healthy controls, in an iodine
      deficiency improved area. METHOD: Fifty-eight patients with type 1 DM, 30 female
      and 28 male, who attended the pediatric endocrinology clinic of Karadeniz
      Technical University Hospital were included into the study. They were compared
      with 58 healthy children matched for sex and age. Routine thyroid function
      parameters, thyroid autoantibodies (TPOAb, TGAb and TRAb) and urinary iodine
      excretion were measured and thyroid volume was determined by ultrasonography
      (US). RESULTS: Twenty-six patients (44.8%) in diabetic patients and 20 subjects
      (34.5%) in the control group had thyroid autoantibody positivity. TPOAb and TGAb
      positivity were significantly high in diabetic patients (P=0.01 and P=0.032,
      respectively). Thyroid US revealed a thyroid volume of 6.6+/-3.5 ml (median 6.4
      ml, range 1.117.2 ml) in the diabetic patients compared with 3.7+/-2 ml (median
      3.1 ml, range 0.8-8.6 ml) in the control group (P=0.0001). Median urinary iodine
      levels of both groups were clearly above the threshold level for iodine
      deficiency, but 26 patients with type 1 DM (44.8%) and 16 controls (27.5%) had
      urinary iodine excretion below 100 microg/L, and 21 (36.2%) of diabetic patients
      and two subjects (3.4%) of the control group were consistent with severe iodine
      deficiency. No significant differences were noted in diabetic patients in terms
      of age, duration and metabolic control of the disease and thyroid volume when
      compared according to the autoantibody presence. Additionally, there were no
      significant differences between the iodine deficient and iodine sufficient
      diabetic patients in terms of age, sex, duration of disease, HbA1c, thyroid
      hormones and thyroid volumes. Thyroid autoimmunity was lower in patients with
      iodine deficiency (38.4% vs. 50%), but not statistically significant. CONCLUSION:
      We found that type 1 DM patients had larger thyroid volume compared with healthy
      control groups, and a large portion of them had the markers of autoimmune thyroid
      disease and iodine deficiency. Surprisingly, we found that a large portion of the
      healthy children had TRAb positivity. We proposed that TRAb must be considered in
      community surveys or prevalence studies of autoimmune thyroid disorders in iodine
      replete areas. Additionally, prospective longitudinal studies are needed to
      determine the clinical significance of TRAb positivity in diabetic patients.

PMID- 16977261
TI  - Metabolic syndrome components in Indian migrants with type 2 diabetes. A matched
      comparative study.
AB  - OBJECTIVE: To study the metabolic syndrome (MS) in Indian subjects with type 2
      diabetes (T2D) in comparing them with controls from the Indian community and from
      the general population. METHOD: An adapted definition of MS by the Third report
      of the National Cholesterol Education Program's Adult Treatment Panel III was
      used. We defined three groups matched for sex and age (+/-5 years). Non
      parametric tests for comparison of matched samples and conditional logistic
      regression were used. RESULTS: We selected 71 Indians with T2D (group 1) and two
      control groups with fasting blood glucose<6.1 mmol/L: 71 Indians (group 2) and
      213 subjects from the general population (group 3). Patients were 24 to 76 years
      old and each group contained 56% men. Globally, MS was identified in 77% of the
      group 1 when diabetes was taken into account. When diabetes was excluded there
      were 47% of MS in group 1, 18% in group 2 and 16% in group 3. The clusters of
      four factors (hypertension, large waist circumference, hypertriglyceridemia and
      Low HDL-C) were more common in Indians. The most frequent factors were
      hypertriglyceridemia and large waist circumference in Indians. Indians with T2D
      had a 5-fold higher risk of MS than the general population group, OR (95% CI):
      4.93 (2.71 - 8.97); P<0.001. CONCLUSION: The high frequency of MS and of
      hypertriglyceridemia in Indians with T2D highlights the need for screening and
      management of MS in this population facing a high cardiovascular risk.

PMID- 16977260
TI  - Modulation of the production of reactive oxygen species (ROS) by cAMP-elevating
      agents in granulocytes from diabetic patients: an Akt/PKB-dependent phenomenon.
AB  - BACKGROUND: Granulocytes from healthy subjects and from patients suffering from
      diabetes mellitus present differences in reactivity to stimulation with cyclic
      nucleotide-elevating agents. The production of reactive oxygen species (ROS) is
      inhibited in cells from non-diabetic subjects following such stimulation, but
      activated through a PKA-independent signaling pathway in granulocytes from type 1
      and type 2 diabetic patients. The aim of the present study was to understand
      better the changes in signaling mechanisms induced by the disease. METHODS: ROS
      production in granulocytes from healthy subjects and from type 1 and type 2
      diabetic patients was measured using a luminol-dependent chemiluminescence assay.
      Granulocytes were stimulated by the addition of the cAMP-elevating agent
      dibutyryl cAMP. In some experiments, granulocytes were pre-treated with an
      inhibitor of PKA or Akt/PKB prior to cAMP stimulation. RESULTS: Intracellular
      elevation of cAMP induced a PKA-dependent and Akt/PKB-independent inhibition of
      ROS production in granulocytes from healthy subjects, but a significant
      activation in cells from both type 1 and type 2 diabetic patients. Most
      significantly, activation of ROS generation in cells from diabetic patients was
      shown to be Akt/PKB-dependent and PKA-independent. CONCLUSIONS: These results
      suggest that chronic hyperglycaemia could induce metabolic adaptation in cAMP
      related signaling mechanisms. Epac (exchange protein directly activated by cAMP)
      is a novel cAMP receptor besides PKA involved in different signaling pathways.
      The cAMP-stimulated inverse ROS response in granulocytes from type 1 and type 2
      diabetic patients may be due to a change in signaling pathways from cAMP/PKA to
      cAMP/Epac/Akt/PKB. These preliminary results require further studies in order to
      evaluate their consequences on innate immunity and pathogenesis of diabetes
      mellitus.

PMID- 16977262
TI  - Gliclazide treatment lowers serum ICAM-1 levels in poorly controlled type 2
      diabetic patients.
AB  - OBJECTIVE: To investigate the potential effect of gliclazide on serum ICAM-1
      (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule
      1) levels in poorly controlled type 2 diabetic patients. PATIENTS AND METHODS:
      The study included 104 patients, randomly divided into two groups. Group A
      comprised 53 patients (26 men) treated with gliclazide with a mean age of 67.5+/
      9.9 years, a mean diabetes duration of 13.4+/-5.4 years and a mean HbA1c of 8.6+/
      1.1%. Group B comprised 51 patients (25 men) treated with glibenclamide with a
      mean age of 66.4+/-10.9 years, a mean diabetes duration of 13.2+/-6.1 years and a
      mean HbA1c of 8.4+/-1.3%. A third group of 30 healthy controls (15 men) with a
      mean age of 63.3+/-10.4 years was also included. Serum levels of ICAM-1 and VCAM
      1 were measured at the beginning of the study and after six months of treatment.
      RESULTS: Pretreatment serum ICAM-1 and VCAM-1 levels did not differ between
      groups A and B, while they were significantly higher (P=0.0001) than in healthy
      controls. No significant difference in HbA1c, body mass index, blood pressure
      control and lipid profile between the two groups was observed after the sixth
      month of treatment. In group A, serum ICAM-1 levels after six months of treatment
      were significantly reduced from 623.12+/-61.17 ng/ml to 370.14+/-49.92 ng/ml
      (P=0,01), while no reduction was found in VCAM-1 levels. In group B, no reduction
      was found in serum ICAM-1 and VCAM-1 levels after the end of the study.
      CONCLUSIONS: Our results suggest that gliclazide treatment reduces serum ICAM-1
      levels in poorly controlled type 2 diabetic patients. This reduction is
      independent of the hypoglycaemic action of gliclazide.

PMID- 16977263
TI  - Efficacy of short term continuous subcutaneous insulin lispro versus continuous
      intravenous regular insulin in poorly controlled, hospitalized, type 2 diabetic
      patients.
AB  - Intravenous insulin infusion (IVII) is rapidly effective in improving glycaemia
      in uncontrolled hospitalized diabetic patients. This significantly improves their
      morbidity and mortality. Intravenous insulin infusion may lead to IV infusion
      complications and is a heavy burden for caregivers. AIM: The aim of our work was
      to compare the efficacy of IV regular insulin versus lispro Continuous
      Subcutaneous Insulin Infusion (CSII), in improving glycaemia in patients
      hospitalized for uncontrolled type 2 diabetes, the efficacy being assessed on the
      average blood glucose level observed. METHODS: The study was designed as a
      prospective randomized study. Thirty-three type 2 diabetic patients, hospitalized
      for uncontrolled diabetes by their usual practitioner were included. After
      acceptation, patients were randomly assigned to lispro CSII (group 1, n=20) or
      IVII regular insulin (group 2, n=13) for 5 days. Ten capillary blood glucose/day
      were performed. Pre-meal blood glucose targets were 4.4-6.6 mmol/l. Mann Whitney,
      Wilcoxon and Fischer exact tests were used. RESULTS: BG levels decreased
      significantly (-3.4+/-0.55 mmol/l in group 1 and -3.60+/-0.55 mmol/l in group 2,
      P<0.01) during the first 12 hours. Mean daily blood glucose at day 5 was
      statistically improved in both groups compared to day 1 (P<0.05 Wilcoxon) and
      comparable between the 2 groups. No severe hypoglycaemia was reported. No
      catheter complications occurred in group 1, 7 occurred in group 2. CONCLUSION:
      CSII and IVII infusion were comparable in rapidly improving hyperglycaemia in
      uncontrolled type 2 diabetic patients. CSII, being more convenient, could be
      preferred in medical and surgical settings.

PMID- 16977264
TI  - Effect of dietary calcium intake on weight gain in type 2 diabetic patients
      following initiation of insulin therapy.
AB  - OBJECTIVES: This pilot study analyses weight gain in type 2 diabetic patients at
      initiation of insulin therapy, according to daily calcium intake. METHODS: Type 2
      diabetic patients consecutively admitted for initiation of insulin therapy were
      studied between January and March 2004 in a monocenter study. Dietary intake was
      assessed by a 7-day food history before insulin treatment (initial visit) and 4
      to 6 months later (final visit). RESULTS: Thirty-one patients were studied (18
      males and 13 females; mean age 62+/-9 years, with diabetes duration 14+/-10
      years). Weight significantly increased between initial and final visits (81.9+/
      16.2 vs. 84.8+/-17.8 kg; P=0.0272). Median weight gain was 2.4 kg (IQR: -1.15 to
      +5.27 kg). Waist circumference increased by 2 cm (IQR: 0 to +4 cm). There was no
      difference between weight change and tertile of calcium intake adjusted on energy
      intake. We did not find any correlation between weight change and total calcium
      intake (Rho=0.186; P=0.3165) or dairy calcium intake (Rho=0191; P=0.3040).
      Similarly, we did not find any correlation between waist circumference change and
      total calcium intake (Rho=0.324; P=0.1205) or dairy calcium intake (Rho=0.285;
      P=0.0755). CONCLUSION: We found no relation between total or dairy calcium intake
      and weight change during initiation of insulin therapy in type 2 diabetic
      patients. Dietary calcium intake does probably not play a major role on insulin
      induced body weight gain.

PMID- 16977265
TI  - Elevation of CKP induced by ezetimibe in monotherapy: report on two cases.
AB  - Few cases of myopathy have been reported in patients treated with ezetimibe as
      monotherapy or in association with a statin. We report on two cases of elevation
      of CKP that occurred upon monotherapy with ezetimibe, which were reversible after
      discontinuation of the drug. In both cases, patients previously experienced
      intolerance with other lipid-lowering agents. The pathogenesis of muscle toxicity
      associated with ezetimibe is not known yet. An interaction with statin or a
      toxicity mechanism common to several lipid-lowering drugs have been suggested. A
      potential role of induction of glucuronidation by numerous associated drugs can
      also be involved Although association of ezetimibe with myopathy seems to be
      uncommon, special attention should be given to patients treated with ezetimibe
      who had a previous intolerance to other lipid-lowering drugs and who received
      several drugs.

PMID- 16977267
TI  - From patient education for therapeutic failure to the failure of patient
      education.

PMID- 16977266
TI  - How to better systematize the diagnosis of neuropathy?
AB  - Two attitudes can be proposed, one consisting of making a diagnosis of
      neuropathy, the other seeking to grade the stage that it has reached in order to
      give a prognosis and above all determine the right way in which to educate the
      patient. In order to do this, it is important for the diagnosis to be thorough.
      It should be based both on listening to what the patient has to say and examining
      him/her. It is vital to listen to the patient because the warning signs are
      discreet, yet very evocative, and they will be a great help in making a positive
      diagnosis. They should not be confused with signs of arterial damage. They should
      then be interpreted by means of clinical examination and the tools that are
      available, i.e. essentially monitoring the osteo-tendinous reflexes and sensory
      signs. The sensory signs can only be studied with high-quality instruments, i.e.
      either a monofilament of proven technical quality and that should be used with
      care in line with good clinical practice recommendations, or by using a graduated
      tuning fork, or a neuroesthesiometer which will make it possible to obtained
      graduated responses, not simply binary responses of the "yes/no" variety. A whole
      series of scores have been put forward combining both functional and physical
      signs, making it possible to try to quantify the stage reached and the extent of
      the neuropathy. It is only by using a thorough and regularly applied routine that
      we can progress to establishing a better prognosis and providing a better
      educational service for the patient.

PMID- 16977268
TI  - Should diabetic patients be asked to test their blood glucose 90 to 120 minutes
      after the beginning of their meals?
AB  - There are three distinct objectives in reducing the post-prandial blood glucose
      peaks: 1st to reduce the risk of foetal macrosomia in pregnancy, 2nd to reduce
      cardiovascular morbi-mortality, 3rd to lower the HbA1c. With 6-7 glycaemic
      controls per day and fractionning their meals, motivated women with gestational
      diabetes reach this goal. But there is no data today directly proving that post
      prandial glycaemia is specifically related to the development of micro and
      macrovascular complications. So to reduce the cardiovascular risk, there are more
      arguments in favour of lowering HbA1c or prescribing statins than in prescribing
      a hypoglycaemic drug acting selectively on post-prandial glycaemia. Lastly, to
      reduce HbA1c near to the goal of 7%, the most important is to reduce the
      preprandial glycaemia below 1.20 g/l. The patients must be required to monitor
      their post-prandial glycaemia 2 hours after the beginning of the meal only when
      the aim is to lower the HbA1c below 7% or 6.5%, for example during pregnancy, or
      in case of discrepancy between glycaemia at 8 a.m. and 7 p.m. (below 1.20 g/)l
      and HbA1c (above 7%). In other cases, in type 2 diabetes, two glycaemias per day,
      fasting and vesperal, seems sufficient.

PMID- 16977269
TI  - Breast biopsies. Diagnosing abnormalities found on exam, imaging.

PMID- 16977270
TI  - Raloxifene works as well as tamoxifen in preventing invasive breast cancer.

PMID- 16977271
TI  - First cervical cancer vaccine wins approval, promises significant benefits.

PMID- 16977272
TI  - Before and after weight-loss surgery. Staying committed to a healthy you.

PMID- 16977274
TI  - Pneumonia vaccine. A shot that can save lives.

PMID- 16977276
TI  - Good and bad guilt. And what to do about these feelings.

PMID- 16977275
TI  - Mayo Clinic office visit. Reducing breast cancer risk. An interview with Sandhya
      Pruthi, M.D.

PMID- 16977277
TI  - Can wearing acrylic nails harm your natural nails?

PMID- 16977278
TI  - Is it safe to try new drugs when they first come on the market?

PMID- 16977279
TI  - I heard on the news that calcium supplements don't provide a significant benefit
      to bone strength. Should I stop taking my calcium pill?

PMID- 16977280
TI  - A human papillomavirus vaccine.
AB  - A recombinant quadrivalent human-papillomavirus-like particle vaccine, Gardasil
      (Merck), has been approved by the FDA for use in girls and women 9-26 years old
      to prevent diseases associated with infection with human papillomavirus (HPV)
      types 6, 11, 16, and 18, including genital warts, precancerous cervical, vaginal
      or vulvar lesions, and cervical cancer.

PMID- 16977281
TI  - Varenicline (Chantix) for tobacco dependence.

PMID- 16977282
TI  - Intravenous ibandronate (Boniva).

PMID- 16977283
TI  - VariZIG for prophylaxis after exposure to varicella.

PMID- 16977284
TI  - Automated external defibrillators.

PMID- 16977285
TI  - Herpes zoster vaccine (Zostavax).
AB  - A live attenuated varicella-zoster vaccine (Zostavax--Merck) has been approved by
      the FDA for prevention of herpes zoster (HZ; zoster; shingles) in persons > or =
      60 years old. Each dose of Zostavax contains about 14 times as much varicella
      zoster virus (VZV) as Varivax, which has been used in the US since 1995 to
      vaccinate against varicella (chicken pox).

PMID- 16977286
TI  - Darunavir (Prezista) for HIV infection.
AB  - Darunavir (Prezista--Tibotec), a new protease inhibitor, has received accelerated
      approval from the FDA for use in combination therapy of human-immunodeficiency
      virus (HIV) infection in previously treated adults. It is coadministered with low
      dose ritonavir (Norvir), which increases its bioavailability.

PMID- 16977287
TI  - Atorvastatin for stroke prevention.

PMID- 16977288
TI  - Plan B OTC.

PMID- 16977289
TI  - Natalizumab (Tysabri) returns.

PMID- 16977290
TI  - An appropriate esophagectomy for esophageal cancer: a lack of evidence and a
      growing disparity between Western and Eastern standards.

PMID- 16977291
TI  - Clinical aspects of multimodality therapy for resectable locoregional esophageal
      cancer.
AB  - Radical resection has been considered the only possible way to save the lives of
      patients with esophageal cancer. Therefore, tremendous efforts have been made in
      order to improve the surgical results for resectable locoregional esophageal
      cancer. Various surgical approaches have been developed. Combination therapies
      such as neoadjuvant, adjuvant chemotherapy, and neoadjuvant chemoradiation have
      been extensively investigated in numerous randomized clinical trials. Due to
      insufficient surgical results and high postoperative mortality rates, definitive
      chemoradiation has been studied as alternative treatment in selected patients,
      based on the concept that combined-modality therapy allows simultaneous treatment
      of locoregional disease and systemic micrometastases. Chemoradiation has shown
      survival rates equivalent to surgery in some non-randomized comparative studies.
      Presently, concerns appear to be shifting to the question of whether definitive
      chemoradiation could be an alternative to surgery in the primary treatment of
      resectable locoregional esophageal cancer. Recently, 2 randomized trials,
      comparing definitive chemoradiation with chemoradiation and surgery were
      published. These trials seem to show at first glance that definitive
      chemoradiation can achieve results comparable to surgery with neoadjuvant
      chemoradiation. More sophisticated trials should be conducted as treatment
      modalities used in these trials are far from routine.

PMID- 16977292
TI  - The use of a water seal to manage air leaks after a pulmonary lobectomy: a
      retrospective study.
AB  - BACKGROUND: The methods for managing chest drainage tubes during the
      postoperative period differ among thoracic surgeons and, as a result, the optimal
      method remains controversial. PATIENTS AND METHODS: We reviewed 170 consecutive
      patients undergoing a pulmonary lobectomy for either primary lung cancer or
      metastatic lung cancer from January 1998 to December 2002. After the operation,
      the chest drainage tube was placed on a suction pump with a negative pressure of 
      10 cmH(2)O in 120 patients before 2001, while such drainage tubes were kept on
      water seal in 47 cases mainly since 2001. RESULTS: Regarding the preoperative and
      postoperative variables, postoperative air leak as well as the video-assisted
      thoracic surgery (VATS) procedure were more frequently observed in the water seal
      group than in the suction group (p=0.01580, p<0.001, respectively). In comparing
      these different populations, each Kaplan-Meier curve, which presented the
      duration of the postoperative air leak seemed to be similar between the two
      methods. CONCLUSION: These observations suggest that applying chest tubes on
      water seal seems to be an effective method for preventing postoperative air leak
      in clinical practice. However, a prospective randomized trial using a larger
      series of patients is warranted for this subject.

PMID- 16977293
TI  - Thoracoscopic pleural biopsy for tuberculous pleurisy under local anesthesia.
AB  - OBJECTIVE: We directly examined the thoracic cavity by thoracoscopy under local
      anesthesia, performed pleural biopsy, and made a definitive pathological
      diagnosis in tuberculous pleurisy. SUBJECTS AND METHODS: We performed a
      retrospective study of 32 patients who had been bacteriologically and
      pathologically diagnosed with tuberculous pleurisy by thoracoscopy under local
      anesthesia in our hospital between January 1995 and November 2004. RESULTS:
      Bacteriological examination of pleural fluids obtained by thoracentesis before
      examination showed that one sample was polymerase chain reaction (PCR)-positive,
      and 5 samples were culture-positive. Bacteriological examination of pleural
      fluids obtained by thoracoscopy revealed that 2 samples were PCR-positive, and 5
      samples culture-positive, including 2 preoperatively positive samples. The
      adenosine deaminase (ADA) levels ranged from 18.3 to 279.0 U/L, with a mean of
      72.9 U/L, including 50 U/L or less in 5 patients and 35 U/L or less in 3
      patients. Thirty patients (93.8%) were successfully diagnosed by pleural biopsy
      with pathological examination, and 21 (65.6%) of them by pathological examination
      alone. CONCLUSION: In patients with suspected tuberculous pleurisy, thoracoscopic
      pleural biopsy under local anesthesia should be actively performed, because the
      technique has a high diagnostic rate, and can be easily and safely performed.

PMID- 16977294
TI  - 40 Years experience in mitral valve replacement using Starr-Edwards, St. Jude
      Medical and ATS valves.
AB  - BACKGROUND: We have used the Starr-Edwards ball (S-E) valve since 1963, the St.
      Jude Medical (SJM) valve since 1978, and the ATS valve, since 1993 as the first
      choice of mechanical valve. In this study, the results with each valve during the
      40 years were investigated in single mitral valve replacement (MVR) cases.
      PATIENTS AND METHODS: The mean age for S-E valves was 32.8+/-11.1 years old
      (y.o.), for SJM it was 47.2+/-12.6 y.o. and for ATS it was 56.3+/-11.4 y.o.,
      indicating the aging of patients over time. The operative mortality decreased
      over the same time from 10.3% to 5.2% then 1.4% respectively. A significant
      difference was observed among the 3 groups with regards to the valve-related
      complication-free rate and cardiac event-free rate. However, there was no
      significant difference among the 3 groups with the other complications.
      CONCLUSION: Although there are many cases of valve-related complications with S-E
      valves, they have a role as an initial stage mechanical valve. In view of the
      long-term results extending over 20 years, the SJM valves is considered as the
      most reliable valve. The ATS valve is expected to achieve favorable results in
      the future because it may improve the quality of life (QOL) of patients and
      produce fewer valve-related complications.

PMID- 16977295
TI  - Perioperative and mid-term results of coronary bypass surgery in patients
      undergoing chronic dialysis.
AB  - PURPOSE: The goal of this study was to evaluate perioperative and mid-term
      results of coronary artery bypass grafting (CABG) in patients with end-stage
      renal disease (ESRD). METHODS: Thirty-five consecutive dialysis patients who
      required CABG over a 5-year period were investigated retrospectively. RESULTS:
      Mean patient age was 62.5+/-11.5 years. The mean number of diseased vessels was
      2.3W0.8. Off-pump CABG (OPCAB) was performed in 12 patients. The mean number of
      anastomoses per patient was 2.5+/-1.1. The perioperative mortality was 5.7%, and
      the average duration of hospitalization was 25.3+/-13.4 days. Overall 5-year
      survival rates were 63.7%. The cardiac-related 5-year survival rate was 89.3%,
      and the cardiac event-free rate was 51.7%. Multivariate analysis failed to
      identify any significant prognosticators for perioperative or long-term outcomes.
      The morbidity rate was significantly lower in patients undergoing OPCAB than in
      patients undergoing conventional CABG (8.3 vs. 47.8%; p=0.03). Perioperative
      mortality in the OPCAB group was 0%, and the average duration of hospitalization
      was shorter in the OPCAB group than in the conventional CABG group (19.7 days vs.
      28.5 days; p=0.1). CONCLUSION: In the context of coronary artery bypass surgery,
      OPCAB produced better outcomes than conventional CABG procedure in patients
      undergoing chronic dialysis. Further-more, OPCAB procedure seems to offer a
      greater benefit to dialysis patients than non-dialysis patients.

PMID- 16977296
TI  - Obstructive subglottic granuloma after removal of a minitracheostomy tube.
AB  - We report herein a patient with subglottic granuloma after removal of a
      minitracheostomy tube (Minitrach II, SIMS Portex Inc., Hythe, Kent, UK). The
      patient underwent pulmonary resection for lung cancer followed by insertion of
      the minitracheostomy tube for prevention of sputum retention. The tube was
      removed 4 days after insertion. Twelve weeks later, the patient developed severe
      dyspnea and stridor. Bronchoscopy showed an obstructive subglottic granuloma
      arising from the anterior wall. The granuloma was removed by coring out using a
      conventional tracheal tube, followed by local injection of methylprednisolone
      acetate. The patient is now asymptomatic without regrowth of the granulation
      tissue 12 weeks after the treatment. With complication in mind, attention should
      be paid to patients suffering dyspnea or stridor after removal of a
      minitracheostomy tube.

PMID- 16977297
TI  - A case of aspergilloma detected after surgery for pneumothorax.
AB  - We report a case of aspergilloma in an 80-year-old male patient who had no
      identifiable underlying disease before surgery for pneumothorax. He was
      hospitalized for left pneumothorax. A chest CT revealed a large bulla in the left
      lung apex with a nodule (diameter; 1.5 cm) at the edge of the bulla. After
      thoracodocesis, air leakage persisted and a large bulla and nodule were resected.
      Aspergillus was detected histopathologically in the nodule. Treatment with
      itraconazole 200 mg a day followed, and 4 months later he had no recurrent
      pneumothorax or Aspergillus infection.

PMID- 16977298
TI  - Adamkiewicz artery demonstrated by MRA for operated posterior mediastinal tumors.
AB  - In the thoracolumbar region, it is well known that the great anterior medullary
      artery (the artery of Adamkiewicz: AKA) is the dominant feeder of the spinal
      cord. During surgery for posterior mediastinal tumor adjacent to the lower
      thoracic aorta, perioperative distortion of the spinal cord blood supply could
      lead to neurological complication. To avoid postoperative paralysis, it would be
      useful to know the level of the intercostal artery from which the AKA originates.
      Recently, we have attempted to identify the AKA preoperatively using magnetic
      resonance angiography (MRA).

PMID- 16977299
TI  - Mucoepidermoid carcinoma of the thymus treated by multimodality therapy: a case
      report.
AB  - A case report of mucoepidermoid carcinoma of the thymus, aggressively treated by
      multimodality therapy including surgery, radiotherapy, chemothermotherapy, and
      systemic chemotherapy is presented. The patient, a 53-year-old man, underwent
      potentially complete resection for an anterior mediastinal tumor, histologically
      diagnosed as a mucoepidermoid carcinoma of the thymus with Masaoka stage II
      disease. However, because of local recurrences in the left chest wall and pleura,
      re-resection was twice performed 4 years and 5 months, and 5 years and 7 months
      after the initial surgery, in combination with intrathoracic chemothermotherapy
      and irradiation. Seven years and 1 month after the initial operation, in vitro
      chemosensitive test based-chemotherapy using vinorelbine for pleural disease was
      performed, resulting in maintenance of good quality of life (QOL) due to dramatic
      decrease in pleural effusion. He died of tumor progression, 7 years and 9 months
      after the initial treatment. Although the clinical aspects of thymic
      mucoepidermoid carcinoma are little known, it is assumed that such aggressive
      therapeutic multimodalities as repeated surgical resection, irradiation and
      chemothermotherapy, and chemotherapy based on in vitro chemosensitivity tests
      contributed to long-term survival for this unusual disease.

PMID- 16977300
TI  - Surgically removed thoracolithiasis: report of two cases.
AB  - Thoracolithiasis is a rare condition with only 12 cases of surgically removed
      nodules reported in the literature. We report 2 additional cases. Case 1: A 19
      year-old male admitted with an abnormal shadow on a chest X-ray. Computed
      tomography (CT) revealed a nodule in the right lower lung lobe. The material
      extirpated by thoracoscopy was milky white, glossy, and 1.6 cm in diameter.
      Histopathologically, it consisted of fatty necrotic tissue covered with
      hyalinized fibrous tissue. Case 2: A 78-year-old female, with a past history of
      breast cancer, admitted with an abnormal shadow on chest X-ray. CT revealed a
      nodule in the left lung S(1+2) segment, of which transbronchial biopsy findings
      indicated primary lung adenocarcinoma. Exploratory thoracoscopy incidentally
      revealed some pearly material, 0.4 cm in diameter, in the thoracic cavity. They
      were extirpated during left upper lobectomy for lung cancer; all of them
      demonstrated concentric hyalinized fibrous tissue. Thoracic surgeons should
      consider this condition in the differential diagnosis of a peripheral pulmonary
      nodule.

PMID- 16977302
TI  - Successful aortic valve replacement for infective endocarditis in a patient with
      severe liver cirrhosis.
AB  - Patients with liver cirrhosis are prone to the development of severe
      complications associated with high mortality rates after major surgery,
      especially cardiac surgery using cardiopulmonary bypass (CPB). We report the case
      of a 65-year-old man with acute infective endocarditis and aortic valve
      perforation, complicated by non-cardiac liver cirrhosis (Child-Pugh class B).
      After careful preoperative anti-inflammatory and systemic support treatment, we
      successfully treated infective endocarditis-induced aortic valve perforation by
      performing aortic valve replacement (AVR).

PMID- 16977301
TI  - Metastatic thoracic lymph node carcinoma of unknown origin on which we performed
      two kinds of immunohistochemical examinations.
AB  - Metastatic cancers of the thoracic lymph nodes without primary sites are rare.
      Such cancers are difficult for clinicians to manage as identifying the primary
      sites is difficult in using routine histologic examinations alone. We searched
      for the site of the primary lesion using immunohistochemical exploration of
      cytokeratin (CK) and thyroid transcription factors 1 (TTF-1), and 2-[18F] and
      fluorodeoxyglucose positron emission tomography (FDG PET) in a patient with
      cancer of the hilar lymph node without any known primary site. To our knowledge,
      there are no previous similar reports. A 45-year-old man presenting with a tumor
      in the right hilar region, underwent surgical resection of the tumor, resulting
      in a diagnosis of metastatic cancer of the bronchopulmonary lymph nodes. An
      immunohistochemical examination revealed the neoplastic lesion to be positive for
      CK7, negative for CK20, and negative for TTF-1. Repeated searches to identify the
      site of the primary lesion by FDG PET over the 35 months since operation have
      failed to locate a primary site.

PMID- 16977303
TI  - Intravalvular implantation technique for a modified Bentall's procedure in
      aortitis syndrome.
AB  - Surgical treatments of aortic root involvement in aortitis syndrome are
      frequently complicated by valve detachment and pseudoaneurysmal formation during
      active inflammation. A 40-year-old woman with aortitis syndrome complicating the
      ascending aortic aneurysm, severe aortic regurgitation (AR), and left coronary
      ostial stenosis was successfully treated by aortic root replacement and
      concomitant coronary artery bypass grafting (CABG) during acute inflammation. We
      devised an intravalvular implantation between the fragile aortic annulus and
      Teflon felt to a modified Bentall's procedure, which prevented anastomotic
      leakage and pseudoaneurysmal formation in the late period.

PMID- 16977304
TI  - Successful surgical repair of delayed chronic type a dissection after previous
      coronary artery bypass grafting.
AB  - This reports a case of a 68-year-old woman who had undergone coronary artery
      bypass 5 years previously. Magnetic resonance angiography (MRA) revealed that the
      ascending aorta was dilated to about 8 cm in diameter, with type A dissection,
      and with a patent left internal thoracic artery (LITA) graft to the left anterior
      descending artery (LAD). Angiography at the ascending aorta did not reveal a
      coronary artery, nor did it show the sequential saphenous vein graft (SVG) to the
      obtuse marginal and posterolateral branches. Although the risk of surgical
      treatment via repeat median sternotomy was very high, we successfully performed
      the reoperation using profound hypothermic circulatory arrest. The dissection in
      the mediastinum was facilitated by a sternum retractor for ITA-graft dissection,
      intraoperative surface echocardiography, and ultrasonic scalpel, with a widely
      opened bilateral pleural cavity. Furthermore, assuming that most of the
      myocardium was maintained by perfusion from the in-situ, patent, ITA graft, it
      was thought that cardioplegia was not necessary during profound hypothermic
      circulation.

PMID- 16977305
TI  - A non-operative survival case of an 84-year-old patient with type A acute aortic
      dissection complicated by pulseless tamponade.
AB  - An 84-year-old woman was hospitalized in hemodynamic shock due to type A acute
      aortic dissection (AAD) complicated by pulseless tamponade. She was treated
      conservatively as her family refused emergency surgery. In spite of warning her
      family that lack of intervention may possibly lead to an early death, she
      gradually improved and went home without any further problems. Emergency surgery
      for octogenarians remains controversial, however. We report the first surviving,
      non-operative case of an octogenarian with pulseless shock due to aortic
      dissection.

PMID- 16977306
TI  - Chronic contained rupture of an abdominal aortic aneurysm with vertebral erosion:
      report of a case.
AB  - A 73-year-old man had lumbago of unknown cause for several months prior to
      presentation. At examination prior to surgery for gastric cancer, an abdominal
      aortic aneurysm (AAA) of 6 cm in maximum diameter, retroperitoneal hematoma and
      vertebral erosion were found on abdominal computed tomography (CT). Hematological
      examination revealed mild anemia and stable hemodynamics. A diagnosis of chronic
      contained rupture of an AAA was made and knitted Dacron bifurcated graft
      replacement was performed. When an intraluminal thrombosis at the posterior wall
      was removed, a punched-out defect (3 x 2 cm) was discovered. When the old
      hematoma was removed, a destroyed vertebral body was found. After surgery, the
      lumbago was alleviated. The patient was transferred to the Department of Surgery
      and a gastrectomy was performed. The patient's postoperative course was
      uneventful.

PMID- 16977308
TI  - The regulator of the F1 motor: inhibition of rotation of cyanobacterial F1-ATPase
      by the epsilon subunit.
AB  - The chloroplast-type F(1) ATPase is the key enzyme of energy conversion in
      chloroplasts, and is regulated by the endogenous inhibitor epsilon, tightly bound
      ADP, the membrane potential and the redox state of the gamma subunit. In order to
      understand the molecular mechanism of epsilon inhibition, we constructed an
      expression system for the alpha(3)beta(3)gamma subcomplex in thermophilic
      cyanobacteria allowing thorough investigation of epsilon inhibition. epsilon
      Inhibition was found to be ATP-independent, and different to that observed for
      bacterial F(1)-ATPase. The role of the additional region on the gamma subunit of
      chloroplast-type F(1)-ATPase in epsilon inhibition was also determined. By single
      molecule rotation analysis, we succeeded in assigning the pausing angular
      position of gamma in epsilon inhibition, which was found to be identical to that
      observed for ATP hydrolysis, product release and ADP inhibition, but distinctly
      different from the waiting position for ATP binding. These results suggest that
      the epsilon subunit of chloroplast-type ATP synthase plays an important regulator
      for the rotary motor enzyme, thus preventing wasteful ATP hydrolysis.

PMID- 16977309
TI  - A PACS-1, GGA3 and CK2 complex regulates CI-MPR trafficking.
AB  - The cation-independent mannose-6-phosphate receptor (CI-MPR) follows a highly
      regulated sorting itinerary to deliver hydrolases from the trans-Golgi network
      (TGN) to lysosomes. Cycling of CI-MPR between the TGN and early endosomes is
      mediated by GGA3, which directs TGN export, and PACS-1, which directs endosome-to
      TGN retrieval. Despite executing opposing sorting steps, GGA3 and PACS-1 bind to
      an overlapping CI-MPR trafficking motif and their sorting activity is controlled
      by the CK2 phosphorylation of their respective autoregulatory domains. However,
      how CK2 coordinates these opposing roles is unknown. We report a CK2-activated
      phosphorylation cascade controlling PACS-1- and GGA3-mediated CI-MPR sorting.
      PACS-1 links GGA3 to CK2, forming a multimeric complex required for CI-MPR
      sorting. PACS-1-bound CK2 stimulates GGA3 phosphorylation, releasing GGA3 from CI
      MPR and early endosomes. Bound CK2 also phosphorylates PACS-1Ser(278), promoting
      binding of PACS-1 to CI-MPR to retrieve the receptor to the TGN. Our results
      identify a CK2-controlled cascade regulating hydrolase trafficking and sorting of
      itinerant proteins in the TGN/endosomal system.

PMID- 16977310
TI  - Structure and function of Tim14 and Tim16, the J and J-like components of the
      mitochondrial protein import motor.
AB  - The import motor of the mitochondrial translocase of the inner membrane (TIM23)
      mediates the ATP-dependent translocation of preproteins into the mitochondrial
      matrix by cycles of binding to and release from mtHsp70. An essential step of
      this process is the stimulation of the ATPase activity of mtHsp70 performed by
      the J cochaperone Tim14. Tim14 forms a complex with the J-like protein Tim16. The
      crystal structure of this complex shows that the conserved domains of the two
      proteins have virtually identical folds but completely different surfaces
      enabling them to perform different functions. The Tim14-Tim16 dimer reveals a
      previously undescribed arrangement of J and J-like domains. Mutations that
      destroy the complex between Tim14 and Tim16 are lethal demonstrating that complex
      formation is an essential requirement for the viability of cells. We further
      demonstrate tight regulation of the cochaperone activity of Tim14 by Tim16. The
      first crystal structure of a J domain in complex with a regulatory protein
      provides new insights into the function of the mitochondrial TIM23 translocase
      and the Hsp70 chaperone system in general.

PMID- 16977311
TI  - Opposing roles for Set2 and yFACT in regulating TBP binding at promoters.
AB  - Previous work links histone methylation by Set2 with transcriptional elongation.
      yFACT (Spt16-Pob3 and Nhp6) reorganizes nucleosomes and functions in both
      transcriptional initiation and elongation. We show that growth defects caused by
      spt16 or pob3 mutations can be suppressed by deleting SET2, suggesting that Set2
      and yFACT have opposing roles. Set2 methylates K36 of histone H3, and K36
      substitutions also suppress yFACT mutations. In contrast, set1 enhances yFACT
      mutations. Methylation at H3 K4 by Set1 is required for set2 to suppress yFACT
      defects. We did not detect an elongation defect at an 8 kb ORF in yFACT mutants.
      Instead, pob3 mutants displayed reduced binding of both pol II and TBP to the
      GAL1 promoter. Importantly, both GAL1 transcription and promoter binding of pol
      II and TBP are significantly restored in the pob3 set2 double mutant. Defects
      caused by an spt16 mutation are enhanced by either TBP or TFIIA mutants. These
      synthetic defects are suppressed by set2, demonstrating that yFACT and Set2
      oppose one another during transcriptional initiation at a step involving DNA
      binding by TBP and TFIIA.

PMID- 16977312
TI  - Substrate-mediated remodeling of methionine transport by multiple ubiquitin
      dependent mechanisms in yeast cells.
AB  - Plasma membrane transport of single amino-acid methionine in yeast is shown to be
      mediated by at least seven different permeases whose activities are
      transcriptionaly and post-transcriptionaly regulated by different ubiquitin
      dependent mechanisms. Upon high extracellular methionine exposure, three
      methionine-permease genes are repressed while four others are induced.
      SCF(Met30), SCF(Grr1) and Rsp5 ubiquitin ligases are the key actors of the
      ubiquitin-dependent remodeling of methionine transport. In addition to regulating
      the activity of Met4, the SCF(Met30) ubiquitin ligase is shown to convey an
      intracellular signal to a membrane initiated signaling pathway by controlling the
      nuclear concentration of the Stp1 transcription factor. By coupling intra- and
      extracellular metabolite sensing, SCF(Met30) thus allows yeast cells to
      accurately adjust the intermediary sulfur metabolism to the growth conditions.
      The multiple ubiquitin-dependent mechanisms that function in methionine transport
      regulation further exemplify the pervasive role of ubiquitin in the adaptation of
      single-cell organisms to environmental modifications.

PMID- 16977313
TI  - Sm core variation in spliceosomal small nuclear ribonucleoproteins from
      Trypanosoma brucei.
AB  - Messenger RNA processing in trypanosomes by cis and trans splicing requires
      spliceosomal small nuclear ribonucleoproteins (snRNPs) U1, U2, U4/U6, and U5, as
      well as the spliced leader (SL) RNP. As in other eukaryotes, these RNPs share a
      core structure of seven Sm polypeptides. Here, we report that the identity of the
      Sm protein constituents varies between spliceosomal snRNPs: specifically, two of
      the canonical Sm proteins, SmB and SmD3, are replaced in the U2 snRNP by two
      novel, U2 snRNP-specific Sm proteins, Sm15K and Sm16.5K. We present a model for
      the variant Sm core in the U2 snRNP, based on tandem affinity purification
      tagging and in vitro protein-protein interaction assays. Using in vitro
      reconstitutions with canonical and U2-specific Sm cores, we show that the
      exchange of two Sm subunits determines discrimination between individual Sm
      sites. In sum, we have demonstrated that the heteroheptameric Sm core structure
      varies between spliceosomal snRNPs, and that modulation of the Sm core
      composition mediates the recognition of small nuclear RNA-specific Sm sites.

PMID- 16977314
TI  - A streptococcal protease that degrades CXC chemokines and impairs bacterial
      clearance from infected tissues.
AB  - Group A Streptococcus (GAS) causes the life-threatening infection in humans known
      as necrotizing fasciitis (NF). Infected subcutaneous tissues from an NF patient
      and mice challenged with the same GAS strain possessed high bacterial loads but a
      striking paucity of infiltrating polymorphonuclear leukocytes (PMNs). Impaired
      PMN recruitment was attributed to degradation of the chemokine IL-8 by a GAS
      serine peptidase. Here, we use bioinformatics approach coupled with target
      mutagenesis to identify this peptidase as ScpC. We show that SilCR pheromone
      downregulates scpC transcription via the two-component system-SilA/B. In
      addition, we demonstrate that in vitro, ScpC degrades the CXC chemokines: IL-8
      (human), KC, and MIP-2 (both murine). Furthermore, using a murine model of human
      NF, we demonstrate that ScpC, but not the C5a peptidase ScpA, is an essential
      virulence factor. An ScpC-deficient mutant is innocuous for untreated mice but
      lethal for PMN-depleted mice. ScpC degrades KC and MIP-2 locally in the infected
      skin tissues, inhibiting PMN recruitment. In conclusion, ScpC represents a novel
      GAS virulence factor functioning to directly inactivate a key element of the host
      innate immune response.

PMID- 16977315
TI  - Fast-scanning atomic force microscopy reveals the ATP/ADP-dependent
      conformational changes of GroEL.
AB  - In order to fold non-native proteins, chaperonin GroEL undergoes numerous
      conformational changes and GroES binding in the ATP-dependent reaction cycle. We
      constructed the real-time three-dimensional-observation system at high resolution
      using a newly developed fast-scanning atomic force microscope. Using this system,
      we visualized the GroES binding to and dissociation from individual GroEL with a
      lifetime of 6 s (k=0.17 s(-1)). We also caught ATP/ADP-induced open-closed
      conformational changes of individual GroEL in the absence of qGroES and substrate
      proteins. Namely, the ATP/ADP-bound GroEL can change its conformation 'from
      closed to open' without additional ATP hydrolysis. Furthermore, the lifetime of
      open conformation in the presence of ADP ( approximately 1.0 s) was apparently
      lower than those of ATP and ATP-analogs (2-3 s), meaning that ADP-bound open-form
      is structurally less stable than ATP-bound open-form. These results indicate that
      GroEL has at least two distinct open-conformations in the presence of nucleotide;
      ATP-bound prehydrolysis open-form and ADP-bound open-form, and the ATP hydrolysis
      in open-form destabilizes its open-conformation and induces the 'from open to
      closed' conformational change of GroEL.

PMID- 16977316
TI  - Viewing single lambda site-specific recombination events from start to finish.
AB  - The site-specific recombination pathway by which the bacteriophage lambda
      chromosome is excised from its Escherichia coli host chromosome is a tightly
      regulated, highly directional, multistep reaction that is executed by a series of
      multiprotein complexes. Until now, it has been difficult to study the individual
      steps of such reactions in the context of the entire pathway. Using single
      molecule light microscopy, we have examined this process from start to finish.
      Stable bent-DNA complexes containing integrase and the accessory proteins IHF
      (integration host factor) and Xis form rapidly on attL and attR recombination
      partners, and synapsis of partner complexes follows rapidly after their
      formation. Integrase-mediated DNA cleavage before or immediately after synapsis
      is required to stabilize the synaptic assemblies. Those complexes that synapsed
      (approximately 50% of the total) yield recombinant product with a remarkable
      approximately 100% efficiency. The rate-limiting step of excision occurs after
      synapsis, but closely precedes or is concomitant with the appearance of a stable
      Holliday junction. Our kinetic analysis shows that directionality of this
      recombination reaction is conferred by the irreversibility of multiple reaction
      steps.

PMID- 16977317
TI  - A CapG gain-of-function mutant reveals critical structural and functional
      determinants for actin filament severing.
AB  - CapG is the only member of the gelsolin family unable to sever actin filaments.
      Changing amino acids 84-91 (severing domain) and 124-137 (WH2-containing segment)
      simultaneously to the sequences of gelsolin results in a mutant, CapG-sev,
      capable of severing actin filaments. The gain of severing function does not alter
      actin filament capping, but is accompanied by a higher affinity for monomeric
      actin, and the capacity to bind and sequester two actin monomers. Analysis of
      CapG-sev crystal structure suggests a more loosely folded inactive conformation
      than gelsolin, with a shorter S1-S2 latch. Calcium binding to S1 opens this latch
      and S1 becomes separated from a closely interfaced S2-S3 complex by an extended
      arm consisting of amino acids 118-137. Modeling with F-actin predicts that the
      length of this WH2-containing arm is critical for severing function, and the
      addition of a single amino acid (alanine or histidine) eliminates CapG-sev
      severing activity, confirming this prediction. We conclude that efficient
      severing utilizes two actin monomer-binding sites, and that the length of the WH2
      containing segment is a critical functional determinant for severing.

PMID- 16977318
TI  - Metabolic regulation of sodium-calcium exchange by intracellular acyl CoAs.
AB  - The sodium-calcium exchanger (NCX) is a critical mediator of calcium homeostasis.
      In the heart, NCX1 predominantly operates in forward mode to extrude Ca(2+);
      however, reverse-mode NCX1 activity during ischemia/reperfusion (IR) contributes
      to Ca(2+) loading and electrical and contractile dysfunction. IR injury has also
      been associated with altered fat metabolism and accumulation of long-chain acyl
      CoA esters. Here, we show that acyl CoAs are novel, endogenous activators of
      reverse-mode NCX1 activity, exhibiting chain length and saturation dependence,
      with longer chain saturated acyl moieties being the most effective NCX1
      activators. These results implicate dietary fat composition as a plausible
      determinant of IR injury. We further show that acyl CoAs may interact directly
      with the XIP (exchanger inhibitory peptide) sequence, a known region of anionic
      lipid modulation, to dynamically regulate NCX1 activity and Ca(2+) homeostasis.
      Additionally, our findings have broad implications for the coupling of Ca(2+)
      homeostasis to fat metabolism in a variety of tissues.

PMID- 16977319
TI  - Ptc1p regulates cortical ER inheritance via Slt2p.
AB  - Studies in the yeast Saccharomyces cerevisiae have shown that the inheritance of
      endoplasmic reticulum (ER), mitochondria, and vacuoles involves the capture of a
      tubular structure at the bud tip. Ptc1p, a serine/threonine phosphatase, has
      previously been shown to regulate mitochondrial inheritance by an unknown
      mechanism. Ptc1p regulates the high osmolarity glycerol mitogen-activated protein
      kinase (MAPK) pathway and has also been implicated in the cell wall integrity
      (CWI) MAPK pathway. Here we show that the loss of Ptc1p or the Ptc1p binding
      protein, Nbp2p, causes a prominent delay in the delivery of ER tubules to the
      periphery of daughter cells and results in a dramatic increase in the level of
      phosphorylated Slt2p, the MAPK in the CWI pathway. Either loss of Slt2p or
      inhibition of the CWI pathway by addition of sorbitol, suppresses the ER
      inheritance defect in the ptc1Delta and nbp2Delta mutants. Our findings indicate
      that Ptc1p and Nbp2p regulate ER inheritance through the CWI MAPK pathway by
      modulating the MAPK, Slt2p.

PMID- 16977320
TI  - A change in conformational dynamics underlies the activation of Eph receptor
      tyrosine kinases.
AB  - Eph receptor tyrosine kinases (RTKs) mediate numerous developmental processes.
      Their activity is regulated by auto-phosphorylation on two tyrosines within the
      juxtamembrane segment (JMS) immediately N-terminal to the kinase domain (KD).
      Here, we probe the molecular details of Eph kinase activation through mutational
      analysis, X-ray crystallography and NMR spectroscopy on auto-inhibited and active
      EphB2 and EphA4 fragments. We show that a Tyr750Ala gain-of-function mutation in
      the KD and JMS phosphorylation independently induce disorder of the JMS and its
      dissociation from the KD. Our X-ray analyses demonstrate that this occurs without
      major conformational changes to the KD and with only partial ordering of the KD
      activation segment. However, conformational exchange for helix alphaC in the N
      terminal KD lobe and for the activation segment, coupled with increased inter
      lobe dynamics, is observed upon kinase activation in our NMR analyses. Overall,
      our results suggest that a change in inter-lobe dynamics and the sampling of
      catalytically competent conformations for helix alphaC and the activation segment
      rather than a transition to a static active conformation underlies Eph RTK
      activation.

PMID- 16977321
TI  - p97 functions as an auxiliary factor to facilitate TM domain extraction during
      CFTR ER-associated degradation.
AB  - The AAA-ATPase (ATPase associated with various cellular activities) p97 has been
      implicated in the degradation of misfolded and unassembled proteins in the
      endoplasmic reticulum (ERAD). To better understand its role in this process, we
      used a reconstituted cell-free system to define the precise contribution of p97
      in degrading immature forms of the polytopic, multi-domain protein CFTR (cystic
      fibrosis transmembrane conductance regulator). Although p97 augmented both the
      rate and the extent of CFTR degradation, it was not obligatorily required for
      ERAD. Only a 50% decrease in degradation was observed in the complete absence of
      p97. Moreover, p97 specifically stimulated the degradation of CFTR transmembrane
      (TM) domains but had no effect on isolated cytosolic domains. Consistent with
      this, p97-mediated extraction of intact TM domains was independent of proteolytic
      cleavage and influenced by TM segment hydrophobicity, indicating that the
      relative contribution of p97 is partially determined by substrate stability.
      Thus, we propose that p97 functions in ERAD as a nonessential but important
      ancillary component to the proteasome where it facilitates substrate presentation
      and increases the degradation rate and efficiency of stable (TM) domains.

PMID- 16977323
TI  - The South African "bathing suit ichthyosis" is a form of lamellar ichthyosis
      caused by a homozygous missense mutation, p.R315L, in transglutaminase 1.

PMID- 16977322
TI  - Failure to prolyl hydroxylate hypoxia-inducible factor alpha phenocopies VHL
      inactivation in vivo.
AB  - Many functions have been assigned to the von Hippel-Lindau tumor suppressor gene
      product (pVHL), including targeting the alpha subunits of the heterodimeric
      transcription factor HIF (hypoxia-inducible factor) for destruction. The binding
      of pVHL to HIFalpha requires that HIFalpha be hydroxylated on one of two prolyl
      residues. We introduced HIF1alpha and HIF2alpha variants that cannot be
      hydroxylated on these sites into the ubiquitously expressed ROSA26 locus along
      with a Lox-stop-Lox cassette that renders their expression Cre-dependent.
      Expression of the HIF2alpha variant in the skin and liver induced changes that
      were highly similar to those seen when pVHL is lost in these organs. Dual
      expression of the HIF1alpha and HIF2alpha variants in liver, however, more
      closely phenocopied the changes seen after pVHL inactivation than did the
      HIF2alpha variant alone. Moreover, gene expression profiling confirmed that the
      genes regulated by HIF1alpha and HIF2alpha in the liver are overlapping but non
      identical. Therefore, the pathological changes caused by pVHL inactivation in
      skin and liver are due largely to dysregulation of HIF target genes.

PMID- 16977324
TI  - Deletion of prostaglandin E2 EP2 receptor protects against ultraviolet-induced
      carcinogenesis, but increases tumor aggressiveness.
AB  - Ultraviolet (UV) light is a complete carcinogen inducing and promoting squamous
      cell carcinoma (SCC) of the skin. Recent work has shown that SCC initiation and
      promotion are enhanced by prostaglandin E2 (PGE2). PGE2 interacts with specific
      EP receptors to regulate cellular functions. Previous work from our group has
      shown that the prostaglandin E2 EP2 receptor is a powerful regulator of
      keratinocyte growth. SKH-1 hairless mice lacking the EP2 receptor were therefore
      studied to understand how this growth signaling pathway contributes to
      photocarcinogenesis. Our data indicate that UV-irradiated mice lacking EP2
      receptors exhibit decreased proliferation and a poor capacity for epidermal
      hypertrophy in response to UV injury. In a chronic irradiation model, these
      animals were protected from tumor formation, developing 50% fewer tumors than
      wild-type controls. Despite this capacity to protect against tumorigenesis,
      animals lacking EP2 receptors grew tumors that were larger in size, with a more
      aggressive phenotype. Further study suggested that this susceptibility may be
      associated with synthesis of active metalloproteinase enzymes in greater
      quantities than keratinocytes expressing the EP2 receptor, thereby enhancing the
      invasive potential of EP2-/- cells.

PMID- 16977325
TI  - Integrin alpha2beta1 is required for regulation of murine wound angiogenesis but
      is dispensable for reepithelialization.
AB  - The alpha2beta1 integrin functions as the major receptor for collagen type I on a
      large number of different cell types, including keratinocytes, fibroblasts,
      endothelial cells, and a variety of inflammatory cells. Recently, we demonstrated
      that adhesion of keratinocytes to collagen critically depends on alpha2beta1,
      whereas fibroblasts can partly compensate for loss of alpha2beta1 in simple
      adhesion to collagen. However, in three-dimensional collagen matrices,
      alpha2beta1-null fibroblasts are hampered in generating mechanical forces. These
      data suggested a pivotal role for alpha2beta1 during wound healing in vivo.
      Unexpectedly, reepithelialization of excisional wounds of alpha2beta1-null mice
      was not impaired, indicating that keratinocytes do not require adhesion to or
      migration on collagen for wound closure. Whereas wound contraction and
      myofibroblast differentiation were similar, wound tensile strain was reduced in
      alpha2beta1-null mice, suggesting subtle changes in organization of the
      extracellular matrix. In addition, we observed reduced influx of mast cells into
      the granulation tissue, whereas infiltration of other inflammatory cells was not
      impaired. Interestingly, ablation of alpha2beta1 resulted in strong enhancement
      of neovascularization of granulation tissue and sponge implants. Both
      ultrastructurally and functionally, these new blood vessels appeared intact. In
      conclusion, our data show unique and overlapping functions of alpha2beta1
      integrin during murine cutaneous wound healing.

PMID- 16977326
TI  - Oxygen-dependent differentiation of human keratinocytes.
AB  - Oxygen is an essential micronutrient. Unlike many internal tissues, human
      epidermis obtains much of its oxygen supply from the atmosphere (21% oxygen), and
      it ordinarily experiences higher oxygen levels than internal tissues (estimated
      approximately 5%). To test whether epidermal cell growth and differentiation
      depend upon this higher oxygen level, keratinocyte cultures were studied at 21,
      5, and 2% oxygen concentrations. Compared to 21% oxygen, culture in 5% had little
      effect on growth but led to profound suppression of the differentiation program
      as assessed by expression of differentiation markers and formation of squames in
      the superficial layers. Culture in 2% oxygen reduced the growth rate as well as
      stratification and differentiation. In low-oxygen conditions, the cells exhibited
      increased colony-forming ability, consistent with a lower proportion of
      differentiated cells, and increased expression of vascular endothelial growth
      factor and cyclooxygenase-2. Growth in 21% oxygen led to higher levels of
      glutathione and expression of oxidant-responsive genes. Electrophoretic mobility
      supershift assay using an involucrin activator protein 1 (AP1) response element
      sequence revealed altered binding by proteins of the Jun and Fos families in
      nuclear extracts. The present data thus demonstrate oxygen-dependent
      differentiation in human keratinocytes, to which altered utilization of AP1
      transcriptional response elements may contribute.

PMID- 16977328
TI  - Membrane-localized activation of glucuronide prodrugs by beta-glucuronidase
      enzymes.
AB  - Gene-mediated enzyme prodrug therapy (GDEPT) seeks to increase the therapeutic
      index of anti-neoplastic agents by promoting selective activation of relatively
      nontoxic drug derivatives at sites of specific enzyme expression. Glucuronide
      prodrugs are attractive for GDEPT due to their low toxicity, bystander effect in
      the interstitial tumor space and the large range of possible glucuronide drug
      targets. In this study, we expressed human, murine and Esherichia coli beta
      glucuronidase on tumor cells and examined their in vitro and in vivo efficacy for
      the activation of glucuronide prodrugs of 9-aminocamptothecin and p-hydroxy
      aniline mustard. We show that (1) fusion of beta-glucuronidase to the Ig-like
      C(2)-type and Ig-hinge-like domains of the B7-1 antigen followed by the B7-1
      transmembrane domain anchored high levels of active murine and human beta
      glucuronidase on cells, (2) strong bystander killing of tumor cells was achieved
      in vitro by murine beta-glucuronidase activation of prodrug, (3) potent in vivo
      anti-tumor activity was achieved by prodrug treatment of tumors that expressed
      murine beta-glucuronidase and (4) the p-hydroxy aniline prodrug was more
      effective in vivo than the 9-aminocamptothecin prodrug. Our results demonstrate
      that surface expression of murine beta-glucuronidase for activation of a
      glucuronide prodrug of p-hydroxy aniline mustard may be useful for more selective
      therapy of cancer.

PMID- 16977329
TI  - Inflammatory caspases and inflammasomes: master switches of inflammation.
AB  - Fifteen years have passed since the cloning and characterization of the
      interleukin-1beta-converting enzyme (ICE/caspase-1), the first identified member
      of a family of proteases currently known as caspases. Caspase-1 is the
      prototypical member of a subclass of caspases involved in cytokine maturation
      termed inflammatory caspases that also include caspase-4 caspase -5, caspase -11
      and caspase -12. Efforts to elucidate the molecular mechanisms involved in the
      activation of these proteases have uncovered an important role for the NLR family
      members, NALPs, NAIP and IPAF. These proteins promote the assembly of
      multiprotein complexes termed inflammasomes, which are required for activation of
      inflammatory caspases. This article will review some evolutionary aspects,
      biochemical evidences and genetic studies, underlining the role of inflammasomes
      and inflammatory caspases in innate immunity against pathogens, autoinflammatory
      syndromes and in the biology of reproduction.

PMID- 16977330
TI  - Mitochondrial membrane depolarization in Drosophila apoptosis.

PMID- 16977331
TI  - Mitochondria frozen with trehalose retain a number of biological functions and
      preserve outer membrane integrity.
AB  - In apoptosis, Bcl-2-family proteins regulate the barrier function of the
      mitochondrial outer membrane (MOM), controlling the release of proapoptotic
      proteins from the intermembrane space into the cytoplasm. This process can be
      studied in vitro with freshly isolated mouse liver mitochondria. Unfortunately,
      mitochondria frozen/thawed in standard sucrose-mannitol buffers become leaky and
      useless for apoptosis research. However, here we show that mitochondria frozen in
      buffer containing the sugar, trehalose, maintained MOM integrity and
      responsiveness to Bcl-2-family proteins, much like fresh mitochondria. Trehalose
      also preserved ultrastructure, as well as biological functions such as ATP
      synthesis, calcium-induced swelling, transmembrane potential, and the import and
      processing of protein precursors. However, bioenergetic function was somewhat
      reduced. Thus, trehalose-frozen mitochondria retained most of the biological
      features of mitochondria including MOM integrity. Although not ideal for studies
      involving bioenergetics, this method will facilitate research on apoptosis and
      other mitochondrial functions that rely on an intact MOM.

PMID- 16977332
TI  - Apoptosome: a platform for the activation of initiator caspases.
AB  - Apoptosome refers to the adaptor protein complex that mediates the activation of
      an initiator caspase at the onset of apoptosis. In mammalian cells, caspase-9,
      caspase-8, and caspase-2 rely on the apoptotic protease-activating factor 1 (Apaf
      1)-apoptosome, death-inducing signaling complex (DISC), and PIDDosome,
      respectively, for activation. In Drosophila, activation of the caspase-9 homolog
      Dronc requires assembly of an apoptosome comprised of Dark/Hac-1/Dapaf-1. In
      Caenorhabditis elegans, activation of the caspase CED-3 is facilitated by the CED
      4-apoptosome. Recent biochemical and structural investigation revealed
      significant insights into the assembly and function of the various apoptosomes.
      Nonetheless, conclusive mechanisms by which the initiator caspases are activated
      by the apoptosomes remain elusive. Several models have been proposed to explain
      the activation process. The induced proximity model summarizes the general
      process of initiator caspase activation. The proximity-driven dimerization model
      describes how initiator caspases respond to induced proximity and offers an
      explanation for their activation. Regardless of how initiator caspases are
      activated, enhanced activity must be correlated with altered active site
      conformation. The induced conformation model posits that the activated
      conformation for the active site of a given initiator caspase is attained through
      direct interaction with the apoptosome or through homo-oligomerization
      facilitated by the apoptosome.

PMID- 16977333
TI  - The inflammatory caspases: guardians against infections and sepsis.
AB  - Innate immunity is the primary host defense against invading microorganisms.
      Pathogen recognition, mediated through an elaborate 'microbial sensing' system
      comprising the Toll-like and Nod-like receptor families results in the activation
      of caspase-1, which is a prerequisite for pathogen clearance. Tight regulation of
      caspase-1 is necessary to control the magnitude of the innate immune response and
      protect the organism from possible damaging effects such as sepsis. Recent
      findings from population studies and animal models of infectious diseases and
      sepsis have uncovered a role for full-length caspase-12 in blocking the
      inflammatory response initiated by caspase-1, thus predisposing the organism to
      severe sepsis and sepsis-related lethality. In this review, we re-examine the
      relationship among the Group I caspases, their known substrates and their
      proposed role in apoptosis. We further discuss their function in inflammation and
      bacterial clearance, with an emphasis on their regulatory mechanisms during the
      innate immune response.

PMID- 16977334
TI  - SERRATE: a new player on the plant microRNA scene.
AB  - MicroRNAs (miRNAs) function as sequence-specific guides that control gene
      expression by post-transcriptional gene silencing. Many miRNAs influence plant
      development by regulating the accumulation of transcripts that encode
      transcription factors. Mutants defective in miRNA accumulation, such as dcl1,
      hen1, hyl1 and ago1, have pleiotropic developmental phenotypes. The serrate-1 (se
      1) mutant of Arabidopsis also shows a highly pleiotropic phenotype, which
      overlaps with the phenotypes of mutants defective in miRNA accumulation. Although
      it has been proposed that SERRATE (SE) functions specifically in miRNA-mediated
      repression of the leaf polarity genes PHABULOSA and PHAVOLUTA, microarray
      analysis shows upregulation of many genes known to be the targets of miRNAs in se
      1. We show that SE is a general regulator of miRNA levels affecting the
      processing of primary miRNA to miRNA.

PMID- 16977335
TI  - A look at life from the homeodomain. Workshop on homeodomain proteins,
      hematopoietic development and leukemias.

PMID- 16977336
TI  - Coexistence of two protein folding states in the crystal structure of ribosomal
      protein L20.
AB  - The recent finding of intrinsically unstructured proteins defies the classical
      structure-function paradigm. However, owing to their flexibility, intrinsically
      unstructured proteins generally escape detailed structural investigations.
      Consequently little is known about the extent of conformational disorder and its
      role in biological functions. Here, we present the X-ray structure of the unbound
      ribosomal protein L20, the long basic amino-terminal extension of which has been
      previously interpreted as fully disordered in the absence of RNA. This study
      provides the first detailed picture of two protein folding states trapped
      together in a crystal and indicates that unfolding occurs in discrete regions of
      the whole protein, corresponding mainly to RNA-binding residues. The
      electrostatic destabilization of the long alpha-helix and a structural
      communication between the two L20 domains are reminiscent of those observed in
      calmodulin. The detailed comparison of the two conformations observed in the
      crystal provides new insights into the role of unfolded extensions in ribosomal
      assembly.

PMID- 16977337
TI  - The world of a worm: a framework for Caenorhabditis evolution. Workshop on the
      study of evolutionary biology with Caenorhabditis elegans and closely related
      species.

PMID- 16977338
TI  - Cancer despite immunosurveillance: immunoselection and immunosubversion.
AB  - Numerous innate and adaptive immune effector cells and molecules participate in
      the recognition and destruction of cancer cells, a process that is known as
      cancer immunosurveillance. But cancer cells avoid such immunosurveillance through
      the outgrowth of poorly immunogenic tumour-cell variants (immunoselection) and
      through subversion of the immune system (immunosubversion). At the early stages
      of carcinogenesis, cell-intrinsic barriers to tumour development seem to be
      associated with stimulation of an active antitumour immune response, whereas
      overt tumour development seems to correlate with changes in the immunogenic
      properties of tumour cells. The permanent success of treatments for cancer might
      depend on using immunogenic chemotherapy to re-establish antitumour immune
      responses.

PMID- 16977339
TI  - Competence and competition: the challenge of becoming a long-lived plasma cell.
AB  - Plasma cells provide humoral immunity. They have traditionally been viewed mainly
      as short-lived end-stage products of B-cell differentiation that deserve little
      interest. This view is changing, however, because we now know that plasma cells
      can survive for long periods in the appropriate survival niches and that they are
      an independent cellular component of immunological memory. Studies of the biology
      of plasma cells reveal a mechanism of intriguing simplicity and elegance that
      focuses memory provided by plasma cells on recently encountered pathogens while
      minimizing the 'fading' of memory for pathogens encountered in the distant past.
      This mechanism is based on competition for survival niches between newly
      generated plasmablasts and older plasma cells.

PMID- 16977340
TI  - [Intravitreal bevacizumab for recurring choroidal neovascularisation].
AB  - We administered bevacizumab intravitreally to treat a recurrence of CNV after
      confocal laser coagulation and photodynamic therapy in a 32-year-old female
      patient with a single functional eye. Before and after treatment the vision in
      the affected eye was stable at 1.0. Before administration of the VEGF antibody
      leakage was distinctly seen on fluorescein angiography, which did not appear on
      examination after the treatment. Despite the entailed measure of risk we decided
      in favour of intravitreal application because it seemed promising in view of
      earlier positive clinical experience with it in exsudative AMD and macular oedema
      following central retinal vein occlusion. Intravitreal bevacizumab is an
      alternative that should also be considered for the treatment of idiopathic CNV.
      Careful clinical studies will follow.

PMID- 16977341
TI  - [Sudden unilateral vision loss].

PMID- 16977342
TI  - Computer simulation of polypeptides in a confinement.
AB  - A coarse-grained model of polypeptide chains confined in a slit formed by two
      parallel impenetrable surfaces was studied. The chains were flexible
      heteropolymers (polypeptides) built of two kinds of united atoms-hydrophobic and
      hydrophilic. The positions of the united atoms were restricted to the vertices of
      a [310] lattice. The force field consisted of a rigorous excluded volume, a long
      distance potential between a pair of amino-acid residues and a local preference
      for forming secondary structure (helices). The properties of the chains were
      studied at a wide range of temperatures from good to bad solvent conditions.
      Monte-Carlo simulations were carried out using the algorithm based on the chain's
      local changes of conformation and employing the Replica Exchange technique. The
      influence of the chain length, the distances between the confining surfaces, the
      temperature and the force field on the dimension and the structure of chains were
      studied. It was shown that the presence of the confinement chain complicates the
      process of the chain collapse to low-temperature structures. For some conditions,
      one can find a rapid decrease of chain size and a second transition indicated by
      the rapid decrease of the total energy of the system.

PMID- 16977343
TI  - Glutathione S-transferase M1 and GST T1 genetic polymorphisms and Raynaud's
      phenomenon in French vinyl chloride monomer-exposed workers.
AB  - Occupational vinyl chloride monomer (VCM) exposure can induce Raynaud's
      phenomenon (RP). However, not all VCM workers developed RP, which suggests an
      underlying genetic susceptibility. Genetic polymorphisms of glutathione S
      transferases (GSTs), involved in VCM metabolism, have been shown to influence
      certain VCM-related health effects. We have conducted a case-control study of 58
      subjects with RP along with 247 subjects without RP, from a population of 305
      French workers exposed or formerly exposed to VCM, to assess any association
      between GST M1 and GST T1 gene polymorphisms, either separately or in
      combination, and the presence of RP. None of the GST M1 or GST T1 genotypes were
      significantly associated with the presence of RP among studied VCM workers. A
      combination of positive genotypes for both GST M1 and GST T1 was significantly
      associated with RP presence, compared to the other combinations of genotypes
      (OR=2.1, 95% CI=1.1-3.8). OR adjusted for age, smoking status, alcohol
      consumption and history of treated hypertension did not reach significance
      (OR=2.0, 95% CI=0.9-5.2). None of the GST M1 and GST T1 genotypes seem to
      contribute separately to the presence of RP, suggesting that they are not, when
      taken alone, a major determinant of interindividual variability for VCM-induced
      PR. However, the combination of both positive GST M1 and GST T1 genotypes appears
      to contribute slightly to susceptibility to RP in VCM-exposed subjects.
      Nevertheless, our study-the first to examine the role of a genetic component in
      the occurrence of RP secondary to occupational exposure to a chemical
      corroborates the previous considerations that interaction between the genetic
      constitution and environmental factors is of importance in determining the health
      adverse effects of VCM exposure.

PMID- 16977345
TI  - Effects of different kinds of meshes on postoperative adhesion formation in the
      New Zealand White rabbit.
AB  - The aim of this study was to compare the effect of different kinds of surgical
      meshes on postoperative adhesion formation. Forty-two New Zealand White rabbits
      were studied. The rabbits were grouped into six groups, according to the type of
      surgical meshes (Prolene, Mersilene, Vypro, polytetraflouroethylene (PTFE),
      Proceed and control group) implanted into the peritoneum cavity. Thirty days
      after the operation, the relaparotomies were carried out, and any adhesions
      observed between the implanted mesh and tissues were evaluated and graded. The
      mean adhesion degree was 9.2 in the Mersilene mesh group, 9.5 in the Prolene mesh
      group, 9.7 and in the Vypro mesh group (P > 0.05). The mean adhesion degree was 1
      in the control group, 2.75 in the Proceed mesh group and 2.25 in the PTFE mesh
      group. There was a significant difference in adhesion degree between the control,
      Proceed and PTFE groups and the Prolene, Mersilene and Vypro mesh groups. The
      adhesion degree was significantly lower in the Proceed and PTFE mesh groups when
      comparing them with the Prolene, Mersilene and Vypro meshes.

PMID- 16977344
TI  - Collagenase and surgical disease.
AB  - Collagen types I, II, and III are the most abundant extracellular matrix (ECM)
      proteins. Collagenase is a member of the matrix metalloproteinase (MMP) family of
      enzymes, and is the principal enzyme involved with collagen degradation. Cellular
      ECM interactions are vitally important to tissue structure and function. In this
      review, we summarize recent work that highlights the role of collagenase in ECM
      remodeling and repair, and further report that alterations of collagenase
      expression, function, and/or regulation are found in many diverse disease states,
      including aortic aneurysms, tumor invasiveness and their metastases, and hernias.
      Collagenase is intimately involved in many surgical diseases, and represents a
      potential target for therapy.

PMID- 16977346
TI  - NOD2 allele variants in patients with rheumatoid arthritis.
AB  - Recent reports have proven the importance of genetic factors and inflammation in
      the pathogenesis of rheumatoid arthritis (RA). In the current study, the
      frequency of NOD2/CARD15 gene variants (R702W, G908R, and L1007fsinsC) was
      examined in a group of 243 RA patients and 220 healthy controls. There were no
      statistically significant differences in distribution of NOD2 variant alleles
      between RA patients and controls. Moreover, there was no significant association
      between NOD2 variant alleles and joint erosions, extraarticular manifestations,
      rheumatoid factor, number of swollen and tender joints, and erythrocyte
      sedimentation rate. The results of the present study suggest that NOD2 allele
      variants have no significant influence on RA susceptibility, activity, and
      severity.

PMID- 16977347
TI  - TRPC6 silencing in primary airway smooth muscle cells inhibits protein expression
      without affecting OAG-induced calcium entry.
AB  - TRPC proteins have been described as non-selective cation channels and are
      thought to be involved in the regulation of Ca(2+) movement in various cells,
      including airway smooth muscle (ASM) cells. In order to study the role of these
      channels in ASM cells, transfection of a small interfering RNA (siRNA) designed
      against the TRPC6 channel was performed in guinea pig primary ASM cells. This
      specific siRNA was complexed with the new X-TremeGene (X-TG) chemical
      transfection reagent, whose efficiency and low cytotoxicity were determined by
      the use of a non-silencing rhodamine-tagged siRNA. It was found that more than
      95% of cells were transfected by an optimized protocol. Verification of TRPC6
      transcript down-regulation was determined by RT-PCR while Western blot analysis
      attested to lower protein content in the microsomal fraction. Micro
      spectrofluorimetry measurements of control and siRNA-treated cells revealed that
      lower TRPC6 expression did not affect OAG-induced intracellular Ca(2+) movement.
      Thus, TRPC6 channels cannot be defined as simple Ca(2+) transporters but more
      likely as protein complexes supporting monovalent cation conductance in ASM
      cells. These conductances would in turn facilitate membrane depolarization of
      high input resistance cells, Ca(2+) channel activation and tone increase. In
      conclusion, this study defines a valuable model of RNA interference study in
      primary cultures of ASM cells, eventually allowing for silencing of other target
      proteins for which no pharmacological modulators are currently available.

PMID- 16977348
TI  - Strategic use of evidence during police interviews: when training to detect
      deception works.
AB  - Research on deception detection in legal contexts has neglected the question of
      how the use of evidence can affect deception detection accuracy. In this study,
      police trainees (N=82) either were or were not trained in strategically using the
      evidence when interviewing lying or truth telling mock suspects (N=82). The
      trainees' strategies as well as liars' and truth tellers' counter-strategies were
      analyzed. Trained interviewers applied different strategies than did untrained.
      As a consequence of this, liars interviewed by trained interviewers were more
      inconsistent with the evidence compared to liars interviewed by untrained
      interviewers. Trained interviewers created and utilized the statement-evidence
      consistency cue, and obtained a considerably higher deception detection accuracy
      rate (85.4%) than untrained interviewers (56.1%).

PMID- 16977355
TI  - Dermafascial fixation suture: a technique for a more durable projection with
      short-scar (vertical) reduction mammaplasty.
AB  - BACKGROUND: Short-scar reduction mammaplasty has several advantages over the
      traditional technique, mainly reduced scarring and superior long-term breast
      shape. Multiple modifications of the short scar reduction mammaplasty technique
      have been made in an effort to decrease the learning curve while improving the
      results. The authors present another modification of the short-scar technique for
      a more durable projection without reliance on a skin envelope. METHODS: The
      perimeters of the medial pedicle and the nipple-areola complex are marked, and
      the medial pedicle is deepithelialized. A 2 x 5-cm skin area at the inferior
      border of the pedicle is further deepithelialized, then pexied to the pectoralis
      fascia in a superomedial direction using a nonabsorbable monofilamanet suture
      with a horizontal mattress suturing technique. RESULTS: Taking the suture bites
      from the dermis rather than the breast parenchyma for the pexy aims to spare the
      pedicle's circulation. This durable internal rearrangement of the breast
      parenchyma with dermafascial pexy further decreases the tension at the nipple
      areola complex because the final breast shape no longer relies on the skin
      closure. Suture spitting at the nipple-areola complex also is prevented with
      elimination of the purse-string suture because there is no need for a further
      decrease in the tension with the purse-string suture after the dermafascial pexy.
      CONCLUSIONS: The authors believe that the dermafascial pexy is a concept more
      than a technique. It incorporates the two strongest structures, the dermis and
      the fascia, to achieve more durable results not only with reduction mammaplasty,
      but also with any aesthetic breast surgery that uses the pedicles.

PMID- 16977356
TI  - International Breast Implant Registry: a user report.
AB  - The International Breast Implant Registry (IBIR) was founded in 2002 under the
      auspices of the International Plastic, Reconstructive, and Aesthetic Surgery
      Foundation (IPRAF), the International Confederation for Plastic, Reconstructive,
      and Aesthetic Surgery (IPRAS), and the European and International Committee for
      Quality Assurance, Medical Technologies, and Devices in Plastic (EQUAM) on the
      basis of continuous discussion about the safety and compatibility of different
      breast implants. The IBIR aims to integrate and replace the already existing
      national breast implant registries. It also is assumed that the European
      Parliament, the Food and Drug Administration, and international organizations of
      plastic and aesthetic surgeons will postulate obligatory international breast
      implant registration. Currently, IBIR is in a pilot phase with the goal of
      understanding data collection issues and concerns in various countries whereby
      the data entered to date will be completely available in the final version. A
      well-established global registry represents an important tool of quality
      assurance. By publishing their experiences in applying the registry, the authors
      aim to encourage more plastic and aesthetic surgeons to submit their cases to the
      registry and thus enhance its value as a successful and powerful device.

PMID- 16977357
TI  - Current methods for brow fixation: are they safe?
AB  - BACKGROUND: No single technique for fixation of the scalp after forehead-lift is
      universally accepted. Complications such as alopecia, loss of elevation, implant
      palpability, paresthesia, and dural injury are possible with the variety of
      techniques used currently. This anatomic study was designed to evaluate the
      thickness of the calvarium at selected points used in brow fixation. The depth of
      cranial penetration necessary for currently used techniques is measured and
      compared. METHODS: In a study of 14 fresh adult cadavers, calvarial thickness was
      measured at selected points (A-F) used in various brow-lifting procedures. This
      was accomplished by drilling holes in selected points and using a depth gauge to
      measure thickness. Immediately adjacent to selected points, the cranium is
      prepared for brow fixation using the following techniques: cortical tunnels, 2.0
      mm screw fixation (10, 12, and 14 mm), the Mitek 2.0-mm Quickanchor screw, and
      the Endotine 3.5 Forehead Device. The depths required for adequate fixation and
      the potential for cranial penetration through the inner table with all the
      standard techniques are compared. RESULTS: Depth analysis by mean values showed
      that sites posterior to the coronal suture (points C-F) were thickest. Depth
      analysis of sites stratified by gender showed that mean values for the thickness
      of female skulls were greater than those for males. A review of fixation methods
      found that cortical tunnels at 45 degrees angles never penetrated the inner table
      in any of the 14 skulls. Mitek screws never penetrated the inner table, and one
      Endotine post penetrated the inner table on the left side of one cadaver skull.
      After placement of 10-, 12-, and 14-mm miniscrews at each of the sites, it was
      found that three penetrated the inner table. The penetrations all were at far
      lateral sites, posterior to the coronal suture. CONCLUSION: Variation in skull
      thickness exists among cadaver specimens at different sites on the skull. In this
      study, thickness increased medially and posteriorly. Women tended to have thicker
      skulls than men, and age was not a major variable. This is consistent with
      findings in previous work. Given the unpublished reports of inner table
      penetration, with cerebrospinal fluid leak after invasive brow fixation, it
      behooves the surgeon to keep in mind the anatomy of the calvarium and its
      nuances.

PMID- 16977358
TI  - Safe total corporal contouring with large-volume liposuction for the obese
      patient.
AB  - The advent of the tumescent technique in 1987 allowed for safe total corporal
      contouring as an ambulatory, single-session megaliposuction with the patient
      under regional anesthesia supplemented by local anesthetic only in selected
      areas. Safety and aesthetic issues define large-volume liposuction as having a
      5,000-ml aspirate, mega-volume liposuction as having an 8,000-ml aspirate, and
      giganto-volume liposuction as having an aspirate of 12,000 ml or more.
      Clinically, a total volume comprising 5,000 ml of fat and wetting solution
      aspirated during the procedure qualifies for megaliposuction/large-volume
      liposuction. Between September 2000 and August 2005, 470 cases of liposuction
      were managed. In 296 (63%) of the 470 cases, the total volume of aspirate
      exceeded 5 l (range, 5,000-22,000 ml). Concurrent limited or total-block
      lipectomy was performed in 70 of 296 cases (23.6%). Regional anesthesia with
      conscious sedation was preferred, except where liposuction targeted areas above
      the subcostal region (the upper trunk, lateral chest, gynecomastia, breast, arms,
      and face), or when the patient so desired. Tumescent infiltration was achieved
      with hypotonic lactated Ringer's solution, adrenalin, triamcinalone, and hyalase
      in all cases during the last one year of the series. This approach has clinically
      shown less tissue edema in the postoperative period than with conventional
      physiologic saline used in place of the Ringer's lactate solution. The amount
      injected varied from 1,000 to 8,000 ml depending on the size, site, and area.
      Local anesthetic was included only for the terminal portion of the tumescent
      mixture, wherever the subcostal regions were infiltrated. The aspirate was
      restricted to the unstained white/yellow fat, and the amount of fat aspirated did
      not have any bearing on the amount of solution infiltrated. There were no major
      complications, and no blood transfusions were administered. The hospital stay
      ranged from 8 to 24 h for both liposuction and liposuction with a lipectomy.
      Serous discharge from access sites and serosanguinous fluid accumulation
      requiring drainage were necessitated in 32 of 296 cases (10.8%). Minor
      recontouring touch-ups were requested in 17 of 296 cases (5.7%). Early ambulation
      was encouraged for mobilization of third-space fluid shifts to expedite recovery
      and to prevent deep vein thrombosis. Follow-up evaluation ranged from 6 to 52
      months, with 38 (12.8%) of 296 patients requesting further sessions for other new
      areas. Average weight reduction observed was 7 to 11.6 kg (approx. 4 to 10% of
      pre-operative body weight). Meticulous perioperative monitoring of systemic
      functions ensures safety in tumescent megaliposuction for the obese, and
      rewarding results are achieved in a single sitting.

PMID- 16977359
TI  - The effects of zafirlukast on capsular contracture: preliminary report.
AB  - Capsular contracture after breast augmentation is a distressing, troublesome
      event both for the patient and the surgeon. Fibrosis transforms the prosthesis
      into a hardened sphere, turning the initially satisfactory cosmetic result into a
      deformed mass. Treatment for capsular contracture can be either surgical,
      consisting of capsulotomy or capsulectomy with implant replacement, or
      pharmacologic, consisting of intracapsular instillation of steroids and
      antibiotics. The success rates for both types of treatment vary. Although
      capsular contracture is a multifactorial process, one common denominator in the
      successful treatment of this complication is believed to be the abatement of
      inflammation. Leukotriene antagonists have emerged recently as effective
      prophylactic agents for reactive airway diseases. Anecdotal reports have
      indicated that zafirlukast and montelukast effectively reverse capsular
      contracture. The authors investigated whether capsular contracture varies
      significantly over time after zafirlukast therapy by studying 20 women who had
      breast prostheses implanted and then experienced the development of capsular
      contracture. The results suggest that capsular contracture responds favorably to
      treatment with zafirlukast. The findings indicate that zafirlukast may reduce
      pain and breast capsule distortion for patients with long-standing contracture
      who either are not surgical candidates or do not wish to undergo surgery.

PMID- 16977360
TI  - A new method for umbilicus reconstruction: preliminary report.
AB  - The umbilicus is a very important component of the abdominal aesthetic view.
      However, loss of the umbilicus for any reason is a challenging problem. Various
      methods for umbilicus reconstruction have been published. Most of these methods
      are complex, and the surgical outcome is mostly unsatisfactory for the patients.
      The authors have developed a simple method for umbilicus reconstruction using a
      bilobed flap.

PMID- 16977361
TI  - Breast shaping by an isolated tissue flap.
AB  - Breast reshaping surgery for tuberous breast, breast reduction, and mastopexy
      procedures aim to keep the gained shape for a long time. In breast reduction, the
      surgeon must avoid loss of fullness in the upper pole, descent of the breast mass
      known as secondary dropout, and relapsed shape of the repaired tuberous breasts.
      As described in their clinical report, the authors use a caudally based thoracic
      wall flap to avoid these problems. The blood supply to the breast comes from two
      main sources: the mammary internal and lateral arteries. Because of vessels
      constantly perforating the pectoralis major muscle, it is possible to isolate a
      caudally based thoracic wall flap. These vessels originate from intercostal
      arteries as anteromedial intercostal perforators, and from the thoracoacromial
      artery as in the skin paddle of the pectoralis major muscle flap. This flap is
      long enough to reach every part of the breast where it is needed. Between January
      2002 and June 2005, 64 patients underwent procedures in which the caudally based
      thoracic wall flap was used.

PMID- 16977362
TI  - Use of aerosolized bovine-prepared fibrin glue for skin fixation after primary
      open rhinoplasty: a prospective randomized and controlled trial.
AB  - BACKGROUND: Fibrin glue has been used in diverse areas of plastic surgery. To the
      authors' knowledge, no clinical controlled trial studies have reported its use
      for open rhinoplasty. METHODS: A prospective, randomized, masked clinical trial
      was designed to demonstrate that aerosolized bovine-prepared fibrin glue used in
      open rhinoplasty controls skin fixation (flap movement), edema, hematomas,
      ecchymosis, bleeding, and cosmetic results 1 and 12 months postoperatively. The
      results were reviewed by two blinded plastic surgeons who assessed postoperative
      photographs using the Strasser score. Other items such as columella scar, pain,
      surgery/recovery time, and patient satisfaction also were evaluated. RESULTS: A
      computer system was used to randomize 22 consecutive open primary rhinoplasties.
      Cosmetic analysis did not differ significantly between the group redraped with
      fibrin glue and the control group. Patient satisfaction was the only outcome that
      significantly favored the active group. None of the other items or adverse events
      significantly differed between the two groups, including operative time and pain.
      CONCLUSIONS: Fibrin glue is believed to reduce bleeding and to improve the
      adherence of tissues. The only statistical difference in this study favored the
      patient satisfaction cosmetic score of the group that received fibrin glue.

PMID- 16977363
TI  - Subfascial transaxillary breast augmentation without endoscopic assistance:
      technical aspects and outcome.
AB  - BACKGROUND: Although transaxillary breast augmentation (TBA) is a well-studied
      procedure, few previous reports exist concerning the subfascial technique,
      especially without endoscopic assistance. This study aimed to analyze the
      feasibility of the technique after breast augmentation in terms of its
      indication, surgical technique, limitations, and clinical outcome. METHODS: For
      this study, 42 patients underwent TBA without endoscopic assistance. The
      technique was indicated for patients with breasts of small or moderate volume
      without ptosis, patients who wanted no breast scars, and patients who had a
      poorly defined inframammary fold. The mean follow-up period was 16 months.
      Implant and incision approach complications were evaluated. Information on
      patient satisfaction was collected. RESULTS: A total of 14 complications occurred
      in 42 patients, all of them minor. Axillary incision-related complications
      occurred in 26% of the patients, as represented by a late axillary subcutaneous
      band (119%), sensory loss in the inner aspect of the arm (71%), and a
      hypertrophic scar and small wound dehiscence (71%). No patient presented with
      capsular contracture, visible rippling, or infection. Most of the patients (93%)
      were either very satisfied or satisfied with their result, and none regretted the
      surgery. CONCLUSION: The TBA procedure without endoscopic assistance is a simple
      and reliable technique for breast augmentation. Most of the complications in this
      study were minor and predictable. They did not interfere with the aesthetic
      outcome nor the normal postoperative recovery. With TBA, success depends on
      patient selection as well as careful intra- and postoperative management.

PMID- 16977364
TI  - A simple way to drain hematoma of the scalp.

PMID- 16977365
TI  - Modified lateral thoracodorsal flap: a way out of a difficult problem.

PMID- 16977366
TI  - Umbilical reconstruction for patients with a midline scar.
AB  - The authors describe an approach to neo-umbilicoplasty for patients with vertical
      midline scars and those who have undergone extensive tegumental resections after
      bariatric surgery. Two lateral pedicle flaps sutured to each other are used to
      shape a cutaneous wall tube in which the inverted end is anchored to the
      aponeurotic plane. A navel cavity of adequate scoop is shaped with no surrounding
      scar, in addition to relief of the strain along the vertical scar, which will be
      less prone to hypertrophy and will have a better cosmetic appearance. This
      article presents seven cases of umbilical reconstruction using this technique.

PMID- 16977368
TI  - The application of mesh support in periareolar breast surgery: clinical and
      mammographic evaluation.

PMID- 16977369
TI  - Comparison between intramuscular and perimuscular injections of botulinum toxin
      type A.
AB  - BACKGROUND: Botulinum toxin type A (BTX-A) must be injected in the intramuscular
      area to exert its paralytic effect. The durability of the BTX-A effect varies in
      different patients, and this fact can result from different locations of the drug
      injection, for example, the muscle peripheral area (perimuscular). This study
      aimed to evaluate whether a difference exists in the effect duration of the
      muscle paralysis between intramuscular and perimuscular injections of BTX-A.
      METHODS: This study used 18 male New Zealand rabbits divided into two groups (A
      and B) based on the location of the BTX-A injection. The group A animals received
      10 units of BTX-A diluted with 0.1 ml of normal saline injected perimuscularly.
      The group B animals received the same dosage injected in the intramuscular area
      of the left masseter muscle. An electroneurophysiologic study was performed 1
      week before the experiment for all the animals, then repeated 1, 4, and 8 weeks
      after the toxin injection. RESULTS: The amplitude values recorded in the masseter
      muscle were significantly lower in both groups throughout the study than the
      physiologic amplitude. The comparison between groups A and B did not show any
      statistically significant amplitude variations throughout the 8 weeks.
      CONCLUSION: No significant difference in the neuromuscular blockade induced by
      botulinum toxin type A was observed between injections into the muscle peripheral
      area and intramuscular injections.

PMID- 16977370
TI  - Another use of the alar cartilaginous flap.
AB  - BACKGROUND: Resection of the cephalic or middle portion of lateral crura of alar
      cartilages is a method for correcting bulbous nose in which the resected
      cartilages usually are discarded, resulting in a waste of autologous tissues. A
      silastic implant usually is used to correct saddle nose in Asian countries, but
      implant extrusion, a severe complication, sometimes occurs. Cartilage flaps were
      first reported by Jose to increase the projection of the nasal tip. In this
      study, the authors used cartilaginous flaps of the lateral crura to wrap the tip
      of the nasal implant for patients with bulbous and saddle noses. This study aimed
      to investigate the application of cartilaginous flaps of lateral crura. METHODS:
      A flap was created from the cephalic portion of the lateral crus of the alar
      cartilage, leaving the caudal portion intact. The cartilage flap remained
      attached at the level of the original domal segment of the middle crura. It was
      rotated over to wrap the tip of the silastic implant, then sutured to the other
      side flap. RESULTS: From March 2003, 19 patients were treated with this
      technique. The results were satisfactory without implant extrusion or any other
      complications except for nonobvious scars. CONCLUSION: The cartilage flap can
      reduce the incidence of implant extrusion and help to reduce the size of the
      bulbous tip.

PMID- 16977371
TI  - A stratigraphic approach to the superficial musculoaponeurotic system and its
      anatomic correlation with the superficial fascia.
AB  - The superficial musculoaponeurotic system (SMAS) is not included in the
      International Anatomic Terminology, although it is a fundamental anatomical
      structure in plastic surgeons. In the literature, the concept of the SMAS is not
      clear, leading to repercussions in the treatment of the SMAS via the various
      techniques for rhytidoplasty. This review article, in its aim to conceptualize
      the SMAS, has as a referential parameter the basic stratigraphic pattern of the
      human body construction. A systematic review of the literature was performed
      through Medline, ISI-Web of Science, and Lilacs databases as well as through
      classical treatises of anatomy for analyses of the stratigraphic principle of
      SMAS and its relationship to the fascia. In fact, SMAS, an anatomic entity, is
      part of this construction model. The stratigraphic approach followed in this
      article to describe the SMAS is novel in the literature and allows for a unified
      anatomic understanding of SMAS for the scientific community.

PMID- 16977372
TI  - Late intracapsular seroma in subfascial buttock augmentation: a case report.
AB  - Late intracapsular seroma and hematoma have been described frequently as a
      complication of breast augmentation surgery. However, there are few reports of
      late intracapsular seroma in buttock augmentation. Textured and polyurethane
      implants have been used for subfascial enlargement of the buttocks. In this
      article, the authors report a large late intracapsular bilateral seroma caused by
      a retrofascial polyurethane-covered implant used for buttock augmentation: 1,200
      ml on one side and 300 ml on the other. This patient's intracapsular seroma was
      of sudden onset 2 years and 6 months after surgery, and apparently had no
      relation to any trauma, use of medication, or physical exercise. Local tissues,
      including the gluteal fascia, were distended such that the implant was replaced
      inside the muscle and there was no relapse of the seroma. Late intracapsular
      hematomas or seromas from implants for buttock and breast augmentation may have
      the same etiology, and textured implants seem to be involved. All the reports on
      the matter are associated with textured implants. Any late seroma or hematoma
      caused by a smooth implant is related to an additional factor that may be
      considered as the etiologic agent. Further studies aimed at a large-scale
      assessment of the cause and actual incidence of late seromas and hematomas from
      textured implants are required.

PMID- 16977373
TI  - Abdominoplasty complications: a comprehensive approach for the treatment of
      chronic seroma with pseudobursa.
AB  - Abdominoplasty is an extensive surgical operation, often followed by a
      significant number of local and general complications. Some studies indicate that
      the risk of severe complications, including mortality, ranges from 1 in 617 to 1
      in 2,320 cases. Seroma is one of the serious consequences that follows each type
      of abdominal contour surgery, from suction-assisted lipoplasty to standard and
      limited abdominoplasty. A case of a 46-year-old women who underwent standard
      abdominoplasty and liposuction during the same procedure is presented. In the
      follow-up examination, a chronic seroma with pseudobursa was observed. The
      pseudobursa was evacuated multiple times under ultrasound control. During one
      evacuation, 2,010 ml of seroma was evacuated. Because of the prolonged Seroma
      formation, the pseudobursa grew, creating a tumor-like effect in the front
      abdominal wall. In a second operation (miniabdominoplasty), the pseudobursa was
      completely excised, and the material was sent for analysis. Progressive tension
      sutures were placed in additional lines to decrease the dead space, and to
      decrease movement between the abdominal flap and the musculoaponeurotic layer, as
      suggested by Saltz and Matarasso. Suction drainage with a compressive girdle was
      maintained for 2 weeks after the second operation. The follow-up assessment,
      performed 3 months after the second operation, showed no infection, skin
      necrosis, hernia formation, or new chronic seroma with pseudobursa.

PMID- 16977374
TI  - Prevalence of perianal intraepithelial neoplasia in HIV-infected patients
      referred for high-resolution anoscopy.
AB  - PURPOSE: This study was designed to describe perianal disease in a cohort of HIV
      infected patients referred for high-resolution anoscopy. METHODS: A retrospective
      chart review was performed on 52 HIV-infected patients referred for high
      resolution anoscopy from 2001 to 2005. All patients underwent anal canal and
      perianal high-resolution anoscopy in the office with biopsy of suspicious areas.
      Patients with high-grade intraepithelial perianal lesions underwent multiple
      biopsies under general anesthesia in the operating room to rule out malignancy.
      RESULTS: Of the 52 patients, 19 (37 percent) had perianal abnormalities noted on
      high-resolution anoscopy and underwent punch biopsy. The mean duration of known
      HIV infection in these 19 patients (15 males) was 10.6 years, with 17 on highly
      active antiretroviral therapy for the last 3-month period. Mean CD4 count was 371
      cells/microl. Office perianal biopsies diagnosed two patients with invasive
      squamous-cell carcinoma and nine with high-grade squamous intraepithelial lesion.
      Seven of the nine patients with perianal high-grade squamous intraepithelial
      lesion on office biopsy were submitted to multiple biopsies under general
      anesthesia. One of these seven had an occult perianal squamous-cell carcinoma.
      CONCLUSIONS: Perianal disease was common in this group of HIV-infected patients;
      11 patients (21 percent of total) were diagnosed with squamous-cell carcinoma or
      high-grade squamous intraepithelial lesion. Because only 19 patients had
      clinically suspicious perianal lesions biopsied, this may be an underestimate.
      Our data suggest that anal canal neoplasia often is accompanied by perianal
      disease and illustrates the need for biopsy of any suspicious perianal lesions.

PMID- 16977376
TI  - Current concepts in apoptosis: the physiological suicide program revisited.
AB  - Apoptosis, or programmed cell death (PCD), involves a complex network of
      biochemical pathways that normally ensure a homeostatic balance between cellular
      proliferation and turnover in nearly all tissues. Apoptosis is essential for the
      body, as its deregulation can lead to several diseases. It plays a major role in
      a variety of physiological events, including embryonic development, tissue
      renewal, hormone-induced tissue atrophy, removal of inflammatory cells, and the
      evolution of granulation tissue into scar tissue. It also has an essential role
      in wound repair. The various cellular and biochemical mechanisms involved in
      apoptosis are not fully understood. However, there are two major pathways, the
      extrinsic pathway (receptor-mediated apoptotic pathway) and the intrinsic pathway
      (mitochondria-mediated apoptotic pathway), which are both well established. The
      key component in both is the activation of the caspase cascade. Caspases belong
      to the family of proteases that ultimately, by cleaving a set of proteins, cause
      disassembly of the cell. Although the caspase-mediated proteolytic cascade
      represents a central point in the apoptotic response, its initiation is tightly
      regulated by a variety of other factors. Among them, Bcl-2 family proteins, TNF
      and p53 play pivotal roles in the regulation of caspase activation and in the
      regulation of apoptosis. This review summarizes the established concepts in
      apoptosis as a physiological cell suicide program, highlighting the recent and
      significant advances in its study.

PMID- 16977375
TI  - Prevalence of anti-locus coeruleus immunoreactivity in CSF of patients with
      autonomic failure.
AB  - In this study we evaluated by indirect immunohistochemistry the prevalence of
      cerebrospinal fluid (CSF) antibodies reacting with structures of rat pons/medulla
      in patients with multiple system atrophy (MSA) (n = 29), Parkinson disease with
      neurogenic orthostatic hypotension (n = 13), or pure autonomic failure (n = 11)
      and in control subjects without autonomic failure (n = 33). About 10-20% of CSF
      samples had positive immunoreactivity to rat locus coeruleus (LC), regardless of
      clinical diagnosis. The results failed to confirm the previously reported high
      prevalence of immune binding to rat LC in CSF from patients with MSA.

PMID- 16977377
TI  - Endoplasmic reticulum stress and apoptosis.
AB  - Cell death is an essential event in normal life and development, as well as in
      the pathophysiological processes that lead to disease. It has become clear that
      each of the main cellular organelles can participate in cell death signalling
      pathways, and recent advances have highlighted the importance of the endoplasmic
      reticulum (ER) in cell death processes. In cells, the ER functions as the
      organelle where proteins mature, and as such, is very responsive to extracellular
      intracellular changes of environment. This short overview focuses on the known
      pathways of programmed cell death triggering from or involving the ER.

PMID- 16977378
TI  - Abnormal histone acetylase and deacetylase expression and function in lung
      inflammation.
AB  - Post-translational modifications in DNA and histone proteins are heritable
      changes that are not coded for in the DNA sequence itself but play an important
      role in the control of gene expression. These modifications include histone
      acetylation, methylation, ubiquitination, sumoylation and phosphorylation. These
      changes are not only critical for generating diversity of cell types during
      mammalian development, but are also important for maintaining the stability and
      integrity of the expression profiles of different cell types. Until recently, the
      study of human disease has focused on genetic mechanisms rather than on non
      coding events. However, it is becoming increasingly clear that altered patterns
      of histone modifications can lead to several major pathologies. This review
      focuses on histone acetylation and its role in inflammatory gene expression.
      Interestingly, the expression and activity of enzymes that regulate this
      modification have been reported to be abnormal in the airways of patients with
      respiratory disease. Histone modifications, despite being heritable and stably
      maintained, are also potentially reversible and there is scope for the
      development of "epigenetic therapies" for disease.

PMID- 16977379
TI  - Gene expression profiling of skin and draining lymph nodes of rats affected with
      cutaneous contact hypersensitivity.
AB  - OBJECTIVES AND DESIGN: The present study aimed at a broad genome expression
      analysis of rat skin and draining lymph nodes affected with allergic contact
      dermatitis (ACD). METHODS: ACD was elicited in sensitized SD rats with 0.5% 2,4
      dinitrofluorobenzene on skin areas distant from the sensitization sites. Involved
      skin and lymph nodes were dissected 8 and 24 h after challenge. RNA was
      hybridized on Affymetrix GeneChips. Expression data were analyzed with the
      GeneSpring software. RESULTS: Expression of 1,882 out of 8,799 examined genes in
      skin or lymph nodes was significantly (p < or = 0.01) changed compared to levels
      in normal tissue. After an additional 2- fold filtering, four expression patterns
      were selected and interpreted. Prominently up-regulated genes were IL-6, CCR-5,
      CCL-2, CCL-3, CXCL-1, CXCL-10, TIMP-1, OX-40, calgranulin b, ST2, beta-defensin,
      iNOS, STAT-1, MMP-3, MMP-9, MMP-12, and MMP-13. CONCLUSIONS: In addition to
      previously reported transcript changes, the present findings suggest/support that
      plasma cells, mast cells, and a specific IFN-gamma pathway play a substantial
      role in the pathogenesis of ACD.

PMID- 16977380
TI  - Cytokine production profile of splenocytes derived from zymosan A-treated SKG
      mice developing arthritis.
AB  - OBJECTIVE: SKG mice have a point mutation of the zeta-associated protein of 70 kD
      (ZAP-70) and spontaneously develop a severe polyarthritis in the conventional
      condition, whereas they are healthy under the specific pathogen free (SPF)
      condition. The purpose of this study was to investigate the cytokine production
      from splenocytes in SKG mice developing arthritis under the SPF condition.
      MATERIAL: SKG and BALB/c mice were intraperitoneally injected with zymosan A
      under the SPF condition. Spleen was isolated 1, 2 or 8 weeks after the
      intraperitoneal injection of saline or zymosan A. Splenocytes were cultured with
      concanavalin A. Cytokine production and proliferation were measured 48 and 72 h
      after the culture. RESULTS: An intraperitoneal injection of zymosan A induced
      severe polyarthritis with increased levels of rheumatoid factor and interleukin 6
      (IL-6) only in SKG mice. Splenocytes from SKG mice did not proliferate well maybe
      because of less productivity of IL-2. The IL-4 production from splenocytes of SKG
      mice was higher, while interferon-gamma production was lower than those of BALB/c
      mice. An injection of zymosan A reduced the IL-4 production only in SKG mice.
      CONCLUSIONS: SKG mice do not develop arthritis under the SPF condition possibly
      because of a low proliferative activity of T cells and Th2-predominance.

PMID- 16977381
TI  - Lipid bodies: Structural markers of inflammatory macrophages in innate immunity.
AB  - OBJECTIVE AND DESIGN: The correlation between innate immune responses and
      formation of cytoplasmic lipid bodies (LBs) was investigated in vivo in
      inflammatory macrophages from rats infected with Trypanosoma cruzi, the
      intracellular parasite which causes Chagas' disease. MATERIAL AND METHODS: We
      used an experimental model of high-dose irradiation prior to infection, which
      depletes the humoral and cellular immune responses except for the phagocytic
      activity of macrophages. Rats, irradiated or not, were infected with T. cruzi and
      macrophages from different origins (peritoneum, heart, uterus) were studied by
      transmission electron microscopy (TEM). RESULTS: As documented by quantitative
      TEM, innate immune responses induced prominent formation, structural changes and
      intracellular interactions of LBs. LBs significantly increased their size and
      changed their osmiophilia in response to both infection alone and when
      macrophages were challenged with irradiation-induced increased parasite load.
      Remarkably, a consistent LB-phagolysosome association was identified. LBs were
      surrounding, attached to or internalized by phagolysosomes. CONCLUSIONS: We
      demonstrated that LBs are dynamic organelles notably involved in the host
      response to acute T. cruzi infection, an event that may be important for pathogen
      control during innate immunity. Our findings highlight LBs as structural markers
      of the innate immune responses in phagocytic cells.

PMID- 16977382
TI  - Estrogen attenuates vascular expression of inflammation associated genes and
      adhesion of monocytes to endothelial cells.
AB  - OBJECTIVE: Investigate effects of estrogen at gene expression and functional
      levels in vascular wall cells treated with bacterial lipopolysaccharide (LPS).
      MATERIALS AND METHODS: Aortic segments from ovariectomized mice were treated with
      LPS for 24 h in the absence or presence of 17beta-estradiol (E2). Gene activity
      was determined by Affymetrix microarray analysis and real-time RT-PCR. Adhesion
      of [3H]-thymidine labelled human THP-1 monocytes to mouse bEnd.3 endothelial
      cells was determined by measuring radioactivity of DNA from co-culture
      homogenates. RESULTS: Analysis of global gene expression profiles revealed that
      10 nM E2 attenuates LPS-induced (10 ng/ml) expression of genes coding for well
      known acute-phase proteins, such as alpha-trypsin inhibitor heavy chain 4, serum
      amyloid A3 and lipocalin 2. The E2-induced down-regulation of these three genes
      observed by microarray was confirmed by realtime RT-PCR. Treatment with 500 ng/ml
      LPS increased adhesion of monocytes to endothelial cells more than two fold.
      Importantly, LPS-induced monocyte adhesion was fully prevented by 50 nM E2.
      CONCLUSION: Estrogen reduces expression of acute-phase protein genes and inhibits
      LPS-induced moncocyte adhesion to endothelial cells, suggesting that estrogen
      might have a vasculoprotective effect via this mechanism.

PMID- 16977383
TI  - The effects of fructose-1,6-bisphosphate and dexamethasone on acute inflammation
      and T-cell proliferation.
AB  - OBJECTIVE AND DESIGN: Chronic glucocorticoid treatment is associated with
      pharmacological resistance. We investigated the auxiliary effects of fructose-1,6
      bisphosphate (FBP) on dexamethasone (DEX)-related modulation of inflammation and
      T-cell proliferation. METHODS: Acute inflammation (pleurisy) was induced by
      injection of carrageenan into the pleural cavity of rats that were treated in
      vivo with DEX s. c. and FBP i. p. Peripheral blood mononuclear cells were
      isolated and T-cell sensitivity to FBP and DEX was evaluated in vitro. RESULTS:
      FBP and DEX reduced the exudate volume, protein concentration and neutrophils in
      the pleural cavity. However no synergistic effects were observed when these
      compounds were tested simultaneously. In contrast, both compounds dose
      dependently and synergistically suppressed T-cell proliferation. CONCLUSION:
      These data suggest that FBP may be beneficial as auxiliary drug for the treatment
      of patients with acquired glucocorticoid resistance.

PMID- 16977384
TI  - Nano-structural bioactive gradient coating fabricated by computer controlled
      plasma-spraying technology.
AB  - The poor mechanical property of hydroxyapatite was the major problem for load
      bearing and implant coating in clinical applications. To overcome this weakness,
      a bioactive gradient coating with a special design composition of hydroxyapatite
      (HA), ZrO2, Ti, bioglass was developed. This 120 microm coating with an upper
      layer of 30-50 microm porous HA produced by computer controlled plasma spraying
      which maintained energy level of the plasma which ensure proper melting of
      powder. The crystal size of the coating was 18.6-26.2 nm. Transformation of t
      ZrO2 to m-ZrO2 reduced the thermal stress that weakened the coating and lowered
      down interfacial strength of the coating and metal substrate. Thermal stress of
      sprayed coating was 16.4 MPa which was much smaller than the sample without
      thermal treatment of 67.1 MPa. Interfacial strength between the coating and metal
      substrate was 53 MPa which is much higher than conventional Hydroxyapatite
      coating. Based on XRD analysis crystallinity of HA approached 98%. Therefore,
      high temperature treatment improved long term stability of the coating through
      improved crystallinity of hydroxyapatite and reduced other impure calcium
      phosphate phase.

PMID- 16977385
TI  - Effect of pH, temperature and Cl- concentration on electrochemical behavior of
      NiTi shape memory alloy in artificial saliva.
AB  - The cooperation of pH, temperature and Cl- concentration on electrochemical
      behavior of NiTi shape memory alloy in artificial saliva was studied using
      orthogonal test method. The results showed that the pitting potential for NiTi in
      artificial saliva decreased at low and high pH; at 25 degrees C, the pitting
      potential was the lowest compared to those at 10 degrees C, 37 degrees C and 50
      degrees C; when the Cl- concentration was not less than 0.05 mol/L the pitting
      potential decreased with the increase of Cl- concentration. The free corrosion
      potential of austenitic NiTi was lower than that of mixture of austenite and
      martensite.

PMID- 16977386
TI  - The effect of hyaluronan combined with KI3 complex (Hyiodine wound dressing) on
      keratinocytes and immune cells.
AB  - Hyiodine (high molecular weight hyaluronan combined with KI3 complex) is a new
      non-adhesive wound dressing which significantly improves the healing process. The
      aim of the study was to investigate the effects of Hyoidine on functional
      properties of isolated human keratinocytes and leukocytes, and on those of U937
      and HL60 cell lines. While KI3 complex inhibited the viability and proliferation
      of the cells tested, Hyiodine did not have any significant effect. The expression
      of CD11b, CD62L and CD69 on PMNL, monocytes and lymphocytes, as well as the
      oxidative burst of blood neutrophils, were not changed. On the contrary, Hyiodine
      inhibited the PMA-activated oxidative burst and significantly increased the
      production of IL-6 and TNF-alpha by lymphocytes. It was concluded that hyaluronan
      content of Hyiodine reduces the toxic effect of KI3 complex on cells and speeds
      up the wound healing process by increasing the production of inflammatory
      cytokines.

PMID- 16977387
TI  - Synthesis and characterization of cholesterol-poly(ethylene glycol)-poly(D,L
      lactic acid) copolymers for promoting osteoblast attachment and proliferation.
AB  - A novel cholesterol-poly(ethylene glycol)-poly(D,L-lactic acid) copolymer (CPEG
      PLA) has been synthesized as a potential surface additive for promoting
      osteoblast attachment and proliferation. The gel permeation chromatography (GPC)
      and nuclear magnetic resonance spectroscopy (NMR) results indicated the product
      had expected structure with low polydispersities in the range of 1.1-1.5. By
      blending the poly(D,L-lactic acid) (PLA) with CPEG-PLA, the surface of modified
      PLA membrane was investigated by atomic force microscopy (AFM), X-ray
      photoelectron spectroscopy (XPS) and contact angle. The results revealed the
      enrichment of PEG chain on the surface. Osteoblast cell line (MC3T3) was chosen
      to test the cell behavior on modified PLA membranes. The osteoblast test about
      cell attachment, proliferation, cell viability and cell morphology investigation
      on CPEG-PLA modified PLA substrates showed the CPEG-PLA with 15 and 5 ethylene
      glycol units promoted osteoblast attachment and growth, while the CPEG-PLA with
      30 ethylene glycol units prevent osteoblast adhesion and proliferation. This
      simple surface treatment method may have potentials for tissue engineering and
      other biomedical applications.

PMID- 16977388
TI  - An impedance study of two types of stainless steel in Ringer physiological
      solution containing complexing agents.
AB  - The effect of complexing agents EDTA and citric acid on the electrochemical
      behaviour of AISI 304 and orthopaedic stainless steels in Ringer physiological
      solution was investigated by potentiodynamic polarization method and
      electrochemical impedance spectroscopy (EIS). The content of Mo has a pronounced
      effect on the corrosion resistance, as evident by the broader passive range of
      the orthopaedic stainless steel containing Mo. The addition of complexing agents
      induces significant changes in polarization and impedance characteristics, i.e.,
      the shift of corrosion and breakdown potentials in a more negative direction, an
      increase in current density, and a significant decrease in charge transfer
      resistance. The results were interpreted by the formation of soluble complexes of
      metal ions with chelating agents, especially EDTA, which suppressed the formation
      of the outer Fe(III) layer of the passive film. The impact of complexing agent on
      the electrochemical parameters was found to be related to its concentration in
      electrolyte and the stability constant of the complex formed with the related
      metal ion.

PMID- 16977389
TI  - In vivo release of rhBMP-2 loaded porous calcium phosphate cement pretreated with
      albumin.
AB  - In this study, the release of rhBMP-2 loaded porous Ca-P cement was studied in
      vitro and in vivo. We hypothesized that adsorption sites of Ca-P ceramic with
      high affinity for rhBMP-2 can be blocked by pretreatment of the ceramic with
      albumin prior to rhBMP-2 loading, which would result in weaker rhBMP-2 binding
      and enhanced release of rhBMP-2. Preset porous Ca-P cement discs with a diameter
      of 6.35 mm (volume: 75 mm3) were pretreated by incubation in a solution of 10%
      rat serum albumin for 24 h or in ddH2O (control group) prior to administration of
      5 mug radiolabeled 131I-rhBMP-2. Release was assessed in vitro in phosphate
      buffered saline (PBS) and fetal calf serum and in vivo by longitudinal
      scintigraphic imaging of radiolabeled 131I-rhBMP-2 and gamma counting of
      dissected implants. In vitro release from pretreated discs was higher during the
      first day. For both formulations, release in PBS was limited compared to release
      in serum. In vivo release considerably exceeded in vitro release. In vivo release
      kinetics showed no significant difference of half-lives between pretreated and
      control discs. Both formulations showed sustained release during at least 4
      weeks. Ex vivo gamma counting of retrieved samples confirmed scintigraphic
      results and showed that the capsule and surrounding tissues only contained a
      minor fraction rhBMP-2. We conclude that 1. scintigraphy of 131I-labeled rhBMP-2
      provides a reliable method for longitudinal measurement of rhBMP-2 release
      kinetics in vivo. 2. albumin pretreatment of porous Ca-P cement does not results
      in relevant increase of initial release of rhBMP-2 in vivo, and 3. preset rhBMP-2
      loaded porous Ca-P cement discs exhibit one phase exponential release kinetics in
      the rat ectopic model, characterized by a retention of 20-30% after 4 weeks.

PMID- 16977390
TI  - Polysaccharide surface engineering of poly(D, L-lactic acid) via electrostatic
      self-assembly technique and its effects on osteoblast growth behaviours.
AB  - The objective of this study was to surface modify the poly (D, L-lactic acid)
      (PDLLA) films and assess the effects of the modified surfaces on the functions of
      osteoblasts cultured in vitro. A layer-by-layer (LBL) self assembly technique,
      was used leading to the formation of multilayers on the PDLLA film surfaces.
      Chitosan (Chi) and poly (styrene sulfonate, sodium salt) (PSS) were utilized as
      polycation and polyanion in this study, respectively. The layer structure was
      investigated by using X-ray photoelectron spectroscopy (XPS) and water contact
      angle measurement, respectively. XPS analysis displayed the presence of chitosan
      on PDLLA surface. A full coverage of coating with PSS/Chi layers was achieved on
      the PDLLA surface only after the deposition layers of PEI/(PSS/Chi)2. These
      results showed that PDLLA films could be modified with PSS/Chi pairs which may
      affect the biocompatibility of the modified PDLLA films. To confirm this
      hypothesis, cell proliferation, cell viability as well as alkaline phosphtase
      activity of osteoblasts on layer-by-layer modified PDLLA films as well as control
      samples were investigated in vitro. The proliferation of osteoblasts on modified
      PDLLA films was found to be greater than that on control (p < 0.05 and p < 0.01)
      after 1, 4 and 7 days culture, respectively. Cell viability measurement showed
      that the PSS/Chi modified PDLLA films have higher cell viability (p < 0.01) than
      control. Osteoblast differentiation function (ALP) on LBL-modified PDLLA film was
      found significantly higher (p < 0.01) than that of virgin PDLLA films. These data
      suggests that PSS/Chi pair was successfully employed to surface modify PDLLA film
      via a layer-by-layer technique, and enhanced its cell biocompatibility.

PMID- 16977391
TI  - Investigation of silica-iron-phosphate glasses for tissue engineering.
AB  - Phosphate-based glasses have previously been examined for tissue engineering
      applications, however they degrade rapidly in solution reducing its pH to below
      5. This study presents a series of phosphate-based glass compositions that
      degrade at a lower rate, allowing the pH to remain close to neutral in cell
      culture medium. The compositions investigated were P50Ca30Na(15-x)Fe5Si(x) where
      x = 0, 1, 3 and 5 mol%. The dissolution and effect on pH in distilled water and
      cell culture medium, and ion release in distilled water were investigated over 7
      days and MG63 cell attachment to glass fibres was observed after 24 hrs.
      Dissolution was much slower in cell culture medium (3% mass loss) compared to
      distilled water (50% mass loss), due to the large quantity of ions and pH buffer
      present. After 7 days, in cell culture medium the pH remained between 7 and 8.5,
      however the pH in distilled water fell to between 4 and 3, with the final pH
      being lower the greater the SiO2 content. Increasing the SiO2 content of the
      glass resulted in an increase in dissolution rate whilst the pH was maintained at
      7 in cell culture medium. The attachment and spreading of MG63 cells was observed
      on all compositions. These glass compositions may therefore be suitable for
      tissue engineering applications.

PMID- 16977392
TI  - Morphometric analysis of the effects of LactoSorb bioabsorbable plates on the
      craniofacial growth of rabbits using computed tomography.
AB  - This study investigated the effect of bioabsorbable plates and titanium
      microscrews on the growth of the craniofacial skeleton of rabbits (Oryctolagus
      cuniculus) in the neonatal period. All animals underwent surgery at seven weeks
      of age and were killed at twenty-four weeks. In the study group, LactoSorb plate
      and PROMM titanium microscrews were positioned across the coronal suture. In the
      control group, only PROMM titanium microscrews were attached to the cranium.
      Computed tomography was used to obtain morphometric measurements of volume.
      Results showed no significant intergroup (P < or = 0.05) or intragroup (control
      group P < or = 0.01; study group P < or = 0.05) differences in craniofacial
      volume. Under the experimental conditions of this study, bioabsorbable plates did
      not affect neonatal growth of craniofacial volume in rabbits.

PMID- 16977393
TI  - Tissue reaction and surface morphology of absorbable sutures after in vivo
      exposure.
AB  - Tissue reaction to suture materials depends mainly on how the polymer they are
      composed of interacts with the tissues. There are few in vivo studies evaluating
      the suture material modifications resulting from its interaction with tissues.
      This paper aimed to study rat subcutaneous tissue reaction to irradiated
      polyglactin 910, polydioxanone, poliglecaprone 25 and chromic gut and its
      correlation with the ultra-structural alterations the materials undergo. The
      histological alterations were studied on the 1st, 2nd, 3rd, 7th and 14th day
      after suture implantations. In these periods, the materials were removed from the
      tissues and their surfaces were analyzed by scanning electron microscopy.
      Irradiated polyglactin 910 stimulated the formation of multinucleated giant cells
      and its filaments underwent cleavage and dissolution. In potydioxanone, a few
      inflammatory cells and scar fibrosis was observed, and triangular cracks appeared
      on its surface. Around the poliglecaprone 25, a diffused infiltration of a few
      mononuclear cells and fibrosis was recorded and formation of craters was observed
      on its surface. Chromic gut induced necrosis and granulation tissue and underwent
      dissolution in the tissues during the studied periods. In this study, it was
      observed that suture materials induced differentiated tissue reactions and
      morphologic surface changes, suggesting that indications should be
      individualized.

PMID- 16977394
TI  - [Prescription of generic drugs in general practice. Results of a survey of
      general practitioners].
AB  - BACKGROUND AND PURPOSE: Switching brand-name drugs to generics is reasonable and
      desired for economic reasons. Few data exist about problems, if any, during the
      switching in general practice. In this survey, the view of general practitioners
      (GPs) should be ascertained. METHODS: GPs in five counties in the German federal
      states Thuringen and Baden-Wurttemberg, who took part in a study on generic drug
      prescribing, were asked to complete a questionnaire about experiences and
      attitudes toward generic drug prescription. RESULTS: A total of 195 (84%) of 233
      GPs answered the questionnaire. Two thirds (127/195) stated, that brands and
      generics are pharmacologically equivalent. Many of these GPs estimated to
      prescribe generic drugs in > 50% of instances; fewer doctors did so, if they had
      doubts as to the equivalence of generics (65% vs. 46%; p < 0.05). Nearly 8%
      reported generics being less effective, and 10% observed new adverse effects
      after switching. Many GPs appointed the following barriers: cooperation with
      hospitals and colleagues (86%), GP's lack of time (68%), and communication
      problems with the patient (50%). GPs estimated that > 10% of patients strictly
      reject generic drugs. CONCLUSION: An optimized cooperation between GPs and
      hospital physicians could facilitate the consumption of generic potential in
      pharmacotherapy. Reasons for the obvious contrast between the proven
      pharmacological equivalence of brand-name and generic drugs and the problems
      encountered after switching reported by GPs should be further studied.

PMID- 16977395
TI  - [Are competitions an appropriate instrument for youth smoking cessation? A 1-year
      follow-up of the Germany-wide "Smoke-free 2004" campaign].
AB  - BACKGROUND: In 2004, the German Cancer Research Center ("Deutsches
      Krebsforschungszentrum" [DKFZ]), collaborating with the Federal Center for Health
      Education (""Bundeszentrale fur gesundheitliche Aufklarung" [BZgA]) and supported
      by the World Health Organization (WHO), carried out a population-related smoking
      cessation campaign entitled "Rauchfrei 2004" ("Smoke-free 2004"). Using mass
      media communication, the campaign was intended to motivate as many smokers as
      possible to quit smoking for at least 4 weeks, so as to achieve, ideally,
      complete cessation of tobacco consumption. This prevention campaign explicitly
      included juvenile smokers. METHODS: Within a 1-year follow-up survey, a 1/3
      random sample was taken from a total of 4,358 juvenile participants whose smoking
      status by the end of the competition and 1 year later was evaluated according to
      international standards. RESULTS: 42% of juvenile participants named monetary
      reasons, 33% health-related reasons as their chief motivation for participating
      in the competition. 61% of young adults questioned stated that they were
      abstinent at the end of the competition, i.e., at least for 4 weeks. 1 year
      later, 19% of juvenile participants stated to be nonsmokers. 12% of them stated
      to have been continuously abstinent for 12 months after the start of the
      competition. CONCLUSION: This publication is the first scientific evaluation of
      juvenile participation in a competition-based smoking cessation campaign.
      Although some methodological restrictions need to be taken into account,
      abstinence rates determined according to internationally applied WHO evaluation
      guidelines are significantly higher than the secular trend. Thus, the prevention
      approach presented here appears to be similarly effective as alternative
      intervention programs that tend to be more expensive.

PMID- 16977396
TI  - [Problems and chances of the application of systemically acting drugs via the
      lung].
AB  - As a consequence of the development of drugs and other biologically active
      substances such as peptides or proteins, new ways of application for therapeutic
      use offer new therapeutic possibilities. Today, the predominant way of parenteral
      application is injection. Growing evidence suggests that some substances may be
      applied via inhalation. Nevertheless, inhalative application of drugs, although
      possible, is not very well supported by scientific data until now. This paper
      summarizes the present knowledge about transport of higher-molecular drugs across
      the pulmonary epithelium and deals with the problems of this method of
      application as well.

PMID- 16977397
TI  - [Zygomycosis after hematogeneic stem cell transplantation--a current problem?].
AB  - Zygomycoses are rare but often lethal mold infections predominantly affecting
      immunocompromised patients. Over the last years, several tertiary-care cancer
      centers reported an increase in the incidence of zygomycete infections in
      allogeneic blood stem cell transplant recipients. These observations are based on
      a small number of patients and should be considered in the context of a decades
      long increase of mold infection rates. Diagnostic obstacles, including the
      difficult discrimination from the tenfold more frequent aspergilloses, may
      confound the reported incidences of zygomycete infections. These may be due to
      changes in frequency, severity and management of graft-versus-host disease
      promoting filamentous fungal infections, including zygomycoses. Hospitals
      applying long-term voriconazole prophylaxis in high-risk patients report a
      significant decrease in aspergillosis rates since the drug became available in
      2001. The observation of increased frequencies of zygomycete infections during
      this period of time is not based on prospective evaluations. Therefore, the
      causes of these findings remain a matter of debate. Current multicenter trials on
      antifungal prophylaxis in high-risk patients promise to generate reliable data on
      the protective effect of antifungals active against molds, and the incidence of
      zygomycete infections in a controlled setting.

PMID- 16977399
TI  - [Differential diagnosis of hyperhidrosis].

PMID- 16977398
TI  - [Prevention of type 2 diabetes in Germany. Ideas, evidence, implementation].
AB  - One of the challenges in clinical diabetology today is to develop and implement
      diabetes prevention management programs for clinical practice. Recent studies
      have convincingly demonstrated that lifestyle intervention, addressing diet and
      exercise, as well as pharmacological preventive strategies reduce the risk of
      progressing from impaired glucose tolerance to diabetes. With respect to the
      worldwide burden of diabetes, these studies offer a compelling evidence base for
      the important translation of the research findings into community-based
      prevention strategies and the development of a national diabetes prevention
      program. The work group "diabetes prevention" of the German Diabetes Association
      together with the National Action Forum Diabetes and the German Diabetes
      Foundation developed a concept for a national program. This comprises a three
      step intervention: in a first step individuals at high risk of developing type 2
      diabetes are identified. The second step provides an intensive group intervention
      to prevent diabetes, and in a third step continuous intervention should
      facilitate motivation maintenance and evaluation. This third step is the crucial
      step to maintain the effect in changing lifestyle. Recently, a compendium for
      diabetes prevention was developed as a practical guideline explaining how to
      implement prevention programs. This guideline also includes the structure of a
      national prevention program with a prevention manager having a central role in
      the concept and suggestions for evaluation and quality control.

PMID- 16977400
TI  - [Angiosarcoma of the liver as a rare cause of rapidly progressive liver failure].
AB  - BACKGROUND: Angiosarcoma of the liver is a rare, highly malignant and sometimes
      diffusely infiltrating vessel tumor with rapid progression and poor prognosis.
      CASE REPORT: A 46-year-old male patient with rapidly progressive liver failure,
      initially regarded as decompensation of known alcoholic liver cirrhosis, is
      reported. The patient was referred to the authors' center for evaluation of liver
      transplantation, but a massive weight loss despite long absence of any alcohol
      intake raised the suspicion of a malignant disease. The abdominal ultrasound
      examination showed a massive hepatomegaly with an extremely inhomogeneous echo
      structure as well as moderate ascites. A following MRI demonstrated diffuse focal
      contrast enhancement in the entire liver parenchyma, confirming diffuse
      infiltration of the organ by a malignant tumor. In addition, MRI was suspicious
      of bone metastases. The usual tumor markers were normal. Sonographically guided
      percutaneous liver biopsy established the diagnosis of a malignant vascular tumor
      with diffuse infiltration of the liver parenchyma. 3 days later the patient died
      of uncontrollable bleeding from esophageal varices. Macroscopic examination of
      the liver during autopsy showed multiple lacunae filled with blood. Therefore,
      the differential diagnosis of a peliosis hepatis was raised. However, histology
      confirmed the diagnosis of a malignant angiosarcoma with diffuse osseous
      metastases. CONCLUSION: A diffuse infiltration of the liver by an angiosarcoma in
      the absence of any definite lesions may lead to a substantial delay of the
      diagnosis. The only relevant differential diagnosis in this case is the equally
      rare peliosis hepatis.

PMID- 16977401
TI  - [DRG and coding: debatable comorbidities].

PMID- 16977402
TI  - [The competence network for congenital heart defects. Networking instead of
      isolated efforts for optimized research and care].
AB  - Congenital heart defects (CHD) are the most common congenital malformation; there
      is no clearly defined clinical picture. Although, thanks to medical progress,
      most of those affected survive into adulthood, they remain chronically ill
      throughout their lives and require specific care. By enabling nationwide
      cooperation and interdisciplinary research, the Competence Network for Congenital
      Heart Defects can provide and optimize this care. Clinical studies concerning
      clinical manifestations and recent diagnostic and treatment options can make use
      of the collected data. Being the core project of the Network, the National
      Register for congenital heart defects (registered association) registers all
      patients with a CHD throughout Germany. This data provides a basis for
      epidemiologic studies concerning quality of life and psychosocial aspects. Thus,
      integral care and swift transfer of knowledge between science and practice can be
      achieved. Meanwhile, pediatric guidelines could be developed and raised to S2
      level. Additionally, the Register's results allow an assessment of the present
      situation of cardiac malformations, which is to be further evaluated in current
      studies. Particular attention is paid to the prevalence of CHD and adult
      patients' needs. In the long term, the concept of integrated care, and especially
      the idea of multidisciplinarity, is to be realized within the scope of a "health
      care database". All in all, the Competence Network for Congenital Heart Defects
      plays a substantial part in detecting needs and deficits of the current care for
      patients with CHD and helps developing strategies for an adequate and efficient
      care, while guaranteeing a high degree of transparency for those concerned.

PMID- 16977403
TI  - [Illness and death of Wolfgang Amadeus Mozart (1756-1791). A contribution to the
      Mozart Year 2006].
AB  - In the Mozart year 2006 also medicine has to deal with the music genius W.A.
      Mozart. It has been intensely discussed for a long time whether Mozart was
      poisoned, whether he deceased from a certain illness, or by self-medication
      and/or medical procedures. Consequently, his death caused wild speculations and
      adventurous assertions. Many authors assume that Mozart was a chronically ill man
      all his life. However, most of Mozart's described illnesses were harmless, and
      his unbelievable amount of work proves his extraordinary efficiency. The exact
      cause of death remains speculative. The story of a tall stranger dressed in
      somber gray who assigned Mozart to write a Requiem Mass and the circumstances of
      Mozart's funeral have additionally contributed to the generation of legends.
      However, if one gathers all known facts, there is no evidence that Mozart was
      murdered, and the exact cause of his death remains unclear.

PMID- 16977423
TI  - Influence of chronic cardiovascular disease and hospitalisation due to this
      disease on quality of life of community-dwelling elderly.
AB  - The aim of this study was to describe the impact of chronic cardiovascular
      disease (CVD) and hospitalisation due to this disease on quality-of-life (QOL) in
      community-dwelling elderly. The study was carried out in the three age- and
      gender-matched groups of older subjects: 100 elderly without CVD, 100 elderly
      with CVD and 100 patients actually hospitalised for the cardiologic reasons. The
      assessment included demographic and social variables, health status, nutritional
      state, physical activity (PA), physical and cognitive function. QOL was assessed
      with the Euroqol 5D questionnaire. Presence of CVD per se detracted from QOL only
      moderately, increasing the subjective perception of pain/discomfort.
      Hospitalisation was connected with the reduction of the majority of QOL
      dimensions and the decrease of rating on visual analogue scale (VAS). When taking
      into account all confounders the presence of CVD did not significantly contribute
      to overall QOL, while hospitalisation decreased the usual activity dimension of
      QOL and VAS, but interestingly, improved the perception of well-being in relation
      to anxiety/depression. Variables that most powerfully detracted from QOL were
      lower functional status, higher number of medications used, poor nutritional
      state, low habitual PA and above all, depression. These findings suggest that
      physical and cognitive function as well as regular PA may affect QOL more in
      community-dwelling elderly than the presence of CVD or even need of
      hospitalisation.

PMID- 16977404
TI  - Recombinant vesicular stomatitis virus as an HIV-1 vaccine vector.
AB  - Recombinant vesicular stomatitis virus (rVSV) is currently under evaluation as a
      human immunodeficiency virus (HIV)-1 vaccine vector. The most compelling reasons
      to develop rVSV as a vaccine vector include a very low seroprevalence in humans,
      the ability to infect and robustly express foreign antigens in a broad range of
      cells, and vigorous growth in continuous cell lines used for vaccine manufacture.
      Numerous preclinical studies with rVSV vectors expressing antigens from a variety
      of human pathogens have demonstrated the versatility, flexibility, and potential
      efficacy of the rVSV vaccine platform. When administered to nonhuman primates
      (NHPs), rVSV vectors expressing HIV-1 Gag and Env elicited robust HIV-1-specific
      cellular and humoral immune responses, and animals immunized with rVSV vectors
      expressing simian immunodeficiency virus (SIV) Gag and HIV Env were protected
      from AIDS after challenge with a pathogenic SIV/HIV recombinant. However, results
      from an exploratory neurovirulence study in NHPs indicated that these prototypic
      rVSV vectors might not be adequately attenuated for widespread use in human
      populations. To address this safety concern, a variety of different attenuation
      strategies, designed to produce a range of further attenuated rVSV vectors, are
      currently under investigation. Additional modifications of further attenuated
      rVSV vectors to upregulate expression of HIV-1 antigens and coexpress molecular
      adjuvants are also being developed in an effort to balance immunogenicity and
      attenuation.

PMID- 16977424
TI  - A rice dehydration-inducible SNF1-related protein kinase 2 phosphorylates an
      abscisic acid responsive element-binding factor and associates with ABA
      signaling.
AB  - By a differential cDNA screening technique, we have isolated a dehydration
      inducible gene (designated OSRK1) that encodes a 41.8 kD protein kinase of SnRK2
      family from Oryza sativa. The OSRK1 transcript level was undetectable in
      vegetative tissues, but significantly increased by hyperosmotic stress and
      Abscisic acid (ABA). To determine its biochemical properties, we expressed and
      isolated OSRK1 and its mutants as glutathione S-transferase fusion proteins in
      Escherichia coli. In vitro kinase assay showed that OSRK1 can phosphorylate
      itself and generic substrates as well. Interestingly, OSRK1 showed strong
      substrate preference for rice bZIP transcription factors and uncommon cofactor
      requirement for Mn(2+) over Mg(2+). By deletion of C-terminus 73 amino acids or
      mutations of Ser-158 and Thr-159 to aspartic acids (Asp) in the activation loop,
      the activity of OSRK1 was dramatically decreased. OSRK1 can transphosphorylate
      the inactive deletion protein. A rice family of abscisic acid-responsive element
      (ABRE) binding factor, OREB1 was phosphorylated in vitro by OSRK1 at multiple
      sites of different functional domains. MALDI-TOF analysis identified a
      phosphorylation site at Ser44 of OREB1 and mutation of the residue greatly
      decreased the substrate specificity for OSRK1. The recognition motif for OSRK1,
      RQSS is highly similar to the consensus substrate sequence of AMPK/SNF1 kinase
      family. We further showed that OSRK1 interacts with OREB1 in a yeast two-hybrid
      system and co-localized to nuclei by transient expression analysis of GFP-fused
      protein in onion epidermis. Finally, ectopic expression of OSRK1 in transgenic
      tobacco resulted in a reduced sensitivity to ABA in seed germination and root
      elongation. These findings suggest that OSRK1 is associated with ABA signaling,
      possibly through the phosphorylation of ABF family in vivo. The interaction
      between SnRK2 family kinases and ABF transcription factors may constitute an
      important part of cross-talk mechanism in the stress signaling networks in
      plants.

PMID- 16977425
TI  - Morphological and molecular characterisation of Paranoplocephala buryatiensis n.
      sp. and P. longivaginata Chechulin & Gulyaev, 1998 (Cestoda: Anoplocephalidae) in
      voles of the genus Clethrionomys.
AB  - A new species, Paranoplocephala buryatiensis n. sp. (Cestoda:Anoplocephalidae),
      is described from the grey-sided vole Clethrionomys rufocanus (Sundevall) in the
      Republic of Buryatia (Russian Federation) and compared with P. longivaginata
      Chechulin & Gulyaev, 1998, a parasite of the red vole C. rutilus (Pallas) in the
      same region. P. buryatiensis n. sp. and P. longivaginata both have an
      exceptionally long vagina and cirrus, unique features among known species of
      Paranoplocephala Luhe, 1910. The new species differs from P. longivaginata
      primarily by its wider and more robust body, lower length/width ratio of mature
      proglottides, tendency of testes to occur in two separate groups, seminal
      receptacle of a different shape and the position of the cirrus-sac with respect
      to the ventral longitudinal osmoregulatory canal. The cytochrome oxidase subunit
      I (COI) sequence data support the independent status of these species, and show
      that they form a monophyletic assemblage within Paranoplocephala (sensu lato).
      Assuming cospeciation, an indirect calibration using host speciation dates
      estimated a rate of mtDNA substitution of 1.0-1.7% pairwise (0.5-0.85% per
      lineage) sequence divergence per million years. A faunistic review of
      Paranoplocephala species in C. rufocanus and C. rutilus in the Holarctic region
      is presented.

PMID- 16977426
TI  - The occurrence of the Japanese species Dinosoma lophiomi Toman, 1973 (Digenea:
      Hemiuridae) in Lophius piscatorius (Teleostei) from the western Mediterranean.
AB  - Hemiurid worms from the stomach of the angler Lophius piscatorius off Corsica are
      described and considered to belong to a Japanese species, Dinosoma lophiomi
      Toman, 1973, which was originally described from an Indo-Pacific lophiid host.
      The apparent disjunctive distribution of this species and apparent differences in
      the terminal genitalia between the European and Japanese specimens are discussed.
      This is the first record of Dinosoma Manter, 1934 from the Mediterranean Sea. The
      validity of diagnostic features of Adinosoma Manter, 1947 is commented upon, and
      lists of records of species of Dinosoma and digeneans from L. piscatorius in the
      Western Mediterranean are included.

PMID- 16977428
TI  - Mapping the antigenic determinants and reducing the immunogenicity of
      trichosanthin by site-directed mutagenesis.
AB  - Trichosanthin (TCS) is a type I ribosome-inactivating protein (RIP) possessing
      multiple pharmacological properties. One of its interesting properties is to
      inhibit human immunodeficiency virus (HIV) replication but its strong
      immunogenicity has limited the repeated clinical administration. To map the
      antigenic determinants and reduce the immunogenicity of TCS, two potential
      antigenic sites (YFF81-83 and KR173-174) were identified by computer modeling,
      and then three TCS mutants namely TCS(YFF81-83ACS), TCS(KR173-174CG), and TCS(YFF
      KR) were constructed by site-directed mutagenesis. The RI activity and DNase-like
      activity of the three constructed TCS mutants were similar to natural TCS but
      with much lower immunogenicity. Results suggested that the two selected sites are
      all located at or near the antigenic determinants of TCS. In toxicity studies,
      the LD(50) of the three TCS mutants was not different from natural TCS. These
      findings would be useful in designing a better therapeutic agent for AIDS.

PMID- 16977429
TI  - Morphological features of osteoclasts derived from a co-culture system.
AB  - The interaction between the receptor activator of NfKB (RANK) and its ligand
      receptor activator of NfKB ligand (RANKL) has recently been proven to be pivotal
      for osteoclast differentiation and activation. The influence of RANK-RANKL
      signaling on osteoclast formation was established by co-culturing murine
      osteoblasts (type CRL-12257) and murine mononuclear monocytes (RAW 264.7). The
      aim of the present study was to examine, by means of morphological techniques,
      the interaction between these two cell lines grown in the absolute absence of
      exogenous cytokines and other stimulating factors. Moreover, we wanted to show
      that our model could provide a system to analyze the bone resorption process.
      Mineralized matrix induced morphological changes of osteoclasts (OC) by the
      formation of organized ruffled-border and a large number of secondary lysosomal
      vesicles. On the contrary, OC grown on glass coverslips without dentin showed no
      organized ruffled border or secondary lysosomes. The study of the relationship
      between these two cell types could establish new approaches for a potential
      pharmacological control of these cell types and tissues in health and disease.

PMID- 16977430
TI  - Using physiological models and decision theory for selecting appropriate
      ventilator settings.
AB  - OBJECTIVE: To present a decision support system for optimising mechanical
      ventilation in patients residing in the intensive care unit. METHODS:
      Mathematical models of oxygen transport, carbon dioxide transport and lung
      mechanics are combined with penalty functions describing clinical preference
      toward the goals and side-effects of mechanical ventilation in a decision
      theoretic approach. Penalties are quantified for risk of lung barotrauma,
      acidosis or alkalosis, oxygen toxicity or absorption atelectasis, and hypoxaemia.
      RESULTS: The system is presented with an example of its use in a post-surgical
      patient. The mathematical models describe the patient's data, and the system
      suggests an optimal ventilator strategy in line with clinical practice.
      CONCLUSIONS: The system illustrates how mathematical models combined with
      decision theory can aid in the difficult compromises necessary when deciding on
      ventilator settings.

PMID- 16977431
TI  - Three-dimensional imaging of pigment epithelial detachment in age-related macular
      degeneration using optical coherence tomography, retinal thickness analysis and
      topographic angiography.
AB  - INTRODUCTION: New diagnostic tools such as the retinal thickness analyzer (RTA),
      optical coherence tomography (OCT), and topographic angiography (TAG) were
      introduced into clinical ophthalmology during the last years giving the examiner
      new insights into anatomical and functional aspects of macular disease. In this
      study, advantages and disadvantages of the new imaging methods have been
      evaluated in patients with serous (sPED) and fibrovascular pigment epithelial
      detachments (fPED) secondary to age-related macular degeneration (AMD). METHODS:
      TAG, using fluorescein angiography (FA), provides a three-dimensional profile of
      the fluorescein pattern based on the analysis of a set of 32 confocal images over
      a depth of 4 mm. RTA and OCT provide cross-sectional images of the neurosensory
      retina and the retinal pigment epithelium-choriocapillary complex as well as
      retinal thickness data encoded in a false color map. We compared and evaluated
      these modalities in 15 patients with fPED and 15 patients with sPED secondary to
      AMD. RESULTS: In patients with classic fPED, TAG detected neovascular structures
      and delineated their configuration. In sPEDs, pooling of extravascular fluid was
      detected in a dome-shaped configuration. OCT provided detailed information on the
      neurosensory retina's structures but failed to detect the neovascular membrane in
      fPED. Mapping the retinal thickness, RTA and OCT both failed to detect the PED
      and showed typical algorithm error-based patterns. CONCLUSION: TAG OCT and RTA
      are useful imaging modalities in the evaluation of AMD cases. TAG visualizes the
      vascular configuration, dynamic perfusion, and leakage changes. OCT and RTA are
      able to complementarily document intra-, subretinal, and sub-RPE fluid
      accumulation secondary to CNV. However, OCT seems to be more efficient in imaging
      AMD-related pathologies than RTA, as this modality is often compromised by intra-
      or subretinal structural abnormalities. Nevertheless, all modalities may provide
      further valuable insight into AMD pathogenesis, enhance diagnostic quality, and
      improve the assessment of therapeutic effects.

PMID- 16977432
TI  - Fluorescence in situ hybridization using the subtelomeric 11q probe as a
      diagnostic tool for congenital thrombocytopenia.

PMID- 16977433
TI  - [Resection of infected achilles tendon. Results after soft tissue coverage
      without tendon reconstruction].
AB  - BACKGROUND: Structural full-thickness defects of the Achilles tendon represent a
      severely disabling injury which should be treated by reconstruction. This study
      presents functional outcomes from standardised follow-up of non-reconstructed
      Achilles tendons with soft tissue coverage alone. PATIENTS AND METHODS: Seven
      patients were treated with various techniques of soft tissue reconstruction
      without restoration of the Achilles tendon. After a mean of 11 months
      postoperatively, the lower extremity was evaluated generally with regard to
      function, AOFAS score (ankle and hindfoot), and isokinetic torque testing by the
      Biodex system. RESULTS: All patients showed high mobility, muscle strength, and
      range of motion at follow-up. The average AOFAS score was 84.7 (maximum 100), and
      the torque loss in plantar flexion was 44.5% on average compared to the
      uninvolved side and thus comparable with results after secondary tendon
      reconstruction. CONCLUSION: After complete loss of the Achilles tendon,
      compensatory techniques can hinder significant loss of torque and endurance,
      compared with secondary tendon reconstruction, allowing unsupported mobility and
      even top athletic performance.

PMID- 16977434
TI  - Identifying genes underlying skin pigmentation differences among human
      populations.
AB  - Skin pigmentation is a human phenotype that varies greatly among human
      populations and it has long been speculated that this variation is adaptive. We
      therefore expect the genes that contribute to these large differences in
      phenotype to show large allele frequency differences among populations and to
      possibly harbor signatures of positive selection. To identify the loci that
      likely contribute to among-population human skin pigmentation differences, we
      measured allele frequency differentiation among Europeans, Chinese and Africans
      for 24 human pigmentation genes from 2 publicly available, large scale SNP data
      sets. Several skin pigmentation genes show unusually large allele frequency
      differences among these populations. To determine whether these allele frequency
      differences might be due to selection, we employed a within-population test based
      on long-range haplotype structure and identified several outliers that have not
      been previously identified as putatively adaptive. Most notably, we identify the
      DCT gene as a candidate for recent positive selection in the Chinese. Moreover,
      our analyses suggest that it is likely that different genes are responsible for
      the lighter skin pigmentation found in different non-African populations.

PMID- 16977435
TI  - Can pyloromyotomy for infantile hypertrophic pyloric stenosis be performed in any
      hospital? Results from two teaching hospitals.
AB  - In order to document the incidence of perioperative complications in patients
      with infantile hypertrophic pyloric stenosis, a descriptive cohort study was
      performed in two teaching hospitals in the Netherlands. One hospital specialized
      in pediatric surgery and the other was a general surgery teaching hospital. All
      consecutive infants who underwent pyloromyotomy for the diagnosis hypertrophic
      pyloric stenosis in both hospitals between 1998 and 2002 were included. The
      children were diagnosed and treated according to a standard protocol. From all
      charts, complications durante- and post-operationem were recorded. A total of 256
      pyloromyotomies were performed. Registered perioperative complications were
      duodenal mucosal perforation (n=6; 2%). Perioperatively unrecognized duodenal
      mucosal perforation occurred four times (1%). One re-operation was performed for
      an incomplete pyloromyotomy (0.3%). Persistent vomiting after the operation
      occurred in 18 children (7%). A large majority of postoperative complications
      were wound infections (n=16; 6%), 12 after right upper quadrant incision and 4
      after umbilical incision; most of them were treated with antibiotics and/or
      incision for drainage of an abscess. An incisional hernia occurred four times.
      Prolonged vomiting was the only postoperative complication that differed
      significantly between the two teaching hospitals. The overall percentages of
      complications were equal to complication rates in literature, and since there
      were no extensive differences in major complications between the two teaching
      hospitals in this study, we can conclude that pyloromyotomy can be performed
      safely in specialized centers and in general centers provided with a
      multidisciplinary team.

PMID- 16977436
TI  - Monozygotic twins concordant for idiopathic thrombocytopenic purpura and
      discordant for systemic lupus erythematosus and lupus nephritis.
AB  - We report on identical twin sisters with systemic lupus erythematosus and lupus
      nephritis after initial presentation as idiopathic thrombocytopenic purpura. The
      patients had diverse clinical signs, symptoms and pathological findings of lupus
      nephritis. The changes in antinuclear antibodies and anti-double-stranded DNA
      antibodies were quite different. We conclude that even with an identical genetic
      background and the same environment, the expression of systemic lupus
      erythematosus and subsequent progression to lupus nephritis in twins was
      distinct, and antinuclear antibodies and anti-double-stranded DNA antibodies are
      helpful for clinical monitoring.

PMID- 16977437
TI  - Benign pancreatic hyperenzymemia in children.
AB  - One of us recently described chronic pancreatic hyperenzymemia in the absence of
      pancreatic or other disease in adult subjects. The aim of the present study was
      to describe this form of pancreatic hyperenzymemia in children. The study
      involved 15 children with this condition seen from September 1996 to December
      2004. After initial evaluation, each child was seen by us once annually until the
      end of the study. Each check-up included serum amylase (normal values 20-220
      IU/L), pancreatic isoamylase (17-115 IU/L) and lipase (24-270 IU/L)
      determinations as well as abdominal ultrasound. In six children, fecal elastase
      was also determined. At the initial assessment, 13 of the 15 children had
      abnormal serum increases in all three enzymes, one showed an increase only in
      lipase, and in the remaining child all three enzymes were present in normal
      concentrations. These latter two children had had abnormally elevated levels of
      all enzymes at the examination performed before this study began. During follow
      up, enzyme concentrations remained abnormally elevated, although with wide
      fluctuations and transient normalizations. Considering the highest values of
      enzymes found in the various examinations performed during this study, the
      increase over the upper normal limit was in the range of 1.5- to 5.2-fold for
      amylase, 2.2-to 8.0-fold for pancreatic isoamylase, and 2.0- to 15.4-fold for
      lipase. Fecal elastase was normal in the six children in whom it was measured. No
      child had evidence of pancreatic or other disease, either at initial evaluation
      or during follow-up. The results of this study describe benign pancreatic
      hyperenzymemia in children. Although it is a benign condition, awareness of it is
      important to avoid unnecessary concern and multiple diagnostic procedures.

PMID- 16977438
TI  - Relationships between cotinine, lower respiratory tract infection, and eosinophil
      cationic protein in children.
AB  - INTRODUCTION: The aim of this study was to investigate the effect of passive
      smoking on urine eosinophil cationic protein (u-ECP) in children with lower
      respiratory tract infections (LRTI). METHOD: This was a case-control study. The
      study cohort consisted of 150 children with LRTI (case group) and 150 healthy
      children (control), all from a urban setting. The statistical parameters were: a
      minimum of 139 children for a 95% confidence interval (95% CI), 80% power, and a
      possible exposure prevalence of 50%. The u-cotinine and u-ECP levels were
      measured by radioimmunoassay and fluoroimmunoassay methods, respectively. Data
      were analyzed by the McNemar chi-square test, t-test, and Pearson correlation.
      RESULTS: When the generally accepted cut-off level of 30 ng/mg urinary
      cotinine/creatinine was applied, 87.3% of the children with LRTI and 84.7% of
      healthy children were passive smokers. Using a cut-off level of 60 ng/mg, passive
      smoking increased the prevalence of LRTI by 4.7-fold (p=0.000). The mean u-ECP
      values were significantly higher in the case group than in the healthy control
      group (p=0.018). A positive association was found between u-cotinine and u-ECP
      values in children with LRTI (p=0.034). CONCLUSION: The results of this study
      indicate that passive smoking may play an important role in the development of
      respiratory infections and can cause airway inflammation in children with
      existing LRTI.

PMID- 16977439
TI  - Aortic intima-media thickness and lipid profile in macrosomic newborns.
AB  - Macrosomia is associated with alterations in lipoprotein composition and
      concentration at birth. Exposure to diabetes in utero has been established as a
      significant risk factor for some of the components of metabolic syndrome. The aim
      of this study was to investigate the effect of macrosomia on lipid metabolism,
      aortic intima-media thickness (aIMT) and subsequent atherogenic risk in newborn
      infants. Aortic intima-media thickness was measured in 40 macrosomic neonates of
      diabetic mothers (group A), 30 macrosomic neonates of healthy mothers (group B)
      and 30 healthy neonates (group C). Lipid profile was determined in all infants
      and their mothers. Mean aIMT was significantly higher in macrosomic neonates of
      diabetic and healthy mothers (0.56+/-0.06 and 0.49+/-0.03 mm respectively) than
      in controls (0.39+/-0.03 mm). Weight-adjusted aIMT in macrosomic neonates of
      diabetic mothers (0.129+/-0.013 mm/kg) was significantly higher than in groups B
      and C (0.114+/-0.008 and 0.113+/-0.011 mm/kg respectively). There were
      significant alterations of total serum, high-density lipoprotein (HDL), very low
      density lipoprotein (VLDL) cholesterols and triglyceride levels in the macrosomic
      neonates of diabetic mothers compared with controls. Macrosomia was associated
      with increased lipid concentrations. Macrosomic neonates of diabetic mothers have
      significantly higher aIMT with lipid alterations. This may play a role in the
      pathogenesis of atherosclerosis in adult life.

PMID- 16977440
TI  - [The educational program for the management of psoriasis vulgaris according to
      the rules of the Task Force on Dermatological Prevention: current status].
AB  - BACKGROUND: Psoriasis vulgaris is a chronic inflammatory skin disease with a
      substantial impairment of quality of life. Interdisciplinary outpatient
      educational programs are an innovative supplementary therapy form for the
      management of this disorder. SUBJECTS AND METHODS: The Task Force on
      Dermatological Prevention developed a concept for outpatient instruction of
      psoriasis patients. Five 2-hour classes by dermatologists,
      psychotherapists/psychologists and dieticians focus on central topics relevant
      for the patients and the management of the disease. RESULTS: The results
      presented are based on own experiences with this educational program. The
      interdisciplinary program is accepted very well and seen as helpful by the
      concerned. A structure analysis of the effects in a greater number of cases is a
      current goal. In some areas, health insurance companies are paying for the
      classes. CONCLUSION: The educational program for the management of psoriasis
      vulgaris according to the rules of the Task Force on Dermatological Prevention is
      a supplement of the treatment of patients with this chronic skin disease. Broader
      implementation in Germany is desirable.

PMID- 16977441
TI  - [Allergens for specific immunotherapy: authorization and quality criteria of the
      Paul-Ehrlich-Institut].
AB  - The marketing authorization of allergen preparations for specific immunotherapy
      (SIT) for subcutaneous injection (SCIT) and sublingual immunotherapy (SLIT) at
      the Paul-Ehrlich-Institut (PEI) insures that the quality, safety, and efficacy of
      these medicinal products is proven. As finished products, these medicinal
      products are subject to official batch control tests, which provide evidence that
      only those products are marketed which conform to the specifications laid down in
      the marketing authorization procedure. Products for SIT prepared for a patient on
      the basis of the physician's prescription - so-called named patient products -
      cannot be subjected to a marketing authorization review. Therefore, they are not
      subject to the pharmaco-surveillance by the PEI regarding quality, safety and
      efficacy. This article describes the different marketing authorization procedures
      in the European Union (EU) and addresses the problems related to the marketing
      authorization requirements.

PMID- 16977442
TI  - Multi-detector row CT of the head and neck: comparison of different volumes of
      contrast material with and without a saline chaser.
AB  - INTRODUCTION: The aim of this study was to determine the effect of different
      volumes of contrast material with and without a saline chaser on tissue
      enhancement in multidetector row CT (MDCT) of the head and neck. METHODS: In a
      blind prospective fashion, 120 patients were randomized into the following four
      groups: group 1, 80 ml contrast material administered at a flow rate of 2.0 ml/s;
      group 2, 80 ml followed by 40 ml saline at 2.0 ml/s; group 3, 60 ml at 1.5 ml/s;
      and group 4, 60 ml followed by 30 ml saline at 1.5 ml/s. The attenuation values
      of the carotid artery, internal jugular vein, and muscle were measured at an
      interval of 1.5 s in each patient. The degree of perivenous artifacts was
      subjectively assessed. RESULTS: Mean attenuation values in the carotid artery and
      internal jugular vein were significantly higher in groups 1 and 2 than in groups
      3 and 4. The width of the diagnostic window (both carotid and jugular enhancement
      >150 HU) were significantly longer in groups 1 and 2 than in groups 3 and 4. The
      addition of a saline chaser did not result in improved vascular enhancement or a
      wider diagnostic window, but reduced perivenous artifacts, compared with using
      contrast material alone. CONCLUSION: Reduction of contrast material from 80 to 60
      ml results in insufficient enhancement of neck vessels. In addition, the benefit
      of a saline chaser technique is not obvious except for its ability to reduce
      perivenous artifacts.

PMID- 16977443
TI  - Diffusion-weighted MR imaging (DWI) in spinal cord ischemia.
AB  - INTRODUCTION: Spinal cord infarction is a rare clinical diagnosis characterized
      by a sudden onset of paralysis, bowel and bladder dysfunction, and loss of pain
      and temperature perception, with preservation of proprioception and vibration
      sense. Magnetic resonance imaging (MRI) usually demonstrates intramedullary
      hyperintensity on T2-weighted MR images with cord enlargement. However, in
      approximately 45% of patients, MR shows no abnormality. Diffusion-weighted MR
      imaging (DWI) has been widely used for the evaluation of a variety of brain
      disorders, especially for acute stroke. Preliminary data suggest that DWI has the
      potential to be useful in the early detection of spinal infarction. METHODS: We
      performed DWI, using navigated, interleaved, multishot echo planar imaging
      (IEPI), in a series of six patients with a clinical suspicion of acute spinal
      cord ischemia. RESULTS: In all patients, high signal was observed on isotropic
      DWI images with low ADC values (0.23 and 0.86x10(-3) cm(2)/s), indicative of
      restricted diffusion. CONCLUSION: We analyzed the imaging findings from
      conventional MR sequences and diffusion-weighted MR sequences in six patients
      with spinal cord infarction, compared the findings with those in published
      series, and discuss the value of DWI in spinal cord ischemia based on current
      experience. Although the number of patients with described DWI findings totals
      only 23, the results of previously published studies and those of our study
      suggest that DWI has the potential to be a useful and feasible technique for the
      detection of spinal infarction.

PMID- 16977444
TI  - ATX-S10(Na)-PDT shows more potent effect on collagen metabolism of human normal
      and scleroderma dermal fibroblasts than ALA-PDT.
AB  - Recent study revealed that photodynamic therapy (PDT) with a novel
      photosensitizer (ATX-S10(Na)) shows more potent effects for various skin diseases
      than ALA-PDT. The effect of ATX-S10(Na)-PDT on dermal fibroblasts is still
      unknown. Using dermal fibroblasts derived from normal and scleroderma patients,
      and mouse skin in vivo, we compared the effects of ATX-S10(Na)-PDT and ALA-PDT.
      Fibroblasts from normal, scleroderma patients or mice skin were treated with ATX
      S10(Na)-PDT or ALA-PDT. After the PDT treatments, the expression of matrix
      metalloproteinases (MMPs) Tissue inhibitors of metalloproteinases (TIMPs) and
      collagen synthesis was assayed using ELISA and reverse transcription-PCR (RT
      PCR). The expression of MMP-1 and MMP-3 was slightly decreased and collagen I
      mRNA was significantly increased in scleroderma fibroblasts compared with normal
      fibroblasts. Both ATX-S10(Na)-PDT and ALA-PDT increased the expression of MMP-1
      and MMP-3 in protein and mRNA levels in both normal and scleroderma fibroblasts
      with more potent effect by ATX-S10(N)-PDT. Collagen I synthesis was markedly
      decreased by ATX-S10(Na)-PDT and by ALA-PDT again with more potent effect by ATX
      S10(Na)-PDT in both normal and scleroderma fibroblasts. In mice skin the effect
      of PDT for MMPs and collagen I was also detected and the effect was more potent
      in ATX-S10(Na)-PDT. In contrast, MMP-2, TIMP-1, TIMP-2, and collagen III
      expression was not affected by the ATX-S10(Na)-PDT or ALA-PDT treatment. ATX
      S10(Na)-PDT is more potent modulator for dermal matrix components than ALA-PDT
      and might be useful for scleroderma patients.

PMID- 16977445
TI  - The effects of Musk T on peroxisome proliferator-activated receptor [PPAR]-alpha
      activation, epidermal skin homeostasis and dermal hyaluronic acid synthesis.
AB  - Peroxisome proliferators activated receptors (PPARs) are a family of nuclear
      hormone receptors that heterodimer with the retinoid X receptor and function as
      transcriptional regulators of genes. Topically Applied PPAR-alpha agonists
      possess receptor mediated, pro-differentiating/anti-proliferative effects, lipid
      metabolism stimulation, and anti-inflammatory activity, which suggest that they
      could be beneficial for the treatment of a variety of cutaneous diseases.
      Hyaluronan (HA), a high-molecular-weight linear glycosaminoglycan consisting of
      alternating D: -glucuronic acid and N-acetyl-D: -glucosamine residues, is one of
      the major extracellular matrix components in skin. Among the family of HA
      synthase genes (HAS1, 2, 3) so far identified, one group has demonstrated that
      the expressions of HAS2 and HAS3 play crucial roles in the regulation of HA
      synthesis in human skin fibroblasts and keratinocytes, respectively, but the
      precise regulatory mechanisms are still unknown. We examine Musk T called
      Ethylene brassylate, Astratone or 1,4-Dioxacycloheptadecane-5,17-dione, which
      used as just a perfume ingredient, plays a role as PPAR-alpha ligand in vitro and
      stimulates skin barrier recovery, ceramide synthesis, beta-Glucocerebrosidase,
      involucrin expression in epidermis in vivo; and examine that Musk T stimulates
      HAS expression and HA synthesis in human skin fibroblast. Through these
      experiments, we conclude that Musk T is PPAR-alpha ligand, effects on
      keratinocyte differentiation, intercellular lipid synthesis in epidermis, HA
      synthesis stimulation in dermis.

PMID- 16977446
TI  - Disinhibition of upper limb motor area by voluntary contraction of the lower limb
      muscle.
AB  - It is well known that monosynaptic spinal reflexes and motor evoked potentials
      following transcranial magnetic stimulation (TMS) are reinforced during phasic
      and intensive voluntary contraction in the remote segment (remote effect).
      However, the remote effect on the cortical silent period (CSP) is less known. The
      purpose of the present study is to determine to what extent the CSP in the
      intrinsic hand muscle following TMS is modified by voluntary ankle dorsiflexion
      and to elucidate the origin of the modulation of CSP by the remote effect. CSP
      was recorded in the right first dorsal interosseous while subjects performed
      phasic dorsiflexion in the ipsilateral side under self-paced and reaction-time
      conditions. Modulation of the peripherally-induced silent period (PSP) induced by
      electrical stimulation of the ulnar nerve was also investigated under the same
      conditions. In addition, modulation of the CSP was investigated during ischemic
      nerve block of the lower limb and during application of vibration to the tibialis
      anterior tendon. The duration of CSP was significantly shortened by phasic
      dorsiflexion, and the extent of shortening was proportional to dorsiflexion
      force. Shortening of the CSP duration was also observed during tonic
      dorsiflexion. In contrast, the PSP duration following ulnar nerve stimulation was
      not altered during phasic dorsiflexion. Furthermore, the remote effect on the CSP
      duration was seen during ischemic nerve block of the lower limb and the pre
      movement period in the reaction-time paradigm, but shortening of the CSP was not
      observed during tendon vibration. These findings suggest that phasic muscle
      contraction in the remote segment results in a decrease in intracortical
      inhibitory pathways to the corticospinal tract innervating the muscle involved in
      reflex testing and that the remote effect on the CSP is predominantly cortical in
      origin.

PMID- 16977447
TI  - Differential effects of reward and punishment on conscious and unconscious eye
      movements.
AB  - Very little is known about how human movements are influenced by abstract rewards
      and punishments relevant for human behaviour. The purpose of this study was to
      expand our knowledge of the behavioural effects of monetary reward and
      punishment. We introduced a high and low reward and punishment scheme into an
      antisaccade task where trials were either rewarded for a correct response (+1 or
      +25p) or punished for an incorrect response (-1 or -25p). The monetary value of
      the trial was indicated by the go signal, so subjects had to both program the
      location of the movement and determine the valence in the short interval before
      the eye movement was executed. We analysed both correct antisaccade responses and
      prosaccade errors. Importantly, the errors in this task can be either conscious
      (recognised) or unconscious (unrecognised). Saccades in both high-reward and high
      punishment trials were slowed compared to saccades in low-reward and low
      punishment trials, respectively. Therefore, unlike moderate rewards only
      (Blaukopf and DiGirolamo in Exp Brain Res 167:654-659, 2005), combining rewards
      and punishments and increasing motivation levels leads to a delay in movement
      execution during high valence trials where all actions are slowed, even errors.
      However, unconscious errors were differentially affected as they were speeded
      when punishment was high. We conclude that reward and punishment similarly
      influence the programming of conscious movements, but the strong saliency for
      punishment affords unconscious errors immunity from this delay.

PMID- 16977448
TI  - Adaptive changes in postural strategy selection in chronic low back pain.
AB  - Chronic low back pain (CLBP) patients achieve postural stability during
      challenging stance conditions by increasing sway speed. We investigated the
      mechanisms underlying this behavior, and whether postural strategy selection may
      be influenced by short-term experience of postural perturbation. Thirteen CLBP
      patients and thirteen age-matched controls underwent posturography tests.
      Subjects were asked to stand quietly: (a) with eyes open and eyes closed, and (b)
      while expecting a series of four backward translations of the support surface.
      Data from condition (a) was subjected to sway density analysis (SDA). This
      computes the number of consecutive spaces and respectively time samples during
      which center of pressure (COP) displacements remained inside a 2.5 mm radius.
      Three parameters of this analysis were considered: the mean number of peaks (MP),
      reflecting the time spent by COP in regions of stability, the mean time between
      peaks (MT) relating to the rate of production of posturographic commands, and the
      mean spatial distance (MD), reflecting the distance between stable regions. In
      condition (b) the mean COP positions were analyzed during the time (500 ms)
      preceding each translation. The MD was significantly increased in the CLBP group
      as compared to controls (P < 0.01), while the MP and MT did not present any
      significant difference. The expectation of backward translations initially
      produced a different COP positioning between the two groups (P < 0.0001) which
      decreased with repetition of platform translations (controls: PDelta1-4 < 0.002;
      patients: PDelta1-4 < 0.005). The findings show that the timing and the rate of
      the balance motor commands is comparable between the two groups. On the other
      hand, there is greater distance between regions of stability in the patient
      group. Such modification of motor control patterns might be the consequence of a
      reweighting of sensory input, possibly due to a deterioration of its reliability.
      Platform translation findings show that both groups aimed at optimizing their
      posture selection strategy based on prior testing experience. CLBP patients make
      use of a different postural motor strategy to maintain quiet stance. This is
      probably the consequence of an imprecise internal estimate of body sway, due to
      reduced accuracy in the sensory integration process.

PMID- 16977449
TI  - LATER predicts saccade latency distributions in reading.
AB  - When saccades are evoked by suddenly presented visual stimuli, the stochastic
      distribution of their reaction times is typically recinormal, in conformity with
      the LATER model of decision-making, sometimes with an additional sub-population
      of early responses. In the real world, saccades are more often spontaneous
      responses to static features of the visual world; nevertheless, the time between
      the end of one saccade and the start of the next may be regarded as a reaction
      time to the new image that is presented to the retina. The distribution of these
      times is qualitatively similar to that of evoked saccades, but typically with a
      longer median and more of the early responses. Here, we analyse the statistical
      distributions of fixation times from a large database of spontaneous saccades
      made while reading and show that the distributions are altered in characteristic
      ways by particular features of the current fixation: likely familiarity of the
      currently fixated word, and its proximity to the preceding fixation. These
      alterations are of the kind predicted by LATER: familiarity appears to influence
      the mean rate at which the decision signal approaches completion, whereas
      proximity to the previous fixation, presumably because it provides partial prior
      information about the upcoming word, appears to increase prior probability. We
      conclude that spontaneous saccades may be successfully described by the same
      decision-making model that can be used for evoked ones.

PMID- 16977451
TI  - Reconstruction of comminuted posterior wall fractures using the buttress
      technique: a review of 32 fractures.
AB  - Fractures of the posterior wall are the most common of the acetabular fractures.
      The aim of this study was to assess the medium-term results of reconstruction of
      comminuted posterior wall fractures of the acetabulum by using the buttress
      technique. This is a retrospective review conducted at a level 1 trauma centre.
      Thirty-two patients (25 men, 7 women, mean age 41 years, range 14-80 years) with
      comminuted posterior wall fracture of the acetabulum underwent reconstruction of
      the posterior wall during the period of July 1998 to February 2004. The average
      follow-up was 43 months (range 24-70 months). Clinical evaluation was based on
      modified Merle d'Aubigne and Postel scoring. Radiographic evaluation was
      according to criteria developed by Matta. The postoperative reduction was graded
      as anatomical in 28 patients (88%) and imperfect in 4 patients (12%). The
      clinical outcome was excellent in 11 (34% ), very good in 9 (28%), good in 4
      (12%), fair in 3 (9%) and poor in 5 (15%). Radiological grading at the final
      follow-up was excellent 12 (37%), good 11 (34%), fair 4 (12%) and poor 5 (15%).
      Reconstruction of comminuted posterior wall acetabular fractures by buttress
      technique can be expected to produce good results. It can provide a stable
      fixation of the posterior wall amenable to early range of motion and weight
      bearing.

PMID- 16977450
TI  - The influence of current mood on affective startle modulation.
AB  - The affect-modulated startle response is a reliable indicator of the affective
      processing of stimuli. It may be influenced by trait and state affective
      variables as well as psychopathological status. The aim of the present study was
      to determine the influence of the current mood state on startle modulation. Forty
      five healthy volunteers viewed affective stimuli while eye blink responses and
      subjective emotional ratings were assessed. In addition, the current state of
      mood was assessed, pre and post the experimental procedure. Subjects were divided
      into those that were in a more positive and those that were in a more negative
      mood based on a median split. Compared to subjects in a positive mood those in a
      more negative mood showed significantly reduced startle amplitudes after viewing
      the negative and neutral stimuli. The results of the present study show that
      changes in startle responses are not only related to the current state of
      psychopathology but also to the general affective state of the participants
      during the assessments.

PMID- 16977452
TI  - Giant cell tumor of the nasal cavity: case report.
AB  - Soft tissue giant cell tumor of low malignant potential is a rare tumor located
      in superficial and deep soft tissue. Tumors with osteoclast-like giant cells have
      been reported in various sites as breast, salivary glands, lung, kidney and
      pancreas. These tumors are composed of evenly spaced multinucleated giant cells
      in a background of mononuclear component composed of round, oval or spindled
      cells. No atypia or significant mitotic activity is encountered.
      Immunohistochemical stains for TRAP, smooth muscle actin, desmin and cytokeratins
      are of great value for diagnosis. Nasal cavity represents a very unusual location
      for this type of tumors; soft tissue tumors must be included in the differential
      diagnosis of nasal obstruction. Due to the possibility of local recurrence,
      clinical follow-up is recommended.

PMID- 16977453
TI  - The B2 domain of VIVIPAROUS1 is bi-functional and regulates nuclear localization
      and transactivation.
AB  - The transcriptional regulator VIVIPA-ROUS1 (VP1) is composed of four functional
      domains that control different aspects of gene expression during seed
      development. The B2 domain is required for its role as a transcriptional
      activator, functioning at the site of transcription and/or for its transport into
      the nucleus. Previous work showed that the B2 domain was required for
      transactivation of the Em promoter. We demonstrate that VP1::GFP localizes to the
      nucleus of barley (Hordeum vulgare) aleurone cells, but when B2 is deleted,
      nuclear accumulation is lost. However, the B2 domain itself is not sufficient for
      nuclear localization of GFP::GUS. Using point mutagenesis on the putative NLS
      within B2, we show that the VP1::GFP still accumulates in the nucleus. Utilizing
      a comparative approach, through the alignment of B2 domains from various VP1/ABI3
      proteins, oincluding the ABI3 orthologs from Physcomitrella patens, revealed the
      involvement of other conserved amino acids. Mutating VP1 at the conserved
      threonine on the N-terminal side of the putative NLS and at a conserved arginine
      glutamine-arginine sequence on the C-terminal side prevented nuclear localization
      of VP1. A single amino acid change, from alanine to threonine, within this NLS
      found in the Arabidopsis abi3-7 mutant prevents transcription of AtEm1 and AtEm6
      in vivo. We show that this same mutation in VP1 prevents transactivation of the
      Em-GUS reporter in barley aleurone but does not interfere with nuclear
      localization. Our data demonstrate that the B2 domain of VP1 is bifunctional in
      nature regulating both nuclear localization and transactivation.

PMID- 16977454
TI  - Development of the light-harvesting chlorophyll antenna in the green alga
      Chlamydomonas reinhardtii is regulated by the novel Tla1 gene.
AB  - The Chlamydomonas reinhardtii tla1 (truncated light-harvesting chlorophyll
      antenna size) mutant was generated upon DNA insertional mutagenesis and shown to
      specifically possess a smaller than wild type (WT) chlorophyll antenna size in
      both photosystems. Molecular and genetic analysis revealed that the exogenous
      plasmid DNA was inserted at the end of the 5' UTR and just prior to the ATG start
      codon of a hitherto unknown nuclear gene (termed Tla1), which encodes a protein
      of 213 amino acids. The Tla1 gene in the mutant is transcribed with a new 5' UTR
      sequence, derived from the 3' end of the transforming plasmid. This replacement
      of the native 5' UTR and promoter regions resulted in enhanced transcription of
      the tla1 gene in the mutant but inhibition in the translation of the respective
      tla1 mRNA. Transformation of the tla1 mutant with WT Tla1 genomic DNA
      successfully rescued the mutant. These results are evidence that polymorphism in
      the 5' UTR of the Tla1 transcripts resulted in the tla1 phenotype and that
      expression of the Tla1 gene is a prerequisite for the development/assembly of the
      Chl antenna in C. reinhardtii. A blast search with the Tla1 deduced amino acid
      sequence

PMID- 16977455
TI  - Anisocotyly and meristem initiation in an unorthodox plant, Streptocarpus rexii
      (Gesneriaceae).
AB  - In common with most Old World Gesneriaceae; Streptocarpus Lindl. shows
      anisocotylous growth, i.e., the continuous growth of one cotyledon after
      germination. Linked to this phenomenon is an unorthodox behaviour of the shoot
      apical meristem (SAM) that determines the growth pattern of acaulescent species
      (subgenus Streptocarpus). In contrast caulescent species develop a conventional
      central post-embryonic SAM (mainly subgenus Streptocarpella). We used S. rexii
      Lindl. as a model to investigate anisocotyly and meristem initiation in
      Streptocarpus by using histological techniques and analyses of the expression
      pattern of the meristematic marker SrSTM1 during ontogeny. In contrast to
      Arabidopsis thaliana (L.) Heynh., S. rexii does not establish a SAM during
      embryogenesis, and the first evidence of a SAM-like structure occurs during post
      embryonic development on the axis (the petiolode) between the two cotyledons. The
      expression pattern of SrSTM1 suggests a function in maintaining cell division
      activity in the cotyledons before becoming localized in the basal meristem,
      initially at the proximal ends of both cotyledons, later at the base of the
      continuously growing macrocotyledon, and the groove meristem on the petiolode.
      The latter is equivalent to a displaced SAM seemingly originating de novo under
      the influence of endogenous factors. Applied cytokinin retains SrSTM1expression
      in the small cotyledon, thus promoting isocotyly and re-establishment of a
      central post-embryonic SAM. Hormone-dependent delocalization of the process of
      meristem development could underlie anisocotyly and the unorthodox SAM formation
      in Streptocarpus.

PMID- 16977456
TI  - Identification and characterization of genes expressed in early embryogenesis
      from microspores of Brassica napus.
AB  - To understand the mechanism in induction of embryogenesis from microspores of
      Brassica napus, we isolated exhaustively the genes expressed differentially
      during the early stage of microspore culture. A subtracted cDNA library composed
      of up-regulated genes during androgenic initiation was produced by suppression
      subtractive hybridization followed by differential screening by dot blot
      hybridization, and a total of 136 non-redundant expressed sequence tags were
      identified. Analysis of the potential functions of the genes showed that 64% of
      these genes were homologous to known genes, and the remaining ones have not been
      previously reported to participate in embryogenesis. Many embryo-specific genes
      were contained in the isolated genes, for example, genes cording lipid transfer
      protein, napin, cruciferin, oleosin, and phytosulfokine. Real-time RT-PCR
      analysis for 15 selected genes, which are understood to not be related with
      embryogenesis, demonstrated that all genes were expressed highly in the early
      stage of microspore embryogenesis. A few genes also showed higher expression in
      microspores cultured in non-embryogenic condition or in later stages of embryos.
      A principal component analysis based on expression profiles of the 15 genes
      demonstrated that these genes were classified into 2 groups, one characterized by
      their high expression in initiation of embryogenesis, and the other characterized
      by their expression in the early to middle stage of embryogenesis. The
      expressions of these genes were confirmed in zygotic embryos. The identification
      and characterization of the genes isolated in the present study provide novel
      information on microspore embryogenesis in Brassica.

PMID- 16977457
TI  - Evidence for intracellular spatial separation of hexokinases and fructokinases in
      tomato plants.
AB  - Four hexokinase (LeHXK1-4) and four fructokinase (LeFRK1-4) genes were identified
      in tomato plants. Previous GFP fusion studies indicate that the gene product of
      LeHXK3 is associated with the mitochondria while that of LeHXK4 is located within
      plastids. In this study we found that the enzyme encoded by the fructokinase gene
      LeFRK3 is also located within plastids. The presence of LeFrk3 enzyme in plastids
      raises the question of the origin of fructose in these organelles. The other
      three FRKs enzymes, LeFrk1&2&4, are located in the cytosol. Unlike LeFrk1&2&4,
      the two additional HXKs, LeHxk1&2, share a common membrane anchor domain and are
      associated with the mitochondria similar to LeHxk3. The difference in the
      locations of the cytoplasmic FRK and HXK isozymes suggests that glucose
      phosphorylation is confined to defined special intracellular localizations while
      fructose phosphorylation is less confined.

PMID- 16977458
TI  - Increased C-MYC copy numbers on the background of CDKN2A loss is associated with
      improved survival in nodular melanoma.
AB  - PURPOSE: In order to obtain better insight into the genetic background of nodular
      melanoma (NM), we aimed to analyse the frequency of CDKN2A and C-MYC copy number
      changes. The impact of these aberrations on the metastatic potential and
      patient's survival was considered. METHODS: Fluorescent in situ hybridization was
      used to analyse the C-MYC and CDKN2A genes on isolated nuclei from 49 paraffin
      embedded primary NMs. RESULTS: Thirty-six (73.47%) melanoma samples showed CDKN2A
      deletion while 11 of these 36 (22.45%) additionally displayed C-MYC increased
      copy numbers. Cases positive for metastases more commonly displayed CDKN2A
      deletions. However, the combined C-MYC and CDKN2A aberrations were found
      predominantly in the non-metastasizing group of primary NM. The survival analysis
      furthermore demonstrated that patients with combined CDKN2A and C-MYC aberrations
      have a significantly better prognosis than carriers of CDKN2A deletion only.
      CONCLUSIONS: We conclude that the C-MYC increased copy number changes on the
      background of CDKN2A deletions seem to be related to a low metastatic potential
      and better patients' outcome in primary NMs.

PMID- 16977459
TI  - High-density oligonucleotide microarrays and functional network analysis reveal
      extended lung carcinogenesis pathway maps and multiple interacting genes in NNK
      [4-(methylnitrosamino)-1-(3-pyridyle)-1-butanone] induced CD1 mouse lung tumor.
AB  - PURPOSE: NNK [4-(methylnitrosamino)-1-(3-pyridyle)-1-butanone] is a nicotine
      derived nitrosaminoketone contained in tobacco smoke used as a powerful chemical
      carcinogen for rodent experimental models of pulmonary carcinogenesis. To clarify
      its carcinogenetic mechanisms, we examined the expression status of 22,625 mouse
      genes. METHODS: The affymetrix GeneChip mouse expression 430 A arrays have been
      used in CD1-induced mouse lung tumor. The affected genes were analyzed by
      Ingenuity pathway analysis to investigate functional network and gene ontology.
      RESULTS: A total of 876 genes were found to be differentially expressed at least
      twofold between NNK-induced tumors and normal lung tissues, 390 up-regulated and
      486 down-regulated in these lesions. The functions with the highest P values were
      related to cellular growth and proliferation (P = 1.71 x 10(-4) to 4.10 x 10(
      2)). In addition, we identified canonical pathways for Wnt/beta-catenin signaling
      (P = 0.0338). CONCLUSIONS: These results suggest that application of gene
      expression profiling may provide an improved strategy for therapeutic targeting
      of tobacco smoking-induced lung cancer.

PMID- 16977460
TI  - Skipping day 2 antiemetic medications may improve chemotherapy induced delayed
      nausea and vomiting control: results of two pilot phase II trials.
AB  - BACKGROUND: 5HT-3 antagonists and corticosteroids control less than 50% of
      delayed chemotherapy induced nausea and vomiting (CINV) episodes. MATERIALS AND
      METHODS: Two pilot phase II studies were conducted at our institution in which
      all patients received ondansetron 16 mg and dexamethasone 20 mg before highly and
      moderately emetogenic chemotherapy on day 1. Patients on study 1 received
      metoclopramide 10 mg PO q8 h, granisetron 0.5 mg PO QD and dexamethasone 8 mg QD
      on days 2 and 3, whereas only metoclopramide was continued on the same schedule
      on day 4. On study 2, patients received the same medications, but no drugs were
      given on day 2, and the same treatment schedule was given to them but from days 3
      to 5 instead. Patients were interviewed on days 1 and 6. RESULTS: Twenty-one
      patients participated on each study. There were no significant clinical
      differences between these two studied populations. Complete CINV control occurred
      from days 2 to 5 in 23.1% (95% CI: 8 to 47%) on study 1 vs 61.9% (95% CI: 38 to
      81%) of the patients on study 2. By logistic regression, complete CINV control
      was correlated significantly with antiemetic treatment group (p=0.011) even when
      we considered only patients who achieved complete CINV control during the first
      24 h (p=0.031). CONCLUSIONS: Skipping day 2 antiemetic medications does not seem
      to worsen delayed CINV control and may even improve it, perhaps by avoiding
      tachyphylaxis to these medications. A randomized controlled study is in progress
      to confirm these results.

PMID- 16977461
TI  - The effect of irradiance, vertical mixing and temperature on spring phytoplankton
      dynamics under climate change: long-term observations and model analysis.
AB  - Spring algal development in deep temperate lakes is thought to be strongly
      influenced by surface irradiance, vertical mixing and temperature, all of which
      are expected to be altered by climate change. Based on long-term data from Lake
      Constance, we investigated the individual and combined effects of these variables
      on algal dynamics using descriptive statistics, multiple regression models and a
      process-oriented dynamic simulation model. The latter considered edible and less
      edible algae and was forced by observed or anticipated irradiance, temperature
      and vertical mixing intensity. Unexpectedly, irradiance often dominated algal net
      growth rather than vertical mixing for the following reason: algal dynamics
      depended on algal net losses from the euphotic layer to larger depth due to
      vertical mixing. These losses strongly depended on the vertical algal gradient
      which, in turn, was determined by the mixing intensity during the previous days,
      thereby introducing a memory effect. This observation implied that during intense
      mixing that had already reduced the vertical algal gradient, net losses due to
      mixing were small. Consequently, even in deep Lake Constance, the reduction in
      primary production due to low light was often more influential than the net
      losses due to mixing. In the regression model, the dynamics of small, fast
      growing algae was best explained by vertical mixing intensity and global
      irradiance, whereas those of larger algae were best explained by their biomass 1
      week earlier. The simulation model additionally revealed that even in late winter
      grazing may represent an important loss factor during calm periods when losses
      due to mixing are small. The importance of losses by mixing and grazing changed
      rapidly as it depended on the variable mixing intensity. Higher temperature,
      lower global irradiance and enhanced mixing generated lower algal biomass and
      primary production in the dynamic simulation model. This suggests that potential
      consequences of climate change may partly counteract each other.

PMID- 16977462
TI  - Hydrogen isotopic compositions of n-alkanes from terrestrial plants correlate
      with their ecological life forms.
AB  - Stable hydrogen isotopic compositions (deltaD) of compound-specific biomarkers,
      such as n-alkanes from plant leaf waxes, can be used as a proxy for paleoclimatic
      change. However, the relationship between hydrogen isotopes of plant leaf wax and
      plant ecological life forms is not well understood. Here, we report the deltaD of
      n-alkanes from 34 modern terrestrial plants, including twenty-one C(3) plants and
      thirteen C(4) plants from northwestern China, determined using gas
      chromatography/thermal conversion/isotope ratio mass spectrometry. Our data show
      that the stable hydrogen isotopes are poorly correlated with the plant
      photosynthetic pathway (C(3) vs. C(4)) and that they do not give clear regional
      precipitation signals. Together with a comparative analysis of published deltaD
      values from plant leaf waxes in other regions, we believe that the stable
      hydrogen isotope of plant leaf waxes is more closely related to ecological life
      forms of these terrestrial plants (i.e. tree, shrub, and grass). In general, the
      grasses have more negative deltaD values than the co-occurring trees and shrubs.
      Our findings suggest that the deltaD values of sedimentary leaf waxes from higher
      plants may record changes of a plant ecosystem under the influence of
      environmental alteration and imply that reconstruction of the paleoclimate using
      deltaD values from plant n-alkanes should be based upon specific plant taxa, and
      comparison should be made among plants with similar ecological life forms.

PMID- 16977463
TI  - Cathepsin G: the significance in rheumatoid arthritis as a monocyte
      chemoattractant.
AB  - Human cathepsin G (EC 3.4.21.20) has been reported to have the in vitro
      chemotactic activity for human monocytes. In this study, we examined the role of
      cathepsin G in monocyte involvement in joint inflammation of rheumatoid arthritis
      (RA) as a monocyte chemoattractant. Eighteen patients with RA and four patients
      with osteoarthritis (OA) were used in this study. Thiobenzylester substrate, Succ
      Phe-Leu-Phe-S-Bzl, was used to measure the activity of cathepsin G in synovial
      fluids. Monocyte migration induced by cathepsin G and synovial fluids was
      assessed by a 48-well microchemotaxis chamber technique. Immunohistochemical
      staining was performed to determine the cellular origin of cathepsin G in RA
      synovial tissue. A very low activity of cathepsin G was detected in synovial
      fluids from patients with OA. On the other hand, significantly increased activity
      of cathepsin G was detected in patients with RA when compared with the value of
      OA patients. A considerable monocyte chemotactic activity was detected in the
      synovial fluid of RA patients, and the activity was partially decreased by the
      treatment with inhibitors for cathepsin G, alpha1-antichymotrypsin and
      phenylmethylsulfonyl fluoride. The activity of cathepsin G was significantly
      correlated with the neutrophil counts in synovial fluids and the concentration of
      interleukin-6. Immunohistochemical studies showed that cathepsin G was strongly
      expressed by synovial lining cells, and weakly expressed by macrophages and
      neutrophils in synovial tissues. This study indicates that the monocyte
      chemotactic activity of cathepsin G may have a role in the pathogenesis of RA
      synovial inflammation.

PMID- 16977464
TI  - Immobilization of bacteria in silica matrices using citric acid in the sol-gel
      process.
AB  - The aim of this work was to use citric acid in the sol-gel process to generate an
      inorganic polymer that allows bacterial survival for long periods of time and to
      study the influence of different storage temperatures. We compared gram-negative
      Escherichia coli and gram-positive Staphylococcus aureus, immobilized and
      preserved at different storage temperatures in silica matrices prepared by the
      method proposed. Immobilized E. coli and S. aureus in silica matrices were stored
      in sealed tubes at 20, 4, -20, and -70 degrees C for 4 months during which the
      number of viable cells was analyzed. Results show that the immobilization in
      silica matrices using citric acid, to neutralize the alkalinity of the silica
      precursors, makes the technique not only biocompatible but also easier to perform
      since polymerization does not occur immediately as it does when hydrochloric acid
      is utilized.

PMID- 16977465
TI  - A gene linB2 responsible for the conversion of beta-HCH and 2,3,4,5,6
      pentachlorocyclohexanol in Sphingomonas sp. BHC-A.
AB  - Commercial formulations of hexachlorocyclohexane (HCH) consist of a mixture of
      four isomers: alpha, beta, gamma, and delta. All four isomers are toxic and
      recalcitrant pollutants. beta-HCH is more problematic due to its longer
      persistence in the environment. Sphingomonas sp. BHC-A was able to degrade not
      only alpha-, gamma-, and delta-HCH but also beta-HCH. To clone a gene responsible
      for the degradation of beta-HCH, a Tn5 mutation was introduced into BHC-A, and
      one mutant BHC-A45 defective in beta-HCH degradation was selected. Sequencing
      analysis showed this mutant had a Tn5 insertion at the site of one haloalkane
      dehalogenase gene, designated linB2. linB2 was overexpressed in Escherichia coli
      and the 32-kDa product LinB2 showed the conversion activity of not only beta-HCH
      to beta-2,3,4,5,6-pentachlorocyclohexanol (beta-PCHL) but also beta-PCHL to beta
      2,3,5,6-tetrachloro-1,4-cyclohexanediol.

PMID- 16977466
TI  - High activity of xylose reductase and xylitol dehydrogenase improves xylose
      fermentation by recombinant Saccharomyces cerevisiae.
AB  - Xylose fermentation performance was studied of a previously developed
      Saccharomyces cerevisiae strain TMB 3057, carrying high xylose reductase (XR) and
      xylitol dehydrogenase (XDH) activity, overexpressed non-oxidative pentose
      phosphate pathway (PPP) and deletion of the aldose reductase gene GRE3. The
      fermentation performance of TMB 3057 was significantly improved by increased
      ethanol production and reduced xylitol formation compared with the reference
      strain TMB 3001. The effects of the individual genetic modifications on xylose
      fermentation were investigated by comparing five isogenic strains with single or
      combined modifications. All strains with high activity of both XR and XDH had
      increased ethanol yields and significantly decreased xylitol yields. The presence
      of glucose further reduced xylitol formation in all studied strains. High
      activity of the non-oxidative PPP improved the xylose consumption rate. The
      results indicate that ethanolic xylose fermentation by recombinant S. cerevisiae
      expressing XR and XDH is governed by the efficiency by which xylose is introduced
      in the central metabolism.

PMID- 16977467
TI  - Determination of soluble and granular inorganic polyphosphate in Corynebacterium
      glutamicum.
AB  - Corynebacterium glutamicum forms inorganic polyphosphate (poly P) that may occur
      as soluble (cytosolic) poly P and/or as volutin granules. A suitable method for
      monitoring soluble and granular poly P in C. glutamicum was developed and applied
      to C. glutamicum cells cultivated under different growth conditions. Under
      phosphate-limiting conditions, C. glutamicum did not accumulate poly P, but it
      rebuilt its poly P storages when phosphate became available. The poly P content
      of C. glutamicum growing on glucose minimal medium with sufficient phosphate
      varied considerably during growth. While the poly P content was minimal in the
      midexponential growth phase, two maxima were observed in the early exponential
      growth phase and at entry into the stationary growth phase. Cells in the early
      exponential growth phase primarily contained granular poly P, while cells
      entering the stationary growth phase contained soluble, cytosolic poly P. These
      results and those obtained for C. glutamicum cells cultivated under hypo- or
      hyperosmotic conditions or during glutamate production revealed that the poly P
      content of C. glutamicum and the partitioning between cytosolic and granular
      forms of poly P are dynamics and depend on the growth conditions.

PMID- 16977468
TI  - Bioaugmenting anaerobic digestion of biosolids with selected strains of Bacillus,
      Pseudomonas, and Actinomycetes species for increased methanogenesis and odor
      control.
AB  - The objective of this study was to evaluate the effects of bioaugmenting
      anaerobic biosolids digestion with a commercial product containing selected
      strains of bacteria from genera Bacillus, Pseudomonas, and Actinomycetes, along
      with ancillary organic compounds containing various micronutrients. Specifically,
      the effects of the bioaugment in terms of volatile solids destruction and
      generation and fate of odor-causing compounds during anaerobic digestion and
      during storage of the digested biosolids were studied. Two bench-scale anaerobic
      digesters receiving primary and secondary clarifier biosolids from various full
      scale biological wastewater treatment plants were operated. One of the digesters
      received the bioaugment developed by Organica Biotech, while the other was
      operated as control. The bioaugmented digester generated 29% more net CH(4)
      during the 8 weeks of operation. In addition, the average residual propionic acid
      concentration in the bioaugmented digester was 54% of that in the control. The
      monitoring of two organic sulfide compounds, methyl mercaptan (CH(3)SH) and
      dimethyl sulfide (CH(3)SCH(3)), clearly demonstrated the beneficial effects of
      the bioaugmentation in terms of odor control. The biosolids digested in the
      bioaugmented digester generated a negligible amount of CH(3)SH during 10 days of
      post-digestion storage, while CH(3)SH concentration in the control reached nearly
      300 ppm(v) during the same period. Similarly, peak CH(3)SCH(3) generated by
      stored biosolids from the bioaugmented digester was only 37% of that from the
      control.

PMID- 16977469
TI  - Production of hydrolysate with antioxidative activity by enzymatic hydrolysis of
      extruded corn gluten.
AB  - Hydrolysate of extruded corn gluten with higher solubility and antioxidative
      property was prepared. Extrusion and starch removal of corn gluten were applied
      as pretreatment before enzymatic hydrolysis by Alcalase. The amylase hydrolysis
      of starch at 70 degrees C for 3 h resulted in the removal of the starch from the
      extruded corn gluten. The best hydrolysis results can be obtained by conducting
      the hydrolysis at 60 degrees C with water addition 20 g/g protein, enzyme
      addition 0.048 Ansen units/g protein, pH 8.5, and 120 min. Degree of hydrolysis
      of extruded and nonextruded corn gluten reached 39.54 and 31.16%, respectively,
      under the optimal condition. Sodium dodecyl sulfate polyacrylamide gel
      electrophoresis of the optimal hydrolysate revealed that proteolysis of extruded
      corn gluten was more extensive than proteolysis of its counterpart which was not
      subjected to extrusion. The molecular weight of the peptides in the optimal
      hydrolysate was mainly over 3,710-660 Da as determined by gel filtration
      chromatography. The hydrolysates displayed good solubility and antioxidative
      activity. The separation profile of the hydrolysate on an ion exchange
      chromatography of Q-Sepharose Fast Flow showed that many kinds of peptides had
      antioxidative effect. A new peptide with antioxidative activity was purified, and
      its amino acid sequence was Phe-Pro-Leu-Glu-Met-Met-Pro-Phe, which was identified
      by Q-TOF2 mass spectrometry.

PMID- 16977470
TI  - Expression and characterization of a thermostable sarcosine oxidase (SOX) from
      Bacillus sp. in Escherichia coli.
AB  - A heat-stable sarcosine oxidase produced by Bacillus sp. BSD-8 (SOX) had been
      studied and its complete gene sequence, which contained 1,164 bp nucleotides and
      encoded a protein of 387 amino acids, was obtained by DNA Walking method. The sox
      gene was cloned and functionally overexpressed in E. coli and the recombinant SOX
      (rSOX) was purified to homogeneity, its properties was studied and compared with
      the wild type of SOX. The rSOX as well as SOX was stable at 60 degrees C and at
      pH 7.0 approximately 10.0, respectively. The optimal temperature for this enzyme
      was 60 degrees C and at pH 8.5, it showed its highest activity. The Km and Kcat
      of the enzyme was 3.1 mM and 20.3/s, respectively. The difference between the
      properties of the SOX and rSOX was that the SOX contained noncovalent FAD,
      whereas the rSOX contained covalent FAD. The study also showed that an increased
      number of alanine residues in the rSOX might have some contribution in the
      enzymatic thermostability.

PMID- 16977471
TI  - Case report: Corticosteroid-resistant nephrotic syndrome: treatment with
      rapamune.

PMID- 16977472
TI  - End-stage renal disease as the presenting manifestation of renal systemic lupus
      erythematosus.
AB  - About one-half of all children with systemic lupus erythematosus have clinical
      evidence of renal disease at initial presentation, such as proteinuria and acute
      renal failure. Herein, we report a case of a teenager who presented with end
      stage renal disease (ESRD) of uncertain etiology, and who was subsequently
      determined to have lupus. The purpose of this report is to make health-care
      professionals aware of this unusual presentation of renal lupus, which has never
      been reported before. Children presenting in ESRD should be worked-up for
      autoimmune diseases since the discovery of such a disease process may impact
      future decision-making, especially with respect to subsequent renal
      transplantation.

PMID- 16977473
TI  - Renal anomalies in family members of infants with bilateral renal
      agenesis/adysplasia.
AB  - Renal agenesis/adysplasia is the leading etiology of end stage renal disease in
      children. The etiology for renal agenesis/adysplasia has not been identified. The
      purpose of the present study was to determine if renal agenesis/adysplasia occur
      in a familial pattern. Twenty seven cases of bilateral renal agenesis/adysplasia
      were identified by review of autopsy records, and four were excluded. A male
      excess of 2.8:1 was noted with a mean gestation of 35 weeks. Prenatal and family
      histories were obtained on 11/23 families. Potential embryologic stressors were
      identified in 8/11 pregnancies. Thirty-four 1st and 2nd degree relatives from
      five families participated in a renal ultrasound exam. An increased prevalence of
      congenital renal anomalies was identified in the relatives of index patients with
      bilateral renal agenesis/adysplasia (14.7%) compared to controls (2.2%), with a
      recurrence risk of 6.2 for 1st degree relatives. The most frequently identified
      renal anomalies in the family members were solitary kidneys and duplicated
      collecting systems. The increased prevalence of a range of renal anomalies within
      affected families raises the possibility that isolated renal malformations result
      from unidentified gene-environment interactions.

PMID- 16977474
TI  - Bone mineral density in children with chronic renal failure.
AB  - Bone mineral density (BMD) is important in children and adolescents because of
      its relationship to long-term skeletal health, and because, in adults with
      chronic renal failure (CRF), a relationship between low BMD and vascular
      calcification has been suggested. To investigate the relationship between BMD and
      manipulable factors that might affect it, i.e. plasma calcium, phosphate and
      parathyroid hormone (PTH), 64 patients with a median glomerular filtration rate
      (GFR) of 31 (range 7-60) ml min(-1) 1.73 m(-2) and median age of 10.0 (4.1-16.9)
      years were followed over 1.3 (0.7-1.7) years at an average of 5 (3-14) clinic
      visits. At one visit, BMD of the lumbar spine was measured by dual energy X-ray
      absorptiometry. The mean BMD Z-score was normal (=0.0). Overall mean calcium,
      phosphate and PTH levels were in their respective normal ranges. The majority of
      the patients (72%) were treated with calcium carbonate, mean dose 65 mg kg(-1)
      day(-1); prescription was positively related to serum calcium levels and calcium
      phosphate product (P=0.012 and P<0.01 respectively). Almost all patients (98%)
      were treated with alfacalcidol, mean dose 12 ng kg(-1) day(-1); prescription was
      not related to investigated factors. Patients grew well; there was no change in
      height standard deviation score (DeltaHtSDS=0.0). Normal BMD Z-score for age and
      sex can be achieved in children with CRF managed with the aim of maintaining
      normal PTH levels by dietary phosphate restriction, calcium-based phosphate
      binders and small doses of alfacalcidol. Further investigation of the underlying
      bone by the use of biopsy and histomorphometry is required to determine actual
      bone health.

PMID- 16977476
TI  - A role for mesencephalic dopamine in activation: commentary on Berridge (2006).

PMID- 16977475
TI  - Assessment of cognitive function in the heterozygous reeler mouse.
AB  - RATIONALE: The heterozygous reeler mouse has been proposed as a genetic mouse
      model of schizophrenia based on several neuroanatomical and behavioral
      similarities between these mice and patients with schizophrenia. However, the
      effect of reelin haploinsufficiency on one of the cardinal symptoms of
      schizophrenia, the impairment of prefrontal-cortex-dependent cognitive function,
      has yet to be determined. OBJECTIVE: Here, we investigated multiple aspects of
      cognitive function in heterozygous reeler mice that are known to be impaired in
      schizophrenic patients. METHODS: Heterozygous reeler mice were assessed for (1)
      cognitive flexibility in an instrumental reversal learning task, (2) impulsivity
      in an inhibitory control task, (3) attentional function in a three-choice serial
      reaction time task, and (4) working memory in a delayed matching-to-position
      task. RESULTS: No differences were found between heterozygous reeler mice and
      wild-type littermate controls in any prefrontal-related cognitive measures.
      However, heterozygous reeler mice showed deficits in the acquisition of two
      operant tasks, consistent with a role for reelin in certain forms of learning.
      CONCLUSIONS: These findings suggest that heterozygous reeler mice may not be an
      appropriate model for the core prefrontal-dependent cognitive deficits observed
      in schizophrenia, but may model more general learning deficits that are
      associated with many psychiatric disorders.

PMID- 16977477
TI  - Transdermal nicotine attenuates depression symptoms in nonsmokers: a double
      blind, placebo-controlled trial.
AB  - RATIONALE: Despite established links between nicotine dependence and depression,
      little research has examined the effects of nicotine on depression symptoms.
      OBJECTIVE: This study evaluated the acute and chronic effects of transdermal
      nicotine in nonsmokers with baseline depression symptoms during a 4-week, double
      blind, placebo-controlled trial. METHODS: Nonsmokers with scores >or=10 on the
      Center for Epidemiological Studies Depression scale (CES-D) were recruited from
      the community. Mood and cognitive performance were measured at baseline (day 0)
      and at 1, 8, 21, and 28 days. Participants were randomly assigned to wear a
      placebo or nicotine patch for 4 weeks (3.5 mg/day during weeks 1 and 4; 7 mg/day
      during weeks 2 and 3). The final sample consisted of 11 nonsmokers with a mean
      baseline CES-D score of 27.36 (SD=10.53). RESULTS: Salivary nicotine levels
      indicated the majority of participants were compliant with treatment. Acute
      nicotine did not alter mood. After adjusting for baseline values, chronic
      nicotine resulted in a significant decline in CES-D scores at day 8 (3.5 mg/day),
      but returned to placebo levels by the last visit. This return to baseline levels
      was coincident with a decrease in nicotine administration from 7 to 3.5 mg/day. A
      similar trend for improved response inhibition as measured by the Conners
      Continuous Performance Task was also observed. Reported side effects were
      infrequent and minimal. CONCLUSION: These findings suggest a role for nicotinic
      receptor systems in the pathophysiology of depression and that nicotinic
      compounds should be evaluated for treating depression symptoms.

PMID- 16977478
TI  - The development of migrating muscle precursor cells.
AB  - A major subclass of hypaxial muscle groups is derived from long-range migrating
      precursor cells that delaminate from the dermomyotome. Migrating precursors are
      generated on particular axial levels only, i.e. occipitally, cervically, and on
      the levels of the fore and hind limbs. They express the homeobox gene Lbx1, which
      provides a useful marker for their visualization. In the mouse, migrating
      precursor cells give rise to muscles of the extremities, the hypoglossal chord,
      and the diaphragm. We discuss here the development of this migrating lineage,
      which critically depends on the correct specification of the precursors in the
      dermomyotome, their delamination and correct migration. Finally, proliferation at
      the targets is essential to ensure a correct size of the precursor pool and of
      the muscle that derives thereof.

PMID- 16977479
TI  - Myogenin (Myf4) upregulation in trans-differentiating fibroblasts from a
      congenital myopathy with arrest of myogenesis and defects of myotube formation.
AB  - Congenital myopathies often have an unclear aetiology. Here, we studied a novel
      case of a severe congenital myopathy with a failure of myotube formation.
      Polymerase chain reaction-based analysis was performed to characterize the
      expression patterns of the Desmin, p21, p57, and muscle regulatory factors (MRFs)
      MyoD, Myf4, Myf5 and Myf6 in differentiating skeletal muscle cells (SkMCs),
      normal human fibroblasts and patient-derived fibroblasts during trans
      differentiation. The temporal and spatial pattern of MRFs was further
      characterized by immunocyto- and immunohistochemical stainings. In
      differentiating SkMCs, each MRF showed a characteristic expression pattern.
      Normal trans-differentiating fibroblasts formed myotubes and expressed all of the
      MRFs, which were detected. Interestingly, the patient's fibroblasts also showed
      some fusion events during trans-differentiation with a comparable expression
      profile for the MRFs, particularly, with increased expression of Myf4 and p21.
      Immunohistochemical analysis of normal and patient-derived skeletal musculature
      revealed that Myf4, which is downregulated during normal fetal development, was
      still present in patient-derived skeletal head muscle, which was also positive
      for Desmin and sarcomeric actin. The abnormal upregulation of Myf4 and p21 in the
      patient who suffered from a severe congenital myopathy suggests that the
      regulation of Myf4 and p21 gene expression during myogenesis might be of interest
      for further studies.

PMID- 16977480
TI  - Genomic and non-genomic effects of aldosterone on the individual variation of the
      sweat Na+ concentration during exercise in trained athletes.
AB  - To clarify whether the resting background effects (genomic) or exercise-related
      action (non-genomic) of aldosterone (ALD) is primarily affected to an individual
      variation in the sweat Na+ concentration ([Na+]sweat), we analyzed the cross
      sectional relationship between [Na+]sweat and the plasma ALD concentration during
      rest and exercise in a hot environment. Eleven college-aged male subjects with a
      mean maximal oxygen uptake of 48 (range 42-59) ml kg-1 min-1 performed three
      sessions of 20-min cycle exercise at two levels of intensity (40 or 60% VO2max)
      in a room maintained at 31 degrees C. The chest sweat rate (SRch) and its
      containing Na+ were higher and individual differences in SRch and [Na+]sweat were
      greater at 60% exercise than at 40% exercise. In each individual, the [Na+]sweat
      increased significantly (P<0.05) with the increase in the SRch. In all subjects,
      the mean [Na+]sweat during exercise correlated negatively with the resting plasma
      ALD level at either percentage, but it did not correlate with the exercising ALD.
      These results suggest that individual variations in the increase of the
      [Na+]sweat in response to a rise in the SRch may thus be more closely related to
      the resting ALD than to the exercising ALD. As a result, the genomic action of
      ALD may be affected more by the sweat Na+ variation than by the rapidly non
      genomic action during exercise in humans.

PMID- 16977481
TI  - Validation of the SAPS 3 admission prognostic model in patients with cancer in
      need of intensive care.
AB  - OBJECTIVES: To validate the SAPS 3 admission prognostic model in patients with
      cancer admitted to the intensive care unit (ICU). DESIGN: Cohort study. SETTING:
      Ten-bed medical-surgical oncologic ICU. PATIENTS AND PARTICIPANTS: Nine hundred
      and fifty-two consecutive patients admitted over a 3-year period. INTERVENTIONS:
      None. MEASUREMENTS AND RESULTS: Data were prospectively collected at admission of
      ICU. SAPS II and SAPS 3 scores with respective estimated mortality rates were
      calculated. Discrimination was assessed by area under receiver operating
      characteristic (AUROC) curves and calibration by Hosmer-Lemeshow goodness-of-fit
      test. The mean age was 58.3+/-23.1 years; there were 471 (49%) scheduled
      surgical, 348 (37%) medical and 133 (14%) emergency surgical patients. ICU and
      hospital mortality rates were 24.6% and 33.5%, respectively. The mean SAPS 3 and
      SAPS II scores were 52.3+/-18.5 points and 35.3+/-20.7 points, respectively. All
      prognostic models showed excellent discrimination (AUROC>or=0.8). The calibration
      of SAPS II was poor (p<0.001). However, the calibration of standard SAPS 3 and
      its customized equation for Central and South American (CSA) countries were
      appropriate (p>0.05). SAPS II and standard SAPS 3 prognostic models tended
      somewhat to underestimate the observed mortality (SMR>1). However, when the
      customized equation was used, the estimated mortality was closer to the observed
      mortality [SMR=0.95 (95% CI=0.84-1.07)]. Similar results were observed when
      scheduled surgical patients were excluded. CONCLUSIONS: The SAPS 3 admission
      prognostic model at ICU admission, in particular its customized equation for CSA,
      was accurate in our cohort of critically ill patients with cancer.

PMID- 16977482
TI  - Epidemiology and peculiarities of pediatric multiple organ dysfunction syndrome
      in New Delhi, India.
AB  - OBJECTIVE: Most pediatric studies on multiple organ dysfunction syndrome derive
      from developed countries. There is little information regarding the etiologies
      and outcomes of multiple organ dysfunction syndrome in critically ill children
      from developing countries. The objective of this study was to examine the
      differences in epidemiology of multiple organ dysfunction syndrome and the
      relationship of the Organ Failure Index (OFI) to outcomes from multiple organ
      dysfunction syndrome in critically ill children from a developing country.
      DESIGN: Prospective observational study. SETTING: A 10-bed tertiary pediatric
      intensive care unit. PATIENTS: A total of 1722 children (1 month to 16 years of
      age) admitted to a pediatric intensive care unit during the study period from
      January 1998 to June 2003. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of
      all the patients admitted to the pediatric intensive care unit, 184 patients
      (10.6%) had persistent multiple organ dysfunction syndrome. During the study
      period 136 deaths (7.9%) occurred in the ICU. Multiple organ dysfunction syndrome
      was associated with nearly half of these deaths, 67/136 (49.2%). Overall survival
      of all patients with persistent multiple organ dysfunction syndrome was 64%
      (117/184). In addition to sepsis, falciparum malaria, fulminant hepatic failure,
      dengue shock syndrome, severe poisonings, post cardiopulmonary bypass, and post
      cardiac arrest were significant antecedents of multiple organ dysfunction
      syndrome . Patients with OFI scores of 2, 3, 4-5, and >5 exhibited mortalities of
      9%, 29%, 58%, and 100% respectively. CONCLUSIONS: In addition to "traditional"
      sepsis, common etiologies of multiple organ dysfunction syndrome included
      falciparum malaria, fulminant hepatic failure, and dengue shock syndrome. In
      developing countries like India, multiple organ dysfunction syndrome carries a
      significant risk of mortality which is directly related to the OFI.

PMID- 16977483
TI  - Hyperbaric oxygen therapy prevents coagulation disorders in an experimental model
      of multiple organ failure syndrome.
AB  - OBJECTIVE: To evaluate the effects of hyperbaric oxygen (HBO) therapy on the
      coagulation cascade using an experimental model of multiple organ failure
      syndrome (MOFS). DESIGN: MOFS was induced by zymosan (500mg/kg i.p.) in rats. HBO
      therapy (2ATA) was administered in a cylindrical steel chamber 4 and 11h after
      zymosan administration. In a separate set of experiments animals were monitored
      for 72h, and systemic toxicity was scored. INTERVENTION: Eighteen hours after
      zymosan administration, rats were killed and blood samples were used for analysis
      of hemocoagulative parameters, hemodynamics, and arterial blood gas. MAIN
      RESULTS: Zymosan administration caused MOFS by affecting the coagulation cascade,
      as shown by a significant increase in plasma levels of fibrinogen, tissue
      plasminogen activator, inhibitor of tissue plasminogen activator of type 1, and
      plasma levels of fibrin degradation products vs. control rats. Zymosan-induced
      MOFS was also characterized by a significant increase in von Willebrand antigen
      plasma levels vs. controls. Moreover, zymosan administration induced a
      significant fall in mean arterial blood pressure and alteration in blood gas
      values. HBO therapy significantly reduced the derangements of coagulation
      cascade, the fall in mean blood pressure and alteration in blood gas induced by
      zymosan administration. CONCLUSIONS: The hypercoagulability induced by zymosan
      could be responsible for organ failure and death. Our data demonstrate that HBO
      therapy significantly prevents the alteration in the coagulation cascade and
      arterial blood gas in an experimental model of MOFS.

PMID- 16977484
TI  - Midazolam for refractory status epilepticus in children: higher dosing and more
      rapid and effective control.

PMID- 16977485
TI  - High-dose midazolam therapy for refractory status epilepticus in children.
AB  - OBJECTIVE: To assess the efficacy of high-dose midazolam in the treatment of
      refractory status epilepticus in children. SETTING: Paediatric intensive care
      unit (PICU). DESIGN: Audit of clinical experience. SUBJECTS: Seventeen
      consecutive patients treated for episodes of refractory status epilepticus.
      INTERVENTIONS: Algorithm-driven administration of intravenous midazolam to
      control RSE. Regular, mandatory, patient evaluation to avoid delay in the
      appropriate escalation of therapy. Our target was the abolition of clinical
      seizures within 30 min of initiating treatment and early confirmation of
      cessation of all seizure activity using EEG. The algorithm had failed if clinical
      seizures persisted beyond 30 min despite the administration of midazolam at 24
      microg/kg/min or if administration of a further acute anti-epileptic drug was
      required to achieve seizure control. MEASUREMENTS: The midazolam infusion rate,
      cumulative midazolam dose and duration of midazolam therapy at time of clinical
      seizure control were recorded. Haemodynamic parameters were recorded
      continuously. Episodes of algorithm failure, breakthrough seizures and seizure
      relapses were identified. Patient outcome was measured in terms of survival to
      PICU discharge. RESULTS: In 13 patients (76%) midazolam achieved clinical seizure
      control within 30 min of treatment initiation. Midazolam was eventually
      successful in treating 15 seizure episodes (88%). Breakthrough seizures occurred
      in 8 patients (47%). Relapse after discontinuation of therapy occurred in 1
      patient (6%). No significant adverse effects attributable to the use of midazolam
      occurred. There were 3 deaths (18%) related to underlying CNS pathology.
      CONCLUSIONS: Midazolam can offer control of refractory status epilepticus without
      significant morbidity.

PMID- 16977486
TI  - Conservative treatment of spontaneous spinal epidural hematoma associated with
      oral anticoagulant therapy in a child.
AB  - OBJECTIVE: Spontaneous spinal epidural hematoma (SSEH) is rare in the pediatric
      population. This case report reviews the indications and strategies for
      nonoperative management in selected patients. METHODS: An eight-year-old boy
      presented with back pain. There was no antecedent trauma, but the patient was
      anticoagulated for a mechanical heart valve. MRI revealed an epidural mass from
      T12 to L2 consistent with SSEH. The absence of focal neurologic deficits,
      combined with the high stroke risk with anticoagulation reversal, prompted a
      nonoperative approach. Clinical symptoms resolved over several weeks while
      maintaining therapeutic anticoagulation. Follow-up MRI demonstrated resolution of
      the hematoma. CONCLUSION: SSEH can present in the setting of poorly controlled
      therapeutic anticoagulation in the pediatric population. This case supports the
      premise that patients who present with SSEH without focal neurologic deficit can
      be successfully managed while maintaining therapeutic levels of anticoagulation.
      Close follow-up with frequent neurologic examinations, imaging and monitoring of
      the prothrombin time is mandatory.

PMID- 16977487
TI  - Radiation-induced brain tumours in nevoid basal cell carcinoma syndrome:
      implications for treatment and surveillance.
AB  - INTRODUCTION: We report two cases of radiation-induced intracranial tumours after
      treatment for medulloblastoma presenting in children with nevoid basal cell
      carcinoma syndrome. DISCUSSION: These cases illustrate the need for judicious use
      of post-operative radiotherapy as secondary tumors are commonly reported. This is
      particularly important as the initial tumour in this cohort is of the 'less
      aggressive' desmoplastic subtype.

PMID- 16977488
TI  - Influence of freezing and low molecular weight cryoprotectants on microsomal
      membrane structure: a study by multiparametric fluorescent probe.
AB  - The influence of low molecular weight cryoprotectants (CPs) such as glycerol
      (GL), 1,2-propanediol (PD) and dimethylsulfoxide (DMSO) on the structure of rat
      liver microsomal membranes on the stages of equilibration and upon freezing up to
      -196 degrees C was studied using a multiparametric fluorescent probe of flavonol
      nature. It was estimated that the studied CPs have individual concentration
      ranges defining low amplitude of their action on biomembranes. An exceeding of
      these ranges strongly increases the violation of membrane native structure
      already at the stage of incubation with CPs, strengthening it during the freezing
      procedure. According to the perturbation effect on microsomal membranes the
      studied CPs can be arranged in a sequence: DMSO>PD>GL.

PMID- 16977489
TI  - Long-term stability of N1 sources using low-resolution electromagnetic
      tomography.
AB  - The purpose of this study was to investigate the long-term stability of auditory
      N1 sources using low-resolution electromagnetic tomography (LORETA). Data
      collected from 72 electrodes in ten young adult female participants were
      analyzed. For each participant, N1 peak amplitude and latency values at Cz
      (referred to M2) were compared for right, left, and bilateral stimulation across
      three separate recording sessions. Further, sources calculated by LORETA were
      analyzed in three regions of interest: right temporal, left temporal, and
      frontal. Peak amplitude and latency measurements were stable across session and
      ear of stimulation. Three-way RM-ANOVAs revealed relatively stable source
      amplitudes and stable three-dimensional locations of the sources in each region
      of interest with shifts of up to 2 cm around the mean locations. The 2 cm
      variability may be attributable both to normal hemispheric asymmetries and
      electrode placement variability. These results suggest that N1 scalp activity and
      its underlying sources are stable.

PMID- 16977490
TI  - Cortical characterization and inter-dipole distance between unilateral median
      versus ulnar nerve stimulation of both hands in MEG.
AB  - Contralateral somatosensory evoked fields (SEF) by whole head MEG after
      unilateral median and ulnar nerve stimulation of both hands were studied in 10
      healthy right-handed subjects. Major parameters describing cortical activity were
      examined to discriminate median and ulnar nerve evoked responses. Somatic
      sensitivity showed high similarity in the 4 study conditions for both hand and
      nerve. The brain SEFs consisted of 7-8 major peak stages with consistent
      responses in all subjects at M20, M30, M70 and M90. Comparable inter-hemispheric
      waveform profile but high inter-subject variability was found. Median nerve
      induced significantly shorter latencies in the early activities than those of the
      ulnar nerve. The 3D cortical maps in the post stimulus 450 ms timeframe showed
      for both nerves two polarity reversals, an early and a late one which is a new
      finding. Dipole characteristics showed differential sites for the M20 and M30 in
      the respective nerve. Higher dipole moments evoked by the median nerve were
      noticed when compared to the ulnar. Furthermore, the results of the dipole
      distances between both nerves for M20 were calculated to be at 11.17 mm +/- 4.93
      (LH) and 16.73 mm +/- 5.66 (RH), respectively after right hand versus left hand
      stimulation. This study showed substantial differences in the cortical responses
      between median and ulnar nerve. Especially the dipole distance between median and
      ulnar nerve on the cortex was computed accurately for the first time in MEG.
      Little is known however of the cortical responses in chronic pain patients and
      the parameter(s) that may change in an individual patient or a group. These
      results provide precise basis for further evaluating cortical changes in
      functional disorders and disease sequelae related to median and ulnar nerves.

PMID- 16977491
TI  - Electrophysiological and behavioral responses of a Cuban population of the sweet
      potato weevil to its sex pheromone.
AB  - The sex pheromone of feral sweet potato weevils Cylas formicarius elegantulus
      from Cuba was found, via solid-phase microextraction analysis, to be identical to
      (Z)-3-dodecenyl (E)-2-butenoate, a previously reported compound. Females emitted
      20 pg pheromone d(-1). In scanning electron microscopy studies carried out on the
      male antenna, we identified several types of sensilla: sensilla trichoidea of
      type 1 (ST1) as long hairs (100-150 microm), sensilla trichoidea of type 2 as
      short hairs (50-60 microm), sensilla basiconica of type 1 as thick pegs (20-25
      microm), sensilla basiconica of type 2 as curved pegs (10-15 microm), and
      sensilla basiconica of type 3 as thin and straight short pegs (15-20 microm). The
      same types were observed in female antennae but ST1 were far less abundant than
      in males. Sensilla chaetica were also found on the flagellum subsegments in both
      sexes. In electrophysiological tests, the crotonate function in the pheromone
      structure proved to be critical for activity since regular depolarizations (0.6
      0.8 mV) were obtained with puffs on 1 microg of the attractant, but not with
      puffs of the formate, acetate, propionate, or butyrate analogue of the pheromone.
      In a double dual-choice olfactometer, males showed maximum activity between the
      4th and the 8th hr of scotophase at a dose of 50-1000 ng of pheromone. In field
      tests, a correlation between the contents of the Z,E isomer in the pheromone
      formulation with activity was noticed, and baits containing this isomer of
      stereomeric purity >94% showed the highest attractivity. The presence of 5% of
      the Z,Z isomer in the lure did not induce any synergistic or inhibitory effect,
      and the alcohol precursor of the pheromone was inactive. The results show that
      use of a stereomerically pure pheromone may not be necessary in pest control
      strategies.

PMID- 16977493
TI  - Respondent-driven sampling in a study of drug users in New York City: notes from
      the field.
AB  - Beth Israel Medical Center (BIMC), in collaboration with the Centers for Disease
      Control (CDC) and the New York State Department of Health (NYSDOH), used
      respondent-driven sampling (RDS) in a study of HIV seroprevalence among drug
      users in New York City in 2004. We report here on operational issues with RDS
      including recruitment, coupon distribution, storefront operations, police and
      community relations, and the overall lessons we learned. Project staff recruited
      eight seeds from a syringe exchange in Lower Manhattan to serve as the initial
      study participants. Upon completion of the interview that lasted approximately 1
      h and a blood draw, each seed was given three coupons to recruit three drug users
      into the study. Each of the subsequent eligible participants was also given three
      coupons to recruit three of their drug-using acquaintances. Eligible participants
      had to have: injected, smoked or snorted an illicit drug in the last 6 months
      (other than marijuana), aged 18 or older, adequate English language knowledge to
      permit informed consent and complete questionnaire. From April to July 2004, 618
      drug users were interviewed, including 263 (43%) current injectors, 119 (19%)
      former injectors, and 236 (38%) never injectors. Four hundred sixty nine (76%)
      participants were men, 147 (24%) were women, and two (<1%) were transgender. By
      race/ethnicity, 285 (46%) were black, 218 (35%) Hispanic, 88 (14%) white, 23 (4%)
      mixed/not specified, and four (<1%) native American. Interviews were initially
      done on a drop-in basis but this system changed to appointments 1 month into the
      study due to the large volume of subjects coming in for interviews. Data
      collection was originally proposed to last for 1 year with a target recruitment
      of 500 drug users. Utilizing RDS, we were able to recruit and interview 118 more
      drug users than originally proposed in one quarter of the time. RDS was efficient
      with respect to time and economics (we did not have to hire an outreach worker)
      and effective in recruiting a diverse sample of drug users.

PMID- 16977492
TI  - Early activation of extracellular signal-regulated kinase signaling pathway in
      the hippocampus is required for short-term memory formation of a fear-motivated
      learning.
AB  - 1. According to its duration there are, at least, two major forms of memory in
      mammals: short term memory (STM) which develops in a few seconds and lasts
      several hours and long-term memory (LTM) lasting days, weeks and even a lifetime.
      In contrast to LTM, very little is known about the neural, cellular and molecular
      requirements for mammalian STM formation. 2. Here we show that early activation
      of extracellular signal-regulated kinases 1/2 (ERK1/2) in the hippocampus is
      required for the establishment of STM for a one-trial inhibitory avoidance task
      in the rat. Immediate posttraining infusion of U0126 (a selective inhibitor of
      ERK kinase) into the CA1 region of the dorsal hippocampus blocked STM formation.
      3. Reversible inactivation of the entorhinal cortex through muscimol infusion
      produced deficits in STM and a selective and rapid decrease in hippocampal ERK2
      activation.4. Together with our previous findings showing a rapid decrease in
      ERK2 activation and impaired STM after blocking BDNF function, the present
      results strongly suggest that ERK2 signaling in the hippocampus is a critical
      step in STM processing.

PMID- 16977495
TI  - Psychological and neurobehavioral comparisons of children with Asperger's
      Disorder versus High-Functioning Autism.
AB  - This study investigated personality and neurobehavioral differences between 16
      children with Asperger's Disorder, 15 children with High-Functioning Autism
      (HFA), and 31 controls, all ranging in age from 5-17 years, M age = 10.7 years,
      SD = 3.0. Parents rated their children's behaviors on a 44-item autistic symptoms
      survey and on the 200-item Coolidge Personality and Neuropsychological Inventory
      (Coolidge, Thede, Stewart, & Segal (2002a). The Coolidge Personality and
      Neuropsychological Inventory for Children (CPNI): Preliminary psychometric
      characteristics. Behavior Modification, 26, 550-566). The results indicated that
      the two clinical samples were significantly elevated on the Executive Function
      Deficits scale and Attention-Deficit/Hyperactivity Disorder (ADHD) scale compared
      to controls. There were more similarities than differences between the two
      clinical samples on the personality scales, although the Asperger's group scored
      significantly on the two scales with anxiety components.

PMID- 16977494
TI  - A comparative study of mortality among Puerto Rican injection drug users in East
      Harlem, New York, and Bayamon, Puerto Rico.
AB  - Drug users have been found to be at high risk of mortality but the mortality
      experience of Hispanic drug users remains understudied. This study assessed
      mortality among Puerto Rican injection drug users (IDUs) in New York City (NY),
      and in Puerto Rico (PR). Study subjects were 637 IDUs from NY and 319 IDUs from
      PR. Mortality was ascertained using data from the National Death Index. Annual
      mortality rate of the NY cohort was 1.3 per 100 person years compared to the PR
      cohort with a rate of 4.8. Compared to the Hispanic population of New York City,
      the standardized mortality ratio (SMR) of the NY cohort was 4.4. Compared to the
      population of Puerto Rico, the SMR of the PR cohort was 16.2. The four principal
      causes of death were: NY-HIV/AIDS (50.0%), drug overdoses (13.3%), cardiovascular
      conditions (13.3%), and pulmonary conditions (10.0%); PR-HIV/AIDS (37.0%), drug
      overdoses (24.1%), sepsis (13.0%), and homicide (11.1%). Modeling time to death
      using Cox proportional hazards regression, the relative risk of mortality of the
      PR cohort as compared to the NY cohort was 9.2. The other covariates found to be
      significantly associated with time to death were age, gender, education, social
      isolation, intoxication with alcohol, and HIV seropositivity. The large disparity
      in mortality rates found in this study suggests that health disparities research
      should be expanded to identify intra-group disparities. Furthermore, these
      results point to an urgent need to reduce excess mortality among IDUs in Puerto
      Rico.

PMID- 16977496
TI  - Do children with autism have a theory of mind? A non-verbal test of autism vs.
      specific language impairment.
AB  - Children with autism have delays in the development of theory of mind. However,
      the sub-group of children with autism who have little or no language have gone
      untested since false belief tests (FB) typically involve language. FB
      understanding has been reported to be intact in children with specific language
      impairment (SLI). This raises the possibility that a non-verbal FB test would
      distinguish children with autism vs. children with SLI. The present study tested
      two predictions: (1) FB understanding is to some extent independent of language
      ability; and (2) Children with autism with low language levels show specific
      impairment in theory of mind. Results confirmed both predictions. Results are
      discussed in terms of the role of language in the development of mindreading.

PMID- 16977497
TI  - Use of complementary and alternative medicine among children diagnosed with
      autism spectrum disorder.
AB  - This study examined the prevalence of the use of different types of conventional,
      complementary and alternative therapies by children diagnosed with an autism
      spectrum disorder (ASD). Of 112 families surveyed, 74% were using complementary
      and alternative medicine (CAM) for their child with ASD. CAM use was most
      strongly associated with parent report of child's diagnosis. Most CAM was
      reported by families to be either helpful or without effect, but not harmful. The
      main reasons for choosing CAM were related to concerns with the safety and side
      effects of prescribed medications. Conventional health care providers should be
      aware of the high prevalence of use among children with ASD and be prepared to
      discuss the use of CAM with families.

PMID- 16977499
TI  - Religious involvement and its association to risk behaviors among older youth in
      foster care.
AB  - This study examined religious involvement and its association to risk behaviors
      (sexual behavior, marijuana use, alcohol use, and cigarette use) among older
      youth in foster care (N=383). Three dimensions of religious involvement were
      assessed-church or religious service attendance, religious practices, and
      religious beliefs. Findings showed that gender, ethnic group membership, sexual
      abuse history, and placement type were significantly associated with older foster
      care youth's religious involvement. Hierarchical logistic regression analyses
      showed that religious service attendance was associated with reduced odds of
      youth's engagement in sexual behavior in the past 2 months and current use of
      cigarettes. In addition, greater religious beliefs were associated with a
      reduction in odds of youth's use of alcohol in the past 6 months and current use
      of cigarettes. The consideration of religious involvement as a positive influence
      and resource that may reduce unhealthy risk behaviors among older youth in foster
      care is discussed.

PMID- 16977500
TI  - Exemplars of community practice.

PMID- 16977498
TI  - Influence of dyslipidemia on moxidectin distribution in plasma lipoproteins and
      on its pharmacokinetics.
AB  - PURPOSE: We studied the influence of dyslipemia on the distribution of
      moxidectin, a potent antiparasitic drug of the macrocyclic lactone (ML) family,
      in plasma lipoproteins and on its pharmacokinetic behaviour. MATERIALS AND
      METHODS: Plasma samples from normolipidemic or dyslipidemic subjects were spiked
      with moxidectin (20 ng/ml). Rabbits fed with standard (n = 5) or cholesterol
      enriched diet (n = 5) were injected subcutaneously with moxidectin (300
      microg/kg) and blood samples were collected over 32 days. Lipoproteins were
      separated from plasma samples by ultracentrifugation on density gradients.
      Moxidectin and lipids were measured in plasma and in lipoproteins and the
      pharmacokinetic parameters calculated. RESULTS: In normolipidemic subjects or
      rabbits, the drug bound preferentially to HDL. In hyperlipidemic samples,
      moxidectin shifted to the VLDL-LDL fraction. In addition, hyperlipidemic rabbits
      had a 2.8-fold higher area under the plasma concentration versus time curve (AUC)
      and a lower clearance and volume of distribution when compared with controls.
      CONCLUSION: Dyslipidemia led to major changes in moxidectin plasma distribution
      and in drug disposition. Therefore, a high variability in moxidectin disposition
      might be expected in humans or animals liable to develop dyslipidemia, with a
      possible impact on the efficacy and safety of this class of drugs.

PMID- 16977501
TI  - Measuring the intrapersonal component of psychological empowerment: confirmatory
      factor analysis of the sociopolitical control scale.
AB  - The Sociopolitical Control Scale (SPCS) is a widely used measure of the
      intrapersonal component of psychological empowerment. Confirmatory factor
      analyses (CFA) were conducted with data from two samples to test the hypothesized
      structure of the SPCS, the potential effects of method bias on the measure's
      psychometric properties, and whether a revised version of the scale (SPCS-R)
      yielded improved model fit. Sample 1 included 316 randomly selected community
      residents of the Midwestern United States. Sample 2 included 750 community
      residents of the Northeastern U.S. Results indicated that method bias from the
      use of negatively worded items had a significant effect on the factor structure
      of the SPCS. CFA of the SPCS-R, in which negatively worded items were rephrased
      so that all statements were positively worded, supported the measure's
      hypothesized two-factor structure (i.e., leadership competence and policy
      control). Subscales of the SPCS-R were found reliable and related in expected
      ways with measures of community involvement. Implications of the study for
      empowerment-based research and practice are described, and strategies to further
      develop the SPCS are discussed.

PMID- 16977502
TI  - Integrating synapse proteomics with transcriptional regulation.
AB  - The mammalian postsynaptic proteome (PSP) comprises a highly interconnected set
      of approximately 1,000 proteins. The PSP is organized into macromolecular
      complexes that have a modular architecture defined by protein interactions and
      function. Signals initiated by neurotransmitter receptors are integrated by these
      complexes and their constituent enzymes to orchestrate multiple downstream
      cellular changes, including transcriptional regulation of genes at the nucleus.
      Genome wide transcriptome studies are beginning to map the sets of genes
      regulated by the synapse proteome. Conversely, understanding the transcriptional
      regulation of genes encoding the synapse proteome will shed light on synapse
      formation. Mutations that disrupt synapse signalling complexes result in
      cognitive impairments in mice and humans, and recent evidence indicates that
      these mutation change gene expression profiles. We discuss the need for global
      approaches combining genetics, transcriptomics and proteomics in order to
      understand cognitive function and disruption in diseases.

PMID- 16977503
TI  - Genotype by environment interaction in adolescents' cognitive aptitude.
AB  - In a replication of Turkheimer, Haley, Waldron, D'Onofrio, Gottesman II (2003,
      Socioeconomic status modifies heritability of IQ in young children. Psychological
      Science, 14:623-628), we investigate genotype-environment (G x E) interaction in
      the cognitive aptitude of 839 twin pairs who completed the National Merit
      Scholastic Qualifying Test in 1962. Shared environmental influences were stronger
      for adolescents from poorer homes, while genetic influences were stronger for
      adolescents from more affluent homes. No significant differences were found
      between parental income and parental education interaction effects. Results
      suggest that environmental differences between middle- to upper-class families
      influence the expression of genetic potential for intelligence, as has previously
      been suggested by Bronfenbrenner and Ceci's (1994, Nature-nurture
      reconceptualized in developmental perspective: a bioecological model
      Psychological Review, 101:568-586) bioecological model.

PMID- 16977504
TI  - Recurrent hepatitis C after living donor liver transplantation detected by Tc-99m
      GSA liver scintigraphy.
AB  - Recurrence of hepatitis C virus (HCV) after living donor liver transplantation
      was investigated using technetium-99m- diethylenetriaminepentaacetic acid
      galactosyl human serum albumin (Tc-99m-GSA) liver scintigraphy. Four patients
      with decompensated cirrhosis due to HCV infection were retrospectively reviewed
      in this study. Scintigraphy was performed to determine the hepatic uptake ratio
      of the tracer corrected for disappearance from the blood, as well as the maximal
      removal rate of the tracer by hepatocytes, as parameters of hepatic functional
      reserve. In all patients, serum HCV ribonucleic acid (RNA) was detected 3 months
      after transplantation. The corrected hepatic uptake ratio and removal rate showed
      little change after transplantation in two patients without the recurrence of HCV
      infection. In another two patients, these levels were decreased at 3 months after
      transplantation. In one patient, recurrent HCV infection was diagnosed by
      confirmatory histologic examination at 12 months after transplantation. In the
      other patient, both levels declined further at 8 months. Although treatment was
      initiated with a combination of interferon plus ribavirin, this patient died of
      progressive hepatic failure. In conclusion, a decrease in scintigraphic
      parameters at 3 months after transplantation suggests recurrent HCV infection
      affecting the graft. Tc-99m-GSA liver scintigraphy is a useful noninvasive method
      for evaluating graft functional reserve.

PMID- 16977505
TI  - Is hepatitis C virus positivity a contributing factor to occult hepatitis B virus
      infection in hemodialysis patients?
AB  - Hepatitis B (HBV) infections continue to occur in adult hemodialysis units.
      Occult HBV infection (serum hepatitis B surface antigen [HBsAg] negative but HBV
      DNA positive) may be a contributing factor in these patients. This study was
      designed to (1) investigate the prevalence of occult HBV infection in
      hemodialysis patients and (2) compare the prevalence of occult HBV infection
      among hepatitis C (HCV)-positive and HCV-negative hemodialysis patients. The
      study included 138 patients on chronic hemodialysis. Eighty-four patients were
      HCV positive and 54 were HCV negative. HBV DNA testing was performed by
      polymerase chain reaction. We also recorded general characteristics of the
      patients, duration of hemodialysis, and serum alanine aminotransferase and
      aspartate aminotransferase levels. Twenty-one (15.2%) of the 138 hemodialysis
      patients were HBV DNA positive. Nine (16.6%) of the 54 anti-HCV antibody negative
      hemodialysis patients were HBV DNA positive. Twelve (14.2%) of the 84 anti-HCV
      antibody positive patients were HBV DNA positive. The prevalence in anti-HCV Ab
      positive and negative hemodialysis patients were same (P > .05). Hemodialysis
      duration, demographic features, and biochemical parameters were not significantly
      different in patients with and without occult HBV infection in both HCV-positive
      and -negative hemodialysis patients (P > .05). HCV positivity is not a
      contributing factor to occult HBV infection in hemodialysis patients. None of the
      parameters tested help to distinguish patients with occult HBV infection from
      those who are HBV DNA negative.

PMID- 16977507
TI  - A comparison between sodium alginate and magaldrate anhydrous in the treatment of
      patients with gastroesophageal reflux symptoms.
AB  - The aims of the present study were to compare effects of sodium alginate and the
      antacid magaldrate anhydrous in adults with gastroesophageal reflux (GOR)
      symptoms. Patients with heartburn and/or acid regurgitation for at least 3 days
      in the week before the study started (n=203) were randomized to receive a single
      dose of sodium alginate or magaldrate anhydrous at the onset of symptoms during a
      3-day run-in period. Patients with symptoms during the run-in (n=191) were
      rerandomized to receive a 14-day treatment with either drug given as four daily
      doses. A speed of action < or =30 min was significantly more frequent among
      patients in the alginate group (49.4% vs. 40.4%; P=0.0074). A trend toward a more
      prolonged duration of action (median: 16.5 vs. 12.7 hr) and a greater sum of the
      symptom intensity difference (median: 40.0 vs. 31.0) was observed in the sodium
      alginate group. Total disappearance of symptoms was reported in 81.6% and 73.9%
      of patients in the sodium alginate group and magaldrate group, respectively. We
      conclude that sodium alginate was faster than magaldrate in relieving GRO
      symptoms and showed a tendency toward a more prolonged duration of action and a
      higher level of efficacy.

PMID- 16977506
TI  - Single-photon emission computed tomography in the screening for postoperative
      pulmonary embolism.
AB  - The aim of the study was to evaluate the usefulness of serial lung perfusion
      scintigraphy prospectively using single-photon emission computed tomographic
      image (SPECT) in screening for pulmonary embolism (PE) after elective surgery for
      gastrointestinal malignancy. PE was examined pre- and postoperatively with SPECT.
      Diagnosis of PE was based on segmental perfusion defect visualization in at least
      two of three planes on a SPECT image compared with preoperative SPECT images.
      Final diagnosis was determined by detection of embolus with multidetector helical
      CT (MDCT). No perioperative anticoagulant was used. Thirty-four patients were
      enrolled. One patient was excluded because of thrombophilia. In preoperative
      scans, nonsegmental defects were detected in 11 and a segmental defect in 1
      patient, who was then diagnosed as PE preoperatively. Among 21 patients with
      normal preoperative SPECT, 2 had nonsegmental and 5 had segmental defects
      postoperatively. Among 11 patients with nonsegmental preoperative SPECT, 7 had
      nonsegmental and 4 had segmental defects postoperatively. Postoperative segmental
      defects were differentiated by their shape only and there was no need to compare
      pre- and postoperative SPECT. MDCT confirmed four patients with PE among nine
      with segmental defects postoperatively. Our results of screening for PE by
      visualization at least two planes of SPECT images suggest that postoperative
      SPECT scan is suitable for the diagnosis of postoperative PE.

PMID- 16977508
TI  - The effect of traction on esophageal structure in children with long-gap
      esophageal atresia.
AB  - We examined the esophageal structure in children who underwent traction to
      achieve primary repair of long-gap esophageal atresia. High-resolution ultrasound
      was used to compare thickness of the proximal and distal esophagus in children
      who had traction to achieve primary repair (n=15) to cases of esophageal atresia
      with shorter gaps that did not require traction (n=8). The muscularis propria of
      the upper esophagus was thicker in the traction compared to the non-traction
      group, though not statistically significant (respectively, 0.79 (0.18) mm vs.
      0.71 (0.16) mm; p=0.29), measurements were similar for the lower esophagus
      (respectively, 0.79 (0.21) mm vs. 0.75 (0.13) mm; p=0.64). Combined mucosa and
      submucosa was very similar in both groups for the upper (respectively, 1.03
      (0.15) mm vs. 1.04 (0.16) mm; p=0.95) and lower esophagus (respectively, 1.09
      (0.23) mm vs. 1.01 (0.13) mm; p=0.37). The thickness of individual mural layers
      is maintained after increasing esophageal length with traction.

PMID- 16977509
TI  - Dopamine D2 receptor polymorphisms in inflammatory bowel disease and the
      refractory response to treatment.
AB  - Dopamine and its receptors may be involved in inflammatory reaction. The
      availability of this molecule depends on its receptors. The DRD2 gene, which
      codifies for the D2 dopamine receptor, has several polymorphisms. In this study,
      the DRD2 TaqIA polymorphism, which confers a decreased receptor density, was
      evaluated in 313 individuals including 220 inflammatory bowel disease patients
      (143 patients with Crohn's disease and 77 with ulcerative colitis) and in 93
      healthy blood donors. The analysis was carried out by PCR-RFLP techniques. The
      frequencies of A (1) A (1) and A (2) A (2) genotypes were similar among Crohn's
      disease, ulcerative colitis patients, and health controls. Also, the genotype
      frequency was similar in different groups of disease localization, behavior, and
      age of disease onset. However, the Crohn's disease patients carriers of A (2) A
      (2) genotype showed a lower risk for development refractory Crohn's disease (37
      out 65) than A (1) A (1) and A (1) A (2) carriers (28 out of 65) [(OR=0.4, 95% CI
      0.21-0.87; p=0.02)]. Our results support an involvement of the dopamine receptor
      in inflammatory bowel disease and suggest a new potential target for therapy in
      refractory Crohn's disease patients.

PMID- 16977510
TI  - Glacial effects on sequence divergence of mitochondrial COII of Polyura
      eudamippus (Lepidoptera: Nymphalidae) in China.
AB  - Sequence divergence of mitochondrial COII was analyzed in 50 specimens belonging
      to five subspecies of Polyura eudamippus (Lepidoptera: Nymphalidae) collected
      from southern China. There were nine haplotypes in the 405 bp of partial COII
      sequence. Distribution of the five subspecies was primarily consistent with the
      spatial distribution of haplotypes. The K (st) statistic showed genetic
      differentiation among these subspecies, except between the pair of P. e.
      kuangtungensis and P. e. formosana, which were separated by the Taiwan Strait.
      This is consistent with the 10,000-year history of the Taiwan Strait, not long
      enough for detectable differentiation. The present distribution pattern of COII
      haplotypes of P. eudamippus should be shaped by the alteration of Pleistocene
      glaciations, and Yunnan might be the refugium of P. eudamippus in the ice age,
      judging from the abundant haplotypes remaining. There were two routes for P.
      eudamippus in the postglacial expansion, one northward to Sichuan, Chongqing, and
      Hubei and another eastward to the southeastern coast of mainland China and Taiwan
      Island. Because the haplotype of butterflies on Hainan Island (P. e. whiteheadi)
      was completely different from that of mainland China, it was estimated that
      butterflies on Hainan Island might be from the Indo-China Peninsula rather than
      from mainland China.

PMID- 16977511
TI  - Mitochondrial DNA restriction map and cytochrome c oxidase subunits I and II
      sequence divergence of corn stalk borer Sesamia nonagrioides (Lepidoptera:
      Noctuidae).
AB  - Corn stalk borer Sesamia nonagrioides (Lefebvre) (Lepidoptera: Noctuidae) is
      among the most important insect pests of corn in the Mediterranean basin. The
      mitochondrial DNA of this insect was purified and a restriction map was
      constructed. The size of the mtDNA genome is 16.3 kb. Genetic analysis of four
      corn stalk borer populations, collected from Greece (three populations) and Spain
      (one population), was undertaken using DNA sequences of the mtDNA cytochrome
      oxidase (CO) I and II genes. Sequencing of a 2079 bp region of these genes
      revealed 25 polymorphic sites among the populations. Five molecular RFLP markers,
      located in the mtDNA COI and COII genes, were surveyed, and two different
      haplotypes were detected. Phylogenetic analysis based on COI/COII nucleotide
      sequences revealed genetic differentiation between samples, and the results are
      discussed in relation to the geographic distribution of the corn stalk borer in
      two Mediterranean countries.

PMID- 16977512
TI  - The association between polymorphic genotypes of glutathione S-transferases and
      COPD in the Turkish population.
AB  - Although smoking is regarded as the most important causal factor in chronic
      obstructive pulmonary disease (COPD), only 10-20% of smokers develop symptomatic
      COPD, which indicates the presence of genetic predisposing factors in its
      pathogenesis. This study investigates the association between gene polymorphysims
      of glutathione S-transferases (GSTs) and COPD. Blood samples were taken from 149
      patients and 150 healthy controls. Polymorphisms of GSTT1, GSTM1, and GSTP1 were
      genotyped using Real-Time PCR. Multivariate logistic regression was used to
      calculate odds ratios (ORs) and 95% confidence intervals between specific
      genotypes and COPD. There was no difference in the frequencies of the genotypes
      of GSTM1 and GSTT1 between the groups, but the GSTP1 Ile/Ile genotype was
      significantly higher in the patients than in the controls (61.1% vs. 38%). GSTP1
      Ile/Val and Val/Val genotypes were associated with a decreased risk of COPD when
      compared to the Ile/Ile genotype (2.12-fold and 4-fold, respectively). Thus we
      suggest that the Val allele of GSTP1 may have a protective effect for development
      of COPD. Furthermore, when we evaluated the association between GSTP1 genes and
      smoking status, smokers with the GSTP1 Ile allele had an increased risk for the
      development of COPD. Among the combinations of the genotypes, the combination of
      GSTM1, GSTT1 null, and GSTP1 Val/Val was associated with the maximal increased
      risk (12-fold) of COPD. Thus to explain the ethiopathogenesis of COPD,
      investigation of a single gene family is inadequate. Based on our results and the
      previous data, further studies should be focused on the GSTP1 gene and the
      interactions with other genes such as polymorphisms of N-acetyltransferases,
      GSTM1 and GSTT1, microsomal epoxide hydrolase, and allelic variants of cytochrome
      P450.

PMID- 16977513
TI  - Characteristics of assaultive psychiatric patients: fifteen-year analysis of the
      Assaulted Staff Action Program (ASAP).
AB  - This study reports on a fifteen-year longitudinal analysis of the characteristics
      of assaultive patients in one public-sector mental health care system. The data
      were gathered within the context of the Assaulted Staff Action Program (ASAP), a
      crisis intervention service for staff victims. The fifteen-year findings were
      consistent with previous worldwide research on assaultive patients and included
      both older male patients with schizophrenia and younger personality-disordered
      patients as high-risk assailants. Both groups had appreciable histories of
      violence toward others, personal victimization, and substance use disorders. The
      role of these three clinical variables in association with subsequent assaults,
      the role of trauma in female assailants, and the consistency of the fundamental
      characteristics of assaultive patients during several service system initiatives
      were examined. Implications for research and intervention are discussed.

PMID- 16977515
TI  - Determination of selenium concentration in serum and toenail as an indicator of
      selenium status.

PMID- 16977516
TI  - Marine algal toxins in shellfish from shanghai markets and original sources
      following a large scale red tide occurrence.

PMID- 16977517
TI  - Differential sensitivity to human influence in juvenile Semimytilus algosus
      (Gould, 1850) (Mollusca: Mytilidae) from four coastal sites in south-central
      Chile.

PMID- 16977518
TI  - Heavy metals in the tissues of the sea turtle Lepidochelys olivacea from a
      nesting site of the northwest coast of Mexico.

PMID- 16977519
TI  - Metal concentrations in blue crab (Callinectes sapidus) and mullet (Mugil
      cephalus) in Iskenderun Bay, Northern East Mediterranean, Turkey.

PMID- 16977520
TI  - Phytotoxic effect of coal mine effluent on growth behavior, betabolic changes,
      and metal accumulation in rice plants (Oryza sativa L.) c.v. IR-36.

PMID- 16977521
TI  - Metal content of marine mussels from Western Scheldt Estuary and nearby protected
      marine bay, The Netherlands: impact of past and present contamination.

PMID- 16977522
TI  - Comparison of PAH and nonylphenol uptake by carp (Cyprinus carpio) and
      semipermeable membrane devices (SPMDs) from water.

PMID- 16977523
TI  - Biosorption of metal ions from aqueous solution and electroplating industry
      wastewater by Aspergillus japonicus: phytotoxicity studies.

PMID- 16977524
TI  - Effect of mixtures of pesticides used in the direct seeding technique on
      nontarget plant seeds.

PMID- 16977525
TI  - Toxic equivalent (TEQ) levels and characteristics of PCDD/DF and CoPCB
      concentrations in marine foods in Japan.

PMID- 16977526
TI  - Stability studies of selected phenoxyacid herbicides in water samples and
      determination of their transformation products.

PMID- 16977527
TI  - Phthalate ester pollution in urban soil of Beijing, People's Republic of China.

PMID- 16977528
TI  - Effect of soil type, soil pH, and microbial activity on persistence of clodinafop
      herbicide.

PMID- 16977529
TI  - Carbofuran sorption kinetics by corn crop soils.

PMID- 16977530
TI  - Atmospheric concentrations of sulphur dioxide in and around a typical Indian
      petroleum refinery.

PMID- 16977531
TI  - Distribution of cobalt, lead, and nickel in various vegetables from
      Kahramanmaras, Turkey.

PMID- 16977532
TI  - Gallium, indium, and arsenic pollution of groundwater from a semiconductor
      manufacturing area of Taiwan.

PMID- 16977533
TI  - Effects of remedial treatment on phosphorus availability in an arsenical
      pesticide contaminated soil.

PMID- 16977534
TI  - Characterization and source identification of major inorganic ions in
      precipitation of Nagpur, India.

PMID- 16977535
TI  - Heavy metal contamination in vegetables grown in wastewater irrigated areas of
      Varanasi, India.

PMID- 16977541
TI  - [Abstracts of the 8th Congress of the German Society of Gerontology and
      Geriatrics, 28-30 September 2006, Freiburg].

PMID- 16977546
TI  - Attention-deficit-/hyperactivity disorder (ADHD).

PMID- 16977545
TI  - The Wuerzburg Research Initiative on Adult Attention-Deficit/Hyperactivity
      Disorder (WURIN-AADHD): multi-layered evaluation of long-term course.
AB  - Although the neurobiological basis of the clinical entity of attention
      deficit/hyperactivity disorder (ADHD) is evident, data from studies on
      pathomechanism-phenotype correlations are inconsistent. There are several obvious
      limitations of the DSM-IV diagnostic criteria to describe an adequate phenotype
      of adult ADHD. A dimensional model of neurobiologically based endophenotypes is
      therefore more likely to be compatible with the genetic model of quantitative
      trait loci. The primary goal of the Wuerzburg Research Initiative on Adult
      Attention-Deficit/Hyperactivity Disorder (WURIN-AADHD) is to test the validity of
      two endophenotypes, deficit in response inhibition and impairment of working
      memory, using various psychometric and neurobiological strategies of
      investigation in adult patients with ADHD. An additional objective is the
      investigation of the long-term course of adult ADHD. The conclusive description
      of valid endophenotypes of ADHD is an ongoing process that may result in a
      comprehensive neurobiological model for ADHD or its symptom dimensions
      integrating genetic, neural, cognitive, and behavioral mechanisms. This model
      will eventually facilitate description of complete causal connections occurring
      across the lifespan from early development to adulthood and is also likely to
      accelerate development of more specific and efficient therapeutic strategies in
      adult ADHD.

PMID- 16977547
TI  - Attention-deficit/hyperactivity disorder (ADHD) in the course of life.
AB  - ADHD is a pervasive disorder that extensively impairs the quality of life and
      that can lead to serious secondary problems. Contrary to the prior assumption
      long-term studies have demonstrated that the disorder is not limited to childhood
      and adolescence. Unfortunately appropriate criteria for adults with ADHD are not
      given in the ICD-10. The clinical experience indicates substantial difficulties
      of adults, whose ADHS is not diagnosed and treated. They often cause extensive
      costs for the welfare system. The evidence-based psychiatric treatment is highly
      effective and inexpensive.

PMID- 16977548
TI  - Psychiatric comorbidity in adults with attention-deficit/hyperactivity disorder
      (ADHD).
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a chronic, lifelong disorder
      with childhood-onset, which seriously impairs the affected adults in a variety of
      daily living functions like educational and occupational functioning, partnership
      and parenting. ADHD is associated with a high percentage of comorbid psychiatric
      disorders in every lifespan. In adulthood between 65-89% of all patients with
      ADHD suffer from one or more additional psychiatric disorders, above all mood and
      anxiety disorders, substance use disorders and personality disorders, which
      complicates the clinical picture in terms of diagnostics, treatment and outcome
      issues. The present overview provides information of comorbid psychiatric
      disorders in adults with ADHD, underlying associations and clinical implications.

PMID- 16977549
TI  - Psychopathological rating scales for diagnostic use in adults with attention
      deficit/hyperactivity disorder (ADHD).
AB  - The diagnosis of attention-deficit hyperactivity disorder (ADHD) in adults is a
      complex procedure which should include retrospective assessment of childhood ADHD
      symptoms either by patient recall or third party information, diagnostic criteria
      according to DSM-IV, current adult ADHD psychopathology including symptom
      severity and pervasiveness, functional impairment, quality of life and
      comorbidity. In order to obtain a systematic database for the diagnosis and
      evaluation of the course ADHD rating scales can be very useful. This article
      reviews rating instruments that have found general acceptance. The Wender-Utah
      Rating Scale (WURS) and the Childhood Symptoms Scale by Barkley and Murphy try to
      make a retrospective assessment of childhood ADHD symptoms. The Connors Adult
      ADHD Rating Scales (CAARS), the Current Symptoms Scales by Barkley and Murphy
      (CSS), the Adult Self Report Scale (ASRS) by Adler et al. and Kessler et al. or
      the Attention Deficit Hyperactivity Disorder--Self Report Scale (ADHD-SR by
      Rosler et al.) are self report rating scales focusing mainly on the DSM-IV
      criteria. The CAARS and the CSS have other report forms too. The Brown ADD Rating
      Scale (Brown ADD-RS) and the Attention Deficit Hyperactivity Disorder--Other
      Report Scale (ADHD-OR by Rosler et al.) are instruments for use by clinicians or
      significant others. Both self rating scales and observer report scales quantify
      the ADHD symptoms by use of a Likert scale mostly ranging from 0 to 3. This makes
      the instruments useful to follow the course of the disease quantitatively.
      Comprehensive diagnostic interviews not only evaluate diagnostic criteria, but
      also assess different psychopathological syndrome scores, functional disability
      measures, indices of pervasiveness and information about comorbid disorders. The
      most comprehensive procedures are the Brown ADD Diagnostic Form and the Adult
      Interview (AI) by Barkley and Murphy. An instrument of particular interest is the
      Wender Reimherr Interview (WRI) which follows a diagnostic algorithm different
      from DSM-IV. The interview contains only items delineated from adult
      psychopathology and not derived from symptoms originally designed for use in
      children. Other instruments focus on functional impairment, quality of life,
      comorbid disorders, gender effects and specific psychopathological models.

PMID- 16977550
TI  - Anatomical and functional brain imaging in adult attention-deficit/hyperactivity
      disorder (ADHD)--a neurological view.
AB  - In this review, we discuss current structural and functional imaging data on ADHD
      in a neurological and neuroanatomical framework. At present, the literature on
      adult ADHD is somewhat sparse, and so results from imaging have to therefore be
      considered mainly from the childhood or adolescence perspective. Most work has
      considered the impairment of executive functions (motor execution, inhibition,
      working memory), and as such a number of attention networks and their anatomical
      correlates are discussed in this review (e.g. the cerebello-(thalamo-)-striato
      cortical network seems to play a pivotal role in ADHD pathology from childhood to
      adulthood). The core findings in ADHD imaging are alterations in the architecture
      and function of prefrontal cortex and cerebellum. The dorsal part of anterior
      cingulated cortex (dACC) is an important region for decision making, and
      executive control is impaired in adult ADHD. Finally, dysfunction of basal
      ganglia is a consistent finding in childhood and adulthood ADHD, reflecting
      dysregulation of fronto-striatal circuitry. The cerebellum, and its role in
      affect and cognition, is also persistently implicated in the pathology of ADHD.

PMID- 16977551
TI  - Differential diagnosis and comorbidity of attention-deficit/hyperactivity
      disorder (ADHD) and borderline personality disorder (BPD) in adults.
AB  - Attention-deficit/hyperactivity disorder (ADHD) in adults and borderline
      personality Disorder (BPD) share some similar clinical features (e. g.
      impulsivity, emotional dysregulation, cognitive impairment). ADHD in childhood
      has been reported to be highly associated with the diagnosis of BPD in adulthood
      and adult ADHD often co-occurs with BPD. Treatment studies revealed an efficacy
      of dialectical behavioral therapy (DBT) and DBT-based psychotherapy,
      respectively, in BPD and adult ADHD as well as neuroimaging and
      psychopharmacological studies showed some evidence for a potential common
      neurobiological dysfunction suggesting the hypothesis that ADHD and BPD may not
      be two distinct disorders, but represent at least in a subgroup of patients two
      dimensions of one disorder.

PMID- 16977552
TI  - A new understanding of attention-deficit disorders--beyond the age-at-onset
      criterion of DSM-IV.
AB  - For decades, ADHD has been seen primarily as a behavior disorder affecting only
      young children, primarily boys, causing them to be inattentive and disruptive in
      school. Research has now established that ADHD affects females as well as males,
      and that impairing symptoms, for most, persist into adulthood. It has also been
      shown that this disorder impacts many aspects of life that extend well beyond
      problems in school. This disorder impairs not only one's ability to sit still and
      listen, but also the capacity to organize tasks and materials, to sustain effort
      on tasks, and to utilize short-term memory for daily activities. Studies of
      children, adolescents, and adults with ADHD indicate that many suffer from a
      variety of cognitive impairments that extend beyond symptoms listed in the DSM-IV
      diagnostic criteria for ADHD. These include chronic problems in regulating
      alertness, in reading comprehension, and in modulating emotions, that occur more
      frequently in persons with ADHD than in the general population. This article
      describes recent research findings demonstrating the wide range of cognitive
      impairments associated with ADHD, which are related to a new model of ADHD, such
      as developmental impairment of executive functions of the brain.

PMID- 16977553
TI  - [Neurologist regarding the dependence law].
AB  - INTRODUCTION: The approval of the "project of promotion of personal autonomy and
      care to people on dependence" situation law now opens the parliamentary process
      to the approval of the mentioned law around October- November 2006. Should the
      neurologist know its content and express his/her opinion about it? DEVELOPMENT:
      We analyze the role of neurological disorders as a cause of dependence, the law
      principles, the involvement of the neurologist in the social-health care
      coordination, the health administrations involved in the law development and the
      role of Spanish Neurological Society and regional societies as mediators with the
      different health administration, the involvement of the neurologist in
      accreditation, education, research and development, independence promotion, and
      dependence evaluation. CONCLUSION: Given that the project will be modified in the
      course of its parliamentary process, and the relevance of its reglamentary
      development, the door has been left open for the role of the neurologist to be
      accepted at the moment when the law is developed and applied. In any case, the
      well-being and quality of life of our patients should not be overlooked. We think
      that the Spanish Neurological Society will have an important role in this
      process.

PMID- 16977554
TI  - [The costs of a multiple sclerosis relapse in Catalonia (Spain)].
AB  - INTRODUCTION: The objective of this study is to calculate direct, indirect and
      intangible costs of a relapse in multiple sclerosis (MS) in our cohort of
      patients. METHODS: Data from patient questionnaires, hospital charts, Catalan
      Public Healthcare System tariffs and Catalan Statistics Institute. We employed a
      cost-of-illness method. The human capital approach was used to estimate indirect
      costs, and quality-of-life measurements were used to estimate intangible costs.
      RESULTS: 148 MS patients monitored in our MS-Unit consecutively answered the
      questionnaire elaborated. We calculated 1,498.5-1,537.9 euros for direct costs
      (hospital admission and outpatient, respectively) and 1,530.6 euros for indirect
      costs. We estimated an average total cost of 3,048.8 euros per patient/relapse.
      We also calculated intangible costs, 539 euros per patient and relapse, which
      should be added to the previous figure. CONCLUSIONS: The total cost of a MS
      relapse in our population (3,048.8 euros) is lower than the cost reported in the
      literature. The economic impact of MS is due to its disabling progression rather
      than to relapses

PMID- 16977555
TI  - [Short form 36 health questionnaire in hemiplegic patients 2 years after stroke].
AB  - INTRODUCTION: Many studies show that subjects with sequelae after stroke have a
      worse health perception in western societies. Due to the shortage of papers on
      the Spanish population in this regard, a study was carried out to assess health
      perception in hemiplegic patients 2 years after stroke in comparison with that of
      the general population and correlate health perception with demographic, clinical
      and functional variables. METHODS: Cross-sectional study of 212 community stroke
      survivors. The main variables collected were: health perception assessed with the
      Short Form 36 (SF-36), disability assessed with the motor Functional Independence
      Measure (FIM) and Geriatric Depression Scale (GDS). Statistical tests used: chi2,
      Student t test and Spearman correlation coefficient. RESULTS: In comparison with
      the Spanish general population, health perception in hemiplegic male stroke
      patients is diminished in all areas. In hemiplegic female patients, physical
      function is the only subscale significantly affected in all age groups. Variables
      related to worse health perception are: presence of depression, dependence and
      the belief of the need for kind of social support, A significant correlation was
      observed between SF-36 values and the motor FIM (r = 0.737 with physical
      function) and the GDS (r = -0.821 with mental health). CONCLUSIONS: Health
      perception in hemiplegic patients 2 years after stroke is diminished in
      comparison with that 348 of the general population. Factors which determine worst
      health perception are depression, motor dependence, need of caregiver assistance
      and need of social support.

PMID- 16977556
TI  - [Mitochondrial DNA deletions in Kearns-Sayre syndrome].
AB  - INTRODUCTION: Kearns-Sayre syndrome (KSS) is a mitochondrial disorder
      characterized by progressive external ophthalmoplegia, pigmentary retinopathy,
      onset before 20 years, and ragged-red fibers on muscle biopsy. KSS has been
      associated to mitochondrial DNA (mtDNA) mutations. We report neurological
      manifestations and mtDNA deletions in KSS. METHODS: Six KSS patients underwent
      neurological examination, biochemical analysis (muscle enzymes, lactate,
      cerebrospinal fluid analysis), electromicrography, muscle biopsy (Gomori stain,
      electronic microscopy), electrocardiogram, echocardiography, MRI/CT scan. MtDNA
      deletions were studied in blood and muscle samples using Southern blotting and
      long polymerase chain reaction. RESULTS: Four males and two females (mean age:
      27.7 years; range: 17-42; mean age at onset: 8.2 years) were studied. Initial
      symptoms were ptosis and gaze restriction, fatigue, exercise intolerance and
      proximal limb weakness. Syncope and neurosensory hypoacusia were initial symptoms
      in two patients. All of them presented a unique deletion in the mitochondrial
      genome, in heteroplasmy, and their size was in the range of 4,420 and 9,437 basis
      pairs. Three of these deletions are reported for the first time in this article.
      Most of the deletions are flanked by small direct repeats elements. CONCLUSIONS:
      Proximal muscle weakness and fatigue appear frequently in KSS patients during
      follow up. The syndrome in these patients has been caused by mtDNA deletions.

PMID- 16977557
TI  - [Treatment of Parkinson disease: therapeutic reserve of the dopaminergic
      agonist].
AB  - Parkinson's disease (PD) is a neurodegenerative, chronic and progressive disease
      whose evolutive course changed significantly after the introduction of levodopa.
      However, no antiparkinsonian drug has been able to stop the progression of PD.
      Thus, as the years have passed, greater drug doses have been necessary, either
      alone or in different combinations. Therefore, it is useful to have drugs with a
      wide threshold between effective dose and maximum tolerated dose. The concept of
      therapeutic reserve (TR) can be considered equivalent to therapeutic index or
      therapeutic window and could be defined as the difference between the dose needed
      to achieve an optimum therapeutic response at a given time and the dose that
      causes adverse events (maximum recommended dose or "ceiling dose"). This
      difference indicates the threshold that makes it possible to use higher doses as
      the disease advances to maintain an optimum clinical effect without the
      appearance of adverse events. This concept is important in the case of
      dopaminergic agonists whose efficacy seems to be similar in the daily clinical
      practice. Although there are no direct comparative studies, the analysis of the
      results of different studies suggests that the TR of ropinirole is superior to
      that of other dopaminergic agonists. The first effective dose, defined as an
      improvement superior to 30 % is observed with 9 mg/day in 75 % of the patients
      while the maximum recommended dose is 24 mg/day. This threshold is less with
      other dopamine agonists.

PMID- 16977558
TI  - [Dropped head syndrome secondary to nemalinic myopathy].

PMID- 16977559
TI  - [Spinal leptomeningeal metastasis from cerebral glioblastoma: case report].
AB  - INTRODUCTION: Glioblastoma multiforme (GBM) is the most common primary malignant
      tumor of the central nervous system. Its tendency to infiltrate and recur locally
      is well known. Spinal leptomeningeal metastasis (SLM) due to a GBM are well
      documented at autopsy in patients previously diagnosed of GBM, however, systemic
      dissemination with symptomatic leptomeningeal metastasis is quite rare. Most of
      the time it is diagnosed late and misdiagnosis is a common problem. CASE REPORT:
      We present a case of a 65-year-old man with a right temporal GBM treated by
      surgical resection, radiotherapy and chemotherapy, who is readmitted 10 months
      later as he developed an ataxic gait. A new cerebral magnetic resonance imaging
      (MRI) showed multiple cerebellar metastasis. He also reported intense lumbar pain
      on the new admission, increasing in intensity and that was followed by flaccid
      paraparesis two weeks later. Multiple spinal metastasis deposits were documented
      by a contrast enhanced spinal MRI. CONCLUSIONS: SLM need to be suspected in
      patients with a past history of intracranial GBM, who present with clinical
      features that can not been explained by the primary lesion. Awareness of this
      complication might facilitate more rapid diagnosis and treatment. A discussion is
      made regarding SLM in patients with GBM with reference to the medical literature.

PMID- 16977560
TI  - [Long-term risk of relapses in Tolosa-Hunt syndrome].
AB  - INTRODUCTION: The reviewed diagnostic criteria of Tolosa- Hunt sindrome (THS) by
      the International Classification of Headache Disorders (ICHD-II, 2004) includes
      demonstration of inflammatory changes by magnetic resonance imaging (MRI) in the
      cavernous sinus region as an alternative to biopsy. Careful follow-up is required
      to exclude other possible causes of painful ophthalmoplegia. It remains unclear
      for how long such close observation should be extended to assure the diagnosis
      nor whether THS represents a self-limited condition in the long-term. CASE
      REPORT: An observational study along 13 years of a patient fulfilling current
      ICHD-II criteria for THS to clarify the natural history of the disorder. RESULTS:
      We witnessed three episodes, the presenting one causing severe left orbital pain,
      ipsilateral abducens palsy , and hypoesthesia in the territory of the ophthalmic
      branch of the trigeminal nerve. Gadolinium MRI showed enhancement of tissue
      infiltrating the lateral wall of the carotid sinus. A relapse 21 months later
      caused involvement of left oculomotor and abducens nerves in addition to orbital
      pain which responded rapidly to steroids. Ensuing remission maintained for up to
      11 years concluded in a new relapse again characterized by severe ipsilateral
      orbital pain and frontal numbness, but no ophthalmoplegia. A gadolinium-MRI did
      not show enhancement on this occasion despite prompt response to steroids.
      CONCLUSION: The risk of relapses in THS and its response to steroids may be
      maintained for as long as 13 years.

PMID- 16977561
TI  - [Tuberous sclerosis complex type 1 (TSC1): diagnostic significance of the
      cutaneous mini-lesions in a familial presentation].
AB  - We present a family with tuberous sclerosis complex type 1 (TSC1). The family is
      formed by six patients. Two sibs, female and male, both patients having minor
      signs of the disorder. The woman have two daughters, one of them with severe
      clinical and radiological features of TSC1, and the other who only has a small
      cutaneous acromic spot. The man has two sons, one with severe features of TSC1,
      and the other with cutaneous mini-lesions. DNA study of the two cousins, woman
      and man, with cutaneous mini-lesions, showed a mutation in the chromosome 9 (1749
      del GA) (TSC1 ex 15) in both patients. No pathogenic mutation in the TSC2 gene
      was detected in the two cousins.

PMID- 16977562
TI  - [Mild cognitive alteration and alcohol consumption].

PMID- 16977563
TI  - [From expansion to reality, what to do with trained neurologists?].

PMID- 16977564
TI  - [On the future of the young neurologist in Spain].

PMID- 16977566
TI  - Diagnosis of inherited von Willebrand disease: a clinical perspective.
AB  - von Willebrand disease (VWD) is the most frequent inherited disorder of
      hemostasis and is due to quantitative (types 1 and 3) or qualitative (type 2)
      defects of von Willebrand factor (VWF). Due to the large heterogeneity of VWF
      defects and to the external variables influencing VWF levels in the circulation,
      VWD diagnosis can be difficult, especially in relatively mild forms. Three
      criteria should be always satisfied for a correct VWD diagnosis: (1) a positive
      bleeding history since childhood; (2) reduced levels of VWF activity in plasma;
      and (3) autosomal dominant or recessive inheritance patterns within the family
      (in most cases). According to clinical prospective studies, a bleeding history in
      VWD patients should be derived from a detailed questionnaire, with calculated
      bleeding scores. The ristocetin cofactor activity is the most useful test for VWD
      screening in the general population because it reproduces in vitro the first VWF
      interactions with its platelet receptor; however other assays are required to
      identify and classify VWD types. The current classification (types 1, 2A, 2B, 2M,
      2N, and 3) is important to understand the basic mechanisms of VWF defects, to
      determine the risk of bleeding, and to select the best therapeutic approach.
      Molecular screening can be important to confirm phenotypic diagnosis for tracking
      VWF defects within families. Compared with hemophilia, most VWD patients show
      relatively mild bleeding symptoms. Therefore, prenatal diagnosis is required only
      for women already known to be carriers of VWD type 3. No spontaneous bleedings
      usually occur at birth in severe type 3 VWD. Neonatal diagnosis of VWD should
      always be compared with other affected members within the same family. Given that
      young children with VWD type 3 might carry deletions of VWF gene that predispose
      to the alloantibodies to VWF, every new child with VWD type 3 should be
      investigated intensively for VWF gene deletions before starting extensive therapy
      with exogenous VWF concentrates.

PMID- 16977567
TI  - Laboratory monitoring of therapy in von Willebrand disease: efficacy of the PFA
      100 and von Willebrand factor:collagen-binding activity as coupled strategies.
AB  - Clinical management of von Willebrand disease (or von Willebrand disorder [vWD])
      often involves factor replacement or desmopressin acetate (DDAVP) therapy to
      control (potential) bleeding. Laboratory monitoring involves testing patient
      samples prior to therapy and at discreet time points after therapy. Classical
      testing generally comprises assays for factor VIII:coagulant activity, von
      Willebrand factor (vWF):antigen and vWF:ristocetin cofactor activity. The PFA-100
      (platelet function analyser) is a relatively new tool for the investigation of
      primary hemostasis, and studies have shown its potential utility in identifying
      both vWD and platelet disorders, and in monitoring DDAVP therapy in these
      patients. However, the PFA-100 has limited utility in monitoring factor
      replacement therapy. The collagen-binding activity (vWF:CB) assay is a relatively
      new functional vWF assay and studies have also shown its utility in identifying
      vWD, and in monitoring both DDAVP and factor replacement therapy in these
      patients. This review assesses the laboratory monitoring of therapy for vWD with
      a special focus on the combined potential utility of the PFA-100 and a vWF:CB
      assay sensitive for the presence or absence of large vWF multimers. This review
      should be of value to both hemostasis scientists and clinical specialists.

PMID- 16977568
TI  - Immune-mediated etiology of acquired von Willebrand syndrome in systemic lupus
      erythematosus and in benign monoclonal gammopathy: therapeutic implications.
AB  - The most common nonimmune etiology of acquired von Willebrand syndrome (AvWS)
      includes hypothyroidism, Wilms' tumor, thrombocythemia, or congenital heart
      defects, and the use of various drugs. AvWS type 1 in patients with
      hypothyroidism is due to decreased Willebrand factor (vWF) synthesis and is
      reversible by treatment with thyroxin. AvWS type 1 or 3 in children with Wilms'
      tumor disappears after successful chemotherapy or tumor resection but the
      mechanism of the vWF deficiency is unknown. The AvWS type 2 in patients with
      thrombocythemia of various myeloproliferative disorders is caused by increased
      proteolysis of large vWF multimers at increasing platelet counts to above 1000 x
      10 (9)/L. Reduction of platelet counts to normal results in correction of the vWF
      parameters together with disappearance of the bleeding tendency. Type 2-like AvWS
      in children with congenital heart valve defects is caused by shear stress-induced
      proteolysis of large vWF multimers and is reversible after surgical correction.
      AvWS associated with the use of drugs disappears after discontinuation of the
      causative agent. Immune-mediated AvWS is associated with either systemic lupus
      erythematosus (SLE) or immunoglobulin G (IgG) benign monoclonal gammopathy (BMG),
      and usually shows a type 2 vWF deficiency. Using a simple enzyme-linked
      immunosorbent assay, an IgG antibody against vWF is detectable in AvWS associated
      with SLE and IgG BMG. The IgG-autoantibody-factor (F) vWF/VIII complex is rapidly
      cleared from the circulation, which explains the combined FVIII:coagulant
      activity (C) and vWF deficiency and the poor responses of FVIII:C and vWF
      parameters to intravenous desmopressin acetate and vWF/FVIII concentrates. A
      transient correction of both FVIII:C and vWF parameters to normal for a few weeks
      after high-dose intravenous immunoglobulin is seen in AvWS associated with SLE
      and IgG BMG. AvWS associated with SLE uniformly shows a curative response to
      corticosteroids. AvWS associated with IgG BMG does not respond to
      corticosteroids, immune suppression, or chemotherapy. AvWS associated with IgM
      BMG is rare and does not respond to any conventional treatment.

PMID- 16977569
TI  - The paradox of platelet activation and impaired function: platelet-von Willebrand
      factor interactions, and the etiology of thrombotic and hemorrhagic
      manifestations in essential thrombocythemia and polycythemia vera.
AB  - Patients with essential thrombocythemia (ET) and polycythemia vera (PV),
      complicated by microvascular ischemic or thrombotic events, have shortened
      platelet survival, increased beta-thromboglobulin, platelet factor 4, and
      thrombomodulin levels, and increased urinary thromboxane B2 excretion. These are
      all reversible by inhibition of platelet cyclooxygenase 1 with aspirin, and are
      therefore indicative of platelet activation and platelet-mediated thrombotic
      processes. The thrombotic tendency persists as long as platelet counts are above
      the upper limit of normal (400 x 10 (9)/L). Despite strong evidence of in vivo
      platelet activation, the ex vivo platelet function tests are impaired. Platelet
      dysfunction in ET and PV typically is characterized by a missing second-wave
      adrenaline aggregation, an increased adenosine diphosphate aggregation threshold,
      and reduced secretion products, but a normal arachidonic acid or collagen-induced
      aggregation. The proposed concept is that platelets in thrombocythemia (ET and
      PV) are hypersensitive. Due to the existing high shear stress in the
      microvasculature (end-arterial circulation), platelets spontaneously activate,
      secrete their products, form aggregates mediated by von Willebrand factor (vWF)
      that transiently plug the microcirculation, deaggregate, and then recirculate as
      exhausted defective platelets with secondary storage pool disease on ex vivo
      analysis. At increasing platelet counts from below to above 1000 x 10 (9)/L, the
      thrombotic condition changes into an overt spontaneous bleeding tendency as a
      result of a functional vWF deficiency that is caused by proteolysis of large vWF
      multimers. This is consistent with acquired type 2 von Willebrand syndrome
      (AvWS). AvWS is reversible by reduction of the platelet count to normal. The
      acquired JAK2 V617F gain of function mutation is the cause of trilinear
      myeloproliferative disease with the sequential occurrence of ET and PV.
      Heterozygous JAK2 V617F mutation with slightly increased kinase activity is
      enough for the induction of spontaneous megakaryopoiesis and erythropoiesis, and
      an increase of hypersensitive platelets is the cause of aspirin-sensitive,
      platelet-mediated microvascular ischemic and thrombotic complications in ET and
      early PV mimicking ET. Homozygous JAK2 mutation with pronounced increase of
      kinase activity is associated with pronounced trilinear megakaryocyte, erythroid,
      and granulocytic myeloproliferation, with the most frequent clinical picture of
      classical PV complicated by major thrombosis, in addition to the platelet
      mediated microvascular thrombotic syndrome of thrombocythemia.

PMID- 16977570
TI  - Women and von Willebrand disease: controversies in diagnosis and management.
AB  - von Willebrand disease (vWD) is the commonest bleeding disorder in women. More
      than 70% of women with vWD suffer from menorrhagia and half of them suffer from
      dysmenorrhea. There is also the risk of hemorrhage with ovulation and mid-cycle
      pain. These have a significant effect on all aspects of quality of life. vWD also
      can be the underlying cause of menorrhagia in a small but significant proportion
      of women. There are still several unanswered issues in the diagnosis and
      management of menorrhagia in these women. There is no consensus whether testing
      for vWD should be part of the routine investigations in menorrhagia. Diagnosis of
      vWD is difficult. There are intraindividual variations in von Willebrand factor
      and factor VIII levels influenced by age, race, and blood group. This is further
      complicated in women because of the fluctuation of these factor levels during the
      menstrual cycle and possibly with hormonal therapy. The diagnosis of menorrhagia
      is also difficult due to the lack of a simple objective tool for the assessment
      of menstrual blood loss. In vWD, the treatment of menorrhagia is usually medical,
      but there is lack of prospective data on the efficacy of commonly used medical
      therapies in these women. The levonorgestrel intrauterine system, Mirena, is
      effective and should be considered prior to surgical management. Surgical
      interventions may be required in patients unresponsive to medical treatments.
      These procedures can be complicated by hemorrhage in these women. A
      multidisciplinary approach in the management of these women is essential in
      ensuring an optimal outcome. Multicenter clinical trials are required to answer
      the controversial issues in the management of women with vWD.

PMID- 16977571
TI  - Management of inherited von Willebrand disease in 2006.
AB  - The aim of treatment of von Willebrand disease (VWD) is to correct the dual
      defect of hemostasis (i.e., the abnormal platelet adhesion due to reduced and/or
      dysfunctional von Willebrand factor [VWF] and the abnormal coagulation expressed
      by low levels of factor [F] VIII). Desmopressin acetate (DDAVP) is the treatment
      of choice for type 1 VWD because it can induce release of normal VWF from
      cellular compartments. Prospective studies on biological response versus clinical
      efficacy of DDAVP in VWD types 1 and 2 are in progress to explore its benefits
      and limits as a therapeutic option. In type 3 and in severe forms of type 1 and 2
      VWD, DDAVP is not effective, and for these patients plasma virally inactivated
      concentrates containing VWF and FVIII are the mainstay of treatment. Several
      intermediate- and high-purity VWF/FVIII concentrates are available and have been
      shown to be effective in clinical practice (bleeding and surgery). New VWF
      products almost devoid of FVIII are now under evaluation in clinical practice.
      Although thrombotic events are rare in VWD patients receiving repeated infusions
      of concentrates, there is some concern that sustained high FVIII levels may
      increase risk of postoperative venous thromboembolism. Dosage and timing of
      VWF/FVIII administrations should be planned to keep the FVIII level between 50
      and 150 IU/dL. Appropriate dosage and timing in repeated infusions are also very
      important in patients exposed to secondary long-term prophylaxis for recurrent
      bleedings.

PMID- 16977572
TI  - Prophylaxis and treatment of bleeding complications in von Willebrand disease
      type 3.
AB  - Treatment of type 3 von Willebrand disease (vWD) relies on infusion with plasma
      derived factor concentrates containing von Willebrand factor (vWF). Patients with
      types 1 and 2 vWD who do not respond satisfactorily after receiving desmopressin
      need treatment with concentrates. The rationale for long-term prophylaxis in vWD
      is obvious: prophylaxis has been successfully used in hemophilia, and joint
      hemorrhages with development of hemophilic arthropathy can occur, especially in
      type 3 vWD. In Sweden, prophylaxis for vWD began during the 1960s, and we now
      have experience from a cohort of 37 patients treated for a median of 11 years
      (range, 2 to 45 years). The majority of subjects (n = 28) have type 3 vWD. The
      mean dose used for treatment is 24 units factor VIII/kg body weight given one to
      three times weekly. Indications for prophylaxis have included joint bleeds,
      bleeds from nose and mouth, menorrhagia and gastrointestinal bleeds. The annual
      number of bleeds has decreased dramatically following onset of prophylaxis. We
      conclude that long-term prophylactic treatment of vWD is warranted in the
      majority of cases with type 3 and in some cases, depending on the clinical
      phenotype, for patients with other subtypes. Additional studies are ongoing in an
      international effort, the von Willebrand Disease Prophylaxis Network.

PMID- 16977573
TI  - Comparative analysis and classification of von Willebrand factor/factor VIII
      concentrates: impact on treatment of patients with von Willebrand disease.
AB  - von Willebrand disease (vWD) is a bleeding disorder that results from defects in
      the quality or quantity of von Willebrand factor (vWF), a glycoprotein essential
      for normal thrombus formation. vWF circulates in plasma as multimers in sizes
      ranging up to 20,000 kd. The high molecular weight vWF (HMWvWF) multimers are
      most essential for primary hemostasis, whereas the lower molecular weight
      multimers are less functionally active. For many patients, the treatment of
      choice is factor replacement with a vWF/FVIII concentrate, preferably one with a
      high content of HMWvWF multimers. Given that the commercially available vWF/FVIII
      concentrates seem to differ substantially in their biochemical properties as well
      as in their clinical efficacy, we did a comparative study with 12 vWF/FVIII
      concentrates to investigate content and activities of FVIII and vWF, as well as
      the content of HMWvWF multimers. The content of HMWvWF multimers varied
      considerably among the 12 concentrates. The specific vWF activities, as assessed
      by ristocetin cofactor activity (vWF:RCo) and collagen-binding activity (vWF:CB),
      correlated well with the HMWvWF content of the products. Of the products tested,
      Haemate P/Humate-P had the highest content of HMWvWF multimers (with a multimer
      pattern closest to that of normal human plasma), the highest specific vWF
      activities, and the highest values of vWF:RCo and vWF:CB per unit of
      FVIII:coagulant (C). The goal of bleeding prophylaxis and treatment in type 2,
      severe type 1, and type 3 vWD patients is to normalize vWF activities (vWF:RCo
      and vWF:CB) and FVIII:C preferentially by vWF/FVIII concentrates containing the
      high vWF multimers and a high vWF:RCo/FVIII ratio to achieve normal primary and
      secondary hemostasis. Based on the present study of a comparative analysis of
      currently available vWF/FVIII concentrates, a classification of vWF/FVIII
      products is proposed.

PMID- 16977574
TI  - Guidelines for the evaluation of intravenous desmopressin and von Willebrand
      factor/factor VIII concentrate in the treatment and prophylaxis of bleedings in
      von Willebrand disease types 1, 2, and 3.
AB  - The current standard for the diagnosis and management of patients with congenital
      von Willebrand disease (vWD) includes bleeding times (BTs), PFA-100 closure time
      (PFA-CT), factor (F) VIII:coagulant activity (C), vWF:antigen (Ag),
      vWF:ristocetin cofactor activity (RCo), a sensitive vWF:collagen-binding activity
      (CB), ristocetin-induced platelet aggregation (RIPA), analysis of vWF multimers
      in low- and high-resolution agarose gels, and the response to desmopressin.
      Guidelines and recommendations for prophylaxis and treatment of bleedings in vWD
      patients with vWF/FVIII concentrates should be derived from analysis of the
      content of these concentrates and from pharmacokinetic studies in different types
      of vWD patients with severe type 1, 2, or 3 vWD. The vWF/FVIII concentrates
      should be characterized by labeling with FVIII:C, vWF:RCo, vWF:CB, and vWF
      multimeric pattern, which will determine their predicted efficacy and safety in
      prospective management studies. Because the bleeding tendency is moderate in type
      2 and severe in type 3 vWD, and because the FVIII:C levels are subnormal in type
      2 and very low in type 3 vWD patients, new guidelines using vWF:RCo unit dosing
      for the prophylaxis and treatment of bleeding episodes are proposed. Such
      guidelines should be stratified for the severity of bleeding, the type of surgery
      (either minor or major), and also for the severity and type of vWD (i.e., either
      type 2 or 3 vWD).

PMID- 16977575
TI  - The use of aspirin and clinical implications in essential thrombocythemia.

PMID- 16977576
TI  - Cellular proliferation, differentiation and apoptosis in polyether-polyurethane
      sponge implant model in mice.
AB  - The integration of implanted material to host organism requires spatial and
      temporal organization of several cellular processes, such as proliferation,
      differentiation and apoptosis. Despite the clinical relevance of these processes,
      there is little information regarding the sequence of such events in synthetic
      matrices. Here, we present a combination of techniques used to characterize the
      fibrovascular response in subcutaneous polyether-polyurethane sponge implants in
      mice at days 4, 7, 10 and 14 postimplantation. The AgNOR technique was modified
      and used as a surrogate marker for proliferating and activated cells invading the
      implant. The number of AgNOR-stained cells increased progressively from day 4
      (606+/-76) to day 14 (2146+/-71) postimplantation. The number of TUNEL-positive
      (apoptotic index) cells also increased progressively from day 4 (459+/-40) to day
      14 (1157+/-119) postimplantation. However, the ratio of TUNEL
      labeled/proliferating cells had its highest peak in the early phase of the
      process remaining stable until day 14. Using Picrosirius staining it was shown
      that thin collagen increased from day 4, peaking at day 10 and falling markedly
      at day 14, whereas dense collagen increased progressively during the whole
      period. These experiments hold potential to investigate not only distinct phases
      of tissue repair induced by synthetic matrices but also to study underlying
      mechanisms involved.

PMID- 16977577
TI  - Chronic hypoxia alters calbindin D-28k immunoreactivity in lingual and laryngeal
      taste buds in the rat.
AB  - The distribution and abundance of the calcium binding protein, calbindin D-28k
      (CB) immunoreactivity in the taste buds of the circumvallate papillae and larynx
      were compared between normoxic and chronically hypoxic rats (10% O2 for 8 weeks).
      In the normoxic rats, CB immunoreactivity was observed in some cells and fibers
      of the intragemmal region of the taste buds in the circumvallate papillae. In
      contrast, in the subgemmal region of the laryngeal taste buds, fibers but not
      cells were immunoreactive for CB. In chronically hypoxic rats, CB immunoreactive
      cells and fibers in the taste buds were decreased in the circumvallate papillae.
      In the laryngeal taste buds, the density of the subgemmal CB immunoreactive
      fibers in chronically hypoxic rats was greater than in normoxic rats. It is
      considered that function of the laryngeal taste buds is different from that of
      the lingual taste buds, so that laryngeal taste buds may be involved in
      chemosensation other than taste. The altered density of CB immunoreactive cells
      and fibers in the lingual and laryngeal taste buds is a predominant feature of
      hypoxic adaptation, and chronic hypoxic exposure might change the chemical
      sensitivity of the circumvallate papillae and larynx through the regulation of
      intracellular Ca2+.

PMID- 16977578
TI  - Bone allograft non-union is related to excessive osteoclastic bone resorption: a
      sheep model study.
AB  - Using a sheep femoral allograft model we have investigated the cellular and
      molecular mechanisms associated with non-union of bone allografts.
      Histomorphometric analysis revealed that allograft non-unions featured both
      marked increases in osteoclast (OC) numbers and total eroded bone surface as
      compared to allografts which had undergone direct union. Three distinct cellular
      layers lying adjacent to the allograft bone surface were identified in all non
      union cases. The outer or fibroblastic layer contained an abundance of
      fibroblasts and connective tissue. Circumscribing this layer was a band of
      synovial-like cells consisting mainly of large spindle-shaped mononuclear cells
      mixed with scattered round-shaped mononuclear cells. The third layer, which was
      directly juxtaposed to the allograft bone surface, consisted predominantly of
      multinuclear OCs which were positively identified by calcitonin receptor
      immunohistochemistry. Interestingly, in-situ hybridisation revealed that
      surrounding synovial-like cells in non-union allografts, expressed abundant gene
      transcripts for receptor activator NF-kappaB ligand (RANKL), a membrane bound
      factor critical for both the induction of OC activity and osteoclastogenesis. We
      propose that excessive bone resorption by host OCs contributes, at least
      partially, to the failure of bone allografts. The production of RANKL by synovial
      like fibroblasts may be the driving force responsible for the elevated generation
      and activation of OCs. Based on such evidence novel therapeutic strategies for
      the treatment of non-union bone allografts using anti-bone resorbing agents may
      be devised.

PMID- 16977579
TI  - Increasing expression of fascin in renal cell carcinoma associated with
      clinicopathological parameters of aggressiveness.
AB  - AIM: To determine whether higher expression of fascin, an actin-bundling protein
      associated with motility, in conventional renal cell carcinoma (RCC) is
      associated with more advanced stages of the disease. METHODS: Immunohistochemical
      analysis of fascin expression was performed in tissue microarrays of 108 RCCs
      including 55 clear cell RCCs (CRCCs), 39 CRCCs with granular cell differentiation
      (GRCCs), 8 CRCCs with sarcomatoid differentiation (SRCCs) and 6 metastatic RCCs.
      RESULTS: The expression of fascin was undetectable in normal renal tubules of all
      control cases. However, among the 108 RCC cases, fascin immunoreactivity was seen
      on the cell membrane and cytoplasm. The average immunostaining score for fascin
      was 128/400 in grade I, 170/400 in grade II, 207/400 in grade III, and 323/400 in
      grade IV RCC. The average immunostaining score of fascin was 187/400 for stage
      T1, 205/400 for stage T2, 288/400 for stage T3, and 355/400 for stage T4 cases of
      RCCs. Higher fascin scores in RCC were significantly correlated with higher T and
      N stages and nuclear grade. In addition, the fascin scores in GRCC (368+/-19) and
      SRCC (263+/-21) were significantly higher than in CRCC (95+/-18). CONCLUSIONS:
      Our findings demonstrate for the first time that increased expression of fascin
      is associated with clinicopathological parameters of aggressiveness in patients
      with RCC. Fascin may be a novel biomarker for diagnosis and treatment of RCC.

PMID- 16977580
TI  - Detection of platelet-derived growth factor-alpha (PDGF-A) protein in cells of
      Leydig lineage in the postnatal rat testis.
AB  - Platelet-derived growth factor-A (PDGF-A) is a locally produced growth factor in
      the rat testis secreted by both Sertoli cells and Leydig cells. It has been
      suggested that PDGF-A may be involved in modulation of testosterone production
      and may be essential to Leydig cell differentiation, however it is not known at
      what stage of differentiation PDGF-A begins to be expressed in the cells of
      Leydig lineage in the postnatal rat testis. Therefore, the objectives of this
      research were to determine at what postnatal age and in which cell type is PDGF-A
      first expressed in cells of the adult Leydig cell lineage, and does PDGF-A
      expression coincide with expression of 3beta-hydroxysteroid dehydrogenase (3beta
      HSD), an indicator of steroid hormone synthesis. Male Sprague Dawley rats of
      postnatal day 1, 7, 9-14, 21, 28, 40, 60, and 90 were used (n=6). Animals were
      euthanized and their testicles removed, fixed in Bouin's solution, embedded in
      paraffin, and 5 micrometers sections were prepared. Immunolocalization of PDGF-A
      and 3beta-HSD was carried out using a peroxidase-streptavidin-biotin method. PDGF
      A was first detected in cells of the Leydig cell lineage at postnatal day 10 in
      progenitor cells, which were surrounding the seminiferous tubules (peritubular).
      These cells were confirmed to be the progenitor cells and not the mesenchymal or
      any other spindle-shaped cells in the testis interstitium by immunolocalization
      of 3beta-HSD and PDGF-A in the cells in adjacent sections of testis tissue from
      rats of postnatal days 10-14. After postnatal day 10, PDGF-A was continued to be
      expressed in subsequent cells of the Leydig lineage through day 90 (adult),
      however, was not present in peritubular mesenchymal precursor cells of the Leydig
      cell lineage or any other spindle-shaped cells in the testis interstitium at any
      tested age. These results revealed that PDGF-A first appears in Leydig progenitor
      cells in the postnatal rat testis at the onset of mesenchymal cell
      differentiation into progenitor cells at postnatal day 10 and suggest that a
      functional role(s) of PDGF-A in postnatally differentiated Leydig cells in the
      rat testis is established at the time of the onset of postnatal Leydig stem cell
      differentiation. It is suggested that the significance of the first expression of
      PDGF-A in the Leydig progenitor cells may be associated with inducing cell
      proliferation and migration of this cell away from the peritubular region during
      Leydig cell differentiation.

PMID- 16977581
TI  - The distribution of myofibroblasts and CD34-positive stromal cells in normal
      renal pelvis and ureter and their cancers.
AB  - In this article, we examined the distribution of myofibroblasts and CD34-positive
      stromal cells in normal renal pelvis and ureter and their cancers using
      immunohistochemistry. Eighteen tumors and normal tissues apart from the main
      tumor were examined. In the wall of normal renal pelvis and ureter, no
      myofibroblasts were observed through all layers, but CD34-positive stromal cells
      were observed in the deep area of lamina propria, muscular layer and adventitia.
      In the stroma of renal pelvic and ureteral cancers, myofibroblasts were
      distributed in fifteen tumors and were absent in three tumors. All three tumors
      containing no myofibroblasts in the stroma were non-invasive type and all
      invasive cancers contained myofibroblasts in the stroma. CD34-positive stromal
      cells were consistently absent in the stroma of cancers, irrespective of the
      invasiveness. Finally, myofibroblasts are major stromal components in renal
      pelvic and ureteral cancers, particularly in invasive cancers, and CD34-positive
      stromal cells are consistently absent or lost in the stroma of their cancers.
      These findings suggest that the invasion of renal pelvic and ureteral cancers may
      cause the phenotypic change of stromal cells.

PMID- 16977582
TI  - Morphogenesis of rat experimental pulmonary emphysema induced by intratracheally
      administered papain: changes in elastic fibres.
AB  - The ultrastructural changes of elastic fibres in emphysematous lungs have been
      studied in men, but few works exist on this topic in experimental emphysematous
      animals. In this paper, the morphogenesis of emphysema and alterations of the
      elastic fibres produced by the instillation of papain are described by light and
      electron microscopy. Wistar rats were instilled through the trachea with papain
      at a rate of 3 mg/100 g animal weight. The animals were sacrificed 12 h, 3 days,
      10 days and 60 days after enzyme instillation. The "Mean Linear Intercept" (MLI),
      the "Number of fenestrations/respiratory units" (NF) the "Number of macrophages
      per mm of alveolar wall" (NM) and the "Number of respiratory unit/mm2" (RU), both
      in the control and experimental groups were studied. Two months after treatment,
      the experimental group showed a strong increase in the MLI (p<0.001) and NF
      (p<0.001), and a diminished number of RU (p<0.05) compared with the control
      group. Partial correlation analysis showed a positive correlation only between
      MLI and NF. Twelve hours after papain instillation an inflammatory response was
      observed, the elastic fibres were ruptured, while the microfibrilar component
      remained. New formations of eulanin elastic fibres were observed three days post
      papain instillation. After ten days the interalveolar oedema had disappeared and
      the elastic fibres were of normal morphology although irregular groups of strips
      of elastic fibres were evident. A mixed pattern of panlobular, centrilobular and
      normal lung zones were observed. Two months after papain instillation abundant
      accumulations of elastic fibres of irregular outline were observed associated to
      collagen fibres. In conclusion, the morphometric parameters studied showed a
      significant progression of the emphysema. The strong correlation between NF and
      MLI suggested that papain-induced emphysema is principally caused by breaches of
      the alveolar walls. The results seem to point to a very abnormal remodelling
      process associated with elastic fibre regeneration, although there were no signs
      of destruction of these new fibres formed in emphysematous rat lung induced by
      papain.

PMID- 16977583
TI  - Caspase-3 and caspase-6 in ductal breast carcinoma: a descriptive study.
AB  - Caspases are the main point in the apoptotic process. We have collected some
      information from 210 cases of Ductal breast cancer (pT1 - pT2) such as tumour
      size, histological differentiation degree, lymph node status and tumor necrosis
      in the infiltrating component and we have evaluated the number of apoptotic cells
      or bodies by TUNEL technique as well as immunohistochemical studies to evaluate
      the expression of caspase 3 and caspase 6, and proliferation index. Our results
      show that lymph node status and cell atypism are independent prognostic factors
      for recurrence and mortality and only tumour size is an independent prognostic
      factor for recurrence. However, the apoptotic index and the immunohistochemical
      expression of caspases and cell proliferation index have not turned out to be
      independent prognostic factors neither for recurrence nor mortality. These
      results show that classic prognostic factors known until now are the most
      important factors to predict the evolution of the illness.

PMID- 16977584
TI  - Fetal ocular movements and retinal cell differentiation: analysis employing DNA
      microarrays.
AB  - As developmental biologists we study the role of fetal movements in providing
      continuity between prenatal and postnatal life. There are two major categories of
      fetal motility. The first category consists of movements that have an obvious
      effect on the survival or development of the fetus (e.g., changes of position,
      sucking and swallowing). The second category consists of fetal movements that
      anticipate postnatal functions. For example, fetal ocular movements (FOMs)
      predict postnatal eye function (e.g., motion vision) of the newborn and therefore
      represent an important indicator of fetal health. However, while the clinical
      significance of fetal motility is obvious, its biological significance is
      elusive. We propose to use retina of genetically modified mouse embryos to study
      the biological role of FOMs in the genesis of cell diversity and organ functional
      maturation. Our results have already demonstrated the importance of fetal eye
      motility in the differentiation of cholinergic amacrine cells (CACs) in the
      retina (Kablar, 2003). Apparently, these cells are sensitive to motion and also
      responsible for motion vision. In the current report, we suggest employing the
      unique opportunity provided by the mouse Myf5-/-:MyoD-/- knock-outs that lack
      skeletal musculature and FOMs, microarray analysis and the follow-up experiments
      to identify a group of candidate genes that are essential for the molecular
      regulation of CAC differentiation and in turn for the functional maturation of
      the visual system towards its ability to perform motion vision. Finally, the
      molecules identified via this approach may be important in the mechanochemical
      signal transduction pathways employed during the process of conversion of a
      mechanical stimulus into an instruction understandable by the developing retinal
      neurons and glia cells.

PMID- 16977585
TI  - Ectopeptidases in tumour biology: a review.
AB  - Cell membrane-bound proteolytic enzymes (ectopeptidases) are integral membrane
      proteins, orientated asymmetrically with the catalytic site exposed to the
      extracellular surface, which enables a versatile range of physiological and
      pathological functions. Ectopeptidases may regulate the release of many growth
      factors and their receptors into the circulation, as well as activating or
      inactivating circulating signalling molecules, thereby regulating the
      availability of ligands for the corresponding receptors. Additionally, many of
      these ectopeptidases have functions not limited to proteolysis, but are able in
      themselves to function as receptors, transducing intracellular signals. A
      versatile range of functions, such as the modulation of cell-signalling, matrix
      degradation, cell adhesion and migration, which are particularly important for
      tumour cell growth and dissemination, are attributed largely to the
      ectopeptidases. Even a minor disruption in the normal proteolytic equilibrium can
      influence tumor progression, and a range of ectopeptidases, including neutral
      endopeptidase 24.11, aminopeptidase N, dipeptidyl peptidase IV, angiotensin
      converting enzyme, and the disintegrin-metalloproteinases, have been shown to be
      involved in tumour development and metastasis. The ability to degrade and
      inactivate peptide hormones and growth factors, with the resultant modulation of
      the tumour-host interface, may play an important role in the pathogenesis,
      development or progression of a range of cancers, and the extracellular
      orientation of the ectopeptidases makes them particularly accessible, and
      therefore interesting, with regard to therapeutical applications.

PMID- 16977586
TI  - Natural IgM antibodies: from parias to parvenus.
AB  - Over the years, natural IgM antibodies were considered as the parias among the
      immune competent molecules. Their characteristic properties, like low affinity,
      cross-reactivity and pentameric structure, were assessed as difficult and
      nebulous. Today, mainly based on the persistent work of a few researchers and the
      key discoveries on innate immunity, natural IgM antibodies are "back on stage".
      Their important role in the immune response against invasive particles, modified
      self-components and altered cells is accepted. All the so far negatively judged
      features have to be seen in a different light, e.g. low affinity seems to be good
      for function and does not exclude specificity, cross-reactivity is no longer
      judged as unspecific, but instead as a very economic way of immune recognition
      and the pentameric structure is important for binding capacity and functional
      activities. In addition, with the use of natural IgM antibodies, a new field of
      tumour-specific targets has been encountered, the carbo-neo-epitopes, which are
      commonly found on post-transscriptionally modified membrane receptors. Having
      understood the typical features of natural IgM antibodies, their renaissance
      opens a new area of cancer therapeutics and diagnostics.

PMID- 16977587
TI  - Myelofibrosis in chronic myeloproliferative disorders--dynamics and clinical
      impact.
AB  - In chronic myeloproliferative disorders, presenting or evolving myelofibrosis
      (MF) is associated with significant morbidity and mortality. A systematically
      conducted evaluation of previous studies and data from our own material reveals a
      strikingly expressed heterogeneity of findings. Assessment of MF should be
      performed by a recently established semiquantitative scoring system regarding
      quantity and quality (reticulin versus collagen). It is important to
      differentiate between a fiber increase in bone marrow specimens and the clinical
      diagnosis that is explicitly based on extramedullary hematopoiesis (myeloid
      metaplasia). For this reason, prodromal stages of (reticulin) fibrosis are
      overlooked by the clinicians. Up to 30% of patients with chronic myelogenous
      leukemia show a minimal to advanced MF that is significantly associated not only
      with corresponding clinical parameters but more importantly with prognosis. In
      polycythemia vera about 20% of patients may display some degree of reticulin
      fibrosis at diagnosis, depending on stage of the disease. Transformation into
      (collagen) MF after more than 10 years is accompanied by clinical signs of
      myeloid metaplasia (spent phase). Essential thrombocythemia (ET) is characterised
      by the absence of increased reticulin at onset and an insignificant progression
      into MF, provided diagnosis is performed by the WHO criteria. Discrimination of
      prefibrotic and early stages of chronic idiopathic myelofibrosis (CIMF) from ET
      is relevant, especially concerning the rate and time usually required for the
      development of MF with myeloid metaplasia (full-blown CIMF). In conclusion, more
      elaborate evaluations including standardized grading of MF is warranted by
      regarding bone marrow biopsy specimens in association with clinical parameters
      including follow-up examinations.

PMID- 16977588
TI  - Separation and quantification of inulin in selected artichoke (Cynara scolymus
      L.) cultivars and dandelion (Taraxacum officinale WEB. ex WIGG.) roots by high
      performance anion exchange chromatography with pulsed amperometric detection.
AB  - The profile of fructooligosaccharides and fructopolysaccharides in artichoke
      heads and dandelion roots was investigated. For this purpose, a suitable method
      for high-performance anion exchange chromatography with pulsed amperometic
      detection was developed. The separation of monomers, oligomers and polymers up to
      a chain length of 79 sugar residues was achieved in one single run. Glucose,
      fructose, sucrose and individual fructooligosaccharides (kestose, nystose,
      fructofuranosylnystose) were quantified in six different artichoke cultivars and
      in dandelion roots. The contents ranged from 12.9 g/kg DM to 71.7 g/kg DM for
      glucose, from 15.8 g/kg DM to 67.2 g/kg DM for fructose, and from 16.8 g/kg DM to
      55.2 g/kg DM for sucrose in the artichoke heads. Kestose was the predominant
      fructooligosaccharide, followed by nystose and fructofuranosylnystose. In four
      cultivars fructofuranosylnystose was only detectable in traces and reached its
      maximum value of 3.6 g/kg DM in the cultivar Le Castel. Furthermore, an average
      degree of polymerization of 5.3 to 16.7 was calculated for the individual
      artichoke cultivars, which is noticeably lower than hitherto reported. In
      contrast, the contents of kestose, nystose and fructofuranosylnystose in
      dandelion root exceeded that of artichoke, reflecting the short chain
      characteristic of the inulin, which was confirmed by chromatographic analysis.

PMID- 16977589
TI  - Validated HPLC method for determination of carboxylic acid metabolite of
      clopidogrel in human plasma and its application to a pharmacokinetic study.
AB  - A new, simple, and reproducible method for determination of carboxylic acid
      metabolite of clopidogrel in human plasma has been developed. After liquid-liquid
      extraction in acidic medium with chloroform, samples were quantified on a Nova
      pak C(8), 5 microm column using a mixture of 30 mM K(2)HPO(4)-THF-acetonitrile
      (pH = 3, 79:2:19, v/v/v) as mobile phase with UV detection at 220 nm. The flow
      rate was set at 0.9 mL/min. Ticlopidine was used as internal standard and the
      total run time of analysis was about 12 min. The method was linear over the range
      of 0.2-10 microg/mL of clopidogrel metabolite in plasma (r(2) > 0.999). The
      within-day and between-day precision values were in the range 1.0-4.8%. The limit
      of quantification of the method was 0.2 microg/mL. The method was successfully
      used to study the pharmacokinetics of clopidogrel in healthy volunteers.

PMID- 16977590
TI  - Simultaneous determination of YM928, a novel noncompetitive AMPA receptor
      antagonist, and its demethylated metabolite in rat, dog and monkey plasma by high
      performance liquid chromatography with ultraviolet detection.
AB  - A specific HPLC method for the simultaneous determination of YM928, a novel
      noncompetitive AMPA receptor antagonist, and its demethylated metabolite (YM
      58875) in rat, dog and monkey plasma was developed and validated. The method
      utilized multiple-step liquid-liquid extraction followed by a reversed-phase HPLC
      with UV detection at 275 nm. No interfering peaks were observed at the retention
      times of YM928, YM-58875 or internal standard. The validated quantitation range
      was 5-5000 ng/mL for both YM928 and YM-58875 when 1 mL of the plasma sample was
      used. The intra- and inter-day precision was less than 5.3 and 2.5% for YM928,
      and 3.7 and 2.3% for YM-58875, respectively. The intra- and inter-day accuracies
      were -8.7-5.3% and 0.7-1.9% for YM928, and -10.0-6.1% and 1.3-3.4% for YM-58875,
      respectively. The mean recoveries in the extraction process were 52.7-62.8%. The
      utility of this analytical method was demonstrated by the investigation of the
      pharmacokinetics of the unchanged drug and its metabolite in preclinical studies.

PMID- 16977591
TI  - Determination of substance P in rat spinal cord by high-performance liquid
      chromatography electrospray quadrupole ion trap mass spectrometry.
AB  - Substance P is a neuropeptide that belongs to the tachykinin neuropeptide family.
      It is an 11-amino acid polypeptide with the amino acid sequence: Arg-Pro-Lys-Pro
      Gln-Gln-Phe-Phe-Gly-Leu-Met. It is synthesized as a larger protein and then
      enzymatically converted into the active undecapeptide. Substance P is widely
      distributed in the central and peripheral nervous systems. In the central nervous
      system, substance P participates in various behavioral responses and in
      regulating neuronal survival and degeneration. In the spinal cord, substance P
      participates in neurotransmission of pain and modulates autonomic reflexes. A
      rapid and selective method was developed for the determination of substance P
      concentration in rat spinal cord. The method consisted of a tissue
      homogenization, dilution, centrifugation and analysis by full-scan liquid
      chromatography electrospray quadrupole ion trap mass spectrometry (LC-ESI-QIT).
      The separation was achieved using a 50 x 2.1 mm C(18) analytical column combined
      with a gradient mobile phase composed of methanol: 0.1% formic acid in water set
      at a flow rate of 0.2 mL/min. An analytical range of 10-500 pmol/g was tested to
      analyze rat spinal cord. The LOD observed was 10 fmol injected on column. The
      novel method met all requirements of specificity, sensitivity, linearity,
      precision, accuracy and stability. In conclusion, a rapid and sensitive LC
      ESI/MS/MS method was developed to identify and quantify substance P in rat spinal
      cord.

PMID- 16977593
TI  - Carcinogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in experimental models.
AB  - The contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a prototype
      compound of a whole class of halogenated aromatic hydrocarbons termed
      'dioxinlike' contaminants present in food, human tissue, mothers milk, and
      environmental samples. Among the various adverse effects caused by TCDD in animal
      experiments, its carcinogenic effects caused particular concern. In rodents, long
      term TCDD treatment leads to the development of tumors of the liver, thyroid,
      lung, skin, oral cavity and other sites. The occurrence of liver tumors mainly
      observed in female rats has been used as a basis for quantitative cancer risk
      assessment for TCDD. TCDD does not behave like a 'complete carcinogen', i. e. no
      DNA binding of the parent compound or metabolites thereof could be detected.
      However, enhanced oxidative damage of hepatic DNA was observed, probably
      resulting from a dramatic induction of cytochrome P450 enzymes, which are under
      the regulatory, transcriptional control of the TCDD-activated aryl hydrocarbon
      receptor. The marked enhancement of TCDD-related oxidative liver DNA damage in
      rats by estrogens warrants further mechanistic investigation. Furthermore, TCDD
      acts as a tumor promoter, i. e. it facilitates the growth of putative
      preneoplastic hepatic lesions after initiation with a complete carcinogen. The
      mechanisms underlying this effect may be related to altered intracellular
      signaling involving pronounced changes in the phosphorylation pattern of proteins
      regulating growth and apoptosis. These effects are thought to result in an
      enhanced survival of preneoplastic cells, some of which can undergo further steps
      on the way to malignancy. In summary, a better understanding of the mechanisms of
      the carcinogenicity of TCDD is mandatory to provide a rational basis for a better
      inter-species extrapolation. The final aim of these efforts is a more reliable
      risk assessment for the carcinogenic potency of the class of dioxinlike
      contaminants in humans.

PMID- 16977594
TI  - Comparison of chronic toxicity and carcinogenicity of 2,3,7,8-tetrachlorodibenzo
      p-dioxin (TCDD) in 2-year bioassays in female Sprague-Dawley rats.
AB  - The cancer bioassay for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) conducted by
      the Dow Chemical company in the mid 70s has been used extensively for conducting
      quantitative cancer risk assessments for human exposure to TCDD. More recently
      the National Toxicology Program (NTP) conducted a cancer bioassay of similar
      design as part of its evaluation of the dioxin toxic equivalency factor
      methodology. This report compares the design and the results of these two cancer
      bioassays. This comparison confirms, in most cases, previously published and
      widely used carcinogenic response characteristics with respect to dose, time
      course, organ selectivity, tumor type and maximum intensity of TCDD-induced
      carcinogenicity and toxicity in the Sprague-Dawley rat. Specifically, increases
      in the incidences of neoplasms were seen in both studies in the liver, lung and
      oral mucosa. The most notable difference was the significant increase in the
      incidence of cholangiocarcinoma of the liver seen in the NTP study but not in the
      Dow study. The experimental designs for the two studies are similar but some
      protocol parameters differed, such as vehicle, dosing schedule, diet and rat sub
      strain utilized. Differences in the shapes of the dose response curves for
      several neoplasms were noted between the studies, with the NTP study showing non
      linearity for all neoplasms. This may result from differences in the experimental
      protocols as well as divergence in the biological behavior of the different
      stocks of Sprague-Dawley rat strains used.

PMID- 16977595
TI  - Somatic microindels: analysis in mouse soma and comparison with the human
      germline.
AB  - Microindels, defined as mutations that result in a colocalized microinsertion and
      microdeletion with a net gain or loss of between 1 and 50 nucleotides, may be an
      important contributor to cancer. We report the first comprehensive analysis of
      somatic microindels. Our large database of mutations in the lacI transgene of Big
      Blue((R)) mice contains 0.5% microindels, 2.8% pure microinsertions, and 11.5%
      pure microdeletions. There appears to be no age, gender, or tissue-type
      specificity in the frequency of microindels. Of the independent somatic mutations
      that result in a net in-frame insertion or deletion, microindels are responsible
      for 13% of protein expansions and 6% of protein contractions. These in-frame
      microindels may play a crucial role in oncogenesis and evolution via "protein
      tinkering" (i.e., modest expansion or contraction of proteins). Four
      characteristics suggest that microindels are caused by unique mechanisms, not
      just simple combinations of the same mechanisms that cause pure microinsertions
      and pure microdeletions. First, microinsertions and microdeletions commonly occur
      at hotspots, but none of the 30 microindels are recurrent. Second, the sizes of
      the deletions and insertions in microindels are larger and more varied than in
      pure microdeletions and pure microinsertions. Third, microinsertions
      overwhelmingly repeat the adjacent base (97%) while the insertions in microindels
      do so only infrequently (17%). Fourth, analysis of the sequence contexts of
      microindels is consistent with unique mechanisms including recruitment of
      translesion DNA synthesis polymerases. The mouse somatic microindels have
      characteristics similar to those of human germline microindels, consistent with
      similar causative mechanisms in mouse and human, and in soma and germline.

PMID- 16977596
TI  - Mutations in the C7orf11 (TTDN1) gene in six nonphotosensitive
      trichothiodystrophy patients: no obvious genotype-phenotype relationships.
AB  - Trichothiodystrophy (TTD) is a rare autosomal recessive disorder whose defining
      feature is brittle hair. Associated clinical symptoms include physical and mental
      retardation of different severity, ichthyosis, premature aging, and, in half of
      the patients, photosensitivity. Recently, C7orf11 (TTDN1) was identified as the
      first disease gene for the nonphotosensitive form of TTD, being mutated in two
      unrelated cases and in an Amish kindred. We have evaluated the involvement of
      TTDN1 in 44 unrelated nonphotosensitive TTD cases of different geographic origin
      and with different disease severity. Mutations were found in six patients, five
      of whom are homozygous and one of whom is a compound heterozygote. All five
      identified mutations are deletions that have not been described before. Three are
      deletions of a few bases, resulting in frameshifts and premature termination
      codons. The other two include the whole TTDN1 gene, suggesting that TTDN1 is not
      essential for cell proliferation and viability. The severity of the clinical
      features does not correlate with the type of mutation, indicating that other
      factors besides TTDN1 mutations influence the severity of the disorder. Since
      only a small proportion of the analyzed cases were mutated in TTDN1, the
      nonphotosensitive form of TTD is genetically heterogeneous. Mutations in TTDN1 do
      not affect the response to ultraviolet (UV) light or the steady state level of
      the repair/transcription factor IIH (TFIIH), which is central to the onset of the
      photosensitive form of TTD.

PMID- 16977597
TI  - Asian American Network for Cancer Awareness, Research, and Training's legacy. The
      first 5 years.
AB  - The Asian American Network for Cancer Awareness, Research, and Training (AANCART)
      is the first special populations network for Asian Americans on a national basis
      and includes collaborating organizations from Boston, New York, Houston, Seattle,
      San Francisco, Los Angeles, Hawaii, and Sacramento (where it is headquartered at
      the University of California, Davis). NCI funding of AANCART in 2000 brought
      together investigators and leaders from 9 cities across 6 states to establish an
      infrastructure for addressing cancer awareness, research, and training. Since
      2000, AANCART has conducted needs assessments, held community awareness
      activities and trainings, trained trainees, sponsored National Asian American
      Cancer Control Academies, and produced presentations, publications, and grants.
      All specific aims have been attained, including the establishment of an
      infrastructure to promote Asian American cancer awareness, research, and training
      in 4 targeted regions; the establishment of partnerships to promote accrual to
      clinical trials, training, and pilot studies; and the formulation and successful
      implementation of grant-funded research to reduce the cancer burden among Asian
      Americans. AANCART's first 5 years have increased cancer awareness, trained
      special populations scientists, and advanced the field of Asian American cancer
      control research. Cancer 2006. (c) 2006 American Cancer Society.

PMID- 16977598
TI  - Enhancing cancer control programmatic and research opportunities for African
      Americans through technical assistance training.
AB  - African-Americans remain severely underrepresented in cancer control program
      delivery and research. Community-based organizational leaders and minority junior
      investigators have received little attention as representatives of target
      populations, or as agents to deliver and evaluate efforts to eliminate cancer
      health disparities. This paper describes activities of the National Black
      Leadership Initiative on Cancer II: Network Project, which has sought to address
      these issues. Community leaders and junior investigators received technical
      assistance (TA) and mentoring to develop applications for cancer education and
      community-based participatory research (CBPR) projects. TA was provided to 35
      community leaders and 32 junior investigators. Twenty-nine community leaders won
      funding through the Community Partners for Cancer Education Program. Three pilot
      research applications were funded. Technical assistance may improve minority
      recruitment/retention in CBPR cancer control research and enhance understanding
      and elimination of cancer health disparities among African-Americans. Cancer
      2006. (c) American Cancer Society.

PMID- 16977599
TI  - Building Native Hawaiian capacity in cancer research and programming. A legacy of
      'Imi Hale.
AB  - In 2000, cancer health indicators for Native Hawaiians were worse than those of
      other ethnic groups in Hawai'i, and Native Hawaiians were under-represented in
      research endeavors. To build capacity to reduce cancer health disparities, 'Imi
      Hale applied principles of community-based participatory research (CBPR) and
      empowerment theory. Strategies included: 1) engaging Native Hawaiians in defining
      cancer priorities; 2) developing culturally appropriate processes and products;
      3) supplementing primary and secondary cancer prevention activities; 4) offering
      skills training and technical assistance; and 5) providing an infrastructure to
      support culturally appropriate research. Between 2000 and 2005, 'Imi Hale
      involved more than 8000 Native Hawaiians in education, training, and primary and
      secondary prevention activities; developed 24 culturally tailored educational
      products (brochures, curricula, and self-help kits); secured $1.1 million in
      additional program and research funds; trained 98 indigenous researchers, 79 of
      whom worked on research projects; and engaged more than 3000 other Native
      Hawaiians as research participants and advisors. Evidence of empowerment was seen
      in increased individual competence, enhanced community capacity and
      participation, reduced barriers, and improved supports to address cancer in
      Hawaiian communities. Operationalizing CBPR and empowerment requires a commitment
      to involving as many people as possible, addressing community priorities,
      following cultural protocol, developing and transferring skills, and supporting
      an infrastructure to reduce barriers and build supports to sustain change. This
      approach is time consuming, but necessary for building competence and capacity,
      especially in indigenous and minority communities. Cancer 2006. (c) 2006 American
      Cancer Society.

PMID- 16977600
TI  - Creating alliances to improve cancer prevention and detection among urban
      medically underserved minority groups. The East Harlem Partnership for Cancer
      Awareness.
AB  - The East Harlem Partnership for Cancer Awareness (EHPCA) was formed in 1999 to
      reduce disparities in cancer screening and prevention among medically underserved
      minorities residing in a large urban community (East Harlem, New York City) by
      increasing awareness of cancer risk, prevention, and treatment, and promoting
      greater participation in breast, cervical, colorectal, and prostate cancer
      screening and early detection. The Partnership augments a 20-year collaboration
      between an academic medical center, a public hospital, and 2 community health
      centers. Needs assessments were conducted to inform program development. Cancer
      education, outreach, and screening programs were developed based on the PRECEED
      PROCEED model for health education and health promotion programming. Needs
      assessments revealed that although the majority of the population (86%) was
      insured and had a source of primary care, cancer screening guidelines for breast,
      cervical, prostate, and colorectal cancers were not being followed. Outreach
      strategies, targeted curricula, educational sessions, and screening programs have
      been developed and implemented to improve knowledge levels and increase screening
      participation. The EHPCA is a model of a successful partnership among the public
      and private sectors to reduce disparities in cancer screening and prevention in a
      diverse, medically underserved, urban minority community. Future efforts to
      reduce cancer screening disparities in this population will include patient
      navigation and improved access to standard-of-care screening such as colonoscopy.
      Cancer 2006. (c) 2006 American Cancer Society.

PMID- 16977601
TI  - Arkansas Special Populations Access Network perception versus reality--cancer
      screening in primary care clinics.
AB  - The origin of cancer health disparities and mortality in Arkansas is
      multifactorial. In response to a cooperative agreement with the National Cancer
      Institute's Center to Reduce Cancer Health Disparities, the Arkansas Special
      Populations Access Network (ASPAN) was developed to reduce these disparities.
      ASPAN's partnership with local primary care physicians of the Arkansas Medical,
      Dental, and Pharmaceutical Association through the Cancer Education Awareness
      Program is the focus of this article. A quasi-experimental intervention, the
      Community Cancer Education Awareness Program, was employed that included 1)
      physician education to increase awareness of risk factors and cancer screening;
      and 2) patient education to increase screening, and 3) patient-generated
      screening questionnaires to prompt discussion of cancer risk and screening
      recommendations between patients and physicians. Two urban and 2 rural clinics
      were targeted during a 12-month period with interval intervention assessments.
      Baseline review of records (n = 200) from patients >/=40 were utilized to assess
      the rate of breast, prostate, and colorectal screenings among clinics. For the
      patient education intervention, patients (n = 120) were interviewed via a 34-item
      assessment. Physician awareness of cancer risk factors and screening
      recommendations significantly increased. Statistically significant increases were
      seen for prostate (P = .028), breast (P = .036), and colorectal (P < .001) cancer
      screening across all 4 clinics. Patients' increased likelihood of cancer
      screenings was associated with knowledge about consumption of animal fat (P <
      .001), dietary fiber (P < .013), and mammograms (P < .001). Utilizing the
      physician as the central change agent, the ASPAN provider network successfully
      enhanced cancer screening awareness of minority physicians and their patients.
      Cancer 2006. (c) 2006 American Cancer Society.

PMID- 16977602
TI  - Challenge with innate and protein antigens induces CCR7 expression by microglia
      in vitro and in vivo.
AB  - Since activated microglia are able to phagocytose damaged cells and subsequently
      express major histocompatibility complex class II (MHC-II) and co-stimulatory
      proteins, they are considered to function as antigen presenting cells (APCs) in
      the central nervous system. The maturation and migratory potential of
      professional APCs is associated with the expression of chemokine receptor CCR7.
      We therefore investigated whether the immunological activation of microglia
      induces CCR7 expression. We here present that activation of cultured microglia by
      both the innate antigen lipopolysaccharide and protein antigen ovalbumin rapidly
      induces CCR7 expression, accompanied by increased MHC-II expression. Moreover, it
      is shown that CCR7 expression in IBA-1 positive cells is induced during the
      symptom onset and progression of experimental autoimmune encephalomyelitis, a
      rodent model for multiple sclerosis. These results suggest that microglia express
      CCR7 under specific inflammatory conditions, corroborating the idea that
      microglia develop into APCs with migratory potential toward lymphoid chemokines.

PMID- 16977603
TI  - Phenotypic and functional characteristics of mesenchymal stem cells
      differentiated along a Schwann cell lineage.
AB  - We have investigated the phenotypic and bioassay characteristics of bone marrow
      mesenchymal stromal cells (MSCs) differentiated along a Schwann cell lineage
      using glial growth factor. Expression of the Schwann cell markers S100, P75, and
      GFAP was determined by immunocytochemical staining and Western blotting. The
      levels of the stem cell markers Stro-1 and alkaline phosphatase and the neural
      progenitor marker nestin were also examined throughout the differentiation
      process. The phenotypic properties of cells differentiated at different passages
      were also compared. In addition to a phenotypic characterization, the functional
      ability of differentiated MSCs has been investigated employing a co-culture
      bioassay with dissociated primary sensory neurons. Following differentiation,
      MSCs underwent morphological changes similar to those of cultured Schwann cells
      and stained positively for all three Schwann cell markers. Quantitative Western
      blot analysis showed that the levels of S100 and P75 protein were significantly
      elevated upon differentiation. Differentiated MSCs were also found to enhance
      neurite outgrowth in co-culture with sensory neurons to a level equivalent or
      superior to that produced by Schwann cells. These findings support the assertion
      that MSCs can be differentiated into cells that are Schwann cell-like in terms of
      both phenotype and function.

PMID- 16977604
TI  - Hypoxia-induced astrocytic reaction and increased vascular permeability in the
      rat cerebellum.
AB  - Hypoxia is an important factor linked to induction of vascular leakage and
      formation of brain edema. In this connection, astrocytes associated closely with
      the blood vessels are deemed to be involved. This study investigated the response
      of astrocytes to hypoxia in the adult rat cerebellum, and along with this, the
      integrity of the blood-brain barrier (BBB) was assessed using fluorescent and
      electron dense tracers. In rats subjected to hypoxia, mRNA and protein expression
      of hypoxia inducible factor-1alpha (HIF-1alpha), vascular endothelial growth
      factor (VEGF), glial fibrillary acidic protein (GFAP), and aquaporin-4 (AQ4) was
      significantly increased. VEGF and AQ4 immunoreactive cells were identified as
      astrocytes by double immunofluorescence labeling. Increased VEGF tissue
      concentration and astrocytic swelling as observed in hypoxic rats were reduced
      after melatonin administration. Following intraperitoneal or intravenous
      injection of rhodamine isothiocyanate (RhIC) or horseradish peroxidase (HRP),
      leakage of both tracers was observed in hypoxic rats but not in the controls
      indicating that functional integrity of BBB is compromised in
      hypoxia/reoxygenation. Enhanced gene and protein expression of VEGF may
      contribute to increased permeability of blood vessels. AQ4, a water transporting
      protein, is upregulated in astrocytes in hypoxia suggesting the cells are
      involved in edema formation. To this end, melatonin may be beneficial in reducing
      edema as it reduced VEGF concentration and, hence, vascular permeability.

PMID- 16977605
TI  - Microglia instruct subventricular zone neurogenesis.
AB  - Microglia are increasingly implicated as a source of non-neural regulation of
      postnatal neurogenesis and neuronal development. To evaluate better the
      contributions of microglia to neural stem cells (NSCs) of the subventricular
      neuraxis, we employed an adherent culture system that models the continuing
      proliferation and differentiation of the dissociated neuropoietic subventricular
      tissues. In this model, neuropoietic cells retain the ability to self-renew and
      form multipotent neurospheres, but progressively lose the ability to generate
      committed neuroblasts with continued culture. Neurogenesis in highly expanded
      NSCs can be rescued by coculture with microglial cells or microglia-conditioned
      medium, indicating that microglia provide secreted factor(s) essential for
      neurogenesis, but not NSC maintenance, self-renewal, or propagation. Our findings
      suggest an instructive role for microglial cells in contributing to postnatal
      neurogenesis in the largest neurogenic niche of the mammalian brain.

PMID- 16977606
TI  - Mutations in the MYB intron I regulatory sequence increase transcription in colon
      cancers.
AB  - Although MYB overexpression in colorectal cancer (CRC) is known to be a
      prognostic indicator for poor survival, the basis for this overexpression is
      unclear. Among multiple levels of MYB regulation, the most dynamic is the control
      of transcriptional elongation by sequences within intron 1. The authors have
      proposed that this regulatory sequence is transcribed into an RNA stem-loop and
      19-residue polyuridine tract, and is subject to mutation in CRC. When this region
      was examined in colorectal and breast carcinoma cell lines and tissues, the
      authors found frequent mutations only in CRC. It was determined that these
      mutations allowed increased transcription compared with the wild type sequence.
      These data suggest that this MYB regulatory region within intron 1 is subject to
      mutations in CRC but not breast cancer, perhaps consistent with the mutagenic
      insult that occurs within the colon and not mammary tissue. In CRC, these
      mutations may contribute to MYB overexpression, highlighting the importance of
      noncoding sequences in the regulation of key cancer genes.

PMID- 16977607
TI  - High-grade mucoepidermoid carcinoma of the accessory parotid gland with distant
      metastases identified by 18F-FDG PET-CT.
AB  - We report a rare case of a metastatic mucoepidermoid carcinoma (MEC) arising from
      the accessory parotid gland in a 14-year-old male. In the pre-surgical
      assessment, the MR and CT showed no other abnormalities apart from the primary
      lesion. The lesion was excised and confirmed as a high-grade MEC. Four months
      later, he presented with a recurrence in his right temple. A (18)F-FDG PET-CT
      showed distal metastases in cervical nodes and lungs. In view of the findings and
      poor prognosis of the patient, surgical intervention and radiotherapy were not
      given and palliative measures offered. This case shows the potential of molecular
      imaging with (18)F-FDG PET-CT in these patients.

PMID- 16977608
TI  - Feasibility of ovarian tissue cryopreservation for prepubertal females with
      cancer.
AB  - BACKGROUND: Loss of fertility is one of the long-term adverse effects of high
      dose chemotherapy or total body irradiation for cancer, even in children. Ovarian
      tissue cryopreservation (OTC) may make it possible for survivors of childhood
      cancer to have children. We evaluated the feasibility of this technique for
      prepubertal girls. METHODS: Between September 2000 and February 2005, 49
      prepubertal girls were referred to the Reproductive Biology Unit for OTC before
      sterilizing treatment. RESULTS: One ovary each was collected from 47 patients, by
      laparoscopy in 24 patients and laporotomy in the others. In 16 cases, the ovary
      was harvested during laparotomy to resect a residual abdominal tumor. No
      complications occurred after operations. Ovarian tissue was frozen by a slow
      cooling protocol, using DMSO and sucrose as cryoprotectants. An mean of 17.6 +/-
      6.5 ovarian tissue fragments was cryopreserved per patient. Follicle
      concentration was evaluated histologically for 46 patients and a strong
      correlation was found between age and follicular density. None of the cases had
      visible ovarian tumor components. Ovarian cryopreservation was not carried out
      for two patients. CONCLUSION: The cryopreservation of ovarian tissue could be
      systematically offered even to prepubertal girls at risk of sterility due to
      gonadotoxic treatment.

PMID- 16977609
TI  - Emotion recognition patterns in patients with panic disorder.
AB  - Recognition of facially expressed emotions is essential in social interaction.
      For patients with social phobia, general anxiety disorders, and comorbid anxiety,
      deficits in their emotion recognition and specific biases have already been
      reported. This is the first study to investigate facial emotion recognition
      patterns in patients with panic disorder [PD]. We assumed a general performance
      deficit in patients with PD. Exploratory analyses should have revealed
      recognition patterns and specific types of errors. Additionally, we checked the
      influence of depression and anxiety symptoms, per se, on recognition. A carefully
      selected group of 37 patients with PD without agoraphobia [DSM-IV 300.01] and no
      psychiatric comorbidity was compared to 43 controls matched for age and sex. We
      assessed emotion recognition with the FEEL Test [Facially Expressed Emotion
      Labeling], using faces displaying fear, anger, sadness, happiness, disgust, and
      anger. Recognition of emotions in patients with PD was significantly worse than
      that of controls, specifically, sadness and anger. They also showed a tendency to
      interpret nonanger emotions as anger. Interestingly, in patients with PD,
      depressive symptoms were more strongly related to emotion recognition than were
      anxiety symptoms, and recognition differences between patients and controls
      disappeared when we controlled for depression. This effect is discussed in the
      context of previous studies reporting emotion recognition deficits of depressed
      patients.

PMID- 16977610
TI  - Nonlinear chiral interactions in resolutions with benzylamine derivatives.
AB  - N-formylphenylalanine was subjected to optical resolution using a chiral agent
      such as phenylethylamine enantiomer, (R)-phenylglycine methyl ester, (S)-N-benzyl
      2-aminobutanol, alone or in a mixture with each other or in a mixture with
      benzylamine.

PMID- 16977611
TI  - Performance of brush-type HPLC chiral stationary phases with tertiary amide in
      the connecting tether.
AB  - The replacement of the N-H hydrogen of the secondary amide-tethered Pirkle
      concept N-(3,5-dinitrobenzoyl)-L-leucine derived chiral stationary phase with
      various pi-basic or aliphatic groups improved the chiral discrimination ability
      of new chiral stationary phases, based on the leucine- or alanine-derived chiral
      selector, for the enantiomers of various racemic neutral analytes with amide
      functional groups. Retention times decreased while separation and resolution
      factors increased, thus proving the role of pi-donor aromatic unit as an electron
      rich shield in the front of a silica surface. In general, chiral stationary phase
      (CSP) 5 with the 3,5-dimethylphenyl unit showed best performance, while CSP 3,
      with phenyl unit, and CSP 7, with 1-naphthyl unit in the tertiary amide
      connecting tether, were less efficient.

PMID- 16977612
TI  - Optic nerve sheath fenestration with endoscopic accessory instruments versus the
      free electron laser (FEL).
AB  - BACKGROUND AND OBJECTIVE: The free electron laser (FEL) can efficiently produce
      an optic nerve sheath fenestration using an endoscopic approach. To develop a
      surgical protocol, this study compared effectiveness of available accessory
      endoscopic instruments to endoscopic FEL delivery effectiveness in producing
      optic nerve sheath fenestrations. STUDY DESIGN/MATERIALS AND METHODS: An
      endoscope was used to perform optic nerve sheath fenestrations on goat optic
      nerves. Accessory endoscopic instruments and glass-hollow waveguides (250 and 320
      microm in diameter) were inserted into the instrument channel for comparison. FEL
      energy (6.45 microm, 30 Hz) was delivered to the tissue through the waveguides
      and histological analysis was performed. RESULTS: The endoscopic instruments
      alone were unable to incise the optic nerve sheath. The FEL successfully incised
      the sheath and the biopsy forceps extricated the circular flap. CONCLUSIONS:
      Endoscopic optic nerve sheath fenestration using FEL energy followed by biopsy
      forceps for sheath extrication produced good results, thereby creating a feasible
      protocol for optic nerve sheath fenestration.

PMID- 16977613
TI  - Transdermal photodynamic therapy--a treatment option for rheumatic destruction of
      small joints?
AB  - BACKGROUND AND OBJECTIVE: Synovectomy of small joints is a therapeutic approach
      in patients suffering from rheumatoid arthritis (RA). We examined the feasibility
      of transdermal photodynamic therapy (tPDT) in a fibroblast-induced model of joint
      destruction using the novel photosensitizer (PS) tetrahydroporphyrin-tetratosylat
      that shows strong absorption at the near infra-red spectral region. MATERIALS AND
      METHODS: The functionality of the PDT system was assessed in vitro. Following
      arthritis induction and PS application, tPDT was applied in vivo. Therapy results
      were evaluated by measuring joint swelling, serum amyloid A (SAA) and
      histologically. RESULTS: We were able to present a fully functional PDT in vitro.
      The in vivo therapy modalities were well tolerated by mice. We could demonstrate
      photodynamic ablation of subcutaneously located tissue (skeletal muscle) without
      skin damage. CONCLUSION: This study provides the basis for transdermal
      accessibility of tissue through a photodynamic process which may serve as a
      minimally invasive synovectomy strategy.

PMID- 16977616
TI  - Ultrastructure of synaptic input to medial olivocochlear neurons.
AB  - Medial olivocochlear (MOC) neurons project from the brain to the cochlea to form
      the efferent limb of the MOC reflex. To study synaptic inputs to MOC neurons, we
      retrogradely labeled these neurons using horseradish peroxidase injections into
      the cochlea. Labeled neurons were identified in the ventral nucleus of the
      trapezoid body and documented with the light microscope before being studied with
      serial-section electron microscopy. MOC somata and dendrites were innervated by
      three different types of synapses, distinguished as either having: 1) large,
      round synaptic vesicles and forming asymmetric contacts; 2) small, round vesicles
      plus a few dense core vesicles and forming asymmetric contacts; or 3) pleomorphic
      vesicles and forming symmetric contacts. The first two types were the most
      frequent on somata. Acetylcholinesterase-stained material confirmed that the type
      containing large, round vesicles is most common on dendrites. We kept track of
      the synaptic terminals in serial sections and compiled them into three
      dimensional swellings. Swellings with large, round vesicles formed up to seven
      synapses per swelling, were largest in size, and sometimes formed complex
      arrangements engulfing spines of MOC neurons. Swellings with small, round
      vesicles formed up to four synapses per swelling. The morphology of this type of
      synapse, and the moderate sizes of the swellings forming it, suggests that it
      originates from posteroventral cochlear nucleus stellate/multipolar neurons. This
      input may thus provide the sound-evoked input to MOC neurons that causes their
      reflexive response to sound.

PMID- 16977615
TI  - Differential synaptology of vGluT2-containing thalamostriatal afferents between
      the patch and matrix compartments in rats.
AB  - The striatum is divided into two compartments named the patch (or striosome) and
      the matrix. Although these two compartments can be differentiated by their
      neurochemical content or afferent and efferent projections, the synaptology of
      inputs to these striatal regions remains poorly characterized. By using the
      vesicular glutamate transporters vGluT1 and vGluT2, as markers of corticostriatal
      and thalamostriatal projections, respectively, we demonstrate a differential
      pattern of synaptic connections of these two pathways between the patch and the
      matrix compartments. We also demonstrate that the majority of vGluT2
      immunolabeled axon terminals form axospinous synapses, suggesting that thalamic
      afferents, like corticostriatal inputs, terminate preferentially onto spines in
      the striatum. Within both compartments, more than 90% of vGluT1-containing
      terminals formed axospinous synapses, whereas 87% of vGluT2-positive terminals
      within the patch innervated dendritic spines, but only 55% did so in the matrix.
      To characterize further the source of thalamic inputs that could account for the
      increase in axodendritic synapses in the matrix, we undertook an electron
      microscopic analysis of the synaptology of thalamostriatal afferents to the
      matrix compartments from specific intralaminar, midline, relay, and associative
      thalamic nuclei in rats. Approximately 95% of PHA-L-labeled terminals from the
      central lateral, midline, mediodorsal, lateral dorsal, anteroventral, and ventral
      anterior/ventral lateral nuclei formed axospinous synapses, a pattern reminiscent
      of corticostriatal afferents but strikingly different from thalamostriatal
      projections arising from the parafascicular nucleus (PF), which terminated onto
      dendritic shafts. These findings provide the first evidence for a differential
      pattern of synaptic organization of thalamostriatal glutamatergic inputs to the
      patch and matrix compartments. Furthermore, they demonstrate that the PF is the
      sole source of significant axodendritic thalamic inputs to striatal projection
      neurons. These observations pave the way for understanding differential
      regulatory mechanisms of striatal outflow from the patch and matrix compartments
      by thalamostriatal afferents.

PMID- 16977617
TI  - Binding and complementary expression patterns of semaphorin 3E and plexin D1 in
      the mature neocortices of mice and monkeys.
AB  - Although axon guidance molecules play critical roles in neural circuit formation
      during development, their roles in the adult circuit are not well understood. In
      this study we examined the expression patterns of Semaphorin 3E (Sema3E), a
      member of the semaphorin family, in the mature neocortices of monkeys and mice by
      in situ hybridization (ISH). We found that Sema3E mRNA is highly specific to
      layer VI throughout the macaque monkey neocortex. We further examined the ratio
      of Sema3E+ cells among the layer VI excitatory neurons in areas M1, S1, TE, and
      V1 by fluorescence double ISH, using the vesicular glutamate transporter 1
      (VGluT1) gene as a specific marker for excitatory neurons. Among these areas, 34
      63% of the VGluT1+ neurons expressed Sema3E mRNA. In the mouse cortex, two
      significant differences were observed in the pattern of Sema3E mRNA distribution.
      1) Sema3E mRNA was expressed in layer Vb, in addition to layer VI in mice. 2) A
      subset of GABAergic interneurons expressed Sema3E mRNA in mice. By an in vitro
      binding experiment, we provide evidence that Plexin D1 is the specific receptor
      for Sema3E. Plexin D1 mRNA was preferentially expressed in layers II-V in both
      monkey and mouse cortices. The detailed lamina analysis by double ISH, however,
      revealed that Plexin D1 mRNA is expressed in layers II-Va, but not in layer Vb in
      the mouse cortex. Thus, the Plexin D1 and Sema3E mRNAs exhibit conserved
      complementary lamina patterns in mice and monkeys, despite the species
      differences in the pattern of each gene.

PMID- 16977618
TI  - Aligned neurite bundles of granule cells regulate orientation of Purkinje cell
      dendrites by perpendicular contact guidance in two-dimensional and three
      dimensional mouse cerebellar cultures.
AB  - To identify structures that determine the 90 degree orientation of thin espalier
      dendritic trees of Purkinje cells with respect to parallel fibers (axonal neurite
      bundles of granule cells) in the cerebellar cortex, we designed five types of two
      dimensional and three-dimensional cell and tissue cultures of cerebella from
      postnatal mice and analyzed the orientation of Purkinje cell dendrites with
      respect to neurite bundles and astrocyte fibers by immunofluorescence double or
      triple staining. We cultured dissociated cerebellar cells on micropatterned
      substrates and preformed neurite bundles of a microexplant culture two
      dimensionally and in matrix gels three-dimensionally. Dendrites, but not axons,
      of Purkinje cells extended toward the neurites of granule cells and oriented at
      right angles two-dimensionally to aligned neurite bundles in the three cultures.
      In a more organized explant proper of the microexplant culture, Purkinje cell
      dendrites extended toward thin aligned neurite bundles not only consistently at
      right angles but also two-dimensionally. However, in the "organotypic
      microexplant culture," in which three-dimensionally aligned thick neurite bundles
      mimicking parallel fibers were produced, Purkinje cell dendrites often oriented
      perpendicular to the thick bundles three-dimensionally. Astrocytes were abundant
      in all cultures, and there was no definite correlation between the presence of
      and orientation to Purkinje cell dendrites, although their fibers were frequently
      associated in parallel with dendrites in the organotypic microexplant culture.
      Therefore, Purkinje cells may grow their dendrites to the newly produced neurite
      bundles of parallel fibers in the cerebellar cortex and be oriented at right
      angles three-dimensionally mainly via "perpendicular contact guidance."

PMID- 16977619
TI  - Severe alcohol-induced neuronal deficits in the hippocampus and neocortex of
      neonatal mice genetically deficient for neuronal nitric oxide synthase (nNOS).
AB  - Alcohol can severely damage the developing brain, and neuronal loss is a critical
      component of this injury. Thus, identification of molecular factors that
      ameliorate alcohol-induced neuronal loss is of great importance. Previous in
      vitro work has demonstrated that nitric oxide (NO) protects neurons against
      alcohol toxicity. We tested the hypothesis that neonatal mice carrying a null
      mutation for neuronal nitric oxide synthase (nNOS), the enzyme that synthesizes
      NO in neurons, have an increased vulnerability to alcohol-induced neuronal loss
      in the neocortex and hippocampus. Wildtype mice and nNOS-/- mice received ethanol
      (0.0, 2.2, 3.3, or 4.4 g/kg) daily over postnatal days (P) 4-9 and were
      sacrificed on P10. The number of hippocampal CA1 and CA3 pyramidal cells, dentate
      gyrus granule cells, and neocortical neurons were determined using stereological
      methods. Alcohol pharmacokinetics did not differ between wildtype and nNOS-/-
      strains. Alcohol induced dose-dependent reductions in all four neuronal
      populations, and the losses were substantially more severe in the nNOS-/- mice
      than in wildtype. Furthermore, the threshold dose of alcohol to induce cell death
      was lower in the nNOS-/- mice than in the wildtype mice for all neuronal
      populations. While nNOS deficiency worsened alcohol-induced neuronal losses, the
      magnitude of this exacerbation varied among brain regions and depended on alcohol
      dose. These results demonstrate that nNOS deficiency decreases the ability of
      developing neurons in vivo to survive the toxic effects of alcohol and strengthen
      the hypothesis that NO exerts a neuroprotective effect against alcohol toxicity
      in the developing brain.

PMID- 16977620
TI  - Effect of heat-shock proteins for relieving physiological stress and enhancing
      the production of penicillin acylase in Escherichia coli.
AB  - High-level expression of recombinant penicillin acylase (PAC) using the strong
      trc promoter system in Escherichia coli is frequently limited by the processing
      and folding of PAC precursors (proPAC) in the periplasm, resulting in
      physiological stress and inclusion body formation in this compartment.
      Periplasmic heat-shock proteins with protease or chaperone activity potentially
      offer a promise for overcoming this technical hurdle. In this study, the effect
      of the two genes encoding periplasmic heat-shock proteins, that is degP and fkpA,
      on pac overexpression was investigated and manipulation of the two genes to
      enhance the production of recombinant PAC was demonstrated. Both DeltadegP and
      DeltafkpA mutants showed defective culture performance primarily due to growth
      arrest. However, pac expression level was not seriously affected by the
      mutations, indicating that the two proteins were not directly involved in the
      pathway for periplasmic processing of proPAC. The growth defect caused by the two
      mutations (i.e., DeltadegP and DeltafkpA) was complemented by either one of the
      wild-type proteins, implying that the function of the two proteins could
      partially overlap in cells overexpressing pac. The possible role that the two
      heat-shock proteins played for suppression of physiological stress caused by pac
      overexpression is discussed.

PMID- 16977621
TI  - Characterization of an experimental miniature bioreactor for cellular
      perturbation studies.
AB  - A mini bioreactor (3.0 mL volume) has been developed and shown to be a versatile
      tool for rapidly screening and quantifying the response of organisms on
      environmental perturbations. The mini bioreactor is essentially a plug flow
      device transformed into a well-mixed reactor by a recycle flow of the broth. The
      gas and liquid phases are separated by a silicone membrane. Dynamic mass transfer
      experiments were performed to determine the mass transfer capacities for oxygen
      and carbon dioxide. The mass transfer coefficients for oxygen and carbon dioxide
      were found to be 1.55 +/- 0.17 x 10(-5) m/s and 4.52 +/- 0.60 x 10(-6) m/s,
      respectively. Cultivation experiments with the 3.0 mL bioreactor show that (i) it
      can maintain biomass in the same physiological state as the 4.0 L lab scale
      bioreactor, (ii) reproducible perturbation experiments such as changing substrate
      uptake rate can be readily performed and the physiological response monitored
      quantitatively in terms of the O2 and CO2 uptake and production rates.

PMID- 16977622
TI  - Ultrastructural synaptic features differ between alpha- and gamma-motoneurons
      innervating the tibialis anterior muscle in the rat.
AB  - We investigated the synaptology of retrogradely labeled spinal motoneurons after
      injection of horseradish peroxidase into the tibialis anterior (TA) muscle of
      adult rat. In total, 32 TA motoneurons were investigated in the electron
      microscope and demonstrated a bimodal size distribution with cell diameter peaks
      at 40 microm and 20 microm, likely representing alpha- and gamma-motoneurons,
      respectively. Both alpha- and gamma-motoneurons were apposed by S- and F-type
      synaptic boutons, whereas only alpha-motoneurons demonstrated inputs by the large
      M- and C-type boutons. The proportion of cell body membrane covered by synaptic
      inputs was surprisingly indistinguishable between alpha-motoneurons (72.2%) and
      gamma-motoneurons (63.5%). The ratio between the number of F- and S-type boutons
      in apposition with the motoneuron cell body (F/S ratio) and the ratio between the
      soma membrane coverage provided by F- and S-type boutons were both significantly
      higher in alpha- than in gamma-motoneurons. When comparing our data with previous
      findings in other species, we conclude that rat TA alpha-motoneurons are similar
      to cat and primate alpha-motoneurons with regard to synaptic terminal morphology,
      frequency, and distribution. However, rat gamma-motoneurons show a markedly
      higher total synaptic coverage and frequency than cat gamma-motoneurons, although
      both species exhibit appositions made by the same synaptic types and similar
      ratios between inhibitory and excitatory inputs.

PMID- 16977623
TI  - Fiber connections of the compact division of the posterior pallial amygdala and
      lateral part of the bed nucleus of the stria terminalis in the pigeon (Columba
      livia).
AB  - The compact division of the posterior pallial amygdala (PoAc) and lateral part of
      the bed nucleus of the stria terminalis (BSTL) are components of the limbic
      system in the pigeon brain. In this study, we examined the position and fiber
      connections of these two nuclei by using Nissl staining and tract-tracing
      methods. PoAc occupies a central division in the posterior pallial amygdala. BSTL
      faces the ventral horn of the lateral ventricle and extends between A 7.25 and A
      10.50. PoAc and BSTL connect bidirectionally by the stria terminalis. PoAc
      connects reciprocally with two nuclear groups in the cerebrum: 1) a continuum
      consisting of the caudoventral nidopallium, lateral part of the caudoventral
      nidopallium (NCVl), subnidopallium beneath NCVl, and piriform cortex and 2)
      rostral areas of the hemisphere, including the frontolateral and frontomedial
      nidopallium and the densocellular part of the hyperpallium. Extratelencephalic
      projections of PoAc terminate in the dorsomedial thalamic nuclei and reach the
      lateral hypothalamic area via the hypothalamic part of the occipito-mesencephalic
      tract. BSTL also connects reciprocally with two main regions: 1) the same
      continuum as for PoAc projections, except the piriform cortex and 2) rostral
      areas of the hemisphere, including the olfactory tubercle and nucleus accumbens.
      Extratelencephalic reciprocal connections are with the substantia nigra, nucleus
      subceruleus dorsalis, parabrachial nucleus, locus coeruleus, and nucleus of the
      solitary tract. The dorsomedial subdivision of the hippocampal formation projects
      massively to PoAc and BSTL. These findings indicate that PoAc and BSTL are
      important components of an interconnected neural circuit involving widespread
      regions of the neuraxis and mediating limbic-visceral functions.

PMID- 16977624
TI  - Neural correlates of semantic and morphological processing of Hebrew nouns and
      verbs.
AB  - Neuropsychological evidence regarding grammatical category suggests that deficits
      affecting verbs tend to localize differently from those affecting nouns, but
      previous functional imaging studies on healthy subjects fail to show consistent
      results that correspond to the clinical dissociation. In the current imaging
      study, we addressed this issue by manipulating not only the grammatical category
      but also the processing mode, using auditory presentation of Hebrew words.
      Subjects were presented with verbs and nouns and were instructed to make either a
      semantic decision ("Does the word belong to a given semantic category?") or a
      morphological decision ("Is the word inflected in plural?"). The results showed
      different patterns of activation across distinct regions of interest. With
      respect to grammatical category effects, we found increased activation for verbs
      in the posterior portion of the left superior temporal sulcus, left dorsal
      premotor area, and posterior inferior frontal gyrus. In each of these regions,
      the effect was sensitive to task. None of the ROIs showed noun advantage. With
      respect to task effects, we found a semantic advantage in left anterior inferior
      frontal gyrus, as well as in left posterior middle temporal gyrus. The results
      suggest that cerebral verb-noun dissociation is a result of localized and subtle
      processes that take place in a set of left frontal and temporal regions, and that
      the cognitive and neural processes involved in analyzing grammatical category
      depend on the lexical characteristics of the stimuli, as well as on task
      requirements. The discrepancy between functional imaging and patient data is also
      discussed.

PMID- 16977625
TI  - Alzheimer's disease presenting as corticobasal syndrome.
AB  - A 60-year-old man presented with slowly progressive left hemi-Parkinsonism, left
      hand apraxia, myoclonus, dystonia, visuospatial disturbances, and alien limb
      phenomenon, resembling corticobasal syndrome. Eight years later, neuropathology
      revealed features of Alzheimer's disease, with asymmetrical (right more than
      left) cortical tau burden with image analysis. The videotaped clinical features,
      neuropsychological aspects, and neuropathological correlates are presented and
      discussed.

PMID- 16977626
TI  - Organization of primary afferent projections to the gracile nucleus of the dorsal
      column system of primates.
AB  - In order to reveal the somatotopic organization of the gracile nucleus of the
      dorsal column-trigeminal complex, neuroanatomical tracers were injected
      subcutaneously into various parts of the hindlimb and tail of prosimian galagos,
      New World monkeys, and Old World monkeys. In most cases, tracers were injected
      bilaterally, and into more than one body part. In six cases, two different,
      distinguishable tracers were injected into the same hindlimb. Brainstem and
      spinal cord sections were processed for tracers transported by cutaneous
      afferents to terminations in the gracile nuclei. Foci of terminations were
      related to the cell-cluster architecture of the gracile nuclei in sections
      processed for cytochrome oxidase or stained for cell bodies (Nissl stain). In all
      taxa, terminations labeled by the injections were distributed in a patchy fashion
      along the rostrocaudal length of the ipsilateral gracile nucleus. Terminations
      were largely but not completely focused within the cytochrome oxidase dense cell
      clusters. Across taxa, afferents from the tail, foot, lower leg, and upper leg
      terminated in a mediolateral sequence within the gracile nucleus. Afferents from
      the glabrous skin of toes 1-5 terminated in a ventromedial to dorsolateral
      sequence in owl, squirrel, and macaque monkeys, but an altered arrangement was
      seen in the galagos, with a ventrolateral location for toe 1. The use of two
      tracers in squirrel monkeys indicated that terminations from adjacent toes formed
      adjacent and largely segregated patches. Terminations of afferents from the
      plantar pad (sole) of the foot tended to surround those from the glabrous toes.

PMID- 16977627
TI  - Condensation of nonstochiometric DNA/polycation complexes by divalent cations.
AB  - This study found that divalent cations induced the further condensation of
      partially condensed DNA within nonstochiometric polycation complexes. The
      addition of a few mmol of a divalent cation such as calcium reduced by half the
      inflection point at which DNA became fully condensed by poly-L-lysine (PLL) and a
      variety of other polycations. The effect on DNA condensation was initially
      observed using a new method, which is based on the concentration-dependent self
      quenching of fluorescent moieties (e.g., rhodamine) covalently linked to the DNA
      backbone at relatively high densities. Additional analyses, which employed
      ultracentrifugation, dynamic light scattering, agarose gel electrophoresis, and
      atomic force microscopy, confirmed the effect of divalent cations. These results
      provide an additional accounting of the process by which divalent cations induce
      greater chromatin compaction that is based on the representation of chromatin
      fibers as a nonstoichiometric polyelectrolyte complex. They also offer a new
      approach to assemble nonviral vectors for gene therapy.

PMID- 16977628
TI  - NR4A2 genetic variation in sporadic Parkinson's disease: a genewide approach.
AB  - The NR4A2 gene, which may cause autosomal dominant Parkinson's disease (PD), has
      also been reported to be a susceptibility factor for sporadic PD. Here, we use a
      haplotype-tagging approach in 802 PD patients and 784 controls and demonstrate
      that common genetic variation, including NR4A2 haplotypes, does not influence the
      risk of PD in the Caucasian population.

PMID- 16977629
TI  - Mitral cells in the olfactory bulb of adult zebrafish (Danio rerio): morphology
      and distribution.
AB  - The mitral cell is the primary output neuron and central relay in the olfactory
      bulb of vertebrates. The morphology of these cells has been studied extensively
      in mammalian systems and to a lesser degree in teleosts. This study uses
      retrograde tract tracing and other techniques to characterize the morphology and
      distribution of mitral cells in the olfactory bulb of adult zebrafish, Danio
      rerio. These output neurons, located primarily in the glomerular layer and
      superficial internal cell layer, had variable-shaped somata that ranged in size
      from 4-18 microm in diameter and 31-96 microm2 in cross-sectional area. The
      mitral cells exhibited two main types of morphologies with regard to their
      dendrites: the unidendritic morphology was a single primary dendrite with one or
      more tufts, but multidendritic cells with several dendritic projections also were
      seen. The axons of these cells projected to either the medial or the lateral
      olfactory tract and, in general, the location of the cell on the medial or
      lateral side of the bulb was indicative of the tract to which it would project.
      Further, this study shows that the majority of zebrafish mitral cells likely
      innervate a single glomerulus rather than multiple glomeruli. This information is
      contrary to the multiple innervation pattern suggested for all teleost mitral
      cells. Our findings suggest that mitral cells in zebrafish may be more similar to
      mammalian mitral cells than previously believed, despite variation in size and
      structure. This information provides a revised anatomical framework for olfactory
      processing studies in this key model system.

PMID- 16977630
TI  - Vaccination of advanced prostate cancer patients with PSCA and PSA peptide-loaded
      dendritic cells induces DTH responses that correlate with superior overall
      survival.
AB  - Prostate stem cell antigen (PSCA) and prostate-specific antigen (PSA) are
      overexpressed in most prostate cancers. PSCA- and PSA-derived, HLA-A2 binding
      peptides are specific targets for T-cell responses in vitro. A phase I/II trial
      was performed to demonstrate feasibility, safety and induction of antigen
      specific immunity by vaccination with dendritic cells (DC) presenting PSCA and
      PSA peptides in patients with hormone- and chemotherapy-refractory prostate
      cancer. Patients received 4 vaccinations with a median of 2.7 x 10(7) peptide
      loaded mature DC s.c. in biweekly intervals. Clinical responses were assessed 2
      weeks after the 4th vaccination. Immune monitoring was performed by DTH and HLA
      multimer analysis. Twelve patients completed vaccination without relevant
      toxicities. Six patients had stable disease after 4 vaccinations. One patient had
      a complete disappearance of lymphadenopathy despite rising PSA. Four patients
      with SD and 1 progressor developed a positive DTH after the 4th vaccination. With
      a median survival of all patients of 13.4 months, DTH-positivity was associated
      with significantly superior survival (p = 0.003). HLA tetramer analysis detected
      high frequencies of peptide-specific T cells after 2 vaccinations in 1 patient
      who was also the sole responder to concomitant hepatitis B vaccination as an
      indicator of immune competence and survived 27 months after start of vaccination.
      Vaccination with PSA/PSCA peptide-loaded, autologous DCs may induce cellular
      responses primarily in immunocompetent patients, which appear to be associated
      with clinical benefit. Testing of DC-based vaccination is warranted for patients
      at earlier stages of prostate cancer.

PMID- 16977631
TI  - Nanomechanical force measurements of gliadin protein interactions.
AB  - The strength and nature of interactions between monomeric gliadin proteins
      involving alpha-alpha, omega-omega, and alpha-omega interactions in 0.01M acetic
      acid, and the effect of urea has been investigated. It was shown by means of
      nanomechanical force measurements that the stretching events in the separation
      curve after adhesive phenomena originated from proteins. These stretching events
      displayed different responses of the alpha- and omega-gliadins to urea. While 2M
      urea caused the more globular alpha-gliadins to unfold, the beta-turn-rich omega
      gliadins remained fairly stable even in 8M urea. This suggests different roles
      for gliadins in the formation of dough; while the omega-gliadins are still in a
      compact structure being responsible for the viscous flow, the alpha-gliadins have
      already started to participate in forming the network in dough.

PMID- 16977632
TI  - Direct medical costs associated with Parkinson's disease: a population-based
      study.
AB  - The objective was to provide population-based estimates of incremental medical
      costs associated with Parkinson's disease (PD) from onset forward. All Olmsted
      County, Minnesota, residents with confirmed PD onset from 1987 through 1995 (n =
      92) and one age- and sex-matched non-PD referent subject per case were identified
      with retrospective record review and followed in provider-linked billing data for
      direct medical costs (excluding outpatient pharmaceutical costs) from 1 year
      before index (i.e., year of symptom onset) through 10 years after index. Costs
      for each referent subject were subtracted from those for his/her matched case.
      Tests for statistical significance used Wilcoxon signed ranks. Preindex costs
      were similar [median difference in annual costs (MD) = -3 dollars; P = 0.59]. One
      year post index, PD subjects exhibited borderline significantly higher costs
      compared to referent subjects (MD = 581 dollars; P = 0.052); the difference
      diminished over 5 years (MD = 118 dollars; P = 0.82). By 5 to 10 years, however,
      PD subjects exhibited significantly higher costs (MD = 1,146 dollars; P = 0.01).
      Over the full 10 years, excess costs were concentrated among PD subjects without
      rest tremor (MD = 2,261 dollars, P < 0.01, for those without tremor and -229
      dollars, P = 0.99, for those with tremor). These population-based estimates of PD
      associated direct medical costs from onset forward can uniquely inform policy
      decisions and cost-effectiveness research.

PMID- 16977633
TI  - Prognostic value of neutrophils and NK cells in bronchoalveolar lavage of
      sarcoidosis.
AB  - BACKGROUND: Not all the patients with sarcoidosis need pharmacological therapy,
      and the decision to start therapy is based mainly on clinical conditions. The aim
      of this study was to evaluate the prognostic value of the leukocyte and
      lymphocyte subpopulations in the bronchoalveolar lavage fluid from these
      patients. METHODS: Thirty-three nonsmoking patients with sarcoidosis were
      included and classified based on the presence of Lofgren's syndrome (n = 11), the
      radiological stage (12 at Stage I, 17 at Stage II, and 4 at Stage III), and their
      follow-up. Differential leukocyte subsets and the lymphocyte subpopulations were
      determined by flow cytometry. RESULTS: The percentage of neutrophils was lower in
      patients with Lofgren's syndrome (P = 0.038) and in patients at Stage I (P =
      0.002). Patients with a poor outcome had a higher percentage of neutrophils (P =
      0.004) and NK cells (P = 0.023) than those with a stable disease. Finally, a
      higher percentage of NK cells was found in those patients who needed a steroid
      treatment (P = 0.012). CONCLUSIONS: Increased percentages of neutrophils and NK
      cells in the bronchoalveolar lavage fluid from patients with sarcoidosis are
      associated with a poor outcome and a higher probability to need steroids
      treatment. The percentage of neutrophils was also lower in patients with
      Lofgren's syndrome.

PMID- 16977634
TI  - Automated virtual microscopy of gastric biopsies.
AB  - BACKGROUND: Automated virtual microscopy of specimens from gastrointestinal
      biopsies is based on cytometric parameters of digitized histological sections. To
      our knowledge, cytometric parameters of gastritis and of adenocarcinoma have yet
      to be fully characterized. Our objective was to classify gastritis and
      adenocarcinoma based on cytometric parameters. We hypothesized that automated
      virtual microscopy using this novel classification can reliably diagnose
      gastritis and adenocarcinoma. METHODS: Routinely processed hematoxylin-and-eosin
      stained histological sections from specimens that showed normal mucosa (14
      cases), gastritis (35 cases), and adenocarcinoma (30 cases) diagnosed by
      conventional optical microscopy were scanned and digitized at high resolution.
      Thirty-eight cytometric parameters based on density and morphometry were applied
      to glands and superficial epithelium. Twelve cytometric parameters based on
      cytologic detail were applied to individual cells. RESULTS: Statistically
      significant differences in cytometric parameters for normal mucosa, gastritis,
      and adenocarcinoma were found. The most discriminatory parameter was the ratio of
      the total number of cells to the number of interstitial cells. These differences
      correctly classified adenocarcinoma at 100% accuracy and overall correctness was
      86%. CONCLUSIONS: We describe a novel method of analyzing gastric mucosal
      histology based on cytometric parameters. Automated virtual microscopy can be
      used to classify gastric mucosa as normal, gastritis, or adenocarcinoma with
      reasonable accuracy. Further research is necessary to determine whether automated
      virtual microscopy can subclassify gastric mucosal histology in greater detail.

PMID- 16977635
TI  - Flow cytometric assessment of autologous gammadelta T cells in patients with
      acute myeloid leukemia: potential effector cells for immunotherapy?
AB  - BACKGROUND: Gammadelta T cells are a rare component of the circulating innate
      immune system capable of exerting anti-neoplastic activity. This population may
      be suitable for the adoptive immunotherapy of acute myeloid leukemia (AML).
      Little is known however, about the frequency and function of circulating
      gammadelta T cells in AML. The aim of the study was to enumerate peripheral blood
      gammadelta T cells in patients with AML and explore the feasibility of their use
      clinically. METHODS: We compared the absolute circulating gammadelta T cell
      levels in 33 AML patients before and after treatment versus 20 healthy volunteers
      using flow cytometry. The function of gammadelta T cells was assessed by
      detection of intracelluar interferon-gamma (IFN-gamma) and cytotoxicity against
      leukemic blasts. RESULTS: AML patients with high blast counts prior to induction
      chemotherapy had marginally decreased gammadelta T cell levels compared with
      healthy controls: median 38/microL versus 83/microL; P = 0.051. Sequential
      gammadelta T cell enumeration after induction showed significantly decreased
      counts in patients with a persistently high blast burden compared to patients
      with reduced but detectable residual disease (molecular maker or borderline bone
      marrow infiltration): median 7/microL versus 105/microL; P = 0.008. Patients with
      residual disease had significantly higher gammadelta T cell counts compared to
      those retested after they had achieved complete remission (CR); P = 0.0025. In
      CR, gammadelta T cell counts remained lower than those of healthy individuals:
      median 33/microL versus 83/microL, P = 0.030. We detected a sharp increase (on
      average, four-fold higher than values in CR) of gammadelta T cells in patients in
      very early morphologic or molecular relapse. We also tested the functional
      properties of gammadelta T cells from patients with AML in CR. Flow cytometric
      assessment of IFN-gamma revealed similar numbers of gammadelta T cells expressing
      the T1 cytokine compared with healthy controls. We also showed that gammadelta T
      cells were able to kill leukemic target cells in vitro. CONCLUSION: Flow
      cytometric assessment of gammadelta T cells in patients with AML revealed
      quantitative shifts with respect to disease status. Our data suggest that
      gammadelta T cells warrant further investigation as potential therapeutic agents.

PMID- 16977636
TI  - Cytoadherence between endothelial cells and P. falciparum infected and
      noninfected normal and thalassemic red blood cells.
AB  - BACKGROUND: Cytoadhesion of P. falciparum infected red blood cells (RBCs) to
      endothelial cells (ECs) is an important phenomenon that causes cerebral malaria
      in man. Reduced adhesion especially in thalassemia and hemoglobinopathies may be
      related to a protective mechanism against malaria in such people. METHODS: The
      cytoadherence assay was performed using both conventional and floating conditions
      between ECs (ECV 304) and P. falciparum infected and noninfected RBCs from both
      normal and thalassemia subjects. In floating condition, RBC was fluorescently
      labeled with anti-glycophorin A antibody, whereas EC was identified by surface
      expression of PECAM-1, CD-36, ICAM-1, and E-selectin. The condition of floating
      EC was similar to the condition for subcultivation as they can adhere or bind to
      any surface. The phosphatidylserine (PS) exposure was also determined by using
      flow cytometer. RESULTS: The adhesion of noninfected heterozygous thalassemic
      RBCs (all genotypes) to ECs was significantly increased as compared with normal
      RBCs (P < 0.02). Interestingly, after P. falciparum infection, the number of
      normal RBCs bound to ECs was significantly increased as compared with noninfected
      RBCs (P < 0.01), whereas heterozygous thalassemic RBCs infected by P. falciparum
      showed no significant difference compared with noninfected RBCs. In addition, we
      found a similar level of PS exposure in normal and thalassemic infected RBCs,
      which was related to the cytoadherence phenomenon. CONCLUSION: The reduced
      adhesion between heterozygous thalassemic RBCs infected by P. falciparum to ECs
      provides an explanation for their protective mechanism against malaria, as
      increased adhesion is a high risk for cerebral malaria and nonbinding infected
      RBCs can be removed by the reticuloendothelial system and other mechanism(s) in
      vivo.

PMID- 16977637
TI  - Optimization of a flow cytometry-based protocol for detection and phenotypic
      characterization of multipotent mesenchymal stromal cells from human bone marrow.
AB  - BACKGROUND: To study the biology of rare bone marrow (BM) multipotent mesenchymal
      stromal cells (MSCs), recognized protocols are needed. Colony-forming unit
      fibroblast (CFU-F) assays have historically been used for the enumeration of
      MSCs. However, the need to isolate and further analyze MSCs requires new
      strategies based on cell surface markers. The purpose of this work was to verify
      the phenotype of BM MSCs in vivo and to develop flow cytometry-based methods for
      their evaluation. METHODS: Pre-enrichment with D7-FIB-conjugated microbeads, cell
      sorting for CD45low D7-FIB+ LNGFR+ cells, and CFU-F assay were used to confirm
      the phenotype of BM MSCs in vivo. Further phenotypic characterization of MSCs was
      performed using three-color flow cytometry following pre-enrichment or by direct
      four-color flow cytometry. The sensitivity of direct flow cytometry/rare event
      analysis for the accurate enumeration of MSCs was validated using 85 samples from
      patients with neoplastic BM diseases. RESULTS: In normal BM, a significant
      correlation was found between the frequencies of CFU-Fs and CD45low D7-FIB+
      LNGFR+ cells (n = 19, R = 0.719, P = 0.001). Following cell sorting, 15% of these
      cells were clonogenic. The same cells were enriched using LNGFR-based positive
      selection, CD45/Glycophorin A-based depletion, or plastic adherence. CD45low D7
      FIB+ LNGFR+ cells expressed classic makers of cultured MSCs CD73/SH3 and
      CD105/SH2 and markers of stromal reticular cells CD106/VCAM and alkaline
      phosphatase. Novel markers were identified including leukemia inhibitory factor
      receptor and gp130. CD45low D7-FIB+ LNGFR+ cells were increased fourfold in the
      floating fat fraction of normal BM aspirates. Their frequency was decreased in
      chronic lymphocytic leukemia (threefold, n = 13, P = 0.049) and chronic
      myelogenous leukemia (ninefold, n = 11, P = 0.001) compared with that in age
      matched controls (n = 26 and n = 31, respectively). CONCLUSIONS: This study
      demonstrates the usefulness of flow cytometry-based methods for the detection,
      enumeration and further phenotypic analysis of BM MSCs. These findings have broad
      applications for the future evaluation of BM MSCs in health and disease.

PMID- 16977638
TI  - Adherence to "Doing-the-month" practices is associated with fewer physical and
      depressive symptoms among postpartum women in Taiwan.
AB  - According to traditional Chinese custom, women should be confined to home and
      assisted with tasks for 1 month after giving birth to a child. This restrictive
      regimen is referred to as doing-the-month. The objectives of this study were to
      describe adherence to doing-the-month practices and to explore the association
      between adherence to doing-the-month practices and physical symptoms and
      depression among postpartum women in Taiwan. Participants were 202 women at 4-6
      weeks after delivery. Adherence to doing-the-month practices was associated with
      lower severity of physical symptoms and lower odds of postnatal depression, after
      adjustment for potential confounders. Adherence to doing-the-month practices was
      associated with better health status among postpartum women in Taiwan.

PMID- 16977639
TI  - Responding to sexual assault victims' medical and emotional needs: a national
      study of the services provided by SANE programs.
AB  - We measured the consistency with which a national random sample of 110 Sexual
      Assault Nurse Examiner (SANE) programs provided 17 services to sexual assault
      victims. SANE programs consistently offered forensic evidence collection,
      sexually transmitted infection (STI) prophylaxis, information on HIV, information
      on pregnancy risk, and referrals to community resources. Reasons programs did not
      routinely offer particular services (e.g., STI cultures, HIV testing/prophylaxis,
      emergency contraception (EC)) included financial constraints, difficulties
      balancing medical care with legal prosecution, and affiliations with Catholic
      hospitals.

PMID- 16977640
TI  - Gynecological health impact of sexual assault.
AB  - We examined the relationship between sexual assault and gynecological health
      symptoms (e.g., pelvic pain, painful intercourse) in a sample of predominately
      African American female veterans. Those who had been sexually victimized
      experienced significantly more frequent gynecological health symptoms than those
      who had not been assaulted. Multiple forced penetrations, assault by an intimate
      partner, having weapons used, physical injury, belief that the victim's life was
      in danger during the assault, and serving in the military at the time of assault
      increased the likelihood of reporting particular gynecological health symptoms.
      Screening women in health care settings for a history of violence can link women
      to resources and treatment for assault-related health symptoms.

PMID- 16977641
TI  - Implementation and effects of an individual stress management intervention for
      family caregivers of an elderly relative living at home: a mixed research design.
AB  - The purpose of this project was to evaluate the implementation and effects of a
      stress management intervention for family caregivers of elderly persons. The
      intervention was implemented through an action research design with the
      collaboration of case managers working in community health centers. A total of 81
      caregivers participated in the study. The quasi-experimental design used to test
      the effects of the intervention showed significant effects on perceived challenge
      associated with caregiver role, control by self, use of social support, and use
      of problem solving. Qualitative data demonstrate caregiver empowerment with
      respect to the caregiving role. This study illustrates the relevance of using a
      mixed research design in order to provide evidence for changes in practice.

PMID- 16977642
TI  - Effect of guided imagery with relaxation on health-related quality of life in
      older women with osteoarthritis.
AB  - Osteoarthritis (OA) is the most common cause of disability in older adults,
      which, in turn, leads to poor quality of life (QOL). Disability is caused
      primarily by the joint degeneration and pain associated with OA. A randomized
      pilot study was conducted to test the effectiveness of guided imagery with
      relaxation (GIR) to improve health-related QOL (HRQOL) in women with OA. A two
      group (intervention versus control) longitudinal design was used to determine
      whether GIR leads to better HRQOL in these individuals and whether improvement in
      HRQOL could be attributed to intervention-associated improvements in pain and
      mobility. Twenty-eight women were randomized to either the GIR intervention or
      the control intervention group. Using GIR for 12 weeks significantly increased
      women's HRQOL in comparison to the women who used the control intervention, even
      after statistically adjusting for changes in pain and mobility. These findings
      suggest that the effects of GIR on HRQOL are not limited to improvements in pain
      and mobility. GIR may be an easy-to-use self-management intervention to improve
      the QOL of older adults with OA.

PMID- 16977643
TI  - Fatigue representations in women with heart failure.
AB  - Self-care management of symptoms for persons with heart failure (HF) may only be
      successful when their representations regarding their symptoms are accurate and
      linked to appropriate behavioral strategies. The purpose of this secondary data
      analysis (N = 169 women with HF) was to describe representations of one HF
      related symptom, fatigue, and examine whether representations were related to
      physical health status, health care utilization, and psychological well-being and
      whether they differed by age. Overall, women agreed that fatigue was chronic,
      caused by HF, and had serious consequences. Midlife women reported more emotional
      distress and severe consequences from fatigue than older women. Higher levels of
      emotional distress due to fatigue from HF were associated with higher levels of
      health care utilization.

PMID- 16977644
TI  - The health care relationship (HCR) trust scale: development and psychometric
      evaluation.
AB  - A sequential multi-method approach using focus groups, individual interviews, and
      quantitative instrument development procedures was used to develop and evaluate a
      scale to measure patient trust in health care providers (HCPs). The resulting 15
      item Health Care Relationship (HCR) Trust Scale was tested for internal
      consistency, test-retest reliability, and construct validity. The Cronbach alphas
      were .92 (time 1) and .95 (time 2), respectively. Test-retest reliability was .59
      (p < .01). The HCR Trust Scale did not correlate with the Marlowe-Crowne Social
      Desirability Scale (r = .20, p = .07) or the Rapid Estimate of Adult Literacy in
      Medicine scale (r = -.21, p = .13). Principal component factor analysis with
      varimax rotation revealed a three-factor solution that explained 69% of the
      estimated common variance in the HCR trust scale. Cronbach alphas for the 3
      factors ranged from .81 to .89. Findings of this study support the use of the HCR
      Trust Scale for measuring trust in various HCPs by diverse patient populations.
      More work is needed to test the usefulness of the scale with a greater number of
      patients and in other chronic illness populations.

PMID- 16977645
TI  - Differential attrition in a caregiver skill training trial.
AB  - Participant attrition in randomized trials can reduce statistical power and bias
      outcomes. However, elective withdrawals are seldom discussed in trial reports. We
      examined factors associated with elective withdrawals for the first 131
      Alzheimer's disease (AD) and Parkinson's disease (PD) caregiver participants that
      entered Project ASSIST (Assistance, Support and Self-health Initiated through
      Skill Training), an on-going trial of caregiver skill training interventions.
      After 20 months of recruitment, 14 (11%) of the 131 ASSIST participants had
      electively withdrawn before completing the final assessment. Survival analysis
      demonstrated AD caregivers and non-spousal caregivers dropped out earlier than PD
      and spousal caregivers, even after controlling for selected baseline covariates.
      Findings suggest caregiver trial contact strategies may need to be tailored to
      retain different caregiver groups.

PMID- 16977646
TI  - The content validity index: are you sure you know what's being reported? Critique
      and recommendations.
AB  - Scale developers often provide evidence of content validity by computing a
      content validity index (CVI), using ratings of item relevance by content experts.
      We analyzed how nurse researchers have defined and calculated the CVI, and found
      considerable consistency for item-level CVIs (I-CVIs). However, there are two
      alternative, but unacknowledged, methods of computing the scale-level index (S
      CVI). One method requires universal agreement among experts, but a less
      conservative method averages the item-level CVIs. Using backward inference with a
      purposive sample of scale development studies, we found that both methods are
      being used by nurse researchers, although it was not always possible to infer the
      calculation method. The two approaches can lead to different values, making it
      risky to draw conclusions about content validity. Scale developers should
      indicate which method was used to provide readers with interpretable content
      validity information.

PMID- 16977647
TI  - Quantifying work-family conflict among registered nurses.
AB  - Work-family conflict is challenging for nurses and the nursing profession. Still
      unclear is how frequently nurses experience work-family conflict and which nurses
      experience it most frequently. We document the prevalence and frequency of work
      family conflict and describe the demographic predictors of frequent work-family
      conflict. Nurses reported greater work interference with family than family
      interference with work. Fifty percent of nurses reported chronic work
      interference with family (occurring at least once a week); another 41% reported
      episodic work interference with family (occurring less than 1-3 days per month).
      In contrast, 52% of nurses reported episodic family interference with work, and
      11% reported chronic family interference with work. Few demographic
      characteristics predicted either work interference with family or family
      interference with work.

PMID- 16977648
TI  - Resident care needs and work stressors in special care units versus non
      specialized long-term care units.
AB  - Differences in how elderly residents' care needs affect staff's experiences of
      work stressors between special care units (SCUs) for dementia and psychiatric
      residents and non-SCUs were investigated. The data were drawn from 390 staff
      members in 38 long-term care SCUs, and 587 staff in 53 non-SCUs in Finland.
      Residents' care needs were based on the Resident Assessment Instrument (RAI)
      system measured by the Minimum Data Set 2.0. Work stressors (time-pressure and
      role-conflicts) were assessed with a staff survey questionnaire. Multiple-group
      regression analysis showed that residents' dependency in activities of daily
      living (ADL) was related to increased work stressors only in SCUs. A high
      proportion of behavioral problems was related to fewer work stressors for SCU
      staff, but more for non-SCU staff. Work stressors may be reduced by specializing,
      so that residents with similar care needs are placed together and care is
      focused.

PMID- 16977649
TI  - Divide and conquer: avoiding duplication in the reporting of qualitative
      research.

PMID- 16977650
TI  - Predictors of invasion in patients with core-needle biopsy-diagnosed ductal
      carcinoma in situ and recommendations for a selective approach to sentinel lymph
      node biopsy in ductal carcinoma in situ.
AB  - BACKGROUND: Among patients with core-needle biopsy (CNB)-diagnosed ductal
      carcinoma in situ (DCIS), the guidelines for the selection of patients to undergo
      sentinel lymph node (SLN) biopsy are not well defined, and many patients with no
      invasion undergo an unnecessary SLN biopsy. The objective of this study was to
      identify the predictors of invasion in patients with CNB-diagnosed DCIS and,
      thus, to help determine the most appropriate candidates for SLN biopsy. METHODS:
      The authors retrospectively evaluated 200 consecutive patients with CNB-diagnosed
      DCIS who underwent final excision at their institution between May 1, 2002 and
      June 30, 2005. Demographic data, the size and type of lesion on imaging studies,
      histologic features of DCIS on CNB, the number of cores taken, and the number of
      cores involved by DCIS were correlated with invasion on excision and SLN biopsy
      outcome. RESULTS: Forty-one of 200 patients (21%) had invasive carcinoma
      diagnosed on final excision. Parameters that correlated with invasion were a mass
      lesion, lesion size >1.5 cm, high nuclear grade, and the presence of lobular
      cancerization on CNB. A multivariate logistic regression model was developed to
      predict invasion. At the time of breast surgery, 103 of 200 patients (52%)
      underwent SLN biopsy, and 34 had invasion diagnosed on final excision. Three
      patients had 1 positive SLN each. CONCLUSIONS: A mass lesion, lesion size >1.5
      cm, and the presence of lobular cancerization on CNB were significant,
      independent predictors of invasion in patients with DCIS. The authors recommended
      the inclusion of these predictors in the guidelines for selecting patients for
      SLN biopsy to reduce the number of unnecessary procedures.

PMID- 16977651
TI  - Antibiotic prophylaxis in neutropenic patients: new evidence, practical
      decisions.
AB  - New evidence shows that antibiotic prophylaxis in neutropenic patients reduces
      mortality, febrile episodes, and bacterial infections. For patients with acute
      leukemia or those who undergo bone marrow transplantation, prophylaxis with
      fluoroquinolones diminished the risk of death from any cause by 33% (95%
      confidence interval [95% CI], 2-54%). Thus, 55 patients who have acute leukemia
      or who undergo bone marrow transplantation must receive prophylaxis to prevent 1
      death. In 4 studies that included patients with solid tumors or lymphoma,
      prophylaxis reduced the rate of death during the first month (relative risk,
      0.51; 95% CI, 0.27-0.97), and 82 patients had to receive prophylaxis to prevent 1
      death. The main argument brought against prophylaxis is the induction of
      resistance. Patients who received prophylaxis did not experience more infections
      caused by resistant strains than patients in the control group. The recent GIMEMA
      study was conducted in a population with a nearly 50% resistance to
      fluoroquinolones in all pathogens and 20% resistance in gram-negative isolates,
      thus indicating that prophylaxis should be offered in settings with similar or
      less resistance. Prophylaxis with fluoroquinolones was efficacious in reducing
      infections caused by gram-positive bacteria. Patients who are treated for acute
      leukemia should be offered prophylaxis with ciprofloxacin or levofloxacin.
      Prophylaxis to cover the expected period of neutropenia may be considered for the
      first cycle of treatment in patients with solid tumors or lymphoma who regularly
      receive regimens that cause severe neutropenia. Excessive local levels of
      resistance to fluoroquinolones or high local incidence of infections caused by
      Clostridium difficile and related to fluoroquinolones should prompt a
      reconsideration of this policy.

PMID- 16977652
TI  - The European Organization for Research and Treatment of Cancer (EORTC) Quality-of
      Life questionnaire cervical cancer module: EORTC QLQ-CX24.
AB  - BACKGROUND: The authors report on the development and validation of a cervical
      cancer module for the European Organization for Research and Treatment of Cancer
      (EORTC) Quality-of-Life (QoL) questionnaire (QLQ), which was designed to assess
      disease-specific and treatment-specific aspects of QoL in patients with cervical
      cancer. METHODS: The cervical cancer module (EORTC QLQ-CX24) was developed in a
      multicultural, multidisciplinary setting to supplement the EORTC QLQ-C30 core
      questionnaire. The QLQ-C30 and the cervical cancer module were administered to
      346 patients with cervical cancer who underwent radical hysterectomy and received
      radiotherapy and chemotherapy. Psychometric analyses were performed by using data
      from 2 independent samples. RESULTS: The QLQ-CX24 consists of 3 multiitem scales
      and 5 single-item scales. Multitrait scaling analyses revealed high internal
      consistencies for the subscales with Cronbach alpha coefficients ranging from .72
      to .87 (Symptom Experience, .72; Body Image, .86; Sexual/Vaginal Functioning,
      .87). Convergent and discriminant validity were fulfilled with scaling errors
      below 3%. The QLQ-CX24 was capable of discriminating between clinical subgroups.
      All items exhibited good compliance with <3% missing values. Most patients
      completed the EORTC QLQ-C30 and the QLQ-CX24 in <15 minutes (86%), and many did
      not require any assistance to complete the questionnaires (65%). CONCLUSIONS: The
      current psychometric analyses supported the content and construct validity and
      the reliability of the EORTC QLQ-CX24 module. This newly developed module is a
      useful instrument for assessing the QoL of patients who are treated for cervical
      cancer both in clinical trials and in clinical practice.

PMID- 16977653
TI  - Therapeutic role of lymph node resection in endometrioid corpus cancer: a study
      of 12,333 patients.
AB  - BACKGROUND: The purpose of the current study was to determine the potential
      therapeutic role of lymphadenectomy in women with endometrioid corpus cancer.
      METHODS: Demographic and clinicopathologic information were obtained from the
      Surveillance, Epidemiology, and End Results Program between 1988-2001. Data were
      analyzed using Kaplan-Meier methods and Cox proportional hazards regression.
      RESULTS: In all, 12,333 women (median age, 64) underwent surgical staging with
      lymph node assessment, including 9,009, 1,211, 1,223, and 890 with Stage I-IV
      disease. Over the time intervals 1988-1992, 1993-1997, and 1998-2001, the
      percentage of patients undergoing lymph node staging increased from 22.6%, 29.6%,
      to 40.9% (P < .001). In the intermediate/high-risk patients (Stage IB, Grade 3;
      Stage IC and II-IV, all grades), a more extensive lymph node resection (1, 2-5, 6
      10, 11-20, and >20) was associated with improved 5-year disease-specific
      survivals across all 5 groups at 75.3%, 81.5%, 84.1%, 85.3%, and 86.8%,
      respectively (P < .001). For Stage IIIC-IV patients with nodal disease, the
      extent of node resection significantly improved the survival from 51.0%, 53.0%,
      53.0%, 60.0%, to 72.0%, (P < .001). However, no significant benefit of lymph node
      resection in low-risk patients could be demonstrated (Stage IA, all grades; Stage
      IB, Grades 1 and 2 disease; P = .23). In multivariate analysis, a more extensive
      node resection remained a significant prognostic factor for improved survival in
      intermediate/high-risk patients after adjusting for other factors including age,
      year of diagnosis, stage, grade, adjuvant radiotherapy, and the presence of
      positive nodes (P < .001). CONCLUSIONS: The findings of the current study suggest
      that the extent of lymph node resection improves the survival of women with
      intermediate/high-risk endometrioid uterine cancer.

PMID- 16977654
TI  - Quality-of-life and health benefits of early treatment of mild anemia: a
      randomized trial of epoetin alfa in patients receiving chemotherapy for
      hematologic malignancies.
AB  - BACKGROUND: Chemotherapy-related anemia is prevalent among patients with
      hematologic malignancies. A randomized, open-label, multicenter trial of early
      versus late epoetin alfa in this population was conducted, focusing on quality of
      life (QOL). METHODS: Patients with non-Hodgkin lymphoma, Hodgkin lymphoma,
      chronic lymphocytic leukemia, or multiple myeloma and baseline hemoglobin of 10
      to 12 g/dL who were scheduled for > or = 4 months of myelosuppressive
      chemotherapy were randomized to receive < or = 16 weeks of epoetin alfa at a dose
      of 40,000 U once weekly immediately (early) or to wait and only receive epoetin
      alfa if hemoglobin decreased to < 9 g/dL (late). Those patients with a hemoglobin
      level > 12 g/dL after 3 chemotherapy cycles were not randomized. The primary
      endpoint was a mean change in the Functional Assessment of Cancer Therapy-Anemia
      (FACT-An) total. RESULTS: In all, 269 patients with a hemoglobin level < or = 12
      g/dL were randomized. The mean total FACT-An increased 3.84 (95% confidence
      interval [95% CI], 0.21-7.46) in early patients and decreased 4.37 (95% CI, -7.99
      to -0.74) in late patients (P = .003). Early patients had significantly (P < .05)
      higher mean scores for total FACT-General; FACT-General physical and functional
      well-being subscales, total anemia scale, and fatigue subscale; and daily
      activity, energy, and important activity Linear Analog Scale Assessment scales,
      as well as reduced bedrest days and restricted activity days. The mean hemoglobin
      increased 1.2 g/dL (95% CI, 0.98-1.46) in early patients but decreased 0.2 g/dL
      (95% CI, -0.32-0.12) in late patients (P < .0001). Adverse events were similar
      between groups (with fatigue being the most prevalent); clinically relevant
      thromboembolic events were more common in early patients. CONCLUSIONS: Treating
      mild anemia immediately with epoetin alfa during chemotherapy for hematologic
      malignancy significantly improved QOL, productivity, and hemoglobin compared with
      delaying treatment until the hemoglobin level decreases to < 9.0 g/dL.

PMID- 16977655
TI  - An approach for a synthesis of asparagine-linked sialylglycopeptides having
      intact and homogeneous complex-type undecadisialyloligosaccharides.
AB  - This paper describes synthesis of asparagine-linked sialylglycopeptides. The
      typical feature of our strategy for the synthesis of a sialylglycopeptide is to
      employ undecadisialyloligosaccharyl Fmoc-asparagine (Fmoc-Asn(CHO)-OH) 1 without
      protecting groups on its hydroxyl groups except for the benzyl ester of the NeuAc
      residues. Our synthetic methodology solved the problem of esterification toward
      sugar hydroxyl groups by activated amino acids during the elongation of a peptide
      chain. When employing high concentrations of the Fmoc-amino acid, esterification
      markedly occurred, but the esterification scarcely occurred when employing low
      concentrations of reactants. Taking advantage of these findings, we examined the
      synthesis of a high molecular sialylglycopeptide, CTLA-4 fragment (113-150) 13
      having two complex-type sialyloligosaccharides by use of native chemical ligation
      (NCL). As a result, we succeeded in the synthesis of a sialylglycopeptide having
      a cysteine residue at the N-terminus (CTLA-4: 129-150 fragment) 11 and a
      sialylglycopeptide-thioester (CTLA-4: 113-128 fragment) 12. Finally, the
      sialylglycopeptides synthesized were applied to NCL reactions. The reaction
      successfully afforded the desired product, CTLA-4 (113-150) 13 containing mature
      and pure complex-type sialyloligosaccharides in excellent purity.

PMID- 16977656
TI  - A square-planar organoiron(III) compound with a spin-admixed state.

PMID- 16977658
TI  - Dynamical behavior and dipole-dipole interactions of tetrafluoromethane-water.

PMID- 16977657
TI  - Total synthesis of marinomycins A-C.

PMID- 16977659
TI  - Colorimetric identification of carbohydrates by a pH indicator/pH change inducer
      ensemble.

PMID- 16977660
TI  - Diels-Alder approach to polysubstituted biaryls: rapid entry to tri- and tetra
      ortho-substituted phosphorus-containing biaryls.

PMID- 16977661
TI  - Mutational studies confirm the catalytic triad in the human selenoenzyme
      thioredoxin reductase predicted by molecular modeling.

PMID- 16977662
TI  - Water exclusion and enantioselectivity in catalysis.

PMID- 16977663
TI  - Leucyl/Phenylalanyl-tRNA-protein transferase-mediated chemoenzymatic coupling of
      N-terminal Arg/Lys units in post-translationally processed proteins with non
      natural amino acids.

PMID- 16977664
TI  - Na2Li8[(UO2)11O12(WO5)2]: Three different uranyl-ion coordination geometries and
      cation-cation interactions.

PMID- 16977665
TI  - Hydroxy-substituted oligosilane dendrimers: controlling the electronic properties
      through hydrogen bonding.

PMID- 16977666
TI  - The reaction of hydrogen atoms with methionine residues: A model of reductive
      radical stress causing tandem protein-lipid damage.
AB  - The occurrence of tandem damage, due to reductive radical stress involving
      proteins and lipids, is shown by using a biomimetic model. It is made of
      unsaturated lipid vesicle suspensions in phosphate buffer in the presence of
      methionine, either as a single amino acid or as part of a protein such as RNase
      A, which contains four methionine residues. The radical process starts with the
      formation of H(.) atoms by reaction of solvated electrons with dihydrogen
      phosphate anions, which selectively attack the thioether function of methionine.
      The modification of methionine to alpha-aminobutyric acid is accompanied by the
      formation of thiyl radicals, which in turn cause the isomerization of the cis
      fatty acid residues to the trans isomers. The relationship between methionine
      modification and lipid damage and some details of the reductive radical stress
      obtained by proteomic analysis of irradiated RNase A are presented.

PMID- 16977667
TI  - Structure-function analysis of the soluble glycoprotein, sGP, of Ebola virus.
AB  - In addition to the transmembrane protein, GP(1,2), the Ebola virus glycoprotein
      gene encodes the soluble glycoproteins sGP and Delta-peptide. Two more soluble
      proteins, GP(1) and GP(1,2DeltaTM), are generated from GP(1,2) as a result of
      disulfide-bond instability and proteolytic cleavage, respectively, and are shed
      from the surface of infected cells. The sGP glycoprotein is secreted as a
      disulfide-linked homodimer, but there have been conflicting reports on whether it
      is arranged in a parallel or antiparallel orientation. Off-line HPLC-MALDI-TOF MS
      (MS/MS) was used to identify the arrangement of all disulfide bonds and
      simultaneously determine site-specific information regarding N-glycosylation. Our
      data prove that sGP is a parallel homodimer that contains C53-C53' and C306-C306'
      disulfide bonds, and although there are six predicted N-linked carbohydrate
      sites, only five are consistently glycosylated. The disulfide bond arrangement
      was confirmed by using cysteine to glycine mutations at amino acid positions 53
      and 306. The mutants had a reduced ability to rescue the barrier function of TNF
      alpha-treated endothelial cells--a function previously reported for sGP. This
      indicates that these disulfide bonds are critical for the proposed anti
      inflammatory function of sGP.

PMID- 16977668
TI  - The solution structure of stilbenoid dendrimers: a small-angle scattering study.
AB  - The spatial structure of a stilbenoid dendrimer is investigated by small-angle X
      ray scattering (SAXS) and small-angle neutron scattering (SANS) in dilute
      solution. All measurements are performed in toluene. The dendrimer consists of a
      stilbenoid scaffold with appended hexyloxy chains. SAXS is mainly sensitive to
      the dendrimer scaffold whereas SANS intensity, measured in fully deuterated
      toluene, derives from the solute molecules. The resulting SAXS and SANS
      intensities are analyzed by comparison with various models. It is found that the
      model of a circular disk gives the best description of the data. SAXS data
      demonstrate that the stilbenoid scaffold is flat as expected for benzene rings
      conjugated through vinylene units. Thus, it can be described by a circular disk
      with a radius of 1.6 nm and a thickness of 0.7 nm. SANS, on the other hand, shows
      that the hexyloxy chains are not confined in the plane defined by the core. This
      is derived from modeling the SANS data with a much thicker circular disk (radius:
      2.4 nm, thickness: 1.8 nm). The structure factor S(q), describing the interaction
      of the dendrimers at higher concentrations, is modeled quantitatively with the
      "polymer reference interaction site model" (PRISM) integral equation formalism
      for hard plates such as particles. Here the structural data obtained from the
      analysis of the SANS data are used so that no new adjustable parameter is
      necessary for this description.

PMID- 16977669
TI  - Efficient charge injection from the S2 photoexcited state of special-pair mimic
      porphyrin assemblies anchored on a titanium-modified ITO anode.
AB  - A novel surface fabrication methodology has been accomplished, aimed at efficient
      anodic photocurrent generation by a photoexcited porphyrin on an ITO (indium-tin
      oxide) electrode. The ITO electrode was submitted to a surface sol-gel process
      with titanium n-butoxide in order to deposit a titanium monolayer. Subsequently,
      porphyrins were assembled as monolayers on the titanium-treated ITO surface via
      phosphonate, isophthalate, and thiolate groups. Slipped-cofacial porphyrin
      dimers, the so-called artificial special pair at the photoreaction center, were
      organized through imidazolyl-to-zinc complementary coordination of
      imidazolylporphyrinatozinc(II) units, which were covalently immobilized by ring
      closing olefin metathesis of allyl side chains. The modified surfaces were
      analyzed by means of X-ray photoelectron spectroscopy. Photoirradiation of the
      porphyrin dimer generated a large anodic photocurrent in aqueous electrolyte
      solution containing hydroquinone as an electron sacrificer, due to the small
      reorganization energy of the dimer. The use of different linker groups led to
      significant differences in the efficiencies of anodic photocurrent generation.
      The apparent flat-band potentials evaluated from the photocurrent properties at
      various pH values and under biased conditions imply that the band structure of
      the ITO electrode is modified by the anchoring species. The quantum yield for the
      anodic photocurrent generation by photoexcitation at the Soret band is increased
      to 15 %, a surprisingly high value without a redox cascade structure on the ITO
      electrode surface, while excitation at the Q band is not so significant.
      Extensive exploration of the photocurrent properties has revealed that hot
      injection of the photoexcited electron from the S2 level into the conduction band
      of the ITO electrode takes place before internal conversion to the S1* state,
      through the strong electronic communication of the phosphonyl anchor with the sol
      gel-modified ITO surface.

PMID- 16977670
TI  - Preparation, purification, characterization, and cytotoxicity assessment of water
      soluble, transition-metal-free carbon nanotube aggregates.

PMID- 16977671
TI  - (Ca7N4)[Mx] (M=Ag, Ga, In, Tl): linear metal chains as guests in a subnitride
      host.

PMID- 16977672
TI  - The feasibility of a GP led screening intervention for depression among nursing
      home residents.
AB  - AIM: To examine the feasibility of a brief intervention training general
      practitioners (GPs) in the administration of a depression screening instrument
      for use among nursing home residents. INTERVENTION: GPs attended a single
      education session on late-life depression and were trained in the use of the
      Cornell Scale for Depression in Dementia. Following the intervention GPs reviewed
      their patients for depression. OUTCOME MEASURES: Diagnosis of depression pre and
      post intervention; changes in antidepressant medications post intervention.
      RESULTS: Ten GPs and 38 patients completed all components of the study. GPs
      identified that 24% of their patients had Cornell Scores indicative of probable
      major depression that was either unrecognised or inadequately treated. 88% of
      these patients had been previously diagnosed with depression. A further 32% of
      patients exhibited depression symptoms, half (50%) of whom had a previous
      diagnosis of depression. Reviewing patients had an effect on antidepressant
      prescribing for patients with probable major depression, with GPs making changes
      to the antidepressant medication of 29% of patients. CONCLUSIONS: The high rate
      of residents presenting with probable major depression despite being prescribed
      antidepressants indicate that depression symptoms are inadequately recognised and
      treated in nursing homes. This study demonstrated that a single education session
      on late-life depression was feasible and was associated with an improvement in
      GPs' recognition of depression among nursing home patients.

PMID- 16977673
TI  - The Addenbrooke's Cognitive Examination Revised (ACE-R): a brief cognitive test
      battery for dementia screening.
AB  - There is a clear need for brief, but sensitive and specific, cognitive screening
      instruments as evidenced by the popularity of the Addenbrooke's Cognitive
      Examination (ACE). OBJECTIVES: We aimed to validate an improved revision (the ACE
      R) which incorporates five sub-domain scores (orientation/attention, memory,
      verbal fluency, language and visuo-spatial). METHODS: Standard tests for
      evaluating dementia screening tests were applied. A total of 241 subjects
      participated in this study (Alzheimer's disease=67, frontotemporal dementia=55,
      dementia of Lewy Bodies=20; mild cognitive impairment-MCI=36; controls=63).
      RESULTS: Reliability of the ACE-R was very good (alpha coefficient=0.8).
      Correlation with the Clinical Dementia Scale was significant (r=-0.321, p<0.001).
      Two cut-offs were defined (88: sensitivity=0.94, specificity=0.89; 82:
      sensitivity=0.84, specificity=1.0). Likelihood ratios of dementia were generated
      for scores between 88 and 82: at a cut-off of 82 the likelihood of dementia is
      100:1. A comparison of individual age and education matched groups of MCI, AD and
      controls placed the MCI group performance between controls and AD and revealed
      MCI patients to be impaired in areas other than memory (attention/orientation,
      verbal fluency and language). CONCLUSIONS: The ACE-R accomplishes standards of a
      valid dementia screening test, sensitive to early cognitive dysfunction.

PMID- 16977674
TI  - Dehydroepiandrosterone sulfate (DHEA-S) and Alzheimer's dementia in older
      subjects.
AB  - OBJECTIVES AND METHODS: We investigated the association of serum
      dehydroepiandrosterone sulfate (DHEA-S) levels with dementia of Alzheimer's type
      (DAT) and impairment in selected cognitive domains (memory, language, attention
      and working memory) in 158 patients (75.5+/-6.7 years, 46 men) with first
      diagnosed probable DAT and in 158 age- and sex-matched controls. As secondary
      goal, we evaluated whether DHEA-S baseline levels were associated with cumulative
      6-year mortality. RESULTS: A negative correlation between DHEA-S levels and age
      was observed (R=-0.25, p<0.001). Age-stratified analysis did not show significant
      differences of DHEA-S levels between DAT patients and controls. No significant
      association was found between DHEA-S levels and impairment in selected cognitive
      domains. Cox regression analysis showed that baseline DHEA-S levels were not
      associated with cumulative 6-year mortality. CONCLUSIONS: In a sample of newly
      diagnosed DAT patients, we did not find significant association between presence
      of DAT or impairment in cognitive domains and DHEA-S levels; baseline DHEA-S
      levels are not associated with cumulative mortality in patients and controls.

PMID- 16977675
TI  - Dementia and depression among nursing home residents in Lebanon: a pilot study.
AB  - BACKGROUND: The proportion of elderly in the Lebanese population is 7.1% and this
      is expected to increase to 10.2% by the year 2025. The nursing home (NH)
      population in Lebanon has not been studied. The aim of this study was to
      investigate the prevalence of dementia and depression among a portion of nursing
      home residents (NHR) in Lebanon and describe the characteristics of NHR afflicted
      with dementia and depression. METHOD: Of 200 NHR from three NH in Lebanon, 117
      were selected by random sampling. Data on demographics and medical history were
      collected. An Arabic version of the Mini-Mental Status Examination and Geriatric
      Depression Scale (GDS) were administered. RESULTS: Our final sample consisted of
      102 NHR. Sixty-one (59.8%) had dementia of some kind. Seventeen (27.9%) had mild
      dementia, 14 (22.9%) had moderate dementia, and 30 (49.2%) had severe dementia.
      Forty-five (57.7%) of the NHR tested had depression as measured by a GDS score of
      more than 10. CONCLUSIONS: Dementia and depression were present in more than half
      of the NHR in our sample. Our results have important implications, being the
      first to be collected in the Lebanese community. Screening NHR for dementia and
      depression on admission and at regular time intervals is a must. More studies
      targeting all aspects of the elderly population in Lebanon are needed.

PMID- 16977676
TI  - Humour therapy in patients with late-life depression or Alzheimer's disease: a
      pilot study.
AB  - BACKGROUND: Of the disabling disorders of the elderly, depression is the most
      common affective disorder and Alzheimer's disease (AD) the most common
      neurodegenerative disorder. Pharmacological treatment strategies for these
      disorders are often accompanied with severe side effects. Therefore non
      pharmacological treatment strategies are of great importance. The aim of the
      present study was to investigate the impact of humour therapy on quality of life
      in patients with depression or AD. METHODS: Twenty patients with late-life
      depression and 20 patients with AD were evaluated. Ten patients in each group
      underwent a humour therapy group (HT) once in two weeks for 60 min in addition to
      standard pharmacotherapy, which was given as usual to the other group as standard
      therapy (ST). All patients completed a psychometric test battery at admission and
      before discharge from the clinic. RESULTS: The quality of life scores improved
      both in HT and ST groups for depressive patients but not for patients with AD
      irrespective of the therapy group. Depressive patients receiving HT showed the
      highest quality of life after treatment. In addition, patients with depression in
      both therapy groups showed improvements in mood, depression score, and
      instrumental activities of daily living. CONCLUSIONS: Although there was no
      significant effect of humour therapy comparing with standard therapy on quality
      of life, these findings suggest that humour therapy can provide an additional
      therapeutic tool. Further studies with higher frequently humour groups are
      required in order to investigate the impact of humour therapy in
      gerontopsychiatric treatment.

PMID- 16977677
TI  - GP concordance with advice for treatment following a multidisciplinary
      psychogeriatric assessment.
AB  - OBJECTIVE: To evaluate the concordance of General Practitioners (GPs) with advice
      for treatment after a multidisciplinary psychogeriatric assessment by the
      Diagnostic Observation Centre for PsychoGeriatric patients (DOC-PG). METHOD:
      Concordance checklists, listing the recommendations from the multidisciplinary
      team, were sent to the GPs in order to establish GP concordance. Regression
      models were used to study the associations between various patient and GP
      characteristics and level of concordance. Furthermore, results of a questionnaire
      (to identify the level of satisfaction regarding the services provided by the DOC
      PG) were compared with the level of GP concordance. RESULTS: Based on 530
      recommendations, the overall GP concordance rate amounted to 71%. The most common
      types of advice pertained to medication, GP follow-up/advice and referral. GP
      concordance with advice regarding admissions was the highest, followed by advice
      concerning the arrangement of daycare, home care and the adaptation of
      medication. GP concordance was lowest for referral recommendations to other
      specialties and recommendations regarding psychoeducation. Concordance was higher
      for patients who lived alone, for patients with fewer cognitive problems, when
      the number of recommendations did not exceed six and in group practices.
      Concordance was dependent on the type of advice. Satisfaction with DOC-PG did not
      correlate with the level of concordance. CONCLUSIONS: In general, GPs showed a
      high level of concordance with advice from the DOC-PG. Enhancement of GP
      concordance can be achieved by limiting the number of recommendations, giving
      detailed explanations about the purpose of recommendations and educating GPs by
      doing.

PMID- 16977679
TI  - Rates and previous disease history in old age suicide.
AB  - OBJECTIVE: Suicide rates in persons over 65 have been reported to be higher than
      those of younger age groups. Since the absolute number of suicides in the elderly
      is expected to rise, more precise ways to identify potential risk factors for
      elderly suicides are needed. METHODS: On the basis of forensic examinations
      suicide rates and methods in elderly Finns of northern Finland were compared with
      those of adults aged 18-64 years. Data from earlier illnesses of the suicide
      victims were scrutinized for records of multiple physical disorders. RESULTS:
      Over the 15-year period the mean annual suicide rate per population of 100,000
      was significantly lower in the elderly (22.5) than adults aged 18-64 years
      (38.4). A decrease in suicide rates over time occurred in both groups. Suicide
      methods among elderly were more often violent, and they were seldom under the
      influence of alcohol. They also had a high prevalence of previous hospital
      treated depressive episodes and hospital-treated physical illnesses. A lifetime
      history of hospital-treated depression was more common among elderly victims who
      had received hospital treatment for genitourinary diseases, injuries or
      poisonings after their 50th birthday. CONCLUSIONS: Our results from elderly
      suicide victims suggest an association between multiple physical illnesses and a
      history of depression. Especially, genitourinary diseases as well as hospital
      treatment due to injuries or poisonings were shown to associate with depression.
      Elderly Northern Finns showed lower suicide rates, and they decreased during the
      study period suggesting that active preventive measures against suicide are also
      feasible in the elderly.

PMID- 16977678
TI  - Do symptoms of memory impairment correspond to cognitive impairment: a cross
      sectional study of a clinical cohort.
AB  - BACKGROUND: Symptoms of memory loss are a common complaint within the general
      population and a frequent reason for seeking medical advice. However, the
      clinical relevance of these symptoms to future development of neurodegenerative
      disease is uncertain. The aim of this study is to characterise a cohort of
      individuals with symptoms of memory loss and varying memory impairment, who will
      be followed longitudinally with serial neuropsychology and neuroimaging to
      evaluate the clinical relevance of symptoms of memory loss. METHOD: Fifty-eight
      subjects with symptoms of memory loss were recruited from the National Hospital
      for Neurology and Neurosurgery. All subjects underwent clinical assessment, APOE4
      genotyping, neuroimaging and neuropsychological tests. RESULTS: Those with mild
      cognitive impairment (MCI) had an increased prevalence of the APOE4 allele,
      impaired performance on tests of memory, measures of IQ and naming compared to
      controls. Baseline brain volumes were decreased and ventricular size increased.
      Those with symptoms of memory loss but no cognitive impairment (SNCI) performed
      significantly worse on tests of memory than the control group. CONCLUSIONS: The
      MCI represent a group with multiple risk factors for progression to AD. The SNCI
      group may represent a heterogeneous group with some individuals in the early
      stages of AD whilst others' memory complaints are more likely linked to anxiety
      or personality traits.

PMID- 16977680
TI  - Do the ABCS 135 short cognitive screen and its subtests discriminate between
      normal cognition, mild cognitive impairment and dementia?
AB  - BACKGROUND: Cognitive screening instruments are either too long for routine
      clinical use or not sensitive to distinguish mild cognitive impairment (MCI) from
      normal cognition (NC) or dementia. OBJECTIVE: To evaluate the sensitivity and
      specificity of the AB Cognitive Screen (ABCS) and its subtests with a view to
      improving its ability to differentiate between dementia, MCI and NC. The
      influence of age and education on sensitivity and specificity is also examined.
      DESIGN: Cross-sectional study. METHODS: Participants with dementia and MCI were
      recruited from those presenting to four specialty geriatric clinics in southern
      Ontario. Participants with NC were recruited from the family and friends of
      patients. A comprehensive geriatric assessment was done including ABCS, SMMSE and
      15 point Geriatric Depression Scale. Analysis of variance and receiver operating
      characteristic (ROC) curves compared test scores. SMMSE scores were also analysed
      for comparison purposes. RESULTS: Three hundred and two participants had
      dementia, 166 had MCI and 174 had NC. ABCS total scores were significantly
      different between NC and MCI (mean difference 7.1, 1.8-12.5 CI, p = 0.000) while
      SMMSE scores were not (mean difference 0.5, -0.7-1.7, p < 0.628). Of individual
      ABCS subtests, verbal fluency and delayed recall were most sensitive to
      differences between NC and MCI. ROC curve analysis, which presents sensitivity
      and specificity, showed verbal fluency was better than delayed recall in
      distinguishing between NC and MCI, among participants 75 years of age or older.
      CONCLUSION: The AB Cognitive Screen (ABCS) can be administered in 3-5 min. The
      SMMSE and ABCS total and subtests significantly distinguished between dementia
      and MCI or NC. Verbal fluency and delayed recall were best at distinguishing
      between MCI and NC. The analysis illustrates how each subtest contributes to the
      sensitivity of the ABCS and suggests ways that sensitivity might be improved.

PMID- 16977681
TI  - Costs of community-based public mental health services for older adults:
      variations related to age and diagnosis.
AB  - BACKGROUND: Several studies have examined service use among older adults
      although, to our knowledge, none has examined costs from a systems perspective.
      This study examined use and costs of mental health services among older adults in
      San Diego County in order to determine how expenditures and modes of service
      varied by age cohort and psychiatric diagnosis. METHODS: Utilization data from
      San Diego County Adult and Older Adult Mental Health Services (AOAMHS) were used
      to identify older adults (age > or = 60) receiving services in the community
      during fiscal year 2003-2004. Cost data were derived from detailed examination of
      cost reports, and Medicaid fee schedules. Trends in demographic and clinical
      characteristics by six age cohorts were described. Multivariate models were used
      to estimate the relationships between costs, age, and clinical diagnosis while
      controlling for other demographic and clinical characteristics. Components of
      costs were also examined. RESULTS: Total expenditures declined from age cohorts
      60-64 through ages 85 and over. Expenditures were similar, and greatest, for
      clients with schizophrenia and bipolar disorder, while outlays were lower for
      those with major depression, other psychotic disorder, other depression, anxiety,
      substance use disorder, and cognitive disorders. Clients diagnosed with cognitive
      disorder had high use of emergency services and little connection to outpatient
      services. CONCLUSIONS: Expenditures were related to age and clinical diagnosis.
      Future efforts should investigate older adults' pathways to care, and should
      determine whether older adults presenting in emergency services would benefit
      from a specialized case management program providing linkages to community based
      resources.

PMID- 16977682
TI  - Capillary separations enabling tissue proteomics-based biomarker discovery.
AB  - Development of the capability to enable large-scale proteome studies, analogous
      to comprehensive gene expression analysis, will clearly have far-reaching impacts
      on protein biomarker investigations of human diseases such as cancer through
      interrogation of the archived fresh frozen and formalin-fixed and paraffin
      embedded tissue collections. This review therefore focuses on the most recent
      advances in microdissection techniques and proteome platforms for procuring
      homogeneous subpopulations of tumor cells or structures and performing
      comprehensive analysis of protein profiles within tissue specimens, respectively.
      Developments in capillary separations capable of providing extremely high
      resolving power and selective analyte enrichment are particularly highlighted for
      their roles within the broader context of a state-of-the-art integrated tissue
      proteome effort. The capabilities of CIEF-based multidimensional separations for
      performing proteome analysis from minute samples create new opportunities in the
      pursuit of biomarker discovery using enriched and selected cell populations
      procured from tissue specimens. These proteome technological advances combined
      with recently developed tissue microdissection techniques provide powerful tools
      for those seeking to gain a greater understanding at the global level of the
      cellular machinery associated with human diseases such as cancer.

PMID- 16977683
TI  - Transient isotachophoresis in carrier ampholyte-based capillary electrophoresis
      for protein analysis.
AB  - Transient ITP (t-ITP) has been used in carrier ampholyte-based CE (CABCE) to
      enhance the sensitivity of protein analysis. The characteristics of carrier
      ampholytes (CAs) narrow pH cuts-based buffers, when used as BGEs in CE are
      compatible with t-ITP requirements. Indeed, being the sole buffering species of
      such solutions, CAs impose a pH close to their pI. Thus, in these solutions, the
      CAs possess low electrophoretic mobility. As a consequence, by adding an ionic
      component with high electrophoretic mobility either in the studied sample or in
      the BGE, a t-ITP step can be generated. This has first been demonstrated for
      protein test mixtures. Then, the combination of t-ITP with CABCE has been applied
      to study a real sample, the bovine milk.

PMID- 16977684
TI  - SDS-CGE of proteins in microchannels made of SU-8 films.
AB  - This work describes the SDS-CGE of proteins carried out in microchannels made of
      the negative photoresist EPON SU-8. Embedded electrophoretic microchannels have
      been fabricated with a multilayer technology based on bonding and releasing steps
      of stacked SU-8 films. This technology allows the monolithic integration of the
      electrodes in the device. A high wafer fabrication yield and mass production
      compatibility guarantees low costs and high reliability. A poly(methyl
      methacrylate) (PMMA) packaging allows an easy setup and replacement of the device
      for electrophoresis experiments. In addition, the wire-bonding step is avoided.
      The electrophoretic mobilities of four proteins have been measured in
      microchannels filled with polyacrylamide. Different pore sizes have been tested
      obtaining their Ferguson plots. Finally, a separation of two proteins (20 and 36
      kDa) has been carried out confirming that this novel device is suitable for
      protein separation. A resolution of 2.75 is obtained. This is the first time that
      this SU-8 microfluidic technology has been validated for SDS-CGE of proteins.
      This technology offers better separation performance than glass channels, at
      lower costs and with an easy packaging procedure.

PMID- 16977685
TI  - A self-contained polymeric 2-DE chip system for rapid and easy analysis.
AB  - We developed a polymeric 2-DE chip system. The chip consisted of an IEF region,
      an SDS-PAGE region, a valveless connection port, and a sample introduction port.
      A "junction structure" as a valveless connection port, which allowed separating
      and connecting the first- and second-dimensional gels, was fabricated between
      their regions. A "solution inlet" as a sample introduction port was fabricated to
      perform the liquid and sample introductions without solution leakage.
      Simultaneous sample monitoring was performed using the on-chip detection system.
      The performances of the system were demonstrated using commercially available
      proteins as a standard specimen and tissue-extracted proteins as the real
      samples. All procedures were employed without any movement of relocation part.
      This new 2-D separation system realized improved labor-intensive operations and a
      reduced experimental time.

PMID- 16977689
TI  - Nonseminomatous germ cell tumor after chemotherapy with residual mass invading
      the spine: part 2.

PMID- 16977690
TI  - Echovirus 13 aseptic meningitis, Brazil.

PMID- 16977691
TI  - Echinococcus multilocularis in dogs, Japan.

PMID- 16977692
TI  - Special issue: Mechanistic approaches to chemoprevention of mutation and cancer.
      Dedicated to Giorgio Bronzetti (1939-2005).

PMID- 16977694
TI  - Selected papers from the 4th Computational Systems Bioinformatics Conference
      2005.

PMID- 16977693
TI  - Special issue in honour of Stanley J. Korsmeyer.

PMID- 16977695
TI  - Selected papers from the International Moscow Conference on Computational
      Molecular Biology 2005.

PMID- 16977696
TI  - Addressing Translational Research in Efficacy and Safety of New Medicines.
      Abstracts of the 2006 International Conference Frontiers of Pharmacology and
      Toxicology, August 28-31, 2006, Chicago, Illinois, USA.

PMID- 16977697
TI  - Functional neuroscience: evoked potentials and related techniques. Selected
      presentations from the 8th International Evoked Potentials Symposium. Fukuoka,
      Japan.

PMID- 16977699
TI  - Life is degrading--thanks to some zomes.
AB  - Three structurally related protein complexes, the COP9 signalosome, the
      proteasome lid, and the eukaryotic translation initiation factor 3, are revealing
      new insights into developmental processes and into cell cycle control in healthy
      cells and cells exposed to genotoxic stress. Newly discovered cullin-RING E3
      ubiquitin ligases assembled on the CUL4 platform may provide links between DNA
      replication, chromatin, and proteolysis.

PMID- 16977698
TI  - Computational detection of allergenic proteins attains a new level of accuracy
      with in silico variable-length peptide extraction and machine learning.
AB  - The placing of novel or new-in-the-context proteins on the market, appearing in
      genetically modified foods, certain bio-pharmaceuticals and some household
      products leads to human exposure to proteins that may elicit allergic responses.
      Accurate methods to detect allergens are therefore necessary to ensure
      consumer/patient safety. We demonstrate that it is possible to reach a new level
      of accuracy in computational detection of allergenic proteins by presenting a
      novel detector, Detection based on Filtered Length-adjusted Allergen Peptides
      (DFLAP). The DFLAP algorithm extracts variable length allergen sequence fragments
      and employs modern machine learning techniques in the form of a support vector
      machine. In particular, this new detector shows hitherto unmatched specificity
      when challenged to the Swiss-Prot repository without appreciable loss of
      sensitivity. DFLAP is also the first reported detector that successfully
      discriminates between allergens and non-allergens occurring in protein families
      known to hold both categories. Allergenicity assessment for specific protein
      sequences of interest using DFLAP is possible via ulfh@slv.se.

PMID- 16977700
TI  - Cyclophosphamide in scleroderma lung disease.

PMID- 16977701
TI  - Cyclophosphamide in scleroderma lung disease.

PMID- 16977702
TI  - Fluid-management strategies in acute lung injury.

PMID- 16977703
TI  - Fluid-management strategies in acute lung injury.

PMID- 16977704
TI  - Physical and performance differences among forwards, defensemen, and goalies in
      elite women's ice hockey.
AB  - Positional differences have been examined in women's basketball, field hockey,
      netball, and volleyball, but not in elite women's ice hockey. Our purpose was to
      describe and compare physical, fitness, and skating performance characteristics
      of forwards (F), defensemen (D), and goalies (G). Subjects were 112 University of
      Alberta women players (21.4 +/- 2.9 years of age). A full anthropometric battery
      was conducted on each player. Heath-Carter anthropometric somatotypes were
      calculated. Percent body fat (%fat) was estimated from both general and
      population-specific equations. Subjects performed off-ice fitness tests (vertical
      jump, 40-yd dash, Leger test for predicting .V(O2)max) and on-ice fitness
      (Modified 3-Repeat Sprint Skate Test-MRSS, blood lactate after sprint test) and
      skating performance tests (6.10-m acceleration test, Cornering S-Turn Agility
      Test). Descriptive statistics and multivariate analyses of variance were run
      using SPSS (Version 10.0) for the MacIntosh, with a significance level set a
      priori at p < 0.05. Significant positional differences were found for bicristal
      breadths (D > G, F > G); relaxed arm circumference (D > F, G > F); supraspinale
      and biceps skinfolds (G > D, G > F); and endomorphy (G > F). Significant
      differences among positions were also found for the MRSS (G > D > F) and agility
      tests (G > D, G > F). D tended to have the most robust build overall. F were
      leaner than D and G, and their smaller relaxed arm circumference measurements
      most likely reflect less subcutaneous fat on the upper arm. F had greater
      anaerobic power than D, followed by G, and they tended to have greater aerobic
      capacity. F and D were more agile than G. Performance demands appear to be
      position specific. F need to be the most versatile and fit because of a greater
      amount and variety of work performed both during practices and games; their
      required degrees of versatility and fitness are followed by those required of D
      and G.

PMID- 16977705
TI  - Thyroxine in goiter, H. pylori infection, and gastritis.

PMID- 16977706
TI  - Is cardiorespiratory fitness related to quality of life in survivors of breast
      cancer?
AB  - The purpose of this study was to investigate whether indices of cardiorespiratory
      fitness are related to quality of life (QOL) in women survivors of breast cancer.
      Using the European Organization for Research and Treatment of Cancer QLQ-30
      questionnaire, we assessed the QOL of 16 participants (age, 50 +/- 9 years; body
      mass, 66.6 +/- 9.6 kg). All participants performed incremental cycle ergometer
      exercise to determine several indices of cardiorespiratory fitness (e.g., peak
      oxygen uptake [.V(O2)peak, in L.min(-1), ml.kg(-1).min(-1)]), peak power output
      (PPO, in W), PPO/ body mass (W.kg(-1), peak heart rate (HRpeak, b.min(-1), peak
      ventilation (VEpeak), and .V(O2) and heart rate (HR) at the ventilatory (VT) and
      respiratory compensation (RCT) thresholds. Relationships between QOL and
      variables were assessed using Spearman rank-difference correlation tests. A
      significant inverse relationship (p < 0.05) was found for QOL scores and values
      for age (years) and body mass (kg) ( = -0.53), %HRpeak@VT ( = -0.59) and
      %VEpeak@VT ( = -0.61). A significant positive relationship (p < 0.05) was found
      for QOL and PPO/body mass ( = 0.59) and HRpeak ( = 0.78), .V(O2)@RCT (ml.kg(
      1.min(-1) ( = 0.51), power output (PO, expressed as either W or W.kg(-1) at RCT,
      and HR at RCT ( = 0.54). No other significant relationship was found between QOL
      and variables obtained from the tests. In conclusion, these findings highlight
      possible relationships between cardiorespiratory fitness and well-being in
      survivors of breast cancer. From a practical point of view, our data emphasize
      the need for this population to engage in programmed cardiorespiratory exercise
      training, mainly designed to improve VT and RCT. The improvement of both
      submaximal indices can have a beneficial effect on QOL.

PMID- 16977707
TI  - Chest X ray quiz. Position of endotracheal tube and near drowning.

PMID- 16977708
TI  - Classification of lumbopelvic pain disorders--why is it essential for management?

PMID- 16977709
TI  - Heart rate at lactate threshold and cycling time trials.
AB  - The purpose of this investigation was to relate the heart rate and lactate
      response during simulated cycling time trials to incremental laboratory tests.
      Subjects (N = 10) were tested for .V(O2)max (56.1 +/- 2.4 ml.kg(-1).min(-1) ) and
      lactate threshold during incremental tests to exhaustion. Power output and heart
      rate (HR) at threshold was assessed by 3 methods: lactate deflection point (LaT),
      onset of blood lactate accumulation (OBLA), and the point on the lactate curve at
      maximal distance from a line connecting starting and finishing power output
      (Dmax). Power output determined at these thresholds was 282.1 +/-4.2, 302.5 +/
      1.3, and 296.0 +/- 1.8 W, respectively, whereas HR was determined to be 88.6 +/-
      0.01, 92.2 +/- 0.01, and 91.0 +/- 0.01% of maximum, respectively. Power output
      and HR were significantly lower for LaT than for the other 2 methods (p < 0.05).
      On separate visits, cyclists were instructed to perform maximum efforts for 30
      and 60 minutes (30TT and 60TT). Lactate, HR, perceived exertion (RPE), and
      metabolic variables were measured during the time trials. During the 30TT,
      participants sustained a significantly higher lactate level (5.29 +/- 0.3 vs.
      3.43 +/- 0.3 mmol.L(-1), p < 0.001), percentage of maximum HR (%HRmax) (90.3 +/-
      0.02 vs. 84.6 +/- 0.01, p = 0.009), and overall RPE (15.5 +/- 0.5 vs. 14.4 +/-
      0.5, p = 0.009), than during the 60TT. .V(O2) was not significantly different
      between the time trials; however, .V(CO2) (p = 0.008), ventilation (p = 0.004),
      and respiratory exchange ratio (p = 0.02) were significantly higher during the
      30TT. Correlations were found between HR at LaT (r = 0.78), OBLA (r = 0.78), and
      Dmax (r = 0.71) for the 60TT, but not for the 30TT. These data suggest that
      despite a large variability in blood lactate during time trial efforts of 30 and
      60 minutes (from 1.8 to 10.8 mmol.L(-1)), HR was consistently 90% of maximum for
      the 30TT and 85% for the 60TT. HR during the 30TT was approximated by HR
      corresponding to OBLA and Dmax, whereas HR during 60TT was approximated by LaT.

PMID- 16977710
TI  - Perspectives on the recent decline in disability at older ages.
AB  - This brief summarizes a recent study exploring the decline in disability observed
      among the elderly population in national, longitudinal surveys between 1982 and
      1999. The brief outlines survey design features that may contribute to reports of
      declining disability. In addition, the brief explores social trends, such as
      reduced availability of informal care, increased use of assistive technologies
      and changes in respondents' perceptions of "disability" over time that may be
      important contributors to declining disability. Finally, the brief presents the
      results of a reanalysis of the National Long Term Care Survey (NLTCS) to evaluate
      the role of several survey design and social factors on reported declines in
      disability. Using alternative measures of disability, this reanalysis confirmed
      that disability declined among the elderly population. However, the study found a
      more gradual decline in any disability compared to previous analyses of the
      NLTCS. These results point to the importance of survey design features and
      societal trends in interpreting recent declines in disability among the
      elderly.Further, the effects of survey design and societal factors on disability
      estimates make it difficult to extrapolate current disability trends into the
      future and to predict costs to Medicare, Medicaid and other public programs that
      serve the elderly.

PMID- 16977711
TI  - Home health care quality conferences: promoting change through dialogue.
AB  - The following brief is based on the results of two conferences on home care
      quality hosted by the Center for Home Care Policy and Research of the Visiting
      Nurse Service of New York. For more information about the conference outcomes and
      proceedings please see: Feldman, P.H.,Peterson, L.E., Reische, L., Bruno, L., &
      Clark, A. (2004). Charting the course for home healthcare quality: Action steps
      for achieving sustainable improvement. Conference proceedings. Home Healthcare
      Nurse, 22(12): 841-850; and Feldman, P.H., Clark, A., & Bruno, L. (2006).
      Advancing the agenda for home healthcare quality: Conference proceedings and
      findings. Home Healthcare Nurse, 24(5): 282-290.

PMID- 16977713
TI  - Cases of Meralgia Paraesthetica.

PMID- 16977712
TI  - [A forehead mirror turned the wrong way more common than a stethoscope as an
      attribute of "motion picture physicians"].

PMID- 16977714
TI  - Field-flow fractionation of proteins, polysaccharides, synthetic polymers, and
      supramolecular assemblies.
AB  - This review summarizes developments and applications of flow and thermal field
      flow fractionation (FFF) in the areas of macromolecules and supramolecular
      assemblies. In the past 10 years, the use of these FFF techniques has extended
      beyond determining diffusion coefficients, hydrodynamic diameters, and molecular
      weights of standards. Complex samples as diverse as polysaccharides, prion
      particles, and block copolymers have been characterized and processes such as
      aggregation, stability, and infectivity have been monitored. The open channel
      design used in FFF makes it a gentle separation technique for high- and ultrahigh
      molecular weight macromolecules, aggregates, and self-assembled complexes.
      Coupling FFF with other techniques such as multiangle light scattering and MS
      provides additional invaluable information about conformation, branching, and
      identity.

PMID- 16977715
TI  - Physiological responses of skilled players during a competitive wheelchair tennis
      match.
AB  - The purpose of this study was to determine heart rate (HR, b.min(-1)) response
      during competitive match play of 6 men who were skilled wheelchair (WC) tennis
      players. Each participant completed an arm crank ergometer test that measured HR
      via a telemetry device and O2 via open circuit spirometry from rest until fatigue
      (.V(O2)peak). Each athlete participated in 2 competitive singles matches during
      which HRs were recorded in 5-second intervals and O2 was estimated using the
      corresponding HR values recorded during the arm ergometer tests. Data analysis
      revealed an average playing intensity of 69.4 +/- 8.9% of HRpeak and 49.9 +/
      14.5% of .V(O2)peak. In conclusion, it is recommended that skilled adult WC
      tennis players perform off-court aerobic conditioning as part of their training
      program, because the intensity of a competitive WC tennis match is sufficiently
      high enough to stress the cardiovascular system.

PMID- 16977716
TI  - Do we understand the emergent dynamics of grid cell activity?

PMID- 16977717
TI  - Role of energy systems in two intermittent field tests in women field hockey
      players.
AB  - The energetics of 2 field tests that reflect physical performance in intermittent
      sports (i.e., the Interval Shuttle Sprint Test [ISST] and the Interval Shuttle
      Run Test [ISRT]) were examined in 21 women field hockey players. The ISST
      required the players to perform 10 shuttle sprints starting every 20 seconds.
      During the ISRT, players alternately ran 20-m shuttles for 30 seconds and walked
      for 15 seconds with increasing speed. Anaerobic and aerobic power tests included
      Wingate cycle sprints and a .V(O2)max cycle test, respectively. Based on
      correlation and regression analyses, it was concluded that for the ISST,
      anaerobic energetic pathways contribute mainly to energy supply for peak sprint
      time, while aerobic energetic pathways also contribute to energy supply for total
      sprint time. Energy during the ISRT is supplied mainly by the aerobic energy
      system. Depending on the aspect of physical performance a coach wants to
      determine, the ISST or ISRT can be used.

PMID- 16977718
TI  - Outbreak news. Avian influenza, Indonesia--update.

PMID- 16977719
TI  - Outbreak news. Poliomyelitis, Ethiopia and Somalia.

PMID- 16977720
TI  - Assessment of maternal and neonatal tetanus elimination in Kerala state, India.

PMID- 16977721
TI  - [Regarding Miroslaw Zabka's article "Brain and spinal cord stimulation for
      treatment of movement disorders and pain syndromes--theoretical and practical
      guidelines", published in the Polish Journal of Neurology and Neurosurgery number
      1/2006].

PMID- 16977722
TI  - Growth and foliar nitrogen status of four plant species exposed to atmospheric
      ammonia.
AB  - A chamber study was conducted to evaluate the growth response and leaf nitrogen
      (N) status of four plant species exposed to continuous ammonia (NH3) for 12 weeks
      (wk). This was intended to evaluate appropriate plant species that could be used
      to trap discharged NH3 from the exhaust fans in poultry feeding operations before
      moving off-site. Two hundred and forty bare-root plants of four species
      (Juniperus virginiana (red cedar), Gleditsia triacanthos var. inermis (thornless
      honey locust), Populus sp. (hybrid poplar), and Phalaris arundinacea (reed canary
      grass) were transplanted into 4- or 8-L polyethylene pots and grown in four
      environmentally controlled chambers. Plants placed in two of the four chambers
      received continuous exposure to anhydrous NH3 at 4 to 5 ppm while plants in
      another two chambers received no NH3. In each of the four chambers, 2 to 4 plants
      per species received no fertilizer while the rest of the plants were fertilized
      with a 100 ppm solution containing 21% N, 7% phosphorus, and 7% potassium. The
      results showed that honey locust was the fastest-growing species. The superior
      growth of honey locust among all species was also supported by its total biomass,
      root, and root dry matter (DM) weights. For all species there was a trend for
      plants exposed to NH3 to have greater leaf DM than their non-exposed counterparts
      at 6 (43.0 vs. 30.8%; P = 0.09) and 12 wk (47.9 vs. 36.6%; P = 0.07), and
      significantly greater (P <or=0.05) leaf N content at 6 (6.44 vs. 3.67%) and 12 wk
      (7.05 vs. 3.51%) when exposed to NH3. Numerically greater leaf DM due to NH3
      exposure was also consistently measured in poplar at both sampling periods.
      Hybrid poplar, as well as honey locust and reed canary grass, deposited 1.5 to 2
      fold greater N in their leaves than red cedar tissues as a result of NH3 exposure
      compared to non-exposed plants. Regardless of the effect of NH3 on foliar color
      and damage score of the plants, the increase of foliar N content (g 100 g-1 of
      fresh foliage weight) after NH3 exposure at 6 and 12 wk was 0.45 and 0.87 for
      grass,1.25 and 1.34 for locust, and 2.67 and 6.09 for poplar. However, only honey
      locust likely benefited from ambient NH3 as indicated by its consistent leaf
      color quality and lower damage score, compared with other species that were
      adversely affected by atmospheric NH3.

PMID- 16977723
TI  - [A 74-year-old unconscious woman with myoclonia and seizures].

PMID- 16977724
TI  - [Intoxication with psychopharmaceuticals].

PMID- 16977725
TI  - Bibliography. Current world literature. Endoscopy.

PMID- 16977726
TI  - Marketing. The power of TV.

PMID- 16977727
TI  - Tobacco control--mixing health and advocacy.

PMID- 16977728
TI  - Conflict puts pressure on cancer-care resources in Lebanon.

PMID- 16977729
TI  - Study supports 20-year interval for colonoscopy screening.

PMID- 16977730
TI  - New prediction model for melanoma.

PMID- 16977731
TI  - Postmenopausal hormone therapy increases breast-cancer risk.

PMID- 16977732
TI  - Exercise could improve colorectal-cancer survival.

PMID- 16977733
TI  - New consumer guidance on herbal medicines.

PMID- 16977734
TI  - IOM report recommends comprehensive strategies to reduce medication errors.

PMID- 16977735
TI  - The conduct of socially sensitive research: sex offenders as participants.
AB  - This article examines some extra-research variables inherent in conducting
      community-based research with child molesters and other sex offenders. These
      include such issues as informed consent with court-referred participants,
      confidentiality when interagency collaboration is necessary, and duty to take
      proper care. Methods for establishing the scientific credibility of the project,
      responding to client grievances, dealing with client crises, and protecting staff
      and the surrounding community also are addressed. Adopting procedures similar to
      those described here could be an important step in ensuring the viability of
      other socially sensitive research projects.

PMID- 16977736
TI  - Ethical issues in field research: balancing competing values.
AB  - An ethical issue becomes a dilemma when the psychologist is pulled in different
      directions by competing values. This paper will focus on the conflict between
      experimental and ethical values inherent in field research. The problem has
      special significance in community psychology, which gives priority to studying,
      in natural settings, those affected by social problems. An example is given of
      research that required observation of family interaction in the homes of
      convicted child abusers. The case demonstrates that the value of ecological
      validity often conflicts with the need to protect privacy and obtain uncoerced
      consent. Other ethical constraints, including the duty to report lawbreaking and
      to protect the public from harm, may threaten research validity.

PMID- 16977737
TI  - The potential right of chronically ill adolescents to refuse life-saving medical
      treatment--fatal misuse of mature minor doctrine.

PMID- 16977738
TI  - The retreat from Gillick.

PMID- 16977739
TI  - Rimonabant: new drug. Obesity: loss of a few kilos, many questions.
AB  - (1) The treatment of obesity is based on calorie reduction and moderate physical
      activity. (2) Rimonabant, a CB1 cannabinoid receptor antagonist, is marketed in
      Europe for the adjuvant treatment of obesity, in combination with a low-calorie
      diet and physical exercise. (3) Four double-blind placebo-controlled trials
      involving about 6500 patients show that, when combined with a low-calorie diet,
      rimonabant 20 mg/day leads to an average weight loss of 4 or 5 kg more than
      placebo after one year of treatment. This is similar to the weight loss reported
      with orlistat (indirect comparison). Effects on the lipid profile are similar to
      those reported with sibutramine. (4) Rimonabant has not been shown to reduce
      morbidity or mortality. Patients regain the weight they lost within about 9
      months after rimonabant withdrawal. (5) Three placebo-controlled trials have
      evaluated rimonabant in smoking cessation. The available results (a single
      conference abstract) are inconclusive. In early 2006 the FDA and the European
      Medicines Agency refused to approve rimonabant for this use. (6) Adverse effects
      mentioned in published clinical trials of rimonabant include mental disorders
      (anxiety, depression), neurological disorders (dizziness) and gastrointestinal
      disorders (nausea, diarrhoea). No postmarketing safety data are available. The
      possible long-term adverse effects of rimonabant are unknown. (7) In practice,
      when drug therapy is considered for weight loss, it seems unwise to prescribe
      rimonabant: this new drug has only limited symptomatic effects and its adverse
      effects, especially in the long term, are poorly documented.

PMID- 16977740
TI  - Bibliography. Current world literature. Sarcomas.

PMID- 16977741
TI  - Bibliography. Current world literature. Gastrointestinal tract.

PMID- 16977742
TI  - John Homans' impact on diseases of the veins of the lower extremity, with special
      reference to deep thrombophlebitis and the post-thrombotic syndrome with
      ulceration.

PMID- 16977743
TI  - Three years' experience with computer-based intensive care of patients following
      open heart and major vascular surgery.
AB  - The authors present their experiences with the Roche-5000 Computer-Based
      Intensive Care System in the management of 100 consecutive patients who have
      undergone open heart or major vascular surgery. The system performs the following
      junctions: (1) numerical and graphic display, out-of-limits alarms, storage and
      printout of 12 biological and surgical parameters, including chest drainage and
      urine output, by on-line direct monitoring; (2) display, storage, and printout of
      all additional laboratory and clinical data by manual input; (3) automatic demand
      regulated transfusion and infusion program; (4) a program of medical logic, which
      includes situation analysis based on the above, two way dialogue with the
      computer, treatment recommendations to the physician, selective nursing and
      laboratory orders, acid-base analysis, and instructions for respirator setting.
      It was found that the computer-monitored patients recovered faster and smoother,
      with fewer fluctuations in the measured parameters and fewer postoperative
      complications than did those treated by conventional methods. One additional
      important effect of the system was that the nurse, relieved of the mechanical
      tasks of measuring, charting, and recording, was left with a greater amount of
      time for the care of the patient's personal needs. It seems ironic that such a
      technical advancement in electronics not only made the recovery faster and safer
      but also created a more humanistic approach in patient care, through better
      application of basic nursing techniques.

PMID- 16977744
TI  - Geometric comparison of aortic bifurcation prostheses to the normal and
      atherosclerotic human aorta, and clinical trial of a vertical seamed bifurcation
      prosthesis.
AB  - The 12 bifurcation prostheses generally available in the United States were
      compared. One was woven Teflon, two woven Dacron, and nine knitted Dacron. Ten
      were "seamless" in construction, and two were "seamed," but close examination
      revealed that all prostheses actually were seamed at the bifurication point. The
      grafts varied considerably in construction, porosity, and geometry. To compare
      the geometries, each prosthesis was preclotted in plasma, inflated to 120 mm. Hg,
      and quick frozen in alcohol and dry ice. Transverse and frontal bisections of the
      frozen specimens were photographed with a millimeter scale for sizing. For
      comparison, eight human aortofemoral bifurcations were distended and frozen
      similarly. The prostheses had far wider bifurcation shelves than did the normal
      aortas. The five normal human aortofemoral bifurcations had an average ratio of
      limb: body diameter of 0.61; the three atherosclerotic specimens averaged 0.49.
      The prostheses had an average limb:body diameter ratio of 0.48. or the "seamless"
      grafts, 0.48 for the circular transverse limb-seamed grafts, and 0.58 for the
      vertical-seamed grafts. Vertical-seamed aortic bifurcation grafts implanted in
      102 patients between 1970 and 1976 (average follow-up, 29.5 months) have
      developed only a single limb closure, at 53 months.

PMID- 16977745
TI  - A comparison of the late patency rates of axillobilateral femoral and
      axillounilateral femoral grafts.
AB  - A total of 130 axillofemoral grafts were peformed in 120 patients from 1966 to
      present; 66 were axillobilateral femoral moral and 64 were axillounilateral
      femoral grafts. The average patient age was 66 years. The indications for
      operation were occlusive disease with rest pain or gangrene in 102 patients,
      severe claudication four, and bypass of a thoracic aneurysm in one. The one month
      operative mortality rate was 8 percent (ten patients). Four deaths occurred in
      elderly patients operated upon as emergencies with acute aortic occlusion. In the
      126 elective cases, there were six postoperative deaths (4.7 percent). Twenty
      thrombectomies were performed in 15 axillobilateral femoral grafts of which 15
      (75 percent) were successful. In the unilateral grafts there were 25
      thrombectomies in 22 grafts, of which only eight (32 percent) were successful.
      The 5 year patency rate by the life-table method was 74 percent for
      axillobilateral femoral grafts and 37 percent for axillounilateral femoral
      grafts. This difference in patency rates is statistically significant (p < 0.01).
      Average flow measured by electromagnetic flow meter in six axillobilateral
      femoral grafts was 621 c.c. per minute and in 11 unilateral femoral grafts was
      273 c.c. per minute. We attribute the higher patency rate in axillobilateral
      femoral grafts to this increased flow. These data indicate that axillobilateral
      femoral grafts may be performed with anticipation of a 5 year patency rate
      comparable to that with conventional aortoiliac reconstruction and that
      axillobilateral femoral grafts should be performed in preference to
      axillounilateral femoral grafts in poor-risk patients requiring extra-anatomic
      bypass for aortoiliac occlusive disease.

PMID- 16977746
TI  - "Redo" surgery after operations for aneurysm and occlusion of the abdominal
      aorta.
AB  - During a 20 year period, 1,287 patients were submitted to arterial reconstruction
      for aneurysm and occlusion of the aorta and iliac arteries. Good results were
      obtained in 1,230 (95.6 percent). Of these, 83 (6.4 percent) returned for
      reoperation. Reoperation was performed also in 18 patients operated upon
      elsewhere. Thus this series of cases of reoperation consists of 101 patients. The
      most common cause for reoperation and interval after initial procedure were
      recurrent obstruction--44 to 90 months, false aneurysm--94 months, and infection-
      25 months. The most common complication in patients treated initially for
      aneurysm was false aneurysm and recurrent obstruction in the patients treated for
      aortoiliac artery occlusion. Infection was rare and occurred in both groups.
      False aneurysm was due to fragmentation of suture in most cases and recurrent
      obstruction was related to progression of the disease, the type of original
      procedure employed, and technical factors. Although various methods of treatment
      were employed, the preferred are (1) aneurysm replacement for false aneurysm, (2)
      bilateral aortofemoral or aortapopliteal bypass for recurrent obstruction with
      profundaplasty when necessary, and (3) bilateral axillofemoral or axillopopliteal
      bypass and graft removal for infection. The results of reoperation were
      considered to be satifactory with survival in 89 (88 percent) and good functional
      results in 84 (94 percent) of survivors. Amputation was necessary in only five (6
      percent) patients.

PMID- 16977747
TI  - Bilateral renal artery stenosis and renovascular hypertension.
AB  - Experience with the diagnostic evaluation and operative management of 38
      hypertensive patients having bilateral renal revascularization is presented.
      Twenty-four patients had atherosclerotic occlusions and 14 had fibromuscular
      dysplasia. Renal vein renin assays (RVRA) and/or split renal function studies
      (SRFS) were performed in 37 of the 38 patients before operation. Although RVRA
      was negative in 29 percent and SRFS negative in 31 percent, 24 of 26 patients (92
      percent) having both tests done had at least one positive study. Twenty-one
      patients had simultaneous bilateral repairs and 12 had staged bilateral
      reconstructions. The incidence of technical failures in these two groups was 21
      and 9 percent, respectively. Excluding three uncorrected technical failures and
      two patients with recurrent branch renal artery lesions, 90 percent of patients
      with atherosclerosis and all patients with fibromuscular dysplasia had a
      favorable blood pressure response to operation. This study supports the use of
      both RVRA and SRFS in the diagnostic evaluation of hypertensive patients with
      renal artery stenosis. If these functional tests lateralize to one side, repair
      of that side only is recommended. If the functional studies do not lateralize,
      operation is suggested only when hypertension is severe and is not controlled
      readily with medications. In this circumstance reconstruction of the side that
      appears to be diseased most severely is recommended. Contralateral repair is
      undertaken only when hypertension persists and when repeat functional studies
      lateralize to the unoperated side.

PMID- 16977748
TI  - Lessons we have learned from the transplant experience.

PMID- 16977749
TI  - Progress in legal definition of brain death and consent to remove cadaver organs.
AB  - The availability of cadaver kidneys for transplantation falls far short of the
      needs of a rapidly expanding population of patients on chronic hemodialysis.
      Kidneys with the least ischemic injury come from donors with fatal head injury or
      stroke; such kidneys can be removed from a "beating-heart" cadaver after
      declaring death on the basis of brain death. To clarify the legal status of brain
      death and to encourage salvage of transplantable kidneys with minimal ischemic
      injury, 12 states already have codified the concept of brain death. Although the
      first few laws were lengthy and included medical terms, six of the last seven
      laws have used one or two models proposed by the American Bar Association (ABA)
      and the Institute of Society, Ethics and Life Sciences, Hastings-on-Hudson, N. Y.
      The ABA proposal is the simpler of the two models and should provide the basis
      for future state laws. In addition, the National Conference of Commissioners on
      Uniform State Laws plans to present a model law to define death and the
      liabilities of a physician who declares death on the basis of brain death by mid
      1977. While state legislatures have written laws that establish the legality of
      the concept of brain death, medical groups have sought to define the medical
      criteria for its determination. The most recent list of criteria comes from a
      National Institutes of Health-supported Collaborative Study on Cerebral Survival,
      as follows: (1) unresponsivity, (2) apnea, (3) dilated pupils and absent cephalic
      reflexes, (4) electrocerebral silence, (5) a confirmatory test of absent cerebral
      blood flow (angiography, isotope bolus curve, retinoscopy, or
      echoencephalography).

PMID- 16977750
TI  - Prolonged survival of xenografts after organ culture.
AB  - Recent reports demonstrate that culture of thyroid allografts before
      transplantation results in prolonged and sometimes indefinite survival. The loss
      of passenger leukocytes during organ culture was discussed as a possible reason
      for these findings. Recent data from a genetically defined system in the mouse
      demonstrated that passenger leukocytes play an important role in providing a
      helper stimulus which potentiates the generation of cytotoxic T cells to
      serologically defined determinants. To ascertain whether this mechanism also is
      involved in a xenogeneic system, cultured Wistar thyroids were transplanted to
      DBA/2 mice. The experimental system used was described first by Lafferty and co
      workers. Thyroid function was determined by 125-iodine uptake of the graft and by
      histology. Fresh Wistar thyroids were rejected after a short period of good
      function on the sixth day after transplantation. Culturing for 10 days resulted
      in a prolonged graft function up to the fifteenth day. However, if the thyroids
      were kept in culture for 27 days, no functional signs of rejection could be
      detected on the twenty-fifth day after transplantation by iodine uptake. The
      iodine uptake ratio was 47.1 (control group on day 6 was 2.4). Injection of 10(5)
      fresh donor cells at the time of transplantation reversed the effect of long-term
      organ culture.

PMID- 16977751
TI  - The effect of vagotomy on the canine enterogastrone mechanism.
AB  - The effect of truncal vagotomy on the enterogastrone mechanism was evaluated in
      dogs with Heidenhain pouches and gastric and pancreatic fistulas. During
      continuous infusion of pentagastrin, 8 microg-Kg.-hr., HCl was infused into the
      duodenum in doses of 12, 18, and 24 mEq. per hour before and one month following
      transthoracic vagotomy. The effect of vagotomy on the inhibition of pentagastrin
      stimulated Heidenhain pouch hydrogen ion output produced by the endogenous
      release of duodenal hormones was evaluated. The results indicate that there was
      no difference in the degree of inhibition produced by 12 and 18 mEq.
      intraduodenal HCl before and after vagotomy. When 24 mEq. per hour HCl was
      infused, the percent inhibition was significantly greater after vagotomy compared
      to values before vagotomy. The D50 of intraduodenal acid for inhibition of
      Heidenhain pouch hydrogen ion output was not altered by vagotomy, whereas the
      calculated maximal response (inhibition) was increased after vagotomy. Pancreatic
      volume was greater after vagotomy when compared to values before vagotomy, when
      24 mEq. of HCl per hour was infused into the duodenum. These data suggest that
      vagotomy does not impair the effectiveness of the enterogastrone mechanism and at
      high doses of intraduodenal acid may augment it.

PMID- 16977752
TI  - The successful transplantation of frozen parathyroid tissue in man.
AB  - Autologous parathyroid tissue frozen in liquid nitrogen for 6 weeks was
      transplanted successfully into the forearm muscle of an aparathyroid, uremic
      patient with renal osteodystrophy. Two years later the parathyroid graft was
      biopsied. Histologic evaluation revealed normal architecture, and there was
      ultrastructural demonstration of secretory granules within parathyroid cells.
      Physiologic function of the patient's graft was documented by the presence of a
      normal serum calcium concentration in the absence of replacement therapy and by a
      high level of parathyroid hormone in the venous blood draining the grafted muscle
      bed.

PMID- 16977753
TI  - Unilateral hepatic duct obstruction in the primate.
AB  - The effects of obstruction of one hepatic duct were investigated in two studies
      in the rhesus monkey. A model to divide bile flow from the two sides of the liver
      was developed in the first study. Bile flow from one side of the liver was
      obstructed and backflow from the obstructed biliary tract was investigated in
      five animals. Test solutions containing sulfobromophthalein (BSP) and conjugated
      cholic acid-14C were introduced into the obstructed side of the liver at
      pressures below and above the maximum secretory pressure. These solutes were
      detected in the circulation and in the bile on the free side of the liver. BSP,
      secreted on the free side, was conjugated normally (52.7 percent) for this
      species. There was also backflow of water from the obstructed side and continuing
      secretion into the obstructed side. It was determined that there were no
      functionally significant biliary communications between the two separately
      cannulated portions of the liver. In the second study, graded unilateral
      obstruction and recovery were studied in five animals. Bile flow, eyythritol-14C
      clearance, and bile acid, bilirubin, and bicarbonate secretion rates were reduced
      during obstruction and recovery. The bile:plasma ratio of erythritol-14C fell
      significantly (1.13 to 0.97) and the bicarbonate concentration increased during
      partial obstruction. On the free side, bile flow, erythritol-14C clearance, and
      bile acid secretion rates increased during obstruction. The increase in bile flow
      was due largely to an increase in canalicular bile acid-dependent flow. The
      studies indicated that reduced bile flow during acute obstruction is due to both
      hydrostatic backflow and secretory failure. The latter occurs mainly at the
      canalicular level, whereas the bile ductules are spared at least relatively.
      During acute obstructions compensations in unobstructed portions of the liver are
      due to increased secretion of solute at the canaliculus.

PMID- 16977754
TI  - A comparison of autografts and frozen, irradiated homografts in canine femoral
      venous reconstruction.
AB  - Autogenous veins are the ideal substitute for bridging venous defects.
      Experimentally, fresh homografts have patency rates comparable to autografts.
      However, a method of preservation must be employed if homografts become practical
      for clinical use. In this study, homografts were frozen, irradiated, and stored
      for a total of 6 weeks. Following femoral venous reconstruction, patency rates
      between frozen, irradiated homografts and fresh autografts were compared and
      found to be similar over a 6 month period. Recanalization of the frozen,
      irradiated homografts occurred at the same rate as did that of the autografts.
      This study concludes that cryopreservation and irradiation are suitable methods
      of preservation that do not adversely affect patency. In addition irradiation
      will sterilize tissue and may decrease the potential of the graft to stimulate
      the recipient's immunologic system.

PMID- 16977755
TI  - Fibromuscular dysplasia of the internal carotid arteries.
AB  - Seven patients with fibromuscular dysplasia of the internal carotid arteries have
      been operated upon at Walter Reed Army Medical Center. One lesion was treated by
      graduated dilatation with Bake's dilators combined with resection, end-to-end
      anastomosis, and vein patching of a tortuous segment. All other lesions were
      treated by graduated dilatation with an arterial dilator-shunt. All of these
      patients are asymptomatic presently. One patient has been operated upon recently
      because of symptoms related to the previously unoperated side as well as mild
      symptoms related to the previous operation. Two other patients with
      arteriographic evidence of fibromuscular dysplasia are being followed clinically.
      One is asymptomatic and one has minimal symptoms. Both are being treated with
      acetylsalicylic acid in hopes of preventing microembolization from these lesions.
      Important technical considerations in treating this condition are meticulous
      dissection of the internal carotid artery as near to the base of the skull as
      possible, confining the arteriotomy to the region of the carotid bulb, and
      straightening the carotid artery while passing the dilator under direct vision. A
      technique for routine shunting in these patients now is available.

PMID- 16977756
TI  - Aspergillus-induced small bowel obstruction in a leukemic newborn.
AB  - An infant with congenital acute myelocytic leukemia, who was being treated with
      chemotherapeutic agents, developed obstruction and infarction of the ileum due to
      occlusion of mesenteric arteries by Aspergillus hyphae. This case demonstrates
      how blood vessel occlusion by occult aspergillosis can present clinically as a
      surgical emergency.

PMID- 16977757
TI  - The fate of National Institutes of Health applications from departments of
      surgery.

PMID- 16977758
TI  - DVT or not DVT?

PMID- 16977759
TI  - DVT or not DVT?

PMID- 16977760
TI  - DVT or not DVT?

PMID- 16977761
TI  - [Tobacco publicity in Spain].

PMID- 16977762
TI  - [The ethics of clinical trials in primary care].

PMID- 16977763
TI  - [Factors which affect the completion of the static register in primary care
      clinical notes].
AB  - OBJECTIVE: We set out to analyse factors which might affect the completion of the
      "static" register in the Primary Care clinical notes. DESIGN: Crossover and
      observation study with a control of the confusion in data analysis. SETTING:
      Albaycin Health Centre (Granada). PATIENTS AND OTHER PARTICIPANTS: A random
      sample of 428 sets of Primary Care clinical notes. MEASUREMENTS AND MAIN RESULTS:
      The "static" register showed over 50% observance in the sections on case history,
      allergies, tobacco and alcohol; whereas in housing (42%) and diet and physical
      activity (25%), the observance diminished until reaching its lowest level in
      counter-indicated medicines, anti-tetanus vaccination, a vaccine biography and
      family notes (< 10%). Age and gender variables showed virtually no association
      with the completion of the register. The static register was significantly better
      for husbands/wives as against children, for patients included in health
      programmes, for those included in adult rather than other types of programme, for
      those with smaller-sized families, for patients who used the Centre more and also
      for three of the doctors as against a fourth. Finally we constructed an overall
      indicator of the static register (OISR) which was submitted to a process of
      internal validation and was object of a multiple linear regression model which
      explained 51.3% of the variability. CONCLUSIONS: We underline the need to go
      deeper into those factors affecting the register as a first step towards
      understanding its completion. In this way we will find criteria for improving it
      or modifying the organisation of its observance and/or format. We discussed a
      method of overall indicators for tackling such a problematic.

PMID- 16977764
TI  - [Communication between primary care and specialists].
AB  - OBJECTIVE: To assess how well referral and referral-back documents for
      rheumatology patients going back and forth between a health area's Primary Care
      and the specialist clinics are filled in. DESIGN: A descriptive retrospective
      study. Sevilla Central Health area. PATIENTS: These were the 233 patients with a
      referral document in their Clinical Notes, who were sent from Primary Care (both
      Health Centres (HC) and out-patient clinics (OC)) to the Rheumatology Service
      during 1991 (233 cases). MEASUREMENTS AND MAIN RESULTS: Out of the total, 69.96%
      (163) came from General Practitioners in out-patient clinics and 30.04% (70) from
      HC Family or General doctors. In HC the referral document was completed better
      than in OC, in the areas of clinical history, physical investigation and
      laboratory data. How well the referral-back document was filled in was
      independent of where the patient was referred from. 30.67% of the OC referrals
      and 15.71% of the HC ones were suggested by Area Specialists, without any
      significant differences existing. CONCLUSIONS: Patients coming from HC have their
      referral document better completed than those referred from out-patient clinics.
      The return document the HC patients take back is no better filled in by the
      rheumatologists. A high percentage of rheumatology referrals are suggested by
      Area Specialists but processed through Primary Care.

PMID- 16977765
TI  - [Indicators of follow-up activities undertaken by an arterial hypertension unit
      over a 5 year period].
AB  - OBJECTIVE: To assess the efficacy and effectiveness of an AHT programme by means
      of indicators which analyse the coverage, results and attendance. SETTING: AHT
      unit at the Health Centre in Novelda, Alicante. DESIGN: A quasi-experimental
      design of internal comparison with temporal series. The years analysed were 1985,
      '87, '88 and '90. The following were assessed: support, therapeutic compliance,
      risk level, weight, monitoring, visits per year, therapy, risk factors. PATIENTS:
      A cohort of 266 hypertense patients (175 women and 91 men). MEASUREMENTS AND MAIN
      RESULTS: The Unit significantly increased the number of patients being monitored
      and treated (WHO 46.7% and JNC 9.1%), but never exceeded 60%. Serious risk was
      eliminated and moderate risk went down (27.7%). Visits to the Centre were reduced
      by 2.8 per year. Of risk factors, weight did not go down, but
      hypercholesterolaemia diminished by 48.4%, hypertriglyceridaemia by 9.8%,
      hyperglycaemia by 4.4%, hyperuricaemia by 7.9% and tobacco addiction by 19.9%.
      CONCLUSIONS: These figures contain extremely interesting information. They reveal
      the achievements and difficulties of clinical practice and point to practical
      strategies.

PMID- 16977766
TI  - [Analysis for different age groups of the coverage of the preventive measures and
      health publicity programme].
AB  - OBJECTIVE: To find out whether the preventive measures proposed in the Preventive
      Measures and Health Promotion Programme (PMHPP) are a priority among youth with a
      low level of health service demand. DESIGN: Descriptive, retrospective study.
      SETTING: Primary Care Centre. PATIENTS: 378 patients (179 men and 199 women)
      making up a representative sample stratified by age and gender. MEASUREMENTS AND
      MAIN RESULTS: The particular page for recording PMHPP was found in only 13% of
      the medical records of the 15-24 age group (28.32% of the total sample). Tobacco
      and alcohol habits were tackled at the recommended intervals significantly less
      (p < 0.001) in people under 25 than in those over. Only 20% of the patients
      between 15 and 25 had both their weight and height recorded (39.1% in total). The
      7-14 year-old group had an almost 60% correct immunisation against tetanus as
      against 24.56% for the rest (p < 0.001). In 66% of the records of women under 35
      their immunity status against German Measles was not recorded. CONCLUSIONS: The
      PMHPP reaches least those who would most benefit from a preventive approach to
      problems such as tobacco, alcohol and overweight. We must focus our efforts on
      changing this situation: if not, the programme's effectiveness will continue to
      be limited.

PMID- 16977767
TI  - [Study on the accuracy of three portable reflectometers to determine glycaemia
      levels: Reflolux II, Glucometer II and Glucoscot II].
AB  - OBJECTIVE: To evaluate the accuracy of three portable glucoreflectometers
      (Reflolux II, Glucometer II and Glucoscot II), comparing them with the laboratory
      (Hitachi 704, exokinase method) and checking their reliability when measurements
      were repeated. DESIGN: A validity and reliability study. Three methods were
      evaluated and another used as reference. SETTING: The study was carried out at an
      urban Health Centre in Albacete. PATIENTS AND OTHER PARTICIPANTS: A sample
      composed of 102 types I and II diabetic patients included in an adult programme
      was used. The choice was made on the basis of a simple randomized sampling of the
      centre's records with no exclusion criteria. MEASUREMENTS AND MAIN RESULTS: The
      following correlations were obtained: Reflolux II = 0.94, Glucometer II = 0.85,
      Glucoscot II = 0.85. The difference of averages between machines and laboratory,
      using venous blood was: Reflolux II (2.5 +/- 2.9; t = -1.67: p > 0.01),
      Glucometer II (40.2 +/- 4.8; t = -16.42: p < 0.001), Glucoscot II (32.8 +/- 4.7:
      p < 0.001). Variation coefficients (n = 30): Reflolux II (8.1%); Glucometer II
      (8.5%); Glucoscot II (3.6%). CONCLUSIONS: Reflolux II was shown to be a more
      accurate machine than the other two under study. It is therefore the most
      suitable for use in Primary Care.

PMID- 16977768
TI  - [The adaptation for a health centre of a functional screening process aimed at
      elderly people].
AB  - OBJECTIVE: To find out what the functional capacity of people aged 75 or over is
      and to adapt the screening questionnaire for further use. DESIGN: Descriptive
      crossover study. SETTING: Health Centre. PATIENTS AND OTHER PARTICIPANTS: People
      aged 75 or over registered at the Health Centre (HC). 78 people were chosen by
      systematic sampling. There were 18 losses. MEASUREMENTS AND MAIN RESULTS: A
      screening questionnaire was administered to make a clinical, functional and
      social assessment and record problems and performances. The average time taken
      per questionnaire was 28 minutes (SD 6.9). 76.7% completed it at the HC. There
      was a notably high percentage of problems detected (21.8%): 209 out of the 960
      possible boxes for problems. Over 40% of these problems--with the exception of
      boxes for economic status and mobility--had previously either not been identified
      or were not treated. Hearing, sight and teeth were the most frequent complaints
      (33.3%, 51.6% and 51.6%, respectively) and were unidentified or untreated in 85%,
      67.7% and 80.6% of cases. CONCLUSIONS: We consider that the systematic
      installation of this adapted screening method would be useful.

PMID- 16977769
TI  - [Nutrition in pregnant women: a study of dietary habits in two base health
      areas].
AB  - OBJECTIVE: To analyse the dietary habits of pregnant women in two base Health
      areas and to propose modifications in any damaging patterns found. DESIGN: A
      descriptive study of a crossover type using weekly dietary questionnaires on food
      consumption and a 24-hour record. SETTING: Almanjayar and Cartuja Health Centres
      in Granada. PARTICIPANTS: Pregnant women being monitored at the Health Centres
      who were chosen by randomized sampling (N = 52). MEASUREMENTS AND MAIN RESULTS:
      We studied the following variables: total energy consumption; intake of
      carbohydrates, lipides, proteins, fibre, Ca, Mg, Zn, Fe and hydrosoluble and
      liposoluble vitamins. Average energy consumption was 2516 Kcal per day, although
      14.46% of the pregnant women consumed less than 2200 Kcal and in 9.6% average
      consumption was below 1800 Kcal per day. The energy percentages of total
      consumption are excessive in the case of proteins (21%), lightly increased in
      Carbohydrates (51.8%) and acceptable in Lipides (27.2%). In the following there
      were notable intake deficiencies: Ca (69%), Fe (38.4%), Mg (53.8%), Vit D
      (49.7%), Folic Acid (81%) and Fibre (33%). On the question of how often food was
      consumed, we should note the scant consumption of vegetables and alcohol and
      excessive consumption of refined Carbohydrates. CONCLUSIONS: There are no big
      nutritional imbalances. The following are necessary: to maintain energy intake
      between 2200 and 2600 Kcal per day; to find a new equilibrium between animal and
      vegetable protein consumption, to diminish the intake of complex and refined
      Carbohydrates and to increase the intake of Fe, Ca, Folic acid and Vitamin D.

PMID- 16977770
TI  - [An approach to nutritional support at the primary care level for HIV-infected
      patients].

PMID- 16977771
TI  - [Primary care in Europe].

PMID- 16977772
TI  - [Diagnosis of the somatisation disorder: usefulness of a mnemonic system].

PMID- 16977773
TI  - [Concerning two cases of dysaesthesia in the chin].

PMID- 16977774
TI  - [Interpretation of the Toxoplasma gondii serology in pregnancy].

PMID- 16977775
TI  - [The tobacco habit in people over 65].

PMID- 16977776
TI  - [The classification, diagnosis, control and treatment of asthma].

PMID- 16977777
TI  - [Molecular biology background of inflammatory bowel disease].
AB  - The exact pathological background of inflammatory bowel disease has not been
      clarified yet. Many aspects of genetical and environmental factors, as well as
      certain alterations of the functions of epithelial cells and immunoregulation
      which may attenuate chronic inflammation in the gastrointestinal tract are known.
      These three components have many connecting points. Among the inflammatory bowel
      disease genes we know only the function of the NOD2/CARD gene, and we have some
      idea about the OCTN and DRG genes. The function of the intestinal epithelial
      cells is changed in inflammatory bowel disease. The latter two genes may have a
      role in the increased permeability, so as the tumor necrosis factor alpha,
      interferon gamma may play affect it. The interleukin-10 helps the mucosal
      integrity. The interleukin-6 production is elevated in these diseases, and the
      interleukin-8 level can be elevated in case of mutation of toll like receptor 5.
      The tumor necrosis factor alpha, interferon gamma and lymphotoxin-3-alpha
      increased the chemokine secretion and adhesion molecule expression also. The
      amount of certain cytokines are changed in inflammatory bowel disease. There were
      no association between the incidence and phenotype of Crohn's disease and
      cytokine gene polymorphisms, except the interleukin 6 gene. It seems that these
      alterations are secondary, and don't play a major role in the pathogenesis of
      inflammatory bowel disease.

PMID- 16977778
TI  - [Experience with gemcitabine-carboplatin chemotherapy in relapsed ovarian
      cancer].
AB  - Despite the progress that has been achieved in the primary therapy of ovarian
      cancer, unfortunately, the disease relapses resulting death in a lot of patients.
      This is the rationale for several new chemotherapy trials, however the expected
      results are awaited yet. The pyrimidine analogue drug gemcitabine belongs also to
      this group of hopeful therapies to increase the outcomes. PATIENTS AND METHODS:
      22 patients with platinum-resistant, recurrent epithelial ovarian carcinoma, were
      treated with gemcitabine, in 98 courses in the Gynecologic Department at National
      Institute of Oncology, Budapest. Gemcitabine was applied in combination
      chemotherapy with carboplatin in the 2-8th line with the gemcitabine dose of 1000
      mg/qm/d 1, 8 and carboplatin dose of AUC 4/d 1, in 3 week courses. Progression
      free interval was calculated by GraphPad Prism (version 2.0) program. RESULTS: A
      39% overall response and a median 3 months progression free interval were
      resulted. Complete response was found only in one patient. CONCLUSION:
      Combination therapy with gemcitabine and carboplatin showed only limited
      responses in the authors' relapsed ovarian cancer patients. It seems to authors
      the lesser progression free interval is resulted by the resistant clones of the
      tumour due to the several (median 4) unsuccessful previous chemotherapies. The
      authors' early experience with gemcitabine underlines the good tolerability and
      the possibility of outpatient administration of the drug as well.

PMID- 16977779
TI  - [Use of biochemical markers to predict the outcome of pregnancies conceived by in
      vitro fertilization].
AB  - BACKGROUND: Pregnancies obtained after in vitro fertilization and embryo transfer
      are at increased risk for an adverse outcome compared with women who conceive
      naturally. Multiple gestations also occur more frequently after in vitro
      fertilization. Therefore, there is a need for markers that accurately detect the
      establishment of pregnancy and predict its outcome as early as possible, allowing
      for modification of monitoring and treatment if required. Ultrasound examination
      is part of the routine follow-up after in vitro fertilization, but a gestational
      sac is not reliably visible until 33-37 days after ovulation induction. As a
      result, there is an ongoing effort to find endocrine markers that can earlier
      detect the establishment of pregnancy and forecast its outcome. OBJECTIVE: The
      authors' aim was to assess the predictive value of the following potential serum
      markers, measured in the second week after embryo transfer in samples collected
      prospectively during the past ten years at the Division of Assisted Reproduction
      of their department: total beta-hCG (theoretical post-embryo transfer day 11
      values, calculated from levels in two samples collected with a difference of two
      days, based on the mathematical model describing its exponential increase in
      early pregnancy), inhibin A, and CA-125. METHODS: Data of patients undergoing IVF
      or intracytoplasmic sperm injection and embryo transfer between 1995 and 2001
      were analyzed. Establishment of pregnancy was assessed by measuring total beta
      hCG concentrations in two serum samples collected between 8 and 16 days after ET
      with a difference of two days. Measurement of inhibin A and CA-125 levels was
      performed in the same samples. Logistic regression analyses were used to study
      the association of these serum markers and the number of retrieved oocytes and
      transferred embryos with pregnancy outcome. Receiver-operating characteristic
      (ROC) curves were constructed to identify optimal cutoff levels for outcomes and
      to assess overall predictive accuracy. RESULTS AND CONCLUSIONS: (1) Day 11 total
      beta-hCG can be used to compare hCG levels in samples from different sampling
      days and to predict early pregnancy losses and multiple ongoing pregnancies with
      high sensitivity and specificity. (2) Inhibin A concentrations are more accurate
      than day 11 hCG levels for predicting preclinical abortion after IVF but they
      have no advantage in forecasting ongoing or multiple ongoing pregnancies. (3)
      Prognostic accuracy of CA-125 measurements for the prediction of pregnancy as
      well as its outcome is inferior to that achieved with inhibin A.

PMID- 16977780
TI  - [Myopathy associated with respiratory insufficiency: diagnostic difficulties in
      adult-onset Pompe disease].
AB  - INTRODUCTION: Adult-onset acid maltase deficiency myopathy is a rare lysosomal
      storage disease with an autosomal recessive pattern of inheritance. The disease
      can be manifested with respiratory insufficiency and fatigue. METHODS: A case of
      a 45-year-old male patient is presented, and difficulty in diagnosis is
      discussed. RESULTS: The patient had been repeatedly examined because of
      hypersomnia, dyspnea and fatigue for a full year before a neurological
      consultation was requested. Artificial ventilation resulted in a dramatic
      improvement of his symptoms. Neurological examination revealed myopathy.
      Electrophysiological myotonia and glycogen storage in muscle biopsy specimen
      suggested acid maltase deficiency. The diagnosis was established by genetic
      testing detecting the previously described homozygous c.-45T > G mutation in the
      alpha-glucosidase gene. DISCUSSION: Rare hereditary neurological diseases can be
      also suspected as cause of chronic unexplained respiratory insufficiency resulted
      in hypersomnia and fatigue due to hypercapnia and myopathy. A proper diagnosis
      can contribute to early diagnosis and introduction of enzyme replacement therapy
      may reduce or stop clinical progression. Genetic diagnosis can also provide a
      possibility for prenatal testing.

PMID- 16977781
TI  - [My master Artur Hamori].

PMID- 16977782
TI  - [Medical attendance in Budapest for the casualties of the 1956 revolution].

PMID- 16977783
TI  - [Pathophysiologic role of myocardial hypertrophy, microcirculatory dysfunction
      and cardiomyocyte apoptosis in aortic stenosis].
AB  - The burden of aortic stenosis is increasing steadily and, despite major advances
      in diagnosis and management, surgical valve replacement is still the only
      effective treatment. Most recently, experimental studies in animals and clinical
      studies in humans have shown that myocardial hypertrophy, microcirculatory
      dysfunction and cardiomyocyte apoptosis are among the central pathophysiologic
      mechanisms involved in the natural history of aortic stenosis, i.e. the passage
      from a compensated and hypertrophic heart to a dysfunctional heart prone to
      ischemia, arrhythmia and pump failure. This updated review emphasizes the
      promises of these new research avenues as well as their potential therapeutic
      applications.

PMID- 16977784
TI  - [Off-pump coronary bypass surgery: pros and cons].
AB  - Off-pump coronary artery bypass surgery is a well established surgical option for
      patients candidate to coronary artery bypass. Current evidence suggests that
      there are no differences between off-pump and on-pump coronary surgery in terms
      of major perioperative outcomes such as perioperative mortality, myocardial
      infarction, stroke, and renal failure, whereas off-pump coronary surgery seems to
      reduce some minor complications like atrial fibrillation, transfusion
      requirements, and postoperative hospital stay. However, some recent papers
      suggest that graft patency may be lower for grafts performed with the off-pump
      technique. In this paper we review current knowledge about pros and cons of off
      pump and on-pump coronary bypass surgery.

PMID- 16977785
TI  - [Surgical treatment of chronic thromboembolic pulmonary hypertension with
      pulmonary endarterectomy].
AB  - Acute pulmonary embolism is the third most common cardiovascular disease in Italy
      with approximately 65 000 new cases a year. Appropriate medical therapy does not
      necessarily prevent evolution of acute pulmonary embolism into chronic
      thromboembolic pulmonary hypertension (CTEPH), which occurs in 0.1-4.0% of cases.
      In our country, there are approximately up to 2600 new CTEPH patients a year.
      CTEPH is a progressive and potentially lethal disease. Medical therapy is
      palliative and only surgery can modify its natural history. Pulmonary
      endarterectomy (PEA) is the treatment of choice and lung transplantation should
      be considered only when PEA is contraindicated. Currently, nearly 4000 PEAs have
      been performed worldwide. Approximately ten centers are able to carry out this
      intervention with excellent and permanent results. Solid experience and close
      multidisciplinary collaboration allow appropriate patient selection, rigorous
      surgical technique, and adequate postoperative management. All these aspects
      represent the key to the success in the treatment of CTEPH. After PEA, quality
      and expected length of life are similar to the age-matched general population and
      the only therapy required is oral anticoagulation.

PMID- 16977786
TI  - [Ischemic postconditioning: an effective strategy of myocardial protection?].
AB  - Post-ischemic reperfusion worsens myocardial injury. Ischemic preconditioning
      limits the damage by ischemia and reperfusion. Both adenosine and nitric oxide
      (NO) pathways are involved in protection. Preconditioning, however, is of little,
      if any, practical use as the onset of an infarction is usually unpredictable.
      Recently, it has been shown that the heart can be protected against the extension
      of reperfusion injuries if 3 or 4 brief (10-30 s) coronary occlusions are
      performed just at the beginning of the reperfusion. This procedure has been
      called post-conditioning. Post-conditioning reduces the oxidant-induced injury;
      moreover, it attenuates the local inflammatory response to reperfusion. Post
      conditioning also activates triggers, signaling pathways and effectors implicated
      in other cardioprotective maneuvers, such as ischemic and pharmacological
      preconditioning. Post-conditioning seems to trigger the up-regulation of survival
      kinases principally known to attenuate the pathogenesis of apoptosis and possibly
      necrosis. As regards the possibility of pharmacological post-conditioning,
      several agents have been tested. We are testing NO donor(s), which can reduce
      infarct size in the rat in the absence of post-conditioning. Since during
      reperfusion there is a large production of reactive oxygen species, also the
      effect of administration of an antioxidant compound during reperfusion was
      studied. In the rat, such a procedure reduced the infarct size to a greater
      extent than post-conditioning. Moreover, an additive effect of NO donors and
      antioxidant compounds is possible.

PMID- 16977787
TI  - [Myocardial infarction with normal coronary arteries: a condition with multiple
      etiology and variable prognosis].
AB  - Myocardial infarction with angiographically normal coronary arteries was
      recognized more than 30 years ago. Since then, various series of patients with
      such condition have been described, but the etiology and pathogenesis still
      remain a matter of debate. Evidence exists for a role of coronary vasospasm,
      thrombosis, embolization and inflammation, per se or combined, in determining the
      occurrence of myocardial infarction with angiographically normal coronary
      arteries. Endothelial dysfunction, possibly superimposed to non-angiographically
      evident atherosclerosis, may be an underlying common feature predisposing to the
      acute event. Additionally, myocarditis may explain some of these occurrences.
      Myocardial infarction with normal coronary arteries is therefore likely to be the
      result of multiple pathogenetic mechanisms. Although most reports emphasize the
      good prognosis of this condition, in general much better than myocardial
      infarction with coronary artery disease, prognosis is likely variable according
      to the underlying mechanism. This review summarizes current knowledge on this
      condition and examines areas of recent progress.

PMID- 16977788
TI  - [Occupational and leisure time physical activity: trend in the Italian
      population].
AB  - BACKGROUND: Over the last decades a change in physical activity habits of the
      Italian population has been observed. The aim of this study was to compare
      occupational and leisure-time physical activity, to assess the relationship
      between physical activity and cardiovascular risk factors and the variation in
      cardiovascular risk profile measured 20 years apart in the Italian population.
      METHODS: In two populations aged 35-69 years (MATISS 1984-1987: 2041 men, 2424
      women; OEC 1998-2002: 4214 men, 4206 women) gender-specific levels of
      occupational (occupational physical activity [OPA]-light, OPA-moderate, OPA
      heavy) and leisure-time (leisure-time physical activity [LTPA]-low, LTPA
      moderate, LTPA-high) physical activity were compared. Relationship between
      physical activity and cardiovascular risk factors was evaluated in the two
      samples using logistic regression models adjusted for age, heart rate,
      educational level and other possible confounding variables in men and women
      separately. The 10-year cardiovascular risk was assessed in the two periods and
      in different physical activity strata using the Progetto CUORE risk score.
      RESULTS: Comparing the two studies, prevalence of OPA-low had decreased, whereas
      the prevalence of LTPA-low had increased. With increasing LTPA blood pressure,
      heart rate and glycemia decreased, whereas high-density lipoprotein-cholesterol
      increased with a positive effect on obesity, smoking habit and cardiovascular
      risk. CONCLUSIONS: Over the last 20 years, physical activity apparently changed:
      currently men and women dedicate more time to physical activity during leisure
      time, and are less active at work. More active people have lower levels of major
      cardiovascular risk factors. Societal efforts are needed to increase physical
      activity levels in the population.

PMID- 16977789
TI  - [PROVA E TRASPORTA Project: results of tele-transmission of the electrocardiogram
      from community hospitals and emergency service ambulances in the management of ST
      elevation acute coronary syndromes].
AB  - BACKGROUND: Availability of a telematic system of electrocardiogram (ECG)
      transmission may improve the management of ST-elevation myocardial infarction
      (STEMI), by reducing time to treatment. The aim of this study was to show the
      effectiveness of telephone transmission of ECG in improving quality of care for
      patients with acute STEMI. METHODS: Since January 1, 2003, we activated a
      management program of STEMI in healthcare district of Varese, located in the
      North-West of Lombardy (Italy), comprising one fourth-level hospital, equipped
      with a cath lab on call 24/24 h for primary angioplasty since 1993 and cardiac
      surgery, and 2 community hospitals, placed in a mountain area approximately 30 km
      far from Varese. The emergency medical system (EMS) transport was activated 24/24
      h and has 15 basic life support (BLS) ambulances with trained nurse staff and 2
      mobile units with medical staff, all of them equipped with semiautomatic
      defibrillator Lifepack 12, enabling a GSM telephone transmission of a 12-lead
      ECG, coupled with 3-lead continuous rhythm recording and clinical data, if
      necessary. The ECGs were transmitted to a core unit placed in the coronary care
      unit (CCU) of the Hospital di Circolo of Varese, directly connected with the EMS
      core unit. RESULTS: From January 2003 to August 2005, a total of 2063 ECGs were
      transmitted, 538 of them (26%) recorded by EMS ambulances. Of 144 ECGs (7%)
      showing a persistent ST-elevation suggesting an acute STEMI (group A), 112
      subjects underwent reperfusion: 73 were treated with angioplasty and 39 by lysis
      alone. By comparing data of group A with a group of 256 patients (180 reperfused)
      with acute STEMI, admitted to our hospital in the same period without ECG
      teletransmission (group B), we observed no statistical difference in mortality
      and reperfusion rates but a significative reduction in the pre-hospital and in
      hospital times in group A patients treated by primary angioplasty and
      thrombolysis. CONCLUSIONS: Our study confirms previous results in that an early
      availability of a 12-lead ECG, transmitted from peripheral community hospitals
      and BLS ambulances, is able to reduce time to management of patients with an
      acute STEMI, thus improving quality of decision-making and treatment.

PMID- 16977790
TI  - [Cyclooxygenase inhibitors: a never ending story?].

PMID- 16977791
TI  - [Implantable defibrillators--economic and legal aspects of biotechnology].

PMID- 16977792
TI  - Postinflammatory hyperpigmentation: evolving combination treatment strategies.
AB  - Postinflammatory hyperpigmentation (PIH) is a common acquired excess of pigment
      in the epidermal and/or dermal layers of the skin. Lesions persist for extended
      periods if untreated, thus therapy is warranted. Topical monotherapies include
      the standard bleaching agent hydroquinone (HQ) as well as retinoids. Recently,
      several fixed-dose combination products were introduced to the armamentarium: HQ
      4%-retinol 0.15% in a microsponge formulation; HQ 4%-retinol 0.3%; mequinol 2%
      tretinoin (RA) 0.01%; and fluocinolone acetonide (FA) 0.01%, HQ 4%, and RA 0.05%.
      Recent findings have suggested that mequinol 2%-RA 0.01% solution is a promising
      alternative for the treatment of PIH.

PMID- 16977793
TI  - The role of DNA methylation in cancer development.
AB  - Epigenetic modifications include DNA methylation and covalent modification of
      histones. These alterations are reversible but very stable and exert a
      significant impact on the regulation of gene expression. Changes in methylation
      of promoter or first exon may mimic the effect of mutations of various tumor
      suppressor genes (TSGs) or protooncogenes. Carcinogenesis can also result from
      aberrations in genomic DNA methylation that include hypermethylation and
      hypomethylation of promoter or first exon of cancer-related genes.
      Hypermethylation of promoter of various TSGs causes their transcriptional
      silencing. However, hypomethylation of regulatory DNA sequences activates
      transcription of protooncogenes, retrotransposons, as well as genes encoding
      proteins involved in genomic instability and malignant cell metastasis. The
      methylation of genomic DNA in malignant cells is catalyzed by DNA
      methyltransferases DNMT1 and DNMT3B, revealing significantly elevated expression
      in different types of cancers. The reversibility of hypermethylation can be used
      as target of therapeutic treatment in cancer. DNMT 1 and DNMT3B inhibitors
      including 5-Aza-2'-deoxycytidine and antisense oligonucleotides have been applied
      in clinical trials of such treatment. Identification of aberrations of DNA
      methylation in cancer cells is a new field of investigation in carcinogenesis. We
      believe that epigenetic cancer diagnostic and therapy will be achieved in the
      next decades.

PMID- 16977794
TI  - SDF-1 alone and in co-operation with HGF regulates biology of human cervical
      carcinoma cells.
AB  - Stromal Derived Factor-1 (SDF-1)-CXCR4 axis plays a pivotal role in biology and
      metastasis of several tumors. The aim of this study was to see if SDF-1 alone or
      in combination with Hepatocyte Growth Factor (HGF) affects biology of human
      cervical carcinoma (HCC) cells. We found that HCC cell lines investigated in our
      study highly express CXCR4 on their surface. CXCR4 was also expressed on tumor
      cells in tissue sections derived from cervical cancer patients. At the same time
      normal cervical epithelium was negative for CXCR4 expression what suggests a
      strong correlation between CXCR4 and malignant cell phenotype. Subsequently, we
      studied a potential role of the SDF-1-CXCR4 axis in HCC and noticed that SDF-1
      (i) chemoattracted HCC cells, (ii) enhanced their scattering, (iii) stimulated
      nuclear localization of beta-catenins and upregulated their target gene cyclin D1
      and (iv) at the molecular level induced calcium flux and activated RAS-MAPK, PI3
      AKT and JAK-STAT pathways. SDF-1-mediated functions were additionally enhanced in
      the presence of HGF. Thus, our data show that the SDF-1-CXCR4 axis affects
      biology of HCC cells. Furthermore, we postulate that this axis might become a
      potential target to prevent progression of cervical cancer.

PMID- 16977795
TI  - Immunohistochemical expression of androgen receptor and prostate-specific antigen
      in breast cancer.
AB  - AR (androgen receptor) and PSA (prostate-specific antigen) are involved in the
      pathogenesis of breast cancer, but their role is not clearly defined. The purpose
      of this study was to analyze by immunohistochemistry the AR and PSA (prostate
      specific antigen) expression in 156 female breast carcinomas and to correlate the
      results with some histopathological parameters, like ER (estrogen receptor), PR
      (progesterone receptor), HER2/neu, nodal and metastasis status, histological type
      and grade. ARs and PSA were expressed in 112/156 (72%) and respectively in 61/156
      (39%) of cases and we found a positive correlation between AR and PSA expression
      in breast carcinomas (p<0.0002). We also found an association between the
      histological type of the tumor and AR (p<0.001), respectively PSA (p=0.01) and
      between AR and the grade of differentiation (p=0.007) and the nodal status
      (p=0.02). No correlations were found between the metastasis status and AR or PSA.
      47.3% (53/112) of AR-positive cases and 46% (28/61) of PSA-positive cases were ER
      negative. High frequency of AR (87.5%) and PSA (75%) expression was found in
      medullary carcinomas and 53% of lobular invasive carcinomas co-expressed AR and
      PSA. We found an inverse correlation between HER2/neu and PSA (p=0.05). Although
      most of the PSA-positive carcinomas were lymph node-negative, well and moderately
      differentiated, we did not find any statistically significant correlations
      between these parameters and PSA expression. Our study confirms that ARs are
      commonly expressed in breast cancer and the expression of PSA and AR are highly
      correlated. Moreover, all the lobular carcinomas and the majority of medullary
      carcinomas co-expressed AR and PSA, the majority of AR-positive carcinomas were
      lymph node-negative, well and moderately differentiated, and large number of ER
      negative carcinomas expressed AR and PSA.

PMID- 16977796
TI  - Immunohistochemical detection of angiotensin receptors AT1 and AT2 in normal rat
      pituitary gland, estrogen-induced rat pituitary tumor and human pituitary
      adenomas.
AB  - Male rat pituitary glands, diethylstilbestrol (DES)-induced rat pituitary tumors
      and 12 human pituitary adenomas were immunostained with antibodies raised against
      AT1 and AT2 angiotensin receptor proteins. Positive immunostaining of AT1 was
      observed in a subpopulation of anterior and intermediate pituitary lobe cells as
      well as in some nerve endings of the neurohypophysis. In the DES-induced rat
      pituiary tumors, the subpopulation of AT1-immunnopositive cells was smaller than
      in the non-tumoral anterior pituitary. In human pituitary adenomas, weak AT1
      immunostaining was found in 5 tumors. In the remaining adenomas, the AT1
      immunostaining was trace (doubtful) or absent. The AT1 immunostaining in the
      peritumoral non-neoplastic pituitary tissue was stronger than that observed in
      the tumors. The normal rat pituitaries and rat tumors did not show immunostaining
      with anti-AT2 antibody. In human pituitary adenomas, the tumoral cells were AT2-
      negative but moderate to strong AT2 immunostaining was observed in intratumoral
      blood vessel walls. The data suggest that the experimental (in rat) and
      spontaneous (in man) pituitary tumorigenesis is associated with the down
      regulation of AT1 receptors. The expression of AT2 receptors, in turn, may be
      connected with the process of tumoral neo-angiogenesis.

PMID- 16977797
TI  - A false expression of CD8 antigens on CD4+ T cells in a routine flow cytometry
      analysis.
AB  - The two-colour flow cytometry method applied in a routine enumeration of
      peripheral blood T lymphocyte subsets reveals that in some patients the entire
      population of CD4+ lymphocytes seems to express CD8 determinants as well.
      However, expression of the CD8 antigens on the cell surface is much lower in
      comparison with typical CD8+ cells. Moreover, in one-colour staining with an anti
      CD8 antibody, cells with weak CD8 expression are not observed and only one
      typical population of CD8+ lymphocytes is seen. Investigating this phenomenon, we
      showed that after washing patient cells in RPMI before CD4/CD8 staining, the CD4+
      T cell population did not show CD8 "co-expression". These results suggest that
      CD4+ lymphocytes, which seem to co-express CD8 antigen, in fact do not have this
      antigen on their surface. Moreover, after the addition of patient plasma to
      healthy donor cells prior to CD4/CD8 staining, a weak CD8 expression on normal
      CD4+ cells was noticed. Therefore we can assume that the agent(s) causing this
      phenomenon is/are present in the plasma of some patients. Altogether, these
      observations suggest that this phenomenon is nonspecific and probably results
      from cross-linking of anti-CD8 mAbs with anti-CD4 mAbs caused by factor(s)
      present in plasma of some patient. However, identification of that/these
      factor(s) requires further research.

PMID- 16977798
TI  - Androgen receptor in early apoptotic follicles in the porcine ovary at pregnancy.
AB  - Localization of androgen receptor (AR) was investigated in ovarian follicles
      developing and undergoing atresia during pregnancy in the pig.
      Immunohistochemical staining was conducted on ovarian antral follicles isolated
      on different days of gestation: 10, 18, 32, 50, 70, and 90. Paraffin sections
      were also subjected to in situ DNA labeling. TUNEL staining revealed the presence
      of positive follicles on all days of pregnancy but the amount of atretic
      follicles increased with time. However, even on day 90 of gestation many
      follicles were normal, with no signs of atresia. In atretic follicles, apoptotic
      cells were localized predominantly in the granulosa while theca was much less
      affected. Atretic follicles with many apoptotic cells were negative for AR.
      Nuclear immunostaining for AR was positive in follicles with limited amount of
      apoptotic cells. The same relationship was observed in ovarian follicles isolated
      at various days of pregnancy.

PMID- 16977799
TI  - Sources of porcine longissimus dorsi muscle (LDM) innervation as revealed by
      retrograde neuronal tract-tracing.
AB  - The aim of the present study was to establish the origin of the motor, autonomic
      and sensory innervation of the L1-L2 segment of the porcine longissimus dorsi
      muscle (LDM), in order to provide morphological basis for further studies
      focusing on this neural pathway under experimental conditions, e.g. phototerapy
      and/or lateral electrical surface stimulation. To reach the goal of the study,
      multiple injections of the fluorescent neuronal tracer Fast Blue (FB) were made
      into the LDM region between the spinal processes of the vertebrae L1 and L2. The
      spinal cord (Th13-S1 segments) as well as the sensory and autonomic ganglia of
      interest, i.e., dorsal root (DRG) and sympathetic chain ganglia from
      corresponding spinal cord levels were collected three weeks later. FB-positive
      (FB+) motoneurons were observed exclusively within the nucleus ventromedialis at
      L1 and L2 spinal cord level, forming the most ventro-medially arranged cell
      column within this nucleus. Primary sensory and sympathetic chain neurons were
      found in appropriate ipsilateral ganglia at Th15-L3 levels. The vast majority of
      retrogradely traced neurons (virtually all motoneurons, approximately 76% of
      sensory and 99.4% of sympathetic chain ganglia neurons) was found at the L1 and
      L2 levels. The morphometric evaluation of FB-labeled DRG neurons showed that the
      majority of them (approximately 66%) belonged to the class of small-diameter
      perikarya (10-30 microm in diameter), whereas those of medium size (30-80 microm
      in diameter) and of large diameter (more than 80 microm) constituted 22.6% and
      11.5% of all DRG neurons, respectively. The results of the present study
      demonstrated that the nerve terminals supplying porcine LDM originated from
      different levels of the spinal cord, dorsal root and sympathetic chain ganglia.
      Thus, the study has revealed sources and morphological characteristic of somatic,
      autonomic and spinal afferent neurons supplying porcine LDM, simultaneously
      pointing out the characteristic features of their distribution pattern.

PMID- 16977800
TI  - Expression of metallothionein in renal tubules of rats exposed to acute and
      endurance exercise.
AB  - The induction of exercise-induced apoptosis in not actively involved in exercise
      organs, such as kidney could be a result of oxidative stress. Metallothionein
      (MT) exerts a protective effect in the cell against oxidative stress and
      apoptosis. We have previously demonstrated an increased incidence of apoptosis in
      distal tubular cells and collecting ducts in rat kidney after acute exercise. The
      present study was designed to test the hypothesis that MT may play a protective
      role in rat renal tubules against exercise-induced apoptosis after the acute
      exercise and regular training. Male Wistar rats were divided into control, acute
      exercised and 8-wk regularly trained groups. The kidneys were removed after a
      rest period of 6 h and 96 h. The ultrastructure of renal tubular cells was
      examined by electron microscopy. Apoptosis was detected in paraffin sections by
      the TUNEL technique. Expression of MT was examined by immunohistochemistry. The
      level of lipid peroxidation (thiobarbituric acid reactive substances - TBARS) was
      assayed in renal tissue homogenates. After acute exercise, the occurrence of
      apoptosis was restricted to distal tubules and collecting ducts of rat kidney,
      whereas the proximal tubules remained unaffected. The 8-wk training did not
      result in increased apoptosis in tubular cell. MT expression was confined
      exclusively to proximal tubules in all groups. However, it was significantly
      increased in acutely exercised animals, as compared to control and trained rats.
      After the 8-wk training, MT expression remained unaltered as compared to the
      control group. TBARS levels were significantly increased after acute exercise,
      while after regular training they remained unchanged. A significant correlation
      between TBARS level and MT expression was demonstrated. The findings could
      suggest a protective role of MT against oxidative stress and apoptosis in
      proximal tubular cells.

PMID- 16977801
TI  - Is the repair of articular cartilage lesion by costal chondrocyte transplantation
      donor age-dependent? An experimental study in rabbits.
AB  - The repair of chondral injuries is a very important problem and a subject of many
      experimental and clinical studies. Different techniques to induce articular
      cartilage repair are under investigation. In the present study, we have
      investigated whether the repair of articular cartilage folowing costal
      chondrocyte transplantation is donor age-dependent. Transplantation of costal
      chondrocytes from 4- and 24-week old donors, with artificially induced femoral
      cartilage lesion, was performed on fourteen 20-week-old New Zealand White male
      rabbits. In the control group, the lesion was left without chondrocyte
      transplantation. The evaluation of the cartilage repair was performed after 12
      weeks of transplantation. We analyzed the macroscopic and histological appearance
      of the newly formed tissue. Immunohistochemistry was also performed using
      monoclonal antibodies against rabbit collagen type II. The newly formed tissue
      had a hyaline-like appearance in most of the lesions after chondrocyte
      transplantation. Positive immunohistochemical reaction for collagen II was also
      observed in both groups with transplanted chondrocytes. Cartilage from adult
      donors required longer isolation time and induced slightly poorer repair.
      However, hyaline-like cartilage was observed in most specimens from this group,
      in contrast to the control group, where fibrous connective tissue filled the
      lesions. Rabbit costal chondrocytes seem to be a potentially useful material for
      inducing articular cartilage repair and, even more important, they can also be
      derived from adult, sexually mature animals.

PMID- 16977802
TI  - Morphometric and functional abnormalities of kidneys in the progeny of mice fed
      chocolate during pregnancy and lactation.
AB  - Even most commonly consumed beverages like tea, coffee, chocolate and cocoa
      contain methylxanthines, biogenic amines and polyphenols, among them catechins,
      that exhibit significant biological activity and might profoundly affect the
      organism homeostasis. We have previously shown that 400 mg of bitter chocolate or
      6 mg of theobromine added to the daily diet of pregnant and afterwards lactating
      mice affected embryonic angiogenesis and caused bone mineralization disturbances
      as well as limb shortening in 4-weeks old offspring. The aim of the present study
      was the morphometric and functional evaluation of kidneys in the 4-weeks old
      progeny mice fed according to the protocol mentioned above. Progeny from the mice
      fed chocolate presented considerable morphometric abnormalities in the kidney
      structure, with the lower number of glomeruli per mm2 and their increased
      diameter. Moreover, higher serum creatinine concentration was observed in that
      group of offspring. No morphometric or functional irregularities were found in
      the progeny of mice fed theobromine. Abnormalities demonstrated in the offspring
      of mice fed chocolate are not related to its theobromine content. Consequently,
      identification of active compound(s) responsible for the observed effects is of
      vital importance.

PMID- 16977804
TI  - Urothelial neoplasia of the urinary bladder--comparison of interobserver
      variability for WHO Classification 1972 with WHO/ISUP Consensus Classification
      1998.
AB  - BACKGROUND: Classification of urothelial bladder tumours is an important factor
      in the treatment and prognosis of these lesions. Over the years many
      classifications have been proposed for this purpose. The objective of this study
      was to classify urothelial neoplasms of the urinary bladder using the latest
      WHO/ISUP Consensus Classification 1998 and WHO Classification 1972 and compare
      the two regarding interobserver variability. METHODS: This study included 100
      consecutive biopsy specimens of urothelial neoplasms of the urinary bladder
      diagnosed at the department of Histopathology, Armed Forces Institute of
      Pathology, Rawalpindi. These were classified according to WHO Classification 1972
      and WHO/ISUP Consensus Classification 1998 by 2 groups of pathologists
      independently. The tumour categories for WHO classification 1972; papilloma, and
      transitional cell carcinoma (TCC) grades I, II and III were compared with the
      WHO/ISUP Consensus Classification entities of papilloma, papillary neoplasm of
      low malignant potential, low grade and high grade papillary carcinomas. Kappa
      statistics were used to evaluate interobserver variability. Chi square test was
      used to calculate significance. RESULTS: There was agreement on 80 tumours
      between the two groups of histopathologists when using WHO classification 1972
      while there was agreement on 95 tumours using WHO/ISUP consensus classification.
      The value of Kappa for WHO Classification was 0.68 (good agreement) whereas for
      WHO/ISUP Consensus Classification it was 0.91 (excellent agreement). The
      difference between the two systems was statistically significant (p<0,001). Kappa
      values were less for benign and borderline lesions using both systems.
      CONCLUSIONS: WHO/ISUP Consensus Classification 1998 showed less interobserver
      variability than WHO Classification 1972 in the evaluation of bladder tumours. It
      was found easier to apply by both groups. There was less agreement on the benign
      and borderline lesions using both the classifications.

PMID- 16977805
TI  - Characteristics of dengue fever in a large public hospital, Jeddah, Saudi Arabia.
AB  - BACKGROUND: This study aims to determine demographic, clinical and laboratory
      profile along with disease outcome of all confirmed cases of dengue fever (DF)
      and dengue hemorrhagic fever (DHF) admitted in King Abdulaziz Hospital & Oncology
      Center, Jeddah, Saudi Arabia. We also want to highlight the significance of
      implementing a well targeted community based disease prevention program. METHODS:
      All patients admitted from May 2004 till April 2005 with a suspected diagnosis of
      DF and DHF were followed. All cases confirmed by a positive serology (IgM alone
      or IgM and IgG) to dengue fever were studied in detail to determine age, gender,
      ethnicity, monthly distribution, clinical and laboratory profile. RESULTS: A
      total of 80 patients were admitted with a suspected diagnosis of DF. Among these,
      39 (48.75%) patients were confirmed by positive serology to have the disease.
      Male to female ratio was 3.3:1. Their ages ranged from 2 to 60 years with a mean
      of 27.6 +/- 11.2. Twelve patients were Saudis, while the rest were non-Saudis
      coming from different countries in Asia, Africa and Middle East. Maximum number
      of patients (48.72%) was seen in the summer months of June, July and August.
      Commonest presentation was fever (100%), headache (48.72%), myalgias (66.7%) and
      vomiting (25.64%). Rash, hemorrhagic manifestations and positive tourniquet test
      were relatively uncommon. Only two patients fulfilled WHO criteria of DHF. Main
      hematological abnormalities were thrombocytopenia (79.49%) and leucopenia
      (48.72%). Significant elevation of PTT was observed in 25.64% of patients.
      Abnormal liver function tests with high transaminases were seen in about 66.7% of
      patients, whereas 33.33% of patients had significantly elevated creatine kinase.
      All patients improved clinically with improvement of chemical and hematological
      parameters. None of the patients died in this series. CONCLUSION: DF continues to
      be a significant health problem in Western region of Saudi Arabia. Large number
      of pilgrims coming from disease endemic areas all over the world facilitates the
      continued introduction of dengue virus with different strains. Fortunately there
      has been no serious outbreak of dengue fever in recent years. A sharp vigilance
      is required by concerned authorities to prevent and minimize any future outbreak.
      It is extremely important to implement and maintain an effective, sustainable and
      community based disease prevention program.

PMID- 16977806
TI  - An analysis of surgically managed cases of pelvic abscess complicating unsafe
      abortion.
AB  - BACKGROUND: This study was carried out to study the demographic variables,
      treatment options and mortality in cases of abortion related pelvic abscess.
      METHODS: A retrospective study of patients that had pelvic abscess as a
      complication of unsafe abortion. The retrieved case files were scrutinized for
      the necessary information. RESULT: The age ranged from thirteen years to forty
      six years, and teenagers accounted for 24.3% of the patients. About half of the
      patients, 51.4% were childless and parity ranged from zero to eight. The
      abortionists were mainly untrained personnel and the contraceptive prevalence
      rate was low, 5.4%. Most of the patient had conservative surgery and a
      significant number 94.6%, had blood transfusion. Maternal death of 18.9% was
      recorded with infection being the major cause. CONCLUSION: Unsafe abortion and
      its attendant complication is still a problem in Nigeria. High quality post
      abortion care will help a long way in saving many lives.

PMID- 16977807
TI  - Hyperventilatory capacity--a predictor of altitude sickness.
AB  - BACKGROUND: The aim of the study was to document link between hyperventilatory
      capacity and risk for developing acute mountain sickness (AMS). METHODS: This
      study was carried out at Karakorum Mountain ranges (Northern areas of Pakistan)
      from March till July 2004. 54 healthy male subjects were enrolled in this study.
      Arterial oxygen saturation (SpO2) of the subjects was measured by the pulse
      oximeter at rest and after 1 minute of voluntary hyperventilation at an altitude
      of 2833 meters. Symptoms of acute mountain sickness (AMS) were recorded on a
      questionnaire by using the Lake Louise consensus scoring system 24 hours after
      ascent to high altitude. RESULTS: Mean pre hyperventilation oxygen saturation
      (SpO2) was 94.07 + 0.26% whereas SpO2 after 01 minute of hyperventilation was
      98.61 + 0.14% that was significantly increased (p<0.001). The mean increase in
      percent oxygen saturation of hemoglobin after one minute of hyperventilation
      (hyperventilatory capacity) for the study group was 4.61 +/- 0.24 % while the
      mean symptom score was 2.06 +/- 0.26. It was noted that 19 (35.2%) subjects did
      not develop AMS whereas 34(63.0%) subjects had mild AMS and only one subject
      developed moderate AMS. There was no case of severe AMS. The data reveals
      significant (P<0.01) association between hyperventilatory capacity and
      development of the symptoms of AMS (r = -0.664). It is evident that individuals
      with greater hyperventilatory capacity manifest less number of symptoms of
      mountain sickness. CONCLUSION: It is concluded that post hyperventilation
      increase in oxygen saturation at lower altitude may help to predict the
      susceptibility of subjects to develop high altitude sickness.

PMID- 16977808
TI  - Clinical features and outcome of cerebral abscess in congenital heart disease.
AB  - BACKGROUND: Cerebral abscess is a serious life threatening complication of
      several diseases. The objective of this study was to look at the clinical
      profile, microbiology and outcome of children with cerebral abscess having an
      underlying congenital heart disease as compared to other predisposing conditions.
      METHODS: Thirty children aged less than 15 years were reviewed. There were 15
      males and 15 females. The mean age of presentation was 5.6 +/- 4.4 years.
      RESULTS: The duration of illness at the time of admission was 17.6 +/- 24.6 days.
      Typically patients presented with fever, vomiting, headache and seizures. The
      predisposing conditions found were cyanotic congenital heart disease in 11 (37%)
      of children, meningitis in 6 (20%), septicemia in 7 (23%) and no underlying cause
      was found in 5 (17%) children. The most common microbe in children with cyanotic
      congenital heart disease was of the Streptococcus milleri group (52%).
      Computerized tomography confirmed the diagnosis and the most common location of
      the abscess was the parietal lobe of the cerebral hemisphere. All abscesses were
      large, more than 2 cm in diameter and were aspirated surgically. Excision was
      performed in 6 children. Five children expired, one due to a intracranial
      bleeding and the others due to severe cerebral edema and tentorial herniation.
      Complications were seen in 20 children and 16 had sequelae, hemiparesis in 11 and
      seizure disorder in 5. CONCLUSION: Brain abscess is a serious infection with poor
      outcome if diagnosed late. Delayed surgical drainage has high morbidity and
      mortality. The threshold for diagnosis should be low particularly in children
      with a predisposing condition like cyanotic congenital heart disease.

PMID- 16977809
TI  - Peripheral blood-based polymerase chain reaction in diagnosis of pulmonary
      tuberculosis.
AB  - BACKGROUND: The rapid diagnosis of infectious diseases, particularly those that
      represent a public health problem, like tuberculosis, is a challenging problem.
      By using nucleic acid amplification techniques like PCR, one may be able to
      diagnose, the disease on the day of arrival of specimen in the laboratory. For
      diagnosis of tuberculosis by direct methods like PCR, specimens from site of
      infection are required. In certain cases it is difficult to get the specimens
      from site of infection and in such situations; some researchers have tried to
      detect the DNA of Mycobacterium tuberculosis complex from blood of these
      patients. The purposive of this study is to determine the diagnostic efficacy of
      peripheral blood-based polymerase chain reaction for diagnosis of pulmonary
      tuberculosis. METHODS: This was a simple descriptive study, carried out in
      Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi from
      Jan 2004 to Dec 2004. Sputum and blood samples were collected from 96 suspected
      patients of pulmonary tuberculosis. Sputum samples processed for ZN staining and
      AFB culture (gold standard) and blood samples processed for PCR. RESULTS: Out of
      96 cases, 60 (62.5%) were culture positive. PCR was positive in 14 (14.5%). AFB
      smear positive were 34 (35.4%). The overall sensitivity and specificity of the
      PCR assay was 20% and 94.4% respectively and the positive and negative predictive
      values were 85.71% and 41.46% respectively. The overall efficiency of the test
      was 47.91%. CONCLUSION: Due to low sensitivity; a negative PCR assay does not
      rule the disease. However, this test may be helpful in cases where specimens from
      the site of infection are not available.

PMID- 16977810
TI  - High growth hormone levels in clinically short stature children.
AB  - BACKGROUND: Growth Hormone (GH) is secreted from the anterior pituitary gland. It
      binds to receptors on the surface of target cells, stimulates production of
      Insulin-like growth factor-I (IGF-I) leading to growth of almost all tissues of
      the body capable of growing. Growth failure (height below 3rd centile) occurs in
      children who do not secrete sufficient amount of GH. In some children, however,
      short stature is present in the presence of high levels of GH in their blood and
      they also secrete normal to increased amounts of GH in response to stimulation
      tests when tested for possible deficiency of GH. This condition is known as GH
      resistance syndrome or Larons syndrome (LS). METHODS: All patients after a
      thorough clinical evaluation underwent GH evaluation protocol as follows. On
      arrival in the lab a blood sample was collected for basal GH level in each
      patient. Screening was performed by subjecting the patients to exercise
      stimulation test and/or L-dopa stimulation test. Patients with GH deficiency
      underwent insulin tolerance test (ITT) after one week for confirmation. All the
      basal and post-stimulation samples were analyzed for GH levels. A level below
      10mIU/L indicated GH deficiency, between 10-20mIU/L as borderline and an adequate
      response was defined as a GH >20mIU/L. Patients with a basal GH level of >20mIU/L
      and/or a post-stimulation level of >40mIU/L were arbitrarily considered as having
      exaggerated GH levels. This article evaluates the high plasma growth hormone
      levels among clinically short stature children undergoing growth hormone
      stimulation tests. RESULTS: Two hundred ninty-three patients reported for GH
      evaluation. Twenty were excluded for various reasons. Thus 273 patients were
      included for GH evaluation out of which 66(24.2%) showed GH deficiency, 89(32.6%)
      were borderline while 118(43.2%) patients exhibited adequate response, with GH
      levels of >20mIU/L. A number of patients unexpectedly showed very high GH levels
      on screening tests. Out of 118 patients, 21 showed either very high basal levels
      of >20mIU/L and/or a much-exaggerated response to stimulation tests with levels
      more than about 40mIU/L. Close consanguinity was found in 67% of patients showing
      very high GH levels. CONCLUSION: Some children with idiopathic short stature may
      show high levels of GH during their evaluation for GH deficiency. We identified a
      considerable number of such patients. These patients require further
      investigations.

PMID- 16977811
TI  - Sonomammography for evaluation of solid breast masses in young patients.
AB  - BACKGROUND: This study was carried out to evaluate the applicability of
      sonomammography as the primary radiological modality in young patients with
      breast masses. METHODS: This study was carried out at Radiology Departments of
      PNS Shifa Karachi and CMH Rawalpindi from February 2002 to April 2005.
      Sonomammography of 56 young patients with breast lump was done. Lesions were
      characterised by using sonographic criteria as benign (n=49), malignant (n=2) and
      intermediate (n=5) masses. Results of this evaluation were assessed by fine
      needle aspiration cytology. RESULTS: No false positive result was noted in 49
      benign lesions while only one intermediate mass turned out to be malignant.
      Sensitivity of sonomammography was more for benign 92% than malignant lesions
      67%, and its specificity was high for malignant lesions 92.4%. Retrospective
      scanning was done for intermediate masses. CONCLUSION: This study proves the
      efficacy of ultrasound as a method of choice to evaluate breast masses in young
      patients avoiding the need of biopsy. This study also reflects that benign
      diseases dominate the disease spectrum in young patients.

PMID- 16977812
TI  - Significance of immunohistochemistry in accurate characterization of malignant
      tumors.
AB  - BACKGROUND: To determine in a large series of surgical biopsies the role and
      significance of immunohistochemistry in the adequate and accurate
      characterization of malignant tumors. METHODS: A retrospective study of 20,000
      consecutive surgical biopsies reported in the Section of Histopathology, AKU in
      2003. Data was obtained by retrieving the filed surgical biopsy reports in the
      section. RESULTS AND CONCLUSIONS: Out of the 20,000 biopsies, 6534 (32.67%) were
      neoplastic. 4726 neoplasms (72.33%) were malignant, and 1808 (27.67%) were
      benign. Immunohistochemistry was performed on 29.49% of malignant tumors, and
      4.97% of benign tumors. Immunos were performed on only 2.82% of routine squamous
      cell carcinomas and adenocarcinomas of various organs, and in only 1.9% of
      infiltrating breast carcinomas, the commonest malignant tumors in females. In
      contrast, immunos were performed on 97.12% of non-Hodgkin's lymphomas, 97.94% of
      Hodgkin's lymphomas, 98.09% of malignant spindle cell neoplasms, 87.96% of small
      round blue cell tumors of childhood, 87.30% of neuroendocrine neoplasms, and
      84.37% cases of malignant melanomas. In addition, immunos were performed on all
      cases of malignant undifferentiated neoplasms and were able to resolve the issue
      in over 89% of such cases. Immunos were also performed on 54.74% of metastatic
      tumors. Lymph nodes were the commonest organs on which immunos were performed
      i.e. 96.50% of lymph node tumors, followed by CNS and renal neoplasms with 33.01%
      and 25.92% respectively.

PMID- 16977813
TI  - Restoration of glenohumeral motion in Erb's palsy by tendon transfers.
AB  - BACKGROUND: Children with erb's palsy have significant functional disability,
      mainly related to the shoulder. The objective of this study was to analyze the
      functional outcome of tendon transfers performed for restoration of shoulder
      motion in patients with Erb's palsy. METHODS: This descriptive case series was
      conducted at Aga Khan University Hospital from May 1999 to December 2003. Ten
      patients who had functional deficit of shoulder elevation were operated by a
      single surgeon. The surgical procedure; modified Sever L'Episcopo procedure was
      uniform in all cases. The data was collected through patient interviewing and
      medical records maintained through Health Information Management System (HIMS).
      Mallet class was recorded preoperatively and postoperatively. RESULTS: Ten
      patients; seven females (70%) and three males (30%), with average age of 75
      months at operation were included in this series. Right shoulder was affected in
      seven cases (70%) while left in three cases (30%). Preoperative mallet class for
      global abduction improved from 3 to 4; for global external rotation from 2 to 4
      and for ability to bring the hand to mouth and neck from 1 to 3. Post operatively
      mallet class improved in all aspects to 4 and 5; statistically significant on
      paired t-test with p value of less than 0.005. There was a significant
      improvement in abduction, forward flexion and external rotation as compared to 
      preoperative values; statistically significant on paired t-test with p value of
      less than 0.005. CONCLUSION: Tendon transfer improves the functional status of
      shoulder in late cases of Erb's Palsy with significant improvement in mallet
      class, cosmesis and patient satisfaction. A motivated patient, compliance and
      aggressive rehabilitation are important outcome parameters.

PMID- 16977814
TI  - Comparative study of Mathieu and Snodgrass repair for anterior hypospadias.
AB  - BACKGROUND: This study was carried out to compare the operative time and rate of
      complications of Mathieu and Snodgrass procedures for the repair of primary
      anterior hypospadias. METHODS: This study was carried out in the Department of
      Pediatric Surgery, The Children hospital, Pakistan Institute of Medical Sciences
      Islamabad, from March 2003 to Feb 2005. We managed 90 patients with primary
      anterior hypospadias. Children between 2 years to 12 years were included in the
      study. Those who had previous repair were excluded from the study. Only those
      patients were selected who never had their hypospadias repaired. Those with
      significant chordee were also excluded from the study. Patients were divided into
      two groups. Group I had Mathieu repair and Group II had Tubularized Incised Plate
      (TIP) urethroplasty (Snodgrass procedure). Stent was kept patent by frequent
      irrigation. Operative time was calculated for both the procedures separately.
      Patients were followed for subsequent complications. RESULTS: A total of 90 cases
      were studied. Mathieu repair was performed in 45 patients and tubularized incised
      plate (TIP) urethroplasty (Snodgrass procedure) in the rest of 45 patients.
      Cosmetic results were excellent with Snodgrass repair with a normal looking slit
      like meatus. Meatal stenosis and wound breakdown was equal in each group whereas
      urocutaneous fistula and proximal urethral stricture were seen more frequently in
      Mathieu group.

PMID- 16977815
TI  - Effect of hypoproteinemia on treatment outcome in children with acute
      lymphoblastic leukemia.
AB  - BACKGROUND: Malnutrition is prevalent on large scale in hospitalized patients
      which increases morbidity and mortality, reduces the effectiveness of medical
      treatment in our hospitals and impairs the quality of life significantly. Early
      diagnosis and treatment of malnutrition is gaining the significance day by day.
      METHODS: A prospective study was carried out to assess the effects of
      hypoproteinemia malnutrition on the treatment outcome of children with acute
      lymphoblastic leukemia. One hundred and sixty three patients with Acute
      Lymphoblastic Leukemia (ALL) below the age of 14 years with L1 and L2 FAB
      morphology were included in this study. Treatment protocol used was FBM. Patients
      were classified according to Waterlow classifications of malnutrition (1976).
      Group-I, as Well-Nourished children (WNC) and Group-II as Mal-nourished children
      (MNC). Percentages in both groups were found out with respect to total expired,
      Relapses and completed treatment. RESULTS: In Group-I (WNC) 50 (81.96%) completed
      treatment and alive, 5 (8.19%) relapsed and 6 (9.8%) expired. In Group-II (MNC)
      31(30.39%) completed treatment and alive,8 (7.84%) relapsed and 63 (61.76%)
      expired. Overall, in WNC group-I 50(30.67%) completed treatment and alive, 5
      (3.07%) relapsed and 6(3.68%) expired. In MNC group-II 31 (19.02%) completed
      treatment and alive, 8 (4.91%) relapsed and 63 (38.65 %) expired. CONCLUSION:
      Hypoproteinemia affects treatment outcome in children with acute Lymphoblastic

PMID- 16977816
TI  - Combined abdominal hysterectomy, cholecystectomy and appendicectomy: a study of
      25 cases in Abbottabad.
AB  - BACKGROUND: Gallstone disease is common in women. Many patients undergoing
      abdominal ultrasound for gynaecological diseases are found to have gallstones.
      This study was done to see the results of combined abdominal hysterectomy, mini
      cholecystectomy and appendicectomy in a set up lacking facilities of laparoscopic
      surgery. METHODS: This prospective study was conducted in Ayub Teaching Hospital,
      Iltaf Hospital and Shahina Jamil Trust Hospital of Abbottabad from August 1998 to
      July 2004. All patients undergoing combined abdominal hysterectomy and mini
      cholecystectomy were exclusively studied with reference to following variables.
      Age, Weight, Parity, Co-morbid conditions, peri-operative and post-operative
      complications, blood transfusion, hospital stay and mean extra time for mini
      cholecystectomy and appendicectomy after abdominal hysterectomy. RESULTS: There
      were 25 patients in the study group. The ages ranged from 35-50 years. Mean
      weight was 65 Kg. There were no operative complications. Mild postoperative
      complications occurred in 7(28%) patients. Mean extra time for cholecystectomy
      was 25 minutes. Mean hospital stay was 9 days. CONCLUSIONS: In selected women,
      combined abdominal hysterectomy, cholecystectomy and appendicectomy is a safe,
      feasible and cost effective procedure.

PMID- 16977817
TI  - Etiology of strokes and hemiplegia in children presenting at Ayub Teaching
      Hospital, Abbottabad.
AB  - BACKGROUND: Strokes in pediatric age group are not common. However diagnosing the
      cause of stroke will help in providing preventive and curative treatment. Present
      study was conducted to find etiology of strokes/hemiplegia in children. METHODS:
      This study was conducted in Department of Pediatrics, Ayub Teaching Hospital
      Abbottabad from December 2002 to December 2005. All children from two months to
      fifteen years of age were included in the study. Children with weakness due to
      acute poliomyelitis and Guillan barre syndrome were excluded. Investigations were
      based on findings on history and clinical examination and included full blood
      count, PT, APTT, Platelets count, ECG, Echocardiography, hematocrit, lumber
      puncture with CSF analysis and culture and CT-scan skull. Data of all the
      patients presenting with strokes/hemiplegia was entered on prepared proforma.
      RESULTS: The main etiology of strokes was intracranial infection causing strokes
      in 23(56.09%)children and majority of children (78.26%) in this group were below
      five years. Etiology was un-known in 7(17.07%) children after necessary available
      investigations. CONCLUSIONS: Intracranial infection Infections that is meningitis
      and encephalitis are commonest etiology of strokes and hemiplegia in paediatrics
      patients presenting at Ayub Teaching Hospital, Abbottabad.

PMID- 16977818
TI  - An assessment study of maternal mortality ratio databank in five districts of
      North Western Frontier Province Pakistan.
AB  - BACKGROUND: Maternal mortality ratio is an indicator to measure the summary of
      information about mother and child health. It is estimated that about 500
      maternal deaths occur per 100,000 live births each year in Pakistan. It is a well
      known fact that all health statistics coming out of the developing countries are
      calculated "guesstimates" some are perhaps more close to the real figures than
      the others. There is a dire need to help generate information that can be used by
      health professionals, health care planners and managers to save women's lives by
      improving the quality of care provided to turn away maternal mortality. The
      maternal mortality ratio for Pakistan as well as for NWFP is projected as
      533/100,000 live births for the year 1990-91 produced by National Institute of
      Population Studies, Pakistan. METHODS: This was a retrospective cross-sectional
      quantitative study for the period (2001-2002) conducted in five districts of
      (NWFP) North Western Frontier Province, Pakistan. RESULTS: National HMIS data
      opened the maternal mortality ratio for; Haripur as 0.168 and 0.173, Mansehra 00
      and 00, Battagram 00 and 00, Swat 0.051. and 0.524 and Swabi 00 and 0.968
      per/1000 live births, respectively. The small part exercise outcome (the study)
      endorsed more shadowy side of the actual maternal mortality ratio for the same
      period in the same districts. CONCLUSION: In our country there is a urgent need
      to institute an efficient mode of operation to get accurate maternal mortality
      database. Verbal Autopsy method is cost effective and feasible approach for
      implementation in a country like Pakistan.

PMID- 16977819
TI  - Applications and complications of polyurethane stenting in urology.
AB  - BACKGROUND: As surgeons working in a developing country, we decided to review our
      experience with polyurethane stents instead of the more expensive ones on common
      urological procedures and analyzing our experience with respect to their
      usefulness versus their problems and outcome. METHODS: This stusy was carried out
      at Armed Forces Institute of Urology, Rawalpindi and Combined Military Hospital,
      Kharian Cantonment, Pakistan through March 2002 through May 2004. During this
      period 342 of patients were operated requiring stent and 220 patients out of
      these had polyurethane as stent material for different urological operations.
      RESULTS: Among the 220 patients who underwent polyurethane stenting, early
      complications included fever, infection, voiding symptoms while stent migration,
      encrustation and stent stiffness was encountered as later complications.
      CONCLUSION: The benefits of Polyurethane stents are its strength, versatility and
      low cost. Poor biodurability and biocompatibility only limit its use; these are
      reasonably effective in our setup but should only be used for short duration.

PMID- 16977820
TI  - Use of silastic as interpositional material in the management of unilateral
      temporomandibular joint ankylosis.
AB  - BACKGROUND: Ankylosis is a very common condition developed mainly after damage to
      mandibular condyles or temporomandibular joint (TMJ) at a growing age. Different
      autogenous and alloplastic interpositional materials have been attempted after
      the resection of the ankylotic bone to achieve desirable results. This condition
      is relatively common in Pakistan. We treated TMJ ankylosis with alloplastic
      medical grade silicone "silastic" interpositional arthroplasty. Eight joints
      accompanied ipsilateral or contralateral coronoidectomy to achieve desirable
      results. METHOD: All patients were presented at Punjab Dental Hospital Lahore.
      Sixty-one joints with unilateral TMJ ankylosis were underwent surgery after
      careful examination and final radiographic confirmation. The preoperative CT scan
      was also performed in few patients. RESULTS: The postoperative measurements of
      the interincisal opening with lateral and protrusive jaw movements were criteria
      for success of surgery. The lateral and protrusive jaw movements were assessed as
      excellent, good and poor. Less than 25 mm interincisal opening was considered as
      poor jaw opening. CONCLUSION: The overall success rate was 98.4 % with 84 %
      desirable interincisal jaw opening. Less than 5% patients were observed with poor
      jaw opening. The immediate late complications were transient and were included
      oedema, weakness of a branch of the facial nerve on the operated side. Two
      implants were infected along with one wire in the first month of surgery and were
      removed under local anaesthesia without further complication.

PMID- 16977821
TI  - Tension-free vaginal tape and female stress urinary incontinence. Our initial
      experience in Pakistan.

PMID- 16977822
TI  - Exuberant ulcerated lesions of secondary syphilis on the palms--an unusual
      presentation.
AB  - Ulcerated lesions in secondary syphilis are rare. Exuberant tissue is seen in
      condylomas of syphilis, which occur in flexural and occluded areas of the body
      and not in open areas such as palms. We report a case of secondary syphilis that
      presented with ulcerated exuberant lesions on palms, which on initial examination
      gave an impression of lesions of Orf and Milker's Nodule.

PMID- 16977823
TI  - A case of chronic liver disease. Hev induced or cryptogenic?
AB  - Hepatitis E virus (HEV) infection is known to cause epidemic outbreaks as well as
      sporadic disease in many parts of the world. Clinical presentation of hepatitis E
      varies from acute icteric viral hepatitis to severe disease with fulminant
      hepatic failure, and anicteric infection (no jaundice but with ALT elevation).
      According to available data HEV infection does not lead to chronic liver failure.
      We are reporting a case of 37 years old army soldier who was admitted as a case
      of HEV induced acute viral Hepatitis. Later he was found to have chronic liver
      disease (CLD) with persistence of HEV antibodies and absence of any other
      detectable cause of CLD.

PMID- 16977824
TI  - Parathyroid carcinoma.
AB  - Parathyroid carcinoma is a very rare cause of primary hyperparathyroidism and
      these tumors are usually hyper-functioning as compared to other malignant
      endocrine tumors. Surgery is the only effective primary treatment. We report a
      patient, who presented with pathological fracture of femur, hypercalcemia,
      bilateral renal stones, markedly raised Parathormone levels and palpable mass in
      the neck. Parathyroid adenoma was initially diagnosed and localized at left lower
      gland by Sestamibi scan and ultrasonography. She underwent surgery and enlarged
      parathyroid gland was removed. Intra operatively there was no evidence of local
      invasion or lymph nodes involvement but biopsy report suggested malignancy.

PMID- 16977825
TI  - Intracranial extra-skeletal mesenchymal chondrosarcoma.
AB  - Intracranial Mesenchymal Chondrosarcoma is a very rare and uncommon entity that
      affects young adults. We came across one such patient who presented with severe
      headache and intermittent nausea and vomiting. The clinical, radiological
      preoperative diagnosis was a meningioma, on histological examination it turned
      out to be mesenchymal chondrosarcoma of tentorial region in posterior fossa,
      uncommon site for this entity.

PMID- 16977826
TI  - Nonsurgical endodontic management of cutaneously draining odontogenic sinus.
AB  - Odontogenic cutaneous sinus tract is a rare but well documented condition. It is
      usually misdiagnosed as a local skin lesion and maltreated by systemic
      antibiotics and/or surgical excision with eventual recurrence. This is because
      the primary etiology is incorrectly determined. We came across a 38 year old
      patient who presented with a cutaneous lesion on her left cheek with frequent
      purulent discharge and was not responding to systemic antibiotics. The case
      history, diagnosis and management of this condition is presented here.

PMID- 16977827
TI  - Acute transverse myelitis in children.
AB  - A case of Acute Transverse Myelitis (ATM) is presented. ATM is a rare disease in
      childhood. The diagnosis stems from the clinical presentation, cerebrospinal
      fluid findings, appearance of the spinal cord on imaging and ruling out
      differential diagnoses like Guillain-Barre syndrome (GBS) and Poliomyelitis. The
      proposed treatment is intravenous (IV) methyl prednisolone with variable chances
      of recovery. A controlled multicenter study is suggested to assess epidemiology,
      etiology and prognosis of ATM.

PMID- 16977828
TI  - A unique management of tracheal stenosis.

PMID- 16977829
TI  - Spatial summation processes in the receptive fields of visually driven neurons of
      the cat's cortical area 21a.
AB  - The spatial summation in receptive fields (RF) of single neurons in cat's
      extrastriate area 21a was investigated as a basic neurophysiological substrate
      for central integration processing of visual information. The results showed that
      the majority of investigated neurons changed their response patterns with gradual
      increase of applied stimulus size. In approximately 82% of cases the suppression
      of neuron discharges was observed when the length of the moving strip exceeded
      that of the RF. In some neurons the increased size of the moving stimulus leads
      to the changes in the RF substructure. Receptive fields of neurons recorded at
      the same microelectrode penetration depth showed a great variety of RF
      superpositions distributed in a spatially asymmetric manner. As a result, every
      single RF consists of multiple sub-regions within the RF, differing from each
      other by the number of superimposed RF-s (density factor). We suggest that such
      complex spatial organization of the RF provides the neurophysiological basis for
      central integration processing of the visual information.

PMID- 16977830
TI  - Organization of bilateral spinal projections to the lateral reticular nucleus of
      the rat.
AB  - The present study was carried out to analyze the topography of bilateral spinal
      projections to the lateral reticular nucleus (LRN). We used retrograde transport
      of fluorescent tracers Fast Blue and Diamidino Yellow to identify spinal neurons
      projecting to the ipsilateral and/or contralateral LRN, as well as orthograde
      transport of Phaseolus vulgaris leucoagglutinin to identify the LRN areas where
      spinoreticular axons terminate. Orthograde labeling confirmed that bilateral
      spinoreticular projections coming from cervical and upper-thoracic segments
      terminate in the magnocellular division of LRN, while those coming from the lower
      thoracic, lumbar and sacral segments end in the parvocellular division of the
      nucleus; only a sparse spinal input has been observed in the subtrigeminal
      division of LRN. Retrograde labeling showed that labeled neurons were present at
      all spinal levels and in particular large numbers in the cervical and lumbar
      enlargements. Retrogradely single-labeled cells were located, with contralateral
      predominance, in all segments of the spinal cord, within laminae IV, V, VI, VIII,
      and X, whereas in laminae III and VII labeled neurons were mainly observed
      ipsilaterally. Furthermore, a small fraction of double-labeled cells (7.4%) was
      observed throughout the spinal cord, mainly in laminae III, IV, VII and VIII.

PMID- 16977831
TI  - Changes in the time course of potentiated and fatigued contractions of fast motor
      units in rat muscle.
AB  - The contraction and relaxation times of the twitches and the last contractions
      within 32 unfused tetani of FF and 27 unfused tetani of FR motor units in the rat
      medial gastrocnemius muscle were studied during prolonged activity. The pattern
      of the MU stimulation included single pulses (to evoke twitches) and series of
      three trains of stimuli at 40, 50 and 60 Hz (to evoke unfused tetani), repeated
      30 times. The analysis concerned changes of force and time parameters at the
      beginning of activity, during the potentiation and then during the fatigue. It
      was found that changes of force during the potentiation and the fatigue were
      mainly accompanied by changes in the course of relaxation. The significant
      prolongation of the half-relaxation time during the potentiation of either
      twitches or unfused tetani was revealed in both types of fast MU. The twitch
      contraction time did not change markedly, whereas significantly shortened in the
      last contractions of unfused tetani during the potentiation. These changes of
      time parameters correlated to the increase of the fusion degree. During the
      fatigue, the time parameters shortened, however, changes of the half-relaxation
      times were remarkably higher. The shortening of relaxation was responsible for
      the decrease of the fusion degree. Changes of the fusion index exceeding 0.75
      during the potentiation or decreasing below this value during the fatigue, were
      accompanied by respective appearance or disappearance of the biphasic relaxation.

PMID- 16977832
TI  - Aminergic control of neuronal firing rate in thalamic motor nuclei of the rat.
AB  - The effects induced on neuronal firing by microiontophoretic application of the
      biological amines noradrenaline (NA) and 5-hydroxytryptamine (5-HT) were studied
      "in vivo" in ventral-anterior (VA) and ventrolateral (VL) thalamic motor nuclei
      of anaesthetized rats. In both nuclei the amines had a mostly depressive action
      on neuronal firing rate, the percentage of units responsive to NA application
      (88%) being higher than to 5-HT (72%). Short-lasting (less than 2 min) and long
      lasting (up to 20 min) inhibitory responses were recorded, the former mostly
      evoked by NA and the latter by 5-HT ejection. In some cases 5-HT application had
      no effect on the firing rate but modified the firing pattern. NA-evoked responses
      were significantly more intense in VL than in VA neurons. Short-lasting
      inhibitory responses similar to NA-induced effects were evoked by the alpha2
      adrenergic receptor agonist clonidine and to a lesser extent by the beta
      adrenergic receptor agonist isoproterenol. Inhibitory responses to 5-HT were
      partially mimicked by application of the 5-HT(1A) receptor agonist 8-hydroxy-2(di
      n-propylamino)tetralin (8-OH-DPAT) and of the 5-HT2 receptor agonist alpha-methyl
      5-hydroxytryptamine (ALPHA-MET-5-HT). The latter evoked excitatory responses in
      some cases. Both 5-HT agonists were more effective on VA than on VL neurons. The
      effects evoked by agonists were at least partially blocked by respective
      antagonists. These results suggest that although both 5-HT and NA depress
      neuronal firing rate, their effects differ in time course and in the amount of
      inhibition; besides aminergic modulation is differently exerted on VA and VL.

PMID- 16977833
TI  - The vestibulo-ocular and the vestibulospinal reflexes: noradrenergic influences
      on the plastic changes which affect the cerebellar cortex during vestibular
      adaptation.

PMID- 16977834
TI  - A cautionary note on appropriate statistical methods to compare dose responses of
      methionine sources.

PMID- 16977835
TI  - Effects of formalin feeding or administering into the crops of white leghorn
      cockerels on hematological and biochemical parameters.
AB  - Formalin administered (15 and 20 mL) into the crops of White Leghorn cockerels
      resulted in behavioral alterations, included depression, dullness, staggering,
      somnolence, anorexia, and decreased frequency of crowing. A significant decrease
      was observed in red blood cell counts, hemoglobin concentration, packed cell
      volume, and leukocyte counts in birds fed higher levels of formalin. Decreasing
      and increasing trends in concentrations of serum proteins and enzymes,
      respectively, were observed with increases in formalin doses. Significantly lower
      blood glucose and testosterone levels and significantly (P < 0.05) higher blood
      urea and creatinine concentrations were observed in birds fed higher formalin
      levels. No gross or microscopic lesions were observed in the birds fed different
      levels of formalin mixed in feed. These changes suggested that the formalin mixed
      in feed might have evaporated, and, hence, the amount ingested might have been
      too low to induce pathological changes. It was concluded from the present study
      that formalin mixed up to 5 mL/kg of feed, corresponding to 10 mL/bird of 3%
      formalin in drinking water by crop tube had no adverse effects on the health of
      White Leghorn cockerels.

PMID- 16977836
TI  - Responses of thyroid hormones of market-size broilers to thermoneutral constant
      and warm cyclic temperatures.
AB  - This study characterizes the responses, particularly diurnal variations, of
      thyroid hormones (TH) [3,5,3'-triiodothyronine (T3), thyroxine (T4), and T3:T4
      ratio (T3/T4)] of Arbor Acres broilers to constant thermoneutral (TN) or warm
      cyclic (WC) temperatures. There existed distinct circadian variations--2 peaks in
      TH under the TN and WC conditions. The 2 peaks of T3, T4, and T3/T4 of the
      broilers occurred, respectively, at 0 and 16 h, 8 and 16 h, and 0 and 12 h under
      the TN condition; but at 0 and 12 h, 0 and 8 h, and 4 and 12 h under the WC
      conditions. During a 5-d heat exposure (HE) to the WC regimens, T3 and T4 showed
      continual decrease. The daily mean of T3 declined significantly (P < 0.05) on the
      first day of HE, whereas significant decrease of T4 (P < 0.05) occurred on the
      second day of HE. There was no significant change in daily mean of T3/T4 during
      the same HE period. Hence, results of the study indicate that T3 provides a
      better heat stress indicator than T4. The nature of circadian variations in TH
      makes it necessary to collect blood samples more than once a day, e.g., 6 times
      at 0, 4, 8, 12, 16, and 20 h, to ensure full evaluation of hormonal responses of
      market-size broilers undergoing thermal challenges.

PMID- 16977837
TI  - Effect of on-farm litter acidification treatments on Campylobacter and Salmonella
      populations in commercial broiler houses in northeast Georgia.
AB  - Two commercially available litter treatments, aluminum sulfate and sodium
      bisulfate, were tested to determine their effect on Campylobacter and Salmonella
      levels associated with commercial broilers during a 6-wk grow-out period. A total
      of 20 broiler houses at 10 different locations were studied; 5 aluminum sulfate
      treated houses, 5 sodium bisulfate-treated houses, and 10 paired, untreated
      control houses. A single application rate was investigated for each treatment.
      Fecal samples (n=20 per house) were analyzed at wk 2, 4, and 5 and 6 for
      Campylobacter and Salmonella. The results indicated that, at the application
      rates investigated, both acidifying litter treatments caused a slight delay in
      the onset of Campylobacter colonization in broiler chicks. Salmonella levels
      remained unaffected, with no significant effect seen with either treatment (P >
      0.05). Campylobacter populations and Salmonella incidence associated with
      unprocessed, whole-carcass rinse samples (n=10 per house) analyzed at the end of
      production (wk 5 and 6) were unaffected by treatment.

PMID- 16977838
TI  - Feed withdrawal alters small-intestinal morphology and mucus of broilers.
AB  - In an effort to reduce carcass contamination and consequent reprocessing, market
      age broilers are often subjected to feed withdrawal (FW) before processing to
      reduce intestinal content and intestinal ruptures during processing. However,
      little is known regarding the effects of FW on mucus content and intestinal
      morphology. Therefore, 2 experiments were conducted to determine the effects of
      FW on intestinal characteristics. Male broilers were raised in floor pens on
      standard industry diets to 42 and 39 d of age for Experiments (Exp.) 1 and 2,
      respectively. In Exp. 1, feed was removed 24, 12, 8, and 0 h before sampling,
      respectively (n = 5 birds/time). Birds remained on litter with access to water
      for the first 4-h of the FW period and were then placed in crates. Body weights,
      left pectoralis major weights, and distal ileal and jejunal segments were
      collected for determination of morphological characteristics. For Exp. 2, birds
      (n = 8 birds/time) were subjected to 0, 12, and 24 h of FW. Birds were injected
      with 5-bromo-2'-deoxyuridine and thymidine at 24 and 21 h, respectively, before
      sampling to determine epithelial cell migration rates. One-centimeter distal
      ileal segments were collected for mucus quantification at 0, 12, and 24 h. In
      Exp. 1, ileal villi heights were unaffected by FW, but villus width and crypt
      depth decreased with increasing FW time (P < or = 0.05). Jejunal villus height
      increased as FW progressed. Jejunal crypt depths increased until 12 h of FW and
      then declined at 24 h. Mucus content decreased linearly and was reduced by 46%
      from 0 to 24 h FW (P < 0.05). The intestinal morphology alterations and the
      depletion of intestinal mucus that occur during a short-term FW may reduce the
      integrity of the intestine.

PMID- 16977839
TI  - Effects of feeding grains naturally contaminated with Fusarium mycotoxins on
      performance and metabolism of broiler breeders.
AB  - A study was conducted to investigate the effects of feeding grains naturally
      contaminated with Fusarium mycotoxins on performance and metabolism of broiler
      breeders. Forty-two 26-wk-old broiler breeder hens and nine 26-wk-old roosters
      were fed the following diets: (1) control, (2) contaminated grains, and (3)
      contaminated grains + 0.2% polymeric glucomannan mycotoxin adsorbent (GMA) for 12
      wk. The major contaminant was deoxynivalenol (12.6 mg/kg of feed), with lesser
      amounts of zearalenone and 15-acetyl-deoxynivalenol. Feed consumption and BW were
      not affected by diet. The feeding of contaminated grains did not significantly
      affect egg production. Decreased eggshell thickness was seen, however, at the end
      of wk 4, and dietary supplementation with GMA prevented this effect. There was no
      effect of diet on other egg parameters measured. There was a significant increase
      in early (1 to 7 d) embryonic mortality in eggs from birds fed contaminated
      grains at wk 4, but mid- (8 to 14 d) and late- (15 to 21 d) embryonic mortalities
      were not affected by diet. There were no differences in newly hatched chick
      weights or viability. The ratio of chick weight to egg weight was not affected by
      the feeding of contaminated grains. Weight gains of chicks fed a standard broiler
      starter diet at 7, 14, and 21 d of age were not significantly affected by
      previous dietary treatments for the dam. It was found that rooster semen volume
      and sperm concentration, viability, and motility were not affected by the feeding
      of contaminated diets. There was no effect of diet on the relative weights of
      liver, spleen, kidney, and testes. The feeding of contaminated grains decreased
      antibody titers against infectious bronchitis virus at the end of wk 12, and this
      was prevented by dietary supplementation with GMA. There was no effect of the
      diet on serum antibody titers against Newcastle disease virus. It was concluded
      that the feeding of blends of grains contaminated with Fusarium mycotoxins could
      affect performance and immunity in broiler breeder hens.

PMID- 16977840
TI  - Genetics of growth and reproduction in the turkey. 16. Effect of repeated
      backcrossing of an egg line to a commercial sire line.
AB  - The turkey industry's view of the relative economic importance of growth and egg
      production has changed rapidly, and genetic changes by selection within lines may
      not be rapid enough to meet the changing needs. The objective of the present
      study was to determine the feasibility of rapidly increasing the BW of dam lines
      by repeated backcrossing of a dam line (E) to a commercial sire line (B). The
      experimental E line was selected long-term for increased egg production and was
      used as the model for a turkey dam line. The B line was larger (more than 3-fold)
      in BW at 8, 16, and 20 wk of age, had wider breasts (approximately 1.8-fold) at
      16 wk of age, and had lower egg production for 180 d (about 3-fold) than the E
      line. Based on additive genetic variation, males in the F1 generation of the B x
      E cross did not differ from expected in BW at any age, but females of this cross
      had BW less than expected at 16 and 20 wk of age. In the F1 generation, breast
      width of the cross did not differ from the expected value, but egg production for
      180 d was greater than expected (126.6 vs.102.3 eggs/hen). After 3 generations of
      backcrossing, the backcrosses exhibited a gain in 20-wk BW of 12.5 and 8.8 kg,
      respectively, for males and females; a gain of 5.9 and 5.3 cm in breast width at
      16 wk of age for males and females, respectively; and a loss of 74.1 eggs per hen
      over a 180-d production period. Based on the results of the current and a
      previous study, limited backcrossing of a dam line to a sire line may be an
      economically feasible method to greatly increase the BW of dam lines without
      unduly sacrificing egg production. For maximum gains per generation, backcrossing
      probably should be used for a maximum of 2 or 3 generations.

PMID- 16977841
TI  - Association of twelve immune-related genes with performance of three broiler
      lines in two different hygiene environments.
AB  - Elite populations of farm animals under genetic selection are often maintained in
      high hygiene conditions, yet the commercial populations may be raised in, and are
      expected to perform well in, environments of varied hygiene levels. This presents
      special challenges to genetically improve those traits for which genotype by
      environment interactions are important. Twelve immune-related genes were studied
      for associations with general mortality and other performance traits in 3 elite
      commercial broiler chicken lines raised in high and low hygiene environments. The
      genes were toll-like receptor 4, MD-2 (accessory' protein of TLR4), interferon
      gamma, transforming growth factor-beta3, inducible nitric oxide synthase,
      macrophage migration inhibitory factor, interleukin-2, caspase-1, inhibitor of
      apoptosis protein-1, tumor necrosis factor-related apoptosis-inducing ligand,
      chicken B-cell marker, and bone morphogenetic protein-7. From a total of 56
      identified single-nucleotide polymorphisms (SNP) in 12 genes, 14 SNP that had
      moderate allelic frequencies in at least 2 of the 3 lines were typed in about 100
      progeny-tested sires from each of 3 elite commercial broiler chicken lines using
      restriction fragment length polymorphism techniques and then used in association
      analysis. The traits measured on the progeny (total progeny = 145,467) were:
      mortality from hatching to 14 d and from 14 to 40 d of age, BW at 7 and 40 d of
      age, feed conversion, ultrasound breast depth, percentage of breast, eviscerated
      carcass weight, twisted legs or evident tibial dyschondroplasia, x-ray-inspection
      based subclinical or incipient development of tibial dyschondroplasia, curly or
      crooked toes or bowed legs, oxygen content of blood, and female's antibody titer
      to infectious bursal disease virus at 27 wk. Association analyses were conducted
      with allele and haplotype substitution effect models using progeny mean data
      adjusted for fixed and mate effects as sire trait records. Ten of the 12 genes
      had SNP associations with at least 1 trait. Most detected effects were with
      mortality and growth traits. Most gene-SNP trait associations varied by genetic
      line or with environment. These results indicate that associations of candidate
      genes with important broiler traits can be identified in multiple environments,
      and they offer a potential for the implementation of marker-assisted selection
      for traits expressed in the environment in which the commercial broiler needs to
      perform. The effects of these immune-related candidate genes, however, are
      complex and affected by genetic background and environment.

PMID- 16977842
TI  - Bacteriocins reduce Campylobacter colonization and alter gut morphology in turkey
      poults.
AB  - Campylobacter is a leading cause of food-borne illness in the United States.
      Recent evidence has demonstrated that bacteriocins produced by Bacillus circulans
      and Paenibacillus polymyxa reduce cecal Campylobacter colonization in broiler
      chickens infected with Campylobacter jejuni. As Campylobacter coli is the most
      prevalent Campylobacter isolate recovered in turkeys, the objectives of the
      present study were to evaluate the efficacy of these bacteriocins against C. coli
      colonization and their influence on the gastrointestinal architecture of young
      turkeys. In 3 separate trials, a total of 135 day-of-hatch poults (n = 45/trial)
      were orally challenged on d 3 with approximately 10(6) cfu of a mixture of 3 C.
      coli isolates. Immediately before bacteriocin treatment (d 10), cecal
      Campylobacter concentrations averaged 1.1 x 10(7) cfu/ g of cecal contents (n =
      15/trial). On d 10 to 12 posthatch, 2 bacteriocin treatment groups were given
      free access to feed supplemented with purified, microencapsulated bacteriocins,
      whereas the positive control treatment group had access to untreated feed (n =
      10/treatment group per trial). At the end of the 3-d dosing period, ceca and
      duodenal loops were collected for analysis. In each of the 3 separate trials,
      treatment with bacteriocin eliminated detectable ceca Campylobacter
      concentrations (detection limit, 1 x 10(2) cfu/g of cecal contents) vs. controls
      (1.0 x 106 cfu of Campylobacter/g of cecal contents). Duodenum crypt depth and
      goblet cell numbers were also reduced in turkeys treated with either bacteriocin
      vs. controls (P < 0.05). The dynamic reduction in crypt depth and goblet cell
      density in turkeys dosed with bacteriocin may provide clues to how bacteriocins
      inhibit enteric Campylobacter.

PMID- 16977843
TI  - In vitro and in vivo assessment of humic acid as an aflatoxin binder in broiler
      chickens.
AB  - The in vitro affinity and adsorption capacity of a humic acid, oxihumate, for
      aflatoxin B1 (AFB1) was evaluated, utilizing Langmuir and Freundlich adsorption
      isotherms. Oxihumate showed a high in vitro affinity for AFB1. The Freundlich
      isotherm fitted the data better than the Langmuir isotherm, and binding
      capacities of 10.3, 7.4, and 11.9 mg of AFB1/g of oxihumate at pH 3, 5, and 7,
      respectively, were calculated. The in vivo efficacy of oxihumate as an aflatoxin
      binder in male broiler chickens exposed to aflatoxin-contaminated feed from 7 to
      42 d of age was also assessed. The efficacy of oxihumate was compared with a
      commercially available product with a brewers dried yeast (BDY) and brewers
      fermentation solubles as main active ingredients. A total of 420 birds were
      assigned to 28 pens, with 15 birds per pen. The following treatments were
      applied: 1) 0 mg of AFB1 + 0 additives, 2) 1 mg of AFB1/kg of feed + 0 additives,
      3) 1 mg of AFB1/kg of feed + 3.5 g of oxihumate/kg of feed, 4) 1 mg of AFB1/kg of
      feed + 3.5 g of BDY/kg of feed, 5) 2 mg of AFB1/kg of feed + 0 additives, 6) 2 mg
      of AFB1/kg of feed + 3.5 g of oxihumate/kg of feed, and 7) 2 mg of AFB1/kg of
      feed + 3.5 g of BDY/kg of feed. Each treatment consisted of 4 replicates.
      Oxihumate was effective in diminishing the adverse effects caused by aflatoxin on
      BW of broilers (P < 0.05). Oxihumate also showed protective effects against liver
      damage, stomach and heart enlargement, as well as some of the hematological and
      serum biochemical changes associated with aflatoxin toxicity (P < 0.05). Results
      indicated that oxihumate, but not BDY, could alleviate some of the toxic effects
      of aflatoxin in growing broilers. Oxihumate might, therefore, prove to be
      beneficial in the management of aflatoxin-contaminated feedstuffs for poultry
      when used in combination with other mycotoxin management practices. Additional
      studies are warranted to assess its efficacy under a wide variety of
      circumstances.

PMID- 16977844
TI  - Effects of supplementing broiler breeder diets with organoselenium compounds and
      polyunsaturated fatty acids on hatchability.
AB  - The effects of supplementing broiler breeder diets with polyunsaturated fatty
      acids (PUFA) and organoselenium compounds on fertility, hatchability, and the
      weight of 1-d-old chicks was assessed. Prepeak (23 wk) and peak (27 wk)
      production breeders were fed 1 of 4 diets: a wheat-based commercial breeder diet
      with 55 g/kg of either soybean oil (SO) or fish oil (FO), but no added Se (only
      that originating from feed ingredients), and each diet with added Se as Sel-Plex
      (SO + Se, FO + Se). The diets were designed to contain <0.1 mg/kg of Se and about
      0.5 mg/kg of Se for the nonsupplemented (no added Se) and the supplemented diets,
      respectively. The Se concentration of the eggshell of the hatching egg was
      measured. The concentration of Se, PUFA, and total lipid content of the brain and
      liver of the 1-d-old chick was determined. The number of fertile eggs increased,
      embryonic mortality decreased, and hatchability increased as hen age increased
      from 23 to 27 wk. The Se concentration in the eggshell and the brain and liver of
      1-d-old chicks was higher in the high-Se treatments com pared with the
      concentration in the low-Se treatments. Fish oil inclusion in the breeder diet
      increased embryonic mortality in wk 3 of incubation and reduced both hatchability
      and 1-d-old chick weight in hens of both ages. The addition of Se to the FO diets
      ameliorated some of these adverse effects, because chicks hatched from eggs laid
      by 23-wk-old breeders of the FO + Se treatment were heavier than those receiving
      the FO treatment. The Se concentration in the brain and liver of chicks from the
      FO hens was higher than that in chicks from the SO hens. The concentration of
      docosahexaenoic fatty acid was higher in the liver of chicks from the SO + Se
      treatment compared with that of chicks from the SO treatment, indicating possible
      protective effects of Se. Hatchability was decreased by increased PUFA and was
      higher in 27-wk-old compared with 23-wk-old breeders.

PMID- 16977845
TI  - Effect of arginine:lysine ratios and source of methionine on growth and body
      protein accretion in acutely and chronically heat-stressed broilers.
AB  - The effect of Arg:Lys, Met source, and time of exposure to heat stress on growth
      and body protein accretion was tested in acutely heat-stressed (AHS) or
      chronically heat-stressed (CHS) broilers. Ross 308 1-day-old chickens were raised
      under normal brooding conditions from 1 to 25 d of age and were then suddenly
      moved to 32 degrees C (AHS), whereas another group was kept at constant high
      temperatures throughout the grow-out period (32 degrees C; CHS). From 26 to 33 d
      of age, both groups were therefore at 32.8 +/- 1.0 degree C. Two rooms were used
      per environmental treatment. A basal diet deficient in TSAA was supplemented with
      L-Arg monohydrochloride to achieve Arg:Lys ratios of 0.95 and 1.40. Diets were
      supplemented with either L-Met, 2-hydroxy-4-(methylthio) butanoic acid (HMB), or
      DL-Met (DLM) to a level of TSAA 5% lower than requirements. Each Arg:Lys and Met
      source combination was diluted with a N-free diet to achieve graded levels of CP
      (0.0, 3.5, 7.0, 10.5, 14.0, and 17.5% CP) and fed to 18 replicates of 3 chickens
      (3 replicates per level). Treatment effects were obtained by the slope-ratio
      technique using average daily BW gain and body CP deposition as dependent
      variables and protein intake as the independent variable. Protein utilization
      remained unaffected by Met source when fed at high Arg:Lys for birds under AHS
      and CHS (P > 0.05). However, lower protein utilization was observed in birds fed
      L-Met in low Arg:Lys compared with those fed DLM (P < 0.05). Birds fed HMB at low
      Arg:Lys utilized dietary protein better than those fed L-Met only under CHS
      conditions (P < 0.05). Protein utilization for birds fed HMB was similar to that
      of birds fed DLM in all instances. It was concluded that Arg:Lys, Met source, and
      time of exposure to heat stress affected protein utilization in hyperthermic
      birds.

PMID- 16977846
TI  - Effects of conjugated linoleic acid supplementation in layer diet on fatty acid
      compositions of egg yolk and layer performances.
AB  - Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers
      of linoleic acid with conjugated double bonds. Conjugated linoleic acids have
      been reported to have a wide range of health-beneficial effects, including
      anticarcinogenic, antiatherogenic, antidiabetic, and immune stimulatory effects.
      The objective of this study was to investigate the incorporation of CLA into
      eggs. Three hundred 27-wk-old layers were allocated to 5 dietary treatments (0,
      1, 2, 3, and 4% CLA) with 5 replicates. The results of the study showed that
      average daily feed intakes were similar in all treatment groups, although hens
      fed with 4% CLA tended to consume less feed than other hens. Body weight gain and
      mortality rate were not significantly different (P > 0.05). Hens fed 4% dietary
      CLA had reduced egg, yolk, and albumen weights (P < 0.05). Yolk color
      significantly decreased as dietary CLA increased (P < 0.01). Shell thickness and
      Haugh units were not influenced by the dietary CLA. Concentrations of CLA and
      saturated fatty acids in egg yolk lipids increased as dietary CLA increased (P <
      0.01), whereas concentrations of monounsaturated fatty acids and polyunsaturated
      fatty acids decreased as dietary CLA increased (P < 0.01). It can be concluded
      from the present experiments that increasing the amount of CLA fed to hens will
      increase the amount of CLA in egg yolk and that this increase is accompanied by a
      reduction in the amount of yolk polyunsaturated fatty acids but an increase in
      yolk saturated fatty acids. Egg size, yolk weight, and Roche-fan determined yolk
      color significantly decreased at the highest level of CLA supplementation.

PMID- 16977847
TI  - Maternal organo-selenium compounds and polyunsaturated fatty acids affect progeny
      performance and levels of selenium and docosahexaenoic acid in the chick tissues.
AB  - The effects of supplementing broiler breeder diets with polyunsaturated fatty
      acids (PUFA) and organo-Se compounds on the levels of Se and PUFA in chick
      tissues and on chick performance were assessed. Prepeak (23 wk) and peak (27 wk)
      production broiler breeders were fed 1 of 4 diets: a wheat-based commercial diet
      with soybean oil or fish oil but no added Se, and each diet with added Se as Sel
      Plex (soybean oil + Se, fish oil + Se; Alltech Inc, Nicholasville, KY). The diets
      were designed to contain less than 0.1 mg of Se/kg and about 0.5 mg/kg for the
      nonsupplemented and the supplemented diets, respectively. As-hatched chicks from
      the 4 parental treatments were fed a nutritionally high quality diet (ME = 12.57
      MJ/kg; CP = 228.7 g/kg) or a low quality diet (ME = 10.28 MJ/kg; CP = 182.8
      g/kg), resulting in 8 dietary treatments. Performance was better and mortality
      lower in chicks from 27-wk-old breeders compared with those from 23-wk-old
      breeders. Fish oil in the maternal diet increased progeny mortality and reduced
      chick body mass at hatch. Body mass at 7 and 14 d posthatch was lower in chicks
      fed the low quality diet compared with chicks fed the high quality diet. At
      hatch, and for up to 14 d posthatch, chicks from hens fed diets high in PUFA had
      higher concentrations of docosahexaenoic acid (DHA) in the brain and liver
      compared with chicks hatched from hens fed diets low in PUFA. The DHA content of
      the tissues of chicks from breeders fed diets supplemented with Se was higher
      than that in chicks from breeders fed unsupplemented diets. Even after 14 d of
      being fed a diet with identical levels of Se, chicks hatched from parents fed
      diets high in Se had higher tissue Se concentrations than those hatched from
      parents fed diets low in Se. Supplementation of the maternal diet of chicks with
      organo-Se appears to enhance the DHA concentration of the chick brain, which may
      improve brain function.

PMID- 16977848
TI  - The effect of dietary probiotic supplementation on tibial bone characteristics
      and strength in broilers.
AB  - A 6-wk study with 50 birds was conducted to investigate the effects of a dietary
      supplemental probiotic on morphometric parameters and yield stress of the tibia.
      Twenty-five 1-d-old broiler chicks were assigned to a control or an experimental
      diet containing Bacillus licheniformis and Bacillus subtilis (BioPlus 2B, CHR
      Hansen BioSystems, Denmark, Ugur Ecza Deposu, Turkiye Distributoru, Adapazari
      41400, Turkey; each containing 2.3 x 10(8) cfu/g of spores) supplemented to the
      starter and finisher diets at 500 g/1000 kg of feed. Each diet was replicated 5
      times with 5 birds in each replicate. Tibiotarsi weight, length, and
      weight/length index, robusticity index, diaphysis diameter, modulus of
      elasticity, yield stress parameters, and percentage Ca content were not affected
      by the dietary supplementation of probiotic, whereas thickness of the medial and
      lateral wall of the tibia, tibiotarsal index, percentage ash, and P content were
      significantly improved by the probiotic. Medullary canal diameter of the tibia of
      the birds fed the control diet was significantly greater than that of birds fed
      the probiotic diet. There was no treatment impact on live performance of the
      birds throughout the 6-wk feeding trial.

PMID- 16977849
TI  - Semiautonomous development of the extraembryonic membranes in the chicken embryo.
AB  - Based on an old paradigm that the extra-embryonic membranes develop
      semiautonomously from the embryo, it can also be postulated that subembryonic
      fluid (SEF) will be formed semiautonomously against embryonic growth, because the
      formation of SEF is mediated by the yolk sac membrane. In this study, we
      interfered in the development of SEF or the embryo. The acoustic resonance
      technique (which measures the resonant frequency of an excited egg) was used as a
      nondestructive tool to monitor the development of SEF. In the first experiment,
      in which the embryo was killed chemically with NaN3, it was proven that the
      formation of SEF continued, even when the embryo was killed after the initiation
      of the growth of the yolk sac membrane. In the second experiment, in which the
      development of SEF was inhibited chemically with amiloride, it was shown that the
      embryo developed further, although SEF formation was inhibited. In the last
      experiment, it was shown that the age of the flock affected the development of
      the embryo and the sudden decrease of the resonant frequency in a different way.
      However, some presetting conditions, such as storage, may affect both in a
      similar way. Our results further strengthen the idea that the formation of SEF
      develops semiautonomously against embryonic development by using the
      nondestructive acoustic resonance technique as an indirect method to monitor yolk
      sac membrane formation.

PMID- 16977850
TI  - Use of a vascular access port for the measurement of pulsatile luteinizing
      hormone in old broiler breeders.
AB  - Techniques used to measure circulating hormone concentrations in avian species
      over extended periods routinely involve cannulation or multiple venipunctures
      under physical restraint, resulting in sepsis and stress. We adapted a method for
      serial blood sampling in chickens using a vascular access port (VAP) surgically
      implanted under the skin of the neck and connected to a catheter inserted in the
      right jugular vein. The system was used to measure circulating luteinizing
      hormone (LH) profiles in six, 21-mo-old broiler breeders at the end of their
      laying period. The VAP were implanted under general anesthesia, and, after a
      period of recovery, serial blood samples (every 10 min for 6 h) were collected
      using an extension line connected to a push-pull system. Birds were unrestrained
      and had free access to food and water. Red blood cells were recovered by
      centrifugation, reconstituted in saline solution, and returned to the donor bird
      through the VAP once every 90 min. Luteinizing hormone levels were subsequently
      measured in plasma by radioimmunoassay. With the exception of 1 hen that
      developed valvular endocarditis, no sign of disease or infection was observed
      throughout the study, and the VAP remained functional in all birds for at least 3
      mo. Thus, our results suggest that VAP are a safe, reliable, and less stressful
      technique for serial blood sampling and long-term studies. Radioimmunoassay
      results revealed that in old birds, circulating LH levels followed a pulsatile
      pattern, with pulse amplitudes ranging from 1.35 to 2.02 ng/mL and pulse
      frequencies ranging from 5 to 6 peaks per 6 h. Although not significant,
      amplitude of LH pulses in out-of-lay hens appeared to be lower than in laying
      hens.

PMID- 16977851
TI  - Effects of in ovo exposure to imazalil and atrazine on sexual differentiation in
      chick gonads.
AB  - We examined the effects of atrazine and imazalil, 2 commonly used pesticides, on
      sexual differentiation in chickens. Atrazine and imazalil were injected into
      fertile eggs on d 0. At hatching, sex genotype and phenotype were determined.
      Gonads were stereomicroscopically and histologically observed. In ovo exposure of
      atrazine (0.01 to 3 mg/egg) did not influence hatchability, whereas imazalil
      exposure (2 mg/egg) inhibited hatchability. The sex genotype matched the sex
      phenotype in controls, atrazine, and imazalil-exposed groups. In control females,
      the right gonad was regressed at hatching. Regression of the right gonad,
      however, was inhibited following atrazine and imazalil exposure. In atrazine
      exposed female chicks, the left gonads had normal ovary structures, and the
      remaining right gonads had ovary medulla-like structures. In imazalil-exposed
      females, some left gonads had an ovary medulla-like structure without the cortex
      as well as tubules, and the right gonad had testis-like structures. There was no
      change in male gonads at hatching following atrazine and imazalil exposure.
      Aromatase activity of the left gonad from female chicks was not changed by any
      concentration of atrazine exposure. These results suggest that atrazine and
      imazalil inhibit regression of the right gonad in female chicks, although it is
      not clear whether the remaining right gonad has aromatase activity. In ovo
      exposure to atrazine influences sexual differentiation of the ovary by different
      mechanisms from imazalil, possibly by the induction of aromatase in the right
      gonad, whereas it is confirmed that imazalil inhibits in vitro aromatase activity
      in the chick ovary. The results indicated that in ovo exposure to imazalil
      inhibits sexual differentiation of the ovary by inhibiting aromatase activity.

PMID- 16977852
TI  - Use of apparent transverse quantitative ultrasonography to assess skeletal
      integrity in layers.
AB  - Although there are several techniques currently available to assess skeletal
      integrity in live birds, few offer important features for application in a
      commercial setting, offering ease of use and moderate cost. Quantitative
      ultrasonography (QUS) is an established technique for diagnosis of osteoporosis
      in humans and horses that has potential application for layers. An OmniSense 700S
      quantitative ultrasonometer was evaluated for use with Single Comb White Leghorn
      hens. Humeral QUS values (m/s) were measured in a series of experiments using a
      total of 144 Shaver White hens. Significant correlations (P < 0.01) were observed
      among sequential QUS measurements taken on the same bird at 54, 60, and 66 wk of
      age. At the completion of the studies (66 wk of age), the left and right humeri
      were excised, cleaned, and rescanned. Postmortem QUS data from left and right
      humeri were related (R2 = 0.72, P < 0.0001), although future studies may need to
      consider both sides of the skeleton to account for asymmetry conditions.
      Ultrasound data collected from live hens at 66 wk of age correlated well with
      postmortem QUS data (R2 = 0.80, P < 0.0001). Quantitative ultrasonography did not
      correlate with humeral bone-breaking force measured postmortem. Bones from live
      hens, surrounded by tissue thicker than 4 mm, could not be read by the QUS probe.

PMID- 16977853
TI  - Influences of feeding conventional and semisynthetic diets and transport of
      broilers on weight gain, digestive tract mass, and plasma hormone and metabolite
      concentrations.
AB  - Two replicate experiments were done to investigate if special diets provided to
      broilers in their last phase of life could reduce the negative effects of feed
      withdrawal and transport without an increased content of the digestive tract. In
      each experiment, 240 broilers were used. The experiments consisted of 2
      interventions: the feed intervention and the transport intervention. The feed
      intervention took 72 h, in which broilers had full access to a conventional
      grower diet, a conventional grower diet with an increased carbohydrate level, a
      conventional grower diet with an increased fat level, a semisynthetic diet, or a
      semisynthetic diet with an increased carbohydrate level. The diets differed
      remarkably in carbohydrate content; carbohydrate content was approximately 67% in
      the semisynthetic diets and 42%, on average, in the conventional diets. Moreover,
      all of the carbohydrates in semisynthetic diets were highly soluble and
      digestible. The diets were compared with a feed withdrawal period of 24 h before
      transport. The transport intervention took 3 h; broilers were caught, crated,
      loaded, transported for 1.5 h, and had to wait in the crates for 1 h thereafter;
      or remained in the pens. After the transport intervention, blood samples were
      taken to determine plasma corticosterone, triiodothyronine, glucose, lactate,
      uric acid, nonesterified fatty acid, and triglyceride concentrations. Also,
      changes in live weight (LW) and digestive tract mass were assessed. The LW losses
      of broilers fed with semisynthetic diets after transport were 0.24% per hour less
      than of feed-withdrawn broilers. Moreover, intake of semisynthetic diets was
      approximately 200 g, whereas the intake of conventional diets was approximately
      300 g. Therefore, the digestive tract mass as a percentage of LW was lower for
      semisynthetic-fed broilers in comparison with conventional-fed broilers, which
      can lead to a lesser degree of contamination during evisceration. No increase of
      corticosterone was found due to transport in semisynthetic-fed broilers.
      Semisynthetic feed with high carbohydrate concentration could be a good
      alternative for the feed withdrawal period held before transportation to the
      processing plant.

PMID- 16977854
TI  - Preslaughter mortality in broiler chickens, turkeys, and spent hens under
      commercial slaughtering.
AB  - The incidence of dead on arrival (DOA) birds was surveyed over 33 broiler, 11
      turkey, and 19 spent hen abattoirs representing the majority (around 70%) of the
      Italian poultry slaughter plants. Data were recorded monthly during a 4-yr period
      (August 2001 to July 2005), considering a total of 1266 million chicken broilers,
      118 million turkeys, and 54 million spent hens, which represent 67.7, 84.0, and
      28.4% of the national production, respectively. The overall average incidence of
      DOA was found to be 0.35, 0.38, and 1.22% in broilers, turkeys, and spent hens,
      respectively. The season significantly (P < or = 0.01) influenced the mortality
      of all considered poultry categories, with higher incidence being observed during
      the summer (0.47, 0.52, and 1.62% for broilers, turkeys, and spent layers,
      respectively). The incidence of DOA broilers was found to be lower in small
      slaughter plants compared with medium and large slaughter plants (0.28 vs. 0.38
      and 0.35%, P < or = 0.01). The data obtained in this study might be used for
      establishing limit values of DOA as a welfare indicator during the preslaughter
      time of birds, including catching, loading, transportation, and lairage.

PMID- 16977855
TI  - Antimicrobial resistance in Salmonella and Escherichia coli isolated from
      commercial shell eggs.
AB  - The development of antimicrobial resistance in bacteria has become a global
      problem. Isolates of Salmonella and Escherichia coli recovered from shell egg
      samples, collected at 3 commercial plants, were analyzed for resistance to 16
      antimicrobial agents (n=990). Eggs were sampled by rinsing in a saline solution.
      Pooled samples were preenriched in buffered peptone water and then selectively
      isolated using standard broths and agars. Salmonella-positive isolates were
      serogrouped immunologically before being serotyped. Enterobacteriaceae were
      enumerated from individual samples using violet red bile glucose agar plates.
      Escherichia coli were identified biochemically from presumptive
      Enterobacteriaceae isolates. Salmonella and generic E. coli antimicrobial
      susceptibility testing was conducted using a semiautomated broth microdilution
      system. More resistance was observed in the Salmonella isolates (n=41) than in
      the E. coli isolates (n=194). Salmonella Typhimurium was the most prevalent
      (69.0%) serotype and demonstrated the greatest multiple resistance. Salmonella
      Kentucky, the least prevalent (5.0%) serotype recovered, was the most
      susceptible. Although 34.1% of the Salmonella serotypes were susceptible to all
      antimicrobial agents, 60.1% were resistant to 11 or more compounds. Many
      Salmonella isolates exhibited resistance to tetracycline (63.4%), nalidixic acid
      (63.4%), and streptomycin (61.0%). Most E. coli isolates (73.2%) were susceptible
      to all antimicrobial drugs. Many E. coli isolates exhibited resistance to
      tetracycline (29.9%), streptomycin (6.2%), and gentamicin (3.1%). Only 1% of the
      E. coli isolates were resistant to 4 antimicrobial agents. These data indicate
      that shell eggs can harbor resistant foodborne and commensal bacteria; among
      Salmonella isolates, resistance was serotype-dependent.

PMID- 16977856
TI  - Monitoring of eggshell breakage and eggshell strength in different production
      chains of consumption eggs.
AB  - We first tried to monitor the critical points for eggshell breakage in different
      logistic chains. Second, we examined whether there was a difference in eggshell
      strength among eggs produced in different housing systems. Finally, we developed
      a model to investigate the relation between eggshell strength and the likelihood
      of an egg cracking during handling and grading. Four logistic chains with
      different housing systems (battery cages, furnished cages, aviary, and free
      range), all housing Bovans Goldline chickens in their mid-lay (45 wk), were
      compared. In every chain, a randomized set of 1,500 eggs was sampled, and the
      strength was defined. At every critical point in every logistic chain, the eggs
      were reexamined for breakage. The classic and furnished cage systems showed the
      highest percentage of breakage directly at point of lay (6.73 and 10.72%),
      whereas the other systems showed lower breakage (1.94% in the aviary and 1.99% in
      the free-range system). Further, in the logistic chain, grading and packing of
      the eggs generated the second highest percentage of breakage (from 1.50 to
      2.65%). Breakage due to transportation ranged from 0.16 to 2.65%. There was a
      significant difference among the eggshell strength (shell stiffness and damping
      ratio) of eggs from chickens in different housing systems, showing eggs from
      chickens in the aviary system to be stronger than cage eggs (classic and
      furnished) and free-range eggs to be weaker than the other eggs. A significant
      correlation was found between eggshell strength and the likelihood of breakage in
      the production chains. In conclusion, it was first shown that, besides the
      laying, packing of the eggs is a critical point in the logistic chain of
      consumption eggs; second, the strength of the eggs in the different housing
      systems differed, and, finally, the eggshell stiffness and damping ratio of
      consumption eggs are an acceptable measure for rapid eggshell quality assessment
      and could provide a good predictive value for eggshell breakage in all types of
      table egg production chains.

PMID- 16977857
TI  - In vitro study of Salmonella enteritidis and Salmonella typhimurium definitive
      type 104: survival in egg albumen and penetration through the vitelline membrane.
AB  - Salmonella enteritidis and Salmonella typhimurium definitive type 104 (DT104)
      have been detected in the chicken oviduct, and their survival in egg albumen at
      the chicken body temperature of 42 degrees C may be important in oviductal and
      transovarian contamination of intact shell eggs. Eight S. enteritidis and 24 S.
      typhimurium DT104 strains were tested for their in vitro survival in egg albumen.
      The concentration of the organisms declined more rapidly when incubated at 42
      degrees C than at 37 degrees C and dropped to nondetectable levels within 96 h at
      the higher, but not at the lower, temperature. In another experiment, 3 S.
      enteritidis and 3 S. typhimurium DT104 strains were randomly selected, and
      dosages of 20 and 200 cells of each strain were inoculated onto the vitelline
      membranes of egg yolks, which were then submerged in the original albumen and
      incubated for 24 h at 42 degrees C. Under these conditions, the organisms
      survived in albumen but did not penetrate the vitelline membrane. However, in a
      similar experiment, penetration did occur when the specimens were incubated at 30
      degrees C for 72 h. The results suggest that low numbers of S. enteritidis and S.
      typhimurium DT104 can be expected to survive in egg albumen during the 24-h
      period of egg formation in the oviduct but would be unlikely to invade the
      yolk.before oviposition. However, depending on storage conditions following
      oviposition, S. enteritidis, as well as S. typhimurium DT104, could survive
      longer and may eventually invade the egg yolks.

PMID- 16977858
TI  - Laying performance of pearl gray guinea fowl hens as affected by caging density.
AB  - The caging density required for optimal egg production by various avian species
      and varieties is highly variable. Even so, little is known of the required cage
      density for optimum performance of the laying guinea fowl (Numida meleagris). The
      objective of this study was to assess the effect of varying cage densities on
      production performance of pearl gray guinea fowl laying hens. In 3 replicates,
      270 pearl gray guinea hens [28 wk of age (WOA)] were weighed individually and
      randomly assigned to laying cages at densities of 1, 2, and 3 birds/cage,
      equivalent to 1394, 697, and 465 cm2/bird, respectively. During the experiment,
      all birds received a 16-h lighting regimen and were fed the same diet, comprising
      2800 kcal of ME/kg of diet and 16% CP (28 to 59 WOA) and 2800 kcal of ME/kg of
      diet and 14% CP (60 to 76 WOA). Feed and water were provided for ad libitum
      consumption. Experimental birds were observed for feed consumption (FC), hen-day
      egg production (HDEP), egg weight, egg mass (EM), feed conversion ratio, internal
      egg quality, and shell thickness at the end of each 28-d lay period for 11
      consecutive periods. Mean FC and HDEP decreased significantly with increases in
      cage density, such that 1394 > 697 > 465 cm2/bird. Mean EM was also higher (P <
      0.05) for birds reared in cages at 1394 cm2/bird than those reared in cages at
      697 and 465 cm2/bird (24.8, 17.4, and 14 g/hen per d, respectively). Feed
      conversion, HDEP, and EM were negatively correlated with cage density (P < 0.05).
      Mean feed conversion ratio and percentage of mortality were also lower in birds
      reared in cages at 1394 cm2/bird than in other treatment groups. Therefore,
      laying guinea fowl hens exhibited superior performance when raised at a density
      of 1 bird/cage (1394 cm2/bird) than those reared at densities of 2 and 3
      birds/cage (697 and 465 cm2/bird, respectively).

PMID- 16977859
TI  - [Meningiomas with skull bone involvement].
AB  - One of factors responsible for meningioma recurrencies is tumorous involvement of
      calvarial and basal bone structures. Primary intraosseous meningiomas should be
      distinguished from secondary involvement in prevailing intracranial tumor and
      hyperostotic reactive changes. The paper is based on prospective study of 167
      patient operated on for intracranial meningioma. Based on clinical investigation,
      radiological and intraoperative data bone invasion was suspected in 20 patients
      and histologically confirmed in 17. In 14 patients bone involvement was
      secondary, meningothelial hamartoma was described in one patient and in 2 patient
      primary intraosseous meningioma was found. Prevalence of tumors to periorbital
      area and bone sutures is confirmed. Neuronavigation is used to optimise tumor
      resection and limit the risk for neurovascular structures. Results were good in
      87.5% of patients and poor in 12.5% of patients (extent of tumor and general
      condition). Discussion provides analysis of intraosseous meningiomas formation,
      pathological classification (Lang), causes of bone invasion and surgical
      possibilities. It is necessary to undeline the problems of intraosseous
      meningiomas both from the aspects of diagnosis and subsequent treatment.

PMID- 16977860
TI  - [Postintubation stenosis of the trachea--case reviews].
AB  - Stenoses of the respiratory tract are life threatening conditions of various
      origins. The authors give referrence on 21 patients operated for postintubation
      stenoses of their trachea at the IInd Surgical Clinic of the UPJS Medical
      Faculty, the Faculty Hospital of L. Pasteur in Kosice, from 01. 01. 1999 to 30.
      06. 2005. All patients had a tracheobronchoscopic examination and a CT
      examination completed prior to the procedure. Within 24 hours of their admission,
      9 patients were operated, 7 underwent resection procedures and 2 patients had
      Montgomery's T-cannula introduced. 12 patients had their procedures planned, and
      were operated later than 24 hours after their admission. 10 patients underwent
      resections of the trachea, 2 had Montgomery's T-cannula implanted. The
      postoperative course following the resection of the trachea was without
      complications in 14 patients, 1 patient experienced transitional oedema in the
      anastomosis and 2 patients suffered restenoses. In this patient group, no fatal
      case was recorded. The authors stress up multidisciplinary approach in the
      diagnostics and treatment of the postintubation stenoses of trachea. In cases of
      postintubation stenoses of trachea, resection of the trachea with primary
      anastomosis represents the most advantageous treatment approach for the patient.

PMID- 16977861
TI  - [Actinomycosis of the lungs mimicking a Pancoast tumor].
AB  - The authors present a case-review of a patient with a thoracic form of
      actinomycosis, simulating a "pancoastoid" lung tumor clinical picture-
      furthermore, confirmed by a false-positive cytological examination. The disorder
      was managed by enlarged lobectomy from the right lung, followed by postoperative
      antibiotic therapy, lege artis. The long-term outcome is very good.

PMID- 16977862
TI  - [Post-traumatic cerebral sodium and water wasting syndrome, CSWS--a case review].
AB  - The authors present a case-review of a posttraumatic syndrome with natrium ions
      and water wasting, resulting in hyponatraemia. The patient concerned was a
      polytraumatized female patient, with a gradual onset of her symptoms, starting
      from the day 15 following the trauma. A pharmacological treatment failed. The
      loss of water and ions was supplemented mainly via i.v. route. 54 days later, the
      patient had no signs of the syndrome and the substitution could be withdrawn.

PMID- 16977863
TI  - [Spontaneous pneumomediastinum].
AB  - Spontaneous pneumomediastinum is a presence of free air in the mediastinum
      without previous injury and without previously known lung disease. Spontaneous
      pneumomediastinum is infrequent and little known by physicians. Authors present a
      case report of three young men with spontaneous pneumomediastinum. There was no
      evident causation in two cases. In one case there was previous excessive sport
      activity. Main presenting symptoms were chest and neck pain, odynophagia,
      dysphonia, vomiting, and neck subcutaneous emphysema. Esophageal perforation was
      ruled out. All patients recovered spontaneously. Spontaneous pneumomediastinum is
      the benign disease. Its main importace is in differential diagnosis concerning
      especially esophageal perforation.

PMID- 16977864
TI  - [Hartmann's resection of the large intestine--a method still useful].
AB  - Hartmann's procedure is an operation indicated especially in emergency cases for
      left-sided colonic pathology where primary anastomosis is considered unsafe.
      METHODS: Retrospective study 95 patients who underwent Hartmann's procedure over
      a 5 year period in the Surgical Clinic of the University Hospital in Pilsen.
      RESULTS: 81 (85%) operations were emergency procedures. 45 (47%) operations were
      done for the malignant disease, the remaining 50 (53%) for benign disease (33 for
      complications of diverticular disease). Median age of patients was 69.4 years.
      The 30-day mortality rate was 16.8%. 37 patients had colostomy reversed, after a
      mean of 5.6 months with no mortality. CONCLUSIONS: Hartmann's procedure is a safe
      method. Our results are similar to results collected by foreign clinics.

PMID- 16977865
TI  - [Radiofrequency assisted liver resection in non-cirhotic liver. Initial clinical
      experience].
AB  - AIM OF THE STUDY: To evaluate the radiofrequency assisted liver resection using
      Habib sealer (RITA Medical System, Inc., Mountain View, CA). METHODS: The
      operation time, liver transection time, transfusion units used, and postoperative
      complications were recorded in a prospective way. RESULTS: 22 liver resections
      were performed between July 2005 and December 2005, 15 of them were done using
      radiofrequency technique. Twelve anatomical resections and three non-anatomical
      resections were performed in total. The mean operation time equalled 155 (120
      240) minutes. An average of 0.6 (0-4) transfusion units was used. In 13 of the 15
      operations, which represent 86% of the patients, no transfusions were used.
      Postoperatively, no major bleeding from the resection plane was noted and no
      biliary fistula was observed. CONCLUSIONS: Radiofrequncy assisted liver resection
      is a safe technique with the major benefit of minimal perioperative blood lost.

PMID- 16977866
TI  - Post-operative intraperitoneal adhesion prevention--the recent knowledge.
AB  - This article deals with the current knowledge on the possibilities of
      intraperitoneal adhesion prophylaxis in correlation with intraperitoneal
      interventions in abdominal surgery. The up-to-date experimental possibilities and
      other known methods are presented. These include: Intraperitoneal perfusion by
      certain special simple solutions--Dextran, Carboxymethycellulose, Crystalloid
      solutions, and Hyaluronidase. Intraperitoneal or other administration of certain
      drugs--Tetracyclines, Cephalosporins, Corticosteroids, Non-Steroidal Anti
      inflammatory drugs, Histamine agonists, Ca-channel blockers, Heparin, Citrates
      and Oxalates, Streptokinase, Urokinase, Plasminogen activators, and application
      of special synthetic or natural materials intraperitoneally--Surgicel, Interceed,
      Gore-Tex, Fibrin Glue, or various combinations of the above mentioned. Rats,
      rabbits, and mousses were used, first of all, as an animal model in presented
      experiments.

PMID- 16977867
TI  - [Endoscopic transgastric drainage of a pancreatic pseudocyst--a cause of late
      perforation of the intestine].
AB  - The authors present a case-review of a polymorbid patient, who underwent
      repetitive endoscopic transgastric drainage of the pancreatic pseudocyst in
      chronic pancreatitis. 3 months after the stents were released, the terminal ileus
      perforated. Ileocaecal resection was then completed. Further postoperative course
      was uncomplicated and the patient's current clinical condition is good.

PMID- 16977868
TI  - [Causes of recurrencies following procedures for varicose veins of the lower
      extremities].
AB  - AIM: The aim of the study is to analyze causative factors of recurrencies
      following varicose veins procedures, and to propose procedures aimed at reduction
      of the relapse rates. MATERIAL AND METHODOLOGY: During the period of 1993-2005,
      2034 extremities in 1756 patients were operated. 24% of the cases were
      reoperations, 85% of the operated were sclerotized pre- or post-operatively.
      Total anaesthesia was used in 1350 subjects, 406 patients underwent procedures
      under local anaesthesia. Complete crossectomy was completed, mostly including
      invagination stripping of the femoral part of the VSM. When necessary, the
      saphenopopliteal junction and perforators were resected. RESULTS: No deaths were
      recorded. The complication rate was 3.8%, all were managed without
      hospitalization and included the wounds healing complications. 91% of patients
      were discharged on the day of the procedure. Over 50% of patients were not out of
      work. 420 procedures were reoperations (24%). None or incomplete crossectomy was
      analyzed as the relaps cause in 65% of the cases. None or misconduct resection of
      the saphenopopliteal junction and perforators resulted in relapses in 35% of the
      cases. In all cases, it could be concluded, that badly managed, or not at all
      managed, reflux was the cause of the reoperations. Following completion or either
      primary operation or reoperation by our team, 404 operated were lost from our
      evidence, 1352 patients were followed up regulary. 16 patients (1.2%) were
      indicated for another surgical procedure, 14 of them were indicated for the
      saphenopopliteal junction incompetence and 2 for its reincompetence. No new
      reflux in the groin region was recorded. CONCLUSION: Badly managed, or not at all
      managed, saphenofemoral or saphenopopliteal reflux was the cause of significant
      recurrencies resulting in reoperations. Neoanginogenesis was not recorded and the
      authors refuse to accept it as a cause of the relapses of the varicose veins.
      Exact diagnosis, correct indication and sufficient radicality of the procedure
      prevent recurrencies of the disorder.

PMID- 16977869
TI  - [Bleeding from aortointestinal fistula].
AB  - INTRODUCTION: Aortointestinal fistula is a patological communication between the
      aorta and the gut. Two groups of these fistulas are described. The primary
      fistulas originated as complications of aneurysma of the abdominal aorta and the
      secondary fistulas as a consequence of reconstruction of the abdominal aorta or
      the iliac arteries. CASE REPORT: A case report of 69-year-old man operated for
      aneurysma of abdominal aorta with implanted aortal prosthesis is described. Four
      years after the surgery he complained for bleeding into the digestive tract. The
      only the small lesions of the stomach were found during endoscopy. A strong
      attack of bleeding which followed later recquired a laparotomy where aortoileal
      fistula located in distal anastomosis between the aorta and the prosthesis was
      found. Despite of the intensive care patient died because of haemorhagic shock.
      DISCUSSION AND CONCLUSION: Based on literature review and also based on the own
      experience author concludes that every patient with intraabodominal pulsating
      resistance, or with known diagnosis of the abdominal aorta aneurysma, or with
      aortal prosthesis who presents with features of the sepsis or bleeding into the
      digestive tract is suspicious from presence of aortointestinal fistula. The
      patient should be immediately examined by spiral CT with contrast and operated.

PMID- 16977870
TI  - [Prophylactic antibiotics in plastic surgery].
AB  - There is no consensus on the use of prophylactic antibiotics in plastic surgery
      to prevent postoperative infection. This study was performed to investigate
      whether the use of prophylactic antibiotics has an effect on postoperative
      infection rate. A total of 500 patients were classified into 3 groups based on
      their diagnosis. Approximately half of the cases received amoxicilin/clavulanate
      combination the other half had no antibiotics. Wound infection was observed in
      the post operative period. According to our clinical findings, antibiotic
      prophylaxis is not necessary in plastic surgery in all patients. We did not find
      significant difference between the antibiotic prophylaxis and placebo group.

PMID- 16977871
TI  - [Venous thrombosis prophylaxis in surgery--beginnings, contemporary state, ACCP
      consensus, future prospects].
AB  - Presentation and analysis basis questions and changes of thromboembolic disease
      prophylaxis in the surgical specialities from point of view the developments in
      last 30 years. Demonstration of the basic and modren methods of deep venous
      thrombosis prophylaxis. Recommendation of the 7th conference ACCP-CHEST 2004.

PMID- 16977872
TI  - [Surgical treatment method of calcaneal intraarticular fractures].
AB  - Open repositioning and internal fixation of intraarticular calcaneal fractures
      has become a standard surgical method, however, concerns over its feared
      complications, including, in particular, secondary wound healing followed by
      osteomyelitis, continue fo be discussed. The aim of this study is to inform the
      surgical public about the surgical method. From February 2004 to September 2005,
      26 intraarticular calcaneal fractures in 22 patients were operated using open
      repositioning and internal cast fixation. In four cases, the fracture was
      bilateral. The patients were indicated for the procedure based on the Sanders CT
      classification. The procedure included extensive L-shaped lateral approach
      (Seattle), anaemization, minimization of soft tissue disruption, and was followed
      by spongioplasty. In isolated dislocated sustentacular fractures, osteosynthesis
      through a medial approach was completed, using screws. Post-operatively, the
      extremity was not fixated and early rehabilitation was initiated. In majority of
      the operated patients, the skin cover healed per primam. In 3 patients, the wound
      healed per secundam intentionem. Complete fracture healing was x-ray confirmed in
      all patients. No signs of the osteosynthetic material release or of pronounced
      signs of subtalar arthrosis or of a foot arch collapse were present. No deep
      defects or other serious postoperative complications were recorded. The follow-up
      period lasted for 6-22 months and goes on. The patients followed for over a year
      period have no symptoms, they fully wightbear the operated extremity and they
      have returned to their original professions. Open repositioning and internal
      stable cast fixation is recommended as a standard treatment method in these
      fractures.

PMID- 16977873
TI  - [The dynamics of personality changes in combatants of local wars and armed
      conflicts].
AB  - 326 combatants have been examined using clinical-and-experimental psychological
      methods in outpatient and hospital conditions in order to reveal personality
      changes as a result of transient combat stress. The dynamics of these changes in
      pre- and post-combat periods has been described. Some personality peculiarities
      acquired in combat conditions aggravated combatants' rehabilitation to the peace
      life, which should be taken into consideration during rehabilitation. The
      medicopsychological correction of the combatants with personality accentuation
      must be made in view of the variety of these disorders.

PMID- 16977874
TI  - [Organization of municipal medical-and-social rehabilitation of the invalids of
      able-bodied age-veterans of armed conflicts].
AB  - A territorial model of the organization of medical-and-social rehabilitation of
      labor-liable-age invalids was studied basing on the results of the experiment
      which enabled to test in practice the system of rehabilitation, ensuring step-by
      step persistent successive complex rehabilitation process with an individual
      approach to each invalid according to his or her health, personality, labor
      ability, social environment. The efficacy of this treatment was higher than
      executing separate medical and professional rehabilitation of invalids.

PMID- 16977875
TI  - [Some problems of regulation and improvement of activity of the military drug
      stores].

PMID- 16977876
TI  - [Resection of the liver in focal lesions].

PMID- 16977877
TI  - [Choice of the surgery method in adenoma of the prostate gland].

PMID- 16977878
TI  - [Endoscopy observation of patients with conducted eradication therapy of
      Helicobacter pylori in gastric and duodenal ulcer].

PMID- 16977879
TI  - [Non-alcoholic steatohepatitis].

PMID- 16977880
TI  - [The new domestic immunoglobulin G gabriglobin in complex therapy of
      immunodeficiency states and infectious pathology].

PMID- 16977881
TI  - [The role of local factors in the development of acute and chronic
      rhinosinusitis].

PMID- 16977882
TI  - [Peculiarities of tactics in the treatment of chronic pain syndrome in women].

PMID- 16977883
TI  - [Hemorrhagic fever with the renal syndrome: modern aspects of epidemiology and
      prophylaxis].
AB  - Hemorrhagic fever with the renal syndrome (HFRS) is a typical natural-and-focal
      virus infection having military-and-epidemiological importance for Armed Forces
      of most countries. Severe forms of this infection are typical for the Far East of
      Russia, countries of South-East Asia and especially for the American continent.
      The lethality from HFRS amounts to 15-50%. The main natural carriers and keepers
      of HFRS stimulus are various mouse-type rodents. In Russia besides well-studied
      natural focuses on the Far East, Siberia, Ural, Povolge other active HFRS focuses
      were determined not long ago (Moscow, Orel, Lipetsk, Tula and Voronezh regions,
      the territory of Big Sochi). A man is infected by an aerosol, forming during
      drying up of rodents' urine, feces, saliva containing HFRS virus. Vaccinal
      prevention of HFRS in Russia hasn't yet been worked out. Ribavirin is the most
      effective in the treatment for HFRS. The means of prevention of population and
      servicemen must exclude their contact with rodents both in natural conditions and
      in populated areas.

PMID- 16977884
TI  - [Radio-ecological and medical-and-sanitary consequences of the Chernobyl
      disaster].

PMID- 16977886
TI  - [Concept of professional health and perspectives of practice of military aviation
      medicine].

PMID- 16977885
TI  - [The influence of aviation noise on the hearing organ in engineering-and
      technical staff of Air Forces].

PMID- 16977887
TI  - [Portable domestic surgical equipment].

PMID- 16977888
TI  - [Outstanding organizer and historian of military medicine (to 100-year birthday
      anniversary of S.A.Semeka)].

PMID- 16977890
TI  - Pharmaceutical sales reps: value beyond samples.

PMID- 16977891
TI  - Alcohol abuse among women.

PMID- 16977892
TI  - Hypertension, hypokalemia and edema in a patient with cough.

PMID- 16977893
TI  - Central venous catheterization.

PMID- 16977894
TI  - Patient information. Protect yourself from the sun.

PMID- 16977895
TI  - Effective management of pressure ulcers. A review of proven strategies.

PMID- 16977896
TI  - Preventing amputation in older adults with diabetes.

PMID- 16977897
TI  - Treating dog and cat bites.

PMID- 16977898
TI  - Peripheral arterial disease. Simple screening tool could diagnose more cases.

PMID- 16977899
TI  - Systemic lupus erythematosus. An overview.

PMID- 16977900
TI  - Heart failure: lost in transition.

PMID- 16977901
TI  - Bartter's syndrome.

PMID- 16977903
TI  - Depression in hepatitis C patients. What is the link?

PMID- 16977902
TI  - Vitamin B12 deficiency.

PMID- 16977904
TI  - Negotiating benefits. Salary isn't your only concern.

PMID- 16977905
TI  - Billing is your responsibility.

PMID- 16977906
TI  - How big is the health promotion market? Small but getting big, with Medicare
      leading the way.

PMID- 16977907
TI  - Physical activity of adults with mental retardation: review and research needs.
AB  - OBJECTIVE: To characterize physical activity levels of adults with mental
      retardation and identify limitations in published research. DATA SOURCES: Key
      word searches for "mental retardation," "intellectual disability," "learning
      disability," or "developmental disability" combined with "physical activity" or
      "habitual exercise" identified articles from MEDLINE, Academic Search Elite,
      Psych Articles, Health Source, and SPORT Discus. This produced a total of 801
      citations. STUDY INCLUSION AND EXCLUSION CRITERIA: Published English-language
      literature that quantitatively measured physical activity levels of adults with
      mental retardation was included in this review. Fourteen articles met this
      criterion. DATA EXTRACTION: Characteristics of participants, study design,
      outcome measures, methods of analyses, and findings in terms of percentages, step
      counts, and accelerometer output were extracted. DATA SYNTHESIS: Data were
      synthesized to identify the percentage of adults with mental retardation who met
      published health-related physical activity criteria and compare them with adults
      without mental retardation and to examine study limitations. RESULTS: The studies
      with the greatest rigor indicate that one-third of adults or fewer with mental
      retardation were sufficiently active to achieve health benefits. However, data
      are insufficient to determine whether adults with mental retardation are less
      active than the general community. CONCLUSIONS: Future research would be enhanced
      by including appropriately powered representative samples, by including
      comparison groups, by validating physical activity questionnaires, and by
      determining the accuracy of proxy respondents.

PMID- 16977908
TI  - Psychosocial factors associated with young elementary school children's
      intentions to consume legumes: a test of the theory of reasoned action.
AB  - OBJECTIVE: The purpose of this study was to test the utility of the Theory of
      Reasoned Action (TRA) in explaining young elementary school children's intention
      to consume legumes. METHODS: A survey was conducted with children in an urban,
      multicultural community in Massachusetts. A total of 336 children participated.
      Logistic regression analysis was used to assess the strength of the relationship
      between attitude and subjective norm and intention. RESULTS: Although attitude
      was significantly associated with intention, the pseudo-R2 for the regression
      model that included only the TRA constructs was extremely low (.01). Adding
      demographic factors and preference improved the model's predictive ability, but
      attitude was no longer significant. CONCLUSION: The results of this study do not
      provide support for the predictive utility of the TRA with young elementary
      school children for this behavior, when demographic factors are accounted for.
      Hedonic factors, rather than reasoned judgments, may help drive children's
      intentions.

PMID- 16977909
TI  - Factors associated with smoking cessation counseling at clinical encounters: the
      Behavioral Risk Factor Surveillance System (BRFSS) 2000.
AB  - PURPOSE: Characterize factors associated with smoking-cessation counseling in
      clinical encounters. DESIGN: Cross-sectional analysis of Behavioral Risk Factor
      Surveillance System (BRFSS) 2000 data. SETTING: U.S. households. SUBJECTS: 10,582
      smokers (aged > or = 18 years) reporting one or more clinical encounters during
      the prior year. MEASURES: Multivariate-adjusted odds ratios (OR) and 95%
      confidence intervals (CI) for quit advice associated with respondent and
      encounter variables. RESULTS: Almost 55% of respondents were advised to quit
      smoking. Young men were advised to quit least often. Increasing age (18-24, 25
      39, 40-64, > or = 65 years) was associated with increasing odds of receiving quit
      advice (OR = 1.33, CI 1.10-1.61) for men. Other positive associations with quit
      advice included patient education, BMI, diagnosis of asthma, and private health
      insurance. Patients seeing physicians had greater odds of being advised to quit
      smoking (OR = 3.29, CI 2.13-5.06) than those seeing dentists. There was a 4% to
      23% chance of receiving quit advice at any given nondental clinical encounter;
      the odds of such counseling did not rise significantly with the number of visits.
      CONCLUSION: Smoking cessation counseling may be provided preferentially on the
      basis of patient demographics, and often is not provided at all. In a given year,
      just over half of smoking patients are advised to quit, and such counseling is
      provided at less than a quarter of clinical encounters.

PMID- 16977910
TI  - Perceived environments as physical activity correlates and moderators of
      intervention in five studies.
AB  - PURPOSE: Few studies have explored how relationships of perceived environment and
      physical activity vary across different activity domains and populations. This
      question was explored in five physical activity intervention trials funded by the
      National Institutes of Health Behavior Change Consortium. DESIGN: Observational.
      SETTINGS: San Francisco peninsula, California (N = 94); Eugene, Oregon (N = 122);
      Atlanta, Georgia (N = 256); Kingston, Rhode Island (N = 109); Memphis, Tennessee
      (N = 64). SUBJECTS: Ethnically diverse community adults ages 18 to 85 years.
      MEASURES: The Neighborhood Environment Walkability Scale and CHAMPS physical
      activity questionnaire. Response rate among those invited to complete these
      measures was 90%. RESULTS: Cross-sectional pooled signal detection analysis
      indicated that people who reported living in neighborhoods with more attractive
      scenery and ease of walking were more likely to meet national physical activity
      recommendations (67%) compared with those without these neighborhood attributes
      (36%; chi2 = 13.04, p = .0003). Within-site multiple regression identified two
      additional variables--seeing others when walking and encountering loose dogs that
      make it difficult to walk--as correlates across multiple sites and activity
      domains (i.e., minutes of weekly moderate or more vigorous activity, walking for
      errands, walking leisurely) (incremental R2 = 2.0-7.5; p < .05). Analyses of
      covariance suggested that traffic safety might be particularly important in
      facilitating or impeding physical activity in response to a formal intervention
      (for traffic-arm assignment interactions, F = 3.8-7.0, p < or = .05).
      CONCLUSIONS: Relationships between perceived environments and physical activity
      may differ depending upon population groups and activity domains and merit
      investigation by using stronger prospective designs.

PMID- 16977911
TI  - Shelter environment and placement in community affects lifestyle factors among
      homeless families in Minnesota.
AB  - PURPOSE: To investigate the impact of the shelter environment and surrounding
      community on lifestyle factors influencing the health of homeless families.
      DESIGN AND SETTING: Seven focus groups were conducted at two homeless shelters
      serving families in Minneapolis, Minnesota. Food resources and food prices at
      convenience stores were recorded within a five-block radius of shelters.
      SUBJECTS: Low-income parents of children aged 3-12 years (n = 53). MEASURES:
      Focus groups were transcribed verbatim, evaluated for common themes, coded, and
      reevaluated for consistency. Food resources were mapped via GIS software, and
      recorded food prices were compared to available TFP market basket prices.
      ANALYSIS RESULTS: The shelter environment and surrounding community influenced
      lifestyle factors related to health, including food access and availability,
      exercise behaviors, job access, and day care issues. Participants commented that
      location of grocery stores, inflated prices, and poor food quality and variety
      limited their families' food choice and access. Walking was the main form of
      exercise and served as a means of transportation. Finding employment, housing,
      and affordable day care caused high levels of stress because of inadequate social
      support and government subsidies. CONCLUSIONS: Several strategies should be
      considered to modify environments affecting lifestyle factors among homeless
      families, including greater affordability and access of food, reevaluation of
      food stamp allotments, alterations in urban planning designs, and increased
      access to affordable day care.

PMID- 16977912
TI  - Evaluation of a community-based health promotion program for the elderly: lessons
      from Seniors CAN.
AB  - PURPOSE: To evaluate the effects of a community-based educational program
      designed to promote health by enhancing older adults' mastery while decreasing
      loneliness and stress. METHODS: Between 1999 and 2004, 339 older adults who
      participated in Seniors CAN completed standardized assessments of mastery,
      loneliness, and stress, prior to and upon completion of the 4-month intervention.
      Participants'scores were compared using paired t-tests to measure changes from
      preintervention to postintervention. Change scores were then subjected to three
      way ANOVA to assess the relative effectiveness based upon participants'
      sociodemographic characteristics. RESULTS: Participants demonstrated significant
      improvements from preintervention to postintervention for mastery, loneliness,
      and stress. Additional analysis revealed that improvement in loneliness was
      significantly greater among low-income ethnic minorities and minorities with a
      high level of formal education, p < .05. CONCLUSION: The 16-week intervention
      resulted in significant improvements in constructs associated with better health
      and a higher quality of life for independent-living older adults. These findings
      suggest that a community-based educational intervention can be an effective
      strategy to reduce risk and promote the health and independence of older adults.

PMID- 16977913
TI  - Both obesity and lack of physical activity are associated with a less favorable
      health-related quality of life in Hong Kong Chinese.
AB  - PURPOSE: To investigate the relationships among obesity, physical activity and
      quality of life (QOL) in Hong Kong Chinese adults. METHODS: A cross-sectional
      study involving 876 subjects (32.9% men and 67.1% women, mean age: 34.8 +/- 7.9
      years) from a nonmanual working population. The Medical Outcome Study Short Form
      36 (SF-36, Chinese version) was used for health-related QOL. Level of physical
      activity was assessed with self-reported questionnaire. Obesity was defined as
      body mass index > or = 25 kg/m2. RESULTS: 31% of men and 9% of women were obese
      (overall 16.0%). Obese subjects had lower scores on some of the SF-36 subscales.
      As the level of physical activity decreased, mean scores on most SF-36 subscales
      also progressively decreased. Obese women who had no regular physical activity
      had lower scores on some QOL subscales than obese women who had some regular
      physical activity. DISCUSSION: Among this Hong Kong Chinese sample, both obesity
      and lack of physical activity are associated with lower scores on QOL.

PMID- 16977914
TI  - Metabolic syndrome and worksite health promotion.
AB  - Metabolic Syndrome represents a relatively new clinical condition whose
      individual risk parameters have been associated with a variety of additional or
      excess costs for working populations. This article reviews much of the current
      clinical findings on this condition and provides suggestions for employers. The
      worksite represents one of the most promising settings for early detection and
      follow-up interventions. The most technically promising response from those
      responsible for employee health management is not clear at the present time.

PMID- 16977915
TI  - U.S. health insurers try to cash in on the growth of offshore surgery
      alternatives.

PMID- 16977916
TI  - SecureHorizons out to gobble up the Medicare advantage market.

PMID- 16977917
TI  - Making peritoneal dialysis and home hemodialysis more economically viable.

PMID- 16977918
TI  - New HRSA funding for donor programs?

PMID- 16977919
TI  - Diabetes: one part of the cardiovascular problem post-transplant.

PMID- 16977920
TI  - Diabetes control and education in transplant care improves outcomes.
AB  - Diabetes mellitus in any stage of the transplant process increases risks
      exponentially. Twice as many kidney recipients with pre-existing DM die with a
      functioning graft. Diabetes care is particularly challenging in the hospital
      environment, but frequently minimized. Since diabetes control makes such
      significant differences in patient outcomes, the American Diabetes Association
      and the American Association of Clinical Endocrinologists joined forces and
      published a position statement summarizing the preponderance of evidence
      supporting early detection and aggressive treatment of diabetes in the hospital
      setting. In the outpatient arena, a study at Stanford Medical Center demonstrated
      that a program of diabetes education reduced re-admissions related to diabetes
      from 93% to 7%. Rather than taking on endocrine responsibilities, nephrologists
      might shift that burden to a diabetes care team for education, treatment
      recommendations, and improved clinical profiles. Patients will benefit from a
      higher standard of renal and diabetes care.

PMID- 16977921
TI  - Laparoscopic live donor nephrectomy: evolution and current practice.

PMID- 16977922
TI  - Regulatory change for organ procurement organizations: certifying the success of
      transplantation in America.
AB  - In June 2006, the Centers for Medicare & Medicaid Services released the final
      rule for the conditions of participation for organ procurement organizations in
      the United States. The new guidelines change the way OPOs are measured, shifting
      from a population-based set of performance measures to a system that is based on
      eligible donors and conversion rates. In addition to the change in measurement
      philosophy, CMS has included statements, regarding organizational structure,
      staffing, and research as standard measures for OPOs. The change from solely
      donation and transplantation measures is significant for the community, and will
      result in changes in the way OPOs structure their organizations and governing and
      clinical boards.

PMID- 16977923
TI  - What if...? Helping to prepare individuals to become a living kidney donor.

PMID- 16977924
TI  - Are your patients ready? Empowering patients to create their best possible post
      transplant experience.

PMID- 16977925
TI  - Revamped websites offer more support to the transplant community.

PMID- 16977926
TI  - The emotional side of kidney transplant.

PMID- 16977927
TI  - A systematic approach to transplant education.

PMID- 16977928
TI  - Kidney transplant: an emotional issue.

PMID- 16977929
TI  - Choosing transplant.

PMID- 16977930
TI  - Transplant recipients.

PMID- 16977931
TI  - Organizing an expo: a patient event of a different kind.

PMID- 16977932
TI  - Understanding your personal competitive environment, part I.

PMID- 16977933
TI  - Facial profiling.

PMID- 16977934
TI  - Need a reason for selecting appropriate welding PPE?

PMID- 16977935
TI  - Flexible welding protection.

PMID- 16977936
TI  - As simple as 1, 2, 3.

PMID- 16977937
TI  - Glaring issues of a successful program.

PMID- 16977938
TI  - Protection: make sure their eyes have it.

PMID- 16977939
TI  - E pluribus unum.

PMID- 16977940
TI  - New and improved responder ensembles.

PMID- 16977941
TI  - A most valuable proposition.

PMID- 16977942
TI  - The missing link...is much more than just safety.

PMID- 16977943
TI  - Tangibly rewarding.

PMID- 16977944
TI  - Chemical database solves Hanford puzzle.

PMID- 16977945
TI  - How accurate is your monitor?

PMID- 16977946
TI  - Recording gas exposure with today's gas monitors.

PMID- 16977947
TI  - Imparting a new message.

PMID- 16977948
TI  - Socket grafting for optimal dental implant placement.

PMID- 16977949
TI  - The rise of the dental phoenix.

PMID- 16977950
TI  - Ethics in South African dentistry 2006.

PMID- 16977952
TI  - Accuracy of the Raypex-4 and Propex apex locators in detecting horizontal and
      vertical root fractures: an in vitro study.
AB  - Unforeseen root fractures during endodontic therapy are often difficult to
      diagnose and treat. Apex locators have been shown to be accurate in measuring the
      working lengths of root canals, and it was postulated whether they could also be
      used to determine the position of root fractures. This study was undertaken to
      assess the accuracy of two different apex locators in determining the position of
      fractures. One hundred single rooted teeth were randomly divided into two groups.
      One group had simulated horizontal fractures cut into them and the other group
      had vertical fractures. All fractures were detected in both groups using both a
      Propex (third generation) and a Raypex-4 (fourth generation) apex locator. The
      actual lengths of the fractures were then measured under 2.5 times magnification,
      and the results subjected to statistical analysis. Both locators produced similar
      results and were found to be very accurate, with measurements that correlated
      closely to the actual lengths. Clinically, treatment options for root fractures
      vary depending on their location. Thus apex locators may be a valuable aid in not
      only determining the presence of a root fracture, but also its exact location,
      which will help the clinician decide on the most appropriate management.

PMID- 16977953
TI  - Self-etching bonding systems: in-vitro micro-leakage evaluation.
AB  - The purpose of this in vitro study was to compare dentine and enamel micro
      leakage values of six self-etching bonding agents to that of a total etch dentine
      bonding agent (used as a control). Products evaluated were Scotchbond
      Multipurpose Plus (3M/ESPE), Xeno III (Dentsply), Clearfil SE Bond (Kuraray), ABF
      (Kuraray), Optibond Solo Self-Etch (Kerr), OneCoatSE Bond (Coltene Whaledent),
      and iBond (Heraeus-Kulzer). Using a medium sized Cerana bur (Nordiska Dental) a
      standard, cylindrical preparation was made at the cemento-enamel junction (CEJ)
      of human third molars. The teeth were randomly divided into 7 groups of ten teeth
      each. The bonding agents were applied and light cured strictly according to the
      manufacturer's instructions and the cavities then filled in two increments, using
      Z100 composite (3M/ESPE). The restored teeth were imbedded in acrylic resin and
      thermocycled between 5 degrees - 60 degrees C (+/- 2 degrees C) for 250 cycles
      with a dwell time of 20 seconds. All seven groups were then placed in a 5% basic
      Fuchsin solution for 12 hours at 37 degrees C. The embedded teeth were removed
      from the basic Fuchsin, rinsed well, imbedded in acrylic and cut longitudinally
      through the centre of each restoration using an Accutom-2 cutting machine. Each
      tooth was then evaluated at the occlusal enamel margin and at the cervical
      dentine margin for micro-leakage using a light microscope at 50x magnification.
      The data obtained was analysed using the Kruskal-Wallis test, with Fisher's least
      significant difference method used for comparison of specific groups (p<0.05).
      When compared to the control (Scotchbond Multipurpose Plus), results for
      microleakage at the occlusal enamel margins as well as the cervical dentine
      margins indicated that only SE Bond and ABF (Protect Bond) showed values as low
      as the control. It can be concluded that, as far as micro-leakage is concerned,
      Clearfil SE Bond and ABF (Protect Bond) self-etching bonding agents could be
      clinically acceptable alternatives to the clinically proven Scotch-bond
      Multipurpose. The other products showed more microleakage.

PMID- 16977954
TI  - Inflammatory dentigerous cyst in a 3 year old South African black male: A case
      report.
AB  - We present here a case of a dentigerous cyst in the anterior maxilla of a 3 year
      old male. There was associated cortical expansion and facial asymmetry. These
      cysts are rare at this age and in addition are less common in the maxilla.
      Management consisted of enucleation under general anaesthetic including removal
      of the unerupted 11. This report attempts to highlight the importance of prompt
      diagnosis and referral of children with dentigerous cysts.

PMID- 16977955
TI  - Updates on local anaesthetics.

PMID- 16977956
TI  - A review of gagging problems in dentistry: 2. Clinical assessment and management.
AB  - A pronounced gag reflex can be a severe limitation to a patient's ability to
      accept dental care and for a clinician's ability to provide it. It can compromise
      all aspects of dentistry from diagnostic procedures to active treatment and can
      be distressing for all concerned. Many 'management' techniques have been
      described. This paper describes the different categories of treatment used to
      manage people with pronounced gag reflexes.

PMID- 16977957
TI  - Off the record--no defence!

PMID- 16977959
TI  - Retrievability of the implant superstructure (part 2).

PMID- 16977958
TI  - General practitioner's pathology case 6.

PMID- 16977960
TI  - Sedation corner 11. Fluoxetine.

PMID- 16977961
TI  - General practitioner's radiology case 43.

PMID- 16977962
TI  - [Thrombotic microangiopathy in adults].
AB  - Thrombotic microangiopathic hemolytic anemias include thrombotic thrombocytopenic
      purpura (TTP), hemolytic uremic syndrome (HUS) and pregnancy associated
      thrombotic microangiopathy (TMA). Eight adult patients (four males and four
      females) with TMA who were treated between 2003 and 2004 at the Hospital Italiano
      de Buenos Aires were reviewed. The average age was 40. Clinical diagnosis of TMA
      was made on admission in four patients. During their stay in hospital, 4 patients
      developed HUS characteristics, three as TTP and one presented pregnancy
      associated TMA. All of them revealed thrombocytopenia and microangiophatic
      hemolytic anemia. Renal impairment was the third most frequent characteristic at
      presentation. The patients with TTP revealed the most severe condition. All
      patients received daily plasma exchange. Immunosuppressants were also used. Four
      patients recovered completely, 2 passed away, one remains with renal impairment
      and requires hemodialysis, and a colectomy was performed on one of them. The TMA
      syndromes are occlusive disorders associated to platelet microvascular thrombi.
      Systemic and renal circulations are primarily affected. TTP/HUS might represent
      an overlapping spectrum of idiopathic or secondary disease. Prompt recognition
      and treatment are vital, because high mortality occurs due to these disorders.
      Among the differential diagnosis of TMA we can refer to sepsis, neoplasms,
      systemic vasculitis, eclampsia and others. The mainstay treatments are daily
      plasma exchange and infusion with fresh frozen plasma. Improving the management
      of these diseases is required considering their high morbidity and mortality.

PMID- 16977963
TI  - Medium and long-term outcome of growth hormone therapy in growth hormone
      deficient adults.
AB  - We evaluated long-term replacement therapy outcomes in various subsets of
      patients with adult growth hormone (GH) deficiency (AGHD) as well as the
      patients' susceptibility to adverse events. Fifty-nine patients with AGHD were
      evaluated, 27 with childhood onset (CO) (18-44 years old, 12 females) and 32 with
      adult onset (AO) (27-70 years, 18 females). A significant improvement in HDL
      cholesterol was observed in AGHD-AO males (basal: 41.3 +/- 12.9 mg/dl,
      intratreatment: 47.5 +/- 13.2 mg/dl, p = 0.009). However, individual analyses
      showed that total cholesterol decreased below 240 mg/dl in 33% of AGHD-CO
      patients and in 50% of AGHD-AO patients, and below 200 mg/dl in 67% of AGHD-CO
      patients and in 29% of AGHD-AO patients; in the AGHD-AO group, normalization of
      LDL-cholesterol (< or = 160 mg/dl) and triglycerides (< or = 200 mg/dl) was found
      in 100% and 50% of patients, respectively; the total cholesterol/HDL ratio
      decreased below 4.5 in 20% of AGHD-CO patients and in 25% of AGHD-AO patients.
      The cardiological evaluation showed a significant intra- and interindividual
      heterogeneity, but cardiac mass improved in patients with a baseline cardiac mass
      index below 60 g/m2. Markers of bone apposition increased significantly, while
      bone resorption markers were found to remain unchanged during treatment. A
      correlation was found between increased bone mineral content and lean body mass
      (p = 0.0009). Susceptibility to adverse events was not found to be dependent on
      gender or on the time of onset of the deficiency. Our findings would appear to
      confirm that a more severe metabolic impairment is correlated with a better
      therapeutic outcome.

PMID- 16977964
TI  - [Chlamydia trachomatis and papillomavirus infection in women with
      cytohistological abnormalities in uterine cervix].
AB  - The presence of Chlamydia trachomatis and human papillomavirus (HPV) was
      evaluated by PCR technique in 189 sexually active women, between 15 and 58 years
      old, with cytological abnormalities in their uterine cervical epithelium and
      belonging to a region of Argentina with high incidence of cervical cancer. Risk
      factors in relation to chlamydial infection were also analyzed. Total prevalence
      for C. trachomatis infection was 24.9%, but there was a significant difference
      between prevalence in low socio-economical level (32.9%) and high or medium socio
      economical level (17.7%). Total prevalence for DNA of HPV was 52.9%, but women
      infected with C. trachomatis showed a higher risk for viral infection than non
      infected ones (OR = 2.27 / CI 95% = 1.10-4.73), with statistical significant
      difference (p = 0.016).

PMID- 16977965
TI  - [Cutaneous B cell processes with nodular pattern].
AB  - Cutaneous lymphomas are low grade malignant neoplasms with favourable prognosis.
      Those related to the germinal centre with nodular pattern may be: follicular
      lymphomas (LFC) or extranodal marginal zone B-cell lymphomas (LMC). They are
      difficult to tell apart, and from reactive processes like cutaneous follicular
      hyperplasia and cutis immunocytomas. The objective of this study was to check the
      incidence and the value of both histology and immunohistochemistry in
      differential diagnosis. Fifty six patients with cutaneous lymphomas were selected
      within the period 1995-2004. The biopsies were studied with hematoxilin eosin and
      immunohistochemistry. Thirty two out of the fifty six cutaneous lymphoid
      infiltrates were of T origin (57.1%) and twenty four of B origin (42.8%), ten out
      of this last figure (17.7%) were lymphoid processes with nodular pattern Four
      LFC, three LMC and three HLC were diagnosed. Convergent follicles with scarce
      mantle and germinal centres with monomorph celullarity were observed in the LFC.
      Among the LMC, follicles with prominent mantle and nests of monocitoid cells in
      the mantle, interfollicular zone and in the germinal centers observed. In the HLC
      macrophages with detritus were found in the germinal centers. LFC showed: CD20
      (+), CD 10 (+), bcl-2 (+) or (-), and bcl-6 (+) in the follicle and in the
      interfollicular area. LMC showed: CD 20 (+), bcl-2 (-), CD 10 (+/-), and bcl-6
      (+) in the follicle, and bcl-2 (+), CD10 (-/+) and bcl-6 (-) in the
      interfollicular area. The HLC results were: bcl-2 (-), bcl-6 (+) and CD 10 (-) in
      the follicle and bcl-2 (+), bcl-6 (-) and CD 10 (-) in the interfollicular zone.
      We conclude that lymphoid B cell processes with nodular pattern are unusual.
      Histology and immunohistochemistry proved to be useful in the differential
      diagnosis of these lymphomas, and for differentiating these from lymphoid
      hyperplasias or non tumoral hyperplasias.

PMID- 16977966
TI  - [Bronchioalveolar carcinoma: five year survival].
AB  - The epidemiology and prognosis of bronchioalveolar carcinoma (BAC) is different
      from adenocarcinoma. We studied 28 patients who underwent surgical resection and
      in whom a final histologic diagnosis of bronchioalveolar carcinoma was made.
      Sixty one percent of patients were asymptomatic at the time of diagnosis. The
      most usual radiological presentations were pulmonary nodule (11), pulmonary mass
      (6) and diffuse infiltrate (6). Nine patients (9/25) were never smokers.
      Bronchoscopy provided the diagnosis only in 4/26 patients. Patients were
      classified as stage IA 11/24, IB 5/24 IIIB in 2/24 and IV in 6/24. Five-year
      survival for the entire group was 65%. Patients with focal lesions had a longer
      survival. The survival in patients who underwent potentially curative resections
      was 62.8 +/- 44.0 months. When surgery was considered non-curative, survival was
      21.2 +/- 19.5 months (p = 0.0064). Five-year survival in stage IA patients was
      80%. Survival of patients with non-mucinous histology was longer than those with
      mucinous type carcinomas (54.9 +/- 25.0 months vs. 5.33 +/- 4.04, p < 0.0001) but
      the 5-year-survival was not statistically different. In conclusion, BAC has a
      favourable prognosis. The best survival rate was found in focal forms,
      represented by early tumor, nodes, metastasis (TNM) stages and non-mucinous BAC
      among the histological groups.

PMID- 16977967
TI  - HIV-1 genetic diversity in Argentina and early diagnosis of perinatal infection.
AB  - HIV-1 diagnosis of perinatally exposed children is usually performed by molecular
      biology-based methods, allowing the direct detection of the virus. Thus, HIV-1
      genomic variability within and across strains plays a major role in relation to
      the sensitivity of these tests, often leading to misdiagnosis. We describe the
      performance of an in-house multiplex nested PCR (nPCR) for early detection of HIV
      1 infection in perinatally exposed children born in Argentina, where the
      percentage of diverse BF recombinants is as high as 80%. After evaluation of 1316
      HIV-1 perinatally exposed children collected over a 7-year period, the
      specificity and sensitivity of the diagnostic nPCR was of 100% and 99.2%
      respectively, with only two false negative cases indicating a good performance of
      the diagnostic nPCR in the Argentine pediatric cohort. In search of unusual HIV-1
      subtypes among 22 HIV-1 infected cases presenting partial or complete HIV-1 gene
      amplification failure, we performed phylogenetic and recombination analysis of a
      vpu-env fragment in addition to gag and env Heteroduplex Mobility Assay
      screening. The most unusual findings included two subtypes A and a novel BC
      recombinant, while the majority of the strains were a variety of different BF
      recombinants. These results indicate the presence of novel and heterogeneous
      genotypes in our country and the need of continuous viral surveillance not only
      for diagnostic test optimization but also for the eventual implementation of a
      successful vaccine.

PMID- 16977968
TI  - [Prevalence of antinuclear envelope antibodies and their isotypes in sera
      positive for antinuclear antibodies].
AB  - Antinuclear antibodies detected in HEp-2 cells by indirect immunofluorescence
      assay display a great variety of images, including the nuclear envelope pattern.
      This is quite a less frequent finding. Two thousand five hundred and ninety-four
      sera were processed, and 37.6% of ANA were detected. The prevalence of anti
      nuclear envelope antibodies (ANEA) was of 1.2%, with a high association with
      autoimmune liver diseases (83%) and a low association with systemic lupus
      erythematosus. In 21 sera of patients with ANEA, no anti-DNAn antibodies were
      found; but 28.6% of anti-smooth muscle antibodies and 19% of anti-mitochondrial
      antibodies were detected. The triple rodent tissue section proved to be a less
      sensitive substrate than HEp-2 for the detection of ANEA. When using conjugates
      against different isotypes of antibodies for the detection of ANA, 90.5% of IgG,
      66.6% of IgA and 9.5% of IgM. Two patients had ANEA-IgA at high titers (> or =
      1:160) without ANEA-IgG. In this work, the importance of performing complementary
      tests for the detection of anti-smooth muscle antibodies, anti-mitochondrial
      antibodies and anti-DNAn is highlighted in order to apply these tests as
      guidelines for the clinical diagnosis of patients with ANEA. Besides, this study
      expresses the need of using total anti-Ig antibodies as conjugate for IIF-HEp-2
      instead of anti-lgG; until the role of IgA antibodies in these autoimmune
      diseases is clarified.

PMID- 16977969
TI  - [Limphomatous meningitis as recurrence site in Hodgkin's disease].
AB  - Intracraneal manifestations of Hodgkin's Disease (HD) are extremely rare, with an
      estimated incidence rate of approximately 0.5%. They can be classified as: 1)
      treatment-related leucoencephalopathy, 2) central nervous system infections, 3)
      paraneoplasic syndromes and 4) intracraneal lymphomas, which could be sub
      classified into intraparenchymal or intradural masses. We describe a case of a 40
      year-old male with mixed cellularity type HD who developed neurological
      manifestations as relapsed disease. Magnetic resonance imaging suggested
      leptomeningeal metastases and atypical cells were found in cerebrospinal fluid.
      The patient died from progressive disease refractory to third line chemotherapy.
      There are less than 50 similar cases reported in the literature. We review the
      clinical features and differential diagnosis of leptomeningeal metastases in
      Hodgkin's disease.

PMID- 16977970
TI  - [Pseudomigraine with pleocytosis].
AB  - The syndrome of transient headache and neurological deficits with cerebrospinal
      fluid lymphocytosis or pseudomigraine with temporary neurological symptoms and
      lymphocytic pleocytosis (HaNDL) is a syndrome consisting of recurrent headaches,
      reversible neurological deficit, lymphocytic pleocytosis in cerebrospinal fluid
      (CSF), variable duration over time and spontaneous resolution. Although several
      etiopathogenic mechanisms have been suggested (vascular, infectous, immunological
      and calcium channelopthy), its etiology remains unknown. We describe a 28 year
      old female, with recurrent migraine with pleocytosis, confusional syndrome and
      transient neurological deficit. The clinical remission was achieved within two
      months. Although its etiology remains unknown the differential diagnosis is
      discussed in order to keep in mind this syndrome.

PMID- 16977971
TI  - [Candida spondylodiscitis and epidural abscess].
AB  - Candida spondylodiscitis associatd with epidural abscess is rarely seen. We
      present a patient with Hodgkin lymphoma who received chemotherapy and developed
      systemic Candida infection, which was complicated by Candida spondylodiscitis and
      epidural abscess.

PMID- 16977972
TI  - [Infectious pseudoaneurism of the aorta].

PMID- 16977973
TI  - [Muscle metastases in lung cancer].

PMID- 16977974
TI  - [The new-world hantaviruses. Ecology and epidemiology of an emerging virus in
      Latin America].
AB  - The hantaviruses are a group of emerging rodent-borne pathogens (family
      Bunyaviridae; Genus Hantavirus) that are etiologic agents for hemorrhagic fever
      with renal syndrome (HFRS) in Europe and Asia and hantavirus cardiopulmonary
      syndrome (HCPS) in the Americas. HFRS is associated with rodents of the family
      Muridae, subfamilies Murinae and Arvicolinae; HPS is associated with rodents of
      the subfamily Sigmodontinae. Since the identification of HCPS in USA in 1993, a
      large number of cases of HPS and an increasing number of hantaviruses and rodent
      reservoir hosts have been identified in Central and South America. Epidemiologic
      studies have demonstrated important differences in frequency of infection with
      hantaviruses in both human and rodent host populations. Antibody prevalences in
      rodent and human populations may vary from less than 1% to more than 40%.
      Currently, more than 1500 cases of HCPS have been reported and more than 15
      genetically distinct variants of hantaviruses, all associated with sigmodontine
      rodents, have been identified throughout the Americas. Several characteristics
      distinguish Latin American HCPS cases from the classical HCPS described for the
      first time in the USA. These include a variation in severity of disease from
      moderate and self-limiting to severe, the demonstration of person-to-person
      transmission, and a somewhat higher incidence of extrapulmonary clinical
      manifestations in the South American form of HCPS. Nevertheless, our
      understanding of hantaviruses in the Americas is still far from complete. The
      factors involved in the dynamics of these viruses in nature, their establishment
      and transmission within host populations and from hosts to humans, and the
      variable pathology of these viruses in humans are complex. It is likely that more
      hantaviruses will be described in the future, and much more data will be required
      in order to describe the diversity and evolution of this group of pathogens.
      Latin America, as the center of diversity for Sigmodontine rodents and their
      hantaviruses is presented with the unique opportunity as well as the challenge of
      being center stage for continued studies of the dynamics of hantaviruses in
      natural host populations and the links of host and virus to human populations.

PMID- 16977975
TI  - [How do protein-glycan interactions regulate T-cell physiology?].
AB  - Recent evidence indicates that protein-glycan interactions play a critical role
      in different events associated with the physiology of T-cell responses including
      thymocyte maturation, T-cell activation, lymphocyte migration and T-cell
      apoptosis. Glycans decorating T-cell surface glycoproteins can modulate T-cell
      physiology by specifically interacting with endogenous lectins including
      selectins and galectins. These endogenous lectins are capable of recognizing
      sugar structures localized on T-cell surface glycoproteins and trigger different
      signal transduction pathways leading to differentiation, proliferation, cell
      cycle regulation or apoptosis. Protein-carbohydrate interactions may be
      controlled at different levels, including regulated expression of lectins during
      T-cell maturation and differentiation and the spatio-temporal regulation of
      glycosyltransferases and glycosidases, which create and modify sugar structures
      present in T-cell surface glycoproteins. This article briefly reviews the
      mechanisms by which protein-carbohydrate interactions modulate immunological
      processes such as T-cell activation, migration and apoptosis.

PMID- 16977976
TI  - [On the history of penicillin. The second line].

PMID- 16977977
TI  - [Umbilical cord blood criopreservation for autologous use. An ethical problem].

PMID- 16977978
TI  - [Freud was right about repression].

PMID- 16977979
TI  - [Argentine consensus for non-invasive ventilation].

PMID- 16977980
TI  - [Sepsis. Therapeutic strategies].

PMID- 16977982
TI  - Newt Gingrich: healthcare transformation advocate.

PMID- 16977983
TI  - Let's talk about health savings accounts....

PMID- 16977981
TI  - [Rectification].

PMID- 16977984
TI  - Weathering a financial storm.
AB  - After the effects of Hurricanes Katrina and Rita reached Texas, The University of
      Texas M.D. Anderson Cancer Center mapped out its disaster recovery: Assess the
      impact Develop a clinical recovery plan. Create capacity. Maintain control of
      expenses.

PMID- 16977985
TI  - ERISA and hospital charges: granting an inch, not a mile.
AB  - Some claims review services" have cited ERISA as an authority allowing an ERISA
      plan administrator to reduce a hospital's billed charges based on "the reasonable
      value of services." However, nothing in ERISA allows a plan administrator to
      change the terms of a contract between a payer and a provider, or places any
      limitations on the structure or price of hospital charges.

PMID- 16977986
TI  - The value of consulting in revenue cycle transformations: an analysis.
AB  - The most often cited benefits of revenue cycle consulting engagements are
      improved cash receipts and reduced A/R days, both cited by 61 percent of study
      respondents. Most providers expressed confidence in their ability to sustain the
      initial realized benefits. A key disadvantage cited was that such highly visible
      and politically charged engagements require focused management time and attention
      that may be difficult to sustain.

PMID- 16977987
TI  - Good documentation: what it means for your physicians--and your revenue cycle.
AB  - To powerfully influence physician documentation behavior--and improve patient
      care, reduce claim denials, and increase revenues: Examine each physician's
      documentation and coding habits and history through audits and, if possible, by
      observing physicians during typical patient encounters. Show physicians how they
      can improve record-keeping using specific examples from their own practices.
      Design encounter templates, superbills, and other documentation tools that
      address individual practice needs.

PMID- 16977988
TI  - Revenue cycle staff education: 3 views.
AB  - Hospital revenue cycle staff education programs should support skill development,
      address adult learning principles, and use cost-effective methods. Education
      programs should provide training for both new and existing employees. Educating
      revenue cycle staff reduces employee turnover, improves compliance, decreases
      denial write-offs, improves customer satisfaction, and increases point-of-service
      collections.

PMID- 16977989
TI  - Is your claim editor really working?
AB  - An analysis of 15 selected areas from publicly filed Medicare outpatient claims
      was performed to test the accuracy of claim editors. The analysis disclosed that
      in 2004, U.S. providers lost more than dollar 327 million of reimbursement due to
      errors in claims. Reimbursement was deemed "lost" only where it was obvious that
      billing errors had been made. Claims that included pathology exams had the
      greatest potential for lost revenue, because they often failed to account for the
      presence of specimen-removal procedures.

PMID- 16977990
TI  - An ounce of (pre-bill) prevention is worth a pound of (claims) cure.
AB  - Optimal revenue cycle health depends in part on effective eligibility and
      coverage verification, chargemaster maintenance, charge capture and
      documentation, and clinical soft coding. With appropriate technology,
      knowledgeable staff, and efficient processes, hospitals can "diagnose" their
      revenue cycle health.

PMID- 16977991
TI  - Battling bad debt.
AB  - Automated revenue cycle tools are giving hospitals the power to identify bad debt
      and charity cases as they access a facility and to dictate the appropriate course
      of action and workflow. To be successful, these tools must be regulatorily
      compliant and easily upgradeable, and should be accompanied by: Extensive staff
      training. An adjustment in workflow to match patient payment probability. Support
      of revenue cycle staff and physicians.

PMID- 16977992
TI  - Retrospective review: the good, the bad, and the ugly.
AB  - A rigorous retrospective review of a hospital's managed care contracts should
      include: Contract modeling. Revenue calculation. Reporting. Follow-up.

PMID- 16977993
TI  - All in a day's work.
AB  - CMS rules regarding what constitutes a patient day are inconsistent and often
      confusing. Hospitals and their advisers should have a clear understanding of
      CMS's rules regarding what constitutes a patient day, the impact of those rules
      on Medicare payment, and instances in which CMS's rules may be subject to
      challenge. Lack of familiarity with the finer points of these rules may result in
      substantial underpayments for services rendered.

PMID- 16977994
TI  - Adapting customer service to consumer-directed health care.
AB  - A growing number of hospitals are implementing new tools that provide convenient,
      more detailed patient access to billing information. These tools are paying off
      for hospitals through reduced calls to their billing offices, decreased mailing
      costs, and increased payments, as well as higher rates of customer satisfaction.

PMID- 16977995
TI  - Gainsharing: past, present, and future.
AB  - Gainsharing gives hospitals and physicians an opportunity to align their economic
      interests, and gives hospitals a means to improve operational efficiencies and
      quality of patient care by promoting the development of best practices. The OIG's
      2005 advisory opinions on hospital-physician gainsharing suggest that such
      arrangements are again open for hospitals to consider. Gainsharing arrangements
      likely to meet with the OIG's approval are those limited arrangements that are
      tied to specific, identifiable, and verifiable actions and cost savings.

PMID- 16977996
TI  - Assessing management and leadership in the hospital industry.

PMID- 16977997
TI  - Information-based transformation: the need for integrated, enterprisewide
      informatics.

PMID- 16977998
TI  - Reader feedback suggests market mess.

PMID- 16977999
TI  - Inflation: safeguarding your portfolio from the contagion.

PMID- 16978000
TI  - Consumer influence on technology investments.

PMID- 16978001
TI  - Outlier payments not as prevalent as headlines may suggest.

PMID- 16978002
TI  - Leading knowledge producers within the biomedical informatics community.
AB  - OBJECTIVES: To present findings on academic leadership within the biomedical
      informatics community based upon the number of research articles produced by
      authors, institutions, and countries within five biomedical informatics journals.
      METHODS: Five biomedical informatics journals were analyzed for the most
      producing author, institution, and country for two time periods: 1995-1999 and
      2000-2004. RESULTS: Results show that an overall trend exists whereby the
      academic leadership for author, institution, and country is the U.S. The results
      exist for both time periods of 1995-1999 and 2000-2004. CONCLUSIONS: Even though
      individual institutional and author rankings may have fluctuated within the two
      time periods (1995-1999 and 2000-2004), U.S. dominance at the institutional and
      author level remains significant within the five biomedical journals selected for
      this study.

PMID- 16978003
TI  - Racial disparities in health information access: resilience of the Digital
      Divide.
AB  - Policy initiatives of the late 1990s were believed to have largely eliminated the
      information "Digital Divide." For healthcare consumers, access to information is
      an essential part of the consumer-centric framework outlined in the recently
      proposed national health information initiative. This study sought to examine how
      racial/ethnic characteristics are associated with Internet use and online health
      information. Using a cross-sectional nationwide study of reported Internet use
      and information search in 2000 and 2002, we studied a stratified sample of
      computer users from the Pew Internet and American Life Project surveys. Adjusted
      estimates of race/ethnicity and income effects on Internet use and search
      behaviors were derived from generalized estimating equations. Results show wide
      gaps in the use of computers between Hispanics and Whites (OR = 0.593 [0.440,
      0.798]) and between African-Americans and Whites (OR = 0.554 [0.427, 0.720]) in
      2000 significantly narrowed in 2002 (OR of Hispanic to white = 1.250 [0.874,
      1.789]; OR of African-American to Whites = (0.793 [0.551, 1.141]). Gaps in access
      to the Internet, however, remained consistent between 2000-2002. Differences in
      health information seeking between Hispanics and Whites existed in both 2000 and
      2002. 56% of White Internet users at some time searched for online health
      information, whereas 42% of Hispanic Internet users did so in 2000. By 2002,
      these percentages had increased to 13.4 and 15.8%, respectively. Data highlight
      the persistence of "Digitally Underserved Groups," despite recent Divide
      reduction strategies.

PMID- 16978004
TI  - Assessing health consumerism on the Web: a demographic profile of information
      seeking behaviors.
AB  - The growing diversity of the online health information community is increasingly
      cited as a limiting factor related to the potential of the Internet as an
      effective health communication channel and information resource. Public-access
      Internet portals and decreasing costs of personal computers have created a
      consensus that unequal access to information, or a "Digital Divide," presents a
      like problem specific to health care consumers. Access to information, however,
      is an essential part of the consumer-centric framework outlined in the recently
      proposed U.S. National Health Information Infrastructure (NHII) and Health
      Architecture initiatives. To date little research has been done to differentiate
      the types of health information sought on the Web by different subgroups, linking
      user characteristics and health-seeking behaviors. Data from a study of consumer
      Web search activity in a post-intervention era serves as a natural experiment,
      and can identify whether a "digitally underserved group" persists in the United
      States. Such an environment would serve to exclude traditionally underserved
      groups from the benefits of the planned national heath information
      infrastructure. This exploratory technology assessment study seeks to
      differentiate and delineate specific behaviors, or lack of desired behaviors,
      across targeted health care subgroups. Doing so allows the design of more
      effective strategies to promote the use of the Web as a health education and
      health promotion tool, under the envisioned shared decision-making, consumer
      centric health information model.

PMID- 16978005
TI  - Incorporating an EPR system with a universal patient record.
AB  - Electronic Patient Record (EPR) systems could be built or changed to share a
      distributed universal patient medical record that would benefit health care in
      many ways.

PMID- 16978006
TI  - Comparison of computing capability and information system abilities of state
      hospitals owned by Ministry of Labor and Social Security and Ministry of Health.
AB  - The main purpose of this study is to give an idea to the readers about how big
      and important the computing and information problems that hospital managers as
      well as policy makers will face with after collecting the Ministry of Labor and
      Social Security (MoLSS) and Ministry of Health (MoH) hospitals under single
      structure in Turkey by comparing the current level of computing capability of
      hospitals owned by two ministries. The data used in this study were obtained from
      729 hospitals that belong to both ministries by using a data collection tool. The
      results indicate that there have been considerable differences among the
      hospitals owned by the two ministries in terms of human resources and information
      systems. The hospital managers and decision makers making their decisions based
      on the data produced by current hospital information system (HIS) would more
      likely face very important difficulties after merging MoH and MoLSS hospitals in
      Turkey. It is also possible to claim that the level and adequacy of computing
      abilities and devices do not allow the managers of public hospitals to use
      computer technology effectively in their information management practices. Lack
      of technical information, undeveloped information culture, inappropriate
      management styles, and being inexperienced are the main reasons of why HIS does
      not run properly and effectively in Turkish hospitals.

PMID- 16978007
TI  - Investigating response bias in an information technology survey of physicians.
AB  - Monitoring the diffusion of electronic health records (EHR) into ambulatory
      clinical practice has important policy implications. However, estimates of EHR
      use are typically derived from survey data and may be subject to significant
      response bias. The current study is a retrospective analysis testing for response
      bias in a large information technology survey of physicians (n = 14,921). To
      detect bias, respondents were compared to nonrespondents on known
      characteristics. Moreover, early respondents were compared to late respondents
      with respect to key variables in the survey that are likely to influence
      participation. The 4203 respondents (28.2% participation rate) did not differ
      demographically from nonrespondents. Response rates, by specialty, differed
      slightly. When comparing early and late survey respondents, no differences were
      detected in EHR use, length of time since EHR installation, practice size,
      physician age, years since medical school graduation, and years of practice in
      their current community. Overall, response bias was not detected using
      established methodologies in this mailed survey of physician EHR use. Similar
      surveys of physicians, even with a lower than expected response rate, may still
      be valid.

PMID- 16978008
TI  - Analysis of a territorial approach to the delivery of nursing home care services
      based on historical data.
AB  - We analyze a territorial approach to deliver nursing homecare services to a
      territory public health. We present the case of the CSSS assigned to Cote-des
      Neiges, Metro center and Parc Extension, specifically the case of the Cote-des
      Neiges site (CLSC CDN), where a territorial approach is used since 1980. We first
      give an historical comparison of patient visits delivered in 1998-1999 and in
      2002-2003. We follow with an in-depth analysis of the home services delivered in
      2002-2003 to determine whether or not the territorial approach can well support
      the changing needs of the population. We conclude that the territorial approach
      to deliver homecare nursing services does not sufficiently support fluctuations
      in population needs for services. Not only is it difficult to predict these
      fluctuations, but it is difficult to accurately quantify the true needs for
      services since the availability of nursing services tends to determine the
      services actually delivered. In sectors of the territory where resources are more
      scarce (based on previous population needs analyses) or demand for services is
      greater, the result is work overload for the nursing staff. In addition, this
      results in service delivery inequities across the entire territory. Therefore, a
      more dynamic assignment of clients to the nurses based on each nurse's work load
      and case load rather than based on the geographic location of clients is worth
      the extra administrative time in case assignment to ensure a more equitable case
      load attribution between nurses as well as less inequities between clients in
      terms of service delivery considering their needs.

PMID- 16978009
TI  - Adding value with 3D visualization and haptic forces to radiosurgery--a small
      theory-based, quasi-experimental study.
AB  - This study investigates the use of 3D representation and haptic technology in
      radiosurgery. The users, experienced users of the Leksell GammaKnife, prefer the
      3D representation for constructing a first draft of their plan for neurosurgical
      intervention. When it comes to the final adjustments, however, they still choose
      the traditional 2D representation and interaction devices. The perceived control
      over the radiosurgical process is not considered adequate using the 3D
      interaction methods. Practitioners do not consider the haptic forces implemented
      in this test system useful. Possible explanations for these findings are
      discussed in the paper.

PMID- 16978010
TI  - Nullification of electromagnetic radiation: 50 Hz artifact during
      electroencephalogram recording.
AB  - This paper discusses the 50-Hz artifact observed during EEG recording of three
      patients, using Mindset24 equipment in a biomedical laboratory along with other
      instruments. The artifact at 50 Hz is created due to electromagnetic (EM)
      radiation from the environment. Perhaps, the nullification of 50 Hz artifact
      occurs by the three important means such as (a) grounding of far-field EM current
      when the patient touches the equipment metal casing, (b) connecting the
      electrodes in a sequence to obtain differential potentials with suppressed near
      field EM radiation potentials of the scalp, and (c) destructive interferences of
      the EM waves.

PMID- 16978011
TI  - Personal health record systems and their security protection.
AB  - The objective of this study is to analyze the security protection of personal
      health record systems. To achieve this we have investigated different personal
      health record systems, their security functions, and security issues. We have
      noted that current security mechanisms are not adequate and we have proposed some
      security mechanisms to tackle these problems.

PMID- 16978012
TI  - Discontinuous region growing scheme for preliminary detection of tumor in MRCP
      images.
AB  - Tumors are generally difficult to detect in Magnetic Resonance (MR) images as
      they can be of varying intensities and do not appear as clear structures on these
      images. This difficulty is more prominent in MR Cholangiopancreatography (MRCP),
      which is the MR technology using a special sequence of T2-weighted imaging to
      identify the biliary tract, pancreatic duct, and gallbladder in the liver region,
      as MRCP images are more noisy in nature and are acquired for a more focused area
      with too much flexibility in position orientation for convenient computer-aided
      diagnosis. Based on the principle that the tumor mass manifests itself as
      blockage of the biliary tree structure, this paper introduces a technique that
      uses a region growing algorithm to identify discontinuities in the biliary tree
      as a means to preliminary detection of a possible tumor, in a fashion similar to
      the visual observation used by most radiologists in making their preliminary
      diagnosis. Through the use of appropriate image normalization, watershed
      segmentation, thresholding, rule-based region growing, and region analysis, the
      proposed technique is shown in this paper to be successful in identifying MRCP
      images with liver carcinoma from those with normal liver. Acquisition
      standardization, interactive image selection, and optimum image orientation will
      further enhance the accuracy of this proposed scheme for use in aiding clinical
      diagnosis at medical institutions.

PMID- 16978013
TI  - Molecular mimicry as a mechanism for the uptake of cysteine S-conjugates of
      methylmercury and inorganic mercury.

PMID- 16978015
TI  - Future of toxicology--a shift in the paradigm: focus on human disease.

PMID- 16978017
TI  - Identification of a cis-2-butene-1,4-dial-derived glutathione conjugate in the
      urine of furan-treated rats.
AB  - The hepatocarcinogen and toxicant furan requires metabolic activation to elicit
      its toxic effects. The available experimental evidence indicates that the overall
      metabolism of furan is initiated via cytochrome P450 catalyzed oxidation to cis-2
      butene-1,4-dial. This alpha,beta-unsaturated dialdehyde reacts in vitro with
      protein and DNA nucleophiles. To determine if this compound is an in vivo
      intermediate in the metabolism of furan, rats were treated with either
      [(12)C(4)]furan or [(13)C(4)]furan, and urine was collected for 24 h. Capillary
      LC/MS/MS analysis of the urine indicated that one of the metabolites was a
      monoglutathione conjugate of cis-2-butene-1,4-dial. These results indicate that
      glutathione conjugation of the reactive metabolite of furan occurs in vivo. This
      metabolite may serve as a useful marker for furan exposure and metabolism in risk
      assessment studies.

PMID- 16978016
TI  - Bioactivation of Selective Estrogen Receptor Modulators (SERMs).

PMID- 16978018
TI  - Serine hydrolase KIAA1363: toxicological and structural features with emphasis on
      organophosphate interactions.
AB  - Serine hydrolase KIAA1363 is highly expressed in invasive cancer cells and is the
      major protein in mouse brain diethylphosphorylated by and hydrolyzing low levels
      of chlorpyrifos oxon (CPO) (the activated metabolite of a major insecticide). It
      is also the primary CPO-hydrolyzing enzyme in spinal cord, kidney, heart, lung,
      testis, and muscle but not liver, a pattern of tissue expression confirmed by
      fluorophosphonate-rhodamine labeling. KIAA1363 gene deletion using homologous
      recombination reduces CPO binding, hydrolysis, and metabolism 3-29-fold on
      incubation with brain membranes and homogenates determined with 1 nM [(3)H
      ethyl]CPO and the inhibitory potency for residual CPO with butyrylcholinesterase
      as a biomarker. Studies with knockout mice further show that KIAA1363 partially
      protects brain AChE and monoacylglycerol lipase from CPO-induced in vivo
      inhibition. Surprisingly, mouse brain KIAA1363 and AChE are similar in in vitro
      sensitivity to seven methyl, ethyl, and propyl but not higher alkyl OP
      insecticides and analogues, prompting structural comparisons of the active sites
      of KIAA1363 and AChE relative to OP potency and selectivity. Homology modeling
      based largely on the Archaeoglobus fulgidus esterase crystal structure indicates
      that KIAA1363 has a catalytic triad of S191, D348, and H378, a GDSAG motif, and
      an oxyanion hole of H113, G114, G115, and G116. Excellent selectivity for
      KIAA1363 is achieved on OP structure optimization with long alkyl chain
      substituents suggesting that KIAA1363 has larger acyl and leaving group pockets
      than those of AChE. KIAA1363 reactivates faster than AChE presumably due to
      differences in the uncoupling of the catalytic triad His upon phosphorylation.
      The structural modeling of KIAA1363 helps us understand OP structure-activity
      relationships and the toxicological relevance of this detoxifying enzyme.

PMID- 16978019
TI  - Capillary electrophoresis monitors enhancement in subcellular reactive oxygen
      species production upon treatment with doxorubicin.
AB  - This study investigated the role of doxorubicin (DOX) accumulation in reactive
      oxygen species (ROS) production detected in individually electrophoresed
      organelles, including mitochondria, acidic organelles, and peroxisomes. While
      bulk measurements of ROS production in cells and organelles are not capable of
      discriminating between the effects of preparative procedures on measured ROS
      production, capillary electrophoresis with dual laser-induced detection of
      individual organelles demonstrated a difference in the measured ROS production as
      a result of various preparative procedures. Using this technique, the three
      different types of detected organelles (i) produce ROS and do not have detectable
      levels of DOX, (ii) contain detectable DOX but do not produce ROS, or (iii)
      produce ROS and accumulate DOX. The third type displays two subpopulations of
      organelles, one of which demonstrated a direct relationship between DOX uptake
      and subsequent ROS production, corresponding most likely to mitochondria, and a
      second one with low DOX uptake but large variation in ROS production,
      corresponding most likely to acidic organelles.

PMID- 16978020
TI  - Nitroxidative, nitrosative, and nitrative stress: kinetic predictions of reactive
      nitrogen species chemistry under biological conditions.
AB  - A freely available Windows-based program, RNSim1A, is utilized to predict metal
      independent reactive nitrogen species (RNS) chemistry (oxidation, nitrosation,
      and nitration) under simulated biological conditions and make the following
      specific predictions. (1) The peak in oxidative reactions that occurs in vitro
      with 1:1 fluxes of (*)NO and O(2)(*)(-) does not occur under biological
      conditions. (2) By far, the quantitatively dominant (92-99.6%) process in vivo is
      oxidation, compared to nitrosation and nitration. (3) Only five of the many
      possible RNS reactions involving thiol (glutathione, GSH) and tyrosine are
      quantitatively important biologically. (4) Under inflammatory conditions,
      approximately 1% of O(2)(*)(-) reacts with (*)NO to produce ONOO(-), with the
      remainder reacting with SOD. (5) The dominant reaction of tyrosyl radical is a
      radical swap with GSH, producing the glutathiyl radical and regenerating
      tyrosine. (6) Nitrosothiol is formed virtually exclusively via radical
      recombination (RS(*) + (*)NO) as opposed to reaction with nitrous anhydride
      (N(2)O(3)). (7) Nitrosothiol is an intermediate, not an endproduct, and responds
      dynamically to changes in the immediate chemical environment. (8) The formation
      of a nitroso group on a particular thiol can be considered a marker of increased
      reactivity of that thiol, and it is likely that other modifications of that thiol
      (oxidation, glutathiolation) are more abundant than nitrosation and may be the
      functionally significant modification. (9) Specific chemical mechanisms are
      proposed for posttranslational protein modification via nitrosation, nitration,
      glutathiolation, and also dithiol/disulfide exchange, with important roles for
      the thiolate anion and O(2) (suggesting possible mechanisms for O(2) sensing) and
      variable degrees of exposure of cysteine thiol and tyrosine phenolate. (10)
      Patterns of reactivity are similar for low (20 nM) and high (500 nM) steady-state
      levels of NO. (11) The dominant reactions are those involving reactants at the
      highest concentrations (CO(2), thiol, O(2)). Because of the dominance of
      oxidative processes caused by RNS, the term nitroxidative stress is proposed,
      emphasizing the oxidative (as opposed to nitrosative or nitrative) stress that
      dominates RNS actions under biological conditions.

PMID- 16978021
TI  - Application of metabonomics in a compound ranking study in early drug development
      revealing drug-induced excretion of choline into urine.
AB  - Selecting drug candidates based on toxicity is an important step in early drug
      development. In this case study, it is shown how metabonomics is applied to a
      ranking study, in which drug candidates with equal pharmacological activities are
      selected based on least toxic side effects. The metabonomic analyses were carried
      out on an animal study that followed an established protocol for pilot
      toxicology/ranking studies in rats, however, not specifically modified for a
      metabonomic assessment. It is shown how conditions not specificially adopted for
      metabonomics investigations can significantly influence the metabolic profiles
      recorded by NMR. Furthermore, it is shown how the multivariate analysis of the
      NMR spectra identified an extreme excretion of an endogenous metabolite into
      urine induced by two out of the five drug candidates. The subsequent structure
      elucidation by two-dimensional NMR experiments and a subsequent validation by
      spiking experiments identified the metabolite as choline. The discussion of the
      mechanistic background for the excretion of choline, which is usually well
      conserved in the body, results in two hypotheses of either a massive degradation
      of cell membranes or an inhibition of the choline oxidation. Although the
      validation of these hypotheses needs a follow-up study, the finding of a
      increased excretion of the important metabolite choline warrants exclusion of
      these two compounds as viable drug candidates from a metabonomics point of view.

PMID- 16978022
TI  - Insights into the o-acetylation reaction of hydroxylated heterocyclic amines by
      human arylamine N-acetyltransferases: a computational study.
AB  - A computational study was performed to better understand the differences between
      human arylamine N-acetyltransferase (NAT) 1 and 2. Homology models were
      constructed from available crystal structures, and comparisons of the active site
      residues 125, 127, and 129 for these two enzymes provide insight into observed
      substrate differences. The NAT2 model provided a basis for understanding how some
      of the common polymorphisms may affect the structure of this protein. Molecular
      dynamics simulations of the human NAT models and the template structure (NAT from
      Mycobacterium smegmatis) were performed and showed the models to be stable and
      reasonable. Docking studies of hydroxylated heterocyclic amines in the models of
      NAT1 and NAT2 probed the differences exhibited by these two proteins with
      mutagenic agents. The hydroxylated heterocyclic amines were only able to fit into
      the NAT2 active site, and an alternative binding site by the phosphate-binding
      loop was found using our models and will be discussed. Quantum mechanical
      calculations on the O-acetylation reaction of the hydroxylated heterocyclic
      amines N-OH MeIQx and N-OH PhIP show that the reaction coordinates differ for
      these two compounds, but the activation barrier separating the reactant from the
      product are both low. The results of this study suggest that common polymorphisms
      in human NAT2 are distant from the active site and are more likely to destabilize
      the enzyme than affect catalysis. Additionally, the quantum mechanical
      calculations show that the observed differences in mutagenic activity between N
      OH MeIQx and N-OH PhIP are not related to their acetylation reaction with NAT.

PMID- 16978023
TI  - Quantification of aflatoxin-B1-N7-Guanine in human urine by high-performance
      liquid chromatography and isotope dilution tandem mass spectrometry.
AB  - We report validation of the first isotope dilution mass spectrometry method for
      determination of aflatoxin B(1)-N(7)-guanine (AFB(1)-N(7)-Gua), a major human
      aflatoxin-DNA adduct that is excreted in the urine. Measurement of urinary AFB(1)
      N(7)-Gua, a biomarker of the biologically effective dose following dietary
      aflatoxin B(1) (AFB(1)) exposure, has helped identify AFB(1) as a risk factor in
      the development of hepatocellular carcinoma, a common cancer worldwide. Triple
      quadrupole mass spectrometry, coupled with the use of a stable isotope-labeled
      internal standard (AFB(1)-N(7)-(15)N(5)-Gua) and better solid phase extraction
      and immunoaffinity column chromatography, have enabled us to greatly improve
      accuracy, precision, specificity, and sensitivity over previously published
      determinations. The limit of quantitation for AFB(1)-N(7)-Gua was 0.8 pg/20 mL
      urine (0.07 pg/mg creatinine). The method was validated for accuracy and
      precision over the range of 0.8-25 pg/20 mL urine, with between-day and within
      day reproducibility for analysis of six aliquots of a human urine sample
      containing 6.0 pg/20 mL measured at <6% coefficient of variation. AFB(1)-N(7)-Gua
      concentrations were measured in 20 human urine samples collected in a region with
      known aflatoxin exposure. The mean concentration of AFB(1)-N(7)-Gua, measured in
      16/20 urine samples with levels above the method's limit of quantitation, was 2.9
      pg/20 mL urine (0.28 pg/mg creatinine) with a range of <0.8-7.2 pg/20 mL urine
      (0.04-65 pg/mg creatinine). With improved accuracy and precision, this sensitive
      biomarker for recent human exposure to AFB(1) will be especially useful for
      measuring the efficacy of planned interventions to reduce aflatoxin-related liver
      cancer in AFB(1)-exposed populations.

PMID- 16978024
TI  - Ebselen, a seleno-organic antioxidant, as an electrophile.
AB  - Ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one], a seleno-organic compound
      showing glutathione peroxidase-like activity, is one of the promising synthetic
      antioxidants. In the present study, we investigated the electrophilic potential
      of this antioxidant and established the mechanism of the cysteine-targeted
      oxidation of protein. In addition, using ebselen as an electrophilic probe, we
      characterized the cysteine residues required for posttranslational modification
      into an electrophile sensor protein in the phase 2 detoxification response.
      Ebselen showed a potent antioxidant effect against the spontaneous and 4-hydroxy
      2-nonenal-stimulated production of intracellular reactive oxygen species in rat
      liver epithelial RL34 cells. Meanwhile, upon in vitro incubation with a redox
      active sulfhydryl protein (thioredoxin), ebselen showed a strong electrophilic
      potential of mediating the formation of selenenylsulfide and intra- and
      intermolecular disulfide linkages within the protein. By taking advantage of this
      antioxidant and electrophilic property of ebselen, we characterized
      posttranslational modification of Kelch-like ECH-associated protein 1 (Keap1), an
      electrophile sensor protein, which represses the ability of the transcription
      factor NF-E2-related factor 2 (Nrf2) upon induction of the phase 2 detoxification
      response. Ebselen potently induced the gene expression of a series of phase 2
      enzymes in rat liver epithelial RL34 cells, which was associated with the
      formation of a high molecular weight complex of Keap1. Furthermore, a cysteine
      residue in Keap1, C151, was found to be uniquely required not only for the
      formation of the complex but also for the induction of the phase 2 response by
      ebselen. Thus, this unique antioxidant and electrophilic property of ebselen
      giving rise to the cysteine-targeted oxidation enabled us to evaluate the role of
      sensor cysteines in redox regulation of protein function under electrophile
      stress.

PMID- 16978025
TI  - Study of the sequence of events involved in nevirapine-induced skin rash in Brown
      Norway rats.
AB  - Nevirapine, used for the treatment of HIV infection, is associated with
      development of skin rash and liver toxicity. The mechanism of these idiosyncratic
      reactions is unknown. We have previously reported the discovery of a new animal
      model of nevirapine-induced skin rash in rats. When treated with nevirapine,
      Brown Norway rats developed red ears on about day 7 and skin rash on about day
      21. On rechallenge, ears turn red within 24 h, and skin lesions develop by day 9.
      In the current study, we analyzed the time course of the sequence of events
      involved in the development of skin rash. Rats were treated with nevirapine for
      7, 14, or 21 days or rechallenged with it for 0, 1, or 9 days. This treatment led
      to an increase in the total number of auricular lymph node T, B, and macrophage
      cells. There was also an increase in the activation/infiltration marker ICAM-1
      and activation/antigen presentation marker MHC II in these cells compared with
      those from control rats. Immunohistochemistry analysis showed macrophage
      infiltration and ICAM-1 expression in the ears of treated rats as early as day 7
      of treatment. Macrophage infiltration preceded T cell infiltration, which was not
      apparent until the onset of rash. Both MHC I and MHC II expression increased in
      the skin of nevirapine-treated rats that developed rash. A major inducer of MHC
      is IFNgamma. Although rechallenge with nevirapine led to a large increase in
      serum levels of IFNgamma, this was not observed during the treatment of naive
      rats with nevirapine. These observations provide further clues to the mechanism
      of nevirapine-induced skin rash.

PMID- 16978026
TI  - Transcription arrest at an abasic site in the transcribed strand of template DNA.
AB  - A dedicated excision repair pathway, termed transcription-coupled repair (TCR),
      targets the removal of DNA lesions from transcribed strands of expressed genes.
      Transcription arrest at the site of the lesion has been proposed as the first
      step for initiation of TCR. In support of this model, a strong correlation
      between arrest of transcription by a lesion in vitro and TCR of that lesion in
      vivo has been found in most cases analyzed. TCR has been reported for oxidative
      DNA damage; however, very little is known about how frequently occurring and
      spontaneous DNA damage, such as depurination and base deamination, affects
      progression of the transcription complex. We have previously determined that the
      oxidative lesion, thymine glycol, is a significant block to transcription by T7
      RNA polymerase (T7 RNAP) but has no detectable effect on transcription by RNA
      polymerase II (RNAP II) in a reconstituted system with all of the required
      factors. Another oxidative lesion, 8-oxoguanine, only slightly blocked T7 RNAP
      and caused RNAP II to briefly pause at the lesion before bypassing it. Because an
      abasic site is an intermediate in the repair of oxidative damage, it was of
      interest to learn whether it arrested transcription. Using in vitro transcription
      assays and substrates containing a specifically positioned lesion, we found that
      an abasic site in the transcribed strand is a 60% block to transcription by T7
      RNAP but nearly a complete block to transcription by mammalian RNAP II. An abasic
      site in the nontranscribed strand did not block either polymerase. Our results
      clearly indicate that an abasic site is a much stronger block to transcription
      than either a thymine glycol or an 8-oxoguanine. Because the predominant model
      for TCR postulates that only lesions that block RNAP will be subject to TCR, our
      findings suggest that the abasic site may be sufficient to initiate TCR in vivo.

PMID- 16978027
TI  - Cytotoxicity and cytoprotective activity of naphthalenediols in rat cortical
      neurons.
AB  - Some members of the naphthalenediol family have been shown in previous work on PC
      12 cells to act as effective antioxidants while being relatively nontoxic. In the
      present work, we extend that study to examine the effect of naphthalenediols on
      rat primary cortical neurons exposed to AAPH (2,2'-azobis (2-amidinopropane)
      hydrochloride), a source of peroxyl radicals. Compounds tested included the
      acetylated forms of 1,2-naphthalenediol, that is, 1,2-ND, as well as 1,4-ND, 2,3
      ND, 1,8-ND, and the known highly potent antioxidant (-)-epigallocatechin gallate
      (EGCG). In cytoxicity studies, cells were exposed to the compounds for 24 h,
      leading to observed toxicity in the order of 1,4-ND > 1,2 ND >> 2,3-ND
      approximately EGCG > 1,8-ND. In cytoprotection studies, the desired compounds
      were incubated with neurons prior to AAPH exposure, and live cell counts were
      determined by trypan blue and/or MTT assays. Excellent protection, superior to
      EGCG, was provided by 2,3-ND and 1,8-ND. Additional studies using glutamate as a
      stressor showed that 1,8-ND had a significant protective effect at concentrations
      as low as 500 nM. The results can be understood on the basis of the tendency (or
      lack thereof) to form the corresponding quinone, which in turn depends on whether
      or not there is a loss of aromaticity in the ring adjacent to the quinone moiety.
      Thus, certain members of the family of naphthalenediols are quite cytotoxic,
      whereas others show promise as neuroprotective antioxidants.

PMID- 16978028
TI  - Mechanistic applicability domains for non-animal based prediction of
      toxicological endpoints. QSAR analysis of the schiff base applicability domain
      for skin sensitization.
AB  - Several recent (1999 onward) publications on skin sensitization to aldehydes and
      ketones, which can sensitize by covalent binding to skin protein via Schiff base
      formation, present QSARs based on the Taft sigma parameter to model reactivity
      and log P to model hydrophobicity. Here, all of the data are reanalyzed together
      in a stepwise self-consistent way using the parameters log P (octanol/water) and
      Sigmasigma, the latter being the sum of Taft sigma values for the two groups R
      and R' in RCOR'. A QSAR is derived: pEC3 = 1.12(+/-0.07) Sigmasigma + 0.42(+/
      0.04) log P - 0.62(+/-0.13); n = 16 R(2) = 0.952 R(2)(adj) = 0.945 s = 0.12 F =
      129.6, based on mouse local lymph node assay (LLNA) data for 11 aliphatic
      aldehydes, 1 alpha-ketoester and 4 alpha,beta-diketones. In developing this QSAR,
      an initial regression equation for a training set of 10 aldehydes was found to
      predict a test set consisting of the other 6 compounds. The QSAR is found to be
      well predictive for LLNA data on a series of alpha,gamma-diketones and also
      correctly predicts the nonsensitizing properties of simple dialkylketones. It is
      shown to meet all of the criteria of the OECD principles for applicability within
      regulatory practice. In view of the structural diversity within the sets of
      compounds considered here, the present findings confirm the view that within the
      mechanistic applicability domain the differences in sensitization potential are
      dependent solely on differences in chemical reactivity and partitioning.

PMID- 16978029
TI  - Quantitation of N-acetyl-S-(9,10-dihydro-9-hydroxy-10-phenanthryl)-L-cysteine in
      human urine: comparison with glutathione-S-transferase genotypes in smokers.
AB  - There are major interindividual differences in carcinogenic polycyclic aromatic
      hydrocarbon (PAH) metabolism in humans, and it has been hypothesized that these
      differences may be related to cancer risk in smokers and other exposed people.
      One important pathway of PAH metabolism involves the detoxification of the
      epoxide and diol epoxide metabolites by reaction with glutathione, catalyzed by
      glutathione-S-transferases (GSTs). Interindividual differences in these pathways
      have been examined by genotyping methods, investigating polymorphisms in GSTM1
      and GSTP1. We are developing a phenotyping approach to assessing individual
      differences in PAH metabolism by quantifying human urinary metabolites of the
      ubiquitous PAH phenanthrene (1). In this study, we developed a method for
      quantitation of a mercapturic acid, N-acetyl-S-(9,10-dihydro-9-hydroxy-10
      phenanthryl)-l-cysteine (PheO-NAC, 12), the end product of the reaction of
      phenanthrene-9,10-epoxide (11) with glutathione. [D(10)]PheO-NAC was added to the
      urine as internal standard, and the PheO-NAC fraction was enriched by solid-phase
      extraction. PheO-NAC was quantified by liquid chromatography electrospray
      ionization tandem mass spectrometry with selected reaction monitoring. The
      detection limit was approximately 4 fmol/mL of urine. PheO-NAC was detected in
      the urine of 46 of 104 smokers, mean (S.D.) 57.9 +/- 144 fmol/mL. PheO-NAC was
      detected significantly more frequently (P < 0.0001) in subjects who were GSTM1
      positive than in those who were GSTM1 null, and the levels of PheO-NAC were
      significantly higher in the GSTM1 positive subjects, consistent with a role for
      GSTM1 in the detoxification of phenanthrene-9,10-epoxide. There were no
      significant relationships between PheO-NAC levels and the occurrence of two GSTP1
      polymorphisms. The results of this study provide the first evidence for a PAH
      derived mercapturic acid in human urine and should be useful in the development
      of a phenotyping approach to assess individual differences in PAH metabolism.

PMID- 16978030
TI  - Genotoxicity of the hydroquinone metabolite of ochratoxin A: structure-activity
      relationships for covalent DNA adduction.
AB  - Ochratoxin A (OTA) is a mycotoxin that shows potent nephrotoxicity and renal
      carcinogenicity in rodents. One hypothesis for OTA-induced tumor formation is
      based on its genotoxic properties that are promoted by oxidative metabolism. Like
      other chlorinated phenols, OTA undergoes an oxidative dechlorination process to
      generate a quinone (OTQ)/hydroquinone (OTHQ) redox couple that may play a role in
      OTA-mediated genotoxicity. To determine whether the OTQ/OTHQ redox couple of OTA
      contributes to genotoxicity, the DNA adduction properties, as evidenced by the
      (32)P-postlabeling technique, of the hydroquinone analogue (OTHQ) have been
      compared to OTA in the absence and presence of metabolic activation (pig kidney
      microsomes) and within human bronchial epithelial (WI26) and human kidney (HK2)
      cells. Our experiments show that OTHQ generates DNA adduct spots in the absence
      of metabolic activation. These adducts are ascribed to covalent DNA adduction by
      OTQ generated through autoxidation of the hydroquinone precursor, OTHQ. Although
      OTA does not interact with DNA in the absence of metabolism, the OTQ-mediated DNA
      adduct spots noted with OTHQ are also observed with OTA following treatment with
      pig kidney microsomes and NADPH, suggesting that OTA undergoes oxidative
      activation to OTQ by cytochrome P450 or enzymes with peroxidase activity.
      Comparison of DNA adduction by OTHQ and OTA in human cell lines shows that OTQ
      mediated adduct spots form in a dose- and time-dependent manner. The adduct spots
      form at a faster rate with OTHQ, which is consistent with more facile generation
      of OTQ from its hydroquinone precursor. These results establish structure
      activity relationships for OTA-mediated DNA adduction and provide new evidence
      for the potential role of the OTQ/OTHQ redox couple in OTA-induced genotoxicity.

PMID- 16978031
TI  - Synthesis and reactivity toward nucleophilic amino acids of 2,5-[13C]-dimethyl-p
      benzoquinonediimine.
AB  - 2,5-[(13)C]-Dimethyl-p-benzoquinonediimine was synthesized, and its reactivity
      toward several nucleophilic amino acids was studied by associated (13)C and
      (1)H{(13)C} NMR spectroscopies, combined with HPLC in tandem with mass
      spectrometry. A classical electrophile-nucleophile mechanism was observed for the
      reaction with N-acetyl-Cys. Adducts resulted from the reaction of the amino acid
      thiol group with the benzoquinonediimine electrophilic positions 3 and 6 as well
      as with the nitrogen atom of the imino group. However, N-acetyl-Trp and N-acetyl
      Lys were chemically modified in the presence of 2,5-[(13)C]-dimethyl-p
      benzoquinonediimine through the involvement of oxido-reduction processes.
      Heteronuclear (1)H{(13)C} NMR experiments allowed the identification of known
      oxidation intermediates derived from N-acetyl-Trp, indicating the oxidative
      strength of the reaction media. An adduct resulted from the reaction between the
      reduced form of the benzoquinonediimine and N-acetyl-formylkynurenine, which is
      the most known oxidation derivative of N-acetyl-Trp. In the case of N-acetyl-Lys,
      4-amino-2,5-dimethyl-[(13)C]-formanilide and its derivative with N-acetyl-Lys at
      position 4 were obtained. A reaction mechanism was suggested in which the epsilon
      NH(2) of the amino acid reacted on the electrophilic diimine to form an enamine
      adduct, which could then induce an oxidative deamination of N-acetyl-Lys. Further
      oxido-reduction mechanisms on the N-acetyl-alpha-aminoadipate-delta-semialdehyde
      formed might afford N,N-acetyl-formyl glutamic semialdehyde, which was considered
      as the powerful reactive species toward the reduced form of 2,5-[(13)C]-dimethyl
      p-benzoquinonediimine. In the presence of N-acetyl-Tyr or N-acetyl-Met, the
      hydrolysis of the diimine parent compound was preferred, followed by a reduction
      to the hydroquinone form. In this study, we have thus shown that p
      benzoquinonediimines, the first oxidation derivatives of allergenic p-amino
      aromatic compounds, can react with nucleophilic residues on amino acids through a
      set of complex mechanisms and must be seriously considered as potential
      candidates for the formation of antigenic structures responsible for allergic
      contact dermatitis.

PMID- 16978032
TI  - The role of topical immune response modifiers in skin cancer.
AB  - Topical immune response modifiers include imiquimod and resiquimod. The mechanism
      of action of immune response modifiers is complex and not completely understood.
      It involves the stimulation of innate and cell-mediated immune responses through
      Toll-like receptor-mediated induction of cytokines. Imiquimod is approved for the
      treatment of actinic keratoses, superficial basal cell carcinomas and warts; it
      has also been documented to successfully treat other forms of skin cancer such as
      squamous cell carcinoma in situ, melanoma and extramammary Paget's disease.

PMID- 16978033
TI  - Immunotherapy for De Novo renal transplantation: what's in the pipeline?
AB  - Immunosuppressive drugs have been traditionally developed to prevent acute
      rejection and to improve short-term kidney transplant outcomes. There is still a
      medical need to improve outcomes among subgroups of patients at higher risk for
      graft loss and to reduce cardiovascular, infectious and malignancy-associated
      morbidity and mortality, and improve long-term adherence. Several new
      immunosuppressive agents and formulations are undergoing clinical investigation
      and are discussed in this review.A modified release tacrolimus formulation (MR4)
      for once-daily administration is undergoing phase III trials. It has been
      developed to be administered de novo or for maintenance using the same
      therapeutic target tacrolimus trough concentrations as for the original
      formulation. Belatacept (LEA29Y), a second generation cytotoxic-T-lymphocyte
      associated antigen immunoglobulin (CTLA4-Ig), blocks the interaction between
      CD80/86 and CD28 costimulatory pathways. In phase II trials, belatacept was as
      effective as ciclosporin (cyclosporine) when administered in combination with
      basiliximab, mycophenolate mofetil (MMF) and corticosteroids. Currently,
      belatacept is undergoing phase III trials including one study in recipients of
      organs from expanded criteria donors. Inhibitors of the Janus protein tyrosine
      kinase (JAK)-3 show some selectivity for cells of the lymphoid lineage and have
      been shown to be effective in late preclinical transplant models. The most
      frequent adverse effects have been related to nonspecific binding to JAK2
      kinases. CP-690550, a JAK3 inhibitor is currently in phase II clinical
      trials.FK778, is a synthetic malononitrilamide that targets the critical enzyme
      of the de novo pyrimidine synthesis, dihydroorotic acid dehydrogenase, and
      receptor-associated tyrosine kinases has completed phase II trials. FK778 also
      shows antiviral activities that have been tested in patients with polyomavirus
      nephropathy. Fingolimod (FTY720), a synthetic sphingosine phosphate receptor
      modulator that reduces the recirculation of lymphocytes to blood and peripheral
      tissues including inflammatory lesions and graft sites is undergoing phase III
      trials. Although the efficacy of fingolimod is similar to MMF in patients
      receiving full doses of ciclosporin, safety issues such as a negative
      chronotropic effect, macular oedema, pulmonary adverse reactions and graft
      function resulted in premature discontinuation of the development programme for
      kidney transplantation. Because there was no clear clinical benefit over
      treatment options, the clinical development programme of FK778 was
      discontinued.Finally, a new evolving strategy with powerful induction-induced
      prolonged T-cell depletion followed by low-dose immunosuppressive monotherapy is
      showing promising results.

PMID- 16978034
TI  - Pharmacological treatments for thyroid eye disease.
AB  - Thyroid eye disease (TED), which affects the majority of patients with Grave's
      disease, is associated with significant ophthalmic morbidity. In patients with
      mild disease, supportive treatment with lubricating medication can be sufficient.
      However, in patients with severe TED and disfiguring proptosis or sight
      threatening neuropathy, more aggressive medical or surgical interventions are
      necessary. Corticosteroids remain the preferred pharmacological treatment
      modality in the majority of patients with an active inflammatory component. Other
      immunosuppressive drugs in combination with corticosteroids may be helpful in
      patients with corticosteroid-resistant TED. Newer agents such as somatostatin
      analogues have not shown to be of significant clinical benefit; however, initial
      studies on the use of antioxidants and cytokine antagonists are encouraging.

PMID- 16978035
TI  - Management of focal-onset seizures: an update on drug treatment.
AB  - Focal-onset seizures are manifestations of abnormal epileptic firing of brain
      cells in a localised area or areas of the brain. The diagnosis of focal-onset
      seizures initially entails an EEG, a detailed history from the patient and
      eyewitnesses, as well as computer tomographic or, preferably, magnetic resonance
      imaging scans. Video EEG to record ictal events may be necessary to establish the
      correct diagnosis. Focal seizures are classified according to the International
      Classification of Epileptic Seizures and International Classification of
      Epilepsies and Epilepsy Syndromes. It is important to try to decide how the
      seizure event fits into this system in order to successfully evaluate and
      optimise treatment, as well as to give detailed information to the patient about
      their seizures and prognosis. Once the decision to treat the seizures has been
      made, the physician must choose which medication is the most appropriate to begin
      with. Carbamazepine, phenytoin or valproic acid (sodium valproate) are often
      rated as first-line drugs, but factors such as adverse-effect profiles, age,
      possibility of pregnancy, and concomitant diseases and medication also need to be
      considered. Most of the newer antiepileptic drugs (AEDs) appear to have good
      efficacy and better tolerability than the older agents, but evidence to support
      their superiority is scarce and has led to conflicting advice in several
      guidelines. Among the newer AEDs, lamotrigine, gabapentin, topiramate and
      oxcarbazepine have obtained monotherapy indication in many countries. The higher
      costs of the newer AEDs may inhibit their wider use, especially in poorer
      countries.

PMID- 16978036
TI  - Cardiovascular health and aromatase inhibitors.
AB  - Cardiovascular disease is the most frequent cause of death in North American
      women, and so death resulting from cardiovascular disease, rather than from
      malignancy, is not uncommon in breast cancer patients. This may be a consequence
      of the shared risk factors for developing breast cancer and cardiovascular
      disease, as well as the difficulty of managing cancer patients at higher risk for
      developing cardiovascular disease. Recently, much attention has focused on
      understanding the cardiovascular risk factors associated with breast cancer
      therapies. Tamoxifen has a lowering effect on serum lipids and is reported to
      decrease the risk of myocardial infarction but to increase the risk of
      thromboembolic events. Current data indicate that aromatase inhibitors (AIs) are
      not associated with an increased risk of thromboembolic or cerebrovascular
      events. Reports of a greater incidence of hypercholesterolaemia when AIs are
      compared head-to-head with tamoxifen may be a result of the intrinsic lipid
      lowering effects of tamoxifen therapy and may be confounded by differences in
      data collection among trials. The incidence of cardiovascular events associated
      with AIs in large trials has been reported to be higher in trials comparing AIs
      with tamoxifen; comparisons within the MA.17 trial, which evaluated an AI versus
      placebo, did not show increases in hypercholesterolaemia or in cardiovascular
      events with the AI. When treating breast cancer patients, oncologists should
      consider the same positive lifestyle changes that are proposed to lower the risk
      of cardiovascular disease in patients who do not have breast cancer. Moreover,
      physicians should assess cardiovascular risk, and monitor and treat patients
      already diagnosed with or at risk for coronary heart disease, according to
      established guidelines.

PMID- 16978037
TI  - Extended-release intramuscular naltrexone.
AB  - An extended-release intramuscular formulation of naltrexone that provides
      sustained release of the drug over a 28-day period has been developed with the
      aim of improving treatment adherence in patients treated with naltrexone for
      alcohol dependence. Biodegradable polylactide-co-glycolide polymer microspheres
      containing 34% w/w naltrexone are reconstituted in an aqueous suspension just
      prior to intramuscular administration. Extended-release intramuscular naltrexone
      380 mg administered once every 4 weeks, in combination with psychosocial therapy,
      demonstrated superior efficacy to placebo plus psychosocial therapy in reducing
      the heavy drinking event rate (primary endpoint) in adult patients with alcohol
      dependence in a 6-month well controlled trial. Among the subset of patients who
      abstained completely from drinking during the 7 days prior to the first dose of
      medication (n = 53; 8% of the total study population), those treated with
      extended-release intramuscular naltrexone 380 mg had greater reductions in the
      number of drinking days and the number of heavy drinking days compared with
      placebo recipients. Treatment with extended-release intramuscular naltrexone 380
      mg once every 4 weeks for up to 18 months was generally well tolerated, with
      infrequent treatment-related serious adverse events. The most common treatment
      emergent adverse events leading to treatment discontinuation were nausea,
      injection site reaction and headache. The proportion of patients with clinically
      significant plasma transaminase elevations was not different between patients
      receiving extended-release intramuscular naltrexone and those receiving placebo.

PMID- 16978038
TI  - Extended-release intramuscular naltrexone: a viewpoint by Henry R Kranzler.

PMID- 16978039
TI  - Extended-release intramuscular naltrexone: a viewpoint by Falk Kiefer.

PMID- 16978040
TI  - Extended-release intramuscular naltrexone: a viewpoint by Steven Siegel.

PMID- 16978043
TI  - Interaction of the halobacterial transducer to a halorhodopsin mutant engineered
      so as to bind the transducer: Cl- circulation within the extracellular channel.
AB  - An alkali-halophilic archaeum, Natronomonas pharaonis, contains two rhodopsins
      that are halorhodopsin (phR), a light-driven inward Cl- pump and phoborhodopsin
      (ppR), the receptor of negative phototaxis functioning by forming a signaling
      complex with a transducer, pHtrII (Sudo Y. et al., J. Mol. Biol. 357 [2006]
      1274). Previously, we reported that the phR double mutant, P240T/F250Y(phR), can
      bind with pHtrII. This mutant itself can transport Cl-, while the net transport
      was stopped upon formation of the complex. The flash-photolysis data were
      analyzed by a scheme in which phR --> 4 P1 --> P2 --> 4 P3 --> P4 --> phR. The P3
      of the wild-type and the double mutant contained two components, X- and O
      intermediates. After the complex formation, however, the P3 of the double mutant
      lacked the X-intermediate. These observations imply that the X-intermediate
      (probably the N-intermediate) is the state having Cl- in the cytoplasmic binding
      site and that the complex undergoes an extracellular Cl- circulation because of
      the inhibition of formation of the X-intermediate.

PMID- 16978041
TI  - Intravenous nicardipine: its use in the short-term treatment of hypertension and
      various other indications.
AB  - Nicardipine is a water soluble calcium channel antagonist, with predominantly
      vasodilatory actions. Intravenous (IV) nicardipine (Cardene IV), which
      demonstrates a relatively rapid onset/offset of action, is used in situations
      requiring the rapid control of blood pressure (BP). IV nicardipine was as
      effective as IV nitroprusside in the short-term reduction of BP in patients with
      severe or postoperative hypertension. A potential role for IV nicardipine in the
      intraoperative acute control of BP in patients undergoing various surgical
      procedures (including cardiovascular, neurovascular and abdominal surgery), and
      in the deliberate induction of reduced BP in surgical procedures in which
      haemostasis may be difficult (e.g. surgery involving the hip or spine) was
      demonstrated in preliminary studies. Preliminary studies also indicated the
      ability of a bolus dose of IV nicardipine to attenuate the hypertensive response,
      but not the increase in tachycardia, after laryngoscopy and tracheal intubation
      in anaesthetised patients. In large, well designed studies, IV nicardipine
      prevented cerebral vasospasm in patients with recent aneurysmal subarachnoid
      haemorrhage; however, overall clinical outcomes at 3 months were similar to those
      in patients who received standard management. Small preliminary studies have
      investigated the use of IV nicardipine in a variety of other settings, including
      acute intracerebral haemorrhage, acute ischaemic stroke, pre-eclampsia, acute
      aortic dissection, premature labour and electroconvulsive therapy.In conclusion,
      the efficacy of IV nicardipine in the short-term treatment of hypertension in
      settings for which oral therapy is not feasible or not desirable is well
      established. The ability to titrate IV nicardipine to the tolerance levels of
      individual patients makes this agent an attractive option, especially in
      critically ill patients or those undergoing surgery. Potential exists for further
      investigation of the use of this agent in clinical settings where a vasodilatory
      agent with minimal inotropic effects is appropriate.

PMID- 16978044
TI  - Application of fluorescence resonance energy transfer (FRET) to investigation of
      light-induced conformational changes of the phoborhodopsin/transducer complex.
AB  - The photoreceptor phoborhodopsin (ppR; also called sensory rhodopsin II) forms a
      complex with its cognate the Halobacterial transducer II (pHtrII) in the
      membrane, through which changes in the environmental light conditions are
      transmitted to the cytoplasm in Natronomonas pharaonis to evoke negative
      phototaxis. We have applied a fluorescence resonance energy transfer (FRET)-based
      method for investigation of the light-induced conformational changes of the
      ppR/pHtrII complex. Several far-red dyes were examined as possible fluorescence
      donors or acceptors because of the absence of the spectral overlap of these dyes
      with all the photointermediates of ppR. The flash-induced changes of distances
      between the donor and an acceptor linked to cysteine residues which were
      genetically introduced at given positions in pHtrII(1-159) and ppR were
      determined from FRET efficiency changes. The dye-labeled complex was studied as
      solubilized in 0.1% n-dodecyl-beta-D-maltoside (DDM). The FRET-derived changes in
      distances from V78 and A79 in pHtrII to V185 in ppR were consistent with the
      crystal structure data (Moukhametzianov, R. et al. [2006] Nature, 440, 115-119).
      The distance from D102 in pHtrII linker region to V185 in ppR increased by 0.33
      angstroms upon the flash excitation. These changes arose within 70 ms (the dead
      time of instrument) and decayed with a rate of 1.1 +/- 0.2 s. Thus, sub-angstrom
      scale distance changes in the ppR/pHtrII complex were detected with this FRET
      based method using far-red fluorescent dyes; this method should be a valuable
      tool to investigate conformation changes in the transducer, in particular its
      dynamics.

PMID- 16978045
TI  - Modeling of oxygen transport and cellular energetics explains observations on in
      vivo cardiac energy metabolism.
AB  - Observations on the relationship between cardiac work rate and the levels of
      energy metabolites adenosine triphosphate (ATP), adenosine diphosphate (ADP), and
      phosphocreatine (CrP) have not been satisfactorily explained by theoretical
      models of cardiac energy metabolism. Specifically, the in vivo stability of ATP,
      ADP, and CrP levels in response to changes in work and respiratory rate has
      eluded explanation. Here a previously developed model of mitochondrial oxidative
      phosphorylation, which was developed based on data obtained from isolated cardiac
      mitochondria, is integrated with a spatially distributed model of oxygen
      transport in the myocardium to analyze data obtained from several laboratories
      over the past two decades. The model includes the components of the respiratory
      chain, the F0F1-ATPase, adenine nucleotide translocase, and the mitochondrial
      phosphate transporter at the mitochondrial level; adenylate kinase, creatine
      kinase, and ATP consumption in the cytoplasm; and oxygen transport between
      capillaries, interstitial fluid, and cardiomyocytes. The integrated model is able
      to reproduce experimental observations on ATP, ADP, CrP, and inorganic phosphate
      levels in canine hearts over a range of workload and during coronary
      hypoperfusion and predicts that cytoplasmic inorganic phosphate level is a key
      regulator of the rate of mitochondrial respiration at workloads for which the
      rate of cardiac oxygen consumption is less than or equal to approximately 12
      mumol per minute per gram of tissue. At work rates corresponding to oxygen
      consumption higher than 12 mumol min(-1) g(-1), model predictions deviate from
      the experimental data, indicating that at high work rates, additional regulatory
      mechanisms that are not currently incorporated into the model may be important.
      Nevertheless, the integrated model explains metabolite levels observed at low to
      moderate workloads and the changes in metabolite levels and tissue oxygenation
      observed during graded hypoperfusion. These findings suggest that the observed
      stability of energy metabolites emerges as a property of a properly constructed
      model of cardiac substrate transport and mitochondrial metabolism. In addition,
      the validated model provides quantitative predictions of changes in phosphate
      metabolites during cardiac ischemia.

PMID- 16978046
TI  - Mathematical modeling identifies inhibitors of apoptosis as mediators of positive
      feedback and bistability.
AB  - The intrinsic, or mitochondrial, pathway of caspase activation is essential for
      apoptosis induction by various stimuli including cytotoxic stress. It depends on
      the cellular context, whether cytochrome c released from mitochondria induces
      caspase activation gradually or in an all-or-none fashion, and whether caspase
      activation irreversibly commits cells to apoptosis. By analyzing a quantitative
      kinetic model, we show that inhibition of caspase-3 (Casp3) and Casp9 by
      inhibitors of apoptosis (IAPs) results in an implicit positive feedback, since
      cleaved Casp3 augments its own activation by sequestering IAPs away from Casp9.
      We demonstrate that this positive feedback brings about bistability (i.e., all-or
      none behaviour), and that it cooperates with Casp3-mediated feedback cleavage of
      Casp9 to generate irreversibility in caspase activation. Our calculations also
      unravel how cell-specific protein expression brings about the observed
      qualitative differences in caspase activation (gradual versus all-or-none and
      reversible versus irreversible). Finally, known regulators of the pathway are
      shown to efficiently shift the apoptotic threshold stimulus, suggesting that the
      bistable caspase cascade computes multiple inputs into an all-or-none caspase
      output. As cellular inhibitory proteins (e.g., IAPs) frequently inhibit
      consecutive intermediates in cellular signaling cascades (e.g., Casp3 and Casp9),
      the feedback mechanism described in this paper is likely to be a widespread
      principle on how cells achieve ultrasensitivity, bistability, and
      irreversibility.

PMID- 16978047
TI  - Intricate knots in proteins: Function and evolution.
AB  - Our investigation of knotted structures in the Protein Data Bank reveals the most
      complicated knot discovered to date. We suggest that the occurrence of this knot
      in a human ubiquitin hydrolase might be related to the role of the enzyme in
      protein degradation. While knots are usually preserved among homologues, we also
      identify an exception in a transcarbamylase. This allows us to exemplify the
      function of knots in proteins and to suggest how they may have been created.

PMID- 16978049
TI  - The mesenchymal stem cell advantage.

PMID- 16978048
TI  - Transcriptional dynamics of the embryonic stem cell switch.
AB  - Recent ChIP experiments of human and mouse embryonic stem cells have elucidated
      the architecture of the transcriptional regulatory circuitry responsible for cell
      determination, which involves the transcription factors OCT4, SOX2, and NANOG. In
      addition to regulating each other through feedback loops, these genes also
      regulate downstream target genes involved in the maintenance and differentiation
      of embryonic stem cells. A search for the OCT4-SOX2-NANOG network motif in other
      species reveals that it is unique to mammals. With a kinetic modeling approach,
      we ascribe function to the observed OCT4-SOX2-NANOG network by making plausible
      assumptions about the interactions between the transcription factors at the gene
      promoter binding sites and RNA polymerase (RNAP), at each of the three genes as
      well as at the target genes. We identify a bistable switch in the network, which
      arises due to several positive feedback loops, and is switched on/off by input
      environmental signals. The switch stabilizes the expression levels of the three
      genes, and through their regulatory roles on the downstream target genes, leads
      to a binary decision: when OCT4, SOX2, and NANOG are expressed and the switch is
      on, the self-renewal genes are on and the differentiation genes are off. The
      opposite holds when the switch is off. The model is extremely robust to parameter
      changes. In addition to providing a self-consistent picture of the
      transcriptional circuit, the model generates several predictions. Increasing the
      binding strength of NANOG to OCT4 and SOX2, or increasing its basal
      transcriptional rate, leads to an irreversible bistable switch: the switch
      remains on even when the activating signal is removed. Hence, the stem cell can
      be manipulated to be self-renewing without the requirement of input signals. We
      also suggest tests that could discriminate between a variety of feedforward
      regulation architectures of the target genes by OCT4, SOX2, and NANOG.

PMID- 16978050
TI  - When genomes and stem cells meet: New perspectives for medical applications of
      stem cell research through the Australian/U.S. collaborative.

PMID- 16978051
TI  - Stressed stem cells: Temperature response in aged mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) derived from young (6 week) and aged (56 week)
      Wistar rats were cultured at standard (37 degrees C) and reduced (32 degrees C)
      temperature and compared for age markers and stress levels. (ROS, NO, TBARS,
      carbonyls, lipofuscin, SOD, GPx, apoptosis, proteasome activity) and heat shock
      proteins (HSP27, -60, -70, -90). Aged MSCs display many of the stress markers
      associated with aging in other cell types, but results vary across marker
      categories and are temperature dependant. In young MSCs, culturing at reduced
      temperature had a generally beneficial effect: the anti-apoptotic heat shock
      proteins HSP 27, HSP70, and HSP90 were up-regulated; pro-apoptotic HSP60 was
      downregulated; SOD, GPx increased; and levels in ROS, NO, TBARS, carbonyl, and
      lipofuscin were diminished. Apoptosis was reduced, but also proteasome activity.
      In contrast, in aged MSCs, culturing at reduced temperature generally produced no
      'beneficial' changes in these parameters, and can even have detrimental effects.
      Implications for tissue engineering and for stem cell gerontology are discussed.
      The results suggest that a 'hormesis' theory of stress response can be extended
      to MSCs, but that cooling cultivation temperature stress produces positive
      effects in young cells only.

PMID- 16978052
TI  - From the atom to the cell: Is the cat alive? Quantum mechanics and stem cell
      plasticity as deja vu.
AB  - The concepts submitted by quantum mechanics fascinated the scientific community
      during the first half of the 20(th) century. The second half was dominated by
      biology, culminating in the sequencing of the human genome and the study of stem
      cells. Although the anticipated revolution of cellular therapies in medicine is
      in its infancy, the conceptual debate over stem cell plasticity shares
      similarities with evolution of the quantum theory. Are there notions and modes of
      thinking that stem cell biologists should adopt from the evolution in the
      interpretation of the laws of physics?

PMID- 16978053
TI  - Mired in the quagmire of uncertainty: The "catch-22" of embryonic stem cell
      research.
AB  - Pluripotent human embryonic stem (ES) cells hold remarkable therapeutic
      potential, but their use is fraught with moral, ethical, scientific, and
      political concerns. In this essay, I discuss how an odd combination of patent
      issues, presidential policy, market uncertainties, and evolving Food and Drug
      Administration regulations have together hindered the progress of ES cell
      research in the United States of America. This coalescence of issues is unique. I
      suggest that these factors explain why the United States has not been a dominant
      player in advancing ES research. I predict that small, noncontroversial changes
      would go far in ameliorating many of the roadblocks that now exist. Most of these
      changes would not require a change in policy or even action by the U.S.
      government; a simple clarification and definition would suffice. The reason these
      changes have met solid resistance is suggested to derive from financial rather
      than moral, ethical, or scientific issues.

PMID- 16978054
TI  - Cord blood mesenchymal stem cells: Potential use in neurological disorders.
AB  - Our previous studies demonstrate enhanced neural protective effects of cord blood
      (CB) cells in comparison to stem cells from adult marrow. To determine further
      whether mesenchymal stem cells (MSCs) derived from human umbilical cord blood
      (hUCB) possess optimal characteristics for neural therapy, we isolated
      populations of plastic-adherent CB MSCs. These cells generated CD34-, CD45-,
      CD11b-, CD3-, CD19- cells in culture and failed to produce CFU-M, CFU-GEMM, or
      CFU-GM hematopoietic colonies in methylcellulose. However, cultured CB MSCs
      possessed a remarkable ability to support proliferation as well as
      differentiation of hematopoietic cells in vitro. In addition, supernatants from
      cultured CB MSCs promoted survival of NT2 N neural cells and peripheral blood
      mononuclear cells (MNCs) cultured under conditions designed to induce cell stress
      and limit protein synthesis. After incubation in neural differentiation medium,
      CB MSCs expressed the neural cell-surface antigen A2B5, the neurofilament
      polypeptide NF200, the oligodendrocyte precursor marker 04, intermediate filament
      proteins characteristic of neural differentiation (nestin and vimentin), as well
      as the astrocyte marker glial fibrillary acidic protein (GFAP) and the neural
      progenitor marker TUJ-1. We examined the immunomodulatory effects of the CB MSCs
      after co-culture with murine splenocytes. Whereas spleen cells from normal
      C57Bl/6 mice exhibited a prominent immunoglobulin M (IgM) response after
      immunization with the T cell-dependent antigen sheep red blood cells, this
      response was significantly decreased after incubation with CB MSCs. These data
      indicate that CB MSCs possess multiple utilities that may contribute to their
      therapeutic potency in the treatment of neurological disorders.

PMID- 16978055
TI  - Multipotent adult progenitor cell lines originating from the peripheral blood of
      green fluorescent protein transgenic swine.
AB  - Multipotent self-renewing stem cell lines have been established using peripheral
      blood mononuclear cells from adult green fluorescent protein transgenic swine.
      These cells proliferate as nonadherent spheroids in primordial-specific culture
      media and readily differentiate into angiogenic, osteogenic, adipogenic, and
      neurogenic phenotypes when cultured under the appropriate conditions. These cells
      are designated peripheral blood-derived multipotent adult progenitor cells (PBD
      MAPCs). When differentiated in endothelial-specific media, these cells exhibit a
      cobblestone morphology and express von Willebrand factor (vWF), take up 1,1'
      dioctadecyl-3,3,3',3'-tetramethyl-indocarboxyanine-labeled acetylated low-density
      lipoprotein DiI-Ac-LDL, and form tubes with lumens when grown on pads of
      Matrigel. Under different culture conditions, the cells appear whorl-like in
      appearance and express alpha-actin, indicative of smooth muscle phenotype. In the
      presence of dexamethasone and ascorbic acid, PBD-MAPCs differentiate into cells
      that produce Alizarin Red-staining extracellular mineral, consistent with an
      osteogenic potential. Under different conditions the cells produce Oil Red O
      staining lipid vacuoles, suggestive of an adipocyte phenotype. We have also
      developed conditions that induce PBDMAPCs to differentiate into neural cells,
      confirmed by the expression of specific neuron- and glial-specific markers. Upon
      transplantation into rat brain, the neurogenic cells survive and migrate
      throughout the striatum and corpus callosum. The cells remain brightly
      fluorescent throughout their time in culture, during in vitro differentiation,
      and after in vivo transplantation. PBD-MAPCs have been maintained in primordial
      cell media for more than 100 doublings, yet can be induced to differentiate
      rapidly and efficiently into distinct cell types. PBD-MAPCs are ideal tools to
      study the mechanisms of differentiation and may be superior to embryonic stem
      cells as cellular therapeutics.

PMID- 16978056
TI  - Horse embryonic stem cell lines from the proliferation of inner cell mass cells.
AB  - Inner cell mass (ICM) cells were isolated immunosurgically from day 7-8 horse
      blastocysts and, after proliferation in vitro for 15-28 passages, three lines of
      cells were confirmed to be embryonic stem (ES) cells by their continued
      expression of alkaline phosphatase activity and their ability to bind antisera
      specific for the recognized stem cell markers, SSEA-1, TRA-1-60, TRA-1-81, and
      the key embryonic gene Oct-4. When maintained under feeder cell-free conditions
      in vitro, the three lines of cells differentiated into cells of ectodermal,
      endodermal, and mesodermal lineages. However, they did not form teratomata when
      injected into the testes of severe combined immunodeficiency (SCID)/beige
      immunoincompetent mice, thereby indicating a significant difference in phenotype
      between ES cells of the horse and those of the mouse and human.

PMID- 16978057
TI  - Characterization and gene expression profiling of five new human embryonic stem
      cell lines derived in Taiwan.
AB  - Many human embryonic stem cell (hESC) lines have been reported, but only a few of
      them have been fully characterized. In this report, five new hESC lines were
      derived from 32 discarded blastocysts in Taiwan, and these lines were
      continuously cultured on mitotically inactivated mouse embryonic fibroblast (MEF)
      feeder layer in the hESC medium for more than 44 passages and underwent
      freezing/thawing processes. All five hESC lines expressed characteristic
      undifferentiated hESC markers, such as SSEA-4, TRA-1-81, alkaline phosphatase,
      TERT, and the transcription factors POU5F1 (OCT4) and NANOG. hESC lines T1 and T3
      possess normal female karyotypes, whereas lines T4 and T5 are normal male, but
      line T2 is male trisomy 12 (47XY,+12). hESC lines T1, T2, T3, and T5 were able to
      produce teratomas in severe combined immunodeficient (SCID) mice, and line T4
      could only form embryoid bodies (EBs) in vitro. Global gene expression profiles
      of these five newly derived hESC lines were analyzed using the Affymetrix human
      genome U133 plus 2.0 GeneChip. The results showed that 4,145 transcripts,
      including 19% of unknown functions, were detected in all five hESC lines.
      Comparison of the 4,145 genes commonly expressed in the five hESC lines with
      those genes expressed in teratomas produced by the hESC line T1 and placenta
      revealed 40 genes exclusively expressed in all five hESC lines. These 40 genes
      include the previously reported stemness genes, such as POU5F1 (OCT4), NANOG,
      TDGF1 (CRIPTO), SALL4, LECT1, and BUB1 responsible for self-renewal and
      pluripotent differentiation. The global gene expression analysis also indicated
      that the transforming growth factor-beta (TGF-beta)/activin branch components
      inhibin BC, ACVR2A, ACVR1 (ALK2), TGFBR1 (ALK5), and SMAD2 were found to be
      highly expressed in undifferentiated states of these five hESC lines and
      decreased upon differentiation. In short, the hESC nature of these five hESC
      lines is supported by the undifferentiated state, extensive renewal capacity, and
      pluripotency, including the ability to form teratomas and/or EBs. These cell
      lines will be useful for human embryonic stem cell biology and drug development.

PMID- 16978058
TI  - Long-term culture of human gingival keratinocyte progenitor cells by down
      regulation of 14-3-3 sigma.
AB  - Human gingival keratinocytes in culture stop proliferating after a limited number
      of passages. This limitation is associated with a gradual depletion of the stem
      cell compartment of the cell population. Human skin keratinocytes have a three-
      to five-fold higher proliferation capacity under similar culture conditions, and
      previous studies indicated that stable down-regulation of the 14-3-3 sigma
      protein in these cultures prevents stem cell differentiation and generates
      immortal cell lines without the effects of tumorigenic transformation, e.g.,
      genotypic alterations. In this report, we demonstrate the creation of an
      immortalized human gingival keratinocyte stem cell line by stable down-regulation
      of the 14-3-3 sigma protein. Keratinocyte cultures were generated from human
      subjects ranging from 17 to 92 years of age and retrovirally transduced with a 14
      3-3 sigma antisense RNA expression construct. In contrast to the control
      cultures, which propagated for only 2-5 passages and 25-35 cell doublings, the 14
      3-3 sigma-transduced cultures propagated for 11 passages and 110 cell doublings
      so far. The percentage of stem cells measured by clonal analysis, which gradually
      decreased in the control cultures, increased to a steady level of over 90% in the
      14-3-3 sigma down-regulated culture. This gingival keratinocyte stem cell line
      and others, which can be generated using the same procedure, have the potential
      to be useful for studies on stem cell differentiation, for developing gene
      therapy procedures that target the gingival epithelium, as well as a stable
      platform for testing oral hygiene products and as potential material for
      preprosthetic surgery.

PMID- 16978059
TI  - Molecular cloning and function of Oct-3 isoforms in cynomolgus monkey embryonic
      stem cells.
AB  - Oct-3 is a key molecule for maintaining self-renewal in mouse embryonic stem (ES)
      cells. The function of Oct-3 in ES cells of other species, however, especially
      primate ES cells, is not clear. In the present study, we cloned two splicing
      isoforms of Oct-3, Oct-3A and Oct-3B, from cynomolgus monkey ES cells, and found
      that they have high homology to human Oct-3A and Oct-3B. To examine their
      function, Oct-3A and Oct-3B were overexpressed in cynomolgus monkey ES cells.
      Transient Oct-3A overexpression induced ES cell differentiation into endodermal
      and mesodermal lineages and disrupted proliferation of undifferentiated monkey ES
      cells. In contrast, Oct-3B overexpression did not induce differentiation of
      monkey ES cells. These findings indicate that a certain Oct-3A expression level
      has an important role in sustaining self-renewal in non-human primate ES cells.

PMID- 16978060
TI  - Enriched NCAM-positive cells form functional dopaminergic neurons in the rat
      model of Parkinson's disease.
AB  - We describe a method of generating an enriched population of NCAM-positive cells
      from a human teratocarcinoma cell line (NTera2/D1) and their differentiation into
      midbrain dopaminergic neurons in the absence of the caudalizing factor retinoic
      acid (RA). NTera2 cells were induced to form embryoid bodies and then to generate
      nestin-positive cells on treatment with serum-free defined medium supplemented
      with neurotrophic factors. We enriched the neuroprogenitor population by magnetic
      sorting of the nestin-positive cells using the antibody to neural cell adhesion
      molecule (NCAM). These cells were expanded by exposing them to the signaling
      molecule sonic hedgehog (SHH) in conjunction with fibroblast growth factor-8 (FGF
      8). The predifferentiated cells when analyzed by RT-PCR showed expression of
      dopaminergic markers such as Nurr1, Engrailed-1, aromatic amino decarboxylase
      (AADC), VMAT2, tyrosine hydroxylase (TH), and dopamine transporter (DAT). These
      cells also stained positively for protein markers such as nestin, NCAM, MAP-2,
      and TH. We further demonstrated that when transplanted into the brain of
      Parkinsonian rats, these neuroprogenitor cells did not form tumors but
      differentiated into dopaminergic neurons, as revealed by TH immunolabeling. The
      origin of transplanted cells were further confirmed by positive immunolabeling
      with anti-human nuclei. Our results suggest that enriching the neuroprogenitor
      population by magnetic sorting prevents tumor formation and is a prerequisite
      before cell replacement therapy for Parkinson's disease.

PMID- 16978061
TI  - Autologous adipose tissue-derived stromal cells for treatment of spinal cord
      injury.
AB  - Isolated rat adipose tissue-derived stromal cells (rATSCs) contain pluripotent
      cells that can be differentiated into a variety of cell lineages, including
      neural cells. Recent work has shown that ATSCs can make neurosphere-like clumps
      and differentiate into neuron-like cells expressing neuronal markers, but their
      therapeutic effect is unclear. Here we report that intravenous infusion of
      oligodendrocyte precursor cells (OPCs) derived from rATSC autograft cells sources
      improve motor function in rat models of spinal cord injury (SCI). After 4-5
      weeks, transplanted rATSC-OPC cells survived and migrated into the injured region
      of SCI very efficiently (30-35%) and migrated cells were partially differentiated
      into neurons and oligodendrocyte. Also, we found some of the engrafted OPCs
      migrated and integrated in the kidney, brain, lung, and liver through the
      intravenous system. Behavioral analysis revealed the locomotor functions of OPC
      autografted SCI rats were significantly restored. Efficient migration of
      intravenously engrafted rATSC-OPCs cells into SCI lesion suggests that SCI
      induced chemotaxic factors facilitate migration of rATSC-OPCs. Here, we verified
      that engrafted rATSCs and SCI-induced chemotaxic factors indeed play an important
      role in proliferation, migration, and differentiation of endogeneous spinal cord
      derived neural progenitor cells in the injured region. In transplantation
      paradigms, the interaction between engrafted rATSC-OPCs and endogeneous spinal
      cord-derived neuronal progenitor cells will be important in promoting healing
      through fate decisions, resulting in coordinated induction of cell migration and
      differentiation.

PMID- 16978063
TI  - PU.1: An ETS family transcription factor that regulates leukemogenesis besides
      normal hematopoiesis.
AB  - The hematopoietic transcription factor PU.1, which is required for lymphomyeloid
      differentiation of stem cells, was originally identified as an oncogene. In
      erythroid progenitors, the integration of spleen focus-forming virus (SFFV) into
      the PU.1 locus causes its overexpression, which blocks their terminal
      differentiation into erythrocytes and ultimately leads to the development of
      erythroleukemia. However, in myeloid lineages, PU.1 promotes granulocytic and
      monocytic differentiation, and graded reduction in its expression blocks their
      differentiation or maturation and thereby causes myelogenous leukemia. Thus, in
      addition to normal hematopoietic regulation, PU.1 plays a significant role in
      leukemogenesis. In the following review, we have consolidated our understanding
      of the role of transcription factor PU.1 in the development of erythroid as well
      myeloid leukemia.

PMID- 16978062
TI  - Dental follicle progenitor cell heterogeneity in the developing mouse
      periodontium.
AB  - As a developmental precursor for diverse periodontal tissues, the dental follicle
      (DF) harbors great promise for periodontal tissue regeneration. However,
      development of optimal therapy awaits the answer to a key question that impinges
      on many issues in development-Do adult progenitor tissues form a homogeneous cell
      population that differentiates into target tissues when they arrive at the site,
      or they contain heterogeneous cell populations that are committed to specific
      fates? To address the homogeneity/heterogeneity question, we analyzed
      differentiation pathways and markers in several cloned DF cell lines. Our studies
      revealed that each of our cloned DF lines featured remarkably unique
      characteristics, indicative of a separate and distinct lineage. One line, DF1,
      was high in proliferative activity but did not display any mineralization
      behavior, suggesting that it might be related to a periodontal ligament-type
      lineage. DF2 was similar to DF1, but featured remarkably high alkaline
      phosphatase activity indicative of a highly undifferentiated state. DF3 matched
      the mineralization characteristics of a same stage alveolar bone line AB1 in
      terms of gene expression and von Kossa staining, indicating that DF3 might be of
      cementoblastic or alveolar bone osteoblastic lineage. To verify the multilineage
      potential of the DF for purposes of tissue engineering, a series of
      differentiation induction experiments was conducted. For identification purposes,
      characteristics of these heterogeneous follicular progenitor cells were compared
      with follicle components in tissue sections of the postnatal developing
      periodontium. The presence of heterogeneous cell populations in the DF mirrors
      individual developmental pathways in the formation of the dental integument. The
      profound cellular heterogeneity of the DF as an adult progenitor for tissue
      regeneration also suggests that heterogeneous cellular constituents might play as
      much of a role in tissue regeneration as the inducible characteristics of
      individual lineages might do.

PMID- 16978064
TI  - Review: novel nonviral delivery approaches for interleukin-12 protein and gene
      systems: curbing toxicity and enhancing adjuvant activity.
AB  - It has become increasingly apparent that the ability to generate an optimal host
      immune response requires effective cross talk between the innate and adaptive
      components of the immune system. Pro-inflammatory cytokines, in particular those
      that can induce a danger signal, often called signal 3, are crucial in this role
      of initiating and augmenting the presentation of exogenous antigen to T cells by
      dendritic cells. Interleukin-12 (IL-12) in particular has been defined as a
      "signal 3" cytokine required for the antigen cross priming. Given this unique
      interactive function, a significant amount of work has been performed to define
      possible therapeutic applications for IL-12. Systemic IL-12 administration can
      clearly act as a potent adjuvant for postvaccination T cell responses in a
      variety of diseases. As an example, in the cancer setting, systemic IL-12 is
      capable of suppressing tumor growth, metastasis, and angiogenesis in vivo. IL-12,
      however, has been associated with significant dose- and schedule-dependent
      toxicity in early clinical trials, results that have proven to be a major
      obstacle to its clinical application. Recent research has focused on decreasing
      the toxicity of IL-12 using different delivery approaches, including virus-based
      and gene-modified cell-based delivery. Although effective, these approaches also
      have limitations, including the generation of neutralizing antibodies, in
      addition to lacking the simplicity and versatility required for universal
      clinical application. Thus, there is a significant interest in the development of
      alternative delivery approaches for IL-12 administration that can overcome these
      issues. Several nonviral delivery approaches for IL-12 protein or gene expression
      vectors are being defined, including alum, liposomes, and polymer-based delivery.
      These developing approaches have shown promising adjuvant effects with
      significantly lessened systemic toxicity. This article discusses the potential
      capabilities of these nonvirus-based IL-12 delivery systems in different disease
      settings, including allergy, infection, and cancer.

PMID- 16978065
TI  - Cystic fibrosis and normal human airway epithelial cell response to influenza a
      viral infection.
AB  - Viral infections produce severe respiratory morbidity in children with cystic
      fibrosis (CF). CF cells are more susceptible to virus in part because of impaired
      airway epithelial activation of signal transducer and activator of transcription
      1 (Stat1). As Stat1 is a fundamental regulator of antiviral defenses, we
      hypothesized that there may be multiple alterations in the antiviral defense of
      CF epithelium compared with normal (NL). To obtain a comprehensive view of
      mucosal host responses to influenza and characterize the difference between CF
      and NL responses to influenza, gene expression profiles of primary human airway
      epithelial cells (HAEC) were evaluated using an interferon (IFN)-stimulated
      genes/AU/double-stranded RNA (dsRNA) microarray or quantitative real-time
      polymerase chain reaction (PCR) following influenza A infection. Gene expression
      was significantly modified by influenza in NL (228 genes) and CF (101 genes),
      with a similar pattern of gene response but with overall less numbers of
      responsive genes in CF (p < 0.05). Moreover, CF cells had less IFN-related
      antiviral gene induction at 24 h but greater inflammatory cytokine gene induction
      at 1 h after infection. Taken together, the lesser antiviral and greater early
      inflammatory response likely contribute to the severe respiratory illness of CF
      patients with viral infections.

PMID- 16978066
TI  - Cytokine gene expression profiles in human lymphocytes induced by a formula of
      traditional Chinese medicine, vigconic VI-28.
AB  - VI-28 is a formula of traditional Chinese medicine (TCM) that has been used in
      aged individuals to improve health and, recently, to treat patients with chronic
      human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections. The
      mechanism underlying its clinical effect is, however, largely unknown. In the
      current study, we used a transwell culture system that mimics the in vivo
      situation and applied microarray technology to explore the effect of VI-28 on
      gene expression in human lymphocytes. The VI-28 treatment induced expression of a
      number of proinflammatory cytokines/chemokines in both peripheral blood
      mononuclear cells (PBMC) and spleen cells, including interleukin-1 (IL-1), growth
      related protein-beta (GRO-beta) and epithelial cellderived neutrophil-activating
      peptide (ENA-78 [CXCL5]). Furthermore, a specific upregulation of interferon-
      gamma (IFN-gamma), monokine induced by gamma interferon (MIG [CXCL9]) and
      interleukin-2 receptor alpha (IL-2Ralpha) in spleen cells was noted, whereas
      tissue inhibitor of metalloproteinase-3 (TIMP-3) and disabled-2 (DAB2) were
      downregulated. VI-28 might, thus, enhance both innate and acquired immunity, in
      particular, T cell function. In addition, genes with no obvious immunologic
      function, such as insulin-like growth factor-2 (IGF- 1) and CD9, were also
      differentially affected. Further analysis of individual and combination of
      ingredients of VI-28 may shed light on the role of this herbal medicine in
      combating different diseases.

PMID- 16978067
TI  - IL-18 expression in pigs following infection with Mycoplasma hyopneumoniae.
AB  - Little is known about the detail of the immune response during infection of pigs
      with Mycoplasma hyopneumoniae (Mhp). To further understand this important porcine
      pathogen, we examined the interleukin-18 (IL- 18) response in experimentally
      infected piglets. We found that large amounts of IL-18 were produced in the
      bronchoalveolar lavage fluids (BALF) of pigs experimentally infected with Mhp.
      However, the concentration of interferon-gamma (IFN-gamma) in the same BALF was
      negatively correlated with that of IL-18. The antibody response against Mhp was
      found to be associated with the IL-18 concentration in the BALF.
      Immunohistochemical staining revealed that both IL-18 and IL-18 receptor alpha
      chain (IL-18Ralpha) were present in macrophages and plasma cells in the lungs of
      Mhp-infected pigs. Lung mononuclear cells isolated from pneumonic lesions
      secreted IL-18 and prostaglandin E(2) (PGE(2)) in vitro, and PGE(2) production
      was enhanced by stimulation with IL-18. These results indicate that IL-18
      produced in the pig lung contributes to the development of innate and acquired
      immune responses against Mhp as a proinflammatory cytokine rather than as an IFN
      gamma-inducing factor and may be involved in immunomodulation in pigs.

PMID- 16978068
TI  - The circadian gene mPer2 regulates the daily rhythm of IFN-gamma.
AB  - Circadian and daily rhythms regulate many aspects of physiology and behavior.
      Although a growing number of studies suggest that circadian disruptions may
      render organisms more susceptible to infection and cancer, the molecular links
      between the circadian system and the immune system are largely unknown. Here we
      report that mice carrying a loss-of-function mutation in the Per2 gene, a key
      component of the molecular circadian clock, lacked the physiologic daily rhythm
      of interferon-gamma (IFN-gamma) mRNA and protein expression in the spleen. These
      observations were associated with a significant alteration in the expression of
      canonical clock genes. In addition, Per2 mutant mice failed to show a daily
      rhythm in IFN-gamma serum levels, which were significantly lower than those
      determined in wild-type mice during the early light period. These findings
      provide novel evidence for a direct circadian regulation of IFN-gamma, a critical
      cytokine modulating the immune response.

PMID- 16978069
TI  - Interferon-induced, antiviral human MxA protein localizes to a distinct
      subcompartment of the smooth endoplasmic reticulum.
AB  - Human MxA protein belongs to the superfamily of dynamin-like large GTPases that
      are involved in intracellular membrane trafficking. MxA is induced by interferons
      alpha/beta (IFN-alpha/beta) and is a key component of the antiviral response
      against RNA viruses. Here, we show that MxA localizes to membranes that are
      positive for specific markers of the smooth endoplasmic reticulum, such as
      Syntaxin17, but is excluded from other membrane compartments. Overexpression of
      MxA leads to a characteristic reorganization of the associated membranes.
      Interestingly, Hook3, mannose-6-phosphate receptor, and Lamp-1, which normally
      accumulate in cis- Golgi, endosomes, and lysosomes, respectively, also
      colocalized with MxA, indicating that these markers were redistributed to the MxA
      positive compartment. Functional assays, however, did not show any effect of MxA
      on endocytosis or the secretory pathway. The present results demonstrate that MxA
      is an IFN-induced antiviral effector protein that resembles the constitutively
      expressed large GTPase family members in its capacity to localize to and
      reorganize intracellular membranes.

PMID- 16978070
TI  - Etanercept reduces late endotoxin-induced pulmonary hypertension in the pig.
AB  - To evaluate whether etanercept, a tumor necrosis factor (TNF)-blocking agent, may
      counteract hemodynamic deterioration in endotoxemic shock, we designed a
      prospective, randomized placebo-controlled trial with parallel groups, consisting
      of 13 pigs aged 10-14 weeks receiving general anesthesia. Five pigs were given 25
      mg of etanercept, 1 h before the start of a 4-h continuous infusion of endotoxin.
      Another 5 pigs were given the corresponding volume of saline, 1 h before the
      start of a 4-h continuous infusion of endotoxin. Three pigs were given 25 mg of
      etanercept, 1 hr before the start of a 4-h continuous infusion of saline. At 1 h
      of endotoxemia, mean pulmonary arterial pressure (MPAP) and pulmonary vascular
      resistance index (PVRI) increased identically in both groups of pigs receiving
      endotoxin. Thereafter, two distinct different patterns in hemodynamics were
      observed. TNF-blocked pigs showed significantly lower MPAP and PVRI compared to
      controls. In the etanercept-treated endotoxemic pigs, Doppler analysis of the
      diastolic mitral inflow demonstrated a significantly increased E/A-ratio (early
      mitral wave inflow was divided by the atrial wave) at 2 h. The TNFblocking agent
      etanercept normalized two hemodynamic features of endotoxin-induced septic shock
      in pigs: (1) the sustained pulmonary hypertension and (2) diastolic dysfunction.

PMID- 16978071
TI  - Blood leukocyte mRNA expression for IL-10, IL-1Ra, and IL-8, but not IL-6,
      increases after exercise.
AB  - The primary purpose of this project was to study exercise-induced leukocyte
      cytokine mRNA expression. Changes in plasma cytokine levels and blood leukocyte
      mRNA expression for interleukin-6 (IL-6), IL-8, IL- 10, and IL-1 receptor
      antagonist (IL-1Ra) were measured in 12 athletes following 2 h of intensive
      cycling ( approximately 64% Watts(max)) while ingesting a carbohydrate or placebo
      beverage (randomized and double blinded). Blood samples were collected 30 min
      preexercise and immediately and 1 h postexercise. Carbohydate compared with
      placebo ingestion attenuated exercise-induced changes in plasma cortisol (8.8%
      vs. 62%, respectively), epinephrine (-9.2% vs. 138%), IL-6 (10-fold vs. 40-fold),
      IL-10 (8.9-fold vs. 26-fold, and IL-1Ra (2.1-fold vs. 5.6-fold). Significant time
      effects were measured for blood leukocyte IL-8 (2.4-fold increase 1 h
      postexercise), IL-10 (2.7-fold increase), IL-1Ra (2.2-fold increase), and IL-6
      (0.8-fold decrease) mRNA content, with no significant differences between Cho and
      Pla test conditions. In summary, gene expression for IL-8, IL-10, and IL-1Ra, but
      not IL-6, is increased in blood leukocytes taken from athletes following 2 h of
      intensive cycling and is not influenced by carbohydrate compared with placebo
      ingestion. mRNA expression was high enough to indicate a substantial contribution
      of blood leukocytes to plasma levels of IL-8, IL-10, and IL-1Ra during prolonged
      exercise.

PMID- 16978072
TI  - Evidence for the immunostimulatory effects of low-dose orally delivered human IFN
      alpha in cattle.
AB  - Orally delivered interferon-alpha (IFN-alpha) has been associated with systemic
      protection against various disorders in humans and animals. In an attempt to
      understand how IFN-alpha delivers a systemic signal following its local oral
      administration, the present study aimed at identifying genes differentially
      regulated in bovine peripheral blood through the use of cDNA microarrays
      following oral therapy with IFN-alpha. We identified thousands of genes to be IFN
      alpha regulated. Of these, about 8.5% had a minimum 4-fold degree of change, the
      majority of which represented novel IFN-stimulated genes (ISG). Several
      upregulated ISGs were transcripts with key and diverse biologic functions,
      including antigen processing and presentation, leukocyte migration, lymphocyte
      activation, immune effector and modulation functions, apoptosis, and
      hematopoiesis. Interestingly, IFN-alpha expression itself was not modulated in
      bovine peripheral blood, suggesting that the blood levels of IFN-alpha are not
      the hallmark of the immunostimulatory effects of oral IFN-alpha therapy. Rather,
      IFN-alpha seems to interact with local mucosal lymphoid cells in the
      gastrointestinal tract. This interaction may initiate a signaling cascade
      eventually leading to the transcriptional induction of ISGs, which in turn encode
      immunostimulatoiry proteins. Thus, ISGs, through the proteins they encode, may
      potentially perform critical immune modulation functions.

PMID- 16978073
TI  - Differential sensitivity of C57BL/6 (M-1) and BALB/c (M-2) macrophages to the
      stimuli of IFN-gamma/LPS for the production of NO: correlation with iNOS mRNA and
      protein expression.
AB  - C57BL/6 and BALB/c mice are prototype hosts for the study of resistance and
      susceptibility to several infectious diseases. In many cases, resistance of
      C57BL/6 is due to the microbicidal effect of nitric oxide (NO) produced by
      macrophages in response to interferon-gamma (IFN-gamma) and tumor necrosis factor
      alpha (TNF-alpha), mainly secreted by Th1 cells and macrophages, respectively.
      BALB/c, usually unable to give rise to Th1 lymphocytes, does not control certain
      infections. However, we and others have previously observed that regardless of
      the adaptive immune response, C57BL/6 (M-1) macrophages are far more sensitive to
      the stimulus of IFN-gamma-plus lipopolysaccharide (LPS) for the production of NO
      than are BALB/c (M-2) cells, a feature that might also account for resistance.
      Here, we report that the differential production of NO by M-1 and M-2 macrophages
      correlates with the accumulation of inducible nitric oxide synthase (iNOS) mRNA
      and protein, which shows that expression of iNOS is differentially regulated in M
      1 and M-2 cells. The higher accumulation of iNOS mRNA in M-1 cells is independent
      of its stability, and, thus, it is possible that transcription of the iNOS gene
      in these cells may be more efficient than in M-2 cells. A remarkable finding is
      that the level of iNOS protein is much higher in M-1 macrophages than in M-2
      cells, as compared with the mRNA levels, which makes us speculate that
      differential translational or posttranslational controls of iNOS gene are
      operative.

PMID- 16978075
TI  - Breaking with tradition: evidence-based antibiotic prophylaxis of open fractures.

PMID- 16978076
TI  - Can the clinical pulmonary infection score impact ICU antibiotic days?
AB  - BACKGROUND: The Clinical Pulmonary Infection Score (CPIS) has been used in the
      intensive care unit (ICU) as a decision tool for initiation of antibiotics in
      suspected pneumonia and also for discontinuing antibiotics if the CPIS score is
      <or=6 on day three of therapy, but it is not in common clinical use. We sought to
      determine if application of a CPIS score<or=6 at three days could reduce
      antibiotic use and if a blinded committee would have a greater percentage of
      patients with CPIS>6 on day one receiving antibiotics empirically for pneumonia.
      METHODS: Over 11 months, we evaluated empiric antibiotics prospectively in two
      ICUs of a large tertiary university teaching hospital. A pneumonia committee (PC)
      reviewed all patients and defined pneumonia according to the guidelines of the
      U.S. Centers for Disease Control and Prevention (CDC). The CPIS was calculated
      for all patients at day one and day three of antibiotic therapy. The percentage
      of patients with a CPIS<or=6 was compared for the ICU and PC, and the total
      antibiotic days potentially saved by using CPIS<or=6 as the criterion for
      treatment were determined. Receiver operating characteristic (ROC) curves and
      inter-observer reliability were determined. RESULTS: Three hundred twelve
      patients received empiric antibiotics, 83 of whom were believed to have pneumonia
      by the ICU staff (2,283 antibiotic days). On day one, the 55 patients started on
      antibiotics had a CPIS<or=6, with 1,460 antibiotic-days, and only 28 patients had
      a CPIS>6 (823 antibiotic-days). In contrast, the PC determined 19 patients (23%)
      to have pneumonia by the CDC definition (731 antibiotic-days), with eight of
      these patients having a CPIS<or=6 and 11 a CPIS>6. Pneumonia committee review
      resulted in fewer patients believed to have pneumonia and a greater percentage
      with a CPIS>6 (odds ratio [OR] 2.7; 95% confidence interval [CI] 0.86, 8.6;
      p=0.05). Restriction of antibiotics to patients with a CPIS>6 would have saved
      1,460 antibiotic-days at day one and 1,053 days if treatment was delayed until
      day three. Clinical Pulmonary Infection Score ROC curves for the PC showed an
      area under the curve (AUC) of 0.82 (95% CI 0.72, 0.91), whereas the AUC for the
      ICU group was 0.85 (95% CI 0.79, 0.92). The sensitivity and specificity of a
      CPIS>6 for the PC were 79% and 75%, respectively, with correct prediction 76% of
      the time. The inter-observer reliability of the CPIS had a kappa value of 0.88.
      CONCLUSIONS: This prospective evaluation confirms that 50% of antibiotic-days in
      our ICU are used empirically for pneumonia when that infection is not likely to
      be present by either CDC or CPIS criteria. Although the CPIS has good reliability
      and acceptable sensitivity and specificity, PC review and CPIS<or=6 were commonly
      divergent (42-47%). Thus, better strategies should be developed for
      identification of pneumonia and empiric antibiotic administration in the ICU.

PMID- 16978077
TI  - Comparison of sequential intravenous/oral ciprofloxacin plus metronidazole with
      intravenous ceftriaxone plus metronidazole for treatment of complicated intra
      abdominal infections.
AB  - BACKGROUND AND PURPOSE: Intra-abdominal infections are a substantial clinical
      problem and an important cause of morbidity and death in the hospital. Optimal
      treatment requires both source control and antibiotic therapy. Sequential
      intravenous (IV) to oral therapy may improve patient convenience and reduce total
      health care costs. In this randomized, double-blind trial, the efficacy of
      sequential IV-to-oral ciprofloxacin plus metronidazole was compared with
      ceftriaxone plus metronidazole in adult patients with complicated intra-abdominal
      infections. METHODS: The trial enrolled 531 patients, who began with IV therapy.
      Patients who improved clinically were switched to oral therapy on day three or
      later. The clinical and bacteriological responses four to six weeks after the end
      of therapy and the safety of the two regimens were assessed. To maintain
      blinding, the patients received placebo IV in the ciprofloxacin group or placebo
      orally in the ceftriaxone group. A total of 475 patients (235 ciprofloxacin plus
      metronidazole, 240 ceftriaxone plus metronidazole) were valid for evaluation of
      efficacy. All patients were included in the safety analysis. RESULTS: Of the
      patients valid for efficacy, 78% of the ciprofloxacin plus metronidazole group
      and 81% of the ceftriaxone plus metronidazole group were eligible for a switch to
      oral therapy. The clinical success rates were 98.9% and 96.9%, respectively,
      which were statistically equivalent. The clinical success rates for all patients,
      including those on continuous IV therapy, were 90.6% and 87.9%. Source control
      was achieved in more than 90% of the patients. The bacteriological eradication
      rates were similar in the two groups. Bacterial complications (e.g., surgical
      site infections, abscesses) were encountered more often in the ceftriaxone plus
      metronidazole group. CONCLUSIONS: Sequential ciprofloxacin plus metronidazole IV
      to-oral therapy was statistically equivalent to ceftriaxone plus metronidazole.
      The switch to oral therapy with ciprofloxacin plus metronidazole was as effective
      and safe as continued IV therapy in patients able to tolerate enteral feeding.

PMID- 16978078
TI  - Prospective study of use of perioperative antimicrobial therapy in general
      surgery.
AB  - BACKGROUND: Perioperative antimicrobial therapy has demonstrated efficacy in
      reducing the rate of surgical site infections in clinical trials. With the
      emergence of antibiotic resistance, the risk of reaction, and the inevitable
      financial repercussions, use of prophylactic antibiotics is not a panacea, and
      their misuse may have considerable implications. The aim of this study was to
      assess the use of antibiotics in the perioperative period in both general and
      vascular surgery procedures. METHODS: A prospective study was undertaken of 131
      patients with a mean age of 43 years (range one month-88 years), of whom 68 (51%)
      were male, who underwent twenty-seven different general or vascular surgery
      procedures over a four-week period. Each patient was evaluated from the time of
      antibiotic commencement through their operative procedure until the treatment was
      discontinued. RESULTS: A total of 73 patients (54%) received ten antibiotics,
      with 71 (97%) of these uses being prophylactic. Of the 15 appendectomies
      performed for uncomplicated appendicitis, the mean number of prophylactic
      antibiotic doses was 5.3 (range 1-12). Where they were documented, written
      postoperative directives were not adhered to in 18/27 prescriptions (66%).
      CONCLUSION: This study has demonstrated a lack of adherence to guidelines in the
      perioperative administration of antimicrobial agents. In addition, it calls
      attention to the economic implications of unnecessary prophylaxis.

PMID- 16978079
TI  - Intravenous iron following cardiac surgery does not increase the infection rate.
AB  - BACKGROUND: Intravenous iron (FeIV) has been used increasingly, alone or in
      combination with recombinant erythropoietin, to promote red cell production as
      part of a blood conservation program. Given the important role that iron plays in
      the growth of bacteria, it has been hypothesized that this use of FeIV may
      promote surgical site infection. However, this hypothesis has not yet been tested
      appropriately. To assess this hypothesis, postoperative infection rates in
      patients undergoing cardiothoracic surgery were analyzed. METHODS: Data were
      collected on 863 patients undergoing cardiopulmonary bypass surgery in 2001.
      Patients were either enrolled voluntarily in a blood conservation program in
      which they received either postoperative FeIV and erythropoietin (n=302), as
      indicated, or blood transfusions and no FeIV (n=561), as indicated, to correct
      postoperative anemia. Infections were defined according to the U.S. Centers for
      Disease Control and Prevention guidelines. RESULTS: Thirty-nine infections
      developed. The overall infection rate was 4.52%, with an infection rate of 3.97%
      in the iron-treated group (n=12) and a rate of 4.81% in the untreated group
      (n=27). When the impact of gender, age, diabetes mellitus, operating time, type
      of surgery, and blood transfusions were controlled for, FeIV did not increase the
      risk of infection (odds ratio of 1.031 for each increment of 125 mg of FeIV; 95%
      confidence interval 0.908, 1.170; p=0.64). CONCLUSIONS: There was no impact of
      FeIV on the subsequent infection rate in a cardiac surgery patient cohort,
      indicating its safety for use in the postoperative setting.

PMID- 16978080
TI  - Fever after percutaneous nephrolithotomy: contributing factors.
AB  - BACKGROUND AND PURPOSE: The exact mechanism of fever and urosepsis after
      percutaneous procedures has not been established. This research studied the
      frequency of fever after percutaneous nephrolithotomy (PCNL) and the contributing
      factors. METHODS: In a cross-sectional study, from September 2003 to March 2004,
      all 217 patients with nephrolithiasis treated with PCNL at the Labbafinegad
      Specialized Urology Center were studied. Data were collected before, during, and
      after surgery. RESULTS: The frequency of fever after PCNL was 25.8% (n=56)
      although in 62.2% of the cases (n=135), no prophylactic antibiotics had been
      administered. The mean durations of hospitalization in patients with and without
      fever were 5.4+/-2.3 and 3.4+/-1.7 days, respectively (p=0.001). Significant
      correlations were observed between fever and female sex (p=0.005), positive urine
      culture (p=0.02), and nephrostomy tube insertion (p=0.041). Other variables did
      not prove to be significant. In logistic regression analysis, female sex and
      nephrostomy tube insertion were independently related to post-operative fever.
      CONCLUSION: Although a considerable proportion of our patients had not received
      prophylactic antibiotics, the rate of fever after PCNL was no higher than is
      reported in the literature. Use of only a short course of antibiotics before
      surgery for staghorn stones did not result in a higher rate of fever. Female sex
      created a higher risk for fever, probably because of the greater propensity to
      urinary tract infection. The significant relation of a nephrostomy tube to fever
      could be attributed to its role as a foreign body or to use in more complicated
      cases.

PMID- 16978081
TI  - Infection after fingertip injury in children.
AB  - We describe two cases of severe infectious complications after trauma to the
      finger phalanges in children: osteoarticular infection of the thumb and phlegmon
      of the thumb's long flexor sheath. These complications are rare after such
      injuries, which are common and for which the appropriate treatment is often an
      issue.

PMID- 16978082
TI  - Surgical Infection Society guideline: prophylactic antibiotic use in open
      fractures: an evidence-based guideline.
AB  - BACKGROUND: Prolonged courses of broad-spectrum antibiotics are often cited as
      the standard of care for prevention of infective complications of open fractures.
      The origins of these recommendations are obscure, however, and multi-drug
      resistant systemic infections attributable to antibiotic overuse are common life
      threatening problems in current intensive care unit practice. OBJECTIVE: To
      review systematically the effects of prophylactic antibiotic administration on
      the incidence of infections complicating open fractures. DATA SOURCES:
      Computerized bibliographic search of published research and citation review of
      relevant articles. STUDY SELECTION: All published clinical trials claiming to
      evaluate, or cited elsewhere as being authoritative regarding, the role of
      antibiotics in open fracture management were identified and then evaluated
      according to published guidelines for evidence-based medicine. Only small studies
      (<20 patients), practice surveys, pharmacokinetic studies, and reviews or
      duplicative publications presenting primary data already considered were excluded
      from analysis. DATA EXTRACTION: Information on demographics, study dates,
      fracture grade, antibiotic type, duration and route of administration, surgical
      interventions, infection-related outcomes, and the methodologic quality of the
      studies was extracted by the authors. The primary results were submitted to the
      Therapeutic Agents Committee of the Surgical Infection Society for review prior
      to creation of the final consensus document. DATA SYNTHESIS: Current antibiotic
      management of open fractures is based on a small number of studies that generally
      are more than 30 years old and do not reflect current management priorities in
      trauma and critical care. With a few noteworthy exceptions, these primary studies
      suffer from a variety of methodologic problems, including co-mingling of
      prospective and retrospective data sets, absence of or inappropriate statistical
      analysis, lack of blinding, or failure of randomization. CONCLUSIONS: The data
      support the conclusion that a short course of first-generation cephalosporins,
      begun as soon as possible after injury, significantly lowers the risk of
      infection when used in combination with prompt, modern orthopedic fracture wound
      management. There is insufficient evidence to support other common management
      practices, such as prolonged courses or repeated short courses of antibiotics,
      the use of antibiotic coverage extending to gram-negative bacilli or clostridial
      species, or the use of local antibiotic therapies such as beads. Large,
      randomized, blinded trials are needed to prove or disprove the value of these
      traditional approaches. Such trials should be performed in patients with high
      grade fractures who (1) are well-stratified according to the degree of local
      injury and (2) undergo standardized fracture and wound management. Trials also
      must be powered to study the effects of extended antibiotic coverage on
      nosocomial infections. Antibiotic regimens confirmed to improve local fracture
      outcomes in such studies could then be used rationally, balancing the risks of
      local fracture-related infections and of multi-drug-resistant systemic infections
      to achieve optimal global outcomes.

PMID- 16978084
TI  - Effects of antisense oligodeoxynucleotides targeting CCR3 on the airway response
      to antigen in rats.
AB  - Asthma is characterized by airway hyperresponsiveness (AHR) and inflammation,
      consisting predominantly of eosinophils within the airway lumen and walls.
      Eosinophil recruitment to the airways is mediated mainly by eotaxin and other
      chemokines that bind to the CC-chemokine receptor-3 (CCR3), which is highly
      expressed on eosinophils. This study assessed whether topical inhibition of CCR3
      mRNA expression by phosphorothioate antisense oligodeoxynucleotides (AS-ODNs)
      modifies pulmonary eosinophilia and AHR in an antigen-induced allergic asthma
      model in Brown Norway (BN) rats. Results show that specific inhibition of CCR3
      expression in the lungs by an AS-ODN (AS4) reduced total eosinophil infiltration
      and the percentage of eosinophils into the airways of ovalbumin challenged rats.
      Moreover, reduction in CCR3 mRNA levels was correlated with a decrease in CCR3
      protein in lung tissue. In addition, AS4 treatment had no effect on circulating
      eosinophils or on eosinophils in the bone marrow. Finally, AHR was significantly
      decreased in AS4-treated rats when compared with rats treated with a mismatch AS
      ODN. In conclusion, inhibition of the expression of CCR3 decreased pulmonary
      eosinophilia and reduced AHR after antigen challenge in rats. Topical inhibition
      of CCR3 expression, using an AS-ODN, could represent a novel approach for the
      treatment of asthma.

PMID- 16978085
TI  - Small fragment homologous replacement-mediated modification of genomic beta
      globin sequences in human hematopoietic stem/progenitor cells.
AB  - An ultimate goal of gene therapy is the development of a means to correct mutant
      genomic sequences in the cells that give rise to pathology. A number of
      oligonucleotide-based gene-targeting strategies have been developed to achieve
      this goal. One approach, small fragment homologous replacement (SFHR), has
      previously demonstrated disease-specific genotypic and phenotypic modification
      after introduction of small DNA fragments (SDFs) into somatic cells. To validate
      whether the gene responsible for sickle cell anemia (beta-globin) can be modified
      by SFHR, a series of studies were undertaken to introduce sickle globin sequences
      at the appropriate locus of human hematopoietic stem/progenitor cells (HSPCs).
      The characteristic A two head right arrow T transversion in codon 6 of the beta
      globin gene was indicated by restriction fragment length polymorphic (RFLP)
      analysis of polymerase chain reaction (PCR) products generated by amplification
      of DNA and RNA. At the time of harvest, it was determined that the cells
      generally contained </=1 fragment per cell. Control studies mixing genomic DNA
      from nontransfected cells with varying amounts of the targeting SDFs did not
      indicate any PCR amplification artifacts due to the presence of residual SDF
      during amplification. RNA was analyzed after DNase treatment, thus eliminating
      the potential for SDF contamination. Stable SFHRmediated conversion of normal
      (beta (A)) to sickle (beta (S)) globin was detected at frequencies up to 13% in
      cells harvested 30-45 days posttransfection. The minimum conversion efficiency
      ranged from 0.2 to 3%, assuming modification of at least one cell per experiment
      showing conversion. Conversion of sickle (beta (S)) to normal (beta (A)) globin
      was detected up to 10 days posttransfection in lymphoblastoid cells from a sickle
      cell patient. These studies suggest that SFHR may be effective for ex vivo gene
      therapy of sickle cells in a patient's HSPCs before autologous transplantation.

PMID- 16978087
TI  - Binary hammerhead ribozymes with improved catalytic activity.
AB  - A new design of binary hammerhead ribozymes displaying high catalytic activity
      and nucleolytic stability is described. These catalytic structures consist of two
      partially complementary oligoribonucleotides, capable of assembling into the
      hammerhead-like structure without tetraloop II on binding to the RNA target. A
      series of these binary ribozymes targeting the translation initiation region of
      multiple drug resistance gene mdr1 mRNA was synthesized and assessed in terms of
      catalytic activity under single and multiple reaction turnover conditions.
      Enhanced nuclease resistance of the binary ribozymes was achieved by
      incorporation of 2'-modified nucleotides at selected positions, along with
      addition of a 3'-3'-linked thymidine cap. The new binary ribozymes exhibit higher
      RNA cleavage activity than their full-length analogs because of faster
      dissociation of cleavage products. Furthermore, an excess of one of the ribozyme
      strands provides the possibility to unfold structured regions of the target RNA
      and facilitate productive complex formation.

PMID- 16978086
TI  - Human telomerase RNA degradation by 2'-5'-linked oligoadenylate antisense
      chimeras in a cell-free system, cultured tumor cells, and murine xenograft
      models.
AB  - Ribonuclease L (RNase L) is a latent single-stranded RNA-directed
      endoribonuclease that is activated on binding to short 2'-5'-linked
      oligoadenylates (2-5A), a feature that has led to its use in antisense
      therapeutic strategies. By attaching a 2-5A moiety to the 5' terminus of standard
      antisense oligonucleotides, it is possible to activate RNase L and guide it to
      specific RNAs for degradation. These 2-5A antisense chimeras have been used
      successfully to target a variety of cellular and viral RNAs. Telomerase is a
      nuclear ribonucleoprotein complex that elongates telomeric DNA and contributes to
      cellular immortalization. Telomerase is composed of a protein catalytic subunit
      and an RNA (hTR or TERC) component, both of which are critical for holoenzyme
      activity. We describe the characterization of 2-5A antisense chimeras targeting
      the hTR component of telomerase (2-5A antihTR). Newly designed 2-5A anti-hTR
      molecules were assayed for their abilities to selectively degrade hTR in a cell
      free system. Of the five chimeras tested, one (RBI011) degraded hTR by 97%, and
      two others (RBI013 and RBI009) were also found to be highly active (73-76%
      degradation). The ability of transfected RBI011, and its homolog RBI254, to
      degrade hTR in cultured tumor cells was assessed by real-time RT-PCR. In these
      studies, RBI011 and RBI254 effectively degraded hTR in a variety of hTR-positive
      tumor cell lines. The hTR degradation studies were extended to growth assays to
      determine whether hTR ablation affected tumor cell viability or proliferation.
      RBI254 treatment resulted in reduced tumor cell viability over the course of 4
      day growth assays, effects that were augmented by cotreatment with interferon
      beta. To extend these results to an in vivo system, nude mice were implanted
      subcutaneously or orthotopically with hTR-positive prostate tumors and treated
      with RBI254. RBI254-treated mice exhibited enhanced tumor cell apoptosis and
      reduced tumor volume as compared with controls. These findings demonstrated the
      effectiveness of highly active forms of 2-5A antisense against hTR, and also
      highlight the usefulness of the cell-free system in predicting chimera efficacy
      before to inception of cell-based and in vivo studies.

PMID- 16978088
TI  - Direct comparison of in vivo antisense activity of ENA oligonucleotides targeting
      PTP1B mRNA with that of 2'-O-(2-methoxy)ethyl-modified oligonucleotides.
AB  - Protein-tyrosine phosphatase 1B (PTP1B) inhibitory activity of the 2'-O-(2
      methoxy)ethyl (2'- MOE)-modified gapmer antisense oligonucleotide, ISIS113715,
      was previously reported. This antisense oligonucleotide increases insulin
      sensitivity and normalizes plasma glucose levels in diabetic ob/ob and db/db
      mice. In the present study, the isosequential 2'-O,4'-C-ethylene-bridged nucleic
      acid (ENA)-modified oligonucleotide, ENA-1, was synthesized, and its ability to
      further improve the downregulation of PTP1B in db/db mice was examined. We
      demonstrated that, compared with ISIS113715, intraperitoneal and subcutaneous
      administration of ENA-1 more effectively decreased the plasma glucose levels in
      db/db mice. Moreover, ENA-1 decreased expression of PTP1B in the liver and fat of
      db/db mice more effectively than ISIS113715. We describe for the first time the
      functional comparison of 2'-MOE- and ENA-modified antisense oligonucleotides. Our
      data indicate that the enhancement of the efficacy of antisense oligonucleotides
      by ENA modifications is superior to that of second-generation 2'-MOE
      modifications in certain aspects.

PMID- 16978089
TI  - Complete reversal of ABCG2-depending atypical multidrug resistance by RNA
      interference in human carcinoma cells.
AB  - In the chemotherapeutic treatment of patients with disseminated neoplasms,
      multidrug resistance (MDR) is a major obstacle. ABCG2 (BCRP/MXR), a member of the
      superfamily of adenosine triphosphate-binding cassette (ABC) transporters, was
      demonstrated to be associated with "atypical" forms of multidrug-resistant
      phenotypes of cancer cells. To overcome the ABCG2-depending MDR, two specific
      anti-ABCG2 small interfering RNAs (siRNAs) were designed for transient triggering
      of the gene-silencing RNA interference (RNAi) pathway in the human gastric
      carcinoma cell line EPG85-257RNOV, exhibiting an atypical MDR phenotype. Because
      both siRNAs showed biological activity, for stable inhibition of ABCG2
      corresponding short hairpin RNA (shRNA) expression vectors were constructed. By
      treatment of EPG85-257RNOV cells with these constructs, expression of the
      targeted ABCG2-encoding mRNA and transport protein was inhibited completely.
      Furthermore, anti-ABCG2 shRNA-treated cells increased cellular drug accumulation
      to the same level measured in drug-sensitive parental cells. These effects were
      accompanied by complete reversal of the drug-resistant phenotype. Thus, the data
      indicate that siRNA- and shRNA-mediated RNAi-based gene therapy may be applicable
      in preventing and reversing ABCG2-depending atypical MDR.

PMID- 16978090
TI  - Immunostimulatory PyNTTTTGT oligodeoxynucleotides: structural properties and
      refinement of the active motif.
AB  - It is well known that synthetic oligodeoxynucleotides (ODNs) containing
      unmethylated CpG dinucleotides within a given context stimulate B lymphocytes and
      plasmacytoid dendritic cells (PDCs) of the vertebrate immune system. We have
      reported that B lymphocyte and PDC stimulation in humans could also be
      efficiently achieved by using non-CpG ODNs bearing the immunostimulatory sequence
      (motif) PyNTTTTGT, wherein Py is C or T and N is any deoxyribonucleotide. We are
      now reporting a series of studies that gives further precision regarding the
      composition of this immunostimulatory motif. The analysis of hundreds of ODNs led
      us to the conclusion that the motif for optimal CpG-independent immune
      stimulation can be represented by a sequence of the following general formula:
      PyN(T/A)(T/C/G)(T/C/G)(T/G)GT, wherein Py is C or T and N is any
      deoxyribonucleotide and wherein at least two of the positions represented within
      parentheses are Ts. Requirements for optimal ODN activity are as follows: (1) at
      least one of the versions of the general motif must be located near the central
      portion of the ODN; and (2) the ODN must be 20 or more nucleotides long.
      PyN(T/A)(T/C/G)(T/C/G)(T/G)GT ODNs are active in a phosphorothioate or in a
      phosphodiester backbone. In a phosphodiester backbone a canonical motif is
      strongly required whereas in a phosphorothioate backbone specificity is, within
      certain limits, less strict. On the other hand, PyN(T/A)(T/C/G)(T/C/G)(T/G)GT
      oligonucleotides are inactive as a double chain or as a modified
      (phosphorothioate or hydroxyl-methyl modified) or unmodified RNA backbone.

PMID- 16978092
TI  - Sooner versus later: factors associated with temporal sequencing of suicide.
AB  - There are few (if any) population-based prospective studies that provide
      information on factors associated with temporal sequencing of suicide. In this
      prospective population-based study, the National Health Interview Survey (NHIS),
      1986-1994, was linked to the National Death Index (NDI), 1986-1997, to assess
      factors that predict recent (within 12 months of interview, termed sooner)
      suicide versus suicide further in the future (more than 12 months after
      interview, termed later). Of the 653 completed suicides in the NHIS cohort, 13.4
      percent completed suicide within a year of interview, and 86.6 percent did so
      after a year. Sooner decedents were more likely to be White, less educated,
      unemployed, and to use firearms than any other method compared with later
      decedents. Surprisingly, sooner decedents had higher levels of self-rated health
      at baseline. These results have substantial implications for clinicians and other
      professionals who interact with people at highest risk of suicide. Unfortunately,
      it may be unrealistic to expect that health care providers can modify the
      behavior of individuals at highest risk of suicide.

PMID- 16978093
TI  - The social context of adolescent suicide attempts: interactive effects of parent,
      peer, and school social relations.
AB  - An ecological developmental model of adolescent suicidality was used to inform a
      hierarchical logistic regression analysis of longitudinal interactions between
      parent, peer, and school relations and suicide attempts. Reanalyzing data from
      the National Longitudinal Study of Adolescent Health, it was found that parent
      relations were the most consistent protective factor, and among boys with prior
      suicide attempts, school relations augmented the effects of parent relations when
      peer relations were low. Results indicated the need to understand suicidal
      behavior as a component of interactive social processes in the design of clinical
      interventions.

PMID- 16978094
TI  - Examining the relationship between at-risk gambling and suicidality in a national
      representative sample of young adults.
AB  - Although many clinical studies document a relationship between gambling and
      suicidality, evidence of this association in general population surveys has been
      mixed. Probing this association in a nationally representative sample of young
      adults with data from the National Longitudinal Survey of Adolescent Health, we
      made same gender comparisons of depression and suicidality between 298 at-risk
      gamblers and 13,000 others. Although gamblers of both genders showed higher
      depression, only females reported significantly higher suicide thoughts and
      attempts. Males with gambling problems were no more likely than nongamblers to
      have suicide thoughts or to make prior suicide attempts on three separate
      measurement occasions.

PMID- 16978095
TI  - Does availability of mental health resources prevent recurrent suicidal behavior?
      An ecological analysis.
AB  - This study examines whether availability of mental health resources in the county
      of residence is associated with subsequent suicidal behavior after a previous
      suicide attempt. Among 10,922 individuals who attempted suicide in Colorado
      between 1998 and 2002, residence in a county that offered a minimum safety-net of
      mental health services significantly reduced the risk of suicidal behavior for at
      least 1 year after the index attempt. Safety-net services included mental health
      treatment, crisis treatment, and case management. These results suggest one
      strategy for prevention of suicidal behavior that could inform state-level health
      policy development and resource allocation.

PMID- 16978096
TI  - Grief shortly after suicide and natural death: a comparative study among spouses
      and first-degree relatives.
AB  - Chronic dysfunction after complicated grief is not rare and emphasizes the need
      to identify bereaved individuals at risk. Three months following bereavement,
      self-reported psychiatric and general health of 153 relatives of 74 suicides was
      worse than of 70 relatives of 39 natural deaths. Moreover, the felt need for
      professional help was higher among the former, even after adjustment for
      expectedness of death, sociodemographic differences, and relatives'/spouses'
      neuroticism. This suggests that suicide-bereaved individuals may constitute a
      high-risk group of mourners in need of targeted postvention.

PMID- 16978097
TI  - Suicide in peacekeepers: risk factors for suicide versus accidental death.
AB  - To investigate risk factors for suicide in veterans of peacekeeping, 43 suicides
      and 41 fatal accidents in Norwegian peacekeepers (1978 to 1995) were compared in
      a psychological autopsy study. Mental health problems were the most important
      risk factor for suicide. Both living alone and the break-up of a love
      relationship contributed uniquely to suicide risk, even when controlling for
      mental health problems. No peacekeeping-related factor was associated with
      suicide. Preventive measures should focus on firearms control, improved detection
      systems for mental health problems in the military, and peer support through
      veterans' associations.

PMID- 16978098
TI  - Cognitive vulnerability to depression, rumination, hopelessness, and suicidal
      ideation: multiple pathways to self-injurious thinking.
AB  - In order to advance the detection and prevention of suicide, recent research has
      focused on predictors of suicidal ideation and behavior such as negative
      cognitive styles, dysfunctional attitudes, hopelessness, and rumination. In this
      study the relationships among these risk factors in the context of the Attention
      Mediated Hopelessness (AMH) theory of depression are examined. One hundred and
      twenty-seven undergraduates in the Cognitive Vulnerability to Depression (CVD)
      project were followed for 2.5 years. The CVD project followed initially
      nondepressed freshmen, at either high or low cognitive risk for depression, in
      order to predict onsets and recurrences of depressive disorders. The presence and
      duration of suicidal ideation were predicted prospectively by rumination and
      hopelessness, and hopelessness partially mediated the relationship between
      rumination and ideation and fully mediated the association between rumination and
      duration of suicidality. Further, rumination mediated the relationship between
      cognitive vulnerability and suicidal ideation.

PMID- 16978099
TI  - Soluble interleukin 2 receptor levels, temperament and character in formerly
      depressed suicide attempters compared with normal controls.
AB  - An imbalance of the immune system and mixed personality profiles in suicide
      attempters have been reported. As suicidal behavior is common in patients with
      psychiatric disorders within the spectrum of depressive features, in this study
      we measured soluble interleukin-2 receptor concentrations in plasma (sIL-2R) and
      investigated temperament and character profile and their potential correlation in
      formerly depressed patients with a history of suicide attempt. We studied sIL-2R
      levels in plasma and personality characteristics (using Cloninger's Temperament
      and Character Inventory [TCI]) of formerly depressed patients who had attempted
      suicide a mean of 3 years previously (n = 25), and age and gender matched normal
      controls (n = 25). There was no significant difference in sIL-2R levels between
      formerly depressed suicide attempters and age and gender matched normal controls
      (0.23 ng/ml +/- 0.25 vs. 0.19 ng/ml +/- 0.16). When compared to normal controls,
      suicide attempt patients had a significantly higher score on the temperament
      dimension "harm avoidance" and a lower score on the character dimension "self
      directedness." No significant correlation was found between sIL-2R values and TCI
      dimensions. We propose that the liability to suicidal behavior among suicide
      attempters susceptible to depressive symptomatology may be related to high harm
      avoidance and low self-directedness.

PMID- 16978100
TI  - Social work education in suicide intervention and prevention: an unmet need?
AB  - Research shows that social work graduate programs offer little education in
      suicide prevention and intervention, yet social workers' experiences and
      attitudes regarding suicide education are unknown. This Web-based survey of 598
      social workers found that almost all respondents had worked with at least one
      suicidal client, but most received little, if any, training in suicide prevention
      or intervention while in graduate school. Respondents largely viewed their social
      work program's training in suicide prevention and intervention as inadequate.
      Implications for social work education and practice are discussed.

PMID- 16978101
TI  - Suicide risk among persons with foreign background in Denmark.
AB  - There is a dearth of knowledge about factors correlated with suicide risk among
      minority groups in Western societies. In the present study we compared suicide
      risk among persons with foreign background with that of the majority population
      to determine whether certain minority groups are at a particular risk for
      suicide, as well as to illuminate gender differences herein. Suicide risk was
      generally higher among persons with foreign background compared with the majority
      population and the risk was highest among Nordic-born persons. Overall, suicide
      risk was significantly lower among Asian-born persons; however, there were gender
      differences in correlations between ethnicity and suicide risk.

PMID- 16978104
TI  - Improving human health protection.

PMID- 16978105
TI  - Questions value of vacuolar hepatopathy study.

PMID- 16978106
TI  - Assessing veterinary medical education with regard to the attraction, admission,
      and education of students interested in food supply veterinary medicine and
      retention of student interest in a career in the food supply sector.

PMID- 16978107
TI  - What is your diagnosis? Multiple myeloma.

PMID- 16978108
TI  - What is your diagnosis? Cryptococcosis.

PMID- 16978109
TI  - What is your neurologic diagnosis? Infiltrative lipoma of the thoracic spinal
      cord.

PMID- 16978110
TI  - Theriogenology question of the month. Unilateral abdominal cryptorchidism.

PMID- 16978111
TI  - Animal behavior case of the month. Separation anxiety.

PMID- 16978112
TI  - Report of the 2006 National Animal Disaster Summit.

PMID- 16978113
TI  - Clinical evaluation of dietary modification for treatment of spontaneous chronic
      kidney disease in cats.
AB  - Objective-To determine whether a renal diet modified in protein, phosphorus,
      sodium, and lipid content was superior to an adult maintenance diet in minimizing
      uremic episodes and mortality rate in cats with stage 2 or 3 chronic kidney
      disease (CKD). Design-Double-masked, randomized, controlled clinical trial.
      Animals-45 client-owned cats with spontaneous stage 2 or 3 CKD. Procedures-Cats
      were randomly assigned to an adult maintenance diet (n = 23 cats) or a renal diet
      (22) and evaluated trimonthly for up to 24 months. Efficacy of the renal diet,
      compared with the maintenance diet, in minimizing uremia, renal-related deaths,
      and all causes of death was evaluated. Results-Serum urea nitrogen concentrations
      were significantly lower and blood bicarbonate concentrations were significantly
      higher in the renal diet group at baseline and during the 12- and 24-month
      intervals. Significant differences were not detected in body weight; Hct; urine
      protein-to-creatinine ratio; and serum creatinine, potassium, calcium, and
      parathyroid hormone concentrations. A significantly greater percentage of cats
      fed the maintenance diet had uremic episodes (26%), compared with cats fed the
      renal diet (0%). A significant reduction in renal-related deaths but not all
      causes of death was detected in cats fed the renal diet. Conclusions and Clinical
      Relevance-The renal diet evaluated in this study was superior to an adult
      maintenance diet in minimizing uremic episodes and renalrelated deaths in cats
      with spontaneous stage 2 or 3 CKD.

PMID- 16978114
TI  - Evaluation of the association between microalbuminuria and the urine albumin
      creatinine ratio and systemic disease in dogs.
AB  - OBJECTIVE: To evaluate semiquantitative and quantitative assays for
      microalbuminuria and determination of the urine albumin-creatinine (UAC) ratio in
      detection of systemic disease in dogs without overt proteinuria. DESIGN:
      Prospective study. ANIMALS: 408 dogs. PROCEDURES: Urine samples that had been
      obtained from dogs for which a complete medical record was available and in which
      results of a dipstick test for urine protein were negative were evaluated. Urine
      protein-creatinine ratios (cutoff values, 0.5 and 0.1), semiquantitative and
      quantitative microalbuminuria values (cutoff value, 1 mg/dL), and UAC ratios
      (cutoff values, 100 and 200 mg/g) were determined. Clinical diagnoses rendered
      within 3 months of enrollment in the study were recorded. Sensitivity and
      specificity were determined with disease status serving as the standard.
      Associations with clinical diagnosis, sex, age, BUN and serum creatinine
      concentrations, blood pressure, results of bacterial culture of urine,
      temperature, pyuria, hematuria, and bacteriuria were evaluated by use of logistic
      regression analysis. RESULTS: 48 dogs were healthy, and 360 had at least 1
      disease. Significant associations were detected between age, presence of disease,
      presence of neoplastic disease, BUN and serum creatinine concentrations, and
      hematuria and results of 1 or both of the microalbuminuria assays. CONCLUSIONS
      AND CLINICAL RELEVANCE: Microalbuminuria was associated with underlying disease.
      The sensitivity and specificity of the semiquantitative microalbuminuria test for
      detection of systemic disease were superior to those of other tests.
      Microalbuminuria testing in conjunction with other screening procedures may
      increase diagnosis of subclinical disease, but a prospective study in which the
      predictive values of screening tests are evaluated, with and without
      microalbuminuria determination, is needed.

PMID- 16978115
TI  - Aromatherapy for travel-induced excitement in dogs.
AB  - OBJECTIVE: To evaluate the efficacy of the ambient odor of lavender as a
      treatment for travel-induced excitement in dogs. DESIGN: Clinical trial. Animals
      32 dogs with a history of travel-induced excitement in owners' cars. PROCEDURES:
      Each dog was studied during travel in the owner's car to a familiar walking site
      during 2 conditions of olfactory stimulation. The first condition was a control
      condition, during which dogs were exposed to no odor other than that arising
      naturally from the environment. The second condition was an experimental
      condition during which dogs were exposed to the ambient odor of lavender. Dogs'
      behavior was recorded during the car journey for 3 consecutive days under the
      control condition and for 3 consecutive days under the experimental condition.
      The percentage of time spent moving, standing, sitting, resting, and vocalizing
      in each condition of olfactory stimulation was quantified for each dog. RESULTS:
      Dogs spent significantly more time resting and sitting and less time moving and
      vocalizing during the experimental condition. There was no significant
      relationship between dogs' behavior and sex, castration status, day, or the order
      of exposure to each olfactory condition. CONCLUSIONS AND CLINICAL RELEVANCE:
      Traditional treatments for travel-induced excitement in dogs may be time
      consuming, expensive, or associated with adverse effects. Aromatherapy in the
      form of diffused lavender odor may offer a practical alternative treatment for
      travel-induced excitement in this species.

PMID- 16978116
TI  - Drug distribution and stability in extemporaneous preparations of meloxicam and
      carprofen after dilution and suspension at two storage temperatures.
AB  - OBJECTIVE: To determine dispersion uniformity and stability of meloxicam and
      carprofen in extemporaneous preparations stored for 28 days. DESIGN: Prospective
      study. SAMPLE POPULATION: Meloxicam and carprofen (commercial formulations) were
      compounded (day 0) with deionized water (DW), 1% methylcellulose gel (MCG), MCG
      and simple syrup (SS; 1:1 mixture), or a suspending and flavoring vehicle
      combination (SFVC; 1:1 mixture) to nominal drug concentrations of 0.25, 0.5, or
      1.0 mg/mL and 1.25, 2.5, or 5.0 mg/mL, respectively. PROCEDURES: Preparations
      were stored at approximately 4 degrees C (39.2 degrees F) or 22 degrees C (71.6
      degrees F). For each preparation, drug concentrations were determined and drug
      stability was evaluated at intervals during storage; on days 0 and 28, pH values
      were measured and bacterial cultures were initiated. RESULTS: In meloxicam-DW,
      meloxicam-MCG (0.25 mg/mL), and meloxicam-MCG (0.5 mg/mL) preparations, drug
      distribution was uniform (coefficient of variation < 10%); > 90% of the original
      drug concentration was maintained for 28 days. Despite uniform drug distribution
      of the carprofen-SFVC preparations, most retained > or = 90% of the original drug
      concentration for only 21 days. Use of the MCG-SS combination resulted in foamy
      preparations of unacceptable variability. After 28 days, pH decreased slightly in
      meloxicam-DW and meloxicam-MCG preparations (0.17 +/- 0.04 and 0.21 +/- 0.04,
      respectively). Carprofen-SFVC (2.5 mg/mL) and carprofen-MCG-SS (5.0 mg/mL)
      preparations stored at 22 degrees C for 28 days yielded bacterial growth.
      CONCLUSIONS AND CLINICAL RELEVANCE: DW, MCG, and the SFVC can be used
      successfully for extemporaneous preparation of meloxicam and carprofen for
      administration to small exotic animals. Refrigeration is recommended for
      preparations of meloxicam-DW and carprofen-SFVC.

PMID- 16978117
TI  - Diagnosis and surgical management of vascular ectasia in a dog.
AB  - CASE DESCRIPTION: An 8-year-old male Golden Retriever was evaluated because of an
      8-week history of intermittent diarrhea with melena and hematochezia that were
      not responsive to medical treatment and resulted in severe anemia. CLINICAL
      FINDINGS: Exploratory celiotomy with intestinal and colonic biopsy revealed mild
      enterocolitis but did not result in diagnosis of the cause of melena and
      hematochezia. Endoscopy of the upper portion of the gastrointestinal tract and
      colonoscopy were performed. Multifocal areas of coalescing, tortuous mucosal
      blood vessels were observed in the cecum and all regions of the colon. A
      diagnosis of vascular ectasia (VE) was made on the basis of the endoscopic and
      histologic appearance of the lesions. TREATMENT AND OUTCOME: An ileorectal
      anastamosis was performed. Melena and hematochezia resolved within 3 days after
      surgery, and the anemia resolved within 6 weeks after surgery. Surgical resection
      of the cecum and colon and feeding of a highly digestible diet resulted in long
      term (22 months) resolution of clinical signs. CLINICAL RELEVANCE: Initial
      exploratory celiotomy with intestinal and colonic biopsy failed to reveal the VE
      lesions responsible for the melena, hematochezia, and anemia. Endoscopic
      evaluation was necessary for detection of the colonic VE lesions. Surgical
      resection of the cecum and colon and feeding of a highly digestible diet may
      result in a favorable outcome in affected dogs.

PMID- 16978119
TI  - Portal site metastasis of invasive mesothelioma after diagnostic thoracoscopy in
      a dog.
AB  - CASE DESCRIPTION: A 10-year-old Golden Retriever evaluated because of recurrent
      pericardial and pleural effusion underwent thoracoscopy with biopsy of the pleura
      and mediastinum. CLINICAL FINDINGS: Before thoracoscopy, 5 L of serosanguinous
      fluid was removed from the pleural cavity via thoracocentesis. During
      thoracoscopic exploration, it was observed that the parietal pleura and
      mediastinum were covered by miliary white to tan nodules 1 to 3 mm in diameter.
      Biopsy specimens were obtained, and partial pericardiectomy was performed. Portal
      sites were closed routinely. Cytologic evaluation of the pleural fluid revealed
      high protein concentration and cellularity, with cellular changes consistent with
      an exfoliating carcinoma. Results of bacterial culture were negative. TREATMENT
      AND OUTCOME: Carboplatin was administered via intracavitary instillation, and
      prednisone was administered orally. Twenty-one days later, 1 firm, irregularly
      shaped 6.5 x 3-cm mass and 4 smaller masses were detected in the area of the left
      thoracic wall where the cannula had been inserted during thoracoscopy. Histologic
      analysis of tissue from the masses collected at necropsy confirmed that they were
      malignant tumors with similar appearance to the pleural mesothelioma and
      immunohistochemical staining properties identical to those of the primary tumor.
      CLINICAL RELEVANCE: Although thoracoscopy is associated with less postoperative
      pain, shorter hospitalization times, and faster patient recovery than sternotomy
      procedures, complications are also possible with minimally invasive endoscopic
      surgery. Portal site metastasis can develop from contamination of portal sites
      with cells on instruments or cannulas or via leakage of effusion fluid. Although
      rare, this potential complication should be discussed with owners prior to
      performing the procedure.

PMID- 16978120
TI  - Toggle rod stabilization for treatment of hip joint luxation in dogs: 62 cases
      (2000-2005).
AB  - OBJECTIVE: To determine outcome of open toggle rod stabilization in dogs with
      luxation of the hip joint. Design-Retrospective case series. ANIMALS: 62 dogs.
      PROCEDURES: Information on signalment, surgical procedure, and postoperative care
      was obtained from the medical records. A questionnaire was sent to all owners to
      solicit follow-up information. RESULTS: The distribution for time between
      luxation and surgery was bimodal, with 24 (39%) dogs examined < or = 2 days after
      injury and 23 (37%) examined > 7 days after injury. Postoperative complications
      developed in 16 of the 62 (26%) dogs, with complications developing within 1 week
      after surgery in 10 of the 16. The most common complication was reluxation, which
      occurred in 7 dogs. Dogs in which surgery time was < 2 hours were significantly
      less likely to have a reluxation (2/40 [5%]) than were dogs in which surgery time
      was > or = 2 hours (5/22 [23%]). When asked to rate current limb function (0 = no
      lameness and 5 = non-weightbearing lame) a minimum of 6 months after surgery, 23
      of 27 (85%) owners indicated a score of 0 or 1. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results of the present study suggest that toggle rod stabilization is
      an effective treatment for hip joint luxation in dogs. However, complications,
      particularly reluxation, were common.

PMID- 16978121
TI  - Control of selection bias in parallel-group controlled clinical trials in dogs
      and cats: 97 trials (2000-2005).
AB  - OBJECTIVE: To determine how selection bias (allocation bias) was controlled in
      published clinical trials. DESIGN: Retrospective study. SAMPLE POPULATION: 97
      parallel-group controlled clinical trials published from January 2000 through
      December 2005 in 12 peer-reviewed journals. PROCEDURES: Journals were hand
      searched to identify eligible reports. Details concerning allocation of animals
      to study groups, baseline characteristics of the groups, and the number of
      animals allocated to each group were recorded. RESULTS: Randomization was the
      stated method of allocating animals to groups in 87% of the reports, yet in only
      11% of reports were both randomization of the group allocation process and
      concealment of the allocation sequence described. Studies reported as randomized
      were more likely to report baseline characteristics of the study groups for
      comparison than studies that did not report randomization (88% vs 54%). Studies
      in which baseline group characteristics were reported had more subjects allocated
      to each study group (median, 16) than those that did not (median, 11).
      CONCLUSIONS AND CLINICAL RELEVANCE: Randomization was reported as the method of
      allocating study animals to groups in most publications, indicating that the
      potential power of randomization in controlling selection bias is appreciated by
      clinical investigators seeking to determine the efficacy of an intervention.
      However, in most reports, little corroborating information was included to
      support the claim. The absence of this information makes it difficult for
      practitioners to critically review the impact of bias on study results and make
      informed decisions regarding patients.

PMID- 16978128
TI  - The pilgrim at high altitude.

PMID- 16978132
TI  - High altitude adaptation in Tibetans.
AB  - Since the beginning of the Himalayan climbing era, the anecdotal extraordinary
      physical performance at high altitude of Sherpas and Tibetans has intrigued
      scientists interested in altitude adaptation. These ethnic groups may have been
      living at high altitude for longer than any other population, and the hypothesis
      of a possible evolutionary genetic adaptation to altitude makes sense. Reviewed
      here is the evidence as to whether Tibetans are indeed better adapted for life
      and work at high altitude as compared to other populations and, if so, whether
      this better adaptation might be inborn. Tibetans, compared to lowlanders,
      maintain higher arterial oxygen saturation at rest and during exercise and show
      less loss of aerobic performance with increasing altitude. Tibetans have greater
      hypoxic and hypercapnic ventilatory responsiveness, larger lungs, better lung
      function, and greater lung diffusing capacity than lowlanders. Blood hemoglobin
      concentration is lower in Tibetans than in lowlanders or Andeans living at
      similar altitudes. Tibetans develop only minimal hypoxic pulmonary hypertension
      and have higher levels of exhaled nitric oxide than lowlanders or Andeans.
      Tibetans' sleep quality at altitude is better and they desaturate less at night.
      Several of these findings are also found in Tibetans born at low altitude when
      exposed for the first time to high altitude once adult. In conclusion, Tibetans
      indeed seem better adapted to life and work at high altitude, and this superior
      adaptation may very well be inborn, even though its exact genetic basis remains
      to be elucidated.

PMID- 16978133
TI  - Genetic contribution of the endothelial nitric oxide synthase gene to high
      altitude adaptation in sherpas.
AB  - The Sherpas' adaptation to high altitude has been hypothesized as being due to a
      genetic basis since the beginning of the last century, but this has yet to be
      demonstrated. We randomly enrolled 105 Sherpas in Namche Bazaar (3440 m) and 111
      non-Sherpa Nepalis in Kathmandu (1330 m) in Nepal. The genotypes of Glu298Asp and
      eNOS4b/a polymorphisms of the endothelial nitric oxide synthase (eNOS) gene were
      identified. The metabolites of nitric oxide (NO( x ): nitrite and nitrate) in
      serum were measured. The frequencies of the Glu and eNOS4b alleles were
      significantly higher in Sherpas (Glu: 87.5%; eNOS4b: 96.7%) than in non-Sherpas
      (Glu: 77.9%, p = 0.036; eNOS4b: 90.5%, p = 0.009). In addition, the combination
      of the wild types of Glu298Glu and eNOS4b/b was significantly greater in Sherpas
      (66.7%) than non-Sherpas (47.7%, p = 0.008). However, the serum NO( x ) was
      significantly lower in Sherpas (53.2 +/- 4.6 micromol/L) than in non-Sherpas
      (107.3 +/- 9.0 micromol/L, p < 0.0001). The wild alleles of the Glu298Asp and
      eNOS4b/a polymorphisms of the eNOS gene may be a benefit for the Sherpas'
      adaptation to high altitude. The nitric oxide metabolites (NO( x )) in serum vary
      individually, thus it is not a reliable indicator for endogenous nitric oxide
      production.

PMID- 16978134
TI  - Endothelial nitric oxide synthase polymorphisms do not influence pulmonary artery
      systolic pressure at altitude.
AB  - Previous genetic association studies in high-risk subjects have suggested that
      polymorphisms in the gene encoding endothelial nitric oxide synthase (eNOS) may
      be associated with susceptibility to high altitude pulmonary edema (HAPE). We
      aimed to determine whether eNOS polymorphisms influence systolic pulmonary artery
      pressure measurements (PASP) in healthy trekkers ascending to high altitude. We
      examined two polymorphisms of the eNOS gene in Caucasian volunteers: Glu298Asp
      variant and 27-base pair (bp) variable number of tandem repeats polymorphism (27
      bp VNTR). In 33 subjects, the relationships between polymorphisms and absolute
      pulmonary artery systolic pressure measurements (PASP), determined by
      echocardiography, were assessed at sea level and 1, 3, and 7 days after acute
      ascent by vehicle transport to 5200 m. As expected, there was a significant rise
      in pulmonary artery pressure on ascent to high altitude. By contrast, at sea
      level and at each time point at high altitude, no difference was found in mean
      PASP according to eNOS polymorphism. We found no association of Glu298Asp and 27
      bp VNTR polymorphisms in the eNOS gene with PASP in a population of healthy
      trekkers at low or high altitude.

PMID- 16978135
TI  - The role of dehydroepiandrosterone levels on physiologic acclimatization to
      chronic mountaineering activity.
AB  - Previous studies have reported that glucose tolerance can be improved by short
      term altitude living and activity. However, not all literature agrees that
      insulin sensitivity is increased at altitude. The present study investigated the
      effect of a 25-day mountaineering activity on glucose tolerance and its relation
      to serum levels of dehydroepiandrosterone-sulfate (DHEA-S) and tumor necrosis
      factor-alpha (TNF-alpha) in 12 male subjects. On day 3 at altitude, we found that
      serum DHEAS was reduced in the subjects with initially greater DHEA-S value,
      whereas the subjects with initially lower DHEA-S remained unchanged. To further
      elucidate the role of DHEA-S in acclimatization to mountaineering activity, all
      subjects were then divided into lower and upper halves according to their sea
      level DHEA-S concentrations: low DHEA-S (n = 6) and high DHEA-S groups (n = 6).
      Glucose tolerance, insulin level, and the normal physiologic responses to
      altitude exposure, including hematocrit, hemoglobin, erythropoietin (EPO), and
      cortisol were measured. We found that glucose and insulin concentrations on an
      oral glucose tolerance test were significantly lowered by the mountaineering
      activity only in the high DHEA-S group. Similarly, hematocrit and hemoglobin
      concentration in altitude were increased only in the high DHEA-S group. In
      contrast, the low DHEA-S subjects exhibited an EPO value at sea level and
      altitude greater than the high DHEA-S group, suggesting an EPO resistance. The
      findings of the study imply that DHEA-S is essential for physiologic
      acclimatization to mountaineering challenge.

PMID- 16978136
TI  - Chronic hypoxia diminishes the proliferative response of Guinea pig uterine
      artery vascular smooth muscle cells in vitro.
AB  - The pregnancy-related size enlargement of the guinea pig uterine artery is
      partially accomplished by hyperplasia in all layers of the vessel wall. We sought
      to determine the separate and combined effects of chronic hypoxia and pregnancy
      on the proliferative capacity of uterine artery vascular smooth muscle cells (UA
      VSMCs). We established primary UA VSMC cultures from a total of 13 guinea pigs
      using an enzymatic digestion technique. Animals were bred and kept in normoxia or
      hypoxia (P(B) = 463 mmHg, simulated elevation = 3962 m) for 45 days, a duration
      equivalent to midpregnancy in the guinea pig 63-day gestation. Nonpregnant
      matched controls were included. The proliferative response of UA VSMCs to 1, 3, 5
      or 7 days of serum stimulation in vitro was compared. Exposure to hypoxia reduced
      UA VSMC proliferative response to serum stimulation relative to that seen in
      cells harvested from normoxic females. The inhibitory effect was present both in
      cells harvested from nonpregnant and pregnant animals and resulted in a lower UA
      VSMC proliferative response in the cells harvested from hypoxic compared with
      normoxic pregnant animals. Our data were consistent with our hypothesis that
      chronic maternal hypoxia compromises the capacity for growth and remodeling of
      the uterine artery during pregnancy, perhaps by interfering with the ability of
      vascular smooth muscle cells to de-differentiate to a proliferative phenotype.
      Noteworthy was that such effects of chronic hypoxia were retained in cultured
      cells.

PMID- 16978137
TI  - Lipid profile, waist circumference, and body mass index in a high altitude
      population.
AB  - Some studies have found different distribution patterns for the lipid profile of
      high altitude populations, having found the majority of them a more favorable one
      in these subjects. The objective of this study is to describe the lipid profile
      of a high altitude population and relate it to the waist circumference, body mass
      index, gender, and age. A descriptive study was done in an adult population, 30
      yr old and above, of the town of San Pedro de Cajas (SPC), Peru, located at 4100
      m (13,450 ft) above sea level. One hundred and two representative individuals (38
      males and 64 females) were included. HDL cholesterol and triglyceride means were
      elevated, whereas total cholesterol means were average, and LDL cholesterol means
      were low. The BMI mean was 25.4 +/- 3.7. We observed a high prevalence of
      hypercholesterolemia (34.3%) and hypertriglyceridemia (53.9%) in both genders.
      Higher prevalences of low HDL (45.3%), abnormal waist circumference (64%), and
      obesity (14.1%) were found in women (p < 0.001). A higher prevalence of low HDL
      in overweight/obese (74.2%) and abnormal waist circumference (77.4%) subjects was
      evident (p < 0.001). We found high prevalences of hypercholesterolemia and
      hypertriglyceridemia for both genders and important prevalences of risk factors
      for cardiovascular disease and coronary heart disease, such as
      hypertriglyceridemia, low HDL, abnormal waist circumference, and obesity, in high
      altitude natives, especially in women.

PMID- 16978138
TI  - Successful treatment of severe acute mountain sickness and excessive pulmonary
      hypertension with dexamethasone in a prepubertal girl.

PMID- 16978142
TI  - Interactions between mosquito larvae and species that share the same trophic
      level.
AB  - Ecological theory predicts, and empirical research shows, that species sharing
      the same trophic level as a target species (hereafter controphic species) can
      have large direct and indirect effects on the target species by sharing resources
      and/or by serving as alternative prey to predators. Yet, the roles of controphic
      species of mosquito larvae in affecting mosquito populations have received little
      attention. Published empirical evidence, although scarce, suggests that
      controphic species such as zooplankton and anuran larvae compete with mosquito
      larvae, can positively affect mosquito larvae by consuming bacteria that are
      pathogenic to mosquito larvae, reduce predation on mosquito larvae by serving as
      alternative prey, and ultimately cause increased predation on mosquito larvae by
      causing a numerical response in the predator. We conclude that more extensive
      theoretical and empirical studies in elucidating the roles of controphic species
      will better allow us to predict mosquito population dynamics and allow for better
      management of mosquitoes.

PMID- 16978143
TI  - Cellular search migrations in normal development and carcinogenesis.
AB  - This review describes the large group of morphogenetic processes designated as
      search migrations. Search migrations typically include two stages: i) search,
      when a group of cells or of the cytoplasmic processes migrate over the cell-free
      spaces, and ii) choice, the stage when migrating cells reach specific loci where
      they stop and undergo specific differentiations induced by local factors such as
      cell-cell contacts and humoral agents. Migrating cells that do not meet their
      targets usually undergo apoptosis. Numerous examples of search migrations range
      from gastrulation to formation of axon-muscle connections. Critical stages of
      carcinogenesis such as acquisition of cell ability for invasion may be regarded
      as the genetic aberration of normal search migration: cancer cells perform an
      endless search but cannot make final choice.

PMID- 16978144
TI  - Revision of the antigen receptor of T-lymphocytes.
AB  - This review considers a crucially new mechanism of T-cell antigen-recognizing
      repertoire formation. It includes the revision of T-cell antigen receptor (TCR),
      which implies the secondary rearrangement of TCR genes in peripheral T
      lymphocytes and surface expression of a new antigen receptor with altered
      specificity. Factors and mechanisms involved in the induction of this process
      have been analyzed. Certain attention is paid to a possible role of TCR revision
      in the formation of peripheral tolerance in the processes of "avidity maturation"
      of T-lymphocytes during immune response and also negative consequences related to
      appearance of potentially autoreactive clones in the periphery.

PMID- 16978145
TI  - Participation of proteolytic enzymes in the interaction of plants with
      phytopathogenic microorganisms.
AB  - Different forms of participation of proteolytic enzymes in pathogenesis and plant
      defense are reviewed. Together with extracellular proteinases, phytopathogenic
      microorganisms produce specific effectors with proteolytic activity and are able
      to act on proteins inside the plant cell. In turn, plants use both extracellular
      and intracellular proteinases for defense against phytopathogenic microorganisms.
      Among the latter, a special role belongs to vacuolar processing enzymes
      (legumains), which perform the function of caspases in the plant cell.

PMID- 16978146
TI  - New viral vector for efficient production of target proteins in plants.
AB  - A new potato virus X (PVX)-based viral vector for superproduction of target
      proteins in plants has been constructed. The triple gene block and coat protein
      gene of PVX were substituted by green fluorescent protein. This reduced viral
      vector was delivered into plant cells by agroinjection (injection of
      Agrobacterium tumefaciens cells, carrying viral vector cDNA within T-DNA, into
      plant leaves), and this approach allowed to dramatically reduce the size of the
      vector genome. The novel vector can be used for production of different proteins
      including pharmaceuticals in plants.

PMID- 16978147
TI  - Ubiquitin-protein ligase parkin and its role in the development of Parkinson's
      disease.
AB  - Parkin is a protein encoded by the corresponding parkin gene. It exhibits
      ubiquitin-protein ligase activity. In this review, we analyze domain structure,
      substrate specificity, subcellular localization of parkin, and regulation of its
      activity. Then we discuss data on the effects of various mutations in the parkin
      gene on structure and functions of this protein and results obtained with parkin
      knock-out animals. Better understanding of parkin biochemistry, its
      compartmentalization, functions, and altered functions would help the development
      of new approaches for the treatment of both inherited and sporadic cases of
      Parkinson's disease.

PMID- 16978148
TI  - Chemiluminescent in vitro estimation of the inhibitory constants of antioxidants
      ascorbic and uric acids in Fenton's reaction in urine.
AB  - The goal of this research was to measure in vitro the inhibitory constants of the
      antioxidants ascorbic and uric acid in urine, with lucigenin enhanced
      chemiluminescence (CL) in Fenton's system. Maximum CL emission is registered in
      urine containing H2O2 (5.10(-4) M), Fe2+ (5.10(-5) M), EDTA (5.10(-5) M), and
      chemical enhancer lucigenin (10(-4) M) at pH 5.5 and 36 degrees C. Ascorbic acid
      exhibits up to 4-fold stronger antioxidant effect than uric acid. The constants
      of antioxidant inhibition in urine were measured at concentrations 10(-3) and 10(
      4) M: for ascorbic acid, 5.92 +/- 0.04 and 24.05 +/- 1.82 micromol.sec(-1); for
      uric acid, 1.60 +/- 0.02 and 21.45 +/- 0.97 micromol.sec(-1), respectively. Three
      phases of CL kinetics of urine are well observed: spontaneous CL (0-10 sec), fast
      flash of CL (10-50 sec), and latent period (50-300 sec). The antioxidant
      efficiency of ascorbic and uric acids in the final stage of catabolic processes
      in the body is discussed.

PMID- 16978149
TI  - Arachidonic acid enhances intracellular [Ca2+]i increase and mitochondrial
      depolarization induced by glutamate in cerebellar granule cells.
AB  - Maturation of primary neuronal cultures is accompanied by an increase in the
      proportion of cells that exhibit biphasic increase in free cytoplasmic Ca2+
      ([Ca2+]i) followed by synchronic decrease in electrical potential difference
      across the inner mitochondrial membrane (DeltaPsim) in response to stimulation of
      glutamate receptors. In the present study we have examined whether the appearance
      of the second phase of [Ca2+]i change can be attributed to arachidonic acid (AA)
      release in response to the effect of glutamate (Glu) on neurons. Using primary
      culture of rat cerebellar granule cells we have investigated the effect of AA (1
      20 microM) on [Ca2+]i, DeltaPsim, and [ATP] and changes in these parameters
      induced by neurotoxic concentrations of Glu (100 microM, 10-40 min). At =10
      microM, AA caused insignificant decrease in DeltaPsim without any influence on
      [Ca2+]i. The mitochondrial ATPase inhibitor oligomycin enhanced AA-induced
      decrease in DeltaPsim; this suggests that AA may inhibit mitochondrial
      respiration. Addition of AA during the treatment with Glu resulted in more
      pronounced augmentation of [Ca2+]i and the decrease in DeltaPsim than the changes
      in these parameters observed during independent action of AA; removal of Glu did
      not abolish these changes. An inhibitor of the cyclooxygenase and lipoxygenase
      pathways of AA metabolism, 5,8,11,14-eicosatetraynoic acid, increased the
      proportion of neurons characterized by Glu-induced biphasic increase in [Ca2+]i
      and the decrease in DeltaPsim. Palmitic acid (30 microM) did not increase the
      percentage of neurons exhibiting biphasic response to Glu. Co-administration of
      AA and Glu caused 2-3 times more pronounced decrease in ATP concentrations than
      that observed during the independent effect of AA and Glu. The data suggest that
      AA may influence the functional state of mitochondria, and these changes may
      promote biphasic [Ca2+]i and DeltaPsim responses of neurons to the neurotoxic
      effect of Glu.

PMID- 16978150
TI  - Plasmid DNA acquires immunogenicity on exposure to singlet oxygen.
AB  - In the present study, the effect of singlet oxygen (1O2) (generated by
      ultraviolet (UV) irradiation of methylene blue) on plasmid DNA has been analyzed
      by UV spectroscopy, fluorescence spectroscopy, and S1 nuclease digestibility.
      Both native and 1O2-modified plasmid DNA were treated with a number of
      restriction enzymes to map out the sites damaged by 1O2. It was also observed
      that, on exposure to 1O2, native plasmid DNA that is non-immunogenic acquired the
      ability to elicit an immune response in experimental animals. However, the
      induced antibodies exhibited appreciable cross reactivity with various
      polynucleotides and nucleic acids. The data indicate that the antibodies, though
      cross-reactive, preferentially bind 1O2-modified epitopes on plasmid DNA. Gel
      retardation assay further substantiated the enhanced recognition of 1O2-modified
      plasmid DNA over the native form. The antibodies developed were then subjected to
      competition ELISA with sera from various diseases such as systemic lupus
      erythematosus, rheumatoid arthritis, and cancer. These results suggest that upon
      exposure of DNA to 1O2, neo-epitopes are generated, which may be one of the
      factors for the induction of circulating autoantibodies in the three diseases.

PMID- 16978151
TI  - alpha-Defensins from blood leukocytes of the monkey Papio hamadryas.
AB  - Three antimicrobial peptides named PHD1-3 (Papio hamadryas defensin) have been
      isolated from hamadryas baboon blood leukocytes using preparative electrophoresis
      and reverse-phase HPLC. The primary structures of these peptides have been
      determined by automated Edman degradation and mass-spectrometry. The results
      suggest that the peptides belong to the alpha-defensin family. Structural
      homology analysis reveals that among alpha-defensins from other animal species,
      PHD3 is the most closely related to RMAD5 (rhesus macaque alpha-defensin) (90%
      homology) from rhesus macaque leukocytes and also highly similar to human alpha
      defensin HD5 (60% homology), which is produced by intestinal Paneth cells. The
      homology of PHD3 with human neutrophil alpha-defensin HNP1 (human natural
      peptide) was 30%. The primary structures of PHD1 and PHD2 are most similar to
      RED1 (rhesus enteral defensin), one of six enteral alpha-defensins of rhesus
      monkeys. PHD1-3 have been shown to be active against the Gram-positive bacteria
      Listeria monocytogenes and Staphylococcus aureus, the Gram-negative bacterium
      Escherichia coli, and the fungus Candida albicans, similarly to the human HNP1
      defensin.

PMID- 16978152
TI  - Expression of cytochrome P450scc in Escherichia coli cells: intracellular
      location and interaction with bacterial redox proteins.
AB  - Escherichia coli cells producing the mature form of adrenal cytochrome P450scc
      were used as a model for study of cytochrome P450scc topogenesis. By disruption
      of transformed E. coli cells and centrifugation of the homogenate under
      conventional conditions, we obtained membrane and soluble (high-speed
      supernatant) fractions both containing the recombinant protein. Gel-permeation
      high performance liquid chromatography showed that in the high-speed supernatant
      the native cytochrome P450scc exists exclusively as a component of membrane
      fragments exceeding 400 kD. These data supported by kinetic assays suggest that
      the >400-kD particles containing P450scc are lipoprotein associates. In total, we
      failed to detect a genuine soluble cytochrome P450scc in the E. coli cells, which
      suggests that membrane insertion is an obligatory stage of holoenzyme formation.
      In the high-speed supernatant supplemented with NADPH, cytochrome P450scc
      underwent one-electron reduction and could convert 22R-hydroxycholesterol into
      pregnenolone. Thus, we have for the first time observed functional coupling of
      cytochrome P450scc with the bacterial electron transfer system.

PMID- 16978153
TI  - Features of ionogenic group composition in polymeric matrix of lily pollen wall.
AB  - The composition of ionogenic groups and ion-exchange capacity were studied in the
      polymeric matrix of cell walls isolated from the pollen grain and tissues of
      vegetative organs (leaves and stems) of Lilium longiflorum Thunb. The ion
      exchange capacity was evaluated at different pH values and ionic strength of 100
      mM. In the two-layered pollen wall and the somatic cell walls four types of
      ionogenic groups were found: amino groups, two carboxyl groups (represented by
      residues of uronic and hydroxycinnamic acids), and phenolic OH-groups. The groups
      of all four types are present in the intine, whereas the exine contains one type
      of anion-exchange and two types of cation-exchange groups. The contents of each
      type group and their ionization constants were determined. The qualitative and
      quantitative compositions of structural polymers of the pollen intine and somatic
      cell walls are significantly different. It is suggested that hydroxycinnamic
      acids should be involved in cross-linking of polysaccharide chains in both the
      intine and somatic cell primary walls, and such cross-links play a crucial role
      in the structural organization and integrity of the pollen grain wall.

PMID- 16978154
TI  - Modulation of human erythrocyte Ca2+-ATPase activity by glycerol: the role of
      calmodulin.
AB  - The effect of an intracellular cryoprotectant glycerol on human erythrocyte Ca2+
      ATPase activity and possible involvement of calmodulin in the regulation of Ca2+
      pump under these conditions were investigated. The experiments were carried out
      using saponin-permeabilized cells and isolated erythrocyte membrane fractions
      (white ghosts). Addition of rather low concentrations of glycerol to the medium
      increased Ca2+-ATPase activity in the saponin-permeabilized cells; the maximal
      effect was observed at 10% glycerol. Subsequent increase in glycerol
      concentrations above 20% was accompanied by inhibition of Ca2+-ATPase activity.
      Lack of stimulating effect of glycerol on white ghost Ca2+-ATPase may be
      attributed to removal of endogenous compounds regulating activity of this ion
      transport system. Inhibitory analysis using R24571 revealed that activation of
      Ca2+-ATPase by 10% glycerol was observed only in the case of inhibitor
      administration after modification of cells with glycerol; in the case of
      inhibitor addition before erythrocyte contact with glycerol, this phenomenon
      disappeared. These data suggest the possibility of regulation of human
      erythrocyte Ca2+-ATPase by glycerol; this regulatory effect may be attributed to
      both glycerol-induced structural changes in the membrane and also involvement of
      calmodulin in modulation of catalytic activity of the Ca2+-pump.

PMID- 16978155
TI  - Determination of structurally conservative amino acids of the HIV-1 protein gp120
      V3 loop as promising targets for drug design by protein engineering approaches.
AB  - Based on the published NMR spectroscopy data, three-dimensional structures of the
      HIV-1 gp120 protein V3 loop were obtained by computer modeling in the viral
      strains HIV-Haiti and HIV-MN. In both cases, the secondary structure elements and
      conformations of irregular stretches were determined for the fragment
      representing the principal antigenic determinant of the virus, as well as
      determinants of the cellular tropism and syncytium formation. Notwithstanding the
      high variability of the amino acid sequence of gp120 protein, more than 50% of
      the V3 loop residues retained their conformations in the different HIV-1 virions.
      The combined analysis of the findings and the literature data on the biological
      activity of the individual residues of the HIV-1 V3 loop resulted in
      identification of its structurally conservative amino acids, which seem to be
      promising targets for antiviral drug design by protein engineering approaches.

PMID- 16978156
TI  - RNA-protein interactions at the initial and terminal stages of protein
      biosynthesis as investigated by Lev Kisselev (on the occasion of his 70th
      anniversary).
AB  - This review highlights studies by Lev L. Kisselev and his colleagues on the
      initial and terminal stages of protein biosynthesis, which cover the period of
      the last 45 years (1961-2006). They investigated spatial structure of tRNAs,
      structure and functions of aminoacyl-tRNA-synthetases of higher organisms, and
      the final step of protein synthesis, termination of translation. L. Kisselev and
      his team have made three major contributions to these fields of molecular
      biology; (i) they proposed the hypothesis on the role of anticodon triplet of
      tRNA in recognition by cognate aminoacyl-tRNA synthetase, which has been
      experimentally confirmed and is now included in textbooks; (ii) identified
      primary structures and functions of two eukaryotic protein factors (eRF1 and
      eRF3) playing a pivotal role in translation termination; (iii) characterized a
      structural basis for stop codon recognition by eRF1 within the ribosome and
      discovered the negative structural elements of eRF1, limiting its recognition of
      one or two stop-codons.

PMID- 16978157
TI  - Phosphorylation of the proline-rich domain of Xp95 modulates Xp95 interaction
      with partner proteins.
AB  - The mammalian adaptor protein Alix [ALG-2 (apoptosis-linked-gene-2 product)
      interacting protein X] belongs to a conserved family of proteins that have in
      common an N-terminal Bro1 domain and a C-terminal PRD (proline-rich domain), both
      of which mediate partner protein interactions. Following our previous finding
      that Xp95, the Xenopus orthologue of Alix, undergoes a phosphorylation-dependent
      gel mobility shift during progesteroneinduced oocyte meiotic maturation, we
      explored potential regulation of Xp95/Alix by protein phosphorylation in hormone
      induced cell cycle re-entry or M-phase induction. By MALDI-TOF (matrix-assisted
      laser-desorption ionization-time-of-flight) MS analyses and gel mobility-shift
      assays, Xp95 is phosphorylated at multiple sites within the N-terminal half of
      the PRD during Xenopus oocyte maturation, and a similar region in Alix is
      phosphorylated in mitotically arrested but not serum-stimulated mammalian cells.
      By tandem MS, Thr745 within this region, which localizes in a conserved binding
      site to the adaptor protein SETA [SH3 (Src homology 3) domain-containing,
      expressed in tumorigenic astrocytes] CIN85 (a-cyano-4-hydroxycinnamate)/SH3KBP1
      (SH3-domain kinase-binding protein 1), is one of the phosphorylation sites in
      Xp95. Results from GST (glutathione S-transferase)-pull down and peptide
      binding/competition assays further demonstrate that the Thr745 phosphorylation
      inhibits Xp95 interaction with the second SH3 domain of SETA. However,
      immunoprecipitates of Xp95 from extracts of M-phase-arrested mature oocytes
      contained additional partner proteins as compared with immunoprecipitates from
      extracts of G2-arrested immature oocytes. The deubiquitinase AMSH (associated
      molecule with the SH3 domain of signal transducing adaptor molecule) specifically
      interacts with phosphorylated Xp95 in M-phase cell lysates. These findings
      establish that Xp95/Alix is phosphorylated within the PRD during M-phase
      induction, and indicate that the phosphorylation may both positively and
      negatively modulate their interaction with partner proteins.

PMID- 16978158
TI  - Inhaled iloprost in eight heart transplant recipients presenting with post-bypass
      acute right ventricular dysfunction.
AB  - BACKGROUND: During heart transplantation, weaning from cardiopulmonary bypass may
      be particularly laborious as a result of superimposed acute right ventricular
      dysfunction in the setting of pre-existing pulmonary hypertension. Research in
      recent years has focused on inhaled vasodilatory treatment modalities which
      selectively target the pulmonary circulation. METHODS: We present a series of
      eight patients in whom inhaled iloprost, a synthetic prostacyclin analog, was
      used to treat pulmonary hypertension and right ventricular dysfunction detected
      by transesophageal echocardiography during a heart transplant procedure. In
      addition to conventional inotropic support, 20 mug of inhaled iloprost was
      administered via nebulized aerosol for a 20-min period. Complete sets of
      hemodynamic measurements were obtained before inhalation and during and after
      cessation of the inhalation period. RESULTS: Inhaled iloprost decreased the
      transpulmonary gradient at the end of the inhalation period relative to baseline
      (8.2 +/- 1.6 mmHg vs. 11.2 +/- 0.9 mmHg, P < 0.05). The mean pulmonary artery
      pressure to systemic artery pressure ratio decreased over this period (0.24 +/-
      0.07 vs. 0.44 +/- 0.09, P < 0.05). A statistically significant decrease in the
      pulmonary vascular resistance to systemic vascular resistance ratio was also
      observed (0.10 +/- 0.02 vs. 0.19 +/- 0.02, P < 0.05). Improved indices of right
      ventricular function were observed in echocardiographic monitoring. CONCLUSION:
      During heart transplantation procedures, episodes of pulmonary hypertension can
      be successfully treated with inhaled iloprost administration, without untoward
      side-effects or significant systemic impact.

PMID- 16978159
TI  - The effects of pre-operative dexmedetomidine infusion on hemodynamics in patients
      with pulmonary hypertension undergoing mitral valve replacement surgery.
AB  - BACKGROUND: The aim of this study was to investigate the effects of pre-operative
      dexmedetomidine infusion on hemodynamics in patients with pulmonary hypertension
      undergoing mitral valve replacement surgery. METHODS: Patients were randomly
      divided into placebo (group P, n= 16) and dexmedetomidine (group D, n= 16)
      groups. In group D, a 1 microg/kg bolus dose of dexmedetomidine was administered
      10 min before the induction of anesthesia, followed by a 0.4 microg/kg/h infusion
      until the surgical incision. Anesthesia was induced with lidocaine (1 mg/kg),
      midazolam (0.2 mg/kg) and fentanyl (5 microg/kg) in both groups. Anesthesia was
      maintained with 0.5% isoflurane and fentanyl depending on the hemodynamic
      situation. The hemodynamic values during the investigation were obtained.
      RESULTS: In group D, the mean arterial pressure (MAP), mean pulmonary arterial
      pressure (MPAP) and pulmonary capillary wedge pressure (PCWP) were decreased
      effectively in comparison with the values in the placebo group (P < 0.05), and
      there was an attenuation in the increase in the systemic vascular resistance
      index (SVRI) and pulmonary vascular resistance index (PVRI) at the post
      sternotomy period. CONCLUSIONS: The pre-operative administration of the alpha(2)
      agonist dexmedetomidine decreases the fentanyl requirement and attenuates the
      increase in SVRI and PVRI at the post-sternotomy period relative to the baseline
      levels, and decreases effectively MAP, MPAP and PCWP in comparison with the
      values in the placebo group, in patients with pulmonary hypertension undergoing
      mitral valve replacement surgery.

PMID- 16978160
TI  - Post-void residual volume in labor: a prospective study comparing parturients
      with and without epidural analgesia.
AB  - BACKGROUND: This prospective, non-randomized study compared post-void residual
      volume in laboring and postpartum women with or without epidural analgesia.
      METHODS: The study was conducted over 1 year with institutional review board
      approval. Parturients were recruited in early labor and self-selected to either
      the study (with epidural) or control (without epidural) group. Post-void residual
      volume was compared between groups, using transabdominal ultrasound during labor,
      and on postpartum day 1 and 2. Main outcome measure was intrapartum residual
      bladder volume. RESULTS: Thirty patients were recruited to each group. During
      labor, residual bladder volume was significantly larger in the epidural group
      compared with the non-epidural group [median (range)] 240 (12-640), ml vs. 45 (13
      250) ml, respectively, P < 0.001], but was similar on postpartum day 1 and 2.
      Twenty-five (83%) women with epidural analgesia required bladder catheterization
      during labor vs. one (3.3%) without (P < 0.0001). CONCLUSION: The greater post
      void residual volume and increased inability to void in parturients with
      epidurals suggests that epidural analgesia plays a role in intrapartum urinary
      retention.

PMID- 16978161
TI  - Effects of isoflurane, pentobarbital, and urethane on apoptosis and apoptotic
      signal transduction in rat kidney.
AB  - BACKGROUND: Renal cell apoptosis contributes significantly to the pathogenesis of
      acute renal failure. Anesthetic agents have been shown to modulate apoptotic
      signal transduction in various tissues. We examined the effects of 6 h of
      different general anesthetic techniques on renal cell apoptosis in rat kidneys.
      METHODS: Twenty-one male Sprague-Dawley rats were randomly allocated into four
      groups: (i) control, non-anesthetized rats (n= 3) and rats anesthetized with (ii)
      inhaled isoflurane (n= 6), (iii) intraperitoneal pentobarbital (n= 6), and (iv)
      intraperitoneal urethane (n= 6). Animals were sacrificed 6 h after the induction
      of anesthesia. RESULTS: Apoptosis was assessed by terminal deoxynucleotidyl
      transferase-fluorescein end-labeling analysis. RNA was extracted from the left
      kidney to probe cDNA microarrays. Gene expression was measured as a percentage of
      glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and subsequently confirmed using
      reverse transcriptase-polymerase chain reaction (RT-PCR). Compared with the
      control (no anesthesia), urethane significantly (P < 0.001) induced apoptosis in
      both the renal cortex and medulla. Isoflurane significantly (P < 0.001) inhibited
      apoptosis in the medulla. Microarray analysis revealed that urethane up-regulated
      more (74) genes than pentobarbital (16) and isoflurane (10). Isoflurane down
      regulated more genes (85) than pentobarbital (74) and urethane (12). These
      anesthetic-induced modulations were significant (P < 0.05) for 60 isoflurane-, 30
      pentobarbital- and 4 urethane-modulated genes. CONCLUSION: Our results suggest
      that general anesthetic drugs have an effect on renal cell apoptosis and
      apoptotic signal transduction, and thus may potentially affect the risk of
      subsequent acute renal failure.

PMID- 16978162
TI  - Physical education and sport in schools: a review of benefits and outcomes.
AB  - This paper explores the scientific evidence that has been gathered on the
      contributions and benefits of physical education and sport (PES) in schools for
      both children and for educational systems. Research evidence is presented in
      terms of children's development in a number of domains: physical, lifestyle,
      affective, social, and cognitive. The review suggests that PES have the potential
      to make significant and distinctive contributions to development in each of these
      domains. It is suggested that PES have the potential to make distinctive
      contributions to the development of children's fundamental movement skills and
      physical competences, which are necessary precursors of participation in later
      lifestyle and sporting physical activities. They also, when appropriately
      presented, can support the development of social skills and social behaviors,
      self-esteem and proschool attitudes, and, in certain circumstances, academic and
      cognitive development. The review also stresses that many of these benefits will
      not necessarily result from participation, per se; the effects are likely to be
      mediated by the nature of the interactions between students and their teachers,
      parents, and coaches who work with them. Contexts that emphasize positive
      experiences, characterized by enjoyment, diversity, and the engagement of all,
      and that are managed by committed and trained teachers and coaches, and
      supportive and informed parents, significantly influence the character of these
      physical activities and increase the likelihood of realizing the potential
      benefits of participation.

PMID- 16978163
TI  - The joint influence of parental modeling and positive parental concern on
      cigarette smoking in middle and high school students.
AB  - The purpose of the study was to examine the interaction between parental smoking
      status and parental attitudes, as measured by positive parental concern, on the
      risk of adolescent cigarette smoking. Parental smoking and parental concern about
      smoking were measured in a cross-sectional study of 37,244 students, a random
      sample of Maryland middle and high school students, who were current or never
      smokers. Parental concern was classified into 3 levels: strict, moderate, and
      minimal. The likelihood of youths being current smokers was positively associated
      with both parental smoking (both versus neither parent smokes: odds ratio [OR]
      3.4, 95% confidence interval [CI] 3.1-3.7) and parental concern about smoking
      (minimal versus strict concern: OR 2.3, 95% CI 2.1-2.4). Youths with parents who
      did not smoke and with strict concern had the lowest likelihood of smoking. In
      comparison to this group, after adjustment for other social influences the
      likelihood of being a current smoker was more than 5 times greater among boys (OR
      5.8, 95% CI 4.5-7.4) and girls (OR 5.2, 95% CI 4.1-6.5) whose parents both smoked
      and were minimally concerned about smoking. Current smoking in youths was
      independently associated with both parental smoking and less parental concern.
      When these 2 factors were jointly considered, the prevalence of current smoking
      in youths increased both with exposure to parental modeling and reduced parental
      concern about smoking. The results indicate that minimal parental concern about
      smoking worsens the risk due to parental modeling. Parental modeling and parental
      attitudes act synergistically to exacerbate the likelihood of smoking.

PMID- 16978164
TI  - Asthma hospitalization rates among children, and school building conditions, by
      New York State school districts, 1991-2001.
AB  - School-age children spend a significant portion of their day at school where they
      can be exposed to asthma triggers, but little information exists regarding
      potential relationships between childhood asthma and school environmental
      factors. This study examined patterns of asthma hospitalization and possible
      factors contributing to asthma hospitalizations, including sociodemographics and
      school environmental factors, among school-age children (5-18 years) in New York
      State (NYS) over an 11-year period (1991-2001). Asthma hospitalization data from
      the Statewide Planning and Research Cooperative System and the 1990 and 2000
      census population files were geocoded into NYS school districts statewide, and
      school district asthma hospitalization rates were then calculated. Building
      Condition Survey for each school was then utilized to create summary measures of
      school building conditions for each school district. Hospitalization rates were
      linked to district school building conditions by using logistic regression
      analysis that controlled for poverty. Calculation of time trends revealed overall
      declines in asthma rates among school-age children for NYS from 1991 to 2001.
      This general decline was found in each sociodemographic group. The mean rate for
      NYS from 1991 to 2001 was 27/10,000. Poorly rated building systems that were
      significantly associated with increased school district asthma hospitalization
      rates were roofing (odds ratio [OR] = 1.76; 95% confidence interval [CI(95)] =
      1.13-2.74), windows (OR = 1.66; CI(95)= 1.08-2.54), exterior walls (OR = 2.24;
      CI(95)= 1.31-3.83), floor finishes (OR = 1.75; CI(95)= 1.14-2.69), and
      boiler/furnace (OR = 1.71; CI(95)= 1.99-2.94). This does not indicate a definite
      link between these systems and asthma hospitalizations since the available
      building system information is very general and crude.

PMID- 16978165
TI  - An evaluation of an abstinence-only sex education curriculum: an 18-month follow
      up.
AB  - The article examines the results from an 18-month follow-up evaluation of an
      abstinence education curriculum series. Participants were students from 15 school
      districts recruited to participate in the project. The intervention was the Sex
      Can Wait curriculum series, consisting of upper elementary, middle school, and
      high school components. The 5-week curriculum was implemented by teachers who had
      participated in a special teacher training workshop. Both intervention and
      comparison students were surveyed before and after the curriculum intervention
      and at 18-month follow-up. Results indicated short-term effects as follows. Upper
      elementary intervention students indicated higher level of knowledge, more
      hopefulness for the future, and greater self-efficacy than did the comparison
      group. Middle school intervention students did not differ from comparison
      students. High school intervention students reported lower participation rates
      than the comparison group students in sexual intercourse (ever and last month), a
      more positive attitude toward abstinence and a greater intent to remain
      abstinent. Long-term (18 month) benefits were noted as follows: upper elementary
      intervention students had greater knowledge and were less likely than comparison
      students to report participation in sexual intercourse in the last month. Middle
      school intervention students were less likely than comparison students to report
      participation in sexual intercourse ever and sexual intercourse in the last
      month. High school intervention students evidenced greater knowledge and greater
      intent to remain abstinent than did comparison students. Results indicate that
      the program did have some positive benefits that should be considered by those
      interested in abstinence education programming.

PMID- 16978166
TI  - Dating violence victimization: associated drinking and sexual risk behaviors of
      Asian, Native Hawaiian, and Caucasian high school students in Hawaii.
AB  - Ethnic minority groups such as Asian/Pacific Islanders (APIs) and native
      populations in Hawaii are seldom studied in the area of intimate relationships.
      Using the 1999 Hawaii Youth Risk Behavior Survey, this study examined gender and
      ethnic differences in experiencing physical dating violence and whether drinking
      (early initiation, binge drinking), unsafe sexual behaviors (early initiation,
      multiple partners, use of alcohol and drugs with sex, history of sexual abuse),
      and suicidality constitute risk for victimization among APIs, Native Hawaiian
      (NH), and Caucasian high school students in multiethnic state of Hawaii. The
      final analysis included 559 boys and 683 girls. The overall rate of experiencing
      physical violence was 7.8% with both genders reporting similar rates (boys 7.6%,
      girls 8.0%). Although not significantly different, NH students reported a higher
      rate (11.6%) than Caucasians (7.3%) and APIs (6.5%). Significant bivariate
      associations were found between victimization and many of the risk factors.
      Regression analyses indicated that students 16 years or older were nearly 3 times
      more at risk for experiencing dating violence. The risk was 8-fold if youth were
      sexually active by age 13 compared to those who abstained. The risk is 3-fold for
      those who reported prior sexual abuse. Early initiation of drinking (<12 years)
      and suicidality doubled the risk of being a victim. Clearly, the study highlights
      the risk of experiencing dating violence when a teen engages in sex very early or
      uses alcohol. Schools must routinely educate youth about various forms of dating
      violence, the effects of engaging in early sex, and drinking. Screening
      adolescents for associated risk factors such as drinking and depression is
      crucial to identify victimization. Dating violence is an antecedent for adult
      partner violence. Thus, by reducing youth dating violence, we may consequently
      reduce the incidence of adult partner violence.

PMID- 16978167
TI  - Gender, age, and behavior differences in early adolescent worry.
AB  - Early adolescents in the United States are increasingly exposed to a culture of
      worrisome messages. A degree of adolescent worry is normal, but the likelihood of
      a young person being anxious or depressed increases with the perceived number of
      worries. This study examined the effect of age, gender, and worry behavior on
      frequency of 8 adolescent worries. Data were obtained from 1,004 9- to 13-year
      old students visiting 10 health education centers in 7 states. Students responded
      via individual, electronic keypads. Multivariate logistic regression revealed
      that boys worry more about the future, whereas girls worry more about being liked
      or being overweight. The oldest adolescents worry most about their appearance,
      being overweight, their friends, and problems at home. Adolescents who prefer
      talking to parents when worried are less likely to worry about being liked, while
      those who keep worries to themselves have more worries about grades. Those who
      turn to parents for information are less likely to worry about being liked,
      failure, their future, and their friends than those who turn to other sources
      (teachers, Internet, and friends). Recommendations are given to assist health
      educators and other school staff to recognize frequent worriers and plan school
      based approaches to address their needs.

PMID- 16978171
TI  - Quantitative trait loci associated with AutoFOM grading characteristics, carcass
      cuts and chemical body composition during growth of Sus scrofa.
AB  - A three-generation full-sib resource family was constructed by crossing two
      commercial pig lines. Genotypes for 37 molecular markers covering chromosomes
      SSC1, SSC6, SSC7 and SSC13 were obtained for 315 F2 animals of 49 families and
      their parents and grandparents. Phenotypic records of traits including carcass
      characteristics measured by the AutoFOM grading system, dissected carcass cuts
      and meat quality characteristics were recorded at 140 kg slaughter weight.
      Furthermore, phenotypic records on live animals were obtained for chemical
      composition of the empty body, protein and lipid accretion (determined by the
      deuterium dilution technique), daily gain and feed intake during the course of
      growth from 30 to 140 kg body weight. Quantitative trait loci (QTL) detection was
      conducted using least-squares regression interval mapping. Highest significance
      at the 0.1% chromosome-wise level was obtained for five QTL: AutoFOM belly weight
      on SSC1; ham lean-meat weight, percentage of fat of primal cuts and daily feed
      intake between 60 and 90 kg live weight on SSC6; and loin lean-meat weight on
      SSC13. QTL affecting daily gain and protein accretion were found on SSC1 in the
      same region. QTL for protein and lipid content of empty body at 60 kg liveweight
      were located close to the ryanodine receptor 1 (RYR1) locus on SSC6. On SSC13,
      significant QTL for protein accretion and feed conversion ratio were detected
      during growth from 60 to 90 kg. In general, additive genetic effects of alleles
      originating from the Pietrain line were associated with lower fatness and larger
      muscularity as well as lower daily gain and lower protein accretion rates. Most
      of the QTL for carcass characteristics were found on SSC6 and were estimated
      after adjustment for the RYR1 gene. QTL for carcass traits, fatness and growth on
      SSC7 reported in the literature, mainly detected in crosses of commercial lines x
      obese breeds, were not obtained in the present study using crosses of only
      commercial lines, suggesting that these QTL are not segregating in the analysed
      commercial lines.

PMID- 16978172
TI  - Globally dispersed Y chromosomal haplotypes in wild and domestic sheep.
AB  - To date, investigations of genetic diversity and the origins of domestication in
      sheep have utilised autosomal microsatellites and variation in the mitochondrial
      genome. We present the first analysis of both domestic and wild sheep using
      genetic markers residing on the ovine Y chromosome. Analysis of a single
      nucleotide polymorphism (oY1) in the SRY promoter region revealed that allele A
      oY1 was present in all wild bighorn sheep (Ovis canadensis), two subspecies of
      thinhorn sheep (Ovis dalli), European Mouflon (Ovis musimon) and the Barbary
      (Ammontragis lervia). A-oY1 also had the highest frequency (71.4%) within 458
      domestic sheep drawn from 65 breeds sampled from Africa, Asia, Australia, the
      Caribbean, Europe, the Middle East and Central Asia. Sequence analysis of a
      second locus, microsatellite SRYM18, revealed a compound repeat array displaying
      fixed differences, which identified bighorn and thinhorn sheep as distinct from
      the European Mouflon and domestic animals. Combined genotypic data identified 11
      male-specific haplotypes that represented at least two separate lineages.
      Investigation of the geographical distribution of each haplotype revealed that
      one (H6) was both very common and widespread in the global sample of domestic
      breeds. The remaining haplotypes each displayed more restricted and informative
      distributions. For example, H5 was likely founded following the domestication of
      European breeds and was used to trace the recent transportation of animals to
      both the Caribbean and Australia. A high rate of Y chromosomal dispersal appears
      to have taken place during the development of domestic sheep as only 12.9% of the
      total observed variation was partitioned between major geographical regions.

PMID- 16978173
TI  - Comparison of genetic models for analysing the effects of a PvuII polymorphism in
      the oestrogen receptor 1 (ESR1) gene on prolificacy in an Iberian x Meishan pig
      population.
AB  - The effect of a previously reported PvuII polymorphism in oestrogen receptor 1
      (ESR1) was analysed in an F(2) population of Iberian x Meishan pigs. We tested
      three hypotheses: (1) that a causal mutation was fixed in the parental
      populations, (2) that a causal mutation existed that was in complete linkage
      disequilibrium with the alleles of the PvuII polymorphism and (3) that a causal
      mutation existed in linkage disequilibrium within each parental population. The
      third model was the most plausible based on the available data. ESR1 alleles
      displayed different patterns of linkage disequilibrium with the causal mutation
      in each of the parental populations and the PvuII polymorphism was clearly not
      the causal mutation. As a consequence, the use of the ESR1 mutation for selection
      must be evaluated for a particular pig population before it is applied.

PMID- 16978174
TI  - Mitochondrial haplotypes of European wild boars with 2n = 36 are closely related
      to those of European domestic pigs with 2n = 38.
AB  - Wild boars from Western Europe have a 2n = 36 karyotype, in contrast to a
      karyotype of 2n = 38 in wild boars from Central Europe and Asia and in all
      domestic pigs. The phylogenetic status of this wild boar population is unclear,
      and it is not known if it has contributed to pig domestication. We have now
      sequenced the mtDNA control region from 30 European wild boars (22 with a
      confirmed 2n = 36 karyotype) and six Asian wild boars (two Hainan and four
      Dongbei wild boars) to address this question. The results revealed a close
      genetic relationship between mtDNA haplotypes from wild boars with 2n = 36 to
      those from domestic pigs with 2n = 38. Thus, we cannot exclude the possibility
      that wild boars with 2n = 36 may have contributed to pig domestication despite
      the karyotype difference. One of the European wild boars carried an Asian mtDNA
      haplotype, and this most likely reflects gene flow from domestic pigs to European
      wild boars. However, this gene flow does not appear to be extensive because the
      frequency of Asian haplotypes detected among European wild boars (c. 3%) were 10
      fold lower than among European domestic pigs (c. 30%). Previous studies of mtDNA
      haplotypes have indicated that pig populations in Europe and Asia have
      experienced a population expansion, but it is not clear if the expansion occurred
      before or after domestication. The results of the present study are consistent
      with an expansion that primarily occurred prior to domestication because the
      mtDNA haplotypes found in European and Asian wild boars did not form their own
      clusters but were intermingled with haplotypes found in domestic pigs, indicating
      that they originated from the same population expansion.

PMID- 16978175
TI  - Polymorphism at the beta-adrenergic receptor (ADRB3) locus of Merino sheep and
      its association with lamb mortality.
AB  - Beta3-adrenergic receptors are predominantly found on the surface of adipocytes
      and are major mediators of the lipolytic and thermogenic effects of high
      catecholamine concentrations. Recently, variation in the ovine beta3-adrenergic
      receptor (ADRB3) gene has been reported to be associated with lamb survival. In
      this study, polymerase chain reaction-single strand conformational polymorphism
      analysis of part of the ADRB3 intron was used to genotype 4488 Merino lambs born
      at 10 farms throughout the South Island of New Zealand. Univariate and
      multivariate odds ratios for each allele revealed a significant association of
      the E allele with cdd survival and of the D allele with mortality. This variation
      at the ADRB3 locus may assist in the genetic selection for survival in Merino
      sheep.

PMID- 16978176
TI  - Comparison of DNA variants in the PRNP and NF1 regions between bovine spongiform
      encephalopathy and control cattle.
AB  - DNA from 252 bovine spongiform encephalopathy (BSE) cattle and 376 non-diseased
      control cattle were genotyped for nine loci in the prion protein (PRNP) gene
      region, three loci in the neurofibromin 1 (NF1) region and four control loci on
      different chromosomes. The allele and genotype frequencies of the control loci
      were similar in BSE and control cattle. In the analysed 7.4 Mb PRNP region, the
      largest differences between BSE and control cattle were found for the loci REG2,
      R16 and R18, which are located between +300 and +5600 bp, spanning PRNP introns 1
      to 2. Carriers of the REG2 genotype 128/128 were younger at BSE diagnosis than
      those with the other genotypes (128/140 or 140/140). The predominant haplotype
      REG2 128 bp-R18 173 bp occurred more frequently (P < 0.001), and the second-most
      frequent haplotype (REG2 140 bp-R18 175 bp) occurred less frequently (P < 0.05)
      in BSE than in control cattle. The largest frequency differences between BSE and
      control groups were observed in the Brown Swiss breed. Across all breeds, most of
      the same alleles and haplotypes of the PRNP region were associated with BSE. In
      the 23-cM NF1 region, associations with BSE incidence were found for the RM222
      allele and for the DIK4009 genotype frequencies. Cattle carrying RM222 genotypes
      with the 127- or 129-bp alleles were about half a year older at BSE incidence
      than those with other genotypes. Across the breeds, different alleles and
      genotypes of the NF1 region were associated with BSE. The informative DNA markers
      were used to localize the genetic disposition to BSE and may be useful for the
      identification of the causative DNA variants.

PMID- 16978177
TI  - Marker-assisted conservation of European cattle breeds: An evaluation.
AB  - Two methods have been developed for the assessment of conservation priorities on
      the basis of molecular markers. According to the Weitzman approach, contributions
      to genetic diversity are derived from genetic distances between populations.
      Alternatively, diversity within and across populations is optimized by minimizing
      marker-estimated kinships. We have applied, for the first time, both methods to a
      comprehensive data set of 69 European cattle breeds, including all cosmopolitan
      breeds and several local breeds, for which genotypes of 30 microsatellite markers
      in 25-50 animals per breed have been obtained. Both methods were used to
      calculate the gain in diversity if a breed was added to a set of nine non
      endangered breeds. Weitzman-derived diversities were confounded by genetic drift
      in isolated populations, which dominates the genetic distances but does not
      necessarily increase the conservation value of a breed. Marker-estimated kinships
      across populations were less disturbed by genetic drift than the Weitzman
      diversities and assigned high conservation values to Mediterranean breeds, which
      indeed have genetic histories that differ from the non-endangered breeds.
      Prospects and limitations of marker-assisted decisions on conservation priorities
      are discussed.

PMID- 16978178
TI  - Marker-assisted selection based on a multi-trait economic index in chicken:
      Experimental results and simulation.
AB  - A method proposed herein allows simultaneous selection for several production
      traits, taking into consideration their marginal economic values (i.e. the
      economic value of a trait's additional unit). This economic index-marker assisted
      selection (EI-MAS) method is based on the calculation of the predicted economic
      breeding value (BV), using information on DNA markers that have previously been
      found to be associated with relevant quantitative trait loci. Based on the
      proposed method, results with real birds showed that sire progeny performance was
      significantly correlated with expected performance (r = 0.61-0.76; P = 0.03
      0.01). Simulation analysis using a computer program written specifically for this
      purpose suggested that the relative advantage of EI-MAS would be large for traits
      with low heritability values. As expected, the response to EI-MAS was higher when
      the map distance between the marker and the quantitative trait gene was small,
      and vice versa. A large number of distantly located markers, spread 10 cM apart,
      yielded higher response to selection than a small number of closely located
      markers spread 3 cM apart. Additionally, the response to EI-MAS was higher when a
      large number (ca.150) of progeny was used for the prediction equation.

PMID- 16978179
TI  - Mutations in the melanocortin 1 receptor (MC1R) gene are associated with coat
      colours in the domestic rabbit (Oryctolagus cuniculus).
AB  - We sequenced almost the complete coding region of the MC1R gene in several
      domestic rabbits (Oryctolagus cuniculus) and identified four alleles: two wild
      type alleles differing by two synonymous single nucleotide polymorphisms
      (c.333A>G;c.555T>C), one allele with a 30-nucleotide in-frame deletion
      (c.304_333del30) and one allele with a 6-nucleotide in-frame deletion
      (c.280_285del6). A polymerase chain reaction-based protocol was used to
      distinguish the wild-type alleles from the other two alleles in 263 rabbits
      belonging to 37 breeds or strains. All red/fawn/yellow rabbits were homozygous
      for the c.304_333del30 allele. This allele represents the recessive e allele at
      the extension locus identified through pioneering genetic studies in this
      species. All Californian, Checkered, Giant White and New Zealand White rabbits
      were homozygous for allele c.280_285del6, which was also observed in the
      heterozygous condition in a few other breeds. Black coat colour is part of the
      standard colour in Californian and Checkered breeds, in contrast to the two
      albino breeds, Giant White and New Zealand White. Following the nomenclature
      established for the rabbit extension locus, the c.280_285del6 allele, which is
      dominant over c.304_333del30, may be allele E(D) or allele E(S).

PMID- 16978180
TI  - Evidence for biogeographic patterning of mitochondrial DNA sequences in Eastern
      horse populations.
AB  - Equine mitochondrial DNA (mtDNA) phylogeny reconstruction reveals a complex
      pattern of variation unlike that seen in other large domesticates. It is likely
      that this pattern reflects a process of multiple and repeated, although not
      necessarily independent, domestication events. Until now, no clear geographic
      affiliation of clades has been apparent. In this study, amova analyses have
      revealed a significant non-random distribution of the diversity among equine
      populations when seven newly sequenced Eurasian populations were examined in the
      context of previously published sequences. The association of Eastern mtDNA types
      in haplogroup F was highly significant using Fisher's exact test of independence
      (P = 0.00000). For the first time, clear biogeographic partitioning has been
      detected in equine mtDNA sequence.

PMID- 16978181
TI  - Mitochondrial DNA sequence diversity in extant Irish horse populations and in
      ancient horses.
AB  - Equine mitochondrial DNA sequence variation was investigated in three indigenous
      Irish horse populations (Irish Draught Horse, Kerry Bog Pony and Connemara Pony)
      and, for context, in 69 other horse populations. There was no evidence of Irish
      Draught Horse or Connemara Pony sequence clustering, although the majority of
      Irish Draught Horse sequences (47%) were assigned to haplogroup D. Conversely,
      31% of the Kerry Bog Pony sequences were assigned to the rare haplogroup E. In
      addition to the extant population analyses, ancient DNA sequences were generated
      from three out of four Irish archaeological specimens, all of which were assigned
      to haplogroup A.

PMID- 16978182
TI  - Assignment of 117 genes from HSA5 to the porcine IMpRH map and generation of a
      dense human-pig comparative map.
AB  - Twenty-two and eight significant quantitative trait loci for economically
      important traits have been located on porcine chromosomes (SSC) 2q and SSC16
      respectively, both of which have been shown to correspond to human chromosome 5
      (HSA5) by chromosome painting. To provide a comprehensive comparative map for
      efficient selection of candidate genes, we assigned 117 genes from HSA5 using a
      porcine radiation hybrid (IMpRH) panel. Sixty-six genes were assigned to SSC2 and
      48 to SSC16. One gene was suggested to link to SSC2 markers and another to SSC6.
      One gene did not link to any gene, expressed sequence tag or marker in the map,
      including those in the present investigation. This study demonstrated the
      following: (1) SSC2q21-q28 corresponds to the region ranging from 74.0 to 148.2
      Mb on HSA5q13-q32 and the region from 176.0 to 179.3 Mb on HSA5q35; (2) SSC16
      corresponds to the region from 1.4 to 68.7 Mb on HSA5p-q13 and to the region from
      150.4 to 169.1 Mb on HSA5q32-q35 and (3) the conserved synteny between HSA5 and
      SSC2q21-q28 is interrupted by at least two sites and the synteny between HSA5 and
      SSC16 is also interrupted by at least two sites.

PMID- 16978183
TI  - Association of corticotropin-releasing hormone gene variation with performance
      and meat quality traits in commercial pig lines.
AB  - The porcine corticotropin-releasing hormone(CRH) gene is a functional-positional
      candidate for quantitative tract loci on porcine chromosome 4 with major effects
      on growth and carcass composition. In addition, the central role of CRH in the
      neuroendocrine response to stress implicates the CRH gene as a functional
      candidate for meat quality. Association of a single nucleotide polymorphism (SNP)
      in the promoter region of the porcine CRH gene (g.233C > T) with several growth,
      carcass and meat quality traits was examined using more than 2000 individuals
      from four commercial lines: German Landrace (LR), Pietrain (Pi), German Large
      White x German Landrace (F1) and the German commercial fattening pig cross of
      Pietrain x F1 (PiF1). Significant association of the CRH SNP was found with feed
      conversion ratio in the PiF1 line, with carcass length in the LR line and with
      lean content in the F1, LR and Pi lines. Moreover, significant association with
      meat colour was found in the Pi and LR lines; however, the effects were in
      opposite directions. The presented results indicate that sequence variation in
      the porcine CRH gene has no major effect on growth and carcass composition in
      commercial pig lines, although it may significantly contribute to variation in
      meat quality. The g.233C>T SNP may be in incomplete linkage disequilibrium with
      causal mutations and/or exhibit effects in the context of DNA variation at other
      interacting loci.

PMID- 16978184
TI  - A high-resolution comparative radiation hybrid map of equine chromosome 4q12-q22.
AB  - In this study, we present a comprehensive 5000-rad radiation hybrid map of a 40
      cM region on equine chromosome 4 (ECA4) that contains quantitative trait loci for
      equine osteochondrosis. We mapped 29 gene-associated sequence tagged site markers
      using primers designed from equine expressed sequence tags or BAC clones in the
      ECA4q12-q22 region. Three blocks of conserved synteny, showing two chromosomal
      breakpoints, were identified in the segment of ECA4q12-q22. Markers from other
      segments of HSA7q mapped to ECA13p and ECA4p, and a region of HSA7p was
      homologous to ECA13p. Therefore, we have improved the resolution of the human
      equine comparative map, which allows the identification of candidate genes
      underlying traits of interest.

PMID- 16978185
TI  - Genetic analysis of the KIT and MC1R genes in Chinese indigenous pigs with belt
      like coat color phenotypes.

PMID- 16978186
TI  - Elimination of TMC1 and TMIE as candidates for hereditary non-syndromic deafness
      in Dalmatian dogs.

PMID- 16978188
TI  - A gene-based radiation hybrid map of the pig chromosome 6q32 region associated
      with a QTL for fat deposition traits.

PMID- 16978187
TI  - Assessment of SULT1A1, CYP2A6 and CYP2C18 as candidate genes for elevated backfat
      skatole levels in commercial and experimental pig populations.

PMID- 16978189
TI  - Chromosomal assignment of porcine oncogenic and apoptopic genes CACNA2D2, TUSC4,
      ATP2A1, COL1A1, TAC1, BAK1 and CASP9.

PMID- 16978190
TI  - Analysis of a SNP in exon 7 of equine OCA2 and its exclusion as a cause for
      appaloosa spotting.

PMID- 16978191
TI  - Construction and characterization of a BAC library for the European sea bass
      Dicentrarchus labrax.

PMID- 16978192
TI  - Linkage analysis excludes the involvement of the canine PKD2 homologue in bull
      terrier polycystic kidney disease.

PMID- 16978193
TI  - Construction and characterization of a high-resolution, 9000-rad canine radiation
      hybrid panel.

PMID- 16978195
TI  - Interstitial lung disease--the new synergy between radiology and pathology.
AB  - In the last 30 years, high-resolution computed tomography (HRCT) has been the
      major advance in diagnosis of diffuse parenchymal lung disease (DPLD). We review
      the diagnostic accuracy of HRCT and discuss how the gold standard in diagnosis of
      DPLD has shifted from histopathological diagnosis in isolation to a
      multidisciplinary approach. This latter process is now accepted as providing the
      highest levels of diagnostic accuracy in patients with DPLD and lung biopsy is
      primarily reserved for cases with atypical clinical or radiological
      presentations.

PMID- 16978196
TI  - Expression of TCL1 and CD27 in primary cutaneous B-cell lymphomas.
AB  - AIMS: To investigate by immunohistochemical analysis the expression of the TCL1
      oncogene product and of CD27 in 25 cases of primary cutaneous B-cell lymphomas
      (PCBCL) classified according to the World Health Organization-European
      Organization for Research and Treatment of Cancer classification of cutaneous
      lymphomas. In B-cell ontogenesis TCL1 is mainly expressed by 'naive' B
      lymphocytes and by a subset of germinal centre B cells, whereas CD27 is expressed
      by a subset of germinal centre B cells, 'memory' B lymphocytes and plasma cells,
      suggesting that their expression in physiological conditions is mutually
      exclusive. METHODS AND RESULTS: Overall, TCL1 was expressed in 5/25 cases (20%)
      and CD27 in 15/25 cases (60%). Furthermore, 7/25 cases (28%) were TCL1- and CD27-
      and 2/25 cases (8%) were TCL1+ and CD27+. In particular, primary cutaneous
      follicle-centre lymphomas (10 cases) showed a variable expression of both TCL1
      and CD27, whereas primary cutaneous marginal-zone B-cell lymphomas (eight cases)
      showed, with the exception of a single case, a definite CD27+/TCL1- profile.
      CONCLUSIONS: These findings indicate: (i) the TCL1 oncogene product is uncommonly
      expressed in PCBCL (20% of cases, mainly of the follicle-centre subtype); (ii) in
      contrast, CD27 is often expressed in PCBCL (60% of cases), mainly of the marginal
      zone subtype; (iii) the coexpression of TCL1 and CD27 may be seldom observed in
      PCBCL (8% of cases); (iv) PCBCL does not seem to show, in terms of either TCL1 or
      CD27 expression, significant differences compared with its systemic counterparts.

PMID- 16978198
TI  - Synovitis score: discrimination between chronic low-grade and high-grade
      synovitis.
AB  - AIMS: To standardize the histopathological assessment of synovial membrane
      specimens in order to contribute to the diagnostics of rheumatic and non
      rheumatic joint diseases. METHODS AND RESULTS: Three features of chronic
      synovitis (enlargement of lining cell layer, cellular density of synovial stroma,
      leukocytic infiltrate) were semiquantitatively evaluated (from 0, absent to 3,
      strong) and each feature was graded separately. The sum provided the synovitis
      score, which was interpreted as follows: 0-1, no synovitis; 2-4, low-grade
      synovitis; 5-9, high-grade synovitis. Five hundred and fifty-nine synovectomy
      specimens were graded by two independent observers. Clinical diagnoses were
      osteoarthrosis (n=212), post-traumatic arthritis (n=21), rheumatoid arthritis
      (n=246), psoriatic arthritis (n=22), reactive arthritis (n=9), as well as
      controls (n=49) from autopsies of patients without joint damage. Median synovitis
      scores when correlated with clinical diagnoses were: controls 1.0, osteoarthritis
      2.0, post-traumatic arthritis 2.0, psoriatic arthritis 3.5, reactive arthritis
      5.0 and rheumatoid arthritis 5.0. The scores differed significantly between most
      disease groups, especially between degenerative and rheumatic diseases. A high
      grade synovitis was strongly associated with rheumatic joint diseases (P<0.001,
      sensitivity 61.7%, specificity 96.1%). The correlation between the two observers
      was high (r=0.941). CONCLUSION: The proposed synovitis score is based on well
      defined, reproducible histopathological criteria and may contribute to diagnosis
      in rheumatic and non-rheumatic joint diseases.

PMID- 16978197
TI  - Cytoplasmic localization of p63 is associated with poor patient survival in lung
      adenocarcinoma.
AB  - AIMS: To determine the significance of p63 protein expression in the development
      and progression of lung adenocarcinoma. METHODS AND RESULTS: The expression of
      p63 was immunohistochemically investigated in 92 cases of lung adenocarcinoma
      with a maximum diameter of 30 mm or less. p63 expression was observed not only in
      the nuclei (46/92 cases, 50%), but also in the cytoplasm of neoplastic cells
      (47/92, 51%). Nuclear localization of p63 was correlated with nuclear
      accumulation of p53 (P=0.0120), whereas the presence of nuclear p63 had no
      apparent effect on patient survival. Cytoplasmic localization of p63 was found to
      be correlated with shorter survival periods by univariate and multivariate
      analyses (P=0.0486 and P=0.0488, respectively) and the relation was independent
      of clinicopathological factors. Cytoplasmic localization of p63 was further
      confirmed by immunoblots of the cytoplasmic fraction of HLC-1, a lung
      adenocarcinoma cell line which predominately expressed DeltaNp63alpha transcript
      relative to TAp63 transcript by quantitative reverse transcriptase-polymerase
      chain reaction. CONCLUSIONS: Cytoplasmic expression of p63 is an adverse
      prognostic factor in patients with adenocarcinoma of the lung.

PMID- 16978199
TI  - Cytokeratin profiles of male breast cancers.
AB  - AIMS: The prognostic factors and expression of molecular markers in male breast
      carcinomas are similar to those in female breast cancers. The identification of
      distinct cytokeratin (CK) profiles (basal as opposed to luminal cells) helps to
      identify subsets of tumours with different clinical behaviour. The aim of this
      study was to investigate CK expression in male breast cancer. METHODS AND
      RESULTS: Thirty-two cases of male breast cancer were studied. The panel of CKs
      studied by immunohistochemistry included: 5/6, 14, 17, 18 and 19. Pathological
      findings and CK expression were analysed in all cases. Histological patterns
      included ductal carcinoma in situ, invasive ductal carcinoma and mixed patterns.
      Four cases were positive for CK5/6 and CK14, identifying a basal-like phenotype.
      CK17 was negative in all but two cases. All cases expressing either CK5/6 or CK14
      were invasive carcinomas of high nuclear and histological grade and were also
      larger compared with the tumours not expressing CK5/6 and CK14. All tumours
      except three (also negative for CK5/6) expressed CK18 and CK19. The four basal
      like tumours were negative for Her-2 expression. CONCLUSIONS: Male breast
      carcinomas have a basal-like phenotype that is similar in frequency to that of
      female breast carcinomas. The expression of CK5/6 and CK14 identifies a subset of
      pathologically aggressive male breast cancers.

PMID- 16978200
TI  - Transforming growth factor-beta pathway disruption and infiltration of colorectal
      cancers by intraepithelial lymphocytes.
AB  - AIMS: Colorectal cancers deficient in DNA mismatch repair (MMR) are often
      characterized by the presence of numerous intraepithelial lymphocytes (IELs).
      These CD8+ T cells selectively express CD103, which is upregulated locally by
      transforming growth factor (TGF)-beta, and adhere to E-cadherin expressed by
      mucosal epithelia. Many of these cancers also possess inactivating mutations in
      the type II TGF-beta receptor and are believed to be insensitive to TGF-beta. The
      present study aimed to explore whether such refractoriness to TGF-beta is an
      independently contributing factor to IEL retention. METHODS AND RESULTS: A panel
      of colorectal cancers enriched for DNA MMR deficiency was examined by
      immunohistochemistry to explore the expression levels and localization of various
      components in the TGF-beta signalling pathway. Logistic regression was then
      carried out in order to identify predictors of elevated lymphocytic infiltration
      independent of DNA MMR status. Increases in Smad4 expression, tumour cell
      proliferation and TGF-beta secretion each emerged as independent predictors of
      marked lymphocyte infiltration. CONCLUSIONS: These results strongly support the
      hypothesis that refractoriness to normal TGF-beta signalling in colorectal
      cancers plays a role in the retention of lymphocytes within tumour epithelium.
      Since IEL infiltration is an independent predictor of favourable prognosis, the
      TGF-beta pathway may represent an important therapeutic target.

PMID- 16978202
TI  - Increasing EMMPRIN and matriptase expression in hepatocellular carcinoma: tissue
      microarray analysis of immunohistochemical scores with clinicopathological
      parameters.
AB  - AIMS: To examine the expression of extracellular matrix metalloprotease inducer
      (EMMPRIN) and matriptase in hepatocellular carcinoma (HCC) and to correlate this
      with tumour progression. METHODS AND RESULTS: Immunohistochemical analysis of
      EMMPRIN and matriptase was performed on tissue microarrays of 122 cases of HCC
      with various histological grades and/or clinical parameters. The expression of
      EMMPRIN and matriptase was undetectable in normal liver parenchyma of all eight
      control cases. However, among the 122 HCC cases, EMMPRIN and matriptase
      immunoreactivity was seen on the cell membrane and in the cytoplasm. The average
      immunostaining scores of EMMPRIN were 88 for grade I HCC, 195 for grade II HCC
      and 293 for grade III HCC. Of 85 HCC cases in 122 with detailed clinical TNM
      stages, the average immunostaining scores of EMMPRIN were 75 for stage T1, 177
      for stage T2, 260 for stage T3 and 313 for stage T4 cases of HCC. In addition,
      the average immunostaining scores of matriptase were 84 for grade I HCC, 187 for
      grade II HCC, 302 for grade III HCC, and 72 for stage T1, 181 for stage T2, 224
      for stage T3 and 284 for stage T4 cases of HCC. More advanced M and N stages of
      HCC were associated with higher intensity, greater percentages of tumour staining
      and immunostaining scores of EMMPRIN and matriptase. Higher EMMPRIN and
      matriptase immunostaining scores in HCCs also correlated significantly with
      tumour grading and TNM stages. CONCLUSIONS: Our findings demonstrate for the
      first time that EMMPRIN and matriptase are overexpressed in HCC. These may be
      novel biomarkers for the diagnosis and treatment of HCC.

PMID- 16978201
TI  - CDX-2 expression in pseudomyxoma peritonei: a clinicopathological study of 42
      cases.
AB  - AIMS: CDX-2 is a highly sensitive and specific marker of intestinal epithelial
      cells and their neoplastic counterparts. CDX-2 status in pseudomyxoma peritonei
      (PMP) has been barely reported. The aim of this study was to investigate the
      clinicopathological features of 42 cases of PMP with a special emphasis on CDX-2.
      METHODS AND RESULTS: All patients were treated by cytoreduction.
      Immunohistochemistry was performed for CDX-2, MUC-2, MUC-5AC, cytokeratin (CK) 7
      and CK20. Statistical correlation was evaluated for age, sex, completeness of
      cytoreduction and histological subtype with overall and progression-free survival
      (OS and PFS). PMP consisted of 32 cases of disseminated peritoneal adenomucinosis
      and 10 cases of peritoneal mucinous carcinomatosis. The appendix evaluated in 25
      cases showed two mucinous adenocarcinomas and 21 low-grade appendiceal mucinous
      neoplasms. CDX-2 was diffusely positive in 40 cases, with the remaining two cases
      being focally positive. All cases demonstrated diffuse reactions to CK20 and MUC
      2, and variable reactions to MUC-5AC, while CK7 was variably positive in 38
      cases. Five-year OS was 97%. Histological type was significantly correlated with
      PFS (P=0.02). CONCLUSIONS: CDX-2 is diffusely and strongly positive in PMP. This
      is a useful marker to confirm an appendiceal origin of PMP, particularly when
      used in conjunction with CK7, CK20, MUC-2 and MUC-5AC.

PMID- 16978203
TI  - Pathology of fungal infections of the central nervous system: 17 years'
      experience from Southern India.
AB  - AIMS: To describe the pathology of central nervous system (CNS) fungal infections
      with particular reference to India. METHODS AND RESULTS: This was a retrospective
      study from 1988 to 2004 constituting 130 cases. The diagnosis was based on
      morphology of biopsy/autopsy material. These included aspergillosis (n=73),
      zygomycosis (n=40), cryptococcosis (n=2), rhodotorulosis (n=1), candidiasis
      (n=5), maduramycosis (n=1), pheohyphomycosis (n=3) and mixed infections (n=5).
      Predisposing risk factors were present in 49 (38%) patients only. The majority of
      the patients were immunocompetent. The commonest risk factor was diabetes
      mellitus, the commonest route of infection was from a contiguous site and the
      commonest pathology was granuloma. Culture positivity was seen in only 31%.
      CONCLUSION: Environmental factors in tropical countries such as India play a
      significant role in the pathogenesis of CNS fungal infections.

PMID- 16978204
TI  - Quantification of immunohistochemistry--issues concerning methods, utility and
      semiquantitative assessment I.
AB  - Immunohistochemistry is no longer a technique used only for research but is
      employed increasingly for diagnosis and for the assessment of therapeutic
      biomarkers. The latter, in particular, often require a semiquantitative
      evaluation of the extent of their presence. There are many factors that can
      affect this that relate to the method: fixation of tissue, duration and type of
      antigen retrieval, antibody specificity, antibody dilution and detection systems.
      Other complexities relate to assessment. Different scoring systems are used for
      either the same or different antigens. Cut-off levels for assessing whether a
      tissue is 'positive' or 'negative' can vary for the same antigen. Whilst there
      are quality assurance schemes for the methodology that have improved standards of
      staining, there are no similar schemes that relate to interpretation, although
      errors here can create as many problems. There have been improvements in
      automated analysis but availability is limited and it is still predominantly a
      research tool. In order for quantification of immunohistochemistry to be a
      reliable and reputable tool, there must be easy to use, reproducible,
      standardized protocols for assessment which are international. Improvements in
      automated analysis with wider applicability could lead to standardization.

PMID- 16978205
TI  - Quantification of immunohistochemistry--issues concerning methods, utility and
      semiquantitative assessment II.
AB  - Immunohistochemistry is entering its fourth decade of use on formalin-fixed
      paraffin-embedded tissues. Over this period the method has evolved to become a
      major part of the practice of diagnostic surgical pathology worldwide. From the
      beginning immunohistochemistry has been adapted to provide a range of markers of
      cell lineage and tissue type, with particular application to the diagnosis and
      classification of tumours. In this modality immunohistochemical methods were
      employed simply as 'special stains', the results of which were evaluated
      qualitatively by the pathologist, as for any other stain. More recently,
      attention has shifted to the demonstration of prognostic markers in tumour cells,
      driven by the advent of molecular biology and the discovery of numerous
      regulatory molecules, coupled with manufacture of the corresponding specific
      antibodies. Immunohistochemistry has rapidly adapted to this new use, but in so
      doing the demand for quantification has become paramount; it is no longer enough
      that the 'stain' is there; rather it is a question of 'How much is there?'. This
      review explores the limitations of immunohistochemistry when employed in a
      semiquantitative mode, and explores the possibility of fulfilling the full
      potential of immunohistochemistry, as a true quantitative immunoassay applied in
      a tissue section environment.

PMID- 16978207
TI  - Florid marginal zone differentiation in follicular lymphoma mimicking marginal
      zone lymphoma of MALT type in the lung.

PMID- 16978208
TI  - Omental deposits of fetal parts as a sequal to salpingectomy for ruptured ectopic
      pregnancy.

PMID- 16978209
TI  - Immunohistochemical detection of protein kinase C-beta (PKC-beta) in tumour
      specimens of patients with non-small cell lung cancer.

PMID- 16978210
TI  - Primary follicular dendritic cell sarcoma of the lung.

PMID- 16978211
TI  - Distribution of DC-SIGN dendritic cells in the lymphoid stroma of Warthin's
      tumour; immunohistochemical analysis.

PMID- 16978212
TI  - Serosal involvement in colorectal carcinoma.

PMID- 16978213
TI  - A colonic polyp due to Langerhans cell histiocytosis: a lesion not to be confused
      with metastatic malignant melanoma.

PMID- 16978214
TI  - Angioinvasive aspergillosis presenting as neutropenic colitis.

PMID- 16978215
TI  - Transcription factor AP-2 is expressed in human Schwann cell-derived tumours.

PMID- 16978216
TI  - Myxoid solitary fibrous tumour of the meninges: case report.

PMID- 16978218
TI  - Bone marrow may be a reservoir of long-lived memory T cells specific for minor
      histocompatibility antigen.

PMID- 16978219
TI  - Rituximab failure in a patient with allo-FVIII inhibitor.

PMID- 16978220
TI  - Natural pregnancy and delivery after allogeneic bone marrow transplantation in a
      Fanconi anaemia patient.

PMID- 16978221
TI  - Reduced-intensity conditioning allogeneic stem cell transplantation for patients
      with chemoresistant or relapsed follicular lymphoma.

PMID- 16978222
TI  - Exisulind induces apoptosis in advanced myelodysplastic syndrome (MDS) and acute
      myeloid leukaemia/MDS.
AB  - The influence of Exisulind on the viability and apoptosis of CD34(+) stem cells
      from patients with advanced myelodysplastic syndrome (MDS) and acute myeloid
      leukaemia (AML)/MDS was investigated. In eight out of 10 patient samples
      Exisulind reduced the fraction of viable cells by inducing apoptosis. We found
      evidence that Exisulind-mediated apoptosis depends on c-Jun NH(2)-terminal kinase
      (JNK) activation. Addition of a specific JNK-inhibitor to Exisulind-treated
      advanced MDS and AML/MDS cells partly abrogated apoptosis. We propose that
      Exisulind is tested in clinical phase I/II trials for the treatment of advanced
      MDS and AML/MDS.

PMID- 16978224
TI  - Repeat sentinel lymph node procedure in vulval carcinoma.

PMID- 16978223
TI  - Clinical implications of SOCS1 methylation in myelodysplastic syndrome.
AB  - The suppressor of cytokine signalling-1 (SOCS1) protein is a tumour suppressor.
      Hypermethylation of SOCS1 gene, resulting in transcriptional silencing, is
      suggested to play an important role in cancer development. We sought to
      characterise SOCS1 methylation in primary myelodysplastic syndrome (MDS) and
      clarify its clinical implications. The methylation status of SOCS1 was analysed
      by methylation-specific polymerase chain reaction in 114 patients with primary
      MDS and serial studies were performed in 29 of them. SOCS1 methylation occurred
      in 54 patients (47.4%), and was more frequent in patients with high-risk MDS than
      in those with low-risk (52.6% vs. 25.8%, P = 0.011). SOCS1 methylation was
      closely associated with NRAS mutation (P = 0.010) and inversely associated with
      good-risk karyotype (P = 0.021). With a median follow-up of 17 months (range: 1
      231 months), two patients acquired SOCS1 methylation during disease progression.
      In two patients, SOCS1 methylation present at diagnosis, disappeared after
      haematopoietic stem cell transplantation. Patients with SOCS1 methylation had a
      higher cumulative risk of leukaemic transformation than those without (55.8% vs.
      27.7% at 3 years, P = 0.004). This difference remained significant within the
      subgroup of patients with high-risk MDS (67.3% vs. 45.1% at 3 years, P = 0.045).
      This is the first report to demonstrate the clinical relevance of SOCS1
      methylation in MDS. It may play an important role in the pathogenesis of MDS,
      especially among patients with high-risk subtypes.

PMID- 16978225
TI  - Prediction of recurrence after treatment for high-grade cervical intraepithelial
      neoplasia: the role of human papillomavirus testing and age at conisation.
AB  - OBJECTIVES: The aim of this study was to examine the accuracy of the presence of
      high-risk human papillomavirus (HR-HPV) DNA (HR-HPV DNA test) postconisation as
      prediction of recurrent or residual cervical intraepithelial neoplasia (CIN)
      after treatment of high-grade cervical intraepithelial lesions (CIN2+) in a
      prospective study and to compare this with follow-up cytology and the marginal
      status of the excised tissue. DESIGN: Prospective follow-up study. SETTING:
      Unselected women presenting at colposcopy clinic of University Hospital
      Gasthuisberg, Leuven. POPULATION: Seventy-two women treated with conisation for
      CIN2 or CIN3. METHODS: Women were followed by HR-HPV DNA test (Hybrid Capture II
      test of Digene) every 3 to 6 months. The same vial was used for cytology and the
      HR-HPV DNA test (SurePath). All women were further followed by colposcopy and
      cytology for 24 months at 6-month intervals. The outcome of the study was
      presence of >CIN2, proven with colposcopy-directed biopsy occurring within 24
      months after treatment. HR-HPV status was correlated with recurrent or residual
      CIN2+. MAIN OUTCOME MEASURES: Sensitivity, specificity, predictive values and
      diagnostic odds ratios to predict treatment failure or cure were computed for HR
      HPV testing, marginal status and follow-up cytology. HR-HPV status was also
      correlated with section margins postconisation and with the first cervical smear.
      RESULTS: In 6 of the 72 treated women (8%), residual or recurrent CIN occurred.
      Women with recurrence were significantly older than women without a recurrence
      (51.5 +/- 9.6 versus 39.8 +/- 12.2 years, P= 0.007). All six women with
      recurrence were HR-HPV positive, four had a positive follow-up smear
      (>or=atypical squamous cells of uncertain significance = ASCUS+) and only two had
      involved section margins. Among the 66 cured women, 15 were HR-HPV positive, 6
      had an abnormal smear and 12 had positive section margins. Sensitivity of
      cytology, positive section margins and HR-HPV DNA positivity was 66.7, 33.3 and
      100% to predict treatment failure. Specificity of the three tests was,
      respectively, 90.9, 81.8 and 77.3%. Women with HR-HPV DNA at 3 to 6 months showed
      recurrent or residual CIN in 15% (2/13) if they had normal follow-up Pap smears
      and in 50% (4/8) if they had abnormal Pap smears. Margin status was not
      statistically significantly associated with human papillomavirus status.
      CONCLUSION: Persistence or clearance of HR-HPV DNA is an early valid prognostic
      marker of failure or cure after treatment for CIN2+ and is more accurate than
      cytology or section margin status at the time of conisation. The absence of HR
      HPV DNA has a 100% negative predictive value. Higher age at conisation may be a
      previously unrecognised risk factor for recurrence.

PMID- 16978226
TI  - The effect of learning curve on the outcome of caesarean section.
AB  - OBJECTIVE: To evaluate the operative outcomes when trainees first perform
      caesarean sections independently. DESIGN: A retrospective study in a tertiary
      obstetric unit. POPULATION: Five hundred caesarean sections, which represented
      the first 50 caesarean sections performed independently by each of ten trainees,
      were studied. METHODS: The effect of learning curve on outcome was analysed. MAIN
      OUTCOME MEASURES: Total operative time, incision-to-delivery interval, operative
      blood loss, Apgar score, cord arterial pH, incidence of neonatal intensive care
      unit admission, postoperative complication rates and duration of hospitalisation.
      RESULTS: The mean operative time for the first five cases by trainees was 52.2 +/
      11.4 minutes. It progressively decreased and reached 39.6 +/- 8.4 minutes for
      the 46th to 50th cases. The operative time was significantly longer in the first
      15 caesarean sections (P < 0.05). Moreover, the incision-to-delivery interval was
      also longer during the first five cases (P= 0.02). Besides the time of the
      operation, the trend for operative blood loss stabilised after the first ten
      caesarean sections (P < 0.05). Otherwise, there were no significant differences
      among other outcome variables. CONCLUSION: This study shows that trainees need to
      perform 10-15 caesarean sections before their skills become more proficient.
      Senior obstetricians may need to provide guidance to the trainees during their
      first independent 15 caesarean sections.

PMID- 16978228
TI  - Uterine rupture and labour after a previous low transverse caesarean section.

PMID- 16978229
TI  - The advent of international 'mail-order' egg donation.
AB  - The rising demand and increasing scarcity of donor oocytes in developed countries
      have led to some fertility clinics sourcing oocyte donors from abroad,
      particularly from poorer countries, in what is referred to as 'transnational' or
      'international' oocyte donation. In a further new 'twist' to this scheme, frozen
      sperm of the recipient's male partner is exported abroad through courier mail and
      is used to fertilise donor oocytes in a foreign clinic to produce embryos, which
      are then cryopreserved and imported back by mail for transfer to the woman. There
      are numerous ethical concerns with regards to such means of procuring donor
      oocytes. First, there is an issue of exploiting economically underprivileged
      women in poorer countries and disproportionate gains on the part of medical
      doctors and fertility clinics. Second, there is a question of abdication of
      responsibility for the donor's welfare on the part of the fertility doctor who
      takes charge of the recipient's treatment abroad if oocyte donors were to develop
      severe ovarian hyperstimulation syndrome. Third, the issue of responsibility and
      accountability becomes even more contentious if congenital defects were to appear
      in offsprings born from transnational oocyte donation or in the case of
      transmission of communicable diseases such as hepatitis B, syphilis and AIDS to
      the recipient. Last, cost savings from the lower prescription price of fertility
      drugs in economically less-developed countries may not be passed down to the
      oocyte recipient but instead be exploited to boost the already substantial profit
      margin of fertility clinics and doctors.

PMID- 16978230
TI  - Uterine blood flow during supine rest and exercise after 28 weeks of gestation.
AB  - OBJECTIVE: To test the null hypothesis that, after 28 weeks of gestation, uterine
      blood flow during supine rest and supine exercise is no different than uterine
      blood flow at left-lateral rest. DESIGN: In vivo experimental study in pregnant
      women. SETTING: Department of Obstetrics, MetroHealth Medical Center, Cleveland,
      OH, USA. POPULATION: Fourteen, physically active, late-pregnant women who
      continued supine exercise throughout gestation. METHODS: Studies were carried out
      between 29 and 38 weeks of gestation. Maternal blood pressure, maternal heart
      rate, and ultrasound estimates of volume blood flow in the right ascending branch
      of the uterine artery were obtained serially at rest in the left-lateral
      position, at rest in the supine position, during and immediately after 10 minutes
      of supine exercise, and again at rest in the left-lateral position. Exercise
      sessions included alternating 60- to 90-second periods of abdominal crunches and
      leg exercise at moderate/high intensity (Borg's rating of perceived exertion 14
      +/- 1). MAIN OUTCOME MEASURES: Blood pressure, heart rate, and uterine artery
      volume flow. RESULTS: Data are presented as the mean +/- SD. Maternal heart rate
      and blood pressure were unchanged at supine rest but increased during supine
      exercise (heart rate increased from 76 +/- 9 to 98 +/- 12 beats per minute, mean
      arterial pressure increased from 81 +/- 6 to 102 +/- 12 mmHg). Volume flow fell
      from 410 +/- 93 to 267 +/- 73 cc/minute after 5 minutes of supine rest and then,
      during supine exercise, increased to 355 +/- 125 cc/minute. Uterine artery
      luminal diameter and blood flow correlated directly with tissue weights at birth
      (r(2) values between 0.32 and 0.59). CONCLUSIONS: In physically active women,
      uterine blood flow decreases during both supine rest and supine exercise but the
      decrease in the former is twice that seen in the latter.

PMID- 16978232
TI  - A comparison of perinatal mortality in Korea on holidays and working days.
AB  - OBJECTIVE: To examine whether the perinatal mortality of infants born during
      holidays differs from that of infants born on workdays, and to elucidate its
      cause. DESIGN: Cross-sectional study. Setting Vital statistics linked to the
      National Infant Mortality Survey data for 1999 births in Korea. POPULATION: In
      all, 628 485 births in 1999 in Korea. METHODS: Number of births and perinatal
      mortality were classified according to the day of the week using the occurrence
      index. After adjusting for confounding factors, the odds ratios (ORs) for
      increased holiday mortality were estimated using logistic regression. MAIN
      OUTCOME MEASURE: Birthweight-adjusted perinatal mortality. RESULTS: Births on
      holidays were 33% fewer and perinatal deaths 24% higher than expected (PMR,
      Perinatal Mortality Rate, 16.4 versus 12.8; OR, 1.3; 95% CI, 1.2-1.4). After the
      adjustment of birthweight, gender, plurality and congenital anomalies, the odds
      ratio for death of infants born during holidays was 1.2 (95% CI, 1.1-1.3).
      CONCLUSIONS: The higher perinatal mortality during holidays in Korea appears to
      be due to different qualities of perinatal care, rather than difference in case
      mix.

PMID- 16978233
TI  - Multicentre, parallel group, randomised, single-blind study of the safety and
      efficacy of atosiban versus ritodrine in the treatment of acute preterm labour in
      Korean women.
AB  - OBJECTIVE: To compare the efficacy and safety of atosiban with those of ritodrine
      in preterm labour. DESIGN: Multicentre, single-blind, randomised, controlled
      trial. SETTING: Obstetric units in six referral centres in Korea. POPULATION:
      Women with singleton pregnancies with preterm labour, between 24 and 33 + 6 weeks
      of gestation. METHODS: One hundred and twenty-eight women were randomised to
      receive intravenous atosiban (n= 63) or ritodrine (n= 65) and were stratified by
      gestational age (<28 weeks and >or=28 weeks). Atosiban or ritodrine was
      administered for up to 48 hours. Progression of labour was assessed by the
      frequency of contractions and cervical dilatation and effacement. Alternative
      tocolysis could be given as rescue therapy. MAIN OUTCOME MEASURE: Efficacy was
      assessed as the proportion of women in each group who did not deliver and did not
      need alternative tocolytic therapy at 48 hours and 7 days after therapy
      initiation. Safety was assessed as the numbers of maternal adverse events and
      neonatal morbidity. RESULTS: Tocolytic efficacy after 7 days was significantly
      better in the atosiban group than in the ritodrine group (60.3 versus 34.9%), but
      not at 48 hours (68.3 versus 58.7%). Maternal adverse events related to therapy
      were reported less frequently in the atosiban group (7.9 vs 70.8%; P= 0.0001),
      resulting in fewer early drug terminations due to adverse events (0 versus 20.0%;
      P= 0.0001). This, however, was not accompanied by a concurrent improvement in
      perinatal outcomes. CONCLUSION: The efficacy and safety of atosiban in the
      treatment of preterm labour were superior to those of ritodrine.

PMID- 16978234
TI  - Murine splenocytes produce inflammatory cytokines in a MyD88-dependent response
      to Bacillus anthracis spores.
AB  - Bacillus anthracis is a sporulating Gram-positive bacterium that causes the
      disease anthrax. The highly stable spore is the infectious form of the bacterium
      that first interacts with the prospective host, and thus the interaction between
      the host and spore is vital to the development of disease. We focused our study
      on the response of murine splenocytes to the B. anthracis spore by using
      paraformaldehyde-inactivated spores (FIS), a treatment that prevents germination
      and production of products associated with vegetative bacilli. We found that
      murine splenocytes produce IL-12 and IFN-gamma in response to FIS. The IL-12 was
      secreted by CD11b cells, which functioned to induce the production of IFN-gamma
      by CD49b (DX5) NK cells. The production of these cytokines by splenocytes was not
      dependent on TLR2, TLR4, TLR9, Nod1, or Nod2; however, it was dependent on the
      signalling adapter protein MyD88. Unlike splenocytes, Nod1- and Nod2-transfected
      HEK cells were activated by FIS. Both IL-12 and IFN-gamma secretion were
      inhibited by treatment with B. anthracis lethal toxin. These observations suggest
      that the innate immune system recognizes spores with a MyD88-dependent receptor
      (or receptors) and responds by secreting inflammatory cytokines, which may
      ultimately aid in resisting infection.

PMID- 16978236
TI  - Molecular genetic analysis of a variant Bernard-Soulier syndrome due to compound
      heterozygosity for two novel glycoprotein Ibbeta mutations.
AB  - Bernard-Soulier syndrome (BSS) is a rare bleeding disorder characterized by giant
      platelets, thrombocytopenia, and prolonged bleeding time. It is caused by
      abnormalities in the glycoprotein (GP) Ib/IX/V complex, the receptor for von
      Willebrand factor (vWF). Most cases of BSS described so far involve quantitative
      rather than qualitative defects in the complex. In this study, we investigated
      the effects of two naturally occurring mutations in the GPIbbeta gene, C122S and
      443delG, on the expression of the GPIb/IX complex identified in a variant type of
      BSS in which the platelets had severely reduced GPIbalpha ( approximately 10%)
      and less markedly reduced GPIbbeta and GPIX ( approximately 20%) expression.
      Immunoblot analysis showed the absence of non-reduced GPIb (GPIbalpha/GPIbbeta)
      in the patient's platelets. Transient transfection experiments in 293T cells
      revealed the expression of GPIbbeta Ser122 polypeptide and absence of GPIbbeta
      443delG polypeptide. Although no disulfide-linked association was observed
      between GPIbbeta Ser122 and GPIbalpha, GPIbbeta Ser122 was non-covalently
      associated with both GPIbalpha and GPIX subunits on the cell surface when
      cotransfected with wild-type GPIbalpha and GPIX. Chinese hamster ovary cells
      stably expressing GPIbalpha/Ibbeta Ser122/IX had the ability to bind soluble vWF
      and to aggregate in the presence of ristocetin. These results suggest that
      despite disruption of the disulfide linkage between GPIbalpha and GPIbbeta,
      GPIb/IX is formed, but its stability may be impaired, resulting in low levels of
      the complex on the platelet membranes.

PMID- 16978237
TI  - Differential levels of soluble angiopoietin-2 and Tie-2 in patients with
      haematological malignancies.
AB  - The system involving angiopoietin-2 (Ang-2) and its receptor, Tie-2, appears to
      play an important role not only in tumor angiogenesis, but also in the biology of
      haematological and non-haematological malignancies. In the present study we
      evaluated the serum levels of soluble Ang-2 (sAng-2) and soluble Tie-2 (sTie-2)
      in patients with haematological malignancies. Measurements were carried out in 15
      patients with chronic myeloid leukaemia (CML), 25 with essential thrombocythemia
      (ET), 24 with multiple myeloma (MM) and six with monoclonal gammopathy of
      undetermined significance (MGUS). In addition, we correlated the levels of
      angiopoietins with known prognostic factors. sAng-2 and sTie-2 were quantified
      with enzyme-linked immunosorbent assay (ELISA). In patients with CML and MM the
      levels of sAng-2 were significantly higher (1686.53 +/- 936.41 pg/mL and 1917.82
      +/- 1427 pg/mL, respectively) than in controls (n = 15; 996.096 +/- 414.65 pg/mL)
      (P < 0.01). In patients with MM sAng-2 levels were significantly increased with
      increasing stage of disease, from stage I to stage III (P < 0.03) and presented a
      trend of correlation with Beta2-microglobulin levels (r = 0.317) and grade of
      bone involvement. Furthermore, the levels of sAng-2 determined after 6 months of
      chemotherapy in CML patients were significantly lower than at diagnosis in the
      patients who achieved haematological remission. Circulating sTie-2 levels were
      increased in patients with ET (17.5 +/- 9.2 vs 9 +/- 3.5 ng/mL; P < 0.01) and in
      those with CML (16.29 +/- 8.7 ng/mL; P < 0.04). In conclusion, abnormal levels of
      sAng-2 and sTie-2 are present in some haematological malignancies. These markers
      may play a role in the pathophysiology of these conditions and their progression.

PMID- 16978238
TI  - Long-term results of thalidomide in refractory and relapsed multiple myeloma with
      emphasis on response duration.
AB  - OBJECTIVE: Thalidomide administered as a single agent produces a response rate of
      about 40% in patients with refractory or relapsed multiple myeloma (MM). The aim
      of our study was to determine the quality and duration of such responses.
      PATIENTS AND METHODS: Forty-two consecutive patients with refractory (20) or
      relapsed (22) MM were given thalidomide as a single agent at our institution.
      Most of them (70%) had previously received two or more lines of therapy, and 38%
      had undergone autologous stem cell transplantation. RESULTS: Eighteen patients
      (43%) responded to thalidomide [11 minimal responses (MR) and seven partial
      responses (PR)] according to the European Marrow Transplant Registry (EBMT)
      criteria. The median time to response was 3 months and the median duration of
      therapy in responding patients was 9 months. Treatment was discontinued because
      of toxicity in 10 responding patients. The toxicity mainly led to peripheral
      neuropathy and fatigue. At the time of this analysis, all responding patients had
      progressed except one who remains in continued stable PR. The median time to
      progression was 15.6 months (range 1.3 to 70+), with a trend towards a longer
      duration for patients who achieved PR vs. MR (21.2 vs. 11.2 months, P = 0.11).
      The median duration of response was 12.4 months (range: 0.3-67+) (17.2 months for
      PR vs. 9.7 months for MR, P = 0.11). CONCLUSION: These results show that the
      effect of thalidomide in refractory/relapsed MM can be sustained, particularly in
      patients who achieve a greater degree of response, and support the finding that
      this drug can be used for maintenance therapy.

PMID- 16978239
TI  - Initial and late prognostic factors to predict survival in adult acute
      lymphoblastic leukaemia.
AB  - Factors able to predict overall survival in adult patients with acute
      lymphoblastic leukaemia were assessed according to the period since initiation of
      the treatment using a Cox proportional hazards model. This period covers
      successively an initial period during the induction treatment and a consolidation
      period during the postinduction treatment. From 1994 to 2002, 922 patients with
      acute lymphoblastic leukaemia (excluding French-American-British L3 subtype) were
      enrolled in a multicentre protocol and followed, with a mean follow up of 58
      months. A multivariate time-segmented analysis was performed on 658 patients.
      Analyses of the initial (before 100 d) and the late phases were realised after
      stratification on the type of induction treatment and on the different treatment
      strategies respectively. Age was the sole factor that influenced survival during
      the initial phase (hazard ratio 1.48 per 10-yr increase; P < 0.01). Factors that
      predicted survival during the late phase were age (hazard ratio 1.12, P = 0.02),
      white blood cells count (hazard ratio 1.01 per 10(10) cells/L increase; P <
      0.05), lactic dehydrogenase level (hazard ratio 1.001 for 10 IU/L increase; P <
      0.01) and t(9;22) karyotype or miscellaneous others vs. normal karyotype (hazard
      ratios 1.40; P < 0.01 and 1.06; P = 0.04 respectively). This analysis suggests
      that predictive factors may be split into tolerance factors and haematological
      factors. Determination of such factors is crucial to adapt postremission
      therapeutic strategies in acute lymphoblastic leukaemia.

PMID- 16978241
TI  - Methanogenic communities in permafrost-affected soils of the Laptev Sea coast,
      Siberian Arctic, characterized by 16S rRNA gene fingerprints.
AB  - Permafrost environments in the Arctic are characterized by extreme environmental
      conditions that demand a specific resistance from microorganisms to enable them
      to survive. In order to understand the carbon dynamics in the climate-sensitive
      Arctic permafrost environments, the activity and diversity of methanogenic
      communities were studied in three different permafrost soils of the Siberian
      Laptev Sea coast. The effect of temperature and the availability of methanogenic
      substrates on CH4 production was analysed. In addition, the diversity of
      methanogens was analysed by PCR with specific methanogenic primers and by
      denaturing gradient gel electrophoresis (DGGE) followed by sequencing of DGGE
      bands reamplified from the gel. Our results demonstrated methanogenesis with a
      distinct vertical profile in each investigated permafrost soil. The soils on
      Samoylov Island showed at least two optima of CH4 production activity, which
      indicated a shift in the methanogenic community from mesophilic to
      psychrotolerant methanogens with increasing soil depth. Furthermore, it was shown
      that CH4 production in permafrost soils is substrate-limited, although these
      soils are characterized by the accumulation of organic matter. Sequence analyses
      revealed a distinct diversity of methanogenic archaea affiliated to
      Methanomicrobiaceae, Methanosarcinaceae and Methanosaetaceae. However, a
      relationship between the activity and diversity of methanogens in permafrost
      soils could not be shown.

PMID- 16978240
TI  - Venlafaxine-induced ecchymoses and impaired platelet aggregation.
AB  - OBJECTIVE: To describe a case of venlafaxine-induced ecchymoses. METHODS: A
      patient with a history of ecchymoses coincident with venlafaxine therapy was
      rechallenged with the drug. Her platelet function was assessed with aggregation
      and ATP release studies before the rechallenge and after she developed
      ecchymoses. In addition, the effect of venlafaxine on platelet aggregation and
      ATP release was studied in vitro by adding the drug to platelet-rich plasma from
      normal donors. RESULTS: After 4 wk of treatment with venlafaxine our patient
      developed extensive ecchymoses. At that time her platelet aggregation and release
      responses to epinephrine, ADP, collagen, and arachidonic acid were markedly
      suppressed. Adding venlafaxine to normal platelet-rich plasma also dramatically
      reduced the aggregation and release responses to the same agonists as well as to
      serotonin, but the concentrations of venlafaxine required were 1000-fold greater
      than those normally achieved clinically. CONCLUSIONS: Our patient demonstrated an
      idiosyncratic hypersensitivity to the platelet inhibitory effects of venlafaxine.
      Because venlafaxine is an inhibitor of serotonin uptake by platelets and neurons,
      this mechanism may contribute to the impact of this drug on platelet function.
      However, our in vitro studies suggest that this hypothesis is inadequate to
      explain the observations completely.

PMID- 16978242
TI  - Genomic diversity of cultivable Lactobacillus populations residing in the
      neonatal and adult gastrointestinal tract.
AB  - The objective of this study was to investigate the cultivable Lactobacillus
      population in adult and infant faecal material to identify strains shared across
      a number of individuals. A range of lactobacilli isolated on Lactobacillus
      selective agar from faeces of 16 infants and 11 adults were genetically
      fingerprinted and further characterized by 16S rRNA gene sequencing. The
      relatedness of all the Lactobacillus strains isolated to known species was also
      determined both genetically and phenotypically. This study revealed that the
      human intestine is initially colonized by only a few (1-2) different cultivable
      strains whereas in adults the pattern becomes more complex with a higher
      diversity of strains. The adult samples contained three genetically distinct
      Lactobacillus strains in some cases, while infant samples generally harboured
      only one dominant Lactobacillus strain. Moreover, the species in general appeared
      to differ with Lactobacillus rhamnosus and Lactobacillus casei/paracasei found
      mainly in adults, whereas Lactobacillus gasseri and Lactobacillus salivarius were
      more commonly isolated in infant samples. The data reaffirm the differences in
      Lactobacillus populations both between individual subjects and between the infant
      and adult, with an overall change in the diversity and complexity from early
      stages of life to adulthood.

PMID- 16978243
TI  - Size and structure of bacterial, fungal and nematode communities along an
      Antarctic environmental gradient.
AB  - The unusually harsh environmental conditions of terrestrial Antarctic habitats
      result in ecosystems with simplified trophic structures, where microbial
      processes are especially dominant as drivers of soil-borne nutrient cycling. We
      examined soil-borne Antarctic communities (bacteria, fungi and nematodes) at five
      locations along a southern latitudinal gradient from the Falkland Islands (51
      degrees S) to the base of the Antarctic Peninsula (72 degrees S), and compared
      principally vegetated vs. fell-field locations at three of these sites. Results
      of molecular (denaturing gradient gel electrophoresis, real-time PCR),
      biochemical (ergosterol, phospholipid fatty acids) and traditional
      microbiological (temperature- and medium-related CFU) analyses were related to
      key soil and environmental properties. Microbial abundance generally showed a
      significant positive relationship with vegetation and vegetation-associated soil
      factors (e.g. water content, organic C, total N). Microbial community structure
      was mainly related to latitude or location and latitude-dependent factors (e.g.
      mean temperature, NO3, pH). Furthermore, strong interactions between vegetation
      cover and location were observed, with the effects of vegetation cover being most
      pronounced in more extreme sites. These results provide insight into the main
      drivers of microbial community size and structure across a range of terrestrial
      Antarctic and sub-Antarctic habitats, potentially serving as a useful baseline to
      study the impact of predicted global warming on these unique and pristine
      ecosystems.

PMID- 16978244
TI  - Saliva can mediate HIV-1-specific antibody-dependent cell-mediated cytotoxicity.
AB  - HIV is not usually transmitted by saliva from HIV-1-infected individuals.
      Antiviral substances in saliva responsible for this may include HIV-1-specific
      antibody-dependent cell-mediated cytotoxicity (ADCC). We evaluated saliva ADCC
      titers of 62 HIV-1-infected women from the Women's Interagency HIV Study (WIHS)
      and 55 uninfected individuals. HIV-1-infected women were less likely to have ADCC
      activity in saliva than in serum or cervical lavage fluid (CVL). 24% of HIV-1
      positive women and a similar percentage of uninfected women had HIV-1-specific
      saliva ADCC activity. A significant amount of saliva ADCC activity in infected
      women was HIV-gp120-specific. These studies demonstrate that HIV-specific ADCC
      activity can be present in saliva. This activity may contribute to host defence
      against initial infection with HIV.

PMID- 16978245
TI  - Right ventricular apical pacing: all right?

PMID- 16978246
TI  - A single pulmonary vein as electrophysiological substrate of paroxysmal atrial
      fibrillation.
AB  - INTRODUCTION: It has been demonstrated that pulmonary veins (PVs) play an
      important role in initiation and maintenance of paroxysmal atrial fibrillation
      (AF). However, it is not clearly known whether a single PV acts as
      electrophysiological substrate for paroxysmal AF. METHODS AND RESULTS: This study
      included five patients with paroxysmal AF. All patients underwent complete PV
      isolation with continuous circular lesions (CCLs) around the ipsilateral PVs
      guided by a three-dimensional mapping system. Irrigated radiofrequency (RF)
      delivery was performed during AF on the right-sided CCLs in two patients and on
      the left-sided CCLs in three patients. The incomplete CCLs resulted in a change
      from AF to atrial tachycardia (AT), which presented with an identical atrial
      activation sequence and P wave morphology. Complete CCLs resulted in AF
      termination with persistent PV tachyarrhythmias within the isolated PV in all
      five patients. PV tachyarrhythmia within the isolated PV was PV fibrillation from
      the left common PV (LCPV) in two patients, PV tachycardia from the right superior
      PV (RSPV) in two patients, and from the left superior PV in one patient. All
      sustained PV tachyarrhythmias persisted for more than 30 minutes, needed external
      cardioversion for termination in four patients and a focal ablation in one
      patient. After the initial procedure, an AT from the RSPV occurred in a patient
      with PV fibrillation within the LCPV, and was successfully ablated. CONCLUSION:
      In patients with paroxysmal AF, sustained PV tachyarrhythmias from a single PV
      can perpetuate AF. Complete isolation of all PV may provide good clinical outcome
      during long-term follow-up.

PMID- 16978247
TI  - "Left-variant" atypical atrioventricular nodal reentrant tachycardia:
      electrophysiological characteristics and effect of slow pathway ablation within
      coronary sinus.
AB  - INTRODUCTION: Recent anatomical and electrophysiological studies have
      demonstrated the presence of leftward posterior nodal extension (LPNE); however,
      its role in the genesis of atrioventricular nodal reentrant tachycardia (AVNRT)
      is poorly understood. This study was performed to characterize successful slow
      pathway (SP) ablation site and to elucidate the role of LPNE in genesis of
      atypical AVNRT with eccentric activation patterns within the coronary sinus (CS).
      METHODS AND RESULTS: Among 45 patients with atypical AVNRT (slow-slow/fast
      slow/both = 20/22/3 patients) with concentric (n = 37, 82%) or eccentric CS
      activation (n = 8, 18%), successful ablation site was evaluated. Among 35/37
      patients (95%) with concentric CS activation, ablation at the conventional SP
      region outside CS eliminated both retrograde SP conduction and AVNRT
      inducibility. Among eight patients with eccentric CS activation, the earliest
      retrograde atrial activation was found at proximal CS 16 +/- 4 mm distal to the
      ostium during AVNRT. The earliest retrograde activation site was located at
      inferior to inferoseptal mitral annulus, consistent with the presumed location of
      LPNE. Ablation at the conventional SP region with electroanatomical approach only
      rendered AVNRT nonsustained without elimination of retrograde SP conduction in
      seven of eight patients (88%). Ablation targeted to the earliest retrograde
      atrial activation site within proximal CS (15 +/- 4 mm distal to the ostium);
      however, eliminated retrograde SP conduction and rendered AVNRT noninducible in
      six of eight patients (75%). CONCLUSION: In 75% of "left-variant" atypical AVNRT,
      ablation within proximal CS was required to eliminate eccentric retrograde SP
      conduction and render AVNRT noninducible, suggesting LPNE formed retrograde limb
      of reentrant circuit.

PMID- 16978248
TI  - Paradoxical atrial undersensing: noise rate reversion or amplifier ringing?
AB  - Atrial tachy-arrhythmias may give rise to mode switching or noise rate reversion
      in dual-chamber pacemakers. In case of high amplitude of the atrial electrogram
      during tachycardia, a paradoxical behavior of atrial sensitivity programming can
      be observed. Two patients with implanted dual-chamber pacemakers showed
      intermittent and complete loss of atrial sensing during atrial tachycardia during
      device programming to a higher atrial sensitivity setting. This phenomenon is
      caused by amplifier ringing and can be considered as a state of amplifier
      saturation, which disables atrial sensing in spite of the high amplitude of the
      atrial signal. In patients with high amplitude of the atrial electrogram during
      atrial tachycardia, a paradoxical behavior of sensitivity programming resulting
      in atrial undersensing can be observed.

PMID- 16978249
TI  - Should "artificial" high altitude environments be considered doping?

PMID- 16978250
TI  - Heart rate variability during high-intensity field exercise in female distance
      runners.
AB  - The purposes of this study were to demonstrate the transition of heart rate
      variability (HRV) during trials in the field and to examine the relationship
      between peak frequency of high-frequency band (HF) and stride frequency. Ten
      healthy long-distance college female runners (age 19-21 years) performed a 3000 m
      realistic time trial. The time-series power spectrum analysis by maximum entropy
      method was used to evaluate cardiac autonomic nervous activity during the race.
      Cross-correlation coefficients were calculated to estimate the degree of linear
      co-ordination between the central peak frequency of HF and stride frequency. Just
      after starting, the decrease in HF (0.15-1.00 Hz) and a transient increase of low
      frequency band (LF)/HF were found. After that, the HF remained at a low level and
      LF/HF decreased sharply. These findings suggested that the parasympathetic
      activity was suppressed and sympathetic activity increased just after starting,
      and the sympathetic activity reached the saturated level according to
      continuation of high-intensity exercise. In spite of the significant decrease of
      HRV during trials, peak frequency of HF could be differentiated clearly. The
      cross-correlation coefficient of peak frequency of HF and stride frequency was
      from 0.703 to 0.868. This finding indicated that exercise rhythm reflected HRV
      during high-intensity running in the field.

PMID- 16978251
TI  - Assessment of the effect of endurance training on left ventricular relaxation
      with magnetic resonance imaging.
AB  - The purpose of the study was to assess the effect of endurance training on the
      early diastolic global and regional left ventricular (LV) relaxation with three
      magnetic resonance imaging (MRI) techniques. Fourteen subjects were examined with
      MRI before and after 3-month endurance training. Global early diastolic LV
      myocardial relaxation was assessed with mitral flow velocity mapping and regional
      LV early myocardial relaxation with myocardial tagging. LV end-diastolic and end
      systolic volumes and mass were assessed with cine Magnetic resonance imaging
      (MRI). Mitral flow velocity mapping analysis revealed that the time to peak early
      filling shortened after training (before 112+/-32 ms, after 97+/-21, P<0.05),
      indicating more rapid global early myocardial relaxation. LV mass increased (97+/
      19 g, 105+/-18, P<0.01) and end-systolic volume decreased (47+/-11 mL, 42+/-13,
      P<0.05). According to myocardial tagging analysis early myocardial relaxation in
      the septum and in the LV lateral wall increased (P<0.05). Regional tagging
      analysis showed enhanced myocardial relaxation in the basal septum (P<0.05).
      Global and regional LV early diastolic relaxation improved and physiological LV
      hypertrophy was found after the exercise training period for 3 months in healthy
      sedentary subjects.

PMID- 16978252
TI  - Knee injuries account for the sports-related increased risk of knee
      osteoarthritis.
AB  - Increased risk of osteoarthritis has been found among athletes active in
      different kinds of sports. Knee injury is an established risk factor for knee
      osteoarthritis. In this population-based case-control study we investigated the
      risk of knee osteoarthritis with respect to sports activity and previous knee
      injuries. A total of 825 cases with x-ray-verified femorotibial osteoarthritis
      were identified at six hospitals in southern Sweden. The cases were matched (age,
      sex and residential area) with 825 controls from the general population. Mailed
      questionnaire data on sports activity for more than 1 year after the age of 16,
      knee injuries and confounding variables (weight, height, heredity, smoking and
      occupation) were collected and analyzed using logistic regression models. The
      response frequency was 89%. Among men knee osteoarthritis was related to soccer
      (odds ratio (OR) 1.6, 95% confidence interval (CI) 1.1-2.2), ice hockey (OR 1.9,
      95% CI 1.2-3.0) and tennis (OR 2.0, 95% CI 1.1-3.8) but not to track and field
      sports, cross-country skiing, and orienteering. After adjustment for confounding
      variables soccer and ice hockey remained significantly related to knee
      osteoarthritis, but after adjustment for knee injuries no significant relation
      remained. The sports-related increased risk for knee osteoarthritis was explained
      by knee injuries.

PMID- 16978253
TI  - Effects of an intermittent exercise fatigue protocol on biomechanics of soccer
      kick performance.
AB  - The purpose of this study was to examine the effects of fatigue on biomechanical
      indices of soccer kick performance. Ten male amateur soccer players performed
      maximal instep kicks prior to, in the middle and after the implementation of a 90
      min intermittent exercise protocol. Three-dimensional data, ground reaction
      forces (GRFs) and segmental moments were measured during the kick while blood
      lactate and ammonia concentrations were monitored throughout the protocol.
      Analysis of variance designs with repeated measures indicated a significant
      increase in ammonia (P<0.01) and lactate levels (P<0.01) following fatigue. The
      GRFs and joint displacement curves during the kick remained unaltered after
      fatigue (P>0.01). However, post-fatigue maximum angular velocity of the shank,
      the net moments acting on the shank and the resultant joint moments were
      significantly lower compared with the corresponding pre-exercise values (P<0.01).
      The velocity of the ball was 24.69 m/s prior to the protocol and significantly
      decreased to 21.78 m/s after (P<0.01). Similarly, the ball/foot speed ratio
      significantly (P<0.01) declined from 1.40+/-0.12 (pre-fatigue) to 1.33+/-0.18
      (post-fatigue). The present results suggest that an exercise protocol that
      simulates soccer game conditions results in significant impairment of soccer kick
      performance. This could be attributed to alterations of the function of the
      neuromuscular system and force generation capacity, which may have altered the
      mechanics of soccer kick performance.

PMID- 16978254
TI  - Effect of expertise and visual contribution on postural control in soccer.
AB  - This work analyzes the postural performance and the use of visual information in
      soccer players according to their level of competition. Two groups of healthy
      soccer players were investigated at the mid-competition season: an amateur (AM)
      (n=15) group composed of regional-level players and a professional group at a
      national level (PRO) (n=15). Posture was assessed by measuring the center of foot
      pressure (COP) with a force platform during a test (51.2 s) of bipedal quiet
      standing posture. The test was completed with eyes open (the subjects looked at a
      fixed-level target at a distance of 2 m) and closed (they kept their gaze in a
      straight-ahead direction). The statistical analysis showed that PRO soccer
      players were more stable than AM soccer players. Moreover, the contribution of
      vision in postural maintenance was less important in the PRO players than in the
      AM players. The present study suggests that intense training allows PRO soccer
      players to become less dependent on vision to control their posture such that
      vision can be dedicated to treating the information, that emanates from the game.

PMID- 16978255
TI  - High-intensity resistance and cardiovascular training improve physical capacity
      in cancer patients undergoing chemotherapy.
AB  - The purpose of the study was to examine the effects of a supervised high- and low
      intensity structured training program in cancer patients concurrently undergoing
      chemotherapy. Seventy patients, in different stages of the disease and with
      different diagnoses (48 females, 22 males), between 18 and 65 years of age (mean
      age 42.8) participated in a 9-h weekly training program over 6 weeks. The
      intervention involved physical exercise, relaxation, massage, and body-awareness
      training. Physical capacity (one-repetition maximum tests (1RM), VO2max) and body
      composition (weight, skin-fold) were compared before and after the exercise
      intervention. The average increase in muscular strength was 41.3% (P<0.001) and
      14.5% in aerobic fitness (pre: 2.27+/-0.597 L/min, post: 2.56+/-0.644 L/min,
      (P<0.001). The exercise intervention significantly increased the weight of the
      subjects by 1% (pre: 72.62+/-13.42 kg, post: 73.25+/-13.44 kg, P=0.016). There
      was a significant decrease in skin-fold measurements by 3% (P=0.031). The
      exercise intervention was well tolerated, provided that daily screening criteria
      were adhered to. The effects of resistance and cardiovascular training observed
      in this short-term study support the theory that exercise is a beneficial
      intervention strategy for increasing muscle strength and aerobic fitness during
      antineoplastic chemotherapy. This type of exercise program can be an important
      component of complementary treatment for cancer patients undergoing chemotherapy.

PMID- 16978257
TI  - "Voices of the broken body." The resumption of non-professional female players'
      sports careers after anterior cruciate ligament injury. The female player's
      dilemma: is she willing to run the risk?
AB  - The article takes as its starting point the lived experiences of female sports
      patients in rehabilitation. The research data are semi-structured qualitative
      interviews (N=17) with non-professional female players as patients, having
      anterior cruciate ligament injuries (ACL-injuries). Injury narratives have been
      conducted, with a focus upon how female handball players managed the injured
      situation. Ethnographic research was taken in a private physiotherapy clinic over
      a period of more than 1 (1/2) years. The narratives show the impact of risk
      management - the individual coping strategy of the players. The handball her
      player has choices to make regarding the resumption of the career. The options
      and possibilities of playing or not playing after an ACL-injury are connected to
      the trust in the capacity of the body. The concept of bodily risk reflexive
      coping strategy is constructed to understand the question of the resumption of
      the career. The individualistic self-care management indicates a manageable body
      with a desire to act as worthy of being a full part of the sporting society. This
      strategy is adding to the sense of accomplishment and to the continuing
      development of self-identity. The study shows that there is a need for guidance
      in the injury process. Playing is connected with pleasurable feelings and
      excitements, but the her-player does care for the bodily self and her risk
      assessment is so far not a "misuse" or a consumption of sports medicine in the
      name of sporting achievements.

PMID- 16978256
TI  - An examination of the factorial structure of the Norwegian version of the sport
      anxiety scale.
AB  - The purpose of the present research was to develop and validate a Norwegian
      version of the sport anxiety scale (SAS-N), a multidimensional sport performance
      trait anxiety inventory. The SAS consists of three unique dimensions measuring
      somatic anxiety, worry and concentration disruption, respectively. The
      translation-back translation method was used in development of the SAS-N, and
      athletes from different sports in Norway (N=282) participated in the study. The
      findings are similar to those of the English original, and lend support for the
      use of this instrument with Norwegian athlete subjects.

PMID- 16978258
TI  - Identification of the first Oomycete annexin as a (1-->3)-beta-D-glucan synthase
      activator.
AB  - (1-->3)-beta-D-Glucans are major components of the cell walls of Oomycetes and as
      such they play an essential role in the morphogenesis and growth of these
      microorganisms. Despite the biological importance of (1-->3)-beta-D-glucans,
      their mechanisms of biosynthesis are poorly understood. Previous studies on (1-
      >3)-beta-D-glucan synthases from Saprolegnia monoica have shown that three
      protein bands of an apparent molecular weight of 34, 48 and 50 kDa co-purify with
      enzyme activity. However, none of the corresponding proteins have been
      identified. Here we have identified, purified, sequenced and characterized a
      protein from the 34 kDa band and clearly shown that it has all the biochemical
      properties of proteins from the annexin family. In addition, we have
      unequivocally demonstrated that the purified protein is an activator of (1-->3)
      beta-D-glucan synthase. This represents a new type of function for proteins
      belonging to the annexin family. Two other proteins from the 48 and 50 kDa bands
      were identified as ATP synthase subunits, which most likely arise from
      contaminations by mitochondria during membrane preparation. The results, which
      are discussed in relation with the possible regulation mechanisms of (1-->3)-beta
      D-glucan synthases, represent a first step towards a better understanding of cell
      wall polysaccharide biosynthesis in Oomycetes.

PMID- 16978259
TI  - Identification of Bacillus cereus internalin and other candidate virulence genes
      specifically induced during oral infection in insects.
AB  - Bacillus cereus is an opportunistic bacterium frequently associated with food
      borne infections causing gastroenteritis. We developed an in vivo expression
      technology (IVET), with an insect host, for identification of the B. cereus genes
      specifically expressed during infection. This IVET-based approach uses site
      specific recombinase TnpI to identify transient promoter activation. We
      constructed a genomic library of B. cereus ATCC14579 by cloning DNA fragments
      upstream from tnpI. The library was screened in vivo by oral infection of the
      insect Galleria mellonella. We selected 100 clones from dead larvae. Sequencing
      of the inserts followed by a second screen for specific in vivo induction led to
      the identification of 20 in vivo-induced genes (ivi genes). They belonged to
      several different functional classes: regulation, metabolism, DNA repair and
      replication, cell division, transport, virulence and adaptation. A strongly
      induced gene, ivi29, was further analysed. It encodes an internalin-like protein
      with four distinct domains: an N-terminal signal peptide for export, a NEAT
      domain thought to be involved in iron transport, a leucine-rich repeat domain
      that may interact with host cells, and a C-terminal SLH domain presumably binding
      the protein to the peptidoglycan. As suggested by a Fur box in the promoter,
      transcriptional analysis showed ivi29 expression to be repressed by iron,
      suggesting that expression was induced in vivo due to iron deprivation in the
      host. This iron-regulated, leucine-rich surface protein was designated IlsA.
      Disruption of ilsA reduced the virulence of the bacteria to the insect larvae
      indicating its role in the overall pathogenesis of B. cereus.

PMID- 16978260
TI  - Pili with strong attachments: Gram-positive bacteria do it differently.
AB  - Bacteria attach to their appropriate environmental niche by using adhesins. To
      maximize their contact with the environment, adhesins are often present on the
      ends of long hairlike structures called pili. Recently, attention has focused on
      pili of Gram-positive bacteria because they may be vaccine candidates in
      important human pathogens. These pili differ from the well-studied pili of Gram
      negative bacteria because their subunits are covalently linked, they do not
      require specific chaperones for assembly, and the tip protein (likely to be the
      adhesin) is not required to initiate formation of the pilus structure. In Gram
      positive bacteria, the genes for pili occur in clusters, which may constitute
      mobile genetic elements. These clusters include the transpeptidase(s) of the
      sortase family that is/are required for polymerization of the subunit proteins.
      However, efficient covalent attachment of the completed pilus structure to the
      cell wall is accomplished, in cases where this has been studied, by the
      'housekeeping' sortase, which is responsible for attachment to the peptidoglycan
      of most surface proteins containing cell wall sorting signals. This enzyme is
      encoded elsewhere on the genome. Because pili of Gram-positive bacteria have not
      been extensively investigated yet, we hope that this MicroReview will help to
      pinpoint the areas most in need of further study.

PMID- 16978262
TI  - The future role of intelligent probes in detecting and managing prostate cancer.

PMID- 16978263
TI  - THE Wnt signalling pathway is a potential therapeutic target in prostate cancer.

PMID- 16978264
TI  - Does robotically assisted radical prostatectomy result in better preservation of
      erectile function?

PMID- 16978265
TI  - Inadequacies in funding for the cost of nephrectomies in a tertiary referral
      centre in the UK.

PMID- 16978266
TI  - Improving outcomes in early prostate cancer: Part I--adjuvant treatment.

PMID- 16978267
TI  - Improving outcomes in early prostate cancer: Part II--neoadjuvant treatment.

PMID- 16978268
TI  - Low penetrance genetic susceptibility to kidney cancer.

PMID- 16978269
TI  - The management of neurogenic bladder and quality of life in spinal cord injury.

PMID- 16978270
TI  - The changing distribution of pT stage in testicular germ cell tumours from 1976
      to 2005: a single-centre analysis of histopathological reports.
AB  - OBJECTIVE: To assess the changing distribution of stage in seminoma and
      nonseminomatous germ cell tumours (NSGCTs), as recent reports contained no
      detailed information on pT stage and vascular invasion, important factors in the
      decision for further treatment. PATIENTS AND METHODS: Histopathological reports
      from 1976 to 2005, from patients who had surgery for testicular tumours at the
      authors' institution, were investigated with special focus on pT stage and its
      distribution. The whole study period was divided into six 5-year periods. The
      incidence of seminoma was compared with NSGCT, defined according to the Tumour
      Nodes-Metastasis (TNM) classification. RESULTS: In each 5-year period the median
      number of tumours treated surgically was 86; the distribution of seminomas and
      NSGCTs remained stable during the study period (P = 0.201). pT4 and pT3 tumours
      declined or disappeared in both histopathological groups, while pT2 and pT1
      tumours increased during the study period. Since 1996-2000, pT1 tumours
      decreased, whereas pT2 tumours increased in seminomas (P = 0.085) and NSGCTs (P =
      0.003). CONCLUSION: The incidence of seminoma and NSGCT has not changed over the
      last 30 years in Vienna. With the establishment of vascular invasion in the TNM
      classification in 1997, the incidence of pT1 decreased while that of pT2
      increased. Since then, the incidence of pT1 tumours in seminomas was 45.8% and
      29.1% in NSGCT. According to generally accepted treatment guidelines, these
      patients might need no adjuvant treatment after surgery.

PMID- 16978271
TI  - Two different perspectives in the management of pT3 and/or margin-positive
      prostate cancer after radical prostatectomy.

PMID- 16978272
TI  - Measuring the psychosocial impact of population-based prostate-specific antigen
      testing for prostate cancer in the UK.
AB  - OBJECTIVE: To evaluate the psychosocial impact of participation in a population
      based prostate-specific antigen (PSA) testing programme, akin to screening, and
      to explore the relationship between urinary symptoms reported before PSA testing
      and the response to the subsequent PSA result. PATIENTS AND METHODS: This
      prospective questionnaire study was nested within the case-finding component of
      the ProtecT (prostate testing for cancer and treatment) feasibility study
      (ISRCTN20141297). Men aged 50-69 years from 18 general practices in three cities
      in the UK completed the Hospital Anxiety and Depression Scale (HADS), the Short
      Form-12 (SF-12) Health Survey, and the International Continence Society 'male'
      (ICSmale) questionnaires before giving consent for a PSA test in a community
      clinic (baseline). Men with an 'abnormal' PSA result returned for further
      investigation (including biopsy) and repeated these questionnaires before biopsy.
      RESULTS: At baseline, study participants had similar levels of anxiety and
      depression to the general male population. There was no increase in the HADS
      scores, or reduction in the SF-12 mental health component summary score, on
      attendance at the biopsy clinic after receiving an 'abnormal' PSA result. Urinary
      symptoms were associated with levels of anxiety and depression before receiving a
      PSA result (baseline), but were not associated with anxiety and depression at
      biopsy independently of baseline scores. Therefore changes in anxiety or
      depression at biopsy did not appear to differ between those with and without
      urinary symptoms. CONCLUSIONS: This study confirms the findings of other studies
      that the deleterious effects of receiving an abnormal PSA result during
      population screening are not identified by generic health-status questionnaires.
      Comparisons with outcomes of studies measuring cancer-specific distress and using
      qualitative research methods raise the question of whether a prostate cancer
      screening-specific instrument is required. However, a standardized measure of
      anxiety identified differences at baseline between those who did and did not
      report urinary symptoms. These findings suggest that it might be advisable to
      better inform men undergoing PSA testing about the uncertain relationship between
      urinary symptoms and prostate cancer, to minimize baseline levels of
      psychological distress.

PMID- 16978273
TI  - African-American race is a predictor of prostate cancer detection: incorporation
      into a pre-biopsy nomogram.
AB  - OBJECTIVES: To construct a pre-biopsy predictive model incorporating several
      clinical variables, including African-American (AA) or Caucasian race, to predict
      the risk of prostate cancer detection on prostate biopsy, as traditionally AA men
      have had a higher incidence of prostate cancer than Caucasian men, but previous
      predictive tools for prostate cancer have not incorporated the effect of race.
      PATIENTS AND METHODS: We evaluated 9473 patients undergoing initial prostate
      biopsy at three equal-access healthcare institutes from 1993 to 2003. At each
      biopsy session, patient age, race, serum prostate-specific antigen level (PSA),
      digital rectal examination (DRE) findings, number of biopsy cores taken, year of
      biopsy, and pathological findings were recorded. A logistic regression model was
      constructed to evaluate predictors of cancer detection based on pre-biopsy
      variables. The model was internally validated using the bootstrap statistical
      method, and a nomogram was constructed. RESULTS: Prostate cancer was diagnosed in
      1895 (33%) AA men and 991 (26%) Caucasians. AA men had a significantly higher
      mean serum PSA level than Caucasians, at 13.0 and 8.5 ng/mL, respectively (P <
      0.001). The mean ages were similar between AA and Caucasian men (P = 0.23), but
      Caucasian men had a higher incidence of an abnormal DRE (P < 0.001). On
      multivariate analysis, age, race, year of biopsy, PSA level, DRE, and number of
      cores taken were all statistically significant (P < 0.001). Hazard ratios were
      (controlling for year of biopsy); age (1.30), Caucasian race (0.74), PSA level
      (1.47), DRE (1.75), and number of cores taken (1.19). The predicted model had a
      boot-strapped concordance index of 0.75. CONCLUSION: AA race remains an
      independent predictor of prostate cancer detection in men undergoing initial
      prostate biopsy. This nomogram is the first to individualise the risk by AA or
      Caucasian race in a predictive model for counselling men on their probability of
      having cancer at the time of their first biopsy.

PMID- 16978274
TI  - Mass screening for prostate cancer in patients with end-stage renal disease: a
      comparative study.
AB  - OBJECTIVE: To determine the usefulness of prostate-specific antigen (PSA)
      screening for prostate cancer in patients with end-stage renal disease (ESRD), as
      although serum PSA is effective in the early detection of this cancer in the
      general population, there are few reports of its utility in patients with ESRD.
      PATIENTS AND METHODS: Blood samples were obtained for PSA screening from April
      2002 to September 2003; 1250 men with ESRD aged >50 years were compared with 1007
      healthy control men aged >55 years, all in Kumamoto Prefecture, Japan. All men
      with a serum PSA level of >4.0 ng/mL were categorized as PSA-positive and were
      further assessed, including a prostate biopsy. RESULTS: There was a statistically
      significantly greater increase in PSA level with age in the ESRD group than in
      the healthy controls. The rate of cancer detection among men with a PSA level of
      >10 ng/mL was significantly higher in patients with ESRD than in healthy
      controls. Thirteen patients with ESRD and five healthy control men were finally
      diagnosed with prostate cancer. CONCLUSION: The serum PSA level was slightly
      higher and the incidence of prostate cancer at higher PSA levels appeared to be
      greater in men with ESRD than in healthy controls. The findings of this large
      study suggest that PSA screening is useful for the diagnosis of prostate cancer
      in these patients.

PMID- 16978275
TI  - Impact of surgical treatment on nocturia in men with benign prostatic
      obstruction.
AB  - OBJECTIVES: To validate the International Consultation on Incontinence Nocturia
      Quality-of-life (NQoL) questionnaire in Italian (IT-NQoL) and use it to evaluate
      the impact of surgical treatment on nocturia in men with lower urinary tract
      symptoms related to benign prostatic obstruction (LUTS/BPO). PATIENTS AND
      METHODS: All men attending one urological unit between November 2004 and April
      2005 were enrolled in the study. They were assessed in two groups; those with and
      with no LUTS/BPO. An Italian translation of the NQoL was devised, and patients
      then completed this and validated Italian versions of the International Prostate
      System Score (IPSS), the Pittsburg Sleep Quality Index (PSQI) and the Epworth
      Sleepiness Scale (ESS). Clinical, laboratory and instrumental data from each
      patient were recorded. The patients with LUTS/BPO then had surgical treatment,
      and 6 months later those with LUTS/BPO were asked to complete all the
      questionnaires again to evaluate the test sensitivity to change. RESULTS: Of the
      109 patients enrolled in the study, 61 were affected by LUTS/BPO and 48 were not.
      Cronbach's alpha for the IT-NQoL was 0.943 (95% confidence interval, CI, 0.922
      0.959; P < 0.001) and the intra-class correlation coefficient was 0.999 (95% CI
      0.998-0.999; P < 0.001) for the total IT-NQoL score. The correlation between the
      test and the re-test was statistically significant (P < 0.001; r = 0.999) for all
      items. The mean (sd) IT-NQoL score showed an improvement in QoL from before, at
      23.4 (10.1), to after treatment, at 3.09 (2.48) (P < 0.001). In the LUTS/BPO
      group, the IT-NQoL correlated with the number of times when waking to urinate
      (Pearson's coefficient 0.80, P < 0.001). There was also a correlation for ESS
      (0.796) and for the seven PSQI subscales (0.614, both P < 0.001). The decrease in
      sleep quality, duration and efficiency resulted in an increase in daytime
      sleepiness (r = 0.639, 0.642). At the 6-month follow-up, all questionnaire
      results were statistically different from those before treatment. CONCLUSIONS:
      The IT-NQoL is the first validated translation of the primary instrument into
      another language. This version is easy to use and has the same characteristic
      validity as the English version. Using the IT-NQoL showed that surgical treatment
      determines a decrease in the nocturia rate and an increase in QoL. There was also
      a significant increase in QoL after treatment as assessed by all the other
      questionnaires.

PMID- 16978276
TI  - A prospective observational trial of pelvic floor muscle training for female
      stress urinary incontinence.
AB  - OBJECTIVE: To assess the impact of pelvic floor muscle training (PFMT) on bladder
      neck mobility in a prospective observational study, and to correlate any observed
      changes with objective, standardized outcome measures of the severity of stress
      urinary incontinence (SUI). PATIENTS AND METHODS: Women with the symptom of SUI
      were recruited prospectively over a 3-year period from a tertiary referral
      urogynaecology clinic in a teaching hospital. A group of 97 treatment-naive women
      complaining of SUI and confirmed as having urodynamic SUI on video-urodynamic
      assessment agreed to participate. Bladder neck mobility on perineal
      ultrasonography was assessed immediately before and on completing a 14-week
      programme of 'PFM rehabilitation'. Treatment outcome was assessed using a
      standardized pad-test and a condition-specific, validated quality-of-life
      questionnaire (King's Health Questionnaire). Changes in functional anatomy were
      quantified using transperineal ultrasonography to measure the bladder neck
      position at rest, maximum PFM contraction and maximum Valsalva manoeuvre. Bladder
      neck rotational mobility from rest to maximum incursion and maximum excursion was
      calculated. RESULTS: Treatment with an intensive package of PFMT and behavioural
      modification resulted in significant elevation of the bladder neck position at
      all three measured positions. Displacement of the bladder neck on Valsalva
      (rotational excursion) was reduced after treatment, suggesting increased levator
      'stiffness'. These changes in functional anatomy were associated with a
      statistically and clinically significant reduction in urine loss and improvement
      in condition-specific quality of life. CONCLUSION: The present results show that
      PFMT is an effective treatment for SUI and provide an important new insight into
      how dynamic pelvic floor anatomy can be modified by this widely used
      intervention.

PMID- 16978277
TI  - Chronic prostatitis during puberty.
AB  - OBJECTIVE: To investigate the features of chronic prostatitis (CP) during puberty
      and the effects of biofeedback on young males with this disease. PATIENTS AND
      METHODS: In all, 40 patients were divided into two groups; group 1 included 25
      pubertal patients with CP (mean age 16.5 years, sd 1.1) and group 2 was a control
      group including 15 patients (mean age 16.2 years, sd 1.2) with a normal lower
      urinary tract. National Institute of Health-Chronic Prostatitis Symptom Index
      (NIH-CPSI) scores (three parts) were assessed individually in both groups.
      Expressed prostatic secretions and urine samples after prostate massage from
      group 1 were cultured to determine whether patients were infected with bacteria,
      and group 1 was categorized into various NIH types. Each patients in the two
      groups underwent urodynamics and group 1 were treated with biofeedback. RESULTS:
      In group 1, there were one, three and 21 patients with type II, IIIA and IIIB
      prostatitis. The incidence of staccato voiding and detrusor-sphincter dyssynergia
      (DSD), and the maximum urinary flow rate (Qmax), postvoid residual urine volume
      (PVR), maximum detrusor pressure (Pdetmax) and maximum urethral closure pressure
      (MUCP) between the groups were significantly different (P < 0.05). The total NIH
      CPSI scores and all the subdomains between the groups before biofeedback were
      significantly different (P < 0.001). In group 1 the difference in NIH-CPSI scores
      and Qmax before and after biofeedback was significant (P < 0.05). CONCLUSIONS:
      The main type of CP during puberty is IIIB; the dominating symptom is a voiding
      disorder. The impact on life and psychological effects are substantial. Pubertal
      boys with CP have pelvic floor dysfunction and several abnormal urodynamic
      values, i.e. staccato voiding, DSD, decreasing Qmax, and increasing Pdetmax and
      MUCP. The effect of biofeedback strategies for treating pubertal CP is
      satisfactory.

PMID- 16978278
TI  - Introital ultrasonography: a comparison of women with stress incontinence due to
      urethral hypermobility and continent women.
AB  - OBJECTIVE: To determine if there is a variable on introital ultrasonography (IUS)
      that can be used to distinguish between women with stress urinary incontinence
      (SUI) due to urethral hypermobility (UH) and continent women. PATIENTS AND
      METHODS: This single-centre, prospective, blind, cohort, observational study
      comprised 383 women (245 continent and 138 incontinent) who were all
      appropriately informed volunteers selected according to the inclusion criteria.
      IUS with a convex probe was performed on all women; the measurement plane was
      standardized and coordinates were obtained at rest and on straining. Several
      distances were measured to determine if any provided an objective distinction
      between continent and incontinent women. RESULTS: Among all the IUS variables
      assessed, sliding (calculated as the difference between the distance urethra
      bladder neck, U-BN, at rest and under stress) was the best for distinguishing
      continent and incontinent women. The receiver operating characteristic curves
      showed that with a threshold of 8 mm, sliding had a sensitivity of 92% and a
      specificity of 79.6% for detecting SUI due to UH. The distances symphysis-urethra
      (S-U) and U-BN at rest could also discriminate, but with lower significance.
      CONCLUSIONS: IUS is an important tool for diagnosing SUI; there are three
      independent variables, one dynamic (sliding) and two static (distances S-U and U
      BN), that can be used to distinguish between continent women and those with SUI
      due to UH. Sliding is the most reliable, as it has the highest sensitivity and
      specificity. We think that the simplicity, low financial cost and reliability of
      IUS could allow it to be a routine procedure for physicians working in
      incontinence units.

PMID- 16978279
TI  - Anatomical foundations and surgical manoeuvres for precise identification of the
      prostatovesical junction during robotic radical prostatectomy.
AB  - OBJECTIVE: To develop a technique to identify the bladder neck during robotic
      radical prostatectomy (RRP) using anatomical and patient studies, and to evaluate
      its efficacy during and after surgery. PATIENTS AND METHODS: The data for this
      study were from 10 fresh cadaveric dissections and 50 consecutive athermal RRPs
      performed at our institution. We used a technique we term 'the bimanual bladder
      neck pinch'. RESULTS: The technique helped us to identify the prostatovesical
      junction and to decrease the time required to dissect the bladder neck, and the
      time for urethrovesical anastomosis. Urinary continence requiring 0-1 pads was
      29% at 1 week , 62% at 6 weeks, 88% at 12 weeks, and 95% at 16 weeks. No patient
      in the series had a clinically significant leak or urinary retention.
      CONCLUSIONS: Our technique of the 'bimanual pinch' is easy to learn and has
      reduced the difficulty of bladder neck transection. It improved the outcome both
      during and after RRP in our series.

PMID- 16978280
TI  - The use of robotically assisted surgery for treating urachal anomalies.
AB  - OBJECTIVE: To report the management of urachal anomalies using a robotically
      assisted approach. PATIENTS AND METHODS: Between January 2005 and February 2006,
      five patients (mean age 51 years, range 24-68) were diagnosed with urachal
      anomalies. Two basic robot-assisted surgical approaches were used for excising
      the urachal anomalies: excision of the urachal remnant via partial cystectomy,
      and radical cystectomy for excision of urachal adenocarcinoma. RESULTS: All five
      cases were successful and the excised specimens were assessed histologically. The
      short-term oncological outcome in the three patients with histologically
      confirmed moderately differentiated adenocarcinoma showed no evidence of
      recurrent disease within a median interval of 8 months. Surveillance follow-up
      cystoscopy in the patients who had a partial cystectomy showed a well-healed
      bladder mucosa with no evidence of recurrence. CONCLUSIONS: Radical excision of
      the urachal tract with partial cystectomy or radical cystectomy using the da
      Vinci robot is safe, effective and technically feasible.

PMID- 16978281
TI  - Comparison of right and left laparoscopic live donor nephrectomy.
AB  - OBJECTIVE: To compare the anatomy and function of right and left kidneys
      retrieved by laparoscopic live donor nephrectomy (LDN). PATIENTS AND METHODS: In
      all, 84 transperitoneal LDNs were performed, 66 left and 18 right. Two different
      right-sided LDN techniques were used: initially, the inferior vena cava (IVC) was
      controlled with a Satinsky clamp introduced through a 6-8 cm right upper quadrant
      incision, through which the kidney was also removed (six patients). Subsequently,
      the IVC was completely mobilized by laparoscopic retrocaval dissection (in 12
      patients), allowing the use of a linear stapler-cutter, including the caval
      ostium with the renal vein. The kidney was then removed through a short
      Pfannenstiel incision. RESULTS: Left kidneys had longer renal veins (38 vs 27 mm;
      P < 0.05), but there were no differences in arterial length (32 vs 31 mm). Three
      right kidneys required back-table renal vein lengthening. The operative duration
      was shorter for right-sided LDNs (132 vs 182 min; P < 0.05). The serum creatinine
      level at 3 months was 131 vs 134 mmol/L for right and left kidneys, respectively.
      CONCLUSIONS: Despite faster surgery suggesting that the right LDN is technically
      easier, there is a greater need for back-table reconstruction of the renal vein.
      The functional results of right and left kidneys are equivalent.

PMID- 16978283
TI  - Injectable polydimethylsiloxane for treating incontinence in children with the
      exstrophy-epispadias complex: long-term results.
AB  - OBJECTIVE: To present our experience with the use of injectable
      polydimethylsiloxane (Macroplastique, Uroplasty, Minneapolis, MI, USA) for
      treating incontinence in children with the exstrophy-epispadias complex (EEC), as
      incontinence continues to be a challenging problem in such children, and although
      the primary management of EEC has developed over the last few decades, with early
      closure and reconstruction of the penis, achieving satisfactory continence status
      remains elusive. PATIENTS AND METHODS: We retrospectively reviewed the hospital
      records of 52 patients (41 boys and 11 girls, mean age at first injection 6.6
      years, range 3.6-16.7) with EEC who had injections with Macroplastique between
      January 1991 and February 2004; 34 had bladder exstrophy and 18 primary
      epispadias. For this study we defined success as complete dryness with no use of
      pads or nappies. Improvement was defined as being occasionally wet but with dry
      intervals lasting >or= 4 h. RESULTS: The mean (range) follow-up was 4.6 (0.5-9)
      years. Twenty patients had one injection, 10 had two, 13 had three, six had four,
      two had six and one had seven injections. In most patients a maximum of three
      injections predicted the outcome. The injection of Macroplastique was successful
      in nine patients (17%; with an annual follow-up, two at 1-2 years, three at 2-5
      years and four at >5 years), whilst 17 (33%) improved significantly (one at <1
      year, two at 1-2 years, eight at 2-5 years and six at >5 years). Those patients
      comprised five of 18 (27%) with epispadias and four of 34 (12%) with exstrophy. A
      history of previous surgery and gender had no significant effect on the outcome.
      Overall half the patients benefited from the procedure. CONCLUSIONS: This series
      confirms that injection with Macroplastique is minimally invasive, durable in
      significantly many patients and has a reasonable success rate. A history of
      previous surgery and gender had no significant effect on the outcome. Patients
      with epispadias are more likely to benefit from an injection with Macroplastique
      than those with bladder exstrophy. A maximum of three injections is predictive
      with reasonable certainty of any benefit from the procedure.

PMID- 16978282
TI  - The effect of nephroureterectomy on glomerular filtration rate.
AB  - OBJECTIVE: To determine the effect of nephroureterectomy (NU) on the glomerular
      filtration rate (GFR), and to determine whether the estimated GFR after NU is
      influenced by age and other factors associated with renal impairment. PATIENTS
      AND METHODS: We retrospectively identified 131 patients who had had a NU at
      either of two UK institutions. Their serum creatinine levels were recorded before
      and after NU, along with comorbidity data, and from this their GFR before and
      after NU was estimated using the Modification of Diet in Renal Disease Study
      Group equation. RESULTS: At a median follow-up of 5 years there was an 18%
      deterioration in estimated GFR in the 131 patients. The percentage deterioration
      in estimated GFR was greater in those aged >or= 70 years than in those aged <70
      years (20% vs 15% deterioration). Those with more risk factors for renal
      impairment had a greater percentage deterioration in estimated GFR than those
      with no such risk factors. CONCLUSIONS: This study shows that NU has a profound
      effect on future estimated GFR, an effect that is further compounded in those
      with risk factors for renal impairment. This study therefore provides both the
      patient and the urologist with an idea of potential future renal function after
      NU and contributes greatly to preoperative counselling.

PMID- 16978284
TI  - Analysis of anomalies of the epididymis and processus vaginalis in human fetuses
      and in patients with cryptorchidism treated and untreated with human chorionic
      gonadotrophin.
AB  - OBJECTIVE: To analyse the incidence of epididymal anomalies and the structure of
      the processus vaginalis (PV) in patients with cryptorchidism treated or not with
      human chorionic gonadotrophin (hCG), and to compare these findings with human
      fetuses with testes in the scrotum. PATIENTS, MATERIALS AND METHODS: We assessed
      24 fetuses with a gestational age of 23-35 weeks, and 114 cryptorchid patients
      (mean age 10.3 years). The patients were divided into two groups of those who
      used hCG (55, 65 testes) and those who did not (59, 75 testes). The sample was
      divided into six groups of possible anatomical relationships between the testis
      and the epididymis, according to a previous classification. Two situations were
      considered to analyse the PV: (a) total obliteration between the internal
      inguinal ring and the upper pole of the testis; and (b) total patency. RESULTS:
      Epididymal anomalies were found in 35% of patients with cryptorchidism and in
      only 4% of normal fetuses. Of the 47 cases of epididymal anomalies in patients
      with cryptorchidism 23 (49%) were treated with hCG and 24 (51%) were not. The PV
      was patent in 58% of patients with cryptorchidism and in only 5% of fetuses.
      Considering the three groups, the epididymal anomalies were more frequent when
      the PV was patent. CONCLUSIONS: Patency of the PV and the incidence of epididymal
      anomalies were more frequent in patients with cryptorchidism. The existence of
      epididymal anomalies did not influence testicular migration in patients treated
      with hCG.

PMID- 16978285
TI  - Ultrasonography to visualize the upper urinary tract in children with
      meningomyelocele.
AB  - OBJECTIVE: To evaluate the frequency of difficulties when using ultrasonography
      (US, commonly used to visualize the upper urinary tract) to evaluate renal length
      and dilatation in children and adolescents with meningomyelocele (MMC), who have
      excessive obesity or a distorted spine. PATIENTS AND METHODS: The records of all
      children with MMC investigated during 1996-2002 were assessed retrospectively and
      the last investigation used for analysis. In addition to the US results, the body
      mass index (BMI) and angulation of the spine were recorded. RESULTS: Of the 160
      children investigated, US was not evaluable in 46 (29%), i.e. in 35 (22%) for
      renal length, in one (1%) for dilatation and in 10 (6%) for both. In 99 patients
      with a straight spine and mild to moderate angulation, renal length was not
      measurable in 14 (14%), while dilatation was not evaluable in two (2%). In 61
      patients with a severely angled spine, the corresponding values were 31 (51%) and
      nine (15%), respectively. In eight patients with a BMI of >or= 27 kg/m2 and a
      straight spine, four of the investigations were not completely evaluable, while
      six were not in the eight patients with both a BMI of >or= 27 kg/m2 and severe
      angulation. CONCLUSION: Both severe spinal angulation and a BMI of >or= 27 kg/m2
      significantly reduced the possibility of evaluating the urinary tract by US.
      However, in an unselected group of children with MMC, dilatation could be
      evaluated in >90% and renal length in approximately 70%.

PMID- 16978286
TI  - Laparoscopic varicocele ligation in children and adolescents using isosulphan
      blue: a prospective randomized trial.
AB  - OBJECTIVES: To evaluate, in a randomized prospective trial in children and
      adolescents, the feasibility of isosulphan blue-based lymphatic vessel
      preservation during laparoscopic varicocelectomy and its impact on the
      complication rate, as the operative management of varicoceles remains
      controversial. PATIENTS AND METHODS: In all, 50 consecutive patients were
      randomly assigned to two laparoscopic varicocelectomy groups. The indications for
      surgery included scrotal pain and a difference in testicular size, as well as
      severe cosmetic impairment. All the patients had a laparoscopic varicocelectomy
      using three ports. Patients in group A had standard laparoscopy, while those in
      group B had additional isosulphan blue administered. After surgery, the patients
      were assessed at 3, 6 and 12 months for varicocele recurrence, hydrocele
      formation, atrophy, pain or other complications. RESULTS: There were no
      intraoperative complications or conversions to open surgery. There were no
      adverse reactions, scrotal haematomas or atrophy. At 3 months after surgery, the
      incidence of hydrocele in group A was 20% whereas in group B no hydroceles were
      detected (P = 0.025); at 6 months the 20% still had hydroceles. One patient in
      each group had varicocele recurrence associated with persistent pain. In two
      patients in group B, blue pigmentation of the left hemiscrotum persisted at the 3
      month follow-up but resolved by 6 months. CONCLUSIONS: Laparoscopic repair of
      varicoceles using isosulphan blue helps to identify and preserve the lymphatic
      drainage. It prevents secondary hydrocele formation, the most common
      complication, with no supplementary risk to the patient. Also, testicular oedema
      causing impaired spermatogenesis can be avoided.

PMID- 16978287
TI  - The role of Ca2+ influx and intracellular Ca2+ release in the muscarinic-mediated
      contraction of mammalian urinary bladder smooth muscle.
AB  - OBJECTIVE To study the involvement of extracellular Ca2+ and the properties of
      the intracellular Ca2+ ([Ca2+]i) stores on the carbachol-induced contraction of
      mammalian urinary bladder smooth muscle strips under polarized and depolarized
      conditions. MATERIALS AND METHODS: Strips of bladder were suspended between
      platinum ring electrodes in a cylindrical organ bath (0.2 mL) and continuously
      superfused with Krebs' solution at 1 mL/min. The effect of nifedipine,
      cyclopiazonic acid (CPA), thapsigargin, procaine, ryanodine and caffeine before
      and during a 10-s application of 100 microm carbachol under polarized conditions
      were studied. The effect of these drugs was also assessed under depolarized
      conditions using a protocol that allowed a more detailed assessment of the role
      of [Ca2+]i stores, consisting of emptying the stores by exposure to Ca2+-free
      solution, rapidly refilling them by a 10-s application of 81.5 mm Ca2+ (priming),
      returning to the Ca2+-free solution for 3 min and then applying 100 microm
      carbachol (10 s) in Ca2+-free solution (store release). RESULTS: Under polarized
      conditions, nifedipine and Ca2+ removal almost completely inhibited the carbachol
      induced contractions. CPA increased the amplitude and duration of both carbachol-
      and electrical field stimulation-induced contractions. Although ryanodine had no
      inhibitory effect, caffeine and procaine significantly inhibited the carbachol
      induced contraction. Under depolarized conditions nifedipine blocked both priming
      and store release contractions. CPA, thapsigargin, procaine and ryanodine
      significantly increased the priming and inhibited the store release contractions.
      However, caffeine virtually abolished both priming and store release
      contractions. CONCLUSION: These results suggest that in guinea-pig urinary
      bladder smooth muscle the Ca2+ necessary for contraction enters the cell through
      voltage-dependent dihydropyridine-sensitive Ca2+ channels and is pumped into an
      intracellular store that is released by carbachol. Under polarized conditions,
      the blockade of sarco-endoplasmic reticulum calcium ATP-ase (SERCA) with CPA
      increases [Ca2+]i and carbachol-induced contractions. The effects of caffeine and
      procaine suggest that store release involves ryanodine receptors and calcium
      induced calcium release. Under depolarized conditions, Ca2+ entry is blocked by
      nifedipine and the stores diminish. Stored Ca2+ is also greatly reduced by the
      blockade of SERCA with either CPA or thapsigargin. Procaine, ryanodine and
      caffeine blocked the store release contractions, suggesting that this involves
      ryanodine receptors and calcium-induced calcium release.

PMID- 16978288
TI  - Gene expression profiles in mouse urethral development.
AB  - OBJECTIVE: To analyse the gene expression profiles of the mouse genital tubercle
      (GT) during urethral tube development at embryonic (E) days E14, E15, E16 and
      E17, as the aetiology of hypospadias, one of the most common congenital
      anomalies, remains unknown. MATERIALS AND METHODS: During GT development the
      urethral folds fuse to form an epithelial seam; subsequently, the epithelial seam
      disappears, resulting in the normal tubular urethra. Abnormalities in urethral
      seam formation and remodelling might explain hypospadias, and elucidating the
      molecular developmental mechanisms underlying normal penile development might
      provide the basis for understanding hypospadias. Total RNA was isolated from the
      genital tubercle at embryonic days E14, E15, E16, and E17. Together with
      reference RNA, sample RNA was labelled with Cy-3 and Cy-5 respectively and
      hybridized to a 16 000-mouse gene array that included the Incyte GEM2.1 and NIA
      7k sets. Candidate genes were analysed by immunohistochemistry and real-time
      polymerase chain reaction. RESULTS: Using cDNA microarrays, we identified the up
      regulation of genes involved in the transforming growth factor (TGF)-beta and Wnt
      Frizzled pathways, and of thrombospondin (TSP) 4, a member of a cell-migration
      molecule family, all candidates for involvement in urethral tube formation.
      Immunohistochemistry showed TGFbeta1, TGFbeta receptor III, and Frizzled1 were
      expressed exclusively in E14-E17 urethral epithelium. TSP4 was expressed in the
      mesenchymal basal layer underlying E17 GT skin epidermis. CONCLUSIONS: Many
      signalling pathways are involved in late GT development, and cell migration
      molecules might have an important role in urethral tube formation.

PMID- 16978289
TI  - Gene expression profiling of the human prostate zones.
AB  - OBJECTIVE: To investigate differences in gene expression in different zones of
      the prostate by microarray analyses, to better understand why aggressive tumours
      predominantly occur in the peripheral zone (PZ), whereas benign prostatic
      hyperplasia (BPH) occurs almost exclusively in the transition zone (TZ).
      MATERIALS AND METHODS: Expression profiling of both prostate zones was done by
      microarray analysis. Reverse transcription-polymerase chain reaction (RT-PCR) of
      the top 18 genes confirmed the microarray analyses. RT-PCR with common cell-type
      markers indicated that the differential expression between the zones was not
      caused by an unequal distribution of different cell types. Primary stromal and
      epithelial prostate cells were used to study cell type expression in the 12
      highest differentially expressed zonal-specific genes. RESULTS: In all, 346 genes
      were identified as preferentially expressed in the TZ or PZ. A few of the TZ
      specific genes, including ASPA, FLJ10970 and COCH, were also stroma-specific.
      Comparisons with other microarray studies showed that gene expression profiles of
      prostate cancer and BPH correlate with the expression profiles of the PZ and TZ,
      respectively. CONCLUSION: Gene expression differs between the PZ and TZ of the
      prostate, and stromal-epithelial interactions might be responsible for the
      distinct zonal localization of prostate diseases.

PMID- 16978290
TI  - LRIG1, a candidate tumour-suppressor gene in human bladder cancer cell line
      BIU87.
AB  - OBJECTIVES: To determine the effects of LRIG1 on the growth, migration and
      invasion of bladder cancer cells and the mechanisms underlying such effects.
      MATERIALS AND METHODS: The plasmid pLRIG1-green fluorescence protein (GFP) was
      transfected into BIU87 bladder cancer cells by Lipofectamine2000 (Invitrogen,
      Groningen, the Netherlands), and the cells that expressed LRIG1 stably were
      screened out by G418. The changes in LRIG1 and epidermal growth factor receptor
      (EGFR) protein levels were measured by Western blot; growth curves were estimated
      by the tetrazolium (MTT) assay; then cell-cell adhesion, cell-matrix adhesion and
      cell invasion assays were used to measure proliferation, adhesion and invasion in
      LGIR1-transfected and control cells. RESULTS: The LRIG1 protein level in pLRIG1
      GFP transfected cells was significantly higher than that in control cells, while
      the EGFR protein level was significantly lower. pLRIG1-GFP transfected cells had
      less proliferation than control cells. Contrasting with non-LRIG1-transfected
      cells, the invasion and cell-matrix adhesion ability of pLRIG1-GFP transfected
      cells decreased markedly, and conversely the homotypic cell-cell adhesion ability
      was significantly higher. CONCLUSIONS: LRIG1 might act as a tumour-suppressor
      gene, participating in negative feedback control of EGFR expression, which
      inhibits bladder cancer cells from growth, migration and invasion.

PMID- 16978291
TI  - The role of the lymphatic system and its specific growth factor, vascular
      endothelial growth factor C, for lymphogenic metastasis in prostate cancer.
AB  - OBJECTIVE: To compare prostate carcinoma, with and with no lymph node metastasis,
      to benign prostatic hyperplasia (BPH) tissue for lymphatic vessel density (LVD)
      and the expression of the lymph-endothelial specific growth factor, vascular
      endothelial growth factor C (VEGF-C), to determine their role in lymphogenic
      metastasis. PATIENTS, MATERIALS AND METHODS: Lymphatic vessels were stained using
      lymphatic vessel endothelial hyaluronan receptor 1 and assessed in standard
      areas. The expression of VEGF-C was assessed by the number of positive epithelial
      cells. The data were compared with the clinical staging. RESULTS: The lowest LVD
      was found in tumorous areas as opposed to periphery and nontumorous tissue (P =
      0.007; P < 0.001). The highest LVD was in BPH tissue (P < 0.001). There was no
      correlation with clinical staging. There was more VEGF-C staining in pN1 than in
      pN0 and in BPH specimens (P = 0.002). CONCLUSION: LVD is not a prognostic
      variable for the process of lymphogenic metastasis in prostate cancer. VEGF-C is
      up-regulated in prostate cancer and its correlation with lymph node status
      suggests a role for the development of lymph node metastasis, e.g. via an
      increased permeability of lymphatic vessels.

PMID- 16978292
TI  - Prostate cells exposed to lycopene in vitro liberate lycopene-enriched exosomes.
AB  - OBJECTIVES: To investigate whether cellular exosomes liberated by prostatic cell
      lines in culture might be acting as the transport vehicles for the dietary
      antioxidant lycopene, known to be sequestered in the prostate gland and to reduce
      the risk of developing benign prostatic hyperplasia (BPH) and prostate cancer;
      its subsequent secretion into seminal plasma also confers protection to
      spermatozoa against oxidative free-radical damage. MATERIALS AND METHODS: Using
      benign and malignant human prostatic cell culture models, we assessed the role
      that their exosomes (the putative in vitro analogues of prostasomes) might have
      in the transport of lycopene. RESULTS: Cells exposed to lycopene in vitro
      accumulated the molecule and secrete lycopene-enriched exosomes. This continued
      after the lycopene exposure was stopped. Extraction of lycopene from the
      exosomes, followed by high-performance liquid chromatography, confirmed nanogram
      quantities of lycopene per milligram of exosomal protein. Packaging into exosomes
      for export resulted in reduced degradation of this labile antioxidant, and
      therefore maximized the effectiveness of delivery to the sites of action.
      CONCLUSION: These results support the likelihood that these organelles act as the
      transport vehicles for this important lipophilic agent known to have a role in
      the chemoprevention of various urological pathologies such as BPH, prostate
      cancer and male infertility.

PMID- 16978293
TI  - The economics of drug development in prostate cancer.

PMID- 16978294
TI  - Predictive factors of resolution of primary vesico-ureteric reflux: a
      multivariate analysis.

PMID- 16978295
TI  - Endoluminal occlusion of the inferior vena cava in renal cell carcinoma with
      retro- or suprahepatic caval thrombus.

PMID- 16978296
TI  - The use of duloxetine for stress incontinence after prostatectomy.

PMID- 16978297
TI  - Surgical management of penile carcinoma: the primary lesion.

PMID- 16978298
TI  - An audit of implanted penile prostheses in the UK.

PMID- 16978299
TI  - Comparison of standard transurethral resection, transurethral vapour resection
      and holmium laser enucleation of the prostate for managing benign prostatic
      hyperplasia of >40 g.

PMID- 16978300
TI  - Further experience with laparoscopic nephrectomy for Wilms' tumour after
      chemotherapy.

PMID- 16978302
TI  - Surgical atlas. Transurethral resection of the prostate.

PMID- 16978303
TI  - Cricothyroidotomy; time for change.

PMID- 16978304
TI  - Acute peri-operative beta blockade in intermediate-risk patients.
AB  - Peri-operative beta-blockade has been shown to reduce the incidence of
      postoperative cardio- vascular complications including cardiac death in high-risk
      non-cardiac surgical patients. However, the recent analysis by Lindenauer et al.
      suggests that it is inappropriate to administer beta-blockers blindly to all
      surgical patients. In an attempt to determine the appropriateness of peri
      operative beta-blocker administration across patients with a spectrum of
      cardiovascular risks, we have examined studies of intermediate-risk patient
      groups (that is those undergoing intermediate risk surgery or those with a Lee
      Revised Cardiac Risk Score of < or =2). We analysed data from randomised
      prospective studies of the effects of acute peri-operative beta-blockade on the
      incidence of peri-operative myocardial ischaemia. By examining the demographics
      and surgical interventions in these patients, we have compared these studies with
      other studies of peri-operative silent myocardial ischaemia representing patients
      of similar risk. We thus estimated the expected long-term postoperative
      cardiovascular complication rate associated with myocardial ischaemia in these
      patients in terms of number needed to treat for ischaemia prevention and for
      prevention of major cardiovascular complications. Prevention of peri-operative
      myocardial ischaemia with acute beta-blockade in non-cardiac surgical patients
      with 1-2 RCRI clinical risk factors can be achieved with a number needed to treat
      of 10. It is not associated with a significant increase in drug associated side
      effects. However, acute beta-blockade shows no real benefit in the prevention of
      major cardiovascular complications in intermediate risk non-vascular surgical
      patients with a number-needed-to-treat of 833. Vascular surgical patients
      undergoing intermediate-risk surgery may benefit from the protective effects of
      acute peri-operative beta-blockade, however, with a number-needed-to-treat of 68
      it would require a randomised clinical trial of over 24,000 patients to prove
      their efficacy.

PMID- 16978305
TI  - Fentanyl and clonidine as adjunctive analgesics with levobupivacaine in
      paravertebral analgesia for breast surgery.
AB  - The addition of fentanyl or clonidine to levobupivacaine was evaluated in
      patients undergoing breast surgery under general anaesthesia with intra- and
      postoperative paravertebral analgesia. Patients were randomly allocated to four
      groups: Group L received 19 ml bolus levobupivacaine 0.25% plus 1 ml saline
      followed by an infusion of levobupivacaine 0.1%; Group LF received 19 ml bolus
      levobupivacaine 0.25% plus fentanyl 50 microg followed by an infusion of
      levobupivacaine 0.05% with fentanyl 4 microg x ml(-1); Group LC received 19 ml
      bolus levobupivacaine 0.25% plus clonidine 150 microg followed by an infusion of
      levobupivacaine 0.05% with clonidine 3 microg x ml(-1); Group C (control)
      received general anaesthesia without paravertebral analgesia. All groups received
      postoperative i.v. morphine patient controlled analgesia (PCA). Although mean
      (SD) postoperative PCA morphine consumption was decreased in LF [7.9 (4.1) mg]
      and LC [5.9 (3.5) mg]vs L [27.7 (8.6) mg] or C patients [21.7 (5.5) mg], p <
      0.01, paravertebral fentanyl and clonidine were associated with significantly
      increased vomiting and hypotension, respectively.

PMID- 16978306
TI  - Association between vasopressor dependence and early outcome in patients after
      cardiac surgery.
AB  - Arterial hypotension with vasopressor dependence is a major problem after cardiac
      surgery. We evaluated the early postoperative course of 1558 consecutive patients
      scheduled for cardiac surgery, and compared the outcome of patients with and
      without vasopressor dependence (defined as the need for > 0.1 microg x kg(-1) x
      h(-1) noradrenaline for > 3 h in the face of normovolaemia). Vasopressor
      dependence was diagnosed in 424 patients (27%) and was associated with a higher
      incidence of postoperative renal failure (67 (15.7%) vs 7 (0.6%), respectively; p
      < 0.0001), a longer duration of ventilation (median IQR [range]) 14 (8-26 [6-39])
      h vs 8 (5-11 [4-32]) h; p < 0.0001), a greater need for red cell transfusion (3
      (1-5 [0-10]) units vs 1 (0-2 [0-4]) units; p < 0.001) and a longer length of stay
      in the ICU (4 (2-6 [2-9] days) vs 2 (1-3 [1-6] days; p < 0.001). Vasopressor
      dependence could be predicted from a combination of factors, including pre
      operative ejection fraction < 37%, cardiopulmonary bypass lasting > 94 min, and
      postoperative interleukin-6 > 837 pg x ml(-1).

PMID- 16978307
TI  - An observational study of practice during transfer of patients from anaesthetic
      room to operating theatre.
AB  - We observed practice during transfer of 80 patients from anaesthetic room to
      operating theatre, to determine the duration of apnoea and the time without
      monitoring during the transfer process. Median (IQR [range]) time from
      disconnection of the breathing system in the anaesthetic room to the first breath
      in theatre was 54 (44-65 [27-196]) s, and from disconnection of the pulse
      oximetry probe to the first reading in theatre was 90 (74-103 [44-182]) s. In
      four patients (5%) arterial oxygen saturation fell to 94%, with the greatest
      desaturation observed 11%. The transfer process may represent a window of
      opportunity for the occurrence of harm or the first step in a chain of events
      leading to harm, and is difficult to justify on patient safety grounds.

PMID- 16978308
TI  - Determination of the optimal angle for needle insertion during caudal block in
      children using ultrasound imaging.
AB  - Using ultrasound imaging, the optimal angle for needle insertion during caudal
      epidural injection in children was estimated. After general anaesthesia,
      ultrasonography was performed at the sacral hiatus in 130 children aged 2-84
      months positioned in the lateral position. The median [range] values for the
      intercornual, caudal space depth and the distance from skin to the posterior
      sacral bony surface were 17.0 [9.6-24] mm, 3.5 [1-8] mm and 21.0 [10-39] mm,
      respectively. The optimal angle showed no significant correlation with age,
      weight, height or body surface area. The median [range] calculated optimal angle
      for the needle was 21.0 [10-38] degrees. We conclude that the needle should be
      inserted at about 20 degrees to the skin to avoid puncture of the bone and
      potential intra-osseous injection.

PMID- 16978309
TI  - A national survey of intensive care follow-up clinics.
AB  - Intensive care follow-up clinics allow extended review of survivors of critical
      illness. However, the current provision of intensive care follow-up clinics in
      the UK is unknown. We performed a survey of intensive care follow-up clinic
      practice in the UK. A questionnaire was sent to 298 intensive care units in the
      UK to determine the number of follow-up clinics and details of current follow-up
      practice. Responses were received from 266 intensive care units, an 89% response
      rate. Eighty units (30%) ran a follow-up clinic. Only 47 (59%) of these clinics
      were funded. Of those intensive care units without a follow-up clinic, 158 (88%)
      cited 'financial constraints' as the reason. Over half of the follow-up clinics
      (44 clinics, 55%) were nurse-led, and the majority (56 clinics, 77%) only
      routinely review patients treated on the intensive care unit for 3 or 4 days or
      longer. Nearly half of the follow-up clinics (39 clinics, 49%) have pre
      negotiated access to at least one other out-patient service.

PMID- 16978310
TI  - Target ranges and the apparent compliance with tight glycaemic control.
AB  - We performed a retrospective audit of blood glucose control after introducing a
      new protocol for insulin infusion. The audit showed a sustained reduction in the
      median blood glucose, which decreased from 7.0 to 6.8 mmol x l(-1), primarily
      because of a reduction in the proportion of values above 6 mmol x l(-1). When we
      examined the proportion of readings with previously published 'acceptable' ranges
      we found that small, probably clinically insignificant, changes in the accepted
      range have a major effect on apparent compliance with glycaemic control. This is
      because a large number of results fall within a narrow range of values. As a
      result there is a nearly 2.5-fold difference in compliance for a change in the
      upper limit of the target range of just 2.2 mmol x l(-1). Different target ranges
      have been recommended for tight glycaemic control. When comparing compliance with
      tight glycaemic control between intensive care units, target ranges should be
      identical.

PMID- 16978311
TI  - Touch sensitivity with sterile standard surgical gloves and single-use protective
      gloves.
AB  - The purpose of this study was to evaluate touch sensitivity and static two-point
      discrimination of the dominant index and middle finger in 20 anaesthetists
      wearing no gloves, single-use protective gloves or sterile standard surgical
      gloves. Semmes-Weinstein filaments were used to measure cutaneous pressure
      thresholds, and a Two-Point-Discriminator to estimate static two-point
      discrimination. Wearing gloves significantly reduced touch sensitivity (p <
      0.01), but not two-point discrimination. No difference in touch sensitivity or
      two-point discrimination was found between different types of gloves. The results
      of our study suggest that the additional cost of sterile standard surgical gloves
      can not be justified in terms of touch sensitivity.

PMID- 16978312
TI  - Needle vs surgical cricothyroidotomy: a short cut to effective ventilation.
AB  - Cricothyroidotomy can be performed using three techniques. This literature review
      seeks to determine which is more appropriate for use in prehospital can't
      intubate/can't ventilate scenarios where laryngeal mask airways prove
      ineffective. The common approach of inserting a 14-gauge cannula and using low
      pressure ventilation via intermittent occlusion of an opening in oxygen tubing
      (15 l x min(-1) flow) results in ineffective ventilation within 60 s or less,
      depending on the degree of airway obstruction. In the absence of a high degree of
      upper airway obstruction, ventilation can be effective if the cannula is attached
      to a high pressure (45 psi) jet ventilator, but such devices are rare in UK
      prehospital practice. A self-inflating bag used with a cuffed tube inserted
      through a horizontal scalpel incision provides sustained adequate ventilation,
      has a relatively low complication rate compared to needle cricothyroidotomy and
      is a skill that can be easily taught to paramedics, nurses and doctors.

PMID- 16978313
TI  - The LMA CTrach in airway resuscitation: six case reports.
AB  - We report six patients with unexpected difficult airways who underwent tracheal
      intubation using the Laryngeal Mask Airway CTrach. All these patients had failed
      orotracheal intubation using direct laryngoscopy and gum elastic bougie
      placement. Fibreoptic bronchoscopy failed in two of these patients due to blood
      and secretions in the airway. This report describes the successful use of this
      new intubating laryngeal mask in these cases, all of whom were intubated on the
      first attempt with this new device.

PMID- 16978314
TI  - An in vitro study of the compliance of paediatric tracheal tube cuffs and
      tracheal wall pressure.
AB  - Cuff volume-pressure curves and cuff pressure-tracheal wall pressure
      relationships were investigated in eight brands of currently available cuffed,
      paediatric tracheal tubes with internal diameters of 5.0 mm. Cuff volume-pressure
      curves were measured with the cuff unrestricted and with the cuff placed within a
      tracheal model with wall pressure measurements. With the tracheal tube cuffs,
      unrestricted cuff compliance at 20 cmH(2)O cuff pressure varied between 0.06 and
      0.3 ml x cmH(2)O(-1). With the cuff restricted within the model trachea, all
      tracheal tube cuffs became considerably less compliant (0.01-0.09 ml x cmH(2)O(
      1)). We found tracheal wall pressure was similar to the cuff pressure as long as
      the resulting cuff diameter was sufficiently large freely to drape the inner
      tracheal wall. We found that, regardless of whether a higher or lower compliant
      tube cuff was used, cuff hyperinflation uniformly resulted in potentially
      compromised tracheal mucosal blood flow; cuff pressure monitoring using cuff
      pressure limitation is therefore strongly recommended.

PMID- 16978315
TI  - The history of extracorporeal oxygenators.
AB  - Extracorporeal oxygenators are artificial devices that substitute for anatomical
      lungs by delivering oxygen to, and extracting carbon dioxide from, blood. They
      were first conceptualised by the English scientist Robert Hooke (1635-1703) and
      developed into practical extracorporeal oxygenators by French and German
      experimental physiologists in the 19th century. Indeed, most of the
      extracorporeal oxygenators used until the late 1970s were derived from von
      Schroder's 1882 bubble oxygenator and Frey and Gruber's 1885 film oxygenator. As
      there is no intervening barrier between blood and oxygen, these are called
      'direct contact' oxygenators; they contributed significantly to the development
      and practice of cardiac surgery till the 1980s. Membrane extracorporeal
      oxygenators introduce a gas-permeable interface between blood and oxygen. This
      greatly decreased the blood trauma of direct-contact extracorporeal oxygenators,
      and enabled extracorporeal oxygenators to be used in longer-term applications
      such as the intensive therapy of respiratory distress syndrome; this was
      demonstrably beneficial for neonates but less so for older patients. Much work
      since the 1960s focused on overcoming the gas exchange handicap of the membrane
      barrier, leading to the development of high-performance microporous hollow-fibre
      oxygenators that eventually replaced direct-contact oxygenators in cardiac
      theatres.

PMID- 16978316
TI  - Peri-operative trans-oesophageal echocardiography and nitric oxide during general
      anaesthesia in a patient with Eisenmenger's syndrome.
AB  - We describe the peri-operative care of a patient with Eisenmenger's syndrome
      presenting for laparotomy. These patients require techniques to prevent the
      potential increase in intracardiac shunt caused by anaesthesia, by minimising
      increases in pulmonary artery pressure and reductions in systemic vascular
      resistance. The successful use of combined epidural and general anaesthesia with
      elective use of inhaled nitric oxide as a pulmonary vasodilator, and intra
      operative trans-oesophageal echocardiography is described.

PMID- 16978317
TI  - Use of continuous positive airway pressure during spinal anaesthesia in a patient
      with severe chronic obstructive pulmonary disease.
AB  - We report the case of a patient with severe chronic obstructive pulmonary disease
      who underwent local resection of a carcinoma of the rectum under spinal
      anaesthesia. Although the patient was keen to avoid general anaesthesia and to
      have the operation under a spinal anaesthetic, pre-operative assessment showed
      that he could not lie flat. As the surgical procedure required the patient to be
      in the lithotomy position, ideally with a head-down tilt, it was hoped that
      continuous positive airway pressure with a facemask during spinal anaesthesia
      might help him to tolerate the position comfortably. Continuous positive airway
      pressure at 7.5 cmH(2)O was successfully used to facilitate breathing during
      surgery under spinal anaesthesia. A combination of regional anaesthesia and
      continuous positive airway pressure via a facemask is easy to use and may be a
      useful option in the management of these challenging patients.

PMID- 16978318
TI  - Hereditary neuropathy with liability to pressure palsies and anaesthesia: peri
      operative nerve injury.
AB  - A 43-year-old female with carcinoma of the left breast underwent wide local
      excision of the tumour and sentinel lymph node biopsy under general anaesthesia.
      Three lymph nodes were removed uneventfully during the operation.
      Postoperatively, the patient complained of weakness and decreased sensation of
      her left arm. A diagnosis of peri-operative neuropraxia was made. This resolved
      completely over the following 4 weeks. Genetic testing confirmed a diagnosis of
      hereditary neuropathy with liability to pressure palsies.

PMID- 16978319
TI  - Epidural clonidine for total hip replacement.

PMID- 16978321
TI  - Automated calculation of 'early warning scores'.

PMID- 16978323
TI  - Massive obstetric haemorrhage: arterial embolisation vs rFVIIa.

PMID- 16978325
TI  - Awake fibrecapnic intubation.

PMID- 16978326
TI  - Ultra-low dose CSE.

PMID- 16978327
TI  - Direct laryngoscopy after fibreoptic intubation.

PMID- 16978328
TI  - Methylene blue implicated in potentially fatal serotonin toxicity.

PMID- 16978330
TI  - GlideScope-assisted awake fibreoptic intubation: initial experience in 13
      patients.

PMID- 16978331
TI  - Pharyngeal oxygen insufflation via the laryngoscope blade.

PMID- 16978332
TI  - The LMA Ctrach for unanticipated difficult intubation.

PMID- 16978333
TI  - The effect of temperature on baricity of local anaesthetic solutions.

PMID- 16978334
TI  - Combining care bundles: a potential hazard of sedation interruption and tight
      glucose control.

PMID- 16978335
TI  - Problem with pump set for Hospira Pain Management pump.

PMID- 16978336
TI  - Ultrasound diagnosis of a false radial artery aneurysm in ICU.

PMID- 16978339
TI  - A response to 'A national survey of epidural use and management in elderly
      patients undergoing elective and emergency laparotomy'.

PMID- 16978340
TI  - A response to 'Obesity and obstetric anaesthesia'.

PMID- 16978342
TI  - A response to 'Incidence and significance of errors in a patient 'track and
      trigger' system during an epidemic of Legionnaires' disease: retrospective case
      note analysis'.

PMID- 16978343
TI  - A response to 'Obesity and obstetric anaesthesia'.

PMID- 16978345
TI  - John Stanley Mornington Zorab.

PMID- 16978346
TI  - Bacterial lateral flagella: an inducible flagella system.
AB  - Flagella are complex surface organelles that allow bacteria to move towards
      favourable environments and that contribute to the virulence of pathogenic
      bacteria through adhesion and biofilm formation on host surfaces. There are a few
      bacteria that possess functional dual flagella systems, such as Vibrio
      parahaemolyticus, some mesophilic Aeromonas spp., Rhodospirillum centenum and
      Azospirillum brasilense. These bacteria are able to express both a constitutive
      polar flagellum required for swimming motility and a separate lateral flagella
      system that is induced in viscous media or on surfaces and is essential for
      swarming motility. As flagella synthesis and motility have a high metabolic cost
      for the bacterium, the expression of the inducible lateral flagella system is
      highly regulated by a number of environmental factors and regulators.

PMID- 16978347
TI  - Functional expression of the particulate methane mono-oxygenase gene in
      recombinant Rhodococcus erythropolis.
AB  - In order to construct an expression system for the particulate methane mono
      oxygenase (pMMO) gene (pmo), the structural gene cluster pmoCAB amplified from
      Methylosinus trichosporium OB3b was inserted into a shuttle vector pBS305 under
      the control of a dsz promoter and transformed into Rhodococcus erythropolis LSSE8
      1. A stable transformant was successfully obtained using ethane as the sole
      carbon source. Fluorescence in situ hybridization results showed that the dsz
      promoter allowed the pmo genes to be transcribed in the recombinant strain. The
      effects of Cu2+ and Zn2+ concentrations on cell growth and pMMO activity in
      ethane-containing medium were examined. It was discovered that 7.5 microM Cu2+
      and 1.8 microM Zn2+ were suitable to achieve high cell concentration and pMMO
      activity, but the amount of methanol accumulated during methane oxidation by the
      recombinant strain was still low.

PMID- 16978348
TI  - Partial rpoB gene sequencing for identification of Leptospira species.
AB  - The usual target for sequence-based identification of Leptospira species is the
      16S rRNA gene. However, because the 16S rRNA gene is not polymorphic enough, it
      is necessary to sequence a 1500 bp segment of this gene for accurate
      identification. Based on the alignment of previously determined rpoB of three
      Leptospira strains, we designed and tested a primer pair that enabled us to
      amplify and sequence a 600 bp segment of Leptospira rpoB. This segment was
      species-specific for the 16 species tested, but was unable to separate Leptospira
      interrogans serovars accurately. For the 11 L. interrogans serovars tested, only
      seven genotypes could be determined. We thus think that analysis of partial rpoB
      may be useful as an initial screening test for the identification of a new
      isolate of Leptospira and detection or identification of Leptospira in clinical
      or environmental samples, but not for serovar determination.

PMID- 16978349
TI  - The presence of major world-wide clones for phage type 4 and 8 Salmonella
      enterica serovar Enteritidis and the evaluation of their virulence levels by
      invasiveness assays in vitro and in vivo.
AB  - Seventy-seven animal isolates of Salmonella enterica serovar Enteritidis (S.
      Enteritidis) obtained from the United States were analyzed by phage typing and
      pulsed field gel electrophoresis (PFGE). Thirty-nine strains were found with
      phage types (PT) 4, 8, and 13a. When the chromosomal DNA of these 39 isolated
      strains with PT4, 8, and 13a were digested with XbaI, SpeI and NotI, followed by
      PFGE analysis, 28 strains were found with a pattern combination of X4S4N4, which
      was the major subtype. When PFGE patterns of the US isolates with PT 4 and 8 were
      compared with those of the Taiwanese and German isolates, pattern X3S3N3 was
      confirmed to be the world-wide subtype shared by PT 4 isolates, as previously
      reported, while pattern X4S4N4 was newly found to be the most common subtype
      shared by PT 8 strains. The presence of such major world-wide clones, however,
      does not necessarily mean that these clones are highly virulent, at least not
      according to the results of invasiveness assays using cultured human intestinal
      epithelium cell line Int-407 and living BALB/mice.

PMID- 16978350
TI  - Isolation and characterization of a denitrifying monocrotophos-degrading
      Paracoccus sp. M-1.
AB  - A bacterium strain, which is capable of degrading monocrotophos, was isolated
      from sludge collected from the bottom of a wastewater treatment system of a
      chemical factory, and named M-1. On the basis of the results of the cellular
      morphology, physiological and chemotaxonomic characteristics and phylogenetic
      similarity of 16S rDNA gene sequences, the strain was identified as a Paracoccus
      sp. The ability of the strain to mineralize monocrotophos was investigated under
      different culture conditions. Other organophosphorus insecticides and amide
      herbicides were also degraded by M-1. The key enzyme (s) involved in the initial
      biodegradation of monocrotophos in M-1 was shown to be a constitutively expressed
      cytosolic protein. The addition of M-1 (10(6) CFU g(-1)) to fluvo-aquic soil and
      a high-sand soil containing monocrotophos (50 mg kg(-1)) resulted in a higher
      degradation rate than that obtained from noninoculated soil. This microbial
      culture has great potential utility for the bioremediation of wastewater or soil
      contaminated with organophosphorus pesticides and amide herbicides.

PMID- 16978351
TI  - Occurance of Staphylococcus nepalensis strains in different sources including
      human clinical material.
AB  - Five isolates of coagulase-negative staphylococci were obtained from human urine,
      the gastrointestinal tract of squirrel monkeys, pig skin and from the
      environment. All key biochemical characteristics of the tested strains
      corresponded with the description of Staphylococcus xylosus species. However,
      partial 16S rRNA gene sequences obtained from analysed strains corresponded with
      those of Staphylococcus nepalensis reference strains, except for two strains
      which differed in one residue. Ribotyping with EcoRI and HindIII restriction
      enzymes, whole cell protein profile analysis performed by SDS-PAGE and SmaI
      macrorestriction analysis were used for more precise characterization and
      identification of the analysed strains. Obtained results showed that EcoRI and
      HindIII ribotyping and whole cell protein fingerprinting are suitable and
      reliable methods for the differentiation of S. nepalensis strains from the other
      novobiocin resistant staphylococci, whereas macrorestriction analysis was found
      to be a good tool for strain typing. The isolation of S. nepalensis is sporadic,
      and according to our best knowledge this study is the first report of the
      occurrence of this species in human clinical material as well as in other
      sources.

PMID- 16978352
TI  - Influence of environmental conditions on putisolvins I and II production in
      Pseudomonas putida strain PCL1445.
AB  - Pseudomonas putida strain PCL1445 produces the cyclic lipopeptides putisolvin I
      and II, which are biosurfactants affecting environmentally important functions
      including swarming motility, solubility of nutrients and biofilm formation and
      maintenance. In this study, the effect of relevant nutritional and environmental
      factors on putisolvin production by PCL1445 was analyzed. Growth and levels of
      putisolvins I and II biosynthesis were significantly influenced by various carbon
      sources and by the nature of amino acid supplemented to the culture medium. An
      increase in the salt concentration of BM medium as well as growth at 1% oxygen
      significantly increased putisolvin production. In addition, we recently
      demonstrated that growth at a low temperature has a positive effect on putisolvin
      production. Analysis of the expression of gacA and gacS in Tn5luxAB mutant
      strains at a low temperature or under a high salt concentration suggests that
      biosynthesis of putisolvin is modulated through the GacA/GacS two-component
      regulatory system in PCL1445 under the tested conditions.

PMID- 16978353
TI  - Disappearance of oxytetracycline resistance genes in aquatic systems.
AB  - The disappearance of selected tetracycline resistance genes was investigated in
      different simulated receiving waters to determine conditions that maximize
      resistance gene loss after release. Wastewater from an operating cattle feedlot
      lagoon was provided to four pairs of duplicate 3-L flasks, and tet(O), tet(W),
      tet(M), tet(Q), and 16S rRNA gene levels were monitored over 29 days using real
      time PCR. Treatments included simulated sunlight with 0, 25, and 250 microg L(-1)
      nominal oxytetracycline (OTC) levels, respectively, and 'dark' conditions. Gene
      disappearance rates were always highest when light was present, regardless of OTC
      level. First-order loss coefficients (k(d)) for the sum of resistance genes were
      0.84, 0.75, and 0.81 day(-1) for 0.0, 25, and 250 microg L(-1) OTC treatments
      over the first 7 days after release, respectively, whereas k(d) was 0.49 day(-1)
      under dark conditions, which is significantly lower (P<0.10). k(d) varied
      fourfold among the four individual genes, although disappearance patterns were
      similar among genes. Results suggest that light exposure should be maximized in
      receiving waters in order to maximize resistance gene loss rate after release.

PMID- 16978354
TI  - Effects of yeast proteolytic activity on Oenococcus oeni and malolactic
      fermentation.
AB  - Alcoholic fermentation of synthetic must was performed using either Saccharomyces
      cerevisiae or a mutant Deltapep4, which is deleted for the proteinase A gene.
      Fermentation with the mutant Deltapep4 resulted in 61% lower levels of free amino
      acids, and in 62% lower peptide concentrations at the end of alcoholic
      fermentation than in the control. Qualitative differences in amino acid
      composition were observed. Changes observed in amino acids in peptides were
      mainly quantitative. After alcoholic fermentation, each medium was inoculated
      with Oenococcus oeni. Malolactic fermentation in the medium with the Deltapep4
      strain took 10 days longer than the control. This difference may have been due to
      a difference in the nitrogen composition of the two media. Free amino acids and
      amino acids in peptides were poorly consumed by O. oeni. Thus, the qualitative
      aspects of nitrogen composition, which depend in part on yeast metabolism, may be
      a determinant for the optimal growth of O. oeni in wine.

PMID- 16978355
TI  - Role of two 2-oxoglutarate:ferredoxin oxidoreductases in Hydrogenobacter
      thermophilus under aerobic and anaerobic conditions.
AB  - Hydrogenobacter thermophilus TK-6 is a thermophilic, hydrogen-oxidizing bacterium
      that fixes carbon dioxide as a sole carbon source via the reductive tricarboxylic
      acid cycle. 2-Oxoglutarate:ferredoxin oxidoreductase (OGOR) is one of the key
      enzymes in the pathway. Strain TK-6 has at least two isozymes of OGOR, namely For
      and Kor. These OGORs showed different expression patterns under aerobic
      conditions than under anaerobic conditions. In this work, we developed a
      homologous recombination method for Hydrogenobacter, and constructed a For mutant
      and a Kor mutant. Observation of phenotypes of the mutant strains showed that Kor
      was essential for anaerobic growth and that For activity supported robust aerobic
      growth of the organism.

PMID- 16978356
TI  - A new species of Pythium isolated from a vineyard in France.
AB  - Pythium apiculatum sp. nov. is a new oomycete characterized by the presence of
      both ornamented and smooth-walled oogonia. The ornamentations are blunt, and at
      times, bent. The oomycete was isolated from soil samples taken in a vineyard in
      the Burgundian region of France. Morphologically, it resembles some species
      having ornamented oogonia like Pythium radiosum, Pythium echinulatum, and
      resembles, also the species having smooth-walled oogonia like Pythium hypogynum
      and Pythium acrogynum. However, the oomycete has its own distinguishing
      characteristics which, when combined with molecular features, enables us to
      describe it as a new species. The taxonomic description of this new oomycete, its
      comparison with related species, and the sequence of the ITS region of its rRNA
      gene, are described in this article.

PMID- 16978357
TI  - Abundant presence of the gamma-like Proteobacterial pufM gene in oxic seawater.
AB  - Known anoxygenic photosynthetic bacteria (APB) affiliated to Gammaproteobacteria
      usually use anaerobic metabolism and are restricted to oxygen-free habitats.
      Here, we report abundant (average of 34.5%) presence of diverse APB related to
      gamma-like Proteobacteria in oxic oceanic surface water as indicated by the pufM
      gene, that encodes the M subunit of the light reaction centre complex. Thus, our
      sequences were most likely derived from aerobic anoxygenic phototrophs (AAnP).
      Two genetically distinct genotypes were revealed: one was from the oligotrophic
      North Pacific Ocean Gyre and the other, was from the trophic East China Sea and
      Bering Sea. The discovery of abundant presence of novel gamma-like
      Proteobacterial pufM gene in the oxic seawater extends the functional ecotypes of
      AAnP.

PMID- 16978358
TI  - Cloning of multiple cellulase cDNAs from Volvariella volvacea and their
      differential expression during substrate colonization and fruiting.
AB  - We used PCR-based methods to clone and sequence four previously unidentified
      cellulase cDNAs: cbhI-I, cbhI-II, cbhII-I and egII. CbhI-I, cbhI-II and cbhII-I
      consist of 1710, 1610 and 1453 bp, respectively, and encode for 512, 458 and 442
      amino acids, respectively. EgII consists of 1180 bp encoding for 310 amino acids,
      and belongs to family 61 of the glycosyl hydrolases. CbhI-I, cbhII-I and egII all
      have a modular structure, with the catalytic domain (CD) and cellulose-binding
      domain (CBD) located at the C-terminus in cbhI-I and egII, and at the N-terminus
      in cbhII-I. CbhI-II shows high homology to cbhI-I but lacks a CBD. Northern
      blotting revealed that cbhI-I, cbhI-II and cbhII-I were coordinately expressed at
      various stages of the mushroom developmental cycle (substrate colonization to
      mature fruit body), although the number of cbhI-I transcripts was much smaller.
      No egII expression was detectable during the substrate colonization phase but
      transcription levels increased as fruit body morphogenesis progressed.

PMID- 16978359
TI  - Molecular origin of two polysaccharides of Campylobacter jejuni 81116.
AB  - The nature of the polysaccharide molecules of the human enteric pathogen
      Campylobacter jejuni has been the subject of debate. Previously, C. jejuni 81116
      was shown to contain two different polysaccharides, one acidic (polysaccharide A)
      and the other neutral (polysaccharide B), occurring in a 3 : 1 ratio,
      respectively. The aim of this study was to determine the molecular origin of
      these polysaccharides. Using a combination of centrifugation, gel permeation
      chromatography, chemical assays, and (1)H-NMR analysis, polysaccharide B was
      shown to be derived from lipopolysaccharide and polysaccharide A from capsular
      polysaccharide. Thus, C. jejuni 81116 produces both lipopolysaccharide-like
      molecules and capsular polysaccharide.

PMID- 16978360
TI  - Functional characterization of the competence protein DprA/Smf in Escherichia
      coli.
AB  - In several bacterial species that show natural transformation, dprA has been
      described as a competence gene. The DprA protein has been suggested to be
      involved in the protection of incoming DNA. However, members of the dprA gene
      family (also called smf) can be detected in virtually all bacterial species,
      which suggests that their gene products have a more general function. We examined
      the function of the DprA/Smf homologue of Escherichia coli. Escherichia coli
      dprA/smf is able to partially restore transformation in a Haemophilus influenzae
      dprA mutant, which shows that dprA/smf genes from competent and noncompetent
      species are interchangeable with respect to their involvement in natural
      transformation. From this, we conclude that natural transformation is probably an
      additional function of these genes. Subsequently, the dprA/smf gene was deleted
      in various recombination mutants of E. coli, and the resultant phenotype was
      tested. All the resultant E. coli dprA/smf mutants did not differ from their
      parent strains with respect to transformation, Hfr-conjugation, recombination and
      DNA repair. Therefore, a role of DprA/Smf in DNA recombination could not be
      established and the basic function of dprA/smf remains unclear.

PMID- 16978361
TI  - Biochemical and functional characterization of triosephosphate isomerase from
      Mycobacterium tuberculosis H37Rv.
AB  - Triosephosphate isomerase (TPI), one of the key enzymes of the glycolytic
      pathway, is an attractive drug target against Mycobacterium tuberculosis as
      glycolysis provides the majority of the organism's energy requirements inside
      macrophages. To carry out biochemical and biophysical characterization, purified
      recombinant M. tuberculosis TPI produced in Escherichia coli was used. Mass
      spectrum analysis showed M. tuberculosis rTPI to be of 28 213 Da. The
      biologically active enzyme is a homodimer as determined by gel filtration
      chromatography. The M. tuberculosis TPI had a pH optimum in the range of 6-8 and
      a temperature optimum around 37 degrees C. Circular dichroism spectra analysis
      revealed that loss of secondary structure of rTPI occurs around 60 degrees C.
      Metal cations were not required for M. tuberculosis TPI activity. The k(cat) was
      4.1 x 10(6) min(-1). Importantly, the apparent K(m) value of M. tuberculosis rTPI
      for the substrate glyceraldehyde-3-phosphate is 84 microM which is sevenfold
      higher than the value reported for human TPI. The difference in K(m) is
      indicative of the difference in the active site of the human and M. tuberculosis
      TPI, which can be exploited for drug designing specifically targeting M.
      tuberculosis TPI.

PMID- 16978362
TI  - Molecular serotype identification of Streptococcus agalactiae of bovine origin by
      multiplex PCR-based reverse line blot (mPCR/RLB) hybridization assay.
AB  - We used a multiplex PCR-based reverse line blot (mPCR/RLB) hybridization assay
      and sequencing of a variable region of the cps cluster to identify serotypes of
      140 Streptococcus agalactiae (group B Streptococcus; GBS) isolates from cattle.
      Only 71 (51%) isolates were typeable using antisera, but molecular serotypes (MS)
      were assigned to 133 (95%) and 139 (99%) isolates by partial cpsE-cpsF-cpsG
      sequencing and mPCR/RLB, respectively. Ninety-four isolates (67%) belonged to MS
      III and most belonged to a molecular serosubtype (msst) III-3, which is uncommon
      among GBS isolates from humans. Our results demonstrate that cps clusters of
      bovine GBS differ significantly from those of GBS isolates from humans.

PMID- 16978363
TI  - Development of an ex vivo organ culture model using human gastro-intestinal
      tissue and Campylobacter jejuni.
AB  - Campylobacter jejuni is an important food-borne pathogen. However, relatively
      little is understood regarding its pathogenesis, and research is hampered by the
      lack of a suitable model. Recently, a number of groups have developed assays to
      study the pathogenic mechanisms of C. jejuni using cell culture models. Here, we
      report the development of an ex vivo organ culture model, allowing for the
      maintenance of intestinal mucosal tissue, to permit more complex host-bacterium
      interactions to be studied. Ex vivo organ culture highlights the propensity for
      C. jejuni to adhere to mucosal tissue via the flagellum, either as discrete
      colonies or as multicellular units.

PMID- 16978364
TI  - Characterization of a symbiotically defective serine auxotroph of Mesorhizobium
      ciceri.
AB  - A Tn5-induced mutant strain (TL68) of Mesorhizobium ciceri unable to grow with
      ammonium as the sole nitrogen source was isolated and characterized. Unlike its
      wild-type parent (strain TAL620), the mutant had an absolute dependence on serine
      to grow. Cloning of the DNA region containing Tn5 and sequence analysis showed
      that Tn5 was inserted into the gene coding for 3-phosphoglycerate dehydrogenase,
      which catalyses the first step in the serine biosynthetic pathway. The role of
      serine biosynthesis of M. ciceri in the establishment of nitrogen-fixing
      symbiosis with chickpea (Cicer arietinum L) was investigated using the mutant
      TL68. The serA(-) mutant (TL68) was unable to elicit the development of efficient
      nodules on the roots of Cicer arietinum L. The addition of serine to the plant
      growth medium restored the ability of the mutant to nodulate Cicer arietinum, and
      the nodules were able to fix nitrogen.

PMID- 16978365
TI  - Loss of O-antigen increases cell shape abnormalities in penicillin-binding
      protein mutants of Escherichia coli.
AB  - Escherichia coli mutants lacking multiple penicillin-binding proteins (PBPs)
      produce aberrantly shaped cells. However, most of these experiments have been
      performed in E. coli K12 strains, which do not attach a complete O-antigen to
      their outer membrane lipopolysaccharide. We constructed mutants in different
      genetic backgrounds and found that the frequency of morphological deformities was
      higher in strains lacking the O-antigen. Also, complementing O-negative mutants
      with a heterologous O-antigen from Klebsiella returned a substantial fraction of
      misshapen cells to a normal morphology. Thus, the O-antigen contributes to cell
      shape in E. coli, perhaps by reducing the number of ectopic poles, which may be
      the proximal cause of shape abnormalities.

PMID- 16978366
TI  - Time to move from serum creatinine to eGFR.

PMID- 16978367
TI  - Effects of oral magnesium supplementation on glycaemic control in Type 2
      diabetes: a meta-analysis of randomized double-blind controlled trials.
AB  - AIMS: The aim of this study was to assess the evidence on the effect of oral
      magnesium supplementation on glycaemic control in patients with Type 2 diabetes.
      METHODS: We searched the electronic databases of medline, embase and the Cochrane
      Controlled Trials Register up to January 2005. We identified nine randomized
      double-blind controlled trials with a total of 370 patients with Type 2 diabetes
      and of duration 4-16 weeks. The median dose of oral magnesium supplementation was
      15 mmol/day (360 mg/day) in the treatment groups. The primary outcome was
      glycaemic control, as measured by glycated haemoglobin (HbA(1c)) or fasting blood
      glucose levels; the secondary outcomes included body mass index, blood pressure
      (BP) and lipids. Using a random-effects model, we calculated the weighted mean
      differences (WMD) and 95% confidence interval (CI). RESULTS: After a median
      duration of 12 weeks, the weighted mean post-intervention fasting glucose was
      significantly lower in the treatment groups compared with the placebo groups [
      0.56 mmol/l (95% CI, -1.10 to -0.01); P for heterogeneity = 0.02]. The difference
      in post-intervention HbA(1c) between magnesium supplementation groups and control
      groups was not significant [-0.31% (95% CI, -0.81 to 0.19); P for heterogeneity =
      0.10]. Neither systolic nor diastolic BP was significantly changed. Magnesium
      supplementation increased on high-density lipoprotein (HDL) cholesterol levels
      [0.08 mmol/l (95% CI, 0.03 to 0.14); P for heterogeneity = 0.36] but had no
      effect on total cholesterol, low-density lipoprotein (LDL) cholesterol and
      triglyceride. CONCLUSIONS: Oral magnesium supplementation for 4-16 weeks may be
      effective in reducing plasma fasting glucose levels and raising HDL cholesterol
      in patients with Type 2 diabetes, although the long-term benefits and safety of
      magnesium treatment on glycaemic control remain to be determined.

PMID- 16978368
TI  - Clinical utility of estimated glomerular filtration rates in predicting renal
      risk in a district diabetes population.
AB  - AIMS: To determine the utility of estimated glomerular filtration rates (eGFR) in
      predicting renal risk over and above currently available strategies that
      incorporate serum creatinine and microalbuminuria in a diabetes population.
      METHODS: Cross-sectional study of 4548 diabetic individuals attending a single
      centre over an 18-month period. Glomerular filtration rates were estimated using
      the Modification of Diet in Renal Disease (MDRD) equation. Microalbuminuria was
      measured using spot morning urine for albumin:creatinine ratio (ACR). SPSS was
      utilized for statistical analysis. RESULTS: Of the 4303 subjects with complete
      data, 373 (9%), 2634 (61%), 1197 (28%) and 99 (2%) individuals, respectively, had
      eGFR > 90, 90-60, 60-30 and < 30 ml/min per 1.73 m(2), respectively. Of those
      with clinically meaningful renal disease (eGFR < 60 ml/min per 1.73 m(2)), only
      42% and 45%, respectively, were identified as at risk by clinical strategies
      utilizing serum creatinine and urine ACR individually. Even using the two
      together, 38% of the patients at risk would still not have been identified, since
      they had normal values of both. CONCLUSION: Current strategies utilizing serum
      creatinine and urine ACR are insufficient for the detection of renal disease in
      diabetes. Clinicians should consider monitoring GFR estimates in addition to
      assessing blood pressure, serum creatinine and urine albumin excretion in order
      to assess renal status and risk in adults with diabetes.

PMID- 16978369
TI  - Short-term suppression of plasma free fatty acids fails to improve insulin
      sensitivity when intramyocellular lipid is elevated.
AB  - AIMS: Metabolic responses to manipulation of the plasma free fatty acid (FFA)
      concentration were assessed in six healthy men via cross-over design to determine
      whether FFAs independently influence insulin sensitivity. METHODS:
      Intramyocellular lipid (IMCL) was measured by proton magnetic resonance
      spectroscopy and insulin sensitivity via frequently sampled intravenous glucose
      tolerance test (IVGTT) after 67 h of two identical low carbohydrate/high fat (LC)
      diets which were used to elevate IMCL and plasma FFAs. To uncouple the influence
      of FFAs and IMCL on insulin sensitivity, FFAs were suppressed 30 min prior to and
      during IVGTT in one treatment [LC + nicotinic acid (NA)] by NA ingestion.
      RESULTS: Vastus lateralis IMCL was significantly elevated in LC (13.3 +/- 1.1 x
      10(-3)) and LC + NA (13.5 +/- 1.1 x 10(-3)) (P < 0.01 for both), but was not
      different between conditions (P > 0.05). Plasma FFAs were raised in LC (0.79 +/-
      0.08 mmol/l) and LC + NA (0.80 +/- 0.11 mmol/l) (P < 0.01 for both) and were
      significantly reduced by NA ingestion prior to (0.36 +/- 0.05 mmol/l, P < 0.01)
      and during IVGTT (P < 0.05) in LC + NA. Despite marked differences in plasma FFA
      availability, insulin sensitivity and glucose tolerance were not different
      between LC and LC + NA (P > 0.05 for both). CONCLUSIONS: Plasma FFAs appear to
      exert no immediate effect on insulin sensitivity/glucose tolerance independent of
      their action on intracellular lipid moieties. Further research is required to
      elucidate the duration of FFA suppression required to restore insulin sensitivity
      following lipid-induced insulin resistance.

PMID- 16978370
TI  - Effect of metformin plus roziglitazone compared with metformin alone on glycaemic
      control in well-controlled Type 2 diabetes.
AB  - AIMS: To investigate the effect of metformin plus roziglitazione (RSGMET)
      compared with metformin alone (MET) on glycaemic control in well-controlled Type
      2 diabetes. METHODS: Subjects (drug naive or those on glucose-lowering
      monotherapy) were randomized (n = 526), following a 4-week placebo run-in period,
      to RSGMET [4 mg rosiglitazone (RSG)/500 mg MET] or MET 500 mg. From weeks 2-18,
      medication was escalated every 4 weeks (based on gastrointestinal tolerability),
      then remained at RSGMET 8 mg/2 g or MET 3 g for 14 weeks. RESULTS: RSGMET reduced
      HbA(1c) from 7.2 +/- 0.6 to 6.7 +/- 0.8% at week 32, compared with a reduction
      from 7.2 +/- 0.6 to 6.8 +/- 0.9% with MET (treatment difference -0.13%; P =
      0.0357). More subjects achieved an HbA(1c) value of </= 6.5% at week 32 with
      RSGMET (51.6 vs. 43.7%), but the treatment difference was not significant (odds
      ratio 1.37, P = 0.0949). RSGMET produced larger reductions from baseline in mean
      fasting plasma glucose (adjusted difference -0.62 mmol/l, P < 0.0001), with the
      odds ratio of achieving a target of < 7.0 mmol/l being 2.33 (P < 0.0001).
      Statistically significant differences in favour of RSGMET relative to MET were
      seen for homeostatic model assessment (HOMA)-derived estimates of insulin
      sensitivity and pancreatic B-cell function, C-reactive protein (CRP), and
      systolic blood pressure. Overall rates of gastrointestinal adverse events
      (relevant to the known profile of MET) were comparable, but with a lower
      incidence of diarrhoea (8 vs. 18%) with RSGMET. Hypoglycaemia was reported in </=
      7% subjects per group. CONCLUSIONS: RSGMET provided similar short-term glycaemic
      control to MET with greater improvements in estimates of insulin sensitivity, B
      cell function and CRP, with less diarrhoea and low risk of biochemical
      hypoglycaemia, suggesting that early use of combination therapy may be
      appropriate.

PMID- 16978371
TI  - The effect of metformin on blood glucose control in overweight patients with Type
      1 diabetes.
AB  - AIMS: In a randomized, double-blind, cross-over study, we investigated the effect
      of metformin on blood glucose control and daily insulin dose in overweight
      patients with Type 1 diabetes. METHODS: We studied 15 C-peptide-negative
      patients, aged 48 +/- 12 years, with a body mass index of 31.3 +/- 2.6 kg/m(2).
      Each patient had a 'screening visit', followed by a 4-week 'run-in' period. This
      was followed by two separate 16-week 'study' (treatment) periods, separated by a
      4-week 'wash-out' period. Patients received either metformin or placebo during
      the 'study' periods, in random order. RESULTS: HbA(1c) was significantly lower
      following 16 weeks of treatment with metformin (7.8 +/- 1.1%) compared with
      baseline (8.5 +/- 1.4%; P < 0.005) and placebo (8.6 +/- 1.2%; P < 0.005). Fasting
      plasma glucose, following 16 weeks of metformin treatment, was significantly
      lower (8.3 +/- 2.8 mmol/l) compared with baseline (12.4 +/- 3.0 mmol/l; P < 0.01)
      and placebo (12.6 +/- 3.4 mmol/l; P < 0.01). Compared with baseline (60 +/- 14
      units), total daily insulin dose was significantly lower following the addition
      of metformin (50 +/- 13 units; P < 0.05) and this final total daily insulin dose
      in the metformin group was lower compared with placebo (58 +/- 12 units, P <
      0.05). Body weight did not change following metformin or placebo treatment.
      CONCLUSION: Metformin can effectively improve glycaemic control and reduce the
      total daily insulin dose in overweight people with Type 1 diabetes.

PMID- 16978372
TI  - The Gly482Ser variant of the PPARGC1 gene is associated with Type 2 diabetes
      mellitus in northern Chinese, especially men.
AB  - AIMS: To investigate the prevalence of the Gly482Ser polymorphism of the PPARGC1
      gene in a northern Chinese population and to clarify the susceptibility of
      individuals with the Gly482Ser polymorphism to insulin resistance and related
      diseases. METHODS: We studied the association of the Gly482Ser polymorphism
      identified in the PPARGC1 gene with Type 2 diabetes mellitus (T2DM) in 390
      unrelated patients with T2DM and 525 control subjects with normal glucose
      tolerance. Clinical parameters and measures of insulin resistance were recorded.
      Genotypes were determined by the polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) method, which was further confirmed by direct
      sequencing in 20 randomly selected cases. RESULTS: The Gly482Ser polymorphism was
      common in the northern Chinese population. Univariate analysis indicated no
      statistically significant differences in allele frequencies or genotype
      frequencies of the Gly482Ser polymorphism in diabetic and control subjects (minor
      482Ser allele frequency 44.4 vs. 41.4%, P = 0.169). However, logistic regression
      analysis demonstrated a positive 1.645-fold higher risk of the Ser/Ser genotype
      for T2DM (P = 0.039, 95% CI = 1.026-2.632). After stratification by gender, the
      risk of Type 2 diabetes in men was increased 1.852-fold (95% CI = 1.125-3.049) in
      those with the Ser/X genotype compared with those with the Gly/Gly genotype (P =
      0.015). No associations were observed between the Gly482Ser polymorphism and
      parameters of insulin resistance, obesity and hypertension. CONCLUSION: The
      Gly482Ser variant of the PPARGC1 gene might contribute to susceptibility to T2DM
      in northern Chinese subjects. The Ser/X genotype of the Gly482Ser polymorphism in
      the PPARGC1 gene appears to be a risk factor for T2DM in northern Chinese men.

PMID- 16978374
TI  - Characterization and comparison of health-related utility in people with diabetes
      with various single and multiple vascular complications.
AB  - AIMS: To characterize and compare health-related utility in a large cohort of
      patients treated in hospital with diabetes and with single and multiple
      comorbidities. METHODS: The study was conducted in Cardiff and the Vale of
      Glamorgan, UK. Health-related utility was measured using the EQ5D(index), a
      standardized instrument for measuring health outcome. Patients from the Health
      Outcomes Data Repository (HODaR) were surveyed by postal questionnaire 6 weeks
      post discharge for in-patients and during clinics for patients attending as out
      patients between January 2002 and July 2005. Patients with diabetes were
      identified by a previous history of in-patient admission with diabetes or as an
      out-patient with diabetes recorded as a coexisting diagnosis. RESULTS: We
      identified 4502 patients with diabetes. Mean ages were 65.4 and 64.2 years for
      males and females, respectively. Of these, 2003 (45%) had no recorded vascular
      complication. Overall, the EQ5D(index) was 0.584 (sd 0.325) for males and 0.533
      (sd 0.351) for females. For those without any vascular complications the mean
      EQ5D(index) was 0.735 (sd 0.288). In a general linear model, the presence of
      single and multiple complications had a detrimental impact on the EQ5D(index).
      CONCLUSION: The results of this study provide an indication of the true impact of
      diabetes in terms of health-related utility. There was a decrease in the mean
      EQ5D(index) for those with vascular complications. Economic models of diabetes
      that have used additive or multiplicative methods to assess utility in
      individuals with several complications may be unreliable, and direct
      measurements, such as this, are recommended.

PMID- 16978373
TI  - Genetic influences of the intercellular adhesion molecule 1 (ICAM-1) gene
      polymorphisms in development of Type 1 diabetes and diabetic nephropathy.
AB  - AIM: The intercellular adhesion molecule-1 (ICAM-1) gene is located on chromosome
      19p13, which is linked to Type 1 diabetes (T1D). ICAM-1 expression is related to
      development of T1D and diabetic nephropathy. The present study aims to evaluate
      the genetic influence of ICAM-1 gene polymorphisms on the development of T1D and
      diabetic nephropathy. METHODS: Five valid single nucleotide polymorphisms (SNPs)
      were genotyped in 432 T1D patients (196 patients had diabetic nephropathy) and
      187 non-diabetic control subjects by using dynamic allele-specific hybridization
      (DASH) and pyrosequencing. RESULTS: SNPs rs281432(C/G) and rs5498 E469K(A/G) had
      high heterozygous indexes. They were significantly associated with T1D [P =
      0.026, OR = 1.644 (95% CI 1.138-2.376) and P < 0.001, OR = 2.456 (1.588-3.8)].
      Frequencies of the C allele in SNP rs281432(C/G) and the A allele in SNP rs5498
      E469K(A/G) increased stepwise from non-diabetic control subjects to T1D patients
      without diabetic nephropathy and T1D patients with diabetic nephropathy. Further
      analysis for these two SNPs indicated that T1D patients had increased frequency
      of the common haplotype C-A, in comparison with non-diabetic control subjects
      (38.1 vs. 32.1%, P = 0.035). CONCLUSION: The present study provided evidence that
      SNPs rs281432(C/G) and rs5498 E469K(A/G) in the ICAM-1 gene confer susceptibility
      to the development of T1D and might also be associated with diabetic nephropathy
      in Swedish Caucasians.

PMID- 16978376
TI  - Psychological morbidity and problems of daily living in people with visual loss
      and diabetes: do they differ from people without diabetes?
AB  - AIMS: To examine psychological adjustment and changes in the activities of daily
      living in relation to visual loss in diabetes. METHODS: This was an incident
      cohort, longitudinal, observational study contrasting the adjustment of
      individuals with visual loss associated with diabetes and those whose visual loss
      arose from other conditions; in the year subsequent to registration for blindness
      and 12 months later, 124 individuals participated in the study (51 with diabetes
      and 73 without). Participants provided demographic and biomedical information,
      and completed the Brief COPE, Hospital Anxiety and Depression Scale, SF-36,
      Instrumental Activities of Daily Living scale and Social Avoidance and Distress
      Scale via interview. People with diabetes were compared with those without.
      RESULTS: Both diabetic and non-diabetic groups showed elevated and comparable
      levels of psychological morbidity, sustained over time. Significant differences
      in functional adjustment were found at initial interview: people with diabetes
      having more problems coping but these were no longer present 1 year later.
      CONCLUSIONS: There was a significant and enduring elevation of anxiety and
      depression in those who were newly registered blind or visually handicapped.
      Taking these findings into account, psychological assessment should be developed
      for all those experiencing visual loss.

PMID- 16978375
TI  - Perception of, and anxiety levels induced by, laser treatment in patients with
      sight-threatening diabetic retinopathy. A multicentre study.
AB  - AIMS: To investigate how laser treatment is perceived, in terms of anxiety and
      awareness, by diabetic patients attending four centres in Northern Italy with
      specific interest and expertise in diabetic retinopathy, where work settings and
      flow are organized differently. METHODS: The Hospital Anxiety and Depression
      Scale (HADS), Family Apgar-List of Threatening Experiences (FA-LTE), State-Trait
      Anxiety Inventories 1 and 2 (STAI-1 and STAI-2) questionnaires were completed by
      259 patients, 131 waiting for laser treatment and 128 control subejcts awaiting
      non-intervention visits. Open questions were also asked on whether patients had
      ever heard the word 'laser' and whether they could describe laser treatment.
      RESULTS: High scores were detected by HADS, STAI-1 and STAI-2 among patients
      waiting for photocoagulation. Anxiety was greater in women and people with poor
      schooling. After controlling for centres, gender, previous laser treatment and
      schooling, HADS and STAI-1 remained significantly lower among persons waiting for
      non-intervention visits. Having received photocoagulation previously did not
      modify anxiety. Anxiety was lower in those centres where facilities and resources
      were more patient-oriented. Most patients could neither describe photocoagulation
      nor explain why they were about to receive it, but had a negative perception and
      some described it with words evoking cruelty and pain. CONCLUSIONS: These data
      suggest that laser treatment is experienced as an event that causes anxiety.
      Preoperative education and counselling may help to reduce fear and patients'
      avoidance of treatment.

PMID- 16978377
TI  - Use of vascular risk-modifying medications for diabetic patients differs between
      physician specialties.
AB  - AIMS: Although heart disease and stroke are the underlying causes of death in
      most people with diabetes, vascular risk modification targets are frequently not
      met. This study examined whether vascular risk-modifying medication utilization
      for diabetic patients differed among physician specialties. METHODS: A population
      based study using administrative data from 105 715 people aged >/= 65 years with
      newly diagnosed diabetes in Ontario between 1994 and 2001. The receipt of
      antihypertensive and lipid-lowering drugs was compared between patients who had
      regular care from endocrinologists, internists/geriatricians and family
      physicians. Hierarchical logistic regression adjusted for patient-level
      differences, physician-level differences and patient clustering within
      physicians. RESULTS: Only two-thirds of patients received antihypertensive drugs
      and about one-quarter received lipid-lowering drugs. Compared with patients of
      family physicians, the adjusted odds ratios for antihypertensive drug use were
      1.27 [95% confidence interval (CI) 1.16, 1.38] for patients of
      internists/geriatricians and 1.03 (95% CI 0.94, 1.12) for patients of
      endocrinologists. For lipid-lowering drugs, the odds ratios were 1.20 (95% CI
      1.11, 1.30) for patients of internists/geriatricians and 1.58 (95% CI 1.42, 1.76)
      for patients of endocrinologists. CONCLUSIONS: Despite recommendations to use
      vascular risk-modifying medication for most older people with diabetes, many
      patients were not receiving these medications. Medication utilization differed
      between physician specialties, with family physicians having the lowest rates of
      use. Notably, although blood pressure control has the greatest evidence of
      benefit and is cost-saving, endocrinologists did not use antihypertensive drugs
      more often than family physicians after adjustment for other differences.

PMID- 16978378
TI  - Performance of the continuous glucose monitoring system (CGMS) during development
      of ketosis in patients on insulin pump therapy.
AB  - AIMS: Ketoacidosis is one of the most severe complications of Type 1 diabetes.
      Development of ketosis leads to substantial shifts in electrolyte and ion
      concentrations in the different fluid compartments of the body. This study was
      performed to investigate the performance of the continuous glucose monitoring
      device (CGMS) during ketoacidosis. METHODS: Twelve patients with Type 1 diabetes
      using continuous subcutaneous insulin infusion (CSII) participated in this trial
      [10 women, two men; age (mean +/- sd) 34 +/- 9 years; disease duration 17 +/- 10
      years; HbA(1c) 7.1 +/- 1.0%]. In the morning, patients ate breakfast and the
      insulin pump was stopped at 11.00 h and restarted after 8 h. Observation
      parameters during this experiment were: blood glucose (laboratory reference and
      CGMS), 3-hydroxy-butyrate (3-OHB), pH, Na, pCO(2), pO(2), free fatty acids,
      osmolarity, standard bicarbonate, and lactate. RESULTS: Blood glucose increased
      and reached a plateau within 2 h after pump stop (from 6.2 +/- 2.56 to 16.7 +/-
      4.44 mmol/l, P < 0.001). A constant increase in 3-OHB (from 0.0 to 0.8 +/- 0.5
      mmol/l, P < 0.001) and decrease in pH (from 7.43 +/- 0.02 to 7.40 +/- 0.03, P <
      0.05) indicated ketosis development. Na decreased from 141 +/- 1.4 to 138 +/- 2.8
      mmol/l, P < 0.001). Free fatty acids increased from 0.577 +/- 0.330 to 1.330 +/-
      0.462 mmol/l (P < 0.001). The CGMS values showed excellent agreement with the
      capillary blood laboratory method during the entire experiment, and a modified
      error grid analysis revealed that 99.5% of the values were in the clinically
      acceptable zones A and B. CONCLUSION: The CGMS device was confirmed to be
      reliable and accurate during the development of hyperglycaemia and ketotic
      conditions.

PMID- 16978379
TI  - The prevalence of hypertension and diabetes defined by fasting and 2-h plasma
      glucose criteria in urban Nepal.
AB  - AIMS: To determine the prevalence of diabetes, impaired fasting glucose and
      impaired glucose tolerance (IGT) in people aged >/= 40 years in urban communities
      of Nepal, comparing the fasting and 2-h plasma glucose (PG) criteria for
      diagnosis of diabetes and to relate the prevalence to age, gender and
      hypertension. METHODS: Field surveys of fasting and 2-h PG and blood pressure
      (BP) were done by cluster sampling in seven urban populations of Nepal. Of 1180
      eligible individuals invited, 1012 (85.7%) aged >/= 40 years participated.
      RESULT: The age and sex standardized prevalence of diabetes (known and newly
      diagnosed), IGT and impaired fasting glycaemia (IFG) were 19.0%, 10.6% and 9.9%,
      respectively. Of the total population, 30.5% (37.8% of men and 25.3% of women)
      had some abnormality of glucose tolerance. Of all diabetic individuals, 54.4%
      (53.8% of men and 55.1% of women) were undiagnosed. The prevalence of diabetes
      increased with age until the age of 75 years. The prevalence of diabetes was
      higher in men than in women (P < 0.001). The sensitivity of the fasting plasma
      glucose (FPG) criterion compared with either FPG or 2-h PG or both criteria for
      the diagnosis of diabetes was 70.5%[95% confidence interval (CI) 60.7, 78.8] and
      the corresponding sensitivity of 2-h PG criterion was 79% (95% CI 69.8, 86.1).
      The age- and sex-standardized prevalence of hypertension (BP >/= 140/90 mmHg) was
      22.7%. Hypertension was less common in subjects with normal plasma glucose than
      in those with diabetes (18.8% vs. 36.7%). Similarly, of all subjects with
      hypertension, 29.1% had diabetes (known or newly diagnosed) and 43.0% had glucose
      intolerance of some form. CONCLUSIONS: Our study shows that diabetes and
      hypertension are common and related problems in people aged >/= 40 years in urban
      Nepal. The overall sensitivity of the 2-h PG criteria was greater than that of
      the FPG criteria for diagnosing diabetes, except in subjects aged >/= 60 years.

PMID- 16978380
TI  - Early onset insulin-dependent diabetes mellitus as an initial manifestation of
      aceruloplasminaemia.
AB  - BACKGROUND: Aceruloplasminaemia is an autosomal recessive disorder caused by
      specific mutations in the ceruloplasmin gene. Aceruloplasminaemia is clinically
      characterized by diabetes mellitus, pigment degeneration of the retina, and
      neurological abnormalities, such as cerebellar ataxia, extrapyramidal signs, and
      dementia. We present a patient with aceruloplasminaemia who, until progressive
      neurological abnormalities were noticed, had been treated for more than 30 years
      as having Type 1 diabetes mellitus requiring multiple insulin injection therapy.
      CASE REPORT: The patient was a 58-year-old man. At the age of 23 years, he
      developed diabetes that required multiple insulin injection therapy. At the age
      of 39 years, he was commenced on continuous subcutaneous insulin infusion (CSII)
      therapy. Despite CSII therapy, the patient's blood glucose levels were poorly
      controlled (HbA(1c), approximately 9.5%). He was diagnosed as having
      aceruloplasminaemia at 58 years of age when he presented with progressive
      cerebellar ataxia, extrapyramidal signs of recent onset and pigment degeneration
      of the retina. CONCLUSIONS: It is possible that some diabetic patients with
      aceruloplasminaemia are mistakenly diagnosed as having Type 1 diabetes mellitus,
      as they have reduced insulin secretion and develop diabetes at a younger age,
      before neurological abnormalities associated with aceruloplasminaemia are
      apparent. Therefore, aceruloplasminaemia should be considered in patients with
      insulin-dependent diabetes mellitus who develop progressive neurological
      abnormalities of unknown aetiology along with a microcytic hypochromic anaemia
      and retinal degeneration.

PMID- 16978381
TI  - Large-scale study of the -232C > G polymorphism of PCK1 in Type 2 diabetes.
AB  - AIMS: Phosphoenolpyruvate carboxykinase (PEPCK) is a catalyst of the rate
      limiting step in the gluconeogenic pathway and is regulated at the
      transcriptional level predominantly by insulin, glucocorticoids, glucagon, and
      cAMP. The -232C > G polymorphism in the gene encoding PEPCK (PCK1) is reported to
      associate with Type 2 diabetes in Canadian Caucasians and Oji-Cree populations.
      We have estimated the impact of the PCK1-232C > G polymorphism in a relatively
      large-scale case-control study of Type 2 diabetes and in association studies of
      common metabolic phenotypes. Interaction studies of the PCK1-232C > G
      polymorphism with variants in the genes encoding peroxisome proliferator
      activated receptor-gamma co-activator (PGC)-1alpha and hepatic nuclear factor
      (HNF)-4alpha were also performed. METHODS: PCK1-232C > G was genotyped in a total
      of 7467 Danish white subjects using TaqMan allelic discrimination. A case-control
      study of Type 2 diabetes was performed using 6057 of the participants, and
      quantitative trait studies of metabolic variables were carried out in a subgroup
      of 5718 non-diabetic subjects. Additionally, variants in PGC-1alpha (Gly482Ser)
      and HNF-4alpha (Thr130Ile, Val255Met, and rs1884614) were investigated for
      epistatic interaction with the PCK1-232C > G polymorphism. RESULTS: In the case
      control study of Type 2 diabetes of 1377 Type 2 diabetic patients and 4680
      normoglycaemic and normal glucose-tolerant subjects we found no association of
      the PCK1-232C > G polymorphism with diabetes. In addition, the variant was not
      associated with age of clinical onset of Type 2 diabetes. In the study of 5718
      non-diabetic subjects, we found no relationships of quantitative metabolic traits
      with the PCK1-232C > G polymorphism. We failed to demonstrate any convincing
      epistatic effects of the variants in the genes encoding PGC-1alpha and HNF-4alpha
      with the PCK1-232C > G polymorphism. CONCLUSIONS: The PCK1-232C > G polymorphism
      is not a major contributor to the pathogenesis of Type 2 diabetes in the Danish
      population.

PMID- 16978382
TI  - Phenotypic and genetic analyses of T-cell-mediated immunoregulation in patients
      with Type 1 diabetes.
AB  - AIMS: To investigate the contribution of regulatory T cells and co-stimulatory
      molecules in CD4(+) T cells to the development of Type 1 diabetes (T1D). METHODS:
      Twelve patients with T1D, nine patients with systemic lupus erythematosus (SLE),
      and 12 age-matched healthy control subjects participated. We analysed the
      proportions of CD25(+)CD4(+) T cells and natural killer T cells (NKT cells), and
      the expression levels of Foxp3, CTLA-4, CD28, ICOS, PD-1 and BTLA in peripheral
      blood mononuclear cells and purified CD4(+) T cells. RESULTS: There were no
      significant differences in the proportions of CD25(+) CD4(+) T cells or NKT cells
      among the three groups. PD-1 expression levels of peripheral CD4(+) T cells from
      T1D patients were significantly lower than those from healthy control subjects (P
      = 0.00066). In contrast, PD-1 expression levels were similar in SLE patients and
      healthy control subjects. The expression levels of Foxp3, CTLA-4, CD28, ICOS and
      BTLA were similar in the three groups. CONCLUSIONS: Decreased expression of the
      PD-1 gene in CD4(+) T cells may contribute to the development and/or maintenance
      of autoimmune T1D. As the population studied was small and heterogeneous, further
      studies are required to confirm the findings.

PMID- 16978383
TI  - A simple way to estimate mean plasma glucose and to identify Type 2 diabetic
      subjects with poor glycaemic control when a standardized HbA1c assay is not
      available.
AB  - AIMS: To evaluate the relationship between HbA(1c) and fasting plasma glucose
      (FPG) and postprandial plasma glucose (PPG) levels, and to estimate the mean
      plasma glucose (mPG) derived from FPG and PPG that would predict Type 2 diabetic
      subjects with poor glycaemic control. METHODS: FPG, PPG and HbA(1c) values from
      565 Type 2 diabetic patients (247 men and 318 women) were recorded. Linear
      regression analysis and Pearson's correlation was used to determine the
      relationship between HbA(1c), FPG and PPG. FPG and PPG were included as
      explanatory variables of HbA(1c) in linear regression analysis. RESULTS: The
      American Diabetes Association's objective of achieving an HbA(1c) level < 7.0%
      was obtained in 26.2% of the patients. The coefficients of FPG and PPG which
      determined HbA(1c) were similar. Therefore, mPG was calculated using the equation
      (FPG + PPG)/2. Pearson's correlation coefficient for HbA(1c) and FPG, PPG and mPG
      were 0.723 (P < 0.0001), 0.734 and 0.761 (P < 0.0001), respectively. A mPG cut
      off value of 10 mmol/l predicted an HbA(1c) > 7% in the whole population, with a
      sensitivity of 84.2% and specificity of 80.4%. The area was high (0.90) in
      receiver-operating characteristic (ROC) curve analysis performed to examine the
      performance of mPG to predict HbA(1c) > 7%. CONCLUSIONS: The mPG derived from FPG
      and PPG correlates strongly with HbA(1c). We therefore suggest that using a cut
      off of 10 mmol/l for mPG may be appropriate in diabetes management in the primary
      care setting, where most management of Type 2 diabetes occurs.

PMID- 16978384
TI  - Young adults with Type 1 diabetes in tertiary education: do students receive
      adequate specialist care?
AB  - AIMS: To examine the clinical characteristics of, and diabetes management
      provided for, young people with Type 1 diabetes in tertiary education. METHODS:
      The medical case records of a group of 55 students aged 18-24 years, all of whom
      had Type 1 diabetes and had been referred to a hospital diabetes clinic, were
      examined. RESULTS: A mean (SD) attendance of 80% (28%) was observed for all
      clinic appointments. Despite greater use of intensified insulin therapy
      (increasing from 37% to 83%) of students neither mean HbA1c nor mean body mass
      index changed significantly. Microvascular complications were infrequent.
      Documentation in the case notes of the frequency of home blood glucose monitoring
      was inadequate in 25% of patients as was the recorded frequency of mild (self
      treated) hypoglycaemia in (20%) of patients. CONCLUSIONS: Despite a satisfactory
      frequency of clinic attendance and organisation of insulin regimens by medical
      staff, glycaemic control remained unchanged throughout University attendance. The
      inadequate documentation of dietary habits, frequency of home blood glucose
      monitoring, hypoglycaemia, social habits and activities in both groups may
      provide a partial explanation, as other variables were not addressed. Young
      adults with Type 1 diabetes may benefit from receiving specialist care in a
      clinic dedicated to their particular needs.

PMID- 16978385
TI  - Plasminogen activator inhibitor-1 and the risk of Type 2 diabetes mellitus in
      American Indians: the Strong Heart Study.

PMID- 16978387
TI  - Treating insulin allergy with continuous subcutaneous insulin infusion (CSII).

PMID- 16978390
TI  - PEX genes in fungal genomes: common, rare or redundant.
AB  - PEX genes encode proteins, termed peroxins, that are required for the biogenesis
      and proliferation of microbodies (peroxisomes). We have screened the available
      protein and DNA databases to identify putative peroxin orthologs in 17 fungal
      species (yeast and filamentous fungi) and in humans. This analysis demonstrated
      that most peroxins are present in all fungi under study. Only Pex16p is absent in
      most yeast species, with the exception of Yarrowia lipolytica, but this peroxin
      is present in all filamentous fungi. Furthermore, we found that the Y. lipolytica
      PEX9 gene, a putative orphan gene, might encode a Pex26p ortholog. In addition,
      in the genomes of Saccharomyces cerevisiae and Candida glabrata, several PEX
      genes appear to have been duplicated, exemplified by the presence of paralogs of
      the peroxins Pex5p and Pex21p, which were absent in other organisms. In all
      organisms, we observed multiple paralogs of the peroxins involved in organelle
      proliferation. These proteins belong to two groups of peroxins that we propose to
      designate the Pex11p and Pex23p families. This redundancy may complicate future
      studies on peroxisome biogenesis and proliferation in fungal species.

PMID- 16978391
TI  - Formation and nuclear export of preribosomes are functionally linked to the small
      ubiquitin-related modifier pathway.
AB  - Ribosomal precursor particles are initially assembled in the nucleolus prior to
      their transfer to the nucleoplasm and export to the cytoplasm. In a screen to
      identify thermosensitive (ts) mutants defective in the export of pre-60S
      ribosomal subunit, we isolated the rix16-1 mutant. In this strain, nucleolar
      accumulation of the Rpl25-eGFP reporter was complemented by UBA2 (a subunit of
      the E1 sumoylation enzyme). Mutations in UBC9 (E2 enzyme), ULP1 [small-ubiquitin
      related modifier (SUMO) isopeptidase] and SMT3 (SUMO-1) caused 60S export
      defects. A directed analysis of the SUMO proteome revealed that many ribosome
      biogenesis factors are sumoylated. Importantly, preribosomal particles along both
      the 60S and the 40S synthesis pathways were decorated with SUMO, showing its
      direct involvement. Consistent with this, early 60S assembly factors were
      genetically linked to SUMO conjugation. Notably, the SUMO deconjugating enzyme
      Ulp1, which localizes to the nuclear pore complex (NPC), was functionally linked
      to the 60S export factor Mtr2. Together our data suggest that sumoylation of
      preribosomal particles in the nucleus and subsequent desumoylation at the NPC is
      necessary for efficient ribosome biogenesis and export in eukaryotes.

PMID- 16978392
TI  - Palmitoylation plays a role in targeting Vac8p to specific membrane subdomains.
AB  - Vac8p is a multifunctional yeast protein involved in several distinct vacuolar
      events including vacuole inheritance, vacuole homotypic fusion, nucleus-vacuole
      junction formation and the cytoplasm to vacuole protein targeting pathway. Vac8p
      associates with the vacuole membrane via myristoylation and palmitoylation. Vac8p
      has three putative palmitoylation sites, at Cys 4, 5 and 7. Here, we show that
      each of these cysteines may serve as a palmitoylation site. Palmitoylation at Cys
      7 alone provides partial function of Vac8p, whereas palmitoylation at either Cys
      4 or Cys 5 alone is sufficient for Vac8p function. In the former mutant, there is
      a severe defect in the localization of Vac8p to the vacuole membrane, while in
      the latter mutants, there is a partial defect in the localization of Vac8p. In
      addition, our studies provide evidence that palmitoylation targets Vac8p to
      specific membrane subdomains.

PMID- 16978393
TI  - Mucolipin-1 is a lysosomal membrane protein required for intracellular
      lactosylceramide traffic.
AB  - Mucolipin-1 is a membrane protein encoded by the gene MCOLN1, mutations in which
      result in the lysosomal storage disorder mucolipidosis type IV (MLIV). Efficient
      lysosomal targeting of mucolipin-1 requires di-leucine motifs in both the N
      terminal and the C-terminal cytosolic tails. We have shown that aberrant
      lactosylceramide trafficking in MLIV cells may be rescued by wild-type mucolipin
      1 expression but not by mucolipin-1 mistargeted to the plasma membrane or by
      lysosome-localized mucolipin-1 mutated in its predicted ion pore-selectivity
      region. Our data demonstrate that the correct localization of mucolipin-1 and the
      integrity of its ion pore are essential for its physiological function in the
      late endocytic pathway.

PMID- 16978396
TI  - The purpose of peer review in the case of an open-access publication.
AB  - First scientific journals were simply a way of informing colleagues about new
      research findings. In due course, they started filtering out unreasonable claims,
      and introduced a peer-review system. The purpose of peer reviewing changed with
      time. Since the middle of the past century, commercial publishers have owned a
      large number of scientific journals and as a result, the marketable value of a
      submitted manuscript has become an increasingly important factor in publishing
      decisions. Recently some publishers have developed business schemes which may
      stop this tendency. In the case of an open-access publication, the marketable
      value of a manuscript is not the primary consideration, since access to the
      research is not being sold. This innovation challenges scientists to re-consider
      the purpose of peer review. This editorial indicates some of the commonly used
      criteria for publication that consequently should receive less or little emphasis
      under the open-access model.

PMID- 16978395
TI  - Four-year follow-up of infliximab therapy in rheumatoid arthritis patients with
      long-standing refractory disease: attrition and long-term evolution of disease
      activity.
AB  - Although there is strong evidence supporting the short-term efficacy and safety
      of anti-tumour necrosis factor-alpha agents, few studies have examined the long
      term effects. We evaluated 511 patients with long-standing refractory rheumatoid
      arthritis treated with intravenous infusions of infliximab 3 mg/kg at weeks 0, 2,
      6, and 14 and every 8 weeks thereafter for 4 years. Among the initial 511
      patients included in the study, 479 could be evaluated; of these, 295 (61.6%)
      were still receiving infliximab treatment at year 4 of follow-up. The most common
      reasons for treatment discontinuation were lack of efficacy (65 patients, 13.6%),
      safety (81 patients, 16.9%), and elective change (38 patients, 7.9%). Analysis of
      disease activity scores (DAS28 [disease activity score based on the 28-joint
      count]) over time showed that, after the initial rapid improvement during the
      first 6 to 22 weeks of therapy, a further decrease in disease activity of 0.2
      units in the DAS28 score per year was observed. DAS28 scores, measured at week 14
      or 22, were found to predict subsequent discontinuation due to lack of efficacy.
      In conclusion, long-term maintenance therapy with infliximab 3 mg/kg is effective
      in producing further reductions in disease activity. Disease activity measured by
      the DAS28 at week 14 or 22 of infliximab therapy was the best predictor of long
      term attrition.

PMID- 16978397
TI  - Breastfeeding, infant formula supplementation, and Autistic Disorder: the results
      of a parent survey.
AB  - BACKGROUND: Although Autistic Disorder is associated with several congenital
      conditions, the cause for most cases is unknown. The present study was undertaken
      to determine whether breastfeeding or the use of infant formula supplemented with
      docosahexaenoic acid and arachidonic acid is associated with Autistic Disorder.
      The hypothesis is that breastfeeding and use of infant formula supplemented with
      docosahexaenoic acid/arachidonic acid are protective for Autistic Disorder.
      METHODS: This is a case-control study using data from the Autism Internet
      Research Survey, an online parental survey conducted from February to April 2005
      with results for 861 children with Autistic Disorder and 123 control children.
      The analyses were performed using logistic regression. RESULTS: Absence of
      breastfeeding when compared to breastfeeding for more than six months was
      significantly associated with an increase in the odds of having autistic disorder
      when all cases were considered (OR 2.48, 95% CI 1.42, 4.35) and after limiting
      cases to children with regression in development (OR 1.95, 95% CI 1.01, 3.78).
      Use of infant formula without docosahexaenoic acid and arachidonic acid
      supplementation versus exclusive breastfeeding was associated with a significant
      increase in the odds of autistic disorder when all cases were considered (OR
      4.41, 95% CI 1.24, 15.7) and after limiting cases to children with regression in
      development (OR 12.96, 95% CI 1.27, 132). CONCLUSION: The results of this
      preliminary study indicate that children who were not breastfed or were fed
      infant formula without docosahexaenoic acid/arachidonic acid supplementation were
      significantly more likely to have autistic disorder.

PMID- 16978398
TI  - Feasibility and long-term results of focused radioguided parathyroidectomy using
      a "low" 37 MBq (1 mCi) 99mTc-sestamibi protocol.
AB  - Aim of the present study was to investigate the feasibility and long-term results
      of focused radioguided parathyroidectomy using a "low" 37 MBq (1 mCi) 99mTc
      sestamibi dose protocol compared to conventional "high 740 MBq (20 mCi) 99mTc
      sestamibi dose protocol" in patients with primary hyperparathyroidism (PHPT). The
      data of focused radioguided surgery obtained in a group of 320 consecutive PHPT
      patients with high probability of the presence of a solitary parathyroid adenoma
      (PA) were studied. All patients underwent preoperative imaging work-up of double
      tracer 99mTc-pertechnetate/99mTc-sestamibi subtraction parathyroid scintigraphy
      (Sestamibi scintigraphy) and high resolution neck ultrasound (US). In 301/320
      patients (96.6%) focused minimally invasive radioguided surgery was successfully
      performed by administering a "low" 37 MBq (1 mCi) 99mTc-sestamibi dose in the
      operating room 10 minutes before operation. No major intraoperative complications
      were recorded. Focused radioguided surgery required a mean time of 32 min and a
      mean hospital stay of 1.2 days. Local anesthesia was applied in 75 patients, 66
      of whom (88%) were patients older than 65 years with comorbidities
      contraindicating general anesthesia. No case of persistent or recurrent PHPT was
      observed during post-surgical follow-up (range = 18-70 months; mean +/- SD = 15.3
      +/- 9.1 months). Radiation exposure dose to the operating surgeon was 1.2
      microSi/hour with the "low 37 MBq (1 mCi) 99mTc-sestamibi dose", and less than
      1.0 microSi/hour for the other operating-room personnel. Focused low dose
      radioguided parathyroidectomy is a safe and effective means to localize
      parathyroid adenomas in patients affected by solitary PA thus reducing by 20 fold
      the radiation exposure dose to the patients and operating room personnel.

PMID- 16978399
TI  - Identification of genes associated with cisplatin resistance in human oral
      squamous cell carcinoma cell line.
AB  - BACKGROUND: Cisplatin is widely used for chemotherapy of head and neck squamous
      cell carcinoma. However, details of the molecular mechanism responsible for
      cisplatin resistance are still unclear. The aim of this study was to identify the
      expression of genes related to cisplatin resistance in oral squamous cell
      carcinoma cells. METHODS: A cisplatin-resistant cell line, Tca/cisplatin, was
      established from a cisplatin-sensitive cell line, Tca8113, which was derived from
      moderately-differentiated tongue squamous cell carcinoma. Global gene expression
      in this resistant cell line and its sensitive parent cell line was analyzed using
      Affymetrix HG-U95Av2 microarrays. Candidate genes involved in DNA repair, the MAP
      pathway and cell cycle regulation were chosen to validate the microarray analysis
      results. Cell cycle distribution and apoptosis following cisplatin exposure were
      also investigated. RESULTS: Cisplatin resistance in Tca/cisplatin cells was
      stable for two years in cisplatin-free culture medium. The IC50 for cisplatin in
      Tca/cisplatin was 6.5-fold higher than that in Tca8113. Microarray analysis
      identified 38 genes that were up-regulated and 25 that were down-regulated in
      this cell line. Some were novel candidates, while others are involved in well
      characterized mechanisms that could be relevant to cisplatin resistance, such as
      RECQL for DNA repair and MAP2K6 in the MAP pathway; all the genes were further
      validated by Real-time PCR. The cell cycle-regulated genes CCND1 and CCND3 were
      involved in cisplatin resistance; 24-hour exposure to 10 microM cisplatin induced
      a marked S phase block in Tca/cisplatin cells but not in Tca8113 cells.
      CONCLUSION: The Tca8113 cell line and its stable drug-resistant variant
      Tca/cisplatin provided a useful model for identifying candidate genes responsible
      for the mechanism of cisplatin resistance in oral squamous cell carcinoma. Our
      data provide a useful basis for screening candidate targets for early diagnosis
      and further intervention in cisplatin resistance.

PMID- 16978401
TI  - Structure, (governance) and health: an unsolicited response.
AB  - BACKGROUND: In a recently published article, it was suggested that governance was
      the significant structural factor affecting the epidemiology of HIV. This
      suggestion was made notwithstanding the observed weak correlation between
      governance and HIV prevalence (r = .2). Unfortunately, the paper raised but left
      unexamined the potentially more important questions about the relationship
      between the broader health of populations and structural factors such as the
      national economy and physical infrastructure. METHODS: Utilizing substantially
      the same data sources as the original article, the relationship between
      population health (healthy life expectancy) and three structural factors (access
      to improved water, GDP per capita, and governance) were examined in each of 176
      countries. RESULTS: Governance was found to be significantly correlated with
      population health, as were GDP per capita, and access to improved water. They
      were also found to be significantly correlated with each other. CONCLUSION: The
      findings are discussed with reference to the growing interest in structural
      factors as an explanation for population health outcomes, and the relatively weak
      relationship between governance and HIV prevalence.

PMID- 16978400
TI  - Trastuzumab in combination with metronomic cyclophosphamide and methotrexate in
      patients with HER-2 positive metastatic breast cancer.
AB  - BACKGROUND: HER2/neu overexpression is linked to promotion of angiogenesis in
      breast cancer. We therefore tested the activity of the combination of Trastuzumab
      with metronomic, low dose chemotherapy with cyclophosphamide (CTX) and
      methotrexate (MTX) in metastatic breast cancer (MBC). METHODS: Between April 2002
      and June 2005, twenty-two patients with metastatic breast cancer with the
      presence of overexpression or amplification of HER2-/neu, all pre-treated with
      trastuzumab plus other cytotoxics, were treated with trastuzumab (6 mg/kg every
      three weeks) in combination with metronomic chemotherapy (MTX 2.5 mg, bid on Day
      1 and Day 4 every week) and CTX (50 mg daily) (CM). RESULTS: The 22 enrolled
      patients are evaluable: most had an ECOG performance status of 0 (17 pts), and
      all were pre-treated with chemotherapy for metastatic disease; 14 had progressive
      disease at study entry, and 11 had progressive disease during the last
      trastuzumab therapy. Metastatic sites included: lung (5 pts), liver (14 pts),
      bone (12 pts), lymph nodes (8 pts), central nervous system (CNS) (9 pts). We
      observed 4 partial remission (PR) (18%, 95% CI 5-40%), 10 stable disease (SD)
      (46%, 95% CI 24-68%), and 8 PD (36%, CI 17-59%). The clinical benefit (RP plus RC
      plus SD for > or = 24 weeks) in all pts and in pts with disease resistant to
      previous trastuzumab therapy were 46% (95% CI, 24-68%) and 27% (95% CI, 6-61%),
      respectively. Median time to progression was 6 months and median duration of
      treatment was 5 months (range, 0,7 to 18.4 months and range, 1 to 18 months,
      respectively). Overall clinical toxicity was generally mild. Grade > or =2
      reversible liver toxicity and leukopenia were reported in 5 and 3 pts,
      respectively. CONCLUSION: The combination of trastuzumab and metronomic
      chemotherapy is effective and minimally toxic in advanced breast cancer patients.
      The efficacy observed in patients with disease resistant to trastuzumab supports
      the need of larger trial to confirm a role of this combination to delay acquired
      trastuzumab resistance.

PMID- 16978402
TI  - Colonic carcinoma with multiple small bowel perforations mimicking intestinal
      obstruction.
AB  - BACKGROUND: Carcinoma of the colon may present with perforation proximal to the
      site of malignancy. Caecum is the commonest site of perforation if the ileocecal
      valve is patent and the jejunal and ileal perforations are very rare. CASE
      PRESENTATION: A 35 year male presented with intestinal obstruction. Emergency
      laparotomy revealed carcinoma of the transverse colon with multiple pinpoint
      perforations along antimesenteric border of ileum, which were wrapped with
      omentum, and no peritoneal contamination was present. Extended right
      hemicolectomy with jejunocolic anastomosis was done. Patient made uneventful
      recovery in postoperative period and was treated with adjuvant chemotherapy.
      CONCLUSION: Patients with colonic carcinoma and incompetent ileocecal valve may
      present with intestinal perforation. Increased intraluminal pressure and closed
      loop obstruction may lead to ischemia and perforation of the small bowel.

PMID- 16978403
TI  - Dibenzazecine compounds with a novel dopamine/5HT2A receptor profile and 3D-QSAR
      analysis.
AB  - BACKGROUND: Antipsychotics are divided into typical and atypical compounds based
      on clinical efficacy and side effects. The purpose of this study was to
      characterize in vitro a series of novel azecine-type compounds at human dopamine
      D1-D5 and 5HT2A receptors and to assign them to different classes according to
      their dopamine/5HT2A receptor profile. RESULTS: Regardless of using affinity data
      (pKi values at D1-D5 and 5HT2A) or selectivity data (15 log (Ki ratios)),
      principal component analysis with azecine-type compounds, haloperidol, and
      clozapine revealed three groups of dopamine/5HT2A ligands: 1) haloperidol; 2)
      clozapine plus four azecine-type compounds; 3) two hydroxylated dibenzazecines.
      Reducing the number of Ki ratios used for principal component analysis from 15 to
      two (the D1/D2 and D2/5HT2A Ki ratios) obtained the same three groups of
      compounds. The most potent dibenzazecine clustering in the same group as
      clozapine was the non-hydroxylated LE410 which shows a slightly different D2-like
      receptor profile (D2L > D3 > D4.4) than clozapine (D4.4 > D2L > D3). The
      monohydroxylated dibenzacezine LE404 clusters in a separate group from
      clozapine/LE410 and from haloperidol and shows increased D1 selectivity.
      CONCLUSION: In conclusion, two compounds with a novel dopamine/5HT2A receptor
      profile, LE404 and LE410, with some differences in their respective D1/D2
      receptor affinities including a validated pharmacophore-based 3D-QSAR model for
      D1 antagonists are presented.

PMID- 16978404
TI  - Analysis of patient flows for orthopedic procedures using small area analysis in
      Switzerland.
AB  - BACKGROUND: In general cantons regulate and control the Swiss health service
      system; patient flows within and between cantons are thereby partially
      disregarded. This paper develops an alternative spatial model, based upon the
      construction of orthopedic hospital service areas (HSAOs), and introduces indices
      for the analysis of patient streams in order to identify areas, irrespective of
      canton, with diverse characteristics, importance, needs, or demands. METHODS:
      HSAOs were constructed using orthopedic discharge data. Patient streams between
      the HSAOs were analysed by calculating three indices: the localization index (%
      local residents discharged locally), the netindex (the ratio of discharges of
      nonlocal incoming residents to outgoing local residents), and the market share
      index (% of local resident discharges of all discharges in local hospitals).
      RESULTS: The 85 orthopedic HSAOs show a median localization index of 60.8%, a
      market share index of 75.1%, and 30% of HSAOs have a positive netindex. Insurance
      class of bed, admission type, and patient age are partially but significantly
      associated with those indicators. A trend to more centrally provided health
      services can be observed not only in large urban HSAOs such as Geneva, Bern,
      Basel, and Zurich, but also in HSAOs in mountain sport areas such as Sion, Davos,
      or St.Moritz. Furthermore, elderly and emergency patients are more frequently
      treated locally than younger people or those having elective procedures.
      CONCLUSION: The division of Switzerland into HSAOs provides an alternative
      spatial model for analysing and describing patient streams for health service
      utilization. Because this small area model allows more in-depth analysis of
      patient streams both within and between cantons, it may improve support and
      planning of resource allocation of in-patient care in the Swiss healthcare
      system.

PMID- 16978405
TI  - Plummer-Vinson syndrome.
AB  - Plummer-Vinson or Paterson-Kelly syndrome presents as a classical triad of
      dysphagia, iron-deficiency anemia and esophageal webs. Exact data about
      epidemiology of the syndrome are not available; the syndrome is extremely rare.
      Most of the patients are white middle-aged women, in the fourth to seventh decade
      of life but the syndrome has also been described in children and adolescents. The
      dysphagia is usually painless and intermittent or progressive over years, limited
      to solids and sometimes associated with weight loss. Symptoms resulting from
      anemia (weakness, pallor, fatigue, tachycardia) may dominate the clinical
      picture. Additional features are glossitis, angular cheilitis and koilonychia.
      Enlargement of the spleen and thyroid may also be observed. One of the most
      important clinical aspects of Plummer-Vinson syndrome is the association with
      upper alimentary tract cancers. Etiopathogenesis of Plummer-Vinson syndrome is
      unknown. The most important possible etiological factor is iron deficiency. Other
      possible factors include malnutrition, genetic predisposition or autoimmune
      processes. Plummer-Vinson syndrome can be treated effectively with iron
      supplementation and mechanical dilation. In case of significant obstruction of
      the esophageal lumen by esophageal web and persistent dysphagia despite iron
      supplementation, rupture and dilation of the web are necessary. Since Plummer
      Vinson syndrome is associated with an increased risk of squamous cell carcinoma
      of the pharynx and the esophagus, the patients should be followed closely.

PMID- 16978406
TI  - The conserved dileucine- and tyrosine-based motifs in MLV and MPMV envelope
      glycoproteins are both important to regulate a common Env intracellular
      trafficking.
AB  - BACKGROUND: Retrovirus particles emerge from the assembly of two structural
      protein components, Gag that is translated as a soluble protein in the cytoplasm
      of the host cells, and Env, a type I transmembrane protein. Because both
      components are translated in different intracellular compartments, elucidating
      the mechanisms of retrovirus assembly thus requires the study of their
      intracellular trafficking. RESULTS: We used a CD25 (Tac) chimera-based approach
      to study the trafficking of Moloney murine leukemia virus and Mason-Pfizer monkey
      virus Env proteins. We found that the cytoplasmic tails (CTs) of both Env
      conserved two major signals that control a complex intracellular trafficking. A
      dileucine-based motif controls the sorting of the chimeras from the trans-Golgi
      network (TGN) toward endosomal compartments. Env proteins then follow a
      retrograde transport to the TGN due to the action of a tyrosine-based motif.
      Mutation of either motif induces the mis-localization of the chimeric proteins
      and both motifs are found to mediate interactions of the viral CTs with clathrin
      adaptors. CONCLUSION: This data reveals the unexpected complexity of the
      intracellular trafficking of retrovirus Env proteins that cycle between the TGN
      and endosomes. Given that Gag proteins hijack endosomal host proteins, our work
      suggests that the endosomal pathway may be used by retroviruses to ensure proper
      encountering of viral structural Gag and Env proteins in cells, an essential step
      of virus assembly.

PMID- 16978407
TI  - A fatal pseudo-tumour: disseminated basidiobolomycosis.
AB  - BACKGROUND: Basidiobolomycosis is a rare disease caused by the fungus
      Basidiobolus ranarum, member of the class Zygomycetes, order Entomophthorales,
      found worldwide. Usually basidiobolomycosis is a subcutaneous infection but
      rarely gastrointestinal manifestations have been described; 13 adults and 10
      children and a few retroperitoneal or pulmonary cases. In gastrointestinal
      basidiobolomycosis the colon is most frequently involved, usually presenting with
      subacute mild abdominal pain. In contrast to children only very few described
      adult patients had hepatic masses. Definitive diagnosis requires culture,
      serological testing can be helpful. The fungal morphology and the Splendore
      Hoeppli phenomenon are characteristic histological features. There are no
      prominent risk factors. Usually surgery and prolonged antifungal therapy are
      required. CASE PRESENTATION: A 61 year old man presented with progressive left
      abdominal pain and constipation since a few months. Colonoscopy showed an
      obstructing tumour in the descending colon, and a hemicolectomy was performed.
      Histology showed inflammation, possibly caused by a fungal or parasitic
      infection, without definite identification of an organism. A few weeks
      postoperatively a CT scan made because of abdominal discomfort, revealed a
      livermass (6 cm). Treatment with metronidazole, directed against an amoebic liver
      abscess, was unsuccessful. He developed a marked eosinophilia (27.7%). A liver
      biopsy was performed and the patient was referred to a university hospital.A
      repeated CT scan showed a livermass of 9 cm diameter. Review of colon and liver
      biopsy samples showed extensive necrosis and histiocytes, multinucleated giant
      cells and numerous eosinophils. Grocott stained sections contained unusually
      large hyphae surrounded by strongly eosinophilic material in haematoxylin and
      eosin stained sections (Splendore-Hoeppli phenomenon). A presumptive diagnosis of
      Basidiobolus spp. infection was made and treated with amphotericin B (Itraconazol
      contra-indicated because of renal insufficiency). A few days later the patient
      died of a septic shock. After autopsy Basidiobolus ranarum was cultured from
      liver, gallbladder and colon. CONCLUSION: Our patient died of gastrointestinal
      basidiobolomycosis with an obstructing colon tumour and a large hepatic mass.
      This was a rare presentation of basidiobolomycosis and the second fatal case
      described worldwide.

PMID- 16978408
TI  - Normalisation of cerebrospinal fluid biomarkers parallels improvement of
      neurological symptoms following HAART in HIV dementia--case report.
AB  - BACKGROUND: Since the introduction of HAART the incidence of HIV dementia has
      declined and HAART seems to improve neurocognitive function in patients with HIV
      dementia. Currently, HIV dementia develops mainly in patients without effective
      treatment, though it has also been described in patients on HAART and milder HIV
      associated neuropsychological impairment is still frequent among HIV-1 infected
      patients regardless of HAART. Elevated cerebrospinal fluid (CSF) levels of
      markers of neural injury and immune activation have been found in HIV dementia,
      but neither of those, nor CSF HIV-1 RNA levels have been proven useful as
      diagnostic or prognostic pseudomarkers in HIV dementia. CASE PRESENTATION: We
      report a case of HIV dementia (MSK stage 3) in a 57 year old antiretroviral naive
      man who was introduced on zidovudine, lamivudine and ritonavir boosted indinavir,
      and followed with consecutive lumbar punctures before and after two and 15 months
      after initiation of HAART. Improvement of neurocognitive function was paralleled
      by normalisation of CSF neural markers (NFL, Tau and GFAP) levels and a decline
      in CSF and serum neopterin and CSF and plasma HIV-1 RNA levels. CONCLUSION: The
      value of these CSF markers as prognostic pseudomarkers of the effect of HAART on
      neurocognitive impairment in HIV dementia ought to be evaluated in longitudinal
      studies.

PMID- 16978409
TI  - DADOS-Survey: an open-source application for CHERRIES-compliant Web surveys.
AB  - BACKGROUND: The Internet has been increasingly utilized in biomedical research.
      From online searching for literature to data sharing, the Internet has emerged as
      a primary means of research for many physicians and scientists. As a result, Web
      based surveys have been employed as an alternative to traditional, paper-based
      surveys. We describe DADOS-Survey, an open-source Web-survey application
      developed at our institution that, to the best of our knowledge, is the first to
      be compliant with the Checklist for Reporting Results of Internet E-Surveys
      (CHERRIES). DADOS-Survey was designed with usability as a priority, allowing
      investigators to design and execute their own studies with minimal technical
      difficulties in doing so. RESULTS: To date, DADOS-Survey has been successfully
      implemented in five Institutional Review Board-approved studies conducted by
      various departments within our academic center. Each of these studies employed a
      Web-survey design as their primary methodology. Our initial experience indicates
      that DADOS-Survey has been used with relative ease by each of the investigators
      and survey recipients. This has been further demonstrated through formal and
      field usability testing, during which time suggestions for improvement were
      incorporated into the software design. CONCLUSION: DADOS-Survey has the potential
      to have an important role in the future direction of Web-survey administration in
      biomedical research. This CHERRIES-compliant application is tailored to the
      emerging requirements of quality data collection in medicine.

PMID- 16978411
TI  - Detection of 65 kD heat shock protein in cerebrospinal fluid of tuberculous
      meningitis patients.
AB  - BACKGROUND: Diagnosis of tuberculous meningitis (TBM) is difficult. Rapid
      confirmatory diagnosis is essential to initiate required therapy. There are very
      few published reports about the diagnostic significance of 65 kD heat shock
      protein (hsp) in TBM patients, which is present in a wide range of Mycobacterium
      tuberculosis species and elicits a cellular and humoral immune response. In the
      present study we have conducted a prospective evaluation for the demonstration of
      65 kD hsp antigen in cerebrospinal fluid (CSF) of TBM patients, by indirect ELISA
      method using monoclonal antibodies (mAb) against the 65 kD hsp antigen, for the
      diagnosis of TBM. METHODS: A total of 160 CSF samples of different groups of
      patients (confirmed TBM {n = 18}, clinically suspected TBM {n = 62}, non TBM
      infectious meningitis {n = 35} and non-infectious neurological diseases {n = 45})
      were analyzed by indirect ELISA method using mAb to 65 kD hsp antigen. The
      Kruskal Wallis test (Non-Parametric ANOVA) with the Dunnett post test was used
      for statistical analysis. RESULTS: The indirect ELISA method yielded 84%
      sensitivity and 90% specificity for the diagnosis of TBM using mAb to 65 kD hsp
      antigen. The mean absorbance value of 65 kD hsp antigen in TBM patients was [0.70
      +/- 0.23 (0.23-1.29)], significantly higher than the non-TBM infectious
      meningitis group [0.32 +/- 0.14 (0.12-0.78), P < 0.001] and also higher than the
      non-infectious neurological disorders group [0.32 +/- 0.13 (0.20-0.78), P <
      0.001]. A significant difference in the mean absorbance of 65 kD hsp antigen was
      noted in the CSF of culture-positive TBM patients [0.94 +/- 0.18 (0.54-1.29)]
      when compared with clinically suspected TBM patients [0.64 +/- 0.20 (0.23-0.98),
      P < 0.05]. CONCLUSION: The presence of 65 kD hsp antigen in the CSF of confirmed
      and suspected cases of TBM would indicate that the selected protein is specific
      to M. tuberculosis and could be considered as a diagnostic marker for TBM.

PMID- 16978410
TI  - Geometric morphometrics defines shape differences in the cortical area map of
      C57BL/6J and DBA/2J inbred mice.
AB  - BACKGROUND: We previously described planar areal differences in adult mouse
      visual, somatosensory, and neocortex that collectively discriminated C57BL/6J and
      DBA/2J inbred strain identity. Here we use a novel application of established
      methods of two-dimensional geometric morphometrics to examine shape differences
      in the cortical area maps of these inbred strains. RESULTS: We used Procrustes
      superimposition to align a reliable set of landmarks in the plane of the cortical
      sheet from tangential sections stained for the cytochrome oxidase enzyme.
      Procrustes superimposition translates landmark configurations to a common origin,
      scales them to a common size, and rotates them to minimize an estimate of error.
      Remaining variation represents shape differences. We compared the variation in
      shape between C57BL/6J and DBA/2J relative to that within each strain using a
      permutation test of Goodall's F statistic. Significant differences in shape in
      the posterior medial barrel subfield (PMBSF), as well as differences in shape
      across primary sensory areas, characterize the cortical area maps of these common
      inbred, isogenic strains. CONCLUSION: C57BL/6J and DBA/2J have markedly different
      cortical area maps, in both size and shape. These differences suggest
      polymorphism in genetic factors underlying cortical specification, even between
      common isogenic strains. Comparing cortical phenotypes between normally varying
      inbred mice or between genetically modified mice can identify genetic
      contributions to cortical specification. Geometric morphometric analysis of shape
      represents an additional quantitative tool for the study of cortical development,
      regardless of whether it is studied from phenotype to gene or gene to phenotype.

PMID- 16978412
TI  - Detection of potentially valuable polymorphisms in four group I intron insertion
      sites at the 3'-end of the LSU rDNA genes in biocontrol isolates of Metarhizium
      anisopliae.
AB  - BACKGROUND: The entomopathogenic anamorphic fungus Metarhizum anisopliae is
      currently used as a biocontrol agent (BCA) of insects. In the present work, we
      analyzed the sequence data obtained from group I introns in the large subunit
      (LSU) of rDNA genes with a view to determining the genetic diversity present in
      an autochthonous collection of twenty-six M. anisopliae isolates selected as
      BCAs. RESULTS: DNA fragments corresponding to the 3'-end of the nuclear LSU rDNA
      genes of 26 M. anisopliae isolates were amplified by PCR. The amplicon sizes
      ranged from 0.8 to 3.4-kb. Four intron insertion sites, according to Escherichia
      coli J01695 numbering, were detected--Ec1921, Ec2066, Ec2449 and Ec2563--after
      sequencing and analysis of the PCR products. The presence/absence of introns
      allowed the 26 isolates to be distributed into seven genotypes. Nine of the
      isolates tested showed no introns, 4 had only one, 3 two, and 10 displayed three
      introns. The most frequent insertion sites were Ec1921 and Ec2449. Of the 26
      isolates, 11 showed insertions at Ec2563 and a 1754-bp sequence was observed in
      ten of them. The most-parsimonious (MP) tree obtained from parsimony analysis of
      the introns revealed a main set containing four-groups that corresponded to the
      four insertion sites. CONCLUSION: Four insertion sites of group I introns in the
      LSU rDNA genes allowed the establishment of seven genotypes among the twenty-six
      biocontrol isolates of M. anisopliae. Intron insertions at the Ec2563 site were
      observed for first time in this species.

PMID- 16978414
TI  - Comparison of geometric morphometric outline methods in the discrimination of age
      related differences in feather shape.
AB  - BACKGROUND: Geometric morphometric methods of capturing information about curves
      or outlines of organismal structures may be used in conjunction with canonical
      variates analysis (CVA) to assign specimens to groups or populations based on
      their shapes. This methodological paper examines approaches to optimizing the
      classification of specimens based on their outlines. This study examines the
      performance of four approaches to the mathematical representation of outlines and
      two different approaches to curve measurement as applied to a collection of
      feather outlines. A new approach to the dimension reduction necessary to carry
      out a CVA on this type of outline data with modest sample sizes is also
      presented, and its performance is compared to two other approaches to dimension
      reduction. RESULTS: Two semi-landmark-based methods, bending energy alignment and
      perpendicular projection, are shown to produce roughly equal rates of
      classification, as do elliptical Fourier methods and the extended eigenshape
      method of outline measurement. Rates of classification were not highly dependent
      on the number of points used to represent a curve or the manner in which those
      points were acquired. The new approach to dimensionality reduction, which
      utilizes a variable number of principal component (PC) axes, produced higher
      cross-validation assignment rates than either the standard approach of using a
      fixed number of PC axes or a partial least squares method. CONCLUSION:
      Classification of specimens based on feather shape was not highly dependent of
      the details of the method used to capture shape information. The choice of
      dimensionality reduction approach was more of a factor, and the cross validation
      rate of assignment may be optimized using the variable number of PC axes method
      presented herein.

PMID- 16978413
TI  - Cis-regulatory variations: a study of SNPs around genes showing cis-linkage in
      segregating mouse populations.
AB  - BACKGROUND: Changes in gene expression are known to be responsible for phenotypic
      variation and susceptibility to diseases. Identification and annotation of the
      genomic sequence variants that cause gene expression changes is therefore likely
      to lead to a better understanding of the cause of disease at the molecular level.
      In this study we investigate the pattern of single nucleotide polymorphisms
      (SNPs) in genes for which the mRNA levels show cis-genetic linkage (gene
      expression quantitative trait loci mapping in cis, or cis-eQTLs) in segregating
      mouse populations. Such genes are expected to have polymorphisms near their
      physical location (cis-variations) that affect their mRNA levels by altering one
      or more of the cis-regulatory elements. This led us to characterize the SNPs in
      promoter (5 Kb upstream) and non-coding gene regions (introns and 5 Kb
      downstream) (cis-SNPs) and the effects they may have on putative transcription
      factor binding sites. RESULTS: We demonstrate that the cis-eQTL genes (CEGs) have
      a significantly higher frequency of cis-SNPs compared to non-CEGs (when both sets
      are taken from the non-IBD regions, i.e. regions not identical by descent). Most
      CEGs having cis-SNPs do not contain these SNPs in the phylogenetically conserved
      regions. In those CEGs that contain cis-SNPs in the phylogenetically conserved
      regions, enrichment of cis-SNPs occurs both within and outside of the conserved
      sequences. A higher fraction of CEGs are also seen to harbor cis-SNP that affect
      predicted transcription factor binding sites, a likely consequence of the higher
      cis-SNPs density in these genes. CONCLUSION: This present study provides the
      first genome-wide investigation of the putative cis-regulatory variations in a
      large set of genes whose levels of expression give rise to cis-linkage in
      segregating mammalian populations. Our results provide insights into the
      challenges that exist in identifying polymorphisms regulating gene expression
      using bioinformatic sequence analysis approaches. The data provided herein should
      benefit future investigations in this area.

PMID- 16978416
TI  - Clipless management of the renal vein during hand-assist laparoscopic donor
      nephrectomy.
AB  - BACKGROUND: Laparoscopic live donor nephrectomy has become the preferred method
      of donor nephrectomy at many transplant centers. The laparoscopic stapling device
      is commonly used for division of the renal vessels. Malfunction of the stapling
      device can occur, and is often due to interference from previously placed clips.
      We report our experience with a clipless technique in which no vascular clips are
      placed on tributaries of the renal vein at or near the renal hilum in order to
      avoid laparoscopic stapling device misfires. METHODS: From December 20, 2002 to
      April 12, 2005, 50 patients underwent hand-assisted laparoscopic left donor
      nephrectomy (LDN) at our institution. Clipless management of the renal vein
      tributaries was used in all patients, and these vessels were divided using either
      a laparoscopic stapling device or the LigaSureTM device (Valleylab, Boulder, CO).
      The medical and operative records of the donors and recipients were reviewed to
      evaluate patient outcomes. RESULTS: The mean follow-up time was 14 months. Of the
      50 LDN procedures, there were no laparoscopic stapling device malfunctions and no
      vascular complications. All renal allografts were functioning at the time of
      follow-up. CONCLUSION: Laparoscopic stapling device failure due to deployment
      across previously placed surgical clips during laparoscopic live donor
      nephrectomy can be prevented by not placing clips on the tributaries of the renal
      vein. In our series, there were no vascular complications and no device misfires.
      We believe this clipless technique improves the safety of laparoscopic donor
      nephrectomy.

PMID- 16978415
TI  - Serum neuron-specific enolase as early predictor of outcome after in-hospital
      cardiac arrest: a cohort study.
AB  - INTRODUCTION: Outcome after cardiac arrest is mostly determined by the degree of
      hypoxic brain damage. Patients recovering from cardiopulmonary resuscitation are
      at great risk of subsequent death or severe neurological damage, including
      persistent vegetative state. The early definition of prognosis for these patients
      has ethical and economic implications. The main purpose of this study was to
      investigate the prognostic value of serum neuron-specific enolase (NSE) in
      predicting outcomes in patients early after in-hospital cardiac arrest. METHODS:
      Forty-five patients resuscitated from in-hospital cardiac arrest were
      prospectively studied from June 2003 to January 2005. Blood samples were
      collected, at any time between 12 and 36 hours after the arrest, for NSE
      measurement. Outcome was evaluated 6 months later with the Glasgow outcome scale
      (GOS). Patients were divided into two groups: group 1 (unfavorable outcome)
      included GOS 1 and 2 patients; group 2 (favorable outcome) included GOS 3, 4 and
      5 patients. The Mann-Whitney U test, Student's t test and Fisher's exact test
      were used to compare the groups. RESULTS: The Glasgow coma scale scores were 6.1
      +/- 3 in group 1 and 12.1 +/- 3 in group 2 (means +/- SD; p < 0.001). The mean
      time to NSE sampling was 20.2 +/- 8.3 hours in group 1 and 28.4 +/- 8.7 hours in
      group 2 (p = 0.013). Two patients were excluded from the analysis because of
      sample hemolysis. At 6 months, favorable outcome was observed in nine patients
      (19.6%). Thirty patients (69.8%) died and four (9.3%) remained in a persistent
      vegetative state. The 34 patients (81.4%) in group 1 had significantly higher NSE
      levels (median 44.24 ng/ml, range 8.1 to 370) than those in group 2 (25.26 ng/ml,
      range 9.28 to 55.41; p = 0.034). CONCLUSION: Early determination of serum NSE
      levels is a valuable ancillary method for assessing outcome after in-hospital
      cardiac arrest.

PMID- 16978417
TI  - Long-term outcome and quality of life of patients treated in surgical intensive
      care: a comparison between sepsis and trauma.
AB  - INTRODUCTION: Our aim was to determine long-term survival and quality of life of
      patients admitted to a surgical intensive care unit (ICU) because of sepsis or
      trauma. METHODS: This was an observational study conducted in an 11-bed, closed
      surgical ICU at a 860-bed teaching general hospital over a 1-year period (January
      2003 to December 2003). Patients were divided into two groups according to
      admission diagnoses: group 1 included patients with sepsis; and group 2 included
      patients with trauma (polytrauma, multiple trauma, head injury, or spinal
      injury). Quality of life was assessed after 2 years following ICU admission using
      the EuroQol 5D questionnaire. RESULTS: A total of 164 patients (98 trauma
      patients and 66 patients with sepsis) were included in the study. Trauma patients
      were younger than patients with sepsis (53 +/- 21 years versus 64 +/- 13 years; P
      < or = 0.001). There was no significant difference between groups in Acute
      Physiology and Chronic Health Evaluation II score or length of stay in the
      surgical SICU. Trauma patients stayed longer on the general ward (35 +/- 44 days
      versus 17 +/- 24 days; P < 001). Surgical ICU survival, in-hospital survival, and
      post-hospital and cumulative 2-year survival were lower in the sepsis group than
      in the trauma group (surgical ICU survival: 60% versus 74%; in-hospital survival:
      42% versus 62%; post-hospital survival: 78% versus 92%; cumulative 2-year
      survival: 33% versus 57%; P < 0.05). There was no significant difference in
      quality of life in all five dimensions of the EuroQol 5D between groups: 60% of
      patients had signs of depression, almost 60% had problems in usual activities and
      56% had pain. CONCLUSION: Patients with sepsis treated in a surgical ICU have
      higher short-term and long-term mortality than do trauma patients. However,
      quality of life is reduced to the same level in both groups.

PMID- 16978418
TI  - Plasma membrane calcium ATPase (PMCA4): a housekeeper for RT-PCR relative
      quantification of polytopic membrane proteins.
AB  - BACKGROUND: Although relative quantification of real-time RT-PCR data can provide
      valuable information, one limitation remains the selection of an appropriate
      reference gene. No one gene has emerged as a universal reference gene and much
      debate surrounds some of the more commonly used reference genes, such as
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH). At this time, no gene encoding
      for a plasma membrane protein serves as a reference gene, and relative
      quantification of plasma membrane proteins is performed with genes encoding
      soluble proteins, which differ greatly in quantity and in targeting and
      trafficking from plasma membrane proteins. In this work, our aim was to identify
      a housekeeping gene, ideally one that codes for a plasma membrane protein, whose
      expression remains the same regardless of drug treatment and across a wide range
      of tissues to be used for relative quantification of real-time RT-PCR data for
      ATP binding cassette (ABC) plasma membrane transporters. RESULTS: In studies
      evaluating the expression levels of two commonly used reference genes coding for
      soluble proteins and two genes coding for membrane proteins, one plasma membrane
      protein, plasma membrane calcium-ATPase 4 (PMCA4), was comparable to the two
      reference genes already in use. In addition, PMCA4 expression shows little
      variation across eight drug-treated cell lines and was found to be superior to
      GAPDH and HPRT1, commonly used reference genes. Finally, we show PMCA4 used as a
      reference gene for normalizing ABC transporter expression in a drug-resistant
      lung carcinoma cell line. CONCLUSION: We have found that PMCA4 is a good
      housekeeping gene for normalization of gene expression for polytopic membrane
      proteins including transporters and receptors.

PMID- 16978419
TI  - M. leprae inhibits apoptosis in THP-1 cells by downregulation of Bad and Bak and
      upregulation of Mcl-1 gene expression.
AB  - BACKGROUND: Virulent Mycobacterium leprae interfere with host defense mechanisms
      such as cytokine activation and apoptosis. The mitochondrial pathway of apoptosis
      is regulated by the Bcl-2 family of proteins. Expression of Fas ligand and
      apoptotic proteins is found in leprosy lesions and M. leprae has been shown to
      activate pro-apoptotic Bcl-2 genes, Bak and Bax. However, the mechanism by which
      M. leprae modulates apoptosis is as yet unclear. We investigated expression of
      apoptotic genes in THP-1 monocytes in response to infection by M. leprae and non
      pathogenic M. bovis BCG. RESULTS: M. leprae did not induce apoptosis in THP-1
      cells, while BCG induced a significant loss of cell viability by 18 h post
      infection at both (multiplicity of infection) MOI-10 and 20, with an increase by
      48 h. BCG-induced cell death was accompanied by characteristic apoptotic DNA
      laddering in cells. Non-viable BCG had a limited effect on host cell death
      suggesting that BCG-induced apoptosis was a function of mycobacterial viability.
      M. leprae also activated lower levels of TNF-alpha secretion and TNF-alpha mRNA
      expression than BCG. Mycobacterium-induced activation of apoptotic gene
      expression was determined over a time course of infection. M. leprae reduced Bad
      and Bak mRNA expression by 18 h post-stimulation, with a further decrease at 48
      h. Outcome of cell viability is determined by the ratio between pro- and anti
      apoptotic proteins present in the cell. M. leprae infection resulted in
      downregulation of gene expression ratios, Bad/Bcl-2 mRNA by 39% and Bak/Bcl-2
      mRNA by 23%. In contrast, live BCG increased Bad/Bcl-2 mRNA (29 %) but had a
      negligible effect on Bak/Bcl-2 mRNA. Heat killed BCG induced only a negligible (1
      4 %) change in mRNA expression of either Bak/Bcl-2 or Bad/Bcl-2. Additionally, M.
      leprae upregulated the expression of anti-apoptotic gene Mcl-1 while, BCG
      downregulated Mcl-1 mRNA. CONCLUSION: This study proposes an association between
      mycobacterium-induced apoptosis in THP-1 cells and the regulation of Bcl-2 family
      of proteins. M. leprae restricts apoptosis in THP-1 cells by downregulation of
      Bad and Bak and upregulation of Mcl-1 mRNA expression.

PMID- 16978420
TI  - Stenotrophomonas maltophilia resistant to trimethoprim-sulfamethoxazole: an
      increasing problem.
AB  - Stenotrophomonas maltophilia (S. maltophilia) has recently emerged as an
      important nosocomial pathogen. Treatment of invasive infections caused by this
      organism is difficult as the bacterium is frequently resistant to a wide range of
      commonly used antimicrobials. Trimethoprim-sulfamethoxazole (TMP - SXT) is
      recommended as the agent of choice for the treatment of S. maltophilia
      infections. However, the development of resistance to this antibiotic represents
      a real challenge to laboratorians and clinicians. This letter describes the first
      isolation of S. maltophilia resistant to TMP - SXT from two patients treated at
      Riyadh Armed Forces Hospital which is a major tertiary hospital in Saudi Arabia.

PMID- 16978421
TI  - miTarget: microRNA target gene prediction using a support vector machine.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small noncoding RNAs, which play significant
      roles as posttranscriptional regulators. The functions of animal miRNAs are
      generally based on complementarity for their 5' components. Although several
      computational miRNA target-gene prediction methods have been proposed, they still
      have limitations in revealing actual target genes. RESULTS: We implemented
      miTarget, a support vector machine (SVM) classifier for miRNA target gene
      prediction. It uses a radial basis function kernel as a similarity measure for
      SVM features, categorized by structural, thermodynamic, and position-based
      features. The latter features are introduced in this study for the first time and
      reflect the mechanism of miRNA binding. The SVM classifier produces high
      performance with a biologically relevant data set obtained from the literature,
      compared with previous tools. We predicted significant functions for human miR-1,
      miR-124a, and miR-373 using Gene Ontology (GO) analysis and revealed the
      importance of pairing at positions 4, 5, and 6 in the 5' region of a miRNA from a
      feature selection experiment. We also provide a web interface for the program.
      CONCLUSION: miTarget is a reliable miRNA target gene prediction tool and is a
      successful application of an SVM classifier. Compared with previous tools, its
      predictions are meaningful by GO analysis and its performance can be improved
      given more training examples.

PMID- 16978422
TI  - Radically different maxicircle classes within the same kinetoplast: an artefact
      or a novel feature of the kinetoplast genome?
AB  - We discuss here some results which suggest that radically different maxicircle
      classes coexist within the same kinetoplast. These data, although tentative and
      incomplete, may provide a new outlook on the kinetoplast genome structure and
      expression.

PMID- 16978423
TI  - Detecting recombination in evolving nucleotide sequences.
AB  - BACKGROUND: Genetic recombination can produce heterogeneous phylogenetic
      histories within a set of homologous genes. These recombination events can be
      obscured by subsequent residue substitutions, which consequently complicate their
      detection. While there are many algorithms for the identification of
      recombination events, little is known about the effects of subsequent
      substitutions on the accuracy of available recombination-detection approaches.
      RESULTS: We assessed the effect of subsequent substitutions on the detection of
      simulated recombination events within sets of four nucleotide sequences under a
      homogeneous evolutionary model. The amount of subsequent substitutions per site,
      prior evolutionary history of the sequences, and reciprocality or non
      reciprocality of the recombination event all affected the accuracy of the
      recombination-detecting programs examined. Bayesian phylogenetic-based approaches
      showed high accuracy in detecting evidence of recombination event and in
      identifying recombination breakpoints. These approaches were less sensitive to
      parameter settings than other methods we tested, making them easier to apply to
      various data sets in a consistent manner. CONCLUSION: Post-recombination
      substitutions tend to diminish the predictive accuracy of recombination-detecting
      programs. The best method for detecting recombined regions is not necessarily the
      most accurate in identifying recombination breakpoints. For difficult detection
      problems involving highly divergent sequences or large data sets, different types
      of approach can be run in succession to increase efficiency, and can potentially
      yield better predictive accuracy than any single method used in isolation.

PMID- 16978424
TI  - Life after your primary career.

PMID- 16978425
TI  - Cerebral hemodynamics in preeclampsia: cerebral perfusion and the rationale for
      an alternative to magnesium sulfate.
AB  - Preeclampsia and eclampsia continue to be major causes of maternal death.
      Currently, approximately 18% of U.S. maternal deaths are attributed to
      hypertensive disorders and eclampsia, and several hundred women die from
      eclampsia and its complications every year. In the United States, preeclamptic
      women have received magnesium sulfate as a seizure prophylaxis agent for 3
      decades, and this practice is becoming more widely accepted internationally. In
      addition to a recognized failure rate, there are financial, logistic, and safety
      concerns associated with the universal administration of magnesium sulfate. Many
      institutions in the developing world lack the necessary equipment and expertise
      to administer the medication, and many preeclamptic patients thus do not receive
      magnesium sulfate before their first seizure. As effective as it has been in
      reducing mortality from eclampsia, magnesium sulfate is also associated with
      appreciable morbidity and mortality from administration errors and magnesium
      toxicity. The availability of an easily administered, cheap, safe, and orally
      administered alternative to magnesium sulfate would be welcomed in the developing
      world and would provide an extremely useful alternative therapy to the current
      standard of care. Recent advances in the understanding of the pathophysiology of
      preeclampsia and eclampsia, primarily related to cerebral perfusion and blood
      flow, could allow us to reduce the seizure rate in treated preeclamptic women
      even further than what is currently reported. This article deals with the
      rationale behind the use of labetalol as an alternative to magnesium sulfate for
      the prevention of eclampsia. TARGET AUDIENCE: Obstetricians & Gynecologists,
      Family Physicians. LEARNING OBJECTIVES: After completion of this article, the
      reader should be able to recall that hypertensive diseases of pregnancy
      contribute a significant portion of today's maternal mortality, explain that
      methods of preventing eclampsia are not applicable worldwide, and state that
      understanding of the pathophysiology of preeclampsia/eclampsia may assist in
      developing safe and effective medications that can be used universally.

PMID- 16978426
TI  - Hepatitis C and pregnancy.
AB  - Hepatitis C is the most common chronic bloodborne infection in the United States.
      The diagnosis of vertical transmission is reliably established by a positive
      serum hepatitis C virus (HCV) RNA on 2 occasions 3 to 4 months apart after the
      infant is at least 2 months old and/or by the detection of anti-HCV antibodies
      after the infant is 18 months old. Vertical transmission in HCV RNA-negative
      pregnant women is approximately 1% to 3% versus approximately 4% to 6% in HCV RNA
      positive women. From the standpoint of vertical transmission, no critical HCV RNA
      titer has been established. Coinfection with HIV has been shown to increase the
      risk of vertical transmission of HCV, but highly active antiretroviral therapy
      may decrease the risk significantly. In HIV-negative women, route of delivery
      does not influence vertical transmission. In HCV/HIV-coinfected women, decisions
      regarding mode of delivery should be based on HIV status. There is no association
      between vertical transmission of HCV and gestational age at delivery or the
      presence of chorioamnionitis. The use of a scalp electrode has been associated
      with vertical transmission and this practice is discouraged. Data are conflicting
      regarding duration of ruptured membranes and the risk of vertical transmission of
      hepatitis C. When the duration of membrane rupture exceeds 6 hours, the risk may
      be increased. There is no evidence demonstrating an increased risk of HCV
      transmission in HIV-negative women who breast feed. In HCV/HIV-coinfected women,
      breast feeding is discouraged in women who have consistent access to safe infant
      formula. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians.
      LEARNING OBJECTIVES: After completion of this article, the reader should be able
      to recall that vertical transmission of hepatitis C (HCV) does occur, state that
      coinfection with HIV increases the transmission rate, and summarize that there is
      no association between gestational age or presence of chorioamnionitis and no
      evidence that a cesarean delivery prevents transmission.

PMID- 16978427
TI  - Hormonal therapy: does it increase or decrease cardiovascular risk?
AB  - The use of hormonal therapy (HT) has become one of the most controversial topics
      in the area of women's health. A particular area of confusion has been the issue
      of cardiovascular benefit versus cardiovascular risk for women using HT. Although
      years of observational data have suggested that women receiving HT have a lower
      incidence of coronary artery disease (CAD) and longer survival, several
      prospective, randomized controlled trials have brought this tenet into debate.
      This article provides a historical perspective on the role of HT and CAD. The
      Heart and Estrogen/Progestin Replacement Study (HERS) and the Women's Health
      Initiative (WHI) data are analyzed in conjunction with newer data. Finally, an
      explanation will be provided as to how early initiation of HT could afford
      cardiovascular protection and not contradict the HERS and WHI. TARGET AUDIENCE:
      Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After
      completion of this article, the reader should be able to state that controversy
      still remains in the use of hormonal therapy (HT) for menopause, explain that
      there are conflicting data from both prospective and observational studies, and
      recall that a new look at prospective data may indicate that HT has beneficial
      cardiovascular effects.

PMID- 16978428
TI  - Gene-environment interactions in complex diseases: genetic models and methods for
      QTL mapping in multiple half-sib populations.
AB  - An interval quantitative trait locus (QTL) mapping method for complex polygenic
      diseases (as binary traits) showing QTL by environment interactions (QEI) was
      developed for outbred populations on a within-family basis. The main objectives,
      within the above context, were to investigate selection of genetic models and to
      compare liability or generalized interval mapping (GIM) and linear regression
      interval mapping (RIM) methods. Two different genetic models were used: one with
      main QTL and QEI effects (QEI model) and the other with only a main QTL effect
      (QTL model). Over 30 types of binary disease data as well as six types of
      continuous data were simulated and analysed by RIM and GIM. Using table values
      for significance testing, results show that RIM had an increased false detection
      rate (FDR) for testing interactions which was attributable to scale effects on
      the binary scale. GIM did not suffer from a high FDR for testing interactions.
      The use of empirical thresholds, which effectively means higher thresholds for
      RIM for testing interactions, could repair this increased FDR for RIM, but such
      empirical thresholds would have to be derived for each case because the amount of
      FDR depends on the incidence on the binary scale. RIM still suffered from higher
      biases (15-100% over- or under-estimation of true values) and high standard
      errors in QTL variance and location estimates than GIM for QEI models. Hence GIM
      is recommended for disease QTL mapping with QEI. In the presence of QEI, the
      model including QEI has more power (20-80% increase) to detect the QTL when the
      average QTL effect is small (in a situation where the model with a main QTL only
      is not too powerful). Top-down model selection is proposed in which a full test
      for QEI is conducted first and then the model is subsequently simplified. Methods
      and results will be applicable to human, plant and animal QTL mapping
      experiments.

PMID- 16978429
TI  - Growth and colour development of some surface ripening bacteria with Debaryomyces
      hansenii on aseptic cheese curd.
AB  - The growth of five bacteria isolated from red-smear cheeses, Brevibacterium
      aurantiacum, Corynebacterium casei, Corynebacterium variabile, Microbacterium
      gubbeenense and Staphylococcus saprophyticus in mixed cultures with Debaryomyces
      hansenii on aseptic model cheese curd at 10 and 14 degrees C was investigated. At
      both temperatures, C. casei and Micro. gubbeenense had a longer lag phase than C.
      variabile, Brevi. aurantiacum and Staph. saprophyticus. In all cultures, lactose
      was utilised first and was consumed more rapidly at 14 degrees C than at 10
      degrees C, i.e., 6 d at 14 degrees C and 10 d at 10 degrees C. This utilisation
      coincided with the exponential growth of Deb. hansenii on the cheese surface.
      Lactate was also used as a carbon source and was totally consumed after 21 d at
      14 degrees C and approximately 90% was consumed after 21 d at 10 degrees C
      regardless of the ripening culture. Small differences (<0.5 pH unit) in the
      surface-pH during ripening were noticeable between ripening cultures. Differences
      in the colour development of the mixed cultures with the yeast control were only
      noticeable after 15 d for Brevi. aurantiacum and after 21 d for the other
      bacteria. Regardless of the organisms tested, colour development and colour
      intensity were also greater at 14 degrees C than at 10 degrees C. This study has
      provided useful information on the growth and contribution to colour development
      of these bacteria on cheese.

PMID- 16978430
TI  - Effects of ventilation rate and of dietary protein level in an intensive dairy
      sheep system on the features of Canestrato Pugliese cheese.
AB  - Effects of ventilation rate and of dietary protein level in an intensive dairy
      sheep system on the features of Canestrato Pugliese cheese were studied. Cheeses
      were manufactured from the bulk milk obtained from ewes subjected to four
      different experimental treatments: (1) low dietary crude protein (CP) of 13% in
      dry matter (DM) at a low ventilation rate (23.5 m3/h per ewe) (LPLV); (2) low
      dietary CP at a moderate ventilation rate (47 m3/h per ewe) (LPMV), (3) moderate
      dietary CP of 16% DM at a low ventilation rate (MPLV); and (4) moderate dietary
      CP dietary at a moderate ventilation rate (MPMV). Bulk milk and cheeses (at 1,
      15, 45 and 90 d of ripening) were analysed for chemical composition, N fractions
      and plasmin-plasminogen activities. The pH 4.6-soluble and insoluble N fractions
      were analysed by urea-PAGE. Bulk milk from ewes receiving the low CP diet
      displayed higher casein and lower urea contents. Ewes subjected to the low
      ventilation rate displayed a higher plasminogen activity in milk, whereas no
      differences emerged among treatments in the conversion of zymogen to plasmin.
      During ripening the plasmin-plasminogen system in cheese did not display
      significant changes across treatments. At 90 d of ripening, the cheese produced
      with milk from ewes receiving the low CP diet and exposed to the low ventilation
      rate displayed more markedly stained bands in the area of gamma-caseins in pH 4.6
      insoluble N fraction. As from 15 d of ripening, the pH 4.6-soluble fraction
      showed a greater number of bands in the LPMV and MPMV than in the LPLV and MPLV
      cheeses. The results showed that Canestrato Pugliese cheese manufactured with
      milk from ewes fed the low CP diet and exposed to the moderate ventilation rate
      was characterized by higher protein and casein content in the fresh cheese and by
      a greater proteolysis after 90 d of ripening.

PMID- 16978431
TI  - Effect of a metabolically created systemic acidosis on calcium homeostasis and
      the diurnal variation in urine pH in the non-lactating pregnant dairy cow.
AB  - Reducing the dietary cation-anion difference (DCAD) has been shown to be an
      effective means of preventing parturient paresis in confinement systems where
      cows are offered a total mixed ration containing DCAD-reducing mineral compounds
      (anionic salts). Such a supplementation strategy is not possible in cows being
      group fed forages precalving, and little is known about the effect of
      supplementing these cows with large amounts of anionic salts twice daily. Eight
      non-lactating, pregnant Holstein-Friesian cows were allocated to two levels of
      DCAD (-20 and +18 meq/100 g DM) for 24 d, with an intensive Ca balance undertaken
      in metabolism stalls following a 2-week acclimatization to diet. The basal diet
      was 3 kg DM of crushed barley and 7 kg DM of pasture-hay. Urine and faeces were
      collected separately, weighed daily for 5 d and analysed for Ca content. Urinary
      Ca, creatinine and hydroxyproline concentration and plasma Ca concentration were
      determined during the period of the balance study. The diurnal pattern in urine
      and rumen pH was determined over 2 d. Decreasing DCAD reduced (P<0.001) the pH of
      urine, and increased (P<0.05) Ca absorption. Plasma Ca concentration was not
      affected by DCAD, and DCAD did not affect the output of urinary hydroxyproline, a
      marker of bone resorption. Twice-daily supplementation of anionic salts was
      sufficient to reduce the pH of blood and increase gastrointestinal Ca absorption.
      There was no diurnal variation in the pH of urine, suggesting that time of
      sampling to determine efficacy of DCAD in reducing systemic pH was not important.

PMID- 16978432
TI  - Biological activity of bovine milk on proliferation of human intestinal cells.
AB  - To evaluate the bioactivity of bovine milk from different stages of lactation on
      human intestinal tissue, a human fetal small intestinal cell line was used as a
      model system. Milk samples representing six stages of lactation: days 1, 2-3, 6-7
      and weeks 12 and 24 after parturition, 1 week before drying off, and milk-like
      secretion from two stages of the dry period: 7 weeks and 3-4 weeks before
      expected calving, were collected from 64 Holstein Friesian cows. The whey
      fraction of the milk or milk-like secretion was added to the culture medium in
      concentrations ranging from 0.078% to 10%. The growth-promoting activity of whey
      was measured by determining the incorporation of [3H]thymidine into DNA for the
      last 24 h of the culture period. Whey fractions from all six stages of lactation
      stimulated growth of intestinal cells. The growth-promoting activity of colostrum
      or milk significantly decreased within the first week after calving. The growth
      promoting activity in mature milk increased gradually during lactation to reach a
      level significantly higher than that obtained with colostrum. The growth
      promoting activity of whey from milk-like secretion collected after drying off
      was lower than that of colostrum. Whey from different stages of lactation
      contained significantly different concentrations of TGF-beta1 (0.5-27 ng/ml) and
      TGF-beta2 (12-1219 ng/ml). However, neither the differences in TGF-beta1 and TGF
      beta2, nor the differences in IGF-I and IGF-binding proteins could fully explain
      the differences in growth-promoting activity of colostrums or milk from different
      stages of lactation, suggesting that other factors were also involved. The
      present study showed that bovine milk contained a number of biologically active
      components that affected growth and development of human intestinal tissue. The
      results showed that the growth-promoting activity of colostrum and milk was
      dependent on the stage of lactation in accordance with previous results obtained
      with mammary epithelial cells. The changes in growth-promoting activity with
      stage of lactation were probably related to changes in concentrations of several
      growth factors.

PMID- 16978433
TI  - Staphylococcus aureus and Streptococcus dysgalactiae in Norwegian herds after
      introduction of selective dry cow therapy and teat dipping.
AB  - The objective was to promote a reduction in the prevalence of Staphylococcus
      aureus and Streptococcus dysgalactiae after 2 years of selective dry cow
      therapies and teat dipping/external teat sealant implementation. Three different
      dry cow treatments, one long-acting and two short-acting penicillin-based
      products were tested at herd level together with a negative control teat dipping
      group, an iodine teat dipping group and DryFlextrade mark, an external teat
      sealant. The regimes were independently randomly allocated to 178 dairy herds.
      Yearly bacteriological quarter milk samples were collected from all cows at the
      beginning of the trial, after 1 year and 2 years. At herd level, a total of 15%
      of the herds showed no Staphylococcus aureus isolates after 2 years, compared
      with 5% at the beginning. The distribution of Streptococcus dysgalactiae infected
      herds remained the same after 2 years. At cow level, there were no significant
      differences in the reduction of Staph. aureus between the different dry cow
      therapies and teat dipping regimes. But there was a significant reduction of Str.
      dysgalactiae in the iodine teat dipping group compared with Dryflextrade mark and
      the negative control group. The proportional rate of Staph. aureus positive
      quarters was reduced from 65.9% to 54.9% after 2 years. As for Str. dysgalactiae,
      an increase was observed from 14.2% to 15.2%.

PMID- 16978434
TI  - Natural and recombinant bovine somatotropin: immunodetection with a sandwich
      ELISA.
AB  - Bovine Somatotropin (bST) is a peptide hormone secreted by the anterior pituitary
      gland and its recombinant form (rbST) is used for artificially boosting milk
      yield in cows. Identification of rbST is difficult in that there is little
      difference from the pituitary bST (pbST). In this work, we further studied the
      possibility of immunologically discriminating between rbST and pbST. With this
      purpose, we produced mouse monoclonal antibodies using, as antigen, a peptide
      mimicking the N-terminus of rbST from Monsanto (rbST-M) conjugated to keyhole
      limpet haemocyanin (KLH) and polyclonal antibodies in rabbits immunized with the
      whole bST or rbST-M. Hence, we developed a sandwich ELISA with the obtained
      antibodies for detection and quantification of bST in serum and compared its
      performance on the two worldwide commercialized rbSTs: rbST-M and rbST from LG
      Life Science (rbST-LG). The lowest detection limit of the assay was 0.05 ng/ml
      for rbST-M, 0.10 ng/ml for rbST-LG and 0.15 ng/ml for pbST. Furthermore, the
      assay showed the capability to amplify the signal in the presence of rbSTs,
      recognizing more efficiently rbST-M and rbST-LG than pbST (ECn pbST/ECn rbST: 3
      and 1.6 respectively). Its employment for measuring bST levels in sera from
      bovines administered with rbST LG allowed us to detect exceptional values due to
      the treatment itself and probably further increased as a consequence of the
      higher affinity for rbSTs of our monoclonal antibody.

PMID- 16978435
TI  - Associations between somatic cell counts at calving or prior to drying-off and
      clinical mastitis in the remaining or subsequent lactation.
AB  - Data from 350 herds enrolled in the Norwegian Dairy Herd Recording System (NDHRS)
      were used to investigate the associations between the first two cow-milk somatic
      cell counts (SCC) test-days' results after calving or the three last SCC test
      days prior to drying off in the first lactation and the hazard ratio (HR) of
      clinical mastitis (CM) during the remaining first or the subsequent second
      lactation respectively. Altogether, 9519 first lactations and 6046 second
      lactations were included. Cox regression analyses adjusted for herd frailty
      effect were used. In the first lactation, SCC>40000 cells/ml on the first or
      second test-day was significantly associated with an increased risk of a CM event
      in the remaining first lactation. HR, compared with 10000 cells/ml, increased
      from 1.6 (1.4) for SCC of 40000-60000 cells/ml to 6.9 (4.2) for SCC >800000
      cells/ml, when using the first (second) SCC test-day in the first lactation. Cows
      with a geometric mean of the three last SCC test-days between 50000 and 100000
      cells/ml and between 401000 and 800000 cells/ml in the first lactation had HR of
      CM during the second lactation of 1.3 and 2.8 respectively compared with a
      reference group of 10000-20000 cells/ml. If a CM episode in the first lactation
      occurred, the HR for having a CM event during the second lactation was 1.5. There
      was a significant frailty effect which disappeared if the incidence rate of CM at
      herd level was included in the model.

PMID- 16978436
TI  - Associations between lameness and production, feeding and milking attendance of
      Holstein cows milked with an automatic milking system.
AB  - A longitudinal study involving 73 primiparous (PP) and 47 multiparous (MP)
      Holstein cows was conducted over an 8-month period to assess the associations
      between locomotion score (LCS) and milk production, dry matter intake (DMI),
      feeding behaviour, and number of visits to an automatic milking system (AMS).
      Twice weekly, all cows were locomotion scored (scale 1-5) by the same observer.
      Individual eating behaviour and individual feed consumption at each cow visit to
      the feed troughs, individual milk production, the time of milking, and the number
      of milkings for each cow were recorded for the day of locomotion scoring and the
      day before and after. Dependent variables, such as milk yield, DMI, etc. were
      modelled using a mixed-effects model with parity, LCS, days in milk (DIM), the
      exponential of -0.05 DIM, and the interaction between parity and LCS, as fixed
      effects and random intercepts and random slopes for the linear and the
      exponential of -0.05DIM effects within cow. LCS did not affect time of attendance
      at feed troughs, but affected the location that cows occupied in the feed
      troughs. The time devoted to eating and DMI decreased with increasing LCS. Milk
      production decreased with LCS>3. The number of daily visits to the AMS also
      decreased with increasing LCS. The cows with high LCS were fetched more often
      than the cows with low LCS. Overall, PP cows were more sensitive to the effects
      of increasing LCS than were MP cows. The decrease in milk production observed
      with increasing LCS seemed to be affected similarly by the decrease in DMI and by
      the decrease in number of daily visits to the AMS. A further economic loss
      generated by lame cows with AMS will be associated with the additional labour
      needed to fetch them.

PMID- 16978437
TI  - Effects of melatonin on the yield and composition of milk from grazing dairy cows
      in New Zealand.
AB  - The aim was to determine whether administration of melatonin would alter the
      yield and composition of milk from grazing dairy cows in summer. Twelve sets of
      spring-calving identical twin Friesian cows were used in the experiment. In late
      November (late spring), one twin from each set was given slow-release melatonin
      implants behind the ears (108 mg melatonin/cow). Two further implantations
      occurred at 4-weekly intervals to maintain increased circulating concentrations
      of melatonin for 12 weeks. The other twin served as a control. Milk yield and
      composition were measured twice prior to treatment and then four times over the
      following 12 weeks. Concentrations of melatonin, prolactin and insulin-like
      growth factor 1 (IGF-1) were measured in blood plasma twice before treatment and
      then either seven (melatonin and prolactin) or three (IGF-1) further times during
      the experiment. Management procedures for all cows were similar and cows grazed a
      daily pasture allowance of approximately 30 kg DM/cow as their sole feed source.
      In melatonin-treated cows there was a decrease in mean concentrations of
      prolactin in plasma, but concentrations of IGF-1 did not change. Melatonin
      reduced milk yield by 6 weeks after treatment and by the end of the 12-week
      experimental period milk yield in melatonin-treated cows had fallen by 23%.
      Melatonin also reduced concentrations of lactose in milk, but increased
      concentrations of fat, protein and casein, changes that were broadly similar to
      those that occur in late lactation in seasonally calving dairy cows. Thus, the
      results suggest that some of the variation in the volume and quality of milk
      throughout the season in New Zealand dairy systems may be due to changes in
      photoperiod mediated by increased concentrations of plasma melatonin in
      association with decreased concentrations of plasma prolactin.

PMID- 16978438
TI  - Use and relevance of a bovine mammary gland explant model to study infection
      responses in bovine mammary tissue.
AB  - Our aim was to develop an explant model to define more precisely the early
      response of bovine mammary epithelial cells to infection. Therefore we
      investigated the mRNA expression encoding for some soluble immunological factors
      in lipopolysaccharide (LPS)-treated bovine mammary gland explants. Explants were
      taken out from the mammary gland of eight lactating cows after slaughter then
      incubated with LPS (10 mug/ml) for 6 h. The mRNA expression of alpha-lactalbumin
      (alpha-la), various cytokines, tumour necrosis factor (TNF)-alpha, interleukin
      (IL)-1beta, IL-6, IL-8, and two immunoglobulin receptors, the neonatal Fc
      receptor (FcRn) and polymeric immunoglobulin receptor (pIGR), were assessed with
      qPCR before and after 3 h and 6 h of LPS challenge. Both immunoglobulin receptors
      and alpha-la increased at 3 h then recovered their initial level at 6 h whereas
      IL-1beta, IL-6 and IL-8 increased only after 6 h (P<0.05). Surprisingly, TNF
      alpha transcripts did not show any regulation in response to the LPS treatment.
      We nevertheless concluded that our model was valid to examine the short-term
      response of mammary epithelial cell challenged with LPS.

PMID- 16978439
TI  - Getting ready for the marriage market? The association between divorce risks and
      investments in attractive body mass among married Europeans.
AB  - This article explores to what extent married middle-aged individuals in Europe
      are governed by the risk of experiencing divorce, when shaping their physical
      appearance. The main result is that divorce risks, proxied by national divorce
      rates, are negatively connected to body mass index (BMI) among married
      individuals but unrelated to BMI among singles. Hence, it seems that married
      people in societies where divorce risks are high are more inclined to invest in
      their outer appearance. One interpretation is that high divorce rates make
      married people prepare for a potential divorce and future return to the marriage
      market.

PMID- 16978440
TI  - Babesia parasites develop and are transmitted by the non-vector soft tick
      Ornithodoros moubata (Acari: Argasidae).
AB  - Ornithodoros moubata ticks were fed on blood infected with Babesia equi. However,
      the parasites were quickly cleared as evidenced by the disappearance of B. equi
      specific ribosomal RNA from the ticks. We hypothesized that if the Babesia
      parasite can escape midgut-associated barriers a non-vector tick can become
      infected with Babesia. To test this hypothesis, B. equi parasite-infected blood
      from in vitro culture was injected into the haemocoel of ticks. B. equi-specific
      rRNA was surprisingly detected 45 days after injection even in the eggs. Babesia
      free dogs were infested with O. moubata ticks that were infected by inoculation
      with B. gibsoni-infected red blood cells. Parasitaemia and antibody production
      against Bg-TRAP of B. gibsoni increased gradually. These results indicate that O.
      moubata may be a useful vector model for Babesia parasites and also a very
      important tool for studies on tick immunity against Babesia parasites and tick
      Babesia interactions.

PMID- 16978441
TI  - Eukaryotic expression of recombinant Pso o 1, an allergen from Psoroptes ovis,
      and its localization in the mite.
AB  - A cDNA encoding the immunogen Pso o 1 from Psoroptes ovis was obtained by
      polymerase chain reaction (PCR) amplification. The amplicon contained the entire
      coding sequence for the prepro-enzyme in an open reading frame (ORF) of 966 bp.
      This gene encoded a predicted protein of 322 amino acids (aa) with 64% aa
      identity (80% similarity) to the major house dust mite faecal allergen Der f 1.
      The pro-enzyme form of Pso o 1 was expressed as a recombinant protein in the
      Pichia pastoris-eukaryotic expression system. Maturation of the recombinant pro
      enzyme by autocatalytic activation was not observed, and such maturation could
      not be achieved using a number of techniques known to activate recombinant Der p
      1 and Der f 1 expressed in the same system. Serum raised against recombinant Pso
      o 1 cross-reacted with mature Der p 1 and allowed Pso o 1 to be immunolocalized
      to the gut of P. ovis.

PMID- 16978442
TI  - Risk factors for nausea and vomiting following vitrectomy in adults.
AB  - BACKGROUND AND OBJECTIVE: Postoperative nausea and vomiting (PONV) after
      ophthalmic surgery under general anaesthesia remains a complex and perturbing
      complication associated with several factors. Little information is available
      regarding the risk factors for nausea and vomiting after vitrectomy in adults. In
      this study, we evaluated the potential risk factors for PONV after vitrectomy in
      adult patients. METHODS: Univariate and multivariate analyses of clinical factors
      associated with PONV were undertaken in a retrospective case-control series of
      247 adult patients undergoing vitrectomy under general anaesthesia. We examined
      PONV for the first 48 h. Factors examined were age, body mass index (BMI),
      smoking status, H2-blocker as premedication, type of general anaesthesia
      (sevoflurane and fentanyl or total intravenous (i.v.) anaesthesia with propofol
      and fentanyl), duration of surgery, and intraoperative fentanyl dose. RESULTS:
      Fifty-nine patients (24%) reported one or more episodes of PONV during the study
      period. Female gender (P < 0.01), lower BMI (P < 0.01) and general anaesthesia
      with inhalational anaesthetics (P < 0.01) were significantly related to nausea
      during the first 2 h postoperatively. Female gender (P < 0.01) was significantly
      related to nausea and vomiting throughout the study period. Other factors,
      including smoking status, did not alter the risk for nausea and/or vomiting.
      CONCLUSIONS: We conclude that female gender, lower BMI and inhalation anaesthesia
      are the main risk factors for PONV after vitrectomy in adults. Smoking status did
      not reduce the incidence of PONV in our patients.

PMID- 16978443
TI  - Cyclic AMP response element-binding protein in post-mortem brain of teenage
      suicide victims: specific decrease in the prefrontal cortex but not the
      hippocampus.
AB  - Abnormalities in both adenylyl cyclase (AC) and phosphoinositide (PI) signalling
      systems have been observed in the post-mortem brain of suicide victims. Cyclic
      AMP response element-binding protein (CREB) is a transcription factor that is
      activated by phosphorylating enzymes such as protein kinase A (PKA) and protein
      kinase C (PKC), which suggests that both AC and PI signalling systems converge at
      the level of CREB. CREB is involved in the transcription of many neuronally
      expressed genes that have been implicated in the pathophysiology of depression
      and suicide. Since we observed abnormalities of both PKA and PKC in the post
      mortem brain of teenage suicide victims, we examined if these abnormalities are
      also associated with abnormalities of CREB, which is activated by these
      phosphorylating enzymes. We determined CRE-DNA binding using the gel shift assay,
      as well as protein expression of CREB using the Western blot technique, and the
      mRNA expression of CREB using a quantitative reverse transcriptase-polymerase
      chain reaction (RT-PCR) technique in the prefrontal cortex (PFC), and hippocampus
      obtained from 17 teenage suicide victims and 17 matched normal control subjects.
      We observed that the CRE-DNA binding and the protein expression of CREB were
      significantly decreased in the PFC of teenage suicide victims compared with
      controls. There was also a significant decrease in mRNA expression of CREB in the
      PFC of teenage suicide victims compared with control subjects. However, there
      were no significant differences in CRE-DNA binding or the protein and mRNA
      expression of CREB in the hippocampus of teenage suicide victims compared with
      control subjects. These results suggest that the abnormalities of PKA, and of
      PKC, observed in teenage suicide victims are also associated with abnormalities
      of the transcription factor CREB, and that this may also cause alterations of
      important neuronally expressed genes, and provide further support of the signal
      transduction of abnormalities in suicide.

PMID- 16978444
TI  - Anabolic androgenic steroid abuse and mood disorder: a case report.

PMID- 16978445
TI  - A comparative study of the plasma membrane permeabilization and fluidization
      induced by antipsychotic drugs in the rat brain.
AB  - We compared the potency of the interaction of three antipsychotic drugs, i.e.
      chlorpromazine (CPZ), haloperidol (Hal) and sulpiride (Sul), with the plasma
      membrane in the rat brain. CPZ loading (> or = 100 microM) dose-dependently
      increased both membrane permeability (assessed as [18F]2-fluoro-2-deoxy-D-glucose
      6-phosphate release from brain slices) and membrane fluidity (assessed as the
      reduction in the plasma membrane anisotropy of 1,6-diphenyl-1,3,5-hexatriene). On
      the other hand, a higher concentration of Hal (1 mM) was required to observe
      these effects. However, Sul failed to change membrane permeability and fluidity
      even at a high concentration (1 mM). These results indicated the following
      ranking of the potency to interact with the membrane: CPZ>Hal>Sul. The difference
      among antipsychotic drugs in the potency to interact with the plasma membrane as
      revealed in the present study may be partly responsible for the difference among
      the drugs in the probability of inducing extrapyramidal side-effects such as
      parkinsonism and tardive dyskinesia.

PMID- 16978447
TI  - Are amyloid diseases caused by protein aggregates that mimic bacterial pore
      forming toxins?
AB  - Protein fibrillization is implicated in the pathogenesis of most, if not all, age
      associated neurodegenerative diseases, but the mechanism(s) by which it triggers
      neuronal death is unknown. Reductionist in vitro studies suggest that the amyloid
      protofibril may be the toxic species and that it may amplify itself by inhibiting
      proteasome-dependent protein degradation. Although its pathogenic target has not
      been identified, the properties of the protofibril suggest that neurons could be
      killed by unregulated membrane permeabilization, possibly by a type of
      protofibril referred to here as the 'amyloid pore'. The purpose of this review is
      to summarize the existing supportive circumstantial evidence and to stimulate
      further studies designed to test the validity of this hypothesis.

PMID- 16978448
TI  - Epidemiology of parasitic protozoan infections in Soay sheep (Ovis aries L.) on
      St Kilda.
AB  - The feral Soay sheep (Ovis aries L.) population on Hirta, St Kilda, is host to a
      diverse component parasite community, but previous parasitological studies of the
      population have only focussed on the metazoan species. This paper reports the
      first epidemiological study of the protozoan species comprising Cryptosporidium
      parvum, Giardia duodenalis and 11 species of Eimeria in Soay sheep across 3 years
      of varying host population density. Prevalence and intensity of almost all
      species of protozoa significantly decreased with host age, with the exception of
      E. granulosa, which increased in prevalence with host age. The prevalence of C.
      parvum appeared to vary positively with host population density but that of G.
      duodenalis did not vary significantly with density. Most species of Eimeria
      showed a distinct lag in infection level following the host population crash of
      2002, taking up to 2 years to decrease. Mixed Eimeria species intensity and
      diversity were highest in 2002, a year of low host density. Parasite diversity
      decreased with host age and was higher in males. There were 5 positive pair-wise
      associations between protozoa species in terms of prevalence. The results of this
      study highlight the potential for protozoal infection to shape the evolution of
      parasite resistance in wild host populations harbouring diverse parasite species.

PMID- 16978446
TI  - The endophenotype concept in psychiatric genetics.
AB  - The idea that some phenotypes bear a closer relationship to the biological
      processes that give rise to psychiatric illness than diagnostic categories has
      attracted considerable interest. Much effort has been devoted to finding such
      endophenotypes, partly because it is believed that the genetic basis of
      endophenotypes will be easier to analyse than that of psychiatric disease. This
      belief depends in part on the assumption that the effect sizes of genetic loci
      contributing to endophenotypes are larger than those contributing to disease
      susceptibility, hence increasing the chance that genetic linkage and association
      tests will detect them. We examine this assumption by applying meta-analytical
      techniques to genetic association studies of endophenotypes. We find that the
      genetic effect sizes of the loci examined to date are no larger than those
      reported for other phenotypes. A review of the genetic architecture of traits in
      model organisms also provides no support for the view that the effect sizes of
      loci contributing to phenotypes closer to the biological basis of disease is any
      larger than those contributing to disease itself. While endophenotype measures
      may afford greater reliability, it should not be assumed that they will also
      demonstrate simpler genetic architecture.

PMID- 16978449
TI  - Clonal propagation and the fast generation of karyotype diversity: An in vitro
      Leishmania model.
AB  - In the present work we studied the karyotype stability during long-term in vitro
      maintenance in 3 cloned strains of Leishmania (Viannia) peruviana, Leishmania
      (Viannia) braziliensis and a hybrid between both species. Only the L. (V.)
      peruviana strain showed an unstable karyotype, even after subcloning. Four
      chromosomes were studied in detail, each of them characterized by homologous
      chromosomes of different size (heteromorphy). Variations in chromosome patterns
      during in vitro maintenance were rapid and discrete, involving loss of
      heteromorphy or appearance of additional chromosome size variants. The resulting
      pattern was not the same according to experimental conditions (subinoculation
      rate or incubation temperature), and interestingly, this was associated with
      differences in growth behaviour of the respective parasites. No change in total
      ploidy of the cells was observed by flow cytometry. We discuss several mechanisms
      that might account for this variation of chromosome patterns, but we favour the
      occurrence of aneuploidy, caused by aberrant chromosome segregation during
      mitosis. Our results provide insight into the generation of karyotype diversity
      in natural conditions and highlight the relativity of the clone concept in
      parasitology.

PMID- 16978450
TI  - High polymorphism in Plasmodium vivax merozoite surface protein-5 (MSP5).
AB  - A key issue relating to developing multi-component anti-malarial vaccines, lies
      in studying Plasmodium vivax surface proteins' genetic variation. The present
      work was aimed at amplifying, cloning and sequencing the gene encoding P. vivax
      merozoite surface protein 5 (PvMSP5) in samples obtained from infected patients
      from Colombian areas having varying malaria transmission rates. Nucleotide
      sequence data reported in this paper are available in the GenBank, EMBL and DDBJ
      databases under Accessions numbers DQ341586 to DQ341601. Our results have
      revealed that PvMSP5 is one of the P. vivax surface proteins having greater
      polymorphism, this being restricted to specific protein regions. The intron and
      exon II (which includes the GPI anchor and EGF-like domain) were both highly
      conserved when compared to exon I; exon I displayed the greatest variation and
      most of the recombination events occurred within it. No geographical grouping was
      observed. The Nei-Gojobori test revealed significant positive selection in the
      samples analysed here, whereas Tajima and Fu and Li tests presented a neutral
      selection pattern. The results reflected a localized variation pattern,
      recombination between PvMSP5 alleles and also functional and immune pressures,
      where stronger selective forces might be acting on exon I than on exon II,
      suggesting that the latter could be an important region to be included in an anti
      malarial vaccine.

PMID- 16978451
TI  - Parasite genetic diversity does not influence TNF-mediated effects on the
      virulence of primary rodent malaria infections.
AB  - The pro-inflammatory cytokine tumour necrosis factor alpha (TNF-alpha) is
      associated with malaria virulence (disease severity) in both rodents and humans.
      We are interested in whether parasite genetic diversity influences TNF-mediated
      effects on malaria virulence. Here, primary infections with genetically distinct
      Plasmodium chabaudi chabaudi (P.c.c.) clones varied in the virulence and cytokine
      responses induced in female C57BL/6 mice. Even when parasitaemia was controlled
      for, a greater day 7 TNF-alpha response was induced by infection with more
      virulent P.c.c. clones. Since many functions of TNF-alpha are exerted through TNF
      receptor 1 (TNFR1), a TNFR-1 fusion protein (TNFR-Ig) was used to investigate
      whether TNFR1 blockade eliminated clone virulence differences. We found that TNFR
      1 blockade ameliorated the weight loss but not the anaemia induced by malaria
      infection, regardless of P.c.c. clone. We show that distinct P.c.c. infections
      induced significantly different plasma interferon gamma (IFN-gamma), interleukin
      6 (IL-6) and interleukin 10 (IL-10) levels. Our results demonstrate that
      regardless of P.c.c. genotype, blocking TNFR1 signalling protected against weight
      loss, but had negligible effects on both anaemia and asexual parasite kinetics.
      Thus, during P.c.c. infection, TNF-alpha is a key mediator of weight loss,
      independent of parasite load and across parasite genotypes.

PMID- 16978453
TI  - Subclinical mastitis in dairy cows in Swiss organic and conventional production
      systems.
AB  - The objective was to compare the prevalence of subclinical mastitis (SM) and of
      udder pathogens in 60 Swiss organic (OP) and 60 conventional production systems
      (CP). Cows (n=970) were studied for SM prevalence and udder pathogens at median
      31 d and 102 d post partum. Cows showing a >or=1+ positive California Mastitis
      Test (CMT) in at least one quarter were considered to have SM. Cow-level
      prevalences of SM for visits at 31 d and 102 d post partum (39% and 40% in OP and
      34% and 35% in CP) were similar, but quarter-level prevalences of SM were higher
      (P<0.02) in OP than CP (15% and 18% in OP and 12% and 15% in CP). Median somatic
      cell counts in milk at 31 d post partum were higher (P<0.05) in OP than CP cows
      (43000 and 28000 cells/ml, respectively), but were similar at 102 d post partum
      in OP and CP cows (45000 and 38000 cells/ml, respectively). In milk samples from
      quarters showing a CMT reaction >or=2+ the prevalences of coagulase negative
      staphylococci were lower (P<0.05) at 102 d post partum, whereas prevalences of
      non-agalactiae streptococci were higher (P<0.05) in OP than in CP cows at 31 d
      and 102 d post partum. In conclusion, under Swiss conditions, subclinical
      mastitis is a greater problem in organic than in conventional production systems,
      but differences are not marked.

PMID- 16978452
TI  - Characterization of cardiopulmonary function and cardiac muscarinic and
      adrenergic receptor density adaptation in C57BL/6 mice with chronic Trypanosoma
      cruzi infection.
AB  - Circulating antibodies in chagasic patients interact with myocardial beta
      adrenergic and muscarinic cholinergic receptors, triggering intracellular signals
      that alter cardiac function along the course of the disease. However, until now,
      experimental data in models of chronically infected chagasic mice linking the
      effects on myocardial beta adrenergic and muscarinic receptors to cardiopulmonary
      dysfunction is lacking. Thus, we studied C57BL/6 mice 8 months after
      intraperitoneal injection of 100 trypomastigote forms of the Colombian strain of
      T. cruzi. Uninfected mice, matched in age, were used as controls.
      Histopathological analyses (inflammation and fibrosis) and radio-ligand binding
      assays for estimation of muscarinic and adrenergic receptor density were
      performed in myocardium tissue samples. When compared to controls, infected mice
      had electrical conduction disturbances, diastolic dysfunction, lower O2
      consumption and anaerobic threshold. In addition, hearts of chronic chagasic mice
      had intense inflammation and fibrosis, and decreased beta adrenergic and
      increased muscarinic receptor densities than normal controls. Our data suggest
      that chronic T. cruzi infection causes alterations in cardiac receptor density
      and fibrosis deposition which can be associated with cardiac conduction
      abnormalities, diastolic dysfunction and lower exercise capacity, associating for
      the first time all these functional and histopathological alterations in chagasic
      mice.

PMID- 16978454
TI  - Identification of a single nucleotide polymorphism at intron 16 of the caprine
      acyl-coenzyme A: diacylglycerol acyltransferase 1 (DGAT1) gene.
AB  - The DGAT1 gene encodes a microsomal enzyme that catalyses the only committed step
      in triacylglycerol synthesis by joining diacylglycerol and fatty acyl coenzyme A.
      In cattle, a K232A substitution in the DGAT1 molecule has a significant effect on
      enzyme activity and milk fat content. The prominent role of this gene in lipid
      metabolism led us to undertake the structural characterization of DGAT1 in goats.
      In this way, we have sequenced a 1552 bp fragment of the goat DGAT1 cDNA, which
      encompasses most of the coding sequence (from exon 1 to 17), and a genomic
      fragment covering exons 12 to 17. Multiple alignment of the goat DGAT1 sequences
      revealed the existence of a single nucleotide polymorphism (SNP) involving a T to
      C substitution at intron 16. We optimized a primer extension based genotyping
      method that allowed us to determine that the C variant is a minority allele with
      frequencies ranging from 0.062 (Murciano-Granadina) to 0.109 (Malaguena). This
      SNP, although not expected to have any functional effect, might be useful as a
      genetic marker in association studies to detect additional DGAT1 polymorphisms
      which might influence fat milk content and other traits of economic interest.

PMID- 16978455
TI  - Congenital oro-motor disorders.

PMID- 16978456
TI  - Synergistic muscle activation during maximum voluntary activation in children
      with or without spastic CP.

PMID- 16978457
TI  - Synergistic muscle activation during maximum voluntary contractions in children
      with and without spastic cerebral palsy.
AB  - We examined muscle recruitment patterns in children with cerebral palsy (CP) and
      comparison children without CP under conditions of maximum voluntary
      contractions. Three groups of children participated in the study: (1) 12 children
      with diplegic CP (eight males, four females; age range 4-10 y, mean age 7 y [SD 2
      y 4 mo]); (2) six children with hemiplegic CP (four males, two females; age range
      5-10 y, mean age 7 y 4 mo [SD 2 y]); and (3) 13 comparison children with normal
      motor function (seven males, six females; age range 4-11 y, mean age 7 y 2 mo,
      [SD 2 y]). The children with CP were classified according to the Gross Motor
      Function Classification System: eight were Level I, five were Level II, four were
      Level III, and one was Level IV. Surface electromyography was recorded from four
      proximal and distal lower extremity (LE) muscles. Children with CP more
      frequently activated a muscle other than the intended prime mover first, compared
      with the comparison children, especially when the prime mover was a distal
      muscle. For example, during ankle plantar flexion, when the lateral gastrocnemius
      muscle was the prime mover, children with hemiplegia showed preactivation of the
      tibialis anterior muscle and children with diplegia showed medial hamstring
      coactivation. In conclusion, children with CP showed considerable differences to
      the comparison children in how LE muscles were voluntarily activated. Greater
      understanding of muscle recruitment patterns under a variety of tasks may provide
      new directions for motor control retraining or other forms of intervention.

PMID- 16978458
TI  - Comparing functional profiles of children with hemiplegic and diplegic cerebral
      palsy in GMFCS Levels I and II: Are separate classifications needed?
AB  - The goal was to compare children with hemiplegia with those with diplegia within
      Gross Motor Functional Classification System (GMFCS) levels using multiple
      validated outcome tools. Specifically, we proposed that children with hemiplegia
      would have better gait and gross motor function within levels while upper
      extremity function would be poorer. Data were collected on 422 ambulatory
      children with cerebral palsy: 261 with diplegia and 161 with hemiplegia, across
      seven centers. Those with hemiplegia in each level performed significantly and
      consistently better on gait or lower extremity function and poorer on upper
      extremity and school function than those with diplegia. In GMFCS Level II, the
      group with hemiplegia walked faster (p = 0.017), scored 6.6 points higher on
      Dimension E of the Gross Motor Function Measure (p = 0.017), 6.7 points lower on
      Upper Extremity subscale of the Pediatric Outcomes Data Collection Instrument,
      and 9.1 points lower on WeeFIM self-care (p = 0.002). Basing motor prognosis on
      GMFCS level alone may underestimate lower extremity skills of children with
      hemiplegia, and overestimate those of children with diplegia.

PMID- 16978459
TI  - Initial development and validation of the Caregiver Priorities and Child Health
      Index of Life with Disabilities (CPCHILD).
AB  - This paper reports the development and validation of a disease-specific measure
      of health status and well-being of children with severe cerebral palsy (CP). The
      Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD)
      was constructed from recommendations from caregivers, healthcare providers, and
      review of other measures. Items spanning six domains are rated on an ordinal
      scale. Standardized scores (0-100) are reported for each domain and in total.
      Primary caregivers (n = 77) of 45 males and 32 females between 5 and 18 years of
      age (mean age 13 y 5 mo [SD 3 y 4 mo]) with CP, categorized by the Gross Motor
      Function Classification System (GMFCS) level, completed the CPCHILD. Caregivers
      of children with severe CP (GMFCS Levels IV and V) also completed a second
      administration of the CPCHILD 2 weeks after the first. The mean CPCHILD score for
      children with severe CP was 56.2 (SD 15.7; range 24-93). The mean CPCHILD scores
      for children in GMFCS Levels I to V were 22.0, 38.2, 23.0, 44.5, and 59.3
      respectively (p < 0.001). Reliability was tested in 41/52 caregivers who reported
      no change in health status between the two administrations of the CPCHILD. The
      intraclass correlation coefficient was 0.94 (95% confidence interval 0.90-0.97).
      The CPCHILD seems to be a reliable and valid measure of caregivers' perspectives
      on the health status, functional limitations, and well-being of these children.

PMID- 16978460
TI  - Influence of equinus treatments on the vertical displacement of the body's centre
      of mass in children with cerebral palsy.
AB  - We assessed the influence of equinus gait treatments on the vertical displacement
      of the body's centre of mass (COM) in 21 patients with cerebral palsy (14 males,
      7 females; mean age 8 y 9 mo [SD 2 y]; range 3 y 7 mo-17 y) presenting different
      topographical types (quadriplegia, n = 1; diplegia, n = 6; right hemiplegia, n =
      6; and left hemiplegia, n = 8). Vertical COM displacement was computed from
      ground reaction forces, and lower limb kinematics was recorded simultaneously.
      Equinus gait was treated with non-operative treatments (i.e. botulinum toxin
      injections and stretching casts) in 14 patients, and with operative treatments in
      seven patients. After non-operative treatments, the entire ankle displacement
      shifted towards dorsiflexion throughout the gait cycle, but the amplitude of the
      third foot rocker (TR) and vertical COM displacement remained unchanged. However,
      after operative treatments, the amplitude of TR increased and vertical COM
      displacement decreased. A negative linear correlation was found between the
      former variables in all the patients where 53% of the changes in their vertical
      COM displacement, after equinus gait treatments, were explained by the changes in
      TR amplitude. In fact, TR remains a main gait determinant, reducing the vertical
      COM displacement after equinus gait treatment and influencing the general gait
      pattern.

PMID- 16978461
TI  - Gait function in newly diagnosed children with autism: Cerebellar and basal
      ganglia related motor disorder.
AB  - We investigated gait in newly diagnosed children with autism. From our previous
      study with 6- to 14-year-olds, we hypothesized that motor symptoms indicative of
      basal ganglia and cerebellar dysfunction would appear across the developmental
      trajectory of autism. Two groups were recruited: children with autism (eight
      males, three females; mean age 5 y 10 mo [SD 9 mo]; range 4 y 4 mo-6 y 9 mo) and
      a comparison group of typically developing children (eight males, three females;
      mean age 5 y 9 mo [SD 1 y 1 mo]; range 4 y 3 mo-7 y 2 mo). The GAITRite Walkway
      was used to gather data from average gait and intra-walk measurements.
      Experienced physiotherapists analyzed gait qualitatively. Groups were matched
      according to age, height, weight, and IQ; although not statistically significant,
      IQ was lower in the group with autism. Spatiotemporal gait data for children with
      autism were compatible with findings from patients with cerebellar ataxia:
      specifically, greater difficulty walking along a straight line, and the
      coexistence of variable stride length and duration. Children with autism were
      also less coordinated and rated as more variable and inconsistent (i.e. reduced
      smoothness) relative to the comparison group. Postural abnormalities in the head
      and trunk suggest additional involvement of the fronto-striatal basal ganglia
      region. Abnormal gait features are stable across key developmental periods and
      are, therefore, promising for use in clinical screening for autism.

PMID- 16978462
TI  - Ethnic differences in achievement of developmental milestones by 9 months of age:
      The Millennium Cohort Study.
AB  - This paper examines ethnic differences in the attainment of developmental
      milestones during infancy and possible explanations for observed differences are
      investigated. Data from the first survey of the Millennium Cohort Study (n =
      15,994; 8212 males, 7782 females; mean age 9.2 mo [SD 0.5]) were examined. We
      found that Black Caribbean (odds ratio [OR] = 0.23, 95% confidence interval [CI]
      = 0.11-0.48), Black African (OR 0.31, 95% CI 0.18-0.55), and Indian (OR 0.55, 95%
      CI 0.33-0.93) infants were less likely to show delay in the attainment of gross
      motor milestones compared with White infants after adjustment for a range of
      explanatory variables. Pakistani and Bangladeshi infants were more likely to have
      delays in fine motor development (OR 1.69, 95% CI 1.21-2.35 and OR 2.17, 95% CI
      1.17-4.02 respectively) and communicative gestures (OR 4.19, 95% CI 1.47-11.94
      and OR 7.64, 95% CI 3.96-14.76 respectively), but these differences were
      explained by socioeconomic factors and markers of cultural tradition. In
      conclusion, unexplained ethnic differences were seen in the attainment of gross
      motor milestones, with Indian, Black Caribbean, and Black African children less
      likely to be delayed (in adjusted models). Increased likelihood of fine motor and
      communicative gesture delays among Pakistani and Bangladeshi infants, that
      disappear when socioeconomic factors are taken into account, point to the need to
      address deprivation among these groups to reduce the likelihood of developmental
      delay and possible longer term behavioural and cognitive problems and consequent
      opportunities throughout life.

PMID- 16978463
TI  - Developmental dissociation, deviance, and delay: Occurrence of attention-deficit
      hyperactivity disorder in individuals with and without borderline-to-mild
      intellectual disability.
AB  - A neurodevelopmental model for understanding the spectrum of developmental
      disabilities postulates that developmental delay, dissociation, and deviance
      reflect underlying central nervous system dysfunction. In this study, we
      determined the occurrence of the dissociated and developmentally deviant
      behavioral profile of attention-deficit-hyperactivity disorder (ADHD) among
      children with and without developmental cognitive delays (borderline-to-mild
      intellectual disability) in a population-based birth cohort (n = 5718). Among the
      70 children identified to have borderline-to-mild intellectual disability, 30% (n
      = 21; 7 females, 14 males) met research criteria for ADHD, compared to only 6.4%
      of children without intellectual disability (n = 358; 88 females, 270 males). The
      odds ratio for comorbid ADHD for children with versus without borderline-to-mild
      intellectual disability was 6.3 (95% confidence interval: 3.7-10.6; p < 0.001).
      These data illustrate that developmental dissociation and/or deviance, as
      represented by ADHD, are more likely to occur in the context of developmental
      delay, represented by borderline-to-mild intellectual disability.

PMID- 16978464
TI  - Vision in children with hydrocephalus.
AB  - Hydrocephalus in children has many aetiologies, and can cause multiple ophthalmic
      and visual disorders. This study sets out to detect and quantify visual and
      visuoperceptual dysfunction in children who have received surgical treatment for
      hydrocephalus with and without myelomeningocele, and to relate the results to the
      associated diagnoses and results from a comparison group. Seventy-five school
      aged children (41 males, 34 females) with surgically-treated hydrocephalus and
      140 comparison children (76 males, 64 females) matched for age and sex underwent
      comprehensive ophthalmologic examination. Median age at examination was 9 years
      and 4 months (range 7 y 4 mo-12 y 10 mo). Visual function deficits were
      identified in 83% (62/75) of the children with hydrocephalus. Visual impairment
      (binocular visual acuity <0.3) was found in 15% (11/73; comparison group 0%) but
      in none with myelomeningocele. Strabismus was found in 69% (51/74; comparison
      group 4% [5/140], p < 0.001), and refractive errors were found in 67% (47/70;
      comparison group 20% [28/140], p < 0.001). Cognitive visual dysfunction was
      identified in 59% (38/64; comparison group 3% [4/140], p < 0.001). These
      disorders were identified in various combinations and comprised impaired ability
      to plan movement through depth (e.g. going down a stair), impaired simultaneous
      perception, impaired perception of movement, impaired orientation, and (least
      frequently) impaired recognition. In this study, children with hydrocephalus
      associated with myelomeningocele were least commonly affected. Visual disorders
      were most frequent in those with epilepsy, cerebral palsy, and/or cognitive
      disability.

PMID- 16978465
TI  - Lower motor neuron involvement in perisylvian polymicrogyria.
AB  - Congenital bilateral perisylvian polymicrogyria syndrome (CBPS) has a cerebral
      cortical localization and its phenotype was thought to be purely central. This
      study of seven children with CBPS (five males, two females; mean age 5 y [SD 3 y
      6 mo]; range 1 mo-11 y 10 mo) documents electrophysiological evidence of lower
      motor neuron involvement in association with congenital contractures (limb or
      jaw) in six of the seven children studied. This is not an expected association
      and does not conform to the traditional lesional classification system of the
      cerebral palsies. Possible pathogenic mechanisms are discussed but this
      association of upper and lower motor neuron involvement is likely to be a
      previously unsuspected part of a genetic or other pathogenic sequence.

PMID- 16978466
TI  - Magnetic resonance spectroscopic characteristics of glutaric aciduria type II.
AB  - Magnetic resonance spectroscopy (MRS) of a 12-year-old female patient with
      glutaric aciduria type II was compared with data obtained from four healthy age-
      and sex-matched volunteers. In the clinically active phase, conventional magnetic
      resonance imaging showed mild ventricular dilatation. Frontal lobe
      choline/creatine (Cho/Cr) ratio (1.98) was higher than the ratios reported for
      the comparison participants (1.64 [SD 0.21]). The N-acetylaspartate/creatine
      (NAA/Cr) ratio (1.95) was lower than normal limits (2.66 [SD 0.23]). After
      successful riboflavin treatment and dietary restriction for proteins, the NAA/Cr
      ratio was within the normal range (2.44) and Cho/Cr ratio was below the normal
      range (1.15), suggesting riboflavin-responsive multiple acyl-coA dehydrogenase
      deficiency. An elevated Cho/Cr ratio and decreased NAA/Cr ratio is consistent
      with a demyelinating process in the active phase of glutaric aciduria type II.
      MRS helps to monitor the progress of the disease and the efficacy of treatment by
      revealing changes in NAA/Cr and Cho/Cr ratios.

PMID- 16978467
TI  - Unilateral reverse ocular bobbing caused by tuberous sclerosis.
AB  - A female aged 12 months with developmental delay and left-sided reverse ocular
      bobbing (rapid deviation of the eye upward and a slow return to the horizontal
      position) was observed. At birth, an upper left gingival mass, pathologically
      diagnosed as a benign granular cell tumour, was removed. On computed tomography
      (CT), left middle cerebral pedincular and midpontine lesions were seen. Magnetic
      resonance imaging revealed additional white matter hamartomas, corticosubcortical
      tubers, and subependymal nodules. The patient was re-examined at 36 months. Her
      general developmental quotient was equivalent to 23 months of age. Third cranial
      nerve functions and auditory brainstem response were normal. Her abnormal eye
      movements were still present. Reverse bobbing is usually observed in patients who
      are unconscious and who have significant pontine pathology and disruption of the
      reticular formation. This case is the first tuberous sclerosis-related ocular
      bobbing case to our knowledge and is interesting as the causative lesion was
      relatively mild, and ocular horizontal movements were preserved.

PMID- 16978468
TI  - The effectiveness of passive stretching in children with cerebral palsy.
AB  - Passive stretching is widely used for individuals with spasticity in a belief
      that tightness or contracture of soft tissues can be corrected and lengthened.
      Evidence for the efficacy of passive stretching on individuals with spasticity is
      limited. The aim of this review was to evaluate the evidence on the effectiveness
      of passive stretching in children with spastic cerebral palsy. Seven studies were
      selected according to the selection criteria and scored against the Physiotherapy
      Evidence Database scale. Effect size and 95% confidence intervals were calculated
      for comparison. There was limited evidence that manual stretching can increase
      range of movements, reduce spasticity, or improve walking efficiency in children
      with spasticity. It appeared that sustained stretching of longer duration was
      preferable to improve range of movements and to reduce spasticity of muscles
      around the targeted joints. Methods of passive stretching were varied. Further
      research is required given the present lack of knowledge about treatment outcomes
      and the wide use of this treatment modality.

PMID- 16978469
TI  - How should physicians manage patients with Duchenne muscular dystrophy when
      experts' recommendations are not unanimous?

PMID- 16978470
TI  - Management of cardiac involvement in neuromuscular disorders.

PMID- 16978471
TI  - [Study of foveae dorsales of nymphs and adults of four species of ticks (Acari:
      Ixodidae) by scanning electron microscopy].
AB  - The foveae dorsalis, the external opening of the sex pheromone 2,6-dichlorophenol
      producer gland, of Amblyomma cajennense, Dermacentor nitens, Rhipicephalus
      (Boophilus) microplus and Rhipicephalus sanguineus was studied with scanning
      electron microscopy. At least three specimens from each stage: unfed larvae,
      nymphs, females and males, and females fed for 4 to 6 days were examined. The
      foveae dorsales were not observed in larvae and R. (B.) microplus males. The
      foveae dorsales were observed as paired depressions, below the scutum in nymphs
      and females. In males they appeared as paired subtle elevations, located (2/3) of
      the way along the idiosoma. Generally the larger structures with a higher number
      of pores were observed in A. cajennense. Males and nymphs showed foveae dorsales
      of similar sizes but smaller than those of females. After feeding, secretions
      were observed in D. nitens and A. cajennense foveae dorsalis. In R. sanguineus
      and R. (B.) microplus this kind of secretion was not observed. An attempt to
      connect the appearance of foveae dorsalis with the role of 2,6-dichlorophenol in
      tick copula has been made. The occurrence of D. nitens females with three foveae
      dorsales was described.

PMID- 16978472
TI  - Performance of two Bm86 antigen vaccin formulation against tick using crossbreed
      bovines in stall test.
AB  - Cattle tick control remains a serious problem for cattle farms in Brazil due to
      the limited success achieved with chemicals. In Brazil, the use of vaccines for
      tick control associated with the use of chemicals and pasture rotation may open
      possibilities for integrated control. However, it is important to know whether
      regional Boophilus microplus strains are sensitive to antibodies produced by the
      available antigens: antigen preparations GavacTM and TickGard(PLUS). The aim of
      this research was to evaluate the performance of two Bm86 antigen vaccine
      formulation against tick using crossbred bovines in stall test antigen against a
      regional B. microplus strain. The experiment was carried out in central Brazil
      (20 degrees 27'S, 54 degrees 37'W). A trial was conducted in stall conditions on
      crossbred cattle under controlled infestation. Two groups of 16 animals each,
      homogeneous in weight and sex, were vaccinated with GavacTM or TickGard(PLUS),
      two groups of eight animals as control. Challenge was performed on three
      alternate days, with 5,000 larvae each time, beginning 21 days after the second
      injection. The antibody response was measured by ELISA and vaccinated animals
      presented immune response considering IgG levels. The results showed 49.2% and
      46.4% protection efficacy for GavacTM and TickGard(PLUS), respectively.

PMID- 16978473
TI  - [Distribution of anti-Neospora caninum antibodies in dairy cows at municipalities
      of Resende and Rio Claro in the State of Rio de Janeiro, Brazil].
AB  - This study aimed to verify the prevalence of anti-Neospora caninum antibodies in
      dairy cows from municipalities of Resende and Rio Claro, both located at
      sulfluminense dairy belt. A total of 29 farms from Resende and 28 from Rio Claro
      were randomly selected. To evaluate the association between herds and animals
      against the etiological agent chi2 tests were used. Seventy eight animals at
      Resende (25.74%, confidence intervals(IC) at 95%: 15.7-25.8%) had anti-N. caninum
      antibodies, while 53 animals (20.38%, IC 21-31.1%) at Rio Claro (p=0.16). No
      association between positive animals in relationship to municipalities was
      observed. When considered properties, 26 (89.7%, IC: 76, 3-94.9%) at Resende and
      24 (85.71%, IC: 67.3-96%) at Rio Claro had at least a positive animal. This
      demonstrated that anti-N. caninum antibodies were observed among dairy cows at
      both municipalities. In spite of abortions were observed with relative frequency
      in endemic areas of N. caninum, they were not observed in the present study.

PMID- 16978474
TI  - [Prevalence of antibodies anti-Neospora caninum in bovines from Anapolis and
      Goiania microregions, Goias, Brazil].
AB  - The prevalence of antibodies anti-Neospora caninum in bovines was determined in
      21 farms from Anapolis and Goiania microregions, in Goias, Brazil. Out of these
      11 were dairy farms (Holstein and crossbred Holstein-Zebu), nine had beef cattle
      (Nelore) and one was for mixed exploitation (Simental). Blood samples were
      collected from 930 animals, and sera obtained were separated and stored at -20
      degrees C. Serum samples were examined by the immunofluorescent antibody
      technique (IFAT), using tachyzoites of the NC-1 Neospora caninum strain as
      antigen. Antibodies anti-N. caninum were found in 283 (30.4%) of the 930 blood
      samples examined. All the farms were positive, with prevalence for N. caninum
      varying from 10.3% to 89.7% of the examined animals. The prevalence for beef
      herds was 29.6% (10.3% to 89.7%), for dairy herds 30.4% (14.5% to 83.3%), and for
      the mixed herd, the prevalence was 43.3%. No statistically significant
      differences were found among prevalence in animals from beef, dairy or mixed
      herds. Results confirmed that N. caninum is widespread in different types of
      bovine herds in the micro regions of Anapolis and Goiania.

PMID- 16978475
TI  - [Effects of parasitism on gill structure of Leporinus macrocephalus Garavello and
      Britsk, 1988 (Anastomidae) and Piaractus mesopotamicus Holmberg, 1887
      (Osteichthyes:Characidae)].
AB  - This work described the lesions caused in different species of fish by gill
      parasites from fee-fishing at Guariba, State of Sao Paulo. The research was
      developed from april, 1997 to march to 1999, seeking to verified the kind tissues
      lesions from fish. Of these, forty and seven were Leporinus macrocephalus and
      fifty and five Piaractus mesopotamicus. About 87.2% of the L. macrocephalus, and
      58.1% of the P. mesopotamicus were sponged by several species of parasites. The
      parasite most abundant in L. macrocephalus was Piscinoodinium pillulare, while
      monogenean, Trichodina sp and myxosporidian infected P. mesopotamicus. Severe
      gill lesions have been observed in L. macrocephalus and P. mesopotamicus caused
      by monogenean, P. pillulare e Trichodina sp. parasitism, such as intersticial
      hemorrhage, sub-epithelium edema, inflammation, epitelial hiperplasy in filaments
      and lamina, proliferation of mucosal cells and laminar fusion.

PMID- 16978476
TI  - Parasitism influence on the hepato, splenosomatic and weight/length relation and
      relative condition factor of Prochilodus lineatus (Valenciennes, 1836)
      (Prochilodontidae) of the Upper Parana River floodplain, Brazil.
AB  - One hundred and forty-nine specimens of Prochilodus lineatus (Valenciennes, 1836)
      were collected on the Upper Parana River floodplain (Brazil) from February 2000
      to June 2001. Both parasitized and unparasitized fish showed alometric growth.
      The parasitized fish presented relative condition factor (Kn) values that were
      significantly higher than those of the unparasitized fish. In the age classes
      with unparasitized fish, the mean relative condition factor was always lower.
      Starting from two years of age, the Kn values were higher in the parasitized
      hosts. The monogenean Rhinonastes pseudocapsaloideum, the copepod Gamispatulus
      sp. and the digenean Saccocoelioides magnorchis presented significant positive
      correlation between their abundance and the relative condition factor of the
      host. No species presented correlation between abundance and the hepatosomatic
      relation. The acanthocephalan Neoechinorhynchus curemai presented positive
      correlation and the metacercariae Tylodelphys sp. presented negative correlation
      between the splenosomatic relation and abundance of parasitism.

PMID- 16978477
TI  - [The occurrence of dioctophymosis in dogs from Municipality of Cachoeiro do
      Itapemirim in the State of Espirito Santo, Brazil, from May to December of 2004].
AB  - Dioctophyma renale is frequently observed in dogs from rural areas. From a total
      of 67 necropsies carried out from May to December of 2004, 56 were dogs, which
      came from the minicipality of Cachoeiro do Itapemirim, two animals parasited for
      D. renale. In one of these animals in a mass of epiplon a nematode female of 15
      cm of length was found in ectopic position. The right kidney was atrophic and
      with the presence of 2 females (58 and 50 cm) and 2 males (21 cm each). In the
      second animal, the kidneys were morphologically different. The left kidney was
      presented hypertrophic, while right kidney was observed a female with 45 cm. The
      recovered helminths were identified and fixed in AFA. During the ovariectomy of a
      dog of the same region a male nematode of approximately 20 cm was found in site
      the abdominal cavity. All of them were identified as D. renale.

PMID- 16978478
TI  - [First report of Anaplasma bovis (Donatien and Lestoquard, 1936) Dumler et al.
      (2001) at micro region of Campos dos Goytacazes, State of Rio de Janeiro,
      Brazil].
AB  - The first report of Anaplasma bovis was pointed out at the micro region of Campos
      dos Goytacazes, State of Rio de Janeiro, Brazil. Blood smears were done from
      peripherical blood vessels from 151 calves. Five calves (3.31%) were positive for
      A. bovis. Symptoms were characterized by debility, fever, pale mucous membranes,
      and enlargement of prescapular lymph nodes.

PMID- 16978479
TI  - [Cellular types involved in the immune response of females engorged of Boophilus
      microplus inoculated with Metarhizium anisopliae and Penicillium sp.].
AB  - Engorged females of Boophilus microplus were inoculated with conidia of the fungi
      Metarhizium anisopliae or Penicillium sp. Two bioassays constituted of six
      treatment groups were performed to determine the cells involved in the B.
      microplus immune response. In the first bioassay there were three different
      groups: a) engorged females inoculated with Penicillium sp. (1.36 x 108
      conidia/ml); b) engorged females inoculated with Tween 80 at 0.01% water
      solution; c) testimony group (engorged females non inoculated). Each treatment
      group was composed by ten ticks. The second bioassay was conducted following the
      same methodology described above, however, engorged females were inoculated with
      M. anisopliae (1.24 x 108 conidia/ml). Ticks were inoculated with 1 microl of
      fungus suspension or Tween 80 solution directly in the idiosoma. The haemolymph
      of each tick was collected 24.48 and 72 hours post-challenge. In all groups were
      observed prohemocytes, plasmatocytes, granulocytes and spherulocytes.
      Adipohemocytes were identified in small number only in ticks non inoculated
      (testimony group). Oenocytoids were found in ticks inoculated with M. anisopliae
      and ticks non inoculated of both bioassays. In the first bioassay, ticks treated
      with Penicillium sp. presented conidial phagocytosis by granulocytes and
      plasmatocytes. In the second bioassay, ticks did not overcome the infection
      resulting in death 72 hours after post challange.

PMID- 16978481
TI  - The burden of debt for Canadian dental students: part 1. Review of the
      literature.
AB  - Debt among Canadian university graduates is increasing, while money apportioned
      to federal and provincial needs-based student assistance programs has been
      decreasing since the 1990s. Dental students have had to absorb increased tuition
      fees at both the undergraduate and post-baccalaureate levels. Existing debt and
      high tuition fees may adversely influence a potential candidate"s decision to
      enroll in dental school. Likewise, debt incurred during the minimum 2 years of
      pre-dental education adds to the future debt load of dental graduates. It seems
      that few dental students can remain debt-free during their dental education,
      although data are lacking about the extent of debt among dental students and its
      impact on their career decisions. Government statistics focus primarily on
      tuition costs for baccalaureate-degree students. Tuition and clinic-related fees
      constitute a significant proportion of costs for dental students; moreover,
      university administrations perceive dentistry as an expensive curriculum. This
      first article of a 4-part series examines debt among dental students, both
      nationally and internationally.

PMID- 16978482
TI  - Antibacterial activity of a new endodontic sealer against Enterococcus faecalis.
AB  - AIM: The purpose of this study was to test a new root canal sealer (Epiphany) and
      5 other root canal sealers (Diaket, Endomethasone, AH 26, Sealapex, Sultan) for
      their antimicrobial effect on Enterococcus faecalis. MATERIALS AND METHODS: The
      antimicrobial effect of 6 root canal sealers was tested by the agar diffusion
      method. The freshly mixed sealers were placed in prepared wells of agar plates
      inoculated with E. faecalis. All plates were incubated for 72 hours at 37 degrees
      C under aerobic conditions, and zones of inhibition were measured at 24, 48 and
      72 hours. RESULTS: All of the sealers caused bacterial growth inhibition. Their
      effectiveness, in descending order of antimicrobial activity, was as follows:
      Endomethasone, Sultan, Sealapex, Diaket, Epiphany and AH 26. Epiphany sealer had
      little effect on the tested microorganism. The effectiveness of the root canal
      sealers decreased marginally with greater duration of incubation. CONCLUSIONS:
      The Epiphany root canal sealer offered no antibacterial advantage over the other
      sealers tested.

PMID- 16978483
TI  - Twenty-year follow-up of an unconventional intentional replantation.
AB  - For many years, intentional replantation has been a treatment option for pulpless
      teeth and an effective strategy for teeth that would be difficult, if not
      impossible, to treat using traditional root canal therapy. The preservation of
      cell vitality in the periodontal ligament, the removal of all tissue debris and
      irritating substances from the root surface, achievement of a good apical seal
      and reinforcement of the crown structure are critical in ensuring normal function
      of the reimplanted tooth. In this article, we report on an unconventional
      intentional replantation of a mandibular second molar to relieve continuing
      symptoms. Retrograde fillings were placed in the second molar and the coronal
      pulp chamber was sealed with amalgam. No endodontic therapy was carried out
      either during or after the procedure. After 20 years, the patient was
      asymptomatic, the tooth was still functional and a recall intraoral periapical
      radiograph showed an intact periodontal ligament space and lamina dura with no
      evidence of gross root resorption or ankylosis.

PMID- 16978484
TI  - Primary tuberculous gingival enlargement: a rare entity.
AB  - With the advent of effective drug therapy, tuberculous lesions of the oral cavity
      have become so rare that they are frequently forgotten. Primary gingival
      tuberculosis is extremely rare and usually manifests as ulcer. We report the
      first case of primary tuberculosis manifesting as gingival enlargement, which was
      the only presenting sign of tuberculosis. Diagnosis was based on histopathology
      (hematoxin and eosin staining), complete blood count, polymerase chain reaction
      assay and immunologic investigation with the detection of antibodies against
      Mycobacterium tuberculosis. The possibility of gingival enlargement due to drugs,
      leukemia, fungus and sarcoidosis was ruled out. Antituberculous therapy over 6
      months was followed by surgical excision of the residual enlargement under local
      anesthesia. After 1-year follow-up there was no recurrence of the disease. This
      case emphasizes the need for dentists to include tuberculosis in the differential
      diagnosis of gingival enlargement so that they may play a role in its early
      detection.

PMID- 16978485
TI  - Multiple odontogenic keratocysts: report of a case.
AB  - Although odontogenic keratocysts are common in clinical practice, the
      simultaneous occurrence of multiple cysts in both the maxilla and mandible of a
      patient is rare. We report a case of an otherwise healthy individual who
      developed 17 cysts over 15 years.

PMID- 16978487
TI  - Images of Appalachia.

PMID- 16978488
TI  - Appalachia: where place matters in health.

PMID- 16978489
TI  - Body mass index and blood pressure screening in a rural public school system: the
      Healthy Kids Project.
AB  - INTRODUCTION: All students (N = 2053) in Anadarko public schools, grades
      kindergarten through 12, were invited to be screened for height, weight, and
      blood pressure to assess the health status of this multiracial, multiethnic
      (American Indian, white, African American, and Hispanic) population in
      southwestern Oklahoma. METHODS: The Centers for Disease Control and Prevention's
      2000 growth charts were used to determine body mass index (BMI) percentiles, and
      standards from the National High Blood Pressure Education Program Working Group
      on Hypertension Control in Children and Adolescents were used to assess blood
      pressure. RESULTS: Seven hundred sixty-nine students with active consent
      participated in the screening. Of these, approximately 28% were overweight.
      American Indians were at significantly greater risk of being overweight or at
      risk for overweight than whites (relative risk [RR], 1.4; 95% confidence interval
      [CI], 1.1-1.7) as were African Americans (RR, 1.5; 95% CI, 1.1-2.0), whereas
      Hispanics (RR, 1.3; 95% CI, 0.9-2.0) did not have a statistically significant
      increased risk compared with whites. BMI at or above the 95th percentile was
      strongly associated with elevated blood pressure (> or =90th percentile) (RR,
      3.8; 95% CI, 2.6-5.4). CONCLUSION: Students who participated in this BMI
      screening in the Anadarko public school system evidenced high rates of excess
      weight, with American Indians and African Americans at greatest risk. Elevated
      BMI was strongly associated with elevated blood pressure.

PMID- 16978490
TI  - Risk of tooth loss after cigarette smoking cessation.
AB  - INTRODUCTION: Little is known about the effect of cigarette smoking cessation on
      risk of tooth loss. We examined how risk of tooth loss changed with longer
      periods of smoking abstinence in a prospective study of oral health in men.
      METHODS: Research subjects were 789 men who participated in the Veterans
      Administration Dental Longitudinal Study from 1968 to 2004. Tooth status and
      smoking status were determined at examinations performed every 3 years, for a
      maximum follow-up time of 35 years. Risk of tooth loss subsequent to smoking
      cessation was assessed sequentially at 1-year intervals with multivariate
      proportional hazards regression models. Men who never smoked cigarettes, cigars,
      or pipes formed the reference group. Hazard ratios were adjusted for age,
      education, total pack-years of cigarette exposure, frequency of brushing, and use
      of floss. RESULTS: The hazard ratio for tooth loss was 2.1 (95% confidence
      interval [CI], 1.5-3.1) among men who smoked cigarettes during all or part of
      follow-up. Risk of tooth loss among men who quit smoking declined as time after
      smoking cessation increased, from 2.0 (95% CI, 1.4-2.9) after 1 year of
      abstinence to 1.0 (95% CI, 0.5-2.2) after 15 years of abstinence. The risk
      remained significantly elevated for the first 9 years of abstinence but
      eventually dropped to the level of men who never smoked after 13 or more years.
      CONCLUSION: These results indicate that smoking cessation is beneficial for tooth
      retention, but long-term abstinence is required to reduce the risk to the level
      of people who have never smoked.

PMID- 16978491
TI  - Perceived barriers to walking for physical activity.
AB  - INTRODUCTION: Although the health benefits of walking for physical activity have
      received increasing research attention, barriers specific to walking are not well
      understood. In this study, questions to measure barriers to walking for physical
      activity were developed and tested among college students. The factor structure,
      test-retest and internal consistency reliability, and discriminant and criterion
      validity of the perceived barriers were evaluated. METHODS: A total of 305
      undergraduate students participated. Participants had a mean age (+/- SD) of 20.6
      (+/- 3.02) years, and 70.3% were female. Participants responded to a
      questionnaire assessing barriers specific to walking for physical activity.
      Perceived barriers to vigorous exercise, walking for transportation and
      recreation, and participation in lifestyle activities (such as taking the stairs
      instead of the elevator) were also assessed. Subsamples completed the walking
      barriers instrument a second time after 5 days in order to determine test-retest
      reliability (n = 104) and wore an accelerometer to measure moderate-intensity
      physical activity (n = 85). RESULTS: Factor analyses confirmed the existence of
      three factors underlying the perceived barriers to walking questions: appearance
      (four items), footwear (three items), and situation (three items). Appearance and
      situational barriers demonstrated acceptable reliability, discriminant validity,
      and relations with physical activity criteria. After we controlled for barriers
      to vigorous exercise, appearance and situational barriers to walking explained
      additional variation in objectively-measured moderate physical activity.
      CONCLUSION: The prediction of walking for physical activity, especially walking
      that is unstructured and spontaneous, may be improved by considering appearance
      and situational barriers. Assessing barriers specific to walking may have
      important implications for interventions targeting walking as means for engaging
      in physical activity.

PMID- 16978492
TI  - Rates and predictors of colorectal cancer screening.
AB  - INTRODUCTION: Despite widespread recommendations for colorectal cancer screening,
      the U.S. screening rate is low. The objectives of this study were to describe the
      rates and predictors of colorectal cancer screening use by examining groups in
      two categories--1) those who have ever been screened and 2) those with up-to-date
      screening--and to assess whether trends and predictors change over time. METHODS:
      We analyzed data from the 2000 and 2003 National Health Interview Surveys about
      the use of fecal occult blood tests, sigmoidoscopies, and colonoscopies for
      adults aged 50 years and older and without a history of colorectal cancer (N =
      11,574 in 2000 and N = 11,779 in 2003). RESULTS: Rates in the 2000 study
      population of those who have ever been screened for colorectal cancer (53%) had
      increased in the 2003 study population (55%) as had the rates in the 2003 study
      population of those with up-to-date colorectal screening (53%) compared with the
      rates in the 2000 study population (38%). Among those who were ever screened, 76%
      were up-to-date with screening in 2003, compared with 68% in 2000. There was
      increased use of colonoscopies but decreased use of fecal occult blood tests and
      sigmoidoscopies. Individuals were more likely to be up-to-date with screening if
      they had higher income, higher education, insurance coverage, a usual source of
      care, and a dental visit in the last year than if these predictors were not
      evident. Since 2000, these predictors of colorectal cancer screening use have
      remained stable. CONCLUSION: Although there has been relatively limited success
      in increasing overall screening, it is encouraging that most people in the group
      of those who have ever been screened are up-to-date with colorectal cancer
      screening. Predictors for colorectal screening were stable over time despite
      changes in screening policies and rates. Further research is needed to uncover
      barriers to colorectal cancer screening.

PMID- 16978493
TI  - The Rapid Assessment of Physical Activity (RAPA) among older adults.
AB  - INTRODUCTION: The Rapid Assessment of Physical Activity (RAPA) was developed to
      provide an easily administered and interpreted means of assessing levels of
      physical activity among adults older than 50 years. METHODS: A systematic review
      of the literature, a survey of geriatricians, focus groups, and cognitive
      debriefings with older adults were conducted, and an expert panel was convened.
      From these procedures, a nine-item questionnaire assessing strength, flexibility,
      and level and intensity of physical activity was developed. Among a cohort of 115
      older adults (mean age, 73.3 years; age range, 51-92 years), half of whom were
      regular exercisers (55%), the screening performance of three short self-report
      physical activity questionnaires--the RAPA, the Behavioral Risk Factor
      Surveillance System (BRFSS) physical activity questions, and the Patient-centered
      Assessment and Counseling for Exercise (PACE)--was compared with the Community
      Healthy Activities Model Program for Seniors (CHAMPS) as the criterion. RESULTS:
      Compared with the BRFSS and the PACE, the RAPA was more positively correlated
      with the CHAMPS moderate caloric expenditure (r = 0.54 for RAPA, r = 0.40 for
      BRFSS, and r = 0.44 for PACE) and showed as good or better sensitivity (81%),
      positive predictive value (77%), and negative predictive value (75%) as the other
      tools. Specificity, sensitivity, and positive predictive value of the questions
      on flexibility and strength training were in the 80% range, except for
      specificity of flexibility questions (62%). Mean caloric expenditure per week
      calculated from the CHAMPS was compared between those who did and those who did
      not meet minimum recommendations for moderate or vigorous physical activity based
      on these self-report questionnaires. The RAPA outperformed the PACE and the
      BRFSS. CONCLUSION: The RAPA is an easy-to-use, valid measure of physical activity
      for use in clinical practice with older adults.

PMID- 16978495
TI  - Community intervention to promote consumption of fruits and vegetables, smoke
      free homes, and physical activity among home caregivers in Bogota, Colombia.
AB  - INTRODUCTION: We conducted a pilot study to develop and assess the effectiveness
      of three interventions to promote consumption of fruits and vegetables, promote
      physical activity, and negotiate smoke-free homes among home caregivers in
      Bogota, Colombia. Colombian home caregivers were defined as women who take care
      of minors in their local communities regardless of kinship or family ties.
      METHODS: A nonrandomized community intervention was conducted in low
      socioeconomic status neighborhoods in Bogota. Ninety-seven women aged 18 to 60
      years participated in one of three groups. In groups A and B, women received the
      following components: information and communication about healthy behaviors (with
      group A receiving additional activities); education about developing decision
      making skills; and social support from family members and others. In group C,
      women received only the information and communication component received by group
      B. The main outcomes (measured at baseline, immediately after the intervention at
      5 months, and at 7 months) included self-reported consumption of fruits and
      vegetables, whether there was an agreement form signed by family members to
      refrain from smoking inside the home, and self-reported level of physical
      activity. RESULTS: No differences were found between intervention groups.
      Regardless of the intervention, there was an increase in the proportion of women
      who reported consuming juices made from fruit (from 51.5% at baseline to 80.9% at
      7 months, P <.001), an increase in the proportion of women who reported daily
      consumption of vegetables or salad (from 44.1% at baseline to 64.7% at 7 months,
      P < .001), and an increase in the proportion of homes with an agreement that
      forbids in-home smoking (from 27.9% at baseline to 44.1% at 7 months, P = .04).
      There was no significant difference in levels of physical activity from baseline
      to postintervention. CONCLUSION: Home caregivers may be responsive to community
      interventions associated with the promotion of healthy diet and agreements with
      family members who smoke to refrain from smoking in the home.

PMID- 16978494
TI  - Identifying supports and barriers to physical activity in patients at risk for
      diabetes.
AB  - INTRODUCTION: Recent clinical trials have demonstrated that increasing physical
      activity among patients at risk for diabetes can prevent or delay the onset of
      type 2 diabetes. In this study, we surveyed primary care patients at risk for
      diabetes to 1) describe physical activity habits, supports, and barriers; 2)
      identify characteristics associated with increased physical activity; and 3)
      develop and assess the psychometric properties of an instrument that measures
      influences on physical activity. METHODS: A cross-sectional sample of 522 high
      risk adults who attended 14 North Carolina primary care family practices were
      mailed a survey about physical activity and supports of and barriers to physical
      activity. Risk status was determined by the American Diabetes Association's
      diabetes risk test. Exploratory principal components factor analyses were
      conducted on the influences on physical activity instrument. Predictive logistic
      regression models were used for the dichotomous outcome, meeting recommended
      Healthy People 2010 activity levels. RESULTS: Of the 258 respondents (56%
      response rate), 56% reported at least 150 minutes of moderate or vigorous
      activity per week. Higher education remained a significant demographic predictor
      of activity (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.08-2.75).
      Participants were less likely to be physically active if they reported that
      activity is a low priority (OR, 0.45; 95% CI, 0.23-0.89), were worried about
      injury (OR, 0.42; 95% CI, 0.25-0.69), or had difficulty finding time for activity
      (OR, 0.38; 95% CI, 0.17-0.87). CONCLUSION: Participants at risk for diabetes who
      prioritize physical activity, make time for activity, and are less worried about
      injury have higher odds of being physically active. Primary care practice and
      community interventions should consider targeting these areas of success to
      increase physical activity in sedentary individuals at risk for diabetes.

PMID- 16978496
TI  - Estimating chronic disease deaths and hospitalizations due to alcohol use in
      Canada in 2002: implications for policy and prevention strategies.
AB  - INTRODUCTION: Alcohol consumption is a factor that increases risk of chronic
      disease. This study estimates various indicators of alcohol-attributable
      premature chronic-disease morbidity and mortality for Canada in 2002. METHODS:
      Information on mortality and morbidity was obtained from Statistics Canada and
      from the Canadian Institute for Health Information database. Data on alcohol use
      were obtained from the Canadian Addiction Survey and weighted for per capita
      consumption. Risk information was taken from published literature and combined
      with alcohol consumption information to calculate age- and sex-specific alcohol
      attributable chronic disease morbidity and mortality. RESULTS: In Canada in 2002,
      there were 1631 chronic disease deaths among adults aged 69 years and younger
      attributed to alcohol consumption, and these deaths were 2.4% of the deaths in
      Canada for this age group. The net number of deaths comprised 2577 deaths caused
      and 947 deaths prevented by alcohol consumption. Moderate drinking was involved
      in 25% of deaths caused and 85% of deaths prevented by alcohol. There were 42,996
      years of life lost prematurely in Canada due to alcohol consumption in 2002,
      28,890 for men and 14,106 for women. In Canada in 2002, there were 91,970 net
      chronic disease hospitalizations attributed to alcohol consumption among
      individuals aged 69 years and younger. The net numbers were 124,621
      hospitalizations caused and 32,651 hospitalizations prevented by alcohol
      consumption. CONCLUSION: With rising rates of alcohol consumption and extensive
      high-risk drinking, both chronic and acute damage from alcohol are expected to
      increase. Attention is needed to 1) create effective policies and interventions;
      2) control access to alcohol; 3) reduce high-risk drinking; and 4) provide brief
      interventions for high-risk drinkers.

PMID- 16978497
TI  - Initiatives of 11 rural Appalachian cancer coalitions in Pennsylvania and New
      York.
AB  - INTRODUCTION: Local coalitions combine the knowledge, expertise, and resources of
      many individuals and organizations to improve community health. This article
      describes data from 11 rural cancer coalitions in Pennsylvania and New York
      collected through a model-based data system. METHODS: The coalition data
      collection system was adapted from a conceptual model designed to monitor the
      activities and impact of cardiovascular disease coalitions. Community Coalition
      Action Theory was used during implementation and validation of the data system.
      Primary components of the data system were organizational capacity, process, and
      outcome/impact. RESULTS: From 2002 to 2004, the 11 coalitions conducted 1369
      initiatives, including 1147 (83.8%) interventions and 222 (16.2%) development
      activities. Among interventions, 776 (56.7%) were outreach only, 158 (11.5%)
      education only, 117 (8.5%) outreach and education, and 96 (7.0%) screening.
      Differences in the distribution of initiatives by coalition, cancer site, and
      target audience were statistically significant (P < .05). The majority of
      interventions focused on colorectal (37.0%) and breast (32.9%) cancer. Target
      groups included women (71.3%), rural residents (32.6%), survivors (21.8%), and
      low-income (21.8%) individuals. Although not statistically significant, an
      observed 3-year trend was shown for decreased outreach interventions and
      increased education and screening interventions. In total, 1951 of 3981
      individuals who were offered a cancer screening (49%) completed screening, and 15
      sustainable community changes were documented. CONCLUSION: This study reports the
      initiatives and impact of 11 rural community cancer coalitions over a 3-year
      period. This study estimates the mix of development activities and community
      interventions, against which this coalition network and others may be compared.

PMID- 16978498
TI  - Knowledge, barriers, and predictors of colorectal cancer screening in an
      Appalachian church population.
AB  - INTRODUCTION: This study examined knowledge about and barriers to colorectal
      cancer screening and predictors of screening adherence among members from 16
      Appalachian churches as part of a larger study on the prevention and early
      detection of colorectal cancer. METHODS: Baseline data were collected on 839
      respondents aged 50 years and older through a self-administered survey, and 23
      focus groups were conducted with 205 church members RESULTS: Survey results
      showed that older age, male sex, being current for other cancer screening, being
      physically active, having perceived support from others for screening, better
      provider communication, knowledge about screening guidelines, greater perceived
      susceptibility to colorectal cancer, and a family history of the disease were
      predictors of screening adherence. Major barriers to screening in both surveys
      and focus groups were failure of providers to recommend screening, lack of
      knowledge about the need for screening, and the belief that screening was not
      necessary without symptoms. Fear of cancer, lack of knowledge about screening
      methods other than colonoscopy, reliance on physicians for screening information,
      and the need for people to feel at risk for screening to occur were other
      findings from the focus groups. Focus groups supported survey findings and
      provided further insights. CONCLUSION: Several factors predictive of colorectal
      cancer screening in this study can be modified through educational interventions.
      Recognizing and changing risk factors for colorectal cancer, raising awareness of
      screening guidelines, and encouraging adults aged 50 years and older to discuss
      screening with their health care provider could increase colorectal cancer
      screening.

PMID- 16978499
TI  - Social and cultural factors influencing health in southern West Virginia: a
      qualitative study.
AB  - INTRODUCTION: Social, cultural, and economic environments are associated with
      high rates of disease incidence and mortality in poor Appalachian regions of the
      United States. Although many historical studies suggest that aspects of
      Appalachian culture (e.g., fatalism, patriarchy) include values and beliefs that
      may put Appalachians at risk for poor health, other cultural aspects may be
      protective (e.g., strong social ties). Few recent studies have explored regional
      cultural issues qualitatively. The purpose of this study was to examine social
      and cultural factors that may be associated with health and illness in an
      Appalachian region. METHODS: Ten focus groups were conducted in southern West
      Virginia and included five groups of men and five groups of women. Cultural norms
      associated with residents of rural Appalachia, such as faith, family values, and
      patriarchy, were examined. RESULTS: Both men and women in the focus groups have a
      sense of place, strong family ties, and a strong spiritual belief or faith in
      God. Patriarchy as a cultural value was not a strong factor. CONCLUSION: There
      are limits to how qualitative data may be used, but findings from this study help
      increase understanding of the social and cultural environments of people living
      in rural Appalachia and how these environments may affect health.

PMID- 16978500
TI  - Assessing awareness and knowledge of breast and cervical cancer among Appalachian
      women.
AB  - INTRODUCTION: West Virginia is the only state that lies entirely within
      Appalachia. West Virginians tend to be poorer and more likely to lack health
      insurance than the general U.S. population. The purpose of this qualitative study
      was to 1) obtain an understanding of attitudes about breast and cervical cancer
      screening among women aged 25 to 64 years; 2) determine factors that motivate
      women to be screened for breast and cervical cancer; and 3) evaluate educational
      materials about breast and cervical cancer screening for use in this population.
      METHODS: The West Virginia Breast and Cervical Cancer Screening Program (WVBCCSP)
      is a comprehensive public health program, funded by the Centers for Disease
      Control and Prevention, dedicated to removing barriers to breast and cervical
      cancer screening and providing screenings to underserved women aged 25 to 64
      years. The program partnered with RMS Strategies, Inc, to conduct six focus
      groups in three communities in West Virginia. Women were recruited by telephone
      based on program eligibility guidelines. RESULTS: Results indicated that women
      were concerned about health care costs and lack of health insurance. Cost, fear,
      and embarrassment were identified as the top barriers to breast and cervical
      cancer screening. Participants believed that community-based educational
      campaigns would increase screening and promote use of the WVBCCSP. CONCLUSION:
      Understanding why low-income Appalachian women do not get screened for breast and
      cervical cancer and determining motivational factors that encourage screening are
      important to increase screening rates among this population. Breast and cervical
      cancer efforts that use the words, knowledge, and suggestions of the women they
      serve are more likely to be effective and have a larger impact.

PMID- 16978501
TI  - Talking parents, healthy teens: a worksite-based program for parents to promote
      adolescent sexual health.
AB  - Parents play an important role in the sexual health of their adolescent children.
      Based on previous research, formative research, and theories of behavioral
      change, we developed Talking Parents, Healthy Teens, an intervention designed to
      help parents improve communication with their adolescent children, promote
      healthy adolescent sexual development, and reduce adolescent sexual risk
      behaviors. We conduct the parenting program at worksites to facilitate
      recruitment and retention of participants. The program consists of 8 weekly 1
      hour sessions during the lunch hour. In this article, we review the literature
      that identifies parental influences on adolescent sexual behavior, summarize our
      formative research, present the theoretical framework we used to develop Talking
      Parents, Healthy Teens, describe the program's components and intervention
      strategies, and offer recommendations based on our experiences developing the
      program. By targeting parents at their worksites, this program represents an
      innovative approach to promoting adolescent sexual health. This article is
      intended to be helpful to health educators and clinicians designing programs for
      parents, employers implementing health-related programs, and researchers who may
      consider designing and evaluating such worksite-based programs.

PMID- 16978502
TI  - Risky behaviors among Ohio Appalachian adults.
AB  - This article describes the prevalence of risky behaviors known to be associated
      with increased cancer morbidity and mortality among Ohio Appalachian adults.
      These behaviors, or risk factors, include: 1) tobacco use; 2) energy imbalance
      (involving poor diet, obesity, and physical inactivity); and 3) sexual behaviors.
      We report current estimates of the prevalence of these behaviors among Ohio
      Appalachian adult residents and review social, psychological, and biological
      variables associated with these risky behaviors. We also present recent empirical
      studies that have been completed or are in progress in Ohio Appalachia. Finally,
      we discuss how these studies help bridge well-documented gaps in the literature.

PMID- 16978503
TI  - The Great Lakes Regional Stroke Network experience.
AB  - Stroke is a leading cause of disability and the third leading cause of death
      among adults in the United States and in the Great Lakes states of Illinois,
      Indiana, Michigan, Minnesota, Ohio, and Wisconsin. The Great Lakes Regional
      Stroke Network was created to enhance collaboration and coordination among the
      Great Lakes states to reduce the burden of stroke and stroke-related disparities
      associated with race, sex, and geography. Three priorities were identified for
      reducing the effects of stroke in the Great Lakes region: 1) build epidemiologic
      capacity to improve stroke prevention and control efforts, 2) facilitate systems
      level changes and collaborative efforts to improve acute stroke care and
      rehabilitation, and 3) promote awareness of the warning signs of stroke and the
      need to call 911. The Great Lakes Regional Stroke Network has work groups in the
      areas of epidemiology and surveillance, health care quality improvement, and
      public education. These groups recommend initiatives to states for their efforts
      to reduce the effects of stroke within the Great Lakes region. Examples of
      recommended initiatives include identifying and prioritizing state research
      evaluation needs for stroke, conducting a stroke education media campaign, and
      developing a statewide emergency medical services protocol for stroke.

PMID- 16978506
TI  - [To develop further study on occupational stress].

PMID- 16978504
TI  - An easy approach to calculating estimated energy requirements.
AB  - The Dietary Reference Intakes (DRIs) define the daily requirement for energy as
      the Estimated Energy Requirement (EER). The EER is based on calculations that
      account for an individual's energy intake, energy expenditure, age, sex, weight,
      height, and physical activity level. Including physical activity level in the
      calculations makes determining energy expenditure possible and achieving energy
      balance a more realistic goal. However, physical activity level is often
      difficult to measure and accurate assessment of energy expenditure not always
      possible. We provide an easy way to calculate daily EERs for adults based on
      physical activity level. We use the EER equations of the DRI Committee and
      provide a spreadsheet template for the calculation of physical activity level.
      This technique accounts for all factors and measurements to determine physical
      activity level and energy expended from daily physical activity. It should prove
      a useful approach in research, clinical, and public health settings.

PMID- 16978507
TI  - [Hierarchical regression analysis for relationship between job stress and job
      burnout in Shanghai employees].
AB  - OBJECTIVE: To identify related factors of job burnout in Shanghai employees.
      METHODS: Four hundred fifty-six employees in Shanghai were investigated in this
      study. Self-administered questionnaires were used to assess job burnout and job
      stress, based on Maslach Burnout Inventory and the Job Demand-Control model as
      well as Effort-Reward Imbalance Model. Hierarchical linear regression was
      employed to analyze the relationship of job burnout to personal characteristics
      and job stress. RESULTS: The indexes of three dimensions of job burnout were
      emotional exhaustion 19.70 +/- 8.92, depersonalization 11.95 +/- 4.45 and reduced
      personal accomplishment 28.10 +/- 10.08. Job stress was found to be affected
      differently in three dimensions of job burnout. Job demand, effort and over
      commitment had positive impact on emotional exhaustion. Job control had a
      negative association with emotional exhaustion. There were significant
      relationship between depersonalization and age, sex and education of employees.
      Job control, reward and over-commitment affected the index of depersonalization.
      Education level and social support increased personal accomplishment index.
      CONCLUSION: It is necessary to reduce job stress and care about personal
      characteristics in preventing job burnout.

PMID- 16978509
TI  - [Risk factors of nurses' occupational adaptability].
AB  - OBJECTIVE: To explore factors affecting occupational adaptability in nurses for
      offering basis to increase their occupational adaptability. METHODS: Five hundred
      and forty-five nurses were investigated with work ability index questionnaire and
      occupational stress instruments. RESULTS: There were many risk factors affecting
      occupational adaptability in nurses. The main variables that influenced
      occupational adaptability included work-overtime, mental load, social support,
      physical environment, and job hazards. The social support was the factor
      increasing the occupational adaptability of the nurses (P < 0.01, OR = 0.912).
      Five factors including work overtime, mental load, social support, physical
      environment and job hazards were introduced in the Logistic equation. The
      established functions were: Logit (P) = -11.357 + 1.011x(1) + 0.335x(2) -
      0.076x(3) + 0.260x(4) + 0.129x(5). CONCLUSION: There are many risk factors
      affecting occupational adaptability in nurses. Relevant measures should be taken
      to promote the occupational adaptability in nurses to reduce the risk factors.

PMID- 16978508
TI  - [Association between social psychological factors and depressive symptoms among
      healthcare workers].
AB  - OBJECTIVE: To explore the association between the effort-reward imbalance at work
      and depressive symptoms among healthcare workers. METHODS: The effort-reward
      imbalance at work was conceptualized in terms of the Chinese version of the
      effort-reward imbalance (ERI) model. Depressive symptoms were assessed by the
      Chinese version of the Center of Epidemiology Survey Depression (CES-D) scale.
      The data came from the cross-sectional survey of 1 179 healthcare workers aged
      between 18 and 73 employed in 6 affiliated hospitals of Zhejiang University. The
      questionnaire comprised questions on the effort-reward at work, over-commitment,
      the full CES-D scale of depression and a range of other characteristics.
      Univariate analyses were used with Spearman's correlation, Mann-Whitney test,
      Pearson chi(2) test and likelihood chi(2) test. Multivariate logistic regression
      analyses was used to discover factors associated with depressive symptoms.
      RESULTS: The prevalence of depressive symptoms among healthcare workers was
      48.12% (95% CI: 45.08% to 51.16%). The prevalence of depressive symptoms among
      nurses was 52.40% (95% CI: 47.87% to 56.93%) higher than doctors' 44.70% (95% CI:
      10.64% to 48.77%) with the significant difference (chi(2) = 6.077, P = 0.014).
      Positive associations were found between the high effort-low reward, level of
      work-related over commitment and depressive symptoms (OR = 1.859, 95% CI: 1.337
      to 2.585; OR = 2.207, 95% CI: 1.656 to 2.942) among healthcare workers,
      respectively. CONCLUSION: The high effort-low reward and the work-related over
      commitment have a negative impact on healthcare workers' health.

PMID- 16978510
TI  - [An accident of acute hydrogen sulfide poisoning].

PMID- 16978511
TI  - [GSM 1,800 MHz radiofrequency electromagnetic fields induced clustering of
      membrane surface receptors and interference by noise magnetic fields].
AB  - OBJECTIVE: To investigate the possible effect of exposure to GSM 1,800 MHz
      radiofrequency electromagnetic fields (RF EMF) on epidermal growth factor (EGF)
      receptor and its possible interference by noise magnetic fields (MF). METHODS:
      Chinese hamster lung fibroblasts (CHL) were exposed to 1,800 MHz RF EMF
      (modulated by 217 Hz or 50 Hz, or unmodulated), 2 microT noise MF, and RF EMF
      combined with 2 microT noise MF for 15 min, respectively. The specific absorption
      rates (SARs) of RF EMF were 0.1, 0.5, 1.0, 2.0 and 4.0 W/kg. Commercial EGF (1
      ng/ml) treatment was used as positive control. EGF receptors on the cell membrane
      were observed under a laser scanning confocal microscope after indirect
      immunofluorescence staining. RESULTS: EGF receptor clustering was induced after
      exposure to GSM 1,800 MHz RF EMF modulated by 217 Hz or 50 Hz MF at SARs of 0.5,
      1.0, 2.0, 4.0 W/kg for 15 min as induced by 1 ng/ml EGF, but not at SAR of 0.1
      W/kg. And no EGF receptor clustering was found in cells after exposure to
      unmodulated RF EMF or 2 microT noise MF. In addition, superposition of 2 microT
      noise MF could inhibit the EGF receptor clustering induced by GSM 1,800 MHz RF
      EMF. CONCLUSION: EGF receptor clustering in CHL cells can be induced by GSM 1,800
      MHz RF EMF at the lowest SAR of 0.5 W/kg and inhibited by noise MF. The
      modulation of wave may play an important role in the inducement of receptor
      clustering after RF exposure.

PMID- 16978512
TI  - [Effect of acute exposure to microwave from mobile phone on DNA damage and repair
      of cultured human lens epithelial cells in vitro].
AB  - OBJECTIVE: To investigate the DNA damage of human lens epithelial cells (LECs)
      caused by acute exposure to low-power 217 Hz modulated 1.8 GHz microwave
      radiation and DNA repair. METHODS: Cultured LECs were exposed to 217 Hz modulated
      1.8 GHz microwave radiation at SAR (specific absorption rate) of 0, 1, 2, 3 and 4
      W/kg for 2 hours in an sXc-1800 incubator and irradiate system. The DNA single
      strand breaks were detected with comet assay in sham-irradiated cells and
      irradiated cells incubated for varying periods: 0, 30, 60, 120 and 240 min after
      irradiation. Images of comets were digitized and analyzed using an Imagine-pro
      plus software, and the indexes used in this study were tail length (TL) and tail
      moment (TM). RESULTS: The difference in DNA-breaks between the exposure and sham
      exposure groups induced by 1 and 2 W/kg irradiation was not significant at every
      detect time (P > 0.05). As for the dosage of 3 and 4 W/kg there was difference in
      both group immediately after irradiation (P < 0.01). At the time of 30 min after
      irradiation the difference went on at both group (P < 0.01). However, the
      difference disappeared after one hour's incubation in 3 W/kg group (P > 0.05),
      and existed in 4 W/kg group. CONCLUSION: No or repairable DNA damage was observed
      after 2 hour irradiation of 1.8 GHz microwave on LECs when SAR < or = 3 W/kg. The
      DNA damages caused by 4 W/kg irradiation were irreversible.

PMID- 16978513
TI  - [Effects of exposure to extremely low frequency electromagnetic fields on
      reproduction of female mice and development of offsprings].
AB  - OBJECTIVE: To observe the effects of exposure to extremely low frequency
      electromagnetic fields (ELF EMFs) on pregnant mice and development of offsprings.
      METHODS: Female mice were exposed to 50 Hz, 1.2 mT electromagnetic fields during
      the whole pregnant period (8 h/d). The body weight of dams, delivery and
      development of offsprings were observed and measured. RESULTS: The increase of
      body weight of exposed dams (29.0%) was significantly slower than that of the
      control group (47.8%) during late pregnancy period (P < 0.05). The producing rate
      of exposed group was 60% of that of control group. Miscarriage, fetal loss and
      externally malformed fetus appeared in exposed group. The average number of
      offsprings of each exposed mouse was significantly decreased (11 +/- 1.6 vs 7 +/-
      2.0, P < 0.05) and 11 for control group. Regarding the development of offspring,
      the body weight of prenatally exposed offsprings was increased more slowly than
      that of the control in the first two weeks after birth (P < 0.05). Developmental
      manifestations including eye opening [(252 +/- 24) h] and tooth eruption [(336 +/
      19) h] presented later in exposed offspring [(226 +/- 12), (319 +/- 15) h,
      respectively] (P < 0.05). CONCLUSION: Exposure to ELF EMFs during pregnancy
      period can cause adverse effects on pregnancy of female mice and development of
      offsprings.

PMID- 16978514
TI  - [Polymorphisms of hsp 60 gene in Chinese Han people].
AB  - OBJECTIVE: To identify the single nucleotide polymorphisms (SNPs) in the
      regulatory and coding regions of heat shock protein 60 gene and search for its
      genetic makers in Chinese Han people. METHODS: The 5' flank region, parts of the
      exons and introns of hsp60 gene were resequenced to identify the SNPs in Chinese
      Han people, and then the sequenced results to the Japanese, European and
      African's data in National Center for Biotechnology Information (NCBI) and HapMap
      databases were compared. RESULTS: One novel SNP was identified in exon 2
      resulting in synonymous variant and the G allele frequency was 0.025. There were
      11 reported SNPs in the sequenced region. The minor allele frequencies of
      rs1116734, rs3749095, rs1050347, rs8539 were 0.51, 0.30, 0.29, 0.49. The
      heterozygosity of the other 7 SNPs was 0. The distributions of rs1116734,
      rs1050347, rs8539, rs3749095 in Chinese Han people were similar to the
      Japanese's. The hsp60 rs3749095 which was not found in Japanese people was a high
      frequency SNP in Chinese Han people; the distribution of rs8539 in Chinese Han
      people was quite different from European and African's (P < 0.01). CONCLUSION:
      The SNPs of hsp60 in Chinese Han people are different from the other peoples. The
      SNPs of hsp60 gene rs1116734, rs3749095, rs1050347, rs8539 are very common in
      Chinese Han people and might be used for candidate genetic markers of hsp60 gene.

PMID- 16978516
TI  - [Relationship between polymorphisms of DNA repair gene XRCC1 and susceptibility
      to radiation injury].
AB  - OBJECTIVE: To explore the relationship between polymorphisms of DNA repair gene
      XRCC1 and susceptibility to radiation injury. METHODS: In 1:1 case-control study,
      113 abnormal chromosome workers exposed to ionizing radiation were selected as
      cases and 113 normal chromosome as controls who matched with case for sex, age
      (+/- 5 years), nation, type of work, the same or more but in 2 years work length
      and the same similar levels of the cumulative exposure radiation dose. Genotypes
      were analysed using PCR based restriction fragment length polymorphism
      techniques. RESULTS: The frequency of XRCC1 26304TT allele in case group (18.58%)
      was significantly higher than that in control group (7.08%), with OR for
      radiation damage being 3.47 (95% CI 1.43 - 8.44, P < 0.05). No association was
      observed between XRCC1 G27466A and G28152A and susceptibility to radiation
      injury. CONCLUSION: The mutation of XRCC1 C26304T is related with the
      susceptibility to radiation injury. The polymorphisms of XRCC1 G27466A and
      G28152A are not found to have association with abnormal chromosomes.

PMID- 16978515
TI  - [Effects of selective iNOS inhibitor aminoguanidine on waveform of blood pressure
      in rat heat stroke].
AB  - OBJECTIVE: To evaluate the change of blood pressure, ECG and nitric oxide (NO) in
      rat heat stroke and effects of aminoguanidine (AG) against heatstroke. METHODS:
      The male SD rats were randomly assigned into 1 of the following 2 groups: control
      group or AG group. The rats of control group (n = 10) and AG group (n = 10) were
      exposed to high ambient temperature (41 degrees C, relative humidity 65%) to
      induce heatstroke, arterial blood pressures, colonic temperature (T(co)),
      electrocardiograph (ECG) were monitored. The other rats of both groups (both n =
      10) were exposed to high ambient temperature (41 degrees C, relative humidity
      65%), and the blood samples were taken at 0, 60 min after the start of heat
      exposure for determination of the plasma NO concentrations. RESULTS: (1) From 0
      min to 50 min after heat exposure, MAPs of two groups were not significantly
      different, but at about 55 approximately 60 min after the start of heat exposure,
      MAPs of control group were decreased significantly differently from that of AG
      group, K value and dicrotic pulse relative height (h(D)/H) were gradually
      decreased, especially at 40 min after the start of heat exposure, K value of
      control group decreased significantly comparison with that of AG group; (2) Heart
      rate (HR) and QT interval of both groups were increased, while PR interval were
      decreased after the start of heat exposure; (3) T(co) of both groups were
      increased after the start of heat exposure until T(co) increased to 42 degrees C
      (the onset of heatstroke), but there was not significantly difference between the
      two groups; (4) The time of the onset of heatstroke (TOHS) and survival time (ST)
      of AG group were significantly longer than those of control group; (5) The plasma
      NO concentrations of the two groups were significantly higher at 60 min than at 0
      min after the start of heat exposure, and the plasma NO concentrations of control
      group were significantly higher than that of AG group at 60 min after the start
      of heat exposure. CONCLUSION: iNOS may contribute to heatstroke, and
      aminoguanidine can provide protective effects on heatstroke as a selective iNOS
      inhibitor.

PMID- 16978517
TI  - [Effects of occupational stress on menstrual function of female knitting factory
      workers].

PMID- 16978518
TI  - [Risk factors of fatty liver disease among coke oven workers].

PMID- 16978519
TI  - [Investigation of relationship between occupational dermatoses in coal miners and
      their working environment].

PMID- 16978520
TI  - [Influence on physiological load of crewmen exposed to noise and noxious
      substances in compartments during tank gun shooting].

PMID- 16978521
TI  - [Experimental study on toxicity and changes of biochemical indicator in acute
      bromoxynil poisoning].

PMID- 16978522
TI  - [Influence on menstrual function of women exposed to occupational stress and its
      mechanism].

PMID- 16978523
TI  - [Research progress on biochemical mechanism of vibration-induced vascular
      impairment].

PMID- 16978524
TI  - [One case of acute hydrogen sulfide poisoning with pathological report].

PMID- 16978525
TI  - [Advance of nanotoxicology].

PMID- 16978526
TI  - [Therapy of encephalopathy induced by severe dichloroethane poisoning].

PMID- 16978527
TI  - [Three cases of severe occupational heat stroke].

PMID- 16978528
TI  - [Analysis of knowledge of occupational health care in forging and casting workers
      before and after health care education].

PMID- 16978529
TI  - [Disputes in assumption of organization liable for occupational diseases].

PMID- 16978530
TI  - [Analysis of occupational poisoning accidents].

PMID- 16978531
TI  - [Value of CR system in bedside X-ray for inhalation injury].

PMID- 16978532
TI  - The regulatory effect of natural killer cells: do "NK-reg cells" exist?
AB  - The most important progress in immunology in the last decade is the description
      of regulatory lymphocytes, among which Treg cells and regulatory NKT cells are
      much attractive to not only immunologists but also almost all biomedical
      researchers. Meanwhile, it is noted that NK cells are not only "Killers" but also
      regulate innate and adaptive immunity, especially in early stage, by secreting
      cytokines and cell-cell contact. In this review, we are going to briefly
      summarize the progresses in regulatory lymphocytes including T cells (Treg, Tr1,
      Th3), NKT cells and NK cells, and then extensively introduce the positive
      regulatory function of NK cells in both normal immune response and in disease
      condition (tumor, infection and autoimmunity), and finally, to focus on the most
      latest progression in the negative regulatory effects of NK cells on normal and
      pathogenic immune response. In conclusion, we speculate that a "regulatory NK (NK
      reg)" cell subset exist and need to explore.

PMID- 16978533
TI  - The ubiquitin-proteasome system and its role in inflammatory and autoimmune
      diseases.
AB  - Protein degradation through the ubiquitin-proteasome system is the major pathway
      of non-lysosomal proteolysis of intracellular proteins. It plays important roles
      in a variety of fundamental cellular processes such as regulation of cell cycle
      progression, division, development and differentiation, apoptosis, cell
      trafficking, and modulation of the immune and inflammatory responses. The central
      element of this system is the covalent linkage of ubiquitin to targeted proteins,
      which are then recognized by the 26S proteasome, an adenosine triphosphate
      dependent, multi-catalytic protease. Damaged, oxidized, or misfolded proteins as
      well as regulatory proteins that control many critical cellular functions are
      among the targets of this degradation process. Aberration of this system leads to
      the dysregulation of cellular homeostasis and the development of multiple
      diseases. In this review, we described the basic biochemistry and molecular
      biology of the ubiquitin-proteasome system, and its complex role in the
      development of inflammatory and autoimmune diseases. In addition, therapies and
      potential therapeutic targets related to the ubiquitin-proteasome system are
      discussed as well.

PMID- 16978534
TI  - Selective function of PKC-theta in T cells.
AB  - T cell activation is a critical process in initiating adaptive immune response
      since only through this process the naive antigen specific T cells differentiate
      into armed effector T cells that mediate the actual immune response. During T
      cell activation, naive T cells undergo clonal expansion and acquire the
      capability to kill target cells infected with pathogens or produce cytokines
      essential for regulating immune response. Inappropriate activation or
      inactivation of T cells leads to autoimmunity or severe immunodeficiencies. PKC
      theta is selectively expressed in T cells and required for mediating T cell
      activation process. Mice deficient in PKC-theta exhibit defects in T cell
      activation, survival and activation-induced cell death. PKC-theta selectively
      translocates to immunological synapse and mediates the signals required for
      activation of NF-kappaB, AP1 and NFAT that are essential for T cell activation.
      Furthermore, PKC-theta-/- mice displayed multiple defects in the development of T
      cell-mediated immune responses in vivo. PKC-theta is thus a critical molecule
      that regulates T cell function at multiple stages in T cell-mediated immune
      responses in vivo.

PMID- 16978535
TI  - Pivotal role of PGE2 and IL-10 in the cross-regulation of dendritic cell-derived
      inflammatory mediators.
AB  - Exposure to pathogens induces antigen-presenting cells (APC) such as macrophages
      and dendritic cells (DC) to produce various endogenous mediators, including
      arachidonic acid (AA)-derived eicosanoids, cytokines, and nitric oxide (NO). Many
      secreted products of activated APC can act by themselves in an autocrine manner
      and modulate their function. Moreover, the cross-interaction between endogenous
      bioactive molecules regulates the function of professional APC with important
      consequences for their ability to activate and sustain immune and inflammatory
      responses, and to regulate immune homeostasis. Although neglected for many years
      when compared to their role in cardiovascular homeostasis, cancer and
      inflammation, the importance of eicosanoids in immunology is becoming more
      defined. The role of prostaglandin (PG) E2 (PGE2), one of the best known and most
      well studied eicosanoids, is of particular interest. It modulates the activities
      of professional DC by acting on their differentiation, maturation and their
      ability to secrete cytokines. Uniquely among haematopoietic cytokines,
      interleukin-10 (IL-10) is a pleiotropic molecule that displays both
      immunostimulatory and immunoregulatory activities. IL-10 has attached much
      attention because of its anti-inflammatory properties. It modulates expression of
      cytokines, soluble mediators and cell surface molecules by cells of myeloid
      origin, particularly macrophages and DC. We previously reported that PGE2 is a
      potent inducer of IL-10 in bone marrow-derived DC (BM-DC), and PGE2-induced IL-10
      is a key regulator of the BM-DC pro-inflammatory phenotype. BM-DC may be
      considered as an important model to study complex interactions between endogenous
      mediators, and autocrine IL-10 plays a pivotal role in the crossregulation of AA
      derived lipid mediators, cytokines, and NO, with critical effects on immune and
      inflammatory responses.

PMID- 16978536
TI  - DC-SIGN and immunoregulation.
AB  - Dendritic cells (DCs) are known to be the most powerful professional antigen
      presenting cells so far. It could activate primary immune response, and also
      downregulate immune response. DCs have a unique character of immunoregulation. DC
      SIGN, a molecule designated as CD209, is one member of the C-type lectin
      superfamily. It is not only a pattern recognition receptor but implicated in
      immunoregulation of DCs. DC-SIGN has become hotspot of recent studies because of
      its important role in mediating DC adhesion, migration, inflammation, activating
      primary T cell, triggering immune response and participating in immune escape of
      pathogens and tumors. These studies on DC-SIGN involved in primary and secondary
      immune response and relevant mechanism will certainly provide us with a new
      method in treating and preventing certain diseases.

PMID- 16978537
TI  - The molecular mechanism of HDAC inhibitors in anticancer effects.
AB  - HDACs and HATs are two kinds of enzymes which catalyse deacetylation and
      acetylation of histone in eukaryotes, whose dynamic balance has accurate
      regulation for gene transcription and gene expression of eukaryotes at DNA level.
      Disbalance of them can bring the disorder of proliferation and differentiation in
      normal cells, and then lead to the initiation of tumor. Their aberrant functions
      were directly related to the initiation and progression of various tumors, such
      as promyelocytic leukemia, Hodgkin lymphoma, colonic cancer and gastral cancer.
      The inhibitors of HDACs are used for treatment of tumor. They can restrain the
      activity of HDACs and block the inhibition of gene expression caused by the
      disorder of deacetylation. Its major biological effects lie in inducing
      differentiation of tumor cells, arresting cell circle at G0/G1, activating cell
      apoptosis gene, enhancing the sensitivity of chemical therapy and radioactive
      therapy. So far HDAC has been an important target enzyme in anticancer drug
      research.

PMID- 16978538
TI  - Response to hepatocarcinoma Hca-F of mice immunized with heat shock protein 70
      from elemene combo tumor cell vaccine.
AB  - To analyze immune response to murine hepatocarcinoma Hca-F of mice immunized with
      heat shock protein 70 (HSP70) derived from elemene combo tumor cell vaccine (EC
      TCV) of Hca-F, HSP70 was isolated from EC-TCV by ADP affinity chromatography.
      Mice were immunized with HSP70 intraperitoneally three times and spleen cells
      were sampled. For cells, their proliferation and cytotoxicity against Hca-F were
      measured with MTT assay and their phenotypes were analyzed with flow cytometry.
      Spleen cells of immunized mice with HSP70 exhibited more potent cytotoxicity
      against Hca-F and proliferation than that of normal control mice, but less potent
      than that of mice immunized with EC-TCV. Among three groups, the percent of
      gammadeltaT lymphocytes in the mice immunized with HSP70 (35.5%) was the highest
      compared with 6.25% in normal mice, and 28.4% in the mice immunized with EC-TCV.
      Immunization of HSP70 derived from EC-TCV could elicit potent immune response to
      Hca-F. HSP70 is one of elements inducing anti-tumor immune responses against Hca
      F.

PMID- 16978539
TI  - Trichosanthin induced Th2 polarization status.
AB  - Trichosanthin is extracted from the root tuber of Chinese medicinal herb
      Trichosanthes kirilowii maximowicz (Tian Hua Fen). TCS has abortifacient, anti
      tumor, anti-HIV and immunoregulatory functions. It has been proved that it could
      inhibit immune response and arouse a T helper 2 response in the draining lymph
      node. In the current study the effect of TCS on mouse splenocytes was
      investigated. We stimulated C57BL/6 mice with TCS both in vivo and in vitro and
      analyzed the change of type 1 and type 2 cytokines in mouse splenocytes. The
      results showed that TCS could induce the expression of IL-4, one of the major T
      helper 2 (Th2) cytokines, and inhibit the expression of IFN-gamma, an important
      Th1 cytokine in spleen lymphocytes both in vivo and in vitro. It is also shown
      the kinetics of Th1-to-Th2 transition after TCS stimulation in vivo in C57BL/6
      mice. We found that type 2 cytokines, such as IL-10, TGF-beta and IL-4 were
      increased regularly but IFN-gamma was decreased at day 3 and then increased.
      However the mechanism for cytokine change is not clear.

PMID- 16978540
TI  - Imbalance of interleukin 18 and interleukin 18 binding protein in patients with
      lupus nephritis.
AB  - To evaluate the balance status of interleukin 18 (IL-18) and interleukin 18
      binding protein (IL-18BP) in circulation in patients with lupus nephritis (LN)
      and primary nephrotic syndrome (PNS), plasma levels as well as mRNA expression in
      peripheral blood mononuclear cells (PBMCs) of IL-18 and IL-18BP were measured by
      ELISA and RT-PCR respectively. The ratio of IL-18/IL-18BP was also calculated.
      Both plasma IL-18 and IL-18BP increased significantly in LN patients while only
      IL-18BP increased in PNS, which resulted in an elevated ratio of IL-18/IL-18BP in
      LN but not in PNS patients when compared with normal controls. In contrast,
      increased level of IL-18 mRNA was only detected in LN but not in PNS group,
      although IL-18BP mRNA expressions in PBMCs in both groups were higher than that
      in control. The imbalance of IL-18 and IL-18BP might be involved in the
      pathogenesis of LN, based on which a therapeutic approach is valuable to be
      developed for LN.

PMID- 16978541
TI  - [Laser treatment of port wine stain].
AB  - Laser treatment of vascular skin lesions is rapidly improving. Port wine stain
      (PWS) is one of the first lesions successfully treated with laser. The pulsed dye
      laser (PDL) has been developed on the concept of selective photothermolysis and
      has revolutionized PWS treatment. Even though the response is variable,
      substantial blanching can be obtained after several sessions. Greater selectivity
      and better response have been achieved by modifying PDL parameters such as longer
      pulse width, longer wavelength, or higher energy fluencies with cooling skin
      devices. It is known that thick, deep or raised lesions present poor response to
      conventional treatments. The aim of this study is to review the different lasers
      and other light sources which are developing for the treatment of PWS and other
      vascular lesions.

PMID- 16978542
TI  - [Bullous pemphigoid related to PUVA therapy: two further cases].
AB  - Bullous pemphigoid is an autoimmune disease that generally affects elderly people
      and is characterised by the development of subepidermal blistering. Although
      bullous pemphigoid is potentially photosensitive, its occurrence during the
      treatment course with PUVA, especially in patients with psoriasis, has
      exceptionally been described. The association of bullous pemphigoid and psoriasis
      gives rise to difficulties when initiating treatment and we consider that the use
      of methotrexate, with or without associated corticoids, is a good alternative in
      the management of such patients. We report two further cases of bullous
      pemphigoid related to PUVA therapy in patients with psoriasis.

PMID- 16978543
TI  - [Disseminated granuloma annulare located on photoexposed areas].
AB  - Granuloma annulare is a benign dermatosis of unknown etiology and chronic course,
      with different clinical variants. The disseminated form predominantly affects the
      extremities, sparing the trunk. We present the case of a 52-year-old woman with
      recurrent and autolimited outbreaks of disseminated granuloma annulare that began
      at summer time and involved the legs, arms and the dorsal area of hands. No
      pathological findings were observed in the laboratory studies performed.
      Histopathological examination confirmed our clinical suspicion. The development
      of granuloma annulare in photoexposed areas and sun exposure as a precipitating
      factor have been rarely reported in the literature.

PMID- 16978544
TI  - [Elastosis perforans serpiginosa in a patient with pseudoxanthoma elasticum].
AB  - A 34-year-old female previously diagnosed of pseudoxanthoma elasticum developed
      an annular plaque with serpiginous borders of 42 by 30 mm in diameter on the
      inner left arm. A similar lesion later appeared on the inner right arm.
      Histopathological examination of a papule showed short, fragmented, granular,
      basophilic and calcified elastic fibers in the mid-reticular dermis. The
      epidermis showed hyperplasia surrounding degenerated and normal elastic fibers.
      Transepidermal elimination channels of these elastic fibers were also observed.
      These findings were consistent with the diagnosis of elastosis perforans
      serpiginosa. Abundant multinucleated giant cells were observed surrounding the
      area of epidermal hyperplasia and in the reticular dermis. The patient was
      treated with tazarotene, and the plaques disappeared in 9 months.

PMID- 16978545
TI  - [Photocontacs dermatitis due to dexketoprofen. Report of 2 cases].
AB  - Dexketoprofen is the active isomer of ketoprofen and likewise belongs to the
      group of non-steroidal anti-inflammatory drugs (NSAIDs) derived from propionic
      acid. We have recently studied, using patch and photopatch tests, two women with
      a characteristic clinical picture of contact photodermatitis who had used topical
      dexketoprofen (Enangel) in the days before onset of the rash. In both cases we
      used the standard series of GEIDC, a series for NSAIDs, the product itself
      (Enalgel) and its excipients. On examination of the photopatches of both patients
      at 96 hours we found positive reactions to dexketoprofen and Enalgel.
      Furthermore, in one of the women we observed simultaneous photosensitivity to
      other NSAIDs and to several excipients of Enangel. Reviewing the literature we
      have found only three references on contact photodermatitis due to dexketoprofen.
      We describe two new cases, with multiple photosensitivities in one of them. We
      consider that such patients should be patch tested with dexketoprofen at 0.1-1 %
      petrolatum, concentrations that are notably inferior to those used in previous
      publications.

PMID- 16978546
TI  - [Delayed infection after Bio-alcamid implantation].
AB  - Bio-alcamid (Polymekon) is a gelatinous endoprothesis constituted of poly-alkyl
      imide and water that is used for correction of aesthetic alterations. It presents
      very good tolerance with few adverse effects. We present a case of localized
      infection in one of the sites of injection, three months after the implant was
      placed in the nasolabial furrows and lips. It would be the first case of a
      delayed infection following injection of this material, although there are few
      references in this field.

PMID- 16978547
TI  - [Palmoplantar hyperkeratosis associated with losartan].
AB  - Losartan belongs to the group of angiotensin II receptor antagonists and is used
      for the treatment of hypertension and heart failure. It acts in the renin
      angiotensin system (RAS) by blocking the angiotensin II receptor. There have been
      several reports on cutaneous side events by angiotensin antagonists due to their
      effect on the local cutaneous RAS. We review the case of palmoplantar lesions
      that developed in a patient taking losartan and the subsequent remission after
      treatment withdrawal. Since these reactions are being increasingly reported and
      as they can mimic a broad variety of classical skin disorders, they should be
      considered as the cause of sudden, inexplicable skin eruptions in patients taking
      angiotensin receptor antagonists.

PMID- 16978548
TI  - [Giant trichoblastoma].
AB  - Trichoblastoma is a benign tumour that differentiates towards the hair germ
      epithelium with a dense fibrous stroma that gives a hair bulb-like appearance.
      Currently it is being used the classification proposed by Ackerman and
      colleagues. The lesion usually presents as a solitary nodule, 1-2 cm in diameter,
      more frequently located on the scalp and face, that is easily removed during
      surgery. We describe the case of a large trichoblastoma located on the buttock.

PMID- 16978549
TI  - [Atypical pigmented penile macules].
AB  - Two patients with pigmented lesions of the penis are described. The lesions
      consisted of asymptomatic, multifocal, irregular macules, with variegated
      pigmentation. The main differential diagnostic problem was with mucocutaneous
      melanoma. Histologic examination of the lesions showed basal layer
      hyperpigmentation. No cytologic atypia of melanocytes was detectable. The
      diagnosis in both cases was melanotic macules. Because of their atypical clinical
      appearance, genital melanotic macules are often misinterpreted as mucocutaneous
      melanoma. However histopathologic study solves the problem because genital
      melanotic macules show no melanocytic proliferation nor melanocytic atypia.

PMID- 16978550
TI  - [Increase in size and change of color in a presternal pigmented lesion].

PMID- 16978551
TI  - [Acral keratotic papules].

PMID- 16978552
TI  - [Lymphangioma circumscriptum neviforme].

PMID- 16978553
TI  - [Perianal herpetic ulcers in a patient with previously undiagnosed human
      immunodeficiency virus].

PMID- 16978554
TI  - [Difficult to treat patients in primary care: are they satisfied with the care
      received in their health centre?].
AB  - OBJECTIVES: To evaluate the satisfaction of difficult to treat patients (DTP)
      cared for by a primary care team (PCT), as regards the organisational aspects and
      the care received, and to compare it with that obtained by a sample of the
      general patient population (GPP). DESIGN. Cross-sectional descriptive study.
      SETTING: Urban health centre. PARTICIPANTS: One hundred-one DTP participated,
      after being selected using Ellis and O'Dowd criteria by 8 doctors. METHOD:
      Between March and May 2004 the DTP were given self-administered anonymous
      questionnaires, prepared and validated by the Catalonian Health Institute, which
      was divided into 8 sections for their analysis. The results were compared with
      those obtained in June 2003 from a representative sample from the GPP. RESULTS: A
      total of 52 questionnaires were returned (51% participation), of which 62% were
      from women, with a mean age of 61.5+/-12.3. Average scores (0 to 10) were:
      organisation 7.2+/-1.8; (95% confidence intervale [CI], 6.6-7.7), care by the
      doctors 8.4+/-2.1 (95% CI, 7.7-9), by nurses 7.9+/-2.1 (95% CI, 7.3-8.6), by
      administrators 6.9+/-1.9 (95% CI, 6.3-7.4), care resolved 7.2+/-2 (95% CI, 6.6
      7.9), installations 7.6+/-1.7 (95% CI, 7.1-8.1), overall satisfaction 7.5+/-1.8
      (95% CI, 7-8), and total satisfaction total 7.2+/-1.6 (95% CI, 6.8-7.7). The
      91.7% (95% CI, 80-97.7) would recommend their friends to be treated in the
      centre. All the scores are higher than those in the GPP sample, with no
      statistical differences in the care by doctors and nurses sections. CONCLUSIONS:
      Although the relationships with the DTP are often problematic, the results show a
      high level of satisfaction within the DTP in all the sections evaluated, even
      higher than that of the GPP group.

PMID- 16978555
TI  - [Patients who are difficult to handle: why do we label them as such!].

PMID- 16978556
TI  - [Feeling sick and its relationship with anxiety and depression at a primary care
      emergency service].
AB  - OBJECTIVE: To study whether patients who consult because of feeling sick present
      more often with anxiety and depression disorders than the other patients using a
      rural emergency primary care service. DESIGN: Transversal descriptive study with
      paired control group. A questionnaire with clinical and social-demographic
      questions and the Goldberg Anxiety-Depression Scale (GADS) were administered,
      with uni- and bi-variate statistical analysis (P< .05). SETTING: Intensive Care
      and Emergency Unit, Baena, Cordoba, Spain. PARTICIPANTS: Sample of 166 patients
      aged between 15 and 65; 83 in the study group (SG = feeling sick) and 83 in the
      control group (CG = not feeling sick). MAIN RESULTS: The SG was positive on the
      GADS in 80.7% of cases, against the CG with 54.2% (P< .0001). Anxiety sub-scale:
      61.4% positive in SG and 42.2% in CG (P=.013). Depression sub-scale: 73.5%
      positive in SG and 47% in CG (P< .0001); 89.1% of women gave positive in the SG,
      against 64.3% of men (P=.007). Patients feeling sick who had consulted in the
      previous month (P=.039) and with a psychiatric history (P=.017) also showed a
      higher percentage of psychiatric disorders than those who did not feel sick.
      CONCLUSIONS: Patients feeling sick as their main symptom have higher prevalence
      of anxiety and depression than other patients at a rural PC emergency service.
      Being a woman, having a psychiatric history and having consulted in the previous
      month are related with these disorders.

PMID- 16978557
TI  - [Level of knowledge and action on lipaemia among Spanish primary and specialist
      care doctors. Press cholesterol study].
AB  - OBJECTIVES: To find the level of knowledge, the guidelines for action and the
      monitoring of lipaemia by Spanish primary care and specialist doctors. DESIGN AND
      INTERVENTION: A self-defined questionnaire of 12 items was designed. Data on the
      population treated and the subjective evaluation of objectives, and on the
      management and monitoring of lipid parameters were filled in. SETTING AND
      PARTICIPANTS: A total of 1998 doctors from the whole of Spain took part; 68.8% of
      the doctors interviewed worked in primary health care and 30.2% in specialist
      centres or hospitals. RESULTS: A 91% of the doctors said they followed
      international consensus on monitoring lipaemia. The most commonly used objective
      therapeutic parameter for treating lipaemia was LDL-cholesterol (83%), followed
      by total cholesterol (62%), HDL-cholesterol (56%) and triglycerides (51%). If the
      patient's lipaemia was well controlled, then 21.8% of doctors reduced the doses
      of lipid-lowerers. In general terms, no great differences were appreciated
      between the criteria followed by PC and by specialist doctors. CONCLUSIONS: The
      criteria for action on lipaemia could be improved. There are no important
      differences of view or action in clinical and therapeutic criteria for Lipaemia
      cases between PC and specialist doctors.

PMID- 16978558
TI  - [Home blood pressure self-monitoring. Influence of the mean calculation used on
      the diagnosis of white-coat hypertension].
AB  - OBJECTIVE: To describe the variations in the diagnosis performance of home blood
      pressure self-monitoring (hBPSM) with different methods for mean calculation, in
      order to diagnose white-coat hypertension (WCH). DESIGN: Multi-centre,
      descriptive, and comparative study to assess the diagnosis performance of a test
      method. SETTING: Four primary health care centres. PARTICIPANTS: A total of 157
      recently-diagnosed, untreated patients with mild-moderate hypertension took part
      in the study. METHODS: The results obtained with hBPSM (3 consecutive days with
      readings in triplicate, morning-night) were compared with a "gold standard" out
      patient blood pressure reading (OutBP). RESULTS: Systolic and diastolic BP values
      of the first day and first reading (morning-night) were higher than the remaining
      days and readings (linear trend P< .001). Results in hBPSM diagnostic performance
      using all readings to calculate the mean were: sensitivity (S), 47.6%;
      specificity (Sp), 77.4%; positive and negative predictive values (PPV and NPV),
      58.8% and 68.6%, with positive and negative probability coefficients (PPC and
      NPC), 2.10 and 0.67. When readings with greater patient alarm reaction (first day
      and first reading, morning-night) were removed, greater values of S (61.9%) were
      obtained, albeit at expense of an excessive loss in Sp (64.5%) and without
      improvement in PPC (1.74). CONCLUSIONS: The diagnostic performance of hBPSM in
      WCH was low and failed to improve with the use of different systems to calculate
      mean BP.

PMID- 16978559
TI  - [Study of the Information requirements generated by primary care doctors (ENIGMA
      Project)].
AB  - OBJECTIVES: To determine the information needs of primary care physicians by
      identifying the frequency and type of questions arising during consultation, and
      by describing the information-search pattern. DESIGN. Observational, descriptive,
      multi-centre study. SETTING: Primary care practices in Madrid, Spain.
      PARTICIPANTS: Random sample, proportionally stratified by area (urban/rural) and
      specialty (general practitioner/paediatrician), of 208 primary care physicians
      out of a total of 1182 physicians; 112 agreed to take part. INTERVENTIONS:
      Physicians consultations were video-recorded for four hours. Between patients,
      they were asked to pose all the clinical questions arising during the patient
      visit and the sources of information used to answer them. Unresolved questions
      were followed up by phone 2 weeks later to check if answers had been found and
      what sources of information had been used. Clinical questions were classified by
      topic and type. MAIN MEASUREMENTS: Number of questions posed and their answers;
      topic and type of information; information resources used. RESULTS: A total of
      3511 patient consultations, leading to 635 clinical questions, were recorded. The
      most frequent questions were on pharmacology (10%) for general practitioners, and
      infectious disease (19%) for paediatricians. The most frequent type of question
      was on the cause/interpretation of a clinical finding (44% for general
      practitioners and 48% for paediatricians). Answers to 39% of the questions were
      not sought. A 86% of the answers sought were solved, mainly using the drug
      compendium (35%) or a text-book (18%). CONCLUSIONS: Primary care physicians tried
      to resolve less than two-thirds of the questions asked, and mainly did so through
      readily available printed material. Better methods are needed to provide answers
      to questions that arise in clinical practice.

PMID- 16978560
TI  - [New medical humanism: the harmony of care].

PMID- 16978561
TI  - [Efficacy of respiratory rehabilitation on patients with moderate COPD in primary
      care and maintenance of benefits at 2 years].
AB  - OBJECTIVES: To assess the efficacy of a pulmonary rehabilitation programme
      lasting 24 months and carried out at primary care health centres in improving the
      quality of life of patients with moderate COPD, compared with a programme of 12
      weeks pulmonary rehabilitation with the usual care. Secondary aims include the
      assessment of the effects of the programme on dyspnoea, exercise capacity,
      reduction of crises, hospital admissions and length of time in hospital. DESIGN:
      Randomised clinical trial, with 3 groups in parallel and with blind evaluation.
      The control group will continue with the customary care. SUBJECT: Patients
      attended at primary health care centres with a diagnosis, based on GOLD criteria,
      of moderate COPD. Patients will be recruited from 5 health centres. 56 patients
      per group are needed (allowing for 20% drop-outs) to detect the minimum
      clinically meaningful differences between treatments, with an alpha error of
      0.005 and statistical power of 80%. INTERVENTION: All eligible patients with
      signed informed consent will be randomised into the following groups: a)
      pulmonary rehabilitation for 12 weeks and programme maintenance for 24 months; b)
      pulmonary rehabilitation for 12 weeks without maintenance programme; c) control
      group continuing with customary care. Pulmonary rehabilitation will include
      educational sessions, respiratory physiotherapy and low-intensity physical
      exercise. Follow-ups will be at the end of the rehabilitation programme, and at
      one and 2 years. MEASUREMENTS: Quality of life with the Chronic Respiratory
      Questionnaire, 6-minute walking test, Borg Dyspnoea Scale, Medical Research
      Council Dyspnoea Score, Lung Function Tests, and intervention group.

PMID- 16978562
TI  - [Involvement of the patient: the new role of patients in the health system].

PMID- 16978563
TI  - [Prevalence of osteoporosis in internal medicine out-clinics].

PMID- 16978564
TI  - [Oral anticoagulation in primary care in the province of Malaga].

PMID- 16978565
TI  - [Prescription of medicines of low therapeutic utility in primary care in Toledo
      province: variability of use].

PMID- 16978566
TI  - [Result of an intensive programme of tobacco desintoxication in primary health
      care].

PMID- 16978568
TI  - [Reflections on the feasibility and applicability of the portfolio].

PMID- 16978567
TI  - [Validity of the Framingham-REGICOR and DORICA coronary risk equations for a
      health centre's diabetic population].

PMID- 16978569
TI  - The limited value of measuring gene flow via errant pollen from GM plants.

PMID- 16978570
TI  - Hybridization between oilseed rape (Brassica napus) and different populations and
      species of Raphanus.
AB  - When cultivating genetically modified varieties, the spontaneous gene flow
      between crop and wild relatives could be of concern. We analyzed spontaneous
      hybridization between a transgenic male-sterile line of oilseed rape (Brassica
      napus, 2n = 38, AACC) and, as pollen donors, three European populations of wild
      radish (Raphanus raphanistrum, 2n = 18, Rr,Rr) and a variety of cultivated radish
      (Raphanus sativus, 2n = 18, RR). Seeds showed size and shape dimorphism that
      correlated to the frequency of hybrids. The offspring were scored morphologically
      and analyzed using DNA markers (inter-simple sequence repeats) to quantify hybrid
      frequencies. Seed set ranged from 0.4-1.2 seeds per pod, and 0.02-0.6 seeds per
      pod were confirmed as hybrids. The frequency of confirmed hybrids differed
      significantly among populations of R. raphanistrum. In the cross with a French
      population, all offspring were hybrids; in the cross with a Swiss population, 53%
      of the offspring were hybrids; and in the cross with a Danish population, only 2%
      of the offspring were found to be hybrids. The remaining offspring apparently
      belonged to two groups: the majority was B. napus-like plants, possibly of
      matromorphic origin, and a minority from the Danish cross seemed to carry
      fragments of the Raphanus genome. In the cross with a cultivated R. sativus, all
      offspring were found to be hybrids. This is the first report on spontaneous
      hybridization between B. napus and R. sativus. Hybrids from all cross
      combinations had low pollen fertility (0-15%). If R. raphanistrum occurs where
      male-sterile B. napus is cultivated, large regional differences in hybridization
      frequencies between the species could complicate environmental risk assessment of
      transgenic oilseed rape.

PMID- 16978571
TI  - The responses of crop - wild Brassica hybrids to simulated herbivory and
      interspecific competition: implications for transgene introgression.
AB  - Brassica rapa grows as a wild and weedy species throughout the world and is the
      most likely recipient of transgenes from GM oilseed rape. For transgene
      introgression to occur, the critical step which must be realized, is the
      formation of an F1 hybrid. Concerns exist that hybrid populations could be more
      vigorous and competitive compared to the parental species. This study examines
      the effect of simulated herbivory and interspecific competition on the vegetative
      and reproductive performance of non-transgenic F1 hybrids and their parental
      lines. Several vegetative and reproductive performance measures were used to
      determine the effect of simulated herbivory and competition on the Brassica
      lines, including leaf length and biomass for herbivory and seedling height and
      biomass for competition. For defoliation experiments, B. rapa showed little
      response in terms of leaf length but B. napus and the F1 hybrid responded
      negatively. Brassica rapa showed elevated biomass responses, but B. napus and the
      hybrid demonstrated negative responses to defoliation. Defoliation at the
      cotyledon stage had a slight effect upon final biomass with the F1 hybrid
      performing significantly worse than B. napus, although seed counts were not
      significantly different. For the series of competition experiments, hybrids
      seemed to be more similar to B. rapa in terms of early seedling growth and
      reproductive measures. The underperformance of hybrid plants when challenged by
      herbivory and competition, could potentially decrease survivorship and explain
      the rarity of hybrids in field surveys. However, should transgene introgression
      occur, the dynamics of hybrids could change radically thus increasing the risk of
      gene flow from a transgenic oilseed rape crop to the wild recipient.

PMID- 16978572
TI  - Spatial distribution of Aglais urticae (L.) and its host plant Urtica dioica (L.)
      in an agricultural landscape: implications for Bt maize risk assessment and post
      market monitoring.
AB  - Over the past decades, genes of Bacillus thuringiensis var. kurstaki (Berliner)
      (Bt) coding for protein toxins have been engineered into maize for protection
      against the European Corn Borer (Ostrinia nubilalis (Hbn.)). However, these
      transgenic plants may have an impact on non-target organisms. In particular, a
      potential hazard was identified for non-target lepidopteran larvae, if they
      consume Bt maize pollen on their host plants. Risk can be defined as a function
      of the effect of an event (hazard) and the likelihood of this event occurring.
      Although data on toxicity (hazard) are available from many lab and field studies,
      knowledge about the environmental exposure of European lepidopteran larvae is
      incomplete at the population level. Therefore we studied the distribution of
      small tortoiseshell caterpillars (Aglais urticae (L.)) and its host plant in an
      agricultural landscape in Germany, to estimate the potential population exposure
      to maize pollen. The results showed that larvae of the small tortoiseshell
      developed primarily on freshly sprouted nettle stands (Urtica dioica (L.)) in
      field margins, rather than adjacent to hedges and groves. However, the main
      distribution was at margins of cereal (non-maize) fields, where 70% of all larvae
      were found. This may be due the fact that cereals covered 54% of the survey area,
      while maize only covered 6.1%. On the other hand, maize fields seem so show
      higher food plant densities than cereal crops. The results must be interpreted
      carefully, as the data basis of the present study is very small, and the
      situation can vary between years due to crop rotation or other changes in
      agricultural practices. Therefore it is still questionable whether the small
      tortoiseshell is significantly exposed to maize pollen. For a conclusive risk
      assessment, more replications and surveys of larger areas in different
      intensively managed agricultural landscapes over several years are needed.

PMID- 16978573
TI  - Pyrolysis-field ionization mass spectrometry of rhizodeposits - a new approach to
      identify potential effects of genetically modified plants on soil organisms.
AB  - The objectives of the present study were (1) to investigate the qualitative
      composition of rhizodeposits leached from soils cropped with non-transgenic and
      genetically modified (GM) potatoes, and disclose if there were GM-specific
      modifications in potato rhizodeposition, and (2) to compare these results with
      conventional bulk parameters of microbial activity in soil. We have raised
      potatoes from a non-transgenic line (Solanum tuberosum L. cv. Desiree) and three
      GM lines, which expressed a gene for the resistance to kanamycin (DLH 9000) and a
      gene for T4 lysozyme (DL10 and DL12). A sandy soil placed in 340 cm3-"CombiSart"
      containers was used, from which the rhizodeposit was leached after a six-week
      growth period. The freeze-dried leachates were analyzed by pyrolysis-field
      ionization mass spectrometry (Py-FIMS). The Py-FI mass spectra gave detailed
      molecular-chemical information about the composition of leachates, indicating
      that the potato growth generally altered the composition of the soil solution.
      Moreover, a principal component analysis of the mass spectra showed differences
      between the leachates from the non-transgenic parent line and the GM potatoes as
      well as among the latter group. However, these differences in molecular
      composition could not be assigned to the release of T4-lysozyme into soil.
      Dehydrogenase activity and substrate-induced soil respiration as more common bulk
      parameters of soil microbial activity failed to disclose any significant effects
      of the various potatoes grown. The limitations of the described rhizodeposit
      leaching and analysis for risk assessment of GM potato cropping under field
      conditions are discussed critically. However, it could be concluded that the Py
      FI mass spectrometric "fingerprint" can be developed as a fast, comprehensive,
      highly sensitive and reproducible analytical approach to discern any effects GM
      crops may exert on soil ecological parameters.

PMID- 16978574
TI  - An attempt to identify recombinants between two sobemoviruses in doubly infected
      oat plants.
AB  - Recombination in RNA viruses is considered to play a major role as a driving
      force in virus variability to counterbalance loss in fitness that can be due to
      the accumulation of detrimental mutations. Studies on mixed infections are
      pertinent for understanding the role of recombination in virus evolution. They
      also provide important baseline information for studying the biosafety of plants
      expressing viral sequences. To investigate the possibility of RNA recombination
      occurrence between two sobemoviruses under little or no selection pressure, we co
      infected test plants with Cocksfoot mottle virus (CfMV) and Ryegrass mottle virus
      (RGMoV). CfMV and RGMoV were selected because of their overlapping host range and
      geographical distribution. First, symptom development of both viruses in barley
      (Hordeum vulgare) and oat (Avena sativa) was examined. Both viruses generated
      quite strong infection symptoms in oat, but synergism was not detected. RGMoV was
      lethal for barley, whereas CfMV infection in barley was nearly symptomless. RT
      PCR analysis revealed 100% infection with both viruses in oat but not in barley.
      Therefore, an RNA recombination study of CfMV and RGMoV was performed in oat. 105
      plants were co-inoculated with both viruses and putative recombinational hot spot
      regions were screened for recombination events by RT-PCR analysis at a
      sensitivity level down to 0.1-100 pg of viral genomic RNA. No recombination
      events between the two sobemoviruses were detected.

PMID- 16978575
TI  - The correlation between motoring and other types of offence.
AB  - This paper examines the link between traffic offences and criminal offences in
      Great Britain statistically by linking offence data from two national sources:
      the Driving and Vehicle Licensing Agency (DVLA) and the Home Office. A stratified
      sample of over 52,000 drivers was selected from DVLA records and matched with the
      Home Office Offenders Index. The numbers of motoring and non-motoring offences
      committed by these drivers between 1999 and 2003 were compared at various levels
      of detail. The results demonstrate the strength of the relationship between the
      number of motoring and non-motoring offences committed. For example, men who
      committed between 4 and 8 non-motoring offences committed on average 21 times as
      many serious motoring offences as men who committed no non-motoring offences, and
      3.9 times as many other motoring offences. The strongest relationship was found
      for the offence of driving while disqualified: on average, men who committed at
      least 9 non-motoring offences between 1999 and 2003 committed more than 100 times
      as many of these offences as men who committed no non-motoring offences. At the
      other extreme, the number of speeding offences was found to decrease with the
      number of non-motoring offences committed.

PMID- 16978576
TI  - Intravitreal triamcinolone acetonide for diffuse diabetic macular edema: phase 2
      trial comparing 4 mg vs 2 mg.
AB  - PURPOSE: To prospectively compare the efficacy and safety of 4 vs 2 mg
      intravitreal triamcinolone acetonide (TA) injection for diabetic macular edema.
      DESIGN: Interventional case series. METHODS:  PATIENTS: Thirty-two patients with
      diabetic macular edema unresponsive to laser photocoagulation. INTERVENTION:
      Patients were randomly assigned to receive 4 or 2 mg intravitreal TA in one eye
      (16 patients in each group). MAIN OUTCOME MEASURES: The main outcome was central
      macular thickness (CMT) measured by optical coherence tomography (OCT) at four,
      12, and 24 weeks. Secondary outcomes were gain in Early Treatment Diabetic
      Retinopathy Study (ETDRS) scores, intraocular pressure (IOP), cataract
      progression, and duration of effect. RESULTS: Before injection, mean (+/- SD) CMT
      was 564.5 +/- 119 microm and 522.9 +/- 148.5 microm in the 4- and 2-mg groups,
      respectively. At four, 12, and 24 weeks after injection, it was 275.0 +/- 79.8,
      271.4 +/- 128.7, and 448.7 +/- 146.4 microm, respectively, in the 4-mg group, and
      267.3 +/- 82.4, 289.8 +/- 111.4, and 394.7 +/- 178.9 microm, respectively, in the
      2-mg group. At no time was the difference in CMT between both groups
      statistically significant (P> 0.3). The between-group differences in the gain in
      the ETDRS score and in IOP were not statistically significant either. Diabetic
      macular edema recurred after a median period of 20 weeks vs 16 weeks in the 4-
      and 2-mg groups, respectively (P = 0.11). CONCLUSIONS: In the short term,
      intravitreal injection of 4 or 2 mg TA does not have different effects on CMT,
      visual acuity, or IOP.

PMID- 16978577
TI  - The in vitro impact of moxifloxacin and gatifloxacin concentration (0.5% vs 0.3%)
      and the addition of benzalkonium chloride on antibacterial efficacy.
AB  - PURPOSE: Varied concentrations of moxifloxacin (MOX) and gatifloxacin (GAT) and
      the addition of 0.005% benzalkonium chloride (BAK) were evaluated for eliminating
      Staphylococcus aureus (SA), Pseudomonas aeruginosa (PA), and coagulase-negative
      Staphylococcus (CNS). DESIGN: In vitro laboratory investigation. METHODS: The
      time-kill survival of SA, PA, and CNS were tested at one, two, three, six, eight,
      and 24 hours to: (1) Mueller-Hinton broth, (2) BAK, (3) 0.5% MOX, (4) 0.5% GAT,
      (5) 0.3% MOX, (6) 0.3% GAT, (7) 0.3% GAT plus BAK, (8) 0.5% MOX plus BAK, (9) 8
      microg/ml GAT, and (10) 8 mug/ml MOX. Antibiotic interactions (GAT and BAK) were
      determined by checkerboard testing. The outcome measures were (1) time-to-kill,
      (2) killing-rates, and (3) fractional inhibitory concentration (FIC) indices.
      RESULTS: MOX and GAT at either 0.5% or 0.3% had equivalent antibacterial effects.
      BAK alone or the addition of BAK to either antibiotic eliminated SA and CNS
      within one hour, whereas 0.3% GAT plus BAK eliminated bacteria faster than 0.5%
      MOX (P = .016). For PA, BAK alone had no antibacterial effect. The kill rates of
      MOX and GAT were equivalent. FIC indices indicated that GAT and BAK were
      indifferent against SA and CNS, but antagonistic to PA. CONCLUSION: As a
      preservative, MOX and GAT have equivalent antibacterial activity with similar
      killing rates. BAK appears to independently complement GAT for eliminating SA and
      CNS, but has no effect on PA. The in vitro predictive clinical effect due to
      varied antibiotic concentration and the addition of BAK requires confirmatory
      clinical studies for validation.

PMID- 16978578
TI  - Detection of competitive enzyme inhibition with end point progress curve data.
AB  - A model for a dimensionless factor, the inhibition detection limit (IDL), which
      describes the limit of detection of competitive inhibition for end point assays
      as a function of the proportion of substrate converted into product, has been
      developed. For a given end point enzymatic assay, the IDL function has a maximum
      that is dependent on the error structure parameters (four parameters) of the
      assay, the value of [S]o/K(ms), and the extent of product inhibition
      (K(ms)/K(mp)). Accordingly, the substrate conversion level that maximized the
      ability to detect samples with high Ki/[I] ratios was predicted for each member
      of a population of simulated assays. Furthermore, we identified a consensus
      substrate conversion level where the probability of a near-optimal robustness and
      detection limit for all the members of the assay population is maximal. Unlike
      the optimal substrate conversion level for individual assays, this consensus
      substrate conversion level was dependent only on [S]o/K(m), K(ms)/K(mp), and
      whether the signal increases or decreases during the course of the reaction.
      Consensus substrate conversion levels were beyond the initial velocity range for
      almost all the analyzed assay populations. It was shown that the IDL factor was a
      more informative indicator of assay quality than the popular Z' factor.

PMID- 16978579
TI  - Xanthophyll-induced aggregation of LHCII as a switch between light-harvesting and
      energy dissipation systems.
AB  - The xanthophyll cycle pigments, violaxanthin and zeaxanthin, present outside the
      light-harvesting pigment-protein complexes of Photosystem II (LHCII) considerably
      enhance specific aggregation of proteins as revealed by analysis of the 77 K
      chlorophyll a fluorescence emission spectra. Analysis of the infrared absorption
      spectra in the Amide I region shows that the aggregation is associated with
      formation of intermolecular hydrogen bonding between the alpha helices of
      neighboring complexes. The aggregation gives rise to new electronic energy
      levels, in the Soret region (530 nm) and corresponding to the Q spectral region
      (691 nm), as revealed by analysis of the resonance light scattering spectra. New
      electronic energy levels are interpreted in terms of exciton coupling of protein
      bound photosynthetic pigments. The energy of the Q excitonic level of chlorophyll
      is not high enough to drive the light reactions of Photosystem II but better
      suited to transfer excitation energy to Photosystem I, which creates favourable
      energetic conditions for the state I-state II transition. The lack of
      fluorescence emission from this energy level, at physiological temperatures, is
      indicative of either very high thermal energy conversion rate or efficient
      excitation quenching by carotenoids. Chlorophyll a fluorescence was quenched up
      to 61% and 34% in the zeaxanthin- and violaxanthin-containing samples,
      respectively, as compared to pure LHCII. Enhanced aggregation of LHCII, observed
      in the presence of the xanthophyll cycle pigments, is discussed in terms of the
      switch between light-harvesting and energy dissipation systems.

PMID- 16978580
TI  - The human beta-defensin-3, an antibacterial peptide with multiple biological
      functions.
AB  - A group of interesting molecules called defensins exhibit multiple functions but
      have been primarily recognized to possess a broad spectrum of antimicrobial
      activities. Studies have reported two different types of defensins (alpha and
      beta) from human and animals, a cyclic theta defensin from rhesus, and several
      defensin-like peptides from plants. There is no amino acid sequence homology
      between these peptides, but they all contain three Cys-Cys disulfide linkages
      while the connectivities are different. Human beta-defensin-3 (HbetaD-3) is the
      most recently discovered member of the host-defense peptide family that has
      attracted much attention. This molecule is expressed either constitutively or
      induced upon a challenge, and a growing evidence indicates the involvement of
      such molecules in adaptive immunity as well. It has been shown to exhibit
      antibacterial activities towards Gram-negative and Gram-positive bacteria as well
      as an ability to act as a chemo-attractant. Analysis of NMR structural data
      suggested a symmetrical dimeric form of this peptide in solution, which consists
      of three beta strands and a short helix in the N-terminal region. While the
      disulfide linkages are known to provide the structural stability and stability
      against proteases, the biological relevance of this dimeric form was contradicted
      by another biological study. Since there is considerable current interest in
      developing HbetaD-3 for possible pharmaceutical applications, studies to further
      our understanding on the determinants of antibacterial activities and
      immunomodulatory function of HbetaD-3 are considered to be highly significant.
      The knowledge of its biosynthetic regulation will also help in understanding the
      role of HbetaD-3 in immunity. This article presents an overview of the expression
      and regulation of HbetaD-3 in humans, and the structure-function correlations
      among HbetaD-3 and its modified peptides are discussed emphasizing the functional
      importance. The future scope for studies on HbetaD-3 and design of short potent
      antimicrobial peptides, based on the native HbetaD-3 molecule, that do not
      interfere in the immunomodulatory function is also outlined.

PMID- 16978581
TI  - Detection and phylogenic analysis of one anthrax virulence plasmid pXO1
      conservative open reading frame ubiquitous presented within Bacillus cereus group
      strains.
AB  - The presence of one of the anthrax virulence plasmid pXO1 conserved fragments was
      analyzed in 24 Bacillus cereus and B. thuringiensis strains, including 6 B.
      thuringiensis subspecies, by polymerase chain reactions. Twelve out of 24 strains
      showed PCR-positive for an ORF101 homologous sequence. Two pXO1-ORF101-like
      fragments from a B. cereus B-4ac and a commercial B. thuringiensis kurstaki HD1
      were cloned, sequenced and expressed in Escherichia coli. Toxicity assays
      revealed that the product encoded by the pXO1-ORF101-like fragment had no impact
      on either Vero cells or Chinese Hamster Ovary cells, suggesting that this
      fragment probably not contribute to enterotoxic activity. Sequence alignment of
      the pXO1-ORF101 from three Bacillus anthracis and ORF101-like fragments from
      other 12 B. cereus group isolates indicated high identity (more than 90%) and the
      presence of subgroup- and strain-specific SNPs among these fragments.

PMID- 16978583
TI  - alpha-Synuclein protects SH-SY5Y cells from dopamine toxicity.
AB  - Dopaminergic human neuroblastoma SH-SY5Y cells were stably transformed to
      increase expression of alpha-synuclein, a Parkinson's disease-related protein.
      Transformed cells were more resistant to oxidative insults, showing a
      cytoprotective role of alpha-synuclein. The expression of redox chaperonins (DJ
      1, HSP70, and 14-3-3) was evaluated by Western blotting. Expression of alpha
      synuclein reduced HSP70 levels even in the presence of dopamine, with a twofold
      increase of DJ-1 in the absence of oxidants. DJ-1 is significantly reduced by
      dopamine, and even more by dopamine and Cu(II). Increased alpha-synuclein
      expression did not affect 14-3-3, although dopamine increased its level by 60% in
      wild-type cells. alpha-Synuclein not only upregulated DJ-1, but also shifted all
      DJ-1 forms to a single spot at pI=5.7 not observed in wild-type cells. Dopamine
      gradually restored the distribution of DJ-1 forms to a situation similar to wild
      type cells, with the form at pI=6.1 progressively enriched under oxidative
      conditions.

PMID- 16978582
TI  - An array of Escherichia coli clones over-expressing essential proteins: a new
      strategy of identifying cellular targets of potent antibacterial compounds.
AB  - With the advancement of high throughput screening, it has become easier and
      faster to discover hit compounds that inhibit proliferation of bacterial cells.
      However, development in technologies used to identify cellular targets of potent
      antibacterial inhibitors has lagged behind. Here, we describe a novel strategy of
      target identification for antibacterial inhibitors using an array of Escherichia
      coli clones each over-expressing one essential protein. In a proof-of-concept
      study, eight essential genes were cloned into pLex5BA vector under the control of
      an inducible promoter. Over-expression of target proteins was confirmed. For two
      clones, one over-expressing FabI and the other over-expressing MurA enzymes, the
      host cells became 17- and 139-fold more resistant to the specific inhibitors
      triclosan and phosphomycin, respectively, while the susceptibility of other
      clones towards these inhibitors remained unchanged after induction of gene
      expression. Target identification via target protein over-expression was
      demonstrated using both mixed clone and individual clone assay formats.

PMID- 16978584
TI  - Beraprost sodium enhances neovascularization in ischemic myocardium by mobilizing
      bone marrow cells in rats.
AB  - Beraprost sodium, an orally active prostacyclin analogue, has vasoprotective
      effects such as vasodilation and antiplatelet activities. We investigated the
      therapeutic potential of beraprost for myocardial ischemia. Immediately after
      coronary ligation of Sprague-Dawley rats, beraprost (200 microg/kg/day) or saline
      was subcutaneously administered for 28 days. Four weeks after coronary ligation,
      administration of beraprost increased capillary density in ischemic myocardium,
      decreased infarct size, and improved cardiac function in rats with myocardial
      infarction. Beraprost markedly increased the number of CD34-positive cells and c
      kit-positive cells in plasma. Also, four weeks after coronary ligation of
      chimeric rats with GFP-expressing bone marrow, bone marrow-derived cells were
      incorporated into the infarcted region and its border zone. Treatment with
      beraprost increased the number of GFP/von Willebrand factor-double-positive cells
      in the ischemic myocardium. These results suggest that beraprost has beneficial
      effects on ischemic myocardium partly by its ability to enhance
      neovascularization in ischemic myocardium by mobilizing bone marrow cells.

PMID- 16978585
TI  - Expression cloning of cholesterol alpha-glucosyltransferase, a unique enzyme that
      can be inhibited by natural antibiotic gastric mucin O-glycans, from Helicobacter
      pylori.
AB  - Helicobacter pylori infects over half the world's population, but only 3% of
      those infected develop peptic ulcer, gastric cancer, and mucosa-associated
      lymphoid tissue (MALT) lymphoma. In H. pylori, alpha-glucosyl cholesterol
      constitutes more than 25% of cell wall lipids, and it has been suggested that
      alpha-glucosyl cholesterol is essential for H. pylori viability. Here, we
      identified cholesterol alpha-glucosyltransferase (CHLalphaGcT) using an
      expression cloning strategy and showed that this enzyme is distinctively
      inhibited by mucin-type O-glycans similar to those present in deeper portions of
      the gastric mucosa. Moreover, inactivation of CHLalphaGcT by homologous
      recombination led to H. pylori lethality. These results indicate that H. pylori
      CHLalphaGcT is a unique enzyme targeted by a natural antibiotic mucin and
      constitutes an excellent therapeutic target to prevent H. pylori-induced peptic
      ulcer, gastric carcinoma, and MALT lymphoma.

PMID- 16978586
TI  - Disruption of tissue plasminogen activator gene reduces macrophage migration.
AB  - Tissue plasminogen activator (tPA) is an essential component of the proteolytic
      cascade that lyses blood clots. Various studies also suggest that tPA plays
      important roles in peripheral nerve regeneration. Here we show that disruption of
      tPA gene reduces macrophage migration after sciatic nerve injury in mice.
      Moreover, lack of tPA activity attenuates migrating ability of macrophages and
      affects MMP-9 expression and activity in macrophages in vitro. Addition of
      ethylenediaminetetraacetic acid (EDTA), which inhibits MMPs, abolished the
      differences of migration ability of macrophages between tPA(+/+) and tPA(-/-)
      mice. Axonal regeneration is correlated with the increase of macrophage
      migration, suggesting that tPA may help create a beneficial environment for
      axonal regeneration through promoting macrophage infiltration. This study shows
      that tPA may play a role in nerve regeneration through regulating the migration
      ability of macrophages. This function of tPA may depend on, at least in part,
      upregulating MMP-9 expression and activity in macrophages.

PMID- 16978587
TI  - Fine mapping by genetic association implicates the chromosome 1q23.3 gene UHMK1,
      encoding a serine/threonine protein kinase, as a novel schizophrenia
      susceptibility gene.
AB  - BACKGROUND: Linkage studies by us and others have confirmed that chromosome
      1q23.3 is a susceptibility locus for schizophrenia. Based on this information,
      several research groups have published evidence that markers within both the RGS4
      and CAPON genes, which are 700 kb apart, independently showed allelic association
      with schizophrenia. Tests of allelic association with both of these genes in our
      case control sample were negative. Therefore, we carried out further fine mapping
      between the RGS4 and CAPON genes. METHODS: Twenty-nine SNP and microsatellite
      markers in the 1q23.3 region were genotyped in the United Kingdom based sample of
      450 cases and 450 supernormal control subjects. RESULTS: We detected positive
      allelic association after the eighth marker was genotyped and found that three
      microsatellite markers (p = .011, p = .014, p = .049) and two SNPs (p = .004, p =
      .043) localized in the 700 kb region between the RGS4 and CAPON genes, within the
      UHMK1 gene, were associated with schizophrenia. Tests of significance for marker
      rs10494370 remained significant following Bonferroni correction (alpha = .006)
      for multiple tests. Tests of haplotypic association were also significant for
      UHMK1 (p = .009) using empirical permutation tests, which make it unnecessary to
      further correct for both multiple alleles and multiple markers. CONCLUSIONS:
      These results provide preliminary evidence that the UHMK1 gene increases
      susceptibility to schizophrenia. Further confirmation in adequately powered
      samples is needed. UHMK1 is a serine threonine kinase nuclear protein and is
      highly expressed in regions of the brain implicated in schizophrenia.

PMID- 16978588
TI  - Distinguishing source memory and item memory: brain potentials at encoding and
      retrieval.
AB  - Vivid memory for an episode generally includes memory for a central object or
      event plus memory for background context or source information. To assess neural
      differences between source and item memory, we used event-related potentials
      (ERPs) to monitor relevant memory processes at both encoding and retrieval.
      Participants fluent in Chinese studied Chinese words superimposed on a square or
      circular background during the study phase, followed by a 1-min delay. Then,
      memory was tested for both the words (items) and the corresponding background
      (source), or, in other blocks, tested for the words alone. ERPs to study-phase
      words differed as a function of whether the word was later remembered. These Dm
      effects in the interval from 400 to 600 ms, however, did not differ according to
      whether or not source was remembered. In contrast, ERPs to test-phase words
      showed clear old/new effects that did differ across conditions. When both item
      and source were remembered accurately, old/new effects emerged earlier and were
      larger in amplitude than when source memory was either incorrect or not queried.
      These results demonstrate that encoding processes indexed by ERPs may have
      primarily reflected encoding of the visual and semantic properties of these
      words, stressing item memory over source memory. Retrieval processes indexed by
      ERPs, in contrast, likely reflected a combination of item retrieval, source
      retrieval, and related processing engaged when people were remembering words seen
      earlier.

PMID- 16978589
TI  - Overexpression of glucose transporter 2 in GT1-7 cells inhibits AMP-activated
      protein kinase and agouti-related peptide expression.
AB  - Glucose transporter 2 (GLUT2) has been proposed as a glucose sensor in pancreatic
      beta cells. GLUT2 has been found widely expressed in the brain and GLUT2 in the
      hypothalamus and hindbrain has been suggested to be involved in the central
      glucose sensing and regulation of glucose homeostasis and food intake. In this
      study, we overexpressed GLUT2 in GT1-7 neuroblastoma cells and investigated the
      effect of GLUT2 overexpression on cellular energy status in these cells. Compared
      with control cells, GLUT2 overexpression resulted in significantly increased
      cellular ATP levels at 5 and 25 mM glucose concentrations, more inhibition of
      agouti-related peptide (AgRP) mRNA and AMP-activated protein kinase (AMPK)
      phosphorylation by glucose, and attenuated stimulation of AgRP mRNA and AMPK by 2
      deoxy-d-glucose (2DG), implicating that brain GLUT2 may be important in the
      regulation of food intake.

PMID- 16978591
TI  - High expression of the mammalian X chromosome in brain.
AB  - Divergence between the sex chromosomes has led to loss and differentiation of Y
      linked genes and haplo-insufficiency for X-linked genes in males. A mechanism of
      dosage compensation, for which we recently found evidence in mammals, evolved to
      restore a balanced expression of the genome by doubling the transcriptional
      output from the X chromosome. X inactivation would then serve to avoid hyper
      transcription of X-linked genes in females by silencing one X chromosome. We also
      found that, compared to the rest of the genome, the X chromosome contains an
      excess of genes highly expressed in brain tissues. The exceptionally important
      role of the X chromosome in brain function, evident from the prevalence of X
      linked forms of mental retardation, is discussed in view of sex chromosome
      regulation and evolution and sexual reproduction.

PMID- 16978592
TI  - Effects of chronic manganese exposure on cognitive and motor functioning in non
      human primates.
AB  - Acute exposure to manganese is associated with complex behavioral/psychiatric
      signs that may include Parkinsonian motor features. However, little is known
      about the behavioral consequences of chronic manganese exposures. In this study,
      cynomolgus macaque monkeys were exposed to manganese sulfate (10-15 mg/kg/week)
      over an exposure period lasting 272+/-17 days. Prior to manganese exposure,
      animals were trained to perform tests of cognitive and motor functioning and
      overall behavior was assessed by ratings and by videotaped analyses. By the end
      of the manganese exposure period, animals developed subtle deficits in spatial
      working memory and had modest decreases in spontaneous activity and manual
      dexterity. In addition, stereotypic or compulsive-like behaviors such as
      compulsive grooming increased in frequency by the end of the manganese exposure
      period. Blood manganese levels measured at the end of the manganese exposure
      period ranged from 29.4 to 73.7 micro g/l (mean=55.7+/-10.8 (compared to levels
      of 5.1-14.2 micro g/l at baseline (mean=9.2+/-2.7)), placing them within the
      upper range of levels reported for human environmental, medical or occupational
      exposures. These results suggest that chronic exposure to levels of manganese
      achieved in this study may have detrimental effects on behavior, cognition and
      motor functioning.

PMID- 16978594
TI  - Aryl C-glycosylation of phenols with glycosyl trifluoroacetimidates.
AB  - Aryl C-glycosylation of a variety of phenols with glycosyl trifluoroacetimidates
      in the presence of TMSOTf was examined, leading to the corresponding ortho
      hydroxyaryl C-glycosides in variable yields.

PMID- 16978593
TI  - Sexual experience in female rodents: cellular mechanisms and functional
      consequences.
AB  - The neurobiology of female sexual behavior has largely focused on mechanisms of
      hormone action on nerve cells and how these effects translate into the display of
      copulatory motor patterns. Of equal importance, though less studied, are some of
      the consequences of engaging in sexual behavior, including the rewarding
      properties of sexual interactions and how sexual experience alters copulatory
      efficiency. This review summarizes the effects of sexual experience on reward
      processes and copulation in female Syrian hamsters. Neural correlates of these
      sexual interactions include long-term cellular changes in dopamine transmission
      and postsynaptic signaling pathways related to neuronal plasticity (e.g.,
      dendritic spine formation). Taken together, these studies suggest that sexual
      experience enhances the reinforcing properties of sexual behavior, which has the
      coincident outcome of increasing copulatory efficiency in a way that can increase
      reproductive success.

PMID- 16978595
TI  - Ligand-dependent and -independent degradation of the human aryl hydrocarbon
      receptor (hAHR) in cell culture models.
AB  - Studies have shown that zebrafish and rodent aryl hydrocarbon receptors (AHRs)
      are degraded following ligand exposure and that reductions in AHR protein can
      impact growth and development in vivo. The current study was designed to evaluate
      the degradation of the AHR in seven human cell lines that were derived from
      various carcinomas or from normal tissue. Consistent with studies in other
      species, the results show that the human AHR (hAHR) is degraded in a ligand
      dependent manner following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin for up
      to 16h. However, the hAHRs expressed in the various cell lines show differences
      in the time course and magnitude of degradation. The ligand dependent degradation
      is completely blocked by treatment with the proteasome inhibitor, MG-132. Ligand
      independent degradation of the hAHR following exposure to geldanamycin (GA) is
      also observed in the different cell lines, although the magnitude of hAHR
      degradation is also is variable. These findings are significant since they
      indicate that ligand-dependent and independent degradation of the AHR is a
      conserved aspect of this signal transduction cascade from fish to human. In
      addition, the study identifies several cell lines that may provide novel models
      to further assess the regulation of AHR-mediated signaling and degradation of the
      human AHR.

PMID- 16978590
TI  - Functional significance of the rapid regulation of brain estrogen action: where
      do the estrogens come from?
AB  - Estrogens exert a wide variety of actions on reproductive and non-reproductive
      functions. These effects are mediated by slow and long lasting genomic as well as
      rapid and transient non-genomic mechanisms. Besides the host of studies
      demonstrating the role of genomic actions at the physiological and behavioral
      level, mounting evidence highlights the functional significance of non-genomic
      effects. However, the source of the rapid changes in estrogen availability that
      are necessary to sustain their fast actions is rarely questioned. For example,
      the rise of plasma estrogens at pro-estrus that represents one of the fastest
      documented changes in plasma estrogen concentration appears too slow to explain
      these actions. Alternatively, estrogen can be synthesized in the brain by the
      enzyme aromatase providing a source of locally high concentrations of the
      steroid. Furthermore, recent studies demonstrate that brain aromatase can be
      rapidly modulated by afferent inputs, including glutamatergic afferents. A role
      for rapid changes in estrogen production in the central nervous system is
      supported by experiments showing that acute aromatase inhibition affects
      nociception as well as male sexual behavior and that preoptic aromatase activity
      is rapidly (within min) modulated following mating. Such mechanisms thus fulfill
      the gap existing between the fast actions of estrogen and their mode of
      production and open new avenues for the understanding of estrogenic effects on
      the brain.

PMID- 16978596
TI  - Classification of worker exposures.
AB  - The classification of jobs or workers by exposure is an important undertaking in
      any occupational epidemiological study. Hitherto, the exposure classification
      designs have been strongly motivated by a desire to generate a sufficient number
      of exposure classes for the determination of a potential exposure-response
      relationship. Thus, the partitioning of exposures has been more or less
      arbitrary. The misclassification problems created by the selection of an
      arbitrary number of exposure assignment classes have not been addressed. In any
      quantitative exposure classification scheme, specific job titles may be
      indistinguishable in existing employment records; therefore, between worker
      variability must be addressed when characterizing worker exposures. Also,
      industrial hygiene exposure measurements frequently used to characterize worker
      exposures are often treated as valid representations of exposures; but they are
      neither random nor systematic evaluations of worker exposures. As a result they
      do not represent sampling from the proper exposure stratification of workers.
      These observations suggest that the selection of exposure groups should be based
      on a more rigorous examination of the data and its limitations. Considering the
      probability of any given worker being placed into the proper class as the
      probability of finding the mean exposure for that worker within the class
      boundary, the general equations to quantify the misclassification rates for any
      classification design as well as the exposure class limits and their width for
      any acceptable misclassification rate are developed. If between worker
      variability could not be calculated from the available exposure measurements,
      then it might be estimated from the proper data compiled from the literature. By
      considering an acceptable level of exposure misclassification, it is possible to
      calculate the allowable number of exposure classes and the proper partitioning
      ratio for these classes. Thus, the trade-off between misclassification and number
      of exposure classes might be a satisfactory solution to this difficulty
      encountered in occupational epidemiology.

PMID- 16978597
TI  - Application of wavelet-based similarity analysis to epileptic seizures
      prediction.
AB  - Epileptic seizures prediction is an interesting issue in epileptology, since it
      can promise a novel approach to control seizures and understand the mechanism of
      epileptic seizures. In this paper, we describe a new method, called wavelet-based
      nonlinear similarity index (WNSI), to predict epileptic seizures using EEG
      recordings in real time. This method combines wavelet techniques and nonlinear
      dynamics. The test results of EEG recordings of rats and humans show that WNSI
      can track the hidden dynamical changes of brain electrical activity.
      Particularly, we found that it can obtain the best performance of seizure
      prediction at the beta (10-30 Hz) frequency band of EEG signals. A possible
      reason is suggested from the functional connectivity of the brain. In terms of
      this study, it is recommended that wavelet technique is very useful to improve
      the performance of epileptic seizures prediction.

PMID- 16978598
TI  - Identification and characterization of a previously undetected region between the
      perichondrium and periosteum of the developing avian limb.
AB  - In developing long bones, the growing cartilage and bone are surrounded by the
      fibrous perichondrium (PC) and periosteum (PO), respectively, which provide cells
      for the appositional growth (i.e., growth in diameter) of these tissues. Also
      during the longitudinal growth of a bone, the cartilage is continuously replaced
      by bony tissue, giving rise to the widely held assumption that the PC
      concomitantly gives rise to the PO. Except for this morphological correlate,
      however, no evidence exists for a direct conversion of PC cells to PO cells, and
      our observations presented here question this assumption. Instead, we have
      obtained evidence suggesting that a previously undescribed region exists between
      the PC and PO. This region, termed the border region (BR), has several unique
      characteristics which distinguish it from either the PC or PO, including (1) its
      lack of being determined to differentiate as either cartilage or bone, (2) its
      ability to preferentially elicit the invasion of blood vessels, and (3) its
      ability to undergo preferential growth.

PMID- 16978599
TI  - In vitro and in vivo antitumour effects of novel, orally active bile acid
      conjugated platinum complexes on rat hepatoma.
AB  - (NH3)2Pt(triacid) and (PPh3)2Pt(dehydrocholate)2 are novel bile acid-conjugated
      platinum complexes administered by oral route. The aims of the present study were
      to evaluate their in vitro cytotoxic activities on rat hepatoma cell line N1-S1,
      the in vivo antitumour effects in a syngeneic and orthotopic rat hepatoma model
      and the drug-related toxicities. Cisplatin, carboplatin and mitoxantrone were
      used as control drugs. In vitro experiments showed a concentration- and time
      dependent antiproliferative activity of bile-conjugated platinum complexes.
      (NH3)2Pt(triacid) had similar effects on cell growth of cisplatin and carboplatin
      (e.g. at 48 h, IC50 0.7+/-0.05 microM vs. 0.63+/-0.28 microM and 1.1+/-0.3
      microM, respectively; mean+/-S.D.). (NH3)2Pt(triacid) was able to inhibit tumour
      growth in a dose-dependent extent, reaching the maximum inhibitory effect at the
      80 mg/kg dose (1.95+/-0.5 g vs. 13.85+/-3.9 g of control tumour weight). By
      contrast, despite the promising in vitro antiproliferative activity,
      (PPh3)2Pt(dehydrocholate)2 showed no significant in vivo antitumour effect. The
      toxicity profile of (NH3)2Pt(triacid) resulted favourable with minimal loss of
      weight and no gastrointestinal or neurological symptoms. Instead,
      (PPh3)2Pt(dehydrocholate)2 showed dose-dependent signs of severe weight loss and
      neurological alterations. In conclusion (NH3)2Pt(triacid) is a tolerable and
      active platinum derivative endowed by a preclinical antitumour activity by oral
      route.

PMID- 16978600
TI  - Beta-endorphin differentially affects inflammation in two inbred rat strains.
AB  - It has been shown that inflammation of rat paws elicits accumulation of opioid
      peptide beta-endorphin-containing immune cells in the inflamed subcutaneous
      tissue, contributing to immunocyte-produced pain suppression. However, the
      possible mechanisms involved in the pharmacological application of beta-endorphin
      in rat paw inflammation have not been investigated. The present study was set up
      to explore the effects of intraplantar injection of beta-endorphin on
      Concanavalin A-induced paw edema in two inbred rat strains, Albino Oxford (AO)
      and Dark Agouti (DA). Both high dose-induced suppression and low dose-induced
      potentiation of edema development in AO and DA rats, respectively, were blocked
      with antagonists specific for delta (naltrindole) and kappa (nor-binaltorphimine)
      opioid receptors. beta-endorphin in vitro decreased phagocytosis and increased
      nitric oxide (NO) production in air pouch granulocytes obtained from AO rats.
      However, in cells from DA rat strain beta-endorphin modulated both phagocytosis
      and NO production in a concentration-dependent manner. It could be concluded that
      the strain-dependent opposing effects of beta-endorphin on paw inflammation are
      mediated through delta and kappa opioid receptors and probably involve changes in
      the production of reactive oxygen species by inflammatory cells. Our results
      point to the importance of genotype for pharmacological manipulations and the
      development of inflammation.

PMID- 16978601
TI  - Involvement of mu-opioid receptors in antinociception and inhibition of
      gastrointestinal transit induced by 7-hydroxymitragynine, isolated from Thai
      herbal medicine Mitragyna speciosa.
AB  - 7-hydroxymitragynine, a constituent of the Thai herbal medicine Mitragyna
      speciosa, has been found to have a potent opioid antinociceptive effect. In the
      present study, we investigated the mechanism of antinociception and the
      inhibitory effect on gastrointestinal transit of 7-hydroxymitragynine, and
      compared its effects with those of morphine. When administered subcutaneously to
      mice, 7-hydroxymitragynine produced antinociceptive effects about 5.7 and 4.4
      times more potent than those of morphine in the tail-flick (ED50=0.80 mg/kg) and
      hot-plate (ED50=0.93 mg/kg) tests, respectively. The antinociceptive effect of 7
      hydroxymitragynine was significantly blocked by the mu1/mu2-opioid receptor
      antagonist beta-funaltrexamine hydrochloride (beta-FNA) and the mu1-opioid
      receptor-selective antagonist naloxonazine in both tests. Thus, 7
      hydroxymitragynine acts predominantly on mu-opioid receptors, especially on mu1
      opioid receptors. Isolated tissue studies further supported its specificity for
      the mu-opioid receptors. Further, 7-hydroxymintragynine dose-dependently
      (ED50=1.19 mg/kg, s.c.) and significantly inhibited gastrointestinal transit in
      mice, as morphine does. The inhibitory effect was significantly antagonized by
      beta-FNA pretreatment, but slightly antagonized by naloxonazine. The ED50 value
      of 7-hydroxymitragynine on gastrointestinal transit was larger than its
      antinociceptive ED50 value. On the other hand, morphine significantly inhibits
      gastrointestinal transit at a much smaller dose than its antinociceptive dose.
      These results suggest that mu-opioid receptor mechanisms mediate the
      antinociceptive effect and inhibition of gastrointestinal transit. This compound
      induced more potent antinociceptive effects and was less constipating than
      morphine.

PMID- 16978602
TI  - Prostacyclin therapy increases right ventricular capillarisation in a model for
      flow-associated pulmonary hypertension.
AB  - Pulmonary hypertension, and consequently right ventricular failure, complicates
      several congenital heart defects. Although intervention in the prostacyclin
      thromboxane ratio is known to improve outcome, the underlying mechanism is not
      clear. Therefore, effects of acetyl salicylic acid and iloprost are studied in an
      animal model for flow-associated pulmonary hypertension. Male Wistar rats with
      flow-associated pulmonary hypertension, an aortocaval shunt in addition to
      monocrotaline induced pulmonary hypertension, were treated with low-dose aspirin
      (25 mg/kg/day) or iloprost (72 microg/kg/day). Effects on pulmonary hemodynamics
      and pulmonary vascular remodeling as well as right ventricular hemodynamics and
      remodeling were evaluated. Ninety percent (n=7/8) of the untreated pulmonary
      hypertensive rats developed dyspnea and pleural fluid, whereas this was seen in
      50% (n=4/8, ns) and 10% (n=1/8, P<0.05 vs. untreated animals) of the aspirin and
      iloprost-treated rats, respectively. This could not be attributed to changes in
      pulmonary artery pressure, wall-lumen ratio of the pulmonary vasculature or right
      ventricular hypertrophy. However, both therapies restored reduced right
      ventricular capillary to myocyte ratio in pulmonary hypertensive rats (0.95+/
      0.10 in untreated rats vs. 1.38+/-0.18 in control animals; P<0.05, and 1.32+/
      0.11 in aspirin-treated and 1.29+/-0.9 in iloprost-treated rats; both P<0.05 vs.
      non-treated animals), which was associated with improved right ventricular
      contractility (iloprost). Thus, interventions in the prostacyclin-thromboxane
      metabolism improve outcome in rats with flow-associated pulmonary hypertension.
      However, these effects may be attributed to effects on cardiac rather than on
      pulmonary vascular remodeling.

PMID- 16978603
TI  - The location of photodegradable nitric oxide store in the mouse stomach fundus.
AB  - The aim of this study was to investigate the location of photodegradable nitric
      oxide (NO) store using a pharmacological approach in mouse gastric fundus. The
      ultraviolet light irradiation (UV; 360 nm, 60 s), electrical field stimulation
      (EFS; 4 Hz, 25 V, 1 ms, 15s-train), exogenous nitric oxide (NO; 10 microM),
      nitroglycerin (100 microM) and isoproterenol (5 nM) induced relaxation in mouse
      gastric fundus preparations in the absence or presence of an intact mucosa. The
      NO scavenger, haemoglobin (20 microM), significantly inhibited the relaxation of
      intact and denuded mucosa stomach fundus to UV light irradiation, EFS and NO, but
      not to nitroglycerin and isoproterenol. The superoxide anion generator,
      pyrogallol (50 microM), inhibited relaxation of intact and denuded mucosa stomach
      fundus induced by UV light irradiation, EFS, NO, but not to nitroglycerin and
      isoproterenol. The inhibition observed with pyrogallol was prevented by exogenous
      Cu/Zn superoxide dismutase (SOD; 100 U/ml), a membrane impermeable antioxidant.
      The Cu/Zn SOD inhibitor, diethyldithiocarbamic acid (DETCA; 8 mM), inhibited the
      relaxation of intact and denuded mucosa stomach fundus to UV light irradiation,
      EFS, NO and nitroglycerin but not those to isoproterenol. Exogenous SOD (100
      U/ml) partially prevented the inhibitory effect of DETCA on relaxation to UV
      light irradiation, EFS, NO but not to nitroglycerin. DETCA-induced inhibition of
      the nitroglycerin-induced relaxation was partially prevented by the cell
      permeable polyethylene-glycol-superoxide dismutase (100 U/ml). These results
      indicate that photodegradable NO store is, at least in part, unlikely to be
      within smooth muscle cells, and furthermore, that UV light-induced relaxation is
      not dependent on gastric mucosal layer.

PMID- 16978604
TI  - The novel histone deacetylase inhibitor BML-210 exerts growth inhibitory,
      proapoptotic and differentiation stimulating effects on the human leukemia cell
      lines.
AB  - Histone deacetylase inhibitors have a potent role in the strategy for the
      treatment of leukemias. BML-210 (N-(2-Aminophenyl)-N' phenyloctanol diamine) is
      the novel histone deacetylase inhibitor, and its mechanism of action has not been
      characterized. In this study, we examined the in vitro effects of BML-210 on the
      human leukemia cell lines (NB4, HL-60, THP-1, and K562). We found that BML-210
      inhibits the growth of all cell lines and promotes apoptosis in a dose- and time
      dependent manner. BML-210 alone induces HL-60 and K562 cell differentiation (up
      to 30%) to granulocytes and erythrocytes, respectively, and in combination with
      differentiation agents - all-trans retinoic acid and hemin, markedly potentates
      it. Those treatments cause G1 arrest and histone H4 acetylation, affects
      transcription factor NF-kappaB and Sp1 binding activity to their consensus
      sequences, the p21 or the FasL promoters, and influences expression of Sp1, NF
      kappaB, p21 and FasL. These findings suggest that BML-210 could be a promising
      antileukemic agent to induce apoptosis and to modulate differentiation through
      the modulation of histone acetylation and gene expression.

PMID- 16978605
TI  - Effects of chronic ethanol administration on brain protein levels: a proteomic
      investigation using 2-D DIGE system.
AB  - The effects of chronic ethanol treatment on the brain proteome were investigated
      in the long-fin striped strain of zebrafish Danio rerio. Prolonged exposure to
      0.5% (v/v) ethanol resulted in the development of tolerance to the ethanol
      induced disruption of normal swimming behavior. This behavioral tolerance was
      manifested after two weeks of continuous treatment and was maintained for an
      additional three weeks. After four weeks of ethanol treatment, zebrafish brains
      were divided into 40,000 g supernatant and pellet fractions, and an Ettan 2-D
      fluorescence difference gel electrophoresis (DIGE) system was used to detect
      ethanol-induced alterations in the level of protein expression. Protein
      identification was carried out using matrix assisted laser desorption ionization
      time of flight (MALDI-TOF) mass spectrometry and the Mascot and ProFound search
      engines. In the present study, we have identified some novel protein targets as
      well as substantiated some putative previous targets of chronic ethanol exposure.

PMID- 16978607
TI  - Extracellular HIV-1 Nef increases migration of monocytes.
AB  - Infiltration of human immunodeficiency virus type 1 (HIV-1)-infected and
      uninfected monocytes/macrophages in organs and tissues is a general phenomenon
      observed in progression of acquired immunodeficiency syndrome (AIDS). HIV-1
      protein Nef is considered as a progression factor in AIDS, and is released from
      HIV-1-infected cells. Here, we show that extracellular Nef increases migration of
      monocytes. This effect is (i) concentration-dependent, (ii) reaches the order of
      magnitude of that induced by formyl-methyonyl-leucyl-proline (fMLP) or CC
      chemokine ligand 2 (CCL2)/monocyte chemotactic protein (MCP)-1, (iii) inhibited
      by anti-Nef monoclonal antibodies as well as by heating, and (iv) depends on a
      concentration gradient of Nef. Further, Nef does not elicit monocytic THP-1 cells
      to express chemokines such as CCL2, macrophage inhibitory protein-1alpha (CCL3)
      and macrophage inhibitory protein-1beta (CCL4). These data suggest that
      extracellular Nef may contribute to disease progression as well as HIV-1
      spreading through affecting migration of monocytes.

PMID- 16978606
TI  - Quantitative assessment of local collagen matrix remodeling in 3-D culture: the
      role of Rho kinase.
AB  - The purpose of this study was to quantitatively assess the role of Rho kinase in
      modulating the pattern and amount of local cell-induced collagen matrix
      remodeling. Human corneal fibroblasts were plated inside 100-microm thick
      fibrillar collagen matrices and cultured for 24 h in media with or without the
      Rho kinase inhibitor Y-27632. Cells were then fixed and stained with phalloidin.
      Fluorescent (for f-actin) and reflected light (for collagen fibrils) 3-D optical
      section images were acquired using laser confocal microscopy. Fourier transform
      analysis was used to assess collagen fibril alignment, and 3-D cell morphology
      and local collagen density were measured using MetaMorph. Culture in serum
      containing media induced significant global matrix contraction, which was
      inhibited by blocking Rho kinase (p<0.001). Fibroblasts generally had a bipolar
      morphology and intracellular stress fibers. Collagen fibrils were compacted and
      aligned parallel to stress fibers and pseudopodia. When Rho kinase was inhibited,
      cells had a more cortical f-actin distribution and dendritic morphology. Both
      local collagen fibril density and alignment were significantly reduced (p<0.01).
      Overall, the data suggests that Rho kinase-dependent contractile force generation
      leads to co-alignment of cells and collagen fibrils along the plane of greatest
      resistance, and that this process contributes to global matrix contraction.

PMID- 16978608
TI  - TGFbeta1-induced aortic endothelial morphogenesis requires signaling by small
      GTPases Rac1 and RhoA.
AB  - TGFbeta is a potent regulator of cell differentiation in many cell types. On
      aortic endothelial cells, TGFbeta1 displays angiogenic properties in inducing
      capillary-like tube formation in collagen I gels, in vitro. We investigated
      cytoskeletal changes that precede tube formation and related these alterations to
      the effects of TGFbeta1 on the activation state of members of the RhoGTPase
      family. TGFbeta1 promotes cell elongation and stress fiber formation in aortic
      endothelial cells. Using cell lines with inducible expression of Rac1 mutants, we
      show that these events are mimicked by expression of dominant-negative Rac1
      whereas the constitutively active mutant prevents the TGFbeta1-mediated change of
      phenotype. Although TGFbeta1 induces an initial rise in the Rac1-GTP content,
      this phase is followed by a prolonged loss of the active form. In contrast, RhoA
      activity increases progressively and reaches a plateau when Rac1-GTP is no longer
      detectable. Prolonged inhibition of Rac1 appears necessary and sufficient for the
      increase in RhoA-GTP. In situ examination of Rho activity in TGFbeta1-treated
      cells provides evidence that active RhoA relocalizes to the tips of elongated
      cells. Inhibiting the Rho effector ROCK abrogates tube formation. Thus, Rac1 and
      RhoA are regulated by TGFbeta1 in the process of endothelial tube formation in
      collagen I gels.

PMID- 16978609
TI  - Activation of 5-HT4 receptors inhibits secretion of beta-amyloid peptides and
      increases neuronal survival.
AB  - Activation of 5-HT4 receptors has been shown to improve memory processes in
      preclinical cognition models, suggesting potential utility of 5-HT4 agonists for
      the symptomatic treatment of Alzheimer's disease (AD). Recent studies have shown
      that 5-HT4 agonists also increase the secretion of the non-amyloidogenic soluble
      amyloid precursor protein-alpha (sAPPalpha). In the present study, we
      demonstrated that a selective 5-HT4 partial agonist, RS67333, inhibited the
      generation of beta-amyloid peptide (Abeta) in primary cortical cultures of Tg2576
      transgenic mice expressing human APP(K670N/M671L). Furthermore, treatments with
      RS67333 selectively increased the survival of transgenic neurons in a dose
      dependent manner, which was inhibited by 5-HT4 antagonists. These and previous
      data collectively suggest that the 5-HT4 receptor may be an effective therapeutic
      target for AD, providing both symptomatic improvements and neuroprotection.

PMID- 16978610
TI  - Acanthamoeba: could it be an environmental host of Shigella?
AB  - Shigellosis is a serious public health problem in Korea, because large outbreaks
      of Shigella sonnei infections were recorded in many parts of the country during
      the period 1998-2000. However, the epidemiological features of shigellosis are
      not well known. In this study, we devised conditions suitable for the growth and
      replication of Shigella in an amoebic intracellular environment, and investigate
      whether medium conditions affect the survival and replication of Shigella within
      Acanthamoeba. We evaluated the uptake rates of invasive and non invasive S.
      sonnei strains by three Acanthamoeba species, namely, A. castellanii Neff, A.
      astronyxis Ray & Hayes, and A. healyi OC-3A. When A. castellanii Neff was
      infected with S. sonnei 99OBS1 or 80DH248, shigellae was maintained for a longer
      time in cytoplasms than in other Acanthamoeba species. S. sonnei 99OBS1 strain (a
      virulent strain) was recovered in higher numbers than the non-virulent S. sonnei
      80DH248 strain in all experiments. Moreover, S. sonnei was more easily engulfed
      by Acanthamoeba at 18 degrees C. The shigellae uptake rates of Neff strain, which
      was cultured in free-media (less nutrition), were higher (>10-fold) than those
      observed in original amoeba culture media (PYG medium) in all time points. S.
      sonnei 99OBS1 was localized, with an intact membrane, to the vacuoles of
      Acanthamoeba. We conclude that free-living amoebae more likely act as
      environmental hosts for shigellae, and thus, may have contributed to outbreaks of
      shigellosis in Korea.

PMID- 16978612
TI  - Fen1 does not control somatic hypermutability of the (CTG)(n)*(CAG)(n) repeat in
      a knock-in mouse model for DM1.
AB  - The mechanism of trinucleotide repeat expansion, an important cause of
      neuromuscular and neurodegenerative diseases, is poorly understood. We report
      here on the study of the role of flap endonuclease 1 (Fen1), a structure-specific
      nuclease with both 5' flap endonuclease and 5'-3' exonuclease activity, in the
      somatic hypermutability of the (CTG)(n)*(CAG)(n) repeat of the DMPK gene in a
      mouse model for myotonic dystrophy type 1 (DM1). By intercrossing mice with Fen1
      deficiency with transgenics with a DM1 (CTG)(n)*(CAG)(n) repeat (where 104n110),
      we demonstrate that Fen1 is not essential for faithful maintenance of this repeat
      in early embryonic cleavage divisions until the blastocyst stage. Additionally,
      we found that the frequency of somatic DM1 (CTG)(n)*(CAG)(n) repeat instability
      was essentially unaltered in mice with Fen1 haploinsufficiency up to 1.5 years of
      age. Based on these findings, we propose that Fen1, despite its role in DNA
      repair and replication, is not primarily involved in maintaining stability at the
      DM1 locus.

PMID- 16978613
TI  - Geranylgeranyl-pyrophosphate (GGPP) synthase is down-regulated during
      differentiation of osteoblastic cell line MC3T3-E1.
AB  - Isoprenylation of geranylgeranyl-pyrophosphate (GGPP) is critical for activation
      of small GTPases. We examined the roles of GGPP synthase (GGPPS) during the
      differentiation induced by the cell-to-cell contact in osteoblastic cell line
      MC3T3-E1 cells. We found that (1) both mRNA and protein expression of GGPPS was
      reduced with decrement of its activity during the differentiation, (2) GGOH,
      which is converted to GGPP in the cells, inhibited differentiation. These results
      suggest that the decrement of GGPP is critical for the cell-to-cell contact
      induced differentiation, in which the down-regulation of GGPPS might be involved.

PMID- 16978614
TI  - Circulating levels of total angiopoietin-2 and the soluble Tie-2 receptor in
      women during ovarian stimulation and early gestation.
AB  - Circulating levels of Ang-2 and sTie-2 receptor were detectable but invariant in
      women during COS cycles. During the postimplantation period, the rise in Ang-2
      (but not sTie-2) levels probably reflects placental rather than luteal
      production.

PMID- 16978615
TI  - Ultrasound characteristics and histological dating of the endometrium in a
      natural cycle in infertile women compared with fertile controls.
AB  - OBJECTIVE: To compare endometrial dating and ultrasound texture in a natural
      cycle before IVF and relate these to outcome and to fertile references. DESIGN:
      Prospective study with a fertile reference group. SETTING: Four university IVF
      clinics. PATIENT(S): Seventy-five IVF patients and 21 fertile women.
      INTERVENTION(S): Ultrasound, biopsy, blood sampling. In vitro fertilization-ET in
      the following cycle. MAIN OUTCOME MEASURE(S): Endometrial evaluation, P, IVF
      outcome. RESULT(S): At day LH+7, 42% infertile vs. 67% fertile women demonstrated
      endometria that were in phase (statistically nonsignificant difference). Nine
      percent had an accelerated endometrium, and 47% (infertile) vs. 24% (fertile) had
      a delayed endometrium (statistically nonsignificant difference). Statistically
      significantly fewer women with tubal factor and no hydrosalpinges had an
      endometrium in phase (20%) than was the case in fertile women (67%). Dating could
      not predict outcome. Statistically significantly more women in the hydrosalpinx
      group had a visible midline at day LH+7 compared with the case in other infertile
      groups. Forty-three percent conceived after IVF-ET. Plasma P was statistically
      significantly lower in nonpregnant women compared with in women with ongoing
      pregnancies and with fertile controls. A periovulatory hyperechogenic endometrium
      resulted in no ongoing pregnancies. CONCLUSION(S): In a natural cycle preceding
      IVF, a low midluteal P level predicts a low implantation rate. A periovulatory
      hyperechogenic endometrium or hydrosalpinges visible at ultrasound may have some
      predictive value. Endometrial dating was of no help.

PMID- 16978616
TI  - Association of cytochrome P450 1B1 polymorphism with first-trimester miscarriage.
AB  - OBJECTIVE: To determine whether the cytochrome P450 1B1 (CYP1B1) Val432Leu
      polymorphism is associated with risk of miscarriage. We also analyzed the
      possible interaction between this polymorphism and caffeine intake. DESIGN: The
      population-based case-control study included 507 women with miscarriage in the
      first trimester of pregnancy and 908 controls with a normal first-trimester
      pregnancy. The controls were frequency matched to cases. The material was
      analyzed taking maternal age, smoking habits, alcohol intake, caffeine intake,
      fetal karyotype, nausea, and vomiting into consideration. SETTING: University
      hospital and primary care facility. MAIN OUTCOME MEASURE(S): CYP1B1 Val432Leu
      genotype frequencies in cases and controls. RESULT(S): Carriers of the CYP1B1 432
      Val/Val genotype were at a higher risk of miscarriage in the first trimester of
      pregnancy (odds ratio = 1.46; 95% confidence interval, 1.02-2.08). We also found
      a significant interaction between genotype and caffeine intake. CONCLUSION(S):
      CYP1B1 Val432Leu polymorphism is associated with first-trimester miscarriage, and
      it may also modify the risk among coffee drinkers.

PMID- 16978617
TI  - Day 3 compared with day 2 cryopreservation does not affect embryo survival but
      improves the outcome of frozen-thawed embryo transfers.
AB  - A retrospective study was performed to determine the differences in embryo
      survival and frozen-thawed embryo transfers outcome between cryopreservation
      performed on day 3 versus day 2. We conclude that freezing supernumerary embryos
      on day 3 provides similar thawing survival parameters, better implantation,
      pregnancy, and live-birth rates compared with day 2 cryopreservation.

PMID- 16978618
TI  - Early compaction on day 3 may be associated with increased implantation
      potential.
AB  - OBJECTIVE: To determine whether day 3 embryos exhibiting early compaction have an
      improved implantation potential compared to embryos without compaction. DESIGN: A
      retrospective cohort study. SETTING: Hospital-based academic medical center.
      PATIENT(S): Women <38 years of age undergoing IVF cycles between November 2001
      and December 2004 having a day 3 transfer of one or two embryos with >8 cells.
      INTERVENTION(S): Standard IVF protocol. MAIN OUTCOME MEASURE(S): Compaction
      grading and implantation rates of 1,047 embryos as related to fragmentation of
      >or= 8-cell embryos in patients with either 0% or 100% implantation. RESULT(S):
      Compaction grading was strongly associated with implantation potential; however,
      the direction of this effect depended on the degree of fragmentation. In embryos
      with <10% fragmentation, implantation rates increased with the degree of
      compaction (grade 1, 25%; grade 2, 33%; and grade 3, 47%); in embryos with
      >or=10% fragmentation, the effect was reversed (grade 1, 38%; grade 2, 20%; and
      grade 3, 9%). CONCLUSION(S): Assessing the degree of compaction can be a valuable
      addition to traditional morphologic assessment in identifying optimal embryos for
      transfer on day 3.

PMID- 16978619
TI  - Comparison of the efficacy of the aromatase inhibitor letrozole and clomiphene
      citrate as adjuvants to recombinant follicle-stimulating hormone in controlled
      ovarian hyperstimulation: a prospective, randomized, blinded clinical trial.
AB  - OBJECTIVE: To study the efficacy of the aromatase inhibitor letrozole as adjuvant
      to recombinant FSH (rFSH) in controlled ovarian hyperstimulation (COH). DESIGN:
      Prospective, randomized, and blinded clinical study. SETTING: Academic tertiary
      institute. PATIENT(S): Forty-one patients with unexplained infertility undergoing
      intrauterine insemination (IUI) therapy were randomized to receive either
      letrozole or clomiphene citrate (CC) as adjuvants to rFSH. INTERVENTION(S): From
      day 3 to 7 of the cycle 2.5 mg/d letrozole or 100 mg/d CC were administrated. All
      patients received 75 IU rFSH starting on day 7 of stimulation until the day of
      hCG administration. Ovulation was triggered with recombinant hCG (250 microg)
      when the leading follicle(s) reached 18 mm in diameter. A single IUI was
      performed 36 hours later. The luteal phase was supplemented with micronized
      progesterone vaginally. MAIN OUTCOME MEASURE(S): Ovarian stimulation response
      (E(2) levels and number of follicles) was our primary outcome. RESULT(S): There
      were no differences in demographic characteristics between groups. Although there
      was a significantly lower peak serum E(2) level in the group receiving letrozole
      + rFSH compared with CC + rFSH (914 +/- 187 vs. 1,207 +/- 309 pg/mL,
      respectively; P<.007), there were no differences in the number of mature (>16 mm)
      preovulatory follicles. A significantly higher endometrial thickness was observed
      at the time of hCG administration in patients that received letrozole (9.5 +/-
      1.5 mm vs. 7.3 +/- 1.1 mm; P=.0001). The clinical pregnancy rate was similar
      between groups (23.8% vs. 20%, respectively). CONCLUSION(S): The aromatase
      inhibitor letrozole appears to constitute a good alternative to CC in patients
      with unexplained infertility undergoing gonadotropin-stimulated COH cycles
      combined with IUI therapy.

PMID- 16978620
TI  - Quality of reporting of test accuracy studies in reproductive medicine: impact of
      the Standards for Reporting of Diagnostic Accuracy (STARD) initiative.
AB  - OBJECTIVE: To evaluate the extent to which test accuracy studies published in two
      leading reproductive medicine journals in the years 1999 and 2004 adhered to the
      Standards for Reporting of Diagnostic Accuracy (STARD) initiative parameters, and
      to explore whether the introduction of the STARD statement has led to an improved
      quality of reporting. DESIGN: Structured literature search. Articles that
      reported on the diagnostic performance of a test in comparison with a reference
      standard were eligible for inclusion. For each article we scored how well the 25
      items of the STARD checklist were reported. These items deal with the study
      question, study participants, study design, test methods, reference standard,
      statistical methods, reporting of results, and conclusions. We calculated the
      total number of reported STARD items per article, summary scores for each STARD
      item, and the average number of reported STARD items per publication year.
      SETTING: Not applicable. PATIENT(S): Not applicable. INTERVENTION(S): Not
      applicable. MAIN OUTCOME MEASURE(S): Quality of reporting. RESULT(S): We found 24
      studies reporting on test accuracy in reproductive medicine in 1999 and 27
      studies in 2004. The mean number of reported STARD items for articles published
      in 1999 was 12.1 +/- 3.3 (range 6.5-20) and 12.4 +/- 3.2 (range 7-17.5) in 2004,
      after publication of the STARD statement. Overall, less than half of the studies
      reported adequately on 50% or more of the STARD items. The reporting of
      individual items showed a wide variation. There was no significant improvement in
      mean number of reported items for the articles published after the introduction
      of the STARD statement. CONCLUSION(S): Authors of test accuracy studies in the
      two leading fertility journals poorly report the design, conduct, methodology,
      and statistical analysis of their study. Strict adherence to the STARD guidelines
      should be encouraged.

PMID- 16978621
TI  - Antimullerian hormone and pituitary gland activity after prolonged down
      regulation with goserelin acetate.
AB  - The size of the pool of growing follicles was normal after prolonged down
      regulation, as indicated by normal AMH levels 4 and 8 weeks after goserelin
      administration. However, there was a profound down-regulation of LH levels;
      therefore we suggest administration of exogenous LH to proceed to IVF or
      alternatively stimulation of endogenous LH secretion with daily administration of
      GnRH agonist. These need to be assessed prospectively.

PMID- 16978622
TI  - Relationship between delay of surgical diagnosis and severity of disease in
      patients with symptomatic deep infiltrating endometriosis.
AB  - We investigated relationships between delay of surgical diagnosis and severity of
      disease in 95 patients with symptomatic deep infiltrating endometriosis. The
      delay before surgical diagnosis of deep infiltrating endometriosis was
      significantly longer for patients with advanced stage IV (revised American
      Society for Reproductive Medicine [ASRM] score >70) disease than for those with
      stage I, II, III, or IV (revised ASRM score <or=70) disease.

PMID- 16978623
TI  - Cryopreservation of the ovary by vitrification as an alternative to slow-cooling
      protocols.
AB  - OBJECTIVE: To study the thermal properties of a cryoprotectant solution, called
      VS4, and of VS4-impregnated whole sheep ovaries with pedicle. DESIGN: Physical
      and experimental animal study. SETTING: Academic research environment. ANIMAL(S):
      Five- to 6-month-old ewes. INTERVENTION(S): Thermal properties on cooling of a
      cryoprotectant solution called VS4 were measured by differential scanning
      calorimetry. VS4 contains 2.75 mol/L dimethyl sulfoxide, 2.76 mol/L formamide,
      and 1.97 mol/L propylene glycol. Whole sheep ovaries were collected at the
      slaughterhouse and prepared for a vitrification procedure. Cortex and vessels
      underwent histologic examination before and after vitrification, and the thermal
      properties of VS4-impregnated ovarian cortex were then studied. MAIN OUTCOME
      MEASURE(S): Critical cooling rates (V(ccr)), vitreous transition temperature
      (Tg), end-of-melting temperature (Tm), follicle viability assessment by trypan
      blue test, and histologic examination of ovary and vessel structure. RESULT(S):
      The critical cooling rate (V(ccr)) of VS4 solution was estimated to be 14.3 +/-
      1.1 degrees C/min. Its vitreous transition temperature (Tg) was -125.2 +/- 0.2
      degrees C, and its end-of-melting temperature (Tm) -34.3 +/- 0.1 degrees C.
      Following our vitrification procedure, immediate follicle viability was 61.4% +/-
      2.2%. The percentage of normal primordial follicles remaining after vitrification
      was 48% +/- 3.8%. The V(ccr) of VS4-impregnated cortex could not be determined
      because of the quantity of ice forming as of the top programmed cooling rate (
      300 degrees C/min). The mean ovarian cortex cooling rate actually attained
      experimentally during vitrification was -342.9 +/- 49.6 degrees C/min.
      CONCLUSION(S): Vitrification of entire organs, such as ovaries, is a great
      challenge in cryobiology and reproductive medicine. Physical studies seem
      indispensable for progress with this technique. Thus, our ovarian perfusion
      procedure needs improving to enhance ovarian cortex impregnation and bring down
      the V(ccr) rate in both tissue and VS4 solution.

PMID- 16978624
TI  - Increased vaginal oxidative stress, apoptosis, and inducible nitric oxide
      synthase in a diabetic rat model: implications for vaginal fibrosis.
AB  - OBJECTIVE: To determine whether vaginal fibrosis occurs in diabetic animals and
      is associated with oxidative stress and cell death and with the expression of
      inducible nitric oxide synthase (iNOS), as a putative antifibrotic mechanism.
      DESIGN: Research experimental project. SETTING: University research laboratory.
      ANIMAL(S): Female Wistar rats. INTERVENTION(S): Female rats were injected with
      streptozotocin or saline and killed at 3 months. The vaginas were excised and
      processed for paraffin-embedded sections (n = 6 per group) or were frozen for
      biochemical and molecular biology procedures. MAIN OUTCOME MEASURE(S):
      Immunohistochemistry and quantitative image analysis were applied to tissue
      sections to measure alpha-smooth muscle actin, transforming growth factor beta1,
      plasminogen activator inhibitor, NOS isoforms, Cu/Zn superoxide dismutase,
      apoptotic index, and nitrotyrosine. Xanthine dehydrogenase, reactive oxygen
      species (ROS), and hydroxyproline were measured in fresh vaginal tissue (n = 5
      per group). Reactive oxygen species also were determined in blood. RESULT(S):
      Diabetes was associated with vaginal fibrosis, as evidenced by increased
      collagen, transforming growth factor beta1, plasminogen activator inhibitor, and
      apoptosis, and by decreased alpha-smooth muscle actin. The increment of ROS and
      the reduction of superoxide dismutase indicated oxidative stress in diabetic
      tissue, accompanied by iNOS induction and increased nitric oxide-ROS reaction.
      CONCLUSION(S): Diabetes in the rat causes oxidative stress and fibrosis in the
      vagina, which may be compensated partially by iNOS induction to reduce ROS.

PMID- 16978626
TI  - mRNA expression patterns for GH, PRL, SL, IGF-I and IGF-II during altered feeding
      status in rabbitfish, Siganus guttatus.
AB  - Feeding time is a major synchronizer of many physiological rhythms in many
      organisms. Alteration in the nutritional status, specifically fasting, also
      affects the secretion rhythms of growth hormone (GH) and insulin-like growth
      factor-I (IGF-I). In this study, we investigated whether the expression patterns
      for the mRNAs of GH, prolactin (PRL) and somatolactin (SL) in the pituitary
      gland, and insulin-like growth factor I and II (IGF-I and IGF-II) in the liver of
      juvenile rabbitfish (Siganus guttatus) follow a rhythm according to feeding time
      and whether these hormone rhythms changes with starvation. Hormone mRNA levels
      were determined by real time PCR. The daily expression pattern for the mRNAs of
      GH, PRL and SL was not altered whether food was given in the morning (10:00 h) or
      in the afternoon (15:00 h). The daily GH mRNA expression pattern, however, was
      affected when food was not available for 3 days. In contrast, the daily
      expression pattern for IGF-I mRNA reaches its peak at roughly 5-6h after feeding.
      This pattern, however, was not observed with IGF-II mRNA. During 15-day
      starvation, GH mRNA levels in starved fish were significantly higher than the
      control fish starting on the 9th day of starvation until day 15. The levels
      returned to normal after re-feeding. In contrast to GH, PRL mRNA levels in
      starved fish were significantly lower than the control group starting on the 6th
      day of starvation until 3 days after re-feeding. SL mRNA levels were not
      significantly different between the control and starved group at anytime during
      the experiment. Both IGF-I and IGF-II mRNA levels in starved group were
      significantly higher than the control fish on the 3rd and 6th day of starvation.
      mRNA levels of both IGF-I and II in the starved fish decreased starting on the
      9th day of starvation. While IGF-I mRNA levels in the starved group continued to
      decrease as starvation progressed, IGF-II mRNA levels were not significantly
      different from the control during the rest of the starvation period. The results
      indicate that aside from GH and IGF-I, PRL and IGF-II are likewise involved in
      starvation in rabbitfish.

PMID- 16978625
TI  - Successful pregnancies after transplantation of frozen-thawed mouse ovaries into
      chimeric mice that received lethal-dose radiation.
AB  - OBJECTIVE: To study whether fecundity was recovered in mice into which umbilical
      cord blood cells (UCBCs) were transfused after lethal-dose radiation, followed by
      transplantation of frozen-thawed ovaries. DESIGN: Prospective basic research
      study. SETTING: Academic research laboratory. ANIMAL(S): Female C57BL/6 mice as
      recipients of UCBCs and ovaries, male B6C3F1 mice for mating, and green
      fluorescent protein (GFP)-transgenic mice: 18.5-day-old fetuses (-/+) for UCBCs
      and adult GFP mice (+/+) for ovarian tissues. INTERVENTION(S): The UCBCs were
      transfused into each irradiated mouse, with GFP+ ovaries transplanted 4 weeks
      later. The chimeric mice were mated 3 weeks after ovarian transplantation and
      were examined 14 to 16 weeks after the transfusion of UCBCs. MAIN OUTCOME
      MEASURE(S): Percentage of chimerism, number of GFP+ pups. RESULT(S): The
      percentage of chimerism in these mice tends to increase with the radiation dose.
      The recovery of fecundity was observed in the chimeric mice that were
      transplanted with fresh and previously vitrified ovaries after exposure to
      radiation. CONCLUSION(S): Even when the exposure dose of radiation administered
      as pretreatment is lethal, the fecundity of recipients can be maintained if their
      ovaries are cryopreserved before they are exposed to radiation.

PMID- 16978627
TI  - Publication rate of Trauma abstracts presented at an International Orthopaedic
      conference.
AB  - INTRODUCTION: Oral presentations at major conferences are often used to present
      new material and generate discussion. However, conference abstracts that
      ultimately fail to be published are of little use to the wider medical community.
      The aim of this study was to evaluate the publication rate of trauma papers
      presented at an international orthopaedic conference, and to assess the factors
      which predict publication. METHODS: All abstracts presented orally at the trauma
      sessions of the European Federation of National Associations of Orthopaedics and
      Traumatology (EFORT) Congresses in 1999 (Belgium) and 2001 (Greece) were
      assessed. A MEDLINE and EMBASE search was performed to identify articles written
      by the first, second and last authors of each abstract to identify a matching
      journal article. Subspecialty, country of origin of abstract, study type, journal
      of publication and publication year were tabulated. RESULTS: Two hundred and
      seventy eight trauma abstracts were presented orally, and 112 (40.3%) achieved
      subsequent publication. Abstracts on fractures of the proximal femur were the
      most common (18.7%) and had one of the highest rates of publication (44.2%).
      Greece and the UK provided the largest number of abstracts, and randomised trials
      were the study type with the highest rate of publication (80.0%). Thirty two
      percent of journal articles appeared within 1 year of the conference and 63%
      within 2 years. Injury was the journal most likely to publish the articles.
      CONCLUSION: About 60% of Trauma abstracts presented did not result in a
      subsequent full-text publication. The citation of conference proceedings should
      be discouraged, and clinicians should be wary of implementing information gleaned
      from conference presentations into their clinical practice.

PMID- 16978628
TI  - "What's in a name?" The indiscriminate use of the "Quality of life" label, and
      the need to bring about clarity in conceptualizations.

PMID- 16978629
TI  - Challenges for future nursing research: providing evidence for health-care
      practice.

PMID- 16978630
TI  - Gender differences in behavioural changes induced by latent toxoplasmosis.
AB  - There is growing evidence that the protozoan Toxoplasma gondii modifies behaviour
      of its intermediate hosts, including humans, where it globally infects about 20
      60% of the population. Although it is considered asymptomatic in its latent
      stage, it was previously found to have remarkable and gender different effects on
      the personality factors A (warmth), G (rule consciousness), L (vigilance,
      mistrust) and Q3 (self-control, self-image) from Cattell's 16PF Questionnaire. We
      performed a double blind experiment testing 72 and 142 uninfected men and women,
      respectively, and 20 and 29 infected men and women, respectively, in order to
      verify these gender differences using behavioural experiments. Our composite
      behavioural variables Self-Control and Clothes Tidiness (analogue to the 16PF
      factors G--conscientiousness and Q3--self-control) showed a significant effect of
      the toxoplasmosis-gender interaction with infected men scoring significantly
      lower than uninfected men and a trend in the opposite direction in women. The
      effect of the toxoplasmosis-gender interaction on our composite behavioural
      variable Relationships (analogue to factor A--warmth) approached significance;
      infected men scored significantly lower than uninfected men whereas there was no
      difference in women. In the composite behavioural variable Mistrust (analogue to
      factor L), the pattern was affected by environment (rural versus urban). Possible
      interpretations of the gender differences are discussed.

PMID- 16978631
TI  - Chlamydial lipopolysaccharide is present in serum during acute coronary syndrome
      and correlates with CRP levels.
AB  - Infections, Chlamydia pneumoniae as a major candidate, have been suggested to
      participate in inflammatory processes ultimately leading to atherosclerosis. In
      the present study we measured serum levels of chlamydial lipopolysaccharide
      (cLPS) and highly sensitive C-reactive protein (hsCRP) in the acute coronary
      syndrome (ACS) patients (n=145). During ACS, both cLPS and hsCRP were elevated
      and significant correlation (P=0.003, r=0.25) between them was observed. Both
      cLPS and hsCRP levels decreased after the event and correlation remained
      significant during the follow-up period. Our results suggest that cLPS is
      liberated from the damaged tissue persistently infected with C. pneumoniae during
      the ACS event. The significant correlation between cLPS and hsCRP levels further
      point to the possibility that both levels reflect the magnitude of tissue damage.

PMID- 16978632
TI  - Predictors of carotid atherosclerotic plaque progression as measured by
      noninvasive magnetic resonance imaging.
AB  - The purpose of this in vivo MRI study was to quantify changes in atherosclerotic
      plaque morphology prospectively and to identify factors that may alter the rate
      of progression in plaque burden. Sixty-eight asymptomatic subjects with >or=50%
      stenosis, underwent serial carotid MRI examinations over an 18-month period.
      Clinical risk factors for atherosclerosis, and medications were documented
      prospectively. The wall and total vessel areas, matched across time-points, were
      measured from cross-sectional images. The normalized wall index (NWI=wall
      area/total vessel area), as a marker of disease severity, was documented at
      baseline and at 18 months. Multiple regression analysis was used to correlate
      risk factors and morphological features of the plaque with the rate of
      progression/regression. On average, the wall area increased by 2.2% per year
      (P=0.001). Multiple regression analysis demonstrated that statin therapy (P=0.01)
      and a normalized wall index >0.64 (P=0.001) were associated with a significantly
      reduced rate of progression in mean wall area. All other documented risk factors
      were not significantly associated with changes in wall area. Findings from this
      study suggest that increased normalized wall index and the use of statin therapy
      are associated with reduced rates of plaque progression amongst individuals with
      advanced, asymptomatic carotid atherosclerosis.

PMID- 16978633
TI  - Uniformly-sized, molecularly imprinted polymers for nicotine by precipitation
      polymerization.
AB  - Uniformly-sized, molecularly imprinted polymers (MIPs) for (S)-nicotine have been
      prepared by a precipitation polymerization method using methacrylic acid (MAA) or
      2-(trifluoromethyl)acrylic acid (TFMAA) as a functional monomer and
      divinylbenzene (DVB) as a cross-linker in a mixture of toluene and acetonitrile.
      The (S)-nicotine-imprinted MAA-co-DVB polymers were monodispersed microspheres of
      about 4 microm in diameter, while the TFMAA-co-DVB ones were gel-like. Molecular
      recognition abilities of the former MIPs were evaluated for nicotine and its
      structurally related compounds in liquid chromatography using a mixture of sodium
      phosphate buffer and acetonitrile as the eluent. Enantioseparation of nicotine
      was attained using the (S)-nicotine-imprinted MAA-co-DVB polymers. Furthermore,
      they could selectively trap nicotine in cigarette smoke extracts.

PMID- 16978634
TI  - Simultaneous determination of bisphenol A and its halogenated derivatives in
      river water by combination of isotope imprinting and liquid chromatography-mass
      spectrometry.
AB  - A restricted access media-molecularly imprinted polymer (RAM-MIP) for
      [2H16]bisphenol A (BPA-d16) was prepared by a multi-step swelling and
      polymerization method using 4-vinylpyridine as a functional monomer and ethylene
      glycol dimethacrylate as a cross-linker, followed by hydrophilic surface
      modification using glycerol dimethacrylate and glycerol monomethacrylate as
      hydrophilic monomers. The obtained RAM-MIP showed excellent molecular recognition
      abilities for BPA and BPA-d6 as well as BPA-d16 used as the template molecule,
      and good ones for tetrachlorobisphenol A (Cl4-BPA) and tetrabromobisphenol A (Br4
      BPA). Next, the RAM-MIP was utilized for selective on-line pretreatment and
      enrichment of BPA, Cl4-BPA and Br4-BPA in a river water sample, followed by their
      separation and determination by LC-MS. The calibration graphs of BPA, Cl4-BPA and
      Br4-BPA, constructed using BPA-d6 as an internal standard, showed good linearity
      in the range of 12.5-200 pg/mL (r > 0.999) with a 2-mL injection of a river water
      sample. The inter-day precision data for the assay of BPA, Cl4-BPA and Br4-BPA at
      25 pg/mL were 1.08, 3.67 and 1.58%, respectively. Furthermore, this method was
      successfully applied for the simultaneous determination of BPA and its
      halogenated derivatives in river water.

PMID- 16978635
TI  - pH transitions in cation exchange chromatographic columns containing weak acid
      groups.
AB  - Complex pH transitions occur in cation exchange columns used for protein
      chromatography during equilibration and salt elution steps when the stationary
      phase contains weak acid groups even if the mobile phase is buffered and the
      buffering species do not interact with the stationary phase. In this work, we
      present a local equilibrium model to predict the magnitude and duration of these
      pH transients. The model equations are solved by the method of characteristics
      and by numerical simulations using an equilibrium-dispersive model. By
      incorporating an explicit description of the dissociation of the weakly ionogenic
      groups in the resin, we show that counterion binding in the column can be
      predicted for different buffer systems based on a single experimental resin
      titration curve without having to resort to empirically defined adsorption
      equilibrium constants. Model predictions based on these assumptions are found to
      be in excellent agreement with experimental results obtained for three different
      resins containing varying concentrations of weak acid groups. Four common buffer
      systems, acetate, citrate, MES, and phosphate are considered with both step and
      gradient changes in salt concentration at pH 5.5. Each buffer yields a different
      pH excursion behavior. We demonstrate that when the counterion concentration is
      kept constant in each of these buffers, which is needed to attain identical
      protein adsorption behavior, the magnitude of the pH transitions occurring during
      salt steps is nearly independent of the buffer system. On the other hand, the
      duration of the pH transitions is smallest for MES suggesting that this buffer
      system is preferable where pH variations are to be prevented.

PMID- 16978636
TI  - Comparison of dye adsorption by mesoporous hybrid gels: understanding the
      interactions between dyes and gel surfaces.
AB  - Without using any templating agents, mesoporous hybrid gels were prepared using
      mixtures of tetraethoxysilane (TEOS) with n-propyltriethoxysilane (PTES),
      bis(trimethoxysilyl)hexane (TSH), or bis(trimethoxysilylpropyl)amine (TSPA) as
      precursors. Fourier transform infrared (FTIR), N2 adsorption/desorption,
      thermogravimetry (TG), point of zero charge (PZC), and water vapor adsorption
      measurements were used to characterize the gels. The adsorption of methyl orange
      (MO), methyl red (MR), bromocresol purple (BP), phenol red (PR), neutral red
      (NR), and brilliant blue FCF (BBF) by the gels in both 0.01 M HCl and 0.01 M NaOH
      solutions was compared comprehensively. The gel derived from TEOS/TSH (with 
      (CH2)6- groups, Gel 2) has the largest specific surface area (695 m2 g(-1)), the
      smallest pore volume (0.564 cm3 g(-1)), and the smallest average pore size (3.7
      nm). The gels derived form TEOS/PTES (with -(CH2)2CH3 groups, Gel 1), and
      TEOS/TSPA (with -(CH2)3NH(CH2)3- groups, Gel 3) have similar textual properties.
      The PZC of Gels 1, 2, and 3 was estimated to be 6.28, 6.20, and 6.88,
      respectively. Gel 3 has the highest PZC due to the presence of -NH- groups. In
      general, Gel 2 shows the highest dye adsorption among all the gels in both acidic
      and basic solutions. All the dyes except NR have much lower adsorption in basic
      solutions than in acidic solutions. In acidic solutions Gels 1 and 2 have similar
      adsorption trends for the dyes, except for BP, with NR having the highest
      adsorption, and PR the lowest adsorption. Gel 3 presents a different trend from
      Gels 1 and 2, with BBF having the highest adsorption, and MR the lowest
      adsorption. In basic solutions the order of dye adsorption by all the gels is
      shown to follow the sequence NR>>MR approximately BBF>MO>BP approximately PR. The
      adsorption results can be explained by considering the textural properties of the
      gels and the interactions between the gel surfaces and the dyes, which include
      hydrogen bonding, electrostatic, and hydrophobic interactions.

PMID- 16978637
TI  - Determination of the surface energy of kaolinite and serpentine using PACHA
      formalism-comparison with immersion experiments.
AB  - Clays play an important role in a wide variety of industrial processes. Indeed,
      they present interesting surface properties. For these reasons, we study the
      surface energy of models of clays by solid state calculations using
      electronegativities equalization. In this article, we focus on kaolinite and
      serpentine, two clays characterized by a simple structure of the TO type. We
      describe the clays and their structures and we develop a simple model from solid
      state calculations used to determine the surface energy. The results are in
      agreement with a recent interpretation of the immersion of kaolinite in water.
      This article must be related to some others focusing on solid surface energy,
      especially some treating talc and chlorites, and montmorillonites saturated by
      alkaline cations, to be published.

PMID- 16978638
TI  - Deposition of nanosized latex particles onto silica and cellulose surfaces
      studied by optical reflectometry.
AB  - Deposition of positively charged nanosized latex particles onto planar silica and
      cellulose substrates was studied in monovalent electrolyte solutions at pH 9.5.
      The deposition was probed in situ with optical reflectometry in a stagnation
      point flow cell. The surface coverage can be estimated reliably with island film
      theory as well as with a homogeneous film model, as confirmed with atomic force
      microscopy (AFM). The deposition kinetics on the bare surface was of first order
      with respect to the particle concentration, whereby the deposition rate was close
      to the value expected for a perfect collector. The efficiency coefficient, which
      was defined as the ratio of the experimental and theoretical deposition rate
      constants, was in the range from 0.3 to 0.7. Subsequently, the surface saturated
      and a limiting maximum coverage was attained (i.e., blocking). These trends were
      in qualitative agreement with predictions of the random sequential absorption
      (RSA) model, where electrostatic interactions between the particles were
      included. It was observed, however, that the substrate strongly influenced the
      maximum coverage, which was substantially higher for silica than for cellulose.
      The major conclusion of this work was that the nature of the substrate played an
      important role in a saturated layer of deposited colloidal particles.

PMID- 16978639
TI  - Application of the maximum bubble pressure technique for dynamic surface tension
      studies of surfactant solutions using the Sugden two-capillary method.
AB  - Exact knowledge of the dead time as part of the bubble lifetime in the maximum
      bubble pressure method is an important prerequisite for accurate dynamic surface
      tension measurements. The duration of the dead time depends essentially on the
      capillary geometry and affects significantly the measured surface tensions of
      concentrated surfactant solutions. Increase of the dead time leads to a
      significant surface tension decrease of a freshly formed bubble surface due to
      the significantly higher residual adsorption of the surfactant molecules. It is
      shown that correct dynamic surface tensions are obtained with the experimental
      procedure of Sugden's method only when in addition to the fixed frequency of
      bubble formation, also the dead time values for the two capillaries are kept
      constant.

PMID- 16978640
TI  - Measuring word learning: dynamic versus static assessment of kindergarten
      vocabulary.
AB  - This preliminary study investigated the potential of using a dynamic approach to
      assessing expressive word mapping. Because measuring word mapping with productive
      language responses is much more difficult than measuring receptive word mapping,
      incorporating a dynamic measure allowed us to tap partial mapping and provided
      useful information on word learning. Participants were 24 typically developing
      African American children, from high-risk backgrounds and low-risk backgrounds,
      as determined by school and family demographics. Performance was compared on the
      PPVT-III and on the dynamic assessment of word mapping. The dynamic assessment of
      word mapping provided information about complete and partial mapping of words.
      Additionally, there was an interaction between risk and performance on the
      vocabulary and word learning measures. These data suggest that the use of the
      dynamic measure in conjunction with traditional vocabulary measures may have the
      potential to provide an estimate of word-learning ability. LEARNING OUTCOMES:
      Readers will (1) be able to identify the need for word-learning measures and (2)
      become familiar with the combined technique of using dynamic assessment and fast
      mapping.

PMID- 16978641
TI  - Biochemical analysis of a DNA replication origin in the archaeon Aeropyrum
      pernix.
AB  - We have characterised the interaction of the Aeropyrum pernix origin recognition
      complex proteins (ORC1 and ORC2) with DNA using DNase I footprinting. Each
      protein binds upstream of its respective gene. However, ORC1 protein alone
      interacts more tightly with an additional region containing multiple origin
      recognition box (ORB) sites that we show to be a replication origin. At this
      origin, there are four ORB elements disposed either side of an A+T-rich region.
      An ORC1 protein dimer binds at each of these ORB sites. Once all four ORB sites
      have bound ORC1 protein, there is a transition to a higher-order assembly with a
      defined alteration in topology and superhelicity. Furthermore, after this
      transition, the A+T-rich region becomes sensitive to digestion by DNase I and P1
      nuclease, revealing that the transition promotes distortion of the DNA in this
      region, presumably as a prelude to loading of MCM helicase.

PMID- 16978642
TI  - Crystal structure of an RNA quadruplex containing inosine tetrad: implications
      for the roles of NH2 group in purine tetrads.
AB  - Polyinosinic acid has been known to adopt the four-stranded helical structure but
      its basic unit, inosine tetrad (I tetrad), has not been determined at the atomic
      level. Here we report the crystal structure of an RNA quadruplex containing an I
      tetrad at 1.4 A resolution. The I tetrad has one cyclic hydrogen bond N1...O6
      with the bond length of 2.7 A. A water bridge is observed in the minor groove
      side of the base tetrad. Even though it is sandwiched by guanine tetrads (G
      tetrads), the I tetrad is buckled towards the 3' side of the tetrad plane, which
      results from the different interaction strength with K ions on two sides of the
      tetrad plane. Comparison with both G tetrad and adenine tetrad indicates that
      lack of NH2 in the C2 position makes the I tetrad prone to buckle for
      interactions with ligands. Two U*(G-G-G-G) base pentads are observed at the
      junction of the 5' termini of two quadruplexes. The uridine residue in the base
      pentad is engaged in two hydrogen bonding interactions (N2(G)-H...O2(U) and
      O2'(G)-H...O4(U)) and a water-mediated interaction (N3(G) and N3(U)) with the G
      tetrad. We also discuss the roles of amino group in purine tetrads and the inter
      quadruplex interactions in RNA molecules. These quadruplexes may interact with
      each other by stacking, groove binding and intercalation.

PMID- 16978643
TI  - Structural and functional studies of EpsC, a crucial component of the type 2
      secretion system from Vibrio cholerae.
AB  - The type 2 secretion system (T2SS) occurring in Gram-negative bacteria is
      composed of 12-15 different proteins which form large assemblies spanning two
      membranes and secreting several virulence factors in folded state across the
      outer membrane. The T2SS component EpsC of Vibrio cholerae plays an important
      role in this machinery. While anchored in the inner membrane, by far the largest
      part of EpsC is periplasmic, containing a so-called homology region (HR) domain
      and a PDZ domain. Here we report studies on the structure and function of both
      periplasmic domains of EpsC. The crystal structures of two variants of the PDZ
      domain of EpsC from V. cholerae were determined at better than 2 A resolution.
      Compared to the short variant, the longer variant contains an additional N
      terminal helix, and reveals a significant difference in the position of helix
      alphaB with respect to the beta-sheet. Both our structures show that the PDZ
      domain of EpsC adopts a more open form than in previously reported structures of
      other PDZ domains. Most interestingly, in the crystals of the short EpsC-PDZ
      domain the peptide binding groove interacts with an alpha-helix from a
      neighboring subunit burying approximately 921 A2 solvent accessible surface. This
      makes it possible that the PDZ domain of this bacterial protein binds proteins in
      a manner which is altogether different from that seen in any other PDZ domain so
      far. We also determined that the HR domain of EpsC is primarily responsible for
      the interaction with the secretin EpsD, while the PDZ is not, or much less, so.
      This new finding, together with studies of others, leads to the suggestion that
      the PDZ domain of EpsC may interact with exoproteins to be secreted while the HR
      domain plays a key role in linking the inner-membrane sub-complex of the T2SS in
      V. cholerae to the outer membrane secretin.

PMID- 16978644
TI  - The crystal structure of an ADP complex of Bacillus subtilis pyridoxal kinase
      provides evidence for the parallel emergence of enzyme activity during evolution.
AB  - Pyridoxal kinase catalyses the phosphorylation of pyridoxal, pyridoxine and
      pyridoxamine to their 5' phosphates and plays an important role in the pyridoxal
      5' phosphate salvage pathway. The crystal structure of a dimeric pyridoxal kinase
      from Bacillus subtilis has been solved in complex with ADP to 2.8 A resolution.
      Analysis of the structure suggests that binding of the nucleotide induces the
      ordering of two loops, which operate independently to close a flap on the active
      site. Comparisons with other ribokinase superfamily members reveal that B.
      subtilis pyridoxal kinase is more closely related in both sequence and structure
      to the family of HMPP kinases than to other pyridoxal kinases, suggesting that
      this structure represents the first for a novel family of "HMPP kinase-like"
      pyridoxal kinases. Moreover this further suggests that this enzyme activity has
      evolved independently on multiple occasions from within the ribokinase
      superfamily.

PMID- 16978645
TI  - Point mutations in protein globular domains: contributions from function,
      stability and misfolding.
AB  - Several contrasting hypotheses have been formulated about the influence of
      functional and conformational properties, like stability and avoidance of
      misfolding, on the evolution of protein globular domains. Selection at functional
      sites has been suggested to be detrimental to stability or coupled to it.
      Avoidance of misfolding may be achieved by discarding misfolding-prone sequences
      or by maintaining a stable native state and thus destabilizing partially or fully
      unfolded states from which misfolding can take place. We have performed a
      hierarchical analysis of a large database of point mutations to dissect the
      relative contributions of function, stability and misfolding in the evolution of
      natural sequences. We show that at catalytic sites, selection for function
      overrules selection for stability but find no evidence for an anticorrelation
      between function and stability. Selection for stability plays a secondary role at
      binding sites, but is not fully coupled to selection for function. Remarkably, we
      did not find a selective pressure against misfolding-prone sequences in globular
      proteins at the level of individual positions. We suggest that such a selection
      would compromise native-state stability due to a correlation between the
      stabilities of native and misfolded states. Stabilization of the native state is
      the most frequent way in which natural proteins avoid misfolding.

PMID- 16978646
TI  - Early protein evolution: building domains from ligand-binding polypeptide
      segments.
AB  - It has been suggested that in the early evolution of proteins, segments of
      polypeptide, unable to fold in isolation, may have collapsed together to form
      folded proto-domains. We wondered whether the incorporation of segments with a
      pre-existing binding activity into a folded domain could, by fixing the ligand
      binding conformation and/or providing additional contacts, lead to large affinity
      improvements and provide an evolutionary advantage. As a model, we took a segment
      of polypeptide from hen egg lysozyme that in the native protein forms the binding
      interface with the monoclonal antibodies HyHEL5 and F10 (KD=60 pM). When
      expressed in bacteria the isolated segment was unfolded, readily proteolysed and
      only bound weakly to the antibodies (KD>1 microM). We then combined the segment
      with random genomic segments to create a repertoire of chimaeric polypeptides
      displayed on filamentous bacteriophage. By use of proteolysis (to select folded
      polypeptide) and anti-lysozyme antibodies (to select an active conformation) we
      isolated a folded dimeric protein with an enhanced antibody affinity (KD=400 pM).
      Unexpectedly the dimer also incorporated a single heme molecule (KD=33 nM) that
      stabilised the dimer (Tm=59 degrees C with heme, 35 degrees C without heme).
      These results show that the binding affinities of flexible polypeptide segments
      can be greatly enhanced on protein folding, and that the folding can be
      stabilised by prosthetic groups. This supports the hypothesis that sub-domain
      polypeptide segments with functional activities may have contributed to domain
      creation in early evolution.

PMID- 16978647
TI  - In vitro evolution of a hyperstable Gbeta1 variant.
AB  - An in-vitro selection strategy was used to obtain strongly stabilized variants of
      the beta1 domain of protein G (Gbeta1). In a two-step approach, first candidate
      positions with a high potential for stabilization were identified in Gbeta1
      libraries that were created by error-prone PCR, and then, after randomization of
      these positions by saturation mutagenesis, strongly stabilized variants were
      selected. For both steps the in-vitro selection method Proside was employed.
      Proside links the stability of a protein with the infectivity of a filamentous
      phage. Ultimately, residues from the two best selected variants were combined in
      a single Gbeta1 molecule. This variant with the four mutations E15V, T16L, T18I,
      and N37L showed an increase of 35.1 degrees C in the transition midpoint and of
      28.5 kJ mol(-1) (at 70 degrees C) in the Gibbs free energy of stabilization. It
      was considerably more stable than the best variant from a previous Proside
      selection, in which positions were randomized that had originally been identified
      by computational design. Only a single substitution (T18I) was found in both
      selections. The best variants from the present selection showed a higher
      cooperativity of thermal unfolding, as indicated by an increase in the enthalpy
      of unfolding by about 60 kJ mol(-1). This increase is apparently correlated with
      the presence of Leu residues that were selected at the positions 16 and 37.

PMID- 16978648
TI  - Effect of flumazenil-augmentation on microsleep and mood in depressed patients
      during partial sleep deprivation.
AB  - The antidepressive effect of sleep deprivation (SD) in depressed patients
      disappears after sleep of the recovery night and after early morning naps. Both
      can provoke a rapid relapse into depression in SD-responders. In addition, the
      occurrence of short episodes of sleep (termed microsleep, MS) during partial SD
      (PSD) is associated with SD-nonresponse, suggesting that MS during the time awake
      may be related to relapse or PSD-nonresponse. The GABA-benzodiazepine receptor
      antagonist flumazenil augments vigilance and reduces NonREM-sleep pressure in
      early morning recovery sleep in volunteers after SD. Therefore, in this study 27
      patients with major depression were subjected to a PSD. In a double blind
      randomized design either flumazenil or placebo was orally applied during PSD in
      order to examine whether the application of flumazenil reduces sleep propensity
      and thus, increases antidepressant efficacy of PSD. EEG was registered
      continuously for 60h by a portable device for the assessment of microsleep
      episodes at baseline and during PSD. Flumazenil application significantly
      suppressed frequency and total amount of MS. While the antidepressant efficacy of
      PSD was not different between flumazenil and placebo during PSD, the subjective
      mood improved after the recovery night in patients treated with flumazenil. It is
      concluded that GABAergic mechanisms are involved in the regulation of MS during
      PSD, which may be related to a mood stabilizing effect after the recovery night.
      However, the mechanisms underlying the association between the occurrence of MS
      during PSD and mood variation have to be further clarified.

PMID- 16978649
TI  - The association of insomnia with anxiety disorders and depression: exploration of
      the direction of risk.
AB  - The purpose of this study is to explore the direction of the association between
      insomnia and anxiety disorders and major depression among a community-based
      sample of adolescents to better understand their potential etiologic
      relationships. Data come from a community-based sample of 1,014 youth aged 13-16.
      Structured interviews were conducted to assess DSM-IV diagnoses. Retrospectively
      reported ages of onset were used in Proportional Hazards models to estimate
      increased risk of one disorder associated with prior onset of the others. The
      lifetime associations of DSM-IV insomnia with each anxiety disorder and with
      depression were moderate (OR=3.2-6.8). Among those with comorbid disorders,
      anxiety disorders preceded insomnia 73% of the time, while insomnia occurred
      first in 69% of comorbid insomnia and depression cases. Any prior anxiety
      disorder was associated with an increased risk of insomnia adjusting for gender,
      race/ethnicity, and depression prior to insomnia (HR=3.5). However, prior
      insomnia was not significantly associated with onset of anxiety disorders. Prior
      depression was not associated with onset of insomnia, but prior insomnia was
      associated with onset of depression adjusting for gender, race/ethnicity, and any
      prior anxiety disorder (HR=3.8). These results suggest distinct natural courses
      of development between DSM-IV insomnia, anxiety, and depression during
      adolescence. Additionally insomnia may have independent, and potentially
      etiologically distinct, directional associations with anxiety disorders versus
      depression.

PMID- 16978650
TI  - Peptide YY reverses TNF-alpha induced transcription factor binding of interferon
      regulatory factor-1 and p53 in pancreatic acinar cells.
AB  - BACKGROUND: Cytokine activation in the pancreatitis induces local and systemic
      cellular damage. Transcription factors interferon regulatory factor-1 (IRF-1) and
      the tumor suppressor gene p53 collaborate to enhance p21 related cell cycle
      regulation during pathological disease progression. However, little is known
      about their role in the pancreas after cytokine challenge. Our laboratory has
      previously shown that TNF-alpha induces the binding of many transcription
      factors, including NF-kappa B, and treatment with the gut hormone, Peptide YY
      (PYY), ameliorates the effects. We hypothesized that TNF-alpha would induce IRF-1
      and p53 protein binding in pancreatic acinar cells and that PYY would attenuate
      the effect. MATERIALS AND METHODS: Rat pancreatic acinar AR42J cells were treated
      with rat recombinant TNF-alpha (200 ng/ml). To verify that our model was inducing
      pancreatitis, alpha-amylase activity was measured in the cell culture supernatant
      by fluorescence spectroscopy. PYY [3-36] was added at 500 pM 30 min post-TNF
      treatment; cells were harvested at 2 h for extraction of nuclear protein.
      Transcription factor binding of IRF-1 and p53 were determined by protein/DNA
      array analysis using chemiluminescence detection, and relative spot densities
      were measured by densitometry. A two-fold increase or decrease in density was
      considered significant. RESULTS: Amylase enzyme activity was significantly (P <
      0.05) elevated in the TNF-alpha-treated cells by 2 h. Protein/DNA array analysis
      revealed significant up-regulation of both IRF-1 and p53 protein in nuclear
      extracts. Induction by TNF-alpha increased IRF-1 protein binding 3.5-fold, while
      binding levels of p53 protein increased six-fold. The addition of PYY to TNF
      treated cells reduced IRF-1 and p53 binding to control levels. CONCLUSIONS: We
      have shown for the first time that short-term exposure to TNF-alpha induces the
      binding activity of transcription factors IRF-1 and p53 in rat pancreatic acinar
      cells, and that addition of PYY reduces it. Regulation of transcription factor
      activity by PYY may have therapeutic potential in altering the progression of
      pancreatitis.

PMID- 16978651
TI  - Intraoperative colon mucosal oxygen saturation during aortic surgery.
AB  - BACKGROUND: Colonic ischemia after aortic reconstruction is a devastating
      complication with high mortality rates. This study evaluates whether Colon
      Mucosal Oxygen Saturation (CMOS) correlates with colon ischemia during aortic
      surgery. MATERIALS AND METHODS: Aortic reconstruction was performed in 25
      patients, using a spectrophotometer probe that was inserted in each patient's
      rectum before the surgical procedure. Continuous CMOS, buccal mucosal oxygen
      saturation, systemic mean arterial pressure, heart rate, pulse oximetry, and
      pivotal intra-operative events were collected. RESULTS: Endovascular aneurysm
      repair (EVAR) was performed in 20 and open repair in 5 patients with a mean age
      of 75 +/- 10 (+/-SE) years. CMOS reliably decreased in EVAR from a baseline of
      56% +/- 8% to 26 +/- 17% (P < 0.0001) during infrarenal aortic balloon occlusion
      and femoral arterial sheath placement. CMOS similarly decreased during open
      repair from 56% +/- 9% to 15 +/- 19% (P < 0.0001) when the infrarenal aorta and
      iliac arteries were clamped. When aortic circulation was restored in both EVAR
      and open surgery, CMOS returned to baseline values 56.5 +/- 10% (P = 0.81). Mean
      recovery time in CMOS after an aortic intervention was 6.4 +/- 3.3 min.
      Simultaneous buccal mucosal oxygen saturation was stable (82% +/- 6%) during
      aortic manipulation but would fall significantly during active bleeding. There
      were no device related CMOS measurement complications. CONCLUSIONS: Intra
      operative CMOS is a sensitive measure of colon ischemia where intraoperative
      events correlated well with changes in mucosal oxygen saturation. Transient
      changes demonstrate no problem. However, persistently low CMOS suggests colon
      ischemia, thus providing an opportunity to revascularize the inferior mesenteric
      artery or hypogastric arteries to prevent colon infarction.

PMID- 16978652
TI  - Endobronchial donor pre-treatment with ventavis: is a second administration
      during reperfusion beneficial to optimize post-ischemic function of non-heart
      beating donor lungs?
AB  - BACKGROUND: Lung retrieval from non-heart-beating donors (NHBD) has been
      introduced into clinical practice successfully. However, because of potentially
      deleterious effects of warm ischemia on microvascular integrity, use of NHBD
      lungs is limited by short tolerable time periods before preservation. Recently,
      improvement of NHBD graft function was demonstrated by donor pre-treatment using
      aerosolized Ventavis (Schering Inc., Berlin, Germany). Currently, there is no
      information whether additional application of this approach in reperfusion can
      further optimize immediate graft function. MATERIAL AND METHODS: Asystolic pigs
      (n = 5/group) were ventilated for 180-min of warm ischemia (groups 1-3). In
      groups 2 and 3, 100 microg Ventavis were aerosolized over 30-min using an
      ultrasonic nebulizer (Optineb). Lungs were then retrogradely preserved with
      Perfadex and stored for 3-h. After left lung transplantation and contralateral
      lung exclusion, grafts were reperfused for 6-h. Only in group 3, another dose of
      100 microg Ventavis was aerosolized during the first 30-min of reperfusion.
      Hemodynamics, pO2/FiO2 and dynamic compliance were monitored continuously and
      compared to controls. Intraalveolar edema was quantified stereologically, and
      extravascular-lung-water-index (EVLWI) was measured. Statistics comprised ANOVA
      analysis with repeated measurements. RESULTS: Dynamic compliance was
      significantly lower in both Ventavis groups, but additional administration did
      not result in further improvement. Oxygenation, pulmonary hemodynamics, EVLWI and
      intraalveolar edema formation were comparable between groups. CONCLUSIONS:
      Alveolar deposition of Ventavis in NHBD lungs before preservation significantly
      improves dynamic lung compliance and represents an important strategy for
      improvement of preservation quality and expansion of warm ischemic intervals.
      However, additional application of this method in early reperfusion is of no
      benefit.

PMID- 16978653
TI  - Shedding light on plant competition: modelling the influence of plant morphology
      on light capture (and vice versa).
AB  - A plant's morphology is both strongly influenced by local light availability and,
      simultaneously, strongly influences this local light availability. This
      reciprocal relationship is complex, but lies at the heart of understanding plant
      growth and competition. Here, we develop a sub-individual-based simulation model,
      cast at the level of interacting plant components. The model explicitly simulates
      growth, development and competition for light at the level of leaves, branches,
      etc., located in 3D space. In this way, we are able to explore the manner in
      which the low-level processes governing plant growth and development give rise to
      individual-, cohort-, and community-level phenomena. In particular, we show that
      individual-level trade-offs between growing up and growing out arise naturally in
      the model, and robustly give rise to cohort-level phenomena such as self
      thinning, and community processes such as the effect of ecological disturbance on
      the maintenance of biodiversity. We conclude with a note on our methodology and
      how to interpret the results of simulation models such as this one.

PMID- 16978654
TI  - Using reproductive value to estimate key parameters in density-independent age
      structured populations.
AB  - The dynamics of reproductive value are used to provide a simple derivation of
      Tuljapurkar's approximation for the long-run growth rate and environmental
      variance of lnN, in a density-independent age-structured population in a random
      environment. With no environmental autocorrelation, the dynamics of total
      population size, N, generally shows time lags and autocorrelation caused by life
      history, which may strongly bias estimates of environmental variance obtained by
      ignoring age structure. In contrast, the total reproductive value, V, is
      Markovian and obeys a first-order autoregressive process. This suggests a simple
      method for estimating the environmental variance, and avoiding potentially large
      bias due to age-structure fluctuations, by converting a multivariate time series
      of age structure to a univariate time series of lnV. We illustrate the method by
      estimating the long-run growth rate and the environmental variance in an
      exponentially growing population of Bighorn Sheep.

PMID- 16978655
TI  - Catechin and epicatechin from Smilacis chinae rhizome protect cultured rat
      cortical neurons against amyloid beta protein (25-35)-induced neurotoxicity
      through inhibition of cytosolic calcium elevation.
AB  - We previously reported that the Smilacis chinae rhizome inhibits amyloid beta
      protein (25-35) (Abeta (25-35))-induced neurotoxicity in cultured rat cortical
      neurons. Here, we isolated catechin and epicatechin from S. chinae rhizome and
      also studied their neuroprotective effects on Abeta (25-35)-induced neurotoxicity
      in cultured rat cortical neurons. Catechin and epicatechin inhibited 10 microM
      Abeta (25-35)-induced neuronal cell death at a concentration of 10 microM, which
      was measured by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide
      (MTT) assay and Hoechst 33342 staining. Catechin and epicatechin inhibited 10
      microM Abeta (25-35)-induced elevation of cytosolic calcium concentration
      ([Ca2+]c), which was measured by a fluorescent dye, Fluo-4 AM. Catechin and
      epicatechin also inhibited glutamate release into medium induced by 10 microM
      Abeta (25-35), which was measured by HPLC, generation of reactive oxygen species
      (ROS) and activation of caspase-3. These results suggest that catechin and
      epicatechin prevent Abeta (25-35)-induced neuronal cell damage by interfering
      with the increase of [Ca2+]c, and then by inhibiting glutamate release,
      generation of ROS and caspase-3 activity. Furthermore, these effects of catechin
      and epicatechin may be associated with the neuroprotective effect of the S.
      chinae rhizome.

PMID- 16978656
TI  - Evaluation of the role of the arachidonic acid cascade in anandamide's in vivo
      effects in mice.
AB  - The pharmacological profiles of the endocannabinoid anandamide and exogenous
      cannabinoids (e.g., Delta9-tetrahydrocannabinol) are similar, but not exactly the
      same. One notable difference is that anandamide's in vivo effects in mice are not
      blocked by the brain cannabinoid (CB1) receptor antagonist SR141716A. The degree
      to which the rapid metabolism of anandamide to arachidonic acid might be involved
      in this unexpected lack of effect was the focus of this study. Mice were tested
      in a tetrad of tests sensitive to cannabinoids, consisting of spontaneous
      locomotion, ring immobility, rectal temperature and tail flick nociception.
      Anandamide and arachidonic acid produced a similar profile of effects, but
      neither drug was blocked by SR141716A. When hydrolysis of anandamide was
      inhibited by an amidase inhibitor (phenylmethyl sulfonyl fluoride; PMSF),
      however, SR141716A significantly attenuated anandamide's effects but did not
      completely block them. Similarly, the effects of the metabolically stable
      anandamide analog O-1812 were attenuated by SR141716A. The role of oxidative
      metabolism in anandamide's effects in the tetrad was also investigated through
      pharmacological modulation of cyclooxygenase and lipoxygenase, two major classes
      of enzymes that degrade arachidonic acid. Whereas the non-selective
      cyclooxygenase inhibitor ibuprofen blocked the in vivo effects of arachidonic
      acid, it did not alter anandamide's effects. Other modulators of the
      cyclooxygenase and lipoxygenase pathways also failed to block anandamide's
      effects. Together, these results offer partial support for a pharmacokinetic
      explanation of the failure of SR141716A to antagonize the effects of anandamide;
      however, they also suggest that non-CB1, non-CB2 receptors may be involved in
      mediation of anandamide's in vivo actions, particularly at higher doses.

PMID- 16978657
TI  - Monitoring ligand-mediated internalization of G protein-coupled receptor as a
      novel pharmacological approach.
AB  - Agonist activation of a G protein-coupled receptor (GPCR) results in the
      redistribution of the receptor protein away from the cell surface into internal
      cellular compartments through a process of endocytosis known as internalization.
      Visualization of receptor internalization has become experimentally practicable
      by using fluorescent reagents such as green fluorescent protein (GFP). In this
      study, we examined whether the ligand-mediated internalization of a GPCR can be
      exploited for pharmacological evaluations. We acquired fluorescent images of
      cells expressing GFP-labeled GPCRs and evaluated the ligand-mediated
      internalization quantitatively by image processing. Using beta2-adrenoceptor and
      vasopressin V1a receptor as model GPCRs that couple to Gs and Gq, respectively,
      we first examined whether these GFP-tagged GPCRs exhibited appropriate
      pharmacology. The rank order of receptor internalization potency for a variety of
      agonists and antagonists specific to each receptor corresponded well with that
      previously observed in ligand binding studies. In addition to chemical ligand
      induced internalization, this cell-based fluorescence imaging system successfully
      monitored the internalization of the proton-sensing GPCR TDAG8, and that of the
      free fatty acid-sensitive GPCR GPR120. The results show that monitoring receptor
      internalization can be a useful approach for pharmacological characterization of
      GPCRs and in fishing for ligands of orphan GPCRs.

PMID- 16978659
TI  - Influence of the antipsychotic drug pipamperone on the expression of the dopamine
      D4 receptor.
AB  - The dopamine D4 receptor is a G protein-coupled receptor that binds with high
      affinity various antipsychotics. The receptor may be involved in
      attention/cognition, and in genetic studies a polymorphic repeat sequence in its
      coding sequence has been associated with attention deficit/hyperactivity
      disorder. We developed an inducible episomal expression system based on the
      reverse tetracycline transactivator and Epstein-Barr viral sequences. In
      HEK293rtTA cells expressing the dopamine D4 receptor from this episomal
      expression vector, addition of doxycycline in combination with sodium butyrate
      and trichostatin A induces high levels of receptor expression, resulting in 1970
      +/- 20 fmol/mg membrane protein. Addition of the dopamine D4 receptor and
      serotonin 5-HT2A receptor antagonist pipamperone to these cells further increased
      the expression of the dopamine receptor, reaching 3800 +/- 60 fmol/mg membrane
      protein. This up-regulation was not restricted to the dopamine D4 receptor but
      was also found for the serotonin 5-HT2A receptor. We further provide evidence
      that the increase in receptor expression is not due to increased mRNA synthesis.
      As pipamperone could rescue the expression of a folding mutant of the dopamine D4
      receptor (M345), we propose that pipamperone acts as a pharmacological chaperone
      for correct receptor folding thereby resulting in an increased dopamine D4
      receptor expression. This study describes a strong and inducible expression
      system for proteins, difficult to express in other heterologous expression
      systems. This study also demonstrates that pipamperone, an antipsychotic, acts as
      a pharmacological chaperone and by doing so, increases the expression level of
      the dopamine D4 receptor. The fact that ligands can also act as pharmacological
      chaperones is a fairly new additional element in the regulation of receptor
      expression levels with potential great impact in drug treatment.

PMID- 16978658
TI  - ERK1/2 and p38 mitogen-activated protein kinase mediate iNOS-induced spinal
      neuron degeneration after acute traumatic spinal cord injury.
AB  - The enhanced production of nitric oxide (NO) via inducible nitric oxide synthase
      (iNOS) has been implicated in the pathogenesis of neuronal apoptosis after acute
      traumatic spinal cord injury (SCI). In the present study, to further characterize
      the pathways mediating the synthesis and release of NO, we examined activation of
      extracellular signal regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated
      protein kinases (p38 MAPK) in microglia/macrophages in the injured area of adult
      rats subjected to a complete transection at the T10 vertebrae level and assessed
      their role in NO production and survival of neurons by using
      immunohistochemistry, Western blot, RT-PCR and pharmacological interventions.
      Results showed activation of microglia/macrophages featured by morphological
      changes, as visualized immunohistochemically with the marker OX-42, in the areas
      adjacent to the lesion epicenter 1 h after surgery. Concomitantly, iNOS mRNA and
      its protein in the activated microglia/macrophages were also significantly
      upregulated at early hours after surgery. Their levels were maximal at 6 h,
      persisted for at least 24 h, and returned to basal level 72 h after SCI.
      Furthermore, phosphorylated ERK1/2 and p38 MAPK were activated as well in
      microglia/macrophages in injured area with a similar time course as iNOS. With
      administration of L-NAME, a NOS inhibitor, the number of apoptotic neurons was
      clearly decreased, as assessed with TUNEL method at 24 h after SCI. In parallel,
      loss of neurons induced by SCI, assessed with NeuN immunohistochemistry, was also
      diminished. Moreover, the effect of inhibition of phosphorylation ERK1/2 and p38
      MAPK by corresponding inhibitors PD98059 and SB203580 administered before and
      after SCI was also investigated. Inhibition of p38 effectively reduced iNOS mRNA
      expression and rescued neurons from apoptosis and death in the area adjacent to
      the lesion epicenter; whereas the inhibition of ERK1/2 had a smaller effect on
      decrease of iNOS mRNA and no long-term protective effect on cell loss. These
      results indicate the ERK1/2 and p38 MAPK signaling pathway, especially the
      latter, play an important role in NO-mediated degeneration of neuron in the
      spinal cord following SCI. Strategies directed to blocking the initiation of this
      cascade prove to be beneficial for the treatment of acute SCI.

PMID- 16978660
TI  - Genomic-independent action of thyroid hormones on NTPDase activities in Sertoli
      cell cultures from congenital hypothyroid rats.
AB  - The Sertoli cells play an essential role in the maintenance and control of
      spermatogenesis. The ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase)
      and 5'-nucleotidase activities can modulate the extracellular adenine nucleotide
      levels, controlling nucleotide-mediated signaling events in Sertoli cells. Since
      thyroid hormones (TH) and adenine nucleotides and nucleosides play important
      modulatory roles in Sertoli cell proliferation and differentiation, the aim of
      our study was to investigate the effect of hypothyroidism upon the NTPDase and 5'
      nucleotidase activities in Sertoli cell cultures, as well as to verify whether
      these effects may be reversed by short and long-term supplementation with TH.
      Congenital hypothyroidism was induced by adding 0.02% methimazole in the drinking
      water from day 9 of gestation and continually until 18 days of age.
      Hypothyroidism significantly decreased the extracellular ATP and ADP hydrolysis
      and this effect was significantly reversed when cell cultures were supplemented
      with 1 microM T3 or 0.1 microM T4 for 30 min. In contrast, AMP hydrolysis was not
      altered by hypothyroidism, but was increased by T4 supplementation for 24 h. The
      presence of the enzymes NTPDase 1, 2 and 3 was detected by RT-PCR in Sertoli cell
      cultures, however, hypothyroidism was not able to alter the expression of these
      enzymes. These findings demonstrate that TH modify NTPDase activities in
      hypothyroid Sertoli cells, probably via nongenomic mechanisms and, consequently,
      may influence the reproductive function throughout development.

PMID- 16978661
TI  - The inhibitory effect of polyunsaturated fatty acids on human CYP enzymes.
AB  - The inhibitory effect of saturated fatty acids (SFAs): palmitic acid (PA),
      stearic acid (SA) and polyunsaturated fatty acids (PUFAs): linoleic acid (LA),
      linolenic acid (LN), arachidonic acid (AA), eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) on six human drug-metabolizing enzymes (CYP1A2, 2C9,
      2C19, 2D6, 2E1 and 3A4) was studied. Supersomes from baculovirus-expressing
      single isoforms were used as the enzyme source. Phenacetin O-deethylation
      (CYP1A2), diclofenac 4-hydroxylation (CYP2C9), mephenytoin 4-hydroxylation
      (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6
      hydroxylation (CYP2E1) and midazolam 1-hydroxylation (CYP3A4) were used as the
      probes. Results show that all the five examined PUFAs competitively inhibited
      CYP2C9- and CYP2C19-catalyzed metabolic reactions, with Ki values ranging from
      1.7 to 4.7 microM and 2.3 to 7.4 microM, respectively. Among these, AA, EPA and
      DHA tended to have greater inhibitory potencies (lower IC(50) and Ki values) than
      LA and LN. In addition, these five PUFAs also competitively inhibited the
      metabolic reactions catalyzed by CYP1A2, 2E1 and 3A4 to a lesser extent (Ki
      values>10 microM). On the other hand, palmitic and stearic acids, the saturated
      fatty acids, had no inhibitory effect on the activities of six human CYP isozymes
      at concentrations up to 200 microM. Incubation of PUFAs with CYP2C9 or CYP2C19 in
      the presence of NADPH resulted in the decrease of PUFA concentrations in the
      incubation mixtures. These results indicate that the PUFAs are potent inhibitors
      as well as the substrates of CYP2C9 and CYP2C19.

PMID- 16978662
TI  - Establishment of ex vivo systems to identify compounds acting on innate immune
      responses and to determine their target molecules using transgenic Drosophila.
AB  - Innate immunity is an evolutionarily conserved self-defense mechanism against
      microbial infections. In Drosophila, induction of antimicrobial peptides is a
      major immune response that is regulated by two distinct signaling pathways called
      the IMD pathway and the Toll pathway, similar to the tumor necrosis factor-alpha
      signaling and Toll-like receptor/interleukin-1 signaling pathways, respectively,
      in mammals. In mammals, innate immunity interacts with adaptive immunity and has
      a key role in the regulated immune response. Therefore, innate immunity is a
      pharmaceutical target for the development of immune regulators. Previously, based
      on the striking conservation between the mechanisms that regulate Drosophila
      immunity and human innate immunity, we established an ex vivo culture in which
      compounds acting on innate immunity can be evaluated using a reporter gene that
      reflects activation of the IMD pathway [Yajima et al. [Yajima, M., Takada, M.,
      Takahashi, N., Kikuchi, H., Natori, S., Oshima, Y., Kurata, S., 2003. A newly
      established in vitro culture using transgenic Drosophila reveals functional
      coupling between the phospholipase A2-generated fatty acid cascade and
      lipopolysaccharide-dependent activation of the immune deficiency (imd) pathway in
      insect immunity. The Biochemical Journal 371(Pt 1), 205-210] Biochem J 371, 205
      210]. Here, we combined the ex vivo culture with a reporter gene that reflects
      the heat shock response and demonstrated that the resulting systems are useful
      for screening compounds that act specifically on innate immunity, including
      mammalian innate immune responses. Identification of target molecules is
      essential for the development of more potent medicines with fewer side effects.
      In this study, we also established ex vivo systems capable of identifying target
      molecules of the identified compounds using targeted activation of the IMD
      pathway.

PMID- 16978663
TI  - Involvement of MAP kinases in lipopolysaccharide-induced histamine production in
      RAW 264 cells.
AB  - Roles of mitogen-activated protein (MAP) kinases in lipopolysaccharide (LPS)
      induced production of histamine in the mouse macrophage-like cell line RAW 264
      were analyzed. Incubation of RAW 264 cells in the presence of LPS increased
      histamine levels in the conditioned medium in a concentration- and time-dependent
      manner. The levels of histidine decarboxylase (HDC) mRNA and the 74-kDa HDC
      protein were also increased at 4 to 8 h and 8 to 12 h, respectively. LPS elicited
      the phosphorylation of p44/42 MAP kinase, p38 MAP kinase, and c-Jun N-terminal
      kinase (JNK). The MAP kinase-Erk kinase 1 inhibitor U0126 (0.1-10 microM)
      suppressed the LPS-induced phosphorylation of p44/42 MAP kinase, and inhibited
      the LPS-induced production of histamine and expression of the HDC mRNA and 74-kDa
      HDC protein in a concentration-dependent manner. The JNK inhibitor SP600125 (3-30
      microM) suppressed the LPS-induced phosphorylation of c-Jun, and inhibited the
      LPS-induced production of histamine and expression of the HDC mRNA and 74-kDa
      protein in a concentration-dependent manner. Combined treatment with U0126 (0.3
      microM) and SP600125 (10 microM) inhibited the LPS-induced production of
      histamine additively. The p38 MAP kinase inhibitor SB203580 (0.1-10 microM)
      partially inhibited the LPS-induced production of histamine. These findings
      suggest that LPS increases histamine production in RAW 264 cells by inducing the
      expression of the 74-kDa HDC protein, and that the LPS-induced expression of HDC
      is up-regulated at the transcriptional level by MAP kinases, especially p44 MAP
      kinase and JNK.

PMID- 16978664
TI  - Ultra high frequency-electromagnetic field irradiation during pregnancy leads to
      an increase in erythrocytes micronuclei incidence in rat offspring.
AB  - Mobile telephones and their base stations are an important ultra high frequency
      electromagnetic field (UHF-EMF) source and their utilization is increasing all
      over the world. Epidemiological studies suggested that low energy UHF-EMF emitted
      from a cellular telephone may cause biological effects, such as DNA damage and
      changes on oxidative metabolism. An in vivo mammalian cytogenetic test, the
      micronucleus (MN) assay, was used to investigate the occurrence of chromosomal
      damage in erythrocytes from rat offspring exposed to a non-thermal UHF-EMF from a
      cellular phone during their embryogenesis; the irradiated group showed a
      significant increase in MN occurrence. In order to investigate if UHF-EMF could
      also alter oxidative parameters in the peripheral blood and in the liver - an
      important hematopoietic tissue in rat embryos and newborns - we also measured the
      activity of antioxidant enzymes, quantified total sulfhydryl content, protein
      carbonyl groups, thiobarbituric acid-reactive species and total non-enzymatic
      antioxidant defense. No significant differences were found in any oxidative
      parameter of offspring blood and liver. The average number of pups in each litter
      has also not been significantly altered. Our results suggest that, under our
      experimental conditions, UHF-EMF is able to induce a genotoxic response in
      hematopoietic tissue during the embryogenesis through an unknown mechanism.

PMID- 16978665
TI  - Estimation of contrast agent concentration in intra- and extra-vascular spaces of
      brain tissue.
AB  - This article presents a new method for estimating the leakage of a contrast agent
      out of a vessel. The proposed method is developed based on tissue homogeneity
      (TH) model, modified Patlak model, and Monte Carlo simulation. The analytical
      methods published in the literature estimate the contrast agent leakage by
      solving the coupled differential equations associated with the TH model under
      adiabatic conditions. These methods employ unrealistic simplifying assumptions
      and become intractable in their applications to the vessels that have a non
      uniform permeability. Without making any unrealistic assumptions, our approach
      simply tracks the passage of the contrast agent through the capillary and its
      crossing of the vessel walls based on the blood flow in the vessel, the vessel's
      permeability, and the condition of the blood-brain barrier (BBB). These are
      treated as statistical processes that can be modeled reasonably well using the
      Monte Carlo method. In the proposed approach, the intra- and extra-vascular
      spaces are divided into multiple compartments, similar to the Patlak model. A
      real, measured arterial input function (AIF) is used as the capillary input and
      the concentration of the contrast agent is found as a function of time and
      distance, inside and outside of the capillary. This is done for normal and
      abnormal capillaries with uniform and non-uniform permeability. The proposed
      method generates concentration curves similar to those of the analytical method
      for simple AIF models. It also generates reasonable concentration curves for a
      real AIF. The proposed method does not fit a mathematical function to the
      measured AIF and does not make unrealistic simplifying assumptions. It is not
      therefore prone to the fitting errors and generates more realistic and more
      accurate results than the analytical methods.

PMID- 16978666
TI  - Characterizing rule-based category learning deficits in patients with Parkinson's
      disease.
AB  - Parkinson's disease (PD) patients and normal controls were tested in three
      category learning experiments to determine if previously observed rule-based
      category learning impairments in PD patients were due to deficits in selective
      attention or working memory. In Experiment 1, optimal categorization required
      participants to base their decision on a single stimulus dimension and ignore
      irrelevant variation on another dimension, thus emphasizing selective attention
      processes. In Experiment 2, optimal categorization required participants to base
      their decision on both stimulus dimensions using a conjunction of unidimensional
      decisions. Thus, this task placed less emphasis on selective attention and more
      on working memory. In Experiment 3, optimal categorization again required
      participants to base their decision on both stimulus dimensions using a
      disjunction of two unidimensional decisions in which an additional verbal
      operation was needed, thereby placing even greater emphasis on working memory.
      Results indicated that PD patients were impaired in the unidimensional rule-based
      condition, but not the other two rule-based conditions. These results are
      consistent with previous studies that demonstrate that PD patients are impaired
      in learning rule-based categories when selective attention demands are greatest,
      whereas these patients are normal in learning rule-based tasks when working
      memory demands are emphasized. Overall, these findings help to delineate the
      conditions under which PD patients display rule-based category learning deficits.

PMID- 16978668
TI  - Communicable disease control and contemporary themes in public health law.

PMID- 16978673
TI  - Amodiaquine combined with sulfadoxine/pyrimethamine versus artemisinin-based
      combinations for the treatment of uncomplicated falciparum malaria in Africa: a
      meta-analysis.
AB  - Drug resistance in Plasmodium falciparum is a major obstacle to malaria control.
      Artemisinin-based combination therapy (ACT) is being advocated to improve
      treatment efficacy and to delay development of resistance. Here we summarise the
      available data on the efficacy of amodiaquine plus sulfadoxine/pyrimethamine
      (AQ+SP) versus ACTs in the treatment of uncomplicated malaria in sub-Saharan
      Africa. We searched for randomised trials in which patients with uncomplicated
      malaria treated with AQ+SP were compared with those treated with either
      amodiaquine plus artesunate (AQ+AS), artesunate plus sulfadoxine/pyrimethamine
      (AS+SP) or artemether/lumefantrine (AL). Medline, EMBASE, Cochrane Central
      Register of Controlled Trials and reference lists up to July 2005 were searched.
      Two reviewers independently extracted the data. The primary outcome measure was
      treatment failure by Day 28. Outcome measures were combined using a random
      effects model. Seven randomised trials of 4472 children were included. Trial
      quality was generally high. Treatment failure of AQ+SP was significantly reduced
      compared with AS+SP (relative risk (RR)=0.56, 95% CI 0.42-0.75), but increased
      compared with AL (RR=2.80, 95% CI 2.32-3.39). The overall failure rate of AQ+SP
      was similar compared with AQ+AS (RR=1.12, 95% CI 0.81-1.54), but there was
      significant heterogeneity of results across the studies. All the treatment
      regimens were safe and well tolerated. AQ+SP should be considered in some
      settings before the full implementation of an ACT.

PMID- 16978674
TI  - Liquid chromatography-mass spectrometric assay of androstenediol in prostatic
      tissue: influence of androgen deprivation therapy on its level.
AB  - Androstenediol (Adiol, androst-5-ene-3beta,17beta-diol) is suspected of being an
      endogenous proliferation agent of prostate cancer (PCa) even after androgen
      deprivation therapy (ADT). A liquid chromatography-electron capture atmospheric
      pressure chemical ionization-mass spectrometric (LC-ECAPCI-MS) method for the
      determination of Adiol in prostatic tissue was developed and validated for
      evaluating the influence of ADT on the prostatic Adiol level. After
      derivatization of Adiol with 4-nitrobenzoyl chloride, the detection response of
      the derivative was increased 150 times more than that of intact Adiol. The LC-MS
      method was specific and reliable for the measurement of a trace amount of Adiol
      in 30 mg of tissue. The clinical study using the developed method showed that the
      prostatic Adiol level was not changed by ADT. That is, the prostatic Adiol levels
      of PCa patients with ADT (n = 12), benign prostate hypertrophy patients without
      ADT (n = 8) and bladder cancer patients (without prostatic disease) (n = 6) were
      0.83 +/- 0.28, 0.62 +/- 0.31 and 0.71 +/- 0.28 ng g(-1)tissue, respectively, and
      there was no significant difference between these groups.

PMID- 16978675
TI  - Advantage of storage in a fluctuating environment.
AB  - We will elaborate the evolutionary course of an ecosystem consisting of a
      population in a chemostat environment with periodically fluctuating nutrient
      supply. The organisms that make up the population consist of structural biomass
      and energy storage compartments. In a constant chemostat environment a species
      without energy storage always out-competes a species with energy reserves. This
      hinders evolution of species with storage from those without storage. Using the
      adaptive dynamics approach for non-equilibrium ecological systems we will show
      that in a fluctuating environment there are multiple stable evolutionary singular
      strategies (ss's): one for a species without, and one for a species with energy
      storage. The evolutionary end-point depends on the initial evolutionary state. We
      will formulate the invasion fitness in terms of Floquet multipliers for the
      oscillating non-autonomous system. Bifurcation theory is used to study points
      where due to evolutionary development by mutational steps, the long-term dynamics
      of the ecological system changes qualitatively. To that end, at the ecological
      time scale, the trait value at which invasion of a mutant into a resident
      population becomes possible can be calculated using numerical bifurcation
      analysis where the trait is used as the free parameter, because it is just a
      bifurcation point. In a constant environment there is a unique stable equilibrium
      for one species following the "competitive exclusion" principle. In contrast, due
      to the oscillatory dynamics on the ecological time scale two species may coexist.
      That is, non-equilibrium dynamics enhances biodiversity. However, we will show
      that this coexistence is not stable on the evolutionary time scale and always one
      single species survives.

PMID- 16978676
TI  - The epidermis of Timarete filigera (Polychaeta, Cirratulidae): histochemical and
      ultrastructural analysis of the gland cells.
AB  - The aim of this study was to verify whether different living conditions of
      Polychaeta are correlated with morphological and functional differences in the
      organization of the integument. For this purpose, we decided to study the
      epidermis of Timarete filigera, a non-tubicolous polychaete. With this objective
      in mind, we have identified the various cellular types responsible for mucous
      secretion in the epidermis of this species and defined the histochemical
      composition of the mucus produced by different types of gland cells. Three types
      of gland cells have been identified by histochemical and ultrastructural studies
      in the epidermis of this polychaete. The histochemistry was carried out using
      standard techniques and peroxidase-labelled lectins. In type 1 cells, the
      secretory granules contain neutral glycoproteins with glucosidic residues of
      GalNAc, Galbeta 1,3 GalNAc, glucosidic and/or mannosidic residues. In type 2
      cells, the secretory granules contain acid glycoproteins mainly sulphated with
      glucosidic residues of GalNAc, Galbeta 1,3 GalNAc, glucosidic and/or mannosidic
      residues, and some terminal sialic acid. In type 3 cells, the residual granules
      have the same chemical composition as that of granules present in type 2 cells.
      The secretion of these glandular mucous cells consists of mainly sulphated acidic
      glycoproteins and GAG resistant to testis jaluronidase. In these cells, the
      residual granules have the same chemical composition as that of their secretion.
      The heterogeneity of mucus composition may be correlated with its different
      functions.

PMID- 16978677
TI  - Is P-glycoprotein (ABCB1) a phase 0 or a phase 3 colchicine transporter depending
      on colchicine exposure conditions?
AB  - This study investigates the P-glycoprotein (Pgp)-mediated transport of its
      substrates in accumulation or efflux modes under steady-state conditions. The
      kinetics of colchicine uptake and efflux, a substrate of both Pgp and
      intracellular tubulin, were studied in HL60 and HL60/DNR cells; HL60/DNR cells
      contain 25 times more Pgp than do HL60 cells. HL60/DNR cells in a medium
      containing 6.25 nM colchicine, which mimics therapeutic conditions, reached
      steady-state twice as rapidly as did HL60 cells, and accumulated 24-times less
      colchicine than did HL60 cells. The Pgp inhibitor GF120918, increased colchicine
      uptake by HL60 cells 1.2-fold and that of HL60/DNR cells 17-fold, while it had no
      effect on colchicine efflux from either cell line that had been incubated with
      colchicine for 24 h. Colchicine kinetics fitted well a two closed-compartment
      model, showing that the low intracellular accumulation of colchicine in HL60/DNR
      cells resulted from a 11-fold decrease in colchicine uptake and a 2.3-fold
      increase in colchicine efflux, that could be attributed to Pgp-mediated efflux
      activity in HL60/DNR cells. Intracellular colchicine was mainly and similarly
      distributed in the cytosol in both cell lines. These data demonstrate that the
      kinetics of the intracellular colchicine accumulation depend on the density of
      Pgp and that Pgp is more a phase 0 (preventing cellular uptake) than a phase 3
      (effluxing intracellular substrate) transporter under steady-state conditions,
      although the situation is reversed after a short incubation time (30 min), when
      intracellular free colchicine concentration is probably high enough for it to be
      removed from the cell by Pgp.

PMID- 16978678
TI  - A proposed mechanism for amitriptyline neurotoxicity based on its detergent
      nature.
AB  - Although amitriptyline has gained attention as a potent local anesthetic, recent
      animal studies showed that it can cause irreversible neural impairment. We
      hypothesized that nerve membrane disruption caused by solubilization, a common
      detergent property, accounted for amitriptyline neurotoxicity. We used a two
      phase approach to test our hypothesis. Firstly, we determined (1) the molecular
      aggregation concentration of amitriptyline, (2) the concentration of
      amitriptyline that disrupts artificial lipid membranes and (3) the concentration
      of amitriptyline that causes hemolysis. Secondly, we compared these levels with
      neurotoxic concentrations determined from assessment in a rat model of spinal
      anesthesia using changes in cutaneous stimulus threshold (CST). Amitriptyline
      concentrations that caused molecular aggregation, model membrane disruption and
      hemolysis were 0.46%, 0.35% and 0.3%, respectively. Animal study showed a
      significant increase in CST at >or=0.3% of amitriptyline, indicating neurological
      impairment. Since amitriptyline caused model membrane disruption and hemolysis at
      the molecular aggregation concentration, solubilization plays a role in the
      destruction of artificial membranes and erythrocytes. Furthermore, these
      concentrations are also in good agreement with the minimum concentration causing
      neurological injury. Therefore, while additional studies, including
      histopathology, are necessary to clarify this observation, amitriptyline
      neurotoxicity appears to be associated with its detergent nature.

PMID- 16978679
TI  - Breakpoint chlorination and free-chlorine contact time: implications for drinking
      water N-nitrosodimethylamine concentrations.
AB  - North American drinking water utilities are increasingly incorporating
      alternative disinfectants, such as chloramines, in order to comply with
      disinfection by-product (DBP) regulations. N-Nitrosodimethylamine (NDMA) is a non
      halogenated DBP, associated with chloramination, having a drinking water unit
      risk two to three orders of magnitude greater than currently regulated
      halogenated DBPs. We quantified NDMA from two full-scale chloraminating water
      treatment plants in Alberta between 2003 and 2005 as well as conducted bench
      scale chloramination/breakpoint experiments to assess NDMA formation.
      Distribution system NDMA concentrations varied and tended to increase with
      increasing distribution residence time. Bench-scale disinfection experiments
      resulted in peak NDMA production near the theoretical monochloramine maximum in
      the sub-breakpoint region of the disinfection curve. Breakpoints for the raw and
      partially treated waters tested ranged from 1.9:1 to 2.4:1 (Cl(2):total NH(3)-N,
      M:M). Bench-scale experiments with free-chlorine contact (2h) before
      chloramination resulted in significant reductions in NDMA formation (up to 93%)
      compared to no free-chlorine contact time. Risk-tradeoff issues involving
      alternative disinfection methods and unregulated DBPs, such as NDMA, are emerging
      as a major water quality and public health information gap.

PMID- 16978680
TI  - Kinetics of struvite to newberyite transformation in the precipitation system
      MgCl2-NH4H2PO4NaOH-H2O.
AB  - The influence of the initial reactant concentrations on the composition of the
      solid phases formed in the precipitation system MgCl(2)-NH(4)H(2)PO(4)-NaOH-H(2)O
      was investigated. The precipitation diagram constructed shows the approximate
      concentration regions within which struvite, newberyite, and their mixtures exist
      at 25 degrees C and an aging time of 60 min. It was found that immediately after
      mixing the reactant solutions, struvite (MgNH(4)PO(4).6H(2)O) precipitated in
      nearly the whole concentration area, while newberyite (MgHPO(4).3H(2)O) appeared
      mostly within the region of the excess of magnesium concentration. It was also
      found that after aging time of 60 min the precipitation domain of struvite alone
      is much broader than that of newberyite or the domain of their coexistence, and
      shows that struvite is more abundant in the systems in which the initial
      concentration of ammonium phosphate is higher than that of magnesium. The
      kinetics of struvite to newberyite transformation (conversion) was systematically
      studied under the conditions of different initial reactant concentrations and
      different initial pH in the systems in which a mixture of both phases
      precipitated spontaneously. The struvite to newberyite conversion period was
      found to be strongly related to the ratio of initial supersaturations, S(N)/S(S),
      rather than to the any particular physical quantity that can describe and predict
      the behavior of the precipitation system. Experimental data suggest a solution
      mediated process as a most possible transformation mechanism. Along with a
      continuous monitoring of the changes in the liquid phase, the content of struvite
      in the solid phase was estimated by means of a Fourier transform infrared (FT-IR)
      method, developed for this particular precipitation system.

PMID- 16978681
TI  - Effect of photochemical treatment on the biocompatibility of a commercial
      nonionic surfactant used in the textile industry.
AB  - The degradability of surfactants is a frequent and complex issue arising both at
      domestic as well as industrial treatment facilities. The present paper describes
      a laboratory study conducted to elucidate the photochemical and biochemical
      treatability of a nonionic, alkyl polyethylene ether-based surfactant formulation
      commonly used in the textile preparation stage. The application of H(2)O(2)/UV-C
      advanced photochemical oxidation appeared to be a suitable treatment alternative
      and 90% COD removal (COD(0) approximately 500 mg/L) could be achieved under
      optimized process conditions. A significant COD removal efficiency (74%) could
      also be reached after biodegradation (final COD=135 mg/L) of the surfactant;
      however, necessitated an acclimation period of at least 6 weeks for the
      achievement of steady-state conditions. H(2)O(2)/UV-C treatment efficiency was
      seriously retarded upon elevation of the initial COD to around 1000 mg/L,
      resulting in 46% COD and 38% TOC removal after 120 min photochemical oxidation
      (H(2)O(2,0)=1020 mg/L; pH(0)=9.1). The BOD(5)/COD ratio increased from 0.23 to
      0.31 after the application of H(2)O(2)/UV-C revealing that photochemical
      pretreatment may have a positive effect on the ultimate biodegradation of the
      nonionic surfactant. Although the time required for activated sludge treatment to
      reach steady-state conditions could be reduced to 3 weeks for the photochemically
      pretreated surfactant formulation biochemical COD removal efficiency dramatically
      decreased from 74% to 39% for the nonionic surfactant being subjected to
      H(2)O(2)/UV-C pretreatment (ultimate COD after activated sludge treatment=265
      mg/L).

PMID- 16978682
TI  - Inverse estimation of nonpoint sources of fecal coliform for establishing
      allowable load for Wye River, Maryland.
AB  - An estimation of the nonpoint sources of fecal coliform (FC) has been formulated
      as an inverse parameter estimation problem, using FC observation data from the
      receiving waters. An inverse algorithm was integrated into the three-dimensional
      transport model, HEM-3D. The modified Gauss-Newton method was used for the
      optimal estimation of the loads. The approach is straightforward and requires
      less effort in modification of the existing hydrodynamic model. Model experiments
      were conducted to investigate the feasibility of load estimation in a tidal
      river. The parameter uncertainty and accuracy associated with load estimation are
      discussed using data sets with different sampling sizes. The inverse model was
      applied to the tidal Wye River, Maryland, USA, to estimate FC nonpoint sources
      and to develop an allowable load for the river to attain water quality standards.
      The model results suggest that the inverse modeling approach is suitable for
      estimating FC nonpoint sources. The inverse method not only provides an efficient
      approach to assess the contribution of nonpoint sources, but has the additional
      advantage of addressing the problems of the uncertainty and error associated with
      FC simulation in the estuary using hydrodynamic models.

PMID- 16978683
TI  - Accumulation of health disorders as a systemic measure of aging: Findings from
      the NLTCS data.
AB  - BACKGROUND: An index of age-associated health/well-being disorders (deficits),
      called the "frailty index" (FI), appears to be a promising characteristic to
      capture dynamic variability in aging manifestations among age-peers. In this
      study we provide further support toward this view focusing on the analysis of the
      FI age patterns in the participants of the National Long Term Care Survey
      (NLTCS). METHODS: The NLTCS assessed health and functioning of the U.S. elderly
      in 1982, 1984, 1989, 1994, and 1999. Detailed information for our sample was
      assessed from about 26,700 interviews. The individual FI is defined as a
      proportion of health deficits for a given person. RESULTS: The FI in the NLTCS
      exhibits accelerated age patterns. The acceleration is larger for elderly who, at
      younger ages, had a lower FI (low FI group) than for those who showed a higher FI
      at younger ages (high FI group). Age-patterns for low and high FI groups tend to
      converge at advanced ages. The rate of deficit accumulation is sex-sensitive.
      CONCLUSIONS: The accelerated FI age patterns suggest that FI can be considered as
      a systemic measure of aging process. Convergence of the (sex-specific) FI age
      patterns for low and high FI groups by extreme ages might reflect the limit of
      the FI-specific (or systemic) age as well as the limit of adaptation capacity in
      aging individuals.

PMID- 16978684
TI  - Composition of chlorinated hydrocarbon contaminants among major adipose tissue
      depots of polar bears (Ursus maritimus) from the Canadian high Arctic.
AB  - Monitoring of environmental contaminants in Canadian Arctic polar bears (Ursus
      maritimus) typically has used superficial adipose tissue samples collected as
      part of controlled native subsistence hunts. However, little attention has been
      paid to the compositional difference in contaminants that may exist among the
      major adipose depots that are routinely collected. To address this knowledge gap,
      we investigated the profiles and concentrations of chlorinated hydrocarbon
      contaminants (CHCs), including major polychlorinated biphenyl (PCB) congeners and
      organochlorine (OC) pesticides and metabolites, in six major adipose depots (i.e.
      superficial, inter-muscular and intra-abdominal regions) obtained from adult male
      polar bears in the vicinity of Resolute Bay, Canadian high Arctic. Concentrations
      and congener patterns of PCBs (20 congeners) and OCs (14 compounds; chlordanes
      and dichlorodiphenyltrichloroethanes and metabolites, chlorinated benzenes,
      hexachlorocyclohexane isomers, octachlorostyrene and dieldrin) were found to be
      relatively uniform throughout the adipose tissue of male polar bears. The only
      exception was the inter-muscular adipose depot from the cervical region, which
      was characterized, compared to other major depots routinely sampled, by lower
      proportions of higher-chlorinated and recalcitrant congeners such as CB170/190,
      180, 194 and 206, and higher contribution of the lower-chlorinated PCBs, CB47, 74
      and 99. No difference in the OC makeup and concentrations was found among the
      adipose depots investigated. In view of this, we conclude that the determination
      of CHCs in adipose tissue of polar bears from any major depots, with the
      potential exception of the fat under the neck muscles, would give a
      representative picture of the overall CHC composition and concentrations in polar
      bear fat for purpose of trend monitoring.

PMID- 16978685
TI  - Covalent antithrombin-heparin complexes.
AB  - Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have been
      utilized as primary anticoagulants for thrombosis prophylaxis and treatment.
      However, a number of biophysical and safety limitations have led to development
      of new anticoagulants. Covalent antithrombin-heparin (ATH) complexes may address
      many of these issues. Early ATH products were prepared that had increased
      intravenous half-lives relative to UFH but lacked any improvement in anti-factor
      Xa activity or had no catalytic activity or reactivity against thrombin. However,
      a recent conjugate developed by Chan et al. has displayed a number of superior
      properties. Chan et al. ATH has an increased direct thrombin inhibition rate and
      can catalyze coagulant enzyme inhibition by exogenous antithrombin with very high
      specific activity. Unlike UFH, clot-bound thrombin is readily inhibited by ATH
      and, at similar antithrombotic efficacy, the ATH has improved bleeding profiles
      compared to heparins. Given the preclinical findings, Chan et al. ATH may warrant
      clinical trial testing for control of clot propagation.

PMID- 16978686
TI  - Role for dopamine-3 receptor in the hyperphagia of an unanticipated high-fat meal
      in rats.
AB  - Behavioral studies have indicated that midbrain dopamine projections arising in
      the ventral tegmental area and substantia nigra play a central role in
      integrating violations of expectancy in reward-related paradigms. The present
      study was designed to assess violations of dietary expectation and the role the
      dopamine-3 receptor plays in integrating reward-related food intake in violations
      of expectancy. Two groups of rats were conditioned to a meal-feeding schedule (3
      h of access to food per day) in which they received either standard rodent chow
      or a preferable, high-fat diet. Animals either received the diet they had access
      to during the training period (no contrast) or the opposite diet (negative and
      positive contrast). As predicted, animals in the positive contrast condition were
      hyperphagic compared to no contrast animals. Animals in the negative contrast
      (high fat to chow) condition were hypophagic compared to no contrast animals. A
      dopamine agonist specific to the dopamine three receptor, ((+/-)-7-Hydroxy
      dipropylaminotetralin HBr) and the dopamine-2 receptor antagonist raclopride were
      administered in equimolar doses peripherally to assess the involvement of the
      dopamine receptor subtypes in the violation of expectancy food intake effects. 7
      Hydroxy-dipropylaminotetralin HBr blocked the hyperphagia associated with
      positive contrast and did not disrupt intake in the negative contrast or no
      contrast paradigm. Raclopride was ineffective at disrupting food intake. These
      results support the hypothesis that the dopamine-3 receptor is involved in the
      hyperphagia of an unexpected high fat meal.

PMID- 16978687
TI  - Predictors of US medical students' prevention counseling practices.
AB  - OBJECTIVE: To understand predictors of medical students' prevention counseling
      practices. METHODS: We surveyed medical students (n=2316 individuals) in the
      Class of 2003 at freshman orientation, and again at entrance to wards and senior
      year in a nationally representative sample of 16 US medical schools (response
      rate=80.3%). MAIN OUTCOME MEASURES: Perceived relevance of prevention counseling
      and seniors' frequency of prevention counseling. RESULTS: Healthier personal
      practices (p<0.0001), intention to become a primary care practitioner (p=0.0007),
      and attending a medical school that encouraged healthy personal practices
      (p=0.002) significantly predicted the frequency with which seniors reported
      currently counseling patients about preventive interventions (using a validated
      measure). Perceived counseling relevance was also significantly predicted by
      intention to become a primary care practitioner (p<0.0001), attending a school
      that encouraged healthy personal practices (p=0.0007), being earlier in one's
      training (p<0.0001), more interested in prevention (p<0.0001), female (p<0.0001),
      non-White (p=0.007), and by having healthy personal practices (p=0.008).
      CONCLUSIONS: Several of the variables predicting physician counseling also
      predict US medical students' reporting counseling (especially personal health
      practices and specialty type). In addition, the avidity with which medical
      schools encourage students to be healthy significantly influences their reported
      patient counseling. These findings can give a fresh, evidence-based direction to
      help create physicians who counsel patients about prevention.

PMID- 16978688
TI  - Autophagy as a cell-repair mechanism: activation of chaperone-mediated autophagy
      during oxidative stress.
AB  - Proper removal of oxidized proteins is an important determinant of success when
      evaluating the ability of cells to handle oxidative stress. The
      ubiquitin/proteasome system has been considered the main responsible mechanism
      for the removal of oxidized proteins, as it can discriminate between normal and
      altered proteins, and selectively target the latter ones for degradation. A
      possible role for lysosomes, the other major intracellular proteolytic system, in
      the removal of oxidized proteins has been often refused, mostly on the basis of
      the lack of selectivity of this system. Although most of the degradation of
      intracellular components in lysosomes (autophagy) takes place through "in bulk"
      sequestration of complete cytosolic regions, selective targeting of proteins to
      lysosomes for their degradation is also possible via what is known as chaperone
      mediated autophagy (CMA). In this work, we review recent evidence supporting the
      participation of CMA in the clearance of oxidized proteins in the forefront of
      the cellular response to oxidative stress. The consequences of an impairment in
      CMA activity, observed during aging and in some age-related disorders, are also
      discussed.

PMID- 16978689
TI  - Immunoglobulin G depletion from human serum with metal-chelated beads under
      magnetic field.
AB  - Magnetic poly(ethylene glycol dimethacrylate-N-methacryloyl-(L)-histidine methyl
      ester) [mag-poly(EGDMA-MAH) beads, 50-100 microm in diameter, were produced by
      suspension polymerization for affinity depletion of immunoglobulin G (IgG) from
      human serum. Cu2+ ions were complexed directly via MAH groups (Cu2+ loading: 4.1
      micromol/g). IgG depletion studies were performed by magnetically stabilized
      fluidized bed column. Acetate, Tris-HCl, MES and phosphate buffers all allow
      adsorption of similar quantities of IgG (27.3-45.6 mg/g). MOPS and HEPES allow
      higher adsorption quantities (79.6 mg/g and 74.1mg/g, respectively). Maximum
      adsorption capacities in MOPS buffer were 46.8 mg/g for mag-poly(EGDMA-MAH) and
      102.1mg/g for Cu2+ chelated mag-poly(EGDMA-MAH) beads. The adsorption capacity
      decreased drastically from 102.1mg/g to 30.7 mg/g with the increase of the flow
      rate from 0.2 ml/min to 3.5 ml/min. The elution studies were performed by 1.0M
      NaCl. The elution results demonstrated that the adsorption of IgG to the
      adsorbent was reversible. To test the efficiency of IgG depletion from human
      serum, proteins in the serum and eluted portion were analyzed by two-dimensional
      gel electrophoresis. The depletion efficiency for IgG was above 99.4%. Eluted
      proteins include mainly IgG, and a small number of non-albumin proteins such as
      apo-lipoprotein A1, sero-transferrin, haptoglobulin and alpha1-antitrypsin. When
      anti-HSA-sepharose adsorbent is used together with our metal-chelated mag-beads,
      IgG and HSA can be depleted in a single step.

PMID- 16978690
TI  - Orally administered marine (1-->3)-beta-D-glucan Phycarine stimulates both
      humoral and cellular immunity.
AB  - (1-->3)-beta-D-Glucans represent highly conserved structural components of cell
      walls in yeast, fungi, or seaweed. However, it is still unknown how they mediate
      their effects. The aim of this study was to evaluate both intraperitoneal and
      oral application of seaweed-derived (1-->3)-beta-D-glucan Phycarine. Phycarine
      showed significant stimulation of phagocytosis by peripheral blood cells. In
      addition, the efficiency of chemotherapy of Lewis lung carcinoma with
      cyclophosphamide was potentiated by Phycarine administration. Phycarine also
      strongly shortened the recovery of leucopenia caused either by chemotherapy or
      irradiation. Besides the role in stimulation of cellular immunity, we also found
      a significant increase of antibody formation. Using a suckling rat model for
      evaluation of the absorption and tissues distribution of enterally administered
      (125)I-Phycarine, we found that the majority of Phycarine was detected in the
      stomach and duodenum 5 min after the administration. This amount sharply
      decreased during first 30 min. A significant amount of Phycarine entered proximal
      intestine in a shortly after the gavage. Its transit through proximal intestine
      was decreasing with time and simultaneously increasing in the ileum. Systemic
      blood levels were very low (less than 0.5%). Taken together, these observations
      suggest that Phycarine is similarly effective both after i.p. and oral
      application, has very strong stimulating effects on three types of experimentally
      induced leucopenia and stimulates both humoral and cellular branch of immune
      reactions. The majority of Phycarine can be detected throughout the
      gastrointestinal tract, supporting the feasibility of enteral administration of
      Phycarine in the treatment of gastrointestinal diseases.

PMID- 16978691
TI  - The interrelated role of fibronectin and interleukin-1 in biomaterial-modulated
      macrophage function.
AB  - Macrophages play a critical role in mediating the host response to biomaterials,
      perhaps most notably by guiding the host inflammatory response through the
      release of inflammatory molecules such as the cytokine interleukin-1 (IL-1). The
      extent of the macrophage response following interaction with the biomaterial
      surface contributes greatly to device efficacy, yet the molecular mechanisms of
      this interaction are still unclear. The extracellular matrix (ECM) protein
      fibronectin (FN) is recognized by macrophages and frequently used in biomaterial
      modification to elicit greater cellular adhesion and tissue integration.
      Macrophage interaction with FN and other ECM molecules on the biomaterial surface
      has been shown to induce a variety of inflammatory responses, thus both FN and IL
      1 can be utilized as model molecules to better understand the mechanisms of
      material-mediated macrophage responses. This literature review presents a
      comprehensive survey of past and current research on the interrelated role of IL
      1, FN, and FN-derivatives in determining biomaterial-modulated macrophage
      function.

PMID- 16978692
TI  - Polylysine-functionalised thermoresponsive chitosan hydrogel for neural tissue
      engineering.
AB  - Foetal mouse cortical cells were cultured on 2D films and within 3D thermally
      responsive chitosan/glycerophosphate salt (GP) hydrogels. The biocompatibility of
      chitosan/GP 2D films was assessed in terms of cell number and neurites per cell.
      Osmolarity of the hydrogel was a critical factor in promoting cell survival with
      isotonic GP concentrations providing optimal conditions. To improve cell adhesion
      and neurite outgrowth, poly-D-lysine (PDL) was immobilised onto chitosan via
      azidoaniline photocoupling. Increase in PDL concentrations did not alter cell
      survival in 2D cultures but neurite outgrowth was significantly inhibited.
      Neurons exhibited a star-like morphology typical of 2D culture systems. The
      effects of PDL attachment on cell number, cell morphology and neurite outgrowth
      were more distinct in 3D culture conditions. Neurones exhibited larger cell
      bodies and sent out single neurites within the macroporous gel. Immobilised PDL
      improved cell survival up to an optimum concentration of 0.1%, however, further
      increases resulted in drops in cell number and neurite outgrowth. This was
      attributed to a higher cell interaction with PDL within a 3D hydrogel compared to
      the corresponding 2D surface. The results show that thermally responsive
      chitosan/GP hydrogels provide a suitable 3D scaffolding environment for neural
      tissue engineering.

PMID- 16978693
TI  - The MR tracking of transplanted ATDC5 cells using fluorinated poly-L-lysine-CF3.
AB  - Magnetic resonance (MR) imaging using super-paramagnetic iron oxides (SPIOs) is a
      powerful tool to monitor transplanted cells in living animals. However, since
      SPIOs are negative contrast agents it is difficult to track transplanted cells in
      bone and cartilage that originally display low signals. In this study, we
      examined the feasibility of tracking with fluorescein isothiocyanate (FITC)
      labeled poly-L-lysine-CF(3) (PLK-CF(3)) using mouse ATDC5 cells, a stem cell line
      of bone and cartilage cells. FITC-labeled PLK-CF(3) was easily internalized by
      ATDC5 cells by adding it into culture medium. No acute or long-term toxicities
      were seen at less than 160 microg/ml. Labeled cells transplanted into the cranial
      bone of mice were detected for at least 7 days by MR images. FITC-labeled PLK
      CF(3) is a useful positive contrast agent for MR tracking in bone and cartilage.

PMID- 16978694
TI  - Low-dose thalidomide in combination with oral fludarabine and cyclophosphamide is
      ineffective in heavily pretreated patients with chronic lymphocytic leukemia.

PMID- 16978695
TI  - Acute promyelocytic leukemia-mobile and infiltrative.

PMID- 16978696
TI  - Imatinib-induced apoptosis in the eosinophils of patients with a
      hypereosinophilic syndrome: a surrogate marker of response?

PMID- 16978698
TI  - Respiratory syncytial virus inhibits interferon-alpha-inducible signaling in
      macrophage-like U937 cells.
AB  - Monocytes become susceptible to respiratory syncytial virus (RSV) infection when
      pretreated with phorbol 12-myristate 13-acetate (PMA). The molecular mechanism
      underlying this observation is poorly understood, but may be related to
      inhibition of type I interferon (IFN) signaling by RSV in epithelial cells.
      Herein, we have investigated the putative role of suppressor of cytokine
      signaling (SOCS) in the IFN-inducible antiviral response in U937 cells. Upon RSV
      infection of macrophage-like U937 cells, the expression of SOCS1, SOCS3, and CIS
      mRNA was rapidly upregulated, and phosphorylation of the IFN-alpha-inducible
      signal transducer and activator of transcription (STAT1 and STAT2) was
      suppressed. These results suggest that RSV can inhibit the phosphorylation of IFN
      alpha-inducible STAT1 and STAT2 by inducing the expression of SOCS proteins in
      PMA-treated U937 cells.

PMID- 16978697
TI  - Brain magnetic resonance imaging and manganese concentrations in red blood cells
      of smelting workers: search for biomarkers of manganese exposure.
AB  - The MRI technique has been used in diagnosis of manganism in humans and non-human
      primates. This cross-sectional study was designed to explore whether the pallidal
      signal intensity in T1-weighted MRI correlated with Mn levels in the blood
      compartment among Mn-exposed workers and to understand to what extent the MRI
      signal could reflect Mn exposure. A group of 18 randomly selected male Mn-exposed
      workers of which 13 were smelting workers with high exposure (mean of airborne Mn
      in work place: 1.26 mg/m3; range: 0.31-2.93 mg/m3), and 5 power distribution
      control workers with low exposure (0.66 mg/m3 and 0.23-0.77 mg/m3) from a
      ferroalloy factory, and another group of 9 male subjects as controls from a non
      smelting factory who were office or cafeteria workers (0.01 mg/m3 and 0-0.03
      mg/m3) were recruited for neurological tests, MRI examination, and analysis of Mn
      in whole blood (MnB), plasma (MnP) or red blood cells (MnRBC). No clinical
      symptoms and signs of manganism were observed among these workers. MRI data
      showed average increases of 7.4% (p<0.05) and 16.1% (p<0.01) in pallidal index
      (PI) among low- and high-exposed workers, respectively, as compared to controls.
      Fourteen out of 18 Mn-exposed workers (78%) had intensified PI values, while this
      proportion was even higher (85%) among the high Mn-exposed workers. Among exposed
      workers, the PI values were significantly associated with MnRBC (r=0.55, p=0.02).
      Our data suggest that the workers exposed to airborne Mn, but without clinical
      symptoms, display an exposure-related, intensified MRI signal. The MRI, as well
      as MnRBC, may be useful in early diagnosis of Mn exposure.

PMID- 16978699
TI  - Antibiotic-lock therapy in central venous catheter colonization in patients with
      intestinal failure.

PMID- 16978700
TI  - Enantioseparation of tetrahydropalmatine and Troger's base by molecularly
      imprinted monolith in capillary electrochromatography.
AB  - Two chiral compounds, Troger's base and tetrahydropalmatine, were
      enantioseparated on the (5S, 11S)-(-)-Troger's base and l-tetrahydropalmatine
      imprinted monolithic capillary columns with CEC, respectively. The monoliths were
      prepared by in situ thermal-initiated copolymerization of methacrylic acid (MAA)
      and ethylene dimethacrylate (EDMA). After optimizing the ratio of porogens
      (toluene and dodecanol), the obtained monolithic capillary columns show good flow
      through property and enantioselectivity. The influences of CEC parameters such as
      pH of the buffer, organic solvent and salt concentration on the electroosmotic
      flow (EOF) and recognition selectivity were systematically investigated. Under
      the optimal conditions, baseline resolutions of two chiral compounds were
      achieved. In addition, the fast separation was obtained within 4 min by applying
      higher voltage and assisting pressure of 6 bar.

PMID- 16978701
TI  - Enantioseparation by ligand-exchange using particle-loaded monoliths: capillary
      LC versus capillary electrochromatography.
AB  - Particle-loaded monoliths containing a polymethacrylamide backbone were prepared
      by suspending a silica-based chiral phase in the mixture of the monomers followed
      by in-situ polymerization in the capillary. As chiral selector l-4-hydroxyproline
      chemically bonded to 3 microm silica particles was used following the separation
      principle of ligand-exchange. Electrolytes containing Cu(II) ions were used.
      Amino acid enantiomers were separated by capillary-LC and CEC, whereby the latter
      showed the better resolution properties. For the chiral separation of alpha
      hydroxy acids the EOF was reversed by copolymerizing diallyldimethylammonium
      chloride instead of vinylsulfonic acid as charge providing agent. Short columns
      of 6 cm were found to be sufficient in the case of CEC for baseline separations
      of amino acids with alpha values up to 5.

PMID- 16978702
TI  - On-line psychophysical data acquisition and event-related fMRI protocol optimized
      for the investigation of brain activation in response to gustatory stimuli.
AB  - An experimental method for event-related functional magnetic resonance imaging
      that allows for the presentation of several chemosensory stimuli in the oral
      cavity during the same run, the collection of psychophysical measures (intensity
      or pleasantness) during the presentation of the stimuli, and the analysis of the
      data in an event-related fashion are described. The automatic pumps used to
      present taste stimuli allowed for multiple tastes to be delivered in small
      amounts under computer control. Psychophysical ratings of pleasantness or
      intensity were collected after each presentation of a taste stimulus and water,
      with the general labeled magnitude scale, using a joystick that controlled the
      movement of an arrow on the visual display. Performing these cognitive tasks
      required that the participant remained focused, and aided in the interpretation
      of the data collected. The perceived pleasantness differed across stimuli for all
      conditions; however, pleasantness ratings for the same stimulus displayed
      consistency, over the duration of the run and before each scan on separate days.
      Activation in response to sucrose and caffeine while the participant rated
      pleasantness was found in the insula, frontal operculum, rolandic operculum and
      orbitofrontal cortex which is consistent with previous taste fMRI studies.

PMID- 16978704
TI  - Chemically induced model of hypermethioninemia in rats.
AB  - In the present study, we developed a chronic chemically induced model of
      hypermethioninemia in rats. We induced elevated concentrations of methionine in
      the blood by injecting subcutaneously methionine (1.34-2.68 micromol/g of body
      weight) to developing animals of various ages. Brain methionine concentrations
      were approximately 1.25 micromol/g wet tissue ( approximately 1.0mM). We then
      injected the same doses of methionine to young rats twice a day at 8h intervals
      from the 6(th) to the 28(th) postpartum day. Controls received saline in the same
      volumes. The body, brain and hippocampus of rats were weighed after treatment and
      showed that hypermethioninemic animals had no differences in these parameters,
      when compared to the control group, suggesting that methionine did not cause
      malnutrition in the rats. Considering that experimental animal models are useful
      to understand the pathophysiology of human disease, the present model of
      hypermethioninemia may contribute to the investigation of the mechanisms of brain
      damage caused by high tissue methionine levels.

PMID- 16978703
TI  - Monitoring extracellular glutamate in hippocampal slices with a microsensor.
AB  - The direct local assessment of glutamate in brain slices may improve our
      understanding of glutamatergic neurotransmission significantly. However, an
      analytical technique that monitors glutamate directly in brain slices is
      currently not available. Most recording techniques either monitor derivatives of
      glutamate or detect glutamate that diffuses out of the slice. Microsensors
      provide a promising solution to fulfill this analytical requirement. In the
      present study we have implanted a 10 microm diameter hydrogel-coated microsensor
      in the CA1 area of hippocampal slices to monitor extracellular glutamate levels.
      The influence of several pharmacological agents, which facilitate glutamate
      release from neurons or astrocytes, was investigated to explore the applicability
      of the microsensor. It was observed that KCl, veratradine, alpha-latrotoxine
      (LTX), DL-threo-beta-benzyloxyaspartate (dl-TBOA) and L-cystine rapidly increased
      the extracellular glutamate levels. As far as we know this is the first study in
      which a microsensor is applied to monitor dynamic changes of glutamate in brain
      slices and in our opinion this type of research may contribute greatly to improve
      our understanding of the physiology of glutamatergic neurotransmission.

PMID- 16978705
TI  - Endoscopic eye tracking system for fMRI.
AB  - Here we introduce a new video-based real-time eye tracking system suitable for
      functional magnetic resonance imaging (fMRI) application. The described system
      monitors the subject's eye, which is illuminated with infrared light, directly at
      the headcoil using an endoscopic fibre optical system. This endoscopic technique
      assures reliable, easy-to-use and fast adjustment. It requires only a minimal
      amount of equipment at the headcoil and inside the examination room. Moreover,
      the short distance between the image acquisition optics and the eye provides high
      spatial tracking resolution. Interference from physiological head movement is
      effectively reduced by simultaneous tracking of both eye and head movements.

PMID- 16978707
TI  - Variations in time of hospital presentation for deliberate self-harm and their
      implications for clinical services.
AB  - BACKGROUND: Variation in number, characteristics and management of deliberate
      self-harm (DSH) patients presenting to hospital during the 24-h cycle and day of
      the week may have implications for patient services. We have investigated how
      patient characteristics and clinical management of DSH episodes vary according to
      hour and day of presentation. METHODS: Time of presentation was studied in 5348
      DSH patients who presented to a general hospital following 9101 episodes during a
      6-year period. Patient characteristics were identified through routine clinical
      monitoring. RESULTS: Presentations varied markedly during the 24-h cycle, ranging
      from a peak between 8 pm and 3 am (average hourly rate of 6.6% of all episodes)
      to a low between 4 am and 10 am (1.4%). The majority (72.0%) occurred outside
      office hours. DSH associated with alcohol use and interpersonal problems was more
      frequent during the late evening or night, and at the weekend. A greater
      proportion of daytime presentations involved high suicide intent (although a
      larger number of high intent acts presented at other times), and more were
      admitted and assessed. LIMITATIONS: This study was based on DSH presentations to
      one hospital. Time and date of presentation and of psychosocial assessment, not
      time of DSH, were available for analysis. CONCLUSIONS: Peak times for DSH
      presentations are at night and the weekend, suggesting that specialist DSH
      services in general hospitals should be available 24 h a day, 7 days a week. Time
      of presentation should not be used as a proxy measure of suicide intent.

PMID- 16978706
TI  - Comorbid substance and mental disorders among rural Americans: results from the
      National Comorbidity Survey.
AB  - BACKGROUND: The purpose of this study was to examine whether rural inhabitants
      were more likely than urban inhabitants to meet the criteria for comorbid mental
      health and substance abuse or dependence disorders. METHODS: Data were from the
      National Comorbidity Survey, and included 5185 (532=rural; 4653=urban) persons
      age 14-54 years of age who were interviewed using the Composite International
      Diagnostic Interview (CIDI). Logistic regression that accounted for the complex
      survey data and weighting scheme was utilized. RESULTS: Participants residing in
      rural areas were more likely to meet the DSM-III-R criteria for past month
      alcohol abuse or dependence if they also met the diagnostic criteria for past
      month major depressive disorder (MDD) or lifetime antisocial personality disorder
      (ASPD), adjusting for age, race, gender, education and income. Similarly, rural
      participants were more likely to meet the criteria for comorbid drug abuse or
      dependence in the past month if they met the diagnosis for either past month MDD,
      generalized anxiety disorder or lifetime ASPD, controlling for demographic
      characteristics. Rural residents with any current mental disorder also were less
      likely to seek treatment than their urban counterparts. LIMITATIONS: Data were
      collected in 1991 and do not capture changes in prevalence of comorbidities.
      Also, the small number of rural residents sampled resulted in small cell sizes
      for some comorbidities. CONCLUSIONS: Rural residents were significantly more
      likely to meet the criteria for substance disorders given they also met the
      criteria for a mental disorder, and those with any current mental disorder were
      less likely to seek treatment. Since the overall prevalence of these disorders
      does not differ between rural and urban inhabitants, findings suggest that rural
      persons may lack access to adequate treatment for their mental health disorders
      and subsequently may be self-medicating with alcohol and/or drugs.

PMID- 16978708
TI  - Gene expression responses to a Salmonella infection in the chicken intestine
      differ between lines.
AB  - Poultry products are an important source of Salmonella enterica. An effective way
      to reduce food poisoning due to Salmonella would be to breed chickens more
      resistant to Salmonella. Unfortunately host responses to Salmonella are complex
      with many factors involved. To learn more about responses to Salmonella in young
      chickens, a cDNA microarray analysis was performed to compare gene expression
      profiles between two chicken lines under control and Salmonella infected
      conditions. Newly hatched chickens were orally infected with S. enterica serovar
      Enteritidis. Since the intestine is the first barrier the bacteria encounter
      after oral inoculation, intestinal gene expression was investigated at different
      timepoints. Differences in gene expression between the two chicken lines were
      found in control as well as Salmonella infected conditions. In response to the
      Salmonella infection a fast growing chicken broiler line induced genes that
      affect T-cell activation, whereas in a slow growing broiler line genes involved
      in macrophage activation seemed to be more affected at day 1 post-infection. At
      days 7 and 9 most gene expression differences between the two chicken lines were
      identified under control conditions, indicating a difference in the intestinal
      development between the two chicken lines which might be linked to the difference
      in Salmonella susceptibility. The findings in this study have lead to the
      identification of novel genes and possible cellular pathways, which are host
      dependent.

PMID- 16978709
TI  - Characterization of conventional and plasmacytoid dendritic cells in swine
      secondary lymphoid organs and blood.
AB  - Dendritic cells (DCs) act as antigen presenting cells that bridge innate and
      adaptive immune systems with the unique capacity to initiate primary T-cell
      responses and efficiently stimulate memory responses. In pig, little information
      is available about these cells in secondary lymphoid organs, the place where T
      cell activation usually occurs. As increased knowledge on DC is a necessary
      prerequisite to further understand their role in response to microbial infection
      or in protection after vaccination, we investigated the DC types that would be
      present in tonsil, spleen and non-subcutaneous lymph nodes in the steady state.
      One population was composed of CD172a(+)CD11R1(+)CD1(+/-)CD80/86(+/-) cells and
      would correspond to conventional DCs (cDC), while the other one was composed of
      CD172a(+)CD4(+)CD1(+/-)CD80/86(+/-) cells and would correspond to plasmacytoid
      DCs (pDC). These subsets were also detected in blood but spleen was the tissue
      with the higher frequency of such DCs. In lymphoid organs, most of cDC and pDC
      were in an immature status, as revealed by the low percentage of cells expressing
      the co-stimulatory molecule CD80/86. However, expression of that marker by 5% of
      DCs in organs and up to 15% in blood, together with lower expression of CD1a and
      expression of CD208, would indicate a partial activation and/or semi-maturation.
      Interestingly, 8% of tonsil pDC and 15% of blood pDC were shown to secrete IFN
      alpha, while 18-20% of cDC expressed TNF-alpha in these tissues. Both cell types
      also expressed IL-12 and IL-10 in the steady state. Measurements of IFN-alpha,
      TNF-alpha, IL-12 and IL-10 levels in serum confirmed their production within
      immune homeostasis, whereas IL-6, IL-18 and IFN-gamma could not be detected.
      Altogether, these data complete knowledge on porcine immune system cells and will
      be a useful tool for further in vivo studies on porcine DC role in peripheral
      tolerance induction and in immune responses to pathogens.

PMID- 16978710
TI  - Primary cricopharyngeal achalasia in a newborn treated by balloon dilatation: a
      case report and review of the literature.
AB  - Primary crycopharyngeal achalasia consists of a failure of the crycopharyngeus
      muscle to relax at the appropriate time during the swallowing process in the
      abscence of other motor abnormalities. The principle treatment options for
      cricopharyngeal achalasia include either dilatation of the upper esophagus or
      surgical myotomy of the cricopharyngeus muscle. We report a primary
      cricopharyngeal achalasia case, who was diagnosed early in 1st week of life and
      treated successfully by balloon dilatation, and discuss the treatment options for
      this very rare disease. The presented case is the first successfully treated
      newborn case during the neonatal period in the literature with respect to balloon
      dilatation.

PMID- 16978711
TI  - 3D-FLAIR magnetic resonance imaging in the evaluation of mumps deafness.
AB  - A 6-year-old boy suffered acute profound right side deafness after his classmates
      had mumps. Although his salivary glands were not swollen, he had high levels of
      anti-mumps IgM and IgG antibodies. The three-dimensional fluid-attenuated
      inversion recovery (3D-FLAIR) procedure applied to magnetic resonance imaging
      (MRI) showed high signals in the right cochlea and vestibule. This indicated
      hemorrhage or a high concentration of protein in the right inner ear. This is the
      first case demonstrating a high 3D-FLAIR MRI signal of the inner ear in a patient
      with mumps deafness. Our findings suggest that 3D-FLAIR MRI may help to identify
      and define labyrinthitis in mumps deafness.

PMID- 16978712
TI  - Evaluation of FTA paper and phenol for storage, extraction and molecular
      characterization of infectious bursal disease virus.
AB  - Infectious bursal disease virus (IBDV) is an important poultry pathogen and is
      distributed world wide that can cause immune suppression and lesions of the bursa
      of Fabricius. The main component of the virus, VP2, is not only responsible for
      the bird's immune response, but is important for the molecular identification of
      this virus as well. The nucleic acid of the virus must be adequately preserved to
      be analyzed by reverse-transcriptase PCR (RT-PCR) and sequenced for the molecular
      characterization of the field strain. Phenol inactivation has been the standard
      for IBDV tissue collection and international shipment; however, there have been
      some reports of interference with molecular detection capabilities when using
      phenol. Phenol is also a hazardous chemical and must be handled and shipped
      carefully. The ability to use the Flinders Technology Associates filter paper
      (FTA card) for inactivation of several avian pathogens has been proven
      previously, however no work has been published on its use in IBDV nucleic acid
      detection. Bursas from experimentally infected birds was imprinted on FTA cards,
      and then placed in phenol. Samples were evaluated and compared based on molecular
      detection capabilities between the two inactivation methods. The nucleic acid of
      the virus was detected in 85% of the FTA card inactivated samples compared to 71%
      in the phenol inactivated samples. Sequence analysis was performed on samples
      inactivated by both methods and no differences were found. When comparing the RNA
      stability at different temperatures, euthanized IBDV infected birds were held at
      two different temperatures before sampling. No differences were detected for FTA
      sampling; however, for tissues in phenol the nucleic acid was only detectable up
      to 2 h post-mortem in the tissues held at 4 degrees C prior to sampling. These
      findings indicate that the FTA card is an efficient and reliable alternative
      collection method for molecular detection and characterization of IBDV.

PMID- 16978713
TI  - Recombinant haemagglutinin neuraminidase antigen-based single serum dilution
      ELISA for rapid serological profiling of Newcastle disease virus.
AB  - A recombinant haemagglutinin neuraminidase (HN) antigen-based single serum
      dilution enzyme linked immuno-sorbent assay (ELISA) was developed to measure the
      specific antibody in sera of chickens against Newcastle disease virus. A linear
      relationship was found between the predicted antibody titres at a single working
      dilution of 1:1000 and the corresponding observed serum titres as determined by
      the standard serial dilution method. Regression analysis was used to determine a
      standard curve from which an equation was derived that allowed the demonstration
      of this correlation. The equation was then used to convert the corrected
      absorbance readings of the single working dilution directly into the predicted
      ELISA antibody titres. The assay proved to be sensitive, specific and accurate as
      compared to the standard haemagglutination inhibition (HI) test.

PMID- 16978714
TI  - Systemic administration of a dopamine, but not a serotonin or norepinephrine,
      transporter inhibitor reinstates cocaine seeking in the rat.
AB  - Reinstatement of cocaine-seeking behavior can be elicited by a systemic priming
      injection of cocaine or a non-selective biogenic amine transporter inhibitor. In
      order to determine which biogenic amine is responsible for this effect, selective
      dopamine (GBR 12909), serotonin (fluoxetine) or norepinephrine (nisoxetine)
      transporter inhibitors were systemically administered in order to assess their
      ability to induce cocaine seeking in rats. Administration of GBR 12909, but not
      nisoxetine or fluoxetine, dose-dependently reinstated cocaine seeking in rats.
      Furthermore, administration of the non-selective dopamine receptor antagonist
      flupenthixol into the nucleus accumbens shell attenuated GBR 12909-induced
      reinstatement of cocaine seeking. These results suggest that increases in
      extracellular concentrations of dopamine, specifically in the nucleus accumbens
      shell, are primarily responsible for promoting cocaine priming-induced
      reinstatement of drug seeking in rats.

PMID- 16978715
TI  - Effects of raclopride on aggression and stress in diversely selected chicken
      lines.
AB  - Genetic selection for chickens of high (HGPS) and low (LGPS) group productivity
      and survivability, resulted in two distinct genetic lines characterized by
      differences in cannibalism, flightiness, and immunocompetence. Additionally,
      birds exhibited differences in behaviour and social stress coping strategy. HGPS
      birds have a superior stress coping strategy compared with birds of LGPS or
      Dekalb XL (DXL), a commercial strain. Line differences in stress response and
      behaviour could be due to selection-induced differences in expression of the
      dopaminergic system. The dopamine (D2) receptor, an integral part of the
      dopaminergic system, was hypothesized to be a key contributory factor of the
      stress response. We tested this hypothesis by injecting either a D2 antagonist
      (raclopride) or saline in the dominant individual in pair-housed birds for 10
      days and examining stress coping ability. Results showed that dominant birds of
      all strains showed a reduced frequency of aggressive pecks on subordinates
      following raclopride injection. In contrast, subordinates paired with raclopride
      injected birds increased pecking frequency. Two days after stopping injections,
      LGPS and DXL birds returned to pre-injection levels of aggressive threats, while
      HGPS birds maintained depressed frequency of threats. Strain differences in
      aggressive responsiveness coincided with increased epinephrine levels in
      raclopride treated LGPS birds relative to control LGPS birds, but not by HGPS and
      DXL birds. Our findings suggest a functional linkage between the genetic basis of
      stress coping ability and the dopamine regulation of aggressive responsiveness.
      The data further indicate that the sympathetic-adreno-medullary axis is directly
      involved in regulating both stress coping strategy and aggressiveness.

PMID- 16978716
TI  - The activation of prefrontal cortical neurons in aggression--a double labeling
      study.
AB  - Violence is associated with prefrontal deficits in humans, suggesting that this
      brain area inhibits aggressiveness. Its role, however, remains controversial, as
      certain subdivisions of the prefrontal cortex become activated by fights in
      rodents. Disparate human findings also show that this area is acutely activated
      by aggression under certain conditions. We explored prefrontal neuronal
      activation patterns in resident rats exposed to psychosocial (sensory contact
      with the intruder) and aggressive encounters. Both psychosocial and aggressive
      encounters increased c-Fos activation in the prelimbic (PrL), anterior cingular
      (Cg1), agranular insular (AI), ventral (VO) and lateral orbital (LO) cortices.
      The infralimbic (IL) and medial orbital (MO) cortices were activated
      significantly by aggressive encounters only. No other prefrontal regions were
      activated by psychosocial or aggressive encounters. The overwhelming majority of
      activated cells were pyramidal (glutamatergic) cells in the Cg1, IL, PrL, MO, and
      VO, whereas interneuron and pyramidal cell activation was similar in AI and LO.
      When rats showed violent aggression, the activation of GABAergic inhibitory cells
      decreased in these two, and two other areas (IL and MO). Notably, the latter two
      areas appeared to be specifically involved in aggressive behavior. The change
      occurred in a recently developed model of violent aggression. In this model,
      pyramidal cell activation in the above mentioned four areas (IL, MO, AI, and LO)
      predicted over 95% of variation in attack counts in general and violent attacks
      in particular. Based on these data, we present a tentative hypothesis on the
      involvement of the prefrontal cortex in the control of aggression.

PMID- 16978717
TI  - Molecular cloning and partial characterization of Babesia equi EMA-3.

PMID- 16978718
TI  - The market for elective surgery: joint estimation of supply and demand.
AB  - This paper develops models of the demand for and supply of elective (non
      emergency) surgery using a panel of quarterly data for 200 English hospitals over
      the period 1995-2002. Unusually, distinct measures of supply (outpatients seen
      and inpatient admissions) and demand (outpatient referrals and decisions to
      admit) are available for each observation. These offer the opportunity to
      estimate separate empirical models of supply and demand using ordinary least
      squares (OLS) regression methods. However, the strong correlation between the
      residuals of these models suggests some merit in the deployment of seemingly
      unrelated regression (SUR) methods. Although both static and dynamic SUR
      estimations leave the results largely qualitatively unchanged, SUR estimation can
      have a considerable quantitative effect relative to the OLS results. For example,
      SUR estimation generates a lower elasticity of inpatient demand with respect to
      waiting time than that obtained via OLS. The results offer an important
      justification for more careful econometric modelling of hospital behaviour than
      has traditionally been employed in the health economics literature.

PMID- 16978719
TI  - What should (public) health insurance cover?
AB  - In any system of health insurance, a decision must be made about what treatments
      the insurance should cover. One way to make this decision is to rank treatments
      by their ratios of health benefits to treatment costs. If treatments that are not
      offered by the health insurance can be purchased out of pocket, the socially
      optimal ranking of treatments to be included in the health insurance is different
      from this standard cost-effectiveness rule. It is no longer necessarily true that
      treatments should be ranked higher the lower are treatment costs (for given
      health benefits). Moreover, the larger are the costs per treatment for a given
      benefit-cost ratio, the higher priority should the treatment be given. If the
      health budget in a public health system does not exceed the socially optimal
      size, treatments with sufficiently low costs should not be performed by the
      public health system if treatment may be purchased privately out of pocket.

PMID- 16978720
TI  - Phase II trial of hypofractionated stereotactic radiotherapy for brain
      metastases: results and toxicity.
AB  - PURPOSE: To prospectively evaluate efficacy and side effects of hypofractionated
      stereotactic radiotherapy (hfSRT) for irresectable brain metastases not amenable
      to radiosurgery (SRS). METHODS AND MATERIALS: From 1/2003 to 2/2005, 51 patients
      with 72 brain metastases were included in a prospective phase II-trial and
      accepted for treatment at the dedicated stereotactic radiosurgery system Novalis
      (BrainLAB, Heimstetten, Germany). In case of planned or prior whole brain
      radiotherapy (WBRT), hfSRT was to be performed with 5 x 6 Gy, otherwise with 5 x
      7 Gy. This dose was prescribed to the 90% isodose line which should cover 100% of
      the planning target volume (PTV). RESULTS: Rates of complete remission (CR),
      partial remission (PR), no change (NC) and progressive disease (PD) were 66.7%,
      18.1%, 12.5% and 2.8%, respectively, after a median follow-up of 7 months. Median
      survival was 11 months. Disease-specific survival and survival related to brain
      metastases were strongly associated with the size of gross tumor volume (GTV),
      the planning target volume (PTV), Karnofsky Performance Score (KPS) and number of
      metastases. Side effects, i.e., increase in T2w-signal area, duration of steroid
      intake and size of new or progressive necrotic centre of metastasis, were
      dependent on the volume of normal brain irradiated with more than 4 Gy per
      fraction (V(4Gy)). Significantly more patients with a V(4Gy)> or =23 cc developed
      radiological signs of side effects from hfSRT. CONCLUSION: Hypofractionated
      stereotactic radiotherapy with 5 x 6-7 Gy is an effective and safe treatment for
      brain metastases not amenable to single high-dose radiosurgery. The normal brain
      volume receiving >4 Gy per fraction may not exceed 20 cc.

PMID- 16978721
TI  - Preclinical safety and antitumor efficacy of insulin combined with irradiation.
AB  - BACKGROUND AND PURPOSE: We have previously reported that insulin significantly
      enhances tumor oxygenation (pO(2)) and increases radiation-induced tumor regrowth
      delay in experimental models. Considering the large radiosensitizing effect,
      clinical trials might be envisioned. The aim of the present pre-clinical study
      was to obtain a more complete set of safety and efficacy data which would further
      justify the commencement of such clinical trials. MATERIAL AND METHODS: Toxicity
      on normal (early and late-responding) tissues was measured by the intestinal
      crypt regeneration assay and the late leg contracture assay. Efficacy in terms of
      enhancement of pO(2) (measured by in vivo EPR oximetry) and increase in radiation
      induced tumor regrowth delay was evaluated with a dose-response study on mice
      bearing FSaII fibrosarcoma. RESULTS: The effect on regrowth delay was directly
      correlated with the effect on the tumor pO(2), with a maximal effect using 400 mU
      kg(-1) insulin. Importantly, there was no increase in the radiation toxicity for
      normal tissues. Finally, we found that the hypoglycaemia induced by insulin can
      be corrected by simultaneous glucose infusion without modification of efficacy.
      CONCLUSION: Insulin here demonstrated a therapeutic gain and a lack of toxicity
      to normal tissues. The results of this study fully justify further larger
      preclinical assays such as the use of fractionated irradiation and a tumor
      control dose assay, before determining the utility of insulin as a
      radiosensitizer for human patients in the clinic.

PMID- 16978722
TI  - Prone breast irradiation for pendulous breasts.
AB  - The purpose of this study was to quantify the differences in doses in the organs
      at risk and to compare the PTV coverage and dose homogeneity of patients with
      pendulous breasts between prone and supine position. In 10 patients a CT-based
      treatment plan was made in prone and supine position. Data about dose homogeneity
      and doses to organs at risk were collected. Dose homogeneity turned out to be
      better in prone position and doses in organs at risk were lower, but with the
      current technique, this occurred at the cost of a reduced PTV coverage.

PMID- 16978723
TI  - Amyloid-beta peptides induce several chemokine mRNA expressions in the primary
      microglia and Ra2 cell line via the PI3K/Akt and/or ERK pathway.
AB  - Alzheimer's disease (AD) is characterized by the presence of senile plaques
      composed primarily of amyloid-beta peptide (Abeta) in the brain. Microglia have
      been reported to surround these Abeta plaques, which have opposite roles,
      provoking a microglia-mediated inflammatory response that contributes to neuronal
      cell loss or the removal of Abeta and damaged neurons. To perform these tasks
      microglia migrate to the sites of Abeta secretion. We herein analyzed the process
      of chemokine expression induced by Abeta stimulation in primary murine microglia
      and Ra2 microglial cell line. We found that Abeta1-42 induced the expressions of
      CCL7, CCL2, CCL3, CCL4 and CXCL2 in the microglia. The signal transduction
      pathway for the expression of CCL2 and CCL7 mRNA induced by Abeta1-42 was found
      to depend on phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal
      regulated kinase (ERK), whereas the pathway for CCL4 depended only on PI3K/Akt.
      These inflammatory chemokine expressions by Abeta stimulation emphasize the
      contribution of neuroinflammatory mechanisms to the pathogenesis of AD.

PMID- 16978724
TI  - Prenatal-through-postnatal exposure to moderate levels of ethanol leads to damage
      on the hippocampal CA1 field of juvenile rats: a stereology and Golgi study.
AB  - Experimental paradigms conducted to assess the neurotoxic effects of ethanol
      exposure on hippocampus development have yielded controversial findings.
      Hippocampal CA1 population and some cytoarchitectural parameters of pyramidal
      cells were studied after exposure to ethanol during early development, in rats.
      Examination of 30-day-old offspring of rats exposed to moderate levels of ethanol
      during gestation through lactation showed an increased volume of the hippocampal
      CA1 field compared to untreated or pair-fed control pups, as well as a reduced
      number of pyramidal neurons. In addition, the number of spines from surviving CA1
      pyramidal neurons was reduced. Furthermore, stubby and wide spines were
      proportionally increased, while the proportion of mushroom and ramified spines
      was reduced; no variation in the proportion of thin spines was observed. Because
      alcoholic women usually drink alcohol before, during, and after pregnancy, a
      broad-range experimental model of alcohol exposure was used in this study. The
      present findings show that experimental exposure to moderate levels of ethanol,
      resembling the human situation in alcoholic mothers, leads to loss of hippocampal
      CA1 pyramidal neurons, along with several pathological and plastic events in the
      dendritic arborization of these neurons. Some ethanol-induced excitotoxicity
      related mechanisms, which may be underlying these effects, are discussed.

PMID- 16978725
TI  - Effect of environmental parameters on growth kinetics of Bacillus cereus (ATCC
      7004) after mild heat treatment.
AB  - The influence of temperature (10 to 50 degrees C), initial pH (4.0 to 6.0) and
      sodium chloride concentration (0.5 to 3.0%) on the growth in nutrient broth and
      in meat extract of Bacillus cereus after mild heat treatment (90 degrees C--10
      min) was determined. B. cereus spores survived after heating and they were able
      to germinate and grow in both media when post-treatment conditions were
      favourable. Heated B. cereus did not grow at 10 and 50 degrees C or in a medium
      with pH 4.0. Decreasing pH values and increasing levels of sodium chloride
      decreased growth rate and increased the lag phase of B. cereus. pH 4.5 was unable
      to prevent the growth of heated spores in a meat substrate with 0.5% NaCl at 12
      degrees C. The combination of pH </=4.5, NaCl concentration >/=1.0% and
      temperatures </=12 degrees C was sufficient to inhibit B. cereus growth after
      heat treatment at 90 degrees C for 10 min, for at least 50 days in nutrient broth
      and in meat extract. Re-heating at temperatures >/=60 degrees C could control
      heated B. cereus ATCC 7004 growth.

PMID- 16978726
TI  - Magnetocapture of abalone transcription factor NF-kappaB: a new strategy for
      isolation and detection of NF-kappaB both in vitro and in vivo.
AB  - Rel?NF-kappaB plays an important role in the immune response. Recently, a
      homologue of Rel?NF-kappaB transcription factor was identified from a gastropod
      abalone, Haliotis diversicolor supertexta, named Ab-Rel. We present here a new
      strategy, so called magnetocapture, based on magnetic separation that was
      developed to isolate and detect this abalone transcriptional factor. With this
      method, Ab-Rel was successfully isolated from abalone haemocytes and the
      recombinant Ab-Rel protein from an insect cell line. Western blot analysis was
      performed to verify the effectiveness of this magnetocapture assay. Since only
      the activated NF-kappaB can be captured and separated from the whole cell
      extracts, this method was simultaneously used to detect the NF-kappaB activity in
      vivo, as well as the biological activity of the recombinant protein in vitro. In
      addition, several proteins which might interact with the abalone NF-kappaB were
      together isolated, suggesting that the magnetocapture method would be useful for
      identifying interaction molecules. These results illustrated that the
      magnetocapture strategy is rapid, reliable and versatile, providing a promising
      tool for studying Rel?NF-kappaB protein.

PMID- 16978727
TI  - A kinetic-dynamic model for regulatory RNA processing.
AB  - A kinetic-dynamic model was proposed to simulate RNA processing by determining
      four essential reaction rates, including the rates of transcription, pre-mRNA
      turnover, pre-mRNA splicing, and mRNA decay. A family competition evolutionary
      algorithm (FCEA) was adapted herein to approximate these rates. Several
      artificial datasets were used to verify the correctness and robustness of the
      FCEA. The model was finally applied on time series data of yeast prp4-l mutant
      cells for determination of rates of RNA processing. Based on the FCEA, the model
      indicated that the pre-mRNA splicing was decreased in the mutant cells as well as
      the possible effects on transcription, pre-mRNA turnover, and mRNA decay, which
      was consistent with surveyed literature.

PMID- 16978728
TI  - Did brain-specific genes evolve faster in humans than in chimpanzees?
AB  - One of the most distinctive characteristics of humans among primates is the size,
      organization and function of the brain. A recent study has proposed that there
      was widespread accelerated sequence evolution of genes functioning in the nervous
      system during human origins. Here we test this hypothesis by a genome-wide
      analysis of genes that are expressed predominantly or specifically in brain
      tissues and genes that have important roles in the brain, identified on the basis
      of five different definitions of brain specificity. Although there is little
      overlap among the five sets of brain-specific genes, none of them supports human
      acceleration. On the contrary, some datasets show significantly fewer
      nonsynonymous substitutions in humans than in chimpanzees for brain-specific
      genes relative to other genes in the genome. Our results suggest that the unique
      features of the human brain did not arise by a large number of adaptive amino
      acid changes in many proteins.

PMID- 16978729
TI  - Detection and validation of the body edge in low count emission tomography
      images.
AB  - Segmentation of the body edge in tomographic images with low count, noisy edges
      is needed for both PET and SPECT respiratory motion correction and brain SPECT
      attenuation correction. To reduce noise we re-projected tomographic images and
      searched for edges in the projection count profiles or their spatial derivatives.
      Edge location versus projection angle was fitted with cosine basis functions
      after rejecting outliers and including information about edges of previous
      sections. We processed 10 s duration FDG PET of the thorax, HMPAO brain, DAT
      brain and lung perfusion SPECT. Stable edges for all four types of scan were
      achieved but with different profiles. Edges were validated against edges of
      coregistered CT or MRI. The best root mean square (rms) accuracy was 8.2 mm (PET)
      and 5.2 mm (brain SPECT). Inter-scan variability (standard deviation) in the
      estimated-to-control edge distance for 17 PET scans was 0.4 mm, for 25 ordered
      subset expectation maximisation (OSEM) reconstructed brain SPECT 1.0 mm and for
      18 filtered back-projection (FBP) reconstructed brain SPECT 1.4 mm.

PMID- 16978730
TI  - Compensation for age-associated chemosensory losses and its effect on the
      pleasantness of a custard dessert and a tomato drink.
AB  - Differences between elderly subjects (n=52, 60-85 years) and young subjects
      (n=55, 18-35) in their food liking and their olfactory capability were
      investigated. Two food systems were used: custard desserts and tomato drinks.
      Flavor enhancement/enrichment, textural change, and/or irritant addition were
      incorporated as compensatory strategies into these foods. The addition of low
      concentrations of both cherry flavor and cream flavor to the custard desserts
      influenced their pleasantness for the majority of the elderly. The addition of
      cream topping increased the pleasantness of the custard desserts for both the
      elderly and the young. The elderly equally liked the tomato drinks with no or
      with low irritant addition, whereas the young generally disliked an irritant
      addition. However, the food liking of the elderly was not generally increased by
      these different compensatory strategies. Instead, subgroups were observed for
      each compensatory strategy, in which applied compensatory strategies led to an
      increase in product pleasantness. Age-associated losses in olfactory capabilities
      did not sufficiently explain differences in food liking, as only elderly with
      similar olfactory capabilities to the young demonstrated a liking of enhanced
      flavor. The present study does not support the assumption that age-associated
      impairment in olfactory capability will inevitably lead to changes in food
      liking.

PMID- 16978731
TI  - Risk of MRSA transmission from tourniquets.

PMID- 16978732
TI  - Accuracy of economic studies on surgical site infection.
AB  - Estimating the cost of hospital infection has become a matter of increasing
      interest in terms of health economics. This study aimed to assess the accuracy of
      economic studies on hospital infections, using surgical site infection (SSI) as
      an example. A search was performed for original articles reporting the cost of
      SSI, published in the English language between 1996 and 2005. For the critical
      review, the period of cost tracking, classification of costs and cost counting
      methods were noted. Fifteen articles met the inclusion criteria. The costs of SSI
      vary according to surgical procedures, country, publication year, study design
      and accounting method. Only two studies estimated the additional cost of SSI
      after discharge. All 15 studies included healthcare costs and none measured
      patient/family resources. In 10 studies, the costs were calculated based on
      accounting. Three studies used estimated costs from the ratio of costs to charges
      and two studies used charge data in place of cost data. It will become
      increasingly important for future studies to perform multi-centre prospective
      surveys, establish a standard method for cost accounting, include the cost of
      healthcare services following hospitalization and consider the morbidity cost to
      patients themselves from a societal perspective.

PMID- 16978733
TI  - Increased mortality among elderly patients with meticillin-resistant
      Staphylococcus aureus bacteraemia.
AB  - Despite the high prevalence of meticillin-resistant Staphylococcus aureus (MRSA)
      infections among the elderly, outcomes of nosocomial MRSA bloodstream infections
      (BSI) for this patient population have not been fully examined. We performed a
      case-control study to compare outcomes of hospital-acquired MRSA BSI among
      patients >/=65 years of age (cases) with those younger than 65 years of age
      (controls). In a 430-bed tertiary-care teaching hospital, 100 hospitalized
      patients >/=18 years of age with S. aureus BSI were included in the study.
      Measurements obtained were: comorbidities, severity of illness at presentation,
      antibiotic therapy, haematogenous complications and mortality. Overall mortality
      was significantly higher among cases than controls [36% vs 12%; odds ratio (OR)
      4.1, 95% confidence interval (CI) 1.4-14, P<0.01]. A pulmonary source was
      identified more frequently among elderly patients compared with younger controls
      (34% vs 16%; OR 2.7, 95%CI 1.1-8.1, P=0.04). On logistic regression, the
      following variables were independently associated with MRSA BSI among elderly
      patients: admission to a medical ward (OR 3.1, 95%CI 1.3-7.6, P=0.02), non
      central-venous-catheter-related BSI (OR 3, 95%CI 1.2-7.6, P=0.02) and death (OR
      3.7, 95%CI 1.3-11, P=0.02). Among patients who received vancomycin, more cases
      were treated with a reduced dose of vancomycin due to renal insufficiency
      compared with controls (64% vs 31%; OR 4, 95%CI 2-9, P=0.01). These data suggest
      that MRSA BSI is associated with significant mortality among the elderly
      population. Preventing MRSA acquisition among this patient population is of
      paramount importance.

PMID- 16978734
TI  - MRSA behind bars? Or out on parole?

PMID- 16978735
TI  - Outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae
      infection among renal transplant recipients.

PMID- 16978736
TI  - An outbreak of Acinetobacter baumannii in an intensive care unit: epidemiological
      and molecular findings.

PMID- 16978737
TI  - National variability in out-of-hospital treatment after traumatic injury.
AB  - STUDY OBJECTIVE: The optimal out-of-hospital treatment for trauma patients
      remains a subject of national debate. Researchers designing future studies to
      address these issues must understand the variability in treatment that exists
      across the United States. We define the variability in the out-of-hospital
      treatment provided to trauma patients in the United States. METHODS: This was a
      retrospective analysis of prospectively collected data for a cohort study of
      trauma outcomes. The study was conducted at 15 urban or suburban regions across
      the United States, 18 Level I trauma centers and 51 nontrauma centers. We used a
      weighted population sample based on data from all hospital trauma deaths and a
      sample of patients discharged between January 2001 and December 2002. Entry
      criteria included at least 1 body region with an Abbreviated Injury Score greater
      than 3 and age between 18 and 84 years. Exclusion criteria were patient age
      greater than 65 years and isolated hip fractures and patients with burns.
      RESULTS: Complete out-of-hospital data were available for 3,357 patients,
      representing a weighted population sample of 9,929 patients. Out-of-hospital
      treatment varied substantially among the regions, including out-of-hospital
      intubation (5% to 48%), use of neuromuscular blocking agents or sedatives to
      facilitate intubation (0% to 100%), surgical airway access (0.1% to 3.5%),
      peripheral and central intravenous access (22% to 95%), and needle thoracentesis
      (0% to 5%). CONCLUSION: There is considerable national variability in out-of
      hospital procedures performed for trauma patients.

PMID- 16978738
TI  - The diagnostic accuracy of 64-slice computed tomography coronary angiography
      compared with stress nuclear imaging in emergency department low-risk chest pain
      patients.
AB  - STUDY OBJECTIVE: We compared the accuracy of multidetector computed tomography
      (CT) coronary angiography with stress nuclear imaging for the detection of an
      acute coronary syndrome or 30-day major adverse cardiac events in low-risk chest
      pain patients. METHODS: This was a prospective study of the diagnostic accuracy
      of myocardial perfusion imaging and multidetector CT in low-risk chest pain
      patients. The target condition was an acute coronary syndrome (confirmed >70%
      coronary stenosis on coronary artery catheterization) or major adverse cardiac
      events within 30 days. Patients were low risk by Reilly/Goldman criteria and had
      negative serial ECGs and cardiac markers. All had both rest/stress sestamibi
      nuclear imaging and multidetector CT. Patients with abnormal stress nuclear
      imaging results (reversible perfusion defects) or multidetector CT results
      (stenosis >50% or calcium score >400) were considered for cardiac
      catheterization, and those with discordant results had a greater than 30-day
      reevaluation (including ECG) by a cardiologist. All were followed up for evidence
      of major adverse cardiac events within 30 days by review of hospital records and
      structured telephone interview. Primary outcomes were the accuracy of
      multidetector CT and myocardial perfusion imaging for the detection of an acute
      coronary syndrome and 30-day major adverse cardiac events. RESULTS: Of the 92
      patients, 7 (8%) were excluded because of uninterpretable multidetector CT scans.
      Of the remaining 85 study patients (49+/-11 years, 53% men), 7 (8%) were found to
      have the target condition, with all having significant coronary stenosis (88%+/
      9%) and none having myocardial infarction or major adverse cardiac events during
      30 days. Stress nuclear imaging results were negative in 72 (85%) patients, and
      multidetector CT results were negative in 73 (86%) patients. The sensitivity of
      stress nuclear imaging was 71% (95% confidence interval [CI] 36% to 92%), and
      multidetector CT was 86% (95% CI 49% to 97%), and the specificity was 90% (95% CI
      81% to 95%) and 92% (95% CI 84% to 96%), respectively. The negative predictive
      value of stress nuclear imaging and multidetector CT was 97% (95% CI 90% to 99%)
      and 99% (95% CI 93% to 100%), respectively, and the positive predictive value was
      38% (95% CI 18% to 64%) and 50% (95% CI 25% to 75%), respectively. CONCLUSION:
      The accuracy of multidetector CT is at least as good as that of stress nuclear
      imaging for the detection and exclusion of an acute coronary syndrome in low-risk
      chest pain patients.

PMID- 16978739
TI  - Randomized double-blind placebo-controlled trial of two intravenous morphine
      dosages (0.10 mg/kg and 0.15 mg/kg) in emergency department patients with
      moderate to severe acute pain.
AB  - STUDY OBJECTIVE: We compare pain relief and safety of morphine 0.10 mg/kg with
      0.15 mg/kg in adult emergency department (ED) patients with acute pain. METHODS:
      This was a randomized double-blind placebo-controlled trial of intravenous
      morphine 0.10 mg/kg versus 0.15 mg/kg, (delivered in 2 divided doses) in adult ED
      patients with acute pain requiring opioid analgesia. Assessment was made at
      baseline, 30 minutes, and 60 minutes with a validated verbal numeric rating
      scale. Pain reduction and satisfaction scores were measured at 30 and 60 minutes.
      The primary outcome measure was the between-group difference in mean before-after
      change in numeric rating scale from baseline to 60 minutes. RESULTS: Two hundred
      eighty patients were enrolled. Between-group difference in numeric rating scale
      improvement from baseline to 60 minutes was 0.8 (95% confidence interval 0.1 to
      1.5), favoring the 0.15 mg/kg group. Pain relief scores and adverse events were
      similar in the 2 groups. CONCLUSION: Although 0.15 mg/kg of morphine is safe and
      provides statistically superior analgesia compared with a dose of morphine at
      0.10 mg/kg, this difference in pain reduction did not reach the threshold of
      greater than 1.3 numeric rating scale units required to declare the higher dose
      of morphine clinically superior.

PMID- 16978740
TI  - From submission to publication: a retrospective review of the tables and figures
      in a cohort of randomized controlled trials submitted to the British Medical
      Journal.
AB  - STUDY OBJECTIVE: We characterize the quantity and quality of data tables and
      figures in reports of randomized controlled trials (RCTs) submitted to the
      British Medical Journal (BMJ) and published in peer-reviewed journals. We
      investigate how the peer review process affected table and figure quality.
      METHODS: We reviewed 62 consecutive reports of RCTs submitted to the BMJ in 2001
      that were later published in the BMJ (n=12) or elsewhere. We counted and
      categorized the tables and figures in both the initial submissions and published
      articles. Using standardized instruments and procedures, we analyzed the quality
      of these tables and figures and checked BMJ editorial documents to see whether
      changes were triggered by their review process. RESULTS: The numbers of tables
      and figures did not change markedly between submission and publication. Five
      percent of publications had no data tables; 56% had no data figures. Data density
      was low for published tables and figures. Tables seldom showed data stratified on
      important covariates; 88% of published tables were simple lists or were
      stratified on only 1 variable. Less than half the figures met their data
      presentation potential, with most failing to portray by-subject data and few
      displaying advanced features such as pairing, symbolic dimensionality, or small
      multiples. BMJ external peer reviewers seldom commented on tables or figures.
      CONCLUSION: Tables and figures can convey details and complex relationships not
      easily described in text. Although tables are included in most submitted and
      published articles, they are not presented optimally; figures are used sparingly
      and are also of suboptimal quality. Journals should consider improving their
      table and figure quality in the hope that improved graphics will empower readers
      to scrutinize the data, thereby dissuading authors from presenting biased
      analyses and misrepresented conclusions.

PMID- 16978741
TI  - The utility of supplemental oxygen during emergency department procedural
      sedation and analgesia with midazolam and fentanyl: a randomized, controlled
      trial.
AB  - STUDY OBJECTIVE: To determine whether supplemental oxygen reduces the incidence
      of hypoxia by 20% in study patients receiving midazolam and fentanyl for
      emergency department procedural sedation and analgesia. METHODS: Patients were
      randomized to receive either supplemental oxygen or compressed air by nasal
      cannula at 2 L per minute. Physicians were blinded to the gas used and end-tidal
      carbon dioxide (ETCO2) data. Respiratory depression was defined a priori as
      oxygen saturation less than 90%, ETCO2 level greater than 50 mm Hg, an absolute
      change from baseline of 10 mm Hg, or loss of the ETCO2 waveform. RESULTS: Of the
      80 patients analyzed, 44 received supplemental oxygen and 36 received compressed
      air. Twenty supplemental oxygen patients and 19 compressed air patients met at
      least 1 criterion for respiratory depression. Six supplemental oxygen patients
      and 5 compressed air patients experienced hypoxia (P=.97; effect size 0%; 95%
      confidence interval -15% to +15%). Fourteen patients in each group met ETCO2
      criteria for respiratory depression but were not hypoxic. Physicians identified
      respiratory depression in 8 of 11 patients who became hypoxic and 0 of 28
      patients who met ETCO2 criteria for respiratory depression but who did not become
      hypoxic. There were no adverse events. CONCLUSION: Supplemental oxygen did not
      reduce (or trend toward reducing) the incidence of hypoxia in patients moderately
      sedated with midazolam and fentanyl. However, our lower-than-expected rate of
      hypoxia limits the power of this comparison. Blinded capnography frequently
      identified respiratory depression undetected by the treating physicians.

PMID- 16978742
TI  - The serine protease Omi/HtrA2 is involved in XIAP cleavage and in neuronal cell
      death following focal cerebral ischemia/reperfusion.
AB  - Omi/HtrA2 is a pro-apoptotic mitochondrial serine protease involved in both forms
      of apoptosis, caspase-dependent as well as caspase-independent cell death.
      However, the impact of Omi/HtrA2 in the apoptotic cell machinery that takes place
      in vivo under pathological conditions such as cerebral ischemia remains unknown.
      The present study was monitored in order to examine whether Omi/HtrA2 plays a
      decisive role in apoptosis observed after focal cerebral ischemia in rats. Male
      adult rats were subjected to 90min of focal cerebral ischemia followed by
      reperfusion and treated with vehicle or ucf-101, a novel and specific Omi/HtrA2
      inhibitor, prior reperfusion. Focal cerebral ischemia/reperfusion induced a
      mitochondrial up-regulation of Omi/HtrA2 and significantly increased cytosolic
      accumulation of Omi/HtrA2. Furthermore, ischemia led to activation of caspase-3
      and degradation X-linked inhibitor of apoptosis protein (XIAP). Treatment of
      animals prior ischemia with ucf-101, the specific inhibitor of Omi/HtrA2, was
      able to (1) reduce the number of TUNEL-positive cells, to (2) attenuate the XIAP
      breakdown and to (3) reduce the infarct size. This study shows for the first time
      that focal cerebral ischemia in rats results in Omi/HtrA2 translocation from the
      mitochondria to the cytosol, where it participates in neuronal cell death.
      Blocking the proteolytic activity of Omi/HtrA2 with specific inhibitors, such as
      the ucf-101, could be a novel way to afford neuroprotection and minimize cellular
      damage in cerebral ischemia/reperfusion.

PMID- 16978743
TI  - Parkinson's disease genetic mutations increase cell susceptibility to stress:
      mutant alpha-synuclein enhances H2O2- and Sin-1-induced cell death.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative movement disorder
      characterized by selective loss of dopaminergic neurons and the presence of Lewy
      bodies. Alpha-synuclein is a major component of Lewy bodies in sporadic PD, and
      genetic alterations in alpha-synuclein cause autosomal-dominant hereditary PD.
      The pathogenesis of PD remains incompletely understood, but it appears to involve
      both genetic susceptibility and environmental factors. Here we investigated the
      effect of alpha-synuclein expression on cell susceptibility to proteasome
      inhibition, oxidative and nitrative stresses by using a PC 12-Tet-off regulatory
      system. We found that inducible expression of A30P or A53T mutant alpha-synuclein
      decreased the proteasome activity, increased intracellular ROS levels, and
      enhanced lactacystin- and H2O2-induced cell death. Furthermore, 3-nitrotyrosine
      levels increased in cells expressing alpha-synuclein, and further increased after
      Sin-1 (a NO donor) treatment compared with untreated or treated non-induced
      cells. Expression of alpha-synuclein (mutant more than wild type) significantly
      enhances Sin-1 toxicity. These results indicate that genetic mutations in alpha
      synuclein may increase neuronal vulnerability to cellular stress in aging and PD
      pathogenesis.

PMID- 16978744
TI  - [Helicobacter pylori prevalence in Raynaud's disease].
AB  - PURPOSE: Recent studies have suggested that the prevalence of Helicobacter pylori
      may be more frequent in patients with primary Raynaud's phenomenon (PRP) compared
      to healthy subjects. These data prompted us to conduct this prospective study, in
      order to assess the prevalence of H. pylori infection in a large series of
      patients with PRP. METHODS: Forty consecutive patients with a definite diagnosis
      of PRP were included in the study. The findings in the PRP patients were compared
      with those of 80 age- and sex-matched healthy subjects. H. pylori infection was
      diagnosed using serology and urease breath test. RESULTS: The prevalence of H.
      pylori infection was as high as 12.5% in PRP patients using both serology and
      urease breath test, whereas it was found to be 16.7% and 18%, respectively, in
      healthy controls. CONCLUSION: As prevalence of H. pylori infection was similar in
      PRP patients compared to controls (P=0.53 and 0.43, respectively), our data
      underscore that H. pylori infection may not play a role in the genesis of PRP
      related vascular complication onset. Interestingly, PRP patients exhibited more
      commonly digestive symptoms consistent with H. pylori infection compared to
      controls (P<0.05).

PMID- 16978745
TI  - [The MYH9 syndrome: report of a new case with a new mutation of the MYH9 gene].
AB  - INTRODUCTION: Familial macrothrombocytopenias are a group of rare autosomal
      dominant platelet disorders including many syndromes in particular the May
      Hegglin anomaly. They are characterized by thrombocytopenia with giant platelets
      and in some cases neutrophilic inclusions in peripheral blood granulocytes.
      Recently these different clinical entities have been demonstrated to be linked to
      mutations in the same gene, MYH9. CASE REPORT: We report in a young African woman
      presenting as a May-Hegglin anomaly a new mutation of the MYH9 gene. In regard of
      this case we present a brief review of the MYH9 syndrome. CONCLUSION: The MYH9
      syndrome includes now several clinical entities who share some common clinical
      and biological characteristics such as a thrombocytopenia with giant platelets,
      presence or absence of other manifestations including Dohle like bodies,
      nephritis, sensorineural hearing loss, cataract. We report a new case in which a
      new mutation of the MYH9 gene was evidenced.

PMID- 16978746
TI  - [Pasteurella dagmatis spondylodiscitis in a diabetic patient].
AB  - INTRODUCTION: Healthy pets contact are able to induce unusual and severe
      diseases. CLINICAL CASE: This case reports the medical history of a dorsal
      spondylodiscitis in a diabetic patient admitted for a chronic wound of his toes.
      He had a long-standing history of regular consumption of alcohol and tobacco.
      Blood bottles and biopsy of intervertebral disc infected discovered Pasteurella
      dagmatis, commonly colonizing the oropharynx of healthy dogs and cats. In this
      case, licking of his injured toe by his dog was the likely source of entry of the
      organism. DISCUSSION: We found no identical cases in the medical literature.
      Diabetes mellitus and other immunocompromised disorders justify to change
      behaviours toward domestic animals.

PMID- 16978747
TI  - [Basedow's disease and celiac disease in an adolescent with Down syndrome].
AB  - INTRODUCTION: Down syndrome is a favourable land to the emergence of auto-immune
      disease. CASE RECORD: Graves' disease and celiac disease were diagnosed in a 16
      years old adolescent with Down syndrome presenting chronic diarrhoea, important
      delayed development and signs of hyperthyroidism. DISCUSSION: Celiac disease and
      thyroid dysfunction would be screening in patient with Down syndrome.

PMID- 16978748
TI  - Multiple closed flexor tendon avulsions from their insertions by a high-energy
      explosion.

PMID- 16978749
TI  - Investigation of organochlorine pesticides (OCPs) in mollusks collected from
      coastal sites along the Chinese Bohai Sea from 2002 to 2004.
AB  - Mollusks living in seas can accumulate organochlorine pesticides (OCPs). The
      residue levels of selected OCPs: dichlorodiphenyltrichloroethane (p,p'-DDT, o,p'
      DDT, p,p'-DDE, p,p'-DDD), hexachlorocyclohexanes (alpha-, beta-, gamma- and delta
      HCH) in gastropod and bivalve species collected from ten coastal cites along the
      Chinese Bohai Sea were investigated from 2002 to 2004. The species included nine
      kinds of mollusks: Rapana venosa, Neverita didyma, Scapharca subcrenata, Mytilus
      edulis, Amusium, Crassostrea talienwhanensis, Meretix meretrix, Sinonovacula
      constricta, Ruditapes philippinarum, Mactra veneriformis. The results showed that
      OCPs widely existed in the mollusks organisms. p,p'-DDT, p,p'-DDE, beta-HCH were
      the major compounds. Statistical analysis (One-way ANOVA) showed that the
      contents of OCPs in these mollusks did not change obviously from 2002 to 2004.
      Principal component analysis (PCA) was also used for determining the polluting
      characters existing in this selected field.

PMID- 16978750
TI  - Formative research on adolescent and adult perceptions of risk factors for breast
      cancer.
AB  - This study uses the Health Belief Model (HBM) as a framework to guide formative
      research of the lay public's perceptions of risks associated with breast cancer.
      Data were collected from adolescent females and adult females across four
      counties in Michigan, US. Ten focus groups (N=91) were conducted and analyzed
      with a coding scheme based on the HBM. Participants' responses to focus group
      questions (N=5168 thought units) reveal beliefs about severity, susceptibility,
      and efficacy pertaining to breast cancer, nutrition, activity, environment, and
      the role of government and industry. Chi-squares examined the distribution of
      statements across categories between adult females and adolescent females.
      Results revealed that both adolescent and mother groups recognized gender and
      heredity as relevant risk factors related to susceptibility, and detection as a
      strategy to decrease severity of breast cancer through early treatment. Beliefs
      about environmental factors were characterized by uncertainty for both groups.
      Also, while adolescent girls communicated more about efficacy issues, mothers
      focused significantly more than adolescent girls on the role of government and
      industry in breast cancer prevention and treatment. Representative qualitative
      thought units are included based on their frequency, salience, and relevance to
      HBM message design guidelines. Formative research is the first phase in the
      development of health campaigns, informing the creation of health messages for
      target audiences.

PMID- 16978751
TI  - Responding to global infectious disease outbreaks: lessons from SARS on the role
      of risk perception, communication and management.
AB  - With increased globalisation comes the likelihood that infectious disease
      appearing in one country will spread rapidly to another, severe acute respiratory
      syndrome (SARS) being a recent example. However, although SARS infected some
      10,000 individuals, killing around 1000, it did not lead to the devastating
      health impact that many feared, but a rather disproportionate economic impact.
      The disproportionate scale and nature of this impact has caused concern that
      outbreaks of more serious disease could cause catastrophic impacts on the global
      economy. Understanding factors that led to the impact of SARS might help to deal
      with the possible impact and management of such other infectious disease
      outbreaks. In this respect, the role of risk--its perception, communication and
      management--is critical. This paper looks at the role that risk, and especially
      the perception of risk, its communication and management, played in driving the
      economic impact of SARS. It considers the public and public health response to
      SARS, the role of the media and official organisations, and proposes policy and
      research priorities for establishing a system to better deal with the next global
      infectious disease outbreak. It is concluded that the potential for the rapid
      spread of infectious disease is not necessarily a greater threat than it has
      always been, but the effect that an outbreak can have on the economy is, which
      requires further research and policy development.

PMID- 16978752
TI  - Fatal agranulocytosis: the use of olanzapine in a patient with schizophrenia and
      myelodysplasia.
AB  - Neutropenia and agranulocytosis are risks known to occur with phenothiazines and
      clozapine. The mechanisms responsible for these conditions currently remain
      unclear. To our knowledge, no case of fatal agranulocytosis as a result of
      olanzapine treatment was reported in the literature. Thus any case of severe
      neutropenia occurring in a patient receiving olanzapine is alarming to
      clinicians. First, a review of the literature produced 41 anecdotic cases of
      neutropenia or agranulocytosis during treatment with olanzapine (Zyprexa)
      reported in a total of 24 publications. Second, we report a case of neutropenia,
      which proved to be fatal in a schizophrenia patient receiving olanzapine and
      thiazide. The cause of the death was Myelodysplastic syndrome. There is not
      enough evidence to prove the involvement of either olanzapine or
      hydrochlorothiazide or the interaction between them in this patient's
      myelodysplasia. Bone marrow cytogenetic study confirmed the deletion of the long
      arm of chromosome 11, as reported in myeloid leukemia. If this patient would have
      died suddenly without the laboratory investigations that lead to the diagnosis of
      myeloblastic leukemia, the cause would have been probably and wrongfully allotted
      to treatment with olanzapine.

PMID- 16978754
TI  - Challenging the unipolar-bipolar division: does mixed depression bridge the gap?
AB  - BACKGROUND: Mixed states, i.e., opposite polarity symptoms in the same mood
      episode, question the categorical splitting of mood disorders in bipolar
      disorders and unipolar depressive disorders, and may support a continuum between
      these disorders. Study aim was to find if there were a continuum between
      hypomania (defining BP-II) and depression (defining MDD), by testing mixed
      depression as a 'bridge' linking these two disorders. A correlation between
      intradepressive hypomanic symptoms and depressive symptoms could support such a
      continuum, but other explanations of a correlation are possible. METHODS:
      Consecutive 389 BP-II and 261 MDD major depressive episode (MDE) outpatients were
      interviewed, cross-sectionally, with the Structured Clinical Interview for DSM
      IV, the Hypomania Interview Guide (to assess intradepressive hypomanic symptoms)
      and the Family History Screen, by a mood disorders specialist psychiatrist in a
      private practice. Patients presented voluntarily for treatment of depression when
      interviewed drug-free and had many subsequent follow-ups after treatment start.
      Mixed depression (depressive mixed state) was defined as the combination of MDE
      (depression) and three or more DSM-IV intradepressive hypomanic symptoms
      (elevated mood and increased self-esteem were always absent by definition), a
      definition validated by Akiskal and Benazzi. RESULTS: BP-II, versus MDD, had
      significantly lower age at onset, more recurrences, atypical and mixed
      depressions, bipolar family history, MDE symptoms and intradepressive hypomanic
      symptoms. Mixed depression was present in 64.5% of BP-II and in 32.1% of MDD
      (p=0.000). There was a significant correlation between number of MDE symptoms and
      number of intradepressive hypomanic symptoms. A dose-response relationship
      between frequency of mixed depression and number of MDE symptoms was also found.
      CONCLUSIONS: Differences on classic diagnostic validators could support a
      division between BP-II and MDD. Presence of intradepressive hypomanic symptoms by
      itself, and correlation between intradepressive hypomanic symptoms and depressive
      symptoms could instead support a continuum. Other explanations of such a
      correlation are possible. Depending on the method used, a BP-II-MDD continuum
      could be supported or not.

PMID- 16978753
TI  - Effects of topiramate on methamphetamine-induced changes in attentional and
      perceptual-motor skills of cognition in recently abstinent methamphetamine
      dependent individuals.
AB  - Methamphetamine-dependent individuals often cite the need to maintain enhanced
      cognitive performance and attention as a reason for continuing or relapsing to
      drug-taking. Further, methamphetamine addicts might not comply with taking a
      potentially therapeutic medication if it had a profound effect on these cognitive
      processes. Topiramate, a sulfamate-substituted fructopyranose derivative, has
      been suggested as a putative therapeutic medication for treating methamphetamine
      dependence. Examination of topiramate's effects on cognitive performance and
      attention is a clinically and scientifically important component of understanding
      its potential therapeutic profile. In 10 male and female individuals who met DSM
      IV criteria for methamphetamine dependence, we examined the effects of low (50 mg
      b.i.d.)- and high (100 mg b.i.d.)-dose topiramate - in both the presence and
      absence of low (15 mg)- and high (30 mg)-dose intravenous methamphetamine--on
      cognitive performance, attention, and concentration on the rapid visual
      information processing task and the digit symbol substitution test. Intravenous
      methamphetamine enhanced cognitive performance, attention, and concentration
      among recently withdrawn methamphetamine addicts--an effect that hitherto had not
      been well characterized. Topiramate's cognitive effects were mixed and rather
      paradoxical, with a tendency to improve attention and concentration both alone
      and in the presence of methamphetamine while worsening psychomotor retardation.
      No deleterious interaction occurred between topiramate and methamphetamine on any
      of these cognitive processes. While clinical studies with topiramate should
      prepare participants for possible psychomotor retardation, the cognitive effects
      profile observed would not likely present an important obstacle to compliance in
      motivated patients. Topiramate's complicated cognitive effects among
      methamphetamine addicts need more comprehensive examination.

PMID- 16978755
TI  - Absorption, accumulation and biological effects of depleted uranium in Peyer's
      patches of rats.
AB  - The digestive tract is the entry route for radionuclides following the ingestion
      of contaminated food and/or water wells. It was recently characterized that the
      small intestine was the main area of uranium absorption throughout the
      gastrointestinal tract. This study was designed to determine the role played by
      the Peyer's patches in the intestinal absorption of uranium, as well as the
      possible accumulation of this radionuclide in lymphoid follicles and the
      toxicological or pathological consequences on the Peyer's patch function
      subsequent to the passage and/or accumulation of uranium. Results of experiments
      performed in Ussing chambers indicate that the apparent permeability to uranium
      in the intestine was higher (10-fold) in the mucosa than in Peyer's patches
      ((6.21+/-1.21 to 0.55+/-0.35)x10(-6)cm/s, respectively), demonstrating that the
      small intestinal epithelium was the preferential pathway for the transmucosal
      passage of uranium. A quantitative analysis of uranium by ICP-MS following
      chronic contamination with depleted uranium during 3 or 9 months showed a
      preferential accumulation of uranium in Peyer's patches (1355% and 1266%,
      respectively, at 3 and 9 months) as compared with epithelium (890% and 747%,
      respectively, at 3 and 9 months). Uranium was also detected in the mesenteric
      lymph nodes ( approximately 5-fold after contamination with DU). The biological
      effects of this accumulation of depleted uranium after chronic contamination were
      investigated in Peyer's patches. There was no induction of the apoptosis pathway
      after chronic DU contamination in Peyer's patches. The results indicate no change
      in the cytokine expression (Il-10, TGF-beta, IFN-gamma, TNF-alpha, MCP-1) in
      Peyer's patches and in mesenteric lymph nodes, and no modification in the uptake
      of yeast cells by Peyer's patches. In conclusion, this study shows that the
      Peyer's patches were a site of retention for uranium following the chronic
      ingestion of this radionuclide, without any biological consequences of such
      accumulation on Peyer's patch functions.

PMID- 16978756
TI  - Toxicity of hexachlorobenzene and its transference from microalgae (Chlorella
      kessleri) to crabs (Chasmagnathus granulatus).
AB  - The aim of this work was to study the transference of hexachlorobenzene from a
      green alga (Chlorella kessleri) to an estuary crab (Chasmagnathus granulatus),
      and to analyze the toxic effects that the xenobiotic has on the latter. The
      effect of hexachlorobenzene uptake was evaluated measuring oxidative stress,
      Uroporphyrinogen decarboxylase activity and morphometric parameter alteration,
      and also performing a histological analysis of crab hepatopancreas. Results
      demonstrated that hexachlorobenzene enters the alga, is accumulated in it, and
      then transferred into the crab, causing a decrease in Uroporphyrinogen
      decarboxylase activity in both organisms. The high malondialdehyde levels
      detected in crab hepatopancreas after the toxic treatment suggested the existence
      of hexachlorobenzene-induced lipid peroxidation. Antioxidant defenses such as
      superoxide dismutase activity and reduced glutathione content fell below normal
      values on the fourth week of treatment. At the same time, the hepatosomatic
      index, used as a morphometric parameter, reduced 20% with respect to the control.
      The histological analysis revealed epithelium disorganization in hepatopancreas
      tubules, confirming the existence of structural damage caused by
      hexachlorobenzene.

PMID- 16978757
TI  - Dynamic changes of heme oxygenase-1 and carbon monoxide production in acute liver
      injury induced by carbon tetrachloride in rats.
AB  - Heme oxygenase-1, a stress-responsive enzyme that catabolizes hemes into carbon
      monoxide, biliverdin, and iron, has been shown to play a pivotal role in many
      physiological and pathological situations. Here we investigated changes in HO-1
      enzyme activity and protein expression, and its end product carbon monoxide
      concentrations in the liver of rats after CCl(4) treatment. We found that CCl(4)
      administration not only induced severe liver damage in rats, as demonstrated by
      dramatic elevation of ALT, AST levels and severe histopathological changes, but
      also resulted in a prominent up-regulation of HO-1 enzyme activity. Western blot
      and immunohistochemical analysis confirmed that expression of HO-1 protein was
      also increased significantly in a time-dependent manner following CCl(4)
      treatment, and localized mainly in liver cells around the central vein. In
      addition, CO concentrations in the liver of CCl(4)-treated rats were elevated
      remarkably in the same time-dependent way as HO-1 induction in contrast to the
      control rats. These data indicated that HO-1/CO pathway was greatly up regulated
      in the liver of rats after CCl(4) treatment, which might play an important
      protective role in the pathophysiological mechanism underlying CCl(4)-induced
      hepatotoxicity. It therefore suggested that more relevant studies should be
      carried out in the future to clarify the detailed mechanisms.

PMID- 16978758
TI  - In vitro metabolism of tributyltin and triphenyltin by human cytochrome P-450
      isoforms.
AB  - The metabolic fate of tributyltin and triphenyltin may contribute to the toxicity
      of these chemicals. We used human hepatic cytochrome P-450 (CYP) systems to
      confirm the specific CYP(s) involved in the in vitro metabolism of tributyltin
      and triphenyltin. There were no significant sex differences in the metabolic
      pattern of tributyltin or triphenyltin, indicating that the CYP(s) responsible
      for the metabolism of these chemicals in humans is/are not sex-specific form(s).
      Six major drug-metabolizing isoforms of cDNA-expressed human CYPs and the CYP2C
      subfamily were tested to determine their metabolic capacities for tributyltin and
      triphenyltin. CYP2C9, 2C18, 2C19, and 3A4 significantly mediated both
      dealkylation and dearylation of these triorganotins. Furthermore, the metabolism
      of tributyltin and triphenyltin was significantly inhibited in vitro by
      pretreatment with selective inhibitors, azamulin for CYP3A4 and N-3
      benzylnirvanol for CYP2C19. Since the CYP2C18 content of hepatic microsomes in
      humans is relatively low, CYP2C9, 2C19, and 3A4 might be the main isoforms of CYP
      that are responsible for tributyltin and triphenyltin metabolism in the human
      liver.

PMID- 16978759
TI  - Pharmacokinetic modeling of saturable, renal resorption of perfluoroalkylacids in
      monkeys--probing the determinants of long plasma half-lives.
AB  - Perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) compounds
      associated with surface protection product manufactures are distributed globally.
      The 3-5-year half-lives, reproductive and liver toxicity in animals, and lack of
      understanding of the factors regulating retention in the body have led to a world
      wide public concern for use of these materials. Using a novel physiologically
      motivated pharmacokinetic model for renal clearance, perfluoroalkylacid
      pharmacokinetics in monkeys was successfully described by renal resorption via
      high efficiency transporters for both intravenous and oral dosing. Intravenous
      dosing with both PFOA and PFOS in Cynomolgus monkeys produced time course curves
      consistent with a two-compartment distribution. Extending the PK model for
      intravenous dosing to examine blood and urine time course data for repeated oral
      dosing clearly identified the saturable renal resorption. Resorption depends on
      kinetic factors for transport (T(mC), transport maximum; K(T), transport
      affinity) and free fraction in plasma (f(plasma)). For PFOA, these parameters
      were estimated to be 5mg/(h kg) (T(mC)), 0.055 mg/L (K(T)), and 0.02 (f(plasma)).
      PFOS has longer half-life and had respective values of 13.6 mg/(h kg), 0.023
      mg/L, and 0.025. PFOS appeared to have a higher transport capacity and lower
      affinity than PFOA. Human kinetics indicates even higher resorption efficiency.

PMID- 16978760
TI  - Deltamethrin-induced oxidative damage and biochemical alterations in rat and its
      attenuation by Vitamin E.
AB  - Deltamethrin is a synthetic pyrethroid insecticide used worldwide in agriculture,
      home pest control, protection of foodstuff and disease vector control. The
      objective of this study was to investigate the propensity of deltamethrin to
      induce oxidative stress and changes in biochemical parameters and enzyme
      activities in male rats following a short-term (30 days) oral exposure and its
      possible attenuation by Vitamin E (Vit. E). Rats were assigned to 1 of 4
      treatment groups: 0mg Vit. E and 0mg deltamethrin/kg body weight (BW) (control);
      100mg Vit. E/kg BW; 1.28mg deltamethrin/kg BW; 100mg Vit. E plus 1.28mg
      deltamethrin/kg BW. Results obtained showed that deltamethrin significantly
      (P<0.05) induced thiobarbituric acid-reactive substances (TBARS; the marker of
      lipid peroxidation) in plasma. The activities of glutathione S-transferase (GST)
      and superoxide dismutase (SOD) were significantly decreased due to deltamethrin
      administration. On the other hand, treatment with Vitamin E alone increased the
      activities of GST and SOD, and decreased the levels of TBARS. Also, Vitamin E
      alleviated the harmful effect of deltamethrin in the combination group. Enzymatic
      activities of aminotransferases (AST and ALT), phosphatases (AcP and AlP) and
      lactate dehydrogenase (LDH) in plasma were significantly increased, while
      acetylcholinesterase (AChE) was inhibited. Deltamethrin significantly (P<0.05)
      increased the levels of plasma total lipid (TL), cholesterol, triglyceride (TG),
      low density lipoprotein (LDL) and very low density lipoprotein (VLDL), while the
      level of high density lipoprotein (HDL) decreased. Vitamin E alone decreased the
      levels of lipids and lipoproteins, and alleviated the harmful effects of
      deltamethrin. Concentrations of glucose, urea, creatinine and total bilirubin
      were increased. While, plasma total protein (TP), albumin (A) and globulin (G)
      were significantly (P<0.05) decreased. The present study revealed that the
      presence of Vitamin E could diminish the adverse effects of deltamethrin on most
      of biochemical parameters, lipid peroxidation and enzyme activities in rats.

PMID- 16978761
TI  - Mutagenicity of cytochrome P450 2E1 substrates in the Ames test with the
      metabolic competent S. typhimurium strain YG7108pin3ERb5.
AB  - Poor metabolic competence of in vitro systems was proposed to be one of their
      major shortcomings accounting for false negative results in genotoxicity testing.
      For several "low molecular weight cancer suspects" this was specifically
      attributed to the lack of cytochrome P450 2E1 (CYP2E1) in conventional in vitro
      metabolising systems. One promising attempt to overcome this problem is the
      transfection of "methyltransferase-deficient"S. typhimurium strains with the
      plasmid pin3ERb5. This plasmid contains DNA encoding for a complete electron
      transport chain, comprising P450 reductase, cytochrome b5 and cytochrome P450
      2E1. In order to answer the question if CYP2E1 substrates that yield negative or
      inconclusive results in the Ames test can be activated by metabolic competent
      bacterial strains, we used YG7108pin3ERb5 to investigate the following compounds:
      acetamide, acrylamide, acrylonitrile, allyl chloride, ethyl acrylate, ethyl
      carbamate, methyl-methacrylate, vinyl acetate, N-nitrosopyrrolidine,
      trichloroethylene and tetrachloroethylene. N-Nitrosodiethylamine served as a
      positive control. In addition to these known or proposed CYP2E1 substrates, we
      investigated the polycyclic aromatic hydrocarbon benzo[alpha]pyrene and the
      heterocyclic aromatic amines 2-aminofluorene and 2-aminoanthracene. RESULTS: The
      extensive metabolic competence of the transformed strain is underlined by results
      showing strong mutagenicity between 10 and 500 micro g N-nitrosopyrrolidine per
      plate. Unexpectedly, 2-aminoanthracene was mutagenic at a concentration range
      between 25 and 250 micro g per plate using YG7108pin3ERb5. Moreover, we
      demonstrate for the first time a clear response of sufficiently characterised
      allyl chloride in the Ames test at a reasonably low concentration range between
      300 and 1500 micro g per plate. We achieved similar results in the parent strain
      YG7108 with conventional metabolic activation. Without metabolic activation less
      pronounced mutagenicity occurred, suggesting a contribution of a direct
      alkylating effect. Propylene oxide is usually contained in allyl chloride as
      stabilizer at amounts up to 0.09%. Though YG7108 revealed to be very sensitive
      towards propylene oxide, allyl chloride dissolved in water was not mutagenic,
      showing that no water soluble compounds contribute to its mutagenicity. None of
      the remaining compounds showed mutagenic effects using YG7108pin3ERb5.
      CONCLUSION: YG7108pin3ERb5 and its parent strain YG7108 are sensitive for
      compounds which are negative in conventional tester strains including N
      nitrosodiethylamine, N-nitrosopyrrolidine, propylene oxide and allyl chloride.

PMID- 16978762
TI  - Photophysics of ANS. I. Protein-ANS complexes: Intestinal fatty acid binding
      protein and single-trp mutants.
AB  - We continue investigations into the physical chemistry of intestinal fatty acid
      binding protein, I-FABP, and its interaction with ANS and other ligands [cf
      references [Kirk, W., E. Kurian, and F. Prendergast. 1996. Characterization of
      the sources of protein-ligand affinity: 1-sulfonato-8-anilinonaphthalene binding
      to intestinal fatty acid binding protein. Biophys. J. 70: 69-83., Kurian, E., W.
      Kirk, and F. Prendergast. 1996. Affinity of fatty acid for rRat intestinal fatty
      acid binding protein: Further examination. Biochemistry. 35:3865-74]. The
      photophysics of the wt protein is compared with that in two mutants which lack
      respectively one or the other of two trp moieties, one of which, trp 82, is
      located near the binding region for the polar head group of ligands. These
      studies afford a look into how the fluorescence of the wt protein is established,
      that is, as an almost direct sum of the fluorescence of the two individual trp
      residues, and how this fluorescence is quenched upon binding to ANS. Though we
      have access to all the relevant spectroscopic and geometric information necessary
      to specify in detail the Foerster-Dexter energy transfer model, the quenching
      process is not explicable in terms of very-weak coupling, as is usually assumed
      in fluorescence studies in protein systems, but in terms of a stronger effect
      which goes beyond the simple very-weak dipole:dipole formalism. The quenching of
      trp emission by bound ANS is not as great as that anticipated by ordinary
      resonance energy transfer, neither is the quenching observed in the reduced
      lifetimes of the trp emission upon ANS binding as great as that observed in
      steady-state intensity. However the observed steady-state quenching is explicable
      in terms derived from the lifetime measurements, together with observed spectral
      band shifts, by the exciton coupling model we invoke here.

PMID- 16978763
TI  - Mean-field coupling of calcium oscillations in a multicellular system of rat
      hepatocytes.
AB  - In a multicellular system of rat hepatocytes and even in an intact liver,
      cytoplasmic calcium oscillations are synchronized and highly coordinated. In this
      paper, the mean-field coupling term has been introduced to describe the coupling
      flux, which is more efficient than gap junctional coupling terms. An optimal
      coupling strength and an optimal stimulation level for the synchronization of the
      coupled system have been observed in this paper. Moreover, it has been proved
      that these results are independent of the cells number. Interestingly, it has
      been observed that the intracellular noise and the extracellular noise have
      different effects on the synchronization of the coupled system.

PMID- 16978764
TI  - Release of Zn, Ni, Cu, SO4(2-) and CrO4(2-) as a function of pH from cement-based
      stabilized/solidified refinery oily sludge and ash from incineration of oily
      sludge.
AB  - A framework for the evaluation of leaching behavior of inorganic constituents
      from stabilized/solidified refinery oily sludge and ash produced from
      incineration of oily sludge with cement was employed. Metal and anion release as
      a function of pH was investigated. The leaching test consisted of multiple
      parallel extractions at pH range from 2 to 12. Remarkably good immobilization
      >98% was observed for metals of solidified ash at pH>6 and >93% of solidified
      oily sludge at pH>7. Sulfate leaching was high at pH range 2-12. The leaching
      behavior of metals and anions was simulated by VMINTEQ. The calculations showed
      that leaching behavior of Zn, Ni and Cu was controlled by chemical equilibrium
      and surface complexation onto ferrihydrite, at the pH range 2-12. The dominant
      solid phases that controlled metal leachability were metal hydroxides. The
      dominant mechanism that described sulfate leaching was found to be chemical
      equilibrium. Sulfate and also chromate leachability was controlled by Ettringite
      and Cr(VI)Ettringite as the major minerals affecting their release.

PMID- 16978765
TI  - Coal-based bottom ash (CBBA) waste material as adsorbent for removal of textile
      dyestuffs from aqueous solution.
AB  - A locally available CBBA waste material was used as adsorbent for removal of
      reactive dyes from synthetic textile wastewater. This study presents the results
      of our investigation on color removal from synthetic wastewater containing
      Vertigo Blue 49 (CI Blue 49) and Orange DNA13 (CI Orange 13) by adsorption onto
      CBBA waste material. The effectiveness of CBBA waste material in adsorbing
      reactive dyes from aqueous solutions was studied as a function of contact time,
      initial dye concentration and pH by batch experiments. Leachability of waste
      material was also evaluated using standard leaching test with deionized water
      (DIN38414-S4). pH 7 was more favorable for color removal from both Vertigo Blue
      49 (CI Blue 49) and Orange DNA (CI Orange 13). Dyestuff adsorption capacities of
      CBBA for Vertigo Blue 49 and Orange DNA13 were 13.51 and 4.54mg dye/g adsorbent,
      respectively. The adsorption isotherms for the CBBA can be better described by
      the Freundlich isotherm. The results showed that the dyestuff uptake process for
      both dyes followed the second-order kinetics. The bottom ash used in this study
      is not classified as ecotoxic/hazardous material according to the French proposal
      for a criterion and evaluation methods of waste ecotoxicity (CEMWE) and the
      German regulation on Hazardous Waste Classification (HWC).

PMID- 16978766
TI  - Arsenic sorption onto natural hematite, magnetite, and goethite.
AB  - In this work the sorption of As(III) and As(V) on different natural iron oxides
      (hematite, magnetite, and goethite) has been studied as a function of different
      parameters. The sorption kinetics for the three iron oxides shows that
      equilibrium is reached in less than 2 days and the kinetics of sorption seems to
      be faster for goethite and magnetite than for hematite. The variation of the
      arsenic sorbed on the three different sorbents as a function of the equilibrium
      arsenic concentration in solution has been fitted with a non-competitive Langmuir
      isotherm. The main trend observed in the variation of the arsenic sorbed with pH
      is the decrease of the sorption on the three sorbents at alkaline pH values,
      which agrees with results found in the literature. Highest As(III) sorption was
      observed on hematite surface in all the pH range compared to goethite and
      magnetite. Natural minerals studied in this work had similar sorption capacities
      for arsenic than synthetic sorbents.

PMID- 16978767
TI  - The removal and recovery of Cr(VI) by Li/Al layered double hydroxide (LDH).
AB  - Hexavalent Cr has been identified as one of the toxic metals commonly present in
      industrial effluents. Among the treatment techniques developed for removing
      Cr(VI) from waste waters, sorption is most commonly applied, due to its
      simplicity and efficiency. However, few adsorbents can be recycled and reused
      cost-effectively. In this study, the removal and recovery of Cr(VI) from water
      using Li/Al LDH was investigated. The removal of Cr(VI) by Li/Al LDH was
      evaluated in a batch mode. The results demonstrated that Cr(VI) adsorption onto
      Li/Al LDH occurs by replacing the Cl(-) that originally exists in the interlayer
      of the adsorbent. The degree of Cr(VI) adsorption observed for Li/Al LDH was
      relatively high and the process occurred rapidly; however, a portion of adsorbed
      Cr(VI) was gradually desorbed, due to the Li de-intercalation of Li/Al LDH.
      Lithium de-intercalation from Li/Al LDH with interlayer Cl(-) and interlayer
      Cr(VI) follows the first order kinetics and has the activation energies of 76.6
      and 41.5 kJ mol(-1), respectively. The properties of thermal unstability and the
      high adsorption capacity of Li/Al LDH may lead to the development of an
      innovative technique for the removal of Cr(VI) from Cr(VI)-containing wastewater.
      That is, Li/Al LDH may be used as an effective adsorbent for the adsorption of
      Cr(VI) in an ambient environment. Following the adsorptive process, the adsorbed
      Cr(VI) may be released, using heated water to treat the Cr(VI)-containing Li/Al
      LDH particles. Through this hydrothermal treatment of the used adsorbent, Cr(VI)
      can be recovered and the solid product (gibbsite) can be recycled for further
      use.

PMID- 16978768
TI  - Dye removal by low cost adsorbents: hazelnut shells in comparison with wood
      sawdust.
AB  - Batch adsorption of Methylene Blue, up to 1000 mg L(-1), and Acid Blue 25, up to
      500 mg L(-1), onto ground hazelnut shells was studied in comparison with sawdust
      of various species of wood, in order to explore the potential use of this
      material as low cost adsorbent for dye removal in dyehouse effluents. The
      adsorption kinetics was investigated according to Lagergren's model, but the best
      fit was achieved by a second order equation. The equilibrium data were processed
      according to Langmuir's model and higher adsorption capacity values towards both
      dyes were shown by hazelnut shells than wood sawdust. Moreover, fixed bed
      adsorption of Methylene Blue was performed on hazelnut shell columns and the
      breakthrough curves were determined by varying bed depth, flow rate and influent
      concentration. The data were processed according to Bohart-Adams model and the
      column performances could be predicted by the bed depth service time (BDST)
      approach.

PMID- 16978769
TI  - Leachate pretreatment for enhancing organic matter conversion in landfill
      bioreactor.
AB  - Direct recycling of leachate from refuse of high food waste content was shown to
      ineffectively stabilize the refuse. This work aims at evaluating the effects of
      three pretreatments of leachate on the refuse stabilization efficiency were
      investigated. Pretreatment of leachate using an anaerobic upflow filtration
      bioreactor (UFB) or a well-decomposed waste layer could reduce the COD and
      provide methanogens, both were beneficial to establish early methanogenesis
      status. Using an aerobic sequential batch reactor (SBR) to pretreat the leachate
      could reduce its COD to 1000 mg l(-1), but the fully developed methanogenesis
      phase would be built up in a later stage. The organic matters in the effluent
      leachate inhibited both the hydrolysis/acidogenesis and the methanogenesis steps
      in the refuse. With the dilution and acid neutralization effects by the recycled
      leachate, a favorable methanogenetic environment could be produced from the
      column's top, which moved downward along, and finally made the breakthrough of
      the column.

PMID- 16978770
TI  - A new high-nitrogen compound [Mn(ATZ)(H2O)4] x 2H2O: synthesis and
      characterization.
AB  - A new high-nitrogen compound [Mn(ATZ)(H(2)O)(4)] x 2H(2)O (ATZ=5,5
      azotetrazolate) was synthesized. Crystal structure and elemental, IR and thermal
      analyses were investigated in the present work. It crystallized in triclinic
      space group P-1 with lattice parameters a=6.304(2)A, b=7.004(2)A, c=7.921(3)A,
      alpha=76.114(5) degrees , beta=74.023(5) degrees , gamma=69.254(4) degrees . TG
      DTG and DSC measurements are employed to postulate the thermal decomposition
      mechanism. The thermal decomposition kinetics of the main exothermic reaction was
      investigated by non-isothermal method and obtained its enthalpy of decomposition
      and the probable kinetic mechanism. An attempt was made to incorporate the
      relation between thermal stability and the structure.

PMID- 16978771
TI  - Adsorption of Cr(VI) from synthetic solutions and electroplating wastewaters on
      amorphous aluminium oxide.
AB  - The adsorption behaviour of amorphous aluminium oxide was studied with respect to
      Cr(VI) in order to consider its application to purify electroplating wastewaters.
      A batch method was employed using Cr(VI) concentrations ranged from 10 to
      200mg/l. The Langmuir model was found to describe the adsorption process well,
      offering a maximum adsorption capacity of 78.1mg/g. The effect of ionic strength
      (0-0.1M KNO(3)), pH (3-9) and competitive solutes (molar ratio [Cr(VI)]/[SO(4)(2
      )]=1 and 100) on the retention process was evaluated. Cr(VI) adsorption on
      amorphous aluminium oxide appeared to be dependent on ionic strength with a more
      pronounced effect in acid conditions. Conversely, adsorption was not affected by
      pH in acid medium, but decreased when pH sifted to alkaline values. The presence
      of SO(4)(2-) greatly reduced Cr(VI) removal across the entire pH range when both
      solutes were present in similar concentrations. Amorphous aluminium oxide also
      showed a high adsorption capacity when used in the purification of Cr(VI)
      electroplating wastewaters. The adsorbent doses required to attain more than 90%
      of Cr(VI) removal varied between 1 and 5 g/l depending on Cr(VI) concentration in
      wastewaters.

PMID- 16978772
TI  - Emission characteristics of coal combustion in different O2/N2, O2/CO2 and O2/RFG
      atmosphere.
AB  - This study investigates the emission characteristics of CO(2), SO(2) and NOx in
      the flue gas of coal combustion by varying the compositions and concentrations of
      feed gas (O(2)/CO(2)/N(2)) and the ratios of recycled flue gas. The differences
      between O(2)/recycled flue gas (O(2)/RFG) combustion and general air combustion
      are also discussed. Experimental results indicate that the maximum concentration
      of CO(2) in O(2)/CO(2) combustion system is 95% as the feed gas is 30% O(2)/70%
      CO(2). The average concentration of CO(2) in the flue gas of O(2)/CO(2) coal
      combustion system is higher than 90% and much higher than that of O(2)/N(2) coal
      combustion system. This high concentration of CO(2) is beneficial for the
      separation of CO(2) from the flue gas by adsorption or absorption technologies.
      The maximum concentration of CO(2) in O(2)/N(2) combustion system is only 34% at
      the feed gas 50% O(2)/50% N(2), the concentration of CO(2) is increased with the
      concentration of O(2) in feed gas. By O(2)/CO(2) combustion technology, higher
      concentration of SO(2) is produced as the feed gas is 30% O(2)/70% CO(2) or 40%
      O(2)/60% CO(2), while higher concentration of NOx is produced as the feed gas is
      20% O(2)/80% CO(2) or 50% O(2)/50% CO(2). The mass flow rates of CO(2), SO(2) and
      NOx in the flue gas are all increased with the ratio of recycled flue gas except
      for the feed gas 20% O(2)/80% CO(2). The enhanced mass flow rates of air
      pollutants in such O(2)/RFG combustion system are also beneficial for improving
      the control efficiencies of air pollution control devices. By O(2)/N(2)
      combustion technology, higher concentrations of SO(2) and NOx are produced as the
      feed gas is 21% O(2)/79% N(2). The results also indicate that the formation of
      NOx in general air combustion system is higher than that in O(2)/RFG or
      O(2)/CO(2) combustion system.

PMID- 16978773
TI  - Inactivation of Chironomid larvae with chlorine dioxide.
AB  - In this paper, comparative experiments on the inactivation of Chironomid larvae
      by chlorine dioxide and chlorine were conducted. In addition, batch experiments
      were performed in order to analyze the influence of pH value, organic precursor
      concentration and temperature on the inactivation efficiency of Chironomid larvae
      with chlorine dioxide. Based on it, removal effect of different pre-oxidation
      followed by coagulation process on Chironomid larvae in raw water was evaluated.
      The results showed that chlorine dioxide possessed better inactivation
      performance than chlorine, and complete inactivation of Chironomid larvae was
      obtained at CT value of 37.5 mg min/L (dose of 1.5mg/L and exposure time of 25
      min). The pH in the range of 6-8 did not affect the inactivation efficiency of
      chlorine dioxide, whereas pH 10 resulted in around 10% decrease in inactivation
      rate. Meanwhile, the organic precursor had negative effects on inactivation,
      indicated by the decreased inactivation rate from 100% at TOC concentration of
      0mg/L to 62.2% at 8 mg/L when the CT value was 45 mg min/L. With regard to the
      temperature, the inactivation efficiency of Chironomid larvae was significantly
      improved with the temperature increasing within the range investigated of 10-25
      degrees C. The inactivation rate was reduced by 68.9% when temperature reduced
      from 25 degrees C to 10 degrees C. The coagulation jar test showed that
      Chironomid larvae in the raw water could be completely removed by chlorine
      dioxide pre-oxidation in combination with the coagulation process at CT value of
      24.8 mg min/L.

PMID- 16978774
TI  - Air flow paths and porosity/permeability change in a saturated zone during in
      situ air sparging.
AB  - This study develops methods to estimate the change in soil characteristics and
      associated air flow paths in a saturated zone during in situ air sparging. These
      objectives were achieved by performing combined in situ air sparging and tracer
      testing, and comparing the breakthrough curves obtained from the tracer gas with
      those obtained by a numerical simulation model that incorporates a predicted
      change in porosity that is proportional to the air saturation. The results reveal
      that revising the porosity and permeability according to the distribution of gas
      saturation is helpful in breakthrough curve fitting, however, these changes are
      unable to account for the effects of preferential air flow paths, especially in
      the zone closest to the points of air injection. It is not known the extent to
      which these preferential air flow paths were already present versus created,
      increased, or reduced as a result of the air sparging experiment. The transport
      of particles from around the sparging well could account for the overall increase
      in porosity and permeability observed in the study. Collection of soil particles
      in a monitoring well within 2m of the sparging well provided further evidence of
      the transport of particles. Transport of particles from near the sparging well
      also appeared to decrease the radius of influence (ROI). Methods for predicting
      the effects of pressurized air injection and water flow on the creation or
      modification of preferential air flow paths are still needed to provide a full
      description of the change in soil conditions that accompany air sparging.

PMID- 16978775
TI  - Lower levels of cerebrospinal fluid amyloid beta (Abeta) in non-demented Indian
      controls.
AB  - Prevalence of Alzheimer's disease in Indian population is lower than in developed
      countries. To determine whether limitation of amyloid beta (Abeta) concentration
      may be responsible for lower rate of incidence, we measured the levels of Abeta
      in cerebrospinal fluid (CSF) collected from 72 non-demented individuals ranging
      in the age from 20 years to 65 years. These samples were segregated into three
      groups ranging from 20-35 years, 36-50 years and 51-65 years of age. Levels of
      Abeta could be detected in all the age groups and they were much lower than the
      values reported in literature from the developed countries. No significant
      difference in the average level of Ass was observed with increase in age.

PMID- 16978776
TI  - RhoA protein expression correlates positively with degree of malignancy in
      astrocytomas.
AB  - Astrocytic tumors are the most common intracranial neoplasms. Their prognoses
      correlate with a conventional morphological grading system that suffers from
      diagnostic subjectivity and hence, inter-observer inconsistency. A molecular
      marker that provides an objective reference for classification and
      prognostication of astrocytic tumors would be useful in diagnostic pathology.
      RhoA, a GTPase protein involved in cell migration and adhesion, has been shown to
      be upregulated in a variety of human cancers. Based on direct analysis of
      clinical materials, our study demonstrates increased expression of RhoA in high
      grade astrocytomas. This observation may be relevant to astrocytoma biology and
      the development of potential therapeutics against high-grade astrocytomas. Of
      more immediate consequence, utilization of this marker may aid in the routine
      pathological grading (and hence prognostication) of astrocytomas.

PMID- 16978777
TI  - Stimulation of neurite outgrowth on neonatal cerebral astrocytes is enhanced in
      the presence of BDNF.
AB  - An area of increasing interest in spinal cord injury (SCI) research is the
      development of multi-factorial strategies to promote repair. In this respect, a
      prominent role is played by cell transplantation, the reparative effect of which
      can be enhanced by additional use of neurotrophic factors. Immature astrocytes
      have shown their merit in stimulating axon regeneration upon transplantation into
      the injured spinal cord. Brain-derived neurotrophic factor (BDNF) influences a
      wide range of descending axon tracts in the injured spinal cord. In the present
      study, we hypothesized that the neurite outgrowth of neonatal cortical neurons on
      immature astrocytes is enhanced in the presence of BDNF. To test this hypothesis,
      neonatal cortical neurons were cultured on neonatal astrocytes for 2 days in
      absence or presence of BDNF. The length of the longest neurite and the number of
      primary neurites per neuron were taken as measures to study neurite outgrowth. We
      show that BDNF dose-dependently enhanced neurite outgrowth of neonatal cerebral
      cortical neurons grown on immature astrocytes. Compared to conditions without
      BDNF, the length of the longest neurite increased by 25.5 and 28.8% in presence
      of 10 and 100 pg/ml BDNF, respectively. BDNF did not alter the density of the
      immature astrocytes. We conclude that the presence of BDNF enhances the neurite
      outgrowth on immature astrocytes. A multi-factorial strategy based on
      transplantation of neonatal astrocytes in the presence of additional BDNF is
      recommended and may stimulate axon regrowth after experimental injury to the
      central nervous system.

PMID- 16978778
TI  - Development- and activity-dependent regulation of SNAP-25 phosphorylation in rat
      brain.
AB  - Synaptosomal-associated protein of 25kDa (SNAP-25), a member of the SNARE
      proteins essential for neurotransmitter release, is phosphorylated at Ser(187) in
      PC12 cells and in the rat brain in a protein kinase C-dependent manner. It
      remains unclear how the phosphorylation of SNAP-25 is regulated during
      development and by neuronal activity. We studied the mode of SNAP-25
      phosphorylation at Ser(187) in the rat brain using an anti-phosphorylated SNAP-25
      antibody. Both the expression and phosphorylation of SNAP-25 increased remarkably
      during the early postnatal period, but their onsets were quite different. SNAP-25
      expression was detected as early as embryonic Day 18, whereas the phosphorylation
      of SNAP-25 could not be detected until postnatal Day 4. A delay in the onset of
      phosphorylation was also observed in cultured rat hippocampal neurons. The
      phosphorylation of SNAP-25 was regulated in a neuronal activity-dependent manner
      and, in the rat hippocampus, decreased by introducing seizures with kainic acid.
      These results clearly indicated that the phosphorylation of SNAP-25 at Ser(187)
      is regulated in development- and neuronal activity-dependent manners, and is
      likely to play important roles in higher brain functions.

PMID- 16978779
TI  - Carbamazepine interacts with a slow inactivation state of NaV1.8-like sodium
      channels.
AB  - Carbamazepine was tested on high-threshold TTX-resistant Na+ currents (TTX-R
      currents), evoked from acutely isolated rat dorsal root ganglion (DRG) cells.
      Under control conditions, the TTX-R-currents recorded from different DRG cells
      varied greatly regarding use-dependent inactivation (TTX-R-current UDI), measured
      as the percent decrease in current amplitude induced by changing the current
      activation rate from 0.1 Hz to 1.0 Hz. Also, when TTX-R-currents were evoked at
      0.1 Hz from a holding potential (hp) of -60 mV, a larger fraction of TTX-R
      channels resided tonically in a slow inactivation state in DRG cells with more
      TTX-R-current UDI versus those with less TTX-R-current UDI. The block of TTX-R
      currents evoked from hp -60 mV by 100-microM carbamazepine and the EC50 for
      carbamazepine block was positively correlated with TTX-R-current UDI. The slope
      factors estimated for the concentration-response curves averaged 0.68, suggesting
      the presence of low and high affinity sites. Fitting the data with a two-site
      binding isotherm gave estimates of 30 microM and 760 microM for the EC50s of the
      high and low affinity sites, respectively. The fraction of the total fit
      attributed to the high affinity site was positively correlated with TTX-R-current
      UDI. Carbamazepine increased the fast and slow time constants for recovery from
      inactivation and the fraction of the fit attributed to the slow time constant.
      These data suggest that carbamazepine interacts with a slow inactivation state of
      TTX-R-channels. This particular mechanism might be exploited in future research
      aimed at developing pain medications that selectively block Na(V)1.8 channels or
      Na+ channels in general.

PMID- 16978780
TI  - mRNA and protein expression and activities of nitric oxide synthases in the
      lumbar spinal cord of neonatal rats after sciatic nerve transection and melatonin
      administration.
AB  - Sciatic axotomy in 2-day-old rats (P2) causes lumbar motoneuron loss, which could
      be associated with nitric oxide (NO) production. NO may be produced by three
      isoforms of synthase (NOS): neuronal (nNOS), endothelial (eNOS) and inducible
      (iNOS). We investigated NOS expression and NO synthesis in the lumbar enlargement
      of rats after sciatic nerve transection at P2 and treatment with the antioxidant
      melatonin (sc; 1 mg/kg). At time points ranging from P2 to P7, expression of each
      isoform was assessed by RT-PCR and immunohistochemistry; catalytic rates of
      calcium-dependent (nNOS, eNOS) and independent (iNOS) NOS were measured by the
      conversion of [3H]L-arginine to [3H]L-citrulline. All NOS isoforms were expressed
      and active in unlesioned animals. nNOS and iNOS were detected in some small cells
      in the parenchyma. Only endothelial cells were positive for eNOS. No NOS isoform
      was detected in motoneurons. Axotomy did not change these immunohistochemical
      findings, nNOS and iNOS mRNA expression and calcium-independent activity at all
      survival times. However, sciatic nerve transection reduced eNOS mRNA levels at P7
      and increased calcium-dependent activity at 1 and 6 h. Melatonin did not alter
      NOS expression. Despite having no action on NOS activity in unlesioned controls
      the neurohormone enhanced calcium-dependent activity at 1 and 72 h and reduced
      calcium-independent catalysis at 72 h in lesioned rats. These results suggest
      that NOS isoforms are constitutive in the neonatal lumbar enlargement and are not
      overexpressed after sciatic axotomy. Changes in NO synthesis induced by axotomy
      and melatonin administration in the current model are discussed considering some
      beneficial and deleterious effects that NO may have.

PMID- 16978781
TI  - Relationship between diffusion tensor imaging and brain morphology in patients
      with myotonic dystrophy.
AB  - Myotonic dystrophy type 1 (MyD) is a common inherited neuromuscular disorder. In
      addition to neuromuscular symptoms, many MyD patients show central nervous system
      neuropathology. This study evaluated whether MyD patients display diffusion
      tensor (DT) abnormalities associated with regional cortical atrophy and clinical
      features. Three-dimensional T1-weighted and DT magnetic resonance images of the
      brain were obtained in 11 MyD patients and 13 age- and sex-matched healthy
      subjects. Fractional anisotropy (FA) and mean diffusivity (MD) values were
      calculated in corpus callosum subregions with DT imaging (DTI) along with
      volumetric changes, and correlations with clinical features were examined.
      Differences between MyD patients and healthy subjects were analyzed
      statistically. Significantly lower FA and higher MD values were found in the
      genu, rostral body, anterior midbody, posterior midbody and splenium in MyD
      patients than in control subjects (p<0.05, corrected; lower FA in the splenium
      was at a trend level). These corpus callosum subregions were the areas connected
      to cortical areas where significantly lower volumes were found in MyD patients.
      No significant decrease in volumes was noted in the parietal cortex, where
      connecting fibers pass through the isthmus in which DTI abnormalities were not
      detected in MyD patients. Significant negative correlations to volumes of frontal
      areas were noted, particularly bilateral motor areas, with cytosine thymine
      guanidine (CTG) triplet expansion. DTI results in corpus callosum may reflect
      morphological changes in the connecting cortical areas of MyD patients.

PMID- 16978782
TI  - Role of PKA and PKC in histamine H1 receptor-mediated activation of catecholamine
      neurotransmitter synthesis.
AB  - Activation of the histamine H1 receptor stimulates tyrosine hydroxylase (TH) to
      increase catecholamine neurotransmitter synthesis in mammalian brain and adrenal
      tissues. Histamine non-selectively activates both H1-linked phospholipase (PL)
      C/inositol phosphates (IP)/diacylglycerol (DAG) signaling and adenylyl cyclase
      (AC)/adenosine 3',5'-cyclic monophosphate (cAMP) signaling, confounding
      determination of signaling events involved in H(1)-mediated TH activation. This
      research uses two new functionally-selective H1 agonists, cis-PAB and trans-PAT,
      that selectively activate H1/PLC/IP/DAG and H1/AC/cAMP signaling, respectively,
      to characterize H(1)-mediated activation of TH in rat striatum and bovine adrenal
      chromaffin (BAC) cells. Histamine, cis-PAB, and trans-PAT produced a two-fold
      maximal TH activation by an H1 receptor mechanism in rat striatum and BAC cells.
      Histamine is more potent and efficacious in BAC cells (EC50 approximately 0.2
      microM, Emax approximately 200% basal) versus rat striatum (EC50 approximately
      0.4 microM; Emax approximately 150%). Cis-PAB and trans-PAT are more potent in
      rat striatum (EC50 approximately 0.1 microM for both agonists) versus BAC cells
      (EC50 approximately 1.0 microM for both), with similar efficacy in both
      preparations (Emax approximately 160% for both agonists). Signaling studies in
      BAC cells revealed that protein kinase (PK) A but not PKC is involved in H1 
      mediated TH activation by trans-PAT and histamine, while, both PKA and PKC are
      involved for cis-PAB. Results for cis-PAB suggest H1/PLC/IP/DAG/PKC signaling
      activates PKA, downstream of cAMP formation, indicating apparent direct
      activation of PKA by PKC.

PMID- 16978783
TI  - Novel Na+ -independent and adenine-specific transport system for adenine in
      primary cultured rat cortical neurons.
AB  - Endogenous adenine is an important modulator of cell survival and activity in the
      central nervous system. In the present study, we examined the transport
      mechanisms for adenine in primary cultured rat cortical neurons and astrocytes.
      [3H]Adenine was time-dependently taken up into neurons, but not into astrocytes.
      In kinetic analysis, the [3H]adenine uptake by neurons was observed to be
      saturable, and an Eadie-Hofstee plot showed that a single component was involved
      in the uptake, with kinetic parameters of Km=6.09 microM and Vmax=0.340 nmol/mg
      protein per min. In inhibition assaying by nucleobases and nucleosides, and
      inhibitors for equilibrative nucleoside transporters, organic ion transporters
      and peptide transporters, which were reported to transport nucleobases and their
      analogues, the [3H]adenine uptake by neurons was found to be significantly
      inhibited by excess concentrations of adenine, hypoxanthine and adenosine, and
      was greatly reduced only by the addition of adenine. Therefore, it was indicated
      that adenine in the extracellular fluid in the central nervous system is taken up
      into neurons, but not into astrocytes, and that neurons may present a novel Na+ 
      independent and adenine-specific transport system.

PMID- 16978784
TI  - Suppressive effect of simvastatin on interferon-beta-induced expression of CC
      chemokine ligand 5 in microglia.
AB  - Despite the pivotal role of microglia in immune system of the brain, a growing
      body of evidence suggests that the excessive microglial activation provokes
      neuronal and glial damages, leading to neurodegenerative and neuroinflammatory
      disorders. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or
      statins, have recently received much attention for their suppressive effects on
      inflammation in the central nervous system. In the current study, we have
      examined the statin-mediated inhibition of microglial function, especially that
      of chemokine production. Stimulation of microglial cells with interferon-beta
      (IFN-beta) resulted in the expression of CC chemokine ligand 5 (CCL5), a major
      chemoattractant of inflammatory cells. Microglial CCL5 response was
      synergistically potentiated by costimulation with IFN-beta and tumor necrosis
      factor-alpha (TNF-alpha). The simvastatin treatment significantly diminished the
      microglial CCL5 expression induced by IFN-beta alone or by IFN-beta/TNF-alpha
      combination. In the presence of simvastatin, the IFN-beta-induced activation of
      Janus kinase (Jak)-signal transducer and activator of transcription (STAT)
      pathway was attenuated, although this compound had little or no effect on the TNF
      alpha-evoked activation of nuclear factor kappaB and c-Jun N-terminal kinase
      pathways. In addition, chemical inhibitor of Jak-STAT signaling significantly
      diminished the IFN-beta-induced expression of CCL5 in microglia. Taken together,
      these results suggest that simvastatin suppresses the IFN-beta-induced expression
      of CCL5 via down-regulation of Jak-STAT signaling pathway.

PMID- 16978785
TI  - Vitellogenesis in the tick Amblyomma triste (Koch, 1844) (Acari: Ixodidae) Role
      for pedicel cells.
AB  - This study presents new information on the vitellogenesis of the tick Amblyomma
      triste. In this species, the ovary consists of a layer of epithelial cells, which
      form the ovarian wall, oogonia and developing oocytes; and the pedicel, a
      cellular structure that synthesizes and provides yolk precursors for developing
      oocytes. The pedicel also attaches oocytes to the external surface of the
      epithelial wall. In this study, evidence is provided in support of pedicel cells
      in providing compounds for oocytes during vitellogenesis.

PMID- 16978786
TI  - Effects of cattle treatment with a fluazuron pour-on on survival and reproduction
      of the dung beetle species Onthophagus gazella (Fabricius).
AB  - While resistance against many other classes of acaricides has been described,
      products containing benzoylphenyl urea are currently still successfully used
      against the pesticide-resistant blue tick (Boophilus decoloratus) in South
      Africa. In order to assess any adverse impact of these tickicides on the
      important dung beetle (Coleoptera: Scarabaeidae) fauna, a bioassay was undertaken
      on the ecotoxicological effects of a fluazuron (benzoylphenyl urea) pour-on
      formulation (Acatak) on the survival and reproduction of the African dung beetles
      species Onthophagus gazella (Fabricius). The experiment yielded no significant
      differences in adult or larval survival, egg production, fecundity and fertility
      between the control and treatment group following three beetle generations over.
      These results suggested that treatment of cattle with the fluazuron pour-on
      formulation Acatak was not detrimental to the selected dung beetle species in any
      notable way.

PMID- 16978787
TI  - Cytochrome P450 systems--biological variations of electron transport chains.
AB  - Cytochromes P450 (P450) are hemoproteins encoded by a superfamily of genes nearly
      ubiquitously distributed in different organisms from all biological kingdoms. The
      reactions carried out by P450s are extremely diverse and contribute to the
      biotransformation of drugs, the bioconversion of xenobiotics, the bioactivation
      of chemical carcinogens, the biosynthesis of physiologically important compounds
      such as steroids, fatty acids, eicosanoids, fat-soluble vitamins and bile acids,
      the conversion of alkanes, terpenes and aromatic compounds as well as the
      degradation of herbicides and insecticides. Cytochromes P450 belong to the group
      of external monooxygenases and thus receive the necessary electrons for oxygen
      cleavage and substrate hydroxylation from different redox partners. The classical
      as well as the recently discovered P450 redox systems are compiled in this paper
      and classified according to their composition.

PMID- 16978788
TI  - Tandem copies of a human rotavirus VP8 epitope can induce specific neutralizing
      antibodies in BALB/c mice.
AB  - The VP8 subunit protein of human rotavirus (HRV) plays an important role in viral
      infectivity and neutralization. Recombinant peptide antigens displaying the amino
      acid sequence M(1)ASLIYRQLL(10), a linear neutralization epitope on the VP8
      protein, were constructed and examined for their ability to generate anti-peptide
      antibodies and HRV-neutralizing antibodies in BALB/c mice. Peptide antigen
      constructs were expressed in E. coli as fusion proteins with thioredoxin and a
      universal tetanus toxin T-cell epitope (P2), in order to enhance the anti-peptide
      immune response. The peptide antigen containing three tandem copies of the VP8
      epitope induced significantly higher levels of anti-peptide antibody than only a
      single copy of the epitope, or the peptide co-administered with the carrier
      protein and T-cell epitope. Furthermore, the peptide antigen containing three
      copies of the peptide produced significantly higher virus-neutralization titres,
      higher than VP8, indicating that a peptide antigen displaying repeating copies of
      the amino acid region 1-10 of VP8 is a more potent inducer of HRV-neutralizing
      antibodies than VP8 alone, and may be useful for the production of specific
      neutralizing antibodies for passive immunotherapy of HRV infection.

PMID- 16978789
TI  - Adjuvant trials: Aromatase inhibitors in early breast cancer--are they alike?
AB  - Tamoxifen has been a standard therapy for breast cancer, but its use is
      complicated by serious events, including endometrial cancer and thromboembolism.
      Tamoxifen therapy beyond the recommended 5 years fails to improve disease
      outcomes, leaving many patients without a treatment option and susceptible to
      relapse. While all third-generation aromatase inhibitors have proven to be more
      effective than tamoxifen in reducing recurrence risk, in a variety of settings,
      there may be some differences in efficacy. For example, there is evidence that
      letrozole is the most potent suppressor of estrogen levels, and this may
      translate to greater clinical efficacy. Indeed, letrozole has been consistent at
      improving outcomes and is approved in a range of treatment settings, including
      extended adjuvant therapy, where tamoxifen is not indicated, and more recently,
      in the early adjuvant setting in the United States and Europe. While other
      potential long-term complications of aromatase inhibitor therapy will require
      further study, bone loss appears manageable through bisphosphonate therapy.
      Results of trials currently under way should determine the optimal use of the
      aromatase inhibitors in breast cancer therapy.

PMID- 16978790
TI  - Endogenous insulin signaling protects cultured neurons from oxygen-glucose
      deprivation-induced cell death.
AB  - Curiosity surrounding the physiological relevance of neural insulin signaling has
      gradually developed since the discovery that nervous tissue contains both the
      hormone and its receptor. Similar to other receptor tyrosine kinases, ligand
      interaction with the insulin receptor (IR) activates a variety of intracellular
      signaling pathways, particularly those relevant to cellular survival.
      Consequently, one explanation for the presence of the insulin pathway in the
      brain may involve participation in the response to neuronal injury. To
      investigate this possibility, the present study began by examining the effect of
      oxygen-glucose deprivation (OGD), a well-characterized in vitro model of
      ischemia, on ligand-binding, surface expression, and function of the IR in
      cultured rat neurons that were prepared under serum-free conditions. Reduced
      insulin-binding was observed following OGD, although surface expression of the
      receptor was not altered. However, OGD did significantly decrease the ability of
      insulin to stimulate phosphorylation of the transmembrane IR beta-subunit,
      without affecting protein expression of this subunit. Subsequent experiments
      focused on the manner in which pharmacologically manipulating IR function
      affected neuronal viability after OGD. Application of the IR sensitizer metformin
      moderately improved neuronal viability, while the specific IR tyrosine kinase
      inhibitor tyrphostin A47 was able to dramatically decrease viability; both
      compounds acted without affecting IR surface expression. Our study suggests that
      not only does the IR appear to play an important role in neuronal survival, but
      also that neurons may actively maintain IRs on the cell surface to compensate for
      the OGD-induced decrease in the ability of insulin to phosphorylate its receptor.

PMID- 16978792
TI  - Effect of spinal cord stimulation in an animal model of neuropathic pain relates
      to degree of tactile "allodynia".
AB  - Spinal cord stimulation (SCS) is an established treatment for chronic neuropathic
      pain. However, in recent studies conflicting results regarding the effect of SCS
      were noted in a selected group of patients suffering from complex regional pain
      syndrome and mechanical allodynia. In the present study we investigated the pain
      relieving effect of SCS in a rat experimental model of neuropathic pain as
      related to the severity of mechanical allodynia. Adult male rats (n=45) were
      submitted to a unilateral sciatic nerve ligation. The level of allodynia was
      tested using the withdrawal response to tactile stimuli with the von Frey test. A
      portion of these rats developed marked tactile hypersensitivity in the nerve
      lesioned paw (von Frey test), similar to "tactile allodynia" observed after nerve
      injury in humans. Prior to SCS treatment the rats were subdivided into three
      groups based on the level of allodynia: mild, moderate and severe. All allodynic
      rats were treated with SCS (n=27) for 30 min (f=50 Hz; pulse width 0.2 ms and
      stimulation at 2/3 of motor threshold) at 16 days post-injury. Our data
      demonstrate a differential effect of SCS related to the severity of the
      mechanical allodynia. SCS leads to a faster and better pain relief in mildly
      allodynic rats as compared with the more severely allodynic rats. Thus, we
      suggest that the selection and subdivision of patient groups similar to those
      defined in our experimental setting (mild, moderate and severe allodynic) may
      provide better pre-treatment prediction of possible therapeutic benefits of SCS.

PMID- 16978791
TI  - Augmentation of excitability in the hippocampus of juvenile rat.
AB  - The short-term plasticity of synaptic transmission has usually been related to
      neurotransmitter release-dependent processes. In this work, we describe a calcium
      and release-independent augmentation of the fiber volley (FVA) that appears
      during stimulation of the Wistar rat commissural/Schaffer collateral afferents at
      10-Hz. Among the possible mechanisms involved in this phenomenon, an increment in
      sodium channel density or the facilitation of recovery from inactivation does not
      seem to be responsible for this effect since the depolarization rate of the
      somatic action potentials (APs) of CA3 pyramidal cells decreases during the 10-Hz
      stimulation. On the other hand, an increase in the synchronization of the APs can
      be observed during the very first pulses of the 10-Hz tetanus. However, the major
      part of the FVA occurs with any increase in synchronization of AP firing.
      Finally, a strong increase in the firing probability, with kinetics similar to
      that observed with the FVA, appears at 10-Hz stimulation when APs are induced at
      threshold intensities. This hyperexcitability seems to be mediated by a residual
      depolarization that persists for more than 100 ms after the AP. The nature of
      this post-spike depolarization is uncertain since it persists in the absence of
      extracellular calcium and was not blocked by the application of phenytoin (100
      microM), and this excludes the implication of either calcium or sodium-persistent
      currents. Additionally, the increase of the stimulation strength did not alter
      this depolarization, which suggests that the presumed extracellular potassium
      accumulation produced after the synchronic stimulation of APs is not involved in
      the depolarization. Interestingly, the slow post-depolarization induced by both
      supra- and subthreshold pulses is well fitted by a single exponential decay with
      similar time constants, an indication that the tail depolarization may represent
      passive discharge of the membrane following an incomplete repolarization of the
      AP.

PMID- 16978793
TI  - Smoking-associated factors in myocardial infarction and unstable angina: do
      gender differences exist?
AB  - The aim of this study was to investigate demographic and psychological
      characteristics associated with smoking in patients with acute coronary syndrome
      (myocardial infarction or unstable angina). Interviews were conducted with 348
      consecutive hospitalized patients with acute coronary syndrome and included
      questions about demographic characteristics, coffee consumption, heart disease
      risk perception, economic status, alcohol consumption, depression, anxiety, and
      stress. Female group multivariate analysis showed that smoking in females was
      significantly and negatively associated with age, heart disease risk perception,
      and positively associated with coffee consumption. Male group multivariate
      analysis showed that for males, smoking was significantly and negatively
      associated with age, heart disease risk perception, and positively associated
      with coffee and alcohol consumption. Unlike studies conducted with non-heart
      disease patients, our results do not show an association between smoking and
      depression. Compared with nonsmokers, smokers with acute coronary syndrome are
      younger, more likely to drink coffee, and less likely to perceive smoking as a
      heart disease risk. Male smokers are also more likely to drink alcohol,
      indicating that they use more psycho-stimulants than do nonsmoking men and women
      who smoke.

PMID- 16978794
TI  - Major depressive disorder viewed as a dysfunction in astroglial bioenergetics.
AB  - For many years scientists and physicians have pondered upon the apparent
      connection between depressive disorder and diabetes mellitus. Several
      epidemiologic studies confirm that diabetics have increased incidence of
      depression, and vice versa. In addition: depressive, non-diabetic patients have
      several insulin- and glucose-metabolism disturbances, probably exerting a
      compensatory reaction to the malfunction in the depressed brain as these
      disturbances are normalised in remission. After the discovery of PET-scanning,
      such studies have shown that patients with depressive disorder have reduced
      glucose metabolism in frontal parts of the brain. The present hypothesis regards
      the PET findings as observations of the primary pathophysiology of depression.
      Furthermore: two studies of post mortem samples from depressed patients show
      reduced numbers of astroglia. This is in accordance to the mentioned insulin
      disturbances, as only astroglia, not neurons, have insulin-sensitive glucose
      metabolism. Hence: the astroglia, not necessarily the neurons, are proposed to be
      the type of cells in which the disease resides. Most probably depressive disorder
      is a multitude of diseases, explaining the apparent multitude of symptoms, and
      the fact that different patients do respond to different drugs. Therefore: one
      can only formulate the hypothesis by mentioning a common denominator to these
      specific malfunctions, namely: disturbed glucose metabolism in the depressed
      brain. The present paper reviews several findings and proposes that attenuated
      cerebral glucose metabolism in frontal parts of the brain, in the astroglia, is
      the cause of depressive disorder.

PMID- 16978795
TI  - Normal-tension glaucoma and Alzheimer's disease: Helicobacter pylori as a
      possible common underlying risk factor.

PMID- 16978796
TI  - The dawn of science-based moral reasoning.
AB  - In 1998, Edward O. Wilson discussed the biological basis of morality, pointed out
      that the analysis of its material origins should enable us to fashion a wise
      ethical consensus, and predicted the dawn of science-based moral reasoning. This
      article testifies that his prediction was right. Morality, being based on
      altruism and collaboration, evolved as a socially advantageous biological
      phenomenon aimed at ensuring the survival of our species, which was structured in
      small groups at high risk of extinction for the 99.5% of its existence. In the
      last 0.5%, the advent of agriculture resulted in a demographic explosion that
      impaired human beings' moral discernment, because the socially detrimental
      consequences of immoral actions, which had been recognised and condemned promptly
      in small groups consisting of a few tens of members, were diluted among millions
      of untouched individuals, thereby becoming less easily recognisable. Nowadays, to
      test the supposed morality of individual actions and government policies, we
      should use reason or, in doubtful cases, mathematical modelling to determine
      their predictable effects on the survival of small theoretical communities.
      Unless we untenably claim that the unlikelihood of extinction of today's immense
      societies entitles us to overturn the meaning of morality, all actions and
      policies that would cause the extinction of small communities should be regarded
      as indisputably immoral. This article also presents some examples of science
      based moral arguments showing the immorality of restrictions and bans on research
      with human embryonic stem cells and demonstrates that the old concept of the
      "naturalistic fallacy", which philosophers frequently invoke to dismiss any
      scientific approach to morality, is no longer tenable, because it increasingly
      emerges to be a proof of what may well be defined the "philosophical fallacy".

PMID- 16978797
TI  - Abnormal hormonal control of gut hydrolytic enzymes causes autoimmune attack on
      the CNS by production of immune-mimic and adjuvant molecules: A comprehensive
      explanation for the induction of multiple sclerosis.
AB  - Multiple sclerosis (MS) is generally thought to be caused by an autoimmune attack
      on central nervous system (CNS) myelin. A microorganism containing a mimic of an
      immunogenic region of a myelin protein initiates the autoimmune process. However,
      no specific "MS" microorganism has been found. Recently a large number of normal
      human gut bacteria were found to possess different encephalitogenic mimics. A
      hypothesis is presented that the autoimmune process is started by abnormal
      proteolytic digestion of these bacteria. Sufficient quantities of the mimics are
      produced to be recognized by the immune system. Since proteolytic processes in
      the gut are strictly controlled, it is proposed that the MS process is triggered
      by abnormal hormonal control of gut proteolytic enzymes. It has previously been
      suggested that the recognition of CNS myelin antigens by activated MS immune
      cells is facilitated by proteolytic processing of myelin proteins. The CNS
      proteases are also under rigid control and these control processes are the same
      as is in the gut. Therefore, MS clinical activity is the result of improper
      hydrolytic degradation in the brain-gut axis caused by an abnormal hormonal
      variation.

PMID- 16978798
TI  - The metabolic syndrome and the Maillard reaction. An introduction.
AB  - With the rapid increase of life expectancy in western societies, appeared also a
      new phenomenon, obesity, which took during the recent decades pandemic
      dimensions. One of the consequences was the appearance of type II diabetes in
      much younger persons than before. The result of intensive research in this field
      over the last decades led, among other achievements to the identification of
      biological and molecular symptoms which together were reclassified as the
      "metabolic syndrome". Questionable as far as its originality is concerned, it did
      however good service to practitioners by formulating criteria for diagnostic and
      therapeutical purposes. Among the underlying biochemical mechanisms the Maillard
      reaction, the non enzymatic glycosylation of proteins and nucleotide bases
      followed by the formation of advanced glycation and products (AGE-s) plays an
      important role. Several recent experimental results confirm this statement, some
      of them are published in this issue. The reviews and original contributions form
      together an up to date report on this important pathology and support again the
      importance of posttranslational and environmental factors influencing gene
      expression and cellular functions.

PMID- 16978799
TI  - Advanced glycation endproducts (AGEs): Pharmacological inhibition in diabetes.
AB  - AGE inhibitors may act by various mechanisms at different steps of advanced
      glycation endproduct (AGE) formation (depending on oxidative stress and/or
      carbonyl stress) and AGE-mediated damage: trapping of reactive dicarbonyl
      species; antioxidant activity by transition metal chelation; other antioxidant
      activity including free radical scavenging; AGE cross-link breaking; AGE receptor
      (RAGE) blocking; RAGE signaling blocking; glycemia reduction by anti-diabetic
      therapy; aldose reductase inhibition; shunting of trioses-P towards the pentose-P
      pathway by transketolase activation. Most of the inhibitors have several sites of
      action. Practically one can distinguish drugs specifically developed as AGE
      inhibitors or AGE breakers; RAGE and receptor signaling blockers; other
      therapeutic compounds which were found subsequently to possess also AGE inhibitor
      activity, including dietary antioxidants. Encouraging results obtained in studies
      of various AGE inhibitors, conducted in vitro and in diabetic animals, are
      summarized in this review. However most of the clinical trials have been more or
      less disappointing, in part because of side effects; the long-term therapeutic
      interest of the most recently developed AGE inhibitors or breakers remains to be
      demonstrated in diabetes.

PMID- 16978800
TI  - Maintenance of delay of gratification by four chimpanzees (Pan troglodytes): the
      effects of delayed reward visibility, experimenter presence, and extended delay
      intervals.
AB  - Previous research in our laboratory has demonstrated that chimpanzees can delay
      gratification by inhibiting consumption of available food items for as long as 3
      min as an experimenter transfers additional food items from a transparent
      container to a bowl placed in front of the subject. In this study, we examined
      the influence of the visibility of the food source, as well as the presence of
      the experimenter, on four chimpanzees' self-control in this paradigm. In
      Experiment 1 an experimenter transferred 15 preferred food items between a
      distant opaque container and a bowl placed in front of the subject. In Experiment
      2 we tested the chimpanzees with an automated system that (in the absence of the
      experimenter) transferred up to 36 highly preferred food items from a universal
      food dispenser to a container located either inside or outside of the subject's
      enclosure. There were no differences in self-directed behaviors or attentiveness
      to the food items between the self-imposed and externally imposed delay
      conditions. A final experiment with the automated paradigm indicated that
      individuals could delay gratification for up to 11min in order to obtain all 36
      food items.

PMID- 16978801
TI  - The potential for accurately measuring behavioral and economic dimensions of
      consumption, prices, and markets for illegal drugs.
AB  - There are numerous analytic and methodological limitations to current measures of
      drug market activity. This paper explores the structure of markets and individual
      user behavior to provide an integrated understanding of behavioral and economic
      (and market) aspects of illegal drug use with an aim toward developing improved
      procedures for measurement. This involves understanding the social processes that
      structure illegal distribution networks and drug users' interactions with them.
      These networks are where and how social behaviors, prices, and markets for
      illegal drugs intersect. Our focus is upon getting an up close measurement of
      these activities. Building better measures of consumption behaviors necessitates
      building better rapport with subjects than typically achieved with one-time
      surveys in order to overcome withholding and underreporting and to get a
      comprehensive understanding of the processes involved. This can be achieved
      through repeated interviews and observations of behaviors. This paper also
      describes analytic advances that could be adopted to direct this inquiry
      including behavioral templates, and insights into the economic valuation of labor
      inputs and cash expenditures for various illegal drugs. Additionally, the paper
      makes recommendations to funding organizations for developing the mechanisms that
      would support behavioral scientists to weigh specimens and to collect small
      samples for laboratory analysis-by providing protection from the potential for
      arrest. The primary focus is upon U.S. markets. The implications for other
      countries are discussed.

PMID- 16978802
TI  - A new parameter to study compositional properties of non-coding regions in
      eukaryotic genomes.
AB  - Genomes are characterized by global and local compositional properties that are
      interesting in an evolutionary perspective but also provide useful information
      for the identification of some functional elements. Following previous studies,
      in this work we investigated compositional properties of non-coding sequences in
      four eukaryotic genomes (C. elegans, D. melanogaster, M. musculus, H. sapiens).
      We developed a procedure based on Principal Component Analysis (PCA) and Linear
      Discriminant Analysis (LDA) to identify pentamers that are over-represented in
      introns (intron vocabulary) and to define a new parameter (LD) that reflects
      oligonucleotide composition of a given sequence. We analyzed genomic sequences
      and we found that all non-coding parts of a genome are characterized by similar
      LD values. Furthermore, we used the new parameter to analyze potentially
      regulatory regions. We extracted non-redundant sets of promoter sequences for D.
      melanogaster and H. sapiens and we studied their compositional (G+C content and
      LD parameter) and conformational (bendability propensity) properties. We found
      that regions immediately surrounding transcription start sites are
      distinguishable because of their %G+C, LD and bendability values.

PMID- 16978803
TI  - In vitro susceptibilities of field isolates of Mycoplasma mycoides subsp.
      mycoides large colony type to 15 antimicrobials.
AB  - In vitro susceptibilities of 16 Mycoplasma mycoides subsp. mycoides large colony
      type field isolates to 15 antimicrobial agents were determined using a broth
      microdilution method. The most effective antimicrobials were fluoroquinolones,
      tetracyclines and macrolides, with MIC values under 2 microg/ml. Resistance to
      nalidixic acid, gentamicin, streptomycin and spectinomycin was observed.

PMID- 16978804
TI  - Longitudinal assessment of heart rate variability in very low birth weight
      infants during their NICU stay.
AB  - BACKGROUND: Maturation of the autonomic nervous system has not been studied in
      high-risk very low birth weight (VLBW) infants in the first few weeks of life.
      AIM: To characterize developmental changes in autonomic nervous system activity
      of high-risk VLBW infants from 23 to 38 weeks post-menstrual age by measuring
      heart rate variability (HRV). STUDY DESIGN AND SUBJECTS: In this prospective
      cohort study 38 infants admitted to Children's Memorial Hermann Hospital NICU
      were longitudinally followed weekly or biweekly. Heart period data were recorded
      while infants were resting in active sleep. OUTCOME MEASURES: Growth of spectral
      power of HRV in low-frequency (0.05-0.25 Hz) and high-frequency (0.25-1.00 Hz)
      bands was modeled with linear mixed-effects models. The high-frequency power
      provides a measure of respiratory sinus arrhythmia (RSA). RESULTS: Low-frequency
      power increases with post-menstrual age, and intubated infants have lower HRV.
      The increase in low-frequency power is faster (0.50+/-0.12 dB/week) than the
      increase in RSA (0.17+/-0.09 dB/week). CONCLUSION: This longitudinal data
      exhibits developmental maturation of the RSA and of the low-frequency power of
      HRV in high-risk VLBW infants.

PMID- 16978805
TI  - The effect of a fructo-oligosaccharide supplemented formula on gut flora of
      preterm infants.
AB  - AIM: The intestinal flora of breast-fed infants is generally dominated by
      bifidobacteria which have beneficial properties. Their presence is due to various
      components of breast milk, including prebiotic substances. This prospective
      double-blind study compared the numbers of bifidobacteria in the stool flora of
      bottle-fed preterm infants randomized to receive for 14 days either a formula
      with prebiotic fructo-oligosaccharides at a concentration of 0.4 g/dL or the same
      formula with maltodextrin as a placebo. METHODS: Within 0-14 days after birth, 56
      healthy bottle-fed infants were enrolled to receive either the prebiotic or
      placebo. Faecal samples were taken at inclusion day and at study day 7. The
      number of bifidobacteria in the stools, stool characteristics and somatic growth
      were recorded during the study. RESULTS: In the group fed fructo
      oligosaccharides, both the numbers of bifidobacteria in the stools and the
      proportion of infants colonized with them were significantly higher as compared
      to the placebo group (p=0.032 and p=0.030 respectively). There was also a higher
      number of bacteroids in the fructo-oligosaccharide group as compared to the
      placebo (p=0.029). At the same time, reduction was noted in the numbers of
      Escherichia coli and enterococci. (p=0.029, and p=0.025, respectively).
      Supplementation had also significant influence on stool frequency per day
      (p=0.0080). CONCLUSION: An infant formula containing a small quantity of
      prebiotic oligosaccharides is well accepted and leads to rapid growth of
      bifidobacteria in the gut of bottle-fed preterm infants while decreasing the
      numbers of pathogenic microorganisms.

PMID- 16978806
TI  - Modulatory effects of Aroclors 1221 and 1254 on bone turnover and vertebral
      histology in intact and ovariectomized rats.
AB  - Polychlorinated biphenyls (PCBs) are persistent environmental pollutants. Two PCB
      mixtures, Aroclors 1221 and 1254 have been suggested to have estrogenic and anti
      estrogenic properties, respectively. We have examined whether these PCB mixtures
      modulate bone turnover and vertebral histology in intact and ovariectomized (ovx)
      rat models. Thirty-two adult female rats were divided into four groups
      subcutaneously receiving 4% DMSO (control), A1221 (10 mg/kg), A1254 (10 mg/kg)
      oestradiol (E2, 30 microg/kg). These compounds were injected to the animals for a
      period of 6 weeks at two daily intervals. In the second model, rats (n=32) were
      ovx and allowed to recover for a period of 3 weeks. Control group received
      vehicle (4% DMSO) alone. Remaining rats were divided into three groups and
      injected (s.c.) with A1221, A1254 and E2 for 5 weeks. Urine samples were
      collected prior to end of the experiments. Then, all animals were decapitated.
      Serum parathyroid hormone (PTH), calcitonin and osteocalcin levels were
      determined by immunoradiometric method. Serum concentrations of alkaline
      phosphatase (ALP), calcium and inorganic phosphate were determined by enzymatic
      colorimetric method. Urinary deoxypyridinoline (DPD) was measured by ELISA.
      Lumbar vertebrae (L2) of all animals were dissected out and processed for light
      microscopy. Levels of urinary DPD were significantly lowered in E2 -treated
      intact rats (p<0.001). Ovx significantly increased urinary DPD excretion (p<0.01)
      compared to intact control values. Administration of A1221 and A1254 had no
      significant effects in intact rats, however, they significantly reduced (p<0.05)
      and increased (p<0.001) urinary DPD levels in ovx rats, respectively. Neither of
      the PCB mixtures significantly changed serum osteocalcin and ALP levels in intact
      or ovx rats (except A1221 increased ALP in intact model, p<0.01). Both PCB
      mixtures had differential effects on serum PTH, calcitonin, calcium and inorganic
      phosphate concentrations. Treatment with A1221 reversed the adverse effects of
      ovariectomy on L2 histology. However, A1254 produced necrotic areas in vertebral
      bone, and this effect was expanded in ovx animals. Our findings suggest that both
      Aroclor compounds interfere with bone turnover mechanisms, particularly in ovx
      rats.

PMID- 16978807
TI  - Overexpression of NQO1 protects human SK-N-MC neuroblastoma cells against
      dopamine-induced cell death.
AB  - NAD(P)H quinone oxidoreductase 1 (NQO1) can metabolize dopamine-derived quinones
      (DAQ) and absence of NQO1 due to the NQO1*2 polymorphism has been suggested to be
      a risk factor for Parkinson's disease. In order to define whether NQO1 plays a
      protective role in dopamine toxicity, we have examined the potential role of NQO1
      in the SK-N-MC human neuroblastoma cell line. SK-N-MC cells were stably
      transfected with NQO1 to generate stable clones with NQO1 enzymatic activity of
      245 nmol/mgmin while vector control and parental cells had NQO1 activities of
      less than 12 nmol/mgmin. Incubation of dopamine for 24 h in both parental and
      vector control SK-N-MC cells resulted in 85% and 72% cell death as assessed by
      annexin-V/propidium iodide analysis. In agreement, 88% and 84% of parental and
      vector control cells, respectively underwent loss of mitochondrial membrane
      potential (MMP) assessed by tetramethylrhodamine ethyl ester. In contrast, NQO1
      transfected cells were resistant to dopamine toxicity and both cell death and
      loss of MMP were markedly abrogated in NQO1-transfected SK-N-MC cells. When
      dopamine was added to medium, oxygen uptake could be detected indicating
      autoxidation with concomitant formation of oxygen radicals and quinones. However,
      dopamine-induced cell death was not affected by the inclusion of either
      superoxide dismutase or catalase suggesting that superoxide and hydrogen peroxide
      were not involved in toxicity. Quinones formed in medium may exert toxicity
      extracellularly or intracellularly but the protective role of NQO1 argues for an
      intracellular mechanism. In summary, transfection of SK-N-MC cells with NQO1
      protects against dopamine-induced toxicity.

PMID- 16978808
TI  - DNA-DNA cross-links contribute to the mutagenic potential of the mycotoxin
      patulin.
AB  - The mycotoxin patulin (PAT), which occurs in various foods, induces mutations in
      cultured mammalian cells. However, the mechanism underlying the mutagenic
      potential of PAT is far from clear. In order to further clarify the mutagenic
      mode of action of PAT, we investigated the potential of PAT to induce DNA strand
      breaks, oxidative DNA modifications, and DNA-DNA cross-links using an alkaline
      filter elution technique and a fluorescence-based assay. In concentrations known
      to induce mutations in V79 cells (0.5-2.5 microM), PAT also induced DNA-DNA cross
      links. In contrast, no effect on the number of DNA strand breaks (i.e., DNA
      single and double strand breaks as well as alkali-labile sites) or fpg-sensitive
      sites (i.e., oxidative DNA modifications) was observed in the non-cytotoxic
      concentration range. Thus, the present study demonstrates for the first time the
      direct reactivity of PAT towards DNA in a cellular system, which might have
      implications for the toxicological evaluation of this widespread mycotoxin.

PMID- 16978809
TI  - Investigation of excipient and processing on solid phase transformation and
      dissolution of ciprofloxacin.
AB  - Ciprofloxacin, a very slightly soluble antibiotics, is known to exist as both
      anhydrous and hydrous forms. This study was carried out to investigate the solid
      phase transformation of ciprofloxacin during conventional formulation processing
      that impacts the performance of solid dosage forms. In addition, alternative
      processing and formulation options were also evaluated to circumvent phase
      transformation. Anhydrate and hydrate of ciprofloxacin were characterized using
      differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder
      X-ray diffraction (PXRD) and powder dissolution. As expected, the anhydrate
      exhibited significantly higher dissolution rate than the hydrate. However, it
      rapidly converted to the hydrate upon exposure to aqueous medium. Interestingly,
      premixing the anhydrate with HPMC in the presence of water or ethanol was found
      to inhibit the processing-induced phase transition. Further studies demonstrated
      that wet granulation could be an option for preparing tablets with high loading
      of ciprofloxacin anhydrate through proper selection of excipients and control of
      processing conditions. Dissolution study of ciprofloxacin in HPMC based extended
      release matrix tablets indicated different dissolution rates between tablets
      containing the anhydrate and hydrate, suggesting transformation to the hydrate
      was significantly inhibited by HPMC in the gel layer of the hydrated tablets.

PMID- 16978810
TI  - Isotretinoin-loaded solid lipid nanoparticles with skin targeting for topical
      delivery.
AB  - The purpose of this study was to construct isotretinoin-loaded SLN (IT-SLN)
      formulation with skin targeting for topical delivery of isotretinoin. PRECIROL
      ATO 5 was selected as the lipid of SLN. Tween 80 and soybean lecithin were used
      as the surfactants to stabilize SLN. The hot homogenization method was performed
      to prepare the drug-loaded SLN. The various formulations were characterized by
      photon correlation spectroscopy and all the SLN formulations had low average size
      between 30 and 50 nm. Transmission electron microscopy studies showed that the IT
      SLN formulation had a spherical shape. All the formulations had high entrapment
      efficiency ranging from 80% to 100%. The penetration of isotretinoin from the IT
      SLN formulations through skins and into skins were evaluated in vitro using Franz
      diffusion cells fitted with rat skins. The in vitro permeation data showed that
      all the IT-SLN formulations can avoid the systemic uptake of isotretinoin in
      skins, however the control tincture had a permeation rate of 0.76+/-0.30 microg
      cm(-2)h(-1) through skins. The IT-SLN consisting of 3.0% PRECIROL ATO 5, 4.0%
      soybean lecithin and 4.5% Tween 80 could significantly increased the accumulative
      uptake of isotretinoin in skin and showed a significantly enhanced skin targeting
      effect. The studied IT-SLN showed a good stability. These results indicate that
      the studied IT-SLN formulation with skin targeting may be a promising carrier for
      topical delivery of isotretinoin.

PMID- 16978811
TI  - Conformational polymorphism in bicalutamide.
AB  - Two crystalline forms (forms I and II) and an amorphous phase of bicalutamide
      were fully characterized through combined results of differential scanning
      calorimetry, X-ray powder and single crystal diffraction and Raman spectroscopy.
      Each polymorph crystallizes with one molecule in the asymmetric unit and the
      molecular conformations are quite different between them. The main difference is
      provided by C12-C11-S8-C5 torsion angle, which assumes a value of -88.3(4)
      degrees (-Syn-Clinal) and 72.5(4) degrees (+Syn-Clinal) in forms I and II,
      respectively. Consequently, molecules in form I show an open folding and
      molecules in form II a closed one. The relative stability between forms I and II
      is presented in an energy versus temperature diagram, where forms I and II are
      considered as a monotropic system, being form I the more stable one. The
      amorphous phase was observed very metastable and it converts to form II
      spontaneously at RT in around a week.

PMID- 16978812
TI  - Detection of interaural correlation by neurons in the superior olivary complex,
      inferior colliculus and auditory cortex of the unanesthetized rabbit.
AB  - A critical binaural cue important for sound localization and detection of signals
      in noise is the interaural time difference (ITD), or difference in the time of
      arrival of sounds at each ear. The ITD can be determined by cross-correlating the
      sounds at the two ears and finding the ITD where the correlation is maximal. The
      amount of interaural correlation is affected by properties of spaces and can
      therefore be used to assess spatial attributes. To examine the neural basis for
      sensitivity to the overall level of the interaural correlation, we identified
      subcollicular neurons and neurons in the inferior colliculus (IC) and auditory
      cortex of unanesthetized rabbits that were sensitive to ITDs and examined their
      responses as the interaural correlation was varied. Neurons at each brain level
      could show linear or non-linear responses to changes in interaural correlation.
      The direction of the non-linearities in most neurons was to increase the slope of
      the response change for correlations near 1.0. The proportion of neurons with non
      linear responses was similar in subcollicular and IC neurons but increased in the
      auditory cortex. Non-linear response functions to interaural correlation were not
      related to the type of response as determined by the tuning to ITDs across
      frequencies. The responses to interaural correlation were also not related to the
      frequency tuning of the neuron, unlike the responses to ITD, which broadens for
      neurons tuned to lower frequencies. The neural discriminibility of the ITD using
      frozen noise in the best neurons was similar to the behavioral acuity in humans
      at a reference correlation of 1.0. However, for other reference ITDs the neural
      discriminibility was more linear and generally better than the human
      discriminibility of the interaural correlation, suggesting that stimulus rather
      than neural variability is the basis for the decline in human performance at
      lower levels of interaural correlation.

PMID- 16978813
TI  - Predicting mechanical damage to the organ of Corti.
AB  - The potential for pharmacological intervention to ameliorate the effects of
      exposure to intense auditory stimulation is a truly exciting possibility. In
      theory, the effects of intense stimulation could be primarily a function of
      mechanical stress and its sequelae or possibly metabolic exhaustion. Conceivably,
      specific pharmacological therapies might be more effective following different
      types of insult, depending on the loss mechanism(s) involved. The Auditory Hazard
      Assessment Algorithm for the Human (AHAAH), a first-principles mathematical model
      for the ear, has been developed specifically to predict hazard at high
      intensities based on basilar membrane displacement. Validation studies have
      proven it to be accurate in rating risk for the human ear. AHAAH is available for
      download on the Internet. In the present context it was used to propose analytic
      stimuli that would help to elucidate the loss mechanisms and also to identify
      exposures for the clinician that should be considered as sufficiently hazardous
      to warrant potential pharmacological intervention either before or after the
      exposure.

PMID- 16978814
TI  - Cell death after co-administration of cisplatin and ethacrynic acid.
AB  - Ethacrynic acid (EA) significantly enhances the ototoxic effects of cisplatin. To
      gain insights into the mechanisms underlying Cis/EA ototoxicity, cochleas were
      labeled with several apoptotic markers. Cis/EA treatment caused extensive outer
      hair cell (OHC) and inner hair cell (IHC) damage; OHC lesions decreased from the
      base towards apex of the cochlea whereas the IHC lesion was relatively constant
      (25-60%) along the length of the cochlea. Propidium iodide labeled OHC nuclei
      appeared relatively normal at 6h post-treatment, were condensed and fragmented at
      12h post-treatment and were frequently missing 48 h post-treatment. Initiator
      caspase 8, associated with membrane death receptors, and TRADD, a protein that
      recruits caspase 8, were present in OHC at 6h post-treatment. Caspase 8 labeling
      increased from 6 to 24h, but was largely absent at 48 h post-treatment.
      Executioner caspase 3 and caspase 6, which lie downstream of caspase 8, were
      expressed in OHC 12-24h post-treatment. Initiator caspase 9, associated with
      mitochondrial damage, was only expressed at low levels at 48 h post-treatment.
      These results suggest that the rapid onset of Cis/EA induced programmed cell
      death is initiated by membrane death receptors associated with TRADD and caspase
      8.

PMID- 16978815
TI  - Hypoglycemic, vasorelaxant and hepatoprotective effects of Cochlospermum
      vitifolium (Willd.) Sprengel: a potential agent for the treatment of metabolic
      syndrome.
AB  - Cochlospermum vitifolium (Willd.) Sprengel is a Mexican medicinal plant that is
      used in the folk medicine for the treatment of hypertension, diabetes, hepatitis
      and related diseases. The purpose of the present study was to assess the
      pharmacological properties of different extracts from Cochlospermum vitifolium
      bark as potential agent for the treatment of some factors related with metabolic
      syndrome (MS), a complex disease produced for several pathophysiological factors
      such as visceral fat obesity, insulin resistance, hypertension, dyslipidemia and
      liver steatosis. Hexane (HECv), dichloromethane (DECv) and methanol (MECv)
      extracts were subjected to some pharmacological assays to determine their
      vasorelaxant and hypoglycemic activity. On the other hand, MECv was also
      evaluated to determine its hepatoprotective effect on sub-chronic experimental
      assay. HECv showed a significant endothelium-independent relaxation on rat aorta
      rings (intact endothelium: IC(50)=14.42+/-5.90 microg/mL, E(max)=92.71+/-8.9%;
      denuded endothelium: IC(50)=27.94+/-4.0 microg/mL, E(max)=78.68+/-4.6%) and MECv
      produced an endothelium-dependent relaxation (IC(50)=21.94+/-6.87 microg/mL,
      E(max)=79.12+/-7.80%) on this tissue. Furthermore, HECv (at a dose of 120 mg/kg)
      also showed a significant decrease of blood glucose levels (p<0.05) on
      normoglycemic rats. Moreover, MECv (at a dose of 100 mg/kg) also was administered
      to bile duct-obstructed rats to determine its hepatoprotective activity, showing
      a statistically significant decrease of serum glutamic-pyruvic transaminase (PGT,
      45%) and alkaline phosphatase (APh, 15%) (p<0.05). Finally, we obtained a
      crystalline polyphenolic compound from MECv by spontaneous precipitation. Those
      crystals were identified as (+/-)-naringenin by X-ray diffraction, NMR, IR and GC
      MS techniques. Results suggest that Cochlospermum vitifolium could be used as a
      potential agent against MS since it shows hypoglycemic, vasorelaxant and
      hepatoprotective properties.

PMID- 16978816
TI  - Anti-allergic activity of some selected plants in the Zingiberaceae family.
AB  - Ethanolic and water extracts, together with volatile oils from the rhizomes of
      six selected Zingiberaceous plants, including Curcuma mangga, Kaempferia galanga,
      Kaempferia parviflora, Zingiber cassumunar, Zingiber officinale and Zingiber
      zerumbet were investigated for their anti-allergic activities using a RBL-2H3
      cell line. The ethanolic (EtOH) extract of Kaempferia parviflora exhibited the
      most potent anti-allergic effect against antigen-induced beta-hexosaminidase
      release as a marker of degranulation in RBL-2H3 cells, with an IC(50) value of
      10.9 microg/ml, followed by Zingiber cassumunar (EtOH, IC(50)=12.9 microg/ml) and
      Curcuma mangga (water, IC(50)=36.1 microg/ml). The volatile oils of these six
      plants were apparently inactive (IC(50)>100 microg/ml). The crude extracts were
      also tested on beta-hexosaminidase activity to clarify whether their effects were
      due to the inhibition of enzyme activity or of degranulation. As a result, the
      plant extracts were inactive against the enzyme activity of beta-hexosaminidase.
      These findings support the use in Thai traditional medicine of these selected
      Zingiberaceous plants, especially Kaempferia parviflora and Zingiber cassumunar,
      for treatment of allergy and allergic-related diseases.

PMID- 16978817
TI  - Acute and subacute toxicity of Salvia scutellarioides in mice and rats.
AB  - The acute and subacute toxicity of the aqueous extract of Salvia scutellarioides
      (Lamiaceae) was studied in mice and rats. In the acute toxicity test, oral
      administration of 2g/kg of Salvia scutellarioides produced neither mortality nor
      changes in behavior or any other physiological activities. In subacute toxicity
      studies, no mortality was observed when the two doses of 1 or 2g/kgday of aqueous
      extract of Salvia scutellarioides extract were administered orally for a period
      of 28 days. In the blood chemistry analysis, no significant changes occurred,
      including glucose, creatinine, blood urea nitrogen (BUN), aspartate transaminase
      (AST), alanine transaminase (ALT), potassium, sodium, chloride, calcium,
      phosphorus, conjugated billirrubin, total billirrubin, total cholesterol, high
      density lipoprotein (HDL), triglycerides, total protein, albumin, prothrombin
      time (PT) and thromboplastin partial time (PTT) of both sexes. Hematological
      analysis showed no differences in any of the parameters examined (WBC count,
      platelet and hemoglobin estimation) in either the control or treated group of
      both sexes. The urinalysis was negative for glucose, ketonic bodies, casts, red
      blood cells, and albumin in the control and treatment groups. There were no
      significant differences in the body and organ weights between controls and
      treated animals of both sexes. Pathologically, neither gross abnormalities nor
      histopathological changes were observed.

PMID- 16978819
TI  - Breath alcohol concentration determined with a new analyzer using free exhalation
      predicts almost precisely the arterial blood alcohol concentration.
AB  - A new breath alcohol (ethanol) analyzer has been developed, which allows free
      exhalation, standardizes measured exhaled alcohol concentration to fully
      saturated water vapor at a body temperature of 37 degrees C (43.95 mg/L) and
      includes a built-in self-calibration system. We evaluated the performance of this
      instrument by comparing standardized alcohol concentration in freely expired
      breath (BrAC) with arterial (ABAC) and venous (VBAC) blood alcohol concentrations
      in fifteen healthy volunteers who drank 0.6 g of alcohol per kg body weight. The
      precision (coefficient of variation, CV) of the analyzer based on in vivo
      duplicate measurements in all phases of the alcohol metabolism was 1.7%. The
      ABAC/BrAC ratio was 2251+/-46 (mean+/-S.D.) in the post-absorptive phase and the
      mean bias between ABAC and BrAC x 2251 was 0.0035 g/L with 95% limits of
      agreement of 0.033 and -0.026. The ABAC and BrAC x 2251 were highly correlated
      (r=0.998, p<0.001) and the regression relationship was ABAC = 0.00045 + 1.0069 x
      (BrAC x 2251) indicating excellent agreement and no fixed or proportional bias.
      In the absorption phase, ABAC exceeded BrAC x 2251 by at most 0.04+/-0.03 g/L
      when tests were made at 10 min post-dosing (p<0.05). The VBAC/BrAC ratio never
      stabilized and varied continuously between 1834 and 3259. There was a
      proportional bias between VBAC and BrAC x 2251 (ABAC) in the post-absorptive
      phase (p<0.001). The pharmacokinetic analysis of the elimination rates of alcohol
      and times to zero BAC confirmed that BrAC x 2251 and ABAC agreed very well with
      each other, but not with VBAC (p<0.001). We conclude that this new breath
      analyzer using free exhalation has a high precision for in vivo testing. The BrAC
      reflects very accurately ABAC in the post-absorption phase and substantially well
      in the absorption phase and thereby reflects the concentration of alcohol
      reaching the brain. Our findings highlight the magnitude of arterio-venous
      differences in alcohol concentration and support the use of breath alcohol
      analyzers as a stand-alone test for medical and legal purposes.

PMID- 16978818
TI  - Mitochondrial involvement in Atuna racemosa induced toxicity.
AB  - Our group has developed a system to extract information regarding potential novel
      pharmaceuticals from historic herbal texts. We have shown that one of the plants
      identified through this technique has the purported antibacterial properties
      suggested by the text. Here, the toxicity of this antibacterial extract was
      examined. Using a Jurkat cell model, a therapeutic window between the minimal
      inhibitory concentration for Gram-positive bacteria and the dose-dependent
      toxicity of the Atuna racemosa extract was established. Using cells with a
      mutated caspase 8, it was shown that the toxicity does not involve caspase 8.
      However, by transmission electron microscopy and a potentiometric dye, the
      toxicity was shown to involve the mitochondria. This toxicity also resulted in
      DNA cleavage and activation of caspase 3. This work suggests that the extract,
      originally reported as an antimicrobial therapeutic in a 400-year-old Dutch
      herbal text, may maintain a therapeutic window as an antibiotic. Furthermore,
      this work shows toxicity would occur in a mitochondrial dependent fashion.

PMID- 16978820
TI  - Molecular correlates of age-specific responses to traumatic brain injury in mice.
AB  - Aged traumatic brain injury (TBI) patients suffer higher rates of mortality and
      disability than younger patients. Cognitive problems common to TBI patients are
      associated with damage to the hippocampus, a central locus of learning and
      memory. To investigate the molecular mechanisms of age-related vulnerability to
      brain injury in a mouse model of TBI, we studied the effects of TBI on
      hippocampal gene expression in young and aged mice. Young and aged male C57Bl/6
      mice were subjected to sham injury or TBI and sacrificed 24 h post-injury. We
      used laser capture microdissection to obtain pure populations of neurons from the
      CA1, CA3, and dentate gyrus subfields of the hippocampus. We compared injury
      induced gene expression in hippocampal neurons of young and aged mice using
      quantitative ribonuclease protection assay analysis of linearly amplified mRNA
      from laser captured neurons. Both increased age and TBI were associated with
      increased expression of neuroprotective (brain-derived neurotrophic factor), pro
      inflammatory (interleukin-1beta), and proapoptotic (caspase-3) genes in mouse
      hippocampal neurons. Our data support previous reports that suggested the CA3
      subregion is highly susceptible to fluid percussion TBI and that age-related
      changes in gene expression are one potential mechanism of increased vulnerability
      of the aged brain to TBI.

PMID- 16978821
TI  - Analysis of different beta-lactams antibiotics in pharmaceutical preparations
      using micellar electrokinetic capillary chromatography.
AB  - The potential of micellar electrokinetic capillary chromatography (MEKC) for
      analyzing nine beta-lactams antibiotics (cloxacillin, dicloxacillin, oxacillin,
      penicillin G, penicillin V, ampicillin, nafcillin, piperacillin, amoxicillin) in
      different pharmaceutical preparations, have been demonstrated. An experimental
      design strategy has been applied to optimize the main variables: pH and buffer
      concentration, concentration of the micellar medium, separation voltage and
      capillary temperature. Borate buffer (26mM) at pH 8.5 containing 100mM sodium
      dodecyl sulphate (SDS) was used as the background electrolyte. The method was
      validated. Linearity, limit of detection and quantitation and precision were
      established for each compound. The analysis of some of the beta-lactams in
      Orbenin capsules, Britapen tables and in Veterin-Micipen injectable, all used in
      human and veterinary medicine, have demonstrated the applicability of these
      technique for quality control in the pharmaceutical industry.

PMID- 16978822
TI  - Development of a multicommuted flow-through optosensor for the determination of a
      ternary pharmaceutical mixture.
AB  - The combination of multicommutation and flow-through multioptosensing is
      presented in this work as a powerful strategy for the routine analysis of active
      principles in pharmaceuticals. By coupling methodologies, the selectivity and
      sensitivity of optosensors is maintained, while the use of the multicommutation
      approach provides additional advantages, such as low reagent consumption, low
      waste generation and reduced human supervision. The potential of this integration
      is enhanced when implemented with multiwavelength detection mode. An UV sensor is
      here developed for the simultaneous determination of three widely used active
      principles: salicylamide, caffeine and propyphenazone. The measuring wavelengths
      were 276 nm for caffeine and propyphenazone, and 302 nm for salicylamide. The
      five three-way solenoid valves used in the system are controlled by Java-written
      home-made software. The sensor is based on the on-line selective retention of two
      of the three analytes on a precolumn placed just before the sensing zone and
      filled with the same solid support than the flow-through cell (C(18) silica gel).
      This approach allows the sequential arrival of the analytes to the sensing zone,
      so allowing their determination with only one sample injection. So, the use of
      C(18) placed, in both the precolumn and the flow-cell combines the advantages of
      the increase of sensitivity and selectivity in the detection solid zone with the
      additional increase of the selectivity in the precolumn. The sensor was applied
      to the determination of the analytes in several pharmaceutical preparation of the
      Spanish Pharmacopoeia, obtaining satisfactory results.

PMID- 16978823
TI  - Characterization of hydroxypropylmethylcellulose films using microwave non
      destructive testing technique.
AB  - The applicability of microwave non-destructive testing (NDT) technique in
      characterization of matrix property of pharmaceutical films was investigated.
      Hydroxypropylmethylcellulose and loratadine were selected as model matrix polymer
      and drug, respectively. Both blank and drug loaded hydroxypropylmethylcellulose
      films were prepared using the solvent-evaporation method and were conditioned at
      the relative humidity of 25, 50 and 75% prior to physicochemical characterization
      using microwave NDT technique as well as ultraviolet spectrophotometry,
      differential scanning calorimetry (DSC) and Fourier transform infrared
      spectroscopy (FT-IR) techniques. The results indicated that blank
      hydroxypropylmethylcellulose film exhibited a greater propensity of polymer
      polymer interaction at the O-H and C-H domains of the polymer chains upon
      conditioned at a lower level of relative humidity. In the case of loratadine
      loaded films, a greater propensity of polymer-polymer and/or drug-polymer
      interaction via the O-H moiety was mediated in samples conditioned at the lower
      level of relative humidity, and via the C-H moiety when 50% relative humidity was
      selected as the condition for sample storage. Apparently, the absorption and
      transmission characteristics of both blank and drug loaded films for microwave
      varied with the state of polymer-polymer and/or drug-polymer interaction
      involving the O-H and C-H moieties. The measurement of microwave NDT test at 8GHz
      was sensitive to the chemical environment involving O-H moiety while it was
      greatly governed by the C-H moiety in test conducted at a higher frequency band
      of microwave. Similar observation was obtained with respect to the profiles of
      microwave NDT measurements against the state of polymer-polymer and/or drug
      polymer interaction of hydroxypropylmethylcellulose films containing
      chlorpheniramine maleate. The microwave NDT measurement is potentially suitable
      for use as an apparent indicator of the state of polymer-polymer and drug-polymer
      interaction of the matrix.

PMID- 16978824
TI  - 18F-FDG PET/CT fusion imaging in paediatric solid extracranial tumours.
AB  - This paper aims at discussing the utility of 18F-FDG PET/CT in the evaluation of
      paediatric solid extracranial tumours. Following a brief discussion of the basic
      principles and methodology of PET/CT system, it reviews the main characteristics
      of the tumours that can be visualised with 18F-FDG PET and presents examples of
      cases where the combined use of 18F-FDG PET/CT fusion imaging helped in the
      management of patients. It will also discuss the physiologic biodistribution of
      18F-FDG, outlining the normal variants in the paediatric patients that may lead
      to misinterpretation.

PMID- 16978825
TI  - Flavonoid-mediated inhibition of intestinal ABC transporters may affect the oral
      bioavailability of drugs, food-borne toxic compounds and bioactive ingredients.
AB  - The transcellular transport of ingested food ingredients across the intestinal
      epithelial barrier is an important factor determining bioavailability upon oral
      intake. This transcellular transport of many chemicals, food ingredients, drugs
      or toxic compounds over the intestinal epithelium can be highly dependent on the
      activity of membrane bound ATP binding cassette (ABC) transport proteins, able to
      export the compounds from the intestinal cells. The present review describes the
      ABC transporters involved in the efflux of bioactive compounds from the
      intestinal cells, either to the basolateral blood side, facilitating absorption,
      or back into the intestinal lumen, reducing bioavailability. The role of the ABC
      transporters in intestinal transcellular uptake also implies a role for
      inhibitors of these transporters in modulation of the bioavailability upon oral
      uptake. The present paper focuses on the role of flavonoids as important
      modulators or substrates of intestinal ABC transport proteins. Several examples
      of such an effect of flavonoids are presented. It can be concluded that flavonoid
      mediated inhibition of ABC transporters may affect the bioavailability of drugs,
      bioactive food ingredients and/or food-borne toxic compounds upon oral uptake.
      All together it appears that the flavonoid-mediated interactions at the level of
      the intestinal ABC transport proteins may be an important mechanism for
      unexpected food-drug, food-toxin or food-food interactions. The overview also
      indicates that future studies should focus on i) in vivo validation of the
      flavonoid-mediated effects on bioavailability of drugs, toxins and beneficial
      bioactive food ingredients detected in in vitro models, and on ii) the role of
      flavonoid phase II metabolism in modulating the activity of the flavonoids to act
      as ABC transporter inhibitors and/or substrates.

PMID- 16978826
TI  - Analyses and perspectives in cancer immunotherapy.
AB  - Since the last two decades, rapid progress has been made in the field of cancer
      immunotherapy relevant to manipulation of adaptative cytotoxic T lymphocytes
      (CTLs) and innate immunity natural killer (NK) cells as well as antibodies. Many
      possibilities are now offered for therapeutic purposes contributing to better
      approaches in treatment of cancer.

PMID- 16978827
TI  - Microbial metabolism of caffeic acid and its esters chlorogenic and caftaric
      acids by human faecal microbiota in vitro.
AB  - Caffeic acid and its esters, chlorogenic and caftaric acids, are major dietary
      polyphenols present in various foods and beverages. Although caffeic acid is
      easily absorbed in the small intestine, its esterification with quinic acid, as
      in chlorogenic acid, decreases its gut absorption and increases the quantities
      reaching the colon and its microbiota. The microbial conversion of caftaric acid,
      the tartaric acid ester of caffeic acid, has not been studied earlier. In this
      work we compared the direct action of a human faecal microbiota on the metabolism
      of caffeic, chlorogenic and caftaric acids in an in vitro fermentation model. All
      substrates disappeared quickly and none of the free acids (caffeic, quinic or
      tartaric acids) were detected after 2 hours of incubation. Two major microbial
      metabolites were identified by HPLC-ESI-MS-MS as 3-hydroxyphenylpropionic (3-HPP)
      and benzoic acids (BA). Maximal levels of 3-HPP were reached after 2 h of
      fermentation and accounted for 9-24% of the dose of caffeic acid and its esters.
      BA was formed steadily throughout the incubation, accounting for 4-5% of the
      initial dose of the substrates after 24 h of incubation. The similarities in the
      metabolic patterns observed for caffeic, chlorogenic and caftaric acids suggest
      that esterification does not influence the metabolism of caffeic acid by the gut
      microbiota.

PMID- 16978828
TI  - Involvement of IFNbeta on IFNgamma and nitric oxide (NO) production by bone
      marrow (BM) cells in response to lipopolysaccharide.
AB  - Bone marrow (BM) cells fractioned in Percoll gradients yield a low-density
      fraction (Fr3) highly enriched in suppressor activity. Previously, it has been
      demonstrated that BM associated suppressor activity was mediated by early myeloid
      cells, through a mechanism dependent on endogenous IFNgamma and nitric oxide
      production after bacterial stimuli, e.g. lipopolysaccharide (LPS). However, the
      mechanism(s) through which the IFNgamma is produced in BM has not yet been fully
      elucidated. Therefore, in the present study we investigated the involvement of IL
      12, IL-18 and IFNbeta on the production of IFNgamma and nitric oxide in cultures
      of BM Fr3 cells, and characterized the IFNgamma-producing cells, in response to
      LPS. The results show that both IL-12 and IFNbeta, but not IL-18, are involved on
      IFNgamma production. However, only IFNbeta appears to be critical on nitric oxide
      production. Furthermore, we found that cells of the Thy1.2+CD3+ phenotype produce
      IFNgamma and are tightly involved on nitric oxide production by BM Fr3 cells. In
      conclusion, IFNbeta appears to be critical on IFNgamma- and nitric oxide
      production by BM cells in response to LPS, through a mechanism that is dependent
      on Thy1.2+CD3+ IFNgamma-producing cells.

PMID- 16978829
TI  - Inhibition of macrophage activation and phagocytosis by a novel NF-kappaB
      inhibitor, dehydroxymethylepoxyquinomicin.
AB  - Previously, we designed and synthesized a new NF-kappaB inhibitor,
      dehydroxymethylepoxyquinomicin (DHMEQ). In the present research we looked into
      the effect of DHMEQ on the activation of macrophages, especially on the
      phagocytotic activity of cells of the mouse macrophage-like cell line RAW264.7.
      DHMEQ inhibited lipopolysaccharide (LPS)-induced NF-kappaB activation by
      inhibiting its nuclear translocation from the cytoplasm. It also inhibited the
      expression of inducible NO synthase (iNOS) and nitric oxide (NO) production
      induced by LPS and interferon-gamma. Using enzyme-linked immunosorbent assays
      (ELISAs) we showed DHMEQ to inhibit LPS-induced secretion of IL-6, IL-12,
      interleukin-1beta (IL-1beta), and TNF-alpha. Furthermore, DHMEQ also inhibited
      the phagocytosis of fluorescently labeled Escherichia coli by RAW264.7 cells
      treated with LPS or IL-1beta, thus being the first evidence for the involvement
      of NF-kappaB in the regulation of phagocytosis by use of this inhibitor. Deletion
      of p65 by siRNA also inhibited the phagocytosis. DHMEQ inhibited the LPS-induced
      but not IL-1beta-induced phagocytosis of glass beads, indicating that activation
      of not only NF-kappaB but also Toll-like receptor 4 (TLR-4) is essential for the
      phagocytosis of E. coli. Previously we found that DHMEQ inhibited type 2 collagen
      induced rheumatoid arthritis and the growth of various human carcinomas in mice.
      It is thus likely that inhibition of macrophage activation is involved in the
      mechanism of these anti-inflammatory and antitumor activities of DHMEQ in mice.

PMID- 16978830
TI  - HIV and complement: hijacking an immune defense.
AB  - The complement system is a central player of the innate immune system. Activation
      of the complement system protects the host against pathogens. However,
      uncontrolled synthesis can be detrimental to host. This concise review summarizes
      the current understanding of the mechanism(s) of complement activation, the
      mechanism of C3 regulation, and the role of complement in human immunodeficiency
      virus (HIV) pathogenesis with emphasis on the cross-talk between HIV and
      complement system in NeuroAIDS and HIV-associated nephropathy (HIVAN).

PMID- 16978831
TI  - REMOVED: Glutathione prevents cytochrome P450 3A induction by dexamethasone in
      primary cultures of rat hepatocytes.
AB  - This article has been removed consistent with Elsevier Policy on Article
      Withdrawal. The Publisher apologies for any inconvenience this may cause.

PMID- 16978832
TI  - Abnormal personality and the mood and anxiety disorders: implications for
      structural models of anxiety and depression.
AB  - Substantial overlap exists between the mood and anxiety disorders. Previous
      research has suggested that their comorbidity can be explained by a shared factor
      (negative emotionality), but that they may also be distinguished by other unique
      components. The current study explicated these relations using an abnormal
      personality framework. Current diagnoses of major depression and several anxiety
      disorders were assessed in 563 Gulf War veterans. Participants also completed the
      schedule for nonadaptive and adaptive personality (SNAP) to determine how these
      disorders relate to abnormal personality traits. Analyses of individual diagnoses
      indicated that depression, generalized anxiety disorder (GAD), and post-traumatic
      stress disorder (PTSD) were more strongly related to personality than were other
      anxiety disorders. The Self-Harm Scale distinguished major depression from all
      other disorders, highlighting its significance for future structural models. Our
      results add to a growing body of evidence suggesting that GAD and PTSD have more
      in common with major depression than with their anxiety disorder counterparts.

PMID- 16978833
TI  - Paint thinner exposure inhibits testosterone synthesis and secretion in a
      reversible manner in the rat.
AB  - Occupational exposure and sniffing of toluene-based organic solvents is an
      important public health problem. In this study, we have investigated the effects
      of paint thinner inhalation on testosterone synthesis and secretion in the male
      rat. A control group inhaled normal air ventilation. The remaining animals were
      divided into three groups and exposed to paint thinner in a glassy cage for 15
      and 30 days (2 h/day). A group of rats was allowed to recover for 15 days after
      30 days of exposure. Toluene concentration (the largest constituent in thinner,
      66%) was set at 1500 ppm in the inhaled air. At the end, all animals were
      decapitated and blood samples obtained. Testes and seminal vesicles were removed
      and weighed out. Serum total testosterone levels were determined by
      chemiluminescence enzyme immunoassay. Testicular tissue specimens were processed
      for semi-quantitative evaluation of immunohistochemical testosterone staining and
      light microscopy. Intensity of immunostaining was evaluated on a scale between 0
      (no staining), 1 (minimal), 2 (mild), 3 (moderate) and 4 (strong staining). Serum
      testosterone levels (ng/ml) were decreased by 15-day (3.31+/-0.61) and 30-day
      (1.17+/-0.54, p<0.02) thinner exposure compared to the controls (3.91+/-1.03).
      Another group of rats exposed to thinner for 30 days and then allowed to recover
      for a period of 15 days had significantly elevated levels of testosterone values
      (3.77+/-1.1; p<0.05). Immunohistochemical testosterone staining of the cytoplasm
      of Leydig cells was moderate (3+) and mild (2+) in 15 and 30 days thinner
      inhalation groups, respectively. Strong staining (4+) was restored following the
      recovery period. Testicular weight was significantly reduced in all test groups
      compared to the control values (p<0.01). Diameters of seminiferous tubules were
      significantly decreased in the solvent exposed groups with enlarged connective
      tissue. The present findings suggest that paint thinner inhalation inhibits
      testosterone synthesis and secretion by a direct action on the Leydig cells in a
      reversible manner.

PMID- 16978834
TI  - Sex differences in methamphetamine-evoked striatal dopamine of mice are reversed
      by nomifensine.
AB  - Male mice show more severe striatal dopamine depletions to the psychostimulant,
      methamphetamine (MA). To gain some understanding for this sex difference, we
      examined MA-evoked dopamine (DA) responses from superfused striatal tissue
      fragments of male and female mice under conditions of a dopamine transporter
      which was either unaltered (Experiment 1) or inhibited, with use of the drug,
      nomifensine (Experiment 2). In Experiment 1, MA-evoked DA was significantly
      greater in male versus female mice. In Experiment 2, diminished, albeit
      statistically significant, DA responses to MA infusion in the presence of
      nomifensine were obtained from striatal tissue of female, but not male, mice. In
      Experiment 3, potassium-evoked DA responses and sex differences were abolished in
      the presence of nomifensine. These data demonstrate a clear sex difference in DA
      responses to MA. Interestingly, under conditions where dopamine transporter
      function is inhibited, MA retains its ability to evoke DA. However, this capacity
      was only observed within striatal tissue fragments of female mice and not under
      conditions of potassium-evoked DA. These results indicate an additional component
      for the bases of sex differences in nigrostriatal dopaminergic function in health
      and in disease. In particular, the present findings have important implications
      in suggesting an alternative, non-traditional, mechanism for MA effects and
      indicate that such a function is limited to females.

PMID- 16978835
TI  - Acoustic analyses of sustained and running voices from patients with laryngeal
      pathologies.
AB  - In this paper, we investigated the acoustic characteristics of sustained and
      running vowels from normal subjects and patients with laryngeal pathologies.
      Perturbation methods (including jitter and shimmer), signal-to-noise ratio (SNR),
      and nonlinear dynamic methods (such as correlation dimension and second-order
      entropy) were used to analyze sustained and running vowels. We found that the
      sustained vowels and running voices from normal subjects and patients with
      laryngeal pathologies had low-dimensional dynamic characteristics. For sustained
      vowels, the analyses of jitter, shimmer, correlation dimension, and second-order
      entropy revealed significant differences between normal and pathological voices.
      For running voices, jitter and shimmer did not statistically discriminate between
      normal and pathological voices, but a significant difference was found for SNR,
      correlation dimension, and second-order entropy. The results suggest that
      nonlinear dynamic analysis and traditional SNR analysis may be valuable for the
      analysis of sustained and running vowels; perturbation analysis may be applicable
      for the analysis of sustained vowels but should be applied with caution for
      running voice analysis.

PMID- 16978836
TI  - Considerations for maintenance of postural alignment for voice production.
AB  - There is general agreement that postural alignment is important in optimizing
      voice function. A number of articles have illuminated the way in which posture,
      particularly of the cervical spine, is directly related to vocal resonance and
      pitch control. Despite frequent involvement in muscle training, few speech
      pathologists have the background in exercise physiology necessary to appreciate
      the contribution of muscular length-tension relationships to postural alignment.
      The purpose of this article is to provide voice therapists with information to
      help them formulate appropriate recommendations for improving postural alignment.
      This article synthesizes information from the literature regarding the role of
      muscular length-tension balance in the attainment and maintenance of postural
      alignment. Important considerations in the assessment of muscle tension and
      weakness are presented along with advice regarding application to the treatment
      of voice-disordered patients. Concepts detailed include agonist/antagonist
      relationships, the biomechanics of stretching, postural assessment, and the
      relationship between muscle tension and muscle weakness. The role of both
      stretching and strength-based training is discussed. Specific exercises with
      emphasis on altering the alignment of the cervical and thoracic spine are
      presented with suggestions for their use in the clinic. There is growing
      understanding of the physiology behind recommendations of voice teachers and
      therapists to maintain optimal alignment. To effectively mediate postural
      misalignment, clinicians must have knowledge of the length-tension relationships
      between muscles. This understanding will lead to better interventions for
      postural alignment.

PMID- 16978837
TI  - Kinetic modeling of PET-FDG in the brain without blood sampling.
AB  - The aim in this work is to report a new method to calculate parametric images
      from a single scan acquisition with positron emission tomography (PET) and
      fluorodeoxyglucose (FDG) in the human brain without blood sampling. It is usually
      practical for research or clinical purposes to inject the patient in an isolated
      room and to start the PET acquisition only for some 10-20 min, about 30 min after
      FDG injection. In order to calculate the cerebral metabolic rates for glucose
      (CMRG), usually several blood samples are required. The proposed method considers
      the relation between the uptake of the tracer in the cerebellum as a reference
      tissue and the population based input curve. Similar results were obtained for
      CMRG values with the present method in comparison to the usual autoradiographic
      and the non-linear least squares fitting of regions of interest.

PMID- 16978838
TI  - Feedback control of MKP-1 expression by p38.
AB  - Mitogen-activated protein (MAP) kinases play a critical role in innate immune
      responses to microbial infection through eliciting the biosynthesis of
      proinflammatory cytokines. MAP phosphatases (MKP)-1 is an archetypical member of
      the dual-specificity phosphatase family that deactivates MAP kinases. Induction
      of MKP-1 has been implicated in attenuating the lipopolysaccharide (LPS) and
      Peptidoglycan (PGN) responses, but how the expression of the MKP-1 is regulated
      is still not fully understood. Here, we show that inhibition of p38 MAP kinase by
      specific inhibitor SB 203580 or RNA interference (RNAi) markedly reduced the
      expression of MKP-1 in LPS or PGN-treated macrophages, which is correlated with
      prolonged activation of p38 and JNK. Depletion of MAPKAP kinase 2 (MK2), a
      downstream substrate of p38, by RNAi also inhibited the expression of MKP-1. The
      mRNA level of MKP-1 is not affected by inhibition of p38, but the expression of
      MKP-1 is inhibited by treatment of cycloheximide. Thus, p38 MAPK plays a critical
      role in mediating expression of MKP-1 at a post-transcriptional level.
      Furthermore, inhibition of p38 by SB 203580 prevented the expression of MKP-1 in
      LPS-tolerized macrophages, restored the activation of MAP kinases after LPS
      restimulation. These results indicate a critical role of p38-MK2-dependent
      induction of MKP-1 in innate immune responses.

PMID- 16978839
TI  - Neuregulin-1 only induces trans-phosphorylation between ErbB receptor heterodimer
      partners.
AB  - ErbB2, ErbB3 and ErbB4 are members of the Epidermal Growth Factor Receptor (EGFR)
      sub-family of Receptor Tyrosine Kinases (RTKs). Neuregulin-1 (NRG-1) is a ligand
      of ErbB3 and ErbB4 receptors. NRG-1-induced ErbB2/ErbB3 or ErbB2/ErbB4
      heterodimerization, followed by receptor phosphorylation, plays multiple
      biological roles. To precisely determine the phosphorylation status of each ErbB
      receptor in ErbB2/ErbB3 and ErbB2/ErbB4 heterodimers, an immunoprecipitation
      recapture of the ErbB receptors was performed to exclude any co
      immunoprecipitated heterodimer partners from cells with co-expression of
      ErbB2/ErbB3, ErbB2/ErbB4, or ErbB2/ErbB4D843N, a kinase-inactive ErbB4 mutant, in
      which the aspartic acid at 843 (D843) was replaced by an asparagine (N). Here, we
      provide direct biochemical evidence that ErbB2 was only trans-phosphorylated by
      ErbB4, but not by ErbB3 or ErbB4D843N. By contrast, ErbB3, ErbB4 and ErbB4D843N
      were trans-phosphorylated by ErbB2 in the co-transfected cells. Therefore, we
      conclude that trans-phosphorylation, but not cis-phosphorylation occurred between
      ErbB2/ErbB3 and ErbB2/ErbB4 heterodimer partners by NRG-1 stimulation.

PMID- 16978840
TI  - Interaction of PLD1b with actin in antigen-stimulated mast cells.
AB  - Phosphatidic acid, the product of phospholipase D catalysed phosphatidylcholine
      hydrolysis is an important signalling molecule that has been implicated in
      regulation of actin cytoskeleton remodelling and secretion from mast cells. We
      show that human PLD1b (hPLD1b) is an actin-binding protein and the N-terminus is
      predominantly involved in this interaction. Protein kinase C (PKC) is a major
      upstream regulator of PLD activity and PKC phosphorylation sites have been
      identified within the N-terminus of PLD1b at serine 2 and threonine 147. Over
      expression of wild type hPLD1b in mast cells showed that antigen stimulation
      significantly enhanced co-localisation of PLD1b with actin structures. Mutation
      of serine 2 to alanine abolished antigen-induced co-localisation whereas mutation
      of threonine 147 had less dramatic effects on co-localisation. The absence of co
      localisation of PLD1b (S2A) with actin coincides with a significant decrease in
      PLD activity in cells expressing the PLD1b (S2A) mutant. In resting RBL-2H3
      cells, mutation of serine 2 to aspartate resulted in constitutive co-localisation
      of PLD with the actin cytoskeleton, coincident with restored PLD activity. These
      results reveal that serine 2 is an important regulatory site involved in
      controlling PLD enzyme activity and the interaction between PLD and actin.

PMID- 16978841
TI  - TNF family molecule LIGHT regulates chemokine CCL27 expression on mouse embryonic
      stem cell-derived dendritic cells through NF-kappaB activation.
AB  - Cytokine LIGHT is a type II transmembrane protein belonging to the TNF family
      that was originally identified as a weak inducer of apoptosis. It plays a role in
      inducing maturation of dendritic cells, such as upregulating CD80, CD86
      expression on dendritic cells. However, whether LIGHT induces CC chemokine
      expression in DC and promotes their migration remains unknown. In this study, we
      found that esDC express CCR7 and CCR10 (the receptor of CCL27) upon the LIGHT
      stimulation. LIGHT also upregulates CCL27, but not CCL19 and CCL21 expression in
      esDC. The esDC migration potential has been increased in LIGHT activated DCs
      compared with control cells. LIGHT activated DCs autocrine CCL27 which regulate
      their migration as Blockage of CCL27 on esDC using neutralizing antibody reduces
      migration potential. In signaling study, we identified that LIGHT activated NF
      kappaB in esDC and inhibition of NF-kappaB activation by specific inhibitor can
      partly attenuate the effect of LIGHT in regulation of CCL27 expression. Moreover,
      Shp-2 is required in LIGHT activated NF-kappaB because Knockdown of Shp-2 affects
      the NF-kappaB activation induced by LIGHT and consequently influences LIGHT
      mediated CCL27 expression. TRAF6 is critical in DC maturation in recent reports;
      however, knockdown of TRAF6 expression using siRNA did not alter CCL27 expression
      in LIGHT matured DCs. Our study demonstrates that LIGHT stimulation enhances
      CCL27 expression through activation of NF-kappaB in DCs.

PMID- 16978843
TI  - Nutritional profile of the Brazilian Amputee Soccer Team during the
      precompetition period for the world championship.
AB  - OBJECTIVE: The purpose of this study was to determine the dietary and
      anthropometric profiles of the Brazilian amputee soccer players during the
      training period before the world soccer amputee championship, according to their
      positional roles in the game. METHODS: Fifteen male athletes participated in the
      study. Data on height, weight, skinfold thickness, and circumferences were
      collected to assess nutritional status. Dietary intake was obtained by using 6-d
      dietary records, analyzed by a Nutrition Support Program for total energy intake,
      carbohydrates, proteins, lipids, vitamins, and minerals. One-way analysis of
      variance was used to identify differences in groups (P < 0.05). RESULTS: Midfield
      players were heavier than the others, and this difference may have been caused by
      a large quantity of subcutaneous fat. Dietary data showed a low carbohydrate
      intake and high protein and fat intakes. No athlete met the recommendations for
      vitamin E, and forward players did not meet recommendations for calcium.
      CONCLUSION: Amputee athletes need an individualized nutritional orientation and
      the lack of information about disabled sports and athletes highlights the need
      for more studies in this area.

PMID- 16978842
TI  - The bioactive lipid sphingosylphosphorylcholine induces differentiation of mouse
      embryonic stem cells and human promyelocytic leukaemia cells.
AB  - Sphingosylphosphorylcholine (SPC) is the major component of high-density
      lipoproteins (HDL) in blood plasma. The bioactive lipid acts mainly via G protein
      coupled receptors (GPCRs). Similar to ligands of other GPCRs, SPC has multiple
      biological roles including the regulation of proliferation, migration,
      angiogenesis, wound healing and heart rate. Lysophospholipids and their receptors
      have also been implicated in cell differentiation. A potential role of SPC in
      stem cell or tumour cell differentiation has been elusive so far. Here we
      examined the effect of SPC on the differentiation of mouse embryonic stem (ES)
      cells and of human NB4 promyelocytic leukemia cells, a well established tumour
      differentiation model. Our data show that mouse embryonic stem cells and NB4
      cells express the relevant GPCRs for SPC. We demonstrate both at the level of
      morphology and of gene expression that SPC induces neuronal and cardiac
      differentiation of mouse ES cells. Furthermore, SPC induces differentiation of
      NB4 cells by a mechanism which is critically dependent on the activity of the MEK
      ERK cascade. Thus, the bioactive lipid SPC is a novel differentiation inducing
      agent both for mouse ES cells, but also of certain human tumour cells.

PMID- 16978844
TI  - Effect of a probiotic food as an adjuvant to triple therapy for eradication of
      Helicobacter pylori infection in children.
AB  - OBJECTIVE: Current recommendations for treatment of Helicobacter pylori infection
      include a proton pump inhibitor in combination with two antibiotics. We evaluated
      the potential activity of a probiotic food as an adjuvant to antibiotic triple
      therapy for eradication of H. pylori infection in children from Buenos Aires,
      Argentina. METHODS: Sixty-five children who tested positive for H. pylori, as
      diagnosed by (13)C-urea breath test and endoscopy, were included in this study.
      Patients were randomized to receive 1-wk triple therapy plus probiotic food
      (treated group) or milk placebo (control) that was administered for 3 mo.
      Probiotic food consisted of 250 mL of a commercial yogurt containing
      Bifidobacterium animalis and Lactobacillus casei (10(7) colony-forming units/mL).
      Post-treatment urea breath test controls were performed 1 and 3 mo after the end
      of triple therapy. RESULTS: We found no significant differences in H. pylori
      eradication rates (ERs) at 1 and 3 mo between the treated group (ER = 45.5% and
      42.4%) and the control group (ER = 37.5% and 40.6%). Relative risks between
      groups were 0.87 (95% confidence interval 0.58-1.32, P = 0.345) in the first
      month and 0.97 (95% confidence interval 0.64-1.46, P = 0.542) in the third month.
      CONCLUSIONS: We could not demonstrate an adjuvant effect of the studied probiotic
      food to triple therapy in the eradication of H. pylori infection in children in
      Buenos Aires, Argentina. However, we found lower ERs than those reported for the
      same therapeutic scheme in developed countries, indicating that bacterial
      resistance and alternative therapeutic strategies should be studied.

PMID- 16978845
TI  - Complex regulation of mucosal pentraxin (Mptx) revealed by discrete micro
      anatomical locations in colon.
AB  - Recently a mucosal pentraxin, Mptx, regulated by heme and calcium was reported in
      rat gut mucosal scrapings using microarray strategies. Considering the
      heterogeneity of gut mucosa scrapings and the widespread use of the rat as a
      model to study colon pathologies this study was undertaken to generate detailed
      mapping of micro-anatomical locations of Mptx and gain further insight into
      potential functions of this mucosal pentraxin in rat colon. Differential
      regulation was also examined in colon from different rat strains and rat models
      of oxidative stress and in pre-cancerous colon tissue. Different regional
      patterns of expression and discrete localisation in epithelial cells within
      transverse and distal colon crypts and an absence of expression in proximal colon
      were confirmed by regional PCR analysis and in situ hybridisation studies of
      colon. This study demonstrates that consideration of regional differences in Mptx
      gene expression and micro-anatomical location is necessary in the interpretation
      and deciphering of its regulation in colon.

PMID- 16978846
TI  - Theoretical analysis and verification of concentration distribution model in the
      ultrafiltration process.
AB  - Based on the assumed flat model, Navier-Stokes equation for two-dimensional
      laminar flow fluid and the theory for diffusion and mass transfer, we obtained
      theoretical results with regarding to the concentration distribution in
      separation process by mass transfer model in the ultrafiltration process. Through
      theoretical analysis and experimental verification of concentration distribution,
      it was known that this model could not only preferably describe the concentration
      distribution of ultrafiltration process but also forecast concentration
      polarization phenomenon.

PMID- 16978847
TI  - Single particle friction on blister packaging materials used in dry powder
      inhalers.
AB  - Using atomic force microscopy (AFM) the adhesion and sliding friction behaviour
      of single lactose particles attached directly to AFM cantilevers has been
      studied. Measurements were made on the two sides of a blister packaging material
      used in dry powder inhalers (DPI). Although no significant differences in
      adhesion were observed, clear differences in particle friction were evident,
      where one side offers consistently greater friction across the range of loads
      studied here. The packaging samples were characterised by time-of-flight
      secondary ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy
      (XPS) and found to have different surface chemistries. The observed difference in
      friction behaviour is discussed in the context of the differences seen in surface
      chemistry, topography and hardness. It is reasoned that in this case hardness has
      the largest influence, and on one sample soft surface layers are displaced by the
      particle. A clear relationship between friction and load was only observed with
      one of the three particles tested; this was attributed to multiple asperities
      being brought into contact, illustrating the important role of nanoscale contact
      geometry in determining friction behaviour.

PMID- 16978848
TI  - In vitro study of lysozyme in poly(lactide-co-glycolide) microspheres with
      sucrose acetate isobutyrate.
AB  - This study investigated the suitability of microsphere formulations for extended
      protein delivery and complete protein release. These microspheres were prepared
      by a multi-emulsion method and prepared using a mixture of poly(lactide-co
      glycolide) (PLGA), RG 502H (lactide:glycolide=50:50, M(W) 9300) and sucrose
      acetate isobutyrate (SAIB). SAIB embedded into the microspheres and mixed with
      PLGA, improved the efficiency of enzyme encapsulation. The in vitro release rate
      of lysozyme (Lys) from the microspheres was reduced due to the high viscosity of
      the added SAIB and less degradation of PLGA by SAIB. These properties enabled
      prolonged release of Lys for up to 2 months, characterized by a minimal initial
      burst of Lys and nearly zero-order protein release kinetics result from co
      administration of sorbitan monooleate 80. When it is considered that degradation
      products of SAIB are inactive for labile proteins, SAIB may be regarded as a
      promising candidate for long-acting protein delivery.

PMID- 16978849
TI  - [Non-invasive ventilation in infants with severe infection presumably due to
      respiratory syncytial virus: feasibility and failure criteria].
AB  - Beneficial effect of continuous positive airway pressure (CPAP) during non
      invasive ventilation (NIV) has been reported in infants with respiratory
      syncytial virus (RSV) infection, but no study has analyzed the predictors of its
      failure. OBJECTIVE: To evaluate the feasibility of NIV and to determine NIV
      failure criteria. POPULATION AND METHODS: All infants hospitalized in one PICU
      with presumed RSV infection between 2002 and 2006 were prospectively included.
      When respiratory support was needed, NIV was first started according to a pre
      established protocol. RESULTS: One hundred and one infants, 43 females, 58 males,
      median age 49 days (range: 10-334), median weight 3.9 kg (range: 2,4-12) were
      included. RSV infection was confirmed in 84/101. Sixty-seven infants were
      transported by the paediatric medical transport system, 27 with NIV and 15 with
      invasive ventilation (IV). Fifteen infants were in IV at admission, 69 received
      NIV during their PICU stay (12 secondarily requiring IV) and 17 were never
      ventilated. A significant decrease in PCO2 with increase in pH was observed
      within 2 hours of NIV. Parameters associated with NIV failure were apneas, high
      values of admission PCO2 and H24 PRISM score. The 17 non-ventilated infants were
      older and had a lower severity score than those who were ventilated. CONCLUSION:
      In infants with RSV and needing respiratory support, NIV represented the sole
      method of respiratory support in 68% of cases. NIV failure criteria were apneas,
      high values of admission PCO2 and H24 PRISM score.

PMID- 16978850
TI  - Sexual size dimorphism in a Drosophila clade, the D. obscura group.
AB  - The Drosophila obscura clade consists of about 41 species, of which 20 were used
      for analyses of wing and thorax length. Our primary goal was to investigate the
      magnitude of sexual size dimorphism (SSD) of these traits within this clade and
      to test Rensch's Rule [when females are larger than males, SSD (e.g., female/male
      ratio) should decrease with body size]. Our secondary goal was methodological and
      involved evaluating for these flies alternative measures of SSD (female/male
      ratio, female/male absolute difference, female/male relative difference),
      developing a bootstrap method to estimate the magnitude of intraspecific
      variation in SSD, and applying a new method of estimating allometric
      relationships that is phylogenetically based and incorporates error variance in
      both traits. All indices of SSD were strongly correlated for both size traits.
      Nevertheless, female/male ratio is the best index here: it is easily
      interpretable and essentially independent of size. For both traits, SSD (F/M)
      varied interspecifically, showed a strong phylogenetic signal, but did not differ
      for the main phylogenetic subgroups or correlate with latitude. Factors
      underlying variation in SSD in this clade are elusive and might include genetic
      drift. SSD (wing) tended to decrease with increasing size, as predicted by
      Rensch's Rule, though not consistently so. SSD (thorax) was unrelated to size.
      However, analysis of published data for thorax length of Drosophila spp. (N=42)
      with a larger size range showed that SSD decreased significantly with increasing
      size (consistent with Rensch's Rule), suggesting our ability to detect SSD-size
      relations in the D. obscura data may be limited by low statistical power.

PMID- 16978851
TI  - Phytotherapy for functional dyspepsia: a review of the clinical evidence for the
      herbal preparation STW 5.
AB  - Functional gastrointestinal disorders such as functional (or non-ulcer) dyspepsia
      are characterized by a broad spectrum of symptoms referred to the upper abdomen
      without a detectable cause utilizing routine diagnostic measures. It is now
      believed that disordered gut function (including abnormalities like disturbances
      of motility such as postprandial fundic relaxation, gastric emptying and
      disturbed visceral sensory function) play a key role for the manifestation of
      these disorders. The underlying pathophysiology is not yet fully understood.
      However, the available data suggest that a number of factors may contribute to
      the manifestation of symptoms. These factors include environmental factors such
      as acute infections as trigger event, psychological stressors that may precede
      acute exacerbations and a genetic predisposition. Considering the large number of
      mechanisms, a treatment targeting a single mechanism is unlikely to be effective
      in all patients. Indeed, chemically defined treatments usually gain a 10-15%
      superiority over placebo. In recent years placebo-controlled studies have
      demonstrated superiority of a commercial multicomponent herbal preparation, STW
      5, with the trade name Iberogast, for the treatment of patients with functional
      dyspepsia and irritable bowel syndrome. This phytopharmacon is a combination of
      nine plant extracts each with a number of different active constituents.
      Pharmacological studies have shown different effects of the single plant extracts
      on the (molecular) mechanisms which are discussed as underlying the manifestation
      of symptoms. Various well-controlled clinical trials have independently confirmed
      clinical efficacy and safety. The clinically efficacy of this multicomponent
      herbal preparation questions the current trend of highly targeted drug molecules
      that usually target one single receptor population while it has not been shown
      that a single receptor group plays a pivotal role for the control of symptoms.
      Herbal medicines are obtained from various plants and contain complex extracts
      with a large number of different active substances. While there are only limited
      head-to-head comparisons with conventional chemically defined medications, the
      combination of extracts with various gastrointestinal active ingredients appears
      to be advantageous for a heterogeneous condition such as functional dyspepsia.

PMID- 16978852
TI  - Spasmolytic and tonic effect of Iberogast (STW 5) in intestinal smooth muscle.
AB  - STW 5 (Iberogast) is a fixed combination of nine medicinal plant extracts
      effective in the treatment of functional dyspepsia and irritable bowel syndrome.
      The effects of STW 5, a combination of Iberis amara fresh plant extract, and
      other eight plant extracts as well as single extract components including
      extracts from Menthae piperitae folium, Matricariae flos and Liquiritiae radix,
      were assayed in guinea pig ileum with or without stimulation with acetylcholine
      or histamine, in order to find a possible effect on the contractility of
      intestinal smooth muscle. STW 5 decreased acetylcholine- and histamine-induced
      contraction of guinea pig ileum. This was also true for extracts of Menthae
      piperitae folium, Matricariae flos and L. radix. Extract from I. amara, however,
      showed no spasmolytic action; in contrary, it increased the basal resting tone
      and contraction of atonic ileal segments. This was also true when STW 5 was
      employed. A spasmolytic action of STW 5 could also be observed in duodenum,
      jejunum and colon. These data are the first to show not only the spasmolytic
      effects of STW 5 and its component extracts in intestinal muscle but also the
      tonicising effects of STW 5 through its component Iberis amara extract in relaxed
      intestinal muscle. Thus, pharmacological evidence suggests a dual-action
      principle and may explain, at least in part, the clinically observed therapeutic
      efficacy of STW 5 (Iberogast) in both hypotonic and spastic dysmotility symptoms
      of functional dyspepsia and irritable bowel syndrome.

PMID- 16978853
TI  - Integrated reverse transcription polymerase chain reaction systems for virus
      detection.
AB  - The current study reports on an integrated microreverse transcription polymerase
      chain reaction (RT-PCR) system for molecular diagnosis of microorganisms
      automatically. By using antibodies-conjugated superparamagnetic beads, the
      developed system can detect viruses with higher sensitivity and specificity when
      compared with traditional biological diagnosis methods using a ribonucleic acid
      (RNA) extraction kit. The target viruses were first captured by the conjugated
      antibodies on the magnetic beads, and were enriched using a magnetic field
      generated by micro-electromagnets or permanent magnets. With this approach, the
      virus can be purified and concentrated first, then the virus RNA was extracted
      and transcripted to complementary deoxyribonucleic acid (cDNA), followed by a
      nucleic acid amplification process using a micro-RT-PCR module. The integrated
      microfluidic chip can perform the whole process automatically with the aid of
      integrated micropumps and microvalves. This study successfully performs the
      specific detection of two different types of viruses, Dengue virus serotype 2 and
      enterovirus (EV) 71 using this developed integrated system. Comparable to a large
      scale apparatus, the integrated microsystem can perform mixing, incubation,
      purification, transportation, and nucleic acid amplification of virus, possibly
      making it a crucial platform for future diagnosis applications.

PMID- 16978855
TI  - Essential genes on metabolic maps.
AB  - Within the past five years genome-scale gene essentiality data sets have been
      published for ten diverse bacterial species. These data are a rich source of
      information about cellular networks that we are only beginning to explore. The
      analysis of these data, very heterogeneous in nature, is a challenging task. Even
      the definition of 'essential genes' in various genome-scale studies varies from
      genes 'absolutely required for survival' to those 'strongly contributing to
      fitness' and robust competitive growth. A comparative analysis of gene
      essentiality across multiple organisms based on projection of experimentally
      observed essential genes to functional roles in a collection of metabolic
      pathways and subsystems is emerging as a powerful tool of systems biology.

PMID- 16978854
TI  - New metrics for comparative genomics.
AB  - The availability of genome sequences from a variety of organisms presents an
      opportunity to apply this sequence information to solving the key problems of
      molecular biology. One of the principal roadblocks on this path is the lack of
      appropriate descriptors and metrics that could succinctly represent the new
      knowledge stemming from the genomic data. Several new metrics have recently been
      used in comparative genome analysis, yet challenges remain in finding an
      appropriate language for the emerging discipline of systems biology.

PMID- 16978857
TI  - Engineering tissues for in vitro applications.
AB  - Engineered tissues can be employed for studies on the fundamental mechanisms of
      embryology and adult physiology and for investigating the evolution of disease
      processes. They also provide platforms to evaluate the behavior of new chemical
      entities in drug development. The recent development of three specific
      technologies has greatly facilitated the engineering of tissues for in vitro
      applications: the microfabrication tools that serve to both define the cellular
      microenvironment and enable parallelization of cell-based assays; synthetic,
      tunable hydrogels to create three-dimensional microenvironments; and bioreactors
      to control nutrient transport and fluid shear stress. Furthermore, convergence of
      these tools is providing investigators with the opportunity to construct and
      study tissues in vitro with unprecedented levels of sophistication.

PMID- 16978856
TI  - Genetic parts to program bacteria.
AB  - Genetic engineering is entering a new era, where microorganisms can be programmed
      using synthetic constructs of DNA encoding logic and operational commands. A
      toolbox of modular genetic parts is being developed, comprised of cell-based
      environmental sensors and genetic circuits. Systems have already been designed to
      be interconnected with each other and interfaced with the control of cellular
      processes. Engineering theory will provide a predictive framework to design
      operational multicomponent systems. On the basis of these developments,
      increasingly complex cellular machines are being constructed to build specialty
      chemicals, weave biomaterials, and to deliver therapeutics.

PMID- 16978860
TI  - The relevance of RT-PCR detection of disseminated tumour cells is hampered by the
      expression of markers regarded as tumour-specific in activated lymphocytes.
AB  - Marker genes, commonly used to detect circulating tumour cells in RT-PCR-based
      tests: squamous-cell carcinoma antigen, epidermal growth factor receptor,
      mammaglobin, small breast epithelial mucin, but not carbonic anhydrase 9, were
      shown to be expressed in normal, mitogen-stimulated peripheral blood mononuclear
      cells (PBMNC). Thus, considering the inflammatory reactions often accompanying
      cancer development, to reduce false-positive results of the metastatic tumour
      cell tests, molecular markers should be validated not against normal peripheral
      blood, but against activated lymphoid cells, such as in vitro mitogen-stimulated
      PBMNC.

PMID- 16978861
TI  - Childhood acute myelogenous leukaemia: association between PRAME, apoptosis- and
      MDR-related gene expression.
AB  - The gene PRAME (preferentially expressed antigen of melanoma) encodes an antigen
      recognised by autologous cytolytic T lymphocytes. The mRNA level of PRAME is used
      as a tumour marker due to its overexpression in various malignancies.
      Furthermore, it is known that the overexpression of genes encoding antiapoptotic
      proteins leads to the survival of leukaemic cells via exclusion of apoptosis. On
      the other hand, overexpression of genes encoding ABC transporters may lead to
      multi drug resistance (MDR). Therefore, we investigated whether there is a
      relationship between PRAME overexpression and the expression of apoptosis- and
      MDR-related genes in childhood de novo acute myelogenous leukaemia (AML) patient
      samples and, furthermore, whether this is a general or an AML-subtype specific
      event. Microarray analysis and real time quantitative PCR revealed that clinical
      samples showing PRAME upregulation are associated with a decreasing expression of
      genes coding for apoptotic proteins and an overexpression of genes encoding ABC
      transporters. Our results indicate that patients showing PRAME upregulation may
      have an increased risk of MDR induction.

PMID- 16978862
TI  - Synthesis of 1,2,4-trioxepanes via application of thiol-olefin co-oxygenation
      methodology.
AB  - Thiol-olefin co-oxygenation (TOCO) of substituted allylic alcohols generates beta
      hydroxy peroxides that can be condensed in situ with various ketones, to afford a
      series of functionalised 1,2,4-trioxepanes in good yields. Manipulation of the
      phenylsulfenyl group in 8a-8c allows for convenient modification to the spiro
      trioxepane substituents. Surprisingly, and in contrast to the 1,2,4-trioxanes
      examined, 1,2,4-trioxepanes are inactive as antimalarials up to 1000 nM and we
      rationalize this observation based on the inherent stability of these systems to
      ferrous mediated degradation. FMO calculations clearly show that the sigma*
      orbital of the peroxide moiety of 1,2,4-trioxane derivatives 4a and 14b are lower
      in energy and more accessible to attack by Fe(II) compared to their trioxepane
      analogues 8b and 9b.

PMID- 16978863
TI  - 3-(Indol-2-yl)indazoles as Chek1 kinase inhibitors: Optimization of potency and
      selectivity via substitution at C6.
AB  - The development of 3-(indol-2-yl)indazoles as inhibitors of Chek1 kinase is
      described. Introduction of amides and heteroaryl groups at the C6 position of the
      indazole ring system provided sufficient Chek1 potency and selectivity over Cdk7
      to permit escape from DNA damage-induced arrest in a cellular assay. Enzyme
      potency against Chek1 was optimized by the incorporation of a hydroxymethyl
      triazole moiety in compound 21 (Chek1 IC(50)=0.30nM) that was shown by X-ray
      crystallography to displace one of three highly conserved water molecules in the
      HI region of the ATP-binding cleft.

PMID- 16978864
TI  - Synthesis and antihyperlipidemic activity of novel glycosyl fructose derivatives.
AB  - A series of novel di and trisaccharide derivatives containing d-fructose moiety
      at the reducing end have been synthesized and evaluated for their
      antihyperlipidemic activity in hyperlipidemic hamster model. Among 11 glycosyl
      fructose derivatives five compounds showed potent antihyperlipidemic activity
      either by enhancing high-density lipoprotein (HDL) cholesterol concentration
      and/or lowering triglyceride (TG) level.

PMID- 16978866
TI  - Traumatic oculomotor nerve palsy.
AB  - Traumatic isolated oculomotor nerve palsy is not common. Oculomotor nerve palsy
      without internal ophthalmoplegia (pupil sparing) is extremely rare. We report a
      case of this condition in a child. An 11-year-old boy was transferred to our
      hospital after a head injury in a traffic accident. Neuro-ophthalmic examination
      showed that the left eye had limited adduction, supraduction, and infraduction,
      incomplete convergence and left ptosis, but no internal ophthalmoplegia. Magnetic
      resonance imaging indicated mild bending of the ipsilateral oculomotor nerve at
      the posterior petroclinoid ligament. One month after injury, movement of the
      patient's eyes was normal on examination, but there was mild diplopia. The
      suggested mechanism of the oculomotor nerve palsy with pupil sparing in this case
      is stretching of the oculomotor nerve at the posterior petroclinoid ligament,
      maintaining an intact pupillomotor nerve.

PMID- 16978865
TI  - CRACM1 multimers form the ion-selective pore of the CRAC channel.
AB  - Receptor-mediated Ca(2+) release from the endoplasmic reticulum (ER) is often
      followed by Ca(2+) entry through Ca(2+)-release-activated Ca(2+) (CRAC) channels
      in the plasma membrane . RNAi screens have identified STIM1 as the putative ER
      Ca(2+) sensor and CRACM1 (Orai1; ) as the putative store-operated Ca(2+) channel.
      Overexpression of both proteins is required to reconstitute CRAC currents
      (I(CRAC); ). We show here that CRACM1 forms multimeric assemblies that bind STIM1
      and that acidic residues in the transmembrane (TM) and extracellular domains of
      CRACM1 contribute to the ionic selectivity of the CRAC-channel pore. Replacement
      of the conserved glutamate in position 106 of the first TM domain of CRACM1 with
      glutamine (E106Q) acts as a dominant-negative protein, and substitution with
      aspartate (E106D) enhances Na(+), Ba(2+), and Sr(2+) permeation relative to
      Ca(2+). Mutating E190Q in TM3 also affects channel selectivity, suggesting that
      glutamate residues in both TM1 and TM3 face the lumen of the pore. Furthermore,
      mutating a putative Ca(2+) binding site in the first extracellular loop of CRACM1
      (D110/112A) enhances monovalent cation permeation, suggesting that these residues
      too contribute to the coordination of Ca(2+) ions to the pore. Our data provide
      unequivocal evidence that CRACM1 multimers form the Ca(2+)-selective CRAC-channel
      pore.

PMID- 16978867
TI  - Analysis of synaptic bodies in the Sprague-Dawley rat pineal gland under extreme
      photoperiods.
AB  - Synaptic bodies (SBs) are small, prominent organelles in pinealocytes, most
      probably involved in signal transduction processes. To check the influence of the
      photoperiod on their shape plasticity and number we chose two extreme lighting
      conditions, i.e. 20h of illumination followed by 4h of darkness (LD 20:4) versus
      (LD 4:20). Pineal glands were assessed at 0, 4 and 13h after dark onset. Under
      both conditions reconstructed SBs were plates or ribbons but never spheres and
      there were no obvious differences in morphology. Photoperiodic changes in SB
      profile size and number were investigated: application of the established method
      for SB quantification based on single section profile counts (SSPC) of areas
      showed a significant increase of SB profiles under LD 20:4. However, it has to be
      noted that SSPC depend on both, number and size of the structures. In contrast to
      this, modification of the disector counting method, also applied for unbiased
      quantification of whole SBs, revealed that rat pinealocytes show insignificantly
      more SBs under LD 20:4 than under 4:20 conditions. The lengths of the SB
      profiles, which were first measured under different conditions in this study,
      depend on SB size. They increased significantly under LD 20:4. In conclusion, we
      detected only an increase in SB size but not in their number. We further prove
      that, at least for SBs, it is of no value to calculate disector levels from
      SSPCs.

PMID- 16978868
TI  - Sensilla of the antenna and palp of Hydrotaea chalcogaster (Diptera: Muscidae).
AB  - Hydrotaea chalcogaster is a fly species of medical and forensic importance in
      many parts of the world. In this study, we investigated the sensilla of the
      antenna and palp of the adult female fly using scanning electron microscopy. The
      antennal scape has one type of sensillum, the sharp-tipped sensillum trichodeum;
      whereas, the antennal pedicel also possessed this type of sensillum in addition
      to an unidentified type. Three types of sensilla were found on the flagellum: (1)
      sensilla basiconica, with both large and small sensilla basiconica showing wall
      pores, (2) sensilla coeloconica, with a smooth surface, and (3) sensory pits,
      with wall pores of pegs. The arista is located dorso-laterally on the flagellum
      and has three segments. Short microtrichia are located around the distal end of
      its second segment and on the proximal half of the third segment. Both large
      sharp-tipped sensilla chaetica and small sensilla basiconica with wall pores were
      observed on the palps. Results of this study contribute to our overall
      understanding of the ultrastructural morphology of sensilla on the antenna and
      palp of H. chalcogaster.

PMID- 16978869
TI  - Pyruvate protects cerebellar granular cells from 6-hydroxydopamine-induced
      cytotoxicity by activating the Akt signaling pathway and increasing glutathione
      peroxidase expression.
AB  - Parkinson disease (PD) is the second-most common age-related neurodegenerative
      disease and is characterized by the selective destruction of dopaminergic
      neurons. Increasing evidence indicates that oxidative stress plays a crucial role
      in the pathogenesis of idiopathic PD. Anti-oxidant agents including catalase,
      manganese porphyrin and pyruvate confer cytoprotection to different cell cultures
      when challenged with 6-hydroxydopamine (6-OHDA). Herein we used rat cerebellar
      granular cell cultures to ascertain the plausible cellular pathways involved in
      pyruvate-induced cytoprotection against 0.1 mM 6-OHDA. Pyruvate provided
      cytoprotection in a concentration-dependent manner (2-10 mM). Consistent with its
      well-established anti-oxidant capacity, pyruvate (10 mM) prevented 6-OHDA-induced
      lipid peroxidation by blocking the rise in intracellular peroxides and
      maintaining the intracellular reduced glutathione (GSH) levels. Further
      experiments revealed that pyruvate increased Akt, but not extracellular signal
      regulated kinase phosphorylation. Moreover, phosphatidylinositol 3-kinase (PI3K)
      inhibitors attenuated pyruvate-induced cytoprotection indicating that PI3K
      mediated Akt activation is necessary for pyruvate to induce cytoprotection. On
      the other hand, pyruvate also up-regulated glutathione peroxidase mRNA levels,
      but not those of the anti-oxidant enzymes superoxide dismutase-1 and -2, catalase
      or the anti-apoptotic oncogenes Bcl-2 or Bcl-xL. In summary, our results strongly
      suggest that pyruvate, besides the anti-oxidant properties related to its
      structure, exerts cytoprotective actions by activating different anti-apoptotic
      routes that include gene regulation and Akt pathway activation.

PMID- 16978871
TI  - Left ventricular reconstruction for dilated ischemic cardiomyopathy: Biology,
      registry, randomization, and credibility.

PMID- 16978870
TI  - Genetic interaction between expanded murine Hdh alleles and p53 reveal
      deleterious effects of p53 on Huntington's disease pathogenesis.
AB  - Huntingtin, the protein product of the Huntington's disease (HD) gene, is known
      to interact with the tumor suppressor p53. It has recently been shown that
      activation of p53 upregulates the level of huntingtin, both in vitro and in vivo,
      whereas p53 deficiency in HD-transgenic flies and mice has been found to be
      beneficial. To explore further the involvement of p53 in HD pathogenesis, we
      generated mice homozygous for a mutant allele of Hdh (HdhQ140) and with zero,
      one, or two functional alleles of p53. p53 deficiency resulted in a reduction of
      mutant huntingtin expression in brain and testis, an increase in proenkephalin
      mRNA expression and a significant increase in nuclear aggregate formation in the
      striatum. Because aggregation of mutant huntingtin is suggested to be a
      protective mechanism, both the increase in aggregate load and the restoration of
      proenkephalin expression suggest a functional rescue of at least several aspects
      of the HD phenotype by a deficiency in p53.

PMID- 16978872
TI  - Chemically modified tetracyclines inhibit VEGF secretion by breast cancer cell
      lines.
AB  - Chemically Modified Tetracyclines (CMTs) are antiproteolytic agents that have
      been shown to inhibit tumor invasiveness and metastasis. CMT 300 has shown
      promise in phase I clinical trials in patients with Kaposi's Sarcoma, which is
      characterized by over-production of the pro-angiogenic cytokine vascular
      endothelial growth factor (VEGF). In this study, we report a novel activity of
      CMT 308, a 9-amino derivative of CMT 300, on reducing levels of VEGF secreted by
      breast cancer cell lines. CMT 308, at sub-cytotoxic concentrations, reduced basal
      levels of secreted VEGF in the poorly invasive MCF-7 cell line as well as the
      more aggressively invasive MDA-MB-435s cell line in a dose-dependent manner. In
      addition, CMT 308 also reduced transforming growth factor beta (TGFbeta)-induced
      VEGF secretion in both cell lines. While VEGF could be detected in the
      conditioned media of untreated MCF-7 cells within 4h, levels of secreted VEGF in
      CMT 308-treated cells remained undetectable up to 8h. CMT 308 diminished
      secretion of VEGF from MCF-7 cells up to 8h regardless of previous time in
      culture. CMT 308 did not reduce the levels of basal VEGF mRNA in either cell
      line, but did reduce pools of total intracellular VEGF protein. Although TGFbeta
      stimulated an increase in VEGF levels in the conditioned media as well as in the
      cytoplasm, TGFbeta treatment did not increase VEGF mRNA levels. Thus, augmented
      expression of VEGF protein by breast cancer cell lines in the presence of TGFbeta
      appears to involve upregulation at a step beyond transcription. Moreover, the
      data strongly indicate that in these breast cancer cell lines, CMT 308 reduces
      VEGF secretion by targeting some post-transcriptional event. The capacity of CMT
      308 to diminish levels of a major pro-angiogenic signal makes the
      nonantimicrobial tetracycline derivative an attractive candidate for anti
      angiogenic therapy in management of breast cancer.

PMID- 16978873
TI  - A systematic and efficient method to estimate the vibrational frequencies of
      linear peptide and protein ions with any amino acid sequence for the calculation
      of Rice-Ramsperger-Kassel-Marcus rate constant.
AB  - A systematic method to automatically estimate the vibrational frequency sets of
      linear peptide and protein ions with any amino acid sequence, which is needed in
      Rice-Ramsperger-Kassel-Marcus (RRKM) calculations for dissociation of these ions,
      has been developed. The method starts from the frequencies of free amino acids
      calculated quantum chemically at the DFT/B3LYP/6-31G** level. Some of these were
      systematically eliminated to get fictitious sets of frequencies for each amino
      acid at the C-terminus, N-terminus, and inside the chain. By collecting these
      sets as needed for a specified amino acid sequence and adding vibrations
      appearing upon peptide bond formation and protonation, a complete set of
      vibrational frequencies was obtained. Other conditions for RRKM calculations have
      also been systematically specified. RRKM calculations performed under various
      conditions have shown that the present method can be useful for an order of
      magnitude estimation of a statistical rate constant even at low internal energy
      region. The fact that arbitrariness involved in constructing an entire frequency
      set simply through spectral correlation can be avoided, and that any protein ion
      can be handled systematically and rapidly once its sequence and the number of
      protons attached are specified, are the main advantages of the present method.

PMID- 16978874
TI  - Genetics of resistance to HIV infection: Role of co-receptors and co-receptor
      ligands.
AB  - Susceptibility to HIV infection and AIDS progression is variable among
      individuals and populations, and in part genetically determined. Genetic variants
      of genes encoding HIV co-receptors and their chemokine ligands have been
      described, and some of these variants were associated with resistance to HIV
      infection and/or disease progression. We review here the reported data regarding
      the variants of the CCR5, CCR2, CX3CR1, MIP-1alpha/CCL3, MIP-1beta/CCL4,
      RANTES/CCL5 and SDF-1/CXCL12 genes. The Delta32 deletion mutant of CCR5,
      resulting in a non-functional receptor not reaching the cell surface, is
      unambiguously associated with strong, although incomplete, resistance to HIV
      infection for homozygotes, and retarded progression for heterozygotes. Specific
      haplotypes encompassing the CCR5 and CCR2 loci, and the copy number of the CCL3L1
      gene, have also been convincingly correlated with delayed progression. For other
      gene variants, involving CXCL12/SDF-1 and CX3CR1, conclusive evidence for their
      relevance in the frame of HIV susceptibility is still lacking.

PMID- 16978875
TI  - A genome wide analysis of ubiquitin ligases in APP processing identifies a novel
      regulator of BACE1 mRNA levels.
AB  - Proteolysis of beta-amyloid precursor protein (APP) into amyloid beta peptide
      (Abeta) by beta- and gamma-secretases is a critical step in the pathogenesis of
      Alzheimer's Disease (AD), but the pathways regulating secretases are not fully
      characterized. Ubiquitinylation, which is dysregulated in AD, may affect APP
      processing. Here, we describe a screen for APP processing modulators using an
      siRNA library targeting 532 predicted ubiquitin ligases. Seven siRNA pools
      diminished Abeta production. Of these, siRNAs targeting PPIL2 (hCyp-60)
      suppressed beta-site cleavage. Knockdown of PPIL2 mRNA decreased BACE1 mRNA,
      while overexpression of PPIL2 cDNA enhanced BACE1 mRNA levels. Microarray
      analysis of PPIL2 or BACE1 knockdown indicated that genes affected by BACE1
      knockdown are a subset of those dependent upon PPIL2; suggesting that BACE1
      expression is downstream of PPIL2. The association of PPIL2 with BACE expression
      and its requirement for Abeta production suggests new approaches to discover
      disease modifying agents for AD.

PMID- 16978876
TI  - Involvement of DRG11 in the development of the primary afferent nociceptive
      system.
AB  - During development, dorsal root ganglia (DRG) neurons differentiate in various
      subpopulations, nociceptive neurons belonging in the small-diameter class. This
      study addresses the role played by DRG11, a transcription factor expressed in the
      spinal area of projection of small-diameter DRG neurons, in the development of
      the primary afferent system. The various subclasses of DRG neurons were compared
      between wild-type and Drg11(-/-) mice at embryonic and postnatal life. In Drg11(
      /-) mice, numbers of small peptidergic and non-peptidergic DRG neurons were
      decreased at P7 concomitant with abnormal cell death. Innervation by small DRG
      neurons was impaired in cutaneous, visceral and deep tissues. Large DRG neurons
      were not affected. The data point to a role for DRG11 in early postnatal survival
      of normally generated small primary afferent neurons innervating various kinds of
      peripheral tissues, which would explain the nociceptive deficits observed in
      Drg11-null mutant mice.

PMID- 16978877
TI  - Pre-neurodegeneration of mitral cells in the pcd mutant mouse is associated with
      DNA damage, transcriptional repression, and reorganization of nuclear speckles
      and Cajal bodies.
AB  - DNA damage and impairment of its repair underlie several neurodegenerative
      diseases. The Purkinje cell degeneration (pcd) mutation causes the loss of Nna1
      expression and is associated with a selective and progressive degeneration of
      specific neuronal populations, including mitral cells in the olfactory bulb.
      Using an in situ transcription assay, molecular markers for both nuclear
      compartments and components of the DNA damage/repair pathway, and ultrastructural
      analysis, here we demonstrate that the pcd mutation induces the formation of DNA
      damage/repair foci in mitral cells. Furthermore, this effect is associated with
      transcriptional inhibition, heterochromatinization, nucleolar segregation and the
      reorganization of nuclear speckles of splicing factors and Cajal bodies. The most
      significant cytoplasmic alteration observed was a partial replacement of rough
      endoplasmic reticulum cisternae by a larger amount of free ribosomes, while other
      organelles were structurally preserved. The tools employed in this work may be of
      use for the early detection of predegenerative processes in neurodegenerative
      disorders and for validating rescue strategies.

PMID- 16978878
TI  - Labeled lines in the retinotectal system: markers for retinorecipient sublaminae
      and the retinal ganglion cell subsets that innervate them.
AB  - Axons of retinal ganglion cells (RGCs) carry visual information to the brain. In
      most vertebrates, the major synaptic target of RGCs is the optic tectum. In the
      chick, RGC axons form synapses in just 4 of 16 histologically recognizable
      laminae (the retinorecipient laminae [RRLs]), and arbors of individual RGCs are
      confined to a single RRL. To analyze the development and function of these
      parallel pathways, markers are required that selectively label them. Here, we
      have identified molecular markers for individual RRLs and for RGCs that project
      to them. Some of the markers may mediate or modulate signaling through the
      separate pathways: neuropeptides (substance P, neuromedin B, somatostatin-I and 
      II) and their receptors (substance P receptor), neurotransmitter synthetic
      enzymes (choline acetyltransferase) and the corresponding receptors
      (acetylcholine receptor beta2) and calcium-binding proteins (parvalbumin and
      calbindin). Other markers are adhesive proteins that could mediate selective
      connectivity of RGC subsets within specific RRLs (cadherin-7, cadherin-11, reelin
      and neuropilin-1). We further show that RGC subsets whose axons project to
      specific RRLs are heterogeneous with respect to the retinal sublaminae within
      which their dendrites arborize. Our results define laminar-specified circuits
      from retina to brain and support a model in which RGCs transmit information from
      multiple sources to single central laminae, where it can be integrated.

PMID- 16978879
TI  - Human west nile virus neuroinvasive disease in Texas, 2003 epidemic: regional
      differences.
AB  - PURPOSE: Arboviral diseases, such as West Nile virus (WNV) epizootics, tend to be
      geographically unique because of the biomes that support the vector(s) and
      reservoir host(s). Understanding such details aids in preventive efforts. We
      studied the 2003 epidemic of human West Nile neuroinvasive disease (WNND) in
      Texas because it initially appeared that incidence was not uniform across regions
      of the state. METHODS: The epidemic was described by age, sex, and region of
      residence. These variables were used to compare age-specific incidence,
      standardized cumulative incidence, and age-adjusted relative risk (RR). We
      verified case data and used routine software, with population estimates from the
      US Census Bureau. RESULTS: Regardless of sex, risk increased with age. Males had
      the greater risk (RR, 1.69); however, males aged 5 to 17 years had the greatest
      RR. Of the five regions compared, two posed more (RRs, 7.98 and 2.14) and one
      posed less (RR, 0.40) risk than the remainder of the state. Proportions of Culex
      vector species differed significantly between regions. CONCLUSIONS: During 2003,
      the risk for WNND varied considerably across Texas. This suggests that various
      risks for WNV infection deserve additional research for preventive interventions
      to be regionally appropriate and effective.

PMID- 16978880
TI  - Transmission electron microscopy of the bacterial nucleoid.
AB  - Water-containing biological material cannot withstand the vacuum of the
      transmission electron microscope. The classical solution to this problem has been
      to dehydrate chemically fixed biological samples and then embed them in resin.
      During such treatment, the bacterial nucleoid is especially prone to aggregation,
      which affects its global shape and fine structure. Initial attempts to deal with
      aggregation by optimizing chemical fixation yielded contradictory results. Two
      decades ago, the situation improved with the introduction of freeze-substitution.
      This method is based on dehydration of unfixed cryo-immobilized samples at low
      temperature, which substantially reduces aggregation. As a result, the global
      shape of the nucleoid can be fairly well defined. Overall, in actively growing
      bacteria, the nucleoids are dispersed and "coralline" but become more confined
      when growth ceases. However, it is usually impossible to determine the molecular
      arrangement of DNA in the nucleoids of freeze-substituted bacteria because
      crystallization and the subsequent removal of water during substitution result in
      unavoidable distortions at the ultrastructural level. Recently, cryo-electron
      microscopy of vitreous sections has enabled the fully hydrated bacterial nucleoid
      to be studied close to the native state. Such studies have revealed aspects of
      bacterial nucleoid organization that are not preserved by freeze-substitution,
      including locally parallel or twisted bundles of DNA filaments, which are more
      frequently observed once bacterial growth has stopped, whereas in actively
      growing bacteria, the DNA is seen to be in a mostly disordered pattern.

PMID- 16978882
TI  - Controlled Support MEG imaging.
AB  - In this paper, we present a novel approach to imaging sparse and focal neural
      current sources from MEG (magnetoencephalography) data. Using the framework of
      Tikhonov regularization theory, we introduce a new stabilizer that uses the
      concept of controlled support to incorporate a priori assumptions about the area
      occupied by focal sources. The paper discusses the underlying Tikhonov theory and
      its relationship to a Bayesian formulation which in turn allows us to interpret
      and better understand other related algorithms.

PMID- 16978881
TI  - Weaker top-down modulation from the left inferior frontal gyrus in children.
AB  - Previous studies have shown that developmental changes in the structure and
      function of prefrontal regions can continue throughout childhood and adolescence.
      Our recent results suggested a role for the left inferior frontal cortex in
      modulating task-dependent shifts in effective connectivity when adults focus on
      orthographic versus phonological aspects of presented words. Specifically, the
      top-down influence of the inferior frontal cortex determined whether incoming
      word-form information from the fusiform gyrus would have a greater impact on the
      parietal areas involved in orthographic processing or temporal areas involved in
      phonological processing (Bitan, T., Booth, J.R., Choy, J., Burman, D.D.,
      Gitelman, D.R. and Mesulam, M.-M., 2005. Shifts of Effective Connectivity within
      a Language Network during Rhyming and Spelling. J. Neurosci. 25, 5397-5403.). In
      the current study, we find that children displayed an identical pattern of task
      dependent functional activations within this network. In comparison to adults,
      however, children had significantly weaker top-down modulatory influences
      emanating from the inferior frontal area. Adult language processing may thus
      involve greater top-down cognitive control compared to children, resulting in
      less interference from task-irrelevant information.

PMID- 16978883
TI  - Methylphenidate modulates cerebral post-stroke reorganization.
AB  - OBJECTIVE: We hypothesized that a single dose of methylphenidate (MP) would
      modulate cerebral motor activation and behavior in patients having suffered a
      subcortical stroke. METHODS: Eight men with a single stroke on the corticospinal
      tract resulting in a pure motor hemiparesia were included in a randomized, cross
      over, double-blind, placebo-controlled study. Patients were first evaluated 17
      days after stroke onset by validated neurological scales, motor tests and fMRI
      (flexion/extension of the digits) after 20 mg MP or placebo. Seven days later,
      the patients underwent the same protocol and received the drug they had not taken
      at the first evaluation. Each patient was his own control. RESULTS: Placebo
      intake did not change performance. MP compared to placebo elicited a significant
      improvement in motor performance of the affected hand at the finger tapping test.
      MP induced: (1) a hyperactivation of the ipsilesional primary sensorimotor cortex
      including the motor hand and face areas and of the contralesional premotor
      cortex; (2) a hypoactivation of the ipsilesional anterior cingulum.
      Hyperactivation in the face motor area correlated positively with the improvement
      in performance. CONCLUSION: We demonstrated that the reorganized network may
      efficiently be targeted by the drug and that the effect of MP might partly rely
      on an improvement in attention/effort through cingulum modulation.

PMID- 16978884
TI  - White matter growth as a mechanism of cognitive development in children.
AB  - We examined the functional role of white matter growth in cognitive development.
      Specifically, we used hierarchical regression analyses to test the unique
      contributions of age versus white matter integrity in accounting for the
      development of information processing speed. Diffusion tensor imaging was
      acquired for 17 children and adolescents (age range 6-17 years), with apparent
      diffusion coefficient (ADC) and fractional anisotropy (FA) calculated for 10
      anatomically defined fiber pathways and 12 regions of hemispheric white matter.
      Measures of speeded visual-spatial searching, rapid picture naming, reaction time
      in a sustained attention task, and intelligence were administered. Age-related
      increases were evident across tasks, as well as for white matter integrity in
      hemispheric white matter. ADC was related to few measures. FA within multiple
      hemispheric compartments predicted rapid picture naming and standard error of
      reaction time in sustained attention, though it did not contribute significantly
      to the models after controlling for age. Independent of intelligence, visual
      spatial searching was related to FA in a number of hemispheric regions. A novel
      finding was that only right frontal-parietal regions contributed uniquely beyond
      the effect of age in accounting for performance: age did not contribute to visual
      spatial searching when FA within these regions was first included in the models.
      Considering we found that both FA in right frontal-parietal regions and speed of
      visual-spatial searching increased with age, our findings are consistent with the
      growth of regional white matter organization as playing an important role in
      increased speed of visual searching with age.

PMID- 16978885
TI  - Evolution of Piperales--matK gene and trnK intron sequence data reveal lineage
      specific resolution contrast.
AB  - Piperales represent the largest basal angiosperm order with a nearly worldwide
      distribution. The order includes three species rich genera, Piper (ca. 2000
      species), Peperomia (ca. 1500-1700 species), and Aristolochia s. l. (ca. 500
      species). Sequences of the matK gene and the non-coding trnK group II intron are
      analysed for a dense set of 105 taxa representing all families (except
      Hydnoraceae) and all generic segregates (except Euglypha within Aristolochiaceae)
      of Piperales. A large number of highly informative indels are found in the
      Piperales trnK/matK dataset. Within a narrow region approximately 500 nt
      downstream in the matK coding region (CDS), a length variable simple sequence
      repeat (SSR) expansion segment occurs, in which insertions and deletions have led
      to short frame-shifts. These are corrected shortly afterwards, resulting in a
      maximum of six amino acids being affected. Furthermore, additional non-functional
      matK copies were found in Zippelia begoniifolia, which can easily be
      discriminated from the functional open reading frame (ORF). The trnK/matK
      sequence data fully resolve relationships within Peperomia, whereas they are not
      effective within Piper. The resolution contrast is correlated with the rate
      heterogeneity between those lineages. Parsimony, Bayesian and likelihood analyses
      result in virtually the same topology, and converge on the monophyly of
      Piperaceae and Saururaceae. Lactoris gains high support as sister to
      Aristolochiaceae subf. Aristolochioideae, but the different tree inference
      methods yield conflicting results with respect to the relationships of subfam.
      Asaroideae. In Piperaceae, a clade formed by the monotypic genus Zippelia and the
      small genus Manekia (=Sarcorhachis) is sister to the two large genera Piper and
      Peperomia.

PMID- 16978886
TI  - Accuracy and test-retest precision of quantitative cartilage morphology on a 1.0
      T peripheral magnetic resonance imaging system.
AB  - OBJECTIVE: Quantitative magnetic resonance imaging (qMRI) of knee cartilage
      morphology is a powerful research tool but relies on expensive and often
      inaccessible 1.5 T whole-body equipment. Here we examine the reproducibility and
      accuracy of qMRI at 1.0 T by direct comparison with previously validated
      technology. METHODS: Coronal images of the knee were obtained in six healthy and
      six osteoarthritic participants. Two data sets were acquired with a 1.5T whole
      body magnetic resonance imaging (MRI) system and two with a 1.0 T peripheral MRI
      system, with repositioning between scans. Proprietary software was used to
      analyze surface area, volume, and thickness of femoral and tibial cartilage.
      RESULTS: At 1.0 T, precision errors for surface areas (root-mean-square (RMS)
      coefficient of variation (CV%)=1.7-2.6%) were higher than those at 1.5 T (1.0
      2.1%). For volume and thickness, precision errors were 2.9-5.5% at 1.0 T compared
      to 1.6-3.4% at 1.5 T. High levels of agreement were found between the two
      scanners over all plates. With the exception of lateral femoral cartilage (volume
      and thickness), no statistically significant systematic bias was found between
      1.0 T and 1.5 T. CONCLUSIONS: This is the first reported study to show that knee
      cartilage morphology can be determined with a reasonable degree of accuracy and
      precision using a 1.0 T peripheral scanner. Peripheral MRI is less costly, can be
      performed in clinical offices, and is associated with higher patient comfort and
      tolerance than 1.5 T whole-body MRI. Implementation of qMRI with peripheral
      systems may thus permit its more widespread use in clinical research and patient
      care.

PMID- 16978887
TI  - Substantia nigra role in fear conditioning consolidation.
AB  - The substantia nigra (SN) is known to be involved in the memorization of several
      conditioned responses. To investigate the role of the SN in fear conditioning
      consolidation this neural site was subjected to fully reversible tetrodotoxin
      (TTX) inactivation during consolidation in adult male Wistar rats which had
      undergone fear training to acoustic CS and context. TTX was stereotaxically
      administered to different groups of rats at increasing intervals after the
      acquisition session. Memory was assessed as conditioned freezing duration
      measured during retention testing, always performed 72 and 96 h after TTX
      administration. In this way there was no interference with normal SN function
      during either acquisition or retrieval phases, so that any amnesic effect could
      be due only to consolidation disruption. The results show that SN functional
      integrity is necessary for contextual fear response consolidation up to the 24-h
      after-acquisition delay. On the contrary SN functional integrity was shown not to
      be necessary for the consolidation of acoustic CS fear responses. The present
      findings help to elucidate the role of the SN in memory consolidation and better
      define the neural circuits involved in fear memories.

PMID- 16978889
TI  - Succinic acid production from Bacteroides fragilis: process optimization and
      scale up in a bioreactor.
AB  - We report the effect of different physiological and nutritional parameters on
      succinic acid production from Bacteroides fragilis. This strain initially
      produced 0.70gL(-1) of succinic acid in 60h. However, when process optimization
      was employed, 5.4gL(-1) of succinic acid was produced in medium consisting of
      glucose (1.5%); tryptone (2.5%); Na(2)CO(3) (1.5%), at pH 7.0, when inoculated
      with 4% inoculum and incubated at 37 degrees C, 100rpm for 48h. A marked
      enhancement in succinic acid production was observed when the optimized
      conditions were employed in a 10L bioreactor. A total of 12.5gL(-1) of succinic
      acid was produced in 30h. This is approximately 12-fold increase in succinic acid
      production when compared to the initial un-optimized medium production. This
      enhancement in succinic acid production may be due to the control of CO(2) supply
      and the impeller speed. This is also resulted in the reduction of the production
      time. The present study provides useful information to the industrialists seeking
      environmentally benign technology for the production of bulk biomolecules through
      manipulation of various chemical parameters.

PMID- 16978888
TI  - Blunted hippocampal, but not striatal, acetylcholine efflux parallels learning
      impairment in diencephalic-lesioned rats.
AB  - A rodent model of diencephalic amnesia, pyrithiamine-induced thiamine deficiency
      (PTD), was used to investigate the dynamic role of hippocampal and striatal
      acetylcholine (ACh) efflux across acquisition of a nonmatching-to-position (NMTP)
      T-maze task. Changes in ACh efflux were measured in rats at different time points
      in the acquisition curve of the task (early=day 1, middle=day 5, and late=day
      10). Overall, the control group had higher accuracy scores than the PTD group in
      the latter sessions of NMTP training. During the three microdialysis sampling
      points, all animals displayed significant increases in ACh efflux in both
      hippocampus and striatum, while performing the task. However, on day 10, the PTD
      group showed a significant behavioral impairment that paralleled their blunted
      hippocampal--but not striatal--ACh efflux during maze training. The results
      support selective diencephalic-hippocampal dysfunction in the PTD model. This
      diencephalic-hippocampal interaction appears to be critical for successful
      episodic and spatial learning/memory.

PMID- 16978890
TI  - The proteomic study of sodium butyrate antiproliferative/cytodifferentiation
      effects on K562 cells.
AB  - Employing methods of cell biology and proteome analysis tools, we examined
      effects of an inhibitor of histone deacetylases, sodium butyrate (SB), on the
      proliferation/differentiation characteristics of chronic myelogenous leukemia
      (CML)-derived cells K562. SB suppressed proliferation of K562 cells by inducing
      cell cycle arrest in G1 phase, which was followed by their transition to G0 phase
      (decrease of Ki-67 antigen-positive cells) and erythroid differentiation
      (increased glycophorin A expression and synthesis of hemoglobins). Neither
      terminal apoptosis (low counts of TUNEL-positive cells) nor necrosis (moderate
      counts of propidium iodide-positive cells) occurred. Importantly, SB attenuated
      protein expression of CML-related chimeric kinase BCR-ABL that is responsible for
      the deregulated proliferation of CML cells. The proteomic analysis (2-D
      electrophoresis combined with MALDI-TOF mass spectrometry and/or Western
      blotting) revealed several proteins that were differentially expressed or their
      mobility was altered due to butyrate treatment, namely, HSP90, HSP70, p23,
      cyclophilin A (CYPA), prefoldin2 (PFD2) and alpha-, gamma-, epsilon-human globin
      chains. Perturbation of HSP90 multichaperone complex of which BCR-ABL is the
      client protein is presumably a cause of BCR-ABL suppression. Changes in other
      proteins with chaperonic functions, CYPA and PFD2, may reflect SB
      antiproliferative and cytodifferentiation effects.

PMID- 16978891
TI  - Wound healing activity of NOE-aspirin: a pre-clinical study.
AB  - Aspirin, one of the oldest non-steroidal anti-inflammatory drugs, impedes tissue
      repair by virtue of retarding inflammation. The present study was undertaken to
      find out if linking of nitrooxyethyl ester to aspirin reverses its healing
      depressant propensity. Nitrooxyethyl ester of aspirin (NOE-Asp) was synthesized
      in our laboratory through well-established synthetic pathway, starting from
      aspirin through esterification with ethylene glycol and nitration with a mixture
      of nitric and sulfuric acids at 0 degrees C. The effect of NOE-Asp on phases of
      healing such as collagenation, wound contraction and epithelialization and on
      scar size of healed wound was evaluated in three wound models-incision, dead
      space, and excision wounds. To assess its influence on the oxidative stress, the
      levels of glutathione (GSH) and thiobarbiturate reactive species (TBARS) were
      also determined in 10-day-old granulation tissue. NOE-Asp was further screened
      for its anti-inflammatory activity in rat paw edema model. NOE-Asp promoted
      collagenation (increase in breaking strength, granulation weight, and collagen
      content), wound contraction, and epithelialization phases of healing. NOE-Asp
      also showed a significant antioxidant effect in 10-day-old granulation tissue as
      compared to aspirin. The results vindicate our assumption that the esterification
      of aspirin with nirooxyethyl group reverses the healing-suppressant effect of
      aspirin. The compound also showed equipotent anti-inflammatory activity as
      aspirin.

PMID- 16978892
TI  - COL-3 inhibition of collagen fragmentation in ruptured cranial cruciate ligament
      explants from dogs with stifle arthritis.
AB  - Inhibition of collagen fragment generation in canine cranial cruciate ligament
      (CCL) explant cultures by the matrix metalloprotease inhibitor (6-demethyl)-6
      deoxy-4-dedimethylamino tetracycline (COL-3) was studied. Cranial cruciate
      ligament specimens were collected from dogs with inflammatory stifle
      arthritis/CCL rupture and dogs with normal stifles. Explant cultures from each
      CCL specimen included one COL-3 treated explant and a baseline control; explants
      from 12 ruptured CCLs were prepared in triplicate and a protease inhibitor
      cocktail positive control was used. Explant supernatants were analyzed for
      generation of collagen fragments after two days. Treatment of ruptured CCL
      explants with 10(-4)M COL-3 decreased generation of collagen fragments. The
      extent of this inhibition was increased in explants treated with a protease
      inhibitor cocktail. Generation of collagen fragments was increased in ruptured
      CCLs, when compared with intact CCLs. It is concluded that generation of collagen
      fragments was increased in pathological ruptured CCL explants. This degradation
      could be significantly inhibited in vitro by 10(-4)M COL-3.

PMID- 16978893
TI  - Microassays for a set of enzymes in individual small marine copepods.
AB  - Fluorogenic assays for a set of five hydrolytic enzymes involved in digestion and
      food utilization (alanine and arginine aminopeptidase, lipase/esterase,
      chitobiase, and beta-glucosidase) were optimized to measure activities of these
      enzymes in the same extracts of individual small North Sea copepods. The enzyme
      activities of Acartia clausi, Centropages typicus, Corycaeus anglicus,
      Paracalanus parvus, and Temora longicornis showed distinct species specific
      activity patterns, but also high intra-specific variability. Protein, lipids,
      carbon and nitrogen (C, N) were determined with micro-scale assays in individual
      copepods or in batches of 10 to 50 animals. Water soluble protein contents ranged
      from 16% to 38%, and lipid contents from 2.4% to 5.5% of dry mass. The molar C/N
      ratios were between 4.1 and 4.5. The presented microassays provide suitable tools
      for studying physiological reactions of copepods and other small pelagic
      crustaceans in response to variable environmental conditions.

PMID- 16978894
TI  - Drinking in juvenile Atlantic salmon (Salmo salar L.) in response to feeding and
      activation of the endogenous renin-angiotensin system.
AB  - Drinking rate and rectal fluid production of juvenile Atlantic salmon (1-2 g) in
      freshwater were investigated in unfed fish and recently fed fish. Drinking was
      also investigated following activation of the renin-angiotensin system (RAS) by
      two hypotensive agents, a nitric oxide (NO) donor sodium nitroprusside (SNP) and
      bacterial lipopolysaccharide (LPS). In unfed fish the basal drinking rate was
      0.13 microL g(-1) h(-1) and rectal fluid production was 0.076 microL g(-1) h(-1).
      In recently fed fish both drinking rate and rectal fluid production increased
      significantly by about fivefold compared to unfed fish, and similar values were
      obtained for fish exposed to PS for 24 h. Exposure to SNP resulted in about a
      tenfold elevation of drinking rate and rectal fluid production, compared to unfed
      fish. Absorption of water by the gut was in the range 35-60% for all treatments.
      Drinking may have a role in processing food in the gut and the fluid in the gut
      may subjected to absorptive and secretory processes. The most likely route for
      removal of water absorbed by the gut is excretion via the kidney and this would
      result in an increased osmoregulatory burden on the fish. In polluted waters
      drinking could be increased through stimulation of the endogenous RAS by
      vasodilators, e.g., LPS and the gut could be a significant target for toxin
      exposure.

PMID- 16978895
TI  - Characterization of cDNAs encoding cholesterol side chain cleavage and 3beta
      hydroxysteroid dehydrogenase in the freshwater stingray Potamotrygon motoro.
AB  - The interrenal gland (adrenocortical homolog) of elasmobranchs produces a unique
      steroid, 1alpha-hydroxycorticosterone (1alpha-B). The synthesis of this and most
      other steroids requires both cholesterol side chain cleavage (CYP11A) and 3beta
      hydroxysteroid dehydrogenase (HSD3). To facilitate the study of elasmobranch
      steroidogenesis, we isolated complementary DNAs encoding CYP11A and HSD3 from the
      freshwater stingray Potamotrygon motoro. The P. motoro CYP11A (2182 bp total
      length) and HSD3 (2248 bp total length) cDNAs harbor open reading frames that
      encode proteins of 542 and 376 amino acids (respectively) that are similar
      (CYP11A: 39-61% identical; HSD3: 36-53% identical) to their homologs from other
      vertebrates. In molecular phylogenetic analysis, P. motoro CYP11A segregates with
      CYP11A proteins (and not with related CYP11B proteins) and P. motoro HSD3
      segregates with steroidogenic HSD3 proteins from other fishes. CYP11A and HSD3
      mRNA is found only in interrenal and gonadal tissues, indicating de novo
      steroidogenesis is restricted to these tissues. Because 1alpha-B is thought to
      act in the elasmobranch response to hydromineral disturbances, we examined the
      effect of adapting P. motoro to 10 ppt seawater on mRNAs encoding steroidogenic
      genes. The P. motoro response to this salinity challenge does not include
      interrenal hypertrophy or an increase in the levels of interrenal CYP11A, HSD3 or
      steroidogenic acute regulatory protein (StAR) mRNA. This study is the first to
      isolate full length cDNAs encoding elasmobranch CYP11A and HSD3 and the first to
      examine the regulation of steroidogenic genes in elasmobranch interrenal cells.

PMID- 16978896
TI  - Moderate coffee and alcohol consumption improves the estrogen metabolite profile
      in adjuvant treated breast cancer patients: a pilot study comparing pre- and post
      operative levels.
AB  - Most, but not all, studies have found that women with a high urinary 2
      hydroxyestrogen (2OHE) to 16alpha-hydroxyestrone (16alphaOHE1) ratio are at
      reduced risk for breast cancer and have a better prognosis. The aim was to
      identify factors associated with the pre-operative 2OHE to 16alphaOHE1 ratio and
      factors that predicted the change in the ratio between the pre-operative visit
      and first follow-up visit three to six months post-operatively among 59 women
      with primary ER positive breast cancer tumors. Body measurements, questionnaires
      and blood samples for measurements of the 2OHE and 16alphaOHE1 plasma levels and
      CYP1A2 *1F genotyping were collected at both visits. Post-operatively, 15 women
      received tamoxifen, 30 women tamoxifen and radiotherapy concomitantly, and 14
      women radiotherapy. The pre-operative ratio was not correlated with tumor
      characteristics, but was significantly higher in women who consumed three or more
      cups of coffee daily (p = 0.009). The number of CYP1A2 *1F C-alleles was
      correlated with a lower ratio at both visits (p = 0.13 and p = 0.02,
      respectively). The ratio increased between the two visits in 69.5% of the women.
      The factors associated with a significant increase in the ratio were concomitant
      tamoxifen and radiotherapy (p = 0.006), increasing alcohol consumption (p =
      0.006), and a high coffee consumption (p = 0.03), but not age or CYP1A2 *1F
      genotype. In this pilot study, breast cancer patients who started tamoxifen
      during radiotherapy and who had a moderate coffee and alcohol consumption
      demonstrated a significant improvement in their estrogen metabolite profile
      between the pre- and post-operative visits.

PMID- 16978897
TI  - Zoonotic infections among veterinarians in Turkey: Crimean-Congo hemorrhagic
      fever and beyond.
AB  - OBJECTIVES: We aimed to determine the seroprevalence of Crimean-Congo hemorrhagic
      fever (CCHF) virus, Brucella spp, and Coxiella burnetii among veterinarians in a
      highly endemic and a non-endemic region for these infections in Turkey. METHODS:
      The antibody levels against these three infections were surveyed. Eighty-three
      veterinarians were included from two distinct geographic regions. RESULTS: CCHF
      IgG positivity (3% vs. 0%) and Brucella agglutination titer of > or =1/160 (33%
      vs. 5%) were more common in the endemic region, whereas the rates of Coxiella
      burnetii antibodies were similar (7% and 8%). A history of tick bite was
      significantly more common in the endemic region (35% vs. 12%, p=0.011). A
      multivariate analysis was performed among the veterinarians living in the endemic
      area, and percutaneous injuries were found to be associated with Brucella
      infection (OR 1.8, CI 1.09-3, p=0.022). CONCLUSIONS: Veterinarians should protect
      themselves against tick bites, and should use masks to prevent transmission by
      inhalation of zoonotic infections in endemic countries.

PMID- 16978898
TI  - Multidrug-resistant and extended-spectrum beta-lactamase (ESBL)-producing
      Salmonella enterica (serotypes Typhi and Paratyphi A) from blood isolates in
      Nepal: surveillance of resistance and a search for newer alternatives.
AB  - OBJECTIVES: We evaluated the prevalence of multidrug resistance (MDR) and
      production of extended spectrum beta-lactamase (ESBL) by Salmonella enterica
      (serotypes Typhi and Paratyphi A) in a teaching hospital in Nepal. The MDR
      strains of S. enterica were also tested for susceptibility to newer antibiotics.
      METHODS: Blood cultures were obtained from 4105 patients with febrile illnesses.
      Isolates of S. enterica were serotyped and antibiotic susceptibility testing was
      carried out using disk diffusion (Kirby-Bauer) and E-tests. ESBL screening and
      phenotype confirmation were done following National Committee for Clinical
      Laboratory Standards (NCCLS) recommendations for Escherichia coli. RESULTS: A
      total of 541 isolates of S. enterica serotypes Typhi (47%) and Paratyphi A (53%)
      were grown. Twenty-eight isolates (5%) of S. enterica were resistant to two or
      more antibiotics (MDR isolates), with a greater prevalence among serotype
      Paratyphi A (7%). All ESBL producers (three isolates) were serotype Paratyphi A.
      Most of the MDR S. enterica showed reduced susceptibility to ampicillin,
      chloramphenicol, trimethoprim-sulfamethoxazole, ofloxacin, and ciprofloxacin, and
      had good susceptibility to extended-spectrum cephalosporins and carbapenems.
      Among the fluoroquinolones, gatifloxacin demonstrated better in vitro activity
      compared to levofloxacin, ciprofloxacin, and ofloxacin. CONCLUSIONS: A greater
      prevalence of S. enterica serotype Paratyphi A with higher rates of multidrug
      resistance and ESBL production is concerning for natives as well as travelers in
      Nepal since the current typhoid vaccines do not provide protection against this
      serotype.

PMID- 16978899
TI  - [The stereotactic body radiation therapy: initiation and clinical program].
AB  - We fully describe an innovative radiotherapy technique called Stereotactic Body
      Radiation Therapy (SBRT), and explain how this technique is commonly used for
      clinical purpose at the anticancer center Leon-Berard (Lyon, France). In this
      technique, a non-invasive stereotactic body frame is used to locate the tumor
      site with a great precision. This frame is combined with a system, which enables
      to track the respiratory motions (Active Breathing Control (ABC) or diaphragmatic
      compression (DC)) in order to reduce the treatment margins for organ motion due
      to breathing. Thus, the volume of normal tissues that will be irradiated is
      considerably reduced. The dosimetry is realized with 3 CT exams performed in
      treatment conditions. The 3D patient "repositioning" is done with a volume CT
      acquisition (kV) combined with orthogonal images (kV and MV). The SBRT requires a
      system to limit the organ motions. Although the ABC seems to be more fastidious
      for patient, it would enable to use smaller margins than with DC technique.
      Nevertheless, the ABC is not compatible with volume CT acquisitions, which
      considerably improve the patient repositioning. In conclusion, the quality of
      repositioning and the high level of conformation enable to deliver high
      equivalent doses (>100 Gy) in hypofractionated mode, without increasing the
      treatment toxicity. The SBRT employs the last technologic innovations in
      radiotherapy and is therefore considered as a new efficient tool for solid tumors
      treatment.

PMID- 16978900
TI  - Cellular and molecular hemocyte responses of the Pacific oyster, Crassostrea
      gigas, following bacterial infection with Vibrio aestuarianus strain 01/32.
AB  - The strategies used by bacterial pathogens to circumvent host defense mechanisms
      remain largely undefined in bivalve molluscs. In this study, we investigated
      experimentally the interactions between the Pacific oyster (Crassostrea gigas)
      immune system and Vibrio aestuarianus strain 01/32, a pathogenic bacterium
      originally isolated from moribund oysters. First, an antibiotic-resistant V.
      aestuarianus strain was used to demonstrate that only a limited number of
      bacterial cells was detected in the host circulatory system, suggesting that the
      bacteria may localize in some organs. Second, we examined the host defense
      responses to V. aestuarianus at the cellular and molecular levels, using flow
      cytometry and real-time PCR techniques. We showed that hemocyte phagocytosis and
      adhesive capabilities were affected during the course of infection. Our results
      also uncovered a previously-undescribed mechanism used by a Vibrio in the initial
      stages of host interaction: deregulation of the hemocyte oxidative metabolism by
      enhancing the production of reactive oxygen species and down-regulating
      superoxide dismutase (Cg-EcSOD) gene expression. This deregulation may provide an
      opportunity to the pathogen by impairing hemocyte functions and survival. These
      findings provide new insights into the cellular and molecular bases of the host
      pathogen interactions in C. gigas oyster.

PMID- 16978901
TI  - [How WHI study influences women doctors' behavior toward menopause. Gynecol
      Obstet Fertil 2006;34:499-505].

PMID- 16978902
TI  - Population genetic data on D1S80, D17S5, ApoB, COL2A1 and Ig-JH in Northeastern
      Thais.
AB  - Allele frequency distributions at five VNTR loci namely; D1S80, D17S5, ApoB,
      COL2A1 and Ig-JH were examined in Northeastern Thais. The number of alleles at
      each locus were 19, 13, 14, 6 and 8 with the heterozygous frequencies of 0.814,
      0.818, 0.676, 0.579 and 0.288, respectively. No significant deviations were found
      by statistical tests for Hardy-Weinberg equilibrium. The combined power of
      discrimination for all five loci was 0.99998.

PMID- 16978903
TI  - Estimation of postmortem interval from human pericardial fluid electrolytes
      concentrations in Chandigarh zone of India: log transformed linear regression
      model.
AB  - Estimation of postmortem interval from changes in postmortem pericardial fluid
      electrolytes concentration is the topic of discussion in the study. Querido
      [Querido D. Double logarithmic, linear relationship between plasma
      sodium/potassium concentration ratio and postmortem interval during the 6-96h
      postmortem period in rats. Forensic Sci Int 1990;44:125-34; Querido D.
      Linearization of the relationship between postmortem plasma chloride
      concentration and postmortem interval in rats. Forensic Sci Int 1990;45:117-27]
      and Singh et al. [Singh D, Prashad R, Parkash C, Bansal YS, Sharma SK, Pandey AN.
      Linearization of relationship between serum sodium, potassium concentration,
      their ratio and time since deaths in Chandigarh zone of north west India.
      Forensic Sci Int 2002;130:107; Singh D, Prashad R, Parkash C, Sharma SK, Pandey
      AN. Double logarithmic linear relationship between plasma chloride concentration
      and time since death in humans in Chandigarh zone of north west India. Legal Med
      2003;5:49-54] had demonstrated a highly significant double logarithmic linear
      relationship between the time since death and the plasma sodium/potassium ratio
      as well as with plasma chloride concentration in Wistar rats and human,
      respectively. In view of these facts, the present study was carried out to
      substantiate this propensity in this transcellular extension of blood plasma.
      Electrolytes analysis in postmortem pericardial fluid obtained from 311 subjects
      revealed that correlation of time since deaths with potassium, sodium/potassium
      ratio and phosphorus was highly significant (p<0.001) during 2.5-58h of deaths.
      Not withstanding, time since death although modulated by ambient temperature
      could be predicted by log transformed multiple regression equation derived from
      the combination of potassium, chloride and phosphorus electrolytes concentration
      with standard error (SE) of prediction (in log hours) of 0.1840h and by double
      logarithmic model with SE (in log hours) of 0.1959, 0.2068 and 0.2088h from
      potassium, sodium/potassium ratio and phosphorus electrolytes, respectively.

PMID- 16978904
TI  - Genetic polymorphisms of 17 Y-STRs haplotypes in Tibetan ethnic minority group of
      China.
AB  - Haplotypes and allele frequencies for the 17 Y-chromosomal STRs loci, namely
      DYS456, DYS389I, DYS390, DYS389II, DYS458, DYS19, DYS385a,b, DYS393, DYS391,
      DYS439, DYS635, DYS392, Y GATA H4, DYS437, DYS438, DYS448 were determined in a
      population sample of 112 healthy unrelated autochthonous Tibetan ethnic male
      individuals from Tibet of China. No shared haplotypes were observed. The gene
      diversity values for the Y-STRs loci ranged from 0.2052(DYS391) to
      0.9301(DYS385a,b). The results demonstrate that these loci will be very useful
      for human identification in forensic cases and paternity tests in Tibetan
      population of China.

PMID- 16978905
TI  - Free radicals and antioxidants in normal physiological functions and human
      disease.
AB  - Reactive oxygen species (ROS) and reactive nitrogen species (RNS, e.g. nitric
      oxide, NO(*)) are well recognised for playing a dual role as both deleterious and
      beneficial species. ROS and RNS are normally generated by tightly regulated
      enzymes, such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively.
      Overproduction of ROS (arising either from mitochondrial electron-transport chain
      or excessive stimulation of NAD(P)H) results in oxidative stress, a deleterious
      process that can be an important mediator of damage to cell structures, including
      lipids and membranes, proteins, and DNA. In contrast, beneficial effects of
      ROS/RNS (e.g. superoxide radical and nitric oxide) occur at low/moderate
      concentrations and involve physiological roles in cellular responses to noxia, as
      for example in defence against infectious agents, in the function of a number of
      cellular signalling pathways, and the induction of a mitogenic response.
      Ironically, various ROS-mediated actions in fact protect cells against ROS
      induced oxidative stress and re-establish or maintain "redox balance" termed also
      "redox homeostasis". The "two-faced" character of ROS is clearly substantiated.
      For example, a growing body of evidence shows that ROS within cells act as
      secondary messengers in intracellular signalling cascades which induce and
      maintain the oncogenic phenotype of cancer cells, however, ROS can also induce
      cellular senescence and apoptosis and can therefore function as anti-tumourigenic
      species. This review will describe the: (i) chemistry and biochemistry of ROS/RNS
      and sources of free radical generation; (ii) damage to DNA, to proteins, and to
      lipids by free radicals; (iii) role of antioxidants (e.g. glutathione) in the
      maintenance of cellular "redox homeostasis"; (iv) overview of ROS-induced
      signaling pathways; (v) role of ROS in redox regulation of normal physiological
      functions, as well as (vi) role of ROS in pathophysiological implications of
      altered redox regulation (human diseases and ageing). Attention is focussed on
      the ROS/RNS-linked pathogenesis of cancer, cardiovascular disease,
      atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus,
      neurodegenerative diseases (Alzheimer's disease and Parkinson's disease),
      rheumatoid arthritis, and ageing. Topics of current debate are also reviewed such
      as the question whether excessive formation of free radicals is a primary cause
      or a downstream consequence of tissue injury.

PMID- 16978906
TI  - Role of activator protein-1 on the effect of arginine-glycine-aspartic acid
      containing peptides on transforming growth factor-beta1 promoter activity.
AB  - While arginine-glycine-aspartic acid-based peptidomimetics have been employed for
      the treatment of cardiovascular disorders and cancer, their use in other contexts
      remains to be explored. Arginine-glycine-aspartic acid-serine induces
      Transforming growth factor-beta1 transcription in human mesangial cells, but the
      molecular mechanisms involved have not been studied extensively. We explored
      whether this effect could be due to Activator protein-1 activation and studied
      the potential pathways involved. Addition of arginine-glycine-aspartic acid
      serine promoted Activator protein-1 binding to its cognate sequence within the
      Transforming growth factor-beta1 promoter as well as c-jun and c-fos protein
      abundance. Moreover, this effect was suppressed by curcumin, a c-Jun N terminal
      kinase inhibitor, and was absent when the Activator protein-1 cis-regulatory
      element was deleted. Activator protein-1 binding was dependent on the activity of
      integrin linked kinase, as transfection with a dominant negative mutant
      suppressed both Activator protein-1 binding and c-jun and c-fos protein
      increment. Integrin linked kinase was, in turn, dependent on Phosphoinositol-3
      kinase activity. Arginine-glycine-aspartic acid-serine stimulated Phosphoinositol
      3 kinase activity, and Transforming growth factor-beta1 promoter activation was
      abrogated by the use of Phosphoinositol-3 kinase specific inhibitors. In summary,
      we propose that arginine-glycine-aspartic acid-serine activates Integrin linked
      kinase via the Phosphoinositol-3 kinase pathway and this leads to activation of c
      jun and c-fos and increased Activator protein-1 binding and Transforming growth
      factor-beta1 promoter activity. These data may contribute to understand the
      molecular mechanisms involved in the cellular actions of arginine-glycine
      aspartic acid-related peptides and enhance their relevance as these products
      evolve into clinical therapeutic use.

PMID- 16978907
TI  - Identification of human hepatic stimulator substance gene promoter and
      demonstration of dual regulation of AP1/AP4 cis-acting element in different cell
      lines.
AB  - Human hepatic stimulator substance (hHSS) is a newly identified growth-promoting
      factor in the liver. HSS is capable of stimulating hepatic regeneration in
      partial hepatectomized rats, thus, promoting growth of hepatic tumor cells. To
      understand and elucidate the transcriptional regulation of hHSS gene, the 4890bp
      of 5'-flanking region of the gene have been isolated and sequenced. The
      transcriptional start site, located at 248nt upstream from the ATG starting
      codon, was identified by 5'-rapid amplification cDNA end (5'-RACE). The classical
      promoter sequences, such as TATA box or GAATT were not identified in the promoter
      region, instead a GC-rich segment was formed (>70%) by expanding to a longer than
      400bp, and immediately upstream from the ATG start codon. The transient
      transfection assays, using promoter deletion constructs, showed that hHSS
      promoter was efficiently capable in driving the reporter expression not only in
      HepG2 cells, but also in Cos7 cells. A region spanning nucleotides in the range
      of -447 to -358bp revealed a negative regulation on promoter activity in HepG2
      cells, but with positive regulation in Cos7 and Hela cells. The promoter activity
      was obviously influenced by AP1/AP4 (-375/-369nt) mutation in these three cell
      lines. EMSAs showed that the site was recognized by AP1 in HepG2 cell, and only
      by an AP4 protein in Cos7 cells. The c-Jun bound to the promoter was further
      verified by supershift in HepG2 cells and human liver tissue. Chromatin immuno
      precipitation (ChIP) demonstrated that there was a direct association of c-Jun
      with hHSS promoter in HepG2 cells. The c-Jun strongly suppressed hHSS promoter
      activity in transient expression analyses in HepG2 cells. Mutations in the AP1
      binding sites rescued suppression caused by c-Jun, suggesting this was a direct
      regulation of the hHSS promoter. In contrast, there was no significant effect in
      c-Jun over-expressed Cos7 and Hela cells. The tissue-specific function of c-Jun
      in hHSS promoter activity may in part help explain the differences in biology
      function of hHSS between liver and non-liver cells.

PMID- 16978909
TI  - G protein beta2 subunit interacts directly with neuropathy target esterase and
      regulates its activity.
AB  - Neuropathy target esterase (NTE) was identified as the primary target of
      organophosphate compounds that cause a delayed neuropathy with degeneration of
      nerve axons. NTE is a novel phospholipase B anchored to the cytoplasmic face of
      endoplasmic reticulum and essential for embryonic and nervous development.
      However, little is known about the regulation of NTE. A human fetal brain cDNA
      library was screened for proteins that interact with NTE, Gbeta2 and Gbeta2-like
      I subunits were found to be able to bind the C-terminal of NTE in yeast. The
      interaction of Gbeta2 and NTE was confirmed by in vivo co-immunoprecipitation
      analysis in COS7 cells. Furthermore, depletion of Gbeta2 by RNA interference down
      regulated the activity of NTE but not its expression level. In addition, the
      activity of NTE was down regulated by the G protein signal pathway influencing
      factor, pertussis toxin, treatment in vivo. These findings suggest that Gbeta2
      may play a significant role in maintaining the activity of NTE.

PMID- 16978910
TI  - Ocular motor triad with single vision contact lenses compared to spectacle
      lenses.
AB  - AIM: Theoretically myopes are required to exert more accommodation and vergence
      when wearing single vision contact lenses compared to glasses and hypermetropes
      less. This study aims to quantify the effects clinically. METHOD: Thirty subjects
      (21 female, nine male, average age 21.0+/-2.2 years) with a range of refractive
      errors (-7.87 D to +3.50 D) viewed in a random order, static targets at 0.1, 0.5,
      1.0, 2.0, 3.0, 4.0 and 5.0 D accommodative demand that were matched for angular
      subtense. The subjects were fully corrected with spectacles and daily disposable
      contact lenses to their full prescription. Accommodation was monitored
      objectively with the PowerRefractor and Shin-Nippon SRW5000 and vergence and
      pupil size with the PowerRefractor. RESULTS: Myopes exerted greater accommodative
      effort for viewing near targets with contact lenses than glasses and
      hypermetropes less (r(2)=0.35, p=0.001 PowerRefractor). Myopes also exerted
      greater vergence effort for viewing near targets with contact lenses than glasses
      and hypermetropes less (r(2)=0.22, p<0.01). CONCLUSION: Theoretical calculation
      of the accommodative and vergence requirements with glasses compared to contact
      lenses reflect clinical findings, although there is reasonable variability
      between individuals.

PMID- 16978908
TI  - Functional assays for BRCA1 and BRCA2.
AB  - Genetic testing for the two major breast cancer susceptibility genes has now been
      available for several years with more than 70,000 people tested in the USA alone.
      While the current genetic testing identifies many sequence alterations there are
      problems with both sensitivity and specificity of the assay. In particular, the
      genetic testing is limited in its ability to determine which of the many missense
      mutations identified in BRCA1 and BRCA2 actually predispose to cancer and which
      are simply neutral alterations. Here we will focus on the limitations in test
      result interpretation and we will explore how biochemistry and cell biology can
      help to clarify these issues. Although we limit our discussion to genetic testing
      of BRCA1 and BRCA2, the problem is common to an expanding group of genes,
      including ATM and MSH2, in which germ-line missense mutations may also confer
      increased risk of cancer. Here we advocate the use of functional assays to
      complement genetic data in the analysis of unclassified missense mutations and
      propose a set of standards to conduct and interpret these assays.

PMID- 16978911
TI  - Current surgical treatment of squamous cell carcinoma of the head and neck.
AB  - Historically treatment of head and neck cancers involved surgical resection
      followed by radiation therapy for advanced tumors. Concurrent chemoradiation
      therapies have shown equal survival to surgical resection with better
      preservation of function. However, concurrent therapy does entail significant
      morbidity, and recent advances have been used to minimize that morbidity. Newer
      tumor specific medical therapies are anticipated to be less toxic while
      maintaining a high degree of efficacy. For resectable cancer, transoral laser
      microsurgery is a new trend in surgery for complete resection of tumors with
      preservation of function. Advanced reconstructive techniques that allow free
      transfer of soft tissue and bone from all over the body improve the functional
      and aesthetic outcomes following major ablative surgery. With successful surgical
      reconstruction, dental and prosthetic rehabilitation choices are enhanced.
      Advances in rehabilitation of speech following removal of the larynx have
      improved the quality of life post-laryngectomy patients. With these newer
      therapies and methods of reconstruction, each patient needs to be carefully
      evaluated to maximize the possibility of cure and level of function, and minimize
      the morbidity associated with treatment. Combined chemotherapy and radiation
      protocols are associated with increased acute and chronic toxicities that may
      affect the quality of life due to the impact upon oral disease and oral function.
      Oral care providers must be aware of advances in cancer management and
      implications for patient care to effectively care for these patients.

PMID- 16978912
TI  - Molecular analysis of anoikis resistance in oral cavity squamous cell carcinoma.
AB  - Oral cavity squamous cell carcinoma (OSCC) is one of the leading causes of cancer
      deaths worldwide and most of these deaths result from local-regional recurrence
      and metastases. Evasion of apoptosis is an important hallmark of cancer
      development and progression, and previous studies have shown that evasion of
      anoikis, or detachment-induced apoptosis, correlates with a more aggressive
      phenotype of carcinoma cells in OSCC. To elucidate the cytogenetic and molecular
      characteristics of anoikis resistance, we generated several cell lines and clones
      that displayed this cellular phenotype. To test the hypothesis that chromosomal
      alterations may underlie this phenotypic transformation, we used karyotype
      analysis to observe changes in the chromosomal structure of anoikis-sensitive and
      anoikis-resistant cell lines. We further hypothesized that a unique pattern of
      gene expression was induced by cell-detachment of anoikis-resistant cell lines,
      and cDNA microarray analysis was performed using a panel of anoikis-resistant
      oral cancer cell lines grown under attached and detached growth conditions. We
      identified S100P, KLK6 and CTNNAL1 as genes whose expression levels were
      differentially regulated in the anoikis-resistant cell lines compared to the
      anoikis-sensitive cells under detached conditions. These results were verified
      using real-time RT-PCR. The anoikis-resistant phenotype of squamous cell
      carcinoma has a distinct genetic expression pattern that is marked by chromosomal
      alterations that may contribute to differential expression of genes involved in
      diverse cellular functions. Therapies targeting these potential mediators of
      anoikis resistance may prove to be beneficial in the treatment of metastatic
      squamous cell carcinoma.

PMID- 16978913
TI  - Determinants of anti-benzo[a]pyrene diol epoxide-DNA adduct formation in
      lymphomonocytes of the general population.
AB  - We evaluated determinants of anti-benzo[a]pyrenediolepoxide-(B[a]PDE)-DNA adduct
      formation (adduct induced by the ultimate carcinogenic metabolite of B[a]P) in
      lymphomonocytes of subjects environmentally exposed to low doses of polycyclic
      aromatic hydrocarbons (PAHs) (B[a]P). Our study population consisted of 585
      Caucasian subjects, all municipal workers living in North-East Italy and
      recruited during their periodic check-ups after informed consent. PAH (B[a]P)
      exposure was assessed by questionnaire. Anti-B[a]PDE-DNA levels were measured by
      HPLC fluorescence analysis. We found that cigarette smoking (smokers (22%) versus
      non-smokers, p<0.0001), dietary intake of PAH-rich meals (> or =52 (38%) versus
      <52 times/year, p<0.0001), and outdoor exposure (> or =4 (19%) versus <4h/day;
      p=0.0115) significantly influenced adduct levels. Indoor exposure significantly
      increased the frequency of positive subjects (> or =0.5 adducts/10(8)
      nucleotides; chi(2) for linear trend, p=0.051). In linear multiple regression
      analysis the major determinants of increased DNA adduct levels (ln values) were
      smoking (t=6.362, p<0.0001) and diet (t=4.035, p<0.0001). In this statistical
      analysis, indoor and outdoor exposure like other factors of PAH exposure had no
      influence. In non-smokers, the influence of diet (p<0.0001) and high indoor
      exposure (p=0.016) on anti-B[a]PDE-DNA adduct formation became more evident, but
      not that of outdoor exposure, as was confirmed by linear multiple regression
      analysis (diet, t=3.997, p<0.0001 and high indoor exposure, t=2.522, p=0.012).
      This study indicates that anti-B[a]PDE-DNA adducts can be detected in the general
      population and are modulated by PAH (B[a]P) exposure not only with smoking -
      information already known from studies with limited number of subjects - but also
      with dietary habits and high indoor exposure. In non-smokers, these two factors
      are the principal determinants of DNA adduct formation. The information provided
      here seems to be important, since DNA adduct formation in surrogate tissue is an
      index of genotoxic exposure also in target organs (e.g., lung) and their increase
      may also be predictive of higher risk for PAH-related cancers.

PMID- 16978914
TI  - In vivo micronucleus test with flow cytometry after acute and chronic exposures
      of rats to chemicals.
AB  - The use of flow cytometry with rat peripheral blood erythrocytes is expected to
      increase the sensitivity of the in vivo micronucleus test and allows assessment
      of the genotoxic effects at doses that may be equal or close to those relevant to
      human exposure. However, there was a limitation to the use of rat peripheral
      blood erythrocytes since the spleen selectively removes micronucleated
      erythrocytes from circulation. In the present study, the selective analysis by
      flow cytometry of young MN-PCEs (micronucleated polychromatic erythrocytes or
      reticulocytes) by use of anti-CD71 antibodies was intended to compensate for the
      splenic clearance of micronucleated erythrocytes. The young polychromatic
      erythrocytes have on their surface a specific marker (CD71 antigen) that
      decreases in density during the maturation process. To investigate the usefulness
      of the flow cytometric micronucleus analysis combined with anti-CD71 staining of
      reticulocytes several compounds were tested in acute or sub-chronic treatment
      regimens. Furthermore, an evaluation was conducted in comparison with the
      standard rat bone-marrow micronucleus test with additional compounds. The results
      of acute studies with intraperitoneal application of ethyl methanesulfonate (EMS)
      (50, 100 and 200 mg/kg) and mitomycin C (MMC) (0.5, 1 and 2 mg/kg), were
      comparable to data published in the literature. Sub-chronic experiments were
      performed with cyclophosphamide (CP) (1, 2, 4 and 8 mg/(kg day)), colchicine (6,
      8 mg/(kg day)) and mitomycin C (0.1 mg/(kg day)) and showed dose- and time
      dependent accumulation of MN-PCEs. Parallel analysis of micronucleus induction in
      peripheral blood and bone marrow performed with Novartis compounds up to the
      highest tested dose (5 mg/kg of compound A, 200 mg/kg of compound B and 1250
      mg/kg of compound C) showed concordant results. Furthermore, we performed kinetic
      studies of micronucleus induction in peripheral blood samples obtained at various
      times after a single treatment with 10 mg/kg CP and with 6 or 8 mg/kg of
      colchicine. Such experiments gave important supplementary information about the
      time course of micronucleus induction. Our data suggest that the peripheral blood
      flow-cytometry micronucleus test can be used for the assessment of micronucleus
      induction after acute and chronic exposures of rats to chemicals.

PMID- 16978915
TI  - The relationship between micronuclei in human lymphocytes and selected
      micronutrients in vegetarians and non-vegetarians.
AB  - A vegetarian diet results in higher intake of vitamins and micronutrients, which 
      although providing antioxidant defence - may lead to deficiency in other
      micronutrients involved in DNA metabolism and stability (such as vitamins
      belonging to the B group). The principal difference among various vegetarian
      diets is the extent to which animal products are avoided. We have performed a
      pilot study to determine the relationship between the micronucleus frequency in
      lymphocytes and diet, and we compared the levels of Vitamins C and E, beta
      carotene, B(12), folic acid, homocysteine and total antioxidant capacity in
      healthy vegetarians and non-vegetarians. The vegetarian group, consisting of 24
      volunteers (13 women and 11 men), were matched for age and sex with 24 volunteers
      (12 women and 12 men) with a traditional dietary habit. Among the vegetarians
      were 13 lacto-ovo-vegetarians with average duration of vegetarian diet 10.8 years
      (ranging from 5 to 26 years) and 11 lacto-vegetarians with average duration of
      vegetarian diet 8.2 years (ranging from 3 to 15 years). Homocysteine, Vitamins C
      and E and beta-carotene levels in plasma were assayed by HPLC, and serum folate
      and Vitamin B(12) were determined with Elecsys Immunoassay tests. The total
      antioxidant capacity of plasma was estimated by measuring the ferric-reducing
      activity in a spectrophotometric assay. Micronuclei were measured in cytokinesis
      blocked lymphocytes. Vegetarians had significantly higher levels of Vitamin C and
      beta-carotene (but not Vitamin E) in plasma compared with non-vegetarians
      (P<0.001). There were no significant differences in serum levels of folic acid
      and Vitamin B(12) between the monitored groups. Levels of folic acid in
      vegetarians correlated with length of vegetarianism (r=0.62, P=0.001, N=24).
      Vegetarians had elevated levels of homocysteine compared with non-vegetarians
      (P=0.007), as did vegetarian women compared with non-vegetarian women (P=0.031).
      We did not find any differences in total antioxidant capacity or in micronucleus
      frequency between the groups. Micronuclei correlated with age (r=0.62, P<0.001,
      N=48), women having higher frequencies than men. Multifactorial regression
      analysis showed significant effects of age, sex and total antioxidant capacity on
      micronucleus frequency (N=48, P<0.001).

PMID- 16978916
TI  - Squamous cell carcinoma as a rare entity of primary liver tumor with grave
      prognosis.
AB  - The development of primary squamous cell carcinoma (SCC) of the liver has only
      rarely been reported in association with pre-existing hepatic cysts and biliary
      tract diseases. This report describes an unusual case of SCC originating in a
      cirrhotic liver. A 63-year-old male alcoholic was incidentally found to have a 6
      cm liver tumor which showed mixed echogenic by sonography and a low-density area
      with rim enhancement by computed tomography. Tumor biopsy led to a diagnosis of
      SCC with a sarcomatoid change. The tumor showed fatal rapid growth accompanied by
      abdominal pain. Transcatheter arterial embolization and chemotherapy were not
      effective, and the tumor increased to 13cm in diameter over an 8-month period. A
      post-mortem search revealed no alternative primary tumor site other than liver.
      Review of the literature shows that abdominal pain is a chief symptom of primary
      liver SCC. Only three of the nine patients treated with hepatic resection
      survived without recurrence during 8 months to 4 years of follow-up. We propose
      that SCC with a grave prognosis should be considered as a rare entity of primary
      liver tumor even in cirrhotic patients.

PMID- 16978917
TI  - Chronic fatigue syndrome.
AB  - Chronic fatigue syndrome (CFS) is thought to have a worldwide prevalence of 0.4
      1% with approximately 240,000 patients in the UK. Diagnosis is based on clinical
      criteria and critically depends on exclusion of other physical and psychiatric
      diseases. Studies of pathogenesis have revealed immune system abnormalities and
      chronic immune activation, dysfunction of the hypothalamic-pituitary-adrenal
      (HPA) axis, brain abnormalities, evidence of emotional stress (comprising host
      aspects) and evidence of exogenous insults, for example, various microbial
      infections (Epstein-Barr virus, enteroviruses, parvovirus B19, Coxiella burnetii
      and Chlamydia pneumoniae), vaccinations and exposure to organophosphate chemicals
      and other toxins (comprising environmental aspects). Emotional stress appears to
      be very important as it reduces the ability of the immune system to clear
      infections, it's presence has been shown to determine whether or not an
      individual develops symptoms upon virus infection, and it leads to activation of
      the HPA axis. But, emotional stress is distinct from depression, the presence of
      which precludes a diagnosis of CFS. There is no specific treatment for CFS other
      than the much underutilised approach of specific treatment of virus infections.
      Current priorities are to understand the molecular pathogenesis of disease in
      terms of human and virus gene expression, to develop a diagnostic test based on
      protein biomarkers, and to develop specific curative treatments.

PMID- 16978918
TI  - Clinical utility of CMV early and late transcript detection with NASBA in
      bronchoalveolar lavages.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection can cause severe disease in
      immunocompromised individuals, with CMV pneumonia, most commonly seen in lung or
      bone marrow transplant recipients, carrying a particularly high fatality rate.
      Early and accurate diagnosis of CMV pneumonia is therefore critical. OBJECTIVES:
      Current diagnostic tests for CMV pneumonia in bronchoalveolar lavage (BAL)
      specimens are either insensitive or poor prognostic indicators of disease. We
      therefore examined nucleic acid sequence-based amplification (NASBA) assays for
      CMV transcripts in BAL for the prediction of CMV pneumonia and associated
      diseases. STUDY DESIGN: A total of 220 BAL specimens from lung transplant
      recipients and other patients with suspected viral pneumonia were studied. Ninety
      nine samples had previously tested positive for CMV by shell vial (SV) culture,
      while the other 121 had tested negative. All specimens were assayed for CMV pp67
      and immediate early (IE) transcripts by NASBA. Results were correlated with
      evidence of concurrent or subsequent CMV pneumonia, rejection, and infection with
      other microbes. RESULTS: From a total of 220 BAL specimens, 27 tested positive
      for pp67 mRNA, 25 tested positive for IE mRNA, and 17 tested positive for both.
      Only 10 specimens tested positive for CMV by either or both NASBA assays while
      testing negative by SV assay. However, 74 specimens were SV positive but negative
      in both NASBA assays. Detection of CMV by any of the three methods was associated
      with an increased prevalence of pneumonia (i.e., pulmonary interstitial
      inflammation with radiographic or clinical evidence of lung injury), but not with
      pulmonary CMV pathology. Detection of CMV by SV was associated with moderate to
      severe graft rejection. There was no evidence of increased bacterial or fungal
      pulmonary infections associated with a positive CMV result by any of the three
      assays. CONCLUSIONS: Detection of either CMV pp67 or IE mRNA transcripts by NASBA
      in BAL specimens can occasionally identify CMV infections that are negative by
      conventional shell vial culture, but does not have sufficient sensitivity or
      positive predictive value to be employed routinely for pre emptive management of
      pulmonary CMV disease in transplant recipients.

PMID- 16978919
TI  - Control of phospholipase A2 activities for the treatment of inflammatory
      conditions.
AB  - Phospholipase-A2 (PLA2) enzymes hydrolyze cell membrane phospholipids to produce
      arachidonic acid (AA) and lyso-phospholipids (LysoPL), playing a key role in the
      production of inflammatory lipid mediators, mainly eicosanoids. They are
      therefore considered pro-inflammatory enzymes and their inhibition has long been
      recognized as a desirable therapeutic target. However, attempts to develop
      suitable PLA2 inhibitors for the treatment of inflammatory diseases have yet to
      succeed. This is due to their functional and structural diversity, and their
      homeostatic and even anti-inflammatory roles in certain circumstances. In the
      present review we outline the diversity and functions of PLA2 isoforms, and their
      interplay in the induction and inhibition of inflammatory processes, with
      emphasis on discussing approaches for therapeutic manipulation of PLA2
      activities.

PMID- 16978920
TI  - Memory guided saccades in mesial temporal lobe epilepsy with hippocampal
      sclerosis.
AB  - OBJECTIVE: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) may
      involve extrahippocampal areas of structural and functional damage. The incidence
      and the features of this damage are still a matter of debate and vary depending
      on the method applied. Memory guided saccades (MGSs) with a memorization delay
      longer than 20s can be used reliably to evaluate the parahippocampal cortex.
      METHODS: MGSs with 3 and 30s memorization delays were recorded with the search
      coil technique in six patients affected by right MTLE-HS, and in 13 healthy
      controls. RESULTS: The patients were not able to reduce the MGSs residual
      amplitude error after the first saccade with a 30s memorization delay. This
      finding was more evident with leftward saccades. CONCLUSIONS: MGS abnormalities
      suggested the functional involvement of the right parahippocampal cortex in most
      of the patients with MTLE-HS, and this supports the clinical and
      anatomopathological heterogeneity of the disease. SIGNIFICANCE: MGSs can be used
      in patients with right MTLE-HS to detect a possible functional involvement of the
      ipsilateral parahippocampal cortex.

PMID- 16978921
TI  - The diagnostic accuracies of chronic obstructive pulmonary disease (COPD) in
      general practice: The results of the MAGIC (Manchester Airways Group Identifying
      COPD) study.
AB  - BACKGROUND: Although it is generally accepted that chronic obstructive pulmonary
      disease (COPD) is underdiagnosed, there is little objective information
      concerning the size of the problem in the UK. METHOD: Patients from two general
      practices were offered spirometry if they were aged 30 or older, had reported
      ever smoking in one of four postal respiratory surveys (1993-2001), and/or
      reported four or more symptoms or risk factors in 2001 indicating likely
      obstructive airways disease. RESULTS: Of 2646 subjects invited, 871 attended and
      825 had adequate spirometry results for analysis. In all, 163 patients had
      spirometrically-confirmed COPD; 103 of these (63.2%) had no recorded COPD in
      their practice records, including 14 out of 31 (45.2%) whose spirometry results
      classified them as having severe or very severe COPD. CONCLUSION: This study
      found a considerable under-recording of COPD in two general practices. This may
      be due to a combination of administrative and diagnostic problems (including the
      under-use of spirometers), and a reluctance of patients to present with their
      symptoms. These results have important implications in terms of unmet need and
      resource utilisation.

PMID- 16978923
TI  - Chronic obstructive pulmonary disease in Brazilian primary care: Diagnostic
      competence and case-finding.
AB  - AIMS: The developing world is particularly at risk of an increasing health burden
      due to an increased prevalence of Chronic Obstructive Pulmonary Disease (COPD)
      secondary to increasing tobacco consumption. However, research is scarce. The
      objectives of this study were to assess the current competence for diagnosing
      COPD in primary care in a resource-limited setting in Brazil, and to develop a
      local patient profile for case-finding. METHODS: 34 general practitioners (GPs)
      in five areas of northern Brazil recruited adult patients with principal
      complaints of cough and/or shortness of breath who then had spirometry (n = 142).
      RESULTS: For the dichotomous variable 'COPD' the degree of agreement between GP
      diagnosis (n = 64, 18.3%) and spirometric outcome (n = 36, 25.4%) was poor, with
      Kappa = 0.055 (SE 0.087) and DOR = 1.35. False-positive and false-negative
      diagnosis proportions were 19.8% and 75%, respectively. Independent risk factors
      were 'smoking history of more than five pack years' and 'presence of both
      dyspnoea and cough'. It requires the testing of 2.2 smokers with more than five
      pack years to detect one patient at risk. CONCLUSIONS: COPD is a common yet
      underdiagnosed disease in Brazilian primary care. Spirometry improves diagnostic
      competence and case-finding substantially. If applied in a pre-selected high-risk
      population, we believe spirometry can be a cost-effective diagnostic tool for
      case-finding in the resource-limited setting. This study provides important
      baseline information for effective guideline implementation.

PMID- 16978924
TI  - Effect of example weights on prediction of protein-protein interactions.
AB  - Protein-protein interactions (PPIs) prediction is an important issue in biology.
      Recently many computational methods have been proposed to determine PPIs.
      However, there is no golden standard dataset for these methods now. Furthermore,
      there exists different quality among training examples and the quality is always
      ignored by the current methods. In the condition of low-quality examples, the
      system should tolerate the data noise. Example weighting strategy is used in this
      paper to build a robust system and solve the problem of data noise. Training
      examples are investigated and a new example selecting/using strategy is proposed.
      Training example weighting method based on confidence is proposed. Different
      weight setting strategies are discussed and the corresponding results are given
      in the experiment. A new model integrating example weighting strategy, attraction
      repulsion (AR) weight model, is proposed. Experimental results on Saccharomyces
      cerevisiae demonstrate that the new model outperforms the original AR model in
      the ROC score measure by over 8%. Furthermore, the example weighting strategy is
      applied to another domain-based PPIs prediction method, maximum likelihood
      estimation (MLE) method, and the modified MLE method obtains better performance
      than the original MLE method. At same time, our examples weighting strategy can
      be applied to any other training example based PPIs prediction methods.

PMID- 16978925
TI  - Verbal memory impairment in children with focal epilepsy.
AB  - Findings of both material- and hemisphere-specific influence on memory
      performance in children with epilepsy are inconsistent. Verbal memory of 80
      children with focal epilepsy, aged 7 to 16, was assessed and compared with verbal
      memory of 80 healthy schoolchildren. The Verbal Selective Reminding test was used
      to distinguish between patients with left-sided (N=38) and patients with right
      sided (N=42) electroencephalographic focal abnormalities. In addition, groups
      with temporal (N=36) and extratemporal (N=44) focal epilepsy were compared.
      Effects of seizure-related variables were also assessed. Children with focal
      epilepsy scored significantly lower on tests when compared with the healthy
      group. Lateralization of the EEG focus was not found to significantly affect
      verbal memory performance. Only the CLTR component of the Verbal Selective
      Reminding test was susceptible to lateralization and localization effects.
      Differences between the group with left and the group with right temporal
      epilepsy (P<0.03) and between the group with temporal and the group with
      extratemporal epilepsy (P<0.01) reached statistical significance.

PMID- 16978926
TI  - Wave reflection analysis of the human cerebral circulation during syncope.
AB  - Up till now, the presence of wave reflection of pressure and flow waves was not
      considered in studies on the cerebral circulation. This study tested the
      hypothesis whether the typical changes in cerebral blood flow velocity (CBFV)
      seen in patients during vasovagal syncope can be explained by the emergence of a
      wave reflection site in the cerebrovascular vessels. Continuous recordings of
      peripheral blood pressure (ABP, by Finapres) and CBFV (by transcranial Doppler)
      of 20 control subjects and 10 patients with syncope during tilt table testing
      were analyzed. Wave reflection analysis (WRA) consisted of a multivariate
      regression analysis with CBFV as dependent variable and simultaneous ABP as well
      as delayed ABP (by systematically varied time lags) as independent variables. The
      time delay yielding the best prediction of CBFV was interpreted as the reflection
      time. A univariate regression analysis with only simultaneous ABP as independent
      variable served as control method. In patients and controls CBFV during supine
      position could be explained sufficiently (explained variance=88-90%) by
      univariate regression without improvement by WRA. During syncope, multivariate
      regression improved the prediction of CBFV (explained variance=58% with
      univariate and 77% with multivariate regression) in 9 of 10 patients. The mean
      reflection time was 160 ms. The results can be explained by a collapse of the
      distal bridging veins during systemic hypotension giving rise to a pressure wave
      moving backward with a resulting distortion of the flow wave. In particular, the
      WRA model could account for the characteristic changes in the diastolic flow
      shape during syncope.

PMID- 16978927
TI  - Endogenous endothelins and the response to electrical renal nerve stimulation in
      anaesthetized rabbits.
AB  - The influence of endogenous endothelins on the neural control of renal function
      is poorly understood. We therefore studied the effects of endothelin blockade
      (combined ET(A) and ET(B) receptor antagonism using TAK-044) on the acute and
      prolonged effects of renal nerve stimulation in rabbits, measuring renal blood
      flow, glomerular filtration rate (GFR), urine flow and sodium excretion. Brief (3
      min) stimulation over 0.5-8 Hz produced frequency-dependent reductions in total
      renal blood flow, cortical blood flow and, less markedly, medullary blood flow.
      TAK-044 did not significantly alter basal total renal blood flow or cortical
      blood flow, or their responses to nerve stimulation, but significantly increased
      basal medullary blood flow (P<0.01) and increased the slope of the stimulation
      frequency-medullary blood flow relationship (P<0.05). Prolonged (20 min)
      stimulation at 0, 0.5 and 2 Hz produced frequency-dependent reductions in total
      renal blood flow, GFR, urine flow and sodium excretion, but not medullary blood
      flow. Pretreatment with TAK-044 did not significantly alter these responses.
      Thus, endogenous endothelins do not appear to either augment or lessen the
      effects of renal nerve activation on total renal blood flow, cortical blood flow,
      GFR or sodium excretion. The apparent ability of TAK-044 to enhance medullary
      blood flow responses to renal nerve stimulation may reflect an action of
      endogenous endothelins to blunt neurally mediated vasoconstriction in the
      medullary circulation. Alternatively, it may simply be secondary to the effects
      of endogenous endothelins on basal medullary blood flow.

PMID- 16978928
TI  - Electrochemical response of oligonucleotides on carbon paste electrode.
AB  - Electrochemical response of synthetic oligonucleotides with different DNA bases
      sequences was investigated to find relationships between a chain composition and
      a signal. All DNA mononucleotides present electroactivity at a carbon paste
      electrode yielding anodic peaks at potentials: 1.00 (GMP), 1.28 (AMP), 1.47 (TMP)
      and 1.53 V (CMP). Also 15-mer homooligonucleotides show respective anodic peaks.
      Electrochemical response of 15- and 19-mer oligonucleotides consisting of all
      four DNA bases in different amounts was determined by the composition of
      oligonucleotide chain. When the contribution of different bases in
      oligonucleotide was balanced two anodic peaks were obtained that can be
      attributed to guanine and adenine moieties. Thymine residue is shown as a
      separate peak in voltammogram when its content in oligonucleotide chain is close
      to 50% of the total number of bases. Cytosine also yields a peak at its
      significant contribution in oligonucleotide chain and both pyrimidinic moieties
      produce catalytic waves easier when one of them is dominating or when only one
      pyrimidine derivative is present in a chain. Guanine is the easiest oxidized base
      and it produces a peak even at its minimal contribution (one guanine residue in
      19-mer oligonucleotide). Guanine peak potential is dependent on oligonucleotide
      concentration and oligonucleotide composition. The lowest oligonucleotide
      concentration detected by guanine peak was 12.5 nM whereas detected by thymine
      peak was 90 nM.

PMID- 16978929
TI  - Major oxidative products of cytosine are substrates for the nucleotide incision
      repair pathway.
AB  - Most common point mutations occurring spontaneously or induced by ionizing
      radiation are C-->T transitions implicating cytosine as the target. Oxidative
      cytosine derivatives are the most abundant and mutagenic DNA damage induced by
      oxidative stress. Base excision repair (BER) pathway initiated by DNA
      glycosylases is thought to be the major pathway for the removal of these lesions.
      However, in alternative nucleotide incision repair (NIR) pathway the
      apurinic/apyrimidinic (AP) endonucleases incise DNA duplex 5' to an oxidatively
      damaged base in a DNA glycosylase-independent manner. Here, we characterized the
      substrate specificity of human major AP endonuclease, Ape1, towards 5-hydroxy-2'
      deoxycytidine (5ohC) and alpha-anomeric 2'-deoxycytidine (alphadC) residues. The
      apparent kinetic parameters of the reactions suggest that Ape1 and the DNA
      glycosylases/AP lyases, hNth1 and hNeil1 repair 5ohC with a low efficiency.
      Nevertheless, due to the extremely high cellular concentration of Ape1, NIR was
      the major activity towards 5ohC in cell-free extracts. To address the
      physiological role of NIR function, we have characterized naturally occurring
      Ape1 variants including amino acids substitutions (E126A, E126D and D148E) and N
      terminal truncated forms (NDelta31, NDelta35 and NDelta61). As expected, all Ape1
      mutants had proficient AP endonuclease activity, however, truncated forms showed
      reduced NIR and 3'-->5' exonuclease activities indicating that these two
      functions are genetically linked and governed by the same amino acid residues.
      Furthermore, both Ape1-catalyzed NIR and 3'-->5' exonuclease activities generate
      a single-strand gap at the 5' side of a damaged base but not at an AP site in
      duplex DNA. We hypothesized that biochemical coupling of the nucleotide incision
      and exonuclease degradation may serve to remove clustered DNA damage. Our data
      suggest that NIR is a backup system for the BER pathway to remove oxidative
      damage to cytosines in vivo.

PMID- 16978930
TI  - Exhaled nasal nitric oxide output is reduced in humans at night during the sleep
      period.
AB  - The physiologic function of nasal nitric oxide (NO) release is unknown. In prior
      experiments, topical NG-nitro-L-arginine methyl ester (L-NAME) on nasal mucosa
      reduced exhaled nasal NO output and caused daytime sleepiness. We hypothesized
      that nasal NO output is reduced at night during the sleep period. We measured
      exhaled nasal NO concentration and minute ventilation and calculated nasal NO
      output in humans over 24 h. Daytime awake NO output was greater than NO output at
      night during sleep or transient wakefulness. Exhaled NO concentration decreased
      during sleep along with minute ventilation. A daytime voluntary reduction in
      minute ventilation also decreased nasal NO output but exhaled NO concentration
      increased. Nasal NO output was not changed by body position. We conclude that
      exhaled nasal NO output is decreased at night due to decreased mass flow of NO
      into nasal air in addition to decreased minute ventilation. Our findings suggest
      a role of nasal NO in sleep or in the physiologic processes accompanying sleep.

PMID- 16978931
TI  - Studies on the toxicological detection of the designer drug 4-bromo-2,5-dimethoxy
      beta-phenethylamine (2C-B) in rat urine using gas chromatography-mass
      spectrometry.
AB  - The phenethylamine-derived designer drug 4-bromo-2,5-dimethoxy-beta
      phenethylamine (2C-B) is known to be extensively metabolized in various species
      including humans. In rat urine, 2C-B was found to be excreted mainly via its
      metabolites. In the current study, the toxicological detection of these
      metabolites in the authors' systematic toxicological analysis (STA) procedure was
      examined. The STA procedure using full-scan GC-MS allowed proving an intake of a
      common drug abusers' dose of 2C-B by detection of the O-demethyl deaminohydroxy
      and two isomers of the O-demethyl metabolites in rat urine. Assuming similar
      metabolism, the described STA procedure should be suitable for proof of an intake
      of 2C-B in human urine.

PMID- 16978932
TI  - Separation and quantitative analysis of alkyl sulfobetaine-type detergents by
      high-performance liquid chromatography and light-scattering detection.
AB  - An improved high-performance liquid chromatographic (HPLC) method for the
      separation of zwitterionic detergents is described. It is based on a reversed
      phase liquid chromatography with evaporative light-scattering detection (ELSD).
      The method was shown to be highly specific, allowing the separation of three
      detergents of the alkyl sulfobetaine family: 3-(N-dodecyl-N,N-dimethyl-ammonio)
      propane-1-sulfonate (SB12), 3-(N-tetradecyl-N,N-dimethyl-ammonio)-propane-1
      sulfonate (SB14) and 3-(N-hexadecyl-N,N-dimethyl-ammonio)-propane-1-sulfonate
      (SB16). It was further used to develop a quantitation method for SB14, which was
      validated for linearity, precision, robustness, limits of detection and
      quantitation, specificity and accuracy. Linearity was found in the range of 50
      500 microg/ml with a correlation coefficient of 0.9938+/-0.0029. The mean value
      of slope and intercept were 1.567+/-0.06 and 0.1541+/-0.0271, respectively. The
      limits of detection (LOD) and quantitation (LOQ) were 2 and 10 microg/ml,
      respectively. The validated method was used to determine the concentration of
      SB14 in different biological samples, specially in bulks of a recombinant
      membrane protein, the Klebsiella pneumoniae outer membrane protein A, which is
      produced at the pilot scale for human clinical studies.

PMID- 16978933
TI  - Determination of soyasaponins Ba and Bb in human serum by high-performance liquid
      chromatography coupled with electrospray ionization tandem mass spectrometry.
AB  - A rapid, sensitive and selective high-performance liquid chromatography-tandem
      mass spectrometric method (HPLC-MS-MS) has been developed and validated for the
      determination of soyasaponins Ba and Bb in human serum using glycyrrhizin as
      internal standard (I.S.). Soyasaponins Ba and Bb were extracted from human serum
      by liquid-liquid extraction and cleaned up by C(18) solid-phase extraction (SPE),
      followed by separation on a C(18) reversed-phase column using acetonitrile/water
      containing 0.025% acetic acid as a mobile phase for gradient elution.
      Soyasaponins Ba and Bb, and I.S. were ionized by negative ion pneumatically
      assisted electrospray and detected by HPLC-MS-MS in the multiple-reaction
      monitoring (MRM) mode using precursor-->product ion combinations at m/z 958-
      >940, 942-->924 and 822-->351, respectively. The calibration curves were linear
      (r(2)>0.991) in the concentration range of 0.5-100.0 ng/mL, with lower limits of
      quantification of 0.5 and 0.3 ng/mL for soyasaponins Ba and Bb, respectively, in
      human serum. Intra-day and inter-day relative standard deviations (R.S.D.) were
      less than 7.9 and 11.3%, respectively. The mean recoveries of soyasaponins Ba and
      Bb ranged from 92 to 101% and from 85 to 94%, respectively.

PMID- 16978934
TI  - Analysis of cephalosporins in bronchial secretions by capillary electrophoresis
      after simple pretreatment.
AB  - The applicability of capillary zone electrophoresis (CZE) for analysis of
      cephalosporin antibiotics has been studied in bronchial secretion as highly
      viscous, thick and non-homogeneous samples. The lyophilization was found to be a
      simple but effective pretreatment of these samples to bring them into a form
      which is suitable for injection to CE capillary. The obtained good recovery data
      prove that the lyophilization/dissolution of bronchial secretion samples can be
      reproducibly performed.

PMID- 16978935
TI  - Push-and-pull enteroscopy using the double-balloon technique/double-balloon
      enteroscopy.
AB  - Push-and-Pull enteroscopy/Double balloon enteroscopy (PPE/DBE) allows enteroscopy
      of the entire small bowel, or at least a substantial part of it. The complication
      rate is acceptably low. Severe complications such as pancreatitis and perforation
      were encountered in the literature in approximately 1% of all diagnostic
      PPE/DBEs. It can be expected that the complication rate of therapeutic PPE/DBEs
      is higher, comparable with the conventional endoscopy. The diagnostic yield is
      high, at approximately 75%, as is the therapeutic yield. The option of carrying
      out endoscopic therapy (in approximately 40%-50% of cases in the Western
      hemisphere) is an important aspect. Angiodysplasias are the main bleeding source,
      at least in Western countries. Using the PPE/DBE device, endoscopic treatments
      such as endoscopic hemostasis using injection and argon plasma coagulation,
      polypectomy, endoscopic resection, balloon dilation, and foreign-body extraction
      have become feasible even in the small intestine and can generally be performed
      safely and without relevant technical problems. Medical therapy can be started in
      up to 20% of cases-e.g., after a new or changed diagnosis of Crohn's disease.
      Surgical therapy is required in 10-20% of cases, due to malignant tumors or
      complex stenoses, for example. The main indication is mid-gastrointestinal
      bleeding.

PMID- 16978936
TI  - Neonatal SEP - back to bedside with basic science.
AB  - Scalp-recorded somatosensory evoked potentials (SEPs) have been successfully used
      in neonatal assessment for several decades. The current routine SEP paradigm is
      markedly predictive for future cerebral palsy (CP) or other neurocognitive
      sequelae in brain-injured babies. Recent advances in basic science have
      dramatically increased our knowledge about structural-functional development of
      SEP-related brain mechanisms. It has thereby become apparent that preterm SEP
      differs from that in more mature counterparts in that it also comprises responses
      from transient brain structures, and hence being unique to the preterm period. It
      is now obvious also that several aspects in the current SEP paradigm, ranging
      from the type of stimulation to the methods of recording and analysis, are
      suboptimal for preterm babies. Recent progress in recording and analysis
      techniques have made it possible to combine SEP studies with EEG recordings, as
      well as to implement advanced analyses (e.g. time-frequency analysis) into
      routine practice. This review summarizes literature from relevant areas in basic
      science, and proposes a novel, integrated approach in neonatal SEP studies in
      order to significantly increase the fidelity of testing somatosensory system.

PMID- 16978937
TI  - Erk pathways negatively regulate matrix mineralization.
AB  - Skeletal mineralization is an important step regulating the mechanical properties
      of the calcified tissues, but molecular events underlying mineralization still
      remain elusive. We examined the role of extracellular signal-regulated kinase
      (Erk) pathways in matrix mineralization of osteogenic cells both in vitro and in
      vivo. Matrix mineralization by preosteocytic MLO-A5 cells and osteoblastic MC3T3
      E1 cells was increased by either PD98059 Mek inhibitor treatment or adenovirus
      vector-mediated dominant negative Ras (Ras(DN)) expression and was suppressed by
      Erk activation by platelet-derived growth factor (PDGF) treatment or
      constitutively active Mek1 (Mek(CA)) expression. Administration of adenovirus
      vectors carrying Ras(DN) gene onto the calvaria of 1-day-old mice increased the
      mineralization of the tissues, while that of the Mek(CA) adenovirus suppressed
      it. These results suggest that the Erk pathway is a negative regulator of the
      matrix mineralization both in vitro and in vivo.

PMID- 16978938
TI  - Increase of bone volume by a nanosecond pulsed laser irradiation is caused by a
      decreased osteoclast number and an activated osteoblasts.
AB  - The biostimulatory effects of laser irradiation focus not only in the field of
      soft tissue but also bone formation. Studies have shown that the light of a
      nanosecond pulsed laser which has a high peak power can produce stress waves in
      tissue. We have hypothesized that nanosecond pulsed laser irradiation stimulates
      bone formation. Our aim was to clarify the mechanism of increased bone volume by
      nanosecond pulsed laser irradiation. Rat femur was irradiated with a Q-switched
      Nd:YAG laser, which has a wavelength of 1064 nm. The quantification of trabecular
      architecture using three-dimensional morphometric analysis and measurement of
      bone mineral density (BMD) using pQCT was performed on day 1, day 3, day 5, and
      day 7 after laser irradiation. The laser effects on bone cells were also
      investigated using histological and immunohistochemical analysis. On day 1 after
      laser irradiation, bone volume (BV/TV), trabecular thickness (Tb.Th), and other
      parameters of the irradiated group did not significantly differ from the non
      irradiation group (control). However, the mean BV/TV, Tb.Th, mineral apposition
      rate, and BMD of the laser group on day 7 after laser irradiation were
      significantly greater than those of the control. On histological analysis, the
      number of TRAP-positive osteoclasts was lower on day 3 after laser irradiation.
      Osteoblasts with activated clearance were seen in the laser irradiated group on
      day 1 and day 3. These data reveal that the increased bone volume by nanosecond
      pulsed laser irradiation causes an increase in osteoblast activity and a decrease
      in osteoclast number.

PMID- 16978939
TI  - Compassion and communication in cancer care.

PMID- 16978940
TI  - Breast cancer-specific mortality after invasive local recurrence in patients with
      ductal carcinoma-in-situ of the breast.
AB  - BACKGROUND: Previous studies on the efficacy of primary treatments for ductal
      carcinoma-in-situ (DCIS) have focused on local recurrence rates. Our objective
      was to detail the outcomes of local invasive recurrence, distant recurrence, and
      breast cancer mortality in patients previously treated for DCIS. METHODS:
      Clinical, pathologic, and outcome data were collected prospectively for 1236
      patients with pure DCIS accrued from 1972 through 2005. RESULTS: There were 150
      recurrences (87 DCIS and 63 invasive). Invasive local recurrence after mastectomy
      was rare (0.5% of patients) and after breast preservation was more frequent
      (12.0% of patients). The 12-year probabilities of breast cancer-specific
      mortality after mastectomy and after breast preservation were 0.8% and 1.0%,
      respectively. The 12-year breast cancer-specific mortality and distant disease
      probability for the 63 patients with invasive recurrences were 12% and 15%,
      respectively. CONCLUSIONS: Regardless of initial treatment, most patients with
      invasive local recurrence after treatment for DCIS can be treated and cured.

PMID- 16978941
TI  - Margin width as the sole determinant of local recurrence after breast
      conservation in patients with ductal carcinoma in situ of the breast.
AB  - BACKGROUND: A previous study showed a 3% local recurrence risk at 8 years in
      ductal carcinoma in situ (DCIS) patients treated with excision alone with
      surgical margins of 10 mm or greater. This study updates those data. METHODS: A
      total of 272 DCIS patients treated conservatively with 10 mm or greater margins
      were reviewed in a prospective database. RESULTS: Among 212 excision-alone
      patients, there were 9 DCIS and 3 invasive recurrences. The 12-year probability
      of any local recurrence was 13.9%; of invasive recurrence it was 3.4%. Among 60
      excision plus radiation patients, there was 1 local (invasive) recurrence (P =
      .06). The 12-year probability of local recurrence was 2.5%. CONCLUSIONS: Local
      recurrence in DCIS patients treated with excision alone with margins of 10 mm or
      greater compares favorably with local recurrence in DCIS patients with
      nontransected margins and treated with postoperative radiation. The risk of
      invasive recurrence among widely excised DCIS patients is extremely low.

PMID- 16978942
TI  - Intraoperative injection of technetium-99m sulfur colloid is effective in the
      detection of sentinel lymph nodes in breast cancer.
AB  - BACKGROUND: Our objective was to determine if intraoperative injection of
      technetium-99m-labeled sulfur colloid is as effective as preoperative injection
      in the detection of sentinel lymph nodes (SLNs). METHODS: Two hundred consecutive
      patients with breast cancer underwent SLN biopsy examination. Radiocolloid was
      injected in the preoperative area (group A) or immediately after induction of
      anesthesia in the operating room (group B). RESULTS: The SLN detection rate was
      similar for groups A (96%) and B (100%; P = .2). Radioactive SLNs were detected
      in 95% of patients in group A and in 97% of patients in group B (P = .1). The
      mean number of SLNs harvested was 1.6 and 2.1 for groups A and B, respectively.
      There was no significant difference in positive SLNs between groups (P = .11).
      CONCLUSIONS: Intraoperative injection of sulfur colloid is highly effective in
      the detection of SLNs, avoiding patient discomfort and surgical schedule delays.

PMID- 16978943
TI  - Preliminary results and evaluation of MammoSite balloon brachytherapy for partial
      breast irradiation for pure ductal carcinoma in situ: a phase II clinical study.
AB  - BACKGROUND: This report presents the preliminary results and evaluation of the
      MammoSite balloon catheter (MammoSite Radiation Therapy System; Cytyc
      Corporation, Marlboro, MA) as the sole method of delivering partial breast
      irradiation to the lumpectomy bed with breast-conserving surgery in patients with
      pure ductal carcinoma in situ (DCIS). METHODS: Twelve institutions are
      participating in this phase II clinical study. A total of 133 patients have been
      enrolled and 100 patients have successfully completed the prescribed radiation
      therapy. A dose of 34 Gy was delivered in 10 fractions over 5 days prescribed to
      1 cm from the applicator surface using iridium-192 high-dose rate brachytherapy.
      Patients who met the following criteria were selected for enrollment into the
      study: age 45 years or older, unicentric pure DCIS, mammographic lesion of 3 cm
      or less, negative margins as defined by 1 mm or more, postoperative final gross
      pathologic size of tumor of 5 cm or less, clinically node negative, and a
      postlumpectomy mammogram showing the absence of any residual suspicious
      microcalcifications. The placement of the MammoSite catheter was performed either
      at the time of the lumpectomy or postlumpectomy. The minimum distance from the
      balloon surface to the surface of the skin is greater than 5 mm. Data collection
      points are at time of enrollment, time of implant, 3 months, 6 months, and then
      yearly at 1- to 5-year follow-up visits. Data collected are local control rates,
      cosmetic outcome using the Harvard Scale, toxicities, serious adverse events,
      disease-free survival, cause-specific survival, and contralateral breast failure.
      The Van Nuys Prognostic Index scores were calculated for each patient. Local
      recurrence is defined as either invasive or noninvasive recurrence within the
      target volume. Ipsilateral elsewhere recurrence is defined as either an invasive
      or noninvasive recurrence occurring outside of the target volume in the
      previously treated breast. This recurrence is classified as a new primary tumor.
      RESULTS: The mean follow-up period was 9.5 months (range, 1-24 mo). The MammoSite
      catheter was explanted for the following reasons: inadequate skin distance (5.1%;
      6 of 117), poor cavity conformance (5.1%; 6 of 117), positive margins (2.6%; 3 of
      117), final histology (.85%; 1 of 117), and physician decision (.85%; 1 of 117).
      Of the patients in whom the MammoSite was explanted because of skin spacing or
      cavity conformance, 50% were at sites of new users (institutions that have placed
      fewer than 10 Mammosite catheters). Cosmetic results were rated as excellent in
      63%, good in 35%, and fair in 2% in the 86 patients with a follow-up visit. Two
      patients were diagnosed with an ipsilateral local recurrence, 1 outside of the
      target volume and 1 true recurrence/marginal miss. One patient was diagnosed at 8
      months and the other was diagnosed at 11 months. Both of these ipsilateral
      failures were DCIS. The Van Nuys Prognostic Index of these 2 patients was 9 and
      8, respectively. Data collected showed the mean age at placement was 60.8 y, mean
      tumor size was 10.6 mm, mean actual closest surgical margin was 6.8 mm (range, .1
      40 mm), a re-excision rate of 35%, postlumpectomy placement was 71%, and the mean
      skin-to-balloon surface distance was 13 mm with 89% > or =7 mm. No serious
      adverse events were reported. The infection rate was 4.0%. CONCLUSIONS:
      Accelerated partial breast irradiation delivered with the MammoSite balloon was
      clinically successful in patients entered into a phase II clinical study with
      pure DCIS, with results comparable with other studies reported in the literature
      that have evaluated use of the MammoSite balloon brachytherapy for delivery of
      radiation therapy in early breast cancers. Inadequate skin distance and poor
      cavity conformance were the main factors limiting the use of the MammoSite
      device. Cosmetic results were good to excellent in 98%. There have been 2
      ipsilateral breast recurrences.

PMID- 16978944
TI  - A novel approach to T classification in tumor-node-metastasis staging of breast
      cancer.
AB  - BACKGROUND: The aim of this study was to examine the effect of measurement bias
      in breast cancer and to create a more rational T-size categorization in tumor
      node-metastasis staging in response to smaller, screen-detected cancers and
      measurement bias. METHODS: From 1987 to 2003, 10,853 invasive nonmetastatic
      breast cancers enlisted in the Rhode Island Cancer Registry with a known
      dimension were reviewed. Data analyzed by proposed classifications included the
      rate of lymph node metastases and the mortality rate from breast cancer. RESULTS:
      The median diameter was 16 mm. Cancer measurements reflected the bias in
      pathologists' dimension recording, which is centered strongly about whole- and
      half-centimeter sizes. A new T classification is proposed with the following
      sizes and frequencies in the Rhode Island Cancer Registry: 1 to 2 mm = T1 mic (3%
      of registered cases); 3 to 7 mm = T1a (11%); 8 to 12 mm = T1b (23%); 13 to 17 mm
      = T1c (18%); 18 to 22 mm = T2a (17%); 23 to 27 mm = T2b (8%); 28 to 32 mm = T2c
      (8%); 33 to 42 mm = T3a (6%); 43 to 52 mm = T3b (3%), and greater than 52 mm =
      T3c (4%). The unadjusted odds ratio for the probability of node metastases was
      1.43 (confidence interval, 1.40-1.46; P < .001) with each increase in proposed
      grouping. The range in the lymph node metastatic rate was 5.5% for tumors 1 to 2
      mm to 64% for cancers greater than 52 mm. By Cox proportional hazard, the
      unadjusted hazard ratio for death from breast cancer for each increase in
      proposed grouping was 1.33 (confidence interval, 1.29-1.37; P < .001). The 10
      year survival rate ranged from 98.3% for tumors 1 to 2 mm to 70.3% for cancers
      greater than 52 mm. CONCLUSIONS: A more rational T category for use in tumor-node
      metastasis staging is presented to reflect the much smaller invasive breast
      cancers encountered by screening and to account for the dimension recording bias
      of pathologists. This new T category shows a clinically and statistically
      significant linear relationship for both incidence of lymph node metastases and
      hazard ratio of death.

PMID- 16978945
TI  - A minimally invasive breast biopsy clinic: an innovative way to teach breast
      fellows how to perform breast ultrasound and ultrasound-guided breast procedures.
AB  - BACKGROUND: The ability to perform breast ultrasound and ultrasound-guided breast
      procedures are increasingly important skills for breast surgeons. Breast
      fellowship programs must develop programs to ensure adequate ultrasound training
      for breast fellows. METHODS: A Minimally Invasive Breast Biopsy Clinic was
      established at the Los Angeles County + University of Southern California Medical
      Center to provide breast fellows with comprehensive, hands-on, "live-patient"
      breast ultrasound training. RESULTS: From December 2004 though February 2005, 5
      breast fellows received training in the Minimally Invasive Breast Biopsy Clinic.
      Each fellow received a minimum of 18 weeks of "live-patient" experience. Although
      the learning curve varied among the fellows, all showed proficiency in performing
      breast ultrasound and ultrasound-guided core biopsies by the 12th week. A total
      of 39 patients with fibroadenomas underwent 62 ultrasound-guided procedures,
      including 30 vacuum-assisted percutaneous excisions, 16 cryoablations, and 16
      core biopsies. CONCLUSION: The Minimally Invasive Breast Clinic model provided
      breast fellows with sufficient "live-patient" experience to enable confident
      performance of breast ultrasound and ultrasound-guided breast procedures. The
      selection of patients with fibroadenomas facilitated safe and efficient training
      without interfering with the management of cancer patients.

PMID- 16978946
TI  - Digital documentation of the physical examination: moving the clinical breast
      exam to the electronic medical record.
AB  - BACKGROUND: Documentation of the clinical breast examination (CBE) has consisted
      of simple hand-drawings and stick figures without a common lexicon. There is a
      need for a device that can accurately depict the CBE in digital format while
      being objective, reproducible over time, and useable in the electronic medical
      record. This new device is called palpation imaging (PI). METHODS: We examined
      110 patients with a complaint of a breast mass using PI. This laptop-sized device
      creates a real-time digital display of the palpable area in both video and still
      formats. The size, hardness, shape, homogeneity, and mass location may be
      extracted from the image. RESULTS: Of those with a true mass, PI identified the
      mass in 94% while physical examination identified 86%. The positive predictive
      value (PPV) for breast cancer using PI was 94% and 78% for physical examination.
      A survey of primary care physicians revealed the inclusion of the PI record in a
      consultation note implied competence, experience, and skill by the surgeon.
      CONCLUSIONS: PI documented the CBE in a timely, efficient, and accurate manner. A
      reproducible record allows objective review by multiple examiners at varied
      times. Continued work will optimize examination methods.

PMID- 16978947
TI  - Should all breast cancers be diagnosed by needle biopsy?
AB  - BACKGROUND: Although much data support the National Quality Forum recommendation
      that breast cancers should be diagnosed by needle biopsy before surgical
      resection, the exclusion criteria for those that may not be suitable have yet to
      be defined. METHODS: We reviewed all patients treated over the past 3 years at
      the Yale Breast Center to determine the percentage of patients not diagnosed by
      needle biopsy, and why. RESULTS: Reasons for the 17% of 630 patients who were not
      diagnosed by needle biopsy were as follows: inability to cooperate (1%); small or
      superficial lesion less than 1 cm that technically was easier to excise in the
      office (4%); bloody discharge without clinical or mammographic mass (1%); lesion
      adjacent to implant (.5%); a mammographic lesion that was too posterior, too
      superficial, or too faint to be performed stereotactically (5%); or patient
      preference (5%). CONCLUSIONS: Needle biopsy is the preferred method of diagnosis
      in most cases, but there are valid reasons why all breast cancers will not be
      diagnosed in this fashion.

PMID- 16978948
TI  - What is the value of axillary dissection or sentinel node biopsy in patients with
      ductal carcinoma in situ?
AB  - BACKGROUND: Some surgeons have advocated sentinel node biopsy (SNB) for ductal
      carcinoma in situ (DCIS). The value of the information obtained is not clear.
      METHODS: From 1972 to 2005, 564 selected patients with pure DCIS had axillary
      staging with either SNB or axillary lymph node dissection (ALND). Data were
      collected in a prospective database. RESULTS: Only 2 of 564 patients had positive
      nodes by hematoxylin and eosin, and they were both in the ALND group. Both
      patients had mastectomies, were upstaged, received chemotherapy, and survived for
      more than 10 years without local or distant recurrence. Among 171 patients who
      had SNB, 10 had isolated tumor cells found by immunohistochemistry. Two patients
      who underwent SNB had local recurrence, neither developed distant or regional
      recurrence. Six of 564 patients in the ALND group developed local invasive
      recurrence and died of metastatic breast cancer, but none of them had positive
      nodes. CONCLUSIONS: Information from lymph node examination in DCIS patients
      failed to predict poor outcome. SNB is useful for DCIS in mastectomy, especially
      with immediate reconstruction. It may be indicated for DCIS at high risk for
      upgrading to invasive cancer on final excision, but reliable criteria for
      identifying these tumors are not yet available.

PMID- 16978949
TI  - Role of ultrasound-guided axillary fine-needle aspiration in the management of
      invasive breast cancer.
AB  - BACKGROUND: Previous studies from Women & Infants' Hospital have reported the
      accuracy of ultrasound-guided fine-needle aspiration biopsy examination of
      axillary lymph nodes (USFNAB) for locally advanced breast cancer. The aim of this
      article is to report our further experience with USFNAB in staging the axilla and
      determining its affect on management decisions. METHODS: We performed a
      retrospective review of prospectively collected data between January 1998 and
      June 2005. RESULTS: A total of 220 patients underwent USFNAB for breast cancer.
      Of these, 52 were excluded. Of the 168 remaining patients, 79 had positive and 89
      had negative USFNAB results. A total of 107 (63%) patients underwent primary
      surgery and 61 (37%) patients underwent neoadjuvant chemotherapy. In these
      patients, the sensitivity and specificity of USFNAB was 35% and 96% for T1, and
      67% and 100% for T2, respectively. CONCLUSIONS: The high specificity of USFNAB
      could safely eliminate sentinel lymph node biopsy examination before axillary
      lymph node dissection, particularly in T2 lesions.

PMID- 16978951
TI  - Outcomes of breast cancer in patients who use alternative therapies as primary
      treatment.
AB  - BACKGROUND: Some breast cancer patients opt for alternative treatments in place
      of conventional treatments. The lack of published data on the outcome of this
      strategy may contribute to this trend. METHODS: A chart review was performed of
      breast cancer patients who refused or delayed standard surgery, chemotherapy,
      and/or radiation therapy. Prognosis was calculated for recommended and actual
      therapy. RESULTS: Thirty-three patients were included in the analysis. Of 11
      patients who initially refused surgery, 10 developed disease progression. Of 3
      patients who refused adequate nodal sampling, 1 developed nodal recurrence. Of 10
      patients who refused local control procedures, 2 developed local recurrences and
      2 died of metastatic disease. By refusing chemotherapy, 9 patients increased
      their estimated 10-year mortality rate from 17% to 25%. CONCLUSIONS: Alternative
      therapies used as primary treatment for breast cancer are associated with
      increased recurrence and death. Homeopathy instead of surgery resulted in disease
      progression in most patients. These data may aid patients who are considering
      alternative therapies.

PMID- 16978950
TI  - Prospective randomized study comparing cryo-assisted and needle-wire localization
      of ultrasound-visible breast tumors.
AB  - BACKGROUND: This study compared the surgical results of 2 localization methods
      cryo-assisted localization (CAL) and needle-wire localization (NWL)-in patients
      undergoing breast lumpectomy for breast cancer. METHODS: A total of 310 patients
      were treated in an institutional review board-approved study with 18 surgeons at
      17 sites. Patients were randomized 2:1 to undergo either intraoperative CAL or
      NWL. A cryoprobe was inserted under ultrasound guidance in the operating room and
      an ice ball created an 8- to 10-mm margin around the lesion. The palpable ice
      ball then was dissected. NWL was placed according to institutional practice and
      resection was performed in a standard fashion. Surgical margins, complications,
      re-excisions, tissue volume, procedure times, ease of localization, specimen
      quality, and patient satisfaction were evaluated. Positive margins were defined
      as any type of disease present 1 mm or less from any specimen edge. RESULTS:
      Positive margin status did not differ between the 2 groups (28% vs. 31%). The
      volume of tissue removed was significantly less in the CAL group (49 vs. 66 mL, P
      = .002). Re-excisions were similar in both groups. CAL was superior in ease of
      lumpectomy, quality of specimen, acute surgical cosmesis, short-term cosmesis,
      patient satisfaction, and overall procedure time for the patient. CAL had a lower
      invasive positive margin rate (11% vs. 20%, P = .039) but a higher observed
      ductal carcinoma in situ-positive margin rate (30% vs. 18%, approaching
      statistical significance, P = .052). CONCLUSIONS: CAL is a preferred alternative
      to standard wire localization because it provides a palpable template, removes
      less tissue and improves cosmesis, decreases overall procedure time, and is more
      convenient for the patient and surgeon.

PMID- 16978952
TI  - Predictors of breast cancer development in a high-risk population.
AB  - BACKGROUND: The purpose of this study was to investigate the strongest predictors
      of breast cancer in a high-risk population and to increase our understanding of
      the possible interactions between risk factors. METHODS: The Women At Risk High
      Risk Registry provided the study population. The variables of interest included
      age at enrollment, presence of lobular carcinoma in situ (LCIS), atypical ductal
      hyperplasia (ADH), atypical lobular hyperplasia, family history of breast cancer,
      body mass index, and Gail scores (5-year high-risk > or =1.7%). Univariate and
      multivariate analyses were conducted with the Cox proportional hazards regression
      model and years of follow-up evaluation as the time scale. RESULTS: Out of 1553
      high-risk women, 79 (5%) developed breast cancer during a median follow-up period
      of 5 years. Results from the multivariate Cox model demonstrated that FHBC
      (hazard ratio [HR] = 1.76; 95% confidence interval [CI], 1.05-2.97), ADH (HR =
      1.90; 95% CI, 1.16-3.13), LCIS (HR = 1.71; 95% CI, .99-2.95), and a body mass
      index > or =30 (HR = 2.22; 95% CI, 1.14-4.35) were statistically significant
      predictors of breast cancer within this high-risk population. CONCLUSIONS: These
      results support current literature showing the synergistic increase in risk for
      patients with ADH, LCIS, and a positive family history of breast cancer. Obesity
      was also a strong predictor of breast cancer risk, which suggests that there may
      be a potentiating effect of obesity on other risk factors. Obesity may represent
      a modifiable risk factor, providing women with an opportunity to reduce their
      risk with lifestyle modification. Women with a strong family history of breast
      cancer or a diagnosis of ADH or LCIS may benefit most from risk-reduction
      strategies, chemoprevention, and surveillance.

PMID- 16978953
TI  - Less is more: transmammary axillary lymph node evaluation: an initial clinical
      experience.
AB  - BACKGROUND: Standard axillary node dissection has the potential to cause a
      significant amount of morbidity. Sentinel lymph node biopsy has considerably
      decreased this rate of morbidity; however, data recently presented, based on
      ACOSOG Z-10, suggest that even this less invasive technique can have a lymphedema
      rate as high as 7%. The transmammary axillary lymph node evaluation procedure
      (TANE) removes the sentinel node via the breast incision, thus eliminating the
      axillary incision. This may decrease morbidity, including lymphedema,
      dyesthesias, pain, and loss of range of motion, and it will also improve cosmetic
      outcome. METHODS: This is a prospective observational study to determine if it is
      feasible to perform both the partial mastectomy and sentinel lymph node biopsy
      via a single incision. All patients were consented for a partial mastectomy and
      sentinel lymph node biopsy. The partial mastectomy was performed in the standard
      fashion. The sentinel lymph node biopsy was performed via the same incision
      either before or after the breast specimen was removed. The sentinel lymph node
      biopsy was then performed in the standard fashion. RESULTS: The TANE method was
      attempted in 44 patients from June 2005 to March 2006 and was successful in 43,
      for a rate of 97.73%. The mean age of the patients was 57.6 years, with a range
      of 34 to 82 years. The average tumor size was 1.57 cm, with a range of 0.4 cm to
      4.5 cm. The TANE procedure was performed most often in patients with tumors
      located in the upper outer quadrant (79.54%). There were no perioperative
      complications. CONCLUSION: Our prospective study showed that this is a feasible
      procedure for sentinel lymph node biopsy and axillary lymph node dissection. The
      number of sentinel and axillary nodes obtained was within the standard published
      norms. Our technical success rate was 97.33%, and we did not have any
      perioperative complications. In this pilot study, there was the cosmetic benefit
      of only 1 incision. Future studies will examine if the TANE procedure can
      objectively decrease morbidity compared to a separate axillary incision.

PMID- 16978954
TI  - Paget's disease in the era of sentinel lymph node biopsy.
AB  - BACKGROUND: Paget's disease of the breast is an uncommon cancer. "Breast cancer"
      management has evolved to include sentinel lymph node biopsy (SLNB). Our
      objective is to determine utilization of SLNB in the surgical algorithm of
      Paget's disease. METHODS: After institutional review board approval, a database
      review of patients with Paget's disease was conducted. Patient demographics,
      tumor characteristics, treatment including use of SLNB, and survival were
      reviewed. Patient characteristics and outcomes were analyzed by using contingency
      table chi-square, pooled t tests, and log-rank tests for comparisons. RESULTS:
      Fifty-four patients with Paget's disease were identified and divided into 2
      cohorts (18 no SLNB and 36 SLNB). The mean age was 66 years for the no-SLNB group
      and 60 years for the SLNB group (P = .17). Paget's disease only was present in
      33%, Paget's disease + DCIS in 41%, and Paget's disease + invasive cancer in 26%.
      The mean invasive tumor size was 1.62 cm in the no-SLNB group and 1.59 cm in the
      SLNB group (P = .96). For invasive disease, ER/PR status was similar, but Her2
      was more likely to be overexpressed in SLNB (P = .04). Surgery choice ranged from
      "no surgery" to lumpectomy to mastectomy. Axillary staging was performed in 45 of
      54 patients, with 11% in both cohorts having nodal disease. A sentinel lymph node
      was identified in 97% of patients. Five-year overall and disease-free survival
      was 100% in the no-SLNB group and 88% in the SLNB group (P = .97) and 76% in the
      no-SLNB group and 84% in the SLNB group (P = .88), respectively. CONCLUSIONS:
      Paget's disease remains rare but should be treated similar to other "breast
      cancer." SLNB should be performed to evaluate the axilla when invasive disease is
      identified or a mastectomy is planned.

PMID- 16978955
TI  - The likelihood of additional nodal disease following a positive sentinel lymph
      node biopsy in breast cancer patients: validation of a nomogram.
AB  - BACKGROUND: Sentinel lymph node (SLN) biopsy examination is the current modality
      for evaluating the axilla in breast cancer patients. A nomogram has been
      developed to predict the likelihood of non-SLN metastases after a positive SLN
      biopsy examination. The purpose of this study was to validate the nomogram in a
      community breast center. METHODS: A prospective database was used to identify
      breast cancer patients with a positive SLN biopsy examination who underwent a
      completion axillary lymph node dissection. The nomogram was used to calculate the
      probability of having non-SLN involvement, and was compared with the observed
      numbers. RESULTS: The observed incidence of non-SLN involvement showed excellent
      correlation with the nomogram predicted probability (chi-square test statistic =
      5.87; P = .83). CONCLUSIONS: Predicting the risk of additional nodal metastases
      allows the surgeon and patient to make an individualized decision regarding the
      need for completion axillary lymph node dissection.

PMID- 16978956
TI  - Mammography as a screening tool for peripheral vascular disease.
AB  - BACKGROUND: Peripheral vascular disease (PVD) is a progressive and debilitating
      disease often diagnosed only when patients become symptomatic. Currently there
      are no widespread screening tests available for the early detection of PVD.
      Patients with diabetes and coronary artery disease are known to have a higher
      incidence of PVD. Prior studies have indicated that benign vascular
      calcifications seen on routine screening mammogram are more prevalent in women
      with diabetes and coronary artery disease. The same association has not been
      shown for women with PVD. The purpose of this study was to identify an
      association between benign vascular calcifications identified on mammography and
      PVD. If such an association exists then screening mammography, already widely
      used as a screening tool for breast cancer, may identify women at high risk for
      PVD. METHODS: To determine the incidence of vascular calcifications in our
      general screening population we prospectively evaluated consecutive routine
      screening mammograms for the presence of benign vascular calcifications. We then
      identified a population of women with PVD by using a computerized database
      maintained by the Division of Vascular Surgery. The population of women
      identified with PVD was categorized further to identify those women who had
      received routine screening mammogram within our hospital system. These mammograms
      were reviewed retrospectively with particular attention to the presence of
      vascular calcifications. All mammograms were reviewed by our dedicated
      mammographers. Statistical analysis of the study group using the chi-square test
      was performed to determine the association of PVD and mammographic vascular
      calcifications. RESULTS: Prospective evaluation of 645 women undergoing
      consecutive routine screening mammography identified 123 (19%) with benign
      vascular calcifications. By using our PVD computerized database between the years
      2002 and 2004 we identified 763 women with PVD. Of this group only 121 (15%) had
      undergone a routine screening mammogram in our hospital system. These mammograms
      were reviewed retrospectively by the same group evaluating the screening
      mammograms. On evaluation vascular calcifications were identified in 42% (51 of
      121) of these women with PVD. Statistical analysis was performed using the chi
      square test, odds ratio, and relative risk. A highly significant association was
      identified between PVD and the presence of mammographic vascular calcifications
      (P > .001). With a confidence interval of 95% the presence of benign vascular
      microcalcifications on routine screening mammogram identifies a significant risk
      for PVD with an odds ratio of 3.06. We showed through our analysis that women
      with calcifications are 2.19 times more likely to have PVD if microcalcifications
      are present. By using vascular calcifications identified on screening mammography
      as a means to identify women with PVD the sensitivity and specificity are 42% and
      80%, respectively. The positive predictive value and the negative predictive
      value are 29% and 88%, respectively, with an accuracy of 75%. CONCLUSIONS: This
      initial study indicates that the presence of vascular calcifications identified
      on routine screening mammogram is significantly higher in women with PVD and the
      lack of vascular calcifications on screening mammography correlates well with a
      negative history of PVD. We have identified a significant association with PVD
      and vascular calcifications in our patient population. Further studies are
      indicated to determine if screening mammography may become a widespread
      inexpensive screening tool to identify women at risk for PVD. Additional studies
      are underway at our institution to evaluate the association of PVD, diabetes and
      coronary artery disease, and vascular calcifications identified on routine
      screening mammography.

PMID- 16978957
TI  - Long-term outcomes of malignant phyllodes tumors patients: an institutional
      experience.
AB  - BACKGROUND: Malignant phyllodes tumors are an extremely rare breast tumor.
      Prognostic features and overall survival data have not been consistent across
      studies. METHODS: Retrospectively, we examined the clinicopathologic features of
      27 breast cancer patients treated for malignant phyllodes tumors from 1995 to
      2004 and analyzed their recurrence and survival outcomes using contingency
      tables, a logistic regression model, or a proportional hazard model. RESULTS: The
      mortality rate was 12% (n = 3) of the cohort and 75% of the group with distant
      metastases. The median follow-up period was 51 months (range, 12-192 mo). A
      mitotic index greater than 10 per high-powered field, the presence of stromal
      overgrowth, mastectomy at initial surgery, and larger tumor size were associated
      with an increased incidence of distant metastases. Larger tumor size also was
      associated with an increased incidence of death. CONCLUSIONS: Most patients with
      malignant phyllodes tumors will enjoy significant long-term survival if treated
      appropriately with local excision with clear margins.

PMID- 16978958
TI  - Side effects of aromatase inhibitors versus tamoxifen: the patients' perspective.
AB  - BACKGROUND: Hormonal therapy is a mainstay in the management of estrogen receptor
      positive (ER+) breast cancer. Tamoxifen (TAM) has been the drug widely used until
      the recent emergence of the aromatase inhibitors (AIs). Although AIs appear to be
      better tolerated than tamoxifen, they do have a different safety profile and
      these side effects have not been well characterized in community practice. We
      surveyed patients with ER+ breast cancers who received adjuvant hormonal therapy
      to determine how these medications impacted their quality of life and whether
      side effects or cost influenced decisions to continue therapy. METHODS: A mailed
      questionnaire and community cancer registry were used. RESULTS: Four hundred
      fifty-two of 902 surveys were returned for a 50% response rate. Eighty-two
      percent of respondents were placed on (adjuvant hormonal therapy) some form of
      estrogen-blocking therapy. Fifty-four percent of these were placed on tamoxifen
      and 46% on an AI. The most troublesome symptoms for tamoxifen and AI users,
      respectively, included hot flashes (35%/30%), weight gain (14%/15%), insomnia
      (17%/17%), and joint aches (12%/23%, P = .002). Thirty-nine percent of TAM users
      and 46% of AI users were taking medications to control their symptoms. Fifty
      percent of TAM users and 39% of AI users took vitamin E to help control hot
      flashes. Forty-two percent of TAM users versus 32% of AI users took Advil (Wyeth,
      Richmond, VA) for muscle/joint aches; 47.5% of AI users switched medication to
      improve symptoms as compared with only 37% of tamoxifen users (P = .015). The
      average cost of medications to control side effects for both tamoxifen and AI
      users was $67.36 per month. CONCLUSIONS: In our survey, both tamoxifen and AI
      users reported significant and different side effects. AI users suffered more
      frequently from musculoskeletal complaints, and more AI users switched therapy.
      Both AI and tamoxifen users used adjunctive medications for symptom control. In
      both groups, a large number used vitamin E to help hot flashes despite weak
      evidence to support its effectiveness in this setting. Cost of therapy and
      symptom control was not a major barrier to care.

PMID- 16978959
TI  - The significance of surgical margins for patients with atypical ductal
      hyperplasia.
AB  - BACKGROUND: The significance of surgical margins for patients with atypical
      ductal hyperplasia is unknown. PATIENTS AND METHODS: We reviewed our experience
      with atypical ductal hyperplasia and correlated the margin status of the
      specimens removed with the risk of recurrence as atypical ductal hyperplasia,
      ductal carcinoma in situ, and invasive carcinoma. Seven hundred forty-seven
      patients were identified between February 1995 and September 2005 as having
      biopsy proven atypical ductal hyperplasia (ADH). One hundred fifty-five of these
      patients were found to have "pure" atypical ductal hyperplasia without associated
      premalignant or malignant breast disease or a history of ipsilateral disease.
      Margin status of the initial excisional biopsy was noted and was correlated with
      the risk of recurrence. RESULTS: Of the 155 patients whose excisional biopsy
      specimens were "pure" atypical ductal hyperplasia, 44% (68) had negative margins,
      5% (7) had positive margins, and 52% (80) were not reported. No patient underwent
      re-excision for close or positive margins. Follow-up ranged from 0 to 119 months,
      with a mean of 26 months. Seven patients (5%) presented with new findings at the
      site of their initial excisional biopsy, 1 of whom was found to have an invasive
      ductal carcinoma and 6 of whom had benign findings. Of the 87 patients with
      margins positive or unknown for ADH at surgical excision, none went on to develop
      malignancy. CONCLUSION: Our results suggest that clear surgical margins at
      surgical excision for atypical ductal hyperplasia did not affect the risk of
      subsequently developing a malignancy.

PMID- 16978960
TI  - Intramammary lymph nodes and breast cancer: a marker for disease severity, or
      just another lymph node?
AB  - BACKGROUND: Axillary lymph node status is still considered the most significant
      prognostic factor for breast cancer outcome, and treatment decisions are based on
      the presence or absence of nodal disease. Intramammary lymph nodes (IMLNs) can be
      a site of regional spread. Is this a marker for more aggressive disease? METHODS:
      We reviewed the cancer center pathology database from 1991 to 2005 for all cases
      of breast cancer with IMLNs. RESULTS: IMLNs were identified in 64 breast cancer
      patients, with metastatic spread in 20 patients, and benign IMLNs described in 44
      patients. Positive IMLNs were associated with more aggressive disease, including
      higher rates of invasive versus noninvasive cancers (5% ductal carcinoma-in-situ
      [DCIS] with positive IMLNs vs. 23% with negative IMLNs), lymphovascular invasion
      (55% vs. 11%), and a higher rate of axillary lymph node involvement (72% vs.
      18%). Patients with positive IMLNs were also more likely to undergo mastectomy
      (75% vs. 54%). CONCLUSIONS: IMLN metastases are a marker for disease severity;
      recognition of this may influence choice of adjuvant therapy. The presence of
      metastatic disease in an IMLN is associated with a high rate of axillary nodal
      involvement, and should mandate axillary dissection. Preoperative
      lymphoscintigraphy may help identify these extra-axillary metastases.

PMID- 16978961
TI  - The relationships among clinician delay of diagnosis of breast cancer and tumor
      size, nodal status, and stage.
AB  - BACKGROUND: The objective of this study was to determine the impact of delay of
      diagnosis by clinicians on breast cancer prognostic factors and survival.
      METHODS: The medical records of patients whose breast cancer diagnosis was
      delayed by clinicians were reviewed. Data collected included primary tumor
      diameter, number of positive lymph nodes, tumor grade, pathologic stage, length
      of diagnostic delay, and follow-up status. Data were analyzed for correlations
      between prognostic factors and length of delay. The Fisher exact test was used to
      correlate delay and stage with survival. RESULTS: Forty patients had delays from
      3 to 36 months. There were no significant correlations between delay and natural
      log of primary tumor diameter (r = -.16, P = .33), number of positive lymph nodes
      (r = .22, P = .90), tumor grade (R = -.16, P = .36), or pathologic stage (R = 
      .09, P = .59). A higher stage correlated with decreased survival (P = .03), but
      delay did not. CONCLUSIONS: Clinician diagnostic delays of up to 36 months did
      not correlate with worsening prognostic factors or with survival rates.

PMID- 16978963
TI  - Intraoperative digital specimen mammography: prompt image review speeds surgery.
AB  - Specimen mammograms are often a time-consuming event for image-guided surgery.
      The use of an intraoperative imaging device may improve the speed of surgery, but
      comparison must be made to ensure accuracy is maintained. One hundred fifty
      consecutive image localized patients underwent both intraoperative digital
      specimen mammogram (in the operating room) and standard specimen mammogram (in
      radiology). Intraoperative mammograms as read by breast surgeons were as accurate
      as standard films while saving an average of 19 minutes per operative procedure.
      Intraoperative digital specimen mammograms can accurately identify target lesions
      while saving operating room time.

PMID- 16978962
TI  - The influence of additional surgical margins on the total specimen volume excised
      and the reoperative rate after breast-conserving surgery.
AB  - BACKGROUND: It is unclear whether the additional removal of breast tissue during
      breast-conserving therapy (BCT) for breast cancer beyond the standard lumpectomy
      reduces the incidence of inadequate microscopic margins found at pathological
      examination and subsequent reoperation. This study compares the reoperative rates
      after initial BCT in 3 groups of patients who underwent lumpectomy with complete
      resection of 4 to 6 additional margins, lumpectomy with selective resection of 1
      to 3 additional margins, or standard lumpectomy. METHODS: Retrospective data were
      reviewed from 171 selected cases of BCT, from May 2000 to February 2006. Forty
      five cases involved lumpectomy with complete resection of 4 to 6 additional
      margins; 77 involved lumpectomy with selective resection of 1 to 3 additional
      margins, whereas 49 involved standard lumpectomy. All samples underwent
      pathologic analysis of inked resection margins by permanent section. The 3 groups
      were compared for patient demographics, tumor size and histologic subtype, tumor
      stage, margin status, excised specimen volume, and eventual subsequent
      reoperation. Adequate surgical margin was defined as any negative margin greater
      than 2 mm. RESULTS: The group with complete resection of 4 to 6 additional
      margins had a subsequent reoperation rate of 17.7%, whereas the group with
      selective resection of 1 to 3 additional margins and the standard lumpectomy
      group had a subsequent reoperation rate of 32.5% and 38.7%, respectively, because
      of inadequate margins. The mean total excised specimen volume in the 3 groups was
      129.19, 46.04, and 37.44 cm3, respectively. CONCLUSIONS: The complete resection
      of 4 to 6 additional margins during the initial BCT resulted in the lowest
      subsequent reoperation rate, and the largest total volume specimen excised among
      the 3 techniques studied.

PMID- 16978964
TI  - Accuracy of intraoperative imprint cytology of sentinel lymph nodes in breast
      cancer.
AB  - BACKGROUND: In breast cancer treatment, immediate completion of axillary lymph
      node dissection (ALND) can be performed if the intraoperative sentinel lymph node
      (SLN) examination is positive. This study evaluates the accuracy of
      intraoperative imprint cytology (IC) for detecting SLN metastases. METHODS:
      Pathology reports from 385 SLN biopsy examinations were reviewed retrospectively.
      The SLNs were serially sectioned perpendicular to the long axis and IC was
      performed intraoperatively. The SLNs then were formalin-fixed for permanent
      sections. Final pathology was compared with the intraoperative IC results.
      RESULTS: The sensitivities for IC detection of N0(i+) (n = 36), N1mi (n = 24),
      and N1a-3a (n = 65) metastases were 0%, 4%, and 74%, respectively. The
      specificity was 100%. CONCLUSIONS: Final pathology identified 89 (23%) patients
      with N1 or greater disease. IC allowed 49 (55%) of these patients to undergo
      synchronous completion of ALND. No unnecessary completion ALNDs were performed.
      The sensitivity of IC decreased with decreasing size of the metastasis.

PMID- 16978966
TI  - A breast center review of compliance with National Comprehensive Cancer Network
      Breast Cancer guidelines.
AB  - BACKGROUND: National Comprehensive Cancer Network (NCCN) guideline compliance for
      breast cancer was determined in a breast center. METHODS: A retrospective study
      of 200 new breast cancer patients seen in 2004 was performed. RESULTS: NCCN
      guideline compliance rates for preoperative evaluation, breast surgery, lymph
      node surgery, radiation treatment, and systemic adjuvant therapy were 87%, 97%,
      97%, 77%, and 63%, respectively. The most common reasons for noncompliance were
      partial breast radiation, no radiation, limited life expectancy, and patient
      choice to defer systemic treatment. CONCLUSIONS: The investigation of quality of
      breast cancer care requires measurement of compliance and reasons for
      noncompliance with established guidelines. A review that focuses only on
      percentage compliance has the potential to penalize institutions that (1)
      practice informed consent detailing absolute risks of survival with and without
      systemic therapy, (2) practice evidence-based medicine before the standardized
      guideline is changed to reflect it, and (3) serve populations with limited life
      expectancy.

PMID- 16978965
TI  - Biologic significance of false-positive magnetic resonance imaging enhancement in
      the setting of ductal carcinoma in situ.
AB  - BACKGROUND: Imaging patterns of benign proliferative processes often complicate
      the assessment of ductal carcinoma in situ (DCIS) by magnetic resonance imaging
      (MRI). We investigated the pathologic and biologic characteristics of false
      positive enhancement by breast MRI. METHODS: DCIS (n = 45), benign (n = 5), and
      false-positive (MRI enhancement and nonmalignant pathology) (n = 10) cases were
      characterized by immunohistochemistry and MRI features. RESULTS: For DCIS cases,
      images that overestimated pathologic size had heterogeneous enhancement on MR,
      were estrogen receptor positive, and were low grade by pathology. False-positives
      had higher rates of proliferation, angiogenesis, and inflammation compared with
      benign tissue but lower values than DCIS. Benign proliferative processes
      accounted for all false-positive and size overestimated cases. CONCLUSIONS:
      Lesions that enhance on MRI have higher proliferation, angiogenesis, and
      inflammation compared with nonproliferative breast tissue. Benign proliferative
      processes often enhance on MRI and are difficult to differentiate from low-grade,
      ER+ DCIS lesions. False-positive MRI enhancement may reflect a spectrum of change
      within high-risk tissue.

PMID- 16978967
TI  - Surgical management of recurrent subareolar breast abscesses: Mayo Clinic
      experience.
AB  - BACKGROUND: Recurrent subareolar abscess is an uncommon condition of the breast.
      The disease process often is managed inadequately by repeated courses of
      antibiotics and/or incision and drainage procedures that temporarily may relieve
      the abscess collection but fails to correct the primary inciting process.
      Repeated surgical procedures may lead to multiple scars, nipple and breast
      distortion without cure of the problem, or even to mastectomy. METHODS: We report
      a retrospective review of patients who have been treated surgically with this
      condition at a single institution from 1993 to 2005. RESULTS: Successful
      definitive treatment of retroareolar abscesses necessitates excision of the
      central nipple, including the obstructed ducts. CONCLUSIONS: This technique
      achieves a cure rate of 91% and an overall 95% satisfaction rate in the cosmetic
      outcome of the nipple.

PMID- 16978968
TI  - Identification of breast cancer in patients with pathologic nipple discharge:
      does ductoscopy predict malignancy?
AB  - OBJECTIVE: The purpose of the current study was to review characteristics of
      patients with nipple discharge who underwent ductoscopy-assisted excisional
      biopsy who had a final diagnosis of carcinoma. METHODS: A retrospective review
      was performed of patients presenting with pathologic nipple discharge (PND) who
      underwent ductoscopy-assisted excisional biopsy and had a final diagnosis of
      carcinoma. RESULTS: A total of 14 (7%) of 188 patients who underwent ductoscopy
      assisted excision had a final pathology of ductal carcinoma-in-situ (DCIS)
      (12/14, 86%) or invasive breast cancer with DCIS (2/14, 14%). Duct wall
      irregularities or intraluminal growths were visualized during ductoscopy in 8 of
      the 14 (57%) breast cancer patients. There were no visual abnormalities noted
      during ductoscopy that accurately predicted a final diagnosis of malignancy.
      CONCLUSIONS: Although occult malignancies can be identified in patients
      undergoing ductoscopy-assisted biopsy for PND, no clear morphologic changes
      visualized during ductoscopy definitively indicated the presence of malignancy.

PMID- 16978969
TI  - Correlation between core biopsy and excisional biopsy in breast high-risk
      lesions.
AB  - BACKGROUND: The purpose of the current study was to compare the prevalence of
      invasive or in situ cancer at excisional biopsy in patients with image-guided
      core needle biopsy (CNB)-proven atypical ductal hyperplasia (ADH), atypical
      lobular hyperplasia (ALH), or lobular carcinoma-in-situ (LCIS). Factors affecting
      the upgrade rate to malignancy were also identified. METHODS: Patients diagnosed
      with ADH, ALH, or LCIS on image-guided CNB (stereotactic or ultrasound) from 1995
      to 2005 were identified through radiologic and surgical databases. Patients who
      subsequently underwent excisional biopsy of their lesion were included in the
      study. The imaging, medical records, and pathology of these patients were
      reviewed. RESULTS: Ninety-six patients with either ADH (61/96, 63%), ALH (19/96,
      20%), or LCIS (16/96, 17%) on image-guided CNB proceeded to excisional biopsy.
      Malignancy was detected on excisional biopsy in 31% of patients with ADH, 16% of
      patients with ALH, and 25% of patients with LCIS. There were no significant
      differences between the 2 groups in terms of age, parity, hormonal status, or
      previous benign breast biopsies. The presence of a mass on mammography was
      associated with an increased upgrade rate to malignancy, while biopsies performed
      using vacuum-assisted devices, larger gauge biopsy needles, and greater number of
      cores were associated with a lower upgrade rate. CONCLUSIONS: Our data suggest
      that excisional biopsy is warranted in all patients with CNB diagnoses of ADH,
      ALH, or LCIS to exclude the presence of cancer.

PMID- 16978970
TI  - Influence of breast cancer margin assessment method on the rates of positive
      margins and residual carcinoma.
AB  - BACKGROUND: We hypothesized that the method of breast cancer margin assessment
      may be associated with different rates of positive margins and residual
      carcinoma. METHODS: A total of 178 breast cancer specimens were divided into 2
      groups (A and B) based on the margin assessment method used. Rates of positive
      margins, re-excision, and residual carcinoma at re-excision were compared and
      analyzed statistically. RESULTS: At least 1 margin was positive in 64.7% in group
      A and in 65.2% in group B. At directed re-excision 54% in group A and 51% in
      group B had residual carcinoma. The lateral margin was positive in 44% in group A
      compared with 26% in group B (P = .06). The posterior margin was positive in 19%
      in group A and in 51% in group B (P = .001). CONCLUSIONS: Two different breast
      cancer specimen margin assessment methods had comparable rates of positive
      margins and residual carcinoma at re-excision. Different patterns of specific
      margin positivity suggest that the method of margin assessment may alter results.

PMID- 16978971
TI  - Breast cancer in the very elderly: treatment patterns and complications in a
      tertiary cancer center.
AB  - BACKGROUND: The risk of developing breast cancer rises with increasing age. The
      very elderly population (80 years of age and greater) is often excluded from both
      clinical trials and retrospective analyses. We performed a retrospective review
      of the very elderly population treated at our institution in order to assess
      treatment patterns and the safety of therapy in an older population. DATA
      SOURCES: In this institutional experience at a comprehensive cancer center, we
      retrospectively reviewed the charts of patients 80 years and older diagnosed with
      a new breast cancer between September 1, 1989, and September 1, 2004. RESULTS:
      Two hundred thirteen patients were identified for this study. Median age was 83
      (range 80-97). Median survival was 7.28 years, with a median follow up of 4 years
      for patients still alive at the end of the study period. Ninety-eight percent of
      patients (208/213) received 1 or more components of recommended multimodality
      treatment. Five patients refused all treatment. Overall, complications affected
      12% of patients who received treatment (26/208). There were 2 deaths, 1 after
      surgery and 1 related to chemotherapy. The majority, 69% (18/26), of the
      documented complications were classified as minor. Surgery resulted in
      complications in 6% (11/188) of patients. Five percent (5/112) of patients who
      received radiation suffered adverse effects. Chemotherapy-related complications
      affected 30% (6/18) of treated patients. Hormonal agents resulted in
      complications in 3% (3/112) of patients. No correlation between the American
      Society of Anesthesiologists score and incidence of complication was observed (P
      = .58). CONCLUSIONS: Very elderly patients can be safely treated with surgery and
      radiation in accordance with accepted recommendations for their stage of breast
      cancer. Treatment with surgery and/or radiation should be considered despite age
      and moderate comorbidity in order to affect locoregional control. Chemotherapy
      results in a significant incidence of complications and should be cautiously
      implemented in this age group. A prospective trial is necessary to assess the
      necessity of aggressive multimodality therapy in this very elderly population.

PMID- 16978972
TI  - Percutaneous radiofrequency-assisted excision of fibroadenomas.
AB  - INTRODUCTION: Fibroadenomas are a frequently encountered benign tumor that will
      occur in approximately 10% of women during their lifetime. Although the natural
      history would suggest fibroadenomas diagnosed with minimally invasive needle core
      biopsy can be safely observed, the majority are still surgically removed in the
      operating room. In an effort to limit the more than 500,000 surgical fibroadenoma
      removals performed each year, percutaneous excision has become a viable
      alternative. Percutaneous excision of intact fibroadenomas versus removal with a
      multiple core sampling technique has the dual potential advantage of causing
      minimal intervention combined with provision of adequate sample for thorough
      histopathology and margin analysis for confirmation of complete removal. An 18
      month retrospective analysis was undertaken to evaluate the utilization of a new
      radiofrequency-assisted biopsy device in the successful removal and continued
      absence of histologically confirmed fibroadenomas on 4- to 6-month follow-up
      imaging. METHODS: Between April 2004 and November 2005, 100 patients underwent
      ultrasound- or stereotactic-guided, radiofrequency-assisted intact percutaneous
      excision of 106 diagnosed fibroadenomas of the breast. Patients were comprised of
      100 women whose ages ranged from 18-70 years (median age, 45 years). RESULTS:
      Indications for the procedure included palpable mass, 77; abnormal mammogram, 13;
      and abnormal ultrasound, 10, as the patient's initial presentation. Ultrasound
      was used to guide the procedure in 82 patients, and stereotactic was used in 18
      patients. One early study procedure was performed under general anesthesia; the
      remaining studies were performed under local anesthesia (1% lidocaine) using from
      10 to 45 mL. On pathologic examination, the tumors ranged in size from 6 to 27 mm
      (mean diameter, 14 mm) and weighed from 0.6 to 2.0 g (mean weight, 1.0 g).
      Patients reported minimum discomfort related to the procedure; pain scores ranged
      from 0 to 10 (mean pain score, <1). Complications were minimal, with only 2
      patients having bleeding, which was controlled by conservative measures. At the 4
      to 6-month follow-up, 79 of 85 (93%) evaluable patients showed no physical or
      imaging evidence of residual fibroadenoma, an additional 5 patients have reported
      no physical findings or further complaints and have required no further need for
      medical evaluation, 8 have been lost to follow-up, and 2 have yet to be
      reevaluated. CONCLUSIONS: Percutaneous ultrasound- or stereotactic-guided,
      radiofrequency-assisted excision of fibroadenomas of the breast may be performed
      in an ambulatory setting under local anesthesia. The procedure provides intact
      specimens that in most cases appear to be completely removed after follow-up of 4
      to 6 months. The procedure is well tolerated by patients and is associated with
      minimal complications.

PMID- 16978973
TI  - Virtual 3-dimensional modeling as a valuable adjunct to aesthetic and
      reconstructive breast surgery.
AB  - Three-dimensional (3D) imaging technology currently is used by various commercial
      industries as a method for analyzing objects and shapes. Recent work from our
      group and others offer data to support the use of 3D imaging as a valuable tool
      in aesthetic and reconstructive breast surgery. We have developed a system for
      creating 3D breast models that provides clinical data that can help guide
      surgical management. With 3D breast models, surgeons are able to visually assess
      the size, shape, contour, and symmetry of the breast, as well as obtain
      quantitative breast measurements and volumetric calculations. Three-dimensional
      imaging may be applied to various plastic surgery procedures including breast
      reconstruction with implant/tissue expanders, local flap reconstruction, free
      flap reconstruction, breast augmentation, and breast reduction surgery. The novel
      application of 3D imaging in these settings represents a significant advance from
      traditional approaches to aesthetic and reconstructive breast surgery in which
      surgical procedures are based on 2-dimensional photographs and visual size
      estimates.

PMID- 16978974
TI  - Outcomes of breast-conservation therapy for invasive lobular carcinoma are
      equivalent to those for invasive ductal carcinoma.
AB  - BACKGROUND: Breast-conservation therapy (BCT), including wide local excision and
      postoperative irradiation, is considered standard treatment for early-stage
      invasive ductal carcinoma (IDC). The use of BCT in patients with invasive lobular
      carcinoma (ILC) has been questioned because of concerns regarding ipsilateral
      breast recurrence and risk of bilateral breast cancer. We evaluated our
      institutional experience with BCT and compared treatment outcomes for ILC with
      those for IDC. METHODS: A review of our BCT database revealed 84 patients with
      ILC and 1,126 with IDC with stage I or II disease treated with BCT and radiation
      between 1976 and 1999. We evaluated local-regional recurrence, disease-specific
      survival, and contralateral breast cancer rates in both groups. RESULTS: The 5-
      and 10-year local-regional recurrence rates for the ILC group were 1% and 7%,
      respectively, and 4% and 9%, respectively, for the IDC group (P = .70). There
      were no significant differences in the 5- and 10-year disease-specific survival
      rates between the groups. Contralateral breast cancer occurred in 11.3% of
      patients with IDC and 11.9% of patients with ILC. CONCLUSIONS: BCT achieves
      similar local-regional control and survival outcomes in selected patients with
      ILC or IDC. Breast-conservation therapy is an appropriate treatment strategy for
      patients with early-stage invasive lobular carcinoma.

PMID- 16978975
TI  - Laparoscopically harvested omental flap for immediate breast reconstruction.
AB  - BACKGROUND: Breast cancer surgery and accompanying breast reconstruction have
      been diversified. We report our experience of immediate breast reconstruction
      using laparoscopically harvested omental flap (LHOF). METHODS: During a 44-month
      period, 44 immediate breast reconstructions with LHOF were performed. Patients
      were followed up for complications and cosmetic results. RESULTS: Forty cases of
      pedicled LHOF and 4 cases of free LHOF were performed after either nipple-sparing
      mastectomy (n = 21) or breast-conservation treatment (n = 23). Morbidity included
      1 minor vascular injury (2.3%) of the LHOF, 4 wound and graft infections (9.1%),
      and 1 epigastric hernia (2.3%). Cosmetic results were mostly satisfactory, with a
      soft breast that was natural in appearance. Donor-site scars were minimal.
      However, in 5 patients (12.5%), omental flap size was found to be inadequate
      during the procedure. CONCLUSIONS: Although there is a limit of volume, LHOF is
      an attractive autologous flap, which makes a natural soft breast and minimal
      deformity of the donor site.

PMID- 16978976
TI  - Normal anatomy and common labral lesions at MR arthrography of the shoulder.
AB  - MR arthrography of the shoulder is the most accurate imaging modality in
      demonstrating abnormalities of the glenoid labrum and associated structures.
      Tears of the labrum, the capsule or the gleno-humeral ligaments can lead to pain,
      catching, popping or instability. The anatomy of this region is complex. We
      present the normal anatomy of the glenoid labrum, biceps anchor and gleno-humeral
      ligaments together with their normal variants and then describe common labral
      ligamentous pathologies.

PMID- 16978977
TI  - MR staging of endometrial carcinoma.
AB  - Endometrial cancer is the second most common gynaecological malignancy. The usual
      presentation with post-menopausal bleeding results in an early diagnosis in most
      cases and thus there is opportunity for cure. Magnetic resonance (MR) imaging is
      pivotal in the decision-making process regarding treatment options. We present a
      review of the magnetic resonance (MR) findings to illustrate its role in the
      staging of endometrial cancer.

PMID- 16978978
TI  - The radiology of IRIS (immune reconstitution inflammatory syndrome) in patients
      with mycobacterial tuberculosis and HIV co-infection: Appearances in 11 patients.
AB  - AIM: To determine the radiological manifestations of IRIS (immune reconstitution
      inflammatory syndrome) in patients with HIV and mycobacterium tuberculosis co
      infection, in the context of their demographic and clinical data. MATERIALS AND
      METHODS: The radiological imaging, demographic and clinical data of 11 patients
      diagnosed with IRIS associated with HIV and mycobacterial tuberculosis co
      infection were studied retrospectively. Where available, follow-up imaging
      studies were also reviewed. RESULTS: The most common radiological feature of IRIS
      was lymph node enlargement (73%), with central low attenuation centres, in
      keeping with necrosis, present in most of these cases (88%). Most commonly
      affected were intra-abdominal nodes (70%), followed by axillary (40%) and
      mediastinal lymph nodes (36%). Within the lung parenchyma, diffuse, bilateral
      pulmonary nodules were seen in 55% of cases. Unilateral small volume pleural
      effusions were seen in two cases with associated parenchymal changes seen in only
      one. Small volume ascites was seen in two cases. Thirty-six percent of cases
      presented with new or worsening abscesses despite treatment. In this context,
      image-guided radiological drainage proved a useful adjunct to the conventional
      medical therapy for IRIS. The most common clinical signs of IRIS included fever
      (64%), abdominal pain (36%) and cough (27%). CONCLUSION: We have described the
      radiological features that are characteristic in IRIS and the importance of
      putting these into context with the clinical and pathological findings as part of
      a multidisciplinary approach in making the diagnosis. The role of the radiologist
      is central in diagnosis, monitoring of disease progression and management of
      complications in patients with IRIS.

PMID- 16978979
TI  - In utero magnetic resonance of non-isolated ventriculomegaly: Does ventricular
      size or morphology reflect pathology?
AB  - AIM: To confirm whether ventricular size or morphology reflects the underlying
      pathology in foetuses referred with a diagnosis of possible ventriculomegaly (Vm)
      and central nervous system (CNS) pathology. METHODS: Retrospective analysis of 40
      in utero magnetic resonance (MR) examinations was undertaken. Ventricular size
      was measured on axial sections by two observers, and morphology was agreed by
      consensus. Results were analysed according to gestational age at referral, degree
      of Vm (mild 10-15 mm, moderate/severe >15 mm) and morphology. RESULTS: Nine cases
      had no Vm (mean gestational age 23.6 weeks, range 19-33), 17 had mild Vm (mean
      age 23.9 weeks, range 20-31), and 14 had moderate/severe Vm (mean age 25.9 weeks,
      range 20-35). All groups had a mix of morphology and pathology. Eighteen
      suspected cases of spina bifida were referred and 17 confirmed (mean age 22.6
      weeks, range 19-30) using MR. The morphology was mixed, five cases (27.8%) had an
      angular appearance (this morphology was only seen in cases with spina bifida).
      Fourteen cases (77.8%) had Vm (eight mild, six severe). Of the thirteen cases of
      agenesis of the corpus callosum (ACC) suspected on ultrasound, seven were
      confirmed using MR (mean age 26.5 weeks, range 20-35). Of those seven cases with
      ACC confirmed on MR, and three additional cases only detected by in utero MR,
      five had colpocephaly, seven had Vm (four mild, three severe). CONCLUSION:
      Severity of Vm did not reflect the type, or presence, of underlying pathology.
      Morphology appears an indicator of pathology. Angular ventricles should initiate
      a search for spinal defects. Colpocephaly may indicate ACC.

PMID- 16978980
TI  - A survey of follow-up practice of urologists across Britain and Ireland following
      nephrectomy for renal cell carcinoma.
AB  - AIM: To determine the follow-up protocol for interval assessment of patients
      following radical nephrectomy for renal cell cancer and to compare them with the
      recommendations proposed in the literature. METHODS: Consultant urologists across
      Britain and Ireland completed a postal questionnaire. One follow-up mailing was
      used to encourage non-responders. The responses were analysed in the light of the
      recommendations from European Association of Urology and American guidelines.
      Also information was collected from the respondents on the choice of follow-up
      investigations for renal cell cancer and the total duration of follow-up.
      RESULTS: Of the 480 urologists surveyed 292 (60.8%) responded. Most respondents
      recommended regular follow-up with chest radiography (CR), ultrasound and
      computed tomography (CT). For T1 disease CR was requested by 28, 62 and 55%; for
      T2 disease by 30, 66 and 51%; for T3 disease by 39, 63, and 48% at 3, 6 and 12
      months, respectively. For T1 disease US was requested by 5, 23 and 30%; for T2
      disease 6, 27 and 30%; for T3 disease 8, 25, and 26% at 3, 6 and 12 months,
      respectively. For T1 disease an abdominal CT was requested by 2, 17 and 21%; for
      T2 disease 3.7, 19.5 and 26%; for T3 disease 10, 31, and 33% at 3, 6 and 12
      months, respectively. Only one respondent followed the guidelines suggested in
      the literature. Further follow-up after 12 months for 5 and 10 years was
      suggested by 58.2 and 21.3% for T1, 53 and 24.73% for T2, and 45.5 and 25.5% for
      T3, respectively. There is appreciable variation in the frequency of use and
      timing of imaging. CONCLUSIONS: Most respondents perform follow-up after radical
      nephrectomy in patients with renal cancer, with considerable variability in their
      practices. In the current increasingly cost-conscious healthcare industry a
      scientifically justified follow-up should be considered.

PMID- 16978982
TI  - Radiology findings in adult patients with vocal fold paralysis.
AB  - AIM: To compile imaging findings in patients with vocal fold paralysis. MATERIALS
      AND METHODS: A retrospective analysis of the medical charts of 100 consecutive
      patients, admitted to our department with vocal fold paralysis was undertaken.
      After laryngoscopy, patients were referred for radiological work-up depending on
      their clinical history and clinical findings. Ultrasound of the neck and/or
      contrast-enhanced spiral computed tomography (CT) of the neck and mediastinum was
      performed, extending to include the whole chest if necessary. In one patient, CT
      of the brain and in two patients, magnetic resonance angiography was undertaken.
      Analysis of the clinical and radiological data was performed to assess the most
      frequent causes for vocal fold paralysis. RESULTS: In 66% of patients, the
      paralysis was related to previous surgery. Thirty-four percent of cases were
      labelled idiopathic after clinical examination. After imaging and follow-up, only
      8% remained unexplained. Nine patients suffered from neoplasms, four from
      vascular disease, and 12 from infections. One patient developed encephalomyelitis
      disseminata on follow-up. CONCLUSION: Thorough radiological work-up helps to
      reduce the amount of idiopathic cases of vocal fold paralysis and guides
      appropriate therapy.

PMID- 16978983
TI  - Paediatric 99mTc-DMSA imaging: Reducing distress and rate of sedation using a
      psychological approach.
AB  - AIM: To evaluate the effect of a psychological approach on distress and sedation
      rates in children undergoing dimer captosuccinic acid-labelled with technetium-99
      (99mTc) DMSA imaging. MATERIALS AND METHODS: Baseline data, on a retrospective
      consecutive sample of children examined using DMSA over a 6-month period (n =
      81), were collected via medical note search and postal questionnaire. A further
      consecutive sample of 40 children was recruited prospectively to the
      intervention, which consisted of distraction during medical procedures and
      environmental manipulation. In addition half of the intervention group were
      provided with a photo-booklet depicting a coping child model, together with a
      letter offering advice to parents on how to prepare their child for the
      procedure. RESULTS: Sedation rates were lower (p = 0.003) and service
      satisfaction ratings higher (p = 0.002) in the Intervention group as compared
      with the Baseline group. Within the intervention condition, children who received
      the photo-booklet displayed less distress before the procedure (p = 0.01) than
      those who did not. Also families who received the photo-booklet were more likely
      to attend the appointment (p = 0.024). CONCLUSION: In this study, the use of a
      psychological approach was associated with lower rates of distress and sedation
      in children undergoing 99mTc-DMSA imaging, without compromising image quality.

PMID- 16978984
TI  - Benign localized fibrous tumour of the pleura: CT features with histopathological
      correlations.
AB  - AIM: To assess the CT features of benign localized fibrous tumour of the pleura,
      with histopathological correlations. MATERIALS AND METHODS: CT and
      histopathological findings of 18 patients with surgically resected benign
      localized fibrous tumour of the pleura were retrospectively assessed. RESULTS:
      Tumours were pleura or fissure based, semilunar, lentiform or oval in shape,
      classified according to their homogeneous, slightly heterogeneous or
      heterogeneous enhancement pattern. Of the 18 tumours, 5 (28%) demonstrated > or =
      55 HU increment or higher attenuation than muscles on contrast-enhanced CT, and
      histopathologically showed a haemangiopericytoma-like pattern with rich
      vascularity. CONCLUSION: CT analysis of the shape of a mass and the enhancement
      pattern can be helpful in the diagnosis of benign localized fibrous tumour of the
      pleura.

PMID- 16978985
TI  - Air trapping on computed tomography images of healthy individuals: effects of
      respiration and body mass index.
AB  - AIM: To evaluate the relationships of changes in the lung area during respiration
      and of individual body mass index (BMI) to air trapping on expiratory computed
      tomography (CT) in young non-smoking adults of either gender. METHODS: The
      volunteers were 10 women and 10 men (mean age 25.7 years) who were healthy
      lifelong non-smokers. We obtained both end-inspiratory and end-expiratory CT
      images at three levels: the upper, middle and lower lung. The ratio of cross
      sectional lung area upon expiration to cross-sectional lung area upon inspiration
      (lung area ratio) was determined for each lung at each of the three levels. In
      cases showing air trapping, we calculated the percentage of area of air in
      relation to the total lung area in each section. BMI was calculated for each
      participant. RESULTS: Air trapping was present in dependent areas of the lungs of
      6 women and 5 men. The mean percentage of area of air trapped was statistically
      greater for men (9.8+/-9.2%) than for women (4.9+/-5.2%). The mean lung area
      ratio was 0.52+/-0 14 among volunteers with air trapping (66 sections) and 0.69+/
      0.12 among those without air trapping (54 sections) (p < 0.001). At each lung
      level, the mean lung area ratio was greater in individuals with air trapping than
      in those without. Mean BMI was also greater in these people (p = 0.009).
      CONCLUSION: Change in the respiratory lung area and BMI contribute to development
      of air trapping.

PMID- 16978986
TI  - Technical report: Lipiodol-guided computed tomography for radiofrequency ablation
      of hepatocellular carcinoma.

PMID- 16978987
TI  - Case report: Multicentric carpal/tarsal osteolysis: imaging review and 25-year
      follow-up.

PMID- 16978988
TI  - Case report: Renal extramedullary haematopoiesis mimicking renal lymphoma on
      computed tomography.

PMID- 16978989
TI  - Case report: Perforated haemorrhagic cholecystitis: MR imaging features.

PMID- 16978990
TI  - Ultrasound diagnosis of clinically undetected Clostridium difficile toxin
      colitis.

PMID- 16978991
TI  - Mammotome biopsy: Impact on preoperative diagnosis rate.

PMID- 16978992
TI  - Erectile dysfunction in heart failure patients.
AB  - Chronic heart failure (HF) and erectile dysfunction (ED) are 2 highly prevalent
      disorders that frequently occur concomitantly. Coronary artery disease, HF, and
      ED share several common risk factors, including diabetes mellitus, hypertension,
      smoking, and dyslipidemia. Additionally, the distinct physiologic sequelae of HF
      create unique organic and psychologic factors contributing to ED in this patient
      population. Standard HF therapy with beta-receptor blockers, digoxin and thiazide
      diuretics may worsen sexual dysfunction owing to medication side effects. This
      may, in turn, lead to noncompliance in misguided efforts to retain satisfactory
      sexual activity, with secondary worsening of cardiac capacity. This review
      describes the unique aspects of ED in the HF population.

PMID- 16978993
TI  - Facilitated percutaneous coronary intervention.
AB  - The goal of the initial treatment for ST-segment elevation myocardial infarction
      is rapid and effective reperfusion. Randomized trials have demonstrated that
      primary angioplasty is preferred over thrombolysis if done in a timely manner and
      by an experienced team. However, due to many factors, performance of primary
      angioplasty within the goal of 90 min is often not possible. A combined strategy
      of immediate thrombolysis in the emergency room or in the ambulance followed by
      angioplasty theoretically could provide early reperfusion with subsequent
      angioplasty to insure complete reperfusion. Over 17 clinical trials have been
      reported. Compared with thrombolysis, facilitated angioplasty in the most recent
      trials has been shown to have a more favorable long-term outcome. Trials
      comparing facilitated angioplasty with full- or half-dose thrombolysis versus
      primary angioplasty have been far less favorable with the largest trial to date,
      the ASSENT (Assessment of the Safety and Efficacy of a New Treatment Strategy
      with Percutaneous Coronary Intervention)-4 trial, demonstrating a worse outcome
      in the primary end point of death, congestive heart failure, or shock at 90 days.
      Pending the results of the FINESSE (Facilitated Intervention with Enhanced
      Reperfusion Speed to Stop Events) trial, current data suggest that facilitated
      angioplasty does not offer any advantage over primary angioplasty and may be
      harmful.

PMID- 16978994
TI  - Clinical guidelines and practice: in search of the truth.
AB  - Data from randomized clinical trials, non-randomized studies, and registries, as
      well as expert panel consensus are appropriately weighted and woven into the
      context of clinical practice guidelines. Recent guidelines for the care of
      patients with ischemic heart disease have emphasized both risk stratification and
      early coronary angiography with revascularization of patients with high-risk
      indicators. Advances in our understanding of the pathogenesis of acute coronary
      syndromes and the dynamics of therapeutic innovation (improvement in catheter
      based technologies and adjunctive pharmacotherapy) mandate the timely update and
      revision of practice guidelines. We believe that the weight of evidence remains
      clearly in support of an early invasive treatment strategy based on risk
      stratification. Arguments regarding treatment strategy (invasive vs.
      conservative) are misguided, and greater focus should be placed on improving the
      treatment-risk paradox demonstrated in clinical practice as well as on strategies
      to enhance current guideline compliance and utilization. Interest exists in
      establishing regional centers of excellence for care of patients with acute
      ischemic heart disease, analogous to the regionalized approach already
      established for patients with trauma or stroke. This approach is supported by
      data that demonstrate an inverse relationship between both institutional and
      operator procedural volumes and mortality, as well as by existing constraints in
      resources such as specialized nurses and subspecialty-trained physicians. It is
      appropriate at this time to briefly review specific aspects of the American
      College of Cardiology/American Heart Association practice guidelines and the
      current process of care for acute ischemic heart disease.

PMID- 16978996
TI  - Characterization of plaque prolapse after drug-eluting stent implantation in
      diabetic patients: a three-dimensional volumetric intravascular ultrasound
      outcome study.
AB  - OBJECTIVES: The aim of this research was to evaluate the plaque prolapse (PP)
      phenomenon after bare-metal (BMS) and drug-eluting stent (DES) implantation in
      patients with diabetes mellitus using 3-dimensional volumetric intravascular
      ultrasound (IVUS). BACKGROUND: Plaque prolapse has been observed in up to 22% of
      patients treated with BMS. Diabetic patients have a larger atherothrombotic
      burden and may be more prone to have PP. However, the incidence of PP and its
      clinical impact after DES implantation is unknown. METHODS: Three-dimensional
      IVUS was performed after intervention and at 9-month follow-up in 168 patients
      with diabetes (205 lesions) treated with bare BX Velocity stents ((BX
      Velocity/Sonic, Cordis, Johnson & Johnson) (BMS, n = 65), sirolimus-eluting
      stents (Cypher, Cordis) (SES, n = 69), and paclitaxel-eluting stents (Taxus,
      Boston Scientific, Natick, Massachusetts) (PES, n = 71). Intravascular ultrasound
      data at the sites of PP were compared with stented segments without PP in each
      lesion. Outcomes were evaluated at 9- and 12-month follow-up. RESULTS: There were
      42 sites of PP (BMS = 11, SES = 11, PES = 20, p = NS) in 34 stented segments of
      205 (16.6%) lesions. Plaque prolapse was more frequent in the right coronary
      artery and in chronic total occlusion lesions. Post-procedure PP volume was 1.95
      mm3 in BMS, 2.96 mm3 in SES, and 4.53 mm3 in PES. At follow-up, tissue volume
      increased at PP sites in both BMS and PES, but not after SES. Neointimal
      proliferation was similar between PP and non-PP sites. Stent thrombosis and
      restenosis rates were similar between PP and non-PP lesions. CONCLUSIONS: The
      incidence of PP after implantation of new generation tubular stents in patients
      with diabetes remains high. Drug-eluting stent implantation was not associated
      with increased risk of PP. Plaque prolapse was not associated with stent
      thrombosis or increased neointimal proliferation.

PMID- 16978997
TI  - Troponin-T and N-terminal pro-B-type natriuretic peptide predict mortality
      benefit from coronary revascularization in acute coronary syndromes: a GUSTO-IV
      substudy.
AB  - OBJECTIVES: This study was designed to evaluate biomarkers for selection of
      patients with non-ST-segment elevation acute coronary syndromes (ACS) that derive
      mortality benefit from revascularization. BACKGROUND: Biomarkers are essential
      for identification of patients at increased risk, which may be reduced by
      revascularization. METHODS: During the initial 30 days, 2,340 patients of 7,800
      (30%) with non-ST-segment elevation ACS in the GUSTO (Global Utilization of
      Strategies To open Occluded arteries)-IV trial underwent coronary
      revascularization. The 1-year mortality was calculated in 30-day survivors
      stratified by status of revascularization and levels of biomarkers. A propensity
      score for receiving revascularization was constructed and included in a survival
      analysis that also included the time point of revascularization as a time
      dependent covariate. RESULTS: Elevation of troponin-T or N-terminal pro-B-type
      natriuretic peptide (NT-proBNP) was associated with a high mortality. In patients
      with either or both of these markers elevated, a lower mortality following
      revascularization was observed. In contrast, patients without elevation of these
      markers had low 1-year mortality without any reduction in mortality following
      revascularization. In fact, in patients with normal levels of both troponin-T and
      NT-proBNP, a significant increase in 1-year mortality after revascularization was
      observed. Elevation of C-reactive protein, interleukin-6, creatinine clearance,
      and ST-segment depression was also related to a higher mortality. However,
      independent of these markers, mortality was lower after revascularization.
      CONCLUSIONS: Markers of troponin-T and NT-proBNP not only assist in risk
      stratification of patients with non-ST-segment elevation ACS but also appear to
      identify patients who have a reduced mortality associated with early coronary
      revascularization.

PMID- 16978998
TI  - Plasma adiponectin levels are associated with coronary lesion complexity in men
      with coronary artery disease.
AB  - OBJECTIVES: We sought to assess whether plasma adiponectin levels correlate with
      angiographic coronary lesion complexity in patients with coronary artery disease
      (CAD). BACKGROUND: Metabolic disorders, including diabetes mellitus and metabolic
      syndrome, are important risk factors for acute cardiovascular events, and
      adiponectin is a key molecule of metabolic disorders, with anti-atherogenic
      properties. Low plasma adiponectin levels are associated with CAD and future
      incidence of myocardial infarction. The involvement of adiponectin in coronary
      plaque vulnerability, which may be reflected by angiographic complex lesions,
      remains to be elucidated. METHODS: We measured plasma adiponectin levels in 207
      men (152 with stable CAD and 55 with acute coronary syndromes [ACS]). Coronary
      lesions were classified as of simple or complex appearance. RESULTS: Plasma
      adiponectin levels were significantly lower in stable CAD patients with complex
      coronary lesions (n = 60) than in those with simple lesions (n = 92) (4.14 [range
      2.95 to 6.02] vs. 5.27 [range 3.67 to 8.12] microg/ml, p = 0.006). Multiple
      logistic regression analysis demonstrated that adiponectin level was
      independently associated with complex lesions (odds ratio 0.514, 95% confidence
      interval 0.278 to 0.951; p = 0.034). Polytomous logistic regression revealed that
      adiponectin correlated independently with both single and multiple complex
      lesions. Among patients with ACS, who had lower adiponectin levels than stable
      CAD patients, those with multiple complex lesions had significantly lower
      adiponectin than those with a single complex lesion (3.26 [range 2.26 to 4.46]
      vs. 4.21 [range 3.36 to 5.41] microg/ml, p = 0.032). CONCLUSIONS: Plasma
      adiponectin levels are significantly associated with coronary lesion complexity
      in men with CAD. Low adiponectin levels may contribute to coronary plaque
      vulnerability.

PMID- 16978999
TI  - A big fat wedding: association of adiponectin with coronary vascular lesions.

PMID- 16979000
TI  - The T(-786)C endothelial nitric oxide synthase genotype predicts cardiovascular
      mortality in high-risk patients.
AB  - OBJECTIVES: This study sought to investigate the impact of a common T(-786)C
      single-nucleotide polymorphism (SNP) in the promoter of the endothelial nitric
      oxide synthase (eNOS, NOS3) gene on cardiovascular (CV) death in a prospective
      cohort study. BACKGROUND: The T(-786)C SNP eNOS gene implies a blunted
      endothelium-dependent vasodilation in hypertensive patients and was associated
      with multivessel coronary artery disease in cross-sectional studies, but it
      remained unsettled whether it carried prognostic information. METHODS: In
      consecutive white patients of the GENICA (Genetic and Environmental Factors in
      Coronary Atherosclerosis) study, who underwent coronary angiography between 1999
      and 2001, we determined the incidence of CV death at follow-up. The eNOS T(-786)C
      and the exon 7 G(894)T SNPs were determined by melting curve analysis of
      amplicons from allele-specific fluorescence resonance energy transfer probes.
      Plasma levels of nitrate/nitrite, nitrotyrosine, and myeloperoxidase were also
      measured. The Kaplan-Meier and Cox regression analyses were used to assess the
      impact of SNPs on event-free survival. RESULTS: Complete follow-up data were
      obtained in 1,086 (98%) patients. After a median follow-up of 1,296 days (range 4
      to 2,057 days), we observed 85 (8.2%) CV deaths. There was a significant impact
      of the T(-786)C eNOS genotype on CV death-free (p = 0.0102) survival, but no
      differences in CV death rates across G(894)T genotypes. The TT individuals, who
      showed a lower survival, exhibited higher plasma myeloperoxidase (p < 0.0001) and
      lower levels of nitrotyrosine (p < 0.0001) than CC patients. CONCLUSIONS: The T(
      786)C SNP in the promoter of eNOS bears independent prognostic information and is
      associated with changes in markers of oxidant stress in high-risk white patients
      referred for coronary angiography.

PMID- 16979001
TI  - Significance of vascular nitric oxide synthase pathways in coronary artery
      disease: a multiple-level biomarker strategy.

PMID- 16979002
TI  - Has the risk for coronary heart disease changed among U.S. adults?
AB  - OBJECTIVES: The objective of this study was to compare the 10-year risk of
      developing coronary heart disease (CHD) among U.S adults during the years 1988 to
      1994 with that among U.S. adults during the years 1999 to 2002. BACKGROUND: A
      decline in deaths as the result of CHD has been reported. Data about changes in
      actual risk of developing CHD among U.S. adults are sparse. METHODS: Data for
      noninstitutionalized U.S. residents ages 20 to 79 years who participated in the
      National Health and Nutrition Examination Survey (NHANES)-III (1988 to 1994) or
      NHANES 1999 to 2002 were examined to compute 10-year risk of developing CHD using
      modified Framingham risk score, as adopted by the National Cholesterol Education
      Program, Adult Treatment Panel III. RESULTS: Most participants in both surveys
      had a low (<10%) 10-year risk of developing CHD. The proportion of participants
      at intermediate (10% to 20%) and high (>20%) 10-year risk of developing CHD also
      was similar. CONCLUSIONS: Data from national surveys conducted approximately a
      decade apart showed no appreciable difference in the distribution of 10-year risk
      of developing CHD. Greater efforts are needed to reduce the risk of developing
      CHD among U.S. adults.

PMID- 16979003
TI  - Cardiovascular risk among adults with chronic kidney disease, with or without
      prior myocardial infarction.
AB  - OBJECTIVES: This study sought to determine whether chronic kidney disease (CKD)
      should be considered a coronary heart disease (CHD) risk equivalent for
      cholesterol treatment. BACKGROUND: It is unclear whether patients with CKD have a
      risk of CHD events or cardiovascular disease (CVD) mortality equivalent to
      patients with a prior myocardial infarction (MI). METHODS: Using data from the
      ARIC (Atherosclerosis Risk in Communities) study, we categorized nondiabetic
      participants based on their average level of kidney function (estimated
      glomerular filtration rate > or =60 or 30 to 59 ml/min/1.73 m2, which defines
      stage 3 CKD) and on prior MI (yes or no). Rates and relative risks (RR) of CHD
      (MI or fatal CHD) events (n = 653) and CVD mortality (n = 209) that occurred over
      10 years were compared across these populations. RESULTS: Among 12,243 middle-age
      participants, 271 had stage 3 CKD. After adjustment for age, gender, race, and
      center, CHD incidence and CVD mortality rates per 1,000 person-years by presence
      of CKD and MI were 4.1 and 1.0 in the presence of neither condition, 8.0 and 3.4
      in CKD only, 18.8 and 7.0 in MI only, and 30.8 and 18.0 in CKD and MI. After
      further adjustment for CVD risk factors, RR of CHD and CVD mortality were
      statistically significantly lower in subjects with CKD and no prior MI (RR = 0.44
      [95% confidence interval (CI) 0.28 to 0.72] for CHD and RR = 0.46 [95% CI 0.24 to
      0.90] for CVD mortality) than for subjects with no CKD and a prior MI.
      CONCLUSIONS: Stage 3 CKD confers CHD risk that is lower and not equivalent to a
      prior MI in this middle-aged, general, nondiabetic population.

PMID- 16979004
TI  - The effect of novel cardiovascular risk factors on the ethnic-specific odds for
      peripheral arterial disease in the Multi-Ethnic Study of Atherosclerosis (MESA).
AB  - OBJECTIVES: The purpose of this study was to: 1) determine the significance and
      magnitude of associations between novel cardiovascular disease (CVD) risk factors
      and peripheral arterial disease (PAD) after adjustment for traditional risk
      factors; and 2) ascertain the extent to which novel risk factors explain the
      excess or lower risk for PAD in different ethnic groups. BACKGROUND: Previous
      reports have found a significant difference in the risk of PAD by ethnic group,
      with some of the risk difference attributed to different levels of traditional
      CVD risk factors. METHODS: A total of 6,814 individuals free of clinically
      apparent CVD were enrolled in the MESA (Multiethnic Study of Atherosclerosis) and
      underwent standardized testing for the presence of PAD by the ankle-brachial
      index. These subjects also had fasting blood drawn for serum cholesterol,
      glucose, and a number of novel biomarkers for CVD. Non-Hispanic whites were the
      largest ethnic group (38%), followed by African Americans (28%), Hispanics (22%),
      and Chinese (12%). RESULTS: In this cross-sectional analysis, 6,653 subjects with
      an ankle brachial index <1.40 were analyzed. The mean (SD) age was 62.2 (10.2)
      years, and 52.9% were women. Interleukin-6, fibrinogen, D-dimer, and homocysteine
      were significantly associated with PAD after adjustment for traditional CVD risk
      factors. Compared with non-Hispanic whites and after adjustment for traditional
      and "novel" risk factors, the odds for PAD were 1.47 (95% confidence interval
      [CI]: 1.07 to 2.02) times higher in African Americans, while being 0.45 (95% CI:
      0.29 to 0.70) and 0.44 (95% CI: 0.24 to 0.78) in Hispanics and Chinese,
      respectively. CONCLUSIONS: Ethnic associations with PAD remained significant even
      after adjustment for traditional and novel risk factors. This suggests that
      unknown factors may account for the residual ethnic differences in PAD.

PMID- 16979005
TI  - Enhanced external counterpulsation improves exercise tolerance in patients with
      chronic heart failure.
AB  - OBJECTIVES: The PEECH (Prospective Evaluation of Enhanced External
      Counterpulsation in Congestive Heart Failure) study assessed the benefits of
      enhanced external counterpulsation (EECP) in the treatment of patients with mild
      to-moderate heart failure (HF). BACKGROUND: Enhanced external counterpulsation
      reduced angina symptoms and extended time to exercise-induced ischemia in
      patients with coronary artery disease, angina, and normal left ventricular
      function. A small pilot study and registry analysis suggested benefits in
      patients with HF. METHODS: We randomized 187 subjects with mild-to-moderate
      symptoms of HF to either EECP and protocol-defined pharmacologic therapy (PT) or
      PT alone. Two co-primary end points were pre-defined: the percentage of subjects
      with a 60 s or more increase in exercise duration and the percentage of subjects
      with at least 1.25 ml/min/kg increase in peak volume of oxygen uptake (VO2) at 6
      months. RESULTS: By the primary intent-to-treat analysis, 35% of subjects in the
      EECP group and 25% of control subjects increased exercise time by at least 60 s
      (p = 0.016) at 6 months. However, there was no between-group difference in peak
      VO2 changes. New York Heart Association (NYHA) functional class improved in the
      active treatment group at 1 week (p < 0.01), 3months (p < 0.02), and 6 months (p
      < 0.01). The Minnesota Living with Heart Failure score improved significantly 1
      week (p < 0.02) and 3 months after treatment (p = 0.01). CONCLUSIONS: In this
      randomized, single-blinded study, EECP improved exercise tolerance, quality of
      life, and NYHA functional classification without an accompanying increase in peak
      VO2.

PMID- 16979006
TI  - Enhanced external counterpulsation: what can we learn from the treatment of
      neurasthenia?

PMID- 16979007
TI  - Enhanced external counterpulsation treatment improves arterial wall properties
      and wave reflection characteristics in patients with refractory angina.
AB  - OBJECTIVES: To determine if arterial properties and wave reflection
      characteristics are favorably altered after enhanced external counterpulsation
      (EECP) treatment in patients with refractory angina. BACKGROUND: Early return of
      reflected waves from the lower body, resulting from increased arterial stiffness,
      augments central aortic pressure and increases left ventricular (LV) afterload
      and myocardial oxygen demand. EECP acutely enhances coronary perfusion (supply)
      and reduces LV afterload (demand). However, the mechanisms responsible for the
      sustained beneficial effects of EECP treatment are unclear. METHODS: Radial
      artery pressure waveforms were recorded by applanation tonometry and central
      aortic pressure waveforms generated using a mathematical transfer function in 20
      patients with stable refractory angina. Data were collected before and after 34 1
      h EECP sessions. Augmentation index (AI(a)) and timing of the reflected pressure
      wave were calculated from the aortic waveform. RESULTS: EECP treatment caused a
      decline in AI(a) and an increase in reflected wave travel time. These
      modifications in wave reflection characteristics caused a decrease in aortic
      systolic pressure and wasted LV pressure energy. The average number of angina
      episodes and Canadian Cardiovascular Society (CCS) class, both decreased in
      concordance with the physiologic changes due to EECP treatment. CONCLUSIONS: EECP
      treatment reduces arterial stiffness and improves wave reflection characteristics
      in patients with refractory angina. These changes decrease LV afterload and
      myocardial oxygen demand and reduce the number of angina episodes, therefore
      enabling patients to participate in continuous exercise programs which in turn
      may provide long-term benefits and sustained improved quality of life.

PMID- 16979008
TI  - Enhanced external counterpulsation why the benefit?

PMID- 16979009
TI  - Utility of amino-terminal pro-brain natriuretic peptide, galectin-3, and apelin
      for the evaluation of patients with acute heart failure.
AB  - OBJECTIVES: This study sought to explore the role of new biomarkers in heart
      failure (HF). BACKGROUND: We investigated the utility of novel serum markers
      alone or together with natriuretic peptide testing for diagnosis and short-term
      prognosis estimation in subjects with acute HF. METHODS: Plasma levels of amino
      terminal pro-brain natriuretic peptide (NT-proBNP), apelin, and galectin-3 were
      measured in 599 patients presenting with dyspnea at the emergency department, of
      which 209 (35%) had acute HF. RESULTS: The NT-proBNP was superior to either
      apelin or galectin-3 for diagnosis of acute HF, although galectin-3 levels were
      significantly higher in subjects with HF compared with those without. Receiver
      operating characteristic analysis for mortality prediction showed that, for 60
      day prognosis, galectin-3 had the greatest area under the curve (AUC) at 0.74 (p
      = 0.0001), whereas NT-proBNP and apelin had an AUC of 0.67 (p = 0.009) and 0.54
      (p = 0.33). In a multivariate logistic regression analysis, an elevated level of
      galectin-3 was the best independent predictor of 60-day mortality (odds ratio
      10.3, p < 0.01) or the combination of death/recurrent HF within 60 days (odds
      ratio 14.3, p < 0.001). The Kaplan-Meier analyses showed that the combination of
      an elevated galectin-3 with NT-proBNP was a better predictor of mortality than
      either of the 2 markers alone. CONCLUSIONS: Our data show potential utility of
      galectin-3 as a useful marker for evaluation of patients with suspected or proven
      acute HF, whereas apelin measurement was not useful for these indications.
      Moreover, the combination of galectin-3 with NT-proBNP was the best predictor for
      prognosis in subjects with acute HF.

PMID- 16979010
TI  - Intravenous iron alone for the treatment of anemia in patients with chronic heart
      failure.
AB  - OBJECTIVES: This study was undertaken to assess the hematologic, clinical, and
      biochemical response to intravenous iron in patients with chronic heart failure
      (CHF) and anemia. BACKGROUND: Anemia is common in patients with CHF and is
      associated with higher morbidity and mortality. The combination of erythropoietin
      (EPO) and iron increases hemoglobin (Hb) and improves symptoms and exercise
      capacity in anemic CHF patients. It is not known whether intravenous iron alone
      is an effective treatment for anemia associated with CHF. METHODS: Sixteen anemic
      patients (Hb < or =12 g/dl) with stable CHF (age 68.3 +/- 11.5 years, 12 men, 9
      participants New York Heart Association [NYHA] functional class II and the
      remainder class III, left ventricular ejection fraction 26 +/- 13%) received a
      maximum of 1 g of iron sucrose by bolus intravenous injections over a 12-day
      treatment phase in an outpatient setting. Mean follow-up was 92 +/- 6 days.
      RESULTS: Hemoglobin rose from 11.2 +/- 0.7 to 12.6 +/- 1.2 g/dl (p = 0.0007),
      Minnesota Living with Heart Failure (MLHF) score fell (denoting improvement) from
      33 +/- 19 to 19 +/- 14 (p = 0.02), 6-min walk distance increased from 242 +/- 78
      m to 286 +/- 72 m (p = 0.01), and all patients recorded NYHA class II at study
      end (p < 0.02). Changes in MLHF score and 6-min walk distance related closely to
      changes in Hb (r = 0.76, p = 0.002; r = 0.56, p = 0.03, respectively). Of all
      baseline measurements, only iron and transferrin saturation correlated with
      increases in Hb (r = 0.60, p = 0.02; r = 0.60, p = 0.01, respectively). There
      were no adverse events relating to drug administration or during follow-up.
      CONCLUSIONS: Intravenous iron sucrose, when used without concomitant EPO, is a
      simple and safe therapy that increases Hb, reduces symptoms, and improves
      exercise capacity in anemic patients with CHF. Further assessment of its efficacy
      should be made in a multicenter, randomized, placebo-controlled trial.

PMID- 16979011
TI  - Effects of statin therapy on arrhythmic events and survival in patients with
      nonischemic dilated cardiomyopathy.
AB  - OBJECTIVES: We sought to evaluate whether statins were associated with a survival
      benefit and significant attenuation in life-threatening arrhythmias in patients
      with nonischemic dilated cardiomyopathy. BACKGROUND: Statins are associated with
      a reduction in appropriate implantable cardioverter-defibrillator (ICD) therapy
      in patients with coronary artery disease and improved clinical status in
      nonischemic dilated cardiomyopathy. METHODS: The effect of statin use on time to
      death or resuscitated cardiac arrest and time to arrhythmic sudden death was
      evaluated in 458 patients enrolled in the DEFINITE (DEFIbrillators in Non
      Ischemic cardiomyopathy Treatment Evaluation) study. The effect of statin use on
      time to first appropriate shock was analyzed only in the 229 patients who were
      randomized to ICD therapy. RESULTS: The unadjusted hazard ratio (HR) for death
      among patients on versus those not on statin therapy was 0.22 (95% confidence
      interval [CI] 0.09 to 0.55; p = 0.001). When controlled for statin effects, ICD
      therapy was associated with improved survival (HR 0.61; 95% CI 0.38 to 0.99; p =
      0.04). There was one arrhythmic sudden death in the 110 patients receiving statin
      therapy (0.9%) versus 18 of 348 patients not receiving statins (5.2%; p = 0.04).
      The unadjusted HR for arrhythmic sudden death among patients on versus those not
      on statin therapy was 0.16 (95% CI 0.022 to 1.21; p = 0.08). The HR for
      appropriate shocks among patients on versus those not on statin therapy was 0.78
      (95% CI 0.34 to 1.82) after adjustment for baseline differences in the two
      groups. CONCLUSIONS: Statin use in the DEFINITE study was associated with a 78%
      reduction in mortality. This reduction was caused, in part, by a reduction in
      arrhythmic sudden death. These findings should be confirmed in a prospective,
      randomized clinical trial.

PMID- 16979012
TI  - Attenuation of the negative inotropic effects of metoprolol at short cycle
      lengths in humans: comparison with sotalol and verapamil.
AB  - OBJECTIVES: This study sought to compare the influence of changes in systolic
      interval on the negative inotropic effects of metoprolol, sotalol, and verapamil
      in patients with ischemic heart disease. BACKGROUND: The long-term symptomatic
      and prognostic effects of antiarrhythmic agents are not easily predicted on the
      basis of acute hemodynamic actions at rest, but may be unmasked during
      tachycardia. However, this has not been studied extensively in vivo. METHODS: The
      force-interval relationship of the intact human left ventricle was examined
      before and 10 min after intravenous bolus administration of the negatively
      inotropic agents metoprolol, sotalol, or verapamil in patients undergoing
      diagnostic cardiac catheterization. RESULTS: All three drugs similarly reduced
      maximal rate of increase of left ventricular pressures (LV+dP/dt(max)) by
      approximately 10%, but diversely modified the force-interval relationship. The
      parameter c (the reduction in LV+dP/dt(max) of a fixed premature stimulus on
      mechanical restitution) was significantly reduced by metoprolol (by 9+/- 4%, p <
      0.05), was increased by verapamil (by 6 +/- 2%, p < 0.05), and was not
      significantly changed by sotalol. Similarly, metoprolol had a minimal effect on
      the extent of frequency potentiation, whereas sotalol and verapamil attenuated
      frequency potentiation (the relative response to 10 s of rapid pacing was 1.19 +/
      0.58-fold, 0.07 +/- 0.35-fold, and 0.03 +/- 0.17-fold of the baseline response
      after 10 min of metoprolol, sotalol, or verapamil, respectively). CONCLUSIONS:
      These results show that the negative inotropic effects of metoprolol are
      attenuated and those of verapamil are accentuated at short cycle lengths; sotalol
      is intermediate between the two. These properties may contribute to the relative
      safety of these agents in patients prone to hemodynamic deterioration during
      sustained tachycardia.

PMID- 16979013
TI  - The effects of carbenoxolone on human myocardial conduction: a tool to
      investigate the role of gap junctional uncoupling in human arrhythmogenesis.
AB  - OBJECTIVES: This study assessed the effects of carbenoxolone on human myocardial
      conduction and refractoriness. BACKGROUND: Carbenoxolone, an antipeptic ulcer
      drug, has been shown to reduce gap junctional coupling without affecting cellular
      ion channels. Gap junctions (GJ) are considered to be determinants of cardiac
      action potential propagation. The effects of GJ uncoupling in the human heart are
      unknown. METHODS: Right atrial (RA) and ventricular (RV) activation mapping
      (Carto, Biosense Webster Inc., Diamond Bar, California) was performed during
      sinus rhythm. Right atrial and RV wavefront propagation velocity (WPV),
      specifically in the direction of propagation, was determined from these maps
      using a triangulation method. Refractoriness at multiple RA and RV sites, sinus
      rhythm cycle length, and AH, PR, QRS, and QT intervals were measured. The
      protocol was repeated 1 h after oral administration of 100 mg of carbenoxolone.
      RESULTS: In 11 patients, WPV was reduced from 79.6 +/- 13.3 cm/s to 57.2 +/- 9.1
      cm/s (-27.1 +/- 12.8%, p < 0.001) in RA and from 98.7 +/- 19.8 cm/s to 76.5 +/-
      21.7 cm/s (-22.7 +/- 14.1%, p < 0.01) in RV after carbenoxolone. Conduction
      slowing was more marked in 6 older patients with ischemic heart disease compared
      with younger subjects with normal hearts (RA -35.1 +/- 5.5% vs. -17.5 +/- 12.7%,
      p = 0.03; RV -33.8 +/- 5.1% vs. -9.3 +/- 7.7%, p < 0.001). Refractoriness and
      electrocardiogram parameters remained unchanged. CONCLUSIONS: Carbenoxolone
      causes a 27% reduction in human RA WPV and 23% in the RV without affecting
      refractoriness. The slowing of myocardial conduction by carbenoxolone
      demonstrates the significance of GJ in regulating human myocardial conduction and
      provides a tool for investigating the effects of GJ uncoupling on human
      arrhythmogenesis.

PMID- 16979014
TI  - Heart rate response during exercise predicts survival in adults with congenital
      heart disease.
AB  - OBJECTIVES: To assess the prognostic value of heart rate response to exercise in
      adult congenital heart disease (ACHD) patients. BACKGROUND: An abnormal heart
      rate response to exercise is related to autonomic dysfunction and may have
      prognostic implications in ACHD. METHODS: We identified 727 consecutive ACHD
      patients (mean age [+/- SD] 33 +/- 13 years) with varying diagnoses and without
      pacemakers. Peak oxygen consumption (peak VO2), resting heart rate, and the
      increase in heart rate from resting level to peak exercise ("heart rate reserve")
      were measured. We also quantified the decrease in heart rate ("heart rate
      recovery") after cessation of exercise. RESULTS: During a median follow-up of 28
      months, 38 patients died. Lower values of heart rate reserve, peak heart rate,
      heart rate recovery, and peak VO2 (p < 0.01 for each) were associated with
      increased mortality in univariate analysis. Furthermore, heart rate reserve
      predicted mortality independently of antiarrhythmic therapy, functional class,
      and peak VO2. Stratifying patients by diagnostic groups revealed that a lower
      heart rate reserve was also associated with a greater risk of death in patients
      with complex anatomy, Fontan circulation, and tetralogy of Fallot (p < 0.05 for
      each). CONCLUSIONS: An abnormal heart rate response to exercise identifies ACHD
      patients with a higher risk of mortality in the midterm, even after accounting
      for antiarrhythmic medication and exercise capacity. Heart rate reserve is a
      simple and inexpensive way to identify ACHD patients at higher mortality risk.

PMID- 16979015
TI  - Expression of myeloid-related protein-8 and -14 in patients with acute Kawasaki
      disease.
AB  - OBJECTIVES: This study investigated patients with acute Kawasaki disease (KD) to
      validate myeloid-related protein (MRP)-8/MRP-14 as a marker of disease activity
      and severity of coronary artery lesion development. BACKGROUND: Both MRP-8 and 
      14, which are S100-proteins secreted by activated neutrophils and monocytes, bind
      specifically to endothelial cells and induce thrombogenic and inflammatory
      responses in a variety of disease conditions. METHODS: We investigated 61
      patients with acute KD and examined sequential changes in serum levels of MRP
      8/MRP-14, messenger ribonucleic acid (mRNA) expression of MRP-8 and -14 in
      circulating granulocytes and monocytes, and amounts of MRP-8/MRP-14 bound to
      circulating endothelial cells. RESULTS: The serum MRP-8/MRP-14 levels as well as
      mRNA expressions of MRP-8 and -14 in granulocytes were strongly upregulated
      during the early stage of acute KD, and decreased dramatically within 24 h of
      intravenous immune globulin therapy (p < 0.05) in 45 responders. In contrast, in
      16 nonresponders both of these increased after the initial treatment. The number
      of MRP-8/MRP-14-positive circulating endothelial cells was higher in patients
      with acute KD than in control patients and increased significantly by 2 weeks
      after the onset of KD, especially in patients in whom coronary artery lesions
      developed. CONCLUSIONS: We show for the first time that MRP-8/MRP-14 are
      exclusively secreted by granulocytes in patients with acute KD, and intravenous
      immune globulin treatment suppresses their gene expression. Serum levels of MRP
      8/MRP-14 may be useful markers of disease activity, and the levels of MRP-8/MRP
      14-positive circulating endothelial cell may predict the severity of vasculitis,
      confirming an important role for distinct inflammatory reactions in endothelium.

PMID- 16979016
TI  - S100 proteins in the pathogenesis of Kawasaki disease.

PMID- 16979017
TI  - Beat-to-Beat variability of repolarization determines proarrhythmic outcome in
      dogs susceptible to drug-induced torsades de pointes.
AB  - OBJECTIVES: We investigated whether increasing or decreasing beat-to-beat
      variability of repolarization (BVR) would change drug-induced proarrhythmic
      outcome accordingly. BACKGROUND: Increased variability of repolarization has been
      suggested as a prelude to proarrhythmic circumstances in experimental and
      clinical situations. METHODS: The non-cardiovascular, I(Kr)-blocking drug
      sertindole was administered to anesthetized dogs with chronic atrioventricular
      block. Three interventions were used to prevent or suppress sertindole-induced
      torsades de pointes (TdP). RESULTS: Supratherapeutic doses of sertindole (1.0
      mg/kg intravenously) induced TdP in 10 of 13 dogs whereas 0.2 mg/kg induced no
      TdP, despite increases in QT intervals by both doses. The BVR, quantified as
      short-term variability (STV) from Poincare plots, was the only parameter that
      predicted TdP outcome (1.0 mg/kg sertindole: 2.3 +/- 0.7 ms to 5.1 +/- 2.1 ms, p
      < 0.05; 0.2 mg/kg sertindole: 2.3 +/- 0.8 ms to 3.2 +/- 1.1 ms, p= NS).
      INTERVENTIONS: 1) KCl, intravenous, reduced the incidence of sertindole-induced
      TdP from 6 of 7 to 1 of 7 dogs (p<0.05) and prevented sertindole-related increase
      of STV: 3.0 +/- 1.1 ms vs. 4.5 +/- 1.3 ms (p < 0.05); 2) levcromakalim (I(K,ATP)
      activator) reduced sertindole-induced TdP and decreased STV from 4.9 +/- 2.1 ms
      to 2.6 +/- 0.9 ms (p < 0.05); 3) steady-state ventricular pacing (60 beats/min)
      abolished sertindole-induced TdP and decreased STV from 4.9 +/- 1.5 to 3.2 +/-
      1.0 (p < 0.05). Torsades de pointes reappeared upon return to non-paced
      idioventricular rhythm. None of the 3 interventions reduced the sertindole
      induced prolonged QT interval. CONCLUSIONS: Proarrhythmic intervention is related
      to an increase in BVR, whereas antiarrhythmic treatment is associated with a
      decrease in BVR. The BVR is superior to QT interval prolongation in the
      prediction and prevention of drug-induced TdP in this experimental model.

PMID- 16979018
TI  - Aldosterone synthase promoter polymorphism predicts outcome in African Americans
      with heart failure: results from the A-HeFT Trial.
AB  - OBJECTIVES: We sought to evaluate the effect of the aldosterone synthase promoter
      polymorphism on heart failure outcomes for subjects in the African American Heart
      Failure Trial (A-HeFT). BACKGROUND: Genetic heterogeneity modulates clinical
      outcomes in subjects with heart failure (HF); however, little data exist in
      African American populations. A common polymorphism exists in the promoter region
      of the aldosterone synthase gene (CYP11B2) at position -344 (T/C). The -344C
      allele, associated with higher aldosterone synthase activity, has been linked to
      hypertension; however, its impact on outcomes in HF is unknown. METHODS: A total
      of 354 subjects from A-HeFT participated in the GRAHF (Genetic Risk Assessment of
      Heart Failure in African Americans) substudy and were genotyped for the
      aldosterone synthase polymorphism. Patients were followed prospectively, and
      event-free survival (freedom from death and HF hospitalization) compared by
      CYP11B2 genotype. RESULTS: Of the cohort, 218 patients were TT, 114 CT, and 22
      patients were CC. Baseline etiology, blood pressure, and functional class were
      not significantly different among the 3 cohorts. The C allele was associated with
      significantly poorer HF hospitalization-free survival with the best survival
      among TT subjects, intermediate for heterozygotes, and the poorest for CC
      homozygotes (p = 0.018), and a higher rate of death (% death TT/TC/CC =
      1.8/3.5/18.2, p = 0.001). The TT genotype, more prevalent in blacks, was
      associated with greater impact of fixed combination of isosorbide dinitrate and
      hydralazine on the primary composite end point (p = 0.01). CONCLUSIONS: The
      aldosterone synthase promoter -344C allele linked to higher aldosterone levels is
      associated with poorer event-free survival in blacks with HF. The role of
      aldosterone receptor antagonists in diminishing this apparent genetic risk
      remains to be explored.

PMID- 16979019
TI  - Atorvastatin in nonischemic left ventricular systolic dysfunction.

PMID- 16979020
TI  - Cost-effectiveness of cardiac resynchronization therapy.

PMID- 16979021
TI  - Beta-blockers and exercise.

PMID- 16979024
TI  - Standard Deviation of Sequential Five-Minute R-R Interval Means (SDANN) is a
      prognostic marker, but not necessarily an autonomic marker.

PMID- 16979026
TI  - Use of the Allen's test and transradial catheterization.

PMID- 16979027
TI  - Is the Allen's test accurate for patients considered for transradial coronary
      angiography?

PMID- 16979030
TI  - Pathology of inflammatory native valvular heart disease.
AB  - Rheumatic disease is an important cause of inflammatory native heart valve
      disease. However, with increased understanding of the pathoetiology of valve
      disease and valve injury, it is evident that inflammation may play a role in many
      valve disorders. We are only beginning to understand these complex processes.
      With increasing knowledge that many of these processes are active, there may be
      opportunity for intervention or even prevention.

PMID- 16979031
TI  - Pathology of infectious and inflammatory diseases in prosthetic heart valves.
AB  - Prosthetic heart valves, both mechanical and biological (xenograft valves,
      stented or unstented), show an inflammatory reaction (infective endocarditis),
      associated predominantly with bacterial/fungal infection. Somewhat surprisingly,
      no immune-mediated reaction has been reported thus far. This may, among other
      reasons, be related to the fact that the tissues are "fixed" with aldehydes and
      are virtually isolated from host circulation, separated by synthetic material
      (the valve stent and the fabric covering it). Stentless valves (especially these
      without fabric covering them), however, have no such "isolation" from the host
      circulation. While the Toronto-Stentless Porcine Valve has a covering of fabric,
      the Medtronic Freestyle valve has no such covering. It is perhaps not so
      surprising therefore that at the intermediate time point of 5 to 6 years, some
      valves are beginning to show such an immune reaction.

PMID- 16979032
TI  - Pathology and pathogenesis of infective endocarditis in native heart valves.
AB  - Infective endocarditis is an endovascular microbial infection of cardiovascular
      structures, including large intrathoracic vessels and intracardiac foreign
      bodies. The characteristic lesions consist of vegetations composed of platelets,
      fibrin, microorganisms, and inflammatory cells, as well as leaflet disruption.
      The commonly accepted pathogenetic theory is herein reported, from endothelial
      injury with deposition of noninfective sterile thrombotic vegetations to
      transient bacteremia with microorganism adhesion (injury-thrombus-infection
      theory). This review addresses the pathology of native valve endocarditis,
      including local (valvular and perivalvular destruction) and distal (embolism,
      metastatic infection, and septicemia) complications. Old and new cardiac
      conditions and patients at risk, predisposing to the occurrence of infective
      endocarditis, are then discussed. Particular emphasis is given to hidden bicuspid
      aortic valve and the need of early carrier identification for prophylaxis.

PMID- 16979033
TI  - Infection in ventricular assist devices: the role of biofilm.
AB  - Ventricular assist devices improve hemodynamics in patients with heart failure,
      but like most implantable medical devices, they are prone to infection; organisms
      that are adept at forming biofilm cause most of these. Biofilm confers many
      advantages to the organisms, including protecting them against natural host
      defenses and antimicrobial therapies. This review will focus on the mechanisms of
      biofilm formation, including quorum sensing and subsequent changes in microbial
      gene and protein expression. Novel therapies targeting these processes, as well
      as improvements in device design and clinical management, have begun to emerge
      and will aid in the management of these recalcitrant infections.

PMID- 16979034
TI  - New frontiers in the pathology and therapy of heart valve disease: 2006 Society
      for Cardiovascular Pathology, Distinguished Achievement Award Lecture, United
      States-Canadian Academy of Pathology, Atlanta, GA, February 12, 2006.
AB  - This review summarizes several areas relative to the pathology of heart valve
      disease in which there has been rapid and ongoing evolution, namely, our
      understanding of: (a) the dynamic functional biology of cardiac valves; and (b)
      the pathology/pathobiology of valvular heart diseases; (c) new developments in
      valve repair and substitution using percutaneous approaches; and (d) progress
      toward the exciting potential of therapeutic valvular tissue engineering and
      regeneration, including the challenges that will need to be overcome before such
      therapeutic advances can become clinically useful.

PMID- 16979035
TI  - Failure to detect human herpes simplex virus, cytomegalovirus, and Epstein-Barr
      virus viral genomes in giant cell arteritis biopsy specimens by real-time
      quantitative polymerase chain reaction.
AB  - A study provided evidence of human herpes simplex virus (HSV) DNA in giant cell
      arteritis (GCA) biopsy specimens. This prompted us to study our own GCA biopsy
      specimens using real-time quantitative polymerase chain reaction for the
      detection of HSV1, cytomegalovirus, and Epstein-Barr virus DNAs. Our study failed
      to confirm an association between HSV1 and GCA, revealing no viral genome in 35
      biopsy specimens of histologically positive temporal arteries.

PMID- 16979036
TI  - Patterns of isolated atrial amyloid: a study of 100 hearts on autopsy.
AB  - Isolated atrial amyloid (IAA), one of the most common members of the family of
      age-related ("senile") amyloids, seems to play a role in the pathogenesis of
      atrial fibrillation. Patterns of IAA deposition were histologically studied in
      the hearts of 100 elderly patients. The incidence (%) and severity (grade 0-3) of
      atrial IAA deposits increase with age, from 75% incidence and 0.50 average grade
      in patients aged 51-60 years, to 86% incidence and 1.49 average grade in those
      aged 81-90 years. Deposits are more pronounced in females (88% incidence, 1.45
      average grade) than in males (68% incidence, 0.79 average grade). Left atrial
      deposits are more pronounced (78% incidence, 1.25 average grade) than right
      atrial deposits (67% incidence, 1.09 average grade). The distribution of IAA in
      the walls of the left atrium is uneven, with deposits being more pronounced in
      the anterior wall than in both the posterior wall and the left appendage. IAA
      deposits are heavier (1.34 average grade) in patients with chronic atrial
      fibrillation than in those with sinus rhythm (1.01 average grade); the
      difference, however, lacks statistical significance. Hypertension, diabetes
      mellitus, hypertrophy of the heart, coronary atherosclerosis, and dilatation of
      the atria show no significant relationship to the incidence or severity of atrial
      amyloidosis.

PMID- 16979037
TI  - Ruptured sinus of Valsalva aneurysm complicated by myocardial ischemia:
      pathogenetic mechanisms.
AB  - Significant left-to-right shunt in combination with severe aortic regurgitation
      (AR) accelerates the development of symptoms after rupture of congenital sinus of
      Valsalva aneurysm (SVA) in spite of intact coronary arteries. We depict a rare
      description of a situation where acute coronary syndrome was the first
      manifestation of such an occurrence. We believe that the progress of the
      myocardial ischemia after ruptured SVA depends on the severity of AR and the
      quantity of the left-to-right shunt. Prompt recognition and surgical repair are
      indicated to prevent complications of myocardial infarction.

PMID- 16979038
TI  - Ascending aortic aneurysm in a fetus due to a benign nodular myofibroblastic
      lesion.
AB  - A fetal echocardiogram at 20 weeks of gestation revealed a large ascending aortic
      aneurysm in the presence of a normal aortic root and normal intracardiac anatomy.
      No other abnormalities were noted in the fetus. Upon termination of pregnancy,
      histopathological examination revealed an isolated benign nodular myofibroblastic
      lesion of likely hamartomatous origin, a first description of such pathology
      contributing to the formation of an aneurysm in the ascending aorta.

PMID- 16979039
TI  - Sternum osteolysis following staphylococcus mediastinitis.

PMID- 16979040
TI  - Fatal outcome of a calcified amorphous tumor of the heart (cardiac CAT).
AB  - Calcified amorphous tumor of the heart (cardiac CAT) is an unusual non-neoplastic
      cardiac mass that can mimic a more malignant lesion. We describe a case of
      cardiac CAT in a 60-year-old female who presented with syncope. Workup revealed a
      2.1-cm mass in the right ventricular wall involving the chordae tendineae of the
      tricuspid valve, impacting right ventricular function. Magnetic resonance
      imaging, echocardiography, angiography, and histologic descriptions of the lesion
      are described.

PMID- 16979041
TI  - A symptomatic coracoclavicular joint successfully treated by surgical excision.

PMID- 16979042
TI  - Loss of pectoral muscles: treatment with latissimus dorsi muscle rotational flap.

PMID- 16979043
TI  - Avulsion of the lesser tuberosity with a Salter-Harris type II injury of the
      proximal humerus: a case report.

PMID- 16979044
TI  - Anteromedial fracture of the coronoid process of the ulna.

PMID- 16979045
TI  - Bipolar-type floating radial head prosthesis for the treatment of giant cell
      tumor of the proximal radius: a case report.

PMID- 16979046
TI  - Neer Award 2005: The Grammont reverse shoulder prosthesis: results in cuff tear
      arthritis, fracture sequelae, and revision arthroplasty.
AB  - This clinical study was performed to analyze the midterm results and potential
      complications of the reverse prosthesis in different diagnosis. Forty-five
      consecutive patients with Grammont prosthesis were evaluated clinically and
      radiographically with a mean follow-up of 40 months (range, 24-72 months). The
      indication was a massive and irreparable cuff tear associated with arthrosis
      (CTA) in 21 cases, fracture sequelae (FS) with arthritis in 5 cases, and failure
      of a revision arthroplasty (revision) in 19 cases. Fourteen complications
      occurred in 11 patients. 3 dislocations, 3 deep infections (all 3 in the revision
      group), 1 case of aseptic humeral loosening, 2 periprosthetic humeral fractures,
      1 intraoperative glenoid fracture, 1 wound hematoma, 2 late acromial fractures,
      and 1 axillary nerve palsy. Of the patients, 10 (22%) required further surgery: 4
      reoperations, 4 prosthesis revisions, and 2 prosthesis removals. Complications
      were higher in revision than in CTA (47% vs. 5%). All 3 groups showed a
      significant increase in active elevation (from 55 degrees preoperatively to 121
      degrees postoperatively) and Constant score (from 17 to 58 points) but no
      significant change in active external rotation (from 7 degrees to 11 degrees ) or
      internal rotation (S1 preoperatively and postoperatively). Of the patients, 78%
      were satisfied or very satisfied with the result and 67% had no or slight pain.
      However, the postoperative Constant score, adjusted Constant score, and American
      Shoulder and Elbow Surgeons shoulder score were all significantly higher in the
      CTA group with as compared with the revision group (P = .01, .004, and .002,
      respectively). Scapular notching was seen in 24 cases (68%). No glenoid loosening
      was observed at current follow-up, even when the notch extended beyond the
      inferior screw (28% of cases). Atrophy of severe fatty infiltration of the teres
      minor was associated with lower external rotation (15 degrees vs 0 degrees , P =
      .02) and lower functional results (Constant score of 46 points vs 66 points, P <
      .007). The Grammont reverse prosthesis can improve function and restore active
      elevation in patients with incongruent cuff-deficient shoulders; active rotation
      is usually unchanged. Results are less predictable and complication and revision
      rates are higher in patients undergoing revision surgery as compared with those
      in patients with CTA. Results of the reverse prosthesis depend on the diagnosis
      and on the remaining cuff muscles, specifically the teres minor. Surgeons should
      be vigilant with regard to low-grade infection in revision surgery.

PMID- 16979047
TI  - Ultrasound evaluation and clinical correlation of subscapularis repair after
      total shoulder arthroplasty.
AB  - The purpose of this study was to document the subscapularis healing rate by use
      of postoperative ultrasound and correlate healing to physical examination
      findings. We included 23 patients (30 shoulders), who underwent total shoulder
      arthroplasty in the study. The evaluation included a standard history and
      physical examination, ultrasound evaluation, and outcome questionnaires. The
      postoperative examination included careful documentation of an abdominal
      compression test to evaluate subscapularis function. All patients had an
      improvement in functional outcome scores and shoulder range of motion. Of 30
      shoulders, 26 (87%) had an intact subscapularis as determined by ultrasound. By
      use of ultrasound as the gold standard, the abdominal-compression test had 7
      false-positive results, 3 false-negative results, 19 true-negative results, and 1
      true-positive result. The sensitivity of the abdominal-compression test was 25%,
      and the specificity was 73%. The negative predictive value was 86%, and the
      positive predictive value was 13%. The abdominal-compression test demonstrated a
      low sensitivity, specificity, and positive predictive value in this study for the
      assessment of subscapularis function after total shoulder arthroplasty. If a
      subscapularis tear is suspected in a patient after total shoulder arthroplasty,
      the abdominal-compression test is unreliable in predicting a subscapularis
      defect.

PMID- 16979048
TI  - The outcome of resection shoulder arthroplasty for recalcitrant shoulder
      infections.
AB  - Postarthroplasty infection is a devastating complication. In some patients,
      virulent pathogens or poor health complicate reconstruction. Resection
      arthroplasty is a viable option in such cases. Seven patients with resection
      arthroplasty following infection after shoulder arthroplasty were reviewed
      retrospectively at an average 20- month follow-up (range, 12-41). Average time
      between the initial procedure and the first debridement was 59.5 months (4-151
      months). The average number of debridements was 2.2 per patient (range, 1-4
      procedures). There were no complications, no recurrence of deep infection, no
      nerve damage, and no fractures. All patients were able to reach the opposite
      axilla, their backpocket and perineum, and their mouth. All but 1 patient were
      satisfied with their result. No patient had a satisfactory outcome via Neer's
      criteria. Resection arthroplasty is a reasonable salvage option for patients who
      are not good candidates for prosthetic reimplantation. This yields patients who
      can reliably perform basic activities of daily living.

PMID- 16979049
TI  - Magnetic resonance imaging and clinical findings before and after tendon
      transfers about the shoulder in children with residual brachial plexus birth
      palsy.
AB  - The purpose of this study was to assess the magnetic resonance imaging (MRI) and
      clinical outcome after tendon transfers about the shoulder in children with
      residual brachial plexus birth palsy. Twenty-three children with an average age
      at surgery of 5.3 +/- 1.7 years underwent transfer of the latissimus dorsi and
      teres major to the posterior rotator cuff with or without concomitant
      musculotendinous lengthenings. Preoperative MRI revealed glenoid retroversion
      measuring -25.3 +/- 14.3 degrees and only 29.5 +/- 15.5% percent of humeral head
      anterior to the middle of the glenoid. Clinical evaluation showed significant
      improvements in external rotation and abduction. Postoperative MRI 1 year after
      surgery revealed no change in glenoid retroversion (-24.5 +/- 14.2) or percent of
      humeral head anterior to the middle of the glenoid (28.4 +/- 14.9%). These
      results demonstrate that tendon transfers improve overall shoulder motion but do
      not reduce humeral head subluxation or enhance glenohumeral joint realignment.

PMID- 16979050
TI  - Interscalene regional anesthesia for arthroscopic shoulder surgery: a safe and
      effective technique.
AB  - There has been resistance to the use of interscalene regional block for
      arthroscopic shoulder surgery because of concerns about potential complications
      and failed blocks with the subsequent need for general anesthesia. The purpose of
      this study was to assess whether interscalene regional block is safe and
      effective and offers many advantages over general anesthesia for outpatient
      arthroscopic shoulder surgery. Through a retrospective chart review of
      consecutive arthroscopic shoulder surgeries over a 2.5-year time period, in a
      tertiary university medical center with an anesthesiology residency, 277
      interscalene blocks (96%) were successful; 12 (4%) required general anesthesia
      because of an inadequate block. There were no seizures, pneumothoraces, cardiac
      events, or other major complications. There was a 1% rate of minor complications,
      all of which were transient sensory neuropathies that resolved within 5 weeks on
      average. We conclude that interscalene block can provide effective anesthesia for
      arthroscopic shoulder surgery.

PMID- 16979052
TI  - Electromyographic analysis of physical examination tests for type II superior
      labrum anterior-posterior lesions.
AB  - Physical examination tests that place tension on the long head of the biceps may
      best reproduce symptoms in patients with type II superior labrum anterior
      posterior (SLAP) lesions. The objective of this study is to compare the
      normalized electromyographic signal of the long head of the biceps for SLAP
      lesion physical examination tests. The active compression test, anterior-superior
      SLAP test, biceps load test II, biceps tension test, and pain provocation test
      were performed on 13 subjects while biceps electromyographic data were recorded.
      The active compression test and biceps tension test had significantly higher
      electromyographic signals than the other tests. We found no significant
      differences when comparing forearm supination and pronation within individual
      tests. Because the active compression and biceps tension tests maximize muscle
      activation on the long head of the biceps, they may be the best physical
      examination tests by which to identify type II SLAP lesions.

PMID- 16979051
TI  - Why is the humeral retroversion of throwing athletes greater in dominant
      shoulders than in nondominant shoulders?
AB  - A rotation angle of the proximal humerus relative to the elbow (bicipital-forearm
      angle) was measured by use of ultrasonography to determine the relationship
      between humeral retroversion and growth in dominant and nondominant shoulders of
      66 elementary and junior high school baseball players. The subjects were aged 12
      years on average. The bicipital-forearm angle was significantly smaller in
      dominant shoulders than in nondominant shoulders. This indicated that the
      retroversion angle was greater in dominant shoulders than in nondominant
      shoulders. Furthermore, there was a moderately positive correlation between age
      and the bicipital-forearm angle in both dominant and nondominant shoulders. From
      these data, we conclude that the humeral retroversion angle decreases with age,
      and the decrease is much smaller in dominant shoulders. We assume that the
      repetitive throwing motion does not increase the retroversion of the humeral head
      but rather restricts the physiologic derotation process of the humeral head
      during growth.

PMID- 16979053
TI  - Magnetic resonance imaging accuracy for the diagnosis of superior labrum anterior
      posterior lesions in the community setting: eighty-three arthroscopically
      confirmed cases.
AB  - Magnetic resonance imaging (MRI) has been shown in the literature to have high
      accuracy for the diagnosis of superior labrum anterior-to-posterior (SLAP)
      lesions. However, these studies have been performed at specialized institutions
      and have not been evaluated for community settings. Our hypothesis was that MRI
      diagnosis of SLAP lesions in the community setting is not as accurate as
      suggested by previous literature. The MRI reports for 83 consecutive surgically
      confirmed type II SLAP lesions were evaluated. The findings regarding the
      presence of SLAP lesions were documented from the community radiologists' MRI
      readings. Two blinded, fellowship-trained musculoskeletal radiologists evaluated
      these same 83 MRIs, as well as 17 MRIs with surgically confirmed normal superior
      labra. The musculoskeletal radiologists also used a visual analog scale to
      subjectively grade the quality of each MRI. MRIs were performed at 14 different
      centers and were read by 28 different community radiologists. There were 37
      noncontrast MRIs and 46 MRI arthrograms. The community radiologists accurately
      identified 51% of the SLAP lesions. The sensitivities for the community
      radiologists were significantly better for the MRI arthrograms than for the
      noncontrast MRIs (P = .0002). For the two musculoskeletal radiologists, the
      sensitivities were 60% and 67.5%, and the specificities were 71% and 76.5%. The
      accuracies for the musculoskeletal radiologists were 62% and 69%. One of the
      musculoskeletal radiologists had significant correlation between the visual
      analog score and MRI diagnostic accuracy (P = .0006). The sensitivity for one of
      the musculoskeletal radiologists was significantly greater than the sensitivity
      for the community radiologists (P = .0063). The accuracies between the other
      musculoskeletal radiologist and the community radiologists were not significantly
      different (P = .0577). In this community setting, MRI was not accurate for the
      diagnosis of SLAP lesions. Musculoskeletal radiologists were more accurate than
      the community radiologists; however, the musculoskeletal radiologists were not as
      accurate as previous literature might predict.

PMID- 16979054
TI  - Clinical outcome of anterior shoulder instability with capsular midsubstance
      tear: a comparison of isolated midsubstance tear and midsubstance tear with
      Bankart lesion.
AB  - To analyze the clinical outcomes of patients with a midsubstance capsular tear
      for anterior shoulder instability, 21 shoulders with a midsubstance tear were
      reviewed. There were 7 isolated midsubstance tears (group I) and 14 combined
      midsubstance tears with Bankart lesions (group II). The Rowe score averaged 92.3
      points with 6 excellent and 1 good one in group I. Group II scored 86.3 points
      with 8 excellent, 3 good, 2 fair, and 1 poor (P = .184). The Rowe score averaged
      89.8 points for the cases with an arthroscopic procedure and 86.9 points with an
      open repair (P = .542). At the last follow-up, forward elevation increased by 6
      degrees in group I and 8 degrees in group II (P = .432). External rotation
      decreased by 8 degrees and 16 degrees , respectively (P = .150). The clinical
      outcomes of anterior instability with a midsubstance tear were good in both
      groups. The loss of external rotation was greater in the cases with combined
      midsubstance tears and Bankart lesions than in those with an isolated
      midsubstance tear.

PMID- 16979055
TI  - The association of subacromial dimples with recurrent posterior dislocation of
      the shoulder.
AB  - Posterior positional dislocation is a form of atraumatic posterior recurrent
      dislocation commonly presenting in late teenage years. It has been an observation
      of ours that patients with posterior positional dislocation may have a small skin
      dimple, or tether, over the posteromedial deltoid of both shoulders. Fourteen
      consecutive patients with an established diagnosis of recurrent posterior
      positional dislocation were taken from our diagnostic database and reviewed along
      with 14 age- and sex-matched controls. For each patient and control, a diagnostic
      battery of clinical signs of instability was recorded and a photograph taken of
      the posterior aspect of the shoulder. The posterior dimple sign was associated
      with posterior instability with a sensitivity of 67% and a specificity of 92%.
      The clinical association of a posterior skin dimple and posterior recurrent
      positional dislocation has not been recognized before. This feature is discussed
      and the literature is reviewed.

PMID- 16979056
TI  - Open intramedullary nailing with tension band and locking sutures for proximal
      humeral fracture: hot air balloon technique.
AB  - To reduce complications and increase fixation after the internal fixation of
      proximal humeral fractures, interlocking intramedullary nailing and tension-band
      and locking sutures were used simultaneously, and their results are reviewed.
      Twenty-six consecutive patients who underwent open intramedullary nailing with
      tension-band and locking sutures for proximal humeral fractures were selected.
      The mean follow-up period was 39 months. With regard to the functional
      evaluation, the mean Neer score was 90 points and the mean American Shoulder and
      Elbow Surgeons score was 85. When patients were divided into those aged less than
      65 years and those aged 65 years or greater and into those with 2-part fractures
      and those with 3-part fractures, postoperative pain, the American Shoulder and
      Elbow Surgeons score, and the Neer score showed no difference between the 2
      groups. Open intramedullary nailing accompanied by tension-band and locking
      sutures for proximal humeral fractures shows sufficient fixation in older
      patients, and therefore, good postoperative shoulder function can be expected.

PMID- 16979057
TI  - A clinically applicable fracture classification for distal humeral fractures.
AB  - The purpose of this study was to design a clinically applicable classification
      for distal humeral fractures that would provide guidance to the surgeon with
      regard to surgical approach and operative management. The new classification was
      assessed by use of the original radiographs from a study comparing distal humeral
      fracture classifications undertaken in Oxford, England, and was validated by use
      of the exact methodology of that study. Nine independent assessors were asked to
      classify 33 sets of radiographs on 2 separate occasions using the classifications
      of Riseborough and Radin, Mehne and Jupiter, and the AO, as well as the new
      classification system. With the use of the kappa statistic, the level of
      interobserver and intraobserver agreement was determined. The new classification
      system was found to be both substantially reliable (kappa, 0.664) and
      reproducible (kappa, 0.732). The new classification achieved superior
      interobserver and intraobserver agreement compared with the other 3
      classification systems, with a low proportion of unclassifiable fractures. Used
      in conjunction with a management algorithm, we believe that the new
      classification aids the surgical decision-making process for these complex
      fractures.

PMID- 16979058
TI  - Comparative study between minimal medial epicondylectomy and anterior
      subcutaneous transposition of the ulnar nerve for cubital tunnel syndrome.
AB  - The purpose of this study was to review the results of 2 surgical methods for
      treating cubital tunnel syndrome. From 1994 to 2001, minimal medial
      epicondylectomy was performed on 22 elbows, and anterior subcutaneous
      transposition of the ulnar nerve was done on 34 elbows. In the group treated by
      medial epicondylectomy, 9 of the results (41%) were excellent, 10 (45%) were
      good, 2 (9%) were fair, and 1 result (5%) was poor. In the group treated by
      anterior subcutaneous transposition of ulnar nerve, 14 of the results (41%) were
      excellent, 13 (38%) were good, 6 (18%) were fair, and 1 result (3%) was poor. No
      significant difference was found between the 2 groups (P < .05). Both methods can
      be used for the treatment of cubital tunnel syndrome with a high rate of
      satisfaction.

PMID- 16979059
TI  - Distal biceps tendon reconstruction in chronic ruptures.
AB  - The purpose of this retrospective study was to evaluate the results of anatomic
      reattachment with reconstruction of the distal biceps tendon using an Achilles
      tendon allograft in 7 male patients with chronic distal biceps ruptures. Through
      a 1-incision anterior approach, the tendon allograft was attached to the
      bicipital tuberosity by using suture anchors and then secured to the biceps
      remnant. Follow-up averaged 29 months. Mean elbow flexion was 145 degrees, an
      extension deficit of 20 degrees was observed in 1 patient, and mean
      pronosupination was 170 degrees. All patients had 5/5 strength in flexion and
      supination on manual testing, and all returned to their employment. Mean
      supination strength was 87% of the contralateral healthy extremity. Six achieved
      an excellent and 1 a good rating in the Mayo elbow performance score. No
      complications were encountered. This technique is an excellent alternative to
      nonanatomic reattachment to the brachialis muscle for patients with high
      functional demands in pronosupination.

PMID- 16979060
TI  - Proximal humeral fractures: regional differences in bone mineral density of the
      humeral head affect the fixation strength of cancellous screws.
AB  - The purpose of this study was to investigate the 3-dimensional trabecular bone
      mineral density (BMD) in the humeral head and determine the effects of trabecular
      BMD on the pullout strength of cancellous screws. Five regions of interest (ROIs)
      were defined in the humeral head (superior- anterior, superior-posterior,
      central, inferior-anterior, and inferior-posterior). The trabecular BMD of each
      ROI was determined by use of peripheral quantitative computed tomography.
      Cancellous screws were inserted in each ROI and cyclically loaded. The superior
      anterior ROI had a lower trabecular BMD than all other ROIs (P < .001). The
      central ROI had a higher trabecular BMD than the inferior-anterior ROI (P < .01),
      whereas no differences were found between the inferior-posterior, superior
      posterior, and central ROIs. Pullout strength was lower in the superior-anterior
      ROI compared with all other ROIs (P < .01). The trabecular BMD and pullout
      strength were significantly correlated (P < .01). Placement of screws in regions
      with a higher trabecular BMD may help to prevent implant loosening and may
      improve patient outcome.

PMID- 16979061
TI  - Effects of glenoid component version on humeral head displacement and joint
      reaction forces: an experimental study.
AB  - The purpose of this study was to determine whether changes in glenoid version are
      associated with humeral head displacement and changes in the joint reaction
      forces, as these might contribute to instability or loosening in total shoulder
      replacement. A total shoulder prosthesis was implanted in neutral version in 6
      cadaveric shoulders. Glenoid version was then changed in steps of 4 degrees
      toward more anteversion and retroversion. An increase in anteversion resulted in
      anterior translation of the humeral head and in eccentric loading of the anterior
      part of the glenoid. Retroversion was associated with posterior displacement and
      posterior loading of the glenoid. A change in rotation of the humeral component
      did not compensate for altered version of the glenoid component. These results
      suggest that both instability and glenoid component loosening may be related to
      the version of the glenoid component. Therefore, assessment of loosening and
      instability justifies precise assessment of glenoid component version.

PMID- 16979062
TI  - Comparison of ultrasonic suture welding and traditional knot tying in a rabbit
      rotator cuff repair model.
AB  - The purpose of this study is to evaluate ultrasonic suture welding of
      monofilament suture in an animal model of rotator cuff repair with biomechanical
      and histologic analyses. We randomly assigned 46 shoulders in 23 rabbits to 1 of
      3 treatment groups: sham-operated (n = 15), knotted (n = 15), and welded (n =
      16). Supraspinatus defects were surgically created and acutely repaired with
      suture anchors loaded with either No. 2-0 Ethibond for knotted group or No. 2-0
      nylon for welded shoulders. Eighteen weeks postoperatively, all animals were
      killed, and the shoulders underwent either biomechanical testing or histologic
      analysis. The maximum stress of the sham-operated group (20.6 N/mm2) was
      significantly greater than that of both the knotted (10.2 N/mm2) and welded (8.3
      N/mm2) groups (P < .05), but no differences were observed between the knotted and
      welded groups. Although some histologic changes were noted, none was considered
      to be significant to distinguish either group.

PMID- 16979063
TI  - Biomechanical evaluation of a rotator cuff defect model augmented with a
      bioresorbable scaffold in goats.
AB  - A bioresorbable patch used for augmentation of rotator cuff repair was evaluated
      to determine if it would increase strength of cuff repairs associated with tendon
      defects and also show histologic incorporation over time. Forty goats underwent
      rotator cuff repairs of the infraspinatus tendon bilaterally. Tendons were
      detached and a defect was created prior to repair. One side was repaired and
      augmented with a 4 cm2 polylactic acid patch in each animal. On the other side,
      the same size defect was repaired in the same manner but without the patch to
      serve as a control. Animals were sacrificed at 3, 6, 12, and 24 weeks. Ultimate
      load to failure and histology were reported. No significant difference in load to
      failure was found between groups. A cellular fibrous tissue occupied the patch at
      6 weeks, which over time matured into a dense, homogeneous fibrous tissue with
      alignment of collagen between the scaffold bundles.

PMID- 16979064
TI  - Scapular thickness--implications for fracture fixation.
AB  - The purpose of this study was to measure and map scapula osseous thickness to
      identify the optimal areas for internal fixation. Eighteen (9 pairs) scapulae
      from 2 female and 7 male cadavers were used. After harvest and removal of all
      soft tissues, standardized measurement lines were made based on anatomic
      landmarks. For consistency among scapulae, measurements were taken at standard
      percentage intervals along each line approximating the distance between two
      consecutive reconstruction plate screw holes. Two-mm-diameter drill holes were
      made at each point, and a standard depth gauge was used to measure thickness. The
      glenoid fossa (25 mm) displayed the greatest mean osseous thickness, followed by
      the lateral scapular border (9.7 mm), the scapula spine (8.3 mm), and the central
      portion of the body of the scapula (3.0 mm). To optimize screw purchase and
      internal fixation strength, the lateral border, the lateral aspect of the base of
      the scapula spine, and the scapula spine itself should be used for anatomic sites
      of internal fixation of scapula fractures.

PMID- 16979065
TI  - From the vulnerable plaque to the vulnerable patient: imaging and clinical
      implications.

PMID- 16979066
TI  - Carotid vulnerable lesions are related to accelerated recurrence for cerebral
      infarction magnetic resonance imaging study.
AB  - RATIONALE AND OBJECTIVES: We sought to test the hypothesis that magnetic
      resonance imaging (MRI)-defined vulnerable plaques correlate to accelerated
      reoccurrence of cerebrovascular events and to evaluate the potential use of MRI
      in secondary prevention of ischemic stroke. MATERIALS AND METHODS: Fifty-three
      symptomatic participants were recruited from patients sustaining their second MRI
      confirmed cerebral infarction. Nine participants were women and 44 were men; the
      mean age was 69.2 years (range, 55-94 years). Patients were imaged within 7 days
      after the reoccurrence of cerebral infarction. The MRI diagnostic signals defined
      a classification of lesion type. We compare the interval between two cerebral
      infarctions with plaque vulnerability defined by the MRI lesion type. We used a
      Cox proportional hazards model to calculate the relationship between vulnerable
      lesions and the interval of cerebral infarction, and we followed these patients
      for 180 days and compared the recurrent rate for the third-time cerebral
      infarction between patients with and without vulnerable plaque. RESULTS: The mean
      infarction recurrence interval for patients with vulnerable lesions was shorter
      than the mean interval for patients without vulnerable lesion (310.1 versus
      1697.2, P< .001). In patients with recurrent cerebral infarction within 1 year,
      vulnerable lesions were more frequently detected (76% versus 19%, P< .001). The
      patients with vulnerable lesions had an 8.8-fold higher hazard risk (8.8; P<
      .001, 95% confidence interval, 3.9-19.7) than those without vulnerable lesions
      after adjustment for risk factors. For those with vulnerable plaque, the
      morbidity of third-time cerebral infarction was higher than those without (24%
      versus 3%, P = .023). CONCLUSION: MRI-defined vulnerable lesions in carotid
      arteries are related to accelerated recurrent cerebral infarction and high
      recurrent rate. MRI demonstrates clinical value in the secondary prevention of
      cerebral infarction.

PMID- 16979067
TI  - Analysis of location specific observer performance data: validated extensions of
      the jackknife free-response (JAFROC) method.
AB  - RATIONALE AND OBJECTIVES: The free-response paradigm is being increasingly used
      in the assessment of medical imaging systems. The currently implemented method of
      analyzing the data, namely jackknife free-response (JAFROC) analysis, has some
      validation and applicability limitations. The purpose of this work is to address
      these limitations. MATERIALS AND METHODS: The general principles of modality
      evaluation and methodology validation are reviewed. A model for simulating free
      response data was used to test the statistical validity of several methods of
      analyzing the data. The methods differed only in the choice of the figure of
      merit used to quantify performance. Statistical validity was judged by
      investigating the behaviors of the methods under null hypothesis conditions of no
      difference between modalities. RESULTS: The validity of the different methods of
      analyzing the data was found to be dependent on the choice of figure of merit. A
      figure of merit is identified that accommodates abnormal images with multiple
      (one or more) lesions, detections of which could have different clinical
      significances (weights). This figure of merit is shown to be statistically valid.
      An extension of the analysis to single reader interpretations of images from
      different modalities is also shown to be statistically valid. CONCLUSION: With
      the validated enhancements, JAFROC is expected to be of greater utility to users
      of the free-response method. The extension to single-reader interpretations
      should be of particular value to developers of image processing algorithms,
      including developers of computer-aided diagnosis algorithms.

PMID- 16979068
TI  - Computer-aided detection of solid lung nodules in lossy compressed multidetector
      computed tomography chest exams.
AB  - RATIONALE AND OBJECTIVES: To assess the effect of three-dimensional (3D) lossy
      image compression of multidetector computed tomography chest scans on computer
      aided detection (CAD) of solid lung nodules greater than 4 mm in size. MATERIALS
      AND METHODS: A total of 120 cases, acquired with 1.25-mm collimation, were
      collected from 5 different sites, of which 66/120 were low-dose cases. Two chest
      radiologists established that 37 cases had no actionable lung nodules; the
      remaining 83 cases contained 169 nodules (range 3.8-35.0 mm, mean 5.8 mm +/- 3.0
      [SD]). All cases were compressed using the 3D Set Partitioning in Hierarchical
      Trees algorithm to 24:1, 48:1, and 96:1 levels. A study of the effect of
      compression on computer-aided detection (CAD) sensitivity was performed at
      operating points of 2.5 false marks (FM), 5 FM, and 10 FM per case using
      McNemar's test. Logistic regression models were used to evaluate the impact on
      CAD sensitivity by compression level on nodule and image characteristics.
      RESULTS: Compared with no compression, there was no significant degradation in
      CAD sensitivity found at any of the studied compression levels and operating
      points. However, between compression levels, there was marginal association with
      sensitivity. Specifically, 24:1 level was significantly better than 96:1 at all
      operating points, and occasionally better than no compression at 10 FM/case.
      Based on multivariate analysis, nodule location was found to be a significant
      predictor (P = .01) with a lower sensitivity associated with juxtapleural
      nodules. Nodule size, dose, reconstruction filter, and contrast medium were not
      significant predictors. CONCLUSION: CAD detection performance of solid lung
      nodules did not suffer until 48:1 compression.

PMID- 16979069
TI  - Validating volume flow measurements from a novel semiautomated four-dimensional
      Doppler ultrasound scanner.
AB  - RATIONALE AND OBJECTIVES: Accurate measurement of blood volume flow (in ml/min)
      is an important clinical goal. This project compared in vitro and in vivo volume
      flow measurements obtained with a novel, real-time three-dimensional (i.e., four
      dimensional) ultrasound scanner (Encore PV; Vuesonix Sensors, Wayne, PA) with
      those from an invasive transit time flowmeter. MATERIALS AND METHODS: A flow pump
      was used to generate pulsatile flow rates from 60 to 600 ml/min. The Encore
      detected absolute blood velocity vectors within a volume. The scanner determined
      the centerline of the vessel and volume flow was then automatically calculated.
      Results were compared with those of an invasive technique for volumetric blood
      flow measurements utilizing a transit-time flowmeter (TS420; Transonic Systems
      Inc., Ithaca, NY). In vivo, 10 second datasets of the volume flow in the distal
      aorta of six rabbits were obtained simultaneously with the Encore PV and the
      flowmeter. Data were compared using linear regression and Bland-Altman analysis
      (due to the lack of independence). RESULTS: In vitro, Encore and flowmeter
      measurements both matched the flow pump (r2 > 0.99; P < .0001) with mean errors
      of -11.8% and -0.3%, respectively. Marked underestimation of the true flow rates
      was encountered with the Encore at the lowest pump setting. In vivo mean volume
      flows between 10.6 and 79.3 ml/min were measured. Mean and maximum volume flows
      obtained with the two techniques correlated significantly (P < .0001) with r2
      values of 0.86 and 0.62, respectively. The corresponding root-mean-square errors
      were 6.9% for mean flow and 61.2% for maximum volume flow measurements.
      CONCLUSION: A new semiautomated four-dimensional Doppler device has been tested
      in vitro and in vivo. Mean volume flow measurements with this unit are comparable
      to those of an invasive flowmeter.

PMID- 16979070
TI  - Correlation of HER-2/neu overexpression with mammography and age distribution in
      primary breast carcinomas.
AB  - RATIONALE AND OBJECTIVES: HER-2/neu is a valuable prognostic and therapeutic
      marker in primary breast carcinoma. The objective of this study was to determine
      the mammographic and patient characteristics (age) that correlate with HER-2/neu
      overexpression in primary breast carcinoma. MATERIALS AND METHODS: HER-2/neu
      characteristics and preoperative mammograms were available in 498 patients with
      543 primary breast carcinomas (526 invasive carcinomas and 17 ductal carcinoma in
      situ). HER-2/neu status was determined by immunohistochemistry and fluorescence
      in situ hybridization. For evaluation of patient age distribution, age was
      divided into 5 groups. For mammography, breast composition and abnormal findings
      were categorized. Abnormal findings were divided into mass, calcification,
      architectural distortion, asymmetric density, or none. RESULTS: For age
      distribution, women under than 50 years had more frequent HER-2/neu
      overexpression than women aged 60-69 years (P < .05). On mammography, there was
      no significant correlation between breast composition and HER-2/neu status (P >
      .05). Calcifications were more significantly frequent in carcinomas with HER
      2/neu overexpression (56%) than in those without HER-2/neu overexpression (40%)
      (P = .001). Of the 242 carcinomas with calcifications on mammography, fine linear
      morphology was more significantly frequent in carcinomas with HER-2/neu
      overexpression (20%) when compared with those without HER-2/neu overexpression
      (10%) (P = .023). Diffuse distribution of calcifications was more common in
      carcinomas with HER-2/neu overexpression (11%) compared with carcinomas without
      HER-2/neu overexpression (5%) (P = .051). CONCLUSION: HER-2/neu overexpression in
      primary breast carcinoma is correlated with patients' age (under age 50) and
      calcifications at mammography.

PMID- 16979071
TI  - Computer-aided diagnosis scheme for identifying histological classification of
      clustered microcalcifications by use of follow-up magnification mammograms.
AB  - RATIONALE AND OBJECTIVES: Our purpose in this study was to investigate the
      usefulness of follow-up magnification mammograms (i.e., both current and previous
      magnification mammograms) in a computer-aided diagnosis (CAD) scheme for
      identifying the histological classification of clustered microcalcifications.
      MATERIALS AND METHODS: Our database consisted of current and previous
      magnification mammograms obtained from 93 patients before and after 3-month
      follow-up: 11 invasive carcinomas, 19 noninvasive carcinomas of the comedo type,
      25 noninvasive carcinomas of the noncomedo type, 23 mastopathies, and 15
      fibroadenomas. In our CAD scheme, we extracted five objective features of
      clustered microcalcifications from each of the current and previous magnification
      mammograms by taking into account image features that experienced radiologists
      commonly use to identify histological classifications. These features were then
      merged by a modified Bayes discriminant function for distinguishing among five
      histological classifications. For the input of the modified Bayes discriminant
      function, we used five objective features obtained from the previous
      magnification mammogram (previous features), five objective features obtained
      from the current magnification mammogram (current features), and the set of the
      five previous features and the five current features. RESULTS: The classification
      accuracies with the five current features were higher than those with the five
      previous features. These classification accuracies were improved substantially by
      using the set of the five previous features and the five current features. For
      the set of the five previous features and the five current features, the
      classification accuracies of our CAD scheme were 81.8% (9 of 11) for invasive
      carcinoma, 84.2% (16 of 19) for noninvasive carcinoma of the comedo type, 76.0%
      (19 of 25) for noninvasive carcinoma of the noncomedo type, 73.9% (17 of 23) for
      mastopathy, and 86.8% (13 of 15) for fibroadenoma. CONCLUSION: Our CAD scheme
      with use of follow-up magnification mammograms improved classification
      performance for mammographic clustered microcalcifications.

PMID- 16979072
TI  - The positive predictive value for diagnosis of breast cancer full-field digital
      mammography versus film-screen mammography in the diagnostic mammographic
      population.
AB  - RATIONALE AND OBJECTIVES: Diagnostic mammography is performed on women with
      clinical symptoms that suggest breast cancer or women for whom further
      mammographic evaluation has been requested because of an abnormal screening
      mammography. We assessed whether the use of full-field digital mammography would
      improve the positive predictive value (PPV) for the diagnosis of breast cancer in
      a diagnostic population compared with film-screen mammography. MATERIALS AND
      METHODS: From January 2002 to December 2003, 11,621 patients underwent diagnostic
      mammography at the University of North Carolina Hospital, Chapel Hill. Among
      these 11,621 patients, 1400 lesions in 1121 patients underwent biopsy. We
      included the biopsy-performed lesions, so PPV3 was used for comparison of PPVs
      between film-screen mammography and full-field digital mammography. Six breast
      radiologists interpreted the images using the Breast Imaging Reporting and Data
      System of the American College of Radiology. PPV3s were compared between film
      screen and full-field digital mammography in the entire study cohort and in
      specified subgroups according to different radiologists, breast density, and
      lesion type on mammography. The chi(2) and Fisher's exact tests were used for
      comparison of PPV3s between two modalities of mammography with the Bonferroni
      procedure for subgroup analysis. RESULTS: In the entire study cohort, PPV3s of
      full-field digital mammography and film-screen mammography were similar
      (difference in PPV3,-0.007; 95% confidence interval, -0.081 to 0.068; P = .8602).
      In predefined subgroups, there was no difference in PPV3 by the radiologist,
      breast density, or lesion type between two modalities of mammography (P > .005).
      CONCLUSION: There is no improvement in PPV for the diagnosis of breast cancer
      with full-field digital mammography compared with film-screen mammography in a
      large diagnostic population.

PMID- 16979073
TI  - Abdominal magnetic resonance imaging at 3.0 T what is the ultimate gain in signal
      to-noise ratio?
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to calculate the gain in
      signal-to-noise ratio (SNR) of four human abdominal tissues at 3.0 Tesla (T)
      compared with standard 1.5 T and to validate this calculation in vivo. MATERIALS
      AND METHODS: The expected gain in SNR at 3.0 T in the liver, pancreas, spleen,
      and kidney compared with standard 1.5 T was approximated theoretically for a T2
      weighted HASTE (half-Fourier acquisition single-shot turbo spin-echo) and a T1
      weighted gradient-echo in- and opposed-phase sequence. Fifteen healthy male
      subjects underwent abdominal MR imaging using a 1.5 T and 3.0 T scanner. Coronal
      T2-weighted HASTE images and axial T1-weighted gradient-echo in- and opposed
      phase images were acquired using the sequence parameters optimized by the vendor.
      RESULTS: Except for opposed-phased imaging of pancreatic tissue, in vivo adjusted
      SNR values of all abdominal tissues were significantly higher at 3.0 T for all
      sequences (P < .05). The highest overall gain in SNR was achieved with the HASTE
      sequence ranging from 3.8-fold for renal imaging to 7.4-fold for hepatic imaging.
      The theoretical calculation of SNR gain was in good agreement with the
      experimentally measured gain in SNR for the HASTE and the in-phase sequence.
      CONCLUSION: High-field abdominal MR imaging at 3.0 T offers significantly higher
      SNR compared with standard 1.5 T MR imaging.

PMID- 16979074
TI  - Mathematical modeling improves computed tomography diagnosis of traumatic aortic
      injury.
AB  - RATIONALE AND OBJECTIVES: Acute traumatic aorta injuries (ATAIs) following blunt
      thoracic trauma require rapid and accurate diagnosis for institution of
      lifesaving treatment. The use of computed tomography (CT) in the diagnosis of
      such injuries continues to improve and has the potential to become the diagnostic
      modality of choice in many trauma centers. A standardized diagnostic model may
      contribute to improvements in radiologist interpretation of CT for ATAIs.
      MATERIALS AND METHODS: The following diagnostic criteria were used to develop a
      diagnostic model for ATAIs: 11 areas of potential hematoma formation were
      identified in the mediastinum. Maximum short- and long-axis cross-sectional
      diameters of the aorta were measured. Qualitative morphologic information
      (contour change, intimal flap) was recorded. Smoothness of the aorta wall was
      assessed. These characteristics were quantified and analyzed for statistical
      significance, allowing for the development of an injury assessment model.
      RESULTS: The diagnostic model was used to score 69 blunt thoracic trauma patient
      cases. Average weighted kappa was 0.74, showing strong agreement among two
      observers and reproducibility of the model. The model improved injury assessment
      by classifying equivocal cases as either positive or negative. The ROC curve
      calculated from the original radiologist interpretation contained 86.1% area
      under the curve, while the curve for the new model contained 97.5%. The
      likelihood ratio increased from 30.06 to 48.67. The degree to which the new
      measure improved prediction over the original radiologist reading was tested
      using a nested model and yielded a reliable increment in model fit (chi2
      analysis: Deltachi2(3) = 20.929, P < or = .0001). Finally, beta weights
      calculated from each variable were used to create a quantitative best-fit
      diagnostic model for future use. CONCLUSION: We have developed a diagnostic tool
      that may help radiologists better evaluate CT for ATAIs.

PMID- 16979075
TI  - Evaluation of lung MDCT nodule annotation across radiologists and methods.
AB  - RATIONALE AND OBJECTIVES: Integral to the mission of the National Institutes of
      Health-sponsored Lung Imaging Database Consortium is the accurate definition of
      the spatial location of pulmonary nodules. Because the majority of small lung
      nodules are not resected, a reference standard from histopathology is generally
      unavailable. Thus assessing the source of variability in defining the spatial
      location of lung nodules by expert radiologists using different software tools as
      an alternative form of truth is necessary. MATERIALS AND METHODS: The relative
      differences in performance of six radiologists each applying three annotation
      methods to the task of defining the spatial extent of 23 different lung nodules
      were evaluated. The variability of radiologists' spatial definitions for a nodule
      was measured using both volumes and probability maps (p-map). Results were
      analyzed using a linear mixed-effects model that included nested random effects.
      RESULTS: Across the combination of all nodules, volume and p-map model parameters
      were found to be significant at P < .05 for all methods, all radiologists, and
      all second-order interactions except one. The radiologist and methods variables
      accounted for 15% and 3.5% of the total p-map variance, respectively, and 40.4%
      and 31.1% of the total volume variance, respectively. CONCLUSION: Radiologists
      represent the major source of variance as compared with drawing tools independent
      of drawing metric used. Although the random noise component is larger for the p
      map analysis than for volume estimation, the p-map analysis appears to have more
      power to detect differences in radiologist-method combinations. The standard
      deviation of the volume measurement task appears to be proportional to nodule
      volume.

PMID- 16979076
TI  - Gender differences in diagnostic radiologists' annual incomes.
AB  - RATIONALE AND OBJECTIVES: Specialty, work effort, and gender have been shown to
      be associated with physicians' annual incomes; however, careful examination of
      the association between provider gender and physician incomes after correcting
      for other factors likely to influence income has not been conducted at the
      subspecialty level. We sought to determine the association between provider
      gender and diagnostic radiologists' annual incomes after controlling for work
      effort, provider characteristics, and practice characteristics. MATERIALS AND
      METHODS: Using survey responses that were collected throughout the 1990s from 491
      actively practicing white diagnostic radiologists, we generated a linear
      regression model to determine the association between provider gender and
      radiologists' annual incomes after controlling for work effort, provider
      characteristics, and practice characteristics. RESULTS: White female radiologists
      reported working 2% fewer annual hours than their white male counterparts. Female
      radiologists had practiced medicine for fewer years than males, were more likely
      to be employees, as opposed to having an ownership interest in the practice, and
      were equally likely to be board certified. After adjustment for work effort,
      provider characteristics, and practice characteristics, female radiologists' mean
      annual income was $273,907, or $80,090 (23%) lower than that for white males (95%
      CI: $113,930 lower to $46,250 lower, P < .001). CONCLUSIONS: During the 1990s,
      female gender was associated with lower annual incomes among diagnostic
      radiologists. Researchers should further explore the relationship between
      physician gender and incomes to determine what factors might cause the
      differences that we found.

PMID- 16979077
TI  - Teaching radiology resident didactics using videoconferencing development of a
      videoconferencing network to increase the efficiency of radiology resident
      training.

PMID- 16979079
TI  - Left out.

PMID- 16979080
TI  - The history of history.

PMID- 16979082
TI  - Inter-disciplinary focus groups on telephone medicine: a quality improvement
      initiative.
AB  - OBJECTIVE: To identify opportunities for quality improvement in long-term care
      telephone medicine using a model of interdisciplinary focus groups. DESIGN:
      Descriptive pilot project. SETTING: Extended Care and Rehabilitation Center
      (ECRC), Durham VA Medical Center, Durham, North Carolina. PARTICIPANTS: Eight of
      20 registered or licensed practical nurses and 4 of 6 geriatric medicine fellows
      voluntarily participated in this quality improvement project. MEASUREMENTS: In
      two 45-minute focus groups, participants were asked to discuss 3 open-ended
      questions related to telephone medicine. Comments were recorded during the
      discussions; topical themes were identified by the authors. RESULTS: Participant
      comments could be categorized into 4 domains describing the characteristics of
      nurses and physicians who practice the best telephone medicine: (1) provides the
      appropriate medical component of patient care; (2) appreciates contextual issues;
      (3) respects the other party's time and resources; and (4) possesses a
      collaborative attitude. The focus groups identified 5 quality improvement goals:
      (1) better nursing assessment and provision of patient information; (2)
      minimization of non-urgent calls after hours; (3) more decisive physician action
      (or explanation of inaction); (4) better physician familiarity with facility
      policies/logistics; and (5) better communication/paging system. The discussion
      format allowed nurses and physicians to identify and respond to potential
      barriers to improving quality in each area. CONCLUSION: Nurses and physicians
      appreciate unique aspects of long-term care telephone medicine and identify
      distinct barriers to improving practice. Interdisciplinary focus groups were a
      productive step toward understanding the telephone medicine experience in our
      facility and developing quality improvement interventions for both nurses and
      physicians.

PMID- 16979083
TI  - Reliability of a structured assessment for nonclinicians to detect delirium among
      new admissions to postacute care.
AB  - OBJECTIVE: To evaluate the interrater reliability of a structured delirium
      assessment method for nonclinician interviewers in elderly patients newly
      admitted for postacute care. DESIGN: Prospective assessment using dyads of
      nonclinician raters. SETTING: Postacute (Medicare) units at 6 skilled nursing
      facilities. PARTICIPANTS: Forty elderly patients newly admitted for postacute
      care from medical or surgical units at acute care hospitals. MEASUREMENTS:
      Subjects underwent dual delirium assessments within 5 days of admission. The
      standardized delirium assessment included the Mini-Mental Status Exam and Digit
      Span to assess overall cognitive function, the Delirium Symptom Interview to
      elicit specific delirium symptoms, the Memorial Delirium Assessment Scale to
      measure the severity of delirium, and the Confusion Assessment Method (CAM) to
      make the diagnosis of delirium. A coding protocol that linked observations to
      specific coding was used to improve reliability. RESULTS: The structured delirium
      assessment process produced very high interobserver agreement for all
      instruments. Kappa for agreement on delirium diagnosis was 0.95. CONCLUSIONS:
      Nonclinician interviewers using a structured delirium assessment achieved
      reliability that rivaled or exceeded that of trained clinical assessors in other
      studies. Nonclinicians may offer an effective alternative for the assessment of
      delirium among postacute patients in skilled nursing facilities.

PMID- 16979084
TI  - Interobserver reliability of radiologists' interpretations of mobile chest
      radiographs for nursing home-acquired pneumonia.
AB  - OBJECTIVES: To determine the interobserver reliability of radiologists'
      interpretations of mobile chest radiographs for nursing home-acquired pneumonia.
      DESIGN: A cross-sectional reliability study. SETTING: Nursing homes and an acute
      care hospital. PARTICIPANTS: Four radiologists reviewed 40 mobile chest
      radiographs obtained from residents of nursing homes who met a clinical
      definition of lower respiratory tract infections. MEASUREMENTS: Radiologists were
      asked to interpret radiographs with respect to the film quality; presence,
      pattern, and extent of an infiltrate; and the presence of a pleural effusion or
      adenopathy. Interrater reliability was evaluated using the intraclass correlation
      coefficient derived from a 2-way random effects model. RESULTS: On average the
      radiologists reported that 6 of the 40 films were of very good or excellent
      quality and 16 of the 40 were of fair or poor quality. When the finding of an
      infiltrate was dichotomized (0 = no; 1 = possible, probable, or definite) all 4
      radiologists agreed on 21 of the 37 chest radiographs. The intraclass correlation
      coefficient for the presence or absence of infiltrates was 0.54 (95% confidence
      intervals [CI] 0.38 to 0.69). For the 14 radiographs where infiltrates were
      observed by all radiologists, intraclass correlation coefficients for the
      presence of pleural effusions was 0.08 (95% CI -0.10 to 0.41), hilar adenopathy
      0.54 (95% CI 0.29 to 0.79), and mediastinal adenopathy 0.49 (95% CI 0.21 to
      0.76). CONCLUSION: In conclusion, the interrater agreement among radiologists for
      mobile chest radiographs in establishing the presence or absence of an infiltrate
      can be judged to be "fair." Treatment decisions need to include clinical findings
      and should not be made based on radiographic findings alone.

PMID- 16979085
TI  - Using a modified nominal group technique to elicit director of nursing input for
      an osteoporosis intervention.
AB  - BACKGROUND: Barriers prevent osteoporosis care in nursing homes. Successful
      interventions designed to circumvent these barriers benefit from target recipient
      input during development. OBJECTIVE: To elicit suggestions for an osteoporosis
      quality improvement intervention designed for use by nursing home health care
      professionals. DESIGN: Modified nominal group technique. SETTING: Convenience
      sample of Alabama nursing home directors. PARTICIPANTS: Fifteen Alabama nursing
      home directors of nursing were recruited by mailing. Sixty percent of respondents
      participated (n = 9). MEASUREMENTS: In the first phase conducted via
      teleconference, an experienced moderator used a preformulated question and
      elicited 41 suggestions to improve osteoporosis care in nursing homes.
      Substantively similar suggestions were combined and idiosyncratic suggestions
      were discarded resulting in the retention of 20 suggestions. In the second phase
      conducted by mail, the same participants rated the 20 suggestions based on
      perceived practicality and helpfulness. Elements were grouped into tertiles based
      on the ranking of the mean ratings of the 2 attributes and then cross-tabulated.
      RESULTS: All director of nursing (n = 9) participants completed both phases. The
      most practical, most helpful suggestions were information on fall prevention
      program implementation, osteoporosis treatment protocols, and osteoporosis
      medication information. CONCLUSIONS: A modified nominal group technique provided
      useful information from nursing home directors of nursing for an osteoporosis
      intervention. The technique proved efficient and facile to perform.

PMID- 16979086
TI  - Effects of continuous activity programming on behavioral symptoms of dementia.
AB  - OBJECTIVES: To describe the effect of continuous activity programming on
      behavioral symptoms of dementia. DESIGN: Observational study based on quality
      improvement data. SETTING: Two Dementia Special Care Units in different
      locations. PARTICIPANTS: Ninety veterans with dementia provided with long-tem
      care. INTERVENTION: Continuous activity programming. MEASUREMENTS: Data were
      extracted from the MDS files and obtained by questionnaires filled out by staff
      members not involved in activity programming. RESULTS: Two settings of continuous
      activity programming, requiring no additional staffing, resulted in increased
      number of hours residents were involved in activities, decreased use of
      psychotropic medications, improved nutrition, and increased family satisfaction
      without additional staff. When additional staff was available, more intensive
      continuous activity programming further decreased agitation and improved sleep.
      CONCLUSION: Continuous activity programming may be instituted without staffing
      change but the benefit is increased if additional staffing is available.

PMID- 16979087
TI  - Finding the person behind the pain: chronic pain management in a patient with
      traumatic brain injury.
AB  - Chronic pain is common after a traumatic brain injury. Cognitive impairment post
      injury may be a consequence of the brain injury alone, or in combination with
      pain, clinical depression, and psychological and emotional factors. We present a
      case of a severely cognitively impaired person post-traumatic brain injury, whose
      behavior included social withdrawal, irritability, and agitation around direct
      care--which was unresponsive to psychotropic intervention or care delivery
      strategies. The introduction of an opioid made a significant improvement in the
      cognition and quality of life of the individual. This case suggests that
      clinicians should consider a trial of opioid analgesics in individuals with brain
      injury who have significant cognitive impairment in association with other
      behaviors suggestive of depression and pain.

PMID- 16979088
TI  - To treat or not to treat, that is the question: proceedings of the Quebec
      Symposium for the Treatment of Osteoporosis in Long-term Care Institutions, Saint
      Hyacinthe, Quebec, November 5, 2004.
AB  - OBJECTIVES: Patients in long-term care institutions (LTCI) are especially at risk
      for osteoporotic fractures owing to their lack of mobility, poor nutrition, and
      limited sun exposure. Previous reports have shown that osteoporosis is
      underdiagnosed and undertreated in LTCI despite the high incidence of
      osteoporotic fractures in these settings. This document has been developed to
      assist clinicians practicing in LTCI with the diagnosis and treatment of
      osteoporosis in their institutionalized patients. These proceedings offer an
      overview of the particular characteristics of patients at LTCI. Management
      strategies include both nonpharmacological and pharmacological interventions for
      the prevention and treatment of osteoporotic fractures in very frail older
      subjects. PARTICIPANTS: This guide is an edited review of presentations and
      discussions held by specialists in osteoporosis in the elderly together with
      physicians and pharmacists practicing in LTCI in the province of Quebec. This
      symposium was held in Saint-Hyacinthe, Quebec on November 5, 2004. VALUES: The
      value of a given diagnostic test or treatment option was determined based on the
      clinical experiences and opinions of the participants and a review of the
      literature from an evidence-based perspective. RECOMMENDATIONS: All patients
      located at LTCI are at potential risk for osteoporotic fractures. Global
      interventions should include vitamin D, calcium, and a comprehensive exercise
      program. In patients who are at high risk for osteoporotic fractures or with
      previous fractures, pharmacological treatment should be started. VALIDATION:
      These recommendations were approved during the final plenary of the symposium.
      All the prevailing opinions were summarized and included in this article.

PMID- 16979089
TI  - Sexual abuse of vulnerable adults: the medical director's response.

PMID- 16979090
TI  - Harmless herbs? Think again: merits of a complete medication history.

PMID- 16979091
TI  - Identification and management of depression in nursing facility residents.

PMID- 16979092
TI  - Day care for demented elderly in a dairy farm setting: positive first
      impressions.
AB  - OBJECTIVE: Long-term care for demented patients in the Netherlands is changing.
      The focus is now more on quality of life and delaying institutionalization by
      offering substitutes to the traditional nursing home. In this article, we present
      a new type of day care, offered on a small dairy farm setting. DESIGN: A small
      observational study was performed to get a first impression of the effects of
      care farm day care on demented patients. Also, global comparisons were made
      between patients attending day care in the farm setting and patients attending
      regular day care in a nursing home. RESULTS: Demented patients attending day care
      on the farm showed fewer behavioral problems, used, on average, fewer drugs,
      including psychotropic drugs, and were more actively involved in normal daily
      activities. Moreover, family caregivers were more satisfied with this new type of
      day care. CONCLUSION: Currently, there is only a scant amount of information to
      support the therapeutic effects of day care in farm settings. This experience
      indicates a positive trend of this new form of day care. Well-designed
      longitudinal follow-up studies are needed to provide more substantial evidence of
      positive patient outcomes in this new care setting.

PMID- 16979093
TI  - Physician involvement in long-term care: bridging the medical and social models.

PMID- 16979094
TI  - Inter-observer reliability of radiologists' interpretation of mobile chest
      radiographs for nursing home-acquired pneumonia.

PMID- 16979095
TI  - Poor effect of family practice physician training at the organizational level in
      long-term care facilities in Flanders, Belgium.

PMID- 16979096
TI  - Cookbook medicine: recipe for disaster?

PMID- 16979098
TI  - Pediatric guidelines.

PMID- 16979099
TI  - Science and medicine.

PMID- 16979100
TI  - Institute for alternative futures seeks input.

PMID- 16979097
TI  - Listerine's long shadow: disease mongering and the selling of sickness.

PMID- 16979101
TI  - Trends that will affect your future ... A soldier in the sensoid wars.

PMID- 16979102
TI  - Why publish the Olive Leaf Report?

PMID- 16979103
TI  - Findings of and treatment for high levels of mercury and lead toxicity in ground
      zero rescue and recovery workers and lower Manhattan residents.
AB  - In 2005, the Olive Leaf Wholeness Center conducted a demonstration project that
      provided health assessment, testing, and treatment to 160 uniformed service
      personnel and residents of Lower Manhattan who were exposed to the air at Ground
      Zero following September 11, 2001, for extended periods of time. The program,
      known as Project Olive ReLeaf, found that most individuals had eight or more
      serious health complaints, including severe respiratory problems, digestive
      problems, skin rashes, sleeplessness, anxiety, depression, weight gains, elevated
      blood pressure, lethargy, and recurrent headaches. Heavy metal toxicity was
      suspected as a causal factor for many of these symptoms. Of those tested for
      heavy metal toxicity, using a challenge urine test, 85% had excessively high
      levels of lead and mercury. Chelation treatment using dimercaptuosuccinic acid
      (DMSA), a Food and Drug Administration (FDA)-approved sulfur compound, was the
      primary treatment prescribed. After three to four months of treatment, the first
      cohort of 100 individuals reported significant (greater than 60%) improvement in
      all symptoms. (This demonstration program was developed based on the results of
      an earlier pilot in 2003 for 25 emergency service officers of the New York City
      Police Department.) In addition, adjunctive therapies to assist with the
      detoxification process and build the immune system were offered. A small grant
      has been received to conduct follow-up tests on a sample of those treated with
      DMSA.

PMID- 16979104
TI  - Double-blind test of the effects of distant intention on water crystal formation.
AB  - The hypothesis that water "treated" with intention can affect ice crystals formed
      from that water was pilot tested under double-blind conditions. A group of
      approximately 2,000 people in Tokyo focused positive intentions toward water
      samples located inside an electromagnetically shielded room in California. That
      group was unaware of similar water samples set aside in a different location as
      controls. Ice crystals formed from both sets of water samples were blindly
      identified and photographed by an analyst, and the resulting images were blindly
      assessed for aesthetic appeal by 100 independent judges. Results indicated that
      crystals from the treated water were given higher scores for aesthetic appeal
      than those from the control water (P = .001, one-tailed), lending support to the
      hypothesis.

PMID- 16979105
TI  - Meta-analysis of acustimulation effects on nausea and vomiting in pregnant women.
AB  - OBJECTIVE: We used meta-analysis to examine the effects of acustimulation (AS) on
      the prevention of nausea and vomiting in pregnant women (NVP). METHODS: Meta
      analysis of effects of acustimulations (ie, acupressure, acupuncture, and
      electrical stimulation [ETS]) on NVP was conducted. Fourteen trials, eight random
      controlled trials (RCTs), with one RCT having two treatment modalities with four
      groups, and six crossover controlled trials (N = 1655) published over the last 16
      years were evaluated for quality according to the Quality of Reports of Meta
      analysis of Randomized Controlled Trials (QUORUM) guidelines. Relative risks (RR)
      and 95% confidence intervals (CI) were calculated from the data provided by the
      investigators of the original trials. RESULTS: Before the treatment, 100% of the
      women (13 trials, n = 1615 women) were nauseated, but and 96.6% (1599/1655)
      reported vomiting. After the treatment, compared with the controls, AS (all
      modalities combined) reduced the proportion of nausea (RR = 0.47, 95% CI: 0.35
      0.62, P < .0001) and vomiting (RR = 0.59, 95% CI: 0.51-0.68, P < .0001).
      Acupressure methods applied by finger pressure or wristband reduced NVP. The ETS
      method was also effective in reducing NVP. However, the acupuncture method did
      not show effects on reducing NVP. There was a placebo effect when compared with
      controls in reducing nausea (three trials, RR = 0.63, 95% CI: 0.39-1.02, P =
      .0479) and vomiting (five trials, RR = 0.67, 95% CI: 0.50-0.91, P = .0084).
      CONCLUSIONS: This meta-analysis demonstrates that acupressure and ETS had greater
      impact than the acupuncture methods in the treatment of NVP. However, the number
      of acupuncture trials was limited for pregnant women, perhaps because it is
      impossible to self-administer the acupuncture and thus inconvenient for women
      experiencing NVP as chronic symptoms.

PMID- 16979106
TI  - The experience of transcendental meditation in middle school students: a
      qualitative report.
AB  - BACKGROUND: Transcendental Meditation (TM), a sitting meditation technique
      designed to quiet the mind and induce physical and mental relaxation, has been
      widely studied in adults. OBJECTIVE: Our objective was to explore systematically
      the first-person experience of young adolescents who practice TM. DESIGN: A
      descriptive, qualitative study using semistructured interviews. SETTING: Middle
      school setting. PARTICIPANTS: Participants included 10 seventh grade students who
      have practiced TM for a one-year period of time. RESULTS: Themes described by
      students resulting from meditation included the following: (1) an increasing
      state of restful alertness; (2) improvement in skills indicative of emotional
      intelligence (self-control, self-reflection/awareness, and flexibility in
      emotional response); and (3) improvement in academic performance. The state of
      restful alertness induced by meditation appeared central to facilitating growth
      in social-emotional capacities, academic performance, and flexibility in
      emotional response. The inner state of restful alertness provided students with
      greater capacity to expand their ways of looking inwardly at themselves and their
      relationships with others (emotional intelligence) as well as focusing their
      attention on controlling their behavior and keeping on task in school.
      CONCLUSIONS: Students described beneficial effects of TM: an increased state of
      restful alertness and greater capacity for self-reflection, self-control, and
      flexibility as well as improved academic performance. The state of restful
      alertness induced by meditation may facilitate the growth of social-emotional
      capacities necessary for regulating the emotional labiality and interpersonal
      stress of adolescence. Future empirical validation is needed to analyze
      systematically the impact of this practice on students' social-emotional and
      cognitive development and to determine whether its practice can serve as a
      protective function for helping students successfully meet the challenges of
      adolescence.

PMID- 16979107
TI  - Development and preliminary results of a self-administered intervention for
      individuals with fibromyalgia syndrome: a multiple case control report.

PMID- 16979108
TI  - An emerging paradigm: chemical exposures and health. Interview by Bonnie J.
      Horrigan.

PMID- 16979109
TI  - Chronobiology: it's about time.

PMID- 16979110
TI  - A reason to season: the therapeutic benefits of spices and culinary herbs.

PMID- 16979111
TI  - Learning from organic agriculture.

PMID- 16979112
TI  - The temple vision in palliative care.
AB  - Music-thanatology draws as much historical inspiration from the Asclepian ideal
      as it does from the practice of Cluniac monastic medicine. In both traditions,
      the patient initiates the social drama and is a most active agent in the healing
      process. In both traditions, the patient has the central voice and is listened to
      and responded to by the caregivers and clinicians, who facilitate and support in
      the spirit of service rather than direct/control. In both traditions, we may find
      death-bed healing without curing and be struck by the urgent, transcendental role
      of Beauty, as expressed in nature (human and elemental), the arts, architecture,
      and music. Clearly, our guest author envisions a profound end-of-life music
      thanatology clinical practice in which the well-known, empirical Hippocratic and
      the lesser known, sacred Asclepian are integrated into the ideals of monastic
      medicine. In so doing, not only are pain and suffering uniquely met, but a
      blessed, peace-filled or conscious transitus may occur, and each death-bed
      setting has the potential to become nothing less than a sanctuary for completion.

PMID- 16979113
TI  - Integrative pediatrics: past, present, and future.

PMID- 16979114
TI  - Innovations in integrative healthcare education: consortium expands with the
      addition of the University of Wisconsin and the Mayo Medical Center.

PMID- 16979115
TI  - Ask the experts.

PMID- 16979117
TI  - Macrophage activation by polysaccharide biological response modifier isolated
      from Aloe vera L. var. chinensis (Haw.) Berg.
AB  - A mannose-rich polysaccharide biological response modifier (BRM), derived from
      Aloe vera L. var. chinensis (Haw.) Berg., was demonstrated to be a potent murine
      B- and T-cell stimulator in our previous study. We here report the stimulatory
      activity of PAC-I on murine peritoneal macrophage. The polysaccharide when
      injected into mice enhanced the migration of macrophages to the peritoneal
      cavity. Peritoneal macrophage when treated by PAC-I in vitro had increased
      expression of MHC-II and FcgammaR, and enhanced endocytosis, phagocytosis, nitric
      oxide production, TNF-alpha secretion and tumor cell cytotoxicity. The
      administration of PAC-I into allogeneic ICR mice stimulated systemic TNF-alpha
      production in a dose-dependent manner and prolonged the survival of tumor-bearing
      mice. PAC-I is thus a potent stimulator of murine macrophage and the in vitro
      observed tumoricidal properties of activated macrophage might account for the in
      vivo antitumor properties of PAC-I. Our research findings may have therapeutic
      implications in tumor immunotherapy.

PMID- 16979118
TI  - Immunomodulating effects of lichen-derived polysaccharides on monocyte-derived
      dendritic cells.
AB  - Many naturally occurring polysaccharides from fungi and lichens have been found
      to have immunomodulating activity. However, the majority of these studies have
      focused on their effects on the innate arm of the immune system. Although
      dendritic cells (DCs) belong to the innate immune system, they play an important
      role as a bridge between the innate and the adaptive immune response. In this
      study, the effects of 11 chromatographically purified and well-characterised
      lichen polysaccharides (of different structural types) on the maturation of DCs
      were tested by analysing the secretion of IL-12p40 and IL-10 by human monocyte
      derived dendritic cells in vitro. Four of the polysaccharides upregulated IL-10
      secretion by the dendritic cells, as compared with unstimulated cells, the beta
      glucans lichenan and Ths-2 and the heteroglycans Pc-4 and thamnolan. IL-12p40
      secretion was significantly upregulated by the beta-glucan lichenan and the
      heteroglycans Pc-2, Pc-4, thamnolan and Ths-4, while the mature dendritic cells
      stimulated with the heteroglycan Pc-1 secreted significantly less IL-12p40 than
      the unstimulated cells. Proportional index (PI) was used to determine the
      relationship between the IL-12p40 and IL-10 secretion. The PI of all the beta
      glucans, i.e. lichenan, pustulan and Ths-2, and the heteroglycan thamnolan was
      significantly lower than the PI observed for the unstimulated cells, which was
      mainly due to increased IL-10 secretion. Therefore, these polysaccharides could
      be considered suitable candidates in tolerance and anti-inflammatory studies, as
      IL-10 is one of the major cytokines involved in tolerance and anti-inflammatory
      responses.

PMID- 16979119
TI  - Inhibition of IL-8 release from CFTR-deficient lung epithelial cells following
      pre-treatment with fenretinide.
AB  - Cystic fibrosis (CF) is characterized by a biochemical abnormality in the cystic
      fibrosis transmembrane conductance regulator (CFTR) channel. CFTR-deficient lung
      epithelial cells may have high constitutive glutathione (GSH) levels that could
      decrease the intracellular content of the sphingolipid second messenger,
      ceramide. Altered ceramide levels in CF cells could, in turn, lead to their
      resistance to apoptosis and an immune hyper-responsiveness. As fenretinide is a
      ceramide up-regulating drug that inhibits the activation of the pro-inflammatory
      transcriptional factor, nuclear factor (NF)-kappaB, the impact of fenretinide on
      unstimulated and tumor necrosis factor (TNF)-alpha stimulated production of NF
      kappaB-dependent interleukin (IL)-8 was studied in immortalized wild-type (non
      CF; 9HTEo-) and mutant DeltaF508 CFTR (CF; CFTE29o-) tracheal epithelial cells.
      Despite higher constitutive levels of GSH in CF cells, their intracellular
      ceramide content showed a greater enhancement following fenretinide and TNF-alpha
      treatment than non-CF cells. Clinically relevant concentrations of fenretinide
      (1.25, 2.5 and 5 microM) inhibited TNF-alpha-induced IL-8 production of CF cells
      by up to 73% but had no effect or increased the IL-8 production in non-CF cells.
      Although fenretinide treatment was associated with a higher intracellular
      ceramide content in the mutant DeltaF508 CFTR cells, the fenretinide-mediated
      decrease in IL-8 secretion was not consistently explained by changes in the
      intracellular content of this sphingolipid. Fenretinide was ineffective in
      increasing the susceptibility to apoptosis in CF cells whereas non-CF cells were
      sensitive to the apoptosis induced by both fenretinide and cisplatin exposure.
      The fenretinide mediated decrease in IL-8 release in CF cells under TNF-alpha
      stimulated conditions presents the possibility that the lung inflammation in CF
      could be attenuated via low dose fenretinide treatment.

PMID- 16979120
TI  - Changes in maternal and fetal nicotine distribution after maternal administration
      of monoclonal nicotine-specific antibody to rats.
AB  - Vaccination against nicotine to elicit the production of nicotine-specific
      antibodies is a potential treatment for tobacco addiction which reduces nicotine
      distribution from serum to brain. Vaccination of pregnant rats also reduces the
      distribution of maternally-administered nicotine to the fetal brain. Whether this
      is due to maternal antibody reducing the transfer of nicotine from mother to
      fetus, or to fetal antibody altering the distribution of nicotine within the
      fetus, is not clear. In the current study, passive immunization of rats with the
      murine monoclonal nicotine-specific antibody Nic311 was used as a surrogate for
      vaccination because antibody transfer to the fetus was anticipated to be lower
      than with vaccination. Pregnant rats received nicotine from gestational day (GD)
      18-20 as frequent i.v. boluses to simulate nicotine exposure from smoking. Nic311
      was administered at doses of 30, 80 or 240 mg/kg on GD 19. Fetal serum Nic311
      levels on GD 20 were <3% of concurrent maternal levels, but concentrations of up
      to 20 ug/ml in fetal serum were obtained owing to the very high levels in
      maternal serum. Accumulation of the chronically administered nicotine, measured
      on GD 20, was not changed by Nic311 treatment in either maternal or fetal brain.
      The early distribution of nicotine to maternal brain, measured 5 min after a
      dose, was markedly reduced by Nic311, while the early distribution of nicotine to
      whole fetus and fetal brain was not substantially altered. These data suggest
      that the limited transfer of Nic311 to the fetus in turn limits the ability of
      Nic311 to reduce nicotine distribution to the fetal brain.

PMID- 16979121
TI  - Histone deacetylase inhibitors induce antigen specific anergy in lymphocytes: a
      comparative study.
AB  - Induction of immune tolerance to transplanted tissue continues to be a challenge
      for organ transplantation. In the present study, six widely used histone
      deacetylase inhibitors (HDAI), sodium butyrate (n-butyrate), Trichostatin A,
      Oxamflatin, Scriptaid, HDAC I and HDAC III, were examined for ability to induce
      antigen-specific immune anergy in cloned and naive murine CD4(+) T cells. When
      first compared for their ability to inhibit histone deacetylation Trichostatin A
      was found to be 10 times more potent than HDAC III, Oxamflatin and Scriptaid and
      10(4) times more potent than n-butyrate. When we compared ability to inhibit
      CD4(+) T cell proliferation in response to IL-2 stimulation, Trichostatin A was
      the most potent with 100% inhibition using 100 nM Trichostatin A, while 1 muM of
      HDAC III, Oxamflatin and Scriptaid and 1 mM of n-butyrate were required for this
      effect. When the tolerogenic activity of Trichostatin A, Scriptaid and n-butyrate
      were compared using cloned Th1 cells specific for keyhole limpet hemocyanin
      (KLH), all three HDAI were effective, but Trichostatin A was again the most
      potent. Finally, Trichostatin A (0.05 mM) was shown to induce anergy in OT-II
      ovalbumin-specific naive CD4(+) T-cells. We concluded that Trichostatin A was the
      most potent HDAI with regard to inhibition of histone deacetylation and the
      ability to induce antigen-specific anergy in both cloned and naive CD4(+) T
      cells. These results will guide future studies examining HDAIs for ability to
      induce clinical tolerance in organ transplantation.

PMID- 16979122
TI  - Influence of leflunomide on gastrointestinal Candida albicans infection induced
      in naive and arthritic newborn mice.
AB  - Mucosal Candida albicans infection in immunocompromised individuals being treated
      with recently advanced drugs can progress to systemic disease. One such
      medication applied in patients with rheumatoid arthritis is leflunomide. The
      object of the present study was to investigate the effect of leflunomide on a
      model of gastrointestinal (g.i.) C. albicans infection induced in naive or
      arthritic mice and on the host resistance to systemic re-infection. Newborn mice
      were orally inoculated with 1 x 10(5) colony forming units (CFU) of C. albicans
      and at age of 5 weeks they were treated with 5 mg/kg or 20 mg/kg of leflunomide
      for 10 consecutive days. Both doses elevated the yeast colonization of the
      stomach, without the dissemination into the internal organs. This was in parallel
      with the enhanced delayed type hypersensitivity (DTH) reaction to the yeast.
      Contrary to that, leflunomide caused a shift to Th2 reactivity by prevalence of
      IL-4 to IFN-gamma and a suppression of anti-Candida antibody synthesis by a
      higher dose. It might be supposed that infection increased autoimmune response in
      arthritic mice, according to stimulated DTH reaction to collagen. The
      administration of leflunomide during the simultaneous development of infection
      and arthritis diminished anti-Candida and anti-collagen antibody synthesis
      compared to untreated infected arthritic mice. The improved survival of arthritic
      infected animals against severe systemic re-infection was not changed after
      administration of leflunomide to re-infected arthritic mice. We can conclude that
      although leflunomide influenced cytokine secretion and suppressed anti-Candida
      antibody production it neither provokes a progression from gastrointestinal to
      systemic C. albicans infection nor increases the susceptibility to severe C.
      albicans re-infection of arthritic mice.

PMID- 16979123
TI  - Protective role of wogonin against lipopolysaccharide-induced angiogenesis via
      VEGFR-2, not VEGFR-1.
AB  - Wogonin, one of flavonoid derived from particular plants, enriches the property
      of anti-inflammation. Inflammation-stimulated angiogenesis plays an important
      role in many pathological diseases, such as rheumatoid arthritis,
      atherosclerosis, and cancer. The aim of this study was to investigate the
      suppressive effect of wogonin on lipopolysaccharide (LPS)-induced angiogenesis in
      human umbilical endothelial cell (HUVEC) cultures. By cell differentiation
      assays, migration and tube formation activity under LPS treatment were evaluated.
      Besides, IL-6 neutralizing antibody was added to test the inhibitory effect in
      the phenotypic alteration. Western blot analysis, ELISA cytokine assay, and
      quantitative real time-PCR were performed for VEGF, IL-6, VEGF receptors, and IL
      6 receptor gene expressions on HUVEC with wogonin treatment. Furthermore, in vivo
      chorioallantoic membrane (CAM) assay was applied to evaluate the percentage of
      new vessels formation. The results revealed that wogonin (10(-8)-10(-5) M)
      inhibited LPS-induced angiogenesis in a concentration-dependent manner. The mRNA
      and protein expressions of VEGF, VEGFR-2, IL-6, and sIL-6Ralpha were attenuated
      (P<0.05), but not VEGFR-1. In the LPS-induced CAM model, our data suggested that
      wogonin (10(-8)-10(-5) M) significantly decreased new vessel formation and
      vascular network (P<0.05). We conclude that wogonin suppresses both in vitro and
      in vivo LPS-induced angiogenesis, through VEGFR-2, but not VEGFR-1.

PMID- 16979124
TI  - Biological evaluation of sulfone derivatives as anti-inflammatory and tumor cells
      growth inhibitory agents.
AB  - A variety of sulfone derivatives including three dimethyl arylsulfonyl malonates
      (1-3), two bis-(arylethenesulfonyl)-vinyl benzenes (4 and 5) and a sulfone
      triazole (6) were evaluated for their anti-inflammatory as well as tumor cells
      growth inhibitory activities in vitro. The sulfone derivatives 1, 2, 3 and 6
      significantly and dose-dependently inhibited the production of inflammatory
      mediators such as nitric oxide (NO), and cytokines (tumor necrosis factor (TNF)
      alpha and interleukin (IL)-12), in lipopolysaccharide (LPS) and interferon (IFN)
      gamma activated murine peritoneal macrophages, without displaying cytotoxicity.
      The inhibitory mechanism is found through reducing iNOS protein expression. In
      addition, the derivatives 1-3 significantly arrest mitogen-stimulated spleen
      cells in G0/G1 stage, whereas compounds 4-6 blocked the same in the G2/M phase.
      Furthermore, the sulfone derivatives 3 and 6 showed dramatically reduction in the
      ratio of IFN-gamma to IL-4 production from mitogen-stimulated spleen cells. On
      the other hand, the novel compounds exhibited interesting cytotoxic activities
      against a panel of cell lines, particularly, 20 muM of compound 3 showed 50%
      cytotoxic effect on human hepatoma cell line, but has no effect on normal human
      peripheral blood mononuclear cells. In conclusion, compound 3 showed interesting
      anti-inflammatory and tumor cells growth inhibitory functions.

PMID- 16979125
TI  - 5-androstenediol stimulates multilineage hematopoiesis in rhesus monkeys with
      radiation-induced myelosuppression.
AB  - Total body ionizing irradiation (TBI) between 2-8 Gy causes the hematopoietic
      component of the acute radiation syndrome (ARS) in humans. Here we report on an
      exploratory study with 5-androstenediol (AED) in rhesus monkeys exposed to 4 Gy
      (60)Co gamma TBI. In this study, the effects of two formulations administered 3-4
      h after irradiation were evaluated. After radiation, severe neutropenia (<500
      neutrophils/microL), thrombocytopenia (<50,000 platelets/microL), and anemia
      (hemoglobin <8.0 g/dL) occurred in 6, 6, and 5 of the 6 control animals,
      respectively. In these 6 control animals, the median time to first day of each
      defined cytopenia was 8.5, 13, and 20 days and the median time to last occurrence
      was 22.5, 19.5 and 29.5 days, respectively. All treated groups had a decrease in
      the duration of severe neutropenia relative to vehicle control. All but one
      dosing regimen decreased the duration of thrombocytopenia and anemia. Five
      consecutive days of a 15 mg/kg intramuscular (IM) micro-particle preparation and
      a once weekly 15 mg/kg subcutaneous (SC) nanoparticle suspension generally
      provided the greatest radiation protection. AED, as a single agent, promotes
      multilineage hematopoietic recovery of the bone marrow. These data suggest that
      it may play an important therapeutic role in the management of acute radiation
      syndrome.

PMID- 16979126
TI  - Effect of horse gram lectin (Dolichos biflorus agglutinin) on degranulation of
      mast cells and basophils of atopic subjects: identification as an allergen.
AB  - Horse gram (Dolichos biflorus) is widely consumed in the tropical south Asian
      countries including rural areas of India. Since D. biflorus agglutinin (DBA) is
      an important dietary lectin in horse gram, we have studied its effect on the
      degranulation of mast cells and basophils of atopic subjects. Allergy to horse
      gram lectin has not been reported so far. Skin prick test (SPT) was performed
      with 100 microg/mL of DBA. DBA-specific IgE was detected by dot-blot, and ELISA.
      Histamine release (HR) assay was carried out using leukocytes from non-atopic and
      atopic subjects, and rat peritoneal exudate cells. Among the atopic group, 10 of
      48 subjects (21%) were found to be positive for DBA by SPT, and none were
      positive in the non-atopic group (n=20). Two subjects out of the ten who tested
      positive for DBA by SPT were found to be sensitized to DBA as revealed by the
      presence of specific IgE by ELISA and dot-blot. The HR was found to be 2- to 3
      fold higher in DBA-allergic subjects than in non-atopic and atopic subjects.
      Basophil HR by DBA was found to be similar in both non-atopic and atopic
      subjects. However, DBA induces activation of mast cells in vivo in a sub
      population (21%) of atopic subjects. Two subjects have been identified as having
      food allergy to horse gram based on the presence of DBA-specific IgE with a
      positive correlation to basophil HR. This is the first report of food allergy to
      horse gram, and DBA has been identified as an allergen.

PMID- 16979127
TI  - Inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression by
      flavonoids isolated from Tanacetum microphyllum.
AB  - Plant flavonoids show anti-inflammatory activity both in vitro and in vivo. Some
      flavonoids have been reported previously to inhibit nitric oxide (NO) and
      prostaglandin E2 (PGE2) production by suppressing inducible nitric oxide synthase
      (iNOS) and cyclooxygenase-2 (COX-2) expression. The present study focuses on the
      effect of various naturally occurring flavonoids (santin, ermanin, centaureidin
      and 5,3'-dihydroxy-4'-methoxy-7-methoxycarbonylflavonol) on modulation of
      lipopolysaccharide (LPS)-induced iNOS and COX-2 expression in RAW 264.7 cells.
      Western blotting showed that all flavonoids suppressed the induction of both iNOS
      and COX-2. Ermanin and 5,3'-dihydroxy-4'-methoxy-7-methoxycarbonylflavonol were
      the most potent inhibitors. This study suggests that inhibition of iNOS and COX-2
      expression by flavonoids may be one of the mechanisms responsible for their anti
      inflammatory effects, and that they may be potential agents for use in the
      treatment of inflammatory diseases.

PMID- 16979128
TI  - Immunological adjuvant activities of saponin extracts from the pods of Acacia
      concinna.
AB  - Pods of Acacia concinna (Leguminosae) contain several saponins. In this study,
      four saponin fractions which were acetone fraction (AAC), aqueous fraction (WAC),
      hydromethanolic fraction (HAC) and methanolic fraction (MAC) were generated and
      their haemolytic activities and surface activities were determined in comparison
      with quillaja saponin (QS). There were no significant differences between the
      haemolytic activities of MAC and QS. However, the surface tensions of MAC was
      significantly lower than QS (p < 0.001). Furthermore, the immunomodulatory effect
      and the adjuvant potential of MAC on the cellular and humoral immune response of
      BALB/c mice against ovalbumin were investigated. The splenocyte proliferations
      induced by MAC were significantly higher than QS at the concentrations of 200,
      400, 800 and 1000 microg/ml (p < 0.05). BALB/c mice were immunized subcutaneously
      either with OVA 20 microg alone or with OVA 20 microg combining with QS (10
      microg) or MAC (10 and 40 microg). Ten days after the second immunization,
      concanavalin A (Con A)-, pokeweed mitogen (PWM)-, and OVA-stimulated splenocyte
      proliferation and OVA-specific antibodies in serum were measured. The results
      suggested that MAC (40 microg) could activate T and B cells. In addition, OVA
      specific IgG, IgG1 IgG2a and IgG2b antibody levels in serum were significantly
      enhanced by MAC (40 microg) as compared with OVA control group (p < 0.001). This
      finding suggested that MAC might be effect on Th1 and Th2 helper T cells. In
      conclusion, the results indicated that MAC at a dose of 40 microg could be used
      as vaccine adjuvant to increase immune responses.

PMID- 16979129
TI  - Involvement of cyclooxygenase-2 in allergic nasal inflammation in rats.
AB  - This study was undertaken to investigate the involvement of cyclooxygenase-2 (COX
      2) in allergic nasal inflammation in actively sensitized rats. An allergic
      rhinitis model was developed by the repeated topical application of antigen into
      the nasal cavities in the sensitized rats. The severity of allergic rhinitis was
      studied by measuring the nasal behavior, as well as electroencephalogram (EEG)
      activity by antigen challenge. The electrodes were implanted chronically into the
      bilateral olfactory bulb of the rats and the EEG was measured monopolarly with an
      electroencephalograph (EEG, Nohon Kohden, Japan). The intranasal application of
      antigen caused the increase of nasal allergic signs as well as an EEG spike in a
      dose-dependent fashion, and at a dose of 50 microg/site, it showed a significant
      effect. The responses induced by the antigen were evaluated with certain drugs,
      etodolac (a selective COX-2 inhibitor), indomethacin (a non-selective COX
      inhibitor), ramatroban (a thromboxane A2 receptor antagonist) and zafirlukast (a
      cys-leukotriene receptor antagonist). Etodolac showed the inhibition of nasal
      behavior and EEG spike in a dose-related fashion, and at doses of 3 and 10 mg/kg,
      it showed a significant effect. Moreover, ramatroban also caused the dose-related
      inhibition of nasal behavior and EEG spike induced by antigen. On the other hand,
      both indomethacin and zafirlukast had no effects on the responses induced by
      antigen, even at a higher dose. Therefore, it can be concluded that
      cyclooxygenase-2 actively participates in the allergic nasal inflammation in
      actively sensitized rats.

PMID- 16979130
TI  - Botulinum toxin as a novel addition to anti-arthritis armamentarium: an
      experimental study in rabbits.
AB  - OBJECTIVE: This study aims to investigate the effects of intra-articular
      botulinum toxin. METHODS: Osteoarthritis was induced in both knees of 20 rabbits
      by transecting the anterior cruciate ligament under intramuscular anesthesia with
      ketamine and xylazine. Botulinum toxin, at a dose of 2.5 microg/ml (0.6 ml) and
      physiologic saline solution (0.6 ml) were injected into the right and left knees,
      respectively, three times with a 1week interval between each injection. The
      rabbits were sacrificed in the 12th week via high dose anesthesia to remove the
      distal femora for histological evaluation using the Mankin scale and Safranin O.
      RESULTS: The mean cartilage areas calculated in toxin- and saline-injected knees
      differed significantly (1.097 mm(2) and 0.477 mm(2), respectively; P<0.05). The
      overall mean Mankin score was significantly lower in toxin-injected knees (3.57
      versus11.14; P<0.05). Although there were no significant differences between the
      two groups with respect to cellular abnormality, matrix staining, and tidemark
      continuity (P>0.05), the mean scores for the structure of the cartilage were
      significantly different (0.86 versus 4.43; P<0.05). The integrity of the tidemark
      was preserved in all the toxin-administered knees, though a notable disruption
      was observed in four control knees. CONCLUSIONS: Our results suggest that
      botulinum toxin delays the development of osteoarthritis at early stages through
      exerting a chondroprotective effect.

PMID- 16979131
TI  - Cytotoxicity and antigenicity of antimicrobial synthesized peptides derived from
      the beetle Allomyrina dichotoma defensin in mice.
AB  - Synthetic peptides, peptides A (Arg-Leu-Tyr-Leu-Arg-Ile-Gly-Arg-Arg-NH(2)) and B
      (Arg-Leu-Arg-Leu-Arg-Ile-Gly-Arg-Arg-NH(2)), derived from the beetle Allomyrina
      dichotoma defensin, have antimicrobial activities. Immunotoxicological effect of
      these peptides was evaluated by cytotoxicity of mouse peritoneal macrophages. In
      addition, antigenicity of these peptides was studied by evaluating antibody
      responses in mice immunized with these peptides. The toxicity of peptide A toward
      mouse peritoneal cells was less than that of polymyxin B, when morphologically
      evaluated in a cytotoxicity test. Almost all of mice injected intraperitoneally
      (i.p.) with either peptide A or B at 50-150 mg/kg survived, whereas all mice
      injected i.p. with polymyxin B at the doses of more than 25 mg/kg died within 24
      h. Interestingly, almost all of mice injected intravenously with these peptides
      at the doses of 10 and 25 mg/kg also survived. Furthermore, mice immunized with
      these peptides conjugated with keyhole limpet hemocyanin (KLH) showed little or
      negligible anti-peptide A or B antibody production, although anti-KLH antibody
      was significantly produced. The results indicated that peptides A and B were less
      cytotoxic than polymyxin B and also had poor antigenicity to produce specific
      antibody in mice.

PMID- 16979132
TI  - The effect of age, gender and driver status on pedestrians' intentions to cross
      the road in risky situations.
AB  - The theory of planned behaviour (TPB) has been used successfully in the past to
      account for pedestrians' intentions to cross the road in risky situations.
      However, accident statistics show age and gender differences in the likelihood of
      adult pedestrian accidents. This study extends earlier work by examining the
      relative importance of the model components as predictors of intention to cross
      for four different adult age groups, men, women, drivers and nondrivers. The
      groups did not differ in the extent to which they differentiated between two
      situations of varying perceived risk. The model fit was good, but accounted for
      less of the variance in intention for the youngest group (17-24) than for other
      age groups. Differences between the age groups in intention to cross seemed to be
      due to differences in perceived value of crossing rather than differences in
      perceived risk. Women were less likely to intend to cross than men and perceived
      more risk, and there were important age, gender and driver status differences in
      the importance of the TPB variables as predictors of intention. A key implication
      of these findings is that road safety interventions need to be designed
      differently for different groups.

PMID- 16979133
TI  - Sensitivity analysis and error structure of progress curves.
AB  - Both the sensitivity of the monitored signal in progress curves to variations in
      enzyme concentration and the standard deviation of this signal were analyzed as a
      function of the proportion of transformed substrate. Three enzymes catalyzing
      essentially irreversible reactions were used as model systems: HIV-1 protease,
      glutathione reductase, and glutathione transferase. For all enzymes analyzed, the
      sensitivity was maximal when 60-80% of the substrate had been transformed. The
      standard deviation of reaction progress curve data replicates was also maximal at
      these substrate conversion levels, a result that was attributed to the influence
      of the sensitivity to random dispersion of the enzyme concentration. On this
      basis, we developed a model for the standard deviation of reaction progress
      curves that gave a good description of the experimental data and efficiently
      reduced the heteroscedasticity of residuals in a weighted fit of progress curves.
      This standard deviation model can be used for obtaining more efficient parameter
      estimates, to simulate noise in Monte Carlo procedures, and to delineate
      detection limits of enzyme inhibition. The transient increases in the sensitivity
      and in the standard deviation in progress curves are proposed to be features
      common to most enzymatic assays.

PMID- 16979134
TI  - Construction of a deletion strain and expression vector for the Escherichia coli
      NADH:ubiquinone oxidoreductase (Complex I).
AB  - Complex I of Escherichia coli is encoded by 13 consecutive genes, called the nuo
      operon. A chromosomal deletion of all nuo genes has been achieved by homologous
      recombination. A vector that encodes all of the nuo genes has been constructed,
      and it expresses a functional enzyme.

PMID- 16979135
TI  - HSP90beta is involved in signaling prolactin-induced apoptosis in newt testis.
AB  - We have shown in vivo and in vitro that prolactin induces apoptosis in the 7th
      generation of spermatogonia during newt spermatogenesis, but the underlying
      molecular mechanism remained unknown. To determine the role of heat shock protein
      (HSP) 90beta, a molecular chaperone for client proteins in signal transduction
      and transcriptional regulation, in prolactin-induced apoptosis, we cloned
      HSP90beta cDNA from newt testis. HSP90beta was detected highly at spermatogonial
      stage and in both the membrane and cytosol fractions only in germ cell-enriched
      fraction, while prolactin receptor was expressed in the membrane fraction of only
      germ cells. Co-immunoprecipitation demonstrated that HSP90beta associated
      constitutively with prolactin receptor on the plasma membrane of germ cells,
      suggesting that prolactin receptor is also one of the client proteins for
      HSP90beta. Inhibition of HSP90beta function by geldanamycin was shown to promote
      spermatogonial apoptosis. Taken together, these results suggest that HSP90beta is
      involved in signaling prolactin-induced apoptosis through the receptor.

PMID- 16979136
TI  - Ubiquitin ligase gp78 increases solubility and facilitates degradation of the Z
      variant of alpha-1-antitrypsin.
AB  - Deficiency of circulating alpha-1-antitrypsin (AAT) is the most widely recognized
      abnormality of a proteinase inhibitor that causes lung disease. AAT-deficiency is
      caused by mutations of the AAT gene that lead to AAT protein retention in the
      endoplasmic reticulum (ER). Moreover, the mutant AAT accumulated in the ER
      predisposes the homozygote to severe liver injuries, such as neonatal hepatitis,
      juvenile cirrhosis, and hepatocellular carcinoma. Despite the fact that mutant
      AAT protein is subject to ER-associated degradation (ERAD), yeast genetic studies
      have determined that the ubiquitination machinery, Hrd1/Der3p-cue1p-Ubc7/6p,
      which plays a prominent role in ERAD, is not involved in degradation of mutant
      AAT. Here we report that gp78, a ubiquitin ligase (E3) pairing with mammalian
      Ubc7 for ERAD, ubiquitinates and facilitates degradation of ATZ, the classic
      deficiency variant of AAT having a Z mutation (Glu 342 Lys). Unexpectedly, gp78
      over-expression also significantly increases ATZ solubility. p97/VCP, an AAA
      ATPase essential for retrotranslocation of misfolded proteins from the ER during
      ERAD, is involved in gp78-mediated degradation of ATZ. Surprisingly, unlike other
      ERAD substrates that cause ER stress leading to apoptosis when accumulated in the
      ER, ATZ, in fact, increases cell proliferation when over-expressed in cells. This
      effect can be partially inhibited by gp78 over-expression. These data indicate
      that gp78 assumes multiple unique quality control roles over ATZ, including the
      facilitation of degradation and inhibition of aggregation of ATZ.

PMID- 16979137
TI  - Immunoglobulin E-independent activation of mast cell is mediated by Mrg
      receptors.
AB  - Mast cells play a central role in inflammatory and allergic reactions by
      releasing inflammatory mediators through two main pathways, immunoglobulin E
      dependent and -independent activation. In the latter, mast cells are activated by
      a diverse range of basic molecules, including peptides and amines such as
      substance P, neuropeptide Y, and compound 48/80. These secretagogues are thought
      to activate the G proteins in mast cells through a receptor-independent
      mechanism. Here, we report that the basic molecules activate G proteins through
      the Mas-related gene (Mrg) receptors on mast cells, leading to mast cell
      degranulation. We suggest that one of the Mrg receptors, MrgX2, has an important
      role in regulating inflammatory responses to non-immunological activation of
      human mast cells.

PMID- 16979138
TI  - Inhibition of tumor cell-induced platelet aggregation using a novel anti
      podoplanin antibody reacting with its platelet-aggregation-stimulating domain.
AB  - The mucin-type sialoglycoprotein, podoplanin (aggrus), is a platelet-aggregating
      factor on cancer cells. We previously described up-regulated expression of
      podoplanin in malignant astrocytic tumors including glioblastoma. Its expression
      was associated with tumor malignancy. In the present study, we investigated
      podoplanin expression and platelet-aggregating activities of glioblastoma cell
      lines. First, we established a highly reactive anti-podoplanin antibody, NZ-1,
      which inhibits podoplanin-induced platelet aggregation completely. Of 15
      glioblastoma cell lines, LN319 highly expressed podoplanin and induced platelet
      aggregation. Glycan profiling using a lectin microarray showed that podoplanin on
      LN319 possesses sialic acid, which is important in podoplanin-induced platelet
      aggregation. Interestingly, NZ-1 neutralized platelet aggregation by LN319. These
      results suggest that podoplanin is a main reason for platelet aggregation induced
      by LN319. We infer that NZ-1 is useful to determine whether platelet aggregation
      is podoplanin-specific or not. Furthermore, podoplanin might become a therapeutic
      target of glioblastoma for antibody-based therapy.

PMID- 16979139
TI  - Partial agonists as therapeutic agents at neuronal nicotinic acetylcholine
      receptors.
AB  - Improved understanding of how brain function is altered in neurodegenerative
      disease states, pain and conditions, such as schizophrenia and attention deficit
      disorder, has highlighted the role of nicotinic acetylcholine receptors (nAChRs)
      in these conditions and identified them as promising therapeutic targets. nAChRs
      are widely expressed throughout the peripheral and central nervous system, and
      this widespread nature underlines the need for new ligands with different
      selectivities and pharmacological profiles if we are to avoid the adverse side
      effects associated with many of the nAChR modulators currently identified.
      Partial agonists have the unique property of being able to act both as agonists
      or antagonists depending on the concentration of endogenous neurotransmitter.
      Moreover, the agonist action of partial agonists has a 'ceiling' effect, giving
      them a large safety margin and making them an attractive proposition for
      therapeutic molecules. Partial agonists of nAChRs are currently being developed
      as a nicotine replacement therapy for smoking cessation and for the treatment of
      a number of neurological diseases associated with a loss of cholinergic function.
      This commentary will discuss the pharmacological properties of partial agonists
      and review recent research developments in the field of partial agonists acting
      at nicotinic receptors.

PMID- 16979140
TI  - Inhibition of phosphatidylinositol 3-kinase-mediated glucose metabolism coincides
      with resveratrol-induced cell cycle arrest in human diffuse large B-cell
      lymphomas.
AB  - An abnormally high rate of aerobic glycolysis is characteristic of many
      transformed cells. Here we report the polyphenolic compound, resveratrol,
      inhibited phosphatidylinositol 3-kinase (PI-3K) signaling and glucose metabolism,
      coinciding with cell-cycle arrest, in germinal center (GC)-like LY1 and LY18
      human diffuse large B-cell lymphomas (DLBCLs). Specifically, resveratrol
      inhibited the phosphorylation of Akt, p70 S6K, and S6 ribosomal protein on
      activation residues. Biochemical analyses and nuclear magnetic resonance
      spectroscopy identified glycolysis as the primary glucose catabolic pathway in
      LY18 cells. Treatment with the glycolytic inhibitor 2-deoxy-D-glucose, resulted
      in accumulation of LY18 cells in G0/G1 -phase, underscoring the biological
      significance of glycolysis in growth. Glycolytic flux was inhibited by the PI-3K
      inhibitor LY294002, suggesting a requirement for PI-3K activity in glucose
      catabolism. Importantly, resveratrol treatment resulted in inhibition of
      glycolysis. Decreased glycolytic flux corresponded to a parallel reduction in the
      expression of several mRNAs encoding rate-limiting glycolytic enzymes. These
      results are the first to identify as a mechanism underlying resveratrol-induced
      growth arrest, the inhibition of glucose catabolism by the glycolytic pathway.
      Taken together, these results raise the possibility that inhibition of signaling
      and metabolic pathways that control glycolysis might be effective in therapy of
      DLBCLs.

PMID- 16979141
TI  - Reduced serotonin-1A receptor binding in social anxiety disorder.
AB  - BACKGROUND: Results from studies in serotonin-1A (5-HT1A) knockout mice and
      previous positron emission tomography (PET) studies in humans imply a role for 5
      HT1A receptors in normal state anxiety as well as in certain anxiety disorders.
      The objective of this study was to investigate 5-HT1A receptor binding potential
      (BP) in social anxiety disorder (SAD). METHODS: Using PET and [carbonyl-11C]WAY
      100635, we compared a homogeneous group of 12 unmedicated, male SAD patients with
      18 healthy control subjects (HC). A multivariate ANOVA with all regional BP
      values as dependent variables, age and four radiochemical variables as covariates
      was performed. RESULTS: We found a significantly lower 5-HT1A BP in several
      limbic and paralimbic areas but not in the hippocampus (p = .234) of SAD
      patients. The difference in 5-HT1A binding was most significant in the amygdala (
      21.4%; p = .003). There was also a more than 20% lower 5-HT(1A) BP of SAD
      patients in the anterior cingulate cortex (p = .004), insula (p = .003), and
      dorsal raphe nuclei (p = .030). CONCLUSIONS: The lower 5-HT1A binding in the
      amygdala and mesiofrontal areas of SAD patients is consistent with 1) preclinical
      findings of elevated anxiety in 5-HT1A knockout mice, 2) a previous PET study in
      healthy volunteers showing an inverse correlation between 5-HT1A BP and state
      anxiety, and 3) another human PET study in patients with panic disorder showing
      reduced 5-HT1A binding, thus corroborating the potential validity of 5-HT1A
      receptors as targets in the treatment of human anxiety disorders.

PMID- 16979143
TI  - Characterizing exploration behavior in spatial neglect: omissions and repetitive
      search.
AB  - In search tasks, patients with spatial neglect typically fail to respond to
      stimuli on the contralesional side. Such behavior has been associated with
      hyperattention to the ipsilesional side and a deficit in disengaging from
      attended stimuli. The present study investigated whether such explanations can
      also account for a further kind of behavior frequently shown by neglect patients:
      repetitive returns to previously indicated stimuli, particularly on the
      ipsilesional side. A group of neglect patients was tested along with a group of
      healthy participants and a patient control group without neglect. Participants
      performed an exploration task in which they searched for targets defined by their
      shape or for all stimuli either with the aid of vision or blindfolded. The
      results showed differential effects of reducing the salience of visual stimuli by
      blindfolding. For a subgroup of patients, detection rate improved, while for
      others the percentage of omissions increased. However, contrary to the control
      groups, blindfolding had no effect on repetitive search in the neglect group,
      inconsistent with hyperattention, a disengage or impaired working memory
      deficits. The rate of repetitive returns to previously indicated locations did
      not seem to be associated with the percentage of omitted stimuli, suggesting that
      repetitive returns may be best explained by a disruption of systematic search and
      lack of volitional control in spatial neglect. The results further underline the
      importance of considering repetitive search behavior in addition to omissions in
      standard neglect assessments.

PMID- 16979142
TI  - The effects of apomorphine and D-amphetamine on striatal c-Fos expression in
      Sprague-Dawley and Long Evans rats and their F1 progeny.
AB  - We previously reported that Sprague-Dawley (SD) rats are significantly more
      sensitive than Long Evans (LE) rats to disruption of prepulse inhibition (PPI) of
      the startle reflex by the dopamine agonists, apomorphine (APO) and D-amphetamine
      (AMPH). This susceptibility is inherited through F1 (SD x LE) and N2 backcross
      (F1 x SD) generations via an orderly pattern (SD>N2>F1>LE). Here we examined
      systemic APO (0.5 mg/kg) and AMPH (4.5 mg/kg) modulation of neural activity in
      four regions of the striatum suspected to be involved in the dopaminergic
      regulation of PPI - dorsolateral (dlCPu) and medial (mCPu) caudate/putamen and
      core (NACc) and medial shell (NACms) regions of nucleus accumbens - under
      conditions that mimicked those used to assess PPI. Immunohistochemical
      quantification of c-Fos protein expression was used as the surrogate measure of
      neural activity in SD and LE rats and their F1 crosses. Vehicle-treatment showed
      significant regional differences in Fos expression, particularly between the
      dlCPu and the other three areas, but no strain-related differences were observed.
      Three of four brain areas examined (dlCPu, mCPu and NACc) exhibited drug-induced
      changes in Fos expression--APO decreased and AMPH increased Fos expression in
      each region. The aggregate effect across these three regions revealed Fos
      expression to be significantly greater in LE compared to SD rats for both drugs,
      with F1 rats intermediate. This pattern of inheritance (LE>F1>SD) reveals an
      inverse relationship between striatal Fos expression and PPI sensitivity for
      these drugs; and a positive relationship with reported heritable differences in
      D2-linked G-protein binding in the CPu and NACc, and with locomotor
      activation/suppression by AMPH and APO.

PMID- 16979145
TI  - Enhancement of hippocampal long-term potentiation induced by cocaine self
      administration is maintained during the extinction of this behavior.
AB  - Drug addiction may involve learning and memory processes requiring the
      participation of hippocampal formation. One of the best studied examples of
      hippocampal synaptic plasticity is the long-term potentiation (LTP) which usually
      occurs when hippocampal synapses are stimulated with high-frequency stimulation.
      The aim of this work has been to study the effect of extinction of cocaine self
      administration behavior on synaptic plasticity in rat hippocampal slices. LTP was
      induced using a tetanization paradigm consisting of a single train of high
      frequency (100 Hz) stimulation for one second. This tetanization protocol evoked
      a greater and more perdurable LTP in slices obtained after 10 days of extinction
      of cocaine self-administration (1 mg/kg/injection) than that elicited in slices
      from saline self-administering (0.9% NaCl) animals. In addition, this LTP
      facilitation in animals which have followed the cocaine self-administration
      extinction protocol was very similar to that obtained in slices from cocaine self
      administering animals. These results suggest that chronic cocaine self
      administration induces enduring neuroadaptive changes in hippocampal synaptic
      plasticity which last even after the extinction of this behavior and that they
      may be involved in cocaine dependence.

PMID- 16979144
TI  - Hearing suppression induced by electrical stimulation of human auditory cortex.
AB  - In the course of performing electrical stimulation functional mapping (ESFM) in
      neurosurgery patients, we identified three subjects who experienced hearing
      suppression during stimulation of sites within the superior temporal gyrus (STG).
      One of these patients had long standing tinnitus that affected both ears. In all
      subjects, auditory event related potentials (ERPs) were recorded from chronically
      implanted intracranial electrodes and the results were used to localize auditory
      cortical fields within the STG. Hearing suppression sites were identified within
      anterior lateral Heschl's gyrus (HG) and posterior lateral STG, in what may be
      auditory belt and parabelt fields. Cortical stimulation suppressed hearing in
      both ears, which persisted beyond the period of electrical stimulation. Subjects
      experienced other stimulation-evoked perceptions at some of these same sites,
      including symptoms of vestibular activation and alteration of audio-visual speech
      processing. In contrast, stimulation of presumed core auditory cortex within
      posterior medial HG evoked sound perceptions, or in one case an increase in
      tinnitus intensity, that affected the contralateral ear and did not persist
      beyond the period of stimulation. The current results confirm a rarely reported
      experimental observation, and correlate the cortical sites associated with
      hearing suppression with physiologically identified auditory cortical fields.

PMID- 16979146
TI  - Brain-derived neurotrophic factor gene polymorphism (Val66Met) and citalopram
      response in major depressive disorder.
AB  - The brain-derived neurotrophic factor (BDNF) gene is a candidate gene for
      influencing the clinical response to treatment with antidepressants. The purpose
      of this study was to determine the relationship between the Val66Met polymorphism
      in the BNDF gene and the response to citalopram in a Korean population with major
      depressive disorder (MDD). Citalopram was administered for 8 weeks to the 83
      patients who completed this study. We found that the genotype, allele, and allele
      carrier distributions for the Val66Met polymorphism differed significantly
      between responders (Rp) and nonresponders (Non-Rp). The frequency of M-allele
      carriers (VM+MM) was higher in Rp than in Non-Rp (chi(2)=8.926, p=0.003,
      OR=4.375, 95%CI=1.609-11.892), as was the M-allele frequency (chi(2)=6.879,
      p=0.009, OR=2.500, 95%CI=1.249-5.005). There were also significant differences in
      the core (p=0.012) and activity (p=0.008) scores. Patients carrying the M-allele
      had a lower score. Also, patients carrying the M-allele tended to have lower
      psychic anxiety (p=0.072). The percentage change in the total HAM-D score was
      higher for M-allele carriers (VM+MM allele) than for noncarriers (p=0.034) after
      8 weeks of medication. We found that the genotype, allele, and allele-carrier
      distributions did not differ significantly between MDD patients and normal
      controls. These results suggest that the Val66Met polymorphism of BDNF is
      associated with citalopram efficacy, with M-allele carriers responding better to
      citalopram treatment. Moreover, the Val66Met polymorphism was correlated with
      improvements in core, activity, and psychic anxiety symptoms.

PMID- 16979147
TI  - Glucose metabolites in the striatum of freely behaving rats following infusion of
      elevated potassium.
AB  - The outcome of patients with traumatic brain injury (TBI) can be predicted by the
      extracellular potassium concentration and the change in energy homeostasis. In
      this study, the authors investigated the effects of high potassium concentrations
      on extracellular levels of glucose, pyruvate and lactate in the rat striatum.
      Applying artificial cerebrospinal fluid (ACSF) enriched with 120 mM potassium by
      reverse microdialysis leads to an increase in lactate and reduction in glucose
      and pyruvate. Consequently, the lactate to pyruvate ratio was also increased.
      These data are discussed in the context of recent studies on lactate/pyruvate
      conversion and the potential mechanisms whereby high potassium could affect this
      equilibrium. We conclude that ischemic-like events are unlikely to explain these
      K(+)-induced changes.

PMID- 16979148
TI  - Gap junction heterogeneity in reentrant ventricular tachycardia.

PMID- 16979149
TI  - Anti-cyclic citrullinated peptide (CCP) antibodies in patients with long-standing
      rheumatoid arthritis and their relationship with extra-articular manifestations.
AB  - OBJECTIVES: To evaluate frequency of anti-cyclic citrullinated peptide antibodies
      (anti-CCP) in long-standing rheumatoid arthritis (LsRA) patients and their
      relationship with extra-articular manifestations of rheumatoid arthritis (RA), in
      addition to comparing frequency of anti-CCP antibodies in early RA (ERA) and LsRA
      group. DESIGN AND METHODS: One hundred and fifteen consecutive RA patients were
      included in the study as having LsRA because their disease duration was longer
      than 3 years. Thirty-nine consecutive patients with RA were included in the study
      as having ERA (<3 years). Also, 64 individuals were included in the study as
      healthy controls to verify the specificity and sensitivity of anti-CCP
      antibodies. Anti-CCP antibody and rheumatoid factor (RF) were evaluated with
      enzyme-linked immunosorbent assay kits and standard nephelometry methods,
      respectively. Extra-articular manifestations were diagnosed by relevant criteria.
      RESULTS: The total number of patients with extra-articular manifestations was
      found to be 45 (39%). No significant difference was found between LsRA group and
      ERA group in terms of extra-articular manifestations. There were no differences
      between both groups regarding the number of patients with positive anti-CCP
      antibodies and the levels of anti-CCP antibodies. In LsRA group, there was a
      positive correlation between erosion and disease duration (r=0.24, p<0.01),
      between erosion and RF (r=0.29, p<0.002), and between erosion and anti-CCP
      antibody (r=0.21, p<0.02). Positive correlations between RF and anti-CCP antibody
      (r=0.32, p<0.0001), as well as between subcutaneous nodule and lung involvement
      (r=0.24, p<0.008), were found in the LsRA group. However, no positive correlation
      could be found between anti-CCP antibody positivity and extra-articular organ
      involvement, either cumulatively or separately. CONCLUSIONS: Although anti-CCP
      antibodies are associated with the severity of the disease and erosion, they do
      not seem to have much linkage with extra-articular manifestations of RA.

PMID- 16979150
TI  - Ghrelin and glucoregulatory hormone responses to a single circuit resistance
      exercise in male college students.
AB  - INTRODUCTION: It has been suggested that ghrelin may play a role in growth
      hormone (GH) secretion to exercise. OBJECTIVE: The present study was designed to
      examine the effects of a single bout of circuit resistance exercise on plasma
      glucose, ghrelin, GH, and c-peptide, and cortisol. DESIGN AND METHODS: Fourteen
      volunteer male physical education students completed a single bout circuit
      resistance training (10 exercises, three circuits, and at 60% of 1-RM). Blood
      samples were collected before, immediately after the exercise, and 24-h following
      the exercise protocol. RESULTS: GH, glucose, and c-peptide showed a significant
      increase immediately after exercise and returned to pre exercise values over
      time. Plasma ghrelin showed a significant decrease immediately after the exercise
      and increased significantly 24-h following the exercise. CONCLUSION: In
      conclusion, a decrease in plasma ghrelin following a single bout of circuit
      resistance exercise indicates that an increase in GH is not related to plasma
      ghrelin levels. An acute exercise-induced hyperphagia during the long-recovery
      was considered.

PMID- 16979151
TI  - Intermediary metabolism in sea urchin: the first inferences from the genome
      sequence.
AB  - The genome sequence of the purple sea urchin Strongylocentrotus purpuratus
      recently became available. We report the results of functional annotation and
      initial analysis of more than 2300 proteins predicted to be involved in
      metabolite transport and enzymatic conversion in sea urchin. The comparison of
      various reconstructed biosynthetic and catabolic pathways in sea urchin to those
      known in other genomes suggests the overall similarity of the sea urchin
      metabolism to that of the vertebrates, with relatively small but non-trivial
      differences from both vertebrates and protostomes. There are several examples of
      two parallel, non-orthologous solutions for the same molecular function in sea
      urchin, in contrast with the other completely sequenced metazoans that tend to
      contain just one version of the same function. There are also genes that appear
      to be close phylogenetic neighbors of plant or bacterial homologs, as opposed to
      homologs in other Metazoa. The evolutionary and functional significance of these
      variations is discussed.

PMID- 16979152
TI  - Maternal deployment of the embryonic SKN-1-->MED-1,2 cell specification pathway
      in C. elegans.
AB  - We have previously shown that the MED-1,2 divergent GATA factors act apparently
      zygotically to specify the fates of the MS (mesoderm) and E (endoderm) sister
      cells, born at the 7-cell stage of C. elegans embryogenesis. In the E cell, MED
      1,2 activate transcription of the endoderm-promoting end-1 and end-3 genes. We
      demonstrate by in situ hybridization that med transcripts accumulate both in the
      EMS cell and in the maternal germline in a SKN-1-dependent manner. Removal of
      zygotic med function alone results in a weakly impenetrant loss of endoderm.
      However, med-1,2(-) embryos made by mothers in which germline med transcripts
      have been abrogated by transgene cosuppression fail to make endoderm 50% of the
      time, similar to the phenotype seen by RNAi. We also find that reduction of Med
      or End activity results in aberrant numbers of intestinal cells in embryos that
      make endoderm. We further show that regulation of the paralogous end-1 and end-3
      genes consists of both shared and distinct inputs, and that END-3 activates end-1
      expression. Our data thus reveal three new properties of C. elegans endoderm
      specification: both maternal and zygotic activities of the med genes act to
      specify endoderm, defects in endoderm specification also result in defects in gut
      cell number, and activation of the paralogous end-1 and end-3 genes differs
      qualitatively in the relative contributions of their upstream regulators.

PMID- 16979153
TI  - Retinoic acid signalling is required for specification of pronephric cell fate.
AB  - The mechanisms by which a subset of mesodermal cells are committed to a
      nephrogenic fate are largely unknown. In this study, we have investigated the
      role of retinoic acid (RA) signalling in this process using Xenopus laevis as a
      model system and Raldh2 knockout mice. Pronephros formation in Xenopus embryo is
      severely impaired when RA signalling is inhibited either through expression of a
      dominant-negative RA receptor, or by expressing the RA-catabolizing enzyme XCyp26
      or through treatment with chemical inhibitors. Conversely, ectopic RA signalling
      expands the size of the pronephros. Using a transplantation assay that inhibits
      RA signalling specifically in pronephric precursors, we demonstrate that this
      signalling is required within this cell population. Timed antagonist treatments
      show that RA signalling is required during gastrulation for expression of Xlim-1
      and XPax-8 in pronephric precursors. Moreover, experiments conducted with a
      protein synthesis inhibitor indicate that RA may directly regulate Xlim-1. Raldh2
      knockout mouse embryos fail to initiate the expression of early kidney-specific
      genes, suggesting that implication of RA signalling in the early steps of kidney
      formation is evolutionary conserved in vertebrates.

PMID- 16979154
TI  - To the editor.

PMID- 16979155
TI  - Altered hippocampal gene expression 2 days after general anesthesia in rats.
AB  - We profiled changes in gene expression in the hippocampus 2 days after a 4 h
      general anesthetic with isoflurane and nitrous oxide. Eighteen month old Fisher
      344 rats were anesthetized for 4 h with 1.2% isoflurane and 70% nitrous oxide
      (N=9) whereas control rats breathed 30% oxygen for 4 h (N=9). Rats were
      sacrificed 48 h later and RNA extracted from the hippocampus for gene expression
      profiling. Three gene arrays were used per group, with samples prepared by
      pooling RNA from three rats. Differentially expressed genes were analyzed based
      on a weighted error statistical model. Microarray results for 6 differentially
      expressed genes were verified with reverse transcriptase polymerase chain
      reaction. Compared to unanesthetized controls, 297 genes were differentially
      expressed 2 days following anesthesia (P<0.05). Of these, 113 are named genes;
      64% were up-regulated and 36% were down-regulated. The majority of differentially
      expressed genes are implicated in cell stress and replication, signal
      transduction, transcription, protein biosynthesis, cell structure, and
      metabolism. The correlation between fold changes on array and reverse
      transcriptase polymerase chain reaction was good (R2=0.85) for the 6 genes
      examined with both methods. These results demonstrate that in rats general
      anesthesia is associated with persistent changes in hippocampal gene expression,
      suggesting that recovery of the brain from anesthesia is considerably slower than
      generally recognized.

PMID- 16979156
TI  - Selection of new chemical entities with decreased potential for adverse drug
      reactions.
AB  - Adverse drug reactions, such as hepatotoxicity, blood dyscrasias and
      hypersensitivity are a major obstacle for the use and the development of new
      medicines. Many forms of organ-directed toxicity can arise from the bioactivation
      of drugs to so-called chemically reactive metabolites, which can modify tissue
      macromolecules. It is well established that the toxicities of model hepatotoxins,
      such as acetaminophen, furosemide, bromobenzene and methapyrilene can be
      correlated with the generation of chemically reactive metabolites, which can be
      detected by measurement of the irreversible binding of radiolabelled material to
      hepatic protein and/or the detection of stable phase II metabolites such as
      glutathione conjugates. The basic chemistry of the reaction of such metabolites
      with model nucleophiles is relatively well understood. A major challenge is to
      define how certain reactive intermediates may chemically modify critical proteins
      and how modification of specific amino acids may alter protein function which in
      turn may affect cell signalling, regulation, defence, function and viability.
      This in turn will determine whether or not bioactivation will result in a
      particular form of drug-induced injury. It is now clear that even relatively
      simple reactive intermediates can react in a discriminative manner with
      particular cellular proteins and even with specific amino acids within those
      proteins. Therefore both non-covalent, as well as covalent bonds will be
      important determinants of the target protein for a particular reactive
      metabolite. Mammalian cells have evolved numerous defence systems against
      reactive intermediates. Sensitive redox proteins such as Nrf-2 recognize
      oxidative stress and electrophilic agents. This is achieved by chemical
      modification of cysteine groups within keap-1, which normally forms an inactive
      heterodimer with Nrf-2. Modification of keap-1 releases Nrf-2 that translocates
      to the nucleus and effects gene transcription of a number of genes involved in
      the detoxication of chemically reactive metabolites. Diminution of protein
      function can occur by either covalent modification of nucleophilic amino acids
      (e.g. cysteine, lysine, histidine etc.) or oxidation of thiols, which can be
      reversible or irreversible. In the case of acetaminophen, more than 30 target
      proteins have been identified and for several of them, corresponding alterations
      in protein function have been defined in the context of tissue necrosis.
      Alternatively, protein modification may induce signalling systems which initiate
      cell death, an immune response or to an altered tissue genotype.

PMID- 16979157
TI  - Aldose reductase inhibitor zopolrestat restores allergic hyporesponsiveness in
      alloxan-diabetic rats.
AB  - This study was undertaken to investigate the role of the aldose reductase in the
      refractoriness of diabetic rats to allergic inflammation. Wistar rats were
      actively sensitized with a mixture of Al(OH)3 plus ovalbumin and intrapleurally
      challenged with ovalbumin, 14 days later. Diabetes was induced by intravenous
      injection of alloxan into fasted rats, 7 days before sensitization, and the
      aldose reductase inhibitor zopolrestat was administered after 3 days of diabetes
      induction, once a day during 18 consecutive days. The treatment with zopolrestat
      restored antigen-induced protein extravazation and mast cell degranulation in the
      pleural cavity of diabetic sensitized rats. Zopolrestat also significantly
      reversed the suppression in the increase of total and specific levels of serum
      immunoglobulin E (IgE) noted in sensitized animals under conditions of diabetes.
      In addition, we noted that the drop in the pleural mast cell numbers as well as
      the increase in serum corticosterone levels in diabetic rats were inhibited by
      the drug. Our findings show that zopolrestat restored the hyporesponsiveness of
      diabetic rats to antigen provocation, in parallel with impairment of alloxan
      induced mast cell depletion and hypercorticolism, indicating that polyol pathway
      activity seems to play an important role in these phenomena.

PMID- 16979158
TI  - Effects of G-CSF on cardiac remodeling and arterial hyperplasia in rats.
AB  - Although granulocyte colony-stimulating factor (G-CSF) has been shown to prevent
      cardiac remodeling after acute myocardial infarction, the mechanism and safety of
      G-CSF treatment acute myocardial infarction remain controversial. The purpose of
      the present study was to investigate in a rat model the mechanisms underlying the
      beneficial effect of G-CSF in acute myocardial infarction and to determine
      whether G-CSF treatment aggravates vascular remodeling of injured artery after
      acute myocardial infarction. Sprague-Dawley rats received transplanted bone
      marrow cells from green fluorescent protein (GFP) transgenic rats. Acute
      myocardial infarction was induced by ligation of the left coronary artery. After
      24 h, the right carotid artery was injured with a balloon catheter. G-CSF (100
      microg/kg/day) or saline was injected subcutaneously for 5 consecutive days after
      induction of acute myocardial infarction. G-CSF treatment significantly improved
      left ventricle function and reduced infarct size in rats with acute myocardial
      infarction. Expression of mRNA for the angiogenic cytokines was significantly
      higher in the infarction border area in the G-CSF group than in the control
      group. The surviving cardiomyocytes in infarction area were more in the G-CSF
      group. GFP-positive cells were gathered in the infarction border area in both
      groups; G-CSF did not increase cardiac homing of GFP-positive bone marrow cells
      in contrast to control group. Most GFP-positive cells were CD68-positive
      (macrophages). It was difficult to find bone marrow-derived cardiomyocytes in the
      infarcted area. G-CSF treatment inhibited neointima formation and increased
      reendothelialization of the injured artery. GFP-positive cells were identified
      most in the adventitia of the injured artery. A few cells in the neointima and
      reendothelialization were GFP positive. In conclusion, administration of G-CSF
      appears to be effective for treatment of left ventricular remodeling after acute
      myocardial infarction and does not aggravate vascular remodeling. The effect of G
      CSF on cardiac and vascular remodeling may occur mainly through a direct action
      on the heart and arteries.

PMID- 16979159
TI  - Involvement of Ca2+-independent phospholipase A2 in the translocation of hypoxia
      inducible factor-1alpha to the nucleus under hypoxic conditions.
AB  - We investigated the role of Ca2+-independent phospholipase A2 (iPLA2) as well as
      cytosolic phospholipase A2 (cPLA2) in hypoxia-inducible factor-1 (HIF-1)
      dependent gene expression. An inhibitor of both iPLA2 and cPLA2, methyl
      arachidonyl fluorophosphonate (MAFP), prevented hypoxia-induced erythropoietin
      mRNA expression without affecting HIF-1alpha accumulation in Hep3B cells. The DNA
      binding of HIF-1alpha was suppressed by MAFP as confirmed by luciferase reporter
      gene assays with the hypoxia response element. Translocation of HIF-1alpha to the
      nucleus assessed by its presence in the nuclear extracts of cells exposed to
      hypoxia, was diminished by MAFP. However, hypoxia-dependent gene expression was
      not affected in mesangial cells obtained from cPLA2alpha null mice. Furthermore,
      a specific iPLA2 inhibitor, bromoenol lactone, suppressed erythropoietin mRNA
      expression and HIF-1alpha translocation to the nucleus under hypoxic conditions.
      Thus, iPLA2, but not cPLA2alpha, may play an important role in regulating the
      transport of HIF-1alpha to the nucleus.

PMID- 16979160
TI  - Differential effects of methamphetamine and cocaine on behavior and extracellular
      levels of dopamine and 3,4-dihydroxyphenylalanine in the nucleus accumbens of
      conscious rats.
AB  - The central dopamine system plays a prominent role in the effect of
      psychostimulants such as methamphetamine, cocaine and nicotine. l-3,4
      Dihydroxyphenylalanine (DOPA), a precursor of dopamine, has been proposed as a
      neurotransmitter in the central nervous system. We have studied the effects of
      these psychostimulants on the release of DOPA and dopamine from the nucleus
      accumbens shell in conscious rats using in vivo microdialysis. Methamphetamine
      and cocaine increase the extracellular levels of dopamine. The effect of
      methamphetamine (1 mg/kg s.c.) on the release of dopamine was almost comparable
      to that of cocaine (10 mg/kg i.p.). However, methamphetamine increases, but
      cocaine decreases the extracellular levels of DOPA. In a behavioral study,
      methamphetamine (1 mg/kg s.c.) induced chewing, walking and sniffing behavior.
      Cocaine (10 mg/kg i.p.) produces weak effects on these behavioral parameters,
      when compared to the effects of methamphetamine (1 mg/kg s.c.). The behavioral
      changes produced by methamphetamine are suppressed by DOPA cyclohexyl ester (30
      mg/kg i.p.), a competitive DOPA antagonist. Endogenous DOPA in the nucleus
      accumbens thus appears to be in involved in the behavioral responses to these
      psychomotor stimulants.

PMID- 16979161
TI  - The direct antioxidative and anti-inflammatory effects of peroxisome proliferator
      activated receptors ligands are associated with the inhibition of angiotensin
      converting enzyme expression in streptozotocin-induced diabetic rat aorta.
AB  - Peroxisome proliferator-activated receptors (PPARs) are expressed on vascular
      tissue. To investigate the direct vasoprotective effects of PPARgamma and
      PPARalpha ligands, pioglitazone (3 mg/kg/day) and bezafibrate (10 mg/kg/day) were
      given by gavage to streptozotocin-induced diabetic rats for 4 weeks.
      Streptozotocin (65 mg/kg, i.p.) significantly increased NADPH oxidase, vascular
      call adhesion molecule-1 (VCAM-1), and osteopontin mRNA levels in the aorta, as
      determined by reverse transcription (RT)-polymerase chain reaction (PCR).
      Immunohistochemical analysis revealed that the expression of osteopontin protein
      was also enhanced in the streptozotocin-injected rat aorta. Pioglitazone or
      bezafibrate attenuated the streptozotocin-induced increase in the expression of
      NADPH oxidase and VCAM-1 mRNA. The enhanced expression of osteopontin gene and
      protein induced by streptozotocin was suppressed by pioglitazone, whereas
      treatment with bezafibrate had no effect on the expression of osteopontin. We
      also demonstrated that pioglitazone or bezafibrate prevented the streptozotocin
      induced increase in angiotensin converting enzyme (ACE) gene and protein content,
      by the means of RT-PCR and Western blotting. On the other hand, the treatment of
      pioglitazone or bezafibrate in the present study did not affect glucose
      tolerance, serum insulin or lipid level in streptozotocin-induced diabetic rats.
      These results suggest that the direct anti-oxidant and anti-inflammatory effects
      of PPARs ligands in the aorta of streptozotocin-induced diabetic rats were not
      likely to have been mediated by the normalization of glucose or lipid metabolism,
      but instead these salutary effects appear to have been associated with the
      inhibition of the expression of ACE. In addition, pioglitazone appeared to be
      more effective on the suppression of osteopontin expression compared with
      bezafibrate.

PMID- 16979162
TI  - Combined effect of probucol and insulin on renal damage in diabetic rats fed a
      high cholesterol diet.
AB  - We investigated the effects of long-term treatment with probucol, a hypolipidemic
      agent with antioxidative action, insulin, or their combination on renal damage in
      streptozotocin-induced diabetic rats fed a high cholesterol diet. Increases in
      urinary albumin and lipid peroxide excretions were observed in these diabetic
      rats, when both urinary parameters were measured at 8 and 15 weeks after
      streptozotocin administration. Daily treatment with probucol, insulin, or their
      combination markedly suppressed the increase in the 24 h urinary albumin and
      lipid peroxide excretions. Furthermore, glycogen degeneration of distal tubules,
      fatty degeneration of glomerular endothelium, and hypertrophy of glomeruli and
      mesangium were observed in the kidneys of the diabetic animals, when
      histopathological evaluation was performed at 4, 8 and 15 weeks (glomerular and
      mesangial hypertrophy was observed only at 15 weeks). Combined probucol and
      insulin treatment was the most effective in suppressing these renal
      histopathological changes. These results indicate that combined treatment with
      probucol and insulin is useful in preventing the progression of renal damage in
      diabetic rats. The possible mechanisms for the preventive effect of this combined
      treatment will be discussed.

PMID- 16979163
TI  - Cell signaling pathways to alphaB-crystallin following stresses of the
      cytoskeleton.
AB  - Small heat shock proteins (sHSPs) act as chaperone, but also in protecting the
      different cytoskeletal components. Recent results suggest that alphaB-crystallin,
      a member of sHSPs family, might regulate actin filament dynamics, stabilize them
      in a phosphorylation dependent manner, and protect the integrity of intermediate
      filaments (IF) against extracellular stress. We demonstrate that vinblastin and
      cytochalasin D, which respectively disorganize microtubules and actin
      microfilaments, trigger the activation of the p38/MAPKAP2 kinase pathway and lead
      to the specific alphaB-crystallin phosphorylation at serine 59. Upstream of p38,
      we found that RhoK, PKC and PKA are selectively involved in the activation of p38
      and phosphorylation of alphaB-crystallin, depending on the cytoskeletal network
      disorganized. Moreover, we demonstrate that chronic perturbations of IF network
      result in the same activation of p38 MAPK and alphaB-crystallin phosphorylation,
      as with severe disorganization of other cytoskeletal networks. Finally, we also
      show that Ser 59 phosphorylated alphaB-crystallin colocalizes with cytoskeletal
      components. Thus, disturbance of cytoskeleton leads by converging signaling
      pathways to the phosphorylation of alphaB-crystallin, which probably acts as a
      protective effector of the cytoskeleton.

PMID- 16979164
TI  - Low-density lipoprotein receptor-related protein-1 (LRP-1) expression in a rat
      model of oxygen-induced retinal neovascularization.
AB  - The low-density lipoprotein receptor-related protein-1 (LRP-1) is a high
      molecular weight receptor of the LDL receptor gene family. Its ability to bind
      and internalize both proteinases and proteinase-inhibitor complexes from the
      extracellular space suggests that it has a major role in modulating uncontrolled
      retinal cell proliferation. In order to test this assumption, we investigated the
      expression of LRP-1 and receptor-associated ligands in a rat model of oxygen
      induced retinal neovascularization. Wistar albino rats were placed into
      incubators at birth and exposed to an atmosphere alternating between 50% and 10%
      of oxygen every 24 h. After 14 days, the animals were allowed to recover in room
      air and sacrificed at postnatal day 20 (P20). The protein expression of LRP-1 and
      alpha2-macroglobulin (alpha2M) in the retina from unexposed and hyperoxia-exposed
      rats was investigated by Western blot. The localization of LRP-1 after
      neovascularization was assessed by immunohistochemical staining. The activity of
      metalloproteinases (MMPs) was determined by zymography. Histological analysis was
      done to quantitate the neovascular response in these animals. Western blot
      analysis showed that LRP-1 was expressed, along with alpha2M, in the retina of
      rats with oxygen-induced neovascularization at P20. By immunohistochemical
      analysis, positive staining for LRP-1 appeared in cells extending from the inner
      limiting membrane (ILM) to the outer limiting membrane (OLM). The cells of the
      retina that expressed LRP-1 were identified by immunofluorescence as Muller
      cells. Zymographic analysis demonstrated increased activity of MMP-2 and MMP-9
      under neovascular conditions. This is the first demonstration of the involvement
      of LRP-1 in retinal neovascularization. In retinas of rats with oxygen-induced
      neovascularization, the expression of LRP-1 and alpha2M was increased along with
      an enhanced activity of MMPs, suggesting that LRP-1 expression may play a role in
      modulating retinal neovascularization by regulating proteolytic activity.

PMID- 16979165
TI  - Leishmania major: immune response in BALB/c mice immunized with stress-inducible
      protein 1 encapsulated in liposomes.
AB  - Protection against leishmaniasis is depending upon generation of a Th1 type of
      immune response. Field trials of first generation Leishmania vaccine showed a
      limited efficacy even with multiple doses mainly due to lack of an appropriate
      adjuvant. In this study, susceptible BALB/c mice were immunized with rLmSTI1
      encapsulated in liposomes to explore the extent of protection induced by
      Leishmania antigen encapsulated in the liposomes against challenge with
      Leishmania major. The results showed that s.c. immunization of BALB/c mice with
      liposomal rLmSTI1 induced a significant protection against challenge and a
      significant lower parasite burden in spleen up to 14 weeks after challenge. The
      protected animals showed a significantly smaller footpad thickness after
      challenge, and a higher level of anti-SLA IgG antibodies before and after
      challenge with a predominant IgG2a titer. The data supports the possibility of
      using liposomal Leishmania antigens as a vaccine.

PMID- 16979167
TI  - Drug-induced phospholipidosis.
AB  - Drug-induced phospholipidosis is characterized by intracellular accumulation of
      phospholipids with lamellar bodies, most likely from an impaired phospholipid
      metabolism of the lysosome. Organs affected by phospholipidosis exhibit
      inflammatory reactions and histopathological changes. Despite significant
      advances in the understanding of drug-altered lipid metabolism, the relationship
      between impaired phospholipid metabolism and drug-induced toxicity remains
      enigmatic. Here we review molecular features of inheritable lysosomal storage
      disorders as a molecular mimicry of drug-induced phospholipidosis for an improved
      understanding of adverse drug reaction.

PMID- 16979166
TI  - Caveolin-1 controls BRCA1 gene expression and cellular localization in human
      breast cancer cells.
AB  - The role of caveolae and the caveolin proteins in cancer has been the subject of
      extensive research. BRCA1 participates in multiple biological pathways including
      DNA damage repair, transcriptional control, cell growth, apoptosis, and others.
      Little information, however, is available regarding the cellular mechanisms that
      control BRCA1 gene expression. The present study examined the potential
      regulation of BRCA1 gene expression and subcellular localization by Cav-1.
      Results of Western blots, RT-PCR, and transfection experiments showed that Cav-1
      enhances BRCA1 protein and mRNA levels via a mechanism that involves
      transactivation of the BRCA1 promoter and which is p53-dependent. In addition,
      immunostaining experiments demonstrate that Cav-1 induced the cytoplasmic
      sequestration of BRCA1.

PMID- 16979170
TI  - Minimally invasive ilioinguinal approach to the acetabulum.
AB  - The classic ilioinguinal approach is a gold standard in acetabular surgery. We
      developed a modification, a minimally invasive method that entails a median lower
      abdominal approach with extraperitoneal dissection and exposure of the pubic
      symphysis. The second incision is lateral, next to the iliac crest. This allows
      an easy, safe and quick exposure of the anterior iliac ring as well as easy
      access to the posterior column and wall towards the sacroiliac joint. The iliac
      vessels and nerves are thereby protected, and no preparation of neurovascular
      structures is required. The technique was applied in 23 clinical cases and
      compared with the classic ilioinguinal approach in 9 similar cases over the same
      period.

PMID- 16979168
TI  - Huntingtin-interacting protein 1-mediated neuronal cell death occurs through
      intrinsic apoptotic pathways and mitochondrial alterations.
AB  - Huntingtin interacting protein-1 (Hip1) is known to be associated with the N
      terminal domain of huntingtin. Although Hip1 can induce apoptosis, the exact
      upstream signal transduction pathways have not been clarified yet. In the present
      study, we examined whether activation of intrinsic and/or extrinsic apoptotic
      pathways occurs during Hip1-mediated neuronal cell death. Overexpression of Hip1
      induced cell death through caspase-3 activation in immortalized hippocampal
      neuroprogenitor cells. Interestingly, proteolytic processing of Hip1 into partial
      fragments was observed in response to Hip1 transfection and apoptosis-inducing
      drugs. Moreover, Hip1 was found to directly bind to and activate caspase-9. This
      promoted cytosolic release of cytochrome c and apoptosis-inducing factor via
      mitochondrial membrane perturbation. Furthermore, Hip1 could directly bind to
      Apaf-1, suggesting that the neurotoxic signals of Hip1 transmit through the
      intrinsic mitochondrial apoptotic pathways and the formation of apoptosome
      complex.

PMID- 16979171
TI  - Orthopaedic trauma workload in the former homeland of the Transkei, South Africa.
AB  - The Bedford Orthopaedic Centre is situated in Umtata at the heart of the former
      homeland of the Transkei in the Eastern Cape of South Africa. It acts as an
      orthopaedic and trauma referral hospital for a mainly rural population
      approaching 4 million. This article focuses on the workload of the hospital over
      a 4-month period and like many hospitals in South Africa we highlight the
      difficulties it faces with the trauma epidemic.

PMID- 16979172
TI  - Women's and providers' experiences of breech presentation in Jamaica: a
      qualitative study.
AB  - BACKGROUND: Most research on breech relates to medical management of the
      malpresentation. Little is known about women's or providers' experiences of
      breech, an obstetrical complication. OBJECTIVES: This study aims to increase the
      understanding of women's and providers' experiences of breech presentation and to
      understand the effects of context on these experiences. METHODS: A qualitative
      descriptive research was conducted in a rural health district of Jamaica. Nine
      postpartum women who birthed singleton live born breech infants in the past year
      and five experienced obstetric care providers consented to participate. Content
      analysis was conducted with data from one-time interviews, observations, and hand
      searches of maternity ward delivery logs. Member checking was conducted with
      successive participants and Jamaican health care providers. RESULTS: Findings
      included realizing the baby was breech, interpreting what breech meant, reacting
      to breech presentation, and identifying the impact of breech. Rates of breech
      births were less than 1%. CONCLUSIONS: Symbolic interaction can guide nursing and
      midwifery education, practice and research of breech presentation. Nurses and
      midwives can identify and teach women and their significant others about breech
      and its risks.

PMID- 16979173
TI  - Advocacy at end-of-life research design: an ethnographic study of an ICU.
AB  - BACKGROUND: Clinicians worldwide are being called upon to reconcile
      accountability for patient outcomes with the resources they consume. In the case
      of intensive care, contradictory pressures can arise in decisions about
      continuing treatment where benefit is diminishing. As concern grows about the
      cost effectiveness of treatment at end-of-life, nursing expertise and advocacy
      become significant factors in decision making. OBJECTIVES: To explore the
      potential for a nursing advocacy role within a specific regime of nursing
      practice: end-of-life care; specifically to examine the concept of nursing
      advocacy from the literature, to consider its application in the workplace and to
      assess the capacity for nurses to advocate for people who die in institutions
      such as intensive care units. DESIGN: Open-ended interviews with nurse managers
      and educators (4), palliative care specialists (2), chaplain (1), medical
      managers (2), intensives (7); focus groups with nurses (4 focus groups and 29
      participants); patient case studies (13); observation of family conferences (6
      conferences and 15 participants); observation of ward rounds (3 ward rounds and
      11 participants). Total number of participants: 84. SETTING: A large ICU in a
      principal referral and teaching hospital in Sydney, Australia. PARTICIPANTS:
      Clinical staff within, and clinical and non-clinical caregivers external to the
      unit. METHOD: Qualitative, ethnographic study. RESULTS: Spurious economic
      imperatives, primacy given to medical intervention, conflict between medical and
      nursing clinicians about patient management and absence of nursing operational
      autonomy and organizational authority, impede the opportunity for nurses to
      define and enact an advocacy role. CONCLUSIONS: If nurses are to be effective
      patient advocates at end-of-life, they will need to develop clear criteria within
      which nursing assessments of patient status can be framed, the specialized skills
      to manage the non-medical needs of dying people and the organizational and
      political skills to negotiate changing clinical practice and workplace relations.

PMID- 16979174
TI  - Diabetic atherosclerosis mouse models.
AB  - Coronary heart disease (CHD) due to atherosclerosis is the leading cause of death
      in the USA, and accelerated CHD has emerged as a leading cause of morbidity and
      mortality in diabetic patients in the USA and worldwide. This has highlighted the
      importance and urgency of studying the mechanism of diabetic atherosclerosis and
      exploring therapeutic options. Due to its unique advantages over other animal
      models, the mouse is the most used model for studying the mechanism of diabetes
      accelerated atherosclerosis and exploring effective therapeutic approaches. In
      the past decade, several diabetic atherosclerosis mouse models have been
      established. Currently, however, there is no ideal animal model for diabetic
      atherosclerosis. To determine the characteristics of the models that more closely
      resemble human diabetic atherosclerosis disease, this review focuses on the
      common diabetic atherosclerosis mouse models with respect to the following
      issues: (1) whether the mice retain diabetic condition; (2) whether the diabetes
      accelerates atherosclerosis or increases atherogenic inflammation; (3) whether
      these factors respond to medical interventions. The discussion is aimed at
      identifying different diabetic mouse models and their features, in order to
      heighten awareness of the appropriate models that may provide useful tools for
      studying the mechanism of diabetes-accelerated atherosclerosis and evaluating
      therapeutic options.

PMID- 16979175
TI  - Regarding the potential perils of phytosterols.

PMID- 16979176
TI  - Metabolic syndrome as a risk factor for coronary heart disease and stroke: an 11
      year prospective cohort in Taiwan community.
AB  - OBJECTIVE: Patterns of metabolic syndrome among populations in the Asia-Pacific
      region remain unknown. This study sought to establish the prevalence of metabolic
      syndrome in Taiwan and the risk of cardiovascular disease imparted by this
      syndrome. METHODS AND RESULTS: A cohort of 3602 individuals aged 35 years and
      above from one Taiwan community in 1990-1991 was followed up for a median of 9.0
      years (inter-quartile range: 7.9-10.0 years). Women had a higher prevalence rates
      of age-standardized metabolic syndrome than men (28.9% versus 16.6%) by original
      NCEP-ATP III criteria, and the rates increased progressively. As numbers of
      metabolic syndrome increased, the hazard risk (HR) increased significantly, up to
      5.5 (95% confidence interval [CI], 2.2-13.7) for coronary heart disease and 3.5
      (95% CI, 1.9-6.5) for stroke. We found that low HDL cholesterol and high BMI had
      the highest risk for coronary heart disease (HR, 2.3), followed by metabolic
      syndrome (HR, 1.8). For stroke events, high blood pressure had the highest risk
      (HR, 3.0), also followed by metabolic syndrome (HR, 2.1). The highest
      attributable risk for the general population was low HDL cholesterol for coronary
      heart disease event and high blood pressure for stroke. CONCLUSIONS: Metabolic
      syndrome was highly prevalent among the adult population and associated with an
      increased risk for coronary heart disease and stroke.

PMID- 16979177
TI  - Simultaneous determination of benserazide and levodopa by capillary
      electrophoresis-chemiluminescence using an improved interface.
AB  - A capillary electrophoresis coupling with indirect chemiluminescence detection
      method for the simultaneous determination of benserazide and levodopa has been
      developed. The detection interface was improved to simplify the capillary
      electrophoresis-chemiluminescence (CE-CL) system and the features of this
      improved interface were illustrated in this paper. The CE-CL conditions for the
      simultaneous determination of benserazide and levodopa were optimized. Under the
      optimal conditions, the CL intensity was linear with concentrations of levodopa
      in the range of 1.0 to 100.0 microg ml(-1), and benserazide in the range of 10.0
      to 1,000 microg ml(-1), respectively. The detection limits (S/N=3) in turn were
      1.85 microg ml(-1) for BS and 0.12 microg ml(-1) for L-dopa with relative
      standard deviations of less than 3%. The proposed method has been successfully
      applied to the determination of benserazide and levodopa in medopar tablets and
      spiked urine samples, demonstrating the feasibility and reliability of the
      proposed method.

PMID- 16979178
TI  - The role of capillary and surface forces in the crossover behavior of solid
      nanoparticles at liquid interfaces.
AB  - We investigate the interaction between a nanoparticle and an oil-water interface
      with particular emphasis on the particle crossing through the interface. The
      formation of a three-phase contact line is investigated in two cases, namely in
      the presence and in the absence of surface forces. We carefully examine the
      interplay between capillary and surface forces in such systems. Two instabilities
      of the interface (snap-in/snap-out) as the particle is moved through the
      interface are identified and quantitatively described. While the snap-in
      instability was observed in some AFM studies, the precise interface position and
      configuration relative to the particle at the instability depends on the nature
      of the surface forces present in the system. After the snap-in, the particle is
      adsorbed and must overcome an energy barrier due to the interface deformation in
      order to cross-over to the other liquid. We make quantitative predictions on the
      interface configuration at the instabilities and the free energy barrier height.
      The roles of particle size and different interaction parameters characterizing
      the system in determining the magnitude of the energy barrier for crossing and in
      the formation of a three-phase contact line are discussed. Ultimately, this study
      will enable us to make quantitative predictions on capillary effects in
      nanoparticle-microemulsions mixtures and other colloidal systems. For particles
      in the micrometer range and larger the capillary forces dominate over the surface
      forces and dictate how the snap-in occurs. However, the situation becomes
      different for particle sizes smaller than about 100 nm. The presence of surface
      forces modifies the interface configuration and the free energy jump at the snap
      in instability.

PMID- 16979179
TI  - Role of solvation forces in the gelation of fumed silica-alcohol suspensions.
AB  - Aggregation and gelation kinetics of fumed silica were investigated by altering
      the solvent-surface interactions. Native and surface-modified (hydrophobic) fumed
      silica particles were dispersed in short-chain linear alcohols. Based on the
      kinetics of aggregation and gelation, we show that the solvent-surface
      interactions have a tremendous impact on the bulk suspension properties. The
      gelation kinetics were qualitatively similar in all of the fumed silica-alcohol
      samples, and the gel times for all the alcohols were captured on a master curve
      requiring two parameters. The two parameters, the stability ratio and critical
      volume fraction, describe the two regimes of gelation. At low concentrations,
      gelation occurs due to aggregation of the particles diffusing over a potential
      barrier (15-25 kT). The rate of aggregation and time to gelation then scales with
      the stability ratio. At high particle loadings, gelation occurs at a critical
      volume fraction due to localization in a secondary minimum with a depth of 3-4
      kT. These observations are supported by evidence of hydrogen bonding between the
      solvent and the particle, creating oscillatory solvation forces that govern the
      magnitude of these two parameters.

PMID- 16979180
TI  - Turbulent inertial gelation and acoustic quasi-gelation of submicron aerosol
      particles.
AB  - Inertial turbulent and acoustic orthokinetic particle coagulation mechanisms have
      physical similarity. We consider analytically and numerically coagulation of
      discrete compact and fractal submicron agglomerated particles, governed by these
      mechanisms via Smoluchowski equation. Existence of the inertial turbulent
      coagulation is mathematically proven. A new gelation scenario is revealed for
      both of the above coagulation mechanisms. Turbulent inertial gelation is
      manifested by means of a multi-modal relay-type run-away particle size growth,
      including formation of infinite set of secondary maxima in volume fraction
      distribution. When acoustic coagulation mechanism is much stronger than the
      Brownian coagulation, acoustic coagulation occurs as a quasi-gelation process,
      with a run-away particle size growth, characterized, however, by a finite set of
      secondary maxima. The effect of acoustic field on coagulation is shown to be more
      pronounced for fractal agglomerates than that for compact agglomerated particles.

PMID- 16979181
TI  - Quantification of mannan-binding lectin.
AB  - Mannan-binding lectin (MBL) is attracting considerable interest due to its role
      in the immune defense. The high frequency of congenital MBL deficiency makes it
      feasible to evaluate clinical relevance through epidemiological investigations on
      fairly limited numbers of patients. MBL deficiency is determined by three mutant
      allotypes termed B, C and D in the coding region as well as mutations in the
      promoter region. It has been suggested that individuals, with deficiency
      associated allotypes, may present significant amounts of low molecular weight
      MBL. We have compared the quantification of MBL by four commercially available
      assays with results obtained by our own in-house assays. Most assays are
      selectively sensitive for the wild type MBL (allotype A), but special
      combinations of antibodies also detect mutant forms of MBL. Thus a sandwich-type
      time-resolved immunoflourometric assay (TRIFMA), with a mouse monoclonal antibody
      (93C) as the catching and detecting antibody, shows B/B and D/D homozygous
      individuals to present signals corresponding to up to 500 ng MBL per ml (with
      plasma from an A/A individual as standard) as compared to less than 50 ng/ml and
      200 ng/ml, respectively, when measured in other assays. In GPC at isotonic
      conditions the MBL in B/B and D/D individuals showed a Mr of 450 kDa. This MBL
      cannot bind to mannan. We further present a new method for quantifying the amount
      of MBL polypeptide chain. By applying plasma samples on SDS-PAGE at reducing
      conditions followed by Western blotting and quantification by chemiluminescense,
      this approach presents single polypeptide chains to the antibody independent of
      allotype differences in the collagen-like region. Titrations of recombinant MBL
      served as standard. In sera from homozygous mutants (O/O) the MBL concentrations
      estimated on Western blot were in the range of 100 to 500 ng/ml and correlated
      with that measured in the 93C-based TRIFMA.

PMID- 16979182
TI  - Angiotensin II, oxidative stress, and extracellular matrix degradation during
      transition to LV failure in rats with hypertension.
AB  - Angiotensin II (Ang-II) plays pivotal roles in the progression of left
      ventricular (LV) remodeling in diseased hearts; it remains to be elucidated how
      Ang-II links to degradation of the extracellular matrix (ECM). Using hypertensive
      Dahl salt-sensitive rats that show the distinctive transition from concentric LV
      hypertrophy to LV remodeling, we chronically treated them with an angiotensin
      type-1 receptor blocker (telmisartan 5 mg/kg/day, ARB group) or vehicle (0.5%
      CMC, CHF group). During the process of LV remodeling, we assessed, (1) in-vivo LV
      shape and function; (2) animal survival; (3) amounts of ECM in LV using a
      scanning electron microscope (SEM); (4) mRNA (by real time RT-PCR) and protein
      (by immunoblotting) levels in LV of NADPH oxidase, glutathione peroxidase-1 (GPX
      1), and matrix metalloproteinase (MMP)-2, -9, and -13; (5) immunohistochemical
      staining of myocardial 4-hydroxy-2-nonenal and 8-hydroxy-2'-deoxyguanosine; (6)
      nuclear factor kappa-B (NFkappaB) protein levels in the nuclear extract; and (7)
      endogenous activities of MMP-2 and -9 by an antibody capture method. Compared
      with CHF, ARB group showed an improvement of survival and preserved LV shape and
      function, and ECM density in SEM that was accompanied by decreases in oxidative
      stress-mediated protein degenerations, activities of GPX-1, NADPH oxidase,
      NFkappaB, and MMP-2, -9, and -13. Local activation of Ang-II in hypertrophic LV
      triggers MMP-mediated ECM degradation, namely LV remodeling, at least in part,
      through NADPH oxidase-induced oxidative stress and the subsequent NFkappaB
      activation.

PMID- 16979183
TI  - Chain length-dependent binding of fatty acid anions to human serum albumin
      studied by site-directed mutagenesis.
AB  - Human serum albumin is the most abundant protein in the circulatory system, and
      one of its principal functions is to transport fatty acids. Binding of octanoate,
      decanoate, laurate and myristate was studied by a rate-of-dialysis technique. The
      primary association constants increased, but not linearly, with chain length. The
      number of high-affinity sites also increased with chain length; octanoate and
      decanoate bind to one such site, whereas laurate and myristate most probably bind
      to two sites. Albumin is composed of three homologous helical domains (I-III),
      which can be subdivided into two subdomains (A and B). For getting information
      about the positions of the high-affinity sites we produced 13 recombinant
      isoforms mutated in four different subdomains. Results obtained with these
      albumins are in accordance with the following model: octanoate and decanoate bind
      to a single site in subdomain IIIA, laurate binds to sites in subdomains IIIA and
      IIIB, whereas myristate binds in subdomains IB and IIIB. The results also showed
      that primary fatty acid binding is sensitive to amino acid substitutions in other
      parts of the protein. This is in contrast to the effect of amino acid
      substitutions of genetic albumin variants (alloalbumins). Usually these
      substitutions, which are situated at the surface of the protein, have no effect
      on fatty acid binding. Binding of fatty acid anions to different high-affinity
      sites and the sensitivity of these sites to amino acid substitutions elsewhere in
      the protein (and perhaps also to other types of modifications) are important
      factors that could effect simultaneous binding of other ligands, e.g. in patients
      treated with albumin-binding drugs.

PMID- 16979184
TI  - Requirement of tryptophan hydroxylase during development for maturation of
      sensorimotor gating.
AB  - Deficits in sensorimotor gating, a function to focus on the most salient
      stimulus, could lead to a breakdown of cognitive integrity, and could reflect the
      "flooding" by sensory overload and cognitive fragmentation seen in schizophrenia.
      Sensorimotor gating emerges at infancy, and matures during childhood. The
      mechanisms that underlie its development are largely unclear. Here, we screened
      the mouse genome, and found that tryptophan hydroxylase (TPH) is implicated in
      the maturation of sensorimotor gating. TPH, an enzyme involved in the
      biosynthesis of serotonin, proved to be required only during the weaning period
      for maturation of sensorimotor gating, but was dispensable for its emergence.
      Proper serotonin levels during development underlie the mature functional
      architecture for sensorimotor gating via appropriate actin polymerization. Thus,
      maintaining proper serotonin levels during childhood may be important for mature
      sensorimotor gating in adulthood.

PMID- 16979185
TI  - Structure of an AAGU tetraloop and its contribution to substrate selection by
      yeast RNase III.
AB  - RNase III enzymes are a highly conserved family of proteins that specifically
      cleave double-stranded RNA (dsRNA). These proteins are involved in a variety of
      cellular functions, including the processing of many non-coding RNAs, mRNA decay,
      and RNA interference. In yeast Rnt1p, a dsRNA-binding domain (dsRBD) recognizes
      its substrate by interacting with stems capped with conserved AGNN tetraloops.
      The enzyme uses the tetraloop to cut 14nt to 16nt away into the stem in a ruler
      like mechanism. The solution structure of Rnt1p dsRBD complexed to one of its
      small nucleolar (sno) RNA substrate revealed non-sequence-specific contacts with
      the sugar-phosphate backbone in the minor groove of the AGNN fold and the two non
      conserved tetraloop nucleotides. Recently, a new form of Rnt1p substrates lacking
      the conserved AGNN sequence but instead harboring an AAGU tetraloop was found at
      the 5' end of snoRNA 48 precursor. Here, we report the solution structure of this
      hairpin capped with an AAGU tetraloop. Some of the stacking interactions and the
      position of the turn in the sugar-phosphate backbone are similar to the one
      observed in the AGNN loop structure; however, the AAGU sequence adopts a
      different conformation. The most striking difference was found at the 3' end of
      the loop where Rnt1p interacts with AGNN substrates. The last nucleotide is
      extruded from the AAGU tetraloop structure in contrast to the compact AGNN fold.
      The AAGU hairpin structure suggests that Rnt1p recognizes substrates with
      different tetraloop structures, indicating that the structural repertoire
      specifically recognized by Rnt1p is larger than previously anticipated.

PMID- 16979186
TI  - PARP-1 interaction with VP1 capsid protein regulates polyomavirus early gene
      expression.
AB  - Poly(ADP-ribose)polymerases are involved in fundamental cellular events as well
      as they seem to be associated to some viral infection process. In this work, the
      poly(ADP-ribose)polymerase-1 (PARP-1) role in the polyomavirus life cycle has
      been investigated. Early viral transcription was reduced by competitive
      inhibitors of PARPs in Swiss 3T3 cells and almost abolished in PARP-1 knockout
      fibroblasts and in wild-type fibroblasts when PARP-1 was silenced by RNA
      interference. In vivo chromatin immunoprecipitation assays showed that poly(ADP
      ribosyl)ation (poly(ADP-ribose)) facilitates the release of the capsid protein
      viral protein 1 (VP1) from the chromatin of infecting virions. In vitro
      experiments demonstrated that VP1 stimulates the enzymatic activity of PARP-1 and
      binds non-covalently both protein-free and PARP-1-bound poly(ADP-ribose). Our
      studies suggest that PARP-1 promotes the complete VP1 displacement from viral DNA
      favouring the viral early transcription.

PMID- 16979187
TI  - Evolutionally conserved intermediates between ubiquitin and NEDD8.
AB  - The investigation of common structural motifs provides additional information on
      why proteins conserve similar topologies yet may have non-conserved amino acid
      sequences. Proteins containing the ubiquitin superfold have similar topologies,
      although the sequence conservation is rather poor. Here, we present novel
      similarities and differences between the proteins ubiquitin and NEDD8. They have
      57% identical sequence, almost identical backbone topology and similar functional
      strategy, although their physiological functions are mutually different. Using
      variable pressure NMR spectroscopy, we found that the two proteins have similar
      conformational fluctuation in the evolutionary conserved enzyme-binding region
      and contain a structurally similar locally disordered conformer (I) in
      equilibrium with the basic folded conformer (N). A notable difference between the
      two proteins is that the equilibrium population of I is far greater for NEDD8
      (DeltaG(0)(NI)<5 kJ/mol) than for ubiquitin (DeltaG(0)(NI)=15.2(+/-1.0) kJ/mol),
      and that the tendency for overall unfolding (U) is also far higher for NEDD8
      (DeltaG(0)(NU)=11.0(+/-1.5) kJ/mol) than for ubiquitin (DeltaG(0)(NU)=31.3(+/
      4.7) kJ/mol). These results suggest that the marked differences in thermodynamic
      stabilities of the locally disordered conformer (I) and the overall unfolding
      species (U) are a key to determine the functional differences of the two
      structurally similar proteins in physiology.

PMID- 16979188
TI  - Hypothalamic-pituitary-adrenocortical (HPA) activity in kindergarten children:
      importance of gender and associations with behavioral/emotional difficulties.
AB  - The current cross-sectional study investigated basal and stress-challenged
      hypothalamic-pituitary-adrenocortical (HPA) system function in 102 five-year old
      kindergarten children (59 boys, 43 girls) who had been assessed by a
      comprehensive psychological and behavioral test battery. Baseline HPA system
      activity was significantly increased in girls when compared to boys (p<0.001).
      Furthermore, basal HPA system activity predicted a high hormonal release during
      stress with--again--girls showing higher hormonal responses than boys (p<0.01).
      Importantly, increased HPA system activity (baseline and stress-challenged) was
      significantly associated with hyperactivity/impulsivity and emotional problems in
      boys and with positive emotions in girls (p<0.05). These results suggest an
      occurrence of neurobiological alterations early in development. The observed
      neurobiological changes are gender specific already at the age of 5 years.
      Prospective long-term follow up of the identified subjects with HPA axis
      alterations will clarify if these markers are predictive for the onset of
      psychiatric disorders.

PMID- 16979189
TI  - Mate choice evolution, dominance effects, and the maintenance of genetic
      variation.
AB  - Female mate choice influences the maintenance of genetic variation by altering
      the mating success of males with different genotypes. The evolution of
      preferences themselves, on the other hand, depends on genetic variation present
      in the population. Few models have tracked this feedback between a choice gene
      and its effects on genetic variation, in particular when genes that determine
      offspring viability and attractiveness have dominance effects. Here we build a
      population genetic model that allows comparing the evolution of various choice
      rules in a single framework. We first consider preferences for good genes and
      show that focused preferences for homozygotes evolve more easily than broad
      preferences, which allow heterozygous males high mating success too. This occurs
      despite better maintenance of genetic diversity in the latter scenario, and we
      discuss why empirical findings of superior mating success of heterozygous males
      consequently do not immediately lead to a better understanding of the lek
      paradox. Our results thus suggest that the mechanisms that help maintain genetic
      diversity also have a flipside of making female choice an inaccurate means of
      producing the desired kind of offspring. We then consider preferences for
      heterozygosity per se, and show that these evolve only under very special
      conditions. Choice for compatible genotypes can evolve but its selective
      advantage diminishes quickly due to frequency-dependent selection. Finally, we
      show that our model reproduces earlier results on selfing, when the female choice
      strategy produces assortative mating. Overall, our model indicates that various
      forms of heterozygote-favouring (or variable) female choice pose a problem for
      the theory of sexual ornamentation based on indirect benefits, rather than a
      solution.

PMID- 16979190
TI  - Expression of isoforms of NADPH oxidase components in rat pancreatic islets.
AB  - Increased oxidative stress plays a role in the pathogenesis of beta-cell
      dysfunction and death. We studied isoforms of NADPH oxidase components in islets
      of Langerhans isolated from rat pancreas and tumoral rat beta-cell line RINm5F
      cells by RT-PCR and sequencing of its products. RT-PCR revealed that isolated
      islets constitutively expressed mRNA of NADPH oxidase components, Nox1, Nox2,
      Nox4 and p22(phox) as membrane-associated components and p47(phox), Noxo1
      (homologue of p47(phox)), Noxa1 (homologue of p67(phox)), and p40(phox) as
      cytosolic components. RINm5F cells showed a similar pattern of expression but
      Nox2 mRNA was not detected. Expression of Nox1, Nox4, Noxo1 and Noxa1 was
      confirmed by sequencing the PCR products. Immunohistochemistry revealed the
      expression of NADPH oxidase component in beta-cells of rat pancreatic islets.
      Glucose-stimulated insulin secretion from isolated islets was suppressed by
      diphenyleneiodonium, a flavocytochrome inhibitor, but not by apocynin, an
      inhibitor of p47(phox) translocation to membranes. Our results suggest that the
      functional significance of NADPH oxidase in insulin secretion may merit further
      investigation.

PMID- 16979191
TI  - Characterization of the transient receptor potential channels mediating
      lysophosphatidic acid-stimulated calcium mobilization in B lymphoblasts.
AB  - Altered 1-oleoyl-lysophosphatidic acid (LPA, 100 microM)-stimulated calcium
      responses occur in B-lymphoblast cell lines from bipolar disorder patients, but
      the mechanism(s) involved is uncertain. Lysophosphatidic acid shares a
      structurally similar fatty acid side chain with the diacylglycerol analogue, 1
      oleoyl-2-acetyl-sn-glycerol (OAG), a known activator of subtypes 3, 6 and 7 of
      the canonical transient receptor potential (TRPC) cation channel subfamily.
      Accordingly, the objective of this study was to determine whether the LPA
      stimulated calcium response in B-lymphoblasts is mediated, in part, through this
      TRPC channel subfamily. Divalent cation selectivity in response to thapsigargin,
      LPA and OAG were used to distinguish TRPC-like character of the responses to
      these agents in BLCLs. The sensitivity to gadolinium, an inhibitor of
      capacitative calcium channels, was used to determine the store-operated nature of
      the responses. The TRPC isoforms that are present in BLCLs as identified by
      immunoblotting and/or PCR include TRPC1, 3 and 5. Minimal barium influx in
      calcium-free buffer was observed following thapsigargin stimulation. However, LPA
      stimulated barium influx of a magnitude similar to that induced by OAG.
      Thapsigargin-provoked calcium influx was completely inhibited by gadolinium (10
      microM), whereas LPA and OAG-stimulated responses were partially inhibited and
      potentiated, respectively. The results suggest that 100 microM LPA stimulates
      calcium entry through channels with characteristics similar to TRPC3, as TRPC6
      and 7 are absent in B-lymphoblasts.

PMID- 16979192
TI  - Anthelmintic resistance: the state of play revisited.
AB  - Helminthosis is one of the major constraints in the successful wool and mutton
      industry throughout the world. Anthelmintic Resistance (AR) is said to have been
      established when previously effective drug ceases to kill exposed parasitic
      population at the therapeutically recommended dosages. Anthelmintic resistance is
      almost cosmopolitan in distribution and it has been reported in almost all
      species of domestic animals and even in some parasites of human beings. Some of
      the most important species of parasites of small ruminants in which AR has been
      reported include: Haemonchus spp., Trichostrongylus spp. Teladorsagia spp.,
      Cooperia spp. Nematodirus spp., and Oesophagostomum spp. All the major groups of
      anthelmintics have been reported for development of variable degrees of
      resistance in different species of gastrointestinal nematodes. This paper
      describes the global scenario of prevalence and methods used for detection of AR
      in small ruminants. Different mechanisms and contributory factors for the
      development of AR are discussed. Various options and alternate strategies for the
      control and/or delay in the onset of AR are suggested in the light of available
      information.

PMID- 16979194
TI  - Intraventricular insulin and leptin reduce food intake and body weight in
      C57BL/6J mice.
AB  - As the incidence of obesity continues to increase, adequate animal models acquire
      increased importance for the investigation of energy homeostatic mechanisms.
      Understanding the central mechanism of action of the adiposity hormones, insulin
      and leptin, has become particularly important as researchers examine ways to
      treat or prevent obesity. Although the intra-3rd-ventricular (i3vt)
      administration of insulin reduces food intake in several species, its effects on
      food intake and body weight have not been previously been assessed in mice. Male
      C57BL/6J mice were administered insulin i3vt (0.05, 0.1 or 0.4 microU) or leptin
      i3vt (5 microg/1 microl) as a positive control. As it occurs in other species,
      i3vt insulin dose-dependently reduced 24-h food intake and body weight, and
      increased hypothalamic proopiomelanocortin (POMC) mRNA. Hence, genetic
      manipulations that influence brain insulin sensitivity in mice can now more
      easily be integrated with the broader literature on energy homeostasis.

PMID- 16979195
TI  - Conclusion: where next?

PMID- 16979196
TI  - Public health, private right, and the common law.

PMID- 16979198
TI  - Health and human rights.

PMID- 16979200
TI  - Health policy and European law: closing the gaps.

PMID- 16979201
TI  - A study of the activity of 2-(alkylamino)-1-phenyl-1-ethanethiosulfuric acids
      against infection by Schistosoma mansoni in a murine model.
AB  - The schistosomicidal activities of seven 2-(alkylamino)-1-phenyl-1
      ethanethiosulfuric acids (1a-g) (R=propyl, isopropyl, butyl, isobutyl, t-butyl,
      sec-butyl, cyclohexyl, respectively) were determined in female Swiss mice
      infected with Schistosoma mansoni. The compounds were administered in a single
      oral dose of 800 mg/kg to groups of 15 mice infected with 50 cercariae each. All
      the compounds were found to be active, a high animal mortality being observed
      with 1e. These compounds have a high specificity against female worms (64-100%
      reduction vs. 33-61% reduction in male worms). The test was repeated, a 400-mg/kg
      sub-dose of 1f also being tested, and similar results were observed. A 94%
      reduction in the number of female worms was observed when compound 1c was
      administered in a single 800-mg/kg dose to animals infected with 80 cercariae.
      Finally, the test was repeated with single 800 mg/kg oral doses of compounds 1e
      (highly purified) and 1f and a 400-mg/kg sub-dose of 1c. The toxicity of 1e was
      confirmed, while the animals that received 1c and 1f presented reductions in the
      worm loads corresponding to 45.9% (male worms) and 84.8% (female worms) for 1c
      and 50.4% (male worms) and 94.2% (female worms) for 1f.

PMID- 16979202
TI  - Accuracy of the health information system on malaria surveillance in Vietnam.
AB  - The health information system (HIS) is a key component of control programs and
      its accuracy is necessary for the assessment of disease risks, the formulation of
      priorities and the evaluation of the cost-effectiveness of different
      interventions. In order to assess the quality of the HIS in estimating malaria
      morbidity in Vietnam, we compared data obtained by a 2-year active (ACD) and
      passive case detection (PCD) study with those routinely collected at the local
      commune health centres (CHC) at three sites having different malaria
      epidemiology. The majority of malaria cases (80-95%) detected by ACD were missed
      by the HIS. Similarly, most malaria cases (50-90%) detected by PCD were also
      missed by the HIS, and this was proportional to the number of active private
      practitioners. Reasons for this low sensitivity are low CHC attendance, high
      attendance at private health facilities, widespread self-medication and
      attendance at central health facilities. In conclusion, although malaria has
      sharply decreased in Vietnam over the past 10 years, the current HIS greatly
      underestimates the malaria burden. Involvement of the private sector and the
      establishment of sentinel sites might improve the quality of data and the
      relevance of HIS in malaria control.

PMID- 16979203
TI  - A self-similarity model for the occupancy frequency distribution.
AB  - The shapes of interspecific range-size distributions at scales finer than the
      geographic range are highly variable. However, no numerical model has been
      developed as a basis for understanding this variation. Using self-similarity
      conditions, we present an occupancy probability transition (OPT) model to
      investigate the effect of sampling scale (i.e. sample grain) and species
      saturation (strongly positively correlated with the fractal dimension) on the
      shape of occupancy frequency distributions (fine scale expression of range-size
      distributions). In accordance with empirical observations, the model showed that
      core-modes are likely to be rare in occupancy frequency distributions. The modal
      occupancy shifted from core to satellite with an increase in sample grain (from
      coarse scale to fine scale) at a linear rate after log-transformation of
      occupancy. Saturation coefficients above a particular threshold generated
      multimodality. Bimodal distributions arose from a combination of different
      occupancy probability distributions (OPDs), with species-specific saturation
      coefficients generating occupancy frequency distributions of the shape commonly
      observed empirically, i.e. bimodal with a dominant satellite mode. This is a
      consequence of the statistical properties of the OPD, and is also largely
      insensitive to species richness. The OPT model thus provides a null model for the
      shape of occupancy frequency distributions. Furthermore, it demonstrates that the
      sample grain of a study, sampling adequacy (based on a linear sampling
      assumption) and the distribution of species saturation coefficients in a
      community are together largely able to explain the patterns observed in empirical
      occupancy frequency distributions.

PMID- 16979204
TI  - Leflunomide or A77 1726 protect from acetaminophen-induced cell injury through
      inhibition of JNK-mediated mitochondrial permeability transition in immortalized
      human hepatocytes.
AB  - Leflunomide, a disease-modifying anti-rheumatic drug, protects against T-cell
      mediated liver injury by poorly understood mechanisms. The active metabolite of
      leflunomide, A77 1726 (teriflunomide) has been shown to inhibit stress-activated
      protein kinases (JNK pathway), which are key regulators of mitochondria-mediated
      cell death. Therefore, we hypothesized that leflunomide may protect from drugs
      that induce the mitochondrial permeability transition (mPT) by blocking the JNK
      signaling pathway. To this end, we exposed cultured immortalized human
      hepatocytes (HC-04) to the standard protoxicant drug acetaminophen (APAP), which
      induces CsA-sensitive mPT-mediated cell death. We determined the effects of
      leflunomide on the extent of APAP-induced hepatocyte injury and the upstream JNK
      mediated mitochondrial signaling pathways. We found that leflunomide or A77 1726
      concentration-dependently protected hepatocytes from APAP (1 mM)-induced
      mitochondrial permeabilization and lethal cell injury. This was not due to
      proximal inhibition of CYP-catalyzed APAP bioactivation to its thiol-reactive
      metabolite. Instead, we demonstrate that leflunomide (20 microM) inhibited the
      APAP-induced early (3 h) activation (phosphorylation) of JNK1/2, thus inhibiting
      phosphorylation of the anti-apoptotic protein Bcl-2 and preventing P-Bcl-2
      mediated induction of the mPT. This greatly attenuated mitochondrial cytochrome c
      release, which we used as a marker for mitochondrial permeabilization. The
      specific JNK2 inhibitor SP600125 similarly protected from APAP-induced cell
      death. In conclusion, these findings are consistent with our hypothesis that
      leflunomide protects from protoxicant-induced hepatocyte injury by inhibiting JNK
      signaling and preventing mPT induction.

PMID- 16979205
TI  - Role of IgG(T) and IgGa isotypes obtained from arachnidic antivenom to neutralize
      toxic activities of Loxosceles gaucho, Phoneutria nigriventer and Tityus
      serrulatus venoms.
AB  - The ability of IgG(T) and IgGa subclasses--isolated by liquid chromatography from
      equine arachnidic antivenom (AAV)-to neutralize toxic activities of Loxosceles
      gaucho, Phoneutria nigriventer and Tityus serrulatus venoms as well as to remove
      venom toxins from circulation was investigated. These subclasses showed similar
      antibody titers against L. gaucho, P. nigriventer and T. serrulatus venoms, and
      by immunoblotting few differences were observed in the recognition pattern of
      venom antigens. IgG(T) and IgGa neutralized 100% lethality induced by L. gaucho
      and 50% of P. nigriventer venom, but IgGa failed to neutralize T. serrulatus
      venom, in contrast to IgG(T). Both subclasses neutralized local reactions and
      dermonecrosis induced by L. gaucho venom in rabbits. In mice, IgG(T) and IgGa
      partially neutralized the edematogenic activity induced by P. nigriventer and T.
      serrulatus venoms, but only IgG(T) neutralized (ca. 81%) the nociceptive activity
      induced by T. serrulatus venom. Both subclasses failed to neutralize nociceptive
      activity induced by P. nigriventer venom. IgG(T) reduced the serum venom levels
      of animals injected with L. gaucho, P. nigriventer or T. serrulatus venoms, while
      IgGa solely reduced L. gaucho and P. nigriventer venoms levels. Our results
      demostrate that IgG(T) and IgGa subclasses neutralize toxic activities induced by
      P. nigriventer, T. serrulatus and L. gaucho venoms with different efficacies, as
      well as depurate these venoms from circulation.

PMID- 16979206
TI  - In vitro ultrasound-mediated leakage from phospholipid vesicles.
AB  - Interest in using ultrasound energy in wound management and intracellular drug
      delivery has been growing rapidly. Development and treatment optimization of such
      non-diagnostic applications requires a fundamental understanding of interactions
      between the acoustic wave and phospholipid membranes, be they cell membranes or
      liposome bilayers. This work investigates the changes in membrane permeation
      (leakage mimicking drug release) in vitro during exposure to ultrasound applied
      in two frequency ranges: "conventional" (1 MHz and 1.6 MHz) therapeutic
      ultrasound range and low (20 kHz) frequency range. Phospholipids vesicles were
      used as controllable biological membrane models. The membrane properties were
      modified by changes in vesicle dimensions and incorporation of poly(ethylene
      glycol) i.e. PEGylated lipids. Egg phosphatidylcholine vesicles with 5 mol% PEG
      were prepared with sizes ranging from 100 nm to 1 microm. Leakage was quantified
      in terms of temporal fluorescence intensity changes observed during carefully
      controlled ultrasound ON/OFF time intervals. Custom-built transducers operating
      at frequencies of 1.6 MHz (focused) and 1.0 MHz (unfocused) were used, the
      I(spta) of which were 46.9 W/cm2 and 3.0 W/cm2, respectively. A commercial 20
      kHz, point-source, continuous wave transducer with an I(spta) of 0.13 W/cm2 was
      also used for comparative purposes. Whereas complete leakage was obtained for all
      vesicle sizes at 20 kHz, no leakage was observed for vesicles smaller than 100 nm
      in diameter at 1.6 or 1.0 MHz. However, introducing leakage at the higher
      frequencies became feasible when larger (greater than 300 nm) vesicles were used,
      and the extent of leakage correlated well with vesicle sizes between 100 nm and 1
      microm. This observation suggests that physico-chemical membrane properties play
      a crucial role in ultrasound mediated membrane permeation and that low frequency
      (tens of kilohertz) ultrasound exposure is more effective in introducing
      permeability change than the "conventional" (1 MHz) therapeutic one. The
      experimental data also indicate that the leakage level is controlled by the
      exposure time. The results of this work might be helpful to optimize acoustic
      field and membrane parameters for gene or drug delivery. The outcome of this work
      might also be useful in wound management.

PMID- 16979208
TI  - Coronavirus nucleocapsid protein is an RNA chaperone.
AB  - RNA chaperones are nonspecific nucleic acid binding proteins with long disordered
      regions that help RNA molecules to adopt its functional conformation. Coronavirus
      nucleoproteins (N) are nonspecific RNA-binding proteins with long disordered
      regions. Therefore, we investigated whether transmissible gastroenteritis
      coronavirus (TGEV) N protein was an RNA chaperone. Purified N protein enhanced
      hammerhead ribozyme self-cleavage and nucleic acids annealing, which are
      properties that define RNA chaperones. In contrast, another RNA-binding protein,
      PTB, did not show these activities. N protein chaperone activity was blocked by
      specific monoclonal antibodies. Therefore, it was concluded that TGEV N protein
      is an RNA chaperone. In addition, we have shown that purified severe acute
      respiratory syndrome (SARS)-CoV N protein also has RNA chaperone activity. In
      silico predictions of disordered domains showed a similar pattern for all
      coronavirus N proteins evaluated. Altogether, these data led us to suggest that
      all coronavirus N proteins might be RNA chaperones.

PMID- 16979209
TI  - Kaposi's sarcoma herpesvirus C-terminal LANA concentrates at pericentromeric and
      peri-telomeric regions of a subset of mitotic chromosomes.
AB  - The Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear
      antigen (LANA) tethers KSHV terminal repeat (TR) DNA to mitotic chromosomes to
      efficiently segregate episomes to progeny nuclei. LANA contains N- and C-terminal
      chromosome binding regions. We now show that C-terminal LANA preferentially
      concentrates to paired dots at pericentromeric and peri-telomeric regions of a
      subset of mitotic chromosomes through residues 996-1139. Deletions within C
      terminal LANA abolished both self-association and chromosome binding, consistent
      with a requirement for self-association to bind chromosomes. A deletion
      abolishing TR DNA binding did not affect chromosome targeting, indicating LANA's
      localization is not due to binding its recognition sequence in chromosomal DNA.
      LANA distributed similarly on human and non-human mitotic chromosomes. These
      results are consistent with C-terminal LANA interacting with a cell factor that
      concentrates at pericentromeric and peri-telomeric regions of mitotic
      chromosomes.

PMID- 16979207
TI  - CD4 and MHC-I downregulation are conserved in primary HIV-1 Nef alleles from
      brain and lymphoid tissues, but Pak2 activation is highly variable.
AB  - HIV-1 compartmentalization in the CNS has been demonstrated for gag, pol, and env
      genes. However, little is known about tissue compartmentalization of nef genes
      and their functional characteristics in brain. We have cloned 97 nef genes and
      characterized 10 Nef proteins from autopsy brain and lymphoid tissues from 2
      patients with AIDS and HIV-1-associated dementia. Distinct compartmentalization
      of brain versus lymphoid nef genes was demonstrated within each patient. CD4 and
      MHC-I downregulation were conserved in all tissue-derived Nefs. However, MHC-I
      downregulation by brain-derived Nefs was weaker than downregulation by lymphoid
      derived Nefs. The motifs KEEE- or EKEE- at the PACS-1 binding site represented
      brain-specific signature patterns in these 2 patients and contributed to the
      reduced MHC-I downregulation activity of brain-derived Nefs from these patients.
      Pak2 association was highly variable in Nefs from both patients. Three of 10
      tissue-derived Nefs coimmunoprecipitated activated Pak2, with strong association
      demonstrated for only 2 Nefs. The ability of Nef to associate with activated Pak2
      did not correlate with brain or lymphoid tissue origin. Nef genes from viruses
      isolated from brain by coculture with PBMC were not closely related to sequences
      amplified directly from brain tissue, suggesting that viral selection or
      adaptation occurred during coculture. This study of tissue-derived HIV-1 Nefs
      demonstrates that CD4 and MHC-I downregulation are highly conserved Nef
      functions, while Pak2 association is variable in late stage AIDS patients.

PMID- 16979210
TI  - The porcine lymphotropic herpesvirus 1 encodes functional regulators of gene
      expression.
AB  - The porcine lymphotropic herpesviruses (PLHV) are discussed as possible risk
      factors in xenotransplantation because of the high prevalence of PLHV-1, PLHV-2
      and PLHV-3 in pig populations world-wide and the fact that PLHV-1 has been found
      to be associated with porcine post-transplant lymphoproliferative disease. To
      provide structural and functional knowledge on the PLHV immediate-early (IE)
      transactivator genes, the central regions of the PLHV genomes were characterized
      by genome walking, sequence and splicing analysis. Three spliced genes were
      identified (ORF50, ORFA6/BZLF1(h), ORF57) encoding putative IE transactivators,
      homologous to (i) ORF50 and BRLF1/Rta, (ii) K8/K-bZIP and BZLF1/Zta and (iii)
      ORF57 and BMLF1 of HHV-8 and EBV, respectively. Expressed as myc-tag or HA-tag
      fusion proteins, they were located to the cellular nucleus. In reporter gene
      assays, several PLHV-promoters were mainly activated by PLHV-1 ORF50, to a lower
      level by PLHV-1 ORFA6/BZLF1(h) and not by PLHV-1 ORF57. However, the ORF57
      encoded protein acted synergistically on ORF50-mediated activation.

PMID- 16979211
TI  - Multi-scale Cryptosporidium/sand interactions in water treatment.
AB  - Owing to its widespread occurrence in drinking water supplies and its significant
      resistance to environmental stresses, Cryptosporidium parvum is regarded as one
      of the most important waterborne microbial parasites. Accordingly, a substantial
      research effort has been aimed at elucidating the physical, chemical and
      biological factors controlling the transport and removal of Cryptosporidium
      oocysts in natural subsurface environments and drinking water treatment
      facilities. In this review, a multi-scale approach is taken to discuss the
      current state-of-knowledge on Cryptosporidium-sand interactions at a nano-scale,
      bench-scale and field-scale relevant to water treatment operations. Studies
      conducted at the nano-scale and bench-scale illustrate how techniques based on
      the principles of colloid and surface chemistry are providing new insights about
      oocyst-sand interactions during transport of Cryptosporidium oocysts in granular
      porous media. Specifically, atomic force microscopy and impinging jet experiments
      reveal the importance of oocyst surface biomolecules in controlling
      Cryptosporidium/sand interactions by a mechanism of steric hindrance. Traditional
      bench-scale column transport studies conducted over a broad range of experimental
      conditions highlight the role of physicochemical filtration and physical
      straining in the removal of oocysts from the pore fluid. Such experiments have
      also been used to evaluate the influence of biofilms formed on grain surfaces and
      the presence of natural organic matter on oocyst-sand interactions. Whilst
      filtration studies conducted at the plant-scale have been useful for evaluating
      the effectiveness of various materials as surrogates for Cryptosporidium oocysts,
      at this macro-scale, little could be learnt about the fundamental mechanisms
      controlling oocyst-sand interactions. This review of the literature on
      Cryptosporidium-sand interactions at different length scales points to the
      importance of combining studies at the plant-scale with well-controlled
      investigations conducted at the nano- and bench-scales. Furthermore, because
      oocyst surface properties play an important role in controlling the extent of
      interaction with sand surfaces, a thorough discussion of Cryptosporidium oocyst
      characteristics and electrical properties is presented.

PMID- 16979212
TI  - The methane sink associated to soils of natural and agricultural ecosystems in
      Italy.
AB  - In the present work, the CH4 sink associated to Italian soils was calculated by
      using a process-based model controlled by gas diffusivity and microbial activity,
      which was run by using a raster-based geographical information system.
      Georeferenced data included land cover CLC2000, soil properties from the European
      Soil Database, climatic data from the MARS-STAT database, plus several derived
      soils properties based on published algorithms applied to the above mentioned
      databases. Overall CH4 consumption from natural and agricultural sources
      accounted for a total of 43.3 Gg CH4 yr(-1), with 28.1 Gg CH4 yr(-1) removed in
      natural ecosystems and 15.1 Gg CH4 yr(-1) in agricultural ecosystems. The highest
      CH4 uptake rates were obtained for natural areas of Southern Apennines and
      islands of Sardinia and Sicily, and were mainly associated to areas covered by
      sclerophyllous vegetation (259.7+/-30.2 mg CH4 m(-2) yr(-1)) and broad-leaved
      forest (237.5 mg CH4 m(-2) yr(-1)). In terms of total sink strength broad-leaved
      forests were the dominant ecosystem. The overall contribution of each ecosystem
      type to the whole CH4 sink depended on the total area covered by the specific
      ecosystem and on its exact geographic distribution. The latter determines the
      type of climate present in the area and the dominant soil type, both factors
      which showed to have a strong influence on CH4 uptake rates. The aggregated CH4
      sink, calculated for natural ecosystems present in the Italian region, is
      significantly higher than previously reported estimates, which were extrapolated
      from fluxes measured in other temperate ecosystems.

PMID- 16979213
TI  - Fluorescence of sediment humic substance and its effect on the sorption of
      selected endocrine disruptors.
AB  - Humic substances (HS) have a critical influence on the sorption of organic
      contaminants by soils and sediments. This paper describes investigations into the
      sorption behavior of three representative endocrine disruptors, bisphenol A
      (BPA), 17beta-estradiol (E2), and 17alpha-ethynylestradiol (EE2), onto sediments
      and HS extracted sediments using a batch technique. The organic carbon-normalized
      partition coefficients (K(oc)) for the extracted HS (K(oc)(hs)) were calculated,
      and the fluorescence spectra of the HS extraced from different sediment samples
      were gained using excitation/emission matrix (EEM). Particular attention was paid
      to the correlations between the fluorescence characteristics of HS and the log
      K(oc)(hs) of selected endocrine disruptors. The results show that the log
      K(oc)(hs) values range from 3.14 to 4.09 for BPA, from 3.47 to 4.33 for E2, and
      from 3.65 to 4.32 for EE2. Two characteristic excitation-emission peaks were
      observed for HS samples extracted from sediments. They are located at Ex/Em=250
      260 nm/400-450 nm (peak alpha') and Ex/Em=310-330 nm/390-400 nm (peak alpha)
      respectively. The alpha' and alpha peak relative intensities I(alpha')/I(alpha)
      vary from 0.46 to 1.64 for different extracted HS samples. The similarity between
      fulvic acids (FA) Ex/Em pairs and those observed for HS indicates that FA is the
      predominant fraction of HS extracted from sediments. Moreover, the log K(oc)(hs)
      values of BPA, E2, and EE2 have a negative linear correlation to
      I(alpha')/I(alpha) values. Peak alpha is often attributed to relatively stable
      and high molecular weight aromatic fulvic-like matter. Therefore, the result
      presented here reveals that the abundance of aromatic rings in HS molecular
      structure plays a critical role in the sorption of selected endocrine disruptors.

PMID- 16979214
TI  - Clay charge reversal effects on aqueous polymer sorption on lateritic soils.
AB  - The effects of charge reversal about the measured point of zero charge (pH(0)
      approximately 5.2) of untreated and treated Sete Lagoas lateritic soil of Brazil
      on aqueous polymer sorption was investigated. The polymers are anionic sodium
      carboxymethyl cellulose (CMCA), nonionic polyethylene oxide (PEO), and cationic
      polyacrylamide (PAM). They were prepared at aqueous concentrations and pH ranges
      of 0.1-2.0 g l(-1) and 2-9, respectively. Soil treatment involved the removal of
      iron oxides by treatment with dithionate-bicarbonate-citrate. Batch sorption test
      results show that the presence of iron oxides in lateritic soil tends to suppress
      sorption of CMCA (especially at pH=pH(0)) and PEO (for the whole pH range) but
      has uncertain effects on cationic PAM sorption. CMCA sorption on the untreated
      soil improves on either side of pH(0), in direct proportionality to solution
      concentration, except at pH<4.0, where disassociation of the polymer molecules
      may decrease sorption energy. Increase in the sorption of non-cationic polymers
      (CMCA and PEO) at pH>pH(0) is attributable to dispersion of clay, cation bridging
      and polymer molecular reconfiguration. For cationic PAM, electrostatic bonding to
      negatively charged soil particle surfaces accounts for the sorption increase. For
      treated soil samples, polymer sorption pattern is similar to those expected for
      the montmorillonitic clayey soils of temperate zones. These results indicate that
      the pH(0) of lateritic soils, within the regime that exists in the field, should
      be considered in assessing the potential effectiveness of polymer dust
      suppressants for tropical lateritic soils.

PMID- 16979215
TI  - Precipitation of Zn(II), Cu(II) and Pb(II) at bench-scale using biogenic hydrogen
      sulfide from the utilization of volatile fatty acids.
AB  - Biological production of hydrogen sulfide (H(2)S) using sulfate-reducing bacteria
      (SRB) has important potential within environmental biotechnology. The aim of this
      work was to study the possibility of using SRB for the treatment of an acid mine
      drainage (AMD) at bench-scale. This process involved three stages: the
      optimization of H(2)S production through the utilization of total volatile fatty
      acids (TVFAs) by SRB, the establishment of a biofilm reactor for sulfide
      production, and the precipitation of metals by using the biologically produced
      H(2)S. The substrates used for TVFAs production consisted of papaya, apple and
      banana. The H(2)S produced from the degradation of TVFAs was utilized for the
      precipitation of a metal-contaminated effluent collected from Bolivar mine
      (Oruro, Bolivia). The maximum concentration of H(2)S obtained was approximately
      16mM. Removal efficiencies of ca. 100% for copper, above 94% for zinc, and above
      92% for lead were achieved.

PMID- 16979216
TI  - Optimal growth of Dunaliella primolecta in axenic conditions to assay herbicides.
AB  - To develop an assay for herbicides in marine environments using microalgae, we
      have optimized the specie, cell culture media and physical conditions to obtain
      maximal cellular densities in a 96 well micro format to allow mass assays. We
      first surveyed several species of 7 unicellular eukaryotic algae genera
      (Dunaliella, Tetraselmis, Chlorella, Ellipsoidon, Isochrysis, Nannochloropsis,
      and Phaeodactylum) for vigorous in vitro axenic growth. Once the genus Dunaliella
      was selected, Dunaliella primolecta was preferred among 9 species (bioculata,
      minuta, parva, peircei, polymorpha, primolecta, quartolecta, salina and
      tertiolecta) because it showed the highest growth rates. The components (oligo
      elements, sugars, amino acids and vitamins) and conditions (light, CO(2),
      temperature) of the culture media were further optimized to obtain the highest
      cellular densities (up to 60x10(6)cellsml(-1)) and the shortest cell cycle
      duration ( approximately 12h) for D. primolecta. Then the toxicity of four
      representative herbicides, alloxydim, and sethoxydim (inhibitors of acetyl-coA
      carboxilase), metamitron (inhibitor of photosynthesis) and clopyralid (inhibitor
      of respiration), were assayed on the optimal culture conditions for D. primolecta
      during 96h. The results showed that D. primolecta was susceptible to those
      herbicides in the following order: metamitron > sethoxydim > alloxydim. In
      contrast, clopyralid did not have any effects. Therefore, D. primolecta
      microcultures can be used to assay a large number of samples for the presence of
      herbicides under a saline environment.

PMID- 16979217
TI  - Irgarol inhibits the synthesis of ATP in mitochondria from rat liver.
AB  - The interactions of Irgarol with rat liver mithocondrial have been investigated.
      The results indicate that Irgarol inhibits the ATP synthesis. The analysis of the
      various steps involved in the ATP synthesis suggests that the inhibition is due
      to the opening of small-size pores.

PMID- 16979218
TI  - Biologically directed environmental monitoring, fate, and transport of estrogenic
      endocrine disrupting compounds in water: A review.
AB  - Endocrine disrupting compounds (EDCs) are contaminants that may be hormonally
      active at low concentrations and are emerging as a major concern for water
      quality. Estrogenic EDCs (e-EDCs) are a subclass of EDCs that, when organisms are
      exposed to them, function as estrogens. Given that there are numerous e-EDCs that
      can negatively affect humans and wildlife, general screening techniques like
      biologically based assays (BBAs) may provide major advantages by estimating the
      total estrogenic effects of many e-EDCs in the environment. These techniques may
      potentially be adapted for field portable biologically directed sampling and
      analyses. This article summarizes available BBAs used to measure estrogenic e
      EDCs in the environmental samples and also presents results relating to fate and
      transport of e-EDCs. Estrogenic EDCs appear to be almost ubiquitous in the
      environment, despite low solubility and high affinity of organic matter.
      Potential transport mechanisms may include: (1) transport of more soluble
      precursors, (2) colloid facilitated transport, (3) enhanced solubility through
      elevated pH, and (4) the formation of micelles by longer-chain ethoxylates. Due
      to their persistent and ubiquitous nature, source control strategies for e-EDCs
      may reduce influent concentration to wastewater treatment plants so that the post
      treatment effluent will decrease concentrations to estrogenically inactive
      levels. Alternatively if source reduction is not possible, then more testing is
      needed on tertiary treatment technologies and treatment efficiencies for e-EDCs.
      There is still a need for research on remediation and restoration approaches for
      habitats disturbed by elevated e-EDC concentrations.

PMID- 16979219
TI  - Comparative study of immobilized Trametes versicolor laccase on nanoparticles and
      kaolinite.
AB  - Laccase from Trametes versicolor was immobilized on nanoparticles and kaolinite
      by physical adsorption or chemical covalence in which the supporters were
      activated by cross-linked with glutaraldehyde. Thermal and pH stabilities of
      immobilized laccase on these different supporters were compared. The degradation
      efficiencies of these immobilized laccases on oxidation of benzo[a]pyrene (BaP)
      were also compared. The results showed that the immobilized laccases on
      nanoparticles were more stable in resisting pH and thermal changes. After 48h
      oxidation, laccase immobilized on kaolinite using the covalent coupling method
      showed a higher efficiency of oxidation with the BaP residue of 23% in the
      presence of 1mM HBT and with BaP residue of 37% in 1mM ABTS as the mediator. The
      results also exhibited a significant inhibition by 1% surfactant Tween 80.
      According to the HPLC analysis, the oxidation products including 1,6
      benzo[a]pyrene quinone, 3,6-benzo[a]pyrene quinone and 6,12-benzo[a]pyrene
      quinone were identified.

PMID- 16979220
TI  - New Neandertal remains from Cova Negra (Valencia, Spain).
AB  - New Neandertal fossils from the Mousterian site of Cova Negra in the Valencia
      region of Spain are described, and a comprehensive study of the entire human
      fossil sample is provided. The new specimens significantly augment the sample of
      human remains from this site and make Cova Negra one of the richest human
      paleontological sites on the Iberian Peninsula. The new specimens include cranial
      and postcranial elements from immature individuals and provide an opportunity to
      study the ontogenetic appearance of adult Neandertal characteristics in this
      Pleistocene population. Children younger than 10 years of age constitute four of
      the seven minimum number of individuals in the sample, and this relative
      abundance of children at Cova Negra is similar that in to other Neandertal sites
      in Europe and southwest Asia. The recognition of diagnostic Neandertal features
      in several of the specimens, as well as their western European context and late
      Pleistocene age, suggests that all the human remains from Cova Negra represent
      Neandertals. The archaeological evidence from Cova Negra indicates sporadic,
      short-term occupations of the site, suggesting a high degree of mobility among
      Neandertals.

PMID- 16979221
TI  - Correlated resistance to glucose deprivation and cytotoxic agents in fibroblast
      cell lines from long-lived pituitary dwarf mice.
AB  - Fibroblast cell lines derived from the skin of young adult mice of the long-lived
      Snell dwarf mutant mouse stock have been shown to be resistant to the cytotoxic
      effects of multiple agents, including hydrogen peroxide, cadmium, heat,
      ultraviolet light, and the carcinogen methyl methanesulfonate. Snell dwarf
      fibroblasts are here reported to differ from control cell lines in two other
      respects: they are relatively resistant to the metabolic inhibition induced by
      low glucose concentrations, and also resistant to the effects of the
      mitochondrial poison rotenone, a blocker of Complex I of the electron transport
      chain. Furthermore, analysis of cell lines derived from a group of genetically
      heterogeneous mice established that cell lines resistant to peroxide-induced
      cytotoxicity were also relatively resistant to death induced by paraquat,
      cadmium, and ultraviolet light. Resistance to the metabolic effects of low
      glucose medium was associated with resistance to peroxide and cadmium in cells
      from heterogeneous mice and Snell dwarf mice, though unexpectedly not associated
      with resistance to the lethal effects of paraquat or UV light. Further analysis
      of the basis for metabolic abnormalities in these cell lines may provide insights
      into the cause of stress resistance in dwarf-derived cultures and to the
      longevity and disease-resistance of these long-lived mutant mice.

PMID- 16979222
TI  - Estimation of daily traffic emissions in a South-European urban agglomeration
      during a workday. Evaluation of several "what if" scenarios.
AB  - Detailed traffic data collected from seven major roads in the city of Athens,
      Greece are presented and analysed in this study. Vehicles are split into seven
      categories while vehicle speed is also recorded. Based on these data the
      emissions of five major pollutants (CO, Benzene, NO(X), PM(10) and VOCs) were
      calculated with the aid of the COPERT methodology and, based on these results, an
      Artificial Neural Network was also developed. The results of the two
      methodologies were compared and it was found that the differences were very
      small. The ANN model seems to be a reliable alternative to calculate road traffic
      emissions in a busy road environment. The results reflect the spatial and
      temporal distribution of the concentrations of the pollutants examined.
      Alternative "what if" scenarios of the fleet distribution were also applied by
      means of environmental policy. Since Athens experiences low air quality
      conditions the correct estimation of traffic emissions is crucial since they play
      a significant role in the design of an environmental abatement strategy.

PMID- 16979223
TI  - Heavy incense burning in temples promotes exposure risk from airborne PMs and
      carcinogenic PAHs.
AB  - We present the mechanistic-based exposure and risk models, appraised with
      reported empirical data, to assess how the human exposure to airborne particulate
      matters (PMs) and carcinogenic polycyclic aromatic hydrocarbons (PAHs) during
      heavy incense burning episodes in temples. The models integrate size-dependent PM
      levels inside a temple from a published exploratory study associated with a human
      expiratory tract (HRT) model taking into account the personal exposure levels and
      size distributions in the HRT. The probabilistic exposure profiles of total-PAH
      levels inside a temple and internal PAHs doses are characterized by a
      physiologically based pharmacokinetic (PBPK) model with the reconstructed dose
      response relationships based on an empirical three-parameter Hill equation model,
      describing PAHs toxicity for DNA adducts formation and lung tumor incidence
      responses in human white blood cells and lung. Results show that the alveolar
      interstitial (AI) region has a lower mass median diameter (0.29 microm) than that
      in extrathoracic (ET(1), 0.37 microm), brochial (BB, 0.36 microm) and bronchiolar
      (bb, 0.32 microm) regions. The 50% probability (risk=0.5) of exceeding the DNA
      adducts frequency (DA(f)) ratio of 1.28 (95% CI: 0.55-2.40) and 1.78 (95% CI:
      0.84-2.95) for external exposure of B[a]P and B[a]P(eq), respectively. The 10%
      (risk=0.1) probability or more of human affected by lung tumor is approximately
      7.62x10(-5)% (95% CI: 3.39x10(-5)-1.71x10(-4)%) and 3.87x10(-4)% (95% CI:
      1.72x10(-4)-8.69x10(-4)%) for internal exposure of B[a]P and B[a]P(eq),
      respectively. Our results implicate that exposure to smoke emitted from heavy
      incense burning may promote lung cancer risk. Our study provides a quantitative
      basis for objective risk prediction of heavy incense burning exposure in temples
      and for evaluating the effectiveness of management.

PMID- 16979224
TI  - A novel modelling approach for evaluating the preindustrial natural carrying
      capacity of human population in Iceland.
AB  - The pre-industrial natural carrying capacity is believed to have limited the
      human population in Iceland to a maximum of fifty to sixty thousand inhabitants.
      Since AD 1800 the Icelandic population has gradually grown up to nearly 300
      thousand in 2005. In this paper a simple approach is used to evaluate the
      potential population size that the pre-industrial Icelandic environment could
      possibly sustain. A dynamic model was constructed that simulates the population
      size according to potential biological production available for livestock.
      Biological production was determined by the extent of the total potential
      vegetation cover based on the Degree-Day concept. Fluctuations in the mean annual
      temperature causes changes in the potential vegetation cover and as a consequence
      change the biological production sustaining livestock and ultimately human
      population. The simulation's results indicate that the potential population that
      the Icelandic environments could sustain during the pre-industrial period
      fluctuated between 40 and 80 thousand. The results further indicate that the
      severe land degradation experienced after the Viking settlement period in AD 900
      had a marginal impact on the population size. The pre-historical population did
      however overshoot the natural sustainability on several occasions.

PMID- 16979225
TI  - Pro-thrombotic and pro-oxidant effects of diet-induced hyperhomocysteinemia.
AB  - Elevated plasma homocysteine levels are associated with the risk of
      atherosclerosis and arterial and venous thrombosis. We have previously
      demonstrated that rabbits rendered hyperhomocysteinemic by parenteral
      administration of homocysteine develop a dysfibrinogenemia that is associated
      with the formation of fibrin clots that are abnormally resistant to fibrinolysis.
      We suggested that this acquired dysfibrinogenemia contributes to the thrombotic
      tendency in hyperhomocysteinemia. However, it was possible that the homocysteine
      associated dysfibrinogenemia was an artifact of the parenteral administration
      model. Therefore, the goals of the current study were to develop a diet-induced
      model of homocysteinemia in rabbits and determine whether a dysfibrinogenemia and
      evidence of oxidative stress develop in this model as they do when homocysteine
      is injected. We found that rabbits fed a diet severely deficient in folate and
      mildly deficient in choline develop mild hyperhomocysteinemia: 14.8+/-4.0 microM
      in deficient rabbits compared to 9.0+/-1.7 microM in controls. The deficient
      rabbits also develop evidence of oxidant stress: increased lipid peroxidation in
      liver, impaired mitochondrial enzyme activities in liver and elevated caspase-3
      levels in plasma. Most importantly, the deficient rabbits also develop a
      dysfibrinogenemia characterized by increased resistance to fibrinolysis. We
      believe that this dietary model of homocysteinemia is clinically relevant and
      reproduces many features associated with hyperhomocysteinemia in previous work
      using in vitro and in vivo models. Our findings suggest that an acquired
      dysfibrinogenemia could play a role in the increased risk of atherothrombotic
      disease in mildly hyperhomocysteinemic human subjects.

PMID- 16979226
TI  - Antinociceptive tolerance revealed by cumulative intracranial microinjections of
      morphine into the periaqueductal gray in the rat.
AB  - The periaqueductal gray (PAG) appears to play a key role in morphine
      antinociception and tolerance. The objective of this manuscript is to develop a
      cumulative dose microinjection procedure so the hypothesized role of the PAG in
      morphine antinociceptive tolerance can be assessed using dose-response analysis.
      Rats were implanted with a guide cannula into the ventrolateral PAG.
      Microinjection of cumulative half log doses of morphine (0.32, 1, 3.2, and 10
      micro g/0.4 micro l) produced antinociception on the hot plate test only at the
      two highest doses. Microinjection of quarter log doses of morphine into the PAG
      (1, 1.8, 3.2, 5.6, and 10 micro g/0.4 micro l) resulted in an ED(50) for
      antinociception of 1.8 mug. Systemic administration of the opioid antagonist
      naloxone increased the morphine ED(50) to 9.0 micro g. Repeated microinjections
      of saline into the PAG had no effect on nociception. Pretreatment with twice
      daily injections of morphine, either systemically (5 mg/kg, s.c.) or into the PAG
      (5 micro g/0.4 micro l), for 2 days produced a two-fold increase in the ED(50)
      for morphine antinociception. These data validate the use of an intracranial
      cumulative dose procedure to assess morphine potency and demonstrate that
      microinjection of morphine into the PAG is sufficient to produce tolerance.

PMID- 16979227
TI  - Gabapentin enhances the analgesic response to morphine in acute model of pain in
      male rats.
AB  - Whenever opioids as drug of choice result in inadequate analgesia, the
      combinational therapy would be the solution. In this study the co-administration
      of gabapentin with morphine is evaluated in acute model of pain. Therefore the
      antinociceptive effect of gabapentin (30 or 90 mg/kg, s.c.) and morphine (0.5, 1
      or 3 mg/kg, s.c.) alone or in combination were measured by tail-flick test in
      intact adult male rats. Control rats received normal saline. Tail-flick latency
      time and Area Under Curve (AUC), as antinociception index were calculated for
      each groups. There was not any significant difference between the antinociceptive
      response of 0.5 mg/kg morphine and 30 mg/kg gabapentin as compared to controls,
      but co-administration of these subanalgesic doses increased significantly AUC as
      compared to morphine alone. The co-administration of gabapentin with analgesic
      doses of 1 and 3 mg/kg morphine had also increased significantly AUC. Therefore
      gabapentin enhanced the antinociceptive effect of both analgesic and subanalgesic
      doses of morphine in a dose dependent manner. In conclusion co-administration of
      gabapentin with low doses of morphine produced therapeutic analgesia which could
      have important clinical application.

PMID- 16979228
TI  - Improved in vitro bovine embryo development and increased efficiency in producing
      viable calves using defined media.
AB  - In this study, we developed a defined culture medium that supported improved in
      vitro bovine embryo development and calving rate after embryo transfer (ET). In
      vitro-matured bovine oocytes from abbatoir-derived ovaries from Korean native,
      HanWoo cattle were fertilized with frozen-thawed spermatozoa and embryos were
      cultured in two-step culture media. In Experiment 1, embryos were cultured in
      media supplemented with 8 mg/mL BSA, or 0.1mg/mL PVA and 8 mg/mL BSA+2.77 mM myo
      inositol or 0.1mg/mL PVA+2.77 mM myo-inositol. Although defined culture media
      containing PVA supported lower developmental competence compared to undefined
      media (containing BSA; 8% versus 34%, respectively), defined culture media
      containing 2.77 mM myo-inositol increased rates of blastocyst formation up to
      28%. In Experiment 2, the effect of energy substrate (1.5mM glucose or 1.2mM
      phosphate) in PVA-myo-inositol defined culture medium on in vitro embryo
      development was investigated. Defined culture media containing PVA, myo-inositol
      and phosphate supported better embryo development to blastocysts compared to
      medium supplemented with both glucose and phosphate (43% versus 31%). In
      Experiment 3, the effect of epidermal growth factor (EGF) in PVA+myo-inositol
      phosphate two-step culture medium on in vitro embryo development was
      investigated. Among 0, 1, 10 and 100 ng/mL EGF concentrations, the maximal effect
      was observed with 10 ng/mL EGF (52% blastocyst formation). In Experiment 4, total
      cell number and calving rate were compared between defined PVA-myo-inositol
      phosphate-EGF medium and undefined medium containing BSA, glucose and phosphate.
      No differences in total cell number of blastocysts obtained from the two groups
      were observed, however, the rate of viable offspring production was increased
      using the defined culture medium, compared to the undefined culture medium. In
      Experiment 5, the relative abundance of mRNA transcripts [interferon-tau (If
      tau), glucose transporter-1 (glut-1) and insulin like growth factor 2 receptor
      (Igf2r)] were analyzed in blastocysts derived from undefined or defined culture
      media. Gene expression of If-tau, glut-1 was significantly increased in defined
      culture medium compared to undefined medium. In conclusion, chemically defined
      culture media without BSA or FBS improved developmental competence of in vitro
      cultured bovine embryos and delivery of viable calves after ET.

PMID- 16979229
TI  - Logistic regression analysis of pregnancy rate following transfer of Bos indicus
      embryos into Bos indicus x Bos taurus heifers.
AB  - Factors affecting pregnancy rate of 5627 Zebu embryos in crossbred females with
      unknown proportions of Holstein and Zebu breeding were examined. After evaluation
      for developmental stage, quality, and viability, embryos were immediately
      transferred to recipients. Pregnancy diagnosis was conducted approximately 53 d
      after transfer; pregnancy rate was coded as a binomial event and analyzed using
      logistic regression models. Maximum likelihood methodology and the likelihood
      ratio statistic were used to estimate regression coefficients and test
      hypotheses. Explanatory variables were year of transfer (1992-1999), season of
      transfer (summer, autumn, winter and spring), breed of the embryo (Guzerat, Gyr
      or Nellore), stage of the embryo (morula, early blastocyst, blastocyst, expanded
      blastocyst, and hatching blastocyst), quality of the embryo (excellent, good or
      regular), and donor-recipient synchrony (estrus in the recipient occurred 2-3 d
      before, 1 d before, the day of, 1 d after, or 2-3 d after estrus in the donor).
      Average pregnancy rate was 63.7%. Pregnancy rates were not significantly affected
      by breed of embryo. The best multiple-logistic model to explain the pregnancy
      result included the effects of year and season of transfer, embryo stage and
      quality, and estrous synchrony between donor and recipient (P<or=.01). High
      pregnancy rates occurred when transfers occurred in autumn, early blastocysts or
      morulae were transferred, and excellent quality embryos were chosen. In addition,
      pregnancy rates were highest when estrus in the recipient began 1 d earlier than
      that of the donor.

PMID- 16979230
TI  - Effect of loading method on the fracture mechanics of two layered all-ceramic
      restorative systems.
AB  - OBJECTIVE: The aim of this research was to evaluate both the fracture and impact
      strength of two core veneered all-ceramic systems and to reveal whether the speed
      of loading affects fracture mechanism. METHODS: The absorbed energy by
      (IPS)Empress-Eris crowns and Cercon-Ceram S crowns in a fracture strength test
      was compared by the energy absorbed in an impact strength test. The principles of
      fractography were used to identify fracture origin and dimensions and to
      calculate the stress at failure. Finite element analysis (FEA) was used to
      rationalize the results. RESULTS: For the (IPS)Empress 2-Eris crowns, there was a
      significant difference in the energy absorbed for the fracture test and the
      impact test, where for the Cercon-Ceram S, there was no significant difference.
      Despite the high strength of the zirconia cores there was no significant
      difference in the energy absorbed between the two systems in the impact strength
      test. The dominant mode of failure of layered all-ceramic restorations under
      occlusal loading is cone cracking in the veneering ceramic. SIGNIFICANCE: It was
      concluded that to exploit the high strength of the zirconia cores the strength of
      the veneering ceramic has to improve as delamination and cone cracking of the
      veneer are the most expected failure modes.

PMID- 16979231
TI  - Surflan and oryzalin impair reproduction in the teleost medaka (Oryzias latipes).
AB  - We conducted studies to determine if the xenoestrogens Surflan and its active
      ingredient oryzalin, affect indices of reproductive fitness in medaka (Oryzias
      latipes). Oryzalin (0.5, 0.25mg/l) or Surflan (2.0 microl/l) and oryzalin
      (0.5mg/l) significantly increased the mean number of non-fertilized eggs produced
      by treated females paired with untreated males, or by untreated females paired
      with treated males. Oryzalin (1.0, 0.5, 0.25mg/l) and Surflan (3.8, 2.0, 1.0
      microl/l) significantly affected the time to hatch of eggs from treated females
      paired with untreated males, and from untreated females paired with treated
      males. Surflan (3.8, 2.0, 1.0 microl/l) induced intersex lesions in 80-100% of
      males. Oryzalin-exposed males exhibited a significant increase in the incidence
      of necrotic spermatids and necrotic spermatogonia, while oryzalin-exposed females
      had significantly fewer immature oocytes and an increase in the occurrence of
      hyperplastic ovaries. Our results indicate that Surflan and oryzalin affect both
      reproduction and gonadal histology in male and female medaka.

PMID- 16979232
TI  - Physico-chemical analysis of G-quadruplex containing bunch-oligonucleotides.
AB  - A growing number of evidences suggest that DNA G-quadruplex structures play an
      important role in many relevant biological processes. The introduction of
      chemical modifications in quadruplex structures could enhance the in vivo
      biological activity. The correlation between the physico-chemical properties and
      chemical modifications represents an essential step toward the de novo design of
      quadruplex forming oligonucleotides for biomedical applications. We report the
      physico-chemical characterisation of a quadruplex formed by a bunch of four
      d(TG4T) oligonucleotides whose 3'-ends are linked together by a tetra-branched
      linker. The study was performed by circular dichroism, gel electrophoresis and
      molecular modelling techniques. The data indicate an high stability for this kind
      of quadruplex and add some information on the role of the tetra-branched linker
      on the quadruplex stability.

PMID- 16979233
TI  - Effect of temperature on alpha olefin sulfonate induced softening of gelatin
      hydrogels.
AB  - Dynamic light scattering (DLS) and oscillatory rheology experiments were
      performed to study temperature dependence (T=10-25 degrees C) of the interactions
      in hydrogels of gelatin with AOS (alpha olefin sulfonate, anionic surfactant) for
      surfactant concentrations in the range 25-100 mM, chosen larger than cmc
      (approximately 8mM). The network mesh size (xi) values deduced from fastmode
      diffusivity (D(f)) data obtained from dynamic structure factor measurements, S(q,
      t) approximately exp(-D(f)q(2)t) (for t<or=1 ms and q being the scattering wave
      vector), of micelle-bound gelatin gels was analyzed within the framework of Flory
      Rhener theory of cross-linking, which revealed a temperature dependence, xi
      approximately (0.5-chi)(1/5)exp(-DeltaG(Total)/RT) where chi is the Flory-Huggins
      interaction parameter, the free-energy of the gel-surfactant complex is
      DeltaG(Total) and R is universal gas constant. The low-frequency isochronal
      storage, G' and loss, G'' modulii revealed a transition from the rigid to a
      softened gel state occurring at surfactant concentration close to 55 mM,
      independent of temperature. The free-energy of interaction between gel and
      surfactant deduced from Arrhenius plots obtained from temperature dependent
      rheology, and light scattering data support this observation.

PMID- 16979234
TI  - Macrophage matrix metalloproteinase-2/-9 gene and protein expression following
      adhesion to ECM-derived multifunctional matrices via integrin complexation.
AB  - Macrophages are commonly observed at the biomaterial-tissue interface and
      interact with the extracellular matrix (ECM) mainly by integrin receptors to play
      a critical role in ECM turnover by secreting matrix metalloproteinases (MMPs). To
      investigate beta1 and beta3 containing integrin-mediated adhesion and subsequent
      MMP-2/-9 protein and gene expression in human blood-derived monocytes,
      biofunctional peptides immobilized onto flexible polyethylene glycol (PEG) arms
      were grafted onto a gelatin-based interpenetrating network (IPN). Adherent
      monocyte density was dramatically greater in the presence of RGD immobilized onto
      flexible PEG arms of the gelatin-based IPN. Pretreatment of monocytes with either
      anti-integrin beta1 or beta3 led to a significant decrease in adherent cell
      density on RGD-PEG-grafted IPNs. MMP-2 and MMP-9 protein and MMP-9 mRNA
      expression increased in the presence of IPNs initially, independent of ligand
      identity. Anti-integrin beta1 or beta3 antibody pretreatment of monocytes led to
      a general decrease in MMP-2/-9 protein expression. These results demonstrate the
      importance of beta1 and beta3 containing integrins in mediating monocyte adhesion
      onto RGD immobilized onto flexible PEG arms of the IPN. The results also reveal
      that MMP-2/-9 protein and gene expression is influenced by the presence of
      gelatin and not the ligands immobilized on the PEG arms of the IPN.

PMID- 16979235
TI  - Isodicentric Philadelphia chromosome in acute lymphoblastic leukemia with
      der(7;12)(q10;q10).
AB  - We describe here the first case of acute lymphoblastic leukemia (ALL) with an
      isodicentric Philadelphia [idic(Ph)] chromosome. A 35-year-old man was diagnosed
      as ALL because of the infiltration of CD10(+)CD19(+)CD33(+)CD34(+) lymphoblasts
      in the bone marrow and the expression of p190-type BCR/ABL fusion transcript.
      Chromosome analysis showed 45,XY,der(7;12)(q10;q10),der(9)t(9;22)(q34;q11),idic
      der(22)t(9;22)(q34;q11). The idic(Ph) chromosome was spindle-shaped and supposed
      to be formed by two Ph chromosomes joined at their q terminals, whereas idic(Ph)
      chromosomes in chronic myelogenous leukemia (CML) have been shown to be fused at
      the satellite regions of p arms. The results indicate that the structure of
      idic(Ph) chromosomes appears to be different between ALL and CML. The patient did
      not respond to any chemotherapy and could not achieve remission. This chromosome
      aberration in ALL may suggest poor prognosis as observed in some cases of CML.
      Furthermore, considering other three reported cases, der(7;12)(q10;q10) may be
      one of the recurrent translocations in ALL.

PMID- 16979236
TI  - Contrasting features of MDR phenotype in leukemias by using two fluorochromes:
      implications for clinical practice.
AB  - The expression and activity of P-glycoprotein (Pgp) and multidrug resistance
      associated protein (MRP1) were analyzed in 178 leukemia samples. Rhodamine-123
      (Rho-123) and DiOC(2) were used as substrate to evaluate efflux pump activity.
      Chronic myeloid leukemia (CML) exhibited a higher percentage of positivity using
      Rho-123 than DiOC(2) (p=0.000) as compared to other types of leukemia. Moreover,
      Rho-123 was able to detected Pgp positive cells in a higher proportion of samples
      than DiOC(2) samples (p=0.004). Similarly, MRP1 positive cells were best detected
      by Rho-123 as opposed to DiOC(2) (p=0.003). The co-functionality of Rho-123 and
      DiOC(2) was observed in 26 out of 105 (24.8%) leukemic samples. Co-expression
      between Pgp and MRP1 was detected in 30 out of 56 (53.6%) samples. As a whole,
      when the same samples were analyzed, Rho-123 was able to detect Pgp positive
      cells in a higher proportion of samples than DiOC(2) (p=0.000). Similarly, MRP1
      positive cells were best detected by Rho-123 as opposed to DiOC(2) (p=0.007). Our
      results support the idea that Rho-123 is the substrate of choice for leukemic
      cells.

PMID- 16979237
TI  - Moving from blame to quality: how to respond to failures in child protective
      services.

PMID- 16979239
TI  - Temporal coding in the gustatory system.
AB  - Early investigations of temporal coding in the gustatory system showed that the
      time course of responses in some neurons showed systematic differences across the
      various classes of taste stimuli, implying that the temporal characteristics of a
      response can convey information about a taste stimulus. Studies of temporal
      coding in the gustatory system have grappled with several unique methodological
      challenges, including the quantitative description and comparison of temporal
      patterns as well as the assessment of the relative contributions of spatial and
      temporal coding to the information contained in a response to a tastant. Other
      investigations have suggested that the cooperative activity among synchronously
      firing ensembles of taste-responsive neurons at all levels of processing in the
      brain can convey information about taste quality (sweet, sour, salty, bitter and
      umami). Behavioral studies using patterned electrical stimulation of the brain in
      awake animals have supported the idea that temporal coding of taste stimuli may
      have functional significance.

PMID- 16979238
TI  - Evaluation of a recombinant LipL41 antigen of Leptospira interrogans serovar
      canicola in ELISA for serodiagnosis of bovine leptospirosis.
AB  - The efficacy of a recombinant leptospiral lipoprotein LipL41 as an antigen for
      conducting enzyme-linked immunosorbent assay (ELISA) for diagnosis of bovine
      leptospirosis was evaluated. Using known positive and known negative cattle sera
      the recombinant antigen was found to be highly reactive in the concentration of
      100 ng/well. Using a total of 321 field cattle sera the sensitivity of ELISA as
      compared to microscopic agglutination test (MAT) was calculated to be 100%
      whereas the specificity was 85.3%. The seropositivity of leptospirosis among
      bovine population was found to be 21.18% having the predominance of serovars
      Sejroe and Pomona. It was concluded that rLipL41 protein could be a putative
      diagnostic candidate for serodiagnosis of bovine leptospirosis.

PMID- 16979240
TI  - Role of the C3b-binding site on C4b-binding protein in regulating classical
      pathway C5 convertase.
AB  - A high affinity C5 convertase is generated when a C3 convertase deposits
      additional C3b molecules on and around itself thereby switching the substrate
      specificity of C3 convertase from C3 to C5. In the present study the role of the
      additional C3b molecules in influencing the regulation of classical pathway C5
      convertase by C4b-binding protein (C4BP) was examined and compared to its
      precursor, the C3 convertase. Determination of IC(50) for inhibiting formation of
      the high affinity C5 convertase and for enhancing its decay (72 and 20 nM) were
      found to be similar to those obtained for the surface-bound C3 convertase (35 and
      11 nM). No difference was observed in the cofactor activity of C4BP for surface
      bound C4b alone or when in complex with C3b. Analysis of binding interactions
      between C4BP and EAC1,C4b cells revealed an average apparent dissociation
      constant (12 nM) similar to that obtained with EAC1,C4b cells with C3b on them
      (11 nM). Increasing the C4b or C3b density on the cell surface did not alter the
      affinity of C4BP. The data suggest that C4BP regulates the C5 convertase by
      mechanisms similar to those observed for the C3 convertase. Since the IC(50) for
      inhibiting formation of the soluble C3 convertase (5 nM) is 50-80-fold below the
      normal serum concentration of C4BP (250-400 nM), C4BP in blood effectively
      prevents formation of classical pathway C3 convertase in the fluid phase.
      Although deposition of additional C3b molecules is necessary to convert a C3
      convertase to a high affinity C5 convertase, the additional C3b molecules play no
      role in the regulation of C5 convertase by C4BP.

PMID- 16979241
TI  - Spatial analysis of American Visceral Leishmaniasis in Mato Grosso do Sul State,
      Central Brazil.
AB  - OBJECTIVES: To map American Visceral Leishmaniasis (AVL) in Mato Grosso do Sul
      State (Central Brazil). METHODS: The distribution of AVL was mapped, using the
      Geographic Information System. RESULTS: The disease was endemic to the Corumba
      Region from 1913 to 1998. Spatial and temporal analysis indicated that the
      expansion route and dissemination through the State of the disease has been from
      west to east, coinciding with three different human interventions; two of them, a
      federal highway and a rail-road, were constructed in the early twentieth century,
      from east to west, from Bauru city, in Sao Paulo State, to Corumba city, in Mato
      Grosso do Sul State. The third anthropogenic intervention was the construction of
      a gas pipeline that started in 1998, and attracted thousands of workers. This
      construction route has the same direction, west to east, and timescale as the
      observed expansion and dissemination of AVL. CONCLUSIONS: The results relate the
      expansion of the disease to intense human traffic along the route of spread.

PMID- 16979242
TI  - A system for receptor functional analysis based on c-fos mRNA expression:
      analysis of GnRH receptors as a test system.
AB  - This report describes the establishment of a system for assessing receptor
      activation by RT-PCR-based detection of c-fos mRNA induction. In this system, COS
      7 cells were transiently transfected with GnRH receptor expression plasmid, and
      ligand-induced c-fos expression was quantified by the RT-competitive PCR method.
      The results were compared with those of a conventional inositol phosphate (IP)
      assay. Changes in c-fos expression levels were observed in a dose- and ligand
      dependent manner. Similar tendencies were observed in ligand selectivity between
      c-fos expression and IP production. The novel system developed and established in
      the present study is sensitive by using RT-PCR and convenient because it requires
      only basic methods of cell culture and molecular biology. It also has the merit
      that it does not need any specific measuring devices or radioactive substances.
      Given the ability of c-fos to respond to diverse stimuli, the present system may
      be applicable for various receptors for bioactive substances in addition to GnRH
      receptor, and useful for various purposes including screening ligands for orphan
      receptors.

PMID- 16979243
TI  - Changes in plasma cholesterol in mood disorder patients: does treatment make a
      difference?
AB  - OBJECTIVES: To examine the impact of treatment in patients with acute episodes of
      major depressive (MD) and manic or hypomanic (M/HM) episodes and co-morbid
      generalized anxiety symptoms, on the total cholesterol blood levels (TC). METHOD:
      A consenting series of patients with acute episodes of DSM IV-R confirmed
      diagnosis of MD or M/H were included. Subjects were treated with antidepressants,
      mood stabilizers, or both. The Hamilton depression scale (HAM-D21), the modified
      mania rating scale (MMRS), and the Hamilton anxiety scale (HAM-A) were utilized
      to evaluate clinical symptoms. Blood samples were drawn for TC estimations after
      10 h of fasting on two occasions over time. The first sample was taken before
      treatment was started, and the second 4 weeks after treatment. The relationship
      between changes in TC and the severity of psychiatric symptoms, as measured on
      HAM-D, MMRS, and the HAM-A, were analysed. RESULTS: 56 subjects (34 with MD and
      22 with M/HM episodes) completed the study. About 4 weeks after treatment there
      was a statistically significant increase in the TC in patients with MD versus a
      significant decrease in patients with M/HM episodes. CONCLUSION: Our results
      replicate earlier reports of significant increase in the cholesterol levels in
      depressed patients after treatment. We report a significant decrease of TC levels
      in M/HM episodes with treatment. Although the results in previous reports and in
      our study are statistically significant, their clinical significance requires
      further examination in longer-term studies.

PMID- 16979244
TI  - Diagnostic variability for schizophrenia and major depression in a large public
      mental health care system dataset.
AB  - Administrative datasets can provide information about mental health treatment in
      real world settings; however, an important limitation in using these datasets is
      the uncertainty regarding psychiatric diagnosis. To better understand the
      psychiatric diagnoses, we investigated the diagnostic variability of
      schizophrenia and major depression in a large public mental health system. Using
      schizophrenia and major depression as the two comparison diagnoses, we compared
      the variability of diagnoses assigned to patients with one recorded diagnosis of
      schizophrenia or major depression. In addition, for both of these diagnoses, the
      diagnostic variability was compared across seven types of treatment settings.
      Statistical analyses were conducted using t tests for continuous data and chi
      square tests for categorical data. We found that schizophrenia had greater
      diagnostic variability than major depression (31% vs. 43%). For both
      schizophrenia and major depression, variability was significantly higher in jail
      and the emergency psychiatric unit than in inpatient or outpatient settings.
      These findings demonstrate that the variability of psychiatric diagnoses recorded
      in the administrative dataset of a large public mental health system varies by
      diagnosis and by treatment setting. Further research is needed to clarify the
      relationship between psychiatric diagnosis, diagnostic variability and treatment
      setting.

PMID- 16979245
TI  - Public beliefs about the causes of mental disorders revisited.
AB  - When the lay public is asked to prioritize their causal beliefs for a vignette
      depicting either schizophrenia or depression, psychosocial causes are most
      popular for depression, but a large proportion of respondents prefers biological
      causes for schizophrenia. Recognition of the vignette as mental illness enhances
      the likelihood to endorse brain disease as a cause and reduces choices of certain
      psychosocial causes.

PMID- 16979246
TI  - Distribution of CCR3 mRNA expression in horse tissues.
AB  - CCL11 (also known as eotaxin) is a very potent and selective mediator of
      eosinophil migration which exerts its effects through its receptor, CCR3. In this
      study we report the cloning of an equine CCR3 cDNA sequence and investigation of
      the localization of CCR3 mRNA expression in horse tissues. Equine CCR3 displayed
      high levels of sequence identity with CCR3 sequences in other species. RT-PCR
      analysis revealed the expression of CCR3 in colon, lung and spleen of normal
      horses. In situ hybridisation experiments indicated that expression of CCR3 mRNA
      in colon was predominantly in eosinophils and to a lesser extent in mast cells,
      whereas CCR3 was seen mainly in lymphocytes of the lung and spleen. In view of
      the role of CCR3 in the recruitment of cells into sites of allergic inflammation,
      equine-specific CCR3 sequence data and information on tissue localization will be
      of potential benefit in the development of CCR3-targeted anti-inflammatory
      therapies in the horse.

PMID- 16979247
TI  - Spatial cognition based on geometry and landmarks in the domestic chick (Gallus
      gallus).
AB  - Recent evidence suggest that encoding of spatial information based on extended
      surfaces may differ from encoding based on discrete arrays of local elements.
      Here we investigated the use of these different frames of reference in domestic
      chicks. Chicks were trained to search for food hidden under sawdust in the center
      of the floor of a square-shaped landmark array, with its center in coincidence
      with the center of a square-shaped enclosure. Displacement of the array to a
      corner caused a shift of searching behavior toward the array, the search activity
      spanning between the center of the arena and the center of the array. After
      changing distances between landmarks, chicks still searched in the central area.
      Asymmetries were apparent in chicks tested in monocular conditions, with left
      eyed chicks being more affected by the overall enclosure and right-eyed chicks by
      local landmarks. These results suggest that chicks can use both distances from
      extended surfaces and local information provided by the landmarks of the array to
      orient in space. However, chicks do not seem to perceive the array as a whole
      configuration, rather they tend to rely only on single landmarks to locate the
      goal.

PMID- 16979248
TI  - Evaluation of IFN-gamma effects on apoptosis and gene expression in neuroblastoma
      -preclinical studies.
AB  - Loss of caspase-8 expression and resistance to cytotoxic agents occurs frequently
      in late stage neuroblastoma (NB). Interferon-gamma (IFN-gamma) induces caspase-8
      in NB cells, sensitizing them to death receptor mediated apoptosis. This study
      characterizes the kinetics of this phenomenon and examines the effects of IFN
      gamma on global gene expression to determine whether IFN-gamma responses are
      achievable at physiologically relevant doses and to define the biological effects
      of this cytokine. Here we examine the IFN-gamma responses of 16 NB cell lines. A
      single <5-min exposure to IFN-gamma (0.5 ng/ml) induced caspase-8 expression in
      all non-expressing cell lines and in 3/6 cell lines which already expressed high
      caspase-8. This increase in caspase-8 proteins was observed within 16 h and
      persisted for up to 9 days. Furthermore, IFN-gamma pretreatment of NB cells
      increased doxorubicin-induced apoptosis nearly 3-fold. Microarray analysis was
      used to identify additional genes involved in proliferation, signaling and
      apoptosis whose expression was modulated via IFN-gamma. Altered expression of
      these genes should further enhance the responsiveness of NB cells to
      chemotherapeutics. Thus, the use of IFN-gamma to sensitize NB cells to cytotoxic
      agents represents an attractive therapeutic strategy and warrants further
      investigation.

PMID- 16979249
TI  - Stimulation of tPA-dependent provisional extracellular fibrin matrix degradation
      by human recombinant soluble melanotransferrin.
AB  - Tissue-type plasminogen activator (tPA) and its substrate plasminogen (Plg) are
      key components in the fibrinolytic system. We have recently demonstrated, that
      truncated human recombinant soluble melanotransferrin (sMTf) could stimulate the
      activation of Plg by urokinase plasminogen activator and inhibit angiogenesis.
      Since various angiogenesis inhibitors were shown to stimulate tPA-mediated
      plasminogen activation, we examined the effects of sMTf on tPA-dependent
      fibrinolysis. This study demonstrated that sMTf enhanced tPA-activation of Plg by
      6-fold. sMTf also increased the release of [125I]-fibrin fragments by tPA
      activated plasmin. Moreover, we observed that the interaction of sMTf with Plg
      provoked a change in the fibrin clot structure by cleaving the fibrin alpha and
      beta chains. Overall, the present study shows that sMTf modulates tPA-dependent
      fibrinolysis by modifying the clot structure. These results also suggest that
      sMTf properties could involve enhanced dissolution of the provisional
      extracellular fibrin matrix.

PMID- 16979250
TI  - Partial evidence of an association between epidermal growth factor A61G
      polymorphism and age at onset in male schizophrenia.
AB  - Epidermal growth factor (EGF) is a well-known neurotrophic factor regulating the
      development of various neuronal cells, including dopaminergic neurons, and
      dysfunction of EGF signals has been demonstrated as a risk factor for
      schizophrenia. Recently, several researchers have investigated associations
      including age at onset (AAO) with EGF A61G functional polymorphism, but the
      results of these studies have been controversial. Thus, we investigated whether
      A61G plays a role in predisposition to schizophrenia and its effects on AAO. Our
      subjects included 190 patients with schizophrenia and 347 controls. We assessed
      three different points of AAO: age at first occurrence of positive psychotic
      symptoms, medication, and hospitalization as a patient with schizophrenia. We
      found no differences in allele and genotype frequencies between patients and
      controls or associations between A61G and AAOs across stratified points in the
      entire sample and in each gender. However, we found significant gender
      differences in patients with the AA genotype in all stratified points of AAOs.
      Subset analyses of G allele distribution between clinical subsets with an AAO
      cutoff of 20 years revealed that male patients with early onset schizophrenia
      were more likely to exhibit the common AA homozygote than male patients with
      adulthood onset schizophrenia. In conclusion, although we were unable to support
      an association between EGF A61G and schizophrenia, the AA genotype might play a
      disease-modifying role differentially according to gender.

PMID- 16979251
TI  - Prevalence of Arcobacter and Campylobacter on broiler carcasses during
      processing.
AB  - Broiler carcasses (n=325) were sampled in a U.S. commercial poultry processing
      plant for the prevalence of Arcobacter and Campylobacter at three sites along the
      processing line: pre-scald, pre-chill and post-chill. Samples (75-125 broilers
      per site) were collected during five plant visits from August to October of 2004.
      Arcobacter was recovered from pre-scald carcasses more frequently (96.8%) than
      from pre-chill (61.3%) and post-chill carcasses (9.6%). Campylobacter was
      isolated from 92% of pre-scald carcasses, 100% of pre-chill carcasses, and 52% of
      post-chill carcasses. In total, Arcobacter was isolated from 55.1% (179 of 325),
      while Campylobacter was isolated from 78.5% (255 of 325) of the carcasses from
      the three collection sites. For Arcobacter identification, a species-specific
      multiplex PCR showed that A. butzleri was the most prevalent species (79.1%)
      followed by A. cryaerophilus 1B (18.6%). A. cryaerophilus 1A was found at low
      levels (2.3%). PCR identified the most common Campylobacter species as C. jejuni
      (87.6%) followed by C. coli (12.4%). Overall, significant contamination of
      broiler carcasses by Arcobacter was observed, although less than that found for
      Campylobacter. From pre-scald to post-chill, a far greater reduction in
      Arcobacter numbers was observed than for Campylobacter. Our results for
      Arcobacter, obtained from the same environment as the closely related pathogen
      Campylobacter, will aid in the development of control measures for this emerging
      pathogen.

PMID- 16979252
TI  - Recombinant mussel adhesive protein Mgfp-5 as cell adhesion biomaterial.
AB  - Mytilus galloprovincialis foot protein type-5 (Mgfp-5) is one of the mussel
      adhesive proteins that participate in adhesion with the substratum. We previously
      reported the production of recombinant Mgfp-5 in Escherichia coli and showed that
      the recombinant protein had superior adhesion abilities versus those of Cell-Tak,
      a commercially available mussel adhesive protein mixture. In the present work, we
      investigated the feasibility of using recombinant Mgfp-5 as a cell adhesion
      agent. Purified and tyrosinase-modified recombinant Mgfp-5 was used to adhere
      living anchorage-independent cells such as insect Drosophila S2 cells and human
      MOLT-4 cells onto glass slides. Our results revealed that these cell lines
      efficiently attached to recombinant Mgfp-5-coated glass surfaces, and that
      surface-immobilized S2 cells were viable and able to undergo cell division for up
      to 1 week. Cytochemical studies with 4',6-diamidino-2-phenylindole (DAPI)
      staining of nuclei and immunofluorescence for secreted foreign human
      erythropoietin (hEPO) from recombinant S2 cells and quantitative comparative
      analyses of S2 cell binding ability with Cell-Tak and poly-L-lysine, the main
      cell adhesion agent, were performed to demonstrate successful usage of
      recombinant Mgfp-5 for cell biological applications. Collectively, these results
      indicate that recombinant Mgfp-5 may be a useful new cell adhesion biomaterial
      for anchorage-independent cells.

PMID- 16979253
TI  - A HIV-2-based self-inactivating vector for enhanced gene transduction.
AB  - The employment of HIV-1-based vectors in clinical trials is controversial mainly
      due to the lethal nature of the virus. HIV-2 is less pathogenic in nature and
      therefore is likely to be safer for vector design and production. We developed
      HIV-2-based self-inactivating vectors in which 520 bp out of 554 bp of the viral
      U3 was deleted. Interestingly, high titers were obtained only when an exogenous
      promoter was used to drive expression of viral RNA. It was found that the vectors
      could target a wide range of mammalian cell types including primary neuronal
      cells and could yield long term expression. It is also noteworthy that the HIV-2
      vectors could be effectively cross-packaged into HIV-1 core, which might provide
      for enhanced safety by reducing the recombination potential of the system.

PMID- 16979254
TI  - Inhibition of hepatitis C virus gene expression by small interfering RNAs using a
      tri-cistronic full-length viral replicon and a transient mouse model.
AB  - HCV is an ideal target for siRNA as its genome, a single-stranded RNA, is
      translated into a single viral polyprotein and replicated into negative-stranded
      RNA. In the present study, we monitored the effects of 36 different small
      interfering RNAs (siRNAs) transcribed from a plasmid-derived expression system on
      the luciferase activities expressed from a full-length HCV replicon, to identify
      potent siRNA target sites. Delivery of nine selected siRNA expression vectors
      into human hepatoma cells (Huh7) carrying a genomic HCV replicon resulted in a
      significant reduction in viral protein and RNA levels. Moreover, synthetic siRNAs
      directed to target sites (core, NS3, NS4A and NS4B coding regions) in the HCV
      genome efficiently suppressed viral replication in a dose-dependent manner. A
      transient mouse model system expressing viral structural proteins in the liver
      was constructed using the hydrodynamic transfection method to confirm in vivo
      anti-HCV activity of the selected siRNAs. A 21-nucleotide siRNA, which can
      hybridize to the HCV core coding region with a single G-U base pair, suppressed
      weakly transgene expression in mice. However, this anti-viral effect was enhanced
      upon substitution with a 27-mer duplex RNA. Our results will provide useful
      information about designing potent siRNAs against variable target sites.

PMID- 16979255
TI  - Evaluation of the superiority of insulin glargine as basal insulin replacement by
      continuous glucose monitoring system.
AB  - To evaluate the superiority of insulin glargine as basal insulin replacement by
      continuous glucose monitoring system (CGMS). Twenty-four patients with type 2
      diabetes mellitus (T2DM) whose blood glucose was not well controlled with
      sulphanylureas were enrolled. At first, they were treated with extended-release
      glipizide (glucotrol XL) 5mg/d before breakfast for 2 weeks, then randomized to
      combination treatment with glargine (16 patients) or NPH (8 patients) and treated
      for 12 weeks. CGMS were carried in the second week after treatment with glucotrol
      XL, and in the 12th week after combination treatment. The data of CGMS showed:
      (1) When FPG were well controlled in both groups (glargine group versus NPH
      group: 6.0+/-1.0 mmol/L versus 5.8+/-1.3 mmol/L), the blood glucose level at 3:00
      a.m. (5.1+/-0.9 mmol/L versus 4.2+/-0.8 mmol/L) were higher (P<0.05), TPG< or
      =3.0 mmol/L at night were lower (2.56+/-1.79 versus 5.88+/-1.96), and the rate of
      nocturnal hypoglycemia (1/16 versus 4/8) were less (P=0.028) in glargine group
      than those in NPH group. (2) CGMS showed that the daily blood glucose profile
      excursion were more smoother in glargine group than those in NPH group. In
      conclusion, it was confirmed with CGMS that compared with traditionally basal
      insulin replacement with NPH, the combination treatment with glargine injection
      at bedtime may be predominant for stabilizing the daily blood glucose profile
      excursion and decreasing the nocturnal hypoglycemia events incidence. So glargine
      may be a more ideal basal insulin replacement than NPH.

PMID- 16979256
TI  - Dense deformation field estimation for atlas-based segmentation of pathological
      MR brain images.
AB  - Atlas registration is a recognized paradigm for the automatic segmentation of
      normal MR brain images. Unfortunately, atlas-based segmentation has been of
      limited use in presence of large space-occupying lesions. In fact, brain
      deformations induced by such lesions are added to normal anatomical variability
      and they may dramatically shift and deform anatomically or functionally important
      brain structures. In this work, we chose to focus on the problem of inter-subject
      registration of MR images with large tumors, inducing a significant shift of
      surrounding anatomical structures. First, a brief survey of the existing methods
      that have been proposed to deal with this problem is presented. This introduces
      the discussion about the requirements and desirable properties that we consider
      necessary to be fulfilled by a registration method in this context: To have a
      dense and smooth deformation field and a model of lesion growth, to model
      different deformability for some structures, to introduce more prior knowledge,
      and to use voxel-based features with a similarity measure robust to intensity
      differences. In a second part of this work, we propose a new approach that
      overcomes some of the main limitations of the existing techniques while complying
      with most of the desired requirements above. Our algorithm combines the
      mathematical framework for computing a variational flow proposed by Hermosillo et
      al. [G. Hermosillo, C. Chefd'Hotel, O. Faugeras, A variational approach to multi
      modal image matching, Tech. Rep., INRIA (February 2001).] with the radial lesion
      growth pattern presented by Bach et al. [M. Bach Cuadra, C. Pollo, A. Bardera, O.
      Cuisenaire, J.-G. Villemure, J.-Ph. Thiran, Atlas-based segmentation of
      pathological MR brain images using a model of lesion growth, IEEE Trans. Med.
      Imag. 23 (10) (2004) 1301-1314.]. Results on patients with a meningioma are
      visually assessed and compared to those obtained with the most similar method
      from the state-of-the-art.

PMID- 16979257
TI  - How novel are urban ecosystems?

PMID- 16979258
TI  - Is it time for urban ecology to include the marine realm?

PMID- 16979259
TI  - Robust preference for a flavor paired with intragastric glucose acquired in a
      single trial.
AB  - Rats learn to prefer flavors followed by postingestive action of nutrients. This
      experiment demonstrates that such preferences can be acquired with only a single,
      brief pairing of a novel flavor with intragastric (IG) glucose infusion. Male
      rats with IG catheters consumed unflavored saccharin in daily 10-min sessions,
      and then received in counterbalanced order on separate days a single pairing of
      coffee- or vinegar-flavored saccharin with IG glucose, and of the opposite flavor
      with IG water. Rats subsequently preferred the glucose-paired flavor in a choice
      test in the absence of glucose infusion. Preference was robust, persisting
      through repeated non-reinforced testing.

PMID- 16979260
TI  - How much do medical students know about infection control?
AB  - Changes in undergraduate medical training mean that students have direct patient
      contact from an early stage of their training. This study aimed to assess the
      knowledge of third-year medical students at the University of Birmingham Medical
      School, UK on infection control policy and procedures. A semi-structured
      questionnaire was distributed to medical students. Out of 322 students, 156
      returned completed questionnaires (48%). Results showed that 58% of medical
      students did not know the correct indications for using alcoholic hand gel, 35%
      did not know the correct use of gloves, and 50% did not know the exclusion period
      after an episode of diarrhoea and vomiting. Sixty-four percent of medical
      students reported formal teaching on hand hygiene, 12% reported informal
      teaching, 19% reported both types of teaching and 5% reported no hand hygiene
      teaching at all. Forty-nine percent of medical students thought that there was
      insufficient emphasis on infection control in their course. These results raised
      concerns about medical students' knowledge about infection control. The
      University is currently reviewing the need for a more structured model for the
      teaching and assessment of infection control.

PMID- 16979261
TI  - Where to draw the line? When must the planning stop and the building begin?

PMID- 16979262
TI  - Lowbury Lecture 2005: infection control from a global perspective.
AB  - All healthcare settings around the world face the problem of healthcare
      associated infections (HCAIs). Rates of infection vary between countries and
      within the same country depending on resources, interest of caregivers and
      healthcare staff, and patients' socio-economic situation. According to recent
      publications, 10-70% of HCAIs are preventable. Failure to comply with guidelines
      on hand hygiene, glove and gown use, and barrier nursing is a problem and
      unnecessary infection control measures are costly. National legislations and
      regional, national and international standards and guidelines associated with
      infection control also have an impact for countries that are not directly
      involved. They should be based on the assessment of infection risk, and should
      not increase costs unnecessarily. The International Federation of Infection
      Control and national infection control societies play an important role in
      continuing the education of infection control specialists.

PMID- 16979263
TI  - Use of nasal mupirocin for eradicating meticillin-resistant Staphylococcus
      aureus: a dilemma?

PMID- 16979264
TI  - Pay for performance in emergency medicine.
AB  - One of the latest market-based solutions to the rising costs and quality gaps in
      health care is pay for performance. Pay for performance is the use of financial
      incentives to promote the delivery of designated standards of care. Pay for
      performance represents a dramatic change in the reimbursement of providers, from
      fixed rates or fees, to variable compensation based on the quality of care. This
      article serves as an introduction to pay for performance. I discuss the goals and
      structure of pay for performance plans and their limitations and potential
      consequences in the health care arena. A particular focus is provided on pay-for
      performance initiatives affecting the emergency department either directly by
      contracting at the group level or indirectly through hospital reward programs. I
      also provide a strategy to guide constructive engagement by emergency physicians
      in the pay-for-performance movement.

PMID- 16979265
TI  - Art, Chaos, Ethics, and Science (ACES): a doctoring curriculum for emergency
      medicine.
AB  - ACES (Art, Chaos, Ethics, and Science) is a curriculum developed by 2 residents
      and a faculty mentor at the Denver Health Medical Center Emergency Medicine
      Residency Program. The goal of the ACES curriculum is 2-fold: (1) to discuss
      areas of clinical consequence typically outside the scope of the regular academic
      curriculum, such as ethical dilemmas and the challenges of professionalism; and
      (2) to encourage reflection on our roles as caregivers on a personal, public
      health, and political level. Each bimonthly "doctoring roundtable" session
      focuses on one of these goals, bringing local and national leaders in the field
      to the forum to enrich discussion. Attending physicians from academic and private
      settings within the residency, residents at all levels, rotating medical
      students, and, for the past year, emergency department nurses participate in the
      meetings. Thus far, regular voluntary participation has been the only measure of
      the ongoing program's success. In this descriptive article, we discuss the aim of
      the program, the curriculum, and how the ACES program enriches the residency's
      educational goals. Recent accreditation requirements for residency training
      programs mandate educational experiences that allow residents to demonstrate
      competency in professionalism and ethical principles. The ACES curriculum
      developed a unique niche in our residency, creating an open forum for passionate
      discussion of challenging clinical encounters, unpressured reflection on ethics
      and decisionmaking, and constructive personal and professional development.

PMID- 16979266
TI  - K(ATP)-dependent neurotransmitter release in the neuronal network of the rat
      caudate nucleus.
AB  - K(ATP) channels can couple the bioenergetic metabolism of the cell to membrane
      excitability. Here, we show gamma-aminobutyric acid (GABA) mediated inhibition of
      dopamine outflow from slices of the rat caudate nucleus that is regulated by
      extracellular glucose via high- and low-affinity K(ATP) channels. During glucose
      reduction, a biphasic dopamine effect could be observed with first a dopamine
      increase followed by a decline at low glucose concentrations. Both phases were
      inhibited by glibenclamide. Pinacidil decreased DA outflow without an effect of
      glucose reduction implying an overall activation of K(ATP) channels. The first
      phase with dopamine increase was related to reduced GABAergic activity and could
      be blocked by bicuculline. Our results may be explained by different types of
      K(ATP) channels with low affinity of ATP and glibenclamide on inhibitory
      GABAergic and high-affinity on excitatory DAergic neurons. This led us to suggest
      a biological principle through which neuronal networks are functioning.

PMID- 16979267
TI  - No association of chromatin-modifying protein 2B with sporadic frontotemporal
      dementia.
AB  - Mutations of the chromatin modifying protein 2B gene (CHMP2B) were identified, in
      a Danish pedigree, to cause familial frontotemporal dementia (FTD). To explore
      the possible genetic contribution of common CHMP2B variants in sporadic FTD, we
      analyzed 14 single nucleotide polymorphisms covering the entire genomic region of
      CHMP2B. After adjustment for multiple testing single marker and haplotype
      analysis revealed no significant association with sporadic FTD. Thus, we conclude
      that CHMP2B can be excluded as a susceptibility gene conferring risk to sporadic
      forms of FTD.

PMID- 16979268
TI  - Anatomical and functional alterations in semantic dementia: a voxel-based MRI and
      PET study.
AB  - Rare studies have used magnetic resonance imaging (MRI) and voxel-based
      morphometry (VBM) to assess atrophy, and only two positron emission tomography
      (PET) studies used SPM to examine functional changes in semantic dementia (SD).
      Our aim was to highlight both morphological and functional abnormalities in a
      same group of 10 SD patients, in the entire brain, using a "state of the art"
      methodology (optimized VBM procedure, PET data corrected for partial volume
      effects and voxel-based analyses). We also used an extensive neuropsychological
      battery. We showed that main alterations concerned the left temporal lobe, in
      accordance with the striking impairment of semantic memory in SD patients, as
      well as the hippocampal region, which may partly explain their moderate episodic
      memory deficits. Hypometabolism was more extensive than grey matter loss in both
      temporal lobes, and specifically concerned the orbitofrontal areas, consistent
      with the moderate impairment of executive functions and behavioural changes.
      While PET is more sensitive than MRI, there is striking concordance between
      morphological and functional abnormalities, which contrasts with the discordance
      observed in Alzheimer's disease and might be a typical feature of SD.

PMID- 16979269
TI  - [Thoracic infectious aortitis: microbiology, pathophysiology and treatment].
AB  - BACKGROUND: Thoracic infectious aortitis are currently rare. They are always
      lethal without any treatment. The microorganisms involved are numerous with
      particular pathophysiological characteristics for each bacterium. Treatment is
      difficult and must associate medical and surgical care. RECENT FINDINGS:
      Bacterial epidemiology of infectious aortitis has been profoundly modified with
      the large use of antibiotics. Syphilitic aortitis were frequent in the beginning
      of the twentieth century but its incidence has dramatically fallen. It still
      exists and its clinical presentation must be known to begin an adequate
      treatment. Other bacterial aetiologies of these aortitis are more classical with
      high frequencies of Staphylococcus aureus and Streptococcus, which are often
      associated with infective endocarditis. Among Gram-negative bacteria, Salmonella
      spp are the most frequently met microorganisms. Atherosclerosis represents the
      principal risk factor of these infectious aortitis. It provokes arterial parietal
      damage useful for bacterial attach. A saccular aneurysm of infective origin can
      then appear. Treatment must consist on antibiotics before surgery; Tuberculous
      aortitis are also possible but are much more rare. CONCLUSION: Thoracic
      infectious aortitis are very rare but must be known because of their poor
      prognosis. Treatment is difficult and prevention of atherosclerosis which is the
      most important risk factor of these diseases is therefore of greatest importance.

PMID- 16979270
TI  - A review on the mechanical quality of articular cartilage - implications for the
      diagnosis of osteoarthritis.
AB  - The functional behaviour of articular cartilage in diarthrodial joints is
      determined by its morphological and biomechanical properties. Whereas
      morphological changes are mainly detectable in the progressed stages of
      osteoarthritis, biomechanical properties seem to be more sensitive to early
      degenerative variations since they are determined by the biochemical composition
      and structural arrangement of the extracellular matrix. The objective of this
      paper is to review studies focussing on variations in the mechanical compressive
      properties during the early pre-osteoarthritic stage. The aim is to quantify the
      requirements to detect the early cartilage degeneration in pre-osteoarthritis
      based on the mechanical parameters and to create an updated basis for a better
      understanding of inherent relationships between characteristic parameters in
      articular cartilage. Correlations between mechanical and biochemical parameters
      as well as magnetic resonance, ultrasonic, histological and structural parameters
      were observed. In early osteoarthritis, static moduli decrease below 80% of
      healthy controls and dynamic moduli below 30% of controls. To identify
      osteoarthritic changes of articular cartilage based on static or dynamic
      mechanical parameters in an early stage of the disease progression the accuracy
      of a mechanical testing method has to be adequate to detect changes of 10% in
      cartilage stiffness.

PMID- 16979271
TI  - Surface electromyography activity of trunk muscles during wheelchair propulsion.
AB  - BACKGROUND: Trunk instability due to paralysis can have adverse effects on
      posture and function in a wheelchair. The purpose of this study was to record
      trunk muscle recruitment patterns using surface electromyography from unimpaired
      individuals during wheelchair propulsion under various propulsion speed
      conditions to be able to design trunk muscle stimulation patterns for actual
      wheelchair users with spinal cord injury. METHODS: Fourteen unimpaired subjects
      propelled a test wheelchair on a dynamometer system at two steady state speeds of
      0.9 m/s and 1.8 m/s and acceleration from rest to their maximum speed. Lower
      back/abdominal surface electromyography and upper body movements were recorded
      for each trial. Based on the hand movement during propulsion, the propulsive
      cycle was further divided into five stages to describe the activation patterns.
      FINDINGS: Both abdominal and back muscle groups revealed significantly higher
      activation at early push and pre-push stages when compared to the other three
      stages of the propulsion phase. With increasing propulsive speed, trunk muscles
      showed increased activation (P<0.0001). Back muscle activity was significantly
      higher than abdominal muscle activity across the three speed conditions
      (P<0.0005), with lower back muscles predominating. INTERPRETATION: Abdominal and
      back muscle groups cocontracted at late recovery phase and early push phase to
      provide sufficient trunk stability to meet the demands of propulsion. This study
      provides an indication of the amount and duration of stimulation needed for a
      future application of electrical stimulation of the trunk musculature for persons
      with spinal cord injury.

PMID- 16979272
TI  - Interception of residual nitrate from a calcareous alluvial soil profile on the
      North China Plain by deep-rooted crops: a 15N tracer study.
AB  - 15N-labeled nitrate was injected into different depths of an alluvial calcareous
      soil profile on the North China Plain. Subsequent movement of NO3- -N and its
      recovery by deep-rooted maize (Zea mays L.) and shallow-rooted eggplant (Solanum
      melongena L.) were studied. Under conventional water and nutrient management the
      mean recoveries of 15N-labeled nitrate from K(15)NO3 injected at depths 15, 45,
      and 75 cm were 22.4, 13.8, and 7.8% by maize and 7.9, 4.9, and 2.7% by eggplant.
      The recovery rate by maize at each soil depth was significantly higher than by
      eggplant. The deeper the injection of nitrate the smaller the distance of its
      downward movement and this corresponded with the movement of soil water during
      crop growth. Deeper rooting crops with high root length density and high water
      consumption may therefore be grown to utilize high concentrations of residual
      nitrate in the subsoil from previous intensive cropping and to protect the
      environment.

PMID- 16979273
TI  - Prokaryotic life in a potash-polluted marsh with emphasis on N-metabolizing
      microorganisms.
AB  - Prokaryotic life along the salt gradient of the potash marsh resulting from
      mining waste at Schreyahn, Northern Germany, was screened for the distribution of
      total prokaryote (assessed by the 16S rRNA gene) and of N2-fixing (nifH gene),
      denitrifying (nosZ) and nitrifying (amoA) microorganisms. Information on
      prokaryotes was retrieved from the different soil sites (a) by culturing in
      conventional media, (b) by isolating the DNA, amplifying the target genes by PCR
      followed by sequencing, (c) by employing the recently developed computer program
      (TReFID [Rosch, C., Bothe, H., 2005. Improved assessment of denitrifying, N2
      fixing, and total-community bacteria by terminal restriction fragment length
      polymorphism analysis using multiple restriction enzymes. Applied and
      Environmental Microbiology 71, 2026-2035]) based on tRFLP data. New sequences
      were obtained as well as ones that were almost identical to those found at far
      distant locations. Whereas the distribution of plants strictly follows the salt
      gradient, this is apparently not the case with prokaryotes. Bacteria of
      hypersaline areas coexist with salt-non-tolerant species. The recently developed
      TReFID program is successfully applied to characterize a prokaryote community
      structure.

PMID- 16979274
TI  - Protecting children from the dangers of urban poverty.
AB  - Exposure to the social ecology of poor urban neighborhoods significantly
      increases the incidence of traumatic stress disorders, placing children growing
      up in such neighborhoods at disproportionate risk. Although the risk factors for
      and effects of childhood complex traumatic stress disorders are well documented,
      there is little intervention research to guide the delivery of services to this
      population. This paper builds on current knowledge of childhood trauma and
      related treatments by introducing an intervention model using constructive family
      ritual functioning as a mechanism for increasing the protective function of the
      family. The intervention model postulates that use of family rituals as a coping
      resource will lead to decreased symptoms of chronic traumatic stress and rates of
      exposure to additional trauma.

PMID- 16979275
TI  - Association between the tryptophan hydroxylase-1 gene A218C polymorphism and
      citalopram antidepressant response in a Korean population.
AB  - Tryptophan hydroxylase-1 (TPH1) is the rate-limiting enzyme in serotonin
      biosynthesis, and selective serotonin reuptake inhibitors (SSRIs) exert their
      activity enhancing the general serotonergic tone. Citalopram is the most
      selective SSRI, with little or no affinity for a variety of receptor types. The
      goal of this study was to investigate whether the A218C polymorphism of the TPH1
      gene is associated with the citalopram antidepressant response in subjects with
      major depressive disorder (MDD). All of the patients were evaluated using the 21
      item Hamilton Depression Rating Scale before beginning and after 8 weeks of
      citalopram treatment. Genotyping was performed with the polymerase chain
      reaction. The remission rate to citalopram treatment was worse in MDD subjects
      with the TPH1 A/A and A/C genotypes than in those with the TPH1 C/C genotype. Our
      results suggest that the A218C polymorphism of the TPH1 gene serves as a
      modulator of antidepressant activity, especially in terms of treatment remission.

PMID- 16979276
TI  - Risk assessment and food allergy: the probabilistic model applied to allergens.
AB  - In order to assess the risk of unintended exposure to food allergens, traditional
      deterministic risk assessment is usually applied, leading to inconsequential
      conclusions as 'an allergic reaction cannot be excluded'. TNO therefore developed
      a quantitative risk assessment model for allergens based on probabilistic
      techniques resulting in a more exhaustive risk assessment and more detailed
      information. By now, this approach is recognized as the future approach in
      allergen risk assessment. A case study (hazelnut proteins in chocolate spread) is
      presented as a proof of concept.

PMID- 16979277
TI  - Antigenotoxic effect of Saccharomyces cerevisiae on the damage produced in mice
      fed with aflatoxin B(1) contaminated corn.
AB  - The potential of Saccharomyces cerevisiae (Sc) was evaluated for reducing the
      micronucleated normochromatic erythrocytes (MNNE) rate in mice fed AFB(1)
      contaminated corn. The study included two groups fed AFB(1) contaminated corn
      (0.4 and 0.8 mg/kg), a control fed uncontaminated corn, another group fed
      uncontaminated corn and 0.3% of Sc (1 x 10(8) live cells/g), and two groups fed
      AFB(1) contaminated corn (0.4 and 0.8 mg/kg) plus 0.3% Sc. Weight and MNNE were
      determined weekly for six weeks. Subsequently, the same determinations were made
      for another three-week period, but in mice receiving only a normal diet, without
      AFB(1) and Sc. Results in the first period revealed the following: control and Sc
      fed mice had similar constant weight increase, and low MNNE rate; mice fed only
      AFB(1) showed weight decrease and significant MNNE increase; finally, Sc improved
      weight gain and reduced MNNE produced by AFB(1). In the second period, results
      exhibited a tendency similar to that of the previous phase in the control and Sc
      fed mice; the weight and MNNE values improved in the other groups. We also
      determined the capacity of Sc for adsorbing and modifying the mycotoxin
      structure. The mixture was filtered to obtain two phases, and AFB(1) content was
      measured. Sc revealed a potent adsorbent capacity; however, chromatographic
      determination suggested no structural modification.

PMID- 16979278
TI  - Effect of in utero exposure to di-(2-ethylhexyl)phthalate: distribution in the
      rat fetus and testosterone production by rat fetal testis in culture.
AB  - DEHP is known to cause reproductive toxicity in rats, particularly during the
      neonatal period. Pregnant and brood rats were treated by gavage with 750
      mg/kgb.w./day DEHP starting on GD14 within PND4. Two hours after (14)C-DEHP
      administration on GD15, GD18, GD21 and PND4, the radioactivity content was
      measured in the dams blood and in the liver, gonads and carcass of the offspring.
      The radioactivity concentration recovered in the fetuses was one or two order of
      magnitude lower than the concentration found in the dam plasma. A low proportion
      of radioactivity was present in fetal gonads, ca. 2%, 5% and 3.6% on GD18, GD21
      and PND4, respectively. The effect on testosterone production of DEHP and its
      metabolites (MEHP, metabolites VI and IX) was assessed in fetal testis cultures
      using a dose-range which included the maximal exposure observed in vivo. None of
      the compounds affected testosterone production. Thus, DEHP and/or its metabolites
      appear to cross the placental barrier, reach the fetal gonads. In vitro, neither
      DEHP nor its main metabolites decreased the testosterone production.

PMID- 16979279
TI  - Comparative evaluation of the peri-implant bone tissue mineral density around
      unloaded titanium dental implants.
AB  - OBJECTIVE: The mechanical properties of bone are greatly influenced by the
      percentages of organic and mineral constituents. Nevertheless, the information
      about the mineral content on a microscopic scale in peri-implant bone is scarce.
      The aim of this work was to analyze the bone mineral density of peri-implant bone
      under different techniques. DESIGN: Five unloaded titanium dental implants with a
      micro-structured surface (three XiVE plus and two Frialit 2, DENTSPLY-Friadent,
      Mannheim, Germany) were retrieved from the mandible of five patients after a 6
      month period. scanning electron microscopy with backscattered electron signal
      (BSE), light microscopy (LM) with a double staining technique, fluorescence
      microscopy and confocal laser microscopy were used for measuring microscopic
      mineral content variations in peri-implant bone. Histomorphometry and image
      intensity (grey level) were evaluated using a software package for image
      analysis. RESULTS: The low mineral density index (LMDI) for LM was of 29.2+/-3.1
      (mean+/-S.D.), while the high mineral density index (HMDI) was of 88.2+/-3.6
      (mean+/-S.D.). The one-way ANOVA analysis showed a significant difference
      (P<0.001) among the groups. The pairwise Holm-Sidak test identified the
      differences among HMDI indexes for both LM and SEM values and also for cross
      evaluation of the LMDI and HMDI values. The comparison between LMDI indexes for
      both SEM and LM did not show any significance. The fluorescence microscopy
      analysis showed clearly the difference between old (high mineralized) and new
      (low mineralized) bone tissue near the implant surface. Under confocal laser
      microscopy the same sections showed the area of bone modelling closest to implant
      surface. CONCLUSION: In this study it was found that bone around unloaded
      implants showed a low mineral density index under all the investigation methods
      used. It was also found that the conventional LM technique with the double
      staining method was able to intensely stain the bone area with a low mineral
      content.

PMID- 16979280
TI  - The effect of cancer treatment on female fertility and strategies for preserving
      fertility.
AB  - Aggressive chemotherapy and radiotherapy in young patients with cancer has
      greatly enhanced the life expectancy of these patients, but these treatments
      often cause infertility because of the massive destruction of the ovarian reserve
      resulting in premature ovarian failure (POF). This review focuses on the effect
      of cancer treatments on fertility and on the various surgical and assisted
      reproduction innovations that are available to provide the patient with the
      option of future pregnancies. As the emerging discipline of fertility
      preservation is steadily attracting increasing interest, developments in the near
      future promise to be very exciting. However, in everyday routine work, better
      interdisciplinary cooperation between gynecological and pediatric oncologists,
      surgeons, immunologists and endocrinologists is necessary so that individualized
      options for fertility preservation can be offered in advance of surgical
      procedures or cancer treatments. GnRH analog treatment can preserve fertility in
      some patients, but not in all. At present, cryopreservation of ovarian tissue
      appears as a very promising method of providing the cancer patient with a
      realistic chance of preserving fertility-a prospect that is also extremely
      important to patients for psychological reasons.

PMID- 16979281
TI  - Biosorption of heavy metals by activated sludge and their desorption
      characteristics.
AB  - The biosorption of different metals (Cu2+, Cd2+, Zn2+, Ni2+ and Pb2+) was
      investigated using activated sludge. The optimum pH was 4 for Cd, Cu and Pb
      sorption and 5 for Ni and Zn. Biomass metal uptake clearly competed with protons
      present in the aqueous medium, making pH an important variable in the process.
      Protons consumed by biomass in control tests versus protons exchange in
      biosorption tests confirmed a maximum exchange between metal cations and protons
      at pH 2. The study of the influence of biomass concentration revealed that the
      amount of protons released from biomass increased with biomass concentration.
      This would confirm the hypothesis of ion exchange between both types of ions. The
      application of the Langmuir and Freundlich models showed a better fitting of
      experimental data to the first model. The maximum sorption uptake of the studied
      metals by the activated sludge showed the following decreasing order:
      Pb>Cu>CdZn>Ni. Desorption experiments showed that HCl was a good eluent for the
      five metals tested, particularly at low pH values (1 and 2). At pH 3 or 4 the
      desorption yield was significantly lower. However, its use did not allow the
      reuse of biomass in subsequent loading and unloading cycles. EDTA was also a good
      desorption agent, achieving the total recovery for the five metals tested at a
      concentration of 1mM, with the advantage that biomass could be reused for three
      sorption-desorption cycles.

PMID- 16979282
TI  - Estimation of intracellular phosphorus content of phosphorus-accumulating
      organisms at different P:COD feeding ratios.
AB  - The intracellular phosphorus content of phosphorus-accumulating organisms (PAO)
      was determined based on a stoichiometric equation and phosphorus balance for an
      enhanced biological phosphorus removal system fed with different P:COD ratios.
      The data indicated that a higher P:COD feeding ratio could significantly promote
      the growth of PAO. As the P:COD feeding ratio increased from 0.02:1 to 0.04:1 and
      0.16:1, the phosphorus in the sludge increased considerably from 0.053 to 0.084
      and 0.205 mg P (mg VSS(aerobic))(-1), respectively, indicating a dynamic
      condition in the microbial population. From the calculations, the mass fractions
      of the PAO, glycogen-accumulating organisms, and ordinary heterotrophs changed
      from 0.10-0.15, 0.83-0.88, and 0.02 at 0.02:1 to 0.19-0.28, 0.70-0.79, and 0.02
      at 0.04:1 and to 0.478-0.71, 0.26-0.50, 0.03 at 0.16:1 P:COD feeding ratios,
      respectively. Despite the variation in microbial diversity, the calculated
      phosphorus contents of the PAO at all P:COD feeding ratios were consistent
      between 0.241 and 0.378 mg P (mg VSS(PAO))(-1). The initial specific phosphorus
      release and uptake rates were 84.7-167.9 mg P (g VSS(PAO))(-1)h(-1) and 52.8-90.0
      mgP (g VSS(total))(-1)h(-1), respectively.

PMID- 16979284
TI  - Policy and practice in Myanmar's protected area system.
AB  - Myanmar's protected area (PA) system began nearly 150 years ago under royal
      patronage. Park policies and practices, embodied in 19 pieces of legislation
      developed sporadically during and after the colonial period. As a result of the
      FAO-UNDP's Nature Conservation and National Parks Project (1981-1985) the
      government established the Nature & Wildlife Conservation Division and placed it
      within the Forest Department as the agency responsible for PA management. As a
      consequence the number of parks increased from 14 to 33. Myanmar's median park
      size is less than 50 km(2), but only five parks (15%) are larger than 1000 km(2).
      Most parks conserve terrestrial habitats; parks encompassing inland wetlands,
      mangrove, and marine habitats are limited in number and size. Existing PAs
      unequally represent Myanmar's ecosystems; the Malay Transition, Burmese coast,
      Burmese Transition and Cardamom Mountains bio-units are under-represented within
      the system. The effective total PA size (i.e., area of all parks less the area of
      13 paper parks) is currently about 2.1%. Budgetary support for parks increased
      11% since 1996, but is insufficient to address park needs, particularly in remote
      parks that are understaffed. Limited education and training of PA staff is a
      major factor limiting effective park management. Fifty-eight percent of park
      wardens are educated as foresters, and 42% have university degrees. The average
      posting in a park is 4 years, which is less than ideal for management continuity.
      Recommended actions to secure Myanmar's PAs include evaluation and reformulation
      of policies, increasing representation of Myanmar's habitats within the PA
      system, management planning, and standardizing protocols for anti-poaching
      patrols and other forms of law enforcement. Improved leadership training for
      wardens and range forest officers can also improve park management. Funding for
      community relations and more integrated management of parks and people can reduce
      conflicts, while environmental education and outreach activities can provide some
      needed services. Finally, new ways and means are needed to support these
      activities. Myanmar's PAs need creative and sustainable means of support,
      including partnerships with non-government organizations to supplement
      traditional means of support.

PMID- 16979283
TI  - Diffuse pollution loading from urban stormwater runoff in Daejeon city, Korea.
AB  - In this paper, stormwater runoff from an urban watershed with combined sewer
      systems located in Daejeon metropolitan city, Korea, was characterized to measure
      the stormwater runoff discharge rates and pollutant concentrations. The observed
      averaged event mean concentrations (EMCs) of combined sewer overflows (CSO) were
      536.1mg TSS/L, 467.7 mg TCODcr/L, 142.7 mg TBOD/L, 16.5mg TN/L, and 13.5mg TP/L.
      A detention basin was proposed to reduce CSO, and its essential design elements
      were discussed. The first flush significantly affected contaminant constituents
      in the descending order of suspended solid>organics>nutrients. Storage volumes
      for containing the first flush to improve water quality of the receiving stream
      can be estimated based on the total suspended solid loading. In this study,
      detention of the first flush equivalent to 5mm of precipitation could reduce CSO
      induced diffuse pollution loading to a receiving water body by up to 80% of the
      total suspended solid loading.

PMID- 16979285
TI  - Financing electronic waste recycling Californian households' willingness to pay
      advanced recycling fees.
AB  - The growth of electronic waste (e-waste) is of increasing concern because of its
      toxic content and low recycling rates. The e-waste recycling infrastructure needs
      to be developed, yet little is known about people's willingness to fund its
      expansion. This paper examines this issue based on a 2004 mail survey of
      California households. Using an ordered logit model, we find that age, income,
      beliefs about government and business roles, proximity to existing recycling
      facilities, community density, education, and environmental attitudes are
      significant factors for explaining people's willingness to pay an advanced
      recycling fee (ARF) for electronics. Most respondents are willing to support a 1%
      ARF. Our results suggest that policymakers should target middle-aged and older
      adults, improve programs in communities with existing recycling centers or in
      rural communities, and consider public-private partnerships for e-waste recycling
      programs.

PMID- 16979286
TI  - Prevalence and correlates for interstitial cystitis symptoms in women
      participating in a health screening project.
AB  - OBJECTIVES: To determine the prevalence of interstitial cystitis (IC) symptoms in
      an urban female population, to study their impact on quality of life and sexual
      function, and to identify correlates for IC symptoms. METHODS: Women attending a
      voluntary health survey project in Vienna underwent a detailed health
      investigation and completed a questionnaire containing the O'Leary-Sant IC
      questionnaire. Women with high (> or =12) symptom and problem scores including
      nocturia (>2) and pain were considered most likely to have IC. RESULTS: A total
      of 981 women, aged 19 to 89 yr (mean, 49.1+/-14.7 yr), participated in the study.
      Of these, 57.9% had a low IC symptom score (score 0-3), 25.9% mild IC symptoms
      (score 4-6), 13.9% moderate symptoms (score 7-11), and 2.3% a high symptom score
      (score 12-20). The IC problem score revealed a similar pattern. The overall
      prevalence of IC was 306/100,000 women with the highest value (464/100,000) in
      middle-aged women (40-59 yr). About two thirds of the women with moderate to high
      risk for IC reported an impairment of quality of life; 35% reported an effect on
      their sexual life. In a multivariate analysis, bowel disorders (p=0.016) and
      psychological stress (p=0.029) were correlated to the probability of IC.
      CONCLUSION: The prevalence of IC symptoms is higher than previously estimated and
      substantially affects quality of life and sexuality.

PMID- 16979287
TI  - The detrusor muscle: an innocent victim of bladder outlet obstruction.
AB  - OBJECTIVES: Benign prostatic hyperplasia (BPH) is considered a frequent cause of
      bladder outlet obstruction (BOO) and lower urinary tract symptoms (LUTS),
      although the physiopathologic mechanism through which BPH causes LUTS is not
      clear. Several morphologic and functional modifications of the bladder detrusor
      have been described in patients with BPH and could play a direct role in
      determining symptoms. The opinion is spreading that the enlarged prostates in
      patients with LUTS is nothing more than a mere bystander. Evidence has
      accumulated, however, supporting the role of BPH-related BOO as the direct cause
      determining bladder dysfunction and indirectly causing urinary symptoms. The
      present review addresses the bladder response to BOO, particularly focusing on
      the physiopathologic cascade that links obstructive BPH to bladder dysfunction.
      METHODS: A literature review of peer-reviewed articles has been performed,
      including both in vivo and in vitro studies on human tissue and animal model
      experiments. RESULTS: Epithelial and smooth muscle cells in the bladder wall are
      mechanosensitive, and in response to mechanical stretch stress caused by BOO,
      undergo modifications of gene expression and protein synthesis. This process
      involves several transduction mechanisms and finally alter the ultrastructure and
      physiology of cell membranes, cytoskeleton, contractile proteins, mitochondria,
      extracellular matrix, and neuronal networks. CONCLUSIONS: BOO is the initiator of
      a physiopathologic cascade leading to deep changing of bladder structure and
      function. Before being a direct cause of storing-phase urinary symptoms, the
      bladder is the first innocent victim of prostatic obstruction.

PMID- 16979288
TI  - The fate and management of high mercury-containing lamps from high technology
      industry.
AB  - This study investigated the fate and management of high mercury-contained lamps,
      such as cold cathode fluorescent lamps (CCFLs), ultraviolet lamps (UV lamps), and
      super high pressure mercury lamps (SHPs), from high technology industries in
      Taiwan, using material flow analysis (MFA) method. Several organizations, such as
      Taiwan Environmental Protection Administration, Taiwan External Trade Development
      Council, the light sources manufactories, mercury-containing lamps importer, high
      technology industrial user, and waste mercury-containing lamps treatment
      facilities were interviewed in this study. According to this survey, the total
      mercury contained in CCFLs, UV lamps, and SHPs produced in Taiwan or imported
      from other countries was 886kg in year 2004. Among the various lamps containing
      mercury, 57kg mercury was exported as primary CCFLs, 7kg mercury was wasted as
      defective CCFLs, and 820kg mercury was used in the high technology industries,
      including 463kg mercury contained in exported industrial products using CCFLs as
      components. On the contrary, only 59kg of mercury was exported, including 57kg in
      CCFLs and 2kg in UV lamps. It reveals that 364kg mercury was consumed in Taiwan
      during year 2004. In addition, 140kg of the 364kg mercury contained in lamps used
      by high technology industry was well treated through industrial waste treatment
      system. Among the waste mercury from high technology industry, 80kg (57%), 53kg
      (38%), and 7kg (5%) of mercury were through domestic treatment, offshore
      treatment, and emission in air, respectively. Unfortunately, 224kg waste mercury
      was not suitable treated, including 199kg mercury contained in CCFL, which is a
      component of monitor for personal computer and liquid crystal display television,
      and 25kg non-treated mercury. Thus, how to recover the mercury from the waste
      monitors is an important challenge of zero wastage policy in Taiwan.

PMID- 16979289
TI  - Determination of exposure and probable ingestion of fluoride through tea,
      toothpaste, tobacco and pan masala.
AB  - Levels of water soluble and acid soluble fluoride in tea, toothpaste, tobacco and
      pan masala (mouth freshener) were estimated. These items are, generally, ignored
      while calculating the total dietary intake of fluoride. Tea, toothpaste, tobacco,
      pan masala (with tobacco and without tobacco) frequently expose human body to
      3.88-137.09, 53.5-338.5, 28.0-113.0, 16.5-306.5 and 23.5-185.0 microg of fluoride
      per gram of these items, respectively. An effort was also made to quantify, on
      the basis of available studies, the probable human ingestion of fluoride through
      these substances. Increased leaching of fluoride from some of these substances
      has been observed in acidic conditions in the present study. The results can be
      extrapolated to acidic conditions of human stomach.

PMID- 16979290
TI  - Isolation and characterization of a mesophilic heavy-metals-tolerant sulfate
      reducing bacterium Desulfomicrobium sp. from an enrichment culture using
      phosphogypsum as a sulfate source.
AB  - A sulfate-reducing bacterium, was isolated from a 6 month trained enrichment
      culture in an anaerobic media containing phosphogypsum as a sulfate source, and,
      designated strain SA2. Cells of strain SA2 were rod-shaped, did not form spores
      and stained Gram-negative. Phylogenetic analysis of the 16S rRNA gene sequence of
      the isolate revealed that it was related to members of the genus Desulfomicrobium
      (average sequence similarity of 98%) with Desulfomicrobium baculatum being the
      most closely related (sequence similarity of 99%). Strain SA2 used thiosulfate,
      sulfate, sulfite and elemental sulfur as electron acceptors and produced sulfide.
      Strain SA2 reduced sulfate contained in 1-20g/L phosphogypsum to sulfide with
      reduction of sulfate contained in 2g/L phosphogypsum being the optimum
      concentration. Strain SA2 grew with metalloid, halogenated and non-metal ions
      present in phosphogypsum and with added high concentrations of heavy metals
      (125ppm Zn and 100ppm Ni, W, Li and Al). The relative order for the inhibitory
      metal concentrations, based on the IC(50) values, was Cu, Te>Cd>Fe, Co, Mn>F,
      Se>Ni, Al, Li>Zn.

PMID- 16979291
TI  - NMDA receptor mediated dendritic plasticity in cortical cultures after oxygen
      glucose deprivation.
AB  - Dendrites and spines undergo dynamic changes in physiological and pathological
      conditions. Dendritic outgrowth has been observed in surviving neurons months
      after ischemia, which is associated with the functional compensation. It remains
      unclear how dendrites in surviving neurons are altered shortly after ischemia,
      which might reveal the mechanisms underlying neuronal survival. Using primary
      cortical cultures, we monitored the dendritic changes in individual neurons after
      oxygen-glucose deprivation (OGD). Two to four hours of OGD induced approximately
      30-50% cell death in 24 h. However, the total dendritic length in surviving
      neurons was significantly increased after OGD with a peak at 6 h after re
      oxygenation. The increase of dendritic length after OGD was mainly due to the
      sprouting rather than the extension of the dendrites. The dendritic outgrowth
      after 2 h of OGD was greater than that after 4 h of OGD. Application of NMDA
      receptor blocker MK-801 abolished OGD-induced dendritic outgrowth, whereas
      application of AMPA receptor antagonist CNQX had no significant effects. These
      results demonstrate a NMDA receptor-dependent dendritic plasticity shortly after
      OGD, which provides insights into the early response of surviving neurons after
      ischemia.

PMID- 16979292
TI  - Repetitive transcranial magnetic stimulation for ALS. A preliminary controlled
      study.
AB  - Repetitive transcranial magnetic stimulation (rTMS) of brain can modulate
      cortical neurotransmission, a novel paradigm of repetitive stimulation termed
      continuous theta-burst stimulation (cTBS) produces a pronounced and prolonged
      suppression of motor cortex excitability. The aim of this preliminary study was
      to investigate whether cTBS of motor cortex could have any beneficial effect in
      patients with amyotrophic lateral sclerosis (ALS). We performed a double-blind,
      placebo-controlled trial. Twenty patients with definite ALS were randomly
      allocated to blinded active or placebo stimulation. Repetitive stimulation of the
      motor cortex was performed for five consecutive days every month for six
      consecutive months. The primary outcome was the rate of decline as evaluated with
      the ALS functional rating scale. The treatment was well tolerated by the
      patients. Fifteen patients (seven active and eight sham) completed the study and
      were included in the 6-months analysis. Both active and sham patients
      deteriorated during treatment, however, active patients showed a modest but
      significant slowing of the deterioration rate. Though we cannot be sure whether
      the effects observed can be attributed to cTBS, because of the restricted number
      of patients studied, further investigation on a larger group of ALS patients is
      warranted. The results of the pilot study might open up a new therapeutic
      perspective in ALS based on neuromodulation.

PMID- 16979293
TI  - Neuropeptide Y mediates ghrelin-induced feeding in the goldfish, Carassius
      auratus.
AB  - Intracerebroventricular (ICV) and intraperitoneal (IP) administration of n
      octanoic acid-modified ghrelin stimulates food intake in the goldfish. We
      examined the involvement of neuropeptide Y (NPY) in the orexigenic action of
      ghrelin using a NPY Y1-receptor antagonist, BIBP-3226. Food intake induced by ICV
      or IP injection of ghrelin was suppressed by ICV preinjection of BIBP-3226 for 1
      h. We then examined whether ghrelin affects the expression of NPY mRNA in the
      goldfish brain using a real-time PCR method. ICV, but not IP, administration of
      ghrelin at a dose sufficient to stimulate food intake increased the expression of
      brain NPY mRNA obtained from 2 h after treatment. These results indicate that the
      orexigenic action of central ghrelin is mediated by the release of NPY in the
      brain with stimulating NPY synthesis, and that peripheral ghrelin also stimulates
      food intake via brain NPY pathway.

PMID- 16979294
TI  - Comparing nucleus accumbens and dorsal striatal dopamine responses to self
      administered cocaine in naive rats.
AB  - Dopamine (DA) responses in the nucleus accumbens (NAcc) and dorsal striatum (DS)
      are commonly associated with different aspects of cocaine effects. Enhanced NAcc
      DA has been most convincingly linked with the positive reinforcing effects of
      cocaine, while DS DA is thought to mediate cocaine-induced motoric effects.
      Though several studies have shown NAcc DA enhancement following cocaine self
      administration, very little work has examined the effects of cocaine self
      administration on DS DA. In this study, DA levels in the NAcc and DS, and
      locomotor responses to a single self-administered cocaine injection (1.5mg/kg)
      were assessed in operant-trained, drug-naive Sprague-Dawley rats. Locomotor
      activity, NAcc and DS DA levels increased significantly over baseline activity
      immediately after cocaine injection. However, while basal and cocaine-stimulated
      NAcc DA concentrations (nM) were significantly greater than DS DA levels, the
      magnitude of response was statistically comparable between brain regions. These
      findings indicate that, though both the NAcc and DS are importantly involved in
      the dopaminergic response to self-administered cocaine in drug-naive rats, basal
      DA differences in dialysis data are obscured by statistical conversions to
      baseline percentages.

PMID- 16979295
TI  - Toxicity and behavioral effects of dimethylsulfoxide in planaria.
AB  - In this work, we describe aspects of the toxicity and behavioral effects of
      dimethylsulfoxide (DMSO) in planaria. Planarian worms have traditionally been a
      favored animal model in developmental biology. More recently, this organism is
      being recognized as an animal model in neuropharmacology research. DMSO is often
      used in cell and tissue culture as a cryoprotectant agent and is also commonly
      used to enhance the solubility of hydrophobic drugs in aqueous solutions. This
      compound can elicit various physiological effects in both vertebrates and
      invertebrates. Many drugs and drug candidates are hydrophobic, needing solvents
      like DMSO to be able to reach their physiological targets. As planaria becomes
      increasingly popular in neuropharmacology research, a description of the DMSO
      effects in this organism is essential. We found that DMSO is toxic to planarians
      at concentrations above 5% (705 mM), with an LD(50) of 10% (1.4M) at exposure
      times above 5 min. At sub-toxic concentrations, DMSO decreases planarian
      exploratory behavior in a concentration-dependent manner. This reduction in
      locomotor behavior is reversible and preincubation-independent. DMSO at a
      concentration of 0.1% (14.1 mM), which is usually enough to solubilize
      hydrophobic substances in aqueous solutions, did not display any toxic or
      behavioral effects in planaria. Therefore, in this animal model, DMSO
      concentrations above 0.1% should be avoided in order to be able to reliably
      observe any behavioral or toxic effects of hydrophobic drugs.

PMID- 16979296
TI  - Purification and properties of NrtC and NrtD, the ATP-binding subunits of the ABC
      nitrate/nitrite transporter of Phormidium laminosum.
AB  - A genomic region from the thermophilic, filamentous, nondiazotrophic
      cyanobacterium Phormidium laminosum including nrtC and nrtD was cloned and
      sequenced. These genes encode NrtC and NrtD, the ATP-binding subunits of the ABC
      bispecific transporter of nitrate/nitrite NRT. We report a different nrtC
      sequence from the one previously reported (Merchan et al., Plant Mol. Biol.
      28:759-766, 1995) and we identified the presence of nrtD gene downstream nrtC in
      the nirA operon. Each gene was expressed in E. coli cells as a hexahistidine
      tagged fusion protein. The recombinant proteins (His(6)NrtC and His(6)NrtD) were
      purified, and their ability to catalyze the hydrolysis of ATP and other
      nucleosides triphosphate was characterized. Both subunits showed its maximum
      ATPase activity at 45-50 degrees C and pH 8.0, and similar K(m) (0.49 and 0.43
      mM) and V(max) (0.085 and 0.114 U mg(-1) protein, respectively) values were
      calculated. The native NrtC subunit purified from nitrogen-starved cells of P.
      laminosum also hydrolyzed ATP in vitro in the absence of other components of NRT.
      These findings indicated that NrtC and NrtD are responsible for ATP-hydrolysis to
      energize the active transporter NRT. The effect of some activators (Mg(2+)) and
      inhibitors (ADP) on the ATPase activity of the subunits was assessed as well as
      the effect of some potential regulatory metabolites on His(6)NrtC. The existence
      in vitro of homodimers of either NrtC or NrtD but not heterodimers of both
      subunits was confirmed by matrix assisted laser desorption ionization-time of
      flight mass spectrometry and/or electrophoresis in non-denaturing conditions.
      Finally, the existence in vivo of NrtC-NrtD heterodimers is discussed.

PMID- 16979297
TI  - Commentary: concomitant chemotherapy and radiation for limited stage small cell
      lung cancer and benefit of adding additional drug into chemotherapy regimen for
      advanced non-small cell lung cancer.

PMID- 16979298
TI  - Alzheimer's disease and Helicobacter pylori infection: Defective immune
      regulation and apoptosis as proposed common links.
AB  - Although degenerative diseases of the central nervous system, including
      Alzheimer's disease (AD), have an increasingly high impact on aged population
      their association with Helicobacter pylori (H. pylori) infection has not as yet
      been thoroughly researched. Current H. pylori infection appears to induce
      irregular humoral and cellular immune responses that, owing to the sharing of
      homologous epitopes (molecular mimicry), cross-react with components of nerves,
      thereby contributing and possibly perpetuating the apoptotic neural tissue damage
      observed in neurodegenerative diseases including AD. An association between AD
      and H. pylori infection has been recently addressed by two studies. A higher
      seropositivity for anti-H. pylori immunoglobulin G antibodies in 30 patients with
      AD than in 30 age-matched controls was reported in one study; this serological
      test, however, has limitations because it does not discriminate between current
      and old infections. In the other study, by introducing the histological method
      (the actual gold standard) for diagnosis of H. pylori infection, we reported a
      higher prevalence of H. pylori infection in 50 AD patients than in 30 anemic
      controls. This pathogen may influence the pathophysiology of AD by promoting
      platelet and platelet-leukocyte aggregation; releasing various pro-inflammatory
      and vasoactive substances; developing cross-mimicry with host antigens; producing
      reactive oxygen metabolites and circulating lipid peroxides; influencing the
      apoptotic process; and increasing, through induction of atrophic gastritis,
      homocysteine, which contributes to vascular disorders implicated in endothelial
      damage and neurodegeneration.

PMID- 16979299
TI  - Asymmetric somatic stem cells division plays a critical role in cell senescence.

PMID- 16979300
TI  - Pathophysiology of postoperative delirium: systemic inflammation as a response to
      surgical trauma causes diffuse microcirculatory impairment.
AB  - Postoperative delirium represents a serious complication after major surgery.
      Patients suffer from anxiety, hallucinations and delusions, and have higher
      postoperative morbidity and mortality. Generally, the role of acetylcholine
      deficiency in delirium pathophysiology is widely accepted. How this pathologic
      state evolves in the postoperative period is the topic of this paper. Systemic
      inflammation as a response to surgical trauma causes diffuse microcirculatory
      impairment. The most relevant pathologies include leukocyte adhesion to vessel
      lining, endothelial cell swelling, perivascular oedema, narrowing of capillar
      diameters, and lowered functional capillary density. These morphological changes
      lead to a decrease of nutritive perfusion and to longer diffusion distance for
      oxygen. Because acetylcholine synthesis is especially sensitive to low oxygen
      tension, symptoms of its deficiency readily develop. Therapeutic tools to
      modulate excessive inflammation are available, therefore new strategies of
      delirium treatment should be implemented in clinical praxis, as well as in
      preventive measures.

PMID- 16979301
TI  - Ascites is the primary cause of cancer antigen-125 (CA-125) elevation in systemic
      lupus erythematosus (SLE) patients with nephrotic syndrome.
AB  - Tumor markers or tumor antigens are used for the monitoring of the response to
      treatment, follow-up, and potentially for diagnosis and screening. However, use
      of CA-125 serum assay as a single diagnostic tool is restricted by the fact that
      it is also produced by normal epithelia, not only by the ovarian cancer cells.
      Systemic lupus eryhtematosus (SLE) and related systemic autoimmune syndromes are
      associated with elevation of CA-125. In this group of patients antigen elevation
      had been tried to be linked with SLE disease activity. Although not found to be
      related with the disease activity, CA-125 serum levels were found to be related
      with the presence of nephrotic syndrome in the English literature. Although
      particularly important, the presence of ascites was not taken into consideration
      during the statistical analysis of the relationship between CA-125 elevation and
      nephrotic syndrome in SLE patients. However most of the SLE patients with
      nephrotic syndrome would have had accompanying ascites secondary to protein loss.
      Ascites itself could induce elevation in CA-125 serum levels. With this in mind
      we can hypothesize that the development of ascites was the primary cause for the
      elevation of CA-125 in SLE patients with nephrotic syndrome rather than the
      nephrotic syndrome itself. Probably the presence of ascites was the cause of
      observed relationship. Most likely ascites was a confounding variable biasing the
      results and statistical analysis. Failure to control for the presence of
      confounding variables such as ascites might lead to bias in all clinical trials.
      Otherwise a causative role for nephrotic syndrome in the elevation of serum CA
      125 level seems somewhat inconsequential.

PMID- 16979303
TI  - Comparative study of the expression of cellular cycle proteins in cervical
      intraepithelial lesions.
AB  - Interaction of human papilloma virus oncoproteins E6 and E7 with cell cycle
      proteins leads to disturbances of the cell cycle mechanism and subsequent
      alteration in the expression of some proteins, such as p16INK4a, cyclin D1, p53
      and KI67. In this study, we compared alterations in the expression of these
      proteins during several stages of intraepithelial cervical carcinogenesis.
      Accordingly, an immunohistochemical study was performed on 50 cervical biopsies,
      including negative cases and intraepithelial neoplasias. The expression patterns
      of these markers were correlated with the histopathological diagnosis and
      infection with HPV. The p16INK4a, followed by Ki67, showed better correlation
      with cancer progression than p53 and cyclin D1, which recommends their use in the
      evaluation of cervical carcinogenesis. These monoclonal antibodies can be applied
      to cervical biopsy specimens to identify lesions transformed by oncogenic HPV,
      separating CIN 1 (p16INK4a positive) and identifying high-grade lesions by an
      increase in the cellular proliferation index (Ki67). In this way, we propose
      immunomarkers that can be applied in clinical practice to separate patients who
      need a conservative therapeutic approach from those who require a more aggressive
      treatment.

PMID- 16979302
TI  - Postmortem findings and opportunistic infections in HIV-positive patients from a
      public hospital in Peru.
AB  - There is a paucity of HIV autopsy data from South America and none that document
      the postmortem findings in patients with HIV/AIDS in Peru. The purpose of this
      autopsy study was to determine the spectrum of opportunistic infections and the
      causes of mortality in HIV-positive patients at a public hospital in Lima.
      Clinico-epidemiological information regarding HIV infection in Peru is also
      reviewed. Sixteen HIV-related hospital postmortems, performed between 1999 and
      2004, were included in this retrospective analysis. The primary cause of death
      was established in 12 patients: one died of neoplasia and 11 of infectious
      diseases, including 3 from pulmonary infection, 7 from disseminated infection,
      and 2 from central nervous system infection (one case had dual pathology).
      Opportunistic infections were identified in 14 cases, comprising cytomegalovirus,
      histoplasmosis, cryptococcosis, toxoplasmosis, Pneumocystis pneumonia,
      aspergillosis, tuberculosis, varicella zoster virus, and cryptosporidiosis.
      Fourteen patients had at least one AIDS-related disease that had been neither
      clinically suspected nor diagnosed premortem. Moreover, 82% of the diagnoses
      considered to be of important clinical significance had not been suspected
      antemortem. The spectrum and frequency of certain opportunistic infections
      differed from other South American autopsy studies, highlighting the importance
      of performing HIV/AIDS postmortems in resource-limited countries where locally
      specific disease patterns may be observed.

PMID- 16979304
TI  - Intention to utilize formal help in a sample with alcohol problems: a prospective
      study.
AB  - BACKGROUND: Studies investigating factors of treatment entry have predominantly
      focussed on persons that have already taken an initial step in the process of
      help-seeking. With particular emphasis on intention to utilize help, this study
      aims to detect predictors for alcohol-related help-seeking among a non-help
      utilizing sample. METHODS: Using 312 individuals with diverse alcohol problems
      (dependence, abuse, at-risk drinking), intention to utilize help was assessed in
      addition to evidence based predictors for utilization of help (e.g. severity of
      alcohol problem, prior help-seeking). RESULTS: In addition to prior utilization
      of help (OR=9.76, CI: 4.60-20.74) and adverse consequences from drinking
      (OR=1.13, CI: 1.02-1.25), intention to utilize help (OR=4.84, CI: 2.04-11.51) was
      a central predictor for help-seeking. Among individuals who had not obtained
      prior help, individuals intending to seek help were 8.7 times more likely to
      utilize help than those not intending to seek help (CI: 1.05-72.2). CONCLUSIONS:
      In the past, intention to utilize help has been neglected from models
      investigating treatment entry. This study's findings show that intention is a
      central factor for utilization of alcohol-specific formal help. Consequently,
      brief interventions focusing on enhancing motivation are expected to improve
      early help-seeking among general hospital patients with diverse alcohol problems.

PMID- 16979305
TI  - Theoretical foundation to estimate the relative efficiencies of the Jukes
      Cantor+gamma model and the Jukes-Cantor model in obtaining the correct
      phylogenetic tree.
AB  - This paper deals with the theoretical foundation to estimate the relative
      efficiency (probability of inferring the true tree) of different nucleotide
      substitution models. A novel theoretical approach has been developed to estimate
      the relative efficiency of nucleotide substitution models based on the neighbor
      relation method. The theory was developed directly by using the four-point
      condition. Initially theoretical formulas for the Jukes-Cantor+gamma (JC+Gamma)
      model and the Jukes-Cantor (JC) model were developed to estimate their relative
      efficiencies. Theoretical formulas were used on several model topologies for both
      models to obtain a true tree. Extensive simulations were performed on the same
      set of trees to test the strength of the theoretical approach. Simulation results
      demonstrated a good agreement with results obtained by the theoretical
      estimation. Overall the theoretical foundation for estimating model efficiencies
      is very accurate.

PMID- 16979306
TI  - Performance evaluation of a competitive ELISA test used for bluetongue antibody
      detection in France, a recently infected area.
AB  - In 1998, bluetongue (BT) was introduced in northern Africa and then extended to
      northern latitudes including the French island of Corsica. Following the
      outbreaks in Corsica in 2000 and 2001, cross-sectional studies and surveillances
      have been set up in Corsica and also in the southern part of mainland France, a
      disease-free area but considered at high risk because of its proximity. The
      surveillance was based on regular blood sampling of susceptible species and
      antibody detection by a commercial competitive ELISA kit (cELISA). The
      performance of this cELISA was evaluated on both field results obtained during
      the 2001 surveillance campaigns and experimental results. ROC analyses were
      carried out using RT-PCR results as gold standard for determining the infection
      status of animals. From all these sets of data, cut-off values optimising the
      diagnostic accuracy of the test were computed. Their values ranged around the
      manufacturer's 50% threshold from 41% to 63%. The area under the ROC curve
      obtained from field data was 0.843 (95% CI: 0.762-0.923). In all our results, it
      appeared also that the specificity of the cELISA test was always perfect if the
      cut-off was at least at 80%. This cELISA test does not seem sufficient to
      diagnose BT disease in animals with BT-like symptoms. However, complementary data
      are needed to better estimate sensitivity and specificity values of this BT test
      for its use either as a diagnostic tool in infected areas or as a screening test
      in BT-free areas. The use and validity of RT-PCR results as gold standard are
      discussed. As the lack of suitable data strongly limited the applicable analyses,
      a discussion based on the OIE recommendations about test evaluation is initiated.

PMID- 16979307
TI  - Limited BVDV transmission and full protection against CSFV transmission in pigs
      experimentally infected with BVDV type 1b.
AB  - Bovine viral diarrhea virus (BVDV) in pigs may interfere with the detection and
      epidemiology of classical swine fever virus (CSFV). To investigate the importance
      of BVDV infections in pigs, first we studied the transmission dynamics of a
      recent BVDV field isolate. Subsequently, the protection of BVD antibodies against
      transmission and clinical disease of CSF virus was studied. Only limited
      transmission of BVDV occurred (R = 0.20), while no CSFV transmission occurred in
      pigs with BVDV antibodies. We concluded that BVDV transmission among pigs is
      possible, but seems to be limited and thus the virus should disappear from a
      population if no new introductions occur. Furthermore, the presence of BVD
      antibodies may completely prevent the transmission of CSFV and therefore could
      protect pigs against classical swine fever. It was also noticed that double
      infections with BVDV and CSFV were incorrectly diagnosed using the neutralization
      peroxidase linked assay (NPLA), which is the golden standard for antibody
      detection. This might hamper the diagnosis of CSF in herds with a high BVD
      prevalence.

PMID- 16979308
TI  - Flock-prevalence of border disease virus infection in Basque dairy-sheep
      estimated by bulk-tank milk analysis.
AB  - Bulk-tank milk (BTM) samples from 154 sheep flocks were used to estimate BDV
      prevalence in the Basque Country in Spain using an ELISA and a RT-PCR test. The
      proportion of antibody-positive flocks was 68% but varied significantly between
      provinces and was 93% in Araba and 54-55% in Bizkaia and Gipuzkoa. Most ELISA
      positive flocks had very low antibody inhibition percentage (AIP) indicating high
      seroprevalence and recent BDV exposure. However, only 9% flocks were PCR-positive
      suggesting few infected ewes were being milked at the time of sampling.
      Phylogenetic analysis of the 5' NCR sequences of BDV from seven infected flocks
      showed that all except one clustered within the group formed by BDV type C
      strains from a previous study in the region, whereas the remaining isolate was
      closest to BDV type A. These results suggest that BDV strains in most Basque
      flocks have a common origin and differences in prevalence between provinces are
      associated to recent events affecting BDV spread such as use of communal pastures
      and sheep trading. The widespread distribution of BDV in the region, advocates
      for the implementation of BDV control strategies and highlights the potential
      risk of sheep as a pestivirus reservoir for other species.

PMID- 16979309
TI  - Acute perfusion of BMAA in the rat's striatum by in vivo microdialysis.
AB  - The present study is concerned with the hypothetical toxicity of beta-N
      methylamino-L-alanine (BMAA), a compound that has been hypothesized to produce
      amyotrophic lateral sclerosis/Parkinson-dementia complex. We have used the
      microdialysis technique to perfused different concentrations of BMAA in the rat's
      striatum 24h after the implantation of a microdialysis probe (day 1). BMAA
      perfusion produced a dose-response increase in the extracellular output of
      dopamine. Forty-eight hours after implantation of the probe (day 2), we have
      perfused MPP+ 1 mM to check the integrity of the dopaminergic terminals present
      around the cannula. Only the highest concentration of BMAA studied, 50mM,
      produced a clear decrease in the extracellular output of dopamine after MPP+
      perfusion. However, this decrease was very similar, even smaller, to that
      obtained in a previous study carried out by us with MPP+ 1 mM, a dose much lower
      than that used for BMAA. Our model to study toxicity in the striatal dopaminergic
      terminal did not show that acute perfusion of BMAA at high doses produces a clear
      damage to the dopaminergic terminals.

PMID- 16979311
TI  - Feasibility and acceptability of restorative yoga for treatment of hot flushes: a
      pilot trial.
AB  - OBJECTIVE: To determine the feasibility and acceptability of a restorative yoga
      intervention for the treatment of hot flushes in postmenopausal women. METHODS: A
      pilot trial in 14 postmenopausal women experiencing > or =4 moderate to severe
      hot flushes per day or > or =30 moderate to severe hot flushes per week. The
      intervention consisted of eight restorative yoga poses taught in a 3-h
      introductory session and 8 weekly 90-min sessions. Feasibility was measured by
      recruitment rates, subject retention and adherence. Acceptability was assessed by
      subject interview and questionnaires. Efficacy measures included change in
      frequency and severity of hot flushes as recorded on a 7-day diary. RESULTS:
      Recruitment was accomplished as planned. The majority of study subjects (93%)
      completed the trial. Of those who completed the trial, 92% attended seven or more
      of the eight yoga sessions. The majority of the subjects were satisfied with the
      study and 75% continued to practice yoga 3 months after the study. Mean number of
      hot flushes per week decreased by 30.8% (95% CI 15.6-45.9%) and mean hot flush
      score decreased 34.2% (95% CI 16.0-52.5%) from baseline to week 8. No adverse
      events were observed. CONCLUSIONS: This pilot trial demonstrates that it is
      feasible to teach restorative yoga to middle-aged women without prior yoga
      experience. The high rates of subject retention and satisfaction suggest that
      yoga is an acceptable intervention in this population. Our results indicate that
      a larger, randomized controlled trial to explore the efficacy of restorative yoga
      for treatment of menopausal symptoms would be safe and feasible.

PMID- 16979310
TI  - The effect of the supply of rumen degradable protein and metabolisable protein on
      negative energy balance and fertility in dairy cows.
AB  - Reproduction in dairy cattle is negatively affected by a negative energy balance
      (NEB), a combination of the deposition or mobilisation of fat and protein. The
      mode of action of NEB on fertility is not always clear, but the severity, length,
      and probably also the nature of the NEB may be involved. Extensive mobilisation
      of fat is expected to have detrimental effects on liver function due to the
      accumulation of non-esterified long chain fatty acids, impairing the
      detoxification of ammonia into urea. Protein evaluation systems nowadays use the
      concept of metabolisable protein (MP) and distinguish between rumen degradable
      protein (RDP) and rumen undegradable protein (RUP). Mobilisation of protein
      itself does not seem to have negative effects on reproduction. However, when
      protein is extensively degraded in the rumen or used as an energy source,
      metabolic residues like ammonia and urea will result. Such residues may exert
      metabolic effects that are often detrimental to reproduction and fertility.
      Ammonia is believed to play a role starting before ovulation, whereas urea mainly
      interferes negatively after fertilisation. But, urea is also believed to
      aggravate the severity of NEB and its effect on fertility by preventing or
      delaying the start of cyclicity. Besides, urea has been shown to lower the pH in
      the uterine fluid, giving rise to disturbances in follicular development and
      embryonic growth. It is recommended to limit the level of rumen degradable
      protein in the diet to 10% in the DM.

PMID- 16979312
TI  - Nitric oxide inhibitory substances from the rhizomes of Dioscorea membranacea.
AB  - Thai medicinal plants locally known as Hua-Khao-Yen were examined for their
      inhibitory activities against lipopolysaccharide (LPS) induced nitric oxide (NO)
      production in RAW 264.7 cell lines. Among the plant species studied, an ethanolic
      extract of Dioscorea membranacea exhibited the most potent inhibitory activity,
      with an IC(50) value of 23.6 microg/ml. From this extract, eight compounds [two
      naphthofuranoxepins (1, 2), one phenanthraquinone (3), three steroids (4-6) and
      two steroidal saponins (7, 8)] were isolated and further investigated for their
      inhibitory properties of NO production. It was found that diosgenin-3-O-alpha-L
      rhamnosyl (1-->2)-beta-D-glucopyranoside (7) possessed the highest activity
      (IC(50)=3.5 microM), followed by dioscoreanone (3, IC(50)=9.8 microM) and
      dioscorealide B (2, IC(50)=24.9 microM). Regarding structural requirements of
      diosgenin derivatives for NO production inhibitory activity, compound 7 which has
      a rhamnoglucosyl moiety at C-3 exhibited much higher activity than compounds that
      have either a diglucosyl substitution (8) or its aglycone (9); whereas, hydroxyl
      substitution at position 8 of naphthofuranoxepin derivatives conferred higher
      activity than the methoxyl group. It is concluded that diosgenin-3-O-alpha-L
      rhamnosyl (1-->2)-beta-D-glucopyranoside (7), dioscoreanone (3) and dioscorealide
      B (2) are active principles for NO inhibitory activity of Dioscorea membranacea.
      Compounds 1-3 were also tested for the inhibitory effect on LPS-induced TNF-alpha
      release in RAW 264.7 cells. The result revealed that 3 possessed potent activity
      against TNF-alpha release with an IC(50) value of 17.6 microM, whereas, 1 and 2
      exhibited mild activity. The present study may support the use of Dioscorea
      membranacea by Thai traditional doctors for treatment of the inflammatory
      diseases.

PMID- 16979313
TI  - Influence of purified saponin mixture from Astragalus corniculatus Bieb. on
      phagocytic cells in Graffi-tumor bearing hamsters.
AB  - A purified saponin mixture (PSM) from Astragalus corniculatus Bieb. protected
      significantly hamsters against the experimental Graffi myeloid tumor. The
      application of PSM increased the survival rates, prolonged mean survival time and
      the tumor growth was markedly reduced. A purified saponin mixture (PSM) of
      Astragalus corniculatus Bieb. was evaluated for its immunostimulating potentials
      on the phagocytic cells in Graffi-tumor bearing hamsters. The number, migration
      and phagocytic indexes of peritoneal macrophages (pMos) and of blood
      polymorphonuclear leukocytes (PMNs) were evaluated in healthy and Graffi-tumor
      bearing hamsters (G-TBH) treated with PSM. It was established that the Graffi
      myeloid tumor induced suppression of the phagocytic abilities of pMos and PMNs.
      The number and migration of pMos was significantly decreased during the whole
      period of observation. All tested parameters-number, migration and phagocytic
      activities of pMos, as well as phagocytic ability of PMNs increased significantly
      in healthy and G-TBH after i.p. application of the 50 mg/kg body weight PSM. The
      PMS extracts from Astragalus corniculatus Bieb. are isolated and examined and
      their immunostimulating and immunorestorating impact on phagocitic cells was
      proven for the first time. This effect could be due to their high content of
      purified saponins.

PMID- 16979314
TI  - Functional imaging in CT.
AB  - Fast data acquisition imaging technologies such as modern computed tomography
      (CT) allow contrast agents to be used as tracers and nuclear medicine methodology
      may be used to derive a variety of functional/physiological information from
      dynamic CT. This article describes the theoretical basis and some practical
      applications of this idea including the measurement of perfusion, capillary
      permeability, vascular volumes, renal function and tumour responses to therapy.

PMID- 16979315
TI  - Physiological aspects. Part 1 in a series of papers devoted to surfactants in
      microbiology and biotechnology.
AB  - Surfactants, both chemical and biological, are amphiphilic compounds which can
      reduce surface and interfacial tensions by accumulating at the interface of
      immiscible fluids and increase the solubility, mobility, bioavailability and
      subsequent biodegradation of hydrophobic or insoluble organic compounds.
      Investigations on their impacts on microbial activity have generally been limited
      in scope to the most common and best characterized surfactants. Recently a number
      of new biosurfactants have been described and accelerated advances in molecular
      and cellular biology are expected to expand our insights into the diversity of
      structures and applications of biosurfactants. Biosurfactants play an essential
      natural role in the swarming motility of microorganisms and participate in
      cellular physiological processes of signaling and differentiation as well as in
      biofilm formation. Biosurfactants also exhibit natural physiological roles in
      increasing bioavailability of hydrophobic molecules and can complex with heavy
      metals, and some also possess antimicrobial activity. Chemical- and indeed bio
      surfactants may also be added exogenously to microbial systems to influence
      behaviour and/or activity, mimicking the latter effects of biosurfactants. They
      have been exploited in this way, for example as antimicrobial agents in disease
      control and to improve degradation of chemical contaminants. Chemical surfactants
      can interact with microbial proteins and can be manipulated to modify enzyme
      conformation in a manner that alters enzyme activity, stability and/or
      specificity. Both chemical- and bio-surfactants are potentially toxic to specific
      microbes and may be exploited as antimicrobial agents against plant, animal and
      human microbial pathogens. Because of the widespread use of chemical surfactants,
      their potential impacts on microbial communities in the environment are receiving
      considerable attention.

PMID- 16979316
TI  - Impact of isolated tumor cells in sentinel lymph nodes detected by
      immunohistochemical staining.
AB  - AIM: Isolated tumor cells (ITCs) in lymph nodes are defined histologically as
      node-negative. The clinical impact of ITCs in sentinel lymph nodes (SLNs) remains
      unclear. We report the prognosis of breast cancer patients with ITC-positive SLNs
      detected by immunohistochemical staining. PATIENTS AND METHODS: One hundred and
      sixty-five breast cancer patients with histologically negative SLNs were seen
      between January 1998 and December 2000. In 69 patients, sentinel node biopsy
      (SNB) was immediately followed by axillary lymph node dissection, and 96 had
      undergone SNB alone. Permanent sections of 301 SLNs were re-examined after
      hematoxylin-eosin staining and cytokeratin 19 immunohistochemical staining.
      RESULTS: ITCs were found in 18 SLNs of 17 patients and a micrometastasis was
      found in one SLN of one patient. As of November 2005, only one patient with ITCs
      in one SLN had supraclavicular lymph node recurrence. In contrast, 18 of the 147
      patients with negative SLNs had tumor recurrence. Surgical management of the
      axilla had no influence on recurrence-free survival in all of the patients.
      CONCLUSION: This study shows that breast cancer patients with ITC-positive SLNs
      should be clinically managed as node-negative patients.

PMID- 16979317
TI  - Enhanced cued recall has a high utility as a screening test in the diagnosis of
      Alzheimer's disease and mild cognitive impairment in Turkish people.
AB  - Enhanced cued recall (ECR) is highly sensitive and specific in discrimination of
      demented from non-demented elderly persons. The nature of the test promises that
      it can be applicable to subjects in different cultures and education level. We
      studied the utility of the test in a Turkish population. Eighty consecutive cases
      with dementia or mild cognitive impairment (MCI) and 33 elderly controls were
      studied. The utility of ECR was high in discriminating dementia from controls
      (area under curve (AUC)) of the ROC curve: 0.907 (95% confidence interval (CI):
      0.830-0.953 for total recall), Alzheimer's disease from controls (AUC: 0.990
      (95%CI: 0.934-0.998 for total recall)) and moderate (AUC: 0.625 (95%CI: 0.545
      0.812 for third free recall)) in discriminating MCI from controls. Education did
      not affect the utility of the test. We conclude that ECR is a valuable test in
      assessment of elderly Turkish patients with a complaint of memory impairment.

PMID- 16979318
TI  - A 6-month follow-up of the effects of an information and communication technology
      (ICT) training programme on people with intellectual disabilities.
AB  - We investigated the long-term effects of an information and communication
      technology (ICT) training programme for people with intellectual disabilities
      (ID). A community-based ICT training programme was designed to enhance the
      computer skills of people with ID and prepare them to make use of ICT in their
      daily life. Of the 100 who had participated in the original ICT training
      programme, 59 of them and their caregivers agreed to participate in the follow-up
      interview. A computer skills checklist was used to assess the ICT competence of
      the participants before training, after training, and at the 6-month follow-up
      assessment. All caregivers were interviewed at the 6-month follow-up session to
      explore the use of ICT by people with ID and their needs for further training.
      Results from repeated measures ANOVA showed that participants maintained at the 6
      month follow-up the basic ICT skills that they acquired during training [F=13.86,
      p<0.001]. Caregivers reported that participants spent more time in using the
      computers, but still needed occasional guidance. They also reported a need to
      advance their ICT skills beyond the basic computer training. We concluded that
      ICT training for people with ID would help them in maximizing the benefits of
      information technology via computers.

PMID- 16979319
TI  - Building bridges between neural models and complex decision making behaviour.
AB  - Diffusion processes, and their discrete time counterparts, random walk models,
      have demonstrated an ability to account for a wide range of findings from
      behavioural decision making for which the purely algebraic and deterministic
      models often used in economics and psychology cannot account. Recent studies that
      record neural activations in non-human primates during perceptual decision making
      tasks have revealed that neural firing rates closely mimic the accumulation of
      preference theorized by behaviourally-derived diffusion models of decision
      making. This article bridges the expanse between the neurophysiological and
      behavioural decision making literatures specifically, decision field theory
      [Busemeyer, J. R. & Townsend, J. T. (1993). Decision field theory: A dynamic
      cognitive approach to decision making in an uncertain environment. Psychological
      Review, 100, 432-459], a dynamic and stochastic random walk theory of decision
      making, is presented as a model positioned between lower-level neural activation
      patterns and more complex notions of decision making found in psychology and
      economics. Potential neural correlates of this model are proposed, and relevant
      competing models are also addressed.

PMID- 16979321
TI  - Influence of physiological and subjective arousal on food intake in humans.
AB  - OBJECTIVES: This study explored the influence of physiologic and subjective
      arousal on ambient factors of the food environment, such as the eating location,
      the presence of other people, sound, and time of day and on food intake. It was
      hypothesized that the influence of environmental stimuli on food intake would be
      mediated by arousal. METHODS: College students were asked to wear heart rate
      monitors and to record their food intake in a 7-d diet diary. Subjective arousal
      (elation and excitement) and aspects of the eating environment were recorded for
      each meal occasion. RESULTS: Results showed that subjective arousal seems to be
      related to food intake (P < 0.01) and appears to be affected by environmental
      stimuli such as the eating location (P < 0.01) and the number of people present
      (P < 0.01), but only small effects of some environmental stimuli on heart rate
      were found with higher average heart rates in restaurants (P < 0.05). No effects
      of heart rate on food intake were detected. Regression analyses failed to show
      arousal as a significant mediator between environmental stimuli and food intake.
      CONCLUSION: It can be concluded that, for normal individuals in their everyday
      environment, ambient influences on food intake are not mediated by changes in
      arousal. However, the environment and the emotional state of the individual
      appear to play a role in the individual's eating behavior.

PMID- 16979322
TI  - Effect of proteins from beef, pork, and turkey meat on plasma and liver lipids of
      rats compared with casein and soy protein.
AB  - OBJECTIVE: We assessed the effect of dietary proteins isolated from beef, pork,
      and turkey meat on concentrations of cholesterol and triacylglycerols in plasma,
      lipoproteins, and liver and the composition of the microsomal membrane (fatty
      acids, phosphatidylcholine/phosphatidylethanolamine ratio) compared with that of
      casein and soy protein in rats. METHODS: Five groups of 12 rats each were fed
      semisynthetic diets for 20 d that contained 200 g/kg of proteins isolated from
      beef, pork, or turkey meat or, as controls, casein or soy protein. RESULTS: Rats
      fed beef, pork, or turkey proteins did not differ in cholesterol concentrations
      of plasma, lipoproteins, and liver and in composition of microsomal membrane from
      rats fed the casein diet. All groups fed a protein from an animal source had
      higher very low-density lipoprotein (VLDL) and liver cholesterol concentrations
      than did rats fed soy protein. However, rats fed pork protein had lower
      concentrations of triacylglycerols in liver, plasma, and VLDL and lower mRNA
      concentrations of sterol regulatory element binding protein-1 and glucose-6
      phosphate dehydrogenase than did rats fed casein. However, concentrations of
      plasma and VLDL triacylglycerols in rats fed pork protein were not as low as
      those observed in rats fed soy protein. CONCLUSION: Proteins isolated from beef,
      pork, or turkey meat do not differ from casein in their effects on cholesterol
      metabolism. Pork protein decreases plasma triacylglycerol concentrations compared
      with casein but not compared with soy protein. The triacylglycerol-lowering
      effect of pork protein compared with casein is suggested to be caused by
      decreased hepatic fatty acid synthesis.

PMID- 16979323
TI  - Usefulness of oral mucosal epithelial cell apoptosis rate in nutritional
      assessment.
AB  - OBJECTIVE: This preliminary study was designed to explore a new method for
      nutritional assessment by measuring oral mucosal cell apoptosis or proliferation.
      METHODS: Forty-two consecutive patients with gastrointestinal malignant tumors
      were hospitalized on the surgical wards and studied prospectively. Patient
      Generated Subjective Global Assessment was used to identify malnourished
      patients. Anthropometric measurements including weight, body mass index, triceps
      skinfold thickness, and midarm muscle circumference were recorded. The serum
      proteins measured were retinol-binding protein (RBP), transferrin, prealbumin
      (PA), and albumin. Simultaneously, the rates of oral epithelial cell apoptosis
      and proliferation were measured by flow cytometry. Of the 20 malnourished
      patients, 14 were followed up in a serial study with a 3-d nutritional support
      therapy. Nutritional indices and oral epithelial cell apoptosis rate were
      measured after 3 d of nutritional support. RESULTS: Malnutrition was diagnosed in
      20 of 42 patients (47.6%). Oral epithelial apoptosis and proliferation rates were
      significantly decreased (P < 0.01 and P < 0.05, respectively) in malnourished
      compared with non-malnourished patients, although there were no significant
      differences between their anthropometric data. Malnourished patients had lower
      serum levels of RBP, albumin, and PA and rates of oral epithelial cell apoptosis
      and proliferation. The rate of oral epithelial cell apoptosis positively
      correlated with serum RBP (R = 0.32, P < 0.05) and PA (R = 0.33, P < 0.05). The
      rate of oral epithelial cell apoptosis and serum RBP and PA increased
      significantly in the malnourished patients who received nutritional support for 3
      days. CONCLUSIONS: Measuring the rate of oral epithelial cell apoptosis may be
      another non-invasive technique to determine nutritional assessment and is worthy
      of further exploration.

PMID- 16979324
TI  - Formula delivery in patients receiving enteral tube feeding on general hospital
      wards: the impact of nasogastric extubation and diarrhea.
AB  - OBJECTIVE: In contrast to the intensive care unit, little is known of the
      percentage of formula delivered to patients receiving enteral tube feeding (ETF)
      on general wards or of the complications that affect its delivery. This study
      prospectively investigated the incidence of nasogastric extubation and diarrhea
      in patients starting ETF on general wards and examined their effect on formula
      delivery. METHODS: In a prospective observational study, the volume of formula
      delivered to patients receiving ETF on general wards was compared with the volume
      prescribed. The incidence of nasogastric extubation and diarrhea was measured and
      its effect on formula delivery calculated. RESULTS: Twenty-eight patients were
      monitored for a total of 319 patient days. The mean +/- SD volume of formula
      prescribed was 1460 +/- 213 mL/d, whereas the mean volume delivered was only 1280
      +/- 418 mL/d (P < 0.001), representing a mean percentage delivery of 88 +/- 25%
      of prescribed formula. Nasogastric extubation occurred in 17 of 28 patients
      (60%), affecting 53 of the 319 patient days (17%). The percentage of formula
      delivered on days when the nasogastric tube remained in situ was 96 +/- 12% and
      on days when nasogastric extubation occurred it was only 45 +/- 31% (P < 0.001).
      Diarrhea affected 39 of 319 patient days (12%) but there was no difference in
      formula delivery on days when diarrhea did or did not occur (78% versus 89%, P =
      0.295). There was a significant, albeit small, negative correlation between the
      daily stool score and formula delivery (correlation coefficient -0.216, P <
      0.001). CONCLUSIONS: Formula delivery is marginally suboptimal in patients
      receiving ETF on general wards. Nasogastric extubation is common and results in
      an inherent cessation of ETF until the nasogastric tube is replaced and is
      therefore a major factor impeding formula delivery. Diarrhea is also common but
      does not result in significant reductions in formula delivery.

PMID- 16979325
TI  - Investigation on the relationship of proline with wheat anti-drought under soil
      water deficits.
AB  - Proline (content) is closely with plant anti-drought, especially under soil water
      deficits. Many reports from crops and other plants have proved this. Wheat is the
      second important crop on the globe, whose research in this aspect of importance
      for food quality, safety, and yield in field. The related difference in
      physiological indicators and proline content for different soil water treatments
      among wheat with different genotypes is not clear, which has limited deep study
      of wheat anti-drought molecular biology and related anti-drought biotechnological
      breeding. Our current study was focused on the physiological relationship of
      proline and different genotype wheat anti-drought under soil water deficits. Main
      results showed that different wheat genotype had different soil water stress
      threshold. Pro content had closed relationship with soil water stress threshold
      and wheat anti-drought. Developmental course also impacted Pro content for
      different wheat genotypes.

PMID- 16979326
TI  - Oligomethylene spacer length dependent interaction of synthetic galactolipids
      incorporated in phospholipid layers with ricin.
AB  - As models of naturally occurring glycolipids, structurally well-determined
      amphiphilic compounds were prepared. The synthetic molecules have beta-D
      galactopyranosyl or alpha-D-mannopyranosyl and two dodecyl groups as terminal
      hydrophilic sugar and hydrophobic hydrocarbon moieties, respectively. The two
      long alkyl chains are connected by 3,5-dioxybenzamide through ether linkages to
      give a lipid analog purified easily due to its absorbance of ultraviolet light.
      In the synthetic glycolipids, the glycoside and lipid parts are covalently bound
      via an oligomethylene spacer. The glycolipids could be easily incorporated into
      liposomes of L-alpha-phosphatidylcholine. The monoglycosyl moiety of the
      synthetic glycolipids possessing a hexamethylene spacer was present on the
      surface of the liposomes and interacted specifically with a lectin to give
      liposomal assemblies. Such agglutination of these liposomes induced by lectins
      was determined by analyses of turbidity and particle size based on dynamic light
      scattering and laser diffraction methods. The other liposomes possessing a
      shorter ethylene or longer decamethylene linker gave few lectin-induced
      agglutinates, indicating that these spacers were not effective for the
      presentation of the galacto-terminal on the liposomal surfaces. Similar spacer
      dependent recognition of ricin with a galactolipid-incorporated phospholipid
      monolayer was confirmed by surface plasmon resonance technique on a substrate.

PMID- 16979327
TI  - Crocus sativus L. (petal) in the treatment of mild-to-moderate depression: a
      double-blind, randomized and placebo-controlled trial.
AB  - Depression is a major worldwide health problem. Indeed, by 2020, depressive
      disorders are estimated to represent the second largest disease burden worldwide.
      Although a variety of pharmaceutical agents are available for the treatment of
      depression, psychiatrists find that many patients cannot tolerate the side
      effects, do not respond adequately, or finally lose their response. Our objective
      was to assess the efficacy of petal of Crocus sativus in the treatment of mild-to
      moderate depression in a 6-week double-blind, placebo-controlled and randomized
      trial. Forty adult outpatients who met the Diagnostic and Statistical Manual of
      Mental Disorders, fourth edition for major depression based on the structured
      clinical interview for DSM IV participated in the trial. In this double-blind,
      placebo-controlled and randomized trial, patients were randomly assigned to
      receive capsule of petal of C. sativus 30 mg/day (BD) (Group 1) and capsule of
      placebo (BD) (Group 2) for a 6-week study. At 6 weeks, petal of C. sativus
      produced a significantly better outcome on Hamilton Depression Rating Scale than
      placebo (d.f.=1, F=16.87, p<0.001). There were no significant differences in the
      two groups in terms of observed side effects. The results of this study indicate
      the efficacy of petal of C. sativus in the treatment of mild-to-moderate
      depression. A large-scale trial is justified.

PMID- 16979328
TI  - Anti-diabetic properties of the Canadian lowbush blueberry Vaccinium
      angustifolium Ait.
AB  - Incidence of type II diabetes is rapidly increasing worldwide. In order to
      identify complementary or alternative approaches to existing medications, we
      studied anti-diabetic properties of Vaccinium angustifolium Ait., a natural
      health product recommended for diabetes treatment in Canada. Ethanol extracts of
      root, stem, leaf, and fruit were tested at 12.5 microg/ml for anti-diabetic
      activity in peripheral tissues and pancreatic beta cells using a variety of cell
      based bioassays. Specifically, we assessed: (1) deoxyglucose uptake in
      differentiated C2C12 muscle cells and 3T3-L1 adipocytes; (2) glucose-stimulated
      insulin secretion (GSIS) in beta TC-tet pancreatic beta cells; (3) beta cell
      proliferation in beta TC-tet cells; (4) lipid accumulation in differentiating 3T3
      L1 cells; (5) protection against glucose toxicity in PC12 cells. Root, stem, and
      leaf extracts significantly enhanced glucose transport in C2C12 cells by 15-25%
      in presence and absence of insulin after 20 h of incubation; no enhancement
      resulted from a 1 h exposure. In 3T3 cells, only the root and stem extracts
      enhanced uptake, and this effect was greater after 1 h than after 20 h; uptake
      was increased by up to 75% in absence of insulin. GSIS was potentiated by a small
      amount in growth-arrested beta TC-tet cells incubated overnight with leaf or stem
      extract. However, fruit extracts were found to increase 3H-thymidine
      incorporation in replicating beta TC-tet cells by 2.8-fold. Lipid accumulation in
      differentiating 3T3-L1 cells was accelerated by root, stem, and leaf extracts by
      as much as 6.5-fold by the end of a 6-day period. Stem, leaf, and fruit extracts
      reduced apoptosis by 20-33% in PC12 cells exposed to elevated glucose for 96 h.
      These results demonstrate that V. angustifolium contains active principles with
      insulin-like and glitazone-like properties, while conferring protection against
      glucose toxicity. Enhancement of proliferation in beta cells may represent
      another potential anti-diabetic property. Extracts of the Canadian blueberry thus
      show promise for use as a complementary anti-diabetic therapy.

PMID- 16979329
TI  - Short-term, increasing dietary protein and fat moderately affect energy
      expenditure, substrate oxidation and uncoupling protein gene expression in rats.
AB  - Macronutrient composition of diets can influence body-weight development and
      energy balance. We studied the short-term effects of high-protein (HP) and/or
      high-fat (HF) diets on energy expenditure (EE) and uncoupling protein (UCP1-3)
      gene expression. Adult male rats were fed ad libitum with diets containing
      different protein-fat ratios: adequate protein-normal fat (AP-NF): 20% casein, 5%
      fat; adequate protein-high fat (AP-HF): 20% casein, 17% fat; high protein-normal
      fat (HP-NF): 60% casein, 5% fat; high protein-high fat (HP-HF): 60% casein, 17%
      fat. Wheat starch was used for adjustment of energy content. After 4 days,
      overnight EE and oxygen consumption, as measured by indirect calorimetry, were
      higher and body-weight gain was lower in rats fed with HP diets as compared with
      rats fed diets with adequate protein content (P<.05). Exchanging carbohydrates by
      protein increased fat oxidation in HF diet fed groups. The UCP1 mRNA expression
      in brown adipose tissue was not significantly different in HP diet fed groups as
      compared with AP diet fed groups. Expression of different homologues of UCPs
      positively correlated with nighttime oxygen consumption and EE. Moreover, dietary
      protein and fat distinctly influenced liver UCP2 and skeletal muscle UCP3 mRNA
      expressions. These findings demonstrated that a 4-day ad libitum high dietary
      protein exposure influences energy balance in rats. A function of UCPs in energy
      balance and dissipating food energy was suggested. Future experiments are focused
      on the regulation of UCP gene expression by dietary protein, which could be
      important for body-weight management.

PMID- 16979330
TI  - Detection of single-base mismatch at distal end of DNA duplex by electrochemical
      impedance spectroscopy.
AB  - Herein, we report an anomalous electrochemical behavior of surface-bound DNA
      duplex that has single-base mismatches at its distal end. Single-stranded 15-base
      DNA was immobilized at its 5'end onto gold electrode surfaces. After
      hybridization with complementary or mismatched DNA, electrochemical impedance
      spectra were obtained using [Fe(CN)(6)]3-/4- as redox marker ions. Hybridization
      with the complementary DNA reduced the charge-transfer resistance (R(CT)),
      whereas single-base mismatches at the distal end of the duplex largely increased
      the R(CT). This anomaly was found only with the distal end: the increase in R(CT)
      was not observed for mismatches at either the middle or the proximal end. These
      results indicate that electrochemical detection of single-base alterations at an
      end of sample DNA is exceptionally easy because of the diametrically opposite
      responses. This detection principle is promising for the typing of single
      nucleotide polymorphisms in combination with the single-base primer extension
      protocol.

PMID- 16979332
TI  - Adhesion of eukaryotic cell lines on the gold surface modified with extracellular
      matrix proteins monitored by the piezoelectric sensor.
AB  - The piezoelectric sensor (quartz crystal microbalance, QCM) was used to monitor
      cell adhesion in real time. Two cell lines, rat epithelial cells (WB F344) and
      lung melanoma cells (B16F10) were used. The cells were adhered and grown on the
      gold surface of the sensor pre-coated with adsorbed layer of extracellular matrix
      proteins as vitronectin and laminin. The process of cell attachment and spreading
      on the gold surface was continuously monitored and displayed by changes of the
      resonant frequency Deltaf and resistance DeltaR values of the piezoelectric
      resonators. The initial phase of cell attachment and spreading induced a decrease
      of frequency and increase of resistance relating viscoelastic properties of the
      cell monolayer on the sensing surface. The steady-state of both shifts was
      achieved after a few hours. The presence and state of cells on the surface was
      confirmed by fluorescent microscopy. The obtained results demonstrate that the
      piezoelectric sensor is suitable for studies of the cell adhesion processes. Thus
      obtained cell-based biosensor has potential for identification and screening of
      biologically active drugs and other biomolecules affecting cellular shape and
      attachment.

PMID- 16979333
TI  - SECM visualization of spatial variability of enzyme-polymer spots. 1.
      Discretisation and interference elimination using artificial neural networks.
AB  - Enzyme-polymer layers immobilized on an electrode surface often serve as basis
      for amperometric biosensors. Caused by the formation process they show spatial
      variability in the polymer thickness which corresponds to a variability of
      immobilized enzyme activity. The relationship between topography and localized
      enzymatic activity of enzyme-polymer spots was studied using scanning
      electrochemical microscopy (SECM) in the feedback mode and generator-collector
      mode. Discretisation with a grid size corresponding to the scanning parameters
      defined substructures which can be treated as individual microsensors with
      specific response characteristics. The local responses are mainly governed by the
      polymer thickness but also influenced by neighbouring sites. Thus, discretisation
      allowed us to treat an enzyme-polymer spot with dimensions of about 300 microm
      diameter like an array of more than 400 individual microsensors. Using suitable
      selection criteria and multivariate calibration it was possible to identify
      sensing sites which are optimal for the determination of glucose. It was
      demonstrated that an artificial neural network which was trained with the data
      provided by SECM images well predicted glucose concentration in the presence of
      ascorbic acid.

PMID- 16979334
TI  - Human glycogene cloning: focus on beta 3-glycosyltransferase and beta 4
      glycosyltransferase families.
AB  - Glycogenes encode proteins involved in glycan synthesis, such as
      glycosyltransferases, sulfotransferases and sugar-nucleotide transporters. The
      comprehensive identification and functional analysis of human glycogenes has been
      ongoing for some time. During the past 20 years, 183 human glycogenes have been
      cloned and their substrate specificities analyzed. All current information on
      these human glycogenes and their links with orthologous genes in other species is
      summarized in the GlycoGene database. In recent years, two glycogene families,
      beta3-glycosyltransferases and beta4-glycosyltransferases, have been identified
      and analyzed in particular detail.

PMID- 16979335
TI  - Characterization of the canine 3beta-hydroxysteroid dehydrogenase and its
      expression in the corpus luteum during diestrus.
AB  - 3beta-Hydroxysteroid dehydrogenase (3betaHSD) is a key enzyme in the synthesis of
      bioactive steroid hormones. Objectives of the present study were to clone canine
      3betaHSD and to investigate its expression in dog corpora lutea (CL) covering the
      periods of their formation, early and late regression (days 5, 15, 25, 35, 45, 65
      after ovulation). Complete complementary DNA sequence was amplified by RACE PCR.
      Subsequent cloning revealed that the canine ovarian 3betaHSD transcript was
      composed of a 5'-untranslated region (5'-UTR) of 126 nucleotides, an open reading
      frame (ORF) of 1122 nucleotides and a 3'-UTR of 441 nucleotides. The putative ORF
      encoded a 374 amino acid protein which remains highly conserved (79-85% identity)
      between species. The transient expression of the cloned canine 3betaHSD in a
      mammalian heterologous cell expression system (HEK293T cells) identified the
      3betaHSD activity as the only activity of this canine enzyme (absence of any
      detectable 17-hydroxysteroid dehydrogenase activity). Qualitative RT-PCR revealed
      expression of 3betaHSD on all days investigated and the signals were strongest on
      days 5 and 15, with day 25 intensity tending to decrease. However, variability
      between individual animals was high. The significant decrease in the expression
      of 3betaHSD towards the end of diestrus as indicated by Real Time PCR (p<0.01)
      and immunhistochemistry may indicate that the provision of progesterone is
      controlled by availability of the enzyme rather than the substrate.

PMID- 16979336
TI  - Synthesis of D-labeled naphthyliodoacetamide and application to quantitative
      peptide analysis by isotope differential mass spectrometry.
AB  - D-labeled and -unlabeled N-beta-naphthyliodoacetamides have been synthesized for
      specific modification of the sulfhydryl groups of cysteine residues in proteins
      or peptides, and have been applied to quantitative analysis of several peptides.
      A combination of these reagents, coupled with mass spectrometry, is anticipated
      to serve as a useful tool for quantitative analysis of peptides and hence
      proteins.

PMID- 16979337
TI  - Rapid synthesis of 4-benzylidene and 4-[bis-(4-methoxyphenyl)-methylene-2
      substituted phenyl-benzopyrans as potential selective estrogen receptor
      modulators (SERMs) using McMurry coupling reaction.
AB  - 7-Methoxy-4-(4-methoxybenzylidene)-2-substituted phenyl-benzopyrans I and 4-[bis
      (4-methoxyphenyl)-methylene-2-substituted phenyl-benzopyrans II carrying
      different alkylamino residues, designed as estrogen receptor (ER) binding
      ligands, were successfully synthesized through the McMurry coupling reaction of
      substituted benzaldehyde/substituted benzophenones and 2-hydroxyphenyl-7-methoxy
      chroman-4-one in presence of lithium aluminum hydride and titanium (IV) chloride
      (LAH-TiCl(4)). Self-coupling of carbonyl reactants led to the formation of
      several side products. The prototypes were evaluated for their relative binding
      affinity (RBA), as well as their estrogenic and antiestrogenic activities. High
      order of estrogenic activity (>50% gain) observed with compounds 3, 7a, 7b, 7c,
      8, and 10a and also their partial estrogen antagonistic activity (> or =15%) at
      the uterine level points toward successful designing of the compounds. Compounds
      4, 7a, 7b, 7c, and 10a also possessed significant anticancer activity against
      human adenocarcinoma cell line (MCF-7 cell line) that may be related to their
      estrogen-dependent action.

PMID- 16979338
TI  - 'Irreversible' slow-onset inhibition of orotate phosphoribosyltransferase by an
      amidrazone phosphate transition-state mimic.
AB  - A mimic of the putative transition-state intermediate has been synthesized and
      found to be a very slow-onset inhibitor of yeast orotate
      phosphoribosyltransferase. The mechanism of inhibition may involve a rate
      determining isomerization of the enzyme to a form receptive to the inhibitor,
      which then remains tightly bound.

PMID- 16979339
TI  - Synthesis and biological study of 4-aminopyrimidine-5-carboxaldehyde oximes as
      antiproliferative VEGFR-2 inhibitors.
AB  - A novel 4-aminopyrimidine-5-carboxaldehyde oxime scaffold with inhibitory
      activity against VEGFR-2 kinase has been identified. With a 4-fluoro-2
      methylindol-5-yloxy group at the 6-position and alkyl groups as the oxime side
      chains, many analogues showed good potency for VEGFR-2. This series also
      exhibited antiproliferative activity against cancer cells, causing cell
      accumulation at the G2/M phase of the cell cycle and preventing cells from
      entering mitosis. Described here are the chemistry, structure-activity
      relationships (SAR), and biological testing for this series.

PMID- 16979340
TI  - Enzyme inhibition potency enhancement by active site metal chelating and hydrogen
      bonding induced conformation-restricted cyclopropanecarbonyl derivatives.
AB  - Two cyclopropanecarbonyl derivatives were independently found to be 15 and 14
      times more potent than the corresponding isopropylcarbonyl analogues as
      inhibitors of 4-hydroxyphenylpyruvate dioxygenase and dihydroorotate
      dehydrogenase, respectively. A thorough examination of the co-crystal structures
      of available enzyme inhibitor complexes and the conformation of X-ray crystal
      structures of several synthesized cyclopropanecarbonyl derivatives revealed that
      this enhancement by one order of magnitude of inhibition potency exhibited by
      cyclopropanecarbonyl derivatives in both enzymes is probably caused by respective
      metal chelating and hydrogen bonding interactions at the ligand-receptor binding
      site. These specific interactions subsequently cause the cyclopropyl group of the
      molecules to adopt a fixed bisected conformation, which is unavailable for
      isopropylcarbonyl derivatives.

PMID- 16979341
TI  - Pyridine-2-propanoic acids: Discovery of dual PPARalpha/gamma agonists as
      antidiabetic agents.
AB  - A series of novel pyridine-2-propanoic acids was synthesized. A structure
      activity relationship study of these compounds led to the identification of
      potent dual PPARalpha/gamma agonists with varied isoform selectivity. Based on
      the results of efficacy studies in diabetic (db/db) mice, and the desired
      pharmacokinetic parameters, compound (S)-13 was selected for further profiling.

PMID- 16979342
TI  - Synthesis and evaluation of a new series of substituted acyl(thio)urea and
      thiadiazolo [2,3-a] pyrimidine derivatives as potent inhibitors of influenza
      virus neuraminidase.
AB  - A series of substituted acyl(thio)urea and 2H-1,2,4-thiadiazolo [2,3-a]
      pyrimidine derivatives were prepared and both of their cell culture and enzymatic
      activity toward influenza virus were tested. Their in vitro neuraminidase
      inhibitory activities were in good agreement with the corresponding activities in
      cultured cells and they were evaluated as potent neuraminidase inhibitors. Of the
      analogues that demonstrated IC(50)s<0.1microM, 16 and 60 were further
      investigated as candidates with the most potential for future development. The
      molecular docking work of the representative compound was described to provide
      more insight into their mechanism of action and further rationalize the
      observations of this new series herein, which represents a novel class of highly
      potent and selective inhibitors of influenza virus.

PMID- 16979343
TI  - A practical method for determining organ dose during CT examination.
AB  - A practical method, based on depth dose, for determining organ dose during
      computed tomography (CT) examination is presented. For 4-slice spiral CT scans,
      performed at radii of 0, 37.5, 75.0, 112.5, and 150.0 mm, measurement of depth
      dose has been made using thermoluminescent dosimeters (TLDs) inserted into a
      modified International Electrotechnical Commission (IEC) standard dosimetry
      phantom and also additional TLDs placed on the surface of the phantom. A
      regression equation-linking dose with distance from the center of the phantom has
      been formulated, from which dose to a point of interest relative to the surface
      dose can also be calculated. The approximation reflects the attenuation
      properties of X-rays in the phantom. Using the equation, an estimate of organ
      dose can be ascertained for CT examination, assuming water equivalence of human
      tissue and a known organ position and volume. Using the 4-slice spiral scanner,
      relative doses to a patients' lung have been calculated, the location and size of
      the lung in vivo being found from the CT scan image, and the lung being divided
      into 38 segments to calculate the relative dose. Results from our test case show
      the dose to the lung to have been 69+/-13% of surface dose.

PMID- 16979344
TI  - Intra-pericardial hydatid cyst seen by dynamic computed tomography.

PMID- 16979345
TI  - Bactericidal effect of malachite green and red laser on Actinobacillus
      actinomycetemcomitans.
AB  - The aim of this study was to investigate the ability of malachite green (MG)
      combined with a low-power red laser to kill Actinobacillus actinomycetemcomitans
      and to investigate MG photodegradation after photodynamic therapy (PDT) by
      optical absorption spectroscopy. The etiology of periodontal disease is that
      microorganisms form a bacterial biofilm on the surface of the teeth. It is an
      infectious disease and A. actinomycetemcomitans is considered an important agent
      in biofilm ecology. Instead of using antibiotics, PDT is an alternative approach
      to eradicate bacteria. Cultures of A. actinomycetemcomitans were exposed to a 30
      mW diode red laser, in the presence or absence of MG. A group of cultures was
      treated in dark conditions in the presence of MG (0.01% w/v) for 5 min. In the
      presence of MG, two exposure times for laser irradiation were used: t=3 min
      (energy dose=5.4 J/cm(2)), and t=5 min (energy dose=9 J/cm(2)). The samples were
      diluted and bacterial colonies were counted and converted into colony forming
      units. Absorption spectra of the bacterial suspensions, MG, MG-stained bacterial
      suspensions, and photosensitized bacterial suspensions were obtained. A.
      actinomycetemcomitans can be photoinactivated by a red laser in the presence of
      MG. Significant differences were observed between the two energy doses used
      (p<0.05). Red laser alone and MG alone were not able to kill bacteria. Optical
      absorption showed that MG is photobleached after irradiation. These results
      indicate that A. actinomycetemcomitans can be photosensitized by red laser
      combined with MG and that the dye is photodegraded following irradiation.

PMID- 16979346
TI  - Effect of nanoparticle size on the extravasation and the photothrombic activity
      of meso(p-tetracarboxyphenyl)porphyrin.
AB  - Particle size should be optimized to achieve targeted and extended drug delivery
      to the affected tissues. We describe here the effects of the mean particle size
      on the pharmacokinetics and photothrombic activity of meso
      tetra(carboxyphenyl)porphyrin (TCPP), which is encapsulated into biodegradable
      nanoparticles based on poly(d,l-lactic acid). Four batches of nanoparticles with
      different mean sizes ranging from 121 to 343 nm, were prepared using the
      emulsification-diffusion technique. The extravasations of each TCPP-loaded
      nanoparticle formulation from blood vessels were measured, as well as the extent
      of photochemically induced vascular occlusion. These preclinical tests were
      carried out in the chorioallantoic membrane (CAM) of the chicken's embryo.
      Fluorescence microscopy showed that both the effective leakage of TCPP from the
      CAM blood vessels and its photothrombic efficiency were dependent on the size of
      the nanoparticle drug carrier. Indeed, the TCPP fluorescence contrast between the
      blood vessels and the surrounding tissue increased at the applied conditions,
      when the particle size decreased. This suggests that large nanoparticles are more
      rapidly eliminated from the bloodstream. In addition, after injection of a drug
      dose of 1mg/kg body weight and a drug-light application interval of 1 min,
      irradiation with a fluence of 10J/cm(2) showed that the extent of vascular damage
      gradually decreased when the particle size increased. The highest photothrombic
      efficiency was observed when using the TCPP-loaded nanoparticles batch with a
      mean diameter of 121 nm. Thus, in this range of applied conditions, for the
      treatment of for instance a disease like choroidal neovascularization (CNV)
      associated with age-related macular degeneration (AMD), these experiments suggest
      that the smallest nanoparticles may be considered as the optimal formulation
      since they exhibited the greatest extent of vascular thrombosis as well as the
      lowest extravasation.

PMID- 16979348
TI  - Controlled 2D crystallization of membrane proteins using methyl-beta
      cyclodextrin.
AB  - High-resolution structural data of membrane proteins can be obtained by studying
      2D crystals by electron crystallography. Finding the right conditions to produce
      these crystals is one of the major bottlenecks encountered in 2D crystallography.
      Many reviews address 2D crystallization techniques in attempts to provide
      guidelines for crystallographers. Several techniques including new approaches to
      remove detergent like the biobeads technique and the development of dedicated
      devices have been described (dialysis and dilution machines). In addition, 2D
      crystallization at interfaces has been studied, the most prominent method being
      the 2D crystallization at the lipid monolayer. A new approach based on detergent
      complexation by cyclodextrins is presented in this paper. To prove the ability of
      cyclodextrins to remove detergent from ternary mixtures (lipid, detergent and
      protein) in order to get 2D crystals, this method has been tested with OmpF, a
      typical beta-barrel protein, and with SoPIP2;1, a typical alpha-helical protein.
      Experiments over different time ranges were performed to analyze the kinetic
      effects of detergent removal with cyclodextrins on the formation of 2D crystals.
      The quality of the produced crystals was assessed with negative stain electron
      microscopy, cryo-electron microscopy and diffraction. Both proteins yielded
      crystals comparable in quality to previous crystallization reports.

PMID- 16979347
TI  - Regulation of pancreatic secretion in vitro by nociceptin/orphanin FQ and opioid
      receptors: a comparative study.
AB  - The effects of nociceptin/orphanin FQ (N/OFQ) on gastrointestinal functions
      resemble those of classic analgesic opioid agonists. In this study, we compared
      changes in amylase release from guinea pig isolated pancreatic acini and lobules
      induced by the N/OFQ analogue [Arg(14),Lys(15)]N/OFQ and by the delta-receptor
      opioid agonist deltorphin. Carbachol strongly stimulated amylase release from
      isolated acini. Both peptides left baseline and carbachol-stimulated amylase
      secretion from pancreatic acini unchanged. Co-incubation of KCl-stimulated
      lobules with [Arg(14),Lys(15)]N/OFQ or deltorphin inhibited KCl-induced amylase
      release in a concentration-dependent manner. Although maximal inhibition of
      amylase release by [Arg(14),Lys(15)]N/OFQ and deltorphin had similar amplitude,
      [Arg(14),Lys(15)]N/OFQ was 100-fold more potent than deltorphin on a molar basis.
      The selective NOP-receptor antagonist [Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2) (UFP
      101) antagonized [Arg(14),Lys(15)]N/OFQ-induced inhibition but left deltorphin
      induced inhibition unchanged. The selective delta opiate receptor antagonist
      naltrindole had no effect on [Arg(14),Lys(15)]N/OFQ inhibition but partly
      prevented the inhibition by deltorphin. [Arg(14),Lys(15)]N/OFQ and deltorphin
      combined had no influence on each other. These findings show that
      [Arg(14),Lys(15)]N/OFQ inhibits pancreatic enzyme secretion by suppressing
      cholinergic transmission in intralobular nerve fibers, as previously reported for
      opioid agents. They suggest that [Arg(14),Lys(15)]N/OFQ inhibition of amylase
      release is mediated through the NOP receptor and not through the delta opioid
      receptor. The N/OFQ-NOP receptor system, like the delta opioid system, plays an
      inhibitory role in regulating exocrine pancreatic secretion.

PMID- 16979349
TI  - Organization of the Escherichia coli chromosome into macrodomains and its
      possible functional implications.
AB  - Recent advances in fluorescent microscopy have revealed the non-random
      organization of chromosomes in bacterial cells. In Escherichia coli, segments
      included in two large regions show similar localization patterns allowing the
      definition of two macrodomains centered, respectively, on the centromere-like
      site migS (the Ori domain) and the replication terminus (the Ter domain). A
      genetic system measuring long distance DNA interactions confirmed the macrodomain
      organization of the chromosome and revealed the existence of two additional
      macrodomains flanking the Ter domain. Altogether, the E. coli chromosome appears
      to have an open ring-like conformation. Recent developments regarding various
      stages of chromosome biology such as replication, sister chromatid cohesion,
      segregation, and chromosome choreography, have considerably improved our
      understanding of the coordination of chromosome dynamics with the cell cycle. The
      possible involvement of macrodomains in these various processes is discussed.

PMID- 16979350
TI  - A functional endophenotype for sexual orientation in humans.
AB  - Sexually arousing visual stimuli activate the human reward system and trigger
      sexual behavior. Here we performed event-related fMRI during visual processing of
      sexual core stimuli to pinpoint a neuronal correlate of sexual preference in
      humans. To dissociate gender of the stimulus from sexual preference, we studied
      male and female heterosexual and homosexual volunteers while they viewed sexual
      and nonsexual control stimuli. In contrast to previous work, we used core single
      sex stimuli displaying male and female sexually aroused genitals. Since stimuli
      lacked any additional contextual information, they evoked no activity related to
      neuronal processing of faces, gestures or social interactions. Our prediction was
      that the sexual preference of the observer determines the neuronal responsiveness
      to pure male or female sexual stimuli in the human reward and motor system.
      Consistent with our prediction, the ventral striatum and the centromedian
      thalamus, showed a stronger neuronal response to preferred relative to non
      preferred stimuli. Likewise, the ventral premotor cortex which is a key structure
      for imitative (mirror neurons) and tool-related (canonical neurons) actions
      showed a bilateral sexual preference-specific activation, suggesting that viewing
      sexually aroused genitals of the preferred sex triggers action representations of
      sexual behavior. The neuronal response of the ventral striatum, centromedian
      thalamus and ventral premotor cortex to preferred sexual stimuli was consistent
      across all groups. We propose that this invariant response pattern in core
      regions of the human reward and motor system represents a functional
      endophenotype for sexual orientation independent of the gender of the observer
      and gender of the stimulus.

PMID- 16979351
TI  - Use of a fluorescent substrate for the selective quantification of rat CYP3A in
      the liver and the intestine.
AB  - INTRODUCTION: Quantification of cytochrome P450 is a major issue in the
      development of new drugs. Different assays have been reported, but few are very
      selective for the 3A isoform or cytochrome P450. The benzyloxy-substituted
      lactone cyclooxygenase-2 inhibitor 3-[(3, 4-difluorobenzyl)oxy]-5,5-dimethyl-4-[4
      methylsulfonyl) phenyl] furan-2(5H)-one has recently been used successfully to
      probe isoform 3A of cytochrome P450 in the liver. However, its selectivity for
      the rat isoform remains to be established as well as its applicability in other
      tissue, such as the intestine. The purpose of this study was to ascertain the
      specificity of this substrate for the rat 3A isoform of cytochrome P450 using
      Supersomes and its application in non-hepatic tissue (e.g., intestine). METHODS:
      Specificity of the 3-[(3,4-difluorobenzyl)oxy]-5,5-dimethyl-4-[4
      methylsulfonyl)phenyl] furan-2(5H)-one for the isoform 3A of rat cytochrome P450
      was established by using either isoform-specific inhibitory antibody or
      microsomes expressing only one cytochrome P450 isoform. Activity was assayed in
      rat liver and intestinal microsomal protein preparations. RESULTS: Experiments
      with inhibitory antibodies revealed that in liver and intestinal microsomes, more
      than 90% of the substrate metabolism was inhibited by antibodies against isoform
      3A. Selectivity of the substrate for rat 3A isoform was further determined by
      testing the metabolic activity of various Supersomes preparations. DISCUSSION: In
      conclusion, our results validate the usefulness of 3-[(3,4-difluorobenzyl)oxy]
      5,5-dimethyl-4-[4-methylsulfonyl)phenyl] furan-2(5H)-one as a simple and specific
      substrate to study the activity of the isoform 3A of cytochrome P450 in the rat
      liver and intestine.

PMID- 16979352
TI  - Balance performance in adult epilepsy patients.
AB  - PURPOSE: To evaluate the magnitude of subclinical balance dysfunction in adult
      epilepsy patients and to assess the relative contribution of different variables
      to balance impairment. METHODS: Balance performance was evaluated by computerized
      dynamic platform posturography (CDPP) in 25 adult patients following a
      generalized tonic-clonic seizure (GTCS) and in 11 healthy subjects. RESULTS: The
      GTCS was a breakthrough seizure in 20 patients with epilepsy and a first seizure
      in 5. Seven of the patients had localization-related epilepsy and 13 had
      generalized epilepsy. Mean epilepsy duration was 6.6 years. Nineteen of the
      patients were treated with antiepileptic drugs (AEDs), 16 on monotherapy and
      three on polytherapy. Brain CT scan and EEG abnormalities were found in 7 and 14
      patients, respectively. None of the patients had clinical signs of balance
      dysfunction. Postural function, measured by Sway Index (SI), was worse in the
      patients compared to controls. A lower SI was found in patients who did not
      receive AEDs, had one or two seizures, had a disease duration of less than a year
      and had a generalized epilepsy. CONCLUSIONS: Although the study group was small
      and heterogeneous and only a small number of parameters have reached statistical
      significance, it seems that posturography can be helpful in the evaluation of
      postural stability in adult patients with epilepsy.

PMID- 16979353
TI  - Differential expression of endothelial nitric oxide synthase in coronary and
      cardiac tissue in hypoxic fetal guinea pig hearts.
AB  - OBJECTIVE: The purpose of the present study was to quantify the effect of chronic
      hypoxia on endothelial nitric oxide synthase (eNOS) gene and protein expression
      of fetal coronary artery segments and cardiac tissue of fetal guinea pig hearts.
      METHODS: Time-mated pregnant guinea pigs (term = 65 days) were housed in room air
      (NMX, n = 6) or in a hypoxic chamber containing 10.5% O2 for 14 days (HPX14, n =
      6). At near term (60 days gestation), fetuses were excised from anesthetized
      animals via hysterotomy and hearts were removed and weighed. Both coronary artery
      segments and cardiac ventricle were excised from the same hearts, frozen, and
      stored at -80 C until ready for study. eNOS mRNA was quantified using real-time
      polymerase chain reaction (PCR) based on SYBR Green I labeling (BioRad
      Laboratories, Hercules, CA) using eNOS primers obtained from GeneBank normalized
      to 18S. eNOS proteins were quantified by Western immunoblotting using eNOS
      antibody (1:200) and normalized to normoxic controls. eNOS cell-specific
      localization in the fetal guinea pig heart was performed by double
      immunofluorescence staining. RESULTS: Both coronary artery endothelial cells (EC)
      and cardiomyocytes (CM) but not vascular smooth muscle cells of normoxic hearts
      exhibited positive immunostaining of eNOS protein. Chronic hypoxia significantly
      (P < .05) increased both eNOS mRNA and protein levels of coronary artery segments
      (by 210.6% and 51.4%, respectively) but decreased (P < .05) mRNA and protein of
      cardiac tissue (by 50.0% and 40.6%, respectively) in the same hearts.
      CONCLUSIONS: Chronic fetal hypoxia, after 14 days, induces sustained changes in
      eNOS gene and eNOS protein expression that differ between coronary and cardiac
      tissue in the fetal guinea pig heart. This study suggests that while the
      functional roles of altered eNOS expression in hypoxic fetal hearts remain
      unclear, the site at which eNOS expression is altered may be important in the
      adaptive response of the fetal heart to hypoxia.

PMID- 16979354
TI  - Potential use of the adenosine triphosphate cell viability assay in endometrial
      cancer.
AB  - OBJECTIVE: Adenosine triphosphate cell viability assay (ATP-CVA) was used
      previously to evaluate chemotherapy in uterine cancer cell lines. In this study,
      we have performed the ATP-CVA on endometrial cancer patients to study the
      feasibility of using ATP-CVA in endometrial cancer to determine the intrinsic
      chemosensitivity of the cytotoxic drugs. METHODS: Thirty-three patients with
      endometrial adenocarcinoma who presented for a staging operation were recruited.
      Endometrial cancer samples were obtained at the time of operation. In vitro ATP
      CVA and chemosensitivity testing was performed using cisplatin, carboplatin,
      paclitaxel, etoposide, doxorubicin, 4-epidoxorubicin, and topotecan. RESULTS:
      Thirty-two of the 33 endometrial cancer samples were evaluable for SF50 (survival
      fraction at 50% of the peak plasma concentration [PPC]) using ATP-CVA. The median
      SF50 of carboplatin (0.33) was significantly less than the median SF50 of
      cisplatin (0.71), topotecan (0.93), paclitaxel (0.68), doxorubicin (1.0),
      etoposide (0.70), or 4-epidoxorubicin (0.88) (Wilcoxon signed rank test, P
      <.001). CONCLUSION: This study showed the feasibility of using the ATP-CVA in
      endometrial cancer to determine the intrinsic chemosensitivity of cytotoxic
      drugs.

PMID- 16979355
TI  - Phospholipid scramblase isoform expression in pregnant rat uterus.
AB  - OBJECTIVE: Phospholipid scramblases (PLSCRs), a family of novel membrane
      proteins, facilitate the translocation of aminophospholipids from the inner to
      the exterior leaf of the cell membrane. Four isoforms of PLSCR (PLSCR1-4) have
      been reported in mouse and human. The studies described in this report sought to
      characterize the uterine expression of the PLSCR isoforms in the near-term
      pregnant rat. METHODS: Uterine tissue was obtained from timed-pregnant Sprague
      Dawley rats. Total RNA was isolated, treated with DNase, and used in qualitative
      and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) studies
      utilizing PLCSR isoform PCR primers. A rat spleen cDNA bacteriophage library was
      used as a template for PCR-based sequencing to determine the cDNA and translated
      amino acid sequences for the PLSCR3 and PLSCR4 homologs expressed in rats. The 5'
      and 3' untranslated regions were obtained using 5' and 3' Rapid Amplification of
      cDNA Ends (RACE) techniques. RESULTS: RT-PCR studies confirmed expression of
      PLSCR3 and PLSCR4 in the endometrial and myometrial layers of the pregnant rat
      uterus; in contrast, PLSCR1 and PLSCR2 were not found in uterine tissues. The
      cDNA sequence for the rat PLSCR3 homolog was found to be 1642 nucleotides, having
      92% identity with mouse and 80% with human PLSCR3. The rat PLSCR4 homolog has a
      cDNA sequence of 1879 nucleotides, having an 89% identity with mouse and 72%
      identity with human PLSCR4 homologs. CONCLUSION: The intrauterine expression of
      PLSCR3 and PLSCR4 provides a dynamic mechanism by which aminophospholipid
      translocation can be regulated, thereby modulating the activity of various
      membrane proteins that are involved in inflammation and coagulation-related
      events.

PMID- 16979356
TI  - Lack of site-specific production of decidual alpha-2 macroglobulin in human
      pregnancy.
AB  - BACKGROUND: Alpha-2 Macroglobulin (A2M) is a protease inhibitor that is present
      in both human and rat decidual tissue. In mice, decidual A2M prevents excessive
      trophoblastic invasion; however, its role in human decidual tissue is unknown. It
      is possible that A2M may also influence trophoblast invasion in human pregnancy,
      which would be reflected in increased A2M production in decidua basalis. The aim
      of the current study was to determine and compare A2M production from first
      trimester human decidua basalis and decidua parietalis. METHODS: Human decidual
      tissues were obtained from patients undergoing surgical termination at 9 to 12
      gestational weeks. Strips of decidua basalis and decidua parietalis were obtained
      by uterine curettage under real-time ultrasound guidance. Tissue samples were
      fixed in 10% formalin or snap-frozen for immunohistochemistry and reverse
      transcriptase-polymerase chain reaction (RT-PCR) analysis, respectively. Protein
      and mRNA production between the two sites were compared using the Mann-Whitney U
      test. RESULTS: Paired basal and parietal decidua were analyzed by
      immunohistochemistry (n = 9) and by RT-PCR (n = 10). There was no significant
      difference in A2M mRNA expression between decidua basalis and decidua parietalis
      (P = .5). Immunohistochemical staining intensity for A2M protein was
      significantly higher in basalis than in parietalis (P = .004), but the extent of
      positively stained cells were not significantly different (P = .051). Strong A2M
      staining in decidua basalis was mainly localized in the intracellular storage
      vesicles, which may suggest a role of A2M in this site. CONCLUSIONS: We conclude
      that the expression pattern of A2M in human decidua basalis and decidua
      parietalis is not consistent with an important role of this gene during the
      observed gestational period. Contrary to its role in rodent implantation, A2M is
      probably not involved in regulating human implantation and trophoblastic invasion
      during this gestational window frame.

PMID- 16979357
TI  - Estrogen modulates place learning through estrogen receptors in the hippocampus.
AB  - Moderate elevations in circulating estradiol enhance learning in tasks that tap
      place learning strategies such as those requiring the use of extramaze cues. Use
      of place learning strategies is particularly impaired by damage to the
      hippocampus, a structure shown to be sensitive to estrogen treatments. We have
      shown that direct estrogen infusions into the dorsal hippocampus, and not the
      dorsolateral striatum, enhance place learning, suggesting that the hippocampus
      may be an important modulatory site for the effects of estrogen on place
      learning. The current experiment tested whether the hippocampus is indeed a
      critical site of estrogen modulation through classical estrogen receptors. Young
      adult female Sprague-Dawley rats were ovariectomized for 21 days and given
      systemic injections (0.1 ml) of sesame oil (OIL) or 10 microg of 17beta-estradiol
      benzoate (E2), 48 and 24 h before being trained on a place task. Twenty-four
      hours prior to the first systemic injection, separate groups of rats received
      bilateral hippocampal implants of either the antiestrogen ICI 182,780 (ICI) or
      cholesterol vehicle. Implants were maintained until and throughout training.
      Intrahippocampal ICI reversed the enhancement in place learning seen with
      systemic E2 treatment. Unexpectedly, intrahippocampal ICI in OIL-treated rats
      also enhanced place learning. These data suggest that ICI may have some mixed
      agonist and antagonist effects in the hippocampus and that estrogen enhances
      place learning through activation of estrogen receptors located in the
      hippocampus.

PMID- 16979358
TI  - Evolutionary changes in the fungal carbamoyl-phosphate synthetase small subunit
      gene and its associated upstream open reading frame.
AB  - The Neurospora crassa arg-2 and the Saccharomyces cerevisiae ortholog CPA1 encode
      the arginine-specific carbamoyl-phosphate synthetase (CPS-A) small subunit.
      Arginine decreases synthesis of this subunit through the action of a 5' upstream
      open reading frame in the mRNA that encodes a cis-regulatory element, the
      arginine attenuator peptide (AAP), which stalls ribosomes in response to
      arginine. We performed a comparative analysis of the genomic structure and
      predicted peptide sequence of the AAP and CPS-A small subunit across many fungi.
      Differences at the genomic level included variation in intron number and position
      within the AAP and CPS-A coding regions and differences in known regulatory
      motifs. Although differences exist in AAP sequence, there were three absolutely
      conserved amino acid residues in the predicted peptide, including an aspartic
      acid crucial for arginine-dependent regulation of arg-2 and CPA1. A diverged
      Basidiomycete AAP was shown to retain function as an Arg-specific negative
      regulator of translation.

PMID- 16979359
TI  - A critical assessment of Agrobacterium tumefaciens-mediated transformation as a
      tool for pathogenicity gene discovery in the phytopathogenic fungus Leptosphaeria
      maculans.
AB  - We evaluated the usefulness and robustness of Agrobacterium tumefaciens-mediated
      transformation (ATMT) as a high-throughput transformation tool for pathogenicity
      gene discovery in the filamentous phytopathogen Leptosphaeria maculans. Thermal
      asymmetric interlaced polymerase chain reaction allowed us to amplify the left
      border (LB) flanking sequence in 135 of 400 transformants analysed, and indicated
      a high level of preservation of the T-DNA LB. In addition, T-DNA preferentially
      integrated as a single copy in gene-rich regions of the fungal genome, with a
      probable bias towards intergenic and/or regulatory regions. A total of 53
      transformants out of 1388 (3.8%) showed reproducible pathogenicity defects when
      inoculated on cotyledons of Brassica napus, with diverse altered phenotypes. Co
      segregation of the altered phenotype with the T-DNA integration was observed for
      6 of 12 transformants crossed. If extrapolated to the whole collection, this
      indicates that 1.9% of the collection actually corresponds to tagged
      pathogenicity mutants. The preferential insertion into gene-rich regions along
      with the high ratio of tagged mutants renders ATMT a tool of choice for large
      scale gene discovery in L. maculans.

PMID- 16979360
TI  - Evidence for the dispersal of a unique lineage from Asia to America and Africa in
      the sugarcane fungal pathogen Ustilago scitaminea.
AB  - The basidiomycete Ustilago scitaminea Sydow, which causes sugarcane smut disease,
      has been spreading throughout Africa and America since the 1940s. The genetic
      diversity and structure of different populations of this fungus worldwide was
      investigated using microsatellites. A total of 142 single-teliospore were
      isolated from 77 distinct whips (sori) collected in 15 countries worldwide.
      Mycelium culture derived from on generation of selfing of these single
      teliospores were analysed for their polymorphisms at 17 microsatellite loci. All
      these strains but one were homozygous at all loci, indicating that selfing is
      likely the predominant reproductive mode of U. scitaminea. The genetic diversity
      of either American or African U. scitaminea populations was found to be extremely
      low and all strains belong to a single lineage. This lineage was also found in
      some populations of Asia, where most U. scitaminea genetic diversity was
      detected, suggesting that this fungal species originated from this region. The
      strong founder effect observed in U. scitaminea African and American populations
      suggests that the fungus migrated from Asia to other continents on rare occasions
      through movement of infected plant material.

PMID- 16979361
TI  - [Giving blood and human rights].

PMID- 16979362
TI  - High and inducible expression of human immunodeficiency virus type 1 (HIV-1) Nef
      by adenovirus vector does not disturb potent antigen presentation by monocyte
      derived dendritic cells.
AB  - Numerous studies indicated that Nef is a pleiotropic factor. Although it has been
      shown that Nef impairs the antigen-presenting activity of dendritic cells, more
      recent studies have shown no such impairment. This issue is critical for
      designing a vaccine expressing Nef. To refine our knowledge regarding the effect
      of Nef on dendritic cells, we developed constitutive and inducible adenovirus
      vector systems that express high levels of Nef in monocyte-derived dendritic
      cells (MDDCs). We showed here that Nef expression clearly downregulated CD4
      expression of MDDCs but had little or no effect on other surface molecules,
      including MHC class I. Nef also did not affect the functional maturation of
      MDDCs. Use of the inducible Nef-expression system clearly revealed that
      adenovirus infection per se modulates cytokine secretion and the expression of
      apoptosis-related molecules in MDDCs, whereas Nef had no effect on these
      functions. Moreover, the antigen-presenting activity of MDDCs was not disturbed
      by the presence of Nef. On the contrary, we found that Nef-expressing MDDCs
      generated from HIV-1-infected individuals efficiently activated Nef-reactive T
      cells. Therefore, although adenovirus vector may modulate some aspects of MDDC
      function, Nef-expressing adenovirus would be served as one of HIV vaccine
      candidates.

PMID- 16979363
TI  - A DNA vaccine encoding CCL4/MIP-1beta enhances myocarditis in experimental
      Trypanosoma cruzi infection in rats.
AB  - Chagas' disease, caused by Trypanosoma cruzi, is a major cause of cardiovascular
      disease in Latin America. Exacerbated inflammation disproportional to parasite
      load characterizes chronic myocardial lesions in chagasic patients. Chemokines
      and their receptors are expected to account for the renewed inflammatory
      processes after the inoculation of the parasite, but their potential unique
      functions are far from being clear. Herein, we evaluated the effect of a DNA
      vaccine encoding CCL4/MIP-1beta, a CC-chemokine, in T. cruzi-elicited myocarditis
      in rats. Holtzman rats were given intramuscularly cardiotoxin and the CCL4/MIP
      1beta DNA-containing plasmid (100microg) was delivered in this muscular site four
      times. Fourteen days after last immunization, animals were inoculated with a
      myotropical CL-Brener T. cruzi clone. Peak of parasitism was observed at day 15
      after infection, preceding the peak of myocardial inflammation at day 20.
      Myocarditis was still intense at day 30, but the inflammatory infiltrates showed
      a more focal distribution. The expression of CCL2/MCP-1 and CCL4/MIP-1beta
      correlated closely with the kinetics of myocardial inflammation. The CCL4/MIP
      1beta DNA vaccine induced an increase of the levels of the anti-CCL4/MIP-1beta
      observed in T. cruzi-infected animals. This was associated with an exacerbation
      of myocardial inflammation and fibrosis, although alterations in parasitemia and
      myocardial parasitism were not observed. Our data suggest that CCL4/MIP-1beta
      plays a role in preventing excessive inflammation and pathology rather than in
      controlling parasite replication.

PMID- 16979364
TI  - NKT cells play a limited role in the neutrophilic inflammatory responses and host
      defense to pulmonary infection with Pseudomonas aeruginosa.
AB  - CD1d-restricted NKT cells are reported to play a critical role in the host
      defense to pulmonary infection with Pseudomonas aeruginosa. However, the
      contribution of a major subset expressing a Valpha14-Jalpha18 gene segment
      remains unclear. In the present study, we re-evaluated the role of NKT cells in
      the neutrophilic inflammatory responses and host defense to this infection using
      mice genetically lacking Jalpha18 or CD1d (Jalpha18KO or CD1dKO mice). These mice
      cleared the bacteria in lungs at a comparable level to wild-type (WT) mice. There
      was no significant difference in the local neutrophilic responses, as shown by
      neutrophil counts and synthesis of MIP-2 and TNF-alpha, in either KO mice from
      those in WT mice. Administration of alpha-galactosylceramide, a specific
      activator of Valpha14+ NKT cells, failed to promote the bacterial clearance and
      neutrophilic responses, although the same treatment increased the synthesis of
      IFN-gamma, suggesting the involvement of this cytokine downstream of NKT cells.
      In agreement against this notion, these responses were not further enhanced by
      administration of recombinant IFN-gamma in the infected Jalpha18KO mice. Our data
      indicate that NKT cells play a limited role in the development of neutrophilic
      inflammatory responses and host defense to pulmonary infection with P.
      aeruginosa.

PMID- 16979365
TI  - Protection from murine cysticercosis by immunization with a parasite cysteine
      protease.
AB  - Central nervous system infection by Taenia solium cysts causes
      neurocysticercosis, a common neurological infection in the Third World. We have
      previously isolated cysteine proteases from Taenia crassiceps and T. solium. In
      this study, we immunized BALB/c mice with the purified T. solium cysteine
      protease and challenged them with Taenia crassiceps. Immunized mice had a 72%
      reduction in parasite burden compared to mice that received no immunization.
      Immunized mice developed antigen specific lymphocyte proliferation. These data
      support further studies of the T. solium cysteine protease as a vaccine
      candidate.

PMID- 16979366
TI  - Lagochilascaris minor third-stage larvae secrete metalloproteases with
      specificity for fibrinogen and native collagen.
AB  - Dissemination of parasitic infections depends on migration through tissues and
      evasion from both hemostatic processes and immune responses from hosts.
      Metalloproteases play major roles in these mechanisms of pathogen-host
      interactions and, thus, are considered drug targets. In this study, we
      characterized metalloprotease activities in excretory/secretory (ES) products
      from third stage larvae (L3) of the ascarid Lagochilascaris minor, the causative
      agent of lagochilascariosis, which demonstrates an impressive migrating capacity
      across host tissues, including bone. Gel enzymography showed that ES products of
      L3 display two major gelatinolytic activities. Optimal proteolytic activity was
      found to occur at neutral/alkaline pH and was associated with two L. minor
      secreted metalloproteases of 59 (SM59(Lm)) and 114kDa (SM114(Lm)). We next showed
      that ES products of L3 were able to hydrolyze fibrinogen and collagen I at
      neutral pH, but not BSA, in an extensive manner. Furthermore, we demonstrated
      that ES products of L3 mediate hydrolysis of the triple helical structure of
      collagen I fibers in mouse mesentery. These results suggest that ES proteases of
      L3 might facilitate both L. minor migration through host tissues by hydrolyzing
      collagens of the extracellular matrix and evasion from host hemostatic mechanisms
      by degrading fibrinogen.

PMID- 16979367
TI  - [Subsequent pregnancy following uterine artery embolization for interstitial
      pregnancy].
AB  - Subsequent pregnancy following an interstitial pregnancy is rare. The risk of
      uterine rupture may be increased in this situation. Uterine selective
      embolization has been proposed as an effective treatment. However, no further
      pregnancy has ever been described after this method of management. We are
      reporting a case of subsequent pregnancy following interstitial pregnancy managed
      by embolization. The pregnancy was uneventful. A healthy male infant was
      delivered by C-section. This case supports the hypothesis that selective
      embolization for interstitial pregnancy may respect fertility. However, as actual
      risk of uterine rupture in subsequent pregnancies remains unknown, a C-section is
      advised.

PMID- 16979368
TI  - [Fertiloscopy: Clermont-Ferrand's experiment].
AB  - OBJECTIVE: Evaluation of fertiloscopy's place in the management of female
      infertility. PATIENTS AND METHODS: Retrospective study including 229 women
      presenting primary or secondary infertility without pathology raising of an
      evident surgical sanction and benefitting from a fertiloscopy. Perioperative data
      analysis (context of the infertility, operating technique, complications).
      RESULTS: Two hundred and three fertiloscopic procedures succeeded (88.6%),
      revealing lesions in 58 cases (28.6%) requiring a laparoscopy. These are
      represented by adherences (21 cases), endometriosis (17 cases), an abnormality of
      the tubal permeability (10 cases), complete or partial failure to visualize the
      adnexae (6 cases) and ovarian cysts visualization (4 cases). Five complications
      (2.5%) without major consequence will be deplored: two rectal injuries, two
      hemorrhagic complications and a postoperative salpingitis. Most of procedures
      (97.5%) have been performed in an ambulatory setting except when a geographic
      remoteness did not allow it (5 patients). DISCUSSION AND CONCLUSION: Fertiloscopy
      is a safe and reliable procedure. It can be substituted to laparoscopy in the
      routine assessment of infertile women management in case of not obvious surgical
      indication.

PMID- 16979369
TI  - [Molecular anomalies of the Y chromosome: Consequences on male fertility].
AB  - Molecular anomalies of the Y chromosome leading to male infertility are mainly
      microdeletions of the long arm of the Y chromosome. Three recurrently deleted
      portions of the long arm are the AZFa, AZFb and AZFc (AZF: Azoospermia Factor)
      regions. Complete deletions of the AZFc region are found in 10% of cases of
      severe male infertility. In addition to the AZF deletions, certain classes of Y
      chromosome (haplogroups) may also predispose to male infertility and could be
      transmitted to future male descents by various Assisted Reproductive Techniques
      (ART). Since the first discovery of microdeletions, the sequence of the Y
      chromosome has become available, revealing the mechanisms underlying deletion
      formation and also resulting in a coherent screening strategy. Recently, partial
      deletions of the AZF regions have been described. The significance of these
      deletions in the clinical context remains to be defined.

PMID- 16979370
TI  - Staining of wool using the reaction products of ABTS oxidation by laccase:
      synergetic effects of ultrasound and cyclic voltammetry.
AB  - The effects of ultrasound on 2,2'-Azinobis(3-ethylbenzothiazoline-6-sulfonate)
      enzymatic oxidation by laccase (Trametes villosa) has been studied by means of
      cyclic voltammetry. The reaction was allowed to proceed in the presence of a
      piece of wool and the coloration depth of the wool fabric was measured by means
      of K/S. It was observed that cyclic voltammetry is influenced the dyeing process
      and higher K/S values were obtained when the cyclic voltammetry was combined with
      the ultrasonic irradiation. Moreover, the K/S value is the sum of the values
      obtained when the wool staining is done in just the presence of cyclic
      voltammetry or in just the presence of ultrasound. The results obtained on the
      indigo carmine decolourization gives information on the importance of controlling
      the amount of ABTS(+) formed during the ultrasonication process.

PMID- 16979371
TI  - Purification and characterization of C-terminal truncated forms of histone H2A in
      monocytic THP-1 cells.
AB  - Histones are key components of chromatin. We investigated histone H2A
      immunoreactive proteins in acute monocytic leukemia THP-1 cells using three
      polyclonal antibodies raised against peptides corresponding to distinct regions
      of H2A. Two unknown immunoreactive proteins (9- and 12-kDa proteins), H2A (14kDa)
      and ubiquitinated H2A (23kDa) were found in the cell lysates prepared by
      immediate direct addition of SDS-PAGE sample buffer to the cells as well as in
      the nuclear and chromatin fractions. However, they were not found in the
      cytoplasmic fraction. The unknown proteins were successfully purified by
      immunoaffinity chromatography from the cell nucleus extract and identified as 9
      kDa H2A(1-87) and 12-kDa H2A(1-114), suggesting that both were produced by
      limited proteolysis of intact H2A(1-129). The truncated forms of H2A probably
      persisted as chromatin constituents, since the stability of H2A(1-87) in the
      chromatin fraction was sensitive to treatment with micrococcal nuclease, and
      H2A(1-114) was solubilized with lower ionic strength from the chromatin fraction
      obtained by micrococcal nuclease treatment. Truncated H2A proteins in THP-1 cells
      were transiently increased in amount by short-term treatment with phorbol 12
      myristate 13-acetate or all-trans-retinoic acid, both of which induce macrophage
      like differentiation. Furthermore, these increases were suppressed by preceding
      treatment with carbobenzoxy-l-leucyl-l-leucyl-l-leucinal (MG132) but not with
      carbobenzoxy-l-isoleucyl-gamma-t-butyl-l-glutamyl-l-alanyl-l-leucinal (PSI), both
      of which are generally known as proteasome inhibitors. Our results suggest that
      histone H2A is cleaved at least at two sites by protease(s) that remain obscure,
      and might affect chromatins in the early stage of THP-1 cell differentiation.

PMID- 16979372
TI  - Foot-and-mouth disease virus 3C protease: recent structural and functional
      insights into an antiviral target.
AB  - The 3C protease from foot-and-mouth disease virus (FMDV 3C(pro)) is critical for
      viral pathogenesis, having vital roles in both the processing of the polyprotein
      precursor and RNA replication. Although recent structural and functional studies
      have revealed new insights into the mechanism and function of the enzyme, key
      questions remain that must be addressed before the potential of FMDV 3C(pro) as
      an antiviral drug target can be realised.

PMID- 16979373
TI  - Intra-oral minor salivary gland tumors: a clinicopathological study of 546 cases.
AB  - Salivary gland tumors are uncommon and most reported series include tumors
      affecting both major and minor glands. Very few series have focused solely on
      intra-oral minor salivary gland tumors. The aim of this study is to report the
      clinicopathological data of intra-oral minor salivary gland tumors in our oral
      biopsy files during the last 14 years. A total of 546 minor salivary gland
      tumors, including 305 benign (55.9%) and 241 malignant (44.1%) lesions, were
      reviewed. The two most common tumors were pleomorphic adenoma (181 cases, 33.2%)
      and mucoepidermoid carcinoma (125 cases, 22.9%), and the most commonly affected
      site was the palate (181 cases, 33.2%). The highest incidence was found in
      patients in the 5-7th decade of life, and females were more commonly affected
      than males in the vast majority of various histological types of tumors. Large
      series of intra-oral minor salivary gland tumors help to understand their
      clinical and pathological aspects and consequently their proper management and
      prognosis.

PMID- 16979374
TI  - Decrease in mast cells in oral squamous cell carcinoma: possible failure in the
      migration of these cells.
AB  - It is becoming accepted that multiple cell types in stromal microenvironment are
      involved in tumorigenesis. In this setting, mast cells (MC) display a diversity
      of roles that may contribute to the defense against tumors or tumor progression.
      Thus, the aim of this study was to evaluate density and migration of MCs in OSCC
      (oral squamous cell carcinoma) and pre-malignant oral hyperkeratosis
      (leukoplakia) as well as their relationship with clinical and microscopic
      parameters. The tryptase and c-kit expression was analyzed in 38 cases of OSCC,
      26 cases of leukoplakia, and 12 cases of clinically healthy oral mucosa (control)
      by means of immunohistochemistry. The tryptase(+) cell numbers were decreased in
      OSCC (P=0.0003) and leukoplakia (P=0.03) compared with control. Similar numbers
      of tryptase(+) cells were observed in leukoplakia and OSCC (P=0.31). The density
      of c-kit(+) MCs was also significantly lower in OSCC and leukoplakia in relation
      to control resulting in a reduced c-kit(+)/tryptase(+) relationship in OSCC (19%)
      in comparison with leukoplakia (59%) and control (63%). No correlation was
      observed between MC populations with clinical and microscopic characteristics of
      OSCC. Our findings suggest that the decrease in MC numbers in pre-malignant and
      malignant oral lesions may be related to the migration failure of these cells,
      possibly reflecting an important modification in the microenvironment during
      tumor initiation and progression.

PMID- 16979375
TI  - The random amplified polymorphic DNA (RAPD) assay and related techniques applied
      to genotoxicity and carcinogenesis studies: a critical review.
AB  - More than 9000 papers using the random amplified polymorphic DNA (RAPD) or
      related techniques (e.g. the arbitrarily primed polymerase chain reaction (AP
      PCR)) have been published from 1990 to 2005. The RAPD method has been initially
      used to detect polymorphism in genetic mapping, taxonomy and phylogenetic studies
      and later in genotoxicity and carcinogenesis studies. Despite their extensive
      use, these techniques have also attracted some criticisms, mainly for lack of
      reproducibility. In the light of their widespread applications, the objectives of
      this review are to (1) identify the potential factors affecting the optimisation
      of the RAPD and AP-PCR assays, (2) critically describe and analyse these
      techniques in genotoxicity and carcinogenesis studies, (3) compare the RAPD assay
      with other well used methodologies, (4) further elucidate the impact of DNA
      damage and mutations on the RAPD profiles, and finally (5) provide some
      recommendations/guidelines to further improve the applications of the assays and
      to help the identification of the factors responsible for the RAPD changes. It is
      suggested that after proper optimisation, the RAPD is a reliable, sensitive and
      reproducible assay, has the potential to detect a wide range of DNA damage (e.g.
      DNA adducts, DNA breakage) as well as mutations (point mutations and large
      rearrangements) and therefore can be applied to genotoxicity and carcinogenesis
      studies. Nevertheless, the interpretation of the changes in RAPD profiles is
      difficult since many factors can affect the generation of RAPD profiles. It is
      therefore important that these factors are identified and taken into account
      while using these assays. On the other hand, further analyses of the relevant
      bands generated in RAPD profile allow not only to identify some of the molecular
      events implicated in the genomic instability but also to discover genes playing
      key roles, particularly in the initiation and development of malignancy. Finally,
      to elucidate the potential genotoxic effects of environmental contaminants, a
      powerful strategy could be firstly to use the RAPD assay as a screening method
      and secondly to apply more specific methods measuring for instance DNA adducts,
      gene mutations or cytogenetic effects. It is also envisaged that these assays
      (i.e. RAPD and related techniques), which reflect effects at whole genome level,
      would continue to complement the use of emerging technologies (e.g. microarrays
      which aim to quantify expression of individual genes).

PMID- 16979376
TI  - Regulatory failure of serum prohepcidin levels in patients with hepatitis C.
AB  - BACKGROUND/AIMS: Elevated serum ferritin and hepatic iron concentrations are
      frequently observed in chronic hepatitis C (CHC), which may be related to
      hepcidin. Because the role of hepcidin in CHC patients remains unknown, we aimed
      in this study to generate some information about hepcidin in CHC. METHODS: To
      determine whether serum hepcidin correlates with markers of iron status in
      patients with viral hepatitis, we measured serum prohepcidin levels in patients
      with hepatitis C virus (HCV) and hepatitis B virus (HBV) infection and in healthy
      controls. RESULTS: Serum prohepcidin and ferritin levels were negatively
      correlated (r=-0.182, P=0.037) in HCV patients and positively correlated in HBV
      patients and in healthy controls. The total iron scores in liver specimens from
      HCV patients were also negatively correlated (r=-0.403, P=0.013). Serum
      prohepcidin levels in patients with liver cirrhosis (LC) were significantly lower
      than in patients with chronic hepatitis (CH). In both CH and LC patients, serum
      prohepcidin levels were significantly lower in HCV patients than in HBV patients.
      CONCLUSION: Failure of homeostatic regulation of serum prohepcidin concentrations
      may be induced by HCV infection, resulting in elevation of serum ferritin levels,
      which leads to the progression of liver injury by iron overload in CHC patients.

PMID- 16979378
TI  - The FEV1/FEV6 ratio is a good substitute for the FEV1/FVC ratio in the elderly.
AB  - AIMS: To determine the agreement between the FEV1/FEV6 ratio and the FEV1/FVC
      ratio in an elderly population. METHOD: The study sample consisted of 3874
      participants in a cross-sectional population survey in Tromso, Norway, aged 60
      years or more, in whom acceptable spirometry had been obtained. Mean differences
      between the FEV1/FEV6 ratio (%) and the FEV1/FVC ratio (%) were calculated
      according to age, sex, smoking habit, and the degree of airflow limitation. ROC
      curve analysis and Kappa-statistics were used to estimate the utility of the
      FEV1/FEV6 ratio in predicting an FEV1/FVC ratio < 70%. RESULTS: The mean
      difference between FEV1/FEV6% and FEV1/FVC% was 2.7% in both men and women. The
      difference between the two measures increased somewhat with increasing age, and
      was more pronounced with smoking and decreasing FEV1/FVC ratio. The value for the
      FEV1/FEV6 ratio which best predicted an FEV1/FVC ratio of 70%, was 73%, and a
      very good agreement was found between these two cut-off values (kappa = 0.86).
      CONCLUSION: The FEV1/FEV6 ratio appears to be a good substitute for the FEV1/FVC
      ratio in an elderly population.

PMID- 16979379
TI  - What lies behind relief and worsening of asthma symptoms? A register-based study
      of adults with asthma and other chronic obstructive pulmonary diseases in
      Finland.
AB  - AIMS: To examine how subjects with relief or worsening of asthma symptoms differ
      in terms of gender, age, severity and duration of asthma, comorbidity, and
      difficulties with medication and daily life. METHODS: A postal inquiry among a
      sample of 6000 adults with clinically diagnosed asthma and/or other chronic
      obstructive pulmonary diseases. RESULTS: Relief of asthma symptoms over a 12
      month period was associated with a recent asthma diagnosis, within five years, in
      both sexes. Lack of current smoking and lack of problems in using anti-asthmatic
      treatment were associated with a positive outcome in men, and mild asthma and
      living alone associated with a positive outcome in women. Severe and moderate
      asthma predicted worse symptoms in both sexes, as did other obstructive pulmonary
      diseases, living alone, and medication problems amongst men. CONCLUSIONS:
      Patients with asthma should be cared for comprehensively, requiring consideration
      of both clinical and psychosocial factors that can modify the course of the
      disease.

PMID- 16979380
TI  - Long-acting beta-agonists in adult asthma: Evidence that these drugs are safe.
AB  - If asthma is not controlled with low-dose inhaled corticosteroids (ICS), by far
      the best next step is the addition of a long-acting, inhaled beta-agonist (LABA).
      Questions regarding the safety of this class of drug have been raised. However,
      careful examination of the reports which have caused concern in this regard does
      not reveal any evidence of an increased risk associated with the appropriate use
      (i.e. in combination with an inhaled ICS) of LABAs in asthma. There is much to
      suggest that the adverse outcomes associated with LABA monotherapy have been due
      to "masking of inflammation" rather than a toxic effect of the drugs. In some
      instances, this has likely allowed worsening asthma to be overlooked - with dire
      consequences. Studies in subjects receiving combination therapy with LABAs plus
      ICSs suggest that, if anything, there is an enhanced anti-inflammatory action
      with the LABA/ICS combination superior to that achieved with ICS alone at the
      same dose.

PMID- 16979381
TI  - On the identification of differentially expressed genes: improving the
      generalized F-statistics for Affymetrix microarray gene expression data.
AB  - It has been shown that the generalized F-statistics can give satisfactory
      performances in identifying differentially expressed genes with microarray data.
      However, for some complex diseases, it is still possible to identify a high
      proportion of false positives because of the modest differential expressions of
      disease related genes and the systematic noises of microarrays. The main purpose
      of this study is to develop statistical methods for Affymetrix microarray gene
      expression data so that the impact on false positives from non-expressed genes
      can be reduced. I proposed two novel generalized F-statistics for identifying
      differentially expressed genes and a novel approach for estimating adjusting
      factors. The proposed statistical methods systematically combine filtering of non
      expressed genes and identification of differentially expressed genes. For
      comparison, the discussed statistical methods were applied to an experimental
      data set for a type 2 diabetes study. In both two- and three-sample analyses, the
      proposed statistics showed improvement on the control of false positives.

PMID- 16979382
TI  - An alternatively spliced soluble TNF-alpha receptor is associated with metabolic
      disorders: a replication study.
AB  - In a previous study, we identified a biologically active form of tumor necrosis
      factor-alpha receptor 2 (sTNFR2) produced by differential splicing (DS-TNFR2)
      which antagonized TNF-alpha biological activity. Obesity, insulin resistance and
      type 2 diabetes are linked to increased TNF-alpha action. We hypothesized that
      subjects with detectable DS-TNFR2 would be protected from developing obesity and
      related metabolic disorders. Thus, we investigated if circulating DS-TNFR2
      concentration was associated with components of the so-called metabolic syndrome
      among 269 consecutive subjects from the general population. DS-TNFR2 was measured
      using a monoclonal antibody against an epitope present in TNFR2 (first 14
      residues of the juxtamembrane region) but predicted to be absent in soluble
      proteolytic cleavage-produced TNFR2. Plasma DS-TNFR2 concentration was
      significantly decreased among patients with glucose intolerance or type 2
      diabetes mellitus (p=0.026). DS-TNFR2 tended to be associated with fasting and
      post-load glucose (both r=-0.11, p=0.054), and with diastolic blood pressure in
      men (r=-0.16, p=0.07). Serum DS-TNFR2 concentration was significantly associated
      with LDL cholesterol (r=-0.28, p=0.002), uric acid (r=-0.13, p=0.04) and with
      blood glycated hemoglobin (r=-0.13, p=0.04). DS-TNFR2 declined with increased
      number of components of the metabolic syndrome (p=0.03). Those subjects with 2 or
      more components had significantly decreased circulating DS-TNFR2 levels (0.96+/
      2.2 versus 1.7+/-3.2, p=0.033). In summary, the circulating concentration of DS
      TNFR2 seems to be inversely linked to metabolic disorders, hinting at a possible
      anti-inflammatory role.

PMID- 16979384
TI  - Repeated exposure to low-dose diesel exhaust after allergen challenge exaggerates
      asthmatic responses in mice.
AB  - BACKGROUND: In conjunction with allergens, diesel exhaust particles act as an
      adjuvant to enhance IgE responses, inducing expression of cytokines/chemokines
      and adhesion molecules, and increasing airway hyper-responsiveness (AHR). As most
      studies were designed to expose animals to diesel exhaust throughout the periods
      of both sensitization and allergen challenge, it remains unclear whether diesel
      exhaust (DE) exposure exaggerates airway responses in asthmatic animals.
      OBJECTIVE: To study effects of exposure to low-dose DE on AHR and allergic airway
      inflammation in asthmatic mice. METHODS: BALB/c mice were sensitized by
      intraperitoneal injection of ovalbumin and challenged by intranasal
      administration with ovalbumin. They were exposed to low-dose DE for 7 h/day, 5
      days/week, for up to 12 weeks. AHR to methacholine was evaluated by whole-body
      plethysmography as well as bronchoalveolar lavage cell analysis and cytokine gene
      expression in lungs. RESULTS: Repeated exposure of asthmatic mice to low-dose DE
      resulted in increased AHR and gene expression of several pro-asthmatic
      cytokines/chemokines, but these effects rapidly subsided with continued exposure
      to DE. CONCLUSION: Repeated exposure to low-dose DE after ovalbumin challenge
      exaggerates allergic responses in mice, but effects are not prolonged with
      continuous DE exposure.

PMID- 16979383
TI  - Age-dependent loss of tolerance to an immunodominant epitope of glutamic acid
      decarboxylase in diabetic-prone RIP-B7/DR4 mice.
AB  - We have identified for the first time an age-dependent spontaneous loss of
      tolerance to two self-antigenic epitopes derived from putative diabetes
      associated antigens glutamic acid decarboxylase (GAD65) and glial fibrillary
      acidic protein (GFAP) in RIP-B7/DRB1*0404 HLA transgenic mice. Diabetic and older
      non-diabetic mice exhibited a proliferative response to an immunodominant epitope
      from GAD65 (555-567) and also from GFAP (240-252) but not from an immunogenic
      epitope from diabetes-associated islet-specific glucose-6-phosphatase catalytic
      subunit-related protein. The response to both of these self-antigens is not
      observed in young mice but is observed in older non-diabetic mice and is
      accompanied by histological evidence of insulitis in the absence of overt
      diabetes. Islet infiltrates in older non-diabetic mice and diabetic mice contain
      CD4(+)/FoxP3(+) cells and suggest the presence of a regulatory mechanism prior
      and during diabetic disease. Diabetes penetrance in RIP-B7/DR0404 mice is 23%
      with a mean onset age of 40 weeks and is similar to that reported for RIP
      B7/DR0401 mice. A gender preference is observed in that 38% of female mice become
      diabetic compared to 8% of male mice.

PMID- 16979385
TI  - The internalization route resulting in successful gene expression depends on both
      cell line and polyethylenimine polyplex type.
AB  - Understanding cellular uptake and intracellular processing of nonviral gene
      delivery systems is a key aspect in developing more efficient vectors. In this
      study, the impact of clathrin- and caveolae/lipid-raft-dependent endocytosis on
      cell entry and overall transfection efficiency of polyethylenimine (PEI)
      polyplexes was evaluated. Most remarkably, the internalization pathway mediating
      successful transfection depended on both cell type and polyplex type applied.
      Colocalization studies with transferrin and cholera toxin B revealed that at
      least two specific endocytosis pathways--the clathrin-dependent and the lipid
      raft-dependent--mediated cellular uptake of PEI polyplexes. With the help of
      specific uptake inhibitors (chlorpromazine and filipin III), cell-line-dependent
      variations regarding the route of successful transfection were observed (HUH-7,
      COS-7, HeLa). In COS-7 cells, the clathrin-dependent pathway was the main
      contributor to the transfection process. In HUH-7 cells, gene transfer by linear
      PEI polyplexes succeeded mainly via the clathrin-dependent route, whereas
      transfection by branched PEI polyplexes was mediated by both pathways. In HeLa
      cells, both pathways were able to mediate successful gene delivery. However, the
      lipid-raft-dependent pathway was more relevant. The study also revealed that the
      concentration window between specific inhibitory function and nonspecific
      toxicity of the uptake inhibitors was very narrow.

PMID- 16979386
TI  - Role of colonic fermentation in the perception of colonic distention in irritable
      bowel syndrome and functional bloating.
AB  - BACKGROUND & AIMS: Bloating represents a frequent gastrointestinal symptom, but
      the pathophysiologic mechanism responsible for its onset is still largely
      unknown. Patients very frequently attribute the sensation of bloating to the
      presence of excessive bowel gas, but not all patients with gas-related symptoms
      exhibit increased intestinal production of gas. It is therefore possible that
      other still unrecognized mechanisms might contribute to its pathophysiology. Our
      aim was to evaluate whether a subgroup of patients affected by functional
      abdominal bloating presents hypersensitivity to colonic fermentation. METHODS:
      Sixty patients affected by functional gastrointestinal disorders (11 functional
      bloating, 36 constipation-predominant, and 13 diarrhea-predominant irritable
      bowel syndrome) and moderate to severe bloating took part in the study. Twenty
      sex- and age-matched healthy volunteers were enrolled as a control group. All the
      subjects underwent a preliminary evaluation of breath hydrogen excretion after
      oral lactulose. Then, on a separate day, an evaluation of sensitivity thresholds
      at rectal level was performed with a barostat before and after the induction of
      colonic fermentation with oral lactulose. A control test with electrolyte
      solution was also performed. RESULTS: Both breath hydrogen excretion and mouth-to
      cecum transit time did not differ between the 4 groups studied. Neither
      electrolyte solution nor lactulose modified sensitivity thresholds in healthy
      volunteers. In low hydrogen producers, basal perception and discomfort thresholds
      were similar to high hydrogen producers, but after lactulose both perception and
      discomfort thresholds were significantly reduced only in low hydrogen producers.
      CONCLUSIONS: A subgroup of patients with functional gastrointestinal disorders
      and moderate to severe bloating might have hypersensitivity to products of
      colonic fermentation.

PMID- 16979387
TI  - Clinical trial optimization: Monte Carlo simulation Markov model for planning
      clinical trials recruitment.
AB  - INTRODUCTION: The patient recruitment process of clinical trials is an essential
      element which needs to be designed properly. METHODS: In this paper we describe
      different simulation models under continuous and discrete time assumptions for
      the design of recruitment in clinical trials. RESULTS: The results of
      hypothetical examples of clinical trial recruitments are presented. The
      recruitment time is calculated and the number of recruited patients is quantified
      for a given time and probability of recruitment. The expected delay and the
      effective recruitment durations are estimated using both continuous and discrete
      time modeling. CONCLUSION: The proposed type of Monte Carlo simulation Markov
      models will enable optimization of the recruitment process and the estimation and
      the calibration of its parameters to aid the proposed clinical trials. A
      continuous time simulation may minimize the duration of the recruitment and,
      consequently, the total duration of the trial.

PMID- 16979389
TI  - Rev1 enhances CAG.CTG repeat stability in Saccharomyces cerevisiae.
AB  - Trinucleotide repeats (TNRs) frequently expand in certain human genetic diseases,
      often with devastating pathological consequences. TNR expansions require the
      addition of new DNA; accordingly, molecular models suggest aberrant DNA
      replication or error-prone repair synthesis as the sources of most instability.
      Some proteins are currently known that either promote or inhibit TNR mutability.
      To identify additional proteins that help protect cells against TNR instability,
      yeast mutants were isolated with higher than normal rates of CAG.CTG tract
      expansions. Surprisingly, a rev1 mutant was isolated. In contrast to its
      canonical function in supporting mutagenesis, we found that Rev1 reduces rates of
      CAG.CTG repeat expansions and contractions, as judged by the behavior of the rev1
      mutant. The rev1 mutator phenotype was specific for TNRs with hairpin forming
      capacity. Mutations in REV3 or REV7, encoding the subunits of DNA polymerase zeta
      (pol zeta), did not affect expansion rates in REV1 or rev1 strains. A rev1 point
      mutant lacking dCMP transferase activity was normal for TNR instability, whereas
      the rev1-1 allele that interferes with BRCT domain function was as defective as a
      rev1 null mutant. In summary, these results indicate that yeast Rev1 reduces
      mutability of CAG.CTG tracts in a manner dependent on BRCT domain function but
      independent of dCMP transferase activity and of pol zeta.

PMID- 16979390
TI  - Determination of salivary dehydroepiandrosterone using liquid chromatography-
      tandem mass spectrometry combined with charged derivatization.
AB  - A sensitive liquid chromatography-electrospray ionization-tandem mass
      spectrometric (LC-ESI-MS-MS) method for the quantification of
      dehydroepiandrosterone (DHEA) in human saliva has been developed and validated.
      The saliva was deproteinized with acetonitrile, purified using a Strata-X
      cartridge, derivatized with the permanently charged reagent, 2-hydrazino-1
      methylpyridine (HMP), and subjected to LC-MS-MS. The derivatization with HMP was
      very effective for increasing the detectability of DHEA in the positive-ESI-MS.
      Quantification was based on the selected reaction monitoring and androsterone was
      used as an internal standard. This method allowed the reproducible and accurate
      quantification of the salivary DHEA using a 200-microl sample and the limit of
      quantitation for DHEA was 25 pg/ml. No significant matrix effect or change in the
      measured value by freeze/thaw repetition was observed. The developed method was
      applied to clinical studies, and produced satisfactory results.

PMID- 16979388
TI  - DNA polymerase beta null mouse embryonic fibroblasts harbor a homozygous null
      mutation in DNA polymerase iota.

PMID- 16979391
TI  - Determination of the dopamine agonist rotigotine in microdialysates from the rat
      brain by microbore column liquid chromatography with electrochemical detection.
AB  - Rotigotine, an investigational dopamine agonist formulated as a patch, is being
      studied in Parkinson's disease. A microdialysis technique, in combination with
      microbore column liquid chromatography and electrochemical detection, was
      developed to monitor rotigotine levels in the brain. Microdialysis probes were
      inserted into the striata of anesthetized rats, and samples were collected during
      perfusion with Ringer's solution. Rotigotine was separated using a C18 reversed
      phase column. The mobile phase consisted of 50mM Na(2)HPO(4) x 2H(2)O, 2.5 mM
      sodium octyl sulfonate, and pH 4.5; 35% volume to volume acetonitrile. The flow
      rate was 30 microl/min, and the potential of the glassy carbon electrode was set
      to +850 mV. The method allowed monitoring of the time course of brain
      extracellular rotigotine levels with a detection limit of 1 nM following either
      intravenous (0.5 mg/kg) or subcutaneous (5.0 mg/kg) rotigotine injection.

PMID- 16979392
TI  - Neuroactive hormones and interpersonal trust: international evidence.
AB  - Social attachment is vital for human health and welfare. Recent experimental
      evidence in humans has identified the role of neuroactive hormones, especially
      the peptide oxytocin, in mediating trusting behaviors. Herein, we test if the
      endocrinological basis for trust between humans scales up to the country level.
      Trust pervades nearly every aspect of our daily lives, yet survey data on trust
      show substantial variation across countries. Using 31 measures of biological,
      social, and environmental factors associated with hormone levels for a sample of
      41 countries, we find that two classes of factors are related to trust:
      consumption of plant-based estrogens (phytoestrogens), and the presence of
      environmental conditions that include measures of estrogen-like molecules. Our
      findings provide preliminary evidence that interpersonal trust at the country
      level may be related to the intake of neuroactive hormones.

PMID- 16979393
TI  - Novel highly biodegradable biphasic tricalcium phosphates composed of alpha
      tricalcium phosphate and beta-tricalcium phosphate.
AB  - Novel biodegradable biphasic tricalcium phosphates (BTCP) composed of alpha
      tricalcium phosphate (alpha-TCP) and beta-tricalcium phosphate (beta-TCP) were
      successfully synthesized by heating amorphous calcium phosphate precursors with
      different structures at 800 degrees C for 3 h. The ratio of alpha-TCP and beta
      TCP in the calcium phosphate particle can be controlled by aging time and pH
      value during synthesis of the amorphous precursor.

PMID- 16979394
TI  - Magnetoencephalography of the newborn brain.
AB  - This paper reviews the use of event-related magnetic fields (ERFs) in infants;
      ERFs can be derived from magnetoencephalography by means of averaging. Basic
      perceptive skills are important prerequisites for the infant's later development.
      The automatic cortical processes related to processing auditory, somatosensory
      and visual stimuli can be addressed by using responses recorded directly from the
      brain. The traditional method, the event-related potential (ERP), has recently
      been accompanied by ERFs. Similarly to ERPs, higher processes related to short
      term memory, stimulus comparisons, and attention allocation can also be studied
      with ERFs. Further, since addressing the neonatal higher cognitive and social
      capabilities is challenging using only behavioural means, ERFs provide
      information on these important functions at a very early stage immediately after
      birth or in some cases even before birth. The main advantage of ERFs, compared to
      ERPs, is detection of the signals with high accuracy both with respect to the
      noise level and estimation of the spatial location.

PMID- 16979395
TI  - Serum OPG and RANKL levels before and after intravenous bisphosphonate treatment
      in Paget's disease of bone.
AB  - Paget's disease of bone (PDB) is a focal disorder of bone remodeling
      characterized by increased osteoclast-mediated bone resorption. Even though
      increasing evidence indicates enhanced nuclear factor-kB (NF-kB) signaling as a
      common mechanism involved in PDB and other related disorders, few studies
      investigated circulating osteoprotegerin (OPG) and receptor of activator of NF-kB
      ligand (RANKL) levels in PDB patients. In this study we explored the
      relationships between OPG or RANKL levels and bone turnover markers in a group of
      patients with PDB, before and after intravenous bisphosphonate treatment
      (pamidronate 60 mg). Both OPG and RANKL were markedly elevated in PDB patients
      with respect to control groups (healthy or osteoporotic postmenopausal women and
      elderly men) and were positively associated with bone turnover markers. Higher
      levels of these cytokines were observed in polyostotic than monostotic PDB cases.
      The ratio between RANKL and OPG was more than 3-fold higher in PDB patients than
      in controls. Interestingly, in the group of patients treated with pamidronate, we
      found an increase in OPG levels that become statistically significant after 3 and
      6 months from treatment. A trend toward a decrease in RANKL levels after
      treatment was also observed. The RANKL/OPG ratio was significantly reduced after
      3 and 6 months of therapy. In contrast, in patients classified as non-responders,
      OPG and RANKL levels after pamidronate infusion did not significantly differ with
      respect to pre-treatment values. Thus, the positive effect of amino
      bisphosphonates in the treatment of PDB may be due to either direct or indirect
      suppression of RANKL-induced bone resorption through decreased RANKL and
      increased OPG production.

PMID- 16979396
TI  - Adipokines and treatment with niacin.
AB  - Adipokines may serve as an important etiologic link between atherosclerosis and
      obesity. Because adipose tissue is one site of action of the lipid-lowering drug
      niacin, we investigated whether niacin treatment would affect not only lipids but
      also adipokines. Twenty-four patients were treated with extended-release niacin.
      During the first 4 weeks the daily dose was increased at weekly intervals from
      375 to 1000 mg, which was maintained for 4 weeks. Thereafter, the dose was 1500
      mg for another 6 weeks. Adiponectin increased by 54% and 94%, respectively,
      resistin was lowered only moderately, and leptin not at all. Because adiponectin
      has repeatedly been shown to be negatively associated with atherosclerotic risk,
      its pronounced increase may bring about additional atheroprotection by niacin
      beyond its improvement in lipids.

PMID- 16979397
TI  - Protective effect of brain-derived neurotrophic factor on pancreatic islets in
      obese diabetic mice.
AB  - We have previously demonstrated that brain-derived neurotrophic factor (BDNF)
      ameliorates glucose metabolism and energy expenditure in obese diabetic db/db
      mice. In the present study, the effect of BDNF treatment on pancreatic islets of
      db/db mice was examined, using vehicle-treated pair-fed db/db mice as controls.
      Brain-derived neurotrophic factor (10 mg/kg) or vehicle was subcutaneously
      administered to male db/db mice for 4 weeks. The food intake of vehicle-treated
      db/db mice was restricted and precisely synchronized with that of BDNF-treated
      db/db mice using a pellet pair-feeding apparatus because BDNF decreases food
      intake in hyperphagic mice. Repetitive administration of BDNF significantly
      lowered the blood glucose concentration compared with pair-fed vehicle-treated
      db/db mice. The pancreatic insulin and glucagon concentrations were measured in
      db/db mice to evaluate the effect of BDNF on the pancreas. Although the insulin
      concentration in the pancreas of pair-fed vehicle-treated db/db mice was lower
      than in nondiabetic control +m/+m mice, it was higher in BDNF-treated db/db mice
      than in vehicle-treated pair-fed db/db mice and comparable to the concentration
      in +m/+m mice. The glucagon concentration in the pancreas of vehicle-treated pair
      fed db/db mice was higher than in +m/+m mice, and BDNF partially decreased the
      glucagon concentration in the pancreas of db/db mice compared with vehicle.
      Histologic analyses of pancreatic sections were performed to characterize the
      mechanism through which BDNF modulates the hormonal concentration in the pancreas
      of db/db mice. Although there were no significant differences in the number and
      total area of islets between the BDNF- and vehicle-treated groups, immunostaining
      with an anti-insulin antibody indicated that the islet beta-cell area in BDNF
      treated db/db mice was larger than that in vehicle-treated pair-fed db/db mice.
      Furthermore, immunostaining with an antiglucagon antibody indicated that BDNF
      normalized the delocalization of non-beta cells in islets of db/db mice. Electron
      microscopic images of beta cells indicated a decrease in secretory granules in
      vehicle-treated pair-fed db/db mice; this change was reversed in BDNF-treated
      db/db mice and reached a level comparable to that found in +m/+m mice. These
      findings suggest that BDNF prevents exhaustion of the pancreas in diabetic mice
      by maintaining the histologic cellular organization of beta cells and non-beta
      cells in pancreatic islets and restoring the level of insulin-secreting granules
      in beta cells.

PMID- 16979398
TI  - Elevated serum uric acid levels in metabolic syndrome: an active component or an
      innocent bystander?
AB  - Elevated serum uric acid (SUA) levels are commonly seen in patients with the
      metabolic syndrome (MetS). Several mechanisms, both direct and indirect, connect
      the increased SUA levels with the established diagnostic criteria of MetS. It is
      possible that the increased cardiovascular disease risk associated with the MetS
      is partially attributed to elevated circulating SUA concentration. Several drugs
      used in the treatment of MetS may alter SUA levels. Thus, lifestyle measures
      together with the judicious selection of drugs for the treatment of hypertension,
      dyslipidemia, and insulin resistance associated with MetS may result in a
      reduction of SUA levels and possibly cardiovascular disease risk. This review
      summarizes the pathophysiologic association between SUA and MetS and focuses on
      the prevention of hyperuricemia and its cardiovascular consequences.

PMID- 16979399
TI  - Effect of weight loss resulting from a combined low-fat diet/exercise regimen on
      low-density lipoprotein particle size and distribution in obese women.
AB  - Weight loss resulting from diet interventions has been shown to favorably affect
      low-density lipoprotein (LDL) particle size and distribution, and, hence,
      decrease cardiovascular disease risk. However, the effect of a dietary weight
      loss strategy when combined with exercise, on LDL electrophoretic
      characteristics, has yet to be tested. This study examined the effect of a weight
      loss intervention that combined a low-fat diet with moderate endurance training,
      on LDL particle size and distribution in obese women. Thirty obese,
      hypercholesterolemic women participated in a controlled longitudinal weight loss
      trial, which consisted of (1) a 2-week pre-stabilization phase, (2) a 20-week
      weight loss phase, and (3) a 2-week post-stabilization phase. Weight reduction
      resulted from a low-fat diet (<30% fat, 50%-60% carbohydrate, 20% protein)
      combined with an endurance training program (>40 minutes moderate training, 3
      times per week). Mean weight loss was 14.8% (P < .01) of initial body weight.
      Total, LDL cholesterol, and triacylglycerol concentrations decreased (P < .01) by
      8.9%, 7.5%, and 27.1%, respectively, whereas high-density lipoprotein cholesterol
      concentrations increased (P < .01) by 9.9%. No significant differences were noted
      for LDL peak or integrated particle size. The relative proportion of small,
      medium, and large particles was not significantly different posttreatment.
      Estimated cholesterol concentrations in large- and medium-sized LDL particles
      decreased (P < .05) by 15.3% and 5.9%, respectively, as a result of weight loss.
      No effect was noted for estimated cholesterol concentrations in small size LDL
      particles. In conclusion, these findings suggest that weight loss, resulting from
      a low-fat diet/exercise program, has only a minimal effect on LDL particle size
      and distribution.

PMID- 16979400
TI  - Low-density lipoproteins generated during an oral fat load in mild
      hypertriglyceridemic and healthy subjects are smaller, denser, and have an
      increased low-density lipoprotein receptor binding affinity.
AB  - Triglyceride-rich lipoproteins generated during the postprandial phase are
      atherogenic. Large very low-density lipoproteins (LDLs) or chylomicrons (CMs) are
      not as atherogenic as their remnants (Rem). Small and dense LDLs are associated
      with cardiovascular disease. Low-density lipoprotein size is partly under genetic
      control and is considered as a relatively stable LDL feature. In this article, we
      present data on retinyl palmitate kinetics correlated with the modification of
      LDL features in terms of size, density, and in vitro receptor binding affinity
      after an oral fat load. Six nondiabetic, hypertriglyceridemic (HTG) patients and
      6 healthy controls were examined. Low-density lipoprotein size was assessed by
      gradient gel electrophoresis, and LDL density by density gradient
      ultracentrifugation. Low-density lipoprotein binding affinity was tested by in
      vitro competition binding assay on normal human skin fibroblasts (HSFs) and
      hepatoma cells (HepG2). Kinetic parameters were estimated in CM and Rem fractions
      by compartmental modeling. Hypertriglyceridemic patients showed significantly
      higher triglyceride area and a slower CM fractional catabolic rate. Postprandial
      LDL density increased both in HTG patients and in the control group with a
      significant difference between groups at 6 hours. Fasting LDL size was lower in
      HTG patients vs controls but decreased similarly in the postprandial phase. Low
      density lipoprotein size and density postprandial modifications were not
      correlated with any investigated parameter. Postprandial LDLs were internalized
      more efficiently by HSF than baseline LDL only in the HTG group. In conclusion,
      postprandial LDLs are smaller and denser compared with fasting LDLs after an oral
      fat load. Postprandial LDLs also slightly increased their affinity to the HSF
      cell receptors.

PMID- 16979401
TI  - Physiologic concentrations of leptin increase collagen production by non
      immortalized human hepatic stellate cells.
AB  - The effects of leptin, in concentrations seen in obesity, on collagen production
      and turnover in non-immortalized human hepatic stellate cell (HSC), were unknown.
      The profibrogenic effects of leptin in these cells were studied. Hepatic stellate
      cells were obtained from resected livers. Collagen I/III gene expression and
      protein production were measured by quantitative real-time polymerase chain
      reaction and sodium dodecyl sulfate-polyacrylamide gel electrophoresis,
      respectively. The signal transduction pathways involved were evaluated by
      specific blockers of the phosphatidylinositol 3-kinase (PI3K), mitogen-activated
      protein kinase kinase (MEK), and Janus kinase 2 (JAK2). The effects on matrix
      metalloproteinase 1 (MMP-1) and tissue inhibitor of metalloproteinase 1 (TIMP-1)
      were assessed by their gene transcript levels, collagenolytic activity of cell
      culture supernatants, and MMP-1 protein levels. At concentrations seen in
      nonobese individuals ([leptin] < 10 ng/mL), leptin did not affect collagen
      production. At concentrations seen in obesity (30-50 ng/mL), leptin increased
      collagen I and III messenger RNA (mRNA) transcript levels by 286% +/- 55% (P <
      .001) and 167% +/- 62% (P < .007) and protein production by 45.8% +/- .02% and
      84.39% +/- .01%, respectively. These effects were blocked by JAK2 inhibition as
      well as PI3K inhibition. Although MEK inhibition blocked leptin-induced
      procollagen I and III mRNA levels, there were no significant effects on collagen
      I and III protein levels. Leptin (10-50 ng/mL) had no significant effects on MMP
      1 or TIMP-1 mRNA levels, collagenolytic activity, or MMP-1 protein levels. In
      conclusion, leptin, at levels seen in obese individuals, produces an increase in
      collagen production by HSC acting through the JAK and PI3K pathways. At these
      concentrations, leptin does not affect MMP-1 or TIMP-1 expression or
      collagenolytic activity of HSC.

PMID- 16979402
TI  - Utility of elevated 2-hour postload plasma glucose as an alternative to elevated
      fasting glucose as a criterion for the metabolic syndrome.
AB  - We hypothesize that many persons with postchallenge hyperglycemia (PCH) but who
      do not meet the National Cholesterol Education Program (NCEP) criteria
      characterize a phenotype that is similar to the metabolic syndrome (MS) traits.
      Subjects included 725 Japanese who underwent a 75-g oral glucose tolerance test.
      If 2-hour plasma glucose of 7.8 mmol/L or higher was present, subjects with
      fasting glucose of less than 6.1 mmol/L could have one component of the MS (PCH
      MS). Data obtained by the 75-g oral glucose tolerance test were used to calculate
      3 insulin sensitivity indexes according to formulas proposed by Matsuda and
      DeFronzo (insulin sensitivity index composite), Stumvoll et al (Srumvoll index),
      and Mari et al (oral glucose insulin sensitivity index). Based on the PCH-MS and
      NCEP-MS criteria, 395 had neither PCH-MS nor NCEP-MS, 85 had PCH-MS, and 245 had
      NCEP-MS. Subjects with PCH-MS exhibited higher systolic blood pressure and
      triglyceride levels, lower high-density lipoprotein cholesterol levels, and lower
      insulin sensitivity than those who had neither PCH-MS nor NCEP-MS. A similar
      profile was observed when subjects with NCEP-MS were compared with those who had
      neither PCH-MS nor NCEP-MS. All 3 indexes of insulin sensitivity were
      significantly lower in subjects with PCH-MS than in those who had neither PCH-MS
      nor NCEP-MS, and approximately 66% of PCH-MS was in an insulin-resistant state.
      On the other hand, there was no statistical difference in the values between PCH
      MS and NCEP-MS. Our data support the addition of abnormal 2-hour plasma glucose
      as a criterion for the MS, when fasting glucose is normal.

PMID- 16979403
TI  - Body composition and metabolic effects of a diet and exercise weight loss regimen
      on obese, HIV-infected women.
AB  - HIV has classically been a wasting disease. However, in the United States,
      obesity is increasingly common among HIV-infected individuals receiving effective
      antiviral treatment. The risks of obesity are unclear in HIV, although the
      increased prevalence of diabetes and cardiovascular disease in the presence or
      absence of obesity causes growing concern. This study aimed to assess the effects
      of weight loss (through energy restriction combined with aerobic and resistance
      exercise) on body composition, body fat distribution, resting energy expenditure,
      quality of life (QOL), strength and fitness, and metabolic risk factors in obese,
      HIV-infected women. Eighteen HIV-infected women with a body mass index of 30 or
      more completed a 12-week weight loss program. Before and after the intervention,
      body composition and fat distribution by dual energy x-ray absorptiometry and
      whole-body magnetic resonance imaging, resting energy expenditure by indirect
      calorimetry, QOL, strength, and fitness were measured. Insulin sensitivity by
      intravenous glucose tolerance test and circulating cardiovascular risk factors
      (including lipids, tissue plasminogen activator, and plasminogen activator
      inhibitor 1) were measured in a subset (n = 9). Daily food intake and total body
      weight decreased (mean +/- SD) by 3195 +/- 477 kJ and 6.7 +/- 4.2 kg,
      respectively. Weight lost was 95.5% fat by dual energy x-ray absorptiometry or
      6.2 L of subcutaneous adipose tissue, 0.7 L visceral adipose tissue, and 0.8 L
      skeletal muscle by magnetic resonance imaging. Resting energy expenditure fell
      approximately 419 kJ, strength and fitness increased by 28.9% +/- 18.5% and 36.8%
      +/- 41.6%, respectively, and QOL improved in 11 of 13 dimensions. There was
      significant insulin resistance in the subset with metabolic measurements at
      baseline, and at follow-up there was no improvement in fasting glucose, insulin,
      or insulin sensitivity, nor was there any change in fasting lipids, tissue
      plasminogen activator, or plasminogen activator inhibitor 1. There was no
      significant change in CD4 count or HIV viral load. In conclusion, moderate weight
      loss achieved by a short-term program of diet and exercise in obese HIV-positive
      women appears safe and induces loss of adiposity in both the subcutaneous adipose
      tissue and visceral adipose tissue regions. Despite reduced food intake, weight
      and fat loss, as well as improvements in strength, fitness, and QOL, the lack of
      improvement in metabolic parameters suggests that additional interventions may be
      necessary to reduce the risk of diabetes and cardiovascular disease in this
      population.

PMID- 16979404
TI  - Computed tomography scans of intra-abdominal fat, anthropometric measurements,
      and 3 nonobese metabolic risk factors.
AB  - The present cross-sectional study of 46 adult Danish white men and women aimed to
      evaluate association between intra-abdominal obesity, 4 anthropometric
      measurements of obesity, and combinations of 3 nonobese metabolic risk factors:
      systolic blood pressure of 130 mm Hg or higher, serum triglyceride concentration
      of more than 1.7 mmol/L, and fasting capillary blood glucose concentration of 5.6
      mmol/L or more. For 80% of the subjects, intra-abdominal fat on a computed
      tomography scan of the abdomen using a cutoff limit of more than 144 cm(2) gave a
      correct classification of combinations of at least 2 of the 3 metabolic risk
      factors. Body mass index and waist circumference were better markers of intra
      abdominal obesity than waist-to-hip ratio in receiver operating characteristic
      analyses (P = .0035). Body mass index of more than 26 kg/m(2) and waist
      circumference of more than 0.92 m classified 76% and 74% of the subjects
      correctly regarding combinations of the 3 nonobese metabolic risk factors. Intra
      abdominal obesity was significantly stronger associated with the combinations
      than a raised waist-to-hip ratio (P = .016). Both body mass index and waist
      circumference may be used as markers of intra-abdominal obesity, whereas waist-to
      hip ratio was significantly inferior. Correspondingly, both body mass index and
      waist circumference were better than waist-to-hip ratio to indicate combinations
      of the 3 nonobese metabolic risk factors.

PMID- 16979405
TI  - The differential effects of age on the association of KLOTHO gene polymorphisms
      with coronary artery disease.
AB  - The Klotho knockout mouse is thought to be a good animal model for human aging.
      Recent studies have reported on the association of KLOTHO gene mutation with
      cardiovascular disease in humans. We observed the frequencies of single
      nucleotide polymorphisms, that is, G-395A in the promoter region, C1818T in exon
      4, and a functional variant, KL-VS, of KLOTHO gene in Koreans, and we
      investigated their relationships with the presence of coronary artery disease
      (CAD) in patients who had undergone coronary angiograms. A total of 274 subjects
      who underwent coronary angiograms because of chest pain were enrolled, and their
      blood pressure, body mass index, fasting blood glucose level, and lipid profiles
      were measured. Genotypings were performed on samples of their blood with real
      time polymerase chain reaction. Two single nucleotide polymorphisms, G-395A and
      C1818T, complied with Hardy-Weinberg equilibrium. For the KL-VS genotype, 1
      homozygote subject for the adverse allele was detected among the entire
      population (GG for F352V and CC for C370S). When the subjects were classified
      into 4 groups according to the number of stenotic vessels, there were no
      differences among the mean values of the cardiovascular risk factors, except for
      age and the fasting blood glucose levels, which showed a significant difference
      between that of the normal and the diseased vessel groups. There were no
      differences in the prevalence of CAD according to the genotypes of the G-395A
      polymorphism; however, for the C1818T polymorphism, those subjects with the T
      allele showed a lower prevalence of CAD than those with the CC genotype. When the
      subjects were divided into 2 groups according to age, in the group younger than
      60 years, T allele carriers of the C1818T polymorphism showed a lower prevalence
      of CAD than did the noncarriers. In the group older than 60 years, A allele
      carriers of the G-395A polymorphism showed a lower prevalence of CAD than did the
      noncarriers. On the haplotype analysis, the GG-CC haplotype showed an increased
      risk for CAD with an odds ratio of 2.594 (95% confidence interval, 1.385-4.858; P
      = 0.003). Differential effects of age were observed in the association of KLOTHO
      G-395A and C1818T polymorphisms with CAD in Koreans. The KL-VS variant seems to
      be rarely found in the Korean population. These results infer the possibility of
      the KLOTHO gene being a candidate gene of atherosclerosis in humans, and further
      research on this topic needs to be done.

PMID- 16979406
TI  - Physiologic roles of 11beta-hydroxysteroid dehydrogenase type 2 in kidney.
AB  - We developed enzyme-linked immunosorbent assays to measure urinary free cortisone
      (E) and cortisol (F) and analyzed correlations between clinical measures
      reflecting mineralocorticoid action and 24-hour urinary excretion of E and F or
      their ratio, uE/F, which has been considered as the most sensitive index of renal
      11beta-hydroxysteroid dehydrogenase type 2 activity. Two hundred nineteen healthy
      men were enrolled in this study. The uE/F ratio was 1.10 +/- 0.41 (mean +/- SD),
      and a strong linear correlation between uE and uF was observed in a double
      reciprocal plot. Urinary acid-labile aldosterone excretion had a negative
      correlation with 24-hour urinary Na excretion and Na/K ratio, but uE/F ratio had
      a weak positive correlation with the Na/K ratio and no significant correlation
      with 24-hour urinary Na excretion. In contrast, uE and uF had positive
      correlations with 24-hour urinary excretions of Na and K, raising the possibility
      of separate renal effects mediated by the glucocorticoid receptor. Furthermore,
      uE and uE/F ratio had strong negative correlations with urinary concentrations of
      Na and K. These results suggest that renal 11beta-hydroxysteroid dehydrogenase
      type 2 is an important regulatory factor of renal Na and K handlings
      independently of and/or complementary to the mineralocorticoid action of
      aldosterone.

PMID- 16979407
TI  - Effects of exercise training on resting metabolic rate in postmenopausal African
      American and Caucasian women.
AB  - Ambiguous findings have been reported in previous studies concerning the
      relationships between resting metabolic rate (RMR), effects of exercise, and race
      in postmenopausal women. The purposes of this study were (1) to determine the
      effect of exercise training on RMR in postmenopausal women and (2) to determine
      whether this effect is different by race. We analyzed data from 24 African
      American (AA) (age, 56.3 +/- 5.0 years) and 23 Caucasian (CA) (age, 58.6 +/- 6.1
      years) women. RMR was measured by indirect calorimetry after an overnight fast.
      Subjects completed tests of maximal exercise with metabolic measurements, waist
      to hip ratio, and body composition. At the completion of all tests, each subject
      was randomly assigned to either the exercise training or the control group.
      Aerobic exercise was performed 3 to 4 days per week for 6 months. Intensity was
      set at 70% to 85% maximal heart rate for 45 to 60 minutes per session. Both AA
      and CA exercise groups had a significant decrease (P < .05) in body weight
      (kilograms), percent body fat, and body mass index (BMI) and an increase in
      aerobic capacity, whereas the control groups did not change. There were no race
      effects. AA women exhibited significantly lower values than CA women for measured
      RMR (P < .05). The RMR (kilojoules) of the AA women (both control and exercise
      groups) decreased over time (P < .05), whereas the RMR of the CA women did not
      change. Adjusting RMR for BMI or for changes in lean body mass and fat mass did
      not alter these results. In conclusion, this 6-month endurance-training program
      did not affect RMR in these postmenopausal women, as RMR did not change in CA
      women, but decreased significantly over time in both groups of AA women. The
      factors that contribute to these findings should be the focus of future studies.

PMID- 16979408
TI  - Differential effects of n-3 polyunsaturated fatty acids on metabolic control and
      vascular reactivity in the type 2 diabetic ob/ob mouse.
AB  - Diets rich in monounsaturated fatty acids (MUFA) are recommended for individuals
      with type 2 diabetes mellitus (T2DM). The American Heart Association recommends
      increasing intakes of n-3 polyunsaturated fatty acids (PUFA) to reduce the risk
      of vascular disease in high-risk individuals; however, the long-term effects of
      these bioactive fatty acids on glucose metabolism in insulin resistance are
      controversial. The present studies were conducted to evaluate the effects of
      diets rich in both MUFA and alpha linolenic acid (C18:3n-3, ALA),
      eicosapentaenoic acid (C20:5n-3, EPA), or docosahexaenoic acid (C22:6n-3, DHA),
      on glycemic control and other parameters related to vascular health in a mouse
      model of T2DM and insulin resistance. Male ob/ob mice (n = 15 per treatment) were
      fed 1 of 4 lipid-modified formula diets (LFDs) for 4 weeks: (1) MUFA control, (2)
      ALA blend, (3) EPA blend, and (4) DHA blend. A portion of a MUFA-rich lipid blend
      in the control LFD was replaced with 11% to 14% energy as n-3 PUFA. After 4
      weeks, plasma glucose response to a standard meal (1.5 g carbohydrate/kg body
      weight) and insulin challenge (2 U/kg body weight, IP) was assessed, and samples
      were collected for analysis of glucose, insulin, and lipids. Vascular reactivity
      of isolated aortic rings was assessed in an identical follow-up study. The
      results showed that insulin-resistant mice fed an LFD with EPA and/or DHA blends
      had significantly (P < .05) lower triglycerides and free fatty acids, but insulin
      sensitivity and fasting plasma glucose were not improved. However, mice fed with
      the ALA blend had significantly improved insulin sensitivity when compared to
      those fed with other LFD (P < .05). Animals fed an LFD with n-3 PUFA from marine
      or plant sources showed significantly improved vascular responses as compared
      with the MUFA-rich LFD (E(max), P < .05) and ob/ob reference mice consuming chow
      (E(max) and pEC(50), P < .05). In summary, long-term consumption of LFD with n-3
      PUFAs improved blood lipids and vascular function in an animal model of insulin
      resistance and T2DM; however, only MUFA-rich LFD with ALA also improved both
      insulin sensitivity and glycemic responses. Further studies of MUFA-rich LFD with
      ALA with individuals who have T2DM are warranted.

PMID- 16979409
TI  - Effect of aerobic training on plasma levels and subcutaneous abdominal adipose
      tissue gene expression of adiponectin, leptin, interleukin 6, and tumor necrosis
      factor alpha in obese women.
AB  - Adipocytokines secreted by adipose tissue are suggested to play a role in the
      development of obesity-related complications. Regular aerobic exercise has been
      shown to reduce the risk of metabolic complications in obese subjects. The aim of
      this study was to investigate the effect of aerobic training on gene expression
      in subcutaneous abdominal adipose tissue (SCAAT) and on plasma levels of several
      adipocytokines in obese women. Twenty-five obese sedentary premenopausal women
      (body mass index, 32.18 +/- 3.17 kg/m(2)) underwent a 12-week aerobic exercise
      program, with a frequency of 5 d/wk and intensity corresponding to 50% of
      individual maximal oxygen consumption (V(.-)(O(2)max)) consisting of 2 sessions
      per week of supervised aerobic exercise and 3 sessions per week of home-based
      exercise on a bicycle ergometer. Before and after the aerobic training, (V(.
      )(O(2)max)) and body composition were measured and plasma and SCAAT biopsy
      samples (in a subgroup of 8 subjects) were obtained for determination of plasma
      and messenger RNA levels of adipocytokines (leptin, adiponectin, interleukin 6,
      tumor necrosis factor alpha). The aerobic training resulted in an increase of
      subjects' V o(2)max by 12.8% (24.6 +/- 3.9 vs 27.7 +/- 4.8 mL x min(-1) x kg(-1),
      P < .05). Body weight and fat mass were reduced by 5.9% (88.5 +/- 8.2 vs 83.3 +/-
      7.7 kg, P < .001) and 6.4% (38.8 +/- 4.2% vs 36.3 +/- 4.6%, P < .001),
      respectively, and the revised QUantitative Insulin sensitivity ChecK Index
      (QUICKI) increased (0.43 +/- 0.06 vs 0.48 +/- 0.06, P < .05) during the aerobic
      training. No aerobic training-induced changes in messenger RNA levels of the
      investigated genes in SCAAT were observed. A decrease of plasma leptin (24.3 +/-
      8.7 vs 18.1 +/- 8.3 ng/mL, P < .05) was detected, whereas plasma levels of other
      cytokines remained unchanged. In moderately obese females, 3 months' aerobic
      training did not promote changes in the adipose tissue gene expression or plasma
      levels of the adipocytokines (except for leptin) involved in a regulation of
      lipid and carbohydrate metabolism.

PMID- 16979410
TI  - Efficacy of a pedometer-based physical activity program on parameters of diabetes
      control in type 2 diabetes mellitus.
AB  - The aim of the study was to determine whether a recommendation to walk 10000
      steps per day would result in significant improvements in glycemic control,
      insulin sensitivity, and cardiovascular risk in patients with type 2 diabetes
      mellitus. The study was a 6-week randomized controlled trial that included 30
      patients with type 2 diabetes mellitus. After 10 days of baseline activity,
      patients were randomized into 2 groups: control and active. The control group (n
      = 15) was instructed to continue with their baseline activity for 6 weeks. The
      active group (n = 15) was instructed to walk at least 10000 steps per day 5 or
      more days per week, for 6 weeks. Data relevant to glycemic control and other
      parameters of health were collected at study weeks 0 and 6. There were no
      differences in the baseline activity between groups (P = .36). Subjects in the
      active group significantly increased physical activity by 69% during the
      intervention phase of the study (P = .002), whereas there was no change in the
      physical activity of the control group (P > .05). High-density lipoprotein
      cholesterol and resting energy expenditure significantly increased in the active
      group (P < .05). Finally, plasminogen activator inhibitor 1 (PAI-1) activity was
      reduced by exercise relative to the control group (P = .03). There were no
      differences in any other study parameters during the 6-week study. In conclusion,
      short-term intervention with a pedometer increased physical activity and
      positively affected plasminogen activator inhibitor 1 activity in previously
      inactive patients with type 2 diabetes mellitus. The use of a pedometer may prove
      to be an effective tool for promoting healthy lifestyle changes that include
      daily physical activity and self-monitoring of therapeutic goals.

PMID- 16979411
TI  - Metabolic characteristics of soleus muscle in relation to insulin action in the
      offspring of hypertensive parents.
AB  - Insulin resistance affecting skeletal muscle metabolism is present in the
      prehypertensive state. The aim of our study was to test the hypothesis that blood
      pressure value is related to skeletal muscle composition, measured by (31)P
      magnetic resonance (MR) spectroscopy, and to insulin sensitivity in the offspring
      of hypertensive parents (OH) and healthy controls. Study groups consisted of 10
      healthy young lean OH with normal glucose tolerance, confirmed with oral glucose
      tolerance test, and 13 controls matched for age, sex, and body mass index.
      Insulin action was estimated as glucose disposal (M), glucose metabolic clearance
      rate (MCR), and insulin sensitivity index (M/I) during a 10-hour hyperinsulinemic
      euglycemic clamp. The sum of immunoreactive insulin values from the oral glucose
      tolerance test was calculated. (31)P MR spectroscopy was performed on a whole
      body MR scanner (Siemens Vision, Erlangen, Germany) operating at 1.5 T and
      equipped with actively shielded gradient coils. There were no differences in
      common metabolic and anthropometric parameters between OH and controls except for
      the blood pressure, which was in the range of normal to high-normal level in OH.
      Mean blood pressure was significantly higher in OH (95.73 +/- 4.39 vs 83.76 +/-
      3.95 mm Hg; P < .001). Trend toward insulin resistance was registered in OH with
      significantly lower M/I (0.74 +/- 0.47 vs 1.42 +/- 0.65 mg x kg(-1) x min(-1) x
      mIU(-1) x L(-1); P < .05). There were no significant differences in total serum
      magnesium (sMg) levels between OH and controls, although a positive correlation
      exists between sMg and insulin sensitivity expressed as M (r = 0.63, P < .01),
      MCR (r = 0.54, P < .01), and M/I (r = 0.51, P < .05). No differences in signal
      intensities of phosphocreatine (PCr), phosphomonoesters, phosphodiesters,
      inorganic phosphates (Pi), adenosine triphosphates (Patp and betaATP), and
      calculated concentrations of intracellular ionized magnesium (Mgi) and H(+) ions
      between the groups were detected. Systolic blood pressure correlates positively
      with PCr/Patp (r = 0.43, P < .05), Pi/Patp (r = 0.413, P < .05), and Pi/betaATP
      (r = 0.48, P < .05). Diastolic blood pressure correlates positively only with the
      ratio Pi/betaATP (r = 0.42, P < .05). The sum of immunoreactive insulin values
      correlates with PCr/betaATP (r = 0.53, P < .01) and with Pi/betaATP (r = 0.6, P <
      .01). In conclusion, increase in blood pressure and insulin resistance were
      confirmed in offspring of OH. Insulin sensitivity is related to sMg and the
      elevation of blood pressure is associated with the activation of energy
      metabolism in skeletal muscle. The relationship between muscle energetic
      characteristics and markers of insulin resistance suggests that the alteration of
      energy metabolism may be present in early stages of metabolic syndrome.

PMID- 16979412
TI  - Short- and long-term insulin-like effects of monoamine oxidases and semicarbazide
      sensitive amine oxidase substrates in cultured adipocytes.
AB  - Semicarbazide-sensitive amine oxidase (SSAO) is known to increase during in vitro
      adipogenesis and to be one of the most highly expressed membrane proteins of
      white adipocytes. Although less well documented, mitochondrial monoamine oxidases
      (MAOs) are also present in adipocytes and share with SSAO the capacity to
      generate hydrogen peroxide. This work therefore aimed to compare several biologic
      effects of MAO and SSAO substrates in 3T3-F442A adipocytes. In differentiated
      cells, tyramine oxidation was predominantly MAO dependent, whereas benzylamine
      oxidation was SSAO dependent. Both amines partially mimicked insulin actions,
      including stimulation of Akt phosphorylation and glucose uptake. In addition,
      tyramine and benzylamine impaired tumor necrosis factor alpha-dependent nitric
      oxide formation in a pargyline- and semicarbazide-sensitive manner, respectively.
      Various biogenic amines were tested in competition for tyramine or benzylamine
      oxidation and classified as MAO-preferring (methoxytyramine, tryptamine) or SSAO
      preferring substrates (methylamine, octopamine). Short-term incubation with 1
      mmol/L of all amines except histamine stimulated glucose uptake up to 20% to 50%
      of maximal insulin activation. One-week treatment with either MAO or SSAO
      substrates alone allowed postconfluent cells to differentiate into adipocytes,
      reproducing 60% of insulin-promoted lipid accumulation. All amines also exerted a
      slight improvement in the adipogenic action of insulin. Therefore, like SSAO,
      substrate activation of MAO can interact with adipocyte metabolism by mimicking
      diverse effects of insulin in addition to preventing tumor necrosis factor alpha
      dependent responses.

PMID- 16979413
TI  - Relationship between polymorphisms 804C/A and 252A/G of lymphotoxin-alpha gene
      and -308G/A of tumor necrosis factor alpha gene and diabetic retinopathy in
      Japanese patients with type 2 diabetes mellitus.
AB  - To clarify whether polymorphisms of the lymphotoxin-alpha (LTA) gene and tumor
      necrosis factor alpha (TNF-alpha) gene were related to diabetic retinopathy (DR),
      we performed a case-control study in 251 Japanese patients with type 2 diabetes
      mellitus participating in a multicenter research protocol. Genetic analyses were
      performed by using a fluorescent allele-specific DNA primer assay system.
      Diabetic retinopathy was diagnosed in a masked manner by an independent
      ophthalmologist using fundus photographs and was classified as nondiabetic
      retinopathy (NDR), nonproliferative retinopathy (NPDR), and proliferative
      retinopathy (PDR). The results showed that the genotype frequencies of 804C/A in
      exon 3 and 252A/G in intron 1 of the LTA gene were not significantly different
      among patients with NDR, NPDR, and PDR. A allelic frequency of the TNF-alpha gene
      (-302A/G in promoter) was also identical among NDR, NPDR, and PDR groups.
      Multivariate logistic regression analyses showed that significant associations
      with DR were glycosylated hemoglobin level and diabetes duration, but not
      polymorphisms of the LTA gene or TNF-alpha gene. In conclusion, the present study
      showed no association between polymorphisms 804C/A and 252A/G of the LTA gene and
      -302A/G of the TNF-alpha gene and DR in Japanese type 2 diabetic patients.

PMID- 16979415
TI  - Sequencing analysis of ghrelin gene 5' flanking region: relations between the
      sequence variants, fasting plasma total ghrelin concentrations, and body mass
      index.
AB  - Ghrelin is a 28-amino-acid peptide with several functions linked to energy
      metabolism. Low ghrelin plasma concentrations are associated with obesity,
      hypertension, and type 2 diabetes mellitus, whereas high concentrations reflect
      states of negative energy balance. Several studies addressing the hormonal and
      neural regulation of ghrelin gene expression have been carried out, but the role
      of genetic factors in the regulation of ghrelin plasma levels remains unclear. To
      elucidate the role of genetic factors in the regulation of ghrelin expression, we
      screened 1657 nucleotides of the ghrelin gene 5' flanking region (promoter and
      possible regulatory sites) for new sequential variations from patient samples
      with low (n = 50) and high (n = 50) fasting plasma total ghrelin concentrations
      (low- and high-ghrelin groups). Eleven single nucleotide polymorphisms (SNPs), 3
      of which were rare variants (allelic frequency less than 1%) were found in our
      population. The genotype distribution patterns of the SNPs did not differ between
      the study groups, except for SNP-501A>C (P = .039). In addition, the SNP-01A>C
      was associated with body mass index (BMI) (P = .018). This variant was studied
      further in our large and well-defined Oulu Project Elucidating Risk for
      Atherosclerosis (OPERA) cohort (n = 1045) by the restriction fragment length
      polymorphism (RFLP) technique. No significant association of SNP-501A>C genotypes
      with fasting ghrelin plasma concentrations was found in the whole OPERA
      population. However, the association of this SNP with BMI and with waist
      circumference reached statistical significance in OPERA (P = .047 and .049,
      respectively), remaining of borderline significance for BMI after adjustments (P
      = .055). The results indicate that factors other than the 11 SNPs found in this
      study in the 5' flanking region of ghrelin gene are the main determinants of
      ghrelin plasma levels. However, SNP-501 A>C genotype distribution seems to be
      different in subjects having the highest compared with those with the lowest
      ghrelin levels, and the SNP may be associated with BMI and waist circumference.

PMID- 16979414
TI  - The messenger RNA profiles in liver, hypothalamus, white adipose tissue, and
      skeletal muscle of female Zucker diabetic fatty rats after topiramate treatment.
AB  - Topiramate (TPM) is a novel neurotherapeutic agent approved for the treatment of
      epilepsy and for migraine prophylaxis. It has been observed that in obese
      associated, type 2 diabetic rodent models, TPM treatment reduced the body weight
      gain, improved insulin sensitivity, and enhanced glucose-regulated insulin
      release. A long-term treatment with TPM thus ameliorated obesity and diabetic
      syndromes in female Zucker diabetic fatty rats and db/db mice. The molecular
      mechanisms of TPM antiobesity and antidiabetic effects remain unknown. We have
      applied DNA microarray technology to explore genes that might be involved in the
      mechanisms by which TPM improves insulin sensitivity and blood glucose handling,
      as well as body weight control. In female Zucker diabetic fatty rats, 7-day TPM
      treatment significantly reduced the plasma levels of glucose and triglyceride in
      a dose-dependent manner. The DNA microarray data revealed that TPM treatment
      altered messenger RNA profiles in liver, hypothalamus, white adipose tissue, and
      skeletal muscle. The most marked effect of TPM on gene expression occurred in
      liver with those genes related with metabolic enzymes and signaling regulatory
      proteins involved in energy metabolism. TPM treatment decreased messenger RNA
      amounts for sterol regulatory element binding protein-1c, stearoyl-coenzyme A
      (CoA) desaturase-1, choline kinase, and fatty acid CoA ligase, long chain 4. TPM
      also up-regulated 3 cholesterol synthesis genes. In addition, the short-term
      effect of TPM on gene expression was examined at 16 hours after a single
      administration. TPM markedly reduced hepatic expression of genes related with
      fatty acid synthesis, eg, stearoyl-CoA desaturase and acetyl-CoA carboxylase. TPM
      also changed genes related with fatty acid beta-oxidation, increased 3-2-trans
      enoyl-CoA isomerase and mitochondrial acyl-CoA thioesterase, and decreased fatty
      acid CoA ligase (long chain 2 and long chain 5). These gene expression changes
      were independent of food intake as shown by pair feeding. Our results suggest
      that TPM regulates hepatic expression of genes involved in lipid metabolism,
      which could be part of the mechanisms by which TPM reduces plasma triglyceride
      levels in obese diabetic rodents.

PMID- 16979416
TI  - Oxidizing and reducing responses of granulocytes from type 2 diabetic patients.
AB  - Oxidizing/reducing response by granulocytes and a potential correlation between
      reactive oxygen species generation and triglyceride, total cholesterol, low
      density lipoprotein, high-density lipoprotein, body mass index, fasting plasma
      glucose, glycemic control (hemoglobin A(1c)), or duration of diabetes were
      examined in type 2 diabetic patients and in healthy subjects. An increase in both
      oxidizing and reducing responses was observed in cells from diabetic patients
      relative to normoglycemic individuals. The increase in oxidizing response was
      nearly 2-fold higher, whereas the antioxidant response increased by 50%. Although
      reactive oxygen species generation from healthy subjects was correlated with
      levels of low-density lipoprotein (positive correlation), high-density
      lipoprotein (negative correlation), and body mass index (positive correlation),
      no such associations were observed in diabetic subjects, suggesting either an
      intrinsic perturbation in the oxidant/antioxidant response or possibly due to the
      effect of the various medications being taken by these patients. These issues
      need further study.

PMID- 16979417
TI  - Differences in maternal protein intake in pregnant rats alone alter the
      docosahexaenoic acid concentration in the fetal and adult offspring.

PMID- 16979420
TI  - The pharmacology of wakefulness.
AB  - Being awake, alert, and able to function in our 24-7 world is a challenge in the
      face of the fatigue and sleepiness engendered by long work hours, unusual work
      schedules, sickness, and other factors. Development of effective treatments to
      combat fatigue and sleepiness requires an understanding of the neurobiology of
      wakefulness. In this brief review, we examine the neuroanatomical, neurochemical,
      and molecular basis of the wakeful state to provide a framework for understanding
      current and future pharmacologic approaches to modification of wakefulness. The
      spontaneously awake state can be defined as a natural state of vigilance or
      arousal differing from natural sleep in both behavior and neural activity. These
      differences have long intrigued researchers and largely have been characterized
      in the brain areas and neurochemical systems affecting the sleep and wake states.
      Many of the strategies for promoting the awake condition involve manipulation or
      modulation of specific neurochemical systems with the ultimate goal of enhancing
      wakefulness, diminishing sleepiness, or both. Wakefulness is an important
      cortical function that depends on the coordinated effort of multiple brain areas
      including the thalamus, hypothalamus, and basal forebrain to integrate and relay
      information from the brainstem to the cortex. Norepinephrine and serotonin-long
      considered arousal-enhancing transmitters as well as glutamate, acetylcholine,
      histamine, and the neuromodulators hypocretin-orexins and adenosine, are known to
      affect the signal transduction in these brain areas and initiate, promote, or
      enhance wakefulness. Use of molecular tools to evaluate the awake, asleep, and
      sleep-deprived state has revealed novel insights concerning the gene expression
      events associated with wakefulness. Understanding wakefulness at this level
      undoubtedly will contribute to the development of pharmacologic approaches to
      promote or enhance the wakeful state. We caution, however, that sleep may have a
      necessary, restorative function for the brain; therefore, prolonging wakefulness
      for long periods through artificial means could have unexpected and perhaps
      detrimental consequences on brain health.

PMID- 16979421
TI  - Neurobiology of sleep.
AB  - The central nervous system undergoes several dynamic changes during sleep, which
      are coordinated by the pons, basal forebrain areas, and other subcortical
      structures and are mediated by three major neurotransmitters-norepinephrine,
      serotonin, and acetylcholine. The neuronal populations that produce these
      neuromodulators constitute the central representation of the sympathetic and
      parasympathetic subdivisions of the autonomic nervous system. The locus coeruleus
      (noradrenergic) and the raphe nucleus (serotoninergic) are most active during
      waking and become progressively less active in the transition from non-rapid eye
      movement (non-REM) to rapid eye movement (REM) sleep. On the other hand, the
      cholinergic neurons in the dorsolateral tegmental and pedunculopontine nuclei
      area are active both during waking and REM sleep. Over the past decade, a number
      of studies have provided interesting new evidence supporting the role of sleep in
      sleep-dependent memory processing. These studies have been directed specifically
      towards the role of sleep in memory encoding, memory consolidation, brain
      plasticity and memory reconsolidation, and have confirmed the hypothesis that
      sleep contributes importantly to processes of memory and brain plasticity. It has
      been shown in humans that sleep triggers overnight learning on a motor-sequence
      memory task, while equivalent waking periods produce no such improvement. These
      findings have important implications for acquiring real-life skills and in
      clinical rehabilitation following brain trauma and stroke.

PMID- 16979422
TI  - Sleep deprivation as a neurobiologic and physiologic stressor: Allostasis and
      allostatic load.
AB  - Sleep has important homeostatic functions, and sleep deprivation is a stressor
      that has consequences for the brain, as well as many body systems. Whether sleep
      deprivation is due to anxiety, depression, or a hectic lifestyle, there are
      consequences of chronic sleep deprivation that impair brain functions and
      contribute to allostatic load throughout the body. Allostatic load refers to the
      cumulative wear and tear on body systems caused by too much stress and/or
      inefficient management of the systems that promote adaptation through allostasis.
      Chronic sleep deprivation in young healthy volunteers has been reported to
      increase appetite and energy expenditure, increase levels of proinflammatory
      cytokines, decrease parasympathetic and increase sympathetic tone, increase blood
      pressure, increase evening cortisol levels, as well as elevate insulin and blood
      glucose. Repeated stress in animal models causes brain regions involved in memory
      and emotions, such as hippocampus, amygdala, and prefrontal cortex, to undergo
      structural remodeling with the result that memory is impaired and anxiety and
      aggression are increased. Structural and functional magnetic resonance imaging
      studies in depression and Cushing's disease, as well as anxiety disorders,
      provide evidence that the human brain may be similarly affected. Moreover, brain
      regions such as the hippocampus are sensitive to glucose and insulin, and both
      type 1 and type 2 diabetes mellitus are associated with cognitive impairment and
      (for type 2 diabetes mellitus) increased risk for Alzheimer's disease. Animal
      models of chronic sleep deprivation indicate that memory is impaired along with
      depletion of glycogen stores and increases in oxidative stress and free radical
      production. Taken together, these changes in brain and body are further evidence
      that sleep deprivation is a chronic stressor and that the resulting allostatic
      load can contribute to cognitive problems, which can, in turn, further exacerbate
      pathways that lead to disease.

PMID- 16979424
TI  - Sleep and energy balance: Interactive homeostatic systems.
AB  - For early humans, acquisition of food by hunting and/or gathering was a hunger
      driven process requiring vigilance and (often) strenuous physical effort during
      daylight hours. To sustain such activities, hunter-gatherers also needed periodic
      rest and sleep-pursuits most effectively undertaken at night. In recent years,
      research has given us new insights into the physiologic underpinnings of these
      behaviors. Specifically, evidence has been uncovered indicating that the
      homeostatic regulation of food intake on the one hand and that of sleep on the
      other hand, are intertwined. Thus, carefully performed studies of eating behavior
      in rats indicate that duration of sleep after ingestion of a meal is closely
      correlated to the meal's energy content. In 1999, it was discovered that mice and
      dogs functionally deficient in the appetite-stimulating hormone, hypocretin-1,
      become narcoleptic, suggesting the existence of a "hard-wired" connection between
      regulation of hunger and satiety and regulation of sleep. Administered into the
      nucleus accumbens shell, hypocretin-1 induces feeding and locomotor activity in
      Sprague-Dawley rats. Hypocretin neurons in the hypothalamus are responsive to
      metabolic cues capable of signaling nutritional status. The suprachiasmatic
      nucleus, the body's principal circadian clock, exchanges information with the
      hypocretin system about the light/dark cycle and the body's metabolic condition.
      Circadian Clock mutant mice exhibit an attenuated diurnal feeding rhythm and
      become hyperphagic and obese. Both disruption of the circadian cycle and sleep
      deprivation can affect energy balance and, over time, may bring about substantial
      changes in body composition. Although there is growing evidence that interleukin
      6 and several other proinflammatory cytokines are "sleep factors" that also
      affect energy balance, any possible role they might have in coordinating
      sleep/wakefulness with food-motivated behavior awaits clarification. Yet, the
      evidence is increasingly strong that the neurophysiologic and metabolic
      mechanisms responsible for the control of food-seeking behavior and the control
      of sleep and wakefulness are coordinated so that hunger and vigilance are paired
      during the daylight hours, and satiety and sleep are paired during darkness. The
      hypothalamic neuronal system that links these mechanisms is predominantly, but
      not exclusively, hypocretinergic, and is responsive to the suprachiasmatic
      nucleus circadian pacemaker and to certain metabolic signals of depletion and
      repletion.

PMID- 16979423
TI  - Metabolic mechanism of wakefulness (and hunger) and sleep (and satiety): Role of
      adenosine triphosphate and hypocretin and other peptides.
AB  - The concurrent background level of metabolic activity may control state of
      vigilance, promoting wakefulness (and hunger) when it is low, or sleep (and
      satiety) when it is high. In a series of experiments, we have shown that sleep is
      dependent on feeding, but only because of the metabolic consequences of food
      ingestion. These consequences are sensed by glioneuronal populations (at least in
      the rostromedial hypothalamus), which probably respond to channel-bound adenosine
      triphosphate/diphosphate turnover (ischymetric monitoring) rather than to the
      binding of such downstream molecules as adenosine and cytochrome c oxidase. This
      basic signal is communicated to the vigilance-controlling centers by a cascade of
      peptidic and nonpeptidic messengers-messengers that promote wakefulness and
      hunger, possibly via a hypometabolic action (as in the case of neuropeptide Y or
      hypocretins), or somnolence and satiety, possibly via a hypermetabolic action (as
      in the case of leptin or certain serotonergic agents).

PMID- 16979425
TI  - Narcolepsy and the hypocretins.
AB  - Narcolepsy is a chronic neurologic disease characterized by excessive daytime
      sleepiness and one or more of three additional symptoms (cataplexy, or sudden
      loss of muscle tone; vivid hallucinations; and brief periods of total paralysis)
      related to the occurrence of rapid eye movement (REM) sleep at inappropriate
      times. The daytime sleepiness typically presents as a sudden overwhelming urge to
      sleep, followed by periods of sleep that last for seconds or minutes, or even
      longer. During daytime sleep episodes, patients may exhibit "automatic behavior,"
      performing conventionalized functions (eg, taking notes), but not remembering
      having done so once they are awake. About 10% of narcoleptics are members of
      familial clusters; however, genetic factors alone are apparently insufficient to
      cause the disease, inasmuch as the most common genetic disorder, a mutation in
      chromosome 6 controlling the HLA antigen immune complex, although seen in 90% to
      100% of patients, also occurs in as many as 50% of people without narcolepsy. A
      dog model of narcolepsy exhibits a mutation on chromosome 12 that disrupts the
      processing of the peptide neurotransmitter hypocretin. No such mutation
      characterizes human narcolepsy; however, cerebrospinal fluid (CSF) hypocretin
      levels are profoundly depressed in narcoleptic patients, and a specific reduction
      in hypocretin-containing neurons has been described. One hypothesis concerning
      the pathophysiology of narcolepsy proposes that the HLA subtype resulting from
      the mutation on chromosome 6 increases the susceptibility of hypocretin
      containing brain neurons to immune attack. Because hypocretin may normally
      participate in the maintenance of wakefulness, the loss of neurons that release
      this peptide might allow REM sleep to occur at inappropriate times, ie, while the
      patient is awake, in contrast to its normal cyclic appearance after a period of
      slow-wave sleep. The cataplexy, hallucinations, and/or paralysis associated with
      REM episodes normally are unnoticed-or, at least, not remembered-when the
      transition to REM follows slow wave sleep, as is normally the case; however, they
      are remembered when, in people with narcolepsy, the REM episode starts during a
      period of wakefulness. The association of narcolepsy with a deficiency in a
      specific neurotransmitter, in this case, hypocretin, is reminiscent of the
      associations between Parkinson disease and dopamine, or early Alzheimer disease
      and acetylcholine.

PMID- 16979426
TI  - Sleep disorders in psychiatry.
AB  - Sleep is an active state that is critical for our physical, mental, and emotional
      well-being. Sleep is also important for optimal cognitive functioning, and sleep
      disruption results in functional impairment. Insomnia is the most common sleep
      disorder in psychiatry. At any given time, 50% of adults are affected with 1 or
      more sleep problems such as difficulty in falling or staying asleep, in staying
      awake, or in adhering to a consistent sleep/wake schedule. Narcolepsy affects as
      many individuals as does multiple sclerosis or Parkinson disease. Sleep problems
      are especially prevalent in schizophrenia, depression, and other mental
      illnesses, and every year, sleep disorders, sleep deprivation, and sleepiness add
      billions to the national health care bill in industrialized countries. Although
      psychiatrists often treat patients with insomnia secondary to depression, most
      patients discuss their insomnia with general care physicians, making it important
      to provide this group with clear guidelines for the diagnosis and management of
      insomnia. Once the specific medical, behavioral, or psychiatric causes of the
      sleep problem have been identified, appropriate treatment can be undertaken.
      Chronic insomnia has multiple causes arising from medical disorders, psychiatric
      disorders, primary sleep disorders, circadian rhythm disorders, social or
      therapeutic use of drugs, or maladaptive behaviors. The emerging concepts of
      sleep neurophysiology are consistent with the cholinergic-aminergic imbalance
      hypothesis of mood disorders, which proposes that depression is associated with
      an increased ratio of central cholinergic to aminergic neurotransmission. The
      characteristic sleep abnormalities of depression may reflect a relative
      predominance of cholinergic activity. Antidepressant medications presumably
      reduce rapid eye movement (REM) sleep either by their anticholinergic properties
      or by enhancing aminergic neurotransmission. Intense and prolonged dreams often
      accompany abrupt withdrawal from antidepressant drugs, a reflection of an REM
      rebound after drug-induced REM deprivation. The postulated link between sleep and
      psychiatric disorders has been reinforced by the findings of modern neurobiology.

PMID- 16979427
TI  - Sleep and vascular disorders.
AB  - It is not surprising that cardiovascular diseases such as congestive heart
      failure and coronary insufficiency can give rise to varying degrees of sleep
      impairment; it is less readily appreciated that certain physiologic events
      occurring during sleep-as well as long-term unsatisfactory sleep-may cause or
      increase the risk of cardiovascular conditions such as hypertension,
      atherosclerosis, stroke, and cardiac arrythmias. Heart rate abnormalities during
      sleep in normotensive subjects predict later cardiovascular disease, and their
      early identification alerts the physician to undertake preventive measures.
      Maneuvers, such as induction of hypoxia, can elicit abnormal blood pressure
      responses during sleep, and such responses have been used to identify impending
      cardiovascular problems that could become therapeutic targets. The spontaneously
      hypertensive rat has been used to examine the effect of sympathetic nervous
      system (SNS) activity on the heart under a variety of experimental conditions,
      including quiet and paradoxical sleep. The results have disclosed significant
      differences between the responses of spontaneously hypertensive rats and normal
      rats to SNS stimulation. Exploration of other pathophysiologic pathways affected
      by exposure to light and dark, including those responsive to the cyclic
      production of melatonin, will improve our understanding of the effect of
      disruptions of the circadian cycle on cardiovascular function. There is growing
      evidence that melatonin can influence important processes such as fluid,
      nitrogen, and acid-base balance. Human subjects whose nocturnal arterial blood
      pressure fails to show the "normal" decrement during sleep ("nondippers") are
      also prone to sleep poorly, exhibit increased SNS activity during sleep, and have
      an increased risk of total and cardiovascular disease mortality. Chronic sleep
      deficit is now known to be a risk factor for obesity and may contribute to the
      visceral form of obesity that underlies the metabolic syndrome. The rising
      prevalence of obstructive sleep apnea and central sleep apnea is linked to the
      modern-day epidemic of obesity. Obstructive sleep apnea is associated with an
      enhanced risk of having a new stroke or a transient ischemic attack.

PMID- 16979428
TI  - The interdependence of sleep and health--a commentary.

PMID- 16979429
TI  - Genetics of the sleep-wake cycle and its disorders.
AB  - The sleep-wake cycle is under the control of the circadian clock. Recent advances
      in rhythm biology have identified molecular clocks and their key regulating
      genes. Circadian clock genes (Clock, Per) were first isolated in Drosophila, and
      their homologous counterparts have been found in mammals. Some of the circadian
      master genes have been shown to influence sleeping behavior. For instance, a
      point mutation in a human clock gene (Per2) was shown to produce the rare
      advanced sleep phase syndrome, whereas a functional polymorphism in Per3 is
      associated with the more frequent delayed sleep phase syndrome. Furthermore, a
      study examining the association between Clock gene polymorphisms and insomnia
      revealed a higher recurrence of initial, middle, and terminal insomnia in
      patients homozygous for the Clock genotype. Other genes have been shown to
      contribute to sleep pathologies. A point mutation in the prion protein gene
      appears to be the cause of fatal familial insomnia. A missense mutation has been
      found in the gene encoding the GABA-A beta 3 subunit in a patient with chronic
      insomnia. In both animal models and humans, a deficiency in the hypocretin/orexin
      system was proposed to be responsible for narcolepsy. Selective destruction of
      hypocretin neurons is the most probable culprit in humans. These findings suggest
      that the genetic contribution to sleep disorders and wake determinants is more
      important than originally thought. Beyond sleep, light/dark cycles and sleep
      deprivation appear also to be associated with eating habits, and epidemics of
      obesity have to be evaluated in the context of shortened sleep duration.

PMID- 16979430
TI  - Time to include high-risk early ovarian cancer in randomized phase III trials of
      advanced ovarian cancer.

PMID- 16979432
TI  - Cervical cancer prevention in the era of prophylactic vaccines: a preview for
      gynecologic oncologists.
AB  - OBJECTIVE: The recent approval of a vaccine to prevent HPV infection is an
      important advance in cervical cancer prevention. This article is intended to
      provide gynecologic oncologists with a comprehensive background in modern
      cervical cancer prevention strategies. METHODS: We describe and contrast the
      quadrivalent and bivalent vaccines. More established cervical cancer prevention
      strategies are reviewed, with comments on the impact of HPV vaccination. Clinical
      guidance is provided for use of the approved quadrivalent vaccine. Safety and
      side effects of both vaccines are reviewed and future questions and challenges
      are explored. RESULTS: It is vitally important that both vaccinated and
      unvaccinated women continue to fully engage in cervical cancer prevention,
      including cervical cancer screening, follow-up of abnormal screens, and treatment
      of premalignant lesions. A quadrivalent virus-like particle vaccine has now been
      approved for use in girls and women ages 9 to 26. A bivalent vaccine may be
      available soon. Vaccine efficacy in clinical trials has been outstanding, with
      100% protection against HPV-type-specific cervical intraepithelial neoplasia
      (CIN) II and III. CONCLUSIONS: Comprehensive cervical cancer protection now
      includes prophylactic vaccination for girls and young women in addition to
      screening and treatment of premalignant changes. Gynecologic oncologists will
      continue to play an important role in promoting optimal prevention practices.

PMID- 16979433
TI  - Clinical development of radioimmunotherapy for B-cell non-Hodgkin's lymphoma.
AB  - Over the past several decades, several biomolecules have been investigated for
      their ability to deliver radiation to cancer cells, but antibodies have been the
      carriers of choice in systemic targeted radionuclide therapy (STaRT). Two
      radioimmunotherapy agents that target the CD20 antigen, (131)I-tositumomab and
      (90)Y-ibritumomab tiuxetan, have been approved by the U.S. Food and Drug
      Administration for the treatment of patients with relapsed or refractory B-cell
      non-Hodgkin's lymphoma (NHL), and clinical trials have shown that they are
      effective as monotherapies in the salvage setting, producing response rates that
      are often higher and durations of response that are often longer than those with
      chemotherapy. Escalated doses of these agents can be supported with stem cell
      transplantation and can produce high rates of complete response and greater
      survival in patients with relapsed NHL. The quality and duration of responses are
      greater with radioimmunotherapy when it is used earlier in the course of
      treatment.

PMID- 16979434
TI  - Summary of systemic targeted radionuclide therapy symposium.

PMID- 16979435
TI  - Ongoing investigations and new uses of radioimmunotherapy in the treatment of non
      Hodgkin's lymphoma.
AB  - Studies in radiation oncology are focusing on the optimal use of systemic
      targeted radionuclide therapy (STaRT) in the treatment of patients with cancer.
      The two approved radioimmunotherapy agents, yttrium-90 ibritumomab tiuxetan and
      iodine-131 tositumomab, are being studied in a range of lymphoid malignancies,
      from low-grade to aggressive B-cell non-Hodgkin's lymphomas. Studies of standard-
      and escalated-dose radioimmunotherapy with or without stem cell support are
      reviewed, as are radioimmunotherapy with other therapeutic modalities in these
      settings. The results of these trials have important implications for clinical
      practice, and it is hoped that they will further clarify the optimal timing and
      dosing of these agents.

PMID- 16979436
TI  - Iodine-131 tositumomab (Bexxar) in a radiation oncology environment.
AB  - Iodine-131 (I-131) tositumomab (Bexxar; GlaxoSmithKline, Research Triangle Park,
      NC) is one of two recently approved radiolabeled antibodies directed against the
      CD20 surface antigen found on normal B cells and in more than 95% of B cell non
      Hodgkin's lymphoma. The compound itself is formulated as an IgG2a immunoglobulin
      radiolabeled with the mixed beta/gamma emitter I-131. Multicenter clinical trials
      have repeatedly shown impressive clinical responses (20-40% complete response
      rates and 60-80% overall response rates) in the patient groups for whom this
      treatment is indicated. Treatment-related toxicity is generally extremely mild
      and typically involves only reversible hematopoietic suppression and (in some
      cases) a risk of treatment-induced hypothyroidism. Owing to the radiation safety
      concerns necessitated by the clinical use of this targeted radiopharmaceutical,
      it is important for radiation oncology departments wishing to participate in the
      care of these patients to establish methodologies and standard operating
      procedures for safe and efficient departmental use. This summary reviews the
      pertinent background information related to the current clinical experience with
      I-131 tositumomab and highlights some of the major opportunities for the
      participation of radiation oncology in the patient evaluation and treatment
      process. I-131 tositumomab provides an excellent example of the way in which the
      increasingly important new field of "targeted therapy" intersects with the
      practice of clinical radiotherapy. The author contends that it will be worth the
      time and effort involved in establishing a firm basis for the development of a
      comprehensive program for systemic targeted radiopharmaceutical therapies (STaRT)
      within the radiation medicine domain.

PMID- 16979438
TI  - Overview of dosimetry for Systemic Targeted Radionuclide Therapy (STaRT).
AB  - The purposes of systemic targeted radionuclide therapy dosimetry include
      compiling a database of normal organ radiation-absorbed doses that are carrier-
      and radionuclide-specific, and assuring that the normal organ radiation doses are
      within a safe range before therapy. Also of importance is quantitation of
      radiation delivery to tumors vs. normal tissues to correlate absorbed dose with
      tumor control. For agents with significant and variable excretion, estimates of
      individual patient distribution/clearance may be needed to optimize the dose
      response relationship.

PMID- 16979437
TI  - Logistics of therapy with the ibritumomab tiuxetan regimen.
AB  - Radioimmunotherapy is an important new modality for treating patients with B-cell
      non-Hodgkin's lymphoma (NHL). Clinical trials have shown the safety and efficacy
      of agents that deliver radiation directly to malignant cells by attaching the
      (131)I or (90)Y radionuclide to monoclonal antibodies against CD20. In clinical
      trials, (90)Y ibritumomab tiuxetan has produced rates of response as high as 83%
      in patients with relapsed or refractory CD20+ NHL. The ibritumomab tiuxetan
      regimen is conveniently given in an outpatient setting over the course of 7-9
      days. This article describes the logistics for initiating treatment, coordinating
      a multidisciplinary team, identifying eligible patients, and delivering the
      imaging and therapeutic doses of ibritumomab tiuxetan. The standard radiation
      safety procedures to protect family members and healthcare professionals involved
      in the care of patients treated with (90)Y ibritumomab tiuxetan are also
      reviewed. Treatment with the ibritumomab tiuxetan regimen involves only standard
      precautions needed to minimize radiation exposure to other persons.

PMID- 16979439
TI  - Radioimmunotherapy in a radiation oncology environment: building a multi
      specialty team.
AB  - Radioimmunotherapy (RIT) is a new branch of radiation medicine in which
      antibodies specific for tumor-associated antigens are linked to radioactive atoms
      to provide biologically targeted short-range molecular radiotherapy. Two such
      biologically targeted radiopharmaceuticals have been approved for commercial use
      in the last few years. Y-90 ibritumomab tiuxetan (Zevalin) and I-131 tositumomab
      (Bexxar) both recognize the CD-20 surface antigen found on normal and malignant B
      cells. Both of these compounds produce impressive clinical results when used in
      the management of indolent, refractory, and transformed CD-20+ B-cell non
      Hodgkin's lymphoma, but the unsealed sources involved in this class of compounds
      also require new types of patient care coordination and patient/environmental
      safety procedures. Because these multifunctional compounds are ideally
      administered through a multi-departmental team approach, the planning process to
      initiate and direct such a team is quite important. This article reviews some of
      the key processes that may be necessary to establish a successful clinical RIT
      team. The manuscript highlights the important roles that the radiation oncology
      team members may play in this multi-department enterprise.

PMID- 16979440
TI  - Cure of incurable lymphoma.
AB  - The most potent method for augmenting the cytocidal power of monoclonal antibody
      (MAb) treatment is to conjugate radionuclides to the MAb to deliver systemic
      radiotherapy (radioimmunotherapy; RIT). The antigen, MAb, and its epitope can
      make a difference in the performance of the drug. Additionally, the radionuclide,
      radiochemistry, chelator for radiometals and the linker between the MAb and
      chelator can have a major influence on the performance of drugs
      (radiopharmaceuticals) for RIT. Smaller radionuclide carriers, such as antibody
      fragments and mimics, and those used for pretargeting strategies, have been
      described and evaluated. All of these changes in the drugs and strategies for RIT
      have documented potential for improved performance and patient outcomes. RIT is a
      promising new therapy that should be incorporated into the management of patients
      with B-cell non-Hodgkin's lymphoma (NHL) soon after these patients have proven
      incurable. Predictable improvements using better drugs, strategies, and
      combinations with other drugs seem certain to make RIT integral to the management
      of patients with NHL, and likely lead to cure of currently incurable NHL.

PMID- 16979441
TI  - Pretargeted radioimmunotherapy.
AB  - This brief review covers the concept of pretargeted radioimmunotherapy and
      summarize the results obtained in preclinical animal models and initial phase I
      clinical trials. Reagents studied have been a bifunctional antibody prepared by
      crosslinking Fab' fragments from two antibodies with different specificity, one
      binding the target antigen expressed on tumors and the other binding a
      radiolabeled peptide. The alternative system is a conjugate of streptavidin
      linked to the pretargeting agent and radiolabeled biotin. After reaching optimal
      tumor targeting of the pretargeting agent, a synthetic mono-biotin poly N-acetyl
      galactosamine compound was used to clear unbound targeting agent from the
      circulation before the injection of radiolabeled biotin. Promising therapeutic
      responses were obtained in various tumor xenograft models in athymic nude mice. A
      phase I study of an anti-CD20/streptavidin pretargeting agent and 15
      mCi/m(2)(90)Y-biotin produced objective responses with minimal toxicity among
      lymphoma patients, with an average tumor-to-whole-body radiation dose ratio of
      49. Pretargeting radioimmunotherapy approaches have shown higher tumor-to-whole
      body ratios than that usually obtained with one-step radioimmunotherapy.

PMID- 16979442
TI  - "Naked" radiopharmaceuticals.
AB  - The term "naked" radiopharmaceuticals, more appropriately, "unbound"
      radiopharmaceuticals, refers to any radioisotope used for clinical research or
      clinical purposes that is not attached to a chemical or biological carrier, and
      that localizes in various tissues because of a physiologic or chemical
      propensity/affinity, or secondary to focal anatomic placement. Although they
      remain useful in selected clinical circumstances, the available agents (except
      for Iodine-131) have been relegated to an unfortunate and somewhat secondary
      role. The agents remain useful and worthy of consideration for new clinical
      investigation and clinical use.

PMID- 16979443
TI  - Selective Internal Radiation Therapy (SIRT) for liver metastases secondary to
      colorectal adenocarcinoma.
AB  - INTRODUCTION: Selective internal radiation therapy (SIRT) is a relatively new
      commercially available microbrachytherapy technique for treatment of malignant
      hepatic lesions using (90)Y embedded in resin microspheres, which are infused
      directly into the hepatic arterial circulation. It is FDA approved for liver
      metastases secondary to colorectal carcinoma and is under investigation for
      treatment of other liver malignancies, such as hepatocellular carcinoma and
      neuroendocrine malignancies. MATERIALS/METHODS: A modest number of clinical
      trials, preclinical animal studies, and dosimetric studies have been reported.
      Here we review several of the more important results. RESULTS: High doses of beta
      radiation can be selectively delivered to tumors, resulting in impressive local
      control and survival rates. Ex vivo analyses have shown that microspheres
      preferentially cluster around the periphery of tumor nodules with a high
      tumor:normal tissue ratio of up to 200:1. Toxicity is usually mild, featuring
      fatigue, anorexia, nausea, abdominal discomfort, and slight elevations of liver
      function tests. CONCLUSIONS: Selective internal radiation therapy represents an
      effective means of controlling liver metastases from colorectal adenocarcinoma.
      Clinical trials have demonstrated improved local control of disease and survival
      with relatively low toxicity. Investigations of SIRT for other hepatic
      malignancies and in combination with newer chemotherapy agents and targeted
      biologic therapies are under way or in planning. A well-integrated team involving
      interventional radiology, nuclear medicine, medical oncology, surgical oncology,
      medical physics, and radiation oncology is essential for a successful program.
      Careful selection of patients through the combined expertise of the team can
      maximize therapeutic efficacy and reduce the potential for adverse effects.

PMID- 16979444
TI  - Systemic Targeted Radionuclide Therapy symposium introduction.

PMID- 16979445
TI  - Systemic targeted radionuclide therapy: potential new areas.
AB  - Radiation oncology is entering an exciting new era with therapies being delivered
      in a targeted fashion through an increasing number of novel approaches. External
      beam radiotherapy now integrates functional and anatomic tumor imaging to guide
      delivery of conformal radiation to the tumor target. Systemic targeted
      radionuclide therapy (STaRT) adds an important new dimension by making available
      to the radiation oncologist biologically targeted radiation therapy. Impressive
      clinical results with antibody-targeted radiotherapy, leading to the Food and
      Drug Administration's approval of two anti-CD20 radiolabeled antibodies,
      highlight the potential of STaRT. Optimization strategies will further improve
      the efficacy of STaRT by improving delivery systems, modifying the tumor
      microenvironment to increase targeted dose, and maximizing dose effect.
      Ultimately, the greatest potential for STaRT will not be as monotherapy, but as
      therapy integrated into established multimodality regimens and used as adjuvant
      or consolidative therapy in patients with minimal or micrometastatic disease.

PMID- 16979446
TI  - Basic immunology of antibody targeted radiotherapy.
AB  - Antibody targeted radiotherapy brings an important new treatment modality to the
      radiation oncology clinic. Radiation dose to tumor and normal tissues are
      determined by a complex interplay of antibody, antigen, tumor, radionuclide, and
      host-related factors. A basic understanding of these immunologic and physiologic
      factors is important to optimally utilize this therapy in the clinic. Preclinical
      and clinical studies need to be continued to broaden our understanding and to
      develop new strategies to further improve the efficacy of this promising form of
      targeted therapy.

PMID- 16979447
TI  - Yttrium-90 microspheres for the treatment of hepatocellular carcinoma: a review.
AB  - To present a critical review of yttrium-90 (TheraSphere) for the treatment of
      hepatocellular carcinoma (HCC). Medical literature databases (Medline, Cochrane
      Library, and CANCERLIT) were searched for available literature concerning the
      treatment of HCC with TheraSphere. These publications were reviewed for
      scientific and clinical validity. Studies pertaining to the use of yttrium-90 for
      HCC date back to the 1960s. The results from the early animal safety studies
      established a radiation exposure range of 50-100 Gy to be used in human studies.
      Phase I dose escalation studies followed, which were instrumental in delineating
      radiation dosimetry and safety parameters in humans. These early studies
      emphasized the importance of differential arteriolar density between
      hypervascular HCC and surrounding liver parenchyma. Current trends in research
      have focused on advancing techniques to safely implement this technology as an
      alternative to traditional methods of treating unresectable HCC, such as external
      beam radiotherapy, conformal beam radiotherapy, ethanol ablation, trans-arterial
      chemoembolization, and radiofrequency ablation. Yttrium-90 (TheraSphere) is an
      outpatient treatment option for HCC. Current and future research should focus on
      implementing multicenter phase II and III trials comparing TheraSphere with other
      therapies for HCC.

PMID- 16979448
TI  - Targeted radionuclide therapy for solid tumors: an overview.
AB  - Although radioimmunotherapy (RIT) has been effective in non-Hodgkin's lymphoma
      (NHL) as a single agent, solid tumors have shown less clinically significant
      therapeutic response to RIT alone. The clinical impact of RIT or other forms of
      targeted radionuclide therapy for solid tumors depends on the development of a
      high therapeutic index (TI) for the tumor vs. normal tissue effect, and the
      implementation of RIT as part of synergistic combined modality therapy (CMRIT).
      Preclinical and clinical studies have provided a wealth of information, and new
      prototypes or paradigms have shed light on future possibilities in many
      instances. Evidence suggests that combination and sequencing of RIT in CMRIT
      appropriately can provide effective treatment for many solid tumors. Vascular
      targets provide RIT enhancement opportunities and nanoparticles may prove to be
      effective carriers for RIT combined with intracellular drug delivery or
      alternating magnetic frequency (AMF) induced thermal tumor necrosis. The sequence
      and timing of combined modality treatments will be of critical importance to
      achieve synergy for therapy while minimizing toxicity. Fortunately, the
      radionuclide used for RIT also provides a signal useful for nondestructive
      quantitation of the influence of sequence and timing of CMRIT on events in
      animals and patients. This can be readily accomplished clinically using
      quantitative high-resolution imaging (e.g., positron emission tomography [PET]).

PMID- 16979449
TI  - National cancer institute perspectives.
AB  - The National Cancer Institute (NCI) Perspectives this year presented information
      on the systemic targeted radionuclide therapy (STaRT) research projects: (1)
      being investigated at the NCI's Intramural Center for Cancer Research; (2) funded
      by NCI's Radiation Research Program and other extramural programs; and (3) the
      appropriate National Institutes of Health/NCI funding mechanisms applicable to
      researchers for obtaining funds for STaRT projects.

PMID- 16979450
TI  - Monitoring county-level vaccination coverage during the 2004-2005 influenza
      season.
AB  - BACKGROUND: During the 2004-2005 influenza season, the United States faced a
      sudden shortage of influenza vaccine. In response, the Centers for Disease
      Control and Prevention (CDC) and the Advisory Committee on Immunization Practices
      (ACIP) recommended prioritizing vaccination for persons aged 65 and older and
      others at high risk. To monitor subsequent vaccination coverage, several
      questions about influenza vaccination were added to the ongoing Behavioral Risk
      Factor Surveillance System (BRFSS). This study provided real-time county-level
      estimates of influenza vaccination coverage from the BRFSS each month from
      October 2004 through January 2005. METHOD: The methods used a variation of small
      area estimation procedures suitable for situations in which most small areas have
      few or no survey respondents, and rapid assessment is essential. Both model-based
      methods and nonparametric spatial-smoothing methods were used in a three-step
      procedure. RESULTS: The highest vaccination rates during the 2004-2005 influenza
      season were seen in the upper Midwest and the Southeast. Areas with the lowest
      vaccination rates were the intermountain West, southern California, portions of
      Washington and Oregon, and various areas across the Eastern United States, often
      coinciding with urban areas. Intrastate variations were especially pronounced in
      the Eastern United States, particularly in Georgia, Florida, Tennessee, Kentucky,
      North Carolina, Virginia, and New York. These states all had areas with low
      immunization rates as well as areas with high rates. CONCLUSIONS: The results
      showed that vaccination coverage varied significantly across states and substate
      regions. Our findings show that this methodology can provide estimates with
      reasonable reliability for planning during public health emergencies.

PMID- 16979451
TI  - The role of attitudes in understanding disparities in adult influenza
      vaccination.
AB  - BACKGROUND: Racial/ethnic disparities in influenza vaccine coverage of adults
      aged 65 years and older persist even after controlling for access, healthcare
      utilization, and socioeconomic status. Differences in attitudes toward
      vaccination may help explain these disparities. The purpose of this study was to
      describe patient characteristics and attitudes toward influenza vaccination among
      whites and African Americans aged 65 years and older, and to examine their effect
      on racial disparities in vaccination coverage. METHODS: A cross-sectional
      telephone survey of Medicare beneficiaries in five U.S. sites, sampled on
      race/ethnicity and ZIP code. Multivariate analysis controlling for demographics,
      healthcare utilization, and attitudes toward influenza vaccination was conducted
      in 2005 to assess racial disparities in vaccine coverage during the 2003-2004
      season. RESULTS: The analysis included 1859 white and 1685 African-American
      respondents; 79% of whites versus 50% of African Americans reported influenza
      vaccination in the past year (p < 0.00001). Both vaccinated and unvaccinated
      African Americans were significantly less likely than whites to report positive
      attitudes toward influenza vaccination. Even among respondents with provider
      recommendations, respondents with positive attitudes were more likely to be
      vaccinated than those with negative attitudes. After multivariate adjustment,
      African Americans had significantly lower odds of influenza vaccination than
      whites (odds ratio = 0.55, 95% confidence interval = 0.42-0.72). CONCLUSIONS: A
      significant gap in vaccination coverage between African Americans and whites
      persisted even after controlling for specific respondent attitudes. Future
      research should focus on other factors such as vaccine-seeking behavior.

PMID- 16979452
TI  - Adults with invasive pneumococcal disease: missed opportunities for vaccination.
AB  - BACKGROUND: The pneumococcal polysaccharide vaccine (PPV) can prevent invasive
      pneumococcal disease (IPD) in the elderly and those with certain underlying
      illnesses. However, vaccine uptake remains suboptimal. Identification of missed
      opportunities for vaccination could guide new strategies for improving uptake.
      Missed opportunities for vaccination were defined as one or more visits to a
      hospital, emergency room (ER), or main provider in the 2 years before infection
      among unvaccinated, adult IPD case-patients with a vaccine indication. METHODS:
      Adults aged 18 years or older with IPD were identified in six Active Bacterial
      Core surveillance/Emerging Infections Program Network sites during a 1-year
      period in 2001 to 2003. Using chart review, patient/proxy interview, a main
      provider questionnaire, and vaccine questionnaires from additional providers,
      data were collected on demographics, vaccine indications, vaccine status, and
      recent healthcare encounters. RESULTS: A total of 1878 cases were enrolled, and
      83% had a vaccine indication. Of the 1177 cases with a vaccine indication and
      sufficient information on recent healthcare encounters, 617 (52%) were
      unvaccinated. Of these, 566 (92%) had one or more opportunities for vaccination,
      54% were hospitalized, 58% had ER visits, and 76% visited their main provider in
      the 2 years before illness. The number of visits to main providers (median = 6)
      was higher than hospitalizations (median = 1), and ER visits (median = 1).
      CONCLUSIONS: One or more missed opportunities for vaccination were documented in
      nearly all unvaccinated IPD case-patients with a vaccine indication. Most visited
      their main provider multiple times. Implementation of systematic PPV programs in
      outpatient settings will likely increase pneumococcal vaccine uptake among high
      risk adults.

PMID- 16979453
TI  - Randomized trial of an intervention to facilitate recycling for relapsed smokers.
AB  - BACKGROUND: Tobacco dependence is a chronic condition requiring repeat treatment
      and long-term follow-up. However, current evidence regarding best approaches to
      providing these services is fairly limited. This study assessed the effectiveness
      of an intervention for increasing repeat tobacco-dependence treatment in a
      population of relapsed smokers. DESIGN: The study was a multicenter randomized
      controlled trial. SETTING/PARTICIPANTS: Patients aged 19 and older receiving a
      prescription for nicotine replacement therapy or bupropion for smoking cessation
      in 2002 at one of five participating Veterans Affairs (VA) facilities were
      eligible. INTERVENTION: A total of 1900 eligible veterans were randomized to (1)
      patient phone call to assess smoking status, quit challenges, and treatment
      preferences, and computerized progress note to providers communicating this
      information (intervention); or (2) usual care (control). MAIN OUTCOME MEASURES:
      Outcomes, assessed in 2003, included the proportion of patients receiving repeat
      pharmacologic or behavioral smoking-cessation treatment in the 6-month follow-up
      period (assessed from VA pharmacy and outpatient data), 7-day point prevalence
      abstinence, and satisfaction (assessed by patient survey). RESULTS: Thirty-four
      percent of intervention participants versus 22% of controls received treatment
      for tobacco dependence in the follow-up period (p = 0.0001). Thirty-two percent
      of intervention participants versus 21% of controls received pharmacologic
      treatment (p = 0.0001), and 12% of intervention subjects versus 8% of controls
      received behavioral treatment (p = 0.005). Abstinence rates at follow-up were 25%
      for intervention subjects and 22% for controls (p = 0.15). Intervention subjects
      were more likely than controls to report being satisfied with the general smoking
      cessation help (87% vs 82%, p = 0.01), as well as the pharmacologic help that
      they received from the VA (89 vs 84%, p = 0.01). CONCLUSIONS: The intervention
      significantly increased repeat treatment rates and satisfaction with services but
      did not have a significant effect on abstinence rates.

PMID- 16979454
TI  - The best practices: use of the guidelines by ten state tobacco control programs.
AB  - BACKGROUND: The Best Practices for Comprehensive Tobacco Control Programs by the
      Centers of Disease Control and Prevention was the first national resource to
      define the nine required components of a comprehensive state tobacco control
      program. This evaluation examined how states used the guidelines in their program
      planning, and identifies strengths and weaknesses of the guidelines. METHODS:
      During 2002-2003, data were collected and analyzed from ten state tobacco control
      programs on familiarity, funding, and use of the guidelines. Data were collected
      via written surveys and qualitative interviews with key tobacco control partners
      in the states. The typical number of participants interviewed was 17,
      representing an average of 15 agencies per state. RESULTS: Lead agencies and
      advisory agencies were the most familiar with the guidelines, while other state
      agencies were less aware of the guidelines. Participants' prioritization of the
      nine components was closely related to the lead agencies' estimated category
      expenditures. Three states modified the guidelines to develop more-tailored
      frameworks. Major strengths of the guidelines included providing a basic program
      framework and state-specific funding recommendations. The guidelines did not
      address implementation strategies or tobacco-related disparities, and had not
      been updated with current evidence-based research. CONCLUSIONS: The guidelines
      are important recommendations for state tobacco control programs. To continue to
      be useful to states, the guidelines need to be updated to address implementation
      and tobacco disparities, and include additional evidence-based examples. Active
      dissemination of updated guidelines needs to be increased beyond typical
      consumers to other tobacco control partners such as coalitions and other state
      agencies.

PMID- 16979455
TI  - Effects of state coalitions to reduce underage drinking: a national evaluation.
AB  - INTRODUCTION: Drinking by youth remains prevalent. The Reducing Underage Drinking
      through coalitions (RUD) project funded ten states for 8 years to form coalitions
      designed to change the policy and normative environment regarding youth access to
      alcohol. An independent national outcome evaluation of this $21-million effort
      was conducted. METHODS: Using a longitudinal quasi-experimental design, the ten
      intervention states were compared with the other 40 states, with repeated annual
      measures of outcomes from 1995 to 2004. Measures included print news media
      coverage, legislative bills enacted, youth drinking behavior, and youth alcohol
      related driving behaviors and traffic crash mortality. Analyses using latent
      growth curve modeling methods were conducted in 2005. RESULTS: Significant
      differences in slopes between treatment and comparison states were found for
      several outcome measures, particularly in the more-proximal outcome domains.
      Across all outcome domains, the pattern of effects was in the direction of
      positive effects of the RUD coalitions, although for most individual measures the
      differences were not statistically significant. The magnitude of observed
      differences associated with the RUD coalitions were sizable, with an estimated
      effect size of 1.10 on media coverage, 0.46 on state policies enacted, -0.44 on
      youth drinking behaviors, and -0.16 on alcohol-related driving and fatal car
      crash mortality. CONCLUSIONS: The pattern of results and the magnitude of
      estimated effects provides evidence of effect of the RUD coalitions. The lack of
      statistically significant differences for most individual outcome measures
      indicates the difficulty of unambiguously demonstrating the full effects of an
      effort designed to change behaviors and health outcomes of the entire youth
      population of multiple states.

PMID- 16979456
TI  - Preventing sudden death with n-3 (omega-3) fatty acids and defibrillators.
AB  - BACKGROUND: Because interventions that prevent and treat events due to
      cardiovascular disease are applied to different, but overlapping, segments of the
      population, it can be difficult to estimate their effectiveness if formal
      calculations are not available. METHODS: Markov chain analysis, including
      sensitivity analysis, was used with a hypothetical population resembling that of
      Olmsted County, MN, aged 30 to 84 in the year 2000 to compare the estimated
      impact of three interventions to prevent sudden death: (1) raising blood levels
      of n-3 (omega-3) fatty acids, (2) distributing automated external defibrillators
      (AEDs), and (3) implanting cardioverter defibrillators (ICDs) in appropriate
      candidates. The analysis was performed in 2004, 2005, and 2006. RESULTS: Raising
      median n-3 fatty acid levels would be expected to lower total mortality by 6.4%
      (range from sensitivity analysis = 1.6% to 10.3%). Distributing AEDs would be
      expected to lower total mortality by 0.8% (0.2% to 1.3%), and implanting ICDs
      would be expected to lower total mortality by 3.3% (0.6% to 8.7%). Three fourths
      of the reduction in total mortality due to n-3 fatty acid augmentation would
      accrue from raising n-3 fatty acid levels in the healthy population. CONCLUSIONS:
      Based on central values of candidacy and efficacy, raising n-3 fatty acid levels
      would have about eight times the impact of distributing AEDs and two times the
      impact of implanting ICDs. Raising n-3 fatty acid levels would also reduce rates
      of sudden death among the subpopulation that does not qualify for ICDs.

PMID- 16979457
TI  - Psychological responses to the sniper attacks: Washington DC area, October 2002.
AB  - BACKGROUND: This study assessed the psychological and behavioral responses of
      residents of the Washington DC metropolitan area to the October 2002 sniper
      shootings, as well as the association between measures of exposure to the
      shootings and elevated traumatic stress symptoms. METHODS: Random-digit-dial
      telephone survey of 1205 adults living in Washington DC and two surrounding
      counties during the shootings, conducted May 2003. Main outcome measures included
      self-reports regarding traumatic stress symptoms, perceptions of safety,
      behavioral responses, and exposures to incidents. RESULTS: Forty-five percent of
      residents reported going to public spaces such as parks and shopping centers less
      than usual, and 5.5% reported missing at least 1 day of work because of the
      sniper attacks. Women who reported living within 5 miles of any shooting incident
      were significantly more likely to report elevated traumatic stress symptoms
      consistent with a probable diagnosis of post-traumatic stress disorder-than women
      who reported living farther from incidents (odds ratio = 4.2, 95% confidence
      interval = 1.9-9.3). Among men, there was no significant association between
      reported residential proximity and elevated traumatic stress symptoms.
      CONCLUSIONS: These results suggest the substantial behavioral and psychological
      impact that traumatic events such as these sniper shootings can have on
      communities. They support the importance of clinicians and community leaders
      addressing psychological functioning in the setting of such events that threaten
      a population. The results further suggest that women who report residing closest
      to such incidents are at greatest risk for experiencing elevated symptoms of
      traumatic stress, and perhaps warrant special attention.

PMID- 16979458
TI  - Physical activities in adolescent girls: variability in energy expenditure.
AB  - BACKGROUND: Understanding interindividual variability of energy expended in
      common activities is important for determining precise estimates of energy
      expenditure in surveillance studies and clinical trials. The purpose of this
      study was to describe the variability in energy expenditure for selected physical
      activities among adolescent girls. METHODS: Seventy-four adolescent girls (aged
      13 to 14 years) participated in this cross-sectional investigation. Data were
      collected in 2001 and analyzed in 2004. Energy expenditure was measured by
      indirect calorimetry for ten activities and during a submaximal cycle ergometer
      test, which was used to estimate cardiorespiratory fitness. Variability in energy
      expended for the various activities was expressed by standard deviation,
      coefficient of variation, and range for three different energy expenditure
      variables: relative VO2 (milliliters per kilogram per minute), absolute VO2
      (liters per minute(-1)), and calculated metabolic rate (kilojoules per minute).
      RESULTS: Depending on the expression of energy expenditure, coefficients of
      variation ranged from a low of 13.2% for climbing stairs to a high of 38.4% for
      playing a computer game. Some lower-intensity activities were associated with
      greater variability in energy expenditure. Bicycling showed consistently higher
      coefficients of variation across expressions of energy expenditure (29.1%, 37.7%,
      and 33.5% for relative VO2, absolute VO2, and calculated metabolic rate,
      respectively). CONCLUSIONS: Energy expenditure for common activities is highly
      variable in adolescent girls. The coefficient of variation was higher in some
      activities of lower intensity, regardless of energy expenditure expression. This
      variance may influence the evaluation of physical activity interventions,
      particularly with regard to issues such as a prescribed dose of activity and the
      statistical power to detect change.

PMID- 16979459
TI  - The rising prevalence of severe poverty in America: a growing threat to public
      health.
AB  - BACKGROUND: The U.S. poverty rate has increased since 2000, but the depth of
      poverty experienced by Americans has been inadequately studied. Of particular
      concern is whether severe poverty is increasing, a trend that would carry
      important public health implications. METHODS: Income-to-poverty (I/P) ratios and
      income deficits/surpluses were examined for the 1990-2004 period. The severely
      poor, moderately poor, and near-poor were classified as those with I/P ratios of
      less than 0.5, 0.5 to 1.0, or 1.0 to 2.0, respectively. Income deficits/surpluses
      were classified relative to the poverty threshold as Tier I (deficit Dollars 8000
      or more), Tier II (deficit or surplus less than Dollars 8000), or Tier III
      (surplus more than Dollars 8000). Odds ratios for severe poverty and Tier I were
      also calculated. RESULTS: Severe poverty increased between 2000 and 2004-those
      with I/P ratios of less than 0.5 grew by 20%, and Tier I grew by 45% to 55%-while
      the prevalence of higher levels of income diminished. The population in severe
      poverty was over-represented by children (odds ratio [OR] = 1.69, confidence
      interval [CI] = 1.63-1.75), African Americans (OR = 2.84, CI = 2.74-2.95), and
      Hispanics (OR = 1.64, CI = 1.58-1.71). CONCLUSIONS: From 2000 to 2004, the
      prevalence of severe poverty increased sharply while the proportion of Americans
      in higher income tiers diminished. These trends have broad societal implications.
      Likely health consequences include a higher prevalence of chronic illnesses, more
      frequent and severe disease complications, and increased demands and costs for
      healthcare services. Adverse effects on children warrant special concern. The
      growth in the number of Americans living in poverty calls for the re-examination
      of policies enacted in recent years to foster economic progress.

PMID- 16979461
TI  - Where best to take a booster break?

PMID- 16979460
TI  - Caring for the underserved: blending service learning and a web-based curriculum.
AB  - BACKGROUND: Recognition of health disparities among underserved individuals,
      whose demographic, geographic, or economic characteristics impede access to
      health-related services, has led to calls for the development of medical school
      curricula that address care for the underserved, but reports of the development
      and evaluation of such curricula are limited. METHODS: Two formats of a
      curriculum addressing care for the underserved were developed and implemented
      during the 6-week pediatric clerkship for third-year medical students during the
      2003-2004 academic year. One format was faculty-led; the other was web-based.
      Skills for providing care to underserved families were taught through didactic,
      experiential, and service-learning curriculum components. Novel core curriculum
      elements included a screening tool for recognizing underserved patients and an
      independent clinical project through which students linked underserved families
      with community health resources. Analyses from 2004-2005 compared pre- and post
      curriculum knowledge and attitudes of web-based students (n = 29) to those
      receiving either the faculty-led (n = 36) or the established "readings-only"
      curriculum (n = 35). Qualitative data from service learning projects were
      analyzed to assess clinical skills. RESULTS: Compared to students in the
      established curriculum, both web-based and faculty-led students demonstrated
      improved knowledge (p < 0.001) and attitudes (p < 0.05) about caring for the
      underserved. Both web-based and faculty-led students were successful in
      recognizing and addressing underserved health issues in the clinical setting.
      CONCLUSIONS: Faculty-led and web-based curricula can equally improve student
      knowledge, attitudes, and skills about caring for the underserved.

PMID- 16979463
TI  - Diffusion and dissemination of physical activity recommendations and programs to
      world populations.

PMID- 16979464
TI  - Need, demand, and external validity in dissemination of physical activity
      programs.

PMID- 16979465
TI  - Physical activity optimizing practice through research.

PMID- 16979466
TI  - A convergent diffusion and social marketing approach for disseminating proven
      approaches to physical activity promotion.
AB  - Approaches from diffusion of innovations and social marketing are used here to
      propose efficient means to promote and enhance the dissemination of evidence
      based physical activity programs. While both approaches have traditionally been
      conceptualized as top-down, center-to-periphery, centralized efforts at social
      change, their operational methods have usually differed. The operational methods
      of diffusion theory have a strong relational emphasis, while the operational
      methods of social marketing have a strong transactional emphasis. Here, we argue
      for a convergence of diffusion of innovation and social marketing principles to
      stimulate the efficient dissemination of proven-effective programs. In general
      terms, we are encouraging a focus on societal sectors as a logical and efficient
      means for enhancing the impact of dissemination efforts. This requires an
      understanding of complex organizations and the functional roles played by
      different individuals in such organizations. In specific terms, ten principles
      are provided for working effectively within societal sectors and enhancing user
      involvement in the processes of adoption and implementation.

PMID- 16979467
TI  - Methodologic challenges in disseminating evidence-based interventions to promote
      physical activity.
AB  - During the past decade, numerous intervention studies have been published on the
      effectiveness of programs to promote active living; however, few studies have
      addressed the dissemination of effective physical activity interventions. Both
      community settings and healthcare settings are important locations for
      dissemination of evidence-based programs and policies. A major gap in the
      existing literature involves the appropriate methodologic approaches for
      planning, evaluating, and reporting on dissemination efforts for effective and
      promising interventions in these locations. To address this gap, two hypothetical
      dissemination studies are presented: a quasi-experimental study of local health
      agencies (Scenario 1) and a group-randomized trial of clinical practices
      (Scenario 2). These studies help to elucidate the barriers and opportunities for
      implementing evidence-based physical activity interventions across different
      settings. Based on the scenarios, the existing literature, and the authors'
      experience, dissemination challenges that researchers and practitioners may
      experience (i.e., issues of design, measures of outcomes and external validity,
      the balance between fidelity and adaptation to local settings, and the review and
      funding of dissemination science) are discussed. Researchers, practitioners, and
      policymakers are invited to address the issues outlined in this article in order
      to bridge the gap between the generation of new knowledge on efficacious physical
      activity interventions and widespread application of these approaches in
      community and clinical settings.

PMID- 16979468
TI  - Evidence-based approaches to dissemination and diffusion of physical activity
      interventions.
AB  - With the increasing availability of effective, evidence-based physical activity
      interventions, widespread diffusion is needed. We examine conceptual foundations
      for research on dissemination and diffusion of physical activity interventions;
      describe two school-based program examples; review examples of dissemination and
      diffusion research on other health behaviors; and examine policies that may
      accelerate the diffusion process. Lack of dissemination and diffusion evaluation
      research and policy advocacy is one of the factors limiting the impact of
      evidence-based physical activity interventions on public health. There is the
      need to collaborate with policy experts from other fields to improve the
      interdisciplinary science base for dissemination and diffusion. The promise of
      widespread adoption of evidence-based physical activity interventions to improve
      public health is sufficient to justify devotion of substantial resources to the
      relevant research on dissemination and diffusion.

PMID- 16979469
TI  - Translating effective clinic-based physical activity interventions into practice.
AB  - An increasing number of studies report on the efficacy of physical activity
      interventions conducted in, or in conjunction with, clinical settings. This
      article reviews the status of the literature with regard to translation to
      practice and describes methods that will heighten the likelihood of translation.
      In general, few physical activity programs have been designed for translation,
      and the diffusion models underlying most reported programs have relied on an
      assumption of linear diffusion into practice. However, recent developments are
      encouraging and examples are provided of programs that utilize relationship or
      systems approaches to translation.

PMID- 16979470
TI  - Dissemination of physical activity evidence, programs, policies, and surveillance
      in the international public health arena.
AB  - The concepts of dissemination can be applied to the international challenges of
      promoting physical activity. With the 2004 release of the World Health
      Organization Global Strategy for Diet and Physical Activity, risk factor
      reduction and noncommunicable disease control are of global health interest. A
      six-step framework is proposed for understanding the attributes of successful
      international dissemination. These include the development of clear and evidence
      based resources or innovations, defining the target audience, selecting
      communication channels, engaging decision makers, and developing evaluation
      frameworks around dissemination. Four case studies to illustrate aspects of the
      framework are presented: (1) learning from dissemination of effective tobacco
      control initiatives, (2) the experience of developing global measures and
      surveillance systems for physical activity, (3) case study of disseminating the
      Agita program-an effective community wide intervention, and (4) disseminating the
      World Health Organization Global Strategy on Diet and Physical Activity.
      Substantial similarities across the experiences described in these case studies
      suggest underlying common themes for international dissemination, but developing
      a stronger evidence base for dissemination efforts remains a research priority.

PMID- 16979471
TI  - Inferring strategies for disseminating physical activity policies, programs, and
      practices from the successes of tobacco control.
AB  - Efforts at reducing tobacco use in the United States and Canada over the last
      half century have been amazingly successful. This article examines those efforts
      in order to identify policies, programs, and practices found useful in tobacco
      control that might be usefully disseminated to world populations to improve rates
      of physical activity. Tobacco-control activities began with efforts to influence
      the individual smoker through public education and counter-advertising.
      Increasing awareness of the addictive properties of tobacco, industry efforts to
      manipulate those properties, and to target youth with aggressive advertising,
      fueled public outrage that supported additional policy changes to include
      community interventions, legal actions, and restraints against the tobacco
      industry. The article first examines ways to view the process of transferring
      knowledge from one enterprise (reducing tobacco consumption) to another
      (increasing physical activity). Several theories of knowledge generalization and
      dissemination are explored: transfer, knowledge utilization, application,
      diffusion, and implementation. The second section identifies the dissemination of
      tobacco control by means of brief health behavior-change interventions for
      smoking cessation that have been successfully integrated into primary clinical
      care. The question of whether similar strategies can be successfully disseminated
      to increase physical activity is examined in detail. The article then moves on to
      look at the success of arguably the most successful program in the world at
      achieving a reduction in tobacco control-the State of California. Finally, we
      compare and contrast some of the lessons as they have played out in another
      national context-Canada. In the concluding section, some lessons are identified
      that we believe may be successfully utilized in societal attempts to increase
      physical activity in world populations.

PMID- 16979472
TI  - Dissemination of physical activity promotion interventions in underserved
      populations.
AB  - Achieving minimum physical activity levels of 30 or more minutes per day will
      require a variety of intervention strategies to engage each segment of an aging
      and increasingly ethnically diverse U.S. population. This article presents a
      focused review of the sparse literature on the diffusion of evidence-based
      physical activity interventions that are culturally appropriate for underserved
      populations. Related literature and experiential insights inform this discussion,
      because so few published studies report outcome data beyond the first diffusion
      phase of intervention development and evaluation. Three brief case studies are
      presented to further illustrate and exemplify key concepts and processes at
      several different stages in diffusing physical activity interventions. Successful
      engagement of underserved populations reflects a delicate balance between
      embracing group customs and values and recognizing the nonmonolithic nature of
      any sociodemographically defined group. The costs of failing to promulgate
      effective physical activity interventions in these groups continue to mount, in
      dollars, health, and lives. Researchers, practitioners, decision makers, and
      policymakers must partner to bridge the evidentiary gap so that the physically
      active lifestyle choices become the easier choices.

PMID- 16979473
TI  - Diffusion and dissemination for increasing physical activity in world
      populations.

PMID- 16979475
TI  - Turning ideas into action.

PMID- 16979477
TI  - Evidence-based therapy: an orthodontic dilemma.

PMID- 16979479
TI  - Nonsurgical correction of Class III malocclusion.

PMID- 16979480
TI  - Bone loss compromises Class III open-bite treatment result.

PMID- 16979481
TI  - The effects of friction and flexural rigidity of the archwire on canine movement
      in sliding mechanics: a numerical simulation with a 3-dimensional finite element
      method.
AB  - INTRODUCTION: The purposes of this article were to clarify the combined effect of
      friction and an archwire's flexural rigidity on canine movement in sliding
      mechanics, and to explain how to select a suitable archwire and force level for
      efficient bodily movement. METHODS: A numerical simulation was carried out by
      using a 3-dimensional finite element method. RESULTS: As the frictional force
      decreased, both the net force acting on and the moving speed of the canine
      increased. The elastic deformation of the archwire increased, and the moving
      pattern of the canine changed from bodily movement to tipping, although there was
      no clearance between the archwire and the bracket slot. When a light wire was
      used, wire deformation increased, and the canine experienced greater tipping.
      These effects of friction and wire properties on canine movement (tipping and
      rotational angles) are combined by using a single parameter, EI/P, where EI is
      the flexural rigidity of the archwire, and P is the net force acting on the
      canine. A suitable combination of EI and P will cause canine bodily movement. The
      EI is determined from the archwire's size and material. CONCLUSIONS: We propose a
      method for estimating a suitable combination in this article.

PMID- 16979482
TI  - Magnetic strength and corrosion of rare earth magnets.
AB  - INTRODUCTION: Rare earth magnets have been used in orthodontics, but their
      corrosion tendency in the oral cavity limits long-term clinical application. The
      aim of this project was to evaluate several; magnet coatings and their effects on
      magnetic flux density. METHODS: A total of 60 neodymium-iron-boron magnets
      divided into 6 equal groups--polytetrafluoroethylene-coated (PTFE), parylene
      coated, and noncoated--were subjected to 4 weeks of aging in saline solution,
      ball milling, and corrosion testing. RESULTS: A significant decrease in magnet
      flux density was recorded after applying a protective layer of parylene, whereas
      a slight decrease was found after applying a protective layer of PTFE. After 4
      weeks of aging, the coated magnets were superior to the noncoated magnets in
      retaining magnetism. The corrosion-behavior test showed no significant difference
      between the 2 types of coated magnets, and considerable amounts of iron-leached
      ions were seen in all groups. CONCLUSIONS: Throughout the processes of coating,
      soaking, ball milling, and corrosion testing, PTFE was a better coating material
      than parylene for preserving magnet flux density. However, corrosion testing
      showed significant metal leaching in all groups.

PMID- 16979483
TI  - Changes in the subgingival microbiota and periodontal parameters before and 3
      months after bracket placement.
AB  - INTRODUCTION: Dental plaque is organized in a biofilm complex that provides
      protection and nutrients for periodontopathic bacteria. Several factors can
      affect microbial colonization, including restorations and orthodontic brackets.
      The aim of this study was to investigate changes in subgingival microbiota and
      clinical parameters before and after bracket placement. METHODS: Clinical
      parameters and subgingival microbial samples were collected from 30 patients
      before and after bracket placement. Thirty additional patients with no
      orthodontic treatment served as controls. Samples were cultured and analyzed for
      periodontopathic and superinfecting bacteria. A descriptive analysis was
      conducted, and chi-square, Student t, Wilcoxon matched, and Mann Whitney rank sum
      tests were used to test for differences between groups (P < or=.05). RESULTS: No
      changes in probing depth or clinical attachment level were observed, but scores
      for bleeding on probing, plaque index, and gingival index increased after bracket
      placement (P < or =.05). Porphyromonas gingivalis, Prevotella
      intermedia/Prevotella nigrescens, Tannerella forsythia, and Fusobacterium species
      were elevated in the experimental group after bracket placement compared with the
      control group (P < or =.01). Superinfecting microorganisms such as Enterobacter
      cloacae, Klebsiella oxytoca, Klebsiella pneumoniae, and Serratia marcescens were
      also found. CONCLUSIONS: Bracket placement influences the accumulation of plaque
      and the colonization of important periodontopathic and superinfecting bacteria,
      resulting in more inflammation and bleeding. Special attention should be paid to
      oral hygiene methods in orthodontic patients.

PMID- 16979484
TI  - The enigma of facial beauty: esthetics, proportions, deformity, and controversy.
AB  - The study of the face and the ability to alter its form have fascinated mankind
      for thousands of years. The clinical ability to alter dentofacial form, whether
      through orthodontics, facial growth modification, or surgery, requires an
      understanding of facial beauty, including the evaluation of facial esthetics,
      proportions, and symmetry. The purposes of this article were to give a brief
      contemporary overview of our concepts of facial beauty and esthetics and to
      consider a long-standing and controversial debate on the treatment of patients
      with dentofacial deformities.

PMID- 16979485
TI  - Methods to evaluate profile preferences for the anteroposterior position of the
      mandible.
AB  - INTRODUCTION: Facial profile disharmonies in the anteroposterior (AP) position of
      the mandible are among the most frequent reasons that patients seek orthodontic
      treatment. Various methods are available for assessing profile preferences, and
      differences between them could affect treatment decisions. The purposes of this
      study were to compare and contrast 3 methods of evaluating profile preferences
      for the AP position of the mandible. METHODS: Facial profile preferences of white
      orthodontists (n = 28) and white (n = 56) and Japanese-American (n = 55)
      laypeople were evaluated. The esthetic significance of variations in the AP
      position of the mandible was investigated by using 3 methods: a traditional
      semantic differential scale, the Perceptometrics method (Health Programs Intl,
      Wellesley, Mass), and the implicit association test (IAT). RESULTS: Findings from
      the semantic differential scale show that, overall, there is a general preference
      among orthodontists and laypeople for an orthognathic profile (P <.001). Findings
      from the Perceptometrics method indicate that orthodontists consider the most
      pleasing profile to be more forward than do lay subjects (P <.001). The IAT
      results show a positive bias among all 3 groups toward orthognathic profiles and
      a negative bias toward profiles with mandibular retrognathism or prognathism. The
      IAT suggested that laypeople were more tolerant of mandibular prognathism in men
      than in women (P <.01), and more tolerant of mandibular retrognathia in white
      women than in men (P = .03). CONCLUSIONS: These results support the benefits of
      using both implicit and explicit methods to assess facial profile preferences.

PMID- 16979486
TI  - Dentofacial features of children with distal occlusions, large overjets, and
      deepbites in the early mixed dentition.
AB  - INTRODUCTION: The aim of this investigation was to analyze craniofacial
      morphology in children with distal bites, large overjets, and deepbites in the
      early mixed dentition. METHODS: The sample comprised 486 Finnish children who are
      participating in an ongoing clinical trial. Cephalograms were obtained at the
      deciduous-mixed dentition interphase for the baseline of the trial. The mean age
      of the children was 5.1 years (SD, 2.6; range, 4.0-7.8 years). RESULTS: Subjects
      with bilateral distal steps of > or =1 mm compared with normal had long midfaces
      (P <.05), short and retrusive mandibles (P <.05), small maxillomandibular
      differentials (P <.001), convex profiles (P <.01), retrusive mandibular incisors
      (P <.01), and large interincisal angles (P <.001). Children with overjets of > or
      =4 mm had retrusive mandibles (P <.001), long maxillae and midfaces (P <.001),
      small maxillomandibular differentials (P <.001), convex profiles (P <.001), and
      protrusive maxillary and retrusive mandibular incisors (P <.001). Children with
      deepbites (overbites of > or =4 mm) had short and retrusive mandibles (P <.05),
      long midfaces (P <.001) and maxillae (P <.05), small maxillomandibular
      differentials (P <.001), convex profiles (P <.01), retrusive mandibular incisors
      (P <.001), and large interincisal angles (P <.001). No differences were found in
      the length of anterior cranial base, the position of maxilla relative to cranial
      base, lower facial height, and facial axis angle between any malocclusion group
      and normal children. All correlations between the occlusal and skeletal
      characteristics were low, suggesting only weak associations at this stage of
      development. CONCLUSIONS: These results indicate that the early dentofacial
      features of children with distal occlusions, large overjets, and deepbites differ
      from normal values. However, the skeletal patterns of these 3 malocclusion types
      showed considerable similarities, with long but neutrally positioned maxillae,
      retrusive mandibles, small maxillomandibular differences, convex profiles,
      retrusive mandibular incisors, and large interincisal angles, but normal growth
      directions and lower facial heights as common features.

PMID- 16979487
TI  - Class III surgical-orthodontic treatment: a cephalometric study.
AB  - INTRODUCTION: In this retrospective study, we investigated treatment outcomes in
      Class III surgical-orthodontic patients. METHODS: Records of 151 consecutively
      completed Class III surgical-orthodontic patients (overjet, 0 mm or less) were
      obtained from 87 consultant orthodontists in the United Kingdom. Pretreatment and
      posttreatment cephalometric radiographs were analyzed. RESULTS: Bimaxillary
      surgical patients (75%) had more negative initial ANB-angle values and smaller
      initial SNA-angle values than those treated with single-jaw mandibular surgery.
      Mandibular surgery patients (15%) had greater pretreatment mandibular prominence
      (SNB angle) than maxillary patients. Maxilla-only patients (10%) had lower
      negative initial overjet values than bimaxillary patients. An overjet within the
      ideal range of 1 to 4 mm was achieved in 83% of the patients. Logistic regression
      identified no predictors of ideal overjet outcome. SNB angle was corrected to
      within the ideal range of 75 degrees to 81 degrees in 44% of the patients. This
      was less likely in those treated with maxillary surgery only and larger initial
      SNB-angle values. An ideal posttreatment ANB angle (1 degrees to 5 degrees) was
      achieved in 40% of the patients and was more likely in those with bimaxillary
      surgery, lower negative pretreatment ANB angles, and presurgical orthodontic
      extractions in the maxillary arch. Ideal posttreatment unadjusted Holdaway angles
      (7 degrees to 14 degrees) were achieved in 59% of the patients and were more
      likely when single-jaw mandibular surgery was used. Incisor decompensation was
      incomplete in 46% of the patients and was associated with mandibular arch
      extractions. CONCLUSIONS: Surgical-orthodontic treatment had a high success rate
      in normalizing the overjet and soft-tissue profile to within ideal ranges in
      Class III patients. Bimaxillary surgery was the most frequently used procedure
      and was associated with an increased likelihood of an ideal correction of the
      anteroposterior skeletal discrepancy.

PMID- 16979488
TI  - One-year postoperative stability of LeFort I osteotomies with biodegradable
      fixation: a retrospective analysis of skeletal relapse.
AB  - INTRODUCTION: The purpose of this retrospective analysis was to determine the
      magnitude of postoperative skeletal relapse of a maxillary LeFort I osteotomy
      procedure performed with fixation plates and screws composed of a biodegradable
      copolymer (poly-L lactic and poly-L glycolic acid). METHODS: Twenty-three
      consecutively treated subjects, aged 19 to 39, were diagnosed with excess
      vertical maxillary height or anteroposterior maxillary deficiency and treated
      with LeFort I impaction or advancement osteotomies. Lateral cephalometric
      radiographs were measured and compared for the absolute magnitude of skeletal
      relapse from pretreatment to immediately postoperative to 1 year after surgery.
      RESULTS: Correlation analysis determined that a positive relationship existed
      between the magnitude of the surgical movement and the magnitude of postoperative
      relapse. The greatest relapse for any subject in any direction was 0.940 mm
      (anterior nasal spine to nasion-perpendicular). The greatest average relapses
      were 0.249 mm horizontally (anterior nasal spine to Frankfort horizontal) and
      0.141 mm vertically (M-point Frankfort horizontal). CONCLUSIONS: The most
      significant contribution of this study to surgical stability literature is
      reporting the absolute magnitudes of postoperative relapse over a 1-year period
      of observation. Consistent with previously published reports on postoperative
      stability, greater magnitudes of relapse were noted for larger surgical
      movements, yet the absolute values of postoperative relapse with biodegradable
      copolymers was clinically negligible. Biodegradable copolymers can provide
      excellent postoperative stability for superior and anterior maxillary surgical
      repositioning that appears to rival published stability measurements for rigid
      internal metallic fixation.

PMID- 16979489
TI  - Extreme variations in the shape of mandibular premolars.
AB  - INTRODUCTION: Human mandibular premolars (MnP) are highly variable in shape. An
      extreme variation, called here MnP tooth-shape deviation (MnP-TSD), is
      characterized by a squeezed faciolingual (FL) dimension and an enlarged
      mesiodistal (MD) dimension, reversing the typical premolar proportions. This is
      the first in-depth study of the MnP-TSD anomaly. METHODS: Eighteen subjects with
      29 MnP-TSD teeth were selected for odontometric analysis by using dental casts.
      For each affected MnP, an MD/FL proportional index and a representation of crown
      area (MD x FL) were calculated from maximum MD and FL crown diameters. Data were
      compared with reference values for MnP. RESULTS: MnP-TSD was observed over 8
      times more frequently in second premolars than in first premolars. Male
      expression was slightly greater (ratio, 1.4:1), and bilateral occurrence was
      observed in 59% of the subjects. Occurrence was noted among all ethno-racial
      groupings in the sample (16 whites, 1 black, 1 Asian). The MD/FL index of
      premolars with the MnP-TSD anomaly always exceeded 100 (103 to 148); this is
      significantly higher than normal values. In contrast, the crown areas of the
      affected teeth were remarkably similar to normal reference values. In addition to
      the squeezed tooth shape, subjects with pronounced MnP-TSD also had
      mesiolingual/distofacial twisting in MnP occlusal features. CONCLUSIONS:
      Extremely abnormal MD/FL proportions coupled with normal crown-area values
      provide reliable factors for differential diagnosis of the MnP-TSD anomaly. This
      uncommon MnP dysmorphology can be a challenge to orthodontic movement and
      achievement of ideal occlusal intercuspation.

PMID- 16979490
TI  - Longitudinal study of temporomandibular joint disc status and craniofacial
      growth.
AB  - INTRODUCTION: The objective of this retrospective cohort study was to assess the
      association of temporomandibular joint (TMJ) disc status and craniofacial growth.
      METHODS: Seventy-nine subjects (52 female, 27 male) with and without TMJ disc
      abnormalities were followed for a mean time of 3 years 8 months. Of this sample,
      40 subjects (21 female, 19 male) received orthodontic treatment. Disc
      displacement and disc length measurements from magnetic resonance imaging of the
      jaw joints were used to evaluate TMJ disc status. A principal component analysis
      was used to produce a single disc status score per subject. Horizontal and
      vertical growth changes were obtained from cephalometric radiographs. The Fishman
      skeletal maturation index system was used to obtain the percentage of the total
      craniofacial growth attained. In addition, previous orthodontic treatment and
      time frames between the follow-up cephalometric radiographs were considered.
      RESULTS: A stepwise multiple linear regression analysis was used to evaluate the
      influence of TMJ disc status and orthodontic treatment on the displacement
      vectors between initial records (T1) and final records (T2) for each
      cephalometric point. Less horizontal and vertical growth was found in specific
      regions of the maxilla and the mandible in subjects with TMJ disc abnormalities,
      although their respective determination coefficients were mild (R2 <11.2%).
      CONCLUSIONS: TMJ disc abnormality was associated with reduced forward growth of
      the maxillary and mandibular bodies. TMJ disc abnormality was associated with
      reduced downward growth of the mandibular ramus.

PMID- 16979492
TI  - A comparison of scanned lateral cephalograms with corresponding original
      radiographs.
AB  - INTRODUCTION: Digital cephalometric radiography is gaining popularity in
      orthodontic practices. However, few studies have compared measurements and
      superimpositions on analog radiographs with those made on scanned digital images.
      The objectives of this study were to evaluate distortion associated with scanning
      lateral cephalograms and printing to hard copy, and to assess the accuracy of
      digital images for regular cephalometric tasks. METHODS: Pretreatment and
      posttreatment cephalograms from 30 subjects were selected and 3 groups were
      created: original, digital, and hard copy. All films had 8 fiducial marks punched
      and were scanned at 150 dots per inch. The hard copies were created with a laser
      printer. Twenty-three cephalometric measures and 3 superimpositions were
      evaluated for distortion, measurement accuracy, and superimposition results.
      Paired t tests were used to assess statistical significance. RESULTS: Distortion
      between the original and the scanned image showed 0.8 mm vertical enlargement and
      0.4 mm horizontal reduction. Printed radiographs had 1.1 mm vertical and 0.4 mm
      horizontal enlargement. All differences were statistically significant.
      Cephalometric comparisons between original and digital images showed statistical
      differences in Frankfort horizontal (FH)-occlusal plane, maxillary central
      incisor-FH, facial plane, y-axis, Frankfort plane to mandibular plane angle
      (FMA), and FH-Naison to point A (NA). Significant differences also were found in
      facial plane, y-axis, FMA, and FH-NA when comparing the digital and the hard-copy
      images. All measurements with differences contained the landmarks porion and
      orbitale. No differences were found between the original and the hard-copy
      images. Likewise, no significant differences were found between the original and
      the digital superimpositions. CONCLUSIONS: Although some distortion was found,
      the relatively small horizontal and vertical discrepancies were deemed clinically
      insignificant. Landmark identification errors on scanned images contributed to
      the discrepancies in cephalometric analysis. Therefore, for clinical orthodontic
      applications, scanned cephalograms can be used. However, caution must be
      exercised when determining porion and orbitale.

PMID- 16979491
TI  - Discrimination of internal derangement of temporomandibular joint by lateral
      cephalometric analysis.
AB  - INTRODUCTION: The purposes of this study were to analyze the progress of internal
      derangement (ID) of the temporomandibular joint (TMJ) and to find critical
      yardsticks that can be used during lateral cephalometric analysis to identify
      subjects with potential ID. METHODS: The sample consisted of 134 women whose
      primary complaints were malocclusions. They were divided into 5 groups based on
      the results of magnetic resonance imaging of bilateral TMJs: bilateral normal
      disc position, unilateral disc displacement with reduction (DDR) and
      contralateral normal disc position, bilateral DDR, unilateral DDR and
      contralateral disc displacement without reduction (DDNR), and bilateral DDNR.
      Thirty-six cephalometric variables from their lateral cephalograms were analyzed
      with 1-way ANOVA and discriminant analysis to determine the key factors in
      identifying subjects with TMJ ID. RESULTS: Backward positioning of the mandible,
      clockwise rotation of the mandible, proclination of the mandibular incisors, and
      increase in overjet intensified gradually with the progression of TMJ ID, and the
      subjects with bilateral DDNR showed the greatest changes in dentofacial
      morphology. Stepwise variable selection in discriminant analysis identified the
      following 2 variables: mandibular incisor to Frankfort horizontal plane angle and
      overjet. Discriminant analysis resulted in the correct classification of 79.1% of
      the subjects and showed that those with smaller mandibular incisor to Frankfort
      horizontal plane angles and larger overjets had high possibilities of TMJ ID.
      CONCLUSIONS: This study suggests that some cephalometric variables can be used as
      an auxiliary diagnostic tool to help identify patients with potential TMJ ID.

PMID- 16979493
TI  - Factors associated with the duration of forced eruption of impacted maxillary
      canines: a retrospective study.
AB  - INTRODUCTION: More information is needed to better predict the duration, cost,
      success rate, and incidence of complications when treating impacted maxillary
      canines. The aim of this study was to identify factors that affect the number of
      visits required to complete the canine forced eruption phase. METHODS: Data from
      diagnostic and treatment notes and radiographs of 87 consecutive adult and
      adolescent patients were analyzed by stepwise regression analysis. RESULTS: The
      results indicated a strong direct correlation of the number of visits with the
      patient's age (P < .0001), the distance between the canine cusp tip and the
      occlusal plane (P <.0001), and the zone (P = .0058); mesially located cusps
      required more visits. A weaker inverse correlation was found with the beta angle
      (P = .0289), that is, and the angle between the canine and lateral incisor axes.
      No significant correlation was found with other variables, including sex and
      several linear and angular measurements made on panoramic and sagittal
      radiographs. CONCLUSIONS: Age, distance from the canine cusp tip to the occlusal
      plane, zone, and beta angle appear to provide a rather accurate estimate (R2 =
      0.42) of the number of visits needed to complete the forced eruption phase. This
      information allows for a prediction that might be sufficient to give the patient
      correct information and to estimate the final cost of the treatment.

PMID- 16979494
TI  - In-vivo effects of fluoridated antiplaque dentifrice and bonding material on
      enamel demineralization adjacent to orthodontic appliances.
AB  - INTRODUCTION: The effect of a fluoridated antiplaque dentifrice on the
      development of caries lesions adjacent to dental appliances bonded with ionomeric
      material is unknown. METHODS: Fourteen orthodontic patients were randomly divided
      into 2 groups of 7. One group brushed 3 times a day with a fluoridated
      dentifrice, and the other used an experimental antiplaque fluoridated
      formulation. Bracket bases were randomly bonded with either resin-modified glass
      ionomer cement or composite resin to the buccal surfaces of either the maxillary
      left or right premolars in each subject. The teeth were banded, leaving a space
      on the buccal surface to allow dental plaque accumulation. After 28 days of
      dentifrice use, the teeth were extracted, and mineral loss in the enamel adjacent
      to the bonded material was assessed by cross-sectional microhardness. RESULTS:
      Mineral loss in the enamel surrounding the bond with the resin-modified glass
      ionomer cement was lower (P <.05) than around the composite bond. Enamel
      demineralization was lower (P <.05) in subjects who used the experimental
      antiplaque fluoridated formulation than in those who used the fluoridated one.
      CONCLUSIONS: The data suggest that an antiplaque fluoridated dentifrice is
      superior to one that is only fluoridated for reducing enamel demineralization
      adjacent to dental material bonded with composite, but the effect seems
      irrelevant when bonding is done with the ionomeric material.

PMID- 16979495
TI  - Aspirin, acetaminophen, and ibuprofen: their effects on orthodontic tooth
      movement.
AB  - INTRODUCTION: Orthodontic patients often take analgesics for pain during
      treatment. But various analgesics have different capacities to inhibit
      prostaglandins, and these differences might affect tooth movement. The purposes
      of this study were to determine by direct measurement the effects that
      acetylsalicylic acid, ibuprofen, and acetaminophen have on orthodontic tooth
      movement in rats and to evaluate histologically the differences in bone
      resorption in the pressure area in rats treated with these analgesics. METHODS:
      Thirty-six adult male Wistar rats were divided in 4 groups of 9 each. Orthodontic
      appliances were placed on the rats' incisors. In the 3 experimental groups,
      analgesics were diluted in reverse osmosis water and delivered via a gastric
      tube: 100 mg/kg acetylsalicylic acid, or 30 mg/kg ibuprofen, or 200 mg/kg
      acetaminophen. Control animals received only the reverse osmosis water. At the
      end of the experimental period, the rats were killed and histological
      examinations were performed. RESULTS: Analysis of variance showed statistically
      significant differences between the control group, which was given reverse
      osmosis water, and the groups given aspirin and ibuprofen. There were also
      statistically significant differences between the acetaminophen group and the
      ibuprofen and aspirin groups, respectively. There was no significant difference
      between the acetaminophen group and the control group, or between the aspirin and
      ibuprofen groups. Tooth movement was similar in the groups. CONCLUSIONS: The
      results indicate that nonsteroidal anti-inflammatory analgesics such as aspirin
      and ibuprofen diminish the number of osteoclasts, probably by inhibiting the
      secretion of prostaglandins, thereby reducing orthodontic tooth movement.
      Acetaminophen did not affect orthodontic tooth movement in rats, and it might be
      the analgesic of choice for treating pain associated with orthodontic treatment.

PMID- 16979496
TI  - Pain relief by single low-level laser irradiation in orthodontic patients
      undergoing fixed appliance therapy.
AB  - INTRODUCTION: The objective of this study was to analyze the effect of single low
      level laser therapy (LLLT) irradiation on pain perception in patients having
      fixed appliance treatment. METHODS: Seventy-six patients (46 women, 30 men; mean
      age, 23.1 years) enrolled in this single-blind study were assigned to 2 groups.
      The patients in group 1 (G1; 38 patients, 13 men, 25 women; mean age, 25.1 years)
      received a single course of LLLT (Mini Laser 2075, Helbo Photodynamic Systems
      GmbH & Co KG, Linz, Austria; wavelength 670 nm, power output 75 mW) for 30
      seconds per banded tooth. The patients in group 2 (G2; 38 patients, 17 men, 21
      women; mean age, 21.0 years) received placebo laser therapy without active laser
      irradiation. Pain perception was evaluated at 6, 30, and 54 hours after LLLT by
      self-rating with a standardized questionnaire. RESULTS: Major differences in pain
      perception were found between the 2 groups. The number of patients reporting pain
      at 6 hours was significantly lower in G1 (n = 14) than in G2 (n = 29) (P <.05),
      and the differences persisted at 30 hours (G1, n = 22; G2, n = 33) (P <.05). At
      54 hours, no significant differences were seen between the number of patients
      reporting pain (G1, n = 20; G2, n = 25), although the women had a different
      prevalence between G1 (n = 11) and G2 (n = 15) (P = .079). At 6, 30, and 54
      hours, more than 90% of the subjects in both groups described the pain as
      "tearing." CONCLUSIONS: LLLT immediately after multibanding reduced the
      prevalence of pain perception at 6 and 30 hours. LLLT might have positive effects
      in orthodontic patients not only immediately after multibanding, but also for
      preventing pain during treatment.

PMID- 16979497
TI  - Effective single-charge end point of cordless light-emitting diode light-curing
      units.
AB  - INTRODUCTION: The purpose of this study was to evaluate the battery lives of
      cordless light-emitting diodes (LEDs) and their effect on orthodontic bracket
      bond strength. METHODS: One hundred eighty-six metal orthodontic brackets were
      bonded to extracted molars. Two LED light-curing units (L. E. Demetron [SDS/Kerr,
      Orange, Calif] and Ortholux [3M Unitek, Monrovia, Calif]) were evaluated. Each
      light was used to bond 93 specimens. One bracket was bonded every 5 minutes until
      the battery ran out. The lights were activated for 20 seconds, then automatically
      turned off for 40 seconds every minute (33% duty cycle) without recharging.
      Bonded specimens were stored in water at 37 degrees C for 24 hours and then
      subjected to shear force with a universal testing machine until bracket failure.
      RESULTS: Repeated measures ANOVA detected significantly weaker mean shear bond
      strength and fewer consecutive cures with the Ortholux compared with the L. E.
      Demetron light-curing unit. However, when the first 5 time points were excluded,
      there were no differences between the 2 lights, demonstrating that the lights
      performed similarly after the first 20 minutes of operation Just before battery
      failure, both lights still provided the same power density as at the beginning.
      CONCLUSIONS: Both light-curing units provided adequate power density for up to 2
      hours without recharging at a 33% duty cycle. There was no significant decrease
      in power in cordless LED light-curing units as the battery life approached its
      end point.

PMID- 16979498
TI  - Comparison of wire loop and shear blade as the 2 most common methods for testing
      orthodontic shear bond strength.
AB  - INTRODUCTION: The purpose of this study was to compare 2 common methods of
      measuring orthodontic shear bond strength. METHODS: Brackets were bonded to 40
      bovine incisors, and the teeth were mounted in a jig. The teeth were paired for
      symmetry, and the pairs were divided into 2 groups for debonding. In group 1, the
      shear force was applied with a rectangular wire under the tie wings. In group 2,
      a shearing blade applied force to the junction between the bracket base and the
      adhesive. RESULTS: Debonding with the shear blade produced higher (24.86 +/- 7.44
      MPa) and more dispersed (coefficient of variation = 29.91%) bond strengths
      compared with the wire loop (17.12 +/- 3.16 MPa, coefficient of variation =
      18.44%). Adhesive remnant index (ARI) scores showed a tendency for cohesive
      failure in the enamel in the shear-blade group (ARI = 5) compared with adhesive
      failure (ARI = 3) in the wire group. CONCLUSIONS: There is a need to standardize
      bond strength tests. The results of this study favor the wire-loop method, which
      might have more similarity to clinical loads. The regression formula might make
      comparison of previous studies easier.

PMID- 16979499
TI  - Acromegaly in an orthodontic patient.
AB  - A 32-year-old white man presented for orthodontic treatment with the chief
      complaint of mandibular prognathism; he was later found to have acromegaly.
      General information about pituitary adenomas, specifically growth hormone
      adenomas, is given, and treatment options are discussed.

PMID- 16979500
TI  - Nonextraction treatment of an open bite with microscrew implant anchorage.
AB  - A 16-year-old girl with an anterior open bite was treated with nonextraction
      therapy that included intrusion of the maxillary and mandibular posterior teeth
      with microscrew implants. Implants (diameter, 1.2 mm; length, 8 or 6 mm) were
      placed into alveolar bone near the posterior teeth and used as anchorage for
      intrusive force. To prevent adverse side effects of buccoversion or linguoversion
      of the posterior teeth during intrusion, a transpalatal bar and a lingual arch
      were placed. The 3-mm anterior open bite was corrected in 11 months of treatment,
      after intrusion of the maxillary and mandibular posterior teeth and autorotation
      of the mandible. The posterior intrusion relapsed in the early stage of
      retention, at 8 months; thereafter, no obvious relapse was evident in the
      vertical position of the molars and the FMA. The treatment mechanics of anterior
      open bite with posterior intrusion by using microscrew implants were effective
      but still require a proper retention protocol.

PMID- 16979501
TI  - Category 7: anteroposterior skeletal discrepency.
AB  - This case report was part of a display of cases sponsored by the American Board
      of Orthodontics at the AAO annual session in San Francisco, May 2005. The summary
      of treatment and records are reprinted here much as they were submitted to the
      board.

PMID- 16979502
TI  - Three-dimensional cephalometry: spiral multi-slice vs cone-beam computed
      tomography.
AB  - Three-dimensional (3D) craniofacial imaging techniques are becoming increasingly
      popular and have opened new possibilities for orthodontic assessment, treatment,
      and follow-up. Recently, a new 3D cephalometric method based on spiral multi
      slice (MS) computed tomography (CT) was developed and validated by our research
      group. This innovative 3D virtual approach is a bridge between conventional
      cephalometry and modern craniofacial imaging techniques and provides high
      quality, accurate, and reliable quantitative 3D data. The aim of this article was
      to describe the advantages and the disadvantages of spiral MS-CT 3D cephalometry
      and to discuss the potential of cone-beam CT 3D cephalometry.

PMID- 16979503
TI  - Litigation, legislation, and ethics. The admissibility of digital images.

PMID- 16979507
TI  - Studying nuclear protein import in yeast.
AB  - The yeast Saccharomyces cerevisiae is a common model organism for biological
      discovery. It has become popularized primarily because it is biochemically and
      genetically amenable for many fundamental studies on eukaryotic cells. These
      features, as well as the development of a number of procedures and reagents for
      isolating protein complexes, and for following macromolecules in vivo, have also
      fueled studies on nucleo-cytoplasmic transport in yeast. One limitation of using
      yeast to study transport has been the absence of a reconstituted in vitro system
      that yields quantitative data. However, advances in microscopy and data analysis
      have recently enabled quantitative nuclear import studies, which, when coupled
      with the significant advantages of yeast, promise to yield new fundamental
      insights into the mechanisms of nucleo-cytoplasmic transport.

PMID- 16979508
TI  - Health care myopia: getting patient access to care back in focus.

PMID- 16979509
TI  - HIV vaccine research and the search for hope: a reflection from Women's History
      Month.

PMID- 16979510
TI  - Methamphetamine use and HIV symptom self-management.
AB  - This study describes HIV-related symptoms in a methamphetamine-using sample of 20
      men living in southern California. Data were obtained in 2004 and 2005 using a
      cross-sectional design. Participants were administered the Revised Sign and
      Symptom Check-List for Persons With HIV Disease and the Addiction Severity Index
      and were engaged in a semistructured interview. Participants reported using
      methamphetamine to treat HIV-related depression, fatigue, and neuropathic pain.
      HIV-related diarrhea seemed to diminish with methamphetamine use, although this
      was not a motivation for use. These results, although preliminary, suggest that
      further study of the interplay between methamphetamine use and HIV symptom
      management is warranted.

PMID- 16979511
TI  - Effects of ice massage on neuropathic pain in persons with AIDS.
AB  - Peripheral neuropathic pain is a unique form of chronic pain that afflicts up to
      50% of persons with AIDS. The purpose of this pilot study was to examine the
      effects of ice massage to reduce neuropathic pain and improve sleep quality and
      to determine the feasibility of a larger study. A repeated measures design was
      used. The three treatments consisted of ice massage, dry-towel massage, and
      presence. Consecutive sampling was used to select 33 persons with AIDS who had
      neuropathic pain. Although the results of the study were negative, there was a
      decrease in pain intensity over time with both the ice massage and towel massage,
      suggesting that the intervention has some clinical benefit.

PMID- 16979512
TI  - Sensation seeking, self-esteem, and unprotected sex in college students.
AB  - This descriptive correlational study examined the relationships of sexual
      sensation seeking, self-esteem, and self-efficacy in condom use, stages of
      change, and alcohol consumption to HIV risk-taking behaviors among college
      students. A total of 159 students completed an online survey in 2004. Instruments
      included the Sexual Sensation Seeking Scale, College Alcohol Problems Scale,
      Condom Use Scale, and Rosenberg Self-Esteem Scale. High sensation seekers had
      higher self-esteem, more self-efficacy in condom usage, fewer problems associated
      with alcohol consumption, and belonged to Greek organizations (F [1,158] = 12.54;
      p < .0005). Women who were high sensation seekers perceived more advantages (F
      [1, 116] = 1.67; p = .05) than disadvantages (F [1, 116] = 2.01; p = .01) to
      using condoms. Men consumed significantly more alcohol and had more social
      problems related to alcohol use than women (F [1, 158] = 5.04; p < .03). Students
      in Greek organizations had significantly more positive attitudes (X(2) [1] =
      4.55; p < .03) and more respect for themselves (X(2) [1] = 11.22; p < .0008) than
      other students and were more likely to be tested for HIV (X(2) [1] = 3.85; p <
      .05). Students with low self-esteem consumed more alcohol, had more sexual
      partners, and had more HIV risk-taking behaviors than other students. Even though
      students were reported to be efficacious in condom usage, they used them
      inconsistently with their sexual partners and were in the earlier stages of
      change. Interventions are needed in the community to help sexually active
      individuals take responsibility for their sexual health and to increase the
      awareness of the need to be tested for HIV.

PMID- 16979513
TI  - Symbolic interactionism in grounded theory studies: women surviving with HIV/AIDS
      in rural northern Thailand.
AB  - Although it is generally acknowledged that symbolic interactionism and grounded
      theory are connected, the precise nature of their connection remains implicit and
      unexplained. As a result, many grounded theory studies are undertaken without an
      explanatory framework. This in turn results in the description rather than the
      explanation of data determined. In this report, the authors make explicit and
      explain the nature of the connections between symbolic interactionism and
      grounded theory research. Specifically, they make explicit the connection between
      Blumer's methodological principles and processes and grounded theory methodology.
      In addition, the authors illustrate the explanatory power of symbolic
      interactionism in grounded theory using data from a study of the HIV/AIDS
      experiences of married and widowed Thai women.

PMID- 16979514
TI  - Risk behavior, perceptions of HIV risk, and risk-reduction behavior among a small
      group of rural African American women who use drugs.
AB  - HIV/AIDS is a health crisis for African Americans. African American women are
      exposed to HIV primarily through sexual behavior, which is an increased risk for
      women who use drugs. The study design was a mixed method consisting of an
      ethnography with ongoing participant observation and in-depth interviews and a
      questionnaire. The purpose of the questionnaire component was to explore drug
      use, sexual behavior, health history, and perceptions. The questionnaire was
      administered at months 6 and 18. Data for this report were derived from the first
      questionnaire with 30 respondents. The majority of respondents (82.7%) used
      polysubstances consisting of cocaine, marijuana, and alcohol. Between 33% and 50%
      exchanged sex for drugs or money, with less than half ever using condoms. About
      37% perceived that they had no risk of acquiring HIV, whereas 52% perceived a 25%
      chance. The pattern of HIV testing in which 33% of the women were tested 10 times
      or more was unexpected because of the low perception of risk. The principal
      conclusion was that there is great need to intervene with prevention efforts
      targeting rural women who use drugs in an attempt to curb increasing rates of
      sexually transmitted infections including HIV.

PMID- 16979515
TI  - Juxtatumoral desmoplastic stromal reaction is associated with high tumor cell
      dissociation in squamous cell carcinomas of the uterine cervix.
AB  - There are different types of tumoral growth patterns invading host tissue. During
      tumor infiltration, cancer cells not only destroy the pre-existing extracellular
      matrix, but usually induce new matrix formation by activating the peritumoral
      stromal cells; that is, desmoplastic stromal reaction (DSR) at the front of
      invasion (juxtatumoral stroma). This study evaluates the association between
      different types of invasion and DSR. Eighty-eight squamous cell carcinomas
      (Federation Internationale de Gynecologie et d'Obstetrique [FIGO] stage IB to IV)
      were evaluated histologically for different patterns of invasion (PI) using a 3
      level scoring system (pushing, finger-like, and spray-like). Desmoplastic stromal
      reaction was scored from none to weak, moderate, or strong. The pattern of
      invasion and DSR were compared with patients' age, FIGO stage, clinical tumor
      size, tumor grade, and the presence of lymphovascular space involvement. Finger
      like PI was the most common (72.7%), followed by the spray-like PI (27.3%),
      whereas pushing PI was not seen. Of the tumors, 23.9% showed no DSR; 51.1%, weak;
      14.8%, moderate; and 10.2%, strong DSR. Tumors with spray-like PI showed a
      significantly stronger desmoplastic reaction compared with the finger-like PI (P
      < .0001) and were significantly associated with poor tumor cell differentiation
      (P = .018). Moderate or strong DSR was associated with G2 and G3 carcinomas (P =
      .027). No correlation was seen neither for PI and DSR to lymphovascular space
      involvement, FIGO stage, and tumor size. The intensity of DSR, as understood in
      the context of a remodeling of the juxtatumoral stroma to the infiltrative tumor
      growth, might be indicative of a highly dissociative tumor growth and is
      correlated to poorly differentiated tumors.

PMID- 16979516
TI  - Lipofuscin pigment can be used as a prognostic marker in prostatic
      adenocarcinoma.
AB  - Lipofuscin, known as the "wear and tear" pigment, is seen in cells undergoing
      regressive changes, the seminal vesicles and the ejaculatory ducts. It is also
      present in prostatic adenocarcinoma. The purpose of this study is to evaluate the
      prognostic significance of lipofuscin in prostatic adenocarcinoma. Lipofuscin was
      evaluated in 736 hematoxylin-eosin-stained slides from 60 conventional and whole
      mounted consecutive radical prostatectomies from December 1996 to February 2002.
      The adenocarcinoma cases were divided into lipofuscin-positive group and
      lipofuscin-negative group. The Gleason score and pathologic stage were compared
      between the 2 groups. Percentage of cells positive for p53 and MIB-1 was also
      compared. Lipofuscin pigment was found in 17 (31%) of 60 prostatic
      adenocarcinomas as random, sparse, fine, yellow-brown intracytoplasmic granules
      staining positive for cathepsin D and negative for S-100 protein. Using logistic
      regression to exclude age as a confounding factor, lower Gleason scores and
      pathologic stages were demonstrated in the lipofuscin-positive group. There was
      also a significant difference between the 2 groups in tumor volume, degree of
      capsular invasion, and positive margins. The difference in seminal vesicle
      invasion and vascular invasion between the 2 groups was not statistically
      significant. Lipofuscin in prostatic adenocarcinoma correlates with both lower
      Gleason score and pathologic stage. Lipofuscin probably indicates slow cellular
      turnover as suggested by the low proliferation rate and p53 expression. The value
      of lipofuscin in biopsy as a predictor separating aggressive from indolent
      disease needs further investigation.

PMID- 16979517
TI  - Primary plasma cell leukemia: morphologic, immunophenotypic, and cytogenetic
      features of 4 cases treated with chemotherapy and stem cell transplantation.
AB  - Plasma cell leukemia (PCL) is a neoplastic disorder of plasma cells of which
      there are 2 forms, primary PCL and secondary PCL, the latter occurring in
      patients with a history of plasma cell myeloma. We describe 4 patients with
      primary PCL. In all cases, the bone marrow aspirate smears and biopsy specimens
      demonstrated a diffuse infiltrate of atypical plasma cells that were difficult to
      classify using morphologic criteria alone. Immunophenotypic studies showed that
      each case was positive for plasma cell-associated antigens (cytoplasmic
      immunoglobin, CD38, or CD138) and negative for CD20. Of 4 cases, 3 had complex
      karyotypes, including the t(11;14)(q13;q32) or del(11)(q13). Despite chemotherapy
      and the use of novel therapeutic agents and stem cell transplantation, all 4
      patients had short survival.

PMID- 16979518
TI  - Immunohistochemical detection of p63 in testicular germ cell neoplasia.
AB  - p63 is a novel transcription factor-encoding gene with sequence homology to p53.
      p63 proteins have epithelial stem-cell regulatory functions and play a critical
      role in tissue development. Study of p63 expression in testicular germ cell
      tumors has been limited. Thirty-four archival cases of testicular germ cell
      neoplasia were examined and stained with monoclonal anti-p63 antibody 4A4 using
      standard methods. Included were 19 seminomas, 1 pure teratoma, 3 pure embryonal
      carcinomas, 1 pure yolk sac tumor, and 10 mixed germ cell tumors. p63 staining
      was consistently positive in teratomas in areas of squamous differentiation and
      in basal reserve-like cells in foci of respiratory/endodermal differentiation.
      Strong p63 staining was observed within cytotrophoblasts of choriocarcinoma
      (1/1), whereas focal positivity was detected in embryonal carcinomas (4/10) and
      yolk sac tumors (2/5). Seminomas and intratubular germ cell neoplasia were p63
      negative. These findings may suggest the presence of pluripotent p63-positive
      stem cell-like nests in yolk sac tumors and embryonal carcinomas or may represent
      areas of an occult teratoma phenotype undetectable histopathologically on
      hemotoxylin-eosin sections. p63 positivity in cytotrophoblasts of choriocarcinoma
      is consistent with gynecologic studies, possibly reflecting the role of p63 in
      the oncogenesis of neoplastic trophoblasts. The consistent p63 negativity in
      seminomas may reflect a precommitted embryonic precursor-like phenotype.

PMID- 16979519
TI  - Histopathologic changes in human true vocal folds: a postmortem study.
AB  - Several articles describe the gross pathology alterations of the true vocal cords
      (TVC), but the histopathology descriptions in adults are rare in the literature
      and are normally associated with neoplasia. The aim of this study is to identify
      the TVC morphological lesions in adult autopsies. This was a cross-sectional
      study of 266 adults' larynxes consecutively autopsied from 1993 to 2003.
      Histochemical and immunohistochemical methods were used for morphological
      analysis. Considering the morphological analysis, 97 TVC (36.5%) were considered
      normal. The following lesions were found in the TVC: thickening of the basal
      membrane of the TVC in 81 patients (30.5%), inflammatory reaction in 66 patients
      (24.8%), hemorrhage in 19 patients (7.1%), and ulceration in 3 patients (1.1%).
      Our study demonstrated that the TVC microscopic lesions are frequent, present
      different morphological patterns, and showed different causes from what had been
      described until nowadays by the literature. Despite this difference in the
      morphological pattern, we were able to identify a common lesion pathway for
      ethiological different diseases.

PMID- 16979520
TI  - Parosteal lipoma of the thigh with cartilaginous and osseous differentiation: an
      osteochondrolipoma.
AB  - Lipomas are very common benign soft tissue neoplasms. They are usually slow
      growing and may occur anywhere in the body. Mature cartilage and bone arising in
      a lipoma is a rare event and is mostly associated with a parosteal localization
      of the neoplasm. We describe a new case of osteochondrolipoma showing not only
      major adipocytic differentiation but also areas of fibrocytic and cartilaginous
      cell differentiation and bone formation (both endochondral and membranous). The
      occurrence of at least 4 distinct directions of mesenchymal cell differentiation
      within a benign neoplasia underlines the concept of multilineage differentiation
      of pluripotent mesenchymal stem cells. Such a multidirectional potential was
      recently well established in vitro in stem cells present in adult adipocytic
      tissue.

PMID- 16979521
TI  - Myxopapillary ependymoma of the posterior mediastinum.
AB  - A left paravertebral mass discovered incidentally on routine examination in a 39
      year-old woman is described. Computerized tomography studies revealed a 7 x 6 cm,
      well circumscribed, noncalcified soft tissue mass with lobular borders abutting
      the left inferior pulmonary vein and descending aorta. It was not possible to
      determine the exact anatomic location of the mass based on the imaging studies as
      both peripheral lung tumors and posterior mediastinal lesions may exhibit the
      imaging findings described here. At thoracotomy, the mass was seen to be well
      circumscribed, focally attached to the pleura but without involvement of lung
      parenchyma, and situated in the left posterior mediastinum. On histological
      examination, the lesion showed the classical features of myxopapillary
      ependymoma. Immunohistochemical studies confirmed this impression by
      demonstrating strong positivity of the tumor cells for S-100 protein, glial
      fibrillary acidic protein, and CD99 and negative staining with other
      differentiation markers. A review of the literature with a discussion of the
      histologic and radiologic differential diagnosis of these lesions is presented.

PMID- 16979522
TI  - Ovarian Sertoli-Leydig cell tumor of intermediate grade with heterologous
      elements of rhabdomyosarcoma. A case report and a review of the literature.
AB  - Ovarian Sertoli-Leydig cell tumors (SLCTs) are rare sex cord-stromal tumors, and
      among them, tumors with heterologous mesenchymal elements are exceptional and
      mainly associated with poorly differentiated tumors and are often fatal. We
      present the fourth case of an ovarian SLCT of intermediate differentiation with
      rhabdomyosarcoma and a review of the literature. Surgical treatment was
      conservative with preservation of the contralateral adnexa and uterus. No
      adjuvant treatment was given. At 4 years control post surgery, the patient was
      without evidence of disease. Extensive sampling of SLCTs is important because
      heterologous elements may be sparse. Immature skeletal muscle cells in SLCTs
      often reveal only moderate pleomorphism, and as they are closely admixed with the
      Sertoli cells or immature gonadal stroma, they can be rather difficult to
      differentiate from the latter ones. Immunohistochemical analysis with a panel of
      antibodies including antibodies against myogenin and alpha-inhibin is very
      important to diagnose the rhabdomyosarcoma and to grade the SLCT accurately.

PMID- 16979523
TI  - Myxoid lipoadenoma of parathyroid gland: a case report and literature review.
AB  - Myxoid lipoadenoma of the parathyroid gland is a rare variant of parathyroid
      adenoma. We present the case of a 40-year-old man with asymptomatic hypercalcemia
      who underwent surgical removal of a parathyroid adenoma. Histologically, the
      tumor consisted of monomorphous round-to-oval chief cells arranged in several
      architectural patterns including solid sheet-like, trabecular, and follicular.
      The tumor stroma was prominently myxoid with interspersed mature adipose tissue.
      Immunohistochemistry confirmed expression of thyroid transcription factor and
      parathyroid hormone by all tumor cells and a low proliferation rate with a Ki-67
      labeling index of at most 5%. Although the lesion exhibited characteristics that
      have been previously associated with "atypical parathyroid adenoma," such as
      dense fibrous bands within the tumor and a trabecular growth pattern, there was
      no further evidence, neither histologically nor clinically, for malignant
      behavior of the tumor.

PMID- 16979524
TI  - Basaloid squamous carcinoma of the larynx. A potential diagnostic pitfall.
AB  - Basaloid squamous carcinoma is a rare variant of squamous cell carcinoma. It is
      frequently diagnosed at an advanced stage with metastases. Histologically, it is
      identical to basaloid carcinoma at other anatomical sites. Some authors suggest
      that it may be associated with second primary tumors. Others implicate the
      Epstein-Barr and human papilloma viruses. All reports but one warn of its
      aggressive biological behavior. Our case concerns a 52-year-old man who had a
      small lesion in his right cord. Biopsy of the lesion was performed twice, and
      conventional squamous cell carcinoma was diagnosed; the patient returned 2 months
      later with progressed metastatic disease. The patient underwent a laryngectomy
      and a complete clinical and immunohistochemical investigation. Basaloid squamous
      carcinoma is a totipotential neoplasm with a grave prognosis. It can be
      misdiagnosed; therefore, the authors would like to emphasize the significance of
      this condition in comparison to conventional squamous cell carcinoma, and we
      provide a review of the relevant recent literature.

PMID- 16979525
TI  - Postradiation angiosarcoma of the small intestine: a case report and review of
      literature.
AB  - Postradiation angiosarcoma is typically a high-grade sarcoma that presents mainly
      in the skin and superficial tissues. Postradiation angiosarcoma arising in the
      small intestine is rare with only 11 cases documented in the English-language
      literature. Herein, we report a postradiation angiosarcoma of the small intestine
      9 years after radiotherapy for uterine cervical adenocarcinoma. The patient
      presented with symptoms of intestinal obstruction. At exploratory laparotomy,
      tumor nodules involved the small bowel. Microscopically, the neoplasm was
      composed of spindled and epithelioid cells arranged in solid aggregates and
      focally forming vascular channels. The diagnosis of angiosarcoma was confirmed
      immunohistochemically by tumor cell expression of CD31, CD34, and factor VIII
      related antigen. The patient died 10 months after laparotomy. The diagnosis of
      PRA should be entertained for any poorly differentiated neoplasm arising in a
      previously irradiated site. The correct diagnosis of PRA depends upon
      histomorphologic identification of vascular differentiation, coupled with
      immunohistochemical expression of endothelial-related markers.

PMID- 16979526
TI  - Epidermal growth factor receptor abnormalities in lung cancer. Pathogenetic and
      clinical implications.
AB  - The discovery that mutation of the tyrosine kinase domain of the epidermal growth
      factor receptor (EGFR) gene occurs in a subset of lung cancers and predicts for
      sensitivity to tyrosine kinase inhibitors has generated enormous interest and
      immediately led to intense basic, translational, and clinical research in many
      laboratories around the globe. All these findings have led to the identification
      of a subset of lung cancers with relatively distinct molecular, pathologic, and
      clinical features that demonstrate response to targeted therapy. Currently, the
      best marker to predict response and better survival for EGFR tyrosine kinase
      inhibitors, such as EGFR mutation, gene increased copy number, and protein
      immunohistochemical expression, is still controversial. Importantly, the findings
      of EGFR abnormalities in lung cancer have supported the notion that different
      molecular mechanisms and pathways are involved in the pathogenesis of lung cancer
      arising in never and ever smokers.

PMID- 16979528
TI  - A child with a systemic febrile illness - differential diagnosis and management.
AB  - Fever is a common symptom in children and may sometimes be prolonged or
      recurrent. There are many differential diagnoses, which may lead to significant
      diagnostic delay. Diagnosis is based on the clinical presentation as well as a
      widespread panel of investigations that are necessary in order to exclude the
      many potential causes of fever before reaching a definite diagnosis. In
      particular, the physician will look for infections and malignancies before
      considering the disease as inflammatory. This chapter reviews the differential
      diagnosis of prolonged or recurrent fever, and discusses most of the inflammatory
      syndromes presenting with fever.

PMID- 16979529
TI  - Fever and musculoskeletal symptoms in an adult: differential diagnosis and
      management.
AB  - Fever in the context of a patient with musculoskeletal symptoms is a sign of
      systemic inflammation. Initial management should be targeted at the
      identification of the organ systems affected and the search for a precise
      diagnosis. The main challenge is to differentiate between an infectious aetiology
      from an immune-inflammatory cause. Patient history and physical examination are
      key elements in the diagnostic work-up in order to direct appropriate laboratory
      investigations, as well as radiological and biopsy procedures. Advances in
      microbiological techniques and molecular genetics have provided additional tools
      for the clinician. Unfortunately, there is no simple algorithm to direct the
      diagnostic work-up, which still largely depends on the recognition of patterns of
      clinical presentations and the corresponding laboratory abnormalities.

PMID- 16979530
TI  - Acute polyarthritis.
AB  - Arthritis is the most common cause of disability. Hence, prompt recognition and
      management of acute-onset polyarthritis are paramount to prevent progressive
      damage. When rheumatoid arthritis is considered as a prototypical example of
      polyarthritis, the stakes of early and accurate evaluation are evident. The
      challenge is in determining when undifferentiated polyarthritis ends and
      rheumatoid arthritis begins. This chapter reviews the evidence to help clinicians
      identify and manage patients who present with acute polyarticular inflammation.

PMID- 16979531
TI  - Gout: can we create an evidence-based systematic approach to diagnosis and
      management?
AB  - The management of gout can be subdivided into four phases. Asymptomatic
      hyperuricaemia represents the basic underlying metabolic abnormality that can
      lead to gout. Studies are evaluating whether interventions may be indicated in
      some cases. Diagnostic criteria for gout and acute flares are still not well
      defined unless urate crystals are found. Acute attacks of gout are treated with
      anti-inflammatory measures and the agent of choice is often determined by attack
      stage, severity and comorbidities that may contra-indicate one or more agents.
      After attacks subside, there are asymptomatic periods during which decisions must
      be made about when and how to start urate-lowering measures. If hyperuricaemia
      persists, there is generally persistence of urate crystals in the joint. Anti
      inflammatory prophylaxis is needed when urate-lowering therapy is started.
      Lifestyle measures should be addressed. If chronic tophaceous gout is diagnosed,
      urate lowering should be started without delay. New agents are under development
      that may help with difficult cases.

PMID- 16979532
TI  - Systemic lupus erythematosus and pregnancy.
AB  - Women with systemic lupus erythematosus (SLE) face significant risks when
      embarking on a pregnancy, but attending a multidisciplinary clinic staffed by an
      experienced team can improve pregnancy outcome for women and their babies.
      Pregnancy in SLE should be planned and a management strategy should be agreed in
      full consultation with the patient, prior to conception. Pregnancy increases the
      likelihood of a lupus flare. It is not possible to predict when, or if, an
      individual patient will flare, although flare is more likely if disease has been
      active within 6 months of conception. Worsening of proteinuria in pregnancy could
      herald a lupus flare, but the differential diagnosis also includes the
      physiological response to pregnancy and pre-eclampsia. Corticosteroids,
      hydroxychloroquine and azathioprine are safe to use in pregnancy, with no adverse
      fetal effects reported despite many years of experience with their use. Correct
      identification of patients with antiphospholipid syndrome is important because
      treatment of affected women during pregnancy can improve fetal and maternal
      outcome. Neonatal SLE, although rare, carries a significant mortality and
      morbidity when the fetal heart is the targeted organ. Prophylaxis therapies,
      including treatment with intravenous immunoglobulin, await larger trials.

PMID- 16979534
TI  - Chronic low back pain in a working-age adult.
AB  - Low back pain is an extremely common patient complaint. Most cases resolve fairly
      quickly after the acute episode. However, a small but significant number of
      patients develop chronic low back pain; a persistent disabling condition.
      Patients suffer from unremitting pain and often become functionally impaired.
      Multiple patient characteristics have been identified that place patients at risk
      for developing chronic low back pain. Currently, it is difficult to find clinical
      guidelines on how best to manage chronic low back pain, and it remains a
      substantial treatment challenge for both physicians and patients. The causes,
      risk factors, prognosis and treatment strategies for chronic low back pain will
      be discussed in this chapter. The evidence regarding different pharmacological
      and non-pharmacological treatment modalities will be reviewed and a logical,
      focused treatment strategy will be outlined.

PMID- 16979533
TI  - Osteoporotic fractures in older adults.
AB  - Osteoporotic fractures are emerging as a major public health problem in the aging
      population. Fractures result in increased morbidity, mortality and health
      expenditures. This article reviews current evidence for the management of common
      issues following osteoporotic fractures in older adults including: (1)
      thromboembolism prevention; (2) delirium prevention; (3) pain management; (4)
      rehabilitation; (5) assessing the cause of fracture; and (6) prevention of
      subsequent fractures. Areas for practice improvement and further research are
      highlighted.

PMID- 16979535
TI  - Osteoarthritis: rational approach to treating the individual.
AB  - Osteoarthritis (OA) is the most common form of joint disease and the leading
      cause of pain and physical disability in older people. Risk factors for incidence
      and progression of osteoarthritis vary considerably according to the type of
      joint. Disease assessment is difficult and the relationship between the
      radiographic severity of joint damage and the incidence and severity of pain is
      only modest. Psychosocial and socio-economic factors play an important role. This
      chapter will discuss four main guiding principles to the management of OA: (1) to
      avoid overtreating people with mild symptoms; (2) to attempt to avoid doing more
      harm than good ('primum non nocere'); (3) to base patient management on the
      severity of pain, disability and distress, and not on the severity of joint
      damage or radiographic change; and (4) to start with advice about simple measures
      that patients can take to help themselves, and only progress to interventions
      that require supervision or specialist knowledge if simple measures fail. Effect
      sizes derived from meta-analyses of large randomized trials in OA are only small
      to moderate for most therapeutic interventions, but they are still valuable for
      patients and clinically relevant for physicians. Joint replacement may be the
      only option with a large effect size, but is only appropriate for the relatively
      small number of people with OA who have advanced disease and severe symptoms. The
      key to successful management involves patient and health professionals working
      together to develop optimal treatment strategies for the individual.

PMID- 16979536
TI  - Prevention of cardiovascular disease in patients with rheumatic diseases.
AB  - Cardiovascular disease (CVD), the leading cause of death in the USA, has emerged
      as an important comorbidity in the rheumatic diseases. As disease-modifying
      therapies have resulted in better disease control and decreases in disease
      associated mortality, it is now apparent that the prevalence of CVD and
      cardiovascular (CV) events is significantly increased in a number of rheumatic
      disorders when compared with age and gender-matched subjects from the general
      population. Investigations into the mechanisms of CVD in the general population
      have provided insights into potential mechanisms in rheumatic disease patients
      and possible aetiologies for their increased risk. Although there are no evidence
      based guidelines for CV risk factor screening and interventions specific to
      patients with rheumatic disease, the best current approach utilizes evidence
      based recommendations for the general population (and higher-risk subgroups)
      modified by what is known of CV risk factor and event prevalence in these
      patients.

PMID- 16979537
TI  - Problems encountered during anti-tumour necrosis factor therapy.
AB  - Worldwide, over 400,000 patients have been treated with tumour necrosis factor
      (TNF)-alpha antagonists for indications that include rheumatoid arthritis,
      juvenile rheumatoid arthritis, inflammatory bowel disease, psoriatic arthritis
      and ankylosing spondylitis. Since their approval, concerns regarding safety have
      been raised. There is a risk of re-activation of granulomatous diseases,
      especially tuberculosis, and measures should be taken for detection and treatment
      of latent tuberculosis infections. Preliminary data suggest that anti-TNF therapy
      may be safe in chronic hepatitis C. However, TNF-alpha antagonists have resulted
      in re-activation of chronic hepatitis B if not given concurrently with antiviral
      therapy. Solid tumours do not appear to be increased with anti-TNF therapy.
      Variable rates of increased lymphoma risk have been described with anti-TNF
      therapy compared with the general population, although no increased risk was
      found compared with a rheumatoid arthritis population. Large phase II and III
      trials with TNF-alpha antagonists in advanced heart failure have shown trends
      towards a worse prognosis, and should therefore be avoided in this population.
      Both etanercept and infliximab are associated with the formation of
      autoantibodies, and these autoantibodies are rarely associated with any specific
      clinical syndrome. Rare cases of aplastic anaemia, pancytopenia, vasculitis and
      demyelination have been described with anti-TNF therapy. This chapter will
      discuss the safety profile and adverse events of the three commercially available
      TNF-alpha antagonists: etanercept, infliximab and adalimumab. The data presented
      in this review have been collected from published data, individual case reports
      or series, package inserts, the Food and Drug Administration postmarketing
      adverse events surveillance system, and abstracts from the American College of
      Rheumatology and European Congress of Rheumatology meetings for 2005.

PMID- 16979538
TI  - Management of patients presenting with Sjogren's syndrome.
AB  - Sjogren's syndrome is an autoimmune exocrinopathy that predominantly affects
      salivary and lachrymal glands, leading to dry eyes and mouth. The most common
      clinical problems faced by the rheumatologist are those of dry eyes and mouth,
      parotid swelling, fatigue and extraglandular manifestations. The first stage in
      management is to make an accurate diagnosis based on the American/European
      consensus criteria. The most frequent differential diagnoses are dry eyes and
      mouth symptoms, a variant of chronic fatigue syndrome and fibromyalgia, and
      sialosis, which causes a non-inflammatory enlargement of the parotid glands. The
      mainstay of treatment for the sicca symptoms is local therapy, and that for the
      milder systemic symptoms is hydroxychloroquine. Steroids and immunosuppressive
      drugs are reserved for more severe extraglandular disease. In spite of intensive
      research in other systemic treatments including biologic therapies, there is
      limited evidence to support their use in routine clinical practice.

PMID- 16979539
TI  - Skin disorders with arthritis.
AB  - Many inflammatory, metabolic and infectious diseases affect the skin and joints.
      Most of these, such as rheumatoid arthritis and systemic lupus erythaematosus,
      are considered to be rheumatic conditions with secondary skin involvement.
      However, several primary cutaneous diseases are associated with arthritis and may
      even present with joint symptoms prior to cutaneous lesions. Common skin
      disorders, such as acne and psoriasis, have well-known musculoskeletal
      manifestations. Other less common conditions, such as dermatomyositis,
      multicentric reticulohistiocytosis, pyoderma gangrenosum, Sweet's syndrome and
      various cutaneous vasculitides, also have frequent joint involvement. This review
      will discuss the clinical presentation, both cutaneous and musculoskeletal,
      diagnosis and management of these disorders.

PMID- 16979540
TI  - Sea turtles.

PMID- 16979541
TI  - Social cognition.

PMID- 16979542
TI  - Does reduced heterozygosity depress sperm quality in wild rabbits (Oryctolagus
      cuniculus)?

PMID- 16979544
TI  - Variability in a taste-receptor gene determines whether we taste toxins in food.

PMID- 16979545
TI  - Circadian photoreception: spotlight on the brain.
AB  - In addition to its visual function, the mammalian eye detects light for a range
      of behavioral and physiological responses that are separate and apart from sight.
      Recent studies have begun to shed light on the areas of the brain that respond to
      such 'non-visual' photoreception in the human eye.

PMID- 16979546
TI  - Behavioural ecology: promiscuous fathers sire young that recognize true family.
AB  - Most theories of kin selection assume that animals are able to distinguish
      relatives from non-relatives. This is especially difficult in situations where
      mixed parentage precludes that relatedness is recognised by familiarity. Recent
      work shows that, within the same brood, young bluegill sunfish that are fathered
      by cuckolders--but not those sired by parental males--pick out their relatives
      using self-referent phenotype matching and not familiarity.

PMID- 16979547
TI  - Microtubule mechanics: a little flexibility goes a long way.
AB  - Microtubules are the least flexible of the cytoskeletal filaments, yet they are
      occasionally seen to be severely buckled in cells. A recent analysis suggests
      these buckles are evidence of high contractile forces throughout the cytoplasm,
      and that the other elements of the cytoskeleton laterally reinforce microtubules
      to help prevent their collapse.

PMID- 16979548
TI  - Naturalizing cognition: the integration of cognitive science and biology.
AB  - Descartes drove a wedge between human cognition and biology. Cognitive
      neuroscience is beginning to bridge the gap, and the application of mirror neuron
      theory to a range of problems in psychology has demonstrated the possibility of
      developing an understanding that spans from neural anatomy to language and
      empathy.

PMID- 16979549
TI  - Convergent evolution: gene sharing by eukaryotic plant pathogens.
AB  - Oomycetes and filamentous parasitic fungi are plant pathogens that have undergone
      convergent evolution. A recent study has shown that these microbial eukaryotes
      have exchanged metabolic genes, which might explain some of their phenotypic
      similarities.

PMID- 16979550
TI  - Frequency-dependent selection: when being different makes you not stand out.
AB  - A recent study reports frequency-dependent survival within highly variable guppy
      populations. Fitness advantages to rare genotypes may help maintain variation
      within populations, but the mechanisms underlying these advantages require
      further study.

PMID- 16979551
TI  - Centrosome duplication: is asymmetry the clue?
AB  - The structure of the yeast Sfi1-centrin complex, and its asymmetric position
      within the yeast centrosome, suggest a model for the initiation of centrosome
      duplication and provides a target for licensing this event.

PMID- 16979552
TI  - Inbreeding: when parents transmit more than genes.
AB  - Inbreeding in wild populations can have devastating effects on fitness, but the
      genetic causes should not be transmitted across generations. A new study of song
      sparrows has revealed a parent-offspring resemblance for inbreeding, resulting
      from population structuring, with important implications for understanding the
      genetic causes of phenotypic variation in wild populations.

PMID- 16979553
TI  - Calcium signaling: double duty for calcium at the mitochondrial uniporter.
AB  - Uptake of Ca(2+) by mitochondria serves as a regulator of a number of important
      cellular functions, including energy metabolism, cytoplasmic Ca(2+) signals, and
      apoptosis. Recent findings reveal that the process of Ca(2+) uptake by the
      mitochondrial uniporter is itself regulated by Ca(2+) in a temporally complex
      manner.

PMID- 16979554
TI  - Sex-peptide-regulated female sexual behavior requires a subset of ascending
      ventral nerve cord neurons.
AB  - BACKGROUND: Male-derived Sex-peptide (SP) elicits egg laying and rejection of
      courting males in mated Drosophila females. Little is known about the genes that
      specify the underlying neuronal circuits and mediate this switch in female sexual
      behavior. RESULTS: Here we show that the egghead gene involved in
      glycosphingolipid biosynthesis provides an essential component to the SP
      response. We have isolated viable alleles of the vital egghead gene that abolish
      egghead expression from a distal promoter resulting in the absence of the largest
      transcript of this complex transcription unit. Temporally and spatially
      restricted expression of egghead revealed a requirement for egghead early in the
      development of apterous-expressing ventral nerve cord neurons to rescue the SP
      response. In viable egghead alleles, these ascending interneurons, three per
      abdominal and seven per thoracic hemisegment, fail to innervate the central
      brain. egghead expression in apterous neurons rescues neuronal targeting and the
      response to SP. Furthermore, neurotransmission in apterous neurons is required to
      elicit the SP response. CONCLUSION: Together with the former finding of SP
      binding to afferent nerves , these results suggest that SP-mediated modification
      of sensory input switches female sexual behavior from the virgin to the mated
      state.

PMID- 16979555
TI  - The lipid-droplet proteome reveals that droplets are a protein-storage depot.
AB  - BACKGROUND: Lipid droplets are ubiquitous organelles that are among the basic
      building blocks of eukaryotic cells. Despite central roles for cholesterol
      homeostasis and lipid metabolism, their function and protein composition are
      poorly understood. RESULTS: We purified lipid droplets from Drosophila embryos
      and analyzed the associated proteins by capillary LC-MS-MS. Important functional
      groups include enzymes involved in lipid metabolism, signaling molecules, and
      proteins related to membrane trafficking. Unexpectedly, histones H2A, H2Av, and
      H2B were present. Using biochemistry, genetics, real-time imaging, and cell
      biology, we confirm that roughly 50% of certain embryonic histones are physically
      attached to lipid droplets, a localization conserved in other fly species.
      Histone association with droplets starts during oogenesis and is prominent in
      early embryos, but it is undetectable in later stages or in cultured cells.
      Histones on droplets are not irreversibly trapped; quantitation of droplet
      histone levels and transplantation experiments suggest that histones are
      transferred from droplets to nuclei as development proceeds. When this maternal
      store of histones is unavailable because lipid droplets are mislocalized, zygotic
      histone production starts prematurely. CONCLUSIONS: Because we uncover a striking
      proteomic similarity of Drosophila droplets to mammalian lipid droplets,
      Drosophila likely provides a good model for understanding droplet function in
      general. Our analysis also reveals a new function for these organelles; the
      massive nature of histone association with droplets and its developmental time
      course suggest that droplets sequester maternally provided proteins until they
      are needed. We propose that lipid droplets can serve as transient storage depots
      for proteins that lack appropriate binding partners in the cell. Such
      sequestration may provide a general cellular strategy for handling excess
      proteins.

PMID- 16979556
TI  - Reconstructing and deconstructing agonist-induced activation of integrin
      alphaIIbbeta3.
AB  - BACKGROUND: Integrin receptors, composed of transmembrane alpha and beta
      subunits, are essential for the development and functioning of multicellular
      animals. Agonist stimulation leads cells to regulate integrin affinity
      ("activation"), thus controlling cell adhesion and migration, controlling
      extracellular-matrix assembly, and contributing to angiogenesis, tumor cell
      metastasis, inflammation, the immune response, and hemostasis. A final step in
      integrin activation is the binding of talin, a cytoskeletal protein, to integrin
      beta cytoplasmic domains. Many different signaling molecules that regulate
      integrin affinity have been described, but a pathway that connects agonist
      stimulation to talin binding and activation has not been mapped. RESULTS: We used
      forward, reverse, and synthetic genetics to engineer and order an integrin
      activation pathway in cells expressing a prototype activatable integrin, platelet
      alphaIIbbeta3. Phorbol myristate acetate (PMA) activated alphaIIbbeta3 only after
      the increased expression of both recombinant protein kinase Calpha (PKCalpha) and
      talin to levels approximating those in platelets. Inhibition of Rap1 GTPase
      reduced alphaIIbbeta3 activation, whereas activated Rap1A(G12V) bypassed the
      requirement for PKC, establishing that Rap1 is downstream of PKC. Talin binding
      to integrins mediates Rap1-induced activation because Rap1A(G12V) failed to
      activate alphaIIbbeta3 in cells expressing integrin binding-defective talin
      (W359A). Rap1 activated integrins by forming an integrin-associated complex
      containing talin in combination with the Rap effector, RIAM. Furthermore, siRNA
      mediated knockdown of RIAM blocked integrin activation. CONCLUSIONS: We have, for
      the first time, ordered a pathway from agonist stimulation to integrin activation
      and established the Rap1-induced formation of an "integrin activation complex,"
      containing RIAM and talin, that binds to and activates the integrin.

PMID- 16979557
TI  - Promiscuity drives self-referent kin recognition.
AB  - Kin selection theory has been one of the most significant advances in our
      understanding of social behavior . However, the discovery of widespread
      promiscuity has challenged the evolutionary importance of kin selection because
      it reduces the benefit associated with helping nestmates . This challenge would
      be resolved if promiscuous species evolved a self-referent kin-recognition
      mechanism that enables individuals to differentiate kin and nonkin . Here, we
      take advantage of an asymmetry in the level of promiscuity among males of
      alternative life histories in the bluegill sunfish (Lepomis macrochirus). We show
      that, as a consequence of this asymmetry, offspring of "parental" males have a
      high level of relatedness to nestmates, whereas offspring of "cuckolder" males
      have a low level of relatedness to nestmates. We find that offspring of parentals
      do not use a direct recognition mechanism to discriminate among nestmates,
      whereas offspring of cuckolders use kin recognition by self-referent phenotype
      matching to differentiate between kin and nonkin. Furthermore, we estimate that
      the cost of utilizing such self-referent kin recognition is equivalent to a
      relatedness (R) of at least 0.06. These results provide compelling evidence for
      adaptive use of kin recognition by self-referent phenotype matching and confirm
      the importance of kinship in social behavior.

PMID- 16979558
TI  - A taste receptor required for the caffeine response in vivo.
AB  - Caffeine is a methylxanthine present in the coffee tree, tea plant, and other
      naturally occurring sources and is among the most commonly consumed drugs
      worldwide. Whereas the pharmacological action of caffeine has been studied
      extensively, relatively little is known concerning the molecular mechanism
      through which this substance is detected as a bitter compound. Unlike most
      tastants, which are detected through cell-surface G protein-coupled receptors, it
      has been proposed that caffeine and related methylxanthines activate taste
      receptor cells through inhibition of a cyclic nucleotide phosphodiesterase (PDE)
      . Here, we show that the gustatory receptor Gr66a is expressed in the dendrites
      of Drosophila gustatory receptor neurons and is essential for the caffeine
      response. In a behavioral assay, the aversion to caffeine was specifically
      disrupted in flies missing Gr66a. Caffeine-induced action potentials were also
      eliminated, as was the response to theophylline, the methylxanthine in tea. The
      Gr66a mutant exhibited normal tastant-induced action potentials upon presentation
      of theobromine, a methylxanthine in cocoa. Given that theobromine and caffeine
      inhibit PDEs with equal potencies , these data further support the role of Gr66a
      rather than a PDE in mediating the caffeine response. Gr66a is the first
      gustatory receptor shown to be essential for caffeine-induced behavior and
      activity of gustatory receptor cells in vivo.

PMID- 16979559
TI  - Congruent embodied representations for visually presented actions and linguistic
      phrases describing actions.
AB  - The thesis of embodied semantics holds that conceptual representations accessed
      during linguistic processing are, in part, equivalent to the sensory-motor
      representations required for the enactment of the concepts described . Here,
      using fMRI, we tested the hypothesis that areas in human premotor cortex that
      respond both to the execution and observation of actions-mirror neuron areas -are
      key neural structures in these processes. Participants observed actions and read
      phrases relating to foot, hand, or mouth actions. In the premotor cortex of the
      left hemisphere, a clear congruence was found between effector-specific
      activations of visually presented actions and of actions described by literal
      phrases. These results suggest a key role of mirror neuron areas in the re
      enactment of sensory-motor representations during conceptual processing of
      actions invoked by linguistic stimuli.

PMID- 16979560
TI  - Empathy and the somatotopic auditory mirror system in humans.
AB  - How do we understand the actions of other individuals if we can only hear them?
      Auditory mirror neurons respond both while monkeys perform hand or mouth actions
      and while they listen to sounds of similar actions . This system might be
      critical for auditory action understanding and language evolution . Preliminary
      evidence suggests that a similar system may exist in humans . Using fMRI, we
      searched for brain areas that respond both during motor execution and when
      individuals listened to the sound of an action made by the same effector. We show
      that a left hemispheric temporo-parieto-premotor circuit is activated in both
      cases, providing evidence for a human auditory mirror system. In the left
      premotor cortex, a somatotopic pattern of activation was also observed: A dorsal
      cluster was more involved during listening and execution of hand actions, and a
      ventral cluster was more involved during listening and execution of mouth
      actions. Most of this system appears to be multimodal because it also responds to
      the sight of similar actions. Finally, individuals who scored higher on an
      empathy scale activated this system more strongly, adding evidence for a possible
      link between the motor mirror system and empathy.

PMID- 16979561
TI  - Self and other in the human motor system.
AB  - Observation of another's action can selectively facilitate the brain's motor
      circuits for making the same action . A "mirror-matching mechanism" might map
      observed actions onto the observer's own motor representations . Crucially, this
      view suggests that the brain represents others' actions like one's own. However,
      this hypothesis has been difficult to test because the experience of one's own
      body differs from that of others' bodies with respect to viewpoint, morphological
      features, familiarity, and the hallmark feature of kinaesthetic experience. We
      used an established method for manipulating the sense of body ownership ("rubber
      hand illusion") to compare effects of observing actions that either were or were
      not illusorily attributed to the subject's own body. We show that observing
      another's actions facilitated the motor system, whereas observing identical
      actions, which were illusorily attributed to the subject's own body, showed the
      opposite pattern. Thus, motor facilitation strongly depends on the agent to whom
      the observed action is attributed. This result contradicts previous concepts of
      equivalence between one's own actions and actions of others and suggests that
      social differentiation, not equivalence, is characteristic of the human action
      system.

PMID- 16979563
TI  - Sequential protein recruitment in C. elegans centriole formation.
AB  - Formation of the microtubule-based centriole is a poorly understood process that
      is crucial for duplication of the centrosome, the principal microtubule
      organizing center of animal cells . Five proteins have been identified as being
      essential for centriole formation in Caenorhabditis elegans: the kinase ZYG-1, as
      well as the coiled-coil proteins SAS-4, SAS-5, SAS-6, and SPD-2 . The
      relationship between these proteins is incompletely understood, limiting
      understanding of how they contribute to centriole formation. In this study, we
      established the order in which these five proteins are recruited to centrioles,
      and we conducted molecular epistasis experiments expanding on earlier work. We
      find that SPD-2 is loaded first and is needed for the centriolar localization of
      the four other proteins. ZYG-1 recruitment is required thereafter for the
      remaining three proteins to localize to centrioles. SAS-5 and SAS-6 are recruited
      next and are needed for the presence of SAS-4, which is incorporated last. Our
      results indicate in addition that the presence of SAS-5 and SAS-6 allows
      diminution of centriolar ZYG-1. Moreover, astral microtubules appear dispensable
      for the centriolar recruitment of all five proteins. Several of these proteins
      have homologs in other metazoans, and we expect the assembly pathway that stems
      from our work to be conserved.

PMID- 16979562
TI  - Activity-independent prespecification of synaptic partners in the visual map of
      Drosophila.
AB  - Specifying synaptic partners and regulating synaptic numbers are at least partly
      activity-dependent processes during visual map formation in all systems
      investigated to date . In Drosophila, six photoreceptors that view the same point
      in visual space have to be sorted into synaptic modules called cartridges in
      order to form a visuotopically correct map . Synapse numbers per photoreceptor
      terminal and cartridge are both precisely regulated . However, it is unknown
      whether an activity-dependent mechanism or a genetically encoded developmental
      program regulates synapse numbers. We performed a large-scale quantitative
      ultrastructural analysis of photoreceptor synapses in mutants affecting the
      generation of electrical potentials (norpA, trp;trpl), neurotransmitter release
      (hdc, syt), vesicle endocytosis (synj), the trafficking of specific guidance
      molecules during photoreceptor targeting (sec15), a specific guidance receptor
      required for visual map formation (Dlar), and 57 other novel synaptic mutants
      affecting 43 genes. Remarkably, in all these mutants, individual photoreceptors
      form the correct number of synapses per presynaptic terminal independently of
      cartridge composition. Hence, our data show that each photoreceptor forms a
      precise and constant number of afferent synapses independently of neuronal
      activity and partner accuracy. Our data suggest cell-autonomous control of
      synapse numbers as part of a developmental program of activity-independent steps
      that lead to a "hard-wired" visual map in the fly brain.

PMID- 16979564
TI  - A role for PtdIns(4,5)P2 and PIP5Kalpha in regulating stress-induced apoptosis.
AB  - The phosphoinositide phosphatidylinositol 4, 5-bisphosphate (PtdIns(4,5)P(2)) is
      essential for many cellular processes and is linked to the etiology of numerous
      human diseases . PtdIns(4,5)P(2) has been indirectly implicated as a negative
      regulator of apoptosis ; however, it is unclear if apoptotic stimuli negatively
      regulate PtdIns(4,5)P(2) levels in vivo. Here, we show that two apoptotic-stress
      stimuli, hydrogen peroxide (H(2)O(2)) and UV irradiation, cause PtdIns(4,5)P(2)
      depletion during programmed cell death independently of and prior to caspase
      activation. Depletion of PtdIns(4,5)P(2) is essential for apoptosis because
      maintenance of PtdIns(4,5)P(2) levels by overexpression of PIP5Kalpha rescues
      cells from H(2)O(2)-induced apoptosis. PIP5Kalpha expression promotes both basal
      and sustained ERK1/2 activation after H(2)O(2) treatment, and importantly,
      pharmacological inhibition of ERK1/2 signaling blocks PIP5Kalpha-mediated cell
      survival. H(2)O(2) induces tyrosine phosphorylation and translocation of
      PIP5Kalpha away from its substrate at the plasma membrane, and both are dependent
      upon the activity of c-src family kinases. Furthermore, constitutively active c
      src enhances tyrosine phosphorylation of PIP5Kalpha in vivo and is sufficient for
      the translocation of PIP5Kalpha away from the plasma membrane. These observations
      demonstrate that certain apoptotic stimuli initiate an essential signaling
      pathway during cell death, and this pathway leads to caspase-independent
      downregulation of PIP5Kalpha and its product PtdIns(4,5)P(2).

PMID- 16979565
TI  - Evolution of filamentous plant pathogens: gene exchange across eukaryotic
      kingdoms.
AB  - Filamentous fungi and oomycetes are eukaryotic microorganisms that grow by
      producing networks of thread-like hyphae, which secrete enzymes to break down
      complex nutrients, such as wood and plant material, and recover the resulting
      simple sugars and amino acids by osmotrophy. These organisms are extremely
      similar in both appearance and lifestyle and include some of the most
      economically important plant pathogens . However, the morphological similarity of
      fungi and oomycetes is misleading because they represent some of the most
      distantly related eukaryote evolutionary groupings, and their shared osmotrophic
      growth habit is interpreted as being the result of convergent evolution . The
      fungi branch with the animals, whereas the oomycetes branch with photosynthetic
      algae as part of the Chromalveolata . In this report, we provide strong
      phylogenetic evidence that multiple horizontal gene transfers (HGT) have occurred
      from filamentous ascomycete fungi to the distantly related oomycetes. We also
      present evidence that a subset of the associated gene families was initially the
      product of prokaryote-to-fungi HGT. The predicted functions of the gene products
      associated with fungi-to-oomycete HGT suggest that this process has played a
      significant role in the evolution of the osmotrophic, filamentous lifestyle on
      two separate branches of the eukaryote tree.

PMID- 16979566
TI  - Fifty years of interferon research: aiming at a moving target.
AB  - Nearly half a century has passed since the first published description of
      interferons (IFNs). This commentary introduces the four accompanying review
      articles on type I IFN research and attempts to relate how the field of IFN
      research has been changing during its history.

PMID- 16979567
TI  - Type I interferon [corrected] gene induction by the interferon regulatory factor
      family of transcription factors.
AB  - Induction of type I interferons (IFNs) by viruses and other pathogens is crucial
      for innate immunity, and it is mediated by the activation of pattern-recognition
      receptors, such as Toll-like receptors and cytosolic receptors such as RIG-I and
      MDA5. The type I IFN induction is primarily controlled at the gene
      transcriptional level, wherein a family of transcription factors, interferon
      regulatory factors (IRFs), plays central roles. Here, we summarize the recent
      studies on IRFs, providing a paradigm of how genes are ingeniously regulated
      during immune responses. We also consider some evolutional aspects on the IFN-IRF
      system.

PMID- 16979568
TI  - Complex modulation of cell type-specific signaling in response to type I
      interferons.
AB  - The type I interferons (IFNs) are pleiotropic cytokines that regulate many
      different cellular functions. The major signaling pathway activated by type I
      IFNs involves sequential phosphorylation of the tyrosine residues of the Janus
      kinase (JAK) and signal transducers and activators of transcription (STAT)
      proteins, providing the primary mechanism through which gene expression is
      induced. Recent work has shown that the responses are quite complex, as shown by
      different responses to specific subtypes of type I IFN, activation of kinases in
      addition to JAKs, patterns of activation of all seven STATs in different cells,
      and activation of transcription factors other than STATs. The type I IFNs use
      this complexity to regulate many different biological functions in different
      types of cells, by activating different specific signals and patterns of gene
      expression.

PMID- 16979569
TI  - Type I interferons in host defense.
AB  - Type I interferons (IFNs) are a family of cytokines specialized to coordinate
      immunity to viruses and other intracellular infections. In the past several
      years, many of the receptors and signaling pathways that link pathogen detection
      to induction of type I IFNs have been identified and characterized. An integrated
      picture has emerged in which type I IFNs have essential functions in several
      seemingly disparate processes: they restrict viral spread by engaging machinery
      that ultimately cripples and kills infected cells, yet they are also positively
      linked to the activation and expansion of lymphocytes that are important for
      control of intracellular infections. These advances highlight the context
      specific actions of type I IFNs and clarify the multiple points at which they are
      integrated into both innate and adaptive immunity.

PMID- 16979570
TI  - Type I interferon in systemic lupus erythematosus and other autoimmune diseases.
AB  - Different genetic alterations may lead to type I interferon (IFN) overproduction
      in human systemic lupus erythematosus (SLE). The increased bioavailability of
      type I IFN contributes to peripheral tolerance breakdown through the activation
      of immature myeloid dendritic cells (mDCs). IFN-matured mDCs activate
      autoreactive T cells. These cells, together with plasmacytoid DCs, help expand
      autoreactive B cells. IFN-matured DCs also activate cytotoxic CD8+ T cells,
      possibly increasing apoptotic cell availability. The capture of apoptotic cells
      by mDCs and of nucleic acid-containing immune complexes by plasmacytoid DCs and B
      cells amplifies the autoimmune reaction leading to disease manifestations.
      Genetic alterations in lineages other than B cells might explain other autoimmune
      syndromes where type I IFNs appear to be involved.

PMID- 16979571
TI  - A failure to launch: fuelling cytokine secretion in iNKT cells.
AB  - In this issue of Immunity, Bezbradica et al., (2006) uncover an unsuspected role
      for the cytokine GM-CSF in the thymic development of invariant NKT cells, a role
      that licenses these cells to secrete effector cytokines upon activation in the
      periphery.

PMID- 16979572
TI  - Unraveling the warp and weft of B cell fate.
AB  - Two recent Immunity articles (Enzler et al., 2006; Sasaki et al., 2006) probe the
      roles of Nuclear Factor kappa-B (NF-kappaB) pathways in survival and
      differentiation mediated by B cell activation factor of the TNF family (BAFF).

PMID- 16979573
TI  - Tolling for autoimmunity-prime time for 7.
AB  - The reason certain self-antigens are consistently targeted by autoantibodies may
      be because they are self-adjuvants. Two papers in this issue of Immunity provide
      important insights into the contribution of Toll-like receptors in systemic
      autoimmune disease (Berland et al., 2006; Christensen et al., 2006).

PMID- 16979574
TI  - Transforming growth factor-beta: taking control of T cells' life and death.
AB  - To determine how transforming growth factor-beta (TGF-beta) controls T cell
      function, Marie et al. (2006) and Li et al. (2006a) created mice with T cells
      lacking TGF-beta signaling receptors. Both report that TGF-beta signaling by T
      cells is absolutely essential for tolerance and homeostasis.

PMID- 16979575
TI  - Formation of fluorescent proteins by the attachment of phycoerythrobilin to R
      phycoerythrin alpha and beta apo-subunits.
AB  - Formation of fluorescent proteins was explored after incubation of recombinant
      apo-subunits of phycobiliprotein R-phycoerythrin with phycoerythrobilin
      chromophore. Alpha and beta apo-subunit genes of R-phycoerythrin from red algae
      Polisiphonia boldii were cloned in plasmid pET-21d(+). Hexahistidine-tagged alpha
      and beta apo-subunits were expressed in Escherichia coli. Although expressed apo
      subunits formed inclusion bodies, fluorescent holo-subunits were constituted
      after incubation of E. coli cells with phycoerythrobilin. Holo-subunits contained
      both phycoerythrobilin and urobilin chromophores. Fluorescence and differential
      interference contrast microscopy showed polar location of holo-subunit inclusion
      bodies in bacterial cells. Cells containing fluorescent holo-subunits were
      several times brighter than control cells as found by fluorescence microscopy and
      flow cytometry. The addition of phycoerythrobilin to cells did not show cytotoxic
      effects, in contrast to expression of proteins in inclusion bodies. In an attempt
      to improve solubility, R-phycoerythrin apo-subunits were fused to maltose-binding
      protein and incubated with phycoerythrobilin both in vitro and in vivo. Highly
      fluorescent soluble fusion proteins containing phycoerythrobilin as the sole
      chromophore were formed. Fusion proteins were localized by fluorescence
      microscopy either throughout E. coli cells or at cell poles. Flow cytometry
      showed that cells containing fluorescent fusion proteins were up to 10 times
      brighter than control cells. Results indicate that fluorescent proteins formed by
      attachment of phycoerythrobilin to expressed apo-subunits of phycobiliproteins
      can be used as fluorescent probes for analysis of cells by microscopy and flow
      cytometry. A unique property of these fluorescent reporters is their utility in
      both properly folded (soluble) subunits and subunits aggregated in inclusion
      bodies.

PMID- 16979576
TI  - Monitoring activation sites on polysaccharides by GC-MS.
AB  - A method has been developed to determine the location and order of activation for
      potential saccharide antigens used in conjugate vaccine development. Saccharides
      were monitored for activation by sodium periodate oxidation and subsequent
      analysis by gas chromatography-mass spectrometry (GC-MS). Pneumococcal serotype
      polysaccharides 7F and 18C were evaluated as polysaccharides containing multiple
      potential sites for activation. Sialyllactose was used as a model oligosaccharide
      compound to evaluate oxidation of terminally linked sialic acids and reducing
      sugar residues. Oxidized saccharides were analyzed by monosaccharide composition
      and/or linkage analysis to elucidate specific activation of cis versus trans
      diols, as well as diols containing primary versus secondary alcohols, at
      specified levels of periodate. Samples (100-500 microg) were sequentially
      oxidized, reduced, methanolyzed, and derivatized in a single reaction vial for
      routine analysis by GC-MS.

PMID- 16979577
TI  - Spectrophotometric assay for calcineurin activity in leukocytes isolated from
      human blood.
AB  - The calcineurin inhibitors, cyclosporine and tacrolimus, still constitute the
      cornerstone of immunosuppressive regimen after organ transplantation. An
      efficient and feasible way to measure calcineurin activity and inhibition by
      these drugs may improve therapeutic monitoring of these drugs in transplant
      recipients. Calcineurin activity was measured in leukocyte lysates isolated from
      human blood using spectrophotometric phosphate quantification. The
      dephosphorylation of a 19-amino acid peptide substrate of calcineurin was
      determined using the Malachite green phosphate reagent in the presence of okadaic
      acid and with and without the calcium chelator EGTA. Sample storage and lysis
      buffer components were among the variables optimized, and the inhibitory effect
      of calcineurin inhibitors was investigated. Observed loss of calcineurin activity
      during sample storage was eliminated by adding ascorbic acid to lysis buffer. The
      final inter- and intraassay variation coefficients were 10 and 4.5%,
      respectively, and the detection limit was 15 pmol min(-1)x10(6) WBC(-1), where
      WBC is white blood cells (leukocytes). In vitro IC50 values were 212 and 34
      microg/L for cyclosporine and tacrolimus, respectively. In vivo calcineurin
      inhibition was observed when calcineurin activity was measured in transplant
      recipients on maintenance therapy with cyclosporine and tacrolimus.

PMID- 16979578
TI  - Urea as the only inactivator of RNase for extraction of total RNA from plant and
      animal tissues.

PMID- 16979579
TI  - "Tissue" transglutaminase contributes to the formation of disulphide bridges in
      proteins of mitochondrial respiratory complexes.
AB  - In this study we provide the first in vivo evidences showing that, under
      physiological conditions, "tissue" transglutaminase (TG2) might acts as a protein
      disulphide isomerase (PDI) and through this activity contributes to the correct
      assembly of the respiratory chain complexes. Mice lacking TG2 exhibit
      mitochondrial energy production impairment, evidenced by decreased ATP levels
      after physical challenge. This defect is phenotypically reflected in a dramatic
      decrease of motor behaviour of the animals. We propose that the molecular
      mechanism, underlying such a phenotype, resides in a defective disulphide bonds
      formation in ATP synthase (complex V), NADH-ubiquinone oxidoreductase (complex
      I), succinate-ubiquinone oxidoreductase (complex II) and cytochrome c oxidase
      (complex IV). In addition, TG2-PDI might control the respiratory chain by
      modulating the formation of the prohibitin complexes. These data elucidate a new
      pathway that directly links the TG2-PDI enzymatic activity with the regulation of
      mitochondrial respiratory chain function.

PMID- 16979580
TI  - Myristoylation of human LanC-like protein 2 (LANCL2) is essential for the
      interaction with the plasma membrane and the increase in cellular sensitivity to
      adriamycin.
AB  - Human LANCL2, also known as Testis-specific Adriamycin Sensitivity Protein
      (TASP), is a member of the highly conserved and widely distributed lanthionine
      synthetase component C-like (LANCL) protein family. Expression studies of tagged
      LANCL2 revealed the major localization to the plasma membrane, juxta-nuclear
      vesicles, and the nucleus, in contrast to the homologue LANCL1 that was mainly
      found in the cytosol and nucleus. We identified the unique N-terminus of LANCL2
      to function as the membrane anchor and characterized the relevant N-terminal
      myristoylation and a basic phosphatidylinositol phosphate-binding site.
      Interestingly, the non-myristoylated protein was confined to the nucleus
      indicating that the myristoylation targets LANCL2 to the plasma membrane.
      Cholesterol depletion by methyl-beta-cyclodextrin caused the partial dissociation
      of overexpressed LANCL2 from the plasma membrane in vitro, whereas in vivo we
      observed an enhanced cell detachment from the matrix. We found that overexpressed
      LANCL2 interacts with the cortical actin cytoskeleton and therefore may play a
      role in cytoskeleton reorganization and in consequence to cell detachment.
      Moreover, we confirmed previous data that LANCL2 overexpression enhances the
      cellular sensitivity to the anticancer drug adriamycin and found that this
      sensitivity is dependent on the myristoylation and membrane association of
      LANCL2.

PMID- 16979581
TI  - A controlled evaluation of group cognitive therapy in the treatment of irritable
      bowel syndrome.
AB  - We randomized, at two sites, 210 patients with Rome II diagnosed irritable bowel
      syndrome (IBS), of at least moderate severity, to one of three conditions: group
      based cognitive therapy (CT; n=120), psychoeducational support groups (n=46) as
      an active control, or intensive symptom and daily stress monitoring (n=44). One
      hundred eighty-eight participants completed the initial treatment. Those in
      symptom monitoring were then crossed over to CT. For an intent to treat analysis
      on a composite GI symptom measure derived from daily symptom diaries, both CT and
      the psychoeducational support groups were significantly more improved than those
      in the intensive symptom monitoring condition, but the CT and psychoeducational
      support group did not differ. Among treatment completers on the same composite
      measure of GI symptoms, again, both CT and psychoeducational support groups were
      statistically superior to symptom monitoring but did not differ on the symptom
      composite, or on any other measure. On individual IBS symptoms, both CT and
      psychoeducational support were statistically superior to symptom monitoring on
      reductions in abdominal pain and tenderness and for flatulence. Patient global
      ratings at the end of treatment showed the two active conditions statistically
      superior to symptom monitoring on change in Bowel Regularity, with CT superior to
      symptom monitoring on reduction in overall pain and in improvement in sense of
      well-being. Three-month follow-up data on 175 patients revealed maintenance of
      significant improvement or continued significant improvement on all IBS symptoms,
      including the McGill Pain Questionnaire. Group CT and psychoeducational support
      groups continued not to differ on any measure. We thus conclude that group CT is
      not superior to an attention placebo control condition.

PMID- 16979582
TI  - Tryptophan and tyrosine to terbium fluorescence resonance energy transfer as a
      method to "map" aromatic residues and monitor docking.
AB  - Fluorescent lanthanide ions, with large Stokes shifts and narrow emission bands,
      are excellent tools for the development of FRET-based assays. In this work, a
      terbium ion is tethered to a peptide which binds to the BIR3 domain of XIAP, an
      anti-apoptotic protein. Excitation of tryptophan and tyrosine residues in the
      BIR3 domain causes the peptide bound terbium ion to fluoresce relative to its
      distance from these aromatic residues. By developing ligands with terbium ions
      tethered at different residues, the relative terbium emission can be used to
      "map" the aromatic residues within the ligand binding pocket.

PMID- 16979583
TI  - Biophysical characterization of an indolinone inhibitor in the ATP-binding site
      of DNA gyrase.
AB  - Fighting bacterial resistance is a challenging task in the field of medicinal
      chemistry. DNA gyrase represents a validated antibacterial target and has drawn
      much interest in recent years. By a structure-based approach we have previously
      discovered compound 1, an indolinone derivative, possessing inhibitory activity
      against DNA gyrase. In the present paper, a detailed biophysical characterization
      of this inhibitor is described. Using mass spectrometry, NMR spectroscopy, and
      fluorescence experiments we have demonstrated that compound 1 binds reversibly to
      the ATP-binding site of the 24 kDa N-terminal fragment of DNA gyrase B from
      Escherichia coli (GyrB24) with low micromolar affinity. Based on these data, a
      plausible molecular model of compound 1 in the active site of GyrB24 was
      constructed. The predicted binding mode explains the competitive inhibitory
      mechanism with respect to ATP and forms a useful basis for further development of
      potent DNA gyrase inhibitors.

PMID- 16979584
TI  - ER stress contributes to ischemia-induced cardiomyocyte apoptosis.
AB  - Myocardial ischemia is a severe stress condition that leads to loss of
      cardiomyocytes. The cell loss is attributed to apoptosis, although the exact
      mechanisms involved are only partially defined, which limits therapeutic
      opportunities. Here, we show caspase activation and apoptosis in neonatal rat
      cardiomyocyte cultures subjected to simulated ischemia by serum, glucose, and
      oxygen deprivation (SGO). Caspase activation was preceded by endoplasmic
      reticulum (ER) stress and the activation of the unfolded protein response (UPR),
      detected by the induction of Grp78, induction and splicing of XBP1, and
      phosphorylation of eukaryotic initiation factor 2-alpha (eIF2alpha). At a later
      time the ER stress response switched from UPR and cytoprotective response to a
      pro-apoptotic response as demonstrated by the upregulation of CHOP and processing
      of pro-caspase-12. Thus, we provide evidence that the ER can generate and
      propagate apoptotic signals in response to ischemic stress and this pathway is
      therefore a novel target for prevention of ischemia-mediated cardiomyocyte loss.

PMID- 16979585
TI  - Inhibition of the catalytic activity of trans-acting antigenomic delta ribozyme
      by selected antibiotics and their Cu2+ complexes.
AB  - The effect of selected 10 antibiotics and their complexes with Cu(2+) ions on the
      catalytic activity of the trans-acting antigenomic delta ribozyme was
      investigated. Sisomicin, vancomycin, and actinomycin D displayed weak inhibitory
      properties. However, much stronger effects were detected with complexes of these
      antibiotics with Cu(2+) ions. The strongest inhibition was observed with
      actinomycin D-Cu(2+) complex, for which the calculated K(i) value was reduced ca.
      35-fold upon metal ion complexation. We postulate that the antibiotic-Cu(2+)
      complexes are guided to the ribozyme metal ion binding site(s) presumably
      displacing the catalytically important metal ion(s). Moreover, we assume that,
      once positioned in appropriate distances to RNA phosphate groups and bases, the
      coordinated Cu(2+) ions become positively charged factors that enhance the
      affinity of the antibiotics to the ribozyme. These observations indicate that
      coordination of metal ions to antibiotics substantially changes their properties
      which might also have a biological relevance inside the cell.

PMID- 16979586
TI  - Inositol hexaphosphate represses telomerase activity and translocates TERT from
      the nucleus in mouse and human prostate cancer cells via the deactivation of Akt
      and PKCalpha.
AB  - Inositol hexaphosphate (IP6) has anti-proliferative effects on a variety of
      cancer cells, including prostate cancer. However, the molecular mechanism of anti
      proliferative effects of IP6 is not entirely understood. Since the activation of
      telomerase is crucial for cells to gain immortality and proliferation ability, we
      examined the role of IP6 in the regulation of telomerase activity in prostate
      cancer cells. Here, we show that IP6 represses telomerase activity in mouse and
      human prostate cancer cells dose-dependently. In addition, IP6 prevents the
      translocation of TERT to the nucleus. Since phosphorylation of TERT by Akt and/or
      PKCalpha is necessary for nuclear translocation, we examined phosphorylation of
      Akt and PKCalpha after IP6 treatments. Our results show that IP6 inhibits
      phosphorylation of Akt and PKCalpha. These results show for the first time that
      IP6 represses telomerase activity in prostate cancer cells by posttranslational
      modification of TERT via the deactivation of Akt and PKCalpha.

PMID- 16979587
TI  - Abeta 11-40/42 production without gamma-secretase epsilon-site cleavage.
AB  - The accumulation and deposition of fibrillar Abeta is thought to be the primary
      cause of Alzheimer's disease. Abeta is derived from Alzheimer amyloid precursor
      protein (APP) by sequential proteolytic cleavage involving beta- and gamma
      secretase. Recently, gamma-secretase was shown to cleave near the cytoplasmic
      membrane boundary of APP (called the epsilon-cleavage), as well as in the middle
      of the membrane domain (gamma-cleavage). It has been reported that the C-terminus
      of Abeta is generated via a series of sequential cleavages, epsilon-cleavage
      followed by gamma-cleavage. However, recent article has reported that gamma- and
      epsilon-site cleavage are regulated independently. The relationship between gamma
      site and epsilon-site cleavage is still unknown. In this study, we analyzed the
      generation of AICD and Abeta in CHO cells expressing APP derivatives. We found
      that epsilon-site cleavage preferentially occurs alpha-secretase processing
      product, and that Abeta 11-40/42 was generated without gamma-secretase epsilon
      site cleavage, indicating that gamma-site cleavage and epsilon-site cleavage were
      regulated differentially.

PMID- 16979588
TI  - HPV16E7 mediates HADC chromatin repression and downregulation of MHC class I
      genes in HPV16 tumorigenic cells through interaction with an MHC class I
      promoter.
AB  - Downregulation of the expression of major histocompatibility complex class I
      antigens on the surface of high-risk HPVs-transformed cells may contribute to
      their high tumorigenic potential, which enables them to escape immune recognition
      by cytotoxic T lymphocytes. In this study, we show that the viral E7 oncoprotein
      mediates transcriptional downregulation of the major histocompatibility complex
      (MHC) class I genes by targeting the class I promoter in HPV16 containing CaSki
      tumor cells. Using the chromatin immunoprecipitation assay, we demonstrated that
      HPV16E7 and specific HADCs, including HADC1, HADC2, and HADC8, are physically
      associated with the class I promoter and the histone of the class I promoter was
      deacetylated. Knocking down of HPV16E7 expression with the E7-specific small
      interfering RNA induced the release of HPV17E7 as well as HDAC1 and HDAC2 from
      the class I promoter. Furthermore, HPV16E7 siRNA resulted in a dramatic increase
      in histone acetylation. Importantly, MHC class I antigen expression was up
      regulated on the surface of cells transfected with the E7 siRNA, but not on that
      of untransfected cells. Taken together, our results demonstrate that the HPV16E7
      protein is associated with the MHC class I promoter and mediates MHC class I
      downregulation by repressing chromatin activation.

PMID- 16979589
TI  - Addition of electrophilic lipids to actin alters filament structure.
AB  - Pathophysiological processes associated with oxidative stress lead to the
      generation of reactive lipid species. Among them, lipids bearing unsaturated
      aldehyde or ketone moieties can form covalent adducts with cysteine residues and
      modulate protein function. Through proteomic techniques we have identified actin
      as a target for the addition of biotinylated analogs of the cyclopentenone
      prostaglandins 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) and PGA(1) in NIH-3T3
      fibroblasts. This modification could take place in vitro and mapped to the
      protein C-terminal end. Other electrophilic lipids, like the isoprostane 8-iso
      PGA(1) and 4-hydroxy-2-nonenal, also bound to actin. The C-terminal region of
      actin is important for monomer-monomer interactions and polymerization. Electron
      microscopy showed that actin treated with 15d-PGJ(2) or 4-hydroxy-2-nonenal
      formed filaments which were less abundant and displayed shorter length and
      altered structure. Streptavidin-gold staining allowed mapping of biotinylated 15d
      PGJ(2) at sites of filament disruption. These results shed light on the
      structural implications of actin modification by lipid electrophiles.

PMID- 16979590
TI  - Inhibition of HIV-1 replication by vesicular stomatitis virus envelope
      glycoprotein pseudotyped baculovirus vector-transduced ribozyme in mammalian
      cells.
AB  - The baculovirus has recently emerged as a promising vector for in vivo gene
      therapy. To investigate its potential as a delivery vector for an anti-virus
      ribozyme targeting HIV-1, we constructed recombinant baculovirus vectors bearing
      a ribozyme-synthesizing cassette driven by the tRNA(i)(Met) promoter with
      enhanced transduction efficiency by displaying vesicular stomatitis virus
      glycoprotein (VSV-G) on the viral envelope. Transduction of HeLa CD4(+) cells
      with a recombinant baculovirus delivering the HIV-1 U5 gene-specific ribozyme
      dramatically suppressed HIV-1 expression in this cell line. The VSV-G pseudotyped
      baculovirus vector-transduced ribozyme potently inhibited HIV-1 replication
      compared to a recombinant baculovirus vector-transduced ribozyme lacking VSV-G.
      The use of a baculovirus vector might be beneficial for application in gene
      therapy.

PMID- 16979591
TI  - Phosphorylation at Tyr-694 of Nogo-A by Src-family kinases.
AB  - Nogo-A is a neurite outgrowth inhibitor protein associated with myelin in the
      central nervous system. Unexpectedly, targeted disruption of Nogo-A in mice
      results in little or no improvement of axonal regeneration, suggesting that Nogo
      A has other functions and/or receives complex regulations to exert its inhibitory
      functions. Here, we have found that Nogo-A becomes phosphorylated at Tyr-694 in
      the N-terminal region. The phosphorylation is mediated co-operatively by Src
      family tyrosine kinases, which play many important roles in the nervous system.
      Levels of tyrosine phosphorylation of Nogo-A seem to be irrelevant to
      developmental stages of oligodendrocytes, and might be regulated by specific
      extracellular stimuli. Identification of tyrosine phosphorylation of Nogo-A will
      introduce an additional level of complexity into Nogo-A functions.

PMID- 16979592
TI  - Molecular basis of cellular localization of poly C binding protein 1 in neuronal
      cells.
AB  - Poly C binding protein 1 (PCBP) is involved in the transcriptional regulation of
      neuronal mu-opioid receptor gene. In this study, we examined the molecular basis
      of PCBP cellular/nuclear localization in neuronal cells using EGFP fusion
      protein. PCBP, containing three KH domains and a variable domain, distributed in
      cytoplasm and nucleus with a preferential nuclear expression. Domain-deletional
      analyses suggested the requirement of variable and KH3 domains for strong PCBP
      nuclear expression. Within the nucleus, a low nucleolar PCBP expression was
      observed, and PCBP variable domain contributed to this restricted nucleolar
      expression. Furthermore, the punctate nuclear pattern of PCBP was correlated to
      its single-stranded (ss) DNA binding ability, with both requiring cooperativity
      of at least three sequential domains. Collectively, certain PCBP domains thus
      govern its nuclear distribution and transcriptional regulatory activity in the
      nucleus of neurons, whereas the low nucleolar expression implicates the
      disengagement of PCBP in the ribosomal RNA synthesis.

PMID- 16979593
TI  - Regulation of IL-27p28 gene by lipopolysaccharide in dendritic DC2.4 cells.
AB  - To elucidate the regulation of IL-27p28 gene, we analyzed the promoter region of
      the gene in DC2.4 cells with or without lipopolysaccharide (LPS)-treatment. The
      results indicate that a region (-648 to -364) of p28 promoter was responsible for
      LPS-induction. EMSA with DNA probes within the region reveals that binding of
      GATA motif bound proteins was decreased by LPS-treatment. We identified one of
      the proteins as non-POU domain-containing octamer binding protein (NonO). Taken
      together, LPS-induced activation of IL-27p28 gene can be accounted for by the
      displacement of bound NonO protein from the IL-27p28 promoter.

PMID- 16979594
TI  - An efficient transgenic system by TA cloning vectors and RNAi for C. elegans.
AB  - In the nematode, transgenic analyses have been performed by microinjection of DNA
      from various sources into the syncytium gonad. To expedite these transgenic
      analyses, we solved two potential problems in this work. First, we constructed an
      efficient TA-cloning vector system which is useful for any promoter. By
      amplifying the genomic DNA fragments which contain regulatory sequences with or
      without the coding region, we could easily construct plasmids expressing
      fluorescent protein fusion without considering restriction sites. We could
      dissect motor neurons with three colors in a single animal. Second, we used
      feeding RNAi to isolate transgenic strains which express lag-2::venus fusion
      gene. We found that the fusion protein is toxic when ectopically expressed in
      embryos but is functional to rescue a loss of function mutant in the lag-2 gene.
      Thus, the transgenic system described here should be useful to examine the
      protein function in the nematode.

PMID- 16979595
TI  - ERK binds, phosphorylates InsP3 type 1 receptor and regulates intracellular
      calcium dynamics in DT40 cells.
AB  - Modulation on the duration of intracellular Ca(2+) transients is essential for B
      cell activation. We have previously shown that extracellular-signal-regulated
      kinase (ERK) can phosphorylate inositol 1,4,5-trisphosphate receptor type 1
      (IP(3)R1) at serine 436 and regulate its calcium channel activity. Here we
      investigate the potential physiological interaction between ERK and IP(3)R1 using
      chicken DT40 B-cell line in which different mutants are expressed. The
      interaction between ERK and IP(3)R1 is confirmed by co-immunoprecipitation and
      fluorescence resonance energy transfer (FRET) assays. This constitutive
      interaction is independent of either ERK kinase activation or IP(3)R1
      phosphorylation status. Back phosphorylation analysis further shows that type 1
      IP(3)R (IP(3)R1) is phosphorylated by ERK in anti-IgM-activated DT40 cells.
      Finally, our data show that the phosphorylation of Ser 436 in the IP(3)-binding
      domain of IP(3)R1 leads to less Ca(2+) release from endoplasmic reticulum (ER)
      microsomes and accelerates the declining of calcium increase in DT40 cells in
      response to anti-IgM stimulation.

PMID- 16979596
TI  - NMR structure determination of alpha-conotoxin BuIA, a novel neuronal nicotinic
      acetylcholine receptor antagonist with an unusual 4/4 disulfide scaffold.
AB  - We have determined a high-resolution three-dimensional structure of alpha
      conotoxin BuIA, a 13-residue peptide toxin isolated from Conus bullatus. Despite
      its unusual 4/4 disulfide bond layout alpha-conotoxin BuIA exhibits strong
      antagonistic activity at alpha6/alpha3beta2beta3, alpha3beta2, and alpha3beta4
      nAChR subtypes like some alpha4/7 conotoxins. alpha-Conotoxin BuIA lacks the C
      terminal beta-turn present within the second disulfide loop of alpha4/7
      conotoxins, having only a "pseudo omega-shaped" molecular topology. Nevertheless,
      it contains a functionally critical two-turn helix motif, a feature ubiquitously
      found in alpha4/7 conotoxins. Such an aspect seems mainly responsible for
      similarities in the receptor recognition profile of alpha-conotoxin BuIA to
      alpha4/7 conotoxins. Structural comparison of alpha-conotoxin BuIA with alpha4/7
      conotoxins and alpha4/3 conotoxin ImI suggests that presence of the second
      helical turn portion of the two-turn helix motif in alpha4/7 and alpha4/4
      conotoxins may be important for binding to the alpha3 and/or alpha6 subunit of
      nAChR.

PMID- 16979597
TI  - Mice lacking the gene encoding for MMP-9 and resistance artery reactivity.
AB  - OBJECTIVES: To define the link between the deletion of gene encoding for
      metalloproteinase 9 and resistance artery reactivity, we studied in vitro smooth
      muscle and endothelial cell function in response to pressure, shear stress, and
      pharmacological agents. BACKGROUND: Matrix metalloproteinases play a crucial role
      in the regulation of extracellular matrix turnover and structural artery wall
      remodeling. METHODS: Resistance arteries were isolated from mice lacking gene
      encoding for MMP-9 (KO) and their control (WT). Hemodynamic, pharmacology
      approaches, and Western blot analysis were used in this study. RESULTS: The
      measurement of blood pressure in vivo was similar in KO and WT mice. Pressure
      induced myogenic tone, contractions to angiotensin-II and phenylephrine were
      similar in both groups. The inhibition of MMP2/9 ((2R)-2-[(4-biphenylylsulfonyl)
      amino]-3-phenylpropionic acid) significantly decreased myogenic tone in WT and
      had no effect in KO mice. Relaxation endothelium-dependent (flow-induced-
      dilation 41.3+/-0.6 vs. 21+/-1.6 at 10 microl/min in KO and WT mice,
      respectively, P<0.05) and eNOS expression were increased in KO compared to WT
      mice. The inhibition of eNOS with L-NAME significantly decreased endothelium
      response to shear stress, which was more pronounced in KO mice resistance
      arteries (-26.83+/-2.5 vs. -15.84+/-2.3 at 10 microl/min in KO and WT,
      respectively, P<0.05). However, the relaxation to exogenous nitric oxide-donor
      was similar in both groups. CONCLUSION: Our study provides evidence of a
      selective effect of MMP-9 on endothelium function. Thus, MMP-9 gene deletion
      specifically increased resistance artery dilation endothelium-dependent and eNOS
      expression. Based on our results, MMP-9 could be a potential therapeutic target
      in cardiovascular disease associated with resistance arteries dysfunction.

PMID- 16979598
TI  - The co-treatments of vigabatrin and P2X receptor antagonists protect ischemic
      neuronal cell death in the gerbil hippocampus.
AB  - During transient global ischemia, the excessive accumulation of intracellular
      Ca2+ induced by several episodes triggers delayed neuronal death within the
      vulnerable CA1 region of the hippocampus after ischemia-reperfusion insults.
      Although P2X receptors provide an additional source of Ca2+ entry, little data
      are available that these receptors could modulate the performance of the ischemic
      neuronal death. Therefore, we investigated the roles of the P2X receptor in the
      ischemic neuronal damage associated with various sequelae of transient ischemia,
      and the effects of their antagonist on the ischemic insults. As the results,
      ischemic insults increased P2X receptor expression in the gerbil hippocampus.
      Neither vigabatrin (VGB) nor P2X receptor antagonists (suramin, pyridoxal
      phosphate-6-azophenyl-2',4'-disulfonic acid) protected against the delayed
      neuronal death in the CA1 region of the hippocampus after ischemia. However, the
      co-treatments of VGB and P2X receptor antagonists effectively prevent ischemia
      induced neurodegeneration. Therefore, these findings suggest that blockade of the
      P2X receptor accompanied by activation of GABAergic inhibition may play an
      important role in the neuroprotection against ischemic insults.

PMID- 16979599
TI  - A 3D model of Reelin subrepeat regions predicts Reelin binding to carbohydrates.
AB  - Reelin is a large molecule of the extracellular matrix (ECM) which regulates
      neuronal positioning during the early stages of cortical development in
      vertebrate species. The Reelin molecule can be subdivided into a smaller N
      terminal domain, showing homology with F-spondin, and a larger C-terminal region
      containing 8 EGF-like repeats. The localization of Reelin in the ECM, its large
      dimensions and the modular organization of its primary structure led us to
      suppose a structure of its modules similar to domains commonly found in ECM
      proteins such as Agrin, laminins and thrombospondins. We therefore performed a
      sequence alignment and molecular modeling analysis to study the three-dimensional
      fold of the Reelin subrepeat regions. Our analysis produces a tentative model of
      the core region of the Reelin subrepeat sequences and suggests the presence in
      this 3D model of structural features common to polysaccharide-binding modules
      which are often found on proteoglycans of the ECM. These findings provide a
      conceptual framework for further experiments aimed at testing the functions of
      the EGF-like repeat regions of Reelin.

PMID- 16979601
TI  - Regulation of forebrain GABAergic stress circuits following lesion of the ventral
      subiculum.
AB  - Ventral subiculum (vSUB) lesions enhance corticosterone responses to psychogenic
      stressors via trans-synaptic influences on paraventricular nucleus (PVN) neurons.
      Synaptic relays likely occur in GABA-rich regions interconnecting the vSUB and
      PVN. The current study examines whether vSUB lesions compromise stress-induced c
      fos induction and GABA biosynthetic capacity in putative limbic-hypothalamic
      stress relays. Male Sprague-Dawley rats received bilateral ibotenate or sham
      lesions of the vSUB. Animals were divided into two groups, with one group
      receiving exposure to novelty stress and the other left unstressed. Exposure to
      novelty stress increased c-fos mRNA expression in the PVN to a greater degree in
      vSUB lesion relative to shams, consistent with an inhibitory role for the vSUB in
      the HPA stress response. However, c-fos induction was not affected in other
      forebrain GABAergic stress pathways, such as the lateral septum, medial preoptic
      area or dorsomedial hypothalamus. vSUB lesions increased GAD65 or GAD67 mRNA
      levels in several efferent targets, including anterior and posterior subnuclei of
      the bed nucleus of the stria terminalis and lateral septum. Lesions did not
      effect stress-induced increases in GAD65 expression in principal output nuclei of
      the amygdala. The current data suggest that loss of vSUB innervations produces a
      compensatory increase in GAD expression in subcortical targets; however, this up
      regulation is insufficient to block lesion-induced stress hyperresponsiveness,
      perhaps driven by amygdalar disinhibition of the PVN.

PMID- 16979600
TI  - Expression of hyperpolarization-activated cyclic nucleotide-gated cation channels
      in rat dorsal root ganglion neurons innervating urinary bladder.
AB  - Afferent pathways innervating the urinary bladder consist of myelinated Adelta-
      and unmyelinated C-fibers, the neuronal cell bodies of which correspond to medium
      and small-sized cell populations of dorsal root ganglion (DRG) neurons,
      respectively. Since hyperpolarization-activated cyclic nucleotide-gated cation
      (HCN) channel currents have been identified in various peripheral sensory
      neurons, we examined the expression of isoforms of HCN channels in the L6-S1
      spinal cord and bladder afferent neurons from L6-S1 DRG in rats. Among HCN-1, HCN
      2 and HCN-4 channel subtypes, positive staining with HCN-2 antibodies was found
      in the superficial dorsal horn of the spinal cord and small- and medium-sized
      unidentified DRG neurons. In dye-labeled bladder afferent neurons, HCN-2-positive
      cells were found in approximately 60% of neurons, and HCN-2 was expressed in both
      small- and medium-sized neurons with a higher ratio (expression ratio: 61% and
      50% of neurons, respectively) compared with unidentified DRG neurons, in which
      the HCN expression ratio was 47% and 21% of small- and medium-sized cells,
      respectively. These results suggest that HCN-2 is the predominant subtype of HCN
      channels, which can control neuronal excitability, in small-sized C-fiber and
      medium-sized Adelta fiber DRG neurons including bladder afferent neurons, and
      might modulate activity of bladder afferent pathways controlling the micturition
      reflex.

PMID- 16979602
TI  - Structural analysis of a unique hybrid-type ganglioside with isoglobo-, neolacto
      , and ganglio-core from the gills of the Pacific salmon (Oncorhynchus keta).
AB  - Monosialosyl gangliosides from the gills of the Pacific salmon, Oncorhynchus
      keta, have been prepared by solvent extraction and DEAE-Sephadex column
      chromatography. The unknown acidic glycolipids (M14 and M15) with slower mobility
      than GM1a on thin-layer chromatography were separated by Iatrobeads column
      chromatography and were characterized by compositional analysis, methylation
      analysis, chemical, and enzymatic degradation, negative-ion LSIMS, and (1)H
      nuclear magnetic resonance spectroscopy. Both M14 and M15 contained a same
      oligosaccharide core with isoglobo-, neolacto-, and ganglio-series as follows:
      [carbohydrate structure: see text]. The only difference between M14 and M15 was
      in fatty acid acylation. Analysis of the fatty acids indicated a predominance of
      C24:1 fatty acid in M14 and shorter chain saturated fatty acids, C14:0 and C16:0,
      in M15.

PMID- 16979603
TI  - FCCP is cardioprotective at concentrations that cause mitochondrial oxidation
      without detectable depolarisation.
AB  - OBJECTIVE: The role of mitochondria and in particular of mitochondrial uncoupling
      in the mechanism of cardioprotection is not defined. In the accompanying paper we
      have shown that pretreatment of isolated rat hearts with a low concentration (100
      nM) of FCCP, prior to global ischaemia, is cardioprotective, while 300 nM FCCP
      exacerbates injury. Here we define the mitochondrial responses to increasing
      concentrations of FCCP and also to explore the equivalence of the
      cardioprotective doses of diazoxide. METHODS: Changes in mitochondrial
      respiration in response to FCCP and diazoxide were determined in isolated rat
      ventricular myocytes. In addition, mitochondrial state was monitored using
      confocal microscopy to record mitochondrial potential (TMRM) and redox state
      (NADH) during FCCP and diazoxide treatment. Myocytes were also voltage-clamped
      and whole cell currents recorded in response to 100 nM FCCP. RESULTS: FCCP (10
      1000 nM) caused significant dose-dependent increase in oxygen consumption.
      Diazoxide (30 microM) failed to cause any measurable change in mitochondrial
      function. FCCP at 100 nM caused mitochondrial oxidation, but no change in
      mitochondrial membrane potential or (sarc)K(ATP) channel current, while at 300
      nM, FCCP caused significant mitochondrial depolarisation. Diazoxide failed to
      induce any mitochondrial oxidation or depolarisation. CONCLUSIONS: Concentrations
      of FCCP that cause mitochondrial oxidation without depolarisation are
      cardioprotective. Higher FCCP concentrations dissipate mitochondrial membrane
      potential and exacerbate injury. This establishes the principle that mild
      mitochondrial uncoupling activates a protective mechanism. Diazoxide did not
      cause mitochondrial oxidation or mitochondrial depolarisation, suggesting it
      induces protection via another mechanism.

PMID- 16979604
TI  - Cardiovascular benefits of omega-3 fatty acids.
AB  - Cardiac societies recommend the intake of 1 g/day of the two omega-3 fatty acids
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for cardiovascular
      disease prevention, treatment after a myocardial infarction, prevention of sudden
      death, and secondary prevention of cardiovascular disease. These recommendations
      are based on a body of scientific evidence that encompasses literally thousands
      of publications. Of four large scale intervention studies three also support the
      recommendations of these cardiac societies. One methodologically questionable
      study with a negative result led a Cochrane meta-analysis to a null conclusion.
      This null conclusion, however, has not swayed the recommendations of the cardiac
      societies mentioned, and has been refuted with good reason by scientific
      societies. Based on the scientific evidence just mentioned, we propose a new risk
      factor to be considered for sudden cardiac death, the omega-3 index. It is
      measured in red blood cells, and is expressed as a percentage of EPA + DHA of
      total fatty acids. An omega-3 index of >8% is associated with 90% less risk for
      sudden cardiac death, as compared to an omega-3 index of <4%. The omega-3 index
      as a risk factor for sudden cardiac death has striking similarities to LDL as a
      risk factor for coronary artery disease. Moreover, the omega-3 index reflects the
      omega-3 fatty acid status of a given individual (analogous to HbA1c reflecting
      glucose homeostasis). The omega-3 index can therefore be used as a goal for
      treatment with EPA and DHA. As is the case now for LDL, in the future, the
      cardiac societies might very well recommend treatment with EPA and DHA to become
      goal oriented (e.g. an omega-3 index>8%).

PMID- 16979605
TI  - IgE isotype switch and IgE production are enhanced in IL-21-deficient but not IFN
      gamma-deficient mice in a Th2-biased response.
AB  - IgE plays a critical role in the pathogenesis of allergy and asthma. Therefore,
      suppression of IgE production would provide therapeutic benefits to patients
      suffering from these diseases. We have reported that the production of IgE is
      regulated differently in the spleen vs. the draining lymph nodes (LN). IgE
      isotype switch and IgE producing B cell expansion occur in the draining LN after
      antigen (Ag) immunization, but do not happen in the spleen. In addition, a
      population of pre-existing IgE+ cells is observed in the spleen of normal or sham
      immunized mice, but is not present in the draining LN. To further understand the
      regulation of IgE production in different lymphoid organs, and the potential
      inhibitory factors of IgE isotype switch in the spleen, the involvement of IL-21
      and IFN-gamma in regulating IgE production was investigated by using the IL-21
      and the IFN-gamma deficient mice. We found that in the absence of IL-21 IgE
      isotype switch and IgE+ cell clonal expansion were dramatically enhanced in the
      spleen and IgE isotype switch was partially increased in the draining LN. In
      addition, IgE production of the pre-existing CD19-CD5+B220(low) IgE+ cells in the
      spleen was also increased in the absence of IL-21 under physiological conditions.
      In contrast, using the IFN-gamma deficient mice, we did not observe a negative
      impact of IFN-gamma on either IgE isotype switch or IgE production. Our data
      suggest that IL-21 appears to be a critical cytokine to keep low IgE levels under
      physiological and pathological conditions.

PMID- 16979606
TI  - Glycerol-derived ester oligomers from cork suberin.
AB  - The cork suberin polyester was partially depolymerized by a methanolysis reaction
      catalyzed by calcium hydroxide. The methanolisate was analysed by ESI-MS/MS in
      the form of [M+Li](+) adduct-ions. This reaction solubilized a mixture of
      monomers and oligomers, including a set of glycerol-derived dimeric and trimeric
      esters. Four types of glycerol esters were identified: monoacylglycerols of
      alpha,omega-diacids, of omega-hydroxyacids and of monoacids; diglycerol diesters
      of alpha,omega-diacids; diacylglycerols of alpha,omega-diacids; monoacylglycerols
      of linear dimeric esters of alpha,omega-diacids and omega-hydroxyacids. The
      alpha,omega-diacids and omega-hydroxyacids found as monomer residues in the
      glycerol esters are the main ones found as cork suberin monomers. It is concluded
      that suberin is a glycerol-derived lipid of polymeric dimensions. Due to the
      protective and insulating role that it plays in plants, suberin should be
      considered together with the other known glycerolipids that build up biological
      membranes.

PMID- 16979607
TI  - Interference of ceftriaxone on capillary zone electrophoresis.

PMID- 16979608
TI  - Prevalence of chronic kidney disease in a middle and old-aged population of
      Beijing.

PMID- 16979609
TI  - Resonance scattering spectra of micrococcus lysodeikticus and its application to
      assay of lysozyme activity.
AB  - BACKGROUND: Several methods, including turbidimetric and colorimetric methods,
      have been reported for the detection of lysozyme activity. However, there is no
      report about the resonance scattering spectral (RSS) assay, which is based on the
      catalytic effect of lysozyme on the hydrolysis of micrococcus lysodeikticus (ML)
      and its resonance scattering effect. METHODS:  RESULTS: ML has 5 resonance
      scattering peaks at 360 400, 420, 470, and 520 nm with the strongest one at 470
      nm. The concentration of ML in the range of 2.0x10(6)-9.3x10(8) cells/ml is
      proportional to the RS intensity at 470 nm (I(470 nm)). A new catalytic RSS
      method has been proposed for 0.24-40.0 U/ml (or 0.012-2.0 mug/ml) lysozyme
      activity, with a detection limit (3sigma) of 0.014 U/ml (or 0.0007 microg/ml).
      Saliva samples were assayed by this method, and it is in agreement with the
      results of turbidimetric method. The slope, intercept and the correlation
      coefficient of the regression analysis of the 2 assays were 0.9665, -87.50, and
      0.9973, respectively. CONCLUSION: The assay has high sensitivity and simplicity.

PMID- 16979610
TI  - Multiple myeloma associated with sialyl salivary-type amylase.
AB  - BACKGROUND: There have been several reports describing a notable hyperamylasaemia
      in patients with multiple myeloma. Such amylase-producing myelomas have been
      mainly described in the context of concomitant salivary-type hyperamylasaemia,
      with sialyl salivary-type amylase identified in a portion of those cases. We
      investigated the incidence of the production of sialyl salivary-type amylase in
      serum of multiple myeloma patients. METHODS: Eleven patients (6 male and 5
      female) who had been diagnosed as having multiple myeloma were enrolled in this
      study. Sialyl salivary-type amylase was detected by isoamylase electrophoresis
      and HPLC analysis, and identified by detecting either abnormal neuraminidase
      sensitive band through isoamylase electrophoresis or abnormal extra-elution peak
      of amylase by means of HPLC analysis. RESULTS: Sialyl salivary-type amylase was
      detected in 7 out of 11 (63.6%) patients. Median total amylase activity was 154
      U/l (range 109-43020). Isoamylase electrophoretic patterns of patients' serum
      were normal in 5 patients (71.4%) out of 7 patients and salivary-dominant in 2
      (50.0%) out of 4 patients. CONCLUSIONS: We consider that there is no significant
      relationship between total serum amylase level and amylase isoenzyme pattern in
      the incidence of production of sialyl salivary-type amylase with multiple
      myeloma.

PMID- 16979611
TI  - HMGB1, a novel inflammatory cytokine.
AB  - High mobility group box 1 (HMGB1) exhibits unique biochemical functions as a
      biologically intrinsic requisite factor and as a toxin. As such, it is imperative
      to understand the mechanism by which these seemingly and diametrically opposed
      functions are exerted. To effectively discriminate these actions is important to
      accurately and precisely determine the concentration of HMGB1 in biological
      samples. Research in this fascinating field, however, has been lacking due to the
      absence of a simple analytical system for HMGB1 that can be adapted for large
      sample numbers. In this report, we review the physiological and pathological
      significance of HMGB1 and describe the development of an assay method for this
      pleiotropic protein.

PMID- 16979612
TI  - The changes in NT-proBNP plasma concentrations during dialysis are highly
      dependent of the dialysis membrane ultrafiltration coefficient.
AB  - BACKGROUND: NT-proBNP is a powerful marker with diagnostic and pronostic value
      for heart failure. It is of particular interest in patients with end-stage renal
      disease who are at high risk for heart failure. The aim of this study was to
      investigate the effect of hemodialysis on plasma NT-proBNP concentrations.
      METHODS: NT-proBNP concentration was measured in 67 patients before and after
      hemodialysis. RESULTS: In the 20 patients dialyzed with a membrane whose
      ultrafiltration coefficient was below or equal to12, NT-proBNP concentration was
      comparable after and before dialysis (16611+/-21024 vs. 15216+/-19027 pg/ml, NS).
      At the opposite, in the 47 patients dialyzed with a membrane whose
      ultrafiltration coefficient was above or equal to 40, NT proBNP concentration was
      35% lower after dialysis compared to before dialysis (11983+/-21819 vs. 18574+/
      31862 pg/ml, p<0.0001). CONCLUSIONS: In patients dialyzed with a membrane whose
      ultrafiltration coefficient is high, dialysis is likely to decrease results by
      one third. Thus sampling blood before dialysis in hemodialyzed patients appears
      as the best time to stratify the cardiovascular risk in these patients.

PMID- 16979613
TI  - Comparison of glutathione S-transferase-Pi expression at mRNA levels in
      oesophageal mucosa using RT-PCR-ELISA in individuals with reflux diseases,
      adenocarcinoma and squamous cell carcinoma.
AB  - OBJECTIVES: To develop a RT-PCR technique coupled with Enzyme Linked Immunosobant
      Assay (ELISA) i.e. RT-PCR-ELISA for measurement of class-Pi glutathione S
      transferase (GST-P)-specific mRNA in esophageal diseases. METHODS: In this study,
      66 esophageal tissue biopsies diagnosed as non-erosive reflux disease (NERD),
      gastroesophageal reflux disease (GERD), adenocarcinoma (ADC), and squamous cell
      carcinoma (SCC) were used. Standardization of the RT-PCR-ELISA was carried out
      using specific GST-Pi and beta-actin primers, biotin labeled probe, DIG-labeling
      RT-PCR and anti-DIG-HRP conjugate. RESULTS: The results of RT-PCR-ELISA based on
      OD ratio of GST-Pi mRNA/beta-actin showed that there was no significant
      difference in GST-Pi expression in normal, NERD and GERD samples. Overexpression
      of GST-Pi in malignant tissues (ADC and SCC) was distinguishable. The OD ratio of
      GST-Pi mRNA expression to beta-actin mRNA was 1.17+/-0.13 and 1.3+/-0.13 in ADC
      and SCC samples, respectively, which is significantly higher (P<0.05) than
      matching control (0.78+/-0.06 and 0.85+/-0.07). CONCLUSIONS: RT-PCR-ELISA showed
      that GST-Pi expression was not altered in GERD and NERD esophagus, whereas, in
      ADC and SCC samples, it was significantly higher (P<0.05) as compared to inflamed
      and normal tissues.

PMID- 16979614
TI  - Natremia of healthy term newborns at 48 h of life: influence of feeding patterns.
AB  - OBJECTIVES: To describe natremia in healthy term newborns and determine whether
      there is a relationship between blood sodium and feeding patterns. METHODS: All
      normal newborns, admitted to the nursery between January and March 2004 were
      eligible for this prospective cohort study. Inclusion criteria were: > or =37
      weeks of gestational age, birth weight > or =2500 g, Apgar scores > or =7 at 5
      and 10 min and normal physical examination. A capillary blood sample was taken at
      48+/-12 h of life. RESULTS: Blood samples from 126 newborns were analyzed. Mean
      gestational age was 39.6 weeks, birth weight was 3414 g and weight loss at 48 h
      of life was 6.5% of birth weight. Mean capillary blood sodium was 141 mmol/L (SD
      3.4). Exclusively, breast-fed newborns had statistically higher mean blood sodium
      (141 mmol/L, SD 3.0) than the non-exclusively breast-fed+formula fed group (139
      mmol /L, SD 3.7). There was a significant linear association between blood sodium
      and the quantity of milk supplements received as well as between blood sodium and
      weight loss. CONCLUSIONS: Most newborns have blood sodium values within a
      narrower range than previously described in the literature. We also demonstrate
      that the exclusively breast-fed infants appear to have marginally but
      statistically higher values of blood sodium than non-exclusively breast-fed and
      formula-fed infants.

PMID- 16979615
TI  - Determination of free and total carnitine in plasma by an enzymatic reaction and
      spectrophotometric quantitation spectrophotometric determination of carnitine.
AB  - OBJECTIVES: Carnitine initiates the beta-oxidation of fatty acids and its
      deficiency is a problem in several metabolic diseases. This work describes a
      validated quick and simple enzymatic assay for the determination of free and
      total carnitine in plasma. METHODS: Carnitine reacts with acetyl-CoA catalized by
      carnitine acetyltransferase. The coenzyme A liberated combines with 5,5'
      dithiobis-(2-nitrobenzoic acid) and forms thiophenolate ion, measured
      spectrophotometrically at 412 nm. The method requires precipitation of proteins
      and the alkaline hydrolysis of acylcarnitines for total carnitine. RESULTS: The
      detection limit is 1.7 micromol/L in plasma and inter- and intra-day imprecision
      is less than 5%. The recovery of spiked plasma samples is 97%. The method was
      tested with an inter-laboratory assay, yielding excellent correlation
      (r(2)=0.994), and it was applied to the determination of normal values of
      carnitine in plasma. CONCLUSIONS: A reliable spectrophotometric method has been
      validated with very good precision, with simple instrumental and easy sample
      preparation.

PMID- 16979616
TI  - Application of the EMIT 2000 Tacrolimus assay on the Abbott Architect c8000 high
      volume clinical chemistry analyzer.
AB  - OBJECTIVES: Evaluation of the performance of the EMIT 2000 Tacrolimus assay on
      the Abbott Architect c8000 analyzer. DESIGN AND METHODS: Imprecision studies were
      performed and patient samples were assayed by EMIT assay and by LC-MS/MS.
      RESULTS: Limit of quantification was established at 2.8 microg/L. A positive bias
      of 17.5% between results measured on EMIT and on LC-MS/MS was detected.
      CONCLUSIONS: EMIT 2000 Tacrolimus assay is suitable for automated analyses of
      Tacrolimus on the Architect c8000.

PMID- 16979617
TI  - Evidence for a reduced transcriptional state during hibernation in ground
      squirrels.
AB  - During mammalian hibernation, metabolic rate can be reduced to <5% of the
      euthermic rate as a result of coordinated suppression of multiple energy
      expensive metabolic processes. Gene transcription is one of these and the present
      study examines mechanisms of transcriptional control that could contribute to
      lowering the rate of gene expression in torpor. Histone deacetylases (HDAC) have
      been linked to gene silencing and measured HDAC activity was 1.82-fold higher in
      skeletal muscle of hibernating thirteen-lined ground squirrels, Spermophilus
      tridecemlineatus, compared with euthermic controls. Western blotting also showed
      that HDAC1 and HDAC4 protein levels were 1.21-and 1.48-fold higher, respectively,
      in muscle from torpid animals. Histone H3 was also evaluated by Western blotting.
      Total histone H3 was unchanged but two forms of covalently modified histone H3
      that are associated with active transcription (phosphorylated Ser 10 and
      acetylated Lys 23) were significantly reduced by 38-39% in muscle during
      hibernation. Finally, RNA polymerase II activity was measured using a PCR-based
      approach; activity in muscle from hibernating squirrels was only 57% of the
      euthermic value. These data support an overall decrease in transcriptional
      activity in skeletal muscle of hibernating animals that is accomplished by
      multiple molecular mechanisms.

PMID- 16979618
TI  - Pax6 controls cerebral cortical cell number by regulating exit from the cell
      cycle and specifies cortical cell identity by a cell autonomous mechanism.
AB  - Many cerebral cortical neurons and glia are produced by apical progenitors
      dividing at the ventricular surface of the embryonic dorsal telencephalon. Other
      neurons are produced by basal progenitor cells, which are derived from apical
      progenitors, dividing away from the ventricular surface. The transcription factor
      Pax6 is expressed in apical progenitors and is downregulated in basal
      progenitors, which upregulate the transcription factor Tbr2. Here we show that
      Pax6(-/-) cells are under-represented in the cortex of Pax6(+/+)<-->Pax6(-/-)
      chimeras early in corticogenesis, indicating that Pax6 is required for the
      production of normal numbers of cortical cells. We provide evidence that this
      underproduction is attributable to an early depletion of the progenitor pool
      caused by greater than normal proportions of newly divided cells exiting the cell
      cycle. We show that most progenitor cells dividing away from the ventricular
      surface in Pax6(-/-) embryos fail to express the transcription factor Tbr2 and
      that Pax6 is required cell autonomously for Tbr2 expression in the developing
      cortex of Pax6(+/+)<-->Pax6(-/-) chimeras. Transcription factors normally
      expressed ventrally in the telencephalic ganglionic eminences (Mash1, Dlx2 and
      Gsh2) are upregulated cell autonomously in mutant cells in the developing cortex
      of Pax6(+/+)<-->Pax6(-/-) chimeras; Nkx2.1, which is expressed only in the medial
      ganglionic eminence, is not. These data indicate that early functions of Pax6 in
      developing cortical cells are to repress expression of transcription factors
      normally found in the lateral ganglionic eminence, to prevent precocious
      differentiation and depletion of the progenitor pool, and to induce normal
      development of cortical basal progenitor cells.

PMID- 16979619
TI  - Chromatin immunoprecipitation reveals a novel role for the Drosophila SoxNeuro
      transcription factor in axonal patterning.
AB  - In all metazoans, the expression of group B HMG domain Sox transcription factors
      is associated with the earliest stages of CNS development. In Drosophila,
      SoxNeuro (SoxN) is involved in dorso-ventral patterning of the neuroectoderm, and
      in the formation and segregation of neuroblasts. In this report, we show that
      SoxN expression persists in a subset of neurons and glial cells of the ventral
      nerve cord at embryonic stages 15/16. In an attempt to address SoxN function in
      late stages of CNS development, we have used a chromatin immunoprecipitation
      approach to isolate genomic regions bound in vivo by SoxN. We identified several
      genes involved in the regulation of axon scaffolding as potential direct target
      genes of SoxN, including beat1a, semaphorin2a, fasciclin2, longitudinal lacking
      and tailup/islet. We present genetic evidence for a direct involvement of SoxN in
      axonal patterning. Indeed, overexpressing a transcriptionally hyperactive mutated
      SoxN protein in neurons results in specific defects in axon scaffolding, which
      are also observed in transheterozygous combinations of SoxN null mutation and
      mutations in its target genes.

PMID- 16979620
TI  - Effects of 3-aminobenzamide, an inhibitor of poly (ADP-ribose) polymerase, in a
      mouse model of acute pancreatitis induced by cerulein.
AB  - Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks
      in DNA, plays an important role in the colon injury associated with experimental
      colitis. The aim of the present study was to examine the effects of 3
      aminobenzamide (3-AB), an inhibitor of PARP activity, in the development of acute
      pancreatitis caused by cerulein in mice. Intraperitoneal injection of cerulein in
      mice resulted in severe, acute pancreatitis characterized by oedema, neutrophil
      infiltration and necrosis and elevated serum levels of amylase and lipase.
      Infiltration of pancreatic and lung tissue with neutrophils (measured as increase
      in myeloperoxidase activity) was associated with enhanced expression of the
      intercellular adhesion molecule-1 (ICAM-1) and P-selectin. Immunohistochemical
      examination demonstrated a marked increase in the staining (immunoreactivity) for
      transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor
      (VEGF) in the pancreas of cerulein-treated mice in comparison to sham-treated
      mice. Acute pancreatitis in vehicle-treated mice was also associated with a
      significant mortality (40% survival at 5 days after cerulein administration). In
      contrast, (1) the degree of pancreatic inflammation and tissue injury
      (histological score), (2) upregulation/formation of ICAM-1 and P-selectin, (4)
      neutrophils infiltration and (5) the expression of TGF-beta and VEGF was markedly
      reduced in pancreatic tissue obtained from cerulein-treated mice which have been
      treated with 3-AB. These findings provide the evidence that PARP inhibition
      reduce the degree of pancreas injury caused by acute pancreatitis induced by
      cerulein administration.

PMID- 16979622
TI  - Increased iron deposition in rat liver fibrosis induced by a high-dose injection
      of dimethylnitrosamine.
AB  - Using a developed rat model of hepatic necrosis and subsequent fibrosis induced
      by a high-dose intraperitoneal injection of dimethylnitrosamine (DMN), we studied
      iron deposition and expression of transforming growth factor-beta(1) (TGF
      beta(1)) during the development of persistent liver fibrosis. Rats were
      sacrificed at several timepoints from 6 h to 10 months post-injection and the
      livers were examined for iron content and distribution, and for expression of
      alpha-smooth muscle actin, ED-1, TGF-beta(1), and collagen (alpha(2))I.
      Morphologic evidence of acute submassive hemorrhagic necrosis peaked at 36 h; on
      day 3 the residual parenchyma contained activated hepatic stellate cells (HSCs)
      and necrotic areas contained numerous macrophages; and on day 5, necrotic tissues
      and erythrocytes had been phagocytosed and macrophages contained abundant iron
      deposits. From days 7 to 10, iron-laden macrophages and activated HSCs
      (myofibroblasts) populated the fibrous septa in parallel. From week 2 to month
      10, closely arranged macrophages and myofibroblasts were found in central-to
      central bridging fibrotic tissue. TGF-beta(1) was strongly detected in both
      macrophages and HSCs during development of liver fibrosis. Our data suggest that
      increased iron deposition may be involved in the initiation and perpetuation of
      rat liver fibrosis. Iron-laden macrophages may influence HSCs through the action
      of TGF-beta(1) in DMN-induced liver fibrosis.

PMID- 16979621
TI  - MEN15596, a novel nonpeptide tachykinin NK2 receptor antagonist.
AB  - The pharmacological profile of MEN15596 or (6-methyl-benzo[b]thiophene-2
      carboxylic acid [1-(2-phenyl-1R-{[1-(tetrahydropyran-4-ylmethyl)-piperidin-4
      ylmethyl]-carbamoyl}-ethylcarbamoyl)-cyclopentyl]-amide), a novel potent and
      selective tachykinin NK2 receptor antagonist endowed with oral activity, is
      described. At the human recombinant tachykinin NK2 receptor, MEN15596 showed
      subnanomolar affinity (pKi 10.1) and potently antagonized (pKB 9.1) the
      neurokinin A-induced intracellular calcium release. MEN15596 selectivity for the
      tachykinin NK2 receptor was assessed by binding studies at the recombinant
      tachykinin NK1 (pKi 6.1) and NK3 (pKi 6.4) receptors, and at a number of 34
      molecular targets including receptors, transporters and ion channels. In isolated
      smooth muscle preparations MEN15596 showed a marked species selectivity at the
      tachykinin NK2 receptor with the highest antagonist potency in guinea-pig colon,
      human and pig bladder (pKB 9.3, 9.2 and 8.8, respectively) whereas it was three
      orders of magnitude less potent in the rat and mouse urinary bladder (pKB 6.3 and
      5.8, respectively). In agreement with binding experiments, MEN15596 showed low
      potency in blocking selective NK1 or NK3 receptor agonist-induced contractions of
      guinea-pig ileum preparations (pA2<or=6). In anaesthetized guinea-pigs, MEN15596
      inhibited in a dose-related and persistent manner colon contractions induced by
      the selective tachykinin NK2 receptor agonist, [betaAla8]neurokinin A(4-10) (3
      nmol/kg i.v.), either after intravenous (ED50 0.18 micromol/kg), intraduodenal
      (ED50 3.16 micromol/kg) or oral administration (10-30 micromol/kg) without
      affecting, at 3 micromol/kg, i.v., the colonic contractions produced by the NK1
      receptor selective agonist [Sar9]substance P sulfone (3 nmol/kg i.v.). In
      addition MEN15596 was effective in inhibiting bronchoconstriction produced by
      i.v. administration of [betaAla8]neurokinin A(4-10). Overall the results indicate
      that MEN15596 is a potent and selective tachykinin NK2 receptor antagonist
      possessing high affinity and potency for guinea-pig, pig and human receptor, long
      duration of action in in vivo experiments and good oral bioavailability.

PMID- 16979623
TI  - Pharmacological vascular reactivity in isolated diabetic rabbit ciliary artery.
AB  - Impairment of the ocular circulation induced by diabetes mellitus has not been
      fully defined, but is thought to be related to hemodynamic changes in the ocular
      circulation. The purpose of the present study is to investigate the functional
      and morphological changes occurring in the ciliary artery wall of rabbits with
      alloxan-induced diabetes mellitus. A single intravenous bolus injection of
      alloxan (100 mg/kg) was given to each of 26 10-week-old rabbits and 16 sham
      injected control rabbits. Twenty weeks later, control rabbits and diabetic
      rabbits were sacrificed, and their ciliary arteries were mounted in a myograph
      system. The responses of these arteries to high K+ solution (K-Krebs solution),
      phenylephrine and carbachol were investigated using isometric tension recording.
      L-NAME (NG-nitro-l-arginine methyl ester; 100 microM) and indomethacin (1 microM)
      were also used to test the mechanism causing the carbachol induced relaxation.
      The arteries were also examined morphologically. The maximum tensions induced by
      K-Krebs solution in this tissue were not significantly different: 17.2+/-0.8 mN
      (n=16) in the control rabbits and 17.6+/-0.8 mN (n=23) in the diabetic rabbits
      (P=0.36). Phenylephrine caused dose-dependent contraction with EC50 values of
      1.3+/-0.4 microM (n=6) in the control and 5.1+/-2.3 microM (n=6) in the diabetic
      rabbits, but there was no significant difference between the two (P=0.36).
      Carbachol induced dose-dependent relaxations in segments precontracted with K
      Krebs solution. These relaxations were significantly reduced in the diabetic
      rabbits. The maximum relaxation induced by carbachol was 77.0+/-2.4% (10 microM)
      and 66.4+/-2.5% (100 microM) in the control and diabetic rabbits, respectively.
      These values were significantly different (P=0.0076). The IC(50) value for
      carbachol was 396.3+/-58.4 nM (n=16) in the control, and 443.6+/-141.1 nM (n=23)
      in the diabetic rabbit (P=0.87). Application of a 100 microM nitric oxide
      synthase inhibitor, L-NAME, significantly inhibited the amplitude of relaxations
      evoked by carbachol (P=0.0066). However, these relaxations were not inhibited by
      pretreatment with 1 microM indomethacin (P=0.60). Histologically, the frequency
      of invaginations was less in the diabetic arterioles with a flattening of the
      lamina in the diabetic rabbits than in the controls. The cytoplasm of endothelial
      cells contained large vacuoles, indicating weak adhesion to the lamina. Some
      endothelial cells even showed vacuolar degeneration due to breakdown of the cell
      membranes. However, the smooth muscle cells were well preserved in the diabetic
      rabbit. These results suggest that the mechanism of impairment of ocular
      circulation induced by diabetes mellitus is mainly the reduction of NO synthase
      due to endothelial cell dysfunction. Furthermore, the characteristics of rabbits
      with alloxan-induced diabetes mellitus probably make them a useful model for
      investigating ocular complications induced by diabetic mellitus.

PMID- 16979624
TI  - The intracellular domain of the human protocadherin hFat1 interacts with Homer
      signalling scaffolding proteins.
AB  - The cadherin superfamily protein Fat1 is known to interact with the EVH1 domain
      of mammalian Ena/VASP. Here we demonstrate that: (i) the scaffolding proteins
      Homer-3 and Homer-1 also interact with the EVH1 binding site of hFat1 in vitro,
      and (ii) binding of Homer-3 and Mena to hFat1 is mutually competitive. Endogenous
      Fat1 binds to immobilised Homer-3 and endogenous Homer-3 binds to immobilised
      Fat1. Both, endogenous and over-expressed Fat1 exhibit co-localisation with Homer
      3 in cellular protrusions and at the plasma membrane of HeLa cells. As Homer
      proteins and Fat1 have been both linked to psychic disorders, their interaction
      may be of patho-physiological importance.

PMID- 16979625
TI  - Directed evolution of a bacterial efflux pump: adaptation of the E. coli TolC
      exit duct to the Pseudomonas MexAB translocase.
AB  - Bacterial multidrug efflux pumps operate by periplasmic recruitment and opening
      of TolC family outer membrane exit ducts by cognate inner membrane translocases.
      Directed evolution of active hybrid pumps was achieved by challenging a library
      of mutated, shuffled TolC variants to adapt to the non-cognate Pseudomonas MexAB
      translocase, and confer resistance to the efflux substrate novobiocin. Amino acid
      substitutions in MexAB-adapted TolC variants that endowed high resistance were
      recreated independently, and revealed that MexAB-adaptation was conferred only by
      substitutions located in the lower alpha-helical barrel of TolC, specifically the
      periplasmic equatorial domain and entrance coiled coils. These changes converge
      to the native MexAB partner OprM, and indicate an interface key to the function
      and diversity of efflux pumps.

PMID- 16979626
TI  - Molecular mechanism of 'mitocan'-induced apoptosis in cancer cells epitomizes the
      multiple roles of reactive oxygen species and Bcl-2 family proteins.
AB  - Mitochondria have emerged recently as effective targets for novel anti-cancer
      drugs referred to as 'mitocans'. We propose that the molecular mechanism of
      induction of apoptosis by mitocans, as exemplified by the drug alpha-tocopheryl
      succinate, involves generation of reactive oxygen species (ROS). ROS then mediate
      the formation of disufide bridges between cytosolic Bax monomers, resulting in
      the formation of mitochondrial outer membrane channels. ROS also cause oxidation
      of cardiolipin, triggering the release of cytochrome c and its translocation via
      the activated Bax channels. This model may provide a general mechanism for the
      action of inducers of apoptosis and anticancer drugs, mitocans, targeting
      mitochondria via ROS production.

PMID- 16979627
TI  - Topological accessibility shows a distinct asymmetry in the folds of betaalpha
      proteins.
AB  - A novel measure, called "topological accessibility" quantifies how easy it is to
      reconstruct a protein structure using only local contacts when starting at any
      point on the chain. Plotting this measure for all points in the chain gives a
      picture of how accessible the fold is. Simple folds are accessible from all
      positions, others are accessible only from limited positions while the most
      complex folds are not accessible from any position. The distribution of
      topological accessibility along the chain was found to be completely symmetric
      for the all-alpha and all-beta protein classes. However, for the betaalpha class,
      a distinct asymmetry was found (with probability 10(-30) of being due to chance).
      Examination of the proteins contributing to this signal indicated many that have
      an ancient origin. This suggests that the folds of these proteins may have become
      fixed under the influence of amino-terminal folding before the advent of
      chaperone assisted folding.

PMID- 16979628
TI  - Stereoisomeric bio-inversion key to biosynthesis of firefly D-luciferin.
AB  - The chirality of the luciferin substrate is critical to the luciferin-luciferase
      reaction producing bioluminescence. In firefly, the biosynthetic pathway of D
      luciferin is still unclear, although it can be synthesized in vitro from D
      cysteine. Here, we show that the firefly produces both D- and L-luciferin, and
      that the amount of active D-luciferin increases gradually with maturation stage.
      Studies of firefly body extracts indicate the possible conversion of L-cysteine
      via L-luciferin into D-luciferin, suggesting that the biosynthesis is
      enzymatically regulated by stereoisomeric bio-inversion of L-luciferin. We
      conclude that the selection of chirality in living organisms is not as rigid as
      previously thought.

PMID- 16979630
TI  - Protein-based phylogenetic analysis by using hydropathy profile of amino acids.
AB  - So far, various approaches for phylogenetic analysis have been developed. Almost
      all of them put stress on analyzing nucleic acid sequences or protein primary
      structures. In this paper, we take the physicochemical properties of amino acids
      into account and introduce the hydropathy profile of amino acids into
      phylogenetic analysis. We find that this introduction is effectual and our method
      may be used to complement phylogenetic analysis.

PMID- 16979629
TI  - Shedding of procoagulant microparticles from unstimulated platelets by integrin
      mediated destabilization of actin cytoskeleton.
AB  - Platelet activation by potent, Ca(2+)-mobilizing agonists results in shedding of
      microparticles that are active in coagulation. Here we show that platelets under
      storage produce procoagulant microparticles in the absence of agonist.
      Microparticle formation by resting platelets results from alphaIIbbeta3 signaling
      to destabilization of the actin cytoskeleton in the absence of calpain
      activation. Integrin-mediated spreading of platelets over fibrinogen similarly
      results in microparticle formation. After transfusion of stored platelet
      preparations to thrombocytopenic patients, the microparticles contribute to
      coagulant activity in vivo.

PMID- 16979631
TI  - Role of the membrane interface on the conformation of the caveolin scaffolding
      domain: a CD and NMR study.
AB  - Circular dichroism (CD) and NMR spectroscopy were used to study the
      conformational properties of two synthetic peptides, D82-R101 and D82-I109,
      encompassing the caveolin scaffolding domain (D82-R101), in the presence of
      dodecylphosphocholine (DPC) micelles. Our data show that a stable helical
      conformation of the caveolin scaffolding domain in a membrane mimicking system is
      only obtained for the peptide including the L102-I109 hydrophobic stretch, a part
      of the caveolin intra-membrane domain. Through chemical shift variations, an
      ensemble of six residues of the D82-L109 peptide, mainly located in the
      V(94)TKYWFYR(101) motif were found to detect the presence of phosphatidylserine
      solubilized in DPC micelles. Our results constitute a first step for elucidating
      at a residue level the conformational properties of the central region of the
      caveolin-1 protein.

PMID- 16979633
TI  - Transcriptional autoregulation by Mycobacterium tuberculosis PhoP involves
      recognition of novel direct repeat sequences in the regulatory region of the
      promoter.
AB  - The PhoP-PhoR two-component system is essential for virulence and intracellular
      growth of Mycobacterium tuberculosis (MTB) in human and mouse macrophages or in
      mice. Here, PhoP and truncated PhoR sensor proteins were shown to participate in
      phosphotransfer reactions using conserved residues characteristic of two
      component signaling systems. beta-Galactosidase activity originating from phoP
      promoter-lacZ construct was inhibited in presence of PhoP, suggesting
      transcriptional auto-inhibition by the response regulator. In vitro binding of
      PhoP is consistent with the in vivo transcriptional repression, indicating
      phosphorylation-independent assembly of the transcription initiation complex at
      elevated concentrations of PhoP. DNaseI protection studies reveal a consensus
      recognition sequence within the phoP promoter that includes three 9-bp direct
      repeat units. Each repeat unit adjusts to the consensus
      (1)AC(T)/(G)(T)/(G)(T)/(G)P(y)AP(u)C(9). Alteration in the sequence of the newly
      identified direct repeat units relieved phoP transcriptional repression in
      presence of PhoP, suggesting that PhoP represses its own expression by sequence
      specific interaction(s) with the repeat units. Together, these results identify
      so far unknown PhoP-regulated genetic determinants in the regulatory region of
      the phoP promoter that are central to understanding of how PhoP may possibly
      function as a global regulator in MTB.

PMID- 16979632
TI  - Two cysteine protease inhibitors, EhICP1 and 2, localized in distinct
      compartments, negatively regulate secretion in Entamoeba histolytica.
AB  - The enteric protozoan parasite Entamoeba histolytica uniquely possesses two
      isotypes of ICPs, a novel class of inhibitors for cysteine proteases. These two
      EhICPs showed a remarkable difference in the ability to inhibit cysteine protease
      (CP) 5, a well-established virulence determinant, whereas they equally inhibited
      CP1 and CP2. Immunofluorescence imaging and cellular fractionation showed that
      EhICP1 and EhICP2 are localized to distinct compartments. While EhICP1 is
      localized to the soluble cytosolic fraction, EhICP2 is targeted from lysosomes to
      phagosomes upon erythrocyte engulfment. Overexpression of either EhICP1 or EhICP2
      caused reduction of intracellular CP activity, but not the amount of CP, and
      decrease in the secretion of all major CPs, suggesting that both EhICPs are
      involved in the trafficking and/or interference with the major CP activity. These
      data indicate that the two EhICPs, present in distinct subcellular compartments,
      negatively regulate CP secretion, and, thus, the virulence of this parasite.

PMID- 16979634
TI  - Citrus auraptene targets translation of MMP-7 (matrilysin) via ERK1/2-dependent
      and mTOR-independent mechanism.
AB  - Matrix metalloproteinase (MMP)-7 is considered to play essential roles in cancer
      progression. We examined the efficacy of auraptene, a citrus coumarin derivative,
      for suppressing MMP-7 expression in the human colorectal adenocarcinoma cell line
      HT-29. Auraptene remarkably inhibited the production of proMMP-7 protein, without
      affecting its mRNA expression level. Rapamycin, an inhibitor of mammalian target
      of rapamycin (mTOR), showed similar results, suggesting that auraptene suppresses
      mTOR-dependent proMMP-7 translation. Interestingly, however, auraptene showed no
      effects on the activation of Akt/mTOR signaling, whereas the phosphorylation
      levels of 4E binding protein (4EBP)1 and eukaryotic translation initiation factor
      (eIF)4B were substantially decreased. In addition, auraptene remarkably
      dephosphorylated constitutively activated extracellular signal-regulated kinase
      (ERK)1/2. Transfection of ERK1/2 siRNA led to a significant reduction of proMMP-7
      protein production as well as of the phosphorylation of eIF4B. These results
      demonstrate that auraptene targets the translation step for proMMP-7 protein
      synthesis by disrupting ERK1/2-mediated phosphorylation of 4EBP1 and eIF4B.

PMID- 16979635
TI  - Effect of sperm glutathione peroxidases 1 and 4 on embryo asymmetry and
      blastocyst quality in oocyte donation cycles.
AB  - OBJECTIVE: To prospectively determine the impact of concrete components of the
      sperm oxidative glutathione stress system in terms of enzymatic activity and
      mitochondrial RNA (mRNA) expression on embryo quality and reproductive outcome.
      Human spermatozoa use the glutathione system to inactivate reactive oxygen
      metabolites, and there is a close correlation between some components of the
      glutathione system and male fertility. However, very few data are published
      regarding this system in sperm cells and its effect on fertilization ability and
      embryo development in human beings. DESIGN: An oocyte-donation model, used to
      homogenize the female factor. SETTING: University-affiliated private IVF setting.
      PATIENT(S): Semen samples from infertile males (n = 43) of couples undergoing
      oocyte-donation cycles (n = 43). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Gene expression and activity of glutathione peroxidases (GPXs) 1 and 4,
      glutathione reductase, and intracellular glutathione (GSH) by fluorescent
      quantitative polymerase chain reaction and spectrophotometry, respectively.
      RESULT(S): Fertilization rate, pronuclear number, asymmetry, and pronuclear body
      distribution were not correlated with any sperm glutathione parameters that were
      considered. When day 3 embryo parameters were evaluated, only GPX4 mRNA
      expression in sperm cells was statistically significantly lower when asymmetric
      embryos were observed. Also, worst embryo development and morphology on day 5 was
      statistically significantly correlated with lower sperm GPX1 activity (101.07 vs.
      258.8 IU/mg protein). Glutathione system analysis in fresh sperm was not
      statistically significantly different in patients achieving pregnancy compared
      with those who not, and we did not find any correlation with implantation rate.
      CONCLUSION(S): We have been able to correlate embryo morphology on day 3 with the
      sperm expression of GPX family members. The results indicate that sperm-derived
      mRNA may condition human embryo quality and persist even to blastocyst stage. The
      correlation of the sperm GPX family mRNA expression with embryo health appears
      quite promising for discovery of molecular causes of male infertility.

PMID- 16979636
TI  - Mutational screening of FOXO3A and FOXO1A in women with premature ovarian
      failure.
AB  - FOXO3A and FOXO1A are excellent candidate genes for the development of premature
      ovarian failure and have not been analyzed previously in POF patients.
      Potentially causal mutations in FOXO3A (2/90; 2.2%) and FOXO1A (1/90; 1.1%) were
      identified in POF patients; however, the pathological role of these mutations
      will be determined only by screening increased numbers of patients and controls,
      or by functional studies.

PMID- 16979637
TI  - No differences in the DNA methylation pattern in mouse zygotes produced in vivo,
      in vitro, or by intracytoplasmic sperm injection.
AB  - The pattern and degree of pronuclear DNA methylation has been evaluated in
      naturally, in in vitro, or in intracytoplasmic sperm injection (ICSI)-produced
      mouse embryos. The results show no differences between all experimental groups
      and confirm the relative safety of IVF and ICSI.

PMID- 16979638
TI  - Expression of aquaporin 2 in human endometrium.
AB  - OBJECTIVE: To study the expression of aquaporin-2 (AQP2) in human endometrium.
      DESIGN: Prospective clinical study. SETTING: Hospital-based unit for gynecology
      and obstetrics and research laboratories. PATIENT(S): Healthy women with proven
      fertility who were divided into four groups according to LH peak.
      INTERVENTION(S): Endometrial biopsies were obtained from 34 women on cycle days
      LH+4 to LH+14. MAIN OUTCOME MEASURE(S): Localization of AQP2 in human endometrium
      during normal cycle using immunohistochemistry, verification of AQP2 expression
      through detection of AQP2 mRNA in reverse transcriptase-polymerase chain reaction
      (RT-PCR), detection of pinopodes using scanning electron microscopy, and
      confirmation of AQP2 on pinopodes in confocal microscopy. RESULT(S):
      Immunostaining of AQP2 is present in the luminal and glandular epithelium but not
      in the stroma. Some vessels stained positive for AQP2. When present, pinopodes
      stained positive, which was confirmed using confocal microscopy. A significant
      increase in staining intensity was seen in the glandular and luminal epithelium
      during the mid and late luteal phases of the cycle. The presence of AQP2 in human
      endometrium was also confirmed by RT-PCR. CONCLUSION(S): AQP2 is present in the
      human endometrium. The expression of AQP2 appears to be cycle dependent and
      suggests a role for AQP2 in implantation, edema, and/or menstruation.

PMID- 16979639
TI  - Does adrenal responsiveness vary with sex and reproductive status in Egernia
      whitii, a viviparous skink?
AB  - In mammals, oestrogens generally stimulate adrenal function whilst androgens are
      inhibitory, and gestating females down-regulate their acute response to stressors
      in order to protect current reproductive investment. This study aimed to
      determine if adrenocortical function is similarly modulated by sex and
      reproductive status in the viviparous lizard, Egernia whitii. We compared the
      adrenocortical response to acute capture stress in female E. whitii during active
      (post-ovulatory and gestating) and quiescent (post-partum) phases of their
      reproductive cycle. We also compared the responses of reproductively quiescent
      males and females to acute stress and ACTH challenge to determine if there are
      sex-related differences in HPA axis activity when the influence of reproductive
      hormones is minimal. The females' responses to acute capture stress varied
      significantly with reproductive stage, and quiescent females displayed the
      strongest immediate response, with a rapid and sustained increase in plasma
      corticosterone (CORT) concentrations. Post-ovulatory females showed the most
      conservative adrenocortical response and while gestating females showed a large
      immediate response, this was not as prolonged as in quiescent females.
      Reproductively quiescent males and females exhibited similar responses to acute
      stress, and also responded similarly to ACTH injection, with plasma CORT reaching
      maximal concentrations of 52.1 and 59.4 ng/mL, respectively. Reproductively
      quiescent females treated with oestrogen exhibited greater responsiveness to ACTH
      than control females, although basal plasma CORT concentrations were unaltered:
      these results suggest that the attenuation of the acute stress response observed
      in reproductively active females of E. whitii may be regulated upstream of ACTH
      secretion. Our results demonstrate that the activity of the HPA axis is modulated
      by reproductive status in this viviparous reptile, and that gestating females are
      able to buffer their embryos from the potentially adverse effects of elevated
      plasma corticosteroids.

PMID- 16979640
TI  - Perception and education of unilateral weightbearing amongst health care
      professionals.
AB  - Studies have shown that healthy individuals cannot accurately judge the degree of
      weightbearing through one lower extremity [Bohannon R, Waters G, Cooper J.
      Perception of unilateral lower extremity weightbearing during bilateral upright
      stance. Percept Mot Skills 69;1989:875-80]. This study of 40 healthcare
      professionals assessed a simple education process to see if this perception could
      be improved. Weightbearing was assessed before and after the education process, a
      familiarisation exercise with a set of bathroom scales. The education process had
      no significant effect on individual's perception of weightbearing, nor was there
      any difference between members of the multi-disciplinary team. As an important
      aspect of patient care, further work is necessary to identify an accurate and
      reproducible method of quantifying weightbearing.

PMID- 16979641
TI  - District nursing staff and depression: a psychometric evaluation of Depression
      Attitude Questionnaire findings.
AB  - BACKGROUND: Mental health problems such as depression are common in primary care
      settings and patients with chronic medical problems are at an increased risk.
      This co-morbidity suggests that district nursing services are particularly likely
      to encounter psychological problems in their patients. Mental health problems are
      poorly recognised and inadequately treated in primary care. In part this may be
      due to stigmatising views of mental illness, which negatively influence help
      seeking and user experiences. Likewise providers' attitudes are likely to play a
      significant part in the management of such problems. OBJECTIVES: The aims of this
      study were extend knowledge of district nursing staff attitudes to depression and
      explore the psychometric properties of a depression attitude measure used with
      this staff group. DESIGN AND SETTINGS: The Depression Attitude Questionnaire
      (DAQ) was used within a postal questionnaire survey of district nursing services
      in three areas, Jersey (Channel Islands), Lewisham, and Hertfordshire.
      PARTICIPANTS: All staff (community nurses, district nurses and home care staff)
      were contacted; 217 (66%) staff responded to the survey, and 189 (57%) completed
      the DAQ. RESULTS: Three factors were derived from the DAQ accounting for 47% of
      the variance. The factor solution appeared stable and provided meaningful
      dimensions, however the internal consistency of the measure and of its derived
      subscales was low (Cronbach's alpha between 0.59 and 0.64). The factors were
      labelled pessimism about depression and its treatment, tendency to defer to
      specialists, and professional ease in working with depressed patients. Staff
      responses revealed generally optimistic views concerning depression treatment,
      strongly rejecting deterministic attitudes to this condition. CONCLUSIONS: The
      DAQ has been widely employed to measure and compare attitudes of staff from
      various disciplines and specialisms. The current evaluation has provided a more
      detailed examination of its psychometric properties than previously available,
      but low internal consistency levels indicate further examination of this area is
      warranted.

PMID- 16979642
TI  - From multidimensional support to decreasing visibility: a field study on care
      culture in paediatric and adult diabetes outpatient clinics.
AB  - BACKGROUND: As the incidence of Type 1 diabetes mellitus has increased during
      childhood, more patients will experience the transfer from paediatric diabetes
      care to adult diabetes care. In order to achieve a coherent care system it is
      essential to identify conditions, events and actions that hinder and facilitate a
      successful transition between these settings. OBJECTIVES: The aim of this study
      was to describe care culture in paediatric and adult diabetes outpatient clinics
      and implications for care of adolescents in those settings. METHODS: Fifty-one
      participant observations and 10 semi-structured interviews with diabetes care
      providers were carried out in two paediatric clinics and two adult clinics in
      Sweden. Data were analysed simultaneously with data collection, using a constant
      comparative method developed in the grounded theory tradition. RESULTS: In the
      analysis process, one core category, four categories and subcategories were
      generated. The core category shifting aspects of diabetes care culture is related
      to the categories. The categories support of self-management and unfocused
      behaviour describes mostly similar strategies and attitudes in paediatric and
      adult diabetes care, while multidimensional support and decreasing visibility
      describes differences in characteristics of care culture in paediatric versus
      adult diabetes care. CONCLUSIONS: The decreased visibility might have
      consequences for vulnerable patients, such as those with insufficient metabolic
      control and self-management abilities. By illuminating shifting aspects of care
      culture, care providers can be given a basis for reflection and discussion of how
      the care is provided in their own setting and how different environmental
      conditions and care strategies can promote formal and informal contacts between
      patients and care providers.

PMID- 16979643
TI  - Preferential invasion of reticulocytes during late-stage Plasmodium berghei
      infection accounts for reduced circulating reticulocyte levels.
AB  - Insufficient circulating reticulocytes have been observed during severe malarial
      anaemia in both human and murine infection, and are often attributed to reduced
      production of red cell precursors. However, a number of Plasmodium species
      display a preference for invading reticulocytes rather than erythrocytes. Thus,
      the reduction in circulating reticulocyte numbers may arise as a result both of
      increased parasitization and lysis of reticulocytes, as well as decreased
      production. We have analysed both circulating reticulocyte numbers and the
      percentage of infected reticulocytes during murine Plasmodium berghei infection.
      We found a large reduction in circulating numbers when compared with an
      equivalent chemically induced anaemia. However, mathematical analysis of parasite
      and red cell numbers revealed the preference of P. berghei for reticulocytes to
      be approximately 150-fold over that for erythrocytes, leading to increased
      destruction of reticulocytes. Although erythropoietic suppression is evident
      during the first week of P. berghei infection, this preferential infection and
      destruction of reticulocytes is sufficient to mediate ongoing reduced levels of
      circulating reticulocytes during the latter stages of infection, following
      compensatory erythropoiesis in response to haemolytic anaemia.

PMID- 16979644
TI  - High infection rates at low transmission potentials in West African
      onchocerciasis.
AB  - Onchocerciasis has been successfully controlled for many years in endemic
      countries but more than 120 million people are still at risk. Factors which
      stabilise the persistence of the parasite in the population must be studied to
      minimise the future risk of re-infection. Among these factors, the relationship
      between the annual transmission potential and the parasite establishment rate is
      a main determinant which has to date not been quantified. Using entomological
      information and palpation data collected by the Onchocerciasis Control Programme
      in West Africa prior to the initiation of control activities, we derive annual
      transmission potential-dependent estimates of the parasite establishment rate
      from statistical analyses and computer simulations. Even at very low transmission
      intensities, the filarial parasite Onchocerca volvulus can efficiently establish
      in the human population, originating from an infection process which is strongly
      limited with respect to the annual transmission potential. Implementing the
      estimates into a simplified transmission model predicts that the critical annual
      biting rate, below which transmission is not possible, is much lower than
      previously assumed. We conclude that under the current strategy of mass
      distribution of microfilaricides without additional measures of vector control,
      the risk of re-infection is higher than previously assumed.

PMID- 16979645
TI  - Occupational, commuting and leisure-time physical activity in relation to
      coronary heart disease among middle-aged Finnish men and women.
AB  - OBJECTIVE: To examine the association of different levels of occupational,
      commuting, and leisure-time physical activity with the risk of coronary heart
      disease (CHD) events. METHODS AND RESULTS: The study comprised 47,840 Finnish
      participants aged 25-64 years without history of CHD and stroke at baseline.
      During a mean follow-up of 18.9 years, 4660 new CHD events were documented. The
      multivariable-adjusted (age, body mass index, systolic blood pressure, total
      cholesterol, education, alcohol consumption, smoking, history of diabetes, and
      other two types of physical activity) hazard ratios (HRs) of CHD events
      associated with low, moderate, and high occupational activity were 1.00, 0.87,
      and 0.90 (P(trend)=0.019) for men, and 1.00, 0.75, and 0.80 (P(trend)<0.001) for
      women, respectively. The multivariable-adjusted HRs of CHD events associated with
      low, moderate, and high leisure-time physical activity were 1.00, 0.95, and 0.84
      (P(trend)=0.026) for men, and 1.00, 0.85, and 0.77 (P(trend)=0.003) for women,
      respectively. Active commuting had a significant inverse association with the
      risk of CHD events in women but not in men. CONCLUSION: Moderate or high levels
      of occupational or leisure-time physical activity are associated with a reduced
      risk of CHD. Daily walking or cycling to and from work is associated with a
      decreased risk of CHD among women.

PMID- 16979646
TI  - Fenofibrate improves age-related endothelial dysfunction in rat resistance
      arteries.
AB  - This study was designed to test the hypothesis that fenofibrate, the peroxisome
      proliferator-activated receptor alpha (PPARalpha) activator, improves age-related
      endothelial dysfunction in small mesenteric arteries (SMA). Adult and aged rats
      were treated with fenofibrate and then endothelium-dependent relaxations of SMA;
      expressions of endothelial NO synthase (eNOS), cyclo-oxygenase (COX-1 and COX-2)
      and superoxide dismutases (SOD) (Cu/Zn SOD, Mn SOD and EC SOD) proteins and
      release of TXB(2) and 6-keto-PGF(1alpha) were assessed. Fenofibrate improved
      endothelium-dependent vasodilatation of arteries from old rats and decreased
      participation of endothelial vasoconstrictor products, sensitive to COX-1 and COX
      2 inhibitors and acting on Tp receptor. Fenofibrate decreased expressions of COX
      1 and COX-2, and generation of TXA(2). Release of vasodilator PGI(2) and U46619
      induced contraction remained unaltered. Neither NO-mediated vasodilatation nor
      eNOS expression was affected. The addition of the scavengers, SOD and catalase
      increased relaxation only in SMA from control rats. Finally, fenofibrate did not
      change expressions of Cu/Zn SOD and Mn SOD but it increased EC SOD towards that
      observed in arteries from adult rats. Fenofibrate improves endothelial function
      in resistance arteries from aged rats by decreasing expression of COX-1 and COX-2
      together with enhancing anti-oxidant capacity of the vessel wall probably through
      the increased expression of EC SOD. This study provides evidence that PPARalpha
      may have clinical applications toward maintaining endothelial function during
      ageing.

PMID- 16979647
TI  - Selective gene silencing of either MMP-2 or MMP-9 inhibits invasion of human
      saphenous vein smooth muscle cells.
AB  - Activation of matrix metalloproteinases (MMPs) facilitates smooth muscle cell
      (SMC) invasion, an important event in the development of intimal hyperplasia in
      saphenous vein (SV) bypass grafts. In this study, we performed selective gene
      silencing using small inhibitory RNA (siRNA) oligonucleotides to examine the
      relative contributions of MMP-2 and MMP-9 to the invasiveness of cultured human
      SV-SMCs. Cultures were established from human SV obtained from patients
      undergoing coronary artery bypass surgery. Transfection of SV-SMCs with MMP-2
      siRNA selectively reduced MMP-2 secretion and inhibited invasion through a
      Matrigel barrier. Supplementation of medium with recombinant MMP-2 overcame these
      effects. Similarly, transfection of SV-SMCs with MMP-9 siRNA selectively reduced
      MMP-9 secretion and subsequent invasion, effects reversed by recombinant MMP-9
      supplementation. Neither MMP-2 nor MMP-9 siRNA inhibited SV-SMC migration in the
      absence of a Matrigel barrier. Our data demonstrate that selective gene-silencing
      of either MMP-2 or MMP-9 markedly reduces the invasive capacity of cultured human
      SV-SMCs, indicating that these MMPs play distinct non-overlapping roles in SV-SMC
      invasion in vitro. Specific manipulation of either MMP-2 or MMP-9 may therefore
      provide a valuable strategy for prevention of SV graft stenosis in man.

PMID- 16979648
TI  - Electrophoretic motion of a spherical particle in a converging-diverging
      nanotube.
AB  - A charged spherical particle is concentrically positioned in a converging
      diverging nanotube filled with an electrolyte solution, resulting in an electric
      double layer (EDL) forming around the particle's surface. In the presence of an
      axially applied electric field, the particle electrophoretically migrates along
      the axis of the nanotube due to the electrostatic and hydrodynamic forces acting
      on the particle. In contrast to a cylindrical nanotube with a constant cross
      sectional area in which the electric field is almost uniform, the presence of a
      converging-diverging section in a nanotube alters the electric field, perturbs
      the charge distribution, and induces a pressure gradient and a recirculating flow
      that affect the electrostatic and hydrodynamic forces acting on both the particle
      and the fluid. Depending on the magnitude of the surface charge density along the
      nanotube's wall, the particle's electrophoretic motion may be significantly
      accelerated as the particle transverses the converging-diverging section. A
      continuum model consisting of the Nernst-Planck, Poisson, and Navier-Stokes
      equations for the ionic concentrations, electric potential, and flow field is
      implemented to compute the particle's velocity as a function of the particle's
      size, the nanotube's geometry, surface charges, electric field intensity, bulk
      electrolyte concentration, and the particle's location. When the particle is
      negatively charged and the wall of the nanotube is uncharged, the particle
      migrates in the direction opposite to that of the applied electric field and the
      presence of the converging-diverging section significantly accelerates the
      particle's motion. This, however, is not always true when the nanotube's wall is
      charged with the same sign as that of the particle. Once the ratio of the surface
      charge density of the nanotube's wall to that of the particle exceeds a certain
      value, the negatively charged particle will not translocate through the tube
      toward the anode and does not attain the maximum velocity at the throat of the
      converging-diverging section. One can envision such a device to be a nanofilter
      that allows molecules with surface charge densities much higher than that of the
      wall to go through the nanofilter, while preventing molecules with surface charge
      densities lower than that of the wall from passing through the nanofilter. The
      induced recirculating flow may be used to enhance mixing and to stretch, fold,
      and trap molecules in nanofluidic detectors and reactors.

PMID- 16979649
TI  - Optical factors determined by the T-matrix method in turbidity measurement of
      absolute coagulation rate constants.
AB  - Turbidity measurement for the absolute coagulation rate constants of suspensions
      has been extensively adopted because of its simplicity and easy implementation. A
      key factor in deriving the rate constant from experimental data is how to
      theoretically evaluate the so-called optical factor involved in calculating the
      extinction cross section of doublets formed during aggregation. In a previous
      paper, we have shown that compared with other theoretical approaches, the T
      matrix method provides a robust solution to this problem and is effective in
      extending the applicability range of the turbidity methodology, as well as
      increasing measurement accuracy. This paper will provide a more comprehensive
      discussion of the physical insight for using the T-matrix method in turbidity
      measurement and associated technical details. In particular, the importance of
      ensuring the correct value for the refractive indices for colloidal particles and
      the surrounding medium used in the calculation is addressed, because the indices
      generally vary with the wavelength of the incident light. The comparison of
      calculated results with experiments shows that the T-matrix method can correctly
      calculate optical factors even for large particles, whereas other existing
      theories cannot. In addition, the data of the optical factor calculated by the T
      matrix method for a range of particle radii and incident light wavelengths are
      listed.

PMID- 16979650
TI  - Polar fluid model of viscoelastic membranes and interfaces.
AB  - The polar surface fluid model is used to derive the generalized dynamic shape
      equation and the interfacial rheological material functions for viscoelastic
      membranes and curved interfaces, taking viscous bending and torsion modes into
      full account. The materials modeling approach based on the polar surface fluid
      leads to the integration of bending and torsion dissipative modes with their
      elastic counterparts that appear in the dynamic shape equation and in the
      interfacial rheological functions. The covariant bending and torsion rates
      derived in this paper are shown to be related to the interfacial co-rotational
      derivative of the curvature tensor. The dynamic shape equation is used to analyze
      shape fluctuation in planar geometries, and to establish the role of bending
      dissipation in shape dynamics. The dynamic shape equation generalizes the static
      Helfrich shape equation by incorporating bending and torsion dissipation, and it
      generalizes the dynamic shape equation based on the Boussinesq-Scriven model by
      incorporating bending and torsion elasticity and dissipation.

PMID- 16979651
TI  - Integral equation for calculation of distribution function of activation energy
      of shear viscosity.
AB  - A new technique of calculation of a distribution function of activation energy
      (f(E)) of shear viscosity based on a regularization procedure applied to the
      Fredholm integral equation of the first kind has been developed using the Baxter
      Drayton and Brady model for concentrated and flocculated suspensions. This
      technique has been applied to the rheological data obtained at different shear
      rates for aqueous suspensions with fumed silica A-300 and low-molecular (3,4,5
      trihydroxybenzoic acid and 1,5-dioxynaphthalene) or high-molecular (poly(vinyl
      pyrrolidone) of 12.7 kDa and ossein of 20-29 kDa) compounds over a wide
      concentration range (up to 25 wt% of both components) and at different
      temperatures. Monomodal f(E) distributions are observed for the suspensions with
      individual A-300 or A-300 with a low amount of adsorbed organics. In the case of
      larger amounts of nanosilica and organics the f(E) distributions are multimodal
      because of stronger structurization and coagulation of the systems that require a
      high energy to break the coagulation structures resisting to the shear flow.

PMID- 16979652
TI  - A true summer diapause induced by high temperatures in the cotton bollworm,
      Helicoverpa armigera (Lepidoptera: Noctuidae).
AB  - Summer diapause in the cotton bollworm, Helicoverpa armigera (Hubner), which
      prolongs the pupal stage, particularly in males, is induced by high temperatures.
      In the laboratory, summer-diapausing pupae of H. armigera were induced at high
      temperatures (33-39 degrees C) with a photoperiod of LD8:16; winter-diapausing
      and non-diapausing pupae, cultured at 20 degrees C with a photoperiod of LD8:16
      and at 27 degrees C, LD16:8, respectively, acted as a control. Retention time of
      eye spots, weight, and lipid and glycogen levels were compared. At high
      temperatures, both body weight and energy storage capacity were much higher in
      summer-diapausing pupae than in non-diapausing pupae reared at 33-39 degrees C.
      At temperatures (>33 degrees C) high enough to maintain summer diapause, the eye
      spots of summer-diapausing pupae did not move during the 30-day experiment.
      However, eye spots of summer-diapausing pupae placed at 30 degrees C began to
      move about 10 days after they were transferred, significantly later than in non
      diapausing pupae reared at 33-39 degrees C or non-diapausing pupae reared at 27
      degrees C, which initiated eye spot movement 2 days after pupation. The
      differences in retention time of eye spots between summer- and winter-diapausing
      pupae shows that winter diapause is more intense than summer diapause in this
      insect. The weight loss, and lipid and glycogen metabolism curves indicate that
      the summer-diapausing pupae's metabolism is very low. We conclude that summer
      diapause in the cotton bollworm is a true diapause and that the summer diapause
      enables the cotton bollworm to withstand the high temperatures of summer.

PMID- 16979653
TI  - Major components in the hairpencil secretion of a butterfly, Euploea mulciber
      (Lepidoptera, Danaidae): their origins and male behavioral responses to
      pyrrolizidine alkaloids.
AB  - Two compounds, 9,10-epoxytetrahydroedulan (ET) and viridiflorine beta-lactone
      (VL), were identified as major components from the hairpencils of field-caught
      males of a danaid butterfly, Euploea mulciber. By contrast, laboratory-reared
      males entirely lacked VL, but possessed a significant quantity of ET. Various
      feeding experiments with larvae and indoor adult males strongly suggested that ET
      is biosynthesized de novo only after eclosion from nutrients ingested during the
      larval development. Since VL was suspected to be derived from pyrrolizidine
      alkaloids (PAs) acquired as an adult, tests for feeding response to and oral
      administration of four PAs (a 4:1 mixture of intermedine/lycopsamine, heliotrine,
      monocrotaline, and retronecine) were conducted. When the tarsi or proboscis were
      stimulated with PA solutions, males showed positive feeding responses (proboscis
      extension and sucking movements) to intermedine/lycopsamine, heliotrine, and
      retronecine in decreasing order of responsiveness, thereby providing evidence
      that male adults are endowed with taste receptor(s) specific to PAs on the legs
      as well as on the proboscis. Differently from gustatory responsiveness, only
      males fed with intermedine/lycopsamine produced a significant quantity of VL (ca.
      35 microg/male), whereas those that ingested heliotrine or monocrotaline
      hydrochloride produced traces of VL (<0.18 microg/male). Uptake of retronecine
      did not lead to VL formation at all. In behavioral bioassays to test the
      attractivity of PAs to males, all individuals tested were attracted exclusively
      to intermedine/lycopsamine. This shows that certain PA(s) per se serve as
      attractant(s) for males in locating PA sources, and further suggests that in the
      field, males will seek particular PA(s) that are indispensable as precursors for
      the efficient biosynthesis of VL.

PMID- 16979654
TI  - Suppression of HIV-1 protease inhibitor resistance by phosphonate-mediated
      solvent anchoring.
AB  - The introduction of human immunodeficiency virus type 1 (HIV-1) protease
      inhibitors (PIs) markedly improved the clinical outcome and control of HIV-1
      infection. However, cross-resistance among PIs due to a wide spectrum of
      mutations in viral protease is a major factor limiting their broader clinical
      use. Here we report on the suppression of PI resistance using a covalent
      attachment of a phosphonic acid motif to a peptidomimetic inhibitor scaffold. The
      resulting phosphonate analogs maintain high binding affinity to HIV-1 protease,
      potent antiretroviral activity, and unlike the parent molecules, display no loss
      of potency against a panel of clinically important PI-resistant HIV-1 strains. As
      shown by crystallographic analysis, the phosphonate moiety is highly exposed to
      solvent with no discernable interactions with any of the enzyme active site or
      surface residues. We term this effect "solvent anchoring" and demonstrate that it
      is driven by a favorable change in the inhibitor binding entropy upon the
      interaction with mutant enzymes. This type of thermodynamic behavior, which was
      not found with the parent scaffold fully buried in the enzyme active site, is a
      result of the increased degeneracy of inhibitor binding states, allowing
      effective molecular adaptation to the expanded cavity volume of mutant proteases.
      This strategy, which is applicable to various PI scaffolds, should facilitate the
      design of novel PIs and potentially other antiviral therapeutics.

PMID- 16979655
TI  - Kinetic folding and assembly mechanisms differ for two homologous heptamers.
AB  - Here we investigate the time-resolved folding and assembly mechanism of the
      heptameric co-chaperonin protein 10 (cpn10) in vitro. The structure of cpn10 is
      conserved throughout nature: seven beta-barrel subunits are non-covalently
      assembled through beta-strand pairings in an overall doughnut-like shape. Kinetic
      folding/assembly experiments of chemically denatured cpn10 from Homo sapiens
      (hmcpn10) and Aquifex aeolicus (Aacpn10) were monitored by far-UV circular
      dichroism and fluorescence. We find the processes to be complex, involving
      several kinetic steps, and to differ between the mesophilic and hyper
      thermophilic proteins. The hmcpn10 molecules partition into two parallel
      pathways, one involving polypeptide folding before protein-protein assembly and
      another in which inter-protein interactions take place prior to folding. In
      contrast, the Aacpn10 molecules follow a single sequential path that includes
      initial monomer misfolding, relaxation to productive intermediates and,
      subsequently, final folding and heptamer assembly. An A. aeolicus variant lacking
      the unique C-terminal extension of Aacpn10 displays the same kinetic mechanism as
      Aacpn10, signifying that the tail is not responsible for the rapid misfolding
      step. This study demonstrates that molecular details can overrule similarity of
      native-state topology in defining apparent protein-biophysical properties.

PMID- 16979656
TI  - The structure of Apo-wild-type cellular retinoic acid binding protein II at 1.4 A
      and its relationship to ligand binding and nuclear translocation.
AB  - CRABPII is a small, cytosolic protein that solubilizes and transfers retinoic
      acid (RA) to the nucleus while also enhancing its transcriptional activity. We
      have determined the first high-resolution structure of apo-wild type (WT) CRABPII
      at 1.35 A. Using three different data sets collected on apo-WT CRABPII we have
      shown that apo- and holo-CRABPII share very similar structures. Binding of RA
      appears to increase the overall rigidity of the structure, although the induced
      structural changes are not as pronounced as previously thought. The enhanced
      structural rigidity may be an important determinant for the enhanced nuclear
      localization of the RA-bound protein. Comparison of our apo-WT with a mutant apo
      CRABPII structure shows that mutation of Arg111, a conserved residue of CRABPII
      and a key residue in RA binding, causes structural changes in the molecule. We
      further investigated the structural importance of conserved residues by
      determining the structure of the F15W mutant CRABPII (F15W-CRABPII). Our
      structures also demonstrate structural changes induced by crystal packing and
      show that a crystal can harbor demonstrative structural differences in the
      asymmetric unit.

PMID- 16979658
TI  - Mapping of interaction domains mediating binding between BACE1 and RTN/Nogo
      proteins.
AB  - BACE1 is a membrane-bound aspartyl protease that specifically cleaves amyloid
      precursor protein (APP) at the beta-secretase site. Membrane bound reticulon
      (RTN) family proteins interact with BACE1 and negatively modulate BACE1 activity
      through preventing access of BACE1 to its cellular APP substrate. Here, we
      focused our study on RTN3 and further show that a C-terminal QID triplet
      conserved among mammalian RTN members is required for the binding of RTN to
      BACE1. Although RTN3 can form homo- or heterodimers in cells, BACE1 mainly binds
      to the RTN monomer and disruption of the QID triplet does not interfere with the
      dimerization. Correspondingly, the C-terminal region of BACE1 is required for the
      binding of BACE1 to RTNs. Furthermore, we show that the negative modulation of
      BACE1 by RTN3 relies on the binding of RTN3 to BACE1. The knowledge from this
      study may potentially guide discovery of small molecules that can mimic the
      effect of RTN3 on the inhibition of BACE1 activity.

PMID- 16979657
TI  - Activation of ubiquitin ligase SCF(Skp2) by Cks1: insights from hydrogen exchange
      mass spectrometry.
AB  - Skp2 is the substrate recognition subunit of the multi-subunit ubiquitin ligase
      SCF(Skp2). It consists of an N-terminal F-box domain that binds to the Skp1
      subunit and thereby tethers it to the SCF catalytic core, and an elongated C
      terminal domain comprising ten Leucine-rich repeats (LRR) that binds the
      substrate. A small accessory protein, Cks1, is required for SCF(Skp2) to target
      certain substrates, including the Cyclin-dependent kinase inhibitor p27. Here we
      have used hydrogen/deuterium exchange monitored by mass spectrometry to
      investigate the mode of action of Cks1 on SCF(Skp2). We show that complex
      formation between Cks1 and Skp2 causes conformational changes in both proteins in
      regions distant from the respective binding sites. We find that Skp2 interacts
      with a localised region of Cks1 but the interaction causes a global change in the
      hydrogen exchange behaviour of Cks1. Also, whilst Cks1 binds to the most C
      terminal LRRs of the elongated Skp2 molecule, the interaction induces
      conformational changes at the distant N-terminal LRRs, close to the F-box motif.
      Further, binding of Cks1 to Skp2 significantly stabilises the interaction between
      Skp2 and Skp1. The results reveal that the C-terminal substrate recognition
      region of Skp2 is coupled to the N-terminal Skp1-binding region and thereby to
      the SCF catalytic core; this result adds to the model proposed previously that,
      whilst the principal function of the F-box protein is to recruit the substrate,
      an additional function may be to help position the substrate in an optimal way
      within the SCF complex to enable efficient ubiquitin transfer.

PMID- 16979659
TI  - Visualizing the assembly of human Rad51 filaments on double-stranded DNA.
AB  - Rad51 is the core component of the eukaryotic homologous recombination machinery
      and assembles into extended nucleoprotein filaments on DNA. To study the dynamic
      behavior of Rad51 we have developed a single-molecule assay that relies on a
      combination of hydrodynamic force and microscale diffusion barriers to align
      individual DNA molecules on the surface of a microfluidic sample chamber that is
      coated with a lipid bilayer. When visualized with total internal reflection
      fluorescence microscopy (TIRFM), these "molecular curtains" allow for the direct
      visualization of hundreds of individual DNA molecules. Using this approach, we
      have analyzed the binding of human Rad51 to single molecules of double-stranded
      DNA under a variety of different reaction conditions by monitoring the extension
      of the fluorescently labeled DNA, which coincides with assembly of the
      nucleoprotein filament. We have also generated several mutants in conserved
      regions of Rad51 implicated in DNA binding, and tested them for their ability to
      assemble into extended filaments. We show that proteins with mutations within the
      DNA-binding surface located on the N-terminal domain still retain the ability to
      form extended nucleoprotein filaments. Mutations in the L1 loop, which projects
      towards the central axis of the filament, completely abolish assembly of extended
      filaments. In contrast, most mutations within or near the L2 DNA-binding loop,
      which is also located near the central axis of the filament, do not affect the
      ability of the protein to assemble into extended filaments on double-stranded
      (ds)DNA. Taken together, these results demonstrate that the L1-loop plays a
      crucial role in the assembly of extended nucleoprotein filaments on dsDNA, but
      the N-terminal domain and the L2 DNA-binding loop have significantly less impact
      on this process. The results presented here also provide an important initial
      framework for beginning to study the biochemical behaviors of Rad51 nucleoprotein
      filaments using our novel experimental system.

PMID- 16979661
TI  - X-ray interference studies of crossbridge action in muscle contraction: evidence
      from muscles during steady shortening.
AB  - During normal muscle shortening, the myosin heads must undergo many cycles of
      interaction with the actin filaments sliding past them. It is important to
      determine what range of configurations is found under these circumstances, and,
      in terms of the tilting lever arm model, what range of orientations the lever
      arms undergo. We have studied this using the X-ray interference technique
      described in the previous article, focusing mainly on the changes in the first
      order meridional reflection (M3) as compared to isometric. The change in ratio of
      the heights of the interference peaks indicates how far the mean lever arm angle
      has moved towards the end of the working stroke; the total intensity change
      depends on the angle change, on the number of heads now attached at any one time,
      and on the dispersion of lever arm angles. The latter provides a measure of the
      distance over which myosin heads remain attached to actin as they go through
      their working strokes. Surprisingly, the mean position of the attached heads
      moves only about 1 nm inwards (towards the center of the A-band) at low velocity
      shortening (around 0.9 T0): their dispersion changes very little. This shows that
      they must be detaching very early in the working stroke. However, at loads around
      0.5 T0, the mean lever arm angle is about half way towards the end of the working
      stroke, and the dispersion of lever arm angles (with a uniform dispersion) is
      such as to distribute the heads throughout the whole of the working stroke. At
      higher velocities of shortening (at 0.3 T0), the mean position shifts further
      towards the end of the stroke, and the dispersion increases further. The details
      of the measurements, together with other data on muscle indicate that the force
      generating mechanism within the myosin heads must have some unexpected
      properties.

PMID- 16979660
TI  - Structural basis of interaction between urokinase-type plasminogen activator and
      its receptor.
AB  - Recent studies indicate that binding of the urokinase-type plasminogen activator
      (uPA) to its high-affinity receptor (uPAR) orchestrates uPAR interactions with
      other cellular components that play a pivotal role in diverse (patho
      )physiological processes, including wound healing, angiogenesis, inflammation,
      and cancer metastasis. However, notwithstanding the wealth of biochemical data
      available describing the activities of uPAR, little is known about the exact mode
      of uPAR/uPA interactions or the presumed conformational changes that accompany
      uPA/uPAR engagement. Here, we report the crystal structure of soluble urokinase
      plasminogen activator receptor (suPAR), which contains the three domains of the
      wild-type receptor but lacks the cell-surface anchoring sequence, in complex with
      the amino-terminal fragment of urokinase-type plasminogen activator (ATF), at the
      resolution of 2.8 A. We report the 1.9 A crystal structure of free ATF. Our
      results provide a structural basis, represented by conformational changes induced
      in uPAR, for several published biochemical observations describing the nature of
      uPAR/uPA interactions and provide insight into mechanisms that may be responsible
      for the cellular responses induced by uPA binding.

PMID- 16979662
TI  - Transfection of the DNA for the receptor KDR/flk-1 attenuates neointimal
      proliferation and luminal narrowing in a coronary stent angioplasty model.
AB  - BACKGROUND: Neointimal proliferation resulting in luminal renarrowing is the
      major cause of restenosis limiting the long-term success of coronary angioplasty
      in 20 to 30% of patients. Local transfection of the DNA encoding for VEGF has
      been shown to enhance re-endothelialization and reduce neointimal proliferation
      in an experimental model. We tested the hypothesis that transfection of the DNA
      for the receptor of vascular endothelial growth factor VEGF, KDR-flk-1, reduces
      neointimal proliferation after angioplasty. METHODS: In a minipig model, we
      performed coronary stent implantation, followed by injection of either KDR/flk-1
      DNA (200 microg of linearized DNA in a CMV-promotor) or LacZ control in two
      coronary artery segments per animal in a randomized, blinded protocol (n = 22
      animals). Expression of KDR/flk-1 was analyzed using in situ hybridization after
      4, 7, and 14 days. RESULTS: In KDR-transfected coronary segments, expression of
      KDR/flk-1 occurred earlier and to much stronger extent compared to LacZ
      transfected segments. After 4 weeks (n = 10) neointimal proliferation and luminal
      narrowing was significantly reduced in KDR/flk-1 transfected animals. No
      expression of locally transfected DNA was detected in other organs. CONCLUSION:
      The hypothesis is supported, that expression of the VEGF-receptor KDR/flk-1 can
      be rate-limiting for endothelial regeneration and that its transient
      overexpression at the time angioplasty can prevent excessive neointimal
      proliferation resulting in restenosis.

PMID- 16979663
TI  - Contractile function of the mechanically lengthened intestine.
AB  - BACKGROUND: The application of longitudinal mechanical force induces lengthening
      of the small intestine. The purpose of this study is to evaluate the contractile
      function of the mechanically lengthened jejunum in a rodent model. MATERIALS AND
      METHODS: Three groups of rats including normal jejunum, isolated jejunal segment
      without mechanical lengthening, and isolated lengthened jejunal segment, were
      studied for contractile function. The isometric contractions of jejunal segments
      were investigated in organ baths for spontaneous activity and response to
      potassium chloride and cholinergic carbachol. RESULTS: The normal control group
      showed a basal spontaneous activity with an average frequency of 33 +/- 0.68
      contractions per min (cpm). The basal spontaneous activity for the isolated group
      had an average frequency of 26 +/- 2.7 cpm and for the lengthened group had an
      average frequency of 24 +/- 5.7 cpm. Although the normal control group had a
      higher frequency of basal spontaneous activity as compared to either the isolated
      or lengthened groups, there was no statistically significant difference between
      the frequencies in the isolated and the lengthened groups. All three groups
      demonstrated a sustained increase in tension upon administration of either
      potassium chloride or carbachol. CONCLUSIONS: The response to pharmacological
      stimulation, as measured by total area under the tension curve and maximal change
      in basal tone, was larger in the normal group than in the isolated groups. The
      addition of longitudinal mechanical force to lengthen the isolated jejunal
      segment did not further alter this change.

PMID- 16979664
TI  - HSP70 enhances macrophage phagocytosis by interaction with lipid raft-associated
      TLR-7 and upregulating p38 MAPK and PI3K pathways.
AB  - BACKGROUND: Exogenous Heat Shock Protein-70 (HSP70), a product of necrotic cell
      death, binds the lipid raft microdomains of macrophages and, within minutes,
      stimulates the phagocytosis and presentation of internalized antigens. The aim of
      this study was to identify (a) the receptor on the lipid raft microdomain that
      interacts with HSP70 and (b) the subsequent signaling pathways that mediate HSP70
      enhanced phagocytosis. METHODS: Cells including RAW264.7, bone-marrow-derived
      macrophages from TLR7-/- mice or controls and cells subjected to genetic methods
      reducing the mRNA expression of TLR7 were used to examine the interaction of
      HSP70 with TLR7. The effect of HSP70-TLR7 interaction on phagocytosis was
      assessed using phagocytosis assays described earlier. RESULTS: HSP70 binds Toll
      like receptor-7 (TLR7) on the lipid raft microdomain of macrophage plasma
      membrane. Subsequent signaling is mediated through phosphoinositide 3-kinase
      (PI3K) and the up-regulation of the p38 MAP kinase pathways, both known
      activators of the phagocytic mechanisms. Reduced expression of TLR7 either via
      short interfering RNA for TLR7 (siRNA-TLR7) or using bone-marrow derived
      macrophages from TLR7-/- mice show that, as macrophages lose expression of TLR7,
      their ability to mediate HSP70-induced phagocytosis undergoes a corresponding
      diminution. Similarly, disruption of lipid rafts or blocking HSP70-TLR7
      interaction or treatment with wortmannin and SB203580, inhibitors of PI3K or p38
      MAPK, respectively, abrogates HSP70-induced macrophage phagocytosis. CONCLUSIONS:
      The interaction of HSP70 and LR-associated TLR7, two phylogenetically conserved
      molecules, activates a rapid, membrane-bound signaling pathway that enhances
      phagocytosis, a vital innate defense mechanism. This study elucidates critical
      mechanistic elements that mediate HSP70-enhanced phagocytosis by macrophages.

PMID- 16979665
TI  - Stochastic payoff evaluation increases the temperature of selection.
AB  - We study stochastic evolutionary game dynamics in populations of finite size.
      Moreover, each individual has a randomly distributed number of interactions with
      other individuals. Therefore, the payoff of two individuals using the same
      strategy can be different. The resulting "payoff stochasticity" reduces the
      intensity of selection and therefore increases the temperature of selection. A
      simple mean-field approximation is derived that captures the average effect of
      the payoff stochasticity. Correction terms to the mean-field theory are computed
      and discussed.

PMID- 16979666
TI  - Whole-body hyperthermia induces up-regulation of vascular endothelial growth
      factor accompanied by neovascularization in cardiac tissue.
AB  - Whole-body hyperthermia (WBH) promotes cardiac protection against
      ischemia/reperfusion injury, in part by up-regulation of heat shock proteins
      (HSP). Whether heat stress also promotes up-regulation of angiogenic factors or
      induces endothelial cell proliferation is unknown. We studied the effects of heat
      stress on up-regulation of vascular endothelial growth factor (VEGF) and growth
      of new blood vessels following WBH. Anesthetized rats were subjected to WBH at 42
      degrees C for 15 min. The control (n=23) and heated (n=55) groups were allowed to
      recover for 4, 12, 24, 48, or 72 h prior to harvesting the heart for Western Blot
      and immunohistochemical assessment of VEGF, HSP70, and platelet endothelial cell
      adhesion molecular-1 (PECAM-1). A significant increase in VEGF and HSP70
      expression was observed as early as 4 h post-heating. The Western Blot analysis
      revealed a close temporal correlation between up-regulation of HSP70 and VEGF.
      Maximum VEGF and HSP70 expression occurred at 12 and 24 h post-heating in the
      left and right ventricles, respectively. The right ventricle showed the greatest
      expression of both VEGF and HSP70. Immunostaining revealed that VEGF was focally
      increased in the endothelial cells of capillaries, small arteries, and in
      interstitium. At 48 and 72 h post-heating, multiple areas of extensive capillary
      proliferation occurred in the epicardial region of the right ventricle. These
      observations were verified by quantitative analysis of the density of blood
      vessels as determined by PECAM-1 staining. Our experiments show that sublethal
      heat stress can lead to upregulation of both VEGF and HSP70 in cardiac tissue and
      promote focal endothelial proliferation in the heart.

PMID- 16979667
TI  - The use of time-series data in the assessment of macrobenthic community change
      after the cessation of sewage-sludge disposal in Liverpool Bay (UK).
AB  - Sewage sludge was disposed of in Liverpool Bay for over 100 years. Annual amounts
      increased from 0.5 million tonnes per annum in 1900 to approximately 2 million
      tonnes per annum by 1995. Macrofauna and a suite of environmental variables were
      collected at a station adjacent to, and a reference station distant from, the
      disposal site over 13 years, spanning a pre- (1990-1998) and post- (1999-2003)
      cessation period. Univariate and multivariate analyses of the time-series data
      showed significant community differences between reference and disposal site
      stations and multivariate analyses revealed station-specific community
      development post-disposal. Temporal variability of communities collected at the
      disposal station post-cessation was higher than during years of disposal, when
      temporally stable dominance patterns of disturbance-tolerant species had
      established. Alterations of community structure post-disturbance reflected
      successional changes possibly driven by facilitation. Subtle faunistic changes at
      the Liverpool Bay disposal site indicate that the near-field effects of the
      disposal of sewage sludge were small and therefore could be considered
      environmentally acceptable.

PMID- 16979668
TI  - Joint FAO/WHO/IOC activities to provide scientific advice on marine biotoxins
      (research report).
AB  - The Joint FAO/WHO/IOC ad hoc Expert Consultation on Biotoxins in Molluscan
      Bivalves performed risk assessments for a number of biotoxins present in bivalve
      molluscs. For performing risk assessments, the Expert Consultation categorized
      the biotoxins into eight distinct groups based on chemical structure. The Expert
      Consultation established LOAELs for the azaspiracid (AZA), okadaic acid (OA),
      saxitoxin (STX), and domoic acid (DA) toxin groups. The derived provisional acute
      RfDs for the AZA, OA, STX, and DA toxin groups were 0.04 microg/kg bw, 0.33
      microg/kg bw, 0.7 microg/kg bw, and 100 microg/kg bw, respectively. For the
      yessotoxin (YTX) group, a NOAEL was established, based on animal studies.
      Applying a safety factor of 100, a provisional acute RfD of 50 microg/kg bw was
      suggested for the YTX group. The Expert Consultation considered that the database
      for cyclic imines, brevetoxins, and pectenotoxins was insufficient to establish
      provisional acute RfDs for these three toxin groups.

PMID- 16979669
TI  - The Bonn Agreement Aerial Surveillance programme: trends in North Sea oil
      pollution 1986-2004.
AB  - This paper examines the use of aerial surveillance activities conducted in the
      North Sea region of Europe since 1986 to assess trends in levels of oil inputs
      into the marine environment, both across the whole region and within the waters
      of the different coastal states. It makes use of data collected under the aegis
      of the 1969 Bonn Agreement through its Annual Reports on Aerial Surveillance and
      examines developments in surveillance methods and technology which have led to
      improvements in the detection of oil spills, even during the hours of darkness.
      The paper then examines country specific data for the eight North Sea contracting
      parties to the Agreement to assess trends in oil spills in the region.

PMID- 16979670
TI  - The European Commission proposal for a marine strategy: lacking substance.
AB  - The European Commission's proposed Marine Strategy constitutes a highly
      inadequate approach to long-term protection of the European Seas. The main
      problem with the strategy is the restriction to a proposed directive in which
      only EU Member States are placed under obligation to develop their own
      environmental objectives and marine protection activity programmes. This
      'renationalisation' results in the exclusion of key policy areas like Common
      Agricultural Policy (CAP) and Common Fishery Policy in which the EU has
      centralised powers. Furthermore, there is no plan to refine EU environmental law
      relevant to marine protection and nor are there any provisions for the linking of
      EU-level action with the international conventions for the protection of the
      oceans.

PMID- 16979672
TI  - Challenges to global surveillance of disease patterns.
AB  - Surveillance systems for foodborne disease vary in capacity by country,
      especially for marine-related illnesses. Generally, the more developed the
      country is, the more funding that is put into its surveillance programs, but no
      country has an outstanding system that could serve as a model for all others. An
      additional problem is lack of consistency. Approaches to surveillance and
      available resources change over time, so that apparent trends may reflect more of
      an administrative function. Most countries have some passive system that allows
      data on foodborne illnesses to be sent to centralized authorities where summaries
      are generated. However, these depend on the uneven quality of the source data
      that vary according to the resources allocated at the local level. Active
      surveillance systems collect data targeted to answer specific epidemiological
      questions more efficiently, but at such a high cost that most countries do not
      have the resources, except on a occasional basis. There is also the issue of what
      to do with the collected data. There has to be a conscious effort to translate
      the problems identified from the surveillance programs to consider strategies for
      prevention and control of foodborne disease. Otherwise, there is little value in
      having these kinds of monitoring programs. Another problem is lack of
      coordination in surveillance systems between most countries, so that information
      can be rapidly and efficiently shared. That being said, surveillance over the
      years had generated much interesting information on how disease agents are
      transmitted through the food supply, and where contamination and growth by
      pathogens in the food production and preparation chain typically occur. In
      addition, attempts are being made to create regional networks in different parts
      of the world usually initiated by organizations like WHO and PAHO. The kinds of
      information collected and programs being introduced are discussed in examples
      taken from both the developed and less developed world, followed by a series of
      recommendations for improving surveillance on a global basis. A recent burden in
      the surveillance system is the potential for a deliberate attack on the food
      supply with agents not usually involved with foodborne illness. At least in the
      US, a major concern is for the rapid detection and containment of a massive
      contamination of the food supply.

PMID- 16979673
TI  - Field accumulative behavior of organochlorine pesticides. The role of crabs and
      sediment characteristics in coastal environments.
AB  - The influence of intertidal crab beds on the concentrations of organochlorine
      (OC) pesticides in sediment was studied in two different coastal environments in
      Argentina. Samples of male burrowing crabs (Chasmagnathus granulatus) were
      collected for this study. Our field data showed lower bioaccumulation of OC
      pesticides in crabs from sediments with a higher total organic carbon (TOC) and
      higher clay content. Thus, concentrations in crabs depend on the physico-chemical
      characteristics of the sediment where they live more than on the OC pesticide
      concentrations in the environment. The distribution patterns in sediment from
      inside and outside crab burrows were similar for both coastal areas being HCHs >
      or = gamma-chlordane > p,p'-DDE for San Antonio Bay (SAO), and HCHs > p,p'-DDE >
      or = gamma-chlordane for Mar Chiquita (MCh) coastal lagoon. OC pesticide
      concentrations in sediment were significantly lower inside than outside crab
      burrows, irrespective of the sediment physico-chemical characteristics due to the
      bioturbation activity of C. granulatus.

PMID- 16979675
TI  - The contribution of human rights to improving public health.

PMID- 16979674
TI  - Dexterity in cerebellar agenesis.
AB  - Given the well established role of the cerebellum in motor control, deficient
      motor performance during life time appears to be common in cerebellar agenesis.
      However, behavioural data on motor performance in living subjects with cerebellar
      agenesis are scarce. Dexterity during object manipulation was comparatively
      investigated in a 63-year old female with cerebellar agenesis and three healthy
      age- and gender-matched control subjects. Participants performed a transport task
      with an instrumented object and caught a weight that was dropped into a hand-held
      receptacle either expectedly from the opposite hand or unexpectedly from the
      experimenter's hand. Compared to healthy subjects, the subject with cerebellar
      agenesis generated greater grasping forces. For the transport task the patient
      showed a clear impairment of the predictive adjustment of grasping forces to the
      differential loading requirements of movement direction. For the weight-catching
      task, the patient established an accurate reactive mode of control when the
      weight was dropped unexpectedly. In case the weight was dropped expectedly from
      the opposite hand, predictive control mechanisms were severely disturbed in the
      subject with cerebellar agenesis. These data highlight the role of the cerebellum
      for predictive force control and are interpreted within the concept of internal
      models reflecting the causal relationship between actions and their consequences.

PMID- 16979677
TI  - Legal foundations of public health law and its role in meeting future challenges.

PMID- 16979678
TI  - Therapeutic applications of conotoxins that target the neuronal nicotinic
      acetylcholine receptor.
AB  - Pain therapeutics discovered by molecular mining of the expressed genome of
      Australian predatory cone snails are providing lead compounds for the treatment
      of neurological diseases such as multiple sclerosis, shingles, diabetic
      neuropathy and other painful neurological conditions. The high specificity
      exhibited by these novel compounds for neuronal receptors and ion channels in the
      brain and nervous system indicates the high degree of selectivity that this class
      of neuropeptides can be expected to show when used therapeutically in humans. A
      lead compound, ACV1 (conotoxin Vc1.1 from Conus victoriae), has entered Phase II
      clinical trials and is being developed for the treatment for neuropathic pain.
      ACV1 will be targeted initially for the treatment of sciatica, shingles and
      diabetic neuropathy. The compound is a 16 amino acid peptide [Sandall et al.,
      2003. A novel alpha-conotoxin identified by gene sequencing is active in
      suppressing the vascular response to selective stimulation of sensory nerves in
      vivo. Biochemistry 42, 6904-6911], an antagonist of neuronal nicotinic
      acetylcholine receptors. It has potent analgesic activity following subcutaneous
      or intramuscular administration in several preclinical animal models of human
      neuropathic pain [Satkunanathan et al., 2005. Alpha conotoxin Vc1.1 alleviates
      neuropathic pain and accelerates functional recovery of injured neurons. Brain.
      Res. 1059, 149-158]. ACV1 may act as an analgesic by decreasing ectopic
      excitation in sensory nerves. In addition ACV1 appears to accelerate the recovery
      of injured nerves and tissues.

PMID- 16979679
TI  - Experimental investigation of a thermoacoustic-Stirling refrigerator driven by a
      thermoacoustic-Stirling heat engine.
AB  - In this paper, a thermally-driven thermoacoustic refrigerator system without any
      moving part is reported. This refrigeration system consists of a thermoacoustic
      Stirling heat engine and a thermoacoustic-Stirling refrigerator; that is, the
      former is the driving source for the latter. Both the subsystems are designed to
      operate on traveling-wave mode. In the experiment, it was found that the DC-flows
      had significant negative effect on the heat engine and the refrigerator. To
      suppress these DC-flows, two flexible membranes were inserted into the two
      subsystems and worked very well. Then extensive experiments were made to test the
      influence of different parameters on refrigeration performance of the whole
      system. The system has so far achieved a no-load temperature of -65 degrees C, a
      cooling capacity of about 270 W at -20 degrees C and 405 W at 0 degrees C; in
      fact, the result showed a good prospect of the refrigeration system in room
      temperature cooling such as food refrigeration and air-conditioning.

PMID- 16979680
TI  - Eight-channel ultrasonic device for non-invasive quality evaluation in packed
      milk.
AB  - An eight-channel ultrasonic detecting device for microbiological quality
      evaluation of packed liquid foods is presented in this paper. This device makes
      possible a non-invasive detection of the microbial growth in liquid foods with no
      need to open the carton-based packages where they are contained. Thermal and
      humidity stabilization are required inside the measuring chamber. The changes in
      the liquid media produced by the microorganism growth induce variations in the
      ultrasonic propagation parameters giving a non-invasive evidence of the
      developing contamination. For that purpose, the amplitude and time of flight of
      an ultrasonic 800kHz tone burst travelling through an UHT milk pack are analysed.
      Inoculated and sterile packs were tested to evaluate the performance of this new
      non-invasive ultrasonic microbiological quality sensor.

PMID- 16979681
TI  - An arginine-to-proline mutation in a domain with undefined functions within the
      helicase protein (Nsp13) is lethal to the coronavirus infectious bronchitis virus
      in cultured cells.
AB  - Genetic manipulation of the RNA genomes by reverse genetics is a powerful tool to
      study the molecular biology and pathogenesis of RNA viruses. During construction
      of an infectious clone from a Vero cell-adapted coronavirus infectious bronchitis
      virus (IBV), we found that a G-C point mutation at nucleotide position 15526,
      causing Arg-to-Pro mutation at amino acid position 132 of the helicase protein,
      is lethal to the infectivity of IBV on Vero cells. When the in vitro-synthesized
      full-length transcripts containing this mutation were introduced into Vero cells,
      no infectious virus was rescued. Upon correction of the mutation, infectious
      virus was recovered. Further characterization of the in vitro-synthesized full
      length transcripts containing the G15526C mutation demonstrated that this
      mutation may block the transcription of subgenomic RNAs. Substitution mutation of
      the Arg132 residue to a positively charged amino acid Lys affected neither the
      infectivity of the in vitro-synthesized transcripts nor the growth properties of
      the rescued virus. However, mutation of the Arg132 residue to Leu, a conserved
      residue in other coronaviruses at the same position, reduced the recovery rate of
      the in vitro-synthesized transcripts. The recovered mutant virus showed much
      smaller-sized plaques. On the contrary, a G-C and a G-A point mutations at
      nucleotide positions 4330 and 9230, respectively, causing Glu-Gln and Gly-Glu
      mutations in or near the catalytic centers of the papain-like (Nsp3) and 3C-like
      (Nsp5) proteinases, did not show detectable detrimental effect on the rescue of
      infectious viruses and the infectivity of the rescued viruses.

PMID- 16979682
TI  - Template requirements for recognition and copying by Sindbis virus RNA-dependent
      RNA polymerase.
AB  - The Sindbis virus (SIN) nonstructural protein nsP4 possesses the RNA-dependent
      RNA polymerase activity required for the replication of the SIN genome and
      transcription of a subgenomic mRNA during infection. Isolation of this protein
      from other viral components of the RNA synthetic complex allowed the
      characterization of template requirements for nsP4-mediated genome replication.
      The major findings of this study are: (i) in the absence of other viral proteins
      nsP4 is capable of copying SIN plus- and minus-strand templates, but does not
      transcribe subgenomic RNA; (ii) mutations in the 3' conserved sequence element
      and poly(A) tail of the plus-strand template prevent nsP4-mediated de novo
      initiation of minus-strand RNA synthesis; (iii) nsP4-dependent terminal addition
      of nucleotides occurs on template RNA possessing certain mutations in the 3'CSE
      and polyadenylate tail ; (iv) nsP4 is capable of minus-strand synthesis
      independent of the sequence at the 5' end of the template; (v) an A-U rich
      sequence in the 3'CSE represents a binding site for a replicase component,
      probably nsP4; (vi) plus-strand genomic RNA synthesis is dependent on the 3' end
      of the minus-strand template. These studies begin to define the specific
      interactions with the viral RNA templates mediated by individual components of
      the viral replication complex and suggest a model for ternary complex formation
      during the initiation of minus-strand RNA synthesis.

PMID- 16979683
TI  - Variola virus IL-18 binding protein interacts with three human IL-18 residues
      that are part of a binding site for human IL-18 receptor alpha subunit.
AB  - Interleukin-18 (IL-18) plays an important role in host defense against microbial
      pathogens. Many poxviruses encode homologous IL-18 binding proteins (IL-18BP)
      that neutralize IL-18 activity. Here, we examined whether IL-18BP neutralizes IL
      18 activity by binding to the same region of IL-18 where IL-18 receptor (IL-18R)
      binds. We introduced alanine substitutions to known receptor binding sites of
      human IL-18 and found that only the substitution of Leu5 reduced the binding
      affinity of IL-18 with IL-18BP of variola virus (varvIL-18BP) by more than 4
      fold. The substitutions of Lys53 and Ser55, which were not previously known to be
      part of the receptor binding site but that are spatially adjacent to Leu5,
      reduced the binding affinity to varvIL-18BP by approximately 100- and 7-fold,
      respectively. These two substitutions also reduced the binding affinity with
      human IL-18R alpha subunit (hIL-18Ralpha) by 4- and 2-fold, respectively.
      Altogether, our data show that varvIL-18BP prevents IL-18 from binding to IL-18R
      by interacting with three residues that are part of the binding site for hIL
      18Ralpha.

PMID- 16979684
TI  - Suppressor of RNA silencing encoded by Tomato yellow leaf curl virus-Israel.
AB  - The Israeli isolate of Tomato yellow leaf curl geminivirus (TYLCV-Is) is a major
      tomato pathogen, causing extensive crop losses both in the New and Old World.
      Surprisingly, however, little is known about the molecular mechanisms of TYLCV-Is
      interactions with tomato cells. Here, we have identified a TYLCV-Is protein, V2,
      which acts as a suppressor of RNA silencing and which is unrelated to presently
      known viral suppressors. Specifically, V2, but not other proteins of TYLCV-Is,
      inhibited RNA silencing of a reporter transgene, GFP. This inhibition elevated
      the cellular levels of the GFP transcript and the GFP protein, but it had no
      apparent effect on the accumulation of GFP-specific short interfering RNAs
      (siRNAs), suggesting that TYLCV-Is V2 targets a step in the RNA silencing pathway
      which is subsequent to the Dicer-mediated cleavage of dsRNA. Visualization of the
      sub-cellular localization of TYLCV-Is V2 in plant protoplasts and tissues showed
      that this protein is associated with cytoplasmic strands and inclusion bodies in
      the cortical regions of the cell.

PMID- 16979685
TI  - Illusory scene distortion occurs during perceived self-rotation in roll.
AB  - We report a novel illusory distortion of the visual scene, which became apparent
      during both: (i) observer rotation inside a furnished stationary room; and (ii)
      room rotation about the stationary observer. While this distortion had several
      manifestations, the most common experience was that scenery near fixation
      appeared to sometimes lead and other times lag more peripheral scenery. Across a
      series of experiments, we eliminated explanations based on eye-movements,
      distance misperception, peripheral aliasing, differential motion sensitivity and
      adaptation. We found that these illusory scene distortions occurred only when the
      observer perceived (real or illusory) changes in self-tilt and maintained a
      stable fixation.

PMID- 16979686
TI  - Defective development of photoreceptor membranes in a mouse model of recessive
      retinal degeneration.
AB  - Retinal neurodegeneration occurs in several inherited diseases. Some of the most
      severe disease alleles involve mutations at the C-terminus of rhodopsin, but in
      no case is the pathogenic mechanism leading to cell death well understood. We
      have examined a mouse model of recessive retinal degeneration caused by a knock
      in of a human rhodopsin-EGFP fusion gene (hrhoG/hrhoG) at the rhodopsin locus.
      Whereas heterozygous mutant mice were indistinguishable from control mice,
      homozygous mutant mice had retinal degeneration. We hypothesized that
      degeneration might be due to aberrant rhodopsin signaling; however, inhibiting
      signaling by rearing mice in total darkness had no effect on the rate of
      degeneration. Using confocal and electron microscopy, we identified the
      fundamental defect as failed biogenesis of disk membranes, which is observed at
      the earliest stages of outer segment development. These results reveal that in
      addition to its role in transport and sorting of rhodopsin to disk membranes,
      rhodopsin is also essential for formation of disks.

PMID- 16979687
TI  - Perceived size and perceived distance of targets viewed from between the legs:
      evidence for proprioceptive theory.
AB  - We investigated, using three comparisons, perceived size and perceived distance
      of targets seen from between the legs. Five targets, varying from 32 to 163 cm in
      height, were presented at viewing distances of 2.5-45 m, and a total of 90
      observers verbally judged the perceived size and perceived distance of each
      target. In comparison 1, 15 observers inverted their heads upside down and saw
      the targets between their own legs; another 15 observers viewed them while being
      erect on the ground. The results showed that inverting the head lowered the
      degree of size constancy and compressed the scale for distance. To examine
      whether these results were due to an inversion of retinal-image or body
      orientation, comparisons 2 and 3 were performed. In comparison 2, 15 observers
      stood upright and saw the targets with prism goggles that rotated the visual
      field 180 degrees , while other 15 observers stood upright, but viewed the
      targets with a hollow frame lacking the prisms. The results showed that, in both
      goggle conditions, size constancy prevailed and perceived distance was a linear
      function of physical distance. In comparison 3, 15 observers wore the 180 degrees
      rotation goggles and viewed the targets by bending their heads forwardly, and the
      other 15 observers viewed them while wearing hollow goggles and lying on the
      belly. The results showed a low degree of size constancy and compressed the scale
      for distance. Therefore, it is suggested that perceived size and perceived
      distance are affected by an inversion of body orientation, not of retinal image
      orientation. When path analysis and partial correlation analysis were applied to
      the whole data, perceived size was found to be independent of perceived distance.
      These results supported the direct perception model, rather than the apparent
      distance model.

PMID- 16979688
TI  - A link between perceptual learning, adaptation and sleep.
AB  - Between-sessions gains in the texture discrimination task have been attributed to
      memory consolidation. A strong dependence of consolidation on sleep was suggested
      though not always supported by experimental results. Here we suggest that the
      interaction between consolidation and sleep depends on the adaptation level
      obtained during the training session. We find that both discrimination thresholds
      and learning depend on the number of trials used during training, with more
      trials producing higher discrimination thresholds due to suppressive processes
      related to adaptation. In addition, while learning benefits from increasing
      number of trials, a further increase in number of trials reduces learning.
      Consolidation may benefit from between-session sleep in the adapted states.

PMID- 16979689
TI  - Probing rhodopsin-transducin interaction using Drosophila Rh1-bovine rhodopsin
      chimeras.
AB  - Invertebrate and vertebrate rhodopsins share a low degree of homology and are
      coupled to G-proteins from different families. Here we explore the utility of fly
      expressed chimeras between Drosophila rhodopsin Rh1 and bovine rhodopsin (Rho) to
      probe the interactions between the invertebrate and vertebrate visual pigments
      and their cognate G-proteins. Chimeric Rh1 pigments carrying individual
      substitutions of the cytoplasmic loops C2 and C3 and the C-terminus with the
      corresponding regions of Rho retained the ability to stimulate phototranduction
      in Drosophila, but failed to activate transducin. Surprisingly, chimeric Rho
      containing the Rh1 C-terminus was fully capable of transducin activation,
      indicating that the C-terminal domain of vertebrate rhodopsins is not essential
      for the functional coupling to transducin.

PMID- 16979690
TI  - Exogenous attention and color perception: performance and appearance of
      saturation and hue.
AB  - Exogenous covert attention is an automatic, transient form of attention that can
      be triggered by sudden changes in the periphery. Here we test for the effects of
      attention on color perception. We used the methodology developed by Carrasco,
      Ling, and Read [Carrasco, M., Ling, S., & Read, S. (2004). Attention alters
      appearance. Nature Neuroscience, 7 (3) 308-313] to explore the effects of
      exogenous attention on appearance of saturation (Experiment 1) and of hue
      (Experiment 2). We also tested orientation discrimination performance for single
      stimuli defined by saturation or hue (Experiment 3). The results indicate that
      attention increases apparent saturation, but does not change apparent hue,
      notwithstanding the fact that it improves orientation discrimination for both
      saturation and hue stimuli.

PMID- 16979691
TI  - NMR analysis of rhodopsin-transducin interactions.
AB  - Heterotrimeric G-protein activation by an agonist-stimulated G-protein coupled
      receptor (R*) requires the propagation of structural signals from the receptor
      interacting surfaces to the guanine nucleotide-binding pocket. Employing high
      resolution NMR methods, we are probing heterotrimer-associated and rhodopsin
      stimulated changes in an isotope-labeled G-protein alpha-subunit (G(alpha)). A
      key aspect of the work involves the trapping and interrogation of discrete R*
      bound conformations of G(alpha). Our results demonstrate that functionally
      important changes in G(alpha) structure and dynamics can be detected and
      characterized by NMR, enabling the generation of robust models for the global and
      local structural changes accompanying signal transfer from R* to the G-protein.

PMID- 16979692
TI  - Photoreceptor vitality in organotypic cultures of mature vertebrate retinas
      validated by light-dependent molecular movements.
AB  - Vertebrate photoreceptor cells are polarized neurons highly specialized for light
      absorption and visual signal transduction. Photoreceptor cells consist of the
      light sensitive outer segment and the biosynthetic active inner segment linked by
      a slender connecting cilium. The function of mature photoreceptor cells is
      strictly dependent on this compartmentalization which is maintained in the
      specialized retinal environment. To keep this fragile morphologic and functional
      composition for further cell biological studies and treatments we established
      organotypic retina cultures of mature mice and Xenopus laevis. The organotypic
      retina cultures of both model organisms are created as co-cultures of the retina
      and the pigment epithelium, still attached to outer segments of the photoreceptor
      cells. To demonstrate the suitability of the culture system for physiological
      analyses we performed apoptotic cell death analyses and verified photoreceptor
      viability. Furthermore, light-dependent bidirectional movements of arrestin and
      transducin in photoreceptors in vivo and in the retinal cultures were
      indistinguishable indicating normal photoreceptor cell-biologic function in
      organotypic cultures. Our established culture systems allow the analysis of
      mature photoreceptor cells and their accessibility to treatments, characteristic
      for common cell culture. Furthermore, this culturing technique also provides an
      appropriate system for gene delivery to retinal cells and will serve to simulate
      gene therapeutic approaches prior to difficult and time-consuming in vivo
      experiments.

PMID- 16979693
TI  - Neural evidence for intermediate representations in object recognition.
AB  - The lateral occipital complex (LOC), a cortical region critical for human object
      recognition, has been shown to primarily code the shape, rather than the surface
      properties, of an object. But what aspects of shape? Using an fMRI-adaptation
      (fMRI-a) paradigm in which subjects judged whether two contour-deleted images of
      objects were the same or different exemplars, virtually all the adaptation in LOC
      [especially in LOC's most anterior portion (pFs)] could be attributed to
      repetition of the parts, almost none to the repetition of local image features,
      such as lines or vertices, templates, or basic- or subordinate-level concepts of
      the object. These results support the hypothesis that the neural representation
      of shape in LOC is an intermediate one, encoding the parts of an object.

PMID- 16979694
TI  - Parameters from a new kinetic equation to evaluate activated carbons efficiency
      for water treatment.
AB  - The fractal dimension of some commercial activated carbon (AC) was determined in
      the micro-, meso- and macropore range using mercury porosimetry and N(2)
      adsorption data. We studied the kinetic of adsorption of phenol, tannic acid and
      melanoidin on those ACs. The typical concentration-time profiles obtained here
      could be very well fitted by a general fractal kinetics equation
      q(n,alpha)(t)=q(e)[1-(1+(n-1)(t/tau(n,alpha))(alpha))(-1/(n-1))] deduced from
      recently new methods of analysis of reaction kinetics and relaxation. The
      parameter n is the reaction order, alpha is a fractional time index, q(e)
      measures the maximal quantity of solute adsorbed, and a "half-reaction time",
      tau(1/2), can be calculated, which is the time necessary to reach half of the
      equilibrium. The adsorption process on AC is clearly a heterogeneous process,
      taking place at the liquid-solid boundary, and the diffusion process occurs in a
      complex matrix with a fractal architecture as demonstrated here. In fact, these
      systems belong to what has been called "complex systems" and the fractal kinetic,
      which has been extensively applied to biophysics, can be a useful theoretical
      tool for study adsorption processes.

PMID- 16979695
TI  - Synergy of ozonation and photocatalysis to mineralize low concentration 2,4
      dichlorophenoxyacetic acid in aqueous solution.
AB  - Concentration of 2,4-dichlorophenoxyacetic acid (2,4-D) may affect its
      degradation kinetics in advanced oxidation systems, and combinations of two or
      more systems can be more effective for its mineralization at low concentration
      levels. Degradations and mineralizations of 0.045mM 2,4-D using O(3), O(3)/UV,
      UV/TiO(2) and O(3)/UV/TiO(2) systems were compared, and influence of reaction
      temperature on the mineralization in O(3)/UV/TiO(2) system was investigated. 2,4
      D degradations by O(3), O(3)/UV and UV/TiO(2) systems were similar to the results
      of earlier investigations with higher 2,4-D concentrations. The degradations and
      total organic carbon (TOC) removals in the four systems were well described by
      the first-order reaction kinetics. The degradation and removal were greatly
      enhanced in O(3)/UV/TiO(2) system, and further enhancements were observed with
      larger O(3) supplies. The enhancements were attributed to hydroxyl radical (()OH)
      generation from more than one reaction pathway. The degradation and removal in
      O(3)/UV/TiO(2) system were very efficient with reaction temperature fixed at 20
      degrees C. It was suspected that reaction temperature might have influenced ()OH
      generation in the system, which needs further attention.

PMID- 16979696
TI  - Risk assessment of trace elements in the stomach contents of Indo-Pacific
      Humpback Dolphins and Finless Porpoises in Hong Kong waters.
AB  - The potential health risks due to inorganic substances, mainly metals, was
      evaluated for the two resident marine mammals in Hong Kong, the Indo-Pacific
      Humpback Dolphin (Sousa chinensis) and the Finless Porpoise (Neophocaena
      phocaenoides). The stomachs from the carcasses of twelve stranded dolphins and
      fifteen stranded porpoises were collected and the contents examined.
      Concentrations of thirteen trace elements (Ag, As, Cd, Co, Cr, Cs, Cu, Hg, Mn,
      Ni, Se, V and Zn) were determined by inductively coupled plasma mass spectrometer
      (ICP-MS). An assessment of risks of adverse effects was undertaken using two
      toxicity guideline values, namely the Reference Dose (RfD), commonly used in
      human health risk assessment, and the Toxicity Reference Value (TRV), based on
      terrestrial mammal data. The levels of trace metals in stomach contents of
      dolphins and porpoises were found to be similar. Risk quotients (RQ) calculated
      for the trace elements showed that risks to the dolphins and porpoises were
      generally low and within safe limits using the values based on the TRV, which are
      less conservative than those based on the RfD values. Using the RfD-based values
      the risks associated with arsenic, cadmium, chromium, copper, nickel and mercury
      were comparatively higher. The highest RQ was associated with arsenic, however,
      most of the arsenic in marine organisms should be in the non-toxic organic form,
      and thus the calculated risk is likely to be overestimated.

PMID- 16979697
TI  - Influence of initial pH on bioleaching of heavy metals from contaminated soil
      employing indigenous Acidithiobacillus thiooxidans.
AB  - Bioleaching of heavy metals from contaminated soil was carried out employing
      indigenous sulfur oxidizing bacterium Acidithiobacillus thiooxidans. Experiments
      were carried out to assess the influence of initial pH of the system on
      bioleaching of chromium, zinc, copper, lead and cadmium from metal contaminated
      soil. pH at the end of four weeks of bioleaching at different initial pH of 3-7
      was between 0.9 and 1.3, ORP between 567 and 617mV and sulfate production was in
      the range of 6090-8418mgl(-1). Chromium, zinc, copper, lead and cadmium
      solubilization ranged from "59% to 98%" at different initial pH. A. thiooxidans
      was not affected by the increasing pH of the bioleaching system towards neutral
      and it was able to utilize elemental sulfur. The results of the present study are
      encouraging to develop the bioleaching process for decontamination of heavy metal
      contaminated soil.

PMID- 16979698
TI  - Synchronous prostate stromal sarcoma and gastrointestinal stromal tumor of
      rectum: case report and review of the literature.
AB  - We report a case of prostate stromal sarcoma with initial presentation of
      obstructive voiding symptoms. The synchronous rectal gastrointestinal stromal
      tumor was also finally discovered. The patient underwent pelvic exenteration as
      the choice of treatment. Synchronous prostate stromal sarcoma and rectal
      gastrointestinal stromal tumor is an extremely rare disease in the literature
      view.

PMID- 16979699
TI  - Laparoscopic partial adrenalectomy for aldosterone-producing adenomas with
      needlescopic instruments.
AB  - INTRODUCTION: Laparoscopic total adrenalectomy is the treatment of choice for
      aldosterone-producing adenomas (APAs). There have not been many reports of
      laparoscopic partial adrenalectomy, although this procedure offers benefits to
      patients with suspected bilateral APAs or an APA in a solitary adrenal gland. We
      describe the feasibility of a novel technique of laparoscopic partial
      adrenalectomy for APA solely using 2-mm working instruments and a 5 to 10-mm
      telescope. TECHNICAL CONSIDERATIONS: Six unilateral and two bilateral partial
      adrenalectomies were performed laparoscopically. Only one umbilical 12-mm port
      for the telescope and two (for left adenomas) or three (for right adenomas)
      subcostal 2-mm working ports were used. Hemostasis and transection of adrenal
      tissues were performed using a 2-mm mini-bipolar coagulator and 2-mm scissors.
      RESULTS: All laparoscopic operations were successfully performed using only 2-mm
      working instruments and a 5 or 10-mm 30 degree telescope with no intraoperative
      or postoperative complications. Blood loss was minimal, and the operative times
      were comparable to those of previous reports. All patients had low pain scores,
      required minimal amounts of narcotics postoperatively, and reported excellent
      cosmetic results for the wounds. The pathologic examinations confirmed complete
      excision of all adenomas with intact capsules. The plasma aldosterone
      concentrations and renin activities returned to normal ranges postoperatively in
      all patients. At a mean follow-up of 25 months (range 13 to 48), 7 (87.5%) were
      cured of their hypertension and 1 had the hypertensive medications significantly
      reduced. CONCLUSIONS: Laparoscopic partial adrenalectomy for APAs using 2-mm
      working instruments and a 5 to 10-mm telescope is a safe and effective treatment
      alternative.

PMID- 16979700
TI  - Segmental ischemia of testis secondary to intermittent testicular torsion.

PMID- 16979701
TI  - Through the eyes of women: the partners' perspective on tadalafil.
AB  - OBJECTIVES: To evaluate patient and female partner responses on the efficacy of,
      and overall satisfaction with, tadalafil to treat erectile dysfunction using
      sexual encounter profile (SEP) diaries. METHODS: Data were pooled from four
      double-blind, placebo-controlled, 12-week trials that included 746 couples.
      Patients were randomized to placebo or tadalafil 10 or 20 mg. Efficacy was
      evaluated by the mean per-patient/per-partner percentage of "yes" responses to
      patient SEP questions 1, 2, and 5 and partner SEP questions 1 to 3 (erection
      achievement, penetration, and overall satisfaction with the sexual experience,
      respectively) for tadalafil versus placebo. For each SEP question, the number of
      postbaseline intercourse attempts when each couple agreed on the outcome was
      tabulated and divided by the total number of postbaseline attempts to calculate
      the mean percentage of agreement by couple. The overall satisfaction with
      successful postbaseline intercourse attempts was determined. RESULTS: Tadalafil
      significantly improved the responses for the patient and partner-evaluated SEP
      questions (P <0.001, both doses versus placebo). Partners tended to report
      greater overall satisfaction than patients at baseline and postbaseline. The mean
      percentage of agreement by couple was approximately 98% for erection achievement
      and penetration and 85% for overall satisfaction. For successful intercourse
      attempts, patients and partners treated with tadalafil reported more overall
      satisfaction than those treated with placebo (P <0.05, tadalafil versus placebo
      comparisons). CONCLUSIONS: Partners reported significantly improved overall
      sexual satisfaction and corroborated the man's report of improved erections and
      penetration ability with tadalafil 10 mg or 20 mg. Men reported improved erection
      achievement, penetration, and overall satisfaction with the sexual experience
      after taking tadalafil.

PMID- 16979702
TI  - Renal artery pseudoaneurysm of infectious etiology: a life-threatening
      complication after renal transplantation.

PMID- 16979703
TI  - V-V plasty: a new technique for providing a resilient skin-lined opening for the
      Mitrofanoff stoma.
AB  - Stomal stenosis is a frequent complication after creation of a Mitrofanoff stoma
      for urinary diversion. We describe a new technique for achieving a skin-lined
      stoma opening that is easy to construct and decreases the risk of stenosis in the
      long term.

PMID- 16979704
TI  - Effect of sildenafil citrate treatment on serum dehydroepiandrosterone sulfate
      levels in patients with erectile dysfunction.
AB  - OBJECTIVES: To investigate the effect of sildenafil citrate treatment on serum
      dehydroepiandrosterone sulfate (DHEAS) levels in patients with erectile
      dysfunction (ED). METHODS: A total of 124 men with a mean age of 45.9 years were
      included in the study. Group 1 consisted of 78 patients with ED, as determined by
      the Sexual Health Inventory of Male (SHIM) scale (score less than 21). Group 2
      consisted of 46 healthy men with a SHIM score of 21 or greater. The 78 patients
      with ED took 100 mg sildenafil citrate at least eight times in 1 month. The SHIM
      scale was administered and serum DHEAS levels measured before and after treatment
      in the ED group. The serum DHEAS levels were also measured in the control group.
      The treatment response was defined as positive if the SHIM score was 21 or
      greater after sildenafil administration. RESULTS: At the end of sildenafil
      citrate treatment, the serum DHEAS levels and SHIM scores had increased
      significantly in the ED group (P = 0.013 and P = 0.001, respectively). In groups
      1 and 2, the mean pretreatment serum DHEAS level of the men younger than 50 years
      old was 200.1 +/- 77.9 and 279.4 +/- 125.4 microg/dL, respectively (P = 0.013).
      The elevation of the serum DHEAS levels and SHIM scores was more significant in
      the sildenafil responders (P = 0.002 and P = 0.001), respectively. CONCLUSIONS:
      Serum DHEAS levels were significantly greater in the patients younger than 50
      years old than in the older patients in the ED group. The serum DHEAS levels
      increased significantly after sildenafil citrate treatment in the ED group
      (especially in the younger men). Also, patient age was an important factor
      affecting the sildenafil citrate response.

PMID- 16979705
TI  - Expression of clusterin in prostate cancer correlates with Gleason score but not
      with prognosis in patients undergoing radical prostatectomy without neoadjuvant
      hormonal therapy.
AB  - OBJECTIVES: To determine whether the expression level of clusterin in prostate
      cancer could be used as a prognostic predictor in patients who have undergone
      radical prostatectomy (RP). METHODS: This study included 172 consecutive patients
      undergoing RP for clinically organ-confined prostate cancer without neoadjuvant
      hormonal therapy. Immunohistochemical staining was performed in RP specimens
      obtained from these patients to evaluate the expression level of clusterin
      protein. The cell proliferative activities and apoptotic features in these
      specimens were investigated using Ki-67 immunostaining and terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay,
      respectively. RESULTS: Varying levels of clusterin expression were noted in 169
      of 172 prostate cancer specimens; 32 of the 172 normal prostatic tissue specimens
      did not exhibit any clusterin staining. Clusterin expression in prostate cancer
      tissue was significantly related to the Gleason score, but not to the other
      parameters, including age, serum prostate-specific antigen level, pathologic
      stage, perineural invasion, tumor volume, and lymph node metastasis. In addition,
      cell proliferative activity in the prostate cancer specimens was significantly
      associated with clusterin expression; however, no correlation was found between
      the apoptotic index and clusterin expression. In this series, 34 (19.8%) of 172
      patients developed biochemical recurrence. No significant difference was found in
      biochemical/recurrence-free survival between patients with strong clusterin
      expression and those with weak expression. CONCLUSIONS: Despite its detection in
      most prostate cancer tissue, clusterin expression failed to show a significant
      association with prognosis in patients undergoing RP without neoadjuvant hormonal
      therapy. This suggests a limited role for clusterin in the progression of
      clinically organ-confined prostate cancer in the absence of proapoptotic stimuli.

PMID- 16979706
TI  - Laparoscopic cytoreductive nephrectomy: the M. D. Anderson Cancer Center
      experience.
AB  - OBJECTIVES: Cytoreductive nephrectomy (CN) is an integral component in treating
      patients with metastatic renal cell carcinoma. Critics of CN argue that
      perioperative morbidity or postoperative disease progression may preclude
      patients from receiving systemic therapy. Laparoscopic cytoreductive nephrectomy
      (LCN) may allow for reduced morbidity and may increase the likelihood of patients
      receiving systemic therapy. METHODS: From April 2001 to March 2005, 38 patients
      underwent LCN at our institution. We evaluated perioperative parameters such as
      demographics, blood loss, operative time, complications, follow-up time, interval
      to systemic therapy, and survival. A contemporary open cytoreductive surgery
      group was evaluated for comparison. RESULTS: The median patient age was 62 years
      (range 41 to 82). Most patients had a performance status of 1 or less. The median
      operative time was 188 minutes, and the median blood loss was 175 mL. All
      specimens were removed intact. The median tumor size was 8 cm (range 3.5 to 14).
      The median hospitalization was 3 days. Two major (5.7%) and four minor (11.4%)
      complications occurred, but no perioperative mortality. Postoperatively, 97.4% of
      patients were eligible for, or received, systemic therapy at a median of 41 days.
      The overall median survival was 18.1 months. In contrast to open CN, LCN resulted
      in decreased blood loss and hospital stay, with no differences in complications,
      operative time, or interval to systemic therapy. CONCLUSIONS: LCN is a safe and
      effective surgical approach for select patients with metastatic renal cell
      carcinoma. Our results have indicated that with proper patient selection, LCN is
      feasible, morbidity is minimized, and systemic therapy is delivered in a timely
      fashion.

PMID- 16979707
TI  - Ultrasound-guided percutaneous nephrostomy performed by urologists: 10-year
      experience.
AB  - OBJECTIVES: To assess the safety, feasibility, and effectiveness of percutaneous
      nephrostomy tube (PNT) insertion performed solely by a urologist on an outpatient
      basis. We present our relevant 10-year experience. METHODS: From 1996 to 2005,
      650 PNT insertions were performed in 530 patients (356 men and 174 women), aged
      39 to 94 years (mean 67.4). All patients were referred to our outpatient
      department. PNT placement was performed under local anesthesia by a consultant
      urologist or registrar during regular work hours or during on-call duty. Early
      complications within 30 days of PNT insertion were recorded. RESULTS: Primary
      successful PNT insertion was recorded in 615 (94.6%) of the 650 procedures.
      Follow-up data up to 30 days were available for 545 PNT placements (83.8%). Of
      the 650 PNT insertions, 22 (3.3%) major immediate complications were encountered.
      In 4 patients, laparotomy was performed for surgical exploration of hemorrhage (3
      patients) or choleperitoneum, resulting in nephrectomy (1 patient). In 5 (0.8%)
      of 615 successful PNT procedures, we recorded septicemia, which resulted in 2
      deaths. In 1 more case (0.1%), the nephrostomy tube was misplaced into the
      inferior vena cava. Minor complications within the follow-up period were recorded
      in 24 (4.5%) of 545 cases. The complication rate did not differ significantly
      between the consultants and registrars or whether PNT insertion was performed
      during regular work hours or during on-call duty. CONCLUSIONS: Ultrasound-guided
      PNT insertion performed solely by a urologist is a safe, feasible, and efficient
      procedure, regardless of the operator's experience.

PMID- 16979708
TI  - Open partial nephrectomy with selective renal parenchymal control: a new reliable
      clamp.
AB  - We describe our experience of open partial nephrectomy with a parenchymal clamp,
      the Reni-Clamp, in 30 patients from January 2002 to May 2005. The mean operative
      and clamping time was 150 and 27 minutes, respectively, and the blood loss was
      150 mL. The Reni-Clamp enabled us to perform partial nephrectomy safely in all
      cases of polar or external edge renal tumor.

PMID- 16979709
TI  - Robotic-assisted laparoscopic ureteroureterostomy in an adolescent with an
      obstructed upper pole system and crossed renal ectopia with fusion.
AB  - Ureteropelvic junction obstruction (UPJO) in crossed renal ectopia with fusion is
      a rare condition. Management of UPJO occurring in ectopic kidneys generally
      requires open surgical reconstruction. Experience with minimally invasive
      techniques is minimal for repair of UPJO in ectopic kidneys. We report what we
      believe to be the first documented case of laparoscopic ureteroureterostomy with
      the da Vinci robotic system in an adolescent with an obstructed upper pole system
      and crossed renal ectopia with fusion.

PMID- 16979710
TI  - Multifocal penile epithelioid hemangioendothelioma masquerading as superficial
      penile vein thrombosis.
AB  - A 42-year-old man presented with a progressively painful mass of the penile shaft
      that clinically resembled superficial penile vein thrombosis. The patient's
      symptoms were refractory to conservative therapy, and surgical excision revealed
      multifocal penile epithelioid hemangioendothelioma. He had no evidence of
      metastatic disease and was well 1 year after excision. Vascular neoplasms should
      be included in the differential diagnosis of painful penile masses and penile
      thrombophlebitis. To our knowledge, this is only the second reported case of
      multifocal penile epithelioid hemangioendothelioma.

PMID- 16979711
TI  - Cardiac and hepatic seed implant embolization after prostate brachytherapy.
AB  - Prostate brachytherapy seed implants occasionally embolize to lungs because of
      their small size. They may lodge in the right cardiac cavities before reaching
      the pulmonary arteries and lungs. A rare instance of seed migration to the
      coronary artery through an existing right-to-left cardiac shunt or patent foramen
      ovale has also been reported. I present a case of seed implant relocation to the
      heart and left hepatic lobe by way of presumed different venous pathways
      represented by the periprostatic and hemorrhoidal venous plexuses, respectively.

PMID- 16979712
TI  - Rare case of ectopic duplicated megaureter with dysplastic upper kidney moiety
      opening into ipsilateral ejaculatory duct.
AB  - A rare case of left mesonephric duct malformation consisting of a duplicated
      ectopic megaureter opening into the ejaculatory duct and ipsilateral upper moiety
      cystic renal dysplasia is reported to increase awareness among urologists and
      radiologists of this entity. Magnetic resonance imaging has been shown to be an
      excellent diagnostic tool for tracking of the trajectory of the ectopic ureter,
      thereby obviating the need for other invasive diagnostic techniques and
      permitting surgical correction of the anomaly. The embryology, clinical features,
      and diagnostic and therapeutic aspects of this rare malformation are presented.

PMID- 16979713
TI  - Synchronous unilateral renal cell carcinoma and Kimura disease of the kidney.
AB  - Kimura disease (KD) is a rare, benign, chronic inflammatory disorder most often
      found in young Asian males that can simulate a neoplasm. We report a case of
      renal cell carcinoma and KD within the same kidney. To our knowledge, this is the
      first reported case of KD involving the kidney confirmed pathologically, as well
      as the first association of KD with renal cell carcinoma.

PMID- 16979714
TI  - Use of Avagard in pediatric urologic procedures.
AB  - OBJECTIVES: To evaluate the use of Avagard compared with a hand-brush scrub
      preparation by the urologist in preparation for inpatient and outpatient
      pediatric urologic operations. Avagard (chlorhexidine gluconate 1% solution and
      ethyl alcohol 61% wt/wt) is a waterless, brushless, and scrubless hand antiseptic
      indicated as a replacement for traditional preoperative brush hand scrubbing.
      METHODS: We evaluated the first 550 patients for whom we used Avagard as a
      preoperative hand antiseptic and compared them with the last 550 consecutive
      patients for whom we performed traditional antiseptic-impregnated hand-brush
      scrubbing. All patients underwent pediatric urologic procedures. Patients were
      monitored postoperatively for signs of wound infection, and patients and the
      surgeon were monitored for side effects. A cost analysis was performed to compare
      the use of Avagard as a preoperative hand preparation with that of an antiseptic
      impregnated hand-brush. RESULTS: The incidence of wound infection was one in the
      Avagard group and two in the hand-scrub group, not a statistically significant
      difference. All wound infections were successfully treated with a single course
      of oral antibiotics without any long-term sequelae. No side effects for the
      patients or surgeon were noted, including skin irritations or allergic reactions
      in either group. The use of Avagard was more time efficient and cost effective.
      CONCLUSIONS: To our knowledge, this is the first study demonstrating that Avagard
      is a fast, effective, easy to apply, and safe surgical hand preparation for
      pediatric urologic surgery. Its use is cost effective, as well as time efficient,
      in relation to the traditional surgical scrub.

PMID- 16979715
TI  - Radical cystectomy with extended lymphadenectomy in the presence of a pelvic
      kidney.
AB  - The pelvic kidney represents the most common form of congenital renal ectopia.
      Because of its location, variable vasculature, and short ureteral length, the
      presence of a pelvic kidney in a patient undergoing radical cystectomy and pelvic
      lymphadenectomy creates unique technical challenges for the urologic surgeon. We
      describe a patient with a right pelvic kidney and invasive bladder cancer for
      whom radical cystectomy with extended pelvic iliac lymph node dissection and
      ileal conduit was performed.

PMID- 16979716
TI  - Long-term response with sunitinib for metastatic renal cell carcinoma.
AB  - A 65-year-old man with metastatic renal cell carcinoma developed progressive
      disease after treatment with interferon-alpha. He began treatment with sunitinib,
      a multitargeted tyrosine kinase inhibitor, on clinical trial. The patient
      achieved a partial response after two cycles of therapy, with a durable response
      continuing after 2 years of treatment. This case report illustrates the long-term
      response to sunitinib for patients with metastatic renal cell carcinoma.

PMID- 16979717
TI  - Primary carcinoid tumor in an ileal conduit.
AB  - Carcinoid tumors are neuroendocrine tumors that typically arise in the
      gastrointestinal tract. We present the case of a 74-year-old woman with a primary
      carcinoid tumor in an ileal conduit urinary diversion who presented with gross
      hematuria. We also provide a brief review of relevant reports. The patient
      subsequently underwent resection and replacement of her ileal conduit.

PMID- 16979718
TI  - Efficacy of sildenafil citrate in treatment of erectile dysfunction: impact of
      associated premature ejaculation and low desire.
AB  - OBJECTIVES: To assess the effect of premature ejaculation (PE) and low desire on
      the efficacy and satisfaction rate of sildenafil in the treatment of erectile
      dysfunction (ED). METHODS: A total of 586 male patients with ED in association
      with and without PE or low desire were enrolled in this study. Patients were
      screened for ED using the International Index for Erectile Function. All patients
      were also screened for PE and low desire. We compared the responses to the
      erectile function domain, questions 3 and 4, before and after sildenafil in
      patients with and without PE or low desire. Overall satisfaction and global
      efficacy question responses were also assessed in all patients. RESULTS: The mean
      age +/- SD was 58 +/- 6.4 years. Significant associations were found between the
      increased duration and severity of ED and the decreased rate of overall
      satisfaction. Before sildenafil administration, significant differences were
      found in the erectile function domain, Q3 and Q4 between patients with and
      without PE or low desire. After sildenafil administration, no significant
      differences were found in those assessment variables and the presence or absence
      of PE and low desire. No significant differences were found between the global
      efficacy question response and the overall satisfaction rate between patients
      with and without PE or low desire. CONCLUSIONS: The efficacy of sildenafil was
      negatively affected by an increased duration and severity of ED; however, global
      efficacy and overall patient satisfaction were not attenuated by PE or low
      desire.

PMID- 16979719
TI  - Outcomes of Gleason score 10 prostate carcinoma treated by radical prostatectomy.
AB  - OBJECTIVES: To evaluate the outcome of radical prostatectomy for the rarest and
      most poorly differentiated prostate tumors of all: those with Gleason score 10.
      Controversy exists as to which form of therapy is most effective for high-grade
      prostate cancer (PCa). METHODS: We retrospectively reviewed the charts of all
      patients with pathologic Gleason score 10 PCa treated at our institution with
      radical prostatectomy from 1977 to 1999. All pathology specimens were reviewed by
      a urologic pathologist, and 13 cases with true Gleason score 10 PCa were
      identified. The preoperative covariables (prostate-specific antigen level, biopsy
      Gleason score, and clinical stage), perioperative covariables (pathologic stage,
      margin status, and tumor ploidy), and postoperative covariables (prostate
      specific antigen level and adjuvant and salvage treatments) were assessed with
      respect to the oncologic outcomes. RESULTS: The median follow-up was 4.2 years.
      Preoperatively, only 4 of the 13 cases were correctly identified at biopsy, and
      the median preoperative prostate-specific antigen level was 4.5 ng/mL
      (interquartile range 0.3 to 12.5). Pathologic examination showed a small cell
      component in 7 cases, seminal vesicle invasion in 11, and positive lymph nodes in
      3. Six patients developed recurrent PCa: three local, two systemic, and one
      biochemical recurrence. The biochemical recurrence-free and cancer-specific
      survival rate at 5 years was 53.8% and 76.9%, respectively. CONCLUSIONS: Gleason
      score 10 PCa is a highly aggressive disease that is usually lethal if managed
      conservatively. The results of the present study have provided some evidence that
      radical prostatectomy may be of benefit to patients with Gleason score 10 PCa.

PMID- 16979720
TI  - Should function and bother be measured and reported separately for prostate
      cancer quality-of-life domains?
AB  - OBJECTIVES: To evaluate the psychometric properties of the three domains bowel,
      urinary, and sexual function as they were measured in the Prostate Cancer
      Outcomes Study and examine their use in different research and practice settings.
      Leading prostate cancer health-related quality-of-life questionnaires include
      questions that measure patients' bowel, urinary, and sexual function and their
      perceived annoyance (or bother) caused by limited functioning. The published
      results are mixed on reporting function and bother independently or together as a
      single domain. METHODS: Statistical tools from classical measurement theory and
      factor analytic methods were used to evaluate the psychometric properties of the
      Prostate Cancer Outcomes Study disease-specific scales. The findings from studies
      of other prostate cancer outcomes scales and clinical input were included to
      formulate the conclusions. RESULTS: Factor analysis results uncovered a
      multidimensional structure within two of the three domains. The urinary domain
      consisted of items measuring two factors: incontinence and urinary obstructive
      symptoms. Sexual dysfunction consisted of two dimensions: interest in sexual
      activity and erectile function. CONCLUSIONS: These empirical results suggest that
      bowel dysfunction and urinary incontinence can each be combined with measures of
      bother to produce overall measures of function; however, evidence was present for
      the need for separate measures of sexual function, sexual interest, and perceived
      bother with sexual function. For informing patient-doctor communications,
      function and bother on all three domains should be reported separately, because
      treatment decisions or symptom management may vary depending on a patient's
      perceived concern about their health-related quality-of-life.

PMID- 16979721
TI  - Testicular microlithiasis identified ultrasonographically in Japanese adult
      patients: prevalence and associated conditions.
AB  - OBJECTIVES: To determine the prevalence of testicular microlithiasis (TM) seen by
      testicular ultrasonography (US) in Japanese adult men referred for andrologic
      symptoms and evaluate associations of TM with pathologic conditions. METHODS: For
      7 years, US was performed in 969 patients (mean age 40.9 years) at one
      institution. The patients were divided into groups with infertility (n = 550),
      unilateral testicular tumor (n = 46), or other andrologic conditions (n = 373).
      TM was identified as multiple small hyperechogenic foci. In the tumor group, only
      images of the tumor-free testis were reviewed. Patients with TM accompanying
      tumor or infertility completed follow-up questionnaires and US examinations.
      RESULTS: TM was diagnosed in 46 patients (mean age 38.5 years, range 23 to 75).
      The prevalence of TM was 17.4% in the tumor group, 5.6% in the infertility group,
      and 1.9% in the other-conditions group. TM was associated with testicular tumor
      and infertility, but not with other conditions. In patients with unilateral
      testicular germ cell tumor, the prevalence of carcinoma in situ in the
      contralateral testis was greater when TM was present in that testis (2 of 8
      patients) than when TM was absent (0 of 32, P = 0.0037). No new testicular tumor
      developed subsequently. In the infertility group, the 31 patients with TM showed
      no subsequent testicular tumor development, and neither patient undergoing
      testicular biopsy had carcinoma in situ. CONCLUSIONS: TM, as demonstrated by US,
      was associated with infertility, as well as testicular tumor. TM in a testis
      contralateral to a unilateral testicular germ cell tumor may increase the risk of
      carcinoma in situ.

PMID- 16979722
TI  - Impact of Parkinson's disease on continence after radical prostatectomy.
AB  - OBJECTIVES: It is widely believed that men with idiopathic Parkinson's disease
      (PD) should not undergo prostate surgery because of the prohibitively high risk
      of incontinence. However, the data supporting this conclusion were based on
      cohorts undergoing prostate surgery for voiding dysfunction, not for cancer
      control. Because both prostate cancer and PD are predominantly diseases of the
      elderly, it is likely that some men are concurrently diagnosed with both
      disorders who would otherwise be good candidates for radical prostatectomy (RP).
      However, the urinary outcomes in men with PD undergoing RP are unknown. Thus, it
      is possible that men with PD have been denied a potentially curative surgery only
      on the basis of long-standing assumptions. We addressed this issue by examining a
      cohort of men with PD who underwent RP at our institution. METHODS: We
      retrospectively reviewed a cohort of men who had undergone RP at our institution
      from 1990 to 2000. These men were surveyed 1 year after their surgery to
      determine their continence status, and their records were reviewed to determine
      whether any men had been preoperatively diagnosed with PD. RESULTS: Of the 8415
      men undergoing RP during the study period, 20 had PD and were included in our
      study. Their de novo incontinence rate at 1 year was 24%, with no patient
      requiring more than one to two pads per day. CONCLUSIONS: Most men with PD
      undergoing RP remained continent 1 year after surgery. Additional studies with
      longer follow-up are required to determine whether this remains true over time.

PMID- 16979723
TI  - Removal of more lymph nodes may provide better outcome, as well as more accurate
      pathologic findings, in patients with bladder cancer--analysis of role of pelvic
      lymph node dissection.
AB  - OBJECTIVES: To examine the role of pelvic lymph node dissection (PLND) in
      patients who underwent radical cystectomy for bladder cancer. The diagnostic and
      therapeutic role of PLND is still controversial in bladder cancer. The extent of
      PLND and the necessary number of lymph nodes to remove have not been defined.
      METHODS: This retrospective review included 146 patients with refractory
      superficial and muscle-invasive disease treated with radical cystectomy, regional
      PLND (internal iliac, external iliac, and obturator nodes) and urinary diversion
      from January 1990 to December 2002. RESULTS: Lymph node metastases were detected
      in 25 patients (17.1%). The average number of nodes removed in the node-positive
      and node-negative patients was 13.9 and 14.2, respectively. Although no
      difference was found in disease-specific survival in the node-negative patients
      when stratified by the number of nodes removed (13 or more versus less than 13),
      a significant survival advantage was found in the node-positive patients with 13
      or more nodes removed versus less than 13 nodes removed. The patients with four
      or more positive nodes had a worse outcome than those with less than four
      positive nodes. However, even if the patients had less than four positive nodes,
      the survival of patients with less than 13 nodes removed was as poor as that of
      the patients with four or more positive nodes. CONCLUSIONS: In this series, the
      removal of 13 or more pelvic lymph nodes was essential for more accurate
      pathologic examination to predict patient outcome and contributed to an increased
      chance of survival.

PMID- 16979724
TI  - Complications and troubleshooting of two-stage sacral neuromodulation therapy: a
      single-institution experience.
AB  - OBJECTIVES: With the increasing use of sacral neuromodulation therapy, urologists
      are faced with postimplantation challenges. The purpose of this study was to
      identify these events and their causes and management in our large single
      institution experience. METHODS: From July 2002 to September 2004, all patients
      who underwent sacral neuromodulation therapy for refractory bladder conditions
      were identified. Their medical records were retrospectively evaluated for
      history, operative intervention, and programming visits. Events after
      implantation of the implantable pulse generator (IPG) unit were noted. The
      evaluation, troubleshooting, management, and resolution of events at the last
      follow-up visit were extracted. RESULTS: A total of 214 patients underwent sacral
      neuromodulation therapy at our institution. The mean patient age was 53.5 +/-
      15.4 years. Of the 214 patients, 161 underwent IPG implantation during a mean
      follow-up period of 16 months (range 5 to 30). The second-stage explantation and
      revision rate was 10.5% and 16.1%, respectively. The indications for explantation
      were infection (8 of 17) and failure to maintain a response (9 of 17). Revisions
      were done for decreases in response with abnormal (12 of 26) or normal (5 of 26)
      impedance measurements, IPG site discomfort (4 of 26), draining sinus at the IPG
      site (4 of 26), and lead migration (1 of 26). Equalization of impedance
      measurements was the most commonly observed impedance abnormality. These were
      managed by drying fluid from the connection in 4 patients and lead change in the
      rest. CONCLUSIONS: After IPG implantation, a decline in response may occur.
      Although some were explanted, most were revised, with most of the revisions
      functional on follow-up. Familiarity with impedance evaluation and development of
      algorithms for postimplant management are essential for troubleshooting and
      maintenance of the device.

PMID- 16979725
TI  - Multiple metachronous brain metastases from primary ureteral carcinoma.
AB  - Transitional cell carcinoma (TCC) of the ureter is an uncommon urologic
      malignancy, with approximately 150 cases diagnosed annually. Metastatic brain
      disease from ureteral TCC is exceedingly rare. To our knowledge, our case report
      represents only the second report of brain metastasis from ureteral TCC and the
      only reported patient to undergo resection of their TCC brain metastasis.

PMID- 16979726
TI  - Epidemiologic survey of lower urinary tract symptoms in Japan.
AB  - OBJECTIVES: A large-scale nationwide epidemiologic survey was performed to
      determine the prevalence of lower urinary tract symptoms (LUTS) and their impact
      on health-related quality of life (HRQOL) in Japan. METHODS: A self-administered
      questionnaire was mailed to 10,096 randomly selected Japanese men and women aged
      40 years or older. The survey questions, developed by the Japan Neurogenic
      Bladder Society, encompassed four areas: demographic characteristics, LUTS,
      HRQOL, and treatment seeking. A modified King's Health Questionnaire was used to
      evaluate HRQOL. Correlations among the response scores were analyzed by
      Spearman's rank test. RESULTS: The responses from 4570 subjects (mean age 61
      years) were analyzed. The prevalence rate for daytime urinary frequency of 8 and
      11 times or more daily was 50% and 11%, respectively. The prevalence of nocturia
      occurring 1 and 3 or more times/night was 69% and 14%, respectively. For other
      symptom frequency (ie, weak urine flow, sensation of residual urine, bladder
      pain, urinary urgency, urgency incontinence, stress incontinence, and
      incontinence pad use), the prevalence rates ranged from 2% to 27% for 1 or more
      times/wk and 1% to 20% for 1 or more times/day. Emotions and sleep/energy were
      most affected by LUTS (10% each), followed by physical limitations (7%), role
      limitations (6%), social limitations (4%), and personal relationships (3%).
      Nocturia was most frequently (38%) reported to have the greatest impact on HRQOL.
      Of those who considered their daily life to be affected by LUTS, only 18% sought
      medical care. CONCLUSIONS: Although LUTS are highly prevalent in Japan, few
      subjects seek treatment. Greater awareness and understanding of LUTS is needed to
      manage symptoms and their consequences appropriately.

PMID- 16979727
TI  - Biologic significance of fascin expression in clear cell renal cell carcinoma:
      systematic analysis of primary and metastatic tumor tissues using a tissue
      microarray technique.
AB  - OBJECTIVES: To investigate the biologic significance of fascin, a globular actin
      cross-linking protein, involved in cell adhesion and motility, in primary and
      metastatic renal cell carcinoma (RCC). METHODS: A total of 136 primary clear cell
      RCCs and 54 clear cell RCC metastases were stained immunohistochemically using a
      tissue microarray technique. Distinct cytoplasmic staining was considered
      positive, and the staining results were associated with the pT stage, Fuhrman
      grade, tumor size, sarcomatoid morphology, and metastasis-free survival. For
      multivariate testing, Cox's proportional hazards regression model was used.
      RESULTS: Fascin expression was noted in 13 (10%) of 136 primary and 25 (46%) of
      54 metastatic RCC specimens (P <0.001). Fascin expression was associated with
      high tumor stage (2 [3%] of 70 pT1 versus 11 [17%] of pT2/pT3; P = 0.008), high
      tumor grade (3 [3%] of 88 grade 1-2 versus 10 [21%] of 48 grade 3-4; P = 0.002),
      and large tumor size (P <0.001). In addition, 8 (62%) of 13 RCCs with sarcomatoid
      morphology expressed fascin compared with 5 (4%) of 123 RCCs without sarcomatoid
      transformation (P <0.001). Metastatic disease was noted in 10 (77%) of 13
      patients with fascin-positive RCC compared with 26 (21%) of 121 patients with
      fascin-negative RCC (P <0.001). Multivariate analysis revealed pT Stage 1 or
      greater (P <0.001, risk ratio [RR] 8.6, 95% confidence interval [CI] 2.8 to
      26.5), Fuhrman grade greater than 2 (P <0.001, RR 12.7, 95% CI 4.6 to 35.4),
      fascin expression (P <0.001, RR 7.2, 95% CI 3.0 to 17.4), and female gender (P =
      0.02, RR 2.5, 95% CI 1.1 to 5.5) as independent predictors of metastatic disease.
      CONCLUSIONS: Fascin immunoreactivity in RCC proved to be an independent predictor
      of metastatic disease and was demonstrated in almost one half of RCC metastases.
      Thus, fascin may be a promising molecular target for future cancer therapy.

PMID- 16979728
TI  - Laparoscopic radical prostatectomy in a renal allograft recipient.
AB  - In the current immunosuppression era, most renal transplant recipients with a
      functioning allograft are living healthier and longer lives. In men, because of
      prostate-specific antigen screening, more patients are diagnosed with early
      prostate cancer and offered curative treatment with radical prostatectomy.
      Laparoscopic radical prostatectomy is an accepted minimally invasive treatment
      for a middle-aged man with organ-confined prostate cancer. To our knowledge,
      laparoscopic prostatectomy has not yet been reported in renal transplant
      recipients. This is a case report of laparoscopic prostatectomy for biopsy-proven
      localized prostate cancer in a renal transplant recipient.

PMID- 16979729
TI  - Oncolytic viral therapy by bladder instillation using an E1A, E1B double
      restricted adenovirus in an orthotopic bladder cancer model.
AB  - OBJECTIVES: To investigate the therapeutic effect of AxdAdB-3, a double
      restricted oncolytic adenovirus harboring a mutant E1A and an E1B-55KD deletion,
      on human bladder cancer cell lines and the SCID mouse model of orthotopic bladder
      cancer. METHODS: The cytopathic effects of AxdAdB-3 were evaluated in several
      cell lines (YTS-1, YTS-3, T24, J82, 5637) derived from human bladder or ureteral
      cancer and in a normal bladder mucosa-derived cell line (HCV29) with AxCAlacZ
      (control) or AxE1AdB (E1B-55KD-defective adenovirus) or dl922-947 (E1A-mutated
      adenovirus). The efficacy of bladder instillation therapy with AxdAdB-3 for
      orthotopic bladder cancer of SCID mice was investigated. The oncolytic effects
      were monitored by ultrasound examination. RESULTS: AxdAdB-3 caused the oncolysis
      of bladder cancer cell lines in vitro, and it was more cytopathic than AxE1AdB or
      dl922-947 in the cancer cell lines. AxdAdB-3 was not cytotoxic against HCV29.
      Direct instillation of AxdAdB-3 into the bladder of the orthotopic model
      inhibited tumor growth, leading to significantly prolonged survival. CONCLUSIONS:
      Oncolytic viral therapy delivered by instillation of AxdAdB-3 is a promising tool
      for treating bladder cancer.

PMID- 16979730
TI  - Impact of patient age on distal hypospadias repair: a surgical perspective.
AB  - OBJECTIVES: To assess whether the age at which the initial hypospadias repair is
      performed influences the complication rate of hypospadias repair. METHODS: The
      records of 325 consecutive patients who underwent initial hypospadias repair were
      reviewed. The patients with glanular and coronal hypospadias underwent repair
      with either meatoplasty and glanuloplasty or a glans approximation procedure.
      Patients with subcoronal hypospadias and penile hypospadias underwent repair with
      tubularized incised plate urethroplasty. The patients were divided into 6-month
      age groups, and the complication rates were analyzed by age group using the chi
      square test. RESULTS: A total of 325 hypospadias repairs were performed from
      January 1999 to January 2005 by a single surgeon. Of the 325 cases, 194
      tubularized incised plate procedures were performed, 69 meatoplasty and
      glanuloplasty procedures were performed, and 53 glans approximation procedures
      were performed. Nine tubularized island flap urethroplasties performed for
      penoscrotal hypospadias were excluded because we did not perform a significant
      number of proximal urethroplasties. Nineteen patients (6.0%) developed
      urethrocutaneous fistulas and six (1.9%) demonstrated dehiscence. Overall, 2
      patients (2.2%) who underwent surgical repair within the first 6 months of age
      developed complications compared with 23 patients (10.3%) who underwent initial
      hypospadias repair when they were older than 6 months of age (P = 0.006).
      CONCLUSIONS: Tubularized incised plate, meatoplasty and glanuloplasty, and glans
      approximation urethroplasty are all excellent options for the surgical correction
      of hypospadias in the appropriately selected patient. The results of our study
      have indicated that complications are minimized when hypospadias repair is
      performed when the patient is 4 to 6 months of age.

PMID- 16979731
TI  - Use of different definitions of biochemical failure after external beam
      radiotherapy changes conclusions about relative treatment efficacy for localized
      prostate cancer.
AB  - OBJECTIVES: To report biochemical relapse-free survival (bRFS) after radiotherapy
      (RT) for localized prostate cancer with two separate failure definitions and
      compare the results with those after radical prostatectomy (RP). METHODS: The
      study sample comprised 2516 patients with a median follow-up of 78 months.
      Biochemical relapse after RT was defined as either the American Society for
      Therapeutic Radiology Oncology definition (definition A [DefA]) or a prostate
      specific antigen elevation of more than 2 ng/mL greater than the nadir prostate
      specific antigen level (definition N [DefN]). Failure after RP was defined as a
      prostate-specific antigen level greater than 0.2 ng/mL. RESULTS: Compared with
      DefA, DefN resulted in a 13% greater bRFS rate at 5 years and a 12% lower bRFS
      rate at 10 years. On multivariate analysis, the treatment modality (RP versus RT)
      was a significant predictor of bRFS using DefA in favor of RP (P <0.001), but was
      not with DefN (P = 0.87). Higher radiation doses were independently associated
      with a better outcome with either definition. CONCLUSIONS: Compared with DefA,
      DefN resulted in better outcomes for up to 7 years after RT, but worse outcomes
      thereafter. The use of DefA versus DefN resulted in opposite conclusions about
      the relative efficacies of RT and RP, with DefN suggesting RT is equivalent to RP
      and DefA that it is worse than RP. Different definitions of biochemical failure
      after RT can result in differences in the conclusions about treatment efficacy in
      men with localized prostate cancer, thereby potentially affecting clinical
      decisions.

PMID- 16979732
TI  - Ultrasound imaging of sacral reflexes.
AB  - OBJECTIVES: To investigate the reliability of examination of the guarding reflex
      of the pelvic floor by dynamic perineal ultrasonography in children with bladder
      dysfunction and in controls. METHODS: A total of 40 patients with nonneurogenic
      bladder/sphincter dyssynergia, 40 with spina bifida, and 40 controls underwent a
      dynamic ultrasound examination of the pelvic floor while coughing and while being
      tapped on the abdominal wall. The reflex action of the puborectal muscle in
      females, and the combined action of the puborectal muscle and external sphincter
      muscle in males, were recorded. RESULTS: Of the 40 patients with nonneurogenic
      bladder/sphincter dyssynergia, 38 had a normal reflex action of the puborectal
      muscle during the abdominal tap and 36 had a normal reflex action when coughing.
      Two of these patients had unexplained underactive bladder syndrome and were using
      clean intermittent catheterization, and two could not be assessed because of
      hypermobility of the bladder neck when coughing but had a normal reaction during
      abdominal tapping. Of the 40 patients with spina bifida, none had puborectal
      activity during coughing and 5 had some puborectal activity during tapping. Of
      the 40 controls, 39 had normal reflex activity during both coughing and tapping.
      CONCLUSIONS: The question of whether a child has nonneurogenic or neuropathic
      bladder/sphincter dysfunction is often difficult to answer on the basis of
      urodynamic studies alone. Dynamic perineal ultrasound recording of the S2-S4
      reflex arches provides reliable additional information and is noninvasive to the
      patient.

PMID- 16979733
TI  - Risk stratification in penile carcinoma: 25-year experience with surgical
      inguinal lymph node staging.
AB  - OBJECTIVES: In penile carcinoma, the most reliable staging method for lymph node
      involvement remains radical dissection with its associated high morbidity.
      However, the patient's prognosis is closely associated with lymph node status,
      and radical dissection is potentially curative. We report our experience with
      surgical lymph node staging and evaluate which group of patients could be
      assigned to a wait-and-see strategy or dynamic sentinel node biopsy and which
      group should undergo groin dissection. METHODS: From 1979 to 2004, 56 consecutive
      patients with penile cancer underwent surgical inguinal lymph node staging. On
      the basis of the histopathologic results, we defined risk stratification into
      low, high, and intermediate-risk groups according to the clinical examination
      findings, stage, and grade. RESULTS: Tumor stage (P = 0.019) and tumor grade (P
      <0.001) correlated significantly with lymph node status. Stratification into low
      (pT1G1, pT1G2), high (all G3 tumors), and intermediate-risk (all others) groups
      found 7.7% of low-risk patients with metastases. In the intermediate and high
      risk groups, 28.6% and 75.0% had nodal metastases, respectively. Correlation with
      nodal involvement according to risk group was R2 = 0.608 (P <0.001). CONCLUSIONS:
      Risk stratification might enable a modified staging strategy for lymph node
      status according to stage, grade, and clinical examination findings. Highly
      motivated low-risk patients could be included in a surveillance program; however,
      high-risk patients should undergo bilateral inguinal dissection. Dynamic sentinel
      lymph node biopsy might be encouraged for intermediate-risk patients in the
      future.

PMID- 16979734
TI  - Closing the tract of mini-percutaneous nephrolithotomy with gelatine matrix
      hemostatic sealant can replace nephrostomy tube placement.
AB  - OBJECTIVES: To investigate the outcomes using gelatine matrix hemostatic sealant
      to close the tract after mini-percutaneous nephrolithotomy (mini-PCNL), resulting
      in a tubeless setting. METHODS: After complete stone removal after mini-PCNL, a
      double-J ureteral stent was placed in an antegrade manner. After withdrawing the
      17F Amplatz sheet from the collecting system under direct vision without
      irrigation, the urothelium collapsed. While retracting the sheet further, the
      gelatine matrix hemostatic sealant was injected. The skin incision was closed
      with glue. An ultrasound examination was performed on the first postoperative day
      to exclude the presence of urine extravasation. RESULTS: Mini-PCNL was performed
      in 11 patients, either as a primary, small stone, single-access procedure or as a
      second-look mini-PCNL because of small residual fragments after extracorporeal
      shock wave lithotripsy. The time to seal the mini-PCNL tract through the kidney
      parenchyma was 2 to 5 minutes. The mean operative time was 79 minutes. In the
      first 5 cases, intravenous urography was performed in addition to ultrasonography
      and demonstrated an intact collecting system. The subsequent procedures
      demonstrated similar findings, with the exception of 1 case of temporary
      paravasation. In all other patients, the catheter was removed on the first
      postoperative day. Ten of 11 patients had an uneventful follow-up until removal
      of the double-J catheter. No major complications were observed. CONCLUSIONS:
      Closing the tract of the mini-PCNL with gelatine matrix hemostatic sealant is a
      safe and fast alternative and provides the option of discharging the patient in
      good condition without the commonly used nephrostomy tube.

PMID- 16979735
TI  - Clinical model of lifetime cost of treating bladder cancer and associated
      complications.
AB  - OBJECTIVES: To estimate the lifetime cost of bladder cancer and the contribution
      of complications to the total costs. METHODS: We reviewed the medical records of
      a retrospective cohort of 208 patients with bladder cancer who registered at our
      comprehensive cancer center from 1991 to 1999. We multiplied the number of
      resources used during management of bladder cancer by their unit charges. We
      converted charges into costs using the Medicare cost-to-charge ratio and inflated
      these to 2005 U.S. dollars. We estimated future costs by creating two extreme
      hypothetical scenarios. In the best-case scenario, we assumed patients with
      superficial disease developed recurrences at the cohort's mean rate and that
      patients with muscle-invasive disease were disease free after definitive therapy.
      Survival was based on the U.S. life expectancy in both cases. In the worst-case
      scenario, we assumed patients with superficial disease developed muscle-invasive
      disease and that all patients subsequently died of bladder cancer. RESULTS: The
      average cost of bladder cancer was 65,158 dollars among the cohort patients.
      Sixty percent of this cost (39,393 dollars) was associated with surveillance and
      treatment of recurrences, and 30% (19,811 dollars) was attributable to
      complications. The lifetime cost of bladder cancer was lower for the worst-case
      scenario (99,270 dollars) than for the best-case scenario (120,684 dollars).
      However, a greater proportion of the costs were attributable to complications
      with the worst-case scenario (43%, 42,290 dollars) compared with the best (28%,
      34,169 dollars). CONCLUSIONS: The management of bladder cancer and its associated
      complications results in a major economic burden. More cost-effective
      surveillance strategies and approaches for preventing complications are crucial
      to minimizing the disease's clinical and economic consequences.

PMID- 16979736
TI  - Minimizing knot tying during reconstructive laparoscopic urology.
AB  - OBJECTIVES: Intracorporeal knot tying during urologic reconstructive surgery is
      one of the most technically challenging skills of laparoscopic surgery. We
      describe our experience using the Lapra-Ty clip to substitute for knot tying.
      METHODS: Our technique for minimizing knot tying entails the use of the Lapra-Ty
      clip during closure of the collecting system and renal parenchyma for
      laparoscopic partial nephrectomy, the vesicourethral anastomosis during robotic
      laparoscopic radical prostatectomy, and the collecting system during laparoscopic
      pyeloplasty. From October 2002 to July 2005 at our institution, 75 patients
      underwent laparoscopic partial nephrectomy, 300 underwent robotic laparoscopic
      radical prostatectomy, and 14 underwent laparoscopic pyeloplasty. We reviewed the
      charts retrospectively for intraoperative and postoperative parameters related to
      the use of these clips. RESULTS: In the laparoscopic partial nephrectomy group,
      the mean tumor size, warm ischemia time, and estimated blood loss was 2.53 cm,
      30.1 minutes, and 189 mL, respectively. Two postoperative urine leaks (2.7%)
      developed, and 3 patients experienced postoperative bleeding (4%). In the robotic
      laparoscopic radical prostatectomy group, the mean operative time was 295 minutes
      and the mean estimated blood loss was 303.6 mL. Only 3 patients had a urine leak
      (1%), and 4 patients had bladder neck contracture (1.3%). With regard to the
      laparoscopic pyeloplasty group, the mean operative time and estimated blood loss
      was 224 minutes and 36 mL, respectively. No intraoperative complications or
      urinary leaks occurred. CONCLUSIONS: Using the Lapra-Ty clip, we have safely and
      efficiently supplemented knot tying in patients undergoing reconstructive
      laparoscopic surgery.

PMID- 16979737
TI  - Radical cystectomy with ultrasound-guided partial prostatectomy for bladder
      cancer: a complication-preventing concept.
AB  - OBJECTIVES: Radical cystectomy has been the reference standard for the treatment
      of muscle-invasive bladder cancer. However, this kind of therapy does have an
      impact on the patient's quality of life. For this reason, we performed prostate
      sparing surgery during radical cystectomy without compromising the oncologic
      outcome. METHODS: From December 2003 to August 2005, 31 patients with a mean age
      of 63.6 +/- 8 years (range 48 to 79) underwent apex-sparing radical
      cystoprostatectomy for invasive bladder cancer. All patients underwent
      transurethral biopsy in the prostatic urethra to exclude urothelial tumor and
      transrectal ultrasound-guided biopsy of the prostate to diagnose concomitant
      prostate cancer. Patients with a prostate-specific antigen level greater than 4
      ng/mL were excluded from prostate-sparing cystectomy. The mean follow-up period
      was 12 months. RESULTS: The postoperative pathologic stage was pTis in 2
      patients, pTa in 1, pT1 in 3, pT2 in 20, pT3 in 5, and pN+ in 4 patients. We
      found no prostate cancer on histopathologic evaluation. Except for 4 patients, no
      patient had deterioration of sexual function. Except for 2 patients, all patients
      were fully continent. CONCLUSIONS: Radical cystectomy with prostate-sparing
      surgery in patients with invasive bladder cancer resulted in improved continence
      and improved erectile function. Additionally, with apex-sparing radical
      cystoprostatectomy, we were able to create a wide neovesicourethral anastomosis
      to prevent strictures, urinary retention, and mucous retention. It is absolutely
      necessary that this procedure be restricted to highly selected patients.

PMID- 16979738
TI  - Laparoscopic management of advanced renal cell carcinoma with level I renal vein
      thrombus.
AB  - OBJECTIVES: To present our series of laparoscopic radical nephrectomy in patients
      with level I tumor thrombus. The existence of renal vein tumor thrombus presents
      a technical challenge in securing hilar control during the resection of a renal
      mass. To our knowledge, this experience represents one of the largest series of
      laparoscopic nephrectomy for renal cell carcinoma associated with a macroscopic
      renal vein thrombus. METHODS: From April 2002 to June 2004, 12 patients (8 men
      and 4 women) were diagnosed with renal masses. In addition to computed
      tomography, cavography and magnetic resonance imaging were used to determine the
      levels of tumor thrombi preoperatively in those who had suspicious involvement of
      the renal vein on computed tomography. RESULTS: Laparoscopic nephrectomy was
      performed in a standard fashion. Hand-assisted laparoscopic nephrectomy was used
      in 6 cases involving large tumors with bulky hilar adenopathy. All renal veins
      were stapled using an endoscopic vascular stapler. Intraoperative laparoscopic
      ultrasonography was used to delineate the extent of the vein thrombus in 4 cases
      to enable proper stapler positioning. No intraoperative complications occurred,
      and 2 cases were electively converted to open nephrectomy. The postoperative
      narcotic requirements and hospitalization times were low. Pathologic examination
      of the tumor specimens demonstrated negative resection margins in all patients.
      CONCLUSIONS: In carefully selected patients, laparoscopic resection of renal
      masses with level I renal vein thrombi is feasible. Because of technical
      considerations that may be identified intraoperatively, early conversion to open
      nephrectomy should be anticipated. Long-term results regarding oncologic control
      continue to be assessed.

PMID- 16979739
TI  - Bilateral testicular masses: an unusual presentation of neuroblastoma.
AB  - We describe a rare occurrence of an 11-month-old male infant with metastatic
      bilateral testicular neuroblastoma presenting with bilateral scrotal swelling.

PMID- 16979740
TI  - Comorbidity is poor predictor of survival in patients undergoing radical
      prostatectomy after 70 years of age.
AB  - OBJECTIVES: To investigate several comorbidity classifications as possible
      predictors of mortality, because the value of comorbidity as a prognostic factor
      is uncertain in patients older than 70 years of age and radical prostatectomy in
      patients older than 70 years is controversial. METHODS: A total of 214
      consecutive patients aged 70 years or older who underwent radical prostatectomy
      from December 1992 to December 2002 were stratified according to the Charlson
      score, American Society of Anesthesiologists physical status classification, New
      York Heart Association classification of cardiac insufficiency, classification of
      angina pectoris from the Canadian Cardiovascular Society, and age (70 to 72
      versus 73 to 74 versus 75 years or older). The mean follow-up in the surviving
      patients was 5.1 years (range 1.3 to 12.5). A sample of 240 consecutive patients
      aged 67.0 to 69.9 years treated during the same period was used for comparison.
      The overall and comorbid mortality were the study endpoints. Mantel-Haenszel
      hazard ratios were calculated. Comparisons were made using the log-rank test.
      RESULTS: Unlike for patients aged 67.0 to 69.9 years, for those 70 years old or
      older, only one of the investigated stratifications reached significance as a
      predictor of mortality. A New York Heart Association classification of 2+ versus
      0 was significant for overall mortality (hazard ratio 5.8, P = 0.021) and
      comorbid mortality (hazard ratio 15.9, P = 0.046). CONCLUSIONS: Comorbidity is of
      limited prognostic value in patients selected for radical prostatectomy and 70
      years old or older.

PMID- 16979741
TI  - Cavernous hemangioma of tunica albuginea testis manifesting as testicular pain.
AB  - Cavernous hemangioma of the tunica albuginea of the testis is very rare; only 2
      cases have been reported in published studies. Both cases presented as testicular
      masses. We report what we believe to be the third case of cavernous hemangioma of
      the tunica albuginea that manifested as pain without any mass.

PMID- 16979742
TI  - A contemporary look at Dr. Hugh Hampton Young.

PMID- 16979743
TI  - Relationship between serum prostate-specific antigen levels and body mass index
      in healthy younger men.
AB  - OBJECTIVES: To understand further the physiologic characteristics of serum
      prostate-specific antigen (PSA) concentrations in healthy younger men. METHODS: A
      total of 2032 men, 20 to 39 years old, who visited our hospital for a routine
      health checkup were entered into the study. Pearson correlation coefficients were
      determined to evaluate the association between serum PSA and clinical parameters.
      Because of the log-normal distribution, the serum PSA levels were log-transformed
      for analysis. RESULTS: Although the relationships were weak, significant negative
      correlations were noted between serum PSA and body weight (r = -0.107, P <0.001),
      body mass index (BMI; r = -0.131, P <0.001), aspartate aminotransferase (AST; r =
      -0.076, P = 0.001), alanine aminotransferase (ALT; r = -0.079, P = 0.001), gamma
      glutamyltransferase (r = -0.046, P = 0.046), and creatinine clearance (r = 
      0.113, P <0.001). A positive correlation was found between serum PSA and
      creatinine (r = 0.053, P = 0.024). Age did not correlate with serum PSA level.
      The influence of clinical parameters on serum PSA was explored using multiple
      linear regression analysis. Using the stepwise method, all other explanatory
      variables, except BMI, AST, and creatinine were eliminated (log10[PSA] = 
      0.124[BMI] + 0.063[creatinine] - 0.053[AST] + 0.097; r = 0.152, P <0.001).
      CONCLUSIONS: BMI, creatinine, and AST may influence the serum PSA level in this
      population. However, because it was not clear that this group should be
      considered at high risk of prostate cancer in the future, additional longitudinal
      research is needed.

PMID- 16979744
TI  - Inactivation of myopodin expression associated with prostate cancer relapse.
AB  - OBJECTIVES: Myopodin has recently been characterized as a tumor suppressor gene
      whose encoded product inhibits prostate cancer growth and metastasis both in
      vitro and in animal models. However, the clinical evidence of tumor suppression
      in humans is still lacking. In this study, we conducted a large-scale analysis of
      myopodin expression in prostate cancer samples to examine the relationship
      between myopodin expression and prostate cancer grade and stage and the
      probability of clinical relapse. METHODS: Immunostaining using anti-myopodin
      antibodies was performed on 746 formalin-fixed paraffin-embedded tissue samples
      to evaluate the level of myopodin expression in normal and malignant prostatic
      tissue. RESULTS: The expression of myopodin was semiquantitatively determined by
      immunostaining. The myopodin expression levels were examined in relation to
      prostate cancer grade and stage, preoperative prostate-specific antigen level,
      surgical margin involvement, tumor volume, and clinical relapse. The mean
      myopodin expression score (range 0 to 3) was 2.1 and 0.88 for benign prostatic
      tissue and prostate cancer, respectively. Minimal variation in myopodin
      expression was observed among the various grades, stages, tumor volumes, and
      preoperative prostate-specific antigen levels of prostate cancer. However,
      samples with positive surgical margins were associated with lower myopodin
      expression. Complete inactivation of myopodin expression correlated with a
      greater than 86% rate of clinical relapse. CONCLUSIONS: Our results suggest that
      myopodin is an important predictor of prostate cancer metastasis, independent of
      Gleason score, preoperative prostate-specific antigen level, and tumor stage.

PMID- 16979745
TI  - Percutaneous treatment of large upper tract stones after urinary diversion.
AB  - OBJECTIVES: To present our experience in percutaneous management of large upper
      tract stones after urinary diversion. METHODS: From October 1984 to March 2005,
      20 percutaneous nephrolithotomy and 4 antegrade ureteroscopy procedures were
      performed in 17 men and 7 women, with a mean age of 53.5 years. The urinary
      diversions were an ileal W neobladder, hemi-Kock pouch, ileal conduit, and rectal
      bladder in 10, 7, 4, and 3 patients, respectively. The median interval between
      diversion and stone management was 1.5 years. Success was defined as a stone
      free, nonobstructed renal unit at 3 months after the intervention. Follow-up was
      performed every 6 months with intravenous urography or noncontrast computed
      tomography for diagnosis of stone recurrence and evaluation of renal morphology.
      RESULTS: Renal punctures were guided with ultrasonography in 18 patients (75%)
      and fluoroscopy in 6 patients. One intraoperative complication (4.16%) and two
      postoperative complications (8.3%) occurred. All patients with ureteral stones
      became stone free after one procedure. Auxiliary procedures were needed in 5
      patients after percutaneous nephrolithotomy; 2 patients required a second session
      and 3 needed extracorporeal shock wave lithotripsy. The overall success rate was
      87.5% (21 patients). One patient with treatment failure underwent open surgery,
      and two with small residual fragments were followed up. Long-term follow-up data
      were available for 15 patients. The stone recurrence rate was 33.3% (5 patients)
      after a median follow-up of 40 months (range 14 to 132). Recurrent stones were
      treated with extracorporeal shock wave lithotripsy. CONCLUSIONS: The results of
      our study have demonstrated that percutaneous treatment of large upper tract
      stones after urinary diversion offers a high success rate with minimal morbidity.
      However, regular follow-up after treatment is recommended.

PMID- 16979746
TI  - Strong significant correlation between MMP-9 and systemic symptoms in patients
      with localized renal cell carcinoma.
AB  - OBJECTIVES: To identify a relationship between clinical symptoms and matrix
      metalloproteinase (MMP)-2 and MMP-9, tissue inhibitor of metalloproteinase (TIMP)
      1 and TIMP-2, and membrane type MMP-1. METHODS: Tumor samples from 232 patients
      with renal cell carcinoma with no distant metastasis were immunohistochemically
      stained for MMP-2 and MMP-9, TIMP-1 and TIMP-2, and membrane type MMP-1. The
      immunoreactivity of these factors was analyzed by semiquantitative multivariate
      analysis for correlation with clinical symptoms. RESULTS: Patard's criteria were
      used to classify symptoms at initial tumor clinical presentation, with three
      groups defined: S1, S2, and S3. The cancer-specific 5-year survival rate was
      88.7%, 74.7%, and 67.6% for S1 (145 patients), S2 (69 patients), and S3 (18
      patients), respectively (P = 0.0015). Multiple logistic regression analysis of
      preference was used to determine whether differences in the contribution of the
      symptoms were statistically significant. A maximal tumor diameter of 40 mm or
      greater and positive venous invasion were associated with a 262% and 281%
      increase in the odds of local symptoms, respectively. MMP-9 positive cases were
      associated with a 2979% increase in the odds of systemic symptoms with
      significance. CONCLUSIONS: This study found a strong significant correlation
      between the histopathologic expression of MMP-9 and the systemic symptoms of
      renal cell carcinoma. We propose the histopathologic measurement of MMP-9 as a
      useful tool for assessing the prognosis of patients with renal cell carcinoma
      with systemic symptoms.

PMID- 16979747
TI  - Dysuria at onset of interstitial cystitis/painful bladder syndrome in women.
AB  - OBJECTIVES: In an ongoing national study of women to identify risk factors for
      interstitial cystitis/painful bladder syndrome (IC/PBS), dysuria was identified
      at the onset of IC/PBS in a small majority and the evidence for urinary tract
      infection was evaluated. METHODS: In women with IC/PBS of 12 months' duration or
      less, symptoms and pertinent laboratory tests at onset were assessed by telephone
      interview and medical record review. RESULTS: Of 138 women, 75 (54%) reported
      that they had started to experience burning or pain on urination at the onset of
      IC/PBS. Of those with urine cultures, 12 (34%) of 35 women with dysuria versus 1
      (5%) of 21 without dysuria yielded a uropathogen (P = 0.01). Similarly, the
      microscopic white blood cell count and dipstick nitrites and leukocyte esterase
      were each significantly more common in the urine samples of those with dysuria
      than in those without. Additionally, 7 of 75 of those with dysuria versus 1 of 62
      without dysuria reported chills or fever at the onset of IC/PBS. Using various
      definitions, the prevalence of urinary tract infection at the onset of IC/PBS, at
      a minimum, was 16% to 33% of those with dysuria versus less than 2% of those
      without dysuria (P < or = 0.003). CONCLUSIONS: A slight majority of women with
      IC/PBS reported dysuria at onset of their IC/PBS symptoms. The available
      laboratory data have suggested that dysuria may be a sensitive indicator of
      urinary tract infection at the onset of IC/PBS; however, its specificity is as
      yet undetermined.

PMID- 16979748
TI  - Characteristics and outcomes of patients with carcinoma in situ only at radical
      cystectomy.
AB  - OBJECTIVES: To describe the cancer-specific outcomes of patients with pathologic
      carcinoma in situ (CIS) only at radical cystectomy. METHODS: The records of 812
      consecutive patients who underwent radical cystectomy and pelvic lymphadenectomy
      for bladder transitional cell carcinoma at three U.S. academic centers were
      reviewed. Of the 812 patients, 99 (12%) had CIS only at radical cystectomy.
      RESULTS: The distribution of clinical stage for the 99 patients with CIS only at
      radical cystectomy was as follows: 47% of patients had CIS only, 8% had cT1, 15%
      had cT1 plus CIS, 10% had cT2, 13% had cT2 plus CIS, 6% had cTa, and 1% had Ta
      plus CIS. Two patients had lymphovascular invasion in the radical cystectomy
      specimen, and three had metastases to the lymph nodes. The actuarial recurrence
      free survival estimates were 89.8% (95% confidence interval [CI] 83.0% to 96.6%)
      at 3 years and 83.0% (95% CI 73.2% to 92.8%) at 5 and 7 years after radical
      cystectomy. Six patients (6%) had died of bladder cancer at analysis and 13 (13%)
      had died of other causes without evidence of disease recurrence. The actuarial
      disease-specific survival estimates were 95.8% (95% CI 91.2% to 99.9%) at 3
      years, 90.7% (95% CI 82.4% to 98.9%) at 5 years, and 87.2% (95% CI 76.8% to
      97.5%) at 7 years after surgery. On univariate Cox regression analyses, only
      metastasis to lymph nodes was associated with bladder cancer recurrence and death
      (P <0.001). CONCLUSIONS: Disease control seemed durable for patients with
      pathologic CIS only at radical cystectomy in the absence of metastases to the
      lymph nodes, even in the case of failure after intravesical therapy.

PMID- 16979749
TI  - Diet and benign prostatic hyperplasia: implications for prevention.

PMID- 16979751
TI  - Testing anonymous link procedures for follow-up of adolescents in a school-based
      trial: the EU-DAP pilot study.
AB  - OBJECTIVE: To study the feasibility of an anonymous coding procedure linking
      longitudinal information in a multi-center trial of substance abuse prevention
      among adolescents. METHODS: A school-based survey with re-test procedure was
      conducted among 485 students (mean age 13.8 years) from three countries at four
      study centers in order to study accuracy and repeatability of a self-generated
      anonymous code. RESULTS: Errors affected 18% of codes and 3% of all digits
      required for the code generation, with highest figures for two of the seven
      generation items. Sixty-one percent of the codes generated at the test were
      repeated identically at the re-test. Seventy-six percent of the codes could be
      linked excluding the 2 digits with the highest error rate in code generation,
      while 92% were linked using the best combination of the remaining seven or six
      digits. There was substantial variation between the centers in the results.
      CONCLUSIONS: Self-generation of anonymous codes is a feasible, but not a very
      efficient procedure to link longitudinal data among adolescents. Easy derivation
      and iterative matching procedures are crucial for achieving high efficiency of
      this type of anonymous linkage.

PMID- 16979752
TI  - Artificial insemination increases the probability of a male calf in dairy and
      beef cattle.
AB  - The objective of this study was to determine if natural mating affected secondary
      sex ratio. Data consisting of 642,401 calving records from the Irish national
      database, during the years 2002-2005, were used in the analysis. Factors
      affecting the logit of the probability of a male calf being born were determined
      using multiple regression generalised estimating equations with sire of the calf
      included as a repeated effect. Month of the year at calving, sex of the previous
      calf born within dam, breed of service sire, parity of dam and type of mating
      (i.e., natural or artificial insemination) significantly (P<0.05) affected the
      likelihood of a male calf being born. Male calves were more likely to be born in
      the warmer months of the year, when the sex of the previous calf born to the same
      dam was male, in older cows and when the service sire was a beef breed. No
      significant interaction between the main effects existed. The odds of a male calf
      being born, following adjustment for confounding effects, varied from 1.04 to
      1.08 (P<0.01) across the years of analysis when artificial insemination was used
      compared to natural mating. This equates to a 1% unit increase in the probability
      of a male calf being born following artificial insemination.

PMID- 16979750
TI  - Progestins influence motivation, reward, conditioning, stress, and/or response to
      drugs of abuse.
AB  - Progesterone (pregn-4-ene-3,20-dione; P) and its metabolite 5alpha-pregnan-3alpha
      ol-20-one (3alpha,5alpha-THP) are secreted by ovaries, adrenals, and glial cells.
      3alpha,5alpha-THP in the midbrain ventral tegmental area mediates sexual
      receptivity of rodents through its actions at GABA(A), NMDA, and/or D(1)
      receptors. The extent to which 3alpha,5alpha-THP may influence anti-anxiety/anti
      stress effects, conditioning and/or reward through these substrates and/or by
      altering hypothalamic pituitary adrenal axis function is discussed. Biosynthesis
      of 3alpha,5alpha-THP occurs in responses to mating and may underlie some of the
      rewarding aspects of sexual behavior. Recent findings from our laboratory which
      demonstrate that progestins can enhance approach to novel stimuli, conditioning,
      and reinforcement are reviewed. How progestins' effects on these processes may
      underlie response to drugs of abuse is considered and new findings which
      demonstrate interactions between progestins and cocaine are presented.

PMID- 16979753
TI  - Use of information and communication technology (ICT) and perceived health in
      adolescence: the role of sleeping habits and waking-time tiredness.
AB  - The first aim for this paper was to examine gender and age differences in the
      intensity of usage of information and communication technology (ICT: computer for
      digital playing, writing and e-mailing and communication, and Internet surfing,
      and mobile phone). Second, we modelled the possible mediating role of sleeping
      habits and waking-time tiredness in the association between ICT usage and
      perceived health (health complaints, musculoskeletal symptoms, health status).
      The participants were 7292 Finns aged 12, 14, 16 and 18 years responding to a
      postal enquiry (response rate 70%). The results showed that boys played digital
      games and used Internet more often than girls, whose mobile phone usage was more
      intensive. Structural equation model analyses substantiated the mediating
      hypothesis: intensive ICT-usage was associated with poor perceived health
      particularly or only when it negatively affected sleeping habits, which in turn
      was associated with increased waking-time tiredness. The associations were gender
      specific especially among older adolescents (16- and 18-year olds). Intensive
      computer usage forms a risk for boys', and intensive mobile phone usage for
      girls' perceived health through the mediating links. Girls were vulnerable to the
      negative consequences of intensive mobile phone usage, as it associated with
      perceived health complaints and musculoskeletal symptoms both directly and
      through deteriorated sleep and increased waking-time tiredness. The results of
      gender-specific ICT usage and vulnerability are discussed as reflecting gendered
      psychophysiological, psychological and social developmental demands.

PMID- 16979754
TI  - RETRACTED: Structural Stability of RNA-Binding proteins through Computation of
      Cation-pi Interactions.
AB  - This article has been retracted consistent with Elsevier Policy on Article
      Withdrawal. Please see . The Publisher apologizes for any inconvenience this may
      cause.

PMID- 16979755
TI  - Assessment of hepatocellular function within PEG hydrogels.
AB  - Tissue-engineered therapies for liver failure offer the potential to augment or
      replace whole organ transplantation; however, fabrication of hepatic tissue poses
      unique challenges largely stemming from the complexity of liver structure and
      function. In this study, we illustrate the utility of highly-tunable,
      photopolymerizable poly(ethylene glycol) (PEG) hydrogels for 3D encapsulation of
      hepatic cells and highlight a range of techniques important for examining
      hepatocellular function in this platform. Owing to our long-term interest in
      incorporating proliferative progenitor cell types (e.g. hepatoblasts, oval cells,
      or cells derived from embryonic stem cells) and maintaining the phenotype of
      differentiated cells, we explored the behavior of bipotential mouse embryonic
      liver (BMEL) cells as a model progenitor cell and mature, fully differentiated,
      primary hepatocytes in this biomaterial system. We demonstrated the importance of
      cell-cell and cell-matrix interactions in the survival and function of these cell
      types, and the capacity to influence encapsulated cell phenotypes through
      modulation of hydrogel characteristics or gene silencing. Additionally, we
      demonstrated imaging techniques critical for the in situ assessment of
      encapsulated hepatocyte function combined with the ability to control cellular
      organization and overall architecture through microscale patterning technologies.
      Further analysis of liver progenitor as well as mature hepatocyte processes
      within the versatile PEG hydrogel platform will aid in the development of tissue
      engineered implantable liver systems.

PMID- 16979756
TI  - Synthesis of two-component injectable polyurethanes for bone tissue engineering.
AB  - The advent of injectable polymer technologies has increased the prospect of
      developing novel, minimally invasive arthroscopic techniques to treat a wide
      variety of ailments. In this study, we have synthesised and evaluated a novel
      polyurethane-based injectable, in situ curable, polymer platform to determine its
      potential uses as a tissue engineered implant. Films of the polymers were
      prepared by reacting two pentaerythritol-based prepolymers, and characterised for
      mechanical and surface properties, and cytocompatibility. This polymer platform
      displayed mechanical strength and elasticity superior to many injectable bone
      cements and grafts. Cytotoxicity tests using primary human osteoblasts, revealed
      positive cell viability and increased proliferation over a period of 7 days in
      culture. This favourable cell environment was attributed to the hydrophilic
      nature of the films, as assessed by dynamic contact angle (DCA) analysis of the
      sample surfaces. The incorporation of beta-TCP was shown to improve mechanical
      properties, surface wettability, and cell viability and proliferation, compared
      to the other sample types. SEM/EDX analysis of these surfaces also revealed
      physicochemical surface heterogeneity in the presence of beta-TCP. Based on
      preliminary mechanical analysis and cytotoxicity results, these injectable
      polymers may have a number or potential orthopaedic applications; ranging from
      bone glues to scaffolds for bone regeneration.

PMID- 16979757
TI  - Development and in vitro evaluation of a thiomer-based nanoparticulate gene
      delivery system.
AB  - Chitosan-thiobutylamidine was developed and evaluated as a novel tool for gene
      delivery. The conjugate, displaying 299.1+/-11.5 micromol free thiol groups per
      gram polymer, formed coacervates with pDNA at a mean size of 125 nm and a zeta
      potential of +9 mV. Thiol groups, being susceptible for oxidation, were
      immobilised on the polymeric backbone of chitosan in order to introduce the
      property of extracellular stability and intracellular pDNA release by forming
      reversible disulfide bonds. The integrity of the new particles was compared to
      unmodified chitosan under simulated physiological conditions. Within 10h, pDNA
      was completely released from chitosan-DNA particles while only 12% were released
      from the thiomer-based particles. At pH 7, the amount of thiol groups
      significantly (p<0.05) decreased by more than 25% within 6h. In contrast, in a
      reducing environment as found intracellularly, chitosan-thiobutylamidine-DNA
      nanoparticles dissociated continuously, liberating approximately 50% of pDNA
      within 3h. Transfection studies performed in a Caco2 cell culture evinced the
      highest efficiency for chitosan-thiobutylamidine-DNA nanoparticles in combination
      with a glycerol shock solution. The combination of improved stability, enhanced
      pDNA release under reducing conditions, and higher transfection efficiency
      identifies chitosan-thiobutylamidine as a promising new vector for gene delivery.

PMID- 16979758
TI  - Signature combinatorial splicing profiles of rat cardiac- and smooth-muscle
      Cav1.2 channels with distinct biophysical properties.
AB  - l-type (Ca(v)1.2) voltage-gated calcium channels play an essential role in muscle
      contraction in the cardiovascular system. Alternative splicing of the pore
      forming Ca(v)1.2 subunit provides potent means to enrich the functional diversity
      of the channels. There are 11 alternatively spliced exons identified in rat
      Ca(v)1.2 gene and random rearrangements may generate up to hundreds of
      combinatorial splicing profiles. Due to such complexity, the real combinatorial
      splicing profiles of Ca(v)1.2 have not been solved. This study investigated
      whether the 11 alternatively spliced exons are spliced randomly or linked and if
      linked, how many combinatorial splicing profiles can be arranged in cardiac- and
      smooth-muscle cells. By examining three full-length cDNA libraries of the
      Ca(v)1.2 transcripts isolated from rat heart and aorta, our results showed that
      the arrangements of some of the alternatively spliced exons are tissue-specific
      and tightly linked, giving rise to only 41 alternative combinatorial profiles, of
      which 29 have not been reported. Interestingly, the 41 combinatorial profiles
      were distinctively distributed in the three Ca(v)1.2 libraries and the one named
      "heart 1-50" contained unexpected splice variants. Significantly, the tissue
      specific cardiac- and smooth-muscle combinatorial splicing profiles of Ca(v)1.2
      channels demonstrated distinct electrophysiological properties that may help
      rationalize the differences observed in native currents. The unique sequences in
      these tissue-specific splice variants may provide the potential targets for drug
      design and screening.

PMID- 16979759
TI  - Dietary PBDE intake: a market-basket study in Belgium.
AB  - A food market-basket, representative for the general Belgian population,
      containing various meat, fish and dairy food products, was assembled and analysed
      for its polybrominated diphenyl ether (PBDE) content. Additionally, fast food
      samples were also investigated. Based on the measured PBDE levels, an average
      daily dietary intake estimate of PBDEs was calculated. Of all foods analysed,
      fish had the highest average sum of PBDE levels (BDEs 28, 47, 99, 100, 153, 154,
      and 183; 460 pg/g ww), followed by dairy products and eggs (260 pg/g ww), fast
      food (86 pg/g ww) and meat products (70 pg/g ww). One fresh salmon filet had the
      highest total concentration of PBDEs (2360 pg/g ww), whereas levels in steak and
      chicken breast were the lowest of all foods analysed. BDE 209 was never found
      above LOQ in any food. PBDE intake calculations were based on the average daily
      food consumption in Belgium and were estimated between 23 and 48 ng/day of total
      PBDEs (lower and upper bound). This value is in accordance with what was
      previously reported for diets from geographical distinct areas, such as Canada,
      Finland, Spain, Sweden and the UK. Although it is only a minor constituent of the
      Belgian diet, fish is the major contributor to the total daily PBDE-intake
      (around 40%) due to the high PBDE levels in this type of food. Although low
      contaminated, meat products account for around 30% of the total dietary intake of
      PBDEs. Dairy products and eggs contribute to a lesser degree (less than 30%).

PMID- 16979760
TI  - Nocardia species infections in a large county hospital in Miami: 6 years
      experience.
AB  - A review of all cases of nocardiosis in a large hospital in South Florida over
      the last 6 years was conducted. There were 25 cases of nocardiosis and 76% of
      them were also infected with HIV. Of the HIV infected patients, all of them had
      CD4 counts less than 100 cells/mm(3) and most cases were localized in the lungs.

PMID- 16979761
TI  - Mantoux Test as a model for a secondary immune response in humans.
AB  - The Mantoux Test (MT) is a classical delayed-type hypersensitivity (DTH) response
      to the intradermal injection of tuberculin purified protein derivative (PPD). It
      represents a cutaneous T cell mediated memory recall immune response. The test is
      typically used to determine immunity to tuberculosis in humans and positive
      reactions develop in individuals previously exposed to Mycobacterium
      tuberculosis, and those immunised with the Bacillus of Calmette and Guerin (BCG)
      vaccine. In view of its relative accessibility human skin represents a convenient
      tissue for the investigation of human immune responses. Using the MT, we have
      been able to determine that significant cellular proliferation and clonal
      expansion occur at the site of antigen deposition in the skin. Furthermore, cells
      undergoing proliferation in the skin also undergo accelerated differentiation.
      Taken together with other studies, in humans and in mice, these observations shed
      new light on the importance of the microenvironment at the site of the immune
      response for the proliferation and differentiation of memory T cells.

PMID- 16979762
TI  - A prospective study to determine the incidence of atopy in children undergoing
      adenotonsillectomy for obstructive sleep apnea.
AB  - OBJECTIVES: To investigate the relationship between adenotonsillar hypertrophy
      seen in pediatric obstructive sleep apnea and upper airway allergy to airborne
      allergens. METHODS: A prospective study of Radioallergosorbent (RAST) tests to
      common airborne allergens in children (<16 years old) undergoing
      adenotonsillectomy for obstructive sleep apnea in a London Teaching Hospital.
      RESULTS: 20.9% of patients had a positive RAST result to house dust mite, 2.8% to
      cat hair, 0% to mixed feather, 7.8% to mixed grass pollen and 3.8% to dog hair.
      CONCLUSIONS: This study does not support the hypothesis that the adenotonsillar
      hypertrophy seen in pediatric patients with obstructive sleep apnea is
      contributed to by allergy to airborne allergens. It is possible that there is a
      localized allergic reaction in the upper respiratory tract mucosa which is not
      apparent on an assay of systemic IgE.

PMID- 16979763
TI  - The mammalian subiculum: contrasting and complementary in vivo and in vitro
      approaches to subicular function.

PMID- 16979765
TI  - Early androgen treatment influences the pattern and amount of locomotion activity
      differently and sexually differentially in an animal model of ADHD.
AB  - Higher testosterone level in males is one of the most obvious possibilities for
      the development of a clear gender difference in ADHD. The present study focused
      on the influence of excessive androgen exposure in the developmental stage on the
      hyperactivity feature of ADHD. The study used the spontaneously hypertensive rat
      (SHR) as an animal model. The amount of locomotion activity previously used as an
      over-activity measure in the SHR has resulted in a complicated picture. While the
      general activity level of SHR was significantly higher than its progenitor-the
      Wistar Kyoto rat (WKY), comparative differences with the Wistar rat could be
      observed only under certain experimental conditions. The present study applied
      the scaling approach to assess open field behaviors from a qualitative aspect.
      Although SHR and Wistar rats showed similar locomotion amounts, movement patterns
      differed significantly, as indicated by the spatial scaling exponent. Androgen
      treatment during the early postnatal developmental stage significantly increased
      total path lengths only in the male SHR. Effects of the hormone manipulation were
      not expressed in the scaling measurement. The scaling approach conclusively
      provides a different aspect of open field behaviors and also reacts differently
      as the total path length to excessive early testosterone exposure.

PMID- 16979764
TI  - Episodic vestibular disruption following ablation of the inferior olive in rats:
      behavioral correlates.
AB  - The experiments herein investigate whether the behavioral responses to transient
      and episodic vestibular disruption and permanent ablation are distinct in the
      absence of climbing fiber input. Subjects in group 1 received an IP injection of
      PBS followed by an IP injection of niacinamide. Seven days later these rats
      received the first of 3 serial transtympanic injections of TTX on the same side
      with 7 days between each injection. Following each TTX injection rats displayed
      unilateral vestibular symptoms that persisted beyond 48h. Spontaneous barrel
      rolling behavior was not observed. Group 2 subjects received an IP injection of 3
      acetylpyridine (3-AP)+niacinamide followed by the same TTX regimen as group 1.
      Following each TTX injection vestibular symptoms (severe body twisting and
      persistent spontaneous barrel rolling) emerged rapidly (<15min) and resolved by
      72h. Group 3 subjects received an IP injection of 3-AP+niacinamide and 7 days
      later a single unilateral transtympanic injection of sodium arsanilate. Rats in
      group 3 developed vestibular symptoms similar to those observed in group 2
      although there was no resolution of these symptoms. The results indicate that TTX
      has a rapid rate of infiltration and blockade of the VIIIth nerve that persists
      for >48h and then completely resolves. The contrast in vestibular symptoms
      between groups 1 and 2 suggest that climbing fibers are recruited soon after
      onset of vestibular disruption and play a role in attenuating the severity of
      vestibular symptoms associated with transient/episodic vestibular disruption.

PMID- 16979766
TI  - Nicotine administration effects on feeding and cocaine-amphetamine-regulated
      transcript (CART) expression in the hypothalamus.
AB  - In previous studies food intake and meal size significantly decreased in rats two
      days after injecting 4 mg/kg/day nicotine tartrate. Food intake returned to
      normal after nine days of continued nicotine treatment, when reduced meal size is
      countered by an increase in meal number. Nicotine also reduced body weight after
      nicotine injection and body weight remained low after nine days. To begin
      characterizing the mechanism that modulates these changes in feeding behavior
      and/or body weight during nicotine exposure the transcript levels for agouti
      related protein (AGRP), cocaine-amphetamine-regulated transcript (CART),
      corticotropin releasing hormone receptor one (CRH-R1), melanocortin receptors
      three and four (MC3R/4R), neuropeptide Y (NPY), NPY Y1 and Y5 receptors and/or
      pro-opiomelanocortin (POMC) were analyzed in the arcuate (ARC), dorsomedial (DMN)
      and paraventricular (PVN)/periventricular (PE) hypothalamic nuclei on the second
      and ninth day of saline or nicotine treatment. Results show that the transcript
      levels of the anorexigenic molecule CART increased in the PVN and/or PE two days
      after nicotine treatment but after nine days CART levels equalize. In contrast,
      nine days of nicotine treatment reduced CART levels in the DMN as compared to
      saline controls. To investigate CART's role in regulating feeding, infusion of
      CART (55-102) into the third ventricle reduced food intake and meal size. These
      results are consistent with nicotine modulating feeding behavior and body weight,
      in part, by affecting CART transcript levels in the DMN, PVN and/or PE.

PMID- 16979767
TI  - Simulation model estimates of test accuracy and predictive values for the Danish
      Salmonella surveillance program in dairy herds.
AB  - The Danish government and cattle industry instituted a Salmonella surveillance
      program in October 2002 to help reduce Salmonella enterica subsp. enterica
      serotype Dublin (S. Dublin) infections. All dairy herds are tested by measuring
      antibodies in bulk tank milk at 3-month intervals. The program is based on a well
      established ELISA, but the overall test program accuracy and misclassification
      was not previously investigated. We developed a model to simulate repeated bulk
      tank milk antibody measurements for dairy herds conditional on true infection
      status. The distributions of bulk tank milk antibody measurements for infected
      and noninfected herds were determined from field study data. Herd infection was
      defined as having either >or=1 Salmonella culture-positive fecal sample or >or=5%
      within-herd prevalence based on antibody measurements in serum or milk from
      individual animals. No distinction was made between Dublin and other Salmonella
      serotypes which cross-react in the ELISA. The simulation model was used to
      estimate the accuracy of herd classification for true herd-level prevalence
      values ranging from 0.02 to 0.5. Test program sensitivity was 0.95 across the
      range of prevalence values evaluated. Specificity was inversely related to
      prevalence and ranged from 0.83 to 0.98. For a true herd-level infection
      prevalence of 15%, the estimate for specificity (Sp) was 0.96. Also at the 15%
      herd-level prevalence, approximately 99% of herds classified as negative in the
      program would be truly noninfected and 80% of herds classified as positive would
      be infected. The predictive values were consistent with the primary goal of the
      surveillance program which was to have confidence that herds classified negative
      would be free of Salmonella infection.

PMID- 16979768
TI  - High-rate ferrous iron oxidation by immobilized Acidithiobacillus ferrooxidans
      with complex of PVA and sodium alginate.
AB  - By four different methods, Acidithiobacillus ferrooxidans cells were immobilized
      by the complex of PVA and sodium alginate. The beads formed by these different
      methods were evaluated in terms of relative mechanical strength, biological
      activity, dilatability, and so on. The results indicate that the technique
      utilizing the complex of PVA and sodium alginate crosslinked with Ca(NO(3))(2) is
      more appropriate for the immobilization of A. ferrooxidans than any others. So
      the PVA-calcium nitrate beads were used in batch and continuous culture. A
      maximum ferrous iron oxidation rate of 4.6 g/l/h was achieved in batch culture.
      Long-time performance of packed-bed bioreactor was evaluated systematically over
      40 days, depending on the conversion ratio of ferrous iron and the residence
      time. At a residence time of 2.5 h, 96% of the initial ferrous iron was oxidized.
      This study shows this new immobilization technique will be a feasible and
      economical method for A. ferrooxidans.

PMID- 16979769
TI  - Dynamic changes in Robo2 and Slit1 expression in adult rat dorsal root ganglion
      and sciatic nerve after peripheral and central axonal injury.
AB  - Robos are transmembrane receptors that mediate Slit signaling to repel growth
      cone outgrowth and neural migration in the developing central nervous system.
      Their distribution and function in the peripheral nervous system remains unclear.
      In the present study, we examined expression of Slit1 and Robo2 in adult rat
      dorsal root ganglion (DRG), spinal cord and sciatic nerve after peripheral nerve
      injury (axotomy). In control rats, Slit1 and Robo2 mRNA and protein were
      expressed at basic levels in the L5 and L6 DRGs. Sciatic transection resulted in
      a significant up-regulation of both Robo2 and Slit1 mRNA and protein (p<0.05
      versus control). The peak of Slit1 and Robo2 expression occurred at days 7 and
      14, respectively, and returned to control levels at days 28 and 21 post-axotomy,
      respectively. By contrast, injury to the central axons of the DRG by dorsal
      rhizotomy did not up-regulate Slit1 and Robo2 expression. Robo2 staining was
      stronger in small diameter neurons than in large diameter neurons in control DRG.
      Interestingly, post-axotomy, Robo2 immunostaining increased in the large diameter
      neurons and the number of Robo2 positive large diameter neurons increased
      significantly relative to controls. Non-neuronal cells surrounding the primary
      sensory neurons, including the satellite cells, were Slit1-positive, and Slit1
      protein was expressed in the myelin sheath and non-neural cells in both intact
      and degenerating sciatic nerve axons. Sciatic nerve transection also led to an
      accumulation of Slit1 protein in peripheral region of the traumatic neuroma. In
      conclusion, we report an altered expression and redistribution of Robo2 and Slit1
      in the DRG and sciatic nerve trunk after peripheral axotomy. Our results indicate
      that Slit1 and Robo2 likely play an important role in regeneration after
      peripheral nerve injury.

PMID- 16979770
TI  - Identification of a cell polarity-related protein, Lin-7B, as a binding partner
      for a Rho effector, Rhotekin, and their possible interaction in neurons.
AB  - Rhotekin, an effector of Rho, is highly expressed in the brain but its
      function(s) in neurons is almost unknown. In an attempt to define the properties
      of Rhotekin in neuronal cells, we focused on its interaction with polarity
      related molecules. In the present study, we identified a PDZ protein, Lin-7B, as
      a binding partner for Rhotekin by yeast two-hybrid screening of human brain cDNA
      library. We then found that Rhotekin interacts with Lin-7B in in vitro pull-down
      assays, and forms an immunocomplex in COS7 cells and the rat brain. The C
      terminal three amino acids of Rhotekin were essential for the interaction with
      Lin-7B. Their binding affinity became increased in the presence of active RhoA in
      the COS7 cell expression system. In addition, immunohistochemical analyses
      demonstrated that Lin-7 as well as Rhotekin is enriched in neurons. These results
      suggest that Lin-7 plays some role in neuronal functions in concert with
      Rho/Rhotekin signals.

PMID- 16979771
TI  - Detection of multiple virulence-associated genes in Listeria monocytogenes
      isolated from bovine mastitis cases.
AB  - Clinical samples (n=725) were collected from bovines (n=243) which were positive
      for mastitis using the California mastitis test (CMT) and somatic cell count
      (SCC). The clinical samples comprising blood (n=239), milk (n=243), and faecal
      swabs (n=243) were examined for the presence of pathogenic Listeria spp.
      Isolation of the pathogen was done using selective enrichment in University of
      Vermont Medium and plating onto Dominguez-Rodriguez isolation agar. Confirmation
      of the isolates was based on biochemical tests and Christie, Atkins, Munch
      Petersen (CAMP) test followed by pathogenicity testing. Pathogenicity of the
      isolates was tested by phosphatidylinositol-specific phospholipase C (PI-PLC)
      assay as well as in vivo tests namely, chick embryo and mice inoculation tests.
      The isolates were subjected to PCR assay for five virulence-associated genes,
      plcA, prfA, hlyA, actA and iap. Listeria spp. were isolated from 12 (1.66%)
      samples. Of these 4 (0.55%) and 1 (0.14%) were confirmed as Listeria
      monocytogenes and Listeria ivanovii, respectively. L. monocytogenes and L.
      ivanovii were recovered from milk samples (2) and faecal (3) of mastitic cattle
      (3) and buffaloes (2). L. monocytogenes recovered from the milk of mastitic
      cattle and L. ivanovii from the faecal swab of buffalo turned out to be
      pathogenic. However, the remaining three hemolytic isolates exhibiting positive
      CAMP test turned out to be negative in PI-PLC assay, chick embryo and mice
      inoculation. L. monocytogenes and L. ivanovii isolates characterized as
      pathogenic by PI-PLC assay and in vivo pathogenicity tests were found to possess
      all the five virulence-associated genes and three genes, plcA, prfA and actA
      respectively. The remaining three hemolytic but non-pathogenic L. monocytogenes
      isolates were negative for plcA by PCR. It seems that the plcA gene and its
      expression (in the PI-PLC assay) have an important role as virulence determinants
      in pathogenic Listeria spp. In conclusion, the PI-PLC assay and virulence genes
      targeted PCR (plcA, prfA and hlyA genes for L. monocytogenes and plcA, prfA and
      actA genes for L. ivanovii) hold a good promise as rapid and reliable in vitro
      alternatives to in vivo pathogenicity tests.

PMID- 16979772
TI  - Increased permeability of human endothelial cell line EA.hy926 induced by
      hantavirus-specific cytotoxic T lymphocytes.
AB  - Hantavirus infection causes two human diseases, hemorrhagic fever with renal
      syndrome and hantavirus pulmonary syndrome. The typical feature of these diseases
      is increased permeability in microvascular beds in the kidneys and the lungs,
      respectively. The mechanism of capillary leakage, however, is not understood.
      Some evidence suggests that hantavirus disease pathogenesis is immunologically
      mediated by cytotoxic T lymphocytes and other immune cells in target organs
      producing inflammatory cytokines. In this study we examined the roles of virus
      specific cytotoxic T lymphocytes in increased permeability of human endothelial
      cells infected with hantavirus. We used a human CD8(+) hantavirus-specific
      cytotoxic T lymphocyte line, 1A-E2, specific for the HLA-A24-restricted epitope
      in Sin Nombre and Puumala virus G2 protein, and the human endothelial cell line,
      EA.hy926 that expresses HLA-A24 molecule. The cytotoxic T lymphocyte line
      recognized and lysed target cells infected with Sin Nombre virus, and in
      transwell permeability assays increased permeability of EA.hy926 cell monolayer
      infected with Sin Nombre virus or recombinant adenovirus expressing the Sin
      Nombre virus G2 protein. These results suggest that cytotoxic T lymphocyte
      activity contribute to capillary leakage observed in patients with hantavirus
      pulmonary syndrome or hemorrhagic fever with renal syndrome.

PMID- 16979773
TI  - Dynamics of a hepatitis B virus e antigen minus population ascribed to genotype F
      during the course of a chronic infection despite the presence of anti-HBs
      antibodies.
AB  - The in vivo evolution of genotype F HBV variants was recorded in a chronically
      infected patient throughout a 3-year observation period. Fluctuating levels of
      HBs Ag and anti-HBs antibodies were recorded, both of them cocirculating in
      peripheral blood samples at given times. Fifty S gene derived clones were
      sequenced and phylogenetically analyzed. As expected, some amino acid
      replacements within the S ORF were also observed within the P ORF while others
      were silent for the former. Such change was statistically significant for both S
      and P overlapping genes, which clearly indicates the appearance of a positive
      selection pressure. Supporting this notion, amino acid replacements were
      documented at both B and T cell epitopes in samples from 1997 and 1998. Several
      mutations were documented within and outside the "a" determinant in the major
      hydrophilic region. Such substitutions might have resulted from the attempt of
      HBV to evade both humoral and/or cellular immune response. To the best of our
      knowledge this unusual profile of HBV variants in presence of usually
      "neutralizing" anti-HBs antibodies was examined in vivo for the first time.

PMID- 16979774
TI  - Cardiovascular risk factors in pre-pubertal Malays: effects of diabetic
      parentage.
AB  - Diabetes prevalence is increasing rapidly in Asian populations but the influence
      of a family history of diabetes on cardiovascular risk is unknown. To assess this
      relationship, 120 urban-dwelling Malays were recruited to a cross-sectional case
      control study. Sixty were pre-pubertal children, 30 of diabetic parentage (Group
      1) and 30 with no diabetes family history (Group 2). Group 1 and 2 subjects were
      the offspring of adults with (Group 3) or without (Group 4) type 2 diabetes.
      Subjects were assessed for clinical and biochemical variables defining
      cardiovascular risk. Principal component analysis assessed clustering of
      variables in the children. Group 1 subjects had a higher mean waist:hip ratio,
      diastolic blood pressure and HbA(1c) than those in Group 2, and a lower HDL:total
      cholesterol ratio (P<0.03). Although there were no correlations between Group 1
      and 3 subjects for cardiovascular risk variables, significant associations were
      found in Groups 2 and 4, especially HbA(1c) and insulin sensitivity (P< or
      =0.004). Of five separate clusters of variables (factors) identified amongst the
      children, the strongest comprised diabetic parentage, HbA(1c), insulin
      sensitivity and blood pressure. Features of the metabolic syndrome are becoming
      evident in the young non-obese children of diabetic Malays, suggesting that
      lifestyle factors merit particular attention in this group.

PMID- 16979775
TI  - HCV and steatosis in children.

PMID- 16979776
TI  - The intestinal flora and bacterial infection in cirrhosis.

PMID- 16979777
TI  - Neutralizing antibodies to interferon alpha in a chronic hepatitis C patient non
      responder to pegylated interferon.

PMID- 16979778
TI  - The role of JNK2 in toxic liver injury.
AB  - Tumor necrosis factor-induced toxic liver injury results from JNK2-dependent
      activation of caspase-8 and the mitochondrial death pathway. Wang Y, Singh R,
      Lefkowitch JH, Rigoli RM, Czaja MJ. In vitro studies of hepatocytes have
      implicated over-activation of c-Jun N-terminal kinase (JNK) signaling as a
      mechanism of tumor necrosis factor-alpha (TNF)-induced apoptosis. However, the
      functional significance of JNK activation and the role of specific JNK isoforms
      in TNF-induced hepatic apoptosis in vivo remain unclear. JNK1 and JNK2 function
      was, therefore, investigated in the TNF-dependent,
      galactosamine/lipopolysaccharide (GalN/LPS) model of liver injury. The toxin GalN
      converted LPS-induced JNK signaling from a transient to prolonged activation.
      Liver injury and mortality from GalN/LPS was equivalent in wild-type and jnk1-/-
      mice but markedly decreased in jnk2-/- mice. This effect was not secondary to
      down-regulation of TNF receptor 1 expression or TNF production. In the absence of
      jnk2, the caspase-dependent, TNF death pathway was blocked, as reflected by the
      failure of caspase-3 and -7 and poly(ADP-ribose) polymerase cleavage to occur.
      JNK2 was critical for activation of the mitochondrial death pathway, as in jnk2-/
      mice Bid cleavage and mitochondrial translocation and cytochrome c release were
      markedly decreased. This effect was secondary to the failure of jnk2-/- mice to
      activate caspase-8. Liver injury and caspase activation were similarly decreased
      in jnk2 null mice after GalN/TNF treatment. Ablation of jnk2 did not inhibit
      GalN/LPS-induced c-Jun kinase activity, although activity was completely blocked
      in jnk1-/- mice. Toxic liver injury is, therefore, associated with JNK over
      activation and mediated by JNK2 promotion of caspase-8 activation and the TNF
      mitochondrial death pathway through a mechanism independent of c-Jun kinase
      activity. [Abstract reproduced by permission of J Biol Chem 2006;281:15258-67].

PMID- 16979779
TI  - Biliary candida infections in primary sclerosing cholangitis.
AB  - BACKGROUND/AIMS: Patients with Primary Sclerosing Cholangitis (PSC) frequently
      develop dominant stenoses of the bile ducts and bacterial infections represent a
      major problem in such patients. In the present study, the role of fungal
      infections of the bile ducts has been evaluated. METHODS: In a prospective non
      randomized trial, in 67 consecutive patients with PSC, 148 bile samples, each
      taken at one endoscopic examination, were microbiologically analysed. RESULTS:
      Candida species were found in 8/67 patients whereas Aspergillus was not detected.
      Seven patients with biliary Candida had a dominant stenosis and one had a wide
      papillotomy with chronic ascending cholangitis. Altogether 7/49 of patients with
      dominant stenosis and 1/18 of patients without dominant stenosis had Candida in
      their bile. All patients with biliary Candida intermittently had received
      antibiotics and had advanced disease with cholestasis. Candida disappeared
      spontaneously in 2/7 patients, cleared after antifungal treatment in 2, and
      persisted in 3 patients. Patients with biliary Candida had more severe
      cholangitis with higher CRP and serum bilirubin compared to those without Candida
      infection. CONCLUSIONS: This is the first report on the identification of Candida
      species in the bile of patients with PSC. Apart from bacterial also fungal
      infection of the bile ducts should be considered in the treatment of such
      patients.

PMID- 16979780
TI  - Chromosomal clustering of nuclear genes encoding mitochondrial and chloroplast
      proteins in Arabidopsis.
AB  - We present a statistical analysis of chromosomal clustering among nuclear genes
      encoding mitochondrial or chloroplast proteins in Arabidopsis. For both
      organelles, the clustering was significantly increased above the expectation, but
      the clustering effect was weak, and most clusters were small and dispersed.
      Clustered genes showed coexpression but not more than expected, and no
      substantial synteny was detected in other eukaryotic genomes. We propose that the
      unexpected clustering results from continuous selection favoring chromosomal
      proximity of genes acting in the same organelle.

PMID- 16979781
TI  - Many gene and domain families have convergent fates following independent whole
      genome duplication events in Arabidopsis, Oryza, Saccharomyces and Tetraodon.
AB  - Genome duplication is potentially a good source of new genes, but such genes take
      time to evolve. We have found a group of "duplication-resistant" genes, which
      have undergone convergent restoration to singleton status following several
      independent genome duplications. Restoration of duplication-resistant genes to
      singleton status could be important to long-term survival of a polyploid lineage.
      Angiosperms show more frequent polyploidization and a higher degree of duplicate
      gene preservation than other paleopolyploids, making them well-suited to further
      study of duplication-resistant genes.

PMID- 16979782
TI  - Current concepts in RET-related genetics, signaling and therapeutics.
AB  - The receptor tyrosine kinase RET is expressed in cell lineages derived from the
      neural crest and has a key role in regulating cell proliferation, migration,
      differentiation and survival during embryogenesis. Germline and somatic mutations
      in RET that produce constitutively activated receptors cause the cancer syndrome
      multiple endocrine neoplasia type 2 and several endocrine and neural-crest
      derived tumors, whereas mutations resulting in nonfunctional RET or lower
      expression of RET are found in individuals affected with Hirschsprung disease.
      This review focuses on the genetics and molecular mechanisms underlying the
      different inherited human neural-crest-related disorders in which RET dysfunction
      has a crucial role and discusses RET as a potential therapeutic target.

PMID- 16979783
TI  - Mitochondrial DNA clonality in the dock: can surveillance swing the case?
AB  - Mitochondrial DNA (mtDNA) is a favoured tool of evolutionary biologists because
      its high mutation rate generates enough signal to make inferences about
      population history over short time frames. Furthermore, mtDNA inheritance is
      clonal, being transmitted only through the maternal line. This enables
      evolutionary histories to be assembled without the complexities introduced by
      biparental recombination. Recently, a single case of human biparental inheritance
      has been reported. Given this, and the role supposed clonal inheritance has had
      in shaping our knowledge of human population history, it is essential to
      establish a method for identifying any recombinant mtDNA molecules in our
      population. A reliable surveillance mechanism would either maintain our
      confidence in clonal inheritance or indicate the inaccuracy of our inferences.

PMID- 16979784
TI  - Computational characterization of multiple Gag-like human proteins.
AB  - In a genome-wide analysis, we have identified 85 human genes encoding 103 protein
      isoforms that resemble retroviral Gag proteins. These genes were domesticated
      from retrotransposons in at least five independent events during vertebrate
      evolution and were subsequently duplicated further in mammals. Structural
      insights into the mammalian proteins can be inferred by homology to Gag from
      viruses such as HIV; in turn, the cellular roles of the mammalian Gag homologs,
      such as apoptosis-related functions and binding to ubiquitin ligases, might hint
      at further functionality of viral Gag itself.

PMID- 16979785
TI  - An S-Plus function to calculate relative risks and adjusted means for regression
      models using natural splines.
AB  - We provide for generalized linear regression models that use natural cubic
      splines to model predictors an S-Plus function to calculate relative risks (RR),
      log relative risk (logRR), mean percent change (MPC) for continuous covariates
      modeled using a logarithmic link as well as adjusted means differences (MD) for
      the identity link. The function makes explicit use of the natural spline basis
      functions, the estimated coefficients for each natural spline basis function, and
      the fitted correlation matrix for the estimated coefficients and can thus
      accommodate any number of degrees of freedom. The main function produces a
      publication-quality graph of all of these quantities as compared to a user
      specified reference value as well as the associated confidence limits. In another
      function, specific values of these statistics comparing a vector of values of the
      independent variable to the reference value can be calculated rather than
      plotted.

PMID- 16979786
TI  - Challenges for cancer vaccine development.
AB  - The first generation of human cancer vaccines has been tested in phase III
      clinical trials, but only a few of these have demonstrated sufficient efficacy to
      be licensed for clinical use. This article reviews some of the mechanisms that
      could contribute to these limited clinical responses, and highlights the
      challenges faced for development of future vaccines.

PMID- 16979787
TI  - Imaging the renin-angiotensin system: an important target of anti-hypertensive
      therapy.
AB  - Multiphoton fluorescence microscopy allows visualization, manipulation, and
      quantification of the structure-function relationships between pharmacological
      interventions and their physiological effects. The application of these methods
      to live animals permits direct observation of acute physical responses that lack
      chemically detectable signals in the blood or urine and would otherwise remain
      unknown. With the use of special fluorescent dyes, chemical/hormonal responses
      may also be detected. The delivery and site-specific effects of drugs can be
      monitored in real-time. The capacity to simultaneously visualize both proximal
      and distal segments of the nephron permits observation of the dynamic processes
      within the living kidney and a quantitative assessment of the various operations.
      Consequently, a clinically valuable and pending application for multi-photon
      microscopy will be to provide real-time, quantitative imaging of basic organ
      functions and their responses to therapeutic intervention. Imaging of the intra
      renal renin content and enzymatic activity of renin in situ and in real-time is a
      new, more informative measure of RAS activity. Direct visualization of the
      molecular and cellular components of renin release signals and the interactions
      between the vascular endothelium, tubular epithelium, local mediators, and the
      renin producing cells provides great insight for drug development. Examples of
      how the effects of various RAS inhibitors can be visualized in the intact kidney
      are provided: including angiotensin converting enzyme inhibition (captopril),
      angiotensin II type 1 receptor blockade (olmesartan), and renin inhibition
      (aliskiren). The site-specific actions of diuretics, like furosemide, have also
      been visualized. Quantitative imaging of basic renal functions in health and
      disease can provide key information to assess the delivery and effects of
      pharmaceutical interventions.

PMID- 16979788
TI  - Improved peptide vaccine strategies, creating synthetic artificial infections to
      maximize immune efficacy.
AB  - Soon after it was realized that T-cells recognize their target antigens as small
      protein fragments or peptides presented by MHC molecules at the cell surface,
      these peptide epitopes have been tried as vaccines. Human testing of such
      vaccines, although protective in mouse models, has produced mixed results. Since
      these initial trials, there has been an tremendous increase in our understanding
      of how infectious organisms can induce potent immune responses. In this article
      we review the key changes in the design, formulation and delivery of synthetic
      peptide vaccines that are applied to improve peptide vaccine strategies.

PMID- 16979789
TI  - Activation of bombesin receptor subtype-3 stimulates adhesion of lung cancer
      cells.
AB  - Bombesin receptor subtype-3 (BRS-3) is an orphan G protein-coupled receptor
      having sequence homologies to gastrin-releasing peptide and neuromedin B
      receptors. [d-Phe6, beta-Ala11, Phe13, Nle14]bombesin(6-14) is known to act as a
      synthetic receptor agonist for BRS-3. To characterize BRS-3-mediated biological
      responses, we examined the effect of BRS-3 activation by [d-Phe6, beta-Ala11,
      Phe13, Nle14]Bn(6-14) on the adhesion of the small cell lung cancer NCI-N417
      cells that express native BRS-3. We found that the BRS-3 agonist stimulated
      adhesion of NCI-N417 cells in laminin-coated culture wells. The adhesion of the
      cells to laminin induced by BRS-3 activation was accompanied by an increase in
      vinculin-like immunoreactivity and diminished in the presence of an anti-beta1
      integrin antibody, suggesting that the receptor activation stimulates focal
      adhesion formation. We suggest that BRS-3 may be involved in invasion and
      metastasis of certain cancer cells, like small cell lung cancer cells, upon
      attachment to laminin.

PMID- 16979790
TI  - Relative velocities of DNAPL and aqueous phase plume migration.
AB  - Numerical simulation is used to examine the relative velocities of DNAPL and
      aqueous phase plumes in sandy aquifers where lateral spreading of DNAPL has
      occurred at the base of the aquifer. The scenario being modeled is one where a
      permeable aquifer is underlain by a sloping aquitard, which results in lateral
      migration of the DNAPL down the slope, in addition to lateral migration of an
      aqueous phase plume subject to a specified hydraulic gradient. A sensitivity
      analysis is presented to the impacts of both DNAPL properties and geologic
      properties. The most important chemical properties governing the relative
      velocities of the DNAPL and the shallow aqueous phase plume are the DNAPL
      viscosity and the aqueous component soil-water partition coefficient (Kd). The
      dip of the underlying aquitard was found to be relatively unimportant, at least
      for the range of values studied. The scenario under consideration can be
      important in conceptual model development and remedial design, as in certain
      cases DNAPL could be migrating in areas without the evidence of a well-developed
      aqueous phase plume. The implication of this work is that the absence of a
      shallow aqueous phase plume directly downgradient of a DNAPL source zone does not
      rule out the possibility of deep occurrences of DNAPL beyond the shallow
      monitoring well network. A further finding of this study is that the occurrence
      of a highly sorbing compound in groundwater at virtually any concentration may
      indicate the immediate upgradient presence of residual or pooled DNAPL.

PMID- 16979791
TI  - WITHDRAWN: Non-isothermal multiphase flow and reactive transport modelling of
      compacted bentonite simultaneously heated and hydrated.
AB  - Ahead of Print article withdrawn by publisher.

PMID- 16979792
TI  - Five-year surveillance of nosocomial infections in Ankara Training and Research
      Hospital.
AB  - The objective of this study was to assess the rate of nosocomial infections
      (NIs), frequency of nosocomial pathogens and antimicrobial susceptibility changes
      in a 530-bed hospital over a five-year period. Hospital-wide laboratory-based NI
      surveillance was performed prospectively between 1999 and 2003. The Centers for
      Disease Control and Prevention's definitions were used for NIs and nosocomial
      surgical site infections, and NI rates were calculated by the number of NIs per
      number of hospitalized patients on an annual basis. NI rates ranged between 1.4%
      and 2.4%. Higher rates were observed in the neurology, neurosurgery, paediatric
      and dermatology departments; the low rate of NIs overall may be due to the
      surveillance method used. The most commonly observed infections were urinary
      tract, surgical site and primary bloodstream infections, and the most frequently
      isolated pathogens were Escherichia coli, Klebsiella pneumoniae, Enterococcus
      spp. and Staphylococcus aureus. Carbapenems were the most effective agents
      against enterobacteriaceae. Meticillin resistance among S. aureus isolates was
      less than 50%, and all S. aureus and Enterococcus spp. isolates were susceptible
      to glycopeptides apart from one glycopeptide-resistant E. faecium isolate
      identified in 2003. Data obtained by the same method enabled comparison between
      years and assisted in the detection of recent changes. Antimicrobial
      susceptibility data on nosocomial pathogens provided valuable guidance for
      empirical antimicrobial therapy of NIs.

PMID- 16979793
TI  - Comparison of two alcohol-based surgical scrub solutions with an iodine-based
      scrub brush for presurgical antiseptic effectiveness in a community hospital.
AB  - The antiseptic effectiveness and acceptability of a commercial alcohol-based
      waterless (ABWL) and an alcohol-based water-aided (ABWA) scrub solution were
      compared with a brush-based iodine solution (BBIS) under conditions encountered
      in community hospital operating rooms. This randomized partially blinded study
      was based on guidelines from the American Society for Testing and Methods. The
      three scrub solutions were compared for antimicrobial efficacy, using criteria
      within the Food and Drug Administration's Tentative Final Monograph for
      Healthcare Antiseptic Products (FDA-TFM), and for participants' acceptance of the
      products. Volunteer surgical staff that worked daily in the same operating room
      for the entire duration of the study were enrolled. In total, 1126 surgical scrub
      procedures were performed over the duration of the study. Only the ABWL met all
      of the FDA-TFM criteria. The BBIS performed better than both of the alcohol-based
      solutions at the end of Day 1 (P=0.03), but the ABWL was more efficacious than
      the ABWA and the BBIS at the end of Days 2 and 5 (P=0.02 and 0.01, respectively).
      When colony-count reductions were compared over the entire duration of the study,
      there was no significant difference between the three solutions (P=0.2). The
      participants found the ABWL easiest to use (P<0.001), with the fewest adverse
      effects on skin (P=0.007), and it was their preferred product (P<0.001). Although
      both of the commercially available alcohol-based solutions may be considered as
      acceptable alternatives to the BBIS for presurgical antisepsis, the ABWL was
      found to have significantly higher user acceptability.

PMID- 16979794
TI  - Stenotrophomonas maltophilia and antibiotic use in German intensive care units:
      data from Project SARI (Surveillance of Antimicrobial Use and Antimicrobial
      Resistance in German Intensive Care Units).
AB  - Risk factors for the selection of Stenotrophomonas maltophilia were analysed by
      correlating antimicrobial use and structure parameters (e.g. hospital type) with
      the incidence density of S. maltophilia and the percentage of S. maltophilia
      isolated from 39 intensive care units (ICUs). SARI (Surveillance of Antimicrobial
      Use and Antimicrobial Resistance in German Intensive Care Units) is a prospective
      unit- and laboratory-based surveillance system that collects data on the 13 most
      important organisms responsible for nosocomial infections. The percentage of S.
      maltophilia among these organisms and the number of S. maltophilia per 1000
      patient-days were calculated. The data were subsequently correlated with
      antibiotic use density calculated in defined daily doses (DDDs) per 1000 patient
      days and structure parameters. The data covered a total of 28 266 isolates and
      431 351 DDDs. The antibiotic use density ranged from 427 to 2218, with the median
      being 1346. Over the two-year period, the median of S. maltophilia per 1000
      patient-days was 1.4 (range 0-7.6). Calculation of antibiotic use and S.
      maltophilia per 1000 patient-days showed a significant positive correlation with
      the use of carbapenems, ceftazidime, glycopeptides and fluoroquinolones, as well
      as with total antibiotic use. In the multiple logistic regression analysis,
      carbapenem use and >12 ICU beds were independently and positively associated with
      a high number of S. maltophilia per 1000 patient-days. Benchmarking data provided
      for incidence densities of S. maltophilia in ICUs revealed the heterogeneous
      situation of the burden of S. maltophilia in individual ICUs. The multi-centre
      data showed that carbapenem use and >12 ICU beds were independent risk factors
      for the isolation of S. maltophilia.

PMID- 16979795
TI  - The sensitivity of approved Ninhydrin and Biuret tests in the assessment of
      protein contamination on surgical steel as an aid to prevent iatrogenic prion
      transmission.
AB  - Regulations recommend the routine application of biochemical tests, such as the
      Ninhydrin or Biuret tests, to confirm the efficacy of hospital sterile service
      department (SSD) washer-disinfector cycles in removing proteinaceous material,
      particularly with respect to prions. The effectiveness of these methods relies on
      both the effective sampling of the instruments and the sensitivity of the tests
      employed. Two commercially available contamination assessment tests were
      evaluated for their sensitivity to ME7 brain homogenate on surgical-grade
      stainless steel surfaces. Controls were visualized by the application of
      episcopic differential interference contrast/Epi-fluorecence microscopy (EDIC/EF)
      combined with the sensitive fluorescent reagent, SYPRO Ruby, which has been shown
      previously to rapidly visualize and assess low levels of contamination on medical
      devices. The Ninhydrin test displayed a minimum level of detection observed by
      75% of volunteers (MLD(75)) of 9.25 microg [95% confidence interval (95% CI) 8.6
      10.0 microg]. The Biuret test provided better sensitivity, with a MLD(75) of 6.7
      microg (95% CI 5.4-8.2 microg). However, much lower concentrations of
      proteinaceous soiling (pg) were visualized using the EDIC/EF microscopy method.
      From these findings, it is clear that these approved colorimetric tests of
      cleaning are relatively insensitive. This investigation demonstrates how large
      amounts (up to 6.5 microg) of proteinaceous brain contamination could remain
      undetected and the instruments deemed clean using such methods. The application
      of more sensitive cleanliness evaluation methods should be applied to reduce the
      risk of iatrogenic transmission of prion disease in 'high-risk' instruments such
      as neurosurgical devices.

PMID- 16979796
TI  - Changes in the epidemiology of meticillin-resistant Staphylococcus aureus
      associated with the emergence of EMRSA-16 at a university hospital.
AB  - This study investigated the molecular epidemiology of meticillin-resistant
      Staphylococcus aureus (MRSA) in the University Hospital of the Canary Islands
      (HUC) in order to evaluate epidemiological changes over a six-year period.
      Clinical and epidemiological data were collected between May 2000 and December
      2003, and isolates were subjected to pulsed-field gel electrophoresis (PFGE),
      multi-locus sequence typing (MLST), SCCmec typing and spa typing. Since 2000, the
      rate of MRSA infections has increased at the HUC, coinciding with the emergence
      and spread of the EMRSA-16 clone (ST36-MRSA-II) and replacement of the Iberian
      clone (ST247-MRSA-I). Genotypic changes were associated with changes in the
      epidemiological profile. The mean age and proportion of patients over 60 years
      old (P=0.01) and the proportion of respiratory infections (P=0.001) increased
      significantly. Gentamicin and tetracycline susceptibility of MRSA isolates
      increased (P<0.001) following the emergence of EMRSA-16. Combining PFGE, SCCmec
      and MLST has been instrumental in understanding these changes and defining the
      clones circulating in the HUC patient population.

PMID- 16979797
TI  - Isolation and characterization of a novel thermostable non-specific lipid
      transfer protein-like antimicrobial protein from motherwort (Leonurus japonicus
      Houtt) seeds.
AB  - In screening for potent antimicrobial proteins from plant seeds, a novel heat
      stable antimicrobial protein, designated LJAMP2, was purified from seeds of the
      motherwort (Leonurus japonicus Houtt), a medicine herb, with a procedure
      involving cation exchange chromatography on a CM FF column, and reverse phase
      HPLCs on C8 column and C18 column. LJAMP2 exhibited a molecular mass of 6.2 kDa
      determined. Automated Edman degradation determined the partial N-terminal
      sequence of LJAMP2 to be NH2
      AIGCNTVASKMAPCLPYVTGKGPLGGCCGGVKGLIDAARTTPDRQAVCNCLKTLAKSYSG, which displays
      homology with plant non-specific lipid transfer proteins (nsLTPs). In vitro
      bioassays showed that LJAMP2 inhibits the growth of a variety of microbes,
      including filamentous fungi, bacteria and yeast. The growth of three
      phytopathogenic fungi, Alternaria brassicae, Botrytis maydis, and Rhizoctonia
      cerealis, are inhibited at 7.5 microM of LJAMP2, whereas Bacillus subtilis is
      about 15 microM. The IC(50) of LJAMP2 for Aspergillus niger, B. maydis, Fusarium
      oxysporum, Penicillium digitatum and Saccharomyces cerevisiae are 5.5, 6.1, 9.3,
      40.0, and 76.0 microM, respectively.

PMID- 16979798
TI  - Purification and characterization of novel antimicrobial peptides from the skin
      secretion of Hylarana guentheri.
AB  - Linear, amphipathic and cationic antimicrobial peptides have been previously
      reported from a wide range of amphibian species especially frogs of the genus
      Rana. Such antimicrobial peptides are attracting increasing attention in
      pharmacological applications because they mainly act by permeabilizing and
      disrupting the target cell or virion membranes with a low degree of resistance.
      The Guenther's frog, Hylarana guentheri, is a Chinese frog of the genus Rana that
      is widely distributed in Southern China. It is commonly the dominant amphibian
      species even where the amphibian population is declining. In this study, we
      describe the isolation, purification, structural and biological characterization
      of five novel peptides from H. guentheri frog skin secretions that possess
      antimicrobial activity, including brevinin-2GHa, brevinin-2GHb, brevinin-2GHc,
      temporin-GH and a novel antimicrobial peptide named guentherin. The cDNAs
      encoding two novel members of the brevinin-2 family, brevinin-2GHb and brevinin
      2GHc were also subsequently cloned and sequenced.

PMID- 16979799
TI  - Molecular cloning and functional characterization of a prolactin-releasing
      peptide homolog from Xenopus laevis.
AB  - Amino acid sequences for identified prolactin (PRL)-releasing peptides (PrRPs)
      were conserved in mammals (>90%) or teleost fishes (100%), but there were
      considerable differences between these classes in the sequence (<65%) as well as
      in the role of PrRP. In species other than fishes and mammals, we have identified
      frog PrRP. The cDNA encoding Xenopus laevis prepro-PrRP, which can generate
      putative PrRPs, was cloned and sequenced. Sequences for the coding region showed
      higher identity with teleost PrRPs than mammalian homologues, but suggested the
      occurrence of putative PrRPs of 20 and 31 residues as in mammals. The amino acid
      sequence of PrRP20 was only one residue different from teleost PrRP20, but shared
      70% identity with mammalian PrRP20s. In primary cultures of bullfrog (Rana
      catesbeiana) pituitary cells, Xenopus PrRPs increased prolactin concentrations in
      culture medium to 130-160% of the control, but PrRPs was much less potent than
      thyrotropin-releasing hormone (TRH) causing a three- to four-fold increase in
      prolactin concentrations. PrRP mRNA levels in the developing Xenopus brain peak
      in early prometamorphosis, different from prolactin levels. PrRP may not be a
      major prolactin-releasing factor (PRF), at least in adult frogs, as in mammals.

PMID- 16979800
TI  - Transcriptional profiling of Alzheimer blood mononuclear cells by microarray.
AB  - We evaluated pathomechanisms and systemic manifestations of Alzheimer disease
      (AD), an aging-related dementing neurodegenerative disorder, by expression
      profiling. Blood mononuclear cell (BMC) transcriptomes of sporadic AD subjects
      and aged-matched normal elderly controls (NEC) were compared using the human NIA
      microarray. Relative to the NEC samples, the Alzheimer BMC exhibited a
      significant decline in the expression of genes concerned with cytoskeletal
      maintenance, cellular trafficking, cellular stress response, redox homeostasis,
      transcription and DNA repair. We observed decreased expression of several genes
      which may impact amyloid-beta production and the processing of the microtubule
      associated protein tau. The microarray results were validated by quantitative
      real time PCR and revealed gender differences in the levels of altered gene
      expression. Our findings attest to the systemic nature of gene dys-regulation in
      sporadic AD, implicate disruption of cytoskeletal integrity, DNA repair
      mechanisms and cellular defenses in this condition, and suggest novel pathways of
      beta-amyloid deposition in this disease. BMC are highly accessible and may
      reflect molecular events germane to the neuropathophysiology of AD.

PMID- 16979801
TI  - Locking of the metacarpophalangeal joint of the thumb caused by a fracture
      fragment of the radial condyle of the metacarpal head after dorsal dislocation.
AB  - We report a case of a locked thumb metacarpophalangeal joint secondary to
      metacarpal head fracture. As fractures of the radial condyle are not readily seen
      in routine X-rays, other imaging modalities, including CT, should be considered
      if the patient complains of limited extension after hyperextension injury of the
      thumb.

PMID- 16979802
TI  - A modification to the Tupper Hand to improve intraoperative access.

PMID- 16979803
TI  - The clinical significance of the palmaris longus tendon in the pathophysiology of
      carpal tunnel syndrome.
AB  - Carpal tunnel syndrome is associated with increased intracarpal canal pressure.
      The effect of tendon loading on intracarpal canal pressures is documented in
      biomechanical studies. Palmaris longus loading in wrist extension induces the
      greatest absolute increase in intracarpal canal pressure. Despite this fact, the
      palmaris longus is not yet a proven independent risk factor for the development
      of carpal tunnel syndrome. The purpose of this prospective clinical study was to
      assess and quantify the association between the presence of a palmaris longus
      tendon and carpal tunnel syndrome. Thirty-six carpal tunnel subjects with
      bilateral disease were compared with 36 controls. Each subject was clinically
      examined for the presence of the palmaris longus tendon. The prevalence of
      palmaris longus agenesis was significantly lower in the carpal tunnel group. The
      palmaris longus tendon is a strong independent risk factor for carpal tunnel
      syndrome.

PMID- 16979804
TI  - Combined effect of copper and prolonged summer drought on soil microarthropods in
      the field.
AB  - Soil microarthropods experience a large range of natural stressors in their
      natural environment, e.g. variations in temperature and soil moisture, but also
      anthropogenic stressors such as soil pollutants. In the present study the
      combined effect of drought stress and copper pollution on microarthropods was
      investigated in a field study. We hypothesised that microarthropods in copper
      polluted soil would be more susceptible to drought than animals in control soil.
      Surprisingly, the abundance of microarthropods in autumn was positively affected
      by summer drought and copper pollution did not influence the effect of drought in
      a negative way. The stimulation was mainly seen as an increase of Acari, but also
      groups of Collembola were positively affected. We suggest that the positive
      effect of the enforced summer drought could be due to a rapid recovery, which
      further is accelerated by an increase of food resources (microbes) which have not
      been utilized during the drought.

PMID- 16979805
TI  - Phosphorus interception in floodwater of paddy field during the rice-growing
      season in TaiHu Lake Basin.
AB  - A field experiment located in TaiHu Lake Basin in China was conducted, by
      application of superphosphate or a mixture of superphosphate with manure, to
      elucidate the interception of P export during a typical rice growing season
      through 'zero-drainage water management' combined with sound irrigation, rainfall
      forecasting and field drying. P concentrations in floodwater rapidly declined
      before the first event of field drying, and subsequently tended to return to the
      background levels. Before the first field drying TPP was the predominant P form
      in floodwater on fields with no P input, DRP on plots that received
      superphosphate only, and DOP on plots treated with the mixture of superphosphate
      and manure. Thereafter TPP became the major form. No P export was found from the
      paddy fields, but a retention of 0.65kgha(-1), mainly due to soil P sorption. The
      results recommend the zero-drainage water management for full-scale areas for
      minimizing P export.

PMID- 16979806
TI  - Spatial variability of isoproturon mineralizing activity within an agricultural
      field: geostatistical analysis of simple physicochemical and microbiological soil
      parameters.
AB  - We assessed the spatial variability of isoproturon mineralization in relation to
      that of physicochemical and biological parameters in fifty soil samples regularly
      collected along a sampling grid delimited across a 0.36 ha field plot (40 x 90
      m). Only faint relationships were observed between isoproturon mineralization and
      the soil pH, microbial C biomass, and organic nitrogen. Considerable spatial
      variability was observed for six of the nine parameters tested (isoproturon
      mineralization rates, organic nitrogen, genetic structure of the microbial
      communities, soil pH, microbial biomass and equivalent humidity). The map of
      isoproturon mineralization rates distribution was similar to that of soil pH,
      microbial biomass, and organic nitrogen but different from those of structure of
      the microbial communities and equivalent humidity. Geostatistics revealed that
      the spatial heterogeneity in the rate of degradation of isoproturon corresponded
      to that of soil pH and microbial biomass.

PMID- 16979807
TI  - Role of alpha-tocopherol on antioxidant status in liver, lung and kidney of PCB
      exposed male albino rats.
AB  - Polychlorinated biphenyls (PCB) are widespread, lipophilic environmental
      pollutants which have been identified as contaminants in almost every component
      of the global ecosystem including fish, wildlife, and human adipose tissue,
      breast milk, and serum. Several studies have shown that PCBs can cause oxidative
      damage to biomolecules, in the form of lipid peroxidation, modulation of
      antioxidant enzymes, and oxidative stress. In the present study, we have sought
      to investigate the effects of alpha-tocopherol (vitamin E) on antioxidant status
      of PCB-induced toxicity in male Wistar rats. The protective effect of alpha
      tocopherol (50mg/kg body weight/day) was tested in PCB-induced toxicity in rat
      liver, lung, and kidney. We report here that the oral supplementation of alpha
      tocopherol was found to maintain the cellular redox status by maintaining the
      activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione
      reductase accompanied with glutathione and vitamin E levels and down regulation
      in the levels of lipid peroxides, hydroxyl radical and hydrogen peroxides
      generation in PCB treated rats. Therefore, our present study demonstrates the PCB
      induced deficits in antioxidant enzyme activities and increase in reactive oxygen
      species and lipid peroxidation levels in liver, kidney, and lung which can be
      overcome through simultaneous supplementation with alpha-tocopherol.

PMID- 16979808
TI  - Development of next generation medical countermeasures to nerve agent poisoning.
AB  - Medical countermeasures provide a key role in the UK integrated approach to
      chemical defence and are aimed at preventing or mitigating the effects of
      exposure to nerve agents. It is UK policy that medical countermeasures will be
      licensed products. Demonstration of efficacy relies on extrapolation of animal
      derived data to man which means that species selection is extremely important.
      For the foreseeable future it is likely that a combination of pretreatment and
      therapy will be required to provide protection against nerve agent poisoning.
      There is a longer-term aspiration to develop a post poisoning-therapy which would
      reduce the reliance on pretreatment, prevent or mitigate the effects of exposure
      to all nerve agents and decrease the requirement for three autoinjectors.
      Immediate therapy comprising physostigmine (0.2mg/kg), hyoscine hydrobromide
      (4mg/kg) and HI-6 (93.6mg/kg) protected all animals against the lethal effects of
      a supralethal dose of GD, when given 1min after nerve agent poisoning in the
      absence of any pretreatment. In contrast when hyoscine hydrobromide was replaced
      with hyoscine methyl nitrate most of the animals died within 24h, whereas when an
      equal mixture of hyoscine hydrobromide and hyoscine methyl nitrate was used all
      the animals survived. None of these animals had an intussusception. It would not
      be possible to deliver these doses of HI-6 to a human from a single autoinjector
      device. Recent studies have shown that a lower dose of HI-6 (7mg/kg) which can be
      delivered via an autoinjector, in combination with physostigmine and hyoscine
      hydrobromide provides good protection against the lethal effects of a supralethal
      dose of GD. A number of animals died between 6 and 24h and had an
      intussusception. The surviving animals did not begin to regain weight until 48h
      after poisoning. In contrast when a mixture of hyoscine hydrobromide and hyoscine
      methyl nitrate was used, one animal died within 15min, the other animals all
      survived, regained weight from 24h and did not have an intussusception. These
      studies will now be extended to include other agents and will be taken forward to
      studies in non-human primates where the incidence of intussusception will be
      closely monitored.

PMID- 16979809
TI  - Oral administration of Cr(VI) induced oxidative stress, DNA damage and apoptotic
      cell death in mice.
AB  - Potassium dichromate (Cr(VI)) was given orally to Swiss mice for 1 and 5 days
      with the dose of 25, 50 and 100 mg/kg body weight per day, respectively.
      Oxidative stress including the level of reactive oxygen species (ROS), the extent
      of lipid peroxidation and the activity of antioxidant enzymes in liver and kidney
      was determined. DNA damage in peripheral blood lymphocytes was determined by
      single-cell gel electrophoresis (comet assay). Apoptotic cell death in liver was
      detected using transmission electron microscopy and TUNEL assay. The results
      indicated that administration of Cr(VI) had caused a significant increase of ROS
      level in liver both after 1 and 5 days of exposure, accompanied with a dose
      dependent decrease in superoxide dismutase (SOD) and catalase (CAT) activities.
      The malondialdehyde (MDA) content in liver was not changed as compared to the
      control animals. In contrast to the liver, no significant changes were observed
      in kidney on ROS, SOD, CAT and MDA as compared to the control animals. Dose- and
      time-dependent effects were observed on DNA damage after 1 and 5 days treatment.
      Significant difference was observed on the number of TUNEL positive liver cells
      between the control and Cr(VI) treatment groups. The apoptotic cells were also
      identified by characteristic ultrastructural features. The results obtained from
      the present study showed that Cr(VI) given orally to mice could induce dose- and
      time-dependent effects on DNA damage, hepatic oxidative stress and hepatocytes
      apoptosis. No significant oxidative stress observed in kidney in the study may
      suggest that the way of Cr(VI) exposure is an important factor affecting its
      toxicity.

PMID- 16979810
TI  - Alterations of energy metabolism and glutathione levels of HL-60 cells induced by
      methacrylates present in composite resins.
AB  - OBJECTIVES: Methacrylic compounds such as 2-hydroxyethyl methacrylate (HEMA),
      triethylene glycol dimethacrylate (TEGDMA) and bisphenol A glycerolate (1
      glycerol/phenol) dimethacrylate (Bis-GMA) are largely present in auto- or
      photopolymerizable composite resins. Since the polymerization reaction is never
      complete, these molecules are released into the oral cavity tissues and
      biological fluids where they could cause local adverse effects. The aim of this
      work was to verify the hypothesis that the biological effects of HEMA, TEGDMA and
      Bis-GMA - at a non-cytotoxic concentration - depend on the interaction with
      mitochondria and exert consequent alterations of energy metabolism, GSH levels
      and the related pathways in human promyelocytic cell line (HL-60). METHODS: The
      biological effects of methacrylic monomers were determined by analyzing the
      following parameters: GSH concentration, glucose-6-phosphate dehydrogenase
      (G6PDH) and glutathione reductase (GR) activity, oxygen and glucose consumption
      and lactate production along with cell differentiation and proliferation.
      RESULTS: All monomers induced both cellular differentiation and decrease in
      oxygen consumption. Cells treated with TEGDMA and Bis-GMA showed a significant
      enhancement of glucose consumption and lactate production. TEGDMA and HEMA
      induced GSH depletion stimulating G6PDH and GR activity. CONCLUSIONS: All the
      monomers under study affect the metabolism of HL-60 cells and show
      differentiating activity. Since alterations in cellular metabolism occurred at
      compound concentrations well below cytotoxic levels, the changes in energy
      metabolism and glutathione redox balance could be considered as potential
      mechanisms for inducing clinical and sub-clinical adverse effects and thus
      providing useful parameters when testing biocompatibility of dental materials.

PMID- 16979811
TI  - Patterns of salivary cortisol secretion in pregnancy and implications for
      assessment protocols.
AB  - Cortisol is used in research as a biomarker of psychological stress. Logistical
      considerations argue for collecting as few samples as possible, balanced against
      diurnal rhythms and intra-individual variations. 100 pregnant women gave five
      saliva samples a day for 3 days, at waking, 30 min after waking, and 11:00 a.m.,
      5:00 p.m., and 9:00 p.m. Timing of collection was confirmed by monitors. Another
      sample was taken during a clinic visit. Using the 15 measures as the gold
      standard, correlations and mean area under the curve (AUC) were compared with
      subsets and the single clinic sample to evaluate alternate collection protocols.
      Five samples in 1 day, or protocols involving morning and night samples, had the
      highest correlations with mean AUC (correlation coefficient ranging from 0.82 to
      0.88). Standardizing the clinic measurement to a single time of day did not
      substantially improve correlations with mean AUC. Correlations with measures of
      reported stress were also not strong.

PMID- 16979812
TI  - Serum levels of 3alpha-androstanediol glucuronide in young women with polycystic
      ovary syndrome, idiopathic hirsutism and in normal subjects.
AB  - OBJECTIVE: The study objective was to assess the role of 3alpha-androstanediol
      glucuronide (3alpha-diolG) as the marker of peripheral androgen action in the
      young women with hirsutism diagnosed as polycystic ovary syndrome (PCOS), in
      patients with idiopathic hirsutism (IH) and in normal non-hirsute women. STUDY
      DESIGN: Fifty-nine young women with mean age 21.90+/-3.52 years suffered from
      hirsutism were included in the study. Among these 59 hirsute women 31 women with
      mean age 21.60+/-3.56 years were diagnosed as PCOS and 28 women with mean age
      22.20+/-3.59 years were classified as idiopathic hirsutism patients. Twenty-seven
      normal women, age-matched (mean age 22.60+/-2.90 years), without signs of
      hirsutism and with normal menstrual cycle served as control for this study. Serum
      was collected from women with hirsutism (due to PCOS or idiopathic hirsutism) and
      from non-hirsute women. Serum levels of 3alpha-androstanediol glucuronide (3alpha
      diolG), main androgens such as: testosterone, free testosterone,
      dehydroepiandrosterone (DHEAS) and also others hormones such as follicle
      stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and sex
      hormone-binding globuline (SHBG) were measured using radioimmunoassay (RIA)
      method in the study and control group. Hirutism was assessed using modified
      Ferriman-Gallwey method. Serum 3alpha-diolG levels in PCOS women were
      significantly higher than in controls. RESULTS: There were no significant
      differences between serum 3alpha-diolG levels in PCOS group and IH group.
      Similarly, there were significant differences between serum 3alpha-diolG levels
      in IH group and control subjects. CONCLUSION: We conclude that 3alpha-diolG is
      not useful as the marker for peripheral androgen metabolism and for
      differentiation between idiopathic hirsutism and PCO-related hirsutism.

PMID- 16979813
TI  - Photophysics of ANS. V. Decay modes of ANS in proteins: the IFABP-ANS complex.
AB  - The fluorescence properties of ANS as bound to proteins are treated. Several
      points of view concerning the origin of these properties are reviewed and
      synthesized into one framework. On proteins where the quantum yield (QY) is
      appreciable, as in organic solvents, the preferred conformation of ANS is often
      with the phenyl ring nearly (65 degrees -85 degrees ) orthogonal to the
      naphthalene. The major consequence of this geometry is water exclusion from the
      critical zone of ANS at which the largest amount of solvent dipolar relaxation
      originates. This, in turn, leads to a depression of the rate of electron transfer
      to the surroundings, together with other effects, as noted in the literature and
      in our lab. Alternative quenching pathways for ANS on the protein vs in water are
      also elucidated.

PMID- 16979814
TI  - Combining testosterone and PDE5 inhibitors in erectile dysfunction: basic
      rationale and clinical evidences.
AB  - INTRODUCTION: Erectile dysfunction (ED) and decline of testosterone levels are
      frequently observed with age and also in illnesses with a common basis of
      endothelial damage. OBJECTIVES: To review molecular mechanisms underlying
      androgen action upon its receptor and phosphodiesterase type 5 (PDE5) expression
      and regulation by testosterone in cavernous tissue and their clinical implication
      in the treatment of ED refractory to PDE5 inhibitors (PDE5-Is). METHODS: From
      January 2003 to May 2006 [corrected] we performed an extensive, unsystematic
      MEDLINE literature search reviewing relevant data on basic and clinical studies
      regarding the efficacy of combination therapies. RESULTS: Most trials using
      testosterone alone for treatment of ED in hypogonadal men suffer from
      methodologic problems and report inconsistent results, but overall the trials
      suggest that testosterone is superior to placebo. Orally effective PDE5-Is, such
      as sildenafil, tadalafil, or vardenafil, may be ineffective depending on the
      demonstration of testosterone regulation of PDE5 expression in human corpus
      cavernous, and their efficacy may be enhanced by testosterone adjunction whenever
      necessary. CONCLUSIONS: Screening for hypogonadism in all men with ED is
      necessary to identify men with severe hypogonadism and some cases of mild to
      moderate hypogonadism, who may benefit from testosterone treatment.
      Identification of threshold values for testosterone supplementation to
      appropriately benefit from PDE5-Is failure may improve clinical management of
      unresponsive patients with minimization of unwanted effects.

PMID- 16979815
TI  - Biosorption of cadmium by various types of dried sludge: an equilibrium study and
      investigation of mechanisms.
AB  - Batch equilibrium sorption experiments were used for screening for cost-effective
      four types of sludge, which were DWS (drinking water treatment plant sludge), LLS
      (landfill leachate sludge), ADSS (anaerobically digested sewage sludge), and SS
      (sewage sludge). SS removed cadmium most efficiently from aqueous solution (0.38
      mmol/g), and showed the highest desorption efficiency (26.3%). Only the SS can be
      fitted by Langmuir isotherm model (r2 = 0.996). The FT-IR spectra of SS and
      cadmium loaded SS indicated that carboxyl groups were major binding sites of
      cadmium binding sites. In kinetic experiment, it was found that the uptake of the
      metal by the SS was accompanied with proton release, indicating that the metal
      binding occurs via an ion exchange as well as by electrostatic interaction
      between carboxylate groups and cadmium ions. This sorbent may have a potential
      for use as high-value biosorbent of heavy metals and it deserves further
      investigations into the details of practical application, for example on the
      development of desorption methods and on sorption process optimization.

PMID- 16979816
TI  - Stabilization/solidification of munition destruction waste by asphalt emulsion.
AB  - Destruction of discarded military munitions in an explosion chamber produces two
      fractions of hazardous solid waste. The first one is scrap waste that remains in
      the chamber after explosion; the second one is fine dust waste, which is trapped
      on filters of gas products that are exhausted from the chamber after explosion.
      The technique of stabilization/solidification of the scrap waste by asphalt
      emulsion is described in this paper. The technique consists of simple mixing of
      the waste with anionic asphalt emulsion, or two-step mixing of the waste with
      cationic asphalt emulsion. These techniques are easy to use and the stabilized
      scrap waste proves low leachability of contained heavy metals assessed by TCLP
      test. Hence, it is possible to landfill the scrap waste stabilized by asphalt
      emulsion. If the dust waste, which has large specific surface, is stabilized by
      asphalt emulsion, it is not fully encapsulated; the results of the leaching tests
      do not meet the regulatory levels. However, the dust waste solidified by asphalt
      emulsion can be deposited into an asphalted disposal site of the landfill. The
      asphalt walls of the disposal site represent an efficient secondary barrier
      against pollutant release.

PMID- 16979817
TI  - Water chemistry and ecotoxicity of an acid mine drainage-affected stream in
      subtropical China during a major flood event.
AB  - Field and laboratory work was carried out to investigate the chemistry and
      ecotoxicity of stream water affected by acid mine drainage in a tributary
      catchment of the Pearl River in subtropical China during a major flood that
      corresponded to a return period of 100 years. The results indicate that stream
      water was affected by acid mine drainage from the Dabaoshan mine at least to a
      distance of 25 km downstream of the mine water discharge point. It appears that
      H(+) generated from sulfide oxidation in the waste rock dumps was readily
      available for exporting. The amount of H(+) being discharged into the receiving
      stream depended on the volume of out-flowing waters. However, there was a lag
      time for the discharges of the metals. This may be attributed to the slower
      release of metals, relative to H(+), because it might take more time for the
      dissolution of heavy metal-bearing compounds, particularly the sparsely soluble
      jarosites. Fe, Zn and Al were the major metals of potential toxicity contained in
      the AMD-affected stream water, followed by Mn, Cu, Pb, As, Cd and Ni. The
      concentrations of these metals in the water decreased rapidly down the stream.
      This corresponds with an increase in the concentrations of reactive heavy metal
      fractions in benthic mud down the stream, reflecting the precipitation of heavy
      metal compounds with increasing pH and their subsequent deposition in the
      streambed. Toxicity tests show that the AMD-affected stream water at 3.5 km
      downstream of the discharge point was highly toxic to the test organism. At 25 km
      downstream of the discharge point where stream water pH was as high as 5.75,
      marked toxic responses of the test organism were still observed.

PMID- 16979819
TI  - Ammonium exchange in aqueous solution using Chinese natural clinoptilolite and
      modified zeolite.
AB  - In this study, the Chinese natural clinoptilolite (sample 1) was fused with
      sodium hydroxide prior to hydrothermal reaction, and it was transformed to
      modified zeolite Na-Y (sample 2). The uptake of ammonium ion from aqueous
      solutions in the concentration range 50-250 mg NH(4)(+)/l on to the two samples
      was compared and the equilibrium isotherms have been got. The influence of other
      cations present in water upon the ammonia uptake was also determined. The cations
      studied were potassium, calcium and magnesium. In all cases the anionic
      counterion present was chloride. The results showed that sample 2 exhibited much
      higher uptake capacity compared with sample 1. At the initial concentration of
      250 mg NH(4)(+)/l, the ammonium ion uptake value of sample 2 was 19.29 mg
      NH(4)(+)g(-1) adsorbent, while sample 1 was only 10.49 mg NH(4)(+)g(-1)
      adsorbent. For the natural clinoptilolite, the effect of the metal ions suggested
      an order of preference K(+)>Ca(2+)>Mg(2+). These contrasted with the modified
      zeolite, where the order appeared to be Mg(2+)>Ca(2+)>K(+).

PMID- 16979820
TI  - The influences on leachate from landfill of incineration residuals by acid
      precipitation.
AB  - Incineration of municipal solid wastes (MSW) is the main method of waste
      management in Taiwan. Although the incineration of MSW processes the solid wastes
      at 850-950 degrees C and destroys most of the organics, the content of
      incineration ashes is still a problem for landfill. Moreover, acid precipitation
      is much worse than before in Taiwan, especially in the northern areas. For
      instance, the occurrence probabilities of acid precipitation measured from 1991
      to 1998 in Taipei increase from 73% to 85%. Therefore, it is more important to
      get a series of data that will help explore the influence of acid precipitation
      during disposal on characterization of pollutants than to analyze the ash
      properties after the incinerators have been constructed and regularly used. In
      this investigation, the disposal site of incineration ashes is simulated in
      laboratory by test columns. An irrigation experiment is taken to simulate the
      acid precipitation at room temperature. In order to explore the exact influence
      on leachate quality of the main chemical composition of acid precipitation,
      columns are migrated with different concentrations of sulfate in acid
      precipitation. This investigation showed that the sulfate concentration of acid
      precipitation has an increasing effect on the accumulative release of heavy
      metals, such as Zn, Pb and Cu, from leachate. The sulfate concentration of acid
      precipitation, however, will not influence the trend of chemical oxygen demand
      (COD), biochemical oxygen demand (BOD(5)) and total organic carbon (TOC) in the
      leachate release.

PMID- 16979821
TI  - PPARD haplotype influences cholesterol metabolism but is no risk factor of
      Alzheimer's disease.
AB  - Cholesterol metabolism is involved in Alzheimer's disease (AD) pathogenesis:
      increased cholesterol blood levels are detected in AD patients, and treatment
      with statins reduces the risk of AD. The peroxisome proliferator-activated
      receptor delta protein (PPARdelta), is a member of the steroid hormone super
      family of ligand-inducible transcription factors, and is of major relevance in
      lipid and cholesterol metabolism. We investigated three frequent polymorphisms
      located in exons 4 (rs2016520) and 9 (rs3734254 and rs9794) of the PPARdelta gene
      (PPARD) for their putative influence on the risk of AD and on plasma levels of
      cholesterol, 24S-hydroxycholesterol and 27-hydroxycholesterol. The study
      population consisted of 167 AD patients (mean age: 74.27+/-9.37 years; female
      78.6%) and 194 controls (mean age: 73.26+/-8.37 years; female 57.2%). Haplotype
      analysis was perfomed, however, we did not find PPARD haplotypes to influence the
      risk of AD. In contrast to these results, a two marker haplotype consisting of
      rs2016520 and rs9794 in AD patients showed a significant effect on the relative
      plasma levels of 24S-hydroxycholesterol (carriers: 32.1+/-2.8ng/mg; non-carriers:
      40.3+/-1.4ng/mg; p=0.016) and 27-hydroxycholesterol (carriers: 40.8+/-7.7ng/mg;
      non-carriers: 58.6+/-2.3ng/mg; p=0.002) but not in non-demented controls. Our
      results suggest that PPARD haplotypes might influence levels of cholesterol
      metabolites in AD patients, but act not as risk factors of AD.

PMID- 16979822
TI  - Quantification and thickness correction of EFTEM phosphorus maps.
AB  - We describe a method for correcting plural inelastic scattering effects in
      elemental maps that are acquired in the energy filtering transmission electron
      microscope (EFTEM) using just two energy windows, one above and one below a core
      edge in the electron energy loss spectrum (EELS). The technique is demonstrated
      for mapping low concentrations of phosphorus in biological samples. First, the
      single-scattering EELS distributions are obtained from specimens of pure carbon
      and plastic embedding material. Then, spectra are calculated for different
      specimen thicknesses t, expressed in units of the inelastic mean free path
      lambda. In this way, standard curves are generated for the ratio k0 of post-edge
      to pre-edge intensities at the phosphorus L2,3 excitation energy, as a function
      of relative specimen thickness t/lambda. Thickness effects in a two-window
      phosphorus map are corrected by successive acquisition of zero-loss and
      unfiltered images, from which it is possible to determine a t/lambda image and
      hence a background k0-ratio image. Knowledge of the thickness-dependent k0-ratio
      at each pixel thus enables a more accurate determination of the phosphorus
      distribution in the specimen. Systematic and statistical errors are calculated as
      a function of specimen thickness, and elemental maps are quantified in terms of
      the number of phosphorus atoms per pixel. Further analysis of the k0-curve shows
      that the EFTEM can be used to obtain reliable two-window phosphorus maps from
      specimens that are considerably thicker than previously possible.

PMID- 16979823
TI  - Ovine echinococcosis I. Immunological diagnosis by enzyme immunoassay.
AB  - Immunodiagnosis in sheep presents problems of sensitivity and specificity,
      limiting its applicability in surveillance systems. The objective of this study
      was to develop a sensitive, specific and accessible technique for diagnosing
      cystic echinococcosis in naturally infected sheep and to evaluate the validity of
      necropsy as a reference test. A total of 247 sheep were studied at
      slaughterhouses, confirming the parasitological diagnosis with histology. Serum
      was processed with enzyme immunoassay (EIA) using three antigen preparations:
      total hydatid liquid (LHT), purified fraction of LHT (S2B) and purified
      lipoprotein (B). Western Blot (WB) was used as a control. EIA proved effective
      for differentiating Echinococcus granulosus from larval stage of Taenia
      hydatigena and intestinal cestodes in all three antigen preparations. Serums from
      macroscopically negative sheep were reactive to EIA and positive with WB. In the
      whole flock, sensitivity was 89.2% for LHT, 80.0% for S2B and 86.4% for B.
      Sensitivity in lambs was 78.6% for LHT, 75.0% for S2B and 64.3% for B.
      Macroscopic diagnosis at the time of slaughter was found to have limitations as a
      reference test for immunodiagnosis of cystic equinococcosis in sheep, so it was
      necessary to include histology and WB as reference tests. LHT was the antigen
      preparation of greatest value and EIA proved to be a sensitive and specific
      technique, adequate for surveillance systems and for evaluating control
      programmes.

PMID- 16979824
TI  - Effects of immunization of Pelibuey lambs with Oestrus ovis digestive tract
      protein extracts on larval establishment and development.
AB  - Larval midgut proteins of hematophagous parasites contain strong antigens that
      can be used for host immunization. This concept has been applied for immunization
      of Pelibuey sheep against Oestrus ovis L. (Diptera: Oestridae). The aim of this
      study was to examine the effect of immunization on larval establishment (LE) and
      development. Immunized lambs (I, n = 6) received two injections of crude gut
      membrane protein extracts (GMPE) from third instar larvae with Freund's
      incomplete adjuvant (FIA) on days 0 (Day of first immunization) and 21 (0.4 and
      0.45 mg GMPE/lamb, respectively). The control group (C, n = 5) received
      physiological saline with FIA. Lambs were challenged with first instars on Day 29
      (20 larvae) and Day 43 (25 larvae). Blood samples were collected biweekly and IgG
      titers were analyzed by ELISA. All lambs were slaughtered on Day 90 and number of
      larvae recovered, larval stage and larval weight were recorded at necropsy. No
      significant effect of immunization on LE (C = 28.9%; I = 31.0% P > 0.05) was
      observed. Antibody titers were higher in the immunized group on Day 28 (P <
      0.05), but subsequently similar in both groups. Larval physiological age and
      weight were also significantly (P < 0.05) affected by immunization. Immunization
      of Pelibuey lambs with GMPE did not affect LE but did delay O. ovis larval
      development.

PMID- 16979825
TI  - Evaluation of transformation growth factor beta1, interleukin-10, and interferon
      gamma in male symptomatic and asymptomatic dogs naturally infected by Leishmania
      (Leishmania) chagasi.
AB  - The aims of this study were to evaluate the immunomodulatory role of TGF-beta1,
      IL-10, and INF-gamma in spleen and liver extracts and supernatant cultures of
      white spleen cells from male symptomatic and asymptomatic dogs, naturally
      infected by Leishmania (Leishmania) chagasi. Thirty dogs from Aracatuba, Sao
      Paulo, Brazil, an endemic leishmaniosis area, were selected by positive ELISA
      serological reaction for Leishmania sp. and divided into two groups: asymptomatic
      (n=15) and symptomatic (n=15) consisting of animals with at least three
      characteristic signs (fever, dermatitis, lymphoadenopathy, onychogryphosis,
      weight loss, cachexia, locomotion problems, conjunctivitis, epistaxis,
      hepatosplenomegaly, edema, and apathy). After euthanasia, spleen and liver
      fragments were collected for ex vivo quantification of TGF-beta1, IL-10, and INF
      gamma. Naturally active in vitro produced TGF-beta1 was also evaluated in spleen
      cell culture supernatant. Spleen and liver extract of asymptomatic dogs had
      higher mean TGF-beta1 levels than symptomatic dogs. High concentrations of IL-10
      were found in spleen, and mainly in liver extract of both groups. Higher INF
      gamma concentrations were found in spleen extracts of symptomatic dogs, and in
      liver extracts of asymptomatic dogs. Extract of this cytokine was lower in spleen
      extract. Although INF-gamma is being produced in canine infection, mean levels of
      TGF-beta1 and IL-10 from spleen and liver extracts were quantitatively much
      higher; suggesting that immune response in both asymptomatic and symptomatic dogs
      was predominantly type Th2.

PMID- 16979826
TI  - Is the expression of kinin B(1) receptor related to intrahepatic vascular
      response?
AB  - Bradykinin elicits an intrahepatic vascular response (IHVR) mediated by the
      constitutive B(2) receptor (B(2)R). The biological effects of kinins may also be
      mediated by the inducible B(1) receptor (B(1)R). AIM: To verify if the hepatic
      B(1)R expression modulates IHVR to kinins. METHOD: We evaluated the ability of
      bradykinin and B(1)R agonists to elicit an IHVR in normal rats and in those
      submitted to acute or chronic inflammatory stimuli, fibrosis, cirrhosis, or
      hepatic regeneration. RESULTS: Bradykinin-induced IHVR was similar in all groups.
      B(1)R agonists did not elicit in any of them either a hypertensive or a
      hypotensive response. B(1) receptor induction was observed in all experimental
      groups (Western blot), except for the acute inflammatory group. CONCLUSION: B(1)R
      hepatic expression did not modulate IHVR to kinins.

PMID- 16979827
TI  - Contribution of peripheral 5-HT2A or 5-HT3 receptors to Fos expression in the
      trigeminal spinal nucleus produced by acute injury to the masseter muscle during
      persistent temporomandibular joint inflammation in rats.
AB  - We investigated the contribution of peripheral 5-HT2A or 5-HT3 receptors to Fos
      expression in the trigeminal spinal nucleus (VSP) following acute masseter muscle
      injury in male rats with or without temporomandibular joint (TMJ) inflammation
      persisting for 7 days. TMJ inflammation was evoked by an injection of complete
      Freund's adjuvant (CFA). Two hours after formalin injection into the masseter
      muscle produced Fos-like immunoreactivity (Fos-LI) in several regions of the VSP
      and upper cervical spinal cord (C2), such as ventrolateral (vl) area of the
      trigeminal subnucleus caudalis (Vc)/subnucleus interpolaris (Vi) transition (vl
      Vi/Vc), paratrigeminal nucleus (dPa5), middle portion of the Vc (mid-Vc) and
      Vc/C2 transition (Vc/C2) regions in both groups. Significant increases in the
      number of Fos-LI were observed in these areas in CFA group compared with non-CFA
      group. TMJ inflammation alone did not induce a significant level of Fos-LI in the
      VSP. In order to assess the effect of antagonizing 5-HT2A or 5-HT3 receptors on
      formalin-induced Fos-LI, rats were pre-treated with local (masseter muscle)
      administration of ketanserin or tropisetron (0.01, 0.1 mg/rat) 20 min prior to
      formalin injection. In CFA group, these antagonists given locally reduced the Fos
      LI response in the laminae I-II at the mid-Vc and Vc/C2 regions. These
      antagonists reduced the Fos-LI response in the dPa5, but not in the vl-Vi/Vc
      region. The Fos-LI response was not affected by i.v. administration of ketanserin
      (0.01, 0.1 mg/rat) or tropisetron (0.01 mg/rat). In non-CFA group, these
      antagonists given locally did not reduce the Fos-LI response. These results
      suggest that peripheral 5-HT2A and 5-HT3 receptors contribute to nociceptive
      processing in the masseter muscle in TMJ inflammatory conditions.

PMID- 16979828
TI  - Neuronal responses to a delayed-response delayed-reward go/nogo task in the
      monkey posterior insular cortex.
AB  - Anatomical connections of the insular cortex suggest its involvement in
      cognition, emotion, memory, and behavioral manifestation. However, there have
      been few neurophysiological studies on the insular cortex in primates, in
      relation to such higher cognitive functions. In the present study, neural
      activity was recorded from the monkey insular cortex during performance of a
      delayed-response delayed-reward go/nogo task. In this task, visual stimuli
      indicating go or nogo responses associated with reward (reward trials) and with
      no reward (no-reward trials) were presented after eye fixation. In the reward
      trials, the monkey was required to release a button during presentation of the
      2nd visual stimuli after a delay period (delay 1). Then, a juice reward was
      delivered after another delay (delay 2). The results indicated that the neurons
      responding in each epoch of the task were topographically localized within the
      insular cortex, consistent with the previous anatomical studies indicating
      topographical distributions of afferent inputs from other subcortical and
      cortical sensory areas. Furthermore, some insular neurons 1) nonspecifically
      responded to the visual cues and during fixation; 2) responded to the visual cues
      predicting reward and during the delay period before reward delivery; 3)
      responded differentially in go/nogo trials during the delay 2; and 4) responded
      around button manipulation. The observed patterns of insular-neuron responses and
      the correspondence of their topographical localization to those in previous
      anatomical studies suggest that the insular cortex is involved in attention- and
      reward-related functions and might monitor and integrate activities of other
      brain regions during cognition and behavioral manifestation.

PMID- 16979829
TI  - Effects of short-term and chronic olanzapine treatment on immediate early gene
      protein and tyrosine hydroxylase immunoreactivity in the rat locus coeruleus and
      medial prefrontal cortex.
AB  - Atypical antipsychotic drugs, such as olanzapine, have been reported to activate
      the locus coeruleus (LC) and lead to acute expression of the Fos-like immediate
      early gene (IEG) protein in the LC and medial prefrontal cortex (mPFC). Stimuli
      that activate the LC have been reported to increase expression of tyrosine
      hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. However,
      the effects of chronic treatment with olanzapine on IEG expression and the dose
      dependence of the effects of olanzapine on IEG and TH expression are not known.
      Thus, we examined Fos-like, c-Jun, activating transcription factor 2 (ATF-2),
      early growth response 1 (Egr-1), early growth response 2 (Egr-2), and TH
      immunoreactivity expression in the LC and mPFC in rats receiving 2, 4, 8, or 15
      mg/kg/day olanzapine by s.c. osmotic minipump for 4 h, 1 week, 2 weeks, or 4
      weeks. ATF-2 expression was up-regulated at all treatment durations, while Egr-1
      and Egr-2 were down-regulated in both the LC and mPFC. Fos-like expression was up
      regulated through 2 weeks, but not 4 weeks, in both the LC and mPFC. C-Jun
      expression was up-regulated for 4 weeks in the LC and for 2 weeks, but not 4
      weeks, in the mPFC. At all doses, there were rapid and sustained increases in TH
      immunoreactivity in the LC, but only delayed increases in the mPFC. These data
      indicate that olanzapine has rapid effects on IEG in the LC and mPFC, many of
      which are sustained through four weeks of treatment. Further, these data indicate
      that the delayed increase in TH expression in the mPFC parallels, and may play an
      important role in, the increased efficacy of olanzapine that emerges over time in
      humans.

PMID- 16979830
TI  - Differential expression of group I metabotropic glutamate receptors in human
      motoneurons at low and high risk of degeneration in amyotrophic lateral
      sclerosis.
AB  - Glutamate excitotoxicity has been suggested to play a role in amyotrophic lateral
      sclerosis, since overstimulation of post-synaptic glutamate receptors by
      accumulated extracellular glutamate leads to motoneuron cell death. It is however
      unclear as to why some groups of motoneurons degenerate in this disease while
      other groups remain relatively intact even during terminal stages of the disease.
      Our previous studies in the rat showed differential expression of group I
      metabotropic glutamate receptors in motoneurons at low and high risk of
      degeneration in amyotrophic lateral sclerosis. Here we have extended this study
      to normal human brains. In situ hybridization showed that transcripts of both
      metabotropic glutamate receptor (mGluR) 1 and mGluR5 were expressed in
      motoneurons in both the resistant motor nucleus III and the vulnerable motor
      nucleus XII. Immunolabeling of mGluR1alpha and mGluR5 was found in both
      motoneurons and glia-like cells in all the motor nuclei and the ventral horn of
      the cervical spinal cord studied. Quantitative analysis of optical density
      measurements showed higher levels of mGluR1alpha protein expression but lower
      levels of mGluR5 protein expression in the vulnerable motoneuron pool (VII, XII
      and spinal cord) than in the resistant motoneuron pool (III, IV and VI). This
      differential expression of group I metabotropic glutamate receptor proteins
      within vulnerable motoneuron pools may predispose these neurons to degeneration
      as seen in amyotrophic lateral sclerosis.

PMID- 16979831
TI  - Radioimmunotherapy of human colon cancer xenografts by using 131I labeled-CAb1
      F(ab')2.
AB  - PURPOSE: Therapeutic efficacy, suitable dose, and administration times of 131I
      CAb1 F(ab')2, a new monoclonal antibody therapeutics specifically directed
      against a cell surface-associated glycoprotein of colon cancer, were investigated
      in this article. METHODS AND MATERIALS: In human colon cancer xenografts, 131I
      CAb1 F(ab')2 at the dose of 125 muCi, 375 muCi, and 1125 muCi were administrated
      intraperitoneally on Days 6 and 18 after implantation of HR8348 cells with CAb1
      high reactivity. Survival time and tumor growth inhibition rate were used to
      evaluate the efficacy and safety of 131I-CAb1 F(ab')2 in treatment of colon
      cancer xenografts. RESULTS: Treatment of 125, 375, and 1125 muCi 131I-CAb1
      F(ab')2 did not significantly decrease the mean survival time of nude mice when
      compared with nontreated groups (p = 0.276, 0.865, 0.582, respectively).
      Moreover, the mean survival times of nude mice receiving 375 muCi and 1125 muCi
      131I-CAb1 F(ab')2 were significantly longer than that of 5-FU-treated groups (p =
      0.018 and 0.042). Tumor growth inhibition rates of the first therapy were 35.67%
      and 41.37%, with corresponding 131I-labeled antibody dosage of 375 muCi and 1125
      muCi. After single attack dosage, second reinforcement therapy may rise efficacy
      significantly. Tumor growth inhibition rates of 125 muCi, 375 muCi, and 1125 muCi
      131I-labeled antibody on Day 20 posttherapy were 42.65%, 56.56%, and 84.41%,
      respectively. Histopathology examination revealed that tissue necrosis of various
      degrees was found in 131I-CAb1 F(ab')2-treated groups. CONCLUSION: 131I-CAb1
      F(ab')2 is safe and effective for colon cancer. It may be a novel and potentially
      adjuvant therapeutics for colon cancer.

PMID- 16979832
TI  - A prognostic scoring system for locoregional control in nasopharyngeal carcinoma
      following conformal radiotherapy.
AB  - PURPOSE: This study established a prognostic scoring system for nasopharyngeal
      carcinoma (NPC), which estimates the probability of locoregional (LR) control
      following definitive conformal radiotherapy. METHODS AND MATERIALS: Patients with
      nondisseminated NPC at initial presentation (n = 630) were enrolled in this
      study. All patients had magnetic resonance imaging of the head and neck and were
      treated with conformal radiotherapy. Among them, 93% had concurrent chemotherapy,
      and 76% had postradiation chemotherapy. The extent of the primary tumor, age at
      diagnosis, primary tumor size, tumor and nodal classification, histology, and
      serum lactate dehydrogenase (LDH) level before treatment were included in the
      analysis for building a prognostic scoring system. The end point for this study
      was LR control. RESULTS: The prognostic score was defined as the number of
      adverse prognostic factors present at diagnosis. Four factors had similarly
      independent prognostic effects (hazard ratio, 2.0-2.6): age >40 years, histologic
      WHO type I-II, serum LDH level > or =410 U/L, and involvement of two or more
      sites of the following anatomic structures, i.e., sphenoid floor, clivus marrow,
      clivus cortex, prevertebral muscles, and petrous bone. The score predicted the 5
      year probability of LR control as follows: 0 (15% of the patients), 100%; 1 (42%
      of the patients), 93%; 2 (29% of the patients), 83%; 3 or higher (13% of the
      patients), 71%. CONCLUSION: This scoring system is useful in the decision-making
      for individual patients and the design of clinical trials to improve LR control
      for advanced-stage NPC.

PMID- 16979833
TI  - Results of the 2004 Association of Residents in Radiation Oncology (ARRO) survey.
AB  - PURPOSE: The aim of this study was to document adequacy of training, career plans
      after residency, use of the in-service examination, and motivation for choice of
      radiation oncology as a specialty. METHODS AND MATERIALS: In 2004, the
      Association of Residents in Radiation Oncology (ARRO) conducted a nationwide
      survey of all radiation oncology residents in the United States. RESULTS: The
      survey was returned by 297 residents (response rate, 54%). Of the respondents,
      29% were female and 71% male. The most popular career choice was joining an
      established private practice (38%), followed by a permanent academic career
      (29%). Residents for whom a permanent academic career was not their first choice
      were asked whether improvements in certain areas would have led them to be more
      likely to pursue an academic career. The most commonly chosen factors that would
      have had a strong or moderate influence included higher salary (81%), choice of
      geographic location (76%), faculty encouragement (68%), and less time commitment
      (68%). Of respondents in the first 3 years of training, 78% believed that they
      had received adequate training to proceed to the next level of training. Of those
      in their fourth year of training, 75% believed that they had received adequate
      training to enter practice. CONCLUSIONS: Multiple factors affect the educational
      environment of physicians in training. Data describing concerns unique to
      resident physicians in radiation oncology are limited. The current survey was
      designed to explore a variety of issues confronting radiation oncology residents.
      Training programs and the Residency Review Committee should consider these
      results when developing new policies to improve the educational experiences of
      residents in radiation oncology.

PMID- 16979834
TI  - Survey on use of postmastectomy radiotherapy for breast cancer in China.
AB  - PURPOSE: To comprehensively assess the current use of postmastectomy radiotherapy
      (PMRT) throughout China. METHODS AND MATERIALS: A questionnaire on the
      indications and techniques for PMRT for breast cancer was mailed to all 715
      radiotherapy centers in mainland China. RESULTS: Of the 715 questionnaires sent
      out, 210 were answered (29.4%). The median interval between surgery and PMRT was
      6 weeks. "Sandwich" sequencing of chemotherapy and PMRT was the most common
      combination, performed in 75.7% of the responding clinics. Of the respondents,
      11.9% used PMRT for T1-T2N0 breast cancer, 63.8% for T1-T2N0 with tumors located
      in the center or inner quadrant, 87.6% for Stage T1-T2 and one to three positive
      lymph nodes (LN+), and 97.1% for T3 or Stage III tumors and/or four or more LN+.
      The supraclavicular region was the most common radiation target used by the
      respondents (96.2%), followed by the internal mammary chain (85.2%), chest wall
      (79.0%), and axilla (74.8%). Photon-based tangential fields were the most common
      technique used for chest wall irradiation (45.8%). The median total dose to each
      target was 50 Gy, with 2-Gy fractions. CONCLUSION: A consensus has been reached
      in China that PMRT is needed for patients with T3 or Stage III disease and/or
      four or more LN+ and that irradiation to the chest wall and supraclavicular
      region is necessary in such patients. However, most Chinese radiation centers are
      also likely to apply PMRT to patients with one to three LN+ and to irradiate the
      internal mammary chain and the axilla.

PMID- 16979835
TI  - Long-term results of intraoperative presacral electron boost radiotherapy (IOERT)
      in combination with total mesorectal excision (TME) and chemoradiation in
      patients with locally advanced rectal cancer.
AB  - BACKGROUND: We analyzed the long-term results of patients with locally advanced
      rectal cancer using a multimodal approach consisting of total mesorectal excision
      (TME), intraoperative electron-beam radiation therapy (IOERT), and pre- or
      postoperative chemoradiation (CRT). PATIENTS AND METHODS: Between 1991 and 2003,
      210 patients with locally advanced rectal cancer (65 International Union Against
      Cancer [UICC] Stage II, 116 UICC Stage III, and 29 UICC Stage IV cancers) were
      treated with TME, IOERT, and preoperative or postoperative CHT. A total of 122
      patients were treated postoperatively; 88 patients preoperatively. Preoperative
      or postoperative fluoropyrimidine-based CRT was applied in 93% of these patients.
      RESULTS: Median age was 61 years (range, 26-81). Median follow-up was 61 months.
      The 5-year actuarial overall survival (OS), disease-free survival (DFS), local
      control rate (LC), and distant relapse free survival (DRS) of all patients was
      69%, 66%, 93%, and 67%, respectively. Multivariate analysis revealed that UICC
      stage and resection status were the most important independent prognostic factors
      for OS, DFS, and DRS. The resection status was the only significant factor for
      local control. T-stage, tumor localization, type of resection, and type of
      chemotherapy had no significant impact on OS, DFS, DRS, and LC. Acute and late
      complications > or =Grade 3 were seen in 17% and 13% of patients, respectively.
      CONCLUSION: Multimodality treatment with TME and IOERT boost in combination with
      moderate dose pre- or postoperative CRT is feasible and results in excellent long
      term local control rates in patients with intermediate to high-risk locally
      advanced rectal cancer.

PMID- 16979836
TI  - Concurrent weekly cisplatin plus external beam radiotherapy and high-dose rate
      brachytherapy for advanced cervical cancer: a control cohort comparison with
      radiation alone on treatment outcome and complications.
AB  - PURPOSE: To test, though a control-cohort study, the hypothesis that concurrent
      chemoradiotherapy (CCRT) using weekly cisplatin, plus high-dose rate
      intracavitary brachytherapy (HDRICB) is superior to radiation (RT) alone in
      patients with advanced cervical cancer. METHODS AND MATERIALS: A total of 171
      patients with Stage IIB-III cervical cancer were enrolled in this study. Seventy
      patients were treated with CCRT and the results were compared with those of 101
      patients who had been treated with RT using the same protocol at an early period.
      RT consisted of 45 Gy in 25 fractions to the whole pelvis, followed by a 12.6-Gy
      boost to the parametrium. Four courses of HDRICB using 6.0 Gy to Point A were
      performed. Chemotherapy consisted of weekly cisplatin at a dose of 40 mg/m(2) for
      5-6 cycles. RESULTS: The 4-year actuarial survival was 74% for the CCRT group and
      68% for the RT group (p = 0.60). The 4-year pelvic relapse-free survival was 87%
      for the CCRT group and 85% for the RT group (p = 0.37). The 4-year distant
      metastases-free survival was 75% for the CCRT group and 76% for the RT group (p =
      0.44). The cumulative incidence of gastrointestinal and genitourinary injuries of
      grade 3 or above was 14.3% for the CCRT group and 7.9% for the RT group (p =
      0.19). CONCLUSION: This study did not show a survival benefit of CCRT with weekly
      cisplatin and HDRICB for Stage II-III cervical cancer, nor did it demonstrate a
      significant increase of late complications when comparing with RT alone.

PMID- 16979837
TI  - Posttreatment prostatic-specific antigen doubling time as a surrogate endpoint
      for prostate cancer-specific survival: an analysis of Radiation Therapy Oncology
      Group Protocol 92-02.
AB  - PURPOSE: We evaluated whether posttreatment prostatic-specific antigen doubling
      time (PSADT) was predictive of prostate cancer mortality by testing the Prentice
      requirements for a surrogate endpoint. METHODS AND MATERIALS: We analyzed
      posttreatment PSA measurements in a cohort of 1,514 men with localized prostate
      cancer (T2c-4 and PSA level <150 ng/mL), treated and monitored prospectively on
      Radiation Therapy Oncology Group Protocol 92-02. From June 1992 to April 1995,
      men were randomized to neoadjuvant androgen deprivation and 65-70 Gy of radiation
      therapy (n = 761), or in combination with 24 months of adjuvant androgen
      deprivation (n = 753). Using an adjusted Cox proportional hazards model, we
      tested if PSADT was prognostic and independent of randomized treatment in this
      cohort. The endpoints were time to PSADT (assuming first-order kinetics for a
      minimum of 3 rising PSA measurements) and cancer-specific survival (CSS).
      RESULTS: After a median follow-up time of 5.9 years, randomized treatment was a
      significant predictor for CSS (p(Cox) = 0.002), PSADT <6 months (p(Cox) < 0.001),
      PSADT <9 months (p(Cox) < 0.001), and PSADT <12 months (p(Cox) < 0.001) but not
      for PSADT <3 (p(Cox) = 0.4). The significant posttreatment PSADTs were also
      significant predictors of CSS (p(Cox)< 0.001). After adjusting for T stage,
      Gleason score and PSA, all of Prentice's requirements were not met, indicating
      that the effect of PSADT on CSS was not independent of the randomized treatment.
      CONCLUSIONS: Prostatic specific antigen doubling time is significantly associated
      with CSS, but did not meet all of Prentice's requirements for a surrogate
      endpoint of CSS. Thus, the risk of dying of prostate cancer is not fully
      explained by PSADT.

PMID- 16979838
TI  - Single-nucleotide polymorphisms in base excision repair, nucleotide excision
      repair, and double strand break genes as markers for response to radiotherapy in
      patients with Stage I to II head-and-neck cancer.
AB  - PURPOSE: Polymorphisms in DNA repair genes can influence response to
      radiotherapy. We analyzed single-nucleotide polymorphisms (SNP) in nine DNA
      repair genes in 108 patients with head-and-neck cancer (HNSCC) who had received
      radiotherapy only. METHODS AND MATERIALS: From May 1993 to December 2004,
      patients with Stage I and II histopathologically confirmed HNSCC underwent
      radiotherapy. DNA was obtained from paraffin-embedded tissue, and SNP analysis
      was performed using a real-time polymerase chain reaction allelic discrimination
      TaqMan assay with minor modifications. RESULTS: Patients were 101 men (93.5%) and
      7 (6.5%) women, with a median age of 64 years (range, 40 to 89 years). Of the
      patients, 76 (70.4%) patients were Stage I and 32 (29.6%) were Stage II. The
      XPF/ERCC1 SNP at codon 259 and XPG/ERCC5 at codon 46 emerged as significant
      predictors of progression (p = 0.00005 and 0.049, respectively) and survival (p =
      0.0089 and 0.0066, respectively). Similarly, when variant alleles of XPF/ERCC1,
      XPG/ERCC5 and XPA were examined in combination, a greater number of variant
      alleles was associated with shorter time to progression (p = 0.0003) and survival
      (p = 0.0002). CONCLUSIONS: Genetic polymorphisms in XPF/ERCC1, XPG/ERCC5, and XPA
      may significantly influence response to radiotherapy; large studies are warranted
      to confirm their role in HNSCC.

PMID- 16979839
TI  - Phase I trial of cetuximab in combination with capecitabine, weekly irinotecan,
      and radiotherapy as neoadjuvant therapy for rectal cancer.
AB  - PURPOSE: To establish the feasibility and efficacy of chemotherapy with
      capecitabine, weekly irinotecan, cetuximab, and pelvic radiotherapy for patients
      with locally advanced rectal cancer. METHODS AND MATERIALS: Twenty patients with
      rectal cancer (clinical Stage uT3-T4 or N+) received a standard dosing regimen of
      cetuximab (400 mg/m(2) on Day 1 and 250 mg/m(2) on Days 8, 15, 22, and 29) and
      escalating doses of irinotecan and capecitabine according to phase I methods:
      dose level I, irinotecan 40 mg/m(2) on Days 1, 8, 15, 22, and 29 and capecitabine
      800 mg/m(2) on Days 1-38; dose level II, irinotecan 40 mg/m(2) and capecitabine
      1000 mg/m(2); and dose level III, irinotecan 50 mg/m(2) and capecitabine 1000
      mg/m(2). Radiotherapy was given to a dose of 50.4 Gy (45 Gy plus 5.4 Gy).
      Resection was scheduled 4-5 weeks after termination of chemoradiotherapy.
      RESULTS: On dose level I, no dose-limiting toxicities occurred; however, Grade 3
      diarrhea affected 1 of 6 patients on dose level II. Of 5 patients treated at dose
      level III, 2 exhibited dose-limiting toxicity (diarrhea in 2 and nausea/vomiting
      in 1). Therefore, dose level II was determined as the recommended dose for future
      studies. A total of 10 patients were treated on dose level II and received a mean
      relative dose intensity of 100% of cetuximab, 94% of irinotecan, and 95% of
      capecitabine. All patients underwent surgery. Five patients had a pathologically
      complete remission and six had microfoci of residual tumor only. CONCLUSION:
      Preoperative chemoradiotherapy with cetuximab, capecitabine, and weekly
      irinotecan is feasible and well tolerated. The preliminary efficacy is very
      promising. Larger phase II trials are ongoing.

PMID- 16979840
TI  - Risk factors of late rectal bleeding after carbon ion therapy for prostate
      cancer.
AB  - PURPOSE: The aim of this study was to determine the risk factors for late
      gastrointestinal (GI) morbidity after hypofractionated carbon ion radiotherapy (C
      ion RT) for prostate cancer. METHODS AND MATERIALS: Between April 2000 and
      November 2003, a Phase II clinical trial of C-ion RT with a total dose of 66 GyE
      in 20 fractions was performed on 175 patients with prostate cancer, and the
      correlations of clinical and dosimetric parameters with the incidence of late GI
      toxicity in 172 patients who survived for more than 18 months were investigated.
      RESULTS: Although no Grade 3-4 late morbidities of the rectum were observed,
      Grade 1 and 2 morbidities developed in 23 (13%) and 4 (2%) patients,
      respectively. Dose-volume histogram analysis revealed that the percentage of
      rectal volume receiving 50% of the prescribed dose (V50) was significantly higher
      in patients with rectal toxicity than without toxicity (13.2 +/- 5.6% with
      toxicity; 11.4 +/- 4.0% without toxicity, p = 0.046). Multivariate analysis
      demonstrated that the use of anticoagulation therapy (p = 0.010) and rectal V50
      (p = 0.012) were significant risk factors for the occurrence of Grade 1-2 late GI
      toxicity. CONCLUSIONS: Although C-ion RT with hypofractionation yielded favorable
      results regarding late GI complication, dosimetric parameter was a very important
      factor in the occurrence of rectal bleeding after C-ion RT as well as photon beam
      RT. Our results provide useful information for physicians applying charged
      particle RT in the treatment of prostate cancer.

PMID- 16979841
TI  - Efficacy of an integrated continuing medical education (CME) and quality
      improvement (QI) program on radiation oncologist (RO) clinical practice.
AB  - PURPOSE: There has been little radiation oncologist (RO)-specific research in
      continuing medical education (CME) or quality improvement (QI) program efficacy.
      Our aim was to evaluate a CME/QI program for changes in RO behavior, performance,
      and adherence to department protocols/studies over the first 12 months of the
      program. METHODS AND MATERIALS: The CME/QI program combined chart audit with
      feedback (C-AWF), simulation review AWF (SR-AWF), reminder checklists, and
      targeted CME tutorials. Between April 2003 and March 2004, management of 75
      patients was evaluated by chart audit with feedback (C-AWF) and 178 patients via
      simulation review audit (SR-AWF) using a validated instrument. Scores were
      presented, and case management was discussed with individualized educational
      feedback. RO behavior and performance was compared over the first year of the
      program. RESULTS: Comparing the first and second 6 months, there was a
      significant improvement in mean behavior (12.7-13.6 of 14, p = 0.0005) and RO
      performance (7.6-7.9 of 8, p = 0.018) scores. Protocol/study adherence
      significantly improved from 90.3% to 96.6% (p = 0.005). A total of 50 actions
      were generated, including the identification of learning needs to direct CME
      tutorials, the systematic change of suboptimal RO practice, and the alteration of
      deficient management of 3% of patients audited during the program. CONCLUSION: An
      integrated CME/QI program combining C-AWF, SR-AWF, QI reminders, and targeted CME
      tutorials effectively improved targeted RO behavior and performance over a 12
      month period. There was a corresponding increase in departmental protocol and
      study adherence.

PMID- 16979842
TI  - Comparison of the prognostic impact of serum anti-EBV antibody and plasma EBV DNA
      assays in nasopharyngeal carcinoma.
AB  - PURPOSE: Nasopharyngeal carcinoma (NPC) has been proven as an Epstein-Barr virus
      (EBV)-associated cancer. Serum anti-EBV antibodies and plasma EBV DNA have been
      investigated as surrogate markers for NPC. A comparison of the prognostic impacts
      of both assays has never been reported. METHODS AND MATERIALS: Paired serum and
      plasma samples from 114 previously untreated NPC patients were collected and
      subjected to an immunofluorescence assay for immunoglobulin (Ig)A and IgG
      antibodies against the viral capsid antigen (VCA) and a real-time quantitative
      polymerase chain reaction assay for EBV DNA measurement. The effects of both
      assays on patient prognosis were thoroughly investigated. RESULTS: Relapsed
      patients had significantly higher pretreatment EBV DNA concentration than
      patients without relapse (p = 0.0006). No associations of VCA-IgA (p = 0.9669) or
      VCA-IgG (p = 0.6125) were observed between patients with and without relapse. The
      4-year overall survival (60.3% vs. 93.1%, p < 0.0001) and relapse-free survival
      rates (54.4% vs. 77.9%, p = 0.0009) were significantly lower in patients with
      higher pretreatment EBV DNA load than in those with lower EBV DNA load. Patients
      with persistently detectable EBV DNA after treatment had significantly worse 4
      year overall (30.8% vs. 84.6%, p < 0.0001) and relapse-free survival rates (15.4%
      vs. 74.0%, p < 0.0001) than those with undetectable EBV DNA. The VCA-IgA and VCA
      IgG titer could not predict survivals (all p > 0.1). Cox multivariate analyses
      also showed the same results. CONCLUSION: Plasma EBV DNA is superior to serum EBV
      VCA antibodies in prognostic predictions for NPC.

PMID- 16979843
TI  - Radiochemotherapy combined with regional pelvic hyperthermia induces high
      response and resectability rates in patients with nonresectable cervical cancer >
      or =FIGO IIB "bulky".
AB  - PURPOSE: To evaluate preoperative radiochemotherapy combined with regional pelvic
      hyperthermia in patients with nonresectable cervical cancer >/= International
      Federation of Gynecology and Obstetrics (FIGO) IIB "bulky" in a Phase II study.
      METHODS AND MATERIALS: Thirty-two patients with nonresectable FIGO IIB-IVA
      cervical cancer confined to the pelvis were treated with radiochemotherapy (5 x
      1.8 Gy/wk, 45-50.4 Gy; cisplatin, 40 mg/m2/wk) and weekly regional pelvic
      hyperthermia (SIGMA-60 applicator, system BSD-2000; BSD Medical Corp., Salt Lake
      City, UT). Responders underwent hysterectomy if possible, whereas patients still
      unresectable received definitive hyperthermic radiochemotherapy. Feasibility,
      toxicity, as well as response and resectability, local progression free- and
      overall survival rates, were evaluated. RESULTS: Thirty of 32 patients completed
      treatment. Grade III/IV toxicities (National Cancer Institute-Common Toxicity
      Criteria) were diarrhea (n = 5), weight loss >10 kg (n = 4), and nausea (n = 2).
      Twenty-four of 32 patients (75%) achieved a partial remission after 45-50 Gy, and
      20 patients underwent hysterectomy (18 patients, R0; 8 patients pCR). Three-year
      overall survival was 60%, with moderate (13%) rates of severe late toxicity. R0
      resected patients had a favorable chronic toxicity profile and an excellent
      prognosis (3-year survival rate: 93%). Response depended on thermal parameters
      (vaginal reference point), whereas response, R0-resection, and FIGO stage are
      significant prognostic factors for survival. CONCLUSION: Preoperative
      hyperthermic radiochemotherapy (45-50 Gy) induces high response rates and enables
      curative surgery in a high proportion of patients with nonresectable cervical
      cancer. Therefore, the use of hyperthermia in conjunction with standard chemo
      /radiotherapy +/- surgery may allow for more effective tumor treatment while
      decreasing the risk of complications in patients with locally advanced cervical
      cancer.

PMID- 16979844
TI  - Low-dose radiotherapy for Stage I seminoma--long-term results.
AB  - PURPOSE: The aim of this study was to review retrospectively the results of low
      dose radiotherapy for Stage I seminoma using four different fractionation
      schedules and target volume definitions. METHODS AND MATERIALS: A total of 191
      patients underwent irradiation for histologically proven Stage I seminoma after
      undergoing an inguinal orchiectomy. Fractionation schedules were used one after
      another as follows: Total dose 30 Gy (dose/fraction 1.5 Gy, 16 patients), total
      dose 25.5 Gy (dose/fraction 1.5 Gy, 62 patients), total dose 20 Gy (dose/fraction
      2 Gy, 69 patients), total dose 26 Gy (dose/fraction 2 Gy, 29 patients). The
      remaining 12 patients were excluded from this study. In the same period the
      target volume was gradually reduced. In 1983 the paraaortic, pelvic and inguinal
      regions were irradiated; later the target volume was reduced to the paraaortic
      region exclusively. RESULTS: Overall survival and event-free survival were
      identical in all groups ranging from 95% to 100% /5 years. Three patients
      experienced a lymph node metastasis during follow-up, 3 patients a distant
      metastasis to the lung and the bones. Mild acute side effects were noted in 8% to
      15% of the patients, and very mild long-term side effects in 1% to 5% of
      patients. Multivariate analysis showed no prognostic significance of total dose,
      dose per fraction, or target volume. In univariate analysis, a higher frequency
      of acute side effects to the skin and the bowel was related to a higher total
      dose, and an elevated frequency of nausea was related to a higher daily dose per
      fraction. CONCLUSION: Using lower doses and limiting the target volume to the
      paraaortic region exclusively did not result in a worse prognosis in our patient
      series.

PMID- 16979845
TI  - Cyclooxygenase-2 impairs treatment effects of radiotherapy for cervical cancer by
      inhibition of radiation-induced apoptosis.
AB  - PURPOSE: Cyclooxygenase-2 (COX-2) plays a pivotal role in regulation of radiation
      induced apoptosis. The aim of this study was to analyze the relationship between
      COX-2 expression and postradiotherapy outcomes of patients with cervical cancer.
      METHODS AND MATERIALS: Biopsy specimens from 47 consecutive patients who had
      undergone definitive radiotherapy alone or radiotherapy combined with
      chemotherapy between October 2002 and November 2004 were investigated. RESULTS:
      The COX-2 expression rate of the pretreatment samples was 46.1% +/- 21.0%, and
      the apoptotic index (AI) 1 week after start of radiotherapy was 2.1% +/- 0.9%.
      There was a significant negative correlation between the pretreatment COX-2
      expression and the AI during radiotherapy (r = -0.52, p = 0.0002). Complete
      response rates were 59% for COX-2-positive patients compared with 80% for COX-2
      negative patients (p = 0.12). The 2-year local control rate for COX-2-positive
      patients was 71.3%, whereas the corresponding rate for COX-2-negative patients
      was 96.0% (p = 0.06). CONCLUSIONS: To the best of our knowledge, this is the
      first report to prove clinically that COX-2 can make cervical squamous cell
      carcinomas more refractory to radiotherapy by inhibition of radiation-induced
      apoptosis. Furthermore, expression of COX-2 may be a good indicator to predict
      local tumor control after radiotherapy. Although long-term results are ultimately
      needed, the combination therapy of radiotherapy with use of a COX-2 inhibitor
      could yield improved outcomes for patients with COX-2 expressing cervical cancer.

PMID- 16979846
TI  - The role of temporal generalization in a temporal discrimination task.
AB  - Two experiments trained rats to discriminate two or three stimulus durations
      using a temporal discrimination task. A standard peak shift effect was observed
      when training was administered with short versus long signals in Experiment 1.
      Both discrimination accuracy scores and the generalization gradients revealed
      that shorter intervals were discriminated more accurately, which may be due to
      the scalar property of timing. In Experiment 2, three signals (short, medium, and
      long) were associated with three different responses, or two of the intervals
      were associated with one response (short and long or short and medium) and the
      other interval with a different response. Here, the short/medium versus long
      discrimination was learned most readily of the three tasks. The results of both
      experiments indicated a strong contribution of learning of individual durations
      combined with scalar generalization gradients, but Experiment 2 indicated that
      categorical encoding of durations may have also been operating.

PMID- 16979847
TI  - Disulfiram effects on responses to intravenous cocaine administration.
AB  - Disulfiram has been studied as a treatment for cocaine dependence. We report
      results of a randomized, double-blind, placebo-controlled, within-subject study
      to examine the interaction of disulfiram with intravenous cocaine. METHODS: Non
      treatment-seeking, cocaine-dependent, volunteers participated in serial
      experiments in which they received disulfiram placebo, 62.5 or 250 mg/day on days
      1-6. On days 4-6, participants received a morning disulfiram dose 2 h prior to a
      scheduled session in which they were administered intravenous cocaine placebo,
      0.25 mg/kg (n=9) or 0.5 mg/kg (n=3) over 1 min. Blood, cardiovascular and
      subjective measures were collected. Seven days of washout occurred between
      disulfiram conditions. RESULTS: Following active disulfiram treatments and
      cocaine 0.25 mg/kg administration, plasma cocaine AUC (0-480 min) was increased
      (p=0.003 and 0.001) and cocaine clearance decreased (p<0.001). Disulfiram
      treatments also decreased cocaine clearance for the 0.5 mg/kg cocaine dose
      (p=0.002 and<0.001). Neither disulfiram dose with cocaine altered cardiovascular
      responses relative to cocaine alone. Following cocaine 0.25 mg/kg, 'any high'
      (p=0.021 and 0.019), 'cocaine high' (p=0.017 and 0.018) and 'rush' (p=0.013 and
      0.047) significantly decreased with either disulfiram dose. CONCLUSIONS:
      Disulfiram decreased cocaine clearance without toxicity. Cocaine 'high' and
      'rush' were diminished. Disulfiram may be a promising pharmacotherapy in selected
      cocaine dependent individuals.

PMID- 16979849
TI  - Differential evolutionary rates of duplicated genes in protein interaction
      network.
AB  - In the network of protein-protein interactions (PPIs), a loss and gain of the
      partnering proteins can cause drastic changes of network formation during
      evolution. With the aim of examining the evolutionary effects of the loss and
      gain of the partnering proteins on PPIs, we examined a relationship between
      evolutionary rates and losses and/or gains of PPIs for duplicated gene pairs
      encoding proteins involved in the PPI network. For duplicated pairs, which
      provided us with a unique opportunity of making fair comparisons of the genes
      with the same initial condition, we found that the evolutionary rate of the
      protein with more PPI partners is much slower than that of the other with fewer
      PPI partners. Moreover, when the ratio of evolutionary rates (faster rate/slower
      rate) was computed for each of the duplicated pairs, the ratio for the duplicated
      pair sharing any PPI partners was significantly lower than that for the pair
      sharing no PPI partners. These results indicate that the duplicated gene pairs
      differentiate through the losses and/or gains of the PPI partners, resulting in a
      change in their evolutionary rates. In particular, we point out that the PPI
      losses for the duplicated gene products that are involved in the functional
      classes of 'transcription' and 'protein fate' have an impact on their
      evolutionary rates more than the PPI losses for others.

PMID- 16979848
TI  - First injection of ketamine among young injection drug users (IDUs) in three U.S.
      cities.
AB  - Ketamine, a dissociative anesthetic, has emerged as an increasingly common drug
      among subgroups of young injection drug users (IDUs) in cities across the United
      States. In-depth qualitative interviews were conducted with 213 young IDUs aged
      16-28 years recruited in New York, New Orleans, and Los Angeles between 2004 and
      2006. While some initiated injection drug use with ketamine, the drug was more
      frequently injected by IDUs with extensive polydrug using histories. IDUs
      initiating with ketamine commonly self-injected via an intramuscular mode of
      administration. The injection group provided crucial knowledge and material
      resources that enabled the injection event to occur, including ketamine,
      syringes, and injection skills. Injection paraphernalia was commonly shared
      during the first injection of ketamine, particularly vials of pharmaceutically
      packaged liquid ketamine. Injection events infrequently occurred in a rave or
      club and more typically in a private home, which challenges ketamine's
      designation as a 'club' drug. The first injection of ketamine was a noteworthy
      event since it introduced a novel drug or new mode of administration to be
      further explored by some, or exposed others to a drug to be avoided in the
      future. Risk reduction messages directed towards young IDUs should be expanded to
      include ketamine.

PMID- 16979850
TI  - Salmonella in free living terrestrial and aquatic turtles.
AB  - Detection of Salmonella in pet turtles has been the focus of extensive research,
      but its incidence in free living turtles is not well known. The aim of this study
      was to evaluate the incidence of Salmonella in terrestrial and aquatic species of
      chelonians inhabiting a National Park in southwestern Spain. Individuals of the
      terrestrial tortoise Testudo graeca (n = 16) and the aquatic turtles Emys
      orbicularis (n = 26) and Mauremys leprosa (n = 50) were investigated. Maximum
      incidence of Salmonella was recorded in the terrestrial species (100%). In
      contrast, the incidence of infected animals was low in the aquatic species, 12%
      in M. leprosa and 15.4% in E. orbicularis. Five serotypes of Salmonella belonging
      to subspecies enterica (I) and salamae (II) were identified. All serotypes were
      found in the terrestrial species, and three in the aquatic ones, suggesting that
      wild terrestrial chelonians are important reservoirs of Salmonella in our study
      area. Cloacal transmission during mating is the most probable mode of
      transmission among individuals.

PMID- 16979851
TI  - Salmonella Montevideo outbreak in military kennel dogs caused by contaminated
      commercial feed, which was only recognized through monitoring.
AB  - A large outbreak of canine salmonellosis in military watch dogs due to Salmonella
      Montevideo and/or Salmonella Give was only recognized through a monitoring
      program, implemented by the military forces. In 51 out of 80 exposed dogs (63.8%)
      from four kennels Salmonella was isolated from fecal samples. The prevalence per
      sampling day ranged from 5.6 to 77.8%. Clinical disease with mild diarrhea but
      without fever appeared only in nine dogs (11.3% of study population, 16.9% of
      cases) from one kennel (***P < 0.001). Risk analysis identified "dog food A"
      (odds ratio 3.33 [1.12 < OR < 10.06] *P < 0.05) and "dog food C" (odds ratio 3.40
      [1.07 < OR < 11.22] *P < 0.05), two commercial dehydrated dog feeds, as suspected
      infectious sources. Feeding "dog food C" alone or together with "dog food A" was
      significantly associated with clinical disease (***P < 0.001). S. Montevideo and
      S. Give with similar plasmid profiles and PFGE-restriction patterns were isolated
      from the suspected dog feeds and fecal samples. This outbreak demonstrates not
      only that Salmonella infections in dogs occur without clinical symptoms but also
      that large outbreaks occur after feeding dehydrated dog feeds. Especially in
      households with known risk group patients this finding demonstrates a particular
      risk for their owners, as they often live in close contact with their animals.

PMID- 16979852
TI  - Cholesterol oxidase (ChoE) is not important in the virulence of Rhodococcus equi.
AB  - To analyze further the role in virulence of the prominent cholesterol oxidase
      (ChoE) of Rhodococcus equi, an allelic exchange choE mutant from strain 103+ was
      constructed and assessed for virulence in macrophages, in mice, and in foals.
      There was no difference between the mutant and parent strain in cytotoxic
      activity for macrophages or in intra-macrophage multiplication. No evidence of
      attenuation was obtained in macrophages and in mice, but there was slight
      attenuation apparent in four intra-bronchially infected foals compared to
      infection of four foals with the virulent parent strain, based on a delayed rise
      in temperature of the choE-mutant infected foals. However, bacterial colony
      counts in the lung 2 weeks after infection were not significantly different,
      although there was a slight but non-significant (P=0.12) difference in lung:body
      weight ratio of the choE mutant versus virulent parent infected foals (mean
      2.67+/-0.25% compared to 4.58+/-0.96%). We conclude that the cholesterol oxidase
      is not important for the virulence of R. equi.

PMID- 16979853
TI  - Power spectral analysis of two-channel EEG in hypoxic-ischaemic encephalopathy.
AB  - AIMS: Power spectral analysis combined with a two-channel EEG system may be
      useful in management of newborn term infants at risk of hypoxic-ischaemic
      encephalopathy (HIE). This pilot study aimed to determine differences in the EEG
      power spectrum between normal term infants, infants who were at risk of but had
      not developed HIE, and infants who had developed HIE. DESIGN: Observational.
      METHODS: EEG recordings from normal term newborn infants and term infants at risk
      of HIE were analyzed using fast Fourier transforms. EEG total power (TP), TP
      variance, TP coefficient of variation (TP CV) and spectral edge frequency (SEF)
      were compared between three groups: control infants (n=15); at-risk infants who
      had not developed clinically diagnosed HIE (n=4); and at-risk infants who had
      developed HIE (n=7). RESULTS: Total power was similar in all groups. Variation of
      TP (variance and CV) was higher (p<0.05) in control infants than in infants at
      risk of HIE, regardless of whether they had developed HIE. SEF values were
      similar across all three groups. CONCLUSION: Reduced variation of EEG power is a
      feature of infants at risk of HIE.

PMID- 16979854
TI  - A randomized study of the efficacy of sensory-motor-oral stimulation and non
      nutritive sucking in very low birthweight infant.
AB  - To assess if sensory-motor-oral stimulation and non-nutritive sucking gavage
      feeding enhances the oral feeding performance of preterm infants born between 26
      and 32 weeks of gestational age. STUDY DESIGN: Very low birthweight infants
      (n=98) were randomized into a experimental and control group. Preterm infants in
      the experimental group received sensory-motor-oral stimulation and non-nutritive
      sucking and infants in the control group received a sham stimulation program.
      Both were administered from when they reached enteral diet (100 kcal/kg/day)
      until the beginning of oral diet. Primary outcome was length of hospital stay.
      RESULTS: Independent oral feeding was attained significantly earlier in the
      experimental group than the control group, 38+/-16 days of life (mean+/-S.D.)
      versus 47+/-17 days of life, respectively (P<0.001) There was significant
      difference in length of hospital stay between the two groups (41.9+/-17 (mean+/
      S.D.) versus 52.3+/-19 days (P<0.01)). CONCLUSION: Sensory-motor-oral
      stimulation, together with early non-nutritive sucking (as soon as the newborn
      reaches full diet and is clinically stable) in very low birthweight preterm
      infants, as long as they are clinically stable, in this study, earlier initiation
      of oral feeding and earlier hospital discharge.

PMID- 16979855
TI  - A new method of blood sampling reduces pain for newborn infants: a prospective,
      randomized controlled clinical trial.
AB  - BACKGROUND: Using a new simple blood glucose measurement device (Free Style),
      blood can thus be sampled from the forearm, which is less sensitive to pain than
      from the heel. Measuring the blood glucose levels in newborn infants using Free
      Style is therefore a potentially less painful testing modality than traditional
      blood sampling methods. OBJECTIVE: To compare the pain intensity at the time of
      blood sampling from the forearm using the Free Style with the conventional method
      from the heel. DESIGN: A prospective, randomized controlled clinical trial.
      PATIENTS AND METHODS: Sixty healthy neonates were randomized by the sealed
      envelope method into two groups-Group F, in which blood was sampled from the
      forearm using the Free Style, and Group H, in which blood was conventionally
      sampled from the heel using a lancet. The pain intensity was assessed based on
      their crying, the Neonatal Facial Coding System (NFCS) and the Neonatal Infant
      Pain Scale (NIPS). RESULTS: After skin puncture, 12 (40%) of the infants cried in
      Group F and 27 (90%) in Group H. The duration of crying was also significantly
      shorter in Group F than in Group H. Both of pain scores between the two groups
      differed significantly, these findings indicated less pain for Group F.
      CONCLUSION: The new blood sampling method from the forearm was found to be less
      painful than the conventional method, thus making it possible to clinically use
      this product as an innovative method for blood sampling in neonatal medicine.

PMID- 16979856
TI  - Phonology, rapid naming and academic achievement in very preterm children at
      eight years of age.
AB  - AIM: To examine the impact and additive effect of phonology and rapid naming
      deficits on reading, spelling and mathematics achievement in a group of very
      preterm children at 8 years of age. METHODS: All surviving children with a
      gestational age less than 30 weeks, admitted to the neonatal intensive care unit
      at Royal Prince Alfred Hospital, in 1994 and 1995, were prospectively enrolled in
      developmental follow-up. Children with a neurosensory disability or a low
      intelligence score (FSIQ<or=85 points) were excluded. At 8 years of age
      standardised psychometric measures of cognition, linguistic ability and academic
      achievement were administered to a sample of 63 children. RESULTS: Twenty-four
      (38.1%) children showed low achievement in reading, spelling or mathematics. Of
      these, 18 (75%) children showed low achievement in reading. Reading achievement
      was significantly correlated to phonological awareness, rapid naming and
      expressive vocabulary. Children with phonological awareness and rapid naming
      deficits showed significantly more delay in reading than children without such
      deficits. Children who had rapid naming deficits were more likely to show
      multiple skill delays. Rapid naming showed significant, though modest
      correlations with immaturity and illness variables. Maternal education was
      significantly associated with achievement. CONCLUSIONS: Phonological awareness
      does predict reading performance in very preterm children. Rapid naming appears
      to be related to complex multiple academic delays, and may reflect a neurological
      timing or efficiency factor with effects independent of intelligence and
      significantly influenced by immaturity and illness.

PMID- 16979858
TI  - A herd health approach to dairy cow nutrition and production diseases of the
      transition cow.
AB  - This paper presents a practical, on-farm approach for the monitoring and
      prevention of production disease in dairy cattle. This integrated approach,
      should be used in an interdisciplinary way by farmers, veterinarians, nutrition
      advisors and other relevant professionals for the improvement of animal health
      and welfare and producer profitability. The key areas that form the basis for
      this approach are body condition score management, negative energy balance,
      hypocalcaemia, rumen health and trace element status. Monitoring criteria are
      described for each of these key areas, which when considered collectively, will
      facilitate the assessment of dairy cow health with regard to clinical and
      subclinical disease. The criteria, which are informed by published scientific
      literature, are based on farm management and environmental factors, clinical
      data, milk production records, dietary analysis, and assessment of blood and
      liver concentrations of various metabolites or trace elements. The aim is to
      review the efficacy of production disease control measures currently in place,
      and if necessary to modify them or formulate new ones.

PMID- 16979857
TI  - Relationships between adrenocorticotropic hormone and cortisol are altered during
      clustered nursing care in preterm infants born at extremely low gestational age.
AB  - BACKGROUND: Little is known about the effects of clustered nursing care on
      hypothalamic pituitary axis (HPA) responses in preterm infants in the neonatal
      intensive care unit. AIMS: To examine facial responses, adrenocorticotropic
      hormone (ACTH) and cortisol levels, and the relationship between ACTH and
      cortisol in preterm infants in two gestational age groups (extremely low
      gestational age [ELGA: < or =28 weeks]; very low gestational age [VLGA: 29-31
      weeks]) under basal conditions and in response to routine nursing procedures.
      STUDY DESIGN: Within subjects' cross-over design in random order. SUBJECTS:
      Ninety preterm infants with no postnatal steroid exposure were studied at 32+/-1
      weeks postconceptional age. OUTCOME MEASURES: Facial actions, ACTH and cortisol
      levels were measured after a 30 minute rest period and in response to routine
      clustered nursing care (CC). Changes in facial actions were analyzed using
      repeated measures ANOVA. MANOVA or Mann-Whitney U tests were used to determine
      differences in ACTH and cortisol between gestational age groups. Spearman rank
      correlations were used to examine relationships between perinatal variables and
      facial, ACTH and cortisol levels. RESULTS: All infants had significantly
      increased facial responses to CC (p=0.001). Infants having experienced higher
      numbers of skin breaking procedures 24 h before basal assessment had higher basal
      cortisol levels (r=0.30, p=0.01). In response to CC, ELGA infants showed no
      correlation between ACTH and cortisol levels; VLGA infants showed a strong,
      positive correlation (r=0.62, p=0.02). CONCLUSION: The pattern of relationship
      between ACTH and cortisol differs depending on gestational age at birth in
      response to clustered nursing care. Prior pain alters responsiveness and HPA
      dysregulation is apparent in ELGA infants.

PMID- 16979859
TI  - New GnRH analogs in canine reproduction.
AB  - Gonadotropin-releasing hormone (GnRH) analogs, which include agonists and
      antagonists, have been produced by amino acid substitutions of the native GnRH
      molecule to create greater potency and longer duration of effectiveness. The aim
      of this article was to review the pharmacological effects and the existing
      clinical literature of new GnRH analogs, namely agonists released from long-term
      formulations and third generation antagonists, in domestic dogs. Long-term
      administration of agonists functions through desensitization and down-regulation
      of GnRH pituitary receptors inhibiting gonadotropin production and release after
      an initial stimulation. Conversely, GnRH antagonists bind to gonadotrope GnRH
      receptors and compete successfully with endogenous GnRH for occupancy, thereby
      inhibiting the pituitary-gonadal axis immediately. There is a promising place for
      both agonists and antagonists in future canine reproduction. They can be used in
      the control of estrous cycle, hormone-dependent diseases as well as in
      contraception. Some information on the effectiveness and safety of these new
      analogs in canine reproduction is already available, yet further work is needed
      before they could be widely recommended. The increase in gonadotropins and
      gonadal steroids following administration of agonists might have adverse effects
      when used on hormone-dependent diseases. This initial "flare" should also be
      carefully managed in anestrous and prepubertal bitches. At present, the main
      application of antagonists seems limited to situations where an acute endocrine,
      inhibitory effect is required, e.g. proestrus or pregnancy termination. Future
      commercial availability of long-acting, single-dose antagonists could go far
      towards controlling pet population.

PMID- 16979860
TI  - Determination of n-octanol/water partition and membrane binding of cationic
      porphyrins.
AB  - Porphyrin and their derivatives are being systematically studied as
      photosensitizers for photodynamic therapy. The ability to predict their membrane
      partition properties is of key importance to unveil their in vivo activity and
      applications. Several n-octanol/water partition coefficients (logP(OW)) of
      porphyrin derivatives have been reported in the literature but large
      discrepancies have been observed. Reproducible and reliable logP(OW) data for a
      series of 20 cationic meso-phenyl(pyridyl)porphyrin derivatives were determined
      by correlating logP(OW) with the partition coefficients measured in a more
      adequate n-butanol/water system. Linear correlations as a function of the number
      of positively charged groups bound to the periphery of the porphyrin rings were
      found within each series. A significant effect of the stereochemistry and nature
      of the positively charged substituents was also observed, but diminished steadily
      converging to a similar value in the mono-substituted derivatives. Binding
      constants to liposomes were shown to be proportional to logP(OW), except for the
      cis-isomers of doubly charged porphyrins. The cis-isomer presented smaller
      logP(OW) and higher membrane affinity. The effect was explained based on the
      amphiphilic nature of the cis-porphyrin.

PMID- 16979861
TI  - The application of DNA micro-arrays (gene arrays) to the study of herbal
      medicines.
AB  - DNA micro-arrays (gene arrays) have become a popular and useful tool with which
      to study the effects of various agents and treatments on gene expression in cells
      and tissues. In theory one can simultaneously evaluate, in a single experiment,
      changes in gene expression (at the level of transcription) of the entire genome
      of the organism under study. Consequently these techniques have been used by many
      investigators interested in cancer research, differentiation and development,
      toxicology, and the effects of pharmaceuticals on cells and animals. In addition,
      recent studies have shown the capacity of the technique for revealing the
      importance of genes not previously implicated in a given response. However,
      relatively few attempts have been made so far to evaluate herbal medicines,
      although the potential to answer a number of relevant questions is there. In this
      review we first discuss the fundamental principles of the gene array technology,
      focusing on the individual steps in the process and their problems and pitfalls,
      and we discuss the analysis and interpretation of the data, the discipline of bio
      informatics, without which meaningful evaluation of gene expression changes would
      be impossible. We next analyze specific studies, which utilized gene array
      technology, aimed at evaluating the effects of certain herbal medicine formulas
      and bioactive ingredients in animal tissues and in cell cultures. We also include
      a brief description of our own evaluation of Echinacea, which we have been
      studying for several years, to indicate possible mechanisms of action of this
      herbal, and also to illustrate how the techniques, especially the bio
      informatics, continue to evolve. We believe, on the basis of experience acquired
      by us and other investigators to date, that the technology of gene array analysis
      can make significant contributions to understanding how herbal medicines work,
      and therefore can validate their applications in medicine.

PMID- 16979862
TI  - Serial diffusion-weighted imaging of neonatal herpes encephalitis: a case report.
AB  - We reported a patient with neonatal herpes simplex encephalitis in whom diffusion
      weighted imaging was performed repeatedly. Diffusion-weighted imaging at 20h
      after the onset of seizures revealed scattered small spotty high intensity
      lesions in both hemispheres and a high intensity area in the left fronto-temporal
      lobe. There was no abnormal finding on conventional magnetic resonance imaging.
      Second diffusion-weighted imaging 72h after the onset revealed expanded scattered
      high intensity lesions in the bilateral hemisphere, a high intensity area in the
      left fronto-temporal lobe, and a new high intensity area in the right temporal
      lobe. There was no report on neonatal herpes simplex encephalitis that showed
      scattered high intensities in diffusion-weighted imaging. Scattered small high
      intensities on diffusion-weighted imaging may suggest endothelial cell infection
      with swelling and small vessel necrosis. Early diffusion-weighted imaging will be
      valuable for early detection and diagnosis of neonatal herpes simplex
      encephalitis.

PMID- 16979863
TI  - Mandibular advancement and morphological changes in the mandibles of female mice
      of different ages.
AB  - Mandibular advancement (MA) by means of functional orthopedic techniques is
      currently used in young patients to stimulate mandibular growth. The aim of this
      study was to evaluate the morphological changes in the mandibles of 2-, 7-, and
      16-month-old female mice after MA. Every 3 days during 1 month, the lower
      incisors were trimmed by 1mm to induce protrusion when the animal was feeding.
      The left mandibles of the 30 experimental and 28 control individuals were
      subsequently dissected and digital images were obtained to analyze nine
      linear/angular measurements. The condylar microstructure was also analyzed by
      scanning electron microscopy (SEM). The linear/angular measurements showed a
      growth response in different mandibular regions in 2- and 16-month-old
      individuals. SEM showed that, in the 7-month-old mice, the condylar cartilage had
      regenerated in the treated individuals but not in the controls. The results
      suggest that MA produces mandibular growth in 2- and 16-month-old female mice.
      Although there was no mandibular growth in 7-month-old mice, regeneration of the
      condylar cartilage was detected, thus demonstrating that different responses to
      the MA stimulus occur in female mice of different ages.

PMID- 16979864
TI  - Development and validation of a LC-MS/MS method with electrospray ionization for
      determination of LASSBio-579 in rat plasma.
AB  - A simple and sensitive LC-MS/MS analytical method was developed and validated for
      the determination of LASSBio-579 in plasma rat, using fluconazole as internal
      standard. Analyses were performed on a Shimadzu HPLC system using a Shimadzu C18
      column and isocratic elution with acetonitrile-water (80:20, v/v), containing
      0.4mM ammonium hydroxide and 0.2 mM acetic acid at a flow rate of 1.0 ml/min
      (split ratio 1:5). A Micromass triple quadrupole mass spectrometer, equipped with
      an electrospray ionization interface, operated in the positive mode. Plasma
      samples were deproteinized with acetonitrile (1:2) and 50 microl of the
      supernatant were injected into the system. The retention times of LASSBio-579 and
      IS were approximately 4.7 and 2.4 min, respectively. Calibration curves in spiked
      plasma were linear over the concentration range of 30-2000 ng/ml with
      determination coefficient >0.98. The lower limit of quantification was 30 ng/ml.
      The accuracy of method was within 15%. Intra- and inter-day relative standard
      deviations were less or equal to 13.5% and 6.4%, respectively. The applicability
      of the LC-MS/MS method for pharmacokinetic studies was tested using plasma
      samples obtained after intraperitoneal administration of LASSBio-579 to male
      Wistar rats. No interference from endogenous substances was observed, showing the
      specificity of the method developed. The reported method can provide the
      necessary sensitivity, linearity, precision, accuracy, and specificity to allow
      the determination of LASSBio-579 in pre-clinical pharmacokinetic studies.

PMID- 16979865
TI  - Simple high performance liquid chromatographic assay for mycophenolic acid in
      renal transplant patients.
AB  - A selective and highly accurate HPLC-UV method is described to determine plasma
      concentrations of mycophenolic acid (MPA), the active metabolite of the prodrugs
      Cellcept and Myfortic. The method is simple and utilizes acidification of plasma
      and protein precipitation step using a mixture of acetonitrile and phosphate
      buffer (pH 3). Following vortex mixing and centrifugation, the supernatant (50
      microL) was injected onto a Zorbax Eclipse XDB C(18) column (150 mm x 4.6 mm
      I.D., 5 microm particle size). A mobile phase composed of acetonitrile and 0.1 M
      phosphate buffer, pH 3 (43:57) delivered at 1.0 mL/min produced peaks for MPA and
      the internal standard (Naproxen) in <7 min. Calibration curves were linear
      (r(2)>0.994) from 1.0-40 microg/mL with intra- and inter-day precision <15% and
      accuracy >95%. The method's improved sensitivity (LOQ=1.0 microg/mL) and minimal
      sample processing allowed rapid monitoring of MPA in human plasma.

PMID- 16979866
TI  - CD105-assessed micro-vessel density is associated with malignancy recurrence in
      laryngeal squamous cell carcinoma.
AB  - AIMS: Angiogenesis is essential for malignancies growth. CD105 is a proliferation
      associated protein abundantly expressed in angiogenic endothelial cells. The aim
      of this study has been to determine the expression of CD105 in laryngeal squamous
      cell carcinoma (SCC) and to investigate the role of CD105-assessed mean vascular
      density (MVD) in predicting patients' prognosis. METHODS: The sections of 43
      consecutive cases of laryngeal SCC were stained with mouse monoclonal antibody
      CD105. All the measures were performed by a computer-based image analysis system.
      The percentage of the fields occupied by CD105-assessed micro-vessels was
      determined. RESULTS: The mean CD105-assessed MVD were 11% and 6% in laryngeal SCC
      with and without malignancy recurrence, respectively. Multivariate logistic
      regression stated that CD105-assessed MVD was significantly related to disease
      recurrence (p=0.030). CONCLUSIONS: Our preliminary results suggest that CD105
      assessed MVD may be a valuable parameter for predicting patients having an
      increased risk of developing laryngeal carcinoma loco-regional recurrence.

PMID- 16979867
TI  - Aluminum toxicity triggers the nuclear translocation of HIF-1alpha and promotes
      anaerobiosis in hepatocytes.
AB  - Although aluminum (Al) is known to be toxic, the exact molecular events that
      enable this trivalent metal to be involved in various diseases have not been
      fully delineated. In this report, we show that Al promotes the translocation of
      the HIF-1alpha (hypoxia inducible factor) to the nucleus and activates the
      anaerobic metabolism of D-glucose. Al-exposed hepatocytes (HepG2 cells) showed a
      marked increase in HIF-1alpha that was associated with nuclear extracts. D
      Glucose consumption in these Al-stressed cells was rapid as more GLUT-1
      transporter was expressed. Furthermore, these Al-treated HepG2 cells were
      characterized with enhanced activities of such metabolic enzymes as hexokinase
      (HK), pyruvate kinase (PK), lactate dehydrogenase (LDH) and glucose 6-phosphate
      dehydrogenase (G6PDH). (13)C- NMR studies pointed to a metabolic profile in Al
      stressed cells that favored enhanced glycolysis. HPLC analyses confirmed
      increased glycolytic ATP production in Al-exposed hepatocytes. These findings
      reveal the ability of Al to create a hypoxic environment that promotes the
      translocation of HIF-1alpha to the nucleus and stimulates the anaerobic
      metabolism of D-glucose.

PMID- 16979868
TI  - Self- and informant reports of executive function on the BRIEF-A in MCI and older
      adults with cognitive complaints.
AB  - Amnestic mild cognitive impairment (MCI) is characterized by impaired episodic
      memory, although subtle executive problems have been noted on neuropsychological
      tests. Recent research also has described a group of healthy, non-depressed older
      adults with significant cognitive complaints (CC) but normal performance on
      neuropsychological testing. These individuals show structural and functional
      brain changes intermediate between those seen in MCI and healthy older adults
      without such complaints (HC). We evaluated executive functions in MCI and CC
      using the Behavior Rating Inventory of Executive Function-Adult version (BRIEF
      A), a newly developed self- and informant report questionnaire in 29 patients
      with amnestic MCI, 28 CCs, and 30 demographically matched HCs. MCI and CC
      participants reported significant difficulties with selective aspects of
      executive functioning relative to HCs despite clinically normal performance on
      neuropsychological tests of this cognitive domain. Scores were generally in the
      pattern of MCI>CC>HC, and findings were most pronounced for working memory.
      Additionally, MCI and CC participants were more likely than their informants to
      report clinically meaningful executive problems, though informants identified a
      similar pattern of difficulty overall. Results failed to reveal strong relations
      between the BRIEF-A and standardized neuropsychological tests of executive
      function. Overall findings indicate that the BRIEF-A is sensitive to subtle
      executive changes in MCI and CC and suggest the need for research to determine if
      executive complaints are predictive of clinical course.

PMID- 16979869
TI  - Ranking analysis of microarray data: a powerful method for identifying
      differentially expressed genes.
AB  - Microarray technology provides a powerful tool for the expression profile of
      thousands of genes simultaneously, which makes it possible to explore the
      molecular and metabolic etiology of the development of a complex disease under
      study. However, classical statistical methods and technologies fail to be
      applicable to microarray data. Therefore, it is necessary and motivating to
      develop powerful methods for large-scale statistical analyses. In this paper, we
      described a novel method, called Ranking Analysis of Microarray Data (RAM). RAM,
      which is a large-scale two-sample t-test method, is based on comparisons between
      a set of ranked T statistics and a set of ranked Z values (a set of ranked
      estimated null scores) yielded by a "randomly splitting" approach instead of a
      "permutation" approach and a two-simulation strategy for estimating the
      proportion of genes identified by chance, i.e., the false discovery rate (FDR).
      The results obtained from the simulated and observed microarray data show that
      RAM is more efficient in identification of genes differentially expressed and
      estimation of FDR under undesirable conditions such as a large fudge factor,
      small sample size, or mixture distribution of noises than Significance Analysis
      of Microarrays.

PMID- 16979870
TI  - Vocal problems among teachers: evaluation of a preventive voice program.
AB  - Vocal education programs for teachers may prevent the emergence of vocal
      disorders; however, only a few studies have tried to evaluate the effectiveness
      of these preventive programs, particularly in the long term. Two hundred and
      sixty-four subjects, mostly kindergarten and primary school female teachers,
      participated in a course on voice care, including a theoretical seminar (120
      minutes) and a short voice group therapy (180 minutes, small groups of 20
      subjects). For 3 months, they had to either attend the vocal ergonomics norms
      and, as psychological reinforcement, they had to make out a daily report of vocal
      abuse, or to follow the given exercises for a more efficient vocal technique,
      reporting on whether the time scheduled was respected or not. The effectiveness
      of the course was assessed in a group of 21 female teachers through a randomized
      controlled study. Evaluation comprehended stroboscopy, perceptual and electro
      acoustical voice analysis, Voice Handicap Index, and a course benefit
      questionnaire. A group of 20 teachers matched for age, working years, hoarseness
      grade, and vocal demand served as a control group. At 3 months evaluation,
      participants demonstrated amelioration in the global dysphonia rates (P=0.0003),
      jitter (P=0.0001), shimmer (P=0.0001), MPT (P=0.0001), and VHI (P=0.0001). Twelve
      months after the course, the positive effects remained, although they were
      slightly reduced. In conclusion, a course inclusive of two lectures, a short
      group voice therapy, home-controlled voice exercises, and hygiene, represents a
      feasible and cost-effective primary prevention of voice disorders in a
      homogeneous and well-motivated population of teachers.

PMID- 16979871
TI  - Brain mechanism of reward prediction under predictable and unpredictable
      environmental dynamics.
AB  - In learning goal-directed behaviors, an agent has to consider not only the reward
      given at each state but also the consequences of dynamic state transitions
      associated with action selection. To understand brain mechanisms for action
      learning under predictable and unpredictable environmental dynamics, we measured
      brain activities by functional magnetic resonance imaging (fMRI) during a Markov
      decision task with predictable and unpredictable state transitions. Whereas the
      striatum and orbitofrontal cortex (OFC) were significantly activated both under
      predictable and unpredictable state transition rules, the dorsolateral prefrontal
      cortex (DLPFC) was more strongly activated under predictable than under
      unpredictable state transition rules. We then modelled subjects' choice
      behaviours using a reinforcement learning model and a Bayesian estimation
      framework and found that the subjects took larger temporal discount factors under
      predictable state transition rules. Model-based analysis of fMRI data revealed
      different engagement of striatum in reward prediction under different state
      transition dynamics. The ventral striatum was involved in reward prediction under
      both unpredictable and predictable state transition rules, although the dorsal
      striatum was dominantly involved in reward prediction under predictable rules.
      These results suggest different learning systems in the cortico-striatum loops
      depending on the dynamics of the environment: the OFC-ventral striatum loop is
      involved in action learning based on the present state, while the DLPFC-dorsal
      striatum loop is involved in action learning based on predictable future states.

PMID- 16979872
TI  - Signalling complexes associated with adenylyl cyclase II are assembled during
      their biosynthesis.
AB  - We have previously demonstrated that adenylyl cyclase II (ACII) interacts with
      beta2-adrenergic receptors and heterotrimeric G proteins as part of a pre
      assembled signalling complex. In this study, we further show that AC interacts
      with these proteins before it is targetted to the cell surface. Using a
      combination of approaches including bioluminescence resonance energy transfer
      (BRET) in concert with subcellular fractionation, we show that ACII and beta2AR
      initially interact in the ER. Further, dominant-negative Rab1 and Sar1 GTPases
      which block anterograde trafficking out of the ER have no effect on either
      ACII/receptor or ACII/Gbetagamma protein interactions. However, DN Rab1 and Sar1
      constructs (but not DN Rabs 2, 6, 8 or 11) prevent the inclusion of Galpha
      subunits in ACII signalling complexes suggesting it assembles into the complex at
      a slightly later stage. Thus, like Kir3.1 inwardly rectifying potassium channels,
      signalosomes containing ACII are formed during their biosynthesis and not in
      response to agonist at the cell surface.

PMID- 16979873
TI  - Upregulated expression of kappa light chain by Epstein-Barr virus encoded latent
      membrane protein 1 in nasopharyngeal carcinoma cells via NF-kappaB and AP-1
      pathways.
AB  - B lymphocytes are generally considered to be the only source of immunoglobulins.
      However, increasing evidence revealed that some human epithelial cancer cell
      lines, including nasopharyngeal carcinoma (NPC) cell lines, expressed
      immunoglobulins. Moreover, we previously found that expression of kappa light
      chain in NPC cells could be upregulated by EBV-encoded latent membrane protein 1
      (LMP1). Here, Western blot and flow cytometric analysis of intracellular kappa
      staining indicated that upregulation of the expression of kappa was inhibited by
      using LMP1-targeted DNAzyme and that Bay11-7082 and SP600125, inhibitors of JNK
      and NF-kappaB, respectively, inhibited LMP1-augmented kappa light chain
      expression in NPC cells. LMP1-positive NPC cells expressing the dominant-negative
      mutant of IkappaBalpha (DNMIkappaBalpha) or of c-Jun (TAM67) exhibited
      significantly decreasing kappa production compared with their parental cells.
      These results suggest that LMP1 elevated kappa light chain through activation of
      the NF-kappaB and AP-1 signaling pathways. The present study provided some hints
      of possible mechanisms by which human cancer cells of epithelial origin produced
      immunoglobulins.

PMID- 16979874
TI  - Prevalence of undernutrition in elderly patients hospitalized in a geriatric unit
      in Belo Horizonte, MG, Brazil.
AB  - OBJECTIVES: We evaluated, from anthropometric and biochemical indicators, the
      prevalence of undernutrition within an elderly population hospitalized in Belo
      Horizonte, Minas Gerais, Brazil, and identified social demographic, clinical and
      biochemical factors associated with undernutrition. METHODS: A transverse
      sectional study involving 197 elderly patients was conducted. Anthropometric data
      were obtained from subjects directly or indirectly; clinical characteristics,
      including health problems, functional and cognitive abilities, and use of
      medication, were gathered from medical records; social demographic information
      was acquired by interviewing the subject or carer. Logistic regression analysis
      was employed to identify factors associated with undernutrition. RESULTS:
      According to the body mass index cutoff points recommended by the World Health
      Organization, 29.7% of subjects were classified as undernourished and 43.8% as
      eutrophic. Application of the Nutrition Screening Initiative system gave rise to
      an inverse situation in which 54.7% of subjects were considered undernourished
      and only 29.2% were eutrophic. Statistical analysis of the studied variables
      showed that calf circumference < or =31 cm was significantly associated with
      undernutrition (P < 0.0001) irrespective of the classification system employed,
      and may thus be considered a strong marker for undernutrition. In contrast, total
      serum cholesterol level > or =4.14 mmol/L was identified as a protective factor
      against undernutrition (P = 0.01). CONCLUSION: The prevalence of undernutrition
      among the hospitalized elderly in Brazil is very high. The measurement of calf
      circumference is a non-invasive and economical approach that can facilitate
      evaluation of the nutritional status of elderly individuals.

PMID- 16979875
TI  - Evidence for reprogramming global gene expression during zinc deficiency in the
      HUT-78 cell line.
AB  - OBJECTIVE: Investigations using cell lines, primary cells, animal models, and
      human subjects have provided data to indicate that zinc-deficient conditions
      affect immune functioning of myeloid and lymphoid cells. We hypothesized that
      zinc-deficient conditions alone may induce the expression of genes in lymphoid
      cells, which favor enhanced responses to myeloid molecules even in the absence of
      myeloid cells or myeloid factors. Our objective was to investigate the effects of
      low zinc-induced alterations in gene expression in a single lymphoid cell line in
      the absence of influences from growth factors and/or cytokines generated by other
      cell types also being affected by low zinc status. METHODS: Microarray analysis
      of non-stimulated and phytohemagglutinin-p/phorbol 12-myristate 13-acetate
      stimulated zinc-deficient and zinc-adequate human-derived HUT-78 (TH(0))
      lymphoblasts was used to identify changes in gene expressions associated solely
      with zinc-deficient status in these cells. RESULTS: Overall, gene expression for
      molecules that would increase T-lymphocyte response to signals from myeloid cells
      such as cytokine receptors and selected adhesion molecules were upregulated,
      whereas those associated with T-lymphocyte-directed immune functions, interleukin
      2 and interleukin-6 receptors, the cytokine interleukin-4, and zinc finger
      transcription factors were downregulated. Analysis of selected data obtained from
      healthy, but mildly zinc-deficient human subjects corroborated observations
      obtained from low zinc-altered gene expression in HUT-78 cells. CONCLUSION: These
      data provide evidence for a shift in gene expression of molecules that would
      increase lymphoid responses to myeloid driven pathways during periods of zinc
      deficiency even in the absence of myeloid-derived stimuli.

PMID- 16979876
TI  - Self-face recognition and theory of mind in patients with schizophrenia and first
      degree relatives.
AB  - OBJECTIVE: The hypothesized relationship between theory of mind (ToM) and self
      face recognition as well as its potential genetic associations has not been
      previously explored in patients with schizophrenia and in first-degree relatives
      with schizotypal personality traits. METHOD: Ten patients diagnosed with
      schizophrenia, 10 of their first-degree relatives and 10 healthy controls were
      included. To assess self-face recognition (SFR), participants were presented
      images of faces of themselves and others and asked to make rapid 'unfamiliar',
      'familiar' and 'self' judgments. As a measure of ToM, subjects were administered
      the Revised Mind in the Eyes Test (MET [Baron-Cohen, S., Wheelwright, S., Hill,
      J., Raste, Y., and Plumb, I., 2001. The "Reading the Mind in the Eyes" Test
      revised version: a study with normal adults, and adults with Asperger syndrome or
      high-functioning autism. J Child Psychol Psychiatry 42(2), 241-251.]).
      Schizotypal characteristics in relatives and controls were assessed using a
      modified version of the Schizotypal Personality Questionnaire (SPQ [Raine, A.,
      1991. The SPQ: a scale for the assessment of schizotypal personality based on DSM
      III-R criteria. Schizophrenia Bulletin 17(4), 555-564.]). RESULTS: Patients took
      longer and were less accurate on the SFR task than their relatives who in turn
      performed worse than healthy controls. Specific ToM deficits in schizophrenia
      were replicated. There was a relationship between accuracy rates on the MET and
      SFR tasks. High levels of schizotypal traits such as social anxiety, constricted
      affect and no close friends were important for both tasks. CONCLUSIONS: Face
      recognition deficits and ToM deficits in schizophrenia are apparent. The critical
      influence of high levels of select schizotypal traits is also highlighted. A
      deficit in relatives of schizophrenia patients raises the possibility that ToM
      and face recognition deficits may be candidate endophenotypes for schizophrenia.
      Support for the hypothesized link between ToM and face recognition is provided.

PMID- 16979877
TI  - Efficacy of the combination of levofloxacin plus ceftazidime in the treatment of
      hospital-acquired pneumonia in the intensive care unit.
AB  - To investigate the efficacy and tolerability of treatment with a combination of
      levofloxacin and ceftazidime in Gram-negative hospital-acquired pneumonia (HAP)
      in the Intensive Care Unit (ICU), we performed a prospective, open-label, non
      comparative, 1-year study in an Italian ICU. Patients received levofloxacin 500
      mg twice a day intravenously plus ceftazidime 2 g three times a day intravenously
      for 7-14 days. Primary efficacy variables were clinical and microbiological
      responses at test-of-cure visit. Twenty-one patients were enrolled. Pseudomonas
      aeruginosa and Klebsiella pneumoniae were the most frequently identified
      pathogens. Clinical success was achieved in 17/21 clinically evaluable patients
      (81%) and in 12/15 microbiologically evaluable patients (80%). Regarding only the
      group with ventilator-associated pneumonia, cure was achieved in 10/14 clinically
      evaluable patients (71%) and in 11/14 microbiologically evaluable patients (79%).
      Therapy was well tolerated. We conclude that this combination regimen is safe and
      clinically and microbiologically efficacious in the treatment of Gram-negative
      HAP.

PMID- 16979878
TI  - Fiber type-specific immunostaining of the Na+,K+-ATPase subunit isoforms in
      skeletal muscle: age-associated differential changes.
AB  - The expression of the Na(+),K(+)-ATPase alpha and beta subunit isoforms in rat
      skeletal muscle and its age-associated changes have been shown to be muscle-type
      dependent. The cellular basis underlying these findings is not completely
      understood. In this study, we examined the expression of Na(+),K(+)-ATPase
      isoforms in individual fiber types and tested the hypothesis that, with age, the
      changes in the expression of the isoforms differ among individual fibers. We
      utilized immunohistochemical techniques to examine the expression of the subunit
      isoforms at the individual fiber levels. Immunofluorescence staining of the
      subunit isoforms in both white gastrocnemius (GW) and red gastrocnemius (GR)
      revealed a predominance of staining on the sarcolemmal membrane. Compared to the
      skeletal muscle of 6-month-old rats, there were substantial increases in the
      levels of alpha1, beta1, and beta3 subunit isoforms, and decreases in the levels
      of alpha2 and beta2 in 30-month-old rats. In addition, we found distinct patterns
      of staining for the alpha1, alpha2, beta1, and beta2 isoforms in tissue sections
      from young and aged rats. Muscle fiber-typing was performed to correlate the
      pattern of staining with specific fiber types. Staining for alpha1 and alpha2
      isoforms in the skeletal muscle of young rats was generally evenly distributed
      among the fibers of GW and GR, with the exception of higher alpha1 levels in slow
      twitch oxidative Type I fibers of GR. By contrast, staining for the beta1 and
      beta2 isoforms in the mostly oxidative fibers and the mostly glycolytic fibers,
      respectively, was almost mutually exclusive. With age, there was a fiber-type
      selective qualitative decrease of alpha2 and beta2 in Type IIB fibers, and
      increase of beta1 in Type IIB fibers and beta2 in Type IID fibers of white
      gastrocnemius. These results provide, at the individual fiber level, a cellular
      basis for the differential expression of the Na(+),K(+)-ATPase subunit isoforms
      in the muscle groups. The data further indicate that the aged-associated changes
      in expression of the subunit isoforms occur in both a fiber-type specific as well
      as an across fiber-type manner. Because of the differing biochemical properties
      of the subunit isoforms, these changes add another layer of complexity in our
      understanding of the adaptation of the Na-pump in skeletal muscle with advancing
      age.

PMID- 16979880
TI  - XMam1, Xenopus Mastermind1, induces neural gene expression in a Notch-independent
      manner.
AB  - Mastermind, which is a Notch signal component, is a nuclear protein and is
      thought to contribute to the transactivation of target genes. Previously we
      showed that XMam1, Xenopus Mastermind1, was essential in the transactivation of a
      Notch target gene, XESR-1, and was involved in primary neurogenesis. To examine
      the function of XMam1 during Xenopus early development in detail, XMam1
      overexpressed embryos were analyzed. Overexpression of XMam1 ectopically caused
      the formation of a cell mass with pigmentation on the surface of embryos and
      expressed nrp-1. The nrp-1-positive cell mass was produced by XMam1 without
      expression of the Notch target gene, XESR-1, and not by the activation form of
      Notch, NICD. The ectopic expression of nrp-1 was not inhibited by co-injection of
      XMam1 with a molecule known to inhibit Notch signaling. The nrp-1 expression was
      also recognized in the animal cap injected with XMam1DeltaN, which lacks the
      basic domain necessary for interacting with NICD and Su(H). These results show
      that XMam1 has the ability to induce the cell fate into the neurogenic lineage in
      a Notch-independent manner.

PMID- 16979881
TI  - Ultrasonic characterization of proteins and blood cells.
AB  - Ultrasound changes its intensity and speed when propagating through a liquid or a
      suspension containing particles. In addition it generates a weak electric signal
      by altering the motion of ions and charged particles. Hence acoustic and
      electroacoustic measurements provide information about the properties of
      suspended particles and molecules. Here we present both acoustic and
      electroacoustic results on blood suspensions and protein solutions, relevant to
      life sciences. For blood cells a strong increase in acoustic attenuation with
      volume fraction is found, from which the speed of sound in an erythrocyte is
      found to be about 1900 m/s, assuming the attenuation is due to scattering only. A
      similar value of 1700 m/s is found from the increase in sound speed of the
      dispersion with concentration. Electroacoustic measurements on bovine serum
      albumin (BSA) yield a charge of about seven elementary charges per BSA molecule.
      These results show the power and usefulness of acoustic and electroacoustic
      measurement techniques for biological systems.

PMID- 16979882
TI  - [Pregnancy during primary hypothyroidism].

PMID- 16979883
TI  - Automated detection of qualitative spatio-temporal features in electrocardiac
      activation maps.
AB  - OBJECTIVE: This paper describes a piece of work aiming at the realization of a
      tool for the automated interpretation of electrocardiac maps. Such maps can
      capture a number of electrical conduction pathologies, such as arrhytmia, that
      can be missed by the analysis of traditional electrocardiograms. But, their
      introduction into the clinical practice is still far away as their interpretation
      requires skills that belongs to very few experts. Then, an automated
      interpretation tool would bridge the gap between the established research outcome
      and clinical practice with a consequent great impact on health care. METHODS AND
      MATERIAL: Qualitative spatial reasoning can play a crucial role in the
      identification of spatio-temporal patterns and salient features that characterize
      the heart electrical activity. We adopted the spatial aggregation (SA) conceptual
      framework and an interplay of numerical and qualitative information to extract
      features from epicardial maps, and to make them available for reasoning tasks.
      RESULTS: Our focus is on epicardial activation isochrone maps as they are a
      synthetic representation of spatio-temporal aspects of the propagation of the
      electrical excitation. We provide a computational SA-based methodology to
      extract, from 3D epicardial data gathered over time, (1) the excitation wavefront
      structure, and (2) the salient features that characterize wavefront propagation
      and visually correspond to specific geometric objects. CONCLUSION: The proposed
      methodology provides a robust and efficient way to identify salient pieces of
      information in activation time maps. The hierarchical structure of the abstracted
      geometric objects, crucial in capturing the prominent information, facilitates
      the definition of general rules necessary to infer the correlation between
      pathophysiological patterns and wavefront structure and propagation.

PMID- 16979884
TI  - C-reactive protein in hypertension: clinical significance and predictive value.
AB  - Mild elevations in C-reactive protein concentration predict myocardial
      infarction, stroke, and vascular death in a variety of clinical settings. Despite
      the lack of specific evidence that C-reactive protein levels are independently
      associated with cardiovascular risk in patients with hypertension, the prognostic
      value of C-reactive protein has proven to be complementary to that of blood
      pressure values. Recent epidemiological evidence has indicated a link between
      hypertension and increased C-reactive protein levels, and there are some
      indications that C-reactive protein may predict the future development of
      hypertension. Vessel wall inflammation is part of the vascular changes observed
      in animal models of hypertension. C-reactive protein is involved in the complex
      pathways leading to endothelial dysfunction, increased peripheral vascular
      resistance, and large artery stiffness in hypertension. In this regard, the role
      of C-reactive protein as a marker or a causal factor in promoting hypertension
      and its complications remains, however, to be elucidated. In this review, various
      aspects of the pathogenesis of inflammation in hypertension are summarized and
      connected with clinical studies that address the role of C-reactive protein in
      hypertensive disease.

PMID- 16979885
TI  - SLRP interaction can protect collagen fibrils from cleavage by collagenases.
AB  - Decorin, fibromodulin and lumican are small leucine-rich repeat proteoglycans
      (SLRPs) which interact with the surface of collagen fibrils. Together with other
      molecules they form a coat on the fibril surface which could impede the access to
      collagenolytic proteinases. To address this hypothesis, fibrils of type I or type
      II collagen were formed in vitro and treated with either collagenase-1 (MMP1) or
      collagenase-3 (MMP13). The fibrils were either treated directly or following
      incubation in the presence of the recombinant SLRPs. The susceptibility of the
      uncoated and SLRP-coated fibrils to collagenase cleavage was assessed by
      SDS/PAGE. Interaction with either recombinant decorin, fibromodulin or lumican
      results in decreased collagenase cleavage of both fibril types. Thus SLRP
      interaction can help protect collagen fibrils from cleavage by collagenases.

PMID- 16979886
TI  - A disposable on-chip phosphate sensor with planar cobalt microelectrodes on
      polymer substrate.
AB  - Disposable microsensors on polymer substrates consisting of fully integrated on
      chip planar cobalt (Co) microelectrodes, Ag/AgCl reference electrodes, and
      microfluidic channels have been designed, fabricated, and characterized for
      phosphate concentration measurement in aqueous solution. The planar Co
      microelectrode shows phosphate-selective potential response over the range from
      10(-5) to 10(-2)M in acidic medium (pH 5.0) for both inorganic (KH(2)PO(4)) and
      organic (adenosine 5'-triphosphate (ATP) and adenosine 5'-diphosphates (ADP))
      phosphate compounds. This microfabricated sensor also demonstrates significant
      reproducibility with a small repeated sensing deviation (i.e. relative standard
      deviation (R.S.D.)<1%) on a single chip and a small chip-to-chip deviation (i.e.
      R.S.D.<2.5%). Specifically, while keeping the high selectivity, sensitivity, and
      stability of a conventional bulk Co-wire electrode, the proposed phosphate sensor
      yields advantages such as ease of use, cost effectiveness, reduced analyte
      consumption, and ease of integrating into disposable polymer lab-on-a-chip
      devices. The capability to sense both inorganic and organic phosphate compounds
      makes this sensor applicable in diverse areas such as environmental monitoring,
      soil extract analysis, and clinical diagnostics.

PMID- 16979887
TI  - Applications of ultrasound streaming and radiation force in biosensors.
AB  - Direct radiation force (DRF) and acoustic streaming provide the main influences
      on the behaviour of particles in aqueous suspension in an ultrasound standing
      wave (USW). The direct radiation force, which drives suspended particles towards
      and concentrates them in acoustic pressure node planes, has been applied to
      rapidly transfer cells in small scale analytical separators. The DRF also
      significantly increased the sensitivity of latex agglutination test (LAT) by
      concentrating the particles of an analytical sample in the pressure node
      positions and hence greatly increasing the antibody-antigen encounter rate.
      Capture of biotinylated particles and spores on a coated acoustic reflector in a
      quarter wavelength USW resonator was DRF-enhanced by 70- and 100-fold,
      respectively compared to the situation in the absence of ultrasound. Acoustic
      streaming has been successfully employed for mixing small analytical samples.
      Cavitation micro-streaming substantially enhanced, through mixing, DNA
      hybridization and the capture efficiency of Escherichia coli K12 on the surface
      of immunomagnetic beads. Acoustic streaming induced in longitudinal standing wave
      and flexural plate wave immuno-sensors increased the detection of antigens by a
      factor of five and three times, respectively. Combined DRF and acoustic streaming
      effects enhanced the rate of the reaction between suspended mixture of cells and
      retroviruses. The examples of a biochip and an ultrasonic immuno-sensor
      implementing the DRF and acoustic streaming effects are also described in the
      review.

PMID- 16979888
TI  - Variation in relative survival of thyroid cancers in Europe: results from the
      analysis on 21 countries over the period 1983-1994 (EUROCARE-3 study).
AB  - We described the relative survival of thyroid cancer cases diagnosed in Europe
      during the period 1990-1994 and analysed time trends in relative survival during
      the period 1983-1994 using the EUROCARE-3 database. Relative survival of thyroid
      cancers is one of the highest amongst cancer sites, with age-standardised
      relative survival rates of 74% in men and 82% in women over the period 1990-1994,
      with marked differences between countries. The higher relative survival rates are
      observed in Scandinavian countries and the lower rates are observed in the UK and
      the countries of Eastern Europe. Relative survival is higher in women than in
      men, and decreases with age whatever the histological group. There are
      significant differences in relative survival according to histological type.
      Relative survival has slightly increased over the period 1983-1994 only when all
      histological types have been considered together. Time trend was, however, non
      existent when the different histological groups were taken into account except
      during the most recent period of observation. One possible explanation for the
      differences in relative survival between countries and sex may probably be found
      in the changes in thyroid classification and diagnosis techniques. When these
      changes are not homogeneous, the distribution of thyroid cancers by histology and
      by stage at diagnosis may be very different. The only way to understand these
      differences is to conduct specific studies including a description of stage at
      diagnosis, diagnosis procedures used for staging and details of treatment.

PMID- 16979889
TI  - Gene expression profile analysis of an isogenic tumour metastasis model reveals a
      functional role for oncogene AF1Q in breast cancer metastasis.
AB  - To study the molecular mechanisms underlying breast cancer metastasis, gene
      expression profile analysis was performed on two well-established breast cancer
      cell lines with high and low metastatic potentials: MDA-MB-435HM and MDA-MB
      435LM. The analysis was conducted using cDNA microarrays containing 8000 genes.
      Of 60 differentially expressed genes, ALL1-fused gene from chromosome 1q (AF1Q),
      a putative oncogene not described previously in breast cancer, was identified and
      found to be over-expressed in MDA-MB-435HM cells compared with MDA-MB-435LM
      cells. The results indicate that AF1Q may play an important role in breast cancer
      metastasis. To test this hypothesis, we generated an AF1Q high-expression cell
      line by stable transfection of AF1Q cDNA into MDA-MB-435LM cells. Results showed
      that over-expression of AF1Q led to a marked increase in the invasive and
      metastatic potential of MDA-MB-435LM cells in vitro and in vivo, accompanied by
      the up-regulation of matrix metalloproteinase-2 (MMP-2), MMP-9, transcription
      factor Ets-1, and RhoC expression in both mRNA and protein levels. Consistent
      with this observation, reduced AF1Q expression in MDA-MB-435HM cells by small
      interfering RNA (siRNA) resulted in a significant decrease in the invasive
      potential of MDA-MB-435HM cells in vitro and in the protein expression of MMP-2,
      MMP-9, Ets-1, and RhoC, compared with either parental or non-silencing control
      cells. These data provide functional evidence that oncogene AF1Q may be a novel
      mediator of metastasis promotion in human breast cancer through regulation of the
      MMP pathway and RhoC expression.

PMID- 16979890
TI  - A nurse is a nurse? A systematic review of the effectiveness of specialised
      nursing in breast cancer.
AB  - The effectiveness of specialised nursing in breast cancer has received limited
      attention. This systematic literature review aims at (i) presenting and
      discussing role models of specialised nursing in the area of breast cancer and
      (ii) suggesting avenues for future research in this field. The ten studies
      included in the review differ with respect to the roles of specialised nurses as
      well as the measured outcome variables; thus, the comparability and
      generalisability of results are limited. Nevertheless, the review indicates that
      specialised nursing in breast cancer may contribute to improved physical and
      psycho-social well-being. In view of the limited comparability, the authors call
      for (i) a more uniform definition of models of specialised nursing in breast
      cancer care, as well as (ii) rigorous confirmatory studies to evaluate their
      effectiveness. These two aspects are pivotal in providing a reliable basis for
      future health care strategies.

PMID- 16979891
TI  - Inequalities in oncology care: Economic consequences of high cost drugs.
AB  - The expenditures for hospital drugs are continuously increasing, and grow much
      faster than the global hospital budgets do. This explosive growth is caused
      mainly by a few so-called 'expensive drugs' of which the oncolytics form the main
      part. The global budgets should stimulate more effective provision of care
      ('technical efficiency'), however the room for technical efficiency is
      decreasing. Hospitals thus have to make impossible choices, so that eventually
      equal access can no longer be guaranteed. If no other policies are applied,
      health care goals will no longer be met. This paper tries to map the contours of
      the current problem and its possible solutions. It is time governments take up
      their responsibility and take back control.

PMID- 16979892
TI  - Biochemical aromatization of 2-methyleneandrostenedione: stereochemistry of
      hydrogen removal at the C-1 position.
AB  - To explore a stereochemistry of hydrogen removal at C-1 of the powerful aromatase
      inhibitor 2-methyleneandrostenedione (1), of which the A-ring conformation is
      markedly different from that of the natural substrate androstenedione (AD), in
      the course of the aromatase-catalyzed A-ring aromatization producing 2
      methylestrone (2), we synthesized [1alpha-2H]labeled steroid 1 and its [1beta
      2H]stereoisomer, and the metabolic fate of the C-1 deuterium in aromatization was
      analyzed by gas chromatography-mass spectrometry (GC-MS) in each. Parallel
      experiments with the natural substrates [1alpha-2H] and [1beta-2H]ADs were also
      carried out. The GC-MS analysis indicated that 2-methyl estrogen 2 produced from
      [1alpha-2H]labeled substrate 1 retained completely the 1alpha-deuterium (1beta-H
      elimination), while product 2 obtained from [1beta-2H]isomer 1 lost completely
      the 1beta-deuterium. Stereospecific 1beta-hydrogen elimination was also observed
      in the parallel experiments with the labeled ADs as established previously. The
      results indicate that biochemical aromatization of the 2-methylene steroid 1
      proceeds through the 1beta-hydrogen removal concomitant with cleavage of the
      C(10)-C(19) bond, yielding 1(10),4-dienone 9, in a similar manner to that
      involved in AD aromatization. This would give additional evidence for the
      stereomechanisms for the last step of aromatization of AD, requiring the
      stereospecific 1beta-hydrogen abstraction and cleavage of the C(10)-C(19) bond,
      and for the enolization of a carbonyl group at C-3 in the A-ring aromatization.

PMID- 16979893
TI  - Ground reaction forces on stairs. Part II: knee implant patients versus normals.
AB  - The goal of this study was to compare selected parameters of vertical ground
      reaction forces (GRF) of good outcome patients with different prosthesis designs
      with a matched control group during level walking, stair ascent and descent.
      Forty subjects, 29 with three main implant designs (including four subjects with
      a passive knee flexion restriction), and 11 healthy controls were measured with 8
      10 repetitions. Vertical ground reaction forces were measured during two
      consecutive steps with force plates embedded in the walkway and the staircase.
      Defined parameters of the force signals were used to compare the results of the
      test groups. The results show, that, postoperatively, good outcome patients
      produce gait patterns of the vertical ground reaction force which are comparable
      to normal healthy subjects with the exception of a few distinct differences: a
      significant reduction (p<0.05) in the vertical loading on the operated side
      during level walking at take-off, at weight acceptance and take-off during stair
      ascent of the normal stair. During stair descent, the patients did not reduce
      load on the operated side, but increased load variation and side-to-side
      asymmetry; thus, the mechanical loads on the implants were high, which may be
      important information with respect to loading protocols of knee implant
      simulators. No systematic differences in any of the test parameters were found
      between posterior cruciate-retaining (LCS MB and Innex CR) versus non-retaining
      (LCS RP and Innex UCOR) implant designs. The restricted group showed significant
      reductions (p<0.05) of several loading parameters as well as an increased side-to
      side asymmetry. About one third of the force parameters of the good outcome
      patients showed a side-to-side asymmetry between two consecutive steps, which was
      over a proposed level of acceptance.

PMID- 16979894
TI  - Maturation of Golgi cisternae directly observed.
AB  - Newly synthesized secretory proteins pass through the Golgi apparatus, which
      consists of multiple cisternae containing distinct populations of enzymes. Are
      the cargo proteins shuttled between cisternae in vesicles or do they remain in a
      cisterna while it is the Golgi enzymes that are removed and replaced? As
      predicted by the latter model--the cisternal maturation hypothesis--two groups
      have directly observed the replacement of one Golgi protein with another in
      individual cisternae, thus answering the question. However, its solution raises
      many more unknowns.

PMID- 16979895
TI  - MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 6:
      exploration of aromatic substituents.
AB  - A series of 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives, derivatized at the 2
      position with aromatic substituents, were synthesized by the Suzuki cross
      coupling method and evaluated for their ability to potentiate the activity of the
      fluoroquinolone levofloxacin (LVFX) and the anti-pseudomonas beta-lactam
      aztreonam (AZT) in Pseudomonas aeruginosa. By incorporating hydrophilic
      substituents onto the aryl nucleus, we found a morpholine analogue that possessed
      improved solubility, retained activity in vitro, and displayed potentiation
      activity in vivo in a rat model of P. aeruginosa pneumonia.

PMID- 16979896
TI  - New bisanthraquinone antibiotics and semi-synthetic derivatives with potent
      activity against clinical Staphylococcus aureus and Enterococcus faecium
      isolates.
AB  - The escalation of antibiotic resistance among Gram-positive pathogens presents
      increasing treatment challenges and requires the development of innovative
      therapeutic agents. Here, we present the antimicrobial properties of structurally
      unusual bisanthraquinone metabolites produced by a marine streptomycete and four
      semi-synthetic derivatives. Biological activities were measured against
      clinically derived isolates of vancomycin-resistant Enterococcus faecium (VRE),
      and methicillin-susceptible, methicillin-resistant, and tetracycline-resistant
      Staphylococcus aureus (MSSA, MRSA, and TRSA, respectively). The most potent
      antibiotic displayed MIC(50) values of 0.11, 0.23, and 0.90microM against a panel
      (n=25 each) of clinical MSSA, MRSA, and VRE, respectively, and was determined to
      be bactericidal by time-kill analysis.

PMID- 16979897
TI  - A standard protocol for obtaining fish chromosomes under post-mortem conditions.
AB  - In order to improve cytogenetical analyses on fish, especially focusing on
      delicate and rare species, we have adopted a new in vitro methodology using dead
      animals. The results obtained from 24 neotropical freshwater and marine fish
      species demonstrate that chromosomes can be obtained under post-mortem
      conditions. Significantly, the samples analyzed provided reliable cytogenetical
      data in nearly all cases. Other advantages of this new methodology are also
      discussed.

PMID- 16979898
TI  - Recurrent hyperparathyroidism: A sixth mediastinal parathyroid gland.
AB  - We present the case of a 71-year-old woman with recurrent hyperparathyroidism.
      She underwent first a subtotal resection of the parathyroid glands associated
      with subtotal thyroidectomy in the setting of primary hyperparathyroidism and
      multi nodular thyroid. Pathologic findings were consistent with hyperplasia and
      demonstrated a fifth parathyroid gland in the thyroid. Two years later, the
      patient presented recurrent hyperparathyroidism associated with terminal renal
      insufficiency, fusion of Sesta Mibi scintigraphy and CT scan demonstrated a sixth
      mediastinal parathyroid gland in the aorto pulmonary window. Despite
      videomediastinoscopic attempts, resection was performed through manubriotomy
      approach. Pathologic findings demonstrated a parathyroid adenoma.

PMID- 16979899
TI  - Phenothiazinium derivatives for pathogen inactivation in blood products.
AB  - Phenothiazine-based photosensitisers have been employed in photoantimicrobial
      research for nearly 80 years, both as lead and novel compounds. However, the main
      structural variations have mainly involved the auxochromic side chains and little
      has been reported concerning either peripheral substitution or structures with
      chromophores other than those of the phenothiazinium or annelated
      benzo[a]phenothiazinium type. In terms of application, the phenothiazinium series
      has featured commonly in cytology and cytopathology, as well as in haematological
      staining. The current work covers the evolution of improved photosensitisers
      based on the phenothiazine ring system, with particular reference to the field of
      pathogen inactivation, and the structural alteration of lead compounds such as
      methylene blue and Nile blue to yield improved photosensitisers for this
      important aspect of blood product safety.

PMID- 16979900
TI  - Does transforming growth factor-beta1 predict for radiation-induced pneumonitis
      in patients treated for lung cancer?
AB  - The purpose of the study was to reassess the utility of transforming growth
      factor-beta-1 (TGF-beta1) together with dosimetric and tumor parameters as a
      predictor for radiation pneumonitis (RP). Of the 121 patients studied, 32 (26.4%)
      developed grade > or =1 RP, and 27 (22.3%) developed grade > or =2 RP. For the
      endpoint of grade > or =1 RP, those with V30>30% and an end-RT/baseline TGF-beta1
      ratio> or =1 had a significantly higher incidence of RP than did those with
      V30>30% and an end-RT/baseline TGF-beta1 ratio<1. For most other patient groups,
      there were no clear associations between TGF-beta1 values and rates of RP. These
      findings suggest that TGF-beta1 is generally not predictive for RP except for the
      group of patients with a high V30.

PMID- 16979901
TI  - Folding and assembly of hemoglobin monitored by electrospray mass spectrometry
      using an on-line dialysis system.
AB  - The native structure of hemoglobin (Hb) comprises two alpha- and two beta
      subunits, each of which carries a heme group. There appear to be no previous
      studies that report the in vitro folding and assembly of Hb from highly unfolded
      alpha- and beta-globin in a "one-pot" reaction. One difficulty that has to be
      overcome for studies of this kind is the tendency of Hb to aggregate during
      refolding. This work demonstrates that denaturation of Hb in 40% acetonitrile at
      pH 10.0 is reversible. A dialysis-mediated solvent change to a purely aqueous
      environment of pH 8.0 results in Hb refolding without any apparent aggregation.
      Fluorescence, Soret absorption, circular dichroism, and ESI mass spectra of the
      protein recorded before unfolding and after refolding are almost identical. By
      employing an externally pressurized dialysis cell that is coupled on-line to an
      ESI mass spectrometer, changes in heme binding behavior, protein conformation,
      and quaternary structure can be monitored as a function of time. The process
      occurs in a stepwise sequential manner, leading from monomeric alpha- and beta
      globin to heterodimeric species, which then assemble into tetramers. Overall,
      this mechanism is consistent with previous studies employing the mixing of folded
      alpha- and beta-globin. However, some unexpected features are observed, e.g., a
      heme-deficient beta-globin dimer that represents an off-pathway intermediate.
      Monomeric beta-globin is capable of binding heme before forming a complex with an
      alpha-subunit. This observation suggests that holo-alpha-apo-beta globin does not
      represent an obligatory intermediate during Hb assembly, as had been proposed
      previously. The on-line dialysis/ESI-MS approach developed for this work
      represents a widely applicable tool for studying the folding and self-assembly of
      noncovalent biological complexes.

PMID- 16979902
TI  - Sub parts-per-million mass measurement accuracy of intact proteins and product
      ions achieved using a dual electrospray ionization quadrupole fourier transform
      ion cyclotron resonance mass spectrometer.
AB  - High mass measurement accuracy (MMA) is demonstrated for intact proteins and
      subsequent collision-induced dissociation product ions using internal
      calibration. Internal calibration was accomplished using a dual electrospray
      ionization source coupled with a hybrid quadrupole Fourier transform ion
      cyclotron resonance (Q-FT-ICR) mass spectrometer. Initially, analyte ions
      generated via the first electrospray (ESI) emitter are isolated and dissociated
      in the external quadrupole. This event is followed by a simultaneous switch to
      the calibrant ion ESI emitter and a disablement of the isolation and activation
      of the external quadrupole such that a broad m/z range of calibrant ions are
      accumulated before injecting the analyte/calibrant ion mixture into the ICR cell.
      Two different internal calibrant solutions were utilized in these studies to
      evaluate this approach for the top-down characterization of melittin and
      ubiquitin. While external calibration of protein fragments resulted in absolute
      MMA greater than 16 ppm, internal standardization significantly improved upon the
      MMA of both the intact proteins and their products ions which ranged from -2.0
      ppm to 1.1 ppm, with an average of -0.9 ppm. This method requires limited
      modification to ESI-FT-ICR mass spectrometers and is applicable for both positive
      and negative ionization modes.

PMID- 16979903
TI  - In vivo inactivation of pRb, p107 and p130 in murine neuroprogenitor cells leads
      to major CNS developmental defects and high seizure rates.
AB  - Nestin-positive cells were targeted for pRb, p107 and p130 (pRb(f)) inactivation
      by expression of T(121), a truncated SV40 large T antigen that selectively binds
      to and inactivates pRb(f). Cre expression was initiated under GFAP control,
      resulting in T(121) expression restricted to neuroprogenitor cells beginning at
      embryonic day 11.5 (E11.5). Bi-transgenic embryos showed aberrant central nervous
      system (CNS) cell proliferation and apoptosis by E13.5. Defects in cortical
      development were evident with primary effects resulting in depletion of neural
      progenitors and aberrant cellular migration. Consequently, juvenile and adult
      brain morphology was reproducibly abnormal, including disorganization of
      neocortical, hippocampal and cerebellar regions. These aberrations resulted in
      behavioral phenotypes, including ataxia and seizures. The data indicate that
      inactivation of pRb(f) in radial glial cells, a population of neuroprogenitor
      cells, leads to specific disruptions in CNS patterning. The neuroprogenitor
      restricted transgene expression provides a model in which to explore both
      developmental mechanisms and functional neurological outcomes.

PMID- 16979904
TI  - Comparison of the effects of 2,2,2-trifluoroethanol on peptide and protein
      structure and function.
AB  - The co-solvent 2,2,2-trifluoroethanol (TFE) has been often used to aid formation
      of secondary structure in solution peptides or alternately as a denaturant within
      protein folding studies. Hen egg white lysozyme (HEWL) and a synthetic model
      peptide defining HEWL helix-4 were used as comparative model systems to
      systematically investigate the effect of increasing TFE concentrations on the
      structure of proteins and peptides. HEWL was analyzed using NMR, far-UV CD and
      fluorescence spectroscopy; with correlation of these results towards changes in
      enzymatic activity and the helix-4 peptide was analysed using NMR. Data
      illustrates two conflicting modes of interaction: Low TFE concentrations
      stabilize tertiary structure, observed from an increase in the number of NMR NOE
      contacts. Higher TFE concentrations denatured HEWL with the loss of lysozyme
      tertiary structure. The effects of TFE upon secondary structural elements within
      HEWL are distinct from those observed for the helix-4 peptide. This illustrates a
      dissimilar interaction of TFE towards both protein and peptide at equivalent TFE
      concentrations. The concentration that TFE promotes stabilization over
      denaturation is likely to be protein dependent although the structural action can
      be extrapolated to other protein systems with implications for the use of TFE in
      structural stability studies.

PMID- 16979905
TI  - A molecular dynamics analysis of the GCC-box binding domain in ethylene
      responsive element binding factors.
AB  - Ethylene-responsive element (ERE) binding factors is responsible for a consensus
      nucleotide sequence AGCCGCC (GCC-box) binding in many important process of plant
      growing through gene regulation and mediating signal transduction pathways in
      response to environmental stress. The GCC-box binding domain (GBD) as a novel
      fold for DNA recognition has been analyzed by means of molecular dynamics. The
      simulations show that the complex of GBD-DNA trajectories show similar
      fluctuations in the atomic positions as uncomplexed, particularly at three beta
      strands involving DNA binding. The calculations of entropy also affirm that GBD
      flexibility is basically similar for two ligation states. Further, the two
      complexation states present similar patterns of concerted motions, indicating
      that the bound DNA cannot alter GBD flexibility. It is inferred that the
      flexibility of GBD molecule is independent of its ligation state. So in the
      protein-DNA recognition, the GBD cannot be easily induced while DNA shows better
      flexibility. Comparison between simulations of unligated GBD and the complexed
      GBD (in isolation or DNA-bound) reveals intrinsic flexibilities in some certain
      parts of the molecule play a key role in DNA recognition. In addition, MD
      simulation identifies that water molecule may mediate interaction between GBD and
      DNA.

PMID- 16979906
TI  - Ab initio random model method facilitates 3D reconstruction of icosahedral
      particles.
AB  - Model-based, three-dimensional (3D) image reconstruction procedures require a
      starting model to initiate data analysis. We have designed an ab initio method,
      which we call the random model (RM) method, that automatically generates models
      to initiate structural analysis of icosahedral viruses imaged by cryo-electron
      microscopy. The robustness of the RM procedure was demonstrated on experimental
      sets of images for five representative viruses. The RM method also provides a
      straightforward way to generate unbiased starting models to derive independent 3D
      reconstructions and obtain a more reliable assessment of resolution. The
      fundamental scheme embodied in the RM method should be relatively easy to
      integrate into other icosahedral software packages.

PMID- 16979907
TI  - Two-dimensional crystallization of human vitamin K-dependent gamma-glutamyl
      carboxylase.
AB  - Planar-tubular two-dimensional (2D) crystals of human vitamin K-dependent gamma
      glutamyl carboxylase grow in the presence of dimyristoyl phosphatidylcholine
      (DMPC). Surprisingly, these crystals form below the phase transition temperature
      of DMPC and at the unusually low molar lipid-to-protein (LPR) ratio of 1, while
      2D crystals are conventionally grown above the phase transition temperature of
      the reconstituting lipid and significantly higher LPRs. The crystals are up to
      0.75 microm in the shorter dimension of the planar tubes and at least 1 microm in
      length. Due to the planar-tubular nature of the crystals, two lattices are
      present. These are rotated by nearly 90 degrees in respect to each other. The
      ordered arrays exhibit p12(1) plane group symmetry with unit cell dimensions of
      a=83.7 A, b=76.6 A, gamma=91 degrees. Projection maps calculated from images of
      negatively stained and electron cryo-microscopy samples reveal the human vitamin
      K-dependent gamma-glutamyl carboxylase to be a monomer.

PMID- 16979908
TI  - Solution structure of amphibian tachykinin Uperolein bound to DPC micelles.
AB  - Uperolein, a physalaemin-like endecapeptide, has been shown to be selective for
      Neurokinin 1 receptor. As a first step towards understanding the structure
      activity relationship, we report the membrane-induced structure of Uperolein with
      the aid of circular dichroism and 2D (1)H NMR spectroscopy. Sequence-specific
      resonance assignments of protons have been made using correlation spectroscopy
      (TOCSY, DQF-COSY) and NOESY spectroscopy. The interproton distance constraints
      and dihedral angle constraints have been utilized to generate a family of
      structures using torsion angle molecular dynamics within program DYANA. The
      conformational range of the peptide revealed by NMR and CD studies has been
      analysed in terms of characteristic secondary features. Analysis of NMR data
      indicates that the global fold of Uperolein can be explained in terms of
      equilibrium between 3(10)-helix and alpha-helix from residues 5 to 11. An
      extended highly flexible N-terminus displays some degree of order and a possible
      turn structure. A comparison between the structures of Uperolein and Substance P,
      a prototype and endogenous Neurokinin 1 receptor agonist, indicates several
      common features in the distribution of hydrophobic and hydrophilic residues. Both
      the peptides show an amphiphilic character towards the middle region. The
      similarities suggest that the molecules interact with the receptor in an
      analogous manner.

PMID- 16979909
TI  - Behavioral Inhibition System activity is associated with increased amygdala and
      hippocampal gray matter volume: A voxel-based morphometry study.
AB  - Recent research has examined anxiety and hyperactivity in the amygdala and the
      anterior hippocampus while processing aversive stimuli. In order to determine
      whether these functional differences have a structural basis, optimized voxel
      based morphometry was used to study the relationship between gray matter
      concentration in the brain and scores on a Behavioral Inhibition System measure
      (the Sensitivity to Punishment scale) in a sample of 63 male undergraduates.
      Results showed a positive correlation between Sensitivity to Punishment scores
      and gray matter volume in the amygdala and the hippocampal formation, that is, in
      areas that Gray, J.A., and McNaughton, N.J. (2000). The neuropsychology of
      anxiety. Oxford: Oxford Medical Publications. associated with the Behavioral
      Inhibition System.

PMID- 16979910
TI  - Fast structural brain imaging using an MDEFT sequence with a FLASH-EPI hybrid
      readout.
AB  - A sequence for the fast acquisition of T1 weighted structural brain images with
      whole brain coverage and isotropic resolution of 1mm is presented. It is based on
      MDEFT with a FLASH-EPI hybrid readout. Several techniques for artefact
      suppression are implemented, like echo time shifting, asymmetric k-space
      sampling, and navigator echo acquisition. It is shown experimentally that the
      hybrid MDEFT sequence with a total duration of 8min yields approximately the same
      signal-to-noise and contrast-to-noise ratios as a 12min standard MDEFT sequence
      based on a FLASH readout. Further experiments show that echo time shifting
      suppresses artefacts in the vicinity of the scalp and in areas suffering from
      field inhomogeneities and that the concept of asymmetric k-space sampling reduces
      the susceptibility to head movement.

PMID- 16979912
TI  - Comparative phylogenetics offer new insights into the biogeographic history of
      Macaca fascicularis and the origin of the Mauritian macaques.
AB  - We employ a comparative phylogenetic analysis to gain insight into the recent
      evolutionary history of Macaca fascicularis, the long-tailed macaque.
      Mitochondrial and Y-chromosomal topologies both show that, in general, the
      deepest intraspecific bifurcations separate Indochinese and Sundaic forms of this
      species. Sumatran populations, however, are an exception: they carry one Y
      chromosomal lineage that clusters with continental populations, and another that
      clusters with insular stocks. This discovery provides insight into two events in
      the history of M. fascicularis. First, the presence of the 'continental' Y
      lineage on Sumatra is one of the strongest lines of evidence to date for recent
      (Late Pleistocene) gene flow between Indochinese and Sundaic populations. Second,
      since Sumatra is the only region known to carry 'continental' YDNA and 'insular'
      mtDNA, it is considered the most likely source of the Mauritian macaques-an
      important biomedical research stock that appears to carry this mtDNA/YDNA
      combination exclusively.

PMID- 16979913
TI  - Induction of osteoclast-like cells derived from the synovial lavage fluids of
      patients with temporomandibular joint disorders.
AB  - OBJECTIVE: Although biochemical studies have examined the synovial fluid (SF) of
      patients with temporomandibular joint (TMJ) disorders (TMDs), the details of the
      molecular mechanism of bone destruction and remodeling remain unknown. In this
      study, we induced and characterized osteoclast-like cells from the SF of patients
      with TMD and investigated the participation of these cells in the pathogenesis of
      TMD. METHODS: We collected SF cells from patients with TMD after a pumping
      procedure, cultured osteoclast-like cells, and examined their characteristics,
      including osteoclast markers and bone resorption activities. In addition, we
      obtained fibroblastic cells from the SF of TMD patients by continuous sub
      culturing. Using these fibroblastic cells, we examined fibroblast markers using
      immunocytochemical staining and analyzed the receptor activator of nuclear-factor
      kappaB ligand (RANKL) mRNA levels. Detection of soluble form of RANKL (sRANKL) in
      the SF was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS:
      Osteoclast-like cells were induced from the SF cells of patients with TMD by
      adding recombinant human (rh) macrophage colony stimulating factor (M-CSF) and
      either 1,25-dihydroxy vitamin D3 [1,25(OH)2D3] or prostaglandin E2 (PGE2). These
      multinucleated giant cells were positive for tartrate-resistant acid phosphatase
      (TRAP) and had the ability to absorb bone. The fibroblastic cells from the SF of
      TMD patients were positive for fibroblast markers and RANKL mRNA was up
      regulated. Detection of sRANKL in SF of patient group was significantly higher
      than control group. CONCLUSION: The results suggest that the joint-infiltrating
      SF cells from TMD patients play important roles in the pathogenesis of these
      disorders, which is characterized by progressive bone destruction or remodeling.

PMID- 16979911
TI  - Infrequent and unidirectional colonization of hyperdiverse Papuadytes diving
      beetles in New Caledonia and New Guinea.
AB  - We present a molecular phylogenetic analysis of 2808 aligned bp of rrnL, cox1,
      cob, H3 and 18S rRNA of all major morphological groups of Papuadytes diving
      beetles (Coleoptera: Dytiscidae) which are diverse in running water habitats
      throughout the Australian region. We focus on the origin of the fauna of the
      megadiverse islands of New Guinea and New Caledonia. Parsimony as well as
      Bayesian analyses suggest a basal position of Australian species in a
      paraphyletic series, with more recent nested radiations in New Caledonia and New
      Guinea. According to molecular clock analyses, both landmasses were colonized
      during the Miocene, which matches geological data and corroborates similar
      findings in other taxonomic groups. Our analyses suggest that dispersal played an
      important role in the formation of these large insular faunas, although
      successful colonization appears to be a rare event, and, in this case, is
      unidirectional. Whether or not a lineage is present on an island is due to
      chance: Papuadytes are absent from Fiji, where related Copelatus have radiated
      extensively in the same habitats occupied by Papuadytes in New Caledonia and New
      Guinea, while Copelatus are absent from New Caledonia. Lineages of Papuadytes
      apparently colonized New Caledonia twice, around 14 and 9 MYA according to the
      molecular calibration, and both lineages are derived from an Australian ancestor.
      The older clade is represented only by two apparently relictual mountain species
      (one morphologically strongly adapted to highly ephemeral habitats), while the
      younger clade contains at least 18 species exhibiting a great morphological
      diversity. The 150+ species in New Guinea are monophyletic, apparently derived
      from an Australian ancestor, and constitute a morphologically rather homogenous
      group. The tree backbone remains insufficiently supported under parsimony and
      Bayesian analyses, where shorter branches suggest a rapid sequence of major
      branching events.

PMID- 16979914
TI  - Efficacy and safety of intraarticular hyaluronic acid in the treatment of hip
      osteoarthritis: a systematic review.
AB  - OBJECTIVE: This study sought to use a systematic review to ascertain the efficacy
      and safety of hyaluronic acid (HA) in the treatment of hip osteoarthritis (OA).
      DESIGN: A protocolized search was made of a number of electronic databases,
      including Medline, EMBASE, Cochrane Library and Health Technology Assessment
      (HTA) among others. Two independent reviewers applied a series of inclusion and
      exclusion criteria to the studies located in the search, and selected only those
      that included more than 20 patients; had a follow-up period of more than 1 week;
      and exclusively assessed the efficacy and/or effectiveness of HA in patients with
      confirmed hip OA. RESULTS: A total of eight studies, comprising clinical trials
      and one review, met the inclusion criteria, and had study populations ranging
      from 22 to 104 patients. Only two of the trials were controlled: one compared two
      HAs of different molecular weights; and the other compared HA with corticoids and
      a placebo. Relief of pain was estimated to be around 40-50% by most studies,
      though the duration of this post-treatment effect was not known. CONCLUSIONS:
      Based on available evidence, HA treatment should only be used under careful
      supervision by the clinician and just in those cases where other treatments have
      failed in hip OA. There are methodologic limitations displayed in the literature,
      which were mainly the absence of a control group in most of the studies, overly
      short follow-up periods, and different ways of measuring outcomes.

PMID- 16979916
TI  - Beneficial effects of docosahexaenoic acid on active avoidance performance in 1K
      1C hypertensive rats.
AB  - The present study evaluated the role of chronic docosahexaenoic acid (DHA)
      supplementation on active avoidance learning task performance in experimental
      hypertension. Male Wistar rats were randomly divided into five experimental
      groups as follows: control, sham, DHA treated, 1K-1C hypertensive, and 1K-1C
      hypertensive+DHA treated. Hypertension was induced in 1K-1C rats via placing a
      silver clip (0.20-mm ID) around the left renal artery following a right
      uninephrectomy. DHA (36 mg/kg/day) was given to the treatment groups for 60 days
      by gastric gavage. Arterial blood pressure was measured by using the tail-cuff
      method. Active avoidance responses were determined by an automated shuttle-box.
      In brain (cerebrum) and hippocampus tissues, thiobarbituric acid reactive
      substances (TBARS) and nitrite levels were measured by fluorometric methods. DHA
      supplementation decreased blood pressure in hypertensive rats. Data from active
      avoidance training indicated that performance of active avoidance learning tasks
      were significantly impaired in 1K-1C hypertensive rats, but was completely
      restored by DHA supplementation. Increased cerebrum TBARS levels in 1K-1C rats
      were abolished by DHA administration. Cerebrum nitrite levels were lower in the
      DHA, 1K-1C and 1K-1C+DHA treated groups compared to controls. Hippocampus nitrite
      levels were lower in DHA treated and 1K-1C hypertensive rats compared to controls
      and higher in 1K-1C+DHA treated rats compared to the 1K-1C group. Our data
      indicates that DHA supplementation improves the performance of active avoidance
      learning tasks which is impaired in experimental hypertension. These affirmative
      changes might be due to a DHA-induced decrease in lipid peroxidation which may in
      turn limit the consumption of nitric oxide (NO) which promotes active avoidance
      learning.

PMID- 16979915
TI  - Hippocampal Mek/Erk signaling mediates extinction of contextual freezing
      behavior.
AB  - Fear memories elicit multiple behavioral responses, encompassing avoidance, or
      behavioral inhibition in response to threatening contexts. Context-specific
      freezing, reflecting fear-induced behavioral inhibition, has been proposed as one
      of the main risks factors for the development of anxiety disorders. We attempted
      to define the key hippocampal mediators of extinction in a mouse model of context
      dependent freezing. Nine-week-old male C57BL/6J mice were trained and tested for
      contextual fear conditioning and extinction. Freezing behavior scored by unbiased
      sampling, was used as an index of fear. Proteomic, immunoblot, and
      immunohistochemical approaches were employed to identify, verify, and analyze the
      alterations of the hippocampal extracellular signal-regulated kinases 1 and 2
      (Erk-1/2). Targeted pharmacological inhibition of the Erk-1/2 activating kinase,
      the mitogen activated and extracellular signal-regulated kinase (Mek), served to
      establish the role of Mek/Erk signaling in extinction. When compared to
      acquisition, extinction of contextual freezing triggered a rapid activation of
      Erk-1/2 showing a distinctive time-course, nuclear localization, and subcellular
      isoform distribution. These differences suggested that the upstream regulation
      and downstream effects of this pathway might be specific for each process.
      Dorsohippocampal injections of the Mek inhibitors U0126 (0.5 microg/site) and
      PD98059 (1.5 microg/site) immediately after the nonreinforced trials prevented
      Erk-1/2 activation and significantly impaired extinction. This effect was
      dissociable from potential actions on memory retrieval or reconsolidation. On the
      basis of these findings, we propose that hippocampal Mek/Erk signaling might
      serve as one of the key mediators of contextual fear extinction.

PMID- 16979917
TI  - Quantification and characterization of carotid calcium with multi-detector CT
      angiography.
AB  - OBJECTIVE: The aim of this study was to assess the accuracy of CT-angiography for
      identification and measurement of calcification of carotid atherosclerotic
      plaques and to characterise the content and distribution pattern of mineral
      calcium (hydroxyapatite, Ca) in carotid bifurcations and investigate its
      relationship with neurological symptoms. METHODS: Twenty-six patients with ICA
      stenosis > 60% (13 symptomatic, 13 asymptomatic) were selected for study. Ca was
      estimated from the weight of the ashed remnants of carotid endarterectomy (CEA)
      specimens in 11 patients. Calcium content (calcification volume (mm3),CV), and
      average calcium density (Hounsfield units (HU),CD), were determined by CT
      angiography. The distribution pattern of calcium within the lesion (base
      (posterior), shoulder or luminal surface) was assessed in all cases. RESULTS: CT
      derived estimation of CV and Ca mass (modified Agatston Score, (mAS) = CV x CD)
      showed a good correlation with its direct measurement in CEA specimens (r = 0.911
      and 0.993 respectively, p < 0,005). Asymptomatic patients with ICA stenosis > 60%
      showed statistically significant higher content of Ca than those who were
      symptomatic (mAS: 122.6 +/- 138.0 HU mm3 vs 42.8 +/- 59.1 HU mm3, p = 0.04).
      Calcification on the surface of the plaque was observed more commonly in
      asymptomatic patients (9/12 vs 3/15, p = 0.006). Non-calcified or plaques with
      posterior calcification were 12 times more likely to be symptomatic (OR: 12,
      95%CI 1.5-91.1, p = 0.021). CONCLUSIONS: CT-angiography permits the reliable
      quantification of calcification of carotid plaques. A lower content of calcium in
      carotid plaques, as well as its distribution in the base of the lesion, was
      associated with a greater prevalence of neurological symptoms. These parameters
      may be useful to identify those patients at higher risk of stroke.

PMID- 16979918
TI  - Dimethylarginine dimethylaminohydrolase-2 overexpression improves impaired nitric
      oxide synthesis of endothelial cells induced by glycated protein.
AB  - Nitric oxide (NO) synthesis is modulated by dimethylarginine
      dimethylaminohydrolase (DDAH) via metabolizing asymmetric dimethylarginine
      (ADMA), an endogenous NO synthase (NOS) inhibitor. This study investigated
      whether glycosylated bovine serum albumin (GBSA) could impair NO synthesis by
      inhibition of DDAH expression and activity, and whether DDAH2 overexpression
      could reverse the impaired NO synthesis induced by GBSA in endothelial cells.
      Overexpression of DDAH2 gene was established by liposome-mediated gene
      transfection in ECV304 endothelial cell line. Cells were incubated with 1.70
      mmol/L GBSA for 48h. And the expressions of DDAH1 and DDAH2, gene activities of
      DDAH and NOS in cells, as well as concentrations of ADMA and NO in media were
      assayed. The activity of DDAH and expression of DDAH2 gene but not DDAH1 gene
      were inhibited in endothelial cells after exposure to GBSA, whereas the
      concentrations of ADMA were increased concomitantly with the decrease of NOS
      activity in cells and NO production in media. Overexpression of DDAH2 gene could
      prevent the inhibition of DDAH activity induced by GBSA (0.55+/-0.02 vs 0.42+/
      0.02U/g pro; n=3; P<0.05), decrease ADMA concentration (0.59+/-0.04 vs 1.13+/
      0.11 micromol/L; n=3; P<0.01), and increase NOS activity and NO production
      (53.77+/-3.40 vs 34.59+/-2.57 micromol/L; P<0.05) compared with untransfected
      cells treated with GBSA. These results suggest that decreased DDAH activity and
      subsequent elevated endogenous ADMA are implicated in the inhibition of NO
      synthesis induced by GBSA, and overexpression of DDAH2 gene can prevent these
      changes in DDAH/ADMA/NOS/NO pathway of endothelial cells exposed to GBSA.

PMID- 16979920
TI  - Dynamics of paramagnetic agents by off-resonance rotating frame technique.
AB  - Off-resonance rotating frame technique offers a novel tool to explore the
      dynamics of paramagnetic agents at high magnetic fields (B0 > 3T). Based on the
      effect of paramagnetic relaxation enhancement in the off-resonance rotating
      frame, a new method is described here for determining the dynamics of
      paramagnetic ion chelates from the residual z-magnetizations of water protons. In
      this method, the dynamics of the chelates are identified by the difference
      magnetization profiles, which are the subtraction of the residual z-magnetization
      as a function of frequency offset obtained at two sets of RF amplitude omega(1)
      and pulse duration tau. The choices of omega(1) and tau are guided by a 2-D
      magnetization map that is created numerically by plotting the residual z
      magnetization as a function of effective field angle theta and off-resonance
      pulse duration tau. From the region of magnetization map that is the most
      sensitive to the alteration of the paramagnetic relaxation enhancement efficiency
      R(1rho)/R1, the ratio of the off-resonance rotating frame relaxation rate
      constant R(1rho) verse the laboratory frame relaxation rate constant R(1), three
      types of difference magnetization profiles can be generated. The magnetization
      map and the difference magnetization profiles are correlated with the rotational
      correlation time tauR of Gd-DTPA through numerical simulations, and further
      validated by the experimental data for a series of macromolecule conjugated Gd
      DTPA in aqueous solutions. Effects of hydration water number q, diffusion
      coefficient D, magnetic field strength B0 and multiple rotational correlation
      times are explored with the simulations of the magnetization map. This method not
      only provides a simple and reliable approach to determine the dynamics of
      paramagnetic labeling of molecular/cellular events at high magnetic fields, but
      also a new strategy for spectral editing in NMR/MRI based on the dynamics of
      paramagnetic labeling in vivo.

PMID- 16979919
TI  - Dinitrosyl-iron complexes with thiol-containing ligands: spatial and electronic
      structures.
AB  - Parameters of the EPR signals of monomeric dinitrosyl-iron complexes with 1H
      1,2,4-triazole-3-thiol (DNIC-MT), obtained by treating MT+ferrous iron in DMSO
      solution with gaseous NO, have been compared with those of the crystalline
      monomeric DNIC-MT with tetrahedral structure. Dissolved DNIC-MT were
      characterized by the isotropic EPR signal centered at g=2.03 with half-width of
      0.7 mT and quintet hyperfine structure when recorded at ambient temperature or
      the anisotropic EPR signal with g( perpendicular)=2.045, g( parallel)=2.014 from
      frozen solution at 77 kappa, Cyrillic. DNIC-MT in crystalline state showed the
      structure-less symmetrical singlet EPR signal centered at g=2.03 and half-width
      of 1.7 mT at both room and liquid nitrogen temperature. The Lorentz shape of this
      signal indicates the strong exchange interaction between these complexes in the
      DNIC-MT crystal. Being dissolved in DMSO the crystalline sample of DNIC-MT
      demonstrated the EPR signal typical for DNIC-MT, obtained by treating MT+ferrous
      iron in DMSO solution with gaseous NO. Low spin (S=1/2) d(9) electron
      configuration of DNIC-MT with tetrahedral structure (formula [(MT-S(.))(2)Fe(
      1)(NO(+))(2)](+)) was suggested to be responsible for the signal of DNIC-MT in
      crystalline state. Dissolving of the crystals of DNIC-MT may result in the change
      of their spatial and electronic structure, namely, tetrahedral structure of the
      complexes characterized by low spin d(9) electronic configuration transforms into
      a plane-square structure with d(7) electronic configuration and low spin S=1/2
      state (formula [(MT- S(-))(2)Fe(+)(NO(+))(2)](+)). The latter was suggested to be
      characteristic of other DNICs with various thiol-containing ligands in the
      solutions. The proposed mechanism of these DNICs formation from ferrous iron,
      thiol and NO shows that the process could be accompanied by the ionization of NO
      molecules to NO(+) and NO(-) ions in the complexes. Detailed analysis of the
      shape of the EPR signals of these complexes provided additional information about
      the exchange interaction typical for DNIC-MT in crystals.

PMID- 16979921
TI  - Injection of prostaglandin F2alpha into the bronchial artery in sheep increases
      the pulmonary vascular permeability to protein.
AB  - Lung injury and oedema following smoke inhalation are associated with eicosanoid
      release and the injury is heavily influenced by the tracheobronchial circulation.
      We hypothesized that injection of a vasoactive eicosanoid, prostaglandin F2alpha
      (PGF2alpha), into the tracheobronchial circulation would induce a permeability
      leak in that circulation as measured in lung lymph flow and protein content.
      PGF2alpha when injected into the bronchial artery increased lung lymph flow,
      protein content and lymph protein flux (protein times flow). The increase in
      lymph to plasma protein concentration after injection of PGF2alpha is consistent
      with an increase in vascular protein permeability since an increase in pressure
      alone would cause an increase in fluid flow in excess of protein with a fall in
      protein concentration. Ligation of the bronchial artery 3min after injection of
      the PGF2alpha largely prevented the late changes suggesting that the protein leak
      into the lymph was from the bronchial arteries.

PMID- 16979922
TI  - Effect of neonatal administration of a retroviral vector expressing alpha-L
      iduronidase upon lysosomal storage in brain and other organs in
      mucopolysaccharidosis I mice.
AB  - Mucopolysaccharidosis I (MPS I) due to deficient alpha-L-iduronidase (IDUA)
      activity results in accumulation of glycosaminoglycans in many cells. Gene
      therapy could program cells to secrete IDUA modified with mannose 6-phosphate
      (M6P), and enzyme could be taken up by other cells via the M6P receptor. We
      previously reported that newborn MPS I mice that were injected intravenously with
      10(9) (high-dose) or 10(8) (low-dose) transducing units/kg of a retroviral vector
      (RV) expressing canine IDUA achieved stable levels of IDUA activity in serum and
      had reduced disease in heart, eye, ear, and bone in a dose-dependent fashion.
      However, the dose required for improvement in manifestations of disease in other
      organs was not reported. High-dose and low-dose RV mice with an average serum
      IDUA activity of 1037+/-90 U/ml (471-fold normal) and 43+/-12 U/ml (20-fold
      normal), respectively, had complete correction of biochemical and pathological
      evidence of disease in the liver, spleen, kidney, and small intestines. Although
      mice that received high-dose RV had complete correction of lysosomal storage in
      thymus, ovary, lung, and testis, correction in these organs was only partial for
      those that received low-dose RV. Storage in brain was almost completely corrected
      with high-dose RV, but was not improved with low-dose RV. The correction of
      disease in brain may be due to diffusion of enzyme from blood. We conclude that
      high-dose RV prevents biochemical and pathological manifestations of disease in
      all organs in MPS I mice including brain.

PMID- 16979925
TI  - Nuclear factor-kappaB (NF-kappaB) and cyclooxygenase-2 (COX-2) expression in the
      oral mucosa following cancer chemotherapy.
AB  - Oral mucositis is a serious and debilitating side effect of cancer treatment.
      Greater understanding of the pathobiology of mucositis has recently led to the
      advent of targeted treatments for specific patient populations; however the
      treatment for mucositis remains palliative for most patients. Nuclear factor
      kappaB (NF-kappaB) and cyclooxygenase 2 (COX-2) are thought to play important
      roles in the development of mucositis. In this study, 20 patients undergoing
      cytotoxic chemotherapy had oral mucosal biopsies taken prior to and following
      administration of cytotoxic chemotherapy. The samples were stained for NF-kappaB
      and COX-2 using routine immunohistochemistry. The results from this preliminary
      study demonstrated statistically significant increased oral mucosal staining for
      NF-kappaB and COX-2 following cytotoxic chemotherapy and provide further support
      for the role of NF-kappaB and COX-2 in the pathogenesis of mucositis.

PMID- 16979924
TI  - Gene expression signatures that can discriminate oral leukoplakia subtypes and
      squamous cell carcinoma.
AB  - The purpose of this study is to generate a classifier for oral squamous cell
      carcinoma (OSCC) and leukoplakias (LPs), and evaluate its diagnostic potential.
      In order to identify marker gene candidates, differential gene expression between
      LPs and OSCCs were examined by cDNA microarray. The expression of 118 marker gene
      candidates was further evaluated by quantitative reverse transcription-PCR (QRT
      PCR) analyses of 27 OSCC and 19 LP tissues. We identified 12 up-regulated and 15
      down-regulated marker genes in OSCCs compared to LPs. Using Fisher's linear
      discriminant analysis (LDA), we demonstrated that 11-gene predictors among this
      novel marker set could best distinguish OSCCs from LPs (>97% accuracy), whereas a
      further seven of these gene predictors could be utilized to distinguish higher
      grade (higher than moderate) from lower grade (lower than mild) dysplasias (>95%
      accuracy). These predictor gene sets provide multigene classifiers for the
      diagnosis of pre-cancerous to cancerous transition of oral malignancy.

PMID- 16979926
TI  - Exercise therapy for trismus in head and neck cancer.
AB  - The aim of this study was to analyze retrospectively effects of exercise therapy
      on trismus related to head and neck cancer or as a consequence of its treatment,
      and to compare these effects with trismus not related to head and neck cancer.
      Medical records of patients referred to the department of physical therapy with
      the diagnosis trismus were retrieved and analyzed. Data of 27 patients with
      trismus related to head and neck cancer and data of eight patients with trismus
      not related to cancer were found. The number and type of exercises were
      registered from the records, as was the extent of mouth opening before and after
      exercise therapy. The median (IQR) number of exercise treatments was 4 (3-9.3).
      Exercises included active range of motion exercises, hold relax techniques,
      manual stretching and joint distraction. The increase in mouth opening was
      significantly (p<or= 0.05) less in the group of patients with trismus related to
      head and neck cancer (mean increase: 5.5, sd: 6.0) as compared to the increase in
      mouth opening in the group with trismus not related to cancer (mean increase:
      17.1, sd: 9.0). The mean number of treatments given to the group with trismus
      related to head and neck cancer (7.7) and the group with trismus not related to
      head and neck cancer (6.1) did not differ significantly. It is concluded that
      trismus related to head and neck cancer is difficult to treat with exercise
      therapy.

PMID- 16979927
TI  - Cyclooxygenase-2 expression in advanced nasopharyngeal carcinoma--a prognostic
      evaluation and correlation with hypoxia inducible factor 1alpha and vascular
      endothelial growth factor.
AB  - Cycloxygenase-2 (COX-2), hypoxia inducible factor 1-alpha (HIF-1alpha) and
      vascular endothelial growth factor (VEGF) can be induced by the Epstein-Barr
      virus oncoprotein latent membrane protein-1 (LMP-1) in nasopharyngeal cancer
      (NPC) cell lines. This study examined the prognostic relevance of COX-2 and its
      relationship with HIF-1alpha and VEGF expression in NPC biopsies. Primary tumor
      biopsies were obtained from 78 participants of a randomized trial who received
      radiotherapy (RT) with or without concurrent chemotherapy for locoregionally
      advanced NPC. These were analyzed for COX-2 expression and then correlated with
      age, sex, disease stage, treatment arm, survival and disease recurrence, VEGF and
      HIF-1alpha expression in a regression model. 83% of tumors expressed COX-2, 47%
      co-expressed COX-2 and VEGF, 38% co-expressed COX-2 and HIF-1alpha. On univariate
      analysis, COX-2 expression did not correlate with survival and recurrence, but
      moderate to high COX-2 expression was associated with advanced nodal stage
      (p=0.03). Although univariate analysis showed that COX-2-HIF-1alpha co-expression
      was associated with worse progression-free survival (p=0.046), time to local
      (p=0.004) and regional recurrence (p=0.007), multivariate analysis failed to
      confirm any correlation between COX-2-HIF-1alpha or COX-2-VEGF co-expression and
      survival or disease recurrence. Contrary to previous report, this study failed to
      demonstrate any prognostic significance of COX-2 expression alone or co
      expression with HIF-1alpha or VEGF in advanced NPC.

PMID- 16979928
TI  - Cervical sensory preservation during neck dissection.
AB  - Although the practice of neck dissection has greatly advanced from radical to
      function-preserving surgery, the impact of the sensory nerve-preserving neck
      surgery on the pain and quality of life (QOL) of patients has received little
      study. We evaluated neck morbidity and its impact on QOL associated with
      selective or modified radical neck dissection with or without preservation of
      cervical root branches. We conducted a retrospective cohort study comparing 24
      patients who had their cervical root branches preserved to 29 patients whose root
      branches were removed during neck dissection. The spinal accessory nerve was
      preserved and sex, age, pathologic status, side and extent of neck dissection,
      and radiotherapy were comparable between groups. The groups were compared based
      on sensory and motor functions of the neck and shoulder and questionnaires on
      depression and QOL at follow-up of mean 18.7 (range 12-34) months after surgery.
      The nerve-preserved patients showed a low incidence and severity of neck and
      shoulder pain compared to the nerve-removed subjects (p<.05). Loss of sensation
      was more frequently experienced in the nerve-removed group on the earlobe and the
      lateral neck of the operated side (p<.05). Depression and QOL scores were higher
      in the nerve-removed group and significantly correlated with pain intensity.
      Preservation of the cervical root branches reduces postoperative pain as well as
      permanent anesthetic areas of the neck. This may also improve the mental state
      and QOL of patients undergoing neck dissection.

PMID- 16979929
TI  - Complications encountered in a prospective series of 182 patients treated
      surgically for mouth cancer.
AB  - Outcomes of surgical treatment for patients with mouth cancer can be limited by
      the risk of perioperative complications. This study identifies factors that
      predict for complications in such patients. Between 1992 and 2000, 182 patients
      had surgery for mouth cancer. The patient, their medical and surgical
      characteristics as well as perioperative complications were identified.
      Univariate analysis was carried out to determine which characteristics were
      associated with complications. Complications occurred in 85 patients (47%). Fifty
      three percent of the complications were of intermediate severity and 15.6% were
      major. The operative death rate was 3.2%. Factors predicting complications
      included pre-existing cardiovascular (p<0.01) and respiratory disease (p=0.02),
      alcohol consumption (p<0.01), stage of disease, nature and scale of surgery,
      duration of surgery (p<0.01). Tracheostomies (p<0.01, OR 3.05), poor
      differentiation of tumour (p<0.05) and presence of extracapsular spread were
      predictive of complications. Patients with more complications are at increase
      risk of operative death or dying with head and neck cancer (p=0.04).
      Complications were also analysed into those that may be related to surgical
      technique and medical management. 113 (37%) complications were in this category.
      Factors influencing complications are multifactorial. Identification of risk
      factors allows individualised approach should improve outcome of treatment.

PMID- 16979930
TI  - Is there an epidemiological link between human papillomavirus DNA and basaloid
      squamous cell carcinoma of the pharynx?
AB  - The epidemiological link between human papillomavirus (HPV) DNA and basaloid
      squamous cell carcinoma (BSCC) of the pharynx was studied. The expression of p53
      protein was evaluated by immunohistochemical analysis. The presence of HPV DNA
      was evaluated by polymerase chain reaction amplification and "in situ"
      hybridization. The tobacco and alcohol consumption and the clinical outcomes of
      nine patients with BSCC of the pharynx are compared with site and stage matched
      109 conventional squamous cell carcinoma (SCC) patients. The BSCC specimens were
      analyzed for the presence of HPV DNA and p53 expression. We did not find any
      significant differences in tobacco and alcohol consumption between patients with
      BSCC and patients with SCC. No HPV DNA was detected in BSCC, and p53
      overexpression was found in five (55%) of the cases. Our results do not support
      an etiological link between HPV DNA and BSCC.

PMID- 16979931
TI  - Complexity beneath the silence.
AB  - Polycomb group (PcG)-mediated silencing by proteins that are conserved across
      plants and animals is a key feature of eukaryotic gene regulation. Investigation
      of PcG-mediated gene silencing has revealed a surprising degree of complexity in
      the molecular mechanisms that recruit the protein complexes, repress expression,
      and maintain the epigenetic silent state of target genes. This review summarizes
      our current understanding of the mechanism of PcG-mediated gene silencing in
      animals and higher plants.

PMID- 16979932
TI  - Let there be light in the nucleus!
AB  - Ambient light conditions trigger both developmental transitions, such as the
      induction of flowering, and a suite of adaptive responses, exemplified by the
      shade-avoidance syndrome. These responses are initiated by three families of
      photoreceptors that are conserved in all higher plants: the phototropins,
      cryptochromes and phytochromes (phyA--phyE, cry1--cry3, phot1 and phot2 in
      Arabidopsis). Molecular genetic studies performed mainly in Arabidopsis indicate
      that photon capture by these light sensors usually initiates rapid changes in the
      gene expression profile, leading to plant adaptation to their environment.
      Interestingly, numerous transcription factors are early targets of light
      regulation, both at the transcriptional and post-transcriptional levels.

PMID- 16979933
TI  - Genetic diversity of glucose phosphate isomerase from Entamoeba histolytica.
AB  - To investigate the molecular basis of zymodeme analysis in the enteric protozoan
      parasite Entamoeba histolytica, genes encoding glucose phosphate isomerase (GPI)
      were isolated from four representative E. histolytica strains belonging to
      zymodeme II, IIalpha-, XIV, or XIX. Two alleles were obtained from each strain;
      six alleles with eight polymorphic nucleotide positions were identified among the
      four strains. Two of these eight polymorphic nucleotides resulted in non
      conserved amino acid substitutions. Three GPI isoenzymes with distinct predicted
      isoelectric points were identified, which agrees well with the observed
      electrophoretic patterns of GPI from these strains. Amino acid comparisons of GPI
      from E. histolytica and other organisms revealed that all amino acid residues
      implicated for substrate binding and catalysis were conserved. Biochemical
      characterization of recombinant E. histolytica GPI confirmed that it possessed
      kinetic parameters similar to GPI from other organisms. The electrophoretic
      mobility of three GPI isoenzymes was examined by starch gel electrophoresis.
      Thus, we have established the molecular basis of the classical isoenzymes
      patterns that have been used for grouping E. histolytica isolates and for
      differentiation of E. histolytica from non-pathogenic Entamoeba dispar.

PMID- 16979934
TI  - Spectroscopic properties and thermal stability of Er3+ -doped TeO2-B2O3-Nb2O5-ZnO
      glass for potential WDM amplifier.
AB  - A series of novel 70TeO2-(15-x)B2O3-xNb2O5-15ZnO-1wt.% Er2O3 (TBN x=0, 3, 6, 9,
      12 and 15 mol%) tellurite glasses were prepared. The thermal stability,
      absorption spectra, emission spectra, and the lifetime of the (4)I(13/2) level of
      Er(3+) ions were measured and investigated. Three Judd-Ofelt intensity parameters
      Omega(t) (t=2, 4 and 6) (Omega(2)=(5.42-6.76)x10(-20)cm(2); Omega(4)=(1.37
      1.73)x10(-20)cm(2); Omega(6)=(0.70-0.94)x10(-20)cm(2)) of Er(3+) ions were
      calculated by Judd-Ofelt theory. It is found that the Omega(6) first increases
      with the increase of Nb2O5 content from 0 to 6 mol% and then decreases, which is
      mainly affected by the number of non-bridging oxygen ions of the glass network.
      The high peak of stimulated emission cross-section (sigma(e)(peak)=(0.77
      0.91)x10(-20)cm(2)) of Er(3+): (4)I(13/2)-->(4)I(15/2) transition were obtained
      according to McCumber theory and broad full width at half maximum (FWHM=65-73 nm)
      of the (4)I(13/2)-->(4)I(15/2) transition of Er(3+) ions were measured. The
      results indicate that these new TBN glasses can be used as a candidate host
      material for potential broadband optical amplifiers.

PMID- 16979935
TI  - Comparison of experimental and ab initio HF and DFT vibrational spectra of
      benzimidazole.
AB  - In this work, we will report a combined experimental and theoretical study on
      molecular and vibrational structure of benzimidazole. The laser Raman and Fourier
      transform infrared spectra of benzimidazole were recorded in the solid phase. The
      equilibrium geometry, harmonic vibrational frequencies, infrared intensities,
      Raman scattering activities, depolarization ratios and reduced masses were
      calculated by HF and density functional B3LYP method with the 6-311G(d,p) basis
      set. The scaled theoretical wavenumbers showed very good agreement with the
      experimental values. The thermodynamic functions of the title compound were also
      performed at HF/6-31G(d,p)/6-311G(d,p) and B3LYP/6-31G(d,p)/6-311G(d,p) levels of
      theory. A detailed interpretations of the infrared and Raman spectra of
      benzimidazole is reported. The theoretical spectrograms for FT-IR spectra of the
      title molecule have been constructed.

PMID- 16979936
TI  - Theoretical study on physicochemical properties of curcumin.
AB  - Curcumin is a yellow-orange pigment, which has attracted considerable attention
      due to its wide spectrum of biological and pharmacological activities. In spite
      of much effort devoted on curcumin, there still exist some open questions
      concerning its fundamental physicochemical properties. The present study suggests
      that the DFT and TD-DFT calculations are useful to answer these questions.
      Firstly, the thermodynamic as well as spectral parameters support that curcumin
      exists predominantly in enol form in solution. Secondly, the calculated
      absorption spectra of curcumin anions provides direct evidence that the lowest
      pK(a) of curcumin corresponds to the dissociation of enolic proton, which not
      only reconciles the controversy on this topic, but also has important
      implications on the proton-transfer/dissociation-associated radical-scavenging
      mechanisms of curcumin.

PMID- 16979937
TI  - Vibrational spectra and analysis of acetohydrazide CH3-CO-NH-NH2.
AB  - The structural stability of acetohydrazide CH(3)-CO-NH-NH(2) was investigated by
      DFT-B3LYP and ab initio MP2 calculations with 6-311+G** basis set. The C-N
      rotational barrier in the molecule was calculated to be about 26 kcal/mol that
      suggested the planar sp(2) nature of the nitrogen atom of the central NH moiety.
      The N atom of the terminal NH(2) group was predicted to highly prefer the
      pyramidal sp(3) structure with an inversion barrier of about 7-8 kcal/mol. The
      molecule was predicted to have a trans-syn (N-H bond is trans with respect to CO
      bond and NH(2) moiety is syn to C-N bond) conformation as the lowest energy
      structure. The vibrational frequencies were computed at B3LYP level of theory and
      normal coordinate calculations were carried out for the trans-syn acetohydrazide.
      Complete vibrational assignments were made on the basis of normal coordinate
      analyses and experimental infrared and Raman data.

PMID- 16979938
TI  - Alternative adaptive immunity in invertebrates.
AB  - Vertebrate adaptive immunity is characterized by challenge-specific long-term
      protection. This specific memory is achieved through the vast diversity of
      somatically rearranged immunological receptors such as antibodies. Whether or not
      invertebrates are capable of a comparable phenotypic plasticity and memory has
      long been a matter of debate. A recent study on Anopheles gambiae mosquitoes now
      establishes Down syndrome cell adhesion molecule (Dscam) as a key immune
      surveillance factor with characteristics analogous to antibodies.

PMID- 16979939
TI  - Innate immune recognition of, and regulation by, DNA.
AB  - DNA in microbes or host cells is normally sequestered from the immune system, and
      therefore inert, but becomes an active immunostimulatory molecule during
      infection or tissue damage. Recent evidence suggests that Toll-like receptor
      (TLR)9, currently the only known immune sensor for DNA, recognizes more diverse
      elements in its ligand than initially thought, and must cooperate with additional
      host factors to provoke an optimal innate immune response in the physiological
      environment. Moreover, the innate immune system possesses a TLR9-independent, as
      yet-undefined intracellular recognition machinery of double-stranded DNA that
      induces type I interferons through distinct signaling pathways. TLR9-dependent
      and TLR9-independent immune recognition of DNA might play crucial roles in DNA
      associated protective immunity and in pathological autoimmunity.

PMID- 16979940
TI  - Diversification, dioecy and dimorphism in schistosomes.
AB  - In addition to causing one of the great neglected diseases of the world,
      schistosomes have unusual biological features that further command attention,
      including their habit of living in the blood of their hosts and the presence of
      separate, dimorphic sexes. Phylogenetic studies including a more complete
      sampling of pivotal and rare schistosomes and their relatives, provide an
      improved framework for interpreting schistosome biology. From such studies, it is
      inferred that schistosomes are exclusively parasites of endotherms. It is argued
      that a commitment to life in the endothermic hepatic portal system favored a
      filiform body form for egg deposition and led to the emergence of dioecy.
      Schistosome sexual dimorphism and mating systems have subsequently been
      influenced by the duration of opportunities for transmission and by the nature of
      the vascular habitats in which they live. A comparative perspective provides
      valuable insights for interpreting the biology of schistosomes, including the
      species that cause disease in humans.

PMID- 16979941
TI  - A unified hypothesis for the genesis of cerebral malaria: sequestration,
      inflammation and hemostasis leading to microcirculatory dysfunction.
AB  - A unifying hypothesis for the genesis of cerebral malaria proposes that parasite
      antigens (released by replication in blood, surface molecules on parasitized
      erythrocytes, or merozoites) activate platelets that, in turn, contribute to the
      activation of the inflammatory response and increased levels of endothelial cell
      adhesion molecules (eCAMs). Increased levels of eCAMs result in further
      parasitized-erythrocyte sequestration and marked local inflammation that might
      disrupt the brain microvasculature, which cannot be repaired by the hemostasis
      system because of its procoagulant state. Disruption of the brain
      microvasculature can result in vascular leak and/or hemorrhaging into the brain;
      similar processes can occur in other vascular beds, including the lung. The
      blockage of functional capillaries by parasitized and/or unparasitized
      erythrocytes with decreased deformability or rosettes is also a key interaction
      between hemostasis and mechanical obstruction leading to pathogenesis. The events
      resulting in the development of cerebral malaria complications are multi
      factorial, encompassing a dynamic interaction between three processes, thereby
      explaining the complexity of this deadly syndrome.

PMID- 16979942
TI  - NIH funding of gene therapy trials.

PMID- 16979943
TI  - Preferential silencing of a common dominant rhodopsin mutation does not inhibit
      retinal degeneration in a transgenic model.
AB  - Autosomal dominant retinitis pigmentosa caused by the frequent rhodopsin P23H
      mutation is characterized by progressive photoreceptor cell death eventually
      leading to blindness and for which no therapies are available. Considering the
      gain-of-function effect exerted by the P23H mutation, strategies aimed at
      silencing the expression of the mutated allele, like RNA interference, are
      desirable. We have designed small interfering RNAs (siRNA) to silence
      specifically the P23H rhodopsin allele expressed by a transgenic rat model of the
      disease. We have selected in vitro one siRNA and generated an adeno-associated
      viral (AAV) vector expressing the short hairpin RNA (shRNA) based on the selected
      siRNA. In vitro the shRNA significantly inhibits the expression of the P23H but
      not the wild-type rhodopsin allele. Subretinal administration of the AAV2/5
      vector encoding the shRNA in P23H transgenic rats results in inhibition of
      rhodopsin P23H expression that is not able to prevent or block photoreceptor
      degeneration. Since rhodopsin is the most abundant rod photoreceptor protein,
      systems resulting in more robust shRNA expression in the retina may be required
      to achieve therapeutic efficacy in vivo.

PMID- 16979944
TI  - A contextual analysis of attention to chronic pain: what the patient does with
      their pain might be more important than their awareness or vigilance alone.
AB  - It is often believed that to feel greater pain is to experience greater effects
      of that pain, and that attention and awareness represent the transmission
      mechanism in this relationship. By implication, it is assumed that if attention
      and awareness can be lessened, the effects of pain will likewise reduce. Despite
      conceptual work and data suggesting more complex processes might indeed be in
      place, these long-standing and intuitively appealing ideas remain, either
      explicitly or implicitly, in both research and clinical applications. The purpose
      of this study was to compare the role of attentional processes in chronic pain
      with a process that is more contextual, functional, and behavior-focused, namely,
      acceptance. The hypothesis tested is whether it is more important to understand
      the amount of contact an individual has with pain, in this case awareness and
      vigilance to pain, or the degree of influence on behavior brought with that
      contact, in this case acceptance. Data from 227 patients seeking treatment for
      chronic pain were examined. Results from correlation analyses showed that
      acceptance scores achieved stronger correlations than scores for the attention
      variables with measures of cognitive, emotional, social, and physical
      functioning. When acceptance of pain was taken into account in multiple
      regression analyses, scores from the attention measures accounted for little or
      no variance in measures of patient functioning. The value of various mental,
      mechanical, behavior-focused, and contextual models of attention in chronic pain
      is discussed. PERSPECTIVE: Attention, awareness, and vigilance appear immediately
      applicable for understanding chronic pain. These processes, however, might be
      incomplete in accounting for pain-related suffering and disability. Acceptance is
      proposed as a process that expands the framework of attention to include varying
      cognitive, emotional, and social influences exerted by pain on patient behavior.

PMID- 16979945
TI  - A novel peptide from the ACEI/BPP-CNP precursor in the venom of Crotalus durissus
      collilineatus.
AB  - In crotaline venoms, angiotensin-converting enzyme inhibitors [ACEIs, also known
      as bradykinin potentiating peptides (BPPs)], are products of a gene coding for an
      ACEI/BPP-C-type natriuretic peptide (CNP) precursor. In the genes from Bothrops
      jararaca and Gloydius blomhoffii, ACEI/BPP sequences are repeated. Sequencing of
      a cDNA clone from venom glands of Crotalus durissus collilineatus showed that two
      ACEIs/BPPs are located together at the N-terminus, but without repeats. An
      additional sequence for CNP was unexpectedly found at the C-terminus. Homologous
      genes for the ACEI/BPP-CNP precursor suggest that most crotaline venoms contain
      both ACEIs/BPPs and CNP. The sequence of ACEIs/BPPs is separated from the CNP
      sequence by a long spacer sequence. Previously, there was no evidence that this
      spacer actually coded any expressed peptides. Aird and Kaiser (1986, unpublished)
      previously isolated and sequenced a peptide of 11 residues (TPPAGPDVGPR) from
      Crotalus viridis viridis venom. In the present study, analysis of the cDNA clone
      from C. d. collilineatus revealed a nearly identical sequence in the ACEI/BPP-CNP
      spacer. Fractionation of the crude venom by reverse phase HPLC (C(18)), and
      analysis of the fractions by mass spectrometry (MS) indicated a component of
      1020.5 Da. Amino acid sequencing by MS/MS confirmed that C. d. collilineatus
      venom contains the peptide TPPAGPDGGPR. Its high proline content and paired
      proline residues are typical of venom hypotensive peptides, although it lacks the
      usual N-terminal pyroglutamate. It has no demonstrable hypotensive activity when
      injected intravenously in rats; however, its occurrence in the venoms of
      dissimilar species suggests that its presence is not accidental. Evidence
      suggests that these novel toxins probably activate anaphylatoxin C3a receptors.

PMID- 16979946
TI  - Cladribine therapy in refractory celiac disease with aberrant T cells.
AB  - BACKGROUND & AIMS: Refractory celiac disease (RCD) may be subdivided into RCD
      types I and II with phenotypically normal and aberrant intraepithelial T-cell
      populations, respectively. In RCD II, transition into enteropathy-associated T
      cell lymphoma (EATL) is seen frequently. We have evaluated the effect of
      cladribine (2-CDA), a purine analogue inducing T-cell depletion, on clinical,
      histopathologic, and immunologic parameters, as well as the toxicity and side
      effects in a group of RCD II patients. METHODS: Between 2000 and 2005, 17
      patients were included (8 men, 9 women). All patients had a clonal rearrangement
      of the T-cell receptor gamma gene and immunophenotyping showed an aberrant T-cell
      population lacking surface expression of CD3, CD8, and T-cell receptor alphabeta,
      in the presence of expression of surface CD103 and intracytoplasmic CD3.
      Treatment consisted of 2-CDA (0.1 mg/kg/day) intravenously for 5 days, given in 1
      3 courses every 6 months depending on the response. RESULTS: All patients
      tolerated 2-CDA without serious side effects. Six patients (35.8%) showed a
      clinical improvement (weight gain, improvement of diarrhea, and hypoalbuminemia).
      In 10 patients (58.8%) a significant histologic improvement and in 6 patients
      (35.2%) a significant decrease in aberrant T cells was seen. Seven patients
      (41.1%) developed EATL and died subsequently. One patient died of progressive
      refractory state with emaciation. CONCLUSIONS: Treatment with 2-CDA in RCD II is
      feasible, well tolerated, and can induce clinical and histologic improvement as
      well as a significant decrease of aberrant T cells in a subgroup of patients,
      albeit it does not prevent EATL development. However, the earlier reported
      potential risk of precipitating an overt lymphoma should be taken into
      consideration.

PMID- 16979947
TI  - Fibrosis as an end point for clinical trials in liver disease: a report of the
      international fibrosis group.
AB  - Deaths due to the consequences of advanced liver fibrosis and cirrhosis remain a
      significant cause of mortality worldwide. Biologically plausible pathways
      involved in hepatic fibrogenesis have also led to the identification of numerous
      preclinical and clinical compounds that have received great interest as potential
      future therapeutic agents for patients with liver fibrosis. With this in mind,
      stake holders from academia, regulatory agencies, clinicians, and the
      pharmaceutical industry met to understand and discuss the many complex issues
      involved in developing potential therapeutic agents which act primarily through
      modifying fibrosis and to discuss appropriate end points for clinical trials in
      these patient populations. In this article, we summarize those discussions and
      attempt to highlight many of the hurdles and unanswered questions as we attempt
      to move forward and develop therapies to combat liver fibrosis.

PMID- 16979948
TI  - Serum insulin levels and the prevalence of adenomatous and hyperplastic polyps in
      the proximal colon.
AB  - BACKGROUND & AIMS: Obesity and diabetes mellitus are associated with an increased
      incidence of proximal colon cancer. Colonic adenoma that has been reported to be
      associated with elevated serum insulin levels and subsets of hyperplastic polyps
      might serve as a precursor of colon cancer. In this study, we sought to determine
      segment-specific associations between serum insulin levels and the prevalence of
      adenoma and hyperplastic polyps in the proximal and distal colon. METHODS: We
      studied 343 consecutive patients who underwent colonoscopy in our hospital. All
      medical information, including fasting serum insulin, was obtained at
      colonoscopy. We performed multinomial logistic regression models by using the
      outcome categories of none (reference), proximal-only, distal-only, and both
      segment lesions for the presence of adenoma/hyperplastic polyp with serum
      insulin, age, gender, lifestyle characteristics, and the presence of other types
      of lesions as predictors. Odds ratios (ORs) and 95% confidence intervals (CIs)
      are provided for a 5-muU/mL increase in serum insulin. RESULTS: Overall, serum
      insulin levels were significantly associated with adenoma (OR, 1.5; 95% CI, 1.1
      2.0; P = .005) and borderline associated with hyperplastic polyps (OR, 1.3; 95%
      CI, 1.0-1.7; P = .075). In multinomial logistic regression models, elevated serum
      insulin levels were significantly associated with proximal-only adenoma (OR, 1.8;
      95% CI, 1.2-2.5; P = .002), both-side hyperplastic polyp (OR, 1.7; 95% CI, 1.1
      2.5; P = .015), and proximal-only hyperplastic polyp (OR, 1.5; 95% CI, 1.0-2.1; P
      = .048) and borderline associated with distal-only adenoma (OR, 1.5; 95% CI, 1.0
      2.1; P =.059) but not with distal-only hyperplastic polyp. CONCLUSIONS: Serum
      insulin levels directly correlate with the presence of adenoma and hyperplastic
      polyps in the proximal colon and might also less strongly correlate with the
      presence of distal adenoma.

PMID- 16979949
TI  - Biliary atresia with choledochal cyst: implications for classification.
AB  - BACKGROUND & AIMS: To illustrate the limitations of the embryonic and perinatal
      classification system of biliary atresia (BA), we present a child with an
      antenatal diagnosis of choledochal cyst (CC) associated with BA and review the
      published literature. METHODS: Medline and Pubmed were searched for "BA and CC,"
      "cystic biliary atresia," "BA and cysts," and "biliary cystic malformations."
      RESULTS: A 7-week-old with an antenatal diagnosis of CC was found to have BA
      associated with CC. The literature search identified 88 cases of BA with CC.
      Sixty-seven cases had type 1 BA (atresia of the common bile duct), 2 had type 2
      BA (atresia of the common hepatic duct), and 19 had type 3 BA (atresia of the
      porta hepatis). Of the 27 cases of antenatal diagnosis of BA with CC only 1 had
      associated congenital anomalies. Outcome analysis showed poor outcomes were
      significantly more common (P = .009) and occurred earlier (P = .0249) in patients
      with type 3 BA. Children with type 3 BA were 5.4 times more likely to develop
      poor outcomes compared with type 1 (hazard ratio, 5.4; 95% confidence interval,
      1.03-27.8). CONCLUSIONS: BA associated with CC forms a distinct subtype of BA,
      characterized by a preponderance of type 1 BA, a relatively good clinical outcome
      after surgery, and an absence of associated congenital anomalies. Antenatal
      diagnosis of many affected infants supports their inclusion within the embryonic
      BA group and suggests that a broader interpretation of the embryonic phenotype
      and further classification of BA based on genetic susceptibility may be required.

PMID- 16979950
TI  - Malabsorption work-up: utility of small bowel biopsy.
AB  - A wide variety of small intestinal mucosal diseases lead to malabsorption.
      Although stool studies, especially stool for excess fat, and functional tests for
      deficiency states are important clues to malabsorption, small intestinal biopsies
      are probably the most crucial part of the diagnostic process. Many mucosal
      disorders have distinctive histologic features that allow for precise diagnosis.
      However, these histologic changes might be subtle. The role of the
      gastroenterologist is to provide the pathologist with adequate clinical
      information and tissue material to ensure a complete examination pathologically.
      Celiac disease is the most common mucosal cause of chronic malabsorption in the
      western world. Celiac disease can present classically as large volume fatty
      diarrhea, but it more commonly presents with subtle clinical symptoms or iron
      deficiency anemia. Although the histologic hallmark of celiac disease is
      increased intraepithelial lymphocytosis along with villous atrophy, increased
      intraepithelial lymphocytosis alone in an appropriate clinical context might
      suggest the diagnosis of celiac disease. The aim of this review is to highlight
      the importance of close cooperation and communication between the
      gastroenterologist and the pathologist to optimize the diagnosis of mucosal
      diseases that result in malabsorption.

PMID- 16979951
TI  - Esophageal adenocarcinoma.

PMID- 16979952
TI  - The clinical relevance of compound heterozygosity for the C282Y and H63D
      substitutions in hemochromatosis.
AB  - BACKGROUND & AIMS: Two major mutations are defined within the hemochromatosis
      gene, HFE. Although the effects of the C282Y substitution have been well
      characterized, the clinical significance of the C282Y/H63D state remains unclear.
      This study assessed the phenotypic expression in C282Y/H63D subjects as compared
      with C282Y homozygotes. METHODS: Data were obtained from 91 C282Y/H63D probands,
      158 C282Y/H63D subjects identified through family screening, and 483 C282Y
      homozygotes. Subjects underwent clinical evaluation, genotyping, biochemical
      assessment, and liver biopsy examination where clinically indicated. RESULTS:
      C282Y/H63D probands had significantly less clinical and biochemical expression
      than C282Y homozygotes. Biochemical expression was higher in C282Y/H63D probands
      than in C282Y/H63D subjects identified through family screening (P < .001). Of
      the C282Y/H63D subjects with serum ferritin levels greater than 1000 mug/L, all
      had known comorbid factors that could have contributed to the increased ferritin
      level. Of the 51 C282Y/H63D subjects who underwent liver biopsy examination,
      significantly increased iron stores were present in 9 subjects and hepatic
      fibrosis was present in 13. Twelve of the 13 had evidence of hepatic steatosis,
      excess alcohol consumption, or diabetes. The mobilizable iron level was
      significantly higher in C282Y homozygous males than in compound heterozygous
      males (P < .001). Genetic screening of C282Y/H63D first-degree relatives detected
      5 C282Y homozygotes. CONCLUSIONS: C282Y/H63D subjects referred for assessment had
      a high prevalence of increased iron indices but did not develop progressive
      clinical disease without comorbid factors such as steatosis, diabetes, or excess
      alcohol consumption. When fibrosis was seen, 1 or more comorbid factors almost
      always were present. Thus, phlebotomy therapy is warranted and cascade screening
      of relatives should be performed because expressing C282Y homozygotes may be
      detected.

PMID- 16979953
TI  - Pancreatic cancer in patients with pancreatic cystic lesions: a prospective study
      in 197 patients.
AB  - BACKGROUND & AIMS: K-ras mutation is frequently detected in pancreatic juice of
      patients with pancreatic small cystic lesions, as well as those with pancreatic
      cancer. Those cystic lesions are often found by chance with modern radiologic
      imaging modalities. In this study, we prospectively examined the prognosis of
      patients with pancreatic cystic lesions, focusing on pancreatic cancer
      development. METHODS: A total of 197 patients with pancreatic cystic lesions, 80
      with intraductal papillary mucinous neoplasm (IPMN) and 117 with non-IPMN cysts,
      were followed up for 3.8 years on average. Blood tests and imaging diagnosis were
      performed twice a year. The observed incidence of pancreatic cancer was compared
      with the expected incidence calculated on the basis of age- and gender-matched
      mortality of pancreatic cancer in the general Japanese population. RESULTS:
      Pancreatic cancer developed in 7 patients during the observation period (0.95%
      per year), infiltrating ductal carcinoma in 5 and intraductal papillary mucinous
      carcinoma in 2. Three of the ductal cancer cases had pancreatic non-IPMN cyst as
      preexisting lesion. At least 2 of the carcinomas arose in regions remote from
      preexisting lesions. The observed incidence of pancreatic cancer was 22.5 times
      higher (95% confidence interval, 11.0-45.3) than expected mortality from this
      cancer among general population. CONCLUSIONS: Patients with pancreatic cystic
      lesions are at a considerably high risk for pancreatic cancer, with a
      standardized incidence rate of 22.5. Cancer might develop in regions remote from
      the preexisting cystic lesion, suggesting diffuse pathologic changes predisposing
      to malignant transformation in the entire pancreas harboring cystic lesions.

PMID- 16979954
TI  - Assessment of differentiation and progression of hepatic tumors using array-based
      comparative genomic hybridization.
AB  - BACKGROUND & AIMS: To gain more information about the molecular mechanisms
      leading to dedifferentiation of hepatocellular adenoma (HCA) and hepatocellular
      carcinoma (HCC), high-resolution array-based comparative genomic hybridization
      (array-CGH) was performed on 24 cases of HCC and 10 cases of HCA. METHODS: DNA
      chips containing 6251 individual bacterial artificial chromosome/plasmid
      artificial chromosome clones were used. They allowed for a genome-wide resolution
      of 1 Mb and an even higher resolution of up to 100 kb for chromosome regions
      recurrently involved in human tumors and for regions containing known tumor
      suppressor genes and oncogenes. RESULTS: Copy number changes on the genomic scale
      were found by array-based comparative genomic hybridization in all cases. In HCC,
      gains of chromosomal regions 1q (91.6%), and 8q (58.3%), and losses of 8p (54%)
      were found most frequently. Hierarchic cluster analysis branched all HCA from
      HCC. However, in 2 adenomas with a known history of glycogenosis type I and
      adenomatosis hepatis gains of 1q were found, too. The critically gained region
      was narrowed down to bands 1q22-23. Although no significant differences in the
      mean number of chromosomal aberrations were seen between adenomas and well
      differentiated carcinomas (2.7 vs 4.6), a significant increase accompanied the
      dedifferentiation of HCC (14.1 in HCC-G2 and 16.3 in HCC-G2/3; P < .02).
      Dedifferentiation of HCC also was correlated closely to losses of 4q and 13q (P
      <.001 and <.005, respectively). CONCLUSIONS: The increased chromosomal
      instability during dedifferentiation of HCC leads to an accumulation of
      structural chromosomal aberrations and losses and gains of defined chromosome
      regions.

PMID- 16979955
TI  - Synthesis of collagen I in collagenous sprue.
AB  - BACKGROUND & AIMS: Collagenous sprue (CS) is a rare severe malabsorption syndrome
      of unknown etiology, characterized by villus atrophy and a broad subepithelial
      collagen band. We studied the expression patterns of genes involved in
      fibrogenesis and fibrolysis and analyzed the composition of the subepithelial
      collagen band in CS compared with untreated celiac diseases (CDs). METHODS:
      Duodenal biopsies from 2 patients with CS were hybridized with (35)S-labeled RNA
      probes for procollagen alpha1(I), matrix metalloproteinases (MMPs)-1 and -3, and
      tissue inhibitor of MMP-1 (TIMP-1). Numbers of positive subepithelial and lamina
      propria cells and grain density per cell were determined microscopically.
      Immunohistochemistry for collagens I, III, IV, XIV, and tenascin was performed by
      the immunoalkaline phosphatase method. Findings were compared with earlier data
      from patients with untreated CD. RESULTS: Numbers of cells expressing procollagen
      I, MMP-1, and MMP-3 mRNA were similar, but subepithelial procollagen I
      transcripts per cell were significantly increased (42 and 38 vs 18 [13-23]; P <
      .05) in CS compared with CD, whereas cellular transcript densities for MMP-1 and
      MMP-3 mRNA were similar. In addition, the number of TIMP-1 mRNA-positive cells
      was higher in CS compared with CD (32 and 25 vs 16.5 [4-25]; P < .05). The
      subepithelial collagenous bands stained for collagen I, collagen III, and
      tenascin. CONCLUSIONS: The prominent subepithelial matrix deposition in CS is due
      to increased expression of the main fibrogenic genes (procollagen I and TIMP-1)
      by myofibroblastic cells, whereas expression of fibrolytic MMPs remains
      unaltered.

PMID- 16979956
TI  - Population-based analyses of lymph node metastases in colorectal cancer.
AB  - BACKGROUND & AIMS: The potential presence of lymph node metastases in patients
      with colorectal cancer (CRC) limits the application of minimally invasive
      techniques of resection. We used data from the National Cancer Institute's
      Surveillance, Epidemiology, and End Results registry to better understand the
      underlying risk of lymph node metastases and factors that influence this risk in
      a population-based fashion. METHODS: In a cohort of 124,180 CRC patients
      diagnosed from 1988 through 2002 treated with radical surgery without neoadjuvant
      irradiation, we assessed the proportion of patients who were lymph node positive
      and determined factors that influenced the risk of lymph node metastases
      including patient characteristics, anatomic location, and histopathologic
      factors. RESULTS: Among all patients, the proportion of lymph node metastases was
      34.5%. The overall proportion of node positivity was 8% for T1 tumors, 18.5% for
      T2 tumors, 42% for T3 tumors, and 50% for T4 tumors. Nodal metastases were noted
      in 7% of proximal T1 colon tumors, 7.5% of distal T1 colon tumors, and 10.1% of
      T1 rectal tumors. Patients with poorly differentiated tumors were much more
      likely to be node positive (52%) than patients with well-differentiated tumors
      (20%) (P<.0001). CONCLUSIONS: Even patients with superficial CRCs have a
      significant risk of nodal metastases. This risk should be considered when
      balancing the risks and benefits of minimally invasive techniques such as local
      excision or endoscopic resection for the treatment of CRC.

PMID- 16979957
TI  - Acute gastric remnant dilation after laparoscopic Roux-en-Y gastric bypass
      operation in long-standing type I diabetic patient: Case report and literature
      review.

PMID- 16979958
TI  - Acute vena cava thrombosis after placement of retrievable inferior vena cava
      filter before laparoscopic gastric bypass.

PMID- 16979959
TI  - Cloning and expression of medaka dazl during embryogenesis and gametogenesis.
AB  - The Deleted in azoospermia family consists of RNA-binding proteins Boule, Daz,
      and Daz-like (Dazl) that are expressed in the germline. Here, we report the
      cloning and expression of the medakafish (Oryzias latipes) dazl gene (odazl).
      Interestingly, although the predicted medaka Dazl protein (oDazl) contains a RRM
      motif and a DAZ repeat characteristic of its mammalian homologs, it lacks 80 aa
      at the C-terminus. By RT-PCR, RNA in situ hybridization, Western blotting and
      fluorescent immunohistochemistry using a rabbit anti-Dazl antibody (alphaDazl),
      we analyzed the expression patterns of odazl and its protein. The odazl
      transcript persists throughout embryogenesis and delineates with primordial germ
      cells. In adults, the expression of odazl RNA and its protein is restricted to
      germ cells of both the testis and ovary. We observed differential expression of
      RNA and protein at critical stages of gametogenesis. In the testis, the odazl RNA
      is low at premeiotic stages, abundant at meiotic stages, but absent in
      postmeiotic stages; whereas the oDazl protein is rich in premeiotic stages,
      reduced at meiotic stages, becomes barely detectable or absent in postmeiotic
      round spermatids or sperm, respectively. This is in sharp contrast to the human
      situation where the Dazl transcript and protein are present in mature
      spermatozoa. In the ovary, the odazl RNA and protein persist throughout oogenesis
      and also show differential expression at premeiotic, meiotic and postmeiotic
      stages. Thus, the odazl or its protein is a marker for germ cells during
      embryogenesis and at critical stages of gametogenesis in both sexes of medaka.

PMID- 16979960
TI  - Placement of a biliary metal stent to expand a choledochus stenosis after Frey's
      surgery.
AB  - A 47-year-old patient presented with jaundice. Laboratory examinations confirmed
      cholestasis. The patient had a long history of chronic pancreatitis.
      Subsequently, cholecystectomy and a duodenum-preserving resection of the
      pancreatic head (Frey's surgery) had been performed. Endoscopic retrograde
      holangiography was done. The endoscope was inserted the normal way to the
      untouched papilla vateri. After injection of contrast medium, only the side-to
      side choledocho-jejunal anastomosis but not the common bile duct could be
      visualized because the catheter spontaneously slipped into the jejunum via the
      side-to-side choledocho-jejunal anastomosis. After introducing a catheter
      percutaneously into the intrahepatic bile duct system, a long stenosis of the
      common bile duct could be visualized. It was possible to overcome the stenosis
      with a wire, but the wire also dislocated into the jejunum via the side-to-side
      choledocho-jejunal anastomosis and could not be placed through the papilla into
      the duodenum. The problem was solved in a tricky way: A wire was introduced into
      the common bile duct via the papilla and placed into the duodenum. A loop was
      brought in percutaneously and was also placed in the jejunum. With the loop, the
      wire was grabbed and taken out percutaneously. Now a biliary metal stent could be
      positioned correctly over the wire to expand the stenosis. After the procedure
      jaundice was cured quickly. The further course was uneventful with complete
      recovery.

PMID- 16979961
TI  - Respiratory symptoms in patients with inflammatory bowel disease and the impact
      of dietary salicylates.
AB  - BACKGROUND: Respiratory symptoms are over-represented in inflammatory bowel
      disease. There are similarities between the epidemiology of inflammatory bowel
      disease and that of respiratory conditions for which an adverse influence of
      salicylate has been identified. Natural salicylates exist within our diet. AIMS:
      To determine whether a lower intake of dietary salicylates is associated with
      less active inflammatory bowel disease and fewer concurrent respiratory symptoms.
      PATIENTS AND METHODS: Respiratory status, inflammatory bowel disease activity,
      quality of life, and dietary habits were established in 73 patients with Crohn's
      disease and 69 with ulcerative colitis, using a self-administered questionnaire
      and peak expiratory flow rate readings. Harvey-Bradshaw and Simple
      Birmingham/Royal Free Colitis indices, an internally validated respiratory score,
      and estimated weekly dietary salicylate intake, were calculated for each patient.
      RESULTS: There was at least one respiratory symptom in 63.4% of patients. The
      commonest underlying respiratory diagnosis was asthma. Respiratory impairment was
      similar in ulcerative colitis and Crohn's disease; 56.3% of Crohn's disease
      patients with an active respiratory diagnosis had other extra-intestinal
      manifestations. The dietary salicylate intake was independent of respiratory
      status, but inversely correlated with ulcerative colitis activity (dietary
      salicylate intake 37.0mg versus 21.4mg for low and higher Simple Birmingham/Royal
      Free Colitis index, respectively; p<0.02). A similar association was not seen in
      Crohn's disease. CONCLUSIONS: Respiratory impairment is common in inflammatory
      bowel disease. Higher intake of dietary salicylates is associated with less
      active colitis and possibly causally so.

PMID- 16979962
TI  - Histological aspects of the terminal ileum: a windows on coeliac disease too?

PMID- 16979963
TI  - The effect of a short-term delay of puberty on trabecular bone mass and structure
      in female rats: a texture-based and histomorphometric analysis.
AB  - Accrual of bone mass and strength during development is imperative in order to
      reduce the risk of fracture later in life. Although delayed pubertal onset is
      associated with an increased incidence of stress fracture, evidence supports the
      concept of "catch up" growth. It remains unclear if deficits in bone mass
      associated with delayed puberty have long-term effects on trabecular bone
      structure and strength. The purpose of this study was to use texture-based
      analysis and histomorphometry to investigate the effect of a delay in puberty on
      trabecular bone mass and structure immediately post-puberty and at maturity in
      female rats. Forty-eight female Sprague-Dawley rats (25 days) were randomly
      assigned to one of four groups; (1) short-term control (C-ST), (2) long-term
      control (C-LT), (3) short-term GnRH antagonist (G-ST) and (4) long-term GnRH
      antagonist (G-LT). Injections of either saline or gonadotropin-releasing hormone
      antagonist (GnRH-a) (100 microg/day) (Cetrotide, Serono, Inc.) were given
      intraperitoneally for 18 days (day 25-42) to both ST and LT. The ST groups were
      sacrificed after the last injection (day 43) and the LT groups at 6 months of
      age. Pubertal and gonadal development was retarded by the GnRA antagonist
      injections as indicated by a delay in vaginal opening, lower ovarian and uterine
      weights and suppressed estradiol levels in the short-term experimental animals (G
      ST). Delayed puberty caused a transient reduction in trabecular bone area as
      assessed by histomorphometry. Specifically, the significant deficit in bone area
      resulted from a decreased trabecula number and an increase in trabecular
      separation. Texture analysis, a new method to assess bone density and structural
      anisotropy, correlated well with the standard histomorphometry and measured
      significant deficits in the density measure (M(Density)) in the G-ST group that
      remained at maturity (6 months). The texture energy deficit in the G-ST group was
      primarily in the 0 degrees orientation (-13.2%), which measures the longitudinal
      trabeculae in the proximal tibia. However, the deficit in the G-LT group was in
      the 45 degrees and 135 degrees orientations. These results suggest that any
      "catch-up" growth following the cessation of the GnRH-antagonist injection
      protocol may be directed in trabeculae oriented perpendicular to 0 degrees at the
      expense of trabeculae in other orientations.

PMID- 16979964
TI  - A novel in vivo model to study endochondral bone formation; HIF-1alpha activation
      and BMP expression.
AB  - Numerous growth and transcription factors have been implicated in endochondral
      bone formation of the growth plate. Many of these factors are up-regulated during
      hypoxia and downstream of Hypoxia-Inducible Factor (HIF)-1alpha activation.
      However, the specific function of these factors, in the context of oxygenation
      and metabolic adaptation during adult periosteal endochondral bone formation, is
      largely unknown. Here, we studied HIF-1alpha and the possible roles of (HIF
      1alpha related) growth and transcription factors in a recently developed in vivo
      model for adult periosteal endochondral bone formation. At different phases of
      periosteal endochondral bone formation, mRNA levels of Transforming Growth Factor
      (TGF)-beta1, Bone Morphogenetic Proteins (BMP)-2, -4, and -7, Indian Hedgehog
      (Ihh), Parathyroid Hormone-related Protein (PTHrP), Sox9, Runx2, HIF-1alpha,
      Vascular Endothelial Growth Factor (VEGF), periostin (POSTN), and Glyceraldehyde
      3-Phophate Dehydrogenase (GAPDH) were evaluated with RT-real time-PCR. Also
      protein levels of TGF-beta1, BMP-2, -4, and -7, HIF-1alpha, and POSTN were
      examined. During the chondrogenic phase, the expression of Sox9, Ihh, and HIF
      1alpha was significantly up-regulated. TGF-beta1 mRNA levels were rather
      constant, and the mRNA levels of BMPs were significantly lower.
      Immunohistochemical detection of corresponding gene products, however, revealed
      the presence of the proteins of TGF-beta1, BMP-2, -4, and -7, HIF-1alpha, and
      POSTN within the chondrocytes during chondrogenesis. This discrepancy in gene
      expression between mRNA and protein level for TGF-beta1 and the different BMPs is
      indicative of post-transcriptional regulation of protein synthesis. HIF-1alpha
      activation and up-regulation of GAPDH support a hypoxia-induced metabolic shift
      during periosteal chondrogenesis. Our model recapitulates essential steps in
      osteochondrogenesis and provides a new experimental system to study and
      ultimately control tissue regeneration in the adult organism.

PMID- 16979965
TI  - Accuracy in osteoporosis diagnosis of a combination of mandibular cortical width
      measurement on dental panoramic radiographs and a clinical risk index (OSIRIS):
      the OSTEODENT project.
AB  - Clinical questionnaires and dental radiographic findings have both been suggested
      as methods of identifying women at risk of having osteoporosis and who might
      benefit from bone densitometry. The aim of this study was to measure the
      diagnostic accuracy of a combination of mandibular cortical width (MCW) measured
      from dental panoramic radiographs (DPRs) and the osteoporosis index of risk
      (OSIRIS) in the diagnosis of osteoporosis. 653 women (age range 45-70 years, mean
      age 54.95 years) in four European centres underwent standardised dual X-ray
      energy absorptiometry (DXA) to provide reference data on osteoporosis status.
      Each subject was interviewed to derive OSIRIS scores and underwent DPR
      examination. MCW was measured directly by five observers. Receiver Operating
      Characteristic (ROC) curve analysis was used to calculate sensitivities and
      specificities of the clinical and radiographic tests for the diagnosis of
      osteoporosis. 512 (78.4%) of the study population were classified as having
      normal BMD and 141 (21.6%) as having osteoporosis. Using ROC analysis, OSIRIS
      gave a ROC curve area (A(z)) of 0.838, with a sensitivity of 70.9% and a
      specificity of 79.5% at a diagnostic threshold of <or=+1. MCW on DPRs gave Az
      values for the five observers ranging from 0.71 to 0.78, providing sensitivities
      between 41.0% and 59.6% and specificities of between 81.8% and 90.3% at a
      diagnostic threshold of a 3 mm MCW and sensitivities between 94.2% and 99.3% and
      specificities of between 9.8% and 23.7% at a diagnostic threshold of a 4.5 mm
      MCW. Inter-observer repeatability was less than 2.15 mm for 95% of subjects.
      Combining clinical and radiographic tests had the effect of improving specificity
      at the expense of a fall in sensitivity. Diagnostic thresholds for MCW and OSIRIS
      can be chosen to provide the sensitivity and specificity combination that best
      suits locally determined needs. However, the addition of OSIRIS as a stepwise
      'follow-up' test to radiographic assessment of MCW should only be performed if
      the aim is to have a test for which the highest achievable specificity is
      desired.

PMID- 16979968
TI  - Routine screening for the functional asymmetry of potential kidney donors.
AB  - The functional capacity of each kidney of a healthy donor may change under the
      influence of genetic and environmental factors. An assumption that the donor
      kidneys show equal function is not always true. As part of the pre-nephrectomy
      evaluation of potential donors, radioisotope renal scintigraphy using technetium
      99m diethylenetriaminepentaacetic acid (99mTcDTPA) was routinely included to
      evaluate renal functional asymmetry of undetermined etiology. The functional
      ratios of each kidney using 99mTcDTPA as well as serum creatinine (Scr) and
      creatinine clearance (Ccr) in a 24-hour urine were measured and calculated from a
      hundred donors. The left kidneys showed greater function (51.67%-53.35% under 95%
      confidence interval [CI]) and the average left versus right ratio was 52.5 versus
      47.5. The average fraction of Ccr of left kidneys was 57.8 mL/min/1.73 m +/-
      10.99 compared with right kidneys at 52.6 mL/min/1.73 m +/- 11.63. Seventy-three
      healthy volunteers donated their left kidneys, and 27, their right kidney. The
      average fraction of Ccr of the donated kidneys was 55.9 mL/min/1.73 m +/- 11.78
      compared with that of the remnant kidneys (54.5 mL/min/1.73 m +/- 11.39). After
      kidney donation, the Scr of the donors increased from 0.85 mg/dL +/- 0.17 to 1.33
      mg/dL +/- 0.27. The average postnephrectomy Ccr was 68.0 mL/min/1.73 m +/- 14.29.
      Even though the Ccr after kidney donation was higher than that of the remnant
      kidney estimated before the donation, one must pay attention to possible
      functional kidney asymmetry to select the nephrectomy site.

PMID- 16979969
TI  - Fractional creatinine clearance of the donated kidney using Cockcroft-Gault
      formula as a predictor of graft function after living donor transplantation.
AB  - To prevent hyperfiltration of the renal allograft, it is important to initially
      provide adequate functioning nephrons to meet the metabolic demands of a
      recipient. During the preoperative evaluation of a potential kidney donor, it is
      necessary to estimate the renal function of donated kidney compared with the
      metabolic needs of the recipient. The functional ratio of each kidney was
      measured using technetium-99m diethylenetriaminepentaacetic acid. The serum
      creatinine (Scr, mg/dL) and estimated creatinine clearance (Ccr, mL/min/1.73
      m(2)) using the Cockcroft-Gault formula were measured and calculated in 82
      donors. We excluded recipients who had an episode of rejection, and followed all
      recipients for more than 6 months posttransplantation. The average functional
      proportion of the donated kidney was 50.5% +/- 4.7% of the total Ccr 83.4 +/-
      18.3 of donors. The Scr of recipients at 1, 3, 6, and 9 months
      posttransplantation were significantly (P < .05) correlated with the fractional
      Ccr of the donated kidney; however, Scr at 1 year was not correlated (P = .307).
      Furthermore, the Ccr of the recipient at 1, 3, and 6 months posttransplantation
      were significantly (P < .05) correlated with the fractional Ccr of the donated
      kidney; however, the Ccr at 9 months and 1 year were not correlated (P = .094 and
      .141, respectively). The Scr and Ccr of recipients within 6 months after
      transplantation may depend on the functional mass of the donated kidney, which
      should be estimated prior to kidney donation and compared with the metabolic
      demands of the potential recipient.

PMID- 16979970
TI  - Why we consistently use the left donor kidney in living related transplantation:
      initial experience of right laparoscopic donor nephrectomy and comparison with
      left nephrectomy.
AB  - OBJECTIVES: Laparoscopic donor nephrectomy has become the method of choice for
      removal of living donor kidneys. However, the majority of laparoscopic donor
      nephrectomy cases have been limited to the left side owing to technical
      difficulties and renal vessel length. This study described the technique and
      compared donor outcomes and graft function of right and left laparoscopic donor
      nephrectomy. MATERIALS AND METHODS: Among 25 patients, 6 consecutive donors
      underwent right laparoscopic donor nephrectomy from March 2002 to January 2005.
      They were compared to 19 patients with left laparoscopic donor nephrectomy. We
      compared operative times, warm ischemia times, serial creatinines, creatinine
      clearances, complications, and graft function. RESULTS: There was no significant
      difference in any metric. The operative times (303 min. vs 274 min., P > .05) and
      warm ischemia times (133 s vs 186 s, P > .05) were similar between right and left
      laparoscopic donor nephrectomy procedures. In left laparoscopic donor
      nephrectomy, 3 patients had transient brachial plexus neuropathies. No major
      complication occurred among patients undergoing right laparoscopic donor
      nephrectomy. This study demonstrated that both donor and recipient outcomes are
      similar for right and left laparoscopic donor nephrectomy. CONCLUSIONS:
      Consistent use of the left kidney has not affected clinical outcomes. With hand
      assisted laparoscopy, the right laparoscopic donor nephrectomy is safe, providing
      excellent graft function.

PMID- 16979971
TI  - Preoperative evaluation of living related kidney donor: which kidney to donate?
AB  - OBJECTIVES: As the number of cadaveric donor is far beyond the demand of the
      waiting list, living related kidney transplantation is important for the
      worldwide organ shortage. Besides, living related transplantation has advantages
      compared with cadaveric transplantation in terms of graft function and survival.
      However, the remaining kidney function of the living donor needs to be evaluated.
      METHODS: We collected 28 paired living kidney donations from March 2003 to March
      2005. All patients underwent laparoscopic donor nephrectomy. The preoperative
      kidney evaluation included renal echography, renal nuclear scan, computed
      tomography angiography (CTA), and creatinine clearance (CCr). The renal function
      of the donor kidney was expressed as (donor kidney/both kidneys)%. The percentage
      renal function from renal echography, renal nuclear scan, and CTA were correlated
      with CCr. RESULTS: The mean percentage of donor kidney function according to
      renal echo, nuclear scan, and CTA were 49.77%, 51.83%, and 50.70%, respectively.
      The correlation coefficients for renal echography, nuclear scan, and CTA to CCr
      were -0.316, -0.201, and 0.123, respectively. The correlation coefficients for
      renal echography, nuclear scan, and CTA to postoperative serum creatinine of
      donor were 0.426, 0.036, and -0.119, respectively. CONCLUSION: From the viewpoint
      of donor postoperative residual renal function, preoperative renal sonography
      offered a better predictive value than nuclear scan or CTA.

PMID- 16979972
TI  - Tuberculin testing of kidney allograft recipients and donors before
      transplantation.
AB  - Immunocompromised patients such as those with chronic renal failure requiring
      hemodialysis (HD) are at increased risk of developing tuberculosis (TB). The gold
      standard screening tool used to detect tuberculosis is the tuberculin test, which
      owes its popularity to its ease of administration and high sensitivity. This
      study was done to identify the incidence of tuberculin test positivity among
      dialysis patients before transplantation and also in volunteer living kidney
      donors. PATIENTS AND METHODS: This cross-sectional, comparative study was done on
      308 kidney allograft recipient candidates, 80 potential living unrelated and
      related donors within a few months before transplantation, and 855 control cases
      before employment. Patients were tuberculin-tested using the Mantoux technique.
      The PPD (purified protein derivative)-positive dialysis patients were compared
      with PPD-negative subjects, regarding age, gender, dialysis duration, cause of
      chronic renal failure, and nutritional state as well as PPD test results in
      potential donors. Patients were divided into <10 mm versus > or =10 mm
      induration. Statistical analysis was performed using SPSS 11.0. RESULTS: The mean
      age of the donors was 26.6 +/- 4.6 years with a male:female ratio of 87.5%:12.5%.
      The tuberculin test was positive in 11.25% of cases, all of whom were males with
      with induration >10 mm. There was no significant difference regarding the PPD
      results and age. The mean age of recipients was 40.1 +/- 14.7 years with a
      male/female ratio of 1.3:1. The tuberculin test was positive in 33.6% of
      recipient candidates. Mean duration on dialysis was 2.5 +/- 1.2 years. No
      significant correlation existed regarding the dialysis duration, cause of renal
      failure, c-reactive protein, erythrocyte sedimentation rate, and response to
      tuberculin test. There was a direct relationship between age and PPD test results
      (Pearson correlation +192). CONCLUSION: Our results showed that more dialysis
      patients were PPD positive compared with donors.

PMID- 16979973
TI  - Experience with laparoscopic splenectomy for ABO-incompatible living renal
      transplantation without plasmapheresis.
AB  - A 25-year-old male, blood type A, was admitted to our hospital for renal
      transplantation from his father of AB blood type. Before transplant, we performed
      laparoscopic splenectomy. The serum anti-B antibody titer fell from 1:8 to 1:2.
      Therefore, plasmapheresis was not performed. The total ischemic time was 80
      minutes. Five immunosuppressive agents, including tacrolimus, mycophenolate
      mofetil, prednisolone, basiliximab, and deoxyspergualine, were administered in
      the initial period. On the 47th day, value of cytomegalovirus antibody, which was
      routinely measured, became positive. Hence, we administered ganciclovir, with a
      fall in antibody. Sixty-five days after transplant, he was discharged with a
      serum creatinine of 1.0 mg/dL. We concluded that it was possible to perform ABO
      incompatible renal transplantation with no need for plasmapheresis or rituximab.

PMID- 16979974
TI  - Preservation of renal function and cardiovascular risk factors.
AB  - An update is given about some factors leading to loss of renal allograft,
      especially in relation to the use of tacrolimus and cyclosporine. We discuss both
      immunological, such as suboptimal immunosuppression, acute rejection, and
      noncompliance, as well as nonimmunological factor's such as hypertension,
      hyperlipidemia, chronic toxic effects of immunosuppressants, older donors, and
      delayed graft function.

PMID- 16979975
TI  - Dilemmas in pediatric renal transplantation.
AB  - Solid organ transplantation, which began in adults in the 1950s, was extended to
      the pediatric population in the mid 1960s. Advances in immunosuppression and in
      surgical and medical skills have led to improving results in all types of organ
      transplantation. This success has now created many dilemmas especially in
      pediatric transplantation. In a field where the demands are high and resources
      limited, the distribution and allocation of resources becomes difficult. Complex
      decisions must be made with respect to who should be transplanted, when the
      transplant should occur, and where it should be performed. Of particular concern
      is the use of powerful immunosuppressive agents that may affect renal function
      and equally compromise patient's health with the potential for infection and
      malignancy. The various side effects of immunosuppressive agents may also cause
      difficulties in management. Decisions whether to retransplant habitual
      noncompliers are difficult. Diseases such as focal sclerosis and oxalosis, which
      recur in transplants, may affect decisions in selecting suitable recipients. The
      skills, experience, and resources of various multidisciplinary teams who manage
      these patients are often stretched to the utmost in their endeavors to achieve
      successful outcomes.

PMID- 16979976
TI  - Second and third kidney transplantations.
AB  - We reviewed the results of second and third kidney transplantations at our
      center. Among 1500 patients who had undergone kidney transplantation from 1968 to
      October 2005, we discovered 77 (male 55 and female 22 of overall mean age = 48.9
      years) second transplantations and 5 (male 4, female 1; mean age = 46.8 years)
      third transplantations. The 82 kidneys were derived from living donors in 67
      patients and from cadaveric donors in 15 patients. The mean duration from the
      first to the second transplantation was 89 months, and from the second to the
      third transplantation, 32.7 months. Among the second and third transplantations
      and graft nephrectomies, we failed to observe additional surgical complications
      compared with first transplants and over 80% graft survival at 1 year.

PMID- 16979977
TI  - Expression of fractalkine, CX3CR1, and vascular endothelial growth factor in
      human chronic renal allograft rejection.
AB  - AIM: Fractalkine/CX3CR1 system may contribute to the pathogenesis of renal
      allograft chronic rejection (CR). Vascular endothelial growth factor (VEGF) is an
      endothelial mitogen, which shows increased expression in inflammation and
      vasculopathy. This study sought describe the expression and distribution of
      Fractalkine/CX3CR1 and VEGF, and their relationship to human renal allograft CR.
      METHODS: Renal tissue from 10 patients with CR was examined for
      Fractalkine/CX3CR1 and VEGF protein by immunohistochemistry for comparison with
      patients displaying hyperacute rejection (n = 10), acute rejection (n = 10), and
      normal kidneys (n = 10). All patients were selected based upon histologically
      proven diagnoses between 1992 and 2003. RESULTS: Immunohistochemistry revealed
      that Fractalkine/CX3CR1 were mostly expressed in the tubulointerstitium and
      tubular epithelial cell basolateral membrane. Some vessels showed positive
      staining for Fractalkine/CX3CR1 as well as occasionally glomerular parietal wall
      cells. Among the CR group, VEGF was mostly expressed in tubular epithelium and
      the tubulointerstitium. A proportion of glomeruli and vessels had positive
      staining for VEGF, which was up-regulated most strikingly in the interstitial
      compartment in CR. There was markedly increased expression of Fractalkine/CX3CR1
      and VEGF protein in the interstitium of the CR compared with other groups (P <
      .05). VEGF colocalized with the expression of Fractalkine/CX3CR1. CONCLUSION:
      Fractalkine/CX3CR1 and VEGF may play an important role in the development of
      interstitial fibrosis via mononuclear cell-induced cytokine production and
      myofibroblast stimulation in CR. Further studies are necessary to identify the
      role in the pathogenesis of CR.

PMID- 16979978
TI  - Outcome of pregnancy in renal allograft recipients: SIUT experience.
AB  - The course of pregnancy and its outcome was studied in renal allograft
      recipients. Between November 1985 and November 2005, a total of 1481 renal
      transplants were carried out at the Sindh Institute of Urology and
      Transplantation (SIUT); among them were 348 females, with 73 potential females
      for pregnancy. All patients received cyclosporine and prednisolone, with 82% also
      receiving azathioprine and 4 patients mycophenolate mofetil as a third
      immunosuppressant drug. We evaluated incidence of hypertension, diabetes, pre
      eclampsia, urinary tract infection (UTI), rejection during pregnancy and during 3
      months' postdelivery as well as outcomes of pregnancy. Among 73 potential
      candidates, 31 had 47 pregnancies, after an average of 31 months (8-86 months).
      Of 31 subjects, 21 subjects were hypertensive on one or two drugs prior to
      conception. A rise in blood pressure during pregnancy was noticed in 7 patients.
      Albuminuria from trace to 3+ appeared in 13 patients and glycosuria in one other.
      Blood sugar levels remained within normal range in all subjects. UTIs occurred
      during pregnancy in 7 patients. Among 47 pregnancies, 9 had abortions (7
      spontaneous, 2 therapeutic) and 6 had preterm deliveries. The others were full
      term deliveries: 12 via a lower segment caesarean section and 20 were normal
      vaginal deliveries. Average birth weight was 4.8 lbs. At an average follow-up of
      38 months the serum creatinine values ranged from 0.94 to 2.3 mg %. One patient
      developed acute irreversible graft dysfunction soon after delivery. Our study
      demonstrated that pregnancy did not reduce renal graft survival, but newborns are
      at greater risk of premature birth and low birth weight.

PMID- 16979979
TI  - Impact of adequate dialysis before transplantation on development of chronic
      renal allograft dysfunction in 3-year posttransplant period.
AB  - INTRODUCTION: Transplantation is the preferred treatment modality for many
      patients with end-stage renal diseases. Despite all the efforts, allograft
      dysfunction remains the most important cause of graft loss. Finding new factors
      that improve graft survival is mandatory. METHODS: This prospective study
      included 93 patients transplanted between April 1999 and July 2000. The duration
      of dialysis prior to transplantation was analyzed with respect to the values
      before and up to 3 years posttransplantation, including blood urea nitrogen
      (BUN), creatinine, and blood pressure (BP) using 1-month intervals and
      triglyceride, cholesterol, low-density lipoprotein and high-density lipoprotein
      at 3-month intervals. In this study, graft dysfunction was defined as serum
      creatinine >1.8 mg/dL. Hypertension was defined as BP > 140/90 on two occasions
      or treatment with antihypertensive medications. Patients in the hypertensive
      group were divided into controlled versus uncontrolled hypertensives. RESULTS:
      The mean BUN and creatinine values of the patients prior to transplantation was
      90 +/- 30 and 10.4 +/- 4, respectively. The patients had been on dialysis for an
      average of 4.7 years. Development of renal allograft dysfunction did not show any
      relationship to the duration of dialysis ptt. Patients with higher BUN and
      creatinine levels before transplantation experienced more episodes of renal
      allograft dysfunction in the 3-year posttransplant period (P < .05 for both BUN
      and creatinine). The relationship between BUN and creatinine prior to
      transplantation and risk of renal allograft dysfunction was more powerful among
      the group of uncontrolled hypertensives. CONCLUSION: Intensive dialysis prior to
      transplantation may exert positive effects on long-term graft function and
      survival.

PMID- 16979980
TI  - Assessment of glomerular filtration rate in renal transplant patients using serum
      cystatin C.
AB  - AIM: Serum cystatin C (SCysC) has been proposed as a better marker of glomerular
      filtration rate (GFR) than serum creatinine (Scr). However, few data are
      available in renal transplant patients, especially, during the early
      postoperative phase. METHODS: Thirty-nine renal transplant patients (22 men/17
      women) were recruited for determination of SCysC and Scr before operation, at 1
      week and at 4 weeks after operation. SCysC was determined by particle-enhanced
      turbidimetric immunoassay. Creatinine clearance (Ccr) was calculated using the
      Cockcroft-Gault formula. RESULTS: SCysC and Scr levels significantly decreased
      with the recovery of allograft function. SCysC showed a significant correlation
      with Scr and Ccr. The relationship between SCysC and Scr showed a positive
      correlation (r = .849 preoperation, and r = .940 postoperation). The relationship
      between SCysC and Ccr revealed a negative correlation (r = .857 preoperation, and
      r = .876 postoperation). At the Ccr level of 50 to 80 mL/min/1.73 m(2), the
      correlation between SCysC and Ccr (r = .778) was significantly better than that
      between Scr and Ccr (r = .553; P = .032). The concentration of SCysC was not
      affected by age, gender, height, body weight, hemoglobin, serum protein, glucose,
      or mycophenolate mofetil or azathioprine dosage. However, corticosteroids
      slightly increased the level of SCysC and cyclosporine (CsA) decreased it. The
      area under the curve of the receiver operating characteristic curve for SCysC and
      Scr are 0.964 and 0.915, respectively (P < .05). CONCLUSION: Although the
      concentration may be slightly influenced by prednisolone and CsA, SCysC is more
      sensitive than Scr to detect early and moderate deterioration of GFR in adult
      renal transplant recipients.

PMID- 16979981
TI  - Creatol, an oxidative product of creatinine in kidney transplant patients, as a
      useful determinant of renal function: a preliminary study.
AB  - Creatol (CTL, 5-hydroxycreatinine) is a creatinine (Cr) oxidative metabolite,
      which was originally isolated from the urine of patients with chronic renal
      failure, representing a candidate for a uremic toxin. The effectiveness of CTL as
      an indicator of oxidative stress after kidney transplantation has not been
      reported. Therefore, we examined the relation between the change in oxidative
      stress (using CTL) in renal transplant patients and their change in renal
      function (using Cr). The serum Cr and serum and urine CTL were examined in five
      renal transplant patients. Serum CTL closely correlated with serum Cr. Serum CTL
      also correlated with urine CTL, but in some cases there was a time lag. Both the
      ratio of CTL/(Cr) and serum CTL observed in patient 2 were slow to improve after
      transplantation. The process through which oxidative stress was reduced was shown
      by the index of renal damage correlated with kidney function oxidative stress
      (using serum CTL) after transplantation. Our data suggested that CTL/Cr may be a
      good indicator of graft prognosis.

PMID- 16979982
TI  - Association of HLA class I antigen matching and early graft outcome in living
      donor kidney transplantation.
AB  - INTRODUCTION: HLA antigen matching often plays an important role in organ
      transplantation. As for HLA class I antigen matching, there are differences of
      opinion regarding its influence on the outcome of renal transplantations. The aim
      of this study was to evaluate the association of HLA class I antigen matching
      with early graft outcomes in living donor kidney transplantation. PATIENTS AND
      METHODS: We evaluated graft outcomes in the first month of transplantation. Major
      events were slow graft function (serum creatinine > 250 micromol/L at the end of
      first week), delayed graft function (patients requiring dialysis in first week),
      and acute rejection episode. Graft outcomes were compared for normal renal
      function (NRF, serum creatinine < or = 175 micromol/L) impaired renal function
      (IRF, serum creatinine > 175 micromol/L) or impaired graft function due to an
      acute rejection episode (IGF). RESULTS: The 115 subjects had a mean age of 29 +/-
      8 years and their donors 38 +/- 11 years (P < .01). Immunosuppression included
      prednisolone, azathioprine, and cyclosporine. Parents, siblings, and others were
      kidney donors in 46%, 33%, and 21%, respectively. Comparisons between NRF/IRF
      (serum creatinine 133 +/- 24 vs 201 +/- 36 micromol/L, P < .01) and NGF/IGF
      (serum creatinine 146 +/- 44 vs 161 +/- 39 micromol/L, P < .05) showed no
      difference in number or pattern of HLA matching. CONCLUSION: HLA class I antigen
      matching may not produce an added influence on early graft outcome among living
      donor kidney transplantations.

PMID- 16979983
TI  - Can monitoring of serum 8-OHdG level for 2 hours after renal transplantation
      predict prognosis of the graft?
AB  - 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is an oxidant of deoxyguanosine, a base in
      the construction of DNA. We examined the extent of DNA damage to the graft
      through oxidative stress after renal transplantation. Seven renal transplant
      patients were enrolled in this study. Before reperfusion of the grafts, the level
      of serum 8-OHdG was measured using enzyme-linked immunosorbent assay. No
      relationship was found between the level of serum 8-OHdG just before reperfusion
      and the postoperative course. In all cases, the level of serum 8-OHdG increased
      after reperfusion and decreased within 2 hours. In six cases, it remained almost
      the same as the preoperative level. A faster rate of decrease from the first peak
      of serum 8-OHdG was associated with a lower nadir serum creatinine and reduced
      occurrence of acute rejection. This study suggested that immediate calming of the
      oxidative stress following reperfusion may potentially have a positive influence
      on graft prognosis. In addition, biomarkers of oxidative stress may predict graft
      prognosis.

PMID- 16979984
TI  - Significance of protocol biopsies in living related renal transplant recipients.
AB  - INTRODUCTION: Subclinical rejection (SCR) in a normally functioning renal
      allograft may have an impact on long-term graft outcome. SCR detection is best
      done by protocol biopsies in clinically normal grafts. METHODS: We evaluated 20
      stable living related renal allografts with protocol biopsies on days 7 and 90
      posttransplant. SCR when detected was treated with a 3-day pulse of
      methylprednisolone therapy. The outcomes of these grafts were compared with 63
      other clinically stable renal allografts that did not undergo protocol biopsies.
      RESULTS: SCR was observed in 60% of cases. The patients who received
      antirejection therapy for SCR based on protocol biopsies showed better graft
      survival and mean serum creatinine values at the end of the follow-up period.

PMID- 16979985
TI  - Kidney ultrasound is useful tool in posttransplant follow-up.
AB  - OBJECTIVES: Renal sonography has been an important imaging tool in surveys of
      kidney diseases. We reviewed our experience in the finding and management of
      asymptomatic patients who underwent renal transplantation. METHODS: We performed
      baseline graft and native kidney sonography after renal transplantation, as well
      as annually even if the patient was asymptomatic. At the end of 2004, a total of
      326 transplant cases had been annually surveyed. If the findings were positive,
      they were compared with previous data to determine the need for further
      examinations and management. RESULTS: The native kidneys of 105 patients were
      abnormal. Cysts were detected in 71 cases, 23 of which were bilateral. Stones
      were found in 15 cases. Polycystic kidney disease was identified in 5. The
      findings in these 91 patients were the same as before. Moderate hydronephrosis
      was observed in 14 cases. Nine had native ureteral cancer and underwent
      nephroureterectomy. Ureteral stricture was found in the other 5 patients. Forty
      five grafts were abnormal. Thirty-one showed hydronephrosis and 2 underwent
      ureteral reimplantation. Asymptomatic stones were found in 2. A new single renal
      cyst was found in 2 cases; and multiple cysts in one other. Elevated RI on color
      Doppler was discovered in 12 patients, 4 of whom lost their grafts this year.
      Serum creatinine values of 6.9 and 2.2 mg/dL were observed in 2 patients.
      CONCLUSIONS: Renal sonography screening is useful not only for the graft but also
      for the native kidney. Hydronephrosis is an important finding. The high
      possibility of urothelial malignancy should be expected, requiring further
      examination and sequential follow-up. Elevated RI is a clue to predict graft
      outcome; rapid deterioration was observed within months.

PMID- 16979986
TI  - Oxidative status in stable renal transplantation.
AB  - Increased oxidative stress and hyperhomocysteinemia are frequently observed in
      patients with end-stage renal disease. The effects of kidney transplantation on
      oxidative state are incompletely understood. With an aim to evaluate the
      prevalence and severity of oxidative stress in living donor renal transplant
      recipients, we conducted a cross-sectional study. Thirty-five renal transplant
      recipients (mean age 34 years; body mass index 21.93 +/- 1.92) with normal renal
      function (mean serum creatinine 1.41 +/- 0.33 mg%) were enrolled in the study.
      All patients were on cyclosporine-based immunosuppression. We assessed serum
      nitric oxide (NO) levels, plasma total homocysteine levels (tHCy), and
      malonaldehyde (MDA) levels. We evaluated the antioxidant power ferric reducing
      ability of plasma (FRAP) assay. The mean duration to the first sampling was 9.23
      months after transplantation. Fourteen age- and sex-matched normotensive people
      were used as controls. The mean tHCy was significantly higher among patients
      (15.29 +/- 0.66 mmol/L compared with controls (9.58 +/- 2.90 mmol/L; P < .05).
      The MDA levels in patients (6.405 +/- 2.05 nmol/mL) were comparable to controls
      (6.093 +/- 1.93 nmol/mL; P = .099). The status of antioxidative power as measured
      by FRAP showed a trend to higher antioxidative status (697.57 +/- 103.07 mmol/L)
      in patients compared with controls (518 +/- 120.99 mmol/L; P = NS). The mean NO
      levels in patients (545.01 +/- 281.49 mmol/mL) were significantly higher than
      controls (183.49 +/- 64.53 nmol/mL; P < .05). Stable renal transplant recipients
      display a pattern of increased oxidant stress that may be counterbalanced by an
      enhanced antioxidant mechanisms.

PMID- 16979987
TI  - Abdominal aortic aneurysm repair in kidney transplant recipients.
AB  - Renal transplant recipients currently survive many years with a consequent
      increase in the risk of presentation with vascular diseases. So aortic
      reconstruction in transplant patients has been increasingly reported the most
      common procedures involving abdominal aorta aneurysms (AAAs). The most important
      problem during the operation is ischemic injury to the transplanted kidney during
      aortic clamping. Protection for the grafted kidney from ischemic or reperfusion
      injury may be achieved by permanent or temporary axillo-femoral, femoro-femoral,
      aorto-iliac bypass, cold perfusion, local cold preservation, or
      autotransplantation. Some authors have reported protection of the transplanted
      kidney function without any other procedures. We had experience with four AAA
      cases in kidney transplant patients, including two cases of direct reconstruction
      of the AAA without any other surgical protection, one autotransplantation, and
      one AAA excision with using temporary aortofemoral bypass with good results.
      Herein, we report two cases of successful AAA excision without a surgical
      procedure for graft protection.

PMID- 16979988
TI  - Effect of basiliximab on renal allograft rejection within 1 year after
      transplantation.
AB  - Basiliximab is widely used in clinical practice for initial immunosuppressive
      treatment of renal transplant recipients, seeking to reduce the incidence of
      acute rejection episodes without adverse events. This retrospective study
      included 123 renal allograft recipients transplanted at a single center. All were
      followed for longer than 1 year after transplantation and treated with
      calcineurin inhibitor and steroid (methylprednisolone) for prophylactic
      immunosuppression, but basiliximab and mycophenolate mofetil were optional. We
      compared the outcomes of renal transplant recipients who were versus treated were
      not with basiliximab as initial immunosuppressive therapy. Basiliximab was used
      for initial immunosuppression in 42 patients. Their maintenance immunosuppressive
      treatment included triple (n = 44) or double (n = 79) regimens, including a
      calcineurin inhibitor (cyclosporine [n = 87] or tacrolimus [n = 36]),
      methylprednisolone with or without mycophenolate mofetil. Twenty-six (21.1%)
      patients had a rejection episode within 1 year after transplantation and 22
      (17.9%) had infections. Within the first year after transplantation the patients
      who were treated with basiliximab showed fewer rejection episodes (n = 6, 14.3%)
      than the patients without this therapy (n = 20, 24.7%), which was not
      statistically significant (P = .245). However, basiliximab significantly affected
      the occurrence of rejection episodes among the double immunosuppressive regimen
      group (P = .006), but not the triple regimen group (P = .098) without an impact
      on infection episodes (P value of double, triple = .291, .414) within 1 year
      after transplantation. We concluded that basiliximab was more useful for the
      recipients treated with double immunosuppression with a calcineurin inhibitor and
      steroid than for those on a triple regimen including mycophenolate mofetil.

PMID- 16979989
TI  - Tacrolimus (Pan Graf) as de novo therapy in renal transplant recipients in India.
AB  - The safety and efficacy of tacrolimus in transplantation is well established.
      However, tacrolimus has only recently been available in India. We report an
      initial experience using tacrolimus as de novo therapy in a living related renal
      transplant program. Fifty-two consecutive recipients of living renal allografts
      were treated with tacrolimus, mycophenolate mofetil, or azathioprine and
      steroids. The dose of tacrolimus was adjusted to keep trough levels at 10 to 12
      ng/mL in the first 3 months, 8 to 10 ng/mL in the next 3 months, and 5 to 8 ng/mL
      thereafter. Any evidence of graft dysfunction was evaluated by graft biopsy. The
      effect of this regimen on the lipid profile as well as the incidence of
      posttransplant diabetes mellitus was evaluated in an Indian population. All
      patients were followed for periods ranging from 6 to 72 weeks (mean = 29 weeks).
      The incidence of acute rejection was 3.84%; 17.3% developed posttransplant
      diabetes mellitus. Graft and patient survivals at the current follow-up were 100%
      and 96.26%. In conclusion, tacrolimus is a safe and effective immunosuppressant
      in a living related renal transplant program.

PMID- 16979990
TI  - Influence of everolimus on cyclosporine Neoral pharmacokinetics in Chinese de
      novo cardiac transplant recipients.
AB  - OBJECTIVE: This study sought to determine the influence of everolimus on
      cyclosporine Neoral (CsA) pharmacokinetics over the first 6 months after heart
      transplantation in Chinese recipients. METHODS: Six de novo cardiac recipients
      receiving a CsA-everolimus-based immunosuppressive regimen after rabbit
      antithymoglobulin sequential immuno-induction were compared with six age-matched
      recipients receiving a CsA-azathioprine-based regimen. We compared CsA 12-hour
      area-under-curve (AUC) of the first dose (PK-1) and steady state dose (PK-S) at 1
      month after transplantation. The CsA trough concentrations (Cmin) were compared
      over the first 6 months after transplantation. RESULTS: There was no significant
      difference between the two groups in age, gender, and body weight. With respect
      to dose-normalized CsA AUC(0-infinity) of PK-1 and dose-normalized CsA AUC(0-12)
      of PK-S, the difference between the everolimus- and the azathioprine-based
      regimens was not significant. The dose-normalized CsA trough concentrations
      (Cmin/dose) were significantly lower in the everolimus-based group than in the
      azathioprine-based group during the first 5 months after heart transplantation,
      but the difference was not significant at posttransplantation month 6.
      CONCLUSIONS: When CsA pharmacokinetic profiles were considered, the CsA dose
      requirement was not lower in Chinese patients receiving everolimus than that in
      patients receiving azathioprine. The results differed from reports from Western
      countries.

PMID- 16979991
TI  - Comparison of transplanted kidney function in patients on two different doses of
      mycophenolate mofetil.
AB  - INTRODUCTION: Mycophenolate mofetil (MMF), an immunosuppressant that is widely
      used in renal transplant recipients, is associated with several dose-dependent
      hematologic and gastrointestinal side effects that lead to drug dose reduction or
      even discontinuation. The aim of this study was to compare the renal function and
      acute rejection rates of kidney allograft recipients who were on two different
      mycophenolate mofetil doses. METHODS: In a prospective study, 59 allograft kidney
      recipients who were on MMF 2 g/d were randomly selected and followed for
      evidences of acute rejection or drug side effects. Four patients were excluded
      from the study due to noncompliance, graft loss, and patient loss from
      opportunistic infection. Of the remaining 55 patients, 22 patients (40%)
      underwent MMF dose reduction to 1.35 +/- 0.23 g/d due to perceived side effects
      or economic reasons (group 1). The mean time for this change was 4.2 +/- 2.1
      months after the kidney transplantation. The remaining patients (group 2, n = 33,
      60%) had no change in MMF 2 g/d drug dosage. All patients were followed for at
      least 30 months after transplantation. Renal function tests (blood urea and serum
      creatinine) were measured monthly. Statistical analysis was performed using SPSS
      11.0 (Student t test). A P value < .05 was considered significant. RESULTS: The
      two groups were comparable regarding age, gender, other immunosuppressive
      medications, and the time after transplantation. There were no episodes of acute
      rejection in group 1 after MMF dose reduction. The renal function (blood urea or
      serum creatinine levels) was comparable between the two groups at the end of
      study (P = .846 and .610, respectively). CONCLUSION: MMF dose reduction was not
      associated with an increased risk of acute renal allograft rejection or impaired
      graft function.

PMID- 16979992
TI  - Mycophenolate mofetil (Cellcept) in pediatric renal transplantation.
AB  - Mycophenolate mofetil (MMF) was introduced in pediatric renal transplantation
      almost 10 years ago. In several pediatric studies, MMF has been associated with
      improved graft survival and improved renal function with standard
      immunosuppression of steroids and calcineurin inhibitors (CNI). Both drugs are
      associated with significant negative effects including influence on growth, blood
      pressure, glucose metabolism, and also cosmetic side effects. Reduction of CNI
      was possible with MMF without increased rejection, improving blood pressure and
      renal function. Information is accumulating that steroid-sparing protocols
      including CNI are also associated with clinical improvement. Recent reports are
      positive in the pediatric population using the combination of induction with
      interleukin-2-receptor antagonists and mTOR inhibitors to spare steroids and CNI.
      Therefore MMF remains a mainstay of immunosuppressive protocols in the pediatric
      renal transplantation.

PMID- 16979993
TI  - Comparison of enteric-coated mycophenolate sodium with mycophenolate mofetil in
      living renal allograft transplantation.
AB  - OBJECTIVE: Enteric-coated mycophenolate sodium (MPS) has been developed to
      decrease the GI side effects of mycophenolate mofetil (MMF). We did a
      retrospective analysis of 112 patients to compare the safety and efficacy of
      enteric coated MPS vs MMF in living renal transplantation. METHODS: Patients were
      divided into two groups. Group A who received MPS [Novartis, Basel, Switzerland]
      [1.08-1.44 g/d] included 53 patients of mean age 33.5 +/- 11.9 yrs, and M:F
      gender ratio 37:15 with a mean donor age of 43.2 +/- 9.9 years. Group B who
      received MMF [1.5-2.0 g/d] included 59 subjects of mean age 33.2 +/- 9.9 yrs and
      M:F gender ratio 57:6, with a mean donor age of 41.4 +/- 10.9 years. All patients
      received cyclosporine and prednisolone in addition to mycophenolate. Mean follow
      up in the two groups was 11.6 +/- 7.0 and 12.6 +/- 8.5 months, respectively.
      RESULTS: There were 11 (20.7%) rejection episodes in Group A and 12 (20.3%)
      rejection episodes in Group B (P = NS). Incidence of CMV disease was 9.61% and
      10.1%, and of other infections, 88.7% and 74.7% in Groups A and Group B,
      respectively [P = NS]. The incidence of GI (18.9% & 20.3%) and hematologic
      toxicities (9.4% & 5.1%) were similar in the groups. Patient and graft survivals
      in Group A were 91.9% & 86.6%, and in Group B was 91.3% & 91.3%, respectively [P
      = NS]. CONCLUSION: Mycophenolate sodium is an alternative immunosuppressant to
      mycophenolate mofetil in kidney transplant recipients with a similar efficacy and
      safety profile.

PMID- 16979994
TI  - Pharmacokinetics of mycophenolic acid and its glucuronide after a single and
      multiple oral dose of mycophenolate mofetil in Chinese renal transplantation
      recipients.
AB  - PURPOSES: To compare the pharmacokinetic parameters of mycophenolic acid (MPA)
      and mycophenolic acid glucuronide (MPAG) after single and multiple oral
      administration of mycophenolate mofetil (MMF) in Chinese renal transplant
      patients with those of recipients in other countries. METHODS: Twelve Chinese
      renal transplant patients after an overnight fast received a single 1-g dose of
      MMF before renal transplantation. Thereafter the patients received 1 g MMF twice
      a day up to and on the day 12 after renal transplantation. The concentrations of
      MPA and MPAG were simultaneously measured by RP-HPLC. The concentration-time data
      were examined with Drug and Statistics pharmacokinetic software. Using paired
      samples t test (self-contrast) with SPSS statistical software (alpha = 0.05), we
      compared the pharmacokinetic parameters between single and multiple doses.
      RESULTS AND DISCUSSIONS: The MPA concentration-time profiles were fitted to a two
      compartment open model; MPAG concentration-time profiles were fitted to a single
      compartment open model. Compared with the literature reports, the main
      pharmacokinetic parameters of MPA and MPAG shown by our research revealed some
      differences. The parent drug MMF was undetectable in plasma during oral
      administration. A secondary peak of MPA occurred at 6 to 10 hours, which was
      attributed to enterohepatic recirculation. There was significant variation in MPA
      and MPAG plasma concentration-time data among subjects. It is suggested that
      therapeutic drug monitoring should be applied for dosage optimization.

PMID- 16979995
TI  - Therapeutic drug monitoring of mycophenolic acid can be used as predictor of
      clinical events for kidney transplant recipients treated with mycophenolate
      mofetil.
AB  - OBJECTIVE: This study was designed to investigate the relationship between
      clinical events and the pharmacokinetics of mycophenolic acid (MPA) in adult
      renal transplant patients. METHODS: Thirty-seven adult kidney transplant
      recipients received a cyclosporine, mycophenolate mofetil, and steroids. MPA
      AUC(0-12) was obtained before and 12 days after grafting by RP-HPLC. Predose
      blood samples were measured for MPA-C(0) were gathered from all the recipients at
      4, 12, and 21 days as well as 1, 1.5, 2, 2.5, 3, and 6 months after grafting. The
      clinical events at corresponding time points were recorded to correlate with each
      MPA-C(0) value. RESULTS: In addition to single-dose and multidose MPA-AUC(0-12),
      357 MPA-C(0) values were obtained from 37 patients. The 357 units were divided
      into three subgroups: group A patients, including 239 units (66.9%), experienced
      uneventful outcomes; group B of 100 units (28.0%) showed MPA-related side
      effects, and group C, 18 units (5.0%) of acute rejection episodes. MPA-C(0) for
      groups A, B, and C were 0.8416 +/- 0.1373 mg/L, 1.5903 +/- 0.3741 mg/L and 0.6057
      +/- 0.2338 mg/L, respectively (P < .001 between groups A and B, groups B and C,
      and P = .021 between groups A and C). The three groups were also divided into an
      initial phase (< or =1 month, 251 units) and a stable phase (>1 month, 106
      units). The relationship between MPA-C(0) and associated clinical events was also
      investigated. CONCLUSION: Our results suggested a relationship between MPA
      pharmacokinetics and clinical events. The MPA-C(0) might be an appropriate
      pharmacokinetic monitoring parameter for kidney transplantation.

PMID- 16979996
TI  - Comparison of generic cyclosporine microemulsion versus neoral in de novo renal
      transplant recipients managed by 2-hour postdose monitoring.
AB  - INTRODUCTION: The bioequivalence of generic formulations is established by
      measuring pharmacokinetic parameters in healthy volunteers. Cyclosporine (CsA)
      absorption and exposure is known to differ between healthy volunteers and
      transplant recipients. Therefore bioequivalence testing may be inadequate to
      ensure therapeutic equivalence. We sought to compare the efficacy of generic
      cyclosporine (ArpimuneME, RPG Life Sciences) versus Sandimmune Neoral in de novo
      renal transplant recipients. METHODS: A prospective single-center, open-label
      study enrolled 20 de novo renal transplant patients (group 1: mean age 30.55 +/-
      9.81 years, M:F 19:1, mean donor age 43.4 +/- 10.8). All patients received
      ArpimuneME along with azathioprine and prednisolone. The results were compared
      with 17 matched controls (group 2: mean age 28.1 +/- 9.5 years, M:F 13:4, mean
      donor age 47.8 +/- 6.8) who received Neoral and were transplanted during the same
      period. C(2) levels were monitored by the cloned enzyme donor immunoassay
      (CEDIA). RESULTS: Patient and graft survivals were 100% and 100% and 100% and
      92.8% in groups 1 and 2, respectively (P = NS). Six patients (30%) experienced
      rejection in group 1 as compared eight patients (47.1%) in group 2. Mean CsA
      levels (ng/mL) during the first month were 1419.1 +/- 213.6 and 1460.5 +/- 290.7
      and at 3 months, 1296.3 +/- 227.8 and 1342.4 +/- 303.4 in the two groups,
      respectively (P = NS). The mean serum creatinine levels (mg%) in group 1 and
      group 2 were 1.6 +/- 0.8 and 2.0 +/- 1.4 at discharge and 1.5 +/- 0.4 and 1.5 +/-
      0.8 at 6 months, respectively (P = NS). CONCLUSION: Use of a generic
      microemulsion form of CsA provided safe and effective immunosuppression compared
      with Sandimmune Neoral when drug monitoring was performed by C(2) levels.

PMID- 16979997
TI  - Steroid withdrawal increases risk of acute rejection but reduces infection: a
      meta-analysis of 1681 cases in renal transplantation.
AB  - OBJECTIVE: To evaluate the safety of steroid withdrawal in renal transplantation
      recipients. METHODS: These following databases were searched: Medline (1966 to
      September 2005), OVID (1966 to 2004), Embase (1984 to 2004), Cochrane library
      (issue 4, 2005), Highwire (1849 to September 2005), American Transplant Congress
      (2005), Chinese Biomedicine database (CBM 1994 to 2005). The safety was measured
      by the following factors: patient and graft survival, acute rejection, chronic
      rejection, infection, serum creatinine. We performed meta-analysis by using
      Revman 4.2.7. RESULTS: Nine randomized clinical trials were identified to have a
      steroid withdrawal and a steroid continuing group. They included 1681 patients:
      845 with steroid withdrawal and 836 with continuing steroid. The risk of acute
      rejection after steroid withdrawal was two times higher than steroid-continuing
      group (RR 2.05; 95% confidence interval [CI]: 1.54, 2.72; P < .00001), while the
      incidence of opportunistic infection and urinary tract infection of steroid
      withdrawal group were lower than the control group (RR 0.80; 95%CI 0.64, 1.00; P
      = .05 vs RR 0.74; 95%CI, 0.60, 0.92; P = .004, respectively). The graft and
      patient survivals, chronic rejection, and serum creatinine were similar to the
      steroid continuing group. CONCLUSION: Steroid withdrawal can significantly
      increase the risk of acute rejection episodes, but reduces the incidence of
      infection to a certain extent. To prophylaxis against serious infection, steroid
      withdrawal is worth considering using a sufficient immunosuppressive regimen. The
      key point is to balance the benefit and harm for the individual recipient.

PMID- 16979998
TI  - Efficacy of isoniazid prophylaxis in renal allograft recipients.
AB  - The efficacy of isoniazid (INH) prophylaxis in renal allograft recipients who are
      on long-term immunosuppression in a region highly prevalent for tuberculosis (TB)
      was studied. INH (300 mg/d in patients weighing more than 35 kg and 5 mg/kg/d in
      patients with <35 kg body weight) together with Pyridoxine 50 mg/d for 1 year was
      started in randomly assigned renal allograft recipients. Occurrence of clinical
      tuberculosis during the initial 2 years posttransplantation was observed in the
      risk group and patients at no risk. Risks were defined as acute rejection
      episodes and exposure to antirejection therapy, past history of TB completely or
      incompletely treated, radiological evidence of past tuberculosis, history of
      tuberculosis in close contacts. Among 480 patients registered in the study, INH
      prophylaxis was given to 219 randomly assigned renal allograft recipients.
      Results were compared among patients developing TB during the initial 2 years
      posttransplantation in both the groups. Risk factors were analyzed for comparison
      in both groups. No significant difference was observed in terms of past history
      of TB, TB in close contacts, episodes of acute rejection during the initial 3
      months, and comorbidities such as cytomegalovirus infection, hepatitis C virus
      infection, and posttransplant diabetes. One patient from the INH group and 10
      patients from the non-INH group developed TB during the initial 2 years
      posttransplantation (P < .0001). None of patients required discontinuation of
      INH. INH was observed to be safe and effective as a chemoprophylactic agent in
      renal allograft recipients.

PMID- 16979999
TI  - Polyoma virus-associated nephropathy and concurrent cytomegalovirus infection in
      the kidney transplant recipients.
AB  - INTRODUCTION: Cytomegalovirus (CMV) and polyoma virus BK (BKV) may both establish
      latency following primary infection. Frequent reactivation of these viruses can
      occur in the kidney transplant recipients. BKV may induce CMV gene expression by
      stimulating cellular regulator proteins or by its own gene regulator proteins. A
      high rate of concurrent CMV infections has been noted in kidney transplant
      recipients with polyoma virus-associated nephropathy (PVAN). METHODS: PVAN was
      identified in 10 of 191 patients who received kidney transplants between October
      1998 and September 2003. PVAN was confirmed by allograft kidney biopsy. Four of
      the 10 patients were complicated by concurrent CMV infection. RESULTS: Two
      patients had only serological evidence of CMV infection and one patient had CMV
      gastritis. These three patients were treated with intravenous ganciclovir with
      good results. Disseminated ganciclovir-resistant CMV disease was demonstrated in
      the remaining patient. This 34-year-old kidney transplant recipient with PVAN
      died of multiorgan failure despite antiviral therapy with both ganciclovir and
      foscarnet. CONCLUSION: PVAN with concurrent CMV infection in kidney transplant
      recipients showed variable clinical courses including mortality. Further studies
      are needed to elucidate the influence of PVAN on the pathogenesis of CMV
      infection.

PMID- 16980000
TI  - Efficacy of high-dose trimethoprim-sulfamethoxazol prophylaxis on early urinary
      tract infection after renal transplantation.
AB  - Urinary tract infection (UTI), a major cause of morbidity in renal transplant
      recipients, has also been found to increase mortality. The first month post
      kidney transplantation is considered the critical time, with most UTI episodes
      during this period. The aim of this study was to compare the efficacy of various
      doses of trimethoprim-sulfamethoxazole (TMP/SXT) for the prophylaxis of the
      posttransplant UTI within the first month after kidney transplantation. In a
      prospective, double-blind, randomized, clinical trial, 95 kidney allograft
      recipients were divided into two groups: group 1 (n = 63) received low to
      moderate doses of TMP/SXT (either 80/400 mg or 160/800 mg, daily) and group 2 (n
      = 32), high doses of TMP/SXT (320/1600 mg, daily in two divided doses). These
      groups were comparable regarding age, gender, type of donor, and ureteral
      anastomosis and immunosuppressive therapy. UTI was defined as a urine culture
      containing more than 10(5) colonies. The mean age of the patients was 37 +/- 12.2
      years with a male/female ratio of 0.98/1. The urine culture was positive in 39
      patients (41.1%). UTI was more common among female than male patients (P = .003).
      Escherichia coli was the most common isolated organism in both groups (53.8%).
      UTI was observed in about 25% of patients on the high-dose versus 49.2% of those
      on low- to moderate-dose prophylaxis (P < .05). In conclusion, prophylaxis with
      high-dose TMP/SXT (320/1600 mg, daily) is preferred for renal transplant
      recipients during the first month posttransplantation.

PMID- 16980001
TI  - Interference of cyclosporine on glucose metabolism: potential role in chronic
      transplantation kidney fibrosis.
AB  - OBJECTIVES: To explore the fibrosis induction effects of cyclosporine (CsA) on
      renal tubular epithelial cells, as well as the potential mechanisms of CsA
      mediated alterations of glucose metabolism in chronic allograft nephropathy
      (CAN). METHODS: The rat renal tubular epithelial cell line NRK-52E cells were
      cultured in medium with 50 mmol/L of D-glucose for 7, 14, or 28 days. The
      expression of TGF-beta1, CTGF, Smad3, and Smad7, which are involved in the
      fibrosis signal pathway, was detected by immunofluorescence and reverse
      transcriptase polymerase chain reaction. Meanwhile, cells were cultured in
      various concentration of CsA in glucose-free medium for 24 hours followed by the
      addition of D-[3-(3)H]-glucose for 30 minutes; glucose uptake was detected by
      examining the radiation intensity. RESULTS: The expression of TGF-beta1, Smad3,
      Smad7, and CTGF of NRK-52E cells were up-regulated significantly (P < .05) after
      culture with 50 mmol/L glucose for 7 days compared with those in 25 mmol/L
      glucose. At 14 and 28 days, TGF-beta1 was slightly decreased compared with 7
      days, but CTGF, Smad3, and Smad7 increased robustly (P < .05). CsA significantly
      stimulated glucose uptake at various concentrations, with an absorption peak at
      60 minutes that decreased at 75 minutes. Furthermore, CsA may have dose-dependent
      effects on glucose uptake. CONCLUSION: High glucose concentrations may play an
      important role in the NRK-52E cell fibrosis during the CAN process due to an
      interference of CsA on glucose metabolism.

PMID- 16980002
TI  - 1,25-dihydroxyvitamin D(3) therapy is protective for renal function and prevents
      hyperparathyroidism in renal allograft recipients.
AB  - 1,25-Dihydroxyvitamin D(3) (calcitriol) therapy has been extensively used for
      posttransplant osteoporosis. Beside its effect on bone metabolism, calcitriol has
      an important immunomodulatory effect. We evaluated the effects of oral calcitriol
      therapy on allograft function and parathyroid hormone levels after renal
      transplantation. The patients were retrospectively selected from a renal
      transplant patient population who received calcitriol (group 1, n = 59, 36
      male/23 female, follow-up: 52.8 +/- 12.2 months) compared with group (group 2, n
      = 52, 42 male/9 female, follow-up: 62.0 +/- 24.4 months) without calcitriol
      therapy after renal transplantation. Calcitriol therapy was started 24.0 +/- 19.1
      months posttransplantation. All patients were under three-drug immunosuppression.
      The pretransplant and posttransplant data were studied retrospectively.
      Additionally, creatinine levels before and after the initiation of calcitriol
      therapy were recorded at 6 months intervals for 3 successive years. Our results
      were analyzed according to the first and third year on therapy data. According to
      the first year data, there were no differences in patient groups in terms of
      creatinine and iPTH levels. In the third year, the patients in group 1 showed
      significantly lower creatinine (P = .01) and iPTH (P < .04) levels and needed
      lower pulse steroid doses (P < .04). According to a Friedman repeated measures
      variance test, the creatinine level was significantly lower among group I (P <
      .04) at 3-year follow-up. In conclusion, even a delayed start of calcitriol
      therapy after renal transplantation exerts a protective effect on renal allograft
      function and prevents the development of hyperparathyroidism.

PMID- 16980003
TI  - Risk factors for changes in bone mineral density and the effect of
      antiosteoporosis management after renal transplantation.
AB  - Using the pretransplant bone mineral density (BMD) data records of renal
      recipients, we retrospectively examined risk factors affecting posttransplant
      changes in BMD and the effect of antiosteoporosis management. For 294 kidney
      transplant recipients from January 1996 to September 2003, BMD values were
      expressed as spine and femur T-scores. Gender, age, pretransplant diabetes, blood
      type compatibility, mode and duration of dialysis, and previous transplantation
      were considered to be variables affecting BMD changes. T-test or ANOVA was used
      to compare risk factors. At the time of transplantation, mean spine T-scores were
      significantly lower among the retransplant group. Mean femur T-scores were
      significantly lower among the retransplant group, older patients (older than 45
      years), and female recipients. Prolonged hemodialysis (>12 months) and
      retransplant were risk factors for BMD loss during the first year posttransplant.
      Early application of antiosteoporosis management was effective to ameliorate
      posttransplant BMD loss. However, antiosteoporosis management after 1 year
      posttransplant was relatively ineffective. Pretransplant evaluation of BMD and
      the possibility of significant BMD loss during the first posttransplant year
      should not be overlooked. Prophylaxis against bone loss and treatment should be
      started as soon as possible after transplantation for recipients with either
      normal or abnormal pretransplant BMD.

PMID- 16980004
TI  - Effects of azathioprine and mycophenolate mofetil-immunosuppressive regimens on
      the erythropoietic system of renal transplant recipients.
AB  - INTRODUCTION: Azathioprine (AZA) and mycophenolate mofetil (MMF) are major
      immunosuppressants used to prevent rejection following renal transplantation.
      Bone marrow suppression is a potential adverse effect of these agents manifesting
      itself as leukopenia, thrombocytopenia, and anemia. The aim of this study was to
      compare the effects of AZA versus MMF immunosuppressive regimens on the
      erythropoietic system of renal transplant recipients within 6 months after
      transplantation. METHODS: Eighty kidney allograft recipients who were on AZA (n =
      40) or MMF (n = 40) plus cyclosporine and prednisolone were enrolled in this
      study. Hematologic parameters included red blood cell counts, hemoglobin (Hb),
      hematocrit, mean corpuscular volume, mean corpuscular hemoglobin (MCH) and mean
      corpuscular hemoglobin concentration (MCHC) and were measured before and at 1
      week, as well as 1 and 6 months posttransplantation. Plasma erythropoietin level
      was measured at the end of 6 months. Statistical analysis was performed with
      Student t test; a P value less than .05 was considered significant. RESULTS:
      There was no significant difference between the two groups regarding red blood
      cell counts. High Hb level was noted at 1 and 6 months posttransplantation among
      patients who received MMF. MCH and MCHC were higher among patients on MMF
      compared with those on AZA at 1 week and 1 month posttransplant. Although the
      mean plasma erythropoietin levels in AZA-treated patients were higher than those
      of MMF-treated patients, the trend did not reach statistical significance (P =
      .066). CONCLUSION: MMF administration was apparently associated with a higher
      level of hemoglobin compared with AZA among renal allograft recipients with good
      graft function at 6 months posttransplantation.

PMID- 16980005
TI  - Hepatocellular carcinoma after renal transplantation: the long-term impact of
      cirrhosis on chronic hepatitis B virus infection.
AB  - Hepatocellular carcinoma (HCC) is the most common posttransplantation malignancy
      in hepatitis B virus (HBV) endemic areas. The aim of this study was to review the
      significant effect of liver cirrhosis on the outcome of renal allograft
      recipients with chronic hepatitis B. We performed a retrograde analysis of the
      clinical presentations of 66 hepatitis B surface antigen-positive kidney
      allograft recipients during the past 25 years with a mean follow-up of 76 months.
      Seven patients were diagnosed with HCC. The patients were subgrouped into
      cirrhotic versus noncirrhotic liver cohorts. Among renal allograft recipients
      with HBV infection, patients with cirrhotic livers had a higher risk of HCC (P =
      .003) and mortality (P = .025) than those with a noncirrhotic liver. The outcome
      was poor among the cirrhotic liver group. Pretransplantation liver biopsy may be
      indicated for the recipient candidate with HBV infection. Liver cirrhosis may be
      an exclusion criterion for the renal transplant waiting list due to the high
      incidence of HCC and the poor patient survival.

PMID- 16980006
TI  - Silent urothelial cancer detected by sonography after renal transplantation.
AB  - OBJECTIVES: Organ transplantation increases the incidence of cancer through
      unclear mechanisms. In our observation, urothelial cancer happens much more
      frequently in Chinese people. We reviewed the detection of urothelial cancer in
      our series after renal transplantation. METHODS: From July 1981 to June 2005, we
      performed 620 renal transplantations. We do graft and native kidney sonography
      survey annually even if the patient is asymptomatic. During this period, 10
      urothelial tumors were detected. Herein we have reviewed the findings in these
      cases, along with their management and outcomes. RESULTS: Moderate to severe
      hydronephrosis of native kidneys was observed in 14 patients, including 9 (64.3%)
      who had cancer including eight asymptomatic and only one with flank pain and
      lymph nodes metastasis succumbing in 10 months with a functioning graft. Three
      patients showed similar degrees of graft hydronephrosis and graft ureteral cancer
      was diagnosed in one. Mean time from transplantation was 5.09 years. There was a
      female predominance (7:3). The bladder-to-renal pelvis-to-ureter ratio was 2:5:7,
      which was distinct from the usual 51:3:1 distribution. In native ureter cancer,
      we found the left ureter more prone to develop cancer than the right (8:1).
      CONCLUSION: The pattern of cancer in renal transplant patients is thoroughly
      different from the general population, namely female predominance, with a higher
      incidence of ureteral and renal pelvis versus bladder cancer. In our observation,
      routine periodic sonography survey even in asymptomatic patients is important for
      urothelial tumor detection, as the incidence of cancer is surprisingly high.

PMID- 16980007
TI  - A case of benign retroperitoneal cyst of Mullerian type in kidney transplant
      patient.
AB  - Mullerian cysts of the retroperitoneum, which considered to be a subtype of
      urogenital cysts, are extremely rare disease entities. Herein we have presented
      successful excision from a second kidney transplantation from a brain-dead donor
      to a 38-year-old woman with previous kidney graft failure. During the second
      cadaveric kidney transplantation operation, two fist-sized cysts were found in
      the left retroperitoneal pelvic space extending from the left common iliac artery
      to the prevesical region, which compromised the iliac vessels for vascular
      anastomosis. After complete cyst excision, vascular anastomoses were performed.
      Histologically, the cysts were lined with benign Mullerian-type epithelium. We
      report a rare case of benign retroperitoneal cyst of the Mullerian type, which
      was incidentally found during kidney transplant surgery.

PMID- 16980008
TI  - Treatment of oropharyngeal cancer in renal transplant recipients without
      cessation of immunosuppressive therapy.
AB  - INTRODUCTION: Renal transplantation and immunosuppression are associated with an
      increased incidence of malignancy. Reduction or cessation of immunosuppressive
      therapy has been advocated in these cases to prevent tumor progression and
      recurrence. We evaluated the outcome of treatment of oropharyngeal cancer (OC)
      after renal transplantation without cessation of immunosuppressive therapy.
      METHODS: The database of patients with OC after renal transplantation was
      analyzed with respect to age, sex, type of immunosuppression, interval between
      transplantation and diagnosis of cancer, as well as method of treatment and
      survival. RESULTS: Thirty one (2.06%) renal transplant recipients developed
      malignancy including 6 (20%) with OC. Lingual cancer was seen in three, and one
      each showed an isolated tonsillar lymphoma, a parotid carcinoma, or a carcinoma
      of the larynx with only the last having had two other malignancies in the past.
      Three subjects were on immunosuppression with azathioprine and prednisolone, and
      the others were prescribed cyclosporine and prednisolone. Average time from
      transplantation to diagnosis of OC was 106 months. The interval was the shortest
      (2 years) for tonsillar lymphoma in an 18-year-old patient who received
      cyclosporine and showed features of left follicular tonsillitis. The patient with
      advanced carcinoma of the larynx did not receive any treatment and succumbed
      within 3 months. The dose of cyclosporine was reduced in the lymphoma case but
      immunosuppression was not altered in the other patients. All subjects were
      treated with a standard protocol. During a mean follow-up of 33 months, one had
      local recurrence of parotid carcinoma and the others showed well functioning
      renal grafts. CONCLUSION: Comprehensive treatment of OC after renal
      transplantation without withdrawing the immunosuppression prolonged the life of
      these patients with functioning grafts.

PMID- 16980009
TI  - Liver transplantation for hepatocellular carcinoma with bile duct thrombi.
AB  - In a few cases of hepatocellular carcinoma (HCC), jaundice results from
      obstructive causes, including tumor invasion or thrombi in the bile duct. We have
      reported herein our experience with liver transplantation (OLT) for HCC cares
      showing bile duct thrombi (BDT). From September 1996 to August 2004, 140 adult
      patients underwent OLT for HCC at our center. Four patients (2.9%) who had OLT
      performed for HCC had BDT and were included in this study. The patients were all
      men of mean age 57.0 years. The initial total bilirubin levels were in the range
      of 2.0 to 30.5 mg/dL. The sizes of the tumors ranged from 2.0 cm to 3.0 cm in
      diameter, all were single lesions. The median follow-up period was 20.6 months
      (range: 17.6 to 28.1 months). The only case in which the BDT was identified
      intraoperatively died 20 months after OLT due to multiple intrahepatic
      recurrences. The other three patients were alive, showing no evidence of
      recurrence at the end of follow-up. Although a series of four is too small to
      reach any conclusion, we suggest that OLT may be a treatment option for HCC with
      BDT in selected cases.

PMID- 16980010
TI  - Prognosis after liver transplantation predicted by preoperative MELD score.
AB  - The model for end-stage liver disease (MELD) has been an excellent predictor of 3
      month mortality among cirrhotic patients awaiting orthotopic liver
      transplantation (OLT). The aim of this study was to evaluate whether the
      preoperative MELD score predicts short-term prognosis after OLT. We enrolled 98
      adult liver transplant patients performed at our center from January 2001 to
      December 2002. In univariate analysis of risk factors for death within 3 and 6
      months after liver transplantation, serum total bilirubin, creatinine, MELD
      score, hyponatremia with ascites, Child-Turcotte-Pugh (CTP) score were
      statistically significant parameters (P < .05). By logistic regression, none of
      the risk factors were subjected to multivariate analysis showed statistical
      significance. The odds ratios of the MELD score, hyponatremia with ascites, CTP
      score within 3 months were 0.997, 1.151, and 0.726 with 95% confidence intervals
      of [0.899, 1.105], [0.102, 12.959], and [0.389, 1.352], respectively. The odds
      ratio of MELD score, hyponatremia with ascites, CTP score within 6 months were
      0.996, 0.914, and 0.764, with 95% confidence intervals of [0.901, 1.102], [0.089,
      9.369], and [0.417, 1.401], respectively. Although MELD score has been a good
      predictor of short-term prognosis before OLT, MELD did not show an influence on
      the short-term prognosis after liver transplantation in this study.

PMID- 16980011
TI  - MELD score as a prognostic model for listing acute liver failure patients for
      liver transplantation.
AB  - OBJECTIVES: The King's College Hospital (KCH) criteria are widely used for
      listing patients with acute liver failure (ALF) for liver transplantation (LT).
      Recent reports have suggested that the Model for End-Stage Liver Disease (MELD)
      score may be useful in assessing prognosis in ALF (nonparacetamol). This study
      compares prognostic accuracy of the two systems in patients with paracetamol
      (POD)-induced ALF treated in this unit. METHODS: Seventy-two patients (average
      age 38 years; F:M ratio 2:1) admitted from 1994 to 2005 with POD-related ALF were
      studied. Clinical and biochemical parameters were recorded. The effect of
      applying a MELD score of greater than 30 as listing criteria for LT was
      calculated and compared with the KCH criteria. Outcomes were defined as LT,
      death, or full recovery. RESULTS: Thirty-one patients (43%) recovered with
      medical therapy, 29 (40%) patients died, and 12 (17%) underwent LT. Sixty five
      percent of patients had a MELD > 30 and therefore could potentially be listed on
      admission; however, using KCH criteria only 24% patients were listed immediately.
      Sensitivity and negative predictive value of MELD was higher then KCH; however,
      we found KCH to have much higher specificity and positive predictive value.
      CONCLUSION: MELD has higher sensitivity and negative predictive value for POD
      induced ALF than the KCH criteria. However, the high false-positive rate
      associated with MELD limits its clinical utility. The high negative predictive
      value of MELD score may allow it to be used in conjunction with KCH criteria to
      avoid unneeded LT in patients who will likely recover spontaneously.

PMID- 16980012
TI  - Effect of middle hepatic vein reconstruction in living donor liver
      transplantation using right lobe.
AB  - BACKGROUND: This study reviewed the impact of middle hepatic vein (MHV)
      reconstruction on right lobe graft with regard to functional recovery and graft
      regeneration at 1 week after transplantation. MATERIALS AND METHODS: From January
      1999 to September 2005. 211 adult living donor liver transplantations were
      performed using the right lobe. The reconstruction of hepatic venous tributaries
      from segment 5 or segment 8 or both was performed in every cases of sufficient
      size. The patency of graft vessels was evaluated with computed tomography (CT)
      angiography on postoperative day 7. We analyzed liver enzymes (aspartate
      transferase [AST], alanine transferase [ALT] and bilirubin) at 1 week
      postoperatively and evaluated regeneration activity by CT volumetry at 1 week
      postoperatively. RESULTS: Among 211 cases, 182 (86.3%) were reconstructed with
      interpositional MHV grafts. Among them, 51 cases (51.9%) were patent at 1 week
      postoperatively. The levels of AST and ALT in patent cases of all patients and
      small-for-size grafts were lower than among the occlusion cases, albeit not
      significantly. The mean graft regeneration at 1 week postoperatively among patent
      cases was 1.75 +/- 0.39 versus 1.64 +/- 0.24 in the occluded cases (P = .111),
      but among small-for-size grafts, there was a significant difference in graft
      regeneration between patent versus occluded cases (2.05 +/- 0.50 vs 1.66 +/-
      0.17, P = .037). CONCLUSION: Functional recovery and graft regeneration in small
      for-size grafts showed a beneficial effect in patent cases, compared with
      occluded cases. Our selection criteria for MHV reconstruction must include cases
      of small-for-size grafts not all cases.

PMID- 16980013
TI  - Impact of liver donation on quality of life and physical and psychological
      distress.
AB  - Our objectives were to assess the characteristics of donors for living-donor
      liver transplantation (LDLT) and to examine the impact of donation on LDLT donor
      quality of life (QOL) regarding physical and psychological distress. METHODS:
      Data were collected from a mailed survey or an interview using a cross-sectional
      prospective study design. We used the abbreviated version of the World Health
      Organization Quality of Life (WHOQOL-BREF), Physical Symptom Disturbance Scale,
      and Psychological Distress Scale. LDLT donors were recruited from a teaching
      hospital located in a metropolitan area of northern Taiwan. RESULTS: The 35 LDLT
      donors have a mean age 34.0 +/- 8.6 years and were recruited at a median of 25.9
      months after donation (range, 0.6-92 months). The average scores in the four
      domains of the WHOQOL-BREF scale ranged from 13.5 to 14.9. LDLT Donors reported
      higher QOL scores in social and environment domains but lower scores in physical
      and psychological domains than healthy adults. Numbers of physical symptoms
      experienced by each donor ranged from one (n = 4) to 27 (n = 2). Feeling
      throbbing, itching or numbness around the wound was the most common physical
      symptom disturbance reported by donors (n = 26, 74%). Approximately 40% of the
      donors reported having one to three metrics of psychological distresses. "Easily
      feel distress and angry" was the most common psychological distress reported by
      57% (n = 20) of donors. CONCLUSIONS: This study indicated that liver donation had
      a mild negative impact on donors physical and psychological facets of QOL. These
      results may assist professionals to provide appropriate clinical management.

PMID- 16980014
TI  - Safety of donors with fatty liver in liver transplantation.
AB  - Steatotic liver graft transplantation affect donor safety as well as recipient
      survival. We investigated safety of donors according to the extent of fatty
      change. We retrospectively reviewed donors who underwent right hepatectomy from
      September 1999 to April 2005, dividing them into three groups according to degree
      of macrovesicular fatty change upon intraoperative liver biopsy. Group 1 included
      patients with macrovesicular steatosis of 0 approximately 9%: group 2, 10
      approximately 19% and group 3, at least 20%. Two hundred forty-five donors were
      enrolled with a male to female ratio of 2.02:1 and mean age of 31.8 years. There
      were 163 donors in group 1, 75 in group 2, and seven in group 3. There was no
      statistically significant difference in body mass index, operative time, blood
      loss, postoperative peak serum bilirubin, and aspartate transaminase levels among
      groups 1, 2, and 3. Overall complication rate, including reoperation, biliary
      stricture, wound infection, ileus, transfusion, bile leak and fluid collection
      were not different between the groups. Postoperative hospital stay was also not
      different. Peak alanine transaminase level was different between each group, and
      prothrombin time between group 1 and 3, but days until return to normal levels in
      all measured laboratory parameters were not different. Residual liver volume
      percent was significantly smaller among group 1 compared to others. In
      conclusion, fatty livers with less than 30% macrovesicular steatosis may be good
      donor candidates without significant complications as long as sufficient residual
      liver volume is left for the donor.

PMID- 16980015
TI  - Attitude toward living donor liver transplantation in Taiwan.
AB  - OBJECTIVES: The purpose of this study was to investigate the attitudes and
      characteristics of donors for living donor liver transplantation (LDLT). METHODS:
      This retrospective study was performed by a mailing or by telephone using a
      questionnaire. LDLT donors were recruited from a teaching hospitals located in a
      metropolitan area of northern Taiwan. The 11-item attitude questionnaire was
      specifically developed from the literature review with coordinator, physician,
      and donor feedback. Donors were asked to rate the queries on a 5-point Likert
      intensity scale. RESULTS: The 47 LDLT donors included 28 (60%) women and 19 (40%)
      men. Most of the LDLT donors were aged less than 30 years old (n = 24, 51%) with
      (n = 12, 26%) between 31 and 40 years, and 11 (23%) more than 41 years. Self
      perceived health status was poor (n = 4, 9%), not bad (n = 22, 47%), good (n =
      19, 40%), or very good (n = 2, 4%). The top five LDLT donor attitudes were
      recognition of liver donation (n = 42, 89%), recognition of brain donation (n =
      41, 88%), a hero (n = 35, 75%), honor to be a donor (n = 35, 5%), and improved
      relationship with recipient after donation (n = 33, 70%). The best person to
      suggest organ donation to a family was ranked as the doctors related to
      transplantation (n = 41, 88%), transplantation nurse coordinator (n = 40, 85%),
      social worker (n = 23, 49%), and doctor unrelated to transplantation (n = 17,
      17%). CONCLUSION: This study revealed positive attitudes toward donation. Some
      data afford insight to the decision-making procedure. Donor concerns may help
      professionals provide better interventions in the future.

PMID- 16980016
TI  - Liver transplantation: experience at our center.
AB  - Liver transplantation was pioneered by Starzl and his team in 1967. Since then,
      many difficulties have been overcome and this treatment modality has gained
      worldwide acceptance as the definitive treatment for end-stage liver disease.
      However, the current numbers of liver transplantations are still far below what
      is needed, the rising numbers on waiting lists have pushed transplant surgeons to
      search for new alternatives, and living related donors are considered one
      solution. At our center, the only living liver donors we accept are relatives and
      spouses of recipients. We have held the same policy for our kidney program from
      the beginning. In the past 3 years, we have increased the annual numbers of liver
      transplantations; our graft and patient survival rates for this period exceed
      90%. Liver grafts donated by living related donors offer an extremely important,
      lifesaving alternative in urgent situations, such as acute liver failure, where
      there is limited time to wait for a deceased donor. Hepatocellular carcinoma is
      another important indication for living related liver transplantation.
      Availability of living donors allows us to perform transplantations even in
      recipients with advanced tumors who would not be accepted as appropriate
      transplant candidates according to widely used selection criteria. Liver
      transplantation is a lifesaving procedure that presents many challenges, and our
      experience has led us to develop an innovative technique for biliary
      reconstruction. We have used a method of "back-table guide-wire placement and
      intraoperative transhepatic biliary catheter insertion" in 44 patients since
      December 2004 to significantly decrease biliary complications and perform duct-to
      duct anastomosis even in small pediatric recipients.

PMID- 16980017
TI  - Adult living donor liver transplantation using the right lobe.
AB  - BACKGROUND: This article reviewed our experience with right lobe donor
      hepatectomy in living donor liver transplantations (LDLT), particularly in the
      context of preserving donor safety. MATERIALS AND METHODS: From January 2000 to
      August 2005, we performed 206 adult LDLT operations using the right lobe. The
      donor characteristics, operative findings, postoperative results including the
      peak values of liver enzymes (aspartate transferase [AST], alanine transferase
      [ALT], and bilirubin) and regeneration volumes, as evaluated by computed
      tomography volumetry, were reviewed at 1 week, as well as 3 and 6 months after
      surgery. The effects of three risk factors on donor safety were analyzed: age
      (<55 years, > or =55 years): fatty change in the donor liver (<10%, > or =10%);
      and remnant volume (<35%, > or =35%). RESULTS: The liver enzymes and regeneration
      volumes showed no significant difference according to age, only ALT was
      significant increased associated with the severity of fatty change (P < .05).
      There were significant differences in postoperative AST, ALT, and regeneration
      volume between the group with <35% and the group with > or =35% remnant liver
      volume (P < .05). Upon further analysis with combinations of two out of three
      risk factors, the group according to remnant volume and fatty change was
      meaningful. Follow-up data on donor ALT showed a return normal levels and after
      postoperative 3 months there was regeneration of the remnant liver to more than
      70% of the whole liver preoperatively. There was no donor mortality, but
      postoperative complications were observed in 39 patients (39/206, 18.9%). Biliary
      complications were encountered in 24 patients: one bile duct injury, 22 bile
      leakages, and one bile duct stricture. Other complications consisted of pleural
      effusion (n = 8), delayed gastric emptying (n = 6), atelectasis (n = 1), and
      hepatic encephalopathy (n = 1). CONCLUSION: In cases of careful donor selection,
      a right lobectomy can be performed safely with minimal risks when the remnant
      liver volume exceeds 35% of the total liver volume and shows less than 10% fatty
      changes.

PMID- 16980018
TI  - Outcome of patients with recurrent hepatocellular carcinoma in liver
      transplantation.
AB  - Liver transplantation (OLT) is the treatment of choice for patients with hepatic
      cirrhosis related hepatocellular carcinoma (HCC). Among 156 liver transplant
      patients for HCC from June 1996 to February 2005, 23 had recurrent HCC. To
      evaluate risk factors that affect early recurrence of HCC after OLT, we divided
      the 23 patients into two groups: early (< or =12 months) and late (>12 months)
      recurrences. Among them, 15 patients were dead and eight alive patients had been
      followed to 31 July 2005. The most common recurrence site was the grafted liver
      (n = 15), next was bone (n = 11), lung (n = 8), lymph node (n = 6), brain (n =
      4), skin (n = 2), adrenal gland (n = 1). There were no significant differences
      between the two groups in age or tumor size, number of tumors, cell
      differentiation, alpha-feto protein levels, tumor staging, number of patients
      within Milan criteria, steroid pulse therapy, infectious diseases, and
      immunostaining of tumor. In our study, there were no risk factors that predict
      early tumor recurrence. We noticed that more patients in the early recurrence
      group were excluded by Milan criteria due to a more progressed tumor staging with
      higher mean levels of serum alpha-feto protein.

PMID- 16980019
TI  - Outcomes of hepatitis B virus recurrence after liver transplantation.
AB  - The introduction of high doses of hepatitis B immune globulin (HBIG) and
      lamivudine for liver transplantation (OLT) prophylaxis has reduced the risk of
      hepatitis B recurrence and improved the survival of patients transplanted for
      hepatitis B virus (HBV)-related liver disease. But, posttransplant prophylaxis
      strategies to treat the recurrence of HBV have not yet been standardized. We
      analyzed 23 patients with HBV recurrence among 340 HBV-associated liver
      transplants performed from September 1996 to April 2004 (6.7%). Nine patients
      underwent deceased donor OLT and 14, living donor OLT. Mean follow-up was 37
      months. Seroconversion after recurrence was observed in 6 of 23 patients (26%).
      Mean time to HBV recurrence tended to be shorter among the seroconversion (+)
      patients compared to seroconversion (-) patients (10 months vs 19.7 months; P =
      .062). Seroconversion rate after HBIG and lamivudine combination therapy for
      patients with HBV recurrence was 37.5% and time to seroconversion after HBV
      recurrence was 1.7 months. Seroconversion was best achieved when the
      pretransplant HBV DNA level was high and HBeAg was positive. Also, seroconversion
      rate was increased when HBV DNA level was low and the alanine transferase level
      high at the time of recurrence and when the time to recurrence after
      transplantation was short. Seroconversion after HBV recurrence, which was
      observed in 26%, may be increased in selected cases. Accordingly, aggressive
      treatment should be undertaken after HBV recurrence.

PMID- 16980020
TI  - Extracorporeal membrane oxygenation hybrid with various ventricular assist
      devices as double bridge to heart transplantation.
AB  - Ventricular assist devices (VAD) have benefitted patients with end-stage heart
      failure as a bridge to heart transplantation (HTx). We present our experience
      with HTx after an extracorporeal membrane oxygenation (ECMO) hybrid with various
      ventricular assist devices (VAD). From May 1996 to December 2003, mechanical
      circulatory support with a Biopump VAD was performed in eight patients, HeartMate
      left VAD in eight patients, and Thoratec VAD in eight patients. Before VAD
      implantation, 19 patients maintained their circulation with ECMO. Half of the 24
      patients were implanted with VAD to await a suitable donor for HTx. We observed
      that half of the patients supported by ECMO hybrid with various VAD awaited a
      suitable donor for HTx. In our experience, we recommend the application of ECMO
      for short-term support within 1 week and the Biopump VAD, Thoractec VAD, or
      HeartMate VAD for medium-term or long-term support as a bridge to HTx.

PMID- 16980021
TI  - Single-center experience of pediatric heart transplantation in taiwan.
AB  - Heart transplantation (HTx) is a treatment for end-stage heart failure or a
      complex or inoperable congenital defect. The long-term survival and the adequate
      donor to recipient body weight (D/R BW) ratio remain to be determined. From March
      1995 to May 2004, 14 children (6 months-16 years of age) underwent HTx due to
      underlying diseases of idiopathic dilated cardiomyopathy (n = 10; 71.4%),
      congenital heart disease (n = 3; 21.4%), and Kawasaki disease (n = 1; 7.1%).
      Donor-recipient body weight ratio ranged from 0.89 to 3.9. Big heart syndrome was
      present in one patient when D/R BW ratio was more than 3. Actuarial survival was
      92.9% at 5 years after transplantation. Only the one patient who had Kawasaki
      disease died due to early primary graft failure. HTx is a feasible method with
      good long-term survival rates for end-stage heart failure or for complex or
      inoperable congenital defects. After careful pretransplant evaluation, a high D/R
      BW ratio (more than 3) is acceptable.

PMID- 16980022
TI  - Therapeutic drug monitoring of cyclosporine Neoral in de novo Chinese cardiac
      transplant recipients treated with an everolimus-cyclosporine immunosuppressive
      regimen.
AB  - This study determined cyclosporine Neoral (CsA) pharmacokinetics and the accuracy
      of a limited sampling strategy to predict the 12-hour CsA area-under-the-curve
      (AUC) to provide a practical method for more accurate therapeutic drug monitor of
      CsA among de novo Chinese heart transplant recipients treated with an everolimus
      CsA immunosuppressive regimen. METHODS: Blood samples were collected at 0, 0.5,
      1, 2, 3, 4, 6, 8, 10, and 12 hours after oral administration of CsA in six de
      novo heart recipients receiving a CsA, everolimus, and methylprenisolone
      immunosuppressive regimen after rabbit antithymoglobulin sequential immuno
      induction. We analyzed the pharmacokinetics of the first dose (PK-1) and steady
      state dose (PK-2) at 1 month after transplantation. The accuracy of a single
      point sampling method to predict the AUC was generated by linear regression
      analyses. RESULTS: The t(max) and dose-normalized C(max) of PK-1 and PK-2 were
      similar. The correlations in single-point blood levels of PK-1 to predict the
      AUC(0-infinity) were much lower than the corresponding sampling times in PK-2. In
      PK-2 study, C4 had the best correlation (r(2) = 0.913, P = .003) to predict AUC(0
      12). In addition, the trough concentrations, C(0) (r(2) = 0.875, P = .006) and
      C(12) (r(2) = 0.783, P = .02) also showed good correlations. C2 had insufficient
      correlation to predict AUC(0-infinity) in PK-1 or AUC(0-12) in the PK-2 study. In
      conclusion, the absorption of CsA was similar during PK-1 and PK-2. At steady
      dose, C4 had the best single-point correlation to predict AUC(0-12). Trough blood
      levels may be more practical in clinical use to monitor CsA.

PMID- 16980023
TI  - Simultaneous heart and kidney transplantation for combined cardiac and renal
      failure.
AB  - Simultaneous heart and kidney transplantation (SHKT) is feasible for combined
      cardiac and renal failure. Herein we reviewed our 10-year experience in SHKT. Six
      patients underwent SHKT from June 1995 to December 2004. Their ages ranged from
      13 to 63 years old with a mean of 45.5 +/- 15.8 years. They were all men except
      one girl, who was the youngest (aged 13) who suffered from dilated cardiomyopathy
      with congestive heart failure and chronic renal failure due to systemic lupus
      erythematosus. Because of aggravating heart failure, she changed from
      hemodialysis to peritoneal dialysis. Because of intractable heart failure, she
      underwent SHKT from a 24-year-old female donor. All received hemodialysis before
      SHKT. The indications for heart transplantation included dilated cardiomyopathy
      (n = 3), ischemic cardiomyopathy (n = 1), cardiac allograft vasculopathy (n = 1),
      and cardiac allograft failure (n = 1). The immunosuppressive protocol and
      rejection surveillance were these employed for heart transplantation. No
      operative mortality was noted in this study. The 1-year and 5-year survival rates
      were the same, 83%. The 10-year survival rate was 55%. No cardiac or renal
      allograft rejection was noted. No renal allograft loss was noted. There were two
      late mortalities: the one, who underwent redo heart transplantation for coronary
      artery vasculopathy died of cardiac allograft failure 1 year after SHKT. The
      other patient died of massive ischemic necrosis of the intestine at 6 years after
      SHKT. Our experience showed that SHKT had good short- and long-term results
      without increasing immunosuppressive doses. End-stage failure of either the heart
      or the kidney did not preclude heart plus kidney transplantation.

PMID- 16980024
TI  - Successful treatment of hepatitis B virus infection with Lamivudine after heart
      transplantation.
AB  - Patients with hepatitis B virus (HBV) infection have a higher morbidity and
      mortality after heart transplantation (HT). HBV infection is endemic in Taiwan.
      We studied the effect of lamivudine treatment of HBV infection after HT. From
      July 1987 to July 2005, 252 patients underwent HT. All recipients and donors
      underwent routine screening of hepatitis B surface antigen (HBsAg), hepatitis B e
      antigen, antibody to hepatitis B surface antigen, antibody to hepatitis B core
      antigen, antibody to hepatitis B e antigen, and an alanine aminotransferase (ALT)
      level before HT. When ALT was two times greater than the upper limit of normal or
      serum bilirubin was higher than 3 mg/dL in HBsAg-positive patients, HBV-DNA were
      checked by a branched DNA assay or polymerase chain reaction. When HVB-DNA was
      greater than 100,000 copies/mL, lamivudine (100 mg per day) was prescribed
      indefinitely. There were 14 patients under lamivudine treatment after HT, among
      whom, none suffered severe adverse reactions from lamivudine. Four patients died:
      one due to end-stage cirrhosis while awaiting liver transplantation at 14 months
      after HT. Two died of sudden death at 54 months and 138 months after HT. Another
      died of diffuse B cell lymphoma at 62 months after HT. All the survivors have
      normal ALT and undetectable HBV-DNA after lamivudine treatment. But the YMDD
      mutant was detected in two patients. With successful treatment of HBV infection
      in HT, it is not necessary to exclude HBV infection patients from HT.

PMID- 16980025
TI  - Bone mineral density in long-term Chinese heart transplant recipients: a cross
      sectional study.
AB  - Osteoporosis, which usually peaks during 6 to 12 months after transplantation,
      remains an important concern after heart transplantation. Immunosuppressants
      contribute to this phenomenon. Glucocorticoids are well documented to cause bone
      loss, but the role of cyclosporine (CsA) remains controversial, especially among
      long-term recipients on low doses of steroid. We herein report a cross-sectional
      study of bone mineral density (BMD) among long-term Chinese heart transplant
      recipients. We enrolled 41 patients of mean age 50.15 +/- 13.58 years with a mean
      follow-up of 57.02 months. Lumbar spine and femoral neck BMD were measured by
      dual energy x-ray absorptiometry. Trough CsA levels (C(0)) and markers of mineral
      metabolism, including bone-specific alkaline phosphatase and urinary N
      telopeptide, were determined by immunoassay. Sixty six percent of subjects showed
      bone loss at the femoral neck, significantly more than those in the lumbar spine.
      Those receiving a higher CsA dosage (<2.5 mg/kg/d) showed greater femoral neck
      BMD, but lower serum creatinine values. Our results demonstrated that bone loss
      remains long after transplantation, though bone markers are within normal limits.

PMID- 16980026
TI  - Sparing immunosuppression in heart transplant recipients with severe sepsis.
AB  - This study described an analysis of severe sepsis among heart transplantation
      recipients who were treated by sparing all immunosuppressants. Sepsis leading to
      multiple organ failure (MOF) in heart transplantation has a high mortality. This
      retrospective study of 190 patients who underwent heart transplantation from 1993
      to 2004 included 12 who had severe sepsis with MOF who were treated by sparing
      all immunosuppressants. Half of them survived after sparing all
      immunosuppressants with intensive endomyocardial biopsy. Only one case needed
      pulse therapy for an acute rejection episode. The most common bacterial
      infectious episodes were caused by methicillin-resistant Staphylococcus aureus (n
      = 3). All sepsis episodes occurred in the first month after heart transplantation
      except in one case, which occurred 6 years after heart transplantation. There was
      a 50% survival rate of heart transplantation recipients who experienced MOF due
      to severe sepsis and were treated by sparing all immunosuppressants under a
      program of intensive endomyocardial biopsy.

PMID- 16980027
TI  - Heart retransplantation for heart allograft failure in Chinese heart transplant
      recipients: NTUH experience.
AB  - We investigated the short- and long-term results after heart retransplantation in
      terms of different causes of heart allograft failure. We sought to establish the
      data of heart retransplantation in Chinese compared with Western counterparts due
      to differences in heart allograft vasculopathy. From March 1995 to May 2005,
      eight heart transplantation recipients with allograft failure underwent
      retransplantation. Heart allograft failure was due to coronary vasculopathy (CAV)
      in six patients (75%) and acute rejection in two patients (25%). The mean
      interval to retransplantation was 32 to 84 months (mean 54.3 months). There were
      five patients who survived after heart retransplantation for CAV and no patient
      survived after an earlier diagnosis of acute rejection. Heart retransplantation
      is a feasible method with acceptable long-term survival rate for heart allograft
      failure. After careful pretransplant evaluation, retransplantation is acceptable.
      The survival after retransplantation for CAV is notably great than that after
      acute rejection. Heart retransplantation is the only way for patients who have
      cardiac allograft failure to achieve long-term survival.

PMID- 16980028
TI  - Selective depletion of activated T cells by recombinant immunotoxin containing
      anti-CTLA-4 single-chain fragment of variable antibody and N-terminal fragment of
      perforin.
AB  - We constructed a novel immunotoxin, hS83P34, by fusing the fragment containing
      the N-terminal 34 amino acids of human perforin to the C-terminal of humanized
      anti-CTLA-4 single chain fragment of variable antibody. In vitro cytotoxicity
      assays demonstrated that CTLA-4-positive activated human T cells and 6T-CEM were
      sensitive to hS83P34, while CTLA-4-negative resting T cells and endothelial cell
      ECV-304 were resistant to hS83P34. The IC50s of hS83P34 for activated T cells and
      6T-CEM were about 0.2 micromol/L and 1.0 micromol/L, there was no obvious
      cytotoxicity of ECV-304 as detected at 8 micromol/L of hS83P34. In tumor graft
      rejection models, after treatment with 1.2 mg/kg immunotoxin every day for 12
      days, the transplanted tumor cells were rescued by immunotoxin. The tumor weights
      of grafts of the rejection control group, nonrejection control group, and test
      group were 0.006 +/- 0.014 g, 0.261 +/- 0.048 g, and 0.135 +/- 0.056 g,
      respectively. In the early 3 days posttransplantation, there were a lot of CD4-
      and CD8-positive T cells infiltrating into the tumor grafts of the rejection
      control group, while only a few T cells were detected in the tumor grafts of the
      test group. According to these results, we concluded that immunotoxin hS83P34
      selectively depleted activated T cells in vitro as well as in vivo in an acute
      rejection model.

PMID- 16980029
TI  - The effects of different immunosuppressants on chronic allograft nephropathy by
      affecting the transforming growth factor-beta and Smads signal pathways.
AB  - OBJECTIVE: This study investigated the effects of various immunosuppressants on
      chronic allograft nephropathy (CAN) by affecting transforming growth factor-beta
      (TGF-beta) and Smads signal pathway. METHODS: Vascular smooth muscle cells (VMSC)
      from rat aorta were incubated for 6 or 12 hours with various immunosuppressants.
      Cyclosporine (CsA) (3 microg/mL), FK506 (1 microg/mL), mycophenolate mofetil
      (MMF) (0.3 microg/mL), rapamycine (Rapa) (10 microg/mL), CsA (1 microg/mL/MMF 0.3
      microg/mL). We used the Sprague-Dawley Wistar rat accelerated kidney sclerosis
      model. Before transplantation, the kidney was preserved 1 hour in 0 degrees C to
      4 degrees C heparin sodium chloride solution to reinforce the cold ischemia
      injury. The rats were divided into eight groups (each group n = 8): group A,
      pseudo-OP; group B, isotransplantation; group C, CsA 6 mg/kg . d; group D, FK506
      0.15 mg/kg . d; group E, MMF 20 mg/kg . d; group F, Rapa 0.8 mg/kg. d; group G,
      CsA 3 mg/kg . d + MMF 20 mg/kg . d. The serum creatinine levels and pathological
      changes, according to the Banff scheme, were observed at 2, 4, 6, 8 and 12 weeks
      posttransplantation. Immunohistochemistry and quantitative fluorescence
      polymerase chain reactions were used to end localize and quantitate the
      expression of TGF-beta1 and Smad 2, 3, 7 in VMSC and in the transplanted kidney.
      RESULTS: CsA and FK506 stimulated gene expression and protein production of TGF
      beta1, smad2, and smad3, but inhibited expression of smad7 both in VSMC and in
      the transplanted kidney. In contrast, MMF and Rapa down-regulated gene expression
      and protein production of TGF-beta1, smad2, 3 while up-regulating expression of
      smad7. There was no significant difference between the CsA group and the FK506
      group, as well as the MMF group and the Rapa group. The group treated with CsA +
      MMF was similar to the MMF and the Rapa groups. CONCLUSION: Our study suggested
      that various immunosuppressants affected differentially TGF-beta1 and Smads
      signal pathways in rat VSMC and kidney grafts. CsA and FK506 can cause CAN, owing
      to up-regulated expression of smad2 and smad3, and down-regulation of smad7
      expression. MMF and Rapa can prevent the CAN progression, because of down
      regulation of the expression of smad2 and smad3, with increased smad7 production.

PMID- 16980030
TI  - Nuclear translocation of SMAD3 may enhance the TGF-beta/SMADS pathway in high
      glucose circumstances.
AB  - OBJECTIVES: Posttransplant diabetes mellitus is one of the most frequent
      complications after kidney transplantation. It is considered to be one cause of
      chronic allograft nephropathy. This study sought to investigate the effects of
      high glucose on the expression and nuclear translocation of Smad3, which is an
      important signal mediator involved in the fibrotic signal pathway. METHODS: The
      established rat renal mesangial cell line HBZY-1 was cultured in medium with
      various concentrations of glucose (4.5 mg/mL, 9.0 mg/mL, or 13.5 mg/mL), which
      was collected at 7, 14, or 21 days. The total expression of Smad3, including both
      inner and outer nucleus proteins was examined by Western blot analysis. The
      nuclear translocated Smad3, representing only the inner nucleus protein, was
      detected by immunofluorescence staining observed under a laser confocal scanning
      microscope. RESULTS: No significant difference in the total Smad3 expression was
      demonstrated by Western blot analysis among the three groups of HBZY-1 cells at
      various concentration of glucose after 7, 14, or 21 days. There was no
      fluorescence detected in the nucleus at day 7 by immunofluorescence staining;
      however, robust positive expression of Smad3 was detected at days 14 and 21.
      CONCLUSION: As a restricted Smads member, Smad3 protein might not be upregulated
      in the presence of high glucose. However, with prolonged culture time, Smad3
      translocates from cytoplasm to nucleus, which may be a pivotal step in the
      fibrotic signal pathway.

PMID- 16980031
TI  - Effect of AP-1 decoy using hemagglutinating virus of Japan-liposome on the
      intimal hyperplasia of the autogenous vein graft in mongrel dogs.
AB  - Intimal hyperplasia is the leading cause of late vein graft failure. Smooth
      muscle cell proliferation and migration is the underlying mechanism.
      Pharmacological approaches to prolong vein graft patency have produced limited
      results. AP-1 proteins play a role in the expression of many genes involved in
      cellular proliferation and cell cycle progression. Previously we reported
      inhibition of vascular smooth muscle cell migration, proliferation, and intimal
      hyperplasia in the balloon-injured rat carotid artery using an AP-1 decoy with
      HVJ-liposomes. In this report, we evaluated the effect of the AP-1 decoy on
      intimal hyperplasia in a large animal model. The jugular vein was transfected
      with hemagglutinating virus of Japan-liposomes containing the AP-1 decoy or
      scrambled oligonucleotides. An interposition graft was performed with the
      pretreated jugular vein between the transected femoral arteries. The graft was
      harvested at 16 weeks after the procedure. The intimal area was compared: the
      intimal area of the AP-1 decoy-treated versus control group was 47.3 +/- 15.2
      versus 102.3 +/- 15.9 (P < .05), respectively. In conclusion, AP-1 decoy using
      HVJ-liposomes effectively prevented intimal hyperplasia of an autogenous vein
      graft in mongrel dogs.

PMID- 16980032
TI  - Conversion from cyclosporine to mycophenolate mofetil improves expression of A20
      in the rat kidney allografts undergoing chronic rejection.
AB  - AIMS: Cytoprotective genes have shown to display potent anti-inflammatory and
      antiapoptotic functions in endothelial and smooth muscle cells. We investigated
      whether cytoprotective genes, especially A20, were involved in mycophenolate
      mofetil (MMF)'s ability to ameliorate transplant arteriosclerosis in an
      experimental chronic rejection model. METHODS: Sprague-Dawley rat renal grafts
      were orthotopically transplanted into Wistar rats following the procedure of
      Kamada with our modification. The recipients were divided into three oral
      treatment groups: (1) vehicle group (cyclosporine [CsA] 10 mg/kg.d x 10 d
      followed by vehicle), (2) CsA group (CsA 10 mg/kg.d x 10 d followed by CsA 6
      mg/kg.d), (3) MMF group (converted from CsA 10 mg/kg.d x 10 d to MMF 20 mg/kg.d
      on day 11). At the same time points after transplantation, the rats were
      sacrificed to harvest the renal allografts. The expression of four cytoprotective
      genes, A20, heme oxygenase (HO)-1, Bcl-2, and Bcl-XL, was analyzed by
      quantitative reverse-transcriptase polymerase chain reaction and
      immunohistochemistry. RESULTS: The four-cytoprotective genes were all detected in
      rat kidney allografts undergoing chronic allograft nephropathy. The expression of
      A20 in grafted kidneys was significantly higher in the MMF than in the CsA or the
      vehicle group (P < .01). There was no significant difference between the CsA and
      the MMF groups in the expression of HO-1, Bcl-2, and Bcl-XL. CONCLUSIONS: We
      demonstrated that MMF improved the expression of A20 in rat kidney allografts
      undergoing chronic allograft nephropathy. The correlation between MMF and A20
      provide an explanation for the mechanism by which MMF ameliorates transplant
      arteriosclerosis in an experimental animal model of chronic rejection.

PMID- 16980033
TI  - Expression of H60 on mice heart graft and influence of cyclosporine.
AB  - OBJECTIVES: It has been reported that the MHC class I chain-related antigen
      (MIC), a ligand of NKG2D, an activating receptor of natural killer cells, is
      expressed on rejected renal allografts. This study investigated whether heart
      transplantation induced expression of a homologue of MIC (H60) in outbred Kun
      Ming (KM) mice, widely used in China, and whether CsA had an influence on the
      process. METHODS: Forty-eight KM female mice were divided into untreated and CsA
      treated groups, after cervical heart allotransplantation. Grafts were harvested
      1, 3, 5, and 7 days postoperatively. H60 mRNA was analyzed by RT-PCR, and the
      protein detected by immunohistochemistry. RESULTS: Compared with no mRNA
      expression in the normal heart, H60 mRNA was observed at day 5 and upregulated on
      day 7 in the untreated group. It was detected on day 3, peaked on day 5, but was
      lower than untreated group, and decreased on day 7 in the CsA-treated group. H60
      protein was detected in cardiocytes only on day 7 in the untreated group.
      CONCLUSION: Our study suggested that expression of the NKG2D ligand, H60, may
      activate natural killer cells playing a significant role in innate immunity
      associated with transplantation. The early expression of H60 mRNA on day 3 in the
      CsA-treated group might relate to the toxicity of CsA. The expression peaked on
      day 5 and decreased on day 7, possibly induced by CsA. The results suggested that
      H60 might be a new target for prevention of rejection.

PMID- 16980034
TI  - Comparison of rapamycin versus FK506 on expression of cytoprotective genes in the
      rat kidney allografts undergoing chronic allograft nephropathy.
AB  - AIMS: It is increasingly recognized that expression of cytoprotective genes in
      grafts can affect the progress of chronic allograft nephropathy (CAN). Little is
      known about the influence of different immunosuppressive regimens on expression
      of cytoprotective genes in allografts undergoing CAN. We investigate whether
      there is difference between rapamycin (Rapa) and FK506 in the expression of
      cytoprotective genes in rat kidney allografts undergoing CAN. METHODS: Sprague
      Dawley rat renal grafts were orthotopically transplanted into Wistar rats
      following the procedure of Kamada with our modification. The recipients were
      divided into three oral treatment groups: group 1: vehicle group (cyclosporine
      [CsA] 10 mg/kg.dx 10 days followed by vehicle); group 2: Rapa group (CsA 10
      mg/kg.d x 10 d followed by Rapa 0.8 mg/kg.d); group 3: FK506 group (CsA 10
      mg/kg.d x 10 d followed by FK506 0.15 mg/kg.d). At the same times after
      transplantation, the rats were sacrificed to harvest the renal allografts. The
      expression of four cytoprotective genes, A20, heme oxygenase (HO)-1, Bcl-2, and
      Bcl-X/L were analyzed in these grafted kidneys by quantitative reverse
      transcriptase polymerase chain reaction and immunohistochemistry. RESULTS: Four
      cytoprotective genes were all detected in rat kidney allografts undergoing CAN.
      The expression of A20 in the Rapa group was significantly higher than that in the
      FK506 or the vehicle group (P < .05). There was no significant difference between
      the Rapa group and FK506 group in the expressions of HO-1, Bcl-2, and Bcl-X/L.
      CONCLUSIONS: We demonstrate that various immunosuppressive agents have different
      effects on the expression of cytoprotective genes.

PMID- 16980035
TI  - Expression of renal transforming growth factor-beta and its receptors in a rat
      model of chronic cyclosporine-induced nephropathy.
AB  - OBJECTIVE: We sought to detect expression of transforming growth factor-beta 1
      (TGF-beta1) as well as its receptors type I (TRI) and type II (TRII) in rat
      kidneys during chronic cyclosporine (CsA)-induced nephropathy. METHODS: Twenty
      four rats were randomly divided into three experimental groups: group 1; NSD
      (control, n = 8) were administered a normal sodium diet, group 2; LSD (n = 8)
      were administered a low sodium diet, group 3; CsA (n = 8) were sodium-depleted
      rats administered Neoral by gastric gavage in a model of chronic CsA-induced
      nephropathy. TGF-beta1, TRI, and TRII proteins, as well as TRI and TRII mRNAs
      were measured in the CsA-treated rat kidneys by immunohistochemistry and in situ
      hybridization, respectively. Semiquantitative results were shown by image
      analysis. RESULTS: The expression of TGF-beta1, TRI, TRII, TRI mRNA, and TRII
      mRNA were all increased in CsA-treated rat kidneys, compared with NSD or LSD (P <
      .05). CONCLUSION: Our study showed that the ligand of TGF-beta1 and its receptors
      TRI, TRII were all up-regulated. It may be important to inhibit the expression of
      TGF-beta1 or its receptors in patients who suffer from chronic CsA-induced
      nephropathy.

PMID- 16980036
TI  - Comparison of expression of TGF-beta1, its receptors TGFbeta1R-I and TGFbeta1R-II
      in rat kidneys during chronic nephropathy induced by cyclosporine and tacrolimus.
AB  - OBJECTIVE: Chronic rejection is a major cause of graft dysfunction after kidney
      transplantation. Long-term treatment with cyclosporine (CsA) or tacrolimus
      (FK506) results in chronic nephrotoxicity. Transforming growth factor-beta1
      (TGFbeta1) and its receptors type I (TR-I) and type II (TR-II) have been known to
      contribute to this side effect. The expression of TGF-beta1, TR-I, and TR-II in
      rat kidneys has not been compared during chronic nephropathy induced by CsA or
      FK506. METHODS: Rat models of chronic CsA- or FK506-induced nephropathy were
      established using Sandimun Neoral or Prograf administration. The kidneys were
      dissected and TGF-beta1, TR-I, and TR-II proteins and TR-I and TR-II mRNAs
      measured by immunohistochemistry and in situ hybridization, respectively, to
      compare the results of the two groups. RESULTS: The functional and morphologic
      studies showed that in the rats the nephrotoxic effects of FK506 were not as
      significant as those of CsA. The results of immunohistochemistry and in situ
      hybridization showed that the expression of renal TGFbeta1, TR I, TR-II proteins
      and TR and TR II mRNA in the FK506 group were lower than those in the CsA groups.
      CONCLUSION: These results showed that both FK506 and CSA display nephrotoxicity,
      but that the nephrotoxicity of FK506 was less than that of CsA in chronic
      nephropathy.

PMID- 16980037
TI  - Impact of Lotensin and Salviae on the changes of TGF-beta1 and its receptors in a
      rat model of chronic cyclosporine-induced nephropathy.
AB  - OBJECTIVES: Transforming growth factor-beta(1) (TGF-beta(1)) and its receptors,
      type 1 (TR-1) and type 2 (TR-2) play important roles in chronic cyclosporine
      (CsA)-induced nephropathy. Lotensin is known as an angiotensin-converting enzyme
      inhibitor and may reduce chronic CsA-induced nephropathy. Recently it is reported
      that Salviae (a Chinese medicine), which can improve microcirculation and
      decrease the expression of TGF-beta(1) has the same effect as that of lotensin.
      Therefore, in this study we assessed the effects of Lotensin or Salviae on the
      chronic CsA-induced upregulation of TGF-beta(1), TR-1, and TR-2 in a rat model.
      MATERIALS AND METHODS: Sodium-depleted rats were administered CsA by gastric
      gavage and a new rat model of chronic CsA-induced nephropathy was established.
      Rats with chronic CsA-induced nephropathy were treated by lotensin or Salviae.
      The proteins of TGF-beta(1), TR-1, and TR-2, and the mRNA of TR-1 and TR-2 in the
      kidneys of CsA-treated rats, were measured by immunohistochemistry (IHC) and in
      situ hybridization (ISH). The results were investigated semiquantitatively by
      image analysis. RESULTS: Lotensin or Salviae individually attenuated CsA-induced
      nephropathy in the rat models, and downregulated the protein expressions of TGF
      beta(1), TR-1, and TR-2, and the mRNA transcripts of TR-1 and TR-2 in the rat
      model. CONCLUSION: Our studies show that treatment with lotensin or Salviae is
      useful in preventing chronic CsA-induced nephropothy.

PMID- 16980038
TI  - The C-terminal peptide of connective tissue growth factor blocks the full
      molecule binding to tubular epithelial cell.
AB  - OBJECTIVES: Interstitial fibrosis is a critical pathologic change in chronic
      allograft nephropathy. The cytokine connective tissue growth factor (CTGF, also
      CCN2) plays an important role in epithelial-mesenchymal transformation (EMT) of
      tubular epithelial cells to renal interstitial fibrosis. The hexadeca-peptide
      within the C-terminal of CTGF (named P2) contains the unique binding domain of
      CTGF to its potential receptor, integrin alphavbeta3. This study examined whether
      P2 bound preferentially to the receptor and served as an inhibitor of CTGF.
      METHODS: All studies used an established rat kidney tubular epithelial cell line
      NRK-52E. Chemically synthesized P2 was purified, and some of it labeled with
      FITC. The affinity of CTGF or P2 to NRK-52E cells was examined by a solid-phase
      cell adhesion assay. Competitive binding between P2 and CTGF to NRK-52E cells was
      examined with flow cytometric analysis. RESULTS: Both P2 and CTGF bound to the
      NRK-52E cells, mediating cell adhesion. When the cells were incubated in the
      mixture of P2 and CTGF, P2 bound to the cells preferentially. Furthermore, when
      cells were preincubated with excessive CTGF, it became difficult for subsequent
      P2 binding to occur. CONCLUSIONS: P2 and CTGF seemed to bind to cell membranes at
      the same binding domain. P2 competitively blocked CTGF binding, acting as a CTGF
      inhibitor.

PMID- 16980040
TI  - The effect of renal ischemia-reperfusion injury on expression of RAE-1 and H60 in
      mice kidney.
AB  - INTRODUCTION: NKG2D, an activating receptor, may trigger NK and CD8+ T cells.
      Ligands for NKG2D and major histocompability complex class I chain-related
      antigen (MIC) have been reported to be expressed in rejected human renal
      allografts. MIC-NKG2D engagement may induce natural killer (NK) cell activation
      providing T-cell costimulation. We hypothesized that this interaction between
      innate and adaptive immunity may occur during kidney ischemia-reperfusion injury
      (IRI). METHODS: Male C57BL/6 mice after right renal resection were subjected to
      35 minutes of left renal ischemia: the ischemic group. Sham-operated mice
      underwent the same protocol without vascular occlusion. The sham and ischemic
      kidneys were removed at 2 to 7, 10, 14, or 28 days postoperatively. The normal,
      sham, and ischemic kidney tissues were collected for reverse-transcriptase
      polymerase chain reaction, and immunohistochemistry analysis of MIC homologues in
      mice (Rae-1 and H60). RESULTS: Compared with no expression in sham control and
      normal kidneys, IRI caused mRNA expression of Rae-1 from 2 to 10 days
      postoperatively and protein expression of Rae-1 from 2 to 14 days postoperatively
      in ischemic kidneys. We observed no expression of H60 mRNA or protein in any
      kidney. CONCLUSION: H60 transcripts have been reported to be present in the
      BALB/c background but not in C57BL/6. We found IRI did not cause H60 mRNA on
      protein expression in C57BL/6 kidneys. Rae-1 was absent in normal C57BL/6
      kidneys. The IRI-induced expression of the NKG2D ligand, Rae-1, might activate NK
      and CD8+ T cells. Our results suggested that MIC may be an important link between
      innate and adaptive immunity in kidney IRI.

PMID- 16980039
TI  - Polyphenol (-)-epigallocatechin gallate protection from ischemia/reperfusion
      induced renal injury in normotensive and hypertensive rats.
AB  - INTRODUCTION: The effect of epigallocatechin gallate (EGCG) in an in vivo renal
      model of ischemia with reperfusion (I/R) was compared between normotensive (WKR)
      and hypertensive (SHR) rats. METHODS: WKR (groups I, II, III) and SHR groups
      (groups IV, V, VI) were divided into three types. Groups I and IV were sham
      operated animals; groups II and V were subjected to 45 minutes of renal I/R; and
      groups III and VI received 10 mg/kg EGCG intravenously at the time of
      reperfusion. Three days after renal I/R, we compared renal function markers,
      malondialdehyde (MDA), and histologic changes. RESULTS: Following renal I/R,
      levels of blood urea nitrogen (BUN) and serum creatinine (sCr) were increased and
      serum creatinine clearance (CrCl) decreased in group V compared to group II (P <
      .001). Those receiving EGCG treatment (groups III and VI) had decreased BUN and
      sCr compared to non-EGCG I/R groups (P < .001), but not surprisingly, higher than
      sham groups. CrCl was lowest in the SHR groups. The MDA was significantly
      decreased after EGCG treatment (P = .028 in group III, P = .002 in group VI).
      Following renal I/R, tissue necrosis was more severe among SHR (P < .001).
      However, the ratio of regeneration to damage significantly increased in SHR after
      EGCG treatment. CONCLUSIONS: The reperfusion injury was greater among SHR
      compared with WKR in terms of renal function, lipid peroxidation, and tissue
      damage. EGCG treatment significantly ameliorated renal impairment and promoted
      tissue regeneration following renal I/R.

PMID- 16980041
TI  - Treatment with edaravone improves the survival rate in renal warm ischemia
      reperfusion injury using rat model.
AB  - Renal ischemia-reperfusion (I/R) injury during renal transplantation is a
      significant cause of renal dysfunction. The pathological role of free radicals in
      this process is a major concern. We investigated the effect of a free radical
      scavenger, edaravone (MCI-186), in renal I/R injury. Male Lewis rats (270 to 320
      g) were used for the model. The right kidney was harvested and left renal artery
      and vein were clamped as laparotomy. The kidney was reperfused after 90 minutes
      of ischemia. Edaravone (10 mg/kg) was delivered intravenously before ischemia and
      after reperfusion to prevent the neutrophil activation. In the nontreatment I/R
      group, no rat survived beyond 4 days. However, in the edaravone I/R treatment
      group, one among five rats survived more than 7 days. These results suggested
      that treatment with edaravone ameliorated renal I/R injury, and that the agent
      has the potential to ameliorate preservation injury in renal transplantation.

PMID- 16980042
TI  - Benefical effect of neutrophil elastase inhibitor on renal warm ischemia
      reperfusion injury in the rat.
AB  - Renal ischemia-reperfusion (I/R) injury is a significant problem in renal
      transplantation. Neutrophils play an important role in renal I/R injury. Several
      reports have demonstrated that neutrophil elastase derived from the activated
      neutrophils might play an important role in this injury. We investigated the
      effect of a neutrophil elastase inhibitor in renal I/R injury. Male Lewis rats
      (270-320 g) were used in the model. The right kidney was harvested and the left
      renal artery and vein were clamped at laparotomy. The kidney was reperfused after
      90 minutes of ischemia. Neutrophil elastase inhibitor (ONO-5046: 30 mg/kg) was
      delivered intravenously before ischemia and after reperfusion to prevent
      neutrophil activation. In the nontreatment I/R group, no hosts survived 4 days.
      However, after treatment with neutrophil elastase inhibitor, 3 of 10 rats in the
      I/R group, survived more than 7 days. These results demonstrated that treatment
      with neutrophil elastase inhibitor ameliorated renal I/R injury.

PMID- 16980043
TI  - Reperfusion liver injury induces down-regulation of eNOS and up-regulation of
      iNOS in lung tissues.
AB  - OBJECTIVES: Acute lung injury and inflammation can occur after hepatic
      ischemia/reperfusion (I/R). Little is known regarding the possible role of nitric
      oxide synthase expression in this complex type of lung injury. METHODS: Real-time
      polymerase chain reactions and immunohistochemistry were used to assess the mRNA
      and protein expression of eNOS and iNOS in lung tissue after I/R challenge to the
      liver. Ischemia was induced by clamping the hepatic artery and portal vein for 40
      minutes. After flow was restored, the liver was reperfused for 300 minutes. Blood
      samples were collected to assay three inflammatory parameters: tumor necrosis
      factor (TNF)-alpha, hydroxyl radicals, and NO. Lung lavage samples were assayed
      for protein and myeloperoxidase. The expression of eNOS and iNOS in lung tissues
      (n = 3) was also evaluated after I/R challenge to the liver. The iNOS inhibitor
      aminoguanidine was also tested in this I/R model. RESULTS: Reperfusion of the
      liver produced increased blood concentrations of TNF, hydroxyl radicals, and NO
      (P < .001; n = 8). Bronchial lavage fluids showed higher levels of protein and
      myeloperoxidase in the I/R than in the sham-treated group (P < .01). eNOS
      expression was down-regulated and iNOS expression up-regulated in I/R lung
      tissues (n = 3). The iNOS inhibitor aminoguanidine (10 mg/kg) significantly
      attenuated the lung injury. CONCLUSIONS: I/R injury to the liver induced lung
      injury involving systemic inflammatory responses and iNOS expression.
      Administration of aminoguanidine significantly attenuated the injury, suggesting
      that iNOS expression may play a critical role in lung injury induced by I/R of
      the liver.

PMID- 16980044
TI  - Hypoxia/reoxygenation up-regulated the expression of death receptor 5 and
      enhanced apoptosis in human hepatocyte line.
AB  - OBJECTIVES: Ischemia-reperfusion injury (IRI) is a key factor that contributes to
      early and late dysfunction of liver graft. Although we have known that
      hepatocytes express death receptors for tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL), the effects of TRAIL on hypoxia/reoxygenation (H/R)
      mediated apoptosis are unclear. This study sought to examine the effects of H/R
      on TRAIL cytotoxicity, as a cause of primary hepatic graft dysfunction, delayed
      graft refunction, and chronic graft dysfunction. METHODS: Using an hepatocyte H/R
      model in vitro to mimic IRI in the grafted liver, normal human hepatocytes HL
      7702 were exposed to hypoxia for 5 hours then reoxygenated for 0, 2, 4, 6, or 20
      hours. In another experiment, hepatocytes were exposed to hypoxia for 0, 2, 4, 8,
      or 20 hours. Expressions of TRAIL-R2/Death receptor 5 (DR5) mRNA were measured by
      semiquantitative reverse-transcriptase polymerase chain reactions. After 16 hours
      of hypoxia, human hepatocytes were treated with TRAIL in different concentrations
      for 5 hours. The death of hepatocytes was confirmed by flow cytometer and methyl
      thiazolyl tetrazolium analysis. RESULT: After 5-hour hypoxia, the expressions of
      DR5 mRNA increased at all times of reoxygenation. DR5 mRNA was up-regulated from
      0 hour after reoxygenation, reaching a peak value at 2 hours after reoxygenation
      compared with the normoxia cultured cells. Moreover, DR5 mRNA was up-regulated
      gradually following prolonged hypoxia. TRAIL-mediated cell killing was
      concentration-dependent being greater in the hypoxia treatment group compared to
      the normoxia group. CONCLUSIONS: H/R up-regulated the expression of DR5 and
      enhanced TRAIL-mediated apoptosis in an human hepatocyte line. The TRAIL pathway
      might play a critical role in hepatocyte apoptosis induced by IRI.

PMID- 16980045
TI  - Yisheng injection decreases the expression of H60 and RAE-1 genes in ischemic
      mice liver.
AB  - OBJECTIVE: Major histocompatability complex class I chain-related antigen A, B
      (MICA, B) functions as ligands for human NKG2D receptors, which may play a role
      in graft rejection and cellular stress. In this study we explored the effect of
      ischemia/reperfusion injury (IRI) on the expression of H60 and RAE-1 (MICA, B
      homologues) in mice to study the protective effect of Yisheng injection (YS), an
      herbal preparation developed from traditional Chinese medicine. METHODS: Male
      BALB/c mice were divided into sham, ischemic, and YS-treated groups using 90
      minutes of left liver lobe ischemia. Sham control mice underwent the same
      operation, but without vascular occlusion. In the treated group, YS (20 mg/kg)
      was given before ischemia and after reperfusion for 7 days. Liver samples
      collected at 7 days postoperation were used for real-time quantitative polymerase
      chain reaction analysis, Western blotting, and immunohistochemical assays.
      RESULTS: Compared with the sham group, H60 and RAE-1 mRNA levels were increased
      by sevenfold and 4.5-fold in the ischemic group, respectively. After YS
      treatment, they were reduced by 76% and 70%, respectively. Western blotting and
      immunohistochemical assays showed that there was absent or faint H60 and RAE-1
      expression in sham liver, but they were apparently increased in ischemic liver;
      however, the expressions were significantly decreased in the presence of YS.
      CONCLUSIONS: Hepatic IRI significantly increased H60 and RAE-1 expression in
      mouse liver. YS treatment effectively reduced this increase, seeming to attenuate
      NKG2D-ligand-mediated immune responses caused by IRI. This may suggest a new
      concept to prevent IRI and graft rejection.

PMID- 16980046
TI  - Total antioxidant status and oxygen free radicals during hepatic regeneration.
AB  - OBJECTIVES: The damage induced by oxygen free radicals (OFRs) is caused by an
      imbalance of the production of versus the antioxidant defenses against OFRs.
      METHODS: To understand hepatic damage induced by oxygen free radicals after
      hepatectomy in rats, total antioxidant status and total production of oxygen free
      radicals were serially measured in regeneration liver. At 1, 2, 3, 7, and 10 days
      after hepatectomy of Sprague-Dawley rats, blood was obtained into a capillary
      tube from a tail vein. Total antioxidant status and total production of oxygen
      free radicals were measured using the Randox kit, a colorimetric method, and the
      Free Radical Analytical System. We also measured the amount of malonyldialdehyde,
      which provides an indirect index of oxidative injury. RESULTS: The level of
      malonyldialdehyde after hepatectomy was higher compared with that before
      hepatectomy. The level of total oxygen free radicals after hepatectomy was higher
      compared with that before hepatectomy. Total antioxidant status after hepatectomy
      was lower compared with that before hepatectomy. CONCLUSIONS: The results
      suggested that the damage by OFRs to the regenerating liver was caused by
      increased production of OFRs and decreased antioxidant defense against OFRs.

PMID- 16980047
TI  - Ischemia/reperfusion-induced low reactivity of the rat superior mesenteric
      vascular bed is associated with expression of nitric oxide synthases.
AB  - Our objective was to investigate the mRNA and protein expressions of eNOS and
      iNOS in the mesenteric vascular bed after ischemia and reperfusion of the rat
      superior mesenteric artery (SMA) and the role of nitric oxide (NO) in the
      response of the vascular bed to vasoconstrictors following reperfusion of the
      SMA. METHODS: Real-time polymerase chain reaction and immunohistochemistry were
      used to monitor the mRNA and protein expression of eNOS and iNOS after I/R
      challenge to the rat SMA. Ischemia was induced by clamping the SMA for 40
      minutes, after which the flow was restored and the vessels were reperfused for
      300 minutes. Blood samples were collected for assays of lactic dehydrogenase,
      tumor necrosis factor (TNF), hydroxyl radical, and NO. After
      ischemia/reperfusion, the vascular beds were separated for analysis of the
      expression of eNOS and iNOS. The SMA with its associated intestinal tissue was
      isolated and perfused in vitro with Tyrode's solution (N = 8) then challenged
      with phenylephrine. RESULTS: Reperfusion of the SMA induced an increase in blood
      concentrations of lactic dehydrogenase (P < .001; N = 8), hydroxyl radical (P <
      .05), TNF (P < .001), and NO (P < .05). ENOS and iNOS mRNA expression increased
      1.3 +/- 0.1-fold and 19.6 +/- 3.5-fold, respectively when compared to the sham
      operated group. Protein expression increased 1.9 +/- 0.4-fold and 12.6 +/- 3.1
      fold, respectively, after reperfusion (N = 3) when compared with sham-treated
      rats. In vitro challenge showed that administration of phenylephrine (10(-8)
      approximately 10(-4) nmol) produced vasoconstriction in a dose-related manner.
      Maximum contractile responses to phenylephrine were attenuated in reperfused SMA.
      Addition of the NOS inhibitor N(G)-nitro-L-arginine (L-NNA, 10(-4) M) resulted in
      full recovery of the response to phenylephrine. CONCLUSIONS: Ischemia/reperfusion
      of the SMA results in a decrease in vascular reactivity of the mesenteric vessels
      that is dependent on NOS expression by the intestinal vascular bed.

PMID- 16980048
TI  - Lack of a protective effect of insulin on three reperfusion-liver injury models
      in rats and mice.
AB  - Our objective was to investigate the potential protective effects of insulin on
      the liver injury induced in three ischemia and reperfusion (I/R) models. METHODS:
      Three I/R models were used: (1) I/R of the liver was produced in isolated,
      perfused rat livers; (2) in in situ I/R of the liver in rats, ischemia was
      induced by clamping off the hepatic artery and portal vein for 40 minutes, the
      flow then restored, and the liver reperfused for 90 minutes; (3) in in situ I/R
      of the liver in mice, ischemia was induced by clamping off the hepatic artery for
      15 minutes, the flow then restored, and the liver reperfused for 45 minutes. In
      all three cases, blood samples collected before ischemia and after reperfusion
      were analyzed for sGOT. Plasma nitrate/nitrite, hydroxyl radicals, and tumor
      necrosis factor were also measured. In each model, a dose of insulin sufficient
      to induce euglycemia was administered to assess its protective effect on liver
      injury and inflammation. RESULTS: These I/R protocols resulted in a significant
      increase in sGOT and in three inflammatory parameters; nitric oxide, hydroxyl
      radicals, and tumor necrosis factor. Pretreatment with insulin did not attenuate
      the liver injury in any of the three I/R models. CONCLUSIONS: Although insulin
      has been reported to provide anti-inflammatory benefits by reducing oxidative and
      nitrosative stress and cytokine release, none of these protective effects was
      seen in the three I/R-induced liver injury models we tested.

PMID- 16980049
TI  - The possible study of HuaXi-1 solution for all intra-abdominal organ
      preservation: a study in rats.
AB  - OBJECTIVE: University of Wisconsin (UW) solution continues to be the most
      commonly used solution for intra-abdominal organs. However, it is expensive.
      Therefore, we have formulated HuaXi-1 (HX-1) solution. The aim of this research
      was to assess the effect of HX-1 solution compared to UW, Collins 2, and
      hypertonic citrate solutions on intra-abdominal organs. METHODS: The effects of
      HX-1 solution for all intra-abdominal organ preservation were studied in a
      noncirculated, isolated, perfused rat liver model, in rat pancreas isografts in
      diabetic rats, and in a kidney autotransplant model. The effects were
      investigated by measuring hepatic tissue water content, sinusoidal lining cell
      mortality, Krebs-Henseleits perfusate, aspartate aminotransferase, the number of
      livers secreting bile during isolated perfusion, blood glucose, glucose tolerance
      tests, serum insulin of the rat pancreas-transplant recipients, the maximum serum
      creatinine levels, kidney graft survival rates, and observing the morphological
      changes in liver, pancreas, and kidneys. RESULTS: HX-1 solution preserved rat
      liver well for 24 hours as effectively as UW, rat pancreas as well for 48 hours,
      and dog kidney as well for 72 hours. CONCLUSION: The experimental findings
      indicated that HX-1 solution was effective to preserve all intra-abdominal
      organs; it may simplify cold storage of organs for transplantation.

PMID- 16980050
TI  - Effect of cyclosporine on expression of MIC in human hepatocytes.
AB  - OBJECTIVES: The human major histocompatibility complex class I chain-related
      antigen A, B (MICA, B) are believed to be "cell stress sensors," which encode
      stress-inducible surface proteins that bind to NKG2D, an activating receptor of
      NK, alpha beta and gamma delta T cells. While cyclosporine (CsA) has improved
      patient and graft survival rates following solid organ transplantation, its
      clinical use is often limited by acute and chronic toxicity. Besides ischemia
      reperfusion injury, which could up-regulate the expression of MIC, the toxicity
      of CsA may also be another violent stress factor. The purpose of this study was
      to investigate whether CsA can affect the expression of MIC. METHODS: Various
      doses of CsA (5 or 20 microg/mL) was added to cultured human hepatocytes for 1,
      3, 5, 8, or 24 hours. The expression of MIC was measured by immunofluorescence
      using a laser scanning confocal microscope. RESULTS: CsA (5 or 20 microg/mL)
      upregulated MIC protein expression in hepatocytes at 1 hour, peaking at 3 hours,
      and persisting until 5 hours (P < .05), returning to normal levels after 8 to 24
      hours (P > .05). CONCLUSION: This study reported that CsA up-regulated MIC
      expression on human hepatocytes. MIC, as a "cellular stress biomarker," may play
      a significant role in activating NK, T, and B lymphocyte responses associated
      with transplantation. This study suggested that immunosuppressants produce
      deterioration in organ function in transplantation.

PMID- 16980051
TI  - Comparison of cyclosporine versus mycophenolate mofetil on expression of
      Fractalkine and CX3CR1 in chronic allograft nephropathy.
AB  - INTRODUCTION: We sought to investigate whether there was a difference between
      cyclosporine (CsA) and mycophenolate mofetil (MMF) to affect the expression of
      Fractalkine/CX3CR1 in chronic allograft nephropathy (CAN). METHODS: The Sprague
      Dawley Wistar rat accelerated kidney sclerosis model was performed as modified
      from the procedure of Kamada. Recipients were divided into three oral treatment
      groups (each group n = 8): group A was CsA 10 mg/kg . d for 10 days followed by
      vehicle; group B was CsA 10 mg/kg . d for 10 days followed by CsA 6 mg/kg.d;
      group C was CsA 10 mg/kg . d for 10 days followed by MMF 20 mg/kg . d.
      Pathological changes graded according to Banff 97 Standards were observed at 4,
      8, and 12 weeks posttransplantation. The immunohistochemistry and quantitative
      real-time fluorescence polymerase chain reaction (PCR) were used to assess the
      distribution and expression of Fractalkine/CX3CR1 in the grafted kidney. RESULTS:
      Fractalkine/CX3CR1 were mostly expressed in the tubulointerstitium and tubular
      epithelial cell basolateral membrane. A proportion of the vessel showed positive
      staining for Fractalkine/CX3CR1, occasionally in glomerular parietal wall cells.
      The expression of Fractalkine/CX3CR1 in grafted kidneys at all the time points
      was significantly less in the MMF than in the CsA group or the control group (P <
      .05). Real-time fluorescence quantitative PCR revealed similar outcomes as
      immunohistochemistry. The expression of Fractalkine coincided with CX3CR1.
      CONCLUSION: Fractalkine/CX3CR1 may play an important role in the development of
      interstitial fibrosis in CAN. Different immunosuppressants have various effects
      on expression of the Fractalkine/CX3CR1.

PMID- 16980052
TI  - Cyclosporine-induced apoptosis in osteosarcoma cells.
AB  - INTRODUCTION: Posttransplant bone disease is one of the complications of
      cyclosporine (CsA), which is widely used as an immunosuppressive agent in the
      field of kidney transplantation. Cyclosporine treatment causes osteopenia as a
      result of altered bone turnover, but the pathogenic mechanisms of this process
      remain unclear. This study examined the ability of CsA to induce apoptosis in a
      rat osteoblast cell line. RESULTS: We induced apoptosis in rat osteoblastic ROS
      17/2.8 cells by exposure to CsA. MTT assay showed that CsA exhibited significant
      cytotoxic effects on ROS 17/2.8 cells in a dose-dependent manner. Western blot
      analysis showed enhanced processing of caspase-8, Bax, and p53 after CsA
      treatment. Expression of cleaved poly (ADP-ribose) polymerase (PARP) was elevated
      by CsA treatment. Pro-caspase-3 and Bcl-2 proteins were decreased by CsA.
      CONCLUSIONS: These results suggested that CsA induced apoptosis of osteoblasts.

PMID- 16980053
TI  - Effects of cyclosporine and tacrolimus on the oxidative stress in cultured
      mesangial cells.
AB  - OBJECTIVES: Cyclosporine (CsA) and tacrolimus (Tac) are two primary
      immunosuppressive agents used for the prevention of graft rejection. However,
      their use is associated with significant side effects, most notably
      nephrotoxicity. The mechanisms of this toxicity are not fully understood, but
      they seem to be associated with increases in the production of oxygen free
      radicals (OFRs). This present work examined the effect of CsA and Tac on the
      production of OFRs in cultured rat renal mesangial cells (RMCs). METHODS: Varying
      concentrations of CsA and Tac (0 to 40 micromol/L) were added to RMCs and
      incubated for 60 minutes at 37 degrees C. The production of OFRs was evaluated by
      measuring the fluorescent product from the oxidation of an oxidant-sensitive 2',
      7'-dichlorofluorescin. RESULTS: At 60 minutes, the relative fluorescence units
      (RFU) for OFRs production in RMCs exposure to CsA were increased by 2.5%, 11.5%,
      22.5%, 57.2%, and 174% at 2.5, 5, 10, 20, and 40 micromol/L, respectively. Tac
      increased the RFU by 15.9%, 13.6%, 14.8%, 13.2%, 21.4%, 13.2%, and 28.1% at 0.1,
      1, 2.5, 5, 10, 20, and 40 micromol/L, respectively. In RMCs, the RFU produced by
      CsA was higher than that by Tac. CONCLUSIONS: The results of this experiment
      suggest that CsA and Tac induced renal injury by OFRs.

PMID- 16980054
TI  - Effect of tacrolimus on the production of oxygen free radicals in hepatic
      mitochondria.
AB  - OBJECTIVES: Cyclosporine (CsA) causes side effects that occur mainly in the
      kidney but also in the liver. Several reports have strongly suggested that the
      production of oxygen free radicals (OFRs) is a common mechanism of CsA toxicity.
      However, tacrolimus is believed to suppress the production of OFRs. METHODS: We
      obtained the mitochondrial fraction with 96% purity from rat liver using a
      sucrose density gradient solution. Zero to 100 micromol/L tacrolimus was
      incubated with the mitochondrial fraction for 6 hours at 37 degrees C. OFRs were
      evaluated by measuring the fluorescent product from the oxidation of an oxidant
      sensitive 2,7-dichlorefluorescein using a VICTOR3 multilabel counter. RESULTS:
      The fluorescence units for OFR production were increased as the time of exposure
      to tacrolimus passed from 1 to 6 hours. The fluorescence units in 0.1 micromol/L
      tacrolimus were 6.0 x 10(5) at 1 hour, 7.8 x 10(5) at 2 hours, 9.0 x 10(5) at 3
      hours, 10.0 x 10(5) at 4 hours, 11.1 x 10(5) at 5 hours, and 11.4 x 10(5) at 6
      hours. However, the fluorescence units were similar although the tacrolimus
      concentration increases from 0.1 to 100 micromol/L. CONCLUSIONS: The results in
      this experiment suggested that tacrolimus induced the production of OFRs
      depending on the exposure time.

PMID- 16980055
TI  - Apoptosis by cyclosporine in mesangial cells.
AB  - INTRODUCTION: The immunosuppressive agent cyclosporine (CsA) is widely used to
      treat allograft rejection and various autoimmune disorders. A major limiting
      factor in the use of CsA is chronic nephrotoxicity. The pathogenesis of CsA
      induced nephrotoxicity is not fully understood. Several recent studies have
      suggested that CsA treatment directly induces apoptosis in several cell types.
      The present study was undertaken to investigate the effects of CsA on apoptosis
      of cultured rat mesangial cells (RMCs). METHODS: RMCs were treated with CsA at
      concentrations of 0.1 to 40 mumol/L. Cell viability was determined by MTT assay.
      Apoptotic protein expression was determined by Western blot analysis. RESULTS:
      Cell viability was decreased with increasing concentrations of CsA in dose
      dependent manner. CsA produced dose-dependent induction of p53, caspase-6, and
      Bax protein expression. CsA treatment caused proteolytic cleavage of caspase-3
      and induced the degradation of 116-kDa PARP into 89-kDa fragment. RMCs with CsA
      reduced Bcl-2 and cIAP expression. CONCLUSIONS: In this study, CsA induced
      apoptosis by up-regulating proapoptotic factors, caspase-3 and -6, p53, Bax,
      cleaving PARP, and down-regulating antiapoptotic factor, Bcl-2, and cIAP. These
      results suggested that the increased cell apoptosis exerted by CsA may be one of
      the mechanisms promoting CsA-induced nephrotoxicity.

PMID- 16980056
TI  - Distribution of the alpha-gal epitope on adult porcine bone tissue.
AB  - INTRODUCTION: Bone xenografts from pig to human appear to be an alternative to
      resolve the shortage of bone autologous and allografts. However, the major
      obstacle of pig-to-human xenotransplantation is the interaction between human
      natural anti-Gal antibody and the alpha-Gal epitope abundantly expressed on pig
      endothelium. It was important to investigate the expression of alpha-Gal epitopes
      in porcine bone tissue to look for an ideal method to remove the alpha-Gal
      epitopes. METHODS: The cortical and trabecular bone were retrieved from five
      pigs. After the soft tissues and periosteum were removed, the blood and marrow
      cavity were cleaned with phosphate-buffered solution. All 5 mm x 5 mm x 5 mm
      samples were imbedded in paraffin and methyl methacrylate resin for histological
      sections. The mouse IgM M86 monoclonal antibody, which was highly specific for
      alpha-Gal epitopes, was used to document alpha-Gal epitope expression by
      immunostaining of tissues and immunofluorescence. RESULTS: Gal-positive
      immunostaining and immunofluorescence were observed on the surface of osteocytes
      and Haversian canals. There was a significant difference in Gal expression
      between cortical and trabecular bone tissues. There was no Gal expression in the
      extracellular matrix of bone. CONCLUSIONS: Major alpha-Gal epitopes were on the
      surface of osteocytes of porcine bone tissues. A method should be used to damage
      the osteocytes and eliminate the alpha-Gal epitopes to avoid the xenogenic
      rejection in xenotransplantation of porcine bone tissues.

PMID- 16980057
TI  - Phylogenetic analysis of porcine endogenous retroviruses expressed in Chinese
      pigs based on envelope sequences.
AB  - The promise of successful clinical xenotransplantation is now offset by the
      potential risk of transmission of porcine endogenous retrovirus (PERV). PERV
      consists of three subtypes according to the varieties of env sequences. We
      analyzed PERV subtypes in two species of Chinese pigs (Banna minipig inbred, BMI,
      and Wu-Zhi-Shan pig, WZSP). Positive A and B were detected while positive C was
      absent in the analyzed Chinese pigs. The polymerase chain reaction products were
      then cloned into a pGEM-T vector system and sequenced. Phylogenetic trees were
      constructed from the translated amino acids of PERVs and other type C and type D
      retrovirus, as well as the lentivirus in the GeneBank. The results suggested that
      PERV-A and PERV-B that exist in Chinese pig genomes share similarities with other
      PERV from the GeneBank and some type C retroviruses, including lymphotropic,
      leukemic and endogenous retroviruses.

PMID- 16980058
TI  - The lack of inhibition of porcine endogenous retrovirus by small interference RNA
      designed from the long terminal regions.
AB  - Xenotransplantation from pigs may offer a potential solution to the organ
      shortage. However, there remains the risk of xenoinfection by porcine endogenous
      retroviruses (PERVs) that cannot be eliminated by breeding pigs under specified
      pathogen-free conditions. RNA interference is a new method to inhibit the
      expression of a specific gene. Here, we designed two siRNAs from the long
      terminal repeat of PERV. Our results showed that these siRNAs had no inhibitory
      effects. The possible reasons for this are an off-target effect or a problem with
      specific sequence of RNAi. Future work should focus on siRNAs from conserved
      regions of other PERV genes.

PMID- 16980059
TI  - In vivo screening of porcine endogenous retrovirus in Chinese Banna minipig
      inbred.
AB  - The risk of porcine endogenous retrovirus (PERV) infection is one of the major
      barriers in clinical trials of pig-to-human xenotransplantation. Previous
      experiments showed that PERV could infect many types of human and nonhuman
      primate cells, but there is no reported evidence of in vivo infection. In this
      study, extracted genomic DNA from tissues of seventeen pigs was analyzed using
      specific sequence primers for gag, pol, and env. The results suggested that PERV
      exist in the genomes of all tissues. A subtype analysis indicated that PERV-A and
      PERV-B were in the tissue genome with no positive PERV-C. A greater understanding
      of the properties of PERV in different pig tissues is necessary to evaluate the
      risk posed by PERV.

PMID- 16980060
TI  - Construction and characterization of a cDNA library from liver tissue of Chinese
      Banna minipig inbred line.
AB  - A xenograft that performs efficient functions is an essential premise for
      successful xenotransplantation. Our early study indicated that Chinese Banna
      minipig inbred line (BMI) was an ideal xenograft donor. However, the activities
      of some proteins synthesized by the BMI liver are different from the human, which
      could lead to functional disorders in coagulation, fibrinolysis, and
      anticoagulation after liver xenotransplantation. Therefore, it is important to
      investigate the genetic background of protein incompatibility and to provide new
      strategies for gene manipulation. In this study we constructed a cDNA expression
      library using BMI liver tissue to obtain an understanding of nucleic acid and
      protein differences between the two species. We extracted total RNA and purified
      mRNA of the liver tissue from one of the sixteenth inbred generation of BMI/JS
      151 substrain. After double-strand cDNA synthesis, we fractionated it on a CHROMA
      APIN-400 column; ligated the longer than 500bp cDNA into a ZAP Express Vector;
      and performed a lambda: phage packaging reaction, library amplification, and
      titer. We randomly picked 12 plaques and tested the length of inserts. The titers
      of the primary and amplified libraries were 1.0 x 10(6) pfu/mL and 5.0 x 10(9)
      pfu/mL, respectively. The percentages of recombinants were 97.0% in the primary
      library and 98.0% in the amplified library. The lengths of most inserts were
      between 750 bp and 2.0 kb. Thus, we successfully constructed a cDNA expression
      library from BMI liver tissue. Using the library, we hope to get a full-length
      cDNA of some important genes and conduct further studies on porcine liver
      function in xenotransplantation.

PMID- 16980061
TI  - Immunogenicity and immune modulation of osteogenic differentiated mesenchymal
      stem cells from Banna minipig inbred line.
AB  - Mesenchymal stem cells (MSCs) represent a good choice for cell transplantation
      due to their multilineage differentiation ability and low immunogenicity. Our
      previous in vitro studies indicated that undifferentiated swine MSCs show low
      immunogenicity suppressing the proliferative responses of human peripheral blood
      lymphocyte to several antigens. In this study, we investigated the immunogenicity
      and immune modulation ability of osteogenic differentiated MSCs. SLA class I (P1,
      P14) was detectable by reverse-transcriptase polymerase chain reaction on both
      differentiated and undifferentiated MSCs. SLA class II (SLA-DRA, SLA-DQA) was
      only detectable on differentiated MSCs mixed lymphocyte reaction assays
      demonstrated that both differentiated and undifferentiated MSCs failed to
      stimulate proliferative responses by human peripheral blood lymphocytes (hPBLs).
      Furthermore, as undifferentiated MSCs, osteogenic differentiated MSCs also
      suppressed hPBL proliferation to phytohemaglutinin.

PMID- 16980062
TI  - The hDAF exogene protects swine endothelial and peripheral blood mononuclear
      cells from xenoreactive antibody mediated cytotoxicity in hDAF transgenic pigs.
AB  - Xenoreactive antibody-induced complement activation and cytotoxicity poses a
      major obstracle to xenograft survival in humans. Previously, we have generated
      transgenic pigs carrying the hDAF exogene to help overcome this problem. In this
      study, we examined whether the hDAF exogene in various swine cells shows an
      equally protective effect for the complement-mediated cytotoxicity induced by
      human xenoreactive antibodies. Pig peripheral blood mononuclear cells (PBMCs) and
      aortic endothelial cells (PAECs) were used as targets. Fresh human serum was
      harvested from a single healthy human donor as the source of human xenoreactive
      antibodies and complement. The target cells cocultured with medium containing
      various concentrations of human serum for 24 hours were evaluated using the 3
      [4,5-dimethylthiaolyl]-2,5-diphenyl-tetrazolium bromide assay for cellular
      viability. We observed that xenoreactive antibody plus human complement-mediated
      cellular cytoxicity dose-dependently correlated with the concentration of human
      serum in the culture medium. As compared with the PBMCs from the normal pigs,
      PBMCs from hDAF transgenic pigs showed significantly better survival after
      treatment with human serum (P < .05). Similarly, the survival of PAECs from the
      hDAF transgenic pig were also significantly higher than that from normal pigs (P
      < .05). Our data demonstrated a protective effect from human xenoreactive
      antibodies and complement-mediated cytoxicity of hDAF exogenes in pig PBMCs and
      PAECs. These observations support the clinical value of the hDAF transgenic pig
      as an organ donor in xenotransplantation.

PMID- 16980064
TI  - Use of the SCOT solution in kidney transplantation: preliminary report.
AB  - SUBJECT: This article reports preliminary findings relating to the use of a new
      preservation solution, the Solution de Conservation des Organes et des Tissus
      (SCOT), in renal transplantation. This fourth-generation solution combines an
      extracellular-like composition with 20 kDa polyethylene-glycol, known for its
      cell-protection capacity and immunocamouflage properties. METHODS: We have
      reported preliminary data obtained in 29 transplantations (25 cadaveric donors
      and 4 living related donors) between December 2004 and November 2005. The SCOT
      solution was used for both in situ flush and static preservation. We compared
      primary organ nonfunction and delayed graft function rates as well as blood
      creatinine levels in recipients of grafts processed with SCOT solution, versus
      University of Wisconsin solution (paired for age with the previous group) and
      with EuroCollins solution (historic data). RESULTS: We observed delayed graft
      function in 10% of the SCOT-processed group, 14% in the University of Wisconsin
      solution group, and 23% of the EuroCollins group. No case of primary organ
      nonfunction was reported. Creatinine levels in both SCOT and University of
      Wisconsin solution groups were similar. We did not observe any humoral or
      cellular graft rejection in the first 3 months after transplantation. In light of
      these preliminary results, the use of SCOT is safe for kidney preservation in the
      human setting. Further experience is warranted to assess the clinical
      consequences of its immunocamouflage properties as described in animal models.

PMID- 16980065
TI  - A simple and reliable method to assess heart viability after hypothermic
      procurement.
AB  - Hearts from brain dead pigs (n = 18) were submitted to 0 (group I), 10 (group
      II), or 20 (group III) minutes of in situ warm ischemia (animal exsanguination).
      After harvesting, cold cardioplegia solution was perfused in retrograde fashion
      and initial coronary flow (ICF) measured. After left ventricular energetic
      indices were measured using NMR spectroscopy, the hearts were transplanted
      orthotopically. Follow-up was performed over 120 minutes after cardiopulmonary
      bypass. We observed a progressive decrease in ICF with increased warm ischemia
      times: 50 +/- 3.4 mL/min per 100 g of tissue in the group I, 36 +/- 7 and 30 +/-
      3.5 in groups II and III, respectively (P < .05 and P < .01 versus group I). The
      ICF strongly correlated with the energetic index (r = 0.76, P < .001) and with
      posttransplant function of the transplanted heart. These data showed that
      measurement of initial coronary flow after cardioplegia was a reliable test to
      evaluate cardiac graft viability before transplantation.

PMID- 16980066
TI  - High energy compound stability during experimental brain death.
AB  - The aim of this study was to examine the effect of sudden brain death (BD) on
      myocardial function and high energy phosphate (HEP) stores. BD was induced by
      cerebral vessel ligation in six swine (BD group) that were compared to six
      control swine. At the end of the BD period (3 hours), harvested hearts were
      stored at 4 degrees C. Myocardial tissue HEP were assessed by: (i) (31)P-NMR
      spectroscopy of left ventricle for phosphocreatine (PCr), adenosine triphosphate
      (ATP), inorganic phosphate (Pi) and intracellular pH (pHi), and by (ii) HPLC for
      ATP, ADP, and AMP levels in left ventricle biopsies. Brain death resulted in a
      instantaneous major increase in catecholamines (>50-fold, P < .001) and
      paradoxically a significant progressive decrease in the regional contractility of
      the left ventricle. After cardioplegia, no significant differences on HEP
      compounds (ATP/Pi, PCr/Pi, ATP, energetic index) or in pHi were observed between
      BD and control groups. These data suggest that early heart injury occurring
      during BD does not seem to be an ischemic phenomenon.

PMID- 16980067
TI  - Estimation of the glomerular filtration rate through different methods in kidney
      transplant recipients: correlation with the creatinine clearance measurement.
AB  - The measurement of the glomerular filtration rate (GFR) is an important tool for
      physicians to follow kidney transplant recipients. Indeed, renal function has
      been shown to be predictive of graft outcome in retrospective studies. Several
      methods have been proposed to measure GFR. In the present study we evaluated the
      correlation of GFR between a reference method (calculation through the urine to
      plasma ratio of creatinine [UV/P] formula) and three estimation equations
      (Cockcroft and Gault; Nankivell; modification of diet in renal disease) in 81
      kidney transplant recipients at 3 and 12 months posttransplantation. We showed a
      significant correlation between the three predictive formulas and UV/P, but none
      of the predictive equations showed an excellent correlation. The best correlation
      between an estimation equation and the UV/P formula was the CG formula. Further
      studies are required to compare the estimated GFR with better reference methods,
      such as the use of isotopic markers in kidney graft recipients.

PMID- 16980068
TI  - Effect of mycophenolate mofetil monotherapy on T-cell functions and inosine
      monophosphate dehydrogenase activity in patients undergoing a kidney
      transplantation.
AB  - The aim of this study was to assess the effects of 1 g of mycophenolate mofetil
      (MMF) on T-cell function and inosine monophosphate dehydrogenase (IMPDH) activity
      among patients undergoing kidney transplantation. Five patients undergoing renal
      transplantation from a living donor were enrolled in this study. Compared to
      baseline (before MMF intake), CD25 and CD71 expression were significantly
      decreased during the first hour following MMF intake. T-cell proliferation and
      IMPDH activity also decreased dramatically. Thereafter, all biomarker levels
      increased over time. At 4 hours, CD25 and CD71 levels, as well as IMPDH activity,
      returned to almost baseline values, whereas T-cell proliferation remained below
      baseline. Intracytoplasmic IL-2 expression remained unchanged after MMF
      ingestions. In conclusion, administration of 1 g of MMF was associated with a
      transient decrease in CD25 expression in addition to a temporary dramatic
      decrease in both T-cell proliferation and IMPDH activity.

PMID- 16980069
TI  - New onset diabetes mellitus incidence and risk factors in kidney transplantation:
      results of the observational cross-sectional study diapason.
AB  - BACKGROUND: New-onset diabetes mellitus (NODM) is a frequent complication of
      kidney transplantation. Data on NODM are mainly available in the United States. A
      study was implemented in a French population of kidney transplants. The incidence
      and risk factors of NODM were analysed. Diabetes was defined according to
      American Diabetes/World Health Organization guidelines. METHODS: Diapason is an
      observational cross-sectional study of 527 kidney transplant patients from 17
      units based on data collected at a single routine visit 6 to 24 months after
      kidney transplantation. RESULTS: The mean age of the patients was 47.2 years, and
      61.1% were men; 49.5% were receiving cyclosporine microemulsion and 50.5%
      tacrolimus. NODM developed in 7.0% after a median interval of 1.6 months.
      Univariate analysis identified six pretransplantation risk factors: advanced age,
      impaired fasting glucose, at least two cardiovascular risk factors, hepatitis C
      status, maximums lifetime body mass index above 25, and tacrolimus or
      cyclosporine therapy. Four independent factors were identified by multivariate
      analysis: body mass index above 25 (OR = 5.1), pretransplantation impaired
      fasting glucose (OR = 4.7), hepatitis C status (OR = 4.7), and tacrolimus versus
      cyclosporine treatment (OR = 3.0). CONCLUSIONS: NODM is associated with risk
      factors present prior to kidney transplantation and with treatment with
      tacrolimus as opposed to cyclosporine. Therefore, the choice of calcineurin
      inhibitor should be based on the patient's overall risk profile.

PMID- 16980070
TI  - Long-term results of monoclonal anti-Il2-receptor antibody versus polyclonal
      antilymphocyte antibodies as induction therapy in renal transplantation.
AB  - We compared the influence of induction therapy on 5-year patient and graft
      survival as well as on renal function in 100 kidney graft recipients at low
      immunological risk treated with antilymphocyte globulin (n = 50) versus anti-IL
      2R monoclonal antibody (n = 50) in a prospective multicenter study. Long-term
      immunosuppressive treatment included cyclosporine, mycophenolate mofetil, and a
      short course of steroids in all patients. Five year graft (86% vs 86%) and
      patient (94% vs 94%) survivals were identical in both study arms. Moreover,
      neither serum creatinine or proteinuria were significantly different between the
      two groups. Our results showed that the choice of the induction therapy seemed to
      not have a major impact on long-term outcomes among renal recipients at low
      immunological risk.

PMID- 16980071
TI  - Plasma levels of soluble CD30 in kidney graft recipients as predictors of acute
      allograft rejection.
AB  - In renal transplant recipients elevated soluble serum CD30 levels are associated
      with increased rejection and graft loss. We sought to determine the sCD30 plasma
      levels before and after kidney transplantation and to assess whether sCD30 was a
      predictive factor of immunological risk. sCD30 plasma levels were determined by
      an enzyme-linked immunosorbent assay assay in 52 kidney graft recipients before
      as well as 7, 15, and 21 days after transplantation. Eighteen patients developed
      acute allograft rejection (group I) and 34 patients showed uneventful courses
      (group II). Before transplantation sCD30 plasma levels were elevated in both
      groups (mean: 162.6 +/- 89.5 U/mL). After transplantation, group I recipients
      with acute rejection showed higher relative levels of plasma sCD30 on days 7 and
      15 (120.8 +/- 74.6 U/mL and 210.6 +/- 108.7 U/mL respectively) compared with
      group II patients without rejection (95 +/- 45 U/mL and 59.4 +/- 31.6 U/mL), a
      difference that was significant for group I (P = .0003) and not significant for
      group II (P = .09). On day 21, sCD30 decreased in the two groups but remained
      higher among group I patients (120.6 +/- 92.7 U/mL). HLA antibodies were positive
      in 18 patients (34.6%) with 9 (50%) experiencing at last one episode of acute
      rejection. Among 34 patients negative for anti-HLA antibodies, nine displayed
      acute rejection only (26.4%), a difference that was not significant (P > .05). If
      we consider 100 U/mL as the minimum predictive level for allograft rejection, our
      results suggested that levels of sCD30 should be taken into consideration with
      the presence of HLA-antibodies detectable before and after transplantation,
      especially in patients with more than three HLA mismatches [RR = 3.20 (0.94 < RR
      < 10.91)]. These data suggested that measurement of plasma sCD30 is a useful
      procedure for the recognition of rejection in its earliest stages.

PMID- 16980072
TI  - Ctla-4 exon 1 (+49) and promoter (-318) gene polymorphisms in kidney
      transplantation.
AB  - To investigate the association between kidney transplant rejection and the
      polymorphisms of CTLA-4 gene exon 1(+49) and promoter (-318), genomic DNA of 70
      renal transplant recipients and 110 healthy blood donors were genotyped by PCR
      RFLP and PCR-SSP, respectively. The patients were classified in two groups: G1
      included 33 HLA-identical recipients and G2, 37 one haplo-identical recipients.
      Thirty-one recipients experienced an acute rejection episode: 10 in G1 and 21 in
      G2. Ten G2 patients developed chronic allograft dysfunction (CAD). Allelic
      frequencies and genotype distribution were similar among patients and controls.
      CTLA-4 exon 1 genotype A/A and CTLA-4 promoter genotype C/C were significantly
      higher among G2 patients with CAD than without CAD (P < .01). The distribution of
      CTLA-4 exon 1-promoter genes did not reach significance between graft recipients
      and controls. The genotype frequency of (G/G-C/C) was increased among controls
      (42.72%) compared with graft recipients (G1 and G2; 35.71%). CTLA-4 polymorphisms
      gene were associated with susceptibility to chronic allograft dysfunction.

PMID- 16980073
TI  - Anti-donor DR103 Immunization in a DRB1*0101 kidney allograft recipient.
AB  - Posttransplant appearance of donor-specific anti-HLA antibodies is correlated
      with poor graft survival. Herein, we have provided evidence that an HLA-DRB1*0101
      kidney allograft recipent developed anti-DR103 antibody after receiving a
      transplant from a HLA-DRB1*0103 cadaveric donor, resulting in graft loss. HLA
      DRB1*0103 is a rare allele in Caucasian populations. It differs from DRB1*0101
      only by three amino-acid substitutions and may play a central role in
      allorecognition. Nevertheless, our data showed that it induced alloimmunization
      in a DRB1*0101 recipient. Therefore, this new possibility of immunization must be
      taken into account before transplantation as well as after grafting.

PMID- 16980074
TI  - Rituximab therapy for mixed cryoglobulinemia in seven renal transplant patients.
AB  - Systemic B-cell depletion and clinical remission of the systemic effects of
      cryoglobulins have been achieved in hepatitis C virus-positive immunocompetent
      patients with rituximab, a human/mouse chimeric monoclonal antibody that
      specifically reacts with the CD20 antigen. Thus, this provides a rationale for
      the use of rituximab for type III cryoglobulin-related graft dysfunction in renal
      transplant patients. Seven patients, of whom five were hepatitis C positive,
      developed renal function impairment long after transplantation, as well as de
      novo nephrotic syndrome (n = 5), severe hypertension (n = 5), nephritic syndrome
      (n = 1), and increased serum creatinine (n = 1). This type III cryoglobulinemia
      was associated with membranoproliferative glomerulonephritis and with thrombi
      within the glomeruli in one case. In addition to their baseline standard
      immunosuppressive medications, the patients were given weekly rituximab
      infusions: 375 mg/m(2) for 2 weeks in four cases, for 3 weeks in one case, and
      for 4 weeks in two cases. This treatment resulted in a dramatic improvement in
      all renal parameters, particularly a sustained remission of nephrotic syndrome in
      three cases, the disappearance of nephritic syndrome in one patient, and improved
      nephrotic syndrome in two cases, as well as a sustained clearance of
      cryoglobulins in six cases. However, it also resulted in severe infectious
      complications in two cases. We concluded that rituximab therapy is effective in
      cryoglobulin-related renal dysfunction in renal transplant patients but, due to
      chronic immunosuppression, this may be achieved at the expense of infectious
      complications.

PMID- 16980075
TI  - New onset dyslipidemia after renal transplantation: is there a difference between
      tacrolimus and cyclosporine?
AB  - Lipid abnormalities including increased total cholesterol (TC), triglycerides
      (TG) and low density lipoprotein cholesterol (LDL-C) have been frequently
      reported in renal transplantation and could be involved in the high frequency of
      cardiovascular diseases in this population. PATIENTS AND METHODS: Two hundred
      ninety-five patients were transplanted between January 1995 and October 2000 in
      our center. Two hundred two patients were included in this study. Seventy-six
      patients received tacrolimus (Tac), and 126 patients cyclosporine (CsA). Lipid
      parameters were assessed the day of transplantation and 1 year
      posttransplantation. RESULTS: Serum lipids were similar between the two groups at
      D0. At M12, TC and LDL-C were significantly higher in the CsA group (6.14 +/-
      1.37 vs 5.28 +/- 1.32 mmol/L; P < .05 and 3.98 +/- 1.05 vs 3.26 +/- 1.03 mmol/L;
      P < .05 CsA vs Tac, respectively). TG were comparable in both groups (1.86 +/-
      1.07 vs 1.62 +/- 0.92 mmol/L; P = .55; CsA vs Tac). Incidence of de novo
      hypercholesterolemia was significantly higher in the CsA group (28 vs 8%) whereas
      incidence of hyperTG was similar in both groups. Prevalence of LDL-C was
      significantly higher in the CsA group (65% vs 31%; P < .001), whereas there was
      no difference in high density lipoprotein (HDL)-C levels. DISCUSSION: Mean serum
      lipid levels and incidence and prevalence of hyperTC, especially LDL-C, was
      significantly higher in patients receiving CsA when compared with Tac. TG and HDL
      C levels were similar. Although the study was retrospective, our results confirm
      that CsA increases lipid levels, whereas Tac does not. CONCLUSION: Lipid
      disorders are frequently observed in renal transplant recipients. CsA, but not
      Tac, significantly increases incidence and prevalence of high TC and LDL-C.

PMID- 16980076
TI  - Small dense low-density lipoprotein in renal transplant recipients: a potential
      target for prevention of cardiovascular complications?
AB  - BACKGROUND: Immunosuppressive therapy is frequently associated with dyslipidemia,
      which is involved in cardiovascular morbidity and mortality in transplant
      patients. Beyond classical factors, such as low-density lipoprotein (LDL)
      cholesterol (LDL-C), qualitative abnormalities of lipoproteins, such as presence
      of the atherogenic factor, small dense LDL, may be of interest for a
      cardiovascular risk assessment. This study was designed to explore LDL size in
      renal transplant recipients in relation to quantitative lipid parameters and
      apolipoprotein (apo) CIII polymorphism. METHODS: Total cholesterol (TC), high
      density lipoprotein cholesterol (HDL-C), LDL-C, apoA1, apoB, apoCIII, and LDL
      size were measured in 62 patients of mean age 45 +/- 13 years including 71% men
      at 2 +/- 0.5 years after renal transplantation. Thirty-two patients received
      cyclosporine (CsA), while 30 received tacrolimus (FK). ApoCIII Sstl genotype was
      determined by restriction fragment length polymorphism. RESULTS: The CsA group
      exhibited higher TC (P = .001), LDL-C (P = .004), non-HDL-C (P = .009), HDL-C (P
      = .03), apoB (P = .008), and apoCIII (P = .002) levels than the FK group.
      However, LDL-C (CsA: 3.7 +/- 1.2, FK: 3.0 +/- 0.6 mmol/L) and triglyceride levels
      (CsA: 1.55 mmol/L, FK: 1.37 mmol/L) were near the normal range in both groups.
      Allelic frequency of the sparse A2 allele associated with hypertriglyceridemia
      was 6%, similar to the general population. LDL size, which was comparable in the
      CsA and FK groups (25.87 +/- 0.89 vs 25.75 +/- 0.62 nm, respectively), inversely
      correlated with TG/HDL ratio (P = 10(-4)). Prevalence of small dense LDL (defined
      as <25.5 nm) was 26% in the CsA group and 33% in the FK group. CONCLUSION: After
      LDL-C goal has been achieved, LDL size modulation may be taken into account in
      order to prevent cardiovascular complications.

PMID- 16980077
TI  - Renal transplantation decreases osteoprotegerin levels.
AB  - Vascular calcifications are an important risk factor for cardiovascular mortality
      and morbidity in patients with chronic renal failure. Osteoprotegerin, a soluble
      decoy receptor for receptor activator NFkB ligand, has emerged as an independent
      predictive factor of atherosclerosis and vascular calcification in hemodialysis
      patients. Sparse data are available on the evolution of osteoprotegerin after
      renal transplantation. The aim of this study was to follow the evolution of serum
      osteoprotegerin levels and biochemical risk factors after renal transplantation.
      Forty patients were included. Blood samples for analysis were collected before
      and 3 months after renal transplantation. Besides the expected diminution in
      calcium-phosphate product, we have shown an early normalization of
      osteoprotegerin (10.05 +/- 4.77 pmol/L to 4.59 +/- 2.26 pmol/L). This study
      demonstrates that kidney transplantation improves this risk factor for vascular
      calcifications. However, these preliminary results should be confirmed and
      extended by the follow-up of vascular calcifications in the long term.

PMID- 16980078
TI  - Early proteinuria is a strong indicator of donor renal lesions, ischemia
      reperfusion injury and immunological aggression.
AB  - BACKGROUND: Early proteinuria is associated with reduced long-term graft
      survival. However, the determinants and mechanisms of proteinuria early after
      transplantation have not been identified. METHODS: Parameters associated with
      proteinuria within the first 3 months following transplantation were
      retrospectively assessed among 484 renal transplant recipients. RESULTS:
      Proteinuria was more abundant in patients with a history of two or more rejection
      episodes (0.42 +/- 0.68 vs 0.18 +/- 0.39 g/d; P = .02). Proteinuria was greater
      when donor age was 60 or more (OR: 4.43; P = .003), when recipient death was due
      to cardiovascular causes (OR: 1.98; P = .002), or when cold (OR: 1.77; P = .006)
      or warm (1.21; P = .09) ischemia times were prolonged. CONCLUSIONS: Proteinuria
      early after transplantation was related to pretransplant renal lesions, ischemia
      reperfusion, and immunologic injuries.

PMID- 16980079
TI  - Recurrent anemia in kidney transplant recipients with parvovirus B19 infection.
AB  - Parvovirus B19 (PV B19) infection is known to cause acute anemia in solid organ
      transplant recipients. Intravenous immunoglobulin combined with reduction of
      immunosuppression may be of benefit to clear the infection. However, PV B19
      associated anemia can be recurrent. We describe three renal transplant recipients
      with a PV B19 infection. These patients showed recurrent anemia with episodes
      separated by as much as several months.

PMID- 16980080
TI  - Cytomegalovirus prophylaxis with intravenous polyvalent immunoglobulin in high
      risk renal transplant recipients.
AB  - Cytomegalovirus (CMV) seronegative renal allograft recipients (R-), particularly
      those with a graft from a CMV-seropositive donor (D+), are at high risk for
      primary CMV infection. CMV resistance to antiviral oral therapy is an emerging
      problem in renal transplantation, prompting development of new prophylactic
      strategies. We retrospectively studied the 1-year posttransplantation incidence
      of CMV infection in high-risk renal transplant recipients, in whom polyvalent
      intravenous immunoglobulins (IVIg) were used as prophylaxis. Forty R- patients
      received immunoprophylaxis by polyvalent IVIg (0.25 g/kg weekly for 8 weeks,
      starting on the operative day). CMV serological tests remained negative in eight
      patients (20%). Eight patients (20%) had asymptomatic CMV infection while 24
      (60%) developed CMV syndrome and were treated with gancyclovir (10 mg/kg/day
      intravenously for 3 weeks). None had CMV disease or opportunistic infection. Six
      patients (15%) had biopsy-proven acute rejection, which followed CMV syndrome in
      three cases. One-year renal allograft and patient survivals were 95% and 97.5%,
      respectively. Mean serum creatinine level was 124 +/- 33 micromol/L at 1 year.
      Clinical tolerance of IVIg was excellent, without any episode of acute renal
      failure. Polyvalent IVIg provides effective prophylaxis in renal transplant
      recipients at high risk for CMV infection and is associated with excellent 1-year
      allograft survival. Because of their immunomodulatory functions, IVIg may have a
      beneficial effect on the incidence of acute and chronic rejection and allograft
      survival. A randomized prospective study is required to evaluate long-term
      effects of CMV prophylaxis with polyvalent IVIg compared to antiviral agents in
      renal transplant recipients.

PMID- 16980081
TI  - Expression of TGFbeta-1 and Type I TGFbeta-receptor on sequential biopsies of
      renal transplants with chronic allograft nephropathy.
AB  - The aim of this study was to determine the expression of transforming growth
      factor-beta (TGFbeta)-1 and type I TGFbeta-receptor on sequential biopsies from
      renal transplants with and without chronic allograft nephropathy. Twenty-four
      renal transplant recipients entered the study. They underwent sequential biopsies
      performed before (T1: 1.44 +/- 1.2 months) and 6 months after (T2: 15.96 +/- 7.2
      months) transplantation. Lesions were graded according to the criteria of the
      Banff classification. C4d was detected by fluorescence microscopy.
      Immunohistochemistry was performed in order to identify cells expressing TGFbeta
      1 and type I TGFbeta-receptor. In normal renal tissue (n = 4), TGFbeta-1 is
      expressed by tubular epithelial cells and endothelial cells lining glomerular and
      peritubular capillaries, whereas type 1 TGFbeta-receptor is expressed by tubular
      epithelial cells and smooth muscle cells in the media of arteries. In recipients
      with chronic allograft nephropathy (group 1, n = 14), diffuse epithelial
      expression of both molecules was found in more patients at T2 than at T1 (42.8%
      vs 21.4%). In contrast, this pattern of expression remained stable or decreased
      over time in recipients with long-term normal transplants (group 2, n = 10).
      Furthermore, type 1 TGFbeta-receptor was detected on the smooth muscle cells of
      arteries in 12/14 (85.7%) of recipients in group 1 and only in 4/9 (44.4%) of
      recipients in group 2. No relationship was noticed with regard to C4d deposits.
      These data suggest that the synthesis of TGFbeta-1 and type I TGFbeta-receptor
      increases over time in recipients developing chronic allograft nephropathy.
      Further studies are in progress in order to quantify mRNA of both molecules with
      real-time polymerase chain reaction.

PMID- 16980082
TI  - C4d: a marker for hepatic transplant rejection.
AB  - BACKGROUND: Acute rejection is still a common complication of hepatic
      transplantation. The diagnosis, based on the histological examination of the
      graft, may be difficult to confirm in the setting of combined hepatitis C virus
      infection. The presence of C4d in the portal capillaries could facilitate
      differentiation between acute rejection and relapsed hepatitis C. The deposit of
      C4d provides evidence of activation of humoral immunity. To attempt to confirm
      this hypothesis, we searched for the presence of C4d in posttransplant hepatic
      biopsies. METHODS: Thirty-six biopsies from 34 patients were analyzed
      retrospectively. The samples had been requested for one of the following reasons:
      suspected rejection, relapsed hepatitis C infection, or systematic check-up 1
      year after the transplant. RESULTS: C4d expression was common in biopsies
      classified as acute rejection (33%) and chronic rejection (100%). C4d was never
      detected in the event of recurrent hepatitis C infection without rejection.
      CONCLUSION: These results, which are comparable to recently published data, give
      credence to the theory that C4d could be used as a marker for rejection following
      hepatic transplantation.

PMID- 16980083
TI  - Monitoring HCMV infection with quantitative real-time PCR in HCMV-positive
      orthotopic liver transplant recipients, and predictive factors for treatment of
      the first episode of HCMV viremia.
AB  - We evaluated the relevance of human cytomegalovirus (HCMV) monitoring with
      quantitative real-time polymerase chain reaction in 42 consecutive HCMV positive
      liver transplant patients, and we analyzed the factors that determined the
      treatment of the first episode of HCMV DNAemia. No patients received anti-HCMV
      prophylaxis. HCMV infection monitoring was assessed every 2 weeks until day 90
      and thereafter at every 3 to 4 weeks until day 180. HCMV infection was detected
      among 27 patients (64%, ie, 92/380 samples). Of these, 12 had their first HCMV
      DNAemia treated with IV gancyclovir (group I), whereas the other 15 patients were
      not treated (group II). Immunosuppressive treatment was not modified in cases of
      HCMV DNAemia. The median time between transplantation to the first CMV DNAemia
      was 37 days in group I and 52 days in group II (NS). Median HCMV viral load,
      whatever the treatment group and whatever the time of DNAemia, was 3 log
      copies/mL (0.48 to 5.80). Median HCMV viral load of the first positive DNAemia
      was 3.45 log copies/mL (1.69 to 5.80) in group I and 2.70 log copies/mL (1.15 to
      3.94) in group II (P = .01). Even though liver enzymes were increased in almost
      all patients presenting with HCMV infection, comparison of liver-enzyme levels
      and hematological parameters between the two groups at first HCMV viremia showed
      that alkaline phosphatase levels were significantly higher (P = .0011) and
      hemoglobin levels were significantly lower in group I patients (P = .0443). The
      only factor that predicted treatment for the first episode of HCMV DNAemia was an
      alkaline phosphatase level >150 UI/mL at the time of the first HCMV reactivation
      [odds ratio 20 (1.96 to 203.3); P = .01].

PMID- 16980084
TI  - Predictive factors for cytomegalovirus infection after orthotopic liver
      transplantation using an ultrasensitive polymerase chain reaction assay.
AB  - The predictive factors for cytomegalovirus (CMV) infection in de novo liver
      transplant patients were determined at 3 months posttransplantation. We included
      all consecutive patients except those who died or who had lost their graft within
      1 month posttransplant. We recorded both donor (D) and recipient (R) data.
      Immunosuppression utilized tacrolimus, steroids, with or without mycophenolate
      mofetil, and/or induction therapy with anti-CD25 monoclonal antibodies. CMV
      prophylaxis was administered only to those at high risk of CMV infection, namely,
      D+/R- patients. These cases received intravenous ganciclovir at 500 mg/d for the
      first 2 weeks followed by oral ganciclovir at 500 mg for the following 3 months.
      The median time to CMV infection was 1 month. The significant predictive factors
      for CMV infection were D/R CMV status, (P = .002): D+/R+ versus other patients (P
      = .01), D-/R- versus other patients (P = .002), D+ versus D- (P = .009). In
      addition infection was associated with the original liver disease (hepatitis C
      virus infection or alcohol-related cirrhosis; P = .03), R+ vs. R- (P = .03),
      donor age (<45 or >45 years; P = .01), lymphocyte count at M2 (< or >1300/mm(3);
      P = .02), hemoglobin levels at 1 and 3 months, and platelet and white blood cell
      counts at day 7. The independent predictive factors were recipient CMV sero
      status (R+ vs R-; odds ratio = 10.2), donor age >45 years (odds ratio = 11.4) and
      lymphocyte count at M2 <1300/mm(3) (odds ratio = 7.33). This study showed that
      the major factors associated with CMV infection were recipient CMV status, donor
      age, and lymphocyte count.

PMID- 16980086
TI  - Chimerism in lymphoid tissues and donor-specific antibody response after
      injection of allogenic splenic dendritic cells from Fischer rats to Lewis
      recipients.
AB  - The aim of this work was to study cellular chimerism achieved in lymphoid tissues
      and production of antidonor lymphocyte antibodies after injection of splenic
      dendritic cells (DCs) from Fischer F344 rats to Lewis recipients, a model of
      chronic rejection. DCs isolated from the spleen expressed OX62 (95%), CD80 (70%),
      and CD86 (80%). Two doses of these nonplasmacytoid splenic DCs from Fischer rats
      (2 x 10(6) and 5 x 10(6)), which had been labeled ex vivo with a TRITC
      fluorochrome (PKH26), were injected to Lewis recipients. Using fluorescence
      microscopy TRITC positive cells were localized at day 15 and day 45 in frozen
      sections from spleen, thymus, mesenteric lymph nodes, heart, liver, kidney, and
      skin (n = 5 per group). Donor-specific antibodies were sought with flow
      cytometric crossmatches in serum samples taken at 7, 15, 30, and 45 days. TRITC
      positive DCs were essentially localized in the spleen, the thymus, and lymph
      nodes of Lewis recipients. The majority of DCs were detected in the spleen (14.9
      +/- 3.3 and 14.3 +/- 0.9 DCs/per high power field respectively at day 45). A
      significant number of DCs was also detected in the thymus and mesenteric lymph
      nodes at both times. Only some scattered TRITC-positive cells were observed in
      other organs. The number of DCs was stable over time and did not depend on the
      injected dose. A positive flow cytometric cross-match was observed at day 30 in
      all recipients independent of the injected dose. These data showed that 2 x 10(6)
      mature, nonplasmocytoid DCs from F344 rats injected to Lewis recipients induced
      stable chimerism in primary and secondary lymphoid organs and a humoral response
      to donor antigens.

PMID- 16980085
TI  - Predictive factors for anemia within the first year after orthotopic liver
      transplantation.
AB  - We sought to determine the prevalence and predictive factors for posttransplant
      anemia within the first year after orthotopic liver transplant (OLT) among 97
      consecutive patients. Anemia was defined at months 6 and 12 according to the WHO
      criteria, that is, a hemoglobin (Hb) level of <12 g/dL for women and <13 g/dL for
      men. Immunosuppression relied on tacrolimus and steroids, with or without
      mycophenolate mofetil. Anemia was present in 64.5%, 50%, and 52.8% of patients
      pre-OLT versus 6 and 12. Thirty-three percent (month 6) and 30.3% (month 12) of
      anemic patients received recombinant erythropoietin therapy. A multivariate
      analysis revealed that the independent predictive factors for anemia at month 6
      were mean corpuscular volume (<85 fL) at day 7, daily steroid dosage (<0.3
      mg/kg), serum creatinine (>130 mumol/L), and Hb level (<11 g/dL) at month 1.
      Independent predictive factors for anemia at month 12 were daily steroid dosage
      at month 1 (<0.3 mg/kg), hematocrit at month 1 (<33%), red blood cell count at
      month 6 (<3.75 T/L), daily dosage at month 1 of cyclosporine or tacrolimus, and
      etiology of end-stage liver disease other than alcohol abuse. We concluded that
      anemia was highly prevalent within the first year of post-OLT. This observation
      deserves further investigation and appropriate treatment.

PMID- 16980087
TI  - Evaluation of an immunoassay (Abbott-IMX Analyzer) allowing routine determination
      of sirolimus: comparison with LC-MS method.
AB  - BACKGROUND: The use of the immunosuppressive agent sirolimus is increasing in
      renal transplantation but its monitoring often requires high-performance liquid
      chromatography (HPLC) with ultra-violet (UV) or tandem mass spectrometric (MS-MS)
      detection. The aim of this study was to compare a new microparticle enzyme
      immunoassay (MEIA, Microparticle Enzyme Immunoassay) on IMx Abbott Analyser with
      a liquid chromatography-mass spectometry (LC-MS) method. METHOD: The accuracy of
      immunoassay analytical performance including within run and between run
      imprecision and linearity was tested. For comparison studies, sirolimus level was
      then determined with the two methods on 98 samples from 52 transplant patients.
      RESULTS: Total intra-assay and inter-assay variation coefficients were below 10%
      at the three levels tested, and the coefficient of linearity was r = 0.99. The
      values obtained were highly correlated with the LC-MS method (MEIA = 1.02LC-MS +
      0.91; r(2) = 0.87). As a result, the immunoassay showed good performance, and
      clinical sample measurements were not affected by the method. The MEIA may be a
      useful alternative for routine monitoring of sirolimus.

PMID- 16980089
TI  - Time for a debate on health care in the USA.

PMID- 16980088
TI  - Effects of the molecular weight of peg molecules (8, 20 and 35 KDA) on cell
      function and allograft survival prolongation in pancreatic islets
      transplantation.
AB  - The normopotassic solution SCOT (Macopharma, France) used for the isolation of
      the islets of Langerhans may improve both graft function and survival. We believe
      that this is due to the immunoprotective properties of polyethyleneglycol (PEG)
      (20 kDa; 1.5 mM/L), which is contained in this solution. However, the optimal PEG
      chain length remains to be determined. Three extracellular type solutions (SCOT
      without PEG) containing various PEG-8 kDa, 20 kDa, or 35 kDa- at 1.5 mM/L were
      compared in vitro for viscosity and osmolarity as well as in vivo using a murine
      model of pancreatic islet allotransplantation. We compared the effects of the
      various solutions on functional cell recovery (primary nonfunction rate, PNF) and
      immunoprotection (allograft survival time). We showed that the viscosity of PEG
      35 kDa solutions was too high for physiological use. PEG 20 kDa solution provided
      the best graft function (0% PNF, P < .05). PEG 8 kda and 20 kDa solutions
      significantly increased allograft survival time compared to the PEG 35 kDa
      solution (P < .05). Graft survival was similar with PEG 20 kDa and PEG 8 kDa
      solutions: 27.50 +/- 3.70 days versus 23.13 +/- 4.39 days (NS). However, the
      number of PNF with PEG 8 kDa solution (50%) was significantly higher (P < .01)
      than that with the PEG 20 kDa solution (0%). These preliminary results indicated
      that the optimal chain length at 1.5 mM/L of PEG is 20 kDa.

PMID- 16980090
TI  - A crowded field starts WHO's Director-General election.

PMID- 16980091
TI  - XDR-TB--a global threat.

PMID- 16980092
TI  - H5N1 vaccines: how prepared are we for a pandemic?

PMID- 16980093
TI  - The early invasive strategy revisited: FRISC II at 5 years.

PMID- 16980094
TI  - Valvular heart diseases in elderly people.

PMID- 16980095
TI  - When does a fingerprint constitute a diagnostic?

PMID- 16980096
TI  - Compliance with osteoporosis therapy is the weakest link.

PMID- 16980097
TI  - Shocked, shot, and pardoned.

PMID- 16980099
TI  - John Idoko.

PMID- 16980100
TI  - Cuttings.

PMID- 16980101
TI  - German medical hierarchy: the ladder to quality of life?

PMID- 16980102
TI  - Emerging concerns about Iran's scientific and medical future.

PMID- 16980103
TI  - Helicobacter pylori and gastro-oesophageal reflux disease.

PMID- 16980105
TI  - Altruistic kidney donation.

PMID- 16980106
TI  - Noma.

PMID- 16980107
TI  - Mismanagement as a prelude to privatisation of the UK NHS.

PMID- 16980108
TI  - Extrapulmonary manifestations of severe RSV bronchiolitis.

PMID- 16980109
TI  - Noma.

PMID- 16980110
TI  - Investigation of cholesterol gallstone disease.

PMID- 16980111
TI  - Provoking the desire.

PMID- 16980112
TI  - Funding for clinical research in the UK.

PMID- 16980113
TI  - Funding for clinical research in the UK.

PMID- 16980114
TI  - Safety and immunogenicity of an inactivated adjuvanted whole-virion influenza A
      (H5N1) vaccine: a phase I randomised controlled trial.
AB  - BACKGROUND: Avian influenza A virus H5N1 has caused widespread infections that
      have resulted in severe disease or death in poultry and wild birds as well as
      human beings. This virus has the potential to emerge as a pandemic threat and
      H5N1 vaccines are being developed in many countries. Our aim was to assess the
      safety and immunogenicity of an inactivated adjuvanted whole-virion H5N1 vaccine.
      METHODS: A stratified randomised, placebo-controlled, double-blind phase I
      clinical trial was done in 120 volunteers aged 18-60 years. Volunteers were
      assigned to receive two doses of placebo (n=24) or an inactivated whole-virion
      influenza A (H5N1) vaccine with 1.25 microg (24), 2.5 microg (24), 5 microg (24),
      or 10 microg (24) haemagglutinin per dose with aluminium hydroxide adjuvant on
      day 0 and 28. Serum samples were obtained on day 0, 14, 28, 42, and 56 for
      haemagglutination inhibition and virus neutralisation assays. This trial is
      registered with the ClinicalTrials.gov registry with the number NCT00356798.
      FINDINGS: All four formulations of vaccines were well tolerated. No serious
      adverse event was reported and most local and systemic reactions were mild and
      transient. All formulations induced antibody responses after the first dose; the
      highest immune response of 78% seropositivity was seen in the 10 mug group after
      two vaccine doses. Two individuals dropped out: one in the 1.25 microg group
      (withdrew consent) and one in the 10 microg group (discontinued); one individual
      was also excluded from the final analysis. INTERPRETATION: A two-dose regimen of
      an adjuvanted 10 microg inactivated whole-virion H5N1 vaccine met all European
      regulatory requirements for annual licensing of seasonal influenza vaccine. Lower
      doses of this vaccine could achieve immune responses equivalent to those elicited
      by adjuvanted or non-adjuvanted split-virion vaccines. The use of a whole virion
      vaccine could be more adaptable to the antigen-sparing strategy recommended by
      WHO for protection against an influenza pandemic.

PMID- 16980115
TI  - 5-year outcomes in the FRISC-II randomised trial of an invasive versus a non
      invasive strategy in non-ST-elevation acute coronary syndrome: a follow-up study.
AB  - BACKGROUND: The FRISC-II invasive trial compared an early invasive with a non
      invasive strategy in terms of death and myocardial infarction in non-ST-elevation
      acute coronary syndrome. We present 5-year follow-up results, overall and in
      subgroups based on recommended risk stratification criteria. METHODS: In the
      FRISC-II trial, 2457 patients with non-ST-elevation acute coronary syndrome were
      randomised to early invasive strategy (coronary angiography and, if appropriate,
      revascularisation, within 7 days from admission) or non-invasive primarily
      medical strategy. Risk stratification was done on the basis of risk indicators at
      randomisation: age older than 65 years, male sex, diabetes mellitus, previous
      myocardial infarction, ST-segment depression, raised troponin concentration
      (>0.03 mug/L), and raised C-reactive protein or interleukin 6. Information on
      events after 24 months was taken from national registries. Analyses were done on
      an intention-to-treat basis. FINDINGS: At 5 years the groups differed in terms of
      the primary composite endpoint of death, myocardial infarction, or both (invasive
      217, 19.9 %; noninvasive 270, 24.5 %; risk ratio 0.81; 95% CI 0.69-0.95;
      p=0.009). 5-year mortality was 117 (9.7%) in the invasive group compared with 124
      (10.1%) in the noninvasive group (0.95; 0.75 -1.21; p=0.693). Rates of myocardial
      infarction were 141 (12.9 %) in the invasive and 195 (17.7%) in the non-invasive
      group (0.73; 0.60-0.89; p=0.002). The benefit of the invasive strategy was
      confined to male patients, non-smokers, and patients with two or more risk
      indicators. INTERPRETATION: The 5-year outcome of this trial indicates sustained
      benefit of an early invasive strategy in patients with non-ST-elevation acute
      coronary syndrome at moderate to high risk.

PMID- 16980116
TI  - Burden of valvular heart diseases: a population-based study.
AB  - BACKGROUND: Valvular heart diseases are not usually regarded as a major public
      health problem. Our aim was to assess their prevalence and effect on overall
      survival in the general population. METHODS: We pooled population-based studies
      to obtain data for 11 911 randomly selected adults from the general population
      who had been assessed prospectively with echocardiography. We also analysed data
      from a community study of 16 501 adults who had been assessed by clinically
      indicated echocardiography. FINDINGS: In the general population group, moderate
      or severe valve disease was identified in 615 adults. There was no difference in
      the frequency of such diseases between men and women (p=0.90). Prevalence
      increased with age, from 0.7% (95% CI 0.5-1.0) in 18-44 year olds to 13.3% (11.7
      15.0) in the 75 years and older group (p<0.0001). The national prevalence of
      valve disease, corrected for age and sex distribution from the US 2000
      population, is 2.5% (2.2-2.7). In the community group, valve disease was
      diagnosed in 1505 (1.8% adjusted) adults and frequency increased considerably
      with age, from 0.3% (0.2-0.3) of the 18-44 year olds to 11.7% (11.0-12.5) of
      those aged 75 years and older, but was diagnosed less often in women than in men
      (odds ratio 0.90, 0.81-1.01; p=0.07). The adjusted mortality risk ratio
      associated with valve disease was 1.36 (1.15-1.62; p=0.0005) in the population
      and 1.75 (1.61-1.90; p<0.0001) in the community. INTERPRETATION: Moderate or
      severe valvular diseases are notably common in this population and increase with
      age. In the community, women are less often diagnosed than are men, which could
      indicate an important imbalance in view of the associated lower survival. Valve
      diseases thus represent an important public-health problem.

PMID- 16980117
TI  - Identification of diagnostic markers for tuberculosis by proteomic fingerprinting
      of serum.
AB  - BACKGROUND: We investigated the potential of proteomic fingerprinting with mass
      spectrometric serum profiling, coupled with pattern recognition methods, to
      identify biomarkers that could improve diagnosis of tuberculosis. METHODS: We
      obtained serum proteomic profiles from patients with active tuberculosis and
      controls by surface-enhanced laser desorption ionisation time of flight mass
      spectrometry. A supervised machine-learning approach based on the support vector
      machine (SVM) was used to obtain a classifier that distinguished between the
      groups in two independent test sets. We used k-fold cross validation and random
      sampling of the SVM classifier to assess the classifier further. Relevant mass
      peaks were selected by correlational analysis and assessed with SVM. We tested
      the diagnostic potential of candidate biomarkers, identified by peptide mass
      fingerprinting, by conventional immunoassays and SVM classifiers trained on these
      data. FINDINGS: Our SVM classifier discriminated the proteomic profile of
      patients with active tuberculosis from that of controls with overlapping clinical
      features. Diagnostic accuracy was 94% (sensitivity 93.5%, specificity 94.9%) for
      patients with tuberculosis and was unaffected by HIV status. A classifier trained
      on the 20 most informative peaks achieved diagnostic accuracy of 90%. From these
      peaks, two peptides (serum amyloid A protein and transthyretin) were identified
      and quantitated by immunoassay. Because these peptides reflect inflammatory
      states, we also quantitated neopterin and C reactive protein. Application of an
      SVM classifier using combinations of these values gave diagnostic accuracies of
      up to 84% for tuberculosis. Validation on a second, prospectively collected
      testing set gave similar accuracies using the whole proteomic signature and the
      20 selected peaks. Using combinations of the four biomarkers, we achieved
      diagnostic accuracies of up to 78%. INTERPRETATION: The potential biomarkers for
      tuberculosis that we identified through proteomic fingerprinting and pattern
      recognition have a plausible biological connection with the disease and could be
      used to develop new diagnostic tests.

PMID- 16980118
TI  - Systemic lupus erythematosus and blood type.

PMID- 16980119
TI  - Panic disorder.
AB  - Panic disorder is a common mental disorder that affects up to 5% of the
      population at some point in life. It is often disabling, especially when
      complicated by agoraphobia, and is associated with substantial functional
      morbidity and reduced quality of life. The disorder is also costly for
      individuals and society, as shown by increased use of health care, absenteeism,
      and reduced workplace productivity. Some physical illnesses (eg, asthma) commonly
      occur with panic disorder, and certain lifestyle factors (eg, smoking) increase
      the risk for the disorder, but causal pathways are still unclear. Genetic and
      early experiential susceptibility factors also exist, but their exact nature and
      pathophysiological mechanisms remain unknown. Despite an imprecise, although
      increased, understanding of cause, strong evidence supports the use of several
      effective treatments (eg, pharmacological, cognitive-behavioural). The adaptation
      and dissemination of these treatments to the frontlines of medical-care delivery
      should be urgent goals for the public-health community.

PMID- 16980120
TI  - Politics and health outcomes.
AB  - The aim of this study was to examine the complex interactions between political
      traditions, policies, and public health outcomes, and to find out whether
      different political traditions have been associated with systematic patterns in
      population health over time. We analysed a number of political, economic, social,
      and health variables over a 50-year period, in a set of wealthy countries
      belonging to the Organisation for Economic Co-operation and Development (OECD).
      Our findings support the hypothesis that the political ideologies of governing
      parties affect some indicators of population health. Our analysis makes an
      empirical link between politics and policy, by showing that political parties
      with egalitarian ideologies tend to implement redistributive policies. An
      important finding of our research is that policies aimed at reducing social
      inequalities, such as welfare state and labour market policies, do seem to have a
      salutary effect on the selected health indicators, infant mortality and life
      expectancy at birth.

PMID- 16980121
TI  - A case of breast carcinoma, chemotherapy, and acute appendicitis.

PMID- 16980122
TI  - Progress in plant CACTA elements.
AB  - Transposable elements are DNA fragments that can insert new chromosomal
      locations. On the basis of the mechanism of transposition, transposable elements
      were divided into two classes. Class 1 elements were retroelements that used
      reverse transposase to transpose by an RNA intermediate. Class 2 elements or DNA
      transposons transposed directly from DNA to DNA. Of the Class 2 elements, CACTA
      superfamily, so far identified exclusively in plants and previously regarded as
      low-copy-transposon for the conserved mechanism of propagation, recently received
      considerable interest because of their increasing evidence reiterating their high
      copies in some plant genomes. This article aimed at outlining CACTA elements with
      regard to their structure, transposition, and utilization.

PMID- 16980123
TI  - Linkage and association between CA repeat polymorphism of the TNFR2 gene and
      obesity phenotypes in two independent Caucasian populations.
AB  - Previously, our group has reported a suggestive linkage evidence of 1p36 with
      body mass index (BMI) (LOD = 2.09). The tumor necrosis factor receptor 2 (TNFR2)
      at 1p36 is an excellent positional and functional candidate gene for obesity. In
      this study, we have investigated the linkage and association between the TNFR2
      gene and obesity phenotypes in two large independent samples, using the
      quantitative transmission disequilibrium tests (QTDT). The first group was made
      up of 1,836 individuals from 79 multi-generation pedigrees. The second group was
      a randomly ascertained set of 636 individuals from 157 US Caucasian nuclear
      families. Obesity phenotypes tested include BMI, fat mass, and percentage fat
      mass (PFM). A significant result (P = 0.0056) was observed for linkage with BMI
      in the sample of the multigenerational pedigrees. Our data support the TNFR2 gene
      as a quantitative trait locus (QTL) underlying BMI variation in the Caucasian
      populations.

PMID- 16980124
TI  - Effects of pharmacological concentrations of estrogens on growth of 3AO human
      ovarian cancer cells.
AB  - During the past two decades, the knowledge of the molecular mechanism by which
      estrogens exert various functions in different tissues and organs has evolved
      rapidly. Recent reports demonstrated that estrogen could decrease the cell growth
      in several types of cancer cells, including ovarian cancer cells. Though
      experiments explored the possible mechanism of the inhibitory effect, the exact
      mechanism is responsible for the effect, which remains unclear. The ovary is the
      main source of the estrogen, estrogen receptor is expressed in several ovarian
      cell types, including ovarian surface epithelium, the tissue of origin of
      approximately 90% of the ovarian cancers. It was of great interest to analyze the
      effects of 17beta-estradiol (E2) on apoptosis of ovarian cancer cells, and the
      identification of E2-regulated specific genes involved in epithelial
      proliferation apoptosis, thus may be a clue for understanding the progression of
      ovarian cancer and for the design of new target therapies. To elucidate the
      mechanism involved, effects of pharmacological concentrations of estrogen were
      studied in human ovarian cancer cell line 3AO cells. Inhibition of cellular
      growth of 3AO cells was seen with E2 at concentrations higher than 0.1
      micromol/L. The estrogen receptor inhibitor ICI 182780 cannot block the
      inhibitory effect of E2. It was surprising to find that ICI 182780 itself can
      inhibit the growth of 3AO cells, and had a collaborative effect with E2. The
      decreased cell growth induced by E2 was shown to be apoptosis as analyzed by flow
      cytometry. ERbeta was detected in the 3AO ovarian cancer cell line but not
      ERalpha. The expression of ERbeta was weak, which may partially explain why high
      but not low dose of E2 needed to induce the apoptosis of 3AO cells. We also
      observed that membrane impermeable E2, E2-BSA have lost growth inhibitory on 3AO
      cells, which excluded the membrane effect of E2 as previously reported by many
      investigators. The p38 kinase inhibitor, SB203580 were partially protected 3AO
      cells against growth inhibition by E2, while inhibitor of JNK, SP600125 enhanced
      cell death induced by E2. These results showed that MAPK is implicated in
      cellular processes involving apoptosis.

PMID- 16980125
TI  - Structure of the mitochondrial DNA control region of the sinipercine fishes and
      their phylogenetic relationship.
AB  - The mitochondrial DNA control region of Siniperca chuatsi, S. kneri, S.
      scherzeri, S. obscura, S. undulata, Coreosiniperca roulei and Coreoperca
      whiteheadi were amplified by PCR amplification and directly sequenced. The mtDNA
      control region of the sinipercine fishes could be separated into three domains,
      namely, the terminal associated sequence domain, the central conserved sequence
      domain and the conserved sequence block domain. The extended terminal associated
      sequence (ETAS), three conserved sequence blocks (CSB-F, CSB-E, CSB-D) in the
      central conserved sequence domain and three conserved sequence blocks (CSB1,
      CSB2, CSB3) in the conserved sequence block domain were also identified. The
      phylogenetic relationships among these sinipercine fishes were constructed
      through neighbor-joining and maximum parsimony methods using Percidae and
      Serranidae as outgroups. Results showed that sinipercine fishes were a
      monophyletic group, with Siniperca forming one group, and Coreoperca forming
      another group. Coreosiniperca roulei did not form an independent group but was
      merged into the genus Siniperca. Thus it should be renamed as Siniperca roulei.

PMID- 16980126
TI  - The correlation of reproduction-related gene expression with germ cell number in
      DM and PLL gilts.
AB  - In this study, the ovarian germ cell number was counted in 3-week-old Duroc x
      Meishan (DM, n=30) and PIC x (Landrace x Large White) (PLL, n=53) gilts, and the
      mRNA expression levels of four reproduction-related genes were investigated by
      quantitative RT-PCR. Correlation of germ cell number with the expression level of
      these genes was analyzed. Results showed that the germ cell number of DM was
      significantly higher than that of PLL gilts (P<0.01), although there was no
      significant difference between the ovarian weight of DM and PLL gilts (P=0.269).
      No significant correlation existed between germ cell number and ovarian weight in
      the two gilt groups (R=0.335, P=0.07; R=0.119, P=0.398, respectively). A
      significant correlation was found between the germ cell number and expression
      level of ESR and IGF1R mRNA in DM gilts (R=0.648, P<0.05; R=0.757, P<0.01,
      respectively), but the correlation between the germ cell number and expression
      level of FSHR and INHBA mRNA did not reach statistical significance. Significant
      correlation was found between the germ cell number and the expression level of
      ESR, FSHR, and IGF1R mRNA in PLL gilts (R=0.435, P<0.01; R=0.438, P<0.01;
      R=0.292, P<0.05, respectively), but not with INHBA mRNA in PLL gilts.

PMID- 16980127
TI  - The tissue distribution and developmental changes of ghrelin mRNA expression in
      sheep.
AB  - Male Kazak sheep and Xinjiang fine wool sheep, six for each different age group
      (days 2, 30, 60, 90 and 120), were used in the present study to investigate the
      tissue distribution and developmental changes of ghrelin mRNA expression in
      abomasum; however, there was no 120-day-old Kazak sheep. After measurement of
      body weight, the tissues such as hypothalamus, pituitary, heart, liver, rumen,
      reticulum, omasum, abomasum, duodenum, and longissimus dorsi muscle were sampled.
      And the total RNA of different tissues was extracted to determine the abundance
      of ghrelin mRNA by RT-PCR and real-time PCR. The results showed that (1) for both
      breeds, body weight among different ages was significantly different (P<0.05).
      And from day 30 to 90, the body weight of Kazak was significantly higher than
      that of Xinjiang (P<0.01); (2) Ghrelin mRNA existed in all the above tissues and
      was significantly higher in the abomasum than in other tissues (P<0.05); (3) the
      temporal patterns of abomasum ghrelin mRNA expression in Kazak and Xinjiang were
      similar. From day 2 to 60 in Kazak and 2 to 90 in Xinjiang, there was a steady
      increase in the ghrelin mRNA level. By day 60 in Kazak and day 90 in Xinjiang,
      the level reached a plateau and remained steady. These results also demonstrated
      that from birth to day 90, ghrelin mRNA level was significantly higher in Kazak
      than in Xinjiang (P<0.01).

PMID- 16980128
TI  - RFLP and AFLP analysis of inter- and intraspecific variation of Brassica rapa and
      B. napus shows that B. rapa is an important genetic resource for B. napus
      improvement.
AB  - Fingerprinting of 29 accessions of oilseed rape, including seven accessions of
      Brassica napus, and 22 accessions of B. rapa (B. campestris) from Europe, North
      America, and China was analyzed using RFLP and AFLP markers. In total, 1,477
      polymorphic RFLP bands and 183 polymorphic AFLP bands from 166 enzyme-probe
      combinations and two pairs of AFLP primers, respectively, were scored for the 29
      accessions. On average, RFLP analysis showed that the Arabidopsis EST probe
      detected more polymorphic bands in Brassica than the random genomic probe
      performed. More polymorphic RFLP markers were detected with the digestion of EcoR
      I or BamH I than HindIII. According to the number of bands amplified from each
      accession, the copy numbers of each gene in the genomes of B. rapa and B. napus
      were estimated. The average copy numbers in B. rapa of China, B. rapa of Europe,
      and B. napus, were 3.2, 3.1, and 2.9, respectively. Genetic distance based on the
      AFLP data was well correlated with that based on the RFLP data (r = 0.72,
      P<0.001), but 0.39 smaller on average. Genetic diversity analysis showed that
      Chinese B. rapa was more polymorphic than Chinese B. napus and European
      materials. Some European B. napus accessions were clustered into European B.
      rapa, which were distinctly different from Chinese B. napus. The larger
      variations of Chinese accessions of B. rapa suggest that they are valuable in
      oilseed rape breeding. Novel strategies to use intersubgenomic heterosis between
      genome of B. rapa (A(r)A(r)) and genome of B. napus (A(n)A(n)C(n)C(n)) were
      elucidated.

PMID- 16980129
TI  - QTL analysis for flag leaf characteristics and their relationships with yield and
      yield traits in rice.
AB  - Photosynthesis of carbohydrate is the primary source of grain yield in rice
      (Oryza sativa L.). It is important to genetically analyze the morphological and
      the physiological characteristics of functional leaves, especially flag leaf, in
      rice improvement. In this study, a recombinant inbred population derived from a
      cross between an indica (O. sativa L. ssp. indica) cultivar and a japonica (O.
      sativa L. ssp. japonica) cultivar was employed to map quantitative traits loci
      (QTLs) for the morphological (i.e., leaf length, width, and area) and
      physiological (i.e., leaf color rating and stay-green) characteristics of flag
      leaf and their relationships with yield and yield traits in 2003 and 2004. A
      total of 17 QTLs for morphological traits (flag leaf length, width, and area), 6
      QTLs for degree of greenness and 14 QTLs for stay-green-related traits (retention
      degrees of greenness, relative retention of greenness, and retention of the green
      area) were resolved, and 10 QTLs were commonly detected in both the years.
      Correlation analysis revealed that flag leaf area increased grain yield by
      increasing spikelet number per panicle. However, the physiological traits
      including degree of greenness and stay-green traits were not or negatively
      correlated to grain yield and yield traits, which may arise from the negative
      relation between degree of greenness and flag leaf size and the partial sterility
      occurred in a fraction of the lines in this population. The region RM255-RM349 on
      chromosome 4 controlled the three leaf morphological traits simultaneously and
      explained a large part of variation, which was very useful for genetic
      improvement of grain yield. The region RM422-RM565 on chromosome 3 was associated
      with the three stay-green traits simultaneously, and the use of this region in
      genetic improvement of grain yield needs to be assessed by constructing near
      isogenic lines.

PMID- 16980130
TI  - Salt induces expression of RH3.2A, encoding an H3.2-type histone H3 protein in
      rice (Oryza sativa L.).
AB  - Histone H3 is one of the four histones, along with H2A, H2B, and H4, which form
      the eukaryotic nucleosome octamer core. In this study, a new gene RH3.2A encoding
      an H3.2-type histone H3 protein from rice (Oryza sativa L.) was reported. RH3.2A
      was cloned through RT-PCR from salt-treated rice seedlings. This gene encoded a
      protein of 136 amino acid residues that were similar to some plant histone H3
      proteins reported previously. However, the cDNA sequence of RH3.2A and other rice
      H3 genes were different. Alignment of RH3.2A encoding protein with other plant
      histone H3 proteins revealed that three amino acid residues (32, 88, and 91) were
      markedly different between H3.1-type and H3.2-type proteins. The mRNA expression
      analysis of RH3.2A revealed that RH3.2A gene was upregulated by salt stress in
      rice roots and ABA treatment in seedlings. The potential role of RH3.2A during
      salt stress was discussed.

PMID- 16980131
TI  - Genetic analysis for F1 yield traits with conditional approach in island cotton
      (Gossypium barbadense L.).
AB  - A genetic model with additive, dominance and genotype x environment interaction
      effect was employed to analyze the 3-year data of F(1) hybrids from 5 x 4 diallel
      cross, whose parents were Island cotton and had different fruit branch types.
      Unconditional and conditional genetic variances were conducted for analyze
      genetic impacts of yield components on yield. Results of unconditional genetic
      variances showed that there were no additive variance of total lint yield. But
      conditional additive effects of total lint yield, when excluding the phenotype of
      boll weight, boll number at prefrost, boll number at postfrost, and lint yield at
      prefrost, indicated that improving the additive effects of the total lint yield
      was still possible. Crossing and selecting component traits with high
      contributive additive effects could obtain good offsprings. Yield components
      contributed large dominance effects to the heterosis of lint yield at prefrost
      and total lint yield in crosses. Yield component traits were controlled with each
      other. The traits having positive contributive effects could be applied to
      further improve target traits.

PMID- 16980132
TI  - Construction of fingerprinting and genetic diversity of mulberry cultivars in
      China by ISSR markers.
AB  - The ISSR fingerprintings of 24 mulberry cultivars were constructed. Totally 80
      bands were produced using 17 primers selected from 20 primers. Of them, 40 bands
      showed polymorphism. From the bands amplified, there were three independent ways
      to identify the mulberry varieties, such as unique ISSR markers, unique band
      patterns and a combination of the band patterns provided by different primers.
      ISSRs were very effective in differentiating the mulberry varieties. The mean
      genetic similarity coefficient, the mean Nei's gene diversity (h), and the mean
      Shannon's Information index (I) of mulberry cultivars were 0.8731, 0.1210, and
      0.1942, respectively. This suggests that the genetic diversity of mulberry
      cultivars was low and the genetic base was narrow. Both UPGMA cluster and PCA
      (Principal Coordinates Analysis) analysis showed clear genetic relationships
      among the 24 mulberry cultivars. The major clusters were related to known
      pedigree relationships.

PMID- 16980133
TI  - Parent-professional partnerships: bridging the disparate worlds of children,
      families, and professionals.

PMID- 16980134
TI  - Homeless adolescent mothers: a metasynthesis of their life experiences.
AB  - The purpose of this article was to synthesize the findings of six qualitative
      studies on homeless adolescent mothers. Metasynthesis was conducted using the
      meta-ethnographic approach of Noblit and Hare [Noblit, G., & Hare, R. (1988).
      Meta-ethnography: Synthesizing qualitative studies. Newbury Park, CA: Sage
      Publications]. Six reciprocal translations illuminating the experiences of
      homeless adolescent mothers emerged: being homeless, enduring abuse, lamenting
      lost years, searching for support, recreating self, and seeking a better life.
      The findings may be used by nurses working with this population as the basis for
      a framework of intervention strategies directed toward helping these mothers cope
      with their dual transitions into motherhood and adulthood while simultaneously
      being homeless.

PMID- 16980135
TI  - Parents of children with cancer: factors influencing their treatment decision
      making roles.
AB  - This study examined the factors that parents identified as influencing their role
      in treatment decision making (TDM) for their child with cancer. Content analysis
      of qualitative data from semistructured interviews with 36 parents as part of a
      mixed-methods study revealed numerous themes related to parents' TDM roles.
      Factors that were frequently identified included: relationship with the
      physician, nature of communication, trust in the physician, parents' and
      physician's knowledge and experience, and importance of parental role. Parents
      acknowledged a strong sense of responsibility and feeling of "ownership" of their
      child. Parents initially lacked knowledge and experience, but acquiring these
      over time contributed to a more active participation in TDM.

PMID- 16980136
TI  - Psychological adjustment in young children with chronic medical conditions.
AB  - Children with chronic medical conditions are at higher risk for behavioral and
      emotional problems compared to physically healthy children. This study used a
      conceptual model to examine factors associated with psychological adjustment in
      children aged 7-11 years old with any of four chronic illnesses. The variables
      most closely associated with child adjustment included the following: mothers'
      evaluation of the impact of the child's illness on the family; child's
      perceptions of parental acceptance; and child's self-perceptions of physical
      appearance, social acceptance, and athletic competence. These findings confirm
      the importance of maternal and child perceptions in understanding the
      psychological adjustment of children with chronic conditions.

PMID- 16980137
TI  - Preparing peer educators for teen HIV/AIDS prevention.
AB  - Adolescents, as a group, are at risk for contracting HIV/AIDS and other sexually
      transmitted diseases because of their developmental level, which often leads to
      impulsiveness and desire for experimentation. Finding ways to educate and
      motivate adolescents to avoid sexual risk behaviors is a challenge to pediatric
      nurses and teachers. Theoretically based peer education programs help change
      adolescent risk behaviors because of the influence of peers during adolescence.
      This article presents information on a project aiming to prepare peer leaders in
      an urban high school to become peer educators using the program Teens for AIDS
      Prevention. Nurses can play a major role in the planning, implementation, and
      evaluation of peer education programs to prevent adolescent risk behaviors.

PMID- 16980138
TI  - Children inhaling.

PMID- 16980139
TI  - An evidence-based approach to nasogastric tube management: special
      considerations.
AB  - Although there have been helpful literature reviews on pediatric nasogastric (NG)
      tube management, there is a lack of evidence with regards to special
      circumstances, such as at-risk patients with altered neurological status or
      developmental disabilities. At our hospital, an interdisciplinary Enteral Feeding
      Task Force was created to address the special needs and concerns of complex
      pediatric patients. We carefully weighed the evidence from the literature,
      incidents at our hospital and other children's hospitals, and a synthesis of
      expert opinion. This article describes our evidence-based process of policy
      revision, and it includes excerpts from our revised NG tube management policy.

PMID- 16980140
TI  - More medical journals should inform their contributors about three key principles
      of graph construction.
AB  - OBJECTIVES: To identify key principles of graph construction and to review
      guidance on graph construction provided by medical journals. STUDY DESIGN AND
      SETTING: Review of a prevailing model of graph comprehension and survey of
      authors' instructions for all 120 core medical journals as indexed by PubMed.
      RESULTS: Graph construction should meet three requirements for optimal graph
      comprehension: Data symbols should be clearly distinguishable to enable their
      visual detection. Second, the data should be arranged in such a way that
      estimation of values and important relationships in the data is facilitated, and
      third, there should be a full explanation of all graph elements and of how the
      data were obtained. Seven journals (5.8%) provided recommendations on graph
      construction. Six journals put emphasis primarily on the explanation of graph
      elements and, to a lesser extent, on the visual detection of data symbols.
      Recommendations of the seventh journal focused mostly on how to enhance
      estimation of important relationships. All journals presented single
      recommendations whose selection seemed unstructured and not based on key
      principles of graph construction. CONCLUSION: Medical journals should order their
      instructions according to the three key aspects of graph construction.

PMID- 16980141
TI  - Extreme between-study homogeneity in meta-analyses could offer useful insights.
AB  - OBJECTIVES: Meta-analyses are routinely evaluated for the presence of large
      between-study heterogeneity. We examined whether it is also important to probe
      whether there is extreme between-study homogeneity. STUDY DESIGN: We used
      heterogeneity tests with left-sided statistical significance for inference and
      developed a Monte Carlo simulation test for testing extreme homogeneity in risk
      ratios across studies, using the empiric distribution of the summary risk ratio
      and heterogeneity statistic. A left-sided P=0.01 threshold was set for claiming
      extreme homogeneity to minimize type I error. RESULTS: Among 11,803 meta-analyses
      with binary contrasts from the Cochrane Library, 143 (1.21%) had left-sided P
      value <0.01 for the asymptotic Q statistic and 1,004 (8.50%) had left-sided P
      value <0.10. The frequency of extreme between-study homogeneity did not depend on
      the number of studies in the meta-analyses. We identified examples where extreme
      between-study homogeneity (left-sided P-value <0.01) could result from various
      possibilities beyond chance. These included inappropriate statistical inference
      (asymptotic vs. Monte Carlo), use of a specific effect metric, correlated data or
      stratification using strong predictors of outcome, and biases and potential
      fraud. CONCLUSION: Extreme between-study homogeneity may provide useful insights
      about a meta-analysis and its constituent studies.

PMID- 16980142
TI  - When to use agreement versus reliability measures.
AB  - BACKGROUND: Reproducibility concerns the degree to which repeated measurements
      provide similar results. Agreement parameters assess how close the results of the
      repeated measurements are, by estimating the measurement error in repeated
      measurements. Reliability parameters assess whether study objects, often persons,
      can be distinguished from each other, despite measurement errors. In that case,
      the measurement error is related to the variability between persons.
      Consequently, reliability parameters are highly dependent on the heterogeneity of
      the study sample, while the agreement parameters, based on measurement error, are
      more a pure characteristic of the measurement instrument. METHODS AND RESULTS:
      Using an example of an interrater study, in which different physical therapists
      measure the range of motion of the arm in patients with shoulder complaints, the
      differences and relationships between reliability and agreement parameters for
      continuous variables are illustrated. CONCLUSION: If the research question
      concerns the distinction of persons, reliability parameters are the most
      appropriate. But if the aim is to measure change in health status, which is often
      the case in clinical practice, parameters of agreement are preferred.

PMID- 16980143
TI  - A simple and valid tool distinguished efficacy from effectiveness studies.
AB  - OBJECTIVE: To propose and test a simple instrument based on seven criteria of
      study design to distinguish effectiveness (pragmatic) from efficacy (explanatory)
      trials. STUDY DESIGN: Currently no validated definition of effectiveness studies
      exists. We asked the directors of 12 Evidence-based Practice Centers to select
      six studies each: four that they considered to be examples of effectiveness
      trials and two considered efficacy studies. We then applied our proposed criteria
      to test the construct validity using the selected studies as if they had been
      identified by a gold standard. RESULTS: Based on the rationale to identify
      effectiveness studies reliably with minimal false positives (i.e., a high
      specificity), a cutoff of six criteria produced the most desirable balance
      between sensitivity and specificity. This setting produced a specificity of 0.83
      and a sensitivity of 0.72. CONCLUSION: When applied in a standardized manner, our
      proposed criteria can provide a valid and simple tool to distinguish
      effectiveness from efficacy studies. The applicability of systematic reviews can
      improve when analysts place more emphasis on the generalizability of included
      studies. In addition, clinicians can also use our criteria to determine the
      external validity of individual studies, given an appropriate population of
      interest.

PMID- 16980144
TI  - VEINES-QOL/Sym questionnaire was a reliable and valid disease-specific quality of
      life measure for deep venous thrombosis.
AB  - OBJECTIVE: To assess the validity of VEINES-QOL/Sym, a patient-reported
      questionnaire to evaluate quality of life and symptoms in patients with deep
      venous thrombosis (DVT). STUDY DESIGN AND SETTING: Psychometric study within the
      Venous Thrombosis Outcomes (VETO) Study, a prospective cohort study of long-term
      outcomes after DVT. A total of 359 English- and French-speaking patients with
      acute, objectively diagnosed DVT were recruited at seven hospitals in Quebec,
      Canada. The VEINES-QOL/Sym questionnaire, a 26-item patient-reported measure that
      generates separate summary scores for symptoms (VEINES-Sym) and quality of life
      (VEINES-QOL) was evaluated for acceptability, reliability, validity, and
      responsiveness in VETO Study subjects. RESULTS: Standard psychometric tests
      confirmed the acceptability (missing data, item endorsement frequencies, floor
      and ceiling effects), reliability (internal consistency, item-total and inter
      item correlations, test-retest), validity (content, construct, convergent,
      discriminant, known groups), and responsiveness to clinical change of the VEINES
      QOL/Sym in patients with DVT. CONCLUSION: The VEINES-QOL/Sym is a practical and
      scientifically sound patient-reported measure of outcomes that was developed
      using gold-standard methods. VEINES-QOL/Sym is valid and reliable for use as a
      measure of quality of life and symptoms in patients with acute DVT and provides a
      rigorous tool to allow more comprehensive evaluation of outcomes in clinical
      trials and epidemiological studies of patients with DVT.

PMID- 16980145
TI  - Errors in search strategies were identified by type and frequency.
AB  - OBJECTIVE: Errors in the electronic search strategy of a systematic review may
      undermine the integrity of the evidence base used in the review. We studied the
      frequency and types of errors in reviews published by the Cochrane Collaboration.
      STUDY DESIGN AND SETTING: Data sources were MEDLINE searches from reviews in the
      Cochrane Library, Issue 3, 2002. To be eligible, systematic reviews must have
      been of randomized or quasi-randomized controlled trials, reported included and
      excluded studies, and used one or more sections of the Cochrane Collaboration's
      Highly Sensitive Search Strategy. MEDLINE search strategies not reported in
      enough detail to be assessed or that were duplicates of a search strategy already
      assessed for the study were excluded. Two librarians assessed eligibility and
      scored the eligible electronic search strategies for 11 possible errors. Dual
      review with consensus was used. RESULTS: Of 105 MEDLINE search strategies
      examined, 63 were assessed; 31 were excluded because they were inadequately
      reported, and 11 were duplicates of assessed search strategies. Most (90.5%) of
      the assessed search strategies contained > or =1 errors (median 2, interquartile
      range [IQR] 1.0-3.0). Errors that could potentially lower recall of relevant
      studies were found in 82.5% (median 1, IQR 1.0-2.0) and inconsequential errors
      (to the evidence base) were found in 60.3% (median 1, IQR 0.0-1.0) of the search
      strategies. The most common search errors were missed MeSH terms (44.4%),
      unwarranted explosion of MeSH terms (38.1%), and irrelevant MeSH or free text
      terms (28.6%). Missed spelling variants, combining MeSH and free text terms in
      the same line, and failure to tailor the search strategy for other databases
      occurred with equal frequency (20.6%). Logical operator error occurred in 19.0%
      of searches. CONCLUSION: When the MEDLINE search strategy used in a systematic
      review is reported in enough detail to allow assessment, errors are commonly
      revealed. Additional peer review steps are needed to ensure search quality and
      freedom from errors.

PMID- 16980146
TI  - Causes of death in obesity: relevant increase in cardiovascular but not in all
      cancer mortality.
AB  - BACKGROUND AND OBJECTIVE: To assess the relation between body mass index (BMI)
      and the risk of death from various causes in a prospective cohort study. METHODS:
      In 6,192 obese patients (BMI > or =25 kg/m(2)) with mean BMI 36.6 kg/m(2) (SD
      6.1) and mean age 40.4 years (SD 12.9) who had been referred to the obesity
      clinic of the Heinrich-Heine-University Dusseldorf, Germany, between 1961 and
      1994, there were 1,058 deaths from all causes during a median follow-up time of
      14.8 years. We calculated standardized mortality ratios (SMRs) with 95%
      confidence intervals (CIs) for death from predefined groups of diseases by using
      Germany as reference population. RESULTS: In both sexes, risk of death from
      cardiovascular diseases (men: SMR = 2.2, CI 1.9-2.5; women: SMR = 1.6, CI 1.5
      1.8), from diabetes (men: SMR = 5.4, CI 3.2-8.7; women: SMR = 3.5, CI 2.6-4.8),
      and in men from digestive diseases (SMR = 1.6, CI 1.01-2.3) was significantly
      increased. In contrast to other studies, an association between obesity and all
      cancer mortality could not be found. Only in morbidly obese women (BMI > or =40
      kg/m(2)), all-cancer mortality was significantly increased (SMR = 1.5, CI 1.1
      1.9). CONCLUSION: Obesity is associated with increased risk of death from
      cardiovascular diseases and diabetes in both sexes, and from diseases of the
      digestive system in men.

PMID- 16980147
TI  - In a prospective observational study, influenza vaccination prevented
      hospitalization among older home care patients.
AB  - OBJECTIVE: The aim of the study is (1) to describe the prevalence of vaccination
      against influenza in older home care patients and (2) to investigate the
      protective effect of influenza vaccination for hospitalization events. STUDY
      DESIGN AND SETTING: This is an observational study conducted in four large
      cohorts of elderly patients in home care during the 1998-1999, 1999-2000, 2000
      2001, and 2001-2002 influenza seasons. We analyzed data from the Italian Silver
      Network Home Care project. A total of 2,201 patients were enrolled in the present
      study. The main outcome measures were prevalence of vaccination against influenza
      and the rate of hospitalization according to vaccination status and influenza
      season. RESULTS: The rate of influenza vaccination was around 48% of the studied
      sample. During the follow-up including the peak of influenza and the total
      influenza season, 412 subjects (40%) were hospitalized among vaccinated compared
      to 610 subjects (59%) among not vaccinated (P<0.001). After adjusting for age,
      gender, location of home care program, and all the variables significantly
      different between vaccinated and not-vaccinated subjects, vaccinated subjects
      were less likely to be hospitalized compared to not-vaccinated subjects (OR,
      0.73; 95% CI 0.60-0.90). CONCLUSIONS: Vaccination against influenza has an
      important prognostic implication for frail geriatric patients living in the
      community.

PMID- 16980148
TI  - Racial/ethnic differences in preferences for total knee replacement surgery.
AB  - OBJECTIVES: To determine whether there are ethnic differences in preferences for
      surgery vs. medical treatment of knee osteoarthritis (OA). STUDY DESIGN AND
      SETTING: Cross-sectional in-person interviews using conjoint analysis
      methodology, a technique often used in marketing, involved individuals making
      choices between alternative hypothetical scenarios for medical or surgical
      treatment of knee OA. One hundred ninety-three individuals over the age of 20
      were recruited through random digit dialing in Harris County, TX, and 198
      individuals with knee OA were recruited from a large outpatient health care
      provider in Houston, TX. RESULTS: African Americans were significantly less
      likely to chose surgery than whites (odds ratio 0.63 [0.42, 0.93]). Women and
      older individuals were also less likely to choose surgery (0.69 [0.51, 0.94],
      0.98 [0.97, 0.99]). Larger reductions in negative symptoms with surgery
      significantly increased the likelihood of choosing surgery. There was no
      difference between the public and patients, and no effect of income level.
      CONCLUSIONS: Disparities in knee replacement rates among ethnic groups may be
      partly due to differences in preferences for surgery. Conjoint analysis was shown
      to be a feasible methodology for collecting preferences in health research. This
      methodology has great promise in contributing to our knowledge of drivers of
      health care decision making in individuals.

PMID- 16980149
TI  - Review: a gentle introduction to imputation of missing values.
AB  - In most situations, simple techniques for handling missing data (such as complete
      case analysis, overall mean imputation, and the missing-indicator method) produce
      biased results, whereas imputation techniques yield valid results without
      complicating the analysis once the imputations are carried out. Imputation
      techniques are based on the idea that any subject in a study sample can be
      replaced by a new randomly chosen subject from the same source population.
      Imputation of missing data on a variable is replacing that missing by a value
      that is drawn from an estimate of the distribution of this variable. In single
      imputation, only one estimate is used. In multiple imputation, various estimates
      are used, reflecting the uncertainty in the estimation of this distribution.
      Under the general conditions of so-called missing at random and missing
      completely at random, both single and multiple imputations result in unbiased
      estimates of study associations. But single imputation results in too small
      estimated standard errors, whereas multiple imputation results in correctly
      estimated standard errors and confidence intervals. In this article we explain
      why all this is the case, and use a simple simulation study to demonstrate our
      explanations. We also explain and illustrate why two frequently used methods to
      handle missing data, i.e., overall mean imputation and the missing-indicator
      method, almost always result in biased estimates.

PMID- 16980150
TI  - Using the outcome for imputation of missing predictor values was preferred.
AB  - BACKGROUND AND OBJECTIVE: Epidemiologic studies commonly estimate associations
      between predictors (risk factors) and outcome. Most software automatically
      exclude subjects with missing values. This commonly causes bias because missing
      values seldom occur completely at random (MCAR) but rather selectively based on
      other (observed) variables, missing at random (MAR). Multiple imputation (MI) of
      missing predictor values using all observed information including outcome is
      advocated to deal with selective missing values. This seems a self-fulfilling
      prophecy. METHODS: We tested this hypothesis using data from a study on diagnosis
      of pulmonary embolism. We selected five predictors of pulmonary embolism without
      missing values. Their regression coefficients and standard errors (SEs) estimated
      from the original sample were considered as "true" values. We assigned missing
      values to these predictors--both MCAR and MAR--and repeated this 1,000 times
      using simulations. Per simulation we multiple imputed the missing values without
      and with the outcome, and compared the regression coefficients and SEs to the
      truth. RESULTS: Regression coefficients based on MI including outcome were close
      to the truth. MI without outcome yielded very biased--underestimated-
      coefficients. SEs and coverage of the 90% confidence intervals were not different
      between MI with and without outcome. Results were the same for MCAR and MAR.
      CONCLUSION: For all types of missing values, imputation of missing predictor
      values using the outcome is preferred over imputation without outcome and is no
      self-fulfilling prophecy.

PMID- 16980151
TI  - Imputation of missing values is superior to complete case analysis and the
      missing-indicator method in multivariable diagnostic research: a clinical
      example.
AB  - BACKGROUND AND OBJECTIVES: To illustrate the effects of different methods for
      handling missing data--complete case analysis, missing-indicator method, single
      imputation of unconditional and conditional mean, and multiple imputation (MI)-
      in the context of multivariable diagnostic research aiming to identify potential
      predictors (test results) that independently contribute to the prediction of
      disease presence or absence. METHODS: We used data from 398 subjects from a
      prospective study on the diagnosis of pulmonary embolism. Various diagnostic
      predictors or tests had (varying percentages of) missing values. Per method of
      handling these missing values, we fitted a diagnostic prediction model using
      multivariable logistic regression analysis. RESULTS: The receiver operating
      characteristic curve area for all diagnostic models was above 0.75. The
      predictors in the final models based on the complete case analysis, and after
      using the missing-indicator method, were very different compared to the other
      models. The models based on MI did not differ much from the models derived after
      using single conditional and unconditional mean imputation. CONCLUSION: In
      multivariable diagnostic research complete case analysis and the use of the
      missing-indicator method should be avoided, even when data are missing completely
      at random. MI methods are known to be superior to single imputation methods. For
      our example study, the single imputation methods performed equally well, but this
      was most likely because of the low overall number of missing values.

PMID- 16980152
TI  - Kaplan-Meier methods yielded misleading results in competing risk scenarios.
AB  - BACKGROUND AND OBJECTIVE: Time-to-event curves are routinely presented in the
      medical literature. The most widely used method is the Kaplan-Meier (K-M) method,
      but this analysis approach may not be appropriate when an analysis focuses on
      time-to-first event in scenarios where there are competing events. We compared K
      M methods applying various censoring approaches with the lesser-known "cumulative
      incidence competing risks" (CICR) method in an analysis of competing events.
      METHODS: A registry containing data on 21,624 patients undergoing cardiac
      catheterization was analyzed. Time to coronary artery bypass grafting (CABG) was
      assessed in an analysis for which percutaneous coronary intervention and death
      were competing events. Time-to-CABG curves were calculated using the "K-M censor
      all method," "K-M censor death only method," "K-M ignore all method," and the
      CICR method. RESULTS: One-year CABG rates calculated for the K-M "censor all,"
      "censor death only," and "ignore all" methods were 28.8%, 22.8%, and 22.4%,
      respectively compared to the "actual" rate of 20.8%. For the CICR method, the
      corresponding 1-year rate was identical to the "actual" rate. CONCLUSION: In
      situations with competing risks, and where an analysis focuses on first events,
      the CICR method is most appropriate, as K-M methods will tend to overestimate
      event rates.

PMID- 16980153
TI  - Bias arising from missing data in predictive models.
AB  - OBJECTIVE: The purpose of this study is to determine the effect of three common
      approaches to handling missing data on the results of a predictive model. STUDY
      DESIGN AND SETTING: Monte Carlo simulation study using simulated data was used. A
      baseline logistic regression using complete data was performed to predict
      hospital admission, based on the white blood cell count (WBC) (dichotomized as
      normal or high), presence of fever, or procedures performed (PROC). A series of
      simulations was then performed in which WBC data were deleted for varying
      proportions (15-85%) of patients under various patterns of missingness. Three
      analytic approaches were used: analysis restricted to cases with complete data,
      missing data assumed to be normal (MAN), and use of imputed values. RESULTS: In
      the baseline analysis, all three predictors were all significantly associated
      with admission. Using either the MAN approach or imputation, the odds ratio (OR)
      for WBC was substantially over- or underestimated depending on the missingness
      pattern, and there was considerable bias toward the null in the OR estimates for
      fever. In the CC analyses, OR for WBC was consistently biased toward the null, OR
      for PROC was biased away from the null, and the OR for fever was biased toward or
      away from the null. Estimates for overall model discrimination were substantially
      biased using all analytic approaches. CONCLUSIONS: All three methods of handling
      large amounts of missing data can lead to biased estimates of the OR and of model
      performance in predictive models. Predictor variables that are measured
      inconsistently can affect the validity of such models.

PMID- 16980154
TI  - Are we keeping the secrets to ourselves, or just adopting ideas faster? or, Is
      there a second residency in your future?

PMID- 16980155
TI  - Anesthesiologists are living longer: mortality experience 1992 to 2001.
AB  - STUDY OBJECTIVE: To determine whether there has been any recent change in the
      mortality experience of American anesthesiologists. DESIGN: Retrospective
      analysis of obituary reports to the Physician Master File (PMF) of the American
      Medical Association. MEASUREMENTS: Data were collected from the PMF of
      anesthesiologists and obstetricians. All data were identified from the PMF. A
      total of 1525 obituaries of anesthesiologists and 2773 obituaries of
      obstetricians during the study period, 1992 to 2001, were reviewed. Mean age of
      living or mean age at death of anesthesiologists and obstetricians, as well as
      age-adjusted death rates was calculated. MAIN RESULTS: A gradual increase in age
      at death was noted from 1992 (65.30 +/- 15.61 years) to 2001 (78.13 +/- 12.89
      years) for anesthesiologists (P < 0.005). There was a significant linear decrease
      from 4.3 deaths per thousand to 2.3 deaths per thousand for anesthesiologists in
      this same period. CONCLUSIONS: We observed a significant increase in the average
      age at death and a decreased risk of death among anesthesiologists who died in
      the years 1992 to 2001. Parallel changes were observed in the control population
      of obstetricians.

PMID- 16980156
TI  - Effects of epidural anesthesia with 0.2% and 1% ropivacaine on predicted propofol
      concentrations and bispectral index values at three clinical end points.
AB  - STUDY OBJECTIVE: To compare the effects of 0.2% epidural ropivacaine and those of
      1% epidural ropivacaine on predicted propofol concentrations and bispectral index
      scores (BISs) at three clinical end points. DESIGN: Randomized double-blind
      study. SETTING: University hospital. PATIENTS: Thirty-five (35) ASA physical
      status I and II patients scheduled for elective surgery of the lower abdomen.
      INTERVENTIONS: Patients were randomly divided into 2 groups to receive epidurally
      8 mL of 0.2% or 1% ropivacaine followed by the same solution at a rate of 6 mL/h.
      MEASUREMENTS: Twenty minutes after starting ropivacaine, a target-controlled
      infusion of propofol was started to provide a predicted blood concentration of 3
      microg/mL; it increased by 0.5 microg/mL every 60 seconds until all 3 clinical
      end points were reached, as follows: P1, when patients lost consciousness; P2,
      when patients failed to show pupillary dilation and skin vasomotor reflex to
      transcutaneous electric stimulation applied to the upper level of loss of cold
      sensation; and P3, when patients failed to show pupillary dilation and skin
      vasomotor reflex to transcutaneous electric stimulation applied to C5. MAIN
      RESULTS: The effective concentration 50 values for both predicted blood and
      effect-site propofol concentrations were significantly larger in the 0.2% group
      than in the 1% group at all end points. The BIS at every end point was
      significantly smaller in the 0.2% group than in the 1% group. CONCLUSIONS: During
      combined epidural-propofol anesthesia, unconsciousness and lack of response to
      noxious stimulation occurred at lower predicted concentrations with 1% epidural
      ropivacaine than with 0.2% epidural ropivacaine. The results also suggest that
      the BIS may not be a good indicator when propofol anesthesia is combined with
      epidural anesthesia.

PMID- 16980157
TI  - Postcesarean analgesia: the efficacy of bupivacaine wound instillation with and
      without supplemental diclofenac.
AB  - STUDY OBJECTIVE: To assess the analgesic efficacy of diclofenac when administered
      as an adjuvant to bupivacaine wound instillation. DESIGN: Prospective,
      randomized, double blind, placebo-controlled study. SETTING: Large referral
      hospital. PATIENTS: 90 women recovering from cesarean delivery performed via a
      Pfannenstiel incision. INTERVENTIONS: A standard intrathecal anesthetic was
      administered. On completion of surgery, a multiorifice 20-gauge epidural catheter
      was placed within the surgical wound. Postoperatively, the catheter was attached
      to a patient-controlled analgesia (PCA) device programmed to deliver 9 mL with a
      60-minute lockout time and no basal infusion. In group bupivacaine-diclofenac,
      the PCA device delivered 0.25% bupivacaine, and 20 minutes before the end of
      surgery, patients received intravenous diclofenac (75 mg/100 mL saline).
      Thereafter, oral diclofenac (50 mg) was administered every 8 hours. In group
      bupivacaine-placebo, 0.25% bupivacaine and an equal volume of intravenous saline
      or oral placebo were administered 20 minutes before the end of surgery and every
      8 hours thereafter. In group placebo-diclofenac, wound instillation was with
      sterile water, and 20 minutes before the end of surgery, patients received
      intravenous diclofenac (75 mg/100 mL saline) and thereafter oral diclofenac (50
      mg) at 8-hour intervals. During the first 6 postoperative hours, a coinvestigator
      administered "rescue" morphine (2 mg, intravenously). Thereafter, subcutaneous
      morphine (0.05 mg/kg) was administered on patient request for additional
      analgesia. MEASUREMENTS AND MAIN RESULTS: The number of attempts to activate the
      PCA device was significantly higher in group bupivacaine-placebo (39 +/- 32) when
      compared with group bupivacaine-diclofenac (24 +/- 28). During the first 6
      postoperative hours, the number of patients requiring rescue morphine and the
      total rescue morphine administered were significantly different between the
      groups. During the subsequent 18 hours, subcutaneous morphine administration was
      significantly higher in group bupivacaine-placebo. Postoperative pain scores were
      significantly higher in group bupivacaine-placebo when compared with those
      recorded in groups placebo-diclofenac and bupivacaine-diclofenac. Finally,
      patient satisfaction was significantly lower in group bupivacaine-placebo.
      CONCLUSION: In the context of this study, the bupivacaine wound instillation with
      adjuvant diclofenac administration is associated with similar postoperative
      analgesia to that induced by diclofenac alone.

PMID- 16980158
TI  - Dexmedetomidine infusion is associated with enhanced renal function after
      thoracic surgery.
AB  - STUDY OBJECTIVE: To test the hypothesis that dexmedetomidine, a selective alpha-2
      agonist, enhances urine flow rate and perioperative renal function, a post hoc
      analysis was conducted on a recently completed study of dexmedetomidine used as
      an adjunct to epidural analgesia after thoracotomy. DESIGN: Post hoc analysis of
      a randomized, placebo-controlled, double-blind clinical trial. SETTING: Tertiary
      care university medical center. PATIENTS: 28 patients undergoing elective
      thoracotomy. INTERVENTIONS: Patients were prospectively randomized to receive a
      supplemental 24-hour intravenous infusion of either dexmedetomidine (0.4 microg
      kg(-1) h(-1), n = 14) or saline placebo (equivalent infusion rate, n = 14).
      MEASUREMENTS: Available renal parameters including urine output, calculated
      creatinine clearance (cCl(Cr)), daily serum creatinine level (S(Cr)), and the
      fractional change in S(Cr) level (DeltaS(Cr)%, [peak postoperative S(Cr) -
      baseline S(Cr)] / baseline S(Cr)) x 100) were recorded. MAIN RESULTS: Values are
      expressed as means +/- SD. There were no significant differences in baseline
      values between the groups. The dexmedetomidine group had significantly greater
      cumulative urine output at postoperative hour 4 (473 +/- 35 vs 290 +/- 122 mL, P
      = 0.001) and 12 (1033 +/- 240 vs 822 +/- 234 mL, P = 0.02), although only 14% of
      the group received diuretic agents, compared with 43% in the control group. The
      dexmedetomidine group had significantly better preserved perioperative renal
      function compared with the control group, as assessed by DeltaS(Cr)% (0.04%
      decrease vs 21% increase, P = 0.0007) and cCl(Cr) (75.3 +/- 13.2 vs 62.5 +/- 15.5
      mL/min, P = 0.02). CONCLUSION: Dexmedetomidine infusion administered as a
      supplement to epidural analgesia induced diuresis in postthoracotomy patients
      with normal preoperative renal function and undergoing fluid restriction.
      Although this finding may represent simple reversal of a tubular antidiuresis,
      the lower DeltaS(Cr)% and preservation of cCl(Cr) suggest a beneficial effect on
      glomerular filtration compared with controls.

PMID- 16980159
TI  - Does neuraxial anesthesia reduce intraoperative blood loss? A meta-analysis.
AB  - STUDY OBJECTIVE: To perform a meta-analysis of available randomized controlled
      trials to determine if neuraxial anesthesia would decrease blood loss, compared
      with general anesthesia. DESIGN: Retrospective analysis. SETTING: University
      medical center. MEASUREMENTS: The National Library of Medicine's PubMed database
      was searched from the period of 1966 to December 10, 2003 for all abstracts
      containing words related to neuraxial anesthesia and general anesthesia. The
      search was limited to randomized controlled trials and the English language and
      yielded 667 articles. MAIN RESULTS: A total of 66 articles met inclusion criteria
      and were used for the analysis. Overall, the use of spinal anesthesia resulted in
      significantly less estimated blood loss (EBL) (P < 0.0001), compared with
      epidural anesthesia (EA), which, in turn, resulted in significantly less EBL
      compared with general anesthesia (GA) or combined GA-EA (P < 0.0001). No
      significant difference between GA and GA-EA was noted when analysis was limited
      to studies directly comparing GA-EA and GA. CONCLUSIONS: Use of spinal anesthesia
      or EA is associated with a significant decrease in EBL when compared with that
      for GA or combined GA-EA.

PMID- 16980160
TI  - Transcutaneous monitoring of partial pressure of carbon dioxide in the elderly
      patient: a prospective, clinical comparison with end-tidal monitoring.
AB  - STUDY OBJECTIVE: To evaluate the accuracy and precision of estimation of partial
      pressure of carbon dioxide (Pa(CO2)) using end-tidal or transcutaneous CO2
      (TcP(CO2)) measurements during mechanical ventilation in the elderly patient.
      DESIGN: A prospective, observational study was conducted. SETTINGS: The study was
      done in the anesthesia department of a university hospital. PATIENTS: Seventeen
      anesthetized, mechanically ventilated patients older than 60 years were studied.
      INTERVENTIONS AND MEASUREMENTS: During standard sevoflurane anesthesia, and after
      proper calibration and an equilibration time of 30 minutes with stable
      hemodynamic and respiratory variables, arterial (Pa(CO2)), end-tidal (Pet(CO2)),
      and transcutaneous (TcP(CO2)) CO2 partial pressures were determined. In each
      patient, 1 to 5 sample sets (Pa(CO2), Pet(CO2), and TcP(CO2)) were obtained. MAIN
      RESULTS: A total of 45 sample sets were obtained from the patients studied. The
      Pa(CO2) values ranged between 21 and 58 mm Hg. The Pa(CO2) - Pet(CO2) tension
      gradient was 6 +/- 5 mmHg (95% confidence interval, -3 to 16 mmHg), whereas the
      Pa(CO2) - TcP(CO2) tension gradient was 2 +/- 4 mmHg (95% confidence interval, -6
      to 9 mmHg) (P = 0.0005). The absolute value of the difference between Pa(CO2) and
      Pet(CO2) was 3 mm Hg or less in 7 of 45 sample sets (15%), whereas the absolute
      value of the difference between Pa(CO2) and TcP(CO2) was 3 mm Hg or less in 21 of
      45 sample sets (46%) (P = 0.003). Linear regression analysis for TcP(CO2) versus
      Pa(CO2) showed a slope of 0.84 (r(2) = 0.73), whereas the linear regression
      analysis for Pet(CO2) versus Pa(CO2) showed a slope of 0.54 (r(2) = 0.50).
      CONCLUSION: Transcutaneous monitoring of CO(2) partial pressure gives a more
      accurate estimation of arterial CO(2) partial pressure than does Pet(CO2)
      monitoring.

PMID- 16980161
TI  - Effects of antihypertensive medication on left ventricular function during
      electroconvulsive therapy: study with transthoracic echocardiography.
AB  - STUDY OBJECTIVE: To characterize the effects of antihypertensive medications on
      cardiac function using transthoracic echocardiography during electroconvulsive
      therapy (ECT). STUDY DESIGN: Randomized, double-blind study set at a university
      hospital. PATIENTS: 30 American Society of Anesthesiologists (ASA) physical
      status I and II patients undergoing ECT. INTERVENTIONS: Patients were given
      thiopental sodium (two mg/kg) and succinylcholine (one mg/kg), and mask
      ventilation was initiated with 100% oxygen before bilateral ECT. Patients
      received a bolus injection of one of several different antihypertensive
      medications: 0.08 mg/kg alprenolol, 0.01 mg/kg nitroglycerin, 0.02 mg/kg
      nicardipine, or saline immediately after anesthesia induction and before
      electrical shock. MEASUREMENTS: Cardiac function was examined through
      transthoracic echocardiography before anesthesia induction, throughout the ECT
      procedure, and for 10 minutes after the seizure. MAIN RESULTS: Electrical shock
      resulted in a significant change in fractional area change when compared with the
      awake condition. Further fractional area change at one minute after ECT was
      significantly higher in patients who received nicardipine than in the other
      groups (means +/- SD): control group, 43% +/- 10%; nitroglycerin group, 46% +/-
      8%; nicardipine group, 65% +/- 6% (P < 0.05 vs the other three groups); and
      alprenolol group, 51% +/- 7%. Systolic blood pressure/end-systolic area-end
      diastolic area at one minute after the electrical shock was higher in the
      control, nitroglycerin, and alprenolol groups but not in the nicardipine group
      when compared with the awake condition (means +/- SD): control group, 39 +/- 8
      mmHg/cm(2) (P < 0.05 vs the other three groups); nitroglycerin group, 32 +/- 9
      mmHg/cm(2); nicardipine group, 29 +/- 7 mmHg/cm(2); alprenolol group, 31 +/- 6
      mmHg/cm(2). CONCLUSIONS: Specific antihypertensive drugs produced different
      hemodynamic effects during ECT. Our data suggest that alprenolol was the most
      appropriate agent for minimization of changes in heart rate and transthoracic
      echocardiographic variables after ECT.

PMID- 16980162
TI  - Pneumothorax during argon beam-enhanced coagulation in laparoscopy.
AB  - Argon beam coagulation is an effective modality to control rapid diffuse
      hemorrhage. We present a case of pneumothorax from argon beam coagulation used
      during laparoscopic surgery. We discuss potential cardiopulmonary consequences of
      this relatively new application of argon beam technology.

PMID- 16980163
TI  - An abnormal clinical course of an ultrasound-guided supraclavicular brachial
      plexus block using 0.375% bupivacaine.
AB  - We report on the case of a reappearance of a supraclavicular nerve block after
      the apparent initiation of its resolution in a 21-year-old athlete undergoing
      repair of a valgus impaction syndrome of his right elbow. The patient's
      anesthetic management consisted of a supraclavicular nerve block and general
      anesthesia. The patient was discharged home with an apparent resolving nerve
      block. He returned to the hospital urgently when, at 7 hours after blockade, he
      lost all motor-sensory function in his arm. His workup ultimately yielded
      negative results, and the block resolved at 23 hours. In addition to documenting
      an abnormal course of a supraclavicular block, this case report questions the
      appropriateness of placing long-acting nerve blocks in outpatients.

PMID- 16980164
TI  - Tracheal resection in the morbidly obese patient: the role of dexmedetomidine.
AB  - We present a case of respiratory distress in a morbidly obese woman, which was
      complicated by a severe tracheal stenosis of the third to sixth cartilage. She
      had a history of sleep apnea and could only breathe sitting upright. An
      anesthetic, technique using dexmedetomidine was selected because of its
      properties of anxiolysis and sedation, with lack of respiratory depression. No
      intraoperative or postoperative opioids were required. Dexmedetomidine in high
      doses offers another approach to managing the patient with a compromised airway.
      Opioids were avoided in this patient, who was at major risk of postoperative
      respiratory depression and sleep apnea.

PMID- 16980165
TI  - Anesthesia for cesarean section in a patient with placenta previa and
      methylenetetrahydrofolate reductase deficiency.
AB  - We describe the anesthetic management of a patient with placenta previa
      presenting for a cesarean section, who had methylenetetrahydrofolate reductase
      (MTHFR) deficiency. Methylenetetrahydrofolate reductase deficiency increases
      homocysteine levels in the body and, therefore, predisposes to thrombosis. After
      a cerebrovascular accident at 8 weeks of gestational age, the patient received
      anticoagulants throughout the course of her pregnancy. Bleeding from the placenta
      previa occurred at 30 weeks of gestational age. Although general anesthesia was
      indicated for this patient because of her hemodynamic instability and an
      anticoagulated state, nitrous oxide is contraindicated in such patients. Thus, we
      chose a subarachnoid block because the patient remained hemodynamically stable,
      and anticoagulation had been stopped 8 hours before surgery. To our knowledge,
      there is no reported case of a parturient with MTHFR deficiency complicated with
      a cerebrovascular accident and associated with placenta previa presenting for a
      cesarean section. Anesthetic considerations are discussed in patients presenting
      with placenta previa associated with MTHFR deficiency.

PMID- 16980166
TI  - Airway management during microlaryngoscopic surgery with a Frova airway
      intubation catheter.
AB  - We present a case of microlaryngoscopic surgery for excision of a large vocal
      cord polyp in which a Frova airway intubation catheter, also commonly called a
      Cook's single-use bougie, was used to optimize surgical access. We describe here
      the technique and its advantages.

PMID- 16980167
TI  - Anesthetic challenges in a patient with lymphangioleiomyomatosis complicated by
      myasthenia gravis.
AB  - Lymphangioleiomyomatosis is a rare restrictive lung disease that is often
      associated with pneumothorax and prolonged intubation. We report the successful
      anesthetic management of a patient with lymphangioleiomyomatosis, myasthenia
      gravis, and idiopathic thrombocytopenic purpura undergoing laparoscopic partial
      nephrectomy for renal lesions, and discuss anesthetic management strategies for
      this rare disease process.

PMID- 16980168
TI  - Special doctor's docket. Lethal injection: policy considerations for medicine.

PMID- 16980169
TI  - Independent study and performance on the anesthesiology in-training examination.
AB  - Intuitively, independent study by residents would be expected to improve
      performance on the in-training examination (ITE). So far, however, studies that
      have examined this issue have used historical controls and have not evaluated the
      amount of personal study and its impact on performance. We therefore examined the
      relationship between the amount of self-reported time devoted to personal study
      by 36 clinical anesthesia year 1 and 2 residents at the University of Texas
      Southwestern Medical Center, and their scores on the ITE administered in July
      2003. The average time spent in self-study was 8 +/- 3.6 hours per week, and the
      average scaled score was 28.7 +/- 7.3. Linear regression analysis revealed a
      positive correlation between hours spent in self-study per week and scaled score
      performance on the ITE (correlation coefficient = 0.64, P < 0.0001), where the
      ITE scaled score = (1.3) (hours of self-study per week) + 18.4. Our findings
      emphasize the importance of personal study by residents. In conjunction with our
      diverse clinical and didactic experience, these findings indicate that
      anesthesiology residents who invest a minimum of 10.5 hours of personal study per
      week are well positioned to achieve a passing score on the ITE.

PMID- 16980170
TI  - Anatomical radial artery variation.

PMID- 16980171
TI  - Subarachnoid-cutaneous fistula and subdural hematoma complicating cerebrospinal
      fluid drainage for thoracoabdominal aorta aneurysm repair.

PMID- 16980173
TI  - Morphine sparing with droperidol in patient-controlled analgesia.

PMID- 16980174
TI  - The Magill forceps for removing the intubating laryngeal mask airway after
      tracheal intubation.

PMID- 16980175
TI  - Assessment and management of airway obstruction with tumors.

PMID- 16980176
TI  - Airway examination after nasal packing.

PMID- 16980178
TI  - Hedgehog turns lipoproteins into Janus-faced particles.
AB  - Hedgehog is an important morphogenetic signal during embryonic development. The
      molecule contains several hydrophobic moieties, including cholesterol and
      palmitoyl groups, apparently incompatible with long-range functioning. Very
      recent research, however, performed in the fruitfly Drosophila melanogaster,
      demonstrated that hedgehog can be carried by insect lipoproteins which strongly
      resemble mammalian low-density lipoprotein (LDL), enabling the morphogen to act
      at long distances from its source. Such long-range signaling of hedgehog is in
      perfect agreement with current insight that in mammals hedgehog signaling is not
      terminated after gestation has been completed but remains active throughout life,
      mediating among others revascularization of adult ischemic cardiac tissue. In
      agreement, hedgehog gene therapy is highly effective in experimental rodents for
      limiting the damage after coronary occlusion. If indeed hedgehog is transported
      on lipoproteins in mammals, an interesting change of paradigm might emerge for
      LDL. No longer would LDL merely be bad news for the progression of
      atherosclerotic plaques, as it also conveys a revascularization and tissue
      salvage signal in the form of hedgehog.

PMID- 16980179
TI  - In search of new targets for plasma high-density lipoprotein cholesterol levels:
      promise of human-mouse comparative genomics.
AB  - Many lines of evidence suggest that raising plasma high-density lipoprotein
      cholesterol (HDL-C) levels may inhibit, perhaps even reverse, atherosclerosis.
      Quantitative trait locus (QTL) analysis has been performed in both humans and
      mice. So far, approximately 40 high-density lipoprotein (HDL)-regulating QTLs
      have been identified in each species. To compare human and mouse HDL-C QTLs, we
      generate human-mouse comparative chromosome maps based on homologous genes in
      humans and mice. The comparative maps reveal that most human and mouse HDL-C QTLs
      are concordant, which suggests that identifying the underlying QTL genes in mice
      will facilitate identifying their homologs in humans. The maps also help to
      narrow QTLs by mouse-human homologous QTL comparison. By using a combination of
      classic genetic approaches and newer bioinformatics tools (including comparative
      genomics as highlighted in this study), identifying new drug targets for plasma
      HDL-C levels holds more promise than ever.

PMID- 16980180
TI  - Transcriptional pathways direct cardiac development and regeneration.
AB  - Elegant studies using gene disruption strategies have defined a set of genes that
      are essential for normal cardiac development. Although these studies have
      provided a framework for the molecular regulation of cardiac morphogenesis, the
      genetic program of the cardiac progenitors has been incompletely defined. We used
      a transgenic strategy to specifically target the cardiac progenitors early during
      cardiac morphogenesis. With the use of flow cytometry and transcriptome analysis,
      we comprehensively defined the molecular program of the cardiac progenitors at
      distinct developmental stages. Definition of the molecular cardiac program early
      during development may be useful in the identification of cardiac progenitors
      that are resident in the adult heart. These emerging technologies will be further
      used to define common and distinct regulatory pathways of cardiac progenitors in
      the developing and regenerating heart.

PMID- 16980181
TI  - The role of Smad3-dependent TGF-beta signal in vascular response to injury.
AB  - Transforming growth factor (TGF)-beta is a multifunctional cytokine involved in
      the regulation of proliferation, differentiation, migration, and survival of many
      different cell types. The role of TGF-beta in atherosclerosis has been
      intensively studied, but the precise function of the downstream signals in this
      disease entity remains unclear. We recently discovered that mice lacking Smad3, a
      major downstream mediator of TGF-beta, show enhanced neointimal hyperplasia with
      decreased matrix deposition in response to vascular injury. This review
      summarizes the current view on involvement of TGF-beta in atherosclerotic
      vascular disease and discusses the role of Smad3-dependent TGF-beta signal in
      vascular response to injury.

PMID- 16980182
TI  - Calcium-activated nonselective cation channels in mammalian cardiomyocytes.
AB  - A number of calcium-activated nonselective cation (NSC(Ca)) currents recorded
      from cardiac preparations have been described in the literature. These currents
      are implicated in membrane depolarization and in the modulation of cardiac
      activity. The discovery of a novel family of cation channels, the "transient
      receptor potential" (TRP) protein family, has revived interest in the study of
      nonselective cation channels. In particular, the TRPM4 protein provides the basis
      for an NSC(Ca) channel detected in heart preparations. The role of this channel
      should not be neglected in the description of our understanding of heart activity
      and the development of arrhythmias induced by calcium waves. This review focuses
      on the electrophysiologic and regulatory properties of this native NSC(Ca)
      channel in cardiac preparations compared with those of the TRPM4 protein.
      Physiologic and pathologic implications of the current carried by this channel
      are discussed.

PMID- 16980183
TI  - Phosphoinositide 3-kinase gamma regulates cardiac contractility by locally
      controlling cyclic adenosine monophosphate levels.
AB  - Class I phosphoinositide 3-kinases (PI3Ks) are enzymes with both protein and
      lipid kinase activities that regulate important cellular functions in many
      tissues. In the heart, subclass IA PI3Ks (mainly PI3Kalpha) regulate cell growth,
      apoptosis, cell division and cell size, whereas PI3Kgamma, the only member of
      subclass IB, has been shown to regulate cardiac contractility. We have shown that
      the loss of PI3Kgamma (PI3Kgamma(-/-) mice) enhances cardiac excitation
      contraction coupling by modulating cyclic adenosine monophosphate (cAMP) levels
      in subcellular domains containing the sarcoplasmic reticulum. Specifically,
      PI3Kgamma(-/-) mice show enhanced sarcoplasmic reticulum Ca(2+) cycling in
      association with increased cAMP. Surprisingly, L-type Ca(2+) current, a
      prototypic target of cAMP-dependent protein kinase A phosphorylation, is largely
      unchanged in PI3Kgamma(-/-) mice. In this article, we discuss the consequences
      and implications of cAMP compartmentation in cardiomyocytes. We also review the
      different roles of PI3Kgamma in the heart, particularly as they relate to cardiac
      contractility, intracellular cAMP levels, and the regulation of beta-adrenergic
      receptor signaling in physiologic and pathologic states.

PMID- 16980184
TI  - The medium of signs: nominalism, language and the philosophy of mind in the early
      thought of Dugald Stewart.
AB  - In 1792 Dugald Stewart published Elements of the philosophy of the human mind. In
      its section on abstraction he declared himself to be a nominalist. Although a few
      scholars have made brief reference to this position, no sustained attention has
      been given to the central role that it played within Stewart's early philosophy
      of mind. It is therefore the purpose of this essay to unpack Stewart's nominalism
      and the intellectual context that fostered it. In the first three sections I aver
      that his nominalism emanated from his belief that objects of the mind--qualities,
      ideas and words--were signs that bore no necessary relation to the external
      objects that they were meant to represent. More specifically, it was these signs
      that were arranged into systems of thought by the 'operations of the mind'. The
      next three sections suggest that his treatment of words as signs most probably
      originated in his views on language and medicine and that his nominalistic
      philosophy of mind could also be extended to systems that sought to classify the
      natural world. I conclude by suggesting several avenues of enquiry that could be
      pursued by future scholars interested in excavating Stewart's thought.

PMID- 16980185
TI  - Psychoanalysis as functionalist social science: the legacy of Freud's 'Project
      for a scientific psychology'.
AB  - The paper links Freud's early work in the 'Project for a scientific psychology'
      with the psychoanalytic psychology of Kleinian object relations theory now
      current. Freud is often accused of introducing mechanism into his psychology and
      installing at its core an irreconcilable dichotomy of two disparate ways of
      explaining human behaviour. I suggest that Freud's early mechanistic thinking is
      an attempt at what he only partly achieves, a functional account of the 'mental
      apparatus'. I consider whether this way of conceptualising the mind in functional
      terms is methodologically relevant to psychoanalytic investigation or whether it
      is at best heuristically useful. From a brief consideration of Kleinian object
      relations theory, illustrated by case material, I conclude that there are grounds
      for accepting the first of these alternatives.

PMID- 16980186
TI  - Psychophysics, intensive magnitudes, and the psychometricians' fallacy.
AB  - As an aspiring science in the nineteenth and early twentieth centuries,
      psychology pursued quantification. A problem was that degrees of psychological
      attributes (most importantly, then, intensities of sensations) were experienced
      only as greater than, less than, or equal to one another. They were categorised
      as intensive magnitudes. The meaning of this concept was shifting, from that of
      an attribute possessing underlying quantitative structure (the medieval and
      Kantian meaning) to that of a merely ordinal attribute (its dominant twentieth
      century meaning). This fluidity allowed psychologists to claim that their
      attributes were intensive magnitudes (because ordered) and measurable (because
      intensive magnitudes). This claim was supported by an argument that order entails
      quantity. As adapted by psychometricians, the argument was that if an attribute
      is ordered, then the differences between its degrees are quantitative and,
      therefore, measurable. However, in a paper ignored in psychology for six decades,
      the issue was resolved mathematically and the resolution implies that the
      psychometricians' argument was fallacious.

PMID- 16980187
TI  - Bringing physics to bear on the phenomenon of life: the divergent positions of
      Bohr, Delbruck, and Schrodinger.
AB  - The received view on the contributions of the physics community to the birth of
      molecular biology tends to present the physics community as sharing a basic level
      consensus on how physics should be brought to bear on biology. I argue, however,
      that a close examination of the views of three leading physicists involved in the
      birth of molecular biology, Bohr, Delbruck, and Schrodinger, suggests that there
      existed fundamental disagreements on how physics should be employed to solve
      problems in biology even within the physics community. In particular, I focus on
      how these three figures differed sharply in their assessment of the relevance of
      complementarity, the potential of chemical methods, and the relative importance
      of classical physics. In addition, I assess and develop Roll-Hansen's attempt to
      conceptualize this history in terms of models of scientific change advanced by
      Kuhn and Lakatos. Though neither model is fully successful in explaining the
      divergence of views among these three physicists, I argue that the extent and
      quality of difference in their views help elucidate and extend some themes that
      are left opaque in Kuhn's model.

PMID- 16980188
TI  - 'Your true and proper gender': the Barr body as a good enough science of sex.
AB  - In the late 1940s, a microanatomist from London Ontario, Murray Barr, discovered
      a mark of sex chromosome status in bodily tissues, what came to be known as the
      'Barr body'. This discovery offered an important diagnostic technology to the
      burgeoning clinical science community engaged with the medical interpretation and
      management of sexual anomalies. It seemed to offer a way to identify the true,
      underlying sex in those whose bodies or lives were sexually anomalous
      (intersexuals, homosexuals and transsexuals). The hypothesis that allowed the
      Barr body to stand in for 'chromosomal' or 'genetic' sex was provisional, but it
      supported the expectation that genetic information established one's primary
      identity, and the conviction that the animal world could be neatly divided into
      two, and only two, sexes. Ultimately, this provisional hypothesis, and its status
      as an unambiguous arbiter of true sex, was overturned. But during much of the
      1950s, Barr's thesis about the identity of the Barr body was consistent with a
      coherent set of theories and evidence explaining sexual development and sexual
      pathology. Though provisional, the scientific status of the sex chromatin within
      this system of knowledge was good enough to support a flourishing research
      enterprise in the clinical sciences.

PMID- 16980189
TI  - Block Fitness.
AB  - There are three related criteria that a concept of fitness should be able to
      meet: it should render the principle of natural selection non-tautologous and it
      should be explanatory and predictive. I argue that for fitness to be able to
      fulfill these criteria, it cannot be a property that changes over the course of
      an individual's life. Rather, I introduce a fitness concept--Block Fitness--and
      argue that an individual's genes and environment fix its fitness in such a way
      that each individual's fitness has a fixed value over its lifetime.

PMID- 16980190
TI  - Genetic databases and pharmacogenetics: introduction.
AB  - Since the inception of the Human Genome Project, human genetics has frequently
      been conducted through big science projects, combining academic, state and
      industrial methods, interests and resources. The legitimacy of such projects has
      been linked to national prestige and images of the nation, the purity of
      scientific endeavour, the entrepreneurial spirit, medical progress and the public
      health. A key complication in these discourses is that large-scale genetic
      research has yet to show major results when considered in terms of the objectives
      used to legitimate investment and social support for these projects. The main
      area showing promise at present is the developing field of pharmacogenetics,
      which is now attracting major industry and government investment. Sociological,
      ethical and philosophical study of human genetic sample-based research and
      pharmacogenetics has developed in parallel with inquiry in the biological and
      biomedical sciences. This paper introduces a symposium on the ethical and social
      aspects of this field of biomedical research.

PMID- 16980191
TI  - The consent problem within DNA biobanks.
AB  - Large prospective biobanks are being established containing DNA, lifestyle and
      health information in order to study the relationship between diseases, genes and
      environment. Informed consent is a central component of research ethics
      protection. Disclosure of information about the research is an essential element
      of seeking informed consent. Within biobanks, it is not possible at recruitment
      to describe in detail the information that will subsequently be collected because
      people will not know which disease they will develop. It will also be difficult
      to describe the specific research that will be performed using the biobank, other
      than to stipulate categories of research or diseases that are not included.
      Potential subjects can only be given information about the sorts of research that
      will be performed and by whom. Organisations responsible for biobanks usually
      argue that this disclosure of information is adequate when seeking informed
      consent, especially if coupled with a right to withdraw, as it would not be
      feasible or it would be too expensive to seek consent renewal on a regular basis.
      However, there are concerns about this 'blanket consent' approach'. Consent
      waivers have also been proposed in which research subjects entrust their consent
      with an independent third party to decide whether subsequent research using the
      biobank is consistent with the original consent provided by the subject.

PMID- 16980193
TI  - Pharmacogenetics and uncertainty: implications for policy makers.
AB  - Uncertainty for policy makers is not new but the pressure to make decisions under
      conditions of uncertainty is perhaps greater than ever. The arrival of new
      scientific developments such as pharmacogenetics offers potentially great
      benefits (as well as significant risks). They have passionate supporters as well
      as doubters. The evidence is often extensive but unclear and policy makers may
      find themselves under pressure to make decisions before they feel that the
      evidence is compelling. The UK is particularly well placed to play a leading role
      in the development of pharmacogenetics and is equally well placed to derive the
      benefits to both health and wealth that could flow from this. However, the
      uncertainties threaten to overwhelm the capacity of policy makers to act
      effectively. The uncertainties are both about the context within which the
      science and delivery of pharmacogenetics is being developed and about the
      interests that could be served. This paper maps these uncertainties and concludes
      with some suggestions, drawing on deliberative democracy and futures thinking, as
      to how policy makers might manage the tensions and dilemmas they face by moving
      from an unstable, emergent policy arena to a more stable one.

PMID- 16980192
TI  - Combining efficiency and concerns about integrity when using human biobanks.
AB  - In the debate about human bio-sampling the interests of patients and other sample
      donors are believed to stand against the interests of scientists and of their
      freedom of research. Scientists want efficient access to and use of human
      biological samples. Patients and other donors of blood or tissue materials want
      protection of their integrity. This dichotomy is reflected in the Swedish law on
      biobanks, which came into effect 1 January 2003. In this article I argue that if
      the basic interest of scientists using human biological samples is in increasing
      knowledge and developing better treatments, and if the concept 'integrity' is
      properly understood, then sample donors should also be interested in promotion of
      efficiency as well as in the protection of their integrity. The basic premise of
      this argument is that donors of samples have interests related to the donation
      and use of samples as well as to the use of the results of the research, that is,
      new medical products and treatments. They have a role both as donors or
      participants in research and as end users of the research. I conclude that if (i)
      access to information acquired through biobank research is strictly limited to
      researchers, (ii) the information is protected by secrecy safeguards through
      coding and (iii) the procedures governing the research are open to public and
      democratic control, then most research using human biobanks may be carried out on
      the basis of making general information available when collecting biological
      samples, without further contact with participants.

PMID- 16980194
TI  - Pharmacogenetics: the bioethical problem of DNA investment banking.
AB  - Concern about the ethics of clinical drug trials research on patients and healthy
      volunteers has been the subject of significant ethical analysis and policy
      development--protocols are reviewed by Research Ethics Committees and subjects
      are protected by informed consent procedures. More recently attention has begun
      to be focused on DNA banking for clinical and pharmacogenetics research. It is,
      however, surprising how little attention has been paid to the commercial nature
      of such research, or the unique issues that present when subjects are asked to
      consent to the storage of biological samples. Our contention is that in the
      context of pharmacogenetic add-on studies to clinical drug trials, the doctrine
      of informed consent fails to cover the broader range of social and ethical
      issues. Applying a sociological perspective, we foreground issues of
      patient/subject participation or 'work', the ambiguity of research subject
      altruism, and the divided loyalties facing many physicians conducting clinical
      research. By demonstrating the complexity of patient and physician involvement in
      clinical drug trials, we argue for more comprehensive ethical review and
      oversight that moves beyond reliance on informed consent to incorporate
      understandings of the social, political and cultural elements that underpin the
      diversity of ethical issues arising in the research context.

PMID- 16980195
TI  - Context, ethics and pharmacogenetics.
AB  - Most of the literature on pharmacogenetics assumes that the main problems in
      implementing the technology will be institutional ones (due to funding or
      regulation) and that although it involves genetic testing, the ethical issues
      involved in pharmacogenetics are different from, even less than, 'traditional'
      genetic testing. Very little attention has been paid to how clinicians will
      accept this technology, their attitudes towards it and how it will affect
      clinical practice. This paper presents results from interviews with clinicians
      who are beginning to use pharmacogenetics and explores how they view the ethics
      of pharmacogenetic testing, its use to exclude some patients from treatment, and
      how this kind of testing fits into broader debates around genetics. In particular
      this paper examines the attitudes of breast cancer and Alzheimer's disease
      specialists. The results of these interviews will be compared with the picture of
      pharmacogenetics painted in the published literature, as a way of rooting this
      somewhat speculative writing in clinical practice.

PMID- 16980196
TI  - The promise of pharmacogenetics: assessing the prospects for disease and patient
      stratification.
AB  - Pharmacogenetics is an emerging biotechnology concerned with understanding the
      genetic basis of drug response, and promises to transform the development,
      marketing and prescription of medicines. This paper is concerned with analysing
      the move towards segmented drug markets, which is implicit in the commercial
      development of pharmacogenetics. It is claimed that in future who gets a
      particular drug will be determined by their genetic make up. Drawing on ideas
      from the sociology of expectations we examine how pharmaceutical and
      biotechnology companies are constructing, responding to and realising particular
      'visions' or expectations of pharmacogenetics and market stratification. We argue
      that the process of market segmentation remains uncertain, but that the outcome
      will be fashioned according to the convergence and divergence of the interests of
      key commercial actors. Qualitative data based both on interviews with industry
      executives and company documentation will be used to explore how different groups
      of companies are developing pharmacogenetics in distinct ways, and what
      consequences these different pathways might have for both clinical practice and
      health policy. In particular, the analysis will show a convergence of interests
      between biotechnology and pharmaceutical companies for creating segmented markets
      for new drugs, but a divergence of interest in segmenting established markets.
      Whilst biotechnology firms have a strong incentive to innovate, the
      pharmaceutical industry has no commercial interest in segmenting markets for
      existing products. This has important implications, as many of the claimed public
      health benefits of pharmacogenetics will derive from changing the prescribing of
      existing medicines. One significant implication of this is that biotechnology
      companies who wish to apply pharmacogenetics to existing medicines will have to
      explore an alternative convergence of interests with healthcare payers and
      providers (health insurers, HMOs, MCOs and national health systems). Healthcare
      providers may have a strong incentive to use pharmacogenetics to make the
      prescribing of existing medicine more cost-effective. However, we conclude by
      suggesting that a question mark hangs over their ability to provide the necessary
      economic and structural resources to bring such a vision to fruition.

PMID- 16980198
TI  - Cortisol metabolism in hypertension.
AB  - Corticosteroids are critically involved in blood pressure regulation. Lack of
      adrenal steroids in Addison's disease causes life-threatening hypotension,
      whereas glucocorticoid excess in Cushing's syndrome invariably results in high
      blood pressure. At a pre-receptor level, glucocorticoid action is modulated by
      11beta-hydroxysteroid dehydrogenases (11beta-HSDs). 11Beta-HSD1 activates
      cortisone to cortisol to facilitate glucocorticoid receptor (GR)-mediated action.
      By contrast, 11beta-HSD2 plays a pivotal role in aldosterone target tissues where
      it catalyses the opposite reaction (i.e. inactivation of cortisol to cortisone)
      to prevent activation of the mineralocorticoid receptor (MR) by cortisol.
      Mutations in the 11beta-HSD2 gene cause a rare form of inherited hypertension,
      the syndrome of apparent mineralocorticoid excess (AME), in which cortisol
      activates the MR resulting in severe hypertension and hypokalemia. Ingestion of
      competitive inhibitors of 11beta-HSD2 such as liquorice and carbenoxolone result
      in a similar but milder clinical phenotype. Epidemiological data suggests that
      polymorphic variability in the HSD11B2 gene determines salt sensitivity in the
      general population, which is a key predisposing factor to adult onset
      hypertension in some patients. Extrarenal sites of glucocorticoid action and
      metabolism that might impact on blood pressure include the vasculature and the
      central nervous system. Intriguingly, increased exposure to glucocorticoids
      during fetal life promotes high blood pressure in adulthood suggesting an early
      programming effect. Thus, metabolism and action in many peripheral tissues might
      contribute to the pathophysiology of human hypertension.

PMID- 16980199
TI  - Insulin resistance in hypertension and cardiovascular disease.
AB  - Insulin resistance is not simply a problem of decreased glucose uptake in
      response to insulin, but a multifaceted syndrome that significantly increases the
      risk for cardiovascular disease. Insulin resistance is strongly associated with
      arterial hypertension and a pathogenetic role in the development of arterial
      hypertension has been suggested. One question that remains open concerns the
      clinical approach to insulin-resistant patients. Observational and clinical trial
      data suggest that lifestyle changes including weight reduction and regular
      physical activity can improve insulin sensitivity and reduce the incidence and
      mortality of cardiovascular disease. Daily physical activity of moderate
      intensity for 30 min has a cardioprotective effect and reduces insulin
      resistance, independent of the effect on body weight. A pharmacological therapy
      for insulin resistance reducing cardiovascular disease remains to be defined.
      Concerning the antihypertensive therapy of insulin-resistant hypertensive
      patients, most hypertensive guidelines fail to provide specific advice.

PMID- 16980200
TI  - Screening for primary aldosteronism.
AB  - Normokalaemic manifestation of primary aldosteronism is a frequent cause of
      secondary hypertension. It occurs in approximately 5-12% of all patients with
      hypertension, primarily patients with severe and uncontrolled blood pressure.
      Main causes are bilateral adrenal hyperplasia (2/3 of cases) and aldosterone
      producing adenoma (1/3 of cases). Screening is performed by measurement of the
      aldosterone/renin ratio, which is raised in affected patients. Suspicion of
      primary aldosteronism due to a pathological ratio requires confirmatory testing
      e.g. by saline infusion test or fludrocortisone suppression test. If the
      diagnosis is confirmed, the underlying cause of aldosterone excess needs to be
      identified because therapy differs. First, adrenal imaging (CT/MRI) is performed,
      which is followed by postural testing in cases with a unilateral lesion.
      Concordant results confirm the diagnosis of an aldosterone-producing adenoma and
      allow treatment to proceed to adrenalectomy. In cases of equivocal results or
      normal/bilaterally enlarged adrenal glands on imaging, adrenal venous sampling
      must be performed for subtype differentiation.

PMID- 16980201
TI  - Surgically correctable hypertension caused by primary aldosteronism.
AB  - Surgically correctable forms of primary aldosteronism are generally held to be
      less common than forms requiring medical therapy. However, with the availability
      of improved diagnostic techniques and the adoption of a systematic and thorough
      diagnostic work-up they can be identified more commonly than expected. Adrenal
      vein sampling (AVS) for measurement of cortisol and aldosterone has emerged as
      the 'gold standard' diagnostic test for identifying unilateral causes of primary
      aldosteronism that are amenable to surgical cure. Adrenalectomy can provide long
      term normalisation of blood pressure and correction of primary aldosteronism in
      about 55% of patients with an aldosterone-producing adenoma and can markedly
      ameliorate blood pressure control in the rest. This chapter summarises the
      diagnostic work-up suggested for identifying these forms and examines the other
      diseases mimicking mineralocorticoid excess that enter into the differential
      diagnosis of surgically curable primary aldosteronism.

PMID- 16980202
TI  - Monogenic mineralocorticoid hypertension.
AB  - Monogenic mutations leading to excessive activation of the mineralocorticoid
      pathway result, almost always, in suppressed renin and hypertension in adult life
      and sometimes in hypokalaemia and alkalosis, which can be severe. In most of
      these syndromes, precise molecular changes in specific steroidogenic or effector
      genes have been identified, permitting appreciation of (1) pathophysiology, (2)
      great diversity of phenotype and (3) possibility of genetic methods of diagnosis.
      Yet to be achieved elucidation of the genetic basis of familial
      hyperaldosteronism type II, the most common and clinically significant of them,
      will enhance detection of primary aldosteronism, currently the commonest
      specifically treatable and potentially curable form of hypertension. While
      classic, complete-phenotype presentations of monogenic forms of mineralocorticoid
      hypertension are rarely recognised, more subtle genetic expression causing less
      florid manifestations could represent a significant proportion of so-called
      'essential hypertension.'

PMID- 16980203
TI  - Initial work-up and long-term follow-up in patients with phaeochromocytomas and
      paragangliomas.
AB  - Catecholamine-producing tumours may arise in the adrenal medulla
      (phaeochromocytomas) or in extra-adrenal chromaffin cells (paragangliomas). The
      most specific and sensitive diagnostic test is the determination of plasma or
      urinary metanephrine levels. The tumour can be located by computed tomography,
      magnetic resonance imaging and metaiodo-benzylguanidine scintigraphy. Patients
      are treated by tumour resection. Phaeochromocytomas and paragangliomas may be
      sporadic or the result of several genetic diseases: multiple endocrine neoplasia
      type 2, neurofibromatosis 1, von Hippel-Lindau disease, succinate dehydrogenase
      phaeochromocytoma-paraganglioma syndrome. Familial cases are diagnosed earlier
      and are more frequently bilateral and recurrent than sporadic cases. About 10% of
      tumours are malignant, either at initial surgery or during follow-up. Recurrences
      and malignancy are more frequent in cases with large or extra-adrenal tumours and
      in the succinate dehydrogenase subunit B-related phaeochromocytoma-paraganglioma
      syndrome. Patients should be followed up indefinitely, particularly if they have
      familial or extra-adrenal tumours.

PMID- 16980204
TI  - Genetic basis of phaeochromocytoma and paraganglioma.
AB  - Advances in the knowledge of the genetics of phaeochromocytoma have broadened our
      understanding about the mechanisms of tumorigenesis. Formerly it was believed
      that 10% of phaeochromocytomas were associated with familial cancer syndromes,
      but it is now recognised that up to 30% of these tumours may be familial. In
      particular, attention has been focused on those patients with apparently sporadic
      presentations where 12-24% of patients have been shown to carry germline
      mutations indicating hereditary disease. Consideration of genetic testing is now
      recommended for all apparently sporadic cases and, following the identification
      of a mutation-positive carrier, the offering of genetic testing to first degree
      relatives. There is a need for lifelong follow up of affected individuals and
      asymptomatic mutation-positive carriers, but validation of screening protocols
      has yet to be determined.

PMID- 16980205
TI  - Incidentally discovered masses in hypertensive patients.
AB  - Endocrine hypertension is a term used for states in which hormone derangements
      result in clinically significant hypertension. The adrenal glands are the most
      likely culprits, due either to an excessive production of mineralocorticoids,
      catecholamines or glucocorticoids. The term 'adrenal incidentaloma' indicates an
      adrenal mass discovered accidentally during testing or treatment for other
      clinical conditions unrelated to any suspicion of adrenal disease. In particular,
      when an adrenal mass is discovered in a hypertensive subject, physicians must
      check whether the patient has pheochromocytoma, glucocorticoid excess or primary
      aldosteronism. Although most adrenal masses are non-hypersecretory adenomas,
      hormone screening can reveal a significant number of cases of clinically
      unsuspected hormone-secreting adrenal tumors. If the clinical history or physical
      examination of a patient with unilateral incidentaloma shows signs and symptoms
      suggestive of glucocorticoid, mineralocorticoid, adrenal sex hormone or
      catecholamine excess, which is confirmed biochemically, the treatment of choice
      is often adrenalectomy. In cases where surgery is contraindicated or the lesions
      are unresectable, medical treatment may be an option.

PMID- 16980206
TI  - Hypertension in Cushing's syndrome.
AB  - Cushing's syndrome can be exogenous, resulting from the administration of
      glucocorticoids or adrenocorticotrophic hormone (ACTH), or endogenous, secondary
      to increased secretion of cortisol or ACTH. Hypertension is one of the most
      distinguishing features of endogenous Cushing's syndrome, as it is present in
      about 80% of adult patients and in almost half of children and adolescents
      patients. Hypertension results from the interplay of several pathophysiological
      mechanisms regulating plasma volume, peripheral vascular resistance and cardiac
      output, all of which may be increased. The therapeutic goal is to find and remove
      the cause of excess glucocorticoids, which, in most cases of endogenous Cushing's
      syndrome, is achieved surgically. Treatment of Cushing's syndrome usually results
      in resolution or amelioration of hypertension. However, some patients may not
      achieve normotension or may require a prolonged period of time for the correction
      of hypercortisolism. Therefore, therapeutic strategies for Cushing's-specific
      hypertension (to normalise blood pressure and decrease the duration of
      hypertension) are necessary to decrease the morbidity and mortality associated
      with this disorder. The various pathogenetic mechanisms that have been proposed
      for the development of glucocorticoid-induced hypertension in Cushing's syndrome
      and its management are discussed.

PMID- 16980207
TI  - Laparoscopic adrenalectomy.
AB  - Laparoscopic adrenalectomy (LA) was first described in the literature in 1992,
      and has become the preferred method for the removal of benign functioning and non
      functioning tumors of the adrenal gland <12 cm. The objectives of the present
      study are to review the experience of LA gained since it was first done in 1992
      and to critically evaluate its effectiveness for the surgical management of
      endocrine hypertension; specifically pheochromocytoma, aldosteronoma and
      Cushing's syndrome and disease, as opposed to open adrenalectomy. The benefits of
      minimally invasive techniques for the removal of the adrenal gland include
      decreased requirements for analgesics, improved patient satisfaction, shorter
      hospital stay and recovery time when compared to open surgery. LA can be
      performed safely for bilateral disease and may become the standard of care for
      malignant tumors. Current limitations are operator-dependent and not a factor of
      limitations of minimally invasive techniques. A thorough pre-operative work-up is
      key for differentiating the various cases of hypertension and adequate pre
      operative treatment is paramount when indicated.

PMID- 16980209
TI  - Contemporary concepts of inflammation, damage and repair in rheumatic diseases.
AB  - Chronic arthritis has been regarded as a disease resulting from a disequilibrium
      in pro- and anti-inflammatory cytokines. Restoration of this imbalance by using
      blocking antibodies or soluble receptors against a variety of inflammatory
      components has been the focus of most therapeutic interventions so far. More
      recently, other destructive mechanisms partially independent of inflammation have
      been elucidated, including osteoclast mediated bone resorption driven by the
      RANKL/RANK system. Despite efficient control of inflammation and destruction,
      little joint tissue repair has been observed. In addition, abnormal tissue
      responses such as cartilage calcification and ankylosis may contribute to disease
      progression and loss of joint function. We propose that 'true' disease remission
      may only be achieved with appropriate activation of local joint tissue responses
      leading to restoration of joint homeostasis and recovery of joint function.
      Understanding the molecular networks of joint homeostasis, repair and remodelling
      will be required to achieve this goal. Defining and validating clinical outcomes
      evaluating remission remain a challenge.

PMID- 16980211
TI  - New cytokine targets in inflammatory rheumatic diseases.
AB  - With the advent of biological therapies, considerable advances have been achieved
      in the treatment of inflammatory arthritis. These have arisen primarily from
      studies elucidating mechanisms of pathophysiology and are best exemplified in the
      wide use of tumour necrosis factor (TNF) blockade in several rheumatic diseases.
      The identification of additional pro-inflammatory factors in rheumatic diseases
      and an understanding of their effector function, now offers major possibilities
      for the generation of novel therapeutics. To address unmet clinical need, such
      interventions will ideally fulfil several of the following criteria: (1) control
      of inflammation, (2) modulation of underlying immune dysfunction - promoting the
      re-establishment of immune tolerance, (3) protection of targeted tissues such as
      bone and cartilage - this should encompass promoting healing of previously
      damaged tissues, (4) preservation of host immune capability - to avoid profound
      immune suppression and (5) amelioration of co-morbidity associated with
      underlying inflammatory arthritis. This short review will consider those novel
      cytokine activities that represent optimal utility as therapeutic targets. Since
      we wish to reflect the current predominant research effort, we will focus
      primarily on rheumatoid arthritis (RA) based studies.

PMID- 16980210
TI  - Treating very early rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is common and leads to joint damage due to persistent
      synovitis. The persistence of inflammation is maintained by hyperplastic stromal
      tissue, which drives the accumulation of leukocytes in the synovium. Aggressive
      treatment after the first 3-4 months of symptoms, with either disease modifying
      anti-rheumatic drugs or anti-tumor necrosis factor (TNF)-alpha therapy, reduces
      the rate of disease progression. However, it rarely switches off disease such
      that remission can be maintained without the continued need for immunosuppressive
      therapy. There is increasing evidence that the first few months after symptom
      onset represent a pathologically distinct phase of disease. This very early phase
      may translate into a therapeutic window of opportunity during which it may be
      possible to permanently switch off the disease process. The rationale for, and
      approaches to, treatment within this very early window are discussed.

PMID- 16980212
TI  - Is IL-1 a good therapeutic target in the treatment of arthritis?
AB  - Inflammation is an important homeostatic mechanism that limits the effects of
      infectious agents. However, inflammation might be self-damaging and therefore has
      to be tightly controlled or even abolished by the organism. Interleukin 1 (IL-1)
      is a crucial mediator of the inflammatory response, playing an important part in
      the body's natural responses and the development of pathological conditions
      leading to chronic inflammation. While IL-1 production may be decreased or its
      effects limited by so-called anti-inflammatory cytokines, in vitro IL-1
      inflammatory effects are inhibited and can be abolished by one particularly
      powerful inhibitor, IL-1 receptor antagonist (IL-1Ra). Recent research has shown
      that in the processes of rheumatoid arthritis (RA) IL-1 is one of the pivotal
      cytokines in initiating disease, and IL-1Ra has been shown conclusively to block
      its effects. In laboratory and animal studies the inhibition of IL-1 by either
      antibodies to IL-1 or IL-1Ra proved beneficial to the outcome. Because of its
      beneficial effects in many animal disease models, IL-1Ra has been used as a
      therapeutic agent in human patients. The recombinant form of IL-1Ra, anakinra
      (Kineret, Amgen) failed to show beneficial effects in septic shock and displays
      weak effects in RA patients. However, IL-1 blockade by anakinra is dramatically
      effective in systemic-onset juvenile idiopathic arthritis, in adult Still's
      disease and in several autoinflammatory disorders, most of the latter being
      caused by mutations of proteins controlling IL-1beta secretion. Importantly, to
      be efficacious, anakinra required daily injections, suggesting that administered
      IL-1Ra displays very short-term effects. Better IL-1 antagonists are in the
      process of being developed.

PMID- 16980213
TI  - Diversity of regulatory T cells to control arthritis.
AB  - During follow-up of the suppressive functions of CD4+ T helper (Th) 2 cells in
      recent years, the suppressive capacities of newly recognised CD4+ Th cells with
      more widespread suppressive potential have been extensively investigated. These
      Th cells, collectively termed regulatory T cells, are characterised by the
      secretion of specific cytokines, such as interleukin (IL)-10 (Tr1 Th cells),
      transforming growth factor (TGF)beta (Th3 cells) or the constitutive expression
      of CD25 (naturally occurring T regulatory cells, nTregs). The balance of these
      regulatory T cells with pro-inflammatory effector T cells, such as Th1
      (interferon (IFN)gamma secreting), Th17 (IL-17 secreting) and CD25- Th cells, has
      been shown to be of pivotal importance for the development and persistence of
      autoimmune diseases. The high potential of regulatory T cells (in particular
      nTregs), to efficiently suppress several arthritic responses both in humans and
      in animal models of arthritis, make them therapeutic targets of interest in
      arthritic conditions such as rheumatoid arthritis.

PMID- 16980214
TI  - B cell depletion therapy in rheumatic disease.
AB  - B cell depletion therapy was introduced for auto-antibody associated rheumatic
      disease in 1998. Encouraging pilot studies in rheumatoid arthritis were followed
      by randomised controlled trials confirming major benefit. Licensing for use in
      patients unable to benefit from tumour necrosis factor alpha (TNFalpha)
      neutralising agents is envisaged shortly. Open studies in other disorders, in
      particular systemic lupus erythematosus (SLE), have also suggested benefit and
      its use in life-threatening situations is becoming widespread. Toxicity appears
      to compare favourably with other agents, but respiratory problems may be more
      common. Repeated therapy is effective, but may lead to hypogammaglobulinemia.
      Rituximab is currently the main agent used but other agents are in development.
      Optimal protocols are not well characterised and will probably be different for
      different conditions.

PMID- 16980215
TI  - Chemokine inhibition in inflammatory arthritis.
AB  - Synovial inflammation in rheumatoid arthritis (RA) and other arthritides is, in
      part, dependent on migration of inflammatory cells as well as retention of these
      cells at the site of inflammation. Chemokines play a critical role in these
      processes and represent an attractive target for therapeutic intervention. Animal
      models of RA have shown that it is possible to induce clinical improvement by
      specifically targeting chemokines or their receptors. Although at present only
      very limited data exist, initial data suggest that it may be possible to reduce
      synovial inflammation in patients with RA by specific chemokine blockade.
      Innovative trial design may help to screen for potentially interesting chemokine
      antagonists in an early stage of development.

PMID- 16980216
TI  - Inhibition of angiogenic pathways in rheumatoid arthritis: potential for
      therapeutic targeting.
AB  - Angiogenesis is a significant and possibly primary event in the pathogenesis of
      inflammatory diseases including arthritis. Abnormalities of vascular morphology
      and angiogenesis have been described at the macroscopic, histological and
      molecular levels in the synovial membrane in rheumatoid, seronegative and
      degenerative arthritis. The vascular endothelium is an active organ that
      participates in the initiation and maintenance of the inflammatory response.
      Endothelial cells (EC) are activated by a variety of stimuli to express surface
      adhesion molecules to bind and facilitate, via an active process, the movement of
      white blood cells such as neutrophils, macrophages and lymphocytes into the
      target tissue. The main stimuli known to activate EC and initiate angiogenesis
      include hypoxia, inflammatory mediators and mechanical stress. Irrespective of
      the trigger a series of messages, such as cytokine release, production of growth
      factors and subsequent downstream molecular messages, result in changes to vessel
      permeability, EC proliferation and migration, disruption of the basement membrane
      and formation of new vascular tubes. Several key growth factors are known to
      upregulate EC activation and proliferation leading to the sprouting of new
      vessels that then stabilise and mature, recruiting smooth muscle pericytes to
      consolidate vessel wall structure. In this review the process of angiogenesis in
      the arthritic joint, including the stimuli and molecular pathways will be
      discussed and potential therapeutic targeting of critical steps will be
      highlighted.

PMID- 16980217
TI  - Spondyloarthropathy: disease at the crossroads of immunity.
AB  - Up until recently, the prevailing paradigm relating to spondyloarthropathy (SpA)
      pathogenesis was that they were human leukocyte antigen (HLA)-associated, T-cell
      driven autoimmune diseases. This view is now being questioned. Careful studies of
      well-characterised cohorts of patients with SpA, including detailed analysis of
      involved tissue, together with clinical trials of targeted treatments, in
      particular anti-tumour necrosis factor (TNF) therapies, have contributed
      enormously to both interest in and understanding of disease pathogenesis. In this
      chapter, our current knowledge and understanding of the relative contributions of
      the components of the innate and adaptive arms of the immune response to SpA
      pathogenesis is reviewed. It is clear that both arms of the immune response are
      involved and inter-dependent in SpA. With continued emphasis on discovery
      research, including detailed analysis of novel therapeutic interventions,
      significant additional breakthroughs in SpA are likely to be forthcoming.

PMID- 16980218
TI  - The role of mesenchymal cells in the pathophysiology of inflammatory arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disorder of the joints that
      can cause severe disability. While the role of inflammatory cells in the
      pathogenesis of RA has been well established, the specific contribution of
      resident cells within the synovial membrane, especially those of mesenchymal
      origin, has become the object of closer scrutiny only recently. The central
      position of these cells in the disease process of RA is underlined by their
      involvement in its main pathophysiological features: inflammation, hyperplasia
      and joint destruction. In this chapter, we provide a characterisation of resident
      mesenchymal cells, specifically fibroblast-like cells in the rheumatoid synovium,
      and give an overview of the molecular pathways by which these cells are involved
      in the initiation and perpetuation of RA.

PMID- 16980219
TI  - Understanding the role of tissue degrading enzymes and their inhibitors in
      development and disease.
AB  - Cartilage and the underlying bone are destroyed in severe cases of arthritis
      preventing joints from functioning normally. Cartilage and bone collagen can be
      specifically cleaved by the collagenases, members of the matrix metalloproteinase
      family (MMPs), whilst cartilage aggrecan is degraded by members of the ADAMTS (A
      Disintegrin And Metalloproteinase with ThromboSpondin repeats) family of
      proteinases. Intracellular cysteine proteinases are involved in bone resorption
      by osteoclasts and the serine proteinases are involved in activating MMPs.
      Together, these enzymes act in concert during normal growth and development,
      especially within the growth plate; however they are also involved in tissue
      destruction during disease. Synthetic MMP inhibitors have been investigated as a
      means to block tissue destruction in arthritis but have been unsuccessful,
      although recent trials with doxycycline suggest this may block joint destruction
      in osteoarthritis. It is likely that combinations of therapy will be required to
      ensure that joint destruction is prevented in arthritis patients.

PMID- 16980220
TI  - Update on the biology of the chondrocyte and new approaches to treating cartilage
      diseases.
AB  - Osteoarthritis (OA) is a joint disease that involves degeneration of articular
      cartilage, limited intraarticular inflammation manifested by synovitis and
      changes in the subchondral bone. The aetiology of OA is largely unknown, but
      since it may involve multiple factors, including mechanical, biochemical and
      genetic factors, it has been difficult to identify unique targets for therapy.
      Chondrocytes, which are the unique cellular component of adult articular
      cartilage, are capable of responding to structural changes in the surrounding
      cartilage matrix. Since the initial stages of OA involve increased cell
      proliferation and synthesis of matrix proteins, proteinases and cytokines in the
      cartilage, laboratory investigations have focused on the chondrocyte as a target
      for therapeutic intervention. The capacity of the adult articular chondrocyte to
      regenerate the normal cartilage matrix architecture is limited, however, and the
      damage becomes irreversible unless the destructive process is interrupted.
      Current pharmacological interventions that address chronic pain are insufficient
      and no proven disease-modifying therapy is available. Identification of methods
      for early diagnosis is of key importance, since therapeutic interventions aimed
      at blocking or reversing structural damage will be more effective when there is
      the possibility of preserving normal homeostasis. At later stages, cartilage
      tissue engineering with or without gene therapy with anabolic factors will also
      require therapy to inhibit inflammation and block damage to newly repaired
      cartilage. This review will focus on experimental approaches currently under
      study that may lead to elucidation of effective strategies for therapy in OA,
      with emphasis on mediators that affect the function of chondrocytes and
      interactions with surrounding tissues.

PMID- 16980223
TI  - [Basic cancer research in Quebec].
AB  - Recent establishments and development of several institutes dedicated to cancer
      research in Quebec has dramatically improved the scientific infrastructures and
      the quality of basic and clinical programs in this province. A recent study
      performed by the Fonds de recherche en sante du Quebec (FRSQ), estimates that
      oncology research output by impact factors and number of publications from Quebec
      universities and hospital based institutes is the most performing field of
      biomedical research in the province. Direct and growing collaborations between
      these centres and their usage of state of the art technological platforms place
      them in an excellent position to participate into first-rate oncology studies on
      the international scene.

PMID- 16980224
TI  - [The reseau de recherche sur le cancer: favoring a multi-disciplinary approach].
AB  - The Reseau de recherche sur le cancer (RR-cancer) a unit of the Fonds de la
      recherche en sante du Quebec (FRSQ) has joined the worldwide effort to uncover
      mechanisms involved in cancer development through its well established clinical
      and fundamental research units. Encouraged by the excellence of the Quebec
      research community, the RR-cancer has developed a specialized infrastructure
      which allows better access to tissues and to state of the art analysis services.
      The research is founded on four axes: 1) Database and Tissue Bank; 2) Leukaemia
      cell bank; 3) Experimental therapy and 4) the Oncological Research Group of
      Quebec. With these programs, the RR-cancer contributes to ameliorating
      prevention, diagnosis and treatment of cancer by facilitating access to the
      highest quality research material. Optimization of resources is made possible by
      the contributions of basic scientists and clinicians working together towards a
      unified objective: fighting cancer.

PMID- 16980225
TI  - [Governing the fight against cancer in Quebec].

PMID- 16980226
TI  - [The limited spectrum of pathogenic BRCA1 and BRCA2 mutations in the French
      Canadian breast and breast-ovarian cancer families, a founder population of
      Quebec, Canada].
AB  - The unique genetic demography of the French Canadian population of Quebec,
      Canada, has provided a means to study the contribution of BRCA1 and BRCA2, the
      breast-ovarian cancer susceptibility genes. Here we review BRCA1 and BRCA2 in the
      context of French Canadian cancer families, a well-characterized founder
      population known for its contributions to medical genetics. Pathogenic BRCA1 and
      BRCA2 mutations contribute to a significant proportion of hereditary breast
      and/or ovarian cancer families of French Canadian descent. BRCA1 and BRCA2
      mutations have been reported in approximately 40 % of families with at least
      three cases of breast and/or ovarian cancer, where breast cancer diagnosis
      occurred before age 66 years, and where all cases occurred within first-, second-
      and/or third-degree relatives to index affected cases tested for mutations. The
      proportion of mutation-positive families was very similar to that reported in
      independent studies of families not selected for ethnicity. However, 84 % of
      mutation-positive families were accounted for by one of eight pathogenic
      mutations in BRCA1 (2953delGTA + C, 3875delGTCT, and 4446C --> T) and BRCA2
      (2816insA, 3398delAAAAG, 6085G --> T, 6503delTT, and 8765delAG). Haplotype
      analyses has suggested that carriers of the most common recurring mutations share
      a related ancestry. This effect has been attributed to common founders in the
      French Canadian population of Quebec who emigrated from France in between 1608
      and 1759. It is possible that novel highly penetrant cancer susceptibility genes
      account for a fraction of the 60 % of BRCA mutation-negative French Canadian
      cancer families. The continued genetic analysis and phenotypic characterization
      of French Canadian cancer families is warranted given the large family structure
      of these families are amenable for classical genome-wide linkage analysis for
      novel breast and ovarian cancer susceptibility genes.

PMID- 16980227
TI  - [Breast density: a biomarker to better understand and prevent breast cancer].
AB  - In Quebec, cancer is the principal cause of mortality. This epidemiologic
      research program includes two components. The first component takes place at the
      "Institut national de sante publique du Quebec" and involves surveillance and
      evaluation of practices in oncology with the aim of providing the Quebec Ministry
      of Health with some of the evidence needed to determine its policies in cancer
      control. The second component takes place at the "Unite de recherche en sante des
      populations (URESP)" of Laval University and is devoted to studying the etiology
      and prevention of breast cancer. This paper focuses on this second research
      component which uses mammographic breast density as an intermediate biomarker to
      study the causes of breast cancer and strategies to prevent it. Breast cancer
      risk is much higher among women with very dense breasts than among those with
      little or no breast density. Recently, we were among the first to show that women
      with high vitamin D or calcium intakes have less breast density than those with
      low intakes, especially among premenopausal women. Furthermore, we have confirmed
      that breast density was increased among premenopausal women with high levels of
      IGF-I and low levels of IGFBP3 which is consistent with the observed effect of
      these molecules on breast cancer risk. Studies are now being conducted to assess
      whether breast density varies according to blood levels of vitamin D and of
      additional growth factors, as well as to genetic polymorphisms involved in the
      pathways of vitamin D, calcium and growth factors. The increase in vitamin D and
      calcium intakes may prove to be a safe and inexpensive approach to breast cancer
      prevention; this possibility should be carefully examined as quickly as possible.

PMID- 16980228
TI  - [Genetic determinants of childhood leukemia].
AB  - Pediatric cancers affect approximately 1 in every 500 children before the age of
      15. Little is known about the etiology of this heterogeneous group of diseases
      despite the fact they constitute the major cause of death by disease among this
      population. Because of its relatively high prevalence, most of the work done in
      pediatric oncogenetics has been focused on leukemias, particularly acute
      lymphoblastic leukemia (ALL). Although it is now well accepted that genetic
      variations play a significant role in determining individual's cancer
      susceptibility, few studies have explored genetic susceptibility to childhood
      leukemia with respect to common polymorphisms. The biochemical and genetic
      mechanisms contributing to cancer susceptibility are numerous and can be grouped
      into broad categories: 1) cellular growth and differentiation, 2) DNA replication
      and repair, 3) metabolism of carcinogens, 4) apoptosis, 5) oxidative stress
      response and 6) cell cycle. To evaluate whether candidate genes in these pathways
      are involved in childhood leukemogenesis, we conducted association studies. We
      showed that leukemogenesis in children may be associated with DNA variants in
      some of these genes and that the combination of genotypes seems to be more
      predictive of risk then either of them independently. We also observed that, at
      least at some loci, the parental genetics might be important in predicting the
      risk of cancer in this pediatric model of a complex disease. Taken together,
      these results indicate that the investigation of a single enzyme and/or a single
      genotype might not be sufficient to explain the etiology of childhood leukemia
      because of the complexity of the environment and that of the inter-individual
      variability in cancer susceptibility.

PMID- 16980229
TI  - [Clinical practice guideline on peritoneal carcinomatosis treatment using
      surgical cytoreduction and hyperthermic intraoperative intraperitoneal
      chemotherapy].
AB  - In 2005, the Comite de l'evolution des pratiques en oncologie (CEPO) took it upon
      itself to develop a clinical practice guideline to determine the clinical value
      of surgical cytoreduction followed by hyperthermic intraoperative intraperitoneal
      chemotherapy (HIPEC) for treating peritoneal carcinomatosis stemming from
      colorectal cancer, cancers of the appendix and stomach, pseudomyxoma peritonei,
      and mesothelioma of the peritoneum. A review of the scientific literature was
      performed using the PubMed search engine. The period covered extended from
      January 1990 to January 2006, inclusively. The scientific literature search was
      limited to clinical trials (minimum phase II) and organizations elaborating
      clinical practice recommendations. Twenty-six studies were identified. Of these,
      only one was phase III. Although some of these studies have demonstrated a
      benefit from this treatment in terms of patient survival, HIPEC remains a complex
      procedure whose optimal use is uncertain. Given the morbidity and mortality
      associated with this treatment, this procedure requires a high level of
      expertise. Considering the evidence available, the CEPO recommends: 1) that
      complete cytoreduction followed by HIPEC be used in a clinical research context
      only, preferably in the presence of an isolated peritoneal carcinomatosis
      stemming from colorectal cancer, cancer of the appendix, peritoneal pseudomyxoma,
      or mesothelioma of the peritoneum; 2) that studies be conducted only in
      specialized centers with the necessary expertise and technical resources.

PMID- 16980230
TI  - [PAX gene function during kidney tumorigenesis: a comparative approach].
AB  - The rising incidence of cancers affecting the kidney emphasizes the need to
      identify the molecular pathways involved in the initiation and progression of
      kidney tumors in order to counter this phenomenon. For many years, genes
      belonging to the PAX family have been the focus of intensive studies in the
      fields of organogenesis and tumorigenesis. PAX2 and PAX8 encode transcription
      factors essential for embryonic kidney development. Transcriptionnal repression
      of these factors is, however, required to allow terminal differentiation of renal
      epithelia. In human, maintenance and reactivation of PAX2/8 expression are
      frequently observed in cases of Wilm's tumor and renal cell carcinoma. The
      precise role of PAX2/8 in kidney cancer is still elusive but results from several
      studies suggest the exertion of common functions during organogenesis and
      tumorigenesis of the kidney. Moreover, many members of the PAX family are
      involved in similar cellular processes such as differentiation/proliferation,
      motility and apoptosis. Thus, by comparing the functions exerted by PAX factors
      in several types of cancers should be useful to better define the specific
      contribution of PAX2/8 to kidney tumorigenesis.

PMID- 16980231
TI  - [Decoding the mode of action of the estrogen receptor through functional
      genomics].
AB  - Estradiol is a potent growth factor of breast cancer cells and inhibition of its
      activity has been a basis for the treatment of this disease for a long time.
      Estradiol exerts its action mainly through a nuclear receptor (ERalpha) that
      recognizes specific sites in the genome and regulates the transcription of
      neighboring genes. The identification of the repertoire of estrogen responsive
      genes is considered an essential step for our comprehension of the biological
      functions of the hormone and of the molecular mechanisms by which ERalpha control
      gene expression. The technology combining immunoprecipitation of DNA fragments
      and hybridization to DNA chips currently allows the rapid identification of
      transcription factor binding sites on a whole-genome level. The recent
      utilization of this technology has not only led to the identification of numerous
      ERalpha target genes in breast cancer cells, but has also revealed that the
      receptor requires the presence of another transcription factor, known as FOXA1,
      to activate a specific subset of these genes. These studies have thus shown that
      factors like FOXA1 can be utilized to compartmentalize the action of the hormone,
      suggesting new opportunities to target more precisely the action of nuclear
      receptors for the prevention and treatment of hormone-dependent cancer.

PMID- 16980232
TI  - [NFkappaB : a new marker kappable of predicting prostate cancer outcome].
AB  - Prostate cancer is the most commonly diagnosed malignancy and the third cause of
      cancer-related death in Canadian men. Although most tumors are detected at an
      early stage and treated efficiently, a number of these cases will progress to a
      metastatic and hormone-refractory state where therapeutic options are essentially
      palliative. Due to a limited number of clinical prognostic markers, it is often
      difficult to identify cancers at risk of progression. To address this problem,
      uro-oncologic researchers are turning to molecular markers that can be detected
      biochemically in the blood or urine, as well as by immunohistochemistry on
      prostate cancer tissues. These markers are generally involved in cellular
      processes such as cell proliferation, apoptosis, and angiogenesis. Among the most
      promising markers is the transcription factor NFkappaB that controls the
      expression of many genes that play a role in oncogenesis. In particular,
      immunohistochemical analyses have shown that the nuclear expression of the RelA
      subunit in primary prostate tumors is associated with poor clinical outcome.
      Indeed, the nuclear localization of RelA upgrades the histological grade to allow
      a better classification of patients at risk of progression. Moreover, nuclear
      RelA is an independent predictor of biochemical recurrence and lymph node
      metastasis. Other subunits of the NFkappaB family may also become useful
      prognostic markers since they are also detected in the nucleus of prostate cancer
      cells. The addition of NFkappaB and other molecular markers to current clinical
      markers will facilitate the identification of high risk patients and guide
      clinicians in the choice of an appropriate therapeutic approach.

PMID- 16980233
TI  - [The use of mesenchymal stromal cells in oncology and cell therapy].
AB  - The unique properties of stem cells are opening the door for the development of
      new therapeutic approaches notably in oncology and regenerative medicine.
      Embryonic stem cells are theoretically very promising for that purpose. However,
      autologous stem cells derived from blood and bone marrow are the ones which have
      been tested in clinical trials. Amongst these, adult mesenchymal stromal cells
      (MSCs) possess particularly attracting properties, as they are easily expanded in
      vitro and possess the potential to differentiate into multiple cell lineages.
      Moreover, MSCs can be genetically modified and utilized as a biopharmaceutical.
      Several research groups are currently investigating both the fundamental
      properties of MSCs and applicable therapies derived from their use, particularly
      in cardiology but also in cancer and immunomodulation. Recently, we described
      that under appropriate stimulation, MSCs can behave as potent antigen-presenting
      cells (APCs) which is of interest in our understanding of hematopoietic system
      immunobiology. In addition, the antigen-presenting functions of MSC could
      theoretically be exploited as a new therapeutic tool in cancer therapy in order
      to amplify immune responses against tumor-specific antigens. In addition,
      genetically-modified MSCs are widely tested in preclinical studies and we will
      here present our results regarding IL2-producing MSCs as an anticancer agent. In
      Canada, the activities within the field of progenitor and stem cell therapeutics
      has been consolidated within the National Canadian Stem Cell Network which groups
      researchers, clinicians, engineers and ethicists, all dedicated to study this new
      promising pharmaceutical avenue.

PMID- 16980234
TI  - [Pre-mRNA alternative splicing in cancer: functional impact, molecular mechanisms
      and therapeutic perspectives].
AB  - For most of the 25,000 human genes, the removal of introns by pre-messenger RNA
      splicing represents an essential step towards the production of functional
      messenger RNAs. Moreover, a majority of pre-messenger RNAs is alternatively
      spliced to yield different messenger RNAs. Cancer cells often display aberrant
      profiles of alternative splicing producing isoforms that can stimulate cell
      proliferation and migration or improve resistance to apoptosis. While mutations
      at splice sites or in splicing control elements have been identified, changes are
      also caused by alterations in the expression of proteins that affect splice site
      selection. Current challenges consist in documenting the functional diversity
      generated by alternative splicing and its contribution to different types of
      cancers. The development of innovative approaches aimed at reprogramming
      alternative splicing offers promising perspectives in cancer therapy.

PMID- 16980235
TI  - [Alternative cell death pathways: lessons learned from a viral protein].
AB  - Evidence indicates that a limited set of common genetic alterations is
      responsible for tumor progression and cancer cell resistance to current
      therapies. The ability of tumor cells to escape apoptosis induction, which
      normally occurs in response to deregulated oncogenic signaling, is a critical
      one. Recent work supports the existence of alternative physiological death
      programs, which seem effective in cancer cells bearing multiple defects in
      apoptotic regulators. The goal of this review is to highlight the importance of
      these alternative death programs and to present the adenovirus E4orf4 protein
      (Early region 4 open reading frame 4), as a unique molecular tool to identify key
      regulators of these pathways in cancer cells. Evidence indicates that E4orf4
      hijacks the oncogenic functions of Src tyrosine kinases to activate a cell death
      program in cancer cells, which does not rely on the classical caspase pathways
      and bypasses Bcl-2. Recent findings support a critical role for endosomes
      associated actin dynamics downstream of E4orf4-Src signaling, in the regulation
      of this cell death pathway.

PMID- 16980236
TI  - Breast cancer-derived factors facilitate osteolytic bone metastasis.
AB  - Bone is the most common site of breast cancer metastasis. Skeletal metastases
      resulting from breast cancer are most often osteolytic, and contribute to the
      morbidity and mortality associated with this disease. Over the past several
      years, significant effort has been focused on elucidating the molecular
      mechanisms that govern this process. To accomplish this task, animal model
      systems have been generated to study the process of breast cancer metastasis to
      bone. These include: intraosseous injection that models tumor growth in the bone
      marrow, cardiac injections that permit cancer cell dissemination to the bone
      marrow from the bloodstream, and spontaneous bone metastasis originating from the
      mammary gland. Importantly, these various model systems have been combined with
      gene expression profiling to compare breast cancer populations with distinct bone
      metastatic potentials in the hopes of finding the genes that facilitate this
      process. The result has been the accumulation of an impressive body of evidence
      detailing a complex web of interactions between breast cancer cells, the
      mineralized bone matrix and host cells resident in bone; such as osteoblasts,
      osteoclasts and bone marrow endothelium. In this review we will address new
      developments that underscore the importance of secreted proteins and cell surface
      receptors expressed on breast cancer cells that play key roles in promoting bone
      resorption and tumor growth. Recent results from both basic and clinical research
      reveal that similar metastatic functions, such as adhesion and invasion, are
      conserved across a variety of bone metastatic breast cancer cells and different
      sets of genes can fulfill these requirements.

PMID- 16980237
TI  - [Proteases by reactive stromal cells in cancer: an attractive therapeutic
      target].
AB  - Cancer-associated or reactive stromal cells are composed of endothelial and
      inflammatory cells as well as of spindle cells such as fibroblasts and
      myofibroblasts. In addition to participating to the tumor tissue frame, these
      cells contribute actively to tumor nutrition and progression through neo
      angiogenesis and production of a variety of molecules including numerous
      proteases, of which a number (MMP14, MMP11, FAP and uPA) are almost exclusively
      produced by reactive stromal cells. Cancer cells interact with reactive stromal
      cells which involves a large number of proteases. Several molecules (TGFbeta,
      PDGF, EMMPRIN) produced by cancer cells induce the production of stromal
      proteases which in turn stimulate cancer cells through binding to a receptor (for
      example, MMP-2 and integrin alpha v beta 3). Our experience shows that protease
      overexpression by reactive stromal cells (cathepsin D, MMP-11, MMP-14) leads to
      an adverse clinical course in breast cancer. Phenotypic and genotypic differences
      were found between reactive stromal cells and fibroblasts of normal tissue and
      our research team found that reactive stromal cells also respond differently to
      similar stimulations in different individuals. These results support the
      hypothesis that the biologic behaviour of cancer is not only dependent on tumour
      characteristics but also on those of patients'stromal cells and that comparable
      tumours in two individuals may follow different clinical courses. These studies
      and our experience underscores the importance of characterising cancer-associated
      reactive stromal cells because of the therapeutic potential of this approach.
      Furthermore, reactive stromal cells should be genetically more stable that cancer
      cells and, in theory, should less likely develop mutations and treatment
      resistance.

PMID- 16980238
TI  - [Keyrole of endocrinology in the victory against prostate cancer].
AB  - The most significant discovery of the last quarter of the XXth century in the
      field of prostate cancer is probably the observation that the human prostate
      synthesizes locally an amount of androgens from the inactive steroid precursors
      dehydroepiandrosterone (DHEA) and its sulfate DHEA-S that is approximately
      equivalent to the androgens made in the testis. Based upon this observation, two
      important discoveries also made by our group are applied worlwide, namely the use
      of GnRH (gonadotropin -releasing hormone) agonists that completely block
      testicular androgen secretion, while, simultaneously, the androgens made locally
      in the prostate from DHEA are blocked in their access to the androgen receptor by
      a pure antiandrogen (flutamide, bicalutamide or nilutamide). This treatment,
      called combined androgen blockade, has been the first treatment demonstrated to
      prolong life in prostate cancer in prospective and randomized studies. While the
      first studies were performed in patients with advanced and metastatic disease,
      our recent data indicate a much higher efficacy of the same treatment applied to
      localized prostate cancer, thus leading to an at least 90 % possibility of cure.
      In fact, the lifesaving benefits of androgen blockade in prostate cancer have
      been largely underestimated. When compared to other cancer therapies, the results
      obtained are quite remarkable. A recent metaanalysis of all clinical trial data
      mostly gives the credit to follow-up hormone therapy. "Hormonal treatment as a
      whole works ridiculously well", as reported by Arnst. In fact, while death rates
      decreased by 1.1 % per year from 1993 to 2001 for all cancers combined, prostate
      cancer showed a larger decrease at 3.6 %. Although improvements in surgery and
      radiotherapy are likely to play a role, a study by Frank R. Lichtenberg using
      National Cancer Institute data obtained from 2.1 million cancer patients, has
      concluded that "cancer-fighting drugs improved survival rates, especially for
      cancer of the prostate, where drug innovations have been the greatest". The
      knowledge about the absence of development of resistance to androgen blockade in
      localized prostate cancer is extremely important. In fact, it is often
      erroneously believed that androgen blockade should not be administered early
      because resistance to treatment will develop and one might as well wait to use
      androgen blockade at a later stage of the disease. In fact, deferring treatment
      implies that, very often, it will then be too late, because after the cancer has
      migrated to the bones, resistance to treatment can no more be avoided. It should
      be realized that when prostate cancer is first detected, even by screening, the
      cancer is not small since its diameter is of the order of 1 cm or more. This is
      the most appropriate time to treat with the strong hope of a cure. With the
      presently available techniques, screening can diagnose prostate cancer at a
      clinically localized stage in 99 % of cases. Such an early diagnosis permits
      immediate treatment with a curative intent, combined androgen blockade (CAB)
      being a truly efficient alternative especially in older patients. Most
      importantly, CAB must be used immediately in patients who fail radical
      prostatectomy, radiotherapy of brachytherapy. When androgen blockade is used, it
      should always be combined androgen blockade. Using this strategy, based upon
      today's available diagnostic and therapeutic approaches, death from prostate
      cancer can be an exception, confirming that victory against prostate cancer is
      achieved.

PMID- 16980239
TI  - [Intraperitoneal chemotherapy for ovarian cancer: a complex strategy but what an
      exciting avenue!].

PMID- 16980240
TI  - Targeting DNA methylation in cancer.
AB  - Cancer growth and metastasis require the coordinate change in gene expression of
      different sets of genes. While genetic alterations can account for some of these
      changes, many of the changes in gene expression observed in cancer are caused by
      epigenetic modifications. The epigenome consists of the chromatin and its
      modifications, the "histone code" as well as the pattern of distribution of
      covalent modifications of cytosines residing in the dinucleotide sequence CG by
      methylation. The normal pattern of distribution of DNA methylation is altered in
      cancer. A number of genes are regionally hypermethylated but many parts of the
      genome are hypomethylated. Hypermethylation of tumor suppressor genes is involved
      in silencing of strategic genes. DNA hypermethylation has received much attention
      and a number of clinical trials are underway with different inhibitors of DNA
      methylating enzymes. It is now becoming clear however that hypomethylation also
      plays a role in cancer by activating genes required for invasion and metastasis.
      The potential therapeutic implications of targeting DNA methylation in cancer are
      discussed.

PMID- 16980241
TI  - Pretreatment of human epidermal keratinocytes with D,L-sulforaphane protects
      against sulfur mustard cytotoxicity.
AB  - Sulfur mustard (SM) is a powerful cytotoxic agent as well as a potent vesicant,
      mutagen, and carcinogen. This compound reacts with glutathione (GSH) and forms
      GSH-SM conjugates that appear to be excreted through the mercapturic acid pathway
      in mammals. The question of whether glutathione-S-transferases (GST) are involved
      in enzymatic formation of these conjugates remains unresolved. In previous
      studies, ethacrynic acid (EAA), a putative inhibitor of this transferase, and
      oltipraz, a known inducer,were ineffective in modulating this enzyme in cultured
      normal human epidermal keratinocytes (NHEK) so this hypothesis could not be
      tested. Higher levels of intracellular GSH appeared to be solely responsible for
      resistance of EAA-pretreated cells to SM. A better inducer of GST was needed to
      test whether this enzyme could be used to modify cytotoxicity following SM
      exposure. D,L-sulforaphane (DLS), a compound from broccoli extract known to be a
      potent inducer of this enzyme, was tested for GST induction in cultured NHEK. The
      enzyme levels increased optimally (40%) in these cells within 4 hours using 0.5
      microg DLS/mL over a 48 hour incubation period. When the drug was removed by
      washing, and pretreated cells were challenged with 0-200 microM SM, there was a
      10%-15% increase in survival at 24 hours compared with non-pretreated SM
      controls. This protective effect due to increased levels of GST was abolished at
      300 microM sulfur mustard, where there was no difference in survival between
      pretreated and non-pretreated controls. Glutathione levels were also assessed and
      showed no increase at 4 hours in cultured NHEK with DLS pretreatment and appear
      not to be responsible for this protection against SM.

PMID- 16980242
TI  - A double-blind, vehicle-controlled clinical study to evaluate the efficacy of
      MAS065D (XClair), a hyaluronic acid-based formulation, in the management of
      radiation-induced dermatitis.
AB  - This study was designed to assess the efficacy and tolerability of MAS065D
      (Xclair) compared to a vehicle control in the management of radiation dermatitis
      in patients receiving radiotherapy for breast cancer. Twenty patients were
      randomized blindly to use the two study substances, three times daily, on
      separate sections of irradiated skin throughout the duration of radiotherapy and
      for two weeks afterwards. Patients were monitored before therapy, weekly during
      therapy, and for 2 weeks after radiotherapy was completed. Skin appearance
      according to National Cancer Institute (NCI) toxicity criteria, erythema rating,
      transepidermal water loss (TEWL), skin hydration, patients' view of itch, pain,
      acceptance, and view of each cream and adverse events, were monitored; at the
      final visit patients and investigators expressed their preference for one of the
      creams. MAS065D showed statistically significant superiority in the outcomes of
      NCI grading for radiation dermatitis and erythema. Patients' and investigators'
      preferences for one of the study substances were statistically in favor of
      MAS065D. Very few patients recorded nonzero itch and pain scales, so no
      significant differences emerged between the two groups. It was concluded that
      MAS065D can provide an effective option for managing radiation dermatitis
      although further studies are needed to assess its effect on pain and itch.

PMID- 16980243
TI  - Visual system manifestations due to systemic exposure to mercury.
AB  - This article is a summary of the available literature on ocular symptoms due to
      systemic exposure to mercury. Mercury compounds are first described in terms of
      their different forms, industrial applications, mechanisms and routes of
      exposure, toxicity levels, and treatment methods. Eye symptoms are then
      characterized for organic and inorganic forms of mercury by using the form of
      various documented case studies of chronic and acute exposure to various mercury
      compounds.

PMID- 16980244
TI  - Hydrocarbon-based weapons maintenance compounds produce evidence of contact
      hypersensitivity in BALB/c mice.
AB  - Unprotected dermal contact with weapons maintenance materials is highly probable
      during cleaning and maintenance of firearms. Several weapons maintenance
      materials of interest to the Department of Defense were evaluated for their
      irritating and sensitizing potential in a modified local lymph node assay (LLNA).
      Female BALB/c mice (n = 5) were topically exposed to Break-Free CLP, Royco 634,
      TW-25B, MC-25, or MC-2500. All compounds tested produced a positive response for
      irritancy and lymphocyte proliferation. Break-Free CLP and Royco 634 produced the
      greatest dermal irritation and highest LLNA stimulation index. Phenotyping of
      draining lymph node cells from animals treated with Break-Free CLP suggest that
      this material induces T-cell-mediated contact sensitization (Type IV
      hypersensitivity) in mice. These findings support the recommendation that persons
      handling or using weapons maintenance materials should protect their skin from
      repeated contact by wearing appropriate personal protective equipment.

PMID- 16980245
TI  - Gender: a possible determinant in dosing of dermatologic drugs--an overview.
AB  - The role of gender in pharmacokinetics could play a significant role in tailoring
      HIV and other drug regimens. Here we investigate sex as a factor in saquinavir
      pharmacokinetics. The HIV-positive women who use saquinavir in combination with
      other protease inhibitors frequently demonstrate higher saquinavir concentrations
      than their male counterparts. The majority of the data indicates that the root of
      women's higher saquinavir concentrations is not inherent to their gender. Rather,
      extenuating factors associated with HIV play a prominent role in the observed
      difference between men and women's pharmacokinetic parameters. The source of
      observed differences in saquinavir pharmacokinetics could not be definitively
      traced to CYP3A, the enzyme responsible for saquinavir's metabolism or drug
      transporters. Hormonal changes associated with HIV infection together with
      concurrent use of other protease inhibitors could help explain development of sex
      differences. These findings can be used to further investigate when and why
      gender-based differences in saquinavir pharmacokinetics exist and possible future
      dosage and therapy considerations. Our knowledge of gender-related
      pharmacokinetics should be extended for other systemic drugs in dermatology.

PMID- 16980246
TI  - Percutaneous absorption of crotamiton in man following single and multiple
      dosing.
AB  - PURPOSE: Crotamiton is a topical drug used in the treatment of scabies and
      pruritus. We determined its percutaneous absorption following single and multiple
      dosing in normal skin. METHODS: We used in vivo measurement of percutaneous
      absorption of [14C] crotamiton in a multidose regimen by measuring urinary
      excretion and liquid scintillation counting in three groups of four healthy
      volunteers. The Feldmann urinary excretion method was utilized to ascertain
      percutaneous absorption. Our results showed that tape stripping does not increase
      percutaneous absorption of crotamiton; upon repeated application.

PMID- 16980247
TI  - Prediction of eye irritation potential of surfactant-based rinse-off personal
      care formulations by the bovine corneal opacity and permeability (BCOP) assay.
AB  - Evaluation of eye irritation potential is a routine part of product safety
      testing. Many companies have elected to use in vitro methods for this evaluation.
      We used the bovine corneal opacity and permeability (BCOP) assay for the
      prediction of the eye irritation potential of surfactant-based rinse-off personal
      care formulations in this study because of its positive performance in previous
      studies (1), and its potential to measure depth of injury through histological
      evaluation. The BCOP uses isolated corneas maintained in short-term organ culture
      and measures changes in opacity and epithelial barrier integrity (as determined
      by fluorescein passage through the cornea). Surfactants (anionic and nonionic)
      used in personal care formulations induce only small increases in direct opacity
      but the degree of epithelial damage is reflected in permeability measurement
      (OD490). The permeability measurement is the primary endpoint for this class of
      products. Marketed liquid hand soap was selected as the benchmark due to
      extensive in vivo and market history data. Using the liquid hand soap, a 25% v/v
      aqueous dilution with a 30-minute exposure produced the optimal resolution. A
      series of products with known in vivo eye irritation scores were evaluated to
      establish a prediction model. Histological evaluation was used to compare the
      degree of tissue damage to the permeability scores. Based on the permeability
      scores and histological review, the testing protocol for a surfactant-based rinse
      off personal care formulation was developed using a 25% v/v aqueous dilution, a
      30-minute exposure, concurrent testing of the benchmark control, and use of
      permeability measurements as the endpoint for the evaluation of eye irritation
      potential.

PMID- 16980249
TI  - Left hemisphere dominance for movement.
AB  - Clinical neuropsychology's dependence upon a core scientific background in
      clinical neuropsychology, and clinical psychology, neurology, and neuroanatomy,
      as well as biopsychology, cognitive neuroscience, and cognitive science is the
      basis of its designation as an APA-approved clinical specialty. This dependence
      highlights the importance of these scientific underpinnings and the scientist
      practitioner model of training, detailed in the Houston Guidelines. This
      presentation is meant to demonstrate that cognitive neuroscience research should
      influence our conception of brain behavior relationships, which, in turn, should
      influence our clinical work. In addition, I want to illustrate how the
      utilization of converging methods, which is an increasingly popular approach to
      research, can ensure more valid conclusions about the neuroanatomical substrates
      for complex skills. Limb apraxia will be used as an example of a deficit that has
      functional implications and whose cognitive mechanisms and neuroanatomical
      correlates are better understood as a result of research that combines
      neuroanatomical imaging of brain damaged patients, functional imaging, and
      cognitive paradigms. This work demonstrates that left frontoparietal circuits
      control limb praxis and motor sequencing, suggesting that these complex motor
      skills should be examined in patients with such damage.

PMID- 16980250
TI  - Neuropsychological differentiation of dementia with Lewy bodies from normal aging
      and Alzheimer's disease.
AB  - We examined the diagnostic utility of selected neuropsychological measures in the
      differentiation of dementia with Lewy bodies (DLB) from normal aging and
      Alzheimer's disease (AD). Patients with DLB (n = 87), AD (n = 138), and a group
      of normal controls (n = 103) were recruited from the Mayo Alzheimer's disease
      patient registry and Alzheimer's Disease Research Center. Neuropsychological
      measures shown to have utility in previous studies were included in the analysis.
      The final multivariate logistic regression model distinguishing DLB from normal
      controls included Auditory Verbal Learning Test (AVLT) percent retention, Block
      Design, Trail Making Test-Part A, and Benton Visual Form Discrimination. This
      model has a sensitivity of 88.6% and specificity of 96.1%. The final multivariate
      logistic model distinguishing DLB from AD included Trail Making Part A, Boston
      Naming Test (BNT), AVLT percent retention, and copy of the Rey-Osterrieth Complex
      Figure. This model had a sensitivity of 83.3% and a specificity of 91.4%. AVLT
      and BNT had negative coefficients, indicating that lower scores decreased the
      likelihood of DLB relative to AD. These finding extend prior research suggesting
      a cognitive profile that can aid in the clinical diagnosis of DLB. Early
      attention and visual perceptual disturbance suggests DLB, while early impairment
      in memory and naming suggests AD.

PMID- 16980251
TI  - IQ-based norms for highly intelligent adults.
AB  - This study presents normative data of commonly used neuropsychological tests
      administered to 75 individuals with high levels of intelligence (estimated IQ >
      or = 120). Participants were living independently in the community with ages
      ranging from 44 to 86. To avoid including individuals with an incipient dementia,
      we selected subjects who scored within the normal range on all cognitive tests
      for at least a two-year period. The norms are presented in table format to help
      clinicians easily identify a typical cognitive performance in highly intelligent
      individuals and to provide a useful guide for detecting abnormal cognitive
      decline in individuals at risk for progressive dementia.

PMID- 16980252
TI  - Fine tuning recommendations for older adults with memory complaints: using the
      Independent Living Scales with the Dementia Rating Scale.
AB  - The purpose of this study was to describe how functional test performance changed
      as global cognitive functioning dropped, as well as to examine the relationship
      of demographic variables and depression with functional test results. We found
      that level of performance on the Independent Living Scales (ILS) correlated
      highly with Dementia Rating Scale (DRS) scores in 83 older adults presenting for
      clinical neuropsychological assessment, while correlations with demographic
      factors and depression were nonsignificant or modest. Based on DRS scores, we
      divided our sample into four groups: normal cognitive status, borderline
      cognitive impairment, likely mild dementia, and likely moderate dementia. ILS
      profiles of the borderline impairment and mild dementia groups were similar and
      reflected particularly poor performance on subscales tapping financial management
      and everyday memory. Individuals with likely moderate dementia were markedly
      impaired on all subscales.

PMID- 16980253
TI  - An empirical basis for domains in the analysis of dependency in the activities of
      daily living (ADL): results of a confirmatory factor analysis of the Cleveland
      Scale for Activities of Daily Living (CSADL).
AB  - This study examines the empirical basis for dividing activities of daily living
      (ADLs) into broad behavioral domains. Following an exploratory factor analysis of
      results from the Cleveland Scale for Activities of Daily Living (CSADL), a two
      factor model of ADLs was tested in a confirmatory factor analysis using two
      groups of demented patients. The model, which included a Basic and an
      Instrumental factor, was confirmed. Comparison of the item composition of the
      CSADL factors with a priori domains used by other ADL scales suggested that the
      results of the present study are broadly generalizable. The two factors are
      correlated, and cautions were raised concerning the likelihood that many ADL
      items may reflect both basic and instrumental domains.

PMID- 16980254
TI  - New scores for the Category Test: measures of interference for subtests 5 and 6.
AB  - The Category Test is a well-known neuropsychological instrument used to assess
      concept formation and higher executive abilities. The present study investigated
      the utility of additional scores for the Category Test. We used principles
      developed in cognitive psychology to create several new measures for subtests 5
      and 6 of this test. These scores were primarily designed to be sensitive to
      interference effects of learning decision rules from subtest 2, subtest 3, and
      subtest 4. The new scores as well as the total error scores from subtests 5 and 6
      were used to discriminate subjects with documented brain injury from subjects who
      were neurologically normal based on neuroimaging and neurologic evaluation. The
      Category Test was given following Reitan's (1979) instructions, with the
      exception that no additional prompting was given to participants who struggled
      early with the test in order to reduce the "executive" guidance of the examiner.
      Because any "interference" from earlier subtests on performance of subtest 5 and
      subtest 6 should be related to mastery of these earlier subtests, the normal
      group was matched to the brain-impaired group on which subtest(s) they learned.
      This resulted in four learning groups: (a) learned subtests 3 and 4; (b) learned
      subtest 4 but not 3; (c) learned subtest 3 but not 4; and (d) failed to learn
      either subtest. ANOVA analyses revealed that the three measures of interference
      were significantly greater in the brain-damaged group than in the normal
      controls. Also, specific interference measures were related to specific prior
      subtest mastery, thus providing support for a proactive interference effect. In
      addition, we have evidence that our new measures may be selectively sensitive to
      frontal system dysfunction.

PMID- 16980255
TI  - Sensitivity of computerized neuropsychological screening in depressed university
      students.
AB  - This study examined the sensitivity of a computerized neuropsychological
      screening (ImPACT) to the cognitive effects of depression in a sample of 20
      students with suspected depression and 20 healthy university students matched for
      gender, age, and education. Students with depression had slower reaction times (p
      < .02; d = .82, large effect) and processing speeds (p < .03; d = .77, large
      effect). The brevity and sensitivity of ImPACT to the cognitive effects of
      depression warrants further research with psychiatric populations.

PMID- 16980256
TI  - The validity of the repeatable battery of neuropsychological status in acute
      stroke.
AB  - The construct validity of the Repeatable Battery for the Assessment of
      Neuropsychological Status (RBANS) was investigated in a sample of 210 acute
      ischemic stroke patients seen on an inpatient rehabilitation unit.
      Intercorrelations between the six index scores were found to be relatively
      consistent with previously published work. A principal components analysis
      yielded a two-factor (Language/Verbal Memory and Visuospatial/Visual Memory)
      solution that accounted for 61% of the variance. Correlations generated between
      the resulting factor scores, the Controlled Oral Word Association Test (COWA),
      the Visual Form Discrimination Test (VFD), Boston Diagnostic Aphasia Examination
      (BDAE) Complex Ideational Material Test (CIM), the presence of neglect as
      determined by Line Bisection Test performance, and the Mini Mental Status
      Examination (MMSE) supported the validity of these factors. A comparison of the
      obtained factor scores in a subgroup of 111 left and right hemispheric stroke
      patients showed that the left hemispheric stroke patients performed more poorly
      on the Language/Verbal Memory factor score than did right hemispheric stroke
      patients while the converse was true for the Visuospatial/Visual Memory factor
      score. Implications for the construct validity of the RBANS and its use and
      interpretation in clinical assessment are discussed.

PMID- 16980257
TI  - Norwegian norms and factor-structure of phonemic and semantic word list
      generation.
AB  - Word list generation (WLG) tasks are used world wide as measures of executive
      function, although the tests are sensitive also to deficits in other cognitive
      functions. Norms derived from English-speaking samples are often used in Norway,
      even though the consequences of language differences are not yet been assessed.
      The reliability of WLG testing in Norway is increased by the norms presented in
      the first part of the study. The validity of WLG tests as measures of executive
      function is addressed in the second part, by performing a factor-analysis of
      neuropsychological performance in a mixed psychiatric sample. Education
      contributed most to performance. There were no sex-differences in overall
      performance. Factor analysis indicated that phonemic WLG is a more specific
      measure of executive function than semantic WLG. Semantic WLG correlated higher
      with basal processing speed, thus being more sensitive to aging. In conclusion
      the clinical neuropsychologist is advised to control for reduction in basal
      processing speed before interpreting WLG scores as specific deficits in executive
      function. The Norwegian norms correspond well with most comparable studies in
      other languages, thus failing to show any language specific effects.

PMID- 16980258
TI  - Interrater and test-retest reliability of a fixed condition design fluency test.
AB  - Despite its potential as a unique neuropsychological test, the emergence of a
      psychometrically sound research foundation for Jones-Gotman and Milner's (1977)
      Design Fluency Test (DFT) has been constrained by the lack of consistent
      administration and scoring practices and limited information about its
      reliability. Here we describe an approach to administering and scoring the fixed
      condition DFT that is modeled on Jones-Gotman and Milner's original method and
      that clarifies procedural ambiguities. Results include interrater and long-term
      test-retest reliability analyses using this approach. First, based on five raters
      who scored 50 DFT protocols, good to excellent intra-class correlation
      coefficients were obtained for all DFT scores. Second, in a broadly
      representative sample of 87 healthy adults who were tested twice over an average
      of 5 1/2 years, the test-retest reliabilities for total and novel design scores
      ranged from good to excellent. This study demonstrates that the fixed condition
      DFT can be scored reliably using these procedures and that the reliability
      coefficients for DFT total and novel designs scores are comparable to those of
      other commonly used neuropsychological tests.

PMID- 16980259
TI  - Detecting feigned impairment with the digit span and vocabulary subtests of the
      Wechsler Adult Intelligence Scale-third edition.
AB  - The WAIS-III Digit Span and Vocabulary subtests were investigated as indicators
      of feigned cognitive impairment. Participants included 64 undergraduates randomly
      assigned to control, symptom-coached, or test-coached groups. Six previously
      researched validity indicators were examined. We hypothesized that symptom
      coached participants would perform worse relative to test-coached simulators.
      Analyses determined both simulator groups performed lower than controls on all
      indicators except Vocabulary. Symptom-coached participants, however, did not
      differ from test-coached participants on any indicator. Classification accuracies
      for these six indicators ranged from 42 to 78%. While the WAIS-III validity
      indicators hold some promise, they should not be employed as independent
      measures.

PMID- 16980260
TI  - Noncredible psychiatric and cognitive symptoms in a workers' compensation
      "stress" claim sample.
AB  - Information is lacking regarding the prevalence of fraudulent psychiatric and
      cognitive symptoms in the "stress" claim workers' compensation population. Using
      various validity indices (Negative Impression Scale, the Malingering Index, and
      the Rogers Discriminant Function) of the Personality Assessment Inventory (PAI),
      between 9 and 29% of 233 workers' compensation "stress" claim litigants were
      identified as exhibiting noncredible psychiatric symptoms. In addition, 15% of
      the subjects were determined to have noncredible cognitive symptoms on the Dot
      Counting Test, although only 8% displayed suspect effort on the 15-Item
      Memorization Test, with 5% of subjects failing both cognitive effort tests. The
      percentage of positive identifications on both a PAI and cognitive credibility
      index ranged from only 2 to 4%. Further, correlations between PAI validity
      indices and cognitive effort scales were nonexistent to modest, indicating that
      the psychiatric and cognitive credibility indices are measuring different aspects
      of noncredible symptom production. It was predicted that the PAI profiles of the
      participants displaying suspect cognitive symptoms would be elevated on the
      Somatic Concerns, Antisocial, and/or Borderline scales; however, elevations
      (relative to subjects with credible cognitive performance) were instead noted on
      the Somatic Concerns, Depression, Anxiety, Anxiety-Related Disorders, and
      Schizophrenia scales.

PMID- 16980261
TI  - Has the rolling uterus finally gathered moss? Somatization and malingering of
      cognitive deficit in six cases of "toxic mold" exposure.
AB  - This article reports six cases of litigants claiming neuropsychiatric impairment
      due to toxic mold exposure. In spite of recent growth in personal injury claims
      due to mold, numerous reviews of the literature have failed to find an
      association between environmental exposure to mold and neuropsychiatric and/or
      neuropsychological damage. We report data on six patients claiming harm, 4 of
      whom revealed a long history of somatization by history and psychological
      testing, and 2 of whom were shown to be malingering based on multiple indicators
      of non-credible performance. Of the 6 patients, only the 2 somatoform patients
      who were also depressed showed credible evidence of neuropsychological
      dysfunction. We review two other studies that have examined the link between mold
      exposure and cognitive impairment and discuss their limitations in view of the
      presenting behaviors of these 6 patients. Until the literature has established a
      credible link between mold and neuropsychiatric/neuropsychological impairment,
      jurists and clinicians must consider the ethics and potential harm of exposing
      somatoform patients to multiple unwarranted medical evaluations. Principles for
      forensic evaluations in this special population are reviewed.

PMID- 16980262
TI  - The Henry-Heilbronner Index: a 15-item empirically derived MMPI-2 subscale for
      identifying probable malingering in personal injury litigants and disability
      claimants.
AB  - A new 15-item MMPI-2 subscale, the Henry-Heilbronner Index (HHI), representing a
      "pseudosomatic factor," was empirically derived from both the 43-item Lees-Haley
      Fake Bad Scale (FBS) and the 17-item Shaw and Matthews' Pseudoneurologic Scale
      (PNS). The HHI was superior to both the FBS and PNS in identification of symptom
      exaggeration in personal injury litigants and disability claimants compared to
      non-litigating head-injured controls. Logistic regression analyses revealed that
      a cutscore of > or = 8 on the HHI was associated with good specificity (89%) and
      sensitivity (80%). These results suggest that the HHI may be useful in
      identifying personal injury litigants and disability claimants who exaggerate,
      overreport, or malinger physical symptoms on the MMPI-2 related to their current
      health and/or litigation status.

PMID- 16980263
TI  - Detecting insufficient effort using the Seashore Rhythm and Speech-Sounds
      Perception Tests in head injury.
AB  - This study examined the capacity of the Seashore Rhythm Test (SRT) and the Speech
      Sounds Perception Test (SSPT) to detect insufficient effort in a clinical sample.
      Forty-six participants with financially compensable mild head injury who obtained
      scores indicative of insufficient effort on multiple measures were compared to 49
      participants with brain injury who were not involved in litigation. Receiver
      operating characteristic (ROC) curve analysis indicated that both the SRT (AUC =
      .84) and SSPT (AUC = .80) were significant (p < .001) predictors of insufficient
      effort. Maximizing sensitivity and specificity, the optimal cutoff scores were 8
      errors on the SRT and 10 errors on the SSPT. Combining both variables into a
      logistic regression function increased the diagnostic efficiency.

PMID- 16980264
TI  - Classification accuracy of the Portland Digit Recognition Test in traumatic brain
      injury: results of a known-groups analysis.
AB  - The present study used a known-groups design to examine the accuracy of the
      Portland Digit Recognition Test (PDRT) in the detection of malingering in
      traumatic brain injury (TBI). Data were derived from 262 TBI patients who were
      classified as not malingering, possibly malingering, and malingering based on the
      Slick, Sherman, and Iverson (1999) criteria. The original PDRT cutoffs detected
      between 20 and 50% of malingering TBI patients with a false positive error rate
      of 5% or less. When the false positive error rate was held at 5%, across all item
      sets, sensitivity was as high as 70%. The results show that the original PDRT
      cutoffs are conservative and that higher scores detect more MND patients without
      causing the false positive error rate to become unacceptably high. Clinical
      application and future research needs are discussed.

PMID- 16980265
TI  - Compensation and malingering in traumatic brain injury: a dose-response
      relationship?
AB  - The purpose of this study was to determine if there is a dose-response
      relationship between potential monetary compensation and failure on psychological
      indicators of malingering in traumatic brain injury. 332 traumatic brain injury
      patients were divided into three groups based on incentive to perform poorly on
      neuropsychological testing: no incentive; limited incentive as provided by State
      law; high incentive as provided by Federal law. The rate of failure on five well
      validated malingering indicators across these groups was examined. Cases handled
      under Federal workers compensation laws showed considerably higher rates of
      failure and diagnosable malingering than cases handled under State law. The
      findings indicate that monetary compensation associated with workers compensation
      claims is a major motive for exaggeration and malingering of problems attributed
      to work-related brain injuries. The clinician's index of suspicion regarding
      exaggeration and malingering of symptoms and deficits should be much higher in
      the context of Federal workers compensation claims, particularly in patients who
      have suffered only mild traumatic brain injury.

PMID- 16980266
TI  - MMPI-2 profiles of persons with multiple chemical sensitivity.
AB  - We compared the MMPI-2 profiles of adults with multiple chemical sensitivity
      (MCS), epileptic seizures (ES), and nonepileptic seizures (NES). Both NES and MCS
      are medically unexplained conditions. In previous studies profiles associated
      with NES were elevated on scales Hs and Hy, compared with profiles associated
      with ES. We predicted that profiles associated with MCS would be elevated on Hs
      and Hy compared with the ES group. Patients with ES and NES were diagnosed after
      intensive EEG monitoring using published criteria. MCS was diagnosed if there was
      a complaint of illness in response to multiple common odors at levels that are
      not noxious to most people. All the MCS cases had legal claims for injury related
      to chemical exposures. The results showed that on MMPI-2 scales Hs, D, and Hy the
      MCS group had means significantly higher than both the ES and NES groups. Fake
      Bad Scale scores were elevated in 11 MCS cases, and regression-based estimates of
      Fake Bad Scale scores showed elevation in the MCS group compared with both
      seizure groups. We conclude that MMPI-2 data, obtained from people seeking
      financial compensation, indicate that there is a strong psychological component
      to MCS symptoms.

PMID- 16980267
TI  - Does effort suppress cognition after traumatic brain injury? A re-examination of
      the evidence for the Word Memory Test.
AB  - Green, Rohling, Lees-Haley, and Allen (2001) suggested that scores on a test of
      "effort," the Word Memory Test (WMT), explains more variance in outcome after
      brain injury than does injury severity. As a consequence, Green and colleagues
      recommend using the WMT to control for sub-optimal effort in neuropsychological
      evaluations and group research. We re-examine the evidence for their conclusions
      and argue that identifying a larger proportion of explained variance is not in
      itself evidence of validity unless the premise to be proven is already assumed,
      namely, that the test is a valid measure of effort. Instead, the crux of Green
      and colleagues claim for the validity of the WMT implies an interaction between
      effort and injury severity on outcome scores, although the specific interaction
      has not been tested in their previous research. We failed to find any evidence
      for this interaction in a sample of 100 Australian litigants. We conclude that
      our data do not support the view that effort, as measured by the WMT, interacts
      with injury severity to suppress cognition after brain injury.

PMID- 16980268
TI  - The utility of the Rey Word Recognition Test in the detection of suspect effort.
AB  - The Rey Word Recognition Test potentially represents an underutilized tool for
      clinicians to use in the detection of suspect effort. The present study examined
      the predictive accuracy of the test by examining the performance of three groups
      of participants: (a) 92 noncredible patients (as determined by failed
      psychometric and behavioral criteria and external motive to feign), (b) 51
      general clinical patients with no motive to feign, and (c) 31 learning disabled
      college students. Results demonstrated gender differences in performance that
      necessitated separate cutoff scores for men and women. Use of a cutoff score of <
      or = 7 words correctly recognized identified 80.5% of noncredible female patients
      while maintaining specificity of > 90%. However, to achieve this level of
      specificity in male noncredible patients, the cutoff score had to be lowered to <
      or = 5, with resultant sensitivity of only 62.7%. A combination variable
      (recognition correct minus false positive errors + number of words recognized
      from the first 8 words) showed enhanced sensitivity in identifying suspect effort
      in a subset of the noncredible sample who were claiming cognitive symptoms
      secondary to traumatic brain injury (i.e., cutoff score of < or = 9 = 81.6%
      sensitivity with 90% specificity). Results indicate that the Rey Word Recognition
      Test is an accurate and cost-effective method for the detection of noncredible
      cognitive performance.

PMID- 16980270
TI  - PLGA microspheres with high drug loading and high encapsulation efficiency
      prepared by a novel solvent evaporation technique.
AB  - PLGA microspheres with high drug loading and high encapsulation efficiency were
      fabricated by a novel solvent evaporation process-in-situ S/O/W process. Insulin
      was dissolved in DMSO and dispersed into DCM to form fine particles due to an
      anti-solvent effect. The in-situ formed suspension was then added into an aqueous
      phase and emulsified. Microspheres were formed following the evaporation of
      organic solvents. The experimental results showed that the modified S/O/W process
      could encapsulate more than 90%(w/w) insulin in the microspheres with a drug
      loading of over 15% and the initial burst was much less than microspheres made by
      a W1/O/W2 process. Compared with a traditional water-in-oil-in-water (W1/O/W2)
      process, the in-situ S/O/W process does not require high solubility of the
      encapsulated drug in water and, because no special pre-treatment is needed to
      reduce the particle size of the drug, it is superior to an ordinary S/O/W
      process. The in-situ S/O/W process is particularly applicable to encapsulate
      peptides and low molecular weight proteins.

PMID- 16980271
TI  - Celecoxib-loaded poly(D,L-lactide-co-glycolide) nanoparticles prepared using a
      novel and controllable combination of diffusion and emulsification steps as part
      of the salting-out procedure.
AB  - A novel procedure for the manufacture of celecoxib-loaded poly(D,L-lactide-co
      glycolide) (PLGA) nanoparticles is described that is based upon combining salting
      out and emulsion-evaporation steps. An entrapment efficiency, a measure of the
      actual to theoretical drug content, of 97.3% was achieved, being superior to that
      achieved when these popular techniques were used separately (emulsion
      evaporation, 40.1%; salting out, 10.0%). The ratio of a water miscible solvent
      (acetone) to a non water-miscible solvent (dichloromethane) was shown to be the
      primary determinants of size and drug loading. Once optimized, using an organic
      phase of 3 : 1 acetone : dichloromethane vol : vol ratio, further control on
      particle parameters could be exerted using modification of acetone diffusion by
      alterations in MgCl2 x 6H2O concentration. This step was shown to have a small
      effect on both the mean nanoparticle size and entrapment efficiency, but found to
      reduce the polydispersity considerably. Diffusion control using a 45% w/v MgCl2 x
      6H2O solution produced nanoparticles with a mean size of 151.4 nm, a
      polydispersity index of 0.023 and 98.1% entrapment efficiency. Electron
      microscopy showed the particles to be smooth and spherical. Sheer homogenization
      during the emulsification step was shown to be not as effective as sonication,
      with the latter technique able to produce nanoparticles after 1 min of
      application. Drug release studies across a semi-permeable membrane demonstrated a
      reduction in the burst effect as the ratio of acetone in the organic phase was
      increased. Calorimetry studies suggested that celecoxib existed in the
      nanoparticle as a molecular dispersion, with additional evidence for a strong
      interaction between the PLGA and the absorbed poly(vinyl alcohol) stabilizer.
      Formation of a strong interaction between celecoxib and PLGA, together with the
      formation of a radial drug gradient give a release profile that does not possess
      the prevalent burst effect seen with other nanoparticulate drug-loaded systems.

PMID- 16980272
TI  - Preparation of poly (alkylcyanoacrylate) nanoparticles by polymerization of water
      free microemulsions.
AB  - Phase diagrams of the pseudoternary systems ethyloleate, polyoxyethylene 20
      sorbitan mono-oleate/sorbitan monolaurate and propylene glycol with and without
      butanol as a co-surfactant were prepared. Areas containing optically isotropic,
      one-phase systems were identified and samples therein designated as droplet,
      bicontinuous or solution type microemulsions using conductivity, viscosity and
      self-diffusion NMR. Nanoparticles were prepared by polymerization of selected
      microemulsions with ethyl-2-cyanoacrylate and the morphology of the particles was
      investigated. Addition of monomer to all types of microemulsions led to the
      formation of nanoparticles, which had an average size of 244 +/- 25 nm, an
      average polydispersity index of 0.15 +/- 0.04 and a zeta-potential of -17 +/- 3
      mV. The formation of particles from water-free microemulsions of different types
      is surprising, particularly considering that polymerization is expected to occur
      at a water-oil interface by base-catalysed polymerization. It would appear that
      propylene glycol is sufficiently nucleophilic to initiate the polymerization. The
      use of water-free microemulsions as templates for the preparation of poly
      (alkylcyanoacrylate) nanoparticles opens up interesting opportunities for the
      encapsulation of bioactives which do not have suitable properties for
      encapsulation on the basis of water-containing microemulsions.

PMID- 16980273
TI  - Fucosphere--new microsphere carriers for peptide and protein delivery:
      preparation and in vitro characterization.
AB  - PURPOSE: Fucoidan is a complex polysaccharide containing sugars and high amounts
      of sulphate derived from marine brown algaes. In this study, a new microsphere
      delivery system based on cross-linking of fucoidan with chitosan, named
      Fucosphere, was evaluated as a drug carrier. Bovine serum albumin (BSA) was used
      as a model protein. The effect of fucoidan (1.5, 1.75, 2.0 and 2.5%), chitosan
      (0.25, 0.50 and 0.75%) and protein (0.25, 0.50 and 0.75%) concentrations, the
      origin of chitosan and the preparation methods of the particles on the
      microsphere characteristics were evaluated. METHODS: The microspheres were
      prepared by a simple method based on the cross-linking of the opposite charged
      biopolymers. The shape and surface morphologies of the particles were evaluated
      by scanning electron microscopy (SEM) and the size, charge and encapsulation
      capacity of the microspheres were determined. The released amount of BSA from the
      microspheres into phosphate buffered saline (PBS pH 7.4) was determined
      spectrophotometrically by the Bradford method. SDS-PAGE was performed to check
      the structural integrity of BSA after the preparation. RESULTS: Smooth and
      spherical microspheres between the size ranges of 0.61-1.28 microm were obtained.
      BSA was efficiently encapsulated into the microspheres (51.8-89.5%). All
      formulation parameters affected the encapsulation capacity of Fucosphere (p <
      0.05). The highest encapsulation was obtained with microspheres containing 2.5%
      of fucoidan (89.5%). CONCLUSIONS: The extent of drug release from the
      microspheres was dependent on the concentrations of polymers and BSA, chitosan
      origin and type of preparation method. When the addition methods of protein
      compared, BSA encapsulated into Fucosphere released slower than the adsorbed
      protein (E) (p < 0.05). The electrophoretic mobility values of Fucospheres
      changed between +6.9 and +32.3 mV. In general, BSA release from Fucosphere showed
      a three-phasic release curve. In conclusion, this new fucoidan microsphere system
      may be a potential delivery of macromolecular drug such as peptide and protein.

PMID- 16980274
TI  - Preparation, characterization, photocytotoxicity assay of PLGA nanoparticles
      containing zinc (II) phthalocyanine for photodynamic therapy use.
AB  - Nanoparticles containing Zinc (II) Phthalocyanine (ZnPc) were prepared by a
      spontaneous emulsification diffusion method utilizing poly-(D,L lactic-co
      glycolic acid) (PLGA), characterized and available in cellular culture. The
      process yield and encapsulation efficiency were 60% and 80%, respectively. The
      nanoparticles have a mean diameter of 200 nm, a narrow size distribution with
      polydispersive index of 0.15, smooth surface and spherical shape. ZnPc loaded
      nanoparticles maintain their photophysical behaviour after the encapsulation
      process. Photosensitizer released from nanoparticles was sustained with a burst
      effect of 10% for 3 days. The photocytotoxicity was evaluated on P388-D1 cells.
      They were incubated with ZnPc loaded Np by 6 h and exposed to light (675 nm) for
      120 s, and light dose of 30 J cm-2. After 24 h of incubation, the cellular
      viability was determined, obtaining 60% of cellular death. All the physical
      chemical and photobiological measurements performed allowed one conclude that
      ZnPc loaded PLGA nanoparticles are a promising drug delivery system for PDT.

PMID- 16980275
TI  - About mean diameter and size distributions of poly(lactide-co-glycolide) (PLG)
      microspheres.
AB  - Despite the importance of microsphere size for controlled drug delivery, little
      work has been done to quantitatively predict the distribution of microspheres
      from manufacturing techniques. This work presents a quantitative study that
      describes the size distribution of poly(lactide-co-glycolide) (PLG) microspheres.
      A fluid mechanics based correlation for the mean microsphere diameter is
      formulated based on the theory of emulsification in turbulent flow under non
      coalescing conditions. The correlation was constructed and validated with
      experimentally obtained mean microsphere diameters prepared at different stirring
      speeds. In addition, a Rosin Rammler distribution function was found to give an
      accurate representation of the microsphere distribution. The spread of the
      microsphere size distribution was found to decrease with stirring speed. With the
      validation of the mathematical correlation, it is now possible to have a good
      estimate of the average microsphere size prior to microsphere preparation. This
      is directly relevant to the pharmaceutical industry where microspheres of
      specified mean diameter and size distribution are desirable.

PMID- 16980277
TI  - Alkylcyanoacrylate nanocapsules prepared from mini-emulsions: a comparison with
      the conventional approach.
AB  - Polyalkylcyanoacrylate nanocapsules are being prepared using two different types
      of o/w-emulsions: a conventional emulsion generated by intensive stirring with a
      home-made device and a mini-emulsion produced by the action of ultrasonic
      dispersion, using the alkylcyanoacrylate monomer as a hydrophobic agent. The
      emulsions and the resulting nanocapsule dispersions are compared using various
      methods of physical characterization. The formation of solid capsules is
      indicated by solid state NMR spectra and atomic force microscopy. Differences
      between the results of both synthetic approaches are found in terms of particle
      size distribution, zeta potential and tendency towards particle agglomeration.
      Capsules prepared by ultrasound via the mini-emulsion pathway tend to be smaller
      and more monodisperse. Their zeta potential is negative with larger absolute
      values as compared to capsules obtained from conventional emulsions, leading to
      stronger repulsive interactions and a higher stability against capsule
      agglomeration.

PMID- 16980276
TI  - Implantation of vancomycin microspheres in blend with human/rabbit bone grafts to
      infected bone defects.
AB  - In orthopaedic applications, allografts are used for restoration of bone defects.
      In order to combine the effects of bone repair and to prevent the infection,
      antibiotic-impregnated bone grafts are under current investigation with promising
      early results. In this study, to preserve the stability of antibiotics and to
      provide appropriate release profiles for 4-6 weeks, antibiotic-loaded
      microspheres were administered in combination with allografts and vancomycin was
      the antibiotic loaded to microspheres. Particle size, surface characteristics,
      loading capacity and in vitro release characteristics of the microspheres with
      and without allografts were determined. In vivo studies were performed on rabbits
      and antibiotic amount was determined by a fluorescence polarization immunoassay
      (FPIA) method from synovial fluid sample aspirated. According to the results,
      although the in vitro study demonstrated effective antibiotic release of
      vancomycin from antibiotic-impregnated allografts for 5 weeks, in vivo conditions
      led to an early instability of the antibiotic (in powder form) and contrary to
      the high initial loading dose an effective release could not be obtained from the
      allografts after the first week. Following these studies, it was determined that
      antibiotic release over a minimum inhibitory concentration (MIC) for 6 weeks was
      realized from vancomycin-loaded microspheres which were implanted in a blend with
      allografts in bone defects. In conclusion, preservation of the antibiotic in
      microspheres maintained the bioactivity and provided the controlled antibiotic
      release, thus implantation of microspheres in a blend with allografts seemed to
      be a promising carrier system for the orthopaedic applications.

PMID- 16980278
TI  - Influence of surfactants, polymer and doxorubicin loading on the anti-tumour
      effect of poly(butyl cyanoacrylate) nanoparticles in a rat glioma model.
AB  - Poly(n-butyl cyanoacrylate) nanoparticles coated with polysorbate-80 can enable
      the transport of bound drugs across the blood-brain barrier (BBB) after i.v.
      injection. In the present study the influence of different formulation parameters
      on the anti-tumoural effects of doxorubicin nanoparticles against glioblastoma
      101/8 was investigated. The manufacturing parameters of poly(alkyl cyanoacrylate)
      doxorubicin-loaded nanoparticles were optimized concerning drug loading. The
      nanoparticles were coated with different surfactants and injected intravenously
      on days 2, 5 and 8 after intra-cranial implantation of glioblastoma 101/8 to
      rats. The survival times of all doxorubicin containing preparations, including a
      doxorubicin solution, increased the survival times significantly compared to
      untreated tumour-bearing rats. The most pronounced increase in survival was
      obtained with the poly(n-butyl cyanoacrylate) doxorubicin-loaded nanoparticles
      coated with polysorbate 80 and 35% of these animals survived for over 180 days
      (termination of the experiments). The other nanoparticle preparations yielded
      lower survival times. Poly(n-butyl cyanoacrylate) doxorubicin-loaded
      nanoparticles coated with polysorbate 80-coated proved to be very efficient
      against glioblastoma 101/8. The data suggest that the interaction of
      nanoparticles with the blood after injection as well as the enhanced permeability
      and retention effect (EPR effect) contributed differently to the anti-tumoural
      efficacy depending on nanoparticle formulation and surface properties.

PMID- 16980282
TI  - Flow studies in three-dimensional aorto-right coronary bypass graft system.
AB  - This paper presents the fluid dynamics of blood flow in a coronary bypass model
      of the aorto-right coronary bypass system. Three-dimensional computational fluid
      dynamic simulations are developed of the blood flow in coronary artery-bypass
      systems, using the computational fluid dynamics software (FLUENT 6.0.1). These
      blood flow simulations are performed within small intervals of the cardiac cycle,
      using input data consisting of physiological measurements of flow rates in the
      aorta, obtained from earlier studies. We have calculated the flow-field
      distributions of the velocity and the wall shear stress at four typical instants
      of the cardiac cycle, two during systole and two during the diastole phase. Plots
      of velocity vector and the wall shear stress are displayed in the aorto-graft
      coronary arterial flow-field domain, providing an insight into the link between
      fluid dynamics and arterial diseases. The prime regions of disturbed flow
      patterns are at the entrance into the graft from the aorta and at the exit from
      the graft into the right coronary artery. Our objective is to obtain an
      understanding of how the coronary artery is perfused by the graft, and thereby
      into the factors affecting graft patency.

PMID- 16980283
TI  - Effects of blood flow and vessel geometry on wall stress and rupture risk of
      abdominal aortic aneurysms.
AB  - Sudden rupture of abdominal aortic aneurysm (AAA), often without prior medical
      warning, is the 13th leading cause of mortality in the US. The local rupture is
      triggered when the elusive maximum local wall stress exceeds the patient's yield
      stress. Employing a validated fluid-structure interaction code, the coupled blood
      flow and AAA wall dynamics were simulated and analysed for two representative
      asymmetric AAAs with different neck angles and iliac bifurcations. It turned out
      that the AAA morphology plays an important role in wall deformation and stress
      distribution, and hence possible rupture. The neck angle substantially impacts
      flow fields. A large neck angle may cause strong irregular vortices in the AAA
      cavity and may influence the wall stress distribution remarkably. The rupture
      risk of lateral asymmetric AAAs is higher than for the anterior-posterior
      asymmetric types. The most likely rupture site is located near the anterior
      distal side for the anterior-posterior asymmetric AAA and the left distal side in
      the lateral asymmetric AAA.

PMID- 16980284
TI  - Analysis and study of the variation of splitting in the second heartbeat sound of
      wavelet transform.
AB  - The second heart sound, S2, consists of two acoustic components, A2 and P2. The
      former is due to the closure of the aortic valve and the latter is due to the
      closure of the pulmonary valve. The aortic valve usually closes before the
      pulmonary valve, introducing a time delay known as the 'split'. A technique based
      on discrete wavelet transform (DWT) and continuous wavelet transform (CWT) is
      developed in this paper to measure the split. To quantify splitting, two
      components in S2 (i.e. A2 and P2) are identified, and the delay between the two
      components can be estimated. One normal case and three pathological cases (mitral
      stenosis, pulmonary stenosis and atrial septal defect) are considered in this
      study. The split is measured for each S2 sound of the considered signals. The
      split normally varies in duration over the cardiac cycle. In certain pathologies
      such as ASD (atrial septal defect) or PS (pulmonary stenosis), the split becomes
      fixed over the cardiac cycle. The main part of this paper consists of the
      identification and measurement of the S2 split. The study confirms the notion of
      'variable splitting' for normal phonocardiogram and 'fixed splitting' for ASD and
      PS cases. This paper relates also to the establishment of statistical parameters
      to make a distinction between normal and pathological cases of phonocardiogram
      signals.

PMID- 16980285
TI  - Electric current perception of children: the role of age and gender.
AB  - Although it is widely accepted that children merit increased protection, little
      is known about the quantitative consequences of electric currents when setting
      safety limits. Measurements were performed on 240 children (117 girls and 123
      boys) older than 9 years. It was found that the electrosensitivity of children
      was higher than that of adults, but did not exceed the overall span of adult
      electrosensitivity. Girls' results depend only weakly on age. Therefore, no major
      change should be expected below the age of 9. The electrosensitivity of boys
      increases with decreasing age; however, it finally approaches and merges with
      that of girls. The results imply that the factor by which the allowed touch
      current should be reduced for children depends on the perception probability
      level considered. The reduction factor of 2, as chosen in the past, would need
      revision either in regard to its value or to the related perception probability
      level. If related to the still existing rationale for safety limits the factor
      would need to be far higher.

PMID- 16980286
TI  - Palm print image recovery and de-noising via multi-channel wavelet filter bank.
AB  - In this paper, a 3-channel wavelet transform method is introduced to recover palm
      print images following serious deformation. The deformation processing is
      actually a kind of digital re-sampling. A filter bank consisting of three filters
      is implemented for wavelet decomposition of the palm print image, and then a
      procedure of binary interpolation is performed after the image is reconstructed
      by another filter bank consisting of another three filters. The design of multi
      channel wavelet filter bank is based on the Quadrature Mirror Filter (QMF)
      method. Because the noise is caused by the Morie stripe, the images are further
      de-noised after the geometry deformation is addressed. Acceptable results have
      been obtained.

PMID- 16980287
TI  - Neural network-based prediction of missing key features in vertical GRF-time
      recordings.
AB  - Ground reaction force (GRF) time recordings are frequently corrupted due to
      faulty stepping on a force platform during gait, and this results in the loss of
      valuable data and the need for additional data acquisition. This paper proposes a
      new approach based on artificial neural networks for the estimation of lost key
      gait parameters using the available features of an affected GRF-time trace. GRF
      time plots were recorded using a force platform during normal walking of 14 young
      and 13 elderly individuals. Back-propagation neural network models were developed
      using features extracted from 466 vertical GRF-time characteristics that would be
      unaffected as inputs, and the likely affected gait features (e.g. stance time
      (ST), push-off force, (Fmax2) and push-off time (Tmax2)) as output. Performance
      of the models in predicting ST, Fmax2 and Tmax2 were tested using data from 30
      new gait trials. The neural network model predicted the missing STs with 96.5%
      (+/-2.6%) accuracy (r>0.9). Accuracy of the ST prediction deteriorated when push
      off force/time data were unavailable for the prediction model. Fmax2 and its time
      were reconstructed with an accuracy of 95.7% (+/-2.8%) and 97.6% (+/-1.7%)
      respectively. These results suggest that an artificial neural network may be
      applied to estimate missing ST, Fmax2 or Tmax2 information using features from an
      affected vertical GRF-time plot, and the method shows good promise for
      reconstructing gait forces from a corrupted force-time trace.

PMID- 16980288
TI  - Surface engineering of artificial heart valve disks using nanostructured thin
      films deposited by chemical vapour deposition and sol-gel methods.
AB  - Pyrolytic carbon (PyC) is widely used in manufacturing commercial artificial
      heart valve disks (HVD). Although PyC is commonly used in HVD, it is not the best
      material for this application since its blood compatibility is not ideal for
      prolonged clinical use. As a result thrombosis often occurs and the patients are
      required to take anti-coagulation drugs on a regular basis in order to minimize
      the formation of thrombosis. However, anti-coagulation therapy gives rise to some
      detrimental side effects in patients. Therefore, it is extremely urgent that
      newer and more technically advanced materials with better surface and bulk
      properties are developed. In this paper, we report the mechanical properties of
      PyC-HVD, i.e. strength, wear resistance and coefficient of friction. The strength
      of the material was assessed using Brinell indentation tests. Furthermore, wear
      resistance and coefficient of friction values were obtained from pin-on-disk
      testing. The micro-structural properties of PyC were characterized using XRD,
      Raman spectroscopy and SEM analysis. Also in this paper we report the preparation
      of freestanding nanocrystalline diamond films (FSND) using the time-modulated
      chemical vapour deposition (TMCVD) process. Furthermore, the sol-gel technique
      was used to uniformly coat PyC-HVD with dense, nanocrystalline-titanium oxide (nc
      TiO2) coatings. The as-grown nc-TiO2 coatings were characterized for
      microstructure using SEM and XRD analysis.

PMID- 16980289
TI  - ANN-based mapping of febrile subjects in mass thermogram screening: facts and
      myths.
AB  - Severe Acute Respiratory Syndrome (SARS) is a highly infectious disease caused by
      a coronavirus. Screening to detect potential SARS-infected subjects with elevated
      body temperature plays an important role in preventing the spread of SARS.
      Thermography is being used with ANN/AI to analyse the data collected from the
      designated SARS hospital in Singapore, and conclusive results are drawn. The
      current work evaluates the correlations (and classifications) between facial skin
      temperatures, including eye range and forehead, to aural temperature using a
      neural network (NN) approach, namely training backpropagation (BP) and Kohonen
      self-organizing map (SOM), to confirm the suitability of thermal imagers for
      human temperature screening. Both BP and SOM can form an opinion about the type
      of network that is better able to complement thermogram technology in fever
      diagnosis. This can produce better parameters for reducing the size of the NN
      classifier, while maintaining good classification accuracy. We observe that BP
      performs better than SOM NN. Confusion matrix (CM), an alternative display
      instrument, is able to process a high volume of input data and show the clustered
      output rapidly and accurately. The current research application will remain an
      interesting and useful reference for both local and overseas manufacturers of
      thermal scanners, users and various government and private establishments. As the
      elevation of body temperature is a common presenting symptom for many illnesses,
      including infectious diseases such as SARS, thermal imagers are useful and
      essential tools for mass screening of body temperature. This is true not only for
      SARS but also during other public health crises where widespread transmission of
      infection such as the danger of avian flu pandemic is a concern, in particular at
      places like hospitals and cross-border checkpoints.

PMID- 16980293
TI  - Comparative in vitro activities of tigecycline and 11 other antimicrobial agents
      against 215 epidemiologically defined multidrug-resistant Acinetobacter baumannii
      isolates.

PMID- 16980294
TI  - Comment on: immune reconstitution inflammatory syndrome: more answers, more
      questions.

PMID- 16980295
TI  - The replication factor C clamp loader requires arginine finger sensors to drive
      DNA binding and proliferating cell nuclear antigen loading.
AB  - Replication factor C (RFC) is an AAA+ heteropentamer that couples the energy of
      ATP binding and hydrolysis to the loading of the DNA polymerase processivity
      clamp, proliferating cell nuclear antigen (PCNA), onto DNA. RFC consists of five
      subunits in a spiral arrangement (RFC-A, -B, -C, -D, and -E, corresponding to
      subunits RFC1, RFC4, RFC3, RFC2, and RFC5, respectively). The RFC subunits are
      AAA+ family proteins and the complex contains four ATP sites (sites A, B, C, and
      D) located at subunit interfaces. In each ATP site, an arginine residue from one
      subunit is located near the gamma-phosphate of ATP bound in the adjacent subunit.
      These arginines act as "arginine fingers" that can potentially perform two
      functions: sensing that ATP is bound and catalyzing ATP hydrolysis. In this
      study, the arginine fingers in RFC were mutated to examine the steps in the PCNA
      loading mechanism that occur after RFC binds ATP. This report finds that the ATP
      sites of RFC function in distinct steps during loading of PCNA onto DNA. ATP
      binding to RFC powers recruitment and opening of PCNA and activates a gamma
      phosphate sensor in ATP site C that promotes DNA association. ATP hydrolysis in
      site D is uniquely stimulated by PCNA, and we propose that this event is coupled
      to PCNA closure around DNA, which starts an ordered hydrolysis around the ring.
      PCNA closure severs contact to RFC subunits D and E (RFC2 and RFC5), and the
      gamma-phosphate sensor of ATP site C is switched off, resulting in low affinity
      of RFC for DNA and ejection of RFC from the site of PCNA loading.

PMID- 16980296
TI  - Replication-dependent and -independent responses of RAD18 to DNA damage in human
      cells.
AB  - Postreplication repair facilitates tolerance of DNA damage during replication,
      overcoming termination of replication at sites of DNA damage. A major post
      replication repair pathway in mammalian cells is translesion synthesis, which is
      carried out by specialized polymerase(s), such as polymerase eta, and is
      identified by focus formation by the polymerase after irradiation with UVC light.
      The formation of these foci depends on RAD18, which ubiquitinates PCNA for the
      exchange of polymerases. To understand the initial processes in translesion
      synthesis, we have here analyzed the response to damage of RAD18 in human cells.
      We find that human RAD18 accumulates very rapidly and remains for a long period
      of time at sites of different types of DNA damage, including UVC light-induced
      lesions, and x-ray microbeam- and laser-induced single-strand breaks, in a cell
      cycle-independent manner. The accumulation of RAD18 at DNA damage is observed
      even when DNA replication is inhibited, and a small region containing a zinc
      finger motif located in the middle of RAD18 is essential and sufficient for the
      replication-independent damage accumulation. The zinc finger motif of RAD18 is
      not necessary for UV-induced polymerase eta focus formation, but another SAP (SAF
      A/B, Acinus and PIAS) motif near the zinc finger is required. These data indicate
      that RAD18 responds to DNA damage in two distinct ways, one replication-dependent
      and one replication-independent, involving the SAP and zinc finger motifs,
      respectively.

PMID- 16980297
TI  - Mdm2-mediated NEDD8 modification of TAp73 regulates its transactivation function.
AB  - Mutations in p73 are rare in cancer. Emerging evidence suggests that the relative
      expression of various p73 isoforms may contribute to tumorigenesis. Alternative
      promoters and N-terminal splicing result in the transcription and processing of
      either full-length (TA) or N-terminally truncated (deltaN) p73 isoforms. TAp73
      possesses pro-apoptotic functions, while deltaNp73 has anti-apoptotic properties
      via functional inhibition of TAp73 and p53. Here, we report that TAp73, but not
      deltaNp73, is covalently modified by NEDD8 under physiologic conditions in an
      Mdm2-dependent manner. Co-expression of NEDP1, a cysteine protease that
      specifically cleaves NEDD8 conjugates, was shown to deneddylate TAp73. In
      addition, blockage of the endogenous NEDD8 pathway increased TAp73-mediated
      transactivation of p53- and p73-responsive promoter-driven reporter activity, and
      in conjunction, neddylated TAp73 species were found preferentially in the
      cytoplasm. These results suggest that Mdm2 attenuates TAp73 transactivation
      function, at least in part, by promoting NEDD8-dependent TAp73 cytoplasmic
      localization and provide the first evidence of a covalent post-translational
      modification exclusively targeting the TA isoforms of p73.

PMID- 16980298
TI  - Knock-out mice reveal the contributions of P2Y and P2X receptors to nucleotide
      induced Ca2+ signaling in macrophages.
AB  - Immune cell function is modulated by changes in extracellular nucleotide levels.
      Here we used reverse transcription-PCR analyses, single cell Ca2+ imaging, and
      knock-out mice to define the receptors mediating nucleotide-induced Ca2+
      signaling in resident peritoneal macrophages. In Ca2+-free buffer, the potent
      (K0.5<1 microm) stimulatory effect of UTP (or ATP) on endoplasmic reticulum (ER)
      Ca2+ release was abolished in cells isolated from P2Y2/P2Y4 double knock-out
      mice. Moreover, P2Y4(0/-), but not P2Y2-/-, macrophages responded to UTP. In P2Y2
      /- macrophages, we could elicit Ca2+ responses to "pure" P2X receptor activation
      by applying ATP in buffer containing Ca2+. Purified UDP and ADP were ineffective
      agonists, although modest UDP-induced Ca2+ responses could be elicited in
      macrophages after "activation" with lipopolysaccharide and interferon-gamma.
      Notably, in Ca2+-free buffer, UTP-induced Ca2+ transients decayed within 1 min,
      and there was no response to repeated agonist challenge. Measurements of ER
      [Ca2+] with mag-fluo-4 showed that ER Ca2+ stores were depleted under these
      conditions. When extracellular Ca2+ was available, ER Ca2+ stores refilled, but
      Ca2+ increased to only approximately 40% of the initial value upon repeated UTP
      challenge. This apparent receptor desensitization persisted in GRK2+/- and GRK6-/
      macrophages and after inhibition of candidate kinases protein kinase C and
      calmodulin-dependent kinase II. Initial challenge with UTP also reduced Ca2+
      mobilization by complement component C5a (and vice versa). In conclusion,
      homologous receptor desensitization is not the major mechanism that rapidly
      dampens Ca2+ signaling mediated by P2Y2, the sole Gq-coupled receptor for UTP or
      ATP in macrophages. UDP responsiveness (P2Y6 receptor expression) increases
      following macrophage activation.

PMID- 16980299
TI  - The alpha-phosphoglucomutase of Lactococcus lactis is unrelated to the alpha-D
      phosphohexomutase superfamily and is encoded by the essential gene pgmH.
AB  - alpha-Phosphoglucomutase (alpha-PGM) plays an important role in carbohydrate
      metabolism by catalyzing the reversible conversion of alpha-glucose 1-phosphate
      to glucose 6-phosphate. Isolation of alpha-PGM activity from cell extracts of
      Lactococcus lactis strain MG1363 led to the conclusion that this activity is
      encoded by yfgH, herein renamed pgmH. Its gene product has no sequence homology
      to proteins in the alpha-d-phosphohexomutase superfamily and is instead related
      to the eukaryotic phosphomannomutases within the haloacid dehalogenase
      superfamily. In contrast to known bacterial alpha-PGMs, this 28-kDa enzyme is
      highly specific for alpha-glucose 1-phosphate and glucose 6-phosphate and showed
      no activity for mannose phosphate. To elucidate the function of pgmH, the
      metabolism of glucose and galactose was characterized in mutants overproducing or
      with a deficiency of alpha-PGM activity. Overproduction of alpha-PGM led to
      increased glycolytic flux and growth rate on galactose. Despite several attempts,
      we failed to obtain a deletion mutant of pgmH. The essentiality of this gene was
      proven by using a conditional knock-out strain in which a native copy of the gene
      was provided in trans under the control of the nisin promoter. Growth of this
      strain was severely impaired when alpha-PGM activity was below the control level.
      We show that the novel L. lactis alpha-PGM is the only enzyme that mediates the
      interconversion of alpha-glucose 1-phosphate to glucose 6-phosphate and is
      essential for growth.

PMID- 16980300
TI  - Molecular heterosis of prion protein beta-oligomers. A potential mechanism of
      human resistance to disease.
AB  - The gene encoding prion protein is polymorphic in human populations, with over
      40% of native Europeans, for example, being heterozygous for the Met-129 and Val
      129 alleles. The polymorphism affects both the incidence and the clinical
      presentation of a range of prion diseases, with heterozygotes generally showing
      the highest levels of resistance. It has been suggested that an earlier epidemic
      of prion diseases exerted balancing selection on the two alleles, and we have
      previously demonstrated that the two encoded proteins have potentially
      compensating tendencies to form amyloid and soluble beta-oligomers, respectively,
      in vitro. More strikingly, here we demonstrate that mixed oligomers, composed of
      both allelic forms, show an extreme sluggishness in converting to amyloid in
      comparison with oligomers homogenous for either allele. It may be that this
      example of molecular heterosis in vitro provides the basis for maintenance of the
      polymorphism in the population and that beta-oligomers represent a form of PrP
      sequestered from pathogenic amyloid formation in vivo.

PMID- 16980301
TI  - Arrestin-2 and G protein-coupled receptor kinase 5 interact with NFkappaB1 p105
      and negatively regulate lipopolysaccharide-stimulated ERK1/2 activation in
      macrophages.
AB  - Toll-like receptors (TLRs) are a recently described receptor class involved in
      the regulation of innate and adaptive immunity. Here, we demonstrate that
      arrestin-2 and GRK5 (G protein-coupled receptor kinase 5), proteins that regulate
      G protein-coupled receptor signaling, play a negative role in TLR4 signaling in
      Raw264.7 macrophages. We find that lipopolysaccharide (LPS)-induced ERK1/2
      phosphorylation is significantly enhanced in arrestin-2 and GRK5 knockdown cells.
      To elucidate the mechanisms involved, we tested the effect of arrestin-2 and GRK5
      knockdown on LPS-stimulated signaling components that are upstream of ERK
      phosphorylation. Upon LPS stimulation, IkappaB kinase promotes phosphorylation
      and degradation of NFkappaB1 p105 (p105), which releases TPL2 (a MAP3K), which
      phosphorylates MEK1/2, which in turn phosphorylates ERK1/2. We demonstrate that
      knockdown of arrestin-2 leads to enhanced LPS-induced phosphorylation and
      degradation of p105, enhanced TPL2 release, and enhanced MEK1/2 phosphorylation.
      GRK5 knockdown also results in enhanced IkappaB kinase-mediated p105
      phosphorylation and degradation, whereas GRK2 and GRK6 knockdown have no effect
      on this pathway. In vitro analysis demonstrates that arrestin-2 directly binds to
      the COOH-terminal domain of p105, whereas GRK5 binds to and phosphorylates p105.
      Taken together, these results suggest that p105 phosphorylation by GRK5 and
      binding of arrestin-2 negatively regulates LPS-stimulated ERK activation. These
      results reveal that arrestin-2 and GRK5 are important negative regulatory
      components in TLR4 signaling.

PMID- 16980302
TI  - Fluorometric measurements of intermolecular distances between the alpha- and beta
      subunits of the Na+/K+-ATPase.
AB  - The Na+/K+-ATPase maintains the physiological Na+ and K+ gradients across the
      plasma membrane in most animal cells. The functional unit of the ion pump is
      comprised of two mandatory subunits including the alpha-subunit, which mediates
      ATP hydrolysis and ion translocation, as well as the beta-subunit, which acts as
      a chaperone to promote proper membrane insertion and trafficking in the plasma
      membrane. To examine the conformational dynamics between the alpha- and beta
      subunits of the Na+/K+-ATPase during ion transport, we have used fluorescence
      resonance energy transfer, under voltage clamp conditions on Xenopus laevis
      oocytes, to differentiate between two models that have been proposed for the
      relative orientation of the alpha- and beta-subunits. These experiments were
      performed by measuring the time constant of irreversible donor fluorophore
      destruction with fluorescein-5-maleimide as the donor fluorophore and in the
      presence or absence of tetramethylrhodamine-6-maleimide as the acceptor
      fluorophore following labeling on the M3-M4 or M5-M6 loop of the alpha-subunit
      and the beta-subunit. We have also used fluorescence resonance energy transfer to
      investigate the relative movement between the two subunits as the ion pump
      shuttles between the two main conformational states (E1 and E2) as described by
      the Albers-Post scheme. The results from this study have identified a model for
      the orientation of the beta-subunit in relation to the alpha-subunit and suggest
      that the alpha- and beta-subunits move toward each other during the E2 to E1
      conformational transition.

PMID- 16980303
TI  - An exonic splicing silencer is involved in the regulated splicing of glucose 6
      phosphate dehydrogenase mRNA.
AB  - The inhibition of glucose-6-phosphate dehydrogenase (G6PD) expression by
      arachidonic acid occurs by changes in the rate of pre-mRNA splicing. Here, we
      have identified a cis-acting RNA element required for regulated splicing of G6PD
      mRNA. Using transfection of G6PD RNA reporter constructs into rat hepatocytes,
      the cis-acting RNA element involved in this regulation was localized to
      nucleotides 43-72 of exon 12 in the G6PD mRNA. In in vitro splicing assays, RNA
      substrates containing exon 12 were not spliced. In contrast, RNA substrates
      containing other regions (exons 8 and 9 or exons 10 and 11) of the G6PD mRNA were
      efficiently spliced. Furthermore, exon 12 can inhibit splicing when substituted
      for other exons in RNA substrates that are readily spliced. This activity of the
      exon 12 regulatory element suggests that it is an exonic splicing silencer.
      Consistent with its activity as a splicing silencer, spliceosome assembly was
      inhibited on RNA substrates containing exon 12 compared with RNAs representing
      other regions of the G6PD transcript. Elimination of nucleotides 43-72 of exon 12
      did not restore splicing of exon 12-containing RNA; thus, the 30-nucleotide
      element may not be exclusively a silencer. The binding of heterogeneous nuclear
      ribonucleoproteins K, L, and A2/B1 from both HeLa and hepatocyte nuclear extracts
      to the element further supports its activity as a silencer. In addition, SR
      proteins bind to the element, consistent with the presence of enhancer activity
      within this sequence. Thus, an exonic splicing silencer is involved in the
      inhibition of splicing of a constitutively spliced exon in the G6PD mRNA.

PMID- 16980304
TI  - S-nitrosylation of Bcl-2 inhibits its ubiquitin-proteasomal degradation. A novel
      antiapoptotic mechanism that suppresses apoptosis.
AB  - Bcl-2 is a key apoptosis regulatory protein of the mitochondrial death pathway
      whose function is dependent on its expression levels. Although Bcl-2 expression
      is controlled by various mechanisms, post-translational modifications, such as
      ubiquitination and proteasomal degradation, have emerged as important regulators
      of Bcl-2 function. However, the underlying mechanisms of this regulation are
      unclear. We report here that Bcl-2 undergoes S-nitrosylation by endogenous nitric
      oxide (NO) in response to multiple apoptotic mediators and that this modification
      inhibits ubiquitin-proteasomal degradation of Bcl-2. Inhibition of NO production
      by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3
      oxide and by NO synthase inhibitor aminoguanidine effectively inhibited S
      nitrosylation of Bcl-2, increased its ubiquitination, and promoted apoptotic cell
      death induced by chromium (VI). In contrast, the NO donors dipropylenetriamine
      NONOate and sodium nitroprusside showed opposite effects. The effect of NO on Bcl
      2 stability was shown to be independent of its dephosphorylation. Mutational
      analysis of Bcl-2 further showed that the two cysteine residues of Bcl-2 (Cys158
      and Cys229) are important in the S-nitrosylation process and that mutations of
      these cysteines completely inhibited Bcl-2 S-nitrosylation. Treatment of the
      cells with other stress inducers, including Fas ligand and buthionine sulfoxide,
      also induced Bcl-2 S-nitrosylation, suggesting that this is a general phenomenon
      that regulates Bcl-2 stability and function under various stress conditions.
      These findings indicate a novel function of NO and its regulation of Bcl-2, which
      provides a key mechanism for the control of apoptotic cell death and cancer
      development.

PMID- 16980305
TI  - Alpha-actinin 4 potentiates myocyte enhancer factor-2 transcription activity by
      antagonizing histone deacetylase 7.
AB  - Histone deacetylase 7 (HDAC7) is a member of class IIa HDACs that regulate
      myocyte enhancer factor-2 (MEF2)-mediated transcription and participate in
      multiple cellular processes such as T cell apoptosis. We have identified alpha
      actinin 1 and 4 as class IIa HDAC-interacting proteins. The interaction domains
      are mapped to C terminus of alpha-actinin 4 and amino acids 72-172 of HDAC7. A
      point mutation in HDAC7 that disrupts its association with MEF2A also disrupts
      its association with alpha-actinin 4, indicating that MEF2A and alpha-actinin 4
      binding sites largely overlap. We have also isolated a novel splice variant of
      alpha-actinin 4 that is predominantly localized in the nucleus, a pattern
      distinct from the full-length alpha-actinin 4, which is primarily distributed in
      the cytoplasm and plasma membrane. Using small interfering RNA, chromatin
      immunoprecipitation, and transient transfection assays, we show that alpha
      actinin 4 potentiates expression of TAF55, a putative MEF2 target gene. Loss of
      MEF2A interaction correlates with loss of the ability of alpha-actinin 4 to
      potentiate TAF55 promoter activity. Ectopic expression of alpha-actinin 4, but
      not the mutant defective in MEF2A association, leads to disruption of HDAC7.MEF2A
      association and enhancement of MEF2-mediated transcription. Taken together, we
      have identified a novel mechanism by which HDAC7 activity is negatively regulated
      and uncovered a previously unknown function of alpha-actinin 4.

PMID- 16980306
TI  - Evidence for a matriptase-prostasin proteolytic cascade regulating terminal
      epidermal differentiation.
AB  - Recent gene ablation studies in mice have shown that matriptase, a type II
      transmembrane serine protease, and prostasin, a glycosylphosphatidylinositol
      anchored membrane serine protease, are both required for processing of the
      epidermis-specific polyprotein, profilaggrin, stratum corneum formation, and
      acquisition of epidermal barrier function. Here we present evidence that
      matriptase acts upstream of prostasin in a zymogen activation cascade that
      regulates terminal epidermal differentiation and is required for prostasin
      zymogen activation. Enzymatic gene trapping of matriptase combined with prostasin
      immunohistochemistry revealed that matriptase was co-localized with prostasin in
      transitional layer cells of the epidermis and that the developmental onset of
      expression of the two membrane proteases was coordinated and correlated with
      acquisition of epidermal barrier function. Purified soluble matriptase
      efficiently converted soluble prostasin zymogen to an active two-chain form that
      formed SDS-stable complexes with the serpin protease nexin-1. Whereas two forms
      of prostasin with molecular weights corresponding to the prostasin zymogen and
      active prostasin were present in wild type epidermis, prostasin was exclusively
      found in the zymogen form in matriptase-deficient epidermis. These data suggest
      that matriptase, an autoactivating protease, acts upstream from prostasin to
      initiate a zymogen cascade that is essential for epidermal differentiation.

PMID- 16980307
TI  - A novel class of vascular endothelial growth factor-responsive genes that require
      forkhead activity for expression.
AB  - Recently, we have shown that transient phosphorylation and inhibition of the pro
      apoptotic transcription factor, forkhead, by vascular endothelial growth factor
      (VEGF) is essential for endothelial cell (EC) survival and proliferation. The
      goal of the present study was to determine whether forkhead (FKHR) also plays a
      positive role in agonist-mediated gene induction. Human coronary artery ECs were
      transduced with adenovirus overexpressing constitutively active phosphorylation
      resistant triple mutant FKHR or transfected with small interference RNA (siRNA)
      against FKHR. The cells were then treated in the absence or presence of VEGF and
      assayed for gene expression using quantitative real-time PCR and Northern blots
      analyses. The data revealed a novel set of VEGF-responsive genes that require
      FKHR activity for optimal expression in ECs, including bone morphogenic protein
      2, cbp/p300-interacting transactivator 2, decay accelerating factor (DAF),
      vascular cell adhesion molecule-1 (VCAM-1), manganese superoxide dismutase,
      endothelial-specific molecule-1, RING1 and YY1-binding protein, and matrix
      metalloproteinase-10. Consistent with a positive role for FKHR in mediating VEGF
      induction of DAF and VCAM-1 mRNA, siRNA against FKHR attenuated the effect of
      VEGF on complement-mediated EC lysis and monocyte adhesion, respectively. VEGF
      induction of the forkhead-dependent genes was down-regulated by the NF-kappaB
      inhibitor, constitutively active Ad-IkappaB, and in some cases by the nuclear
      factor of activated T-cells (NF-AT) inhibitor, cyclosporin. Together, these
      findings suggest that the VEGF-forkhead signaling axis plays an important
      functional role in ECs beyond the regulation of cell survival/apoptosis and cell
      cycle.

PMID- 16980308
TI  - The inhibition of mitochondrial complex I (NADH:ubiquinone oxidoreductase) by
      Zn2+.
AB  - NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria is a
      highly complicated, membrane-bound enzyme. It is central to energy transduction,
      an important source of cellular reactive oxygen species, and its dysfunction is
      implicated in neurodegenerative and muscular diseases and in aging. Here, we
      describe the effects of Zn2+ on complex I to define whether complex I may
      contribute to mediating the pathological effects of zinc in states such as
      ischemia and to determine how Zn2+ can be used to probe the mechanism of complex
      I. Zn2+ inhibits complex I more strongly than Mg2+, Ca2+, Ba2+, and Mn2+ to Cu2+
      or Cd2+. It does not inhibit NADH oxidation or intramolecular electron transfer,
      so it probably inhibits either proton transfer to bound quinone or proton
      translocation. Thus, zinc represents a new class of complex I inhibitor clearly
      distinct from the many ubiquinone site inhibitors. No evidence for increased
      superoxide production by zinc-inhibited complex I was detected. Zinc binding to
      complex I is mechanistically complicated. During catalysis, zinc binds slowly and
      progressively, but it binds rapidly and tightly to the resting state(s) of the
      enzyme. Reactivation of the inhibited enzyme upon the addition of EDTA is slow,
      and inhibition is only partially reversible. The IC50 value for the Zn2+
      inhibition of complex I is high (10-50 microm, depending on the enzyme state);
      therefore, complex I is unlikely to be a major site for zinc inhibition of the
      electron transport chain. However, the slow response of complex I to a change in
      Zn2+ concentration may enhance any physiological consequences.

PMID- 16980310
TI  - Elafin prevents lipopolysaccharide-induced AP-1 and NF-kappaB activation via an
      effect on the ubiquitin-proteasome pathway.
AB  - The serine anti-protease elafin is expressed by monocytes, alveolar macrophages,
      neutrophils, and at mucosal surfaces and possesses antimicrobial activity. It is
      also known to reduce lipopolysaccharide-induced neutrophil influx into murine
      alveoli as well as to abrogate lipopolysaccharide-induced production of matrix
      metalloprotease 9, macrophage inhibitory protein 2, and tumor necrosis factor
      alpha by as-yet unidentified mechanisms. In this report we have shown that elafin
      inhibits the lipopolysaccharide-induced production of monocyte chemoattractant
      protein-1 in monocytes by inhibiting AP-1 and NF-kappaB activation. Elafin
      prevented lipopolysaccharide-induced phosphorylation of AP-1, c-Jun, and JNK but
      had no effect on phosphorylation of p38. The lipopolysaccharide-induced
      degradation of IL-1R-associated kinase 1, IkappaBalpha, and IkappaBbeta was
      inhibited by elafin but phosphorylation of IkappaBalpha was unaffected.
      Polyubiquitinated protein including polyubiquitinated IkappaBalpha was shown to
      accumulate in the presence of elafin. These results suggest that inhibition by
      elafin of lipopolysaccharide-induced AP-1 and NF-kappaB activation occurs via an
      effect on the ubiquitin-proteasome pathway.

PMID- 16980309
TI  - Loss of CNGB1 protein leads to olfactory dysfunction and subciliary cyclic
      nucleotide-gated channel trapping.
AB  - Olfactory receptor neurons (ORNs) employ a cyclic nucleotide-gated (CNG) channel
      to generate a receptor current in response to an odorant-induced rise in cAMP.
      This channel contains three types of subunits, the principal CNGA2 subunit and
      two modulatory subunits (CNGA4 and CNGB1b). Here, we have analyzed the functional
      relevance of CNGB1 for olfaction by gene targeting in mice. Electro-olfactogram
      responses of CNGB1-deficient (CNGB1-/-) mice displayed a reduced maximal
      amplitude and decelerated onset and recovery kinetics compared with wild-type
      mice. In a behavioral test, CNGB1-/- mice exhibited a profoundly decreased
      olfactory performance. Electrophysiological recordings revealed that ORNs of
      CNGB1-/- mice weakly expressed a CNG current with decreased cAMP sensitivity,
      very rapid flicker-gating behavior and no fast modulation by Ca2+-calmodulin. Co
      immunoprecipitation confirmed the presence of a CNGA2/CNGA4 channel in the
      olfactory epithelium of CNGB1-/- mice. This CNGA2/CNGA4 channel was targeted to
      the plasma membrane of olfactory knobs, but failed to be trafficked into
      olfactory cilia. Interestingly, we observed a similar trafficking defect in mice
      deficient for the CNGA4 subunit. In conclusion, these results demonstrate that
      CNGB1 has a dual function in vivo. First, it endows the olfactory CNG channel
      with a variety of biophysical properties tailored to the specific requirements of
      olfactory transduction. Second, together with the CNGA4 subunit, CNGB1 is needed
      for ciliary targeting of the olfactory CNG channel.

PMID- 16980311
TI  - Nicotiana tabacum osmotic stress-activated kinase is regulated by phosphorylation
      on Ser-154 and Ser-158 in the kinase activation loop.
AB  - NtOSAK (Nicotiana tabacum osmotic stress-activated protein kinase), a member of
      the SnRK2 subfamily, is activated rapidly in response to hyperosmotic stress. Our
      previous results as well as data presented by others indicate that
      phosphorylation is involved in activation of SnRK2 kinases. Here, we have mapped
      the regulatory phosphorylation sites of NtOSAK by mass spectrometry with
      collision-induced peptide fragmentation. We show that active NtOSAK, isolated
      from NaCl-treated tobacco BY-2 cells, is phosphorylated on Ser-154 and Ser-158 in
      the kinase activation loop. Prediction of the NtOSAK three-dimensional structure
      indicates that phosphorylation of Ser-154 and Ser-158 triggers changes in enzyme
      conformation resulting in its activation. The involvement of Ser-154 and Ser-158
      phosphorylation in regulation of NtOSAK activity was confirmed by site-directed
      mutagenesis of NtOSAK expressed in bacteria and in maize protoplasts. Our data
      reveal that phosphorylation of Ser-158 is essential for NtOSAK activation,
      whereas phosphorylation of Ser-154 most probably facilitates Ser-158
      phosphorylation. The time course of NtOSAK phosphorylation on Ser-154 and Ser-158
      in BY-2 cells subjected to osmotic stress correlates with NtOSAK activity,
      indicating that NtOSAK is regulated by reversible phosphorylation of these
      residues in vivo. Importantly, Ser-154 and Ser-158 are conserved in all SnRK2
      subfamily members, suggesting that phosphorylation at these sites may be a
      general mechanism for SnRK2 activation.

PMID- 16980312
TI  - Cytogenetic and molecular biomonitoring of a Portuguese population exposed to
      pesticides.
AB  - Widespread use of pesticides in agriculture represents a threat not only to the
      environment but also to human populations exposed to them. Many of these
      compounds are capable of inducing mutations in DNA and lead to several diseases
      including cancer. In the present study, cytogenetic damage in peripheral
      lymphocytes from 33 farmers of Oporto district (Portugal) exposed to pesticides
      was evaluated by means of micronuclei (MN), sister chromatid exchange (SCE) and
      chromosomal aberrations (CA). In addition, effect of polymorphic genes of
      xenobiotic metabolizing enzymes (GSTM1, GSTT1, GSTP1, CYP2E1 and EPHX1) was also
      evaluated. A non-exposed group from the same area and with same demographic
      characteristics without exposure to genotoxic compounds was studied and data
      obtained from both groups was compared. MN and SCE frequencies were significantly
      higher in the exposed group (P < 0.005). In what concerns CA results, no
      significant differences were observed. It was possible to relate a specific
      working environment (greenhouses) with higher levels of genetic damage. Use of
      personal protective equipment revealed to be important to prevent exposure and
      diminish genetic damage inflicted by pesticides. Allele frequencies of studied
      polymorphic genes obtained in this study are similar to the ones described by
      other authors for Caucasian populations. Despite the low number of subjects,
      results suggest that low mEH (microsomal epoxide hydrolase) activity as well as
      GSTT1 positive genotype are associated with increased cytogenetic damage.

PMID- 16980313
TI  - Commentary: do older men and women gain equally from improving childhood
      conditions?

PMID- 16980314
TI  - Effects of calcium supplementation on bone density in healthy children: meta
      analysis of randomised controlled trials.
AB  - OBJECTIVES: To assess the effectiveness of calcium supplementation for improving
      bone mineral density in healthy children and to determine if any effect is
      modified by other factors and persists after supplementation stops. DESIGN: Meta
      analysis. DATA SOURCES: Electronic bibliographic databases, hand searching of
      conference proceedings, and contacting authors for unpublished data. REVIEW
      METHODS: We included randomised placebo controlled trials of calcium
      supplementation in healthy children that lasted at least three months and had
      bone outcomes measured after at least six months of follow-up. Two reviewers
      independently extracted data and assessed quality. Meta-analyses predominantly
      used fixed effects models with outcomes given as standardised mean differences.
      RESULTS: We included 19 studies involving 2859 children. Calcium supplementation
      had no effect on bone mineral density at the femoral neck or lumbar spine. There
      was a small effect on total body bone mineral content (standardised mean
      difference 0.14, 95% confidence interval 0.01 to 0.27) and upper limb bone
      mineral density (0.14, 0.04 to 0.24). This effect persisted after the end of
      supplementation only at the upper limb (0.14, 0.01 to 0.28). There was no
      evidence that sex, baseline calcium intake, pubertal stage, ethnicity, or level
      of physical activity modified the effect. CONCLUSIONS: The small effect of
      calcium supplementation on bone mineral density in the upper limb is unlikely to
      reduce the risk of fracture, either in childhood or later life, to a degree of
      major public health importance.

PMID- 16980315
TI  - A randomised controlled trial of acupuncture care for persistent low back pain:
      cost effectiveness analysis.
AB  - OBJECTIVE: To evaluate the cost effectiveness of acupuncture in the management of
      persistent non-specific low back pain. DESIGN: Cost effectiveness analysis of a
      randomised controlled trial. SETTING: Three private acupuncture clinics and 18
      general practices in York, England. PARTICIPANTS: 241 adults aged 18-65 with non
      specific low back pain of 4-52 weeks' duration. INTERVENTIONS: Ten individualised
      acupuncture treatments over three months from acupuncturists trained in
      traditional Chinese medicine (n = 160) or usual care only (n = 81). MAIN OUTCOME
      MEASURE: Incremental cost per quality adjusted life year (QALY) gained over two
      years. RESULTS: Total costs to the United Kingdom's health service during the two
      year study period were higher on average for the acupuncture group (460 pounds
      sterling; 673 euros; 859 dollars) than for the usual care group (345 pounds
      sterling) because of the costs associated with initial treatment. The mean
      incremental health gain from acupuncture at 12 months was 0.012 QALYs (95%
      confidence interval -0.033 to 0.058) and at 24 months was 0.027 QALYs (-0.056 to
      0.110), leading to a base case estimate of 4241 pounds sterling per QALY gained.
      This result was robust to sensitivity analysis. The probabilistic sensitivity
      analysis showed acupuncture to have a more than 90% chance of being cost
      effective at a pound20 000 cost per QALY threshold. CONCLUSION: A short course of
      traditional acupuncture for persistent non-specific low back pain in primary care
      confers a modest health benefit for minor extra cost to the NHS compared with
      usual care. Acupuncture care for low back pain seems to be cost effective in the
      longer term. TRIAL REGISTRATION: ISRCTN80764175 [controlled-trials.com].

PMID- 16980317
TI  - Simple histone acetylation plays a complex role in the regulation of gene
      expression.
AB  - Eukaryotic DNA is packaged into chromatin by histone proteins, which assemble the
      DNA into an organized, higher-order structure. The precise organization of
      chromatin is essential for faithful execution of DNA-mediated reactions such as
      transcription, DNA replication, DNA repair and DNA recombination. The
      organization of chromatin is considered to be regulated by a variety of post
      translational modifications of histones, such as acetylation, methylation,
      phosphorylation, ubiquitination, SUMOylation and poly-ADP-ribosylation. The
      relationship between histone acetylation and gene expression was first observed
      in 1964. Since then, a great deal of evidence has accumulated showing that not
      only transcription but other DNA-mediated reactions also are regulated by histone
      acetylation. With regard to the putative mechanism(s) by which histone
      acetylation regulates the flow of genetic information, site-specific modification
      and recognition of acetylated histone/DNA complexes have been postulated.
      Elucidation of the downstream effects of histone modification, as well as the
      identification, isolation and characterization of the relevant factors involved,
      have aided in our understanding of the mechanisms of regulation of DNA activity
      by histones. Currently, state-of-the-art technologies that enable genome-wide
      analysis are allowing insight into a critical and interesting question in
      eukaryotic transcription: are the principles that govern transcription of
      individual gene loci applicable to the genome as a whole? Here, we review the
      recent progress on histone modifications, with an emphasis on the role of histone
      acetylation in gene expression.

PMID- 16980316
TI  - Randomised controlled trial of a short course of traditional acupuncture compared
      with usual care for persistent non-specific low back pain.
AB  - OBJECTIVE: To determine whether a short course of traditional acupuncture
      improves longer term outcomes for patients with persistent non-specific low back
      pain in primary care. DESIGN: Pragmatic, open, randomised controlled trial.
      SETTING: Three private acupuncture clinics and 18 general practices in York,
      England. PARTICIPANTS: 241 adults aged 18-65 with non-specific low back pain of 4
      52 weeks' duration. INTERVENTIONS: 10 individualised acupuncture treatments from
      one of six qualified acupuncturists (160 patients) or usual care only (81
      patients). MAIN OUTCOME MEASURES: The primary outcome was SF-36 bodily pain,
      measured at 12 and 24 months. Other outcomes included reported use of analgesics,
      scores on the Oswestry pain disability index, safety, and patient satisfaction.
      RESULTS: 39 general practitioners referred 289 patients of whom 241 were
      randomised. At 12 months average SF-36 pain scores increased by 33.2 to 64.0 in
      the acupuncture group and by 27.9 to 58.3 in the control group. Adjusting for
      baseline score and for any clustering by acupuncturist, the estimated
      intervention effect was 5.6 points (95% confidence interval -0.2 to 11.4) at 12
      months (n = 213) and 8.0 points (2.8 to 13.2) at 24 months (n = 182). The
      magnitude of the difference between the groups was about 10%-15% of the final
      pain score in the control group. Functional disability was not improved. No
      serious or life threatening events were reported. CONCLUSIONS: Weak evidence was
      found of an effect of acupuncture on persistent non-specific low back pain at 12
      months, but stronger evidence of a small benefit at 24 months. Referral to a
      qualified traditional acupuncturist for a short course of treatment seems safe
      and acceptable to patients with low back pain. TRIAL REGISTRATION: ISRCTN80764175
      [controlled-trials.com].

PMID- 16980318
TI  - Comparison of the effects of exposure to light in Harshaw LiF:Mg,Ti and
      LiF:Mg,Cu,P.
AB  - The response of thermoluminescence dosemeters (TLDs) to light, in various
      conditions, has been studied. TLD cards containing both conventional lithium
      fluoride (LiF:Mg,Ti) and the high-sensitivity material LiF:Mg,Cu,P were
      available, so permitting a comparison between the two types. Also available for
      the tests were Harshaw extremity EXT-RAD (LiF:Mg,Cu,P) dosemeters. The LiF:Mg,Ti
      body TLD cards and the EXT-RAD extremity dosemeters both showed some response to
      fluorescent light, while the LiF:Mg,Cu,P cards showed no significant response. It
      is therefore concluded that LiF:Mg,Cu,P body cards need no special precautions to
      protect them from the effects of light. For LiF:Mg,Ti cards and extremity
      dosemeters, effects are small, but steps to avoid excessive light exposure should
      be considered.

PMID- 16980319
TI  - Overview of active personal dosemeters for individual monitoring in the European
      Union.
AB  - In 2001, the European Radiation Dosimetry Group, EURADOS, started a working group
      on 'Harmonisation of Individual Monitoring in Europe and the Dissemination of
      Information on New Techniques in this Field'. Within this group, one of the
      projects consisted of analysing the status of active personal dosemeters (APDs)
      in Europe. This paper reviews the regulatory requirements for APDs in 15 EU
      member states and summarises the main characteristics of commercial and new
      developments in this field. In particular, it focuses on the comparison of APD
      performance and standard passive dosimetry systems. Based on this information, an
      evaluation is initiated to establish why several countries are reluctant to
      accept APDs for dose records.

PMID- 16980320
TI  - CisView: a browser and database of cis-regulatory modules predicted in the mouse
      genome.
AB  - To facilitate the analysis of gene regulatory regions of the mouse genome, we
      developed a CisView (http://lgsun.grc.nia.nih.gov/cisview), a browser and
      database of genome-wide potential transcription factor binding sites (TFBSs) that
      were identified using 134 position-weight matrices and 219 sequence patterns from
      various sources and were presented with the information about sequence
      conservation, neighboring genes and their structures, GO annotations, protein
      domains, DNA repeats and CpG islands. Analysis of the distribution of TFBSs
      revealed that many TFBSs (N = 145) were over-represented near transcription start
      sites. We also identified potential cis-regulatory modules (CRMs) defined as
      clusters of conserved TFBSs in the entire mouse genome. Out of 739 074 CRMs, 157
      442 had a significantly higher regulatory potential score than semi-random
      sequences generated with a 3rd-order Markov process. The CisView browser provides
      a user-friendly computer environment for studying transcription regulation on a
      whole-genome scale and can also be used for interpreting microarray experiments
      and identifying putative targets of transcription factors.

PMID- 16980321
TI  - Acute renal failure during pregnancy--an unusual cause.

PMID- 16980322
TI  - Renal histology in Chinese patients with anti-myeloperoxidase autoantibody
      positive Wegener's granulomatosis.
AB  - BACKGROUND: Proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA) was the
      serological marker for Wegener's granulomatosis (WG), while myeloperoxidase (MPO)
      ANCA was the serological marker for microscopic polyangiitis (MPA). However, our
      previous study suggested that patients with MPO-ANCA positive WG were common in
      Chinese. This study aimed to analyse the renal histology of patients with MPO
      ANCA positive WG. METHODS: Patients in our centre with WG were selected according
      to both the Chapel Hill Consensus Conference (CHCC) definition and American
      College of Rheumatology classification criteria. Patients with MPA were selected
      according to the CHCC definition. The renal histology was compared between
      patients with MPO-ANCA positive WG and with PR3-ANCA positive WG as well as
      patients with MPO-ANCA positive MPA. RESULTS: Sixty-one patients with WG had
      complete renal histological data, 39/61 with positive MPO-ANCA and 22/61 with
      positive PR3-ANCA. Among patients with crescents in glomeruli, those with MPO
      ANCA had fewer cellular crescents and more fibrous crescents than those with PR3
      ANCA (P < 0.01 and P < 0.05, respectively). Interstitial fibrosis and tubular
      atrophy were more prevalent and severe in patients with MPO-ANCA than in those
      with PR3-ANCA (P < 0.01 and P < 0.05, respectively). Compared with 44 patients
      with MPO-ANCA positive MPA, patients with MPO-ANCA positive WG had fewer
      glomeruli with crescents and more normal glomeruli (P < 0.01 and P < 0.01,
      respectively). CONCLUSION: Patients with MPO-ANCA positive WG are common in
      Chinese. In renal histology, chronic lesions were more severe and prevalent in
      patients with MPO-ANCA positive WG than in patients with PR3-ANCA positive WG.
      Glomerular lesions were less severe and less prevalent in patients with MPO-ANCA
      positive WG than in those with MPO-ANCA positive MPA.

PMID- 16980323
TI  - Unexpected rate of severe leucopenia with the association of mycophenolate
      mofetil and valganciclovir in kidney transplant recipients.

PMID- 16980324
TI  - IgA nephritis: ACE inhibitors, steroids, both or neither?

PMID- 16980325
TI  - An unusual case of CAPD-related peritonitis associated with fallopian tube
      capture of a CAPD catheter.

PMID- 16980326
TI  - Optimized extraction of glycosaminoglycans from normal and osteoarthritic
      cartilage for glycomics profiling.
AB  - Articular cartilage is a highly specialized smooth connective tissue whose proper
      functioning depends on the maintenance of an extracellular matrix consisting of
      an integrated assembly of collagens, glycoproteins, proteoglycans (PG), and
      glycosaminoglycans. Isomeric chondroitin sulfate glycoforms differing in position
      and degree of sulfation and uronic acid epimerization play specific and distinct
      functional roles during development and disease onset. This work introduces a
      novel glycosaminoglycan extraction method for the quantification of mixtures of
      chondroitin sulfate oligosaccharides from intact cartilage tissue for mass
      spectral analysis. Glycosaminoglycans were extracted from intact cartilage
      samples using a combination of ethanol precipitation and enzymatic release
      followed by reversed-phase and strong anion exchange solid-phase extraction
      steps. Extracted chondroitin sulfate glycosaminoglycans were partially
      depolymerized using chondroitinases, labeled with 2-anthranilic acid-d(4) (2-AA)
      and subjected to size exclusion chromatography with online electrospray
      ionization mass spectrometric detection in the negative ion mode. The method
      presented herein enabled simultaneous determination of sulfate position and
      uronic acid epimerization in juvenile bovine and adult human cartilage samples.
      The method was applied to a series of 13 adult human cartilage explants. Standard
      deviation of the mean for the measurements was 1.6 on average. Coefficients of
      variation were approximately 4% for all compositions of 40% or greater. These
      results show that the new method has sufficient accuracy to allow determination
      of topographical distribution of glycoforms in connective tissue.

PMID- 16980327
TI  - Major O-glycans in the spores of two microsporidian parasites are represented by
      unbranched manno-oligosaccharides containing alpha-1,2 linkages.
AB  - Protein glycosylation in microsporidia, a fungi-related group comprising
      exclusively obligate intracellular parasitic species, is still poorly documented.
      Here, we have studied glycoconjugate localization and glycan structures in spores
      of Encephalitozoon cuniculi and Antonospora locustae, two distantly related
      microsporidians invading mammalian and insect hosts, respectively. The polar sac
      anchoring disc complex or polar cap, an apical element of the sporal invasion
      apparatus, was strongly periodic acid-thiocarbohydrazide-Ag proteinate-positive.
      Mannose-binding lectins reacted with the polar cap and recognized several bands
      (from 20 to 160 kDa) on blots of E. cuniculi protein extracts. Physicochemical
      analyses provided the first determination of major glycostructures in
      microsporidia. O-linked glycans were demonstrated to be linear manno
      oligosaccharides containing up to eight alpha1, 2-linked mannose residues, thus
      resembling those reported in some fungi such as Candida albicans. No N-linked
      glycans were detected. The data are in accordance with gene-based prediction of a
      minimal O-mannosylation pathway. Further identification of individual
      mannoproteins should help in the understanding of spore germination mechanism and
      host-microsporidia interactions.

PMID- 16980328
TI  - Dysbindin-1 is a synaptic and microtubular protein that binds brain snapin.
AB  - Variations in the gene encoding the novel protein dysbindin-1 (DTNBP1) are among
      the most commonly reported genetic variations associated with schizophrenia.
      Recent studies show that those variations are also associated with cognitive
      functioning in carriers with and without psychiatric diagnoses, suggesting a
      general role for dysbindin-1 in cognition. Such a role could stem from the
      protein's known ability to affect neuronal glutamate release. How dysbindin-1
      might affect glutamate release nevertheless remains unknown without the discovery
      of the protein's neuronal binding partners and its subcellular locus of action.
      We demonstrate here that snapin is a binding partner of dysbindin-1 in vitro and
      in the brain. Tissue fractionation of whole mouse brains and human hippocampal
      formations revealed that both dysbindin-1 and snapin are concentrated in tissue
      enriched in synaptic vesicle membranes and less commonly in postsynaptic
      densities. It is not detected in presynaptic tissue fractions lacking synaptic
      vesicles. Consistent with that finding, immunoelectron microscopy showed that
      dysbindin-1 is located in (i) synaptic vesicles of axospinous terminals in the
      dentate gyrus inner molecular layer and CA1 stratum radiatum and in (ii)
      postsynaptic densities and microtubules of dentate hilus neurons and CA1
      pyramidal cells. The labeled synapses are often asymmetric with thick
      postsynaptic densities suggestive of glutamatergic synapses, which are likely to
      be derived from dentate mossy cells and CA3 pyramidal cells. The function of
      dysbindin-1 in presynaptic, postsynaptic and microtubule locations may all be
      related to known functions of snapin.

PMID- 16980329
TI  - A primate-specific acceleration in the evolution of the caspase-dependent
      apoptosis pathway.
AB  - Programmed cell death, or apoptosis, plays an essential role in mammalian
      development, especially the development of the nervous system. Here, we
      systematically examine the molecular evolution of the mammalian intrinsic
      apoptosis program. We divided the program into its several constituent pathways
      and examined the evolution of each pathway in diverse mammalian taxa spanning
      primates, rodents and carnivores. We observed that genes involved in the caspase
      dependent apoptosis pathway stood out in several ways. First, these genes display
      an accelerated rate of protein sequence evolution in primates relative to rodents
      or carnivores. Secondly, this acceleration is most pronounced along the lineage
      leading to humans, and it is associated with signatures of positive selection.
      Finally, several genes in this pathway, including APAF1, CASP9 and CASP3, have
      been shown to be associated with dramatic defects in neuronal cell number and
      brain size when mutated in mice. These observations suggest the possibility that
      evolutionary changes in the caspase-dependent apoptosis pathway may have
      contributed to brain evolution in primates and humans. Our results also lend
      further support to the hypothesis that genes regulating brain size during
      development might have played a particularly important role in transforming brain
      size during evolution.

PMID- 16980330
TI  - Legislating fear and the public health in gilded age Massachusetts.
AB  - Between 1876 and 1881 Massachusetts experienced an outbreak of human rabies
      (hydrophobia). The entire state--the Governor, the legislature, the State Board
      of Health, newspapers, and the citizenry and elected officials of every town and
      city--reacted to the disease. Central to the response was the Commonwealth's
      legislature--called the General Court. Through public hearings, their own
      debates, and the passage of legislation, it resolved widespread fear and anger,
      mediated conflicting concepts of disease, and promoted social solidarity in the
      face of an epidemic. This article first narrates the General Court's legislative
      actions; it then examines the conflicting understandings of disease causality;
      finally, it explores the social and political rituals the legislature drew upon
      to deal with this public health crisis. Arguing that public health legislation is
      simultaneously instrumental and symbolic, this article demonstrates that
      attention to both enriches the study of epidemics, historical and yet to come.

PMID- 16980331
TI  - The U.S. Public Health Service and smoking in the 1950s: the tale of two more
      statements.
AB  - During the 1950s, the United States Public Health Service prepared two statements
      on the link between smoking and lung cancer that have not been recognized by
      other historians. This article employs extended discussions of these two
      statements as vehicles to explore both internal developments at the federal
      health agency and larger questions surrounding the disciplinary emergence of
      chronic disease epidemiology. The primary cast of characters includes Surgeons
      General Leonard A. Scheele and Leroy E. Burney, Lewis C. Robbins (a lower-ranking
      Public Health Service officer, who had chief responsibility for the agency's
      smoking-related programs from 1958 through 1962 and who left behind a daily
      professional diary), and Journal of the American Medical Association (JAMA)
      editor John H. Talbott. These men, and others, are seen grappling (at varying
      levels of engagement) with the appearance of what we now recognize as a
      profoundly different way of understanding chronic disease causation, which
      centers on survey-taking and statistical analysis of risk factors.

PMID- 16980332
TI  - Outcomes in off-pump vs. on-pump coronary artery bypass grafting stratified by
      pre-operative risk profile: an assessment using propensity score.
AB  - AIMS: To assess the benefit of off-pump coronary surgery stratified by the pre
      operative risk profile. METHODS AND RESULTS: Prospective and multicentric cohort
      study. All consecutive patients undergoing a first coronary bypass procedure
      between November 2001 and November 2003 were potentially eligible. Pre-operative
      EuroSCORE and in-hospital outcomes were prospectively collected using strictly
      standardized criteria. To ensure optimal adjustment, a propensity score was
      constructed using clinically relevant variables and incorporating individual
      centres. Of 1602 patients who underwent a first coronary bypass, EuroSCORE could
      be calculated in 1585: 787 were of moderate/high pre-operative risk profile
      (EuroSCORE > 3), of which 347 underwent off-pump procedures, and 798 were of low
      pre-operative risk profile (EuroSCORE < or = 3), of which 349 underwent off-pump
      procedures. After risk adjusting for propensity score, off-pump patients had less
      major events (post-operative death, myocardial infarction, and need for
      reoperation). This benefit was higher in the low-risk stratum (OR ranged between
      0.27 and 0.4; P = 0.02-0.07) than in the high-risk stratum (OR between 0.4 and
      0.7; P, not significant). CONCLUSION: In real-life conditions, off-pump coronary
      surgery may be more effective than on-pump surgery. In contrast with previous
      reports, our results suggest that this benefit may be higher in patients with low
      pre-operative risk.

PMID- 16980333
TI  - Autoimmune limbic encephalitis in 39 patients: immunophenotypes and outcomes.
AB  - BACKGROUND: About 40% of patients with limbic encephalitis do not have detectable
      CNS antibodies. Some of these patients have immune-mediated limbic encephalitis,
      but their frequency is unknown. AIMS: (1) To determine the spectrum of limbic
      encephalitis identified on clinical grounds in a single institution, and compare
      it with that in patients referred for antibody analysis. (2) To correlate
      clinical outcomes with the cellular location of the autoantigens. METHODS:
      Prospective clinical case studies. Immunohistochemistry with rat brain, live
      hippocampal neurones, HeLa cells expressing Kv potassium channels and immunoblot.
      RESULTS: In 4 years, 17 patients were identified in the Hospital of the
      University of Pennsylvania, Philadelphia, USA, and the serum or CSF samples of 22
      patients diagnosed elsewhere were also studied. 9 of our 17 (53%) patients had
      antibodies to known neuronal antigens (paraneoplastic or voltage gated potassium
      channels (VGKCs)) and 5 (29%) to novel cell-membrane antigens (nCMAg) typically
      expressed in the hippocampus and sometimes in the cerebellum. Considering the
      entire series, 19 of 39 (49%) patients had antibodies to known antigens, and 17
      (44%) to nCMAg. Follow-up (2-48 months, median 19 months) was available for 35
      patients. When compared with patients with antibodies to intraneuronal antigens,
      a significant association with response to treatment was found in those with
      antibodies to cell-membrane antigens in general (VGKC or nCMAg, p = 0.003) or to
      nCMAg (p = 0.006). CONCLUSIONS: (1) 82% of patients with limbic encephalitis
      prospectively identified on clinical grounds had CNS antibodies; (2)
      responsiveness to treatment is not limited to patients with VGKC antibodies; (3)
      in many patients (29% from a single institution), the autoantigens were unknown
      but were found to be highly enriched in neuronal cell membranes of the
      hippocampus; and (4) these antibodies are associated with a favourable outcome.

PMID- 16980334
TI  - Training-induced cortical representation of a hemianopic hemifield.
AB  - BACKGROUND: Patients with homonymous hemianopia often have some residual
      sensitivity for visual stimuli in their blind hemifield. Previous imaging studies
      suggest an important role for extrastriate cortical areas in such residual
      vision, but results of training to improve vision in patients with hemianopia are
      conflicting. OBJECTIVE: To show that intensive training with flicker stimulation
      in the chronic stage of stroke can reorganise visual cortices of an adult
      patient. METHODS: A 61-year-old patient with homonymous hemianopia was trained
      with flicker stimulation, starting 22 months after stroke. Changes in functioning
      during training were documented with magnetoencephalography, and the cortical
      organisation after training was examined with functional magnetic resonance
      imaging (fMRI). RESULTS: Both imaging methods showed that, after training, visual
      information from both hemifields was processed mainly in the intact hemisphere.
      The fMRI mapping results showed the representations of both the blind and the
      normal hemifield in the same set of cortical areas in the intact hemisphere, more
      specifically in the visual motion-sensitive area V5, in a region around the
      superior temporal sulcus and in retinotopic visual areas V1 (primary visual
      cortex), V2, V3 and V3a. CONCLUSIONS: Intensive training of a blind hemifield can
      induce cortical reorganisation in an adult patient, and this case shows an
      ipsilateral representation of the trained visual hemifield in several cortical
      areas, including the primary visual cortex.

PMID- 16980335
TI  - IL1RN intron 2 polymorphism caused by variable number tandem repeats is
      associated with 1-year outcome in patients with ischaemic stroke.
AB  - BACKGROUND: Results of experimental and clinical studies suggest that recombinant
      human interleukin 1 receptor antagonist (rhIL1ra) may be a good new therapeutic
      agent for acute stroke. In humans, IL1ra is encoded by the IL1RN gene located on
      chromosome 2. OBJECTIVES: To report on the association between different
      genotypes of the variable number tandem repeat (VNTR) polymorphism within IL1RN,
      and disease severity and 1-year outcome in patients with ischaemic stroke.
      METHODS: IL1RN genotypes were evaluated using polymerase chain reaction in 391
      patients with ischaemic stroke diagnosed according to the World Health
      Organization definition. The effects of IL1RN genotypes on severity of stroke at
      maximum impairment, and on the survival status and neurological and functional
      condition of patients at 7 days, 1 month, 3 months and 1 year after the onset,
      were evaluated. RESULTS: No relationship was found between IL1RN genotypes and
      severity of symptoms at the time of maximum impairment. Homozygotes for the
      IL1RN*2 allele showed less severe neurological and functional impairments when
      assessed after the time period between 7 days and 1 year after stroke compared
      with carriers of the other two IL1RN genotypes. Patients with at least one copy
      of the IL1RN*2 allele had increased risk of death during the first week, and
      patients homozygotic for this allele had increased risk of death within the first
      month after stroke. CONCLUSION: IL1RN intron 2 variable number tandem repeats
      polymorphism influences the clinical outcome in patients with ischaemic stroke.
      It may possibly modify effects of treatment with rhIL1ra in patients with acute
      stroke.

PMID- 16980336
TI  - The effect of the apolipoprotein E gene polymorphisms and haplotypes on
      behavioural and psychological symptoms in probable Alzheimer's disease.
AB  - BACKGROUND: Patients with Alzheimer's disease and dementia commonly suffer from
      behavioural and psychological symptoms of dementia (BPSD). A genetic component to
      BPSD development in Alzheimer's disease has been demonstrated. Several studies
      have investigated whether the exon 4 epsilon2/epsilon3/epsilon4 haplotype of the
      apolipoprotein E (APOE) gene is associated with BPSD, with variable results.
      OBJECTIVE: We investigated the exon 4 polymorphisms and extended this study to
      include promoter polymorphisms and the resultant haplotypes across the gene.
      METHODS: Our large independent cohort of 388 patients with longitudinal measures
      of BPSD assessed by the Neuropsychiatric Inventory was used to analyse whether
      any of these variants were associated with the presence of BPSD. RESULTS: We
      revealed several significant relationships before correction for multiple
      testing. The exon 4 haplotype was associated with hallucinations and anxiety, A
      491T with irritability, T-427C with agitation/aggression and appetite
      disturbances, and T-219C with depression. Haplotype analyses of all variants did
      not reveal any statistically significant findings. CONCLUSIONS: Our data and a
      review of previous studies showed a diversity of relationships, suggesting that
      these findings might be due to chance and so collectively do not support a role
      for the APOE gene in BPSD.

PMID- 16980337
TI  - In silico assessment of Y1795C and Y1795H SCN5A mutations: implication for
      inherited arrhythmogenic syndromes.
AB  - The effects of two SCN5A mutations (Y1795C, Y1795H), previously identified in one
      Long QT syndrome type 3 (LQT3) and one Brugada syndrome (BrS) families, were
      investigated by means of numerical modeling of ventricular action potential (AP).
      A Markov model capable of reproducing a wild-type as well as a mutant sodium
      current (I(Na)) was identified and was included into the Luo-Rudy ventricular
      cell model for action potential (AP) simulation. The characteristics of
      endocardial, midmyocardial, and epicardial cells were reproduced by
      differentiating the transient outward current (I(TO)) and the ratio of slow
      delayed rectifier potassium (I(Ks)) to rapid delayed rectifier current (I(Kr)).
      Administration of flecainide and mexiletine was simulated by appropriately
      modifying I(Na), calcium current (I(Ca)), I(TO), and I(Kr). Y1795C prolonged AP
      in a rate-dependent manner, and early afterdepolarizations (EADs) appeared during
      bradycardia in epicardial and midmyocardial cells; flecainide and mexiletine
      shortened AP and abolished EADs. Y1795H resulted in minimal changes in the APs;
      flecainide but not mexiletine induced APs heterogeneity across the ventricular
      wall that accounts for the ST segment elevation induced by flecainide in Y1795H
      carriers. The AP abnormalities induced by Y1795H and Y1795C can explain the
      clinically observed surface ECG phenotype. For the first time by modeling the
      effects of flecainide and mexiletine, we are able to gather mechanistic insights
      on the response to drugs administration observed in affected patients.

PMID- 16980338
TI  - Intratracheal mesenchymal stem cell administration attenuates monocrotaline
      induced pulmonary hypertension and endothelial dysfunction.
AB  - The administration of mesenchymal stem cells (MSCs) has been proposed for the
      treatment of pulmonary hypertension. However, the effect of intratracheally
      administered MSCs on the pulmonary vascular bed in monocrotaline-treated rats has
      not been determined. In the present study, the effect of intratracheal
      administration of rat MSCs (rMSCs) on monocrotaline-induced pulmonary
      hypertension and impaired endothelium-dependent responses were investigated in
      the rat. Intravenous injection of monocrotaline increased pulmonary arterial
      pressure and vascular resistance and decreased pulmonary vascular responses to
      acetylcholine without altering responses to sodium nitroprusside and without
      altering systemic responses to the vasodilator agents when responses were
      evaluated at 5 wk. The intratracheal injection of 3 x 10(6) rMSCs 2 wk after
      administration of monocrotaline attenuated the rise in pulmonary arterial
      pressure and pulmonary vascular resistance and restored pulmonary responses to
      acetylcholine toward values measured in control rats. Treatment with rMSCs
      decreased the right ventricular hypertrophy induced by monocrotaline.
      Immunohistochemical studies showed widespread distribution of lacZ-labeled rMSCs
      in lung parenchyma surrounding airways in monocrotaline-treated rats.
      Immunofluorescence studies revealed that transplanted rMSCs retained expression
      of von Willebrand factor and smooth muscle actin markers specific for endothelial
      and smooth muscle phenotypes. However, immunolabeled cells were not detected in
      the wall of pulmonary vessels. These data suggest that the decrease in pulmonary
      vascular resistance and improvement in response to acetylcholine an endothelium
      dependent vasodilator in monocrotaline-treated rats may result from a paracrine
      effect of the transplanted rMSCs in lung parenchyma, which improves vascular
      endothelial function in the monocrotaline-injured lung.

PMID- 16980339
TI  - C2C12 skeletal muscle cells adopt cardiac-like sodium current properties in a
      cardiac cell environment.
AB  - Intracardiac transplantation of undifferentiated skeletal muscle cells
      (myoblasts) has emerged as a promising therapy for myocardial infarct repair and
      is already undergoing clinical trials. The fact that cells originating from
      skeletal muscle have different electrophysiological properties than
      cardiomyocytes, however, may considerably limit the success of this therapy and,
      in addition, cause side effects. Indeed, a major problem observed after myoblast
      transplantation is the occurrence of ventricular arrhythmias. The most often
      transient nature of these arrhythmias may suggest that, once transplanted into
      cardiac tissue, skeletal muscle cells adopt more cardiac-like
      electrophysiological properties. To test whether a cardiac cell environment can
      indeed modify electrophysiological parameters of skeletal muscle cells, we
      treated mouse C(2)C(12) myocytes with medium preconditioned by primary
      cardiocytes and compared their functional sodium current properties with those of
      control cells. We found this treatment to significantly alter the activation and
      inactivation properties of sodium currents from "skeletal muscle" to more
      "cardiac"-like ones. Sodium currents of cardiac-conditioned cells showed a
      reduced sensitivity to block by tetrodotoxin. These findings and reverse
      transcription PCR experiments suggest that an upregulation of the expression of
      the cardiac sodium channel isoform Na(v)1.5 versus the skeletal muscle isoform
      Na(v)1.4 is responsible for the observed changes in sodium current function. We
      conclude that cardiomyocytes alter sodium channel isoform expression of skeletal
      muscle cells via a paracrine mechanism. Thereby, skeletal muscle cells with more
      cardiac-like sodium current properties are generated.

PMID- 16980340
TI  - Gadolinium does not blunt the cardiovascular responses at the onset of voluntary
      static exercise in cats: a predominant role of central command.
AB  - The cardiovascular adaptation at the onset of voluntary static exercise is
      controlled by the autonomic nervous system. Two neural mechanisms are responsible
      for the cardiovascular adaptation: one is central command descending from higher
      brain centers, and the other is a muscle mechanosensitive reflex from activation
      of mechanoreceptors in the contracting muscles. To examine which mechanism played
      a major role in producing the initial cardiovascular adaptation during static
      exercise, we studied the effect of intravenous administration of gadolinium (55
      micromol/kg), a blocker of stretch-activated ion channels, on the increases in
      heart rate (HR) and mean arterial blood pressure (MAP) at the onset of voluntary
      static exercise (pressing a bar with a forelimb) in conscious cats. HR increased
      by 31 +/- 5 beats/min and MAP increased by 15 +/- 1 mmHg at the onset of
      voluntary static exercise. Gadolinium affected neither the baseline values nor
      the initial increases of HR and MAP at the onset of exercise, although the peak
      force applied to the bar tended to decrease to 65% of the control value before
      gadolinium. Furthermore, we examined the effect of gadolinium on the reflex
      responses in HR and MAP (18 +/- 7 beats/min and 30 +/- 6 mmHg, respectively)
      during passive mechanical stretch of a forelimb or hindlimb in anesthetized cats.
      Gadolinium significantly blunted the passive stretch-induced increases in HR and
      MAP, suggesting that gadolinium blocks the stretch-activated ion channels and
      thereby attenuates the reflex cardiovascular responses to passive mechanical
      stretch of a limb. We conclude that the initial cardiovascular adaptation at the
      onset of voluntary static exercise is predominantly induced by feedforward
      control of central command descending from higher brain centers but not by a
      muscle mechanoreflex.

PMID- 16980341
TI  - Interactions of VEGF isoforms with VEGFR-1, VEGFR-2, and neuropilin in vivo: a
      computational model of human skeletal muscle.
AB  - The vascular endothelial growth factor (VEGF) family of cytokines is involved in
      the maintenance of existing adult blood vessels as well as in angiogenesis, the
      sprouting of new vessels. To study the proangiogenic activation of VEGF receptors
      (VEGFRs) by VEGF family members in skeletal muscle, we develop a computational
      model of VEGF isoforms (VEGF(121), VEGF(165)), their cell surface receptors, and
      the extracellular matrix in in vivo tissue. We build upon our validated model of
      the biochemical interactions between VEGF isoforms and receptor tyrosine kinases
      (VEGFR-1 and VEGFR-2) and nonsignaling neuropilin-1 coreceptors in vitro. The
      model is general and could be applied to any tissue; here we apply the model to
      simulate the transport of VEGF isoforms in human vastus lateralis muscle, which
      is extensively studied in physiological experiments. The simulations predict the
      distribution of VEGF isoforms in resting (nonexercising) muscle and the
      activation of VEGFR signaling. Little of the VEGF protein in muscle is present as
      free, unbound extracellular cytokine; the majority is bound to the cell surface
      receptors or to the extracellular matrix. However, interstitial sequestration of
      VEGF(165) does not affect steady-state receptor binding. In the absence of
      neuropilin, VEGF(121) and VEGF(165) behave similarly, but neuropilin enhances the
      binding of VEGF(165) to VEGFR-2. This model is the first to study VEGF tissue
      distribution and receptor activation in human muscle, and it provides a platform
      for the design and evaluation of therapeutic approaches.

PMID- 16980342
TI  - Lack of osteopontin improves cardiac function in streptozotocin-induced diabetic
      mice.
AB  - The purpose of this study was to investigate the role of osteopontin (OPN) in
      diabetic hearts. Diabetes was induced in wild-type (WT) and OPN knockout (KO)
      mice by using streptozotocin (150 mg/kg) injection. Left ventricular (LV)
      structural and functional remodeling was studied 30 and 60 days after induction
      of diabetes. Induction of diabetes increased OPN expression in cardiac myocytes.
      Heart weight-to-body weight ratio was increased in both diabetic (D) groups. Lung
      wet weight-to-dry weight ratio was increased only in the WT-D group. Peak left
      ventricular (LV) developed pressures measured using Langendorff perfusion
      analyses were reduced to a greater extent in WT-D versus KO-D group. LV end
      diastolic pressure-volume curve exhibited a significant leftward shift in WT-D
      but not in KO-D group. LV end-diastolic diameter, percent fractional shortening,
      and the ratio of peak velocity of early and late filling (E/A wave) were
      significantly reduced in WT-D mice as analyzed by echocardiography. The increase
      in cardiac myocyte apoptosis and fibrosis was significantly higher in the WT-D
      group. Expression of atrial natriuretic peptide and transforming growth factor
      beta1 was significantly increased in the WT-D group. Induction of diabetes
      increased protein kinase C (PKC) phosphorylation in both groups. However,
      phosphorylation of PKC-betaII was significantly higher in the WT-D group, whereas
      phosphorylation of PKC-zeta was significantly higher in the KO-D group. Levels of
      peroxisome proliferator-activated receptor-gamma were significantly decreased in
      the WT-D group but not in the KO-D group. Thus increased expression of OPN may
      play a deleterious role during streptozotocin-induced diabetic cardiomyopathy
      with effects on cardiac fibrosis, hypertrophy, and myocyte apoptosis.

PMID- 16980343
TI  - Aging associated with mild dyslipidemia reveals that COX-2 preserves dilation
      despite endothelial dysfunction.
AB  - The endothelial function declines with age, and dyslipidemia (DL) has been shown
      to hasten this process by favoring the generation of reactive oxygen species
      (ROS). Cyclooxygenase-2 (COX-2) can be induced by ROS, but its contribution to
      the regulation of the endothelial function is unknown. Since COX-2 inhibitors may
      be deleterious to the cardiovascular system, we hypothesized that DL leads to ROS
      dependent endothelial damage and a protective upregulation of COX-2. Dilations to
      acetylcholine (ACh) of renal arteries isolated from 3-, 6-, and 12-mo-old wild
      type (WT) and DL mice expressing the human ApoB-100 were recorded with or without
      COX inhibitors and the antioxidant N-acetyl-l-cystein (NAC). Nitric oxide (NO)
      and endothelium-derived hyperpolarizing factor (EDHF) were inhibited using
      N(omega)-nitro-l-arginine (l-NNA) and a depolarizing solution, respectively. In
      WT mice, the dilation to ACh declined at 12 mo but was insensitive to COX-1/2
      inhibition alone or with NAC. DL led to an early endothelial dysfunction at 6 mo,
      normalized, however, by NAC. At 12 mo, vascular sensitivity to ACh was further
      reduced by DL. At this age, selective COX-2 inhibition reduced the dilation,
      whereas addition of NAC improved it. In 3- and 6-mo-old WT mice, l-NNA
      significantly reduced the dilation, whereas it limited the dilation only in 3-mo
      old DL mice. EDHF-dependent dilation remains identical in both groups. These data
      suggest that COX-2 activity confers endothelium-dependent vasodilatory function
      in aged DL mice in the face of a pro-oxidative environment. Upregulation of this
      pathway compensates for the early loss of the contribution of NO in DL mice.

PMID- 16980344
TI  - Induction of matrix metalloproteinase-2 enhances systemic arterial contraction
      after hypoxia.
AB  - This study was carried out to determine the role of increased vascular matrix
      metalloproteinase-2 (MMP-2) expression in the changes in systemic arterial
      contraction after prolonged hypoxia. Rats and mice were exposed to hypoxia (10%
      and 8% O(2), respectively) or normoxia (21% O(2)) for 16 h, 48 h, or 7 days.
      Aortae and mesenteric arteries were either mounted in organ bath myographs or
      frozen in liquid nitrogen. MMP-2 inhibition with cyclic CTTHWGFTLC (CTT) reduced
      contraction to phenylephrine (PE) in aortae and mesenteric arteries from rats
      exposed to hypoxia for 7 days but not in vessels from normoxic rats. Similarly,
      CTT reduced contraction to Big endothelin-1 (Big ET-1) in aortae from rats
      exposed to hypoxia for 7 days. Responses to PE were reduced in hypoxic MMP-2(-/-)
      mice compared with MMP-2(+/+) mice. Increased contraction to Big ET-1 after
      hypoxia was observed in MMP-2(+/+) mice but not in MMP-2(-/-) mice. Rat aortic
      MMP-2 and membrane type 1 (MT1)-MMP protein levels and MMP activity were
      increased after 7 days of hypoxia. Rat aortic MMP-2 and MT1-MMP mRNA levels were
      increased in the deep medial vascular smooth muscle. We conclude that hypoxic
      induction of MMP-2 expression potentiates contraction in systemic conduit and
      resistance arteries. This may preserve the capacity to regulate the systemic
      circulation in the transition between the alterations in vascular tone and
      structural remodeling that occurs during prolonged hypoxic epochs.

PMID- 16980345
TI  - Role of Cav1.2 L-type Ca2+ channels in vascular tone: effects of nifedipine and
      Mg2+.
AB  - Ca(2+) entry via L-type voltage-gated Ca(2+) channels (LVGCs) is a key factor in
      generating myogenic tone (MT), as dihydropyridines (DHPs) and other LVGC
      blockers, including Mg(2+), markedly reduce MT. Recent reports suggest, however,
      that elevated external Mg(2+) concentration and DHPs may also inhibit other
      Ca(2+)-entry pathways. Here, we explore the contribution of LVGCs to MT in
      intact, pressurized mesenteric small arteries using mutant mice (DHP(R/R))
      expressing functional but DHP-insensitive Ca(v)1.2 channels. In wild-type (WT),
      but not DHP(R/R), mouse arteries, nifedipine (0.3-1.0 microM) markedly reduced MT
      and vasoconstriction induced by high external K(+) concentrations ([K(+)](o)), a
      measure of LVGC-mediated Ca(2+) entry. Blocking MT and high [K(+)](o)-induced
      vasoconstriction by <1 microM nifedipine in WT but not in DHP(R/R) arteries
      implies that Ca(2+) entry via Ca(v)1.2 LVGCs is obligatory for MT and that
      nifedipine inhibits MT exclusively by blocking LVGCs. We also examined the
      effects of Mg(2+) on MT and LVGCs. High external Mg(2+) concentration (10 mM)
      blocked MT, slowed the high [K(+)](o)-induced vasoconstrictions, and decreased
      their amplitude in WT and DHP(R/R) arteries. To verify that these effects of
      Mg(2+) are due to block of LVGCs, we characterized the effects of extracellular
      and intracellular Mg(2+) on LVGC currents in isolated mesenteric artery myocytes.
      DHP-sensitive LVGC currents are inhibited by both external and internal Mg(2+).
      The results indicate that Mg(2+) relaxes MT by inhibiting Ca(2+) influx through
      LVGCs. These data provide new information about the central role of Ca(v)1.2
      LVGCs in generating and maintaining MT in mouse mesenteric small arteries.

PMID- 16980346
TI  - ANG II-induced hypertension and the role of the area postrema during normal and
      increased dietary salt.
AB  - It has been shown that the area postrema (AP) plays a role in the development of
      certain types of chronic angiotensin II (ANG II)-induced hypertension in the rat
      but is not of great importance in the salt sensitivity of arterial pressure. It
      has recently been proposed, however, that elevated sodium levels may exacerbate
      the hypertensive effects of ANG II, which by itself dramatically affects salt
      sensitivity, by acting at sodium-sensing neurons in certain circumventricular
      organs of the brain. Thus the interactions of ANG II, sodium, and the central
      nervous system remain to be fully understood. The purpose of this study was to
      examine the role of the AP in ANG II-induced hypertension during periods of
      normal and elevated dietary salt. We hypothesized that an intact AP was necessary
      for the full development of hypertension under chronic ANG II infusion and that
      its role would be pronounced during periods of increased dietary sodium. To test
      this, male Sprague-Dawley rats underwent ablation of the area postrema (APx, n =
      6) or sham operation (sham, n = 6). After 3 wk of recovery, rats were
      instrumented with radiotelemetry transducers for constant blood pressure and
      heart rate monitoring and venous catheters for vehicle infusion. After a 3-day
      control period of 0.9% saline infusion (7 ml/day) and 0.4% dietary sodium, a 10
      day period of ANG II infusion (10 ng.kg(-1).min(-1)) was begun, immediately
      followed by a second 10-day period during which rats were fed a 4.0% sodium diet.
      By day 6 of ANG II infusion, mean arterial pressure (MAP) in APx rats had
      increased to 139 +/- 4 mmHg, whereas MAP in sham rats had increased to 126 +/- 3
      mmHg. This difference was found to be significant and continued through day 1 of
      the high-salt period, after which MAP of the two groups had risen to similar
      levels. On day 9 of high salt, MAP was again observed to be significantly higher
      (162 +/- 1 mmHg) in APx rats when compared with sham rats (147 +/- 4 mmHg.) These
      results do not support the hypothesis that the AP is necessary for the full
      development of ANG II-induced hypertension at normal or elevated levels of
      dietary sodium.

PMID- 16980347
TI  - Transforming growth factor-beta1 decreases cardiac muscle L-type Ca2+ current and
      charge movement by acting on the Cav1.2 mRNA.
AB  - Transforming growth factors-beta (TGF-betas) are essential to the structural
      remodeling seen in cardiac disease and development; however, little is known
      about potential electrophysiological effects. We hypothesized that chronic
      exposure (6-48 h) of primary cultured neonatal rat cardiomyocytes to the type 1
      TGF-beta (TGF-beta1, 5 ng/ml) may affect voltage-dependent Ca(2+) channels. Thus
      we investigated T- (I(CaT)) and L-type (I(CaL)) Ca(2+) currents, as well as
      dihydropyridine-sensitive charge movement using the whole cell patch-clamp
      technique and quantified Ca(V)1.2 mRNA levels by real-time PCR assay. In
      ventricular myocytes, TGF-beta1 did not exert significant electrophysiological
      effects. However, in atrial myocytes, TGF-beta1 reduced both I(CaL) and charge
      movement (55% at 24-48 h) without significantly altering I(CaT), cell membrane
      capacitance, or channel kinetics (voltage dependence of activation and
      inactivation, as well as the activation and inactivation rates). Reductions of
      I(CaL) and charge movement were explained by concomitant effects on the maximal
      values of L-channels conductance (G(max)) and charge movement (Q(max)). Thus TGF
      beta1 selectively reduces the number of functional L-channels on the surface of
      the plasma membrane in atrial but not ventricular myocytes. The TGF-beta1-induced
      I(CaL) reduction was unaffected by supplementing intracellular recording
      solutions with okadaic acid (2 microM) or cAMP (100 microM), two compounds that
      promote L-channel phosphorylation. This suggests that the decreased number of
      functional L-channels cannot be explained by a possible regulation in the L
      channels phosphorylation state. Instead, we found that TGF-beta1 decreases the
      expression levels of atrial Ca(V)1.2 mRNA (70%). Thus TGF-beta1 downregulates
      atrial L-channel expression and may be therefore contributing to the in vivo
      cardiac electrical remodeling.

PMID- 16980348
TI  - P-selectin-mediated adhesion impairs endothelium-dependent arteriolar dilation in
      hypercholesterolemic mice.
AB  - Hypercholesterolemia is associated with an attenuation of endothelium-dependent
      dilation in arterioles and an increase in leukocyte and platelet adhesion in
      venules. The proximity of closely paired arterioles and venules is thought to
      facilitate heat and mass transport between the two and could be involved in
      transport of inflammatory and/or vasoactive mediators from venule to arteriole.
      In the current study, we tested the hypothesis that the impaired arteriolar
      dilation associated with hypercholesterolemia might be dependent on P-selectin
      dependent blood cell adhesion in the closely paired venules. Leukocyte and
      platelet recruitment in venules and the endothelium-dependent response to
      bradykinin in second-order arterioles were observed in the mouse intestinal
      submucosa using intravital microscopy. Four weeks of a high-cholesterol diet
      decreased bradykinin-induced arteriolar dilation more dramatically in closely
      paired arterioles than in distantly paired arterioles. The dysfunctional
      arteriolar dilation of closely paired arterioles in hypercholesterolemic mice was
      significantly improved when the experiments were repeated in P-selectin-deficient
      mice (given the high-cholesterol diet) or in hypercholesterolemic mice injected
      with a P-selectin monoclonal antibody. A similar improvement in dilation of
      closely paired arterioles was attained in hypercholesterolemic mice given the
      superoxide dismutase mimetic Tempol. These findings indicate that
      hypercholesterolemia-induced increases in venular leukocyte and platelet adhesion
      might contribute to the impaired endothelium-dependent dilation of closely paired
      arterioles via a mechanism that is distance limited and dependent on P-selectin
      and superoxide.

PMID- 16980349
TI  - Effects of residential exercise training on heart rate recovery in coronary
      artery patients.
AB  - The aims of the present study are twofold: 1) to investigate whether heart rate
      recovery (HRR) after a cycle ergometry test is affected by exercise training and
      2) to test the ability of HRR to replicate the baroreflex sensitivity (BRS)
      changes that occur in response to an exercise training program in coronary artery
      patients. We randomized 82 coronary artery patients undergoing a residential
      cardiac rehabilitation program to an exercise training group (TR; n = 43) and an
      untrained group (UTR; n = 39). All of the patients underwent an exercise test
      before and after the rehabilitation program. HRR was recorded at the end of the
      1st and 2nd min after exercise. BRS was determined at rest before and after
      treatment. HRR after the 2nd min was significantly improved in TR patients (-21.4
      +/- 0.9 beats/min) compared with UTR patients (-17.8 +/- 1.2 beats/min) at the
      end of the training program. Improvement in HRR paralleled that in BRS in TR
      patients (from 3.2 +/- 0.3 to 5.3 +/- 0.8 ms/mmHg; P < 0.001), whereas no
      significant change was evident in UTR patients (from 3.5 +/- 0 to 4.0 +/- 0.4
      ms/mmHg; P = 0.230). Our data show that HRR in the 2nd min after the cessation of
      a cycle ergometer exercise test increased in coronary artery patients after an
      exercise training period. This result confirms the positive effect induced by
      exercise training on HRR and extends the conclusions of previous studies to
      different modalities of exercise (i.e., cycle ergometer). HRR might provide an
      additional simple marker of the effectiveness of physical training programs in
      cardiac patients.

PMID- 16980350
TI  - The A2a/A2b receptor antagonist ZM-241385 blocks the cardioprotective effect of
      adenosine agonist pretreatment in in vivo rat myocardium.
AB  - There is increasing evidence for interactions among adenosine receptor subtypes
      in the brain and heart. The purpose of this study was to determine whether the
      adenosine A(2a) receptor modulates the infarct size-reducing effect of
      preischemic administration of adenosine receptor agonists in intact rat
      myocardium. Adult male rats were submitted to in vivo regional myocardial
      ischemia (25 min) and 2 h reperfusion. Vehicle-treated rats were compared with
      rats pretreated with the A(1) agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA,
      10 mug/kg), the nonselective agonist 5'-N-ethylcarboxamidoadenosine (NECA, 10
      mug/kg), or the A(2a) agonist 2-[4-(2-carboxyethyl)phenethylamino]-5'-N
      methylcarboxamidoadenosine (CGS-21680, 20 mug/kg). Additional CCPA- and NECA
      treated rats were pretreated with the A(1) antagonist 8-cyclopentyl-1,3
      dipropylxanthine (DPCPX, 100 mug/kg), the A(2a)/A(2b) antagonist 4-(-2-[7-amino-2
      {2-furyl}{1,2,4}triazolo{2,3-a} {1,3,5}triazin-5-yl-amino]ethyl)phenol (ZM
      241385, 1.5 mg/kg) or the A(3) antagonist 3-propyl-6-ethyl-5[(ethylthio)carbonyl]
      2-phenyl-4-propyl-3-pyridine carboxylate (MRS-1523, 2 mg/kg). CCPA and NECA
      reduced myocardial infarct size by 50% and 35%, respectively, versus vehicle, but
      CGS-21680 had no effect. DPCPX blunted the bradycardia associated with CCPA and
      NECA, whereas ZM-241385 attenuated their hypotensive effects. Both DPCPX and ZM
      241385 blocked the protective effects of CCPA and NECA. The A(3) antagonist did
      not alter the hemodynamic effects of CCPA or NECA, nor did it alter adenosine
      agonist cardioprotection. None of the antagonists alone altered myocardial
      infarct size. These findings suggest that although preischemic administration of
      an A(2a) receptor agonist does not induce cardioprotection, antagonism of the
      A(2a) and/or the A(2b) receptor blocks the cardioprotection associated with
      adenosine agonist pretreatment.

PMID- 16980351
TI  - Biology of bone marrow-derived endothelial cell precursors.
AB  - Over the past decade, the old idea that the bone marrow contains endothelial cell
      precursors has become an area of renewed interest. While some still believe that
      there are no endothelial precursors in the blood, even among those who do, there
      is no consensus as to what they are or what they do. In this review, we describe
      the problems in identifying endothelial cells and conclude that expression of
      endothelial nitric oxide synthase may be the most reliable antigenic indicator of
      the phenotype. The evidence for two different classes of endothelial precursors
      is also presented. We suggest that, though there is no single endothelial cell
      precursor, we may be able to use these phenotypic variations to our advantage in
      better understanding their biology. We also discuss how a variety of genetic,
      epigenetic, and methodological differences can account for the seemingly
      contradictory findings on the physiological relevance of bone marrow-derived
      precursors in normal vascular maintenance and in response to injury. Data on the
      impact of tumor type and location on the contribution of bone marrow-derived
      cells to the tumor vasculature are also presented. These data provide hope that
      we may ultimately be able to predict those tumors in which bone marrow-derived
      cells will have a significant contribution and design therapies accordingly.
      Finally, factors that regulate bone marrow cell recruitment to and function in
      the endothelium are beginning to be identified, and several of these, including
      stromal derived factor 1, monocyte chemoattractant factor-1, and vascular
      endothelial growth factor are discussed.

PMID- 16980352
TI  - Toll-like receptor 2 modulates left ventricular function following ischemia
      reperfusion injury.
AB  - Production of proinflammatory cytokines contributes to cardiac dysfunction during
      ischemia-reperfusion. The principal mechanism responsible for the induction of
      this innate stress response during periods of myocardial ischemia-reperfusion
      remains unknown. Toll-like receptor 2 (TLR2) is a highly conserved pattern
      recognition receptor that has been implicated in the innate immune response to a
      variety of pathogens. However, TLR2 may also mediate inflammation in response to
      noninfectious injury. We therefore hypothesized that TLR2 is essential for
      modulating myocardial inflammation and left ventricular (LV) function during
      ischemia-reperfusion injury. Susceptibility to myocardial ischemia-reperfusion
      injury following ischemia-reperfusion was determined in Langendorff-perfused
      hearts isolated from wild-type mice and mice deficient in TLR2 (TLR2D) and Toll
      interleukin receptor domain-containing adaptor protein. After ischemia
      reperfusion, contractile performance was significantly impaired in hearts from
      wild-type mice as demonstrated by a lower recovery of LV developed pressure
      relative to TLR2D hearts. Creatinine kinase levels were similar in both groups
      after reperfusion. Contractile dysfunction in wild-type hearts was associated
      with elevated cardiac levels of TNF and IL-1beta. Ischemia-reperfusion-induced LV
      dysfunction was reversed by treatment with the recombinant TNF blocking protein
      etanercept. These studies show for the first time that TLR2 signaling importantly
      contributes to the LV dysfunction that occurs following ischemia-reperfusion.
      Thus disruption of TLR2-mediated signaling may be helpful to induce immediate or
      delayed myocardial protection from ischemia-reperfusion injury.

PMID- 16980353
TI  - Attributes of glycosylation in the establishment of the unfolding pathway of
      soybean agglutinin.
AB  - Soybean agglutinin (gSBA) is a tetrameric legume lectin, each of whose subunits
      are glycosylated. Earlier studies have shown that this protein shows
      exceptionally high stability in terms of free energy of unfolding when compared
      to other proteins from the same family. This article deals with the unfolding
      reactions of the nonglycosylated recombinant form of the protein rSBA and its
      comparison with the glycosylated counterpart gSBA. The nonglycosylated form
      features a lower stability when compared to the glycosylated form. Further, the
      unfolding pathways in the two are widely different. Although the glycosylated
      form undergoes a simple two-state unfolding, the nonglycosylated species unfolds
      via a compact monomeric intermediate that is not a molten globule. Representative
      isothermal and thermal denaturation profiles show that glycosylation accounts for
      a stabilization of approximately 9 kcal/mol of the tetramer, whereas the
      difference in T(m) between the two forms is 26 degrees C. Computational studies
      on the glycan-protein interactions at the noncanonical interface of the protein
      show that quite a number of hydrogen bond and hydrophobic interactions stabilize
      the glycoprotein tetramer.

PMID- 16980354
TI  - Alcohols reduce lateral membrane pressures: predictions from molecular theory.
AB  - We explore the effects of alcohols on fluid lipid bilayers using a molecular
      theory with a coarse-grained model. We show that the trends predicted from the
      theory in the changes in area per lipid, alcohol concentration in the bilayer,
      and area compressibility modulus, as a function of alcohol chain length and of
      the alcohol concentration in the solvent far from the bilayer, follow those found
      experimentally. We then use the theory to study the effect of added alcohol on
      the lateral pressure profile across the membrane, and find that added alcohol
      reduces the surface tensions at both the headgroup/solvent and
      headgroup/tailgroup interfaces, as well as the lateral pressures in the headgroup
      and tailgroup regions. These changes in lateral pressures could affect the
      conformations of membrane proteins, providing a nonspecific mechanism for the
      biological effects of alcohols on cells.

PMID- 16980355
TI  - K+ conduction in the selectivity filter of potassium channels is monitored by the
      charge distribution along their sequence.
AB  - Potassium channels display a high conservation of sequence of the selectivity
      filter (SF), yet nature has designed a variety of channels that present a wide
      range of absolute rates of K(+) permeation. In KcsA, the structural archetype for
      K channels, under physiological concentrations, two K(+) ions reside in the SF in
      configurations 1,3 (up state) and 2,4 (down state) and ion conduction is believed
      to follow a throughput cycle involving a transition between these states. Using
      free-energy calculations of KcsA, Kv1.2, and mutant channels, we show that this
      transition is characterized by a channel-dependent energy barrier. This barrier
      is strongly influenced by the charges partitioned along the sequence of each
      channel. These results unveil therefore how, for similar structures of the SF,
      the rate of K(+) turnover may be fine-tuned within the family of potassium
      channels.

PMID- 16980356
TI  - Modeling, docking, and simulation of the major facilitator superfamily.
AB  - X-ray structures are known for three members of the Major Facilitator Superfamily
      (MFS) of membrane transporter proteins, thus enabling the use of homology
      modeling to extrapolate to other MFS members. However, before employing such
      models for, e.g., mutational or docking studies, it is essential to develop a
      measure of their quality. To aid development of such metrics, two disparate MFS
      members (NupG and GLUT1) have been modeled. In addition, control models were
      created with shuffled sequences, to mimic poor quality homology models. These
      models and the template crystal structures have been examined in terms of both
      static and dynamic indicators of structural quality. Comparison of the behavior
      of modeled structures with the crystal structures in molecular dynamics
      simulations provided a metric for model quality. Docking of the inhibitor
      forskolin to GLUT1 and to a control model revealed significant differences,
      indicating that we may identify accurate models despite low sequence identity
      between target sequences and templates.

PMID- 16980358
TI  - Dual-color photon counting histogram analysis of mRFP1 and EGFP in living cells.
AB  - We investigate the potential of dual-color photon counting histogram (PCH)
      analysis to resolve fluorescent protein mixtures directly inside cells. Because
      of their small spectral overlap, we have chosen to look at the fluorescent
      proteins EGFP and mRFP1. We experimentally demonstrate that dual-color PCH
      quantitatively resolves a mixture of EGFP and mRFP1 in cells from a single
      measurement. To mimic the effect of protein association, we constructed a fusion
      protein of EGFP and mRFP1 (denoted EGFP-mRFP1). Fluorescence resonant energy
      transfer within the fusion protein alters the dual-channel brightness of the
      fluorophores. We describe a model for fluorescence resonant energy transfer
      effects on the brightness and incorporate it into dual-color PCH analysis. The
      model is verified using fluorescence lifetime measurements. Dual-color PCH
      analysis demonstrated that not all of the expressed EGFP-mRFP1 fusion proteins
      contained a fluorescent mRFP1 molecule. Fluorescence lifetime and emission
      spectra measurements confirmed this surprising result. Additional experiments
      show that the missing fluorescent fraction of mRFP1 is consistent with a dark
      state population of mRFP1. We successfully resolved this mixture of fusion
      proteins with a single dual-color PCH measurement. These results highlight the
      potential of dual-color PCH to directly detect and quantify protein mixtures in
      living cells.

PMID- 16980357
TI  - Resurrecting abandoned proteins with pure water: CD and NMR studies of protein
      fragments solubilized in salt-free water.
AB  - Many proteins expressed in Escherichia coli cells form inclusion bodies that are
      neither refoldable nor soluble in buffers. Very surprisingly, we recently
      discovered that all 11 buffer-insoluble protein fragments/domains we have, with a
      great diversity of cellular function, location, and molecular size, could be
      easily solubilized in salt-free water. The circular dichroism (CD) and NMR
      characterization led to classification of these proteins into three groups: group
      1, with no secondary structure by CD and with narrowly-dispersed but sharp (1)H
      (15)N heteronuclear single quantum correlation (HSQC) peaks; group 2, with
      secondary structure by CD but with HSQC peaks broadened and, consequently, only a
      small set of peaks detectable; and group 3, with secondary structure by CD and
      also well-separated HSQC peaks. Intriguingly, we failed to find any protein with
      a tight tertiary packing. Therefore, we propose that buffer-insoluble proteins
      may lack intrinsic ability to reach or/and to maintain a well-packed
      conformation, and thus are trapped in partially-folded states with many
      hydrophobic side chains exposed to the bulk solvent. As such, a very low ionic
      strength is sufficient to screen out intrinsic repulsive interactions and,
      consequently, allow the hydrophobic clustering/aggregation to occur. Marvelously
      enough, it appears that in pure water, proteins have the potential to manifest
      their full spectrum of structural states by utilizing intrinsic repulsive
      interactions to suppress the attractive hydrophobic clustering. Our discovery not
      only gives a novel insight into the properties of insoluble proteins, but also
      sheds the first light that we know of on previously unknown regimes associated
      with proteins.

PMID- 16980359
TI  - Temperature-dependence of isometric tension and cross-bridge kinetics of cardiac
      muscle fibers reconstituted with a tropomyosin internal deletion mutant.
AB  - The effect of temperature on isometric tension and cross-bridge kinetics was
      studied with a tropomyosin (Tm) internal deletion mutant AS-Delta23Tm (Ala-Ser-Tm
      Delta(47-123)) in bovine cardiac muscle fibers by using the thin filament
      extraction and reconstitution technique. The results are compared with those from
      actin reconstituted alone, cardiac muscle-derived control acetyl-Tm, and
      recombinant control AS-Tm. In all four reconstituted muscle groups, isometric
      tension and stiffness increased linearly with temperature in the range 5-40
      degrees C for fibers activated in the presence of saturating ATP and Ca(2+). The
      slopes of the temperature-tension plots of the two controls were very similar,
      whereas the slope derived from fibers with actin alone had approximately 40% the
      control value, and the slope from mutant Tm had approximately 36% the control
      value. Sinusoidal analysis was performed to study the temperature dependence of
      cross-bridge kinetics. All three exponential processes A, B, and C were
      identified in the high temperature range (30-40 degrees C); only processes B and
      C were identified in the mid-temperature range (15-25 degrees C), and only
      process C was identified in the low temperature range (5-10 degrees C). At a
      given temperature, similar apparent rate constants (2pia, 2pib, 2pic) were
      observed in all four muscle groups, whereas their magnitudes were markedly less
      in the order of AS-Delta23Tm < Actin < AS-Tm approximately Acetyl-Tm groups. Our
      observations are consistent with the hypothesis that Tm enhances hydrophobic and
      stereospecific interactions (positive allosteric effect) between actin and
      myosin, but Delta23Tm decreases these interactions (negative allosteric effect).
      Our observations further indicate that tension/cross-bridge is increased by Tm,
      but is diminished by Delta23Tm. We conclude that Tm affects the conformation of
      actin so as to increase the area of hydrophobic interaction between actin and
      myosin molecules.

PMID- 16980360
TI  - Dynamic studies of scaffold-dependent mating pathway in yeast.
AB  - The mating pathway in Saccharomyces cerevisiae is one of the best understood
      signal transduction pathways in eukaryotes. It transmits the mating signal from
      plasma membrane into the nucleus through the G-protein coupled receptor and the
      mitogen-activated protein kinase (MAPK) cascade. According to current
      understanding of the mating pathway, we construct a system of ordinary
      differential equations to describe the process. Our model is consistent with a
      wide range of experiments, indicating that it captures some main characteristics
      of the signal transduction along the pathway. Investigation with the model
      reveals that the shuttling of the scaffold protein and the dephosphorylation of
      kinases involved in the MAPK cascade cooperate to regulate the response upon
      pheromone induction and to help preserve the fidelity of the mating signaling. We
      explored factors affecting the dose-response curves of this pathway and found
      that both negative feedback and concentrations of the proteins involved in the
      MAPK cascade play crucial roles. Contrary to some other MAPK systems where
      signaling sensitivity is being amplified successively along the cascade, here the
      mating signal is transmitted through the cascade in an almost linear fashion.

PMID- 16980361
TI  - Beneath the minerals, a layer of round lipid particles was identified to mediate
      collagen calcification in compact bone formation.
AB  - Astronauts lose 1-2% of their bone minerals per month during space flights. A
      systematic search for a countermeasure relies on a good understanding of the
      mechanism of bone formation at the molecular level. How collagen fibers, the
      dominant matrix protein in bones, are mineralized remains mysterious. Atomic
      force microscopy was carried out, in combination with immunostaining and Western
      blotting, on bovine tibia to identify unrecognized building blocks involved in
      bone formation and for an elucidation of the process of collagen calcification in
      bone formation. Before demineralization, tiles of hydroxyapatite crystals were
      found stacked along bundles of collagen fibers. These tiles were homogeneous in
      size and shape with dimensions 0.69 x 0.77 x 0.2 micro m(3). Demineralization
      dissolved these tiles and revealed small spheres with an apparent diameter around
      145 nm. These spheres appeared to be lipid particles since organic solvents
      dissolved them. The parallel collagen bundles had widths mostly <2 micro m.
      Composition analysis of compact bones indicated a high content of apolar lipids,
      including triglycerides and cholesterol esters. Apolar lipids are known to form
      lipid droplets or lipoproteins, and these spheres are unlikely to be matrix
      vesicles as reported for collagen calcification in epiphyseal cartilages. Results
      from this study suggest that the layer of round lipid particles on collagen
      fibers mediates the mineral deposition onto the fibers. The homogeneous size of
      these lipid particles and the presence of apolipoprotein in demineralized bone
      tissue suggest the possibility that these particles might be of lipoprotein
      origin. More studies are needed to verify the last claim and to exclude the
      possibility that they are secreted lipid droplets.

PMID- 16980362
TI  - Infrared absorption study of the heme pocket dynamics of carbonmonoxyheme
      proteins.
AB  - The temperature dependencies of the infrared absorption CO bands of carboxy
      complexes of horseradish peroxidase (HRP(CO)) in glycerol/water mixture at pH 6.0
      and 9.3 are interpreted using the theory of optical absorption bandshape. The
      bands' anharmonic behavior is explained assuming that there is a higher-energy
      set of conformational substates (CSS(h)), which are populated upon heating and
      correspond to the protein substates with disordered water molecules in the heme
      pocket. Analysis of the second moments of the CO bands of the carboxy complexes
      of myoglobin (Mb(CO)) and hemoglobin (Hb(CO)), and of HRP(CO) with
      benzohydroxamic acid (HRP(CO)+BHA), shows that the low energy CSS(h) exists also
      in the open conformation of Mb(CO), where the heme pocket is spacious enough to
      accommodate a water molecule. In the HRP(CO)+BHA and closed conformations of
      Mb(CO) and Hb(CO), the heme pocket is packed with BHA and different amino acids,
      the CSS(h) has much higher energy and is hardly populated even at the highest
      temperatures. Therefore only motions of these amino acids contribute to the band
      broadening. These motions are linked to the protein surface and frozen in the
      glassy matrix, whereas in the liquid solvent they are harmonic. Thus the second
      moment of the CO band is temperature-independent in glass and is proportional to
      the temperature in liquid. The temperature dependence of the second moment of the
      CO peak of HRP(CO) in the trehalose glass exhibits linear coupling to an
      oscillator. This oscillator can be a moving water molecule locked in the heme
      pocket in the whole interval of temperatures or a trehalose molecule located in
      the heme pocket.

PMID- 16980363
TI  - 'Trigger' events precede calcium puffs in Xenopus oocytes.
AB  - The liberation of calcium ions sequestered in the endoplasmic reticulum through
      inositol 1,4,5-trisphosphate receptors/channels (IP(3)Rs) results in a
      spatiotemporal hierarchy of calcium signaling events that range from single
      channel openings to local Ca(2+) puffs believed to arise from several to tens of
      clustered IP(3)Rs to global calcium waves. Using high-resolution confocal
      linescan imaging and a sensitive Ca(2+) indicator dye (fluo-4-dextran), we show
      that puffs are often preceded by small, transient Ca(2+) elevations that we
      christen "trigger events". The magnitude of triggers is consistent with their
      arising from the opening of a single IP(3) receptor/channel, and we propose that
      they initiate puffs by recruiting neighboring IP(3)Rs within the cluster by a
      regenerative process of Ca(2+)-induced Ca(2+) release. Puff amplitudes
      (fluorescence ratio change) are on average approximately 6 times greater than
      that of the triggers, suggesting that at least six IP(3)Rs may simultaneously be
      open during a puff. Trigger events have average durations of approximately 12 ms,
      as compared to 19 ms for the mean rise time of puffs, and their spatial extent is
      approximately 3 times smaller than puffs (respective widths at half peak
      amplitude 0.6 and 1.6 micro m). All these parameters were relatively independent
      of IP(3) concentration, although the proportion of puffs showing resolved
      triggers was greatest (approximately 80%) at low [IP(3)]. Because Ca(2+) puffs
      constitute the building blocks from which cellular IP(3)-mediated Ca(2+) signals
      are constructed, the events that initiate them are likely to be of fundamental
      importance for cell signaling. Moreover, the trigger events provide a useful
      yardstick by which to derive information regarding the number and spatial
      arrangement of IP(3)Rs within clusters.

PMID- 16980364
TI  - The fundamental organization of cardiac mitochondria as a network of coupled
      oscillators.
AB  - Mitochondria can behave as individual oscillators whose dynamics may obey
      collective, network properties. We have shown that cardiomyocytes exhibit high
      amplitude, self-sustained, and synchronous oscillations of bioenergetic
      parameters when the mitochondrial network is stressed to a critical state.
      Computational studies suggested that additional low-amplitude, high-frequency
      oscillations were also possible. Herein, employing power spectral analysis, we
      show that the temporal behavior of mitochondrial membrane potential (DeltaPsi(m))
      in cardiomyocytes under physiological conditions is oscillatory and characterized
      by a broad frequency distribution that obeys a homogeneous power law (1/f(beta))
      with a spectral exponent, beta = 1.74. Additionally, relative dispersional
      analysis shows that mitochondrial oscillatory dynamics exhibits long-term memory,
      characterized by an inverse power law that scales with a fractal dimension (D(f))
      of 1.008, distinct from random behavior (D(f) = 1.5), over at least three orders
      of magnitude. Analysis of a computational model of the mitochondrial oscillator
      suggests that the mechanistic origin of the power law behavior is based on the
      inverse dependence of amplitude versus frequency of oscillation related to the
      balance between reactive oxygen species production and scavenging. The results
      demonstrate that cardiac mitochondria behave as a network of coupled oscillators
      under both physiological and pathophysiological conditions.

PMID- 16980365
TI  - Structural changes of cross-bridges on transition from isometric to shortening
      state in frog skeletal muscle.
AB  - Structural changes in the myosin cross-bridges were studied by small-angle x-ray
      diffraction at a time resolution of 0.53 ms. A frog sartorius muscle, which was
      electrically stimulated to induce isometric contraction, was released by
      approximately 1% in 1 ms, and then its length was decreased to allow steady
      shortening with tension of approximately 30% of the isometric level. Intensity of
      all reflections reached a constant level in 5-8 ms. Intensity of the 7.2-nm
      meridional reflection and the (1,0) sampling spot of the 14.5-nm layer line
      increased after the initial release but returned to the isometric level during
      steady shortening. The 21.5-nm meridional reflection showed fast and slow
      components of intensity increase. The intensity of the 10.3-nm layer line, which
      arises from myosin heads attached to actin, decreased to a steady level in 2 ms,
      whereas other reflections took longer, 5-20 ms. The results show that myosin
      heads adapt quickly to an altered level of tension, and that there is a distinct
      structural state just after a quick release.

PMID- 16980366
TI  - Chromophore-protein interactions in the anthozoan green fluorescent protein
      asFP499.
AB  - Despite their similar fold topologies, anthozoan fluorescent proteins (FPs) can
      exhibit widely different optical properties, arising either from chemical
      modification of the chromophore itself or from specific interactions of the
      chromophore with the surrounding protein moiety. Here we present a structural and
      spectroscopic investigation of the green FP asFP499 from the sea anemone Anemonia
      sulcata var. rufescens to explore the effects of the protein environment on the
      chromophore. The optical absorption and fluorescence spectra reveal two discrete
      species populated in significant proportions over a wide pH range. Moreover,
      multiple protonation reactions are evident from the observed pH-dependent
      spectral changes. The x-ray structure of asFP499, determined by molecular
      replacement at a resolution of 1.85 A, shows the typical beta-barrel fold of the
      green FP from Aequorea victoria (avGFP). In its center, the chromophore, formed
      from the tripeptide Gln(63)-Tyr(64)-Gly(65), is tightly held by multiple hydrogen
      bonds in a polar cage that is structurally quite dissimilar to that of avGFP. The
      x-ray structure provides interesting clues as to how the spectroscopic properties
      are fine tuned by the chromophore environment.

PMID- 16980367
TI  - Dynamics and stability of E-cadherin dimers.
AB  - The extracellular domains of cadherins are known to play a major role in cell
      adhesion, although the structures involved in this process remain unclear. We
      have used molecular dynamics to characterize the conformational and thermodynamic
      properties of two of the dimer interfaces identified in E-cadherin crystals and
      involving the two outermost exodomains (EC1 and EC2): a dimer involving exchange
      of the N-terminal strand (referred to as the "swapped" dimer) and a "staggered"
      dimer involving an EC1-EC2 interface. The results show that the staggered dimer
      involves a much smaller interface area and is notably less stable than the
      swapped dimer. It is also found that, despite its stability, the swapped dimer
      undergoes a conformational transition leading to a structure closer to that
      experimentally observed for the homologous C-cadherin. Finally, comparing the
      simulated dimer structures with the sequences of E-, C-, and N-cadherins shows
      that the swapped dimer interface involves surprisingly few residues that vary
      from family to family and notably no changes between the E- and C-cadherin
      exodomains.

PMID- 16980368
TI  - Ultra-high resolution imaging by fluorescence photoactivation localization
      microscopy.
AB  - Biological structures span many orders of magnitude in size, but far-field
      visible light microscopy suffers from limited resolution. A new method for
      fluorescence imaging has been developed that can obtain spatial distributions of
      large numbers of fluorescent molecules on length scales shorter than the
      classical diffraction limit. Fluorescence photoactivation localization microscopy
      (FPALM) analyzes thousands of single fluorophores per acquisition, localizing
      small numbers of them at a time, at low excitation intensity. To control the
      number of visible fluorophores in the field of view and ensure that optically
      active molecules are separated by much more than the width of the point spread
      function, photoactivatable fluorescent molecules are used, in this case the
      photoactivatable green fluorescent protein (PA-GFP). For these photoactivatable
      molecules, the activation rate is controlled by the activation illumination
      intensity; nonfluorescent inactive molecules are activated by a high-frequency
      (405-nm) laser and are then fluorescent when excited at a lower frequency. The
      fluorescence is imaged by a CCD camera, and then the molecules are either
      reversibly inactivated or irreversibly photobleached to remove them from the
      field of view. The rate of photobleaching is controlled by the intensity of the
      laser used to excite the fluorescence, in this case an Ar+ ion laser. Because
      only a small number of molecules are visible at a given time, their positions can
      be determined precisely; with only approximately 100 detected photons per
      molecule, the localization precision can be as much as 10-fold better than the
      resolution, depending on background levels. Heterogeneities on length scales of
      the order of tens of nanometers are observed by FPALM of PA-GFP on glass. FPALM
      images are compared with images of the same molecules by widefield fluorescence.
      FPALM images of PA-GFP on a terraced sapphire crystal surface were compared with
      atomic force microscopy and show that the full width at half-maximum of features
      approximately 86 +/- 4 nm is significantly better than the expected diffraction
      limited optical resolution. The number of fluorescent molecules and their
      brightness distribution have also been determined using FPALM. This new method
      suggests a means to address a significant number of biological questions that had
      previously been limited by microscope resolution.

PMID- 16980370
TI  - Robust reconstruction of the rate constant distribution using the phase function
      method.
AB  - Many biological processes exhibit complex kinetic behavior that involves a
      nontrivial distribution of rate constants. Characterization of the rate constant
      distribution is often critical for mechanistic understandings of these processes.
      However, it is difficult to extract a rate constant distribution from data
      measured in the time domain. This is due to the numerical instability of the
      inverse Laplace transform, a long-standing mathematical challenge that has
      hampered data analysis in many disciplines. Here, we present a method that allows
      us to reconstruct the probability distribution of rate constants from decay data
      in the time domain, without fitting to specific trial functions or requiring any
      prior knowledge of the rate distribution. The robustness (numerical stability) of
      this reconstruction method is numerically illustrated by analyzing data with
      realistic noise and theoretically proved by the continuity of the transformations
      connecting the relevant function spaces. This development enhances our ability to
      characterize kinetics and dynamics of biological processes. We expect this method
      to be useful in a broad range of disciplines considering the prevalence of
      complex exponential decays in many experimental systems.

PMID- 16980369
TI  - Differential detection of phospholipid fluidity, order, and spacing by
      fluorescence spectroscopy of bis-pyrene, prodan, nystatin, and merocyanine 540.
AB  - The properties of liquid-ordered, solid-ordered, and liquid-disordered phases
      were investigated by steady-state fluorescence spectroscopy in liposomes composed
      of mixtures of dipalmitoylphosphatidylcholine and cholesterol (0-40 mol %) as a
      function of temperature (24-51 degrees C). The fluorescent probes used (bis
      pyrene, nystatin, prodan, and merocyanine) were chosen because they differ in the
      location they occupy in the membrane and in the types of properties they sense.
      Comparison of phase diagrams with contour plots of the fluorescence data
      suggested that bis-pyrene is sensitive primarily to lipid order. In contrast,
      nystatin fluorescence intensity responded to changes in lipid fluidity. The shape
      of the prodan emission spectrum detected both liquid-solid and order-disorder
      transitions in the phase diagram. Merocyanine's behavior was more complex. First,
      it was more sensitive than any of the other probes to the membrane pretransition
      that occurs in the absence of cholesterol. Second, regardless of whether emission
      intensity, anisotropy, or spectral shape was observed, the probe appeared to
      distinguish two types of liquid-ordered phases, one with tightly packed lipids
      and one in which the apparent spacing among lipids was increased. The prodan data
      supported these results by displaying modest versions of these two observations.
      Together, the results identify eight regions within the phase diagram of
      distinguishable combinations of these physical properties. As an example of how
      this combined analysis can be applied to biological membranes, human erythrocytes
      were treated similarly. Temperature variation at constant cholesterol content
      revealed three of the eight combinations identified in our analysis of liposomes.

PMID- 16980371
TI  - Dihedral-angle information entropy as a gauge of secondary structure propensity.
AB  - Protein structural information can be uncovered using an information-theory-based
      entropy and auxiliary functions by taking advantage of high-quality correlation
      plots between the dihedral angles around a residue and those between sequential
      residues. A standard information entropy for a primary sequence has been defined
      using the values of the probabilities of the most likely dihedral angles along
      the sequence. The distribution of entropy differences relative to the standard
      for each protein in a reference set--a sublibrary of the Protein Data Bank at the
      90% sequence redundancy level--appears to be nearly Gaussian. It gives rise to an
      auxiliary checking function whose value signals the extent to which the dihedral
      angle propensities differ from typical structures. Such deviations can arise
      either because of incorrect dihedral angle assignments or secondary structural
      propensities that are atypical of the structures in the reference set. This
      auxiliary checking function can be readily calculated at the public website,
      (http://www.d2check.gatech.edu). Its utility is demonstrated here in an analysis
      displaying differences between experimentally and theoretically derived
      structures, and in the analysis of structures derived by homology modeling. A
      comparison of the new measure, D(2)Check, to other checking functions based on
      backbone conformation-namely, PROCHECK and WHAT_CHECK--is also provided.

PMID- 16980372
TI  - The number and spatial distribution of IP3 receptors underlying calcium puffs in
      Xenopus oocytes.
AB  - Calcium puffs are local Ca(2+) release events that arise from a cluster of
      inositol 1,4,5-trisphosphate receptor channels (IP(3)Rs) and serve as a basic
      "building block" from which global Ca(2+) waves are generated. Important
      questions remain as to the number of IP(3)Rs that open during a puff, their
      spatial distribution within a cluster, and how much Ca(2+) current flows through
      each channel. The recent discovery of "trigger" events-small Ca(2+) signals that
      immediately precede puffs and are interpreted to arise through opening of single
      IP(3)R channels-now provides a useful yardstick by which to calibrate the Ca(2+)
      flux underlying puffs. Here, we describe a deterministic numerical model to
      simulate puffs and trigger events. Based on confocal linescan imaging in Xenopus
      oocytes, we simulated Ca(2+) release in two sequential stages; representing the
      trigger by the opening of a single IP(3)R in the center of a cluster for 12 ms,
      followed by the concerted opening of some number of IP(3)Rs for 19 ms,
      representing the rising phase of the puff. The diffusion of Ca(2+) and Ca(2+)
      bound indicator dye were modeled in a three-dimensional cytosolic volume in the
      presence of immobile and mobile Ca(2+) buffers, and were used to predict the
      observed fluorescence signal after blurring by the microscope point-spread
      function. Optimal correspondence with experimental measurements of puff spatial
      width and puff/trigger amplitude ratio was obtained assuming that puffs arise
      from the synchronous opening of 25-35 IP(3)Rs, each carrying a Ca(2+) current of
      approximately 0.4 pA, with the channels distributed through a cluster 300-800 nm
      in diameter.

PMID- 16980373
TI  - The lung in the balance: arginine, methylated arginines, and nitric oxide.

PMID- 16980374
TI  - Regulation of airway smooth muscle alpha-actin expression by glucocorticoids.
AB  - Airway smooth muscle hypertrophy appears to be present in severe asthma. However,
      the effect of corticosteroids on airway smooth muscle cell size or contractile
      protein expression has not been studied. We examined the effects of
      dexamethasone, fluticasone, and salmeterol on contractile protein expression in
      transforming growth factor (TGF)-beta-treated primary bronchial smooth muscle
      cells. Dexamethasone and fluticasone, but not salmeterol, each reduced expression
      of alpha-smooth muscle actin and the short isoform of myosin light chain kinase.
      Steady-state alpha-actin mRNA level and stability were unchanged, consistent with
      posttranscriptional control. Fluticasone significantly decreased alpha-actin
      protein synthesis following treatment with the transcriptional inhibitor
      actinomycin D, indicative of an inhibitory effect on mRNA translation.
      Fluticasone also significantly increased alpha-actin protein turnover. Finally,
      fluticasone reduced TGF-beta-induced incorporation of alpha-actin into
      filamentous actin, cell length, and cell shortening in response to ACh and KCl.
      We conclude that glucocorticoids reduce human airway smooth muscle alpha-smooth
      muscle actin expression and incorporation into contractile filaments, as well as
      contractile function, in part by attenuation of mRNA translation and enhancement
      of protein degradation.

PMID- 16980375
TI  - Expression and activity of cAMP phosphodiesterase isoforms in pulmonary artery
      smooth muscle cells from patients with pulmonary hypertension: role for PDE1.
AB  - Pulmonary hypertension (PHT) is associated with increased vascular resistance due
      to sustained contraction and enhanced proliferation of pulmonary arterial smooth
      muscle cells (PASMC); the abnormal tone and remodeling in the pulmonary
      vasculature may relate, at least in part, to decreased cyclic nucleotide levels.
      Cyclic nucleotide phosphodiesterases (PDEs), of which 11 families have been
      identified, catalyze the hydrolysis of cAMP and cGMP. We tested the hypothesis
      that PASMC isolated from patients with PHT, either idiopathic pulmonary arterial
      hypertension (IPAH) or secondary pulmonary hypertension (SPH), have increased
      expression and activity of PDE isoforms that reduce the responsiveness of agents
      that raise cellular cAMP. Real-time PCR and immunoblotting demonstrated that the
      expression of PDE1A, PDE1C, PDE3B, and PDE5A was enhanced in PASMC from both IPAH
      and SPH patients compared with control PASMC. Consistent with this enhanced
      expression of PDEs, agonist-stimulated cAMP levels were significantly reduced in
      IPAH and SPH PASMC unless a PDE inhibitor was present. The use of specific PDE
      inhibitors revealed that an increase in PDE1 and PDE3 activity largely accounted
      for reduced agonist-induced cAMP levels and increased proliferation in IPAH and
      SPH PASMC. Treatment with PDE1C-targeted small interference RNA enhanced cAMP
      accumulation and inhibited cellular proliferation to a greater extent in PHT
      PASMC than controls. The results imply that an increase in PDE isoforms, in
      particular PDE1C, contributes to decreased cAMP and increased proliferation of
      PASMC in patients with PHT. PDE1 isoforms may provide novel targets for the
      treatment of both primary and secondary forms of the disease.

PMID- 16980376
TI  - Intrapleural activation, processing, efficacy, and duration of protection of
      single-chain urokinase in evolving tetracycline-induced pleural injury in
      rabbits.
AB  - Intrapleural fibrinolysins have been used to treat pleural loculations. However,
      the efficacy of clinically available agents has recently been questioned,
      providing a rationale for investigation of new interventions. Single-chain
      urokinase plasminogen activator resists inhibition by serpins, and repeated,
      daily intrapleural administration of this agent prevents intrapleural loculation
      more effectively than complexes of this proenzyme with its receptor (Idell S,
      Mazar A, Cines D, Kuo A, Parry G, Gawlak S, Juarez J, Koenig K, Azghani A, Hadden
      W, McLarty J, Miller E. Am J Respir Crit Care Med 166: 920-926, 2002).
      Understanding of the protective mechanism and intrapleural processing remains
      unclear. We speculated that single-chain urokinase could induce sustained local
      fibrinolysis and protection by selective administration either before, during, or
      following loculation after pleural injury induced by tetracycline in rabbits.
      Enzymography, immunoassays, histology, immunohistochemistry, morphology, and
      morphometry were used to test the efficacy, duration of protective effect, and
      processing of single-chain urokinase. Intrapleural single chain urokinase
      prevented loculation at 72 h after injury (P < 0.01) if given either before or
      during adhesion formation and was converted to two-chain high-molecular-weight
      urokinase, which remained active for at least 24 h within pleural fluids. The
      effect was dose dependent, and established loculations at 72 h after tetracycline
      induced injury were reversed at 96 h by single-dose treatment. Single-chain
      urokinase bound and saturated intrapleural plasminogen activator inhibitory (PAI)
      1-like activity and urokinase-related immunoreactivity of the mesothelium was
      comparable in treatment or vehicle-control groups. Adhesions recurred by 2 wk
      after treatment with recurrence of excess local PAI activity. Single-chain
      urokinase induces sustained local fibrinolysis and reversibly prevents pleural
      loculation for up to 48 h after intrapleural administration after tetracycline
      induced injury.

PMID- 16980377
TI  - Inactivation of neuregulin-1 by nitration.
AB  - Nitration is a posttranslational modification that can compromise protein
      function. We hypothesized that nitration of growth factors secreted in the lung
      may alter their interaction with their respective receptors and modulate the
      normal growth and differentiation program induced by ligand-receptor interaction.
      We tested this hypothesis in vitro by nitration of neuregulin-1's (NRG-1) EGF
      like domain and studying the effect on NRG-1's activity. Nitration of NRG-1's
      (nNRG-1) EGF-like domain resulted in an inability to activate its receptor, the
      human epidermal growth factor receptors 2 and 3 (HER2/HER3) heterodimer, as
      defined by loss of HER2 tyrosine phosphorylation induced by nNRG-1 in MCF-7
      cells. Receptor activation was not restored with increasing nNRG-1 concentration
      or exposure times. nNRG-1 did not compete with NRG-1 for HER2/HER3 binding in
      competition assays. In addition, nNRG-1 no longer induced proliferation of the
      MCF-7 cell line, as MCF-7 cells exposed to nNRG-1 and NRG-1 concurrently had the
      same proliferation rate as that induced by NRG-1 alone. Thus nitration of NRG-1's
      EGF-like domain caused it to lose its ability to bind and activate its receptor
      with loss of ligand-induced proliferation. Posttranslational nitration of growth
      factors in states where reactive nitrogen species are increased may be an
      important means of regulating growth factor receptor effects in the lung.

PMID- 16980378
TI  - Regulation of rat alveolar type 2 cell proliferation in vitro involves type II
      cAMP-dependent protein kinase.
AB  - To elucidate the role of cAMP and different cAMP-dependent protein kinases (PKA;
      A-kinase) in lung cell proliferation, we investigated rat alveolar type 2 cell
      proliferation in relation to activation or inhibition of PKA and PKA regulatory
      subunits (RIIalpha and RIalpha). Both the number of proliferating type 2 cells
      and the level of different regulatory subunits varied during 7 days of culture.
      The cells exhibited a distinct peak of proliferation after 5 days of culture.
      This proliferation peak was preceded by a rise in RIIalpha protein level. In
      contrast, an inverse relationship between RIalpha and type 2 cell proliferation
      was noted. Activation of PKA increased type 2 cell proliferation if given at peak
      RIIalpha expression. Furthermore, PKA inhibitors lowered the rate of
      proliferation only when a high RII level was observed. An antibody against the
      anchoring region of RIIalpha showed cell cycle-dependent binding in contrast to
      antibodies against other regions, possibly related to altered binding to A-kinase
      anchoring protein. Following activation of PKA, relocalization of RIIalpha was
      confirmed by immunocytochemistry. In conclusion, it appears that activation of
      PKA II is important in regulation of alveolar type 2 cell proliferation.

PMID- 16980379
TI  - TNF-alpha downregulates the leukotriene C4 synthase gene in mononuclear
      phagocytes.
AB  - We studied the effect of tumor necrosis factor (TNF)-alpha exposure on cysteinyl
      leukotriene (LT) synthesis by cells of monocyte/macrophage lineage. TNF-alpha
      conditioning of monocytic THP-1 cells and primary human monocytes resulted in a
      decreased capacity for LTC(4) release. TNF-alpha exposure (for 16-24 h) decreased
      LTC(4) synthase mRNA in THP-1 cells, primary mouse bone marrow-derived
      macrophages, and eosinophilic AML14.3D10 cells. TNF-alpha downregulated LTC(4)
      synthase mRNA in THP-1 cells in a dose- and time-dependent manner, with
      downregulation observed as early as 4 h. The effect of TNF-alpha on LTC(4)
      synthase mRNA expression was mediated via the MEK/ERK pathway, but not via
      cyclooxygenase or nitric oxide synthase pathways. Conditioning of actinomycin D
      treated cells with TNF-alpha did not accelerate degradation of LTC(4) synthase
      mRNA. TNF-alpha produced sustained activation of p50 and p65, which were
      previously reported by our group to decrease LTC(4) synthase promoter activity.
      In transiently transfected THP-1 cells, TNF-alpha decreased promoter activity via
      an element located within the first 620 bp of the promoter. We conclude that TNF
      alpha exposure downregulates the synthetic capacity for cysteinyl LT release and
      LTC(4) synthase gene expression in monocytes/macrophages via a transcriptional
      mechanism.

PMID- 16980380
TI  - Effect of ramipril on the incidence of diabetes.
AB  - BACKGROUND: Previous studies have suggested that blockade of the renin
      angiotensin system may prevent diabetes in people with cardiovascular disease or
      hypertension. METHODS: In a double-blind, randomized clinical trial with a 2-by-2
      factorial design, we randomly assigned 5269 participants without cardiovascular
      disease but with impaired fasting glucose levels (after an 8-hour fast) or
      impaired glucose tolerance to receive ramipril (up to 15 mg per day) or placebo
      (and rosiglitazone or placebo) and followed them for a median of 3 years. We
      studied the effects of ramipril on the development of diabetes or death,
      whichever came first (the primary outcome), and on secondary outcomes, including
      regression to normoglycemia. RESULTS: The incidence of the primary outcome did
      not differ significantly between the ramipril group (18.1%) and the placebo group
      (19.5%; hazard ratio for the ramipril group, 0.91; 95% confidence interval [CI],
      0.81 to 1.03; P=0.15). Participants receiving ramipril were more likely to have
      regression to normoglycemia than those receiving placebo (hazard ratio, 1.16; 95%
      CI, 1.07 to 1.27; P=0.001). At the end of the study, the median fasting plasma
      glucose level was not significantly lower in the ramipril group (102.7 mg per
      deciliter [5.70 mmol per liter]) than in the placebo group (103.4 mg per
      deciliter [5.74 mmol per liter], P=0.07), though plasma glucose levels 2 hours
      after an oral glucose load were significantly lower in the ramipril group (135.1
      mg per deciliter [7.50 mmol per liter] vs. 140.5 mg per deciliter [7.80 mmol per
      liter], P=0.01). CONCLUSIONS: Among persons with impaired fasting glucose levels
      or impaired glucose tolerance, the use of ramipril for 3 years does not
      significantly reduce the incidence of diabetes or death but does significantly
      increase regression to normoglycemia. (ClinicalTrials.gov number, NCT00095654
      [ClinicalTrials.gov].).

PMID- 16980381
TI  - Angiotensin-converting-enzyme inhibitors for impaired glucose tolerance--is there
      still hope?

PMID- 16980382
TI  - Genetic evidence for phospholipid-mediated regulation of the Rab GDP-dissociation
      inhibitor in fission yeast.
AB  - We have previously identified mutant alleles of genes encoding two Rab proteins,
      Ypt3 and Ryh1, through a genetic screen using the immunosuppressant drug FK506 in
      fission yeast. In the same screen, we isolated gdi1-i11, a mutant allele of the
      essential gdi1+ gene encoding Rab GDP-dissociation inhibitor. In gdi1-i11, a
      conserved Gly267 was substituted by Asp. The Gdi1G267D protein failed to extract
      Rabs from membrane and Rabs were depleted from the cytosolic fraction in the gdi1
      i11 mutant cells. Consistently, the Gdi1G267D protein was found mostly in the
      membrane fraction, whereas wild-type Gdi1 was found in both the cytosolic and the
      membrane fraction. Notably, overexpression of spo20+, encoding a
      phosphatidylcholine/phosphatidylinositol transfer protein, rescued gdi1-i11
      mutation, but not ypt3-i5 or ryh1-i6. The gdi1-i11 and spo20-KC104 mutations are
      synthetically lethal, and the wild-type Gdi1 failed to extract Rabs from the
      membrane in the spo20-KC104 mutant. The phosphatidylinositol-transfer activity of
      Spo20 is dispensable for the suppression of the gdi1-i11 mutation, suggesting
      that the phosphatidylcholine-transfer activity is important for the suppression.
      Furthermore, knockout of the pct1+ gene encoding a choline phosphate
      cytidyltransferase rescued the gdi1-i11 mutation. Together, our findings suggest
      that Spo20 modulates Gdi1 function via regulation of phospholipid metabolism of
      the membranes.

PMID- 16980383
TI  - Molecular assembly of meiotic proteins Asy1 and Zyp1 and pairing promiscuity in
      rye (Secale cereale L.) and its synaptic mutant sy10.
AB  - Assembly of two orthologous proteins associated with meiotic chromosome axes in
      Arabidopsis thaliana (Asy1 and Zyp1) was studied immunologically at meiotic
      prophase of meiosis of wild-type rye (Secale cereale) and its synaptic mutant
      sy10, using antibodies derived from A. thaliana. The temporal and spatial
      expression of the two proteins were similar in wild-type rye, but with one
      notable difference. Unlike A. thaliana, in which foci of the transverse filament
      protein Zyp1 appear to linearize commensurately with synapsis, linear tracts of
      Asy1 and Zyp1 protein form independently at leptotene and early zygotene of rye
      and coalign into triple structures resembling synaptonemal complexes (SCs) only
      at later stages of synapsis. The sy10 mutant used in this study also forms
      spatially separate linear tracts of Asy1 and Zyp1 proteins at leptotene and early
      zygotene, and these coalign but do not form regular triple structures at
      midprophase. Electron microscopy of spread axial elements reveals extensive
      asynapsis with some exchanges of pairing partners. Indiscriminate SCs support
      nonhomologous chiasma formation at metaphase I, as revealed by multi-color
      fluorescence in situ hybridization enabling reliable identification of all the
      chromosomes of the complement. Scrutiny of chiasmate associations of chromosomes
      at this stage revealed some specificity in the associations of homologous and
      nonhomologous chromosomes. Inferences about the nature of synapsis in this mutant
      were drawn from such observations.

PMID- 16980384
TI  - sli-3 negatively regulates the LET-23/epidermal growth factor receptor-mediated
      vulval induction pathway in Caenorhabditis elegans.
AB  - The LIN-3-LET-23-mediated inductive signaling pathway plays a major role during
      vulval development in C. elegans. Studies on the components of this pathway have
      revealed positive as well as negative regulators that function to modulate the
      strength and specificity of the signal transduction cascade. We have carried out
      genetic screens to identify new regulators of this pathway by screening for
      suppressors of lin-3 vulvaless phenotype. The screens recovered three loci
      including alleles of gap-1 and a new gene represented by sli-3. Our genetic
      epistasis experiments suggest that sli-3 functions either downstream or in
      parallel to nuclear factors lin-1 and sur-2. sli-3 synergistically interacts with
      the previously identified negative regulators of the let-23 signaling pathway and
      causes excessive cell proliferation. However, in the absence of any other
      mutation sli-3 mutant animals display wild-type vulval induction and morphology.
      We propose that sli-3 functions as a negative regulator of vulval induction and
      defines a branch of the inductive signaling pathway. We provide evidence that sli
      3 interacts with the EGF signaling pathway components during vulval induction but
      not during viability and ovulation processes. Thus, sli-3 helps define
      specificity of the EGF signaling to induce the vulva.

PMID- 16980385
TI  - The Caenorhabditis elegans rhy-1 gene inhibits HIF-1 hypoxia-inducible factor
      activity in a negative feedback loop that does not include vhl-1.
AB  - Hypoxia-inducible factor (HIF) transcription factors implement essential changes
      in gene expression that enable animals to adapt to low oxygen (hypoxia). The
      stability of the C. elegans HIF-1 protein is controlled by the evolutionarily
      conserved EGL-9/VHL-1 pathway for oxygen-dependent degradation. Here, we describe
      vhl-1-independent pathways that attenuate HIF-1 transcriptional activity in C.
      elegans. First, the expression of HIF-1 target genes is markedly higher in egl-9
      mutants than in vhl-1 mutants. We show that HIF-1 protein levels are similar in
      animals carrying strong loss-of-function mutations in either egl-9 or vhl-1. We
      conclude that EGL-9 inhibits HIF-1 activity, as well as HIF-1 stability. Second,
      we identify the rhy-1 gene and show that it acts in a novel negative feedback
      loop to inhibit expression of HIF-1 target genes. rhy-1 encodes a multi-pass
      transmembrane protein. Although loss-of-function mutations in rhy-1 cause
      relatively modest increases in hif-1 mRNA and HIF-1 protein expression, some HIF
      1 target genes are expressed at higher levels in rhy-1 mutants than in vhl-1
      mutants. Animals lacking both vhl-1 and rhy-1 function have a more severe
      phenotype than either single mutant. Collectively, these data support models in
      which RHY-1 and EGL-9 function in VHL-1-independent pathway(s) to repress HIF-1
      transcriptional activity.

PMID- 16980386
TI  - Linear element-independent meiotic recombination in Schizosaccharomyces pombe.
AB  - Most organisms form protein-rich, linear, ladder-like structures associated with
      chromosomes during early meiosis, the synaptonemal complex. In
      Schizosaccharomyces pombe, linear elements (LinEs) are thread-like, proteinacious
      chromosome-associated structures that form during early meiosis. LinEs are
      related to axial elements, the synaptonemal complex precursors of other
      organisms. Previous studies have led to the suggestion that axial structures are
      essential to mediate meiotic recombination. Rec10 protein is a major component of
      S. pombe LinEs and is required for their development. In this report we study
      recombination in a number of rec10 mutants, one of which (rec10-155) does not
      form LinEs, but is predicted to encode a truncated Rec10 protein. This mutant has
      levels of crossing over and gene conversion substantially higher than a rec10
      null mutant (rec10-175) and forms cytologically detectable Rad51 foci indicative
      of meiotic recombination intermediates. These data demonstrate that while Rec10
      is required for meiotic recombination, substantial meiotic recombination can
      occur in rec10 mutants that do not form LinEs, indicating that LinEs per se are
      not essential for all meiotic recombination.

PMID- 16980387
TI  - Differential requirement of DNA replication factors for subtelomeric ARS
      consensus sequence protosilencers in Saccharomyces cerevisiae.
AB  - The establishment of silent chromatin requires passage through S-phase, but not
      DNA replication per se. Nevertheless, many proteins that affect silencing are
      bona fide DNA replication factors. It is not clear if mutations in these
      replication factors affect silencing directly or indirectly via deregulation of S
      phase or DNA replication. Consequently, the relationship between DNA replication
      and silencing remains an issue of debate. Here we analyze the effect of mutations
      in DNA replication factors (mcm5-461, mcm5-1, orc2-1, orc5-1, cdc45-1, cdc6-1,
      and cdc7-1) on the silencing of a group of reporter constructs, which contain
      different combinations of "natural" subtelomeric elements. We show that the mcm5
      461, mcm5-1, and orc2-1 mutations affect silencing through subtelomeric ARS
      consensus sequences (ACS), while cdc6-1 affects silencing independently of ACS.
      orc5-1, cdc45-1, and cdc7-1 affect silencing through ACS, but also show ACS
      independent effects. We also demonstrate that isolated nontelomeric ACS do not
      recapitulate the same effects when inserted in the telomere. We propose a model
      that defines the modes of action of MCM5 and CDC6 in silencing.

PMID- 16980388
TI  - Drosophila model of human inherited triosephosphate isomerase deficiency
      glycolytic enzymopathy.
AB  - Heritable mutations, known as inborn errors of metabolism, cause numerous
      devastating human diseases, typically as a result of a deficiency in essential
      metabolic products or the accumulation of toxic intermediates. We have isolated a
      missense mutation in the Drosophila sugarkill (sgk) gene that causes phenotypes
      analogous to symptoms of triosephosphate isomerase (TPI) deficiency, a human
      familial disease, characterized by anaerobic metabolic dysfunction resulting from
      pathological missense mutations affecting the encoded TPI protein. In Drosophila,
      the sgk gene encodes the glycolytic enzyme TPI. Our analysis of sgk mutants
      revealed TPI impairment associated with reduced longevity, progressive locomotor
      deficiency, and neural degeneration. Biochemical studies demonstrate that
      mutation of this glycolytic enzyme gene does not result in a bioenergetic
      deficit, suggesting an alternate cause of enzymopathy associated with TPI
      impairment.

PMID- 16980389
TI  - SWAN-1, a Caenorhabditis elegans WD repeat protein of the AN11 family, is a
      negative regulator of Rac GTPase function.
AB  - Rac GTPases are key regulators of cell shape and cytoskeletal organization. While
      some regulators of Rac activity are known, such as GTPase-activating proteins
      (GAPs) that repress Rac activity, other Rac regulators remain to be identified.
      The novel Caenorhabditis elegans WD-repeat protein SWAN-1 was identified in a
      yeast two-hybrid screen with the LIM domains of the Rac effector UNC-115/abLIM.
      SWAN-1 was found to also associate physically with Rac GTPases. The swan-1(ok267)
      loss-of-function mutation suppressed defects caused by the hypomorphic ced
      10(n1993) allele and enhanced ectopic lamellipodia and filopodia formation
      induced by constitutively active Rac in C. elegans neurons. Furthermore, SWAN
      1(+) transgenic expression suppressed the effects of overactive Rac, including
      ectopic lamellipodia and filopodia formation in C. elegans neurons, ectopic
      lamellipodia formation in cultured mammalian fibroblasts, and cell polarity and
      actin cytoskeleton defects in yeast. These studies indicate that SWAN-1 is an
      inhibitor of Rac GTPase function in cellular morphogenesis and cytoskeletal
      organization. While broadly conserved across species, SWAN-1 family members show
      no sequence similarity to previously known Rac inhibitors.

PMID- 16980390
TI  - The Aspergillus nidulans rcoA gene is required for veA-dependent sexual
      development.
AB  - The Aspergillus nidulans rcoADelta mutant exhibits growth and developmental
      defects. We show that the rcoADelta mutant lacks cleistothecia and is self
      sterile. In crosses with wild-type strains, rcoADelta nuclei do not contribute to
      the cleistothecial walls. Furthermore, sexual development resulting from veA
      overexpression is rcoA dependent, indicating that rcoA lies downstream of veA in
      the sexual development pathway.

PMID- 16980391
TI  - Molecular-genetic biodiversity in a natural population of the yeast Saccharomyces
      cerevisiae from "Evolution Canyon": microsatellite polymorphism, ploidy and
      controversial sexual status.
AB  - The yeast S. cerevisiae is a central model organism in eukaryotic cell studies
      and a major component in many food and biotechnological industrial processes.
      However, the wide knowledge regarding genetics and molecular biology of S.
      cerevisiae is based on an extremely narrow range of strains. Studies of natural
      populations of S. cerevisiae, not associated with human activities or industrial
      fermentation environments, are very few. We isolated a panel of S. cerevisiae
      strains from a natural microsite, "Evolution Canyon" at Mount Carmel, Israel, and
      studied their genomic biodiversity. Analysis of 19 microsatellite loci revealed
      high allelic diversity and variation in ploidy level across the panel, from
      diploids to tetraploids, confirmed by flow cytometry. No significant differences
      were found in the level of microsatellite variation between strains derived from
      the major localities or microniches, whereas strains of different ploidy showed
      low similarity in allele content. Maximum genetic diversity was observed among
      diploids and minimum among triploids. Phylogenetic analysis revealed clonal,
      rather than sexual, structure of the triploid and tetraploid subpopulations.
      Viability tests in tetrad analysis also suggest that clonal reproduction may
      predominate in the polyploid subpopulations.

PMID- 16980392
TI  - The WTM genes in budding yeast amplify expression of the stress-inducible gene
      RNR3.
AB  - Cellular responses to DNA damage and inhibited replication are evolutionarily
      conserved sets of pathways that are critical to preserving genome stability. To
      identify new participants in these responses, we undertook a screen for
      regulators that, when present on a high-copy vector, alter expression of a DNA
      damage-inducible RNR3-lacZ reporter construct in Saccharomyces cerevisiae. From
      this screen we isolated a plasmid encoding two closely related paralogs, WTM1 and
      WTM2, that greatly increases constitutive expression of RNR3-lacZ. Moderate
      overexpression of both genes together, or high-level expression of WTM2 alone
      from a constitutive promoter, upregulates RNR3-lacZ in the absence of DNA damage.
      Overexpressed, tagged Wtm2p is associated with the RNR3 promoter, indicating that
      this effect is likely direct. Further investigation reveals that Wtm2p and Wtm1p,
      previously described as regulators of meiotic gene expression and transcriptional
      silencing, amplify transcriptional induction of RNR3 in response to replication
      stress and modulate expression of genes encoding other RNR subunits.

PMID- 16980393
TI  - Large-scale gene expression differences across brain regions and inbred strains
      correlate with a behavioral phenotype.
AB  - Behaviors are often highly heritable, polygenic traits. To investigate molecular
      mediators of behavior, we analyzed gene expression patterns across seven brain
      regions (amygdala, basal ganglia, cerebellum, frontal cortex, hippocampus,
      cingulate cortex, and olfactory bulb) of 10 different inbred mouse strains
      (129S1/SvImJ, A/J, AKR/J, BALB/cByJ, BTBR T+ tf/J, C3H/HeJ, C57BL/6J, C57L/J,
      DBA/2J, and FVB/NJ). Extensive variation was observed across both strain and
      brain region. These data provide potential transcriptional intermediates linking
      polygenic variation to differences in behavior. For example, mice from different
      strains had variable performance on the rotarod task, which correlated with the
      expression of >2000 transcripts in the cerebellum. Correlation with this task was
      also found in the amygdala and hippocampus, but not in other regions examined,
      indicating the potential complexity of motor coordination. Thus we can begin to
      identify expression profiles contributing to behavioral phenotypes through
      variation in gene expression.

PMID- 16980394
TI  - Glyceraldehyde-3-phosphate dehydrogenase mediates anoxia response and survival in
      Caenorhabditis elegans.
AB  - Oxygen deprivation has a role in the pathology of many human diseases. Thus it is
      of interest in understanding the genetic and cellular responses to hypoxia or
      anoxia in oxygen-deprivation-tolerant organisms such as Caenorhabditis elegans.
      In C. elegans the DAF-2/DAF-16 pathway, an IGF-1/insulin-like signaling pathway,
      is involved with dauer formation, longevity, and stress resistance. In this
      report we compared the response of wild-type and daf-2(e1370) animals to anoxia.
      Unlike wild-type animals, the daf-2(e1370) animals have an enhanced anoxia
      survival phenotype in that they survive long-term anoxia and high-temperature
      anoxia, do not accumulate significant tissue damage in either of these
      conditions, and are motile after 24 hr of anoxia. RNA interference was used to
      screen DAF-16-regulated genes that suppress the daf-2(e1370)-enhanced anoxia
      survival phenotype. We identified gpd-2 and gpd-3, two nearly identical genes in
      an operon that encode the glycolytic enzyme glyceraldehyde-3-phosphate
      dehydrogenase. We found that not only is the daf-2(e1370)-enhanced anoxia
      phenotype dependent upon gpd-2 and gpd-3, but also the motility of animals
      exposed to brief periods of anoxia is prematurely arrested in gpd-2/3(RNAi) and
      daf-2(e1370);gpd-2/3(RNAi) animals. These data suggest that gpd-2 and gpd-3 may
      serve a protective role in tissue exposed to oxygen deprivation.

PMID- 16980395
TI  - A gain-of-function screen identifying genes required for vein formation in the
      Drosophila melanogaster wing.
AB  - The formation of the Drosophila wing involves developmental processes such as
      cell proliferation, pattern formation, and cell differentiation that are common
      to all multicellular organisms. The genes controlling these cellular behaviors
      are conserved throughout the animal kingdom, and the genetic analysis of wing
      development has been instrumental in their identification and functional
      characterization. The wing is a postembryonic structure, and most loss-of
      function mutations are lethal in homozygous flies before metamorphosis. In this
      manner, loss-of-function genetic screens aiming to identify genes affecting wing
      formation have not been systematically utilized. As an alternative, a number of
      genetic searches have utilized the phenotypic consequences of gene gain-of
      expression, as a method more efficient to search for genes required during
      imaginal development. Here we present the results of a gain-of-function screen
      designed to identify genes involved in the formation of the wing veins. We
      generated 13,000 P-GS insertions of a P element containing UAS sequences (P-GS)
      and combined them with a Gal4 driver expressed mainly in the developing pupal
      veins. We selected 500 P-GSs that, in combination with the Gal4 driver, result in
      modifications of the veins, changes in the morphology of the wing, or defects in
      the differentiation of the trichomes. The P-element insertion sites were mapped
      to the genomic sequence, identifying 373 gene candidates to participate in wing
      morphogenesis and vein formation.

PMID- 16980396
TI  - Estimating recombination rates from single-nucleotide polymorphisms using summary
      statistics.
AB  - We describe a novel method for jointly estimating crossing-over and gene
      conversion rates from population genetic data using summary statistics. The
      performance of our method was tested on simulated data sets and compared with the
      composite-likelihood method of R. R. Hudson. For several realistic parameter
      values, the new method performed similarly to the composite-likelihood approach
      for estimating crossing-over rates and better when estimating gene-conversion
      rates. We used our method to analyze a human data set recently genotyped by
      Perlegen Sciences.

PMID- 16980397
TI  - A Thurstonian model for quantitative genetic analysis of ranks: a Bayesian
      approach.
AB  - A fully Bayesian method for quantitative genetic analysis of data consisting of
      ranks of, e.g., genotypes, scored at a series of events or experiments is
      presented. The model postulates a latent structure, with an underlying variable
      realized for each genotype or individual involved in the event. The rank observed
      is assumed to reflect the order of the values of the unobserved variables, i.e.,
      the classical Thurstonian model of psychometrics. Parameters driving the Bayesian
      hierarchical model include effects of covariates, additive genetic effects,
      permanent environmental deviations, and components of variance. A Markov chain
      Monte Carlo implementation based on the Gibbs sampler is described, and
      procedures for inferring the probability of yet to be observed future rankings
      are outlined. Part of the model is rendered nonparametric by introducing a
      Dirichlet process prior for the distribution of permanent environmental effects.
      This can lead to potential identification of clusters of such effects, which, in
      some competitions such as horse races, may reflect forms of undeclared
      preferential treatment.

PMID- 16980398
TI  - Nonneutral evolution of organelle genes in Silene vulgaris.
AB  - Knowledge of mitochondrial gene evolution in angiosperms has taken a dramatic
      shift within the past decade, from universal slow rates of nucleotide change to a
      growing realization of high variation in rates among lineages. Additionally,
      evidence of paternal inheritance of plant mitochondria and recombination among
      mitochondrial genomes within heteroplasmic individuals has led to speculation
      about the potential for independent evolution of organellar genes. We report
      intraspecific mitochondrial and chloroplast sequence variation in a cosmopolitan
      sample of 42 Silene vulgaris individuals. There was remarkably high variation in
      two mitochondrial genes (atp1, atp9) and additional variation within a third gene
      (cob). Tests for patterns of nonneutral evolution were significant for atp1 and
      atp9, indicative of the maintenance of balanced polymorphisms. Two chloroplast
      genes (matK, ndhF) possessed less, but still high, variation and no divergence
      from neutral expectations. Phylogenetic patterns of organelle genes in both the
      chloroplast and mitochondria were incongruent, indicating the potential for
      independent evolutionary trajectories. Evidence indicated reassociation among
      cytoplasmic genomes and recombination between mitochondrial genes and within
      atp1, implying transient heteroplasmy in ancestral lineages. Although the
      mechanisms for long-term maintenance of mitochondrial polymorphism are currently
      unknown, frequency-dependent selection on linked cytoplasmic male sterility genes
      is a potential candidate.

PMID- 16980399
TI  - Identification of a novel gene family involved in osmotic stress response in
      Caenorhabditis elegans.
AB  - Organisms exposed to the damaging effects of high osmolarity accumulate solutes
      to increase cytoplasmic osmolarity. Yeast accumulates glycerol in response to
      osmotic stress, activated primarily by MAP kinase Hog1 signaling. A pathway
      regulated by protein kinase C (PKC1) also responds to changes in osmolarity and
      cell wall integrity. C. elegans accumulates glycerol when exposed to high
      osmolarity, but the molecular pathways responsible for this are not well
      understood. We report the identification of two genes, osm-7 and osm-11, which
      are related members of a novel gene family. Mutations in either gene lead to high
      internal levels of glycerol and cause an osmotic resistance phenotype (Osr).
      These mutants also have an altered defecation rhythm (Dec). Mutations in cuticle
      collagen genes dpy-2, dpy-7, and dpy-10 cause a similar Osr Dec phenotype. osm-7
      is expressed in the hypodermis and may be secreted. We hypothesize that osm-7 and
      osm-11 interact with the cuticle, and disruption of the cuticle causes activation
      of signaling pathways that increase glycerol production. The phenotypes of osm-7
      are not suppressed by mutations in MAP kinase or PKC pathways, suggesting that C.
      elegans uses signaling pathways different from yeast to mount a response to
      osmotic stress.

PMID- 16980400
TI  - The large isoform of Drosophila melanogaster heterochromatin protein 2 plays a
      critical role in gene silencing and chromosome structure.
AB  - Drosophila melanogaster heterochromatin protein 2 (HP2) interacts with
      heterochromatin protein 1 (HP1). In polytene chromosomes, HP2 and HP1 colocalize
      at the chromocenter, telomeres, and the small fourth chromosome. We show here
      that HP2 is present in the arms as well as the centromeric regions of mitotic
      chromosomes. We also demonstrate that Su(var)2-HP2 exhibits a dosage-dependent
      modification of variegation of a yellow reporter transgene, indicating a
      structural role in heterochromatin formation. We have isolated and characterized
      14 new mutations in the Su(var)2-HP2 gene. Using wm4h, many (but not all) mutant
      alleles show dominant Su(var) activity. Su(var)2-HP2 mutant larvae show a wide
      variety of mitotic abnormalities, but not the telomere fusion seen in larvae
      deficient for HP1. The Su(var)2-HP2 gene codes for two isoforms: HP2-L
      (approximately 365 kDa) and HP2-S (approximately 175 kDa), lacking exons 5 and 6.
      In general, mutations that affect only the larger isoform result in more
      pronounced defects than do mutations common to both isoforms. This suggests that
      an imbalance between large and small isoforms is particularly deleterious. These
      results indicate a role for HP2 in the structural organization of chromosomes and
      in heterochromatin-induced gene silencing and show that the larger isoform plays
      a critical role in these processes.

PMID- 16980401
TI  - Test of association between haplotypes and phenotypes in case-control studies:
      examination of validity of the application of an algorithm for samples from
      cohort or clinical trials to case-control samples using simulated and real data.
AB  - The use of haplotype information in case-control studies is an area of focus for
      the research on the association between phenotypes and genetic polymorphisms. We
      examined the validity of the application of the likelihood-based algorithm, which
      was originally developed to analyze the data from cohort studies or clinical
      trials, to the data from case-control studies. This algorithm was implemented in
      a computer program called PENHAPLO. In this program, haplotype frequencies and
      penetrances are estimated using the expectation-maximization algorithm, and the
      haplotype-phenotype association is tested using the generalized likelihood ratio.
      We show that this algorithm was useful not only for cohort studies but also for
      case-control studies. Simulations under the null hypothesis (no association
      between haplotypes and phenotypes) have shown that the type I error rates were
      accurately estimated. The simulations under alternative hypotheses showed that
      PENHAPLO is a robust method for the analysis of the data from case-control
      studies even when the haplotypes were not in HWE, although real penetrances
      cannot be estimated. The power of PENHAPLO was higher than that of other methods
      using the likelihood-ratio test for the comparison of haplotype frequencies.
      Results of the analysis of real data indicated that a significant association
      between haplotypes in the SAA1 gene and AA-amyloidosis phenotype was observed in
      patients with rheumatoid arthritis, thereby suggesting the validity of the
      application of PENHAPLO for case-control data.

PMID- 16980403
TI  - Production of tyrosol by Candida albicans biofilms and its role in quorum sensing
      and biofilm development.
AB  - Tyrosol and farnesol are quorum-sensing molecules produced by Candida albicans
      which accelerate and block, respectively, the morphological transition from
      yeasts to hyphae. In this study, we have investigated the secretion of tyrosol by
      C. albicans and explored its likely role in biofilm development. Both planktonic
      (suspended) cells and biofilms of four C. albicans strains, including three
      mutants with defined defects in the Efg 1 and Cph 1 morphogenetic signaling
      pathways, synthesized extracellular tyrosol during growth at 37 degrees C. There
      was a correlation between tyrosol production and biomass for both cell types.
      However, biofilm cells secreted at least 50% more tyrosol than did planktonic
      cells when tyrosol production was related to cell dry weight. The addition of
      exogenous farnesol to a wild-type strain inhibited biofilm formation by up to 33%
      after 48 h. Exogenous tyrosol appeared to have no effect, but scanning electron
      microscopy revealed that tyrosol stimulated hypha production during the early
      stages (1 to 6 h) of biofilm development. Experiments involving the simultaneous
      addition of tyrosol and farnesol at different concentrations suggested that the
      action of farnesol was dominant, and 48-h biofilms formed in the presence of both
      compounds consisted almost entirely of yeast cells. When biofilm supernatants
      were tested for their abilities to inhibit or enhance germ tube formation by
      planktonic cells, the results indicated that tyrosol activity exceeds that of
      farnesol after 14 h, but not after 24 h, and that farnesol activity increases
      significantly during the later stages (48 to 72 h) of biofilm development.
      Overall, our results support the conclusion that tyrosol acts as a quorum-sensing
      molecule for biofilms as well as for planktonic cells and that its action is most
      significant during the early and intermediate stages of biofilm formation.

PMID- 16980402
TI  - A deletion at the mouse Xist gene exposes trans-effects that alter the
      heterochromatin of the inactive X chromosome and the replication time and DNA
      stability of both X chromosomes.
AB  - The inactive X chromosome of female mammals displays several properties of
      heterochromatin including late replication, histone H4 hypoacetylation, histone
      H3 hypomethylation at lysine-4, and methylated CpG islands. We show that cre-Lox
      mediated excision of 21 kb from both Xist alleles in female mouse fibroblasts led
      to the appearance of two histone modifications throughout the inactive X
      chromosome usually associated with euchromatin: histone H4 acetylation and
      histone H3 lysine-4 methylation. Despite these euchromatic properties, the
      inactive X chromosome was replicated even later in S phase than in wild-type
      female cells. Homozygosity for the deletion also caused regions of the active X
      chromosome that are associated with very high concentrations of LINE-1 elements
      to be replicated very late in S phase. Extreme late replication is a property of
      fragile sites and the 21-kb deletions destabilized the DNA of both X chromosomes,
      leading to deletions and translocations. This was accompanied by the
      phosphorylation of p53 at serine-15, an event that occurs in response to DNA
      damage, and the accumulation of gamma-H2AX, a histone involved in DNA repair, on
      the X chromosome. The Xist locus therefore maintains the DNA stability of both X
      chromosomes.

PMID- 16980404
TI  - Identification and biochemical characterization of serine hydroxymethyl
      transferase in the hydrogenosome of Trichomonas vaginalis.
AB  - Serine hydroxymethyl transferase (SHMT) is a pyridoxal phosphate (PLP)-dependent
      enzyme that catalyzes the reversible conversion of serine and tetrahydrofolate to
      glycine and methylenetetrahydrofolate. We have identified a single gene encoding
      SHMT in the genome of Trichomonas vaginalis, an amitochondriate, deep-branching
      unicellular protist. The protein possesses a putative N-terminal hydrogenosomal
      presequence and was shown to localize to hydrogensomes by immunofluorescence
      analysis, providing evidence of amino acid metabolism in this unusual organelle.
      In contrast to the tetrameric SHMT that exists in the mammalian host, we found
      that the T. vaginalis SHMT is a homodimer, as found in prokaryotes. All examined
      SHMT contain an 8-amino-acid conserved sequence, VTTTTHKT, containing the active
      site lysyl residue (Lys 251 in TvSHMT) that forms an internal aldimine with PLP.
      We mutated this Lys residue to Arg and Gln and examined structural and catalytic
      properties of the wild-type and mutant enzymes in comparison to that reported for
      the mammalian protein. The oligomeric structure of the mutant K251R and K251Q
      TvSHMT was not affected, in contrast to that observed for comparable mutations in
      the mammalian enzyme. Likewise, contrary to that observed for mammalian SHMT, the
      catalytic activity of K251R TvSHMT was unaffected in the presence of PLP. The
      K251Q TvSHMT, however, was found to be inactive. These studies indicate that the
      active site of the parasite enzyme is distinct from its prokaryotic and
      eukaryotic counterparts and identify TvSHMT as a potential drug target.

PMID- 16980405
TI  - Nitrogen availability and TOR regulate the Snf1 protein kinase in Saccharomyces
      cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, the Snf1 protein kinase of the Snf1/AMP
      activated protein kinase (AMPK) family regulates a wide range of responses to
      stress caused by glucose deprivation. The stress signal is relayed via
      upregulation of Snf1, which depends on phosphorylation of its activation loop
      Thr210 residue by upstream kinases. Although Snf1 is also required for coping
      with various stresses unrelated to glucose deprivation, some evidence suggests a
      role for low-level basal activity of unphosphorylated Snf1, rather than a
      specific signaling function. We previously found that Snf1 is required for
      diploid pseudohyphal differentiation, a developmental response to nitrogen
      limitation. Here, we present evidence that Snf1 is directly involved in nitrogen
      signaling. First, genetic analyses suggest that pseudohyphal differentiation
      depends on the stimulatory phosphorylation of Snf1 at Thr210. Second,
      immunochemical data indicate that nitrogen limitation improves Thr210
      phosphorylation. Analyses of pseudohyphal differentiation in cells with
      catalytically inactive and hyperactive Snf1 support the role of Snf1 activity.
      Finally, we show that Snf1 is negatively regulated by the rapamycin-sensitive TOR
      kinase which plays essential roles in signaling nitrogen and amino acid
      availability. This and other evidence implicate Snf1 in the integration of
      signals regarding nitrogen and carbon stress. TOR and Snf1/AMPK are highly
      conserved in evolution, and their novel functional interaction in yeast suggests
      similar mechanisms in other eukaryotes.

PMID- 16980406
TI  - Effect of sequence-directed nucleosome disruption on cell-type-specific
      repression by alpha2/Mcm1 in the yeast genome.
AB  - In Saccharomyces cerevisiae, a-cell-specific genes are repressed in MATalpha
      cells by alpha2/Mcm1, acting in concert with the Ssn6-Tup1 corepressors and the
      Isw2 chromatin remodeling complex, and nucleosome positioning has been proposed
      as one mechanism of repression. However, prior studies showed that nucleosome
      positioning is not essential for repression by alpha2/Mcm1 in artificial reporter
      plasmids, and the importance of the nucleosome positioning remains questionable.
      We have tested the function of positioned nucleosomes through alteration of
      genomic chromatin at the a-cell-specific gene BAR1. We report here that a
      positioned nucleosome in the BAR1 promoter is disrupted in cis by the insertion
      of diverse DNA sequences such as poly(dA) . poly(dT) and poly(dC-dG) . poly(dC
      dG), leading to inappropriate partial derepression of BAR1. Also, we show that
      isw2 mutation causes loss of nucleosome positioning in BAR1 in MATalpha cells as
      well as partial disruption of repression. Thus, nucleosome positioning is
      required for full repression, but loss of nucleosome positioning is not
      sufficient to relieve repression completely. Even though disruption of nucleosome
      positioning by the cis- and trans-acting modulators of chromatin has a modest
      effect on the level of transcription, it causes significant degradation of the
      alpha-mating pheromone in MATalpha cells, thereby affecting its cell type
      identity. Our results illustrate a useful paradigm for analysis of chromatin
      structural effects at genomic loci.

PMID- 16980407
TI  - Targeted deletion of MIC5 enhances trimming proteolysis of Toxoplasma invasion
      proteins.
AB  - Limited proteolysis of proteins transiently expressed on the surface of the
      opportunistic pathogen Toxoplasma gondii accompanies cell invasion and
      facilitates parasite migration across cell barriers during infection. However,
      little is known about what factors influence this specialized proteolysis or how
      these proteolytic events are regulated. Here we show that genetic ablation of the
      micronemal protein MIC5 enhances the normal proteolytic processing of several
      micronemal proteins secreted by Toxoplasma tachyzoites. Restoring MIC5 expression
      by genetic complementation reversed this phenotype, as did treatment with the
      protease inhibitor ALLN, which was previously shown to block the activity of a
      hypothetical parasite surface protease called MPP2. We show that, despite its
      lack of obvious membrane association signals, MIC5 occupies the parasite surface
      during invasion in the vicinity of the proteins affected by enhanced processing.
      Proteolysis of other secretory proteins, including GRA1, was also enhanced in
      MIC5 knockout parasites, indicating that the phenotype is not strictly limited to
      proteins derived from micronemes. Together, our findings suggest that MIC5 either
      directly regulates MPP2 activity or it influences MPP2's ability to access
      substrate cleavage sites on the parasite surface.

PMID- 16980408
TI  - Transducer of regulated CREB-binding proteins (TORCs) induce PGC-1alpha
      transcription and mitochondrial biogenesis in muscle cells.
AB  - PGC-1alpha (peroxisome proliferator-activated receptor gamma coactivator 1alpha)
      is a master regulator of mitochondrial biogenesis and plays an important role in
      several other aspects of energy metabolism. To identify upstream regulators of
      PGC-1alpha gene transcription, 10,000 human full-length cDNAs were screened for
      induction of the PGC-1alpha promoter. A number of activators of PGC-1alpha
      transcription were found; the most potent activator was the transducer of
      regulated CREB (cAMP response element-binding protein) binding protein (TORC) 1,
      a coactivator of CREB. The other two members of the TORC family, TORC2 and TORC3,
      also strongly activated PGC-1alpha transcription. TORCs dramatically induced PGC
      1alpha gene transcription through CREB. Forced expression of TORCs in primary
      muscle cells induced the endogenous mRNA of PGC-1alpha and its downstream target
      genes in the mitochondrial respiratory chain and TCA cycle. Importantly, these
      changes in gene expression resulted in increased mitochondrial oxidative capacity
      measured by cellular respiration and fatty acid oxidation. Finally, we
      demonstrated that the action of TORCs in promoting mitochondrial gene expression
      and function requires PGC-1alpha. Previous studies had indicated that TORCs
      function as a calcium- and cAMP-sensitive coincidence detector and mediate
      individual and synergistic effects of these two pathways. Our results, together
      with previous findings, strongly suggest that TORCs play a key role in linking
      these external signals to the transcriptional program of adaptive mitochondrial
      biogenesis by activating PGC-1alpha gene transcription.

PMID- 16980410
TI  - Partitioning of atmospherically relevant ions between bulk water and the
      water/vapor interface.
AB  - Recently, surface-sensitive spectroscopy data and molecular dynamics simulations
      have generated intense interest in the distribution of electrolyte ions between
      bulk water and the air/water interface. A partitioning model for cations and
      anions developed for biopolymer surface is extended here to interpret the effects
      of selected acids, bases, and salts on the surface tension of water. Data for
      electrolytes were analyzed by using a lower-bound value for the number of water
      molecules in the surface region [0.2 H(2)O A(-2) (approximately two layers of
      water)], obtained by assuming that both Na(+) and SO(4)(2-) (i.e., Na(2)SO(4))
      are fully excluded from this region. Surface-bulk partition coefficients of
      atmospherically relevant anions and the proton are determined. Notably, we find
      that H(+) is most strongly surface-accumulated, I(-) is modestly accumulated,
      NO(3)(-) is evenly distributed, and OH(-) is weakly excluded.

PMID- 16980409
TI  - Aberrant MHC class II expression in mouse joints leads to arthritis with
      extraarticular manifestations similar to rheumatoid arthritis.
AB  - Genetic susceptibility to rheumatoid arthritis (RA) is associated with certain
      MHC class II molecules. To clarify the role of these determinants in RA, we
      generated the D1CC transgenic mouse that expressed genes involved in antigen
      processing and presentation by the MHC class II pathway in joints. The class II
      transactivator, which was transcribed from the rat collagen type II promoter and
      enhancer, directed the expression of these genes. In D1CC mice congenic for the H
      2(q) (DBA/1) background, small amounts of bovine collagen type II in adjuvant
      induced reproducibly an inflammatory arthritis resembling RA. Importantly, these
      stimuli had no effect in DBA/1 mice. Eighty-nine percent of D1CC mice developed
      chronic disease with joint swelling, redness, and heat in association with
      synovial proliferation as well as pannus formation and mononuclear infiltration
      of synovial membranes. Granulomatous lesions resembling rheumatoid nodules and
      interstitial pneumonitis also were observed. As in patients with RA, anticyclic
      citrullinated peptide antibodies were detected during the inflammatory stage.
      Finally, joints in D1CC mice displayed juxtaarticular demineralization, severe
      joint space narrowing, and erosions, which led to ankylosis, but without the
      appearance of osteophytes. Thus, aberrant expression of MHC class II in joints
      facilitates the development of severe erosive inflammatory polyarthritis, which
      is very similar to RA.

PMID- 16980411
TI  - Granulocyte colony-stimulating factor preferentially stimulates proliferation of
      monosomy 7 cells bearing the isoform IV receptor.
AB  - Granulocyte colony-stimulating factor (GCSF) administration has been linked to
      the development of monosomy 7 in severe congenital neutropenia and aplastic
      anemia. We assessed the effect of pharmacologic doses of GCSF on monosomy 7 cells
      to determine whether this chromosomal abnormality developed de novo or arose as a
      result of favored expansion of a preexisting clone. Fluorescence in situ
      hybridization (FISH) of chromosome 7 was used to identify small populations of
      aneuploid cells. When bone marrow mononuclear cells from patients with monosomy 7
      were cultured with 400 ng/ml GCSF, all samples showed significant increases in
      the proportion of monosomy 7 cells. In contrast, bone marrow from karyotypically
      normal aplastic anemia, myelodysplastic syndrome, or healthy individuals did not
      show an increase in monosomy 7 cells in culture. In bone marrow CD34 cells of
      patients with myelodysplastic syndrome and monosomy 7, GCSF receptor (GCSFR)
      protein was increased. Although no mutation was found in genomic GCSFR DNA, CD34
      cells showed increased expression of the GCSFR class IV mRNA isoform, which is
      defective in signaling cellular differentiation. GCSFR signal transduction via
      the Jak/Stat system was abnormal in monosomy 7 CD34 cells, with increased
      phosphorylated signal transducer and activation of transcription protein, STAT1
      P, and increased STAT5-P relative to STAT3-P. Our results suggest that
      pharmacologic doses of GCSF increase the proportion of preexisting monosomy 7
      cells. The abnormal response of monosomy 7 cells to GCSF would be explained by
      the expansion of undifferentiated monosomy 7 clones expressing the class IV
      GCSFR, which is defective in signaling cell maturation.

PMID- 16980412
TI  - Visualizing odorant receptor trafficking in living cells down to the single
      molecule level.
AB  - Despite the importance of trafficking for regulating G protein-coupled receptor
      signaling, for many members of the seven transmembrane helix protein family, such
      as odorant receptors, little is known about this process in live cells. Here, the
      complete life cycle of the human odorant receptor OR17-40 was directly monitored
      in living cells by ensemble and single-molecule imaging, using a double-labeling
      strategy. While the overall, intracellular trafficking of the receptor was
      visualized continuously by using a GFP tag, selective imaging of cell surface
      receptors was achieved by pulse-labeling an acyl carrier protein tag. We found
      that OR17-40 efficiently translocated to the plasma membrane only at low
      expression, whereas at higher biosynthesis the receptor accumulated in
      intracellular compartments. Receptors in the plasma membrane showed high turnover
      resulting from constitutive internalization along the clathrin pathway, even in
      the absence of ligand. Single-molecule microscopy allowed monitoring of the
      early, dynamic processes in odorant receptor signaling. Although mobile receptors
      initially diffused either freely or within domains of various sizes, binding of
      an agonist or an antagonist increased partitioning of receptors into small
      domains of approximately 190 nm, which likely are precursors of clathrin-coated
      pits. The binding of a ligand, therefore, resulted in modulation of the
      continuous, constitutive internalization. After endocytosis, receptors were
      directed to early endosomes for recycling. This unique mechanism of continuous
      internalization and recycling of OR17-40 might be instrumental in allowing rapid
      recovery of odor perception.

PMID- 16980413
TI  - Endogenous retroviruses regulate periimplantation placental growth and
      differentiation.
AB  - Endogenous retroviruses (ERVs) are fixed and abundant in the genomes of
      vertebrates. Circumstantial evidence suggests that ERVs play a role in mammalian
      reproduction, particularly placental morphogenesis, because intact ERV envelope
      genes were found to be expressed in the syncytiotrophoblasts of human and mouse
      placenta and to elicit fusion of cells in vitro. We report here in vivo and in
      vitro experiments finding that the envelope of a particular class of ERVs of
      sheep, endogenous Jaagsiekte sheep retroviruses (enJSRVs), regulates
      trophectoderm growth and differentiation in the periimplantation conceptus
      (embryo/fetus and associated extraembryonic membranes). The enJSRV envelope gene
      is expressed in the trophectoderm of the elongating ovine conceptus after day 12
      of pregnancy. Loss-of-function experiments were conducted in utero by injecting
      morpholino antisense oligonucleotides on day 8 of pregnancy that blocked enJSRV
      envelope protein production in the conceptus trophectoderm. This approach
      retarded trophectoderm outgrowth during conceptus elongation and inhibited
      trophoblast giant binucleate cell differentiation as observed on day 16.
      Pregnancy loss was observed by day 20 in sheep receiving morpholino antisense
      oligonucleotides. In vitro inhibition of the enJSRV envelope reduced the
      proliferation of mononuclear trophectoderm cells isolated from day 15
      conceptuses. Consequently, these results demonstrate that the enJSRV envelope
      regulates trophectoderm growth and differentiation in the periimplantation ovine
      conceptus. This work supports the hypothesis that ERVs play fundamental roles in
      placental morphogenesis and mammalian reproduction.

PMID- 16980414
TI  - Normal-repeat-length polyglutamine peptides accelerate aggregation nucleation and
      cytotoxicity of expanded polyglutamine proteins.
AB  - The dependence of disease risk and age-of-onset on expanded CAG repeat length in
      diseases like Huntington's disease (HD) is well established and correlates with
      the repeat-length-dependent nucleation kinetics of polyglutamine (polyGln)
      aggregation. The wide variation in ages of onset among patients with the same
      repeat length, however, suggests a role for modifying factors. Here we describe
      the ability of normal-length polyGln repeat sequences to greatly accelerate the
      nucleation kinetics of an expanded polyGln peptide. We find that normal-length
      polyGln peptides enhance the in vitro nucleation kinetics of a Q(47) peptide in a
      concentration-dependent and repeat-length-dependent manner. In vivo, we show that
      coexpression of a Q(20) sequence in a Drosophila model of HD expressing Htt exon
      1 protein with an Q(93) repeat accelerates both aggregate formation and
      neurotoxicity. The accelerating effect of short polyGln peptides is attributable
      to the promiscuity of polyGln aggregate elongation and reflects the intimate
      relationship between nucleus formation and early elongation events in
      establishing nucleation kinetics. The results suggest that the overall state of
      the polyGln protein network in a cellular environment may have a profound effect
      on the toxic consequences of polyGln expansion and thus may serve as a genetic
      modifier of age of onset in HD.

PMID- 16980415
TI  - The mosaic nature of intergenic 16S-23S rRNA spacer regions suggests rRNA operon
      copy number variation in Clostridium difficile strains.
AB  - Clostridium difficile is a major spore-forming environmental pathogen that causes
      serious health problems in patients undergoing antibiotic therapy. Consequently,
      reliable and sensitive methods for typing individual strains are required for
      epidemiological and environmental studies. Ribotyping is generally considered the
      best method, but it fails to account for sequence diversity which might exist in
      intergenic 16S-23S rRNA spacer regions (ISRs) within and among strains of this
      organism. Therefore, this study was undertaken to compare the sequence of each
      individual ISR in five strains of C. difficile to explore the extent of this
      diversity and see whether such information might provide the basis for more
      sensitive and discriminatory strain typing methods. After targeted PCR
      amplification, cloning, and sequencing, the diversity of the ISRs was used as a
      measure of rRNA operon copy number. In C. difficile strains 630, ATCC 43593, A,
      and B, 11, 11, 7, and 8 ISR length variants, respectively, were found (containing
      different combinations of sequence groups [i to xiii]), suggesting 11, 11, 7, and
      8 rrn copies in the respective strains. Many ISRs of the same length differed
      markedly in their sequences, and some of these were restricted in occurrence to a
      single strain. Most of these ISRs did not contain any tRNA genes, and only single
      copies of the tRNA(Ala) gene were found in those that did. The presence of ISR
      sequence groups (i to xiii) varied between strains, with some found in one, two,
      three, four, or all five strains. We conclude that the intergenic 16S-23S rRNA
      spacer regions showed a high degree of diversity, not only among the rrn operons
      in different strains and different rrn copies in a single strain but also among
      ISRs of the same length. It appears that C. difficile ISRs vary more at the inter
      and intragenic levels than those of other species as determined by empirical
      comparison of sequences. The precise characterization of these sequences has
      demonstrated a high level of mosaic sequence block rearrangements that are
      present or absent in multiple strain-variable rrn copies within and between five
      different strains of C. difficile.

PMID- 16980417
TI  - Examination of the watershed-wide distribution of Escherichia coli along Southern
      Lake Michigan: an integrated approach.
AB  - Recent research has highlighted the occurrence of Escherichia coli in natural
      habitats not directly influenced by sewage inputs. Most studies on E. coli in
      recreational water typically focus on discernible sources (e.g., effluent
      discharge and runoff) and fall short of integrating riparian, nearshore, onshore,
      and outfall sources. An integrated "beachshed" approach that links E. coli inputs
      and interactions would be helpful to understand the difference between background
      loading and sewage pollution; to develop more accurate predictive models; and to
      understand the differences between potential, net, and apparent culturable E.
      coli. The objective of this study was to examine the interrelatedness of E. coli
      occurrence from various coastal watershed components along southern Lake
      Michigan. The study shows that once established in forest soil, E. coli can
      persist throughout the year, potentially acting as a continuous non-point source
      of E. coli to nearby streams. Year-round background stream loading of E. coli can
      influence beach water quality. E. coli is present in highly variable counts in
      beach sand to depths just below the water table and to distances at least 5 m
      inland from the shore, providing a large potential area of input to beach water.
      In summary, E. coli in the fluvial-lacustrine system may be stored in forest
      soils, sediments surrounding springs, bank seeps, stream margins and pools,
      foreshore sand, and surface groundwater. While rainfall events may increase E.
      coli counts in the foreshore sand and lake water, concentrations quickly decline
      to prerain concentrations. Onshore winds cause an increase in E. coli in shallow
      nearshore water, likely resulting from resuspension of E. coli-laden beach sand.
      When examining indicator bacteria source, flux, and context, the entire
      "beachshed" as a dynamic interacting system should be considered.

PMID- 16980416
TI  - Increased abundance of IncP-1beta plasmids and mercury resistance genes in
      mercury-polluted river sediments: first discovery of IncP-1beta plasmids with a
      complex mer transposon as the sole accessory element.
AB  - Although it is generally assumed that mobile genetic elements facilitate the
      adaptation of microbial communities to environmental stresses, environmental data
      supporting this assumption are rare. In this study, river sediment samples taken
      from two mercury-polluted (A and B) and two nonpolluted or less-polluted (C and
      D) areas of the river Nura (Kazakhstan) were analyzed by PCR for the presence and
      abundance of mercury resistance genes and of broad-host-range plasmids. PCR-based
      detection revealed that mercury pollution corresponded to an increased abundance
      of mercury resistance genes and of IncP-1beta replicon-specific sequences
      detected in total community DNA. The isolation of IncP-1beta plasmids from
      contaminated sediments was attempted in order to determine whether they carry
      mercury resistance genes and thus contribute to an adaptation of bacterial
      populations to Hg pollution. We failed to detect IncP-1beta plasmids in the
      genomic DNA of the cultured Hg-resistant bacterial isolates. However, without
      selection for mercury resistance, three different IncP-1beta plasmids (pTP6,
      pTP7, and pTP8) were captured directly from contaminated sediment slurry in
      Cupriavidus necator JMP228 based on their ability to mobilize the IncQ plasmid
      pIE723. These plasmids hybridized with the merRTDeltaP probe and conferred Hg
      resistance to their host. A broad host range and high stability under conditions
      of nonselective growth were observed for pTP6 and pTP7. The full sequence of
      plasmid pTP6 was determined and revealed a backbone almost identical to that of
      the IncP-1beta plasmids R751 and pB8. However, this is the first example of an
      IncP-1beta plasmid which had acquired only a mercury resistance transposon but no
      antibiotic resistance or biodegradation genes. This transposon carries a rather
      complex set of mer genes and is inserted between Tra1 and Tra2.

PMID- 16980418
TI  - Toward a more robust assessment of intraspecies diversity, using fewer genetic
      markers.
AB  - Phylogenetic sequence analysis of single or multiple genes has dominated the
      study and census of the genetic diversity among closely related bacteria. It
      remains unclear, however, how the results based on a few genes in the genome
      correlate with whole-genome-based relatedness and what genes (if any) best
      reflect whole-genome-level relatedness and hence should be preferentially used to
      economize on cost and to improve accuracy. We show here that phylogenies of
      closely related organisms based on the average nucleotide identity (ANI) of their
      shared genes correspond accurately to phylogenies based on state-of-the-art
      analysis of their whole-genome sequences. We use ANI to evaluate the phylogenetic
      robustness of every gene in the genome and show that almost all core genes,
      regardless of their functions and positions in the genome, offer robust
      phylogenetic reconstruction among strains that show 80 to 95% ANI (16S rRNA
      identity, >98.5%). Lack of elapsed time and, to a lesser extent, horizontal
      transfer and recombination make the selection of genes more critical for
      applications that target the intraspecies level, i.e., strains that show >95% ANI
      according to current standards. A much more accurate phylogeny for the
      Escherichia coli group was obtained based on just three best-performing genes
      according to our analysis compared to the concatenated alignment of eight genes
      that are commonly employed for phylogenetic purposes in this group. Our results
      are reproducible within the Salmonella, Burkholderia, and Shewanella groups and
      therefore are expected to have general applicability for microevolution studies,
      including metagenomic surveys.

PMID- 16980419
TI  - Enhancement of chilling resistance of inoculated grapevine plantlets with a plant
      growth-promoting rhizobacterium, Burkholderia phytofirmans strain PsJN.
AB  - In vitro inoculation of Vitis vinifera L. cv. Chardonnay explants with a plant
      growth-promoting rhizobacterium, Burkholderia phytofirmans strain PsJN, increased
      grapevine growth and physiological activity at a low temperature. There was a
      relationship between endophytic bacterial colonization of the grapevine plantlets
      and their growth at both ambient (26 degrees C) and low (4 degrees C)
      temperatures and their sensitivities to chilling. The major benefits of
      bacterization were observed on root growth (11.8- and 10.7-fold increases at 26
      degrees C and 4 degrees C, respectively) and plantlet biomass (6- and 2.2-fold
      increases at 26 degrees C and 4 degrees C, respectively). The inoculation with
      PsJN also significantly improved plantlet cold tolerance compared to that of the
      nonbacterized control. In nonchilled plantlets, bacterization enhanced CO(2)
      fixation and O(2) evolution 1.3 and 2.2 times, respectively. The nonbacterized
      controls were more sensitive to exposure to low temperatures than were the
      bacterized plantlets, as indicated by several measured parameters. Moreover,
      relative to the noninoculated controls, bacterized plantlets had significantly
      increased levels of starch, proline, and phenolics. These increases correlated
      with the enhancement of cold tolerance of the grapevine plantlets. In summary, B.
      phytofirmans strain PsJN inoculation stimulates grapevine growth and improves its
      ability to withstand cold stress.

PMID- 16980420
TI  - The lantibiotic mersacidin is an autoinducing peptide.
AB  - The lantibiotic (lanthionine-containing antibiotic) mersacidin is an
      antimicrobial peptide consisting of 20 amino acids and is produced by Bacillus
      sp. strain HIL Y-85,54728. The structural gene (mrsA) and the genes for producer
      self-protection, modification enzymes, transport proteins, and regulator proteins
      are organized in a 12.3-kb biosynthetic gene cluster on the chromosome of the
      producer strain. Mersacidin is produced in stationary phase in a synthetic medium
      (K. Altena, A. Guder, C. Cramer, and G. Bierbaum, Appl. Environ. Microbiol.
      66:2565-2571, 2000). To investigate the influence of the alternative sigma factor
      H on mersacidin biosynthesis, a SigH knockout was constructed. The knockout
      mutant was asporogenous, and a comparison to the wild-type strain indicated no
      significant differences concerning mersacidin production and immunity.
      Characterization of the mrsA promoter showed that the gene is transcribed by the
      housekeeping sigma factor A. The biosynthesis of some lantibiotic peptides like
      nisin or subtilin is regulated in a cell-density-dependent manner (M.
      Kleerebezem, Peptides 25:1405-1414, 2004). When mersacidin was added at a
      concentration of 2 mg/liter to an exponentially growing culture, an earlier
      production of antibacterial activity against Micrococcus luteus ATCC 4698 in
      comparison to that of the control culture was observed, suggesting that
      mersacidin itself functions as an autoinducer. In real-time PCR experiments, the
      expression of mrsA was remarkably increased in the induced culture compared to
      the control. In conclusion, mersacidin is yet another lantibiotic peptide whose
      biosynthesis can be regulated by an autoinducing mechanism.

PMID- 16980421
TI  - A naturally occurring novel allele of Escherichia coli outer membrane protein A
      reduces sensitivity to bacteriophage.
AB  - A novel Escherichia coli outer membrane protein A (OmpA) was discovered through a
      proteomic investigation of cell surface proteins. DNA polymorphisms were
      localized to regions encoding the protein's surface-exposed loops which are known
      phage receptor sites. Bacteriophage sensitivity testing indicated an association
      between bacteriophage resistance and isolates having the novel ompA allele.

PMID- 16980422
TI  - The surfactant tween 80 enhances biodesulfurization.
AB  - In biocatalytic conversions, substrates and products may display inhibitory or
      toxic effects on the biocatalyst. Rhodococcus erythropolis 1awq could further
      remove sulfur from hydrodesulfurized diesel oil, and the biodesulfurization was
      enhanced by the surfactant Tween 80. Tween 80 was shown to decrease the product
      concentration associated with the cells, reducing product inhibition.

PMID- 16980423
TI  - Degradation of fluorobenzene by Rhizobiales strain F11 via ortho cleavage of 4
      fluorocatechol and catechol.
AB  - The aerobic metabolism of fluorobenzene by Rhizobiales sp. strain F11 was
      investigated. Liquid chromatography-mass spectrometry analysis showed that 4
      fluorocatechol and catechol were formed as intermediates during fluorobenzene
      degradation by cell suspensions. Both these compounds, unlike 3-fluorocatechol,
      supported growth and oxygen uptake. Cells grown on fluorobenzene contained
      enzymes for the ortho pathway but not for meta ring cleavage of catechols. The
      results suggest that fluorobenzene is predominantly degraded via 4-fluorocatechol
      with subsequent ortho cleavage and also partially via catechol.

PMID- 16980424
TI  - Cell surface expression of bacterial esterase A by Saccharomyces cerevisiae and
      its enhancement by constitutive activation of the cellular unfolded protein
      response.
AB  - Yeast cell surface display is a powerful tool for expression and immobilization
      of biocatalytically active proteins on a unicellular eukaryote. Here bacterial
      carboxylesterase EstA from Burkholderia gladioli was covalently anchored into the
      cell wall of Saccharomyces cerevisiae by in-frame fusion to the endogenous yeast
      proteins Kre1p, Cwp2p, and Flo1p. When p-nitrophenyl acetate was used as a
      substrate, the esterase specific activities of yeast expressing the protein
      fusions were 103 mU mg(-1) protein for Kre1/EstA/Cwp2p and 72 mU mg(-1) protein
      for Kre1/EstA/Flo1p. In vivo cell wall targeting was confirmed by esterase
      solubilization after laminarinase treatment and immunofluorescence microscopy.
      EstA expression resulted in cell wall-associated esterase activities of 2.72 U
      mg(-1) protein for Kre1/EstA/Cwp2p and 1.27 U mg(-1) protein for Kre1/EstA/Flo1p.
      Furthermore, esterase display on the yeast cell surface enabled the cells to
      effectively grow on the esterase-dependent carbon source glycerol triacetate
      (Triacetin). In the case of Kre1/EstA/Flo1p, in vivo maturation within the yeast
      secretory pathway and final incorporation into the wall were further enhanced
      when there was constitutive activation of the unfolded protein response pathway.
      Our results demonstrate that esterase cell surface display in yeast, which, as
      shown here, is remarkably more effective than EstA surface display in Escherichia
      coli, can be further optimized by activating the protein folding machinery in the
      eukaryotic secretion pathway.

PMID- 16980425
TI  - Occurrence and antibiotic sensitivity of Listeria monocytogenes strains isolated
      from oysters, fish, and estuarine water.
AB  - We analyzed the presence of Listeria spp. in oyster, fish, and seawater samples
      and tested isolates for antibiotic sensitivity. Listeria monocytogenes was found
      in 4.5% of fish samples and 8.3% of seawater samples and was not recovered from
      oysters. Multiresistant environmental strains were found, representing a
      potential threat to human health.

PMID- 16980426
TI  - Temporal and spatial dispersal of cladobotryum conidia in the controlled
      environment of a mushroom growing room.
AB  - Cladobotryum spp. are responsible for cobweb disease of mushrooms. In two
      commercial and one experimental mushroom-growing room, Cladobotryum conidia were
      released into the air in direct response to physical disturbance of disease
      colonies during either crop watering or treatment by covering with salt to 10 mm.
      Conidia were detected using a Burkard spore trap or agar-based trap plates. A
      maximum concentration of approximately 25,000 conidia m(-3) was recorded in a
      small (75-m(3)) experimental growing room in the hour following the salting of 16
      cobweb patches (0.55 m(2)). Concentrations of 100 and 40 conidia m(-3) were
      recorded in the two larger commercial growing rooms in the hour following the
      salting of 18 and 11 patches of cobweb (diameter, approximately 50 to 200 mm),
      respectively. In controlled experiments, disturbed conidia were dispersed rapidly
      throughout a small growing room, with 91 to 97% of conidia settling out within 15
      min. Eighty-five percent of conidia settled out within a 0.5-m radius when air
      conditioning fans were switched off, consistent with airborne spore dispersal.
      Alternative methods for treating diseased areas to minimize conidial release and
      distribution were investigated and included covering disease colonies with damp
      paper tissue prior to salt application (tissue salting) and holding a dust
      extractor above disease colonies during salt application. Both methods resulted
      in no detectable airborne conidia, but the tissue paper salting technique was
      more convenient. Prevention of airborne conidial release and distribution is
      essential to avoid mushroom spotting symptoms, secondary colonies, and early crop
      termination.

PMID- 16980427
TI  - Fermentation of high concentrations of maltose by Saccharomyces cerevisiae is
      limited by the COMPASS methylation complex.
AB  - In Saccharomyces cerevisiae, genes encoding maltose permeases and maltases are
      located in the telomeric regions of different chromosomes. The COMPASS
      methylation complex, which methylates lysine 4 on histone H3, controls the
      silencing of telomeric regions. Yeast strains deleted for SWD1, SWD3, SDC1, SET1,
      BRE2, or SPP1, encoding components of the COMPASS complex, fermented a medium
      containing 22% maltose with noticeably higher attenuation than did the wild type,
      resulting in production of up to 29% more ethanol. The least effective strain was
      spp1. Absence of COMPASS components had no effect on the fermentation of media
      with 20% glucose, 20% sucrose, or 16% maltose. Deletion of SWD3 resulted in
      larger amounts of MAL12 transcript, encoding maltase, at the late stages of
      fermentation of 22% maltose. A similar effect on maltase activity and maltose
      uptake capability was seen. The lysine 4 residue of histone H3 was trimethylated
      in wild-type cells at the late stages, while only small amounts of the
      dimethylated form were detected. Trimethylation and dimethylation of this residue
      were not detected in strains deleted for SWD1, SWD3, SET1, BRE2, or SDC1.
      Trimethylated lysine 4 was apparent only at the early stages (48 and 96 h) of
      fermentation in an spp1 strain. This work indicates that the COMPASS complex
      represses the expression of maltose utilization genes during the late stages of
      fermentation of a high concentration of maltose.

PMID- 16980428
TI  - An anaerobic methane-oxidizing community of ANME-1b archaea in hypersaline Gulf
      of Mexico sediments.
AB  - Sediments overlying a brine pool methane seep in the Gulf of Mexico (Green Canyon
      205) were analyzed using molecular and geochemical approaches to identify
      geochemical controls on microbial community composition and stratification. 16S
      rRNA gene and rRNA clone libraries, as well as mcrA gene clone libraries, showed
      that the archaeal community consists predominantly of ANME-1b methane oxidizers;
      no archaea of other ANME subgroups were found with general and group-specific PCR
      primers. The ANME-1b community was found in the sulfate-methane interface, where
      undersaturated methane concentrations of ca. 100 to 250 microM coexist with
      sulfate concentrations around 10 mM. Clone libraries of dsrAB genes and bacterial
      16S rRNA genes show diversified sulfate-reducing communities within and above the
      sulfate-methane interface. Their phylogenetic profiles and occurrence patterns
      are not linked to ANME-1b populations, indicating that electron donors other than
      methane, perhaps petroleum-derived hydrocarbons, drive sulfate reduction. The
      archaeal component of anaerobic oxidation of methane is comprised of an active
      population of mainly ANME-1b in this hypersaline sediment.

PMID- 16980429
TI  - Sensitivity of an immunomagnetic-separation-based test for detecting Escherichia
      coli O26 in bovine feces.
AB  - The sensitivity of a test for cattle shedding Escherichia coli serogroup O26 was
      estimated using several fecal pats artificially inoculated at a range of
      concentrations with different E. coli O26 strains. The test involves the
      enrichment of fecal microflora in buffered peptone water, the selective
      concentration of E. coli O26 using antibody-coated immunomagnetic-separation
      beads, the identification of E. coli colonies on Chromocult tryptone bile X
      glucuronide agar, and confirmation of the serogroup with E. coli serogroup O26
      specific antisera using slide agglutination. The effective dose of E. coli O26
      for an 80% test sensitivity (ED(80)) was 1.0 x 10(4) CFU g(-1) feces (95%
      confidence interval, 4.7 x 10(3) to 2.4 x 10(4)). Differences in test sensitivity
      between different E. coli O26 strains and fecal pats were also observed.
      Individual estimates of ED(80) for each strain and fecal pat combination ranged
      from 4.2 x 10(2) to 4.8 x 10(5) CFU g(-1). These results suggest that the test is
      useful for identifying individuals shedding a large number of E. coli O26
      organisms or, if an appropriate number of individuals in a herd are sampled, for
      identifying affected herds. The study also provides a benchmark estimate of
      sensitivity that can be used to compare alternative tests for E. coli O26 and a
      methodological approach that can be applied to tests for other pathogenic members
      of the Enterobacteriaceae and other sample types.

PMID- 16980430
TI  - Quantitative detection of hepatitis a virus and enteroviruses near the United
      States-Mexico border and correlation with levels of fecal indicator bacteria.
AB  - For decades, untreated sewage flowing northward from Tijuana, Mexico, via the
      Tijuana River has adversely affected the water quality of the recreational
      beaches of San Diego, California. We used quantitative reverse transcription-PCR
      to measure the levels of hepatitis A virus (HAV) and enteroviruses in coastal
      waters near the United States-Mexico border and compared these levels to those of
      the conventional fecal indicators, Escherichia coli and enterococci. Over a 2
      year period from 2003 to 2005, a total of 20 samples were assayed at two sites
      during both wet and dry weather: the surfzone at the mouth of the Tijuana River
      and the surfzone near the pier at Imperial Beach (IB), California (about 2 km
      north of the mouth of the Tijuana River). HAV and enterovirus were detected in 79
      and 93% of the wet-weather samples, respectively. HAV concentrations in these
      samples ranged from 105 to 30,771 viral particles/liter, and enterovirus levels
      ranged from 7 to 4,417 viral particles/liter. The concentrations of HAV and
      enterovirus were below the limit of detection for all dry weather samples
      collected at IB. Regression analyses showed a significant correlation between the
      densities of both fecal bacterial indicators and the levels of HAV (R2>0.61,
      P<0.0001) and enterovirus (R2>0.70, P<0.0001), a finding that supports the use of
      conventional bacterial indicators to predict the levels of these viruses in
      recreational marine waters.

PMID- 16980431
TI  - Validation of a green fluorescent protein-labeled strain of Vibrio vulnificus for
      use in the evaluation of postharvest strategies for handling of raw oysters.
AB  - In this paper we describe a biological indicator which can be used to study the
      behavior of Vibrio vulnificus, an important molluscan shellfish-associated human
      pathogen. A V. vulnificus ATCC 27562 derivative that expresses green fluorescent
      protein (GFP) and kanamycin resistance was constructed using conjugation. Strain
      validation was performed by comparing the GFP-expressing strain (Vv-GFP) and the
      wild-type strain (Vv-WT) with respect to growth characteristics, heat tolerance
      (45 degrees C), freeze-thaw tolerance (-20(o) and -80 degrees C), acid tolerance
      (pH 5.0, 4.0, and 3.5), cold storage tolerance (5 degrees C), cold adaptation (15
      degrees C), and response to starvation. Levels of recovery were evaluated using
      nonselective medium (tryptic soy agar containing 2% NaCl) with and without sodium
      pyruvate. The indicator strain was subsequently used to evaluate the survival of
      V. vulnificus in oysters exposed to organic acids (citric and acetic acids) and
      various cooling regimens. In most cases, Vv-GFP was comparable to Vv-WT with
      respect to growth and survival upon exposure to various biological stressors;
      when differences between the GFP-expressing and parent strains occurred, they
      usually disappeared when sodium pyruvate was added to media. When V. vulnificus
      was inoculated into shellstock oysters, the counts dropped 2 log(10) after 11 to
      12 days of refrigerated storage, regardless of the way in which the oysters were
      initially cooled. Steeper population declines after 12 days of refrigerated
      storage were observed for both iced and refrigerated products than for slowly
      cooled product and product held under conservative harvest conditions. By the end
      of the refrigeration storage study (22 days), the counts of Vv-GFP in iced and
      refrigerated oysters had reached the limit of detection (10(2) CFU/oyster), but
      slowly cooled oysters and oysters stored under conservative harvest conditions
      still contained approximately 10(3) and >10(4) CFU V. vulnificus/oyster by day
      22, respectively. The Vv-GFP levels in the oyster meat remained stable for up to
      24 h when the meat was exposed to acidic conditions at various pH values. Ease of
      detection and comparability to the wild-type parent make Vv-GFP a good candidate
      for use in studying the behavior of V. vulnificus upon exposure to sublethal
      stressors that might be encountered during postharvest handling of molluscan
      shellfish.

PMID- 16980432
TI  - Lactobacillus rhamnosus strain GG modulates intestinal absorption, fecal
      excretion, and toxicity of aflatoxin B(1) in rats.
AB  - In this study, the modulation of aflatoxin B(1) (AFB(1)) uptake in rats by
      administration of the probiotic Lactobacillus rhamnosus GG was demonstrated.
      Fecal AFB(1) excretion in GG-treated rats was increased via bacterial AFB(1)
      binding. Furthermore, AFB(1)-associated growth faltering and liver injury were
      alleviated with GG treatment.

PMID- 16980433
TI  - Environmental factors that affect the survival and persistence of Burkholderia
      pseudomallei.

PMID- 16980434
TI  - The SPI1 gene, encoding a glycosylphosphatidylinositol-anchored cell wall
      protein, plays a prominent role in the development of yeast resistance to
      lipophilic weak-acid food preservatives.
AB  - The Saccharomyces cerevisiae SPI1 gene encodes a member of the
      glycosylphosphatidylinositol-anchored cell wall protein family. In this work we
      show results indicating that SPI1 expression protects the yeast cell from damage
      caused by weak acids used as food preservatives. This is documented by a less
      extended period of adaptation to growth in their presence and by a less inhibited
      specific growth rate for a parental strain compared with a mutant with SPI1
      deleted. Maximal protection exerted by Spi1p against equivalent concentrations of
      the various weak acids tested was registered for the more lipophilic acids
      (octanoic acid, followed by benzoic acid) and was minimal for acetic acid. Weak
      acid adaptation was found to involve the rapid activation of SPI1 transcription,
      which is dependent on the presence of the Msn2p transcription factor. Activation
      of SPI1 transcription upon acetic acid stress also requires Haa1p, whereas this
      recently described transcription factor has a negligible role in the adaptive
      response to benzoic acid. The expression of SPI1 was found to play a prominent
      role in the development of yeast resistance to 1,3-beta-glucanase in benzoic acid
      stressed cells, while its involvement in acetic acid-induced resistance to the
      cell wall-lytic enzyme is slighter. The results are consistent with the notion
      that Spi1p expression upon weak-acid stress leads to cell wall remodeling,
      especially for the more lipophilic acids, decreasing cell wall porosity.
      Decreased cell wall porosity, in turn, reduces access to the plasma membrane,
      reducing membrane damage, intracellular acidification, and viability loss.

PMID- 16980435
TI  - Activation of endothelial nitric oxide synthase by the angiotensin II type 1
      receptor.
AB  - Enhanced angiotensin II (AngII) action has been implicated in endothelial
      dysfunction that is characterized as decreased nitric oxide availability.
      Although endothelial cells have been reported to express AngII type 1 (AT1)
      receptors, the exact role of AT1 in regulating endothelial NO synthase (eNOS)
      activity remains unclear. We investigated the possible regulation of eNOS through
      AT1 in bovine aortic endothelial cells (BAECs) and its functional significance in
      rat aortic vascular smooth muscle cells (VSMCs). In BAECs infected with
      adenovirus encoding AT1 and in VSMCs infected with adenovirus encoding eNOS,
      AngII rapidly stimulated phosphorylation of eNOS at Ser1179. This was accompanied
      with increased cGMP production. These effects were blocked by an AT1 antagonist.
      The cGMP production was abolished by a NOS inhibitor as well. To explore the
      importance of eNOS phosphorylation, VSMCs were also infected with adenovirus
      encoding S1179A-eNOS. AngII did not stimulate cGMP production in VSMCs expressing
      S1179A. However, S1179A was able to enhance basal NO production as confirmed with
      cGMP production and enhanced vasodilator-stimulated phosphoprotein
      phosphorylation. Interestingly, S1179A prevented the hypertrophic response
      similar to wild type in VSMCs. From these data, we conclude that the AngII/AT1
      system positively couples to eNOS via Ser1179 phosphorylation in ECs and VSMCs if
      eNOS and AT1 coexist. However, basal level NO production may be sufficient for
      prevention of AngII-induced hypertrophy by eNOS expression. These data
      demonstrate a novel molecular mechanism of eNOS regulation and function and thus
      provide useful information for eNOS gene therapy under endothelial dysfunction.

PMID- 16980436
TI  - Improved metabolic stimulus for glucose-induced insulin secretion through GK and
      PFK-2/FBPase-2 coexpression in insulin-producing RINm5F cells.
AB  - The glucose sensor enzyme glucokinase plays a pivotal role in the regulation of
      glucose-induced insulin secretion in pancreatic beta-cells. Activation of
      glucokinase represents a promising concept for the treatment of type 2 diabetes.
      Therefore, we analyzed the glucokinase activation through its physiological
      interaction partner, the bifunctional enzyme 6-phosphofructo-2-kinase/fructose
      2,6-bisphosphatase (PFK-2/FBPase-2) and the resulting effect on glucose
      metabolism in insulin-producing cells. In RINm5F-GK-PFK-2/FBPase-2 cells stably
      overexpressing glucokinase plus islet PFK-2/FBPase-2, colocalization between both
      enzymes as well as elevation of glucokinase activity were significantly increased
      at a stimulatory glucose concentration of 10 mmol/liter. RINm5F-GK-PFK-2/FBPase-2
      cells showed under this culture condition a significant increase in glucose
      utilization and in the ATP/ADP ratio compared with RINm5F-GK cells, which only
      overexpress glucokinase. Also glucose-induced insulin secretion was elevated in
      RINm5F-GK-PFK-2/FBPase-2 cells in comparison to RINm5F-GK cells. Furthermore,
      pyruvate accumulation and lactate production in RINm5F-GK-PFK-2/FBPase-2 cells
      were significantly lower at both 10 and 30 mmol/liter glucose than in RINm5F-GK
      and RINm5F cells. The significant improvement of glucose metabolism after PFK
      2/FBPase-2 overexpression is apparently not exclusively the result of high
      glucokinase enzyme activity. Stabilization of the closed glucokinase conformation
      by PFK-2/FBPase-2 may not only activate the enzyme but also improve metabolic
      channeling in beta-cells.

PMID- 16980437
TI  - Decreased brown adipocyte recruitment and thermogenic capacity in mice with
      impaired peroxisome proliferator-activated receptor (P465L PPARgamma) function.
AB  - Mice with a dominant-negative peroxisome proliferator-activated receptor gamma
      (PPARgamma) mutation (P465L) unexpectedly had normal amounts of adipose tissue.
      Here, we investigate the adipose tissue of the PPARgamma P465L mouse in detail.
      Microscopic analysis of interscapular adipose tissue of P465L PPARgamma mice
      revealed brown adipocytes with larger unilocular lipid droplets, indicative of
      reduced thermogenic capacity. Under conditions of cold exposure, the brown
      adipose tissue of the PPARgamma P465L mice was less active, a fact reflected in
      decreased uncoupling protein 1 levels. Analysis of the white adipocytes confirmed
      their normal cytoarchitecture and development, yet classical white adipose depots
      of the P465L PPARgamma mice had a striking reduction in brown adipocyte
      recruitment, a finding supported by reduced expression of UCP1 in the perigonadal
      adipose depot. Taken together, these data suggest that whole animal impairment of
      PPARgamma alters the cellular composition of the adipose organ to a more "white"
      adipose phenotype. Physiologically, this impairment in brown adipocyte
      recruitment is associated with decreased nonshivering thermogenic capacity after
      cold acclimation as revealed by norepinephrine responsiveness. Our results
      indicate that maintenance of oxidative brown-like adipose tissue is more
      dependent on PPARgamma function for development than white adipose tissue, an
      observation that may be relevant when considering PPARgamma-dependent strategies
      for the treatment of obesity.

PMID- 16980438
TI  - Overlapping and distinct expression of progesterone receptors A and B in mouse
      uterus and mammary gland during the estrous cycle.
AB  - In rodents, progesterone receptors (PRs) A and B have different and often
      nonoverlapping roles, and this study asked whether different activities of the PR
      proteins in mouse are related to differences in their expression in reproductive
      tissues. The individual expression of PRA and PRB was determined
      immunohistochemically in mammary gland and uterus during the estrous cycle or in
      response to endocrine manipulation. In the mammary gland, PRA and PRB were
      colocated in PR+ epithelial cells, with little change during the estrous cycle.
      In the uterus, PRA was not detected in luminal epithelium at any stage of the
      cycle, and PR+ luminal cells expressed only PRB. In the stroma and myometrium,
      PRA and PRB levels fluctuated with cyclical systemic hormone exposure.
      Observation of functional end points suggested that augmented stromal and/or
      myometrial PRA in proestrus inhibited estrogen receptor expression and epithelial
      proliferation. Colocation of PRA and PRB was hormonally regulated, and
      ovariectomy did not reproduce the expression of PRA and PRB in the uterus during
      the estrous cycle. Whereas PRB was the only PR in the luminal epithelium in
      cycling mice, ovariectomy restored PRA expression, resulting in PRA-PRB
      colocation. In stroma and myometrium, PRA and PRB colocated in PR+ cells, but
      ovariectomy reduced PRA levels more than PRB, resulting in PRB-only-expressing
      cells. This study has shown that nonoverlapping PRA and PRB expression in the
      uterus, in particular the lack of PRA, and expression of PRB only in the luminal
      epithelium throughout the estrous cycle, is likely to contribute to the distinct
      roles of PRA and PRB in the adult mouse.

PMID- 16980439
TI  - Single-minded view of melanocortin signaling in energy homeostasis.

PMID- 16980440
TI  - The energy request of inflammation.

PMID- 16980441
TI  - Targeting B cells in Graves' disease.

PMID- 16980443
TI  - Mutants, suppressors, and wrinkled colonies: mutant alleles of the cell division
      gene ftsQ point to functional domains in FtsQ and a role for domain 1C of FtsA in
      divisome assembly.
AB  - Cell division in Escherichia coli requires the concerted action of at least 10
      essential proteins. One of these proteins, FtsQ, is physically associated with
      multiple essential division proteins, including FtsK, FtsL, FtsB, FtsW, and FtsI.
      In this work we performed a genetic analysis of the ftsQ gene. Our studies
      identified C-terminal residues essential for FtsQ's interaction with two
      downstream proteins, FtsL and FtsB. Here we also describe a novel screen for cell
      division mutants based on a wrinkled-colony morphology, which yielded several new
      point mutations in ftsQ. Two of these mutations affect localization of FtsQ to
      midcell and together define a targeting role for FtsQ's alpha domain. Further
      characterization of one localization-defective mutant protein [FtsQ(V92D)]
      revealed an unexpected role in localization for the first 49 amino acids of FtsQ.
      Finally, we found a suppressor of FtsQ(V92D) that was due to a point mutation in
      domain 1C of FtsA, a domain previously implicated in the recruitment of divisome
      proteins. However, despite reports of a potential interaction between FtsA and
      FtsQ, suppression by FtsA(I143L) is not mediated via direct contact with FtsQ.
      Rather, this mutation acts as a general suppressor of division defects, which
      include deletions of the normally essential genes zipA and ftsK and mutations in
      FtsQ that affect both localization and recruitment. Together, these results
      reveal increasingly complex connections within the bacterial divisome.

PMID- 16980444
TI  - The Escherichia coli rpoS-dependent htrC gene is not involved in the heat shock
      response.
AB  - We found that a new mutant with a deletion/replacement of the Escherichia coli K
      12 htrC gene, a gene previously reported to be required for growth at elevated
      temperatures, is not temperature sensitive. Furthermore, the original mutants,
      kindly provided by the original authors, although temperature sensitive, do not
      have mutations in the open reading frame designated htrC. We found that htrC
      requires RpoS for enhanced expression in the early stationary phase and is
      expressed at very low levels until then. The growth of our htrC mutant slowed
      during the early stationary phase, and the mutant was replaced by its parent in
      mixed cultures. Since we cannot assign a function or distinctive phenotype to
      htrC, we suggest that this open reading frame should be given a positional
      designation, yjaZ, until a specific function is identified.

PMID- 16980445
TI  - GroES/GroEL and DnaK/DnaJ have distinct roles in stress responses and during cell
      cycle progression in Caulobacter crescentus.
AB  - Misfolding and aggregation of protein molecules are major threats to all living
      organisms. Therefore, cells have evolved quality control systems for proteins
      consisting of molecular chaperones and proteases, which prevent protein
      aggregation by either refolding or degrading misfolded proteins. DnaK/DnaJ and
      GroES/GroEL are the best-characterized molecular chaperone systems in bacteria.
      In Caulobacter crescentus these chaperone machines are the products of essential
      genes, which are both induced by heat shock and cell cycle regulated. In this
      work, we characterized the viabilities of conditional dnaKJ and groESL mutants
      under different types of environmental stress, as well as under normal
      physiological conditions. We observed that C. crescentus cells with GroES/EL
      depleted are quite resistant to heat shock, ethanol, and freezing but are
      sensitive to oxidative, saline, and osmotic stresses. In contrast, cells with
      DnaK/J depleted are not affected by the presence of high concentrations of
      hydrogen peroxide, NaCl, and sucrose but have a lower survival rate after heat
      shock, exposure to ethanol, and freezing and are unable to acquire
      thermotolerance. Cells lacking these chaperones also have morphological defects
      under normal growth conditions. The absence of GroE proteins results in long,
      pinched filamentous cells with several Z-rings, whereas cells lacking DnaK/J are
      only somewhat more elongated than normal predivisional cells, and most of them do
      not have Z-rings. These findings indicate that there is cell division arrest,
      which occurs at different stages depending on the chaperone machine affected.
      Thus, the two chaperone systems have distinct roles in stress responses and
      during cell cycle progression in C. crescentus.

PMID- 16980446
TI  - pH-dependent activation of the BarA-UvrY two-component system in Escherichia
      coli.
AB  - The barA and uvrY genes of Escherichia coli encode a two-component sensor kinase
      and a response regulator, respectively. Although this system plays a major role
      in the regulation of central carbon metabolism, motility, and biofilm formation
      by controlling the expression of the CsrB and CsrC noncoding RNAs, the
      environmental conditions and the physiological signal(s) to which it responds
      remain obscure. In this study, we explored the effect of external pH on the
      activity of BarA/UvrY. Our results indicate that a pH lower than 5.5 provides an
      environment that does not allow activation of the BarA/UvrY signaling pathway.

PMID- 16980447
TI  - Role of DNA polymerase IV in Escherichia coli SOS mutator activity.
AB  - Constitutive expression of the SOS regulon in Escherichia coli recA730 strains
      leads to a mutator phenotype (SOS mutator) that is dependent on DNA polymerase V
      (umuDC gene product). Here we show that a significant fraction of this effect
      also requires DNA polymerase IV (dinB gene product).

PMID- 16980448
TI  - Revised model for Enterococcus faecalis fsr quorum-sensing system: the small open
      reading frame fsrD encodes the gelatinase biosynthesis-activating pheromone
      propeptide corresponding to staphylococcal agrd.
AB  - Gelatinase biosynthesis-activating pheromone (GBAP) is an autoinducing peptide
      involved in Enterococcus faecalis fsr quorum sensing, and its 11-amino-acid
      sequence has been identified in the C-terminal region of the 242-residue deduced
      fsrB product (J. Nakayama et al., Mol. Microbiol. 41:145-154, 2001). In this
      study, however, we demonstrated the existence of fsrD, encoding the GBAP
      propeptide, which is in frame with fsrB but is translated independently of fsrB.
      It was also demonstrated that FsrB', an FsrD segment-truncated FsrB, functions as
      a cysteine protease-like processing enzyme to generate GBAP from FsrD. This
      revised model is consistent with the staphylococcal agr system.

PMID- 16980449
TI  - Mechanisms of transcription activation exerted by GadX and GadW at the gadA and
      gadBC gene promoters of the glutamate-based acid resistance system in Escherichia
      coli.
AB  - In Escherichia coli the gad system protects the cell from the extreme acid stress
      encountered during transit through the host stomach. The structural genes gadA,
      gadB, and gadC encode two glutamate decarboxylase isoforms and a glutamate/gamma
      aminobutyrate (GABA) antiporter, respectively. Glutamate decarboxylation involves
      both proton consumption and production of GABA, a neutral compound which is
      finally exported via the GadC antiporter. Regulation of gadA and gadBC
      transcription is very complex, involving several circuits controlling expression
      under different growth phase, medium, and pH conditions. In this study we found
      that the AraC-like activators GadX and GadW share the same 44-bp binding sites in
      the gadA and gadBC regulatory regions. The common binding sites are centered at
      110.5 bp and 220.5 bp upstream of the transcriptional start points of the gadA
      and gadBC genes, respectively. At the gadA promoter this regulatory element
      overlaps one of the binding sites of the repressor H-NS. The DNA of the gadBC
      promoter has an intrinsic bend which is centered at position -121. These
      findings, combined with transcriptional regulation studies, may account for the
      two different mechanisms of transcriptional activation by GadX and GadW at the
      two promoters studied. We speculate that while at the gadA promoter GadX and GadW
      activate transcription by displacing H-NS via an antirepressor mechanism, at the
      gadBC promoter the mechanism of activation involves looping of the DNA sequence
      between the promoter and the activator binding site.

PMID- 16980450
TI  - Control of EpsE, the phosphoglycosyltransferase initiating exopolysaccharide
      synthesis in Streptococcus thermophilus, by EpsD tyrosine kinase.
AB  - We studied the roles of Streptococcus thermophilus phosphogalactosyltransferase
      (EpsE) (the priming enzyme), tyrosine kinase (EpsD), phosphatase (EpsB), and a
      membrane-associated protein with no known biochemical function (EpsC) in
      exopolysaccharide (EPS) synthesis. These proteins are well-conserved among
      bacteria and are usually encoded by clustered genes. Exopolysaccharide synthesis
      took place in the wild-type strain and a mutant lacking EpsB but not in mutants
      lacking EpsC, EpsD, or EpsE. The three mutants unable to synthesize EPS lacked
      the EpsE phosphogalactosyltransferase activity, while the two EPS-synthesizing
      strains possessed this activity, showing that EpsC and EpsD are required for EpsE
      function. An EpsD phosphorylated form was found in all strains except the epsC
      mutant, indicating that EpsC is necessary for EpsD phosphorylation. Moreover, the
      phosphorylated form of EpsD, a supposedly cytoplasmic protein, was found to be
      associated with the plasma membrane, possibly due to interaction with EpsC.
      Finally, the EpsD and EpsE elution profiles in a gel filtration chromatography
      assay were similar, suggesting that these two proteins colocalize in the
      membrane. Mutation of Tyr200, predicted to be a phosphorylation site and present
      in a conserved motif in bacterial phosphoglycosyltransferases, led to EpsE
      inactivation. In contrast, mutation of Tyr162 or Tyr199 had no effect. Taken
      together, these data show that EpsD controls EpsE activity. Possible mechanisms
      for this control are discussed.

PMID- 16980451
TI  - Heme utilization in Campylobacter jejuni.
AB  - A putative iron- and Fur-regulated hemin uptake gene cluster, composed of the
      transport genes chuABCD and a putative heme oxygenase gene (Cj1613c), has been
      identified in Campylobacter jejuni NCTC 11168. Mutation of chuA or Cj1613c leads
      to an inability to grow in the presence of hemin or hemoglobin as a sole source
      of iron. Mutation of chuB, -C, or -D only partially attenuates growth where hemin
      is the sole iron source, suggesting that an additional inner membrane (IM) ABC
      (ATP-binding cassette) transport system(s) for heme is present in C. jejuni.
      Genotyping experiments revealed that Cj1613c is highly conserved in 32 clinical
      isolates. One strain did not possess chuC, though it was still capable of using
      hemin/hemoglobin as a sole iron source, supporting the hypothesis that additional
      IM transport genes are present. In two other strains, sequence variations within
      the gene cluster were apparent and may account for an observed negative heme
      utilization phenotype. Analysis of promoter activity within the Cj1613c-chuA
      intergenic spacer region revealed chuABCD and Cj1613c are expressed from separate
      iron-repressed promoters and that this region also specifically binds purified
      recombinant Fur(Cj) in gel retardation studies. Absorbance spectroscopy of
      purified recombinant His(6)-Cj1613c revealed a 1:1 heme:His(6)-Cj1613c binding
      ratio. The complex was oxidatively degraded in the presence of ascorbic acid as
      the electron donor, indicating that the Cj1613c gene product functions as a heme
      oxygenase. In conclusion, we confirm the involvement of Cj1613c and ChuABCD in
      heme/hemoglobin utilization in C. jejuni.

PMID- 16980452
TI  - Analysis of Pseudomonas aeruginosa conditional psl variants reveals roles for the
      psl polysaccharide in adhesion and maintaining biofilm structure postattachment.
AB  - The ability to form biofilms in the airways of people suffering from cystic
      fibrosis is a critical element of Pseudomonas aeruginosa pathogenesis. The 15
      gene psl operon encodes a putative polysaccharide that plays an important role in
      biofilm initiation in nonmucoid P. aeruginosa strains. Biofilm initiation by a P.
      aeruginosa PAO1 strain with disruption of pslA and pslB (DeltapslAB) was severely
      compromised, indicating that psl has a role in cell-surface interactions. In this
      study, we investigated the adherence properties of this DeltapslAB mutant using
      biotic surfaces (epithelial cells and mucin-coated surfaces) and abiotic
      surfaces. Our results showed that psl is required for attachment to a variety of
      surfaces, independent of the carbon source. To study the potential roles of Psl
      apart from attachment, we generated a psl-inducible P. aeruginosa strain
      (Deltapsl/p(BAD)-psl) by replacing the psl promoter region with araC-p(BAD), so
      that expression of psl could be controlled by addition of arabinose. Analysis of
      biofilms formed by the Deltapsl/p(BAD)-psl strain indicated that expression of
      the psl operon is required to maintain the biofilm structure at steps
      postattachment. Overproduction of the Psl polysaccharide led to enhanced cell
      surface and intercellular adhesion of P. aeruginosa. This translated into
      significant changes in the architecture of the biofilm. We propose that Psl has
      an important role in P. aeruginosa adhesion, which is critical for initiation and
      maintenance of the biofilm structure.

PMID- 16980453
TI  - Initiation of heat-induced replication requires DnaA and the L-13-mer of oriC.
AB  - An upshift of 10 degrees C or more in the growth temperature of an Escherichia
      coli culture causes induction of extra rounds of chromosome replication. This
      stress replication initiates at oriC but has functional requirements different
      from those of cyclic replication. We named this phenomenon heat-induced
      replication (HIR). Analysis of HIR in bacterial strains that had complete or
      partial oriC deletions and were suppressed by F integration showed that no
      sequence outside oriC is used for HIR. Analysis of a number of oriC mutants
      showed that deletion of the L-13-mer, which makes oriC inactive for cyclic
      replication, was the only mutation studied that inactivated HIR. The requirement
      for this sequence was strictly correlated with Benham's theoretical stress
      induced DNA duplex destabilization. oriC mutations at DnaA, FIS, or IHF binding
      sites showed normal HIR activation, but DnaA was required for HIR. We suggest
      that strand opening for HIR initiation occurs due to heat-induced destabilization
      of the L-13-mer, and the stable oligomeric DnaA-single-stranded oriC complex
      might be required only to load the replicative helicase DnaB.

PMID- 16980454
TI  - Genome-wide analysis of light sensing in Prochlorococcus.
AB  - Prochlorococcus MED4 has, with a total of only 1,716 annotated protein-coding
      genes, the most compact genome of a free-living photoautotroph. Although light
      quality and quantity play an important role in regulating the growth rate of this
      organism in its natural habitat, the majority of known light-sensing proteins are
      absent from its genome. To explore the potential for light sensing in this
      phototroph, we measured its global gene expression pattern in response to
      different light qualities and quantities by using high-density Affymetrix
      microarrays. Though seven different conditions were tested, only blue light
      elicited a strong response. In addition, hierarchical clustering revealed that
      the responses to high white light and blue light were very similar and different
      from that of the lower-intensity white light, suggesting that the actual sensing
      of high light is mediated via a blue-light receptor. Bacterial cryptochromes seem
      to be good candidates for the blue-light sensors. The existence of a signaling
      pathway for the redox state of the photosynthetic electron transport chain was
      suggested by the presence of genes that responded similarly to red and blue light
      as well as genes that responded to the addition of DCMU [3-(3,4-dichlorophenyl)
      1,1-N-N'-dimethylurea], a specific inhibitor of photosystem II-mediated electron
      transport.

PMID- 16980455
TI  - Species-specific differences in the activity of PrfA, the key regulator of
      listerial virulence genes.
AB  - PrfA, the master regulator of LIPI-1, is indispensable for the pathogenesis of
      the human pathogen Listeria monocytogenes and the animal pathogen Listeria
      ivanovii. PrfA is also present in the apathogenic species Listeria seeligeri, and
      in this study, we elucidate the differences between PrfA proteins from the
      pathogenic and apathogenic species of the genus Listeria. PrfA proteins of L.
      monocytogenes (PrfA(Lm) and PrfA*(Lm)), L. ivanovii (PrfA(Li)), and L. seeligeri
      (PrfA(Ls)) were purified, and their equilibrium constants for binding to the PrfA
      box of the hly promoter (Phly(Lm)) were determined by surface plasmon resonance.
      In addition, the capacities of these PrfA proteins to bind to the PrfA-dependent
      promoters Phly and PactA and to form ternary complexes together with RNA
      polymerase were analyzed in electrophoretic mobility shift assays, and their
      abilities to initiate transcription in vitro starting at these promoters were
      compared. The results show that PrfA(Li) resembled the constitutively active
      mutant PrfA*(Lm) more than the wild-type PrfA(Lm), whereas PrfA(Ls) showed a
      drastically reduced capacity to bind to the PrfA-dependent promoters Phly and
      PactA. In contrast, the efficiencies of PrfA(Lm), PrfA*(Lm), and PrfA(Li) forming
      ternary complexes and initiating transcription at Phly and PactA were rather
      similar, while those of PrfA(Ls) were also much lower. The low binding and
      transcriptional activation capacities of PrfA(Ls) seem to be in part due to amino
      acid exchanges in its C-terminal domain (compared to PrfA(Lm) and PrfA(Li)). In
      contrast to the significant differences in the biochemical properties of
      PrfA(Lm), PrfA(Li), and PrfA(Ls), the PrfA-dependent promoters of hly (Phly(Lm),
      Phly(L)(i), and Phly(L)(s)) and actA (PactA(Lm), PactA(L)(i), and PactA(L)(s)) of
      the three Listeria species did not significantly differ in their binding
      affinities to the various PrfA proteins and in their strengths to promote
      transcription in vitro. The allelic replacement of prfA(Lm) with prfA(Ls) in L.
      monocytogenes leads to low expression of PrfA-dependent genes and to reduced in
      vivo virulence of L. monocytogenes, suggesting that the altered properties of
      PrfA(Ls) protein are a major cause for the low virulence of L. seeligeri.

PMID- 16980457
TI  - Conservation and variation between Rhodobacter capsulatus and Escherichia coli
      Tat systems.
AB  - The Tat system allows the translocation of folded and often cofactor-containing
      proteins across biological membranes. Here, we show by an interspecies transfer
      of a complete Tat translocon that Tat systems are largely, but not fully,
      interchangeable even between different classes of proteobacteria. The Tat
      apparatus from the alpha-proteobacterium Rhodobacter capsulatus was transferred
      to a Tat-deficient Escherichia coli strain, which is a gamma-proteobacterium.
      Similar to that of E. coli, the R. capsulatus Tat system consists of three
      components, rc-TatA, rc-TatB, and rc-TatC. A fourth gene (rc-tatF) is present in
      the rc-tatABCF operon which has no apparent relevance for translocation. The
      translational starts of rc-tatC and rc-tatF overlap in four nucleotides (ATGA)
      with the preceding tat genes, pointing to efficient translational coupling of rc
      tatB, rc-tatC, and rc-tatF. We show by a variety of physiological and biochemical
      assays that the R. capsulatus Tat system functionally targets the E. coli Tat
      substrates TorA, AmiA, AmiC, and formate dehydrogenase. Even a Tat substrate from
      a third organism is accepted, demonstrating that usually Tat systems and Tat
      substrates from different proteobacteria are compatible with each other. Only one
      exceptional Tat substrate of E. coli, a membrane-anchored dimethyl sulfoxide
      (DMSO) reductase, was not targeted by the R. capsulatus Tat system, resulting in
      a DMSO respiration deficiency. Although the general features of Tat substrates
      and translocons are similar between species, the data indicate that details in
      the targeting pathways can vary considerably.

PMID- 16980456
TI  - Genome sequence of Aeromonas hydrophila ATCC 7966T: jack of all trades.
AB  - The complete genome of Aeromonas hydrophila ATCC 7966(T) was sequenced.
      Aeromonas, a ubiquitous waterborne bacterium, has been placed by the
      Environmental Protection Agency on the Contaminant Candidate List because of its
      potential to cause human disease. The 4.7-Mb genome of this emerging pathogen
      shows a physiologically adroit organism with broad metabolic capabilities and
      considerable virulence potential. A large array of virulence genes, including
      some identified in clinical isolates of Aeromonas spp. or Vibrio spp., may confer
      upon this organism the ability to infect a wide range of hosts. However, two
      recognized virulence markers, a type III secretion system and a lateral
      flagellum, that are reported in other A. hydrophila strains are not identified in
      the sequenced isolate, ATCC 7966(T). Given the ubiquity and free-living lifestyle
      of this organism, there is relatively little evidence of fluidity in terms of
      mobile elements in the genome of this particular strain. Notable aspects of the
      metabolic repertoire of A. hydrophila include dissimilatory sulfate reduction and
      resistance mechanisms (such as thiopurine reductase, arsenate reductase, and
      phosphonate degradation enzymes) against toxic compounds encountered in polluted
      waters. These enzymes may have bioremediative as well as industrial potential.
      Thus, the A. hydrophila genome sequence provides valuable insights into its
      ability to flourish in both aquatic and host environments.

PMID- 16980458
TI  - Pirin regulates pyruvate catabolism by interacting with the pyruvate
      dehydrogenase E1 subunit and modulating pyruvate dehydrogenase activity.
AB  - The protein pirin, which is involved in a variety of biological processes, is
      conserved from prokaryotic microorganisms, fungi, and plants to mammals. It acts
      as a transcriptional cofactor or an apoptosis-related protein in mammals and is
      involved in seed germination and seedling development in plants. In prokaryotes,
      while pirin is stress induced in cyanobacteria and may act as a quercetinase in
      Escherichia coli, the functions of pirin orthologs remain mostly uncharacterized.
      We show that the Serratia marcescens pirin (pirin(Sm)) gene encodes an ortholog
      of pirin protein. Protein pull-down and bacterial two-hybrid assays followed by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrospray
      ionization-tandem mass spectrometry analyses showed the pyruvate dehydrogenase
      (PDH) E1 subunit as a component interacting with the pirin(Sm) gene. Functional
      analyses showed that both PDH E1 subunit activity and PDH enzyme complex activity
      are inhibited by the pirin(Sm) gene in S. marcescens CH-1. The S. marcescens CH-1
      pirin(Sm) gene was subsequently mutated by insertion-deletion homologous
      recombination. Accordingly, the PDH E1 and PDH enzyme complex activities and
      cellular ATP concentration increased up to 250%, 140%, and 220%, respectively, in
      the S. marcescens CH-1 pirin(Sm) mutant. Concomitantly, the cellular NADH/NAD(+)
      ratio increased in the pirin(Sm) mutant, indicating increased tricarboxylic acid
      (TCA) cycle activity. Our results show that the pirin(Sm) gene plays a regulatory
      role in the process of pyruvate catabolism to acetyl coenzyme A through
      interaction with the PDH E1 subunit and inhibiting PDH enzyme complex activity in
      S. marcescens CH-1, and they suggest that pirin(Sm) is an important protein
      involved in determining the direction of pyruvate metabolism towards either the
      TCA cycle or the fermentation pathways.

PMID- 16980459
TI  - Structural investigations of the membrane-embedded rotor ring of the F-ATPase
      from Clostridium paradoxum.
AB  - The Na(+)-translocating F-ATPase of the thermoalkaliphilic bacterium Clostridium
      paradoxum harbors an oligomeric ring of c subunits that resists dissociation by
      sodium dodecyl sulfate. The c ring has been isolated and crystallized in two
      dimensions. From electron microscopy of these c-ring crystals, a projection map
      was calculated to 7 A resolution. In the projection map, each c ring consists of
      two concentric, slightly staggered, packed rings, each composed of 11 densities
      representing the alpha-helices. On the basis of these results, it was determined
      that the F-ATPase from C. paradoxum contains an undecameric c ring.

PMID- 16980460
TI  - Diguanylate cyclases control magnesium-dependent motility of Vibrio fischeri.
AB  - Flagellar biogenesis and hence motility of Vibrio fischeri depends upon the
      presence of magnesium. In the absence of magnesium, cells contain few or no
      flagella and are poorly motile or nonmotile. To dissect the mechanism by which
      this regulation occurs, we screened transposon insertion mutants for those that
      could migrate through soft agar medium lacking added magnesium. We identified
      mutants with insertions in two distinct genes, VF0989 and VFA0959, which we
      termed mifA and mifB, respectively, for magnesium-dependent induction of
      flagellation. Each gene encodes a predicted membrane-associated protein with
      diguanylate cyclase activity. Consistent with that activity, introduction into V.
      fischeri of medium-copy plasmids carrying these genes inhibited motility.
      Furthermore, multicopy expression of mifA induced other phenotypes known to be
      correlated with diguanylate cyclase activity, including cellulose biosynthesis
      and biofilm formation. To directly test their function, we introduced the wild
      type genes on high-copy plasmids into Escherichia coli. We assayed for the
      production of cyclic di-GMP using two-dimensional thin-layer chromatography and
      found that strains carrying these plasmids produced a small but reproducible spot
      that migrated with an R(f) value consistent with cyclic di-GMP that was not
      produced by strains carrying the vector control. Disruptions of mifA or mifB
      increased flagellin levels, while multicopy expression decreased them.
      Semiquantitative reverse transcription-PCR experiments revealed no significant
      difference in the amount of flagellin transcripts produced in either the presence
      or absence of Mg(2+) by either vector control or mifA-overexpressing cells,
      indicating that the impact of magnesium and cyclic-di-GMP primarily acts
      following transcription. Finally, we present a model for the roles of magnesium
      and cyclic di-GMP in the control of motility of V. fischeri.

PMID- 16980461
TI  - Phosphorylation of phenol by phenylphosphate synthase: role of histidine
      phosphate in catalysis.
AB  - The anaerobic metabolism of phenol proceeds via carboxylation to 4
      hydroxybenzoate by a two-step process involving seven proteins and two enzymes
      ("biological Kolbe-Schmitt carboxylation"). MgATP-dependent phosphorylation of
      phenol catalyzed by phenylphosphate synthase is followed by phenylphosphate
      carboxylation. Phenylphosphate synthase shows similarities to phosphoenolpyruvate
      (PEP) synthase and was studied for the bacterium Thauera aromatica. It consists
      of three proteins and transfers the beta-phosphoryl from ATP to phenol; the
      products are phenylphosphate, AMP, and phosphate. We showed that protein 1
      becomes phosphorylated in the course of the reaction cycle by [beta-(32)P]ATP.
      This reaction requires protein 2 and is severalfold stimulated by protein 3.
      Stimulation of the reaction by 1 M sucrose is probably due to stabilization of
      the protein(s). Phosphorylated protein 1 transfers the phosphoryl group to
      phenolic substrates. The primary structure of protein 1 was analyzed by
      nanoelectrospray mass spectrometry after CNBr cleavage, trypsin digestion, and
      online high-pressure liquid chromatography at alkaline pH. His-569 was identified
      as the phosphorylated amino acid. We propose a catalytic ping-pong mechanism
      similar to that of PEP synthase. First, a diphosphoryl group is transferred to
      His-569 in protein 1, from which phosphate is cleaved to render the reaction
      unidirectional. Histidine phosphate subsequently serves as the actual
      phosphorylation agent.

PMID- 16980463
TI  - A novel gene involved in regulating the flagellar gene cascade in Proteus
      mirabilis.
AB  - In this study, we identified a transposon insertion in a novel gene, designated
      disA, that restored swarming motility to a putrescine-deficient speA mutant of
      Proteus mirabilis. A null allele in disA also increased swarming in a wild-type
      background. The DisA gene product was homologous to amino acid decarboxylases,
      and its role in regulating swarming was investigated by examining the expression
      of genes in the flagellar cascade. In a disA mutant background, we observed a 1.4
      fold increase in the expression of flhDC, which encodes FlhD(2)C(2), the master
      regulator of the flagellar gene cascade. However, the expressions of class 2
      (fliA, flgM) and class 3 (flaA) genes were at least 16-fold higher in the disA
      background during swarmer cell differentiation. Overexpression of DisA on a high
      copy-number plasmid did not significantly decrease flhDC mRNA accumulation but
      resulted in a complete block in mRNA accumulation for both fliA and flaA. DisA
      overexpression also blocked swarmer cell differentiation. The disA gene was
      regulated during the swarming cycle, and a single-copy disA::lacZ fusion
      exhibited a threefold increase in expression in swarmer cells. Given that DisA
      was similar to amino acid decarboxylases, a panel of decarboxylated amino acids
      was tested for effects similar to DisA overexpression, and phenethylamine, the
      product of phenylalanine decarboxylation, was capable of inhibiting both swarming
      and the expression of class 2 and class 3 genes in the flagellar regulon. A DisA
      dependent decarboxylated amino acid may inhibit the formation of active
      FlhD(2)C(2) heterotetramers or inhibit FlhD(2)C(2) binding to DNA.

PMID- 16980462
TI  - Reporter metabolite analysis of transcriptional profiles of a Staphylococcus
      aureus strain with normal phenotype and its isogenic hemB mutant displaying the
      small-colony-variant phenotype.
AB  - In this study, full-genome DNA microarrays based on the sequence of
      Staphylococcus aureus N315 were used to compare the transcriptome of a clinical
      S. aureus strain with a normal phenotype to that of its isogenic mutant with a
      stable small-colony-variant (SCV) phenotype (hemB::ermB). In addition to standard
      statistical analyses, systems biology advances were applied to identify reporter
      metabolites and to achieve a more detailed survey of genome-wide expression
      differences between the hemB mutant and its parental strain. Genes of enzymes
      involved in glycolytic and fermentative pathways were found to be up-regulated in
      the hemB mutant. Furthermore, our analyses allowed identification of additional
      differences between the normal-phenotype S. aureus and the SCV, most of which
      were related to metabolism. Profound differences were identified especially in
      purine biosynthesis as well as in arginine and proline metabolism. Of particular
      interest, a hypothetical gene of the Crp/Fnr family (SA2424) that is part of the
      arginine-deiminase (AD) pathway, whose homologue in Streptococcus suis is assumed
      to be involved in intracellular persistence, showed significantly increased
      transcription in the hemB mutant. The hemB mutant potentially uses the up
      regulated AD pathway to produce ATP or (through ammonia production) to counteract
      the acidic environment that prevails intracellularly. Moreover, genes involved in
      capsular polysaccharide and cell wall synthesis were found to be significantly up
      regulated in the hemB mutant and therefore potentially responsible for the
      changed cell morphology of SCVs. In conclusion, the identified differences may be
      responsible for the SCV phenotype and its association with chronic and persistent
      infections.

PMID- 16980464
TI  - Comparative and functional genomic analyses of iron transport and regulation in
      Leptospira spp.
AB  - The spirochetes of the Leptospira genus contain saprophytic and pathogenic
      members, the latter being responsible for leptospirosis. Despite the recent
      sequencing of the genome of the pathogen L. interrogans, the slow growth of these
      bacteria, their virulence in humans, and a lack of genetic tools make it
      difficult to work with these pathogens. In contrast, the development of numerous
      genetic tools for the saprophyte L. biflexa enables its use as a model bacterium.
      Leptospira spp. require iron for growth. In this work, we show that Leptospira
      spp. can acquire iron from different sources, including siderophores. A
      comparative genome analysis of iron uptake systems and their regulation in the
      saprophyte L. biflexa and the pathogen L. interrogans is presented in this study.
      Our data indicated that, for instance, L. biflexa and L. interrogans contain 8
      and 12 genes, respectively, whose products share homology with proteins that have
      been shown to be TonB-dependent receptors. We show that some genes involved in
      iron uptake were differentially expressed in response to iron. In addition, we
      were able to disrupt several putative genes involved in iron acquisition systems
      or iron regulation in L. biflexa. Comparative genomics, in combination with gene
      inactivation, gives us significant functional information on iron homeostasis in
      Leptospira spp.

PMID- 16980465
TI  - Transcription modulation of Salmonella enterica serovar Typhimurium promoters by
      sub-MIC levels of rifampin.
AB  - Promoter-lux fusions that showed rifampin-modulated transcription were identified
      from a Salmonella enterica serovar Typhimurium 14028 reporter library. The
      transformation of a subset of fusions into mutants that lacked one of six global
      regulatory proteins or were rifampin resistant showed that transcription
      modulation was independent of the global regulators, promoter specific, and
      dependent on the interaction of rifampin with RNA polymerase.

PMID- 16980466
TI  - The Methanosarcina barkeri genome: comparative analysis with Methanosarcina
      acetivorans and Methanosarcina mazei reveals extensive rearrangement within
      methanosarcinal genomes.
AB  - We report here a comparative analysis of the genome sequence of Methanosarcina
      barkeri with those of Methanosarcina acetivorans and Methanosarcina mazei. The
      genome of M. barkeri is distinguished by having an organization that is well
      conserved with respect to the other Methanosarcina spp. in the region proximal to
      the origin of replication, with interspecies gene similarities as high as 95%.
      However, it is disordered and marked by increased transposase frequency and
      decreased gene synteny and gene density in the distal semigenome. Of the 3,680
      open reading frames (ORFs) in M. barkeri, 746 had homologs with better than 80%
      identity to both M. acetivorans and M. mazei, while 128 nonhypothetical ORFs were
      unique (nonorthologous) among these species, including a complete formate
      dehydrogenase operon, genes required for N-acetylmuramic acid synthesis, a 14
      gene gas vesicle cluster, and a bacterial-like P450-specific ferredoxin reductase
      cluster not previously observed or characterized for this genus. A cryptic 36-kbp
      plasmid sequence that contains an orc1 gene flanked by a presumptive origin of
      replication consisting of 38 tandem repeats of a 143-nucleotide motif was
      detected in M. barkeri. Three-way comparison of these genomes reveals differing
      mechanisms for the accrual of changes. Elongation of the relatively large M.
      acetivorans genome is the result of uniformly distributed multiple gene scale
      insertions and duplications, while the M. barkeri genome is characterized by
      localized inversions associated with the loss of gene content. In contrast, the
      short M. mazei genome most closely approximates the putative ancestral
      organizational state of these species.

PMID- 16980467
TI  - plcR papR-independent expression of anthrolysin O by Bacillus anthracis.
AB  - Cholesterol-dependent cytolysins (CDCs) are secreted, pore-forming toxins that
      are associated with pathogenesis in a variety of gram-positive bacteria. Bacillus
      anthracis produces anthrolysin O (ALO), a CDC that is largely responsible for the
      hemolytic activity of culture supernates when the bacterium is cultured in
      appropriate conditions. B. cereus and B. thuringiensis, species closely related
      to B. anthracis, produce CDCs with significant amino acid sequence homology to
      ALO. Transcription of the B. cereus and B. thuringiensis CDC genes is controlled
      by PlcR, a transcription regulator that requires a pentapeptide derived from the
      papR gene product for binding to a consensus sequence (PlcR box) and
      transcriptional activation of downstream genes. A PlcR box precedes the B.
      anthracis alo gene, and the B. anthracis genome contains three plcR-like genes,
      one of which harbors a nonsense mutation that is predicted to result in a
      truncated, nonfunctional protein. We detected mRNA of alo, papR, and the three
      plcR-like genes in spleens of B. anthracis-infected mice, indicating gene
      expression in vivo. Analysis of alo transcription in batch culture revealed a
      potential transcription start located between the PlcR box and the translational
      start. Nevertheless, steady-state levels of alo transcripts and ALO protein were
      unaffected by deletion of papR or disruption of the PlcR box. Our data indicate
      that despite the presence of the transcriptionally active plcR and papR genes in
      B. anthracis and a PlcR box in the promoter region of the alo gene, alo
      expression is independent of this control system.

PMID- 16980468
TI  - Salmonella enterica serovar Typhimurium periplasmic superoxide dismutase SodCI is
      a member of the PhoPQ regulon and is induced in macrophages.
AB  - Salmonella enterica serovar Typhimurium replicates within host macrophages during
      the systemic stage of infection. In the macrophage, the bacteria must survive the
      respiratory burst that produces superoxide. Serovar Typhimurium strain 14028
      produces two periplasmic superoxide dismutases, SodCI and SodCII, but only SodCI
      contributes to virulence. Although we have shown that this is primarily due to
      differences in the two proteins, evidence suggests differential regulation of the
      two genes. Using transcriptional sodCI- and sodCII-lac fusions, we show that
      sodCII is under the control of the RpoS sigma factor, as was known for the
      Escherichia coli ortholog, sodC. In contrast, we show that sodCI is
      transcriptionally controlled by the PhoPQ two-component regulatory system, which
      regulates an array of virulence genes required for macrophage survival.
      Introduction of a phoP-null mutation into the sodCI fusion strain resulted in a
      decrease in transcription and loss of regulation. The sodCI-lac fusion showed
      high-level expression in a background containing a phoQ constitutive allele. The
      sodCI gene is induced 15-fold in bacteria recovered from either the tissue
      culture macrophages or the spleens of infected mice. Induction in macrophages is
      dependent on PhoP. The sodCII fusion was induced three- to fourfold in
      macrophages and animals; this induction was unaffected by loss of PhoP. Thus,
      sodCI, which is horizontally transferred by the Gifsy-2 phage, is regulated by
      PhoPQ such that it is induced at the appropriate time and place to combat
      phagocytic superoxide.

PMID- 16980469
TI  - Uncovering a large set of genes that affect surface motility in Salmonella
      enterica serovar Typhimurium.
AB  - We describe a large set of genes affecting motility in Salmonella enterica
      serovar Typhimurium. Identified in microarray experiments as displaying flagellar
      gene expression patterns or controlled by known flagellar regulators, we show
      that null mutations in these genes primarily affect swarming motility. Three
      genes function in chemotaxis.

PMID- 16980470
TI  - Mutation of His-157 in the second pore loop drastically reduces the activity of
      the Synechocystis Ktr-type transporter.
AB  - Mutation of a conserved His-157 in the second pore loop of KtrB drastically
      reduced the activity of the K+ transporter from Synechocystis sp. strain PCC
      6803. This result suggests that His-157 plays an essential role in the K+
      transport activity of the transporter system.

PMID- 16980471
TI  - ExsY and CotY are required for the correct assembly of the exosporium and spore
      coat of Bacillus cereus.
AB  - The exosporium-defective phenotype of a transposon insertion mutant of Bacillus
      cereus implicated ExsY, a homologue of B. subtilis cysteine-rich spore coat
      proteins CotY and CotZ, in assembly of an intact exosporium. Single and double
      mutants of B. cereus lacking ExsY and its paralogue, CotY, were constructed. The
      exsY mutant spores are not surrounded by an intact exosporium, though they often
      carry attached exosporium fragments. In contrast, the cotY mutant spores have an
      intact exosporium, although its overall shape is altered. The single mutants show
      altered, but different, spore coat properties. The exsY mutant spore coat is
      permeable to lysozyme, whereas the cotY mutant spores are less resistant to
      several organic solvents than is the case for the wild type. The exsY cotY double
      mutant spores lack exosporium and have very thin coats that are permeable to
      lysozyme and are sensitive to chloroform, toluene, and phenol. These spore coat
      as well as exosporium defects suggest that ExsY and CotY are important to correct
      formation of both the exosporium and the spore coat in B. cereus. Both ExsY and
      CotY proteins were detected in Western blots of purified wild-type exosporium, in
      complexes of high molecular weight, and as monomers. Both exsY and cotY genes are
      expressed at late stages of sporulation.

PMID- 16980472
TI  - Crl facilitates RNA polymerase holoenzyme formation.
AB  - The Escherichia coli Crl protein has been described as a transcriptional
      coactivator for the stationary-phase sigma factor sigma(S). In a transcription
      system with highly purified components, we demonstrate that Crl affects
      transcription not only by the Esigma(S) RNA polymerase holoenzyme but also by
      Esigma(70) and Esigma(32). Crl increased transcription dramatically but only when
      the sigma concentration was low and when Crl was added to sigma prior to assembly
      with the core enzyme. Our results suggest that Crl facilitates holoenzyme
      formation, the first positive regulator identified with this mechanism of action.

PMID- 16980473
TI  - The Ser/Thr protein kinase PknB is essential for sustaining mycobacterial growth.
AB  - The receptor-like protein kinase PknB from Mycobacterium tuberculosis is encoded
      by the distal gene in a highly conserved operon, present in all actinobacteria,
      that may control cell shape and cell division. Genes coding for a PknB-like
      protein kinase are also found in many more distantly related gram-positive
      bacteria. Here, we report that the pknB gene can be disrupted by allelic
      replacement in M. tuberculosis and the saprophyte Mycobacterium smegmatis only in
      the presence of a second functional copy of the gene. We also demonstrate that
      eukaryotic Ser/Thr protein kinase inhibitors, which inactivate PknB in vitro with
      a 50% inhibitory concentration in the submicromolar range, are able to kill M.
      tuberculosis H37Rv, M. smegmatis mc(2)155, and Mycobacterium aurum A+ with MICs
      in the micromolar range. Furthermore, significantly higher concentrations of
      these compounds are required to inhibit growth of M. smegmatis strains
      overexpressing PknB, suggesting that this protein kinase is the molecular target.
      These findings demonstrate that the Ser/Thr protein kinase PknB is essential for
      sustaining mycobacterial growth and support the development of protein kinase
      inhibitors as new potential antituberculosis drugs.

PMID- 16980474
TI  - NAD+ utilization in Pasteurellaceae: simplification of a complex pathway.

PMID- 16980475
TI  - Differential dependence of StpA on H-NS in autoregulation of stpA and in
      regulation of bgl.
AB  - StpA has functional similarity to its homologue, the nucleoid structuring protein
      H-NS. It binds to AT-rich, planar, bent DNA and constrains DNA supercoils. In
      addition, StpA acts as an RNA chaperone. StpA and H-NS also form heterodimers.
      However, cellular levels of StpA are low due to repression of stpA by H-NS and
      negative autoregulation. Here we show that effective (30-fold) repression of stpA
      transcription requires a downstream regulator element located within the stpA
      coding region. In addition, we show that StpA represses stpA threefold in an hns
      null mutant. In contrast, repression of the bgl operon, another H-NS-repressed
      system, is not achieved by StpA alone. It becomes StpA dependent in the presence
      of a fusion protein encompassing the N-terminal 37 amino acids of H-NS, which
      comprise the core of the dimerization domain. StpA also effectively complements H
      NS-I119T, a mutant defective in specific DNA binding, in repression of the bgl
      operon. Thus, StpA complements H-NS proteins defective in DNA binding to repress
      bgl, while in autoregulation of stpA it acts autonomously, indicating a
      difference in the mechanisms of repression.

PMID- 16980476
TI  - Characterization of the Staphylococcus aureus heat shock, cold shock, stringent,
      and SOS responses and their effects on log-phase mRNA turnover.
AB  - Despite its being a leading cause of nosocomal and community-acquired infections,
      surprisingly little is known about Staphylococcus aureus stress responses. In the
      current study, Affymetrix S. aureus GeneChips were used to define transcriptome
      changes in response to cold shock, heat shock, stringent, and SOS response
      inducing conditions. Additionally, the RNA turnover properties of each response
      were measured. Each stress response induced distinct biological processes,
      subsets of virulence factors, and antibiotic determinants. The results were
      validated by real-time PCR and stress-mediated changes in antimicrobial agent
      susceptibility. Collectively, many S. aureus stress-responsive functions are
      conserved across bacteria, whereas others are unique to the organism. Sets of
      small stable RNA molecules with no open reading frames were also components of
      each response. Induction of the stringent, cold shock, and heat shock responses
      dramatically stabilized most mRNA species. Correlations between mRNA turnover
      properties and transcript titers suggest that S. aureus stress response-dependent
      alterations in transcript abundances can, in part, be attributed to alterations
      in RNA stability. This phenomenon was not observed within SOS-responsive cells.

PMID- 16980477
TI  - The Escherichia coli GTPase CgtAE is involved in late steps of large ribosome
      assembly.
AB  - The bacterial ribosome is an extremely complicated macromolecular complex the in
      vivo biogenesis of which is poorly understood. Although several bona fide
      assembly factors have been identified, their precise functions and temporal
      relationships are not clearly defined. Here we describe the involvement of an
      Escherichia coli GTPase, CgtA(E), in late steps of large ribosomal subunit
      biogenesis. CgtA(E) belongs to the Obg/CgtA GTPase subfamily, whose highly
      conserved members are predominantly involved in ribosome function. Mutations in
      CgtA(E) cause both polysome and rRNA processing defects; small- and large-subunit
      precursor rRNAs accumulate in a cgtA(E) mutant. In this study we apply a new
      semiquantitative proteomic approach to show that CgtA(E) is required for optimal
      incorporation of certain late-assembly ribosomal proteins into the large
      ribosomal subunit. Moreover, we demonstrate the interaction with the 50S
      ribosomal subunits of specific nonribosomal proteins (including heretofore
      uncharacterized proteins) and define possible temporal relationships between
      these proteins and CgtA(E). We also show that purified CgtA(E) associates with
      purified ribosomal particles in the GTP-bound form. Finally, CgtA(E)
      cofractionates with the mature 50S but not with intermediate particles
      accumulated in other large ribosome assembly mutants.

PMID- 16980478
TI  - A recA null mutation may be generated in Streptomyces coelicolor.
AB  - The recombinase RecA plays a crucial role in homologous recombination and the SOS
      response in bacteria. Although recA mutants usually are defective in homologous
      recombination and grow poorly, they nevertheless can be isolated in almost all
      bacteria. Previously, considerable difficulties were experienced by several
      laboratories in generating recA null mutations in Streptomyces, and the only recA
      null mutants isolated (from Streptomyces lividans) appeared to be accompanied by
      a suppressing mutation. Using gene replacement mediated by Escherichia coli
      Streptomyces conjugation, we generated recA null mutations in a series of
      Streptomyces coelicolor A3(2) strains. These recA mutants were very sensitive to
      mitomycin C but only moderately sensitive to UV irradiation, and the UV survival
      curves showed wide shoulders, reflecting the presence of a recA-independent
      repair pathway. The mutants segregated minute colonies with low viability during
      growth and produced more anucleate spores than the wild type. Some crosses
      between pairs of recA null mutants generated no detectable recombinants, showing
      for the first time that conjugal recombination in S. coelicolor is recA mediated,
      but other mutants retained the ability to undergo recombination. The nature of
      this novel recombination activity is unknown.

PMID- 16980479
TI  - Loss of expression of cspC, a cold shock family gene, confers a gain of fitness
      in Escherichia coli K-12 strains.
AB  - The CspA family of cold shock genes in Escherichia coli K-12 includes nine
      paralogs, cspA to cspI. Some of them have been implicated in cold stress
      adaptation. Screening for mutations among common laboratory E. coli strains
      showed a high degree of genetic diversity in cspC but not in cspA and cspE. This
      diversity in cspC was due to a wide spectrum of variations including insertions
      of IS elements, deletion, and point mutation. Northern analysis of these mutants
      showed loss of cspC expression in all but one case. Further analysis of the loss
      of-function cspC mutants showed that they have a fitness advantage in broth
      culture after 24 h over their isogenic wild-type derivatives. Conversely,
      introduction of mutated cspC alleles conferred a competitive fitness advantage to
      AB1157, a commonly used laboratory strain. This provides the evidence that loss
      of cspC expression is both necessary and sufficient to confer a gain of fitness
      as seen in broth culture over 24 h. Together, these results ascribe a novel role
      in cellular growth at 37 degrees C for CspC, a member of the cold shock domain
      containing protein family.

PMID- 16980480
TI  - PurF-independent phosphoribosyl amine formation in yjgF mutants of Salmonella
      enterica utilizes the tryptophan biosynthetic enzyme complex anthranilate
      synthase-phosphoribosyltransferase.
AB  - In Salmonella enterica, the biosynthetic pathways for the generation of purines
      and the essential cofactor thiamine pyrophosphate branch after sharing five
      enzymatic steps. Phosphoribosyl amine (PRA) is the first intermediate in the
      common portion of the pathway and is generated from phosphoribosylpyrophosphate
      and glutamine by the PurF enzyme (phosphoribosylpyrophosphate amidotransferase).
      A null mutation in yjgF allows PurF-independent PRA formation by an unknown
      mechanism. The tryptophan biosynthetic enzyme complex anthranilate synthase
      phosphoribosyltransferase, composed of the TrpD and TrpE proteins, was shown to
      be essential for PRA formation in strains lacking both yjgF and purF. The
      activity generating PRA in a yjgF mutant background has features that distinguish
      it from the TrpDE-mediated PRA formation shown previously for this enzyme in
      strains with an active copy of yjgF. The data presented here are consistent with
      a model in which the absence of YjgF uncovers a new catalytic activity of TrpDE.

PMID- 16980481
TI  - Molecular and population analyses of a recombination event in the catabolic
      plasmid pJP4.
AB  - Cupriavidus necator JMP134(pJP4) harbors a catabolic plasmid, pJP4, which confers
      the ability to grow on chloroaromatic compounds. Repeated growth on 3
      chlorobenzoate (3-CB) results in selection of a recombinant strain, which
      degrades 3-CB better but no longer grows on 2,4-dichlorophenoxyacetate (2,4-D).
      We have previously proposed that this phenotype is due to a double homologous
      recombination event between inverted repeats of the multicopies of this plasmid
      within the cell. One recombinant form of this plasmid (pJP4-F3) explains this
      phenotype, since it harbors two copies of the chlorocatechol degradation tfd gene
      clusters, which are essential to grow on 3-CB, but has lost the tfdA gene,
      encoding the first step in degradation of 2,4-D. The other recombinant plasmid
      (pJP4-FM) should harbor two copies of the tfdA gene but no copies of the tfd gene
      clusters. A molecular analysis using a multiplex PCR approach to distinguish the
      wild-type plasmid pJP4 from its two recombinant forms, was carried out. Expected
      PCR products confirming this recombination model were found and sequenced. Few
      recombinant plasmid forms in cultures grown in several carbon sources were
      detected. Kinetic studies indicated that cells containing the recombinant plasmid
      pJP4-FM were not selectable by sole carbon source growth pressure, whereas those
      cells harboring recombinant plasmid pJP4-F3 were selected upon growth on 3-CB.
      After 12 days of repeated growth on 3-CB, the complete plasmid population in C.
      necator JMP134 apparently corresponds to this form. However, wild-type plasmid
      forms could be recovered after growing this culture on 2,4-D, indicating that
      different plasmid forms can be found in C. necator JMP134 at the population
      level.

PMID- 16980482
TI  - Colocation of genes encoding a tRNA-mRNA hybrid and a putative signaling peptide
      on complementary strands in the genome of the hyperthermophilic bacterium
      Thermotoga maritima.
AB  - In the genome of the hyperthermophilic bacterium Thermotoga maritima, TM0504
      encodes a putative signaling peptide implicated in population density-dependent
      exopolysaccharide formation. Although not noted in the original genome
      annotation, TM0504 was found to colocate, on the opposite strand, with the gene
      encoding ssrA, a hybrid of tRNA and mRNA (tmRNA), which is involved in a trans
      translation process related to ribosome rescue and is ubiquitous in bacteria.
      Specific DNA probes were designed and used in real-time PCR assays to follow the
      separate transcriptional responses of the colocated open reading frames (ORFs)
      during transition from exponential to stationary phase, chloramphenicol
      challenge, and syntrophic coculture with Methanococcus jannaschii. TM0504
      transcription did not vary under normal growth conditions. Transcription of the
      tmRNA gene, however, was significantly up-regulated during chloramphenicol
      challenge and in T. maritima bound in exopolysaccharide aggregates during
      methanogenic coculture. The significance of the colocation of ORFs encoding a
      putative signaling peptide and tmRNA in T. maritima is intriguing, since this
      overlapping arrangement (tmRNA associated with putative small ORFs) was found to
      be conserved in at least 181 bacterial genomes sequenced to date. Whether
      peptides related to TM0504 in other bacteria play a role in quorum sensing is not
      yet known, but their ubiquitous colocalization with respect to tmRNA merits
      further examination.

PMID- 16980483
TI  - Biochemical and molecular characterization of the biosynthesis of glutamine and
      glutamate, two major compatible solutes in the moderately halophilic bacterium
      Halobacillus halophilus.
AB  - The moderately halophilic, chloride-dependent bacterium Halobacillus halophilus
      produces glutamate and glutamine as main compatible solutes at external
      salinities of 1.0 to 1.5 M NaCl. The routes for the biosynthesis of these solutes
      and their regulation were examined. The genome contains two genes potentially
      encoding glutamate dehydrogenases and two genes for the small subunit of a
      glutamate synthase, but only one gene for the large subunit. However, the
      expression of these genes was not salt dependent, nor were the corresponding
      enzymatic activities detectable in cell extracts of cells grown at different
      salinities. In contrast, glutamine synthetase activity was readily detectable in
      H. halophilus. Induction of glutamine synthetase activity was strictly salt
      dependent and reached a maximum at 3.0 M NaCl; chloride stimulated the production
      of active enzyme by about 300%. Two potential genes encoding a glutamine
      synthetase, glnA1 and glnA2, were identified. The expression of glnA2 but not of
      glnA1 was increased up to fourfold in cells adapted to high salt, indicating that
      GlnA2 is the glutamine synthetase involved in the synthesis of the solutes
      glutamate and glutamine. Furthermore, expression of glnA2 was stimulated twofold
      by the presence of chloride ions. Chloride exerted an even more pronounced effect
      on the enzymatic activity of preformed enzyme: in the absence of chloride in the
      assay buffer, glutamine synthetase activity was decreased by as much as 90%.
      These data demonstrate for the first time a regulatory role of a component of
      common salt, chloride, in the biosynthesis of compatible solutes.

PMID- 16980484
TI  - Analysis of RNase P protein (rnpA) expression in Bacillus subtilis utilizing
      strains with suppressible rnpA expression.
AB  - Bacterial RNase P is composed of an RNA subunit and a single protein subunit
      (encoded by the rnpB and rnpA genes, respectively). We constructed Bacillus
      subtilis mutant strains that conditionally express the RNase P protein under
      control of the xylose promoter (P(xyl)). In one strain (d7), rnpA expression was
      efficiently repressed in the absence of the inducer xylose, leading to cell
      growth arrest. Growth could be restored by a second functional rnpA allele. This
      is the first RNase P protein knockdown strain, providing the first direct proof
      that the rnpA gene is essential in B. subtilis and, by inference, in other
      bacteria. We further show (i) that, in the wild-type context, rnpA expression is
      attenuated by transcriptional polarity and (ii) that translation of rnpA mRNA in
      B. subtilis can be initiated at two alternative start codons. His-tagged RNase P
      protein variants are functional in vivo and permit purification of in vivo
      assembled holoenzymes by affinity chromatography. Simultaneous expression of
      plasmid-encoded RNase P RNA and His-tagged protein increased RNase P holoenzyme
      yields. Massive overproduction of RNase P protein in strain d7 is compatible with
      cell viability.

PMID- 16980485
TI  - Role of an RNase III binding site in transcription termination at lambda nutL by
      HK022 Nun protein.
AB  - The phage HK022 Nun protein excludes phage lambda by binding nascent lambda pL
      and pR transcripts at nutL and nutR, respectively, and inducing transcription
      termination just downstream of these sites. Termination is more efficient at nutL
      than at nutR. One difference between nutL and nutR is the presence of RNase III
      processing sites (rIII) located immediately promoter distal to lambda nutL. We
      found that deletion of rIII dramatically reduced Nun transcription arrest in
      vitro but had little effect on termination in vivo. However, consistent with the
      in vitro results, overexpression of a transcript carrying nutL and rIII
      efficiently titrated Nun, allowing lambda to grow on a strain that expressed Nun,
      whereas a transcript carrying only nutL or nutL-rIII with nucleotides 97 to 141
      deleted was ineffective. Rnc70, an RNase III mutant that binds but does not
      cleave rIII, also prevented Nun-mediated lambda exclusion. We propose that rIII
      enhances the on-rate of Nun at nutL, stimulating Nun-mediated arrest in vitro. We
      have shown that a specific element in rIII, i.e., box C (G89GUGUGUG), strongly
      enhances arrest on rIII+ templates. Nun-rIII interactions do not stimulate Nun
      termination in vivo, presumably because formation of the Nun-nutL complex is
      normally not rate-limiting in the cell. In contrast to Nun, N is not occluded by
      Rnc70 and is not efficiently titrated by a nutL-rIII transcript.

PMID- 16980486
TI  - Characterization of ExsC and ExsD self-association and heterocomplex formation.
AB  - Expression of the Pseudomonas aeruginosa type III secretion system (T3SS) is
      induced by calcium depletion and is positively regulated by the ExsA
      transcriptional activator and negatively regulated by the ExsD antiactivator.
      Under conditions permissive for expression of the T3SS, the negative regulatory
      activity of ExsD is antagonized by a direct binding interaction with ExsC. In the
      present study, the ExsC-ExsD binding interaction was characterized. Individually,
      both ExsC and ExsD form self-associated complexes, as judged by bacterial
      monohybrid and gel filtration experiments. A mixture of purified ExsC and ExsD
      readily formed a complex that elutes from gel filtration medium as a single
      included peak. The calculated molecular weight of the ExsC-ExsD complex is
      consistent with a complex containing multiple copies of ExsC and ExsD. Isothermic
      titration calorimetry experiments found formation of the ExsC-ExsD complex to be
      thermodynamically favorable, with a Kd of approximately 18 nM and a likely
      binding ratio of 1:1. To identify amino acid residues important for the
      regulatory activities of ExsC and ExsD, self-association, and complex formation,
      charged-cluster mutagenesis was performed. Two of the resulting ExsD charged
      cluster mutants (DM2 and DM3) demonstrated a hyperrepressive phenotype for
      expression of the T3SS. By two-hybrid and copurification assays, the DM3 mutant
      was found to be impaired in its interaction with ExsC. This finding demonstrates
      that the binding of ExsC to ExsD is required for transcriptional induction of the
      T3SS under calcium-limiting growth conditions.

PMID- 16980487
TI  - Comparative genomic evidence for a close relationship between the dimorphic
      prosthecate bacteria Hyphomonas neptunium and Caulobacter crescentus.
AB  - The dimorphic prosthecate bacteria (DPB) are alpha-proteobacteria that reproduce
      in an asymmetric manner rather than by binary fission and are of interest as
      simple models of development. Prior to this work, the only member of this group
      for which genome sequence was available was the model freshwater organism
      Caulobacter crescentus. Here we describe the genome sequence of Hyphomonas
      neptunium, a marine member of the DPB that differs from C. crescentus in that H.
      neptunium uses its stalk as a reproductive structure. Genome analysis indicates
      that this organism shares more genes with C. crescentus than it does with
      Silicibacter pomeroyi (a closer relative according to 16S rRNA phylogeny), that
      it relies upon a heterotrophic strategy utilizing a wide range of substrates,
      that its cell cycle is likely to be regulated in a similar manner to that of C.
      crescentus, and that the outer membrane complements of H. neptunium and C.
      crescentus are remarkably similar. H. neptunium swarmer cells are highly motile
      via a single polar flagellum. With the exception of cheY and cheR, genes required
      for chemotaxis were absent in the H. neptunium genome. Consistent with this
      observation, H. neptunium swarmer cells did not respond to any chemotactic
      stimuli that were tested, which suggests that H. neptunium motility is a random
      dispersal mechanism for swarmer cells rather than a stimulus-controlled
      navigation system for locating specific environments. In addition to providing
      insights into bacterial development, the H. neptunium genome will provide an
      important resource for the study of other interesting biological processes
      including chromosome segregation, polar growth, and cell aging.

PMID- 16980488
TI  - Characterization of the genetic components of Streptomyces lividans linear
      plasmid SLP2 for replication in circular and linear modes.
AB  - The nucleotide sequence of Streptomyces lividans linear plasmid SLP2 consists of
      50,410 bp (C. H. Huang, C. Y. Chen, H. H. Tsai, C. Chen, Y. S. Lin, and C. W.
      Chen, Mol. Microbiol. 47:1563-1576, 2003). Here we report that the basic SLP2
      locus for plasmid replication in circular mode resembles that of Streptomyces
      linear plasmids pSLA2 and SCP1 and comprises iterons(SLP2) and the adjacent
      rep(SLP2) gene. More efficient replication additionally required the 47-bp
      sequence between bp 581 and 628 upstream of the iterons. Replacement of either
      the iterons or the rep gene of SLP2 by the corresponding genes of pSLA2 or SCP1
      still allows propagation in Streptomyces, although the transformation frequencies
      were 3 orders of magnitude lower than the original plasmids, suggesting that
      these plasmids share similar replication mechanisms. To replicate SLP2 in linear
      mode, additional SLP2 loci--either mtap(SLP2)/tpg(SLP2) or mtap(SLP2)/ilrA(SLP2)-
      were required. IlrA(SLP2) protein binds specifically to the iterons(SLP2) in
      vitro. Interactions were detected between these SLP2-borne replication proteins
      (Mtap(SLP2), Tpg(SLP2), and IlrA(SLP2)) and the telomeric replication proteins
      (TpgL, TapL, and TpgL) of the S. lividans chromosome, respectively, but the SLP2
      proteins failed to interact. These results suggest that SLP2 recruits
      chromosomally encoded replication proteins for its telomere replication.

PMID- 16980489
TI  - Comparative genomic hybridization analysis of Enterococcus faecalis:
      identification of genes absent from food strains.
AB  - Enterococcus faecalis, a member of the natural microbiota of animal and human
      intestinal tracts, is also present as a natural contaminant in a variety of
      fermented foods. Over the last decade, E. faecalis has emerged as a major cause
      of nosocomial infections. We investigated the genetic diversity in 30 clinical
      and food isolates, including strains V583 and MMH594, in order to determine
      whether clinical and food isolates could be distinguished. Data were obtained
      using comparative genomic hybridization and specific PCR with a total of 202
      probes of E. faecalis, selected using the available V583 genome sequence and part
      of the MMH594 pathogenicity island. The cognate genes encoded mainly exported
      proteins. Hybridization data were analyzed by a two-component mixture model that
      estimates the probability of any given gene to be either present or absent in the
      strains. A total of 78 genes were found to be variable, as they were absent in at
      least one isolate. Most of the variable genes were clustered in regions that, in
      the published V583 sequence, related to prophages or mobile genetic elements. The
      variable genes were distributed in three main groups: (i) genes equally
      distributed between clinical and dairy food isolates, (ii) genes absent from
      dairy food-related isolates, and (iii) genes present in MMH594 and V583 strains
      only. Further analysis of the distribution of the last gene group in 70 other
      isolates confirmed that six of the probed genes were always absent in dairy food
      related isolates, whereas they were detected in clinical and/or commensal
      isolates. Two of them corresponded to prophages that were not detected in the
      cognate isolates, thus possibly extending the number of genes absent from dairy
      food isolates. Genes specifically detected in clinical isolates may prove
      valuable for the development of new risk assessment markers for food safety
      studies and for identification of new factors that may contribute to host
      colonization or infection.

PMID- 16980490
TI  - Alterations of cellular physiology in Escherichia coli in response to oxidative
      phosphorylation impaired by defective F1-ATPase.
AB  - The physiological changes in an F1-ATPase-defective mutant of Escherichia coli
      W1485 growing in a glucose-limited chemostat included a decreased growth yield
      (60%) and increased specific rates of both glucose consumption (168%) and
      respiration (171%). Flux analysis revealed that the mutant showed approximately
      twice as much flow in glycolysis but only an 18% increase in the tricarboxylic
      acid (TCA) cycle, owing to the excretion of acetate, where most of the increased
      glycolytic flux was directed. Genetic and biochemical analyses of the mutant
      revealed the downregulation of many TCA cycle enzymes, including citrate
      synthase, and the upregulation of the pyruvate dehydrogenase complex in both
      transcription and enzyme activities. These changes seemed to contribute to
      acetate excretion in the mutant. No transcriptional changes were observed in the
      glycolytic enzymes, despite the enhanced glycolysis. The most significant
      alterations were found in the respiratory-chain components. The total activity of
      NADH dehydrogenases (NDHs) and terminal oxidases increased about twofold in the
      mutant, which accounted for its higher respiration rate. These changes arose
      primarily from the increased (3.7-fold) enzyme activity of NDH-2 and an increased
      amount of cytochrome bd in the mutant. Transcriptional upregulation appeared to
      be involved in these phenomena. As NDH-2 cannot generate an electrochemical
      gradient of protons and as cytochrome bd is inferior to cytochrome bo3 in this
      ability, the mutant was able to recycle NADH at a higher rate than the parent and
      avoid generating an excess proton-motive force. We discuss the physiological
      benefits of the alterations in the mutant.

PMID- 16980492
TI  - PhoP-induced genes within Salmonella pathogenicity island 1.
AB  - The invasive pathogen Salmonella enterica has evolved a sophisticated device that
      allows it to enter nonphagocytic host cells. This process requires the expression
      of Salmonella pathogenicity island 1 (SPI-1), which encodes a specialized type
      III protein secretion system (TTSS). This TTSS delivers a set of effectors that
      produce a marked rearrangement of the host cytoskeleton, generating a profuse
      membrane ruffling at the site of interaction, driving bacterial entry. It has
      been shown that the PhoP/PhoQ two-component system represses the expression of
      the SPI-1 machinery by down-regulating the transcription of its master regulator,
      HilA. In this work, we reveal the presence of a PhoP-activated operon within SPI
      1. This operon is composed of the orgB and orgC genes, which encode a protein
      that interacts with the InvC ATPase and a putative effector protein of the TTSS,
      respectively. Under PhoP-inducing conditions, expression of this operon is
      directly activated by the phosphorylated form of the response regulator, which
      recognizes a PhoP box located at the -35 region relative to the transcription
      start site. Additionally, under invasion-inducing conditions, orgBC expression is
      driven both by the prgH promoter, induced by the SPI-1 master regulator HilA, and
      by the directly controlled PhoP/PhoQ promoter. Together, these results indicate
      that in contrast to the rest of the genes encompassed in the SPI-1 locus, orgBC
      is expressed during and after Salmonella entry into its host cell, and they
      suggest a role for the products of this operon after host cell internalization.

PMID- 16980491
TI  - The atlA operon of Streptococcus mutans: role in autolysin maturation and cell
      surface biogenesis.
AB  - The Smu0630 protein (AtlA) was recently shown to be involved in cell separation,
      biofilm formation, and autolysis. Here, transcriptional studies revealed that
      atlA is part of a multigene operon under the control of at least three promoters.
      The morphology and biofilm-forming capacity of a nonpolar altA mutant could be
      restored to that of the wild-type strain by adding purified AtlA protein to the
      medium. A series of truncated derivatives of AtlA revealed that full activity
      required the C terminus and repeat regions. AtlA was cell associated and readily
      extractable from with sodium dodecyl sulfate. Of particular interest, the surface
      protein profile of AtlA-deficient strains was dramatically altered compared to
      the wild-type strain, as was the nature of the association of the multifunctional
      adhesin P1 with the cell wall. In addition, AtlA-deficient strains failed to
      develop competence as effectively as the parental strain. Mutation of thmA, which
      can be cotranscribed with atlA and encodes a putative pore-forming protein,
      resulted in a phenotype very similar to that of the AtlA-deficient strain. ThmA
      was also shown to be required for efficient processing of AtlA to its mature
      form, and treatment of the thmA mutant strain with full-length AtlA protein did
      not restore normal cell separation and biofilm formation. The effects of mutating
      other genes in the operon on cell division, biofilm formation, or AtlA biogenesis
      were not as profound. This study reveals that AtlA is a surface-associated
      protein that plays a critical role in the network connecting cell surface
      biogenesis, biofilm formation, genetic competence, and autolysis.

PMID- 16980493
TI  - The TadV protein of Actinobacillus actinomycetemcomitans is a novel aspartic acid
      prepilin peptidase required for maturation of the Flp1 pilin and TadE and TadF
      pseudopilins.
AB  - The tad locus of Actinobacillus actinomycetemcomitans encodes genes for the
      biogenesis of Flp pili, which allow the bacterium to adhere tenaciously to
      surfaces and form strong biofilms. Although tad (tight adherence) loci are
      widespread among bacterial and archaeal species, very little is known about the
      functions of the individual components of the Tad secretion apparatus. Here we
      characterize the mechanism by which the pre-Flp1 prepilin is processed to the
      mature pilus subunit. We demonstrate that the tadV gene encodes a prepilin
      peptidase that is both necessary and sufficient for proteolytic maturation of
      Flp1. TadV was also found to be required for maturation of the TadE and TadF
      pilin-like proteins, which we term pseudopilins. Using site-directed mutagenesis,
      we show that processing of pre-Flp1, pre-TadE, and pre-TadF is required for
      biofilm formation. Mutation of a highly conserved glutamic acid residue at
      position +5 of Flp1, relative to the cleavage site, resulted in a processed pilin
      that was blocked in assembly. In contrast, identical mutations in TadE or TadF
      had no effect on biofilm formation, indicating that the mechanisms by which Flp1
      pilin and the pseudopilins function are distinct. We also determined that two
      conserved aspartic acid residues in TadV are critical for function of the
      prepilin peptidase. Together, our results indicate that the A.
      actinomycetemcomitans TadV protein is a member of a novel subclass of
      nonmethylating aspartic acid prepilin peptidases.

PMID- 16980494
TI  - Flagella of Pyrococcus furiosus: multifunctional organelles, made for swimming,
      adhesion to various surfaces, and cell-cell contacts.
AB  - Pyrococcus furiosus ("rushing fireball") was named for the ability of this
      archaeal coccus to rapidly swim at its optimal growth temperature, around 100
      degrees C. Early electron microscopic studies identified up to 50 cell surface
      appendages originating from one pole of the coccus, which have been called
      flagella. We have analyzed these putative motility organelles and found them to
      be composed primarily (>95%) of a glycoprotein that is homologous to flagellins
      from other archaea. Using various electron microscopic techniques, we found that
      these flagella can aggregate into cable-like structures, forming cell-cell
      connections between ca. 5% of all cells during stationary growth phase. P.
      furiosus cells could adhere via their flagella to carbon-coated gold grids used
      for electron microscopic analyses, to sand grains collected from the original
      habitat (Porto di Levante, Vulcano, Italy), and to various other surfaces. P.
      furiosus grew on surfaces in biofilm-like structures, forming microcolonies with
      cells interconnected by flagella and adhering to the solid supports. Therefore,
      we concluded that P. furiosus probably uses flagella for swimming but that the
      cell surface appendages also enable this archaeon to form cable-like cell-cell
      connections and to adhere to solid surfaces.

PMID- 16980495
TI  - Genomic analysis of Pseudomonas aeruginosa phages LKD16 and LKA1: establishment
      of the phiKMV subgroup within the T7 supergroup.
AB  - Lytic Pseudomonas aeruginosa phages LKD16 and LKA1 were locally isolated and
      morphologically classified as Podoviridae. While LKD16 adsorbs weakly to its
      host, LKA1 shows efficient adsorption (ka = 3.9 x 10(-9) ml min(-1)). LKA1,
      however, displays a narrow host range on clinical P. aeruginosa strains compared
      to LKD16. Genome analysis of LKD16 (43,200 bp) and LKA1 (41,593 bp) revealed that
      both phages have linear double-stranded DNA genomes with direct terminal repeats
      of 428 and 298 bp and encode 54 and 56 genes, respectively. The majority of the
      predicted structural proteins were experimentally confirmed as part of the phage
      particle using mass spectrometry. Phage LKD16 is closely related to bacteriophage
      phiKMV (83% overall DNA homology), allowing a more thoughtful gene annotation of
      both genomes. In contrast, LKA1 is more distantly related, lacking significant
      DNA homology and showing protein similarity to phiKMV in 48% of its gene
      products. The early region of the LKA1 genome has diverged strongly from phiKMV
      and LKD16, and intriguing differences in tail fiber genes of LKD16 and LKA1
      likely reflect the observed discrepancy in infection-related properties.
      Nonetheless, general genome organization is clearly conserved among phiKMV,
      LKD16, and LKA1. The three phages carry a single-subunit RNA polymerase gene
      adjacent to the structural genome region, a feature which distinguishes them from
      other members of the T7 supergroup. Therefore, we propose that phiKMV represents
      an independent and widespread group of lytic P. aeruginosa phages within the T7
      supergroup.

PMID- 16980496
TI  - Rem, a new transcriptional activator of motility and chemotaxis in Sinorhizobium
      meliloti.
AB  - The expression of 51 known genes clustered in the flagellar regulon of
      Sinorhizobium meliloti is organized as a three-class hierarchy: class IA
      comprises the master regulatory genes, visN and visR; class II, controlled by
      VisNR, comprises flagellar assembly and motility genes; and class III comprises
      flagellin and chemotaxis genes requiring class II for expression. The expression
      of visN-visR is constitutive throughout growth, whereas that of class II and
      class III genes is limited to exponential growth. A new OmpR-like, 25-kDa
      transcription factor, Rem, whose synthesis is confined to exponential growth, was
      shown to positively control swimming motility. No phosphorylation of the receiver
      domain of Rem was required for its activity. Gene expression in tester strains
      with known deficiencies placed the rem gene (class IB) below visN-visR (class IA)
      and above class II genes in the regulatory cascade. Footprinting analysis
      demonstrated that the Rem protein binds to class II gene promoters as well as to
      its own promoter, indicating that this protein is autoregulatory. An alignment of
      the Rem-protected DNA sequences revealed a conserved binding motif of imperfect
      tandem repeats overlapping a predicted -35 promoter box by 3 bp. This new
      promoter was confirmed by mapping the transcription start site of a typical class
      II gene, flgB, 5 nucleotides downstream of the -10 promoter box. The
      transcription of rem is under dual control of an upstream (Rem-activated) class
      II-type promoter and a downstream (VisNR-activated) sigma70-like promoter. The
      central role of Rem as the growth-dependent transcriptional activator
      intermediate between the master regulator, VisNR, and the flagellar and motility
      genes is a new distinguishing feature of the S. meliloti regulatory cascade.

PMID- 16980497
TI  - Lipoprotein PssN of Rhizobium leguminosarum bv. trifolii: subcellular
      localization and possible involvement in exopolysaccharide export.
AB  - Surface expression of exopolysaccharides (EPS) in gram-negative bacteria depends
      on the activity of proteins found in the cytoplasmic membrane, the periplasmic
      space, and the outer membrane. pssTNOP genes identified in Rhizobium
      leguminosarum bv. trifolii strain TA1 encode proteins that might be components of
      the EPS polymerization and secretion system. In this study, we have characterized
      PssN protein. Employing pssN-phoA and pssN-lacZ gene fusions and in vivo
      acylation with [3H]palmitate, we demonstrated that PssN is a 43-kDa lipoprotein
      directed to the periplasm by an N-terminal signal sequence. Membrane detergent
      fractionation followed by sucrose gradient centrifugation showed that PssN is an
      outer membrane-associated protein. Indirect immunofluorescence with anti-PssN and
      fluorescein isothiocyanate-conjugated antibodies and protease digestion of
      spheroplasts and intact cells of TA1 provided evidence that PssN is oriented
      towards the periplasmic space. Chemical cross-linking of TA1 and E. coli cells
      overproducing PssN-His6 protein showed that PssN might exist as a homo-oligomer
      of at least two monomers. Investigation of the secondary structure of purified
      PssN-His6 protein by Fourier transform infrared spectroscopy revealed the
      predominant presence of beta-structure; however, alpha-helices were also
      detected. Influence of an increased amount of PssN protein on the TA1 phenotype
      was assessed and correlated with a moderate enhancement of EPS production.

PMID- 16980498
TI  - Dual role of the PhoP approximately P response regulator: Bacillus
      amyloliquefaciens FZB45 phytase gene transcription is directed by positive and
      negative interactions with the phyC promoter.
AB  - Several Bacillus strains secrete phytase, an enzyme catalyzing dephosphorylation
      of myo-inositol hexakisphosphate (phytate). We identified the phyC (phytase) gene
      from environmental Bacillus amyloliquefaciens FZB45 as a member of the phosphate
      starvation-inducible PhoPR regulon. In vivo and in vitro assays revealed that
      PhoP approximately P is essential for phyC transcription. The transcriptional
      start site was identified downstream of a sigmaA-like promoter region located 27
      bp upstream of the probable translation ATG start codon. Inspection of the phyC
      promoter sequence revealed an unusual structure. The -35 and -10 regions are
      separated by a window of 21 bp. A pair of tandemly repeated PhoP TT(T/A/C)ACA
      binding boxes was located within and upstream of the -35 consensus promoter
      region. A single PhoP box was found within the -10 consensus promoter region.
      DNase I footprinting experiments performed with isolated PhoP confirmed that PhoP
      approximately P binds at two sites overlapping with the phyC -35 and -10
      consensus promoter region. While binding of dimeric PhoP approximately P at -35
      is essential for activation of the phyC promoter, binding of PhoP approximately P
      at -10 suppresses promoter activity. A sixfold enhancement of phyC gene
      expression was registered after T:G substitution of nucleotide -13 (mutant
      MUT13), which eliminates PhoP binding at the single PhoP box without impairing
      the -10 consensus sequence. Moreover, MUT13 also expressed phyC during phosphate
      replete growth, suggesting that the repressing effect due to binding of PhoP
      approximately P at -10 was abolished. A model is presented in which transcription
      initiation of phyC is positively and negatively affected by the actual
      concentration of the PhoP approximately P response regulator.

PMID- 16980499
TI  - Mapping essential domains of Mycobacterium smegmatis WhmD: insights into WhiB
      structure and function.
AB  - A growing body of evidence suggests that the WhiB-like proteins exclusive to the
      GC-rich actinomycete genera play significant roles in pathogenesis and cell
      division. Each of these proteins contains four invariant cysteine residues and a
      conserved helix-turn-helix motif. whmD, the Mycobacterium smegmatis homologue of
      Streptomyces coelicolor whiB, is essential in M. smegmatis, and the conditionally
      complemented mutant M. smegmatis 628-53 undergoes filamentation under
      nonpermissive conditions. To identify residues critical to WhmD function, we
      developed a cotransformation-based assay to screen for alleles that complement
      the filamentation phenotype of M. smegmatis 628-53 following inducer withdrawal.
      Mycobacterium tuberculosis whiB2 and S. coelicolor whiB complemented the defect
      in M. smegmatis 628-53, indicating that these genes are true functional
      orthologues of whmD. Deletion analysis suggested that the N-terminal 67 and C
      terminal 12 amino acid residues are dispensable for activity. Site-directed
      mutagenesis indicated that three of the four conserved cysteine residues (C90,
      C93, and C99) and a conserved aspartate (D71) are essential. Mutations in a
      predicted loop glycine (G111) and an unstructured leucine (L116) were poorly
      tolerated. The region essential for WhmD activity encompasses 6 of the 10
      residues conserved in all seven M. tuberculosis WhiBs, as well as in most members
      of the WhiB family identified thus far. WhmD structure was found to be sensitive
      to the presence of a reducing agent, suggesting that the cysteine residues are
      involved in coordinating a metal ion. Iron-specific staining strongly suggested
      that WhmD contains a bound iron atom. With this information, we have now begun to
      comprehend the functional significance of the conserved sequence and structural
      elements in this novel family of proteins.

PMID- 16980500
TI  - Chromosome rearrangement and diversification of Francisella tularensis revealed
      by the type B (OSU18) genome sequence.
AB  - The gamma-proteobacterium Francisella tularensis is one of the most infectious
      human pathogens, and the highly virulent organism F. tularensis subsp. tularensis
      (type A) and less virulent organism F. tularensis subsp. holarctica (type B) are
      most commonly associated with significant disease in humans and animals. Here we
      report the complete genome sequence and annotation for a low-passage type B
      strain (OSU18) isolated from a dead beaver found near Red Rock, Okla., in 1978. A
      comparison of the F. tularensis subsp. holarctica sequence with that of F.
      tularensis subsp. tularensis strain Schu4 (P. Larsson et al., Nat. Genet. 37:153
      159, 2005) highlighted genetic differences that may underlie different
      pathogenicity phenotypes and the evolutionary relationship between type A and
      type B strains. Despite extensive DNA sequence identity, the most significant
      difference between type A and type B isolates is the striking amount of genomic
      rearrangement that exists between the strains. All but two rearrangements can be
      attributed to homologous recombination occurring between two prominent insertion
      elements, ISFtu1 and ISFtu2. Numerous pseudogenes have been found in the genomes
      and are likely contributors to the difference in virulence between the strains.
      In contrast, no rearrangements have been observed between the OSU18 genome and
      the genome of the type B live vaccine strain (LVS), and only 448 polymorphisms
      have been found within non-transposase-coding sequences whose homologs are intact
      in OSU18. Nonconservative differences between the two strains likely include the
      LVS attenuating mutation(s).

PMID- 16980501
TI  - Structural basis for regioselectivity and stereoselectivity of product formation
      by naphthalene 1,2-dioxygenase.
AB  - Rieske oxygenase (RO) systems are two- and three-component enzyme systems that
      catalyze the formation of cis-dihydrodiols from aromatic substrates. Degradation
      of pollutants in contaminated soil and generation of chiral synthons have been
      the major foci of RO research. Substrate specificity and product regio- and
      stereoselectivity have been shown to vary between individual ROs. While directed
      evolution methods for altering RO function have been successful in the past,
      rational engineering of these enzymes still poses a challenge due to the lack of
      structural understanding. Here we examine the structural changes induced by
      mutation of Phe-352 in naphthalene 1,2-dioxygenase from Pseudomonas sp. strain
      NCIB 9816-4 (NDO-O(9816-4)). Structures of the Phe-352-Val mutant in native form
      and in complex with phenanthrene and anthracene, along with those of wild-type
      NDO-O(9816-4) in complex with phenanthrene, anthracene, and 3-nitrotoluene, are
      presented. Phenanthrene was shown to bind in a different orientation in the Phe
      352-Val mutant active site from that in the wild type, while anthracene was found
      to bind in similar positions in both enzymes. Two orientations of 3-nitrotoluene
      were observed, i.e., a productive and a nonproductive orientation. These
      orientations help explain why NDO-O(9816-4) forms different products from 3
      nitrotoluene than those made from nitrobenzene dioxygenase. Comparison of these
      structures among themselves and with other known ROs bound to substrates reveals
      that the orientation of substrate binding at the active site is the primary
      determinant of product regio- and stereoselectivity.

PMID- 16980502
TI  - FlhF is required for swimming and swarming in Pseudomonas aeruginosa.
AB  - FlhF is a signal recognition particle-like protein present in monotrichous
      bacteria. The loss of FlhF in various bacteria results in decreased transcription
      of class II, III, or IV flagellar genes, leads to diminished or absent motility,
      and results in the assembly of flagella at nonpolar locations on the cell
      surface. In this work, we demonstrate that the loss of FlhF results in defective
      swimming and swarming motility of Pseudomonas aeruginosa. The FlhF protein
      localizes to the flagellar pole; in the absence of FlhF, flagellar assembly
      occurs but is no longer restricted to the pole. DeltaflhF bacteria swim at lower
      velocities than wild-type bacteria in liquid media and can no longer swarm when
      assayed under standard swarming conditions (0.5% agar). However, DeltaflhF
      bacteria regain swarming behavior when plated on 0.3% agar. DeltaflhF organisms
      show decreased transcription and expression of flagellin (FliC) both in liquid
      media and on swarming plates compared to wild-type bacteria. However, changes in
      flagellin expression do not explain the different motility patterns observed for
      DeltaflhF bacteria. Instead, the aberrant placement of flagella in DeltaflhF
      bacteria may reduce their ability to move this rod-shaped organism effectively.

PMID- 16980503
TI  - Whole-genome transcriptional analysis of chemolithoautotrophic thiosulfate
      oxidation by Thiobacillus denitrificans under aerobic versus denitrifying
      conditions.
AB  - Thiobacillus denitrificans is one of the few known obligate chemolithoautotrophic
      bacteria capable of energetically coupling thiosulfate oxidation to
      denitrification as well as aerobic respiration. As very little is known about the
      differential expression of genes associated with key chemolithoautotrophic
      functions (such as sulfur compound oxidation and CO2 fixation) under aerobic
      versus denitrifying conditions, we conducted whole-genome, cDNA microarray
      studies to explore this topic systematically. The microarrays identified 277
      genes (approximately 10% of the genome) as differentially expressed using RMA
      (robust multiarray average) statistical analysis and a twofold cutoff. Genes
      upregulated (ca. 6- to 150-fold) under aerobic conditions included a cluster of
      genes associated with iron acquisition (e.g., siderophore-related genes), a
      cluster of cytochrome cbb3 oxidase genes, cbbL and cbbS (encoding the large and
      small subunits of form I ribulose 1,5-bisphosphate carboxylase/oxygenase, or
      RubisCO), and multiple molecular chaperone genes. Genes upregulated (ca. 4- to 95
      fold) under denitrifying conditions included nar, nir, and nor genes (associated,
      respectively, with nitrate reductase, nitrite reductase, and nitric oxide
      reductase, which catalyze successive steps of denitrification), cbbM (encoding
      form II RubisCO), and genes involved with sulfur compound oxidation (including
      two physically separated but highly similar copies of sulfide:quinone
      oxidoreductase and of dsrC, associated with dissimilatory sulfite reductase).
      Among genes associated with denitrification, relative expression levels (i.e.,
      degree of upregulation with nitrate) tended to decrease in the order nar > nir >
      nor > nos. Reverse transcription-quantitative PCR analysis was used to validate
      these trends.

PMID- 16980504
TI  - Characterization of adhesion threads of Deinococcus geothermalis as type IV pili.
AB  - Deinococcus geothermalis E50051 forms tenuous biofilms on paper machine surfaces.
      Field emission electron microscopy analysis revealed peritrichous appendages
      which mediated cell-to-surface and cell-to-cell interactions but were absent in
      planktonically grown cells. The major protein component of the extracellular
      extract of D. geothermalis had an N-terminal sequence similar to the fimbrial
      protein pilin annotated in the D. geothermalis DSM 11300 draft sequence. It also
      showed similarity to the type IV pilin sequence of D. radiodurans and several
      gram-negative pathogenic bacteria. Other proteins in the extract had N-terminal
      sequences identical to D. geothermalis proteins with conservative motifs for
      serine proteases, metallophosphoesterases, and proteins whose function is
      unknown. Periodic acid-Schiff staining for carbohydrates indicated that these
      extracellular proteins may be glycosylated. A further confirmation for the
      presence of glycoconjugates on the cell surface was obtained by confocal laser
      scanning imaging of living D. geothermalis cells stained with Amaranthus caudatus
      lectin, which specifically binds to galactose residues. The results indicate that
      the thread-like appendages of D. geothermalis E50051 are glycosylated type IV
      pili, bacterial attachment organelles which have thus far not been described for
      the genus Deinococcus.

PMID- 16980505
TI  - Modes of regulation of RpoS by H-NS.
AB  - Regulated degradation of RpoS requires RssB and ClpXP protease. Mutations in hns
      increase both RpoS synthesis and stability, causing a twofold increase in
      synthesis and almost complete stabilization of RpoS, independent of effects on
      synthesis and independent of phosphorylation of RssB. This suggests that H-NS
      regulates an RssB inhibitor or inhibitors.

PMID- 16980506
TI  - Identification and characterization of a major Zn(II) resistance determinant of
      Mycobacterium smegmatis.
AB  - A zinc ion-sensitive mutant of Mycobacterium smegmatis was isolated. The
      transposon insertion was located in zitA (MSMEG0750), a gene coding for a cation
      diffusion facilitator family protein. Zinc ions specifically induced expression
      of zitA. In silico analysis revealed that environmental and opportunistic
      pathogenic species contain higher numbers of cation diffusion facilitator genes
      than do obligate pathogens.

PMID- 16980508
TI  - A beautiful science.

PMID- 16980507
TI  - Does meloxicam increase the incidence of anovulation induced by single
      administration of levonorgestrel in emergency contraception? A pilot study.
AB  - BACKGROUND: Levonorgestrel (LNG) consistently prevents follicular rupture only
      when it is given before the onset of the ovulatory stimulus. As locally
      synthesized prostaglandin (PG) plays a crucial role in follicular rupture and
      cyclooxygenase-2 (cox-2) catalyses the final step of PG synthesis, we reasoned
      that adding a cox-2 inhibitor to LNG would prevent follicular rupture even after
      the ovulatory process had been triggered by the gonadotrophin surge. METHODS:
      Forty-one women were divided into two groups. One was treated when the size of
      the leading follicle was 15-17 mm (n=10) and the other when it was >or=18 mm
      (n=31). Each woman contributed with one cycle treated with LNG 1.5 mg single dose
      plus placebo and another treated with LNG + meloxicam (Melox) 15 mg, in a
      randomized order. Serial blood sampling for the assay of LH and follicular
      monitoring by transvaginal ultrasound were performed before and after treatment.
      RESULTS: Follicular rupture failed to occur within the 5-day period that followed
      treatment in 50 and 70% of cycles treated with LNG + Placebo and LNG + Melox,
      respectively, in the 15-17 mm group (P=0.15) and in 16 and 39% of cycles treated
      with LNG + Placebo and LNG + Melox, respectively, in the >or=18 mm group (P <
      0.052). The overall proportion of cycles with no follicular rupture or ovulatory
      dysfunction increased significantly by the addition of Melox to LNG (66 versus
      88%, P < 0.012; n=41-matched pairs). CONCLUSIONS: The trend towards increased
      incidence of no follicular rupture when Melox was combined with LNG suggests that
      the addition of a cox-2 inhibitor has the potential to improve the contraceptive
      efficacy of LNG by a pre-fertilization effect.

PMID- 16980509
TI  - HMGB1-secreting capacity of multiple cell lineages revealed by a novel HMGB1
      ELISPOT assay.
AB  - High mobility group box protein 1 (HMGB1) exerts different biological functions
      dependent on its cellular localization. Nuclear HMGB1 maintains chromatin
      architecture and is required for undisturbed transcription activity, and
      extracellularly released HMGB1 mediates inflammation and tissue regeneration. A
      present paucity of readily accessible methods to quantify released HMGB1
      represents a problem concerning the exploration of HMGB1 biology. We have now
      developed a HMGB1-specific ELISPOT assay enabling enumeration of individual HMGB1
      releasing cells. The method also allows automated, semiquantitative assessment of
      released HMGB1 by evaluating areas of single HMGB1 spots. Actively secreted HMGB1
      as well as cells passively releasing the protein following necrotic cell death
      are visualized distinctly using this ELISPOT assay. Kinetics of HMGB1 secretion
      after different stimuli was studied using cell lines of various lineages. IFN
      gamma already induced substantial HMGB1 secretion from the monocytic cell line
      RAW 264.7 within 24 h and even more so after 48 h. LPS only stimulated a modest
      HMGB1 release within 24 h, but this increased considerably by 48 h. TNF-induced
      HMGB1 release was unexpectedly low. Mast cells, which share the secretory,
      lysosomal pathway with macrophages/monocytes, did not secrete HMGB1 in response
      to any studied mode of activation. Most transformed cells overexpress HMGB1, but
      the ELISPOT assay revealed that all transformed cell lines will not actively
      secrete the protein. We believe the ELISPOT method provides a novel tool to study
      pathways promoting or inhibiting HMGB1 secretion.

PMID- 16980510
TI  - CD4(+) T cells stimulate memory CD8(+) T cell expansion via acquired pMHC I
      complexes and costimulatory molecules, and IL-2 secretion.
AB  - The rapid and efficient expansion of CD8(+) memory T cells after the second
      encounter with a pathogen constitutes a hallmark trait of adaptive immunity. Yet,
      the contribution of CD4(+) T cells to the expansion of memory CD8(+) T cells
      remains the subject of controversy. Here, we show that, antigen-specific CD4(+) T
      cells, once activated by dendritic cells (DC) in vitro, have the capacity to
      stimulate expansion of memory CD8(+) T cells in vivo. The memory CD8(+) T cell
      expansion triggered by active CD4(+) T cells are mediated through DC-derived MHC
      I/peptide complexes and CD80 molecules displayed on the active CD4(+) T cells,
      with the involvement of IL-2 secreted by the active CD4(+) T cells. These results
      highlight a previously undescribed role of active CD4(+) T cells in triggering
      expansion of memory CD8(+) T cells.

PMID- 16980511
TI  - Targeted in vivo expression of IFN-gamma-inducible protein 10 induces specific
      antitumor activity.
AB  - Although it is known that the chemoattractant effect of IFN-gamma inducible
      protein 10 (IP-10), a CXC chemokine (CXCL10), plays an important role in T cell
      mediated antitumor immunity in vivo, whether IP-10 is involved in modulating the
      proliferation, survival and functional activation of tumor-specific T cells
      remains poorly investigated. Using an experimental mouse tumor model, we
      demonstrated that the in vivo growth of 4T1 tumor cells harboring IP-10 gene (4T1
      IP-10) was inhibited. Mice inoculated with 4T1-IP-10 tumor cells expressing
      functional IP-10 survived over 90 days, whereas mice injected with control
      parental 4T1 cells and mice of control 4T1 cells transduced with control plasmid
      all succumbed to the tumor by day 38 after tumor inoculation. Mechanical analysis
      showed that targeted expression of IP-10 in 4T1 tumor cells markedly enhanced the
      infiltration of tumor-specific T cells into the 4T1-IP-10 tumor. These tumor
      infiltrating T lymphocytes (TILs) recruited by IP-10 were potent cytolytic
      killers against 4T1 tumor cells and were able to proliferate and produce high
      levels of IFN-gamma in response to 4T1 cells. In vivo administration of IP-10
      recruited TILs induced vigorous proliferation of these TILs in situ in the 4T1-IP
      10 tumor but not in the 4T1-pcDNA3 and parental 4T1 tumors. Furthermore, culture
      of TILs together with recombinant IP-10 significantly enhanced the proliferation
      and expansion of IP-10-recruited TILs in response to 4T1 tumor antigens. These
      results suggest that IP-10 is not only able to chemoattract tumor-specific T
      cells into the local tissue, but also enhance the proliferation, survival, and
      functional activation of these TILs, leading to the tumor regression. Thus,
      targeted expression of IP-10 in vivo will allow for the development of a novel
      approach for immunotherapy of tumor.

PMID- 16980512
TI  - Pivotal advance: analysis of proinflammatory activity of highly purified
      eukaryotic recombinant HMGB1 (amphoterin).
AB  - HMGB1 (amphoterin) is a 30-kDa heparin-binding protein that mediates
      transendothelial migration of monocytes and has proinflammatory cytokine-like
      activities. In this study, we have investigated proinflammatory activities of
      both highly purified eukaryotic HMGB1 and bacterially produced recombinant HMGB1
      proteins. Mass analyses revealed that recombinant eukaryotic HMGB1 has an
      intrachain disulphide bond. In mass analysis of tissue-derived HMGB1, two forms
      were detected: the carboxyl terminal glutamic acid residue lacking form and a
      full-length form. Cell culture studies indicated that both eukaryotic and
      bacterial HMGB1 proteins induce TNF-alpha secretion and nitric oxide release from
      mononuclear cells. Affinity chromatography analysis revealed that HMGB1 binds
      tightly to proinflammatory bacterial substances. A soluble proinflammatory
      substance was separated from the bacterial recombinant HMGB1 by chloroform
      methanol treatment. HMGB1 interacted with phosphatidylserine in both solid-phase
      binding and cell culture assays, suggesting that HMGB1 may regulate
      phosphatidylserine-dependent immune reactions. In conclusion, HMGB1 polypeptide
      has a weak proinflammatory activity by itself, and it binds to bacterial
      substances, including lipids, that may strengthen its effects.

PMID- 16980513
TI  - Dual-loop circuits in postoperative atrial macro re-entrant tachycardias.
AB  - BACKGROUND: Patients may develop dual-loop re-entrant atrial arrhythmias late
      after open-heart surgery, and mapping and catheter ablation remain challenging
      despite computer-assisted mapping techniques. OBJECTIVES: The purpose of the
      study was to demonstrate the prevalence and characteristics of dual-loop re
      entrant arrhythmias, and to define the optimal mapping and ablation strategy.
      METHODS: 40 consecutive patients (mean (SD) age 52 (12) years) with intra-atrial
      re-entrant tachycardia (IART) after open-heart surgery (with an incision of the
      right atrial free wall) were studied. Dual-loop IART was defined as the presence
      of two simultaneous atrial circuits. After an abrupt tachycardia change during
      radiofrequency ablation, electrical disconnection of the targeted re-entry
      isthmus from the remaining circuit was demonstrated by entrainment mapping.
      Furthermore, the second circuit loop was localised using electroanatomical
      mapping and/or entrainment mapping. RESULTS: Dual-loop IART was demonstrated in
      eight (20%, 5 patients with congenital heart disease, 3 with acquired heart
      disease) patients. Dual-loop IART included an isthmus-dependant atrial flutter
      combined with a re-entry related to the atriotomy scar. The diagnosis of dual
      loop IART required the comparison of entrainment mapping before and after
      tachycardia modification. Overall, 35 patients had successful radiofrequency
      ablation (88%). Success rates were lower in patients with dual-loop IART than in
      patients without dual-loop IART. Ablation failures in three patients with dual
      loop IART were related to the inability to properly transect the second
      tachycardia isthmus in the right atrial free wall. CONCLUSIONS: Dual-loop IART is
      relatively common after heart surgery involving a right atriotomy. Abrupt
      tachycardia change and specific entrainment mapping manoeuvres demonstrate these
      circuits. Electroanatomical mapping appears to be important to assist catheter
      ablation of periatriotomy circuits.

PMID- 16980514
TI  - Reversible microvascular dysfunction coupled with persistent myocardial
      dysfunction: implications for post-infarct left ventricular remodelling.
AB  - BACKGROUND: Recent studies have shown that microvascular dysfunction after
      myocardial infarction is a dynamic phenomenon. AIMS: To evaluate the implications
      of dynamic changes in microvascular dysfunction on contractile recovery and left
      ventricular remodelling, and to identify the ideal timing of assessment of such
      microvascular dysfunction. METHODS AND RESULTS: In 39 patients with a first
      myocardial infarction who underwent successful percutaneous coronary
      intervention, microvascular dysfunction was studied by myocardial contrast
      echocardiography (MCE) at 24 h, 1 week and 3 months after the procedure. Real
      time MCE was performed by contrast pulse sequencing and intravenous Sonovue. 14
      patients exhibited left ventricular remodelling at 3 months (>20% increase in
      left ventricular end-diastolic volume, group B), whereas 25 did not (group A).
      Microvascular dysfunction was similar in the two groups at 24 h and improved in
      group A only, being significantly better than that of group B at 1 week (p<0.05)
      and 3 months (p<0.005). Improvement in microvascular dysfunction was not
      associated with improvement in wall motion in the same segments. With
      multivariate analysis including all echocardiographic variables, microvascular
      dysfunction at 1 week was found to be the only independent predictor of left
      ventricular remodelling (p<0.01). With a cut-off value of 1.4, 1-week
      microvascular dysfunction predicts left ventricular remodelling with sensitivity
      and specificity of 73%. CONCLUSIONS: Improvement in microvascular dysfunction
      occurs early after myocardial infarction, although it is not associated with a
      parallel improvement in wall motion but is beneficial in preventing left
      ventricular remodelling. Accordingly, 1-week microvascular dysfunction is a
      powerful and independent predictor of left ventricular remodelling.

PMID- 16980515
TI  - The additional value of patient-reported health status in predicting 1-year
      mortality after invasive coronary procedures: a report from the Euro Heart Survey
      on Coronary Revascularisation.
AB  - OBJECTIVE: Self-perceived health status may be helpful in identifying patients at
      high risk for adverse outcomes. The Euro Heart Survey on Coronary
      Revascularization (EHS-CR) provided an opportunity to explore whether impaired
      health status was a predictor of 1-year mortality in patients with coronary
      artery disease (CAD) undergoing angiographic procedures. METHODS: Data from the
      EHS-CR that included 5619 patients from 31 member countries of the European
      Society of Cardiology were used. Inclusion criteria for the current study were
      completion of a self-report measure of health status, the EuroQol Questionnaire
      (EQ-5D) at discharge and information on 1-year follow-up, resulting in a study
      population of 3786 patients. RESULTS: The 1-year mortality was 3.2% (n = 120).
      Survivors reported fewer problems on the five dimensions of the EQ-5D as compared
      with non-survivors. A broad range of potential confounders were adjusted for,
      which reached a p<0.10 in the unadjusted analyses. In the adjusted analyses,
      problems with self-care (OR 3.45; 95% CI 2.14 to 5.59) and a low rating (< or
      =60) on health status (OR 2.41; 95% CI 1.47 to 3.94) were the most powerful
      independent predictors of mortality, among the 22 clinical variables included in
      the analysis. Furthermore, patients who reported no problems on all five
      dimensions had significantly lower 1-year mortality rates (OR 0.47; 95% CI 0.28
      to 0.81). CONCLUSIONS: This analysis shows that impaired health status is
      associated with a 2-3-fold increased risk of all-cause mortality in patients with
      CAD, independent of other conventional risk factors. These results highlight the
      importance of including patients' subjective experience of their own health
      status in the evaluation strategy to optimise risk stratification and management
      in clinical practice.

PMID- 16980516
TI  - Long-term oral bosentan treatment in patients with pulmonary arterial
      hypertension related to congenital heart disease: a 2-year study.
AB  - OBJECTIVE: To evaluate the long-term clinical and exercise effect of chronic oral
      administration of the non-selective endothelin receptor antagonist bosentan in
      patients with pulmonary arterial hypertension (PAH) related to congenital heart
      disease (CHD). DESIGN: Extension of a preceding prospective non-randomised open
      clinical study on bosentan treatment in PAH related to CHD. SETTING: A tertiary
      referral centre for cardiology. PATIENTS: 19 of the original 21 patients of mean
      (standard deviation (SD)) age 22 (3) years (13 with Eisenmenger syndrome) in
      World Health Organization (WHO) class II-IV and having a mean (SD) oxygen
      saturation of 87 (2) %. INTERVENTION: Patients received bosentan treatment for
      2.4 (0.1) years and underwent clinical and exercise evaluation at baseline, 16
      weeks and 2 years of treatment, with haemodynamic assessment at baseline and 16
      weeks. RESULTS: All patients remained stable with sustained subjective clinical
      and WHO class improvement (p<0.01) at 16 weeks and 2 years of treatment without
      significant side effects or changes in oxygen saturation. After the initial 16
      week improvement (p<0.05) in peak oxygen consumption and exercise duration at
      treadmill test, and walking distance and Borg dyspnoea index at 6-min walk test,
      all exercise parameters appeared to return to their baseline values at 2 years of
      follow-up. CONCLUSIONS: Long-term bosentan treatment in patients with PAH related
      to CHD is safe and induces clinical stability and improvement, but the objective
      exercise values appear to slowly return to baseline. Larger studies on long-term
      endothelin receptor antagonism including quality of life assessment are needed to
      evaluate the therapeutic role of bosentan in this population.

PMID- 16980517
TI  - Outcome of percutaneous coronary intervention in hospitals with and without on
      site cardiac surgery standby.
AB  - OBJECTIVE: To compare characteristics and outcome of patients undergoing
      percutaneous coronary intervention (PCI) in clinics with (WSB) or without (NOSB)
      on-site cardiac surgery backup. DESIGN: Analysis according to hospital, type of
      prospectively collected data of all patients who underwent PCI during 2000-3.
      SETTING: The Swedish Coronary Angiography and Angioplasty Registry covers all PCI
      procedures performed in Sweden. PATIENTS: 34,363 patients underwent PCI between
      January 2000 and December 2003. 8838 procedures were performed in NOSB (mean age
      of patients was 64.5 years) hospitals and 25,525 in WSB (mean age of patients was
      64.1 years) hospitals (p = 0.002). RESULTS: More patients in NOSB hospitals had
      diabetes (17.8% vs 16.8%; p = 0.03). Other clinical characteristics (previous
      infarct, previous coronary artery bypass graft (CABG)) also showed a tendency
      towards worse patients being treated in NOSB hospitals. However, there was a
      higher percentage of patients with ST-segment elevation myocardial infarction
      (18% vs 9.7%; p<0.01) in WSB hospitals. After adjusting for differences in
      baseline risk no significant differences regarding outcome (30-day mortality, 1
      year mortality, stroke and emergency CABG) were observable between WSB and NOSB
      hospitals. This applied to elective and non-elective procedures. CONCLUSIONS: On
      the basis of these data it does not seem warranted to recommend against
      percutaneous transluminal coronary angioplasty in NOSB hospitals.

PMID- 16980518
TI  - Echocardiography-based score to predict outcome after renal transplantation.
AB  - BACKGROUND: Given the high cardiac mortality of renal transplant recipients,
      identification of high-risk patients is important to offer appropriate treatment
      before transplantation. AIM: To determine patients with high mortality after
      renal transplantation despite selection according to current criteria. METHODS:
      Preoperative parameters were collected from 203 renal transplant recipients over
      a follow-up time of 3.6 (1.9) years. The primary end point was all-cause
      mortality. RESULTS: 22 deaths (11%) and 12 cardiac failures (6%) were observed.
      Non-survivors were older (p< or =0.001), had larger left ventricular end-systolic
      diameter (LVSD) (p< or =0.001) and end-diastolic diameter (p = 0.002), and lower
      ejection fraction (p< or =0.001). Left ventricular mass index (p = 0.001),
      maximal wall thickness (p = 0.006) and the proportion with mitral annular
      calcification (p = 0.001) were significantly higher in the non-survivors. The
      risk factors for ischaemic heart disease and exercise test data were not
      significantly different between the two groups. Four independent predictors of
      mortality after renal transplantation were identified: age > or =50 years (p =
      0.002), LVESD > or =3.5 cm (p = 0.002), maximal wall thickness > or =1.4 cm (p =
      0.014) and mitral annular calcification (p = 0.036). The 5-year survival
      estimates for 0, 1, 2 and 3 prognostic factors were 96%, 86%, 69% and 38%,
      respectively. No patient had four prognostic factors. In patients > or =50 years,
      the 5-year survival estimates for 0, 1 and 2 additional prognostic factors were
      73%, 45% and 18%, respectively. CONCLUSION: In addition to selection according to
      current guidelines, age and three conventional echocardiography parameters may
      further improve risk stratification before renal transplantation.

PMID- 16980519
TI  - Use of the Amplatzer muscular ventricular septal defect occluder for closure of
      perimembranous ventricular septal defects.
AB  - BACKGROUND: Transcatheter closure of a perimembranous ventricular septal defect
      (PmVSD) is usually performed with an asymmetric Amplatzer occluder, which is not
      an ideal device. Experience with the use of the Amplatzer muscular ventricular
      septal defect occluder (MVSO) to close selected PmVSDs is presented. SETTING: Two
      tertiary referral centres for paediatric cardiology in two countries. OBJECTIVE:
      To look at the safety and efficacy of the application of the MVSO in patients
      with appropriate PmVSD anatomy. PATIENTS AND INTERVENTION: The procedure was
      performed in 10 patients aged 3.2-40 (mean 12.5) years. All had a PmVSD with a
      mean diameter of 5.4 (range 4-11) mm, with an extension towards the muscular
      septum. The mean distance of the defect from the aortic valve was 5.4 (range 4-6)
      mm. In all but one patient, the MVSO was introduced in routine antegrade
      transvenous fashion (4-mm device in one patient, 6-mm device in five, 8 mm in
      two, 10 mm in one, and 12 mm in one). In one patient, the device was deployed by
      retrograde implantation. RESULTS: All procedures except one were performed
      without complications, and complete closure of the VSD was achieved. One patient
      with a residual shunt developed haemolysis, which resolved over 10 days. In three
      patients, trivial, non-progressive tricuspid regurgitation appeared after the
      procedure. No other complications were observed over 1.7 (range 0.2-3.5) years of
      follow-up. CONCLUSION: Application of the MVSO for closure of selected PmVSDs
      seems to be a safe and effective treatment option.

PMID- 16980520
TI  - Volumetric analysis of regional left ventricular function with real-time three
      dimensional echocardiography: validation by magnetic resonance and clinical
      utility testing.
AB  - BACKGROUND: Quantitative information on regional left ventricular volumes from
      real-time three-dimensional echocardiographic (RT3DE) images has significant
      clinical potential but needs validation. AIM: To validate these measurements
      against cardiac magnetic resonance (CMR) and test the feasibility of automated
      detection of regional wall motion (RWM) abnormalities from RT3DE data. METHODS:
      RT3DE (Philips) and CMR (Siemens) images were obtained from 31 patients and
      analysed by using prototype software to semiautomatically calculate indices of
      regional left ventricular function, which were compared between RT3DE and CMR
      (linear regression, Bland-Altman). Additionally, CMR images were reviewed by an
      expert, whose RWM grades were used as a reference for automated classification of
      segments as normal or abnormal from RT3DE and from CMR images. For each modality,
      normal regional ejection fraction (REF) values were obtained from 15 patients
      with normal wall motion. In the remaining 16 patients, REFs were compared with
      thresholds that were derived from patients with normal wall motion and optimised
      using receiver operating characteristic analysis. RESULTS: RT3DE measurements
      resulted in good agreement with CMR. Regional indices calculated in patients with
      normal wall motion varied between segments, but overall were similar between
      modalities. In patients with abnormal wall motion, RWM was graded as abnormal in
      74% segments. CMR and RT3DE thresholds were similar (16-segment average 55 (10)%
      and 56 (7)%, respectively). Automated interpretation resulted in good agreement
      with expert interpretation, similar for CMR and RT3DE (sensitivity 0.85, 0.84;
      specificity 0.81, 0.78; accuracy 0.84, 0.84, respectively). CONCLUSION: Analysis
      of RT3DE data provides accurate quantification of regional left ventricular
      function and allows semiautomated detection of RWM abnormalities, which is as
      accurate as the same algorithm applied to CMR images.

PMID- 16980521
TI  - A comparison of bone-patellar tendon-bone and bone-hamstring tendon-bone
      autografts for anterior cruciate ligament reconstruction.

PMID- 16980522
TI  - Comparisons of original laboratory results and retrospective analysis by real
      time reverse transcriptase-PCR of virological samples collected from confirmed
      cases of foot-and-mouth disease in the UK in 2001.
AB  - There were 2030 designated cases of foot-and-mouth disease (FMD) during the
      course of the epidemic in the UK in 2001 (including four from Northern Ireland).
      Samples from 1720 of the infected premises (IPs) were received in the laboratory
      and examined for either the presence of FMD virus (virological samples from 1421
      IPs) or both FMD virus and antibody (virological and serological samples from 255
      IPs) or antibody alone (from 44 IPs). The time taken to issue final diagnostic
      results ranged from a few hours in cases in which positive results were obtained
      by ELISA on epithelia containing sufficient virus to be detected, to several days
      for samples containing small amounts of virus requiring amplification through
      cell culture, negative samples or samples tested for antibody. Two subsets of
      samples were analysed retrospectively by real-time reverse transcriptase-PCR (RT
      PCR); first, epithelia that were negative by both ELISA and virus isolation (VI)
      in cell culture, and secondly, samples that were negative by ELISA on epithelial
      suspension but positive by VI. There was broad agreement between the RT-PCR and
      VI/ELISA combined, except that the RT-PCR procedure did not detect a group of
      related virus isolates from Wales. These viruses had evidently evolved during the
      epidemic and had a nucleotide substitution in the RT-PCR probe site, which
      prevented them from being detected by the routine diagnostic probe. No evidence
      of FMD virus, antibody or nucleic acid was found in approximately 23 per cent
      (390 of 1730) of IPs from which samples were received, suggesting that the
      incidence of FMD during the outbreak may have been over-reported.

PMID- 16980523
TI  - Control of rabies in Jaipur, India, by the sterilisation and vaccination of
      neighbourhood dogs.
AB  - A programme to sterilise and vaccinate neighbourhood dogs against rabies was
      established in Jaipur, India. Neighbourhood dogs were captured humanely,
      sterilised surgically, vaccinated against rabies and, when they had recovered,
      released where they had been caught. Between November 1994 and December 2002,
      24,986 dogs were treated in this way. Direct observational surveys of the local
      dog population indicated that 65 per cent of the females were sterilised and
      vaccinated, and that the population declined by 28 per cent. The records of human
      cases of rabies seen in the main government hospital of the city between January
      1992 and December 2002 showed that the number of cases had declined to zero in
      the programme area but increased in other areas.

PMID- 16980525
TI  - Ocular complications of barren brome exposure in a suckler herd.

PMID- 16980524
TI  - Lameness and fertility of sows and gilts in randomly selected loose-housed herds
      in Finland.
AB  - The prevalence of lameness among 646 sows and gilts in 21 selected herds was
      determined; 8.8 per cent of the animals were lame and the most common clinical
      diagnoses were osteochondrosis, infected skin lesions and claw lesions. The lame
      animals had higher serum concentrations of haptoglobin and C-reactive protein
      than the sound animals. Animals housed on slatted floors had twice the odds of
      being lame and 3.7 times the odds of being severely lame than animals housed on
      solid floors. Yorkshire pigs had 2.7 times the odds of being lame than Landrace
      or crossbred animals. Higher parity and the use of roughage decreased the odds of
      the sows not becoming pregnant; however, lameness was not a risk factor for non
      pregnancy.

PMID- 16980526
TI  - First report of Helicobacter pullorum in the faeces of a diarrhoeic psittacine
      bird (Psephotus haematogaster).

PMID- 16980527
TI  - Ophidian paramyxovirus in Brazilian vipers (Bothrops alternatus).

PMID- 16980528
TI  - Hazardous Waste Regulations 2005.

PMID- 16980530
TI  - Spread of bovine TB as a result of restocking.

PMID- 16980531
TI  - The validation of a novel activity monitor in the measurement of posture and
      motion during everyday activities.
AB  - BACKGROUND: Accurate measurement of physical activity patterns can be used to
      identify sedentary behaviour and may facilitate interventions aimed at reducing
      inactivity. OBJECTIVE: To evaluate the activPAL physical activity monitor as a
      measure of posture and motion in everyday activities using observational analysis
      as the criterion standard. METHODS: Wearing three activPAL monitors, 10 healthy
      participants performed a range of randomly assigned everyday tasks incorporating
      walking, standing and sitting. Each trial was captured on a digital camera and
      the recordings were synchronised with the activPAL. The time spent in different
      postures was visually classified and this was compared with the activPAL output.
      RESULTS: Intraclass correlation coefficients (ICC 2,1) for interdevice
      reliability ranged from 0.79 to 0.99. Using the Bland and Altman method, the mean
      percentage difference between the activPAL monitor and observation for total time
      spent sitting was 0.19% (limits of agreement -0.68% to 1.06%) and for total time
      spent upright was -0.27% (limits of agreement -1.38% to 0.84%). The mean
      difference for total time spent standing was 1.4% (limits of agreement -6.2% to
      9.1%) and for total time spent walking was -2.0% (limits of agreement -16.1% to
      12.1%). A second-by-second analysis between observer and monitor found an overall
      agreement of 95.9%. CONCLUSION: The activPAL activity monitor is a valid and
      reliable measure of posture and motion during everyday physical activities.

PMID- 16980532
TI  - Spontaneous tetraplegia during weight training.
AB  - A case of tetraplegia due to weight training is presented. Emergency surgery
      revealed a huge C5/6 disc sequestration trapped within the canal by the posterior
      longitudinal ligament. The disc was removed and C5-C7 were fused using an iliac
      crest tricortical graft and stabilised. The patient made a good recovery and
      returned to sporting activity.

PMID- 16980533
TI  - Results of arthroscopic debridement for osteochondritis dissecans of the elbow.
AB  - OBJECTIVE: To determine the clinical outcome of arthroscopic debridement for
      osteochondritis dissecans of the elbow. METHODS: A prospective cohort study was
      started in 2000; between 2000 and 2005, 15 patients (six male, nine female, mean
      age 28 years (range 16-49)) were treated for osteochondritis dissecans of the
      elbow with arthroscopic debridement. The lesion was graded during surgery using
      the classification of Baumgarten. The dominant side was operated on in seven of
      15 patients, and all patients were involved in a sport in which the elbow is used
      extensively. Elbow function was assessed before and after surgery using the
      modified Andrews elbow scoring system (MAESS); pain was scored on a visual
      analogue scale (0, no pain; 10, severe pain). Evaluation was performed an average
      of 45 (range 18-59) months after surgery. Statistical analysis (Student's t test)
      was carried out using SPSS statistical software. p<0.005 was considered
      significant. RESULTS: There were no complications. The range of motion did not
      improve significantly. The mean MAESS score improved from 65.5 (poor) before
      surgery to 90.8 (excellent) after (p<0.001). The mean level of pain at rest
      decreased from 3 to 1, and the level of pain after provocation decreased from 7
      to 2 (p<0.001). All patients were able to return to work 3 months after surgery,
      and 80% were able to resume their pre-injury level of sport activity. CONCLUSION:
      The clinical outcome after arthroscopic debridement for osteochondritis dissecans
      of the elbow shows good results, with pain relief during activities of daily
      living and sport. The function of the elbow, as reflected by the MAESS score,
      improved from poor to excellent. All patients in this series will be reviewed
      after 5 years to determine long-term results.

PMID- 16980534
TI  - Use of the one-legged hyperextension test and magnetic resonance imaging in the
      diagnosis of active spondylolysis.
AB  - BACKGROUND: Active spondylolysis is an acquired lesion in the pars
      interarticularis and is a common cause of low back pain in the young athlete.
      OBJECTIVES: To evaluate whether the one-legged hyperextension test can assist in
      the clinical detection of active spondylolysis and to determine whether magnetic
      resonance imaging (MRI) is equivalent to the clinical gold standard of bone
      scintigraphy and computed tomography in the radiological diagnosis of this
      condition. METHODS: A prospective cohort design was used. Young active subjects
      with low back pain were recruited. Outcome measures included clinical assessment
      (one-legged hyperextension test) and radiological investigations including bone
      scintigraphy (with single photon emission computed tomography (SPECT)) and MRI.
      Computed tomography was performed if bone scintigraphy was positive. RESULTS:
      Seventy one subjects were recruited. Fifty pars interarticulares in 39 subjects
      (55%) had evidence of active spondylolysis as defined by bone scintigraphy (with
      SPECT). Of these, 19 pars interarticulares in 14 subjects showed a fracture on
      computed tomography. The one-legged hyperextension test was neither sensitive nor
      specific for the detection of active spondylolysis. MRI revealed bone stress in
      40 of the 50 pars interarticulares in which it was detected by bone scintigraphy
      (with SPECT), indicating reduced sensitivity in detecting bone stress compared
      with bone scintigraphy (p = 0.001). Conversely, MRI revealed 18 of the 19 pars
      interarticularis fractures detected by computed tomography, indicating
      concordance between imaging modalities (p = 0.345). There was a significant
      difference between MRI and the combination of bone scintigraphy (with
      SPECT)/computed tomography in the radiological visualisation of active
      spondylolysis (p = 0.002). CONCLUSIONS: These results suggest that there is a
      high rate of active spondylolysis in active athletes with low back pain. The one
      legged hyperextension test is not useful in detecting active spondylolysis and
      should not be relied on to exclude the diagnosis. MRI is inferior to bone
      scintigraphy (with SPECT)/computed tomography. Bone scintigraphy (with SPECT)
      should remain the first-line investigation of active athletes with low back pain
      followed by limited computed tomography if bone scintigraphy is positive.

PMID- 16980535
TI  - A multidisciplinary selection model for youth soccer: the Ghent Youth Soccer
      Project.
AB  - OBJECTIVES: To determine the relationships between physical and performance
      characteristics and level of skill in youth soccer players aged 12-16 years.
      METHODS: Anthropometry, maturity status, functional and sport-specific parameters
      were assessed in elite, sub-elite, and non-elite youth players in four age
      groups: U13 (n = 117), U14 (n = 136), U15 (n = 138) and U16 (n = 99). RESULTS:
      Multivariate analyses of covariance by age group with maturity status as the
      covariate showed that elite players scored better than the non-elite players on
      strength, flexibility, speed, aerobic endurance, anaerobic capacity and several
      technical skills (p<0.05). Stepwise discriminant analyses showed that running
      speed and technical skills were the most important characteristics in U13 and U14
      players, while cardiorespiratory endurance was more important in U15 and U16
      players. The results suggest that discriminating characteristics change with
      competitive age levels. CONCLUSIONS: Characteristics that discriminate youth
      soccer players vary by age group. Talent identification models should thus be
      dynamic and provide opportunities for changing parameters in a long-term
      developmental context.

PMID- 16980536
TI  - Rupture of a flexor pollicis longus repair in a body builder through the use of
      an electronic muscle stimulator.
AB  - Involvement of tendons in hand lacerations is common, and immediate treatment
      involves exploration and primary repair. A programme of protected rehabilitation
      to allow healing and prevent rupture must follow. An unusual case is reported of
      tendon rupture in a body builder caused by use of an electronic muscle
      stimulator. Body builders should be warned about this mode of rupture, which has
      not been previously reported, during their rehabilitation.

PMID- 16980537
TI  - Non-random fluctuations in power output during self-paced exercise.
AB  - OBJECTIVES: To analyse the power output measured during a self-paced 20-km
      cycling time trial, during which power output was free to vary, in order to
      assess the level and characteristics of the variability in power output that
      occurred during the exercise bout. METHODS: Eleven well-trained cyclists
      performed a 20-km cycling time trial, during which power output was sampled every
      200 m. Power spectrum analysis was performed on the power output data, and a
      fractal dimension was calculated for each trial using the Higuchi method.
      RESULTS: In all subjects, power output was maintained throughout the trial until
      the final kilometre, when it increased significantly, indicating the presence of
      a global pacing strategy. The power spectrum revealed the presence of 1/f-like
      scaling of power output and multiple frequency peaks during each trial, with the
      values of the frequency peaks changing over the course of the trial. The fractal
      dimension (D-score) was similar for all subjects over the 20-km trial and ranged
      between 1.5 and 1.9. CONCLUSIONS: The presence of an end spurt in all subjects,
      1/f-like scaling and multiple frequency peaks in the power output data indicate
      that the measured oscillations in power output during cycling exercise activity
      may not be system noise, but may rather be associated with system control
      mechanisms that are similar in different individuals.

PMID- 16980538
TI  - The chromatin assembly factor subunit FASCIATA1 is involved in homologous
      recombination in plants.
AB  - DNA replication in cycling eukaryotic cells necessitates the reestablishment of
      chromatin after nucleosome redistribution from the parental to the two daughter
      DNA strands. Chromatin assembly factor 1 (CAF-1), a heterotrimeric complex
      consisting of three subunits (p150/p60/p48), is one of the replication-coupled
      assembly factors involved in the reconstitution of S-phase chromatin. CAF-1 is
      required in vitro for nucleosome assembly onto newly replicated chromatin in
      human cells and Arabidopsis thaliana, and defects in yeast (Saccharomyces
      cerevisiae) affect DNA damage repair processes, predominantly those involved in
      genome stability. However, in vivo chromatin defects of caf-1 mutants in higher
      eukaryotes are poorly characterized. Here, we show that fasciata1-4 (fas1-4), a
      new allele of the Arabidopsis fas1 mutant defective in the p150 subunit of CAF-1,
      has a severe developmental phenotype, reduced heterochromatin content, and a more
      open conformation of euchromatin. Most importantly, homologous recombination
      (HR), a process involved in maintaining genome stability, is increased
      dramatically in fas1-4, as indicated by a 96-fold stimulation of intrachromosomal
      HR. Together with the open conformation of chromatin and the nearly normal
      expression levels of HR genes in the mutant, this result suggests that chromatin
      is a major factor restricting HR in plants.

PMID- 16980539
TI  - Structural and functional insights into the chloroplast ATP-dependent Clp
      protease in Arabidopsis.
AB  - In contrast with the model Escherichia coli Clp protease, the ATP-dependent Clp
      protease in higher plants has a remarkably diverse proteolytic core consisting of
      multiple ClpP and ClpR paralogs, presumably arranged within a dual heptameric
      ring structure. Using antisense lines for the nucleus-encoded ClpP subunit,
      ClpP6, we show that the Arabidopsis thaliana Clp protease is vital for
      chloroplast development and function. Repression of ClpP6 produced a proportional
      decrease in the Clp proteolytic core, causing a chlorotic phenotype in young
      leaves that lessened upon maturity. Structural analysis of the proteolytic core
      revealed two distinct subcomplexes that likely correspond to single heptameric
      rings, one containing the ClpP1 and ClpR1-4 proteins, the other containing ClpP3
      6. Proteomic analysis revealed several stromal proteins more abundant in clpP6
      antisense lines, suggesting that some are substrates for the Clp protease. A
      proteolytic assay developed for intact chloroplasts identified potential
      substrates for the stromal Clp protease in higher plants, most of which were more
      abundant in young Arabidopsis leaves, consistent with the severity of the
      chlorotic phenotype observed in the clpP6 antisense lines. The identified
      substrates all function in more general housekeeping roles such as plastid
      protein synthesis, folding, and quality control, rather than in metabolic
      activities such as photosynthesis.

PMID- 16980540
TI  - Rapid transcriptome changes induced by cytosolic Ca2+ transients reveal ABRE
      related sequences as Ca2+-responsive cis elements in Arabidopsis.
AB  - The regulation of gene expression by cellular calcium is crucial for plant
      defense against biotic and abiotic stresses. However, the number of genes known
      to respond to specific transient calcium signals is limited, and as yet there is
      no definition of a calcium-responsive cis element in plants. Here, we generated
      specific cytosolic calcium transients in intact Arabidopsis thaliana seedlings
      and linked them to early transcriptome changes, followed by bioinformatic
      analysis of the responsive genes. A cytosolic calcium transient induced by
      calmodulin antagonists and blocked by lanthanides was characterized using
      aequorin-based luminometry and photon imaging. Analysis of transcriptome changes
      revealed 230 calcium-responsive genes, of which 162 were upregulated and 68 were
      downregulated. These include known early stress-responsive genes as well as genes
      of unknown function. Analysis of their upstream regions revealed, exclusively in
      the upregulated genes, a highly significant occurrence of a consensus sequence (P
      < 10(-13)) comprising two abscisic acid-specific cis elements: the abscisic acid
      responsive element (ABRE; CACGTG[T/C/G]) and its coupling element
      ([C/A]ACGCG[T/C/G]) [corrected] Finally, we show that a tetramer of the ABRE cis
      element is sufficient to confer transcriptional activation in response to
      cytosolic Ca(2+) transients. Thus, at least for some specific Ca(2+) transients
      and motif combinations, ABREs function as Ca(2+)-responsive cis elements.

PMID- 16980541
TI  - A transcription factor-binding domain of the coactivator CBP is essential for
      long-term memory and the expression of specific target genes.
AB  - Transcriptional activation is a key process required for long-term memory
      formation. Recently, the transcriptional coactivator CREB-binding protein (CBP)
      was shown to be critical for hippocampus-dependent long-term memory and
      hippocampal synaptic plasticity. As a coactivator with intrinsic histone
      acetyltransferase activity, CBP interacts with numerous transcription factors and
      contains multiple functional domains. Currently, it is not known which
      transcription factor-binding domain of CBP is essential for memory storage. Using
      mice that carry inactivating mutations in the CREB-binding (KIX) domain of the
      coactivator CBP (CBPKIX/KIX mice), we show that the KIX domain is required for
      long-term memory storage. These results are the first to identify an in vivo
      function for the KIX domain of CBP in the brain, and they suggest that KIX
      interacting transcription factors recruit CBP histone acetyltransferase activity
      during long-term memory storage. One such KIX-interacting factor is the
      transcription factor CREB. Using quantitative real-time RT-PCR, we find that the
      expression of specific CREB target genes is reduced in the hippocampi of
      CBPKIX/KIX mice during memory consolidation. The recruitment of the
      transcriptional coactivator CBP via the KIX domain thus imparts target gene
      dependent selectivity to CREB-driven transcriptional regulation, thereby
      activating genes required for the long-term storage of hippocampus-dependent
      memory.

PMID- 16980542
TI  - Roles for Drosophila mushroom body neurons in olfactory learning and memory.
AB  - Olfactory learning assays in Drosophila have revealed that distinct brain
      structures known as mushroom bodies (MBs) are critical for the associative
      learning and memory of olfactory stimuli. However, the precise roles of the
      different neurons comprising the MBs are still under debate. The confusion
      surrounding the roles of the different neurons may be due, in part, to the use of
      different odors as conditioned stimuli in previous studies. We investigated the
      requirements for the different MB neurons, specifically the alpha/beta versus the
      gamma neurons, and whether olfactory learning is supported by different subsets
      of MB neurons irrespective of the odors used as conditioned stimuli. We expressed
      the rutabaga (rut)-encoded adenylyl cyclase in either the gamma or alpha/beta
      neurons and examined the effects on restoring olfactory associative learning and
      memory of rut mutant flies. We also expressed a temperature-sensitive shibire
      (shi) transgene in these neuron sets and examined the effects of disrupting
      synaptic vesicle recycling on Drosophila olfactory learning. Our results indicate
      that although we did not detect odor-pair-specific learning using GAL4 drivers
      that primarily express in gamma neurons, expression of the transgenes in a subset
      of alpha/beta neurons resulted in both odor-pair-specific rescue of the rut
      defect as well as odor-pair-specific disruption of learning using shi(ts1).

PMID- 16980543
TI  - Early boost and slow consolidation in motor skill learning.
AB  - Motorskill learning is a dynamic process that continues covertly after training
      has ended and eventually leads to delayed increments in performance. Current
      theories suggest that this off-line improvement takes time and appears only after
      several hours. Here we show an early transient and short-lived boost in
      performance, emerging as early as 5-30 min after training but no longer observed
      4 h later. This early boost is predictive of the performance achieved 48 h later,
      suggesting its functional relevance for memory processes.

PMID- 16980544
TI  - Distinct roles for medial temporal lobe structures in memory for objects and
      their locations.
AB  - The ability to learn and retain novel information depends on a system of
      structures in the medial temporal lobe (MTL) including the hippocampus and the
      surrounding entorhinal, perirhinal, and parahippocampal cortices. Damage to these
      structures produces profound memory deficits; however, the unique contribution to
      memory of each of these structures remains unclear. Here we have used functional
      magnetic resonance imaging (fMRI) to determine whether the perirhinal and
      parahippocampal cortices show differential memory-related activity. Based on the
      distinct patterns of cortical input to these two areas, we reasoned that these
      structures might show differential activity for spatial and object recognition
      memory. In each of 11 subjects, we found that the perirhinal cortex was active
      during both spatial and object memory encoding, while the anterior
      parahippocampal cortex was active only during spatial encoding. These data
      support the idea that MTL structures make distinct contributions to recognition
      memory performance.

PMID- 16980545
TI  - Two mutations preventing PDZ-protein interactions of GluR1 have opposite effects
      on synaptic plasticity.
AB  - The regulated trafficking of GluR1 contributes significantly to synaptic
      plasticity, but studies addressing the function of the GluR1 C-terminal PDZ
      ligand domain in this process have produced conflicting results. Here, we resolve
      this conflict by showing that apparently similar C-terminal mutations of the
      GluR1 PDZ-ligand domain result in opposite physiological phenotypes during
      activity- and CamKII-induced synaptic plasticity.

PMID- 16980546
TI  - Single-item memory, associative memory, and the human hippocampus.
AB  - We tested recognition memory for items and associations in memory-impaired
      patients with bilateral lesions thought to be limited to the hippocampal region.
      In Experiment 1 (Combined memory test), participants studied words and then took
      a memory test in which studied words, new words, studied word pairs, and
      recombined word pairs were presented in a mixed order. In Experiment 2 (Separated
      memory test), participants studied single words and then took a memory test
      involving studied word and new words. In a separate test, they studied word pairs
      and then took a memory test involving studied word pairs and recombined word
      pairs. In both experiments, patients were impaired at memory for single items as
      well as memory for associations, suggesting that the hippocampus is important for
      both of these memory functions. In Experiment 1, patients appeared to be more
      impaired at associative memory than item memory. In Experiment 2, patients were
      similarly impaired at associative memory and item memory. These different
      findings are considered, including the fact that in Experiment 1 the results
      depended on the fact that controls produced unexpectedly low false-alarm rates to
      recombined pairs. We discuss single-item and associative memory from the
      perspective that the hippocampus and adjacent cortex work cooperatively to signal
      recognition and that simple dichotomies do not adequately describe the division
      of labor within the medial temporal lobe.

PMID- 16980547
TI  - Learning in the absence of experience-dependent regulation of NMDAR composition.
AB  - Olfactory discrimination (OD) learning consists of two phases: an initial N
      methyl-D-aspartate (NMDA) receptor-sensitive rule-learning phase, followed by an
      NMDA receptor (NMDAR)-insensitive pair-learning phase. The rule-learning phase is
      accompanied by changes in the composition and function of NMDARs at synapses in
      the piriform cortex, resulting in a high level of the NR2a subunit relative to
      NR2b. Here we show that the learning-induced changes in NMDAR composition in the
      adult piriform cortex are due to a decrease in the level of the NR2b subunit
      protein, rather than an increase in the level of NR2a. Chronic administration of
      an NMDAR open channel blocker during training delays OD learning and blocks
      learning-induced changes in NMDAR subunit composition. However, the animals still
      learn the OD task. Our data demonstrate that learning can occur in the absence of
      activity-dependent regulation of NMDAR composition, suggesting differences in the
      mechanism for long-term maintenance of NMDAR-dependent and NMDAR-independent
      learning.

PMID- 16980548
TI  - Behavioral interference and C/EBPbeta expression in the insular-cortex reveal a
      prolonged time period for taste memory consolidation.
AB  - Memory consolidation is defined as the time window during which the memory trace
      is susceptible to behavioral, electrical, or pharmacological interventions. Here,
      we presented rats with two novel tastes at consecutive time intervals. Clear
      interference was evident when a novel taste formed the second taste input
      whereby, surprisingly, the time window for interference was found to last more
      than 10 h. In addition, we detected an increase of C/EBPbeta protein expression
      in the gustatory cortex 18 h after novel taste learning. This modulation was
      attenuated by a subsequent novel taste. Our findings reveal temporal constraints
      and a lingering nature of taste memory consolidation.

PMID- 16980549
TI  - Role of centrifugal projections to the olfactory bulb in olfactory processing.
AB  - While there is evidence that feedback projections from cortical and
      neuromodulatory structures to the olfactory bulb are crucial for maintaining the
      oscillatory dynamics of olfactory bulb processing, it is not clear how changes in
      dynamics are related to odor perception. Using electrical lesions of the
      olfactory peduncle, sparing output from the olfactory bulb while decreasing
      feedback inputs to the olfactory bulb, we demonstrate here a role for feedback
      inputs to the olfactory bulb in the formation of odor-reward associations, but
      not for maintaining primary bulbar odor representations, as reflected by
      spontaneous odor discrimination.

PMID- 16980550
TI  - Carbon monoxide and bilirubin: potential therapies for pulmonary/vascular injury
      and disease.
AB  - Heme oxygenase (HO)-1, an inducible, low-molecular-weight stress protein, confers
      cellular and tissue protection in multiple models of injury and disease,
      including oxidative or inflammatory lung injury, ischemia/reperfusion (I/R)
      injuries, and vascular injury/disease. The tissue protection provided by HO-1
      potentially relates to the endogenous production of the end products of its
      enzymatic activity: namely, biliverdin (BV)/bilirubin (BR), carbon monoxide (CO),
      and iron. Of these, CO and BV/BR show promise as possible therapeutic agents when
      applied exogenously in models of lung or vascular injury. CO activates
      intracellular signaling pathways that involve soluble guanylate cyclase and/or
      p38 mitogen-activated protein kinase. Although toxic at elevated concentrations,
      low concentrations of CO can confer antiinflammatory, antiapoptotic,
      antiproliferative, and vasodilatory effects. BV and BR are natural antioxidants
      that can provide protection against oxidative stress in cell culture and in
      plasma. Application of BV or BR protects against I/R injury in several organ
      models. Recent evidence has also demonstrated antiinflammatory and
      antiproliferative properties of these pigments. To date, evidence has accumulated
      for salutary effects of CO, BV, and/or BR in lung/vascular injury models, as well
      as in models of transplant-associated I/R injury. Thus, the exogenous application
      of HO end products may provide an alternative to pharmacologic or gene therapy
      approaches to harness the therapeutic potential of HO-1.

PMID- 16980551
TI  - The role of heme oxygenase-1 in pulmonary disease.
AB  - Heme oxygenase (HO)-1, the inducible isoform of heme oxygenase, is a
      cytoprotective enzyme that plays a central role in the defense against oxidative
      and inflammatory insults in the lung. HO-1 catalyzes the degradation of heme, a
      potent oxidant, into biliverdin, iron, and carbon monoxide (CO). These downstream
      products of heme catabolism have recently been found to mediate the antioxidant,
      antiapoptotic, antiproliferative, vasodilatory, and anti-inflammatory properties
      of HO-1. Although absence of HO-1 is rare in humans, a number of HO-1 promoter
      polymorphisms have been identified that may influence HO-1 expression in vivo and
      lead to disease states. This review will summarize studies that implicate HO-1
      and heme metabolites in the pathophysiology of pulmonary disease and discuss
      recent advances in the therapeutic applications of HO-1.

PMID- 16980552
TI  - Modulation of glutaredoxin-1 expression in a mouse model of allergic airway
      disease.
AB  - Glutaredoxins (GRX) are antioxidant enzymes that preferentially catalyze the
      reduction of protein-glutathione mixed disulfides. The formation of mixed
      disulfides with GSH is known as S-glutathionylation, a post-translational
      modification that is emerging as an important mode of redox signaling. Since
      asthma is a disease that is associated with increased oxidative stress and
      altered antioxidant defenses, we investigated the expression of GRX in a murine
      model of allergic airway disease. Sensitization and challenge of C57BL/6 mice
      with ovalbumin resulted in increased expression of GRX1 mRNA, as well as
      increased amounts of GRX1 protein and total GRX activity in the lung. Because
      GRX1 expression is prominent in bronchial epithelium, we isolated primary
      epithelial cells from mouse trachea to investigate the presence of GRX. Primary
      tracheal epithelial cells were found to express both GRX1 and 2 mRNA and
      detectable GRX activity. Treatment with IFN-gamma increased the expression of
      GRX1 and overall GRX activity, resulting in attenuation of protein S
      glutathionylation. In contrast, TGF-beta1 caused decreased GRX1 expression and
      overall GRX activity, leading to markedly enhanced protein S-glutathionylation.
      GRX1 joins the cadre of antioxidant defenses known to be modulated during
      allergic airway inflammation.

PMID- 16980553
TI  - Pleiotropic beta-agonist-promoted receptor conformations and signals independent
      of intrinsic activity.
AB  - Beta-agonists used for treatment of obstructive lung disease have a variety of
      different structures but are typically classified by their intrinsic activities
      for stimulation of cAMP, and predictions are made concerning other downstream
      signals based on such a classification. We generated modified beta(2)-adrenergic
      receptors with insertions of energy donor and acceptor moieties to monitor
      agonist-promoted conformational changes of the receptor using intramolecular
      bioluminescence resonance energy transfer in live cells. These studies suggested
      unique conformations stabilized by various agonists that were not based on their
      classic intrinsic activities. To address the cellular consequences of these
      differences, G(s)-coupling, G(i)-coupling (p44/p42 activation), G protein-coupled
      receptor kinase-mediated receptor phosphorylation, internalization, and down
      regulation were assessed in response to isoproterenol, albuterol, terbutaline,
      metaproterenol, salmeterol, formoterol, and fenoterol. In virtually every case,
      agonists did not maintain the classic rank order, indicating that distinct
      signaling is evoked by beta-agonists of different structures, which is unrelated
      to intrinsic activity. The extensive pleiotropy of agonist responses shown here
      suggests that classification of agonists by cAMP-based intrinsic activity is
      inadequate as it pertains to other intracellular events and that it may be
      possible to engineer a beta-agonist that stabilizes conformations that evoke an
      ideal portfolio of signals for therapeutic purposes.

PMID- 16980554
TI  - Nitric oxide promotes airway epithelial wound repair through enhanced activation
      of MMP-9.
AB  - The airway epithelium provides a protective barrier against inhaled environmental
      toxins and microorganisms, and epithelial injury initiates a number of processes
      to restore its barrier integrity, including activation of matrix
      metalloproteinases such as MMP-9 (92-kD gelatinase B). Airway epithelial cells
      continuously produce nitric oxide (NO), which has been linked to cell migration
      and MMP-9 regulation in several cell types, but the importance of epithelial NO
      in mediating airway epithelial repair or MMP-9 activation is unknown. Using
      primary or immortalized human bronchial epithelial cells, we demonstrate that low
      concentrations of NO promote epithelial cell migration and wound repair in an in
      vitro wound assay, which was associated with increased localized expression and
      activation of MMP-9. In addition, in HBE1 cells that were stably transfected with
      inducible NOS (NOS2), to mimic constitutive epithelial NOS2 expression in vivo,
      NOS inhibition decreased epithelial wound repair and MMP-9 expression. The
      stimulatory effects of NO on epithelial wound repair and MMP-9 expression were
      dependent on cGMP-mediated pathways and were inhibited by 1H-[1,2,4]oxadiazolo
      [4,3-a]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylyl cyclase.
      Inhibition of cGMP-dependent protein kinase (PKG) attenuated NO-mediated
      epithelial wound closure, but did not affect MMP-9 expression. However,
      pharmacologic MMP inhibition and siRNA knockdown of MMP-9 expression demonstrated
      the contribution of MMP-9 to NO-mediated wound closure. Overall, our results
      demonstrate that NOS2-derived NO contributes to airway epithelial repair by both
      PKG-dependent and -independent mechanisms, and involves NO-dependent expression
      and activation of MMP-9.

PMID- 16980555
TI  - IL-13 and epidermal growth factor receptor have critical but distinct roles in
      epithelial cell mucin production.
AB  - Overproduction of mucus is a central feature of asthma. The cytokine, IL-13,
      epidermal growth factor receptor (EGFR), and transcription factor, FOXA2, have
      each been implicated in mucus production, but the mechanistic relationships
      between these molecules are not yet well understood. To address this, we
      established a primary normal human bronchial epithelial cell culture system with
      IL-13-induced mucus production and gene transcript expression changes similar to
      those seen in vivo in mice. IL-13 did not stimulate release of the EGFR ligand,
      transforming growth factor (TGF)-alpha. However, there was constitutive release
      of TGF-alpha from normal human bronchial epithelial cells, and inhibition of TGF
      alpha or EGFR reduced both constitutive and IL-13-induced mucin production.
      Microarray analysis revealed that IL-13 and the EGFR pathway appear to have
      almost completely independent effects on transcript expression. IL-13 induced a
      relatively small set of transcripts, including several novel transcripts that
      might play a role in pathogenesis of allergic airway disease. In contrast, EGFR
      activity had extensive effects, including altered expression of many transcripts
      associated with cell metabolism, survival, transcription, and differentiation.
      One of the few common effects of IL-13 and EGFR signaling was decreased
      expression of FOXA2, which is known to prevent mucus production. We conclude that
      the IL-13 and EGFR pathways make critical but quite distinct contributions to
      gene regulation in airway epithelial cells, and that both pathways affect
      expression of the key transcription factor, FOXA2, a known regulator of mucus
      production.

PMID- 16980556
TI  - Salmeterol stimulation dissociates beta2-adrenergic receptor phosphorylation and
      internalization.
AB  - Salmeterol is a long-acting beta(2)-adrenergic receptor (beta(2)AR) agonist
      commonly used in the treatment of asthma and chronic obstructive pulmonary
      disease. It differs from other beta-agonists in that it has a very low intrinisic
      efficacy, especially when compared with the other available long-acting beta
      agonist, formoterol. Receptor desensitization and down-regulation has been
      described with the chronic use of beta-agonists. This effect may not be the same
      with all beta-agonists and may be related to their stabilization of altered
      receptor states. The extreme hydrophobicity and high-affinity quasi-irreversible
      binding of salmeterol have rendered studies examining the mechanisms by which it
      mediates receptor desensitization, down-regulation, and internalization
      difficult. We determined the capacity of salmeterol to induce beta(2)AR
      endocytosis, G protein-coupled receptor kinase (GRK)-site phosphorylation,
      degradation, and beta-arrestin2 translocation in HEK293 cells as compared with
      other agonists of varying intrinsic efficacies. Despite stimulating GRK-mediated
      phosphorylation of Ser355,356 after 30 min and 18 h to an extent similar to that
      observed with agonists of high intrinsic efficacy, such as epinephrine and
      formoterol, salmeterol did not induce significant beta(2)AR internalization or
      degradation and was incapable of stimulating the translocation of enhanced green
      fluorescent protein-beta-arrestin2 chimera (EGFP-beta-arrestin2) to the cell
      surface. Salmeterol-induced receptor endocytosis was rescued, at least in part,
      by the overexpression of EGFP-beta-arrestin2. Our data indicate that salmeterol
      binding induces an active receptor state that is unable to recruit beta-arrestin
      or undergo significant endocytosis or degradation despite stimulating
      considerable GRK-site phosphorylation. Defects in these components of salmeterol
      induced receptor desensitization may be important determinants of its sustained
      bronchodilation with chronic use.

PMID- 16980557
TI  - Beryllium-induced TNF-alpha production is transcription-dependent in chronic
      beryllium disease.
AB  - Beryllium (Be)-antigen presentation to Be-specific CD4(+) T cells from the lungs
      of patients with chronic beryllium disease (CBD) results in T cell proliferation
      and TNF-alpha secretion. We tested the hypothesis that Be-induced, CBD
      bronchoalveolar lavage (BAL) T cell, transcription-dependent, TNF-alpha secretion
      was accompanied by specific transcription factor upregulation. After 6 h of Be
      stimulation, CBD BAL cells produced a median of 883 pg/ml TNF-alpha (range, 608
      1,275 pg/ml) versus 198 pg/ml (range, 116-245 pg/ml) by unstimulated cells. After
      12 h CBD BAL cells produced a median of 2,963 pg/ml (range, 99-9,424 pg/ml) TNF
      alpha versus 55 pg/ml (range, 0-454) by unstimulated cells. Using real-time RT
      PCR, Be-stimulated TNF-alpha production at 6 h was preceded by a 5-fold increase
      in TNF-alpha pre-mRNA copy number:beta-actin copy number (Be median ratio 0.21;
      unstimulated median ratio 0.04). The median ratio of mature TNF-alpha mRNA:beta
      actin mRNA was upregulated 1.4-fold (Be median ratio 0.17; unstimulated median
      ratio 0.12). Be exposure in the presence of the transcription inhibitor
      pentoxifylline (PTX) decreased CBD BAL cell TNF-alpha pre-mRNA levels > 60%,
      whereas treatment with the mRNA splicing inhibitor 2-aminopurine (2AP) decreased
      levels 40% relative to Be exposure alone. PTX treatment decreased mature TNF
      alpha mRNA levels 50% while 2AP decreased levels > 80%, relative to Be exposure
      alone. Beryllium exposure specifically upregulated transcription factors AP-1 and
      NF-kappaB. The data suggest that Be exposure induces transcription-dependent TNF
      alpha production, potentially due to upregulation of specific transcription
      factors.

PMID- 16980558
TI  - Green light adjusts the plastid transcriptome during early photomorphogenic
      development.
AB  - During the transition from darkness to light, a suite of light sensors guides
      gene expression, biochemistry, and morphology to optimize acclimation to the new
      environment. Ultraviolet, blue, red, and far-red light all have demonstrated
      roles in modulating light responses, such as changes in gene expression and
      suppression of stem growth rate. However, green wavebands induce stem growth
      elongation, a response not likely mediated by known photosensors. In this study,
      etiolated Arabidopsis (Arabidopsis thaliana) seedlings were treated with a short,
      dim, single pulse of green light comparable in fluence and duration to that
      previously shown to excite robust stem elongation. Genome microarrays were then
      used to monitor coincident changes in gene expression. As anticipated,
      phytochrome A-regulated, nuclear-encoded transcripts were induced, confirming
      proper function of the sensitive phytochrome system. In addition, a suite of
      plastid-encoded transcripts decreased in abundance, including several typically
      up-regulated after phytochrome and/or cryptochrome activation. Further analyses
      using RNA gel-blot experiments demonstrated that the response is specific to
      green light, fluence dependent, and detectable within 30 min. The response obeys
      reciprocity and persists in the absence of known photosensors. Plastid transcript
      down-regulation was also observed in tobacco (Nicotiana tabacum) with similar
      temporal and fluence-response kinetics. Together, the down-regulation of plastid
      transcripts and increase in stem growth rate represent a mechanism that tempers
      progression of early commitment to the light environment, helping tailor seedling
      development during the critical process of establishment.

PMID- 16980560
TI  - Carotenoid cleavage dioxygenase (CmCCD4a) contributes to white color formation in
      chrysanthemum petals.
AB  - The white petals of chrysanthemum (Chrysanthemum morifolium Ramat.) are believed
      to contain a factor that inhibits the accumulation of carotenoids. To find this
      factor, we performed polymerase chain reaction-Select subtraction screening and
      obtained a clone expressed differentially in white and yellow petals. The deduced
      amino acid sequence of the protein (designated CmCCD4a) encoded by the clone was
      highly homologous to the sequence of carotenoid cleavage dioxygenase. All the
      white-flowered chrysanthemum cultivars tested showed high levels of CmCCD4a
      transcript in their petals, whereas most of the yellow-flowered cultivars showed
      extremely low levels. Expression of CmCCD4a was strictly limited to flower petals
      and was not detected in other organs, such as the root, stem, or leaf. White
      petals turned yellow after the RNAi construct of CmCCD4a was introduced. These
      results indicate that in white petals of chrysanthemums, carotenoids are
      synthesized but are subsequently degraded into colorless compounds, which results
      in the white color.

PMID- 16980559
TI  - Branching genes are conserved across species. Genes controlling a novel signal in
      pea are coregulated by other long-distance signals.
AB  - Physiological and genetic studies with the ramosus (rms) mutants in garden pea
      (Pisum sativum) and more axillary shoots (max) mutants in Arabidopsis
      (Arabidopsis thaliana) have shown that shoot branching is regulated by a network
      of long-distance signals. Orthologous genes RMS1 and MAX4 control the synthesis
      of a novel graft-transmissible branching signal that may be a carotenoid
      derivative and acts as a branching inhibitor. In this study, we demonstrate
      further conservation of the branching control system by showing that MAX2 and
      MAX3 are orthologous to RMS4 and RMS5, respectively. This is consistent with the
      long-standing hypothesis that branching in pea is regulated by a novel long
      distance signal produced by RMS1 and RMS5 and that RMS4 is implicated in the
      response to this signal. We examine RMS5 expression and show that it is more
      highly expressed relative to RMS1, but under similar transcriptional regulation
      as RMS1. Further expression studies support the hypothesis that RMS4 functions in
      shoot and rootstock and participates in the feedback regulation of RMS1 and RMS5
      expression. This feedback involves a second novel long-distance signal that is
      lacking in rms2 mutants. RMS1 and RMS5 are also independently regulated by indole
      3-acetic acid. RMS1, rather than RMS5, appears to be a key regulator of the
      branching inhibitor. This study presents new interactions between RMS genes and
      provides further evidence toward the ongoing elucidation of a model of axillary
      bud outgrowth in pea.

PMID- 16980561
TI  - Chloroplasts as a nitric oxide cellular source. Effect of reactive nitrogen
      species on chloroplastic lipids and proteins.
AB  - Nitric oxide (NO) generation by soybean (Glycine max var. ADM 4800) chloroplasts
      was studied as an endogenous product assessed by the electron paramagnetic
      resonance spin-trapping technique. Nitrite and l-arginine (Arg) are substrates
      for enzymatic activities considered to be the possible sources of NO in plants.
      Soybean chloroplasts showed a NO production of 3.2 +/- 0.2 nmol min(-1) mg(-1)
      protein in the presence of 1 mm NaNO(2). Inhibition of photosynthetic electron
      flow by 3-(3,4-dichlorophenyl)-1,1-dimethyl urea resulted in a lower rate (1.21
      +/- 0.04 nmol min(-1) mg(-1) protein) of NO generation. Chloroplasts incubated
      with 1 mm Arg showed NO production of 0.76 +/- 0.04 nmol min(-1) mg(-1) protein
      that was not affected either by omission of Ca(2+) or by supplementation with
      Ca(2+) and calmodulin to the incubation medium. This production was inhibited
      when chloroplasts were incubated in the presence of NO synthase inhibitors
      N(omega)-nitro-l-Arg methyl ester hydrochloride and N(omega)-nitro-l-Arg. In
      vitro exposure of chloroplasts to an NO donor (250 mum S-nitrosoglutathione)
      decreased lipid radical content in membranes by 29%; however, incubation in the
      presence of 25 mum peroxynitrite (ONOO(-)) led to an increase in lipid-derived
      radicals (34%). The effect of ONOO(-) on protein oxidation was determined by
      western blotting, showing an increase in carbonyl content either in stroma or
      thylakoid proteins as compared to controls. Moreover, ONOO(-) treatment
      significantly affected both O(2) evolution and chlorophyll fluorescence in
      thylakoids. Data reported here suggest that NO is an endogenous metabolite in
      soybean chloroplasts and that reactive nitrogen species could exert either
      antioxidant or prooxidant effects on chloroplast macromolecules.

PMID- 16980562
TI  - The role of cytosolic alpha-glucan phosphorylase in maltose metabolism and the
      comparison of amylomaltase in Arabidopsis and Escherichia coli.
AB  - Transitory starch of leaves is broken down hydrolytically, making maltose the
      predominant form of carbon exported from chloroplasts at night. Maltose
      metabolism in the cytoplasm of Escherichia coli requires amylomaltase (MalQ) and
      maltodextrin phosphorylase (MalP). Possible orthologs of MalQ and MalP in the
      cytosol of Arabidopsis (Arabidopsis thaliana) were proposed as disproportionating
      enzyme (DPE2, At2g40840) and alpha-glucan phosphorylase (AtPHS2, At3g46970). In
      this article, we measured the activities of recombinant DPE2 and AtPHS2 proteins
      with various substrates; we show that maltose and a highly branched, soluble
      heteroglycan (SHG) are excellent substrates for DPE2 and propose that a SHG is
      the in vivo substrate for DPE2 and AtPHS2. In E. coli, MalQ and MalP
      preferentially use smaller maltodextrins (G(3)-G(7)) and we suggest that MalQ and
      DPE2 have similar, but nonidentical, roles in maltose metabolism. To study this,
      we complemented a MalQ(-) E. coli strain with DPE2 and found that the rescue was
      not complete. To investigate the role of AtPHS2 in maltose metabolism, we
      characterized a T-DNA insertion line of the AtPHS2 gene. The nighttime maltose
      level increased 4 times in the Atphs2-1 mutant. The comparison of maltose
      metabolism in Arabidopsis with that in E. coli and the comparison of the maltose
      level in plants lacking DPE2 or AtPHS2 indicate that an alternative route to
      metabolize the glucan residues in SHG exists. Other plant species also contain
      SHG, DPE2, and alpha-glucan phosphorylase, so this pathway for maltose metabolism
      may be widespread among plants.

PMID- 16980563
TI  - CER4 encodes an alcohol-forming fatty acyl-coenzyme A reductase involved in
      cuticular wax production in Arabidopsis.
AB  - A waxy cuticle that serves as a protective barrier against uncontrolled water
      loss and environmental damage coats the aerial surfaces of land plants. It is
      composed of a cutin polymer matrix and waxes. Cuticular waxes are complex
      mixtures of very-long-chain fatty acids and their derivatives. We report here the
      molecular cloning and characterization of CER4, a wax biosynthetic gene from
      Arabidopsis (Arabidopsis thaliana). Arabidopsis cer4 mutants exhibit major
      decreases in stem primary alcohols and wax esters, and slightly elevated levels
      of aldehydes, alkanes, secondary alcohols, and ketones. This phenotype suggested
      that CER4 encoded an alcohol-forming fatty acyl-coenzyme A reductase (FAR). We
      identified eight FAR-like genes in Arabidopsis that are highly related to an
      alcohol-forming FAR expressed in seeds of jojoba (Simmondsia chinensis).
      Molecular characterization of CER4 alleles and genomic complementation revealed
      that one of these eight genes, At4g33790, encoded the FAR required for cuticular
      wax production. Expression of CER4 cDNA in yeast (Saccharomyces cerevisiae)
      resulted in the accumulation of C24:0 and C26:0 primary alcohols. Fully
      functional green fluorescent protein-tagged CER4 protein was localized to the
      endoplasmic reticulum in yeast cells by confocal microscopy. Analysis of gene
      expression by reverse transcription-PCR indicated that CER4 was expressed in
      leaves, stems, flowers, siliques, and roots. Expression of a beta-glucuronidase
      reporter gene driven by the CER4 promoter in transgenic plants was detected in
      epidermal cells of leaves and stems, consistent with a dedicated role for CER4 in
      cuticular wax biosynthesis. CER4 was also expressed in all cell types in the
      elongation zone of young roots. These data indicate that CER4 is an alcohol
      forming FAR that has specificity for very-long-chain fatty acids and is
      responsible for the synthesis of primary alcohols in the epidermal cells of
      aerial tissues and in roots.

PMID- 16980564
TI  - Up-regulation of 1-deoxy-D-xylulose-5-phosphate synthase enhances production of
      essential oils in transgenic spike lavender.
AB  - Spike lavender (Lavandula latifolia) is an aromatic shrub cultivated worldwide
      for the production of essential oils. The major constituents of these oils are
      monoterpenes, which are obtained from isopentenyl diphosphate and dimethylallyl
      diphosphate precursors through the plastidial methylerythritol phosphate (MEP)
      pathway and/or the cytosolic mevalonate pathway. 1-Deoxy-D-xylulose-5-P synthase
      (DXS) catalyzes the first step of the MEP pathway. A cDNA coding for the
      Arabidopsis (Arabidopsis thaliana) DXS was constitutively expressed in spike
      lavender. Gas chromatography/mass spectrometry analyses revealed that transgenic
      plants accumulated significantly more essential oils compared to controls (from
      101.5% to 359.0% and from 12.2% to 74.1% yield increase compared to controls in
      leaves and flowers, respectively). T(0) transgenic plants were grown for 2 years,
      self-pollinated, and the T(1) seeds obtained. The inheritance of the DXS
      transgene was studied in the T(1) generation. The increased essential oil
      phenotype observed in the transgenic T(0) plants was maintained in the progeny
      that inherited the DXS transgene. Total chlorophyll and carotenoid content in DXS
      progenies that inherited the transgene depended on the analyzed plant, showing
      either no variation or a significant decrease in respect to their counterparts
      without the transgene. Transgenic plants had a visual phenotype similar to
      untransformed plants (controls) in terms of morphology, growth habit, flowering,
      and seed germination. Our results demonstrate that the MEP pathway contributes to
      essential oil production in spike lavender. They also demonstrate that the DXS
      enzyme plays a crucial role in monoterpene precursor biosynthesis and, thus, in
      essential oil production in spike lavender. In addition, our results provide a
      strategy to increase the essential oil production in spike lavender by metabolic
      engineering of the MEP pathway without apparent detrimental effects on plant
      development and fitness.

PMID- 16980565
TI  - Separation of Arabidopsis pollen tetrads is regulated by QUARTET1, a pectin
      methylesterase gene.
AB  - Arabidopsis (Arabidopsis thaliana) QUARTET (QRT) genes are required for pollen
      separation during normal floral development. In qrt mutants, the four products of
      microsporogenesis remain fused and pollen grains are released as tetrads. In
      Arabidopsis, tetrad analysis in qrt mutants has been used to map all five
      centromeres, easily distinguish sporophytic from gametophytic mutations, and
      accurately assess crossover interference. Using a combination of forward and
      reverse genetics, we have identified the gene responsible for the qrt1 phenotype.
      Annotation predicts that QRT1 encodes a pectin methylesterase (PME), and
      enzymatic assays of QRT1 expressed in Escherichia coli indicate that QRT1 has PME
      activity. Promoter and transcription analysis demonstrate QRT1 is expressed in
      anther tissues shortly after meiosis is complete. Unexpectedly, the QRT1 promoter
      is also active in a variety of developmentally unrelated tissues, including
      developing guard cells, the hypocotyl-root transition zone, areas of lateral root
      emergence, and floral nectaries. PMEs constitute a large gene family in
      Arabidopsis, are involved in cell wall loosening, and have been implicated in
      various aspects of floral development and pollen tube elongation. The
      identification of QRT1 as a PME contributes to our understanding of pollen
      development and may help to provide valuable genetic tools in other plant
      species.

PMID- 16980567
TI  - Localization of green fluorescent protein fusions with the seven Arabidopsis
      vacuolar sorting receptors to prevacuolar compartments in tobacco BY-2 cells.
AB  - We have previously demonstrated that vacuolar sorting receptor (VSR) proteins are
      concentrated on prevacuolar compartments (PVCs) in plant cells. PVCs in tobacco
      (Nicotiana tabacum) BY-2 cells are multivesicular bodies (MVBs) as defined by VSR
      proteins and the BP-80 reporter, where the transmembrane domain (TMD) and
      cytoplasmic tail (CT) sequences of BP-80 are sufficient and specific for correct
      targeting of the reporter to PVCs. The genome of Arabidopsis (Arabidopsis
      thaliana) contains seven VSR proteins, but little is known about their individual
      subcellular localization and function. Here, we study the subcellular
      localization of the seven Arabidopsis VSR proteins (AtVSR1-7) based on the
      previously proven hypothesis that the TMD and CT sequences correctly target
      individual VSR to its final destination in transgenic tobacco BY-2 cells. Toward
      this goal, we have generated seven chimeric constructs containing signal peptide
      (sp) linked to green fluorescent protein (GFP) and TMD/CT sequences (sp-GFP
      TMD/CT) of the seven individual AtVSR. Transgenic tobacco BY-2 cell lines
      expressing these seven sp-GFP-TMD-CT fusions all exhibited typical punctate
      signals colocalizing with VSR proteins by confocal immunofluorescence. In
      addition, wortmannin caused the GFP-marked prevacuolar organelles to form small
      vacuoles, and VSR antibodies labeled these enlarged MVBs in transgenic BY-2
      cells. Wortmannin also caused VSR-marked PVCs to vacuolate in other cell types,
      including Arabidopsis, rice (Oryza sativa), pea (Pisum sativum), and mung bean
      (Vigna radiata). Therefore, the seven AtVSRs are localized to MVBs in tobacco BY
      2 cells, and wortmannin-induced vacuolation of PVCs is a general response in
      plants.

PMID- 16980566
TI  - Divergence of the Dof gene families in poplar, Arabidopsis, and rice suggests
      multiple modes of gene evolution after duplication.
AB  - It is widely accepted that gene duplication is a primary source of genetic
      novelty. However, the evolutionary fate of duplicated genes remains largely
      unresolved. The classical Ohno's Duplication-Retention-Non/Neofunctionalization
      theory, and the recently proposed alternatives such as subfunctionalization or
      duplication-degeneration-complementation, and subneofunctionalization, each can
      explain one or more aspects of gene fate after duplication. Duplicated genes are
      also affected by epigenetic changes. We constructed a phylogenetic tree using Dof
      (DNA binding with one finger) protein sequences from poplar (Populus trichocarpa)
      Torr. & Gray ex Brayshaw, Arabidopsis (Arabidopsis thaliana), and rice (Oryza
      sativa). From the phylogenetic tree, we identified 27 pairs of paralogous Dof
      genes in the terminal nodes. Analysis of protein motif structure of the Dof
      paralogs and their ancestors revealed six different gene fates after gene
      duplication. Differential protein methylation was revealed between a pair of
      duplicated poplar Dof genes, which have identical motif structure and similar
      expression pattern, indicating that epigenetics is involved in evolution.
      Analysis of reverse transcription-PCR, massively parallel signature sequencing,
      and microarray data revealed that the paralogs differ in expression pattern.
      Furthermore, analysis of nonsynonymous and synonymous substitution rates
      indicated that divergence of the duplicated genes was driven by positive
      selection. About one-half of the motifs in Dof proteins were shared by non-Dof
      proteins in the three plants species, indicating that motif co-option may be one
      of the forces driving gene diversification. We provided evidence that the Ohno's
      Duplication-Retention-Non/Neofunctionalization, subfunctionalization/duplication
      degeneration-complementation, and subneofunctionalization hypotheses are
      complementary with, not alternative to, each other.

PMID- 16980568
TI  - 7-But-2-ynyl-9-(6-methoxy-pyridin-3-yl)-6-piperazin-1-yl-7,9-dihydro-purin-8-one
      is a novel competitive and selective inhibitor of dipeptidyl peptidase IV with an
      antihyperglycemic activity.
AB  - 7-But-2-ynyl-9-(6-methoxy-pyridin-3-yl)-6-piperazin-1-yl-7,9-dihydro-purin-8-one
      (ER-319711) is a novel dipeptidyl peptidase (DPP)-IV inhibitor discovered in our
      laboratories. In this study, we have characterized this DPP-IV inhibitor in vitro
      and in vivo as an antidiabetic agent. The trifluoroacetate salt form of ER
      319711, ER-319711-15, inhibited human DPP-IV with an IC(50) value of 0.089
      microM, whereas its IC(50) values toward human DPP8 and DPP9 were >100 microM.
      Inhibition kinetic pattern analysis indicated that ER-319711-15 inhibited DPP-IV
      in a competitive manner. ER-319711-15 (1 mg/kg) reduced glucose excursion in an
      oral glucose tolerance test (OGTT) using Zucker fa/fa rats, with significant
      increases in plasma insulin and active glucagon-like peptide-1 levels. In an OGTT
      using mice fed a high-fat diet in which ER-319711-15 (0.1-10 mg/kg) was orally
      administered at 0 h, and glucose was loaded at 0 and 5 h, this compound improved
      glucose tolerance dose dependently at both 0- and 5-h glucose loading. Next, we
      compared efficacy of ER-319711-15, E3024, a competitive DPP-IV inhibitor having
      an imidazopyridazinone structure, or vildagliptin, a slow-binding and long-acting
      DPP-IV inhibitor, at the same dose, 10 mg/kg, in the same procedures. At the
      first glucose challenge, all compounds lowered area under the curve (AUC) values
      of delta blood glucose between 0 and 2 h significantly to the same degree. At the
      second glucose load, the AUC values between 5 and 7 h were significantly
      decreased by ER-319711-15 and vildagliptin, but not by E3024. Therefore, ER
      319711 might be a potent, competitive, and selective DPP-IV inhibitor with an
      antihyperglycemic activity.